@article {pmid30697425, year = {2019}, author = {Nesse, RM}, title = {Tinbergen's four questions: Two proximate, two evolutionary.}, journal = {Evolution, medicine, and public health}, volume = {2019}, number = {1}, pages = {2}, doi = {10.1093/emph/eoy035}, pmid = {30697425}, issn = {2050-6201}, } @article {pmid30697424, year = {2019}, author = {Nesse, RM}, title = {The smoke detector principle: Signal detection and optimal defense regulation.}, journal = {Evolution, medicine, and public health}, volume = {2019}, number = {1}, pages = {1}, doi = {10.1093/emph/eoy034}, pmid = {30697424}, issn = {2050-6201}, } @article {pmid30697346, year = {2019}, author = {Brady, SP and Monosson, E and Matson, C and Bickham, JW}, title = {Fundamental and applied pursuits in evolutionary toxicology are mutually beneficial: A reply to Hahn (2018).}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {353}, doi = {10.1111/eva.12710}, pmid = {30697346}, issn = {1752-4571}, } @article {pmid30697345, year = {2019}, author = {Hahn, ME}, title = {Evolutionary concepts can benefit both fundamental research and applied research in toxicology (A comment on Brady et al. 2017).}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {350-352}, doi = {10.1111/eva.12695}, pmid = {30697345}, issn = {1752-4571}, } @article {pmid30697343, year = {2019}, author = {Kim, J and Ni, G and Kim, T and Chun, JY and Kern, EMA and Park, JK}, title = {Phylogeography of the highly invasive sugar beet nematode, Heterodera schachtii (Schmidt, 1871), based on microsatellites.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {324-336}, doi = {10.1111/eva.12719}, pmid = {30697343}, issn = {1752-4571}, abstract = {Plant-parasitic nematodes (PPNs) threaten crop production worldwide. Yet few studies have examined their intraspecific genetic diversity or patterns of invasion, critical data for managing the spread of these cryptic pests. The sugar beet nematode Heterodera schachtii, a global invader that parasitizes over 200 plant species, represents a model for addressing important questions about the invasion genetics of PPNs. Here, a phylogeographic study using 15 microsatellite markers was conducted on 231 H. schachtii individuals sampled from four continents, and invasion history was reconstructed through an approximate Bayesian computation approach, with emphasis on the origin of newly discovered populations in Korea. Multiple analyses confirmed the existence of cryptic lineages within this species, with the Korean populations comprising one group (group 1) and the populations from Europe, Australia, North America, and western Asia comprising another (group 2). No multilocus genotypes were shared between the two groups, and large genetic distance was inferred between them. Population subdivision was also revealed among the populations of group 2 in both population comparison and STRUCTURE analyses, mostly due to different divergent times between invasive and source populations. The Korean populations showed substantial genetic homogeneity and likely originated from a single invasion event. However, none of the other studied populations were implicated as the source. Further studies with additional populations are needed to better describe the distribution of the potential source population for the East Asian lineage.}, } @article {pmid30697342, year = {2019}, author = {Lippens, C and Guivier, E and Reece, SE and O'Donnell, AJ and Cornet, S and Faivre, B and Sorci, G}, title = {Early Plasmodium-induced inflammation does not accelerate aging in mice.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {314-323}, doi = {10.1111/eva.12718}, pmid = {30697342}, issn = {1752-4571}, abstract = {Aging is associated with a decline of performance leading to reduced reproductive output and survival. While the antagonistic pleiotropy theory of aging has attracted considerable attention, the molecular/physiological functions underlying the early-life benefits/late-life costs paradigm remain elusive. We tested the hypothesis that while early activation of the inflammatory response confers benefits in terms of protection against infection, it also incurs costs in terms of reduced reproductive output at old age and shortened longevity. We infected mice with the malaria parasite Plasmodium yoelii and increased the inflammatory response using an anti-IL-10 receptor antibody treatment. We quantified the benefits and costs of the inflammatory response during the acute phase of the infection and at old age. In agreement with the antagonistic pleiotropy hypothesis, the inflammatory response provided an early-life benefit, since infected mice that were treated with anti-IL-10 receptor antibodies had reduced parasite density and anemia. However, at old age, mice in all treatment groups had similar levels of C-reactive protein, reproductive output, survival rate, and lifespan. Overall, our results do not support the hypothesis that the benefits of a robust response to malaria infection in early life incur longer term fitness costs.}, } @article {pmid30697341, year = {2019}, author = {Raynes, Y and Weinreich, DM}, title = {Genomic clustering of fitness-affecting mutations favors the evolution of chromosomal instability.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {301-313}, doi = {10.1111/eva.12717}, pmid = {30697341}, issn = {1752-4571}, abstract = {Most solid cancers are characterized by chromosomal instability (CIN)-an elevated rate of large-scale chromosomal aberrations and ploidy changes. Chromosomal instability may arise through mutations in a range of genomic integrity loci and is commonly associated with fast disease progression, poor prognosis, and multidrug resistance. However, the evolutionary forces promoting CIN-inducing alleles (hereafter, CIN mutators) during carcinogenesis remain poorly understood. Here, we develop a stochastic, individual-based model of indirect selection experienced by CIN mutators via genomic associations with fitness-affecting mutations. Because mutations associated with CIN affect large swaths of the genome and have the potential to simultaneously comprise many individual loci, we show that indirect selection on CIN mutators is critically influenced by genome organization. In particular, we find strong support for a key role played by the spatial clustering of loci with either beneficial or deleterious mutational effects. Genomic clustering of selected loci allows CIN mutators to generate favorable chromosomal changes that facilitate their rapid expansion within a neoplasm and, in turn, accelerate carcinogenesis. We then examine the distribution of oncogenic and tumor-suppressing loci in the human genome and find both to be potentially more clustered along the chromosome than expected, leading us to speculate that human genome may be susceptible to CIN hitchhiking. More quantitative data on fitness effects of individual mutations will be necessary, though, to assess the true levels of clustering in the human genome and the effectiveness of indirect selection for CIN. Finally, we use our model to examine how therapeutic strategies that increase the deleterious burden of genetically unstable cells by raising either the rate of CIN or the cost of deleterious mutations affect CIN evolution. We find that both can inhibit CIN hitchhiking and delay carcinogenesis in some circumstances, yet, in line with earlier work, we find the latter to be considerably more effective.}, } @article {pmid30697340, year = {2019}, author = {Chen, M and Su, G and Fu, J and Wang, A and Liu, JF and Lund, MS and Guldbrandtsen, B}, title = {Introgression of Chinese haplotypes contributed to the improvement of Danish Duroc pigs.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {292-300}, doi = {10.1111/eva.12716}, pmid = {30697340}, issn = {1752-4571}, abstract = {The distribution of Asian ancestry in the genome of Danish Duroc pigs was investigated using whole-genome sequencing data from European wild boars, Danish Duroc, Chinese Meishan and Bamaxiang pigs. Asian haplotypes deriving from Meishan and Bamaxiang occur widely across the genome. Signatures of selection on Asian haplotypes are common in the genome, but few of these haplotypes have been fixed. By defining 50-kb windows with more than 50% Chinese ancestry, which did not exhibit extreme genetic differentiation between Meishan and Bamaxiang as candidate regions, the enrichment of quantitative trait loci in candidate regions supports that Asian haplotypes under selection play an important role in contributing genetic variation underlying production, reproduction, meat and carcass, and exterior traits. Gene annotation of regions with the highest proportion of Chinese ancestry revealed genes of biological interest, such as NR6A1. Further haplotype clustering analysis suggested that a haplotype of Chinese origin around the NR6A1 gene was introduced to Europe and then underwent a selective sweep in European pigs. Besides, functional genes in candidate regions, such as AHR and PGRMC2, associated with fertility, and SAL1, associated with meat quality, were identified. Our results demonstrate the contribution of Asian haplotypes to the genomes of European pigs. Findings herein facilitate further genomic studies such as genomewide association study and genomic prediction by providing ancestry information of variants.}, } @article {pmid30697339, year = {2019}, author = {Grueber, CE and Fox, S and McLennan, EA and Gooley, RM and Pemberton, D and Hogg, CJ and Belov, K}, title = {Complex problems need detailed solutions: Harnessing multiple data types to inform genetic management in the wild.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {280-291}, doi = {10.1111/eva.12715}, pmid = {30697339}, issn = {1752-4571}, abstract = {For bottlenecked populations of threatened species, supplementation often leads to improved population metrics (genetic rescue), provided that guidelines can be followed to avoid negative outcomes. In cases where no "ideal" source populations exist, or there are other complicating factors such as prevailing disease, the benefit of supplementation becomes uncertain. Bringing multiple data and analysis types together to plan genetic management activities can help. Here, we consider three populations of Tasmanian devil, Sarcophilus harrisii, as candidates for genetic rescue. Since 1996, devil populations have been severely impacted by devil facial tumour disease (DFTD), causing significant population decline and fragmentation. Like many threatened species, the key threatening process for devils cannot currently be fully mitigated, so species management requires a multifaceted approach. We examined diversity of 31 putatively neutral and 11 MHC-linked microsatellite loci of three remnant wild devil populations (one sampled at two time-points), alongside computational diversity projections, parameterized by field data from DFTD-present and DFTD-absent sites. Results showed that populations had low diversity, connectivity was poor, and diversity has likely decreased over the last decade. Stochastic simulations projected further diversity losses. For a given population size, the effects of DFTD on population demography (including earlier age at death and increased female productivity) did not impact diversity retention, which was largely driven by final population size. Population sizes ≥500 (depending on the number of founders) were necessary for maintaining diversity in otherwise unmanaged populations, even if DFTD is present. Models indicated that smaller populations could maintain diversity with ongoing immigration. Taken together, our results illustrate how multiple analysis types can be combined to address complex population genetic challenges.}, } @article {pmid30697338, year = {2019}, author = {Nietlisbach, P and Muff, S and Reid, JM and Whitlock, MC and Keller, LF}, title = {Nonequivalent lethal equivalents: Models and inbreeding metrics for unbiased estimation of inbreeding load.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {266-279}, doi = {10.1111/eva.12713}, pmid = {30697338}, issn = {1752-4571}, abstract = {Inbreeding depression, the deterioration in mean trait value in progeny of related parents, is a fundamental quantity in genetics, evolutionary biology, animal and plant breeding, and conservation biology. The magnitude of inbreeding depression can be quantified by the inbreeding load, typically measured in numbers of lethal equivalents, a population genetic quantity that allows for comparisons between environments, populations or species. However, there is as yet no quantitative assessment of which combinations of statistical models and metrics of inbreeding can yield such estimates. Here, we review statistical models that have been used to estimate inbreeding load and use population genetic simulations to investigate how unbiased estimates can be obtained using genomic and pedigree-based metrics of inbreeding. We use simulated binary viability data (i.e., dead versus alive) as our example, but the concepts apply to any trait that exhibits inbreeding depression. We show that the increasingly popular generalized linear models with logit link do not provide comparable and unbiased population genetic measures of inbreeding load, independent of the metric of inbreeding used. Runs of homozygosity result in unbiased estimates of inbreeding load, whereas inbreeding measured from pedigrees results in slight overestimates. Due to widespread use of models that do not yield unbiased measures of the inbreeding load, some estimates in the literature cannot be compared meaningfully. We surveyed the literature for reliable estimates of the mean inbreeding load from wild vertebrate populations and found an average of 3.5 haploid lethal equivalents for survival to sexual maturity. To obtain comparable estimates, we encourage researchers to use generalized linear models with logarithmic links or maximum-likelihood estimation of the exponential equation, and inbreeding coefficients calculated from runs of homozygosity, provided an assembled reference genome of sufficient quality and enough genetic marker data are available.}, } @article {pmid30697337, year = {2019}, author = {Crandall, ED and Toonen, RJ and , and Selkoe, KA}, title = {A coalescent sampler successfully detects biologically meaningful population structure overlooked by F-statistics.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {255-265}, doi = {10.1111/eva.12712}, pmid = {30697337}, issn = {1752-4571}, abstract = {Assessing the geographic structure of populations has relied heavily on Sewell Wright's F-statistics and their numerous analogues for many decades. However, it is well appreciated that, due to their nonlinear relationship with gene flow, F-statistics frequently fail to reject the null model of panmixia in species with relatively high levels of gene flow and large population sizes. Coalescent genealogy samplers instead allow a model-selection approach to the characterization of population structure, thereby providing the opportunity for stronger inference. Here, we validate the use of coalescent samplers in a high gene flow context using simulations of a stepping-stone model. In an example case study, we then re-analyze genetic datasets from 41 marine species sampled from throughout the Hawaiian archipelago using coalescent model selection. Due to the archipelago's linear nature, it is expected that most species will conform to some sort of stepping-stone model (leading to an expected pattern of isolation by distance), but F-statistics have only supported this inference in ~10% of these datasets. Our simulation analysis shows that a coalescent sampler can make a correct inference of stepping-stone gene flow in nearly 100% of cases where gene flow is ≤100 migrants per generation (equivalent to FST = 0.002), while F-statistics had mixed results. Our re-analysis of empirical datasets found that nearly 70% of datasets with an unambiguous result fit a stepping-stone model with varying population sizes and rates of gene flow, although 37% of datasets yielded ambiguous results. Together, our results demonstrate that coalescent samplers hold great promise for detecting weak but meaningful population structure, and defining appropriate management units.}, } @article {pmid30697336, year = {2019}, author = {Beacham, TD and Wallace, C and Jonsen, K and McIntosh, B and Candy, JR and Willis, D and Lynch, C and Moore, JS and Bernatchez, L and Withler, RE}, title = {Comparison of coded-wire tagging with parentage-based tagging and genetic stock identification in a large-scale coho salmon fisheries application in British Columbia, Canada.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {230-254}, doi = {10.1111/eva.12711}, pmid = {30697336}, issn = {1752-4571}, abstract = {Wild Pacific salmon, including Coho salmon Onchorynchus kisutch, have been supplemented with hatchery propagation for over 50 years in support of increased ocean harvest and conservation of threatened populations. In Canada, the Wild Salmon Policy for Pacific salmon was established with the goal of maintaining and restoring healthy and diverse Pacific salmon populations, making conservation of wild salmon and their habitats the highest priority for resource management decision-making. A new approach to the assessment and management of wild coho salmon, and the associated hatchery production and fishery management is needed. Implementation of parentage-based tagging (PBT) may overcome problems associated with coded-wire tag-based (CWT) assessment and management of coho salmon fisheries, providing at a minimum information equivalent to that derived from the CWT program. PBT and genetic stock identification (GSI) were used to identify coho salmon sampled in fisheries (8,006 individuals) and escapements (1,692 individuals) in British Columbia to specific conservation units (CU), populations, and broodyears. Individuals were genotyped at 304 single nucleotide polymorphisms (SNPs) via direct sequencing of amplicons. Very high accuracy of assignment to population (100%) via PBT for 543 jack (age 2) assigned to correct age and collection location and 265 coded-wire tag (CWT, age 3) coho salmon assigned to correct age and release location was observed, with a 40,774-individual, 267-population baseline available for assignment. Coho salmon from un-CWTed enhanced populations contributed 65% of the catch in southern recreational fisheries in 2017. Application of a PBT-GSI system of identification to individuals in 2017 fisheries and escapements provided high-resolution estimates of stock composition, catch, and exploitation rate by CU or population, providing an alternate and more effective method in the assessment and management of Canadian-origin coho salmon relative to CWTs, and an opportunity for a genetic-based system to replace the current CWT system for coho salmon assessment.}, } @article {pmid30697335, year = {2019}, author = {DeFilippo, LB and Schindler, DE and Ohlberger, J and Schaberg, KL and Foster, MB and Ruhl, D and Punt, AE}, title = {Recruitment variation disrupts the stability of alternative life histories in an exploited salmon population.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {214-229}, doi = {10.1111/eva.12709}, pmid = {30697335}, issn = {1752-4571}, abstract = {Males of many fish species exhibit alternative reproductive tactics, which can influence the maturation schedules, fishery productivity, and resilience to harvest of exploited populations. While alternative mating phenotypes can persist in stable equilibria through frequency-dependent selection, shifts in tactic frequencies have been observed and can have substantial consequences for fisheries. Here, we examine the dynamics of precocious sneaker males called "jacks" in a population of sockeye salmon (Oncorhynchus nerka) from Frazer Lake, Alaska. Jacks, which are of little commercial value due to their small body sizes, have recently been observed at unusually high levels in this stock, degrading the value of regional fisheries. To inform future strategies for managing the prevalence of jacks, we used long-term monitoring data to identify what regulates the frequencies of alternative male phenotypes in the population over time. Expression of the jack life history could not be explained by environmental factors expected to influence juvenile body condition and maturation probability. Instead, we found a strong positive association between the proportion of individuals maturing as jacks within a cohort and the prevalence of jacks among the males that sired that cohort. Moreover, due to differences in age-at-maturity between male phenotypes, and large interannual variability in recruitment strength, jacks from strong year-classes often spawn among older males from the weaker recruitments of earlier cohorts. Through such "cohort mismatches," which are amplified by size-selective harvest on older males, jacks frequently achieve substantial representation in the breeding population, and likely high total fertilizations. The repeated occurrence of these cohort mismatches appears to disrupt the stabilizing influence of frequency-dependent selection, allowing the prevalence of jacks to exceed what might be expected under equilibrium conditions. These results emphasize that the dynamics of alternative life histories can profoundly influence fishery performance and should be explicitly considered in the management of exploited populations.}, } @article {pmid30697334, year = {2019}, author = {Jahner, JP and Matocq, MD and Malaney, JL and Cox, M and Wolff, P and Gritts, MA and Parchman, TL}, title = {The genetic legacy of 50 years of desert bighorn sheep translocations.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {198-213}, doi = {10.1111/eva.12708}, pmid = {30697334}, issn = {1752-4571}, abstract = {Conservation biologists have increasingly used translocations to mitigate population declines and restore locally extirpated populations. Genetic data can guide the selection of source populations for translocations and help evaluate restoration success. Bighorn sheep (Ovis canadensis) are a managed big game species that suffered widespread population extirpations across western North America throughout the early 1900s. Subsequent translocation programs have successfully re-established many formally extirpated bighorn herds, but most of these programs pre-date genetically informed management practices. The state of Nevada presents a particularly well-documented case of decline followed by restoration of extirpated herds. Desert bighorn sheep (O. c. nelsoni) populations declined to less than 3,000 individuals restricted to remnant herds in the Mojave Desert and a few locations in the Great Basin Desert. Beginning in 1968, the Nevada Department of Wildlife translocated ~2,000 individuals from remnant populations to restore previously extirpated areas, possibly establishing herds with mixed ancestries. Here, we examined genetic diversity and structure among remnant herds and the genetic consequences of translocation from these herds using a genotyping-by-sequencing approach to genotype 17,095 loci in 303 desert bighorn sheep. We found a signal of population genetic structure among remnant Mojave Desert populations, even across geographically proximate mountain ranges. Further, we found evidence of a genetically distinct, potential relict herd from a previously hypothesized Great Basin lineage of desert bighorn sheep. The genetic structure of source herds was clearly reflected in translocated populations. In most cases, herds retained genetic evidence of multiple translocation events and subsequent admixture when founded from multiple remnant source herds. Our results add to a growing literature on how population genomic data can be used to guide and monitor restoration programs.}, } @article {pmid30697333, year = {2019}, author = {Gous, A and Swanevelder, DZH and Eardley, CD and Willows-Munro, S}, title = {Plant-pollinator interactions over time: Pollen metabarcoding from bees in a historic collection.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {187-197}, doi = {10.1111/eva.12707}, pmid = {30697333}, issn = {1752-4571}, abstract = {Pollination is a key component in agricultural food production and ecosystem maintenance, with plant-pollinator interactions an important research theme in ecological and evolutionary studies. Natural history collections provide unique access to samples collected at different spatial and temporal scales. Identification of the plant origins of pollen trapped on the bodies of pollinators in these collections provides insight into historic plant communities and pollinators' preferred floral taxa. In this study, pollen was sampled from Megachile venusta Smith bees from the National Collection of Insects, South Africa, spanning 93 years. Three barcode regions, the internal transcribed spacer 1 and 2 (ITS1 and ITS2) and ribulose-1,5-biphosphate carboxylase (rbcL), were sequenced from mixed pollen samples using a next-generation sequencing approach (MiSeq, Illumina). Sequenced reads were compared to sequence reference databases that were generated by extracting sequence and taxonomic data from GenBank. ITS1 and ITS2 were amplified successfully across all (or most) samples, while rbcL performed inconsistently. Age of sample had no impact on sequencing success. Plant classification was more informative using ITS2 than ITS1 barcode data. This study also highlights the need for comprehensive reference databases as limited local plant sequence representation in reference databases resulted in higher-level taxon classifications being more confidently interpreted. The results showed that small, insect-carried pollen samples from historic bee specimens collected from as early as 1914 can be used to obtain pollen metabarcodes. DNA metabarcoding of mixed origin pollen samples provided a faster, more accurate method of determining pollen provenance, without the need for expert palynologists. The use of historic collections to sample pollen directly from pollinators provided additional value to these collections. Sampling pollen from historic collections can potentially provide the spatial and temporal scales for investigations into changes in plant community structure or pollinator floral choice in the face of global climate change.}, } @article {pmid30697332, year = {2019}, author = {Robertson, BA and Horváth, G}, title = {Color polarization vision mediates the strength of an evolutionary trap.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {175-186}, doi = {10.1111/eva.12690}, pmid = {30697332}, issn = {1752-4571}, abstract = {Evolutionary traps are scenarios in which animals are fooled by rapidly changing conditions into preferring poor-quality resources over those that better improve survival and reproductive success. The maladaptive attraction of aquatic insects to artificial sources of horizontally polarized light (e.g., glass buildings, asphalt roads) has become a first model system by which scientists can investigate the behavioral mechanisms that cause traps to occur. We employ this field-based system to experimentally investigate (a) in which portion(s) of the spectrum are polarizationally water-imitating reflectors attractive to nocturnal terrestrial and aquatics insects, and (b) which modern lamp types result in greater attraction in this typical kind of nocturnal polarized light pollution. We found that most aquatic taxa exhibited preferences for lamps based upon their color spectra, most having lowest preference for lamps emitting blue and red light. Yet, despite previously established preference for higher degrees of polarization of reflected light, most aquatic insect families were attracted to traps based upon their unpolarized spectrum. Chironomid midges, alone, showed a preference for the color of lamplight in both the horizontally polarized and unpolarized spectra indicating only this family has evolved to use light in this color range as a source of information to guide its nocturnal habitat selection. These results demonstrate that the color of artificial lighting can exacerbate or reduce its attractiveness to aquatic insects, but that the strength of attractiveness of nocturnal evolutionary traps, and so their demographic consequences, is primarily driven by unpolarized light pollution. This focuses management attention on limiting broad-spectrum light pollution, as well as its intentional deployment to attract insects back to natural habitats.}, } @article {pmid30697331, year = {2019}, author = {Warwell, MV and Shaw, RG}, title = {Phenotypic selection on ponderosa pine seed and seedling traits in the field under three experimentally manipulated drought treatments.}, journal = {Evolutionary applications}, volume = {12}, number = {2}, pages = {159-174}, doi = {10.1111/eva.12685}, pmid = {30697331}, issn = {1752-4571}, abstract = {Drought-related selection during seedling emergence and early development may play a strong role in adaptation. Yet this process is poorly understood and particularly so in relation to ongoing climate change. To evaluate drought-induced differences in selection during early life stages, a total of 50 maternal families sampled from three climatically disparate ponderosa pine (Pinus ponderosa Doug.) populations were grown from seed in two common garden field experiments at a location that was warmer and drier than seed origins. Three drought treatments were imposed experimentally. Phenotypic selection was assessed by relating plant fitness measured as survival or unconditional expected height at age 3 to seed density (mass per unit volume), date of emergence, and timing of shoot elongation. In the year of emergence from seed, differential mortality was particularly strong and clearly indicated selection. In contrast, selection in subsequent years was far less pronounced. Phenotypes with high seed density, an intermediate but relatively early emergence date, and high 2nd-year early-season shoot elongation exhibited the greatest estimated fitness under drought. The form of selection varied among seed sources in relation to drought treatment. Selection was generally more acute in the cases of greatest difference between drought treatment and climatic patterns of precipitation at the site of seed origin. These results suggest that populations of ponderosa pine are differentially adapted to drought patterns associated with the climate of their origin. To the extent that the phenotypic traits examined are heritable or correlated with heritable traits, our results provide insight into how tree populations may evolve in response to drought.}, } @article {pmid30693638, year = {2018}, author = {Togawa, M and Endo, Y and Suzuki, N and Yokoi, H and Suzuki, T}, title = {Identification of Sox10-positive cells at the dorsal fin base of juvenile flounder that are correlated with blind-side skin ectopic pigmentation.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {8}, pages = {427-437}, doi = {10.1002/jez.b.22842}, pmid = {30693638}, issn = {1552-5015}, support = {18K05813//JSPS KAKENHI/ ; 15KK0272//JSPS KAKENHI/ ; 17H03867//JSPS KAKENHI/ ; 16K07871//JSPS KAKENHI/ ; }, abstract = {Flounder develop left-right asymmetric body color, with a dark ocular side and white blind side. However, ectopic pigmentation often occurs on the blind side when juveniles are reared in tanks. To examine the developmental mechanism underlying ectopic pigmentation, we first examined the pigmentation process on the blind side and the localization of chromatoblasts during spontaneous and regeneration-stimulated ectopic pigmentation. Wild-caught juveniles that had completed metamorphosis in a natural environment were reared in tanks, where they exhibited ectopic pigmentation on the blind side that was initiated at the base of the dorsal and anal fins, with chromatoblasts appearing at the edges of scales and melanophores spreading on the scale papilla beneath the epidermis. During tissue regeneration at the base of the dorsal fin in juvenile before ectopic pigmentation, melanophores and chromatoblasts newly appeared on regenerated blind-side skin, resulting in rapid pigmentation at the wounded site. During regeneration-stimulated pigmentation, gch2-positive chromatoblasts were detected only under the regenerated epidermis. Next, we found that Sox10-positive cells were localized in connective tissue at the base of the dorsal fin and that when connective tissue was labeled with DiO, DiO-labeled melanophores appeared in regenerated skin of the blind side after wounding. Therefore, we conclude that in flounder juveniles, Sox10-positive progenitors of pigment cell lineage reside at the base of the dorsal fin and start migrating to the blind-side skin in response to specific stimuli, resulting in ectopic pigmentation. Ectopic pigmentation in flounder could be a good model for examining the flexibility of pigment cell differentiation.}, } @article {pmid30680854, year = {2018}, author = {Yücel, O and Borgert, SR and Poehlein, A and Niermann, K and Philipp, B}, title = {The 7α-hydroxysteroid dehydratase Hsh2 is essential for anaerobic degradation of the steroid skeleton of 7α-hydroxyl bile salts in the novel denitrifying bacterium Azoarcus sp. strain Aa7.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14508}, pmid = {30680854}, issn = {1462-2920}, support = {INST 211/646-1 FUGG//Deutsche Forschungsgemeinschaft/ ; PH71/3-2//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Bile salts are steroid compounds from the digestive tract of vertebrates and enter the environment via defecation. Many aerobic bile-salt degrading bacteria are known but no bacteria that completely degrade bile salts under anoxic conditions have been isolated so far. In this study, the facultatively anaerobic Betaproteobacterium Azoarcus sp. strain Aa7 was isolated that grew with bile salts as sole carbon source under anoxic conditions with nitrate as electron acceptor. Phenotypic and genomic characterization revealed that strain Aa7 used the 2,3-seco pathway for the degradation of bile salts as found in other denitrifying steroid-degrading bacteria such as Sterolibacterium denitrificans. Under oxic conditions strain Aa7 used the 9,10-seco pathway as found in, for example, Pseudomonas stutzeri Chol1. Metabolite analysis during anaerobic growth indicated a reductive dehydroxylation of 7α-hydroxyl bile salts. Deletion of the gene hsh2 Aa7 encoding a 7-hydroxysteroid dehydratase led to strongly impaired growth with cholate and chenodeoxycholate but not with deoxycholate lacking a hydroxyl group at C7. The hsh2 Aa7 deletion mutant degraded cholate and chenodeoxycholate to the corresponding C19 -androstadienediones only while no phenotype change was observed during aerobic degradation of cholate. These results showed that removal of the 7α-hydroxyl group was essential for cleavage of the steroid skeleton under anoxic conditions.}, } @article {pmid30680151, year = {2019}, author = {Ferrier-Pagès, C and Leal, MC}, title = {Stable isotopes as tracers of trophic interactions in marine mutualistic symbioses.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {723-740}, doi = {10.1002/ece3.4712}, pmid = {30680151}, issn = {2045-7758}, abstract = {Mutualistic nutritional symbioses are widespread in marine ecosystems. They involve the association of a host organism (algae, protists, or marine invertebrates) with symbiotic microorganisms, such as bacteria, cyanobacteria, or dinoflagellates. Nutritional interactions between the partners are difficult to identify in symbioses because they only occur in intact associations. Stable isotope analysis (SIA) has proven to be a useful tool to highlight original nutrient sources and to trace nutrients acquired by and exchanged between the different partners of the association. However, although SIA has been extensively applied to study different marine symbiotic associations, there is no review taking into account of the different types of symbiotic associations, how they have been studied via SIA, methodological issues common among symbiotic associations, and solutions that can be transferred from one type of association with another. The present review aims to fill such gaps in the scientific literature by summarizing the current knowledge of how isotopes have been applied to key marine symbioses to unravel nutrient exchanges between partners, and by describing the difficulties in interpreting the isotopic signal. This review also focuses on the use of compound-specific stable isotope analysis and on statistical advances to analyze stable isotope data. It also highlights the knowledge gaps that would benefit from future research.}, } @article {pmid30680150, year = {2019}, author = {Arias-Martorell, J}, title = {The morphology and evolutionary history of the glenohumeral joint of hominoids: A review.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {703-722}, doi = {10.1002/ece3.4392}, pmid = {30680150}, issn = {2045-7758}, abstract = {The glenohumeral joint, the most mobile joint in the body of hominoids, is involved in the locomotion of all extant primates apart from humans. Over the last few decades, our knowledge of how variation in its morphological characteristics relates to different locomotor behaviors within extant primates has greatly improved, including features of the proximal humerus and the glenoid cavity of the scapula, as well as the muscles that function to move the joint (the rotator cuff muscles). The glenohumeral joint is a region with a strong morphofunctional signal, and hence, its study can shed light on the locomotor behaviors of crucial ancestral nodes in the evolutionary history of hominoids (e.g., the last common ancestor between humans and chimpanzees). Hominoids, in particular, are distinct in showing round and relatively big proximal humeri with lowered tubercles and flattened and oval glenoid cavities, morphology suited to engage in a wide range of motions, which enables the use of locomotor behaviors such as suspension. The comparison with extant taxa has enabled more informed functional interpretations of morphology in extinct primates, including hominoids, from the Early Miocene through to the emergence of hominins. Here, I review our current understanding of glenohumeral joint functional morphology and its evolution throughout the Miocene and Pleistocene, as well as highlighting the areas where a deeper study of this joint is still needed.}, } @article {pmid30680149, year = {2019}, author = {Fresneau, N and Müller, W}, title = {Flexible communication within bird families-The consequences of behavioral plasticity for parent-offspring coadaptation.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {693-702}, doi = {10.1002/ece3.4796}, pmid = {30680149}, issn = {2045-7758}, abstract = {Offspring are selected to demand more resources than what is optimal for their parents to provide, which results in a complex and dynamic interplay during parental care. Parent-offspring communication often involves conspicuous begging by the offspring which triggers a parental response, typically the transfer of food. So begging and parental provisioning reciprocally influence each other and are therefore expected to coevolve. There is indeed empirical evidence for covariation of offspring begging and parental provisioning at the phenotypic level. However, whether this reflects genetic correlations of mean levels of behaviors or a covariation of the slopes of offspring demand and parental supply functions (= behavioral plasticity) is not known. The latter has gone rather unnoticed-despite the obvious dynamics of parent-offspring communication. In this study, we measured parental provisioning and begging behavior at two different hunger levels using canaries (Serinus canaria) as a model species. This enabled us to simultaneously study the plastic responses of the parents and the offspring to changes in offspring need. We first tested whether parent and offspring behaviors covary phenotypically. Then, using a covariance partitioning approach, we estimated whether the covariance predominantly occurred at a between-nest level (i.e., indicating a fixed strategy) or at a within-nest level (i.e., reflecting a flexible strategy). We found positive phenotypic covariation of offspring begging and parental provisioning, confirming previous evidence. Yet, this phenotypic covariation was mainly driven by a covariance at the within-nest level. That is parental and offspring behaviors covary because of a plastic behavioral coadjustment, indicating that behavioral plasticity could be a main driver of parent-offspring coadaptation.}, } @article {pmid30680148, year = {2019}, author = {Hill, JM and Renfrew, RB}, title = {Migratory patterns and connectivity of two North American grassland bird species.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {680-692}, doi = {10.1002/ece3.4795}, pmid = {30680148}, issn = {2045-7758}, abstract = {Effective management and conservation of migratory bird populations require knowledge and incorporation of their movement patterns and space use throughout the annual cycle. To investigate the little-known migratory patterns of two grassland bird species, we deployed 180 light-level geolocators on Grasshopper Sparrows (Ammodramus savannarum) and 29 Argos-GPS tags on Eastern Meadowlarks (Sturnella magna) at Konza Prairie, Kansas, USA, and six US Department of Defense (DoD) installations distributed across the species' breeding ranges. We analyzed location data from 34 light-level geolocators and five Argos-GPS tags attached for 1 year to Grasshopper Sparrows and Eastern Meadowlarks, respectively. Grasshopper Sparrows were present on the breeding grounds from mid-April through early October, substantially longer than previously estimated, and migrated on average ~2,500 km over ~30 days. Grasshopper Sparrows exhibited strong migratory connectivity only at a continental scale. The North American Great Lakes region likely serves as a migratory divide for Midwest and East Coast Grasshopper Sparrows; Midwest populations (Kansas, Wisconsin, and North Dakota; n = 13) largely wintered in Texas or Mexico, whereas East Coast populations (Maryland and Massachusetts, n = 20) wintered in the northern Caribbean or Florida. Our data from Eastern Meadowlarks provided evidence for a diversity of stationary and short- and long-distance migration strategies. By providing the most extensive examination of the nonbreeding movement ecology for these two North American grassland bird species to date, we refine information gaps and provide key insight for their management and conservation.}, } @article {pmid30680147, year = {2019}, author = {Barthel, LMF and Hofer, H and Berger, A}, title = {An easy, flexible solution to attach devices to hedgehogs (Erinaceus europaeus) enables long-term high-resolution studies.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {672-679}, doi = {10.1002/ece3.4794}, pmid = {30680147}, issn = {2045-7758}, abstract = {Bio-logging is an essential tool for the investigation of behavior, ecology, and physiology of wildlife. This burgeoning field enables the improvement of population monitoring and conservation efforts, particularly for small, elusive animals where data collection is difficult. Device attachment usually requires species-specific solutions to ensure that data loggers exert minimal influence on the animal's behavior and physiology, and ensure high reliability of data capture. External features or peculiar body shapes often make securing devices difficult for long-term monitoring, as in the case with small spiny mammals. Here, we present a method that enables high-resolution, long-term investigations of European hedgehogs (Erinaceus europaeus) via GPS and acceleration loggers. We collected data from 17 wild hedgehogs with devices attached between 9 and 42 days. Our results showed that hedgehogs behaved naturally; as individuals curled, moved through dense vegetation, slipped under fences and built regular day nests without any indication of impediment. Our novel method makes it possible to not only attach high-precision devices for substantially longer than previous efforts, but enables detachment and reattachment of devices to the same individual. This makes it possible to quickly respond to unforeseen events and exchange devices, and overcomes the issue of short battery life common to many lightweight loggers.}, } @article {pmid30680146, year = {2019}, author = {Reisch, C and Schmid, C}, title = {Species and genetic diversity are not congruent in fragmented dry grasslands.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {664-671}, doi = {10.1002/ece3.4791}, pmid = {30680146}, issn = {2045-7758}, abstract = {Biological diversity comprises both species diversity (SD) and genetic diversity (GD), and it has been postulated that both levels of diversity depend on similar mechanisms. Species-genetic diversity correlations (SGDC) are therefore supposed to be generally positive. However, in contrast to theory, empirical data are contradictory. Furthermore, there is a pronounced lack of multispecies studies including also the ecological factors potentially driving species and genetic diversity. We analyzed the relationship between the species diversity of dry grasslands and the genetic diversity of several dry grassland plant species, therefore, in the context of habitat fragmentation and habitat conditions. Our study revealed a lack of correlation between species and genetic diversity. We demonstrated previously that SD mainly depends on habitat conditions (vegetation height and cover of litter), whereas GD is significantly affected by habitat fragmentation (distance to the nearest dry grassland in 1830 and connectivity in 2013). This seems to be the main reason why SD and GD are not congruent in fragmented grasslands. Our results support, hence, the observation that positive SGDCs can mainly be found in natural, island-like study systems in equilibrium and at similar levels of heterogeneity. In fragmented dry grassland ecosystems, which differ in heterogeneity, this state of equilibrium may not have been reached mitigating the positive relationship between SD and GD. From our study, it can be concluded that in fragmented dry grasslands, the protection of SD does not necessarily ensure the conservation of GD.}, } @article {pmid30680145, year = {2019}, author = {Pennino, MG and Paradinas, I and Illian, JB and Muñoz, F and Bellido, JM and López-Quílez, A and Conesa, D}, title = {Accounting for preferential sampling in species distribution models.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {653-663}, doi = {10.1002/ece3.4789}, pmid = {30680145}, issn = {2045-7758}, abstract = {Species distribution models (SDMs) are now being widely used in ecology for management and conservation purposes across terrestrial, freshwater, and marine realms. The increasing interest in SDMs has drawn the attention of ecologists to spatial models and, in particular, to geostatistical models, which are used to associate observations of species occurrence or abundance with environmental covariates in a finite number of locations in order to predict where (and how much of) a species is likely to be present in unsampled locations. Standard geostatistical methodology assumes that the choice of sampling locations is independent of the values of the variable of interest. However, in natural environments, due to practical limitations related to time and financial constraints, this theoretical assumption is often violated. In fact, data commonly derive from opportunistic sampling (e.g., whale or bird watching), in which observers tend to look for a specific species in areas where they expect to find it. These are examples of what is referred to as preferential sampling, which can lead to biased predictions of the distribution of the species. The aim of this study is to discuss a SDM that addresses this problem and that it is more computationally efficient than existing MCMC methods. From a statistical point of view, we interpret the data as a marked point pattern, where the sampling locations form a point pattern and the measurements taken in those locations (i.e., species abundance or occurrence) are the associated marks. Inference and prediction of species distribution is performed using a Bayesian approach, and integrated nested Laplace approximation (INLA) methodology and software are used for model fitting to minimize the computational burden. We show that abundance is highly overestimated at low abundance locations when preferential sampling effects not accounted for, in both a simulated example and a practical application using fishery data. This highlights that ecologists should be aware of the potential bias resulting from preferential sampling and account for it in a model when a survey is based on non-randomized and/or non-systematic sampling.}, } @article {pmid30680144, year = {2019}, author = {Beaugeard, E and Brischoux, F and Henry, PY and Parenteau, C and Trouvé, C and Angelier, F}, title = {Does urbanization cause stress in wild birds during development? Insights from feather corticosterone levels in juvenile house sparrows (Passer domesticus).}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {640-652}, doi = {10.1002/ece3.4788}, pmid = {30680144}, issn = {2045-7758}, abstract = {Urban landscapes are associated with abiotic and biotic environmental changes that may result in potential stressors for wild vertebrates. Urban exploiters have physiological, morphological, and behavioral adaptations to live in cities. However, there is increasing evidence that urban exploiters themselves can suffer from urban conditions, especially during specific life-history stages. We looked for a link between the degree of urbanization and the level of developmental stress in an urban exploiter (the house sparrow, Passer domesticus), which has recently been declining in multiple European cities (e.g., London, UK). Specifically, we conducted a large-scale study and sampled juvenile sparrows in 11 urban and rural sites to evaluate their feather corticosterone (CORT) levels. We found that juvenile feather CORT levels were positively correlated with the degree of urbanization, supporting the idea that developing house sparrows may suffer from urban environmental conditions. However, we did not find any correlation between juvenile feather CORT levels and body size, mass, or body condition. This suggests either that the growth and condition of urban sparrows are not impacted by elevated developmental CORT levels, or that urban sparrows may compensate for developmental constraints once they have left the nest. Although feather CORT levels were not correlated with baseline CORT levels, we found that feather CORT levels were slightly and positively correlated with the CORT stress response in juveniles. This suggests that urban developmental conditions may potentially have long-lasting effects on stress physiology and stress sensitivity in this urban exploiter.}, } @article {pmid30680143, year = {2019}, author = {Rytkönen, S and Vesterinen, EJ and Westerduin, C and Leviäkangas, T and Vatka, E and Mutanen, M and Välimäki, P and Hukkanen, M and Suokas, M and Orell, M}, title = {From feces to data: A metabarcoding method for analyzing consumed and available prey in a bird-insect food web.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {631-639}, doi = {10.1002/ece3.4787}, pmid = {30680143}, issn = {2045-7758}, abstract = {Diets play a key role in understanding trophic interactions. Knowing the actual structure of food webs contributes greatly to our understanding of biodiversity and ecosystem functioning. The research of prey preferences of different predators requires knowledge not only of the prey consumed, but also of what is available. In this study, we applied DNA metabarcoding to analyze the diet of 4 bird species (willow tits Poecile montanus, Siberian tits Poecile cinctus, great tits Parus major and blue tits Cyanistes caeruleus) by using the feces of nestlings. The availability of their assumed prey (Lepidoptera) was determined from feces of larvae (frass) collected from the main foraging habitat, birch (Betula spp.) canopy. We identified 53 prey species from the nestling feces, of which 11 (21%) were also detected from the frass samples (eight lepidopterans). Approximately 80% of identified prey species in the nestling feces represented lepidopterans, which is in line with the earlier studies on the parids' diet. A subsequent laboratory experiment showed a threshold for fecal sample size and the barcoding success, suggesting that the smallest frass samples do not contain enough larval DNA to be detected by high-throughput sequencing. To summarize, we apply metabarcoding for the first time in a combined approach to identify available prey (through frass) and consumed prey (via nestling feces), expanding the scope and precision for future dietary studies on insectivorous birds.}, } @article {pmid30680142, year = {2019}, author = {Studd, EK and Landry-Cuerrier, M and Menzies, AK and Boutin, S and McAdam, AG and Lane, JE and Humphries, MM}, title = {Behavioral classification of low-frequency acceleration and temperature data from a free-ranging small mammal.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {619-630}, doi = {10.1002/ece3.4786}, pmid = {30680142}, issn = {2045-7758}, abstract = {The miniaturization and affordability of new technology is driving a biologging revolution in wildlife ecology with use of animal-borne data logging devices. Among many new biologging technologies, accelerometers are emerging as key tools for continuously recording animal behavior. Yet a critical, but under-acknowledged consideration in biologging is the trade-off between sampling rate and sampling duration, created by battery- (or memory-) related sampling constraints. This is especially acute among small animals, causing most researchers to sample at high rates for very limited durations. Here, we show that high accuracy in behavioral classification is achievable when pairing low-frequency acceleration recordings with temperature. We conducted 84 hr of direct behavioral observations on 67 free-ranging red squirrels (200-300 g) that were fitted with accelerometers (2 g) recording tri-axial acceleration and temperature at 1 Hz. We then used a random forest algorithm and a manually created decision tree, with variable sampling window lengths, to associate observed behavior with logger recorded acceleration and temperature. Finally, we assessed the accuracy of these different classifications using an additional 60 hr of behavioral observations, not used in the initial classification. The accuracy of the manually created decision tree classification using observational data varied from 70.6% to 91.6% depending on the complexity of the tree, with increasing accuracy as complexity decreased. Short duration behavior like running had lower accuracy than long-duration behavior like feeding. The random forest algorithm offered similarly high overall accuracy, but the manual decision tree afforded the flexibility to create a hierarchical tree, and to adjust sampling window length for behavioral states with varying durations. Low frequency biologging of acceleration and temperature allows accurate behavioral classification of small animals over multi-month sampling durations. Nevertheless, low sampling rates impose several important limitations, especially related to assessing the classification accuracy of short duration behavior.}, } @article {pmid30680141, year = {2019}, author = {Knapp, JL and Becher, MA and Rankin, CC and Twiston-Davies, G and Osborne, JL}, title = {Bombus terrestris in a mass-flowering pollinator-dependent crop: A mutualistic relationship?.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {609-618}, doi = {10.1002/ece3.4784}, pmid = {30680141}, issn = {2045-7758}, abstract = {Bumblebees (Bombus spp.) rely on an abundant and diverse selection of floral resources to meet their nutritional requirements. In farmed landscapes, mass-flowering crops can provide an important forage resource for bumblebees, with increased visitation from bumblebees into mass-flowering crops having an additional benefit to growers who require pollination services. This study explores the mutualistic relationship between Bombus terrestris L. (buff-tailed bumblebee), a common species in European farmland, and the mass-flowering crop courgette (Cucurbita pepo L.) to see how effective B. terrestris is at pollinating courgette and in return how courgette may affect B. terrestris colony dynamics. By combining empirical data on nectar and pollen availability with model simulations using the novel bumblebee model Bumble-BEEHAVE, we were able to quantify and simulate for the first time, the importance of courgette as a mass-flowering forage resource for bumblebees. Courgette provides vast quantities of nectar to ensure a high visitation rate, which combined with abundant pollen grains, enables B. terrestris to have a high pollination potential. While B. terrestris showed a strong fidelity to courgette flowers for nectar, courgette pollen was not found in any pollen loads from returning foragers. Nonetheless, model simulations showed that early season courgette (nectar) increased the number of hibernating queens, colonies, and adult workers in the modeled landscapes. Synthesis and applications. Courgette has the potential to improve bumblebee population dynamics; however, the lack of evidence of the bees collecting courgette pollen in this study suggests that bees can only benefit from this transient nectar source if alternative floral resources, particularly pollen, are also available to fulfill bees' nutritional requirements in space and time. Therefore, providing additional forage resources could simultaneously improve pollination services and bumblebee populations.}, } @article {pmid30680140, year = {2019}, author = {Trubitt, RT and Hovick, TJ and Gillam, EH and McGranahan, DA}, title = {Habitat associations of bats in a working rangeland landscape.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {598-608}, doi = {10.1002/ece3.4782}, pmid = {30680140}, issn = {2045-7758}, abstract = {Land-use change has resulted in rangeland loss and degradation globally. These changes include conversion of native grasslands for row-crop agriculture as well as degradation of remaining rangeland due to fragmentation and changing disturbance regimes. Understanding how these and other factors influence wildlife use of rangelands is important for conservation and management of wildlife populations. We investigated bat habitat associations in a working rangeland in southeastern North Dakota. We used Petterson d500x acoustic detectors to systematically sample bat activity across the study area on a 1-km point grid. We identified calls using Sonobat autoclassification software. We detected five species using this working rangeland, which included Lasionycteris noctivagans (2,722 detections), Lasiurus cinereus (2,055 detections), Eptesicus fuscus (749 detections), Lasiurusborealis (62 detections), and Myotis lucifugus (1 detection). We developed generalized linear mixed-effects models for the four most frequently detected species based on their ecology. The activity of three bat species increased with higher tree cover. While the scale of selection varied between the four species, all three investigated scales were explanatory for at least one bat species. The broad importance of trees to bats in rangelands may put their conservation needs at odds with those of obligate grassland species. Focusing rangeland bat conservation on areas that were treed prior to European settlement, such as riparian forests, can provide important areas for bat conservation while minimizing negative impacts on grassland species.}, } @article {pmid30680139, year = {2019}, author = {Badillo-Montaño, R and Aguirre, A and Munguía-Rosas, MA}, title = {Pollinator-mediated interactions between cultivated papaya and co-flowering plant species.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {587-597}, doi = {10.1002/ece3.4781}, pmid = {30680139}, issn = {2045-7758}, abstract = {Many modern crop varieties rely on animal pollination to set fruit and seeds. Intensive crop plantations usually do not provide suitable habitats for pollinators so crop yield may depend on the surrounding vegetation to maintain pollination services. However, little is known about the effect of pollinator-mediated interactions among co-flowering plants on crop yield or the underlying mechanisms. Plant reproductive success is complex, involving several pre- and post-pollination events; however, the current literature has mainly focused on pre-pollination events in natural plant communities. We assessed pollinator sharing and the contribution to pollinator diet in a community of wild and cultivated plants that co-flower with a focal papaya plantation. In addition, we assessed heterospecific pollen transfer to the stigmatic loads of papaya and its effect on fruit and seed production. We found that papaya shared at least one pollinator species with the majority of the co-flowering plants. Despite this, heterospecific pollen transfer in cultivated papaya was low in open-pollinated flowers. Hand-pollination experiments suggest that heterospecific pollen transfer has no negative effect on fruit production or weight, but does reduce seed production. These results suggest that co-flowering plants offer valuable floral resources to pollinators that are shared with cultivated papaya with little or no cost in terms of heterospecific pollen transfer. Although HP reduced seed production, a reduced number of seeds per se are not negative, given that from an agronomic perspective the number of seeds does not affect the monetary value of the papaya fruit.}, } @article {pmid30680138, year = {2019}, author = {Pureswaran, DS and Neau, M and Marchand, M and De Grandpré, L and Kneeshaw, D}, title = {Phenological synchrony between eastern spruce budworm and its host trees increases with warmer temperatures in the boreal forest.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {576-586}, doi = {10.1002/ece3.4779}, pmid = {30680138}, issn = {2045-7758}, abstract = {Climate change is predicted to alter relationships between trophic levels by changing the phenology of interacting species. We tested whether synchrony between two critical phenological events, budburst of host species and larval emergence from diapause of eastern spruce budworm, increased at warmer temperatures in the boreal forest in northeastern Canada. Budburst was up to 4.6 ± 0.7 days earlier in balsam fir and up to 2.8 ± 0.8 days earlier in black spruce per degree increase in temperature, in naturally occurring microclimates. Larval emergence from diapause did not exhibit a similar response. Instead, larvae emerged once average ambient temperatures reached 10°C, regardless of differences in microclimate. Phenological synchrony increased with warmer microclimates, tightening the relationship between spruce budworm and its host species. Synchrony increased by up to 4.5 ± 0.7 days for balsam fir and up to 2.8 ± 0.8 days for black spruce per degree increase in temperature. Under a warmer climate, defoliation could potentially begin earlier in the season, in which case, damage on the primary host, balsam fir may increase. Black spruce, which escapes severe herbivory because of a 2-week delay in budburst, would become more suitable as a resource for the spruce budworm. The northern boreal forest could become more vulnerable to outbreaks in the future.}, } @article {pmid30680137, year = {2019}, author = {Han, Z and Li, W and Zhu, W and Sun, S and Ye, K and Xie, Y and Wang, Z}, title = {Near-complete genome assembly and annotation of the yellow drum (Nibea albiflora) provide insights into population and evolutionary characteristics of this species.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {568-575}, doi = {10.1002/ece3.4778}, pmid = {30680137}, issn = {2045-7758}, abstract = {Yellow drum (Nibea albiflora) is an important fish species in capture fishery and aquaculture in East Asia. We herein report the first and near-complete genome assembly of an ultra-homologous gynogenic female yellow drum using Illumina short sequencing reads. In summary, a total of 154.2 Gb of raw reads were generated via whole-genome sequencing and were assembled to 565.3 Mb genome with a contig N50 size of 50.3 kb and scaffold N50 size of 2.2 Mb (BUSCO completeness of 97.7%), accounting for 97.3%-98.6% of the estimated genome size of this fish. We further identified 22,448 genes using combined methods of ab initio prediction, RNAseq annotation, and protein homology searching, of which 21,614 (96.3%) were functionally annotated in NCBI nr, trEMBL, SwissProt, and KOG databases. We also investigated the nucleotide diversity (around 1/390) of aquacultured individuals and found the genetic diversity of the aquacultured population decreased due to inbreeding. Evolutionary analyses illustrated significantly expanded and extracted gene families, such as myosin and sodium: neurotransmitter symporter (SNF), could help explain swimming motility of yellow drum. The presented genome will be an important resource for future studies on population genetics, conservation, understanding of evolutionary history and genetic breeding of the yellow drum and other Nibea species.}, } @article {pmid30680136, year = {2019}, author = {Bracken, FSA and Rooney, SM and Kelly-Quinn, M and King, JJ and Carlsson, J}, title = {Identifying spawning sites and other critical habitat in lotic systems using eDNA "snapshots": A case study using the sea lamprey Petromyzon marinus L.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {553-567}, doi = {10.1002/ece3.4777}, pmid = {30680136}, issn = {2045-7758}, abstract = {Many aquatic species of conservation concern exist at low densities and are inherently difficult to detect or monitor using conventional methods. However, the introduction of environmental (e)DNA has recently transformed our ability to detect these species and enables effective deployment of limited conservation resources. Identifying areas for breeding, as well as the ecological distribution of species, is vital to the survival or recovery of a conservation species (i.e., areas of critical habitat). In many species, spawning events are associated with a higher relative abundance of DNA released within an aquatic system (i.e., gametes, skin cells etc.), making this the ideal time to monitor these species using eDNA techniques. This study aims to examine whether a "snapshot" eDNA sampling approach (i.e., samples taken at fixed points in chronological time) could reveal areas of critical habitat including spawning sites for our target species Petromyzon marinus. We utilized a species-specific qPCR assay to monitor spatial and temporal patterns in eDNA concentration within two river catchments in Ireland over three consecutive years. We found that eDNA concentration increased at the onset of observed spawning activity and patterns of concentration increased from downstream to upstream over time, suggesting dispersal into the higher reaches as the spawning season progressed. We found P. marinus to be present upstream of several potential barriers to migration, sometimes in significant numbers. Our results also show that the addition of a lamprey-specific fish pass at an "impassable" weir, although assisting in ascent, did not have any significant impact on eDNA concentration upstream after the pass had been installed. eDNA concentration was also found to be significantly correlated with both the number of fish and the number of nests encountered. The application of snapshot sampling techniques for species monitoring therefore has substantial potential for the management of low-density species in fast-moving aquatic systems.}, } @article {pmid30680135, year = {2019}, author = {Rubene, D and Leidefors, M and Ninkovic, V and Eggers, S and Low, M}, title = {Disentangling olfactory and visual information used by field foraging birds.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {545-552}, doi = {10.1002/ece3.4773}, pmid = {30680135}, issn = {2045-7758}, abstract = {Foraging strategies of birds can influence trophic plant-insect networks with impacts on primary plant production. Recent experiments show that some forest insectivorous birds can use herbivore-induced plant volatiles (HIPVs) to locate herbivore-infested trees, but it is unclear how birds combine or prioritize visual and olfactory information when making foraging decisions. Here, we investigated attraction of ground-foraging birds to HIPVs and visible prey in short vegetation on farmland in a series of foraging choice experiments. Birds showed an initial preference for HIPVs when visual information was the same for all choice options (i.e., one experimental setup had all options with visible prey, another setup with hidden prey). However, if the alternatives within an experimental setup included visible prey (without HIPV) in competition with HIPV-only, then birds preferred the visual option over HIPVs. Our results show that olfactory cues can play an important role in birds' foraging choices when visual information contains little variation; however, visual cues are preferred when variation is present. This suggests certain aspects of bird foraging decisions in agricultural habitats are mediated by olfactory interaction mechanisms between birds and plants. We also found that birds from variety of dietary food guilds were attracted to HIPVs; hence, the ability of birds to use plant cues is probably more general than previously thought, and may influence the biological pest control potential of birds on farmland.}, } @article {pmid30680134, year = {2019}, author = {Arso Civil, M and Cheney, B and Quick, NJ and Islas-Villanueva, V and Graves, JA and Janik, VM and Thompson, PM and Hammond, PS}, title = {Variations in age- and sex-specific survival rates help explain population trend in a discrete marine mammal population.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {533-544}, doi = {10.1002/ece3.4772}, pmid = {30680134}, issn = {2045-7758}, abstract = {Understanding the drivers underlying fluctuations in the size of animal populations is central to ecology, conservation biology, and wildlife management. Reliable estimates of survival probabilities are key to population viability assessments, and patterns of variation in survival can help inferring the causal factors behind detected changes in population size. We investigated whether variation in age- and sex-specific survival probabilities could help explain the increasing trend in population size detected in a small, discrete population of bottlenose dolphins Tursiops truncatus off the east coast of Scotland. To estimate annual survival probabilities, we applied capture-recapture models to photoidentification data collected from 1989 to 2015. We used robust design models accounting for temporary emigration to estimate juvenile and adult survival, multistate models to estimate sex-specific survival, and age models to estimate calf survival. We found strong support for an increase in juvenile/adult annual survival from 93.1% to 96.0% over the study period, most likely caused by a change in juvenile survival. Examination of sex-specific variation showed weaker support for this trend being a result of increasing female survival, which was overall higher than for males and animals of unknown sex. Calf survival was lower in the first than second year; a bias in estimating third-year survival will likely exist in similar studies. There was some support first-born calf survival being lower than for calves born subsequently. Coastal marine mammal populations are subject to the impacts of environmental change, increasing anthropogenic disturbance and the effects of management measures. Survival estimates are essential to improve our understanding of population dynamics and help predict how future pressures may impact populations, but obtaining robust information on the life history of long-lived species is challenging. Our study illustrates how knowledge of survival can be increased by applying a robust analytical framework to photoidentification data.}, } @article {pmid30680133, year = {2019}, author = {Denis, V and Chen, JW and Chen, Q and Hsieh, YE and Lin, YV and Wang, CW and Wang, HY and Sturaro, N}, title = {Biogeography of functional trait diversity in the Taiwanese reef fish fauna.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {522-532}, doi = {10.1002/ece3.4771}, pmid = {30680133}, issn = {2045-7758}, abstract = {The richness of Taiwanese reef fish species is inversely correlated to latitude as a direct consequence of the abiotic environment and its effects on benthic habitats. However, to date, no studies have investigated the variations in the diversity of traits (FD) linked with the role of these fishes in the ecosystem. FD is usually considered more sensitive than species richness in detecting early changes in response to disturbances, and therefore could serve as an indicator of ecological resilience to environmental changes. Here, we aim to characterize FD in the Taiwanese reef fish fauna and to document its regional variations. Six traits were used to categorize the 1,484 reef fish species occurring in four environmentally contrasted regions around Taiwan. The number of unique trait combinations (FEs), their richness (FRic), their redundancy (FR), their over-redundancy (FOR), and their vulnerability (FV) were compared among these regions. Overall, 416 FEs were identified. Their number decreased from south to north in step with regional species richness but FRic remained similar among regions. FR and FOR were higher to the south. At the local scale, variations in FEs and FRic are in concordance with the worldwide pattern of FD. High-latitude, impoverished fish assemblages, offer a range of trait combinations similar to diversified tropical assemblages. Increasing diversity in the latter mainly contributes to raising FR and supports already over-redundant entities. High vulnerability makes many combinations highly sensitive to species loss, and was higher at intermediate latitudes when using a fine resolution in trait categories. It suggests that the loss of FEs may first be characterized by an increase in their vulnerability, a pattern that could have been overlooked in previous global scale analyses. Overall, this study provides new insights into reef fish trait biogeography with potential ramifications for ecosystem functioning.}, } @article {pmid30680132, year = {2019}, author = {Apfelbeck, B and Haussmann, MF and Boner, W and Flinks, H and Griffiths, K and Illera, JC and Mortega, KG and Sisson, Z and Smiddy, P and Helm, B}, title = {Divergent patterns of telomere shortening in tropical compared to temperate stonechats.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {511-521}, doi = {10.1002/ece3.4769}, pmid = {30680132}, issn = {2045-7758}, abstract = {Telomeres have emerged as important biomarkers of health and senescence as they predict chances of survival in various species. Tropical birds live in more benign environments with lower extrinsic mortality and higher juvenile and adult survival than temperate birds. Therefore, telomere biology may play a more important role in tropical compared to temperate birds. We measured mean telomere length of male stonechats (Saxicola spp.) at four age classes from tropical African and temperate European breeding regions. Tropical and temperate stonechats had similarly long telomeres as nestlings. However, while in tropical stonechats pre-breeding first-years had longer telomeres than nestlings, in temperate stonechats pre-breeding first-years had shorter telomeres than nestlings. During their first breeding season, telomere length was again similar between tropical and temperate stonechats. These patterns may indicate differential survival of high-quality juveniles in tropical environments. Alternatively, more favorable environmental conditions, that is, extended parental care, may enable tropical juveniles to minimize telomere shortening. As suggested by previous studies, our results imply that variation in life history and life span may be reflected in different patterns of telomere shortening rather than telomere length. Our data provide first evidence that distinct selective pressures in tropical and temperate environments may be reflected in diverging patterns of telomere loss in birds.}, } @article {pmid30680131, year = {2019}, author = {Kerr, Q and Fuentes-Pardo, AP and Kho, J and McDermid, JL and Ruzzante, DE}, title = {Temporal stability and assignment power of adaptively divergent genomic regions between herring (Clupea harengus) seasonal spawning aggregations.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {500-510}, doi = {10.1002/ece3.4768}, pmid = {30680131}, issn = {2045-7758}, abstract = {Atlantic herring (Clupea harengus), a vital ecosystem component and target of the largest Northwest Atlantic pelagic fishery, undergo seasonal spawning migrations that result in elusive sympatric population structure. Herring spawn mostly in fall or spring, and genomic differentiation was recently detected between these groups. Here we used a subset of this differentiation, 66 single nucleotide polymorphisms (SNPs) to analyze the temporal dynamics of this local adaptation and the applicability of SNP subsets in stock assessment. We showed remarkable temporal stability of genomic differentiation corresponding to spawning season, between samples taken a decade apart (2005 N = 90 vs. 2014 N = 71) in the Gulf of St. Lawrence, and new evidence of limited interbreeding between spawning components. We also examined an understudied and overexploited herring population in Bras d'Or lake (N = 97); using highly reduced SNP panels (NSNPs > 6), we verified little-known sympatric spawning populations within this unique inland sea. These results describe consistent local adaptation, arising from asynchronous reproduction in a migratory and dynamic marine species. Our research demonstrates the efficiency and precision of SNP-based assessments of sympatric subpopulations; and indeed, this temporally stable local adaptation underlines the importance of such fine-scale management practices.}, } @article {pmid30680130, year = {2019}, author = {Tso, KL and Allan, GJ}, title = {Environmental variation shapes genetic variation in Bouteloua gracilis: Implications for restoration management of natural populations and cultivated varieties in the southwestern United States.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {482-499}, doi = {10.1002/ece3.4767}, pmid = {30680130}, issn = {2045-7758}, abstract = {With the increasing frequency of large-scale restoration efforts, the need to understand the adaptive genetic structure of natural plant populations and their relation to heavily utilized cultivars is critical. Bouteloua gracilis (blue grama) is a wind-dispersed, perennial grass consisting of several cytotypes (2n = 2×-6×) with a widespread distribution in western North America. The species is locally dominant and used regularly in restoration treatments. Using amplified fragment length polymorphism (AFLP) and cpDNA analyses, we assessed the genetic variability and adaptive genetic structure of blue grama within and among 44 sampling sites that are representative of the species' environmental and habitat diversity in the southwestern United States. Five cultivars were also included to investigate genetic diversity and differentiation in natural versus cultivated populations. Three main findings resulted from this study: (a) Ninety-four polymorphic AFLP markers distinguished two population clusters defined largely by samples on and off the Colorado Plateau; (b) substructure of samples on the Colorado Plateau was indicated by genetic divergence between boundary and interior regions, and was supported by cytotype distribution and cpDNA analysis; and (c) six AFLP markers were identified as "outliers," consistent with being under selection. These loci were significantly correlated to mean annual temperature, mean annual precipitation, precipitation of driest quarter, and precipitation of wettest quarter in natural populations, but not in cultivated samples. Marker × environment relationships were found to be largely influenced by cytotype and cultivar development. Our results demonstrate that blue grama is genetically variable, and exhibits genetic structure, which is shaped, in part, by environmental variability across the Colorado Plateau. Information from our study can be used to guide the selection of seed source populations for commercial development and long-term conservation management of B. gracilis, which could include genetic assessments of diversity and the adaptive potential of both natural and cultivated populations for wildland restoration.}, } @article {pmid30680129, year = {2019}, author = {Rubin, MJ and Schmid, KM and Friedman, J}, title = {Assortative mating by flowering time and its effect on correlated traits in variable environments.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {471-481}, doi = {10.1002/ece3.4765}, pmid = {30680129}, issn = {2045-7758}, abstract = {Reproductive timing is a key life-history trait that impacts the pool of available mates, the environment experienced during flowering, and the expression of other traits through genetic covariation. Selection on phenology, and its consequences on other life-history traits, has considerable implications in the context of ongoing climate change and shifting growing seasons. To test this, we grew field-collected seed from the wildflower Mimulus guttatus in a greenhouse to assess the standing genetic variation for flowering time and covariation with other traits. We then created full-sib families through phenological assortative mating and grew offspring in three photoperiod treatments representing seasonal variation in daylength. We find substantial quantitative genetic variation for the onset of flowering time, which covaried with vegetative traits. The assortatively-mated offspring varied in their critical photoperiod by over two hours, so that families differed in their probability of flowering across treatments Allocation to flowering and vegetative growth changed across the daylength treatments, with consistent direction and magnitude of covariation among flowering time and other traits. Our results suggest that future studies of flowering time evolution should consider the joint evolution of correlated traits and shifting seasonal selection to understand how environmental variation influences life histories.}, } @article {pmid30680128, year = {2019}, author = {Hauser, SS and Walker, L and Leberg, PL}, title = {Asymmetrical gene flow of the recently delisted passerine black-capped vireo (Vireo atricapilla) indicates source-sink dynamics in central Texas.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {463-470}, doi = {10.1002/ece3.4764}, pmid = {30680128}, issn = {2045-7758}, abstract = {Habitat fragmentation can produce metapopulations or source-sink systems in which dispersal in crucial for population maintenance. Our objective was to investigate connectivity among black-capped vireo (Vireo atricapilla) populations in tandem with a demographic study (Biological Conservation, 2016, 203, 108-118) to elucidate if central Texas populations act as a source-sink system. We genotyped 343 individuals at 12 microsatellite loci to elucidate the movement ecology of the black-capped vireo in central Texas surrounding Fort Hood; the largest and most stable breeding population of black-capped vireos inhabit Fort Hood. To gain insight into gene flow among populations, we analyzed genetic differentiation, migration rates, number of migrants, and parentage. We found statistically significant, but low levels of genetic differentiation among several populations, suggesting some limited restriction to gene flow. Across approaches to estimate migration, we found consistent evidence for asymmetrical movement from Fort Hood to the other central Texas sites consistent with source-sink dynamics. Our results are complementary to black-capped vireo demographic studies done in tandem showing that portions of Fort Hood are acting as a source population to smaller central Texas populations.}, } @article {pmid30680127, year = {2019}, author = {Dorková, M and Naďo, L and Jarčuška, B and Kaňuch, P}, title = {Size-dependent mating pattern in a nuptial gift-giving insect.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {454-462}, doi = {10.1002/ece3.4763}, pmid = {30680127}, issn = {2045-7758}, abstract = {The reproductive interests of females and males often diverge in terms of the number of mating partners, an individual's phenotype, origin, genes, and parental investment. This conflict may lead to a variety of sex-specific adaptations and also affect mate choice in both sexes. We conducted an experiment with the bush-cricket Pholidoptera griseoaptera (Orthoptera, Tettigoniidae), a species in which females receive direct nutritional benefits during mating. Mated individuals could be assigned due to the genotype of male spermatodoses, which are stored in the female's spermatheca. After 3 weeks of possible copulations in established mating groups which were random replications with four females and males we did not find consistent assortative mating preference regarding to body size of mates. However, our results showed that the frequency of within-pair copulations (192 analyzed mating events in 128 possible pairwise combinations) was positively associated with the body size of both mated individuals with significant interaction between sexes (having one mate very large, association between body size and the number of copulations has weaken). Larger individuals also showed a higher degree of polygamy. This suggests that body size of this nuptial gift-giving insect species is an important sexual trait according to which both sexes choose their optimal mating partner.}, } @article {pmid30680126, year = {2019}, author = {Flores-Manzanero, A and Luna-Bárcenas, MA and Dyer, RJ and Vázquez-Domínguez, E}, title = {Functional connectivity and home range inferred at a microgeographic landscape genetics scale in a desert-dwelling rodent.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {437-453}, doi = {10.1002/ece3.4762}, pmid = {30680126}, issn = {2045-7758}, abstract = {Gene flow in animals is limited or facilitated by different features within the landscape matrix they inhabit. The landscape representation in landscape genetics (LG) is traditionally modeled as resistance surfaces (RS), where novel optimization approaches are needed for assigning resistance values that adequately avoid subjectivity. Also, desert ecosystems and mammals are scarcely represented in LG studies. We addressed these issues by evaluating, at a microgeographic scale, the effect of landscape features on functional connectivity of the desert-dwelling Dipodomys merriami. We characterized genetic diversity and structure with microsatellites loci, estimated home ranges and movement of individuals using telemetry-one of the first with rodents, generated a set of individual and composite environmental surfaces based on hypotheses of variables influencing movement, and assessed how these variables relate to individual-based gene flow. Genetic diversity and structure results evidenced a family-induced pattern driven by first-order-related individuals, notably determining landscape genetic inferences. The vegetation cover and soil resistance optimized surface (NDVI) were the best-supported model and a significant predictor of individual genetic distance, followed by humidity and NDVI+humidity. Based on an accurate definition of thematic resolution, we also showed that vegetation is better represented as continuously (vs. categorically) distributed. Hence, with a nonsubjective optimization framework for RS and telemetry, we were able to describe that vegetation cover, soil texture, and climatic variables influence D. merriami's functional connectivity at a microgeographic scale, patterns we could further explain based on the home range, habitat use, and activity observed between sexes. We describe the relationship between environmental features and some aspects of D. merriami's behavior and physiology.}, } @article {pmid30680125, year = {2019}, author = {Li, R}, title = {Protecting rare and endangered species under climate change on the Qinghai Plateau, China.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {427-436}, doi = {10.1002/ece3.4761}, pmid = {30680125}, issn = {2045-7758}, abstract = {Climate change-induced species range shift may pose severe challenges to species conservation. The Qinghai-Tibet Plateau is the highest and biggest plateau, and also one of the most sensitive areas to global warming in the world, which provides important shelters for a unique assemblage of species. Here, ecological niche-based model was employed to project the potential distributions of 59 key rare and endangered species under three climate change scenarios (RCP2.6, RCP4.5 and RCP8.5) in Qinghai Province. I assessed the potential impacts of climate change on these key species (habitats, species richness and turnover) and effectiveness of nature reserves (NRs) in protecting these species. The results revealed that that climate change would shrink the geographic ranges of about a third studied species and expand the habitats for two thirds of these species, which would thus alter the conservation value of some local areas and conservation effectiveness of some NRs in Qinghai Province. Some regions require special attention as they are expected to experience significant changes in species turnover, species richness or newly colonized species in the future, including Haidong, Haibei and Haixi junctions, the southwestern Yushu, Qinghai Nuomuhong Provincial NR, Qinghai Qaidam and Haloxylon Forest NR. The Haidong and the eastern part of Haibei, are projected to have high species richness and conservation value in both current and future, but they are currently not protected, and thus require extra protection in the future. The results could provide the first basis on the high latitude region to formulate biodiversity conservation strategies on climate change adaptation.}, } @article {pmid30680124, year = {2019}, author = {Thorbjørnsen, SH and Moland, E and Simpfendorfer, C and Heupel, M and Knutsen, H and Olsen, EM}, title = {Potential of a no-take marine reserve to protect home ranges of anadromous brown trout (Salmo trutta).}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {417-426}, doi = {10.1002/ece3.4760}, pmid = {30680124}, issn = {2045-7758}, abstract = {The extent to which no-take marine reserves can benefit anadromous species requires examination. Here, we used acoustic telemetry to investigate the spatial behavior of anadromous brown trout (sea trout, Salmo trutta) in relation to a small marine reserve (~1.5 km2) located inside a fjord on the Norwegian Skagerrak coast. On average, sea trout spent 42.3 % (±5.0% SE) of their time in the fjord within the reserve, a proportion similar to the area of the reserve relative to that of the fjord. On average, sea trout tagged inside the reserve received the most protection, although the level of protection decreased marginally with increasing home range size. Furthermore, individuals tagged outside the reserve received more protection with increasing home range size, potentially opposing selection toward smaller home range sizes inflicted on fish residing within reserves, or through selective fishing methods like angling. Monthly sea trout home ranges in the marine environment were on average smaller than the reserve, with a mean of 0.430 (±0.0265 SE) km2. Hence, the reserve is large enough to protect the full home range of some individuals residing in the reserve. Synthesis and applications: In general, the reserve protects sea trout to a varying degree depending on their individual behavior. These findings highlight evolutionary implications of spatial protection and can guide managers in the design of marine reserves and networks that preserve variation in target species' home range size and movement behavior.}, } @article {pmid30680123, year = {2019}, author = {Marie-Orleach, L and Bailey, NW and Ritchie, MG}, title = {Social effects on fruit fly courtship song.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {410-416}, doi = {10.1002/ece3.4759}, pmid = {30680123}, issn = {2045-7758}, abstract = {Courtship behavior in Drosophila has often been described as a classic innate behavioral repertoire, but more recently extensive plasticity has been described. In particular, prior exposure to acoustic signals of con- or heterspecific males can change courtship traits in both sexes that are liable to be important in reproductive isolation. However, it is unknown whether male courtship song itself is socially plastic. We examined courtship song plasticity of two species in the Drosophila melanogaster subgroup. Sexual isolation between the species is influenced by two male song traits, the interpulse interval (IPI) and sinesong frequency (SSF). Neither of these showed plasticity when males had prior experience of con- and heterospecific social partners. However, males of both species produced longer bursts of song during courtship when they were exposed to social partners (either con- or heterospecific) than when they were reared in isolation. D. melanogaster carrying mutations affecting short- or medium-term memory showed a similar response to the social environment, not supporting a role for learning. Our results demonstrate that the amount of song a male produces during courtship is plastic depending on the social environment, which might reflect the advantage of being able to respond to variation in intrasexual competition, but that song structure itself is relatively inflexible, perhaps due to strong selection against hybridization.}, } @article {pmid30680122, year = {2019}, author = {Doellman, MM and Egan, SP and Ragland, GJ and Meyers, PJ and Hood, GR and Powell, THQ and Lazorchak, P and Hahn, DA and Berlocher, SH and Nosil, P and Feder, JL}, title = {Standing geographic variation in eclosion time and the genomics of host race formation in Rhagoletis pomonella fruit flies.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {393-409}, doi = {10.1002/ece3.4758}, pmid = {30680122}, issn = {2045-7758}, abstract = {Taxa harboring high levels of standing variation may be more likely to adapt to rapid environmental shifts and experience ecological speciation. Here, we characterize geographic and host-related differentiation for 10,241 single nucleotide polymorphisms in Rhagoletis pomonella fruit flies to infer whether standing genetic variation in adult eclosion time in the ancestral hawthorn (Crataegus spp.)-infesting host race, as opposed to new mutations, contributed substantially to its recent shift to earlier fruiting apple (Malus domestica). Allele frequency differences associated with early vs. late eclosion time within each host race were significantly related to geographic genetic variation and host race differentiation across four sites, arrayed from north to south along a 430-km transect, where the host races co-occur in sympatry in the Midwest United States. Host fruiting phenology is clinal, with both apple and hawthorn trees fruiting earlier in the North and later in the South. Thus, we expected alleles associated with earlier eclosion to be at higher frequencies in northern populations. This pattern was observed in the hawthorn race across all four populations; however, allele frequency patterns in the apple race were more complex. Despite the generally earlier eclosion timing of apple flies and corresponding apple fruiting phenology, alleles on chromosomes 2 and 3 associated with earlier emergence were paradoxically at lower frequency in the apple than hawthorn host race across all four sympatric sites. However, loci on chromosome 1 did show higher frequencies of early eclosion-associated alleles in the apple than hawthorn host race at the two southern sites, potentially accounting for their earlier eclosion phenotype. Thus, although extensive clinal genetic variation in the ancestral hawthorn race exists and contributed to the host shift to apple, further study is needed to resolve details of how this standing variation was selected to generate earlier eclosing apple fly populations in the North.}, } @article {pmid30680121, year = {2019}, author = {Helmkampf, M and Bellinger, MR and Frazier, M and Takabayashi, M}, title = {Symbiont type and environmental factors affect transcriptome-wide gene expression in the coral Montipora capitata.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {378-392}, doi = {10.1002/ece3.4756}, pmid = {30680121}, issn = {2045-7758}, abstract = {Reef-building corals may harbor genetically distinct lineages of endosymbiotic dinoflagellates in the genus Symbiodinium, which have been shown to affect important colony properties, including growth rates and resilience against environmental stress. However, the molecular processes underlying these differences are not well understood. In this study, we used whole transcriptome sequencing (RNA-seq) to assess gene expression differences between 27 samples of the coral Montipora capitata predominantly hosting two different Symbiodinium types in clades C and D. The samples were further characterized by their origin from two field sites on Hawai'i Island with contrasting environmental conditions. We found that transcriptome-wide gene expression profiles clearly separated by field site first, and symbiont clade second. With 273 differentially expressed genes (DEGs, 1.3% of all host transcripts), symbiont clade had a measurable effect on host gene expression, but the effect of field site proved almost an order of magnitude higher (1,957 DEGs, 9.6%). According to SNP analysis, we found moderate evidence for host genetic differentiation between field sites (FST = 0.046) and among corals harboring alternative symbiont clades (FST = 0.036), suggesting that site-related gene expression differences are likely due to a combination of local adaptation and acclimatization to environmental factors. The correlation between host gene expression and symbiont clade may be due to several factors, including host genotype or microhabitat selecting for alternative clades, host physiology responding to different symbionts, or direct modulation of host gene expression by Symbiodinium. However, the magnitude of these effects at the level of transcription was unexpectedly small considering the contribution of symbiont type to holobiont phenotype.}, } @article {pmid30680120, year = {2019}, author = {Mustafina, FU and Yi, DK and Choi, K and Shin, CH and Tojibaev, KS and Downie, SR}, title = {A comparative analysis of complete plastid genomes from Prangos fedtschenkoi and Prangos lipskyi (Apiaceae).}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {364-377}, doi = {10.1002/ece3.4753}, pmid = {30680120}, issn = {2045-7758}, abstract = {Prangos fedtschenkoi (Regel & Schmalh.) Korovin and P. lipskyi Korovin (Apiaceae) are rare plant species endemic to mountainous regions of Middle Asia. Both are edificators of biotic communities and valuable resource plants. The results of recent phylogenetic analyses place them in Prangos subgen. Koelzella (M. Hiroe) Lyskov & Pimenov and suggest they may possibly represent sister species. To aid in development of molecular markers useful for intraspecific phylogeographic and population-level genetic studies of these ecologically and economically important plants, we determined their complete plastid genome sequences and compared the results obtained to several previously published plastomes of Apiaceae. The plastomes of P. fedtschenkoi and P. lipskyi are typical of Apiaceae and most other higher plant plastid DNAs in their sizes (153,626 and 154,143 bp, respectively), structural organization, gene arrangement, and gene content (with 113 unique genes). A total of 49 and 48 short sequence repeat (SSR) loci of 10 bp or longer were detected in P. fedtschenkoi and P. lipskyi plastomes, respectively, representing 42-43 mononucleotides and 6 AT dinucleotides. Seven tandem repeats of 30 bp or longer with a sequence identity ≥90% were identified in each plastome. Further comparisons revealed 319 polymorphic sites between the plastomes (IR, 21; LSC, 234; SSC, 64), representing 43.8% transitions (Ts), 56.1% transversions (Tv), and a Ts/Tv ratio of 0.78. Within genic regions, two indel events were observed in rpoA (6 and 51 bp) and ycf1 (3 and 12 bp), and one in ndhF (6 bp). The most variable intergenic spacer region was that of accD/psaI, with 21.1% nucleotide divergence. Each Prangos species possessed one of two separate inversions (either 5 bp in ndhB intron or 9 bp in petB intron), and these were predicted to form hairpin structures with flanking repeat sequences of 18 and 19 bp, respectively. Both species have also incorporated novel DNA in the LSC region adjacent to the LSC/IRa junction, and BLAST searches revealed it had a 100 bp match (86% sequence identity) to noncoding mitochondrial DNA. Prangos-specific primers were developed for the variable accD/psaI intergenic spacer and preliminary PCR-surveys suggest that this region will be useful for future phylogeographic and population-level studies.}, } @article {pmid30680119, year = {2019}, author = {Milleret, C and Dupont, P and Bonenfant, C and Brøseth, H and Flagstad, Ø and Sutherland, C and Bischof, R}, title = {A local evaluation of the individual state-space to scale up Bayesian spatial capture-recapture.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {352-363}, doi = {10.1002/ece3.4751}, pmid = {30680119}, issn = {2045-7758}, abstract = {Spatial capture-recapture models (SCR) are used to estimate animal density and to investigate a range of problems in spatial ecology that cannot be addressed with traditional nonspatial methods. Bayesian approaches in particular offer tremendous flexibility for SCR modeling. Increasingly, SCR data are being collected over very large spatial extents making analysis computational intensive, sometimes prohibitively so. To mitigate the computational burden of large-scale SCR models, we developed an improved formulation of the Bayesian SCR model that uses local evaluation of the individual state-space (LESS). Based on prior knowledge about a species' home range size, we created square evaluation windows that restrict the spatial domain in which an individual's detection probability (detector window) and activity center location (AC window) are estimated. We used simulations and empirical data analyses to assess the performance and bias of SCR with LESS. LESS produced unbiased estimates of SCR parameters when the AC window width was ≥5σ (σ: the scale parameter of the half-normal detection function), and when the detector window extended beyond the edge of the AC window by 2σ. Importantly, LESS considerably decreased the computation time needed for fitting SCR models. In our simulations, LESS increased the computation speed of SCR models up to 57-fold. We demonstrate the power of this new approach by mapping the density of an elusive large carnivore-the wolverine (Gulo gulo)-with an unprecedented resolution and across the species' entire range in Norway (> 200,000 km2). Our approach helps overcome a major computational obstacle to population and landscape-level SCR analyses. The LESS implementation in a Bayesian framework makes the customization and fitting of SCR accessible for practitioners working at scales that are relevant for conservation and management.}, } @article {pmid30680118, year = {2019}, author = {De Gasperin, O and Duarte, A and English, S and Attisano, A and Kilner, RM}, title = {The early-life environment and individual plasticity in life-history traits.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {339-351}, doi = {10.1002/ece3.4749}, pmid = {30680118}, issn = {2045-7758}, abstract = {We tested whether the early-life environment can influence the extent of individual plasticity in a life-history trait. We asked: can the early-life environment explain why, in response to the same adult environmental cue, some individuals invest more than others in current reproduction? Moreover, can it additionally explain why investment in current reproduction trades off against survival in some individuals, but is positively correlated with survival in others? We addressed these questions using the burying beetle, which breeds on small carcasses and sometimes carries phoretic mites. These mites breed alongside the beetle, on the same resource, and are a key component of the beetle's early-life environment. We exposed female beetles to mites twice during their lives: during their development as larvae and again as adults during their first reproductive event. We measured investment in current reproduction by quantifying average larval mass and recorded the female's life span after breeding to quantify survival. We found no effect of either developing or breeding alongside mites on female reproductive investment, nor on her life span, nor did developing alongside mites influence her size. In post hoc analyses, where we considered the effect of mite number (rather than their mere presence/absence) during the female's adult breeding event, we found that females invested more in current reproduction when exposed to greater mite densities during reproduction, but only if they had been exposed to mites during development as well. Otherwise, they invested less in larvae at greater mite densities. Furthermore, females that had developed with mites exhibited a trade-off between investment in current reproduction and future survival, whereas these traits were positively correlated in females that had developed without mites. The early-life environment thus generates individual variation in life-history plasticity. We discuss whether this is because mites influence the resources available to developing young or serve as important environmental cues.}, } @article {pmid30680117, year = {2019}, author = {Duffy, E and Archer, CR and Sharma, MD and Prus, M and Joag, RA and Radwan, J and Wedell, N and Hosken, DJ}, title = {Wolbachia infection can bias estimates of intralocus sexual conflict.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {328-338}, doi = {10.1002/ece3.4744}, pmid = {30680117}, issn = {2045-7758}, abstract = {Males and females share most of their genome and develop many of the same traits. However, each sex frequently has different optimal values for these shared traits, creating intralocus sexual conflict. This conflict has been observed in wild and laboratory populations of insects and affects important evolutionary processes such as sexual selection, the maintenance of genetic variation, and possibly even speciation. Given the broad impacts of intralocus conflict, accurately detecting and measuring it is important. A common way to detect intralocus sexual conflict is to calculate the intersexual genetic correlation for fitness, with negative values suggesting conflict. Here, we highlight a potential confounder of this measure-cytoplasmic incompatibility caused by the intracellular parasite Wolbachia. Infection with Wolbachia can generate negative intersexual genetic correlations for fitness in insects, suggestive of intralocus sexual conflict. This is because cytoplasmic incompatibility reduces the fitness of uninfected females mated to infected males, while uninfected males will not suffer reductions in fitness if they mate with infected females and may even be fitter than infected males. This can lead to strong negative intersexual genetic correlations for fitness, mimicking intralocus conflict. We illustrate this issue using simulations and then present Drosophila simulans data that show how reproductive incompatibilities caused by Wolbachia infection can generate signals of intralocus sexual conflict. Given that Wolbachia infection in insect populations is pervasive, but populations usually contain both infected and uninfected individuals providing scope for cytoplasmic incompatibility, this is an important consideration for sexual conflict research but one which, to date, has been largely underappreciated.}, } @article {pmid30680116, year = {2019}, author = {Osada, Y and Kuriyama, T and Asada, M and Yokomizo, H and Miyashita, T}, title = {Estimating range expansion of wildlife in heterogeneous landscapes: A spatially explicit state-space matrix model coupled with an improved numerical integration technique.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {318-327}, doi = {10.1002/ece3.4739}, pmid = {30680116}, issn = {2045-7758}, abstract = {Dispersal as well as population growth is a key demographic process that determines population dynamics. However, determining the effects of environmental covariates on dispersal from spatial-temporal abundance proxy data is challenging owing to the complexity of model specification for directional dispersal permeability and the extremely high computational loads for numerical integration. In this paper, we present a case study estimating how environmental covariates affect the dispersal of Japanese sika deer by developing a spatially explicit state-space matrix model coupled with an improved numerical integration technique (Markov chain Monte Carlo with particle filters). In particular, we explored the environmental drivers of inhomogeneous range expansion, characteristic of animals with short dispersal. Our model framework successfully reproduced the complex population dynamics of sika deer, including rapid changes in densely populated areas and distribution fronts within a decade. Furthermore, our results revealed that the inhomogeneous range expansion of sika deer seemed to be primarily caused by the dispersal process (i.e., movement barriers in fragmented forests) rather than population growth. Our state-space matrix model enables the inference of population dynamics for a broad range of organisms, even those with low dispersal ability, in heterogeneous landscapes, and could address many pressing issues in conservation biology and ecosystem management.}, } @article {pmid30680115, year = {2019}, author = {Abercrombie, ST and Koprowski, JL and Nichols, MH and Fehmi, JS}, title = {Native lagomorphs suppress grass establishment in a shrub-encroached, semiarid grassland.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {307-317}, doi = {10.1002/ece3.4730}, pmid = {30680115}, issn = {2045-7758}, abstract = {Shrub encroachment into arid grasslands has been associated with reduced grass abundance, increased soil erosion, and local declines in biodiversity. Livestock overgrazing and the associated reduction of fine fuels has been a primary driver of shrub encroachment in the southwestern United States, but shrublands continue to persist despite livestock removal and grassland restoration efforts. We hypothesized that an herbivory feedback from native mammals may contribute to continued suppression of grasses after the removal of livestock. Our herbivore exclusion experiment in southeastern Arizona included five treatment levels and allowed access to native mammals based on their relative body size, separating the effects of rodents, lagomorphs, and mule deer. We included two control treatments and replicated each treatment 10 times (n = 50). We introduced uniform divisions of lawn sod (Cynodon dactylon) into each exclosure for 24-hr periods prior to (n = 2) and following (n = 2) the monsoon rains and used motion-activated cameras to document herbivore visitations. In the pre-monsoon trials, treatments that allowed lagomorph access had less sod biomass relative to other treatments (p < 0.001), averaging 44% (SD 36%) and 29% (SD 45%) remaining biomass after the 24-hr trial periods. Following the onset of monsoons, differences in remaining biomass among treatments disappeared. Desert cottontails (Sylvilagus audubonii) were detected more frequently than any of the other 11 herbivore species present at the site, accounting for 83% of detections during the pre-monsoon trials. Significantly more (p < 0.001) desert cottontails were detected during the pre-monsoon trials (2,077) compared to the post-monsoon trials (174), which coincided with biomass removal from lagomorph accessible treatments. We conclude that desert cottontails are significant consumers of herbaceous vegetation in shrub-encroached arid grasslands and they, along with other native herbivores, may act as a biotic feedback contributing to the competitive advantage and persistence of shrubs.}, } @article {pmid30680114, year = {2019}, author = {Yewers, MSC and Stuart-Fox, D and McLean, CA}, title = {Space use and genetic structure do not maintain color polymorphism in a species with alternative behavioral strategies.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {295-306}, doi = {10.1002/ece3.4729}, pmid = {30680114}, issn = {2045-7758}, abstract = {Space use including territoriality and spatial arrangement within a population can reveal important information on the nature, dynamics, and evolutionary maintenance of alternative strategies in color polymorphic species. Despite the prevalence of color polymorphic species as model systems in evolutionary biology, the interaction between space use and genetic structuring of morphs within populations has rarely been examined. Here, we assess the spatial and genetic structure of male throat color morphs within a population of the tawny dragon lizard, Ctenophorus decresii. Male color morphs do not differ in morphology but differ in aggressive and antipredator behaviors as well as androgen levels. Despite these behavioral and endocrine differences, we find that color morphs do not differ in territory size, with their spatial arrangement being essentially random with respect to each other. There were no differences in genetic diversity or relatedness between morphs; however, there was significant, albeit weak, genetic differentiation between morphs, which was unrelated to geographic distance between individuals. Our results indicate potential weak barriers to gene flow between some morphs, potentially due to nonrandom pre- or postcopulatory mate choice or postzygotic genetic incompatibilities. However, space use, spatial structure, and nonrandom mating do not appear to be primary mechanisms maintaining color polymorphism in this system, highlighting the complexity and variation in alternative strategies associated with color polymorphism.}, } @article {pmid30680113, year = {2019}, author = {Haueisen, J and Möller, M and Eschenbrenner, CJ and Grandaubert, J and Seybold, H and Adamiak, H and Stukenbrock, EH}, title = {Highly flexible infection programs in a specialized wheat pathogen.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {275-294}, doi = {10.1002/ece3.4724}, pmid = {30680113}, issn = {2045-7758}, abstract = {Many filamentous plant pathogens exhibit high levels of genomic variability, yet the impact of this variation on host-pathogen interactions is largely unknown. We have addressed host specialization in the wheat pathogen Zymoseptoria tritici. Our study builds on comparative analyses of infection and gene expression phenotypes of three isolates and reveals the extent to which genomic variation translates into phenotypic variation. The isolates exhibit genetic and genomic variation but are similarly virulent. By combining confocal microscopy, disease monitoring, staining of ROS, and comparative transcriptome analyses, we conducted a detailed comparison of the infection processes of these isolates in a susceptible wheat cultivar. We characterized four core infection stages: establishment, biotrophic growth, lifestyle transition, and necrotrophic growth and asexual reproduction that are shared by the three isolates. However, we demonstrate differentiated temporal and spatial infection development and significant differences in the expression profiles of the three isolates during the infection stages. More than 20% of the genes were differentially expressed and these genes were located significantly closer to transposable elements, suggesting an impact of epigenetic regulation. Further, differentially expressed genes were enriched in effector candidates suggesting that isolate-specific strategies for manipulating host defenses are present in Z. tritici. We demonstrate that individuals of a host-specialized pathogen have highly differentiated infection programs characterized by flexible infection development and functional redundancy. This illustrates how high genetic diversity in pathogen populations results in highly differentiated infection phenotypes, which fact needs to be acknowledged to understand host-pathogen interactions and pathogen evolution.}, } @article {pmid30680112, year = {2019}, author = {Munden, R and Börger, L and Wilson, RP and Redcliffe, J and Loison, A and Garel, M and Potts, JR}, title = {Making sense of ultrahigh-resolution movement data: A new algorithm for inferring sites of interest.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {265-274}, doi = {10.1002/ece3.4721}, pmid = {30680112}, issn = {2045-7758}, abstract = {Decomposing the life track of an animal into behavioral segments is a fundamental challenge for movement ecology. The proliferation of high-resolution data, often collected many times per second, offers much opportunity for understanding animal movement. However, the sheer size of modern data sets means there is an increasing need for rapid, novel computational techniques to make sense of these data. Most existing methods were designed with smaller data sets in mind and can thus be prohibitively slow. Here, we introduce a method for segmenting high-resolution movement trajectories into sites of interest and transitions between these sites. This builds on a previous algorithm of Benhamou and Riotte-Lambert (2012). Adapting it for use with high-resolution data. The data's resolution removed the need to interpolate between successive locations, allowing us to increase the algorithm's speed by approximately two orders of magnitude with essentially no drop in accuracy. Furthermore, we incorporate a color scheme for testing the level of confidence in the algorithm's inference (high = green, medium = amber, low = red). We demonstrate the speed and accuracy of our algorithm with application to both simulated and real data (Alpine cattle at 1 Hz resolution). On simulated data, our algorithm correctly identified the sites of interest for 99% of "high confidence" paths. For the cattle data, the algorithm identified the two known sites of interest: a watering hole and a milking station. It also identified several other sites which can be related to hypothesized environmental drivers (e.g., food). Our algorithm gives an efficient method for turning a long, high-resolution movement path into a schematic representation of broadscale decisions, allowing a direct link to existing point-to-point analysis techniques such as optimal foraging theory. It is encoded into an R package called SitesInterest, so should serve as a valuable tool for making sense of these increasingly large data streams.}, } @article {pmid30680111, year = {2019}, author = {Graham, J and Kimble, M}, title = {Visualizing uncertainty in habitat suitability models with the hyper-envelope modeling interface, version 2.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {251-264}, doi = {10.1002/ece3.4720}, pmid = {30680111}, issn = {2045-7758}, abstract = {Habitat suitability models (HSMs) are popular and used for a wide variety of applications but most do not include analysis of the uncertainty of the model outputs. Additionally, some overfit the data and few allow the ability to fill data gaps with expert opinion. HEMI 1 addressed issues with overfitting data and allowed models to incorporate both occurrence data and expert opinion. HEMI 2 improves on HEMI 1 with a simplified interface and the ability to inject random noise into occurrence locations and environmental variable values to generate uncertainty maps. HEMI 2 uses Monte Carlo methods to perform uncertainty, validation, and sensitivity testing and generates mean and standard deviation habitat suitability maps.}, } @article {pmid30680110, year = {2019}, author = {Lenormand, M and Papuga, G and Argagnon, O and Soubeyrand, M and De Barros, G and Alleaume, S and Luque, S}, title = {Biogeographical network analysis of plant species distribution in the Mediterranean region.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {237-250}, doi = {10.1002/ece3.4718}, pmid = {30680110}, issn = {2045-7758}, abstract = {The delimitation of bioregions helps to understand historical and ecological drivers of species distribution. In this work, we performed a network analysis of the spatial distribution patterns of plants in south of France (Languedoc-Roussillon and Provence-Alpes-Côte d'Azur) to analyze the biogeographical structure of the French Mediterranean flora at different scales. We used a network approach to identify and characterize biogeographical regions, based on a large database containing 2.5 million of geolocalized plant records corresponding to more than 3,500 plant species. This methodology is performed following five steps, from the biogeographical bipartite network construction to the identification of biogeographical regions under the form of spatial network communities, the analysis of their interactions, and the identification of clusters of plant species based on the species contribution to the biogeographical regions. First, we identified two sub-networks that distinguish Mediterranean and temperate biota. Then, we separated eight statistically significant bioregions that present a complex spatial structure. Some of them are spatially well delimited and match with particular geological entities. On the other hand, fuzzy transitions arise between adjacent bioregions that share a common geological setting, but are spread along a climatic gradient. The proposed network approach illustrates the biogeographical structure of the flora in southern France and provides precise insights into the relationships between bioregions. This approach sheds light on ecological drivers shaping the distribution of Mediterranean biota: The interplay between a climatic gradient and geological substrate shapes biodiversity patterns. Finally, this work exemplifies why fragmented distributions are common in the Mediterranean region, isolating groups of species that share a similar eco-evolutionary history.}, } @article {pmid30680109, year = {2019}, author = {Orgeret, F and Cox, SL and Weimerskirch, H and Guinet, C}, title = {Body condition influences ontogeny of foraging behavior in juvenile southern elephant seals.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {223-236}, doi = {10.1002/ece3.4717}, pmid = {30680109}, issn = {2045-7758}, abstract = {Ontogeny of diving and foraging behavior in marine top predators is poorly understood despite its importance in population recruitment. This lack of knowledge is partly due to the difficulties of monitoring juveniles in the wild, which is linked to high mortality early in life. Pinnipeds are good models for studying the development of foraging behaviors because juveniles are large enough to robustly carry tracking devices for many months. Moreover, parental assistance is absent after a juvenile departs for its first foraging trip, minimizing confounding effects of parental input on the development of foraging skills. In this study, we tracked 20 newly weaned juvenile southern elephant seals from Kerguelen Islands for up to 338 days during their first trip at sea following weaning. We used a new generation of satellite relay tags, which allow for the transmission of dive, accelerometer, and location data. We also monitored, at the same time, nine adult females from the colony during their post-breeding trips, in order to compare diving and foraging behaviors. Juveniles showed a gradual improvement through time in their foraging skills. Like adults females, they remarkably adjusted their swimming effort according to temporal changes in buoyancy (i.e., a proxy of their body condition). They also did not appear to exceed their aerobic physiological diving limits, although dives were constrained by their smaller size compared to adults. Changes in buoyancy appeared to also influence their decision to either keep foraging or return to land, alongside the duration of their haul outs and choice of foraging habitat (oceanic vs. plateau). Further studies are thus needed to better understand how patterns in juveniles survival, and therefore elephant seal populations, might be affected by their changes in foraging skills and changes in their environmental conditions.}, } @article {pmid30680108, year = {2019}, author = {Robertsen, G and Reid, D and Einum, S and Aronsen, T and Fleming, IA and Sundt-Hansen, LE and Karlsson, S and Kvingedal, E and Ugedal, O and Hindar, K}, title = {Can variation in standard metabolic rate explain context-dependent performance of farmed Atlantic salmon offspring?.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {212-222}, doi = {10.1002/ece3.4716}, pmid = {30680108}, issn = {2045-7758}, abstract = {Escaped farmed Atlantic salmon interbreed with wild Atlantic salmon, leaving offspring that often have lower success in nature than pure wild salmon. On top of this, presence of farmed salmon descendants can impair production of wild-type recruits. We hypothesize that both these effects connect with farmed salmon having acquired higher standard metabolic rates (SMR, the energetic cost of self-maintenance) during domestication. Fitness-related advantages of phenotypic traits associated with both high SMR and farmed salmon (e.g., social dominance) depend on environmental conditions, such as food availability. We hypothesize that farmed offspring have an advantage at high food availability due to, for example, dominance behavior but suffer increased risks of starvation when food is scarce because this behavior is energy-demanding. To test these hypotheses, we first compare embryo SMR of pure farmed, farmed-wild hybrids and pure wild offspring. Next, we test early-life performance (in terms of survival and growth) of hybrids relative to that of their wild half-siblings, as well as their competitive abilities, in semi-natural conditions of high and low food availability. Finally, we test how SMR affects early-life performance at high and low food availability. We find inconclusive support for the hypothesis that domestication has induced increased SMR. Further, wild and hybrid juveniles had similar survival and growth in the semi-natural streams. Yet, the presence of hybrids led to decreased survival of their wild half-siblings. Contrary to our hypothesis about context-dependency, these effects were not modified by food availability. However, wild juveniles with high SMR had decreased survival when food was scarce, but there was no such effect at high food availability. This study provides further proof that farmed salmon introgression may compromise the viability of wild salmon populations. We cannot, however, conclude that this is connected to alterations in the metabolic phenotype of farmed salmon.}, } @article {pmid30680107, year = {2019}, author = {Reum, JCP and Holsman, KK and Aydin, KY and Blanchard, JL and Jennings, S}, title = {Energetically relevant predator-prey body mass ratios and their relationship with predator body size.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {201-211}, doi = {10.1002/ece3.4715}, pmid = {30680107}, issn = {2045-7758}, abstract = {Food web structure and dynamics depend on relationships between body sizes of predators and their prey. Species-based and community-wide estimates of preferred and realized predator-prey mass ratios (PPMR) are required inputs to size-based size spectrum models of marine communities, food webs, and ecosystems. Here, we clarify differences between PPMR definitions in different size spectrum models, in particular differences between PPMR measurements weighting prey abundance in individual predators by biomass (rbio) and numbers (rnum). We argue that the former weighting generates PPMR as usually conceptualized in equilibrium (static) size spectrum models while the latter usually applies to dynamic models. We use diet information from 170,689 individuals of 34 species of fish in Alaskan marine ecosystems to calculate both PPMR metrics. Using hierarchical models, we examine how explained variance in these metrics changed with predator body size, predator taxonomic resolution, and spatial resolution. In the hierarchical analysis, variance in both metrics emerged primarily at the species level and substantially less variance was associated with other (higher) taxonomic levels or with spatial resolution. This suggests that changes in species composition are the main drivers of community-wide mean PPMR. At all levels of analysis, relationships between weighted mean rbio or weighted mean rnum and predator mass tended to be dome-shaped. Weighted mean rnum values, for species and community-wide, were approximately an order of magnitude higher than weighted mean rbio, reflecting the consistent numeric dominance of small prey in predator diets. As well as increasing understanding of the drivers of variation in PPMR and providing estimates of PPMR in the north Pacific Ocean, our results demonstrate that that rbio or rnum, as well as their corresponding weighted means for any defined group of predators, are not directly substitutable. When developing equilibrium size-based models based on bulk energy flux or comparing PPMR estimates derived from the relationship between body mass and trophic level with those based on diet analysis, weighted mean rbio is a more appropriate measure of PPMR. When calibrating preference PPMR in dynamic size spectrum models then weighted mean rnum will be a more appropriate measure of PPMR.}, } @article {pmid30680106, year = {2019}, author = {Brossette, L and Meunier, J and Dupont, S and Bagnères, AG and Lucas, C}, title = {Unbalanced biparental care during colony foundation in two subterranean termites.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {192-200}, doi = {10.1002/ece3.4710}, pmid = {30680106}, issn = {2045-7758}, abstract = {Parental care is a major component of reproduction in social organisms, particularly during the foundation steps. Because investment into parental care is often costly, each parent is predicted to maximize its fitness by providing less care than its partner. However, this sexual conflict is expected to be low in species with lifelong monogamy, because the fitness of each parent is typically tied to the other's input. Somewhat surprisingly, the outcomes of this tug-of-war between maternal and paternal investments have received important attention in vertebrate species, but remain less known in invertebrates. In this study, we investigated how queens and kings share their investment into parental care and other social interactions during colony foundation in two termites with lifelong monogamy: the invasive species Reticulitermes flavipes and the native species R. grassei. Behaviors of royal pairs were recorded during six months using a non-invasive approach. Our results showed that queens and kings exhibit unbalanced investment in terms of grooming, antennation, trophallaxis, and vibration behavior. Moreover, both parents show behavioral differences toward their partner or their descendants. Our results also revealed differences among species, with R. flavipes exhibiting shorter periods of grooming and antennation toward eggs or partners. They also did more stomodeal trophallaxis and less vibration behavior. Overall, this study emphasizes that despite lifelong monogamy, the two parents are not equally involved in the measured forms of parental care and suggests that kings might be specialized in other tasks. It also indicates that males could play a central, yet poorly studied role in the evolution and maintenance of the eusocial organization.}, } @article {pmid30680105, year = {2019}, author = {Bhattacharyya, S and Ishtiaq, F}, title = {Noninvasive sampling reveals population genetic structure in the Royle's pika, Ochotona roylei, in the western Himalaya.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {180-191}, doi = {10.1002/ece3.4707}, pmid = {30680105}, issn = {2045-7758}, abstract = {Understanding population genetic structure of climate-sensitive herbivore species is important as it provides useful insights on how shifts in environmental conditions can alter their distribution and abundance. Herbivore responses to the environment can have a strong indirect cascading effect on community structure. This is particularly important for Royle's pika (Lagomorpha: Ochotona roylei), a herbivorous talus-dwelling species in alpine ecosystem, which forms a major prey base for many carnivores in the Himalayan arc. In this study, we used seven polymorphic microsatellite loci to detect evidence for recent changes in genetic diversity and population structure in Royle's pika across five locations sampled between 8 and 160 km apart in the western Himalaya. Using four clustering approaches, we found the presence of significant contemporary genetic structure in Royle's pika populations. The detected genetic structure could be primarily attributed to the landscape features in alpine habitat (e.g., wide lowland valleys, rivers) that may act as semipermeable barriers to gene flow and distribution of food plants, which are key determinants in spatial distribution of herbivores. Pika showed low inbreeding coefficients (FIS) and a high level of pairwise relatedness for individuals within 1 km suggesting low dispersal abilities of talus-dwelling pikas. We have found evidence of a recent population bottleneck, possibly due to effects of environmental disturbances (e.g., snow melting patterns or thermal stress). Our results reveal significant evidence of isolation by distance in genetic differentiation (FST range = 0.04-0.19). This is the first population genetics study on Royle's pika, which helps to address evolutionary consequences of climate change which are expected to significantly affect the distribution and population dynamics in this talus-dwelling species.}, } @article {pmid30680104, year = {2019}, author = {Tapolczai, K and Vasselon, V and Bouchez, A and Stenger-Kovács, C and Padisák, J and Rimet, F}, title = {The impact of OTU sequence similarity threshold on diatom-based bioassessment: A case study of the rivers of Mayotte (France, Indian Ocean).}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {166-179}, doi = {10.1002/ece3.4701}, pmid = {30680104}, issn = {2045-7758}, abstract = {Extensive studies on the taxonomic resolution required for bioassessment purposes have determined that resolution above species level (genus, family) is sufficient for their use as indicators of relevant environmental pressures. The high-throughput sequencing (HTS) and meta-barcoding methods now used for bioassessment traditionally employ an arbitrary sequence similarity threshold (SST) around 95% or 97% to cluster sequences into operational taxonomic units, which is considered descriptive of species-level resolution. In this study, we analyzed the effect of the SST on the resulting diatom-based ecological quality index, which is based on OTU abundance distribution along a defined environmental gradient, ideally avoiding taxonomic assignments that could result in high rates of unclassified OTUs and biased final values. A total of 90 biofilm samples were collected in 2014 and 2015 from 51 stream sites on Mayotte Island in parallel with measures of relevant physical and chemical parameters. HTS sequencing was performed on the biofilms using the rbcL region as the genetic marker and diatom-specific primers. Hierarchical clustering was used to group sequences into OTUs using 20 experimental SST levels (80%-99%). An OTU-based quality index (IdxOTU) was developed based on a weighted average equation using the abundance profiles of the OTUs. The developed IdxOTU revealed significant correlations between the IdxOTU values and the reference pressure gradient, which reached maximal performance using an SST of 90% (well above species level delimitation). We observed an interesting and important trade-off with the power to discriminate between sampling sites and index stability that will greatly inform future applications of the index. Taken together, the results from this study detail a thoroughly optimized and validated approach to generating robust, reproducible, and complete indexes that will greatly facilitate effective and efficient environmental monitoring.}, } @article {pmid30680103, year = {2019}, author = {Dalerum, F and Retief, TA and Havemann, CP and Chimimba, CT and Janse van Rensburg, B}, title = {The influence of distance to perennial surface water on ant communities in Mopane woodlands, northern Botswana.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {154-165}, doi = {10.1002/ece3.4692}, pmid = {30680103}, issn = {2045-7758}, abstract = {Studies of biodiversity along environmental gradients provide information on how ecological communities change in response to biotic and abiotic factors. For instance, distance to water is associated with several factors that shape the structure and the functioning of ecosystems at a range of spatial scales. We investigated the influence of distance to a perennial water source on ant communities in a semi-arid savanna in northern Botswana. Ant abundance, taxonomic richness, and both alpha and beta diversity were generally higher during the wet than the dry season. However, there were strong seasonal influences on the effects of distance to water, with more pronounced effects during the wet season. While both abundance and beta diversity declined with increasing distances to water during the wet season, there was a contrasting increase in alpha diversity. There was no major effect of distance to water on taxonomic richness during either season. Beta diversity was as high across as along gradients, and we found support for modular rather than nested community structures along gradients. Our study demonstrated that small-scale gradients in distance to water can influence several aspects of ant communities in semi-arid savannas. However, our results also point to strong effects of small-scale environmental variation, for instance associated with vegetation characteristics, soil properties, and plant community structure that are not directly linked to water access.}, } @article {pmid30680102, year = {2019}, author = {Priadka, P and Manseau, M and Trottier, T and Hervieux, D and Galpern, P and McLoughlin, PD and Wilson, PJ}, title = {Partitioning drivers of spatial genetic variation for a continuously distributed population of boreal caribou: Implications for management unit delineation.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {141-153}, doi = {10.1002/ece3.4682}, pmid = {30680102}, issn = {2045-7758}, abstract = {Isolation by distance (IBD) is a natural pattern not readily incorporated into theoretical models nor traditional metrics for differentiating populations, although clinal genetic differentiation can be characteristic of many wildlife species. Landscape features can also drive population structure additive to baseline IBD resulting in differentiation through isolation-by-resistance (IBR). We assessed the population genetic structure of boreal caribou across western Canada using nonspatial (STRUCTURE) and spatial (MEMGENE) clustering methods and investigated the relative contribution of IBD and IBR on genetic variation of 1,221 boreal caribou multilocus genotypes across western Canada. We further introduced a novel approach to compare the partitioning of individuals into management units (MU) and assessed levels of genetic connectivity under different MU scenarios. STRUCTURE delineated five genetic clusters while MEMGENE identified finer-scale differentiation across the study area. IBD was significant and did not differ for males and females both across and among detected genetic clusters. MEMGENE landscape analysis further quantified the proportion of genetic variation contributed by IBD and IBR patterns, allowing for the relative importance of spatial drivers, including roads, water bodies, and wildfires, to be assessed and incorporated into the characterization of population structure for the delineation of MUs. Local population units, as currently delineated in the boreal caribou recovery strategy, do not capture the genetic variation and connectivity of the ecotype across the study area. Here, we provide the tools to assess fine-scale spatial patterns of genetic variation, partition drivers of genetic variation, and evaluate the best management options for maintaining genetic connectivity. Our approach is highly relevant to vagile wildlife species that are of management and conservation concern and demonstrate varying degrees of IBD and IBR with clinal spatial genetic structure that challenges the delineation of discrete population boundaries.}, } @article {pmid30680101, year = {2019}, author = {van der Loos, LM and Schmid, M and Leal, PP and McGraw, CM and Britton, D and Revill, AT and Virtue, P and Nichols, PD and Hurd, CL}, title = {Responses of macroalgae to CO2 enrichment cannot be inferred solely from their inorganic carbon uptake strategy.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {125-140}, doi = {10.1002/ece3.4679}, pmid = {30680101}, issn = {2045-7758}, abstract = {Increased plant biomass is observed in terrestrial systems due to rising levels of atmospheric CO2, but responses of marine macroalgae to CO2 enrichment are unclear. The 200% increase in CO2 by 2100 is predicted to enhance the productivity of fleshy macroalgae that acquire inorganic carbon solely as CO2 (non-carbon dioxide-concentrating mechanism [CCM] species-i.e., species without a carbon dioxide-concentrating mechanism), whereas those that additionally uptake bicarbonate (CCM species) are predicted to respond neutrally or positively depending on their affinity for bicarbonate. Previous studies, however, show that fleshy macroalgae exhibit a broad variety of responses to CO2 enrichment and the underlying mechanisms are largely unknown. This physiological study compared the responses of a CCM species (Lomentaria australis) with a non-CCM species (Craspedocarpus ramentaceus) to CO2 enrichment with regards to growth, net photosynthesis, and biochemistry. Contrary to expectations, there was no enrichment effect for the non-CCM species, whereas the CCM species had a twofold greater growth rate, likely driven by a downregulation of the energetically costly CCM(s). This saved energy was invested into new growth rather than storage lipids and fatty acids. In addition, we conducted a comprehensive literature synthesis to examine the extent to which the growth and photosynthetic responses of fleshy macroalgae to elevated CO2 are related to their carbon acquisition strategies. Findings highlight that the responses of macroalgae to CO2 enrichment cannot be inferred solely from their carbon uptake strategy, and targeted physiological experiments on a wider range of species are needed to better predict responses of macroalgae to future oceanic change.}, } @article {pmid30680100, year = {2019}, author = {Kärcher, O and Hering, D and Frank, K and Markovic, D}, title = {Freshwater species distributions along thermal gradients.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {111-124}, doi = {10.1002/ece3.4659}, pmid = {30680100}, issn = {2045-7758}, abstract = {The distribution of a species along a thermal gradient is commonly approximated by a unimodal response curve, with a characteristic single optimum near the temperature where a species is most likely to be found, and a decreasing probability of occurrence away from the optimum. We aimed at identifying thermal response curves (TRCs) of European freshwater species and evaluating the potential impact of climate warming across species, taxonomic groups, and latitude. We first applied generalized additive models using catchment-scale global data on distribution ranges of 577 freshwater species native to Europe and four different temperature variables (the current annual mean air/water temperature and the maximum air/water temperature of the warmest month) to describe species TRCs. We then classified TRCs into one of eight curve types and identified spatial patterns in thermal responses. Finally, we integrated empirical TRCs and the projected geographic distribution of climate warming to evaluate the effect of rising temperatures on species' distributions. For the different temperature variables, 390-463 of 577 species (67.6%-80.2%) were characterized by a unimodal TRC. The number of species with a unimodal TRC decreased from central toward northern and southern Europe. Warming tolerance (WT = maximum temperature of occurrence-preferred temperature) was higher at higher latitudes. Preferred temperature of many species is already exceeded. Rising temperatures will affect most Mediterranean species. We demonstrated that freshwater species' occurrence probabilities are most frequently unimodal. The impact of the global climate warming on species distributions is species and latitude dependent. Among the studied taxonomic groups, rising temperatures will be most detrimental to fish. Our findings support the efforts of catchment-based freshwater management and conservation in the face of global warming.}, } @article {pmid30680099, year = {2019}, author = {Leatherbury, KN and Travis, J}, title = {The effects of food level and social density on reproduction in the Least Killifish, Heterandria formosa.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {100-110}, doi = {10.1002/ece3.4634}, pmid = {30680099}, issn = {2045-7758}, abstract = {The feedbacks from population density to demographic parameters, which drive population regulation, are the accumulated results of several ecological processes. The compensatory feedback from increased population density to fertility includes at least two distinct factors, the effects of decreases in per capita food level and increases in the social density (the number of interacting individuals). Because these effects have been studied separately, their relative importance is unknown. It is also unclear whether food limitation and social density combine additively to influence fertility. We investigated these questions with two factorial experiments on reproduction in the Least Killifish, Heterandria formosa. In one experiment, we crossed two levels of density with two levels of a total food ration that was distributed to all individuals. In the other experiment, we crossed two levels of density with two levels of per capita food. Whereas the first experiment suggested that the effects of variation in food level and density were synergistic, the second experiment indicated that they were not. The apparent synergism-the statistical interaction of food and density levels-was the result of confounding per capita food with social density in that design. In the second experiment, the effects of social density on reproductive rate were stronger than the effects of food level, whereas the effects of food level were stronger on offspring size at parturition than those of social density. The results suggest that the social stresses that emerge at higher densities play an important role in the compensatory response of fertility to density, a role, that is, at least as important as that of decreased per capita food levels.}, } @article {pmid30680098, year = {2019}, author = {Bird, T and Lyon, J and Wotherspoon, S and Todd, C and Tonkin, Z and McCarthy, M}, title = {Combining capture-recapture data and known ages allows estimation of age-dependent survival rates.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {90-99}, doi = {10.1002/ece3.4633}, pmid = {30680098}, issn = {2045-7758}, abstract = {In many animal populations, demographic parameters such as survival and recruitment vary markedly with age, as do parameters related to sampling, such as capture probability. Failing to account for such variation can result in biased estimates of population-level rates. However, estimating age-dependent survival rates can be challenging because ages of individuals are rarely known unless tagging is done at birth. For many species, it is possible to infer age based on size. In capture-recapture studies of such species, it is possible to use a growth model to infer the age at first capture of individuals. We show how to build estimates of age-dependent survival into a capture-mark-recapture model based on data obtained in a capture-recapture study. We first show how estimates of age based on length increments closely match those based on definitive aging methods. In simulated analyses, we show that both individual ages and age-dependent survival rates estimated from simulated data closely match true values. With our approach, we are able to estimate the age-specific apparent survival rates of Murray and trout cod in the Murray River, Australia. Our model structure provides a flexible framework within which to investigate various aspects of how survival varies with age and will have extensions within a wide range of ecological studies of animals where age can be estimated based on size.}, } @article {pmid30680097, year = {2019}, author = {Loosen, AE and Morehouse, AT and Boyce, MS}, title = {Land tenure shapes black bear density and abundance on a multi-use landscape.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {73-89}, doi = {10.1002/ece3.4617}, pmid = {30680097}, issn = {2045-7758}, abstract = {Global biodiversity is decreasing rapidly. Parks and protected lands, while designed to conserve wildlife, often cannot provide the habitat protection needed for wide-ranging animals such as the American black bear (Ursus americanus). Conversely, private lands are often working landscapes (e.g., farming) that have high human footprints relative to protected lands. In southwestern Alberta, road densities are highest on private lands and black bears can be hunted year-round. On protected lands, road densities are lowest, and hunting is prohibited. On public lands under the jurisdiction of the provincial government (Crown lands), seasonal hunting is permitted. Population estimates are needed to calculate sustainable harvest levels and to monitor population trends. In our study area, there has never been a robust estimate of black bear density and spatial drivers of black bear density are poorly understood. We used non-invasive genetic sampling and indices of habitat productivity and human disturbance to estimate density and abundance for male and female black bears in 2013 and 2014 using two methods: spatially explicit capture-recapture (SECR) and resource-selection functions (RSF). Land tenure best explained spatial variation in black bear density. Black bear densities for females and males were highest on parkland and lowest on Crown lands. Sex ratios were female-biased on private lands, likely a result of lower harvests and movement of females out of areas with high male density. Synthesis and application: Both SECR and RSF methods clearly indicate spatial structuring of black bear density, with a strong influence based on how lands are managed. Land tenure influences the distribution of available foods and risk from humans. We emphasize the need for improved harvest reporting, particularly for non-licensed hunting on private land, to estimate the extent of black bear harvest mortality.}, } @article {pmid30680096, year = {2019}, author = {Bhardwaj, M and Soanes, K and Lahoz-Monfort, JJ and Lumsden, LF and van der Ree, R}, title = {Little evidence of a road-effect zone for nocturnal, flying insects.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {65-72}, doi = {10.1002/ece3.4609}, pmid = {30680096}, issn = {2045-7758}, abstract = {Roads and traffic may be contributing to global declines of insect populations. The ecological effects of roads often extend far into the surrounding habitat, over a distance known as the road-effect zone. The quality of habitat in the road-effect zone is generally degraded (e.g., due to edge effects, noise, light, and chemical pollution) and can be reflected in species presence, abundance, or demographic parameters. Road-effect zones have been quantified for some vertebrate species but are yet to be quantified for insects. Investigating the road-effect zone for insects will provide a better understanding of how roads impact ecosystems, which is particularly important given the role insects play as pollinators, predators, and prey for other species. We quantified the road-effect zone for nocturnal flying insects along three major freeways in agricultural landscapes in southeast Australia. We collected insects using light traps at six points along 2-km transects perpendicular to each highway (n = 17). We sorted the samples into order, and dried and weighed each order to obtain a measure of dry biomass. Using regression models within a Bayesian framework of inference, we estimated the change in biomass of each order with distance from the road, while accounting for environmental variables such as temperature, moon phase, and vegetation structure. The biomass of nine of the ten orders sampled did not change with distance from the freeway. Orthoptera (i.e., grasshoppers and crickets) was the only order whose biomass increased with distance from the freeway. From our findings, we suggest that the impacts of roads on insects are unlikely extending into the surrounding landscape over a distance of 2 km. Therefore, if there are impacts of roads on insects, these are more likely to be concentrated at the road itself, or on finer taxonomic scales such as family or genus level.}, } @article {pmid30680095, year = {2019}, author = {Hirota, SK and Miki, N and Yasumoto, AA and Yahara, T}, title = {UV bullseye contrast of Hemerocallis flowers attracts hawkmoths but not swallowtail butterflies.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {52-64}, doi = {10.1002/ece3.4604}, pmid = {30680095}, issn = {2045-7758}, abstract = {The color and patterns of animal-pollinated flowers are known to have effects on pollinator attraction. In this study, the relative importance of flower color and color contrast patterns on pollinator attraction was examined in two pollinator groups, swallowtail butterflies and hawkmoths using two Hemerocallis species; butterfly-pollinated H. fulva and hawkmoth-pollinated H. citrina, having reddish and yellowish flowers in human vision, respectively. Flowers of both species have UV bullseye patterns, composed of UV-absorbing centers and UV-reflecting peripheries, known to function as a typical nectar guide, but UV reflectance was significantly more intense in the peripheries of H. citrina flowers than in those of H. fulva flowers. Comparison based on the visual systems of butterflies and hawkmoths showed that the color contrast of the bullseye pattern in H. citrina was more intense than that in H. fulva. To evaluate the relative importance of flower color and the color contrast of bullseye pattern on pollinator attraction, we performed a series of observations using experimental arrays consisting of Hemerocallis species and their hybrids. As a result, swallowtail butterflies and crepuscular/nocturnal hawkmoths showed contrasting preferences for flower color and patterns: butterflies preferred H. fulva-like colored flower whereas the preference of hawkmoths was affected by the color contrast of the bullseye pattern rather than flower color. Both crepuscular and nocturnal hawkmoths consistently preferred flowers with stronger contrast of the UV bullseye pattern, whereas the preference of hawkmoths for flower color was incoherent. Our finding suggests that hawkmoths can use UV-absorbing/reflecting bullseye patterns for foraging under light-limited environments and that the intensified bullseye contrast of H. citrina evolved as an adaptation to hawkmoths. Our results also showed the difference of visual systems between pollinators, which may have promoted floral divergence.}, } @article {pmid30680094, year = {2019}, author = {Gotanda, KM and Pack, A and LeBlond, C and Hendry, AP}, title = {Do replicates of independent guppy lineages evolve similarly in a predator-free laboratory environment?.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {36-51}, doi = {10.1002/ece3.4585}, pmid = {30680094}, issn = {2045-7758}, abstract = {The Trinidadian guppy is emblematic of parallel and convergent evolution, with repeated demonstrations that predation regime is a driver of adaptive trait evolution. A classic and foundational experiment in this system was conducted by John Endler 40 years ago, where male guppies placed into low-predation environments in the laboratory evolved increased color in a few generations. However, Endler's experiment did not employ the now typical design for a parallel/convergent evolution study, which would employ replicates of different ancestral lineages. We therefore implemented an experiment that seeded replicate mesocosms with small founding populations of guppies originating from high-predation populations of two very different lineages. The different mesocosms were maintained identically, and male guppy color was quantified every four months. After one year, we tested whether male color had increased, whether replicates within a lineage had parallel phenotypic trajectories, and whether the different lineages converged on a common phenotype. Results showed that male guppy color generally increased through time, primarily due to changes in melanic color, whereas the other colors showed inconsistent and highly variable trajectories. Most of the nonparallelism in phenotypic trajectories was among mesocosms containing different lineages. In addition to this mixture of parallelism and nonparallelism, convergence was not evident in that the variance in color among the mesocosms actually increased through time. We suggest that our results reflect the potential importance of high variation in female preference and stochastic processes such as drift and founder effects, both of which could be important in nature.}, } @article {pmid30680093, year = {2019}, author = {Wang, Y and Rozen, DE}, title = {Fitness costs of phoretic nematodes in the burying beetle, Nicrophorus vespilloides.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {26-35}, doi = {10.1002/ece3.4570}, pmid = {30680093}, issn = {2045-7758}, abstract = {Nicrophorusvespilloides is a social beetle that rears its offspring on decomposing carrion. Wild beetles are frequently associated with two types of macrobial symbionts, mites, and nematodes. Although these organisms are believed to be phoretic commensals that harmlessly use beetles as a means of transfer between carcasses, the role of these symbionts on N. vespilloides fitness is poorly understood. Here, we show that nematodes have significant negative effects on beetle fitness across a range of worm densities and also quantify the density-dependent transmission of worms between mating individuals and from parents to offspring. Using field-caught beetles, we provide the first report of a new nematode symbiont in N. vespilloides, most closely related to Rhabditoides regina, and show that worm densities are highly variable across individuals isolated from nature but do not differ between males and females. Next, by inoculating mating females with increasing densities of nematodes, we show that worm infections significantly reduce brood size, larval survival, and larval mass, and also eliminate the trade-off between brood size and larval mass. Finally, we show that nematodes are efficiently transmitted between mating individuals and from mothers to larvae, directly and indirectly via the carcass, and that worms persist through pupation. These results show that the phoretic nematode R. regina can be highly parasitic to burying beetles but can nevertheless persist because of efficient mechanisms of intersexual and intergenerational transmission. Phoretic species are exceptionally common and may cause significant harm to their hosts, even though they rely on these larger species for transmission to new resources. However, this harm may be inevitable and unavoidable if transmission of phoretic symbionts requires nematode proliferation. It will be important to determine the generality of our results for other phoretic associates of animals. It will equally be important to assess the fitness effects of phoretic species under changing resource conditions and in the field where diverse interspecific interactions may exacerbate or reduce the negative effects of phoresy.}, } @article {pmid30680092, year = {2019}, author = {Davis, MJ and Andersen, JC and Elkinton, J}, title = {Identification of the parasitoid community associated with an outbreaking gall wasp, Zapatella davisae, and their relative abundances in New England and Long Island, New York.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {19-25}, doi = {10.1002/ece3.4543}, pmid = {30680092}, issn = {2045-7758}, abstract = {Gall wasps (Hymenoptera: Cynipidae) are phytophagous insects that often go unnoticed; however, when they are introduced to a new area or released from their natural enemies, they have the capacity to outbreak and cause extensive foliar damage. One such outbreaking pest, Zapatella davisae (Cynipidae: Cynipini), causes significant damage and mortality to black oak, Quercus velutina, in the northeastern United States. In this study, we aimed to identify the parasitoid community associated with Z. davisae, compare differences in percent parasitism of Z. davisae in Cape Cod and Long Island, and determine which parasitoid species contribute most to parasitism in each region. From both locations, we reared parasitoids, identified morphological groups, analyzed percent parasitism rates for each group, and used DNA barcoding to provide species-level identifications. On Long Island, there was nearly 100% parasitism in 2015 followed by a near total collapse of the population in 2016. In contrast, parasitism rates were lower and remained consistent on Cape Cod between 2015 and 2016, which may explain the greater canopy damage observed in that region. Species of Sycophila were the dominant parasitoids, with one species Sycophila nr. novascotiae representing ~65% of reared parasitoids from Long Island, and two species of Sycophila (S. nr. novascotiae and S. foliatae) with near equal representations on Cape Cod. In order to manage an insect pest, it is important to understand factors that influence its mortality and survival. An understanding of how these infestations progress overtime can help predict the impact that newer infestations in Nantucket, MA, and coastal Rhode Island will have on black oak populations and will aid in the management of this rapidly spreading gall wasp pest.}, } @article {pmid30680091, year = {2019}, author = {Singh, PB and Saud, P and Cram, D and Mainali, K and Thapa, A and Chhetri, NB and Poudyal, LP and Baral, HS and Jiang, Z}, title = {Ecological correlates of Himalayan musk deer Moschus leucogaster.}, journal = {Ecology and evolution}, volume = {9}, number = {1}, pages = {4-18}, doi = {10.1002/ece3.4435}, pmid = {30680091}, issn = {2045-7758}, abstract = {Himalayan musk deer (Moschus leucogaster; hereafter musk deer) are endangered as a result of poaching and habitat loss. The species is nocturnal, crepuscular, and elusive, making direct observation of habitat use and behavior difficult. However, musk deer establish and repeatedly use the same latrines for defecation. To quantify musk deer habitat correlates, we used observational spatial data based on presence-absence of musk deer latrines, as well as a range of fine spatial-scale ecological covariates. To determine presence-absence of musk deer, we exhaustively searched randomly selected forest trails using a 20-m belt transect in different study sites within the Neshyang Valley in the Annapurna Conservation Area. In a subsequent way, study sites were classified as habitat or nonhabitat for musk deer. A total of 252 plots, 20 × 20 m, were systematically established every 100 m along 51 transects (each ~0.5 km long) laid out at different elevations to record a range of ecological habitat variables. We used mixed-effect models and principal component analysis to characterize relationships between deer presence-absence data and habitat variables. We confirmed musk deer use latrines in forests located at higher elevations (3,200-4,200 m) throughout multiple seasons and years. Himalayan birch (Betula utilis) dominated forest, mixed Himalayan fir (Abies spectabilis), and birch forest were preferred over pure Himalayan fir and blue pine (Pinus wallichiana) forest. Greater crown cover and shrub diversity were associated with the presence of musk deer whereas tree height, diameter, and diversity were weakly correlated. Topographical attributes including aspect, elevation, distance to water source, and slope were also discriminated by musk deer. Over- and understory forest management can be used to protect forests likely to have musk deer as predicted by the models to ensure long-term conservation of this rare deer.}, } @article {pmid30661570, year = {2019}, author = {Gestal, MC and Whitesides, LT and Harvill, ET}, title = {Integrated Signaling Pathways Mediate Bordetella Immunomodulation, Persistence, and Transmission.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {118-130}, doi = {10.1016/j.tim.2018.09.010}, pmid = {30661570}, issn = {1878-4380}, support = {R21 AI116186/AI/NIAID NIH HHS/United States ; R56 AI107016/AI/NIAID NIH HHS/United States ; R01 GM113681/GM/NIGMS NIH HHS/United States ; R01 GM083113/GM/NIGMS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, abstract = {The mammalian immune system includes a sophisticated array of antimicrobial mechanisms. However, successful pathogens have developed subversive strategies to detect, modulate, and/or evade immune control and clearance. Independent disciplines study host immunology and bacterial pathogenesis, but interkingdom signaling between bacteria and host during natural infection remains poorly understood. An efficient natural host infection system has revealed complex communication between Bordetella spp. and mice, identified novel regulatory mechanisms, and demonstrated that bordetellae can respond to microenvironment and inflammatory status cues. Understanding these bacterial signaling pathways and their complex network that allows precisely timed expression of numerous immunomodulatory factors will serve as a paradigm for other organisms lacking such a powerful experimental infection system. VIDEO ABSTRACT.}, } @article {pmid30656826, year = {2018}, author = {Zhan, C and Liu, W and Hegazy, AM and Zhang, T and Kawan, A and Zhang, X}, title = {Explorations of the optimal method for isolating oocytes from zebrafish (Danio rerio) ovary.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {8}, pages = {417-426}, doi = {10.1002/jez.b.22841}, pmid = {30656826}, issn = {1552-5015}, support = {31670520//National Natural Science Foundation of China/ ; 42000481-7//Ministry of Science and Technology (MOST), Talent Young Scientist Program (TYSP)/ ; }, abstract = {Obtaining oocytes from the adult female zebrafish (Danio rerio) ovary has enormous importance in the studies of developmental biology, toxicology, and genetics. It is vital to establish a simple and effective approach to ensure the quantity and quality of oocytes, which will enable the success of follow-up experimental investigation finally. Usually, oocytes are separated with mechanical or enzymatic methods, however, little studies have been done with concerns about the comparative effects. The present study separated zebrafish oocytes of Stage III with five frequently used methods, including stripping, pipetting, hyaluronidase (1.6 mg/ml), collagenase (0.4 mg/ml), and trypsin (0.1%). The cell viability, oxidative stress, mitogen-activated protein kinase (MAPK) protein phosphorylation, and apoptosis levels were selected as main biomarkers to evaluate the oocytes health status. The results showed that both trypsin and hyaluronidase isolation significantly upregulated germinal vesicle breakdown (GVBD) rates and downregulated p38 MAPK activity simultaneously. GVBD rates and survival rates were decreased notably in oocytes separated by the collagenase method. Above results indicate that zebrafish oocytes in vitro are sensitive to enzymatic treatments and the enzymatic isolation is not the suitable mean for collecting zebrafish oocytes although it is time-saving. The mechanical strategy of pipetting remarkably increased the reactive oxygen species and malondialdehyde level in isolated oocytes. Interestingly, oocytes separated with stripping show less physiological and biochemical damages. Therefore, stripping isolation is comparatively recommended as the optimum method for separating and collecting numerous intact and healthy zebrafish oocytes in vitro for the subsequent developmental research.}, } @article {pmid30647475, year = {2019}, author = {Rojas-Bracho, L and Brusca, RC and Álvarez-Borrego, S and Brownell, RL and Camacho-Ibar, V and Ceballos, G and de la Cueva, H and García-Hernández, J and Hastings, PA and Cárdenas-Hinojosa, G and Jaramillo-Legorreta, AM and Medellín, R and Mesnick, SL and Nieto-García, E and Urbán, J and Velarde, E and Vidal, O and Findley, LT and Taylor, BL}, title = {Unsubstantiated Claims Can Lead to Tragic Conservation Outcomes.}, journal = {Bioscience}, volume = {69}, number = {1}, pages = {12-14}, doi = {10.1093/biosci/biy138}, pmid = {30647475}, issn = {0006-3568}, } @article {pmid30644436, year = {2018}, author = {Wu, X and Cabanos, C and Rapoport, TA}, title = {Structure of the post-translational protein translocation machinery of the ER membrane.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41586-018-0856-x}, pmid = {30644436}, issn = {1476-4687}, support = {R01 GM052586/GM/NIGMS NIH HHS/United States ; }, abstract = {Many proteins must translocate through the protein-conducting Sec61 channel in the eukaryotic endoplasmic reticulum membrane or the SecY channel in the prokaryotic plasma membrane1,2. Proteins with highly hydrophobic signal sequences are first recognized by the signal recognition particle (SRP)3,4 and then moved co-translationally through the Sec61 or SecY channel by the associated translating ribosome. Substrates with less hydrophobic signal sequences bypass the SRP and are moved through the channel post-translationally5,6. In eukaryotic cells, post-translational translocation is mediated by the association of the Sec61 channel with another membrane protein complex, the Sec62-Sec63 complex7-9, and substrates are moved through the channel by the luminal BiP ATPase9. How the Sec62-Sec63 complex activates the Sec61 channel for post-translational translocation is not known. Here we report the electron cryo-microscopy structure of the Sec complex from Saccharomyces cerevisiae, consisting of the Sec61 channel and the Sec62, Sec63, Sec71 and Sec72 proteins. Sec63 causes wide opening of the lateral gate of the Sec61 channel, priming it for the passage of low-hydrophobicity signal sequences into the lipid phase, without displacing the channel's plug domain. Lateral channel opening is triggered by Sec63 interacting both with cytosolic loops in the C-terminal half of Sec61 and transmembrane segments in the N-terminal half of the Sec61 channel. The cytosolic Brl domain of Sec63 blocks ribosome binding to the channel and recruits Sec71 and Sec72, positioning them for the capture of polypeptides associated with cytosolic Hsp7010. Our structure shows how the Sec61 channel is activated for post-translational protein translocation.}, } @article {pmid30637919, year = {2018}, author = {Holthaus, KB and Eckhart, L and Dalla Valle, L and Alibardi, L}, title = {Review: Evolution and diversification of corneous beta-proteins, the characteristic epidermal proteins of reptiles and birds.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {8}, pages = {438-453}, doi = {10.1002/jez.b.22840}, pmid = {30637919}, issn = {1552-5015}, abstract = {In all amniotes specialized intermediate filament keratins (IF-keratins), in addition to keratin-associated and corneous proteins form the outermost cornified layer of the epidermis. Only in reptiles and birds (sauropsids) the epidermis of scales, claws, beaks, and feathers, largely comprises small proteins formerly indicated as "beta-keratins" but here identified as corneous beta-proteins (CBPs) to avoid confusion with true keratins. Genes coding for CBPs have evolved within the epidermal differentiation complex (EDC), a locus with no relationship with those of IF-keratins. CBP genes have the same exon-intron structure as EDC genes encoding other corneous proteins of sauropsids and mammals, but they are unique by encoding a peculiar internal amino acid sequence motif beta-sheet region that allows formation of CBP filaments in the epidermis and epidermal appendages of reptiles and birds. In contrast, skin appendages of mammals, like hairs, claws, horns and nails, contain keratin-associated proteins that, like IF-keratin genes, are encoded by genes in loci different from the EDC. Phylogenetic analysis shows that lepidosaurian (lizards and snakes) and nonlepidosaurian (crocodilians, birds, and turtles) CBPs form two separate clades that likely originated after the divergence of these groups of sauropsids in the Permian Period. Clade-specific CBPs evolved to make most of the corneous material of feathers in birds and of the shell in turtles. Based on the recent identification of the complete sets of CBPs in all major phylogenetic clades of sauropsids, this review provides a comprehensive overview of the molecular evolution of CBPs.}, } @article {pmid30626996, year = {2018}, author = {Kume, K and Amagasa, T and Hashimoto, T and Kitagawa, H}, title = {NommPred: Prediction of Mitochondrial and Mitochondrion-Related Organelle Proteins of Nonmodel Organisms.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318819835}, doi = {10.1177/1176934318819835}, pmid = {30626996}, issn = {1176-9343}, abstract = {To estimate the functions of mitochondria of diverse eukaryotic nonmodel organisms in which the mitochondrial proteomes are not available, it is necessary to predict the protein sequence features of the mitochondrial proteins computationally. Various prediction methods that are trained using the proteins of model organisms belonging particularly to animals, plants, and fungi exist. However, such methods may not be suitable for predicting the proteins derived from nonmodel organisms because the sequence features of the mitochondrial proteins of diversified nonmodel organisms can differ from those of model organisms that are present only in restricted parts of the tree of eukaryotes. Here, we proposed NommPred, which predicts the mitochondrial proteins of nonmodel organisms that are widely distributed over eukaryotes. We used a gradient boosting machine to develop 2 predictors-one for predicting the proteins of mitochondria and the other for predicting the proteins of mitochondrion-related organelles that are highly reduced mitochondria. The performance of both predictors was found to be better than that of the best method available.}, } @article {pmid30626964, year = {2019}, author = {Wilkinson, AW and Diep, J and Dai, S and Liu, S and Ooi, YS and Song, D and Li, TM and Horton, JR and Zhang, X and Liu, C and Trivedi, DV and Ruppel, KM and Vilches-Moure, JG and Casey, KM and Mak, J and Cowan, T and Elias, JE and Nagamine, CM and Spudich, JA and Cheng, X and Carette, JE and Gozani, O}, title = {SETD3 is an actin histidine methyltransferase that prevents primary dystocia.}, journal = {Nature}, volume = {565}, number = {7739}, pages = {372-376}, doi = {10.1038/s41586-018-0821-8}, pmid = {30626964}, issn = {1476-4687}, support = {DP2 AI104557/AI/NIAID NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; }, abstract = {For more than 50 years, the methylation of mammalian actin at histidine 73 has been known to occur1. Despite the pervasiveness of His73 methylation, which we find is conserved in several model animals and plants, its function remains unclear and the enzyme that generates this modification is unknown. Here we identify SET domain protein 3 (SETD3) as the physiological actin His73 methyltransferase. Structural studies reveal that an extensive network of interactions clamps the actin peptide onto the surface of SETD3 to orient His73 correctly within the catalytic pocket and to facilitate methyl transfer. His73 methylation reduces the nucleotide-exchange rate on actin monomers and modestly accelerates the assembly of actin filaments. Mice that lack SETD3 show complete loss of actin His73 methylation in several tissues, and quantitative proteomics analysis shows that actin His73 methylation is the only detectable physiological substrate of SETD3. SETD3-deficient female mice have severely decreased litter sizes owing to primary maternal dystocia that is refractory to ecbolic induction agents. Furthermore, depletion of SETD3 impairs signal-induced contraction in primary human uterine smooth muscle cells. Together, our results identify a mammalian histidine methyltransferase and uncover a pivotal role for SETD3 and actin His73 methylation in the regulation of smooth muscle contractility. Our data also support the broader hypothesis that protein histidine methylation acts as a common regulatory mechanism.}, } @article {pmid30624113, year = {2019}, author = {Abdelaziz, M and Bakkali, M and Gómez, JM and Olivieri, E and Perfectti, F}, title = {Anther Rubbing, a New Mechanism That Actively Promotes Selfing in Plants.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {140-147}, doi = {10.1086/700875}, pmid = {30624113}, issn = {1537-5323}, abstract = {Self-fertilization has recurrently evolved in plants, involving different strategies and traits and often loss of attractive functions, collectively known as the selfing syndrome. However, few traits that actively promote self-fertilization have been described. Here we describe a novel mechanism promoting self-fertilization in the Brassicaceae species Erysimum incanum. This mechanism, which we called "anther rubbing," consists of autonomous, repeated, and coordinated movements of the stamens over the stigma during flower opening. We have documented anther rubbing by time-lapse videos and experimentally show that it causes self-pollen deposition on stigmas and is sufficient to achieve maximal reproductive output in E. incanum. We predict that these movements should occur in species with limited inbreeding depression, and indeed we find that inbreeding depression in seed production is negligible in this species. While many studies have documented complex floral traits that promote outcrossing, the occurrence of anther rubbing demonstrates that plants can evolve elaborate and underappreciated adaptations to promote self-fertilization.}, } @article {pmid30624112, year = {2019}, author = {Backmann, P and Grimm, V and Jetschke, G and Lin, Y and Vos, M and Baldwin, IT and van Dam, NM}, title = {Delayed Chemical Defense: Timely Expulsion of Herbivores Can Reduce Competition with Neighboring Plants.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {125-139}, doi = {10.1086/700577}, pmid = {30624112}, issn = {1537-5323}, abstract = {Time delays in plant responses to insect herbivory are thought to be the principal disadvantage of induced over constitutive defenses, suggesting that there should be strong selection for rapid responses. However, observed time delays between the onset of herbivory and defense induction vary considerably among plants. We postulate that strong competition with conspecifics is an important codeterminant of the cost-benefit balance for induced responses. There may be a benefit to the plant to delay mounting a full defense response until the herbivore larvae are mobile enough to leave and large enough to cause severe damage to neighboring plants. Thus, delayed responses could reduce the competitive pressure on the focal plant. To explore this idea, we developed an individual-based model using data from wild tobacco, Nicotiana attenuata, and its specialized herbivore, Manduca sexta. Chemical defense was assumed to be costly in terms of reduced plant growth. We used a genetic algorithm with the plant's delay time as a heritable trait. A stationary distribution of delay times emerged, which under high herbivore densities peaked at higher values, which were related to the time larvae need to grow large enough to severely damage neighboring plants. Plants may thus tip the competitive balance by expelling insect herbivores to move to adjacent plants when the herbivores are most damaging. Thus, herbivores become part of a plant's strategy for reducing competition and increasing fitness.}, } @article {pmid30624111, year = {2019}, author = {Wardlaw, AM and Agrawal, AF}, title = {Sexual Conflict and Sexually Transmitted Infections (STIs): Coevolution of Sexually Antagonistic Host Traits with an STI.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {E1-E14}, doi = {10.1086/700564}, pmid = {30624111}, issn = {1537-5323}, abstract = {In many taxa, there is a conflict between the sexes over mating rate. The outcome of sexually antagonistic coevolution depends on the costs of mating and natural selection against sexually antagonistic traits. A sexually transmitted infection (STI) changes the relative strength of these costs. We study the three-way evolutionary interaction among male persistence, female resistance, and STI virulence for two types of STIs: a viability-reducing STI and a reproduction-reducing STI. A viability-reducing STI escalates conflict between the sexes. This leads to increased STI virulence (i.e., full coevolution) if the costs of sexually antagonistic traits occur through viability but not through reproduction. In contrast, a reproduction-reducing STI de-escalates the sexual conflict, but STI virulence does not coevolve in response. We also investigated the establishment probability of STIs under different combinations of evolvability. Successful invasion by a viability-reducing STI becomes less likely if hosts (but not parasites) are evolvable, especially if only the female trait can evolve. A reproduction-reducing STI can almost always invade because it does not kill its host. We discuss how the evolution of host and parasite traits in a system with sexual conflict differs from a system with female mate choice.}, } @article {pmid30624110, year = {2019}, author = {Ferrari, M and Lindholm, AK and König, B}, title = {Fitness Consequences of Female Alternative Reproductive Tactics in House Mice (Mus musculus domesticus).}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {106-124}, doi = {10.1086/700567}, pmid = {30624110}, issn = {1537-5323}, abstract = {Alternative reproductive tactics (ARTs) are defined as discrete differences in morphological, physiological, and/or behavioral traits associated with reproduction that occur within the same sex and population. House mice provide a rare example of ARTs in females, which can rear their young either solitarily or together with one or several other females in a communal nest. We assessed the fitness consequences of communal and solitary breeding in a wild population to understand how the two tactics can be evolutionarily stable. Females switched between the two tactics (with more than 50% of all females having two or more litters using both tactics), pointing toward communal and solitary breeding being two tactics within a single strategy and not two genetically determined strategies. Communal breeding resulted in reduced pup survival and negatively impacted female reproductive success. Older and likely heavier females more often reared their litters solitarily, indicating that females use a condition-dependent strategy. Solitary breeding seems the more successful tactic, and only younger and likely less competitive females might opt for communal nursing, even at the cost of increased pup mortality. This study emphasizes the importance of analyzing phenotypic plasticity and its role in cooperation in the context of female ARTs.}, } @article {pmid30624109, year = {2019}, author = {Gouveia, SF and Bovo, RP and Rubalcaba, JG and Da Silva, FR and Maciel, NM and Andrade, DV and Martinez, PA}, title = {Biophysical Modeling of Water Economy Can Explain Geographic Gradient of Body Size in Anurans.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {51-58}, doi = {10.1086/700833}, pmid = {30624109}, issn = {1537-5323}, abstract = {Geographical gradients of body size express climate-driven constraints on animals, but whether they exist and what causes them in ectotherms remains contentious. For amphibians, the water conservation hypothesis posits that larger bodies reduce evaporative water loss (EWL) along dehydrating gradients. To address this hypothesis mechanistically, we build on well-established biophysical equations of water exchange in anurans to propose a state-transition model that predicts an increase of either body size or resistance to EWL as alternative specialization along dehydrating gradients. The model predicts that species whose water economy is more sensitive to variation in body size than to variation in resistance to EWL should increase in size in response to increasing potential evapotranspiration (PET). To evaluate the model predictions, we combine physiological measurements of resistance to EWL with geographic data of body size for four different anuran species. Only one species, Dendropsophus minutus, was predicted to exhibit a positive body size-PET relationship. Results were as predicted for all cases, with one species-Boana faber-showing a negative relationship. Based on an empirically verified mathematical model, we show that clines of body size among anurans depend on the current values of those traits and emerge as an advantage for water conservation. Our model offers a mechanistic and compelling explanation for the cause and variation of gradients of body size in anurans.}, } @article {pmid30624108, year = {2019}, author = {}, title = {2018 American Society of Naturalists Awards.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {ii-iii}, doi = {10.1086/700876}, pmid = {30624108}, issn = {1537-5323}, } @article {pmid30624107, year = {2019}, author = {Hahn, PG and Agrawal, AA and Sussman, KI and Maron, JL}, title = {Population Variation, Environmental Gradients, and the Evolutionary Ecology of Plant Defense against Herbivory.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {20-34}, doi = {10.1086/700838}, pmid = {30624107}, issn = {1537-5323}, abstract = {A central tenet of plant defense theory is that adaptation to the abiotic environment sets the template for defense strategies, imposing a trade-off between plant growth and defense. Yet this trade-off, commonly found among species occupying divergent resource environments, may not occur across populations of single species. We hypothesized that more favorable climates and higher levels of herbivory would lead to increases in growth and defense across plant populations. We evaluated whether plant growth and defense traits covaried across 18 populations of showy milkweed (Asclepias speciosa) inhabiting an east-west climate gradient spanning 25° of longitude. A suite of traits impacting defense (e.g., latex, cardenolides), growth (e.g., size), or both (e.g., specific leaf area [SLA], trichomes) were measured in natural populations and in a common garden, allowing us to evaluate plastic and genetically based variation in these traits. In natural populations, herbivore pressure increased toward warmer sites with longer growing seasons. Growth and defense traits showed strong clinal patterns and were positively correlated. In a common garden, clines with climatic origin were recapitulated only for defense traits. Correlations between growth and defense traits were also weaker and more negative in the common garden than in the natural populations. Thus, our data suggest that climatically favorable sites likely facilitate the evolution of greater defense at minimal costs to growth, likely because of increased resource acquisition.}, } @article {pmid30624106, year = {2019}, author = {Patin, R and Fortin, D and Sueur, C and Chamaillé-Jammes, S}, title = {Space Use and Leadership Modify Dilution Effects on Optimal Vigilance under Food-Safety Trade-Offs.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {E15-E28}, doi = {10.1086/700566}, pmid = {30624106}, issn = {1537-5323}, abstract = {Dilution of predation risk within groups allows individuals to be less vigilant and forage more while still facing lower risk than if they were alone. How group size influences vigilance when individuals can also adjust their space use and whether this relationship differs among individuals contributing differently to space use decisions remain unknown. We present a model-based study of how dilution affects the optimal antipredator behavior of group members in groups where all individuals determine their vigilance level while group leaders also determine space use. We showed that optimal vigilance did not always decrease with group size, as it was sometimes favorable for individuals in larger groups to use riskier patches while remaining vigilant. Followers were also generally less vigilant than leaders. Indeed, followers needed to acquire more resources than leaders, as only the latter could decide when to go to richer patches. Followers still benefit from dilution of predation risk compared with solitary individuals. For leaders, keeping their leadership status can be more important than incorporating new group members to increase dilution. We demonstrate that risk dilution impacts both optimal vigilance and space use, with fitness reward being tied to a member's ability to influence group space use.}, } @article {pmid30624105, year = {2019}, author = {Webb, MH and Heinsohn, R and Sutherland, WJ and Stojanovic, D and Terauds, A}, title = {An Empirical and Mechanistic Explanation of Abundance-Occupancy Relationships for a Critically Endangered Nomadic Migrant.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {59-69}, doi = {10.1086/700595}, pmid = {30624105}, issn = {1537-5323}, abstract = {The positive abundance-occupancy relationship (AOR) is a pervasive pattern in macroecology. Similarly, the association between occupancy (or probability of occurrence) and abundance is also usually assumed to be positive and in most cases constant. Examples of AORs for nomadic species with variable distributions are extremely rare. Here we examined temporal and spatial trends in the AOR over 7 years for a critically endangered nomadic migrant that relies on dynamic pulses in food availability to breed. We predicted a negative temporal relationship, where local mean abundances increase when the number of occupied sites decreases, and a positive relationship between local abundances and the probability of occurrence. We also predicted that these patterns are largely attributable to spatiotemporal variation in food abundance. The temporal AOR was significantly negative, and annual food availability was significantly positively correlated with the number of occupied sites but negatively correlated with abundance. Thus, as food availability decreased, local densities of birds increased, and vice versa. The abundance-probability of occurrence relationship was positive and nonlinear but varied between years due to differing degrees of spatial aggregation caused by changing food availability. Importantly, high abundance (or occupancy) did not necessarily equate to high-quality habitat and may be indicative of resource bottlenecks or exposure to other processes affecting vital rates. Our results provide a rare empirical example that highlights the complexity of AORs for species that target aggregated food resources in dynamic environments.}, } @article {pmid30624104, year = {2019}, author = {Leimar, O and Dall, SRX and McNamara, JM and Kuijper, B and Hammerstein, P}, title = {Ecological Genetic Conflict: Genetic Architecture Can Shift the Balance between Local Adaptation and Plasticity.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {70-80}, doi = {10.1086/700719}, pmid = {30624104}, issn = {1537-5323}, abstract = {Genetic polymorphism can contribute to local adaptation in heterogeneous habitats, for instance, as a single locus with alleles adapted to different habitats. Phenotypic plasticity can also contribute to trait variation across habitats, through developmental responses to habitat-specific cues. We show that the genetic architecture of genetically polymorphic and plasticity loci may influence the balance between local adaptation and phenotypic plasticity. These effects of genetic architecture are instances of ecological genetic conflict. A reduced effective migration rate for genes tightly linked to a genetic polymorphism provides an explanation for the effects, and they can occur both for a single trait and for a syndrome of coadapted traits. Using individual-based simulations and numerical analysis, we investigate how among-habitat genetic polymorphism and phenotypic plasticity depend on genetic architecture. We also study the evolution of genetic architecture itself, in the form of rates of recombination between genetically polymorphic loci and plasticity loci. Our main result is that for plasticity genes that are unlinked to loci with between-habitat genetic polymorphism, the slope of a reaction norm is steeper in comparison with the slope favored by plasticity genes that are tightly linked to genes for local adaptation.}, } @article {pmid30624103, year = {2019}, author = {Yeh, DJ}, title = {Assortative Mating by an Obliquely Transmitted Local Cultural Trait Promotes Genetic Divergence: A Model.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {81-92}, doi = {10.1086/700958}, pmid = {30624103}, issn = {1537-5323}, abstract = {The effect of learned culture (e.g., birdsong dialects and human languages) on genetic divergence is unclear. Previous theoretical research suggests that because oblique learning allows phenotype transmission from individuals with no offspring to an unrelated individual in the next generation, the effect of sexual selection on the learned trait is masked. However, I propose that migration and spatially constrained learning can form statistical associations between cultural and genetic traits, which may allow selection on the cultural traits to indirectly affect the genetic traits. Here, I build a population genetic model that allows such statistical associations to form and find that sexual selection and divergent selection on the cultural trait can indeed help maintain genetic divergence through such statistical associations, while selection against genetic hybrids does not affect cultural trait divergence. Furthermore, I find that even when the cultural trait changes over time due to drift and mutation, it can still help maintain genetic divergence. These results suggest the role of obliquely transmitted traits in evolution may be underrated, and the lack of one-to-one associations between cultural and genetic traits may not be sufficient to disprove the role of culture in genetic divergence.}, } @article {pmid30624102, year = {2019}, author = {Connallon, T and Sharma, S and Olito, C}, title = {Evolutionary Consequences of Sex-Specific Selection in Variable Environments: Four Simple Models Reveal Diverse Evolutionary Outcomes.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {93-105}, doi = {10.1086/700720}, pmid = {30624102}, issn = {1537-5323}, abstract = {The evolutionary trajectories of species with separate sexes depend on the effects of genetic variation on female and male traits as well as the direction and alignment of selection between the sexes. Classical theory has shown that evolution is equally responsive to selection on females and males, with natural selection increasing the product of the average relative fitness of each sex over time. This simple rule underlies several important predictions regarding the maintenance of genetic variation, the genetic basis of adaptation, and the dynamics of "sexually antagonistic" alleles. Nevertheless, theories of sex-specific selection overwhelmingly focus on evolution in constant environments, and it remains unclear whether they apply under changing conditions. We derived four simple models of sex-specific selection in variable environments and explored how conditions of population subdivision, the timing of dispersal, sex differences in dispersal, and the nature of environmental change mediate the evolutionary dynamics of sex-specific adaptation. We find that these dynamics are acutely sensitive to ecological, demographic, and life-history attributes that vary widely among species, with classical predictions breaking down in contexts of environmental heterogeneity. The evolutionary rules governing sex-specific adaptation may therefore differ between species, suggesting new avenues for research on the evolution of sexual dimorphism.}, } @article {pmid30624101, year = {2019}, author = {Stuart, YE}, title = {Divergent Uses of "Parallel Evolution" during the History of The American Naturalist.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {11-19}, doi = {10.1086/700718}, pmid = {30624101}, issn = {1537-5323}, abstract = {The mechanistic link between natural selection and parallel evolution is well established. Natural selection is the only known deterministic process that can regularly overcome chance and historical contingency to generate the evolution of similar characteristics in independent populations inhabiting similar environments. However, the ready inference of natural selection from parallel evolution has been established only relatively recently. Here, I review the use of "parallel evolution" in the first 125 years of The American Naturalist and show that there were other well-accepted definitions of the term through the history of the field. I discuss the legacy of those alternative ideas and how they helped to shape evolution and ecology as we know them today and finish by discussing a geometric use for "parallel" that may reduce terminological confusion.}, } @article {pmid30624100, year = {2019}, author = {Shaw, RG}, title = {From the Past to the Future: Considering the Value and Limits of Evolutionary Prediction.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {1-10}, doi = {10.1086/700565}, pmid = {30624100}, issn = {1537-5323}, abstract = {The complex interplay of the multiple genetic processes of evolution and the ecological contexts in which they proceed frustrates detailed identification of many of the states of populations, both past and future, that may be of interest. Prediction of rates of adaptation, in the sense of change in mean fitness, into the future would, however, valuably inform expectations for persistence of populations, especially in our era of rapid environmental change. Heavy investment in genomics and other molecular tools has fueled belief that those approaches can effectively predict adaptation into the future. I contest this view. Genome scans display the genomic footprints of the effects of natural selection and the other evolutionary processes over past generations, but it remains problematic to predict future change in mean fitness via genomic approaches. Here, I advocate for a direct approach to prediction of rates of ongoing adaptation. Following an overview of relevant quantitative genetic approaches, I outline the promise of the fundamental theorem of natural selection for the study of the adaptive process. Empirical implementation of this concept can productively guide efforts both to deepen scientific insight into the process of adaptation and to inform measures for conserving the biota in the face of rapid environmental change.}, } @article {pmid30622641, year = {2019}, author = {López, ME and Benestan, L and Moore, JS and Perrier, C and Gilbey, J and Di Genova, A and Maass, A and Diaz, D and Lhorente, JP and Correa, K and Neira, R and Bernatchez, L and Yáñez, JM}, title = {Comparing genomic signatures of domestication in two Atlantic salmon (Salmo salar L.) populations with different geographical origins.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {137-156}, doi = {10.1111/eva.12689}, pmid = {30622641}, issn = {1752-4571}, abstract = {Selective breeding and genetic improvement have left detectable signatures on the genomes of domestic species. The elucidation of such signatures is fundamental for detecting genomic regions of biological relevance to domestication and improving management practices. In aquaculture, domestication was carried out independently in different locations worldwide, which provides opportunities to study the parallel effects of domestication on the genome of individuals that have been selected for similar traits. In this study, we aimed to detect potential genomic signatures of domestication in two independent pairs of wild/domesticated Atlantic salmon populations of Canadian and Scottish origins, respectively. Putative genomic regions under divergent selection were investigated using a 200K SNP array by combining three different statistical methods based either on allele frequencies (LFMM, Bayescan) or haplotype differentiation (Rsb). We identified 337 and 270 SNPs potentially under divergent selection in wild and hatchery populations of Canadian and Scottish origins, respectively. We observed little overlap between results obtained from different statistical methods, highlighting the need to test complementary approaches for detecting a broad range of genomic footprints of selection. The vast majority of the outliers detected were population-specific but we found four candidate genes that were shared between the populations. We propose that these candidate genes may play a role in the parallel process of domestication. Overall, our results suggest that genetic drift may have override the effect of artificial selection and/or point toward a different genetic basis underlying the expression of similar traits in different domesticated strains. Finally, it is likely that domestication may predominantly target polygenic traits (e.g., growth) such that its genomic impact might be more difficult to detect with methods assuming selective sweeps.}, } @article {pmid30622640, year = {2019}, author = {Pitt, D and Sevane, N and Nicolazzi, EL and MacHugh, DE and Park, SDE and Colli, L and Martinez, R and Bruford, MW and Orozco-terWengel, P}, title = {Domestication of cattle: Two or three events?.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {123-136}, doi = {10.1111/eva.12674}, pmid = {30622640}, issn = {1752-4571}, abstract = {Cattle have been invaluable for the transition of human society from nomadic hunter-gatherers to sedentary farming communities throughout much of Europe, Asia and Africa since the earliest domestication of cattle more than 10,000 years ago. Although current understanding of relationships among ancestral populations remains limited, domestication of cattle is thought to have occurred on two or three occasions, giving rise to the taurine (Bos taurus) and indicine (Bos indicus) species that share the aurochs (Bos primigenius) as common ancestor ~250,000 years ago. Indicine and taurine cattle were domesticated in the Indus Valley and Fertile Crescent, respectively; however, an additional domestication event for taurine in the Western Desert of Egypt has also been proposed. We analysed medium density Illumina Bovine SNP array (~54,000 loci) data across 3,196 individuals, representing 180 taurine and indicine populations to investigate population structure within and between populations, and domestication and demographic dynamics using approximate Bayesian computation (ABC). Comparative analyses between scenarios modelling two and three domestication events consistently favour a model with only two episodes and suggest that the additional genetic variation component usually detected in African taurine cattle may be explained by hybridization with local aurochs in Africa after the domestication of taurine cattle in the Fertile Crescent. African indicine cattle exhibit high levels of shared genetic variation with Asian indicine cattle due to their recent divergence and with African taurine cattle through relatively recent gene flow. Scenarios with unidirectional or bidirectional migratory events between European taurine and Asian indicine cattle are also plausible, although further studies are needed to disentangle the complex human-mediated dispersion patterns of domestic cattle. This study therefore helps to clarify the effect of past demographic history on the genetic variation of modern cattle, providing a basis for further analyses exploring alternative migratory routes for early domestic populations.}, } @article {pmid30622639, year = {2019}, author = {Pitt, D and Bruford, MW and Barbato, M and Orozco-terWengel, P and Martínez, R and Sevane, N}, title = {Demography and rapid local adaptation shape Creole cattle genome diversity in the tropics.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {105-122}, doi = {10.1111/eva.12641}, pmid = {30622639}, issn = {1752-4571}, abstract = {The introduction of Iberian cattle in the Americas after Columbus' arrival imposed high selection pressures on a limited number of animals over a brief period of time. Knowledge of the genomic regions selected during this process may help in enhancing climatic resilience and sustainable animal production. We first determined taurine and indicine contributions to the genomic structure of modern Creole cattle. Second, we inferred their demographic history using approximate Bayesian computation (ABC), linkage disequilibrium (LD) and Ne Slope (NeS) analysis. Third, we performed whole genome scans for selection signatures based on cross-population extended haplotype homozygosity (XP-EHH) and population differentiation (FST) to disentangle the genetic mechanisms involved in adaptation and phenotypic change by a rapid and major environmental transition. To tackle these questions, we combined SNP array data (~54,000 SNPs) in Creole breeds with their modern putative Iberian ancestors. Reconstruction of the population history of Creoles from the end of the 15th century indicated a major demographic expansion until the introduction of zebu and commercial breeds into the Americas ~180 years ago, coinciding with a drastic Ne contraction. NeS analysis provided insights into short-term complexity in population change and depicted a decrease/expansion episode at the end of the ABC-inferred expansion, as well as several additional fluctuations in Ne with the attainment of the current small Ne only towards the end of the 20th century. Selection signatures for tropical adaptation pinpointed the thermoregulatory slick hair coat region, identifying a new candidate gene (GDNF), as well as novel candidate regions involved in immune function, behavioural processes, iron metabolism and adaptation to new feeding conditions. The outcomes from this study will help in future-proofing farm animal genetic resources (FAnGR) by providing molecular tools that allow selection for improved cattle performance, resilience and welfare under climate change.}, } @article {pmid30622638, year = {2019}, author = {Vigueira, CC and Qi, X and Song, BK and Li, LF and Caicedo, AL and Jia, Y and Olsen, KM}, title = {Call of the wild rice: Oryza rufipogon shapes weedy rice evolution in Southeast Asia.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {93-104}, doi = {10.1111/eva.12581}, pmid = {30622638}, issn = {1752-4571}, abstract = {Agricultural weeds serve as productive models for studying the genetic basis of rapid adaptation, with weed-adaptive traits potentially evolving multiple times independently in geographically distinct but environmentally similar agroecosystems. Weedy relatives of domesticated crops can be especially interesting systems because of the potential for weed-adaptive alleles to originate through multiple mechanisms, including introgression from cultivated and/or wild relatives, standing genetic variation, and de novo mutations. Weedy rice populations have evolved multiple times through dedomestication from cultivated rice. Much of the genomic work to date in weedy rice has focused on populations that exist outside the range of the wild crop progenitor. In this study, we use genome-wide SNPs generated through genotyping-by-sequencing to compare the evolution of weedy rice in regions outside the range of wild rice (North America, South Korea) and populations in Southeast Asia, where wild rice populations are present. We find evidence for adaptive introgression of wild rice alleles into weedy rice populations in Southeast Asia, with the relative contributions of wild and cultivated rice alleles varying across the genome. In addition, gene regions underlying several weed-adaptive traits are dominated by genomic contributions from wild rice. Genome-wide nucleotide diversity is also much higher in Southeast Asian weeds than in North American and South Korean weeds. Besides reflecting introgression from wild rice, this difference in diversity likely reflects genetic contributions from diverse cultivated landraces that may have served as the progenitors of these weedy populations. These important differences in weedy rice evolution in regions with and without wild rice could inform region-specific management strategies for weed control.}, } @article {pmid30622637, year = {2019}, author = {Taitano, N and Bernau, V and Jardón-Barbolla, L and Leckie, B and Mazourek, M and Mercer, K and McHale, L and Michel, A and Baumler, D and Kantar, M and van der Knaap, E}, title = {Genome-wide genotyping of a novel Mexican Chile Pepper collection illuminates the history of landrace differentiation after Capsicum annuum L. domestication.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {78-92}, doi = {10.1111/eva.12651}, pmid = {30622637}, issn = {1752-4571}, abstract = {Studies of genetic diversity among phenotypically distinct crop landraces improve our understanding of fruit evolution and genome structure under domestication. Chile peppers (Capsicum spp. L.) are economically valuable and culturally important species, and extensive phenotypic variation among landraces exists in southern Mexico, a center of C. annuum diversity. We collected 103 chile pepper seed accessions from 22 named landraces across 27 locations in southern Mexico. We genotyped these accessions with genotyping by sequencing (GBS), yielding 32,623 filtered single-nucleotide polymorphisms. Afterward, we genotyped 32 additional C. annuum accessions from a global collection for comparison to the Mexican collection. Within the Mexican collection, genetic assignment analyses showed clear genetic differentiation between landraces and clarified the unique nature of the Tusta landrace. Further clustering analyses indicated that the largest fresh-use Chile de Agua and dry-use Costeño landraces were part of separate clades, indicating that these two landraces likely represent distinct populations. The global accessions showed considerable admixture and limited clustering, which may be due to the collapse of use-type divisions outside of Central America. The separation of the Mexican landraces in part by fruit morphology related to use highlights the relevance of this use-type morphological diversity for plant breeders and the utility of fruit development variation for evolutionary biologists.}, } @article {pmid30622636, year = {2019}, author = {Schreiber, M and Himmelbach, A and Börner, A and Mascher, M}, title = {Genetic diversity and relationship between domesticated rye and its wild relatives as revealed through genotyping-by-sequencing.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {66-77}, doi = {10.1111/eva.12624}, pmid = {30622636}, issn = {1752-4571}, abstract = {Rye (Secale cereale L.) is a cereal grass that is an important food crop in Central and Eastern Europe. In contrast to its close relatives wheat and barley, it was not a founder crop of Neolithic agriculture, but is considered a secondary domesticate that may have become a crop plant only after a transitory phase as a weed. As a minor crop of only local importance, genomic resources in rye are underdeveloped, and few population genetic studies using genomewide markers have been published to date. We collected genotyping-by-sequencing data for 603 individuals from 101 genebank accessions of domesticated rye and its wild progenitor S. cereale subsp. vavilovii and related species in the genus Secale. Variant detection in the context of a recently published draft sequence assembly of cultivated rye yielded 55,744 single nucleotide polymorphisms with present genotype calls in 90% of samples. Analysis of population structure recapitulated the taxonomy of the genus Secale. We found only weak genetic differentiation between wild and domesticated rye with likely gene flow between the two groups. Moreover, incomplete lineage sorting was frequent between Secale species because of either ongoing gene flow or recent speciation. Our study highlights the necessity of gauging the representativeness of ex situ germplasm collections for domestication studies and motivates a more in-depth analysis of the interplay between sequence divergence and reproductive isolation in the genus Secale.}, } @article {pmid30622635, year = {2019}, author = {Owens, GL and Baute, GJ and Hubner, S and Rieseberg, LH}, title = {Genomic sequence and copy number evolution during hybrid crop development in sunflowers.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {54-65}, doi = {10.1111/eva.12603}, pmid = {30622635}, issn = {1752-4571}, abstract = {Hybrid crops, an important part of modern agriculture, rely on the development of male and female heterotic gene pools. In sunflowers, heterotic gene pools were developed through the use of crop-wild relatives to produce cytoplasmic male sterile female and branching, fertility restoring male lines. Here, we use genomic data from a diversity panel of male, female, and open-pollinated lines to explore the genetic changes brought during modern improvement. We find the male lines have diverged most from their open-pollinated progenitors and that genetic differentiation is concentrated in chromosomes, 8, 10 and 13, due to introgressions from wild relatives. Ancestral variation from open-pollinated varieties almost universally evolved in parallel for both male and female lines suggesting little or no selection for heterotic overdominance. Furthermore, we show that gene content differs between the male and female lines and that differentiation in gene content is concentrated in high FST regions. This means that the introgressions that brought branching and fertility restoration to the male lines, brought with them different gene content from the ancestral haplotypes, including the removal of some genes. Although we find no evidence that gene complementation genomewide is responsible for heterosis between male and female lines, several of the genes that are largely absent in either the male or female lines are associated with pathogen defense, suggesting complementation may be functionally relevant for crop breeders.}, } @article {pmid30622634, year = {2019}, author = {Wales, N and Akman, M and Watson, RHB and Sánchez Barreiro, F and Smith, BD and Gremillion, KJ and Gilbert, MTP and Blackman, BK}, title = {Ancient DNA reveals the timing and persistence of organellar genetic bottlenecks over 3,000 years of sunflower domestication and improvement.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {38-53}, doi = {10.1111/eva.12594}, pmid = {30622634}, issn = {1752-4571}, abstract = {Here, we report a comprehensive paleogenomic study of archaeological and ethnographic sunflower remains that provides significant new insights into the process of domestication of this important crop. DNA from both ancient and historic contexts yielded high proportions of endogenous DNA, and although archaeological DNA was found to be highly degraded, it still provided sufficient coverage to analyze genetic changes over time. Shotgun sequencing data from specimens from the Eden's Bluff archaeological site in Arkansas yielded organellar DNA sequence from specimens up to 3,100 years old. Their sequences match those of modern cultivated sunflowers and are consistent with an early domestication bottleneck in this species. Our findings also suggest that recent breeding of sunflowers has led to a loss of genetic diversity that was present only a century ago in Native American landraces. These breeding episodes also left a profound signature on the mitochondrial and plastid haplotypes in cultivars, as two types were intentionally introduced from other Helianthus species for crop improvement. These findings gained from ancient and historic sunflower specimens underscore how future in-depth gene-based analyses can advance our understanding of the pace and targets of selection during the domestication of sunflower and other crop species.}, } @article {pmid30622633, year = {2019}, author = {Allaby, RG and Ware, RL and Kistler, L}, title = {A re-evaluation of the domestication bottleneck from archaeogenomic evidence.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {29-37}, doi = {10.1111/eva.12680}, pmid = {30622633}, issn = {1752-4571}, abstract = {Domesticated crops show a reduced level of diversity that is commonly attributed to the "domestication bottleneck"; a drastic reduction in the population size associated with subsampling the wild progenitor species and the imposition of selection pressures associated with the domestication syndrome. A prediction of the domestication bottleneck is a sharp decline in genetic diversity early in the domestication process. Surprisingly, archaeological genomes of three major annual crops do not indicate that such a drop in diversity occurred early in the domestication process. In light of this observation, we revisit the general assumption of the domestication bottleneck concept in our current understanding of the evolutionary process of domestication.}, } @article {pmid30622632, year = {2019}, author = {Plekhanova, E and Nuzhdin, SV and Utkin, LV and Samsonova, MG}, title = {Prediction of deleterious mutations in coding regions of mammals with transfer learning.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {18-28}, doi = {10.1111/eva.12607}, pmid = {30622632}, issn = {1752-4571}, abstract = {The genomes of mammals contain thousands of deleterious mutations. It is important to be able to recognize them with high precision. In conservation biology, the small size of fragmented populations results in accumulation of damaging variants. Preserving animals with less damaged genomes could optimize conservation efforts. In breeding of farm animals, trade-offs between farm performance versus general fitness might be better avoided if deleterious mutations are well classified. In humans, the problem of such a precise classification has been successfully solved, in large part due to large databases of disease-causing mutations. However, this kind of information is very limited for other mammals. Here, we propose to better use information available on human mutations to enable classification of damaging mutations in other mammalian species. Specifically, we apply transfer learning-machine learning methods-improving small dataset for solving a focal problem (recognizing damaging mutations in our companion and farm animals) due to the use of much large datasets available for solving a related problem (recognizing damaging mutations in humans). We validate our tools using mouse and dog annotated datasets and obtain significantly better results in companion to the SIFT classifier. Then, we apply them to predict deleterious mutations in cattle genomewide dataset.}, } @article {pmid30622631, year = {2019}, author = {Bosse, M and Megens, HJ and Derks, MFL and de Cara, ÁMR and Groenen, MAM}, title = {Deleterious alleles in the context of domestication, inbreeding, and selection.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {6-17}, doi = {10.1111/eva.12691}, pmid = {30622631}, issn = {1752-4571}, abstract = {Each individual has a certain number of harmful mutations in its genome. These mutations can lower the fitness of the individual carrying them, dependent on their dominance and selection coefficient. Effective population size, selection, and admixture are known to affect the occurrence of such mutations in a population. The relative roles of demography and selection are a key in understanding the process of adaptation. These are factors that are potentially influenced and confounded in domestic animals. Here, we hypothesize that the series of events of bottlenecks, introgression, and strong artificial selection associated with domestication increased mutational load in domestic species. Yet, mutational load is hard to quantify, so there are very few studies available revealing the relevance of evolutionary processes. The precise role of artificial selection, bottlenecks, and introgression in further increasing the load of deleterious variants in animals in breeding and conservation programmes remains unclear. In this paper, we review the effects of domestication and selection on mutational load in domestic species. Moreover, we test some hypotheses on higher mutational load due to domestication and selective sweeps using sequence data from commercial pig and chicken lines. Overall, we argue that domestication by itself is not a prerequisite for genetic erosion, indicating that fitness potential does not need to decline. Rather, mutational load in domestic species can be influenced by many factors, but consistent or strong trends are not yet clear. However, methods emerging from molecular genetics allow discrimination of hypotheses about the determinants of mutational load, such as effective population size, inbreeding, and selection, in domestic systems. These findings make us rethink the effect of our current breeding schemes on fitness of populations.}, } @article {pmid30622630, year = {2019}, author = {Kantar, MB and Bruford, MW and Rieseberg, LH}, title = {The genomics of domestication special issue editorial.}, journal = {Evolutionary applications}, volume = {12}, number = {1}, pages = {3-5}, doi = {10.1111/eva.12693}, pmid = {30622630}, issn = {1752-4571}, abstract = {Domestication has been of major interest to biologists for centuries, whether for creating new plants and animal types or more formally exploring the principles of evolution. Such studies have long used combinations of phenotypic and genetic evidence. Recently, the advent of a large number of genomes and genomic tools across a wide array of domesticated plant and animal species has reinvigorated the study of domestication. These genomic data, which can be easily generated for nearly any species, often provide great insight with or without a reference genome. The comparison of genome wide data from domestic and wild species has ignited a wave of insight into human, plant, and animal history with a new range of questions becoming accessible. With this in mind, this issue of Evolutionary Applications includes eleven papers covering a wide range of perspectives and methodologies relevant to understanding genomic variation under domestication.}, } @article {pmid30619603, year = {2018}, author = {Schenkel, MA and Pen, I and Beukeboom, LW and Billeter, JC}, title = {Making sense of intralocus and interlocus sexual conflict.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {13035-13050}, doi = {10.1002/ece3.4629}, pmid = {30619603}, issn = {2045-7758}, abstract = {Sexual conflict occurs because males and females are exposed to different selection pressures. This can affect many aspects of female and male biology, such as physiology, behavior, genetics, and even population ecology. Its broad impact has caused widespread interest in sexual conflict. However, a key aspect of sexual conflict is often confused; it comprises two distinct forms: intralocus and interlocus sexual conflict (IASC and IRSC). Although both are caused by sex differences in selection, they operate via different proximate and ultimate mechanisms. Intralocus sexual conflict and IRSC are often not clearly defined as separate processes in the scientific literature, which impedes a proper understanding of each form as well as of their relative impact on sexual conflict. Furthermore, our current knowledge of the genetics of these phenomena is severely limited. This prevents us from empirically testing numerous theories regarding the role of these two forms of sexual conflict in evolution. Here, we clarify the distinction between IASC and IRSC, by discussing how male and female interests differ, how and when sex-specific adaptation occurs, and how this may lead to evolutionary change. We then describe a framework for their study, focusing on how future experiments may help identify the genetics underlying these phenomena. Through this, we hope to promote a more critical reflection on IASC and IRSC as well as underline the necessity of genetic and mechanistic studies of these two phenomena.}, } @article {pmid30619602, year = {2018}, author = {Ottenburghs, J}, title = {Exploring the hybrid speciation continuum in birds.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {13027-13034}, doi = {10.1002/ece3.4558}, pmid = {30619602}, issn = {2045-7758}, abstract = {Hybridization is increasingly recognized as a creative evolutionary force contributing to adaptation and speciation. Homoploid hybrid speciation-the process in which hybridization results in a stable, fertile, and reproductively isolated hybrid lineage where there is no change in ploidy-has been documented in several taxa. Hybridization can directly contribute to reproductive isolation or reinforce it at a later stage. Alternatively, hybridization might not be related to the evolution of reproductive isolation. To account for these different scenarios, I propose to discriminate between two types of hybrid speciation: type I where reproductive isolation is a direct consequence of hybridization and type II where it is the by-product of other processes. I illustrate the applicability of this classification scheme with avian examples. To my knowledge, seven hybrid bird species have been proposed: Italian sparrow, Audubon's warbler, Genovesa mockingbird, Hawaiian duck, red-breasted goose, golden-crowned manakin, and a recent lineage of Darwin's finches on the island of Daphne Major ("Big Bird"). All studies provide convincing evidence for hybridization, but do not always confidently discriminate between scenarios of hybrid speciation and recurrent introgressive hybridization. The build-up of reproductive isolation between the hybrid species and their parental taxa is mainly driven by premating isolation mechanisms and comparable to classical speciation events. One hybrid species can be classified as type I ("Big Bird") while three species constitute type II hybrid species (Italian sparrow, Audubon's warbler, and golden-crowned manakin). The diversity in hybrid bird species across a range of divergence times also provides an excellent opportunity to study the evolution of hybrid genomes in terms of genome stabilization and adaptation.}, } @article {pmid30619601, year = {2018}, author = {Hou, Z and Wang, Z and Ye, Z and Du, S and Liu, S and Zhang, J}, title = {Phylogeographic analyses of a widely distributed Populus davidiana: Further evidence for the existence of glacial refugia of cool-temperate deciduous trees in northern East Asia.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {13014-13026}, doi = {10.1002/ece3.4755}, pmid = {30619601}, issn = {2045-7758}, abstract = {Despite several phylogeographic studies had provided evidence to support the existence of glacial refugia of cool-temperate deciduous trees in northeast China, the species used in these studies were limited by the species ranges, which could not exclude the possibility that northern populations were the colonists from southern refugial populations during the last glacial maximum (LGM). Here, we estimated the nucleotide variation in Populus davidiana, a widespread species distributed in Eurasia. Three groups in northeast, central, and southwest China were constructed according to the simulation results from SAMOVA, composition of chloroplast haplotypes and structure results. We revealed that the northeast China had endemic haplotypes, the haplotypes and nucleotide diversity in northern regions were not lower than that in southern China, and this species has not experienced population expansion base on the estimation of Bayesian skyline plots. Ecological niche modeling (ENM) indicated that the northeast China had a high suitability score during the last glacial maximum. The combined evidence clearly demonstrated that northeastern and southwestern refugia were maintained across the current distributional range of P. davidiana during the LGM. The genetic differentiation between these two refugia might be mainly caused by differences of climate among these areas. The phylogeographic analyses of a widely distributed P. davidiana provided robust evidence to clarify the issue of refugia in northeast China, and these results are of great importance for understanding the influence of Quaternary glaciations on the distribution and evolution of species in East Asia.}, } @article {pmid30619600, year = {2018}, author = {Li, S and Liu, D and Zhang, R and Zhai, Y and Huang, X and Wang, D and Shi, X}, title = {Effects of a presumably protective endosymbiont on life-history characters and their plasticity for its host aphid on three plants.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {13004-13013}, doi = {10.1002/ece3.4754}, pmid = {30619600}, issn = {2045-7758}, abstract = {Hamiltonella defensa is well known for its protective roles against parasitoids for its aphid hosts, but its functional roles in insect-plant interactions are less understood. Thus, the impact of H. defensa infections on life-history characters and the underlying genetic variation for the grain aphid, Sitobion avenae (Fabricius), was explored on three plants (i.e., wheat, oat, and rye). Compared to cured lines, H. defensa infected lines of S. avenae had lower fecundity on wheat and oat, but not on rye, suggesting an infection cost for the aphid on susceptible host plants. However, when tested on rye, the infected lines showed a shorter developmental time for the nymphal stage than corresponding cured lines, showing some benefit for S. avenae carrying the endosymbiont on resistant host plants. The infection of H. defensa altered genetic variation underlying its host S. avenea's life-history characters, which was shown by differences in heritabilities and genetic correlations of life-history characters between S. avenae lines infected and cured of the endosymbiont. This was further substantiated by disparity in G-matrices of their life-history characters for the two types of aphid lines. The G-matrices for life-history characters of aphid lines infected with and cured of H. defensa were significantly different from each other on rye, but not on oat, suggesting strong plant-dependent effects. The developmental durations of infected S. avenae lines showed a lower plasticity compared with those of corresponding cured lines, and this could mean higher adaptability for the infected lines.Overall, our results showed novel functional roles of a common secondary endosymbiont (i.e., H. defensa) in plant-insect interactions, and its infections could have significant consequences for the evolutionary ecology of its host insect populations in nature.}, } @article {pmid30619599, year = {2018}, author = {MacLaren, AR and Crump, PS and Royle, JA and Forstner, MRJ}, title = {Observer-free experimental evaluation of habitat and distance effects on the detection of anuran and bird vocalizations.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12991-13003}, doi = {10.1002/ece3.4752}, pmid = {30619599}, issn = {2045-7758}, abstract = {Acoustic surveys of vocalizing animals are conducted to determine density, distribution, and diversity. Acoustic surveys are traditionally performed by human listeners, but automated recording devices (ARD) are becoming increasingly popular. Signal strength decays, or attenuates, with increasing distance between source and receiver and some habitat types may differentially increase attenuation beyond the effects of distance alone. These combined effects are rarely accounted for in acoustic monitoring programs. We evaluated the performance of three playback devices and three ARD models using the calls of six anurans, six birds, and four pure tones. Based on these evaluations, we determined the optimal playback and recording devices. Using these optimal devices, we broadcast and recorded vocalizations in five habitat types along 1,000 m transects. We used generalized linear models to test for effects of habitat, distance, species, environmental, and landscape variables. We predicted detection probabilities for each vocalization, in each habitat type, from 0 to 1,000 m. Among playback devices, only a remote predator caller simulated vocalizations consistently. Differences of ~10 dB were observed among ARDs. For all species, we found differences in detectability between open and closed canopy habitats. We observed large differences in predicted detection probability among species in each habitat type, as well as along 1,000 m transects. Increases in temperature, barometric pressure, and wind speed significantly decreased detection probability. However, aside from differences among species, habitat, and distance, topography impeding a line-of-sight between sound source and receiver had the greatest negative influence on detections. Our results suggest researchers should model the effects of habitat, distance, and frequency on detection probability when performing acoustic surveys. To optimize survey design, we recommend pilot measurements among varying habitats.}, } @article {pmid30619598, year = {2018}, author = {Ida, TY and Takanashi, K and Tamura, M and Ozawa, R and Nakashima, Y and Ohgushi, T}, title = {Defensive chemicals of neighboring plants limit visits of herbivorous insects: Associational resistance within a plant population.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12981-12990}, doi = {10.1002/ece3.4750}, pmid = {30619598}, issn = {2045-7758}, abstract = {Despite our understanding of chemical defenses and their consequences for plant performance and herbivores, we know little about whether defensive chemicals in plant tissues, such as alkaloids, and their spatial variation within a population play unappreciated and critical roles in plant-herbivore interactions. Neighboring plants can decrease or increase attractiveness of a plant to herbivores, an example of a neighborhood effect. Chemical defensive traits may contribute to neighborhood effects in plant-herbivore interactions. We examined the effects of nicotine in leaves (a non-emitted defense chemical) on plant-herbivore interactions in a spatial context, using two varieties of Nicotiana tabacum with different nicotine levels. A common garden experiment demonstrated that visits by grasshoppers decreased with increasing density of neighboring plants with a greater nicotine level. In contrast, visits of leaf caterpillars were not affected by neighbors, irrespective of nicotine levels. Thus, our results clearly highlighted that the neighborhood effect caused by the nicotine in leaves depended on the insect identity, and it was mediated by plant-herbivore interactions, rather than plant-plant interactions. This study demonstrates that understanding of effects of plant defensive traits on plant-herbivore interactions requires careful consideration of the spatial distribution of plant defenses, and provides support for the importance of spatial context to accurately capture the ecological and evolutionary consequences of plant-herbivore interactions.}, } @article {pmid30619597, year = {2018}, author = {Schell, CJ and Young, JK and Lonsdorf, EV and Santymire, RM and Mateo, JM}, title = {Parental habituation to human disturbance over time reduces fear of humans in coyote offspring.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12965-12980}, doi = {10.1002/ece3.4741}, pmid = {30619597}, issn = {2045-7758}, abstract = {A fundamental tenet of maternal effects assumes that maternal variance over time should have discordant consequences for offspring traits across litters. Yet, seldom are parents observed across multiple reproductive bouts, with few studies considering anthropogenic disturbances as an ecological driver of maternal effects. We observed captive coyote (Canis latrans) pairs over two successive litters to determine whether among-litter differences in behavior (i.e., risk-taking) and hormones (i.e., cortisol and testosterone) corresponded with parental plasticity in habituation. Thus, we explicitly test the hypothesis that accumulating experiences of anthropogenic disturbance reduces parental fear across reproductive bouts, which should have disparate phenotypic consequences for first- and second-litter offspring. To quantify risk-taking behavior, we used foraging assays from 5-15 weeks of age with a human observer present as a proxy for human disturbance. At 5, 10, and 15 weeks of age, we collected shaved hair to quantify pup hormone levels. We then used a quantitative genetic approach to estimate heritability, repeatability, and between-trait correlations. We found that parents were riskier (i.e., foraged more frequently) with their second versus first litters, supporting our prediction that parents become increasingly habituated over time. Second-litter pups were also less risk-averse than their first-litter siblings. Heritability for all traits did not differ from zero (0.001-0.018); however, we found moderate support for repeatability in all observed traits (r = 0.085-0.421). Lastly, we found evidence of positive phenotypic and cohort correlations among pup traits, implying that cohort identity (i.e., common environment) contributes to the development of phenotypic syndromes in coyote pups. Our results suggest that parental habituation may be an ecological cue for offspring to reduce their fear response, thus emphasizing the role of parental plasticity in shaping their pups' behavioral and hormonal responses toward humans.}, } @article {pmid30619596, year = {2018}, author = {Fronhofer, EA and Liebig, J and Mitesser, O and Poethke, HJ}, title = {Eusociality outcompetes egalitarian and solitary strategies when resources are limited and reproduction is costly.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12953-12964}, doi = {10.1002/ece3.4737}, pmid = {30619596}, issn = {2045-7758}, abstract = {Explaining the evolution and maintenance of animal groups remains a challenge. Surprisingly, fundamental ecological factors, such as resource variance and competition for limited resources, tend to be ignored in models of cooperation. We use a mathematical model previously developed to quantify the influence of different group sizes on resource use efficiency in egalitarian groups and extend its scope to groups with severe reproductive skew (eusocial groups). Accounting for resource limitation, the model allows calculation of optimal group sizes (highest resource use efficiency) and equilibrium population sizes in egalitarian as well as eusocial groups for a broad spectrum of environmental conditions (variance of resource supply). We show that, in contrast to egalitarian groups, eusocial groups may not only reduce variance in resource supply for survival, thus reducing the risk of starvation, they may also increase variance in resource supply for reproduction. The latter effect allows reproduction even in situations when resources are scarce. These two facets of eusocial groups, resource sharing for survival and resource pooling for reproduction, constitute two beneficial mechanisms of group formation. In a majority of environmental situations, these two benefits of eusociality increase resource use efficiency and lead to supersaturation-a strong increase in carrying capacity. The increase in resource use efficiency provides indirect benefits to group members even for low intra-group relatedness and may represent one potential explanation for the evolution and especially the maintenance of eusociality and cooperative breeding.}, } @article {pmid30619595, year = {2018}, author = {Baecher, JA and Richter, SC}, title = {Environmental gradients in old-growth Appalachian forest predict fine-scale distribution, co-occurrence, and density of woodland salamanders.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12940-12952}, doi = {10.1002/ece3.4736}, pmid = {30619595}, issn = {2045-7758}, abstract = {Woodland salamanders are among the most abundant vertebrate animals in temperate deciduous forests of eastern North America. Because of their abundance, woodland salamanders are responsible for the transformation of nutrients and translocation of energy between highly disparate levels of trophic organization: detrital food webs and high-order predators. However, the spatial extent of woodland salamanders' role in the ecosystem is likely contingent upon the distribution of their biomass throughout the forest. We sought to determine if natural environmental gradients influence the fine-scale distribution and density of Southern Ravine Salamanders (Plethodon richmondi) and Cumberland Plateau Salamanders (P. kentucki). We addressed this objective by constructing occupancy, co-occurrence, and abundance models from temporally replicated surveys within an old-growth forest in the Cumberland Plateau region of Kentucky. We found that Plethodon richmondi had a more restricted fine-scale distribution than P. kentucki (mean occupancy probability [ ψ ¯ ^ ] = 0.737) and exhibited variable density, from <250 to >1000 individuals per hectare, associated with increased soil moisture and reduced solar exposure due to slope face. While more ubiquitously distributed (ψ ¯ ^ = 0.95), P. kentucki density varied from <400 to >1,000 individuals per hectare and was inversely related to increased solar exposure from canopy disturbance and landscape convexity. Our data suggest co-occurrence patterns of P. richmondi and P. kentucki are influenced primarily by abiotic conditions within the forest, and that populations likely occur independently and without evidence of biotic interaction. Given the critical role that woodland salamanders play in the maintenance of forest health, regions that support large populations of woodland salamanders, such as those highlighted in this study-mesic forest stands on north-to-east facing slopes with dense canopy and abundant natural cover, may provide enhanced ecosystem services and support the stability of the total forest.}, } @article {pmid30619594, year = {2018}, author = {Sherratt, E and Anstis, M and Keogh, JS}, title = {Ecomorphological diversity of Australian tadpoles.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12929-12939}, doi = {10.1002/ece3.4733}, pmid = {30619594}, issn = {2045-7758}, abstract = {Ecomorphology is the association between an organism's morphology and its ecology. Larval anuran amphibians (tadpoles) are classified into distinct ecomorphological guilds based upon morphological features and observations of their ecology. The extent to which guilds comprise distinct morphologies resulting from convergent evolution, the degree of morphological variability within each guild, and the degree of continuity in shape between guilds has not previously been examined in a phylogenetically informed statistical framework. Here, we examine tadpole ecomorphological guilds at a macroevolutionary scale by examining morphological diversity across the Australian continent. We use ecological data to classify species to guilds, and geometric morphometrics to quantify body shape in the tadpoles of 188 species, 77% of Australian frog diversity. We find that the ecomorphological guilds represented by Australian species are morphologically distinct, but there is substantial morphological variation associated with each guild, and all guilds together form a morphological continuum. However, in a phylogenetic comparative context, there is no significant difference in body shape among guilds. We also relate the morphological diversity of the Australian assemblage of tadpoles to a global sample and demonstrate that ecomorphological diversity of Australian tadpoles is limited with respect to worldwide species. Our results demonstrate that general patterns of ecomorphological variation are upheld in Australian tadpoles, but tadpole body shape is more variable and possibly generalist than generally appreciated.}, } @article {pmid30619593, year = {2018}, author = {Sambhu, H and Nankishore, A and Turton, SM and Northfield, TD}, title = {Trade-offs for butterfly alpha and beta diversity in human-modified landscapes and tropical rainforests.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12918-12928}, doi = {10.1002/ece3.4732}, pmid = {30619593}, issn = {2045-7758}, abstract = {The accelerating expansion of human populations and associated economic activity across the globe have made maintaining large, intact natural areas increasingly challenging. The difficulty of preserving large intact landscapes in the presence of growing human populations has led to a growing emphasis on landscape approaches to biodiversity conservation with a complementary strategy focused on improving conservation in human-modified landscapes. This, in turn, is leading to intense debate about the effectiveness of biodiversity conservation in human-modified landscapes and approaches to better support biodiversity in those landscapes. Here, we compared butterfly abundance, alpha richness, and beta diversity in human-modified landscapes (urban, sugarcane) and natural, forested areas to assess the conservation value of human-modified landscapes within the Wet Tropics bioregion of Australia. We used fruit-baited traps to sample butterflies and analyzed abundance and species richness in respective land uses over a one-year period. We also evaluated turnover and spatial variance components of beta diversity to determine the extent of change in temporal and spatial variation in community composition. Forests supported the largest numbers of butterflies, but were lowest in each, alpha species richness, beta turnover, and the spatial beta diversity. Sugarcane supported higher species richness, demonstrating the potential for conservation at local scales in human-modified landscapes. In contrast, beta diversity was highest in urban areas, likely driven by spatial and temporal variation in plant composition within the urban landscapes. Thus, while improving conservation on human-modified landscapes may improve local alpha richness, conserving variation in natural vegetation is critical for maintaining high beta diversity.}, } @article {pmid30619592, year = {2018}, author = {Cutting, KA and Ferguson, JM and Anderson, ML and Cook, K and Davis, SC and Levine, R}, title = {Linking beaver dam affected flow dynamics to upstream passage of Arctic grayling.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12905-12917}, doi = {10.1002/ece3.4728}, pmid = {30619592}, issn = {2045-7758}, abstract = {Beaver reintroductions and beaver dam structures are an increasingly utilized ecological tool for rehabilitating degraded streams, yet beaver dams can potentially impact upstream fish migrations. We collected two years of data on Arctic grayling movement through a series of beaver dams in a low gradient mountain stream, utilizing radio-telemetry techniques, to determine how hydrology, dam characteristics, and fish attributes impeded passage and movement rates of spawning grayling. We compared fish movement between a "normal" flow year and a "low" flow year, determined grayling passage probabilities over dams in relation to a suite of factors, and predicted daily movement rates in relation to the number of dams each fish passed and distance between dams during upstream migration to spawning areas. We found that the average passage probability over unbreached beaver dams was 88%, though we found that it fell below 50% at specific dams. Upstream passage of grayling was affected by three main characteristics: (a) temperature, (b) breach status, and (c) hydrologic linkages that connect sections of stream above and below the dam. Other variables influence passage, but to a lesser degree. Cumulative passage varied with distance upstream and total number of dams passed in low versus normal flow years, while movement rates upstream slowed as fish swam closer to dams. Our findings demonstrate that upstream passage of fish over beaver dams is strongly correlated with hydrologic conditions with moderate controls by dam- and fish-level characteristics. Our results provide a framework that can be applied to reduce barrier effects when and where beaver dams pose a significant threat to the upstream migration of fish populations while maintaining the diverse ecological benefits of beaver activity when dams are not a threat to fish passage.}, } @article {pmid30619591, year = {2018}, author = {Balmer, B and Zolman, E and Rowles, T and Smith, C and Townsend, F and Fauquier, D and George, C and Goldstein, T and Hansen, L and Quigley, B and McFee, W and Morey, J and Rosel, P and Saliki, J and Speakman, T and Schwacke, L}, title = {Ranging patterns, spatial overlap, and association with dolphin morbillivirus exposure in common bottlenose dolphins (Tursiops truncatus) along the Georgia, USA coast.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12890-12904}, doi = {10.1002/ece3.4727}, pmid = {30619591}, issn = {2045-7758}, abstract = {During 2013-2015, an outbreak of dolphin morbillivirus (DMV) occurred in the western North Atlantic, which resulted in the stranding of over 1,600 common bottlenose dolphins (Tursiops truncatus). There are currently five coastal and 10 bay, sound, and estuary dolphin stocks along the U.S. Atlantic coast, yet there is very limited understanding of which stocks were exposed to DMV during the recent outbreak, or how DMV was transmitted across stocks. In order to address these questions, information is needed on spatial overlap and stock interactions. The goals of this project were to determine ranging patterns, prevalence of DMV, and spatial overlap of the South Carolina-Georgia (SC-GA) Coastal Stock, and adjacent Southern Georgia Estuarine System (SGES) Stock. During September 2015, a health assessment and telemetry study was conducted in which 19 dolphins were captured, tested for antibodies to DMV, and satellite tagged. Dolphins were classified into one of three ranging patterns (Coastal, Sound, or Estuary) based upon telemetry data. Coastal dolphins (likely members of the SC-GA Coastal Stock) had a significantly higher prevalence of positive DMV antibody titers (0.67; N = 2/3), than Sound and Estuary dolphins (likely members of the SGES Stock) (0.13; N = 2/16). These results suggest that the SC-GA Coastal Stock may have experienced greater exposure to DMV as compared to the SGES Stock. However, due to the small size of the SGES Stock and its exposure to high levels of persistent contaminants, this stock may be particularly vulnerable to DMV infection in the future.}, } @article {pmid30619590, year = {2018}, author = {Scherber, C and Andert, H and Niedringhaus, R and Tscharntke, T}, title = {A barrier island perspective on species-area relationships.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12879-12889}, doi = {10.1002/ece3.4726}, pmid = {30619590}, issn = {2045-7758}, abstract = {Predictions of species richness by island area are a classical cornerstone in ecology, while the specific features of barrier islands have been little appreciated. Many shorelines are occupied by barrier islands, which are shaped by offshore sedimentation processes and annual storm tide events. Hence, the appearance of these islands may vary between years if they are not protected by dykes. Here, we analyzed more than 2,990 species across 36 taxonomic groups (including vertebrates, invertebrates, and land plants) on German barrier islands, the East Frisian Islands. We tested for relationships between species richness or species incidence and island area (SAR), island habitat diversity and further island parameters using a range of generalized linear and mixed-effects models. Overall species richness was explained best by habitat diversity (Shannon index of habitat types). Analyses on the occurrence probability of individual species showed that changes of barrier island area by sedimentation and erosion, that is, barrier island-specific dynamics, explained the occurrence of 17 of 34 taxa, including most beetles, plants, and birds. Only six taxa such as spiders (249 species) and mammals (27 species) were primarily related to area. The diversity of habitat types was a key predictor for the incidence of twenty-five taxa, including ground beetles, true bugs and grasshoppers, amphibians, and reptiles. Overall, richness and incidence of taxa differed greatly in their responses, with area (although varying from 0.1 to 38.9 km2) playing a minor and island heterogeneity a major role, while barrier island-specific sedimentation and erosion turned out to additionally explain species richness and occurrence.}, } @article {pmid30619589, year = {2018}, author = {Curry, CM and Ross, JD and Contina, AJ and Bridge, ES}, title = {Varying dataset resolution alters predictive accuracy of spatially explicit ensemble models for avian species distribution.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12867-12878}, doi = {10.1002/ece3.4725}, pmid = {30619589}, issn = {2045-7758}, abstract = {Species distribution models can be made more accurate by use of new "Spatiotemporal Exploratory Models" (STEMs), a type of spatially explicit ensemble model (SEEM) developed at the continental scale that averages regional models pixel by pixel. Although SEEMs can generate more accurate predictions of species distributions, they are computationally expensive. We compared the accuracies of each model for 11 grassland bird species and examined whether they improve accuracy at a statewide scale for fine and coarse predictor resolutions. We used a combination of survey data and citizen science data for 11 grassland bird species in Oklahoma to test a spatially explicit ensemble model at a smaller scale for its effects on accuracy of current models. We found that only four species performed best with either a statewide model or SEEM; the most accurate model for the remaining seven species varied with data resolution and performance measure. Policy implications: Determination of nonheterogeneity may depend on the spatial resolution of the examined dataset. Managers should be cautious if any regional differences are expected when developing policy from range-wide results that show a single model or timeframe. We recommend use of standard species distribution models or other types of nonspatially explicit ensemble models for local species prediction models. Further study is necessary to understand at what point SEEMs become necessary with varying dataset resolutions.}, } @article {pmid30619588, year = {2018}, author = {Balfour, VL and Aumont, C and Dougherty, LR and Shuker, DM}, title = {The fitness effects of a pale mutant in the aposematic seed bug Lygaeus simulans indicate pleiotropy between warning coloration and life history.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12855-12866}, doi = {10.1002/ece3.4723}, pmid = {30619588}, issn = {2045-7758}, abstract = {Conspicuous warning colors that signal chemical or other defenses are common in the natural world. For instance, such aposematic warning patterns of red-and-black or yellow-and-black are common among insect taxa, particularly in the order Hemiptera, often forming the basis of Batesian and/or Müllerian mimicry rings. In addition, it has been repeatedly noted that color polymorphisms or mutants that influence pigmentation can show pleiotropy with other behavioral, physiological, or life-history traits. Here, we describe a pale mutant of the seed bug Lygaeus simulans that appeared in our laboratory population in 2012, which differs in color to the wild-type bugs. Through multigenerational experimental crosses between wild-type and pale mutant L. simulans, we first show that the pale phenotype segregates as a single Mendelian locus, with the pale allele being recessive to the wild type. Next, we show (a) that there is a large heterozygous advantage in terms of fecundity, (b) that pale females suffer reduced longevity, and (c) that pale males have increased body length compared to wild-type homozygotes. Our data therefore suggest that the color locus is pleiotropic with a number of life-history traits, opening the door for a more complete genetic analysis of aposematic coloration in this species. In addition, this phenotype will be useful as a visible genetic marker, providing a tool for investigating sperm competition and other post-copulatory drivers of sexual selection in this species.}, } @article {pmid30619587, year = {2018}, author = {Andriollo, T and Ashrafi, S and Arlettaz, R and Ruedi, M}, title = {Porous barriers? Assessment of gene flow within and among sympatric long-eared bat species.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12841-12854}, doi = {10.1002/ece3.4714}, pmid = {30619587}, issn = {2045-7758}, abstract = {Species are the basic units for measuring biodiversity and for comprehending biological interactions. Yet, their delineation is often contentious, especially in groups that are both diverse and phenotypically conservative. Three cryptic species of long-eared bats, Plecotus auritus, P. austriacus, and P. macrobullaris, co-occur over extensive areas of Western Europe. The latter is a fairly recent discovery, questioning the overall diversity of the entire Plecotus complex. Yet, high morphological and acoustic similarities compromise the reliable identification of long-eared bats in the field. We postulate that such extensive phenotypic overlap, along with the recurrent observation of morphologically intermediate individuals, may hide rampant interspecific hybridization. Based on a geographic sampling centered on areas of sympatry in the Alps and Corsica, we assessed the level of reproductive isolation of these three Plecotus species with mitochondrial and nuclear markers, looking at both inter- and intraspecific genetic population structuring. No sign of hybridization was detected between these three species that appear well separated biologically. Genetic structuring of populations, however, reflected different species-specific responses to environmental connectivity, that is, to the presence of orographic or sea barriers. While the Alpine range and the Ligurian Sea coincided with sharp genetic discontinuities in P. macrobullaris and P. austriacus, the more ubiquitous P. auritus showed no significant population structuration. There were clear phylogeographic discrepancies between microsatellite and mitochondrial markers at the intraspecific level, however, which challenges the reliance on simple barcoding approaches for the delineation of sound conservation units.}, } @article {pmid30619586, year = {2018}, author = {Benowitz, KM and Sparks, ME and McKinney, EC and Moore, PJ and Moore, AJ}, title = {Variation in mandible development and its relationship to dependence on parents across burying beetles.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12832-12840}, doi = {10.1002/ece3.4713}, pmid = {30619586}, issn = {2045-7758}, abstract = {Background: In species with parental care, there is striking variation in offspring dependence at birth, ranging from feeding independence to complete dependency on parents for nutrition. Frequently, highly dependent offspring further evolve reductions or alterations of morphological traits that would otherwise promote self-sufficiency. Here, we examine evidence for morphological evolution associated with dependence in burying beetles (Nicrophorus spp.), in which dependence upon parents appears to have several independent origins. In many species, precocial first instar larvae can survive without parenting, but several altricial species die at this stage on their own. We focused specifically on the mandibles, which are expected to be related to feeding ability and therefore independence from parents.

Results: We find no evidence that the size of the mandible is related to dependence on parents. However, we do find a developmental and phylogenetic correlation between independence and the presence of serrations on the inner edge of the mandible. Mandibles of independent species bear serrations at hatching, whereas dependent species hatch with smooth mandibles, only developing serrations in the second instar when these larvae gain the ability to survive on their own. Phylogenetic evidence suggests that serrations coincide with independence repeatedly. We note a single exception to this trend, a beetle with a serrated mandible that cannot survive without parents. However, this exception occurs in a species that has recently evolved the loss of independence.

Conclusions: We argue that the absence of mandible serrations occurs due to alternative selection pressures incurred in larvae dependent upon parents to survive. We suggest that this may have led to a variable function for mandibles, perhaps related to increased competitive ability among siblings or increased efficiency in receiving nutrition from parents. Furthermore, we propose that the phylogenetic pattern we see is consistent with the long-held evolutionary hypothesis that evolutionary change in behavior and physiology precede morphological change.}, } @article {pmid30619585, year = {2018}, author = {Stiffler, LL and Schroeder, KM and Anderson, JT and McRae, SB and Katzner, TE}, title = {Quantitative acoustic differentiation of cryptic species illustrated with King and Clapper rails.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12821-12831}, doi = {10.1002/ece3.4711}, pmid = {30619585}, issn = {2045-7758}, abstract = {Reliable species identification is vital for survey and monitoring programs. Recently, the development of digital technology for recording and analyzing vocalizations has assisted in acoustic surveying for cryptic, rare, or elusive species. However, the quantitative tools that exist for species differentiation are still being refined. Using vocalizations recorded in the course of ecological studies of a King Rail (Rallus elegans) and a Clapper Rail (Rallus crepitans) population, we assessed the accuracy and effectiveness of three parametric (logistic regression, discriminant function analysis, quadratic discriminant function analysis) and six nonparametric (support vector machine, CART, Random Forest, k-nearest neighbor, weighted k-nearest neighbor, and neural networks) statistical classification methods for differentiating these species by their kek mating call. We identified 480 kek notes of each species and quantitatively characterized them with five standardized acoustic parameters. Overall, nonparametric classification methods outperformed parametric classification methods for species differentiation (nonparametric tools were between 57% and 81% accurate, parametric tools were between 57% and 60% accurate). Of the nine classification methods, Random Forest was the most accurate and precise, resulting in 81.1% correct classification of kek notes to species. This suggests that the mating calls of these sister species are likely difficult for human observers to tell apart. However, it also implies that appropriate statistical tools may allow reasonable species-level classification accuracy of recorded calls and provide an alternative to species classification where other capture- or genotype-based survey techniques are not possible.}, } @article {pmid30619584, year = {2018}, author = {Riesle-Sbarbaro, SA and Amponsah-Mensah, K and de Vries, S and Nicolas, V and Lalis, A and Suu-Ire, R and Cunningham, AA and Wood, JLN and Sargan, DR}, title = {The Gambian epauletted fruit bat shows increased genetic divergence in the Ethiopian highlands and in an area of rapid urbanization.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12803-12820}, doi = {10.1002/ece3.4709}, pmid = {30619584}, issn = {2045-7758}, abstract = {The Gambian epauletted fruit bat (Epomophorus gambianus) is an abundant species that roosts in both urban and rural settings. The possible role of E. gambianus as a reservoir host of zoonotic diseases underlines the need to better understand the species movement patterns. So far, neither observational nor phylogenetic studies have identified the dispersal range or behavior of this species. Comparative analyses of mitochondrial and nuclear markers from 20 localities across the known distribution of E. gambianus showed population panmixia, except for the populations in Ethiopia and southern Ghana (Accra and Ve-Golokwati). The Ethiopian population may be ancestral and is highly divergent to the species across the rest of its range, possibly reflecting isolation of an ancient colonization along an east-west axis. Mitochondrial haplotypes in the Accra population display a strong signature of a past bottleneck event; evidence of either an ancient or recent bottleneck using microsatellite data, however, was not detected. Demographic analyses identified population expansion in most of the colonies, except in the female line of descent in the Accra population. The molecular analyses of the colonies from Ethiopia and southern Ghana show gender dispersal bias, with the mitochondrial DNA fixation values over ten times those of the nuclear markers. These findings indicate free mixing of the species across great distances, which should inform future epidemiological studies.}, } @article {pmid30619583, year = {2018}, author = {Chambault, P and de Thoisy, B and Huguin, M and Martin, J and Bonola, M and Etienne, D and Gresser, J and Hiélard, G and Mailles, J and Védie, F and Barnerias, C and Sutter, E and Guillemot, B and Dumont-Dayot, É and Régis, S and Lecerf, N and Lefebvre, F and Frouin, C and Aubert, N and Guimera, C and Bordes, R and Thieulle, L and Duru, M and Bouaziz, M and Pinson, A and Flora, F and Queneherve, P and Woignier, T and Allenou, JP and Cimiterra, N and Benhalilou, A and Murgale, C and Maillet, T and Rangon, L and Chanteux, N and Chanteur, B and Béranger, C and Le Maho, Y and Petit, O and Chevallier, D}, title = {Connecting paths between juvenile and adult habitats in the Atlantic green turtle using genetics and satellite tracking.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12790-12802}, doi = {10.1002/ece3.4708}, pmid = {30619583}, issn = {2045-7758}, abstract = {Although it is commonly assumed that female sea turtles always return to the beach they hatched, the pathways they use during the years preceding their first reproduction and their natal origins are most often unknown, as it is the case for juvenile green turtles found in Martinique waters in the Caribbean. Given the oceanic circulation of the Guiana current flowing toward Martinique and the presence of important nesting sites for this species in Suriname and French Guiana, we may assume that a large proportion of the juvenile green turtles found in Martinique are originating from the Suriname-French Guiana beaches. To confirm this hypothesis, we performed mixed stock analysis (MSA) on 40 green turtles sampled in Martinique Island and satellite tracked 31 juvenile green turtles tagged in Martinique to (a) assess their natal origin and (b) identify their destination. Our results from MSA confirm that these juveniles are descendant from females laying on several Caribbean and Atlantic beaches, mostly from Suriname and French Guiana, but also from more southern Brazilian beaches. These results were confirmed by the tracking data as the 10 turtles leaving Martinique headed across the Caribbean-Atlantic region in six different directions and 50% of these turtles reached the Brazilian foraging grounds used by the adult green turtles coming from French Guiana. One turtle left the French Guianan coast to perform the first transatlantic migration ever recorded in juvenile green turtles, swimming toward Guinea-Bissau, which is the most important nesting site for green turtles along the African coast. The extensive movements of the migrant turtles evidenced the crossing of international waters and more than 25 exclusive economic zones, reinforcing the need for an international cooperative network to ensure the conservation of future breeders in this endangered species.}, } @article {pmid30619582, year = {2018}, author = {Foucault, Q and Wieser, A and Waldvogel, AM and Feldmeyer, B and Pfenninger, M}, title = {Rapid adaptation to high temperatures in Chironomus riparius.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12780-12789}, doi = {10.1002/ece3.4706}, pmid = {30619582}, issn = {2045-7758}, abstract = {Effects of seasonal or daily temperature variation on fitness and physiology of ectothermic organisms and their ways to cope with such variations have been widely studied. However, the way multivoltines organisms cope with temperature variations from one generation to the next is still not well understood. The aim of this study was to investigate whether the multivoltine midge Chironomus riparius Meigen (1803) responds mainly via acclimation as predicted by current theories or whether rapid genetic adaptation is involved. To investigate this issue, a common garden approach has been applied. A mix of larvae from five European populations was raised in the laboratory at three different pre-exposure temperatures (PET): 14, 20, and 26°C. After three and five generations, respectively, larvae were exposed to three treatment temperatures (TT): 14, 20, and 26°C. Mortality was monitored for the first 48 hr and after emergence. After three generations, significant mortality rate differences depended on an interaction of PET and TT. This finding supports the hypothesis that chironomids respond rapidly to climatic variation via adaptive mechanisms and to a lesser extent via phenotypic plasticity. The result of the experiment indicates that three generations were sufficient to adapt to warm temperature, decreasing the mortality rate, highlighting the potential for chironomids to rapidly respond to seasonally changing conditions.}, } @article {pmid30619581, year = {2018}, author = {Fu, HP and Yuan, S and Man, DH and Chai, XX and Yang, SW and Bao, DH and Wu, XD}, title = {The burrow behavior and influenced factors of a prairie subterranean zokor (Myospalax psilurus).}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12773-12779}, doi = {10.1002/ece3.4705}, pmid = {30619581}, issn = {2045-7758}, abstract = {The Transbaikal zokor (Myospalax psilurus) is a dominant rodent distributed in the meadow steppe of Inner Mongolia in northern China. Due to long history of evolution in subterranean environment, the zokor has an adaptive behavior: sealing burrow entrances. When a burrow is damaged, exposed entrances appear, and within a relatively short time, the zokor would be active in sealing the entrances to reduce risks to its survival. In general, it is thought that zokors avoid light and wind, which is consistent with their behavior of sealing burrow entrances. However, direct evidence from field experimental research has been lacking. This study set up 68 field sampling points in a meadow steppe in Inner Mongolia from August to September, 2014 and used a wind-light isolator to study the effects of wind and light factors on zokor burrow entrance sealing behavior. The results showed that there were no significant correlations between wind or light factors and the frequency of zokor burrow entrance sealing. Therefore, wind and light factors are not direct factors associated with zokors actively sealing burrow entrances.}, } @article {pmid30619580, year = {2018}, author = {Maicher, V and Sáfián, S and Murkwe, M and Przybyłowicz, Ł and Janeček, Š and Fokam, EB and Pyrcz, T and Tropek, R}, title = {Flying between raindrops: Strong seasonal turnover of several Lepidoptera groups in lowland rainforests of Mount Cameroon.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12761-12772}, doi = {10.1002/ece3.4704}, pmid = {30619580}, issn = {2045-7758}, abstract = {Although seasonality in the tropics is often less pronounced than in temperate areas, tropical ecosystems show seasonal dynamics as well. Nevertheless, individual tropical insects' phenological patterns are still poorly understood, especially in the Afrotropics. To fill this gap, we investigated biodiversity patterns of Lepidoptera communities at three rainforest localities in the foothills of Mount Cameroon, West Africa, one of the wettest places in the world. Our multitaxa approach covered six lepidopteran groups (fruit-feeding butterflies and moths, the families Sphingidae, Saturniidae, and Eupterotidae, and the subfamily Arctiinae of Erebidae) with diverse life strategies. We sampled adults of the focal groups in three distinct seasons. Our sampling included standardized bait trapping (80 traps exposed for 10 days per locality and season) and attraction by light (six full nights per locality and season). Altogether, our dataset comprised 20,576 specimens belonging to 559 (morpho)species of the focal groups. The biodiversity of Lepidoptera generally increased in the high-dry season, and either increased (fruit-feeding moths, Arctiinae, Saturniidae) or decreased (butterflies, Sphingidae) in the transition to the wet season in particular groups. Simultaneously, we revealed a strong species turnover of fruit-feeding Lepidoptera and Arctiinae among the seasons, indicating relatively high specialization of these communities for particular seasons. Such temporal specialization can make the local communities of butterflies and moths especially sensitive to the expected seasonal perturbations caused by the global change. Because of the key role of Lepidoptera across trophic levels, such changes in their communities could strengthen this impact on entire tropical ecosystems.}, } @article {pmid30619579, year = {2018}, author = {Yuan, DY and Meng, X and Duan, CQ and Wei, ZH and Gao, W and Chang, JJ and Lv, XJ and Pan, Y}, title = {Effects of water exchange rate on morphological and physiological characteristics of two submerged macrophytes from Erhai Lake.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12750-12760}, doi = {10.1002/ece3.4703}, pmid = {30619579}, issn = {2045-7758}, abstract = {Growth patterns of aquatic macrophytes have been shown to vary in response to hydrological properties; however, such properties are typically characterized by water level fluctuation, flow velocity, flooding season, and sedimentation, but not by water exchange rate (WER). Herein, we experimentally investigated how WER (three levels: exchange 0%, 20%, and 40% of total water per day) affects water and sediment properties, and the consequences that these variations have on the individual responses of two submerged macrophytes, Hydrilla verticillata and Myriophyllum aquaticum which were planted in two different sediment types (sand and clay). In the experiment without ramets, it was found that turbidity, pH value, and dissolved carbon dioxide concentration of the system water were statistically unaffected by WER, while water dissolved oxygen (DO) concentration and sediment oxidation-reduction potential (ORP, in both sediments) consistently increased with increasing WER, regardless of experimental time. In the experiment containing ramets, biomass accumulation and relative growth rate (RGR) of both species gradually increased with increasing WER regardless of sediment type. The mechanisms were related to (a) increased oxygen availability, as indicated by gradually increased water DO concentration and sediment ORP; and (b) enhanced phosphorus (P) and nitrogen (N) absorbing abilities associated with stimulated root growth, reflected in increased mean root length, specific root length, and the root/above-ground biomass ratio, with increasing WER. Additionally, in the experiments containing ramets, significant linear relationships were consistently detected between sediment ORP and root parameters, root parameters and plant nutrients (N and P), and plant nutrients and plant growth conditions (biomass accumulation and RGR). These results demonstrate that WER plays an important role in determining oxygen availability and thus impacts the growth of submerged macrophytes by altering the ability of roots to absorb nutrients, indicating that ecosystem functions are more sensitive to WER than previously recognized.}, } @article {pmid30619578, year = {2018}, author = {Sohlström, EH and Marian, L and Barnes, AD and Haneda, NF and Scheu, S and Rall, BC and Brose, U and Jochum, M}, title = {Applying generalized allometric regressions to predict live body mass of tropical and temperate arthropods.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12737-12749}, doi = {10.1002/ece3.4702}, pmid = {30619578}, issn = {2045-7758}, abstract = {The ecological implications of body size extend from the biology of individual organisms to ecosystem-level processes. Measuring body mass for high numbers of invertebrates can be logistically challenging, making length-mass regressions useful for predicting body mass with minimal effort. However, standardized sets of scaling relationships covering a large range in body length, taxonomic groups, and multiple geographical regions are scarce. We collected 6,212 arthropods from 19 higher-level taxa in both temperate and tropical locations to compile a comprehensive set of linear models relating live body mass to a range of predictor variables. We measured live weight (hereafter, body mass), body length and width of each individual and conducted linear regressions to predict body mass using body length, body width, taxonomic group, and geographic region. Additionally, we quantified prediction discrepancy when using parameters from arthropods of a different geographic region. Incorporating body width into taxon- and region-specific length-mass regressions yielded the highest prediction accuracy for body mass. Using regression parameters from a different geographic region increased prediction discrepancy, causing over- or underestimation of body mass depending on geographical origin and whether body width was included. We present a comprehensive range of parameters for predicting arthropod body mass and provide guidance for selecting optimal scaling relationships. Given the importance of body mass for functional invertebrate ecology and the paucity of adequate regressions to predict arthropod body mass from different geographical regions, our study provides a long-needed resource for quantifying live body mass in invertebrate ecology research.}, } @article {pmid30619577, year = {2018}, author = {Radersma, R and Hegg, A and Noble, DWA and Uller, T}, title = {Timing of maternal exposure to toxic cyanobacteria and offspring fitness in Daphnia magna: Implications for the evolution of anticipatory maternal effects.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12727-12736}, doi = {10.1002/ece3.4700}, pmid = {30619577}, issn = {2045-7758}, abstract = {Organisms that regularly encounter stressful environments are expected to use cues to develop an appropriate phenotype. Water fleas (Daphnia spp.) are exposed to toxic cyanobacteria during seasonal algal blooms, which reduce growth and reproductive investment. Because generation time is typically shorter than the exposure to cyanobacteria, maternal effects provide information about the local conditions subsequent generations will experience. Here, we evaluate if maternal effects in response to microcystin, a toxin produced by cyanobacteria, represent an inheritance system evolved to transmit information in Daphnia magna. We exposed mothers as juveniles and/or as adults, and tested the offspring's fitness in toxic and non-toxic environments. Maternal exposure until reproduction reduced offspring fitness, both in the presence and in the absence of toxic cyanobacteria. However, this effect was accompanied by a small positive fitness effect, relative to offspring from unexposed mothers, in the presence of toxic cyanobacteria. This effect was mainly elicited in response to maternal exposure to toxic cyanobacteria early in life and less so during reproduction. None of these effects were explained by changes in egg size. A meta-analysis using our and others' experiments suggests that the adaptive value of maternal effects to cyanobacteria exposure is weak at best. We suggest that the beneficial maternal effect in our study is an example of phenotypic accommodation spanning generations, rather than a mechanism evolved to transmit information about cyanobacteria presence between generations.}, } @article {pmid30619576, year = {2018}, author = {Tavalire, HF and Beechler, BR and Buss, PE and Gorsich, EE and Hoal, EG and le Roex, N and Spaan, JM and Spaan, RS and van Helden, PD and Ezenwa, VO and Jolles, AE}, title = {Context-dependent costs and benefits of tuberculosis resistance traits in a wild mammalian host.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12712-12726}, doi = {10.1002/ece3.4699}, pmid = {30619576}, issn = {2045-7758}, support = {UG3 OD023389/OD/NIH HHS/United States ; }, abstract = {Disease acts as a powerful driver of evolution in natural host populations, yet individuals in a population often vary in their susceptibility to infection. Energetic trade-offs between immune and reproductive investment lead to the evolution of distinct life history strategies, driven by the relative fitness costs and benefits of resisting infection. However, examples quantifying the cost of resistance outside of the laboratory are rare. Here, we observe two distinct forms of resistance to bovine tuberculosis (bTB), an important zoonotic pathogen, in a free-ranging African buffalo (Syncerus caffer) population. We characterize these phenotypes as "infection resistance," in which hosts delay or prevent infection, and "proliferation resistance," in which the host limits the spread of lesions caused by the pathogen after infection has occurred. We found weak evidence that infection resistance to bTB may be heritable in this buffalo population (h2 = 0.10) and comes at the cost of reduced body condition and marginally reduced survival once infected, but also associates with an overall higher reproductive rate. Infection-resistant animals thus appear to follow a "fast" pace-of-life syndrome, in that they reproduce more quickly but die upon infection. In contrast, proliferation resistance had no apparent costs and was associated with measures of positive host health-such as having a higher body condition and reproductive rate. This study quantifies striking phenotypic variation in pathogen resistance and provides evidence for a link between life history variation and a disease resistance trait in a wild mammalian host population.}, } @article {pmid30619575, year = {2018}, author = {Downey, H and Lewis, OT and Bonsall, MB and Fernandez, DC and Gripenberg, S}, title = {Insect herbivory on seedlings of rainforest trees: Effects of density and distance of conspecific and heterospecific neighbors.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12702-12711}, doi = {10.1002/ece3.4698}, pmid = {30619575}, issn = {2045-7758}, abstract = {Natural enemies of plants such as insect herbivores can contribute to structuring and maintaining plant diversity in tropical forests. Most research in this area has focused on the role of specialized enemies and the extent to which herbivory on individual plant species is density-dependent. Relatively few insect herbivores specialize on a single host plant species. Insect herbivores that feed on more than one plant species may link the regeneration dynamics of their host species through "apparent competition" or "apparent mutualism." We investigated herbivory and survival of seedlings of two tropical tree species (Cordia alliodora and Cordia bicolor) in the forests of Barro Colorado Island (Panama). We used experiments and observations to assess seedling fate in relation to the presence of conspecifics and heterospecifics across a range of spatial scales. Herbivory significantly increased seedling mortality and was highest at high local densities of C. alliodora seedlings. There was also evidence that high local densities of C. alliodora increased herbivory on co-occurring C. bicolor seedlings. Synthesis. The elevated rates of seedling herbivory at high densities of conspecifics documented in our study are consistent with the predictions of the Janzen-Connell hypothesis, which explains how so many plant species can coexist in tropical forests. Our data also highlight the possibility that herbivore-mediated density-dependence, facilitated by herbivores that feed on multiple plant species, can also occur across plant species. Enemy-mediated indirect effects of this sort have the potential to structure plant communities.}, } @article {pmid30619574, year = {2018}, author = {Huang, XL and Xiao, L and He, HM and Xue, FS}, title = {Effect of rearing conditions on the correlation between larval development time and pupal weight of the rice stem borer, Chilo suppressalis.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12694-12701}, doi = {10.1002/ece3.4697}, pmid = {30619574}, issn = {2045-7758}, abstract = {A strong positive correlation between development time and body size is commonly assumed. However, the evidence is increasing that the correlation between the two traits can be positive, zero or negative, depending on whether the two traits are under antagonistic or synergistic selection. In the present study, we examined the relation between larval development time and pupal weight of the rice stem borer Chilo suppressalis under laboratory and field conditions. For individuals reared at constant temperatures (22, 25, 28 and 31°C), a longer larval period tended to result in larger pupae, showing a positive correlation between larval development time and pupal weight; whereas for those reared under field conditions, a longer larval period tended to result in smaller pupae at 23.5 and 29.8°C, showing a negative correlation between the two traits. There was no correlation between the two traits at the mean daily temperature of 31°C. At constant temperatures, larval development time shortened significantly as rearing temperature increased, whereas pupae tended to become larger at higher temperatures, although no significant difference was detected among temperatures for pupal weight. Under field conditions, larval development time decreased significantly as the mean daily temperature increased, whereas pupal weight of females increased significantly with the increase in the mean daily temperature, which is an example of the reverse temperature-size rule. Feeding method significantly affected larval development time and pupal weight. For individuals fed on live rice plants, larval development time shortened significantly and pupal weight increased significantly compared with those reared on fresh rice stems.}, } @article {pmid30619573, year = {2018}, author = {Batista, MRD and Penha, RES and Sofia, SH and Klaczko, LB}, title = {Comparative analysis of adaptive and neutral markers of Drosophila mediopunctata populations dispersed among forest fragments.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12681-12693}, doi = {10.1002/ece3.4696}, pmid = {30619573}, issn = {2045-7758}, abstract = {Comparison of adaptive and neutral genetic markers is a valuable approach to characterize the evolutionary consequences of populations living in environments threatened by anthropogenic disturbances, such as forest fragmentation. Shifts in allele frequencies, low genetic variability, and a small effective population size can be considered clear signs of forest fragmentation effects (due to genetic drift) over natural populations, while adaptive responses correlate with environmental variables. Brazilian Atlantic Forest had its landscape drastically reduced and fragmented. Now, several forest remnants are isolated from each other by urban and crop areas. We sampled Drosophila mediopunctata populations from eight forest remnants dispersed on two adjacent geomorphological regions, which are physiognomic and climatically quite distinct. Microsatellite data of inversion-free chromosomes (neutral genetic marker) indicate low structuration among populations suggesting that they were panmictic and greatly influenced by gene flow. Moreover, significant differences in chromosomal inversion frequencies (adaptive genetic marker) among populations and their correlations with climatic and geographical variables indicate that genetic divergence among populations could be an adaptive response to their environment. Nonetheless, we observed a significant difference in inversion frequencies of a population in two consecutive years that may be associated with edge and demographic effects. Also, it may be reflecting seasonal changes of inversion frequencies influenced by great temperature variation due to edge effects. Moreover, the forest fragment size does not affect genetic variation of neutral markers. Our data indicate that despite oscillations in chromosomal inversion frequencies, D. mediopunctata populations from Brazilian Atlantic Forest and their divergence may be driven by adaptive factors to local differences, perhaps because it is a small flying insect easily carried by the wind increasing its migration rates.}, } @article {pmid30619572, year = {2018}, author = {Thakur, MP and Griffin, JN and Künne, T and Dunker, S and Fanesi, A and Eisenhauer, N}, title = {Temperature effects on prey and basal resources exceed that of predators in an experimental community.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12670-12680}, doi = {10.1002/ece3.4695}, pmid = {30619572}, issn = {2045-7758}, abstract = {Climate warming alters the structure of ecological communities by modifying species interactions at different trophic levels. Yet, the consequences of warming-led modifications in biotic interactions at higher trophic levels on lower trophic groups are lesser known. Here, we test the effects of multiple predator species on prey population size and traits and subsequent effects on basal resources along an experimental temperature gradient (12-15°C, 17-20°C, and 22-25°C). We experimentally assembled food web modules with two congeneric predatory mites (Hypoaspis miles and Hypoaspis aculeifer) and two Collembola prey species (Folsomia candida and Proisotoma minuta) on a litter and yeast mixture as the basal resources. We hypothesized that warming would modify interactions within and between predator species, and that these alterations would cascade to basal resources via changes in the density and traits (body size and lipid: protein ratio) of the prey species. The presence of congeners constrained the growth of the predatory species independent of warming despite warming increased predator density in their respective monocultures. We found that warming effects on both prey and basal resources were greater than the effects of predator communities. Our results further showed opposite effects of warming on predator (increase) and prey densities (decrease), indicating a warming-induced trophic mismatch, which are likely to alter food web structures. We highlight that warmer environments can restructure food webs by its direct effects on lower trophic groups even without modifying top-down effects.}, } @article {pmid30619571, year = {2018}, author = {Hart, KM and Iverson, AR and Fujisaki, I and Lamont, MM and Bucklin, D and Shaver, DJ}, title = {Sympatry or syntopy? Investigating drivers of distribution and co-occurrence for two imperiled sea turtle species in Gulf of Mexico neritic waters.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12656-12669}, doi = {10.1002/ece3.4691}, pmid = {30619571}, issn = {2045-7758}, abstract = {Animals co-occurring in a region (sympatry) may use the same habitat (syntopy) within that region. A central aim in ecology is determining what factors drive species distributions (i.e., abiotic conditions, dispersal limitations, and/or biotic interactions). Assessing the degree of biotic interactions can be difficult for species with wide ranges at sea. This study investigated the spatial ecology of two sea turtle species that forage on benthic invertebrates in neritic GoM waters: Kemp's ridleys (Lepidochelys kempii) and loggerheads (Caretta caretta). We used satellite tracking and modeled behavioral modes, then calculated individual home ranges, compared foraging areas, and determined extent of co-occurrence. Using six environmental variables and principal component analysis, we assessed similarity of chosen foraging sites. We predicted foraging location (eco-region) based on species, nesting site, and turtle size. For 127 turtles (64 Kemp's ridleys, 63 loggerheads) tracked from 1989 to 2013, foraging home ranges were nine to ten times larger for Kemp's ridleys than for loggerheads. Species intersected off all U.S. coasts and the Yucatán Peninsula, but co-occurrence areas were small compared to species' distributions. Kemp's ridley foraging home ranges were concentrated in the northern GoM, whereas those for loggerheads were concentrated in the eastern GoM. The two species were different in all habitat variables compared (latitude, longitude, distance to shore, net primary production, mean sea surface temperature, and bathymetry). Nesting site was the single dominant variable that dictated foraging ecoregion. Although Kemp's ridleys and loggerheads may compete for resources, the separation in foraging areas, significant differences in environmental conditions, and importance of nesting location on ecoregion selection (i.e., dispersal ability) indicate that adult females of these species do not interact greatly during foraging and that dispersal and environmental factors more strongly determine their distributions. These species show sympatry in this region but evidence for syntopy was rare.}, } @article {pmid30619570, year = {2018}, author = {Heppenheimer, E and Brzeski, KE and Hinton, JW and Patterson, BR and Rutledge, LY and DeCandia, AL and Wheeldon, T and Fain, SR and Hohenlohe, PA and Kays, R and White, BN and Chamberlain, MJ and vonHoldt, BM}, title = {High genomic diversity and candidate genes under selection associated with range expansion in eastern coyote (Canis latrans) populations.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12641-12655}, doi = {10.1002/ece3.4688}, pmid = {30619570}, issn = {2045-7758}, abstract = {Range expansion is a widespread biological process, with well-described theoretical expectations associated with the colonization of novel ranges. However, comparatively few empirical studies address the genomic outcomes accompanying the genome-wide consequences associated with the range expansion process, particularly in recent or ongoing expansions. Here, we assess two recent and distinct eastward expansion fronts of a highly mobile carnivore, the coyote (Canis latrans), to investigate patterns of genomic diversity and identify variants that may have been under selection during range expansion. Using a restriction-associated DNA sequencing (RADseq), we genotyped 394 coyotes at 22,935 SNPs and found that overall population structure corresponded to their 19th century historical range and two distinct populations that expanded during the 20th century. Counter to theoretical expectations for populations to bottleneck during range expansions, we observed minimal evidence for decreased genomic diversity across coyotes sampled along either expansion front, which is likely due to hybridization with other Canis species. Furthermore, we identified 12 SNPs, located either within genes or putative regulatory regions, that were consistently associated with range expansion. Of these 12 genes, three (CACNA1C, ALK, and EPHA6) have putative functions related to dispersal, including habituation to novel environments and spatial learning, consistent with the expectations for traits under selection during range expansion. Although coyote colonization of eastern North America is well-publicized, this study provides novel insights by identifying genes associated with dispersal capabilities in coyotes on the two eastern expansion fronts.}, } @article {pmid30619569, year = {2018}, author = {Larue, B and Côté, SD and St-Laurent, MH and Dussault, C and Leblond, M}, title = {Natal habitat preference induction in large mammals-Like mother, like child?.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12629-12640}, doi = {10.1002/ece3.4685}, pmid = {30619569}, issn = {2045-7758}, abstract = {Habitat selection has received considerable attention from ecologists during the last decades, yet the underlying forces shaping individual differences in habitat selection are poorly documented. Some of these differences could be explained by the early experience of individuals in their natal habitat. By selecting habitat attributes like those encountered early in life, individuals could improve resource acquisition, survival, and ultimately fitness. This behavior, known as natal habitat preference induction (NHPI), could be particularly common in large mammals, because offspring generally stay with their mother for an extended period. We used three complementary approaches to assess NHPI in a marked population of woodland caribou (Rangifer tarandus caribou): (a) population-based resource selection functions (RSFs), (b) individual-based RSFs, and (c) behavioral repeatability analyses. All approaches compared the behavior of calves in their natal range to their behavior as independent subadults during the snow-covered (Dec-Apr) and snow-free (May-Nov) seasons. Using RSFs, we found that the magnitude of habitat selection between calf and subadult stages differed for most covariates, yet the signs of statistically significant effects (selection vs. avoidance) were generally the same. We also found that some habitat selection tactics were highly repeatable across life stages. Notably, caribou responses to habitat disturbances were highly repeatable year-round, meaning that different individuals reacted differently, but consistently, to disturbances. This study highlights the potential role of natal habitat preference induction in shaping individual differences in habitat selection in large mammals and provides valuable knowledge for the management and conservation of a threatened species.}, } @article {pmid30619568, year = {2018}, author = {de Lima, HS and Las-Casas, FMG and Ribeiro, JR and Gonçalves-Souza, T and Naka, LN}, title = {Ecological and phylogenetic predictors of mobbing behavior in a tropical dry forest.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12615-12628}, doi = {10.1002/ece3.4683}, pmid = {30619568}, issn = {2045-7758}, abstract = {Mobbing represents a well-known anti-predatory behavior, where potential prey display aggressively against a predator. Despite considerable experimental and descriptive work, no models predict species participation in mobbing assemblages. Here, we aimed to understand why some bird species engage in this behavior, while others do not, and what factors can be used to predict mobbing engagement within an avian community. We investigated whether certain functional traits, such as body size, foraging guild, foraging mode, and strata, as well species abundance and evolutionary relatedness, are important mobbing predictors. To address these goals, we simulated the presence of the Ferruginous Pygmy-Owl (Glaucidium brasilianum) by broadcasting its voice in 230 experiments conducted in 115 points, systematically distributed in a dry forest of northeastern Brazil. We compared these results to 162 avian surveys (point counts) conducted in the same area. Our avian surveys detected 108 bird species (local avian community), whereas our playback experiments attracted 72 species (mobbing assemblage). In general, small, canopy insectivorous or frugivorous birds dominated the mobs. The best mobbing predictors were body mass and guild, whereas species abundance, foraging mode, and strata were not retained in the best models. We found a strong phylogenetic component in body mass and mobbing propensity (almost 90% of the species and individuals participating in the mobs were passerines). At the community level, we found significant differences in the functional and phylogenetic structure of the mobbing assemblage in relation to the avian community. Our results suggest that mobbing behavior is tightly associated with predation risk and the capacity of individual species to find and detect predators, and that functional and phylogenetic features can predict species participation in this complex animal behavior.}, } @article {pmid30619567, year = {2018}, author = {Genoves, RC and Fruet, PF and Di Tullio, JC and Möller, LM and Secchi, ER}, title = {Spatiotemporal use predicts social partitioning of bottlenose dolphins with strong home range overlap.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12597-12614}, doi = {10.1002/ece3.4681}, pmid = {30619567}, issn = {2045-7758}, abstract = {Ranging behaviour and temporal patterns of individuals are known to be fundamental sources of variation in social networks. Spatiotemporal dynamics can both provide and inhibit opportunities for individuals to associate, and should therefore be considered in social analysis. This study investigated the social structure of a Lahille's bottlenose dolphin (Tursiops truncatus gephyreus) population, which shows different spatiotemporal patterns of use and gregariousness between individuals. For this, we constructed an initial social network using association indices corrected for gregariousness and then uncovered affiliations from this social network using generalized affiliation indices. The association-based social network strongly supported that this dolphin population consists of four social units highly correlated to spatiotemporal use patterns. Excluding the effects of gregariousness and spatiotemporal patterns, the affiliation-based social network suggested an additional two social units. Although the affiliation-based social units shared a large part of their core areas, space and/or time use by individuals of the different units were generally distinct. Four of the units were strongly associated with both estuarine and shallow coastal areas, while the other two units were restricted to shallow coastal waters to the south (SC) and north of the estuary (NC), respectively. Interactions between individuals of different social units also occurred, but dolphins from the NC were relatively more isolated and mainly connected to SC dolphins. From a conservation management perspective, it is recommended that information about the dolphin social units should be incorporated in modeling intrapopulation dynamics and viability, as well as for investigating patterns of gene flow among them.}, } @article {pmid30619566, year = {2018}, author = {Lazzeroni, ME and Burbrink, FT and Simmons, NB}, title = {Hibernation in bats (Mammalia: Chiroptera) did not evolve through positive selection of leptin.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12576-12596}, doi = {10.1002/ece3.4674}, pmid = {30619566}, issn = {2045-7758}, abstract = {Temperature regulation is an indispensable physiological activity critical for animal survival. However, relatively little is known about the origin of thermoregulatory regimes in a phylogenetic context, or the genetic mechanisms driving the evolution of these regimes. Using bats as a study system, we examined the evolution of three thermoregulatory regimes (hibernation, daily heterothermy, and homeothermy) in relation to the evolution of leptin, a protein implicated in regulation of torpor bouts in mammals, including bats. A threshold model was used to test for a correlation between lineages with positively selected lep, the gene encoding leptin, and the thermoregulatory regimes of those lineages. Although evidence for episodic positive selection of lep was found, positive selection was not correlated with lineages of heterothermic bats, a finding that contradicts results from previous studies. Evidence from our ancestral state reconstructions suggests that the most recent common ancestor of bats used daily heterothermy and that the presence of hibernation is highly unlikely at this node. Hibernation likely evolved independently at least four times in bats-once in the common ancestor of Vespertilionidae and Molossidae, once in the clade containing Rhinolophidae and Rhinopomatidae, and again independently in the lineages leading to Taphozous melanopogon and Mystacina tuberculata. Our reconstructions revealed that thermoregulatory regimes never transitioned directly from hibernation to homeothermy, or the reverse, in the evolutionary history of bats. This, in addition to recent evidence that heterothermy is best described along a continuum, suggests that thermoregulatory regimes in mammals are best represented as an ordered continuous trait (homeothermy ← → daily torpor ← → hibernation) rather than as the three discrete regimes that evolve in an unordered fashion. These results have important implications for methodological approaches in future physiological and evolutionary research.}, } @article {pmid30619565, year = {2018}, author = {García-Morales, E and Carrillo-Ángeles, IG and Golubov, J and Piñero, D and Mandujano, MC}, title = {Influence of fruit dispersal on genotypic diversity and migration rates of a clonal cactus from the Chihuahuan Desert.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12559-12575}, doi = {10.1002/ece3.4657}, pmid = {30619565}, issn = {2045-7758}, abstract = {The diverse offspring of clonal species differ in their dispersability, influencing genotypic diversity and clonal structure. Here, we determined dispersal patterns and their impact on genetic structure in Opuntia microdasys, a self-incompatible cactus with three dispersal units (one sexual and two clonal). We analyzed dispersal, using experiments at three populations, and assessed multilocus genotypes (ISSR markers) of all individuals in 10 clumps per population with known reproductive origin (sexual or clonal). Genotype of all samples, population structure, and migration between clumps and populations were assessed with GenAlEx and GenoDive, assuming higher genotypic diversity and migration when sexual reproduction is more frequent. We determined the most likely number of genetic clusters with STRUCTURE and geneland. Dispersal differed among populations; primary dispersal occurred at short distances and was farthest on steep slopes, and dispersal distance increased after secondary dispersal. Clumps had 116 different multilocus genotypes in three spatially explicit genetic clusters. We detected genetic structure at small scale, genotypic diversity among clumps varied between populations; diversity decreased while clonal dominance increased, and the most variation occurred among clumps. Genetic structure was moderate, suggesting gene flow by seed dispersal allows slight differentiation among population at large scales. Genetic diversity within clumps was the lowest because dispersal of clonal propagules was limited and caused genotypic dominance at local scale. However, the combined dispersal pattern of sexual and clonal dispersal units is fine-tuned by environmental factors, generating a range of genetic diversity among clusters and populations. This pattern suggests that genetic structure of clonal plants is more dynamic than thought, and dispersal of different types of offspring affects genetic structure at many scales.}, } @article {pmid30619564, year = {2018}, author = {Jorde, PE and Synnes, AE and Espeland, SH and Sodeland, M and Knutsen, H}, title = {Can we rely on selected genetic markers for population identification? Evidence from coastal Atlantic cod.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12547-12558}, doi = {10.1002/ece3.4648}, pmid = {30619564}, issn = {2045-7758}, abstract = {The use of genetic markers under putative selection in population studies carries the potential for erroneous identification of populations and misassignment of individuals to population of origin. Selected markers are nevertheless attractive, especially in marine organisms that are characterized by weak population structure at neutral loci. Highly fecund species may tolerate the cost of strong selective mortality during early life stages, potentially leading to a shift in offspring genotypes away from the parental proportions. In Atlantic cod, recent genetic studies have uncovered different genotype clusters apparently representing phenotypically cryptic populations that coexist in coastal waters. Here, we tested if a high-graded SNP panel specifically designed to classify individual cod to population of origin may be unreliable because of natural selection acting on the SNPs or their linked background. Temporal samples of cod were collected from two fjords, starting at the earliest life stage (pelagic eggs) and carried on until late autumn (bottom-settled juveniles), covering the period during summer of high natural mortality. Despite the potential for selective mortality during the study period, we found no evidence for selection, as both cod types occurred throughout the season, already in the earliest egg samples, and there was no evidence for a shift during the season in the proportions of one or the other type. We conclude that high-graded marker panels under putative natural selection represent a valid and useful tool for identifying biological population structure in this highly fecund species and presumably in others.}, } @article {pmid30619563, year = {2018}, author = {Porensky, LM and Perryman, BL and Williamson, MA and Madsen, MD and Leger, EA}, title = {Combining active restoration and targeted grazing to establish native plants and reduce fuel loads in invaded ecosystems.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12533-12546}, doi = {10.1002/ece3.4642}, pmid = {30619563}, issn = {2045-7758}, abstract = {Many drylands have been converted from perennial-dominated ecosystems to invaded, annual-dominated, fire-prone systems. Innovative approaches are needed to disrupt fire-invasion feedbacks. Targeted grazing can reduce invasive plant abundance and associated flammable fuels, and fuelbreaks can limit fire spread. Restored strips of native plants (native greenstrips) can function as fuelbreaks while also providing forage and habitat benefits. However, methods for establishing native greenstrips in invaded drylands are poorly developed. Moreover, if fuels reduction and greenstrip establishment are to proceed simultaneously, it is critical to understand how targeted grazing interacts with plant establishment. We determined how targeted grazing treatments interacted with seed rate, spatial planting arrangement (mixtures vs. monoculture strips), seed coating technology, and species identity (five native grasses) to affect standing biomass and seeded plant density in experimental greenstrips. We monitored for two growing seasons to document effects during the seedling establishment phase. Across planting treatments, ungrazed paddocks had the highest second-year seeded plant densities and the highest standing biomass. Paddocks grazed in fall of the second growing season had fewer seedlings than paddocks grazed in spring, five months later. High seed rates minimized negative effects of grazing on plant establishment. Among seeded species, Elymus trachycaulus and Poa secunda had the highest second-year densities, but achieved this via different pathways. Elymus trachycaulus produced the most first-year seedlings, but declined in response to grazing, whereas P. secunda had moderate first-year establishment but high survival across grazing treatments. We identified clear tradeoffs between reducing fuel loads and establishing native plants in invaded sagebrush steppe; similar tradeoffs may exist in other invaded drylands. In our system, tradeoffs were minimized by boosting seed rates, using grazing-tolerant species, and delaying grazing. In invaded ecosystems, combining targeted grazing with high-input restoration may create opportunities to limit wildfire risk while also shifting vegetation toward more desirable species.}, } @article {pmid30619562, year = {2018}, author = {Philson, C and Ray, A and Foltz, S and Davis, J}, title = {Programmable Automated System for Songbird Ecobehavioral Research (PASSER): Using flexible computer-integrated feeders to conduct high resolution studies of environment-behavior dynamics in songbirds.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12522-12532}, doi = {10.1002/ece3.4638}, pmid = {30619562}, issn = {2045-7758}, abstract = {Field studies seeking to identify interactions between the environment and behaviors of wild songbirds are often restricted by time, labor, and accessibility of the site; hampering the collection of long-term, high-resolution data. Here, we describe the development, utilization, and initial results of a long-term field study of wild songbird feeding patterns using data collected through an inexpensive microcomputer-controlled automated feeder. Our studies indicate the "smart feeder" is capable of reliable and accurate data collection on feeding and behavioral metrics over long durations with relation to a wide range of environmental conditions. This enables detailed analysis of songbird's environment-behavior interactions. Our results have identified trends in environment-behavior interactions, microhabitat variations, species-specific feeding profiles, and differences in the frequency and involvement of displacement events. Computerized feeders enabled us to address environment-behavior interactions, resulting in more detailed data than traditional observational methods. This reinforces conclusions from previous work regarding the potential for automated data collection to be adapted for a wide variety of research studies across the field of ethology.}, } @article {pmid30619561, year = {2018}, author = {Tee, SL and Samantha, LD and Kamarudin, N and Akbar, Z and Lechner, AM and Ashton-Butt, A and Azhar, B}, title = {Urban forest fragmentation impoverishes native mammalian biodiversity in the tropics.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12506-12521}, doi = {10.1002/ece3.4632}, pmid = {30619561}, issn = {2045-7758}, abstract = {Urban expansion has caused major deforestation and forest fragmentation in the tropics. The impacts of habitat fragmentation on biodiversity are understudied in urban forest patches, especially in the tropics and little is known on the conservation value of the patches for maintaining mammalian biodiversity. In this study, camera trapping was used to determine the species composition and species richness of medium- and large-sized mammals in three urban forest patches and a contiguous forest in Peninsular Malaysia. We identified the key vegetation attributes that predicted mammal species richness and occurrence of herbivores and omnivores in urban forest patches. A total number of 19 mammal species from 120 sampling points were recorded. Contiguous forest had the highest number of species compared to the urban forest patches. Sunda Pangolin and Asian Tapir were the only conservation priority species recorded in the urban forest patches and contiguous forest, respectively. Top predators such as Malayan Tiger and Melanistic Leopard were completely absent from the forest patches as well as the contiguous forest. This was reflected by the abundance of wild boars. We found that mammal species richness increased with the number of trees with DBH less than 5 cm, trees with DBH more than 50 cm, and dead standing trees. In the future, the remaining mammal species in the urban forest patches are expected to be locally extinct as connecting the urban forest patches may be infeasible due to land scarcity. Hence, to maintain the ecological integrity of urban forest patches, we recommend that stakeholders take intervention measures such as reintroduction of selected species and restocking of wild populations in the urban forest patches to regenerate the forest ecosystems.}, } @article {pmid30619560, year = {2018}, author = {Donnelly, JP and Allred, BW and Perret, D and Silverman, NL and Tack, JD and Dreitz, VJ and Maestas, JD and Naugle, DE}, title = {Seasonal drought in North America's sagebrush biome structures dynamic mesic resources for sage-grouse.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12492-12505}, doi = {10.1002/ece3.4614}, pmid = {30619560}, issn = {2045-7758}, abstract = {The North American semi-arid sagebrush, Artemisia spp., biome exhibits considerable climatic complexity driving dynamic spatiotemporal shifts in primary productivity. Greater and Gunnison sage-grouse, Centrocercus urophasianus and C. minimus, are adapted to patterns of resource intermittence and rely on stable adult survival supplemented by occasional recruitment pulses when climatic conditions are favorable. Predictions of intensifying water scarcity raise concerns over new demographic bottlenecks impacting sage-grouse populations in drought-sensitive landscapes. We estimate biome-wide mesic resource productivity from 1984 to 2016 using remote sensing to identify patterns of food availability influencing selective pressures on sage-grouse. We linked productivity to abiotic factors to examine effects of seasonal drought across time, space, and land tenure, with findings partitioned along gradients of ecosystem water balance within Great Basin, Rocky Mountains and Great Plains regions. Precipitation was the driver of mesic resource abundance explaining ≥70% of variance in drought-limited vegetative productivity. Spatiotemporal shifts in mesic abundance were apparent given biome-wide climatic trends that reduced precipitation below three-quarters of normal in 20% of years. Drought sensitivity structured grouse populations wherein landscapes with the greatest uncertainty in mesic abundance and distribution supported the fewest grouse. Privately owned lands encompassed 40% of sage-grouse range, but contained a disproportional 68% of mesic resources. Regional drought sensitivity identified herein acted as ecological minimums to influence differences in landscape carrying capacity across sage-grouse range. Our model depictions likely reflect a new normal in water scarcity that could compound impacts of demographic bottlenecks in Great Basin and Great Plains. We conclude that long-term population maintenance depends on a diversity of drought resistant mesic resources that offset climate driven variability in vegetative productivity. We recommend a holistic public-private lands approach to mesic restoration to offset a deepening risk of water scarcity.}, } @article {pmid30619559, year = {2018}, author = {Tng, DYP and Apgaua, DMG and Ishida, YF and Mencuccini, M and Lloyd, J and Laurance, WF and Laurance, SGW}, title = {Rainforest trees respond to drought by modifying their hydraulic architecture.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12479-12491}, doi = {10.1002/ece3.4601}, pmid = {30619559}, issn = {2045-7758}, abstract = {Increased drought is forecasted for tropical regions, with severe implications for the health and function of forest ecosystems. How mature forest trees will respond to water deficit is poorly known. We investigated wood anatomy and leaf traits in lowland tropical forest trees after 24 months of experimental rainfall exclusion. Sampling sun-exposed young canopy branches from target species, we found species-specific systematic variation in hydraulic-related wood anatomy and leaf traits in response to drought stress. Relative to controls, drought-affected individuals of different tree species variously exhibited trait measures consistent with increasing hydraulic safety. These included narrower or less vessels, reduced vessel groupings, lower theoretical water conductivities, less water storage tissue and more abundant fiber in their wood, and more occluded vessels. Drought-affected individuals also had thinner leaves, and more negative pre-dawn or mid-day leaf water potentials. Future studies examining both wood and leaf hydraulic traits should improve the representation of plant hydraulics within terrestrial ecosystem and biosphere models, and help fine-tune predictions of how future climate changes will affect tropical forests globally.}, } @article {pmid30619558, year = {2018}, author = {Provost, KL and Mauck, WM and Smith, BT}, title = {Genomic divergence in allopatric Northern Cardinals of the North American warm deserts is linked to behavioral differentiation.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12456-12478}, doi = {10.1002/ece3.4596}, pmid = {30619558}, issn = {2045-7758}, abstract = {Biogeographic barriers are considered important in initiating speciation through geographic isolation, but they rarely indiscriminately and completely reduce gene flow across entire communities. Explicitly demonstrating which factors are associated with gene-flow levels across barriers would help elucidate how speciation is initiated and isolation maintained. Here, we investigated the association of behavioral isolation on population differentiation in Northern Cardinals (Cardinalis cardinalis) distributed across the Cochise Filter Barrier, a region of transitional habitat which separates the Sonoran and Chihuahuan deserts of North America. Using genomewide markers, we modeled demographic history by fitting the data to isolation and isolation-with-migration models. The best-fit model indicated that desert populations diverged in the Pleistocene with low, historic, and asymmetric gene flow across the barrier. We then tested behavioral isolation using reciprocal call-broadcast experiments to compare song recognition between deserts, controlling for song dialect changes within deserts. We found that male Northern Cardinals in both deserts were most aggressive to local songs and failed to recognize across-barrier songs. A correlation of genomic differentiation and strong song discrimination is consistent with a model where speciation is initiated across a barrier and maintained by behavioral isolation.}, } @article {pmid30619557, year = {2018}, author = {Duplouy, A and Minard, G and Lähteenaro, M and Rytteri, S and Saastamoinen, M}, title = {Silk properties and overwinter survival in gregarious butterfly larvae.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12443-12455}, doi = {10.1002/ece3.4595}, pmid = {30619557}, issn = {2045-7758}, abstract = {All organisms are challenged by encounters with parasites, which strongly select for efficient escape strategies in the host. The threat is especially high for gregarious species entering immobile periods, such as diapause. Larvae of the Glanville fritillary butterfly, Melitaea cinxia, spend the winter in diapause in groups of conspecifics each sheltered in a silk nest. Despite intensive monitoring of the population, we have little understanding of the ecological factors influencing larval survival over the winter in the field. We tested whether qualitative and quantitative properties of the silk nest contribute to larval survival over diapause. We used comparative proteomics, metabarcoding analyses, microscopic imaging, and in vitro experiments to compare protein composition of the silk, community composition of the silk-associated microbiota, and silk density from both wild-collected and laboratory-reared families, which survived or died in the field. Although most traits assessed varied across families, only silk density was correlated with overwinter survival in the field. The silk nest spun by gregarious larvae before the winter acts as an efficient breathable physical shield that positively affects larval survival during diapause. Such benefit may explain how this costly trait is conserved across populations of this butterfly species and potentially across other silk-spinning insect species.}, } @article {pmid30619556, year = {2018}, author = {Griffin, JN and Silliman, BR}, title = {Predator size-structure and species identity determine cascading effects in a coastal ecosystem.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12435-12442}, doi = {10.1002/ece3.4571}, pmid = {30619556}, issn = {2045-7758}, abstract = {Cascading consequences of predator extinctions are well documented, but impacts of perturbations to predator size-structure and how these vary across species remain unclear. Body size is hypothesized to be a key trait governing individual predators' impact on ecosystems. Therefore, shifts in predator size-structure should trigger ecosystem ramifications which are consistent across functionally similar species. Using a US salt marsh as a model system, we tested this hypothesis by manipulating size class (small, medium, and large) and size diversity (combination of all three size classes) within two closely related and functionally similar predatory crab species over 4 months. Across treatments, predators suppressed densities of a dominant grazer and an ecosystem engineer, enhanced plant biomass, and altered sediment properties (redox potential and saturation). Over the metabolically equivalent experimental predator treatments, small size class predators had stronger average impacts on response variables, and size class interacted with predator species identity to drive engineer suppression. Within both predator species, size diversity increased cannibalism and slightly weakened the average impact. These results show that predator impacts in a salt marsh ecosystem are determined by both size class and size diversity; they also highlight that size class can have species-dependent and response-dependent effects, underlining the challenge of generalizing trait effects.}, } @article {pmid30619555, year = {2018}, author = {Barraquand, F and Nielsen, ÓK}, title = {Predator-prey feedback in a gyrfalcon-ptarmigan system?.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12425-12434}, doi = {10.1002/ece3.4563}, pmid = {30619555}, issn = {2045-7758}, abstract = {Specialist predators with oscillating dynamics are often strongly affected by the population dynamics of their prey, yet they are not always the cause of prey cycling. Only those that exert strong (delayed) regulation of their prey can be. Inferring predator-prey coupling from time series therefore requires contrasting models with top-down versus bottom-up predator-prey dynamics. We study here the joint dynamics of population densities of the Icelandic gyrfalcon Falco rusticolus, and its prey, the rock ptarmigan Lagopus muta. The dynamics of both species are likely not only linked to each other but also to stochastic weather variables acting as confounding factors. We infer the degree of coupling between populations, as well as forcing by abiotic variables, using multivariate autoregressive models MAR(p), with p = 1 and 2 time lags. MAR(2) models, allowing for species to cycle independently from each other, further suggest alternative scenarios where a cyclic prey influences its predator but not the other way around (i.e., bottom-up scenarios). The classical MAR(1) model predicts that the time series exhibit predator-prey feedback (i.e., reciprocal dynamic influence between prey and predator), and that weather effects are weak and only affecting the gyrfalcon population. Bottom-up MAR(2) models produced a better fit but less realistic cross-correlation patterns. Simulations of MAR(1) and MAR(2) models further demonstrate that the top-down MAR(1) models are more likely to be misidentified as bottom-up dynamics than vice versa. We therefore conclude that predator-prey feedback in the gyrfalcon-ptarmigan system is likely the main cause of observed oscillations, though bottom-up dynamics cannot yet be excluded with certainty. Overall, we showed how to make more out of ecological time series by using simulations to gauge the quality of model identification, and paved the way for more mechanistic modeling of this system by narrowing the set of important biotic and abiotic drivers.}, } @article {pmid30619554, year = {2018}, author = {Koutroumpa, K and Theodoridis, S and Warren, BH and Jiménez, A and Celep, F and Doğan, M and Romeiras, MM and Santos-Guerra, A and Fernández-Palacios, JM and Caujapé-Castells, J and Moura, M and Menezes de Sequeira, M and Conti, E}, title = {An expanded molecular phylogeny of Plumbaginaceae, with emphasis on Limonium (sea lavenders): Taxonomic implications and biogeographic considerations.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12397-12424}, doi = {10.1002/ece3.4553}, pmid = {30619554}, issn = {2045-7758}, abstract = {Plumbaginaceae is characterized by a history of multiple taxonomic rearrangements and lacks a broad molecular phylogenetic framework. Limonium is the most species-rich genus of the family with ca. 600 species and cosmopolitan distribution. Its center of diversity is the Mediterranean region, where ca. 70% of all Limonium species are endemic. In this study, we sample 201 Limonium species covering all described infrageneric entities and spanning its wide geographic range, along with 64 species of other Plumbaginaceae genera, representing 23 out of 29 genera of the family. Additionally, 20 species of the sister family Polygonaceae were used as outgroup. Sequences of three chloroplast (trnL-F, matK, and rbcL) and one nuclear (ITS) loci were used to infer the molecular phylogeny employing maximum likelihood and Bayesian analyses. According to our results, within Plumbaginoideae, Plumbago forms a non-monophyletic assemblage, with Plumbago europaea sister to Plumbagella, while the other Plumbago species form a clade sister to Dyerophytum. Within Limonioideae, Ikonnikovia is nested in Goniolimon, rejecting its former segregation as genus distinct from Goniolimon. Limonium is divided into two major clades: Limonium subg. Pteroclados s.l., including L. sect. Pteroclados and L. anthericoides, and L. subg. Limonium. The latter is divided into three well-supported subclades: the monospecific L. sect. Limoniodendron sister to a clade comprising a mostly non-Mediterranean subclade and a Mediterranean subclade. Our results set the foundation for taxonomic proposals on sections and subsections of Limonium, namely: (a) the newly described L. sect. Tenuiramosum, created to assign L. anthericoides at the sectional rank; (b) the more restricted circumscriptions of L. sect. Limonium (= L. sect. Limonium subsect. Genuinae) and L. sect. Sarcophyllum (for the Sudano-Zambezian/Saharo-Arabian clade); (c) the more expanded circumscription of L. sect. Nephrophyllum (including species of the L. bellidifolium complex); and (d) the new combinations for L. sect. Pruinosum and L. sect. Pteroclados subsect. Odontolepideae and subsect. Nobiles.}, } @article {pmid30619553, year = {2018}, author = {Hagmayer, A and Furness, AI and Reznick, DN and Pollux, BJA}, title = {Maternal size and body condition predict the amount of post-fertilization maternal provisioning in matrotrophic fish.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12386-12396}, doi = {10.1002/ece3.4542}, pmid = {30619553}, issn = {2045-7758}, abstract = {Maternal effects often provide a mechanism for adaptive transgenerational phenotypic plasticity. The maternal phenotype can profoundly influence the potential for such environmentally induced adjustments of the offspring phenotype, causing correlations between offspring and maternal traits. Here, we study potential effects of the maternal phenotype on offspring provisioning prior to and during gestation in the matrotrophic live-bearing fish species Poeciliopsis retropinna. Specifically, we examine how maternal traits such as body fat, lean mass, and length relate to pre- (i.e., allocation to the egg prior to fertilization) and post-fertilization (i.e., allocation to the embryo during pregnancy) maternal provisioning and how this ultimately affects offspring size and body composition at birth. We show that pre- and post-fertilization maternal provisioning is associated with maternal length and body fat, but not with maternal lean mass. Maternal length is proportionally associated with egg mass at fertilization and offspring mass at birth, notably without changing the ratio of pre- to post-fertilization maternal provisioning. This ratio, referred to as the matrotrophy index (MI), is often used to quantify the level of matrotrophy. By contrast, the proportion of maternal body fat is positively associated with post-fertilization, but not pre-fertilization, maternal provisioning and consequently is strongly positively correlated with the MI. We furthermore found that the composition of embryos changes throughout pregnancy. Females invest first in embryo lean mass, and then allocate fat reserves to embryos very late in pregnancy. We argue that this delay in fat allocation may be adaptive, because it delays an unnecessary high reproductive burden to the mother during earlier stages of pregnancy, potentially leading to a more slender body shape and improved locomotor performance. In conclusion, our study suggests that (a) offspring size at birth is a plastic trait that is predicted by both maternal length and body fat, and (b) the MI is a plastic trait that is predicted solely by the proportion of maternal body fat. It herewith provides new insights into the potential maternal causes and consequences of embryo provisioning during pregnancy in matrotrophic live-bearing species.}, } @article {pmid30619552, year = {2018}, author = {Buckley, LB and Khaliq, I and Swanson, DL and Hof, C}, title = {Does metabolism constrain bird and mammal ranges and predict shifts in response to climate change?.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12375-12385}, doi = {10.1002/ece3.4537}, pmid = {30619552}, issn = {2045-7758}, abstract = {Mechanistic approaches for predicting the ranges of endotherms are needed to forecast their responses to environmental change. We test whether physiological constraints on maximum metabolic rate and the factor by which endotherms can elevate their metabolism (metabolic expansibility) influence cold range limits for mammal and bird species. We examine metabolic expansibility at the cold range boundary (MECRB) and whether species' traits can predict variability in MECRB and then use MECRB as an initial approach to project range shifts for 210 mammal and 61 bird species. We find evidence for metabolic constraints: the distributions of metabolic expansibility at the cold range boundary peak at similar values for birds (2.7) and mammals (3.2). The right skewed distributions suggest some species have adapted to elevate or evade metabolic constraints. Mammals exhibit greater skew than birds, consistent with their diverse thermoregulatory adaptations and behaviors. Mammal and bird species that are small and occupy low trophic levels exhibit high levels of MECRB. Mammals with high MECRB tend to hibernate or use torpor. Predicted metabolic rates at the cold range boundaries represent large energetic expenditures (>50% of maximum metabolic rates). We project species to shift their cold range boundaries poleward by an average of 3.9° latitude by 2070 if metabolic constraints remain constant. Our analysis suggests that metabolic constraints provide a viable mechanism for initial projections of the cold range boundaries for endotherms. However, errors and approximations in estimating metabolic constraints (e.g., acclimation responses) and evasion of these constraints (e.g., torpor/hibernation, microclimate selection) highlight the need for more detailed, taxa-specific mechanistic models. Even coarse considerations of metabolism will likely lead to improved predictions over exclusively considering thermal tolerance for endotherms.}, } @article {pmid30619551, year = {2018}, author = {Reiner Brodetzki, T and Hefetz, A}, title = {Determining social and population structures requires multiple approaches: A case study of the desert ant Cataglyphis israelensis.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12365-12374}, doi = {10.1002/ece3.4535}, pmid = {30619551}, issn = {2045-7758}, abstract = {The remarkable diversity of ant social organization is reflected in both their life history and population kin structure. Different species demonstrate a high variation with respect to both social structure and mating strategies: from the ancestral colony type that is composed of a single queen (monogyny), singly inseminated (monoandry), to the more derived states of colonies headed by a multiply inseminated queen (polyandry), to colonies composed of multiple queens (polygyny) that are either singly or multiply inseminated. Moreover, the population structure of an ant species can range from multicoloniality to polydomy to supercoloniality, and Cataglyphis is considered to be a model genus in regard to such diversity. The present study sought to determine the social and population structure of the recently described C. israelensis species in Israel. For this purpose we employed a multidisciplinary approach, rather than the commonly used single approach that is mostly based on genetics. Our study encompassed behavior (nest insularity/openness), chemistry (composition of nestmate recognition signals and cuticular hydrocarbons), and genetics (microsatellite polymorphism). Each approach has been shown to possess both advantages and disadvantages, depending on the studied species. Our findings reveal that C. israelensis colonies are headed by a single, multiply inseminated queen and that the population structure is polydomous, with each colony comprising one main nest and several additional satellite nests. Moreover, our findings demonstrate that none of the above-noted approaches, when employed individually, is suitable or sufficient in itself for delineating population structure, thus emphasizing the importance of using multiple approaches when assessing such complex systems.}, } @article {pmid30619550, year = {2018}, author = {Pfeiffer, VW and Ford, BM and Housset, J and McCombs, A and Blanco-Pastor, JL and Gouin, N and Manel, S and Bertin, A}, title = {Partitioning genetic and species diversity refines our understanding of species-genetic diversity relationships.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12351-12364}, doi = {10.1002/ece3.4530}, pmid = {30619550}, issn = {2045-7758}, abstract = {Disentangling the origin of species-genetic diversity correlations (SGDCs) is a challenging task that provides insight into the way that neutral and adaptive processes influence diversity at multiple levels. Genetic and species diversity are comprised by components that respond differently to the same ecological processes. Thus, it can be useful to partition species and genetic diversity into their different components to infer the mechanisms behind SGDCs. In this study, we applied such an approach using a high-elevation Andean wetland system, where previous evidence identified neutral processes as major determinants of the strong and positive covariation between plant species richness and AFLP genetic diversity of the common sedge Carex gayana. To tease apart putative neutral and non-neutral genetic variation of C. gayana, we identified loci putatively under selection from a dataset of 1,709 SNPs produced using restriction site-associated DNA sequencing (RAD-seq). Significant and positive relationships between local estimates of genetic and species diversities (α-SGDCs) were only found with the putatively neutral loci datasets and with species richness, confirming that neutral processes were primarily driving the correlations and that the involved processes differentially influenced local species diversity components (i.e., richness and evenness). In contrast, SGDCs based on genetic and community dissimilarities (β-SGDCs) were only significant with the putative non-neutral datasets. This suggests that selective processes influencing C. gayana genetic diversity were involved in the detected correlations. Together, our results demonstrate that analyzing distinct components of genetic and species diversity simultaneously is useful to determine the mechanisms behind species-genetic diversity relationships.}, } @article {pmid30619549, year = {2018}, author = {Rennstam Rubbmark, O and Sint, D and Horngacher, N and Traugott, M}, title = {A broadly applicable COI primer pair and an efficient single-tube amplicon library preparation protocol for metabarcoding.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12335-12350}, doi = {10.1002/ece3.4520}, pmid = {30619549}, issn = {2045-7758}, abstract = {The nucleotide variation in the cytochrome c oxidase subunit I (COI) gene makes it ideal for assigning sequences to species. However, this variability also makes it difficult to design truly universal primers. Here, we present the forward primer "Sauron-S878," specifically designed to facilitate library preparation for metabarcoding. This primer is modified to improve the coverage of terrestrial species compared to the primer mCOIintF, optimized for aquatic systems, which raised the in silico coverage from 74.4% to 98.3% of available NCBI sequences (perfect match in 3' region, up to three mismatches in remaining primer). When paired with the reverse primer "jgHCO2198" (fragment length ~313 bp), these primers amplified 98.4% of 255 tested DNA extracts from various taxa, which are better than many other common COI barcoding primers. Furthermore, a single-tube protocol was developed, wherein these primers amplify the target gene, and attach MIDs and Illumina sequencing adapters in one reaction. This eliminates the need for re-amplification or enzymatic ligation during library preparation while keeping the flexibility to modularly combine primers and MIDs. Using the single-tube approach, three replicates of three mock samples were sequenced on a MiSeq platform with no adverse effects compared to commercial Nextera indexing kits. From this run, 75% of all included taxa could be recovered, with no considerable bias among taxonomic groups. Despite the fact that 98.4% of the extracts were confirmed to amplify in vitro, this number was lower than expected. A reason for this discrepancy was a clear link between the relative concentration of a specific DNA type in the template and the number of returned reads for this DNA. We would argue that such a bias may be especially problematic in metabarcoding where samples usually contain trace DNA in unknown amounts. However, how this affects the completeness of metabarcoding results has yet been poorly investigated.}, } @article {pmid30619548, year = {2018}, author = {Rush, GP and Clarke, LE and Stone, M and Wood, MJ}, title = {Can drones count gulls? Minimal disturbance and semiautomated image processing with an unmanned aerial vehicle for colony-nesting seabirds.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12322-12334}, doi = {10.1002/ece3.4495}, pmid = {30619548}, issn = {2045-7758}, abstract = {Accurate counts of wild populations are essential to monitor change through time, but some techniques demand specialist surveyors and may result in unacceptable disturbance or inaccurate counts. Recent technological developments in unmanned aerial vehicles (UAVs) offer great potential for a range of survey and monitoring approaches. They literally offer a bird's-eye view, but this increased power of observation presents the challenge of translating large amounts of imagery into accurate survey data. Seabirds, in particular, present the particular challenges of nesting in large, often inaccessible colonies that are difficult to view for ground observers, which are commonly susceptible to disturbance. We develop a protocol for carrying out UAV surveys of a breeding seabird colony (Lesser Black-backed Gulls, Larus fuscus) and subsequent image processing to provide a semiautomated classification for counting the number of birds. Behavioral analysis of the gull colonies demonstrated that minimal disturbance occurred during UAV survey flights at an altitude of 15 m above ground level, which provided high-resolution imagery for analysis. A protocol of best practice was developed using the expertise from both a UAV perspective and that of a dedicated observer. A GIS-based semiautomated classification process successfully counted the gulls, with a mean agreement of 98% and a correlation of 99% with manual counts of imagery. We also propose a method to differentiate between the different gull species captured by our survey. Our UAV survey and analysis approach provide accurate counts (when comparing manual vs. semi-automated counts taken from the UAV imagery) of a wild seabird population with minimal disturbance, with the potential to expand this to include species differentiation. The continued development of analytical and survey tools whilst minimizing the disturbance to wild populations is both key to unlocking the future of the rapid advances in UAV technology for ecological survey.}, } @article {pmid30619547, year = {2018}, author = {Correia, HE}, title = {Spatiotemporally explicit model averaging for forecasting of Alaskan groundfish catch.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12308-12321}, doi = {10.1002/ece3.4488}, pmid = {30619547}, issn = {2045-7758}, abstract = {Fisheries management is dominated by the need to forecast catch and abundance of commercially and ecologically important species. The influence of spatial information and environmental factors on forecasting error is not often considered. I propose a forecasting method called spatiotemporally explicit model averaging (STEMA) to combine spatial and temporal information through model averaging. I examine the performance of STEMA against two popular forecasting models and a modern spatial prediction model: the autoregressive integrated moving averages with explanatory variables (ARIMAX) model, the Bayesian hierarchical model, and the varying coefficient model. I focus on applying the methods to four species of Alaskan groundfish for which catch data are available. My method reduces forecasting errors significantly for most of the tested models when compared to ARIMAX, Bayesian, and varying coefficient methods. I also consider the effect of sea surface temperature (SST) on the forecasting of catch, as multiple studies reveal a potential influence of water temperature on the survival and growth of juvenile groundfish. For most of the preferred models, inclusion of SST in the model improved forecasting of catch. It is advisable to consider both spatial information and relevant environmental factors in forecasting models to obtain more accurate projections of population abundance. The STEMA method is capable of accounting for spatial information in forecasting and can be applied to various types of data because of its flexible varying coefficient model structure. It is therefore a suitable forecasting method for application to many fields including ecology, epidemiology, and climatology.}, } @article {pmid30619546, year = {2018}, author = {Bonnaffé, W and Martin, M and Mugabo, M and Meylan, S and Le Galliard, JF}, title = {Ontogenetic trajectories of body coloration reveal its function as a multicomponent nonsenescent signal.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12299-12307}, doi = {10.1002/ece3.4369}, pmid = {30619546}, issn = {2045-7758}, abstract = {The understanding of developmental patterns of body coloration is challenging because of the multicomponent nature of color signals and the multiple selective pressures acting upon them, which further depend on the sex of the bearer and area of display. Pigmentary colors are thought to be strongly involved in sexual selection, while structural colors are thought to generally associate with conspecifics interactions and improve the discrimination of pigmentary colors. Yet, it remains unclear whether age dependency in each color component is consistent with their potential function. Here, we address lifelong ontogenetic variation in three color components (i.e. UV, pigmentary, and skin background colors) in a birth cohort of common lizards Zootoca vivipara across three ventral body regions (i.e. throat, chest, and belly). All three color components developed sexual dichromatism, with males displaying stronger pigmentary and UV colors but weaker skin background coloration than females. The development of color components led to a stronger sexual dichromatism on the concealed ventral region than on the throat. No consistent signs of late-life decay in color components were found except for a deceleration of UV reflectance increase with age on the throat of males. These results suggest that body color components in common lizards are primarily nonsenescent sexual signals, but that the balance between natural and sexual selection may be altered by the conspicuousness of the area of display. These results further support the view that skin coloration is a composite trait constituted of multiple color components conveying multiple signals depending on age, sex, and body location.}, } @article {pmid30619545, year = {2018}, author = {Alessi, AM and Redeker, KR and Chong, JPJ}, title = {A practical introduction to microbial molecular ecology through the use of isolation chips.}, journal = {Ecology and evolution}, volume = {8}, number = {24}, pages = {12286-12298}, doi = {10.1002/ece3.4748}, pmid = {30619545}, issn = {2045-7758}, abstract = {In the context of antimicrobial resistance as one of the most serious issues faced globally by health providers, we explored a practical introduction to molecular microbial ecology. We designed field work and practical experiments for third year members of a 4 year undergraduate Masters Program, in which the students employed traditional and novel isolation techniques to identify antimicrobial activities from soil dwelling microorganisms. Students gained experience in isolating DNA from complex microbial communities, amplifying 16S rRNA genes and applied richness/diversity indices as well as principal coordinate analyses to the interpretation of the data they obtained from high throughput sequencing. Our results confirmed that isolation chips facilitate the growth of a greater diversity and different species subset from the complex soil microorganism community than traditional plate spreading techniques. However, rarefaction of 16S rRNA amplicon sequencing data showed that the majority of observed species in soil remain unculturable by current methods. Based on the written reports produced by the students carrying out the work, we concluded that the described protocols are robust and informative, that these activities provide a good practical introduction to the theories and practice of molecular ecology and can be easily deployed to groups of six or more students in a cost-effective manner.}, } @article {pmid30606460, year = {2018}, author = {Ruiz-Orera, J and Albà, MM}, title = {Translation of Small Open Reading Frames: Roles in Regulation and Evolutionary Innovation.}, journal = {Trends in genetics : TIG}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tig.2018.12.003}, pmid = {30606460}, issn = {0168-9525}, abstract = {The translatome can be defined as the sum of the RNA sequences that are translated into proteins in the cell by the ribosomal machinery. Until recently, it was generally assumed that the translatome was essentially restricted to evolutionary conserved proteins encoded by the set of annotated protein-coding genes. However, it has become increasingly clear that it also includes small regulatory open reading frames (ORFs), functional micropeptides, de novo proteins, and the pervasive translation of likely nonfunctional proteins. Many of these ORFs have been discovered thanks to the development of ribosome profiling, a technique to sequence ribosome-protected RNA fragments. To fully capture the diversity of translated ORFs, we propose a comprehensive classification that includes the new types of translated ORFs in addition to standard proteins.}, } @article {pmid30605626, year = {2018}, author = {Zhong, C and Fu, Y and Pan, W and Yu, J and Wang, J}, title = {Atoh1 and other related key regulators in the development of auditory sensory epithelium in the mammalian inner ear: function and interplay.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.025}, pmid = {30605626}, issn = {1095-564X}, abstract = {Damage or loss of auditory hair cells leads to irreversible sensorineural hearing loss in human, thus regeneration of these cells to reconstruct auditory sensory epithelium holds the promise for the treatment of deafness. Regulatory factors involved in the development of auditory sensory epithelium play crucial roles in hair cell regeneration and hearing restoration. Here, we first focus on the transcription factor Atoh1 which is critical for hair cell development and regeneration, and comprehensively summarize the current understanding of the protein structure, target binding motif, developmental expression pattern, functional role, and upstream and downstream regulatory mechanism of Atoh1 in the context of controlling the cell fate commitment to hair cells or transdifferentiation from supporting cells. We also discuss cellular context dependency of Atoh1 in hair cell induction which should be taken into consideration when using Atoh1 gene therapy for hair cell regeneration. Next, we review the roles of Gfi1, Pou4f3, and Barhl1 in hair cell maturation and maintenance, and suggest that manipulation of these genes and their downstream targets will be helpful for the generation of functional hair cells with long-term viability. Finally, we provide an overview of the interplay between Notch, Wnt, Shh, and FGF signaling pathways during auditory sensory epithelium development. By analyzing crosstalk between these pathways, we suggest that combination of Wnt signaling activation with Hey1 and Hey2 inhibition will be crucial for hair cell regeneration and hearing restoration. Furthermore, this review highlights the importance of deeper understanding of the cellular context for hair cell development and the interconnection between these key regulators in developing new strategies to treat sensorineural hearing loss.}, } @article {pmid30604833, year = {2018}, author = {Antinori, A and Di Biagio, A and Marcotullio, S and Sarmati, L and Andreoni, M and Angarano, G and Chirianni, A and d'Arminio Monforte, A and Di Perri, G and Galli, M and Gianotti, N and Girardi, E and Gori, A and Mussini, C and Perno, CF and Lazzarin, A}, title = {Evidence-based renewal of the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {247-255}, pmid = {30604833}, issn = {1121-7138}, abstract = {The Italian Society for Infectious and Tropical Diseases (SIMIT) in collaboration with the Technical Health Committee (Sections L and M) of the Italian Ministry of Health have supported the renewal of the recommendations for the Italian guidelines for the use of antiretroviral agents and the diagnostic-clinical management of HIV-1 infected persons. This publication summarizes the latest updates to the 2017 version of the Italian Guidelines for the management of HIV-1 infected patients and the use of antiretroviral drugs. New recommendations were released framing the clinical questions the use of antiretrovirals according to the Patient Intervention Comparator Outcome (PICO) methodology and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. Diagnostic tools for immunological and virological monitoring, when to start, what to start, optimization and therapeutic failure were updated in order to include the recommendation obtained with these newly developed methods. For a complete review of clinical and therapeutic relevant topics we refer the reader to the extended version of the Guidelines.}, } @article {pmid30600140, year = {2018}, author = {Weiner, A and Enninga, J}, title = {The Pathogen-Host Interface in Three Dimensions: Correlative FIB/SEM Applications.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.11.011}, pmid = {30600140}, issn = {1878-4380}, abstract = {Pathogens survive and propagate within host cells through a wide array of complex interactions. Tracking the molecular and cellular events by multidimensional fluorescence microscopy has been a widespread tool for research on intracellular pathogens. Through major advancements in 3D electron microscopy, intracellular pathogens can also be visualized in their cellular environment to an unprecedented level of detail within large volumes. Recently, multidimensional fluorescence microscopy has been correlated with volume electron microscopy, combining molecular and functional information with the overall ultrastructure of infection events. In this review, we provide a short introduction to correlative focused ion beam/scanning electron microscopy (c-FIB/SEM) tomography and illustrate its utility for intracellular pathogen research through a series of studies on Shigella, Salmonella, and Brucella cellular invasion. We conclude by discussing current limitations of and prospects for this approach.}, } @article {pmid30600139, year = {2019}, author = {Spinler, JK and Karri, V and Hirschi, KD}, title = {Planting the Microbiome.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {90-93}, doi = {10.1016/j.tim.2018.12.001}, pmid = {30600139}, issn = {1878-4380}, abstract = {Plant-derived microRNAs stabilized by species-specific lipid nanoparticles mediate interkingdom communication through bacterial intermediates and impact consumer health. Ingested by distinct gut bacteria, these microRNA-containing particles alter bacterial gene expression to affect host immunity. This three-kingdom interplay provides compelling approaches for health-directed dietary interventions for consumers.}, } @article {pmid30599197, year = {2018}, author = {Zhou, H and Visnovska, T and Gong, H and Schmeier, S and Hickford, J and Ganley, ARD}, title = {Contrasting patterns of coding and flanking region evolution in mammalian keratin associated protein-1 genes.}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ympev.2018.12.031}, pmid = {30599197}, issn = {1095-9513}, abstract = {Mammalian genomes contain a number of duplicated genes, and sequence identity between these duplicates can be maintained by purifying selection. However, between-duplicate recombination can also maintain sequence identity between copies, resulting in a pattern known as concerted evolution where within-genome repeats are more similar to each other than to orthologous repeats in related species. Here we investigated the tandemly-repeated keratin-associated protein 1 (KAP1) gene family, KRTAP1, which encodes proteins that are important components of hair and wool in mammals. Comparison of eutherian mammal KRTAP1 gene repeats within and between species shows a strong pattern of concerted evolution. However, in striking contrast to the coding regions of these genes, we find that the flanking regions have a divergent pattern of evolution. This contrast in evolutionary pattern transitions abruptly near the start and stop codons of the KRTAP1 genes. We reveal that this difference in evolutionary patterns is not explained by conventional purifying selection, nor is it likely a consequence of codon adaptation or reverse transcription of KRTAP1-n mRNA. Instead, the evidence suggests that these contrasting patterns result from short-tract gene conversion events that are biased to the KRTAP1 coding region by selection and/or differential sequence divergence. This work demonstrates the power that gene conversion has to finely shape the evolution of repetitive genes, and provides another distinctive pattern of contrasting evolutionary outcomes that results from gene conversion. A greater emphasis on exploring the evolution of multi-gene eukaryotic families will reveal how common different contrasting evolutionary patterns are in gene duplicates.}, } @article {pmid30599151, year = {2018}, author = {Hu, S and Skelly, LE and Kaymak, E and Freeberg, L and Lo, TW and Kuersten, S and Ryder, SP and Haag, ES}, title = {Multi-modal regulation of C. elegans hermaphrodite spermatogenesis by the GLD-1-FOG-2 complex.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.11.024}, pmid = {30599151}, issn = {1095-564X}, abstract = {Proper germ cell sex determination in Caenorhabditis nematodes requires a network of RNA-binding proteins (RBPs) and their target mRNAs. In some species, changes in this network enabled limited XX spermatogenesis, and thus self-fertility. In C. elegans, one of these selfing species, the global sex-determining gene tra-2 is regulated in germ cells by a conserved RBP, GLD-1, via the 3' untranslated region (3'UTR) of its transcript. A C. elegans-specific GLD-1 cofactor, FOG-2, is also required for hermaphrodite sperm fate, but how it modifies GLD-1 function is unknown. Germline feminization in gld-1 and fog-2 null mutants has been interpreted as due to cell-autonomous elevation of TRA-2 translation. Consistent with the proposed role of FOG-2 in translational control, the abundance of nearly all GLD-1 target mRNAs (including tra-2) is unchanged in fog-2 mutants. Epitope tagging reveals abundant TRA-2 expression in somatic tissues, but an undetectably low level in wild-type germ cells. Loss of gld-1 function elevates germline TRA-2 expression to detectable levels, but loss of fog-2 function does not. A simple quantitative model of tra-2 activity constrained by these results can successfully sort genotypes into normal or feminized groups. Surprisingly, fog-2 and gld-1 activity enable the sperm fate even when GLD-1 cannot bind to the tra-2 3' UTR. This suggests the GLD-1-FOG-2 complex regulates uncharacterized sites within tra-2, or other mRNA targets. Finally, we quantify the RNA-binding capacities of dominant missense alleles of GLD-1 that act genetically as "hyper-repressors" of tra-2 activity. These variants bind RNA more weakly in vitro than does wild-type GLD-1. These results indicate that gld-1 and fog-2 regulate germline sex via multiple interactions, and that our understanding of the control and evolution of germ cell sex determination in the C. elegans hermaphrodite is far from complete.}, } @article {pmid30598817, year = {2018}, author = {Gantchoff, M and Wang, G and Beyer, D and Belant, J}, title = {Scale-dependent home range optimality for a solitary omnivore.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12271-12282}, doi = {10.1002/ece3.4690}, pmid = {30598817}, issn = {2045-7758}, abstract = {Spatial and temporal heterogeneity are fundamental mechanisms structuring home ranges. Under optimality, an individual should structure their space use economically to maximize fitness. We evaluated support for three hypotheses related to range optimality in American black bears (Ursus americanus), predicting (a) range location on a landscape will correspond with high vegetation productivity, (b) increasing forest fragmentation will result in larger ranges, and (c) increasing proportion of forest and/or mean vegetation productivity will result in smaller ranges. We used black bear radio telemetry data from Michigan (2009-2015), Missouri (2010-2016), and Mississippi (2008-2017), USA. Annual space use excluded winter, and we separated seasonal space use into spring, summer, and fall. We collected data from 143 bears (80 females, 63 males), resulting in 97 annual and 538 seasonal ranges. We used generalized linear mixed models to evaluate productivity (estimated through Normalized Difference Vegetation Index [NDVI]) selection, and range size (km2) variation between individuals. At the annual scale, black bears consistently selected areas with greater vegetation productivity than the surrounding landscape; yet selection weakened and was more variable seasonally. Opposite to our prediction, we found that increasing fragmentation consistently resulted in smaller ranges; non-forested land covers and forest edges might provide greater abundance or more diverse foods for bears. Ranges with a greater proportion of forest were smaller, likely reflecting an increase in food and cover which could reduce movements, yet there was no support for more productive ranges also being smaller as expected from an area minimizing strategy. Black bears displayed a scale-dependent space use strategy: at larger spatial and temporal scales, productivity acted as the strongest limiting factor and energy maximizing was the dominant strategy, while an area minimizing strategy was exhibited seasonally. We revealed consistent, scale-dependent responses by black bears to environmental conditions, demonstrating the intrinsic plasticity of this adaptable omnivore.}, } @article {pmid30598816, year = {2018}, author = {Auld, JR}, title = {The effects of diet and mating system on reproductive (and post-reproductive) life span in a freshwater snail.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12260-12270}, doi = {10.1002/ece3.4689}, pmid = {30598816}, issn = {2045-7758}, abstract = {The length of the reproductive life span, along with the number/frequency/magnitude of reproductive events, quantifies an individual's potential contribution to the next generation. By examining reproductive life span, and distinguishing it from somatic life span, we gain insight into critical aspects of an individual's potential fitness as well as reproductive and somatic senescence. Additionally, differentiating somatic and reproductive life spans can provide insight into the existence of a post-reproductive period and factors that shape its duration. Given the known importance of diet and mating system on resource allocation, I reared individual freshwater snails (Physa acuta) from 22 full-sib families under a 2 × 2 factorial design that crossed mate availability (available [outcrossing] or not [selfing]) and diet (Spirulina or lettuce) and quantified aspects of the entire life history enabling me to distinguish reproductive and somatic life spans, determine the total number of reproductive events, and evaluate how the reproductive rate changes with age. Overall, mated snails experienced shorter reproductive and somatic life spans; a diet of Spirulina also shortened both reproductive and somatic life spans. A post-reproductive period existed in all conditions; its duration was proportional to somatic but not reproductive life span. I evaluate several hypotheses for the existence and duration of the post-reproductive period, including a novel hypothesis that the post-reproductive period may result from an increase in reproductive interval with age. I conclude that the post-reproductive period may be indicative of a randomly timed death occurring as the interval between reproductive events continues to increase. As such, a "post-reproductive" period can be viewed as a by-product of a situation where reproductive senescence outpaces somatic senescence.}, } @article {pmid30598815, year = {2018}, author = {Muola, A and Stenberg, JA}, title = {Folivory has long-term effects on sexual but not on asexual reproduction in woodland strawberry.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12250-12259}, doi = {10.1002/ece3.4687}, pmid = {30598815}, issn = {2045-7758}, abstract = {Plant fitness is often a result of both sexual and asexual reproductive success and, in perennial plants, over several years. Folivory can affect both modes of reproduction. However, little is known about the effects of folivory on resource allocation to the two modes of reproduction simultaneously and across years. In a 2-year common garden experiment, we examined the effects of different levels of folivory by the strawberry leaf beetle, Galerucella tenella, on current growth, as well as current and future sexual and asexual reproduction (runners) of perennial woodland strawberry, Fragaria vesca. In addition, we measured the chlorophyll content in leaves in the year of experimental damage to determine whether there was increased photosynthetic activity, and, thus, a compensatory response to herbivory. Finally, we tested whether the previous year's folivory, as a result of its effect on plant fitness, affected the level of natural herbivory the plant experienced during the subsequent year. In the year of experimental damage, plants that were exposed to moderate and high levels of folivory (25% and 50% leaf area consumed, respectively) increased their photosynthetic activity compared to control plants. However, only plants exposed to high folivory exhibited negative effects, with a lower probability of flowering compared to control plants, indicating that plants exposed to low or moderate folivory were able to compensate for the damage. Negative effects of folivory were carried over to the subsequent year. Plants that were exposed to moderate folivory (25% leaf area consumed) during first year produced fewer flowers and fruits in the subsequent year. Runner production was consistently unaffected by folivory. The effects of experimental folivory on the level of natural herbivory were mediated via its effects on plant fitness. Our results show that the negative effects of folivory only influence sexual reproduction in woodland strawberry. Furthermore, even though woodland strawberry can tolerate moderate amounts of folivory in the short term, the negative effects on fitness appear later; this highlights the importance of studying the effects of herbivory over consecutive years in perennial plants.}, } @article {pmid30598814, year = {2018}, author = {de Souza, AC and Portela, RCQ and de Mattos, EA}, title = {Demographic processes limit upward altitudinal range expansion in a threatened tropical palm.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12238-12249}, doi = {10.1002/ece3.4686}, pmid = {30598814}, issn = {2045-7758}, abstract = {Understanding the factors that determine species' range limits is a key issue in ecology, and is fundamental for biodiversity conservation under widespread global environmental change. Elucidating how altitudinal variation affects demographic processes may provide important clues for understanding the factors limiting current and future species distributions, yet population dynamics at range limits are still poorly understood. Here, we tested the hypothesis that lower abundance at a species' upper altitudinal range limit is related to lower vital rates. We compared the dynamics of two populations of the tropical palm Euterpe edulis, located near and at the edge of its altitudinal limit of distribution in the Brazilian Atlantic Forest. Data from four annual censuses, from 2012 to 2015, were used. We used matrix population models to estimate asymptotic population growth rates and the elasticity values for the vital rates of the two populations of E. edulis. Life table response experiments were used to compare population performance by measuring the contribution of each vital rate to population growth rates. Population growth rates were not significantly different from one in either population, indicating that both populations were stable during the study period. However, the abundance of all ontogenetic stages was lower at the altitudinal range limit, which was related to decreases in some vital rates, especially fecundity. Additionally, there were higher elasticity values for the survival of immatures and reproductive individuals, compared to all other vital rates, in both populations. Synthesis. Our results show that even a small-scale environmental variation near range limits is sufficient to drive changes in the demography of this threatened palm. A minor increase in elevation approaching the limit of altitudinal distribution may reduce environmental suitability and affect population vital rates, thus contributing to setting upper altitudinal range limits for plants.}, } @article {pmid30598813, year = {2018}, author = {Singh, SP and Groeneveld, JC and Hart-Davis, MG and Backeberg, BC and Willows-Munro, S}, title = {Seascape genetics of the spiny lobster Panulirus homarus in the Western Indian Ocean: Understanding how oceanographic features shape the genetic structure of species with high larval dispersal potential.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12221-12237}, doi = {10.1002/ece3.4684}, pmid = {30598813}, issn = {2045-7758}, abstract = {This study examines the fine-scale population genetic structure and phylogeography of the spiny lobster Panulirus homarus in the Western Indian Ocean. A seascape genetics approach was used to relate the observed genetic structure based on 21 microsatellite loci to ocean circulation patterns, and to determine the influence of latitude, sea surface temperature (SST), and ocean turbidity (KD490) on population-level processes. At a geospatial level, the genetic clusters recovered corresponded to three putative subspecies, P. h. rubellus from the SW Indian Ocean, P. h. megasculptus from the NW Indian Ocean, and P. h. homarus from the tropical region in-between. Virtual passive Lagrangian particles advected using satellite-derived ocean surface currents were used to simulate larval dispersal. In the SW Indian Ocean, the dispersion of particles tracked over a 4-month period provided insight into a steep genetic gradient observed at the Delagoa Bight, which separates P. h. rubellus and P. h. homarus. South of the contact zone, particles were advected southwestwards by prevailing boundary currents or were retained in nearshore eddies close to release locations. Some particles released in southeast Madagascar dispersed across the Mozambique Channel and reached the African shelf. Dispersal was characterized by high seasonal and inter-annual variability, and a large proportion of particles were dispersed far offshore and presumably lost. In the NW Indian Ocean, particles were retained within the Arabian Sea. Larval retention and self-recruitment in the Arabian Sea could explain the recent genetic divergence between P. h. megasculptus and P. h. homarus. Geographic distance and minimum SST were significantly associated with genetic differentiation in multivariate analysis, suggesting that larval tolerance to SST plays a role in shaping the population structure of P. homarus.}, } @article {pmid30598812, year = {2018}, author = {Larrue, S and Butaud, JF and Daehler, CC and Ballet, S and Chadeyron, J and Oyono, R}, title = {Persistence at the final stage of volcanic island ontogeny: Abiotic predictors explain native plant species richness on 111 remote Pacific atolls.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12208-12220}, doi = {10.1002/ece3.4680}, pmid = {30598812}, issn = {2045-7758}, abstract = {Aim: The final island ontogeny of the general dynamic model (GDM) (i.e., before island submergence) in tropical oceans corresponds to the coral atoll stage. Here, we examined whether the species richness of native vascular plants (indigenous and endemic species) on atolls is controlled by spatial and/or physical processes. We also predicted that atolls strongly affected by anthropogenic disturbance would have lower native species richness than predicted by spatial and physical processes.

Location: Marshall Islands, Kiribati Islands, Nauru, Niue, Johnston, Cook Islands, French Polynesia and Pitcairn Islands (Pacific Ocean).

Taxon: Native vascular plants.

Methods: We used stepwise regression to test the relative influence of five biogeographic variables on native species richness. Relationships were assessed for the full set of 111 Pacific coral atolls, as well as for atoll subsets ranging from 9 to 45 atolls. An index of human impact was then estimated, and residuals in the regression model predicting species richness from biogeographic variables were compared with the level of human impact.

Results: A regression model including atoll area, highest atoll elevation, the stepping stone distances from the nearest raised atoll and volcanic island explained native species richness on the 111 Pacific coral atolls. Regression models for different archipelagos and atoll subsets were also significant. Endemic species richness was significantly linked with highest atoll elevation and the stepping stone distances from the nearest raised atoll. Residuals in the biogeographic regression model were barely related to human impact across the 111 atolls but were significantly related to human impact in the Kiribati atolls.

Main conclusions: Native species richness on atolls is mainly controlled by physical and spatial characteristics. However, anthropogenic disturbances have altered the predicted pattern of native species richness leading to a lower model fit in some atoll subsets.}, } @article {pmid30598811, year = {2018}, author = {Rodriguez-Casariego, JA and Ladd, MC and Shantz, AA and Lopes, C and Cheema, MS and Kim, B and Roberts, SB and Fourqurean, JW and Ausio, J and Burkepile, DE and Eirin-Lopez, JM}, title = {Coral epigenetic responses to nutrient stress: Histone H2A.X phosphorylation dynamics and DNA methylation in the staghorn coral Acropora cervicornis.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12193-12207}, doi = {10.1002/ece3.4678}, pmid = {30598811}, issn = {2045-7758}, abstract = {Nutrient pollution and thermal stress constitute two of the main drivers of global change in the coastal oceans. While different studies have addressed the physiological effects and ecological consequences of these stressors in corals, the role of acquired modifications in the coral epigenome during acclimatory and adaptive responses remains unknown. The present work aims to address that gap by monitoring two types of epigenetic mechanisms, namely histone modifications and DNA methylation, during a 7-week-long experiment in which staghorn coral fragments (Acropora cervicornis) were exposed to nutrient stress (nitrogen, nitrogen + phosphorus) in the presence of thermal stress. The major conclusion of this experiment can be summarized by two main results: First, coral holobiont responses to the combined effects of nutrient enrichment and thermal stress involve the post-translational phosphorylation of the histone variant H2A.X (involved in responses to DNA damage), as well as nonsignificant modifications in DNA methylation trends. Second, the reduction in H2A.X phosphorylation (and the subsequent potential impairment of DNA repair mechanisms) observed after prolonged coral exposure to nitrogen enrichment and thermal stress is consistent with the symbiont-driven phosphorus limitation previously observed in corals subject to nitrogen enrichment. The alteration of this epigenetic mechanism could help to explain the synergistic effects of nutrient imbalance and thermal stress on coral fitness (i.e., increased bleaching and mortality) while supporting the positive effect of phosphorus addition to improving coral resilience to thermal stress. Overall, this work provides new insights into the role of epigenetic mechanisms during coral responses to global change, discussing future research directions and the potential benefits for improving restoration, management and conservation of coral reef ecosystems worldwide.}, } @article {pmid30598810, year = {2018}, author = {Jones, W and Kulma, K and Bensch, S and Cichoń, M and Kerimov, A and Krist, M and Laaksonen, T and Moreno, J and Munclinger, P and Slater, FM and Szöllősi, E and Visser, ME and Qvarnström, A}, title = {Interspecific transfer of parasites following a range-shift in Ficedula flycatchers.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12183-12192}, doi = {10.1002/ece3.4677}, pmid = {30598810}, issn = {2045-7758}, abstract = {Human-induced climate change is expected to cause major biotic changes in species distributions and thereby including escalation of novel host-parasite associations. Closely related host species that come into secondary contact are especially likely to exchange parasites and pathogens. Both the Enemy Release Hypothesis (where invading hosts escape their original parasites) and the Novel Weapon Hypothesis (where invading hosts bring new parasites that have detrimental effects on native hosts) predict that the local host will be most likely to experience a disadvantage. However, few studies evaluate the occurrence of interspecific parasite transfer by performing wide-scale geographic sampling of pathogen lineages, both within and far from host contact zones. In this study, we investigate how haemosporidian (avian malaria) prevalence and lineage diversity vary in two, closely related species of passerine birds; the pied flycatcher Ficedula hypoleuca and the collared flycatcher F. albicollis in both allopatry and sympatry. We find that host species is generally a better predictor of parasite diversity than location, but both prevalence and diversity of parasites vary widely among populations of the same bird species. We also find a limited and unidirectional transfer of parasites from pied flycatchers to collared flycatchers in a recent contact zone. This study therefore rejects both the Enemy Release Hypothesis and the Novel Weapon Hypothesis and highlights the complexity and importance of studying host-parasite relationships in an era of global climate change and species range shifts.}, } @article {pmid30598809, year = {2018}, author = {Fukui, S and May-McNally, SL and Taylor, EB and Koizumi, I}, title = {Maladaptive secondary sexual characteristics reduce the reproductive success of hybrids between native and non-native salmonids.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12173-12182}, doi = {10.1002/ece3.4676}, pmid = {30598809}, issn = {2045-7758}, abstract = {Human-mediated hybridization between introduced and native species is one of the most serious threats to native taxa. Although field studies have attempted to quantify the relative fitness or reproductive success of parental species and their hybrids, only a few studies have unraveled the factors determining the fitness of hybrids. Here, we hypothesized that maladaptive secondary sexual characteristics may reduce fitness of hybrids between two fish species. To test this, we evaluated the reproductive success of introduced brook trout (BT: Salvelinus fontinalis), native white-spotted charr (WSC: S. leucomaenis) and their hybrids in a natural stream in Hokkaido, Japan, where the two parental species show remarkably different male secondary sexual characteristics, such as elongated jaws and deeper bodies. We predicted that introgression from WSC is maladaptive for BT males because the BT male has more prominent secondary sexual characteristics. Our results suggest that both sexual selection and outbreeding depression in males and females significantly influence an individual's reproductive success. Our results also suggest that asymmetric introgression may increase the risks to persistence in the recipient species.}, } @article {pmid30598808, year = {2018}, author = {Song, X and Zeng, X and Tian, D}, title = {Allocation of forest net primary production varies by forest age and air temperature.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12163-12172}, doi = {10.1002/ece3.4675}, pmid = {30598808}, issn = {2045-7758}, abstract = {Carbon partition among plant parts has a vital influence not only on the growth of individual plants but also on decomposition, carbon and nitrogen sequestration, and plant-atmosphere water exchange. Although many studies have tried to reveal plant growth mechanisms using observational living biomass or the biomass ratio among different organs, knowledge and understanding about carbon partition is still scarce and exists much uncertainty. In this work, a dataset about 1,089 sample plots of natural forests downloaded from the Chinese Ecosystem Research Network (CERN) was used to explore the dependences of net primary production (NPP) partition among foliage, stem and branch, and root on forest age, and mean annual temperature (MAT). The results found that (a) for all forest types, NPP partition had a significant relationship with forest age (p < 0.0001), that is, younger plants usually allocated a higher proportion of the NPP to stems, branches, and roots. As plants aged, an increasing proportion of the NPP was allocated to foliage; (b) MAT was negatively correlated with the proportions of the NPP allocated to foliage (Fleaf; %) and roots (Froot; %), while proportions of the NPP allocated to stems and branches (Fstbr; %) were positively dependent on MAT; (c) independent effect analysis demonstrated that forest age had a larger direct influence on Fleaf and Froot, while MAT was relatively important for Fstbr; and (d) forest age and MAT had a stronger combined effect on NPP allocation for broad-leaved forests, while for needled-leaved forests, the influences of forest age and MAT existed large differences among different forest types. This work not only is important for understanding the contribution of climatic factor and forest age on forest NPP partition, but also provides valuable ideas for developing ecological models.}, } @article {pmid30598807, year = {2018}, author = {Westphal, MF and Noble, T and Butterfield, HS and Lortie, CJ}, title = {A test of desert shrub facilitation via radiotelemetric monitoring of a diurnal lizard.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12153-12162}, doi = {10.1002/ece3.4673}, pmid = {30598807}, issn = {2045-7758}, abstract = {Preservation of desert ecosystems is a worldwide conservation priority. Shrubs can play a key role in the structure of desert communities and can function as foundation species. Understanding desert shrub ecology is therefore an important task in desert conservation. A useful model for the function of shrubs in deserts is ecological facilitation, which explores benefits that shrubs confer on their community. Facilitation has been well developed in the context of shrub-plant interactions but less well studied for plant-animal interactions. We used radiotelemetry to test the hypothesis that a dominant desert shrub facilitates one species of diurnal lizard. We hypothesized that the blunt-nosed leopard lizard Gambelia sila would spend some part of its daily activity cycle associated with California jointfir Ephedra californica, and that lizard association with shrubs would increase during the afternoon peak temperature period. We relocated lizards three times daily for 24 days and scored whether lizards were within 0.5 m of a shrub, which we used as an indicator of shrub association. For each relocation, we also scored lizard association with a set of predefined microhabitat features. We also scored lizard behavior according to a set of predefined behavioral traits. We constructed home ranges following the minimum convex polygon method and generated estimates of shrub density and relative shrub area within each home range polygon. We obtained 1,190 datapoints from a sample of 27 lizards. We found that lizards were associated with open sites significantly more often than with shrubs but were associated with shrubs more than predicted by percent shrub area within their home ranges. Lizards were associated significantly more often under shrubs during the afternoon peak temperature period, and lizards were observed cooling under shrubs significantly more often. The frequency of association of individual lizards with shrubs was not correlated with the density of shrubs within their home range. Synthesis and Applications. Shrubs can be considered as a component of high-quality habitat for ectothermic desert vertebrates for the purposes of restoration and management. Furthermore, radiotelemetry provides a novel methodological approach for assessing shrub-animal facilitative interactions within desert communities.}, } @article {pmid30598806, year = {2018}, author = {Fairweather, R and Bradbury, IR and Helyar, SJ and de Bruyn, M and Therkildsen, NO and Bentzen, P and Hemmer-Hansen, J and Carvalho, GR}, title = {Range-wide genomic data synthesis reveals transatlantic vicariance and secondary contact in Atlantic cod.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12140-12152}, doi = {10.1002/ece3.4672}, pmid = {30598806}, issn = {2045-7758}, abstract = {Recent advances in genetic and genomic analysis have greatly improved our understanding of spatial population structure in marine species. However, studies addressing phylogeographic patterns at oceanic spatial scales remain rare. In Atlantic cod (Gadus morhua), existing range-wide examinations suggest significant transatlantic divergence, although the fine-scale contemporary distribution of populations and potential for secondary contact are largely unresolved. Here, we explore transatlantic phylogeography in Atlantic cod using a data-synthesis approach, integrating multiple genome-wide single-nucleotide polymorphism (SNP) datasets representative of different regions to create a single range-wide dataset containing 1,494 individuals from 54 locations and genotyped at 796 common loci. Our analysis highlights significant transatlantic divergence and supports the hypothesis of westward post-glacial colonization of Greenland from the East Atlantic. Accordingly, our analysis suggests the presence of transatlantic secondary contact off eastern North America and supports existing perspectives on the phylogeographic history of Atlantic cod with an unprecedented combination of genetic and geographic resolution. Moreover, we demonstrate the utility of integrating distinct SNP databases of high comparability.}, } @article {pmid30598805, year = {2018}, author = {Zhang, R and Schellenberg, MP and Han, G and Wang, H and Li, J}, title = {Drought weakens the positive effects of defoliation on native rhizomatous grasses but enhances the drought-tolerance traits of native caespitose grasses.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12126-12139}, doi = {10.1002/ece3.4671}, pmid = {30598805}, issn = {2045-7758}, abstract = {The objective of this study was to evaluate the drought tolerance, compensatory growth, and different plant traits between two native perennial caespitose grasses and two native rhizomatous grasses in response to drought and defoliation. A randomized complete block design at the Swift Current Research and Development Centre (SCRDC) of Agriculture and Agri-Food Canada (AAFC) examined the effects of water stress and clipping on the plant biomass, plant morphological traits, and relative leaf chlorophyll content (SPAD value) of four native grasses (caespitose grass: Hesperostipa comata and H. curtiseta; rhizomatous grass: Pascopyrum smithii and Elymus lanceolatus). Drought drastically decreased the shoot and root biomass, plant height, number of tillers and leaf growth of P. smithii and E. lanceolatus, as well as the rhizome biomass and R/S ratio of P. smithii. Defoliation had a positive effect on the shoot biomass of P. smithii and E. lanceolatus under well water treatments (100% and 85% of field capacity). However, the compensatory growth of P. smithii and E. lanceolatus significantly declined with increased water stress. In addition, there are no significant changes in plant biomass, plant height, number of tillers and leaves, and SPAD value of H. comata and H. curtiseta under relative dry condition (70% of field capacity). Consequently, these results demonstrated that the rhizomatous grasses possessed a stronger compensation in response to defoliation under wet conditions, but the positive effects of defoliation can be weakened by drought. The caespitose grasses (Hesperostipa species) exhibited a greater drought tolerance than rhizomatous grasses due to the relatively stable plant traits in response to water stress.}, } @article {pmid30598804, year = {2018}, author = {Ellis, TD and Cushman, JH}, title = {Indirect effects of a large mammalian herbivore on small mammal populations: Context-dependent variation across habitat types, mammal species, and seasons.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12115-12125}, doi = {10.1002/ece3.4670}, pmid = {30598804}, issn = {2045-7758}, abstract = {Multiple consumer species frequently co-occur in the same landscape and, through effects on surrounding environments, can interact in direct and indirect ways. These interactions can vary in occurrence and importance, and focusing on this variation is critical for understanding the dynamics of interactions among consumers. Large mammalian herbivores are important engineers of ecosystems worldwide, have substantial impacts on vegetation, and can indirectly affect small-mammal populations. However, the degree to which such indirect effects vary within the same system has received minimal attention. We used a 16-year-old exclosure experiment, stratified across a heterogeneous landscape, to evaluate the importance of context-dependent interactions between tule elk (Cervus canadensis nannodes) and small mammals (deer mice [Peromyscus maniculatus], meadow voles [Microtus californicus], and harvest mice [Reithrodontymys megalotis]) in a coastal grassland in California. Effects of elk on voles varied among habitats and seasons: In open grasslands, elk reduced vole numbers during fall 2013 but not summer 2014; in Lupinus-dominated grasslands, elk reduced vole numbers during summer 2014 but not fall 2013; and in Baccharis-dominated grasslands, elk had no effect on vole numbers in either season. Effects of elk on the two mice species also varied among habitats and seasons, but often in different ways from voles and each other. In fall 2013, elk decreased mice abundances in Lupinus-dominated grasslands, but not in Baccharis-dominated or open grasslands. In summer 2014, elk decreased the abundance of harvest mice consistently across habitat types. In contrast, elk increased deer-mice numbers in open grasslands but not other habitats. Within the same heterogenous study system, the influence of elk on small mammals was strongly context-dependent, varying among habitats, mammal species, and seasons. We hypothesize that such variability is common in nature and that failure to consider it may yield inaccurate findings and limit our understanding of interactions among co-occurring consumers.}, } @article {pmid30598803, year = {2018}, author = {Barnard, AA and Masly, JP}, title = {Divergence in female damselfly sensory structures is consistent with a species recognition function but shows no evidence of reproductive character displacement.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12101-12114}, doi = {10.1002/ece3.4669}, pmid = {30598803}, issn = {2045-7758}, abstract = {Males and females transmit and receive signals prior to mating that convey information such as sex, species identity, or individual condition. In some animals, tactile signals relayed during physical contact between males and females before and during mating appear to be important for mate choice or reproductive isolation. This is common among odonates, when a male grasps a female's thorax with his terminal appendages prior to copulation, and the female subsequently controls whether copulation occurs by bending her abdomen to complete intromission. It has been hypothesized that mechanosensory sensilla on the female thoracic plates mediate mating decisions, but is has been difficult to test this idea. Here, we use North American damselflies in the genus Enallagma (Odonata: Coenagrionidae) to test the hypothesis that variation in female sensilla traits is important for species recognition. Enallagma anna and E. carunculatum hybridize in nature, but experience strong reproductive isolation as a consequence of divergence in male terminal appendage morphology. We quantified several mechanosensory sensilla phenotypes on the female thorax among multiple populations of both species and compared divergence in these traits in sympatry versus allopatry. Although these species differed in features of sensilla distribution within the thoracic plates, we found no strong evidence of reproductive character displacement among the sensilla traits we measured in regions of sympatry. Our results suggest that species-specific placement of female mechanoreceptors may be sufficient for species recognition, although other female sensory phenotypes might have diverged in sympatry to reduce interspecific hybridization.}, } @article {pmid30598802, year = {2018}, author = {Russell, K and Van Sanford, D}, title = {Breeding for resilience to increasing temperatures: A field trial assessing genetic variation in soft red winter wheat.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12090-12100}, doi = {10.1002/ece3.4668}, pmid = {30598802}, issn = {2045-7758}, abstract = {Breeding for resilience to climate change is a daunting prospect. Crop and climate models tell us that global wheat yields are likely to decline as the climate warms, causing a significant risk to global food security. High temperatures are known to affect crop development yet breeding for tolerance to heat stress is difficult to achieve in field environments. We conducted an active warming study over two years to quantify the effects of heat stress on genetic variation of soft red winter (SRW) wheat (Triticum aestivum L.). Forty SRW cultivars and breeding lines were chosen based on marker genotypes at photoperiod sensitivity and reduced height loci. These genotypes were planted in a randomized complete block design replicated twice across two environments, ambient and artificially warmed. Average heading date occurred 5 days earlier in the warmed environment than in the ambient environment over both years (p ≤ 0.05). On average, grain yield was significantly reduced in the warmed environment by 211.41 kg/ha (p ≤ 0.05) or 4.84%, though we identified 13 genotypes with increased yield in response to warming in both years. Of these genotypes, eight had significantly increased N uptake while six showed significantly increased N utilization efficiency under warming. Under warming, genotypes with wild-type alleles at the Rht-D1 locus display significantly greater yields (p ≤ 0.01) and biomass (p ≤ 0.001) than genotypes with reduced height alleles. Of the 13 genotypes with higher (p ≤ 0.01) yields under warming, nine have the wild-type allele at the Rht-D1 locus in addition to being photoperiod insensitive. The next steps will be to validate these findings in other populations and to develop an efficient breeding/phenotyping scheme that will lead to more resilient cultivars.}, } @article {pmid30598801, year = {2018}, author = {Yıldırım, Y and Tinnert, J and Forsman, A}, title = {Contrasting patterns of neutral and functional genetic diversity in stable and disturbed environments.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12073-12089}, doi = {10.1002/ece3.4667}, pmid = {30598801}, issn = {2045-7758}, abstract = {Genetic structure among and diversity within natural populations is influenced by a combination of ecological and evolutionary processes. These processes can differently influence neutral and functional genetic diversity and also vary according to environmental settings. To investigate the roles of interacting processes as drivers of population-level genetic diversity in the wild, we compared neutral and functional structure and diversity between 20 Tetrix undulata pygmy grasshopper populations in disturbed and stable habitats. Genetic differentiation was evident among the different populations, but there was no genetic separation between stable and disturbed environments. The incidence of long-winged phenotypes was higher in disturbed habitats, indicating that these populations were recently established by flight-capable colonizers. Color morph diversity and dispersion of outlier genetic diversity, estimated using AFLP markers, were higher in disturbed than in stable environments, likely reflecting that color polymorphism and variation in other functionally important traits increase establishment success. Neutral genetic diversity estimated using AFLP markers was lower in disturbed habitats, indicating stronger eroding effects on neutral diversity of genetic drift associated with founding events in disturbed compared to stable habitats. Functional diversity and neutral diversity were negatively correlated across populations, highlighting the utility of outlier loci in genetics studies and reinforcing that estimates of genetic diversity based on neutral markers do not infer evolutionary potential and the ability of populations and species to cope with environmental change.}, } @article {pmid30598800, year = {2018}, author = {Heinze, J and Hanoeffner, M and Delabie, JHC and Schrempf, A}, title = {Methuselah's daughters: Paternal age has little effect on offspring number and quality in Cardiocondyla ants.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12066-12072}, doi = {10.1002/ece3.4666}, pmid = {30598800}, issn = {2045-7758}, abstract = {Male age may directly or indirectly affect the fitness of their female mating partners and their joint progeny. While in some taxa of insects, old males make better mates and fathers, young males excel in others. Males of most social Hymenoptera are relatively short lived and because of testis degeneration have only a limited sperm supply. In contrast, the wingless fighter males of the ant Cardiocondyla obscurior live for several weeks and produce sperm throughout their lives. Wingless males engage in lethal combat with rival males and the winner of such fights can monopolize mating with all female sexuals that emerge in their nests over a prolonged timespan. Here, we investigate if male age has an influence on sperm quality, the queen's lifespan and productivity, and the size and weight of their offspring. Queens mated to one-week or six-week-old males did not differ in life expectancy and offspring production, but the daughters of young males were slightly heavier than those of old males. Our data suggest negligible reproductive senescence of C. obscurior males even at an age, which only few of them reach. This matches the reproductive strategy of Cardiocondyla ants, in which freshly emerging female sexuals rarely have the option to mate with males other than the one present in their natal nest.}, } @article {pmid30598799, year = {2018}, author = {Sandamal, S and Tennakoon, A and Meng, QL and Marambe, B and Ratnasekera, D and Melo, A and Ge, S}, title = {Population genetics and evolutionary history of the wild rice species Oryza rufipogon and O. nivara in Sri Lanka.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12056-12065}, doi = {10.1002/ece3.4665}, pmid = {30598799}, issn = {2045-7758}, abstract = {Genetic diversity and population genetic structure of the wild rice species Oryza rufipogon and O. nivara in Sri Lanka were studied using 33 microsatellite markers. A total of 315 individuals of 11 natural populations collected from the wet, intermediate, and dry zones of the country were used in the study. We found a moderate to high level of genetic diversity at the population level, with the polymorphic loci (P) ranging from 60.6% to 100% (average 81.8%) and the expected heterozygosity (HE) varying from 0.294 to 0.481 (average 0.369). A significant genetic differentiation between species and strong genetic structure within species were also observed. Based on species distribution modeling, we detected the dynamics of the preferred habitats for the two species in Sri Lanka and demonstrated that both O. rufipogon and O. nivara populations have expanded substantially since the last internal glacial. In addition, we showed that the geographical distribution of the two species corresponded to the climate zones and identified a few of key environmental variables that contribute to the distribution of the two species, implying the potential mechanism for ecological adaptation of these two species in Sri Lanka. These studies provided important insights into the population genetics and evolution of these wild species in Sri Lanka and are of great significance to the in situ conservation and utilization of these wild resources in genetic improvement of rice.}, } @article {pmid30598798, year = {2018}, author = {Rozins, C and Silk, MJ and Croft, DP and Delahay, RJ and Hodgson, DJ and McDonald, RA and Weber, N and Boots, M}, title = {Social structure contains epidemics and regulates individual roles in disease transmission in a group-living mammal.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12044-12055}, doi = {10.1002/ece3.4664}, pmid = {30598798}, issn = {2045-7758}, abstract = {Population structure is critical to infectious disease transmission. As a result, theoretical and empirical contact network models of infectious disease spread are increasingly providing valuable insights into wildlife epidemiology. Analyzing an exceptionally detailed dataset on contact structure within a high-density population of European badgers Meles meles, we show that a modular contact network produced by spatially structured stable social groups, lead to smaller epidemics, particularly for infections with intermediate transmissibility. The key advance is that we identify considerable variation among individuals in their role in disease spread, with these new insights made possible by the detail in the badger dataset. Furthermore, the important impacts on epidemiology are found even though the modularity of the Badger network is much lower than the threshold that previous work suggested was necessary. These findings reveal the importance of stable social group structure for disease dynamics with important management implications for socially structured populations.}, } @article {pmid30598797, year = {2018}, author = {Savva, I and Bennett, S and Roca, G and Jordà, G and Marbà, N}, title = {Thermal tolerance of Mediterranean marine macrophytes: Vulnerability to global warming.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12032-12043}, doi = {10.1002/ece3.4663}, pmid = {30598797}, issn = {2045-7758}, abstract = {The Mediterranean Sea is warming at three times the rate of the global ocean raising concerns about the vulnerability of marine organisms to climate change. Macrophytes play a key role in coastal ecosystems, therefore predicting how warming will affect these key species is critical to understand the effects of climate change on Mediterranean coastal ecosystems. We measured the physiological performance of six dominant native Mediterranean macrophytes under ten temperature treatments ranging from 12 to 34°C to examine their thermal niche, and vulnerability to projected warming in the western Mediterranean up until 2100. Among the macrophytes tested, Cymodocea nodosa was the species with the highest thermal optima and it was beyond current summer temperature. Therefore, C. nodosa may benefit from projected warming over the coming century. The optimal temperature for growth of the other species (Posidonia oceanica, Cystoseira compressa, Padina pavonica, Caulerpa prolifera, and Halimeda tuna) was lower. Similarly, the species presented different upper lethal limits, spanning at least across 5.1°C between 28.9°C (P. oceanica) and >34°C (C. nodosa). Our results demonstrate the variable physiological responses of species within the same local community to temperature changes and highlight important potential differences in climate change vulnerability, among species within coastal marine ecosystems.}, } @article {pmid30598796, year = {2018}, author = {Martinez, AS and Willoughby, JR and Christie, MR}, title = {Genetic diversity in fishes is influenced by habitat type and life-history variation.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12022-12031}, doi = {10.1002/ece3.4661}, pmid = {30598796}, issn = {2045-7758}, abstract = {Populations of fishes are increasingly threatened by over-exploitation, pollution, habitat destruction, and climate change. In order to better understand the factors that can explain the amount of genetic diversity in wild populations of fishes, we collected estimates of genetic diversity (mean heterozygosity and mean rarefied number of alleles per locus) along with habitat associations, conservation status, and life-history information for 463 fish species. We ran a series of phylogenetic generalized least squares models to determine which factors influence genetic diversity in fishes after accounting for shared evolutionary history among related taxa. We found that marine fishes had significantly higher genetic diversity than freshwater fishes with marine fishes averaging 11.3 more alleles per locus than their freshwater counterparts. However, contrary to our expectations, genetic diversity was not found to be lower in threatened versus not-threatened fishes. Finally, we found that both age at maturity and fecundity were negatively related to genetic variation in both marine and freshwater fishes. Our results demonstrate that both life-history characteristics and habitat play a role in shaping patterns of genetic diversity in fishes and should be considered when prioritizing species for conservation.}, } @article {pmid30598795, year = {2018}, author = {Lonsinger, RC and Adams, JR and Waits, LP}, title = {Evaluating effective population size and genetic diversity of a declining kit fox population using contemporary and historical specimens.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {12011-12021}, doi = {10.1002/ece3.4660}, pmid = {30598795}, issn = {2045-7758}, abstract = {Loss of genetic diversity has serious conservation consequences (e.g., loss of adaptive potential, reduced population viability), but is difficult to evaluate without developing long-term, multigenerational datasets. Alternatively, historical samples can provide insights into changes in genetic diversity and effective population size (Ne). Kit foxes (Vulpes macrotis) are a species of conservation concern across much of their range. In western Utah, kit fox abundance has declined precipitously from historical levels, causing concern about population persistence. We analyzed genetic samples from museum specimens and contemporary scats to evaluate temporal changes in (a) genetic diversity and (b) Ne for kit foxes in western Utah, and (c) discuss our findings with respect to population risk and conservation. The Ne of kit foxes in western Utah has decreased substantially. When compared to established conservation thresholds for Ne (e.g., the 50/500 rule), observed levels suggest the population may be at risk of inbreeding depression and local extinction. In contrast, we found no significant decrease in genetic diversity associated with declining Ne. We detected evidence of low levels of immigration into the population and suspect genetic diversity may have been maintained by this previously undescribed gene flow from adjacent populations. Low or intermittent immigration may serve to temper the potential short-term negative consequences of low Ne. We recommend that kit fox conservation efforts focus on evaluating and maintaining landscape connectivity. We demonstrate how historical specimens can provide a baseline of comparison for contemporary populations, highlighting the importance of natural history collections to conservation during a period of declining funding and support.}, } @article {pmid30598794, year = {2018}, author = {Alhassan, AM and Ma, W and Li, G and Jiang, Z and Wu, J and Chen, G}, title = {Response of soil organic carbon to vegetation degradation along a moisture gradient in a wet meadow on the Qinghai-Tibet Plateau.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11999-12010}, doi = {10.1002/ece3.4656}, pmid = {30598794}, issn = {2045-7758}, abstract = {The study was conducted during the growing seasons of 2013, 2014, and 2015 in the wet meadows on the eastern Qinghai-Tibet plateau (QTP) in the Gansu Gahai Wetland Nature Reserve to determine the dynamics of soil organic carbon (SOC) as affected by vegetation degradation along a moisture gradient and to assess its relationship with other soil properties and biomass yield. Hence, we measured SOC at depths of 0-10, 10-20, and 20-40 cm under the influence of four categories of vegetation degradation (healthy vegetation [HV], slightly degraded [SD], moderately degraded [MD], and heavily degraded [HD]). Our results showed that SOC decreased with increased degree of vegetation degradation. Average SOC content ranged between 36.18 ± 4.06 g/kg in HD and 69.86 ± 21.78 g/kg in HV. Compared with HV, SOC content reduced by 30.49%, 42.22%, and 48.22% in SD, MD, and HD, respectively. SOC significantly correlated positively with soil water content, aboveground biomass, and belowground biomass, but significantly correlated negatively with soil temperature and bulk density (p < 0.05). Highly Significant positive correlations were also found between SOC and total nitrogen (p = 0.0036), total phosphorus (p = 0.0006) and total potassium (p < 0.0001). Our study suggests that severe vegetation and moisture loss led to approximately 50% loss in SOC content in the wet meadows, implying that under climate warming, vegetation and soil moisture loss will dramatically destabilize carbon sink capacities of wetlands. We therefore suggest wetland hydrological management, restoration of vegetation, plant species protection, regulation of grazing activities, and other anthropogenic activities to stabilize carbon sink capacities of wetlands.}, } @article {pmid30598793, year = {2018}, author = {Feng, G and Li, JQ and Zang, RG and Ding, Y and Ai, XR and Yao, L}, title = {Variation in three community features across habitat types and scales within a 15-ha subtropical evergreen-deciduous broadleaved mixed forest dynamics plot in China.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11987-11998}, doi = {10.1002/ece3.4655}, pmid = {30598793}, issn = {2045-7758}, abstract = {The evergreen and deciduous broadleaved mixed forests (EDBMFs) belong to one of the ecosystems most sensitive to environmental change, however, little is known about the environmental determinants for their plant diversity and forest structure at different habitat types and spatial scales. Here, we used data from a 15-ha (300 × 500 m) forest dynamic plot (FDP) of an old-growth EDBMF to examine the patterns and determinants of the three community features (stem abundance, rarefied species richness and basal area [BA]) in three habitat types (ridge, hillside and foothill) and at three spatial scales (20 × 20 m, 50 × 50 m, and 100 × 100 m). We found that the three community features significantly changed with habitat type, but only one of them (rarefied richness) changed with scale. Among spatial scales, the principle environmental factors that widely affected community features were pH, soil organic matter, and total phosphorus, while these effects only taken place at certain habitat. Variations in the three community features explained by soil conditions were generally greater than those explained by topographical conditions. With changes in habitat type, the proportion of variations explained by environmental conditions was 31%-53%, 8%-25%, and 18%-26% for abundance, rarefied richness, and BA, respectively. With increasing spatial scale, the variations explained by environmental conditions were 44%-75% for abundance, 28%-95% for rarefied richness, and 18%-86% for BA. Our study demonstrated that environmental factors had great impacts on the plant diversity and forest structure in the EDBMFs, especially the soil factors such as pH. In addition, the importance of the environmental determinants on these community features was highly related to the spatial scale.}, } @article {pmid30598792, year = {2018}, author = {Alexander, HM and Collins, CD and Reed, AW and Kettle, WD and Collis, DA and Christiana, LD and Salisbury, VB}, title = {Effects of removing woody cover on long-term population dynamics of a rare annual plant (Agalinis auriculata): A study comparing remnant prairie and oldfield habitats.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11975-11986}, doi = {10.1002/ece3.4654}, pmid = {30598792}, issn = {2045-7758}, abstract = {Worldwide, grasslands are becoming shrublands/forests. In North America, eastern red cedar (Juniperus virginiana) often colonizes prairies. Habitat management can focus on woody removal, but we often lack long-term data on whether removal leads to population recovery of herbaceous plants without seeding. We undertook a long-term study (17 years) of numbers of the rare annual plant Agalinis auriculata in a gridwork of 100 m2 plots in adjacent prairie and oldfield sites in Kansas, USA. We collected data before and after removal of Juniperus virginiana at the prairie. Plant population sizes were highly variable at both sites and over time. High numbers of plants in a plot 1 year were often followed by low numbers the following year, suggesting negative density-dependence. Plant numbers were lowest with extensive woody cover and with low precipitation. After woody plant removal, A. auriculata increased dramatically in abundance and occupancy in most years; increases were also seen at the oldfield, suggesting later survey years were overall more favorable. Synthesis and applications: Removal of woody plants led to increased numbers of a rare annual prairie plant, without seeding. Multiple years of data were essential for interpretation given extreme temporal variability in numbers. The largest prairie population was 7 years following tree removal, showing that positive effects of management can last this long. This species also fared well in oldfield habitat, suggesting restoration opportunities. Given that land managers are busy, time-efficient field methods and data analysis approaches such as ours offer advantages. In addition to general linear models, we suggest Rank Occupancy-Abundance Profiles (ROAPs), a simple-to-use data visualization and analysis method. Creation of ROAPs for sites before and after habitat management helps reveal the degree to which plant populations are responding to management with changes in local density, changes in occupancy, or both.}, } @article {pmid30598791, year = {2018}, author = {Maruyama, A and Sugatani, K and Watanabe, K and Yamanaka, H and Imamura, A}, title = {Environmental DNA analysis as a non-invasive quantitative tool for reproductive migration of a threatened endemic fish in rivers.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11964-11974}, doi = {10.1002/ece3.4653}, pmid = {30598791}, issn = {2045-7758}, abstract = {Quantitative information regarding reproduction is essential for conserving endangered animals; however, some conventional quantitative methods can be damaging to the target population and their habitats. In the present study, the reproductive migration of a threatened endemic fish, three-lips (Opsariichthys uncirostris uncirostris), was non-invasively monitored by quantitative PCR of species-specific environmental DNA (eDNA), the usefulness of which has been not sufficiently explored. Water sampling and from-shore visual inspection were performed weekly along a tributary of Lake Biwa (Japan), where adult fish seasonally migrate upstream to reproduce as well as at lake sites near the river mouth. Species-specific eDNA was collected at all locations at times when the fish were visually observed and at certain sites where the fish were not observed. Log-transformed individual counts from visual inspection were positively correlated with log-transformed eDNA concentration in the river sites, indicating that eDNA analysis can be a reliable quantitative tool for fish abundance in rivers. Furthermore, distance from the lake did not influence eDNA concentration, suggesting that eDNA transport by river flow had a negligible effect on eDNA quantification. Both eDNA concentration and individual counts gradually increased from May-July, and decreased in August. Importantly, eDNA analysis showed that the fish occupied more habitats in the peak reproductive season and stayed for longer time at any given site. An additional underwater survey confirmed unexpected eDNA detections as true positives. eDNA analysis has great potential to quantitatively monitor reproductive fish migrations under certain conditions.}, } @article {pmid30598790, year = {2018}, author = {Gao, S and Zheng, Z and Wang, Y and Liu, L and Zhao, N and Gao, Y}, title = {Drought and grazing drive the retrogressive succession by changing the plant-plant interaction of the main species in Inner Mongolia Steppe.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11954-11963}, doi = {10.1002/ece3.4652}, pmid = {30598790}, issn = {2045-7758}, abstract = {Plant-plant interactions play a key role in the function and structure of communities. The combined effect of drought stress and grazing disturbance on shaping plant-plant interactions is still poorly understood, while this combination is common in semiarid ecosystems. Four species including Stipa grandis, which is dominant in the typical steppe, and Stipa krylovii, Artemisia frigida, and Cleistogenes squarrosa, which are dominant species in the S. grandis degraded communities, were selected as study targets. We conducted a competition experiment (uniformly dense monoculture or mixture, respectively) under controlled conditions, including both drought stress and mowing disturbance, and calculated the relative interaction index (RII) of tiller number and RII of biomass for each species under each condition. (a) Under the same condition, the RII of tiller number and that of biomass for the same species usually showed reverse trends. (b) Mowing disturbance rather than drought stress played a negative role in influencing S. grandis' or S. krylovii's RII of tiller number and played a positive role in influencing A. frigida's RII of biomass. (c) Drought stress rather than mowing disturbance played a positive role in influencing C. squarrosa's RII of tiller number. (d) Neighbor species significantly influenced S. grandis' RII of tiller number, S. krylovii's RII of tiller number, A. frigida's RII of tiller number and biomass, and C. squarrosa's RII of biomass. These results could provide an explanation for why S. krylovii, A. frigida, and C. squarrosa can replace S. grandis and become the dominant species when S. grandis communities undergo a process of degradation due to overgrazing or climatic drought in natural communities. The present study provided powerful evidences for species replacement in the typical steppe of Inner Mongolia and elucidated the driving mechanisms of S. grandis communities' retrogressive succession.}, } @article {pmid30598789, year = {2018}, author = {Hulsey, CD and Holzman, R and Meyer, A}, title = {Dissecting a potential spandrel of adaptive radiation: Body depth and pectoral fin ecomorphology coevolve in Lake Malawi cichlid fishes.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11945-11953}, doi = {10.1002/ece3.4651}, pmid = {30598789}, issn = {2045-7758}, abstract = {The evolution of body shape reflects both the ecological factors structuring organismal diversity as well as an organism's underlying anatomy. For instance, body depth in fishes is thought to determine their susceptibility to predators, attractiveness to mates, as well as swimming performance. However, the internal anatomy influencing diversification of body depth has not been extensively examined, and changes in body depth could arise as a by-product of functional changes in other anatomical structures. Using an improved phylogenetic hypothesis for a diverse set of Lake Malawi cichlid fishes, we tested the evolutionary association between body depth and the height of the pectoral girdle. To refine the functional importance of the observed substantial correlation, we also tested the coevolution of pectoral girdle height and pectoral fin area. The extensive coevolution of these traits suggests body depth in fishes like the Lake Malawi cichlids could diverge simply as a by-product of being tightly linked to ecomorphological divergence in other functional morphological structures like the pectoral fins.}, } @article {pmid30598788, year = {2018}, author = {Prates, I and Penna, A and Rodrigues, MT and Carnaval, AC}, title = {Local adaptation in mainland anole lizards: Integrating population history and genome-environment associations.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11932-11944}, doi = {10.1002/ece3.4650}, pmid = {30598788}, issn = {2045-7758}, abstract = {Environmental gradients constrain physiological performance and thus species' ranges, suggesting that species occurrence in diverse environments may be associated with local adaptation. Genome-environment association analyses (GEAA) have become central for studies of local adaptation, yet they are sensitive to the spatial orientation of historical range expansions relative to landscape gradients. To test whether potentially adaptive genotypes occur in varied climates in wide-ranged species, we implemented GEAA on the basis of genomewide data from the anole lizards Anolis ortonii and Anolis punctatus, which expanded from Amazonia, presently dominated by warm and wet settings, into the cooler and less rainy Atlantic Forest. To examine whether local adaptation has been constrained by population structure and history, we estimated effective population sizes, divergence times, and gene flow under a coalescent framework. In both species, divergence between Amazonian and Atlantic Forest populations dates back to the mid-Pleistocene, with subsequent gene flow. We recovered eleven candidate genes involved with metabolism, immunity, development, and cell signaling in A. punctatus and found no loci whose frequency is associated with environmental gradients in A. ortonii. Distinct signatures of adaptation between these species are not associated with historical constraints or distinct climatic space occupancies. Similar patterns of spatial structure between selected and neutral SNPs along the climatic gradient, as supported by patterns of genetic clustering in A. punctatus, may have led to conservative GEAA performance. This study illustrates how tests of local adaptation can benefit from knowledge about species histories to support hypothesis formulation, sampling design, and landscape gradient characterization.}, } @article {pmid30598787, year = {2018}, author = {Ng, WT and Cândido de Oliveira Silva, A and Rima, P and Atzberger, C and Immitzer, M}, title = {Ensemble approach for potential habitat mapping of invasive Prosopis spp. in Turkana, Kenya.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11921-11931}, doi = {10.1002/ece3.4649}, pmid = {30598787}, issn = {2045-7758}, abstract = {Aim: Prosopis spp. are an invasive alien plant species native to the Americas and well adapted to thrive in arid environments. In Kenya, several remote-sensing studies conclude that the genus is well established throughout the country and is rapidly invading new areas. This research aims to model the potential habitat of Prosopis spp. by using an ensemble model consisting of four species distribution models. Furthermore, environmental and expert knowledge-based variables are assessed.

Location: Turkana County, Kenya.

Methods: We collected and assessed a large number of environmental and expert knowledge-based variables through variable correlation, collinearity, and bias tests. The variables were used for an ensemble model consisting of four species distribution models: (a) logistic regression, (b) maximum entropy, (c) random forest, and (d) Bayesian networks. The models were evaluated through a block cross-validation providing statistical measures.

Results: The best predictors for Prosopis spp. habitat are distance from water and built-up areas, soil type, elevation, lithology, and temperature seasonality. All species distribution models achieved high accuracies while the ensemble model achieved the highest scores. Highly and moderately suitable Prosopis spp. habitat covers 6% and 9% of the study area, respectively.

Main conclusions: Both ensemble and individual models predict a high risk of continued invasion, confirming local observations and conceptions. Findings are valuable to stakeholders for managing invaded area, protecting areas at risk, and to raise awareness.}, } @article {pmid30598786, year = {2018}, author = {Kuszewska, K and Miler, K and Rojek, W and Ostap-Chęć, M and Woyciechowski, M}, title = {Rebel honeybee workers have a tendency to become intraspecific reproductive parasites.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11914-11920}, doi = {10.1002/ece3.4647}, pmid = {30598786}, issn = {2045-7758}, abstract = {Worker honeybees may reproduce in either their own or foreign colonies; the latter situation is termed intraspecific reproductive parasitism (IRP). In this study, we compared the tendency for IRP between normal honeybee workers, which are characterized by a relatively low reproductive potential, and "rebel workers", a recently discovered subcaste of honeybee workers characterized by a high reproductive potential that develops when the colony is without a queen. We expected that the high reproductive potential of the rebel workers would influence their reproductive strategy and that these individuals would drift to other colonies to lay eggs more often than normal workers. The results confirm our expectations and show that rebel workers are more likely than normal workers to drift to foreign colonies. The rebel workers also preferred to drift to queenless colonies than to queenright colonies, while the normal workers did not show this preference. This study indicates that rebel workers have a tendency for IRP, which may be responsible for the maintenance of the rebel worker strategy in bee populations.}, } @article {pmid30598785, year = {2018}, author = {Tavares, SB and Samarra, FIP and Pascoal, S and Graves, JA and Miller, PJO}, title = {Killer whales (Orcinus orca) in Iceland show weak genetic structure among diverse isotopic signatures and observed movement patterns.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11900-11913}, doi = {10.1002/ece3.4646}, pmid = {30598785}, issn = {2045-7758}, abstract = {Local adaption through ecological niche specialization can lead to genetic structure between and within populations. In the Northeast Pacific, killer whales (Orcinus orca) of the same population have uniform specialized diets that are non-overlapping with other sympatric, genetically divergent, and socially isolated killer whale ecotypes. However, killer whales in Iceland show intrapopulation variation of isotopic niches and observed movement patterns: some individuals appear to specialize on herring and follow it year-round while others feed upon herring only seasonally or opportunistically. We investigated genetic differentiation among Icelandic killer whales with different isotopic signatures and observed movement patterns. This information is key for management and conservation purposes but also for better understanding how niche specialization drives genetic differentiation. Photo-identified individuals (N = 61) were genotyped for 22 microsatellites and a 611 bp portion of the mitochondrial DNA (mtDNA) control region. Photo-identification of individuals allowed linkage of genetic data to existing data on individual isotopic niche, observed movement patterns, and social associations. Population subdivision into three genetic units was supported by a discriminant analysis of principal components (DAPC). Genetic clustering corresponded to the distribution of isotopic signatures, mtDNA haplotypes, and observed movement patterns, but genetic units were not socially segregated. Genetic differentiation was weak (FST < 0.1), suggesting ongoing gene flow or recent separation of the genetic units. Our results show that killer whales in Iceland are not as genetically differentiated, ecologically discrete, or socially isolated as the Northeast Pacific prey-specialized killer whales. If any process of ecological divergence and niche specialization is taking place among killer whales in Iceland, it is likely at a very early stage and has not led to the patterns observed in the Northeast Pacific.}, } @article {pmid30598784, year = {2018}, author = {Su, J and Aryal, A and Hegab, IM and Shrestha, UB and Coogan, SCP and Sathyakumar, S and Dalannast, M and Dou, Z and Suo, Y and Dabu, X and Fu, H and Wu, L and Ji, W}, title = {Decreasing brown bear (Ursus arctos) habitat due to climate change in Central Asia and the Asian Highlands.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11887-11899}, doi = {10.1002/ece3.4645}, pmid = {30598784}, issn = {2045-7758}, abstract = {Around the world, climate change has impacted many species. In this study, we used bioclimatic variables and biophysical layers of Central Asia and the Asian Highlands combined with presence data of brown bear (Ursus arctos) to understand their current distribution and predict their future distribution under the current rate of climate change. Our bioclimatic model showed that the current suitable habitat of brown bear encompasses 3,430,493 km2 in the study area, the majority of which (>65%) located in China. Our analyses demonstrated that suitable habitat will be reduced by 11% (378,861.30 km2) across Central Asia and the Asian Highlands by 2,050 due to climate change, predominantly (>90%) due to the changes in temperature and precipitation. The spatially averaged mean annual temperature of brown bear habitat is currently -1.2°C and predicted to increase to 1.6°C by 2,050. Mean annual precipitation in brown bear habitats is predicted to increase by 13% (from 406 to 459 mm) by 2,050. Such changes in two critical climatic variables may significantly affect the brown bear distribution, ethological repertoires, and physiological processes, which may increase their risk of extirpation in some areas. Approximately 32% (1,124,330 km2) of the total suitable habitat falls within protected areas, which was predicted to reduce to 1,103,912 km2 (1.8% loss) by 2,050. Future loss of suitable habitats inside the protected areas may force brown bears to move outside the protected areas thereby increasing their risk of mortality. Therefore, more protected areas should be established in the suitable brown bear habitats in future to sustain populations in this region. Furthermore, development of corridors is needed to connect habitats between protected areas of different countries in Central Asia. Such practices will facilitate climate migration and connectivity among populations and movement between and within countries.}, } @article {pmid30598783, year = {2018}, author = {Ackiss, AS and Bird, CE and Akita, Y and Santos, MD and Tachihara, K and Carpenter, KE}, title = {Genetic patterns in peripheral marine populations of the fusilier fish Caesio cuning within the Kuroshio Current.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11875-11886}, doi = {10.1002/ece3.4644}, pmid = {30598783}, issn = {2045-7758}, abstract = {Aim: Mayr's central-peripheral population model (CCPM) describes the marked differences between central and peripheral populations in genetic diversity, gene flow, and census size. When isolation leads to genetic divergence, these peripheral populations have high evolutionary value and can influence biogeographic patterns. In tropical marine species with pelagic larvae, powerful western-boundary currents have great potential to shape the genetic characteristics of peripheral populations at latitudinal extremes. We tested for the genetic patterns expected by the CCPM in peripheral populations that are located within the Kuroshio Current for the Indo-Pacific reef fish, Caesio cuning.

Methods: We used a panel of 2,677 SNPs generated from restriction site-associated DNA (RAD) sequencing to investigate genetic diversity, relatedness, effective population size, and spatial patterns of population connectivity from central to peripheral populations of C. cuning along the Kuroshio Current.

Results: Principal component and cluster analyses indicated a genetically distinct lineage at the periphery of the C. cuning species range and examination of SNPs putatively under divergent selection suggested potential for local adaptation in this region. We found signatures of isolation-by-distance and significant genetic differences between nearly all sites. Sites closest to the periphery exhibited increased within-population relatedness and decreased effective population size.

Main Conclusions: Despite the potential for homogenizing gene flow along the Kuroshio Current, peripheral populations in C. cuning conform to the predictions of the CCPM. While oceanography, habitat availability, and dispersal ability are all likely to shape the patterns found in C. cuning across this central-peripheral junction, the impacts of genetic drift and natural selection in increasing smaller peripheral populations appear to be probable influences on the lineage divergence found in the Ryukyu Islands.}, } @article {pmid30598782, year = {2018}, author = {Shero, MR and Goetz, KT and Costa, DP and Burns, JM}, title = {Temporal changes in Weddell seal dive behavior over winter: Are females increasing foraging effort to support gestation?.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11857-11874}, doi = {10.1002/ece3.4643}, pmid = {30598782}, issn = {2045-7758}, abstract = {In capital-breeding marine mammals, prey acquisition during the foraging trip coinciding with gestation must provide energy to meet the immediate needs of the growing fetus and also a store to meet the subsequent demands of lactation. Weddell seals (Leptonychotes weddellii) that give birth following the gestational (winter) foraging period gain similar proportions of mass and lipid as compared to females that fail to give birth. Therefore, any changes in foraging behavior can be attributed to gestational costs. To investigate differences in foraging effort associated with successful reproduction, twenty-three satellite tags were deployed on post-molt female Weddell seals in the Ross Sea. Of the 20 females that returned to the area the following year, 12 females gave birth and eight did not. Females that gave birth the following year began the winter foraging period with significantly longer and deeper dives, as compared to non-reproductive seals. Mid- to late winter, reproductive females spent a significantly greater proportion of the day diving, and either depressed their diving metabolic rates (DMR), or exceeded their calculated aerobic dive limit (cADL) more frequently than females that returned without a pup. Moreover, non-reproductive females organized their dives into 2-3 short bouts per day on average (BOUTshort; 7.06 ± 1.29 hr; mean ± 95% CI), whereas reproductive females made 1-2 BOUTshort per day (10.9 ± 2.84 hr), comprising one long daily foraging bout without rest. The magnitude of the increase in dive activity budgets and depression in calculated DMR closely matched the estimated energetic requirements of supporting a fetus. This study is one of the first to identify increases in foraging effort that are associated with successful reproduction in a top predator and indicates that reproductive females must operate closer to their physiological limits to support gestational costs.}, } @article {pmid30598781, year = {2018}, author = {Lal, R and Kininmonth, S and N'Yeurt, ADR and Riley, RH and Rico, C}, title = {The effects of a stressed inshore urban reef on coral recruitment in Suva Harbour, Fiji.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11842-11856}, doi = {10.1002/ece3.4641}, pmid = {30598781}, issn = {2045-7758}, abstract = {A relic inshore reef ecosystem adjacent to the Fijian capital of Suva and another remote inshore reef were monitored monthly from July 2014 to July 2015 for coral recruitment, sedimentation rates, coral cover, temperature, and light intensity. Despite a major sewage spill in Suva Harbour in December 2014, the municipal inshore site exposed to constant anthropogenic activity, recorded no significant differences in coral spat abundance (except for the family Poritidae) on artificial substrata compared to the remote inshore site. Total yearly spat abundance was 106 on municipal reef and 132 on remote reef, while average daily sediment trap collection rates (g cm2/day) were significantly higher in the municipal site for the entire duration of monitoring. Total annual particulate organic matter content in sediment was also significantly higher in the municipal site (107.51 g cm2), compared to the remote site (43.37 g cm2). Mean light intensity was significantly lower for the municipal site (69.81 lum/ft2) compared to the remote site (239.26 lum/ft2), with Photosynthetically Active Radiation also lower for the former (800-1,066.66 µmol m-2 s-1) compared to the latter (3,266.66-3,600 µmol m-2 s-1). The lack of significant differences in coral spat recruitment rates suggests that settling larvae may be unable to distinguish between sub-optimal and optimal sites probably as a consequence of interference with coral settlement cues arising from anthropogenic development.}, } @article {pmid30598780, year = {2018}, author = {Kimmitt, AA and Dietz, SL and Reichard, DG and Ketterson, ED}, title = {Male courtship preference during seasonal sympatry may maintain population divergence.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11833-11841}, doi = {10.1002/ece3.4640}, pmid = {30598780}, issn = {2045-7758}, abstract = {Animal migration can lead to a population distribution known as seasonal sympatry, in which closely-related migrant and resident populations of the same species co-occur in sympatry during part of the year, but are otherwise allopatric. During seasonal sympatry in early spring, residents may initiate reproduction before migrants depart, presenting an opportunity for gene flow. Differences in reproductive timing between migrant and resident populations may favor residents that exhibit preferences for potential mates of similar migratory behavior and reproductive timing, thus maintaining population divergence. We studied dark-eyed juncos (Junco hyemalis), a songbird that exhibits seasonal sympatry. We conducted simulated courtship interactions in which we presented free-living resident males with either a caged migrant or resident female and quantified courtship behavior prior to the departure of the migrants. We found that resident males preferred to court resident females: they sang more short-range songs and exhibited more visual displays associated with courtship when presented with resident females. We conclude that males distinguish between migrant and resident females during seasonal sympatry when the risk of interacting with non-reproductive, migrant females is high. Male mate choice in seasonal sympatry is likely adaptive for male reproductive success. As a secondary effect, male mating preference could act to maintain or promote divergence between populations that differ in migratory strategy.}, } @article {pmid30598779, year = {2018}, author = {Soh, BSB and Kekeunou, S and Nanga Nanga, S and Dongmo, M and Rachid, H}, title = {Effect of temperature on the biological parameters of the cabbage aphid Brevicoryne brassicae.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11819-11832}, doi = {10.1002/ece3.4639}, pmid = {30598779}, issn = {2045-7758}, abstract = {The cabbage aphid, Brevicoryne brassicae, is a pest of many plants of the Brassicaceae family including cabbage, Brassica oleracea Linnaeus, 1753. We investigated the effect of temperature on the biological parameters of B. brassicae using different temperature-based models incorporated in the Insect Life Cycle Modelling (ILCYM) software. Nymphs of first stage were individually placed in the incubators successively set at 10°C, 15°C, 20°C, 25°C, 30°C, and 35°C; 75 ± 5% RH; and L12: D12-hr photoperiods. We found that first nymph reached the adult stage after 18.45 ± 0.04 days (10°C), 10.37 ± 0.26 days (15°C), 6.42 ± 0.07 days (20°C), 5.076 ± 0.09 days (25°C), and 5.05 ± 0.10 days (30°C), and failed at 35°C. The lower lethal temperatures for B. brassicae were 1.64°C, 1.57°C, 1.56°C, and 1.62°C with a thermal constant for development of 0.88, 0.87, and 0.08, 0.79 degree/day for nymphs I, II, III, and IV, respectively. The temperatures 10, 30, and 35°C were more lethal than 15, 20, and 25°C. Longevity was highest at 10°C (35.07 ± 1.38 days). Fertility was nil at 30°C and highest at 20°C (46.36 ± 1.73 nymphs/female). The stochastic simulation of the models obtained from the precedent biological parameters revealed that the life table parameters of B. brassicae were affected by the temperature. The net reproduction rate was highest at 20°C and lowest at 30°C. The average generation time decreased from 36.85 ± 1.5 days (15°C) to 6.86 ± 0.1 days (30°C); the intrinsic rate of increase and the finite rate of increase were highest at 25°C. In general, the life cycle data and mathematical functions obtained in this study clearly illustrate the effect of temperature on the biology of B. brassicae. This knowledge will contribute to predicting the changes that may occur in a population of B. Brassiace in response to temperature variation.}, } @article {pmid30598778, year = {2018}, author = {Christie, KS and Hollmen, TE and Flint, P and Douglas, D}, title = {Non-linear effect of sea ice: Spectacled Eider survival declines at both extremes of the ice spectrum.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11808-11818}, doi = {10.1002/ece3.4637}, pmid = {30598778}, issn = {2045-7758}, abstract = {Understanding the relationship between environmental factors and vital rates is an important step in predicting a species' response to environmental change. Species associated with sea ice are of particular concern because sea ice is projected to decrease rapidly in polar environments with continued levels of greenhouse gas emissions. The relationship between sea ice and the vital rates of the Spectacled Eider, a threatened species that breeds in Alaska and Russia and winters in the Bering Sea, appears to be complex. While severe ice can impede foraging for benthic prey, ice also suppresses wave action and provides a platform on which eiders roost, thereby reducing thermoregulation costs. We analyzed a 23-year mark-recapture dataset for Spectacled Eiders nesting on Kigigak Island in western Alaska, and tested survival models containing different ice and weather-related covariates. We found that much of the variation in eider survival could be explained by the number of days per year with >95% sea ice concentration at the Bering Sea core wintering area. Furthermore, the data supported a quadratic relationship with sea ice rather than a linear one, indicating that intermediate sea ice concentrations were optimal for survival. We then used matrix population models to project population trajectories using General Circulation Model (GCM) outputs of daily sea ice cover. GCMs projected reduced sea ice at the wintering area by year 2100 under a moderated emissions scenario (RCP 4.5) and nearly ice-free conditions under an unabated emissions scenario (RCP 8.5). Under RCP 4.5, stochastic models projected an increase in population size until 2069 coincident with moderate ice conditions, followed by a decline in population size as ice conditions shifted from intermediate to mostly ice-free. Under RCP 8.5, eider abundance increased until 2040 and then decreased to near extirpation toward the end of the century as the Bering Sea became ice-free. Considerable uncertainty around parameter estimates for survival in years with minimal sea ice contributed to variation in stochastic projections of future population size, and this uncertainty could be reduced with additional survival data from low-ice winters.}, } @article {pmid30598777, year = {2018}, author = {Xia, Z and Johansson, ML and Gao, Y and Zhang, L and Haffner, GD and MacIsaac, HJ and Zhan, A}, title = {Conventional versus real-time quantitative PCR for rare species detection.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11799-11807}, doi = {10.1002/ece3.4636}, pmid = {30598777}, issn = {2045-7758}, abstract = {Detection of species in nature at very low abundance requires innovative methods. Conventional PCR (cPCR) and real-time quantitative PCR (qPCR) are two widely used approaches employed in environmental DNA (eDNA) detection, though lack of a comprehensive comparison of them impedes method selection. Here we test detection capacity and false negative rate of both approaches using samples with different expected complexities. We compared cPCR and qPCR to detect invasive, biofouling golden mussels (Limnoperna fortunei), in samples from laboratory aquaria and irrigation channels where this mussel was known to occur in central China. Where applicable, the limit of detection (LoD), limit of quantification (LoQ), detection rate, and false negative rate of each PCR method were tested. Quantitative PCR achieved a lower LoD than cPCR (1 × 10-7 vs. 10-6 ng/μl) and had a higher detection rate for both laboratory (100% vs. 87.9%) and field (68.6% vs. 47.1%) samples. Field water samples could only be quantified at a higher concentration than laboratory aquaria and total genomic DNA, indicating inhibition with environmental samples. The false negative rate was inversely related to the number of sample replicates. Target eDNA concentration was negatively related to distance from sampling sites to the water (and animal) source. Detection capacity difference between cPCR and qPCR for genomic DNA and laboratory aquaria can be translated to field water samples, and the latter should be prioritized in rare species detection. Field environmental samples may involve more complexities-such as inhibitors-than laboratory aquaria samples, requiring more target DNA. Extensive sampling is critical in field applications using either approach to reduce false negatives.}, } @article {pmid30598776, year = {2018}, author = {Pincheira-Ulbrich, J and Hernández, CE and Saldaña, A}, title = {Consequences of swamp forest fragmentation on assemblages of vascular epiphytes and climbing plants: Evaluation of the metacommunity structure.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11785-11798}, doi = {10.1002/ece3.4635}, pmid = {30598776}, issn = {2045-7758}, abstract = {Aim: Habitat reduction in fragmented landscapes provides an opportunity to study the biogeographic patterns that drive changes in diversity in poorly studied metacommunities. In this study, colonization-extinction dynamics were indirectly evaluated through the analysis of the species-area relationship and the nestedness of vascular epiphytes and climbing plants in 30 swamp forest fragments.

Location: Coast of the Araucanía Region in Chile.

Taxon: Vascular epiphytes (16 species, mainly Pteridophytes) and climbing plants (15 species).

Methods: We used the database in Pincheira-Ulbrich et al. (New Zealand Journal of Botany, 54, 2016, 458), where 904 trees were sampled and a total abundance of 41,097 fern fronds and 3,098 climbing stems were reported. For the species-area relationship, a simple linear regression model (SLR) and two models that consider the spatial autocorrelation of species richness among fragments, generalized least squares (GLS) and simultaneous autoregressive model (SAR), were compared. For the species nestedness, the nestedness measure based on overlap and decreasing fills (NODF) and weighted nestedness metric based on overlap and decreasing fill (WNODF) indexes were used on presence-absence and abundance matrices, respectively. These matrices were sorted by area size and distance from the largest fragment and then contrasted with the probability distribution of a randomized null model based on 10,000 simulations.

Results: The results showed that the area size had a significantly positive effect on epiphyte species richness, while spatial autocorrelation played a fundamental role in explaining the richness of climbing plants. Both metacommunities had a general nestedness structure in terms of species incidence, which was determined first by area size and secondly by isolation.

Main conclusions: Our results indicate that local colonization processes determined by species' dispersal capacities could be the predominant mechanism for the spatial configuration of climbing plant species composition. On the other hand, selective extinction determined by patch size could characterize the spatial structure of epiphyte species' composition.}, } @article {pmid30598775, year = {2018}, author = {Ganser, D and Mayr, B and Albrecht, M and Knop, E}, title = {Wildflower strips enhance pollination in adjacent strawberry crops at the small scale.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11775-11784}, doi = {10.1002/ece3.4631}, pmid = {30598775}, issn = {2045-7758}, abstract = {Wildflower strips (WFS) are increasingly used to counteract the negative consequences of agricultural intensification. To date, it is poorly understood how WFS promote flower visitation and pollination services in nearby insect-pollinated crops. We therefore ask whether WFS enhance pollination service in adjacent strawberry crops, and how such an effect depends on the distance from WFS. Over 2 years, we examined the effects of experimentally sown WFS compared to grassy strips on pollination services in adjacent strawberry (Fragaria ananassa) crops across a total of 19 study sites. Moreover, we examined flower visitation, species richness and community composition of the most important insect pollinator taxa at different within-field locations varying in distance to WFS. We found increased pollination services at the edge of WFS compared to locally reduced pollination services at the center, which resulted in no significant difference in seed set between WFS and control fields. Total flower visits and species richness of pollinators were higher in WFS than in adjacent strawberry fields. Moreover, wild bee visitation was enhanced in adjacent strawberry crops near WFS compared to field centers, and intermediate at field edges near grassy strips. Our study demonstrates that diverse WFS can increase wild bee visitation and pollination services in the field edges of adjacent strawberry crops, but that overall visitation and pollination services do not increase. Moreover, our findings show that major pollinator taxa exhibit distinct responses, resulting in a shift of pollinator community composition as a function of distance to WFS with direct effects on crop pollination. Our results that WFS enhance rather than reduce crop pollination services near WFS should distract possible concerns by farmers that WFS may locally absorb rather than export crop pollinators. Considering the spatial restricted enhancement of wild bees and associated pollination services we suggest to establish WFS in the center of crop fields.}, } @article {pmid30598774, year = {2018}, author = {Kleppe, SA and Nordeide, JT and Rudolfsen, G and Figenschou, L and Larsen, B and Reiss, K and Folstad, I}, title = {No support for cryptic choice by ovarian fluid in an external fertilizer.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11763-11774}, doi = {10.1002/ece3.4628}, pmid = {30598774}, issn = {2045-7758}, abstract = {Whether the ovarian fluid (OF) represents a selective environment influencing cryptic female choice was tested using an external fertilizer experiencing intense sperm competition and large effects of OF on sperm swimming behavior-the Arctic charr (Salvelinus alpinus). We physically separated the OF from the eggs of reproductively active females and reintroduced either their own OF or fluid from another female to the eggs. The eggs were then fertilized in vitro in a replicated split-brood design with sperm from two males under synchronized sperm competition trials, while also measuring sperm velocity of the individual males in the individual OFs. We found large effects of males, but no effect of females (i.e., eggs) on paternity, determined from microsatellites. More important, we found no effect of OF treatments on the relative paternity of the two competing males in each pair. This experimental setup does not provide support for the hypothesis that OF plays an important role as medium for cryptic female choice in charr. Power analyses revealed that our sample size is large enough to detect medium-sized changes in relative paternity (medium-sized effect sizes), but not large enough to detect small changes in relative paternity. More studies are needed before a conclusion can be drawn about OF's potential influence on paternity under sperm competition-even in charr.}, } @article {pmid30598773, year = {2018}, author = {Musariri, T and Pegg, N and Muvengwi, J and Muzama, F}, title = {Differing patterns of plant spinescence affect blue duiker (Bovidae: Philantomba monticola) browsing behavior and intake rates.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11754-11762}, doi = {10.1002/ece3.4627}, pmid = {30598773}, issn = {2045-7758}, abstract = {The ways in which spines and thorns on plants affect browsing behavior and instantaneous intake rate (IIR) have been investigated for several medium and large ungulates, with most authors concluding that spines either affect the ability to obtain a full bite, or prevent the removal of twig material. We investigated how a very small ruminant, the blue duiker (Philantomba monticola; mass 5 kg), altered its feeding strategy when confronted with intact or despined branches of three species of woody plant that differed in leaf and spine size, density, and arrangement, viz. Dichrostachys cinerea africana, Vachellia (Acacia) karroo and Ziziphus mucronata. Increasing spine length and density reduced IIR (g/min), while bite size was directly related to leaf area. Bite rate and the lag time to taking the first bite did not differ among treatments. In all treatments, blue duikers cropped leaves in preference to pruning shoots. High spine density forced duikers to crop leaves at the ends of branches where spines were softer. At low spine density and on despined treatments, leaves midway along branches were preferred. Single bites (using incisors) were used preferentially in the presence of spines, with a shift to cheek bites on despined branches. We conclude that, as found with larger browsers, spines coupled with small leaf size provide the best defense against defoliation.}, } @article {pmid30598772, year = {2018}, author = {Hook, KA}, title = {No support for the sexy-sperm hypothesis in the seed beetle: Sons of monandrous females fare better in post-copulatory competition.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11742-11753}, doi = {10.1002/ece3.4626}, pmid = {30598772}, issn = {2045-7758}, abstract = {The sexy-sperm hypothesis posits that polyandrous females derive an indirect fitness benefit from multi-male mating because they increase the probability their eggs are fertilized by males whose sperm have high fertilizing efficiency, which is assumed to be heritable and conferred on their sons. However, whether this process occurs is contentious because father-to-son heritability may be constrained by the genetic architecture underlying traits important in sperm competition within certain species. Previous empirical work has revealed such genetic constraints in the seed beetle, Callosobruchus maculatus, a model system in sperm competition studies in which female multi-male mating is ubiquitous. Using the seed beetle, I tested a critical prediction of the sexy-sperm hypothesis that polyandrous females produce sons that are on average more successful under sperm competition than sons from monandrous females. Contrary to the prediction of the sexy-sperm hypothesis, I found that sons from monandrous females had significantly higher relative paternity in competitive double matings. Moreover, post hoc analyses revealed that these sons produced significantly larger ejaculates when second to mate, despite being smaller. This study is the first to provide empirical evidence for post-copulatory processes favoring monandrous sons and discusses potential explanations for the unexpected bias in paternity.}, } @article {pmid30598771, year = {2018}, author = {Zhao, L and Sun, X and Chen, Q and Yang, Y and Wang, J and Ran, J and Brauth, SE and Tang, Y and Cui, J}, title = {Males increase call frequency, not intensity, in response to noise, revealing no Lombard effect in the little torrent frog.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11733-11741}, doi = {10.1002/ece3.4625}, pmid = {30598771}, issn = {2045-7758}, abstract = {Noise is one of the main factors that can influence the processes of sound communication across a wide range of animal groups. Although the effects of ambient noise on animal communication, including anthropogenic noise, have received increasing attention, few studies have examined changes in the fine structure of acoustic signals produced by vocalizing species in constantly noisy environments. Here, we used natural recordings to determine the associations between stream noise and call parameters in the little torrent frog (Amolops torrentis). We also used playbacks of stream noise recorded in natural habitats and playbacks of white noise to examine how male vocal signals change with increasing noise levels. The results show that noise intensity has a significant effect on male call frequency, but not on call amplitude or other call characteristics. Based on this evidence, we suggest that in streamside species stream noise drives males to alter call frequency and call as loudly as possible in order to improve discriminability. These findings provide insights into the role played by ecological selection in the evolution of noise-dependent anuran vocal plasticity.}, } @article {pmid30598770, year = {2018}, author = {Hurley, LL and Rowe, M and Griffith, SC}, title = {Differential sperm-egg interactions in experimental pairings between two subspecies and their hybrids in a passerine bird.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11725-11732}, doi = {10.1002/ece3.4624}, pmid = {30598770}, issn = {2045-7758}, abstract = {Speciation research has largely overlooked reproductive barriers acting between copulation and the formation of the zygote (i.e., postmating, prezygotic [PMPZ] barriers), especially in internally fertilizing vertebrates. Nonetheless, it is becoming clear that PMPZ reproductive barriers can play a role in the formation and maintenance of species boundaries. We investigated sperm-egg interactions in the recently diverged subspecies pairs of the long-tailed finch, Poephila acuticauda acuticauda and P. a. hecki, to explore potential PMPZ barriers. Specifically, we compared the number of sperm reaching the perivitelline layer (PVL) of the ova, and hence the site of fertilization, in both intra- and inter-subspecies pairings and pairings of F1 hybrid adults with one parental subspecies. Although we found no difference in PVL sperm number among intra- and inter-subspecific pairs, a significantly lower number of sperm reached the site of fertilization in a backcross pairing. As low numbers of PVL sperm appear to be associated with low fertilization success in birds, our findings offer insight into the potential role of postcopulatory processes in limiting gene flow between the subspecies and may help explain the relatively narrow hybrid zone that exists in the wild in this species. Though further work is needed to gain a comprehensive understanding of the morphological, physiological, and molecular mechanisms underlying our results, our study supports the role of PMPZ reproductive barriers in avian speciation, even in recently diverged taxa, that may not yet be fully genetically incompatible.}, } @article {pmid30598769, year = {2018}, author = {Gomola, CE and McKay, JK and Wallenstein, MD and Wagg, C and O'Brien, MJ}, title = {Within-species trade-offs in plant-stimulated soil enzyme activity and growth, flowering, and seed size.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11717-11724}, doi = {10.1002/ece3.4623}, pmid = {30598769}, issn = {2045-7758}, abstract = {Soil microbial communities affect species demographic rates of plants. In turn, plants influence the composition and function of the soil microbiome, potentially resulting in beneficial feedbacks that alter their fitness and establishment. For example, differences in the ability to stimulate soil enzyme activity among plant lineages may affect plant growth and reproduction. We used a common garden study to test differences in plant-stimulated soil enzyme activity between lineages of the same species across developmental stages. Lineages employed different strategies whereby growth, days to flowering and seed size traded-off with plant-stimulated soil enzyme activity. Specifically, the smaller seeded lineage stimulated more enzyme activity at the early stage of development and flowered earlier while the larger seeded lineage sustained lower but consistent enzyme activity through development. We suggest that these lineages, which are both successful invaders, employ distinct strategies (a colonizer and a competitor) and differ in their influence on soil microbial activity. Synthesis. The ability to influence the soil microbial community by plants may be an important trait that trades off with growth, flowering, and seed size for promoting plant establishment, reproduction, and invasion.}, } @article {pmid30598768, year = {2018}, author = {Hu, Y and Ding, Z and Jiang, Z and Quan, Q and Guo, K and Tian, L and Hu, H and Gibson, L}, title = {Birds in the Himalayas: What drives beta diversity patterns along an elevational gradient?.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11704-11716}, doi = {10.1002/ece3.4622}, pmid = {30598768}, issn = {2045-7758}, abstract = {Beta diversity patterns along elevational gradients have become a hot topic in the study of biogeography and can help illuminate the processes structuring mountain ecosystems. Although elevational species richness patterns have been well documented, there remains much uncertainty over the causes of beta diversity patterns across elevational gradients. We conducted bird surveys and obtained high-resolution climatic data along an elevational gradient in Gyirong Valley in the central Himalayas, China, between 1,800 and 5,400 m elevation. In total, we recorded 182 bird species (including 169 breeding birds). We simulated beta diversity patterns with the mid-domain effect (MDE) null model and conducted distance-based redundancy analyses (db-RDA) to relate beta diversity to dispersal limitations, spatial constraints, habitat complexity, contemporary climate, and historical climate. Mantel tests and variation partitioning were employed to identify the magnitude of independent statistical associations of environmental factors with beta diversity. Patterns of empirical and simulated beta diversity were both hump-shaped, peaking at intermediate elevations. The db-RDA indicated that beta diversity was correlated with changes in spatially structured environmental factors, especially with contemporary climate and habitat complexity. Mantel tests and variation partitioning also suggested that climate dissimilarity was the major independent correlate of beta diversity. The random community structure and spatial constraints may also contribute to the overall hump-shaped pattern. Beta diversity of bird communities in Gyirong Valley could be explained by the combination of different factors but is mainly shaped by the spatially structured environmental factors, especially contemporary climate.}, } @article {pmid30598767, year = {2018}, author = {Liao, C and Clark, PE and DeGloria, SD}, title = {Bush encroachment dynamics and rangeland management implications in southern Ethiopia.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11694-11703}, doi = {10.1002/ece3.4621}, pmid = {30598767}, issn = {2045-7758}, abstract = {Rangelands in southern Ethiopia have been undergoing a rapid regime shift from herbaceous to woody plant dominance in the past decades, reducing indigenous plant biodiversity, altering ecosystem function, and threatening subsistence pastoralism. Despite significant rangeland management implications, quantification of spatial encroachment extent and transitional pathways that result in encroachment remain largely under-explored. This paper develops a phenology-based approach to map rangeland vegetation states in southern Ethiopia, and examines transition pathways among states using the state-and-transition model. The results indicate that nearly 80% of landscape was dominated by woody plants in 2013. While stable encroached states have been established in both high and low lands through different transition pathways between 2003 and 2013, we identified spatial locations where bush encroachment occurred rapidly. The multiplicity in the transition pathways indicates opportunities for positive transformation in the entire rangeland system in southern Ethiopia and other semi-arid regions of Africa.}, } @article {pmid30598766, year = {2018}, author = {Xiao, W and Hebblewhite, M and Robinson, H and Feng, L and Zhou, B and Mou, P and Wang, T and Ge, J}, title = {Relationships between humans and ungulate prey shape Amur tiger occurrence in a core protected area along the Sino-Russian border.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11677-11693}, doi = {10.1002/ece3.4620}, pmid = {30598766}, issn = {2045-7758}, abstract = {Large carnivore populations are globally threatened by human impacts. Better protection could benefit carnivores, co-occurring species, and the ecosystems they inhabit. The relationship between carnivores and humans, however, is not always consistent in areas of high human activities and is often mediated through the effects of humans on their ungulate prey. To test assumptions regarding how prey abundance and humans affect carnivore occurrence, density, and daily activity patterns, we assessed tiger-prey-human spatiotemporal patterns based on camera-trapping data in Hunchun Nature Reserve, a promising core area for tiger restoration in China. Our study area contained seasonally varying levels of human disturbance in summer and winter. We used N-mixture models to predict the relative abundance of ungulate prey considering human and environmental covariates. We estimated tiger spatial distribution using occupancy models and models of prey relative abundance from N-mixture models. Finally, we estimated temporal activity patterns of tigers and prey using kernel density estimates to test for temporal avoidance between tigers, prey, and humans. Our results show that human-related activities depressed the relative abundance of prey at different scales and in different ways, but across species, the relative abundance of prey directly increased tiger occupancy. Tiger occupancy was strongly positively associated with the relative abundance of sika deer in summer and winter. The crepuscular and nocturnal tigers also apparently synchronized their activity with that of wild boar and roe deer. However, tigers temporally avoided human activity without direct spatial avoidance. Our study supports the effects of humans on tigers through human impacts on prey populations. Conservation efforts may not only target human disturbance on predators, but also on prey to alleviate human-carnivore conflict.}, } @article {pmid30598765, year = {2018}, author = {Rao, M and Steinbauer, MJ and Xiang, X and Zhang, M and Mi, X and Zhang, J and Ma, K and Svenning, JC}, title = {Environmental and evolutionary drivers of diversity patterns in the tea family (Theaceae s.s.) across China.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11663-11676}, doi = {10.1002/ece3.4619}, pmid = {30598765}, issn = {2045-7758}, support = {310886//European Research Council/International ; }, abstract = {Subtropical forest is recognized as an important global vegetation type with high levels of plant species richness. However, the mechanisms underlying its diversity remain poorly understood. Here, we assessed the roles of environmental drivers and evolutionary dynamics (time-for-speciation and diversification rate) in shaping species richness patterns across China for a major subtropical plant group, the tea family (Theaceae s.s.) (145 species), at several taxonomic scales. To this end, we assessed the relationships between species richness, key environmental variables (minimum temperature of the coldest month, mean annual precipitation, soil pH), and phylogenetic assemblage structure (net related index) by using non-spatial and spatial linear models. We found that species richness is significantly related to environmental variables, especially soil pH, which is negatively related to species richness both across the whole family and within the major tribe Theeae (116 species). Family-level species richness is unrelated to phylogenetic structure, whereas species richness in tribe Theeae was related to phylogenetic structure with U-shaped relationship, a more complex relation than predicted by the time-for-speciation or diversification rate hypotheses. Overall, these results suggest that both environmental and evolutionary factors play important roles in shaping species richness patterns within this subtropical plant family across China, with the latter mainly important at fine taxonomic scales. Most surprisingly, our findings show that soils can play a key role in shaping macro-scale diversity patterns, contrary to often-stated assumptions.}, } @article {pmid30598764, year = {2018}, author = {Brown, HN and Gale, BH and Johnson, JB and Belk, MC}, title = {Testes mass in the livebearing fish Brachyrhaphis rhabdophora (Poeciliidae) varies hypoallometrically with body size but not between predation environments.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11656-11662}, doi = {10.1002/ece3.4618}, pmid = {30598764}, issn = {2045-7758}, abstract = {In this study, we considered potential causes of variation in testis size in the livebearing fish Brachyrhaphis rhabdophora. We evaluated variation in testes mass among individual males and among populations that occupy different selective environments. First, we predicted that small males should allocate more to testes mass than large males (i.e., hypoallometric pattern) based on a sperm competition argument. Second, based on life history theory and associated differences in mortality rates between populations that coexist with many fish predators and those with few predators, we predicted that males in high-predation environments should allocate more to testes mass than males in habitats with few predators. Our results showed that small males allocated proportionally more to testes mass than larger males (slope of testes mass to body mass was hypoallometric). However, there was no effect of predator environment on testes mass independent of body size differences. In this system, size-specific patterns of reproductive allocation in males (hypoallometry) differ from that seen in females (hyperallometry). Allocation to testes mass may respond to differences in mortality rate through selection on body size.}, } @article {pmid30598763, year = {2018}, author = {Axelsson, EP and Senior, JK}, title = {The extended consequences of genetic conductivity: Mating distance affects community phenotypes in Norway spruce.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11645-11655}, doi = {10.1002/ece3.4616}, pmid = {30598763}, issn = {2045-7758}, abstract = {Anthropogenic landscape-level alterations such as habitat fragmentation and long distance translocation of genetic material are currently altering the genetic connectivity and structure of forest tree populations globally. As the susceptibility of individual trees to dependent organisms is often genetically determined, it is possible that these genetic changes may extend beyond individuals to affect associated communities. To test this, we examined how variation in crossing distance among the progeny of 18 controlled crosses of Norway spruce (Picea abies) populations occurring across central Sweden affected chemical defense, and subsequently, a small community of galling Adelges aphids infecting planted trees at two common garden trails. Although crossing distance did not influence growth, vitality or reproduction in the studied population, it did influence the expression of one candidate defensive chemical compound, apigenin, which was found in higher concentrations within outcrossed trees. We also show that this variation in apigenin induced by crossing distance correlated with susceptibility to one member of the galling community but not the other. Furthermore, the effect of crossing distance on galling communities and the general susceptibility of Norway spruce to infection also varied with environment. Specifically, in the more benign environment, inbred trees suffered greater gall infection than outcrossed trees, which is contrary to general predictions that the effects of inbreeding should be more pronounced in harsher environments. These findings suggest that the effects of variation in crossing distance in forest trees can extend beyond the individual to influence whole communities.}, } @article {pmid30598762, year = {2018}, author = {Roney, NE and Oomen, RA and Knutsen, H and Olsen, EM and Hutchings, JA}, title = {Fine-scale population differences in Atlantic cod reproductive success: A potential mechanism for ecological speciation in a marine fish.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11634-11644}, doi = {10.1002/ece3.4615}, pmid = {30598762}, issn = {2045-7758}, abstract = {Successful resource-management and conservation outcomes ideally depend on matching the spatial scales of population demography, local adaptation, and threat mitigation. For marine fish with high dispersal capabilities, this remains a fundamental challenge. Based on daily parentage assignments of more than 4,000 offspring, we document fine-scaled temporal differences in individual reproductive success for two spatially adjacent (<10 km) populations of a broadcast-spawning marine fish. Distinguished by differences in genetics and life history, Atlantic cod (Gadus morhua) from inner- and outer-fjord populations were allowed to compete for mating and reproductive opportunities. After accounting for phenotypic variability in several traits, reproductive success of outer-fjord cod was significantly lower than that of inner-fjord cod. This finding, given that genomically different cod ecotypes inhabit inner- and outer-fjord waters, raises the intriguing hypothesis that the populations might be diverging because of ecological speciation. Individual reproductive success, skewed within both sexes (more so among males), was positively affected by body size, which also influenced the timing of reproduction, larger individuals spawning later among females but earlier among males. Our work suggests that spatial mismatches between management and biological units exist in marine fishes and that studies of reproductive interactions between putative populations or ecotypes can provide an informative basis on which determination of the scale of local adaptation can be ascertained.}, } @article {pmid30598761, year = {2018}, author = {Mayer, M and Ullmann, W and Sunde, P and Fischer, C and Blaum, N}, title = {Habitat selection by the European hare in arable landscapes: The importance of small-scale habitat structure for conservation.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11619-11633}, doi = {10.1002/ece3.4613}, pmid = {30598761}, issn = {2045-7758}, abstract = {Agricultural land-use practices have intensified over the last decades, leading to population declines of various farmland species, including the European hare (Lepus europaeus). In many European countries, arable fields dominate agricultural landscapes. Compared to pastures, arable land is highly variable, resulting in a large spatial variation of food and cover for wildlife over the course of the year, which potentially affects habitat selection by hares. Here, we investigated within-home-range habitat selection by hares in arable areas in Denmark and Germany to identify habitat requirements for their conservation. We hypothesized that hare habitat selection would depend on local habitat structure, that is, vegetation height, but also on agricultural field size, vegetation type, and proximity to field edges. Active hares generally selected for short vegetation (1-25 cm) and avoided higher vegetation and bare ground, especially when fields were comparatively larger. Vegetation >50 cm potentially restricts hares from entering parts of their home range and does not provide good forage, the latter also being the case on bare ground. The vegetation type was important for habitat selection by inactive hares, with fabaceae, fallow, and maize being selected for, potentially providing both cover and forage. Our results indicate that patches of shorter vegetation could improve the forage quality and habitat accessibility for hares, especially in areas with large monocultures. Thus, policymakers should aim to increase areas with short vegetation throughout the year. Further, permanent set-asides, like fallow and wildflower areas, would provide year-round cover for inactive hares. Finally, the reduction in field sizes would increase the density of field margins, and farming different crop types within small areas could improve the habitat for hares and other farmland species.}, } @article {pmid30598760, year = {2018}, author = {Zhao, Z and Wei, J and Zhang, K and Li, H and Wei, S and Pan, X and Huang, W and Zhu, M and Zhang, R}, title = {Asymmetric response of different functional insect groups to low-grazing pressure in Eurasian steppe in Ningxia.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11609-11618}, doi = {10.1002/ece3.4611}, pmid = {30598760}, issn = {2045-7758}, abstract = {In recent years, the continued loss and fragmentation of steppe has caused decreased ecosystem functions and species losses in insect diversity. In the 2000s, the Chinese government developed a series of national projects, such as the construction of enclosures, to conserve natural ecosystems, including steppe. However, the effects of these enclosures on steppe arthropod community are largely unknown. In the present study, we selected enclosed and low-grazing regions at eight National Grassland Fixed Monitoring Stations to examine the compositional differences in four insect functional groups and their associated ecological functions. The results showed that diversity significantly differed between the enclosed and low-grazing regions, with the number of insect families being significantly higher in enclosed regions than in regions with low-grazing pressure. The responses of the insect community to steppe management also varied among the four groups (herbivores, predators, parasitoids, and pollinators). The abundances of herbivores, predators, and parasitoids were higher in enclosed regions than in low-grazing regions, while there was no significant difference in pollinators. Additionally, there were no significant differences in the predator/prey ratio between enclosed regions and low-grazing regions in any of the steppe types. The parasitic wasp/prey ratio was higher in enclosed regions than in low-grazing regions in meadow steppe and typical steppe, while there were no significant differences between the enclosed and low-grazing regions in desert steppe and steppe desert. Herbivores were observed to benefit much more from enclosures than predators, parasitoids, and pollinators. Therefore, we recommend low-grazing should be considered in steppe conservation, which could conserve biodiversity and achieve biocontrol functions of arthropod community.}, } @article {pmid30598759, year = {2018}, author = {Grendelmeier, A and Arlettaz, R and Pasinelli, G}, title = {Numerical response of mammalian carnivores to rodents affects bird reproduction in temperate forests: A case of apparent competition?.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11596-11608}, doi = {10.1002/ece3.4608}, pmid = {30598759}, issn = {2045-7758}, abstract = {Resource pulses such as mast seeding in temperate forests may affect interspecific interactions over multiple trophic levels and link different seed and nonseed consumers directly via predation or indirectly via shared predators. However, the nature and strength of interactions among species remain unknown for most resource pulse-driven ecosystems. We considered five hypotheses concerning the influence of resource pulses on the interactions between rodents, predators, and bird reproduction with data from northern Switzerland collected between 2010 and 2015. In high-rodent-abundance-years (HRAYs), wood warbler (Phylloscopus sibilatrix) nest survival was lower than in low-rodent-abundance-years, but rodents were not important nest predators, in contrast to rodent-hunting predators. The higher proportion of nests predated by rodent-hunting predators and their increased occurrence in HRAYs suggests a rodent-mediated aggregative numerical response of rodent-hunting predators, which incidentally prey on the wood warbler's ground nests. There was no evidence that rodent-hunting predators responded behaviorally by switching prey. Lastly, nest losses caused by nonrodent-hunting predators were not related to rodent abundance. We show that wood warblers and rodents are linked via shared predators in a manner consistent with apparent competition, where an increase of one species coincides with the decrease of another species mediated by shared predators. Mast seeding frequency and annual seed production appear to have increased over the past century, which may result in more frequent HRAYs and generally higher peaking rodent populations. The associated increase in the magnitude of apparent competition may thus at least to some extent explain the wood warbler's decline in much of Western Europe.}, } @article {pmid30598758, year = {2018}, author = {Felicitas, AC and Hervé, BDB and Ekesi, S and Akutse, KS and Djuideu, CTCL and Meupia, MJ and Babalola, OO}, title = {Consequences of shade management on the taxonomic patterns and functional diversity of termites (Blattodea: Termitidae) in cocoa agroforestry systems.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11582-11595}, doi = {10.1002/ece3.4607}, pmid = {30598758}, issn = {2045-7758}, abstract = {Termites have gained importance as major pests in cocoa agroforests. Proper identification of termite species and knowledge on their functional diversity are the first steps in developing environmentally compatible management strategies. We tested the hypothesis that patterns of termite species richness in different cocoa agroforests is related to responses by termite functional groups to changes in shade management. We compared termite assemblages under five cocoa agroforestry systems in Cameroon to assess the impact of shade on termite taxonomic and functional group diversity. Sampling was done using a modified standardized transect method. Two 30 × 30 m quadrates each divided into three transects were laid in four farms at each site. Termites sampled were identified and grouped according to habitats, functional groups, and feeding habits. Sixty-nine termite species in 33 genera and five subfamilies under two families were sampled. Termitidae was the most dominant family and Rhinotermitidae the least dominant with few species. Termite species richness decreased significantly from the heavy shaded cocoa agroforests (44 species) to the full sun (11 species). Functional group pattern differed significantly in all the cocoa agroforests and within each agroforestry system and dominated by wood and litter feeder species. Many species belonging to this group were responsible to most damages on cocoa trees. Both the richness of termite pests and marketable yield followed a quadratic curve and were found to be lowest and highest in plots with shade cover above 40%. The simulated optimal shade levels for low termite infestations and marketable yield overlapped between 45% and 65% indicating that cocoa agroforestry systems with around 55% shade cover may be optimal to balance termite infestations and marketable yield. Shade maintenance in cocoa agroforests is valuable in reducing termite pest species and conserving soil feeding termites which provide beneficial ecosystem services.}, } @article {pmid30598757, year = {2018}, author = {Roy, J and Bonneville, JM and Saccone, P and Ibanez, S and Albert, CH and Boleda, M and Gueguen, M and Ohlmann, M and Rioux, D and Clément, JC and Lavergne, S and Geremia, RA}, title = {Differences in the fungal communities nursed by two genetic groups of the alpine cushion plant, Silene acaulis.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11568-11581}, doi = {10.1002/ece3.4606}, pmid = {30598757}, issn = {2045-7758}, abstract = {Foundation plants shape the composition of local biotic communities and abiotic environments, but the impact of a plant's intraspecific variations on these processes is poorly understood. We examined these links in the alpine cushion moss campion (Silene acaulis) on two neighboring mountain ranges in the French Alps. Genotyping of cushion plants revealed two genetic clusters matching known subspecies. The exscapa subspecies was found on both limestone and granite, while the longiscapa one was only found on limestone. Even on similar limestone bedrock, cushion soils from the two S. acaulis subspecies deeply differed in their impact on soil abiotic conditions. They further strikingly differed from each other and from the surrounding bare soils in fungal community composition. Plant genotype variations accounted for a large part of the fungal composition variability in cushion soils, even when considering geography or soil chemistry, and particularly for the dominant molecular operational taxonomic units (MOTUs). Both saprophytic and biotrophic fungal taxa were related to the MOTUs recurrently associated with a single plant genetic cluster. Moreover, the putative phytopathogens were abundant, and within the same genus (Cladosporium) or species (Pyrenopeziza brassicae), MOTUs showing specificity for each plant subspecies were found. Our study highlights the combined influences of bedrock and plant genotype on fungal recruitment into cushion soils and suggests the coexistence of two mechanisms, an indirect selection resulting from the colonization of an engineered soil by free-living saprobes and a direct selection resulting from direct plant-fungi interactions.}, } @article {pmid30598756, year = {2018}, author = {Carilla, J and Halloy, S and Cuello, S and Grau, A and Malizia, A and Cuesta, F}, title = {Vegetation trends over eleven years on mountain summits in NW Argentina.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11554-11567}, doi = {10.1002/ece3.4602}, pmid = {30598756}, issn = {2045-7758}, abstract = {As global climate change leads to warmer and dryer conditions in the central Andes, alpine plant communities are forced to upward displacements following their climatic niche. Species range shifts are predicted to have major impacts on alpine communities by reshuffling species composition and abundances. Using a standardized protocol, we surveyed alpine plant communities in permanent plots on four high Andean summits in NW Argentina, which range from 4,040 to 4,740 m a.s.l. After a baseline survey in 2006-2008, we resurvey the same plots in 2012, and again in 2017. We found a significant decrease in plant cover, species richness, and diversity across the elevation gradient in the three censuses and a strong decrease in soil temperature along the elevation gradient. We found a high plant community turnover (37%-49%) among censuses, differentiating according to summits and aspects; major changes of community turnover were observed in the lowest summit (49%) and on the northern (47%) and western (46%) aspects. Temporal patterns in community changes were represented by increases in plant cover in the highest summit, in species richness in the lower summit, and in diversity (Shannon index) in the four summits, over time, together with increase in small herbs and non-tussock grasses. We suggest that the observed trend in plant community dynamics responds to short-term temperature and precipitation variability, which is influenced by El Niño Southern Oscillation (ENSO), and due to time lags in plant community response, it may take much longer than one decade for the observed trends to become stables and statistically significant. Our study provides an important foundation for documenting more profound changes in these subtropical alpine plant communities as global climate change continues.}, } @article {pmid30598755, year = {2018}, author = {Kroeger, SB and Blumstein, DT and Armitage, KB and Reid, JM and Martin, JGA}, title = {Cumulative reproductive costs on current reproduction in a wild polytocous mammal.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11543-11553}, doi = {10.1002/ece3.4597}, pmid = {30598755}, issn = {2045-7758}, abstract = {The cumulative cost of reproduction hypothesis predicts that reproductive costs accumulate over an individual's reproductive life span. While short-term costs have been extensively explored, the prevalence of cumulative long-term costs and the circumstances under which such costs occur alongside or instead of short-term costs, are far from clear. Indeed, few studies have simultaneously tested for both short-term and cumulative long-term reproductive costs in natural populations. Even in mammals, comparatively little is known about cumulative effects of previous reproduction, especially in species with high variation in offspring numbers, where costs could vary among successful reproductive events. Here, we quantify effects of previous short-term and cumulative long-term reproduction on current reproduction probability and litter size in wild female yellow-bellied marmots (Marmota flaviventer) and test how these effects vary with age and between two contrasting environments. We provide evidence for cumulative long-term effects: females that had both reproduced frequently and weaned large litters on average in previous years had decreased current reproduction probability. We found no evidence for short-term reproductive costs between reproductive bouts. However, females weaned larger litters when they had weaned larger litters on average in previous years and had lower current reproduction probability when their previous reproductive success was low. Together these results suggest that, alongside persistent among-individual variation, long-term reproductive history affects current reproductive success.}, } @article {pmid30598754, year = {2018}, author = {Richardson, WC and Whitaker, DR and Sant, KP and Barney, NS and Call, RS and Roundy, BA and Aanderud, ZT and Madsen, MD}, title = {Use of auto-germ to model germination timing in the sagebrush-steppe.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11533-11542}, doi = {10.1002/ece3.4591}, pmid = {30598754}, issn = {2045-7758}, abstract = {Germination timing has a strong influence on direct seeding efforts, and therefore is a closely tracked demographic stage in a wide variety of wildland and agricultural settings. Predictive seed germination models, based on soil moisture and temperature data in the seed zone are an efficient method of estimating germination timing. We utilized Visual Basic for Applications (VBA) to create Auto-Germ, which is an Excel workbook that allows a user to estimate field germination timing based on wet-thermal accumulation models and field temperature and soil moisture data. To demonstrate the capabilities of Auto-Germ, we calculated various germination indices and modeled germination timing for 11 different species, across 6 years, and 10 Artemisia-steppe sites in the Great Basin of North America to identify the planting date required for 50% or more of the simulated population to germinate in spring (1 March or later), which is when conditions are predicted to be more conducive for plant establishment. Both between and within the species, germination models indicated that there was high temporal and spatial variability in the planting date required for spring germination to occur. However, some general trends were identified, with species falling roughly into three categories, where seeds could be planted on average in either fall (Artemisia tridentata ssp. wyomingensis and Leymus cinereus), early winter (Festuca idahoensis, Poa secunda, Elymus lanceolatus, Elymus elymoides, and Linum lewisii), or mid-winter (Achillea millefolium, Elymus wawawaiensis, and Pseudoroegneria spicata) and still not run the risk of germination during winter. These predictions made through Auto-Germ demonstrate that fall may not be an optimal time period for sowing seeds for most non-dormant species if the desired goal is to have seeds germinate in spring.}, } @article {pmid30598753, year = {2018}, author = {Farallo, VR and Wier, R and Miles, DB}, title = {The Bogert effect revisited: Salamander regulatory behaviors are differently constrained by time and space.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11522-11532}, doi = {10.1002/ece3.4590}, pmid = {30598753}, issn = {2045-7758}, abstract = {The use of behavior to buffer extreme environmental variation is expected to enable species to (a) extend the breadth of environments they inhabit beyond that predicted from climatic data and (b) diminish the negative effects of broad scale and chronic disturbances such as climate change. The term Bogert effect refers to behavioral compensation entailing microhabitat selection to maintain performance across a gradient of environmental conditions resulting in evolutionary inertia of physiological traits. Here, we compare microhabitats used by plethodontid salamanders distributed along an elevational gradient to determine whether there is behavioral compensation that buffers them from deleterious temperatures and moisture levels. Overall, salamanders preferred cooler and more mesic environments and occupied microhabitats that maintained constant moisture conditions at both high- and low-elevation sites. Our results suggest that salamanders use microhabitats to regulate temperature and moisture levels, which is consistent with the Bogert effect. Maintenance of more moist conditions may help buffer these species from rising temperatures but only in suitable high-elevation environments that are likely to disappear over the next century. We conclude that behavioral regulation of temperature and moisture is a potential mechanism for the Bogert effect in plethodontid salamanders.}, } @article {pmid30598752, year = {2018}, author = {György, Z and Tóth, EG and Incze, N and Molnár, B and Höhn, M}, title = {Intercontinental migration pattern and genetic differentiation of arctic-alpine Rhodiola rosea L.: A chloroplast DNA survey.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11508-11521}, doi = {10.1002/ece3.4589}, pmid = {30598752}, issn = {2045-7758}, abstract = {Our study describes genetic lineages and historical biogeography of Rhodiola rosea a widely distributed arctic-alpine perennial species of the Northern Hemisphere based on sequence analysis of six chloroplast regions. Specimens of 44 localities from the Northern Hemisphere have been sequenced and compared with those available in the GenBank. Our results support the migration of the species into Europe via the Central Asian highland corridor, reaching the European Alpine System (EAS) and also the western European edge, the British Isles. The EAS proved to be an important center of genetic diversity, especially the region of the Eastern Alps and the Dolomites where signs of glacial refugia was observed. Apart from those of the EAS, a common lineage was detected along the Atlantic coast from the British Isles toward Scandinavia as well as Iceland and the eastern parts of North America. Accordingly, the British Isles represent a main link between the northern Atlantic and southern EAS lineages.}, } @article {pmid30598751, year = {2018}, author = {Fox, CW and Ritchey, JP and Paine, CET}, title = {Patterns of authorship in ecology and evolution: First, last, and corresponding authorship vary with gender and geography.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11492-11507}, doi = {10.1002/ece3.4584}, pmid = {30598751}, issn = {2045-7758}, abstract = {The position of an author on the byline of a paper affects the inferences readers make about their contributions to the research. We examine gender differences in authorship in the ecology literature using two datasets: submissions to six journals between 2010 and 2015 (regardless of whether they were accepted), and manuscripts published by 151 journals between 2009 and 2015. Women were less likely to be last (i.e., "senior") authors (averaging ~23% across journals, years, and datasets) and sole authors (~24%), but more likely to be first author (~38%), relative to their overall frequency of authorship (~31%). However, the proportion of women in all authorship roles, except sole authorship, has increased year-on-year. Women were less likely to be authors on papers with male last authors, and all-male papers were more abundant than expected given the overall gender ratio. Women were equally well represented on papers published in higher versus lower impact factor journals at all authorship positions. Female first authors were less likely to serve as corresponding author of their papers; this difference increased with the degree of gender inequality in the author's home country, but did not depend on the gender of the last author. First authors from non-English-speaking countries were less likely to serve as corresponding author of their papers, especially if the last author was from an English-speaking country. That women more often delegate corresponding authorship to one of their coauthors may increase the likelihood that readers undervalue their role in the research by shifting credit for their contributions to coauthors. We suggest that author contribution statements be more universally adopted and that these statements declare how and/or why the corresponding author was selected for this role.}, } @article {pmid30598750, year = {2018}, author = {Zanatta, F and Vanderpoorten, A and Hedenäs, L and Johansson, V and Patiño, J and Lönnell, N and Hylander, K}, title = {Under which humidity conditions are moss spores released? A comparison between species with perfect and specialized peristomes.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11484-11491}, doi = {10.1002/ece3.4579}, pmid = {30598750}, issn = {2045-7758}, abstract = {Dispersal is a fundamental biological process that can be divided into three phases: release, transportation, and deposition. Determining the mechanisms of diaspore release is of prime importance to understand under which climatic conditions and at which frequency diaspores are released and transported. In mosses, wherein spore dispersal takes place through the hygroscopic movements of the peristome, the factors enhancing spore release has received little attention. Here, we determine the levels of relative humidity (RH) at which peristome movements are induced, contrasting the response of species with perfect (fully developed) and specialized (reduced) peristomes. All nine investigated species with perfect peristomes displayed a xerochastic behavior, initiating a closing movement from around 50%-65% RH upon increasing humidity and an opening movement from around 90% RH upon drying. Five of the seven species with specialized peristomes exhibited a hygrochastic behavior, initiating an opening movement under increasing RH (from about 80%) and a closing movement upon drying (from about 90%). These differences between species with hygrochastic and xerochastic peristomes suggest that spore dispersal does not randomly occur regardless of the prevailing climate conditions, which can impact their dispersal distances. In species with xerochastic peristomes, the release of spores under decreasing RH can be interpreted as an adaptive mechanism to disperse spores under optimal conditions for long-distance wind dispersal. In species with hygrochastic peristomes, conversely, the release of spores under wet conditions, which decreases their wind long-distance dispersal capacities, might be seen as a safe-site strategy, forcing spores to land in appropriate (micro-) habitats where their survival is favored. Significant variations were observed in the RH thresholds triggering peristome movements among species, especially in those with hygrochastic peristomes, raising the question of what mechanisms are responsible for such differences.}, } @article {pmid30598749, year = {2018}, author = {Wang, S and Wang, TT and Tang, JP and Wang, L and Yang, Y and Lin, HJ and Chang, HY and Zhou, XA and Li, X and Wang, M}, title = {Longitudinal variation in fish prey utilization, trophic guilds, and indicator species along a large subtropical river, China.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11467-11483}, doi = {10.1002/ece3.4577}, pmid = {30598749}, issn = {2045-7758}, abstract = {Due to the heterogeneous distribution of resources along large rivers, understanding prey utilization by basin-scale fish assemblages remains a challenge, and thus, recognizing regional fish trophic guilds and indicator species is important. We analyzed the stomach contents of 96 fish species along the subtropical East River in China and identified 8 prey items (29 subcategories). Site-specific differences in fish diet composition (DC) revealed longitudinal shifts in utilized prey taxa, from upstream lotic to downstream semi-lentic items, and these were characterized by a decrease in the proportions of epilithic diatoms and aquatic insect larvae (Ephemeroptera and Chironomidae) accompanied by an increase in bivalves (Corbicula and Limnoperna), shrimps and fishes, and organic sediments. The relative prey consumption weighted by fish abundance and biomass indicated that decreasing insect consumption and increasing detritus consumption were two fundamental vectors governing fish-centered feeding pathways. Seventeen prey-oriented fish guilds that were clustered based on DC matrix determined the spatial variation in the fish trophic structure. The cumulative presence of (a) upstream guilds reliant on insects and epiphytes, (b) midstream guilds reliant on hydrophytes, molluscs, and nekton, and (c) downstream guilds reliant on detritus, annelids, and plankton resulted in a longitudinal increase in guild richness, but this continuity was interrupted near the industrialized estuary. The most abundant 28 fish species across the guilds were selected as trophic indicator species; their spatial distribution significantly (p < 0.05) explained >80% of the environmental and prey variables identified. These species signified the availability of predator-prey links in distinct habitats and the key environmental factors supporting these links. With a high contribution (>51%) of exotic species, an increase in detritivores downstream distinguishes the subtropical East River from temperate rivers. Particularly, in the disturbed lower reaches, the dominance of detritivores prevailed over the predicted increase in other feeding groups (e.g., omnivores and carnivores).}, } @article {pmid30598748, year = {2018}, author = {Milleret, C and Ordiz, A and Chapron, G and Andreassen, HP and Kindberg, J and Månsson, J and Tallian, A and Wabakken, P and Wikenros, C and Zimmermann, B and Swenson, JE and Sand, H}, title = {Habitat segregation between brown bears and gray wolves in a human-dominated landscape.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11450-11466}, doi = {10.1002/ece3.4572}, pmid = {30598748}, issn = {2045-7758}, abstract = {Identifying how sympatric species belonging to the same guild coexist is a major question of community ecology and conservation. Habitat segregation between two species might help reduce the effects of interspecific competition and apex predators are of special interest in this context, because their interactions can have consequences for lower trophic levels. However, habitat segregation between sympatric large carnivores has seldom been studied. Based on monitoring of 53 brown bears (Ursus arctos) and seven sympatric adult gray wolves (Canis lupus) equipped with GPS collars in Sweden, we analyzed the degree of interspecific segregation in habitat selection within their home ranges in both late winter and spring, when their diets overlap the most. We used the K-select method, a multivariate approach that relies on the concept of ecological niche, and randomization methods to quantify habitat segregation between bears and wolves. Habitat segregation between bears and wolves was greater than expected by chance. Wolves tended to select for moose occurrence, young forests, and rugged terrain more than bears, which likely reflects the different requirements of an omnivore (bear) and an obligate carnivore (wolf). However, both species generally avoided human-related habitats during daytime. Disentangling the mechanisms that can drive interspecific interactions at different spatial scales is essential for understanding how sympatric large carnivores occur and coexist in human-dominated landscapes, and how coexistence may affect lower trophic levels. The individual variation in habitat selection detected in our study may be a relevant mechanism to overcome intraguild competition and facilitate coexistence.}, } @article {pmid30598747, year = {2018}, author = {Lerche-Jørgensen, M and Korner-Nievergelt, F and Tøttrup, AP and Willemoes, M and Thorup, K}, title = {Early returning long-distance migrant males do pay a survival cost.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11434-11449}, doi = {10.1002/ece3.4569}, pmid = {30598747}, issn = {2045-7758}, abstract = {Timing of return to the breeding area presumably optimizes breeding output in migrants. How timing affects the other components of fitness - survival, has been comparatively little studied. Returning too early in spring is expected to be associated with high mortality in insectivorous migrants when weather conditions are still unsuitable. Yet, males in particular arrive early to get access to the best territories which have been suggested to cause arrival before it is optimal for their survival. For the outward migration in autumn, timing is presumably less directly associated with reproduction and fitness and how it might affect survival is not well understood. We use data of eight songbird species ringed across Denmark to investigate how timing of return migration in spring and departure migration in autumn close to the breeding areas affects survival for short- and long-distance migrants. Further, we compare survival optimum to the timing of males and females at a stopover site in Denmark in three sexually dimorphic, protandric species. We find a clear relationship between return migration and survival which differs between short- and long-distance migrants: Survival decreases with date for short-distance migrants and a bell-shaped relationship, with low survival for earliest and latest individuals, for long-distance migrants. In protandric species, the majority of males return before survival is optimal, whereas females on average return close to the survival optimum. The pattern of survival in relation to autumn timing is less clear, although a similar bell-shaped relationship is suggested for long-distance migrants. Our findings support the predicted mortality consequences of too early return to the breeding grounds and also that selection for early return in males leads to suboptimal migration timing regarding survival.}, } @article {pmid30598746, year = {2018}, author = {Tanner, JE and Althaus, F and Sorokin, SJ and Williams, A}, title = {Benthic biogeographic patterns in the southern Australian deep sea: Do historical museum records accord with recent systematic, but spatially limited, survey data?.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11423-11433}, doi = {10.1002/ece3.4565}, pmid = {30598746}, issn = {2045-7758}, abstract = {Aim: To document biogeographic patterns in the deepwater benthic epifauna and demersal fishes of southern Australia, and determine whether museum records and systematic survey data provide matching results.

Location: Southern Australian (32-44oS) continental slope (200-3,000 m deep).

Taxon: Marine benthic fauna (Arthropoda, Bryozoa, Cnidaria, Echinodermata, Mollusca, Porifera, Sipuncula, and fishes).

Methods: All available electronic records of fauna from the above taxa and ≥200 m depth off the southern Australian coastline, regardless of organism size, were collated from Australian museums and checked for geographic and taxonomic consistency. These records were then split into 40 geographic segments of roughly equal numbers, with each segment then treated as a sample in multivariate analyses of assemblage composition. Data from a recent (2015) systematic beam trawl survey along five north-south transects in the central Great Australian Bight were also included for comparison.

Main conclusions: The systematic survey data grouped with the associated geographic segments despite differences in sampling technique (single gear compared to multiple gears), with subsequent differences in taxonomic biases, and the use of a 25 mm mesh, which would undersample some smaller organisms present in the museum data. Thus, the museum data and the survey data provided the same results for the central Great Australian Bight at the level of the whole assemblage. The main biogeographic break occurred off southeastern Tasmania, with a second substantial break occurring at around the border between New South Wales and Victoria. This indicates the potential for unused museum data to describe biogeographic patterns over regional spatial scales, especially in the deep sea where the expense of collecting new data is relatively high.}, } @article {pmid30598745, year = {2018}, author = {Bruce, SA and Wright, JJ}, title = {Estimates of gene flow and dispersal in wild riverine Brook Trout (Salvelinus fontinalis) populations reveal ongoing migration and introgression from stocked fish.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11410-11422}, doi = {10.1002/ece3.4556}, pmid = {30598745}, issn = {2045-7758}, abstract = {As anthropogenic impacts accelerate changes to landscapes across the globe, understanding how genetic population structure is influenced by habitat features and dispersal is key to preserving evolutionary potential at the species level. Furthermore, knowledge of these interactions is essential to identifying potential constraints on local adaptation and for the development of effective management strategies. We examined these issues in Brook Trout (Salvelinus fontinalis) populations residing in the Upper Hudson River watershed of New York State by investigating the spatial genetic structure of over 350 fish collected from 14 different sampling locations encompassing three river systems. Population genetic analyses of microsatellite data suggest that fish in the area exhibit varying degrees of introgression from nearby State-directed supplementation activities. Levels of introgression in these populations correlate with water-way distance to stocking sites, although genetic population structure at the level of individual tributaries as well as their larger, parent river systems is also detectable and is dictated by migration and influenced by habitat connectivity. These findings represent a significant contribution to the current literature surrounding Brook Trout migration and dispersal, especially as it relates to larger interconnected systems. This work also suggests that stocking activities may have far-reaching consequences that are not directly limited to the immediate area where stocking occurs. The framework and data presented here may aid in the development of other local aquatic species-focused conservation plans that incorporate molecular tools to answer complex questions regarding diversity mapping, and genetically important conservation units.}, } @article {pmid30598744, year = {2018}, author = {Aguilar-Puntriano, C and Avila, LJ and De la Riva, I and Johnson, L and Morando, M and Troncoso-Palacios, J and Wood, PL and Sites, JW}, title = {The shadow of the past: Convergence of young and old South American desert lizards as measured by head shape traits.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11399-11409}, doi = {10.1002/ece3.4548}, pmid = {30598744}, issn = {2045-7758}, abstract = {Convergence is a pervasive phenomenon in the Tree of Life, and evolution of similar phenotypes sharing the same environmental conditions is expected in phylogenetically closely related species. In contrast, contingent factors are probably more influential in shaping phenotypic diversity for distantly related taxa. Here, we test putative convergent evolution of lizard head morphologies among relatively closely related desert dwelling Liolaemus species, and the very distantly related Ctenoblepharys adspersa. We estimated a multilocus time-calibrated phylogeny of 57 species of South American liolaemus lizards, based on seven molecular markers. We collected head shape data for 468 specimens, and used three phylogenetic comparative methods (SURFACE, CONVEVOL, and WHEATSHEAF index) to test for and estimate the strength of convergence. We found strong evidence for convergence among Pacific desert lizard C. adspersa, Liolaemus audivetulatus, Liolaemus insolitus, Liolaemus poconchilensis, Liolaemus stolzmanni, and a candidate species (Liolaemus "Moquegua"). Our results suggest that, despite the long divergence and phylogenetic distance of C. adspersa with respect to convergent Liolaemus species, natural selection was probably more important than historical contingency in shaping phenotypic evolution in these desert lizards.}, } @article {pmid30598743, year = {2018}, author = {Torres, CW and Tonione, MA and Ramírez, SR and Sapp, JR and Tsutsui, ND}, title = {Genetic and chemical divergence among host races of a socially parasitic ant.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11385-11398}, doi = {10.1002/ece3.4547}, pmid = {30598743}, issn = {2045-7758}, abstract = {Host-parasite associations facilitate the action of reciprocal selection and can drive rapid evolutionary change. When multiple host species are available to a single parasite, parallel specialization on different hosts may promote the action of diversifying natural selection and divergence via host race formation. Here, we examine a population of the kidnapper ant (Polyergus mexicanus) that is an obligate social parasite of three sympatric ant species: Formica accreta, F. argentea, and F. subaenescens (formerly F. fusca). Behavioral and ecological observations of P. mexicanus have shown that individual colonies parasitize only one species of host and that new Polyergus queens maintain host fidelity when establishing new colonies. To successfully adapt to a particular host, Polyergus ants may mimic or camouflage themselves with the species-specific chemical cues (cuticular hydrocarbons) that their hosts use to ascertain colony membership. To investigate the extent of host specialization, we collected both genetic and chemical data from P. mexicanus that parasitize each of the three different Formica species in sympatry. We show that host-associated genetic structure exists for both maternally inherited mitochondrial DNA data and biparentally inherited microsatellite markers. We also show that P. mexicanus can be distinguished by chemical profile according to host due to partial matching with their host. Our results support the hypothesis that host race formation is occurring among lineages of P. mexicanus that use different Formica hosts. Thus, this system may represent a promising model for illuminating the early steps of divergence, accumulation of reproductive isolation, and speciation.}, } @article {pmid30598742, year = {2018}, author = {Xiong, G and Zhang, A and Fan, D and Ge, J and Yang, D and Xie, Z and Zhang, W}, title = {Functional coordination between leaf traits and biomass allocation and growth of four herbaceous species in a newly established reservoir riparian ecosystem in China.}, journal = {Ecology and evolution}, volume = {8}, number = {23}, pages = {11372-11384}, doi = {10.1002/ece3.4494}, pmid = {30598742}, issn = {2045-7758}, abstract = {The flood-dry-flood cycle in the reservoir riparian zone (RRZ) of the Three Gorges Dam has dramatically altered the riparian ecosystem structure and composition. Previous field studies have shown that leaf traits varied greatly and were restricted to the lower-investment and faster-return end of the global leaf spectrum, which are typical characteristics of fast-growing species. However, it is unclear as to the mechanism underpinning the growth potential of these species and how it will respond to soil nutrient availability and temperature. Here, we linked the plant functional traits of four representative dominant C4 herbaceous species (Setaria viridis, Echinochloa crusgalli, Cynodon dactylon and Hemarthria altissima) to their relative growth rates (RGR) under ambient and elevated temperatures, with different nitrogen and phosphorus levels, to explore the potential mechanism of species growth in the newly established reservoir riparian ecosystem in the Three Gorges Reservoir Area, China. We grew seedlings of these species in four open-top chambers, with three levels of nutrient supplies under two temperature gradients (ambient temperature and an elevated temperature of 4°C). We found that the responses of the RGR and plant traits to soil N and P supply levels and temperature varied considerably among studied species. E. crusgalli displayed the lowest RGR associated with relatively low specific leaf area (SLA), leaf nitrogen content (LN), stem mass ratio (SMR), and high leaf mass ratio (LMR) and was less affected by soil N and P supply levels and temperature. C. dactylon and H. altissima showed the highest RGR compared to the other two species grown at the substrate of N = 0.4 mg/g, P = 0.2 mg/g at ambient air temperature, associated with a relatively high SMR, low LMR and low plant carbon content (PCC). However, the RGR advantage of the two species was diminished at elevated temperatures, while S. viridis showed the highest RGR compared to the other species. Across all datasets, the RGR had no association with the leaf area ratio (LAR) and SLA. The RGR also showed no significant relationships with the LN and leaf phosphorus content (LP). On the other hand, the RGR was captured adequately by the SMR, which can therefore be considered as a powerful functional marker of species' functioning in this newly established reservoir riparian ecosystem. Our study provides some insight into the underlying mechanisms of species growth in reservoir riparian ecosystems.}, } @article {pmid30598549, year = {2019}, author = {Morris, JA and Kemp, JP and Youlten, SE and Laurent, L and Logan, JG and Chai, RC and Vulpescu, NA and Forgetta, V and Kleinman, A and Mohanty, ST and Sergio, CM and Quinn, J and Nguyen-Yamamoto, L and Luco, AL and Vijay, J and Simon, MM and Pramatarova, A and Medina-Gomez, C and Trajanoska, K and Ghirardello, EJ and Butterfield, NC and Curry, KF and Leitch, VD and Sparkes, PC and Adoum, AT and Mannan, NS and Komla-Ebri, DSK and Pollard, AS and Dewhurst, HF and Hassall, TAD and Beltejar, MG and , and Adams, DJ and Vaillancourt, SM and Kaptoge, S and Baldock, P and Cooper, C and Reeve, J and Ntzani, EE and Evangelou, E and Ohlsson, C and Karasik, D and Rivadeneira, F and Kiel, DP and Tobias, JH and Gregson, CL and Harvey, NC and Grundberg, E and Goltzman, D and Adams, DJ and Lelliott, CJ and Hinds, DA and Ackert-Bicknell, CL and Hsu, YH and Maurano, MT and Croucher, PI and Williams, GR and Bassett, JHD and Evans, DM and Richards, JB}, title = {An atlas of genetic influences on osteoporosis in humans and mice.}, journal = {Nature genetics}, volume = {51}, number = {2}, pages = {258-266}, doi = {10.1038/s41588-018-0302-x}, pmid = {30598549}, issn = {1546-1718}, support = {R35 GM119703/GM/NIGMS NIH HHS/United States ; R21 AR060981/AR/NIAMS NIH HHS/United States ; R01 AR072199/AR/NIAMS NIH HHS/United States ; R01 AR041398/AR/NIAMS NIH HHS/United States ; R01 AR063702/AR/NIAMS NIH HHS/United States ; }, abstract = {Osteoporosis is a common aging-related disease diagnosed primarily using bone mineral density (BMD). We assessed genetic determinants of BMD as estimated by heel quantitative ultrasound in 426,824 individuals, identifying 518 genome-wide significant loci (301 novel), explaining 20% of its variance. We identified 13 bone fracture loci, all associated with estimated BMD (eBMD), in ~1.2 million individuals. We then identified target genes enriched for genes known to influence bone density and strength (maximum odds ratio (OR) = 58, P = 1 × 10-75) from cell-specific features, including chromatin conformation and accessible chromatin sites. We next performed rapid-throughput skeletal phenotyping of 126 knockout mice with disruptions in predicted target genes and found an increased abnormal skeletal phenotype frequency compared to 526 unselected lines (P < 0.0001). In-depth analysis of one gene, DAAM2, showed a disproportionate decrease in bone strength relative to mineralization. This genetic atlas provides evidence linking associated SNPs to causal genes, offers new insight into osteoporosis pathophysiology, and highlights opportunities for drug development.}, } @article {pmid30598548, year = {2019}, author = {Park, SL and Buzzai, A and Rautela, J and Hor, JL and Hochheiser, K and Effern, M and McBain, N and Wagner, T and Edwards, J and McConville, R and Wilmott, JS and Scolyer, RA and Tüting, T and Palendria, U and Gyorki, D and Mueller, SN and Huntington, ND and Bedoui, S and Hölzel, M and Mackay, LK and Waithman, J and Gebhardt, T}, title = {Tissue-resident memory CD8+ T cells promote melanoma-immune equilibrium in skin.}, journal = {Nature}, volume = {565}, number = {7739}, pages = {366-371}, doi = {10.1038/s41586-018-0812-9}, pmid = {30598548}, issn = {1476-4687}, abstract = {The immune system can suppress tumour development both by eliminating malignant cells and by preventing the outgrowth and spread of cancer cells that resist eradication1. Clinical and experimental data suggest that the latter mode of control-termed cancer-immune equilibrium1-can be maintained for prolonged periods of time, possibly up to several decades2-4. Although cancers most frequently originate in epithelial layers, the nature and spatiotemporal dynamics of immune responses that maintain cancer-immune equilibrium in these tissue compartments remain unclear. Here, using a mouse model of transplantable cutaneous melanoma5, we show that tissue-resident memory CD8+ T cells (TRM cells) promote a durable melanoma-immune equilibrium that is confined to the epidermal layer of the skin. A proportion of mice (~40%) transplanted with melanoma cells remained free of macroscopic skin lesions long after epicutaneous inoculation, and generation of tumour-specific epidermal CD69+ CD103+ TRM cells correlated with this spontaneous disease control. By contrast, mice deficient in TRM formation were more susceptible to tumour development. Despite being tumour-free at the macroscopic level, mice frequently harboured melanoma cells in the epidermal layer of the skin long after inoculation, and intravital imaging revealed that these cells were dynamically surveyed by TRM cells. Consistent with their role in melanoma surveillance, tumour-specific TRM cells that were generated before melanoma inoculation conferred profound protection from tumour development independently of recirculating T cells. Finally, depletion of TRM cells triggered tumour outgrowth in a proportion (~20%) of mice with occult melanomas, demonstrating that TRM cells can actively suppress cancer progression. Our results show that TRM cells have a fundamental role in the surveillance of subclinical melanomas in the skin by maintaining cancer-immune equilibrium. As such, they provide strong impetus for exploring these cells as targets of future anticancer immunotherapies.}, } @article {pmid30598547, year = {2019}, author = {Sakai, N and Hanawa, T and Zhang, Y and Higuchi, AE and Ohashi, S and Oya, Y and Yamamoto, S}, title = {A warped disk around an infant protostar.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {206-208}, doi = {10.1038/s41586-018-0819-2}, pmid = {30598547}, issn = {1476-4687}, abstract = {Recent exoplanet studies have revealed that the orbital planes of planets are not always aligned with one another or with the equatorial plane of the central star. The misalignment has been ascribed to gravitational scattering by giant planets and/or companion stars1-3 or to fly-bys in stellar cluster environments4. Alternatively, the misalignment could be natal: that is, such planets were born in a warped protostellar disk5,6. Warped disk structures have been reported in some transition disks and protoplanetary disks7,8, but not in the earlier stages of protostar evolution, although such a possibility is suggested by outflow morphology9,10. Here we report millimetre-wavelength dust continuum observations of the young embedded protostar IRAS 04368+2557 in the protostellar core L1527 at a distance11 of 137 parsecs; the protostar's disk is almost edge-on12-16. The inner and outer parts of the disk have slightly different orbital planes, connected at 40 to 60 astronomical units from the star, but the disk has point symmetry with respect to the position of the protostar. We interpret it as a warped disk that is rotationally supported. Because there is no evidence for a companion source17,18, the warped structure must be due to either anisotropic accretion of gas with different rotational axes, or misalignment of the rotation axis of the disk with the magnetic field direction.}, } @article {pmid30598546, year = {2019}, author = {Yang, G and Zhou, R and Zhou, Q and Guo, X and Yan, C and Ke, M and Lei, J and Shi, Y}, title = {Structural basis of Notch recognition by human γ-secretase.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {192-197}, doi = {10.1038/s41586-018-0813-8}, pmid = {30598546}, issn = {1476-4687}, abstract = {Aberrant cleavage of Notch by γ-secretase leads to several types of cancer, but how γ-secretase recognizes its substrate remains unknown. Here we report the cryo-electron microscopy structure of human γ-secretase in complex with a Notch fragment at a resolution of 2.7 Å. The transmembrane helix of Notch is surrounded by three transmembrane domains of PS1, and the carboxyl-terminal β-strand of the Notch fragment forms a β-sheet with two substrate-induced β-strands of PS1 on the intracellular side. Formation of the hybrid β-sheet is essential for substrate cleavage, which occurs at the carboxyl-terminal end of the Notch transmembrane helix. PS1 undergoes pronounced conformational rearrangement upon substrate binding. These features reveal the structural basis of Notch recognition and have implications for the recruitment of the amyloid precursor protein by γ-secretase.}, } @article {pmid30598529, year = {2019}, author = {Blundell, JR and Schwartz, K and Francois, D and Fisher, DS and Sherlock, G and Levy, SF}, title = {The dynamics of adaptive genetic diversity during the early stages of clonal evolution.}, journal = {Nature ecology & evolution}, volume = {3}, number = {2}, pages = {293-301}, doi = {10.1038/s41559-018-0758-1}, pmid = {30598529}, issn = {2397-334X}, abstract = {The dynamics of genetic diversity in large clonally evolving cell populations are poorly understood, despite having implications for the treatment of cancer and microbial infections. Here, we combine barcode lineage tracking, sequencing of adaptive clones and mathematical modelling of mutational dynamics to understand adaptive diversity changes during experimental evolution of Saccharomyces cerevisiae under nitrogen and carbon limitation. We find that, despite differences in beneficial mutational mechanisms and fitness effects, early adaptive genetic diversity increases predictably, driven by the expansion of many single-mutant lineages. However, a crash in adaptive diversity follows, caused by highly fit double-mutant 'jackpot' clones that are fed from exponentially growing single mutants, a process closely related to the classic Luria-Delbrück experiment. The diversity crash is likely to be a general feature of asexual evolution with clonal interference; however, both its timing and magnitude are stochastic and depend on the population size, the distribution of beneficial fitness effects and patterns of epistasis.}, } @article {pmid30598528, year = {2019}, author = {Ma, A and Lu, X and Gray, C and Raybould, A and Tamaddoni-Nezhad, A and Woodward, G and Bohan, DA}, title = {Ecological networks reveal resilience of agro-ecosystems to changes in farming management.}, journal = {Nature ecology & evolution}, volume = {3}, number = {2}, pages = {260-264}, doi = {10.1038/s41559-018-0757-2}, pmid = {30598528}, issn = {2397-334X}, abstract = {Sustainable management of ecosystems and growth in agricultural productivity is at the heart of the United Nations' Sustainable Development Goals for 2030. New management regimes could revolutionize agricultural production, but require an evaluation of the risks and opportunities. Replacing existing conventional weed management with genetically modified, herbicide-tolerant (GMHT) crops, for example, might reduce herbicide applications and increase crop yields, but remains controversial owing to concerns about potential impacts on biodiversity. Until now, such new regimes have been assessed at the species or assemblage level, whereas higher-level ecological network effects remain largely unconsidered. Here, we conduct a large-scale network analysis of invertebrate communities across 502 UK farm sites to GMHT management in different crop types. We find that network-level properties were overwhelmingly shaped by crop type, whereas network structure and robustness were apparently unaltered by GMHT management. This suggests that taxon-specific effects reported previously did not escalate into higher-level systemic structural change in the wider agricultural ecosystem. Our study highlights current limitations of autecological assessments of effect in agriculture in which species interactions and potential compensatory effects are overlooked. We advocate adopting the more holistic system-level evaluations that we explore here, which complement existing assessments for meeting our future agricultural needs.}, } @article {pmid30598455, year = {2019}, author = {Arbel, H and Basu, S and Fisher, WW and Hammonds, AS and Wan, KH and Park, S and Weiszmann, R and Booth, BW and Keranen, SV and Henriquez, C and Shams Solari, O and Bickel, PJ and Biggin, MD and Celniker, SE and Brown, JB}, title = {Exploiting regulatory heterogeneity to systematically identify enhancers with high accuracy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {900-908}, doi = {10.1073/pnas.1808833115}, pmid = {30598455}, issn = {1091-6490}, abstract = {Identifying functional enhancer elements in metazoan systems is a major challenge. Large-scale validation of enhancers predicted by ENCODE reveal false-positive rates of at least 70%. We used the pregrastrula-patterning network of Drosophila melanogaster to demonstrate that loss in accuracy in held-out data results from heterogeneity of functional signatures in enhancer elements. We show that at least two classes of enhancers are active during early Drosophila embryogenesis and that by focusing on a single, relatively homogeneous class of elements, greater than 98% prediction accuracy can be achieved in a balanced, completely held-out test set. The class of well-predicted elements is composed predominantly of enhancers driving multistage segmentation patterns, which we designate segmentation driving enhancers (SDE). Prediction is driven by the DNA occupancy of early developmental transcription factors, with almost no additional power derived from histone modifications. We further show that improved accuracy is not a property of a particular prediction method: after conditioning on the SDE set, naïve Bayes and logistic regression perform as well as more sophisticated tools. Applying this method to a genome-wide scan, we predict 1,640 SDEs that cover 1.6% of the genome. An analysis of 32 SDEs using whole-mount embryonic imaging of stably integrated reporter constructs chosen throughout our prediction rank-list showed >90% drove expression patterns. We achieved 86.7% precision on a genome-wide scan, with an estimated recall of at least 98%, indicating high accuracy and completeness in annotating this class of functional elements.}, } @article {pmid30598454, year = {2019}, author = {Yi, J and Jung, J and Hong, SW and Lee, JY and Han, D and Kim, KS and Sprent, J and Surh, CD}, title = {Unregulated antigen-presenting cell activation by T cells breaks self tolerance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {1007-1016}, doi = {10.1073/pnas.1818624116}, pmid = {30598454}, issn = {1091-6490}, abstract = {T cells proliferate vigorously following acute depletion of CD4+ Foxp3+ T regulatory cells [natural Tregs (nTregs)] and also when naive T cells are transferred to syngeneic, nTreg-deficient Rag1-/- hosts. Here, using mice raised in an antigen-free (AF) environment, we show that proliferation in these two situations is directed to self ligands rather than food or commensal antigens. In both situations, the absence of nTregs elevates B7 expression on host dendritic cells (DCs) and enables a small subset of naive CD4 T cells with high self affinity to respond overtly to host DCs: bidirectional T/DC interaction ensues, leading to progressive DC activation and reciprocal strong proliferation of T cells accompanied by peripheral Treg (pTreg) formation. Likewise, high-affinity CD4 T cells proliferate vigorously and form pTregs when cultured with autologous DCs in vitro in the absence of nTregs: this anti-self response is MHCII/peptide dependent and elicited by the raised level of B7 on cultured DCs. The data support a model in which self tolerance is imposed via modulation of CD28 signaling and explains the pathological effects of superagonistic CD28 antibodies.}, } @article {pmid30598453, year = {2019}, author = {Piscotta, FJ and Jeffrey, PD and Link, AJ}, title = {ParST is a widespread toxin-antitoxin module that targets nucleotide metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {826-834}, doi = {10.1073/pnas.1814633116}, pmid = {30598453}, issn = {1091-6490}, support = {R01 GM107036/GM/NIGMS NIH HHS/United States ; }, abstract = {Toxin-antitoxin (TA) systems interfere with essential cellular processes and are implicated in bacterial lifestyle adaptations such as persistence and the biofilm formation. Here, we present structural, biochemical, and functional data on an uncharacterized TA system, the COG5654-COG5642 pair. Bioinformatic analysis showed that this TA pair is found in 2,942 of the 16,286 distinct bacterial species in the RefSeq database. We solved a structure of the toxin bound to a fragment of the antitoxin to 1.50 Å. This structure suggested that the toxin is a mono-ADP-ribosyltransferase (mART). The toxin specifically modifies phosphoribosyl pyrophosphate synthetase (Prs), an essential enzyme in nucleotide biosynthesis conserved in all organisms. We propose renaming the toxin ParT for Prs ADP-ribosylating toxin and ParS for the cognate antitoxin. ParT is a unique example of an intracellular protein mART in bacteria and is the smallest known mART. This work demonstrates that TA systems can induce bacteriostasis through interference with nucleotide biosynthesis.}, } @article {pmid30598452, year = {2019}, author = {Mayle, R and Langston, L and Molloy, KR and Zhang, D and Chait, BT and O'Donnell, ME}, title = {Mcm10 has potent strand-annealing activity and limits translocase-mediated fork regression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {798-803}, doi = {10.1073/pnas.1819107116}, pmid = {30598452}, issn = {1091-6490}, support = {P41 GM103314/GM/NIGMS NIH HHS/United States ; R01 GM115809/GM/NIGMS NIH HHS/United States ; T32 CA009673/CA/NCI NIH HHS/United States ; }, abstract = {The 11-subunit eukaryotic replicative helicase CMG (Cdc45, Mcm2-7, GINS) tightly binds Mcm10, an essential replication protein in all eukaryotes. Here we show that Mcm10 has a potent strand-annealing activity both alone and in complex with CMG. CMG-Mcm10 unwinds and then reanneals single strands soon after they have been unwound in vitro. Given the DNA damage and replisome instability associated with loss of Mcm10 function, we examined the effect of Mcm10 on fork regression. Fork regression requires the unwinding and pairing of newly synthesized strands, performed by a specialized class of ATP-dependent DNA translocases. We show here that Mcm10 inhibits fork regression by the well-known fork reversal enzyme SMARCAL1. We propose that Mcm10 inhibits the unwinding of nascent strands to prevent fork regression at normal unperturbed replication forks, either by binding the fork junction to form a block to SMARCAL1 or by reannealing unwound nascent strands to their parental template. Analysis of the CMG-Mcm10 complex by cross-linking mass spectrometry reveals Mcm10 interacts with six CMG subunits, with the DNA-binding region of Mcm10 on the N-face of CMG. This position on CMG places Mcm10 at the fork junction, consistent with a role in regulating fork regression.}, } @article {pmid30598451, year = {2019}, author = {Bichler, M and Fux, V and Goeree, JK}, title = {Designing combinatorial exchanges for the reallocation of resource rights.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {786-791}, doi = {10.1073/pnas.1802123116}, pmid = {30598451}, issn = {1091-6490}, abstract = {We describe the design and implementation of a combinatorial exchange for trading catch shares in New South Wales, Australia. The exchange ended a decades-long political debate by providing a market-based response to a major policy problem faced by fisheries worldwide: the reallocation of catch shares in cap-and-trade programs designed to prevent overfishing. The exchange was conducted over the Internet to lower participation costs and allowed for all-or-nothing orders to avoid fragmented share portfolios. A subsidy was distributed endogenously to facilitate the transfer of shares from inactive to active fishers. Finally, prices were linear and anonymous to ensure that sellers of identical packages received the same payments. These features were crucial to mitigate economic distortions from introducing catch shares and to gain broad acceptance of the program. However, they led to computationally challenging allocation and pricing problems. The exchange operated from May to July 2017 and effectively reallocated shares from inactive fishers to those who needed them most: 86% of active fishers' bids were matched and their share deficits were reduced by 95% in high-priority share classes. Similar reallocation problems arise in fisheries with catch-share systems worldwide as well as in other cap-and-trade systems for resource rights, e.g., water and pollution rights. The implemented exchange illustrates how computational optimization and market design can provide policy tools, able to solve complex policy problems considered intractable only a few years ago.}, } @article {pmid30598450, year = {2019}, author = {Park, DE and Cheng, J and Berrios, C and Montero, J and Cortés-Cros, M and Ferretti, S and Arora, R and Tillgren, ML and Gokhale, PC and DeCaprio, JA}, title = {Dual inhibition of MDM2 and MDM4 in virus-positive Merkel cell carcinoma enhances the p53 response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {1027-1032}, doi = {10.1073/pnas.1818798116}, pmid = {30598450}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Merkel cell polyomavirus (MCV) contributes to approximately 80% of all Merkel cell carcinomas (MCCs), a highly aggressive neuroendocrine carcinoma of the skin. MCV-positive MCC expresses small T antigen (ST) and a truncated form of large T antigen (LT) and usually contains wild-type p53 (TP53) and RB (RB1). In contrast, virus-negative MCC contains inactivating mutations in TP53 and RB1. While the MCV-truncated LT can bind and inhibit RB, it does not bind p53. We report here that MCV LT binds to RB, leading to increased levels of ARF, an inhibitor of MDM2, and activation of p53. However, coexpression of ST reduced p53 activation. MCV ST recruits the MYC homologue MYCL (L-Myc) to the EP400 chromatin remodeler complex and transactivates specific target genes. We observed that depletion of EP400 in MCV-positive MCC cell lines led to increased p53 target gene expression. We suspected that the MCV ST-MYCL-EP400 complex could functionally inactivate p53, but the underlying mechanism was not known. Integrated ChIP and RNA-sequencing analysis following EP400 depletion identified MDM2 as well as CK1α, an activator of MDM4, as target genes of the ST-MYCL-EP400 complex. In addition, MCV-positive MCC cells expressed high levels of MDM4. Combining MDM2 inhibitors with lenalidomide targeting CK1α or an MDM4 inhibitor caused synergistic activation of p53, leading to an apoptotic response in MCV-positive MCC cells and MCC-derived xenografts in mice. These results support dual targeting of MDM2 and MDM4 in virus-positive MCC and other p53 wild-type tumors.}, } @article {pmid30598449, year = {2018}, author = {Chen, N and Juric, I and Cosgrove, EJ and Bowman, R and Fitzpatrick, JW and Schoech, SJ and Clark, AG and Coop, G}, title = {Allele frequency dynamics in a pedigreed natural population.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1813852116}, pmid = {30598449}, issn = {1091-6490}, abstract = {A central goal of population genetics is to understand how genetic drift, natural selection, and gene flow shape allele frequencies through time. However, the actual processes underlying these changes-variation in individual survival, reproductive success, and movement-are often difficult to quantify. Fully understanding these processes requires the population pedigree, the set of relationships among all individuals in the population through time. Here, we use extensive pedigree and genomic information from a long-studied natural population of Florida Scrub-Jays (Aphelocoma coerulescens) to directly characterize the relative roles of different evolutionary processes in shaping patterns of genetic variation through time. We performed gene dropping simulations to estimate individual genetic contributions to the population and model drift on the known pedigree. We found that observed allele frequency changes are generally well predicted by accounting for the different genetic contributions of founders. Our results show that the genetic contribution of recent immigrants is substantial, with some large allele frequency shifts that otherwise may have been attributed to selection actually due to gene flow. We identified a few SNPs under directional short-term selection after appropriately accounting for gene flow. Using models that account for changes in population size, we partitioned the proportion of variance in allele frequency change through time. Observed allele frequency changes are primarily due to variation in survival and reproductive success, with gene flow making a smaller contribution. This study provides one of the most complete descriptions of short-term evolutionary change in allele frequencies in a natural population to date.}, } @article {pmid30598448, year = {2019}, author = {Kawazura, Y and Barnes, M and Schekochihin, AA}, title = {Thermal disequilibration of ions and electrons by collisionless plasma turbulence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {771-776}, doi = {10.1073/pnas.1812491116}, pmid = {30598448}, issn = {1091-6490}, abstract = {Does overall thermal equilibrium exist between ions and electrons in a weakly collisional, magnetized, turbulent plasma? And, if not, how is thermal energy partitioned between ions and electrons? This is a fundamental question in plasma physics, the answer to which is also crucial for predicting the properties of far-distant astronomical objects such as accretion disks around black holes. In the context of disks, this question was posed nearly two decades ago and has since generated a sizeable literature. Here we provide the answer for the case in which energy is injected into the plasma via Alfvénic turbulence: Collisionless turbulent heating typically acts to disequilibrate the ion and electron temperatures. Numerical simulations using a hybrid fluid-gyrokinetic model indicate that the ion-electron heating-rate ratio is an increasing function of the thermal-to-magnetic energy ratio, [Formula: see text]: It ranges from [Formula: see text] at [Formula: see text] to at least 30 for [Formula: see text] This energy partition is approximately insensitive to the ion-to-electron temperature ratio [Formula: see text] Thus, in the absence of other equilibrating mechanisms, a collisionless plasma system heated via Alfvénic turbulence will tend toward a nonequilibrium state in which one of the species is significantly hotter than the other, i.e., hotter ions at high [Formula: see text] and hotter electrons at low [Formula: see text] Spectra of electromagnetic fields and the ion distribution function in 5D phase space exhibit an interesting new magnetically dominated regime at high [Formula: see text] and a tendency for the ion heating to be mediated by nonlinear phase mixing ("entropy cascade") when [Formula: see text] and by linear phase mixing (Landau damping) when [Formula: see text].}, } @article {pmid30598447, year = {2019}, author = {Reisert, J and Reingruber, J}, title = {Ca2+-activated Cl- current ensures robust and reliable signal amplification in vertebrate olfactory receptor neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {1053-1058}, doi = {10.1073/pnas.1816371116}, pmid = {30598447}, issn = {1091-6490}, support = {R01 DC016647/DC/NIDCD NIH HHS/United States ; }, abstract = {Activation of most primary sensory neurons results in transduction currents that are carried by cations. One notable exception is the vertebrate olfactory receptor neuron (ORN), where the transduction current is carried largely by the anion [Formula: see text] However, it remains unclear why ORNs use an anionic current for signal amplification. We have sought to provide clarification on this topic by studying the so far neglected dynamics of [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] in the small space of olfactory cilia during an odorant response. Using computational modeling and simulations we compared the outcomes of signal amplification based on either [Formula: see text] or [Formula: see text] currents. We found that amplification produced by [Formula: see text] influx instead of a [Formula: see text] efflux is problematic for several reasons: First, the [Formula: see text] current amplitude varies greatly, depending on mucosal ion concentration changes. Second, a [Formula: see text] current leads to a large increase in the ciliary [Formula: see text] concentration during an odorant response. This increase inhibits and even reverses [Formula: see text] clearance by [Formula: see text] exchange, which is essential for response termination. Finally, a [Formula: see text] current increases the ciliary osmotic pressure, which could cause swelling to damage the cilia. By contrast, a transduction pathway based on [Formula: see text] efflux circumvents these problems and renders the odorant response robust and reliable.}, } @article {pmid30598446, year = {2019}, author = {Papkou, A and Guzella, T and Yang, W and Koepper, S and Pees, B and Schalkowski, R and Barg, MC and Rosenstiel, PC and Teotónio, H and Schulenburg, H}, title = {The genomic basis of Red Queen dynamics during rapid reciprocal host-pathogen coevolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {923-928}, doi = {10.1073/pnas.1810402116}, pmid = {30598446}, issn = {1091-6490}, abstract = {Red Queen dynamics, involving coevolutionary interactions between species, are ubiquitous, shaping the evolution of diverse biological systems. To date, information on the underlying selection dynamics and the involved genome regions is mainly available for bacteria-phage systems or only one of the antagonists of a eukaryotic host-pathogen interaction. We add to our understanding of these important coevolutionary interactions using an experimental host-pathogen model, which includes the nematode Caenorhabditis elegans and its pathogen Bacillus thuringiensis We combined experimental evolution with time-shift experiments, in which a focal host or pathogen is tested against a coevolved antagonist from the past, present, or future, followed by genomic analysis. We show that (i) coevolution occurs rapidly within few generations, (ii) temporal coadaptation at the phenotypic level is found in parallel across replicate populations, consistent with antagonistic frequency-dependent selection, (iii) genomic changes in the pathogen match the phenotypic pattern and include copy number variations of a toxin-encoding plasmid, and (iv) host genomic changes do not match the phenotypic pattern and likely involve selective responses at more than one locus. By exploring the dynamics of coevolution at the phenotypic and genomic level for both host and pathogen simultaneously, our findings demonstrate a more complex model of the Red Queen, consisting of distinct selective processes acting on the two antagonists during rapid and reciprocal coadaptation.}, } @article {pmid30598445, year = {2019}, author = {Hipp, L and Beer, J and Kuchler, O and Reisser, M and Sinske, D and Michaelis, J and Gebhardt, JCM and Knöll, B}, title = {Single-molecule imaging of the transcription factor SRF reveals prolonged chromatin-binding kinetics upon cell stimulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {880-889}, doi = {10.1073/pnas.1812734116}, pmid = {30598445}, issn = {1091-6490}, abstract = {Serum response factor (SRF) mediates immediate early gene (IEG) and cytoskeletal gene expression programs in almost any cell type. So far, SRF transcriptional dynamics have not been investigated at single-molecule resolution. We provide a study of single Halo-tagged SRF molecules in fibroblasts and primary neurons. In both cell types, individual binding events of SRF molecules segregated into three chromatin residence time regimes, short, intermediate, and long binding, indicating a cell type-independent SRF property. The chromatin residence time of the long bound fraction was up to 1 min in quiescent cells and significantly increased upon stimulation. Stimulation also enhanced the long bound SRF fraction at specific timepoints (20 and 60 min) in both cell types. These peaks correlated with activation of the SRF cofactors MRTF-A and MRTF-B (myocardin-related transcription factors). Interference with signaling pathways and cofactors demonstrated modulation of SRF chromatin occupancy by actin signaling, MAP kinases, and MRTFs.}, } @article {pmid30598444, year = {2019}, author = {Furuse, Y}, title = {Analysis of research intensity on infectious disease by disease burden reveals which infectious diseases are neglected by researchers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {478-483}, doi = {10.1073/pnas.1814484116}, pmid = {30598444}, issn = {1091-6490}, abstract = {Infectious diseases are associated with considerable morbidity and mortality worldwide. Although human, financial, substantial, and time resources are limited, it is unknown whether such resources are used effectively in research to manage diseases. The correlation between the disability-adjusted life years to represent disease burden and number of publications as a surrogate for research activity was investigated to measure burden-adjusted research intensity for 52 infectious diseases at global and country levels. There was significantly low research intensity for paratyphoid fever and high intensity for influenza, HIV/acquired immunodeficiency syndrome, hepatitis C, and tuberculosis considering their disease burden. We identified the infectious diseases that have received the most attention from researchers and those that have been relatively disregarded. Interestingly, not all so-called neglected tropical diseases were subject to low burden-adjusted research intensity. Analysis of the intensity of infectious disease research at a country level revealed characteristic patterns. These findings provided a basis for further discussion of the more appropriate allocation of resources for research into infectious diseases.}, } @article {pmid30598443, year = {2019}, author = {West-Eberhard, MJ}, title = {Nutrition, the visceral immune system, and the evolutionary origins of pathogenic obesity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {723-731}, doi = {10.1073/pnas.1809046116}, pmid = {30598443}, issn = {1091-6490}, abstract = {The global obesity epidemic is the subject of an immense, diversely specialized research effort. An evolutionary analysis reveals connections among disparate findings, starting with two well-documented facts: Obesity-associated illnesses (e.g., type-2 diabetes and cardiovascular disease), are especially common in: (i) adults with abdominal obesity, especially enlargement of visceral adipose tissue (VAT), a tissue with important immune functions; and (ii) individuals with poor fetal nutrition whose nutritional input increases later in life. I hypothesize that selection favored the evolution of increased lifelong investment in VAT in individuals likely to suffer lifelong malnutrition because of its importance in fighting intraabdominal infections. Then, when increased nutrition violates the adaptive fetal prediction of lifelong nutritional deficit, preferential VAT investment could contribute to abdominal obesity and chronic inflammatory disease. VAT prioritization may help explain several patterns of nutrition-related disease: the paradoxical increase of chronic disease with increased food availability in recently urbanized and migrant populations; correlations between poor fetal nutrition, improved childhood (catch-up) growth, and adult metabolic syndrome; and survival differences between children with marasmus and kwashiorkor malnutrition. Fats and sugars can aggravate chronic inflammation via effects on intestinal bacteria regulating gut permeability to visceral pathogens. The extremes in a nutrition-sensitive trade-off between visceral (immune-function) vs. subcutaneous (body shape) adiposity may have been favored by selection in highly stratified premedicine societies. Altered adipose allocation in populations with long histories of social stratification and malnutrition may be the result of genetic accommodation of developmental responses to poor maternal/fetal conditions, increasing their vulnerability to inflammatory disease.}, } @article {pmid30598442, year = {2019}, author = {Zhu, Y and Mohapatra, S and Weisshaar, JC}, title = {Rigidification of the Escherichia coli cytoplasm by the human antimicrobial peptide LL-37 revealed by superresolution fluorescence microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {1017-1026}, doi = {10.1073/pnas.1814924116}, pmid = {30598442}, issn = {1091-6490}, support = {R01 GM094510/GM/NIGMS NIH HHS/United States ; }, abstract = {Superresolution, single-particle tracking reveals effects of the cationic antimicrobial peptide LL-37 on the Escherichia coli cytoplasm. Seconds after LL-37 penetrates the cytoplasmic membrane, the chromosomal DNA becomes rigidified on a length scale of ∼30 nm, evidenced by the loss of jiggling motion of specific DNA markers. The diffusive motion of a subset of ribosomes is also frozen. The mean diffusion coefficients of the DNA-binding protein HU and the nonendogenous protein Kaede decrease twofold. Roughly 108 LL-37 copies flood the cell (mean concentration ∼90 mM). Much of the LL-37 remains bound within the cell after extensive rinsing with fresh growth medium. Growth never recovers. The results suggest that the high concentration of adsorbed polycationic peptides forms a dense network of noncovalent, electrostatic linkages within the chromosomal DNA and among 70S-polysomes. The bacterial cytoplasm comprises a concentrated collection of biopolymers that are predominantly polyanionic (e.g., DNA, ribosomes, RNA, and most globular proteins). In normal cells, this provides a kind of electrostatic lubrication, enabling facile diffusion despite high biopolymer volume fraction. However, this same polyanionic nature renders the cytoplasm susceptible to massive adsorption of polycationic agents once penetration of the membranes occurs. If this phenomenon proves widespread across cationic agents and bacterial species, it will help explain why resistance to antimicrobial peptides develops only slowly. The results suggest two design criteria for polycationic peptides that efficiently kill gram-negative bacteria: facile penetration of the outer membrane and the ability to alter the cytoplasm by electrostatically linking double-stranded DNA and 70S-polysomes.}, } @article {pmid30598441, year = {2019}, author = {Van der Stocken, T and Carroll, D and Menemenlis, D and Simard, M and Koedam, N}, title = {Global-scale dispersal and connectivity in mangroves.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {915-922}, doi = {10.1073/pnas.1812470116}, pmid = {30598441}, issn = {1091-6490}, abstract = {Dispersal provides a key mechanism for geographical range shifts in response to changing environmental conditions. For mangroves, which are highly susceptible to climate change, the spatial scale of dispersal remains largely unknown. Here we use a high-resolution, eddy- and tide-resolving numerical ocean model to simulate mangrove propagule dispersal across the global ocean and generate connectivity matrices between mangrove habitats using a range of floating periods. We find high rates of along-coast transport and transoceanic dispersal across the Atlantic, Pacific, and Indian Oceans. No connectivity is observed between populations on either side of the American and African continents. Archipelagos, such as the Galapagos and those found in Polynesia, Micronesia, and Melanesia, act as critical stepping-stones for dispersal across the Pacific Ocean. Direct and reciprocal dispersal routes across the Indian Ocean via the South Equatorial Current and seasonally reversing monsoon currents, respectively, allow connectivity between western Indian Ocean and Indo-West Pacific sites. We demonstrate the isolation of the Hawaii Islands and help explain the presence of mangroves on the latitudinal outlier Bermuda. Finally, we find that dispersal distance and connectivity are highly sensitive to the minimum and maximum floating periods. We anticipate that our findings will guide future research agendas to quantify biophysical factors that determine mangrove dispersal and connectivity, including the influence of ocean surface water properties on metabolic processes and buoyancy behavior, which may determine the potential of viably reaching a suitable habitat. Ultimately, this will lead to a better understanding of global mangrove species distributions and their response to changing climate conditions.}, } @article {pmid30598440, year = {2019}, author = {Rangel, MA and Shi, Y}, title = {Early patterns of skill acquisition and immigrants' specialization in STEM careers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {484-489}, doi = {10.1073/pnas.1812041116}, pmid = {30598440}, issn = {1091-6490}, abstract = {We provide empirical evidence of immigrants' specialization in skill acquisition well before entering the US labor market. Nationally representative datasets enable studying the academic trajectories of immigrant children, with a focus on high-school course-taking patterns and college major choice. Immigrant children accumulate skills in ways that reinforce comparative advantages in nonlanguage intensive skills such as mathematics and science, and this contributes to their growing numbers in science, technology, engineering, and math (STEM) careers. These results are compatible with well-established models of skill formation that emphasize dynamic complementarities of investments in learning.}, } @article {pmid30598439, year = {2019}, author = {Rennella, E and Morgan, GJ and Kelly, JW and Kay, LE}, title = {Role of domain interactions in the aggregation of full-length immunoglobulin light chains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {854-863}, doi = {10.1073/pnas.1817538116}, pmid = {30598439}, issn = {1091-6490}, support = {R01 DK046335/DK/NIDDK NIH HHS/United States ; }, abstract = {Amyloid light-chain (LC) amyloidosis is a protein misfolding disease in which the aggregation of an overexpressed antibody LC from a clonal plasma cell leads to organ toxicity and patient death if left untreated. While the overall dimeric architecture of LC molecules is established, with each LC composed of variable (VL) and constant (CL) domains, the relative contributions of LC domain-domain interfaces and intrinsic domain stabilities to protection against LC aggregation are not well understood. To address these topics we have engineered a number of domain-destabilized LC mutants and used solution NMR spectroscopy to characterize their structural properties and intrinsic stabilities. Moreover, we used fluorescence spectroscopy to assay their aggregation propensities. Our results point to the importance of both dimerization strength and intrinsic monomer stability in stabilizing VL domains against aggregation. Notably, in all cases considered VL domains aggregate at least 10-fold faster than full-length LCs, establishing the important protective role of CL domains. A strong protective coupling is found between VL-VL and CL-CL dimer interfaces, with destabilization of one interface adversely affecting the stability of the other. Fibril formation is observed when either the VL or CL domain in the full-length protein is severely destabilized (i.e., where domain unfolding free energies are less than 2 kcal/mol). The important role of CL domains in preventing aggregation highlights the potential of the CL-CL interface as a target for the development of drugs to stabilize the dimeric LC structure and hence prevent LC amyloidosis.}, } @article {pmid30598438, year = {2019}, author = {Rainey, KH and Patterson, GH}, title = {Photoswitching FRET to monitor protein-protein interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {864-873}, doi = {10.1073/pnas.1805333116}, pmid = {30598438}, issn = {1091-6490}, abstract = {FRET is a powerful approach to study the interactions of fluorescent molecules, and numerous methods have been developed to measure FRET in cells. Here, we present a method based on a donor molecule's photoswitching properties, which are slower in the presence vs. the absence of an acceptor. The technique, photoswitching FRET (psFRET), is similar to an established but underutilized method called photobleaching FRET (pbFRET), with the major difference being that the molecules are switched "off" rather than photobleached. The psFRET technique has some of the FRET imaging advantages normally attributed to fluorescence lifetime imaging microscopy (FLIM), such as monitoring only donor fluorescence. However, it can be performed on a conventional widefield microscope, requires less illumination light to photoswitch off than photobleaching, and can be photoswitched "on" again to repeat the experiment. We present data testing the validity of the psFRET approach to quantify FRET in cells and demonstrate its use in imaging protein-protein interactions and fluorescent protein-based biosensors.}, } @article {pmid30598437, year = {2019}, author = {Keller, CB and Husson, JM and Mitchell, RN and Bottke, WF and Gernon, TM and Boehnke, P and Bell, EA and Swanson-Hysell, NL and Peters, SE}, title = {Neoproterozoic glacial origin of the Great Unconformity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {4}, pages = {1136-1145}, doi = {10.1073/pnas.1804350116}, pmid = {30598437}, issn = {1091-6490}, abstract = {The Great Unconformity, a profound gap in Earth's stratigraphic record often evident below the base of the Cambrian system, has remained among the most enigmatic field observations in Earth science for over a century. While long associated directly or indirectly with the occurrence of the earliest complex animal fossils, a conclusive explanation for the formation and global extent of the Great Unconformity has remained elusive. Here we show that the Great Unconformity is associated with a set of large global oxygen and hafnium isotope excursions in magmatic zircon that suggest a late Neoproterozoic crustal erosion and sediment subduction event of unprecedented scale. These excursions, the Great Unconformity, preservational irregularities in the terrestrial bolide impact record, and the first-order pattern of Phanerozoic sedimentation can together be explained by spatially heterogeneous Neoproterozoic glacial erosion totaling a global average of 3-5 vertical kilometers, along with the subsequent thermal and isostatic consequences of this erosion for global continental freeboard.}, } @article {pmid30598436, year = {2019}, author = {Weerasooriya, S and DiScipio, KA and Darwish, AS and Bai, P and Weller, SK}, title = {Herpes simplex virus 1 ICP8 mutant lacking annealing activity is deficient for viral DNA replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {1033-1042}, doi = {10.1073/pnas.1817642116}, pmid = {30598436}, issn = {1091-6490}, abstract = {Most DNA viruses that use recombination-dependent mechanisms to replicate their DNA encode a single-strand annealing protein (SSAP). The herpes simplex virus (HSV) single-strand DNA binding protein (SSB), ICP8, is the central player in all stages of DNA replication. ICP8 is a classical replicative SSB and interacts physically and/or functionally with the other viral replication proteins. Additionally, ICP8 can promote efficient annealing of complementary ssDNA and is thus considered to be a member of the SSAP family. The role of annealing during HSV infection has been difficult to assess in part, because it has not been possible to distinguish between the role of ICP8 as an SSAP from its role as a replicative SSB during viral replication. In this paper, we have characterized an ICP8 mutant, Q706A/F707A (QF), that lacks annealing activity but retains many other functions characteristic of replicative SSBs. Like WT ICP8, the QF mutant protein forms filaments in vitro, binds ssDNA cooperatively, and stimulates the activities of other replication proteins including the viral polymerase, helicase-primase complex, and the origin binding protein. Interestingly, the QF mutant does not complement an ICP8-null virus for viral growth, replication compartment formation, or DNA replication. Thus, we have been able to separate the activities of ICP8 as a replicative SSB from its annealing activity. Taken together, our data indicate that the annealing activity of ICP8 is essential for viral DNA replication in the context of infection and support the notion that HSV-1 uses recombination-dependent mechanisms during DNA replication.}, } @article {pmid30598435, year = {2019}, author = {Li, K and Jacob, DJ and Liao, H and Shen, L and Zhang, Q and Bates, KH}, title = {Anthropogenic drivers of 2013-2017 trends in summer surface ozone in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {422-427}, doi = {10.1073/pnas.1812168116}, pmid = {30598435}, issn = {1091-6490}, abstract = {Observations of surface ozone available from ∼1,000 sites across China for the past 5 years (2013-2017) show severe summertime pollution and regionally variable trends. We resolve the effect of meteorological variability on the ozone trends by using a multiple linear regression model. The residual of this regression shows increasing ozone trends of 1-3 ppbv a-1 in megacity clusters of eastern China that we attribute to changes in anthropogenic emissions. By contrast, ozone decreased in some areas of southern China. Anthropogenic NOx emissions in China are estimated to have decreased by 21% during 2013-2017, whereas volatile organic compounds (VOCs) emissions changed little. Decreasing NOx would increase ozone under the VOC-limited conditions thought to prevail in urban China while decreasing ozone under rural NOx-limited conditions. However, simulations with the Goddard Earth Observing System Chemical Transport Model (GEOS-Chem) indicate that a more important factor for ozone trends in the North China Plain is the ∼40% decrease of fine particulate matter (PM2.5) over the 2013-2017 period, slowing down the aerosol sink of hydroperoxy (HO2) radicals and thus stimulating ozone production.}, } @article {pmid30598434, year = {2019}, author = {Tang, F and Taylor, RJM and Einsle, JF and Borlina, CS and Fu, RR and Weiss, BP and Williams, HM and Williams, W and Nagy, L and Midgley, PA and Lima, EA and Bell, EA and Harrison, TM and Alexander, EW and Harrison, RJ}, title = {Secondary magnetite in ancient zircon precludes analysis of a Hadean geodynamo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {407-412}, doi = {10.1073/pnas.1811074116}, pmid = {30598434}, issn = {1091-6490}, abstract = {Zircon crystals from the Jack Hills, Western Australia, are one of the few surviving mineralogical records of Earth's first 500 million years and have been proposed to contain a paleomagnetic record of the Hadean geodynamo. A prerequisite for the preservation of Hadean magnetization is the presence of primary magnetic inclusions within pristine igneous zircon. To date no images of the magnetic recorders within ancient zircon have been presented. Here we use high-resolution transmission electron microscopy to demonstrate that all observed inclusions are secondary features formed via two distinct mechanisms. Magnetite is produced via a pipe-diffusion mechanism whereby iron diffuses into radiation-damaged zircon along the cores of dislocations and is precipitated inside nanopores and also during low-temperature recrystallization of radiation-damaged zircon in the presence of an aqueous fluid. Although these magnetites can be recognized as secondary using transmission electron microscopy, they otherwise occur in regions that are indistinguishable from pristine igneous zircon and carry remanent magnetization that postdates the crystallization age by at least several hundred million years. Without microscopic evidence ruling out secondary magnetite, the paleomagnetic case for a Hadean-Eoarchean geodynamo cannot yet been made.}, } @article {pmid30598433, year = {2019}, author = {Su, HJ and Barkman, TJ and Hao, W and Jones, SS and Naumann, J and Skippington, E and Wafula, EK and Hu, JM and Palmer, JD and dePamphilis, CW}, title = {Novel genetic code and record-setting AT-richness in the highly reduced plastid genome of the holoparasitic plant Balanophora.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {934-943}, doi = {10.1073/pnas.1816822116}, pmid = {30598433}, issn = {1091-6490}, abstract = {Plastid genomes (plastomes) vary enormously in size and gene content among the many lineages of nonphotosynthetic plants, but key lineages remain unexplored. We therefore investigated plastome sequence and expression in the holoparasitic and morphologically bizarre Balanophoraceae. The two Balanophora plastomes examined are remarkable, exhibiting features rarely if ever seen before in plastomes or in any other genomes. At 15.5 kb in size and with only 19 genes, they are among the most reduced plastomes known. They have no tRNA genes for protein synthesis, a trait found in only three other plastid lineages, and thus Balanophora plastids must import all tRNAs needed for translation. Balanophora plastomes are exceptionally compact, with numerous overlapping genes, highly reduced spacers, loss of all cis-spliced introns, and shrunken protein genes. With A+T contents of 87.8% and 88.4%, the Balanophora genomes are the most AT-rich genomes known save for a single mitochondrial genome that is merely bloated with AT-rich spacer DNA. Most plastid protein genes in Balanophora consist of ≥90% AT, with several between 95% and 98% AT, resulting in the most biased codon usage in any genome described to date. A potential consequence of its radical compositional evolution is the novel genetic code used by Balanophora plastids, in which TAG has been reassigned from stop to tryptophan. Despite its many exceptional properties, the Balanophora plastome must be functional because all examined genes are transcribed, its only intron is correctly trans-spliced, and its protein genes, although highly divergent, are evolving under various degrees of selective constraint.}, } @article {pmid30598432, year = {2019}, author = {Zhang, B and Zhuang, T and Lin, Q and Yang, B and Xu, X and Xin, G and Zhu, S and Wang, G and Yu, B and Zhang, T and Jiang, Q and Zhang, C}, title = {Patched1-ArhGAP36-PKA-Inversin axis determines the ciliary translocation of Smoothened for Sonic Hedgehog pathway activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {874-879}, doi = {10.1073/pnas.1804042116}, pmid = {30598432}, issn = {1091-6490}, abstract = {The Sonic Hedgehog (Shh) pathway conducts primarily in the primary cilium and plays important roles in cell proliferation, individual development, and tumorigenesis. Shh ligand binding with its ciliary membrane-localized transmembrane receptor Patched1 results in the removal of Patched1 from and the translocation of the transmembrane oncoprotein Smoothened into the cilium, leading to Shh signaling activation. However, how these processes are coupled remains unknown. Here, we show that the Patched1-ArhGAP36-PKA-Inversin axis determines the ciliary translocation of Smoothened. We find that Patched1 interacts with and stabilizes the PKA negative regulator ArhGAP36 to the centrosome. Activating the Shh pathway results in the removal of ArhGAP36 from the mother centriole and the centrosomal PKA accumulation. This PKA then phosphorylates Inversin and promotes its interaction with and the ciliary translocation of Smoothened. Knockdown of Inversin disrupts the ciliary translocation of Smoothened and Shh pathway activation. These findings reveal a regulatory molecular mechanism for the initial step of Shh pathway activation.}, } @article {pmid30598110, year = {2018}, author = {Zhao, L and Xie, J and Bai, L and Chen, W and Wang, M and Zhang, Z and Wang, Y and Zhao, Z and Li, J}, title = {Mining statistically-solid k-mers for accurate NGS error correction.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {912}, doi = {10.1186/s12864-018-5272-y}, pmid = {30598110}, issn = {1471-2164}, abstract = {BACKGROUND: NGS data contains many machine-induced errors. The most advanced methods for the error correction heavily depend on the selection of solid k-mers. A solid k-mer is a k-mer frequently occurring in NGS reads. The other k-mers are called weak k-mers. A solid k-mer does not likely contain errors, while a weak k-mer most likely contains errors. An intensively investigated problem is to find a good frequency cutoff f0 to balance the numbers of solid and weak k-mers. Once the cutoff is determined, a more challenging but less-studied problem is to: (i) remove a small subset of solid k-mers that are likely to contain errors, and (ii) add a small subset of weak k-mers, that are likely to contain no errors, into the remaining set of solid k-mers. Identification of these two subsets of k-mers can improve the correction performance.

RESULTS: We propose to use a Gamma distribution to model the frequencies of erroneous k-mers and a mixture of Gaussian distributions to model correct k-mers, and combine them to determine f0. To identify the two special subsets of k-mers, we use the z-score of k-mers which measures the number of standard deviations a k-mer's frequency is from the mean. Then these statistically-solid k-mers are used to construct a Bloom filter for error correction. Our method is markedly superior to the state-of-art methods, tested on both real and synthetic NGS data sets.

CONCLUSION: The z-score is adequate to distinguish solid k-mers from weak k-mers, particularly useful for pinpointing out solid k-mers having very low frequency. Applying z-score on k-mer can markedly improve the error correction accuracy.}, } @article {pmid30598109, year = {2018}, author = {Jiang, L and Xiao, Y and Ding, Y and Tang, J and Guo, F}, title = {FKL-Spa-LapRLS: an accurate method for identifying human microRNA-disease association.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {911}, doi = {10.1186/s12864-018-5273-x}, pmid = {30598109}, issn = {1471-2164}, abstract = {BACKGROUND: In the process of post-transcription, microRNAs (miRNAs) are closely related to various complex human diseases. Traditional verification methods for miRNA-disease associations take a lot of time and expense, so it is especially important to design computational methods for detecting potential associations. Considering the restrictions of previous computational methods for predicting potential miRNAs-disease associations, we develop the model of FKL-Spa-LapRLS (Fast Kernel Learning Sparse kernel Laplacian Regularized Least Squares) to break through the limitations.

RESULT: First, we extract three miRNA similarity kernels and three disease similarity kernels. Then, we combine these kernels into a single kernel through the Fast Kernel Learning (FKL) model, and use sparse kernel (Spa) to eliminate noise in the integrated similarity kernel. Finally, we find the associations via Laplacian Regularized Least Squares (LapRLS). Based on three evaluation methods, global and local leave-one-out cross validation (LOOCV), and 5-fold cross validation, the AUCs of our method achieve 0.9563, 0.8398 and 0.9535, thus it can be seen that our method is reliable. Then, we use case studies of eight neoplasms to further analyze the performance of our method. We find that most of the predicted miRNA-disease associations are confirmed by previous traditional experiments, and some important miRNAs should be paid more attention, which uncover more associations of various neoplasms than other miRNAs.

CONCLUSIONS: Our proposed model can reveal miRNA-disease associations and improve the accuracy of correlation prediction for various diseases. Our method can be also easily extended with more similarity kernels.}, } @article {pmid30598108, year = {2018}, author = {Xu, T and Su, N and Liu, L and Zhang, J and Wang, H and Zhang, W and Gui, J and Yu, K and Li, J and Le, TD}, title = {miRBaseConverter: an R/Bioconductor package for converting and retrieving miRNA name, accession, sequence and family information in different versions of miRBase.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {514}, doi = {10.1186/s12859-018-2531-5}, pmid = {30598108}, issn = {1471-2105}, abstract = {BACKGROUND: miRBase is the primary repository for published miRNA sequence and annotation data, and serves as the "go-to" place for miRNA research. However, the definition and annotation of miRNAs have been changed significantly across different versions of miRBase. The changes cause inconsistency in miRNA related data between different databases and articles published at different times. Several tools have been developed for different purposes of querying and converting the information of miRNAs between different miRBase versions, but none of them individually can provide the comprehensive information about miRNAs in miRBase and users will need to use a number of different tools in their analyses.

RESULTS: We introduce miRBaseConverter, an R package integrating the latest miRBase version 22 available in Bioconductor to provide a suite of functions for converting and retrieving miRNA name (ID), accession, sequence, species, version and family information in different versions of miRBase. The package is implemented in R and available under the GPL-2 license from the Bioconductor website (http://bioconductor.org/packages/miRBaseConverter/). A Shiny-based GUI suitable for non-R users is also available as a standalone application from the package and also as a web application at http://nugget.unisa.edu.au:3838/miRBaseConverter . miRBaseConverter has a built-in database for querying miRNA information in all species and for both pre-mature and mature miRNAs defined by miRBase. In addition, it is the first tool for batch querying the miRNA family information. The package aims to provide a comprehensive and easy-to-use tool for miRNA research community where researchers often utilize published miRNA data from different sources.

CONCLUSIONS: The Bioconductor package miRBaseConverter and the Shiny-based web application are presented to provide a suite of functions for converting and retrieving miRNA name, accession, sequence, species, version and family information in different versions of miRBase. The package will serve a wide range of applications in miRNA research and could provide a full view of the miRNAs of interest.}, } @article {pmid30598107, year = {2018}, author = {Wang, C and Zhang, S}, title = {Reveal cell type-specific regulatory elements and their characterized histone code classes via a hidden Markov model.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {903}, doi = {10.1186/s12864-018-5274-9}, pmid = {30598107}, issn = {1471-2164}, abstract = {BACKGROUND: With the maturity of next generation sequencing technology, a huge amount of epigenomic data have been generated by several large consortia in the last decade. These plenty resources leave us the opportunity about sufficiently utilizing those data to explore biological problems.

RESULTS: Here we developed an integrative and comparative method, CsreHMM, which is based on a hidden Markov model, to systematically reveal cell type-specific regulatory elements (CSREs) along the whole genome, and simultaneously recognize the histone codes (mark combinations) charactering them. This method also reveals the subclasses of CSREs and explicitly label those shared by a few cell types. We applied this method to a data set of 9 cell types and 9 chromatin marks to demonstrate its effectiveness and found that the revealed CSREs relates to different kinds of functional regulatory regions significantly. Their proximal genes have consistent expression and are likely to participate in cell type-specific biological functions.

CONCLUSIONS: These results suggest CsreHMM has the potential to help understand cell identity and the diverse mechanisms of gene regulation.}, } @article {pmid30598106, year = {2018}, author = {Pokoo, R and Ren, S and Wang, Q and Motes, CM and Hernandez, TD and Ahmadi, S and Monteros, MJ and Zheng, Y and Sunkar, R}, title = {Genotype- and tissue-specific miRNA profiles and their targets in three alfalfa (Medicago sativa L) genotypes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {913}, doi = {10.1186/s12864-018-5280-y}, pmid = {30598106}, issn = {1471-2164}, abstract = {BACKGROUND: Alfalfa (Medicago sativa L.) is a forage legume with significant agricultural value worldwide. MicroRNAs (miRNAs) are key components of post-transcriptional gene regulation and essentially regulate many aspects of plant growth and development. Although miRNAs were reported in alfalfa, their expression profiles in different tissues and the discovery of novel miRNAs as well as their targets have not been described in this plant species.

RESULTS: To identify tissue-specific miRNA profiles in whole plants, shoots and roots of three different alfalfa genotypes (Altet-4, NECS-141and NF08ALF06) were used. Small RNA libraries were generated and sequenced using a high-throughput sequencing platform. Analysis of these libraries enabled identification of100 miRNA families; 21 of them belong to the highly conserved families while the remaining 79 families are conserved at the minimum between M. sativa and the model legume and close relative, M. truncatula. The profiles of the six abundantly expressed miRNA families (miR156, miR159, miR166, miR319, miR396 and miR398) were relatively similar between the whole plants, roots and shoots of these three alfalfa genotypes. In contrast, robust differences between shoots and roots for miR160 and miR408 levels were evident, and their expression was more abundant in the shoots. Additionally, 17 novel miRNAs were identified and the relative abundance of some of these differed between tissue types. Further, the generation and analysis of degradome libraries from the three alfalfa genotypes enabled confirmation of 69 genes as targets for 31 miRNA families in alfalfa.

CONCLUSIONS: The miRNA profiles revealed both similarities and differences in the expression profiles between tissues within a genotype as well as between the genotypes. Among the highly conserved miRNA families, miR166 was the most abundantly expressed in almost all tissues from the three genotypes. The identification of conserved and novel miRNAs as well as their targets in different tissues of multiple genotypes increased our understanding of miRNA-mediated gene regulation in alfalfa and could provide valuable insights for practical research and plant improvement applications in alfalfa and related legume species.}, } @article {pmid30598105, year = {2018}, author = {Li, YF and Zheng, Y and Vemireddy, LR and Panda, SK and Jose, S and Ranjan, A and Panda, P and Govindan, G and Cui, J and Wei, K and Yaish, MW and Naidoo, GC and Sunkar, R}, title = {Comparative transcriptome and translatome analysis in contrasting rice genotypes reveals differential mRNA translation in salt-tolerant Pokkali under salt stress.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {935}, doi = {10.1186/s12864-018-5279-4}, pmid = {30598105}, issn = {1471-2164}, abstract = {BACKGROUND: Soil salinity is one of the primary causes of yield decline in rice. Pokkali (Pok) is a highly salt-tolerant landrace, whereas IR29 is a salt-sensitive but widely cultivated genotype. Comparative analysis of these genotypes may offer a better understanding of the salinity tolerance mechanisms in rice. Although most stress-responsive genes are regulated at the transcriptional level, in many cases, changes at the transcriptional level are not always accompanied with the changes in protein abundance, which suggests that the transcriptome needs to be studied in conjunction with the proteome to link the phenotype of stress tolerance or sensitivity. Published reports have largely underscored the importance of transcriptional regulation during salt stress in these genotypes, but the regulation at the translational level has been rarely studied. Using RNA-Seq, we simultaneously analyzed the transcriptome and translatome from control and salt-exposed Pok and IR29 seedlings to unravel molecular insights into gene regulatory mechanisms that differ between these genotypes.

RESULTS: Clear differences were evident at both transcriptional and translational levels between the two genotypes even under the control condition. In response to salt stress, 57 differentially expressed genes (DEGs) were commonly upregulated at both transcriptional and translational levels in both genotypes; the overall number of up/downregulated DEGs in IR29 was comparable at both transcriptional and translational levels, whereas in Pok, the number of upregulated DEGs was considerably higher at the translational level (544 DEGs) than at the transcriptional level (219 DEGs); in contrast, the number of downregulated DEGs (58) was significantly less at the translational level than at the transcriptional level (397 DEGs). These results imply that Pok stabilizes mRNAs and also efficiently loads mRNAs onto polysomes for translation during salt stress.

CONCLUSION: Under salt stress, Pok is more efficient in maintaining cell wall integrity, detoxifying reactive oxygen species (ROS), translocating molecules and maintaining photosynthesis. The present study confirmed the known salt stress-associated genes and also identified a number of putative new salt-responsive genes. Most importantly, the study revealed that the translational regulation under salinity plays an important role in salt-tolerant Pok, but such regulation was less evident in the salt-sensitive IR29.}, } @article {pmid30598104, year = {2018}, author = {Gao, X and Zhang, X and Meng, H and Li, J and Zhang, D and Liu, C}, title = {Comparative chloroplast genomes of Paris Sect. Marmorata: insights into repeat regions and evolutionary implications.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {878}, doi = {10.1186/s12864-018-5281-x}, pmid = {30598104}, issn = {1471-2164}, abstract = {BACKGROUND: Species of Paris Sect. Marmorata are valuable medicinal plants to synthesize steroidal saponins with effective pharmacological therapy. However, the wild resources of the species are threatened by plundering exploitation before the molecular genetics studies uncover the genomes and evolutionary significance. Thus, the availability of complete chloroplast genome sequences of Sect. Marmorata is necessary and crucial to the understanding the plastome evolution of this section and facilitating future population genetics studies. Here, we determined chloroplast genomes of Sect. Marmorata, and conducted the whole chloroplast genome comparison.

RESULTS: This study presented detailed sequences and structural variations of chloroplast genomes of Sect. Marmorata. Over 40 large repeats and approximately 130 simple sequence repeats as well as a group of genomic hotspots were detected. Inverted repeat contraction of this section was inferred via comparing the chloroplast genomes with the one of P. verticillata. Additionally, almost all the plastid protein coding genes were found to prefer ending with A/U. Mutation bias and selection pressure predominately shaped the codon bias of most genes. And most of the genes underwent purifying selection, whereas photosynthetic genes experienced a relatively relaxed purifying selection.

CONCLUSIONS: Repeat sequences and hotspot regions can be scanned to detect the intraspecific and interspecific variability, and selected to infer the phylogenetic relationships of Sect. Marmorata and other species in subgenus Daiswa. Mutation and natural selection were the main forces to drive the codon bias pattern of most plastid protein coding genes. Therefore, this study enhances the understanding about evolution of Sect. Marmorata from the chloroplast genome, and provide genomic insights into genetic analyses of Sect. Marmorata.}, } @article {pmid30598103, year = {2018}, author = {Zeng, C and Hamada, M}, title = {Identifying sequence features that drive ribosomal association for lncRNA.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {906}, doi = {10.1186/s12864-018-5275-8}, pmid = {30598103}, issn = {1471-2164}, abstract = {BACKGROUND: With the increasing number of annotated long noncoding RNAs (lncRNAs) from the genome, researchers are continually updating their understanding of lncRNAs. Recently, thousands of lncRNAs have been reported to be associated with ribosomes in mammals. However, their biological functions or mechanisms are still unclear.

RESULTS: In this study, we tried to investigate the sequence features involved in the ribosomal association of lncRNA. We have extracted ninety-nine sequence features corresponding to different biological mechanisms (i.e., RNA splicing, putative ORF, k-mer frequency, RNA modification, RNA secondary structure, and repeat element). An [Formula: see text]-regularized logistic regression model was applied to screen these features. Finally, we obtained fifteen and nine important features for the ribosomal association of human and mouse lncRNAs, respectively.

CONCLUSION: To our knowledge, this is the first study to characterize ribosome-associated lncRNAs and ribosome-free lncRNAs from the perspective of sequence features. These sequence features that were identified in this study may shed light on the biological mechanism of the ribosomal association and provide important clues for functional analysis of lncRNAs.}, } @article {pmid30598102, year = {2018}, author = {Zhou, X and Yin, R and Kwoh, CK and Zheng, J}, title = {A context-free encoding scheme of protein sequences for predicting antigenicity of diverse influenza A viruses.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {936}, doi = {10.1186/s12864-018-5282-9}, pmid = {30598102}, issn = {1471-2164}, abstract = {BACKGROUND: The evolution of influenza A viruses leads to the antigenic changes. Serological diagnosis of the antigenicity is usually labor-intensive, time-consuming and not suitable for early-stage detection. Computational prediction of the antigenic relationship between emerging and old strains of influenza viruses using viral sequences can facilitate large-scale antigenic characterization, especially for those viruses requiring high biosafety facilities, such as H5 and H7 influenza A viruses. However, most computational models require carefully designed subtype-specific features, thereby being restricted to only one subtype.

METHODS: In this paper, we propose a Context-FreeEncoding Scheme (CFreeEnS) for pairs of protein sequences, which encodes a protein sequence dataset into a numeric matrix and then feeds the matrix into a downstream machine learning model. CFreeEnS is not only free from subtype-specific selected features but also able to improve the accuracy of predicting the antigenicity of influenza. Since CFreeEnS is subtype-free, it is applicable to predicting the antigenicity of diverse influenza subtypes, hopefully saving the biologists from conducting serological assays for highly pathogenic strains.

RESULTS: The accuracy of prediction on each subtype tested (A/H1N1, A/H3N2, A/H5N1, A/H9N2) is over 85%, and can be as high as 91.5%. This outperforms existing methods that use carefully designed subtype-specific features. Furthermore, we tested the CFreeEnS on the combined dataset of the four subtypes. The accuracy reaches 84.6%, much higher than the best performance 75.1% reported by other subtype-free models, i.e. regional band-based model and residue-based model, for predicting the antigenicity of influenza. Also, we investigate the performance of CFreeEnS when the model is trained and tested on different subtypes (i.e. transfer learning). The prediction accuracy using CFreeEnS is 84.3% when the model is trained on the A/H1N1 dataset and tested on the A/H5N1, better than the 75.2% using a regional band-based model.

CONCLUSIONS: The CFreeEnS not only improves the prediction of antigenicity on datasets with only one subtype but also outperforms existing methods when tested on a combined dataset with four subtypes of influenza viruses.}, } @article {pmid30598101, year = {2018}, author = {Ma, S and Jiang, T and Jiang, R}, title = {Constructing tissue-specific transcriptional regulatory networks via a Markov random field.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {884}, doi = {10.1186/s12864-018-5277-6}, pmid = {30598101}, issn = {1471-2164}, abstract = {BACKGROUND: Recent advances in sequencing technologies have enabled parallel assays of chromatin accessibility and gene expression for major human cell lines. Such innovation provides a great opportunity to decode phenotypic consequences of genetic variation via the construction of predictive gene regulatory network models. However, there still lacks a computational method to systematically integrate chromatin accessibility information with gene expression data to recover complicated regulatory relationships between genes in a tissue-specific manner.

RESULTS: We propose a Markov random field (MRF) model for constructing tissue-specific transcriptional regulatory networks via integrative analysis of DNase-seq and RNA-seq data. Our method, named CSNets (cell-line specific regulatory networks), first infers regulatory networks for individual cell lines using chromatin accessibility information, and then fine-tunes these networks using the MRF based on pairwise similarity between cell lines derived from gene expression data. Using this method, we constructed regulatory networks specific to 110 human cell lines and 13 major tissues with the use of ENCODE data. We demonstrated the high quality of these networks via comprehensive statistical analysis based on ChIP-seq profiles, functional annotations, taxonomic analysis, and literature surveys. We further applied these networks to analyze GWAS data of Crohn's disease and prostate cancer. Results were either consistent with the literature or provided biological insights into regulatory mechanisms of these two complex diseases. The website of CSNets is freely available at http://bioinfo.au.tsinghua.edu.cn/jianglab/CSNETS/ .

CONCLUSIONS: CSNets demonstrated the power of joint analysis on epigenomic and transcriptomic data towards the accurate construction of gene regulatory network. Our work provides not only a useful resource of regulatory networks to the community, but also valuable experiences in methodology development for multi-omics data integration.}, } @article {pmid30598100, year = {2018}, author = {Zhang, L and Xue, G and Liu, J and Li, Q and Wang, Y}, title = {Revealing transcription factor and histone modification co-localization and dynamics across cell lines by integrating ChIP-seq and RNA-seq data.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {914}, doi = {10.1186/s12864-018-5278-5}, pmid = {30598100}, issn = {1471-2164}, abstract = {BACKGROUND: Interactions among transcription factors (TFs) and histone modifications (HMs) play an important role in the precise regulation of gene expression. The context specificity of those interactions and further its dynamics in normal and disease remains largely unknown. Recent development in genomics technology enables transcription profiling by RNA-seq and protein's binding profiling by ChIP-seq. Integrative analysis of the two types of data allows us to investigate TFs and HMs interactions both from the genome co-localization and downstream target gene expression.

RESULTS: We propose a integrative pipeline to explore the co-localization of 55 TFs and 11 HMs and its dynamics in human GM12878 and K562 by matched ChIP-seq and RNA-seq data from ENCODE. We classify TFs and HMs into three types based on their binding enrichment around transcription start site (TSS). Then a set of statistical indexes are proposed to characterize the TF-TF and TF-HM co-localizations. We found that Rad21, SMC3, and CTCF co-localized across five cell lines. High resolution Hi-C data in GM12878 shows that they associate most of the Hi-C peak loci with a specific CTCF-motif "anchor" and supports that CTCF, SMC3, and RAD2 co-localization serves important role in 3D chromatin structure. Meanwhile, 17 TF-TF pairs are highly dynamic between GM12878 and K562. We then build SVM models to correlate high and low expression level of target genes with TF binding and HM strength. We found that H3k9ac, H3k27ac, and three TFs (ELF1, TAF1, and POL2) are predictive with the accuracy about 85~92%.

CONCLUSION: We propose a pipeline to analyze the co-localization of TF and HM and their dynamics across cell lines from ChIP-seq, and investigate their regulatory potency by RNA-seq. The integrative analysis of two level data reveals new insight for the cooperation of TFs and HMs and is helpful in understanding cell line specificity of TF/HM interactions.}, } @article {pmid30598099, year = {2018}, author = {Abe, K and Hirayama, M and Ohno, K and Shimamura, T}, title = {A latent allocation model for the analysis of microbial composition and disease.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {519}, doi = {10.1186/s12859-018-2530-6}, pmid = {30598099}, issn = {1471-2105}, abstract = {BACKGROUND: Establishing the relationship between microbiota and specific diseases is important but requires appropriate statistical methodology. A specialized feature of microbiome count data is the presence of a large number of zeros, which makes it difficult to analyze in case-control studies. Most existing approaches either add a small number called a pseudo-count or use probability models such as the multinomial and Dirichlet-multinomial distributions to explain the excess zero counts, which may produce unnecessary biases and impose a correlation structure taht is unsuitable for microbiome data.

RESULTS: The purpose of this article is to develop a new probabilistic model, called BERnoulli and MUltinomial Distribution-based latent Allocation (BERMUDA), to address these problems. BERMUDA enables us to describe the differences in bacteria composition and a certain disease among samples. We also provide a simple and efficient learning procedure for the proposed model using an annealing EM algorithm.

CONCLUSION: We illustrate the performance of the proposed method both through both the simulation and real data analysis. BERMUDA is implemented with R and is available from GitHub (https://github.com/abikoushi/Bermuda).}, } @article {pmid30598098, year = {2018}, author = {Liu, L and Tang, L and Tang, M and Zhou, W}, title = {A partially function-to-topic model for protein function prediction.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {883}, doi = {10.1186/s12864-018-5276-7}, pmid = {30598098}, issn = {1471-2164}, abstract = {BACKGROUND: Proteins are a kind of macromolecules and the main component of a cell, and thus it is the most essential and versatile material of life. The research of protein functions is of great significance in decoding the secret of life. In recent years, researchers have introduced multi-label supervised topic model such as Labeled Latent Dirichlet Allocation (Labeled-LDA) into protein function prediction, which can obtain more accurate and explanatory prediction. However, the topic-label corresponding way of Labeled-LDA is associating each label (GO term) with a corresponding topic directly, which makes the latent topics to be completely degenerated, and ignores the differences between labels and latent topics.

RESULT: To achieve more accurate probabilistic modeling of function label, we propose a Partially Function-to-Topic Prediction (PFTP) model for introducing the local topics subset corresponding to each function label. Meanwhile, PFTP not only supports latent topics subset within a given function label but also a background topic corresponding to a 'fake' function label, which represents common semantic of protein function. Related definitions and the topic modeling process of PFTP are described in this paper. In a 5-fold cross validation experiment on yeast and human datasets, PFTP significantly outperforms five widely adopted methods for protein function prediction. Meanwhile, the impact of model parameters on prediction performance and the latent topics discovered by PFTP are also discussed in this paper.

CONCLUSION: All of the experimental results provide evidence that PFTP is effective and have potential value for predicting protein function. Based on its ability of discovering more-refined latent sub-structure of function label, we can anticipate that PFTP is a potential method to reveal a deeper biological explanation for protein functions.}, } @article {pmid30598097, year = {2018}, author = {Ata, SK and Ou-Yang, L and Fang, Y and Kwoh, CK and Wu, M and Li, XL}, title = {Integrating node embeddings and biological annotations for genes to predict disease-gene associations.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {138}, doi = {10.1186/s12918-018-0662-y}, pmid = {30598097}, issn = {1752-0509}, abstract = {BACKGROUND: Predicting disease causative genes (or simply, disease genes) has played critical roles in understanding the genetic basis of human diseases and further providing disease treatment guidelines. While various computational methods have been proposed for disease gene prediction, with the recent increasing availability of biological information for genes, it is highly motivated to leverage these valuable data sources and extract useful information for accurately predicting disease genes.

RESULTS: We present an integrative framework called N2VKO to predict disease genes. Firstly, we learn the node embeddings from protein-protein interaction (PPI) network for genes by adapting the well-known representation learning method node2vec. Secondly, we combine the learned node embeddings with various biological annotations as rich feature representation for genes, and subsequently build binary classification models for disease gene prediction. Finally, as the data for disease gene prediction is usually imbalanced (i.e. the number of the causative genes for a specific disease is much less than that of its non-causative genes), we further address this serious data imbalance issue by applying oversampling techniques for imbalance data correction to improve the prediction performance. Comprehensive experiments demonstrate that our proposed N2VKO significantly outperforms four state-of-the-art methods for disease gene prediction across seven diseases.

CONCLUSIONS: In this study, we show that node embeddings learned from PPI networks work well for disease gene prediction, while integrating node embeddings with other biological annotations further improves the performance of classification models. Moreover, oversampling techniques for imbalance correction further enhances the prediction performance. In addition, the literature search of predicted disease genes also shows the effectiveness of our proposed N2VKO framework for disease gene prediction.}, } @article {pmid30598096, year = {2018}, author = {Zhang, L and Yu, G and Guo, M and Wang, J}, title = {Predicting protein-protein interactions using high-quality non-interacting pairs.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {525}, doi = {10.1186/s12859-018-2525-3}, pmid = {30598096}, issn = {1471-2105}, abstract = {BACKGROUND: Identifying protein-protein interactions (PPIs) is of paramount importance for understanding cellular processes. Machine learning-based approaches have been developed to predict PPIs, but the effectiveness of these approaches is unsatisfactory. One major reason is that they randomly choose non-interacting protein pairs (negative samples) or heuristically select non-interacting pairs with low quality.

RESULTS: To boost the effectiveness of predicting PPIs, we propose two novel approaches (NIP-SS and NIP-RW) to generate high quality non-interacting pairs based on sequence similarity and random walk, respectively. Specifically, the known PPIs collected from public databases are used to generate the positive samples. NIP-SS then selects the top-m dissimilar protein pairs as negative examples and controls the degree distribution of selected proteins to construct the negative dataset. NIP-RW performs random walk on the PPI network to update the adjacency matrix of the network, and then selects protein pairs not connected in the updated network as negative samples. Next, we use auto covariance (AC) descriptor to encode the feature information of amino acid sequences. After that, we employ deep neural networks (DNNs) to predict PPIs based on extracted features, positive and negative examples. Extensive experiments show that NIP-SS and NIP-RW can generate negative samples with higher quality than existing strategies and thus enable more accurate prediction.

CONCLUSIONS: The experimental results prove that negative datasets constructed by NIP-SS and NIP-RW can reduce the bias and have good generalization ability. NIP-SS and NIP-RW can be used as a plugin to boost the effectiveness of PPIs prediction. Codes and datasets are available at http://mlda.swu.edu.cn/codes.php?name=NIP .}, } @article {pmid30598095, year = {2018}, author = {Jun, J and Gim, J and Kim, Y and Kim, H and Yu, SJ and Yeo, I and Park, J and Yoo, JJ and Cho, YY and Lee, DH and Cho, EJ and Lee, JH and Kim, YJ and Lee, S and Yoon, JH and Kim, Y and Park, T}, title = {Analysis of significant protein abundance from multiple reaction-monitoring data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {123}, doi = {10.1186/s12918-018-0656-9}, pmid = {30598095}, issn = {1752-0509}, abstract = {BACKGROUND: Discovering reliable protein biomarkers is one of the most important issues in biomedical research. The ELISA is a traditional technique for accurate quantitation of well-known proteins. Recently, the multiple reaction-monitoring (MRM) mass spectrometry has been proposed for quantifying newly discovered protein and has become a popular alternative to ELISA. For the MRM data analysis, linear mixed modeling (LMM) has been used to analyze MRM data. MSstats is one of the most widely used tools for MRM data analysis that is based on the LMMs. However, LMMs often provide various significance results, depending on model specification. Sometimes it would be difficult to specify a correct LMM method for the analysis of MRM data. Here, we propose a new logistic regression-based method for Significance Analysis of Multiple Reaction Monitoring (LR-SAM).

RESULTS: Through simulation studies, we demonstrate that LMM methods may not preserve type I error, thus yielding high false- positive errors, depending on how random effects are specified. Our simulation study also shows that the LR-SAM approach performs similarly well as LMM approaches, in most cases. However, LR-SAM performs better than the LMMs, particularly when the effects sizes of peptides from the same protein are heterogeneous. Our proposed method was applied to MRM data for identification of proteins associated with clinical responses of treatment of 115 hepatocellular carcinoma (HCC) patients with the tyrosine kinase inhibitor sorafenib. Of 124 candidate proteins, LMM approaches provided 6 results varying in significance, while LR-SAM, by contrast, yielded 18 significant results that were quite reproducibly consistent.

CONCLUSION: As exemplified by an application to HCC data set, LR-SAM more effectively identified proteins associated with clinical responses of treatment than LMM did.}, } @article {pmid30598094, year = {2018}, author = {Shi, JY and Zhang, AQ and Zhang, SW and Mao, KT and Yiu, SM}, title = {A unified solution for different scenarios of predicting drug-target interactions via triple matrix factorization.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {136}, doi = {10.1186/s12918-018-0663-x}, pmid = {30598094}, issn = {1752-0509}, abstract = {BACKGROUND: During the identification of potential candidates, computational prediction of drug-target interactions (DTIs) is important to subsequent expensive validation in wet-lab. DTI screening considers four scenarios, depending on whether the drug is an existing or a new drug and whether the target is an existing or a new target. However, existing approaches have the following limitations. First, only a few of them can address the most difficult scenario (i.e., predicting interactions between new drugs and new targets). More importantly, none of the existing approaches could provide the explicit information for understanding the mechanism of forming interactions, such as the drug-target feature pairs contributing to the interactions.

RESULTS: In this paper, we propose a Triple Matrix Factorization-based model (TMF) to tackle these problems. Compared with former state-of-the-art predictive methods, TMF demonstrates its significant superiority by assessing the predictions on four benchmark datasets over four kinds of screening scenarios. Also, it exhibits its outperformance by validating predicted novel interactions. More importantly, by using PubChem fingerprints of chemical structures as drug features and occurring frequencies of amino acid trimer as protein features, TMF shows its ability to find out the features determining interactions, including dominant feature pairs, frequently occurring substructures, and conserved triplet of amino acids.

CONCLUSIONS: Our TMF provides a unified framework of DTI prediction for all the screening scenarios. It also presents a new insight for the underlying mechanism of DTIs by indicating dominant features, which play important roles in the forming of DTI.}, } @article {pmid30598093, year = {2018}, author = {Wang, D and Li, J and Liu, R and Wang, Y}, title = {Optimizing gene set annotations combining GO structure and gene expression data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {133}, doi = {10.1186/s12918-018-0659-6}, pmid = {30598093}, issn = {1752-0509}, abstract = {BACKGROUND: With the rapid accumulation of genomic data, it has become a challenge issue to annotate and interpret these data. As a representative, Gene set enrichment analysis has been widely used to interpret large molecular datasets generated by biological experiments. The result of gene set enrichment analysis heavily relies on the quality and integrity of gene set annotations. Although several methods were developed to annotate gene sets, there is still a lack of high quality annotation methods. Here, we propose a novel method to improve the annotation accuracy through combining the GO structure and gene expression data.

RESULTS: We propose a novel approach for optimizing gene set annotations to get more accurate annotation results. The proposed method filters the inconsistent annotations using GO structure information and probabilistic gene set clusters calculated by a range of cluster sizes over multiple bootstrap resampled datasets. The proposed method is employed to analyze p53 cell lines, colon cancer and breast cancer gene expression data. The experimental results show that the proposed method can filter a number of annotations unrelated to experimental data and increase gene set enrichment power and decrease the inconsistent of annotations.

CONCLUSIONS: A novel gene set annotation optimization approach is proposed to improve the quality of gene annotations. Experimental results indicate that the proposed method effectively improves gene set annotation quality based on the GO structure and gene expression data.}, } @article {pmid30598091, year = {2018}, author = {Liu, Q and Chen, P and Wang, B and Zhang, J and Li, J}, title = {Hot spot prediction in protein-protein interactions by an ensemble system.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {132}, doi = {10.1186/s12918-018-0665-8}, pmid = {30598091}, issn = {1752-0509}, abstract = {BACKGROUND: Hot spot residues are functional sites in protein interaction interfaces. The identification of hot spot residues is time-consuming and laborious using experimental methods. In order to address the issue, many computational methods have been developed to predict hot spot residues. Moreover, most prediction methods are based on structural features, sequence characteristics, and/or other protein features.

RESULTS: This paper proposed an ensemble learning method to predict hot spot residues that only uses sequence features and the relative accessible surface area of amino acid sequences. In this work, a novel feature selection technique was developed, an auto-correlation function combined with a sliding window technique was applied to obtain the characteristics of amino acid residues in protein sequence, and an ensemble classifier with SVM and KNN base classifiers was built to achieve the best classification performance.

CONCLUSION: The experimental results showed that our model yields the highest F1 score of 0.92 and an MCC value of 0.87 on ASEdb dataset. Compared with other machine learning methods, our model achieves a big improvement in hot spot prediction.

AVAILABILITY: http://deeplearner.ahu.edu.cn/web/HotspotEL.htm .}, } @article {pmid30598090, year = {2018}, author = {Sun, Y and Zhu, Z and You, ZH and Zeng, Z and Huang, ZA and Huang, YA}, title = {FMSM: a novel computational model for predicting potential miRNA biomarkers for various human diseases.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {121}, doi = {10.1186/s12918-018-0664-9}, pmid = {30598090}, issn = {1752-0509}, abstract = {BACKGROUND: MicroRNA (miRNA) plays a key role in regulation mechanism of human biological processes, including the development of disease and disorder. It is necessary to identify potential miRNA biomarkers for various human diseases. Computational prediction model is expected to accelerate the process of identification.

RESULTS: Considering the limitations of previously proposed models, we present a novel computational model called FMSM. It infers latent miRNA biomarkers involved in the mechanism of various diseases based on the known miRNA-disease association network, miRNA expression similarity, disease semantic similarity and Gaussian interaction profile kernel similarity. FMSM achieves reliable prediction performance in 5-fold and leave-one-out cross validations with area under ROC curve (AUC) values of 0.9629+/- 0.0127 and 0.9433, respectively, which outperforms the state-of-the-art competitors and classical algorithms. In addition, 19 of top 25 predicted miRNAs have been validated to have associations with Colonic Neoplasms in case study.

CONCLUSIONS: A factored miRNA similarity based model and miRNA expression similarity substantially contribute to the well-performing prediction. The list of the predicted most latent miRNA biomarkers of various human diseases is publicized. It is anticipated that FMSM could serve as a useful tool guiding the future experimental validation for those promising miRNA biomarker candidates.}, } @article {pmid30598088, year = {2018}, author = {Wen, Y and Han, G and Anh, VV}, title = {Laplacian normalization and bi-random walks on heterogeneous networks for predicting lncRNA-disease associations.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {122}, doi = {10.1186/s12918-018-0660-0}, pmid = {30598088}, issn = {1752-0509}, abstract = {BACKGROUND: Evidences have increasingly indicated that lncRNAs (long non-coding RNAs) are deeply involved in important biological regulation processes leading to various human complex diseases. Experimental investigations of these disease associated lncRNAs are slow with high costs. Computational methods to infer potential associations between lncRNAs and diseases have become an effective prior-pinpointing approach to the experimental verification.

RESULTS: In this study, we develop a novel method for the prediction of lncRNA-disease associations using bi-random walks on a network merging the similarities of lncRNAs and diseases. Particularly, this method applies a Laplacian technique to normalize the lncRNA similarity matrix and the disease similarity matrix before the construction of the lncRNA similarity network and disease similarity network. The two networks are then connected via existing lncRNA-disease associations. After that, bi-random walks are applied on the heterogeneous network to predict the potential associations between the lncRNAs and the diseases. Experimental results demonstrate that the performance of our method is highly comparable to or better than the state-of-the-art methods for predicting lncRNA-disease associations. Our analyses on three cancer data sets (breast cancer, lung cancer, and liver cancer) also indicate the usefulness of our method in practical applications.

CONCLUSIONS: Our proposed method, including the construction of the lncRNA similarity network and disease similarity network and the bi-random walks algorithm on the heterogeneous network, could be used for prediction of potential associations between the lncRNAs and the diseases.}, } @article {pmid30598087, year = {2018}, author = {Chen, KT and Shen, HT and Lu, CL}, title = {Multi-CSAR: a multiple reference-based contig scaffolder using algebraic rearrangements.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {139}, doi = {10.1186/s12918-018-0654-y}, pmid = {30598087}, issn = {1752-0509}, abstract = {BACKGROUND: One of the important steps in the process of assembling a genome sequence from short reads is scaffolding, in which the contigs in a draft genome are ordered and oriented into scaffolds. Currently, several scaffolding tools based on a single reference genome have been developed. However, a single reference genome may not be sufficient alone for a scaffolder to generate correct scaffolds of a target draft genome, especially when the evolutionary relationship between the target and reference genomes is distant or some rearrangements occur between them. This motivates the need to develop scaffolding tools that can order and orient the contigs of the target genome using multiple reference genomes.

RESULTS: In this work, we utilize a heuristic method to develop a new scaffolder called Multi-CSAR that is able to accurately scaffold a target draft genome based on multiple reference genomes, each of which does not need to be complete. Our experimental results on real datasets show that Multi-CSAR outperforms other two multiple reference-based scaffolding tools, Ragout and MeDuSa, in terms of many average metrics, such as sensitivity, precision, F-score, genome coverage, NGA50, scaffold number and running time.

CONCLUSIONS: Multi-CSAR is a multiple reference-based scaffolder that can efficiently produce more accurate scaffolds of a target draft genome by referring to multiple complete and/or incomplete genomes of related organisms. Its stand-alone program is available for download at https://github.com/ablab-nthu/Multi-CSAR.}, } @article {pmid30598086, year = {2018}, author = {Cai, M and Li, L}, title = {rPCMP: robust p-value combination by multiple partitions with applications to ATAC-seq data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {141}, doi = {10.1186/s12918-018-0661-z}, pmid = {30598086}, issn = {1752-0509}, abstract = {BACKGROUND: Evaluating the significance for a group of genes or proteins in a pathway or biological process for a disease could help researchers understand the mechanism of the disease. For example, identifying related pathways or gene functions for chromatin states of tumor-specific T cells will help determine whether T cells could reprogram or not, and further help design the cancer treatment strategy. Some existing p-value combination methods can be used in this scenario. However, these methods suffer from different disadvantages, and thus it is still challenging to design more powerful and robust statistical method.

RESULTS: The existing method of Group combined p-value (GCP) first partitions p-values to several groups using a set of several truncation points, but the method is often sensitive to these truncation points. Another method of adaptive rank truncated product method(ARTP) makes use of multiple truncation integers to adaptively combine the smallest p-values, but the method loses statistical power since it ignores the larger p-values. To tackle these problems, we propose a robust p-value combination method (rPCMP) by considering multiple partitions of p-values with different sets of truncation points. The proposed rPCMP statistic have a three-layer hierarchical structure. The inner-layer considers a statistic which combines p-values in a specified interval defined by two thresholds points, the intermediate-layer uses a GCP statistic which optimizes the statistic from the inner layer for a partition set of threshold points, and the outer-layer integrates the GCP statistic from multiple partitions of p-values. The empirical distribution of statistic under null distribution could be estimated by permutation procedure.

CONCLUSIONS: Our proposed rPCMP method has been shown to be more robust and have higher statistical power. Simulation study shows that our method can effectively control the type I error rates and have higher statistical power than the existing methods. We finally apply our rPCMP method to an ATAC-seq dataset for discovering the related gene functions with chromatin states in mouse tumors T cell.}, } @article {pmid30598085, year = {2018}, author = {Zhang, K and Geng, W and Zhang, S}, title = {Network-based logistic regression integration method for biomarker identification.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {135}, doi = {10.1186/s12918-018-0657-8}, pmid = {30598085}, issn = {1752-0509}, abstract = {BACKGROUND: Many mathematical and statistical models and algorithms have been proposed to do biomarker identification in recent years. However, the biomarkers inferred from different datasets suffer a lack of reproducibilities due to the heterogeneity of the data generated from different platforms or laboratories. This motivates us to develop robust biomarker identification methods by integrating multiple datasets.

METHODS: In this paper, we developed an integrative method for classification based on logistic regression. Different constant terms are set in the logistic regression model to measure the heterogeneity of the samples. By minimizing the differences of the constant terms within the same dataset, both the homogeneity within the same dataset and the heterogeneity in multiple datasets can be kept. The model is formulated as an optimization problem with a network penalty measuring the differences of the constant terms. The L1 penalty, elastic penalty and network related penalties are added to the objective function for the biomarker discovery purpose. Algorithms based on proximal Newton method are proposed to solve the optimization problem.

RESULTS: We first applied the proposed method to the simulated datasets. Both the AUC of the prediction and the biomarker identification accuracy are improved. We then applied the method to two breast cancer gene expression datasets. By integrating both datasets, the prediction AUC is improved over directly merging the datasets and MetaLasso. And it's comparable to the best AUC when doing biomarker identification in an individual dataset. The identified biomarkers using network related penalty for variables were further analyzed. Meaningful subnetworks enriched by breast cancer were identified.

CONCLUSION: A network-based integrative logistic regression model is proposed in the paper. It improves both the prediction and biomarker identification accuracy.}, } @article {pmid30598084, year = {2018}, author = {Tian, Z and Teng, Z and Cheng, S and Guo, M}, title = {Computational drug repositioning using meta-path-based semantic network analysis.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {134}, doi = {10.1186/s12918-018-0658-7}, pmid = {30598084}, issn = {1752-0509}, abstract = {BACKGROUND: Drug repositioning is a promising and efficient way to discover new indications for existing drugs, which holds the great potential for precision medicine in the post-genomic era. Many network-based approaches have been proposed for drug repositioning based on similarity networks, which integrate multiple sources of drugs and diseases. However, these methods may simply view nodes as the same-typed and neglect the semantic meanings of different meta-paths in the heterogeneous network. Therefore, it is urgent to develop a rational method to infer new indications for approved drugs.

RESULTS: In this study, we proposed a novel methodology named HeteSim_DrugDisease (HSDD) for the prediction of drug repositioning. Firstly, we build the drug-drug similarity network and disease-disease similarity network by integrating the information of drugs and diseases. Secondly, a drug-disease heterogeneous network is constructed, which combines the drug similarity network, disease similarity network as well as the known drug-disease association network. Finally, HSDD predicts novel drug-disease associations based on the HeteSim scores of different meta-paths. The experimental results show that HSDD performs significantly better than the existing state-of-the-art approaches. HSDD achieves an AUC score of 0.8994 in the leave-one-out cross validation experiment. Moreover, case studies for selected drugs further illustrate the practical usefulness of HSDD.

CONCLUSIONS: HSDD can be an effective and feasible way to infer the associations between drugs and diseases using on meta-path-based semantic network analysis.}, } @article {pmid30598083, year = {2018}, author = {Kabir, MH and Patrick, R and Ho, JWK and O'Connor, MD}, title = {Identification of active signaling pathways by integrating gene expression and protein interaction data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 9}, pages = {120}, doi = {10.1186/s12918-018-0655-x}, pmid = {30598083}, issn = {1752-0509}, abstract = {BACKGROUND: Signaling pathways are the key biological mechanisms that transduce extracellular signals to affect transcription factor mediated gene regulation within cells. A number of computational methods have been developed to identify the topological structure of a specific signaling pathway using protein-protein interaction data, but they are not designed for identifying active signaling pathways in an unbiased manner. On the other hand, there are statistical methods based on gene sets or pathway data that can prioritize likely active signaling pathways, but they do not make full use of active pathway structure that link receptor, kinases and downstream transcription factors.

RESULTS: Here, we present a method to simultaneously predict the set of active signaling pathways, together with their pathway structure, by integrating protein-protein interaction network and gene expression data. We evaluated the capacity for our method to predict active signaling pathways for dental epithelial cells, ocular lens epithelial cells, human pluripotent stem cell-derived lens epithelial cells, and lens fiber cells. This analysis showed our approach could identify all the known active pathways that are associated with tooth formation and lens development.

CONCLUSIONS: The results suggest that SPAGI can be a useful approach to identify the potential active signaling pathways given a gene expression profile. Our method is implemented as an open source R package, available via https://github.com/VCCRI/SPAGI/ .}, } @article {pmid30598081, year = {2018}, author = {Chen, HM and Chen, CC and Chen, CC and Wang, SC and Wang, CL and Huang, CH and Liou, JS and Liu, TW and Peng, HL and Lin, FM and Liu, CY and Weng, SL and Cheng, CJ and Hung, YF and Liao, CC and Huang, HD}, title = {Gut microbiome changes in overweight male adults following bowel preparation.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {904}, doi = {10.1186/s12864-018-5285-6}, pmid = {30598081}, issn = {1471-2164}, abstract = {BACKGROUND: Human gut microbiome has an essential role in human health and disease. Although the major dominant microbiota within individuals have been reported, the change of gut microbiome caused by external factors, such as antibiotic use and bowel cleansing, remains unclear. We conducted this study to investigate the change of gut microbiome in overweight male adults after bowel preparation, where none of the participants had been diagnosed with any systemic diseases.

METHODS: A total of 20 overweight, male Taiwanese adults were recruited, and all participants were omnivorous. The participants provided fecal samples and blood samples at three time points: prior to bowel preparation, 7 days after colonoscopy, and 28 days after colonoscopy. The microbiota composition in fecal samples was analyzed using 16S ribosome RNA gene amplicon sequencing.

RESULTS: Our results demonstrated that the relative abundance of the most dominant bacteria hardly changed from prior to bowel preparation to 28 days after colonoscopy. Using the ratio of Prevotella to the sum of Prevotella and Bacteroides in the fecal samples at baseline, the participants were separated into two groups. The fecal samples of the Type 1 group was Bacteroides-dominant, and that of the Type 2 group was Prevotella-dominant with a noticeable presence Bacteroides. Bulleidia appears more in the Type 1 fecal samples, while Akkermensia appears more in the Type 2 fecal samples. Of each type, the gut microbial diversity differed slightly among the three collection times. Additionally, the Type 2 fecal microbiota was temporarily susceptible to bowel cleansing. Predictive functional analysis of microbial community reveals that their activities for the mineral absorption metabolism and arachidonic acid metabolism differed significantly between the two types. Depending on their fecal type, the variance of triglycerides and C-reactive protein also differed between the two types of participants.

CONCLUSIONS: Depending upon the fecal type, the microbial diversity and the predictive functional modules of microbial community differed significantly after bowel preparation. In addition, blood biochemical markers presented somewhat associated with fecal type. Therefore, our results might provide some insights as to how knowledge of the microbial community could be used to promote health through personalized clinical treatment.}, } @article {pmid30598080, year = {2018}, author = {Chen, HM and Chang, TH and Lin, FM and Liang, C and Chiu, CM and Yang, TL and Yang, T and Huang, CY and Cheng, YN and Chang, YA and Chang, PY and Weng, SL}, title = {Vaginal microbiome variances in sample groups categorized by clinical criteria of bacterial vaginosis.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {876}, doi = {10.1186/s12864-018-5284-7}, pmid = {30598080}, issn = {1471-2164}, abstract = {BACKGROUND: One of the most common and recurrent vaginal infections is bacterial vaginosis (BV). The diagnosis is based on changes to the "normal" vaginal microbiome; however, the normal microbiome appears to differ according to reproductive status and ethnicity, and even among individuals within these groups. The Amsel criteria and Nugent score test are widely used for diagnosing BV; however, these tests are based on different criteria, and so may indicate distinct changes in the vaginal microbial community. Nevertheless, few studies have compared the results of these test against metagenomics analysis.

METHODS: Vaginal flora samples from 77 participants were classified according to the Amsel criteria and Nugent score test. The microbiota composition was analyzed using 16S ribosome RNA gene amplicon sequencing. Bioinformatics analysis and multivariate statistical analysis were used to evaluate the microbial diversity and function.

RESULTS: Only 3 % of the participants diagnosed BV negative using the Amsel criteria (A-) were BV-positive according to the Nugent score test (N+), while over half of the BV-positive patients using the Amsel criteria (A+) were BV-negative according to the Nugent score test (N-). Thirteen genera showed significant differences in distribution among BV status defined by BV tests (e.g., A - N-, A + N- and A + N+). Variations in the four most abundant taxa, Lactobacillus, Gardnerella, Prevotella, and Escherichia, were responsible for most of this dissimilarity. Furthermore, vaginal microbial diversity differed significantly among the three groups classified by the Nugent score test (N-, N+, and intermediate flora), but not between the Amsel criteria groups. Numerous predictive microbial functions, such as bacterial chemotaxis and bacterial invasion of epithelial cells, differed significantly among multiple BV test, but not between the A- and A+ groups.

CONCLUSIONS: Metagenomics analysis can greatly expand our current understanding of vaginal microbial diversity in health and disease. Metagenomics profiling may also provide more reliable diagnostic criteria for BV testing.}, } @article {pmid30598079, year = {2018}, author = {Lyu, C and Wang, L and Zhang, J}, title = {Deep learning for DNase I hypersensitive sites identification.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 10}, pages = {905}, doi = {10.1186/s12864-018-5283-8}, pmid = {30598079}, issn = {1471-2164}, abstract = {BACKGROUND: The DNase I hypersensitive sites (DHSs) are associated with the cis-regulatory DNA elements. An efficient method of identifying DHSs can enhance the understanding on the accessibility of chromatin. Despite a multitude of resources available on line including experimental datasets and computational tools, the complex language of DHSs remains incompletely understood.

METHODS: Here, we address this challenge using an approach based on a state-of-the-art machine learning method. We present a novel convolutional neural network (CNN) which combined Inception like networks with a gating mechanism for the response of multiple patterns and longterm association in DNA sequences to predict multi-scale DHSs in Arabidopsis, rice and Homo sapiens.

RESULTS: Our method obtains 0.961 area under curve (AUC) on Arabidopsis, 0.969 AUC on rice and 0.918 AUC on Homo sapiens.

CONCLUSIONS: Our method provides an efficient and accurate way to identify multi-scale DHSs sequences by deep learning.}, } @article {pmid30598077, year = {2018}, author = {Yang, X and Song, Z and Wu, C and Wang, W and Li, G and Zhang, W and Wu, L and Lu, K}, title = {Constructing a database for the relations between CNV and human genetic diseases via systematic text mining.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {528}, doi = {10.1186/s12859-018-2526-2}, pmid = {30598077}, issn = {1471-2105}, abstract = {BACKGROUND: The detection and interpretation of CNVs are of clinical importance in genetic testing. Several databases and web services are already being used by clinical geneticists to interpret the medical relevance of identified CNVs in patients. However, geneticists or physicians would like to obtain the original literature context for more detailed information, especially for rare CNVs that were not included in databases.

RESULTS: The resulting CNVdigest database includes 440,485 sentences for CNV-disease relationship. A total number of 1582 CNVs and 2425 diseases are involved. Sentences describing CNV-disease correlations are indexed in CNVdigest, with CNV mentions and disease mentions annotated.

CONCLUSIONS: In this paper, we use a systematic text mining method to construct a database for the relationship between CNVs and diseases. Based on that, we also developed a concise front-end to facilitate the analysis of CNV/disease association, providing a user-friendly web interface for convenient queries. The resulting system is publically available at http://cnv.gtxlab.com /.}, } @article {pmid30598076, year = {2018}, author = {Yan, C and Wang, J and Wu, FX}, title = {DWNN-RLS: regularized least squares method for predicting circRNA-disease associations.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {520}, doi = {10.1186/s12859-018-2522-6}, pmid = {30598076}, issn = {1471-2105}, abstract = {BACKGROUND: Many evidences have demonstrated that circRNAs (circular RNA) play important roles in controlling gene expression of human, mouse and nematode. More importantly, circRNAs are also involved in many diseases through fine tuning of post-transcriptional gene expression by sequestering the miRNAs which associate with diseases. Therefore, identifying the circRNA-disease associations is very appealing to comprehensively understand the mechanism, treatment and diagnose of diseases, yet challenging. As the complex mechanism between circRNAs and diseases, wet-lab experiments are expensive and time-consuming to discover novel circRNA-disease associations. Therefore, it is of dire need to employ the computational methods to discover novel circRNA-disease associations.

RESULT: In this study, we develop a method (DWNN-RLS) to predict circRNA-disease associations based on Regularized Least Squares of Kronecker product kernel. The similarity of circRNAs is computed from the Gaussian Interaction Profile(GIP) based on known circRNA-disease associations. In addition, the similarity of diseases is integrated by the mean of GIP similarity and sematic similarity which is computed by the direct acyclic graph (DAG) representation of diseases. The kernels of circRNA-disease pairs are constructed from the Kronecker product of the kernels of circRNAs and diseases. DWNN (decreasing weight k-nearest neighbor) method is adopted to calculate the initial relational score for new circRNAs and diseases. The Kronecker product kernel based regularised least squares approach is used to predict new circRNA-disease associations. We adopt 5-fold cross validation (5CV), 10-fold cross validation (10CV) and leave one out cross validation (LOOCV) to assess the prediction performance of our method, and compare it with other six competing methods (RLS-avg, RLS-Kron, NetLapRLS, KATZ, NBI, WP).

CONLUSION: The experiment results show that DWNN-RLS reaches the AUC values of 0.8854, 0.9205 and 0.9701 in 5CV, 10CV and LOOCV, respectively, which illustrates that DWNN-RLS is superior to the competing methods RLS-avg, RLS-Kron, NetLapRLS, KATZ, NBI, WP. In addition, case studies also show that DWNN-RLS is an effective method to predict new circRNA-disease associations.}, } @article {pmid30598075, year = {2018}, author = {Hirohara, M and Saito, Y and Koda, Y and Sato, K and Sakakibara, Y}, title = {Convolutional neural network based on SMILES representation of compounds for detecting chemical motif.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {526}, doi = {10.1186/s12859-018-2523-5}, pmid = {30598075}, issn = {1471-2105}, abstract = {BACKGROUND: Previous studies have suggested deep learning to be a highly effective approach for screening lead compounds for new drugs. Several deep learning models have been developed by addressing the use of various kinds of fingerprints and graph convolution architectures. However, these methods are either advantageous or disadvantageous depending on whether they (1) can distinguish structural differences including chirality of compounds, and (2) can automatically discover effective features.

RESULTS: We developed another deep learning model for compound classification. In this method, we constructed a distributed representation of compounds based on the SMILES notation, which linearly represents a compound structure, and applied the SMILES-based representation to a convolutional neural network (CNN). The use of SMILES allows us to process all types of compounds while incorporating a broad range of structure information, and representation learning by CNN automatically acquires a low-dimensional representation of input features. In a benchmark experiment using the TOX 21 dataset, our method outperformed conventional fingerprint methods, and performed comparably against the winning model of the TOX 21 Challenge. Multivariate analysis confirmed that the chemical space consisting of the features learned by SMILES-based representation learning adequately expressed a richer feature space that enabled the accurate discrimination of compounds. Using motif detection with the learned filters, not only important known structures (motifs) such as protein-binding sites but also structures of unknown functional groups were detected.

CONCLUSIONS: The source code of our SMILES-based convolutional neural network software in the deep learning framework Chainer is available at http://www.dna.bio.keio.ac.jp/smiles/ , and the dataset used for performance evaluation in this work is available at the same URL.}, } @article {pmid30598074, year = {2018}, author = {Pei, S and Guan, J and Zhou, S}, title = {Classifying early and late mild cognitive impairment stages of Alzheimer's disease by fusing default mode networks extracted with multiple seeds.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {523}, doi = {10.1186/s12859-018-2528-0}, pmid = {30598074}, issn = {1471-2105}, abstract = {BACKGROUND: The default mode network (DMN) in resting state has been increasingly used in disease diagnosis since it was found in 2001. Prior work has mainly focused on extracting a single DMN with various techniques. However, by using seeding-based analysis with more than one desirable seed, we can obtain multiple DMNs, which are likely to have complementary information, and thus are more promising for disease diagnosis. In the study, we used 18 early mild cognitive impairment (EMCI) participants and 18 late mild cognitive impairment (LMCI) participants of Alzheimer's disease (AD). First, we used seeding-based analysis with four seeds to extract four DMNs for each subject. Then, we conducted fusion analysis for all different combinations of the four DMNs. Finally, we carried out nonlinear support vector machine classification based on the mixing coefficients from the fusion analysis.

RESULTS: We found that (1) the four DMNs corresponding to the four different seeds indeed capture different functional regions of each subject; (2) Maps of the four DMNs in the most different joint source from fusion analysis are centered at the regions of the corresponding seeds; (3) Classification results reveal the effectiveness of using multiple seeds to extract DMNs. When using a single seed, the regions of posterior cingulate cortex (PCC) extractions of EMCI and LMCI show the largest difference. For multiple-seed cases, the regions of PCC extraction and right lateral parietal cortex (RLP) extraction provide complementary information for each other in fusion, which improves the classification accuracy. Furthermore, the regions of left lateral parietal cortex (LLP) extraction and RLP extraction also have complementary effect in fusion. In summary, AD diagnosis can be improved by exploiting complementary information of DMNs extracted with multiple seeds.

CONCLUSIONS: In this study, we applied fusion analysis to the DMNs extracted by using different seeds for exploiting the complementary information hidden among the separately extracted DMNs, and the results supported our expectation that using the complementary information can improve classification accuracy.}, } @article {pmid30598073, year = {2018}, author = {Deng, L and Pan, J and Xu, X and Yang, W and Liu, C and Liu, H}, title = {PDRLGB: precise DNA-binding residue prediction using a light gradient boosting machine.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {522}, doi = {10.1186/s12859-018-2527-1}, pmid = {30598073}, issn = {1471-2105}, abstract = {BACKGROUND: Identifying specific residues for protein-DNA interactions are of considerable importance to better recognize the binding mechanism of protein-DNA complexes. Despite the fact that many computational DNA-binding residue prediction approaches have been developed, there is still significant room for improvement concerning overall performance and availability.

RESULTS: Here, we present an efficient approach termed PDRLGB that uses a light gradient boosting machine (LightGBM) to predict binding residues in protein-DNA complexes. Initially, we extract a wide variety of 913 sequence and structure features with a sliding window of 11. Then, we apply the random forest algorithm to sort the features in descending order of importance and obtain the optimal subset of features using incremental feature selection. Based on the selected feature set, we use a light gradient boosting machine to build the prediction model for DNA-binding residues. Our PDRLGB method shows better overall predictive accuracy and relatively less training time than other widely used machine learning (ML) methods such as random forest (RF), Adaboost and support vector machine (SVM). We further compare PDRLGB with various existing approaches on the independent test datasets and show improvement in results over the existing state-of-the-art approaches.

CONCLUSIONS: PDRLGB is an efficient approach to predict specific residues for protein-DNA interactions.}, } @article {pmid30598072, year = {2018}, author = {Tajimi, T and Wakui, N and Yanagisawa, K and Yoshikawa, Y and Ohue, M and Akiyama, Y}, title = {Computational prediction of plasma protein binding of cyclic peptides from small molecule experimental data using sparse modeling techniques.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {527}, doi = {10.1186/s12859-018-2529-z}, pmid = {30598072}, issn = {1471-2105}, abstract = {BACKGROUND: Cyclic peptide-based drug discovery is attracting increasing interest owing to its potential to avoid target protein depletion. In drug discovery, it is important to maintain the biostability of a drug within the proper range. Plasma protein binding (PPB) is the most important index of biostability, and developing a computational method to predict PPB of drug candidate compounds contributes to the acceleration of drug discovery research. PPB prediction of small molecule drug compounds using machine learning has been conducted thus far; however, no study has investigated cyclic peptides because experimental information of cyclic peptides is scarce.

RESULTS: First, we adopted sparse modeling and small molecule information to construct a PPB prediction model for cyclic peptides. As cyclic peptide data are limited, applying multidimensional nonlinear models involves concerns regarding overfitting. However, models constructed by sparse modeling can avoid overfitting, offering high generalization performance and interpretability. More than 1000 PPB data of small molecules are available, and we used them to construct a prediction models with two enumeration methods: enumerating lasso solutions (ELS) and forward beam search (FBS). The accuracies of the prediction models constructed by ELS and FBS were equal to or better than those of conventional non-linear models (MAE = 0.167-0.174) on cross-validation of a small molecule compound dataset. Moreover, we showed that the prediction accuracies for cyclic peptides were close to those for small molecule compounds (MAE = 0.194-0.288). Such high accuracy could not be obtained by a simple method of learning from cyclic peptide data directly by lasso regression (MAE = 0.286-0.671) or ridge regression (MAE = 0.244-0.354).

CONCLUSION: In this study, we proposed a machine learning techniques that uses low-dimensional sparse modeling to predict the PPB value of cyclic peptides computationally. The low-dimensional sparse model not only exhibits excellent generalization performance but also improves interpretation of the prediction model. This can provide common an noteworthy knowledge for future cyclic peptide drug discovery studies.}, } @article {pmid30598071, year = {2018}, author = {Ma, L and Zheng, J}, title = {Single-cell gene expression analysis reveals β-cell dysfunction and deficit mechanisms in type 2 diabetes.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {515}, doi = {10.1186/s12859-018-2519-1}, pmid = {30598071}, issn = {1471-2105}, abstract = {BACKGROUND: Type 2 diabetes (T2D) is one of the most common chronic diseases. Studies on T2D are mainly built upon bulk-cell data analysis, which measures the average gene expression levels for a population of cells and cannot capture the inter-cell heterogeneity. The single-cell RNA-sequencing technology can provide additional information about the molecular mechanisms of T2D at single-cell level.

RESULTS: In this work, we analyze three datasets of single-cell transcriptomes to reveal β-cell dysfunction and deficit mechanisms in T2D. Focused on the expression levels of key genes, we conduct discrimination of healthy and T2D β-cells using five machine learning classifiers, and extracted major influential factors by calculating correlation coefficients and mutual information. Our analysis shows that T2D β-cells are normal in insulin gene expression in the scenario of low cellular stress (especially oxidative stress), but appear dysfunctional under the circumstances of high cellular stress. Remarkably, oxidative stress plays an important role in affecting the expression of insulin gene. In addition, by analyzing the genes related to apoptosis, we found that the TNFR1-, BAX-, CAPN1- and CAPN2-dependent pathways may be crucial for β-cell apoptosis in T2D. Finally, personalized analysis indicates cell heterogeneity and individual-specific insulin gene expression.

CONCLUSIONS: Oxidative stress is an important influential factor on insulin gene expression in T2D. Based on the uncovered mechanism of β-cell dysfunction and deficit, targeting key genes in the apoptosis pathway along with alleviating oxidative stress could be a potential treatment strategy for T2D.}, } @article {pmid30598070, year = {2018}, author = {Wang, Y and Wu, H and Cai, Y}, title = {A benchmark study of sequence alignment methods for protein clustering.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {529}, doi = {10.1186/s12859-018-2524-4}, pmid = {30598070}, issn = {1471-2105}, abstract = {BACKGROUND: Protein sequence alignment analyses have become a crucial step for many bioinformatics studies during the past decades. Multiple sequence alignment (MSA) and pair-wise sequence alignment (PSA) are two major approaches in sequence alignment. Former benchmark studies revealed drawbacks of MSA methods on nucleotide sequence alignments. To test whether similar drawbacks also influence protein sequence alignment analyses, we propose a new benchmark framework for protein clustering based on cluster validity. This new framework directly reflects the biological ground truth of the application scenarios that adopt sequence alignments, and evaluates the alignment quality according to the achievement of the biological goal, rather than the comparison on sequence level only, which averts the biases introduced by alignment scores or manual alignment templates. Compared with former studies, we calculate the cluster validity score based on sequence distances instead of clustering results. This strategy could avoid the influence brought by different clustering methods thus make results more dependable.

RESULTS: Results showed that PSA methods performed better than MSA methods on most of the BAliBASE benchmark datasets. Analyses on the 80 re-sampled benchmark datasets constructed by randomly choosing 90% of each dataset 10 times showed similar results.

CONCLUSIONS: These results validated that the drawbacks of MSA methods revealed in nucleotide level also existed in protein sequence alignment analyses and affect the accuracy of results.}, } @article {pmid30598069, year = {2018}, author = {Xiao, Z and Zhang, Y and Yu, R and Chen, Y and Jiang, X and Wang, Z and Li, S}, title = {In silico design of MHC class I high binding affinity peptides through motifs activation map.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {516}, doi = {10.1186/s12859-018-2517-3}, pmid = {30598069}, issn = {1471-2105}, abstract = {BACKGROUND: Finding peptides with high binding affinity to Class I major histocompatibility complex (MHC-I) attracts intensive research, and it serves a crucial part of developing a better vaccine for precision medicine. Traditional methods cost highly for designing such peptides. The advancement of computational approaches reduces the cost of new drug discovery dramatically. Compared with flourishing computational drug discovery area, the immunology area lacks tools focused on in silico design for the peptides with high binding affinity. Attributed to the ever-expanding amount of MHC-peptides binding data, it enables the tremendous influx of deep learning techniques for modeling MHC-peptides binding. To leverage the availability of these data, it is of great significance to find MHC-peptides binding specificities. The binding motifs are one of the key components to decide the MHC-peptides combination, which generally refer to a combination of some certain amino acids at certain sites which highly contribute to the binding affinity.

RESULT: In this work, we propose the Motif Activation Mapping (MAM) network for MHC-I and peptides binding to extract motifs from peptides. Then, we substitute amino acid randomly according to the motifs for generating peptides with high affinity. We demonstrated the MAM network could extract motifs which are the features of peptides of highly binding affinities, as well as generate peptides with high-affinities; that is, 0.859 for HLA-A*0201, 0.75 for HLA-A*0206, 0.92 for HLA-B*2702, 0.9 for HLA-A*6802 and 0.839 for Mamu-A1*001:01. Besides, its binding prediction result reaches the state of the art. The experiment also reveals the network is appropriate for most MHC-I with transfer learning.

CONCLUSIONS: We design the MAM network to extract the motifs from MHC-peptides binding through prediction, which are proved to generate the peptides with high binding affinity successfully. The new peptides preserve the motifs but vary in sequences.}, } @article {pmid30598068, year = {2018}, author = {Zhang, Y and Hamada, M}, title = {DeepM6ASeq: prediction and characterization of m6A-containing sequences using deep learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {524}, doi = {10.1186/s12859-018-2516-4}, pmid = {30598068}, issn = {1471-2105}, abstract = {BACKGROUND: N6-methyladensine (m6A) is a common and abundant RNA methylation modification found in various species. As a type of post-transcriptional methylation, m6A plays an important role in diverse RNA activities such as alternative splicing, an interplay with microRNAs and translation efficiency. Although existing tools can predict m6A at single-base resolution, it is still challenging to extract the biological information surrounding m6A sites.

RESULTS: We implemented a deep learning framework, named DeepM6ASeq, to predict m6A-containing sequences and characterize surrounding biological features based on miCLIP-Seq data, which detects m6A sites at single-base resolution. DeepM6ASeq showed better performance as compared to other machine learning classifiers. Moreover, an independent test on m6A-Seq data, which identifies m6A-containing genomic regions, revealed that our model is competitive in predicting m6A-containing sequences. The learned motifs from DeepM6ASeq correspond to known m6A readers. Notably, DeepM6ASeq also identifies a newly recognized m6A reader: FMR1. Besides, we found that a saliency map in the deep learning model could be utilized to visualize locations of m6A sites.

CONCULSION: We developed a deep-learning-based framework to predict and characterize m6A-containing sequences and hope to help investigators to gain more insights for m6A research. The source code is available at https://github.com/rreybeyb/DeepM6ASeq .}, } @article {pmid30598067, year = {2018}, author = {Zhang, W and Le, TD and Liu, L and Li, J}, title = {Estimating heterogeneous treatment effect by balancing heterogeneity and fitness.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {518}, doi = {10.1186/s12859-018-2521-7}, pmid = {30598067}, issn = {1471-2105}, abstract = {BACKGROUND: Estimating heterogeneous treatment effect is a fundamental problem in biological and medical applications. Recently, several recursive partitioning methods have been proposed to identify the subgroups that respond differently towards a treatment, and they rely on a fitness criterion to minimize the error between the estimated treatment effects and the unobservable ground truths.

RESULTS: In this paper, we propose that a heterogeneity criterion, which maximizes the differences of treatment effects among the subgroups, also needs to be considered. Moreover, we show that better performances can be achieved when the fitness and the heterogeneous criteria are considered simultaneously. Selecting the optimal splitting points then becomes a multi-objective problem; however, a solution that achieves optimal in both aspects are often not available. To solve this problem, we propose a multi-objective splitting procedure to balance both criteria. The proposed procedure is computationally efficient and fits naturally into the existing recursive partitioning framework. Experimental results show that the proposed multi-objective approach performs consistently better than existing ones.

CONCLUSION: Heterogeneity should be considered with fitness in heterogeneous treatment effect estimation, and the proposed multi-objective splitting procedure achieves the best performance by balancing both criteria.}, } @article {pmid30598066, year = {2018}, author = {Ma, Y and Yu, Z and Han, G and Li, J and Anh, V}, title = {Identification of pre-microRNAs by characterizing their sequence order evolution information and secondary structure graphs.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {521}, doi = {10.1186/s12859-018-2518-2}, pmid = {30598066}, issn = {1471-2105}, abstract = {BACKGROUND: Distinction between pre-microRNAs (precursor microRNAs) and length-similar pseudo pre-microRNAs can reveal more about the regulatory mechanism of RNA biological processes. Machine learning techniques have been widely applied to deal with this challenging problem. However, most of them mainly focus on secondary structure information of pre-microRNAs, while ignoring sequence-order information and sequence evolution information.

RESULTS: We use new features for the machine learning algorithms to improve the classification performance by characterizing both sequence order evolution information and secondary structure graphs. We developed three steps to extract these features of pre-microRNAs. We first extract features from PSI-BLAST profiles and Hilbert-Huang transforms, which contain rich sequence evolution information and sequence-order information respectively. We then obtain properties of small molecular networks of pre-microRNAs, which contain refined secondary structure information. These structural features are carefully generated so that they can depict both global and local characteristics of pre-microRNAs. In total, our feature space covers 591 features. The maximum relevance and minimum redundancy (mRMR) feature selection method is adopted before support vector machine (SVM) is applied as our classifier. The constructed classification model is named MicroRNA -NHPred. The performance of MicroRNA -NHPred is high and stable, which is better than that of those state-of-the-art methods, achieving an accuracy of up to 94.83% on same benchmark datasets.

CONCLUSIONS: The high prediction accuracy achieved by our proposed method is attributed to the design of a comprehensive feature set on the sequences and secondary structures, which are capable of characterizing the sequence evolution information and sequence-order information, and global and local information of pre-microRNAs secondary structures. MicroRNA -NHPred is a valuable method for pre-microRNAs identification. The source codes of our method can be downloaded from https://github.com/myl446/MicroRNA-NHPred .}, } @article {pmid30598065, year = {2018}, author = {Zheng, Y and Peng, H and Zhang, X and Zhao, Z and Yin, J and Li, J}, title = {Predicting adverse drug reactions of combined medication from heterogeneous pharmacologic databases.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 19}, pages = {517}, doi = {10.1186/s12859-018-2520-8}, pmid = {30598065}, issn = {1471-2105}, abstract = {BACKGROUND: Early and accurate identification of potential adverse drug reactions (ADRs) for combined medication is vital for public health. Existing methods either rely on expensive wet-lab experiments or detecting existing associations from related records. Thus, they inevitably suffer under-reporting, delays in reporting, and inability to detect ADRs for new and rare drugs. The current application of machine learning methods is severely impeded by the lack of proper drug representation and credible negative samples. Therefore, a method to represent drugs properly and to select credible negative samples becomes vital in applying machine learning methods to this problem.

RESULTS: In this work, we propose a machine learning method to predict ADRs of combined medication from pharmacologic databases by building up highly-credible negative samples (HCNS-ADR). Specifically, we fuse heterogeneous information from different databases and represent each drug as a multi-dimensional vector according to its chemical substructures, target proteins, substituents, and related pathways first. Then, a drug-pair vector is obtained by appending the vector of one drug to the other. Next, we construct a drug-disease-gene network and devise a scoring method to measure the interaction probability of every drug pair via network analysis. Drug pairs with lower interaction probability are preferentially selected as negative samples. Following that, the validated positive samples and the selected credible negative samples are projected into a lower-dimensional space using the principal component analysis. Finally, a classifier is built for each ADR using its positive and negative samples with reduced dimensions. The performance of the proposed method is evaluated on simulative prediction for 1276 ADRs and 1048 drugs, comparing using four machine learning algorithms and with two baseline approaches. Extensive experiments show that the proposed way to represent drugs characterizes drugs accurately. With highly-credible negative samples selected by HCNS-ADR, the four machine learning algorithms achieve significant performance improvements. HCNS-ADR is also shown to be able to predict both known and novel drug-drug-ADR associations, outperforming two other baseline approaches significantly.

CONCLUSIONS: The results demonstrate that integration of different drug properties to represent drugs are valuable for ADR prediction of combined medication and the selection of highly-credible negative samples can significantly improve the prediction performance.}, } @article {pmid30597559, year = {2018}, author = {Rodríguez-Muñoz, R and Boonekamp, JJ and Liu, XP and Skicko, I and Fisher, DN and Hopwood, P and Tregenza, T}, title = {Testing the effect of early-life reproductive effort on age-related decline in a wild insect.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13679}, pmid = {30597559}, issn = {1558-5646}, support = {//Leverhulme Trust/ ; NE/E005403/1//Natural Environment Research Council/ ; NE/H02249X/1//Natural Environment Research Council/ ; NE/H02364X/1//Natural Environment Research Council/ ; NE/L003635/1//Natural Environment Research Council/ ; NE/R000328/1//Natural Environment Research Council/ ; CONSENT 792215//European Union's Horizon 2020/ ; }, abstract = {The disposable soma theory of ageing predicts that when organisms invest in reproduction they do so by reducing their investment in body maintenance, inducing a trade-off between reproduction and survival. Experiments on invertebrates in the lab provide support for the theory by demonstrating the predicted responses to manipulation of reproductive effort or lifespan. However, experimental studies in birds and evidence from observational (nonmanipulative) studies in nature do not consistently reveal trade-offs. Most species studied previously in the wild are mammals and birds that reproduce over multiple discrete seasons. This contrasts with temperate invertebrates, which typically have annual generations and reproduce over a single season. We expand the taxonomic range of senescence study systems to include life histories typical of most temperate invertebrates. We monitored reproductive effort, ageing, and survival in a natural field cricket population over ten years to test the prediction that individuals investing more in early-reproduction senesce faster and die younger. We found no evidence of a trade-off between early-life reproductive effort and survival, and only weak evidence for a trade-off with phenotypic senescence. We discuss the possibility that organisms with multiple discrete breeding seasons may have greater opportunities to express trade-offs between reproduction and senescence.}, } @article {pmid30597557, year = {2018}, author = {Lipshutz, SE and Meier, JI and Derryberry, GE and Miller, MJ and Seehausen, O and Derryberry, EP}, title = {Differential introgression of a female competitive trait in a hybrid zone between sex-role reversed species.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13675}, pmid = {30597557}, issn = {1558-5646}, support = {Stone Center//Tulane University/ ; Tinker Foundation//Tulane University/ ; Alexander Wetmore Memorial Research Award//American Ornithologists' Union/ ; NSF EPSCoR LINK Grant No. 177//Louisiana Board of Regents/ ; Frank M. Chapman Memorial Grant//American Museum of Natural History/ ; 1154145//National Science Foundation/ ; 1818235//National Science Foundation/ ; Young Explorer Grant//National Geographic Society/ ; }, abstract = {Mating behavior between recently diverged species in secondary contact can impede or promote reproductive isolation. Traditionally, researchers focus on the importance of female mate choice and male-male competition in maintaining or eroding species barriers. Although female-female competition is widespread, little is known about its role in the speciation process. Here, we investigate a case of interspecific female competition and its influence on patterns of phenotypic and genetic introgression between species. We examine a hybrid zone between sex-role reversed, Neotropical shorebird species, the northern jacana (Jacana spinosa) and wattled jacana (J. jacana), in which female-female competition is a major determinant of reproductive success. Previous work found that females of the more aggressive and larger species, J. spinosa, disproportionately mother hybrid offspring, potentially by monopolizing breeding territories in sympatry with J. jacana. We find a cline shift of female body mass relative to the genetic center of the hybrid zone, consistent with asymmetric introgression of this competitive trait. We suggest that divergence in sexual characteristics between sex-role reversed females can influence patterns of gene flow upon secondary contact, similar to males in systems with more typical sex roles.}, } @article {pmid30597556, year = {2018}, author = {Morris, MRJ and Kaufman, R and Rogers, SM}, title = {Heterozygosity and asymmetry: Ectodysplasin as a form of genetic stress in marine threespine stickleback.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13678}, pmid = {30597556}, issn = {1558-5646}, support = {SMR//NSERC Discovery Grant/ ; RT735287//NSERC Discovery Grant/ ; //Killam Trusts/ ; }, abstract = {Genome-wide heterozygosity has long been hypothesized to play a role in buffering organisms against developmental perturbations, potentially resulting in increased symmetry. If true, this could in part explain the maintenance of standing genetic variation in wild populations. Marine threespine sticklebacks (Gasterosteus aculeatus) were sampled across their eastern Pacific coastal distribution from Alaska to California and variations in asymmetry for both structural and nonstructural armor traits (lateral plates) were assessed. Structural plates consistently showed less asymmetry than nonstructural plates, but standardized measures of heterozygosity were not correlated with the extent of asymmetry expressed by a fish. Fish that were heterozygous for the major-effect gene controlling lateral plate variation (Ectodysplasin) had higher occurrences of asymmetry, even when the individuals were phenotypically fully plated. Collectively, this suggests that heterozygosity at a major-effect locus can have a greater impact on asymmetry than heterozygosity sampled across the genome.}, } @article {pmid30597549, year = {2018}, author = {Albrecht, T and Opletalová, K and Reif, J and Janoušek, V and Piálek, L and Cramer, ERA and Johnsen, A and Reifová, R}, title = {Sperm divergence in a passerine contact zone: Indication of reinforcement at the gametic level.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13677}, pmid = {30597549}, issn = {1558-5646}, support = {213592v//Norwegian Research Council/ ; PRIMUS/19/SCI/08//Charles University/ ; 15-10884Y//Grantová Agentura České Republiky/ ; 18-14325S//Grantová Agentura České Republiky/ ; }, abstract = {Postcopulatory sexual selection may promote evolutionary diversification in sperm form, but the contribution of between-species divergence in sperm morphology to the origin of reproductive isolation and speciation remains little understood. To assess the possible role of sperm diversification in reproductive isolation, we studied sperm morphology in two closely related bird species, the common nightingale (Luscinia megarhynchos) and the thrush nightingale (Luscinia luscinia), that hybridize in a secondary contact zone spanning Central and Eastern Europe. We found: (1) striking divergence between the species in total sperm length, accompanied by a difference in the length of the mitochondrial sperm component; (2) greater divergence between species in sperm morphology in sympatry than in allopatry, with evidence for character displacement in sperm head length detected in L. megarhynchos; (3) interspecific hybrids showing sperm with a length intermediate between the parental species, but no evidence for decreased sperm quality (the proportion of abnormal spermatozoa in ejaculates). Our results demonstrate that divergence in sperm morphology between the two nightingale species does not result in intrinsic postzygotic isolation, but may contribute to postcopulatory prezygotic isolation. This isolation could be strengthened in sympatry by reinforcement.}, } @article {pmid30597539, year = {2018}, author = {Rodríguez-Muñoz, R and Boonekamp, JJ and Liu, XP and Skicko, I and Haugland Pedersen, S and Fisher, DN and Hopwood, P and Tregenza, T}, title = {Comparing individual and population measures of senescence across 10 years in a wild insect population.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13674}, pmid = {30597539}, issn = {1558-5646}, support = {792215//European Union's Horizon 2020 research and innovation program/ ; NE/E005403/1//Natural Environment Research Council/ ; NE/H02249X/1//Natural Environment Research Council/ ; NE/H02364X/1//Natural Environment Research Council/ ; NE/L003635/1//Natural Environment Research Council/ ; NE/R000328/1//Natural Environment Research Council/ ; //Leverhulme Trust/ ; }, abstract = {Declines in survival and performance with advancing age (senescence) have been widely documented in natural populations, but whether patterns of senescence across traits reflect a common underlying process of biological ageing remains unclear. Senescence is typically characterized via assessments of the rate of change in mortality with age (actuarial senescence) or the rate of change in phenotypic performance with age (phenotypic senescence). Although both phenomena are considered indicative of underlying declines in somatic integrity, whether actuarial and phenotypic senescence rates are actually correlated has yet to be established. Here we present evidence of both actuarial and phenotypic senescence from a decade-long longitudinal field study of wild insects. By tagging every individual and using continuous video monitoring with a network of up to 140 video cameras, we were able to record survival and behavioral data on an entire adult population of field crickets. This reveals that both actuarial and phenotypic senescence vary substantially across 10 annual generations. This variation allows us to identify a strong correlation between actuarial and phenotypic measures of senescence. Our study demonstrates age-related phenotypic declines reflected in population level mortality rates and reveals that observations of senescence in a single year may not be representative of a general pattern.}, } @article {pmid30597011, year = {2018}, author = {Kurafeiski, JD and Pinto, P and Bornberg-Bauer, E}, title = {Evolutionary potential of cis-regulatory mutations to cause rapid changes in transcription factor binding.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evy269}, pmid = {30597011}, issn = {1759-6653}, abstract = {Transcriptional regulation is crucial for all biological processes and well investigated at the molecular level for a wide range of organisms. However, it is quite unclear how innovations, such as the activity of a novel regulatory element, evolve. In the case of transcription factor (TF) binding, both a novel TF and a novel binding site would need to evolve concertedly. Since promiscuous functions have recently been identified as important intermediate steps in creating novel specific function in many areas such as enzyme evolution and protein-protein interactions, we ask here how promiscuous binding of TFs to transcription factor binding sites (TFBSs) affects the robustness and evolvability of this tightly regulated system. Specifically, we investigate the binding behaviour of several hundred TFs from different species at unprecedented breadth.Our results illustrate multiple aspects of TF binding interactions, ranging from correlations between the strength of the interaction bond and specificity, to preferences regarding TFBS nucleotide composition in relation to both domains and binding specificity.We identified a subset of high A/T binding motifs. Motifs in this subset had many functionally neutral 1-error mutants, and were bound by multiple different binding domains. Our results indicate that, especially for some TF-TFBS associations, low binding specificity confers high degrees of evolvability, i.e. that few mutations facilitate rapid changes in transcriptional regulation, in particular for large and old TF families. In this study we identify binding motifs exhibiting behaviour indicating high evolutionary potential for innovations in transcriptional regulation.}, } @article {pmid30595840, year = {2018}, author = {Bentley, GR}, title = {Editorial comment: Pre-eclampsia.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {295-296}, doi = {10.1093/emph/eoy030}, pmid = {30595840}, issn = {2050-6201}, } @article {pmid30595792, year = {2018}, author = {Elliott, SL}, title = {From the Editor-in-Chief: Reflection and Renewal.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, doi = {10.1128/jmbe.v20i1.1713}, pmid = {30595792}, issn = {1935-7877}, } @article {pmid30595791, year = {2018}, author = {Weatherbee, RA and Lindsay, SM}, title = {Designing a Curriculum-Aligned Assessment of Cumulative Learning about Marine Primary Production to Improve an Undergraduate Marine Sciences Program.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, doi = {10.1128/jmbe.v19i3.1396}, pmid = {30595791}, issn = {1935-7877}, abstract = {We developed an assessment to track changes in understanding about marine primary production, a key concept taught across our undergraduate curriculum. Question content was informed by investigating student misunderstandings, conducting faculty interviews, and mapping primary production concepts to the curriculum. Content questions were paired with questions asking students how confident they were in their answers. Although students gained knowledge of marine primary production across educational levels, confidence data and item analysis indicated student misunderstandings on several concepts. Many students had difficulty on questions that required interpreting graphs or other higher-order thinking skills. The results set the stage for additional focused assessment and curriculum revision, and the questions may be useful in developing a large-scale, interdisciplinary marine sciences concept inventory.}, } @article {pmid30595790, year = {2018}, author = {Marbach-Ad, G and Marr, J}, title = {Enhancing Graduate Students' Ability to Conduct and Communicate Research through an Interdisciplinary Lens.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, doi = {10.1128/jmbe.v19i3.1592}, pmid = {30595790}, issn = {1935-7877}, abstract = {This research is a part of a longitudinal study of the Computation and Mathematics for Biological Networks (COMBINE) program at the University of Maryland. The mission of COMBINE is to train doctoral students from a wide range of fields to pursue interdisciplinary research. Here, we focus on one component of COMBINE, a semester-long course titled Data Practicum at the Intersection of the Physical, Computer, and Life Sciences. The goal of this study was to explore the effectiveness of the teaching practices that were used in the Data Practicum. We investigated their impact on graduate students' confidence to conduct research through an interdisciplinary lens and to communicate their research to diverse audiences. We used validated pre- and post-course online surveys, in-class observations, collection of artifacts, and interviews. Interviewed students and instructors highlighted the course's iterative process, peer review system, and unique incorporation of outside research already being conducted by students as the most impactful aspects of the course. Based on students' reports and artifacts, the Data Practicum was successful in helping them to communicate their research visually, orally, and in text to a wide and varied audience, to critically review others' work, inside and outside their discipline, and to develop awareness of research in other disciplines. We observed that it is possible to enhance interdisciplinary communication skills through an iterative teaching approach that gives students a chance to incorporate feedback from multiple sources. This course could serve as a model for other graduate programs wishing to increase training in interdisciplinary skills.}, } @article {pmid30595789, year = {2018}, author = {Loberti, AM and Dewsbury, BM}, title = {Using a Logic Model to Direct Backward Design of Curriculum.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, doi = {10.1128/jmbe.v19i3.1638}, pmid = {30595789}, issn = {1935-7877}, abstract = {Contemporary approaches to STEM course design typically encourage the backward design of curricula. This is to say that the learning activities and assessments of the course are explicitly guided by the learning outcomes of the course. Less discussed is the fact that this paradigm is also used in nonacademic settings. From this perspective, drawing from the nonacademic world, we discuss the use of a logic model approach as a structured, orderly way to implement backward design. We use the design and implementation of an introductory biology class to illustrate how a logic model template helped frame our inclusive, Freirean approach to teaching and learning.}, } @article {pmid30595788, year = {2018}, author = {Egusa, EA and Edwards, DJ and Thao, ML and Kirk, LL and Hanne, LF}, title = {Isolation and Characterization of Bacteria that Produce Polyhydroxybutyrate Depolymerases.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, doi = {10.1128/jmbe.v19i3.1682}, pmid = {30595788}, issn = {1935-7877}, } @article {pmid30595787, year = {2018}, author = {Mosovsky, K}, title = {The Use of a Fast-Paced, Competitive Drawing Game as a Student-Approved Review Strategy for Microbiology.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, doi = {10.1128/jmbe.v19i3.1691}, pmid = {30595787}, issn = {1935-7877}, } @article {pmid30595613, year = {2018}, author = {Ludwig, D and Poliseli, L}, title = {Relating traditional and academic ecological knowledge: mechanistic and holistic epistemologies across cultures.}, journal = {Biology & philosophy}, volume = {33}, number = {5}, pages = {43}, doi = {10.1007/s10539-018-9655-x}, pmid = {30595613}, issn = {0169-3867}, abstract = {Current debates about the integration of traditional and academic ecological knowledge (TEK and AEK) struggle with a dilemma of division and assimilation. On the one hand, the emphasis on differences between traditional and academic perspectives has been criticized as creating an artificial divide that brands TEK as "non-scientific" and contributes to its marginalization. On the other hand, there has been increased concern about inadequate assimilation of Indigenous and other traditional perspectives into scientific practices that disregards the holistic nature and values of TEK. The aim of this article is to develop a practice-based account of the epistemic relations between TEK and AEK that avoids both horns of the dilemma. While relations between TEK and AEK are often described in terms of the "holistic" nature of the former and the "mechanistic" character of the latter, we argue that a simple holism-mechanism divide misrepresents the epistemic resources of both TEK and AEK. Based on the literature on mechanistic explanations in philosophy of science, we argue that holders of TEK are perfectly capable of identifying mechanisms that underlie ecological phenomena while AEK often relies on non-mechanistic strategies of dealing with ecological complexity. Instead of generic characterizations of knowledge systems as either mechanistic or holistic, we propose to approach epistemic relations between knowledge systems by analyzing their (partly mechanistic and partly holistic) heuristics in practice.}, } @article {pmid30595612, year = {2018}, author = {Hopster, J}, title = {Evolutionary arguments against moral realism: Why the empirical details matter (and which ones do).}, journal = {Biology & philosophy}, volume = {33}, number = {5}, pages = {41}, doi = {10.1007/s10539-018-9652-0}, pmid = {30595612}, issn = {0169-3867}, abstract = {The aim of this article is to identify the strongest evolutionary debunking argument (EDA) against moral realism and to assess on which empirical assumptions it relies. In the recent metaethical literature, several authors have de-emphasized the evolutionary component of EDAs against moral realism: presumably, the success or failure of these arguments is largely orthogonal to empirical issues. I argue that this claim is mistaken. First, I point out that Sharon Street's and Michael Ruse's EDAs both involve substantive claims about the evolution of our moral judgments. Next, I argue that combining their respective evolutionary claims can help debunkers to make the best empirical case against moral realism. Some realists have argued that the very attempt to explain the contents of our endorsed moral judgments in evolutionary terms is misguided, and have sought to escape EDAs by denying their evolutionary premise. But realists who pursue this reply can still be challenged on empirical grounds: debunkers may argue that the best, scientifically informed historical explanations of our moral endorsements do not involve an appeal to mind-independent truths. I conclude, therefore, that the empirical considerations relevant for the strongest empirically driven argument against moral realism go beyond the strictly evolutionary realm; debunkers are best advised to draw upon other sources of genealogical knowledge as well.}, } @article {pmid30595467, year = {2018}, author = {Maier, AG and Matuschewski, K and Zhang, M and Rug, M}, title = {Plasmodium falciparum.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.010}, pmid = {30595467}, issn = {1471-5007}, abstract = {Plasmodium falciparum is the etiological agent of malaria tropica, the leading cause of death due to a vector-borne infectious disease, claiming 0.5 million lives every year. The single-cell eukaryote undergoes a complex life cycle and is an obligate intracellular parasite of hepatocytes (clinically silent) and erythrocytes (disease causing). An infection can progress to a wide range of pathologies, including severe anemia and cerebral malaria, which can lead to death. P. falciparum repeatedly replicates over the course of 48h inside erythrocytes, resulting in exponential growth and rapid disease progression. As the single most important infectious disease afflicting children, no other pathogen has exerted a higher selection pressure on the human genome. Over 20 polymorphisms, including the sickle-cell trait, have been selected in human populations, despite severe fitness costs, since they offer protection against fatal P. falciparum infections. No effective vaccine exists, but several curative treatments are available.}, } @article {pmid30595401, year = {2019}, author = {Qi, H and Price, BD and Day, TA}, title = {Multiple Roles for Mono- and Poly(ADP-Ribose) in Regulating Stress Responses.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {159-172}, doi = {10.1016/j.tig.2018.12.002}, pmid = {30595401}, issn = {0168-9525}, support = {K01 AG056554/AG/NIA NIH HHS/United States ; R01 CA064585/CA/NCI NIH HHS/United States ; R01 CA177884/CA/NCI NIH HHS/United States ; }, abstract = {Although stress-induced synthesis of mono(ADP-ribose) (mADPr) and poly(ADP-ribose) (pADPr) conjugates by pADPr polymerase (PARP) enzymes has been studied extensively, the removal and degradation of pADPr, as well as the fate of ADPr metabolites, have received less attention. The observations that stress-induced pADPr undergoes rapid turnover, and that deficiencies in ADPr degradation phenocopy loss of pADPr synthesis, suggest that ADPr degradation is fundamentally important to the cellular stress response. Recent work has identified several distinct families of pADPr hydrolases that can degrade pADPr to release pADPr or mADPr into the cytoplasm. Further, many stress-response proteins contain ADPr-binding domains that can interact with these metabolites. We discuss how pADPr metabolites generated during pADPr degradation can function as signaling intermediates in processes such as inflammation, apoptosis, and DNA damage responses. These studies highlight that the full cycle of ADPr metabolism, including both synthesis and degradation, is necessary for responses to genotoxic stress.}, } @article {pmid30595333, year = {2018}, author = {Rinkevich, B}, title = {The tail of the underwater phoenix.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.015}, pmid = {30595333}, issn = {1095-564X}, } @article {pmid30594734, year = {2018}, author = {Pichardo-Marcano, FJ and Nieto-Blázquez, ME and MacDonald, AN and Galeano, G and Roncal, J}, title = {Phylogeny, historical biogeography and diversification rates in an economically important group of Neotropical palms: Tribe Euterpeae.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {67-81}, doi = {10.1016/j.ympev.2018.12.030}, pmid = {30594734}, issn = {1095-9513}, abstract = {Tribe Euterpeae is an economically and ecologically important group of Neotropical palms (Arecaceae). Some species are hyperdominant in the Neotropics, and many constitute a good source of revenue. To reconstruct the biogeographical history and diversification of the Euterpeae, we inferred a robust dated molecular phylogenetic hypothesis including 82% of the species sequenced for five DNA regions (trnD-trnT, CISP4, WRKY6, RPB2, and PHYB). Ancestral range was estimated using all models available in BioGeoBEARS and Binary State Speciation and Extinction analysis was used to evaluate the association of biome and inflorescence type with diversification rates. All intergeneric relationships were resolved providing insight on the taxonomic controversy of Jessenia, Euterpe and Prestoea. Three widely distributed Neotropical species were non-monophyletic, inviting a revision of species circumscriptions. The Euterpeae started its diversification in the mid Eocene (40 Mya), with most species-level divergence events occurring in the last 10 million years. Four colonization events from Central to South America were inferred. Different diversification rates were associated with biomes. Lowland rainforest was inferred as the ancestral biome of Euterpeae, attesting to the importance of lowland adapted lineages on the assembly of the montane flora. The two-fold higher speciation rate for montane taxa (compared with lowland rainforest taxa) was contemporaneous to the Andean orogenic uplift. The specialized beetle pollination of Oenocarpus with its hippuriform (horsetail shape) inflorescence was not associated with diversification rates in Euterpeae.}, } @article {pmid30594733, year = {2018}, author = {Guo, P and Liu, Q and Zhu, F and Zhong, GH and Che, J and Wang, P and Xie, YL and Murphy, RW and Malhotra, A}, title = {Multilocus phylogeography of the brown-spotted pitviper Protobothrops mucrosquamatus (Reptilia: Serpentes: Viperidae) sheds a new light on the diversification pattern in Asia.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {82-91}, doi = {10.1016/j.ympev.2018.12.028}, pmid = {30594733}, issn = {1095-9513}, abstract = {Understanding the influence of geographical events and climate changes on genetic diversity is essential in explaining current patterns of genetic structure and geographic distribution of organisms. We inferred phylogenetic relationships, investigated historical demography, explored the evolutionary history, and clarified intraspecific taxonomy of Protobothrops mucrosquamatus, which is one of the commonest and most wide-ranging Asian pitvipers. A total of 184 samples from 54 localities were sequenced and analyzed for two mitochondrial gene fragments and two nuclear genes. Phylogenetic reconstruction based on mtDNA sequences revealed the existence of a minimum of five geographically structured and well-supported lineages within P. mucrosquamatus. Based on the mtDNA gene tree, and the geographic relationship between populations allied by matrilineal lineages, a complex longitudinal and latitudinal diversification pattern was uncovered in P. mucrosquamatus. The estimated date of the origin of the species (about 5.3 Ma) and divergence of the intraspecific lineages match the rapid uplifting of Qinghai-Xizang Plateau, and is also consistent with those of some other co-distributed Asian pitvipers. Formation of the two island lineages (Taiwan and Hainan) was generally congruent with the first isolation of the islands, but the two lineages showed different relationships with the continental Asian populations in comparison with some other pitvipers. Population historical demographic analyses, based on three methods, showed that all lineages have experienced slight population expansion in and around the Dali Glacial. Tests of intraspecific taxonomy indicated that no cryptic taxon is present within this widely distributed snake.}, } @article {pmid30594633, year = {2018}, author = {Yan, X and Tao, J and Luo, HL and Tan, LT and Rong, W and Li, HP and He, CZ}, title = {A type III effector XopLXcc8004 is vital for Xanthomonas campestris pathovar campestris to regulate plant immunity.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.12.001}, pmid = {30594633}, issn = {1769-7123}, abstract = {Xanthomonas campestris pv. campestris (Xcc) secretes a suite of effectors into host plants via the type III secretion system (T3SS), modulating plant immunity defenses. Strain Xcc8004 causes black rot in brassica plants, including Arabidopsis thaliana, making it a classical model for the study of Xanthomonas pathogenesis. XopLXcc8004 was defined as a T3SS effector (T3SE) since its homologues XopLXcv85-10 from Xanthomonas campestris pv. vesicatoria (Xcv85-10) contribute to virulence in host plants. Except for its virulence on Chinese radish plants, little was previously known about the regulation and function of XopLXcc8004. Here, we tested the role of XopLXcc8004 in the pathogenicity of Xcc8004 on different host plants including Arabidopsis. We found that it was required for full virulence of Xcc8004 in Chinese cabbage. XopLXcc8004 promoted bacterial infection in Arabidopsis and suppressed bacterial flagellin (flg22)-induced FRK1 transcription, reactive oxygen species (ROS) burst, callose deposition, and pathogenesis-related marker gene expression, but it did not affect mitogen-activated protein kinases (MAPKs) cascade. Early and prolonged expression of XopLXcc8004 affected Arabidopsis growth and development. We demonstrated that XopLXcc8004 is a virulence factor and interferes with innate immunity of Arabidopsis by suppressing pathogen-associated molecular pattern-triggered immunity (PTI) signaling, independent of MAPKs.}, } @article {pmid30594505, year = {2018}, author = {Garcia-Moreno, SA and Futtner, CR and Salamone, IM and Gonen, N and Lovell-Badge, R and Maatouk, DM}, title = {Gonadal supporting cells acquire sex-specific chromatin landscapes during mammalian sex determination.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.023}, pmid = {30594505}, issn = {1095-564X}, support = {T32 DK007169/DK/NIDDK NIH HHS/United States ; T32 GM008061/GM/NIGMS NIH HHS/United States ; }, abstract = {Cis-regulatory elements are critical for the precise spatiotemporal regulation of genes during development. However, identifying functional regulatory sites that drive cell differentiation in vivo has been complicated by the high numbers of cells required for whole-genome epigenetic assays. Here, we identified putative regulatory elements during sex determination by performing ATAC-seq and ChIP-seq for H3K27ac in purified XX and XY gonadal supporting cells before and after sex determination in mice. We show that XX and XY supporting cells initiate sex determination with similar chromatin landscapes and acquire sex-specific regulatory elements as they commit to the male or female fate. To validate our approach, we identified a functional gonad-specific enhancer downstream of Bmp2, an ovary-promoting gene. This work increases our understanding of the complex regulatory network underlying mammalian sex determination and provides a powerful resource for identifying non-coding regulatory elements that could harbor mutations that lead to Disorders of Sexual Development.}, } @article {pmid30594504, year = {2018}, author = {Negi, S and Bolt, CC and Zhang, H and Stubbs, L}, title = {An extended regulatory landscape drives Tbx18 activity in a variety of prostate-associated cell lineages.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.11.023}, pmid = {30594504}, issn = {1095-564X}, support = {R01 DK095685/DK/NIDDK NIH HHS/United States ; }, abstract = {The evolutionarily conserved transcription factor, Tbx18, is expressed in a dynamic pattern throughout embryonic and early postnatal life and plays crucial roles in the development of multiple organ systems. Previous studies have indicated that this dynamic function is controlled by an expansive regulatory structure, extending far upstream and downstream of the gene. With the goal of identifying elements that interact with the Tbx18 promoter in developing prostate, we coupled chromatin conformation capture (4C) and ATAC-seq from embryonic day 18.5 (E18.5) mouse urogenital sinus (UGS), where Tbx18 is highly expressed. The data revealed dozens of active chromatin elements distributed throughout a 1.5 million base pair topologically associating domain (TAD). To identify cell types contributing to this chromatin signal, we used lineage tracing methods with a Tbx18 Cre "knock-in" allele; these data show clearly that Tbx18-expressing precursors differentiate into wide array of cell types in multiple tissue compartments, most of which have not been previously reported. We also used a 209 kb Cre-expressing Tbx18 transgene, to partition enhancers for specific precursor types into two rough spatial domains. Within this central 209 kb compartment, we identified ECR1, previously described to regulate Tbx18 expression in ureter, as an active regulator of UGS expression. Together these data define the diverse fates of Tbx18+ precursors in prostate-associated tissues for the first time, and identify a highly active TAD controlling the gene's essential function in this tissue.}, } @article {pmid30594415, year = {2018}, author = {Tadesse, FG and Meerstein-Kessel, L and Gonçalves, BP and Drakeley, C and Ranford-Cartwright, L and Bousema, T}, title = {Gametocyte Sex Ratio: The Key to Understanding Plasmodium falciparum Transmission?.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.12.001}, pmid = {30594415}, issn = {1471-5007}, abstract = {A mosquito needs to ingest at least one male and one female gametocyte to become infected with malaria. The sex of Plasmodium falciparum gametocytes can be determined microscopically but recent transcriptomics studies paved the way for the development of molecular methods that allow sex-ratio assessments at much lower gametocyte densities. These sex-specific gametocyte diagnostics were recently used to examine gametocyte dynamics in controlled and natural infections as well as the impact of different antimalarial drugs. It is currently unclear to what extent sex-specific gametocyte diagnostics obviate the need for mosquito feeding assays to formally assess transmission potential. Here, we review recent and historic assessments of gametocyte sex ratio in relation to host and parasite characteristics, treatment, and transmission potential.}, } @article {pmid30594412, year = {2018}, author = {Tee, SH}, title = {Fictional experimental modeling in biology: In vivo representation.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.shpsc.2018.12.001}, pmid = {30594412}, issn = {1879-2499}, abstract = {It is commonly held that in vivo biological experimental models are concrete and non-fictional. This belief is primarily supported by the fact that in vivo studies involve biological models which are alive, and what is alive cannot be fictional. However, I argue that this is not always the case. The design of an experimental model could still render an in vivo model fictional because fictional elements and processes can be built into these in vivo experimental models. These fictional elements are essential parts of a credentialed fiction because the designs of in vivo experimental models are constrained by imaginability, conceivability, and credit-worthiness. Therefore, despite its fictionality, it is credible for an in vivo experimental model to stand in for the phenomenon of interest.}, } @article {pmid30594323, year = {2018}, author = {Puts, DA and Aung, T}, title = {Does Men's Voice Pitch Signal Formidability? A Reply to Feinberg et al.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2018.12.004}, pmid = {30594323}, issn = {1872-8383}, } @article {pmid30594317, year = {2018}, author = {Rossie, JB and Hill, A}, title = {Corrigendum to "A new species of Simiolus from the middle Miocene of the Tugen Hills, Kenya" [Journal of Human Evolution 125 (2018) 50-58].}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2018.12.006}, pmid = {30594317}, issn = {1095-8606}, } @article {pmid30594246, year = {2018}, author = {Saeed, MT and Ahmad, J and Baumbach, J and Pauling, J and Shafi, A and Paracha, RZ and Hayat, A and Ali, A}, title = {Parameter estimation of qualitative biological regulatory networks on high performance computing hardware.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {146}, doi = {10.1186/s12918-018-0670-y}, pmid = {30594246}, issn = {1752-0509}, abstract = {BACKGROUND: Biological Regulatory Networks (BRNs) are responsible for developmental and maintenance related functions in organisms. These functions are implemented by the dynamics of BRNs and are sensitive to regulations enforced by specific activators and inhibitors. The logical modeling formalism by René Thomas incorporates this sensitivity with a set of logical parameters modulated by available regulators, varying with time. With the increase in complexity of BRNs in terms of number of entities and their interactions, the task of parameters estimation becomes computationally expensive with existing sequential SMBioNET tool. We extend the existing sequential implementation of SMBioNET by using a data decomposition approach using a Java messaging library called MPJ Express. The approach divides the parameters space into different regions and each region is then explored in parallel on High Performance Computing (HPC) hardware.

RESULTS: The performance of the parallel approach is evaluated on BRNs of different sizes, and experimental results on multicore and cluster computers showed almost linear speed-up. This parallel code can be executed on a wide range of concurrent hardware including laptops equipped with multicore processors, and specialized distributed memory computer systems. To demonstrate the application of parallel implementation, we selected a case study of Hexosamine Biosynthetic Pathway (HBP) in cancer progression to identify potential therapeutic targets against cancer. A set of logical parameters were computed for HBP model that directs the biological system to a state of recovery. Furthermore, the parameters also suggest a potential therapeutic intervention that restores homeostasis. Additionally, the performance of parallel application was also evaluated on a network (comprising of 23 entities) of Fibroblast Growth Factor Signalling in Drosophila melanogaster.

CONCLUSIONS: Qualitative modeling framework is widely used for investigating dynamics of biological regulatory networks. However, computation of model parameters in qualitative modeling is computationally intensive. In this work, we presented results of our Java based parallel implementation that provides almost linear speed-up on both multicore and cluster platforms. The parallel implementation is available at https://psmbionet.github.io .}, } @article {pmid30594152, year = {2018}, author = {Wu, X and Xu, FL and Ding, M and Zhang, JJ and Yao, J and Wang, BJ}, title = {Characterization and functional analyses of the human HTR1A gene: 5' regulatory region modulates gene expression in vitro.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {115}, doi = {10.1186/s12863-018-0708-6}, pmid = {30594152}, issn = {1471-2156}, support = {81601653//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The serotonin neurotransmitter (5-HT) and its receptors have important roles in neuropsychiatric disorders such as schizophrenia. The aim of this study was to investigate the functional sequences of the 5' regulation region of the human HTR1A gene to explore the effects on the expression of the 5-HT1A receptor.

METHODS: Fourteen recombinant pGL3-basic vectors containing deletion fragments of the HTR1A gene regulatory region were transfected with HEK-293 and SK-N-SH cells. The relative chemiluminescence intensities of different length fragments were analyzed. The JASPAR software was used for the prediction of transcription factors.

RESULTS: In the HEK-293 cells, the relative chemiluminescence intensity of the - 1649 bp to - 1550 bp (ATG + 1) fragment was significantly different. Two inhibitory activity regions were found in the - 1409 bp to - 1381 bp and - 1196 bp to - 1124 bp fragments, which might be bound to the GATA or SOX10 transcription factors as predicted by the JASPAR software. In addition, the fragments located from - 1124 bp to - 1064 bp and from - 908 bp to - 722 bp up-regulated protein expression. Only the sequence from - 1550 bp to - 1409 bp demonstrated a difference in luciferase expression in the both cell lines. According to the results of the 5'-UTR truncated vectors, there was a repression region at the distal end of the 5'-UTR, an enhancer region might be present at the proximal end of the transcription start site.

CONCLUSIONS: Although the functional sequences of the HTR1A gene regulatory region were confirmed, the regulatory factors and functional components require further investigation.}, } @article {pmid30594151, year = {2018}, author = {Zhang, Y and Fang, J and Wu, X and Dong, L}, title = {Na+/K+ Balance and Transport Regulatory Mechanisms in Weedy and Cultivated Rice (Oryza sativa L.) Under Salt Stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {375}, doi = {10.1186/s12870-018-1586-9}, pmid = {30594151}, issn = {1471-2229}, support = {201303022//Special Fund for Agro-scientific Research in the Public Interest, People's Republic of China/ ; }, abstract = {BACKGROUND: Salinization is a primary abiotic stress constraining global plant growth and production. Weedy rice, though highly homologous to cultivated rice, is more salt tolerant during seed germination and seedling growth; we hypothesize that this is owing to ionic homeostasis and changes in the expression of genes encoding ion transport regulators.

RESULTS: The four different genotypes of weedy (JYGY-1 and JYFN-4) and cultivated (Nipponbare and 9311) rice have different salt-tolerance during seed germination and seedling vegetative growth under salt stress. In this study, Na+ and Ca2+content increased in weedy and cultivated rice genotypes under salt stress while K+ and Mg2+decreased; however, JYGY-1 had the lowest Na+/K+ ratio of assessed genotypes. Genes in the high-affinity K+ transporter (HKT) and tonoplast sodium-hydrogen exchanger (NHX) families, and salt overly sensitive 1 (OsSOS1) have more than 98% homology in amino acid sequences between weedy and cultivated rice genotypes. Under salt stress, the HKT family members were differentially expressed in the roots and shoots of four different genotypes. However, the NHX family transcripts were markedly up-regulated in all genotypes, but there are significant differences between different genotypes. OsSOS1 was significantly up-regulated in roots, especially in JYGY-1genotype.

CONCLUSIONS: The results showed that different genotypes had different germination and nutrient survival under salt stress, which was related to the difference of ion content and the difference of a series of ion transport gene expression. At the same time this study will provide new insight into the similarities and differences in ion homeostasis and gene regulatory mechanisms between weedy and cultivated rice under salt stress, which can aid in novel rice breeding and growth strategies.}, } @article {pmid30594150, year = {2018}, author = {Shah, S and Karunarathna, NL and Jung, C and Emrani, N}, title = {An APETALA1 ortholog affects plant architecture and seed yield component in oilseed rape (Brassica napus L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {380}, doi = {10.1186/s12870-018-1606-9}, pmid = {30594150}, issn = {1471-2229}, support = {JU205/19-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Increasing the productivity of rapeseed as one of the widely cultivated oil crops in the world is of upmost importance. As flowering time and plant architecture play a key role in the regulation of rapeseed yield, understanding the genetic mechanism underlying these traits can boost the rapeseed breeding. Meristem identity genes are known to have pleiotropic effects on plant architecture and seed yield in various crops. To understand the function of one of the meristem identity genes, APETALA1 (AP1) in rapeseed, we performed phenotypic analysis of TILLING mutants under greenhouse conditions. Three stop codon mutant families carrying a mutation in Bna.AP1.A02 paralog were analyzed for different plant architecture and seed yield-related traits.

RESULTS: It was evident that stop codon mutation in the K domain of Bna.AP1.A02 paralog caused significant changes in flower morphology as well as plant architecture related traits like plant height, branch height, and branch number. Furthermore, yield-related traits like seed yield per plant and number of seeds per plants were also significantly altered in the same mutant family. Apart from phenotypic changes, stop codon mutation in K domain of Bna.AP1.A02 paralog also altered the expression of putative downstream target genes like Bna.TFL1 and Bna.FUL in shoot apical meristem (SAM) of rapeseed. Mutant plants carrying stop codon mutations in the COOH domain of Bna.AP1.A02 paralog did not have a significant effect on plant architecture, yield-related traits or the expression of the downstream targets.

CONCLUSIONS: We found that Bna.AP1.A02 paralog has pleiotropic effect on plant architecture and yield-related traits in rapeseed. The allele we found in the current study with a beneficial effect on seed yield can be incorporated into rapeseed breeding pool to develop new varieties.}, } @article {pmid30594146, year = {2018}, author = {Witzel, C and Kierdorf, U and Frölich, K and Kierdorf, H}, title = {The pay-off of hypsodonty - timing and dynamics of crown growth and wear in molars of Soay sheep.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {207}, doi = {10.1186/s12862-018-1332-9}, pmid = {30594146}, issn = {1471-2148}, abstract = {BACKGROUND: Several lineages of herbivorous mammals have evolved hypsodont cheek teeth to increase the functional lifespan of their dentition. While the selective drivers of this trend and the developmental processes involved have been studied in greater detail, thus far no quantitative information is available on the relationship between additional investment into tooth growth and the resulting extension of the functional period of these teeth. To achieve this, we performed a detailed analysis of molar crown growth in known-age Soay sheep repeatedly injected with different fluorochromes.

RESULTS: Our study revealed that in sheep molars especially the formation of the crown base portion is prolonged in comparison with other herbivorous artiodactyl species. Our results demonstrate that growth of the crown base accounted for more than half of the total crown formation time (CFT) of the anterior lobes of the first (approx. 220 days of total CFT of 300 days), second (approx. 260 of 460 days) and third (approx. 300 of at least 520 days) molars, and that the formation of this crown portion occurred largely after the teeth had already reached functional occlusion. By combining data on wear-related changes in crown morphology from the literature with the reconstructed additional investment into the crown base portion, it was possible to relate this additional investment to a prolongation of the functional periods of the molars ranging from 4 years in the M1 to 6 years in the M3.

CONCLUSIONS: Our results allow to establish a quantitative link between an additional investment into molar crown growth of sheep and the extension of the functional period of these teeth. The reported findings enable an assessment of the adaptive value, in terms of increased longevity, of an additional investment into crown elongation in a mammalian herbivore.}, } @article {pmid30594145, year = {2018}, author = {Schmidt, M and Hamacher, K}, title = {hoDCA: higher order direct-coupling analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {546}, doi = {10.1186/s12859-018-2583-6}, pmid = {30594145}, issn = {1471-2105}, mesh = {Humans ; Proteins/*metabolism ; Sequence Analysis, Protein/*methods ; }, abstract = {BACKGROUND: Direct-coupling analysis (DCA) is a method for protein contact prediction from sequence information alone. Its underlying principle is parameter estimation for a Hamiltonian interaction function stemming from a maximum entropy model with one- and two-point interactions. Vastly growing sequence databases enable the construction of large multiple sequence alignments (MSA). Thus, enough data exists to include higher order terms, such as three-body correlations.

RESULTS: We present an implementation of hoDCA, which is an extension of DCA by including three-body interactions into the inverse Ising problem posed by parameter estimation. In a previous study, these three-body-interactions improved contact prediction accuracy for the PSICOV benchmark dataset. Our implementation can be executed in parallel, which results in fast runtimes and makes it suitable for large-scale application.

CONCLUSION: Our hoDCA software allows improved contact prediction using the Julia language, leveraging power of multi-core machines in an automated fashion.}, } @article {pmid30594144, year = {2018}, author = {Wei, S and Wang, X and Jiang, D and Dong, S}, title = {Physiological and proteome studies of maize (Zea mays L.) in response to leaf removal under high plant density.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {378}, doi = {10.1186/s12870-018-1607-8}, pmid = {30594144}, issn = {1471-2229}, support = {BK20170720//the Natural Science Foundation of Jiangsu Province/ ; 2017M611832//the China Postdoctoral Science Foundation funded project/ ; 1701040A//the Postdoctoral Science Foundation funded project of Jiangsu Province/ ; 2016YFD0300308//the national key research and development program of China/ ; 31171497//the National Natural Science Foundation of China/ ; 2011CB100105//the National Basic Research Program of China/ ; 2011BAD16B09//the National Food Science and Technology of High-yield Program of China/ ; 20120306//the Special Fund for Agro-scientific Research in the Public Interest of China/ ; B16026//111 Project/ ; }, abstract = {BACKGROUND: Under high plant density, intensifying competition among individual plants led to overconsumption of energy and nutrients and resulted in an almost dark condition in the lower strata of the canopy, which suppressed the photosynthetic potential of the shaded leaves. Leaf removal could help to ameliorate this problem and increase crop yields. To reveal the mechanism of leaf removal in maize, tandem mass tags label-based quantitative analysis coupled with liquid chromatography-tandem mass spectrometry were used to capture the differential protein expression profiles of maize subjected to the removal of the two uppermost leaves (S2), the four uppermost leaves (S4), and with no leaf removal as control (S0).

RESULTS: Excising leaves strengthened the light transmission rate of the canopy and increased the content of malondialdehyde, whereas decreased the activities of superoxide dismutase and peroxidase. Two leaves removal increased the photosynthetic capacity of ear leaves and the grain yield significantly, whereas S4 decreased the yield markedly. Besides, 239 up-accumulated proteins and 99 down-accumulated proteins were identified between S2 and S0, which were strongly enriched into 30 and 23 functional groups; 71 increased proteins and 42 decreased proteins were identified between S4 and S0, which were strongly enriched into 22 and 23 functional groups, for increased and decreased proteins, respectively.

CONCLUSIONS: Different defoliation levels had contrastive effects on maize. The canopy light transmission rate was strengthened and proteins related to photosynthetic electron-transfer reaction were up-regulated significantly for treatment S2, which improved the leaf photosynthetic capacity, and obtained a higher grain yield consequently. In contrast, S4 decreased the grain yield and increased the expressions of proteins and genes associated with fatty acid metabolism. Besides, both S2 and S4 exaggerated the defensive response of maize in physiological and proteomic level. Although further studies are required, the results in our study provide new insights to the further improvement in maize grain yield by leaf removal.}, } @article {pmid30594143, year = {2018}, author = {Ignasiak, K and Maxwell, A}, title = {Oxytetracycline reduces the diversity of tetracycline-resistance genes in the Galleria mellonella gut microbiome.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {228}, doi = {10.1186/s12866-018-1377-3}, pmid = {30594143}, issn = {1471-2180}, support = {BB/J004656/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Clinically-relevant multidrug resistance is sometimes present in bacteria not exposed to human-made antibiotics, in environments without extreme selective pressures, such as the insect gut. The use of antibiotics on naïve microbiomes often leads to decreased microbe diversity and increased antibiotic resistance.

RESULTS: Here we investigate the impact of antibiotics on the insect gut microbiome by identifying tetracycline-resistance genes in the gut bacteria of greater wax moth (Galleria mellonella) larvae, feeding on artificial food containing oxytetracycline. We determined that G. mellonella can be raised on artificial food for over five generations and that the insects tolerate low doses of antibiotics in their diets, but doses of oxytetracycline higher than sub-inhibitory lead to early larval mortality. In our experiments, greater wax moth larvae had a sparse microbiome, which is consistent with previous findings. Additionally, we determined that the microbiome of G. mellonella larvae not exposed to antibiotics carries a number of tetracycline-resistance genes and some of that diversity is lost upon exposure to strong selective pressure.

CONCLUSIONS: We show that G. mellonella larvae can be raised on artificial food, including antibiotics, for several generations and that the microbiome can be sampled. We show that, in the absence of antibiotics, the insect gut microbiome can maintain a diverse pool of tetracycline-resistance genes. Selective pressure, from exposure to the antibiotic oxytetracycline, leads to microbiome changes and alteration in the tetracycline-resistance gene pool.}, } @article {pmid30594141, year = {2018}, author = {Mehner, T and Pohlmann, K and Bittner, D and Freyhof, J}, title = {Testing the devil's impact on southern Baltic and North Sea basins whitefish (Coregonus spp.) diversity.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {208}, doi = {10.1186/s12862-018-1339-2}, pmid = {30594141}, issn = {1471-2148}, abstract = {BACKGROUND: The diversity and phylogeny of whitefish of the genus Coregonus is complex, and includes many endemic species of high conservation concern. However, because of commercial importance of whitefish fisheries, stockings and translocations have occurred repeatedly, which challenges the identification of local populations as conservation units. This study analyses the phylogenetic relationships of 15 contemporary and two historical populations of lake-resident and anadromous whitefish (Coregonus spp.) from the southern Baltic and North Sea basins. We elucidated the complex history of Lake Schaal (northern Germany) whitefish, for which a local tale suggests that the devil threw whitefish from the Central European Lake Constance into this lake. Studies from the early twentieth century indeed suggested numerous stocking events for Lake Schaal from Lake Constance, from Estonian/Russian Lake Peipsi and from the anadromous whitefish of the Baltic Sea.

RESULTS: Analyses of 13 microsatellite markers showed that Lake Constance whitefish are unrelated to any northern Germany whitefish population, including the contemporary whitefish population from Lake Schaal. Comparison with four historical specimens further showed that the native Lake Schaal whitefish (C. holsatus) vanished from the lake, but has survived as a non-native population in the north German Lake Drewitz. The whitefish currently occurring in Lake Schaal and three adjacent lakes are identified as C. maraenoides, introduced from Lake Peipsi. The contemporary anadromous whitefish populations from the Baltic (German and Finnish coast) and the German River Treene (North Sea basin, stocked from Danish River Vida) grouped together, but showed significant genetic differentiation. The 14 historical specimens of C. oxyrinchus from Rivers Rhine and Schelde were assigned to several contemporary whitefish populations, but among them only one specimen was assigned to the contemporary River Treene population. Therefore, we do not support the view that the whitefish from River Vida/Treene are identical with the historical C. oxyrinchus.

CONCLUSIONS: Our study demonstrates that lake and anadromous whitefish in the Baltic and North Sea basins reflect a complex phylogeography, which is further blurred by the effects of repeated stocking and translocations. To identify conservation units, the genetic identity of each population has to be scrutinized.}, } @article {pmid30594137, year = {2018}, author = {Eyer, PA and McDowell, B and Johnson, LNL and Calcaterra, LA and Fernandez, MB and Shoemaker, D and Puckett, RT and Vargo, EL}, title = {Supercolonial structure of invasive populations of the tawny crazy ant Nylanderia fulva in the US.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {209}, doi = {10.1186/s12862-018-1336-5}, pmid = {30594137}, issn = {1471-2148}, abstract = {BACKGROUND: Social insects are among the most serious invasive pests in the world, particularly successful at monopolizing environmental resources to outcompete native species and achieve ecological dominance. The invasive success of some social insects is enhanced by their unicolonial structure, under which the presence of numerous queens and the lack of aggression against non-nestmates allow high worker densities, colony growth, and survival while eliminating intra-specific competition. In this study, we investigated the population genetics, colony structure and levels of aggression in the tawny crazy ant, Nylanderia fulva, which was recently introduced into the United States from South America.

RESULTS: We found that this species experienced a genetic bottleneck during its invasion lowering its genetic diversity by 60%. Our results show that the introduction of N. fulva is associated with a shift in colony structure. This species exhibits a multicolonial organization in its native range, with colonies clearly separated from one another, whereas it displays a unicolonial system with no clear boundaries among nests in its invasive range. We uncovered an absence of genetic differentiation among populations across the entire invasive range, and a lack of aggressive behaviors towards conspecifics from different nests, even ones separated by several hundreds of kilometers.

CONCLUSIONS: Overall, these results suggest that across its entire invasive range in the U.S.A., this species forms a single supercolony spreading more than 2000 km. In each invasive nest, we found several, up to hundreds, of reproductive queens, each being mated with a single male. The many reproductive queens per nests, together with the free movement of individuals between nests, leads to a relatedness coefficient among nestmate workers close to zero in introduced populations, calling into question the stability of this unicolonial system in which indirect fitness benefits to workers is apparently absent.}, } @article {pmid30594136, year = {2018}, author = {Yuan, Y and Yu, M and Jia, Z and Song, X and Liang, Y and Zhang, J}, title = {Analysis of Dendrobium huoshanense transcriptome unveils putative genes associated with active ingredients synthesis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {978}, doi = {10.1186/s12864-018-5305-6}, pmid = {30594136}, issn = {1471-2164}, support = {Grant No. 201504406//National Special Fund for Forestry Scientific Research in the Public Interest/ ; PAPD//the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; Grant No. CX (17)1004//Jiangsu Agriculture Science and Technology Innovation Fund/ ; ZYYS-2014 [12]//the National traditional Chinese medicine standardization project/ ; }, abstract = {BACKGROUND: Dendrobium huoshanense C.Z. Tang et S.J. Cheng is a traditional Chinese herbal medicine with high medicinal value in China. Polysaccharides and alkaloids are its main active ingredients. To understand the difference of main active ingredients in different tissues, we determined the contents of polysaccharides and alkaloids in the roots, stems and leaves of D. huoshanense. In order to explore the reasons for the differences of active ingredients at the level of transcription, we selected roots, stems and leaves of D. huoshanenese for transcriptome sequencing and pathway mining.

RESULTS: The contents of polysaccharides and alkaloids of D. huoshanense were determined and it was found that there were significant differences in different tissues. A total of 716,634,006 clean reads were obtained and 478,361 unigenes were assembled by the Illumina platform sequencing. We identified 1407 carbohydrate-active related unigenes against CAZy database including 447 glycosyltransferase genes (GTs), 818 glycoside hydrolases (GHs), 60 carbohydrate esterases (CEs), 62 carbohydrate-binding modules (CBMs), and 20 polysaccharide lyases (PLs). In the glycosyltransferases (GTs) family, 315 differential expression genes (DEGs) were identified. In total, 124 and 58 DEGs were associated with the biosynthesis of alkaloids in Dh_L vs. Dh_S and Dh_R vs. Dh_L, respectively. A total of 62 DEGs associated with the terpenoid pathway were identified between Dh_R and Dh_S. Five key enzyme genes involved in the terpenoids pathway were identified, and their expression patterns in different tissues was validated using quantitative real-time PCR.

CONCLUSIONS: In summary, our study presents a transcriptome profile of D. huoshanense. These data contribute to our deeper relevant researches on active ingredients and provide useful insights into the molecular mechanisms regulating polysaccharides and alkaloids in Dendrobium.}, } @article {pmid30594134, year = {2018}, author = {Bahari, MNA and Sakeh, NM and Abdullah, SNA and Ramli, RR and Kadkhodaei, S}, title = {Transciptome profiling at early infection of Elaeis guineensis by Ganoderma boninense provides novel insights on fungal transition from biotrophic to necrotrophic phase.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {377}, doi = {10.1186/s12870-018-1594-9}, pmid = {30594134}, issn = {1471-2229}, support = {5526302//NanoMalaysia Institute for Innovative Technology (NanoMITe) Consortium/ ; }, abstract = {BACKGROUND: Basal stem rot (BSR) caused by hemibiotroph Ganoderma boninense is a devastating disease resulting in a major loss to the oil palm industry. Since there is no physical symptom in oil palm at the early stage of G. boninense infection, characterisation of molecular defense responses in oil palm during early interaction with the fungus is of the utmost importance. Oil palm (Elaeis guineensis) seedlings were artificially infected with G. boninense inoculums and root samples were obtained following a time-course of 0, 3, 7, and 11 days-post-inoculation (d.p.i) for RNA sequencing (RNA-seq) and identification of differentially expressed genes (DEGs).

RESULTS: The host counter-attack was evidenced based on fungal hyphae and Ganoderma DNA observed at 3 d.p.i which became significantly reduced at 7 and 11 d.p.i. DEGs revealed upregulation of multifaceted defense related genes such as PR-protein (EgPR-1), protease inhibitor (EgBGIA), PRR protein (EgLYK3) chitinase (EgCht) and expansin (EgEXPB18) at 3 d.p.i and 7 d.p.i which dropped at 11 d.p.i. Later stage involved highly expressed transcription factors EgERF113 and EgMYC2 as potential regulators of necrotrophic defense at 11 d.p.i. The reactive oxygen species (ROS) elicitor: peroxidase (EgPER) and NADPH oxidase (EgRBOH) were upregulated and maintained throughout the treatment period. Growth and nutrient distribution were probably compromised through suppression of auxin signalling and iron uptake genes.

CONCLUSIONS: Based on the analysis of oil palm gene expression, it was deduced that the biotrophic phase of Ganoderma had possibly occurred at the early phase (3 until 7 d.p.i) before being challenged by the fungus via switching its lifestyle into the necrotrophic phase at later stage (11 d.p.i) and finally succumbed the host. Together, the findings suggest the dynamic defense process in oil palm and potential candidates that can serve as phase-specific biomarkers at the early stages of oil palm-G. boninense interaction.}, } @article {pmid30594132, year = {2018}, author = {Pucker, B and Brockington, SF}, title = {Genome-wide analyses supported by RNA-Seq reveal non-canonical splice sites in plant genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {980}, doi = {10.1186/s12864-018-5360-z}, pmid = {30594132}, issn = {1471-2164}, abstract = {BACKGROUND: Most eukaryotic genes comprise exons and introns thus requiring the precise removal of introns from pre-mRNAs to enable protein biosynthesis. U2 and U12 spliceosomes catalyze this step by recognizing motifs on the transcript in order to remove the introns. A process which is dependent on precise definition of exon-intron borders by splice sites, which are consequently highly conserved across species. Only very few combinations of terminal dinucleotides are frequently observed at intron ends, dominated by the canonical GT-AG splice sites on the DNA level.

RESULTS: Here we investigate the occurrence of diverse combinations of dinucleotides at predicted splice sites. Analyzing 121 plant genome sequences based on their annotation revealed strong splice site conservation across species, annotation errors, and true biological divergence from canonical splice sites. The frequency of non-canonical splice sites clearly correlates with their divergence from canonical ones indicating either an accumulation of probably neutral mutations, or evolution towards canonical splice sites. Strong conservation across multiple species and non-random accumulation of substitutions in splice sites indicate a functional relevance of non-canonical splice sites. The average composition of splice sites across all investigated species is 98.7% for GT-AG, 1.2% for GC-AG, 0.06% for AT-AC, and 0.09% for minor non-canonical splice sites. RNA-Seq data sets of 35 species were incorporated to validate non-canonical splice site predictions through gaps in sequencing reads alignments and to demonstrate the expression of affected genes.

CONCLUSION: We conclude that bona fide non-canonical splice sites are present and appear to be functionally relevant in most plant genomes, although at low abundance.}, } @article {pmid30594131, year = {2018}, author = {Guo, ZL and Li, JZ and Ma, YY and Qian, D and Zhong, JY and Jin, MM and Huang, P and Che, LY and Pan, B and Wang, Y and Sun, ZX and Liu, CZ}, title = {Shikonin sensitizes A549 cells to TRAIL-induced apoptosis through the JNK, STAT3 and AKT pathways.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {29}, doi = {10.1186/s12860-018-0179-7}, pmid = {30594131}, issn = {1471-2121}, support = {zz2018006//Research Project of CACMS/ ; 31170829//National Natural Science Foundation of China/ ; 81171762//National Natural Science Foundation of China/ ; 81550017//National Natural Science Foundation of China/ ; 81473418//National Natural Science Foundation of China/ ; 7172150//Beijing Municipal Natural Science Foundation/ ; }, abstract = {BACKGROUND: TRAIL, tumor necrosis factor-related apoptosis-inducing ligand, can selectively kill cancer cells with little or no cytotoxicity toward normal human cells and is regarded as a potential relatively safe antitumor drug. However, some cancer cells are resistant to TRAIL-induced apoptosis. Thus, reagents that potentiate TRAIL-induced cytotoxicity are needed. Herein, we investigated whether shikonin, a natural compound from the root of Lithospermum erythrorhizon, can sensitize TRAIL-resistant cells to TRAIL-induced cytotoxicity.

RESULTS: The viability of A549 cells, which were resistant to TRAIL, was significantly decreased after treatment with TRAIL followed by shikonin. The underlying mechanisms by which shikonin sensitizes cells to TRAIL-induced cytotoxicity were also examined. Combined treatment with shikonin and TRAIL activated the caspase and JNK pathways, inhibited the STAT3 and AKT pathways, downregulated the expression of Mcl-1, Bcl-2, Bcl-xL, c-FLIP and XIAP and upregulated the expression of Bid.

CONCLUSIONS: In conclusion, the results indicated that shikonin sensitized resistant cancer cells to TRAIL-induced cytotoxicity via the modulation of the JNK, STAT3 and AKT pathways, the downregulation of antiapoptotic proteins and the upregulation of proapoptotic proteins.}, } @article {pmid30594130, year = {2018}, author = {Rodrigues, AS and De Vega, JJ and Miguel, CM}, title = {Comprehensive assembly and analysis of the transcriptome of maritime pine developing embryos.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {379}, doi = {10.1186/s12870-018-1564-2}, pmid = {30594130}, issn = {1471-2229}, support = {289841-PROCOGEN//European Commission (FP7)/ ; IF/01168/2013//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/79779/2011//Fundação para a Ciência e a Tecnologia/ ; GREEN-it (UID/Multi/04551/2013)//Fundação para a Ciência e a Tecnologia/ ; BBS/E/T/000PR9818//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: There are clear differences in embryo development between angiosperm and gymnosperm species. Most of the current knowledge on gene expression and regulation during plant embryo development has derived from studies on angiosperms species, in particular from the model plant Arabidopsis thaliana. The few published studies on transcript profiling of conifer embryogenesis show the existence of many putative embryo-specific transcripts without an assigned function. In order to extend the knowledge on the transcriptomic expression during conifer embryogenesis, we sequenced the transcriptome of zygotic embryos for several developmental stages that cover most of Pinus pinaster (maritime pine) embryogenesis.

RESULTS: Total RNA samples collected from five zygotic embryo developmental stages were sequenced with Illumina technology. A de novo transcriptome was assembled as no genome sequence is yet published for Pinus pinaster. The transcriptome of reference for the period of zygotic embryogenesis in maritime pine contains 67,429 transcripts, which likely encode 58,527 proteins. The annotation shows a significant percentage, 31%, of predicted proteins exclusively present in pine embryogenesis. Functional categories and enrichment analysis of the differentially expressed transcripts evidenced carbohydrate transport and metabolism over-representation in early embryo stages, as highlighted by the identification of many putative glycoside hydrolases, possibly associated with cell wall modification, and carbohydrate transport transcripts. Moreover, the predominance of chromatin remodelling events was detected in early to middle embryogenesis, associated with an active synthesis of histones and their post-translational modifiers related to increased transcription, as well as silencing of transposons.

CONCLUSIONS: Our results extend the understanding of gene expression and regulation during zygotic embryogenesis in conifers and are a valuable resource to support further improvements in somatic embryogenesis for vegetative propagation of conifer species. Specific transcripts associated with carbohydrate metabolism, monosaccharide transport and epigenetic regulation seem to play an important role in pine early embryogenesis and may be a source of reliable molecular markers for early embryogenesis.}, } @article {pmid30594129, year = {2018}, author = {Wang, W and Schalamun, M and Morales-Suarez, A and Kainer, D and Schwessinger, B and Lanfear, R}, title = {Assembly of chloroplast genomes with long- and short-read data: a comparison of approaches using Eucalyptus pauciflora as a test case.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {977}, doi = {10.1186/s12864-018-5348-8}, pmid = {30594129}, issn = {1471-2164}, support = {FT140100843//Australian Research Council Future Fellowship/ ; }, abstract = {BACKGROUND: Chloroplasts are organelles that conduct photosynthesis in plant and algal cells. The information chloroplast genome contained is widely used in agriculture and studies of evolution and ecology. Correctly assembling chloroplast genomes can be challenging because the chloroplast genome contains a pair of long inverted repeats (10-30 kb). Typically, it is simply assumed that the gross structure of the chloroplast genome matches the most commonly observed structure of two single-copy regions separated by a pair of inverted repeats. The advent of long-read sequencing technologies should remove the need to make this assumption by providing sufficient information to completely span the inverted repeat regions. Yet, long-reads tend to have higher error rates than short-reads, and relatively little is known about the best way to combine long- and short-reads to obtain the most accurate chloroplast genome assemblies. Using Eucalyptus pauciflora, the snow gum, as a test case, we evaluated the effect of multiple parameters, such as different coverage of long-(Oxford nanopore) and short-(Illumina) reads, different long-read lengths, different assembly pipelines, with a view to determining the most accurate and efficient approach to chloroplast genome assembly.

RESULTS: Hybrid assemblies combining at least 20x coverage of both long-reads and short-reads generated a single contig spanning the entire chloroplast genome with few or no detectable errors. Short-read-only assemblies generated three contigs (the long single copy, short single copy and inverted repeat regions) of the chloroplast genome. These contigs contained few single-base errors but tended to exclude several bases at the beginning or end of each contig. Long-read-only assemblies tended to create multiple contigs with a much higher single-base error rate. The chloroplast genome of Eucalyptus pauciflora is 159,942 bp, contains 131 genes of known function.

CONCLUSIONS: Our results suggest that very accurate assemblies of chloroplast genomes can be achieved using a combination of at least 20x coverage of long- and short-reads respectively, provided that the long-reads contain at least ~5x coverage of reads longer than the inverted repeat region. We show that further increases in coverage give little or no improvement in accuracy, and that hybrid assemblies are more accurate than long-read-only or short-read-only assemblies.}, } @article {pmid30594128, year = {2018}, author = {Shi, X and Waiho, K and Li, X and Ikhwanuddin, M and Miao, G and Lin, F and Zhang, Y and Li, S and Zheng, H and Liu, W and Aweya, JJ and Azmie, G and Baylon, JC and Quinitio, ET and Ma, H}, title = {Female-specific SNP markers provide insights into a WZ/ZZ sex determination system for mud crabs Scylla paramamosain, S. tranquebarica and S. serrata with a rapid method for genetic sex identification.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {981}, doi = {10.1186/s12864-018-5380-8}, pmid = {30594128}, issn = {1471-2164}, support = {2018YFD0900201//the National Key Research & Development Program of China/ ; 31772837//the National Natural Science Foundation of China/ ; 2016-44//the Science and Technology Project of Shantou City/ ; NTF17006//the STU Scientific Research Foundation for Talents/ ; 2017KCXTD014//the Programme for Innovation and Enhancement of School of Department of Education of Guangdong Province/ ; Yueyu2018-11//the Program of Ocean and Fishery Department of Guangdong Province/ ; }, abstract = {BACKGROUND: Mud crabs, Scylla spp., are commercially important large-size marine crustaceans in the Indo-West Pacific region. As females have the higher growth rate and economic value, the production of all female stocks is extremely essential in aquaculture. However, the sex determination mechanism is still unclear. Development of sex-specific genetic markers based on next-generation sequencing proved to be an effective tool for discovering sex determination system in various animals.

RESULTS: Restriction-site associated DNA sequencing (RAD-seq) was employed to isolate sex-specific SNP markers for S. paramamosain. A total of 335.6 million raw reads were obtained from 20 individuals, of which 204.7 million were from 10 females and 130.9 million from 10 males. After sequence assembly and female-male comparison, 20 SNP markers were identified to be sex-specific. Furthermore, ten SNPs in a short sequence (285 bp) were confirmed heterozygous in females and homozygous in males in a large population by PCR amplification and sequencing. Subsequently, a female-specific primer was successfully designed according to the female-specific nucleotide which could amplify an expected band from females but not from males. Thus, a rapid and effective method for molecular sexing in S. paramamosain was developed, meanwhile, this method could successfully identify the sex of S. tranquebarica and S. serrata. Finally, nine and four female-specific SNP markers were detected in S. tranquebarica and S. serrata, respectively.

CONCLUSIONS: Sex-specific SNP markers were firstly identified in crab species and showed female heterogamety and male homogamety, which provided strong genetic evidence for a WZ/ZZ sex determination system in mud crabs S. paramamosain, S. tranquebarica and S. serrata. These findings will lay a solid foundation for the study of sex determination mechanism, sex chromosome evolution, and the development of mono-sex population in crustaceans.}, } @article {pmid30594127, year = {2018}, author = {Chen, L and Barnett, RE and Horstmann, M and Bamberger, V and Heberle, L and Krebs, N and Colbourne, JK and Gómez, R and Weiss, LC}, title = {Mitotic activity patterns and cytoskeletal changes throughout the progression of diapause developmental program in Daphnia.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {30}, doi = {10.1186/s12860-018-0181-0}, pmid = {30594127}, issn = {1471-2121}, support = {GSC 98/3//Deutsche Forschungsgemeinschaft/ ; Midlands Integrative Biosciences Training Partnership//Biotechnology and Biological Sciences Research Council (GB)/ ; }, abstract = {BACKGROUND: Diapause is a form of dormancy that is genetically predetermined to allow animals to overcome harsh environmental conditions. It is induced by predictive environmental cues bringing cellular activity levels into a state of suspended animation. Entering diapause requires organismal, molecular and cellular adaptation to severely reduced energy flows. Cells must therefore have evolved strategies that prepare them for periods with limited metabolic resources. However, changes that occur on the (sub-)cellular level have not been thoroughly described.

RESULTS: We investigated mitotic activity and we monitored cytoskeletal network changes in successive stages of diapausing and non-diapausing Daphnia magna embryos using (immuno-)fluorescent labeling. We find that embryos destined to diapause show a delayed and 2.5x slower mitotic activity in comparison to continuously developing embryos. Development is halted when D. magna embryos reach ~ 3500 cells, whereupon mitotic activity is absent and cytoskeletal components are severely reduced, rendering diapause cells compact and condensed.

CONCLUSION: In the initiation phase of diapause, the slower cell division rate points to prolonged interphase duration, preparing the cells for diapause maintenance. During diapause, cytoskeletal depletion and cellular condensation may be a means to save energy resources. Our data provide insights into the sub-cellular change of diapause in Daphnia.}, } @article {pmid30594125, year = {2018}, author = {Loarce, Y and Dongil, P and Fominaya, A and González, JM and Ferrer, E}, title = {PK-profiling method for identifying the expression of resistance-associated genes in partially resistant oats to crown rust.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {376}, doi = {10.1186/s12870-018-1604-y}, pmid = {30594125}, issn = {1471-2229}, support = {AGL2010-17042//Ministerio de Economía y Competitividad/ ; UAHGC2014-002//Universidad de Alcalá (ES)/ ; }, abstract = {BACKGROUND: Protein kinases play a key role in plant cell homeostasis and the activation of defense mechanisms. Partial resistance to fungi in plants is interesting because of its durability. However, the variable number of minor loci associated with this type of resistance hampers the reliable identification of the full range of genes involved. The present work reports the technique of protein kinase (PK)-profiling for the identification of the PK genes induced in the partially resistant oats line MN841801-1 following exposure to the fungus Puccinia coronata. This is the first time this technique has been used with cDNA (complementary DNA) from a suppression subtractive hybridization library obtained after the hybridization of cDNAs from inoculated and mock-inoculated plants.

RESULTS: Six degenerate primers based on the conserved domains of protein kinases were used in a PK-profiling assay including cDNA from mock-inoculated leaves and subtracted cDNA. Of the 75.7% of sequences cloned and sequenced that showed significant similarity to resistance genes, 76% were found to code for PKs. Translation and ClustalW2 alignment of each sequence cloned with the complete sequences of the most similar B. distachyon PKs allowed those of the partially resistant oat line to be deduced and characterized. Further, a phylogenetic study carried out after alignment of these B. distachyon PK sequences with the most similar protein sequences of related species also allowed to deduce different functions for the PK cloned. RT-qPCR (Reverse Transcription-quantitative PCR) was analyzed on nine representative sequences to validate the reliability of the employed PK-profiling method as a tool for identifying the expression of resistance-associated genes.

CONCLUSIONS: PK-profiling would appear to be a useful tool for the identification of the PKs expressed in oats after challenge by P. coronata, and perhaps other pathogens. Most of the PKs studied are related to receptor-like protein kinases expressed shortly after infection. This is in agreement with previous studies indicating a close relationship between partial resistance and the first layer of defense against pathogen used by plants.}, } @article {pmid30594123, year = {2018}, author = {Girnyk, AE and Vergun, AA and Semyenova, SK and Guliaev, AS and Arakelyan, MS and Danielyan, FD and Martirosyan, IA and Murphy, RW and Ryskov, AP}, title = {Multiple interspecific hybridization and microsatellite mutations provide clonal diversity in the parthenogenetic rock lizard Darevskia armeniaca.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {979}, doi = {10.1186/s12864-018-5359-5}, pmid = {30594123}, issn = {1471-2164}, support = {17-00-00430 (17-00-00426)//Russian Foundation for Basic Research/ ; 17-04-00396//Russian Foundation for Basic Research/ ; Molecular and Cell Biology//Russian Academy of Sciences/ ; GK-02.451.11.7060//Russian Academy of Sciences/ ; }, abstract = {BACKGROUND: The parthenogenetic Caucasian rock lizard Darevskia armeniaca, like most other parthenogenetic vertebrate species, originated through interspecific hybridization between the closely related sexual Darevskia mixta and Darevskia valentini. Darevskia armeniaca was shown to consist of one widespread allozyme clone and a few rare ones, but notwithstanding the origin of clonal diversity remains unclear. We conduct genomic analysis of D. armeniaca and its parental sexual species using microsatellite and SNP markers to identify the origin of parthenogenetic clonal lineages.

RESULTS: Four microsatellite-containing loci were genotyped for 111 specimens of D. armeniaca, 17 D. valentini, and four D. mixta. For these species, a total of 47 alleles were isolated and sequenced. Analysis of the data revealed 13 genotypes or presumptive clones in parthenogenetic D. armeniaca, including one widespread clone, two apparently geographically restricted clones, and ten rare clones. Comparisons of genotype-specific markers in D. armeniaca with those of its parental species revealed three founder-events including a common and two rare clones. All other clones appeared to have originated via post-formation microsatellite mutations in the course of evolutionary history of D. armeniaca.

CONCLUSION: Our new approach to microsatellite genotyping reveals allele-specific microsatellite and SNP markers for each locus studied. Interspecies comparison of these markers identifies alleles inherited by parthenospecies from parental species, and provides new information on origin and evolution of clonal diversity in D. armeniaca. SNP analyses reveal at least three interspecific origins of D. armeniaca, and microsatellite mutations in these initial clones give rise to new clones. Thus, we first establish multiple origins of D. armeniaca. Our study identifies the most effective molecular markers for elucidating the origins of clonal diversity in other unisexual species that arose via interspecific hybridization.}, } @article {pmid30594121, year = {2018}, author = {Nguyen, P and Braun, R}, title = {Time-lagged Ordered Lasso for network inference.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {545}, doi = {10.1186/s12859-018-2558-7}, pmid = {30594121}, issn = {1471-2105}, support = {220020394//James S. McDonnell Foundation/ ; DMS-1547394//National Science Foundation/ ; }, mesh = {Gene Expression/*genetics ; Gene Regulatory Networks/*genetics ; Humans ; *Regression Analysis ; }, abstract = {BACKGROUND: Accurate gene regulatory networks can be used to explain the emergence of different phenotypes, disease mechanisms, and other biological functions. Many methods have been proposed to infer networks from gene expression data but have been hampered by problems such as low sample size, inaccurate constraints, and incomplete characterizations of regulatory dynamics. Since expression regulation is dynamic, time-course data can be used to infer causality, but these datasets tend to be short or sparsely sampled. In addition, temporal methods typically assume that the expression of a gene at a time point depends on the expression of other genes at only the immediately preceding time point, while other methods include additional time points without any constraints to account for their temporal distance. These limitations can contribute to inaccurate networks with many missing and anomalous links.

RESULTS: We adapted the time-lagged Ordered Lasso, a regularized regression method with temporal monotonicity constraints, for de novo reconstruction. We also developed a semi-supervised method that embeds prior network information into the Ordered Lasso to discover novel regulatory dependencies in existing pathways. R code is available at https://github.com/pn51/laggedOrderedLassoNetwork .

CONCLUSIONS: We evaluated these approaches on simulated data for a repressilator, time-course data from past DREAM challenges, and a HeLa cell cycle dataset to show that they can produce accurate networks subject to the dynamics and assumptions of the time-lagged Ordered Lasso regression.}, } @article {pmid30593664, year = {2018}, author = {Yuan, ML and Wake, MH and Wang, IJ}, title = {Phenotypic integration between claw and toepad traits promotes microhabitat specialization in the Anolis adaptive radiation.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13673}, pmid = {30593664}, issn = {1558-5646}, support = {//Smithsonian Institution Graduate Fellowship/ ; #1542534//National Science Foundation Dimensions of Biodiversity/ ; 1542534//Division of Environmental Biology/ ; //National Museum of Natural History/ ; }, abstract = {The performance of an organism in its environment frequently depends more on its composite phenotype than on individual phenotypic traits. Thus, understanding environmental adaptation requires investigating patterns of covariation across functionally related traits. The replicated adaptive radiations of Greater Antillean Anolis lizards are characterized by ecological and morphological convergence, thus, providing an opportunity to examine the role of multiple phenotypes in microhabitat adaptation. Here, we examine integrated claw and toepad morphological evolution in relation to habitat partitioning across the adaptive radiations of Greater Antillean anoles. Based on analysis of 428 specimens from 57 species, we found that different aspects of claw morphology were associated with different perch dimensions, with claw height positively associated with perch diameter and claw curvature positively associated with perch height. Patterns of integration also varied across claw and toepad traits, likely driven by correlative selection for performance on smoother and rougher substrates. Finally, rates of evolution differed between claw and toepad traits, with claw length evolving faster than all other traits despite having no predicted functional importance. Our results highlight the multivariate nature of phenotypic adaptation and suggest that phenotypic integration across Greater Antillean anoles is driven by fine-scale correlative selection based on structural habitat specialization.}, } @article {pmid30593663, year = {2018}, author = {Márquez, R and Ramírez-Castañeda, V and Amézquita, A}, title = {Does batrachotoxin autoresistance coevolve with toxicity in Phyllobates poison-dart frogs?.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13672}, pmid = {30593663}, issn = {1558-5646}, support = {Fellowship for Young Researchers//Departamento Administrativo de Ciencia, Tecnología e Innovación/ ; Innovators (O//Departamento Administrativo de Ciencia, Tecnología e Innovación/ ; Proyecto Semilla//Universidad de los Andes/ ; Proyecto de Ciencias Basicas//Universidad de los Andes/ ; 1702014//Division of Environmental Biology/ ; }, abstract = {Toxicity is widespread among living organisms, and evolves as a multimodal phenotype. Part of this phenotype is the ability to avoid self-intoxication (autoresistance). Evolving toxin resistance can involve fitness tradeoffs, so autoresistance is often expected to evolve gradually and in tandem with toxicity, resulting in a correlation between the degrees of toxicity and autoresistance among toxic populations. We investigate this correlation in Phyllobates poison frogs, notorious for secreting batrachotoxin (BTX), a potent neurotoxin that targets sodium channels, using ancestral sequence reconstructions of BTX-sensing areas of the muscular voltage-gated sodium channel. Reconstructions suggest that BTX resistance arose at the root of Phyllobates, coinciding with the evolution of BTX secretion. After this event, little or no further evolution of autoresistance seems to have occurred, despite large increases in toxicity throughout the history of these frogs. Our results, therefore, provide no evidence in favor of an evolutionary correlation between toxicity and autoresistance, which conflicts with previous work. Future research on the functional costs and benefits of mutations putatively involved in BTX resistance, as well as their prevalence in natural populations, should shed light on the evolutionary mechanisms driving the relationship between toxicity and autoresistance in Phyllobates frogs.}, } @article {pmid30593658, year = {2018}, author = {Du, TY and Tissandier, SC and Larsson, HCE}, title = {Integration and modularity of teleostean pectoral fin shape and its role in the diversification of acanthomorph fishes.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13669}, pmid = {30593658}, issn = {1558-5646}, support = {CGS-D//Natural Sciences and Engineering Research Council of Canada/ ; Visiting Scientist Scholarship//Field Museum/ ; }, abstract = {Phenotypic integration and modularity describe the strength and pattern of interdependencies between traits. Integration and modularity have been proposed to influence the trajectory of evolution, either acting as constraints or facilitators. Here, we examine trends in the integration and modularity of pectoral fin morphology in teleost fishes using geometric morphometrics. We compare the fin shapes of the highly diverse radiation of acanthomorph fishes to lower teleosts. Integration and modularity are measured using two-block partial least squares analysis and the covariance ratio coefficient between the radial bones and lepidotrichia of the pectoral fins. We show that the fins of acanthomorph fishes are more tightly integrated but also more morphologically diverse and faster evolving compared to nonacanthomorph fishes. The main pattern of shape covariation in nonacanthomorphs is concordant with the main trajectory of evolution between nonacanthomorphs and acanthomorphs. Our findings support a facilitating role for integration during the acanthomorph diversification. Potential functional consequences and developmental mechanisms of fin integration are discussed.}, } @article {pmid30593567, year = {2019}, author = {Liu, N and Song, J and Xie, Y and Wang, XL and Rong, B and Man, N and Zhang, MM and Zhang, Q and Gao, FF and Du, MR and Zhang, Y and Shen, J and Xu, CH and Hu, CL and Wu, JC and Liu, P and Zhang, YL and Xie, YY and Liu, P and Huang, JY and Huang, QH and Lan, F and Shen, S and Nimer, SD and Chen, Z and Chen, SJ and Roeder, RG and Wang, L and Sun, XJ}, title = {Different roles of E proteins in t(8;21) leukemia: E2-2 compromises the function of AETFC and negatively regulates leukemogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {890-899}, doi = {10.1073/pnas.1809327116}, pmid = {30593567}, issn = {1091-6490}, support = {R01 CA163086/CA/NCI NIH HHS/United States ; R01 CA166835/CA/NCI NIH HHS/United States ; R01 CA178765/CA/NCI NIH HHS/United States ; }, abstract = {The AML1-ETO fusion protein, generated by the t(8;21) chromosomal translocation, is causally involved in nearly 20% of acute myeloid leukemia (AML) cases. In leukemic cells, AML1-ETO resides in and functions through a stable protein complex, AML1-ETO-containing transcription factor complex (AETFC), that contains multiple transcription (co)factors. Among these AETFC components, HEB and E2A, two members of the ubiquitously expressed E proteins, directly interact with AML1-ETO, confer new DNA-binding capacity to AETFC, and are essential for leukemogenesis. However, the third E protein, E2-2, is specifically silenced in AML1-ETO-expressing leukemic cells, suggesting E2-2 as a negative factor of leukemogenesis. Indeed, ectopic expression of E2-2 selectively inhibits the growth of AML1-ETO-expressing leukemic cells, and this inhibition requires the bHLH DNA-binding domain. RNA-seq and ChIP-seq analyses reveal that, despite some overlap, the three E proteins differentially regulate many target genes. In particular, studies show that E2-2 both redistributes AETFC to, and activates, some genes associated with dendritic cell differentiation and represses MYC target genes. In AML patients, the expression of E2-2 is relatively lower in the t(8;21) subtype, and an E2-2 target gene, THPO, is identified as a potential predictor of relapse. In a mouse model of human t(8;21) leukemia, E2-2 suppression accelerates leukemogenesis. Taken together, these results reveal that, in contrast to HEB and E2A, which facilitate AML1-ETO-mediated leukemogenesis, E2-2 compromises the function of AETFC and negatively regulates leukemogenesis. The three E proteins thus define a heterogeneity of AETFC, which improves our understanding of the precise mechanism of leukemogenesis and assists development of diagnostic/therapeutic strategies.}, } @article {pmid30593566, year = {2019}, author = {Cordeiro, S and Finol-Urdaneta, RK and Köpfer, D and Markushina, A and Song, J and French, RJ and Kopec, W and de Groot, BL and Giacobassi, MJ and Leavitt, LS and Raghuraman, S and Teichert, RW and Olivera, BM and Terlau, H}, title = {Conotoxin κM-RIIIJ, a tool targeting asymmetric heteromeric Kv1 channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {1059-1064}, doi = {10.1073/pnas.1813161116}, pmid = {30593566}, issn = {1091-6490}, support = {P01 GM048677/GM/NIGMS NIH HHS/United States ; }, abstract = {The vast complexity of native heteromeric K+ channels is largely unexplored. Defining the composition and subunit arrangement of individual subunits in native heteromeric K+ channels and establishing their physiological roles is experimentally challenging. Here we systematically explored this "zone of ignorance" in molecular neuroscience. Venom components, such as peptide toxins, appear to have evolved to modulate physiologically relevant targets by discriminating among closely related native ion channel complexes. We provide proof-of-principle for this assertion by demonstrating that κM-conotoxin RIIIJ (κM-RIIIJ) from Conus radiatus precisely targets "asymmetric" Kv channels composed of three Kv1.2 subunits and one Kv1.1 or Kv1.6 subunit with 100-fold higher apparent affinity compared with homomeric Kv1.2 channels. Our study shows that dorsal root ganglion (DRG) neurons contain at least two major functional Kv1.2 channel complexes: a heteromer, for which κM-RIIIJ has high affinity, and a putative Kv1.2 homomer, toward which κM-RIIIJ is less potent. This conclusion was reached by (i) covalent linkage of members of the mammalian Shaker-related Kv1 family to Kv1.2 and systematic assessment of the potency of κM-RIIIJ block of heteromeric K+ channel-mediated currents in heterologous expression systems; (ii) molecular dynamics simulations of asymmetric Kv1 channels providing insights into the molecular basis of κM-RIIIJ selectivity and potency toward its targets; and (iii) evaluation of calcium responses of a defined population of DRG neurons to κM-RIIIJ. Our study demonstrates that bioactive molecules present in venoms provide essential pharmacological tools that systematically target specific heteromeric Kv channel complexes that operate in native tissues.}, } @article {pmid30593565, year = {2019}, author = {Vallespir Lowery, N and Ursell, T}, title = {Structured environments fundamentally alter dynamics and stability of ecological communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {379-388}, doi = {10.1073/pnas.1811887116}, pmid = {30593565}, issn = {1091-6490}, abstract = {The dynamics and stability of ecological communities are intimately linked with the specific interactions-like cooperation or predation-between constituent species. In microbial communities, like those found in soils or the mammalian gut, physical anisotropies produced by fluid flow and chemical gradients impact community structure and ecological dynamics, even in structurally isotropic environments. Although natural communities existing in physically unstructured environments are rare, the role of environmental structure in determining community dynamics and stability remains poorly studied. To address this gap, we used modified Lotka-Volterra simulations of competitive microbial communities to characterize the effects of surface structure on community dynamics. We find that environmental structure has profound effects on communities, in a manner dependent on the specific pattern of interactions between community members. For two mutually competing species, eventual extinction of one competitor is effectively guaranteed in isotropic environments. However, addition of environmental structure enables long-term coexistence of both species via local "pinning" of competition interfaces, even when one species has a significant competitive advantage. In contrast, while three species competing in an intransitive loop (as in a game of rock-paper-scissors) coexist stably in isotropic environments, structural anisotropy disrupts the spatial patterns on which coexistence depends, causing chaotic population fluctuations and subsequent extinction cascades. These results indicate that the stability of microbial communities strongly depends on the structural environment in which they reside. Therefore, a more complete ecological understanding, including effective manipulation and interventions in natural communities of interest, must account for the physical structure of the environment.}, } @article {pmid30593564, year = {2019}, author = {Dym, N and Slutsky, R and Lipman, Y}, title = {Linear variational principle for Riemann mappings and discrete conformality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {732-737}, doi = {10.1073/pnas.1809731116}, pmid = {30593564}, issn = {1091-6490}, abstract = {We consider Riemann mappings from bounded Lipschitz domains in the plane to a triangle. We show that in this case the Riemann mapping has a linear variational principle: It is the minimizer of the Dirichlet energy over an appropriate affine space. By discretizing the variational principle in a natural way we obtain discrete conformal maps which can be computed by solving a sparse linear system. We show that these discrete conformal maps converge to the Riemann mapping in [Formula: see text], even for non-Delaunay triangulations. Additionally, for Delaunay triangulations the discrete conformal maps converge uniformly and are known to be bijective. As a consequence we show that the Riemann mapping between two bounded Lipschitz domains can be uniformly approximated by composing the discrete Riemann mappings between each Lipschitz domain and the triangle.}, } @article {pmid30593563, year = {2019}, author = {Serpas, L and Chan, RWY and Jiang, P and Ni, M and Sun, K and Rashidfarrokhi, A and Soni, C and Sisirak, V and Lee, WS and Cheng, SH and Peng, W and Chan, KCA and Chiu, RWK and Reizis, B and Lo, YMD}, title = {Dnase1l3 deletion causes aberrations in length and end-motif frequencies in plasma DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {641-649}, doi = {10.1073/pnas.1815031116}, pmid = {30593563}, issn = {1091-6490}, support = {R01 AR071703/AR/NIAMS NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; }, abstract = {Circulating DNA in plasma consists of short DNA fragments. The biological processes generating such fragments are not well understood. DNASE1L3 is a secreted DNASE1-like nuclease capable of digesting DNA in chromatin, and its absence causes anti-DNA responses and autoimmunity in humans and mice. We found that the deletion of Dnase1l3 in mice resulted in aberrations in the fragmentation of plasma DNA. Such aberrations included an increase in short DNA molecules below 120 bp, which was positively correlated with anti-DNA antibody levels. We also observed an increase in long, multinucleosomal DNA molecules and decreased frequencies of the most common end motifs found in plasma DNA. These aberrations were independent of anti-DNA response, suggesting that they represented a primary effect of DNASE1L3 loss. Pregnant Dnase1l3-/- mice carrying Dnase1l3+/- fetuses showed a partial restoration of normal frequencies of plasma DNA end motifs, suggesting that DNASE1L3 from Dnase1l3-proficient fetuses could enter maternal systemic circulation and affect both fetal and maternal DNA fragmentation in a systemic as well as local manner. However, the observed shortening of circulating fetal DNA relative to maternal DNA was not affected by the deletion of Dnase1l3 Collectively, our findings demonstrate that DNASE1L3 plays a role in circulating plasma DNA homeostasis by enhancing fragmentation and influencing end-motif frequencies. These results support a distinct role of DNASE1L3 as a regulator of the physical form and availability of cell-free DNA and may have important implications for the mechanism whereby this enzyme prevents autoimmunity.}, } @article {pmid30593562, year = {2019}, author = {Li, H and Shi, XQ and Huang, M and Chen, X and Xiao, M and Liu, C and Chaté, H and Zhang, HP}, title = {Data-driven quantitative modeling of bacterial active nematics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {777-785}, doi = {10.1073/pnas.1812570116}, pmid = {30593562}, issn = {1091-6490}, abstract = {Active matter comprises individual units that convert energy into mechanical motion. In many examples, such as bacterial systems and biofilament assays, constituent units are elongated and can give rise to local nematic orientational order. Such "active nematics" systems have attracted much attention from both theorists and experimentalists. However, despite intense research efforts, data-driven quantitative modeling has not been achieved, a situation mainly due to the lack of systematic experimental data and to the large number of parameters of current models. Here, we introduce an active nematics system made of swarming filamentous bacteria. We simultaneously measure orientation and velocity fields and show that the complex spatiotemporal dynamics of our system can be quantitatively reproduced by a type of microscopic model for active suspensions whose important parameters are all estimated from comprehensive experimental data. This provides unprecedented access to key effective parameters and mechanisms governing active nematics. Our approach is applicable to different types of dense suspensions and shows a path toward more quantitative active matter research.}, } @article {pmid30593561, year = {2019}, author = {Aryal, NK and Pant, V and Wasylishen, AR and Parker-Thornburg, J and Baseler, L and El-Naggar, AK and Liu, B and Kalia, A and Lozano, G and Arur, S}, title = {Constitutive Dicer1 phosphorylation accelerates metabolism and aging in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {960-969}, doi = {10.1073/pnas.1814377116}, pmid = {30593561}, issn = {1091-6490}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, abstract = {DICER1 gene alterations and decreased expression are associated with developmental disorders and diseases in humans. Oscillation of Dicer1 phosphorylation and dephosphorylation regulates its function during the oocyte-to-embryo transition in Caenorhabditis elegans Dicer1 is also phosphorylated upon FGF stimulation at conserved serines in mouse embryonic fibroblasts and HEK293 cells. However, whether phosphorylation of Dicer1 has a role in mammalian development remains unknown. To investigate the consequence of constitutive phosphorylation, we generated phosphomimetic knock-in mouse models by replacing conserved serines 1712 and 1836 with aspartic acids individually or together. Dicer1S1836D/S1836D mice display highly penetrant postnatal lethality, and the few survivors display accelerated aging and infertility. Homozygous dual-phosphomimetic Dicer1 augments these defects, alters metabolism-associated miRNAs, and causes a hypermetabolic phenotype. Thus, constitutive phosphorylation of Dicer1 results in multiple pathologic processes in mice, indicating that phosphorylation tightly regulates Dicer1 function and activity in mammals.}, } @article {pmid30593560, year = {2019}, author = {Xu, Q and Jin, X and Zheng, M and Rohila, D and Fu, G and Wen, Z and Lou, J and Wu, S and Sloan, R and Wang, L and Hu, H and Gao, X and Lu, L}, title = {Phosphatase PP2A is essential for TH17 differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {982-987}, doi = {10.1073/pnas.1807484116}, pmid = {30593560}, issn = {1091-6490}, abstract = {Phosphatase PP2A expression levels are positively correlated to the clinical severity of systemic lupus erythematosus (SLE) and IL17A cytokine overproduction, indicating a potential role of PP2A in controlling TH17 differentiation and inflammation. By generating a mouse strain with ablation of the catalytic subunit α of PP2A in peripheral mature T cells (PP2A cKO), we demonstrate that the PP2A complex is essential for TH17 differentiation. These PP2A cKO mice had reduced TH17 cell numbers and less severe disease in an experimental autoimmune encephalomyelitis (EAE) model. PP2A deficiency also ablated C-terminal phosphorylation of SMAD2 but increased C-terminal phosphorylation of SMAD3. By regulating the activity of RORγt via binding, the changes in the phosphorylation status of these R-SMADs reduced Il17a gene transcription. Finally, PP2A inhibitors showed similar effects on TH17 cells as were observed in PP2A cKO mice, i.e., decreased TH17 differentiation and relative protection of mice from EAE. Taken together, these data demonstrate that phosphatase PP2A is essential for TH17 differentiation and that inhibition of PP2A could be a possible therapeutic approach to controlling TH17-driven autoimmune diseases.}, } @article {pmid30593278, year = {2018}, author = {Coelho, MA and Li, S and Pane, LS and Firth, M and Ciotta, G and Wrigley, JD and Cuomo, ME and Maresca, M and Taylor, BJM}, title = {BE-FLARE: a fluorescent reporter of base editing activity reveals editing characteristics of APOBEC3A and APOBEC3B.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {150}, doi = {10.1186/s12915-018-0617-1}, pmid = {30593278}, issn = {1741-7007}, abstract = {BACKGROUND: Base Editing is a precise genome editing method that uses a deaminase-Cas9 fusion protein to mutate cytidine to thymidine in target DNA in situ without the generation of a double-strand break. However, the efficient enrichment of genetically modified cells using this technique is limited by the ability to detect such events.

RESULTS: We have developed a Base Editing FLuorescent Activity REporter (BE-FLARE), which allows for the enrichment of cells that have undergone editing of target loci based on a fluorescence shift from BFP to GFP. We used BE-FLARE to evaluate the editing efficiency of APOBEC3A and APOBEC3B family members as alternatives deaminase domains to the rat APOBEC1 domain used in base editor 3 (BE3). We identified human APOBEC3A and APOBEC3B as highly efficient cytidine deaminases for base editing applications with unique properties.

CONCLUSIONS: Using BE-FLARE to report on the efficiency and precision of editing events, we outline workflows for the accelerated generation of genetically engineered cell models and the discovery of alternative base editors.}, } @article {pmid30593269, year = {2018}, author = {Rahman, F and Hassan, M and Hanano, A and Fitzpatrick, DA and McCarthy, CGP and Murphy, DJ}, title = {Evolutionary, structural and functional analysis of the caleosin/peroxygenase gene family in the Fungi.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {976}, doi = {10.1186/s12864-018-5334-1}, pmid = {30593269}, issn = {1471-2164}, abstract = {BACKGROUND: Caleosin/peroxygenases, CLO/PXG, (designated PF05042 in Pfam) are a group of genes/proteins with anomalous distributions in eukaryotic taxa. We have previously characterised CLO/PXGs in the Viridiplantae. The aim of this study was to investigate the evolution and functions of the CLO/PXGs in the Fungi and other non-plant clades and to elucidate the overall origin of this gene family.

RESULTS: CLO/PXG-like genes are distributed across the full range of fungal groups from the basal clades, Cryptomycota and Microsporidia, to the largest and most complex Dikarya species. However, the genes were only present in 243 out of 844 analysed fungal genomes. CLO/PXG-like genes have been retained in many pathogenic or parasitic fungi that have undergone considerable genomic and structural simplification, indicating that they have important functions in these species. Structural and functional analyses demonstrate that CLO/PXGs are multifunctional proteins closely related to similar proteins found in all major taxa of the Chlorophyte Division of the Viridiplantae. Transcriptome and physiological data show that fungal CLO/PXG-like genes have complex patterns of developmental and tissue-specific expression and are upregulated in response to a range of biotic and abiotic stresses as well as participating in key metabolic and developmental processes such as lipid metabolism, signalling, reproduction and pathogenesis. Biochemical data also reveal that the Aspergillus flavus CLO/PXG has specific functions in sporulation and aflatoxin production as well as playing roles in lipid droplet function.

CONCLUSIONS: In contrast to plants, CLO/PXGs only occur in about 30% of sequenced fungal genomes but are present in all major taxa. Fungal CLO/PXGs have similar but not identical roles to those in plants, including stress-related oxylipin signalling, lipid metabolism, reproduction and pathogenesis. While the presence of CLO/PXG orthologs in all plant genomes sequenced to date would suggest that they have core housekeeping functions in plants, the selective loss of CLO/PXGs in many fungal genomes suggests more restricted functions in fungi as accessory genes useful in particular environments or niches. We suggest an ancient origin of CLO/PXG-like genes in the 'last eukaryotic common ancestor' (LECA) and their subsequent loss in ancestors of the Metazoa, after the latter had diverged from the ancestral fungal lineage.}, } @article {pmid30593266, year = {2018}, author = {Zhang, C and He, X and Kwok, YK and Wang, F and Xue, J and Zhao, H and Suen, KW and Wang, CC and Ren, J and Chen, GG and Lai, PBS and Li, J and Xia, Y and Chan, AM and Chan, WY and Feng, B}, title = {Homology-independent multiallelic disruption via CRISPR/Cas9-based knock-in yields distinct functional outcomes in human cells.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {151}, doi = {10.1186/s12915-018-0616-2}, pmid = {30593266}, issn = {1741-7007}, abstract = {BACKGROUND: Cultured human cells are pivotal models to study human gene functions, but introducing complete loss of function in diploid or aneuploid cells has been a challenge. The recently developed CRISPR/Cas9-mediated homology-independent knock-in approach permits targeted insertion of large DNA at high efficiency, providing a tool for insertional disruption of a selected gene. Pioneer studies have showed promising results, but the current methodology is still suboptimal and functional outcomes have not been well examined. Taking advantage of the promoterless fluorescence reporter systems established in our previous study, here, we further investigated potentials of this new insertional gene disruption approach and examined its functional outcomes.

RESULTS: Exemplified by using hyperploid LO2 cells, we demonstrated that simultaneous knock-in of dual fluorescence reporters through CRISPR/Cas9-induced homology-independent DNA repair permitted one-step generation of cells carrying complete disruption of target genes at multiple alleles. Through knocking-in at coding exons, we generated stable single-cell clones carrying complete disruption of ULK1 gene at all four alleles, lacking intact FAT10 in all three alleles, or devoid of intact CtIP at both alleles. We have confirmed the depletion of ULK1 and FAT10 transcripts as well as corresponding proteins in the obtained cell clones. Moreover, consistent with previous reports, we observed impaired mitophagy in ULK1-/- cells and attenuated cytokine-induced cell death in FAT10-/- clones. However, our analysis showed that single-cell clones carrying complete disruption of CtIP gene at both alleles preserved in-frame aberrant CtIP transcripts and produced proteins. Strikingly, the CtIP-disrupted clones raised through another two distinct targeting strategies also produced varied but in-frame aberrant CtIP transcripts. Sequencing analysis suggested that diverse DNA processing and alternative RNA splicing were involved in generating these in-frame aberrant CtIP transcripts, and some infrequent events were biasedly enriched among the CtIP-disrupted cell clones.

CONCLUSION: Multiallelic gene disruption could be readily introduced through CRISPR/Cas9-induced homology-independent knock-in of dual fluorescence reporters followed by direct tracing and cell isolation. Robust cellular mechanisms exist to spare essential genes from loss-of-function modifications, by generating partially functional transcripts through diverse DNA and RNA processing mechanisms.}, } @article {pmid30593264, year = {2018}, author = {Li, Q and Yang, C and Du, J and Zhang, B and He, Y and Hu, Q and Li, M and Zhang, Y and Wang, C and Zhong, J}, title = {Characterization of miRNA profiles in the mammary tissue of dairy cattle in response to heat stress.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {975}, doi = {10.1186/s12864-018-5298-1}, pmid = {30593264}, issn = {1471-2164}, support = {31402056//National Natural Science Foundation of China/ ; BJ2014048//Youth Talent Project in Hebei Province/ ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) are a class of small noncoding RNAs that play important roles in the regulation of gene expression. However, the role of miRNAs in bovine mammary gland responses to heat stress is not well understood.

RESULTS: In the present study, we performed a deep RNA sequencing analysis to identify miRNAs associated with the heat stress potential of the bovine mammary gland. We identified 27 miRNAs that were differentially expressed significantly between the mammary tissue of Holstein cattle heat stress and normal conditions. Twenty miRNAs had higher expression in the mammary tissue of heat-stressed Holstein cattle. The seven highest differentially expressed candidate miRNAs (bta-miR-21-5p, bta-miR-99a-5p, bta-miR-146b, bta-miR-145, bta-miR-2285 t, bta-miR-133a, and bta-miR-29c) identified by deep RNA sequencing were additionally evaluated by stem-loop qPCR. Enrichment analyses for targeted genes revealed that the major differences between miRNAs expression in the mammary gland of heat-stressed versus control were associated with the regulation of Wnt, TGF-β, MAPK, Notch, and JAK-STAT.

CONCLUSIONS: These data indicated that the differentially expressed miRNAs identified in this study may act as dominant regulators during heat stress. We might reduce heat stress damage of Holstein cows by up-regulating or down-regulating these differentially expressed miRNAs.}, } @article {pmid30592536, year = {2018}, author = {Leftwich, PT and Nash, WJ and Friend, LA and Chapman, T}, title = {Contribution of maternal effects to dietary selection in Mediterranean fruit flies.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13664}, pmid = {30592536}, issn = {1558-5646}, support = {//Natural Environment Research Council/ ; BB/K000489/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Individual responses to dietary variation represent a fundamental component of fitness, and nutritional adaptation can occur over just a few generations. Maternal effects can show marked proximate responses to nutrition, but whether they contribute to longer term dietary adaptation is unclear. Here, we tested the hypotheses that maternal effects: (i) contribute to dietary adaptation, (ii) diminish when dietary conditions are constant between generations, (iii) are trait-specific and (iv) interact with high- and low-quality food. We used experimental evolution regimes in the medfly (Ceratitis capitata) to test these predictions by subjecting an outbred laboratory-adapted population to replicated experimental evolution on either constant high calorie sugar ('A') or low-calorie starch ('S') larval diets, with a standard adult diet across both regimes. We measured the contribution of maternal effects by comparing developmental and adult phenotypes of individuals reared on their own diet with those swapped onto the opposite diet for either one or two generations (high and low maternal effect conditions, respectively), both at the start and after 30 generations of selection. Initially, there were strong maternal effects on female body mass and male mating success but not larval survival. Interestingly, the initial maternal effects observed in female body mass and male mating success showed sex-specific interactions when individuals from high calorie regimes were tested on low calorie diets. However, as populations responded to selection, the effects of maternal provisioning on all traits diminished. The results broadly supported the predictions. They show how the contribution of maternal effects to dietary responses evolves in a context-dependent manner, with significant variation across different fitness-related traits. We conclude that maternal effects can evolve during nutritional adaptation and hence may be an important life history trait to measure, rather than to routinely minimize.}, } @article {pmid30592533, year = {2018}, author = {Burress, ED and Wainwright, PC}, title = {Adaptive radiation in labrid fishes: A central role for functional innovations during 65 My of relentless diversification.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13670}, pmid = {30592533}, issn = {1558-5646}, support = {DEB-0717009//National Science Foundation/ ; DEB-1061981//National Science Foundation/ ; }, abstract = {Early burst patterns of diversification have become closely linked with concepts of adaptive radiation, reflecting interest in the role of ecological opportunity in modulating diversification. But, this model has not been widely explored on coral reefs, where biodiversity is exceptional, but many lineages have high dispersal capabilities and a pan-tropical distribution. We analyze adaptive radiation in labrid fishes, arguably the most ecologically dominant and diverse radiation of fishes on coral reefs. We test for time-dependent speciation, trophic diversification, and origination of 15 functional innovations, and early bursts in a series of functional morphological traits associated with feeding and locomotion. We find no evidence of time-dependent or early burst evolution. Instead, the pace of speciation, ecological diversification, and trait evolution has been relatively constant. The origination of functional innovations has slowed over time, although few arose early. The labrid radiation seems to have occurred in response to extensive and still increasing ecological opportunity, but within a rich community of antagonists that may have prevented abrupt diversification. Labrid diversification is closely tied to a series of substantial functional innovations that individually broadened ecological diversity, ultimately allowing them to invade virtually every trophic niche held by fishes on coral reefs.}, } @article {pmid30592527, year = {2018}, author = {Hu, XS and Zhang, XX and Zhou, W and Hu, Y and Wang, X and Chen, XY}, title = {Mating system shifts a species' range.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13663}, pmid = {30592527}, issn = {1558-5646}, support = {4400-K16013//South China Agricultural University/ ; 2015KJCV009//Forest Sciences and Technology Innovation Project in Guangdong Province/ ; }, abstract = {Understanding the ecological and evolutionary mechanisms that shape a species' range is an important goal in evolutionary biology. Evidence indicates that mating system is an effective predictor of the global range of native species or naturalized alien plants, but the mechanisms underlying this predictability are not elaborated. Here, we develop a theoretical model to account for the ranges of plants under different mating systems based on migration-selection processes (an idea proposed by Haldane). The model includes alternation of gametophyte and sporophyte generations in one life cycle and the dispersal of haploid pollen and diploid seeds as vectors for gene flow. We show that the interaction between selfing rates and gametophytic selection determines the role of mating system in shaping a species' range. Selfing restricts the species' range under gametophytic selection in nonrandom mating systems, but expands the species' range under the absence of gametophytic selection in any mating system. Gametophytic selection slightly restricts the species' range in random mating. Both logarithmic and logistic models of population demography yield similar conclusions in the case of fixed or evolving genetic variance. The theory also helps to explain a broader relationship between mating system and range size following biological invasion or plant naturalization.}, } @article {pmid30592143, year = {2018}, author = {Apari, P and Müller, V}, title = {Paradoxes of tumour complexity: somatic selection, vulnerability by design, or infectious aetiology?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12490}, pmid = {30592143}, issn = {1469-185X}, support = {GINOP-2.3.2-15-2016-00057 ("Az evolúció fény//Hungarian Ministry of Human Capacities/ ; 1783-3/2018/FEKUTSRAT//ELTE Institutional Excellence Program/ ; Bolyai János Research Fellowship//Magyar Tudományos Akadémia/ ; //National Research, Development and Innovation Office of Hungary/ ; }, abstract = {The aetiology of cancer involves intricate cellular and molecular mechanisms that apparently emerge on the short timescale of a single lifetime. Some of these traits are remarkable not only for their complexity, but also because it is hard to conceive selection pressures that would favour their evolution within the local competitive microenvironment of the tumour. Examples include 'niche construction' (re-programming of tumour-specific target sites) to create permissive conditions for distant metastases; long-range feedback loops of tumour growth; and remarkably 'plastic' phenotypes (e.g. density-dependent dispersal) associated with metastatic cancer. These traits, which we term 'paradoxical tumour traits', facilitate the long-range spread or long-term persistence of the tumours, but offer no apparent benefit, and might even incur costs in the competition of clones within the tumour. We discuss three possible scenarios for the origin of these characters: somatic selection driven by specific selection regimes; non-adaptive emergence due to inherent vulnerabilities in the organism; and manipulation by putative transmissible agents that contribute to and benefit from these traits. Our work highlights a lack of understanding of some aspects of tumour development, and offers alternative hypotheses that might guide further research.}, } @article {pmid30592124, year = {2018}, author = {Wang, Y and Huang, JM and Cui, GJ and Nunoura, T and Takaki, Y and Li, WL and Li, J and Gao, ZM and Takai, K and Zhang, AQ and Stepanauskas, R}, title = {Genomics insights into ecotype formation of ammonia-oxidizing archaea in the deep ocean.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14518}, pmid = {30592124}, issn = {1462-2920}, support = {EF-0826924//NSF/ ; OCE-1335810//NSF/ ; OCE-1232982//NSF/ ; 30070015//Japan Society for the Promotion of Science/ ; 2016YFC0302500//Research and Development/ ; XDB06040101//Chinese Academy of Sciences/ ; XDB06010201//Chinese Academy of Sciences/ ; 31460001//National Science Foundation of China/ ; 41476104//National Science Foundation of China/ ; }, abstract = {Various lineages of ammonia-oxidizing archaea (AOA) are present in deep waters, but the mechanisms that determine ecotype formation are obscure. We studied 18 high-quality genomes of the marine group I AOA lineages (alpha, gamma and delta) from the Mariana and Ogasawara trenches. The genomes of alpha AOA resembled each other, while those of gamma and delta lineages were more divergent and had even undergone insertion of some phage genes. The instability of the gamma and delta AOA genomes could be partially due to the loss of DNA polymerase B (polB) and methyladenine DNA glycosylase (tag) genes responsible for the repair of point mutations. The alpha AOA genomes harbour genes encoding a thrombospondin-like outer membrane structure that probably serves as a barrier to gene flow. Moreover, the gamma and alpha AOA lineages rely on vitamin B12 -independent MetE and B12 -dependent MetH, respectively, for methionine synthesis. The delta AOA genome contains genes involved in uptake of sugar and peptide perhaps for heterotrophic lifestyle. Our study provides insights into co-occurrence of cladogenesis and anagenesis in the formation of AOA ecotypes that perform differently in nitrogen and carbon cycling in dark oceans.}, } @article {pmid30592040, year = {2018}, author = {Araya-Ajoy, YG and Ranke, PS and Kvalnes, T and Rønning, B and Holand, H and Myhre, AM and Pärn, H and Jensen, H and Ringsby, TH and Saether, BE and Wright, J}, title = {Characterizing morphological (co)variation using structural equation models: Body size, allometric relationships and evolvability in a house sparrow metapopulation.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13668}, pmid = {30592040}, issn = {1558-5646}, support = {191847//Norwegian Research Council/ ; 274930//Norwegian Research Council/ ; 221956//Norwegian Research Council/ ; 223257//Research Council of Norway/ ; //Norwegian Directorate for Nature Management and the EU-commission/ ; }, abstract = {Body size plays a key role in the ecology and evolution of all organisms. Therefore, quantifying the sources of morphological (co)variation, dependent and independent of body size, is of key importance when trying to understand and predict responses to selection. We combine structural equation modeling with quantitative genetics analyses to study morphological (co)variation in a meta-population of house sparrows (Passer domesticus). As expected, we found evidence of a latent variable "body size," causing genetic and environmental covariation between morphological traits. Estimates of conditional evolvability show that allometric relationships constrain the independent evolution of house sparrow morphology. We also found spatial differences in general body size and its allometric relationships. On islands where birds are more dispersive and mobile, individuals were smaller and had proportionally longer wings for their body size. Although on islands where sparrows are more sedentary and nest in dense colonies, individuals were larger and had proportionally longer tarsi for their body size. We corroborated these results using simulations and show that our analyses produce unbiased allometric slope estimates. This study highlights that in the short term allometric relationships may constrain phenotypic evolution, but that in the long term selection pressures can also shape allometric relationships.}, } @article {pmid30592037, year = {2018}, author = {Richards, TJ}, title = {Digest: All genomes are not equal: How variation in autosomal, sex chromosome, and mitochondrial genomes contributes to the process of local adaptation.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13667}, pmid = {30592037}, issn = {1558-5646}, abstract = {Which genome contributes most to patterns of adaptive trait divergence in Drosophila melanogaster across environmental clines? In this issue, Lasne et al. find that genetic variation associated with adaptive traits is mostly distributed between autosomal and mitochondrial genomes with a negligible contribution from the X chromosome.}, } @article {pmid30592035, year = {2018}, author = {Richards, TJ}, title = {Digest: Adaptation and isolation: Testing genetic and environmental barriers to hybridization in Silene.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13665}, pmid = {30592035}, issn = {1558-5646}, abstract = {Species differences are maintained by the cumulative effect of factors that reduce gene flow between divergent lineages. In this issue, Karrenberg et al. quantify multiple genetic and environmental barriers to gene exchange between two closely related plant species and find that adaptation to divergent environments has the greatest effect on reproductive isolation.}, } @article {pmid30591570, year = {2019}, author = {De Mets, F and Van Melderen, L and Gottesman, S}, title = {Regulation of acetate metabolism and coordination with the TCA cycle via a processed small RNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {1043-1052}, doi = {10.1073/pnas.1815288116}, pmid = {30591570}, issn = {1091-6490}, abstract = {Bacterial regulatory small RNAs act as crucial regulators in central carbon metabolism by modulating translation initiation and degradation of target mRNAs in metabolic pathways. Here, we demonstrate that a noncoding small RNA, SdhX, is produced by RNase E-dependent processing from the 3'UTR of the sdhCDAB-sucABCD operon, encoding enzymes of the tricarboxylic acid (TCA) cycle. In Escherichia coli, SdhX negatively regulates ackA, which encodes an enzyme critical for degradation of the signaling molecule acetyl phosphate, while the downstream pta gene, encoding the enzyme critical for acetyl phosphate synthesis, is not significantly affected. This discoordinate regulation of pta and ackA increases the accumulation of acetyl phosphate when SdhX is expressed. Mutations in sdhX that abolish regulation of ackA lead to more acetate in the medium (more overflow metabolism), as well as a strong growth defect in the presence of acetate as sole carbon source, when the AckA-Pta pathway runs in reverse. SdhX overproduction confers resistance to hydroxyurea, via regulation of ackA SdhX abundance is tightly coupled to the transcription signals of TCA cycle genes but escapes all known posttranscriptional regulation. Therefore, SdhX expression directly correlates with transcriptional input to the TCA cycle, providing an effective mechanism for the cell to link the TCA cycle with acetate metabolism pathways.}, } @article {pmid30591569, year = {2019}, author = {Davidovitch, B and Sun, Y and Grason, GM}, title = {Geometrically incompatible confinement of solids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {5}, pages = {1483-1488}, doi = {10.1073/pnas.1815507116}, pmid = {30591569}, issn = {1091-6490}, abstract = {The complex morphologies exhibited by spatially confined thin objects have long challenged human efforts to understand and manipulate them, from the representation of patterns in draped fabric in Renaissance art to current-day efforts to engineer flexible sensors that conform to the human body. We introduce a theoretical principle, broadly generalizing Euler's elastica-a core concept of continuum mechanics that invokes the energetic preference of bending over straining a thin solid object and that has been widely applied to classical and modern studies of beams and rods. We define a class of geometrically incompatible confinement problems, whereby the topography imposed on a thin solid body is incompatible with its intrinsic ("target") metric and, as a consequence of Gauss' Theorema Egregium, induces strain. By focusing on a prototypical example of a sheet attached to a spherical substrate, numerical simulations and analytical study demonstrate that the mechanics is governed by a principle, which we call the "Gauss-Euler elastica" This emergent rule states that-despite the unavoidable strain in such an incompatible confinement-the ratio between the energies stored in straining and bending the solid may be arbitrarily small. The Gauss-Euler elastica underlies a theoretical framework that greatly simplifies the daunting task of solving the highly nonlinear equations that describe thin solids at mechanical equilibrium. This development thus opens possibilities for attacking a broad class of phenomena governed by the coupling of geometry and mechanics.}, } @article {pmid30591568, year = {2019}, author = {Wang, H and Qi, J and Zhang, S and Li, Y and Tan, S and Gao, GF}, title = {Binding mode of the side-by-side two-IgV molecule CD226/DNAM-1 to its ligand CD155/Necl-5.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {988-996}, doi = {10.1073/pnas.1815716116}, pmid = {30591568}, issn = {1091-6490}, abstract = {Natural killer (NK) cells are important component of innate immunity and also contribute to activating and reshaping the adaptive immune responses. The functions of NK cells are modulated by multiple inhibitory and stimulatory receptors. Among these receptors, the activating receptor CD226 (DNAM-1) mediates NK cell activation via binding to its nectin-like (Necl) family ligand, CD155 (Necl-5). Here, we present a unique side-by-side arrangement pattern of two tandem immunoglobulin V-set (IgV) domains deriving from the ectodomains of both human CD226 (hCD226-ecto) and mouse CD226 (mCD226-ecto), which is substantially different from the conventional head-to-tail arrangement of other multiple Ig-like domain molecules. The hybrid complex structure of mCD226-ecto binding to the first domain of human CD155 (hCD155-D1) reveals a conserved binding interface with the first domain of CD226 (D1), whereas the second domain of CD226 (D2) both provides structural supports for the unique architecture of CD226 and forms direct interactions with CD155. In the absence of the D2 domain, CD226-D1 exhibited substantially reduced binding efficacy to CD155. Collectively, these findings would broaden our knowledge of the interaction between NK cell receptors and the nectin/Necl family ligands, as well as provide molecular basis for the development of CD226-targeted antitumor immunotherapeutics.}, } @article {pmid30591567, year = {2019}, author = {De Magis, A and Manzo, SG and Russo, M and Marinello, J and Morigi, R and Sordet, O and Capranico, G}, title = {DNA damage and genome instability by G-quadruplex ligands are mediated by R loops in human cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {816-825}, doi = {10.1073/pnas.1810409116}, pmid = {30591567}, issn = {1091-6490}, abstract = {G quadruplexes (G4s) and R loops are noncanonical DNA structures that can regulate basic nuclear processes and trigger DNA damage, genome instability, and cell killing. By different technical approaches, we here establish that specific G4 ligands stabilize G4s and simultaneously increase R-loop levels within minutes in human cancer cells. Genome-wide mapping of R loops showed that the studied G4 ligands likely cause the spreading of R loops to adjacent regions containing G4 structures, preferentially at 3'-end regions of expressed genes, which are partially ligand-specific. Overexpression of an exogenous human RNaseH1 rescued DNA damage induced by G4 ligands in BRCA2-proficient and BRCA2-silenced cancer cells. Moreover, even if the studied G4 ligands increased noncanonical DNA structures at similar levels in nuclear chromatin, their cellular effects were different in relation to cell-killing activity and stimulation of micronuclei, a hallmark of genome instability. Our findings therefore establish that G4 ligands can induce DNA damage by an R loop-dependent mechanism that can eventually lead to different cellular consequences depending on the chemical nature of the ligands.}, } @article {pmid30591566, year = {2019}, author = {Yadavalli, SS and Xiao, Q and Sherman, SE and Hasley, WD and Klein, ML and Goulian, M and Percec, V}, title = {Bioactive cell-like hybrids from dendrimersomes with a human cell membrane and its components.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {744-752}, doi = {10.1073/pnas.1811307116}, pmid = {30591566}, issn = {1091-6490}, support = {R01 GM080279/GM/NIGMS NIH HHS/United States ; }, abstract = {Cell-like hybrids from natural and synthetic amphiphiles provide a platform to engineer functions of synthetic cells and protocells. Cell membranes and vesicles prepared from human cell membranes are relatively unstable in vitro and therefore are difficult to study. The thicknesses of biological membranes and vesicles self-assembled from amphiphilic Janus dendrimers, known as dendrimersomes, are comparable. This feature facilitated the coassembly of functional cell-like hybrid vesicles from giant dendrimersomes and bacterial membrane vesicles generated from the very stable bacterial Escherichia coli cell after enzymatic degradation of its outer membrane. Human cells are fragile and require only mild centrifugation to be dismantled and subsequently reconstituted into vesicles. Here we report the coassembly of human membrane vesicles with dendrimersomes. The resulting giant hybrid vesicles containing human cell membranes, their components, and Janus dendrimers are stable for at least 1 y. To demonstrate the utility of cell-like hybrid vesicles, hybrids from dendrimersomes and bacterial membrane vesicles containing YadA, a bacterial adhesin protein, were prepared. The latter cell-like hybrids were recognized by human cells, allowing for adhesion and entry of the hybrid bacterial vesicles into human cells in vitro.}, } @article {pmid30591565, year = {2019}, author = {Lei, J and Sheng, G and Cheung, PP and Wang, S and Li, Y and Gao, X and Zhang, Y and Wang, Y and Huang, X}, title = {Two symmetric arginine residues play distinct roles in Thermus thermophilus Argonaute DNA guide strand-mediated DNA target cleavage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {845-853}, doi = {10.1073/pnas.1817041116}, pmid = {30591565}, issn = {1091-6490}, support = {R35 GM127040/GM/NIGMS NIH HHS/United States ; }, abstract = {Bacterium Thermus thermophilus Argonaute (Ago; TtAgo) is a prokaryotic Ago (pAgo) that acts as the host defense against the uptake and propagation of foreign DNA by catalyzing the DNA cleavage reaction. The TtAgo active site consists of a plugged-in glutamate finger with two arginine residues (R545 and R486) located symmetrically around it. An interesting challenge is to understand how they can collaboratively facilitate enzymatic catalysis. In Kluyveromyces polysporus Ago, a eukaryotic Ago, the evolutionarily symmetrical residues are arginine and histidine, both of which function to stabilize the plugged-in catalytic tetrad conformation. Surprisingly, our simulation results indicated that, in TtAgo, only R545 is involved in the cleavage reaction by serving as a critical structural anchor to stabilize the catalytic tetrad Asp-Glu-Asp-Asp that is completed by the insertion of the glutamate finger, whereas R486 is not involved in target cleavage. The TtAgo-mediated target DNA cleavage occurs in a substrate-assisted mechanism, in which the pro-Rp (Rp, a tetrahedral phosphorus center with "R-type" chirality) oxygen of scissile phosphate acts as a general base to activate the nucleophilic water. Our unexpected theoretical findings on distinct roles played by R545 and R486 in TtAgo catalysis have been validated by single-point site-mutagenesis experiments, wherein the target cleavage is abolished for all mutants of R545. In sharp contrast, the cleavage activity is maintained for all mutants of R486. Our work provides mechanistic insights on the catalytic specificity of Ago proteins and could facilitate the design of new gene-editing tools in the long term.}, } @article {pmid30591564, year = {2019}, author = {Li, Y and Führer, M and Bahrami, E and Socha, P and Klaudel-Dreszler, M and Bouzidi, A and Liu, Y and Lehle, AS and Magg, T and Hollizeck, S and Rohlfs, M and Conca, R and Field, M and Warner, N and Mordechai, S and Shteyer, E and Turner, D and Boukari, R and Belbouab, R and Walz, C and Gaidt, MM and Hornung, V and Baumann, B and Pannicke, U and Al Idrissi, E and Ali Alghamdi, H and Sepulveda, FE and Gil, M and de Saint Basile, G and Hönig, M and Koletzko, S and Muise, AM and Snapper, SB and Schwarz, K and Klein, C and Kotlarz, D}, title = {Human RIPK1 deficiency causes combined immunodeficiency and inflammatory bowel diseases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {970-975}, doi = {10.1073/pnas.1813582116}, pmid = {30591564}, issn = {1091-6490}, abstract = {Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is a critical regulator of cell death and inflammation, but its relevance for human disease pathogenesis remains elusive. Studies of monogenic disorders might provide critical insights into disease mechanisms and therapeutic targeting of RIPK1 for common diseases. Here, we report on eight patients from six unrelated pedigrees with biallelic loss-of-function mutations in RIPK1 presenting with primary immunodeficiency and/or intestinal inflammation. Mutations in RIPK1 were associated with reduced NF-κB activity, defective differentiation of T and B cells, increased inflammasome activity, and impaired response to TNFR1-mediated cell death in intestinal epithelial cells. The characterization of RIPK1-deficient patients highlights the essential role of RIPK1 in controlling human immune and intestinal homeostasis, and might have critical implications for therapies targeting RIPK1.}, } @article {pmid30591563, year = {2019}, author = {Lindenmayer, D}, title = {Small patches make critical contributions to biodiversity conservation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {717-719}, doi = {10.1073/pnas.1820169116}, pmid = {30591563}, issn = {1091-6490}, } @article {pmid30591562, year = {2019}, author = {Zeng, G and Li, D and Guo, S and Gao, L and Gao, Z and Stanley, HE and Havlin, S}, title = {Switch between critical percolation modes in city traffic dynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {23-28}, doi = {10.1073/pnas.1801545116}, pmid = {30591562}, issn = {1091-6490}, abstract = {Percolation transition is widely observed in networks ranging from biology to engineering. While much attention has been paid to network topologies, studies rarely focus on critical percolation phenomena driven by network dynamics. Using extensive real data, we study the critical percolation properties in city traffic dynamics. Our results suggest that two modes of different critical percolation behaviors are switching in the same network topology under different traffic dynamics. One mode of city traffic (during nonrush hours or days off) has similar critical percolation characteristics as small world networks, while the other mode (during rush hours on working days) tends to behave as a 2D lattice. This switching behavior can be understood by the fact that the high-speed urban roads during nonrush hours or days off (that are congested during rush hours) represent effective long-range connections, like in small world networks. Our results might be useful for understanding and improving traffic resilience.}, } @article {pmid30591561, year = {2019}, author = {MacEachern, S}, title = {States and their genetic consequences in central Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {356-357}, doi = {10.1073/pnas.1819609116}, pmid = {30591561}, issn = {1091-6490}, } @article {pmid30591560, year = {2019}, author = {Caldeira, K and Brown, PT}, title = {Reduced emissions through climate damage to the economy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {714-716}, doi = {10.1073/pnas.1819605116}, pmid = {30591560}, issn = {1091-6490}, } @article {pmid30591559, year = {2019}, author = {Zhang, Y and Wang, X and Zhang, X and Wang, J and Ma, Y and Zhang, L and Cao, X}, title = {RNA-binding protein YTHDF3 suppresses interferon-dependent antiviral responses by promoting FOXO3 translation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {976-981}, doi = {10.1073/pnas.1812536116}, pmid = {30591559}, issn = {1091-6490}, abstract = {IFN-stimulated genes (ISGs) are essential effectors of the IFN-dependent antiviral immune response. Dysregulation of ISG expression can cause dysfunctional antiviral responses and autoimmune disorders. Epitranscriptomic regulation, such as N6-methyladenosine (m6A) modification of mRNAs, plays key roles in diverse biological processes. Here, we found that the m6A "reader" YT521-B homology domain-containing family 3 (YTHDF3) suppresses ISG expression under basal conditions by promoting translation of the transcription corepressor forkhead box protein O3 (FOXO3). YTHDF3 cooperates with two cofactors, PABP1 and eIF4G2, to promote FOXO3 translation by binding to the translation initiation region of FOXO3 mRNA. Both the YTH and the P/Q/N-rich domains of YTHDF3 were required for FOXO3 RNA-binding capacity, however, METTL3-mediated m6A modification was not involved in the process observed. Moreover, YTHDF3-/- mice had increased ISG levels and were resistant to several viral infections. Our findings uncover the role of YTHDF3 as a negative regulator of antiviral immunity through the translational promotion of FOXO3 mRNA under homeostatic conditions, adding insight into the networks of RNA-binding protein-RNA interactions in homeostatically maintaining host antiviral immune function and preventing inflammatory response.}, } @article {pmid30591558, year = {2019}, author = {Perry, NA and Kaoud, TS and Ortega, OO and Kaya, AI and Marcus, DJ and Pleinis, JM and Berndt, S and Chen, Q and Zhan, X and Dalby, KN and Lopez, CF and Iverson, TM and Gurevich, VV}, title = {Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {810-815}, doi = {10.1073/pnas.1819230116}, pmid = {30591558}, issn = {1091-6490}, support = {R21 DA043680/DA/NIDA NIH HHS/United States ; U01 CA215845/CA/NCI NIH HHS/United States ; R01 GM120569/GM/NIGMS NIH HHS/United States ; R01 GM123252/GM/NIGMS NIH HHS/United States ; R01 GM077561/GM/NIGMS NIH HHS/United States ; R01 GM109955/GM/NIGMS NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; R35 GM122491/GM/NIGMS NIH HHS/United States ; }, abstract = {Scaffold proteins tether and orient components of a signaling cascade to facilitate signaling. Although much is known about how scaffolds colocalize signaling proteins, it is unclear whether scaffolds promote signal amplification. Here, we used arrestin-3, a scaffold of the ASK1-MKK4/7-JNK3 cascade, as a model to understand signal amplification by a scaffold protein. We found that arrestin-3 exhibited >15-fold higher affinity for inactive JNK3 than for active JNK3, and this change involved a shift in the binding site following JNK3 activation. We used systems biochemistry modeling and Bayesian inference to evaluate how the activation of upstream kinases contributed to JNK3 phosphorylation. Our combined experimental and computational approach suggested that the catalytic phosphorylation rate of JNK3 at Thr-221 by MKK7 is two orders of magnitude faster than the corresponding phosphorylation of Tyr-223 by MKK4 with or without arrestin-3. Finally, we showed that the release of activated JNK3 was critical for signal amplification. Collectively, our data suggest a "conveyor belt" mechanism for signal amplification by scaffold proteins. This mechanism informs on a long-standing mystery for how few upstream kinase molecules activate numerous downstream kinases to amplify signaling.}, } @article {pmid30591557, year = {2019}, author = {Maffucci, P and Bigio, B and Rapaport, F and Cobat, A and Borghesi, A and Lopez, M and Patin, E and Bolze, A and Shang, L and Bendavid, M and Scott, EM and Stenson, PD and Cunningham-Rundles, C and Cooper, DN and Gleeson, JG and Fellay, J and Quintana-Murci, L and Casanova, JL and Abel, L and Boisson, B and Itan, Y}, title = {Blacklisting variants common in private cohorts but not in public databases optimizes human exome analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {950-959}, doi = {10.1073/pnas.1808403116}, pmid = {30591557}, issn = {1091-6490}, support = {U24 AI086037/AI/NIAID NIH HHS/United States ; R37 AI095983/AI/NIAID NIH HHS/United States ; R01 AI088364/AI/NIAID NIH HHS/United States ; P01 AI061093/AI/NIAID NIH HHS/United States ; R18 AI048693/AI/NIAID NIH HHS/United States ; R01 AI127564/AI/NIAID NIH HHS/United States ; T32 GM007280/GM/NIGMS NIH HHS/United States ; }, abstract = {Computational analyses of human patient exomes aim to filter out as many nonpathogenic genetic variants (NPVs) as possible, without removing the true disease-causing mutations. This involves comparing the patient's exome with public databases to remove reported variants inconsistent with disease prevalence, mode of inheritance, or clinical penetrance. However, variants frequent in a given exome cohort, but absent or rare in public databases, have also been reported and treated as NPVs, without rigorous exploration. We report the generation of a blacklist of variants frequent within an in-house cohort of 3,104 exomes. This blacklist did not remove known pathogenic mutations from the exomes of 129 patients and decreased the number of NPVs remaining in the 3,104 individual exomes by a median of 62%. We validated this approach by testing three other independent cohorts of 400, 902, and 3,869 exomes. The blacklist generated from any given cohort removed a substantial proportion of NPVs (11-65%). We analyzed the blacklisted variants computationally and experimentally. Most of the blacklisted variants corresponded to false signals generated by incomplete reference genome assembly, location in low-complexity regions, bioinformatic misprocessing, or limitations inherent to cohort-specific private alleles (e.g., due to sequencing kits, and genetic ancestries). Finally, we provide our precalculated blacklists, together with ReFiNE, a program for generating customized blacklists from any medium-sized or large in-house cohort of exome (or other next-generation sequencing) data via a user-friendly public web server. This work demonstrates the power of extracting variant blacklists from private databases as a specific in-house but broadly applicable tool for optimizing exome analysis.}, } @article {pmid30591209, year = {2018}, author = {Pontarp, M and Bunnefeld, L and Cabral, JS and Etienne, RS and Fritz, SA and Gillespie, R and Graham, CH and Hagen, O and Hartig, F and Huang, S and Jansson, R and Maliet, O and Münkemüller, T and Pellissier, L and Rangel, TF and Storch, D and Wiegand, T and Hurlbert, AH}, title = {The Latitudinal Diversity Gradient: Novel Understanding through Mechanistic Eco-evolutionary Models.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2018.11.009}, pmid = {30591209}, issn = {1872-8383}, abstract = {The latitudinal diversity gradient (LDG) is one of the most widely studied patterns in ecology, yet no consensus has been reached about its underlying causes. We argue that the reasons for this are the verbal nature of existing hypotheses, the failure to mechanistically link interacting ecological and evolutionary processes to the LDG, and the fact that empirical patterns are often consistent with multiple explanations. To address this issue, we synthesize current LDG hypotheses, uncovering their eco-evolutionary mechanisms, hidden assumptions, and commonalities. Furthermore, we propose mechanistic eco-evolutionary modeling and an inferential approach that makes use of geographic, phylogenetic, and trait-based patterns to assess the relative importance of different processes for generating the LDG.}, } @article {pmid30591074, year = {2018}, author = {Moges, Y and Hailu, T and Dimtsu, B and Yohannes, Z and Kelkay, B}, title = {Factors associated with uptake of post-abortion family planning in Shire town, Tigray, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {928}, doi = {10.1186/s13104-018-4029-7}, pmid = {30591074}, issn = {1756-0500}, abstract = {OBJECTIVES: Post-abortion contraceptive service is pivotal for the prevention of unwanted pregnancy and alleviation of its complication. Worldwide half of the pregnancy is unplanned, whereas unwanted pregnancy ends up with abortion. This study assessed post-abortion contraceptive uptake and associated factors among abortion service users at health institution in Shire town, North Ethiopia. Institutional based cross-sectional study was conducted from December 15/2016 to March 15, 2017, in Shire town. Data were collected using systematic random sampling technique. Bivariate and multivariable analyses were done to determine the association of each independent variable with the dependent variable.

RESULTS: Overall post-abortion contraceptive utilization in this study was 61.5%. Married [AOR 2.59, 95% CI (1.16, 5.65)], completed College education [AOR 5.69, 95% CI (1.61, 20.11)], previous contraceptive used [AOR 3.62, 95% CI (1.77, 7.40)], counseling of family planning [AOR 3.53 95% CI (1.69, 7.37)], grand multipara [AOR 7.91, 95% CI (1.66, 37.74)] and public health institution [AOR 5.95, 95% CI (3.03, 11.72)] were significantly associated with the post-abortion contraceptive utilization. In this study, post-abortion contraceptive utilization was about two-third. Being married, had been completing a college education, had been receiving family planning counseling, previous contraceptive usage, abortion care service at public health institution, and being grand multiparty were determinants of post-abortion contraceptive utilization.}, } @article {pmid30591051, year = {2018}, author = {Song, M and Finley, SD}, title = {Mechanistic insight into activation of MAPK signaling by pro-angiogenic factors.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {145}, doi = {10.1186/s12918-018-0668-5}, pmid = {30591051}, issn = {1752-0509}, support = {1552065//National Science Foundation/ ; }, abstract = {BACKGROUND: Angiogenesis is important in physiological and pathological conditions, as blood vessels provide nutrients and oxygen needed for tissue growth and survival. Therefore, targeting angiogenesis is a prominent strategy in both tissue engineering and cancer treatment. However, not all of the approaches to promote or inhibit angiogenesis lead to successful outcomes. Angiogenesis-based therapies primarily target pro-angiogenic factors such as vascular endothelial growth factor-A (VEGF) or fibroblast growth factor (FGF) in isolation. However, pre-clinical and clinical evidence shows these therapies often have limited effects. To improve therapeutic strategies, including targeting FGF and VEGF in combination, we need a quantitative understanding of the how the promoters combine to stimulate angiogenesis.

RESULTS: In this study, we trained and validated a detailed mathematical model to quantitatively characterize the crosstalk of FGF and VEGF intracellular signaling. This signaling is initiated by FGF binding to the FGF receptor 1 (FGFR1) and heparan sulfate glycosaminoglycans (HSGAGs) or VEGF binding to VEGF receptor 2 (VEGFR2) to promote downstream signaling. The model focuses on FGF- and VEGF-induced mitogen-activated protein kinase (MAPK) signaling and phosphorylation of extracellular regulated kinase (ERK), which promotes cell proliferation. We apply the model to predict the dynamics of phosphorylated ERK (pERK) in response to the stimulation by FGF and VEGF individually and in combination. The model predicts that FGF and VEGF have differential effects on pERK. Additionally, since VEGFR2 upregulation has been observed in pathological conditions, we apply the model to investigate the effects of VEGFR2 density and trafficking parameters. The model predictions show that these parameters significantly influence the response to VEGF stimulation.

CONCLUSIONS: The model agrees with experimental data and is a framework to synthesize and quantitatively explain experimental studies. Ultimately, the model provides mechanistic insight into FGF and VEGF interactions needed to identify potential targets for pro- or anti-angiogenic therapies.}, } @article {pmid30591037, year = {2018}, author = {Zeng, Z and Espino, S and Roy, A and Li, X and Khan, SA and Clare, SE and Jiang, X and Neapolitan, R and Luo, Y}, title = {Using natural language processing and machine learning to identify breast cancer local recurrence.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {498}, doi = {10.1186/s12859-018-2466-x}, pmid = {30591037}, issn = {1471-2105}, support = {R01 LM011663/LM/NLM NIH HHS/United States ; R01 LM011962/LM/NLM NIH HHS/United States ; R21 LM012618/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Identifying local recurrences in breast cancer from patient data sets is important for clinical research and practice. Developing a model using natural language processing and machine learning to identify local recurrences in breast cancer patients can reduce the time-consuming work of a manual chart review.

METHODS: We design a novel concept-based filter and a prediction model to detect local recurrences using EHRs. In the training dataset, we manually review a development corpus of 50 progress notes and extract partial sentences that indicate breast cancer local recurrence. We process these partial sentences to obtain a set of Unified Medical Language System (UMLS) concepts using MetaMap, and we call it positive concept set. We apply MetaMap on patients' progress notes and retain only the concepts that fall within the positive concept set. These features combined with the number of pathology reports recorded for each patient are used to train a support vector machine to identify local recurrences.

RESULTS: We compared our model with three baseline classifiers using either full MetaMap concepts, filtered MetaMap concepts, or bag of words. Our model achieved the best AUC (0.93 in cross-validation, 0.87 in held-out testing).

CONCLUSIONS: Compared to a labor-intensive chart review, our model provides an automated way to identify breast cancer local recurrences. We expect that by minimally adapting the positive concept set, this study has the potential to be replicated at other institutions with a moderately sized training dataset.}, } @article {pmid30591036, year = {2018}, author = {Dey, S and Luo, H and Fokoue, A and Hu, J and Zhang, P}, title = {Predicting adverse drug reactions through interpretable deep learning framework.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 21}, pages = {476}, doi = {10.1186/s12859-018-2544-0}, pmid = {30591036}, issn = {1471-2105}, abstract = {BACKGROUND: Adverse drug reactions (ADRs) are unintended and harmful reactions caused by normal uses of drugs. Predicting and preventing ADRs in the early stage of the drug development pipeline can help to enhance drug safety and reduce financial costs.

METHODS: In this paper, we developed machine learning models including a deep learning framework which can simultaneously predict ADRs and identify the molecular substructures associated with those ADRs without defining the substructures a-priori.

RESULTS: We evaluated the performance of our model with ten different state-of-the-art fingerprint models and found that neural fingerprints from the deep learning model outperformed all other methods in predicting ADRs. Via feature analysis on drug structures, we identified important molecular substructures that are associated with specific ADRs and assessed their associations via statistical analysis.

CONCLUSIONS: The deep learning model with feature analysis, substructure identification, and statistical assessment provides a promising solution for identifying risky components within molecular structures and can potentially help to improve drug safety evaluation.}, } @article {pmid30591035, year = {2018}, author = {Li, Z and He, B and Kou, Q and Wang, Z and Wu, S and Liu, Y and Feng, W and Liu, X}, title = {Evaluation of top-down mass spectral identification with homologous protein sequences.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {494}, doi = {10.1186/s12859-018-2462-1}, pmid = {30591035}, issn = {1471-2105}, support = {R01 GM118470/GM/NIGMS NIH HHS/United States ; R01 GM125991/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Top-down mass spectrometry has unique advantages in identifying proteoforms with multiple post-translational modifications and/or unknown alterations. Most software tools in this area search top-down mass spectra against a protein sequence database for proteoform identification. When the species studied in a mass spectrometry experiment lacks its proteome sequence database, a homologous protein sequence database can be used for proteoform identification. The accuracy of homologous protein sequences affects the sensitivity of proteoform identification and the accuracy of mass shift localization.

RESULTS: We tested TopPIC, a commonly used software tool for top-down mass spectral identification, on a top-down mass spectrometry data set of Escherichia coli K12 MG1655, and evaluated its performance using an Escherichia coli K12 MG1655 proteome database and a homologous protein database. The number of identified spectra with the homologous database was about half of that with the Escherichia coli K12 MG1655 database. We also tested TopPIC on a top-down mass spectrometry data set of human MCF-7 cells and obtained similar results.

CONCLUSIONS: Experimental results demonstrated that TopPIC is capable of identifying many proteoform spectrum matches and localizing unknown alterations using homologous protein sequences containing no more than 2 mutations.}, } @article {pmid30591034, year = {2018}, author = {Zhang, Y and Liu, X and MacLeod, J and Liu, J}, title = {Discerning novel splice junctions derived from RNA-seq alignment: a deep learning approach.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {971}, doi = {10.1186/s12864-018-5350-1}, pmid = {30591034}, issn = {1471-2164}, support = {1054631//National Science Foundation/ ; P30CA177558//National Institutes of Health/ ; P30 CA177558/CA/NCI NIH HHS/United States ; R01 HG006272/HG/NHGRI NIH HHS/United States ; 5R01HG006272-03//National Institutes of Health/ ; }, abstract = {BACKGROUND: Exon splicing is a regulated cellular process in the transcription of protein-coding genes. Technological advancements and cost reductions in RNA sequencing have made quantitative and qualitative assessments of the transcriptome both possible and widely available. RNA-seq provides unprecedented resolution to identify gene structures and resolve the diversity of splicing variants. However, currently available ab initio aligners are vulnerable to spurious alignments due to random sequence matches and sample-reference genome discordance. As a consequence, a significant set of false positive exon junction predictions would be introduced, which will further confuse downstream analyses of splice variant discovery and abundance estimation.

RESULTS: In this work, we present a deep learning based splice junction sequence classifier, named DeepSplice, which employs convolutional neural networks to classify candidate splice junctions. We show (I) DeepSplice outperforms state-of-the-art methods for splice site classification when applied to the popular benchmark dataset HS3D, (II) DeepSplice shows high accuracy for splice junction classification with GENCODE annotation, and (III) the application of DeepSplice to classify putative splice junctions generated by Rail-RNA alignment of 21,504 human RNA-seq data significantly reduces 43 million candidates into around 3 million highly confident novel splice junctions.

CONCLUSIONS: A model inferred from the sequences of annotated exon junctions that can then classify splice junctions derived from primary RNA-seq data has been implemented. The performance of the model was evaluated and compared through comprehensive benchmarking and testing, indicating a reliable performance and gross usability for classifying novel splice junctions derived from RNA-seq alignment.}, } @article {pmid30591030, year = {2018}, author = {Khan, A and Liu, Q and Wang, K}, title = {iMEGES: integrated mental-disorder GEnome score by deep neural network for prioritizing the susceptibility genes for mental disorders in personal genomes.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {501}, doi = {10.1186/s12859-018-2469-7}, pmid = {30591030}, issn = {1471-2105}, support = {P50 MH096891/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R01 MH105472/MH/NIMH NIH HHS/United States ; R01 MH108728/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; P50 MH084053/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; P01 AG002219/AG/NIA NIH HHS/United States ; R01 MH093725/MH/NIMH NIH HHS/United States ; P50 AG005138/AG/NIA NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; HHSN271201300031C/MH/NIMH NIH HHS/United States ; R01 MH080405/MH/NIMH NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; R01 HG006465/HG/NHGRI NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: A range of rare and common genetic variants have been discovered to be potentially associated with mental diseases, but many more have not been uncovered. Powerful integrative methods are needed to systematically prioritize both variants and genes that confer susceptibility to mental diseases in personal genomes of individual patients and to facilitate the development of personalized treatment or therapeutic approaches.

METHODS: Leveraging deep neural network on the TensorFlow framework, we developed a computational tool, integrated Mental-disorder GEnome Score (iMEGES), for analyzing whole genome/exome sequencing data on personal genomes. iMEGES takes as input genetic mutations and phenotypic information from a patient with mental disorders, and outputs the rank of whole genome susceptibility variants and the prioritized disease-specific genes for mental disorders by integrating contributions from coding and non-coding variants, structural variants (SVs), known brain expression quantitative trait loci (eQTLs), and epigenetic information from PsychENCODE.

RESULTS: iMEGES was evaluated on multiple datasets of mental disorders, and it achieved improved performance than competing approaches when large training dataset is available.

CONCLUSION: iMEGES can be used in population studies to help the prioritization of novel genes or variants that might be associated with the susceptibility to mental disorders, and also on individual patients to help the identification of genes or variants related to mental diseases.}, } @article {pmid30591027, year = {2018}, author = {Zheng, C and Xu, R}, title = {Large-scale mining disease comorbidity relationships from post-market drug adverse events surveillance data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {500}, doi = {10.1186/s12859-018-2468-8}, pmid = {30591027}, issn = {1471-2105}, support = {R01 AG057557/AG/NIA NIH HHS/United States ; UL1 TR002548/TR/NCATS NIH HHS/United States ; DP2 HD084068/HD/NICHD NIH HHS/United States ; R56 AG062272/AG/NIA NIH HHS/United States ; R01 AG061388/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: Systems approaches in studying disease relationship have wide applications in biomedical discovery, such as disease mechanism understanding and drug discovery. The FDA Adverse Event Reporting System (FAERS) contains rich information about patient diseases, medications, drug adverse events and demographics of 17 million case reports. Here, we explored this data resource to mine disease comorbidity relationships using association rule mining algorithm and constructed a disease comorbidity network.

RESULTS: We constructed a disease comorbidity network with 1059 disease nodes and 12,608 edges using association rule mining of FAERS (14,157 rules). We evaluated the performance of comorbidity mining from FAERS using known disease comorbidities of multiple sclerosis (MS), psoriasis and obesity that represent rare, moderate and common disease respectively. Comorbidities of MS, obesity and psoriasis obtained from our network achieved precisions of 58.6%, 73.7%, 56.2% and recalls 87.5%, 69.2% and 72.7% separately. We performed comparative analysis of the disease comorbidity network with disease semantic network, disease genetic network and disease treatment network. We showed that (1) disease comorbidity clusters exhibit significantly higher semantic similarity than random network (0.18 vs 0.10); (2) disease comorbidity clusters share significantly more genes (0.46 vs 0.06); and (3) disease comorbidity clusters share significantly more drugs (0.64 vs 0.17). Finally, we demonstrated that the disease comorbidity network has potential in uncovering novel disease relationships using asthma as a case study.

CONCLUSIONS: Our study presented the first comprehensive attempt to build a disease comorbidity network from FDA Adverse Event Reporting System. This network shows well correlated with disease semantic similarity, disease genetics and disease treatment, which has great potential in disease genetics prediction and drug discovery.}, } @article {pmid30591025, year = {2018}, author = {Gao, Y and Jiang, J and Yang, S and Cao, J and Han, B and Wang, Y and Zhang, Y and Yu, Y and Zhang, S and Zhang, Q and Fang, L and Cantrell, B and Sun, D}, title = {Genome-wide association study of Mycobacterium avium subspecies Paratuberculosis infection in Chinese Holstein.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {972}, doi = {10.1186/s12864-018-5385-3}, pmid = {30591025}, issn = {1471-2164}, support = {31472065//National Natural Science Foundation of China/ ; 31872330//National Natural Science Foundation of China/ ; BAIC06-2016//Beijing Dairy Industry Innovation Team/ ; BAIC06-2017//Beijing Dairy Industry Innovation Team/ ; 6152013//Beijing Natural Science Foundation/ ; CARS-36//earmarked fund for Modern Agro-industry Technology Research System/ ; IRT1191//the Program for Changjiang Scholar and Innovation Research Team in University/ ; }, abstract = {BACKGROUND: Paratuberculosis is a contagious, chronic and enteric disease in ruminants, which is caused by Mycobacterium avium subspecies paratuberculosis (MAP) infection, resulting in enormous economic losses worldwide. There is currently no effective cure for MAP infection or a vaccine, it is thus important to explore the genetic variants that contribute to host susceptibility to infection by MAP, which may provide a better understanding of the mechanisms of paratuberculosis and benefit animal genetic improvement. Herein we performed a genome-wide association study (GWAS) to identify genomic regions and candidate genes associated with susceptibility to MAP infection in dairy cattle.

RESULTS: Using Illumina Bovine 50 K (54,609 SNPs) and GeneSeek HD (138,893 SNPs) chips, two analytical approaches were performed, GRAMMAR-GC and ROADTRIPS in 937 Chinese Holstein cows, among which individuals genotyped by the 50 K chip were imputed to HD SNPs with Beagle software. Consequently, 15 and 11 significant SNPs (P < 5 × 10- 5) were identified with GRAMMAR-GC and ROADTDRIPS, respectively. A total of 10 functional genes were in proximity to (i.e., within 1 Mb) these SNPs, including IL4, IL5, IL13, IRF1, MyD88, PACSIN1, DEF6, TDP2, ZAP70 and CSF2. Functional enrichment analysis showed that these genes were involved in immune related pathways, such as interleukin, T cell receptor signaling pathways and inflammatory bowel disease (IBD), implying their potential associations with susceptibility to MAP infection. In addition, by examining the publicly available cattle QTLdb, a previous QTL for MAP was found to be overlapped with one of regions detected currently at 32.5 Mb on BTA23, where the TDP2 gene was anchored.

CONCLUSIONS: In conclusion, we identified 26 SNPs located on 15 chromosomes in the Chinese Holstein population using two GWAS strategies with high density SNPs. Integrated analysis of GWAS, biological functions and the reported QTL information helps to detect positional candidate genes and the identification of regions associated with susceptibility to MAP traits in dairy cattle.}, } @article {pmid30591023, year = {2018}, author = {Dhruba, SR and Rahman, R and Matlock, K and Ghosh, S and Pal, R}, title = {Application of transfer learning for cancer drug sensitivity prediction.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {497}, doi = {10.1186/s12859-018-2465-y}, pmid = {30591023}, issn = {1471-2105}, support = {R01 GM122084/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: In precision medicine, scarcity of suitable biological data often hinders the design of an appropriate predictive model. In this regard, large scale pharmacogenomics studies, like CCLE and GDSC hold the promise to mitigate the issue. However, one cannot directly employ data from multiple sources together due to the existing distribution shift in data. One way to solve this problem is to utilize the transfer learning methodologies tailored to fit in this specific context.

RESULTS: In this paper, we present two novel approaches for incorporating information from a secondary database for improving the prediction in a target database. The first approach is based on latent variable cost optimization and the second approach considers polynomial mapping between the two databases. Utilizing CCLE and GDSC databases, we illustrate that the proposed approaches accomplish a better prediction of drug sensitivities for different scenarios as compared to the existing approaches.

CONCLUSION: We have compared the performance of the proposed predictive models with database-specific individual models as well as existing transfer learning approaches. We note that our proposed approaches exhibit superior performance compared to the abovementioned alternative techniques for predicting sensitivity for different anti-cancer compounds, particularly the nonlinear mapping model shows the best overall performance.}, } @article {pmid30591021, year = {2018}, author = {Jenkins, SV and Vang, KB and Gies, A and Griffin, RJ and Jun, SR and Nookaew, I and Dings, RPM}, title = {Sample storage conditions induce post-collection biases in microbiome profiles.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {227}, doi = {10.1186/s12866-018-1359-5}, pmid = {30591021}, issn = {1471-2180}, support = {P20 GM103625/GM/NIGMS NIH HHS/United States ; P20 GM125503/GM/NIGMS NIH HHS/United States ; P20GM103625//National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: Here we investigated the influence of different stabilization and storage strategies on the quality and composition of the fecal microbial community. Namely, same-day isolated murine DNA was compared to samples stored for 1 month in air at ambient temperature, with or without preservative buffers (i.e. EDTA and lysis buffer), different temperatures (i.e. 4 °C, - 20 °C, and - 80 °C), and hypoxic conditions.

RESULTS: Only storage in lysis buffer significantly reduced DNA content, yet without integrity loss. Storage in EDTA affected alpha diversity the most, which was also reflected in cluster separation. Distinct changes were also seen in the phyla and bacterial species abundance per storage strategy. Metabolic function analysis showed 22 pathways not significantly affected by storage conditions, whereas the tyrosine metabolism pathway was significantly changed in all strategies except by EDTA.

CONCLUSION: Each long-term storage strategy introduced a unique post-collection bias, which is important to take into account when interpreting data.}, } @article {pmid30591019, year = {2018}, author = {Vihinen, M}, title = {Systematics for types and effects of DNA variations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {974}, doi = {10.1186/s12864-018-5262-0}, pmid = {30591019}, issn = {1471-2164}, support = {VR 2015-02510//Vetenskapsrådet/ ; }, abstract = {BACKGROUND: Numerous different types of variations can occur in DNA and have diverse effects and consequences. The Variation Ontology (VariO) was developed for systematic descriptions of variations and their effects at DNA, RNA and protein levels.

RESULTS: VariO use and terms for DNA variations are described in depth. VariO provides systematic names for variation types and detailed descriptions for changes in DNA function, structure and properties. The principles of VariO are presented along with examples from published articles or databases, most often in relation to human diseases. VariO terms describe local DNA changes, chromosome number and structure variants, chromatin alterations, as well as genomic changes, whether of genetic or non-genetic origin.

CONCLUSIONS: DNA variation systematics facilitates unambiguous descriptions of variations and their effects and further reuse and integration of data from different sources by both human and computers.}, } @article {pmid30591015, year = {2018}, author = {Chowdhury, S and Dong, X and Qian, L and Li, X and Guan, Y and Yang, J and Yu, Q}, title = {A multitask bi-directional RNN model for named entity recognition on Chinese electronic medical records.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {499}, doi = {10.1186/s12859-018-2467-9}, pmid = {30591015}, issn = {1471-2105}, abstract = {BACKGROUND: Electronic Medical Record (EMR) comprises patients' medical information gathered by medical stuff for providing better health care. Named Entity Recognition (NER) is a sub-field of information extraction aimed at identifying specific entity terms such as disease, test, symptom, genes etc. NER can be a relief for healthcare providers and medical specialists to extract useful information automatically and avoid unnecessary and unrelated information in EMR. However, limited resources of available EMR pose a great challenge for mining entity terms. Therefore, a multitask bi-directional RNN model is proposed here as a potential solution of data augmentation to enhance NER performance with limited data.

METHODS: A multitask bi-directional RNN model is proposed for extracting entity terms from Chinese EMR. The proposed model can be divided into a shared layer and a task specific layer. Firstly, vector representation of each word is obtained as a concatenation of word embedding and character embedding. Then Bi-directional RNN is used to extract context information from sentence. After that, all these layers are shared by two different task layers, namely the parts-of-speech tagging task layer and the named entity recognition task layer. These two tasks layers are trained alternatively so that the knowledge learned from named entity recognition task can be enhanced by the knowledge gained from parts-of-speech tagging task.

RESULTS: The performance of our proposed model has been evaluated in terms of micro average F-score, macro average F-score and accuracy. It is observed that the proposed model outperforms the baseline model in all cases. For instance, experimental results conducted on the discharge summaries show that the micro average F-score and the macro average F-score are improved by 2.41% point and 4.16% point, respectively, and the overall accuracy is improved by 5.66% point.

CONCLUSIONS: In this paper, a novel multitask bi-directional RNN model is proposed for improving the performance of named entity recognition in EMR. Evaluation results using real datasets demonstrate the effectiveness of the proposed model.}, } @article {pmid30591014, year = {2018}, author = {Hoeksema, M and Jonker, MJ and Bel, K and Brul, S and Ter Kuile, BH}, title = {Genome rearrangements in Escherichia coli during de novo acquisition of resistance to a single antibiotic or two antibiotics successively.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {973}, doi = {10.1186/s12864-018-5353-y}, pmid = {30591014}, issn = {1471-2164}, abstract = {BACKGROUND: The ability of bacteria to acquire resistance to antibiotics relies to a large extent on their capacity for genome modification. Prokaryotic genomes are highly plastic and can utilize horizontal gene transfer, point mutations, and gene deletions or amplifications to realize genome expansion and rearrangements. The contribution of point mutations to de novo acquisition of antibiotic resistance is well-established. In this study, the internal genome rearrangement of Escherichia coli during to de novo acquisition of antibiotic resistance was investigated using whole-genome sequencing.

RESULTS: Cells were made resistant to one of the four antibiotics and subsequently to one of the three remaining. This way the initial genetic rearrangements could be documented together with the effects of an altered genetic background on subsequent development of resistance. A DNA fragment including ampC was amplified by a factor sometimes exceeding 100 as a result of exposure to amoxicillin. Excision of prophage e14 was observed in many samples with a double exposure history, but not in cells exposed to a single antibiotic, indicating that the activation of the SOS stress response alone, normally the trigger for excision, was not sufficient to cause excision of prophage e14. Partial deletion of clpS and clpA occurred in strains exposed to enrofloxacin and tetracycline. Other deletions were observed in some strains, but not in replicates with the exact same exposure history. Various insertion sequence transpositions correlated with exposure to specific antibiotics.

CONCLUSIONS: Many of the genome rearrangements have not been reported before to occur during resistance development. The observed correlation between genome rearrangements and specific antibiotic pressure, as well as their presence in independent replicates indicates that these events do not occur randomly. Taken together, the observed genome rearrangements illustrate the plasticity of the E. coli genome when exposed to antibiotic stress.}, } @article {pmid30591012, year = {2018}, author = {Liu, X and Xie, L and Wu, Z and Wang, K and Zhao, Z and Ruan, J and Zhi, D}, title = {The International Conference on Intelligent Biology and Medicine (ICIBM) 2018: bioinformatics towards translational applications.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {492}, doi = {10.1186/s12859-018-2460-3}, pmid = {30591012}, issn = {1471-2105}, abstract = {The 2018 International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held on June 10-12, 2018, in Los Angeles, California, USA. The conference consisted of a total of eleven scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks, which covered a wild range of aspects of bioinformatics, medical informatics, systems biology and intelligent computing. Here, we summarize nine research articles selected for publishing in BMC Bioinformatics.}, } @article {pmid30591011, year = {2018}, author = {He, Y and Ji, J and Xie, L and Zhang, X and Xue, F}, title = {A new insight into underlying disease mechanism through semi-parametric latent differential network model.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {493}, doi = {10.1186/s12859-018-2461-2}, pmid = {30591011}, issn = {1471-2105}, abstract = {BACKGROUND: In genomic studies, to investigate how the structure of a genetic network differs between two experiment conditions is a very interesting but challenging problem, especially in high-dimensional setting. Existing literatures mostly focus on differential network modelling for continuous data. However, in real application, we may encounter discrete data or mixed data, which urges us to propose a unified differential network modelling for various data types.

RESULTS: We propose a unified latent Gaussian copula differential network model which provides deeper understanding of the unknown mechanism than that among the observed variables. Adaptive rank-based estimation approaches are proposed with the assumption that the true differential network is sparse. The adaptive estimation approaches do not require precision matrices to be sparse, and thus can allow the individual networks to contain hub nodes. Theoretical analysis shows that the proposed methods achieve the same parametric convergence rate for both the difference of the precision matrices estimation and differential structure recovery, which means that the extra modeling flexibility comes at almost no cost of statistical efficiency. Besides theoretical analysis, thorough numerical simulations are conducted to compare the empirical performance of the proposed methods with some other state-of-the-art methods. The result shows that the proposed methods work quite well for various data types. The proposed method is then applied on gene expression data associated with lung cancer to illustrate its empirical usefulness.

CONCLUSIONS: The proposed latent variable differential network models allows for various data-types and thus are more flexible, which also provide deeper understanding of the unknown mechanism than that among the observed variables. Theoretical analysis, numerical simulation and real application all demonstrate the great advantages of the latent differential network modelling and thus are highly recommended.}, } @article {pmid30591010, year = {2018}, author = {Shen, J and Vasaikar, S and Zhang, B}, title = {DLAD4U: deriving and prioritizing disease lists from PubMed literature.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {495}, doi = {10.1186/s12859-018-2463-0}, pmid = {30591010}, issn = {1471-2105}, abstract = {BACKGROUND: Due to recent technology advancements, disease related knowledge is growing rapidly. It becomes nontrivial to go through all published literature to identify associations between human diseases and genetic, environmental, and life style factors, disease symptoms, and treatment strategies. Here we report DLAD4U (Disease List Automatically Derived For You), an efficient, accurate and easy-to-use disease search engine based on PubMed literature.

RESULTS: DLAD4U uses the eSearch and eFetch APIs from the National Center for Biotechnology Information (NCBI) to find publications related to a query and to identify diseases from the retrieved publications. The hypergeometric test was used to prioritize identified diseases for displaying to users. DLAD4U accepts any valid queries for PubMed, and the output results include a ranked disease list, information associated with each disease, chronologically-ordered supporting publications, a summary of the run, and links for file export. DLAD4U outperformed other disease search engines in our comparative evaluation using selected genes and drugs as query terms and manually curated data as "gold standard". For 100 genes that are associated with only one disease in the gold standard, the Mean Average Precision (MAP) measure from DLAD4U was 0.77, which clearly outperformed other tools. For 10 genes that are associated with multiple diseases in the gold standard, the mean precision, recall and F-measure scores from DLAD4U were always higher than those from other tools. The superior performance of DLAD4U was further confirmed using 100 drugs as queries, with an MAP of 0.90.

CONCLUSIONS: DLAD4U is a new, intuitive disease search engine that takes advantage of existing resources at NCBI to provide computational efficiency and uses statistical analyses to ensure accuracy. DLAD4U is publicly available at http://dlad4u.zhang-lab.org .}, } @article {pmid30591009, year = {2018}, author = {Liu, T and Wang, Z}, title = {Reconstructing high-resolution chromosome three-dimensional structures by Hi-C complex networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 17}, pages = {496}, doi = {10.1186/s12859-018-2464-z}, pmid = {30591009}, issn = {1471-2105}, support = {R15 GM120650/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Hi-C data have been widely used to reconstruct chromosomal three-dimensional (3D) structures. One of the key limitations of Hi-C is the unclear relationship between spatial distance and the number of Hi-C contacts. Many methods used a fixed parameter when converting the number of Hi-C contacts to wish distances. However, a single parameter cannot properly explain the relationship between wish distances and genomic distances or the locations of topologically associating domains (TADs).

RESULTS: We have addressed one of the key issues of using Hi-C data, that is, the unclear relationship between spatial distances and the number of Hi-C contacts, which is crucial to understand significant biological functions, such as the enhancer-promoter interactions. Specifically, we developed a new method to infer this converting parameter and pairwise Euclidean distances based on the topology of the Hi-C complex network (HiCNet). The inferred distances were modeled by clustering coefficient and multiple other types of constraints. We found that our inferred distances between bead-pairs within the same TAD were apparently smaller than those distances between bead-pairs from different TADs. Our inferred distances had a higher correlation with fluorescence in situ hybridization (FISH) data, fitted the localization patterns of Xist transcripts on DNA, and better matched 156 pairs of protein-enabled long-range chromatin interactions detected by ChIA-PET. Using the inferred distances and another round of optimization, we further reconstructed 40 kb high-resolution 3D chromosomal structures of mouse male ES cells. The high-resolution structures successfully illustrate TADs and DNA loops (peaks in Hi-C contact heatmaps) that usually indicate enhancer-promoter interactions.

CONCLUSIONS: We developed a novel method to infer the wish distances between DNA bead-pairs from Hi-C contacts. High-resolution 3D structures of chromosomes were built based on the newly-inferred wish distances. This whole process has been implemented as a tool named HiCNet, which is publicly available at http://dna.cs.miami.edu/HiCNet/ .}, } @article {pmid30590692, year = {2018}, author = {Rousselle, M and Laverré, A and Figuet, E and Nabholz, B and Galtier, N}, title = {Influence of recombination and GC-biased gene conversion on the adaptive and non-adaptive substitution rate in mammals vs. birds.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy243}, pmid = {30590692}, issn = {1537-1719}, abstract = {Recombination is expected to affect functional sequence evolution in several ways. On the one hand, recombination is thought to improve the efficiency of multi-locus selection by dissipating linkage disequilibrium. On the other hand, natural selection can be counteracted by recombination-associated transmission distorters such as GC-biased gene conversion (gBGC), which tends to promote G and C alleles irrespective of their fitness effect in high-recombining regions. It has been suggested that gBGC might impact coding sequence evolution in vertebrates, and particularly the ratio of non-synonymous to synonymous substitution rates (dN/dS). However, distinctive gBGC patterns have been reported in mammals and birds, maybe reflecting the documented contrasts in evolutionary dynamics of recombination rate between these two taxa. Here, we explore how recombination and gBGC affect coding sequence evolution in mammals and birds by analyzing proteome-wide data in six species of Galloanserae (fowls) and six species of catarrhine primates. We estimated the dN/dS ratio and rates of adaptive and non-adaptive evolution in bins of genes of increasing recombination rate, separately analyzing AT→GC, GC→AT and G↔C/A↔T mutations. We show that in both taxa, recombination and gBGC entail a decrease in dN/dS. Our analysis indicates that recombination enhances the efficiency of purifying selection by lowering Hill-Robertson effects, while gBGC leads to an overestimation of the adaptive rate of AT→GC mutations. Finally, we report a mutagenic effect of recombination, which is independent of gBGC.}, } @article {pmid30590689, year = {2018}, author = {Liu, DW and Wang, FY and Lin, JJ and Thompson, A and Lu, Y and Vo, D and Yan, HY and Zakon, H}, title = {The cone opsin repertoire of osteoglossomorph fishes: gene loss in mormyrid electric fish and a long wave-length sensitive cone opsin that survived 3R.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy241}, pmid = {30590689}, issn = {1537-1719}, abstract = {Vertebrates have four classes of cone opsin genes derived from two rounds of genome duplication. These are short wavelength sensitive 1 (SWS1), short wavelength-sensitive 2 (SWS2), medium wavelength-sensitive (RH2), and long wavelength-sensitive (LWS). Teleosts had another genome duplication at their origin and it is believed that only one of each cone opsin survived the ancestral teleost duplication event. We tested this by examining the retinal cones of a basal teleost group, the osteoglossomorphs. Surprisingly, this lineage has lost the typical vertebrate green-sensitive RH2 opsin gene and, instead, has a duplicate of the LWS opsin that is green-sensitive. This parallels the situation in mammalian evolution in which the RH2 opsin gene was lost in basal mammals and a green-sensitive opsin re-evolved in Old World, and independently in some New World, primates from an LWS opsin gene. Another group of fish, the characins, possess green-sensitive LWS cones. Phylogenetic analysis shows that the evolution of green-sensitive LWS opsins in these two teleost groups derives from a common ancestral LWS opsin that acquired green-sensitivity. Additionally, the nocturnally-active African weakly electric fish (Mormyroideae), which are osteoglossomorphs, show a loss of the SWS1 opsin gene. In comparison with the independently evolved nocturnally-active South American weakly electric fish (Gymnotiformes) with a functionally monochromatic LWS opsin cone retina, the presence of SWS2, LWS, and LWS2 cone opsins in mormyrids suggests the possibility of color vision.}, } @article {pmid30590616, year = {2018}, author = {Echave, J}, title = {Beyond stability constraints: a biophysical model of enzyme evolution with selection on stability and activity.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy244}, pmid = {30590616}, issn = {1537-1719}, abstract = {The rate of evolution varies among sites within proteins. In enzymes, two rate gradients are observed: rate decreases with increasing local packing and it increases with increasing distance from catalytic residues. The rate-packing gradient would be mainly due to stability constraints and is well reproduced by biophysical models with selection for protein stability. However, stability constraints are unlikely to account for the rate-distance gradient. Here, to explore the mechanistic underpinnings of the rate gradients observed in enzymes, I propose a stability-activity model of enzyme evolution, Msa. This model is based on a two-dimensional fitness function that depends on stability, quantified by ΔG, the enzyme's folding free energy, and activity, quantified by ΔG*, the activation energy barrier of the enzymatic reaction. I test Msa on a diverse dataset of enzymes, comparing it with two simpler models: Ms, which depends only on ΔG, and Ma, which depends only on ΔG*. I found that Msa clearly outperforms both Ms and Ma and it accounts for both the rate-packing and rate-distance gradients. Thus, Msa captures the distribution of stability and activity constraints within enzymes, explaining the resulting patterns of rate variation among sites.}, } @article {pmid30590560, year = {2018}, author = {Haller, BC and Messer, PW}, title = {Evolutionary modeling in SLiM 3 for beginners.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy237}, pmid = {30590560}, issn = {1537-1719}, abstract = {The SLiM forward genetic simulation framework has proved to be a powerful and flexible tool for population genetic modeling. However, as a complex piece of software with many features that allow simulating a diverse assortment of evolutionary models, its initial learning curve can be difficult. Here we provide a step-by-step demonstration of how to build a simple evolutionary model in SLiM 3, to help new users get started. We will begin with a panmictic neutral model, and build up to a model of the evolution of a polygenic quantitative trait under selection for an environmental phenotypic optimum.}, } @article {pmid30590559, year = {2018}, author = {Fraïsse, C and Puixeu Sala, G and Vicoso, B}, title = {Pleiotropy modulates the efficacy of selection in Drosophila melanogaster.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy246}, pmid = {30590559}, issn = {1537-1719}, abstract = {Pleiotropy is the well-established idea that a single mutation affects multiple phenotypes. If a mutation has opposite effects on fitness when expressed in different contexts, then genetic conflict arises. Pleiotropic conflict is expected to reduce the efficacy of selection by limiting the fixation of beneficial mutations through adaptation, and the removal of deleterious mutations through purifying selection. While this has been widely discussed, in particular in the context of a putative "gender load", it has yet to be systematically quantified. In this work, we empirically estimate to which extent different pleiotropic regimes impede the efficacy of selection in Drosophila melanogaster. We use whole-genome polymorphism data from a single African population and divergence data from D. simulans to estimate the fraction of adaptive fixations (α), the rate of adaptation (ωA) and the direction of selection (DoS). After controlling for confounding covariates, we find that the different pleiotropic regimes have a relatively small, but significant, effect on selection efficacy. Specifically, our results suggest that pleiotropic sexual antagonism may restrict the efficacy of selection, but that this conflict can be resolved by limiting the expression of genes to the sex where they are beneficial. Intermediate levels of pleiotropy across tissues and life stages can also lead to maladaptation in D. melanogaster, due to inefficient purifying selection combined with low frequency of mutations that confer a selective advantage. Thus, our study highlights the need to consider the efficacy of selection in the context of antagonistic pleiotropy, and of genetic conflict in general.}, } @article {pmid30590541, year = {2018}, author = {Rafels-Ybern, À and Torres, AG and Camacho, N and Herencia-Ropero, A and Roura Frigolé, H and Wulff, TF and Raboteg, M and Bordons, A and Grau-Bove, X and Ruiz-Trillo, I and Ribas de Pouplana, L}, title = {The expansion of Inosine at the wobble position of tRNAs, and its role in the evolution of proteomes.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy245}, pmid = {30590541}, issn = {1537-1719}, abstract = {The modification of adenosine to inosine at the first position of transfer RNA (tRNA) anticodons (I34) is widespread among bacteria and eukaryotes. In bacteria, the modification is found in tRNAArg, and is catalysed by tRNA adenosine deaminase A (TadA), a homodimeric enzyme. In eukaryotes I34 is introduced in up to eight different tRNAs by the heterodimeric adenosine deaminase acting on tRNA (ADAT). This substrate expansion significantly influenced the evolution of eukaryotic genomes in terms of codon usage and tRNA gene composition. However, the selective advantages driving this process remain unclear. Here we have studied the evolution of I34, TadA, ADAT, and their relevant codons in a large set of bacterial and eukaryotic species. We show that a functional expansion of I34 to tRNAs other than tRNAArg also occurred within bacteria, in a process likely initiated by the emergence of unmodified A34-containing tRNAs. In eukaryotes, we report on a large variability in the use of I34 in protists, in contrast to a more uniform presence in fungi, plans and animals. Our data supports that the eukaryotic expansion of I34-tRNAs was driven by the improvement brought by these tRNAs to the synthesis of proteins highly enriched in certain amino acids.}, } @article {pmid30590108, year = {2018}, author = {Pinto, BJ and Colli, GR and Higham, TE and Russell, AP and Scantlebury, DP and Vitt, LJ and Gamble, T}, title = {Population genetic structure and species delimitation of a widespread, Neotropical dwarf gecko.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {54-66}, doi = {10.1016/j.ympev.2018.12.029}, pmid = {30590108}, issn = {1095-9513}, abstract = {Amazonia harbors the greatest biological diversity on Earth. One trend that spans Amazonian taxa is that most taxonomic groups either exhibit broad geographic ranges or small restricted ranges. This is likely because many traits that determine a species range size, such as dispersal ability or body size, are autocorrelated. As such, it is rare to find groups that exhibit both large and small ranges. Once identified, however, these groups provide a powerful system for isolating specific traits that influence species distributions. One group of terrestrial vertebrates, gecko lizards, tends to exhibit small geographic ranges. Despite one exception, this applies to the Neotropical dwarf geckos of the genus Gonatodes. This exception, Gonatodes humeralis, has a geographic distribution almost 1,000,000 km2 larger than the combined ranges of its 30 congeners. As the smallest member of its genus and a gecko lizard more generally, G. humeralis is an unlikely candidate to be a wide-ranged Amazonian taxon. To test whether or not G. humeralis is one or more species, we generated molecular genetic data using restriction-site associated sequencing (RADseq) and traditional Sanger methods for samples from across its range and conducted a phylogeographic study. We conclude that G. humeralis is, in fact, a single species across its contiguous range in South America. Thus, Gonatodes is a unique clade among Neotropical taxa, containing both wide-ranged and range-restricted taxa, which provides empiricists with a powerful model system to correlate complex species traits and distributions. Additionally, we provide evidence to support species-level divergence of the allopatric population from Trinidad and we resurrect the name Gonatodes ferrugineus from synonymy for this population.}, } @article {pmid30590018, year = {2018}, author = {Memar, N and Schiemann, S and Hennig, C and Findeis, D and Conradt, B and Schnabel, R}, title = {Twenty million years of evolution: The embryogenesis of four Caenorhabditis species are indistinguishable despite extensive genome divergence.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.022}, pmid = {30590018}, issn = {1095-564X}, abstract = {The four Caenorhabditis species C. elegans, C. briggsae, C. remanei and C. brenneri show more divergence at the genomic level than humans compared to mice (Stein et al., 2003; Cutter et al., 2006, 2008). However, the behavior and anatomy of these nematodes are very similar. We present a detailed analysis of the embryonic development of these species using 4D-microscopic analyses of embryos including lineage analysis, terminal differentiation patterns and bioinformatical quantifications of cell behavior. Further functional experiments support the notion that the early development of all four species depends on identical induction patterns. Based on our results, the embryonic development of all four Caenorhabditis species are nearly identical, suggesting that an apparently optimal program to construct the body plan of nematodes has been conserved for at least 20 million years. This contrasts the levels of divergence between the genomes and the protein orthologs of the Caenorhabditis species, which is comparable to the level of divergence between mouse and human. This indicates an intricate relationship between the structure of genomes and the morphology of animals.}, } @article {pmid30589978, year = {2018}, author = {García-Cortés, LA and Austerlitz, F and de Cara, MAR}, title = {An evaluation of the methods to estimate effective population size from measures of linkage disequilibrium.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13411}, pmid = {30589978}, issn = {1420-9101}, support = {AGHRUM (ANR-14-CE02-0003)//Agence Nationale de la Recherche/ ; LabEx BCDIV (ANR-10-LABX-0003-BcDiv)//Agence Nationale de la Recherche/ ; AGL-2016-75942-R//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; }, abstract = {In 1971, John Sved derived an approximate relationship between linkage disequilibrium (LD) and effective population size for an ideal finite population. This seminal work was extended by Sved and Feldman (Theor Pop Biol 4, 129, 1973) and Weir and Hill (Genetics 95, 477, 1980) who derived additional equations with the same purpose. These equations yield useful estimates of effective population size, as they require a single sample in time. As these estimates of effective population size are now commonly used on a variety of genomic data, from arrays of single nucleotide polymorphisms to whole genome data, some authors have investigated their bias through simulation studies and proposed corrections for different mating systems. However, the cause of the bias remains elusive. Here, we show the problems of using LD as a statistical measure and, analogously, the problems in estimating effective population size from such measure. For that purpose, we compare three commonly used approaches with a transition probability-based method that we develop here. It provides an exact computation of LD. We show here that the bias in the estimates of LD and effective population size are partly due to low-frequency markers, tightly linked markers or to a small total number of crossovers per generation. These biases, however, do not decrease when increasing sample size or using unlinked markers. Our results show the issues of such measures of effective population based on LD and suggest which of the method here studied should be used in empirical studies as well as the optimal distance between markers for such estimates.}, } @article {pmid30589201, year = {2018}, author = {D'Agostino, PM and Woodhouse, JN and Liew, HT and Sehnal, L and Pickford, R and Wong, HL and Burns, BP and Neilan, BA}, title = {Bioinformatic, phylogenetic and chemical analysis of the UV-absorbing compounds scytonemin and mycosporine-like amino acids from the microbial mat communities of Shark Bay, Australia.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14517}, pmid = {30589201}, issn = {1462-2920}, support = {//Australian Research Council/ ; }, abstract = {Shark Bay, Western Australia is a World Heritage area with extensive microbial mats and stromatolites. Microbial communities that comprise these mats have developed a range of mitigation strategies against changing levels of photosynthetically active and ultraviolet radiation, including the ability to biosynthesise the UV-absorbing natural products scytonemin and mycosporine-like amino acids (MAAs). To this end, the distribution of photoprotective pigments within Shark Bay microbial mats was delineated in the present study. This involved amplicon sequencing of bacterial 16S rDNA from communities at the surface and subsurface in three distinct mat types (smooth, pustular and tufted), and correlating this data with the chemical and molecular distribution of scytonemin and MAAs. Employing UV spectroscopy and MS/MS fragmentation, mycosporine-glycine, asterina and an unknown MAA were identified based on typical fragmentation patterns. Marker genes for scytonemin and MAA production (scyC and mysC) were amplified from microbial mat DNA and placed into phylogenetic context against a broad screen throughout 363 cyanobacterial genomes. Results indicate that occurrence of UV screening compounds is associated with the upper layer of Shark Bay microbial mats, and the occurrence of scytonemin is closely dependent on the abundance of cyanobacteria.}, } @article {pmid30588766, year = {2019}, author = {Shinji, J and Gotoh, H and Miyanishi, H and Lavine, MD and Lavine, LC}, title = {The activin signaling transcription factor Smox is an essential regulator of appendage size during regeneration after autotomy in the crayfish.}, journal = {Evolution & development}, volume = {21}, number = {1}, pages = {44-55}, doi = {10.1111/ede.12277}, pmid = {30588766}, issn = {1525-142X}, abstract = {Members of the phylum Arthropoda, comprising over 80% of total animal species, have evolved regenerative abilities, but little is known about the molecular mechanisms mediating this process. Transforming growth factor β (TGF-β) signaling mediates a diverse set of essential processes in animals and is a good candidate pathway for regulation of regeneration in arthropods. In this study we investigated the role of activin signaling, a TGF-β superfamily pathway, in limb regeneration in the crayfish. We identified and cloned a downstream transcription factor in the activin pathway, Smox, and characterized its function with regard to other elements of the activin signaling pathway. Gene knockdown of Smox by RNAi induced regeneration of complete but smaller pereopods after autotomy. This indicates that activin signaling via Smox functions in regulation of pereopod growth and size. The expression levels of both Smox and the activin receptor babo were closely correlated with molting. The expression level of Smox increased when babo was knocked down by RNAi, indicating that Smox and babo transcription are linked. Our study suggests that the Babo-Smox system in activin signaling is conserved in decapods, and supports an evolutionary conservation of this aspect of molecular signaling during regeneration between protostomes and deuterostomes.}, } @article {pmid30588764, year = {2019}, author = {Woyke, T and Schulz, F}, title = {Entities inside one another - a matryoshka doll in biology?.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {26-28}, doi = {10.1111/1758-2229.12716}, pmid = {30588764}, issn = {1758-2229}, support = {DE-AC02-05CH11231//U.S. Department of Energy/ ; }, } @article {pmid30588733, year = {2018}, author = {Ziomkiewicz, A and Wichary, S and Jasienska, G}, title = {Cognitive costs of reproduction: life-history trade-offs explain cognitive decline during pregnancy in women.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12494}, pmid = {30588733}, issn = {1469-185X}, support = {2012/04/M/HS6/00479//National Science Centre, Poland/ ; 2015/17/B/NZ8/02436//National Science Centre, Poland/ ; }, abstract = {Life-history theory predicts that access to limited resources leads to trade-offs between competing body functions. Women, who face higher costs of reproduction when compared to men, should be especially vulnerable to these trade-offs. We propose the 'cognitive costs of reproduction hypothesis', which states that energy trade-offs imposed by reproduction may lead to a decline in maternal cognitive function during gestation. In particular, we hypothesize that the decline in cognitive function frequently observed during pregnancy is associated with the allocation of resources between the competing energetic requirements of the mother's brain and the developing foetus. Several distinctive anatomical and physiological features including a high metabolic rate of the brain, large infant size, specific anatomical features of the placenta and trophoblast, and the lack of maternal control over glucose flow through the placenta make the occurrence of these trade-offs likely. Herein, we review several lines of evidence for trade-offs between gestation and cognition that are related to: (i) energy metabolism during reproduction; (ii) energy metabolism of the human brain; (iii) links between energy metabolism and cognitive function; and (iv) links between gestation and cognitive function. We also review evidence for the important roles of cortisol, corticotropin-releasing hormone and sex hormones in mediating the effects of gestation on cognition, and we discuss possible neurophysiological mechanisms underlying the observed effects. The evidence supports the view that energy trade-offs between foetal growth and maternal endocrine and brain function lead to changes in maternal cognition, and that this phenomenon is mediated by neuroendocrine mechanisms involving the hypothalamic-pituitary-adrenal axis, brainstem nucleus locus coeruleus and hippocampus.}, } @article {pmid30588731, year = {2018}, author = {Mathot, KJ and Dingemanse, NJ and Nakagawa, S}, title = {The covariance between metabolic rate and behaviour varies across behaviours and thermal types: meta-analytic insights.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12491}, pmid = {30588731}, issn = {1469-185X}, support = {//Max Planck Society/ ; 863.14.021//Netherlands Organisation for Scientific Research (NWO)/ ; FT130100268//Future Fellowship/ ; //Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Energy metabolism has received much attention as a potential driver of repeatable among-individual differences in behaviour (animal personality). Several factors have been hypothesized to mediate this relationship. We performed a systematic review with a meta-analysis of >70 studies comprised of >8000 individuals reporting relationships between measures of maintenance metabolic rates (i.e. basal metabolic rate, resting metabolic rate, and standard metabolic rate) and behaviour. We evaluated support for three hypothesized mediators: (i) type of behaviour, (ii) opportunities for energy re-allocation, and (iii) magnitude of energetic constraints. Relationships between measures of maintenance metabolic rate (MR) and behaviour are predicted to be strongest for behaviours with strong consequences for energy turnover (acquisition or expenditure). Consistent with this, we found that behaviours with known consequences for energy gain (e.g. foraging, dominance, boldness) or expenditure (e.g. maximum sprint speed, sustained running speed, maximum distance travelled, etc.) had strong positive correlations with MR, while behaviours with putatively weak and/or inconsistent associations with net energy gain or loss (e.g. exploration, activity, sociability) were not correlated with MR. Greater opportunities for energy reallocation are predicted to weaken relationships between MR and behaviour by creating alternative pathways to balance energy budgets. We tested this by contrasting relationships between MR and behaviour in ectotherms versus endotherms, as thermoregulation in endotherms creates additional opportunities for energy reallocation compared with ectotherms. As predicted, the relationship between behaviour and MR was stronger in ectotherms compared with endotherms. However, statistical analyses of heterogeneity among effect sizes from different species did not support energy re-allocation as the main driver of these differences. Finally, we tested whether conditions where animals face greater constraints in meeting their energy budgets (e.g. field versus laboratory, breeding versus non-breeding) increased the strength of the relationship between MR and behaviour. We found that the relationship between MR and behaviour was unaffected by either of these modifiers. This meta-analysis provides two key insights. First, we observed positive relationships of similar magnitude between MR and behaviours that bring in net energy, and behaviours that cost net energy. This result is only consistent with a performance energy-management model. Given that the studies included in our meta-analysis represent a wide range of taxa, this suggests that the performance model may be the most common model in general. Second, we found that behaviours with putatively weak or inconsistent consequences for net energy gain or expenditure (exploration, activity, sociability) show no relationship with MR. The lack of relationship between MR and behavioural traits with weak and/or inconsistent consequences for energy turnover provides the first systematic demonstration of the central importance of the ecological function of traits in mediating relationships between MR and behaviour.}, } @article {pmid30588726, year = {2018}, author = {Hill, GE and Havird, JC and Sloan, DB and Burton, RS and Greening, C and Dowling, DK}, title = {Assessing the fitness consequences of mitonuclear interactions in natural populations.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12493}, pmid = {30588726}, issn = {1469-185X}, support = {FT160100022, DP170100165, DE170100310//Australian Research Council/ ; HSF 15/2//Hermon Slade Foundation/ ; R01 GM118046//National Institutes of Health (NIH)/ ; DEB1551466//National Science Foundation (NSF)/ ; }, abstract = {Metazoans exist only with a continuous and rich supply of chemical energy from oxidative phosphorylation in mitochondria. The oxidative phosphorylation machinery that mediates energy conservation is encoded by both mitochondrial and nuclear genes, and hence the products of these two genomes must interact closely to achieve coordinated function of core respiratory processes. It follows that selection for efficient respiration will lead to selection for compatible combinations of mitochondrial and nuclear genotypes, and this should facilitate coadaptation between mitochondrial and nuclear genomes (mitonuclear coadaptation). Herein, we outline the modes by which mitochondrial and nuclear genomes may coevolve within natural populations, and we discuss the implications of mitonuclear coadaptation for diverse fields of study in the biological sciences. We identify five themes in the study of mitonuclear interactions that provide a roadmap for both ecological and biomedical studies seeking to measure the contribution of intergenomic coadaptation to the evolution of natural populations. We also explore the wider implications of the fitness consequences of mitonuclear interactions, focusing on central debates within the fields of ecology and biomedicine.}, } @article {pmid30588725, year = {2018}, author = {Kemp, PR and Griffiths, M and Polkey, MI}, title = {Muscle wasting in the presence of disease, why is it so variable?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12489}, pmid = {30588725}, issn = {1469-185X}, abstract = {Skeletal muscle wasting is a common clinical feature of many chronic diseases and also occurs in response to single acute events. The accompanying loss of strength can lead to significant disability, increased care needs and have profound negative effects on quality of life. As muscle is the most abundant source of amino acids in the body, it appears to function as a buffer for fuel and substrates that can be used to repair damage elsewhere and to feed the immune system. In essence, the fundamentals of muscle wasting are simple: less muscle is made than is broken down. However, although well-described mechanisms modulate muscle protein turnover, significant individual differences in the amount of muscle lost in the presence of a given severity of disease complicate the understanding of underlying mechanisms and suggest that individuals have different sensitivities to signals for muscle loss. Furthermore, the rate at which muscle protein is turned over under normal conditions means that clinically significant muscle loss can occur with changes in the rate of protein synthesis and/or breakdown that are too small to be measurable. Consequently, the changes in expression of factors regulating muscle turnover required to cause a decline in muscle mass are small and, except in cases of rapid wasting, there is no consistent pattern of change in the expression of factors that regulate muscle mass. MicroRNAs are fine tuners of cell phenotype and are therefore ideally suited to cause the subtle changes in proteome required to tilt the balance between synthesis and degradation in a way that causes clinically significant wasting. Herein we present a model in which muscle loss as a consequence of disease in non-muscle tissue is modulated by a set of microRNAs, the muscle expression of which is associated with severity of disease in the non-muscle tissue. These microRNAs alter fundamental biological processes including the synthesis of ribosomes and mitochondria leading to reduced protein synthesis and increased protein breakdown, thereby freeing amino acids from the muscle. We argue that the variability in muscle loss observed in the human population arises from at least two sources. The first is from pre-existing or disease-induced variation in the expression of microRNAs controlling the sensitivity of muscle to the atrophic signal and the second is from the expression of microRNAs from imprinted loci (i.e. only expressed from the maternally or paternally inherited allele) and may control the rate of myonuclear recruitment. In the absence of disease, these factors do not correlate with muscle mass, since there is no challenge to the established balance. However, in the presence of such a challenge, these microRNAs determine the rate of decline for a given disease severity. Together these mechanisms provide novel insight into the loss of muscle mass and its variation in the human population. The involvement of imprinted loci also suggests that genes that regulate early development also contribute to the ability of individuals to resist muscle loss in response to disease.}, } @article {pmid30588723, year = {2018}, author = {Hallsworth, JE}, title = {Wooden owl that redefines Earth's biosphere may yet catapult a fungus into space.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14510}, pmid = {30588723}, issn = {1462-2920}, support = {//Department of Agriculture, Environment and Rural Affairs/ ; BBF003471//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Great Britain Sasakawa Foundation/ ; //European Commission/ ; //Department of Education and Learning (DEL, Northern Ireland)/ ; }, } @article {pmid30588701, year = {2018}, author = {Sclavi, B and Herrick, J}, title = {Genome size variation and species diversity in salamanders.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13412}, pmid = {30588701}, issn = {1420-9101}, abstract = {Salamanders (Urodela) have among the largest vertebrate genomes, ranging in size from 10 to 120 pg. Although changes in genome size often occur randomly and in the absence of selection pressure, nonrandom patterns of genome size variation are evident among specific vertebrate lineages. Several reports suggest a relationship between species richness and genome size, but the exact nature of that relationship remains unclear both within and across different taxonomic groups. Here, we report (a) a negative relationship between haploid genome size (C-value) and species richness at the family taxonomic level in salamander clades; (b) a correlation of C-value and species richness with clade crown age but not with diversification rates; (c) strong associations between C-value and both geographic area and climatic-niche rate. Finally, we report a relationship between C-value diversity and species diversity at both the family- and genus-level clades in urodeles.}, } @article {pmid30587594, year = {2019}, author = {Otto, MR and René de Cotret, LP and Valverde-Chavez, DA and Tiwari, KL and Émond, N and Chaker, M and Cooke, DG and Siwick, BJ}, title = {How optical excitation controls the structure and properties of vanadium dioxide.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {450-455}, doi = {10.1073/pnas.1808414115}, pmid = {30587594}, issn = {1091-6490}, abstract = {We combine ultrafast electron diffraction and time-resolved terahertz spectroscopy measurements to link structure and electronic transport properties during the photoinduced insulator-metal transitions in vanadium dioxide. We determine the structure of the metastable monoclinic metal phase, which exhibits antiferroelectric charge order arising from a thermally activated, orbital-selective phase transition in the electron system. The relative contribution of the photoinduced monoclinic and rutile metals to the time-dependent and pump-fluence-dependent multiphase character of the film is established, as is the respective impact of these two distinct phase transitions on the observed changes in terahertz conductivity. Our results represent an important example of how light can control the properties of strongly correlated materials and demonstrate that multimodal experiments are essential when seeking a detailed connection between ultrafast changes in optical-electronic properties and lattice structure.}, } @article {pmid30587593, year = {2019}, author = {Tominaga, K and Minato, H and Murayama, T and Sasahara, A and Nishimura, T and Kiyokawa, E and Kanauchi, H and Shimizu, S and Sato, A and Nishioka, K and Tsuji, EI and Yano, M and Ogawa, T and Ishii, H and Mori, M and Akashi, K and Okamoto, K and Tanabe, M and Tada, KI and Tojo, A and Gotoh, N}, title = {Semaphorin signaling via MICAL3 induces symmetric cell division to expand breast cancer stem-like cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {625-630}, doi = {10.1073/pnas.1806851116}, pmid = {30587593}, issn = {1091-6490}, abstract = {Cancer stem-like cells (CSCs) are expanded in the CSC niche by increased frequency of symmetric cell divisions at the expense of asymmetric cell divisions. The symmetric division of CSCs is important for the malignant properties of cancer; however, underlying molecular mechanisms remain largely elusive. Here, we show a cytokine, semaphorin 3 (Sema3), produced from the CSC niche, induces symmetric divisions of CSCs to expand the CSC population. Our findings indicate that stimulation with Sema3 induced sphere formation in breast cancer cells through neuropilin 1 (NP1) receptor that was specifically expressed in breast CSCs (BCSCs). Knockdown of MICAL3, a cytoplasmic Sema3 signal transducer, greatly decreased tumor sphere formation and tumor-initiating activity. Mechanistically, Sema3 induced interaction among MICAL3, collapsin response mediator protein 2 (CRMP2), and Numb. It appears that activity of MICAL3 monooxygenase (MO) stimulated by Sema3 is required for tumor sphere formation, interaction between CRMP2 and Numb, and accumulation of Numb protein. We found that knockdown of CRMP2 or Numb significantly decreased tumor sphere formation. Moreover, MICAL3 knockdown significantly decreased Sema3-induced symmetric divisions in NP1/Numb-positive BCSCs and increased asymmetric division that produces NP1/Numb negative cells without stem-like properties. In addition, breast cancer patients with NP1-positive cancer tissues show poor prognosis. Therefore, the niche factor Sema3-stimulated NP1/MICAL3/CRMP2/Numb axis appears to expand CSCs at least partly through increased frequency of MICAL3-mediated symmetric division of CSCs.}, } @article {pmid30587592, year = {2019}, author = {Burgers, AP and Peng, LS and Muniz, JA and McClung, AC and Martin, MJ and Kimble, HJ}, title = {Clocked atom delivery to a photonic crystal waveguide.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {456-465}, doi = {10.1073/pnas.1817249115}, pmid = {30587592}, issn = {1091-6490}, abstract = {Experiments and numerical simulations are described that develop quantitative understanding of atomic motion near the surfaces of nanoscopic photonic crystal waveguides (PCWs). Ultracold atoms are delivered from a moving optical lattice into the PCW. Synchronous with the moving lattice, transmission spectra for a guided-mode probe field are recorded as functions of lattice transport time and frequency detuning of the probe beam. By way of measurements such as these, we have been able to validate quantitatively our numerical simulations, which are based upon detailed understanding of atomic trajectories that pass around and through nanoscopic regions of the PCW under the influence of optical and surface forces. The resolution for mapping atomic motion is roughly 50 nm in space and 100 ns in time. By introducing auxiliary guided-mode (GM) fields that provide spatially varying AC Stark shifts, we have, to some degree, begun to control atomic trajectories, such as to enhance the flux into the central vacuum gap of the PCW at predetermined times and with known AC Stark shifts. Applications of these capabilities include enabling high fractional filling of optical trap sites within PCWs, calibration of optical fields within PCWs, and utilization of the time-dependent, optically dense atomic medium for novel nonlinear optical experiments.}, } @article {pmid30587591, year = {2019}, author = {Pethe, MA and Rubenstein, AB and Khare, SD}, title = {Data-driven supervised learning of a viral protease specificity landscape from deep sequencing and molecular simulations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {168-176}, doi = {10.1073/pnas.1805256116}, pmid = {30587591}, issn = {1091-6490}, abstract = {Biophysical interactions between proteins and peptides are key determinants of molecular recognition specificity landscapes. However, an understanding of how molecular structure and residue-level energetics at protein-peptide interfaces shape these landscapes remains elusive. We combine information from yeast-based library screening, next-generation sequencing, and structure-based modeling in a supervised machine learning approach to report the comprehensive sequence-energetics-function mapping of the specificity landscape of the hepatitis C virus (HCV) NS3/4A protease, whose function-site-specific cleavages of the viral polyprotein-is a key determinant of viral fitness. We screened a library of substrates in which five residue positions were randomized and measured cleavability of ∼30,000 substrates (∼1% of the library) using yeast display and fluorescence-activated cell sorting followed by deep sequencing. Structure-based models of a subset of experimentally derived sequences were used in a supervised learning procedure to train a support vector machine to predict the cleavability of 3.2 million substrate variants by the HCV protease. The resulting landscape allows identification of previously unidentified HCV protease substrates, and graph-theoretic analyses reveal extensive clustering of cleavable and uncleavable motifs in sequence space. Specificity landscapes of known drug-resistant variants are similarly clustered. The described approach should enable the elucidation and redesign of specificity landscapes of a wide variety of proteases, including human-origin enzymes. Our results also suggest a possible role for residue-level energetics in shaping plateau-like functional landscapes predicted from viral quasispecies theory.}, } @article {pmid30587590, year = {2019}, author = {Santana Carrero, RM and Beceren-Braun, F and Rivas, SC and Hegde, SM and Gangadharan, A and Plote, D and Pham, G and Anthony, SM and Schluns, KS}, title = {IL-15 is a component of the inflammatory milieu in the tumor microenvironment promoting antitumor responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {599-608}, doi = {10.1073/pnas.1814642116}, pmid = {30587590}, issn = {1091-6490}, abstract = {Previous studies have provided evidence that IL-15 expression within human tumors is crucial for optimal antitumor responses; however, the regulation of IL-15 within the tumor microenvironment (TME) is unclear. We report herein, in analyses of mice implanted with various tumor cell lines, soluble IL-15/IL-15Rα complexes (sIL-15 complexes) are abundant in the interstitial fluid of tumors with expression preceding the infiltration of tumor-infiltrating lymphocytes. Moreover, IL-15 as well as type I IFN, which regulates IL-15, was required for establishing normal numbers of CD8 T cells and natural killer cells in tumors. Depending on tumor type, both the tumor and the stroma are sources of sIL-15 complexes. In analyses of IL-15 reporter mice, most myeloid cells in the TME express IL-15 with CD11b+Ly6Chi cells being the most abundant, indicating there is a large source of IL-15 protein in tumors that lies sequestered within the tumor stroma. Despite the abundance of IL-15-expressing cells, the relative levels of sIL-15 complexes are low in advanced tumors but can be up-regulated by local stimulator of IFN genes (STING) activation. Furthermore, while treatment of tumors with STING agonists leads to tumor regression, optimal STING-mediated immunity and regression of distant secondary tumors required IL-15 expression. Overall, our study reveals the dynamic regulation of IL-15 in the TME and its importance in antitumor immunity. These findings provide insight into an unappreciated attribute of the tumor landscape that contributes to antitumor immunity, which can be manipulated therapeutically to enhance antitumor responses.}, } @article {pmid30587589, year = {2019}, author = {Bocci, F and Gearhart-Serna, L and Boareto, M and Ribeiro, M and Ben-Jacob, E and Devi, GR and Levine, H and Onuchic, JN and Jolly, MK}, title = {Toward understanding cancer stem cell heterogeneity in the tumor microenvironment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {148-157}, doi = {10.1073/pnas.1815345116}, pmid = {30587589}, issn = {1091-6490}, support = {T32 ES021432/ES/NIEHS NIH HHS/United States ; }, abstract = {The epithelial-mesenchymal transition (EMT) and cancer stem cell (CSC) formation are two paramount processes driving tumor progression, therapy resistance, and cancer metastasis. Recent experiments show that cells with varying EMT and CSC phenotypes are spatially segregated in the primary tumor. The underlying mechanisms generating such spatiotemporal dynamics in the tumor microenvironment, however, remain largely unexplored. Here, we show through a mechanism-based dynamical model that the diffusion of EMT-inducing signals such as TGF-β, together with noncell autonomous control of EMT and CSC decision making via the Notch signaling pathway, can explain experimentally observed disparate localization of subsets of CSCs with varying EMT phenotypes in the tumor. Our simulations show that the more mesenchymal CSCs lie at the invasive edge, while the hybrid epithelial/mesenchymal (E/M) CSCs reside in the tumor interior. Further, motivated by the role of Notch-Jagged signaling in mediating EMT and stemness, we investigated the microenvironmental factors that promote Notch-Jagged signaling. We show that many inflammatory cytokines such as IL-6 that can promote Notch-Jagged signaling can (i) stabilize a hybrid E/M phenotype, (ii) increase the likelihood of spatial proximity of hybrid E/M cells, and (iii) expand the fraction of CSCs. To validate the predicted connection between Notch-Jagged signaling and stemness, we knocked down JAG1 in hybrid E/M SUM149 human breast cancer cells in vitro. JAG1 knockdown significantly restricted tumor organoid formation, confirming the key role that Notch-Jagged signaling can play in tumor progression. Together, our integrated computational-experimental framework reveals the underlying principles of spatiotemporal dynamics of EMT and CSCs.}, } @article {pmid30587588, year = {2019}, author = {Milea, S and Shelley, CD and Weissman, MH}, title = {Arithmetic of arithmetic Coxeter groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {442-449}, doi = {10.1073/pnas.1809537115}, pmid = {30587588}, issn = {1091-6490}, abstract = {In the 1990s, J. H. Conway published a combinatorial-geometric method for analyzing integer-valued binary quadratic forms (BQFs). Using a visualization he named the "topograph," Conway revisited the reduction of BQFs and the solution of quadratic Diophantine equations such as Pell's equation. It appears that the crux of his method is the coincidence between the arithmetic group [Formula: see text] and the Coxeter group of type [Formula: see text] There are many arithmetic Coxeter groups, and each may have unforeseen applications to arithmetic. We introduce Conway's topograph and generalizations to other arithmetic Coxeter groups. This includes a study of "arithmetic flags" and variants of binary quadratic forms.}, } @article {pmid30587587, year = {2019}, author = {Chen, CW and Wang, HL and Huang, CW and Huang, CY and Lim, WK and Tu, IC and Koorapati, A and Hsieh, ST and Kan, HW and Tzeng, SR and Liao, JC and Chong, WM and Naroditzky, I and Kidron, D and Eran, A and Nijim, Y and Sela, E and Feldman, HB and Kalfon, L and Raveh-Barak, H and Falik-Zaccai, TC and Elpeleg, O and Mandel, H and Chang, ZF}, title = {Two separate functions of NME3 critical for cell survival underlie a neurodegenerative disorder.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {566-574}, doi = {10.1073/pnas.1818629116}, pmid = {30587587}, issn = {1091-6490}, abstract = {We report a patient who presented with congenital hypotonia, hypoventilation, and cerebellar histopathological alterations. Exome analysis revealed a homozygous mutation in the initiation codon of the NME3 gene, which encodes an NDP kinase. The initiation-codon mutation leads to deficiency in NME3 protein expression. NME3 is a mitochondrial outer-membrane protein capable of interacting with MFN1/2, and its depletion causes dysfunction in mitochondrial dynamics. Consistently, the patient's fibroblasts were characterized by a slow rate of mitochondrial dynamics, which was reversed by expression of wild-type or catalytic-dead NME3. Moreover, glucose starvation caused mitochondrial fragmentation and cell death in the patient's cells. The expression of wild-type and catalytic-dead but not oligomerization-attenuated NME3 restored mitochondrial elongation. However, only wild-type NME3 sustained ATP production and viability. Thus, the separate functions of NME3 in mitochondrial fusion and NDP kinase cooperate in metabolic adaptation for cell survival in response to glucose starvation. Given the critical role of mitochondrial dynamics and energy requirements in neuronal development, the homozygous mutation in NME3 is linked to a fatal mitochondrial neurodegenerative disorder.}, } @article {pmid30587586, year = {2019}, author = {Plummer, A and Benzi, R and Nelson, DR and Toschi, F}, title = {Fixation probabilities in weakly compressible fluid flows.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {373-378}, doi = {10.1073/pnas.1812829116}, pmid = {30587586}, issn = {1091-6490}, abstract = {Competition between biological species in marine environments is affected by the motion of the surrounding fluid. An effective 2D compressibility can arise, for example, from the convergence and divergence of water masses at the depth at which passively traveling photosynthetic organisms are restricted to live. In this report, we seek to quantitatively study genetics under flow. To this end, we couple an off-lattice agent-based simulation of two populations in 1D to a weakly compressible velocity field-first a sine wave and then a shell model of turbulence. We find for both cases that even in a regime where the overall population structure is approximately unaltered, the flow can significantly diminish the effect of a selective advantage on fixation probabilities. We understand this effect in terms of the enhanced survival of organisms born at sources in the flow and the influence of Fisher genetic waves.}, } @article {pmid30587585, year = {2019}, author = {Jindal, G and Slanska, K and Kolev, V and Damborsky, J and Prokop, Z and Warshel, A}, title = {Exploring the challenges of computational enzyme design by rebuilding the active site of a dehalogenase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {389-394}, doi = {10.1073/pnas.1804979115}, pmid = {30587585}, issn = {1091-6490}, support = {R35 GM122472/GM/NIGMS NIH HHS/United States ; }, abstract = {Rational enzyme design presents a major challenge that has not been overcome by computational approaches. One of the key challenges is the difficulty in assessing the magnitude of the maximum possible catalytic activity. In an attempt to overcome this challenge, we introduce a strategy that takes an active enzyme (assuming that its activity is close to the maximum possible activity), design mutations that reduce the catalytic activity, and then try to restore that catalysis by mutating other residues. Here we take as a test case the enzyme haloalkane dehalogenase (DhlA), with a 1,2-dichloroethane substrate. We start by demonstrating our ability to reproduce the results of single mutations. Next, we design mutations that reduce the enzyme activity and finally design double mutations that are aimed at restoring the activity. Using the computational predictions as a guide, we conduct an experimental study that confirms our prediction in one case and leads to inconclusive results in another case with 1,2-dichloroethane as substrate. Interestingly, one of our predicted double mutants catalyzes dehalogenation of 1,2-dibromoethane more efficiently than the wild-type enzyme.}, } @article {pmid30587584, year = {2019}, author = {Alavash, M and Tune, S and Obleser, J}, title = {Modular reconfiguration of an auditory control brain network supports adaptive listening behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {660-669}, doi = {10.1073/pnas.1815321116}, pmid = {30587584}, issn = {1091-6490}, support = {646696//European Research Council/International ; }, abstract = {Speech comprehension in noisy, multitalker situations poses a challenge. Successful behavioral adaptation to a listening challenge often requires stronger engagement of auditory spatial attention and context-dependent semantic predictions. Human listeners differ substantially in the degree to which they adapt behaviorally and can listen successfully under such circumstances. How cortical networks embody this adaptation, particularly at the individual level, is currently unknown. We here explain this adaptation from reconfiguration of brain networks for a challenging listening task (i.e., a linguistic variant of the Posner paradigm with concurrent speech) in an age-varying sample of n = 49 healthy adults undergoing resting-state and task fMRI. We here provide evidence for the hypothesis that more successful listeners exhibit stronger task-specific reconfiguration (hence, better adaptation) of brain networks. From rest to task, brain networks become reconfigured toward more localized cortical processing characterized by higher topological segregation. This reconfiguration is dominated by the functional division of an auditory and a cingulo-opercular module and the emergence of a conjoined auditory and ventral attention module along bilateral middle and posterior temporal cortices. Supporting our hypothesis, the degree to which modularity of this frontotemporal auditory control network is increased relative to resting state predicts individuals' listening success in states of divided and selective attention. Our findings elucidate how fine-tuned cortical communication dynamics shape selection and comprehension of speech. Our results highlight modularity of the auditory control network as a key organizational principle in cortical implementation of auditory spatial attention in challenging listening situations.}, } @article {pmid30587583, year = {2019}, author = {Kim, M and Paini, D and Jurdak, R}, title = {Modeling stochastic processes in disease spread across a heterogeneous social system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {401-406}, doi = {10.1073/pnas.1801429116}, pmid = {30587583}, issn = {1091-6490}, abstract = {Diffusion processes are governed by external triggers and internal dynamics in complex systems. Timely and cost-effective control of infectious disease spread critically relies on uncovering underlying diffusion mechanisms, which is challenging due to invisible infection pathways and time-evolving intensity of infection cases. Here, we propose a new diffusion framework for stochastic processes, which models disease spread across metapopulations by incorporating human mobility as topological pathways in a heterogeneous social system. We apply Bayesian inference with the stochastic Expectation-Maximization algorithm to quantify underlying diffusion dynamics in terms of exogeneity and endogeneity and estimate cross-regional infection flow based on Granger causality. The effectiveness of our proposed model is shown by using comprehensive simulation procedures (robustness tests with noisy data considering missing or delayed human case reporting in real situations) and by applying the model to real data from 15-y dengue outbreaks in Australia.}, } @article {pmid30587582, year = {2019}, author = {Ha, D and Tanaka, A and Kibayashi, T and Tanemura, A and Sugiyama, D and Wing, JB and Lim, EL and Teng, KWW and Adeegbe, D and Newell, EW and Katayama, I and Nishikawa, H and Sakaguchi, S}, title = {Differential control of human Treg and effector T cells in tumor immunity by Fc-engineered anti-CTLA-4 antibody.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {609-618}, doi = {10.1073/pnas.1812186116}, pmid = {30587582}, issn = {1091-6490}, abstract = {Anti-CTLA-4 mAb is efficacious in enhancing tumor immunity in humans. CTLA-4 is expressed by conventional T cells upon activation and by naturally occurring FOXP3+CD4+ Treg cells constitutively, raising a question of how anti-CTLA-4 mAb can differentially control these functionally opposing T cell populations in tumor immunity. Here we show that FOXP3high potently suppressive effector Treg cells were abundant in melanoma tissues, expressing CTLA-4 at higher levels than tumor-infiltrating CD8+ T cells. Upon in vitro tumor-antigen stimulation of peripheral blood mononuclear cells from healthy individuals or melanoma patients, Fc-region-modified anti-CTLA-4 mAb with high antibody-dependent cell-mediated cytotoxicity (ADCC) and cellular phagocytosis (ADCP) activity selectively depleted CTLA-4+FOXP3+ Treg cells and consequently expanded tumor-antigen-specific CD8+T cells. Importantly, the expansion occurred only when antigen stimulation was delayed several days from the antibody treatment to spare CTLA-4+ activated effector CD8+T cells from mAb-mediated killing. Similarly, in tumor-bearing mice, high-ADCC/ADCP anti-CTLA-4 mAb treatment with delayed tumor-antigen vaccination significantly prolonged their survival and markedly elevated cytokine production by tumor-infiltrating CD8+ T cells, whereas antibody treatment concurrent with vaccination did not. Anti-CTLA-4 mAb modified to exhibit a lesser or no Fc-binding activity failed to show such timing-dependent in vitro and in vivo immune enhancement. Thus, high ADCC anti-CTLA-4 mAb is able to selectively deplete effector Treg cells and evoke tumor immunity depending on the CTLA-4-expressing status of effector CD8+ T cells. These findings are instrumental in designing cancer immunotherapy with mAbs targeting the molecules commonly expressed by FOXP3+ Treg cells and tumor-reactive effector T cells.}, } @article {pmid30587581, year = {2019}, author = {Viswanath, S and Sali, A}, title = {Optimizing model representation for integrative structure determination of macromolecular assemblies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {540-545}, doi = {10.1073/pnas.1814649116}, pmid = {30587581}, issn = {1091-6490}, abstract = {Integrative structure determination of macromolecular assemblies requires specifying the representation of the modeled structure, a scoring function for ranking alternative models based on diverse types of data, and a sampling method for generating these models. Structures are often represented at atomic resolution, although ad hoc simplified representations based on generic guidelines and/or trial and error are also used. In contrast, we introduce here the concept of optimizing representation. To illustrate this concept, the optimal representation is selected from a set of candidate representations based on an objective criterion that depends on varying amounts of information available for different parts of the structure. Specifically, an optimal representation is defined as the highest-resolution representation for which sampling is exhaustive at a precision commensurate with the precision of the representation. Thus, the method does not require an input structure and is applicable to any input information. We consider a space of representations in which a representation is a set of nonoverlapping, variable-length segments (i.e., coarse-grained beads) for each component protein sequence. We also implement a method for efficiently finding an optimal representation in our open-source Integrative Modeling Platform (IMP) software (https://integrativemodeling.org/). The approach is illustrated by application to three complexes of two subunits and a large assembly of 10 subunits. The optimized representation facilitates exhaustive sampling and thus can produce a more accurate model and a more accurate estimate of its uncertainty for larger structures than were possible previously.}, } @article {pmid30587580, year = {2019}, author = {Cowgill, J and Klenchin, VA and Alvarez-Baron, C and Tewari, D and Blair, A and Chanda, B}, title = {Bipolar switching by HCN voltage sensor underlies hyperpolarization activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {670-678}, doi = {10.1073/pnas.1816724116}, pmid = {30587580}, issn = {1091-6490}, abstract = {Despite sharing a common architecture with archetypal voltage-gated ion channels (VGICs), hyperpolarization- and cAMP-activated ion (HCN) channels open upon hyperpolarization rather than depolarization. The basic motions of the voltage sensor and pore gates are conserved, implying that these domains are inversely coupled in HCN channels. Using structure-guided protein engineering, we systematically assembled an array of mosaic channels that display the full complement of voltage-activation phenotypes observed in the VGIC superfamily. Our studies reveal that the voltage sensor of the HCN channel has an intrinsic ability to drive pore opening in either direction and that the extra length of the HCN S4 is not the primary determinant for hyperpolarization activation. Tight interactions at the HCN voltage sensor-pore interface drive the channel into an hERG-like inactivated state, thereby obscuring its opening upon depolarization. This structural element in synergy with the HCN cyclic nucleotide-binding domain and specific interactions near the pore gate biases the channel toward hyperpolarization-dependent opening. Our findings reveal an unexpected common principle underpinning voltage gating in the VGIC superfamily and identify the essential determinants of gating polarity.}, } @article {pmid30587579, year = {2019}, author = {Zhu, L and Lei, J and Klei, L and Devlin, B and Roeder, K}, title = {Semisoft clustering of single-cell data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {466-471}, doi = {10.1073/pnas.1817715116}, pmid = {30587579}, issn = {1091-6490}, abstract = {Motivated by the dynamics of development, in which cells of recognizable types, or pure cell types, transition into other types over time, we propose a method of semisoft clustering that can classify both pure and intermediate cell types from data on gene expression from individual cells. Called semisoft clustering with pure cells (SOUP), this algorithm reveals the clustering structure for both pure cells and transitional cells with soft memberships. SOUP involves a two-step process: Identify the set of pure cells and then estimate a membership matrix. To find pure cells, SOUP uses the special block structure in the expression similarity matrix. Once pure cells are identified, they provide the key information from which the membership matrix can be computed. By modeling cells as a continuous mixture of K discrete types we obtain more parsimonious results than obtained with standard clustering algorithms. Moreover, using soft membership estimates of cell type cluster centers leads to better estimates of developmental trajectories. The strong performance of SOUP is documented via simulation studies, which show its robustness to violations of modeling assumptions. The advantages of SOUP are illustrated by analyses of two independent datasets of gene expression from a large number of cells from fetal brain.}, } @article {pmid30587578, year = {2019}, author = {Kontorovich, A and Nakamura, K}, title = {Geometry and arithmetic of crystallographic sphere packings.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {436-441}, doi = {10.1073/pnas.1721104116}, pmid = {30587578}, issn = {1091-6490}, abstract = {We introduce the notion of a "crystallographic sphere packing," defined to be one whose limit set is that of a geometrically finite hyperbolic reflection group in one higher dimension. We exhibit an infinite family of conformally inequivalent crystallographic packings with all radii being reciprocals of integers. We then prove a result in the opposite direction: the "superintegral" ones exist only in finitely many "commensurability classes," all in, at most, 20 dimensions.}, } @article {pmid30587552, year = {2018}, author = {Fan, J and Meng, J and Ashkenazy, Y and Havlin, S and Schellnhuber, HJ}, title = {Climate network percolation reveals the expansion and weakening of the tropical component under global warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12128-E12134}, doi = {10.1073/pnas.1811068115}, pmid = {30587552}, issn = {1091-6490}, abstract = {Global climate warming poses a significant challenge to humanity; it is associated with, e.g., rising sea level and declining Arctic sea ice. Increasing extreme events are also considered to be a result of climate warming, and they may have widespread and diverse effects on health, agriculture, economics, and political conflicts. Still, the detection and quantification of climate change, both in observations and climate models, constitute a main focus of the scientific community. Here, we develop an approach based on network and percolation frameworks to study the impacts of climate changes in the past decades using historical models and reanalysis records, and we analyze the expected upcoming impacts using various future global warming scenarios. We find an abrupt transition during the evolution of the climate network, indicating a consistent poleward expansion of the largest cluster that corresponds to the tropical area, as well as the weakening of the strength of links in the tropic. This is found both in the reanalysis data and in the Coupled Model Intercomparison Project Phase 5 (CMIP5) 21st century climate change simulations. The analysis is based on high-resolution surface (2 m) air temperature field records. We discuss the underlying mechanism for the observed expansion of the tropical cluster and associate it with changes in atmospheric circulation represented by the weakening and expansion of the Hadley cell. Our framework can also be useful for forecasting the extent of the tropical cluster to detect its influence on different areas in response to global warming.}, } @article {pmid30587550, year = {2018}, author = {Beans, C}, title = {Science and Culture: Journal entries, maps, and photos help ecologists reconstruct ecosystems of the past.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13138-13141}, doi = {10.1073/pnas.1819526115}, pmid = {30587550}, issn = {1091-6490}, } @article {pmid30587392, year = {2018}, author = {Fišer, C}, title = {Collaborative Databasing Should Be Encouraged.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2018.12.001}, pmid = {30587392}, issn = {1872-8383}, } @article {pmid30587379, year = {2018}, author = {Kiaris, H}, title = {Support for Living Stock Collections: A Mammalian Stock Center Perspective.}, journal = {Trends in genetics : TIG}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tig.2018.12.001}, pmid = {30587379}, issn = {0168-9525}, abstract = {The living stock collections represent an indispensable resource for life scientists. Their uninterrupted operation should combine high quality standards, cost-effectiveness, wide accessibility, and sustainability. Mammalian stock collections, especially those involving diversified animals, face some unique challenges that may disrupt their smooth operation if not addressed.}, } @article {pmid30587246, year = {2018}, author = {Lu, T and Ke, M and Lavoie, M and Jin, Y and Fan, X and Zhang, Z and Fu, Z and Sun, L and Gillings, M and Peñuelas, J and Qian, H and Zhu, YG}, title = {Rhizosphere microorganisms can influence the timing of plant flowering.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {231}, doi = {10.1186/s40168-018-0615-0}, pmid = {30587246}, issn = {2049-2618}, support = {N/A//Xingjiang Uighur Autonomous Region Talent Project/ ; 21577128//National Natural Science Foundation of China/ ; N/A//CAS Pioneer Hundred Talents Program/ ; XDB15020402//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 610028//European Research Council/International ; 21777144//National Natural Science Foundation of China/ ; XDB15020302//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, abstract = {BACKGROUND: Plant phenology has crucial biological, physical, and chemical effects on the biosphere. Phenological drivers have largely been studied, but the role of plant microbiota, particularly rhizosphere microbiota, has not been considered.

RESULTS: We discovered that rhizosphere microbial communities could modulate the timing of flowering of Arabidopsis thaliana. Rhizosphere microorganisms that increased and prolonged N bioavailability by nitrification delayed flowering by converting tryptophan to the phytohormone indole acetic acid (IAA), thus downregulating genes that trigger flowering, and stimulating further plant growth. The addition of IAA to hydroponic cultures confirmed this metabolic network.

CONCLUSIONS: We document a novel metabolic network in which soil microbiota influenced plant flowering time, thus shedding light on the key role of soil microbiota on plant functioning. This opens up multiple opportunities for application, from helping to mitigate some of the effects of climate change and environmental stress on plants (e.g. abnormal temperature variation, drought, salinity) to manipulating plant characteristics using microbial inocula to increase crop potential.}, } @article {pmid30587241, year = {2018}, author = {Mu, DS and Liang, QY and Wang, XM and Lu, DC and Shi, MJ and Chen, GJ and Du, ZJ}, title = {Metatranscriptomic and comparative genomic insights into resuscitation mechanisms during enrichment culturing.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {230}, doi = {10.1186/s40168-018-0613-2}, pmid = {30587241}, issn = {2049-2618}, support = {31770002//National Natural Science Foundation of China/ ; 41876166//National Natural Science Foundation of China/ ; 31370057//National Natural Science Foundation of China/ ; 2017FY100302//Science and Technology Basic Resources Investigation Program of China/ ; }, abstract = {BACKGROUND: The pure culture of prokaryotes remains essential to elucidating the role of these organisms. Scientists have reasoned that hard to cultivate microorganisms might grow in pure culture if provided with the chemical components of their natural environment. However, most microbial species in the biosphere that would otherwise be "culturable" may fail to grow because of their growth state in nature, such as dormancy. That means even if scientist would provide microorganisms with the natural environment, such dormant microorganisms probably still remain in a dormant state.

RESULTS: We constructed an enrichment culture system for high-efficiency isolation of uncultured strains from marine sediment. Degree of enrichment analysis, dormant and active taxa calculation, viable but non-culturable bacteria resuscitation analysis, combined with metatranscriptomic and comparative genomic analyses of the interactions between microbial communications during enrichment culture showed that the so-called enrichment method could culture the "uncultured" not only through enriching the abundance of "uncultured," but also through the resuscitation mechanism. In addition, the enrichment culture was a complicated mixed culture system, which contains the competition, cooperation, or coordination among bacterial communities, compared with pure cultures.

CONCLUSIONS: Considering that cultivation techniques must evolve further-from axenic to mixed cultures-for us to fully understand the microbial world, we should redevelop an understanding of the classic enrichment culture method. Enrichment culture methods can be developed and used to construct a model for analyzing mixed cultures and exploring microbial dark matter. This study provides a new train of thought to mining marine microbial dark matter based on mixed cultures.}, } @article {pmid30587239, year = {2018}, author = {Workineh, Y and Birhanu, S and Kerie, S and Ayalew, E and Yihune, M}, title = {Determinants of premature rupture of membrane in Southern Ethiopia, 2017: case control study design.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {927}, doi = {10.1186/s13104-018-4035-9}, pmid = {30587239}, issn = {1756-0500}, abstract = {OBJECTIVE: To identify the determinants of term premature rupture of membrane in Southern Ethiopia public hospitals, 2017.

RESULTS: Seventy-five cases and 223 controls women were enrolled for the study. Two hundred eighty-four (95.3%) participants were admitted at the gestational age of above 40, and the rest, 14 (4.7%), were admitted at 37-40 weeks of gestation. The current study identified wealth index and inter-birth interval as preventive predictors, but smoking and hypertension during pregnancy were identified as positive determinants of premature rupture of membrane. This finding is supported by multiple logistic regression analysis result of wealth index (AOR: 0.102, 95% CI [0.033, 0.315]), inter-birth interval (AOR: 0.251, 95% CI [0.129, 0 0.488]), smoking (AOR: 17.053, 95% CI [2.145, 135.6]), and hypertension (AOR: 8.92, 95% CI (1.91, 41.605]). The association between PROM and its determinants indicated that evidence-based interventions should be needed and designed to have very high wealth index, and optimal interbirth interval, and prevent smoking and hypertension during pregnancy to decrease PROM occurrence in the study settings. Hence, we recommended that integration of prevention mechanism of modifiable determinants to the obstetrics health care system will reduce premature ruptures of a membrane.}, } @article {pmid30587232, year = {2018}, author = {Tesfa, E and Gedamu, H}, title = {Factors associated with utilization of long term family planning methods among women of reproductive age attending Bahir Dar health facilities, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {926}, doi = {10.1186/s13104-018-4031-0}, pmid = {30587232}, issn = {1756-0500}, abstract = {OBJECTIVE: This health institution based cross section study was designed to determine factors associated with utilization of long term family planning methods among women reproductive age attending Bahir Dar health facilities.

RESULT: A total of 406 women were interviewed in this study. The mean age (standard deviation) of the study participants was 26.96 ± 6.31. About 99% of the study participants were consisted from Amhara ethnic group and 60.6% of them urban dwellers. In this study about 90.9% of the study participants had information about LTFP methods and 26.4% of them utilizing the methods. Factors like; knowledge of the women towards LTFP, spousal discussion on FP and occupation of the women affects LTFP utilization (6 times, 3 times and 4 times, respectively) when compared with their counter parts. In addition monthly income of the household was also associated to LTFP methods. In this study less percentage (26.4%) of women's utilizing LTFP methods that were significantly associated with the knowledge of women on LTFP, spousal discussion on FP, occupation of the women and monthly income of the household. As result continuous health education will be recommended.}, } @article {pmid30587231, year = {2018}, author = {Gutema, G and Engidawork, E}, title = {Affordability of commonly prescribed antibiotics in a large tertiary teaching hospital in Ethiopia: a challenge for the national drug policy objective.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {925}, doi = {10.1186/s13104-018-4021-2}, pmid = {30587231}, issn = {1756-0500}, abstract = {OBJECTIVE: In national drug policies of many countries, ensuring availability and affordability of essential medicines is indicated among the major policy objectives. To achieve the objectives, countries with low and middle income compile such medicines into NEMLs. This study aims to determine availability and affordability of commonly prescribed antibiotics at a tertiary hospital in Ethiopia by assessing (in private and public pharmacies) 13 antibiotics constituting DU90% at the hospital.

RESULTS: Availability of the antibiotics in the private and public pharmacies was 92.3% and 98.5%, respectively. Average MPRs for the antibiotics were 4.1 and 2.7, respectively, in the private and public pharmacies. The days' wages (in median prices) ranged from 0.2 for treating acute diarrhea with doxycycline to 415.8 for treating HAP in public pharmacies. Costs of a single day treatment with antibiotics purchased from the public pharmacies ranged from USD 0.1 for acute diarrhea to USD 29.7 for HAP. For the private pharmacies, the range was from USD 0.1 for toxoplasmosis to USD 54.9 for HAP. This study showed that treatments of commonly diagnosed infectious conditions at TASH remain unaffordable according to the WHO/HAI criteria.}, } @article {pmid30587139, year = {2018}, author = {Pi, B and He, X and Ruan, Y and Jang, JC and Huang, Y}, title = {Genome-wide analysis and stress-responsive expression of CCCH zinc finger family genes in Brassica rapa.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {373}, doi = {10.1186/s12870-018-1608-7}, pmid = {30587139}, issn = {1471-2229}, support = {2015//Training Program for Youth Backbone Teacher (for Huang Yong) in University of Hunan (Resistance and Epigenetic Mechanism of Rice and Brassica 2015)/ ; }, abstract = {BACKGROUND: Ubiquitous CCCH nucleic acid-binding motif is found in a wide-variety of organisms. CCCH genes are involved in plant developmental processes and biotic and abiotic stress responses. Brassica rapa is a vital economic crop and classical model plant of polyploidy evolution, but the functions of CCCH genes in B. rapa are unclear.

RESULTS: In this study, 103 CCCH genes in B. rapa were identified. A comparative analysis of the chromosomal position, gene structure, domain organization and duplication event between B. rapa and Arabidopsis thaliana were performed. Results showed that CCCH genes could be divided into 18 subfamilies, and segmental duplication might mainly contribute to this family expansion. C-X7/8-C-X5-C3-H was the most commonly found motif, but some novel CCCH motifs were also found, along with some loses of typical CCCH motifs widespread in other plant species. The multifarious gene structures and domain organizations implicated functional diversity of CCCH genes in B. rapa. Evidence also suggested functional redundancy in at least one subfamily due to high conservation between members. Finally, the expression profiles of subfamily-IX genes indicated that they are likely involved in various stress responses.

CONCLUSION: This study provides the first genome-wide characterization of the CCCH genes in B. rapa. The results suggest that B. rapa CCCH genes are likely functionally divergent, but mostly involved in plant development and stress response. These results are expected to facilitate future functional characterization of this potential RNA-binding protein family in Brassica crops.}, } @article {pmid30587136, year = {2018}, author = {Mager, S and Schönberger, B and Ludewig, U}, title = {The transcriptome of zinc deficient maize roots and its relationship to DNA methylation loss.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {372}, doi = {10.1186/s12870-018-1603-z}, pmid = {30587136}, issn = {1471-2229}, support = {1//Ministerium für Wissenschaft, Forschung und Kunst Baden-Württemberg (DE)/ ; }, abstract = {BACKGROUND: Zinc (Zn) is an essential micronutrient of all organisms. Deficiency of zinc causes disturbance in crucial plant functions, as a high number of enzymes, including transcription factors, depend on zinc for proper performance. The plant responses to zinc deficiency are associated with increased high affinity Zn uptake and translocation, as well as efficient usage of the remaining zinc, but have not been characterized in molecular detail in maize.

RESULTS: The high affinity transporter genes ZmZIP3,4,5,7 and 8 and nicotianamine synthases, primarily ZmNAS5, were identified as primary up-regulated in maize roots upon prolonged Zn deficiency. In addition to down-regulation of genes encoding enzymes involved in pathways regulating reactive oxygen species and cell wall-related genes, a massive up-regulation of the sucrose efflux channel genes SWEET13a,c was identified, despite that in -Zn sugar is known to accumulate in shoots. In addition, enzymes involved in DNA maintenance methylation tended to be repressed, which coincided with massively reduced DNA methylation in Zn-deficient roots. Reduced representation bisulfate sequencing, which revealed base-specific methylation patterns in ~ 14% of the maize genome, identified a major methylation loss in -Zn, mostly in transposable elements. However, hypermethylated genome regions in -Zn were also identified, especially in both symmetrical cytosine contexts. Differential methylation was partially associated with differentially expressed genes, their promoters, or transposons close to regulated genes. However, hypomethylation was associated with about equal number of up- or down-regulated genes, questioning a simple mechanistic relationship to gene expression.

CONCLUSIONS: The transcriptome of Zn-deficient roots identified genes and pathways to cope with the deficiency and a major down-regulation of reactive oxygen metabolism. Interestingly, a nutrient-specific loss of DNA methylation, partially related to gene expression in a context-specific manner, may play a role in long-term stress adaptation.}, } @article {pmid30587132, year = {2018}, author = {Chen, S and Wang, J and Deng, G and Chen, L and Cheng, X and Xu, H and Zhan, K}, title = {Interactive effects of multiple vernalization (Vrn-1)- and photoperiod (Ppd-1)-related genes on the growth habit of bread wheat and their association with heading and flowering time.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {374}, doi = {10.1186/s12870-018-1587-8}, pmid = {30587132}, issn = {1471-2229}, abstract = {BACKGROUND: The precise identification of Winterness/Springness (growth habit) for bread wheat, which is determined by genes involved in vernalization and photoperiod, will contribute to the effective utilization of bread wheat varieties. Here, 198 varieties from the Yellow and Huai wheat production region (YHW) in China were collected to identify their vernalization (Vrn-1) and photoperiod (Ppd-1) gene composition via a series of functional markers and their association with vernalization and photoperiod requirements at three locations during two years of experiments. The growth habits were measured during the spring sowing season.

RESULTS: The results showed that the semi-winter varieties (grades1-4) were most prevalent in the population. The relative effects of single Vrn alleles on the growth period, such as heading date (HD) and/or flowering date (FD), were as follows: Vrn-B1b > Vrn-B1a > Vrn-D1b > Vrn-D1a > vrn-D1 = vrn-B1. The interactive effects of Vrn-B1 and Vrn-D1 on HD and FD were identical to those of Vrn-B1b. Approximately 35.3% of the cultivars carried Ppd-B1a (photoperiod-insensitive) and exhibited the earliest HD and FD. The Ppd-D1a-insensitive allele (Hapl II) was carried by just 0.5% of the varieties; however, the other two sensitive alleles were present at a higher frequency, and their effects were slightly weaker than those of Ppd-B1a. In addition, strong interactive effects between Ppd-B1 and Ppd-D1 were detected. In terms of mean values among various genotypes, the effects followed the order of Vrn-1 > Ppd-1.

CONCLUSIONS: According to the results of ANOVA and least significant range (LSR) tests, we can conclude that Vrn-1 rather than Ppd-1 played a major role in controlling vernalization and photoperiod responses in this region. This research will be helpful for precisely characterizing and evaluating the HD, FD and even growth habit of varieties in the YHW at molecular levels.}, } @article {pmid30587131, year = {2018}, author = {Guo, X and Wang, H and Cheng, Y and Zhang, W and Luo, Q and Wen, G and Wang, G and Shao, H and Zhang, T}, title = {Quinolone resistance phenotype and genetic characterization of Salmonella enterica serovar Pullorum isolates in China, during 2011 to 2016.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {225}, doi = {10.1186/s12866-018-1368-4}, pmid = {30587131}, issn = {1471-2180}, abstract = {BACKGROUND: Pullorum disease, caused by Salmonella enterica serovar Pullorum (S. Pullorum), is one of the most important bacterial infections in the poultry industry in developing countries, including China. To examine the prevalence and characteristics of S. Pullorum, the Multilocus Sequence Typing (MLST) genotypes, fluoroquinolones resistance, and biofilm-forming abilities of S. Pullorum isolates were investigated, collected from 2011 to 2016 in China.

RESULTS: Thirty S. Pullorum isolates collected from 2011 to 2016 were analyzed. Quinolones susceptibility testing showed that 90% of the isolates were resistant to the first generation of quinolines nalidixic acid, but the resistance rates to different fluoroquinolones agents were lower than 13.3%; for some there was even no resistance. Multilocus sequence typing (MLST) showed that ST-92 was the dominating genotype, accounting for 90.0% of all S. pullorum strains. The remaining three isolates were of the new reported sequence type ST-2151. Interestingly, the Asp87Gly substitution in quinolone resistance-determining regions (QRDR) of GyrA was only observed in the three strains of ST-2151, suggesting a potential correlation between Asp87Gly substitution and sequence type (p < 0.05). However, Asp87Gly substitution could not confer the resistant to ofloxacin and ciprofloxacin of these isolates. The plasmid-mediated quinolone resistance (PMQR) gene was not found in any of the tested isolates. Furthermore, an assay measuring biofilm-forming abilities showed that 46.7% of the isolates were non-biofilm producers, while 53.3% could form very weak biofilms, which might explain the relatively lower resistance to fluoroquinolones.

CONCLUSIONS: We reported a high resistance rate to the first generation of quinolines nalidixic acid and relatively low resistance rates to fluoroquinolones in S. Pullorum isolates. In addition, weak biofilm-forming abilities were found, which might be an important reason of the low fluoroquinolones resistance rates of S. Pullorum isolates. ST-92 was the dominating genotype demonstrated by MLST, and the new sequence type ST-2151 showed a potential correlation with Asp87Gly substitution in QRDR of GyrA. We believe the characterization of these S. Pullorum isolates will be helpful to develop prevention and control strategies.}, } @article {pmid30587130, year = {2018}, author = {Borghini, L and Hibberd, M and Davila, S}, title = {Changes in H3K27ac following lipopolysaccharide stimulation of nasopharyngeal epithelial cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {969}, doi = {10.1186/s12864-018-5295-4}, pmid = {30587130}, issn = {1471-2164}, support = {SINGA scholarship//Agency for Science, Technology and Research/ ; }, abstract = {BACKGROUND: The epithelium is the first line of defense against pathogens. Notably the epithelial cells lining the respiratory track are crucial in sensing airborne microbes and mounting an effective immune response via the expression of target genes such as cytokines and chemokines. Gene expression regulation following microbial recognition is partly regulated by chromatin re-organization and has been described in immune cells but data from epithelial cells is not as detailed. Here, we report genome-wide changes of the H3K27ac mark, characteristic of activated enhancers and promoters, after stimulation of nasopharyngeal epithelial cells with the bacterial endotoxin Lipopolysaccharide (LPS).

RESULTS: In this study, we have identified 626 regions where the H3K27ac mark showed reproducible increase following LPS induction in epithelial cells. This indicated that sensing of LPS led to opening of the chromatin in our system. Moreover, this phenomenon seemed to happen extensively at enhancers regions and we could observe instances of Super-enhancer formation. As expected, LPS-increased H3K27ac regions were found in the vicinity of genes relevant for LPS response and these changes correlated with up-regulation of their expression. In addition, we found the induction of H3K27ac mark to overlap with the binding of one of the NF-kB members and key regulator of the innate immune response, RELA, following LPS sensing. Indeed, inhibiting the NF-kB pathway abolished the deposition of H3K27ac at the TNF locus, a target of RELA, suggesting that these two phenomena are associated.

CONCLUSIONS: Enhancers' selection and activation following microbial or inflammatory stimuli has been described previously and shown to be mediated via the NF-kB pathway. Here, we demonstrate that this is also likely to occur in the case of LPS-sensing by nasopharyngeal epithelial cells as well. In addition to validating previous findings, we generated a valuable data set relevant to the host immune response to epithelial cell colonizing or infecting pathogens.}, } @article {pmid30587129, year = {2018}, author = {Kang, K and Yang, P and Chen, LE and Pang, R and Yu, LJ and Zhou, WW and Zhu, ZR and Zhang, WQ}, title = {Identification of putative fecundity-related gustatory receptor genes in the brown planthopper Nilaparvata lugens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {970}, doi = {10.1186/s12864-018-5391-5}, pmid = {30587129}, issn = {1471-2164}, support = {U1401212//National Natural Science Foundation of China/ ; 2017M612808//China Postdoctoral Science Foundation (CN)/ ; }, abstract = {BACKGROUND: The insect gustatory system plays a central role in the regulation of multiple physiological behaviors and the co-evolution between insects and their hosts. The gustatory receptors (Gr) are important to allow insects to sense their environment. It is critical to the selection of foods, mates and oviposition sites of insects. In this study, the Gr family genes of the brown planthopper (BPH) Nilaparvata lugens Stål (Hemiptera: Delphacidae) were identified and analyzed, and their potential relationship to the fecundity of BPH was explored by RNA interference (RNAi).

RESULTS: We identified 32 putative Gr genes by analyzing transcriptome and genome data from BPH. Most of these Gr proteins have the typical structure of seven transmembrane domains. The BPH Gr genes (NlGrs) were expressed in virtually all tissues and stages, whilst higher transcript accumulations were found in adult stages and in the midguts of females. Based on the phylogenic analysis, we classified NlGrs into five potential categories, including 2 sugar receptors, 2 Gr43a-like receptors, 7 CO2 receptors, 5 bitter receptors and 13 NlGrs with unknown functions. Moreover, we found that 10 NlGrs have at least two alternative splicing variants, and obtained alternative splicing isoforms of 5 NlGrs. Finally, RNAi of 29 NlGrs showed that 27 of them are related to the transcript levels of two fecundity related genes vitellogenin and vitellogenin receptor.

CONCLUSIONS: We found 32 Gr genes in BPH, among which at least 27 are required for normal expression of fecundity markers of this insect pest. These findings provide the basis for the functional study of Grs and the exploration of potential genes involved in the monophagous character of BPH.}, } @article {pmid30587128, year = {2018}, author = {Li, JR and Liu, CC and Sun, CH and Chen, YT}, title = {Plant stress RNA-seq Nexus: a stress-specific transcriptome database in plant cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {966}, doi = {10.1186/s12864-018-5367-5}, pmid = {30587128}, issn = {1471-2164}, support = {MOST 106-2311-B-005-005//Ministry of Science and Technology, Taiwan/ ; MOST 106-2313-B-005 -035 -MY2//Ministry of Science and Technology, Taiwan/ ; Advanced Plant Biotechnology Center from The Featured Areas Research Center Program within the framework of the Higher Education Sprout Project//Ministry of Education/ ; }, abstract = {BACKGROUND: Abiotic and biotic stresses severely affect the growth and reproduction of plants and crops. Determining the critical molecular mechanisms and cellular processes in response to stresses will provide biological insight for addressing both climate change and food crises. RNA sequencing (RNA-Seq) is a revolutionary tool that has been used extensively in plant stress research. However, no existing large-scale RNA-Seq database has been designed to provide information on the stress-specific differentially expressed transcripts that occur across diverse plant species and various stresses.

RESULTS: We have constructed a comprehensive database, the plant stress RNA-Seq nexus (PSRN), which includes 12 plant species, 26 plant-stress RNA-Seq datasets, and 937 samples. All samples are assigned to 133 stress-specific subsets, which are constructed into 254 subset pairs, a comparison between selected two subsets, for stress-specific differentially expressed transcript identification.

CONCLUSIONS: PSRN is an open resource for intuitive data exploration, providing expression profiles of coding-transcript/lncRNA and identifying which transcripts are differentially expressed between different stress-specific subsets, in order to support researchers generating new biological insights and hypotheses in molecular breeding or evolution. PSRN is freely available at http://syslab5.nchu.edu.tw/PSRN .}, } @article {pmid30587127, year = {2018}, author = {Hou, Y and Liang, D and Liu, Y and Chen, H and Lou, X}, title = {Up-regulation of DcR3 in microbial toxins-stimulated HUVECs involves NF-κB signalling.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {13}, doi = {10.1186/s12858-018-0102-z}, pmid = {30587127}, issn = {1471-2091}, support = {201540119//Scientific Foundation of Shanghai Municipal Commission of Health and Family Planning/ ; 20164Y0273//Scientific Foundation of Shanghai Municipal Commission of Health and Family Planning/ ; NO. 15SJGG25 and NO.15SJGG47//Science and Technology Research Project of Songjiang District of Shanghai/ ; 81602131//National Natural Science Foundation of China/ ; 81702729//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Sepsis is a severe condition characterised by the body's systemic inflammatory response to infection. The specific sepsis-related biomarkers should be used in clinical diagnosis, therapeutic response monitoring, rational use of antibiotics, and prognosis (risk stratification), etc. RESULTS: In this study, we investigated the expression level of Decoy Receptor 3 (DcR3) and the mechanism of high expression in sepsis patients. Septic cell model experiments were performed by treating human umbilical vein endothelial cells (HUVECs) and Jurkat cells with lipopolysaccharide (LPS), lipoteichoic acid (LTA) and zymosan, respectively. SP600125, SB203580 and ammonium pyrrolidinedithiocarbamate (PDTC) were used to inhibit JNK1/2, p38MAPK and NF-κB signalling pathways in septic cell model, respectively. These results showed that DcR3 levels were higher in sepsis group than control. DcR3 mRNA and protein levels in HUVECs were increased following treatment with LPS, LTA and zymosan, and also increased in Jurkat cells treated by LPS, but not by LTA or zymosan. When HUVECs were treated with the NF-κB inhibitor PDTC, DcR3 expression was decreased compared with controls. However, SP600125 and SB203580 had no effect on DcR3 mRNA or protein levels.

CONCLUSIONS: The results indicated that DcR3 secretion proceeded through the NF-κB signalling pathway in HUVECs.}, } @article {pmid30587126, year = {2018}, author = {Bochkareva, OO and Moroz, EV and Davydov, II and Gelfand, MS}, title = {Genome rearrangements and selection in multi-chromosome bacteria Burkholderia spp.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {965}, doi = {10.1186/s12864-018-5245-1}, pmid = {30587126}, issn = {1471-2164}, support = {18-14-00358//Russian Science Foundation/ ; 16-54-21004//Russian Foundation of Basic Research/ ; IZLRZ3\163872//Swiss National Science Foundation/ ; }, abstract = {BACKGROUND: The genus Burkholderia consists of species that occupy remarkably diverse ecological niches. Its best known members are important pathogens, B. mallei and B. pseudomallei, which cause glanders and melioidosis, respectively. Burkholderia genomes are unusual due to their multichromosomal organization, generally comprised of 2-3 chromosomes.

RESULTS: We performed integrated genomic analysis of 127 Burkholderia strains. The pan-genome is open with the saturation to be reached between 86,000 and 88,000 genes. The reconstructed rearrangements indicate a strong avoidance of intra-replichore inversions that is likely caused by selection against the transfer of large groups of genes between the leading and the lagging strands. Translocated genes also tend to retain their position in the leading or the lagging strand, and this selection is stronger for large syntenies. Integrated reconstruction of chromosome rearrangements in the context of strains phylogeny reveals parallel rearrangements that may indicate inversion-based phase variation and integration of new genomic islands. In particular, we detected parallel inversions in the second chromosomes of B. pseudomallei with breakpoints formed by genes encoding membrane components of multidrug resistance complex, that may be linked to a phase variation mechanism. Two genomic islands, spreading horizontally between chromosomes, were detected in the B. cepacia group.

CONCLUSIONS: This study demonstrates the power of integrated analysis of pan-genomes, chromosome rearrangements, and selection regimes. Non-random inversion patterns indicate selective pressure, inversions are particularly frequent in a recent pathogen B. mallei, and, together with periods of positive selection at other branches, may indicate adaptation to new niches. One such adaptation could be a possible phase variation mechanism in B. pseudomallei.}, } @article {pmid30587123, year = {2018}, author = {Zheng, L and Ma, J and Mao, J and Fan, S and Zhang, D and Zhao, C and An, N and Han, M}, title = {Genome-wide identification of SERK genes in apple and analyses of their role in stress responses and growth.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {962}, doi = {10.1186/s12864-018-5342-1}, pmid = {30587123}, issn = {1471-2164}, support = {2013BAD20B03//National Science and Technology Supporting Project/ ; CARS-28//National Apple Industry Technology System of Agriculture Ministry of China/ ; 2016TZC-N-11-6//the Innovation project of science and technology of Shaanxi Province/ ; 2017ZDXM-NY-019//the key research project of Shaanxi provincial/ ; }, abstract = {BACKGROUND: Somatic embryogenesis receptor-like kinases (SERKs) are leucine-rich repeat receptor-like kinases associated with various signaling pathways. These kinases have a relationship with stress signals, and they are also believed to be important for regulating plant growth. However, information about this protein family in apple is limited.

RESULTS: Twelve apple SERK genes distributed across eight chromosomes were identified. These genes clustered into three distinct groups in a phylogenetic analysis. All of the encoded proteins contained typical SERK domains. The chromosomal locations, gene/protein structures, synteny, promoter sequences, protein-protein interactions, and physicochemical characteristics of MdSERK genes were analyzed. Bioinformatics analyses demonstrated that gene duplications have likely contributed to the expansion and evolution of SERK genes in the apple genome. Six homologs of SERK genes were identified between apple and Arabidopsis. Quantitative real-time PCR analyses revealed that the MdSERK genes showed different expression patterns in various tissues. Eight MdSERK genes were responsive to stress signals, such as methyl jasmonate, salicylic acid, abscisic acid, and salt (NaCl). The application of exogenous brassinosteroid and auxin increased the growth and endogenous hormone contents of Malus hupehensis seedlings. The expression levels of seven MdSERK genes were significantly upregulated by brassinosteroid and auxin. In addition, several MdSERK genes showed higher expression levels in standard trees of 'Nagafu 2' (CF)/CF than in dwarf trees of CF/'Malling 9' (M.9), and in CF than in the spur-type bud mutation "Yanfu 6" (YF).

CONCLUSION: This study represents the first comprehensive investigation of the apple SERK gene family. These data indicate that apple SERKs may function in adaptation to adverse environmental conditions and may also play roles in controlling apple tree growth.}, } @article {pmid30587122, year = {2018}, author = {Guerra, PR and Herrero-Fresno, A and Ladero, V and Redruello, B and Dos Santos, TP and Spiegelhauer, MR and Jelsbak, L and Olsen, JE}, title = {Putrescine biosynthesis and export genes are essential for normal growth of avian pathogenic Escherichia coli.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {226}, doi = {10.1186/s12866-018-1355-9}, pmid = {30587122}, issn = {1471-2180}, support = {DFF - 4184-00050//Teknologi og Produktion, Det Frie Forskningsr&x00E5;d/ ; AGL2013-45431-R/ AGL2016-78708-R//Spanish Ministry of Economy, Industry, and Competitiveness/ ; 99999.013215/2013-02//CAPES- Brazilian Federal Agency for Support and Evaluation of Graduate Education within the Ministry of Education of Brazil/ ; }, abstract = {BACKGROUND: Avian pathogenic Escherichia coli (APEC) is the infectious agent of a wide variety of avian diseases, which causes substantial economic losses to the poultry industry worldwide. Polyamines contribute to the optimal synthesis of nucleic acids and proteins in bacteria. The objectives of this study were to investigate; i) whether APEC E. coli encodes the same systems for biosynthesis and uptake as described for E. coli K12 and ii) the role of polyamines during in vitro growth of an avian pathogenic E. coli strain (WT-ST117- O83:H4T).

RESULTS: Following whole genome sequencing, polyamine biosynthesis and export genes present in E. coli MG1655 (K-12) were found to be identical in WT-ST117. Defined mutants were constructed in putrescine and spermidine biosynthesis pathways (ΔspeB, ΔspeC, ΔspeF, ΔspeB/C and ΔspeD/E), and in polyamines transport systems (ΔpotE, ΔyeeF, ΔpotABCD and ΔpotFGHI). Contrary to what was observed for MG1655, the ΔpotE-ST117 mutant was growth attenuated, regardless of putrescine supplementation. The addition of spermidine or orthinine restored the growth to the level of WT-ST117. Growth attenuation after induction of membrane stress by SDS suggested that PotE is involved in protection against this stress. The ΔspeB/C-ST117 mutant was also growth attenuated in minimal medium. The addition of putrescine or spermidine to the media restored growth rate to the wild type level. The remaining biosynthesis and transport mutants showed a growth similar to that of WT-ST117. Analysis by Ultra-High Performance Liquid Chromatography revealed that the ΔspeB/C mutant was putrescine-deficient, despite that the gene speF, which is also involved in the synthesis of putrescine, was expressed.

CONCLUSIONS: Deletion of the putrescine transport system, PotE, or the putrescine biosynthesis pathway genes speB/C affected in vitro growth of APEC (ST117- O83:H4) strain, but not E. coli MG1655, despite the high similarity of the genetic make-up of biosynthesis and transport genes. Therefore, blocking these metabolic reactions may be a suitable way to prevent APEC growth in the host without disturbing the commensal E. coli population.}, } @article {pmid30587121, year = {2018}, author = {Skoko, J and Rožanc, J and Charles, EM and Alexopoulos, LG and Rehm, M}, title = {Post-treatment de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {28}, doi = {10.1186/s12860-018-0180-1}, pmid = {30587121}, issn = {1471-2121}, support = {642295//Horizon 2020 Framework Programme/ ; 642295//Horizon 2020/ ; HRA-POR-2013-245//Health Research Board/Ireland ; HRA-POR-2015-1091//Health Research Board/Ireland ; }, abstract = {BACKGROUND: Dasatinib (Sprycel) was developed as a tyrosine kinase inhibitor targeting Bcr-Abl and the family of Src kinases. Dasatinib is commonly used for the treatment of acute lymphoblastic and chronic myelogenous leukemia. Previous clinical studies in melanoma returned inconclusive results and suggested that patients respond highly heterogeneously to dasatinib as single agent or in combination with standard-of-care chemotherapeutic dacarbazine. Reliable biomarkers to predict dasatinib responsiveness in melanoma have not yet been developed.

RESULTS: Here, we collected comprehensive in vitro data from experimentally well-controlled conditions to study the effect of dasatinib, alone and in combination with dacarbazine, on cell proliferation and cell survival. Sixteen treatment conditions, covering therapeutically relevant concentrations ranges of both drugs, were tested in 12 melanoma cell lines with diverse mutational backgrounds. Melanoma cell lines responded heterogeneously and, importantly, dasatinib and dacarbazine did not synergize in suppressing proliferation or inducing cell death. Since dasatinib is a promiscuous kinase inhibitor, possibly affecting multiple disease-relevant pathways, we also determined if basal phospho-protein amounts and treatment-induced changes in phospho-protein levels are indicative of dasatinib responsiveness. We found that treatment-induced de-phosphorylation of p53 correlates with dasatinib responsiveness in malignant melanoma.

CONCLUSIONS: Loss of p53 phosphorylation might be an interesting candidate for a kinetic marker of dasatinib responsiveness in melanoma, pending more comprehensive validation in future studies.}, } @article {pmid30587120, year = {2018}, author = {Giacopuzzi, E and Gennarelli, M and Sacco, C and Filippini, A and Mingardi, J and Magri, C and Barbon, A}, title = {Genome-wide analysis of consistently RNA edited sites in human blood reveals interactions with mRNA processing genes and suggests correlations with cell types and biological variables.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {963}, doi = {10.1186/s12864-018-5364-8}, pmid = {30587120}, issn = {1471-2164}, support = {R01 MH090941/MH/NIMH NIH HHS/United States ; RC2 MH089916/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: A-to-I RNA editing is a co-/post-transcriptional modification catalyzed by ADAR enzymes, that deaminates Adenosines (A) into Inosines (I). Most of known editing events are located within inverted ALU repeats, but they also occur in coding sequences and may alter the function of encoded proteins. RNA editing contributes to generate transcriptomic diversity and it is found altered in cancer, autoimmune and neurological disorders. Emerging evidences indicate that editing process could be influenced by genetic variations, biological and environmental variables.

RESULTS: We analyzed RNA editing levels in human blood using RNA-seq data from 459 healthy individuals and identified 2079 sites consistently edited in this tissue. As expected, analysis of gene expression revealed that ADAR is the major contributor to editing on these sites, explaining ~ 13% of observed variability. After removing ADAR effect, we found significant associations for 1122 genes, mainly involved in RNA processing. These genes were significantly enriched in genes encoding proteins interacting with ADARs, including 276 potential ADARs interactors and 9 ADARs direct partners. In addition, our analysis revealed several factors potentially influencing RNA editing in blood, including cell composition, age, Body Mass Index, smoke and alcohol consumption. Finally, we identified genetic loci associated with editing levels, including known ADAR eQTLs and a small region on chromosome 7, containing LOC730338, a lincRNA gene that appears to modulate ADARs mRNA expression.

CONCLUSIONS: Our data provides a detailed picture of the most relevant RNA editing events and their variability in human blood, giving interesting insights on potential mechanisms behind this post-transcriptional modification and its regulation in this tissue.}, } @article {pmid30587119, year = {2018}, author = {Hu, J and Wang, X and Xing, Y and Rong, E and Ning, M and Smith, J and Huang, Y}, title = {Origin and development of oligoadenylate synthetase immune system.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {201}, doi = {10.1186/s12862-018-1315-x}, pmid = {30587119}, issn = {1471-2148}, abstract = {BACKGROUND: Oligoadenylate synthetases (OASs) are widely distributed in Metazoa including sponges, fish, reptiles, birds and mammals and show large variation, with one to twelve members in any given species. Upon double-stranded RNA (dsRNA) binding, avian and mammalian OASs generate the second messenger 2'-5'-linked oligoadenylate (2-5A), which activates ribonuclease L (RNaseL) and blocks viral replication. However, how Metazoa shape their OAS repertoires to keep evolutionary balance to virus infection is largely unknown. We performed comprehensive phylogenetic and functional analyses of OAS genes from evolutionarily lower to higher Metazoa to demonstrate how the OAS repertoires have developed anti-viral activity and diversified their functions.

RESULTS: Ancient Metazoa harbor OAS genes, but lack both upstream and downstream genes of the OAS-related pathways, indicating that ancient OASs are not interferon-induced genes involved in the innate immune system. Compared to OASs of ancient Metazoa (i.e. sponge), the corresponding ones of higher Metazoa present an increasing number of basic residues on the OAS/dsRNA interaction interface. Such an increase of basic residues might improve their binding affinity to dsRNA. Moreover, mutations of functional residues in the active pocket might lead to the fact that higher Metazoan OASs lose the ability to produce 3'-5'-linked oligoadenylate (3-5A) and turn into specific 2-5A synthetases. In addition, we found that multiple rounds of gene duplication and domain coupling events occurred in the OAS family and mutations at functionally critical sites were observed in most new OAS members.

CONCLUSIONS: We propose a model for the expansion of OAS members and provide comprehensive evidence of subsequent neo-functionalization and sub-functionalization. Our observations lay the foundation for interrogating the evolutionary transition of ancient OAS genes to host defense genes and provide important information for exploring the unknown function of the OAS gene family.}, } @article {pmid30587118, year = {2018}, author = {Su, T and He, B and Li, K and Liang, A}, title = {Comparative analysis of the mitochondrial genomes of oriental spittlebug trible Cosmoscartini: insights into the relationships among closely related taxa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {961}, doi = {10.1186/s12864-018-5365-7}, pmid = {30587118}, issn = {1471-2164}, support = {31572298//National Natural Science Foundation of China/ ; 31561163003//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Cosmoscartini (Hemiptera: Cercopoidea: Cercopidae) is a large and brightly colored Old World tropical tribe, currently containing over 310 phytophagous species (including some economically important pests of eucalyptus in China) in approximately 17 genera. However, very limited information of Cosmoscartini is available except for some scattered taxonomic studies. Even less is known about its phylogenetic relationship, especially among closely related genera or species. In this study, the detailed comparative genomic and phylogenetic analyses were performed on nine newly sequenced mitochondrial genomes (mitogenomes) of Cosmoscartini, with the purpose of exploring the taxonomic status of the previously defined genus Okiscarta and some closely related species within the genus Cosmoscarta.

RESULTS: Mitogenomes of Cosmoscartini display similar genomic characters in terms of gene arrangement, nucleotide composition, codon usage and overlapping regions. However, there are also many differences in intergenic spacers, mismatches of tRNAs, and the control region. Additionally, the secondary structures of rRNAs within Cercopidae are inferred for the first time. Based on comparative genomic (especially for the substitution pattern of tRNA secondary structure) and phylogenetic analyses, the representative species of Okiscarta uchidae possesses similar structures with other Cosmoscarta species and is placed consistently in Cosmoscarta. Although Cosmoscarta bimacula is difficult to be distinguished from Cosmoscarta bispecularis by traditional morphological methods, evidence from mitogenomes highly support the relationships of (C. bimacula + Cosmoscarta rubroscutellata) + (C. bispecularis + Cosmoscarta sp.).

CONCLUSIONS: This study presents mitogenomes of nine Cosmoscartini species and represents the first detailed comparative genomic and phylogenetic analyses within Cercopidae. It is indicated that knowledge of mitogenomes can be effectively used to resolve phylogenetic relationships at low taxonomic levels. Sequencing more mitogenomes at various taxonomic levels will also improve our understanding of mitogenomic evolution and phylogeny in Cercopidae.}, } @article {pmid30587117, year = {2018}, author = {Hori, Y and Tanimoto, Y and Takahashi, S and Furukawa, T and Koshiba-Takeuchi, K and Takeuchi, JK}, title = {Important cardiac transcription factor genes are accompanied by bidirectional long non-coding RNAs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {967}, doi = {10.1186/s12864-018-5233-5}, pmid = {30587117}, issn = {1471-2164}, support = {15J11617//Japan Society for the Promotion of Science/ ; LS029//Japan Society for the Promotion of Science/ ; 25291049//Japan Society for the Promotion of Science/ ; 25291049//Ministry of Education, Culture, Sports, Science and Technology/ ; }, abstract = {BACKGROUND: Heart development is a relatively fragile process in which many transcription factor genes show dose-sensitive characteristics such as haploinsufficiency and lower penetrance. Despite efforts to unravel the genetic mechanism for overcoming the fragility under normal conditions, our understanding still remains in its infancy. Recent studies on the regulatory mechanisms governing gene expression in mammals have revealed that long non-coding RNAs (lncRNAs) are important modulators at the transcriptional and translational levels. Based on the hypothesis that lncRNAs also play important roles in mouse heart development, we attempted to comprehensively identify lncRNAs by comparing the embryonic and adult mouse heart and brain.

RESULTS: We have identified spliced lncRNAs that are expressed during development and found that lncRNAs that are expressed in the heart but not in the brain are located close to genes that are important for heart development. Furthermore, we found that many important cardiac transcription factor genes are located in close proximity to lncRNAs. Importantly, many of the lncRNAs are divergently transcribed from the promoter of these genes. Since the lncRNA divergently transcribed from Tbx5 is highly evolutionarily conserved, we focused on and analyzed the transcript. We found that this lncRNA exhibits a different expression pattern than that of Tbx5, and knockdown of this lncRNA leads to embryonic lethality.

CONCLUSION: These results suggest that spliced lncRNAs, particularly bidirectional lncRNAs, are essential regulators of mouse heart development, potentially through the regulation of neighboring transcription factor genes.}, } @article {pmid30587116, year = {2018}, author = {Zhao, X and Tian, K and Yau, SS}, title = {A new efficient method for analyzing fungi species using correlations between nucleotides.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {200}, doi = {10.1186/s12862-018-1330-y}, pmid = {30587116}, issn = {1471-2148}, abstract = {BACKGROUND: In recent years, DNA barcoding has become an important tool for biologists to identify species and understand their natural biodiversity. The complexity of barcode data makes it difficult to analyze quickly and effectively. Manual classification of this data cannot keep up to the rate of increase of available data.

RESULTS: In this study, we propose a new method for DNA barcode classification based on the distribution of nucleotides within the sequence. By adding the covariance of nucleotides to the original natural vector, this augmented 18-dimensional natural vector makes good use of the available information in the DNA sequence. The accurate classification results we obtained demonstrate that this new 18-dimensional natural vector method, together with the random forest classifier algorthm, can serve as a computationally efficient identification tool for DNA barcodes. We performed phylogenetic analysis on the genus Megacollybia to validate our method. We also studied how effective our method was in determining the genetic distance within and between species in our barcoding dataset.

CONCLUSIONS: The classification performs well on the fungi barcode dataset with high and robust accuracy. The reasonable phylogenetic trees we obtained further validate our methods. This method is alignment-free and does not depend on any model assumption, and it will become a powerful tool for classification and evolutionary analysis.}, } @article {pmid30587115, year = {2018}, author = {Gao, J and Sundström, G and Moghadam, BT and Zamani, N and Grabherr, MG}, title = {ACES: a machine learning toolbox for clustering analysis and visualization.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {964}, doi = {10.1186/s12864-018-5300-y}, pmid = {30587115}, issn = {1471-2164}, abstract = {BACKGROUND: Studies that aim at explaining phenotypes or disease susceptibility by genetic or epigenetic variants often rely on clustering methods to stratify individuals or samples. While statistical associations may point at increased risk for certain parts of the population, the ultimate goal is to make precise predictions for each individual. This necessitates tools that allow for the rapid inspection of each data point, in particular to find explanations for outliers.

RESULTS: ACES is an integrative cluster- and phenotype-browser, which implements standard clustering methods, as well as multiple visualization methods in which all sample information can be displayed quickly. In addition, ACES can automatically mine a list of phenotypes for cluster enrichment, whereby the number of clusters and their boundaries are estimated by a novel method. For visual data browsing, ACES provides a 2D or 3D PCA or Heat Map view. ACES is implemented in Java, with a focus on a user-friendly, interactive, graphical interface.

CONCLUSIONS: ACES has been proven an invaluable tool for analyzing large, pre-filtered DNA methylation data sets and RNA-Sequencing data, due to its ease to link molecular markers to complex phenotypes. The source code is available from https://github.com/GrabherrGroup/ACES .}, } @article {pmid30587114, year = {2018}, author = {Tyakht, AV and Manolov, AI and Kanygina, AV and Ischenko, DS and Kovarsky, BA and Popenko, AS and Pavlenko, AV and Elizarova, AV and Rakitina, DV and Baikova, JP and Ladygina, VG and Kostryukova, ES and Karpova, IY and Semashko, TA and Larin, AK and Grigoryeva, TV and Sinyagina, MN and Malanin, SY and Shcherbakov, PL and Kharitonova, AY and Khalif, IL and Shapina, MV and Maev, IV and Andreev, DN and Belousova, EA and Buzunova, YM and Alexeev, DG and Govorun, VM}, title = {Genetic diversity of Escherichia coli in gut microbiota of patients with Crohn's disease discovered using metagenomic and genomic analyses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {968}, doi = {10.1186/s12864-018-5306-5}, pmid = {30587114}, issn = {1471-2164}, support = {16-15-00258//Russian Science Foundation/ ; }, abstract = {BACKGROUND: Crohn's disease is associated with gut dysbiosis. Independent studies have shown an increase in the abundance of certain bacterial species, particularly Escherichia coli with the adherent-invasive pathotype, in the gut. The role of these species in this disease needs to be elucidated.

METHODS: We performed a metagenomic study investigating the gut microbiota of patients with Crohn's disease. A metagenomic reconstruction of the consensus genome content of the species was used to assess the genetic variability.

RESULTS: The abnormal shifts in the microbial community structures in Crohn's disease were heterogeneous among the patients. The metagenomic data suggested the existence of multiple E. coli strains within individual patients. We discovered that the genetic diversity of the species was high and that only a few samples manifested similarity to the adherent-invasive varieties. The other species demonstrated genetic diversity comparable to that observed in the healthy subjects. Our results were supported by a comparison of the sequenced genomes of isolates from the same microbiota samples and a meta-analysis of published gut metagenomes.

CONCLUSIONS: The genomic diversity of Crohn's disease-associated E. coli within and among the patients paves the way towards an understanding of the microbial mechanisms underlying the onset and progression of the Crohn's disease and the development of new strategies for the prevention and treatment of this disease.}, } @article {pmid30587113, year = {2018}, author = {Hou, P and Wang, H and Zhao, G and Hu, G and Xia, X and He, H}, title = {MiR-3470b promotes bovine ephemeral fever virus replication via directly targeting mitochondrial antiviral signaling protein (MAVS) in baby hamster Syrian kidney cells.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {224}, doi = {10.1186/s12866-018-1366-6}, pmid = {30587113}, issn = {1471-2180}, support = {31502064//National Natural Science Fund of China/ ; 31672556//National Natural Science Fund of China/ ; 2018GNC113011//the Shandong province Key R & D program Fund/ ; 2016GNC113006//Primary Research & Developement Plan of Shandong Province/ ; }, abstract = {BACKGROUND: Bovine ephemeral fever virus (BEFV), the causative agent of bovine ephemeral fever, is an economically important pathogen of cattle and water buffalo. MicroRNAs (miRNAs) are endogenous 21-23 nt small non-coding RNA molecules that binding to a multiple of target mRNAs and functioning in the regulation of viral replication including the miRNA-mediated antiviral defense. However, the reciprocal interaction between bovine ephemeral fever virus replication and host miRNAs still remain poorly understood. The aim of our study herein was to investigate the exact function of miR-3470b and its molecular mechanisms during BEFV infection.

RESULTS: In this study, we found a set of microRNAs induced by BEFV infection using small RNA deep sequencing, and further identified BEFV infection could significantly up-regulate the miR-3470b expression in Baby Hamster Syrian Kidney cells (BHK-21) after 24 h and 48 h post-infection (pi) compared to normal BHK-21 cells without BEFV infection. Additionally, the target association between miR-3470b and mitochondrial antiviral signaling protein (MAVS) was predicted by target gene prediction tools and further validated using a dual-luciferase reporter assay, and the expression of MAVS mRNA and protein levels was negatively associated with miR-3470b levels. Furthermore, the miR-3470b mimic transfection significantly contributed to increase the BEFV N mRNA, G protein level and viral titer, respectively, whereas the miR-3470b inhibitor had the opposite effect on BEFV replication. Moreover, the overexpression of MAVS or silencing of miR-3470b by its inhibitors suppressed BEFV replication, and knockdown of MAVS by small interfering RNA also promoted the replication of BEFV.

CONCLUSIONS: Our findings is the first to reveal that miR-3470b as a novel host factor regulates BEFV replication via directly targeting the MAVS gene in BHK-21 cells and may provide a potential strategy for developing effective antiviral therapy.}, } @article {pmid30587112, year = {2018}, author = {Rezazadegan, R and Reidys, C}, title = {Degeneracy and genetic assimilation in RNA evolution.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {543}, doi = {10.1186/s12859-018-2497-3}, pmid = {30587112}, issn = {1471-2105}, mesh = {*Evolution, Molecular ; Humans ; Models, Genetic ; RNA/*chemistry ; }, abstract = {BACKGROUND: The neutral theory of Motoo Kimura stipulates that evolution is mostly driven by neutral mutations. However adaptive pressure eventually leads to changes in phenotype that involve non-neutral mutations. The relation between neutrality and adaptation has been studied in the context of RNA before and here we further study transitional mutations in the context of degenerate (plastic) RNA sequences and genetic assimilation. We propose quasineutral mutations, i.e. mutations which preserve an element of the phenotype set, as minimal mutations and study their properties. We also propose a general probabilistic interpretation of genetic assimilation and specialize it to the Boltzmann ensemble of RNA sequences.

RESULTS: We show that degenerate sequences i.e. sequences with more than one structure at the MFE level have the highest evolvability among all sequences and are central to evolutionary innovation. Degenerate sequences also tend to cluster together in the sequence space. The selective pressure in an evolutionary simulation causes the population to move towards regions with more degenerate sequences, i.e. regions at the intersection of different neutral networks, and this causes the number of such sequences to increase well beyond the average percentage of degenerate sequences in the sequence space. We also observe that evolution by quasineutral mutations tends to conserve the number of base pairs in structures and thereby maintains structural integrity even in the presence of pressure to the contrary.

CONCLUSIONS: We conclude that degenerate RNA sequences play a major role in evolutionary adaptation.}, } @article {pmid30587111, year = {2018}, author = {Szabó, R and Ferrier, DEK}, title = {Two more Posterior Hox genes and Hox cluster dispersal in echinoderms.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {203}, doi = {10.1186/s12862-018-1307-x}, pmid = {30587111}, issn = {1471-2148}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Hox genes are key elements in patterning animal development. They are renowned for their, often, clustered organisation in the genome, with supposed mechanistic links between the organisation of the genes and their expression. The widespread distribution and comparable functions of Hox genes across the animals has led to them being a major study system for comparing the molecular bases for construction and divergence of animal morphologies. Echinoderms (including sea urchins, sea stars, sea cucumbers, feather stars and brittle stars) possess one of the most unusual body plans in the animal kingdom with pronounced pentameral symmetry in the adults. Consequently, much interest has focused on their development, evolution and the role of the Hox genes in these processes. In this context, the organisation of echinoderm Hox gene clusters is distinctive. Within the classificatory system of Duboule, echinoderms constitute one of the clearest examples of Disorganized (D) clusters (i.e. intact clusters but with a gene order or orientation rearranged relative to the ancestral state).

RESULTS: Here we describe two Hox genes (Hox11/13d and e) that have been overlooked in most previous work and have not been considered in reconstructions of echinoderm Hox complements and cluster organisation. The two genes are related to Posterior Hox genes and are present in all classes of echinoderm. Importantly, they do not reside in the Hox cluster of any species for which genomic linkage data is available.

CONCLUSION: Incorporating the two neglected Posterior Hox genes into assessments of echinoderm Hox gene complements and organisation shows that these animals in fact have Split (S) Hox clusters rather than simply Disorganized (D) clusters within the Duboule classification scheme. This then has implications for how these genes are likely regulated, with them no longer covered by any potential long-range Hox cluster-wide, or multigenic sub-cluster, regulatory mechanisms.}, } @article {pmid30587110, year = {2018}, author = {Corona-Santiago, DK and Domínguez-Domínguez, O and Tovar-Mora, L and Pardos-Blas, JR and Herrerías-Diego, Y and Pérez-Rodríguez, R and Doadrio, I}, title = {Correction to: Historical biogeography reveals new independent evolutionary lineages in the Pantosteus plebeius-nebuliferus speciesgroup (Actinopterygii: Catostomidae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {206}, doi = {10.1186/s12862-018-1321-z}, pmid = {30587110}, issn = {1471-2148}, abstract = {Following publication of the original article.}, } @article {pmid30587109, year = {2018}, author = {Bonatto Paese, CL and Leite, DJ and Schönauer, A and McGregor, AP and Russell, S}, title = {Duplication and expression of Sox genes in spiders.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {205}, doi = {10.1186/s12862-018-1337-4}, pmid = {30587109}, issn = {1471-2148}, support = {BB/N007069/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: The Sox family of transcription factors is an important part of the genetic 'toolbox' of all metazoans examined to date and is known to play important developmental roles in vertebrates and insects. However, outside the commonly studied Drosophila model little is known about the repertoire of Sox family transcription factors in other arthropod species. Here we characterise the Sox family in two chelicerate species, the spiders Parasteatoda tepidariorum and Stegodyphus mimosarum, which have experienced a whole genome duplication (WGD) in their evolutionary history.

RESULTS: We find that virtually all of the duplicate Sox genes have been retained in these spiders after the WGD. Analysis of the expression of Sox genes in P. tepidariorum embryos suggests that it is likely that some of these genes have neofunctionalised after duplication. Our expression analysis also strengthens the view that an orthologue of vertebrate Group B1 genes, SoxNeuro, is implicated in the earliest events of CNS specification in both vertebrates and invertebrates. In addition, a gene in the Dichaete/Sox21b class is dynamically expressed in the spider segment addition zone, suggestive of an ancient regulatory mechanism controlling arthropod segmentation as recently suggested for flies and beetles. Together with the recent analysis of Sox gene expression in the embryos of other arthropods, our findings support the idea of conserved functions for some of these genes, including a potential role for SoxC and SoxD genes in CNS development and SoxF in limb development.

CONCLUSIONS: Our study provides a new chelicerate perspective to understanding the evolution and function of Sox genes and how the retention of duplicates of such important tool-box genes after WGD has contributed to different aspects of spider embryogenesis. Future characterisation of the function of these genes in spiders will help us to better understand the evolution of the regulation of important developmental processes in arthropods and other metazoans including neurogenesis and segmentation.}, } @article {pmid30587108, year = {2018}, author = {Giehr, J and Heinze, J}, title = {Queens stay, workers leave: caste-specific responses to fatal infections in an ant.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {202}, doi = {10.1186/s12862-018-1320-0}, pmid = {30587108}, issn = {1471-2148}, abstract = {BACKGROUND: The intense interactions among closely related individuals in animal societies provide perfect conditions for the spread of pathogens. Social insects have therefore evolved counter-measures on the cellular, individual, and social level to reduce the infection risk. One striking example is altruistic self-removal, i.e., lethally infected workers leave the nest and die in isolation to prevent the spread of a contagious disease to their nestmates. Because reproductive queens and egg-laying workers behave less altruistically than non-laying workers, e.g., when it comes to colony defense, we wondered whether moribund egg-layers would show the same self-removal as non-reproductive workers. Furthermore, we investigated how a lethal infection affects reproduction and studied if queens and egg-laying workers intensify their reproductive efforts when their residual reproductive value decreases ("terminal investment").

RESULTS: We treated queens, egg-laying workers from queenless colonies, and non-laying workers from queenright colonies of the monogynous (single-queened) ant Temnothorax crassispinus either with a control solution or a solution containing spores of the entomopathogenic fungus Metarhizium brunneum. Lethally infected workers left the nest and died away from it, regardless of their reproductive status. In contrast, infected queens never left the nest and were removed by workers only after they had died. The reproductive investment of queens strongly decreased after the treatment with both, the control solution and the Metarhizium brunneum suspension. The egg laying rate in queenless colonies was initially reduced in infected colonies but not in control colonies. Egg number increased again with decreasing number of infected workers.

CONCLUSIONS: Queens and workers of the ant Temnothorax crassispinus differ in their reaction to an infection risk and a reduced life expectancy. Workers isolate themselves to prevent contagion inside the colony, whereas queens stay in the nest. We did not find terminal investment; instead it appeared that egg-layers completely shut down egg production in response to the lethal infection. Workers in queenless colonies resumed reproduction only after all infected individuals had died, probably again to minimize the risk of infecting the offspring.}, } @article {pmid30587107, year = {2018}, author = {Zhao, D and Zheng, D}, title = {SMARTcleaner: identify and clean off-target signals in SMART ChIP-seq analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {544}, doi = {10.1186/s12859-018-2577-4}, pmid = {30587107}, issn = {1471-2105}, support = {R01 HL133120/HL/NHLBI NIH HHS/United States ; R01 MH099427/MH/NIMH NIH HHS/United States ; MH099427//National Institute of Mental Health/ ; HL133120//National Heart, Lung, and Blood Institute/ ; }, mesh = {Genomics/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Noises and artifacts may arise in several steps of the next-generation sequencing (NGS) process. Recently, an NGS library preparation method called SMART, or Switching Mechanism At the 5' end of the RNA Transcript, is introduced to prepare ChIP-seq (chromatin immunoprecipitation and deep sequencing) libraries from small amount of DNA material, using the DNA SMART ChIP-seq Kit. The protocol adds Ts to the 3' end of DNA templates, which is subsequently recognized and used by SMART poly(dA) primers for reverse transcription and then addition of PCR primers and sequencing adapters. The poly(dA) primers, however, can anneal to poly(T) sequences in a genome and amplify DNA fragments that are not enriched in the immunoprecipitated DNA templates. This off-target amplification results in false signals in the ChIP-seq data.

RESULTS: Here, we show that the off-target ChIP-seq reads derived from false amplification of poly(T/A) genomic sequences have unique and strand-specific features. Accordingly, we develop a tool (called "SMARTcleaner") that can exploit these features to remove SMART ChIP-seq artifacts. Application of SMARTcleaner to several SMART ChIP-seq datasets demonstrates that it can remove reads from off-target amplification effectively, leading to significantly improved ChIP-seq peaks and results.

CONCLUSIONS: SMARTcleaner could identify and clean the false signals in SMART-based ChIP-seq libraries, leading to improvement in peak calling, and downstream data analysis and interpretation.}, } @article {pmid30587106, year = {2018}, author = {Hwang, GH and Park, J and Lim, K and Kim, S and Yu, J and Yu, E and Kim, ST and Eils, R and Kim, JS and Bae, S}, title = {Web-based design and analysis tools for CRISPR base editing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {542}, doi = {10.1186/s12859-018-2585-4}, pmid = {30587106}, issn = {1471-2105}, mesh = {CRISPR-Cas Systems/*genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; Gene Editing/*methods ; Humans ; Internet/*instrumentation ; }, abstract = {BACKGROUND: As a result of its simplicity and high efficiency, the CRISPR-Cas system has been widely used as a genome editing tool. Recently, CRISPR base editors, which consist of deactivated Cas9 (dCas9) or Cas9 nickase (nCas9) linked with a cytidine or a guanine deaminase, have been developed. Base editing tools will be very useful for gene correction because they can produce highly specific DNA substitutions without the introduction of any donor DNA, but dedicated web-based tools to facilitate the use of such tools have not yet been developed.

RESULTS: We present two web tools for base editors, named BE-Designer and BE-Analyzer. BE-Designer provides all possible base editor target sequences in a given input DNA sequence with useful information including potential off-target sites. BE-Analyzer, a tool for assessing base editing outcomes from next generation sequencing (NGS) data, provides information about mutations in a table and interactive graphs. Furthermore, because the tool runs client-side, large amounts of targeted deep sequencing data (< 1 GB) do not need to be uploaded to a server, substantially reducing running time and increasing data security. BE-Designer and BE-Analyzer can be freely accessed at http://www.rgenome.net/be-designer/ and http://www.rgenome.net/be-analyzer /, respectively.

CONCLUSION: We develop two useful web tools to design target sequence (BE-Designer) and to analyze NGS data from experimental results (BE-Analyzer) for CRISPR base editors.}, } @article {pmid30587105, year = {2018}, author = {Kutch, IC and Fedorka, KM}, title = {Y-chromosomes can constrain adaptive evolution via epistatic interactions with other chromosomes.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {204}, doi = {10.1186/s12862-018-1327-6}, pmid = {30587105}, issn = {1471-2148}, abstract = {BACKGROUND: Variation in the non-coding regions of Y-chromosomes have been shown to influence gene regulation throughout the genome in some systems; a phenomenon termed Y-linked regulatory variation (YRV). This type of sex-specific genetic variance could have important implications for the evolution of male and female traits. If YRV contributes to the additive genetic variation of an autosomally coded trait shared between the sexes (e.g. body size), then selection could facilitate sexually dimorphic evolution via the Y-chromosome. In contrast, if YRV is entirely non-additive (i.e. interacts epistatically with other chromosomes), then Y-chromosomes could constrain trait evolution in both sexes whenever they are selected for the same trait value. The ability for this phenomenon to influence such fundamental evolutionary dynamics remains unexplored.

RESULTS: Here we address the evolutionary contribution of Y-linked variance by selecting for improved male geotaxis in populations possessing multiple Y-chromosomes (i.e. possessed Y-linked additive and/or epistatic variation) or a single Y-chromosome variant (i.e. possessed no Y-linked variation). We found that males from populations possessing Y-linked variation did not significantly respond to selection; however, males from populations with no Y-linked variation did respond. These patterns suggest the presence of a large quantity of Y-linked epistatic variance in the multi-Y population that dramatically slowed its response.

CONCLUSIONS: Our results imply that YRV is unlikely to facilitate the evolution of sexually dimorphic traits (at least for the trait examined here), but can interfere with the rate of trait evolution in both males and females. This result could have real biological implications as it suggests that YRV can affect how quickly a population responds to new selective pressures (e.g. invasive species, novel pathogens, or climate change). Considering that YRV influences hundreds of genes and is likely typical of other independently-evolved hemizygous chromosomes, YRV-like phenomena may represent common and significant costs to hemizygous sex determination.}, } @article {pmid30586650, year = {2018}, author = {Vicens, A and Vinuesa, P and Arenas, M and Treviño, CL}, title = {Analyzing the functional divergence of Slo1 and Slo3 channel subfamilies.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {33-41}, doi = {10.1016/j.ympev.2018.12.026}, pmid = {30586650}, issn = {1095-9513}, abstract = {Slo1 and Slo3 encode close paralogues of the Slo potassium (K+) channels family. Despite their evolutionary relatedness, Slo1 and Slo3 channels show marked functional differences and evolutionary dynamics. Whereas Slo1 is a highly conserved and widely expressed channel, Slo3 is a rapidly evolving channel restricted to sperm. However, the molecular mechanisms behind the structural-functional differences of Slo1 and Slo3 channels are unknown. In this study, we explored the functional divergence of Slo1 and Slo3 subfamilies in vertebrates and examined the structure-function relationships of our predictions using experimental data. We found that ∼25% of sites between Slo1 and Slo3 underwent altered functional constraints, affecting some residues with important roles in Slo1 channel gating. Because functional divergence was principally generated by accelerated evolution of Slo3 after gene duplication, we explored selective forces behind Slo3 diversification. We observed that Slo3 subjected was principally subjected to relaxation of purifying selection, but we also identified several sites evolving under positive selection in the cytosolic domain of this channel . Concerning Slo1, this channel presented strong purifying selection. Whether residues evolving under different selection in Slo1 and Slo3 are responsible for functional differences observed between these channels, as well as among Slo3 orthologs, remains to be established.}, } @article {pmid30586649, year = {2018}, author = {Bartáková, V and Bryja, J and Šanda, R and Bektas, Y and Stefanov, T and Choleva, L and Smith, C and Reichard, M}, title = {High cryptic diversity of bitterling fish in the southern West Palearctic.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {1-11}, doi = {10.1016/j.ympev.2018.12.025}, pmid = {30586649}, issn = {1095-9513}, abstract = {South-east Europe, along with the adjacent region of south-west Asia, is an important biodiversity hotspot with high local endemism largely contributed by contemporary continental lineages that retreated to southern refugia during colder Quaternary periods. We investigated the genetic diversity of the European bitterling fish (Rhodeus amarus) species complex (Cyprinidae) across its range in the western Palearctic, but with a particular emphasis in the region of Balkan, Pontic and Caspian refugia. We genotyped 12 polymorphic microsatellite loci and a partial sequence of mitochondrial gene cytochrome b (CYTB) for a set of 1,038 individuals from 60 populations. We used mtDNA sequences to infer phylogenetic relationships and historical demography, and microsatellite markers to describe fine-scale genetic variability and structure. Our mtDNA analysis revealed six well-supported lineages, with limited local co-occurrence. Two lineages are distributed throughout central and western Europe (lineages "A" and "B"), with two zones of secondary contact. Another two lineages were restricted to the Ponto-Aegean region of Greece (lineages "C" and "D") and the final two lineages were restricted south of the Caucasus mountains (lineage "E" from the Black Sea watershed and lineage "F" from the Caspian watershed). A signal of recent expansion was revealed in the two widespread lineages and the Ponto-Aegean lineage "C". The geographic distribution of clusters detected by nuclear microsatellites corresponded well with mitochondrial lineages and demonstrated finely sub-structured populations. A profound population structure suggested a significant role of genetic drift in differentiation among lineages. Lineage divergence in the Ponto-Aegean and Caspian regions are substantial, supporting the validity of two described endemic species (Rhodeus meridionalis as lineage "D" and Rhodeus colchicus as lineage "E") and invite taxonomic evaluation of the other two southern lineages (Thracean "C" and Caspian "F").}, } @article {pmid30585431, year = {2019}, author = {Sinha, P and Hochberg, NS}, title = {Crystal ball: the yesterday and tomorrow of tuberculosis.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {41-44}, doi = {10.1111/1758-2229.12726}, pmid = {30585431}, issn = {1758-2229}, } @article {pmid30585419, year = {2019}, author = {Santoro, AE}, title = {Crystal ball: the microbial map of the ocean.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {35-37}, doi = {10.1111/1758-2229.12721}, pmid = {30585419}, issn = {1758-2229}, } @article {pmid30585394, year = {2018}, author = {Spungin, D and Bidle, KD and Berman-Frank, I}, title = {Metacaspase involvement in programmed cell death of the marine cyanobacterium Trichodesmium.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14512}, pmid = {30585394}, issn = {1462-2920}, abstract = {Metacaspases are cysteine specific proteases implicated in cell-signalling, stress acclimation and programmed cell death (PCD) pathways in plants, fungi, protozoa, bacteria and algae. We investigated metacaspase-like gene expression and biochemical activity in the bloom-forming, N2 -fixing, marine cyanobacterium Trichodesmium, which undergoes PCD under low iron and high-light stress. We examined these patterns with respect to in-silico analyses of protein domain architectures that revealed a diverse array of regulatory domains within Trichodesmium metacaspases-like (TeMC) proteins. Experimental manipulations of laboratory cultures and oceanic surface blooms of Trichodesmium from the South Pacific Ocean triggered PCD under Fe-limitation and high light along with enhanced TeMC activity and upregulated expression of diverse TeMC representatives containing different regulatory domains. Furthermore, TeMC activity was significantly and positively correlated with caspase-like activity, which has been routinely observed to increase with PCD induction in Trichodesmium. Although both TeMC and caspase-like activities were stimulated upon PCD induction, inhibitor treatments of these proteolytic activities provided further evidence of largely distinct substrate specificities, even though some inhibitory crossover was observed. Our findings are the first results linking metacaspase expression and activity in PCD induced mortality in Trichodesmium. Yet, the role/s and specific activities of these different proteins remain to be elucidated.}, } @article {pmid30585387, year = {2018}, author = {Altinli, M and Soms, J and Ravallec, M and Justy, F and Bonneau, M and Weill, M and Gosselin-Grenet, AS and Sicard, M}, title = {Sharing cells with Wolbachia: the transovarian vertical transmission of Culex pipiens densovirus.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14511}, pmid = {30585387}, issn = {1462-2920}, support = {//Campus France/ ; //Ministère des affaires étrangères/ ; ANR-10-INBS-04//French National Research Agency/ ; }, abstract = {Culex pipiens densovirus (CpDV), a single stranded DNA virus, has been isolated from Culex pipiens mosquitoes but differs from other mosquito densoviruses in terms of genome structure and sequence identity. Its transmission from host to host, the nature of its interactions with both its host and host's endosymbiotic bacteria Wolbachia are not known. Here, we report the presence of CpDV in the ovaries and eggs of Cx. pipiens mosquitoes in close encounters with Wolbachia. In the ovaries, CpDV amount significantly differed between mosquito lines harbouring different strains of Wolbachia and these differences were not linked to variations in Wolbachia densities. CpDV was vertically transmitted in all laboratory lines to 17%-20% of the offspring. For some females, however, the vertical transmission reached 90%. Antibiotic treatment that cured the host from Wolbachia significantly decreased both CpDV quantity and vertical transmission suggesting an impact of host microbiota, including Wolbachia, on CpDV transmission. Overall our results show that CpDV is transmitted vertically via transovarian path along with Wolbachia with which it shares the same cells. Our results are primordial to understand the dynamics of densovirus infection, their persistence and spread in populations considering their potential use in the regulation of mosquito vector populations.}, } @article {pmid30585386, year = {2018}, author = {Cholet, F and Ijaz, UZ and Smith, CJ}, title = {Differential ratio amplicons (Ramp) for the evaluation of RNA integrity extracted from complex environmental samples.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14516}, pmid = {30585386}, issn = {1462-2920}, abstract = {Reliability and reproducibility of transcriptomics-based studies are dependent on RNA integrity. In microbial ecology, microfluidics-based techniques, such as the Ribosomal Integrity Number (RIN), targeting rRNA are currently the only approaches to evaluate RNA integrity. However, the relationship between rRNA and mRNA integrity is unknown. Here we present an integrity index, the Ratio Amplicon, Ramp , adapted from human clinical studies, to directly monitor mRNA integrity from complex environmental samples. We show, in a suite of experimental degradations of RNA extracted from sediment, that while the RIN generally reflected the degradation status of RNA the Ramp mapped mRNA degradation better. Furthermore, we examined the effect of degradation on transcript community structure by amplicon sequencing of 16S rRNA, amoA and glnA transcripts. We successfully sequenced transcripts for all three targets even from highly-degraded RNA samples. While RNA degradation changed the community structure of the mRNA profiles, no changes were observed for the 16S rRNA transcript profiles. Since both RT-Q-PCR and sequencing results were obtained, even from highly degraded samples, we strongly recommend evaluating RNA integrity prior to downstream processing to ensure meaningful results. For this both the RIN and Ramp are useful, with the Ramp better evaluating mRNA integrity in this study. This article is protected by copyright. All rights reserved.}, } @article {pmid30585382, year = {2018}, author = {Meier, DV and Pjevac, P and Bach, W and Markert, S and Schweder, T and Jamieson, J and Petersen, S and Amann, R and Meyerdierks, A}, title = {Microbial metal-sulfide oxidation in inactive hydrothermal vent chimneys suggested by metagenomic and metaproteomic analyses.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14514}, pmid = {30585382}, issn = {1462-2920}, support = {//Deutsche Forschungsgemeinschaft/ ; //Max-Planck-Gesellschaft/ ; //Max Planck Society/ ; SO216//German Research Foundation/ ; }, abstract = {Metal-sulfides are wide-spread in marine benthic habitats. At deep-sea hydrothermal vents, they occur as massive sulfide chimneys formed by mineral precipitation upon mixing of reduced vent fluids with cold oxygenated sea water. Although microorganisms inhabiting actively venting chimneys and utilizing compounds supplied by the venting fluids are well studied, only little is known about microorganisms inhabiting inactive chimneys. In this study, we combined 16S rRNA gene-based community profiling of sulfide chimneys from the Manus Basin (SW Pacific) with radiometric dating, metagenome (n = 4) and metaproteome (n = 1) analyses. Our results shed light on potential lifestyles of yet poorly characterized bacterial clades colonizing inactive chimneys. These include sulfate-reducing Nitrospirae and sulfide-oxidizing Gammaproteobacteria dominating most of the inactive chimney communities. Our phylogenetic analysis attributed the gammaproteobacterial clades to the recently described Woeseiaceae family and the SSr-clade found in marine sediments around the world. Metaproteomic data identified these Gammaproteobacteria as autotrophic sulfide-oxidizers potentially facilitating metal-sulfide dissolution via extracellular electron transfer. Considering the wide distribution of these gammaproteobacterial clades in marine environments such as hydrothermal vents and sediments, microbially accelerated neutrophilic mineral oxidation might be a globally relevant process in benthic element cycling and a considerable energy source for carbon fixation in marine benthic habitats.}, } @article {pmid30585380, year = {2018}, author = {Prajapati, D and Kumari, N and Dave, K and Chatupale, V and Pohnerkar, J}, title = {Chromomycin, an antibiotic produced by Streptomyces flaviscleroticus might play a role in the resistance to oxidative stress and is essential for viability in stationary phase.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14515}, pmid = {30585380}, issn = {1462-2920}, support = {80/844/2013/ECD-I//Indian Council of Medical Research/ ; }, abstract = {The well-known role of antibiotics in killing sensitive organisms has been challenged by the effects they exert at subinhibitory concentrations. Unfortunately, there are very few published reports on the advantages these molecules may confer to their producers. This study describes the construction of a genetically verified deletion mutant of Streptomyces flaviscleroticus unable to synthesize chromomycin. This mutant was characterized by a rapid loss of viability in stationary phase that was correlated with high oxidative stress and altered antioxidant defences. Altered levels of key metabolites in the mutant signalled a redistribution of the glycolytic flux toward the PPP to generate NADPH to fight oxidative stress as well as reduction of ATP-phosphofructokinase and Krebs cycle enzymes activities. These changes were correlated with a shift in the preference for carbon utilization from glucose to amino acids. Remarkably, chromomycin at subinhibitory concentration increased longevity of the non-producer and restored most of the phenotypic features' characteristic of the wild type strain. Altogether these observations suggest that chromomycin may have antioxidant properties that would explain, at least in part, some of the phenotypes of the mutant. Our observations warrant reconsideration of the secondary metabolite definition and raise the possibility of crucial roles for their producers.}, } @article {pmid30585375, year = {2018}, author = {Fang, X and Liu, Y and Zhao, Y and Chen, Y and Liu, R and Qin, QL and Li, G and Zhang, YZ and Chan, W and Hess, WR and Zeng, Q}, title = {Transcriptomic responses of the marine cyanobacterium Prochlorococcus to viral lysis products.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14513}, pmid = {30585375}, issn = {1462-2920}, support = {41776132//National Natural Science Foundation of China/ ; 91851112//National Natural Science Foundation of China/ ; U1706207//National Natural Science Foundation of China/ ; 31630012//National Natural Science Foundation of China/ ; 16102317//Research Grants Council, University Grants Committee/ ; 16102317//Research Grants Council of the Hong Kong Special Administrative Region, China/ ; }, abstract = {Viral infection of marine phytoplankton releases a variety of dissolved organic matter (DOM). The impact of viral DOM (vDOM) on the uninfected co-occurring phytoplankton remains largely unknown. Here, we conducted transcriptomic analyses to study the effects of vDOM on the cyanobacterium Prochlorococcus, which is the most abundant photosynthetic organism on Earth. Using Prochlorococcus MIT9313, we showed that its growth was not affected by vDOM, but many tRNAs increased in abundance. We tested tRNA-gly and found that its abundance increased upon addition of glycine. The decreased transcript abundances of N metabolism genes also suggested that Prochlorococcus responded to organic N compounds in vDOM. Addition of vDOM to Prochlorococcus reduced the maximum photochemical efficiency of photosystem II and CO2 fixation while increasing its respiration rate, consistent with differentially abundant transcripts related to photosynthesis and respiration. One of the highest positive fold-changes was observed for the 6S RNA, a noncoding RNA functioning as a global transcriptional regulator in bacteria. The high level of 6S RNA might be responsible for some of the observed transcriptional responses. Taken together, our results revealed the transcriptional regulation of Prochlorococcus in response to viral lysis products and suggested its metabolic potential to utilize organic N compounds.}, } @article {pmid30584919, year = {2018}, author = {Thode, VA and Sanmartín, I and Lohmann, LG}, title = {Contrasting patterns of diversification between Amazonian and Atlantic forest clades of Neotropical lianas (Amphilophium, Bignonieae) inferred from plastid genomic data.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {92-106}, doi = {10.1016/j.ympev.2018.12.021}, pmid = {30584919}, issn = {1095-9513}, abstract = {The mechanisms and processes underlying patterns of species distributions have intrigued ecologists and biogeographers for a long time. The Neotropics is the most species-rich region in the World, representing an excellent model for studying the drivers of diversification. In this study, we used a phylogenomic approach to infer relationships and examine the role of major geological and climatic events in shaping biogeographic patterns within Amphilophium (Bignonieae, Bignoniaceae), a genus of Neotropical lianas. Even though Amphilophium is broadly distributed across the Neotropics, it is centered in Amazonia and the Atlantic rainforest. We generated nearly-complete plastome sequences for 32 species of Amphilophium, representing 70% of the species diversity in the genus. The final dataset included 78 plastid-coding regions and was analyzed under Maximum Likelihood and Bayesian approaches to reconstruct the phylogeny of Amphilophium. We also used this dataset to estimate divergence times using a Bayesian relaxed-clock approach. We further inferred ancestral ranges, migration events, and shifts in diversification rates using a branch-specific diversification model and the Dispersal-Extinction-Cladogenesis (DEC) model implemented in a Bayesian phylogenetic framework. Overall, we obtained a well-resolved and strongly supported phylogeny for Amphilophium, with five main clades that are well characterized by morphological features. Amphilophium originated in the Early Oligocene, and started to diversify in the Late Oligocene. The first diversification event involved a split between Amazonian and Atlantic forest clades. These two clades showed very different diversification scenarios. Divergence within the Atlantic forest clade began in the Mid-Oligocene, while the Amazonian clade underwent rapid diversification starting in the Late Miocene. In-situ speciation characterized the Amazonian clade, whereas allopatric speciation driven by migration events into other Neotropical biomes were mostly inferred within the Atlantic forest clade. The diversification of Amphilophium in the Neotropics was triggered by major geological events and changes in landscape that occurred during the Late Paleogene and Neogene, with little influence of the climatic changes of the Pleistocene ice ages. The divergence times and range inferences support the role of the Western Amazonian "megawetlands" and the formation of the South American "dry diagonal" as key climatic and geological barriers that separated the Atlantic forest from the Amazonian lowlands. Timing of migration events agrees with a Mid-Miocene closure of the Central American Seaway.}, } @article {pmid30584918, year = {2018}, author = {Lavin, BR and Girman, DJ}, title = {Phylogenetic relationships and divergence dating in the Glass Lizards (Anguinae).}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {128-140}, doi = {10.1016/j.ympev.2018.12.022}, pmid = {30584918}, issn = {1095-9513}, abstract = {The Glass Lizards are a subfamily (Anguinae) of Anguid Lizards with an elongated limbless body plan that occur throughout the Northern Hemisphere primarily in North America, Europe, and Asia, but also have a presence in North Africa and Indonesia. We used twenty-five nuclear loci (15,191 bp) and 2090 bp of the mtDNA genome to generate a phylogeny containing all known species groups to explore species relationships within the group as well as divergence dating. We also examined the group in the context of a coalescent species tree analysis and species delimitation. All major lineages were found to be monophyletic with potential cryptic diversity in some. The Anguinae first appeared in the Eocene and most lineages were present by the beginning of the Miocene. The Anguinae originated in Europe from an Anguidae ancestor that crossed the Thulean land bridge, spreading to Asia after the drying of the Turgai Sea, then across Beringia as the climate permitted. A species tree analyses found support for the major Anguinae lineages and species delimitation supported accepted species.}, } @article {pmid30584917, year = {2018}, author = {Stireman, JO and Cerretti, P and O'Hara, JE and Blaschke, JD and Moulton, JK}, title = {Molecular phylogeny and evolution of world Tachinidae (Diptera).}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ympev.2018.12.002}, pmid = {30584917}, issn = {1095-9513}, abstract = {We reconstructed phylogenetic relationships within the diverse parasitoid fly family Tachinidae using four nuclear loci (7800 bp) and including an exceptionally large sample of more than 500 taxa from around the world. The position of the earthworm-parasitizing Polleniinae (Calliphoridae s.l.) as sister to Tachinidae is strongly supported. Our analyses recovered each of the four tachinid subfamilies and most recognized tribes, with some important exceptions in the Dexiinae and Tachininae. Most notably, the tachinine tribes Macquartiini and Myiophasiini form a clade sister to all other Tachinidae, and a clade of Palpostomatini is reconstructed as sister to Dexiinae + Phasiinae. Although most nodes are well-supported, relationships within several lineages that appear to have undergone rapid episodes of diversification (basal Dexiinae and Tachininae, Blondeliini) were poorly resolved. Reconstructions of host use evolution are equivocal, but generally support the hypothesis that the ancestral host of tachinids was a beetle and that subsequent host shifts to caterpillars may coincide with accelerated diversification. Evolutionary reconstructions of reproductive strategy using alternative methods were incongruent, however it is most likely that ancestral tachinids possessed unincubated, thick shelled eggs from which incubated eggs evolved repeatedly, potentially expanding available host niches. These results provide a broad foundation for understanding the phylogeny and evolution of this important family of parasitoid insects. We hope it will serve as a framework to be used in concert with morphology and other sources of evidence to revise the higher taxonomic classification of Tachinidae and further explore their evolutionary history and diversification.}, } @article {pmid30584112, year = {2019}, author = {Liao, ML and Somero, GN and Dong, YW}, title = {Comparing mutagenesis and simulations as tools for identifying functionally important sequence changes for protein thermal adaptation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {679-688}, doi = {10.1073/pnas.1817455116}, pmid = {30584112}, issn = {1091-6490}, abstract = {Comparative studies of orthologous proteins of species evolved at different temperatures have revealed consistent patterns of temperature-related variation in thermal stabilities of structure and function. However, the precise mechanisms by which interspecific variations in sequence foster these adaptive changes remain largely unknown. Here, we compare orthologs of cytosolic malate dehydrogenase (cMDH) from marine molluscs adapted to temperatures ranging from -1.9 °C (Antarctica) to ∼55 °C (South China coast) and show how amino acid usage in different regions of the enzyme (surface, intermediate depth, and protein core) varies with adaptation temperature. This eukaryotic enzyme follows some but not all of the rules established in comparisons of archaeal and bacterial proteins. To link the effects of specific amino acid substitutions with adaptive variations in enzyme thermal stability, we combined site-directed mutagenesis (SDM) and in vitro protein experimentation with in silico mutagenesis using molecular dynamics simulation (MDS) techniques. SDM and MDS methods generally but not invariably yielded common effects on protein stability. MDS analysis is shown to provide insights into how specific amino acid substitutions affect the conformational flexibilities of mobile regions (MRs) of the enzyme that are essential for binding and catalysis. Whereas these substitutions invariably lie outside of the MRs, they effectively transmit their flexibility-modulating effects to the MRs through linked interactions among surface residues. This discovery illustrates that regions of the protein surface lying outside of the site of catalysis can help establish an enzyme's thermal responses and foster evolutionary adaptation of function.}, } @article {pmid30584111, year = {2019}, author = {Carolin, SA and Walker, RT and Day, CC and Ersek, V and Sloan, RA and Dee, MW and Talebian, M and Henderson, GM}, title = {Precise timing of abrupt increase in dust activity in the Middle East coincident with 4.2 ka social change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {67-72}, doi = {10.1073/pnas.1808103115}, pmid = {30584111}, issn = {1091-6490}, abstract = {The extent to which climate change causes significant societal disruption remains controversial. An important example is the decline of the Akkadian Empire in northern Mesopotamia ∼4.2 ka, for which the existence of a coincident climate event is still uncertain. Here we present an Iranian stalagmite record spanning 5.2 ka to 3.7 ka, dated with 25 U/Th ages that provide an average age uncertainty of 31 y (1σ). We find two periods of increased Mg/Ca, beginning abruptly at 4.51 and 4.26 ka, and lasting 110 and 290 y, respectively. Each of these periods coincides with slower vertical stalagmite growth and a gradual increase in stable oxygen isotope ratios. The periods of high Mg/Ca are explained by periods of increased dust flux sourced from the Mesopotamia region, and the abrupt onset of this dustiness indicates threshold behavior in response to aridity. This interpretation is consistent with existing marine and terrestrial records from the broad region, which also suggest that the later, longer event beginning at 4.26 ka is of greater regional extent and/or amplitude. The chronological precision and high resolution of our record indicates that there is no significant difference, at decadal level, between the start date of the second, larger dust event and the timing of North Mesopotamia settlement abandonment, and furthermore reveals striking similarity between the total duration of the second dust event and settlement abandonment. The Iranian record demonstrates this region's threshold behavior in dust production, and its ability to maintain this climate state for multiple centuries naturally.}, } @article {pmid30584110, year = {2019}, author = {McDougall, R and Kristiansen, P and Rader, R}, title = {Small-scale urban agriculture results in high yields but requires judicious management of inputs to achieve sustainability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {129-134}, doi = {10.1073/pnas.1809707115}, pmid = {30584110}, issn = {1091-6490}, abstract = {A major challenge of the 21st century is to produce more food for a growing population without increasing humanity's agricultural footprint. Urban food production may help to solve this challenge; however, little research has examined the productivity of urban farming systems. We investigated inputs and produce yields over a 1-y period in 13 small-scale organic farms and gardens in Sydney, Australia. We found mean yields to be 5.94 kg⋅m-2, around twice the yield of typical Australian commercial vegetable farms. While these systems used land efficiently, economic and emergy (embodied energy) analyses showed they were relatively inefficient in their use of material and labor resources. Benefit-to-cost ratios demonstrated that, on average, the gardens ran at a financial loss and emergy transformity was one to three orders of magnitude greater than many conventional rural farms. Only 14.66% of all inputs were considered "renewable," resulting in a moderate mean environmental loading ratio (ELR) of 5.82, a value within the range of many conventional farming systems. However, when all nonrenewable inputs capable of being substituted with local renewable inputs were replaced in a hypothetical scenario, the ELR improved markedly to 1.32. These results show that urban agriculture can be highly productive; however, this productivity comes with many trade-offs, and care must be taken to ensure its sustainability.}, } @article {pmid30584109, year = {2019}, author = {van Dorp, L and Lowes, S and Weigel, JL and Ansari-Pour, N and López, S and Mendoza-Revilla, J and Robinson, JA and Henrich, J and Thomas, MG and Nunn, N and Hellenthal, G}, title = {Genetic legacy of state centralization in the Kuba Kingdom of the Democratic Republic of the Congo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {593-598}, doi = {10.1073/pnas.1811211115}, pmid = {30584109}, issn = {1091-6490}, abstract = {Few phenomena have had as profound or long-lasting consequences in human history as the emergence of large-scale centralized states in the place of smaller scale and more local societies. This study examines a fundamental, and yet unexplored, consequence of state formation: its genetic legacy. We studied the genetic impact of state centralization during the formation of the eminent precolonial Kuba Kingdom of the Democratic Republic of the Congo (DRC) in the 17th century. We analyzed genome-wide data from over 690 individuals sampled from 27 different ethnic groups from the Kasai Central Province of the DRC. By comparing genetic patterns in the present-day Kuba, whose ancestors were part of the Kuba Kingdom, with those in neighboring non-Kuba groups, we show that the Kuba today are more genetically diverse and more similar to other groups in the region than expected, consistent with the historical unification of distinct subgroups during state centralization. We also found evidence of genetic mixing dating to the time of the Kingdom at its most prominent. Using this unique dataset, we characterize the genetic history of the Kasai Central Province and describe the historic late wave of migrations into the region that contributed to a Bantu-like ancestry component found across large parts of Africa today. Taken together, we show the power of genetics to evidence events of sociopolitical importance and highlight how DNA can be used to better understand the behaviors of both people and institutions in the past.}, } @article {pmid30584108, year = {2019}, author = {}, title = {Correction for Smith et al., Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {337}, doi = {10.1073/pnas.1819306115}, pmid = {30584108}, issn = {1091-6490}, } @article {pmid30584107, year = {2019}, author = {Li, Y and Pizer, WA and Wu, L}, title = {Climate change and residential electricity consumption in the Yangtze River Delta, China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {472-477}, doi = {10.1073/pnas.1804667115}, pmid = {30584107}, issn = {1091-6490}, abstract = {Estimating the impact of climate change on energy use across the globe is essential for analysis of both mitigation and adaptation policies. Yet existing empirical estimates are concentrated in Western countries, especially the United States. We use daily data on household electricity consumption to estimate how electricity consumption would change in Shanghai in the context of climate change. For colder days <7 °C, a 1 °C increase in daily temperature reduces electricity consumption by 2.8%. On warm days >25 °C, a 1 °C increase in daily temperatures leads to a 14.5% increase in electricity consumption. As income increases, households' weather sensitivity remains the same for hotter days in the summer but increases during the winter. We use this estimated behavior in conjunction with a collection of downscaled global climate models (GCMs) to construct a relationship between future annual global mean surface temperature (GMST) changes and annual residential electricity consumption. We find that annual electricity consumption increases by 9.2% per +1 °C in annual GMST. In comparison, annual peak electricity use increases by as much as 36.1% per +1 °C in annual GMST. Although most accurate for Shanghai, our findings could be most credibly extended to the urban areas in the Yangtze River Delta, covering roughly one-fifth of China's urban population and one-fourth of the gross domestic product.}, } @article {pmid30584106, year = {2019}, author = {Azose, JJ and Raftery, AE}, title = {Estimation of emigration, return migration, and transit migration between all pairs of countries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {116-122}, doi = {10.1073/pnas.1722334116}, pmid = {30584106}, issn = {1091-6490}, abstract = {We propose a method for estimating migration flows between all pairs of countries that allows for decomposition of migration into emigration, return, and transit components. Current state-of-the-art estimates of bilateral migration flows rely on the assumption that the number of global migrants is as small as possible. We relax this assumption, producing complete estimates of all between-country migration flows with genuine estimates of total global migration. We find that the total number of individuals migrating internationally has oscillated between 1.13 and 1.29% of the global population per 5-year period since 1990. Return migration and transit migration are big parts of total migration; roughly one of four migration events is a return to an individual's country of birth. In the most recent time period, we estimate particularly large return migration flows from the United States to Central and South America and from the Persian Gulf to south Asia.}, } @article {pmid30584105, year = {2019}, author = {Irieda, H and Inoue, Y and Mori, M and Yamada, K and Oshikawa, Y and Saitoh, H and Uemura, A and Terauchi, R and Kitakura, S and Kosaka, A and Singkaravanit-Ogawa, S and Takano, Y}, title = {Conserved fungal effector suppresses PAMP-triggered immunity by targeting plant immune kinases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {496-505}, doi = {10.1073/pnas.1807297116}, pmid = {30584105}, issn = {1091-6490}, abstract = {Plant pathogens have optimized their own effector sets to adapt to their hosts. However, certain effectors, regarded as core effectors, are conserved among various pathogens, and may therefore play an important and common role in pathogen virulence. We report here that the widely distributed fungal effector NIS1 targets host immune components that transmit signaling from pattern recognition receptors (PRRs) in plants. NIS1 from two Colletotrichum spp. suppressed the hypersensitive response and oxidative burst, both of which are induced by pathogen-derived molecules, in Nicotiana benthamianaMagnaporthe oryzae NIS1 also suppressed the two defense responses, although this pathogen likely acquired the NIS1 gene via horizontal transfer from Basidiomycota. Interestingly, the root endophyte Colletotrichum tofieldiae also possesses a NIS1 homolog that can suppress the oxidative burst in N. benthamiana We show that NIS1 of multiple pathogens commonly interacts with the PRR-associated kinases BAK1 and BIK1, thereby inhibiting their kinase activities and the BIK1-NADPH oxidase interaction. Furthermore, mutations in the NIS1-targeting proteins, i.e., BAK1 and BIK1, in Arabidopsis thaliana also resulted in reduced immunity to Colletotrichum fungi. Finally, M. oryzae lacking NIS1 displayed significantly reduced virulence on rice and barley, its hosts. Our study therefore reveals that a broad range of filamentous fungi maintain and utilize the core effector NIS1 to establish infection in their host plants and perhaps also beneficial interactions, by targeting conserved and central PRR-associated kinases that are also known to be targeted by bacterial effectors.}, } @article {pmid30584104, year = {2019}, author = {Baranov, SV and Baranova, OV and Yablonska, S and Suofu, Y and Vazquez, AL and Kozai, TDY and Cui, XT and Ferrando, LM and Larkin, TM and Tyurina, YY and Kagan, VE and Carlisle, DL and Kristal, BS and Friedlander, RM}, title = {Mitochondria modulate programmed neuritic retraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {650-659}, doi = {10.1073/pnas.1811021116}, pmid = {30584104}, issn = {1091-6490}, support = {R01 NS094404/NS/NINDS NIH HHS/United States ; }, abstract = {Neuritic retraction in the absence of overt neuronal death is a shared feature of normal aging and neurodegenerative disorders, but the intracellular mechanisms modulating this process are not understood. We propose that cumulative distal mitochondrial protein damage results in impaired protein import, leading to mitochondrial dysfunction and focal activation of the canonical apoptosis pathway in neurites. This is a controlled process that may not lead to neuronal death and, thus, we term this phenomenon "neuritosis." Consistent with our hypothesis, we show that in primary cerebrocortical neurons, mitochondrial distance from the soma correlates with increased mitochondrial protein damage, PINK1 accumulation, reactive oxygen species production, and decreased mitochondrial membrane potential and depolarization threshold. Furthermore, we demonstrate that the distance-dependent mitochondrial membrane potential gradient exists in vivo in mice. We demonstrate that impaired distal mitochondria have a lower threshold for focal/nonlethal neuritic caspase-3 activation in normal neurons that is exacerbated in aging, stress, and neurodegenerative conditions, thus delineating a fundamental mechanistic underpinning for synaptic vulnerability.}, } @article {pmid30584103, year = {2019}, author = {Lyu, Q and Xu, S and Lyu, Y and Choi, M and Christie, CK and Slivano, OJ and Rahman, A and Jin, ZG and Long, X and Xu, Y and Miano, JM}, title = {SENCR stabilizes vascular endothelial cell adherens junctions through interaction with CKAP4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {546-555}, doi = {10.1073/pnas.1810729116}, pmid = {30584103}, issn = {1091-6490}, abstract = {SENCR is a human-specific, vascular cell-enriched long-noncoding RNA (lncRNA) that regulates vascular smooth muscle cell and endothelial cell (EC) phenotypes. The underlying mechanisms of action of SENCR in these and other cell types is unknown. Here, levels of SENCR RNA are shown to be elevated in several differentiated human EC lineages subjected to laminar shear stress. Increases in SENCR RNA are also observed in the laminar shear stress region of the adult aorta of humanized SENCR-expressing mice, but not in disturbed shear stress regions. SENCR loss-of-function studies disclose perturbations in EC membrane integrity resulting in increased EC permeability. Biotinylated RNA pull-down and mass spectrometry establish an abundant SENCR-binding protein, cytoskeletal-associated protein 4 (CKAP4); this ribonucleoprotein complex was further confirmed in an RNA immunoprecipitation experiment using an antibody to CKAP4. Structure-function studies demonstrate a noncanonical RNA-binding domain in CKAP4 that binds SENCR Upon SENCR knockdown, increasing levels of CKAP4 protein are detected in the EC surface fraction. Furthermore, an interaction between CKAP4 and CDH5 is enhanced in SENCR-depleted EC. This heightened association appears to destabilize the CDH5/CTNND1 complex and augment CDH5 internalization, resulting in impaired adherens junctions. These findings support SENCR as a flow-responsive lncRNA that promotes EC adherens junction integrity through physical association with CKAP4, thereby stabilizing cell membrane-bound CDH5.}, } @article {pmid30584102, year = {2019}, author = {Xiao, B and Yin, S and Hu, Y and Sun, M and Wei, J and Huang, Z and Wen, Y and Dai, X and Chen, H and Mu, J and Cui, L and Jiang, L}, title = {Epigenetic editing by CRISPR/dCas9 in Plasmodium falciparum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {255-260}, doi = {10.1073/pnas.1813542116}, pmid = {30584102}, issn = {1091-6490}, support = {R01 AI116466/AI/NIAID NIH HHS/United States ; U19 AI089672/AI/NIAID NIH HHS/United States ; }, abstract = {Genetic manipulation remains a major obstacle for understanding the functional genomics of the deadliest malaria parasite Plasmodium falciparum Although the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeat/CRISPR-associated protein 9) system has been successfully applied to introduce permanent changes in the parasite genome, its use is still limited. Here we show that fusing different epigenetic effector domains to a Cas9 null mutant efficiently and specifically reprograms the expression of target genes in P. falciparum By precisely writing and erasing histone acetylation at the transcription start site regions of the invasion-related genes reticulocyte binding protein homolog 4 (rh4) and erythrocyte binding protein 175 (eba-175), respectively, we achieved significant activation of rh4 and repression of eba-175, leading to the switch of the parasite invasion pathways into human erythrocytes. By using the epigenetic knockdown system, we have also characterized the effects of PfSET1, previously identified as an essential gene, on expression of mainly trophozoite- and schizont-specific genes, and therefore regulation of the growth of the mature forms of P. falciparum This epigenetic CRISPR/dCas9 system provides a powerful approach for regulating gene expression at the transcriptional level in P. falciparum.}, } @article {pmid30584101, year = {2019}, author = {Voiniciuc, C and Dama, M and Gawenda, N and Stritt, F and Pauly, M}, title = {Mechanistic insights from plant heteromannan synthesis in yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {522-527}, doi = {10.1073/pnas.1814003116}, pmid = {30584101}, issn = {1091-6490}, abstract = {Heteromannan (HM) is one of the most ancient cell wall polymers in the plant kingdom, consisting of β-(1-4)-linked backbones of glucose (Glc) and mannose (Man) units. Despite the widespread distribution of HM polysaccharides, their biosynthesis remains mechanistically unclear. HM is elongated by glycosyltransferases (GTs) from the cellulose synthase-like A (CSLA) family. MANNAN-SYNTHESIS RELATED (MSR) putative GTs have also been implicated in (gluco)mannan synthesis, but their roles have been difficult to decipher in planta and in vitro. To further characterize the products of the HM synthases and accessory proteins, we chose a synthetic biology approach to synthesize plant HM in yeast. The expression of a CSLA protein in Pichia pastoris led to the abundant production of plant HM: up to 30% of glycans in the yeast cell wall. Based on sequential chemical and enzymatic extractions, followed by detailed structural analyses, the newly produced HM polymers were unbranched and could be larger than 270 kDa. Using CSLAs from different species, we programmed yeast cells to produce an HM backbone composed exclusively of Man or also incorporating Glc. We demonstrate that specific MSR cofactors were indispensable for mannan synthase activity of a coffee CSLA or modulated a functional CSLA enzyme to produce glucomannan instead of mannan. Therefore, this powerful platform yields functional insight into the molecular machinery required for HM biosynthesis in plants.}, } @article {pmid30584100, year = {2019}, author = {Levi, T and Barfield, M and Barrantes, S and Sullivan, C and Holt, RD and Terborgh, J}, title = {Tropical forests can maintain hyperdiversity because of enemies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {581-586}, doi = {10.1073/pnas.1813211116}, pmid = {30584100}, issn = {1091-6490}, abstract = {Explaining the maintenance of tropical forest diversity under the countervailing forces of drift and competition poses a major challenge to ecological theory. Janzen-Connell effects, in which host-specific natural enemies restrict the recruitment of juveniles near conspecific adults, provide a potential mechanism. Janzen-Connell is strongly supported empirically, but existing theory does not address the stable coexistence of hundreds of species. Here we use high-performance computing and analytical models to demonstrate that tropical forest diversity can be maintained nearly indefinitely in a prolonged state of transient dynamics due to distance-responsive natural enemies. Further, we show that Janzen-Connell effects lead to community regulation of diversity by imposing a diversity-dependent cost to commonness and benefit to rarity. The resulting species-area and rank-abundance relationships are consistent with empirical results. Diversity maintenance over long time spans does not require dispersal from an external metacommunity, speciation, or resource niche partitioning, only a small zone around conspecific adults in which saplings fail to recruit. We conclude that the Janzen-Connell mechanism can explain the maintenance of tropical tree diversity while not precluding the operation of other niche-based mechanisms such as resource partitioning.}, } @article {pmid30584099, year = {2019}, author = {Stadtfeld, C and Vörös, A and Elmer, T and Boda, Z and Raabe, IJ}, title = {Integration in emerging social networks explains academic failure and success.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {792-797}, doi = {10.1073/pnas.1811388115}, pmid = {30584099}, issn = {1091-6490}, abstract = {Academic success of students has been explained with a variety of individual and socioeconomic factors. Social networks that informally emerge within student communities can have an additional effect on their achievement. However, this effect of social ties is difficult to measure and quantify, because social networks are multidimensional and dynamically evolving within the educational context. We repeatedly surveyed a cohort of 226 engineering undergraduates between their first day at university and a crucial examination at the end of the academic year. We investigate how social networks emerge between previously unacquainted students and how integration in these networks explains academic success. Our study measures multiple important dimensions of social ties between students: their positive interactions, friendships, and studying relations. By using statistical models for dynamic network data, we are able to investigate the processes of social network formation in the cohort. We find that friendship ties informally evolve into studying relationships over the academic year. This process is crucial, as studying together with others, in turn, has a strong impact on students' success at the examination. The results are robust to individual differences in socioeconomic background factors and to various indirect measures of cognitive abilities, such as prior academic achievement and being perceived as smart by other students. The findings underline the importance of understanding social network dynamics in educational settings. They call for the creation of university environments promoting the development of positive relationships in pursuit of academic success.}, } @article {pmid30584098, year = {2019}, author = {Ye, L and Rouxel, JR and Cho, D and Mukamel, S}, title = {Imaging electron-density fluctuations by multidimensional X-ray photon-coincidence diffraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {395-400}, doi = {10.1073/pnas.1816730116}, pmid = {30584098}, issn = {1091-6490}, abstract = {The ultrafast spontaneous electron-density fluctuation dynamics in molecules is studied theoretically by off-resonant multiple X-ray diffraction events. The time- and wavevector-resolved photon-coincidence signals give an image of electron-density fluctuations expressed through the four-point correlation function of the charge density in momentum space. A Fourier transform of the signal provides a real-space image of the multipoint charge-density correlation functions, which reveal snapshots of the evolving electron density in between the diffraction events. The proposed technique is illustrated by ab initio simulations of the momentum- and real-space inelastic scattering signals from a linear cyanotetracetylene molecule.}, } @article {pmid30584097, year = {2019}, author = {}, title = {Correction for Namouchi et al., Integrative approach using Yersinia pestis genomes to revisit the historical landscape of plague during the Medieval Period.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {338}, doi = {10.1073/pnas.1820659116}, pmid = {30584097}, issn = {1091-6490}, } @article {pmid30584096, year = {2019}, author = {Chatzivasileiou, AO and Ward, V and Edgar, SM and Stephanopoulos, G}, title = {Two-step pathway for isoprenoid synthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {506-511}, doi = {10.1073/pnas.1812935116}, pmid = {30584096}, issn = {1091-6490}, abstract = {Isoprenoids comprise a large class of chemicals of significant interest due to their diverse properties. Biological production of isoprenoids is considered to be the most efficient way for their large-scale production. Isoprenoid biosynthesis has thus far been dependent on pathways inextricably linked to glucose metabolism. These pathways suffer from inherent limitations due to their length, complex regulation, and extensive cofactor requirements. Here, we present a synthetic isoprenoid pathway that aims to overcome these limitations. This isopentenol utilization pathway (IUP) can produce isopentenyl diphosphate or dimethylallyl diphosphate, the main precursors to isoprenoid synthesis, through sequential phosphorylation of isopentenol isomers isoprenol or prenol. After identifying suitable enzymes and constructing the pathway, we attempted to probe the limits of the IUP for producing various isoprenoid downstream products. The IUP flux exceeded the capacity of almost all downstream pathways tested and was competitive with the highest isoprenoid fluxes reported.}, } @article {pmid30584095, year = {2019}, author = {Huang, R and Ripstein, ZA and Rubinstein, JL and Kay, LE}, title = {Cooperative subunit dynamics modulate p97 function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {158-167}, doi = {10.1073/pnas.1815495116}, pmid = {30584095}, issn = {1091-6490}, abstract = {p97 is an essential hexameric AAA+ ATPase involved in a wide range of cellular processes. Mutations in the enzyme are implicated in the etiology of an autosomal dominant neurological disease in which patients are heterozygous with respect to p97 alleles, containing one copy each of WT and disease-causing mutant genes, so that, in vivo, p97 molecules can be heterogeneous in subunit composition. Studies of p97 have, however, focused on homohexameric constructs, where protomers are either entirely WT or contain a disease-causing mutation, showing that for WT p97, the N-terminal domain (NTD) of each subunit can exist in either a down (ADP) or up (ATP) conformation. NMR studies establish that, in the ADP-bound state, the up/down NTD equilibrium shifts progressively toward the up conformation as a function of disease mutant severity. To understand NTD functional dynamics in biologically relevant p97 heterohexamers comprising both WT and disease-causing mutant subunits, we performed a methyl-transverse relaxation optimized spectroscopy (TROSY) NMR study on a series of constructs in which only one of the protomer types is NMR-labeled. Our results show positive cooperativity of NTD up/down equilibria between neighboring protomers, allowing us to define interprotomer pathways that mediate the allosteric communication between subunits. Notably, the perturbed up/down NTD equilibrium in mutant subunits is partially restored by neighboring WT protomers, as is the two-pronged binding of the UBXD1 adaptor that is affected in disease. This work highlights the plasticity of p97 and how subtle perturbations to its free-energy landscape lead to significant changes in NTD conformation and adaptor binding.}, } @article {pmid30584094, year = {2019}, author = {Kahiluoto, H and Kaseva, J and Balek, J and Olesen, JE and Ruiz-Ramos, M and Gobin, A and Kersebaum, KC and Takáč, J and Ruget, F and Ferrise, R and Bezak, P and Capellades, G and Dibari, C and Mäkinen, H and Nendel, C and Ventrella, D and Rodríguez, A and Bindi, M and Trnka, M}, title = {Decline in climate resilience of European wheat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {123-128}, doi = {10.1073/pnas.1804387115}, pmid = {30584094}, issn = {1091-6490}, abstract = {Food security relies on the resilience of staple food crops to climatic variability and extremes, but the climate resilience of European wheat is unknown. A diversity of responses to disturbance is considered a key determinant of resilience. The capacity of a sole crop genotype to perform well under climatic variability is limited; therefore, a set of cultivars with diverse responses to weather conditions critical to crop yield is required. Here, we show a decline in the response diversity of wheat in farmers' fields in most European countries after 2002-2009 based on 101,000 cultivar yield observations. Similar responses to weather were identified in cultivar trials among central European countries and southern European countries. A response diversity hotspot appeared in the trials in Slovakia, while response diversity "deserts" were identified in Czechia and Germany and for durum wheat in southern Europe. Positive responses to abundant precipitation were lacking. This assessment suggests that current breeding programs and cultivar selection practices do not sufficiently prepare for climatic uncertainty and variability. Consequently, the demand for climate resilience of staple food crops such as wheat must be better articulated. Assessments and communication of response diversity enable collective learning across supply chains. Increased awareness could foster governance of resilience through research and breeding programs, incentives, and regulation.}, } @article {pmid30584093, year = {2019}, author = {}, title = {Correction for Girard et al., Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {334-336}, doi = {10.1073/pnas.1820916116}, pmid = {30584093}, issn = {1091-6490}, } @article {pmid30584092, year = {2019}, author = {Lomakin, IB and Dmitriev, SE and Steitz, TA}, title = {Crystal structure of the DENR-MCT-1 complex revealed zinc-binding site essential for heterodimer formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {528-533}, doi = {10.1073/pnas.1809688116}, pmid = {30584092}, issn = {1091-6490}, abstract = {The density-regulated protein (DENR) and the malignant T cell-amplified sequence 1 (MCT-1/MCTS1) oncoprotein support noncanonical translation initiation, promote translation reinitiation on a specific set of mRNAs with short upstream reading frames, and regulate ribosome recycling. DENR and MCT-1 form a heterodimer, which binds to the ribosome. We determined the crystal structure of the heterodimer formed by human MCT-1 and the N-terminal domain of DENR at 2.0-Å resolution. The structure of the heterodimer reveals atomic details of the mechanism of DENR and MCT-1 interaction. Four conserved cysteine residues of DENR (C34, C37, C44, C53) form a classical tetrahedral zinc ion-binding site, which preserves the structure of the DENR's MCT-1-binding interface that is essential for the dimerization. Substitution of all four cysteines by alanine abolished a heterodimer formation. Our findings elucidate further the mechanism of regulation of DENR-MCT-1 activities in unconventional translation initiation, reinitiation, and recycling.}, } @article {pmid30584091, year = {2019}, author = {Xu, HX and Qian, LX and Wang, XW and Shao, RX and Hong, Y and Liu, SS and Wang, XW}, title = {A salivary effector enables whitefly to feed on host plants by eliciting salicylic acid-signaling pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {490-495}, doi = {10.1073/pnas.1714990116}, pmid = {30584091}, issn = {1091-6490}, abstract = {Phloem-feeding insects feed on plant phloem using their stylets. While ingesting phloem sap, these insects secrete saliva to circumvent plant defenses. Previous studies have shown that, to facilitate their feeding, many phloem-feeding insects can elicit the salicylic acid- (SA-) signaling pathway and thus suppress effective jasmonic acid defenses. However, the molecular basis for the regulation of the plant's defense by phloem-feeding insects remains largely unknown. Here, we show that Bt56, a whitefly-secreted low molecular weight salivary protein, is highly expressed in the whitefly primary salivary gland and is delivered into host plants during feeding. Overexpression of the Bt56 gene in planta promotes susceptibility of tobacco to the whitefly and elicits the SA-signaling pathway. In contrast, silencing the whitefly Bt56 gene significantly decreases whitefly performance on host plants and interrupts whitefly phloem feeding with whiteflies losing the ability to activate the SA pathway. Protein-protein interaction assays show that the Bt56 protein directly interacts with a tobacco KNOTTED 1-like homeobox transcription factor that decreases whitefly performance and suppresses whitefly-induced SA accumulation. The Bt56 orthologous genes are highly conserved but differentially expressed in different species of whiteflies. In conclusion, Bt56 is a key salivary effector that promotes whitefly performance by eliciting salicylic acid-signaling pathway.}, } @article {pmid30584090, year = {2019}, author = {Li, C and Bonazzoli, E and Bellone, S and Choi, J and Dong, W and Menderes, G and Altwerger, G and Han, C and Manzano, A and Bianchi, A and Pettinella, F and Manara, P and Lopez, S and Yadav, G and Riccio, F and Zammataro, L and Zeybek, B and Yang-Hartwich, Y and Buza, N and Hui, P and Wong, S and Ravaggi, A and Bignotti, E and Romani, C and Todeschini, P and Zanotti, L and Zizioli, V and Odicino, F and Pecorelli, S and Ardighieri, L and Silasi, DA and Litkouhi, B and Ratner, E and Azodi, M and Huang, GS and Schwartz, PE and Lifton, RP and Schlessinger, J and Santin, AD}, title = {Mutational landscape of primary, metastatic, and recurrent ovarian cancer reveals c-MYC gains as potential target for BET inhibitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {619-624}, doi = {10.1073/pnas.1814027116}, pmid = {30584090}, issn = {1091-6490}, abstract = {Ovarian cancer remains the most lethal gynecologic malignancy. We analyzed the mutational landscape of 64 primary, 41 metastatic, and 17 recurrent fresh-frozen tumors from 77 patients along with matched normal DNA, by whole-exome sequencing (WES). We also sequenced 13 pairs of synchronous bilateral ovarian cancer (SBOC) to evaluate the evolutionary history. Lastly, to search for therapeutic targets, we evaluated the activity of the Bromodomain and Extra-Terminal motif (BET) inhibitor GS-626510 on primary tumors and xenografts harboring c-MYC amplifications. In line with previous studies, the large majority of germline and somatic mutations were found in BRCA1/2 (21%) and TP53 (86%) genes, respectively. Among mutations in known cancer driver genes, 77% were transmitted from primary tumors to metastatic tumors, and 80% from primary to recurrent tumors, indicating that driver mutations are commonly retained during ovarian cancer evolution. Importantly, the number, mutation spectra, and signatures in matched primary-metastatic tumors were extremely similar, suggesting transcoelomic metastases as an early dissemination process using preexisting metastatic ability rather than an evolution model. Similarly, comparison of SBOC showed extensive sharing of somatic mutations, unequivocally indicating a common ancestry in all cases. Among the 17 patients with matched tumors, four patients gained PIK3CA amplifications and two patients gained c-MYC amplifications in the recurrent tumors, with no loss of amplification or gain of deletions. Primary cell lines and xenografts derived from chemotherapy-resistant tumors demonstrated sensitivity to JQ1 and GS-626510 (P = 0.01), suggesting that oral BET inhibitors represent a class of personalized therapeutics in patients harboring recurrent/chemotherapy-resistant disease.}, } @article {pmid30584089, year = {2019}, author = {Leung, KK and Nguyen, A and Shi, T and Tang, L and Ni, X and Escoubet, L and MacBeth, KJ and DiMartino, J and Wells, JA}, title = {Multiomics of azacitidine-treated AML cells reveals variable and convergent targets that remodel the cell-surface proteome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {695-700}, doi = {10.1073/pnas.1813666116}, pmid = {30584089}, issn = {1091-6490}, abstract = {Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are diseases of abnormal hematopoietic differentiation with aberrant epigenetic alterations. Azacitidine (AZA) is a DNA methyltransferase inhibitor widely used to treat MDS and AML, yet the impact of AZA on the cell-surface proteome has not been defined. To identify potential therapeutic targets for use in combination with AZA in AML patients, we investigated the effects of AZA treatment on four AML cell lines representing different stages of differentiation. The effect of AZA treatment on these cell lines was characterized at three levels: the DNA methylome, the transcriptome, and the cell-surface proteome. Untreated AML cell lines showed substantial overlap at all three omics levels; however, while AZA treatment globally reduced DNA methylation in all cell lines, changes in the transcriptome and surface proteome were subtle and differed among the cell lines. Transcriptome analysis identified five commonly up-regulated coding genes upon AZA treatment in all four cell lines, TRPM4 being the only gene encoding a surface protein, and surface proteome analysis found no commonly regulated proteins. Gene set enrichment analysis of differentially regulated RNA and surface proteins showed a decrease in metabolic pathways and an increase in immune defense response pathways. As such, AZA treatment led to diverse effects at the individual gene and protein levels but converged to common responses at the pathway level. Given the heterogeneous responses in the four cell lines, we discuss potential therapeutic strategies for AML in combination with AZA.}, } @article {pmid30584088, year = {2019}, author = {Chi, C and Leonard, A and Knight, WE and Beussman, KM and Zhao, Y and Cao, Y and Londono, P and Aune, E and Trembley, MA and Small, EM and Jeong, MY and Walker, LA and Xu, H and Sniadecki, NJ and Taylor, MR and Buttrick, PM and Song, K}, title = {LAMP-2B regulates human cardiomyocyte function by mediating autophagosome-lysosome fusion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {556-565}, doi = {10.1073/pnas.1808618116}, pmid = {30584088}, issn = {1091-6490}, abstract = {Mutations in lysosomal-associated membrane protein 2 (LAMP-2) gene are associated with Danon disease, which often leads to cardiomyopathy/heart failure through poorly defined mechanisms. Here, we identify the LAMP-2 isoform B (LAMP-2B) as required for autophagosome-lysosome fusion in human cardiomyocytes (CMs). Remarkably, LAMP-2B functions independently of syntaxin 17 (STX17), a protein that is essential for autophagosome-lysosome fusion in non-CMs. Instead, LAMP-2B interacts with autophagy related 14 (ATG14) and vesicle-associated membrane protein 8 (VAMP8) through its C-terminal coiled coil domain (CCD) to promote autophagic fusion. CMs derived from induced pluripotent stem cells (hiPSC-CMs) from Danon patients exhibit decreased colocalization between ATG14 and VAMP8, profound defects in autophagic fusion, as well as mitochondrial and contractile abnormalities. This phenotype was recapitulated by LAMP-2B knockout in non-Danon hiPSC-CMs. Finally, gene correction of LAMP-2 mutation rescues the Danon phenotype. These findings reveal a STX17-independent autophagic fusion mechanism in human CMs, providing an explanation for cardiomyopathy in Danon patients and a foundation for targeting defective LAMP-2B-mediated autophagy to treat this patient population.}, } @article {pmid30584087, year = {2019}, author = {Wieczynski, DJ and Boyle, B and Buzzard, V and Duran, SM and Henderson, AN and Hulshof, CM and Kerkhoff, AJ and McCarthy, MC and Michaletz, ST and Swenson, NG and Asner, GP and Bentley, LP and Enquist, BJ and Savage, VM}, title = {Climate shapes and shifts functional biodiversity in forests worldwide.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {587-592}, doi = {10.1073/pnas.1813723116}, pmid = {30584087}, issn = {1091-6490}, abstract = {Much ecological research aims to explain how climate impacts biodiversity and ecosystem-level processes through functional traits that link environment with individual performance. However, the specific climatic drivers of functional diversity across space and time remain unclear due largely to limitations in the availability of paired trait and climate data. We compile and analyze a global forest dataset using a method based on abundance-weighted trait moments to assess how climate influences the shapes of whole-community trait distributions. Our approach combines abundance-weighted metrics with diverse climate factors to produce a comprehensive catalog of trait-climate relationships that differ dramatically-27% of significant results change in sign and 71% disagree on sign, significance, or both-from traditional species-weighted methods. We find that (i) functional diversity generally declines with increasing latitude and elevation, (ii) temperature variability and vapor pressure are the strongest drivers of geographic shifts in functional composition and ecological strategies, and (iii) functional composition may currently be shifting over time due to rapid climate warming. Our analysis demonstrates that climate strongly governs functional diversity and provides essential information needed to predict how biodiversity and ecosystem function will respond to climate change.}, } @article {pmid30583849, year = {2018}, author = {Dundas, K and Shears, MJ and Sinnis, P and Wright, GJ}, title = {Important Extracellular Interactions between Plasmodium Sporozoites and Host Cells Required for Infection.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.008}, pmid = {30583849}, issn = {1471-5007}, support = {R01 AI056840/AI/NIAID NIH HHS/United States ; R01 AI132359/AI/NIAID NIH HHS/United States ; }, abstract = {Malaria is an infectious disease, caused by Plasmodium parasites, that remains a major global health problem. Infection begins when salivary gland sporozoites are transmitted through the bite of an infected mosquito. Once within the host, sporozoites navigate through the dermis, into the bloodstream, and eventually invade hepatocytes. While we have an increasingly sophisticated cellular description of this journey, our molecular understanding of the extracellular interactions between the sporozoite and mammalian host that regulate migration and invasion remain comparatively poor. Here, we review the current state of our understanding, highlight the technical limitations that have frustrated progress, and outline how new approaches will help to address this knowledge gap with the ultimate aim of improving malaria treatments.}, } @article {pmid30583846, year = {2019}, author = {Bobe, R and Carvalho, S}, title = {Hominin diversity and high environmental variability in the Okote Member, Koobi Fora Formation, Kenya.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {91-105}, doi = {10.1016/j.jhevol.2018.10.012}, pmid = {30583846}, issn = {1095-8606}, abstract = {The newly described partial skeleton of Paranthropus boisei KNM-ER 47000 as well as the FwJj14E Ileret footprints provide new evidence on the paleobiology and diversity of hominins from the Okote Member of the Koobi Fora Formation at East Turkana about 1.5 Ma. To better understand the ecological context of the Okote hominins, it is necessary to broaden the geographical focus of the analysis to include the entire Omo-Turkana ecosystem, and the temporal focus to encompass the early Pleistocene. Previous work has shown that important changes in the regional vegetation occurred after 2 Ma, and that there was a peak in mammalian turnover and diversity close to 1.8 Ma. This peak in diversity included the Hominini, with the species P. boisei, Homo habilis, Homo rudolfensis, and Homo erectus co-occurring at around 1.8 Ma. There is considerable debate about whether H. habilis and H. rudolfensis indeed constitute separate species, but even if we consider them both as H. habilis sensu lato, the co-occurrence of three hominin species at any one time and place is rather unusually high diversity for hominin standards (even if not so for other mammalian groups such as suids, bovids, or cercopithecids). Here we use mammalian faunal abundance data to place confidence intervals on first and last appearances of hominin species in the early Pleistocene of the Omo-Turkana Basin, and use these estimates to discuss hominin diversity in the Okote Member. We suggest that in the early Pleistocene a wide range of depositional environments and vegetation types, along with a high frequency of volcanism, likely maintained high levels of environmental variability both in time and space across the Omo-Turkana region, and provided ecological opportunities for the coexistence of at least three hominin species alongside a diverse mammalian fauna.}, } @article {pmid30583845, year = {2019}, author = {Marigó, J and Verrière, N and Godinot, M}, title = {Systematic and locomotor diversification of the Adapis group (Primates, Adapiformes) in the late Eocene of the Quercy (Southwest France), revealed by humeral remains.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {71-90}, doi = {10.1016/j.jhevol.2018.10.009}, pmid = {30583845}, issn = {1095-8606}, abstract = {Twenty humeral specimens from the old and new Quercy collections attributed to the fossil primates Adapis and Palaeolemur are described and analysed together. We provide a qualitative and quantitative analysis of the different humeri, revealing that high variability is present within the "Adapis group" sample. Six different morphotypes are identified, confirming that what has often been called "Adapis parisiensis" is a mix of different species that present different locomotor adaptations. Such a relatively high level of locomotor diversity is unique in the Paleogene primate fossil record. The humeral proportions of Adapis overlap with different groups of extant strepsirrhines and platyrrhines depending on the specimen, so the popular view of Adapis as a loris-like slow climbing primate does not apply to the whole sample presented here. Moreover, different humeral features traditionally associated with "Adapis parisiensis", such as the absence of a zona conoidea and a reduced brachioradialis flange, are variable depending on the sample studied. In addition, results of our analyses show that adapine and omomyid humeral morphology overlap extensively, leading us to question the accuracy of taxonomic attributions based on morphology of isolated humeri at localities where omomyids and adapines of similar size coexist. Finally, assuming our different morphotypes represent different species within two genera, we propose a phylogenetic hypothesis relating these morphotypes, which inhabited a small geographic area.}, } @article {pmid30583844, year = {2019}, author = {Lague, MR and Chirchir, H and Green, DJ and Mbua, E and Harris, JWK and Braun, DR and Griffin, NL and Richmond, BG}, title = {Cross-sectional properties of the humeral diaphysis of Paranthropus boisei: Implications for upper limb function.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {51-70}, doi = {10.1016/j.jhevol.2018.05.002}, pmid = {30583844}, issn = {1095-8606}, abstract = {A ∼1.52 Ma adult upper limb skeleton of Paranthropus boisei (KNM-ER 47000) recovered from the Koobi Fora Formation, Kenya (FwJj14E, Area 1A) includes most of the distal half of a right humerus (designated KNM-ER 47000B). Natural transverse fractures through the diaphysis of KNM-ER 470000B provide unobstructed views of cortical bone at two sections typically used for analyzing cross-sectional properties of hominids (i.e., 35% and 50% of humerus length from the distal end). Here we assess cross-sectional properties of KNM-ER 47000B and two other P. boisei humeri (OH 80-10, KNM-ER 739). Cross-sectional properties for P. boisei associated with bending/torsional strength (section moduli) and relative cortical thickness (%CA; percent cortical area) are compared to those reported for nonhuman hominids, AL 288-1 (Australopithecus afarensis), and multiple species of fossil and modern Homo. Polar section moduli (Zp) are assessed relative to a mechanically relevant measure of body size (i.e., the product of mass [M] and humerus length [HL]). At both diaphyseal sections, P. boisei exhibits %CA that is high among extant hominids (both human and nonhuman) and similar to that observed among specimens of Pleistocene Homo. High values for Zp relative to size (M × HL) indicate that P. boisei had humeral bending strength greater than that of modern humans and Neanderthals and similar to that of great apes, A. afarensis, and Homo habilis. Such high humeral strength is consistent with other skeletal features of P. boisei (reviewed here) that suggest routine use of powerful upper limbs for arboreal climbing.}, } @article {pmid30583843, year = {2019}, author = {Fagot, J and Boë, LJ and Berthomier, F and Claidière, N and Malassis, R and Meguerditchian, A and Rey, A and Montant, M}, title = {The baboon: A model for the study of language evolution.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {39-50}, doi = {10.1016/j.jhevol.2018.10.006}, pmid = {30583843}, issn = {1095-8606}, abstract = {Comparative research on the origins of human language often focuses on a limited number of language-related cognitive functions or anatomical structures that are compared across species. The underlying assumption of this approach is that a single or a limited number of factors may crucially explain how language appeared in the human lineage. Another potentially fruitful approach is to consider human language as the result of a (unique) assemblage of multiple cognitive and anatomical components, some of which are present in other species. This paper is a first step in that direction. It focuses on the baboon, a non-human primate that has been studied extensively for years, including several brain, anatomical, cognitive and cultural dimensions that are involved in human language. This paper presents recent data collected on baboons regarding (1) a selection of domain-general cognitive functions that are core functions for language, (2) vocal production, (3) gestural production and cerebral lateralization, and (4) cumulative culture. In all these domains, it shows that the baboons share with humans many cognitive or brain mechanisms which are central for language. Because of the multidimensionality of the knowledge accumulated on the baboon, that species is an excellent nonhuman primate model for the study of the evolutionary origins of language.}, } @article {pmid30583842, year = {2019}, author = {Lague, MR and Chirchir, H and Green, DJ and Mbua, E and Harris, JWK and Braun, DR and Griffin, NL and Richmond, BG}, title = {Humeral anatomy of the KNM-ER 47000 upper limb skeleton from Ileret, Kenya: Implications for taxonomic identification.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {24-38}, doi = {10.1016/j.jhevol.2018.06.011}, pmid = {30583842}, issn = {1095-8606}, abstract = {KNM-ER 47000 is a fossil hominin upper limb skeleton from the Koobi Fora Formation, Kenya (FwJj14E, Area 1A) that includes portions of the scapula, humerus, ulna, and hand. Dated to ∼1.52 Ma, the skeleton could potentially belong to one of multiple hominin species that have been documented in the Turkana Basin during this time, including Homo habilis, Homo erectus, and Paranthropus boisei. Although the skeleton lacks associated craniodental material, the partial humerus (described here) preserves anatomical regions (i.e., distal diaphysis, elbow joint) that are informative for taxonomic identification among early Pleistocene hominins. In this study, we analyze distal diaphyseal morphology and the shape of the elbow region to determine whether KNM-ER 47000 can be confidently attributed to a particular species. The morphology of the KNM-ER 47000 humerus (designated KNM-ER 47000B) is compared to that of other early Pleistocene hominin fossil humeri via the application of multivariate ordination techniques to both two-dimensional landmark data (diaphysis) and scale-free linear shape data (elbow). Distance metrics reflecting shape dissimilarity between KNM-ER 47000B and other fossils (and species average shapes) are assessed in the context of intraspecific variation within modern hominid species (Homo sapiens, Pan troglodytes, Gorilla gorilla, Pongo pygmaeus). Our comparative analyses strongly support attribution of KNM-ER 47000 to P. boisei. Compared to four other partial skeletons that have (justifiably or not) been attributed to P. boisei, KNM-ER 47000 provides the most complete picture of upper limb anatomy in a single individual. The taxonomic identification of KNM-ER 47000 makes the skeleton an important resource for testing future hypotheses related to P. boisei upper limb function and the taxonomy of isolated early Pleistocene hominin remains.}, } @article {pmid30583841, year = {2019}, author = {Bonnell, TR and Henzi, SP and Barrett, L}, title = {Functional social structure in baboons: Modeling interactions between social and environmental structure in group-level foraging.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {14-23}, doi = {10.1016/j.jhevol.2018.10.011}, pmid = {30583841}, issn = {1095-8606}, abstract = {In mobile social groups, cohesion is thought to be driven by patterns of attraction at both the individual and group level. In long-lived species with high group stability and repeated interactions, such as baboons, individual-to-individual attractions have the potential to play a large role in group cohesion and overall movement patterns. In previous work, we found that the patterning of inter-individual attraction gave rise to an emergent group-level structure, whereby a core of more influential, inter-dependent individuals exerted a unidirectional influence on the movements of peripheral animals. Here, we use agent-based modeling of baboon groups to investigate whether this core-periphery structure has any functional consequences for foraging behavior. By varying individual level attractions, we produced baboon groups that contained influence structures that varied from more to less centralized. Our results suggest that varying centrality affects both the ability of the group to detect resource structure in the environment, as well as the ability of the group to exploit these resources. Our models predict that foraging groups with more centralized social structures will show a reduction in detection and an increase in exploitation of resources in their environment, and will produce more extreme foraging outcomes. More generally, our results highlight how a group's internal social structure can result in mobile social animals being able to more (or less) effectively exploit environmental structure, and capitalize on the distribution of resources. In addition, our agent-based model can be used to generate testable predictions that can be tested among the extant baboon allotaxa. This will add value to the existing body of work on responses to local ecology, as well as providing a means to test hypotheses relating to the phylogeography of the baboons and, by analogy, shed light on patterns of hominin evolution in time and space.}, } @article {pmid30583840, year = {2019}, author = {Beaudet, A and Clarke, RJ and de Jager, EJ and Bruxelles, L and Carlson, KJ and Crompton, R and de Beer, F and Dhaene, J and Heaton, JL and Jakata, K and Jashashvili, T and Kuman, K and McClymont, J and Pickering, TR and Stratford, D}, title = {The endocast of StW 573 ("Little Foot") and hominin brain evolution.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {112-123}, doi = {10.1016/j.jhevol.2018.11.009}, pmid = {30583840}, issn = {1095-8606}, abstract = {One of the most crucial debates in human paleoneurology concerns the timing and mode of the emergence of the derived cerebral features in the hominin fossil record. Given its exceptional degree of preservation and geological age (i.e., 3.67 Ma), StW 573 ('Little Foot') has the potential to shed new light on hominin brain evolution. Here we present the first detailed comparative description of the external neuroanatomy of StW 573. The endocast was virtually reconstructed and compared to ten southern African hominin specimens from Makapansgat, Malapa, Sterkfontein and Swartkrans attributed to Australopithecus and Paranthropus. We apply an automatic method for the detection of sulcal and vascular imprints. The endocranial surface of StW 573 is crushed and plastically deformed in a number of locations. The uncorrected and therefore minimum cranial capacity estimate is 408 cm3 and plots at the lower end of Australopithecus variation. The endocast of StW 573 approximates the rostrocaudally elongated and dorsoventrally flattened endocranial shape seen in Australopithecus and displays a distinct left occipital petalia. StW 573 and the comparative early hominin specimens share a similar sulcal pattern in the inferior region of the frontal lobes that also resembles the pattern observed in extant chimpanzees. The presumed lunate sulcus in StW 573 is located above the sigmoid sinus, as in extant chimpanzees, while it is more caudally positioned in SK 1585 and StW 505. The middle branch of the middle meningeal vessels derives from the anterior branch, as in MH 1, MLD 37/38, StW 578. Overall, the cortical anatomy of StW 573 displays a less derived condition compared to the late Pliocene/early Pleistocene southern African hominins (e.g., StW 505, SK 1585).}, } @article {pmid30583839, year = {2019}, author = {Ackermann, RR}, title = {Reflections on the history and legacy of scientific racism in South African paleoanthropology and beyond.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {106-111}, doi = {10.1016/j.jhevol.2018.11.007}, pmid = {30583839}, issn = {1095-8606}, } @article {pmid30583838, year = {2019}, author = {Hammerschmidt, K and Fischer, J}, title = {Baboon vocal repertoires and the evolution of primate vocal diversity.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {1-13}, doi = {10.1016/j.jhevol.2018.10.010}, pmid = {30583838}, issn = {1095-8606}, abstract = {A remarkable and derived trait of humans is the faculty for language, and considerable research effort has been devoted to understanding the evolution of speech. In contrast to spoken language, which constitutes a (learned) symbolic communication system, the acoustic structure of nonhuman primate vocalizations is largely genetically fixed. Yet, appreciable differences between different genera and species may exist. Environmental conditions, sexual selection, and characteristics of the social system have been invoked to explain these differences. Here, we studied the acoustic variation of call types and vocal repertoires in the genus Papio. Because the genus comprises both stable groups as well as multi-level societies, and reveals striking variation in the degree of aggressiveness from south to north, it constitutes a promising model to assess the link between social system characteristics and vocal communication. We found that, the vocal repertoires of the different species were composed of the same general call types. A quantitative analysis of the acoustic features of the grunts and loud calls of chacma (Papio ursinus), olive (P. anubis), and Guinea (P. papio) baboons showed subtle acoustic differences within call types, however. Social system characteristics did not map onto acoustic variation. We found no correlation between the structure of grunts and geographic distance; the same was true for female loud calls. Only for male loud calls from three populations, call structure varied with geographic distance. Our findings corroborate the view that the structure of nonhuman primate vocalizations is highly conserved, despite the differences in social systems. Apparently, variation in rate and intensity of occurrence of signals, probably due to different behavioral dispositions in species, are sufficient to allow for plasticity at the level of the social relationships, mating patterns, and social organization.}, } @article {pmid30583805, year = {2019}, author = {Fragata, I and Blanckaert, A and Dias Louro, MA and Liberles, DA and Bank, C}, title = {Evolution in the light of fitness landscape theory.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {69-82}, doi = {10.1016/j.tree.2018.10.009}, pmid = {30583805}, issn = {1872-8383}, abstract = {By formalizing the relationship between genotype or phenotype and fitness, fitness landscapes harbor information on molecular and evolutionary constraints. The shape of the fitness landscape determines the potential for adaptation and speciation, as well as our ability to predict evolution. Consequently, fitness landscape theory has been invoked across the natural sciences and across multiple levels of biological organization. We review here the existing literature on fitness landscape theory by describing the main types of fitness landscape models, and highlight how these are increasingly integrated into an applicable statistical framework for the study of evolution. Specifically, we demonstrate how the interpretation of experimental studies with respect to fitness landscape models enables a direct link between evolution, molecular biology, and systems biology.}, } @article {pmid30583796, year = {2018}, author = {Hudson, C and Esposito, R and Palladino, A and Staiano, L and Ferrier, D and Faure, E and Lemaire, P and Yasuo, H and Spagnuolo, A}, title = {Transcriptional regulation of the Ciona Gsx gene in the neural plate.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.013}, pmid = {30583796}, issn = {1095-564X}, abstract = {The ascidian neural plate consists of a defined number of identifiable cells organized in a grid of rows and columns, representing a useful model to investigate the molecular mechanisms controlling neural patterning in chordates. Distinct anterior brain lineages are specified via unique combinatorial inputs of signalling pathways with Nodal and Delta-Notch signals patterning along the medial-lateral axis and FGF/MEK/ERK signals patterning along the anterior-posterior axis of the neural plate. The Ciona Gsx gene is specifically expressed in the a9.33 cells in the row III/column 2 position of anterior brain lineages, characterised by a combinatorial input of Nodal-OFF, Notch-ON and FGF-ON. Here, we identify the minimal cis-regulatory element (CRE) of 376 bp, which can recapitulate the early activation of Gsx. We show that this minimal CRE responds in the same way as the endogenous Gsx gene to manipulation of FGF- and Notch-signalling pathways and to overexpression of Snail, a mediator of Nodal signals, and Six3/6, which is required to demarcate the anterior boundary of Gsx expression at the late neurula stage. We reveal that sequences proximal to the transcription start site include a temporal regulatory element required for the precise transcriptional onset of gene expression. We conclude that sufficient spatial and temporal information for Gsx expression is integrated in 376 bp of non-coding cis-regulatory sequences.}, } @article {pmid30583727, year = {2018}, author = {O'Carroll, A and Chauvin, B and Brown, JWP and Meagher, A and Coyle, J and Schill, J and Bhumkhar, A and Hunter, DJB and Ve, T and Kobe, B and Sierecki, E and Gambin, Y}, title = {Pathological mutations differentially affect the self-assembly and polymerisation of the innate immune system signalling adaptor molecule MyD88.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {149}, doi = {10.1186/s12915-018-0611-7}, pmid = {30583727}, issn = {1741-7007}, abstract = {BACKGROUND: Higher-order self-assembly of proteins, or "prion-like" polymerisation, is now emerging as a simple and robust mechanism for signal amplification, in particular within the innate immune system, where the recognition of pathogens or danger-associated molecular patterns needs to trigger a strong, binary response within cells. MyD88, an important adaptor protein downstream of TLRs, is one of the most recent candidates for involvement in signalling by higher order self-assembly. In this new light, we set out to re-interpret the role of polymerisation in MyD88-related diseases and study the impact of disease-associated point mutations L93P, R196C, and L252P/L265P at the molecular level.

RESULTS: We first developed new in vitro strategies to characterise the behaviour of polymerising, full-length MyD88 at physiological levels. To this end, we used single-molecule fluorescence fluctuation spectroscopy coupled to a eukaryotic cell-free protein expression system. We were then able to explore the polymerisation propensity of full-length MyD88, at low protein concentration and without purification, and compare it to the behaviours of the isolated TIR domain and death domain that have been shown to have self-assembly properties on their own. These experiments demonstrate that the presence of both domains is required to cooperatively lead to efficient polymerisation of the protein. We then characterised three pathological mutants of MyD88.

CONCLUSION: We discovered that all mutations block the ability of MyD88 to polymerise fully. Interestingly, we show that, in contrast to L93P and R196C, L252P is a gain-of-function mutation, which allows the MyD88 mutant to form extremely stable oligomers, even at low nanomolar concentrations. Thus, our results shed new light on the digital "all-or-none" responses by the myddosomes and the behaviour of the oncogenic mutations of MyD88.}, } @article {pmid30583719, year = {2018}, author = {Romagnoli, D and Boccalini, G and Bonechi, M and Biagioni, C and Fassan, P and Bertorelli, R and De Sanctis, V and Di Leo, A and Migliaccio, I and Malorni, L and Benelli, M}, title = {ddSeeker: a tool for processing Bio-Rad ddSEQ single cell RNA-seq data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {960}, doi = {10.1186/s12864-018-5249-x}, pmid = {30583719}, issn = {1471-2164}, support = {NA//Fondazione Cassa di Risparmio di Firenze (IT)/ ; 14371//Associazione Italiana per la Ricerca sul Cancro/ ; 18880//Associazione Italiana per la Ricerca sul Cancro/ ; }, abstract = {BACKGROUND: New single-cell isolation technologies are facilitating studies on the transcriptomics of individual cells. Bio-Rad ddSEQ is a droplet-based microfluidic system that, when coupled with downstream Illumina library preparation and sequencing, enables the monitoring of thousands of genes per cell. Sequenced reads show unique features that do not permit the use of freely available tools to perform single cell demultiplexing.

RESULTS: We present ddSeeker, a tool to perform initial processing and quality metrics of reads generated through Bio-Rad ddSEQ/Illumina experiments. Its application to the Illumina test dataset demonstrates that ddSeeker performs better than Illumina BaseSpace software, enabling a higher recovery of valid reads. We also show its utility in the analysis of an in-house dataset including two read sets characterized by low and high sequencing quality. ddSeeker and its source code are available at https://github.com/cgplab/ddSeeker .

CONCLUSIONS: ddSeeker is a freely available tool to perform initial processing and quality metrics of reads generated through Bio-Rad ddSEQ/Illumina single cell transcriptomic experiments.}, } @article {pmid30583043, year = {2018}, author = {Sousa-Santos, C and Jesus, TF and Fernandes, C and Robalo, JI and Coelho, MM}, title = {Fish diversification at the pace of geomorphological changes: evolutionary history of western Iberian Leuciscinae (Teleostei: Leuciscidae) inferred from multilocus sequence data.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {263-285}, doi = {10.1016/j.ympev.2018.12.020}, pmid = {30583043}, issn = {1095-9513}, abstract = {The evolutionary history of western Iberian Leuciscinae, obligatory freshwater fish, is directly linked to the evolution of the hydrographic network of the Iberian Peninsula after its isolation from the rest of Europe, which involved dramatic rearrangements such as the transition from endorheic lakes to open basins draining to the Atlantic. Previous phylogenetic research on western Iberian leuciscines, using mainly mitochondrial DNA and more recently one or two nuclear genes, has found contradictory results and there remain many unresolved issues regarding species relationships, taxonomy, and evolutionary history. Moreover, there is a lack of integration between phylogenetic and divergence time estimates and information on the timing of geomorphological changes and paleobasin rearrangements in the Iberian Peninsula. This study presents the first comprehensive fossil-calibrated multilocus coalescent species tree of western Iberian Leuciscinae (including 14 species of Achondrostoma, Iberochondrostoma, Pseudochondrostoma and Squalius endemic to the Iberian Peninsula, seven of which endemic to Portugal) based on seven nuclear genes, and from which we infer their biogeographic history by comparing divergence time estimates to known dated geological events. The phylogenetic pattern suggests slow-paced evolution of leuciscines during the Early-Middle Miocene endorheic phase of the main Iberian river basins, with the shift to exorheism in the late Neogene-Quaternary allowing westward dispersals that resulted in many cladogenetic events and a high rate of endemism in western Iberia. The results of this study also: (i) confirm the paraphyly of S. pyrenaicus with respect to S. carolitertii, and thus the possible presence of a new taxon in the Portuguese Tagus currently assigned to S. pyrenaicus; (ii) support the taxonomic separation of the Guadiana and Sado populations of S. pyrenaicus; (iii) show the need for further population sampling and taxonomic research to clarify the phylogenetic status of A. arcasii from the Minho basin and of the I. lusitanicum populations in the Sado and Tagus basins; and (iv) indicate that A. occidentale, I. olisiponensis and P. duriensis are the most ancient lineages within their respective genera.}, } @article {pmid30583042, year = {2018}, author = {Elias-Costa, AJ and Confalonieri, VA and Lanteri, AA and Rodriguero, MS}, title = {Game of clones: Is Wolbachia inducing speciation in a weevil with a mixed reproductive mode?.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {42-53}, doi = {10.1016/j.ympev.2018.12.027}, pmid = {30583042}, issn = {1095-9513}, abstract = {Parthenogenesis is widely distributed in Metazoa but it is especially frequent in weevils (Coleoptera, Curculionidae) with one fifth of all known cases. Previous studies have shown that in the tribe Naupactini parthenogenetic reproduction most likely originated with an infection of the endoparasitic bacterium Wolbachia pipientis. In particular, Pantomorus postfasciatus possess a mixed reproductive mode: some populations have males while in others they are absent, and females produce clones by thelytoky. To better understand this scenario, we studied the population structure and infection status in 64 individuals of P. postfasciatus from Argentina and Brazil. We sequenced two mitochondrial (COI and COII) and one nuclear (ITS-1) fragments and obtained two very divergent haplogroups, one corresponding to the sexual populations uninfected with Wolbachia, and another conforming a monophyletic parthenogenetic (or presumptively parthenogenetic) and infected clade. Each of these haplogroups was identified as an independently evolutionary unit by all species delimitation analyses accomplished: multilocus *BEAST and BP&P, and single locus GMYC and K/θ rule. Additionally, present evidence suggests that Wolbachia infection occurred at least twice in all-female populations of P. postfasciatus with two different bacterial strains. Speciation mediated by Wolbachia is a recently described phenomenon and the case of P. postfasciatus is the first known case in a diplo-diploid insect. A model that describes how thelytoky-inducing phenotypes of Wolbachia could generate new lineages is discussed.}, } @article {pmid30581192, year = {2018}, author = {Khramtsova, EA and Davis, LK and Stranger, BE}, title = {The role of sex in the genomics of human complex traits.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41576-018-0083-1}, pmid = {30581192}, issn = {1471-0064}, abstract = {Nearly all human complex traits and disease phenotypes exhibit some degree of sex differences, including differences in prevalence, age of onset, severity or disease progression. Until recently, the underlying genetic mechanisms of such sex differences have been largely unexplored. Advances in genomic technologies and analytical approaches are now enabling a deeper investigation into the effect of sex on human health traits. In this Review, we discuss recent insights into the genetic models and mechanisms that lead to sex differences in complex traits. This knowledge is critical for developing deeper insight into the fundamental biology of sex differences and disease processes, thus facilitating precision medicine.}, } @article {pmid30580972, year = {2018}, author = {Nakagawa, S and Samarasinghe, G and Haddaway, NR and Westgate, MJ and O'Dea, RE and Noble, DWA and Lagisz, M}, title = {Research Weaving: Visualizing the Future of Research Synthesis.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2018.11.007}, pmid = {30580972}, issn = {1872-8383}, abstract = {We propose a new framework for research synthesis of both evidence and influence, named research weaving. It summarizes and visualizes information content, history, and networks among a collection of documents on any given topic. Research weaving achieves this feat by combining the power of two methods: systematic mapping and bibliometrics. Systematic mapping provides a snapshot of the current state of knowledge, identifying areas needing more research attention and those ready for full synthesis. Bibliometrics enables researchers to see how pieces of evidence are connected, revealing the structure and development of a field. We explain how researchers can use some or all of these tools to gain a deeper, more nuanced understanding of the scientific literature.}, } @article {pmid30580331, year = {2018}, author = {Díaz Casana, CF and Vivas Ruíz, DE and Sandoval Peña, GA and Chimoy Effio, PJ}, title = {Molecular Sexing of the White-Winged Guan (Penelope albipennis) and Other Wild Birds of the North of Peru.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000495383}, pmid = {30580331}, issn = {1661-5433}, abstract = {The use of accurate and reliable techniques for sex determination of wild birds is of special importance in captive breeding programs, especially in birds with monogamous, aggressive behavior, with absence of copulation, and with a low hatching rate. Using PCR, we evaluated the relative efficacy of primers HPF/HPR and CHD1Wr/NP/CHD1Zr in the amplification of the chromo-helicase-DNA binding 1 (CHD1) gene for sex determination in Penelope albipennis and 8 other species of cracids, 4 species of falconids, 4 species of accipitrids, and 3 species of psittacines. Primer effectiveness was compared using previously sexed bird samples. The HPF/HPR primer set was found to demonstrate a better performance and reliability. Therefore, these primers should be used to determine the sex of juvenile birds to avoid or minimize incompatibilities during the selection of potential breeding pairs.}, } @article {pmid30580043, year = {2018}, author = {Bell, NE and Ignatov, MS}, title = {Placing the regionally threatened moss Orthodontium gracile in the big picture - Phylogeny, genome incongruence and anthropogenic dispersal in the order Orthodontiales.}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ympev.2018.12.024}, pmid = {30580043}, issn = {1095-9513}, abstract = {The Orthodontiaceae is a small family of predominantly Southern Hemisphere temperate and South East Asian mosses that has a key phylogenetic position for research into the evolution of pleurocarpy. In the United Kingdom it is represented by the rare conservation priority species Orthodontium gracile and the abundant exotic O. lineare, introduced from the Southern Hemisphere around a century ago. Although the two species are superficially very similar and difficult to tell apart in the field, very little is known about how closely they are related or about the phylogeny, biogeography and evolutionary history of the genus Orthodontium as a whole. Phylogenetic inference and divergence time estimation were used to explore relationships within the genus globally, date major lineage splits, detect reticulate evolutionary processes and test monophyly of taxa. It was shown that Orthodontium gracile belongs to a Holarctic and Asian clade that diverged from the exclusively southern temperate lineage of O. lineare approximately 53 Ma and that it is sister to the Himalayan and South Siberian bispecific genus Orthodontopsis, which we now recognise as a single species within Orthodontium, O. lignicola. Orthodontium lignicola is quite distinct from O. gracile morphologically but may have a closely overlapping centre of extant diversity in the Himalaya, in contrast to O. lineare which is morphologically similar but biogeographically dissimilar. The introduced European populations of Orthodontium lineare were shown to share plastid and nuclear haplotypes with four collections from Tasmania and Southern Chile, but to be distinct from other Chilean and South African haplotypes. Finally, well-supported incongruence between nuclear and plastid sequences in some Western North American populations of Orthodontium gracile strongly implies one or more chloroplast capture or horizontal genome transfer events involving this species and the regionally sympatric O. pellucens. An appeal is made for targeting phylogenetic research at the intersection points of practical conservation, taxonomic uncertainty and wider biological questions and for the factoring of historical evolutionary and phylogenetic diversity into conservation assessments.}, } @article {pmid30579765, year = {2018}, author = {Hutchins, EJ and Bronner, ME}, title = {Draxin alters laminin organization during basement membrane remodeling to control cranial neural crest EMT.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.021}, pmid = {30579765}, issn = {1095-564X}, support = {F32 DE026355/DE/NIDCR NIH HHS/United States ; L40 DE028128/DE/NIDCR NIH HHS/United States ; P01 HD037105/HD/NICHD NIH HHS/United States ; R01 DE024157/DE/NIDCR NIH HHS/United States ; }, abstract = {Premigratory neural crest cells arise within the dorsal neural tube and subsequently undergo an epithelial-to-mesenchymal transition (EMT) to leave the neuroepithelium and initiate migration. Draxin is a Wnt modulator that has been shown to control the timing of cranial neural crest EMT. Here we show that this process is accompanied by three stages of remodeling of the basement membrane protein laminin, from regression to expansion and channel formation. Loss of Draxin results in blocking laminin remodeling at the regression stage, whereas ectopic maintenance of Draxin blocks remodeling at the expansion stage. The latter effect is rescued by addition of Snail2, previously shown to be downstream of Draxin. Our results demonstrate an essential function for the Wnt modulator Draxin in regulating basement membrane remodeling during cranial neural crest EMT.}, } @article {pmid30579764, year = {2018}, author = {Shindo, A and Inoue, Y and Kinoshita, M and Wallingford, JB}, title = {PCP-dependent transcellular regulation of actomyosin oscillation facilitates convergent extension of vertebrate tissue.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.017}, pmid = {30579764}, issn = {1095-564X}, abstract = {Oscillatory flows of actomyosin play a key role in the migration of single cells in culture and in collective cell movements in Drosophila embryos. In vertebrate embryos undergoing convergent extension (CE), the Planar Cell Polarity (PCP) pathway drives the elongation of the body axis and shapes the central nervous system, and mutations of the PCP genes predispose humans to various malformations including neural tube defects. However, the spatiotemporal patterns of oscillatory actomyosin contractions during vertebrate CE and how they are controlled by the PCP signaling remain unknown. Here, we address these outstanding issues using a combination of in vivo imaging and mathematical modeling. We find that effective execution of CE requires alternative oscillations of cortical actomyosin across cell membranes of neighboring cells within an optimal frequency range. Intriguingly, temporal and spatial clustering of the core PCP protein Prickle 2 (Pk2) is correlated to submembranous accumulations of F-actin, and depletion of Pk2 perturbs the oscillation of actomyosin contractions. These findings shed light on the significance of temporal regulation of actomyosin contraction by the PCP pathway during CE, in addition to its well-studied spatial aspects.}, } @article {pmid30579700, year = {2018}, author = {Ng, SS and Engwerda, CR}, title = {Innate Lymphocytes and Malaria - Players or Spectators?.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.012}, pmid = {30579700}, issn = {1471-5007}, abstract = {Malaria remains an important global disease. Despite significant advances over the past decade in reducing disease morbidity and mortality, new measures are needed if malaria is to be eliminated. Significant advances in our understanding about host immune responses during malaria have been made, opening up opportunities to generate long-lasting antiparasitic immunity through vaccination or immune therapy. However, there is still much debate over which immune cell populations contribute to immunity to malaria, including innate lymphocytes that comprise recently identified innate lymphoid cells (ILCs) and better known innate-like T cell subsets. Here, we review research on these immune cell subsets and discuss whether they have any important roles in immunity to malaria or if they are redundant.}, } @article {pmid30579696, year = {2018}, author = {Ambrosino, L and Vassalli, QA and D'Agostino, Y and Esposito, R and Cetrangolo, V and Caputi, L and Amoroso, A and Aniello, F and D'Aniello, S and Chatzigeorgiou, M and Chiusano, ML and Locascio, A}, title = {Functional conserved non-coding elements among tunicates and chordates.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.012}, pmid = {30579696}, issn = {1095-564X}, abstract = {Non-coding regions with dozens to several hundred base pairs of extreme conservation have been found in all metazoan genomes. The distribution of these conserved non-coding elements (CNE) within and across genomes has suggested that many of them may have roles as transcriptional regulatory elements. A combination of bioinformatics and experimental approaches can be used to identify CNEs with regulatory activity in phylogenetically distant species. Nevertheless, the high divergent rate of genomic sequences of several organisms, such as tunicates, complicates the characterization of these conserved elements and very few examples really may prove their functional activity. We used a comparative approach to facilitate the identification of CNEs among distantly related or highly divergent species and experimentally demonstrated the functional significance of these novel CNEs. We first experimentally tested, in C. robusta and D. rerio transgenic embryos, the regulatory activity of conserved elements associated to genes involved in developmental control among different chordates (Homo sapiens and Danio rerio for vertebrates, Ciona robusta and Ciona savignyi for tunicates and Branchiostoma floridae for cephalochordates). Once demonstrated the cross-species functional conservation of these CNEs, the same gene loci were used as references to locate homologous regions and possible CNEs in available tunicate genomes. Comparison of tunicate-specific and chordate-specific CNEs revealed absence of conservation of the regulatory elements in spite of conservation of regulatory patterns, likely due to evolutionary specification of the respective developmental networks. This result highlights the importance of an integrative in-silico/in-vivo approach to CNEs investigation, encompassing both bioinformatics, essential for putative CNEs identification, and laboratory experiments, pivotal for the understanding of CNEs functionality.}, } @article {pmid30579360, year = {2018}, author = {Keller, A and Brandel, A and Becker, MC and Balles, R and Abdelmohsen, UR and Ankenbrand, MJ and Sickel, W}, title = {Wild bees and their nests host Paenibacillus bacteria with functional potential of avail.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {229}, doi = {10.1186/s40168-018-0614-1}, pmid = {30579360}, issn = {2049-2618}, support = {University of Würzburg funding programme Open Access Publishing//Deutsche Forschungsgemeinschaft/ ; KE1743/4-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: In previous studies, the gram-positive firmicute genus Paenibacillus was found with significant abundances in nests of wild solitary bees. Paenibacillus larvae is well-known for beekeepers as a severe pathogen causing the fatal honey bee disease American foulbrood, and other members of the genus are either secondary invaders of European foulbrood or considered a threat to honey bees. We thus investigated whether Paenibacillus is a common bacterium associated with various wild bees and hence poses a latent threat to honey bees visiting the same flowers.

RESULTS: We collected 202 samples from 82 individuals or nests of 13 bee species at the same location and screened each for Paenibacillus using high-throughput sequencing-based 16S metabarcoding. We then isolated the identified strain Paenibacillus MBD-MB06 from a solitary bee nest and sequenced its genome. We did find conserved toxin genes and such encoding for chitin-binding proteins, yet none specifically related to foulbrood virulence or chitinases. Phylogenomic analysis revealed a closer relationship to strains of root-associated Paenibacillus rather than strains causing foulbrood or other accompanying diseases. We found anti-microbial evidence within the genome, confirmed by experimental bioassays with strong growth inhibition of selected fungi as well as gram-positive and gram-negative bacteria.

CONCLUSIONS: The isolated wild bee associate Paenibacillus MBD-MB06 is a common, but irregularly occurring part of wild bee microbiomes, present on adult body surfaces and guts and within nests especially in megachilids. It was phylogenetically and functionally distinct from harmful members causing honey bee colony diseases, although it shared few conserved proteins putatively toxic to insects that might indicate ancestral predisposition for the evolution of insect pathogens within the group. By contrast, our strain showed anti-microbial capabilities and the genome further indicates abilities for chitin-binding and biofilm-forming, suggesting it is likely a useful associate to avoid fungal penetration of the bee cuticula and a beneficial inhabitant of nests to repress fungal threats in humid and nutrient-rich environments of wild bee nests.}, } @article {pmid30579350, year = {2018}, author = {Mortensen, MS and Hebbelstrup Jensen, B and Williams, J and Brejnrod, AD and O'Brien Andersen, L and Röser, D and Andreassen, BU and Petersen, AM and Stensvold, CR and Sørensen, SJ and Krogfelt, KA}, title = {Stability and resilience of the intestinal microbiota in children in daycare - a 12 month cohort study.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {223}, doi = {10.1186/s12866-018-1367-5}, pmid = {30579350}, issn = {1471-2180}, support = {2101-07-0023//Strategiske Forskningsråd/ ; }, abstract = {BACKGROUND: We performed a 12-month cohort study of the stability and resilience of the intestinal microbiota of healthy children in daycare in Denmark in relation to diarrheal events and exposure to known risk factors for gastrointestinal health such as travelling and antibiotic use. In addition, we analyzed how gut microbiota recover from such exposures.

RESULTS: We monitored 32 children in daycare aged 1-6 years. Fecal samples were submitted every second month during a one-year observational period. Information regarding exposures and diarrheal episodes was obtained through questionnaires. Bacterial communities were identified using 16S rRNA gene sequencing. The core microbiota (mean abundance > 95%) dominated the intestinal microbiota, and none of the tested exposures (diarrheal events, travel, antibiotic use) were associated with decreases in the relative abundance of the core microbiota. Samples exhibited lower intra-individual variation than inter-individual variation. Half of all the variation between samples was explained by which child a sample originated from. Age explained 7.6-9.6% of the variation, while traveling, diarrheal events, and antibiotic use explained minor parts of the beta diversity. We found an age-dependent increase of alpha diversity in children aged 1-3 years, and while diarrheal events caused a decrease in alpha diversity, a recovery time of 40-45 days was observed. Among children having had a diarrheal event, we observed a 10x higher relative abundance of Prevotella. After travelling, a higher abundance of two Bacteroides species and 40% less Lachnospiraceae were seen. Antibiotic use did not correlate with changes in the abundance of any bacteria.

CONCLUSION: We present data showing that Danish children in daycare have stable intestinal microbiota, resilient to the exposures investigated. An early age-dependent increase in the diversity was demonstrated. Diarrheal episodes decreased alpha diversity with an estimated recovery time of 40-45 days.}, } @article {pmid30579332, year = {2018}, author = {Getachew, B and Aubee, JI and Schottenfeld, RS and Csoka, AB and Thompson, KM and Tizabi, Y}, title = {Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {222}, doi = {10.1186/s12866-018-1373-7}, pmid = {30579332}, issn = {1471-2180}, support = {R03AA022479//National Institute on Alcohol Abuse and Alcoholism/ ; R21AG047474//National Institute on Aging/ ; }, abstract = {BACKGROUND: Appreciable evidence suggest that dysbiosis in microbiota, reflected in gut microbial imbalance plays a key role in the pathogenesis of neuropsychiatric disorders including depression and inflammatory diseases. Recently, the antidepressant properties of ketamine have gained prominence due to its fast and long lasting effects. Additional uses for ketamine in inflammatory disorders such as irritable bowel syndrome have been suggested. However, ketamine's exact mechanism of action and potential effects on microbiome is not known. Here, we examined the effects of low dose ketamine, known to induce antidepressant effects, on stool microbiome profile in adult male Wistar rats. Animals (5/group) were injected intraperitoneally with ketamine (2.5 mg/kg) or saline, daily for 7 days and sacrificed on day 8 when intestinal stools were collected and stored at - 80 °C. DNA was extracted from the samples and the 16 S rRNA gene-based microbiota analysis was performed using 16S Metagenomics application.

RESULTS: At genus-level, ketamine strikingly amplified Lactobacillus, Turicibacter and Sarcina by 3.3, 26 and 42 fold, respectively. Conversely, opportunistic pathogens Mucispirillum and Ruminococcus were reduced by approximately 2.6 and 26 fold, respectively, in ketamine group. Low levels of Lactobacillus and Turicibacter are associated with various disorders including depression and administration of certain species of Lactobacillus ameliorates depressive-like behavior in animal models. Hence, some of the antidepressant effects of ketamine might be mediated through its interaction with these gut bacteria. Additionally, high level of Ruminococcus is positively associated with the severity of irritable bowel syndrome (IBS), and some species of Mucispirillum have been associated with intestinal inflammation. Indirect evidence of anti-inflammatory role of Sarcina has been documented. Hence, some of the anti-inflammatory effects of ketamine and its usefulness in specific inflammatory diseases including IBS may be mediated through its interaction with these latter bacteria.

CONCLUSION: Our data suggest that at least some of the antidepressant and anti-inflammatory effects of daily ketamine treatment for 7 days may be mediated via its interaction with specific gut bacteria. These findings further validate the usefulness of microbiome as a target for therapeutic intervention and call for more detailed investigation of microbiome interaction with central mediators of mood and/or inflammatory disorders.}, } @article {pmid30579326, year = {2018}, author = {Li, S and Zhong, M and Dong, X and Jiang, X and Xu, Y and Sun, Y and Cheng, F and Li, DZ and Tang, K and Wang, S and Dai, S and Hu, JY}, title = {Comparative transcriptomics identifies patterns of selection in roses.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {371}, doi = {10.1186/s12870-018-1585-x}, pmid = {30579326}, issn = {1471-2229}, support = {31660583//National Natural Science Foundation of China/ ; 31570311//National Natural Science Foundation of China/ ; 31501034//National Natural Science Foundation of China/ ; 292015312D11035//CAS Pioneer Hundred Talents Program/ ; 000000//Key Laboratory for Plant Diversity and Biogeography of East Asia (CAS)/ ; 000000//Yunnan Recruitment Program of Experts in Science/ ; }, abstract = {BACKGROUND: Roses are important plants for human beings with pivotal economical and biological traits like continuous flowering, flower architecture, color and scent. Due to frequent hybridization and high genome heterozygosity, classification of roses and their relatives remains a big challenge.

RESULTS: Here, to identify potential markers for phylogenetic reconstruction and to reveal the patterns of natural selection in roses, we generated sets of high quality and comprehensive reference transcriptomes for Rosa chinensis 'Old Blush' (OB) and R. wichuriana 'Basye's Thornless' (BT), two species exhibiting contrasted traits of high economical importance. The assembled reference transcriptomes showed transcripts N50 above 2000 bp. Two roses shared about 10,073 transcripts (N50 = 2282 bp), in which a set of 5959 transcripts was conserved within genera of Rosa. Further comparison with species in Rosaceae identified 4447 transcripts being common (Rosaceae-common) in Rosa, Malus, Prunus, Rubus, and Fragaria, while a pool of 164 transcripts being specific for roses (Rosa-specific). Among the Rosaceae-common transcripts, 409 transcripts showed a signature of positive selection and a clustered expression in different tissues. Interestingly, nine of these rapidly evolving genes were related to DNA damage repair and responses to environmental stimulus, a potential associated with genome confliction post hybridization. Coincident with this fast evolution pattern in rose genes, 24 F-box and four TMV resistant proteins were significantly enriched in the Rosa-specific genes.

CONCLUSIONS: We expect that these Rosaceae-common and Rosa-specific transcripts should facilitate the phylogenetic analysis of Rosaceae plants as well as investigations of Rosa-specific biology. The data reported here could provide fundamental genomic tools and knowledge critical for understanding the biology and domestication of roses and for roses breeding.}, } @article {pmid30578761, year = {2018}, author = {Jalvy, S and Veschambre, P and Fédou, S and Rezvani, HR and Thézé, N and Thiébaud, P}, title = {Leukemia inhibitory factor signaling in Xenopus embryo: Insights from gain of function analysis and dominant negative mutant of the receptor.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.020}, pmid = {30578761}, issn = {1095-564X}, abstract = {Leukemia inhibitory factor (LIF) is a cytokine member of the interleukin 6 family (IL6) of cytokines. It signals through a heterodimer receptor complex that consists of the LIF receptor (or LIFR formerly known as gp190) and the Interleukin 6 signal transducer (or IL6ST formerly known as gp130). LIF signaling is mediated mainly by signal transducer and activator of transcription 3 (STAT3) and has a wide variety of biological activities with pleiotropic effects on many cell types and organs among which are stem cell renewal and implantation process in mammalian embryo. Despite the wealth of data on LIF in mammalian cells, there is a paucity of information on its functions in lower vertebrates. Here, we provide information on the status and the function of LIF signaling in Xenopus amphibian. The IL6 cytokine family is highly conserved in Xenopus genome both at ligands and receptors levels. All cytokines and receptors of the family, except oncostatin M (OSM) and IL27, can be identified in the genome including the orthologs of LIF, cardiotrophin 1 (CTF1), ciliary neurotrophic factor (CNTF), cardiotrophin like cytokine factor 1 (CLCF1), LIFR, IL6ST, IL6R, IL11RA and CNTFR. Lif mRNA is zygotically expressed after midblastula transition while lifr and il6st are maternally expressed. We have investigated the functions of LIF in Xenopus early development with a gain-of-function analysis combined to the use of a dominant negative form of the receptor. The overexpression of Xenopus lif in embryo activates STAT3 phosphorylation and induces a dramatic phenotype where embryos are ventralised and show a reduction of anterior structures with microcephaly. This results mainly from BMP signal stimulation and antagonism towards IGF signals. In addition, most embryos develop tumor-like cell masses according to both autonomous and non-autonomous processes. Through the use of a dominant negative form of the receptor, we demonstrate for the first time that a functional LIF signaling is required for normal vertebrate kidney development. Owing to its experimental advantages, the Xenopus embryo constitutes a useful model to identify the molecular actors that may account for the pleiotropic functions of LIF and their role in vertebrate development.}, } @article {pmid30578760, year = {2018}, author = {Aramaki, T and Kondo, S}, title = {Method for disarranging the pigment pattern of zebrafish by optogenetics.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.019}, pmid = {30578760}, issn = {1095-564X}, abstract = {To investigate the spatiotemporal dynamics of skin pattern formation, we developed a simple method for artificially disarranging the placement of all three pigment cell types in the body trunk of zebrafish (Danio rerio). We generated transgenic fish with melanophores that ectopically expressed a variant of channelrhodopsin-2 (ChR2). Blue light (BL) irradiation induced melanophore depolarization and random migration; the latter resulted in the disarrangement of the two other pigment cell types (xanthophores and iridophores). This BL disarrangement (BLD) method was effective in both young and adult fish, but it did not affect the initial placement of pigment cells in juvenile fish (approximately 5 weeks post-fertilization). Irradiation with BL was not harmful to cells, and the patterning process immediately resumed when BL was switched off. Using the BLD method, we demonstrated that interactions between pigment cells determined stripe width in the absence of any pre-set positional cues, while the initial horizontal alignment of iridophores determined their directionality. The BLD method can be adapted to any zebrafish skin-pattern mutant, providing a novel tool for analyzing pattern formation mechanisms under a variety of conditions and facilitating further study in this field.}, } @article {pmid30578589, year = {2018}, author = {Mulholland, MM and Neal Webb, SJ}, title = {Primatologists: Around the world in 11 days.}, journal = {Evolutionary anthropology}, volume = {}, number = {}, pages = {}, doi = {10.1002/evan.21757}, pmid = {30578589}, issn = {1520-6505}, } @article {pmid30578418, year = {2019}, author = {Giri, A and Hellwege, JN and Keaton, JM and Park, J and Qiu, C and Warren, HR and Torstenson, ES and Kovesdy, CP and Sun, YV and Wilson, OD and Robinson-Cohen, C and Roumie, CL and Chung, CP and Birdwell, KA and Damrauer, SM and DuVall, SL and Klarin, D and Cho, K and Wang, Y and Evangelou, E and Cabrera, CP and Wain, LV and Shrestha, R and Mautz, BS and Akwo, EA and Sargurupremraj, M and Debette, S and Boehnke, M and Scott, LJ and Luan, J and Zhao, JH and Willems, SM and Thériault, S and Shah, N and Oldmeadow, C and Almgren, P and Li-Gao, R and Verweij, N and Boutin, TS and Mangino, M and Ntalla, I and Feofanova, E and Surendran, P and Cook, JP and Karthikeyan, S and Lahrouchi, N and Liu, C and Sepúlveda, N and Richardson, TG and Kraja, A and Amouyel, P and Farrall, M and Poulter, NR and , and , and , and Laakso, M and Zeggini, E and Sever, P and Scott, RA and Langenberg, C and Wareham, NJ and Conen, D and Palmer, CNA and Attia, J and Chasman, DI and Ridker, PM and Melander, O and Mook-Kanamori, DO and Harst, PV and Cucca, F and Schlessinger, D and Hayward, C and Spector, TD and Jarvelin, MR and Hennig, BJ and Timpson, NJ and Wei, WQ and Smith, JC and Xu, Y and Matheny, ME and Siew, EE and Lindgren, C and Herzig, KH and Dedoussis, G and Denny, JC and Psaty, BM and Howson, JMM and Munroe, PB and Newton-Cheh, C and Caulfield, MJ and Elliott, P and Gaziano, JM and Concato, J and Wilson, PWF and Tsao, PS and Velez Edwards, DR and Susztak, K and , and O'Donnell, CJ and Hung, AM and Edwards, TL}, title = {Trans-ethnic association study of blood pressure determinants in over 750,000 individuals.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {51-62}, doi = {10.1038/s41588-018-0303-9}, pmid = {30578418}, issn = {1546-1718}, support = {R01 HL133786/HL/NHLBI NIH HHS/United States ; R21 HL121429/HL/NHLBI NIH HHS/United States ; T32 CA160056/CA/NCI NIH HHS/United States ; }, abstract = {In this trans-ethnic multi-omic study, we reinterpret the genetic architecture of blood pressure to identify genes, tissues, phenomes and medication contexts of blood pressure homeostasis. We discovered 208 novel common blood pressure SNPs and 53 rare variants in genome-wide association studies of systolic, diastolic and pulse pressure in up to 776,078 participants from the Million Veteran Program (MVP) and collaborating studies, with analysis of the blood pressure clinical phenome in MVP. Our transcriptome-wide association study detected 4,043 blood pressure associations with genetically predicted gene expression of 840 genes in 45 tissues, and mouse renal single-cell RNA sequencing identified upregulated blood pressure genes in kidney tubule cells.}, } @article {pmid30578417, year = {2019}, author = {Verbitsky, M and Westland, R and Perez, A and Kiryluk, K and Liu, Q and Krithivasan, P and Mitrotti, A and Fasel, DA and Batourina, E and Sampson, MG and Bodria, M and Werth, M and Kao, C and Martino, J and Capone, VP and Vivante, A and Shril, S and Kil, BH and Marasà, M and Zhang, JY and Na, YJ and Lim, TY and Ahram, D and Weng, PL and Heinzen, EL and Carrea, A and Piaggio, G and Gesualdo, L and Manca, V and Masnata, G and Gigante, M and Cusi, D and Izzi, C and Scolari, F and van Wijk, JAE and Saraga, M and Santoro, D and Conti, G and Zamboli, P and White, H and Drozdz, D and Zachwieja, K and Miklaszewska, M and Tkaczyk, M and Tomczyk, D and Krakowska, A and Sikora, P and Jarmoliński, T and Borszewska-Kornacka, MK and Pawluch, R and Szczepanska, M and Adamczyk, P and Mizerska-Wasiak, M and Krzemien, G and Szmigielska, A and Zaniew, M and Dobson, MG and Darlow, JM and Puri, P and Barton, DE and Furth, SL and Warady, BA and Gucev, Z and Lozanovski, VJ and Tasic, V and Pisani, I and Allegri, L and Rodas, LM and Campistol, JM and Jeanpierre, C and Alam, S and Casale, P and Wong, CS and Lin, F and Miranda, DM and Oliveira, EA and Simões-E-Silva, AC and Barasch, JM and Levy, B and Wu, N and Hildebrandt, F and Ghiggeri, GM and Latos-Bielenska, A and Materna-Kiryluk, A and Zhang, F and Hakonarson, H and Papaioannou, VE and Mendelsohn, CL and Gharavi, AG and Sanna-Cherchi, S}, title = {The copy number variation landscape of congenital anomalies of the kidney and urinary tract.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {117-127}, doi = {10.1038/s41588-018-0281-y}, pmid = {30578417}, issn = {1546-1718}, support = {R01 DK088767/DK/NIDDK NIH HHS/United States ; }, abstract = {Congenital anomalies of the kidney and urinary tract (CAKUT) are a major cause of pediatric kidney failure. We performed a genome-wide analysis of copy number variants (CNVs) in 2,824 cases and 21,498 controls. Affected individuals carried a significant burden of rare exonic (that is, affecting coding regions) CNVs and were enriched for known genomic disorders (GD). Kidney anomaly (KA) cases were most enriched for exonic CNVs, encompassing GD-CNVs and novel deletions; obstructive uropathy (OU) had a lower CNV burden and an intermediate prevalence of GD-CNVs; and vesicoureteral reflux (VUR) had the fewest GD-CNVs but was enriched for novel exonic CNVs, particularly duplications. Six loci (1q21, 4p16.1-p16.3, 16p11.2, 16p13.11, 17q12 and 22q11.2) accounted for 65% of patients with GD-CNVs. Deletions at 17q12, 4p16.1-p16.3 and 22q11.2 were specific for KA; the 16p11.2 locus showed extensive pleiotropy. Using a multidisciplinary approach, we identified TBX6 as a driver for the CAKUT subphenotypes in the 16p11.2 microdeletion syndrome.}, } @article {pmid30578322, year = {2019}, author = {Spinazzi, M and Radaelli, E and Horré, K and Arranz, AM and Gounko, NV and Agostinis, P and Maia, TM and Impens, F and Morais, VA and Lopez-Lluch, G and Serneels, L and Navas, P and De Strooper, B}, title = {PARL deficiency in mouse causes Complex III defects, coenzyme Q depletion, and Leigh-like syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {277-286}, doi = {10.1073/pnas.1811938116}, pmid = {30578322}, issn = {1091-6490}, abstract = {The mitochondrial intramembrane rhomboid protease PARL has been implicated in diverse functions in vitro, but its physiological role in vivo remains unclear. Here we show that Parl ablation in mouse causes a necrotizing encephalomyelopathy similar to Leigh syndrome, a mitochondrial disease characterized by disrupted energy production. Mice with conditional PARL deficiency in the nervous system, but not in muscle, develop a similar phenotype as germline Parl KOs, demonstrating the vital role of PARL in neurological homeostasis. Genetic modification of two major PARL substrates, PINK1 and PGAM5, do not modify this severe neurological phenotype. Parl-/- brain mitochondria are affected by progressive ultrastructural changes and by defects in Complex III (CIII) activity, coenzyme Q (CoQ) biosynthesis, and mitochondrial calcium metabolism. PARL is necessary for the stable expression of TTC19, which is required for CIII activity, and of COQ4, which is essential in CoQ biosynthesis. Thus, PARL plays a previously overlooked constitutive role in the maintenance of the respiratory chain in the nervous system, and its deficiency causes progressive mitochondrial dysfunction and structural abnormalities leading to neuronal necrosis and Leigh-like syndrome.}, } @article {pmid30578321, year = {2019}, author = {Wytock, TP and Motter, AE}, title = {Predicting growth rate from gene expression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {367-372}, doi = {10.1073/pnas.1808080116}, pmid = {30578321}, issn = {1091-6490}, abstract = {Growth rate is one of the most important and most complex phenotypic characteristics of unicellular microorganisms, which determines the genetic mutations that dominate at the population level, and ultimately whether the population will survive. Translating changes at the genetic level to their growth-rate consequences remains a subject of intense interest, since such a mapping could rationally direct experiments to optimize antibiotic efficacy or bioreactor productivity. In this work, we directly map transcriptional profiles to growth rates by gathering published gene-expression data from Escherichia coli and Saccharomyces cerevisiae with corresponding growth-rate measurements. Using a machine-learning technique called k-nearest-neighbors regression, we build a model which predicts growth rate from gene expression. By exploiting the correlated nature of gene expression and sparsifying the model, we capture 81% of the variance in growth rate of the E. coli dataset, while reducing the number of features from >4,000 to 9. In S. cerevisiae, we account for 89% of the variance in growth rate, while reducing from >5,500 dimensions to 18. Such a model provides a basis for selecting successful strategies from among the combinatorial number of experimental possibilities when attempting to optimize complex phenotypic traits like growth rate.}, } @article {pmid30578320, year = {2019}, author = {Mele, EJ}, title = {Dowsing for nodal lines in a topological semimetal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {4}, pages = {1084-1086}, doi = {10.1073/pnas.1820331116}, pmid = {30578320}, issn = {1091-6490}, } @article {pmid30578319, year = {2019}, author = {Zadra, G and Ribeiro, CF and Chetta, P and Ho, Y and Cacciatore, S and Gao, X and Syamala, S and Bango, C and Photopoulos, C and Huang, Y and Tyekucheva, S and Bastos, DC and Tchaicha, J and Lawney, B and Uo, T and D'Anello, L and Csibi, A and Kalekar, R and Larimer, B and Ellis, L and Butler, LM and Morrissey, C and McGovern, K and Palombella, VJ and Kutok, JL and Mahmood, U and Bosari, S and Adams, J and Peluso, S and Dehm, SM and Plymate, SR and Loda, M}, title = {Inhibition of de novo lipogenesis targets androgen receptor signaling in castration-resistant prostate cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {631-640}, doi = {10.1073/pnas.1808834116}, pmid = {30578319}, issn = {1091-6490}, abstract = {A hallmark of prostate cancer progression is dysregulation of lipid metabolism via overexpression of fatty acid synthase (FASN), a key enzyme in de novo fatty acid synthesis. Metastatic castration-resistant prostate cancer (mCRPC) develops resistance to inhibitors of androgen receptor (AR) signaling through a variety of mechanisms, including the emergence of the constitutively active AR variant V7 (AR-V7). Here, we developed an FASN inhibitor (IPI-9119) and demonstrated that selective FASN inhibition antagonizes CRPC growth through metabolic reprogramming and results in reduced protein expression and transcriptional activity of both full-length AR (AR-FL) and AR-V7. Activation of the reticulum endoplasmic stress response resulting in reduced protein synthesis was involved in IPI-9119-mediated inhibition of the AR pathway. In vivo, IPI-9119 reduced growth of AR-V7-driven CRPC xenografts and human mCRPC-derived organoids and enhanced the efficacy of enzalutamide in CRPC cells. In human mCRPC, both FASN and AR-FL were detected in 87% of metastases. AR-V7 was found in 39% of bone metastases and consistently coexpressed with FASN. In patients treated with enzalutamide and/or abiraterone FASN/AR-V7 double-positive metastases were found in 77% of cases. These findings provide a compelling rationale for the use of FASN inhibitors in mCRPCs, including those overexpressing AR-V7.}, } @article {pmid30578318, year = {2019}, author = {Rappuoli, R and De Gregorio, E and Costantino, P}, title = {On the mechanisms of conjugate vaccines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {14-16}, doi = {10.1073/pnas.1819612116}, pmid = {30578318}, issn = {1091-6490}, } @article {pmid30578150, year = {2018}, author = {Karvonen, A and Jokela, J and Laine, AL}, title = {Importance of Sequence and Timing in Parasite Coinfections.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.007}, pmid = {30578150}, issn = {1471-5007}, abstract = {Coinfections by multiple parasites predominate in the wild. Interactions between parasites can be antagonistic, neutral, or facilitative, and they can have significant implications for epidemiology, disease dynamics, and evolution of virulence. Coinfections commonly result from sequential exposure of hosts to different parasites. We argue that the sequential nature of coinfections is important for the consequences of infection in both natural and man-made environments. Coinfections accumulate during host lifespan, determining the structure of the parasite infracommunity. Interactions within the parasite community and their joint effect on the host individual potentially shape evolution of parasite life-history traits and transmission biology. Overall, sequential coinfections have the potential to change evolutionary and epidemiological outcomes of host-parasite interactions widely across plant and animal systems.}, } @article {pmid30578149, year = {2019}, author = {Bailey, F and Eaton, J and Jidda, M and van Brakel, WH and Addiss, DG and Molyneux, DH}, title = {Neglected Tropical Diseases and Mental Health: Progress, Partnerships, and Integration.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {23-31}, doi = {10.1016/j.pt.2018.11.001}, pmid = {30578149}, issn = {1471-5007}, abstract = {Neglected tropical diseases (NTDs) are increasingly recognised as major drivers of psychosocial morbidity in affected individuals and their caregivers. Nevertheless, there has remained a lack of prioritisation at the policy level of some of the most stigmatising and chronic NTDs, with subsequent under-representation within NTD programmes. In response, the Neglected Tropical Disease/Non-Governmental Organization/Network (NNN) has established a Mental Wellbeing and Stigma Task Group (MWS) to address these issues through a comprehensive research agenda. In our article, we highlight the progress in understanding the scope of the mental health impact of NTDs and the innovative practice emerging in this area. Finally, we examine opportunities for integration of mental and physical health for individuals with NTDs.}, } @article {pmid30577989, year = {2019}, author = {See, YX and Wang, BZ and Fullwood, MJ}, title = {Chromatin Interactions and Regulatory Elements in Cancer: From Bench to Bedside.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {145-158}, doi = {10.1016/j.tig.2018.11.007}, pmid = {30577989}, issn = {0168-9525}, abstract = {Chromatin interactions regulate gene expression by bringing distal regulatory elements, such as super-enhancers, to promoters in close spatial proximity. It has been recognized that in cancer, chromatin interactions can be dysregulated, leading to aberrant oncogene expression. Chromatin interactions may potentially serve as biomarkers, or be modulated via CRISPR therapy and small molecule inhibitors against transcription. However, these methods face challenges that must be resolved and raise questions for further research. Understanding chromatin interactions is essential for safety aspects of anticancer therapies, such as the mechanism of action of epigenetic regulators and transcription factors in cancer, and potential off-target effects arising from targeting super-enhancers and promoters. In this review article, we discuss how chromatin interactions and regulatory elements may become dysregulated in cancer, potential methods to target them for clinical therapy, and outline outstanding questions that require addressing before epigenetic therapies can translate to the clinic safely and effectively.}, } @article {pmid30577974, year = {2018}, author = {Ashraf, U and Benoit-Pilven, C and Lacroix, V and Navratil, V and Naffakh, N}, title = {Advances in Analyzing Virus-Induced Alterations of Host Cell Splicing.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.11.004}, pmid = {30577974}, issn = {1878-4380}, abstract = {Alteration of host cell splicing is a common feature of many viral infections which is underappreciated because of the complexity and technical difficulty of studying alternative splicing (AS) regulation. Recent advances in RNA sequencing technologies revealed that up to several hundreds of host genes can show altered mRNA splicing upon viral infection. The observed changes in AS events can be either a direct consequence of viral manipulation of the host splicing machinery or result indirectly from the virus-induced innate immune response or cellular damage. Analysis at a higher resolution with single-cell RNAseq, and at a higher scale with the integration of multiple omics data sets in a systems biology perspective, will be needed to further comprehend this complex facet of virus-host interactions.}, } @article {pmid30577884, year = {2018}, author = {van Agteren, J and Iasiello, M and Lo, L}, title = {Improving the wellbeing and resilience of health services staff via psychological skills training.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {924}, doi = {10.1186/s13104-018-4034-x}, pmid = {30577884}, issn = {1756-0500}, abstract = {OBJECTIVE: Health services staff work in a stressful environment, which can negatively impact their mental health and wellbeing, and as a result can affect psychosocial and professional functioning. The implementation of resilience training aims to provide staff with basic psychological skills to improve mental health outcomes. The aim of the current pre-post study was to determine the short-term effects of group-based resilience training on clinical and non-clinical medical staff's (n = 40) mental health outcomes.

RESULTS: The study showed statistically significant improvements in resilience (r = 0.51, p = 0.02) and wellbeing (d = 0.29, p = 0.001) from before to 1 month after the training. Participants with the lowest wellbeing and resilience scores at start of the training showed higher effect sizes compared to those with highest wellbeing and resilience scores, (r = 0.67 compared to r = - 0.36 for wellbeing scores and d = 0.92 compared to d = 0.24 for resilience scores); differences that point to particular impact of the training for people with the lowest baseline values. No significant changes in psychological distress as a result of depression, anxiety and stress were found. Brief implications of the findings for mental health and wellbeing interventions in the health services are discussed.}, } @article {pmid30577879, year = {2018}, author = {Das, A and Ianakiev, P and Baten, A and Nehleen, R and Ehsan, T and Ahmed, O and Islam, MR and Naser, MN and Marma, MS and Khan, H}, title = {Genome of Tenualosa ilisha from the river Padma, Bangladesh.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {921}, doi = {10.1186/s13104-018-4028-8}, pmid = {30577879}, issn = {1756-0500}, abstract = {OBJECTIVE: Hilsa shad (Tenualosa ilisha), is a popular fish of Bangladesh belonging to the Clupeidae family. An anadromous species, like the salmon and many other migratory fish, it is a unique species that lives in the sea and travels to freshwater rivers for spawning. During its entire life, Tenualosa ilisha migrates both from sea to freshwater and vice versa.

DATA DESCRIPTION: The genome of Tenualosa ilisha collected from the river Padma of Rajshahi, Bangladesh has been sequenced and its de novo hybrid assembly and structural annotations are being reported here. Illumina and PacBio sequencing platforms were used for high depth sequencing and the draft genome assembly was found to be 816 MB with N50 size of 188 kb. MAKER gene annotation tool predicted 31,254 gene models. Benchmarking Universal Single-Copy Orthologs refer 95% completeness of the assembled genome.}, } @article {pmid30577878, year = {2018}, author = {Tudorache, C and Slabbekoorn, H and Robbers, Y and Hin, E and Meijer, JH and Spaink, HP and Schaaf, MJM}, title = {Biological clock function is linked to proactive and reactive personality types.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {148}, doi = {10.1186/s12915-018-0618-0}, pmid = {30577878}, issn = {1741-7007}, abstract = {BACKGROUND: Many physiological processes in our body are controlled by the biological clock and show circadian rhythmicity. It is generally accepted that a robust rhythm is a prerequisite for optimal functioning and that a lack of rhythmicity can contribute to the pathogenesis of various diseases. Here, we tested in a heterogeneous laboratory zebrafish population whether and how variation in the rhythmicity of the biological clock is associated with the coping styles of individual animals, as assessed in a behavioural assay to reliably measure this along a continuum between proactive and reactive extremes.

RESULTS: Using RNA sequencing on brain samples, we demonstrated a prominent difference in the expression level of genes involved in the biological clock between proactive and reactive individuals. Subsequently, we tested whether this correlation between gene expression and coping style was due to a consistent change in the level of clock gene expression or to a phase shift or to altered amplitude of the circadian rhythm of gene expression. Our data show a remarkable individual variation in amplitude of the clock gene expression rhythms, which was also reflected in the fluctuating concentrations of melatonin and cortisol, and locomotor activity. This variation in rhythmicity showed a strong correlation with the coping style of the individual, ranging from robust rhythms with large amplitudes in proactive fish to a complete absence of rhythmicity in reactive fish. The rhythmicity of the proactive fish decreased when challenged with constant light conditions whereas the rhythmicity of reactive individuals was not altered.

CONCLUSION: These results shed new light on the role of the biological clock by demonstrating that large variation in circadian rhythmicity of individuals may occur within populations. The observed correlation between coping style and circadian rhythmicity suggests that the level of rhythmicity forms an integral part of proactive or reactive coping styles.}, } @article {pmid30577877, year = {2018}, author = {Hasnain, MG and Nath, P and Maruf, S and Nabi, SG and Hossain, AFMA and Ahmed, BN and Mondal, D and Basher, A}, title = {Amphotericin B deoxycholate for relapse visceral leishmaniasis in Bangladesh: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {918}, doi = {10.1186/s13104-018-4036-8}, pmid = {30577877}, issn = {1756-0500}, abstract = {OBJECTIVE: Based on studies in India (as there was no studies from outside India) amphotericin B deoxycholate has been considered as a backup drug for treatment of visceral leishmaniasis. However, treatment response and adverse effect to anti-leishmanial drugs may vary across different populations and in Bangladesh the effect to amphotericin B deoxycholate for treatment of visceral leishmaniasis is still unknown. Therefore, there is a need to explore cure rate and adverse effects to amphotericin B deoxycholate to justify its use on visceral leishmaniasis patients in Bangladesh.

RESULT: Here we report 34 visceral leishmaniasis patients who received treatment with amphotericin B deoxycholate in the Surya Kanta Kala-azar Research Centre from December 2011 to June 2015. The dose of the treatment was 1 mg/kg body weight for 15 days followed up until 12 months after treatment. Response to amphotericin B deoxycholate treatment was excellent as all 34 patients achieved a final cure. Hypokalaemia (47%), shivering (47%), vomiting (35%) and acidity (15%) were most common adverse events. However, we did not observe any serious adverse events. Amphotericin B deoxycholate for relapse visceral leishmaniasis was found to be highly effective and safe. Our study justified to include amphotericin B deoxycholate as a second line drug for visceral leishmaniasis in Bangladesh.}, } @article {pmid30577876, year = {2018}, author = {Animen, S and Lake, S and Mekuriaw, E}, title = {Utilization of intra uterine contraceptive device and associated factors among reproductive age group of family planning users in Han Health Center, Bahir Dar, North West Amhara, Ethiopia, 2018.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {922}, doi = {10.1186/s13104-018-4032-z}, pmid = {30577876}, issn = {1756-0500}, abstract = {OBJECTIVE: Aim was to assess utilization of IUCD and factors among family planning users in Han health center, Bahir Dar, Ethiopia, 2018. Two hundred forty-one participants were selected by Systematic sampling technique from June 10 to July 10, 2018. Logistic regression employed to assess association between variables with 95% CI and p value less than 0.05 was set association.

RESULTS: 32 (13.3%) used intrauterine contraceptive device. Age 35-49 [AOR = 5.38, 95% CI 1.02, - 28.49] women who could read and write [AOR = 4.64, 95% CI 1.45-14.87], who were primary [AOR = 8.08, 95% CI 2.19-29.76], who were secondary [AOR = 8.89, 95% CI 1.63-48.42] who were attended college and above [AOR = 21.24, 95% CI = 5.05-89.39] and who were counseled IUCD [AOR = 3.08, 95% CI 1.26-7.54] were significant factors. Therefore, to scale up the utilization of IUCD, counseling IUCD and expanding female education should be undertaken.}, } @article {pmid30577873, year = {2018}, author = {Dai, Y and Li, C and Pei, G and Dong, X and Ding, G and Zhao, Z and Li, Y and Jia, P}, title = {Multiple transcription factors contribute to inter-chromosomal interaction in yeast.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {140}, doi = {10.1186/s12918-018-0643-1}, pmid = {30577873}, issn = {1752-0509}, support = {R01 LM011177/LM/NLM NIH HHS/United States ; R01 LM012806/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Chromatin interactions medicated by genomic elements located throughout the genome play important roles in gene regulation and can be identified with the technologies such as high-throughput chromosome conformation capture (Hi-C), followed by next-generation sequencing. These techniques were wildly used to reveal the relative spatial disposition of chromatins in human, mouse and yeast. Unlike metazoan where CTCF plays major roles in mediating chromatin interactions, in yeast, the transcription factors (TFs) involved in this biological process are poorly known.

RESULTS: Here, we presented two computational approaches to estimate the TFs enriched in the chromatin physical inter-chromosomal interactions in yeast. Through the Chi-square method, we found TFs whose binding data are differentially distributed in different interaction groups, including Cin5, Stp1 and Sut1, whose binding data are negatively correlated with the chromosome spatial distance. A multivariate linear regression model was employed to estimate the potential contribution of different transcription factors against the physical distance of chromosomes. Rlr1, Set12 and Dig1 were found to be top positively participated in these chromosomal interactions. Ste12 was highlighted to be involved in gene reposition. Overall, we found 10 TFs enriched from both computational approaches, potentially to be involved in inter-chromosomal interactions.

CONCLUSIONS: No transcription factor (TF) in our study was found to have a dominant impact on the inter-chromosomal interaction as CTCF did in human or other metazoan, suggesting species without CTCF might have different regulatory systems in mediating inter-chromosomal interactions. In summary, we presented a systematic examination of TFs involved in chromatin interaction in yeast and the results provide candidate TFs for future studies.}, } @article {pmid30577868, year = {2018}, author = {Eze, UU and Ngoepe, EC and Anene, BM and Ezeokonkwo, RC and Nwosuh, C and Sabeta, CT}, title = {Detection of lyssavirus antigen and antibody levels among apparently healthy and suspected rabid dogs in South-Eastern Nigeria.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {920}, doi = {10.1186/s13104-018-4024-z}, pmid = {30577868}, issn = {1756-0500}, support = {IBR-36//Tertiary Education Trust Fund/ ; P10000029//ARC-OVI National Assets/ ; }, abstract = {OBJECTIVES: Domestic dogs are the main reservoir of rabies virus (RABV) infection in Nigeria, thus surveillance of rabies in dog populations is crucial in order to understand the patterns of spread of infection and ultimately devise an appropriate rabies control strategy. This study determined the presence of lyssavirus antigen in brain tissues and anti-rabies antibodies in sera of apparently healthy and suspected-rabid dogs slaughtered for human consumption at local markets in South-Eastern Nigeria.

RESULTS: Our findings demonstrated that 8.3% (n = 23) of brain tissues were lyssavirus positive and 2.5% (n = 25) of sera had rabies antibody levels as percentage blocking of 70% and above correlating with a cut-off value ≥ 0.5 IU/mL in the fluorescent antibody neutralization test. There was an inverse correlation between lyssavirus positivity and rabies antibody levels confirming that infected individuals most often do not develop virus neutralizing antibodies to the disease. The low percentage of rabies antibodies in this dog population suggests a susceptible population at high risk to RABV infection. These findings highlight a huge challenge to national rabies programs and subsequent elimination of the disease from Nigeria, considering that majority of dogs are confined to rural communal areas, where parenteral dog vaccination is not routinely undertaken.}, } @article {pmid30577853, year = {2018}, author = {Choi, WT and Tosun, M and Jeong, HH and Karakas, C and Semerci, F and Liu, Z and Maletić-Savatić, M}, title = {Metabolomics of mammalian brain reveals regional differences.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {127}, doi = {10.1186/s12918-018-0644-0}, pmid = {30577853}, issn = {1752-0509}, support = {P30 HD024064/HD/NICHD NIH HHS/United States ; R01 GM120033/GM/NIGMS NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: The mammalian brain is organized into regions with specific biological functions and properties. These regions have distinct transcriptomes, but little is known whether they may also differ in their metabolome. The metabolome, a collection of small molecules or metabolites, is at the intersection of the genetic background of a given cell or tissue and the environmental influences that affect it. Thus, the metabolome directly reflects information about the physiologic state of a biological system under a particular condition. The objective of this study was to investigate whether various brain regions have diverse metabolome profiles, similarly to their genetic diversity. The answer to this question would suggest that not only the genome but also the metabolome may contribute to the functional diversity of brain regions.

METHODS: We investigated the metabolome of four regions of the mouse brain that have very distinct functions: frontal cortex, hippocampus, cerebellum, and olfactory bulb. We utilized gas- and liquid- chromatography mass spectrometry platforms and identified 215 metabolites.

RESULTS: Principal component analysis, an unsupervised multivariate analysis, clustered each brain region based on its metabolome content, thus providing the unique metabolic profile of each region. A pathway-centric analysis indicated that olfactory bulb and cerebellum had most distinct metabolic profiles, while the cortical parenchyma and hippocampus were more similar in their metabolome content. Among the notable differences were distinct oxidative-anti-oxidative status and region-specific lipid profiles. Finally, a global metabolic connectivity analysis using the weighted correlation network analysis identified five hub metabolites that organized a unique metabolic network architecture within each examined brain region. These data indicate the diversity of global metabolome corresponding to specialized regional brain function and provide a new perspective on the underlying properties of brain regions.

CONCLUSION: In summary, we observed many differences in the metabolome among the various brain regions investigated. All four brain regions in our study had a unique metabolic signature, but the metabolites came from all categories and were not pathway-centric.}, } @article {pmid30577850, year = {2018}, author = {Ee Uli, J and Yong, CS and Yeap, SK and Alitheen, NB and Rovie-Ryan, JJ and Mat Isa, N and Tan, SG}, title = {RNA sequencing of kidney and liver transcriptome obtained from wild cynomolgus macaque (Macaca fascicularis) originating from Peninsular Malaysia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {923}, doi = {10.1186/s13104-018-4014-1}, pmid = {30577850}, issn = {1756-0500}, support = {GPIPB/2013/9413602//Research University Grant Scheme/ ; }, abstract = {OBJECTIVE: Using high-throughput RNA sequencing technology, this study aimed to sequence the transcriptome of kidney and liver tissues harvested from Peninsular Malaysia cynomolgus macaque (Macaca fascicularis). M. fascicularis are significant nonhuman primate models in the biomedical field, owing to the macaque's biological similarities with humans. The additional transcriptomic dataset will supplement the previously described Peninsular Malaysia M. fascicularis transcriptomes obtained in a past endeavour.

RESULTS: A total of 75,350,240 sequence reads were obtained via Hi-seq 2500 sequencing technology. A total of 5473 significant differentially expressed genes were called. Gene ontology functional categorisation showed that cellular process, catalytic activity, and cell part categories had the highest number of expressed genes, while the metabolic pathways category possessed the highest number of expressed genes in the KEGG pathway analysis. The additional sequence dataset will further enrich existing M. fascicularis transcriptome assemblies, and provide a dataset for further downstream studies.}, } @article {pmid30577846, year = {2018}, author = {Mallik, S and Zhao, Z}, title = {Identification of gene signatures from RNA-seq data using Pareto-optimal cluster algorithm.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {126}, doi = {10.1186/s12918-018-0650-2}, pmid = {30577846}, issn = {1752-0509}, support = {R01 LM012806/LM/NLM NIH HHS/United States ; R03 DE027393/DE/NIDCR NIH HHS/United States ; R03 DE028103/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Gene signatures are important to represent the molecular changes in the disease genomes or the cells in specific conditions, and have been often used to separate samples into different groups for better research or clinical treatment. While many methods and applications have been available in literature, there still lack powerful ones that can take account of the complex data and detect the most informative signatures.

METHODS: In this article, we present a new framework for identifying gene signatures using Pareto-optimal cluster size identification for RNA-seq data. We first performed pre-filtering steps and normalization, then utilized the empirical Bayes test in Limma package to identify the differentially expressed genes (DEGs). Next, we used a multi-objective optimization technique, "Multi-objective optimization for collecting cluster alternatives" (MOCCA in R package) on these DEGs to find Pareto-optimal cluster size, and then applied k-means clustering to the RNA-seq data based on the optimal cluster size. The best cluster was obtained through computing the average Spearman's Correlation Score among all the genes in pair-wise manner belonging to the module. The best cluster is treated as the signature for the respective disease or cellular condition.

RESULTS: We applied our framework to a cervical cancer RNA-seq dataset, which included 253 squamous cell carcinoma (SCC) samples and 22 adenocarcinoma (ADENO) samples. We identified a total of 582 DEGs by Limma analysis of SCC versus ADENO samples. Among them, 260 are up-regulated genes and 322 are down-regulated genes. Using MOCCA, we obtained seven Pareto-optimal clusters. The best cluster has a total of 35 DEGs consisting of all-upregulated genes. For validation, we ran PAMR (prediction analysis for microarrays) classifier on the selected best cluster, and assessed the classification performance. Our evaluation, measured by sensitivity, specificity, precision, and accuracy, showed high confidence.

CONCLUSIONS: Our framework identified a multi-objective based cluster that is treated as a signature that can classify the disease and control group of samples with higher classification performance (accuracy 0.935) for the corresponding disease. Our method is useful to find signature for any RNA-seq or microarray data.}, } @article {pmid30577841, year = {2018}, author = {Brewster, LM and Brewster, J}, title = {Historical data on cardiovascular health in Surinamese men.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {919}, doi = {10.1186/s13104-018-4030-1}, pmid = {30577841}, issn = {1756-0500}, support = {18CKF905PH20502//Creatine Kinase Foundation/ ; }, abstract = {OBJECTIVES: Cardiovascular risk factor burden was recently reported to be high in the Caribbean country Suriname. However, historical data for comparison were lacking. We report here rediscovered and hitherto unpublished aggregated data of what was apparently the first population study on measured blood pressure, diabetes, and cardiovascular health in men in this country, assessed in 1973. Data had been collected to raise the awareness of the local population for cardiovascular disease risk.

DATA DESCRIPTION: We provide a table of the cardiovascular risk profile, including exercise, smoking, hypertension and diabetes of 243 Surinamese adult non-institutionalized men living in an urban setting in the capital Paramaribo in 1973. These data may help understand the cardiovascular risk factor escalation of the population in time as well as aid in projections of future cardiovascular disease in this middle income country.}, } @article {pmid30577840, year = {2018}, author = {Yang, Q and Wu, J and Zhao, J and Xu, T and Zhao, Z and Song, X and Han, P}, title = {Circular RNA expression profiles during the differentiation of mouse neural stem cells.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {128}, doi = {10.1186/s12918-018-0651-1}, pmid = {30577840}, issn = {1752-0509}, support = {R01 LM012806/LM/NLM NIH HHS/United States ; R21 CA196508/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Circular RNAs (circRNAs) have recently been found to be expressed in human brain tissue, and many lines ofevidence indicate that circRNAs play regulatory roles in neurodevelopment. Proliferation and differentiation of neural stem cells (NSCs) are critical parts during development of central nervous system (CNS).To date, there have been no reports ofcircRNA expression profiles during the differentiation of mouse NSCs. We hypothesizethat circRNAs mayregulate gene expression in the proliferation anddifferentiation of NSCs.

RESULTS: In this study, we obtained NSCs from the wild-type C57BL/6 J mouse fetal cerebral cortex. We extracted total RNA from NSCs in different differentiation stagesand then performed RNA-seq. By analyzing the RNA-Seq data, we found 37circRNAs and 4182 mRNAs differentially expressedduringthe NSC differentiation. Gene Ontology (GO) enrichment analysis of thecognate linear genes of these circRNAsrevealed that some enriched GO terms were related to neural activity. Furthermore, we performed a co-expression network analysis of these differentially expressed circRNAs and mRNAs. The result suggested a stronger GO enrichmentin neural features for both the cognate linear genes of circRNAs and differentially expressed mRNAs.

CONCLUSION: We performed the first circRNA investigation during the differentiation of mouse NSCs. Wefound that12 circRNAs might have regulatory roles duringthe NSC differentiation, indicating that circRNAs might be modulated during NSC differentiation.Our network analysis suggested the possible complex circRNA-mRNA mechanisms during differentiation, and future experimental workis need to validate these possible mechanisms.}, } @article {pmid30577839, year = {2018}, author = {Wang, Y and Wang, J and Lin, H and Tang, X and Zhang, S and Li, L}, title = {Bidirectional long short-term memory with CRF for detecting biomedical event trigger in FastText semantic space.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {507}, doi = {10.1186/s12859-018-2543-1}, pmid = {30577839}, issn = {1471-2105}, mesh = {*Algorithms ; *Biomedical Research ; Information Storage and Retrieval ; Machine Learning ; *Semantics ; }, abstract = {BACKGROUND: In biomedical information extraction, event extraction plays a crucial role. Biological events are used to describe the dynamic effects or relationships between biological entities such as proteins and genes. Event extraction is generally divided into trigger detection and argument recognition. The performance of trigger detection directly affects the results of the event extraction. In general, the traditional method is used to address the trigger detection as a classification task, as well as the use of machine learning or rules method, which construct many features to improve the classification results. Moreover, the classification model only recognizes triggers composed of single words, whereas for multiple words, the result is unsatisfactory.

RESULTS: The corpus of our model is MLEE. If we were to only use the biomedical LSTM and CRF model without other features, the F-score would reach about 78.08%. Comparing entity to part of speech (POS), we find the entity features more conducive to the improvement of performance of detection, with the F-score potentially reaching about 80%. Furthermore, we also experiment on the other three corpora (BioNLP 2009, BioNLP 2011, and BioNLP 2013) to verify the generalization of our model. Hence, F-scores can reach more than 60%, which are better than the comparative experiments.

CONCLUSIONS: The trigger recognition method based on the sequence annotation model does not require initial complex feature engineering, and only requires a simple labeling mechanism to complete the training. Therefore, generalization of our model is better compared to other traditional models. Secondly, this method can identify multi-word triggers, thereby improving the F-scores of trigger recognition. Thirdly, details on the entity have a crucial impact on trigger detection. Finally, the combination of character-level word embedding and word-level word embedding provides increasingly effective information for the model; therefore, it is a key to the success of the experiment.}, } @article {pmid30577836, year = {2018}, author = {Chiu, YC and Hsiao, TH and Wang, LJ and Chen, Y and Shao, YJ}, title = {scdNet: a computational tool for single-cell differential network analysis.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {124}, doi = {10.1186/s12918-018-0652-0}, pmid = {30577836}, issn = {1752-0509}, support = {P30 CA054174/CA/NCI NIH HHS/United States ; UL1 RR025767/RR/NCRR NIH HHS/United States ; }, abstract = {BACKGROUND: Single-cell RNA sequencing (scRNA-Seq) is an emerging technology that has revolutionized the research of the tumor heterogeneity. However, the highly sparse data matrices generated by the technology have posed an obstacle to the analysis of differential gene regulatory networks.

RESULTS: Addressing the challenges, this study presents, as far as we know, the first bioinformatics tool for scRNA-Seq-based differential network analysis (scdNet). The tool features a sample size adjustment of gene-gene correlation, comparison of inter-state correlations, and construction of differential networks. A simulation analysis demonstrated the power of scdNet in the analyses of sparse scRNA-Seq data matrices, with low requirement on the sample size, high computation efficiency, and tolerance of sequencing noises. Applying the tool to analyze two datasets of single circulating tumor cells (CTCs) of prostate cancer and early mouse embryos, our data demonstrated that differential gene regulation plays crucial roles in anti-androgen resistance and early embryonic development.

CONCLUSIONS: Overall, the tool is widely applicable to datasets generated by the emerging technology to bring biological insights into tumor heterogeneity and other studies. MATLAB implementation of scdNet is available at https://github.com/ChenLabGCCRI/scdNet .}, } @article {pmid30577835, year = {2018}, author = {Chen, HH and Chiu, YC and Zhang, T and Zhang, S and Huang, Y and Chen, Y}, title = {GSAE: an autoencoder with embedded gene-set nodes for genomics functional characterization.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {142}, doi = {10.1186/s12918-018-0642-2}, pmid = {30577835}, issn = {1752-0509}, support = {P30 CA054174/CA/NCI NIH HHS/United States ; R01 GM113245/GM/NIGMS NIH HHS/United States ; UL1 RR025767/RR/NCRR NIH HHS/United States ; }, abstract = {BACKGROUND: Bioinformatics tools have been developed to interpret gene expression data at the gene set level, and these gene set based analyses improve the biologists' capability to discover functional relevance of their experiment design. While elucidating gene set individually, inter-gene sets association is rarely taken into consideration. Deep learning, an emerging machine learning technique in computational biology, can be used to generate an unbiased combination of gene set, and to determine the biological relevance and analysis consistency of these combining gene sets by leveraging large genomic data sets.

RESULTS: In this study, we proposed a gene superset autoencoder (GSAE), a multi-layer autoencoder model with the incorporation of a priori defined gene sets that retain the crucial biological features in the latent layer. We introduced the concept of the gene superset, an unbiased combination of gene sets with weights trained by the autoencoder, where each node in the latent layer is a superset. Trained with genomic data from TCGA and evaluated with their accompanying clinical parameters, we showed gene supersets' ability of discriminating tumor subtypes and their prognostic capability. We further demonstrated the biological relevance of the top component gene sets in the significant supersets.

CONCLUSIONS: Using autoencoder model and gene superset at its latent layer, we demonstrated that gene supersets retain sufficient biological information with respect to tumor subtypes and clinical prognostic significance. Superset also provides high reproducibility on survival analysis and accurate prediction for cancer subtypes.}, } @article {pmid30577823, year = {2018}, author = {Dversdal, RK and Gold, JA and Richards, MH and Chiovaro, JC and Iossi, KA and Mansoor, AM and Hunter, AJ and Desai, SS}, title = {A 5-day intensive curriculum for interns utilizing simulation and active-learning techniques: addressing domains important across internal medicine practice.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {916}, doi = {10.1186/s13104-018-4011-4}, pmid = {30577823}, issn = {1756-0500}, support = {R01 HS023793/HS/AHRQ HHS/United States ; R18 HS021637/HS/AHRQ HHS/United States ; R18HS021367//Agency for Healthcare Research and Quality/ ; }, abstract = {OBJECTIVE: Simulation-based learning strategies have demonstrated improved procedural competency, teamwork skills, and acute patient management skills in learners. "Boot camp" curricula have shown immediate and delayed performance in surgical and medical residents. We created a 5-day intensive, simulation and active learning-based curriculum for internal medicine interns to address perceived gaps in cognitive, affective and psychomotor domains. Intern confidence and self-perceived competence was assessed via survey before and after the curriculum, along with qualitative data.

RESULTS: A total of 33 interns completed the curriculum in 2014, 32 in 2015. Interns had a significant increase in confidence and self-perceived competence in procedural, cognitive and affective domains (all p values < .05).}, } @article {pmid30577822, year = {2018}, author = {Harder, T and Haller, S and Eckmanns, T and Seidel, J}, title = {Sepsis prediction during outbreaks at neonatal intensive care units through body surface screening for Gram-negative bacteria: systematic review and meta-analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {917}, doi = {10.1186/s13104-018-4033-y}, pmid = {30577822}, issn = {1756-0500}, abstract = {OBJECTIVE: This systematic review focusses on the prognostic accuracy of neonatal body surface screening during outbreaks caused by Gram-negative bacteria for prediction of sepsis. In a previous systematic review we reported that only limited evidence of very low quality exists regarding the predictive value of this screening under routine conditions. We aimed to investigate whether this is different in outbreak settings.

RESULTS: We identified five studies performed during outbreaks in three countries, comprising a total of 316 infants. All studies were at high risk of bias. In outbreak settings, pooled sensitivity of body surface screening to predict sepsis was 98% (95 CI 60 to 100%), while pooled specificity was 26% (95% CI 0.5 to 96%). Evidence quality was low for all outcomes. Extending a previously published systematic review, we show here that in contrast to routine settings sensitivity of body surface screening for sepsis prediction is very high, while specificity is still insufficient. Surface screening appears to be a useful component of bundles of interventions used during outbreaks, but the evidence base is still limited. PROSPERO Registration Number: CRD42016036664.}, } @article {pmid30577815, year = {2018}, author = {Chen, K and Yu, Y and Sun, K and Xiong, H and Yu, C and Chen, P and Chen, J and Gao, G and Zhu, A}, title = {The miRNAome of ramie (Boehmeria nivea L.): identification, expression, and potential roles of novel microRNAs in regulation of cadmium stress response.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {369}, doi = {10.1186/s12870-018-1561-5}, pmid = {30577815}, issn = {1471-2229}, support = {CAAS-ASTIP-2016-IBFC04//Science and Technology Innovation Project of the Chinese Academy of Agricultural Sciences/ ; CAAS-XTCX2016018//Technology Innovation Program in Chinese Academy of Agricultural Sciences/ ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) regulate numerous crucial abiotic stress processes in plants. However, information is limited on their involvement in cadmium (Cd) stress response and tolerance mechanisms in plants, including ramie (Boehmeria nivea L.) that produces a number of economic valuable as an important natural fibre crop and an ideal crop for Cd pollution remediation.

RESULTS: Four small RNA libraries of Cd-stressed and non-stressed leaves and roots of ramie were constructed. Using small RNA-sequencing, 73 novel miRNAs were identified. Genome-wide expression analysis revealed that a set of miRNAs was differentially regulated in response to Cd stress. In silico target prediction identified 426 potential miRNA targets that include several uptake or transport factors for heavy metal ions. The reliability of small RNA sequencing and the relationship between the expression levels of miRNAs and their target genes were confirmed by quantitative PCR (q-PCR). We showed that the expression patterns of miRNAs obtained by q-PCR were consistent with those obtained from small RNA sequencing. Moreover, we demonstrated that the expression of six randomly selected target genes was inversely related to that of their corresponding miRNAs, indicating that the miRNAs regulate Cd stress response in ramie.

CONCLUSIONS: This study enriches the number of Cd-responsive miRNAs and lays a foundation for the elucidation of the miRNA-mediated regulatory mechanism in ramie during Cd stress.}, } @article {pmid30577813, year = {2018}, author = {Xu, LY and Wang, LY and Wei, K and Tan, LQ and Su, JJ and Cheng, H}, title = {High-density SNP linkage map construction and QTL mapping for flavonoid-related traits in a tea plant (Camellia sinensis) using 2b-RAD sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {955}, doi = {10.1186/s12864-018-5291-8}, pmid = {30577813}, issn = {1471-2164}, support = {CARS-19//Earmarked Fund for China Agriculture Research System/ ; }, abstract = {BACKGROUND: Flavonoids are important components that confer upon tea plants a unique flavour and health functions. However, the traditional breeding method for selecting a cultivar with a high or unique flavonoid content is time consuming and labour intensive. High-density genetic map construction associated with quantitative trait locus (QTL) mapping provides an effective way to facilitate trait improvement in plant breeding. In this study, an F1 population (LJ43×BHZ) was genotyped using 2b-restriction site-associated DNA (2b-RAD) sequencing to obtain massive single nucleotide polymorphism (SNP) markers to construct a high-density genetic map for a tea plant. Furthermore, QTLs related to flavonoids were identified using our new genetic map.

RESULTS: A total of 13,446 polymorphic SNP markers were developed using 2b-RAD sequencing, and 4,463 of these markers were available for constructing the genetic linkage map. A 1,678.52-cM high-density map at an average interval of 0.40 cM with 4,217 markers, including 427 frameset simple sequence repeats (SSRs) and 3,800 novel SNPs, mapped into 15 linkage groups was successfully constructed. After QTL analysis, a total of 27 QTLs related to flavonoids or caffeine content (CAF) were mapped to 8 different linkage groups, LG01, LG03, LG06, LG08, LG10, LG11, LG12, and LG13, with an LOD from 3.14 to 39.54, constituting 7.5% to 42.8% of the phenotypic variation.

CONCLUSIONS: To our knowledge, the highest density genetic map ever reported was constructed since the largest mapping population of tea plants was adopted in present study. Moreover, novel QTLs related to flavonoids and CAF were identified based on the new high-density genetic map. In addition, two markers were located in candidate genes that may be involved in flavonoid metabolism. The present study provides valuable information for gene discovery, marker-assisted selection breeding and map-based cloning for functional genes that are related to flavonoid content in tea plants.}, } @article {pmid30577806, year = {2018}, author = {de Bruijn, S and Zhao, T and Muiño, JM and Schranz, EM and Angenent, GC and Kaufmann, K}, title = {PISTILLATA paralogs in Tarenaya hassleriana have diverged in interaction specificity.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {368}, doi = {10.1186/s12870-018-1574-0}, pmid = {30577806}, issn = {1471-2229}, support = {Msc talent programme//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, abstract = {BACKGROUND: Floral organs are specified by MADS-domain transcription factors that act in a combinatorial manner, as summarized in the (A)BCE model. However, this evolutionarily conserved model is in contrast to a remarkable amount of morphological diversity in flowers. One of the mechanisms suggested to contribute to this diversity is duplication of floral MADS-domain transcription factors. Although gene duplication is often followed by loss of one of the copies, sometimes both copies are retained. If both copies are retained they will initially be redundant, providing freedom for one of the paralogs to change function. Here, we examine the evolutionary fate and functional consequences of a transposition event at the base of the Brassicales that resulted in the duplication of the floral regulator PISTILLATA (PI), using Tarenaya hassleriana (Cleomaceae) as a model system.

RESULTS: The transposition of a genomic region containing a PI gene led to two paralogs which are located at different positions in the genome. The original PI copy is syntenic in position with most angiosperms, whereas the transposed copy is syntenic with the PI genes in Brassicaceae. The two PI paralogs of T. hassleriana have very similar expression patterns. However, they may have diverged in function, as only one of these PI proteins was able to act heterologously in the first whorl of A. thaliana flowers. We also observed differences in protein complex formation between the two paralogs, and the two paralogs exhibit subtle differences in DNA-binding specificity. Sequence analysis indicates that most of the protein sequence divergence between the two T. hassleriana paralogs emerged in a common ancestor of the Cleomaceae and the Brassicaceae.

CONCLUSIONS: We found that the PI paralogs in T. hassleriana have similar expression patterns, but may have diverged at the level of protein function. Data suggest that most protein sequence divergence occurred rapidly, prior to the origin of the Brassicaceae and Cleomaceae. It is tempting to speculate that the interaction specificities of the Brassicaceae-specific PI proteins are different compared to the PI found in other angiosperms. This could lead to PI regulating partly different genes in the Brassicaceae, and ultimately might result in change floral in morphology.}, } @article {pmid30577803, year = {2018}, author = {Chappell, T and Geva, S and Hogan, JM and Huygens, F and Rathnayake, IU and Rudd, S and Kelly, W and Perrin, D}, title = {Rapid analysis of metagenomic data using signature-based clustering.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {509}, doi = {10.1186/s12859-018-2540-4}, pmid = {30577803}, issn = {1471-2105}, mesh = {Algorithms ; Cluster Analysis ; *Data Analysis ; Humans ; Metagenomics/*methods ; Microbiota/genetics ; }, abstract = {BACKGROUND: Sequencing highly-variable 16S regions is a common and often effective approach to the study of microbial communities, and next-generation sequencing (NGS) technologies provide abundant quantities of data for analysis. However, the speed of existing analysis pipelines may limit our ability to work with these quantities of data. Furthermore, the limited coverage of existing 16S databases may hamper our ability to characterise these communities, particularly in the context of complex or poorly studied environments.

RESULTS: In this article we present the SigClust algorithm, a novel clustering method involving the transformation of sequence reads into binary signatures. When compared to other published methods, SigClust yields superior cluster coherence and separation of metagenomic read data, while operating within substantially reduced timeframes. We demonstrate its utility on published Illumina datasets and on a large collection of labelled wound reads sourced from patients in a wound clinic. The temporal analysis is based on tracking the dominant clusters of wound samples over time. The analysis can identify markers of both healing and non-healing wounds in response to treatment. Prominent clusters are found, corresponding to bacterial species known to be associated with unfavourable healing outcomes, including a number of strains of Staphylococcus aureus.

CONCLUSIONS: SigClust identifies clusters rapidly and supports an improved understanding of the wound microbiome without reliance on a reference database. The results indicate a promising use for a SigClust-based pipeline in wound analysis and prediction, and a possible novel method for wound management and treatment.}, } @article {pmid30577795, year = {2018}, author = {Matelska, D and Shabalin, IG and Jabłońska, J and Domagalski, MJ and Kutner, J and Ginalski, K and Minor, W}, title = {Classification, substrate specificity and structural features of D-2-hydroxyacid dehydrogenases: 2HADH knowledgebase.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {199}, doi = {10.1186/s12862-018-1309-8}, pmid = {30577795}, issn = {1471-2148}, support = {HHSN272201200026C//National Institute of Allergy and Infectious Diseases/International ; HHSN272201700060C//National Institute of Allergy and Infectious Diseases/International ; HG008424/NH/NIH HHS/United States ; GM094662/NH/NIH HHS/United States ; GM118619/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: The family of D-isomer specific 2-hydroxyacid dehydrogenases (2HADHs) contains a wide range of oxidoreductases with various metabolic roles as well as biotechnological applications. Despite a vast amount of biochemical and structural data for various representatives of the family, the long and complex evolution and broad sequence diversity hinder functional annotations for uncharacterized members.

RESULTS: We report an in-depth phylogenetic analysis, followed by mapping of available biochemical and structural data on the reconstructed phylogenetic tree. The analysis suggests that some subfamilies comprising enzymes with similar yet broad substrate specificity profiles diverged early in the evolution of 2HADHs. Based on the phylogenetic tree, we present a revised classification of the family that comprises 22 subfamilies, including 13 new subfamilies not studied biochemically. We summarize characteristics of the nine biochemically studied subfamilies by aggregating all available sequence, biochemical, and structural data, providing comprehensive descriptions of the active site, cofactor-binding residues, and potential roles of specific structural regions in substrate recognition. In addition, we concisely present our analysis as an online 2HADH enzymes knowledgebase.

CONCLUSIONS: The knowledgebase enables navigation over the 2HADHs classification, search through collected data, and functional predictions of uncharacterized 2HADHs. Future characterization of the new subfamilies may result in discoveries of enzymes with novel metabolic roles and with properties beneficial for biotechnological applications.}, } @article {pmid30577794, year = {2018}, author = {Wang, YB and You, ZH and Li, X and Jiang, TH and Cheng, L and Chen, ZH}, title = {Prediction of protein self-interactions using stacked long short-term memory from protein sequences information.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {129}, doi = {10.1186/s12918-018-0647-x}, pmid = {30577794}, issn = {1752-0509}, abstract = {BACKGROUND: Self-interacting Proteins (SIPs) plays a critical role in a series of life function in most living cells. Researches on SIPs are important part of molecular biology. Although numerous SIPs data be provided, traditional experimental methods are labor-intensive, time-consuming and costly and can only yield limited results in real-world needs. Hence,it's urgent to develop an efficient computational SIPs prediction method to fill the gap. Deep learning technologies have proven to produce subversive performance improvements in many areas, but the effectiveness of deep learning methods for SIPs prediction has not been verified.

RESULTS: We developed a deep learning model for predicting SIPs by constructing a Stacked Long Short-Term Memory (SLSTM) neural network that contains "dropout". We extracted features from protein sequences using a novel feature extraction scheme that combined Zernike Moments (ZMs) with Position Specific Weight Matrix (PSWM). The capability of the proposed approach was assessed on S.erevisiae and Human SIPs datasets. The result indicates that the approach based on deep learning can effectively resist data skew and achieve good accuracies of 95.69 and 97.88%, respectively. To demonstrate the progressiveness of deep learning, we compared the results of the SLSTM-based method and the celebrated Support Vector Machine (SVM) method and several other well-known methods on the same datasets.

CONCLUSION: The results show that our method is overall superior to any of the other existing state-of-the-art techniques. As far as we know, this study first applies deep learning method to predict SIPs, and practical experimental results reveal its potential in SIPs identification.}, } @article {pmid30577793, year = {2018}, author = {Ren, J and Wang, B and Li, J}, title = {Integrating proteomic and phosphoproteomic data for pathway analysis in breast cancer.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {130}, doi = {10.1186/s12918-018-0646-y}, pmid = {30577793}, issn = {1752-0509}, abstract = {BACKGROUND: As protein is the basic unit of cell function and biological pathway, shotgun proteomics, the large-scale analysis of proteins, is contributing greatly to our understanding of disease mechanisms. Proteomics study could detect the changes of both protein expression and modification. With the releases of large-scale cancer proteome studies, how to integrate acquired proteomic and phosphoproteomic data in more comprehensive pathway analysis becomes implemented, but remains challenging. Integrative pathway analysis at proteome level provides a systematic insight into the signaling network adaptations in the development of cancer.

RESULTS: Here we integrated proteomic and phosphoproteomic data to perform pathway prioritization in breast cancer. We manually collected and curated breast cancer well-known related pathways from the literature as target pathways (TPs) or positive control in method evaluation. Three different strategies including Hypergeometric test based over-representation analysis, Kolmogorov-Smirnov (K-S) test based gene set analysis and topology-based pathway analysis, were applied and evaluated in integrating protein expression and phosphorylation. In comparison, we also assessed the ranking performance of the strategy using information of protein expression or protein phosphorylation individually. Target pathways were ranked more top with the data integration than using the information from proteomic or phosphoproteomic data individually. In the comparisons of pathway analysis strategies, topology-based method outperformed than the others. The subtypes of breast cancer, which consist of Luminal A, Luminal B, Basal and HER2-enriched, vary greatly in prognosis and require distinct treatment. Therefore we applied topology-based pathway analysis with integrating protein expression and phosphorylation profiles on four subtypes of breast cancer. The results showed that TPs were enriched in all subtypes but their ranks were significantly different among the subtypes. For instance, p53 pathway ranked top in the Basal-like breast cancer subtype, but not in HER2-enriched type. The rank of Focal adhesion pathway was more top in HER2- subtypes than in HER2+ subtypes. The results were consistent with some previous researches.

CONCLUSIONS: The results demonstrate that the network topology-based method is more powerful by integrating proteomic and phosphoproteomic in pathway analysis of proteomics study. This integrative strategy can also be used to rank the specific pathways for the disease subtypes.}, } @article {pmid30577788, year = {2018}, author = {Picart-Armada, S and Fernández-Albert, F and Vinaixa, M and Yanes, O and Perera-Lluna, A}, title = {FELLA: an R package to enrich metabolomics data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {538}, doi = {10.1186/s12859-018-2487-5}, pmid = {30577788}, issn = {1471-2105}, support = {TEC2014-60337-R//Ministerio de Economía y Competitividad/ ; DPI2017-89827-R//Ministerio de Economía y Competitividad/ ; BFU2014-57466-P//Ministerio de Economía y Competitividad/ ; }, mesh = {Animals ; Computational Biology/*methods ; Computer Graphics ; Datasets as Topic ; Female ; Humans ; Malaria/metabolism/pathology ; *Metabolic Networks and Pathways ; Metabolomics/*methods ; Mice ; Models, Biological ; Non-alcoholic Fatty Liver Disease/metabolism/pathology ; Ovarian Neoplasms/metabolism/pathology ; *Software ; Zebrafish ; }, abstract = {BACKGROUND: Pathway enrichment techniques are useful for understanding experimental metabolomics data. Their purpose is to give context to the affected metabolites in terms of the prior knowledge contained in metabolic pathways. However, the interpretation of a prioritized pathway list is still challenging, as pathways show overlap and cross talk effects.

RESULTS: We introduce FELLA, an R package to perform a network-based enrichment of a list of affected metabolites. FELLA builds a hierarchical representation of an organism biochemistry from the Kyoto Encyclopedia of Genes and Genomes (KEGG), containing pathways, modules, enzymes, reactions and metabolites. In addition to providing a list of pathways, FELLA reports intermediate entities (modules, enzymes, reactions) that link the input metabolites to them. This sheds light on pathway cross talk and potential enzymes or metabolites as targets for the condition under study. FELLA has been applied to six public datasets -three from Homo sapiens, two from Danio rerio and one from Mus musculus- and has reproduced findings from the original studies and from independent literature.

CONCLUSIONS: The R package FELLA offers an innovative enrichment concept starting from a list of metabolites, based on a knowledge graph representation of the KEGG database that focuses on interpretability. Besides reporting a list of pathways, FELLA suggests intermediate entities that are of interest per se. Its usefulness has been shown at several molecular levels on six public datasets, including human and animal models. The user can run the enrichment analysis through a simple interactive graphical interface or programmatically. FELLA is publicly available in Bioconductor under the GPL-3 license.}, } @article {pmid30577783, year = {2018}, author = {San Lucas, FA and Redell, J and Pramod, D and Liu, Y}, title = {Classifying mild traumatic brain injuries with functional network analysis.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {131}, doi = {10.1186/s12918-018-0645-z}, pmid = {30577783}, issn = {1752-0509}, support = {R01 CA163481/CA/NCI NIH HHS/United States ; R01 LM010022/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Traumatic brain injury (TBI) represents a critical health problem of which timely diagnosis and treatment remain challenging. TBI is a result of an external force damaging brain tissue, accompanied by delayed pathogenic events which aggravate the injury. Molecular responses to different mild TBI subtypes have not been well characterized. TBI subtype classification is an important step towards the development and application of novel treatments. The computational systems biology approach is proved to be a promising tool in biomarker discovery for central nervous system injury.

RESULTS: In this study, we have performed a network-based analysis on gene expression profiles to identify functional gene subnetworks. The gene expression profiles were obtained from two experimental models of injury in rats: the controlled cortical impact and the fluid percussion injury. Our method integrates protein interaction information with gene expression profiles to identify subnetworks of genes as biomarkers. We have demonstrated that the selected gene subnetworks are more accurate to classify the heterogeneous responses to different injury models, compared to conventional analysis using individual marker genes selected without network information.

CONCLUSIONS: The systems approach can lead to a better understanding of the underlying complexities of the molecular responses after TBI and the identified subnetworks will have important prognostic functions for patients who sustain mild TBIs.}, } @article {pmid30577777, year = {2018}, author = {Bhowmik, D and Gao, S and Young, MT and Ramanathan, A}, title = {Deep clustering of protein folding simulations.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {484}, doi = {10.1186/s12859-018-2507-5}, pmid = {30577777}, issn = {1471-2105}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Cluster Analysis ; Molecular Dynamics Simulation ; *Protein Folding ; }, abstract = {BACKGROUND: We examine the problem of clustering biomolecular simulations using deep learning techniques. Since biomolecular simulation datasets are inherently high dimensional, it is often necessary to build low dimensional representations that can be used to extract quantitative insights into the atomistic mechanisms that underlie complex biological processes.

RESULTS: We use a convolutional variational autoencoder (CVAE) to learn low dimensional, biophysically relevant latent features from long time-scale protein folding simulations in an unsupervised manner. We demonstrate our approach on three model protein folding systems, namely Fs-peptide (14 μs aggregate sampling), villin head piece (single trajectory of 125 μs) and β- β- α (BBA) protein (223 + 102 μs sampling across two independent trajectories). In these systems, we show that the CVAE latent features learned correspond to distinct conformational substates along the protein folding pathways. The CVAE model predicts, on average, nearly 89% of all contacts within the folding trajectories correctly, while being able to extract folded, unfolded and potentially misfolded states in an unsupervised manner. Further, the CVAE model can be used to learn latent features of protein folding that can be applied to other independent trajectories, making it particularly attractive for identifying intrinsic features that correspond to conformational substates that share similar structural features.

CONCLUSIONS: Together, we show that the CVAE model can quantitatively describe complex biophysical processes such as protein folding.}, } @article {pmid30577771, year = {2018}, author = {Chen, X and Qi, S and Zhang, D and Li, Y and An, N and Zhao, C and Zhao, J and Shah, K and Han, M and Xing, L}, title = {Comparative RNA-sequencing-based transcriptome profiling of buds from profusely flowering 'Qinguan' and weakly flowering 'Nagafu no. 2' apple varieties reveals novel insights into the regulatory mechanisms underlying floral induction.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {370}, doi = {10.1186/s12870-018-1555-3}, pmid = {30577771}, issn = {1471-2229}, support = {the National Natural Science Foundation of China//the National Natural Science Foundation of China/ ; 31701664//the National Natural Science Foundation of China/ ; 2016KTZDNY01-10//Science and Technology Innovative Engineering Project in the Shaanxi province of China/ ; 2017ZDXM-NY-017//Science and Technology Innovative Engineering Project in the Shaanxi province of China/ ; 2018M631207//China Postdoctoral Science Foundation/ ; 2017M623254//China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: Floral induction is an important stage in the apple tree life cycle. In 'Nagafu No. 2', which was derived from a 'Fuji' bud sport, flower bud formation is associated with serious problems, such as fewer and inferior flower buds, a long juvenile phase, and an alternate bearing phenotype. Moreover, the molecular regulatory mechanisms underlying apple floral induction remain unknown. To characterize these mechanisms, we compared the RNA-sequencing-based transcriptome profiles of buds during floral induction in profusely flowering 'Qinguan' and weakly flowering 'Nagafu No. 2' apple varieties.

RESULTS: Genes differentially expressed between the buds of the two varieties were mainly related to carbohydrate, fatty acid, and lipid pathways. Additionally, the steady up-regulated expression of genes related to the fatty acid and lipid pathways and the down-regulated expression of starch synthesis-related genes in the carbon metabolic pathway of 'Qinguan' relative to 'Nagafu No. 2' were observed to contribute to the higher flowering rate of 'Qinguan'. Additionally, global gene expression profiling revealed that genes related to cytokinin, indole-3-acetic acid, and gibberellin synthesis, signalling, and responses (i.e., factors contributing to cell division and differentiation and bud growth) were significantly differentially expressed between the two varieties. The up-regulated expression of genes involved in abscisic acid and salicylic acid biosynthesis via shikimate pathways as well as jasmonic acid production through fatty acid pathways in 'Qinguan' buds were also revealed to contribute to the floral induction and relatively high flowering rate of this variety. The differential expression of transcription factor genes (i.e., SPL, bZIP, IDD, and MYB genes) involved in multiple biological processes was also observed to play key roles in floral induction. Finally, important flowering genes (i.e., FT, FD, and AFL) were significantly more highly expressed in 'Qinguan' buds than in 'Nagafu No. 2' buds during floral induction.

CONCLUSIONS: A complex genetic network of regulatory mechanisms involving carbohydrate, fatty acid, lipid, and hormone pathways may mediate the induction of apple tree flowering.}, } @article {pmid30577765, year = {2018}, author = {Srivastava, M and James, A and Varma, V and Sharma, VK and Sheeba, V}, title = {Environmental cycles regulate development time via circadian clock mediated gating of adult emergence.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {21}, doi = {10.1186/s12861-018-0180-6}, pmid = {30577765}, issn = {1471-213X}, abstract = {BACKGROUND: Previous studies have implicated a role for circadian clocks in regulating pre-adult development of organisms. Among them two approaches are most notable: 1) use of insects whose clocks have different free-running periods and 2) imposition of artificial selection on either rate of development, timing of emergence or circadian period in laboratory populations. Using these two approaches, influence of clock on rate of development has been elucidated. However, the contribution of circadian clocks in determining time taken for pre-adult development has remained unclear. Here we present results of our studies aimed to understand this influence by examining populations of fruit flies carrying three different alleles of the period gene and hence having different free-running periods. We tried to achieve similarity of genetic background among the three strains while also ensuring that they harbored sufficient variation on loci other than period gene.

RESULTS: We find that under constant conditions, flies with long period have slower development whereas in presence of light-dark cycles (LD) of various lengths, the speed of development for each genotype is influenced by whether their eclosion rhythms can entrain to them. Under LD 12:12 (T24), where all three strains entrain, they do not show any difference in time taken for emergence, whereas under LD 10:10 (T20) where long period flies do not entrain and LD 14:14 (T28) where short period flies do not entrain, they have slower and faster pre-adult development, respectively, compared to the controls. We also show that a prior stage in development namely pupation is not rhythmic though time taken for pupation is determined by both the environmental cycle and period allele.

CONCLUSION: We discuss how in presence of daily time cues, interaction of the cyclic environmental factors with the clock determines the position and width of the gate available for a fly to emerge (duration of time within a cycle when adult emergence can occur) resulting in an altered developmental duration from that observed under constant conditions. We also discuss the relevance of genetic background influencing this regulation.}, } @article {pmid30577761, year = {2018}, author = {Rush, STA and Repsilber, D}, title = {Capturing context-specific regulation in molecular interaction networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {539}, doi = {10.1186/s12859-018-2513-7}, pmid = {30577761}, issn = {1471-2105}, support = {20110225//Stiftelsen för Kunskaps- och Kompetensutveckling/ ; }, mesh = {Air Pollutants/*adverse effects ; *Algorithms ; Computational Biology/*methods ; *Gene Expression Profiling ; *Gene Regulatory Networks ; Humans ; Pneumonia/etiology/*genetics/pathology ; *Software ; }, abstract = {BACKGROUND: Molecular profiles change in response to perturbations. These changes are coordinated into functional modules via regulatory interactions. The genes and their products within a functional module are expected to be differentially expressed in a manner coherent with their regulatory network. This perspective presents a promising approach to increase precision in detecting differential signals as well as for describing differential regulatory signals within the framework of a priori knowledge about the underlying network, and so from a mechanistic point of view.

RESULTS: We present Coherent Network Expression (CoNE), an effective procedure for identifying differentially activated functional modules in molecular interaction networks. Differential gene expression is chosen as example, and differential signals coherent with the regulatory nature of the network are identified. We apply our procedure to systematically simulated data, comparing its performance to alternative methods. We then take the example case of a transcription regulatory network in the context of particle-induced pulmonary inflammation, recapitulating and proposing additional candidates to previously obtained results. CoNE is conveniently implemented in an R-package along with simulation utilities.

CONCLUSION: Combining coherent interactions with error control on differential gene expression results in uniformly greater specificity in inference than error control alone, ensuring that captured functional modules constitute real findings.}, } @article {pmid30577759, year = {2018}, author = {Tang, G and Shi, J and Wu, W and Yue, X and Zhang, W}, title = {Sequence-based bacterial small RNAs prediction using ensemble learning strategies.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {503}, doi = {10.1186/s12859-018-2535-1}, pmid = {30577759}, issn = {1471-2105}, mesh = {*Algorithms ; Area Under Curve ; Bacteria/*genetics ; Base Sequence ; Benchmarking ; Computational Biology/*methods ; Databases, Nucleic Acid ; Neural Networks (Computer) ; RNA, Bacterial/*genetics ; RNA, Untranslated/*genetics ; }, abstract = {BACKGROUND: Bacterial small non-coding RNAs (sRNAs) have emerged as important elements in diverse physiological processes, including growth, development, cell proliferation, differentiation, metabolic reactions and carbon metabolism, and attract great attention. Accurate prediction of sRNAs is important and challenging, and helps to explore functions and mechanism of sRNAs.

RESULTS: In this paper, we utilize a variety of sRNA sequence-derived features to develop ensemble learning methods for the sRNA prediction. First, we compile a balanced dataset and four imbalanced datasets. Then, we investigate various sRNA sequence-derived features, such as spectrum profile, mismatch profile, reverse compliment k-mer and pseudo nucleotide composition. Finally, we consider two ensemble learning strategies to integrate all features for building ensemble learning models for the sRNA prediction. One is the weighted average ensemble method (WAEM), which uses the linear weighted sum of outputs from the individual feature-based predictors to predict sRNAs. The other is the neural network ensemble method (NNEM), which trains a deep neural network by combining diverse features. In the computational experiments, we evaluate our methods on these five datasets by using 5-fold cross validation. WAEM and NNEM can produce better results than existing state-of-the-art sRNA prediction methods.

CONCLUSIONS: WAEM and NNEM have great potential for the sRNA prediction, and are helpful for understanding the biological mechanism of bacteria.}, } @article {pmid30577756, year = {2018}, author = {Hengartner, N and Cuellar, L and Wu, XC and Tourassi, G and Qiu, J and Christian, B and Bhattacharya, T}, title = {CAT: computer aided triage improving upon the Bayes risk through ε-refusal triage rules.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {485}, doi = {10.1186/s12859-018-2503-9}, pmid = {30577756}, issn = {1471-2105}, mesh = {Bayes Theorem ; Computers/*trends ; Databases, Factual/*trends ; Humans ; Information Storage and Retrieval ; Triage/*methods ; }, abstract = {BACKGROUND: Manual extraction of information from electronic pathology (epath) reports to populate the Surveillance, Epidemiology, and End Result (SEER) database is labor intensive. Systematizing the data extraction automatically using machine-learning (ML) and natural language processing (NLP) is desirable to reduce the human labor required to populate the SEER database and to improve the timeliness of the data. This enables scaling up registry efficiency and collection of new data elements. To ensure the integrity, quality, and continuity of the SEER data, the misclassification error of ML and NPL algorithms needs to be negligible. Current algorithms fail to achieve the precision of human experts who can bring additional information in their assessments. Differences in registry format and the desire to develop a common information extraction platform further complicate the ML/NLP tasks. The purpose of our study is to develop triage rules to partially automate registry workflow to improve the precision of the auto-extracted information.

RESULTS: This paper presents a mathematical framework to improve the precision of a classifier beyond that of the Bayes classifier by selectively classifying item that are most likely to be correct. This results in a triage rule that only classifies a subset of the item. We characterize the optimal triage rule and demonstrate its usefulness in the problem of classifying cancer site from electronic pathology reports to achieve a desired precision.

CONCLUSIONS: From the mathematical formalism, we propose a heuristic estimate for triage rule based on post-processing the soft-max output from standard machine learning algorithms. We show, in test cases, that the triage rule significantly improve the classification accuracy.}, } @article {pmid30577754, year = {2018}, author = {Xia, F and Shukla, M and Brettin, T and Garcia-Cardona, C and Cohn, J and Allen, JE and Maslov, S and Holbeck, SL and Doroshow, JH and Evrard, YA and Stahlberg, EA and Stevens, RL}, title = {Predicting tumor cell line response to drug pairs with deep learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {486}, doi = {10.1186/s12859-018-2509-3}, pmid = {30577754}, issn = {1471-2105}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; Deep Learning/*trends ; Drug Evaluation, Preclinical/*methods ; Humans ; National Cancer Institute (U.S.) ; Neural Networks (Computer) ; United States ; }, abstract = {BACKGROUND: The National Cancer Institute drug pair screening effort against 60 well-characterized human tumor cell lines (NCI-60) presents an unprecedented resource for modeling combinational drug activity.

RESULTS: We present a computational model for predicting cell line response to a subset of drug pairs in the NCI-ALMANAC database. Based on residual neural networks for encoding features as well as predicting tumor growth, our model explains 94% of the response variance. While our best result is achieved with a combination of molecular feature types (gene expression, microRNA and proteome), we show that most of the predictive power comes from drug descriptors. To further demonstrate value in detecting anticancer therapy, we rank the drug pairs for each cell line based on model predicted combination effect and recover 80% of the top pairs with enhanced activity.

CONCLUSIONS: We present promising results in applying deep learning to predicting combinational drug response. Our feature analysis indicates screening data involving more cell lines are needed for the models to make better use of molecular features.}, } @article {pmid30577753, year = {2018}, author = {Dakka, J and Turilli, M and Wright, DW and Zasada, SJ and Balasubramanian, V and Wan, S and Coveney, PV and Jha, S}, title = {High-throughput binding affinity calculations at extreme scales.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {482}, doi = {10.1186/s12859-018-2506-6}, pmid = {30577753}, issn = {1471-2105}, mesh = {High-Throughput Screening Assays/*methods ; Humans ; Protein Binding/*physiology ; }, abstract = {BACKGROUND: Resistance to chemotherapy and molecularly targeted therapies is a major factor in limiting the effectiveness of cancer treatment. In many cases, resistance can be linked to genetic changes in target proteins, either pre-existing or evolutionarily selected during treatment. Key to overcoming this challenge is an understanding of the molecular determinants of drug binding. Using multi-stage pipelines of molecular simulations we can gain insights into the binding free energy and the residence time of a ligand, which can inform both stratified and personal treatment regimes and drug development. To support the scalable, adaptive and automated calculation of the binding free energy on high-performance computing resources, we introduce the High-throughput Binding Affinity Calculator (HTBAC). HTBAC uses a building block approach in order to attain both workflow flexibility and performance.

RESULTS: We demonstrate close to perfect weak scaling to hundreds of concurrent multi-stage binding affinity calculation pipelines. This permits a rapid time-to-solution that is essentially invariant of the calculation protocol, size of candidate ligands and number of ensemble simulations.

CONCLUSIONS: As such, HTBAC advances the state of the art of binding affinity calculations and protocols. HTBAC provides the platform to enable scientists to study a wide range of cancer drugs and candidate ligands in order to support personalized clinical decision making based on genome sequencing and drug discovery.}, } @article {pmid30577752, year = {2018}, author = {Vadell, E and Cavender, JC and Landolt, JC and Perrigo, AL and Liu, P and Stephenson, SL}, title = {Five new species of dictyostelid social amoebae (Amoebozoa) from Thailand.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {198}, doi = {10.1186/s12862-018-1328-5}, pmid = {30577752}, issn = {1471-2148}, abstract = {BACKGROUND: Dictyostelid cellular slime molds (dictyostelids) are common inhabitants of the soil and leaf litter layer of fields and forests, along with animal dung, where they feed mostly on bacteria. However, reports on the species diversity of dictyostelids in South Asia, particularly Thailand, are limited. The research reported in this paper was carried out to increase our knowledge of the species diversity of this group of organisms in northern Thailand.

RESULTS: Forty soil samples were collected at four localities in northern Thailand to assess the species richness of dictyostelids. These samples yielded five dictyostelid isolates that were not morphologically consistent with any described species. Based on molecular signatures, all five of these isolates were assigned to the family Cavenderiaceae, genus Cavenderia. All five share a number of morphological similarities with other known species from this family. The new taxa differ from previously described species primarily in the size and complexity of their fruiting bodies (sorocarps). This paper describes these new species (Cavenderia aureostabilis, C. bhumiboliana, C. protodigitata, C. pseudoaureostipes, and C. subdiscoidea) based on a combination of morphological characteristics and their phylogenetic positions.

CONCLUSIONS: At least 15 taxa of dictyostelids were obtained from the four localities in northern Thailand, which indicates the high level of species diversity in this region. Five species were found to be new to science. These belong to the family Cavenderiaceae, genus Cavenderia, and were described based on both morphology and phylogeny.}, } @article {pmid30577751, year = {2018}, author = {Sanaullah, A and Yang, C and Alexeev, Y and Yoshii, K and Herbordt, MC}, title = {Real-time data analysis for medical diagnosis using FPGA-accelerated neural networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {490}, doi = {10.1186/s12859-018-2505-7}, pmid = {30577751}, issn = {1471-2105}, mesh = {Data Analysis ; Humans ; Machine Learning/*trends ; Neoplasms/*diagnosis/pathology ; *Neural Networks (Computer) ; }, abstract = {BACKGROUND: Real-time analysis of patient data during medical procedures can provide vital diagnostic feedback that significantly improves chances of success. With sensors becoming increasingly fast, frameworks such as Deep Neural Networks are required to perform calculations within the strict timing constraints for real-time operation. However, traditional computing platforms responsible for running these algorithms incur a large overhead due to communication protocols, memory accesses, and static (often generic) architectures. In this work, we implement a low-latency Multi-Layer Perceptron (MLP) processor using Field Programmable Gate Arrays (FPGAs). Unlike CPUs and Graphics Processing Units (GPUs), our FPGA-based design can directly interface sensors, storage devices, display devices and even actuators, thus reducing the delays of data movement between ports and compute pipelines. Moreover, the compute pipelines themselves are tailored specifically to the application, improving resource utilization and reducing idle cycles. We demonstrate the effectiveness of our approach using mass-spectrometry data sets for real-time cancer detection.

RESULTS: We demonstrate that correct parameter sizing, based on the application, can reduce latency by 20% on average. Furthermore, we show that in an application with tightly coupled data-path and latency constraints, having a large amount of computing resources can actually reduce performance. Using mass-spectrometry benchmarks, we show that our proposed FPGA design outperforms both CPU and GPU implementations, with an average speedup of 144x and 21x, respectively.

CONCLUSION: In our work, we demonstrate the importance of application-specific optimizations in order to minimize latency and maximize resource utilization for MLP inference. By directly interfacing and processing sensor data with ultra-low latency, FPGAs can perform real-time analysis during procedures and provide diagnostic feedback that can be critical to achieving higher percentages of successful patient outcomes.}, } @article {pmid30577750, year = {2018}, author = {Xu, J and Liu, S and Yin, P and Bulun, S and Dai, Y}, title = {MeDEStrand: an improved method to infer genome-wide absolute methylation levels from DNA enrichment data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {540}, doi = {10.1186/s12859-018-2574-7}, pmid = {30577750}, issn = {1471-2105}, support = {P01-HD057877//National Institutes of Health/ ; P01-HD057877//National Institutes of Health/ ; }, mesh = {Cells, Cultured ; CpG Islands ; DNA/*analysis/metabolism ; *DNA Methylation ; *Epigenesis, Genetic ; Fibroblasts/cytology/*metabolism ; *Genome, Human ; Genomics/methods ; Humans ; Mammary Glands, Human/cytology/*metabolism ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: DNA methylation of CpG dinucleotides is an essential epigenetic modification that plays a key role in transcription. Widely used DNA enrichment-based methods offer high coverage for measuring methylated CpG dinucleotides, with the lowest cost per CpG covered genome-wide. However, these methods measure the DNA enrichment of methyl-CpG binding, and thus do not provide information on absolute methylation levels. Further, the enrichment is influenced by various confounding factors in addition to methylation status, for example, CpG density. Computational models that can accurately derive absolute methylation levels from DNA enrichment data are needed.

RESULTS: We developed "MeDEStrand," a method that uses a sigmoid function to estimate and correct the CpG bias from enrichment results to infer absolute DNA methylation levels. Unlike previous methods, which estimate CpG bias based on reads mapped at the same genomic loci, MeDEStrand processes the reads for the positive and negative DNA strands separately. We compared the performance of MeDEStrand to that of three other state-of-the-art methods "MEDIPS," "BayMeth," and "QSEA" on four independent datasets generated using immortalized cell lines (GM12878 and K562) and human primary cells (foreskin fibroblasts and mammary epithelial cells). Based on the comparison of the inferred absolute methylation levels from MeDIP-seq data and the corresponding reduced-representation bisulfite sequencing data from each method, MeDEStrand showed the best performance at high resolution of 25, 50, and 100 base pairs.

CONCLUSIONS: The MeDEStrand tool can be used to infer whole-genome absolute DNA methylation levels at the same cost of enrichment-based methods with adequate accuracy and resolution. R package MeDEStrand and its tutorial is freely available for download at https://github.com/jxu1234/MeDEStrand.git .}, } @article {pmid30577748, year = {2018}, author = {Fu, K and Chronis, C and Soufi, A and Bonora, G and Edwards, M and Smale, ST and Zaret, KS and Plath, K and Pellegrini, M}, title = {Comparison of reprogramming factor targets reveals both species-specific and conserved mechanisms in early iPSC reprogramming.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {956}, doi = {10.1186/s12864-018-5326-1}, pmid = {30577748}, issn = {1471-2164}, support = {5P01GM099134//National Institutes of Health/ ; }, abstract = {BACKGROUND: Both human and mouse fibroblasts can be reprogrammed to pluripotency with Oct4, Sox2, Klf4, and c-Myc (OSKM) transcription factors. While both systems generate pluripotency, human reprogramming takes considerably longer than mouse.

RESULTS: To assess additional similarities and differences, we sought to compare the binding of the reprogramming factors between the two systems. In human fibroblasts, the OSK factors initially target many more closed chromatin sites compared to mouse. Despite this difference, the intra- and intergenic distribution of target sites, target genes, primary binding motifs, and combinatorial binding patterns between the reprogramming factors are largely shared. However, while many OSKM binding events in early mouse cell reprogramming occur in syntenic regions, only a limited number is conserved in human.

CONCLUSIONS: Our findings suggest similar general effects of OSKM binding across these two species, even though the detailed regulatory networks have diverged significantly.}, } @article {pmid30577747, year = {2018}, author = {Agibetov, A and Blagec, K and Xu, H and Samwald, M}, title = {Fast and scalable neural embedding models for biomedical sentence classification.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {541}, doi = {10.1186/s12859-018-2496-4}, pmid = {30577747}, issn = {1471-2105}, support = {668353//Horizon 2020 ()/ ; }, mesh = {*Biomedical Research ; Humans ; Language ; *Natural Language Processing ; *Neural Networks (Computer) ; PubMed/*standards ; *Unified Medical Language System ; }, abstract = {BACKGROUND: Biomedical literature is expanding rapidly, and tools that help locate information of interest are needed. To this end, a multitude of different approaches for classifying sentences in biomedical publications according to their coarse semantic and rhetoric categories (e.g., Background, Methods, Results, Conclusions) have been devised, with recent state-of-the-art results reported for a complex deep learning model. Recent evidence showed that shallow and wide neural models such as fastText can provide results that are competitive or superior to complex deep learning models while requiring drastically lower training times and having better scalability. We analyze the efficacy of the fastText model in the classification of biomedical sentences in the PubMed 200k RCT benchmark, and introduce a simple pre-processing step that enables the application of fastText on sentence sequences. Furthermore, we explore the utility of two unsupervised pre-training approaches in scenarios where labeled training data are limited.

RESULTS: Our fastText-based methodology yields a state-of-the-art F1 score of.917 on the PubMed 200k benchmark when sentence ordering is taken into account, with a training time of only 73 s on standard hardware. Applying fastText on single sentences, without taking sentence ordering into account, yielded an F1 score of.852 (training time 13 s). Unsupervised pre-training of N-gram vectors greatly improved the results for small training set sizes, with an increase of F1 score of.21 to.74 when trained on only 1000 randomly picked sentences without taking sentence ordering into account.

CONCLUSIONS: Because of it's ease of use and performance, fastText should be among the first choices of tools when tackling biomedical text classification problems with large corpora. Unsupervised pre-training of N-gram vectors on domain-specific corpora also makes it possible to apply fastText when labeled training data are limited.}, } @article {pmid30577746, year = {2018}, author = {Fischer, W and Moudgalya, SS and Cohn, JD and Nguyen, NTT and Kenyon, GT}, title = {Sparse coding of pathology slides compared to transfer learning with deep neural networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {489}, doi = {10.1186/s12859-018-2504-8}, pmid = {30577746}, issn = {1471-2105}, mesh = {Deep Learning/*trends ; Humans ; Neoplasms/*pathology ; *Neural Networks (Computer) ; }, abstract = {BACKGROUND: Histopathology images of tumor biopsies present unique challenges for applying machine learning to the diagnosis and treatment of cancer. The pathology slides are high resolution, often exceeding 1GB, have non-uniform dimensions, and often contain multiple tissue slices of varying sizes surrounded by large empty regions. The locations of abnormal or cancerous cells, which may constitute a small portion of any given tissue sample, are not annotated. Cancer image datasets are also extremely imbalanced, with most slides being associated with relatively common cancers. Since deep representations trained on natural photographs are unlikely to be optimal for classifying pathology slide images, which have different spectral ranges and spatial structure, we here describe an approach for learning features and inferring representations of cancer pathology slides based on sparse coding.

RESULTS: We show that conventional transfer learning using a state-of-the-art deep learning architecture pre-trained on ImageNet (RESNET) and fine tuned for a binary tumor/no-tumor classification task achieved between 85% and 86% accuracy. However, when all layers up to the last convolutional layer in RESNET are replaced with a single feature map inferred via a sparse coding using a dictionary optimized for sparse reconstruction of unlabeled pathology slides, classification performance improves to over 93%, corresponding to a 54% error reduction.

CONCLUSIONS: We conclude that a feature dictionary optimized for biomedical imagery may in general support better classification performance than does conventional transfer learning using a dictionary pre-trained on natural images.}, } @article {pmid30577745, year = {2018}, author = {Du, Y and Pan, Y and Wang, C and Ji, J}, title = {Biomedical semantic indexing by deep neural network with multi-task learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {502}, doi = {10.1186/s12859-018-2534-2}, pmid = {30577745}, issn = {1471-2105}, mesh = {*Abstracting and Indexing as Topic ; Algorithms ; *Deep Learning ; Humans ; *Neural Networks (Computer) ; *Semantics ; }, abstract = {BACKGROUND: Biomedical semantic indexing is important for information retrieval and many other research fields in bioinformatics. It annotates biomedical citations with Medical Subject Headings. In face of unbalanced category distribution in the training data, sampling methods are difficult to apply for semantic indexing task.

RESULTS: In this paper, we present a novel deep serial multi-task learning model. The primary task treats the biomedical semantic indexing as a multi-label text classification issue that considers the relations of the labels. The auxiliary task is a regression task that predicts the MeSH number of the citation and provides hints for the network to make it converge faster. The experimental results on the BioASQ-Task5A open dataset show that our model outperforms the state-of-the-art solution "MTI", proposed by the US National Library of Medicine. Further, it not only achieves the highest precision among all the solutions in BioASQ-Task5A but also has faster convergence speed compared with some naive deep learning methods.

CONCLUSIONS: Rather than parallel in an ordinary multi-task structure, the tasks in our model are serial and tightly coupled. It can achieve satisfied performance without any handcrafted feature.}, } @article {pmid30577744, year = {2018}, author = {Stephens, Z and Wang, C and Iyer, RK and Kocher, JP}, title = {Detection and visualization of complex structural variants from long reads.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {508}, doi = {10.1186/s12859-018-2539-x}, pmid = {30577744}, issn = {1471-2105}, mesh = {Computer Simulation ; Gene Duplication ; Genome, Human ; *Genomic Structural Variation ; Humans ; Sequence Alignment ; Sequence Analysis, DNA/*methods ; Software ; }, abstract = {BACKGROUND: With applications in cancer, drug metabolism, and disease etiology, understanding structural variation in the human genome is critical in advancing the thrusts of individualized medicine. However, structural variants (SVs) remain challenging to detect with high sensitivity using short read sequencing technologies. This problem is exacerbated when considering complex SVs comprised of multiple overlapping or nested rearrangements. Longer reads, such as those from Pacific Biosciences platforms, often span multiple breakpoints of such events, and thus provide a way to unravel small-scale complexities in SVs with higher confidence.

RESULTS: We present CORGi (COmplex Rearrangement detection with Graph-search), a method for the detection and visualization of complex local genomic rearrangements. This method leverages the ability of long reads to span multiple breakpoints to untangle SVs that appear very complicated with respect to a reference genome. We validated our approach against both simulated long reads, and real data from two long read sequencing technologies. We demonstrate the ability of our method to identify breakpoints inserted in synthetic data with high accuracy, and the ability to detect and plot SVs from NA12878 germline, achieving 88.4% concordance between the two sets of sequence data. The patterns of complexity we find in many NA12878 SVs match known mechanisms associated with DNA replication and structural variant formation, and highlight the ability of our method to automatically label complex SVs with an intuitive combination of adjacent or overlapping reference transformations.

CONCLUSIONS: CORGi is a method for interrogating genomic regions suspected to contain local rearrangements using long reads. Using pairwise alignments and graph search CORGi produces labels and visualizations for local SVs of arbitrary complexity.}, } @article {pmid30577743, year = {2018}, author = {Qiu, JX and Yoon, HJ and Srivastava, K and Watson, TP and Blair Christian, J and Ramanathan, A and Wu, XC and Fearn, PA and Tourassi, GD}, title = {Scalable deep text comprehension for Cancer surveillance on high-performance computing.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {488}, doi = {10.1186/s12859-018-2511-9}, pmid = {30577743}, issn = {1471-2105}, mesh = {Comprehension ; *Computing Methodologies ; Deep Learning/*trends ; Humans ; Neoplasms/*diagnosis/pathology ; Neural Networks (Computer) ; }, abstract = {BACKGROUND: Deep Learning (DL) has advanced the state-of-the-art capabilities in bioinformatics applications which has resulted in trends of increasingly sophisticated and computationally demanding models trained by larger and larger data sets. This vastly increased computational demand challenges the feasibility of conducting cutting-edge research. One solution is to distribute the vast computational workload across multiple computing cluster nodes with data parallelism algorithms. In this study, we used a High-Performance Computing environment and implemented the Downpour Stochastic Gradient Descent algorithm for data parallelism to train a Convolutional Neural Network (CNN) for the natural language processing task of information extraction from a massive dataset of cancer pathology reports. We evaluated the scalability improvements using data parallelism training and the Titan supercomputer at Oak Ridge Leadership Computing Facility. To evaluate scalability, we used different numbers of worker nodes and performed a set of experiments comparing the effects of different training batch sizes and optimizer functions.

RESULTS: We found that Adadelta would consistently converge at a lower validation loss, though requiring over twice as many training epochs as the fastest converging optimizer, RMSProp. The Adam optimizer consistently achieved a close 2nd place minimum validation loss significantly faster; using a batch size of 16 and 32 allowed the network to converge in only 4.5 training epochs.

CONCLUSIONS: We demonstrated that the networked training process is scalable across multiple compute nodes communicating with message passing interface while achieving higher classification accuracy compared to a traditional machine learning algorithm.}, } @article {pmid30577742, year = {2018}, author = {Ozik, J and Collier, N and Wozniak, JM and Macal, C and Cockrell, C and Friedman, SH and Ghaffarizadeh, A and Heiland, R and An, G and Macklin, P}, title = {High-throughput cancer hypothesis testing with an integrated PhysiCell-EMEWS workflow.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {483}, doi = {10.1186/s12859-018-2510-x}, pmid = {30577742}, issn = {1471-2105}, support = {R01 CA180149/CA/NCI NIH HHS/United States ; R01 GM115839/GM/NIGMS NIH HHS/United States ; S10 OD018495/OD/NIH HHS/United States ; }, mesh = {Humans ; Models, Theoretical ; Neoplasms/*diagnosis ; Workflow ; }, abstract = {BACKGROUND: Cancer is a complex, multiscale dynamical system, with interactions between tumor cells and non-cancerous host systems. Therapies act on this combined cancer-host system, sometimes with unexpected results. Systematic investigation of mechanistic computational models can augment traditional laboratory and clinical studies, helping identify the factors driving a treatment's success or failure. However, given the uncertainties regarding the underlying biology, these multiscale computational models can take many potential forms, in addition to encompassing high-dimensional parameter spaces. Therefore, the exploration of these models is computationally challenging. We propose that integrating two existing technologies-one to aid the construction of multiscale agent-based models, the other developed to enhance model exploration and optimization-can provide a computational means for high-throughput hypothesis testing, and eventually, optimization.

RESULTS: In this paper, we introduce a high throughput computing (HTC) framework that integrates a mechanistic 3-D multicellular simulator (PhysiCell) with an extreme-scale model exploration platform (EMEWS) to investigate high-dimensional parameter spaces. We show early results in applying PhysiCell-EMEWS to 3-D cancer immunotherapy and show insights on therapeutic failure. We describe a generalized PhysiCell-EMEWS workflow for high-throughput cancer hypothesis testing, where hundreds or thousands of mechanistic simulations are compared against data-driven error metrics to perform hypothesis optimization.

CONCLUSIONS: While key notational and computational challenges remain, mechanistic agent-based models and high-throughput model exploration environments can be combined to systematically and rapidly explore key problems in cancer. These high-throughput computational experiments can improve our understanding of the underlying biology, drive future experiments, and ultimately inform clinical practice.}, } @article {pmid30577741, year = {2018}, author = {Tran, N and Abhyankar, V and Nguyen, K and Weidanz, J and Gao, J}, title = {MicroRNA dysregulational synergistic network: discovering microRNA dysregulatory modules across subtypes in non-small cell lung cancers.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {504}, doi = {10.1186/s12859-018-2536-0}, pmid = {30577741}, issn = {1471-2105}, mesh = {Adenocarcinoma of Lung/genetics/pathology ; Biomarkers, Tumor/genetics ; Carcinoma, Non-Small-Cell Lung/*genetics/pathology ; Carcinoma, Squamous Cell/genetics/pathology ; Cohort Studies ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; Lung Neoplasms/*genetics/pathology ; MicroRNAs/*genetics/metabolism ; Neoplasm Staging ; ROC Curve ; Sample Size ; }, abstract = {BACKGROUND: The majority of cancer-related deaths are due to lung cancer, and there is a need for reliable diagnostic biomarkers to predict stages in non-small cell lung cancer cases. Recently, microRNAs were found to have potential as both biomarkers and therapeutic targets for lung cancer. However, some of the microRNA's functions are unknown, and their roles in cancer stage progression have been mostly undiscovered in this clinically and genetically heterogeneous disease. As evidence suggests that microRNA dysregulations are implicated in many diseases, it is essential to consider the changes in microRNA-target regulation across different lung cancer subtypes.

RESULTS: We proposed a pipeline to identify microRNA synergistic modules with similar dysregulation patterns across multiple subtypes by constructing the MicroRNA Dysregulational Synergistic Network. From the network, we extracted microRNA modules and incorporated them as prior knowledge to the Sparse Group Lasso classifier. This leads to a more relevant selection of microRNA biomarkers, thereby improving the cancer stage classification accuracy. We applied our method to the TCGA Lung Adenocarcinoma and the Lung Squamous Cell Carcinoma datasets. In cross-validation tests, the area under ROC curve rate for the cancer stages prediction has increased considerably when incorporating the learned microRNA dysregulation modules. The extracted modules from multiple independent subtypes differential analyses were found to have high agreement with microRNA family annotations, and they can also be used to identify mutual biomarkers between different subtypes. Among the top-ranked candidate microRNAs selected by the model, 87% were reported to be related to Lung Adenocarcinoma. The overall result demonstrates that clustering microRNAs from the dysregulation pattern between microRNAs and their targets leads to biomarkers with high precision and recall rate to known differentially expressed disease-associated microRNAs.

CONCLUSIONS: The results indicated that our method improves microRNA biomarker selection by detecting similar microRNA dysregulational synergistic patterns across the multiple subtypes. Since microRNA-target dysregulations are implicated in many cancers, we believe this tool can have broad applications for discovery of novel microRNA biomarkers in heterogeneous cancer diseases.}, } @article {pmid30577740, year = {2018}, author = {Corona, RI and Sudarshan, S and Aluru, S and Guo, JT}, title = {An SVM-based method for assessment of transcription factor-DNA complex models.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {506}, doi = {10.1186/s12859-018-2538-y}, pmid = {30577740}, issn = {1471-2105}, support = {R15 GM110618/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; DNA/chemistry/*metabolism ; *Models, Molecular ; Protein Binding ; *Support Vector Machine ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Atomic details of protein-DNA complexes can provide insightful information for better understanding of the function and binding specificity of DNA binding proteins. In addition to experimental methods for solving protein-DNA complex structures, protein-DNA docking can be used to predict native or near-native complex models. A docking program typically generates a large number of complex conformations and predicts the complex model(s) based on interaction energies between protein and DNA. However, the prediction accuracy is hampered by current approaches to model assessment, especially when docking simulations fail to produce any near-native models.

RESULTS: We present here a Support Vector Machine (SVM)-based approach for quality assessment of the predicted transcription factor (TF)-DNA complex models. Besides a knowledge-based protein-DNA interaction potential DDNA3, we applied several structural features that have been shown to play important roles in binding specificity between transcription factors and DNA molecules to quality assessment of complex models. To address the issue of unbalanced positive and negative cases in the training dataset, we applied hard-negative mining, an iterative training process that selects an initial training dataset by combining all of the positive cases and a random sample from the negative cases. Results show that the SVM model greatly improves prediction accuracy (84.2%) over two knowledge-based protein-DNA interaction potentials, orientation potential (60.8%) and DDNA3 (68.4%). The improvement is achieved through reducing the number of false positive predictions, especially for the hard docking cases, in which a docking algorithm fails to produce any near-native complex models.

CONCLUSIONS: A learning-based SVM scoring model with structural features for specific protein-DNA binding and an atomic-level protein-DNA interaction potential DDNA3 significantly improves prediction accuracy of complex models by successfully identifying cases without near-native structural models.}, } @article {pmid30577739, year = {2018}, author = {Chandrasekaran, S and Stahlberg, E}, title = {Computational approaches for Cancer 2017 workshop overview.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {487}, doi = {10.1186/s12859-018-2502-x}, pmid = {30577739}, issn = {1471-2105}, mesh = {Computational Biology/*methods ; Education ; History, 21st Century ; Humans ; Neoplasms/*diagnosis/pathology ; }, } @article {pmid30577738, year = {2018}, author = {Zhu, X and Shen, X and Jiang, X and Wei, K and He, T and Ma, Y and Liu, J and Hu, X}, title = {Nonlinear expression and visualization of nonmetric relationships in genetic diseases and microbiome data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 20}, pages = {505}, doi = {10.1186/s12859-018-2537-z}, pmid = {30577738}, issn = {1471-2105}, mesh = {Algorithms ; Databases, Genetic ; *Gene Expression Regulation ; Genetic Diseases, Inborn/*genetics ; Humans ; Microbiota/*genetics ; *Nonlinear Dynamics ; Phenotype ; Time Factors ; }, abstract = {BACKGROUND: The traditional methods of visualizing high-dimensional data objects in low-dimensional metric spaces are subject to the basic limitations of metric space. These limitations result in multidimensional scaling that fails to faithfully represent non-metric similarity data.

RESULTS: Multiple maps t-SNE (mm-tSNE) has drawn much attention due to the construction of multiple mappings in low-dimensional space to visualize the non-metric pairwise similarity to eliminate the limitations of a single metric map. mm-tSNE regularization combines the intrinsic geometry between data points in a high-dimensional space. The weight of data points on each map is used as the regularization parameter of the manifold, so the weights of similar data points on the same map are also as close as possible. However, these methods use standard momentum methods to calculate parameters of gradient at each iteration, which may lead to erroneous gradient search directions so that the target loss function fails to achieve a better local minimum. In this article, we use a Nesterov momentum method to learn the target loss function and correct each gradient update by looking back at the previous gradient in the candidate search direction. By using indirect second-order information, the algorithm obtains faster convergence than the original algorithm. To further evaluate our approach from a comparative perspective, we conducted experiments on several datasets including social network data, phenotype similarity data, and microbiomic data.

CONCLUSIONS: The experimental results show that the proposed method achieves better results than several versions of mm-tSNE based on three evaluation indicators including the neighborhood preservation ratio (NPR), error rate and time complexity.}, } @article {pmid30577736, year = {2018}, author = {Wozniak, JM and Jain, R and Balaprakash, P and Ozik, J and Collier, NT and Bauer, J and Xia, F and Brettin, T and Stevens, R and Mohd-Yusof, J and Cardona, CG and Essen, BV and Baughman, M}, title = {CANDLE/Supervisor: a workflow framework for machine learning applied to cancer research.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 18}, pages = {491}, doi = {10.1186/s12859-018-2508-4}, pmid = {30577736}, issn = {1471-2105}, support = {R01 GM115839/GM/NIGMS NIH HHS/United States ; }, mesh = {Early Detection of Cancer/*methods ; Humans ; Machine Learning/*trends ; Neoplasms/*diagnosis/pathology ; Neural Networks (Computer) ; Workflow ; }, abstract = {BACKGROUND: Current multi-petaflop supercomputers are powerful systems, but present challenges when faced with problems requiring large machine learning workflows. Complex algorithms running at system scale, often with different patterns that require disparate software packages and complex data flows cause difficulties in assembling and managing large experiments on these machines.

RESULTS: This paper presents a workflow system that makes progress on scaling machine learning ensembles, specifically in this first release, ensembles of deep neural networks that address problems in cancer research across the atomistic, molecular and population scales. The initial release of the application framework that we call CANDLE/Supervisor addresses the problem of hyper-parameter exploration of deep neural networks.

CONCLUSIONS: Initial results demonstrating CANDLE on DOE systems at ORNL, ANL and NERSC (Titan, Theta and Cori, respectively) demonstrate both scaling and multi-platform execution.}, } @article {pmid30577732, year = {2018}, author = {Dehghannasiri, R and Shahrokh Esfahani, M and Dougherty, ER}, title = {An experimental design framework for Markovian gene regulatory networks under stationary control policy.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {137}, doi = {10.1186/s12918-018-0649-8}, pmid = {30577732}, issn = {1752-0509}, abstract = {BACKGROUND: A fundamental problem for translational genomics is to find optimal therapies based on gene regulatory intervention. Dynamic intervention involves a control policy that optimally reduces a cost function based on phenotype by externally altering the state of the network over time. When a gene regulatory network (GRN) model is fully known, the problem is addressed using classical dynamic programming based on the Markov chain associated with the network. When the network is uncertain, a Bayesian framework can be applied, where policy optimality is with respect to both the dynamical objective and the uncertainty, as characterized by a prior distribution. In the presence of uncertainty, it is of great practical interest to develop an experimental design strategy and thereby select experiments that optimally reduce a measure of uncertainty.

RESULTS: In this paper, we employ mean objective cost of uncertainty (MOCU), which quantifies uncertainty based on the degree to which uncertainty degrades the operational objective, that being the cost owing to undesirable phenotypes. We assume that a number of conditional probabilities characterizing regulatory relationships among genes are unknown in the Markovian GRN. In sum, there is a prior distribution which can be updated to a posterior distribution by observing a regulatory trajectory, and an optimal control policy, known as an "intrinsically Bayesian robust" (IBR) policy. To obtain a better IBR policy, we select an experiment that minimizes the MOCU remaining after applying its output to the network. At this point, we can either stop and find the resulting IBR policy or proceed to determine more unknown conditional probabilities via regulatory observation and find the IBR policy from the resulting posterior distribution. For sequential experimental design this entire process is iterated. Owing to the computational complexity of experimental design, which requires computation of many potential IBR policies, we implement an approximate method utilizing mean first passage times (MFPTs) - but only in experimental design, the final policy being an IBR policy.

CONCLUSIONS: Comprehensive performance analysis based on extensive simulations on synthetic and real GRNs demonstrate the efficacy of the proposed method, including the accuracy and computational advantage of the approximate MFPT-based design.}, } @article {pmid30577731, year = {2018}, author = {Wang, K and Liu, X and Guo, Y and Wu, Z and Zhi, D and Ruan, J and Zhao, Z}, title = {The International Conference on Intelligent Biology and Medicine (ICIBM) 2018: systems biology on diverse data types.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 8}, pages = {125}, doi = {10.1186/s12918-018-0648-9}, pmid = {30577731}, issn = {1752-0509}, abstract = {Between June 10-12, 2018, the International Conference on Intelligent Biology and Medicine (ICIBM 2018) was held in Los Angeles, California, USA. The conference included 11 scientific sessions, four tutorials, one poster session, four keynote talks and four eminent scholar talks that covered a wide range of topics in 3D genome structure analysis and visualization, next generation sequencing analysis, computational drug discovery, medical informatics, cancer genomics and systems biology. Systems biology has been a main theme in ICIBM 2018, with exciting advances presented in many areas of systems biology, covering various different data types such as gene regulation, circular RNAs expression, single-cell RNA-Seq, inter-chromosomal interactions, metabolomics, proteomics and phosphoproteomics. Here, we describe ten high quality papers to be published in BMC Systems Biology.}, } @article {pmid30577728, year = {2018}, author = {Fang, F and Xu, J and Li, Q and Xia, X and Du, G}, title = {Characterization of a Lactobacillus brevis strain with potential oral probiotic properties.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {221}, doi = {10.1186/s12866-018-1369-3}, pmid = {30577728}, issn = {1471-2180}, support = {31771955//National Natural Science Foundation of China/ ; IRT_15R26//Program for Changjiang Scholars and Innovative Research Team/ ; }, abstract = {BACKGROUND: The microflora composition of the oral cavity affects oral health. Some strains of commensal bacteria confer probiotic benefits to the host. Lactobacillus is one of the main probiotic genera that has been used to treat oral infections. The objective of this study was to select lactobacilli with a spectrum of probiotic properties and investigate their potential roles in oral health.

RESULTS: An oral isolate characterized as Lactobacillus brevis BBE-Y52 exhibited antimicrobial activities against Streptococcus mutans, a bacterial species that causes dental caries and tooth decay, and secreted antimicrobial compounds such as hydrogen peroxide and lactic acid. Compared to other bacteria, L. brevis BBE-Y52 was a weak acid producer. Further studies showed that this strain had the capacity to adhere to oral epithelial cells. Co-incubation of L. brevis BBE-Y52 with S. mutans ATCC 25175 increased the IL-10-to-IL-12p70 ratio in peripheral blood mononuclear cells, which indicated that L. brevis BBE-Y52 could alleviate inflammation and might confer benefits to host health by modulating the immune system.

CONCLUSIONS: L. brevis BBE-Y52 exhibited a spectrum of probiotic properties, which may facilitate its applications in oral care products.}, } @article {pmid30576758, year = {2018}, author = {Samolov, E and Mikhailyuk, T and Lukešová, A and Glaser, K and Büdel, B and Karsten, U}, title = {Usual alga from unusual habitats: Biodiversity of Klebsormidium (Klebsormidiophyceae, Streptophyta) from the phylogenetic superclade G isolated from biological soil crusts.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {236-255}, doi = {10.1016/j.ympev.2018.12.018}, pmid = {30576758}, issn = {1095-9513}, abstract = {Seven new species and two varieties of Klebsormidium were described using an integrative approach on the base of 28 strains from the poorly studied phylogenetic superclade G. These strains originated from the unusual and exotic habitats (semi-deserts, semi-arid shrublands, Mediterranean shrub and deciduous vegetation, temperate Araucaria forests, peat bogs, dumps after coal mining, maritime sand dunes etc.) of four continents (Africa, South and North America, and Europe). Molecular phylogenies based on ITS-1,2, rbcL gene and concatenated dataset of ITS-1,2-rbcL, secondary structure of ITS-2, morphology, ecology and biogeography, micrographs and drawings of the investigated strains were assessed. Additionally, phylogeny and morphology of 18 Klebsormidium strains from other lineages isolated from the same localities (different vegetation types of Chile and maritime sand dunes of Germany) were investigated for the comparison with representatives of clade G. Clade G Klebsormidium is characterized by distant phylogenetic position from the other Klebsormidium lineages and prominent morphology: four-lobed chloroplasts and mostly short swollen cells in young culture, compact small pyrenoids, curved or disintegrated filaments, unusual elongation of cells in old culture, formation of specific cluster- and knot-like colonies on agar surface, especially prominent in strains isolated from desert regions, from which the group probably originated. Comparison of Klebsormidium diversity from different biogeographic regions showed that the representatives of clade G are common algae in regions of the southern hemisphere (South Africa and Chile) and rare representatives in terrestrial ecosystems of the northern hemisphere. Further investigation of mostly unstudied territories of the southern hemisphere could bring many surprises and discoveries, leading to a change of the present concept that Klebsormidium is cosmopolitan in distribution.}, } @article {pmid30576627, year = {2018}, author = {Ziegler, AB and Tavosanis, G}, title = {Glycerophospholipids - Emerging players in neuronal dendrite branching and outgrowth.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.009}, pmid = {30576627}, issn = {1095-564X}, abstract = {Dendrites are the input compartment of the neuron, receiving and integrating incoming information. Dendritic trees are often highly complex and branched. Their branch extension and distribution are tightly correlated with their role and interactions within neuronal networks. Thus, intense research has focused on understanding the mechanisms that govern dendrite elaboration. Recent reports highlight the importance of specific lipids for these processes. In particular, glycerophospholipids and several of their interacting proteins are involved in various steps of dendrite growth, including the initiation and elongation of dendritic branches and dendritic spines. The aim of this review is to provide a general overview about which particular lipids are involved in shaping dendrite morphology during neuronal differentiation. Additionally, it summarizes recent studies, which helped to gain insights into the mechanisms by which glycerophospholipids and their associated proteins contribute to establishing correct dendritic morphologies.}, } @article {pmid30576522, year = {2018}, author = {Stolle, E and Pracana, R and Howard, P and Paris, CI and Brown, SJ and Castillo-Carrillo, C and Rossiter, SJ and Wurm, Y}, title = {Degenerative expansion of a young supergene.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy236}, pmid = {30576522}, issn = {1537-1719}, abstract = {Long term suppression of recombination ultimately leads to gene loss, as demonstrated by the depauperate Y and W chromosomes of long-established pairs of XY and ZW chromosomes. The young social supergene of the Solenopsis invicta red fire ant provides a powerful system to examine the effects of suppressed recombination over a shorter timescale. The two variants of this supergene are carried by a pair of heteromorphic chromosomes, referred to as the social B and social b (SB and Sb) chromosomes. The Sb variant of this supergene changes colony social organization and has an inheritance pattern similar to a Y or W chromosome because it is unable to recombine. We used high-resolution optical mapping, k-mer distribution analysis and quantification of repetitive elements on haploid ants carrying alternate variants of this young supergene region. We find that instead of shrinking, the Sb variant of the supergene has increased in length by more than 30%. Surprisingly, only a portion of this length increase is due to consistent increases in the frequency of particular classes of repetitive elements. Instead, haplotypes of this supergene variant differ dramatically in the amounts of other repetitive elements, indicating that the accumulation of repetitive elements is a heterogeneous and dynamic process. This is the first comprehensive demonstration of degenerative expansion in an animal and shows that it occurs through non-linear processes during the early evolution of a region of suppressed recombination.}, } @article {pmid30576032, year = {2018}, author = {Leplongeon, A and Goder-Goldberger, M and Pleurdeau, D}, title = {International workshop on human occupations of the Nile Valley and neighboring regions between 75,000 and 15,000 years ago.}, journal = {Evolutionary anthropology}, volume = {}, number = {}, pages = {}, doi = {10.1002/evan.21756}, pmid = {30576032}, issn = {1520-6505}, } @article {pmid30575503, year = {2018}, author = {Zhu, J and Hong, P and Wang, S and Hu, Z and Wang, H}, title = {Phycocomes zhengii gen. nov., sp. nov., a marine bacterium of the family Rhodobacteraceae isolated from the phycosphere of Chlorella vulgaris.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003194}, pmid = {30575503}, issn = {1466-5034}, abstract = {A Gram-stain-negative, motile with flagellum, ovoid- or rod-shaped, aerobic bacterium, was isolated from the phycosphere of the microalga Chlorellavulgaris and designated as strain LMIT002T. The bacterium formed white, circular and smooth colonies on marine agar 2216 after 48 h incubation at 25 °C. On the basis of 16S rRNA gene sequence analysis, strain LMIT002T was found to be affiliated with the family Rhodobacteraceae of the order Rhodobacterales, and formed a distinct group. The 16S rRNA gene sequence similarities between strain LMIT002T and type strains in the family including Poseidonocella pacifica DSM 29316T, Roseobacter litoralis and Rhodovulum sulfidophilum were 95.1, 95.0 and 95.0 %, respectively. Strain LMIT002Tgrew optimally at 25 °C, pH 6.0 and in the presence of 2.0 % (w/v) NaCl. The genomic DNA G+C content was 67.0 mol% (the thermal denaturation method) or 66.9 % (genome sequencing). The sole respiratory quinone was ubiquinone-8, while the major fatty acids were summed feature 8 (C18 : 1 ω7с/C18 : 1 ω6с). The draft genome of strain LMIT002T was sequenced and annotated, with the results showing that it had a total size of 4 607 780 bp and comprised 4557 genes. Functional genes encoding the production of vitamin B12, indole-3-acetic acid and transform dimethylsulphoniopropionate were detected. Given its distinct genomic, morphological and physiological differences from previously described type strains, strain LMIT002T is proposed as a representative of a novel genus of the family Rhodobacteraceae, with the name Phycocomes zhengii gen. nov., sp. nov. The type strain is LMIT002T (=KCTC 62390T=CICC 24357T).}, } @article {pmid30575502, year = {2018}, author = {Cheng, LJ and Ming, H and Zhao, ZL and Ji, WL and Zhang, LY and Li, LY and Meng, XL and Li, M and Niu, MM and Nie, GX}, title = {Microbacterium ureisolvens sp. nov., isolated from a Yellow River sample.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003203}, pmid = {30575502}, issn = {1466-5034}, abstract = {A Gram-stain positive, aerobic, non-motile and short-rod-shaped strain, CFH S00084T, was isolated from a sediment sample of the Yellow River in Henan Province, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CFH S00084T clustered within members of Microbacterium and was most closely related to the type strains Microbacterium yannicii JCM 18959T and Microbacterium arthrosphaerae DSM 22421T (98.97 % and 98.36 % similarity, respectively). The strain grew optimally at 25-37 °C, at pH 7.0 and in 0-3 % (w/v) NaCl. The major whole-cell sugars were rhamnose and glucose. The cell-wall peptidoglycan mainly contained glycine, alanine and ornithine. The menaquinones of strain CFH S00084T were MK-13, MK-12 and MK-11. The major fatty acids detected were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The genome of strain CFH S00084T was 4.03 Mbp with a G+C content of 70.5 mol%. The average nucleotide identity (ANI) and digital DNA-DNA hybridization (dDDH) values between CFH S00084T and the other species of the genus Microbacterium were found to be low (ANIm <85 %, ANIb <75 % and dDDH <24 %). The phylogenomic analysis provided evidence for clear phylogenetic divergence between strain CFH S00084T and its closely related type strains. On the basis of the differential physiological properties, chemotaxonomic characteristics and low ANI and dDDH results, strain CFH S00084T is considered to represent a novel species for which the name Microbacteriumureisolvens sp. nov. is proposed. The type strain is CFH S00084T (=KCTC 39802T=DSM 103157T).}, } @article {pmid30575501, year = {2018}, author = {Liang, Y and Tang, K and Wang, Y and Yuan, B and Tan, F and Feng, F and Liu, H}, title = {Hymenobacter crusticola sp. nov., isolated from biological soil crust.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003196}, pmid = {30575501}, issn = {1466-5034}, abstract = {A Gram-stain-negative, aerobic, light-pink, short rod-shaped, non-spore-forming bacterial strain was isolated from biological soil crust sampled in the Hopq Desert, Inner Mongolia, China, designated MIMBbqt21T. The G+C content of the genomic DNA was 55.1 mol%. Phylogenetic analysis of the 16S rRNA gene sequence showed that strain MIMBbqt21T belonged to the genus Hymenobacter and had the highest sequence similarity to Hymenobacter cavernaeK1E01-27T (94.35 %). Cell growth could be observed at 4-29 °C (optimum, 24 °C), pH of 6.0-8.6 (optimum, 6.0) and in the presence of 1 % (w/v) NaCl (optimum, 0 %). The major fatty acids of strain MIMBbqt21T were iso-C15 : 0, C16 : 1ω5c and summed feature 3 (C16 : 1ω7c/C16 : 1ω6c). The main polar lipids were phosphatidylethanolamine, five unidentified aminophospholipids, an unidentified glycolipid and four unidentified polar lipids. The sole respiratory quinone was menaquinone MK-7. Based on the results of the phylogenetic, chemotaxonomic and phenotypic studies, strain MIMBbqt21T could be distinguished from all known Hymenobacter species and represents a novel species, for which the name Hymenobactercrusticola sp. nov. is proposed. The type strain is MIMBbqt21T (=MCCC 1K01312T=KCTC 42804T).}, } @article {pmid30575500, year = {2018}, author = {Tindall, BJ}, title = {An analysis of the term 'standing in nomenclature', as used in the International Code of Nomenclature of Prokaryotes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003191}, pmid = {30575500}, issn = {1466-5034}, abstract = {The term 'standing in nomenclature' is used in several instances in the International Code of Nomenclature of Prokaryotes, but the term is not defined. An analysis of the way the term has been used in the past and the context in which it is currently used indicates that it may be more appropriate to substitute the term with more suitable wording that is consistent with usage in other parts of the Code.}, } @article {pmid30575499, year = {2018}, author = {Baek, K and Song, J and Cho, JC and Chung, EJ and Choi, A}, title = {Nibricoccus aquaticus gen. nov., sp. nov., a new genus of the family Opitutaceae isolated from hyporheic freshwater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003198}, pmid = {30575499}, issn = {1466-5034}, abstract = {A yellow-coloured, Gram-strain-negative, non-motile, cocci-shaped, strictly aerobic bacterium, designated HZ-65T, was isolated from hyporheic freshwater in the Republic of Korea. Strain HZ-65T grew at 15-37 °C (optimum, 25-30 °C), pH 5.5-9.0 (optimum, pH 7.0) and 0-0.5 % NaCl (w/v; optimum at 0 % NaCl). Phylogenetic analysis based on the 16S rRNA gene showed that strain HZ-65T is a member of family Opitutaceae and is closely related to Opitutus terrae PB90-1T (94.0 % similarity), Cephaloticoccus primus CAG34T (93.0 %), and Cephaloticoccus capnophilus CV41T (92.7 %), while the similarities to other Opitutaceae-type strains were lower than 90.0 %. The DNA G+C content was 62.2 mol% and the quinone present was menaquinone-7. The predominant fatty acids were iso-C14 : 0, anteiso-C15 : 0, C16 : 0, and iso-C16 : 0, representing 70 % of the total fatty acids. The major polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. Analysis of the HZ-65T genome revealed the presence of 300 genes that are involved in carbohydrate-active enzymes, which indicates the metabolic potential to degrade polysaccharides. The phenotypic, chemotaxonomic, genetic, and phylogenetic properties suggest that strain HZ-65T represents a novel species in a new genus within the family Opitutaceae, for which the name Nibricoccus aquaticus gen. nov., sp. nov., is proposed. The type strain of Nibricoccus aquaticus is HZ-65T (KACC 19333T=NBRC 112907T).}, } @article {pmid30573849, year = {2018}, author = {Schulz, KN and Harrison, MM}, title = {Mechanisms regulating zygotic genome activation.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41576-018-0087-x}, pmid = {30573849}, issn = {1471-0064}, abstract = {Following fertilization, the two specified gametes must unite to create an entirely new organism. The genome is initially transcriptionally quiescent, allowing the zygote to be reprogrammed into a totipotent state. Gradually, the genome is activated through a process known as the maternal-to-zygotic transition, which enables zygotic gene products to replace the maternal supply that initiated development. This essential transition has been broadly characterized through decades of research in several model organisms. However, we still lack a full mechanistic understanding of how genome activation is executed and how this activation relates to the reprogramming of the zygotic chromatin architecture. Recent work highlights the central role of transcriptional activators and suggests that these factors may coordinate transcriptional activation with other developmental changes.}, } @article {pmid30573631, year = {2018}, author = {Radošević, K}, title = {Forced to change-for good.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1442}, doi = {10.1126/science.362.6421.1442}, pmid = {30573631}, issn = {1095-9203}, } @article {pmid30573630, year = {2018}, author = {Schöneberg, J and Pavlin, MR and Yan, S and Righini, M and Lee, IH and Carlson, LA and Bahrami, AH and Goldman, DH and Ren, X and Hummer, G and Bustamante, C and Hurley, JH}, title = {ATP-dependent force generation and membrane scission by ESCRT-III and Vps4.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1423-1428}, doi = {10.1126/science.aat1839}, pmid = {30573630}, issn = {1095-9203}, support = {R01 AI112442/AI/NIAID NIH HHS/United States ; T32 GM008295/GM/NIGMS NIH HHS/United States ; R56 AI127809/AI/NIAID NIH HHS/United States ; R01 GM032543/GM/NIGMS NIH HHS/United States ; }, abstract = {The endosomal sorting complexes required for transport (ESCRTs) catalyze reverse-topology scission from the inner face of membrane necks in HIV budding, multivesicular endosome biogenesis, cytokinesis, and other pathways. We encapsulated ESCRT-III subunits Snf7, Vps24, and Vps2 and the AAA+ ATPase (adenosine triphosphatase) Vps4 in giant vesicles from which membrane nanotubes reflecting the correct topology of scission could be pulled. Upon ATP release by photo-uncaging, this system generated forces within the nanotubes that led to membrane scission in a manner dependent upon Vps4 catalytic activity and Vps4 coupling to the ESCRT-III proteins. Imaging of scission revealed Snf7 and Vps4 puncta within nanotubes whose presence followed ATP release, correlated with force generation and nanotube constriction, and preceded scission. These observations directly verify long-standing predictions that ATP-hydrolyzing assemblies of ESCRT-III and Vps4 sever membranes.}, } @article {pmid30573629, year = {2018}, author = {Ruscetti, M and Leibold, J and Bott, MJ and Fennell, M and Kulick, A and Salgado, NR and Chen, CC and Ho, YJ and Sanchez-Rivera, FJ and Feucht, J and Baslan, T and Tian, S and Chen, HA and Romesser, PB and Poirier, JT and Rudin, CM and de Stanchina, E and Manchado, E and Sherr, CJ and Lowe, SW}, title = {NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1416-1422}, doi = {10.1126/science.aas9090}, pmid = {30573629}, issn = {1095-9203}, support = {P01 CA129243/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U54 OD020355/OD/NIH HHS/United States ; T32 CA160001/CA/NCI NIH HHS/United States ; K12 CA184746/CA/NCI NIH HHS/United States ; U54 OD020355/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Molecularly targeted therapies aim to obstruct cell autonomous programs required for tumor growth. We show that mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 4/6 inhibitors act in combination to suppress the proliferation of KRAS-mutant lung cancer cells while simultaneously provoking a natural killer (NK) cell surveillance program leading to tumor cell death. The drug combination, but neither agent alone, promotes retinoblastoma (RB) protein-mediated cellular senescence and activation of the immunomodulatory senescence-associated secretory phenotype (SASP). SASP components tumor necrosis factor-α and intercellular adhesion molecule-1 are required for NK cell surveillance of drug-treated tumor cells, which contributes to tumor regressions and prolonged survival in a KRAS-mutant lung cancer mouse model. Therefore, molecularly targeted agents capable of inducing senescence can produce tumor control through non-cell autonomous mechanisms involving NK cell surveillance.}, } @article {pmid30573628, year = {2018}, author = {Blomenkemper, P and Kerp, H and Abu Hamad, A and DiMichele, WA and Bomfleur, B}, title = {A hidden cradle of plant evolution in Permian tropical lowlands.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1414-1416}, doi = {10.1126/science.aau4061}, pmid = {30573628}, issn = {1095-9203}, abstract = {The latitudinal biodiversity gradient today has deep roots in the evolutionary history of Earth's biota over geologic time. In the marine realm, earliest fossil occurrences at low latitudes reveal a tropical cradle for many animal groups. However, the terrestrial fossil record-especially from drier environments that are thought to drive evolutionary innovation-is sparse. We present mixed plant-fossil assemblages from Permian equatorial lowlands in present-day Jordan that harbor precocious records of three major seed-plant lineages that all became dominant during the Mesozoic, including the oldest representative of any living conifer family. These finds offer a glimpse of the early evolutionary origins of modern plant groups in disturbance-prone tropical habitats that are usually hidden from observation.}, } @article {pmid30573627, year = {2018}, author = {Park, PS and Blumenstock, JE and Macy, MW}, title = {The strength of long-range ties in population-scale social networks.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1410-1413}, doi = {10.1126/science.aau9735}, pmid = {30573627}, issn = {1095-9203}, abstract = {Long-range connections that span large social networks are widely assumed to be weak, composed of sporadic and emotionally distant relationships. However, researchers historically have lacked the population-scale network data needed to verify the predicted weakness. Using data from 11 culturally diverse population-scale networks on four continents-encompassing 56 million Twitter users and 58 million mobile phone subscribers-we find that long-range ties are nearly as strong as social ties embedded within a small circle of friends. These high-bandwidth connections have important implications for diffusion and social integration.}, } @article {pmid30573626, year = {2018}, author = {Orosa-Puente, B and Leftley, N and von Wangenheim, D and Banda, J and Srivastava, AK and Hill, K and Truskina, J and Bhosale, R and Morris, E and Srivastava, M and Kümpers, B and Goh, T and Fukaki, H and Vermeer, JEM and Vernoux, T and Dinneny, JR and French, AP and Bishopp, A and Sadanandom, A and Bennett, MJ}, title = {Root branching toward water involves posttranslational modification of transcription factor ARF7.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1407-1410}, doi = {10.1126/science.aau3956}, pmid = {30573626}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Plants adapt to heterogeneous soil conditions by altering their root architecture. For example, roots branch when in contact with water by using the hydropatterning response. We report that hydropatterning is dependent on auxin response factor ARF7. This transcription factor induces asymmetric expression of its target gene LBD16 in lateral root founder cells. This differential expression pattern is regulated by posttranslational modification of ARF7 with the small ubiquitin-like modifier (SUMO) protein. SUMOylation negatively regulates ARF7 DNA binding activity. ARF7 SUMOylation is required to recruit the Aux/IAA (indole-3-acetic acid) repressor protein IAA3. Blocking ARF7 SUMOylation disrupts IAA3 recruitment and hydropatterning. We conclude that SUMO-dependent regulation of auxin response controls root branching pattern in response to water availability.}, } @article {pmid30573625, year = {2018}, author = {Dureuil, M and Boerder, K and Burnett, KA and Froese, R and Worm, B}, title = {Elevated trawling inside protected areas undermines conservation outcomes in a global fishing hot spot.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1403-1407}, doi = {10.1126/science.aau0561}, pmid = {30573625}, issn = {1095-9203}, abstract = {Marine protected areas (MPAs) are increasingly used as a primary tool to conserve biodiversity. This is particularly relevant in heavily exploited fisheries hot spots such as Europe, where MPAs now cover 29% of territorial waters, with unknown effects on fishing pressure and conservation outcomes. We investigated industrial trawl fishing and sensitive indicator species in and around 727 MPAs designated by the European Union. We found that 59% of MPAs are commercially trawled, and average trawling intensity across MPAs is at least 1.4-fold higher as compared with nonprotected areas. Abundance of sensitive species (sharks, rays, and skates) decreased by 69% in heavily trawled areas. The widespread industrial exploitation of MPAs undermines global biodiversity conservation targets, elevating recent concerns about growing human pressures on protected areas worldwide.}, } @article {pmid30573624, year = {2018}, author = {Nagaoka, Y and Zhu, H and Eggert, D and Chen, O}, title = {Single-component quasicrystalline nanocrystal superlattices through flexible polygon tiling rule.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1396-1400}, doi = {10.1126/science.aav0790}, pmid = {30573624}, issn = {1095-9203}, abstract = {Quasicrystalline superlattices (QC-SLs) generated from single-component colloidal building blocks have been predicted by computer simulations but are challenging to reproduce experimentally. We discovered that 10-fold QC-SLs could self-organize from truncated tetrahedral quantum dots with anisotropic patchiness. Transmission electron microscopy and tomography measurements allow structural reconstruction of the QC-SL from the nanoscale packing to the atomic-scale orientation alignments. The unique QC order leads to a tiling concept, the "flexible polygon tiling rule," that replicates the experimental observations. The keys for the single-component QC-SL formation were identified to be the anisotropic shape and patchiness of the building blocks and the assembly microscopic environment. Our discovery may spur the creation of various superstructures using anisotropic objects through an enthalpy-driven route.}, } @article {pmid30573623, year = {2018}, author = {Rocha, JC and Peterson, G and Bodin, Ö and Levin, S}, title = {Cascading regime shifts within and across scales.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1379-1383}, doi = {10.1126/science.aat7850}, pmid = {30573623}, issn = {1095-9203}, abstract = {Regime shifts are large, abrupt, and persistent critical transitions in the function and structure of ecosystems. Yet, it is unknown how these transitions will interact, whether the occurrence of one will increase the likelihood of another or simply correlate at distant places. We explored two types of cascading effects: Domino effects create one-way dependencies, whereas hidden feedbacks produce two-way interactions. We compare them with the control case of driver sharing, which can induce correlations. Using 30 regime shifts described as networks, we show that 45% of regime shift pairwise combinations present at least one plausible structural interdependence. The likelihood of cascading effects depends on cross-scale interactions but differs for each type. Management of regime shifts should account for potential connections.}, } @article {pmid30573622, year = {2018}, author = {Cheung, H and Wang, Y and Biggs, D}, title = {China's reopened rhino horn trade.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1369}, doi = {10.1126/science.aav9392}, pmid = {30573622}, issn = {1095-9203}, } @article {pmid30573621, year = {2018}, author = {Harrison, I and Abell, R and Darwall, W and Thieme, ML and Tickner, D and Timboe, I}, title = {The freshwater biodiversity crisis.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1369}, doi = {10.1126/science.aav9242}, pmid = {30573621}, issn = {1095-9203}, } @article {pmid30573620, year = {2018}, author = {Liu, J and Milne, RI and Cadotte, MW and Wu, ZY and Provan, J and Zhu, GF and Gao, LM and Li, DZ}, title = {Protect Third Pole's fragile ecosystem.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1368}, doi = {10.1126/science.aaw0443}, pmid = {30573620}, issn = {1095-9203}, } @article {pmid30573619, year = {2018}, author = {Reddie, AW and Goldblum, BL and Lakkaraju, K and Reinhardt, J and Nacht, M and Epifanovskaya, L}, title = {Next-generation wargames.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1362-1364}, doi = {10.1126/science.aav2135}, pmid = {30573619}, issn = {1095-9203}, } @article {pmid30573618, year = {2018}, author = {Brogi, M}, title = {Escaping atmospheres of extrasolar planets.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1360-1361}, doi = {10.1126/science.aav7010}, pmid = {30573618}, issn = {1095-9203}, mesh = {Atmosphere ; Exobiology ; Extraterrestrial Environment ; *Helium ; Neptune ; *Planets ; }, } @article {pmid30573617, year = {2018}, author = {Padmanabhan, A and Haldar, SM}, title = {Unusual transcription factor protects against heart failure.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1359-1360}, doi = {10.1126/science.aav8956}, pmid = {30573617}, issn = {1095-9203}, mesh = {*Heart Failure ; Humans ; Membrane Proteins ; *Transcription Factors ; }, } @article {pmid30573616, year = {2018}, author = {Giehl, RFH and von Wirén, N}, title = {Hydropatterning-how roots test the waters.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1358-1359}, doi = {10.1126/science.aav9375}, pmid = {30573616}, issn = {1095-9203}, mesh = {Gene Expression Regulation ; *Plant Roots ; Protein Processing, Post-Translational ; *Transcription Factors ; }, } @article {pmid30573615, year = {2018}, author = {Scheffer, M and van Nes, EH}, title = {Seeing a global web of connected systems.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1357}, doi = {10.1126/science.aav8478}, pmid = {30573615}, issn = {1095-9203}, mesh = {Animals ; *Ecosystem ; Humans ; *Social Conditions ; }, } @article {pmid30573614, year = {2018}, author = {Cornen, S and Vivier, E}, title = {Chemotherapy and tumor immunity.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1355-1356}, doi = {10.1126/science.aav7871}, pmid = {30573614}, issn = {1095-9203}, mesh = {*Apoptosis ; Drug Combinations ; Humans ; Killer Cells, Natural ; *Neoplasms ; }, } @article {pmid30573613, year = {2018}, author = {Wu, S and Sun, Y}, title = {Tessellating tiny tetrahedrons.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1354-1355}, doi = {10.1126/science.aav8597}, pmid = {30573613}, issn = {1095-9203}, mesh = {*Nanoparticles ; }, } @article {pmid30573612, year = {2018}, author = {Voosen, P and Escobar, H and Enserink, M}, title = {Breakdowns of the year.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1352-1353}, doi = {10.1126/science.362.6421.1352}, pmid = {30573612}, issn = {1095-9203}, } @article {pmid30573611, year = {2018}, author = {Hand, E and Vogel, G and Garber, K and Kaiser, J and Servick, K and Clery, D and Service, RF and Wadman, M}, title = {Runners-up.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1346-1351}, doi = {10.1126/science.362.6421.1346}, pmid = {30573611}, issn = {1095-9203}, } @article {pmid30573610, year = {2018}, author = {Pennisi, E}, title = {Development cell by cell.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1344-1345}, doi = {10.1126/science.362.6421.1344}, pmid = {30573610}, issn = {1095-9203}, } @article {pmid30573609, year = {2018}, author = {Cho, A}, title = {National Academies urges renewed commitment to fusion.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1343}, doi = {10.1126/science.362.6421.1343}, pmid = {30573609}, issn = {1095-9203}, } @article {pmid30573608, year = {2018}, author = {Stokstad, E}, title = {'Five Deeps' mission to explore mysterious ocean trenches.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1342-1343}, doi = {10.1126/science.362.6421.1342}, pmid = {30573608}, issn = {1095-9203}, } @article {pmid30573607, year = {2018}, author = {Spinney, L}, title = {Link to Alzheimer's seen in nodding syndrome.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1341}, doi = {10.1126/science.362.6421.1341}, pmid = {30573607}, issn = {1095-9203}, } @article {pmid30573606, year = {2018}, author = {Pennisi, E}, title = {Fossils push back origin of key plant groups millions of years.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1340}, doi = {10.1126/science.362.6421.1340}, pmid = {30573606}, issn = {1095-9203}, } @article {pmid30573605, year = {2018}, author = {Voosen, P}, title = {Antarctic ice melt 125,000 years ago offers warning.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1339}, doi = {10.1126/science.362.6421.1339}, pmid = {30573605}, issn = {1095-9203}, } @article {pmid30573604, year = {2018}, author = {Wade, L}, title = {Universities 'held hostage' in Nicaragua's political crisis.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1338}, doi = {10.1126/science.362.6421.1338}, pmid = {30573604}, issn = {1095-9203}, } @article {pmid30573603, year = {2018}, author = {Clery, D}, title = {Hints of young planets puzzle theorists.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1337}, doi = {10.1126/science.362.6421.1337}, pmid = {30573603}, issn = {1095-9203}, } @article {pmid30573602, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1334-1336}, doi = {10.1126/science.362.6421.1334}, pmid = {30573602}, issn = {1095-9203}, } @article {pmid30573601, year = {2018}, author = {Berg, J}, title = {Exploring organisms cell by cell.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1333}, doi = {10.1126/science.aaw3633}, pmid = {30573601}, issn = {1095-9203}, } @article {pmid30573546, year = {2018}, author = {Tokatlian, T and Read, BJ and Jones, CA and Kulp, DW and Menis, S and Chang, JYH and Steichen, JM and Kumari, S and Allen, JD and Dane, EL and Liguori, A and Sangesland, M and Lingwood, D and Crispin, M and Schief, WR and Irvine, DJ}, title = {Innate immune recognition of glycans targets HIV nanoparticle immunogens to germinal centers.}, journal = {Science (New York, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.1126/science.aat9120}, pmid = {30573546}, issn = {1095-9203}, abstract = {In vaccine design, arraying antigens in a multivalent nanoparticle form is often employed, but in vivo mechanisms underlying the enhanced immunity elicited by such vaccines remain poorly understood. Here we compared the fate of two different heavily glycosylated HIV antigens, a gp120-derived mini-protein and a large, stabilized envelope trimer, in protein nanoparticle or "free" forms following primary immunization. Unlike monomeric antigens, nanoparticles were rapidly shuttled to the follicular dendritic cell (FDC) network and then concentrated in germinal centers in a complement-, mannose-binding lectin (MBL)-, and immunogen glycan-dependent manner. Loss of FDC localization in MBL-deficient mice or via immunogen deglycosylation significantly impacted antibody responses. These findings identify an innate immune-mediated recognition pathway promoting antibody responses to particulate antigens, with broad implications for humoral immunity and vaccine design.}, } @article {pmid30573545, year = {2019}, author = {Schuller, JM and Birrell, JA and Tanaka, H and Konuma, T and Wulfhorst, H and Cox, N and Schuller, SK and Thiemann, J and Lubitz, W and Sétif, P and Ikegami, T and Engel, BD and Kurisu, G and Nowaczyk, MM}, title = {Structural adaptations of photosynthetic complex I enable ferredoxin-dependent electron transfer.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6424}, pages = {257-260}, doi = {10.1126/science.aau3613}, pmid = {30573545}, issn = {1095-9203}, abstract = {Photosynthetic complex I enables cyclic electron flow around photosystem I, a regulatory mechanism for photosynthetic energy conversion. We report a 3.3-angstrom-resolution cryo-electron microscopy structure of photosynthetic complex I from the cyanobacterium Thermosynechococcus elongatus. The model reveals structural adaptations that facilitate binding and electron transfer from the photosynthetic electron carrier ferredoxin. By mimicking cyclic electron flow with isolated components in vitro, we demonstrate that ferredoxin directly mediates electron transfer between photosystem I and complex I, instead of using intermediates such as NADPH (the reduced form of nicotinamide adenine dinucleotide phosphate). A large rate constant for association of ferredoxin to complex I indicates efficient recognition, with the protein subunit NdhS being the key component in this process.}, } @article {pmid30573544, year = {2019}, author = {Welin, ER and Ngamnithiporn, A and Klatte, M and Lapointe, G and Pototschnig, GM and McDermott, MSJ and Conklin, D and Gilmore, CD and Tadross, PM and Haley, CK and Negoro, K and Glibstrup, E and Grünanger, CU and Allan, KM and Virgil, SC and Slamon, DJ and Stoltz, BM}, title = {Concise total syntheses of (-)-jorunnamycin A and (-)-jorumycin enabled by asymmetric catalysis.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6424}, pages = {270-275}, doi = {10.1126/science.aav3421}, pmid = {30573544}, issn = {1095-9203}, abstract = {The bis-tetrahydroisoquinoline (bis-THIQ) natural products have been studied intensively over the past four decades for their exceptionally potent anticancer activity, in addition to strong Gram-positive and Gram-negative antibiotic character. Synthetic strategies toward these complex polycyclic compounds have relied heavily on electrophilic aromatic chemistry, such as the Pictet-Spengler reaction, that mimics their biosynthetic pathways. Herein, we report an approach to two bis-THIQ natural products, jorunnamycin A and jorumycin, that instead harnesses the power of modern transition-metal catalysis for the three major bond-forming events and proceeds with high efficiency (15 and 16 steps, respectively). By breaking from biomimicry, this strategy allows for the preparation of a more diverse set of nonnatural analogs.}, } @article {pmid30573371, year = {2018}, author = {De Cesare, S}, title = {Disentangling organic and technological progress: An epistemological clarification introducing a key distinction between two levels of axiology.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.shpsc.2018.10.011}, pmid = {30573371}, issn = {1879-2499}, abstract = {The notion of "progress" can be defined as a directional change towards the better, implying both a descriptive and an axiological element. "Organic progress" refers to this notion applied to the history of life, whereas "technological progress" refers to this notion applied to the history of technological artifacts. This paper aims to disentangle conceptual questions about the notion of organic progress with respect to evolutionary theory, by proposing an epistemological perspective that also accounts for technological progress. My argument is set out in four sections. In section 2, drawing on the thought of some eminent evolutionary biologists, I will pinpoint a theoretical claim according to which a specific notion of organic progress is consistent with evolutionary theory. In section 3, I show some limits and problems that arise in the application of this theoretical claim to the organic domain. In section 4, I consider why these problems with application are often underestimated: I hypothesize that this is linked to the analogy frequently made between organic and technological progress. Finally, in section 5, I will carry on the analysis of this analogy by proposing a distinction between two levels of axiology. I claim that this distinction avoids several common confusions when talking about progress.}, } @article {pmid30573193, year = {2019}, author = {Campbell, HA and Micheli-Campbell, MA and Udyawer, V}, title = {Early Career Researchers Embrace Data Sharing.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {2}, pages = {95-98}, doi = {10.1016/j.tree.2018.11.010}, pmid = {30573193}, issn = {1872-8383}, abstract = {A request for raw data from the corresponding authors of 771 animal biotelemetry-focused manuscripts, published between 1995 and 2015, highlighted a difference in data sharing practices across researcher career levels. Responses were positive in only 11% of requests made to corresponding authors (CAs) that were senior researchers, while 72% of responses were positive when CAs were early career researchers (ECRs), demonstrating that the majority of senior researchers perceived little benefit from the public data archiving of their published research, while they often remain the data custodian.}, } @article {pmid30573175, year = {2018}, author = {Stone, W and Bousema, T and Sauerwein, R and Drakeley, C}, title = {Two-Faced Immunity? The Evidence for Antibody Enhancement of Malaria Transmission.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.003}, pmid = {30573175}, issn = {1471-5007}, abstract = {Plasmodium gametocytes can induce an immune response in humans that interferes with the development of sexual-stage parasites in the mosquito gut. Many early studies of the sexual-stage immune response noted that mosquito infection could be enhanced as well as reduced by immune sera. For Plasmodium falciparum, these reports are scarce, and the phenomenon is generally regarded as a methodological artefact. Plasmodium transmission enhancement (TE) remains contentious, but the clinical development of transmission-blocking vaccines based on sexual-stage antigens requires that it is further studied. In this essay, we review the early literature on the sexual-stage immune response and transmission-modulating immunity. We discuss hypotheses for the mechanism of TE, suggest experiments to prove or disprove its existence, and discuss its possible implications.}, } @article {pmid30572961, year = {2018}, author = {Popovic, A and Bourdon, C and Wang, PW and Guttman, DS and Voskuijl, W and Grigg, ME and Bandsma, RHJ and Parkinson, J}, title = {Design and application of a novel two-amplicon approach for defining eukaryotic microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {228}, doi = {10.1186/s40168-018-0612-3}, pmid = {30572961}, issn = {2049-2618}, support = {DG-06664//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {BACKGROUND: Due to a lack of systematic diagnostics, our understanding of the diversity and role of eukaryotic microbiota in human health is limited. While studies have shown fungal communities to be significant modulators of human health, information on the prevalence of taxa such as protozoa and helminths has been limited to a small number of species for which targeted molecular diagnostics are available. To probe the diversity of eukaryotic microbes and their relationships with other members of the microbiota, we applied in silico and experimental approaches to design a novel two-amplicon surveillance tool, based on sequencing regions of ribosomal RNA genes and their internal transcribed spacers. We subsequently demonstrated the utility of our approach by characterizing the eukaryotic microbiota of 46 hospitalized Malawian children suffering from Severe Acute Malnutrition (SAM).

RESULTS: Through in silico analysis and validation on a diverse panel of eukaryotes, we identified 18S rRNA variable genetic regions 4 and 5 (18S V4 V5), together with a region encoding 28S rRNA variable genetic region 2 and the internal transcribed spacers (transITS), as optimal for the systematic classification of eukaryotes. Sequencing of these regions revealed protozoa in all stool samples from children with SAM and helminths in most, including several eukaryotes previously implicated in malnutrition and diarrheal disease. Clinical comparisons revealed no association between protozoan parasites and diarrhea or HIV reactivity. However, the presence of Blastocystis correlated with bacterial alpha diversity and increased abundance of specific taxa, including Sporobacter, Cellulosibacter, Oscillibacter, and Roseburia.

CONCLUSION: We suggest this novel two-amplicon based strategy will prove an effective tool to deliver new insights into the role of eukaryotic microbiota in health and disease.}, } @article {pmid30572950, year = {2018}, author = {Bianco, A and Valletti, A and Longo, G and Bisceglia, L and Montoya, J and Emperador, S and Guerriero, S and Petruzzella, V}, title = {Mitochondrial DNA copy number in affected and unaffected LHON mutation carriers.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {911}, doi = {10.1186/s13104-018-4025-y}, pmid = {30572950}, issn = {1756-0500}, abstract = {OBJECTIVES: Leber's hereditary optic neuropathy (LHON) is a mitochondrial genetic disease characterized by a variable and reduced penetrance. Individuals carrying a primary LHON-causing mitochondrial DNA (mtDNA) mutation may either remain asymptomatic lifelong, as unaffected carriers, or develop sudden central visual loss that rapidly aggravates over some weeks. Over the years several genetic/environmental triggers able to modulate the risk of developing LHON have been proposed. We provided data supporting a possible correlation between LHON penetrance and the mtDNA copy number, a raw index of mitochondrial mass, whose increase could represent a compensatory response that cells implement to alleviate the pathogenic effect of the primary LHON-causing mtDNA mutations.

DATA DESCRIPTION: We collected Italian and Spanish subjects harboring one of the three common LHON primary mutations, either in heteroplasmic or homoplasmic status. For each population we were able to discriminate between affected subjects presenting typical clinical tracts of LHON and LHON-causing mutation carriers showing no symptoms correlated with vision loss. Each subject has been characterized for the presence of a LHON primary mutation, for its status of homoplasmy or heteroplasmy, and for the mtDNA content per cell, expressed as relative mtDNA/nDNA ratio respect to controls. Additional clinical information is present for all the Italian subjects.}, } @article {pmid30572943, year = {2018}, author = {Thota, S and Srivastav, VK}, title = {Quadratically convergent algorithm for computing real root of non-linear transcendental equations.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {909}, doi = {10.1186/s13104-018-4008-z}, pmid = {30572943}, issn = {1756-0500}, abstract = {OBJECTIVES: The present paper describes a new algorithm to find a root of non-linear transcendental equations. It is found that Regula-Falsi method always gives guaranteed result but slow convergence. However, Newton-Raphson method does not give guaranteed result but faster than Regula-Falsi method. Therefore, the present paper used these two ideas and developed a new algorithm which has better convergence than Regula-Falsi and guaranteed result. One of the major issue in Newton-Raphson method is, it fails when first derivative is zero or approximately zero.

RESULTS: The proposed method implemented the failure condition of Newton-Raphson method with better convergence. Error calculation has been discussed for certain real life examples using Bisection, Regula-Falsi, Newton-Raphson method and new proposed method. The computed results show that the new proposed quadratically convergent method provides better convergence than other methods.}, } @article {pmid30572937, year = {2018}, author = {Talavera-López, C and Capuccini, B and Mitter, R and Lin, JW and Langhorne, J}, title = {Transcriptomes of microglia in experimental cerebral malaria in mice in the presence and absence of Type I Interferon signaling.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {913}, doi = {10.1186/s13104-018-4020-3}, pmid = {30572937}, issn = {1756-0500}, support = {FC001101//Francis Crick Institute/ ; FC001101//Wellcome Trust/United Kingdom ; }, abstract = {OBJECTIVES: Plasmodium berghei ANKA infection in mice is a model for human cerebral malaria, the most severe complication of Plasmodium falciparum infection. Responses of brain microglia have been little investigated, and may contribute to the pathogenesis of cerebral malaria. We showed previously that microglia are activated in P. berghei infections, and that Type 1-Interferon signaling is important for activation. This dataset compares transcriptomic profiles of brain microglia of infected mice in the presence and absence of Type 1 interferon signaling, with the aim of identifying genes in microglia in this pathway during experimental cerebral malaria.

DATA DESCRIPTION: We documented global gene expression from microglial RNA from uninfected and P berghei-infected wild-type C57BL/6 and IFNA Receptor Knock-out mice using Illumina Beadarrays. Principal component analysis showed 4 groups of samples corresponding to naïve wild-type, naïve IFNA Receptor knock-out, infected wild-type, and IFNA Receptor knock-out mice. Differentially-expressed genes of microglia from the two groups of infected mice are documented. Gene set enrichment analysis showing the top 500 genes assigned to Reactome pathways from infected IFNA Receptor knock-out versus naïve, and infected WT versus naïve has been generated. These data will be useful for those interested in microglia cells, and in experimental cerebral malaria.}, } @article {pmid30572934, year = {2018}, author = {Hasson, CJ and Kent, JA and Caldwell, GE}, title = {Magnetic resonance images and measurements of the volume, proportion, and longitudinal distribution of contractile and non-contractile tissue in the dorsi- and plantar flexor muscles of healthy young and older adults.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {910}, doi = {10.1186/s13104-018-4026-x}, pmid = {30572934}, issn = {1756-0500}, support = {R03AG026281//National Institute on Aging/ ; }, abstract = {OBJECTIVE: This paper presents magnetic resonance images of the dorsi- and plantar flexor muscles for individual young and older healthy adults. Also included are measurements of the volume, proportion, and longitudinal distribution of contractile and non-contractile tissue. This dataset was previously used to quantify age-related differences in these measures, constrain subject- and muscle-specific estimates of dorsi- and plantar flexor maximal isometric force capability, and quantify the degree to which maximal isometric force capability explains the age-related variance in postural control.

DATA DESCRIPTION: The data include contiguous axial magnetic resonance images of the lower leg for 12 young (21-31 years) and 12 older (66-79 years) healthy adults. The data are in the form of MATLAB binary files with a freely distributable custom MATLAB analysis program that allows image viewing and navigation in two and three dimensions, muscle outlining, tissue segmentation, and cross-sectional area calculation. The latter measurements are contained in a set of companion MATLAB binary files, which are included with the image data files. If desired, the magnetic resonance images could be used to identify other anatomical structures, or the MATLAB programs could be used to analyze other image sets.}, } @article {pmid30572933, year = {2018}, author = {Bedaso, A and Duko, B and Fedlu, R}, title = {Knowledge on HBV vaccine and vaccination status among health care workers of Hawassa University Comprehensive Specialized Hospital, Hawassa, southern Ethiopia: a cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {912}, doi = {10.1186/s13104-018-4023-0}, pmid = {30572933}, issn = {1756-0500}, abstract = {OBJECTIVES: The study was conducted to assess the knowledge on HBV vaccine and vaccination status among health care workers of Hawassa University Comprehensive Specialized Hospital.

RESULT: From the total 258 questionnaire prepared for the study participant, data was collected from 241 participants making the response rate of 93.4%. Regarding socio-demographic characteristics of respondents 98 (40.7%), and 159 (66%) were females and Bachelor of Science graduates respectively. Only 73 (30.3%) respondents reported that they are vaccinated for hepatitis B vaccine. But only 16 (21.9%) received three doses of Hepatitis B vaccine, which was 6.6% of the total health care workers. More than half 146 (60.6%) of the respondents had good knowledge about hepatitis B virus infection and 120 (49.8%) had good knowledge about hepatitis B vaccine. Regarding knowledge about hepatitis B virus infection prevention and control methods, 131 (28.5%) of the respondents have good knowledge.}, } @article {pmid30572932, year = {2018}, author = {Fakir, AMS and Aziz, M and Mubde, MB and Karim, A and Khan, AS and Raisa, R and Alim, LF and Fahmin, M}, title = {Bangladesh Chars Tobacco Assessment Project (CTAP) 2018: a data note.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {914}, doi = {10.1186/s13104-018-4015-0}, pmid = {30572932}, issn = {1756-0500}, support = {TobaccoControl/2018-02//Bangladesh Center for Communication Programs (BCCP)/ ; }, abstract = {OBJECTIVES: The Chars Tobacco Assessment Project 2018 is a holistic survey conducted in the chars (riverine islands) of Gaibandha in Northern Bangladesh, covering 985 households over 24 clusters. The survey was conducted with two objectives: (1) to assess levels of tobacco consumption and evaluate prevailing socio-economic, behavioral and health status of the chars population, and (2) to look at the effectiveness of advocacy campaigns to reduce tobacco consumption through behavioral nudges via randomized controlled trials (RCTs) in rural Bangladesh. The study site was purposively chosen due to its high tobacco consumption rate, and the geographical segregation of the chars aided in reducing spillovers for RCT design.

DATA DESCRIPTION: In addition to detailed information on tobacco (smoking and smokeless) consumption and perception, data was collected on: household composition, housing and plot ownership, consumption, risks and shocks coping, dowry, farm production, loans, savings and lending, labor income, asset holdings, migration and remittance, anthropometry, respiratory diseases, co-morbidities, reproductive history, risk and time preference. Unique to the dataset are carbon monoxide readings for accurate short term smoking measurement and FEV1 and PEF values for identification of long term lung damage. The data is representative only for the chars of Gaibandha.}, } @article {pmid30572929, year = {2018}, author = {Moeinzadeh, H and Bifulco, P and Cesarelli, M and McEwan, AL and O'Loughlin, A and Shugman, IM and Tapson, JC and Thiagalingam, A and Gargiulo, GD}, title = {Minimization of the Wilson's Central Terminal voltage potential via a genetic algorithm.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {915}, doi = {10.1186/s13104-018-4017-y}, pmid = {30572929}, issn = {1756-0500}, support = {UWSPRA//Western Sydney University/ ; }, abstract = {OBJECTIVE: The Wilson Central Terminal (WCT) is an artificially constructed reference for surface electrocardiography, which is assumed to be near zero and steady during the cardiac cycle; namely it is the simple average of the three recorded limbs (right arm, left arm and left leg) composing the Einthoven triangle and considered to be electrically equidistant from the electrical center of the heart. This assumption has been challenged and disproved in 1954 with an experiment designed just to measure and minimize WCT. Minimization was attempted varying in real time the weight resistors connected to the limbs. Unfortunately, the experiment required a very cumbersome setup and showed that WCT amplitude could not be universally minimized, in other words, the weight resistors change for each person. Taking advantage of modern computation techniques as well as of a special ECG device that aside of the standard 12-lead Electrocardiogram (ECG) can measure WCT components, we propose a software minimization (genetic algorithm) method using data recorded from 72 volunteers.

RESULT: We show that while the WCT presents average amplitude relative to lead II of 58.85% (standard deviation of 30.84%), our minimization method yields an amplitude as small as 7.45% of lead II (standard deviation of 9.04%).}, } @article {pmid30572866, year = {2018}, author = {Blanchard, P and Lauzeral, C and Chamaillé-Jammes, S and Brunet, C and Lec'hvien, A and Péron, G and Pontier, D}, title = {Coping with change in predation risk across space and time through complementary behavioral responses.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {60}, doi = {10.1186/s12898-018-0215-7}, pmid = {30572866}, issn = {1472-6785}, support = {279//Institut Polaire Français Paul Emile Victor/ ; }, abstract = {BACKGROUND: Our picture of behavioral management of risk by prey remains fragmentary. This partly stems from a lack of studies jointly analyzing different behavioral responses developed by prey, such as habitat use and fine-scale behavior, although they are expected to complement each other. We took advantage of a simple system on the Kerguelen archipelago, made of a prey species, European rabbit Oryctolagus cuniculus, a predator, feral cat Felis catus, and a mosaic of closed and open foraging patches, allowing reliable assessment of spatio-temporal change in predation risk. We investigated the way such a change triggered individual prey decisions on where, when and how to perform routine activities.

RESULTS: Rabbit presence and behavior were recorded both day and night in patches with similar foraging characteristics, but contrasted in terms of openness. Cats, individually recognizable, were more active at night and in closed patches, in line with their expected higher hunting success in those conditions. Accordingly, rabbits avoided using closed patches at night and increased their vigilance if they did. Both day and night, rabbits increased their use of closed patches as compared to open patches in windy conditions, thereby probably reducing the thermoregulatory costs expected under such harsh environmental conditions.

CONCLUSIONS: Overall, our data map the landscape of fear in this study system and indicate that prey habitat use and vigilance complement each other. Solely focusing on one or the other tactic may lead to erroneous conclusions regarding the way predation risk triggers prey decisions. Finally, future studies should investigate inter-individual variability in the relative use of these different types of complementary behavioral responses to perceived risk, along with the determinants and outcomes of such tactics.}, } @article {pmid30572844, year = {2018}, author = {Li, N and Bao, L and Zhou, T and Yuan, Z and Liu, S and Dunham, R and Li, Y and Wang, K and Xu, X and Jin, Y and Zeng, Q and Gao, S and Fu, Q and Liu, Y and Yang, Y and Li, Q and Meyer, A and Gao, D and Liu, Z}, title = {Genome sequence of walking catfish (Clarias batrachus) provides insights into terrestrial adaptation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {952}, doi = {10.1186/s12864-018-5355-9}, pmid = {30572844}, issn = {1471-2164}, support = {2009-35205-05101, 2012-67015-19410, 2017-67015-26295//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: Walking catfish (Clarias batrachus) is a freshwater fish capable of air-breathing and locomotion on land. It usually inhabits various low-oxygen habitats, burrows inside the mudflat, and sometimes "walks" to search for suitable environments during summer. It has evolved accessory air-breathing organs for respiring air and corresponding mechanisms to survive in such challenging environments. Thereby, it serves as a great model for understanding adaptations to terrestrial life.

RESULTS: Comparative genomics with channel catfish (Ictalurus punctatus) revealed specific adaptations of C. batrachus in DNA repair, enzyme activator activity, and small GTPase regulator activity. Comparative analysis with 11 non-air-breathing fish species suggested adaptive evolution in gene expression and nitrogenous waste metabolic processes. Further, myoglobin, olfactory receptor related to class A G protein-coupled receptor 1, and sulfotransferase 6b1 genes were found to be expanded in the air-breathing walking catfish genome, with 15, 15, and 12 copies, respectively, compared to non-air-breathing fishes that possess only 1-2 copies of these genes. Additionally, we sequenced and compared the transcriptomes of the gill and the air-breathing organ to characterize the mechanism of aerial respiration involved in elastic fiber formation, oxygen binding and transport, angiogenesis, ion homeostasis and acid-base balance. The hemoglobin genes were expressed dramatically higher in the air-breathing organ than in the gill of walking catfish.

CONCLUSIONS: This study provides an important genomic resource for understanding the adaptive mechanisms of walking catfish to terrestrial environments. It is possible that the coupling of enhanced abilities for oxygen storage and oxygen transport through genomic expansion of myoglobin genes and transcriptomic up-regulation of hemoglobin and angiogenesis-related genes are important components of the molecular basis for adaptation of this aquatic species to terrestrial life.}, } @article {pmid30572840, year = {2018}, author = {Wang, S and Yang, C and Zhao, X and Chen, S and Qu, GZ}, title = {Complete chloroplast genome sequence of Betula platyphylla: gene organization, RNA editing, and comparative and phylogenetic analyses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {950}, doi = {10.1186/s12864-018-5346-x}, pmid = {30572840}, issn = {1471-2164}, support = {No. 31770712//National Natural Science Foundation of China/ ; 2572015EA03//Fundamental Research Funds for the Central Universities/ ; }, abstract = {BACKGROUND: Betula platyphylla is a common tree species in northern China that has high economic and medicinal value. Our laboratory has been devoted to genome research on B. platyphylla for approximately 10 years. As primary organelle genomes, the complete genome sequences of chloroplasts are important to study the divergence of species, RNA editing and phylogeny. In this study, we sequenced and analyzed the complete chloroplast (cp) genome sequence of B. platyphylla.

RESULTS: The complete cp genome of B. platyphylla was 160,518 bp in length, which included a pair of inverted repeats (IRs) of 26,056 bp that separated a large single copy (LSC) region of 89,397 bp and a small single copy (SSC) region of 19,009 bp. The annotation contained a total of 129 genes, including 84 protein-coding genes, 37 tRNA genes and 8 rRNA genes. There were 3 genes using alternative initiation codons. Comparative genomics showed that the sequence of the Fagales species cp genome was relatively conserved, but there were still some high variation regions that could be used as molecular markers. The IR expansion event of B. platyphylla resulted in larger cp genomes and rps19 pseudogene formation. The simple sequence repeat (SSR) analysis showed that there were 105 SSRs in the cp genome of B. platyphylla. RNA editing sites recognition indicated that at least 80 RNA editing events occurred in the cp genome. Most of the substitutions were C to U, while a small proportion of them were not. In particular, three editing loci on the rRNA were converted to more than two other bases that had never been reported. For synonymous conversion, most of them increased the relative synonymous codon usage (RSCU) value of the codons. The phylogenetic analysis suggested that B. platyphylla had a closer evolutionary relationship with B. pendula than B. nana.

CONCLUSIONS: In this study, we not only obtained and annotated the complete cp genome sequence of B. platyphylla, but we also identified new RNA editing sites and predicted the phylogenetic relationships among Fagales species. These findings will facilitate genomic, genetic engineering and phylogenetic studies of this important species.}, } @article {pmid30572838, year = {2018}, author = {Thakur, O and Randhawa, GS}, title = {Identification and characterization of SSR, SNP and InDel molecular markers from RNA-Seq data of guar (Cyamopsis tetragonoloba, L. Taub.) roots.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {951}, doi = {10.1186/s12864-018-5205-9}, pmid = {30572838}, issn = {1471-2164}, abstract = {BACKGROUND: Guar [Cyamopsis tetragonoloba, L. Taub.] is an important industrial crop because of the commercial applications of the galactomannan gum contained in its seeds. Plant breeding programmes based on marker-assisted selection require a rich resource of molecular markers. As limited numbers of such markers are available for guar, molecular breeding programmes have not been undertaken for the genetic improvement of this important crop. Hence, the present work was done to enrich the molecular markers resource of guar by identifying high quality SSR, SNP and InDel markers from the RNA-Seq data of the roots of two guar varieties.

RESULTS: We carried out RNA-Seq analysis of the roots of two guar varieties, namely, RGC-1066 and M-83. A total of 102,479 unigenes with an average length of 1016 bp were assembled from about 30 million high quality pair-end reads generated by an Illumina HiSeq 2500 platform. The assembled unigenes had 86.55% complete and 97.71% partially conserved eukaryotic genes (CEGs). The functional annotation of assembled unigenes using BLASTX against six databases showed that the guar unigenes were most similar to Glycine max. We could assign GO terms to 45,200 unigenes using the UniProt database. The screening of 102,479 unigenes with MISA and SAMtools version 1.4 softwares resulted in the identification of 25,040 high-confidence molecular markers which consisted of 18,792 SSRs, 5999 SNPs and 249 InDels. These markers tagged most of the genes involved in root development, stress tolerance and other general metabolic activities. Each of the 25,040 molecular markers was characterized, particularly with respect to its position in the unigene. For 71% of the molecular markers, we could determine the names, products and functions of the unigenes. About 80% of the markers, from a random sample of molecular markers, showed PCR amplification.

CONCLUSIONS: We have identified and characterized 25,040 high confidence SSR, SNP and InDel molecular markers in guar. It is expected that these markers will be useful in molecular breeding programmes and will also be helpful in studying molecular mechanisms of root development, stress tolerance and gum synthesis in guar.}, } @article {pmid30572836, year = {2018}, author = {Cherifi, T and Carrillo, C and Lambert, D and Miniaï, I and Quessy, S and Larivière-Gauthier, G and Blais, B and Fravalo, P}, title = {Genomic characterization of Listeria monocytogenes isolates reveals that their persistence in a pig slaughterhouse is linked to the presence of benzalkonium chloride resistance genes.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {220}, doi = {10.1186/s12866-018-1363-9}, pmid = {30572836}, issn = {1471-2180}, support = {Food 1020 and 1231//Canadian Food Inspection Agency/ ; RDCPJ 520873-17//Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {BACKGROUND: The aim of this study was to characterize the genomes of 30 Listeria monocytogenes isolates collected at a pig slaughterhouse to determine the molecular basis for their persistence.

RESULTS: Comparison of the 30 L. monocytogenes genomes showed that successive isolates (i.e., persistent types) recovered from thew sampling site could be linked on the basis of single nucleotide variants confined to prophage regions. In addition, our study revealed the presence among these strains of the bcrABC cassette which is known to produce efflux pump-mediated benzalkonium chloride resistance, and which may account for the persistence of these isolates in the slaughterhouse environment. The presence of the bcrABC cassette was confirmed by WGS and PCR and the resistance phenotype was determined by measuring minimum inhibitory concentrations. Furthermore, the BC-resistant strains were found to produce lower amounts of biofilm in the presence of sublethal concentrations of BC.

CONCLUSIONS: High resolution SNP-based typing and determination of the bcrABC cassette may provide a means of distinguishing between resident and sporadic L. monocytogenes isolates, and this in turn will support better management of this pathogen in the food industry.}, } @article {pmid30572834, year = {2018}, author = {Yang, G and Gao, X and Ma, K and Li, D and Jia, C and Zhai, M and Xu, Z}, title = {The walnut transcription factor JrGRAS2 contributes to high temperature stress tolerance involving in Dof transcriptional regulation and HSP protein expression.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {367}, doi = {10.1186/s12870-018-1568-y}, pmid = {30572834}, issn = {1471-2229}, support = {2452016057, 2452015171//Central University Basic Research Funds Project of China/ ; 2452015295//Inaugurating Program of Northwest A & F University for Doctoral Staff/ ; 2018JQ3066//Natural Science Basic Research Project of Shaanxi Province/ ; 31700332//National Natural Science Foundation of China/ ; 31800510//National Natural Science Foundation of China/ ; 2017T100782//Special Financial Grant from the China Postdoctoral Science Foundation/ ; }, abstract = {BACKGROUND: GRAS transcription factor (TF) family is unique and numerous in higher plants with diverse functions that involving in plant growth and development processes, such as gibberellin (GA) signal transduction, root development, root nodule formation, and mycorrhiza formation. Walnut tree is exposed to various environmental stimulus that causing concern about its resistance mechanism. In order to understand the molecular mechanism of walnut to adversity response, a GRAS TF (JrGRAS2) was cloned and characterized from Juglans regia in this study.

RESULTS: A 1500 bp promoter fragment of JrGRAS2 was identified from the genome of J. regia, in which the cis-elements were screened. This JrGRAS2 promoter displayed expression activity that was enhanced significantly by high temperature (HT) stress. Yeast one-hybrid assay, transient expression and chromatin immunoprecipitation (Chip)-PCR analysis revealed that JrDof3 could specifically bind to the DOFCOREZM motif and share similar expression patterns with JrGRAS2 under HT stress. The transcription of JrGRAS2 was induced by HT stress and up-regulated to 6.73-~11.96-fold in the leaf and 2.53-~4.50-fold in the root to control, respectively. JrGRAS2 was overexpressed in Arabidopsis, three lines with much high expression level of JrGRAS2 (S3, S7, and S8) were selected for HT stress tolerance analysis. Compared to the wild type (WT) Arabidopsis, S3, S7, and S8 exhibited enhanced seed germination rate, fresh weight accumulation, and activities of catalase (CAT), peroxidase (POD), superoxide dismutase (SOD) and glutathione-S-transferase (GST) under HT stress. In contrast, the Evans blue staining, electrolyte leakage (EL) rates, hydrogen dioxide (H2O2) and malondialdehyde (MDA) content of transgenic seedlings were all lower than those of WT exposed to HT stress. Furthermore, the expression of heat shock proteins (HSPs) in S3, S7, and S8 was significant higher than those in WT plants. The similar results were obtained in JrGRAS2 transient overexpression walnut lines under normal and HT stress conditions.

CONCLUSIONS: Our results suggested that JrDof3 TF contributes to improve the HT stress response of JrGRAS2, which could effectively control the expression of HSPs to enhance HT stress tolerance. JrGRAS2 is an useful candidate gene for heat response in plant molecular breeding.}, } @article {pmid30572831, year = {2018}, author = {Morita, M and Ugwu, SI and Kohda, M}, title = {Variations in the breeding behavior of cichlids and the evolution of the multi-functional seminal plasma protein, seminal plasma glycoprotein 120.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {197}, doi = {10.1186/s12862-018-1292-0}, pmid = {30572831}, issn = {1471-2148}, abstract = {BACKGROUND: Seminal plasma proteins are associated with successful fertilization. However, their evolutionary correlation with fertilization mechanisms remains unclear. Cichlids from Lake Tanganyika show a variety-rich spawning behavior that is associated with the transfer of the sperm to the egg for fertilization. One of these behaviors, called "oral fertilization," emerged during their speciation. In oral fertilization, females nuzzle the milt from male genitalia and pick up the released eggs in their mouths, which are then fertilized inside the oral cavity. Thus, the success of the fertilization is dependent on the retention of sperm in the oral cavity during spawning. Sperm aggregation and immobilization in viscous seminal plasma may help retain the sperm inside the oral cavity, which ultimately determines the success of the fertilization. Seminal plasma glycoprotein 120 (SPP120) is one of the major seminal plasma proteins present in cichlids. SPP120 has been implicated to immobilize sperm and increase the milt viscosity. However, the functional linkage between oral fertilization and seminal plasma proteins has not been investigated.

RESULTS: During trials of simulated oral fertilization, it was observed that milt viscosity contributed to fertilization success by facilitating longer retention of the milt inside the mouth during spawning. Glycosylation of SPP120 was associated with high milt viscosity. Its glycosylation was specifically present in the milt of cichlid species exhibiting oral fertilization. Moreover, recombinant SPP120 from several the oral fertilization species strongly immobilized/aggregated sperm. Therefore, the functions of SPP120 (immobilization/aggregation and its glycosylation) may contribute to success of oral fertilization, and these functions of SPP120 are more prominent in oral fertilization species. In addition, comparative phylogenetic analyses showed a positive evolutionary correlation between SPP120 function and oral fertilization. Hence, these evolutions may have occurred to keep up with the transition in the mode of fertilization. In addition, rapid evolution in the molecular sequence might be associated with functional modifications of SPP120.

CONCLUSION: These results suggest that SPP120 might be associated with oral fertilization. In other words, reproductive traits that define the interaction between sperms and eggs could be the evolutionary selective force that cause the rapid functional modification of the fertilization-related reproductive protein, SPP120.}, } @article {pmid30572829, year = {2018}, author = {Stevens, JR and Herrick, JS and Wolff, RK and Slattery, ML}, title = {Power in pairs: assessing the statistical value of paired samples in tests for differential expression.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {953}, doi = {10.1186/s12864-018-5236-2}, pmid = {30572829}, issn = {1471-2164}, support = {CA16383//National Cancer Institute/ ; CA48998//National Cancer Institute/ ; }, abstract = {BACKGROUND: When genomics researchers design a high-throughput study to test for differential expression, some biological systems and research questions provide opportunities to use paired samples from subjects, and researchers can plan for a certain proportion of subjects to have paired samples. We consider the effect of this paired samples proportion on the statistical power of the study, using characteristics of both count (RNA-Seq) and continuous (microarray) expression data from a colorectal cancer study.

RESULTS: We demonstrate that a higher proportion of subjects with paired samples yields higher statistical power, for various total numbers of samples, and for various strengths of subject-level confounding factors. In the design scenarios considered, the statistical power in a fully-paired design is substantially (and in many cases several times) greater than in an unpaired design.

CONCLUSIONS: For the many biological systems and research questions where paired samples are feasible and relevant, substantial statistical power gains can be achieved at the study design stage when genomics researchers plan on using paired samples from the largest possible proportion of subjects. Any cost savings in a study design with unpaired samples are likely accompanied by underpowered and possibly biased results.}, } @article {pmid30572828, year = {2018}, author = {Gaspar, JM}, title = {NGmerge: merging paired-end reads via novel empirically-derived models of sequencing errors.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {536}, doi = {10.1186/s12859-018-2579-2}, pmid = {30572828}, issn = {1471-2105}, mesh = {High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Advances in Illumina DNA sequencing technology have produced longer paired-end reads that increasingly have sequence overlaps. These reads can be merged into a single read that spans the full length of the original DNA fragment, allowing for error correction and accurate determination of read coverage. Extant merging programs utilize simplistic or unverified models for the selection of bases and quality scores for the overlapping region of merged reads.

RESULTS: We first examined the baseline quality score - error rate relationship using sequence reads derived from PhiX. In contrast to numerous published reports, we found that the quality scores produced by Illumina were not substantially inflated above the theoretical values, once the reference genome was corrected for unreported sequence variants. The PhiX reads were then used to create empirical models of sequencing errors in overlapping regions of paired-end reads, and these models were incorporated into a novel merging program, NGmerge. We demonstrate that NGmerge corrects errors and ambiguous bases better than other merging programs, and that it assigns quality scores for merged bases that accurately reflect the error rates. Our results also show that, contrary to published analyses, the sequencing errors of paired-end reads are not independent.

CONCLUSIONS: We provide a free and open-source program, NGmerge, that performs better than existing read merging programs. NGmerge is available on GitHub (https://github.com/harvardinformatics/NGmerge) under the MIT License; it is written in C and supported on Linux.}, } @article {pmid30572824, year = {2018}, author = {Zhang, W and Gao, X and Zhang, Y and Zhao, Y and Zhang, J and Jia, Y and Zhu, B and Xu, L and Zhang, L and Gao, H and Li, J and Chen, Y}, title = {Genome-wide assessment of genetic diversity and population structure insights into admixture and introgression in Chinese indigenous cattle.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {114}, doi = {10.1186/s12863-018-0705-9}, pmid = {30572824}, issn = {1471-2156}, support = {31402039//National Natural Science Foundation of China/ ; CAAS-XTCX2016010, CAAS-ZDXT2018006, ASTIPIAS03//Chinese Academy of Agricultural Sciences of Technology Innovation Project/ ; CARS-37//National Beef Cattle Industrial Technology System/ ; }, abstract = {BACKGROUND: China exhibits a great diversity of ecosystems and abundant cattle resources, with nearly 30 million cattle from 53 indigenous breeds reared in specific geographic regions. To explore the genetic diversity and population structure of Chinese indigenous cattle, a population genetic analysis at both the individual and population levels was conducted and the admixture analysis was performed. We genotyped 572 samples from 20 Chinese indigenous cattle breeds using GeneSeek Genomic Profiler Bovine LD (GGP-LD, 30 K) and downloaded the published data of 77 samples from 4 worldwide commercial breeds genotyped with Illumina BovineSNP50 Beadchip (SNP50, 50 K).

RESULTS: In principal component analysis (PCA) and neighbour-joining (NJ) tree analysis, samples of the same breeds were grouped together, leading to clear separation from other breeds. And Chinese indigenous cattle were clustered into two groups of southern and northern breeds, originated from Asian Bos indicus lineage and Eurasian Bos taurus lineage, respectively. In STRUCTURE K = 2, a clear transition occurred from the northern breeds to the southern breeds. Additionally, the northern breeds contained a smaller Eurasian taurine (62.5%) descent proportion than that reported previously (more than 90%). In STRUCTURE K = 3, a distinct descent was detected in the southern Chinese breeds, which could reflect a long-term selection history of Chinese indigenous cattle. The results from TreeMix and f3 statistic provided the evidence of an admixture history between southern breeds and northern breeds.

CONCLUSIONS: Consistent with the observed geographical distributions, Chinese indigenous cattle were divided into two genetic clusters, northern indigenous cattle and southern indigenous cattle. Three improved breeds in the northern area also exhibited northern indigenous ancestry. We found that the breeds distributed in the northern China showed more southern lineage introgression than previously reported. Central-located populations appeared to the admixture between southern and northern lineages, and introgression events from European cattle were observed in Luxi Cattle, Qinchuan Cattle and Jinnan Cattle. The study revealed the population structures and levels of admixture pattern among Chinese indigenous cattle, shedding light on the origin and evolutionary history of these breeds.}, } @article {pmid30572820, year = {2018}, author = {Xu, B and Li, K and Zheng, W and Liu, X and Zhang, Y and Zhao, Z and He, Z}, title = {Protein complexes identification based on go attributed network embedding.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {535}, doi = {10.1186/s12859-018-2555-x}, pmid = {30572820}, issn = {1471-2105}, support = {No.61502071//National Natural Science Foundation of China/ ; No.61572094//National Natural Science Foundation of China/ ; No. DUT18RC(3)004//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Humans ; Protein Interaction Mapping/*methods ; Proteins/*metabolism ; Proteomics/*methods ; }, abstract = {BACKGROUND: Identifying protein complexes from protein-protein interaction (PPI) network is one of the most important tasks in proteomics. Existing computational methods try to incorporate a variety of biological evidences to enhance the quality of predicted complexes. However, it is still a challenge to integrate different types of biological information into the complexes discovery process under a unified framework. Recently, attributed network embedding methods have be proved to be remarkably effective in generating vector representations for nodes in the network. In the transformed vector space, both the topological proximity and node attributed affinity between different nodes are preserved. Therefore, such attributed network embedding methods provide us a unified framework to integrate various biological evidences into the protein complexes identification process.

RESULTS: In this article, we propose a new method called GANE to predict protein complexes based on Gene Ontology (GO) attributed network embedding. Firstly, it learns the vector representation for each protein from a GO attributed PPI network. Based on the pair-wise vector representation similarity, a weighted adjacency matrix is constructed. Secondly, it uses the clique mining method to generate candidate cores. Consequently, seed cores are obtained by ranking candidate cores based on their densities on the weighted adjacency matrix and removing redundant cores. For each seed core, its attachments are the proteins with correlation score that is larger than a given threshold. The combination of a seed core and its attachment proteins is reported as a predicted protein complex by the GANE algorithm. For performance evaluation, we compared GANE with six protein complex identification methods on five yeast PPI networks. Experimental results showes that GANE performs better than the competing algorithms in terms of different evaluation metrics.

CONCLUSIONS: GANE provides a framework that integrate many valuable and different biological information into the task of protein complex identification. The protein vector representation learned from our attributed PPI network can also be used in other tasks, such as PPI prediction and disease gene prediction.}, } @article {pmid30572819, year = {2018}, author = {Dini, P and Daels, P and Loux, SC and Esteller-Vico, A and Carossino, M and Scoggin, KE and Ball, BA}, title = {Kinetics of the chromosome 14 microRNA cluster ortholog and its potential role during placental development in the pregnant mare.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {954}, doi = {10.1186/s12864-018-5341-2}, pmid = {30572819}, issn = {1471-2164}, abstract = {BACKGROUND: The human chromosome 14 microRNA cluster (C14MC) is a conserved microRNA (miRNA) cluster across eutherian mammals, reported to play an important role in placental development. However, the expression kinetics and function of this cluster in the mammalian placenta are poorly understood. Here, we evaluated the expression kinetics of the equine C24MC, ortholog to the human C14MC, in the chorioallantoic membrane during the course of gestation.

RESULTS: We demonstrated that C24MC-associated miRNAs presented a higher expression level during early stages of pregnancy, followed by a decline later in gestation. Evaluation of one member of C24MC (miR-409-3p) by in situ hybridization demonstrated that its cellular localization predominantly involved the chorion and allantoic epithelium and vascular endothelium. Additionally, expression of predicted target transcripts for C24MC-associated miRNAs was evaluated by RNA sequencing. Expression analysis of a subset of predicted mRNA targets showed a negative correlation with C24MC-associated miRNAs expression levels during gestation, suggesting the reciprocal control of these target transcripts by this miRNA cluster. Predicted functional analysis of these target mRNAs indicated enrichment of biological pathways related to embryonic development, endothelial cell migration and angiogenesis. Expression patterns of selected target mRNAs involved in angiogenesis were confirmed by RT-qPCR.

CONCLUSION: This is the first report evaluating C24MC kinetics during pregnancy. The findings presented herein suggest that the C24MC may modulate angiogenic transcriptional profiles during placental development in the horse.}, } @article {pmid30572817, year = {2018}, author = {Bonte, C and Makri, E and Ardeshirdavani, A and Simm, J and Moreau, Y and Vercauteren, F}, title = {Towards practical privacy-preserving genome-wide association study.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {537}, doi = {10.1186/s12859-018-2541-3}, pmid = {30572817}, issn = {1471-2105}, mesh = {Genome-Wide Association Study/*methods ; Genomics/*methods ; Humans ; }, abstract = {BACKGROUND: The deployment of Genome-wide association studies (GWASs) requires genomic information of a large population to produce reliable results. This raises significant privacy concerns, making people hesitate to contribute their genetic information to such studies.

RESULTS: We propose two provably secure solutions to address this challenge: (1) a somewhat homomorphic encryption (HE) approach, and (2) a secure multiparty computation (MPC) approach. Unlike previous work, our approach does not rely on adding noise to the input data, nor does it reveal any information about the patients. Our protocols aim to prevent data breaches by calculating the χ2 statistic in a privacy-preserving manner, without revealing any information other than whether the statistic is significant or not. Specifically, our protocols compute the χ2 statistic, but only return a yes/no answer, indicating significance. By not revealing the statistic value itself but only the significance, our approach thwarts attacks exploiting statistic values. We significantly increased the efficiency of our HE protocols by introducing a new masking technique to perform the secure comparison that is necessary for determining significance.

CONCLUSIONS: We show that full-scale privacy-preserving GWAS is practical, as long as the statistics can be computed by low degree polynomials. Our implementations demonstrated that both approaches are efficient. The secure multiparty computation technique completes its execution in approximately 2 ms for data contributed by one million subjects.}, } @article {pmid30572020, year = {2018}, author = {Uribe, JE and Irisarri, I and Templado, J and Zardoya, R}, title = {New patellogastropod mitogenomes help counteracting long-branch attraction in the deep phylogeny of gastropod mollusks.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {12-23}, doi = {10.1016/j.ympev.2018.12.019}, pmid = {30572020}, issn = {1095-9513}, abstract = {Long-branch attraction (LBA) is a well-known artifact in phylogenetic reconstruction. Sparse taxon sampling and extreme heterogeneity of evolutionary rates among lineages generate propitious situations for LBA, even defying probabilistic methods of phylogenetic inference. A clear example illustrating LBA challenges is the difficulty of reconstructing the deep gastropod phylogeny, particularly using mitochondrial (mt) genomes. Previous studies consistently obtained unorthodox phylogenetic relationships due to the LBA between the mitogenomes of patellogastropods (true limpets, represented only by Lottia digitalis), heterobranchs, and outgroup taxa. Here, we use the reconstruction of the gastropod mitogenomic phylogeny as a case exercise to test the effect of key methodological approaches proposed to counteract LBA, including the selection of slow-evolving representatives, the use of different outgroups, the application of site-heterogeneous evolutionary models, and the removal of fast-evolving sites. In this regard, we sequenced three new patellogastropod mt genomes, which displayed shorter branches than the one of Lottia as well as gene organizations more similar to that of the hypothetical gastropod ancestor. Phylogenetic analyses incorporating the mt genomes of Patella ferruginea, Patella vulgata, and Cellana radiata allowed eliminating the artificial clustering of Patellogastropoda and Heterobranchia that had prevailed in previous studies. Furthermore, the use of site-heterogeneous models with certain combinations of lineages within the outgroup allowed eliminating also the LBA between Heterobranchia and the outgroup, and recovering Apogastropoda (i.e., Caenogastropoda + Heterobranchia). Hence, for the first time, we were able to obtain a mitogenomic phylogeny of gastropods that is congruent with both morphological and nuclear datasets.}, } @article {pmid30570482, year = {2018}, author = {On, YG and Oh, JS and Roh, DH}, title = {Zhongshania marina sp. nov., isolated from deep-sea water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003195}, pmid = {30570482}, issn = {1466-5034}, abstract = {A Gram-stain-negative, aerobic, catalase-positive, oxidase-positive, motile by a single polar flagellum, rod-shaped strain, designated DSW25-10T, was isolated from the deep-sea water of the East Sea, Republic of Korea. Strain DSW25-10Tgrew at 4-35 °C (optimum, 20-35 °C), at pH 5.5-9.0 (optimum, pH 7.0) and in the presence of 0-6.0 % NaCl (optimum, 0.5-2 %), and could assimilate valerate, but not assimilate d-mannitol and 3-hydroxy-butyrate. Comparative 16S rRNA gene sequence analysis showed that strain DSW25-10T belongs to the genus Zhongshania in the family Spongiibacteraceae and is most closely related to Zhongshania guokunii ZS6-22T, Zhongshaniaborealis CL-AS9T, Zhongshaniaaliphaticivorans SM-2T and Zhongshaniaantarctica ZS5-23T with a similarities of 97.1, 97.0, 96.7 and 96.6 %, respectively. The G+C content of genomic DNA was 49.1 mol% and the major respiratory quinone was ubiquinone-8. Phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol were identified as the major cellular polar lipids. The predominant cellular fatty acids in strain DSW25-10T were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0 and C17 : 1ω8c. The DNA-DNA relatedness values between strain DSW25-10T and related strains were clearly lower than 70 %. On the basis of evidence from a polyphasic analysis, strain DSW25-10T is proposed to represent a novel species, Zhongshania marina sp. nov. The type strain is DSW25-10T (=KCCM 43273T=JCM 17372T).}, } @article {pmid30570480, year = {2018}, author = {Oren, A and Chuvochina, M and Ventura, S}, title = {Formation of compound generic names based on personal names: a proposal for emendation of Appendix 9 of the International Code of Nomenclature of Prokaryotes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003192}, pmid = {30570480}, issn = {1466-5034}, abstract = {Appendix 9, the orthography appendix of the International Code of Nomenclature of Prokaryotes, provides guidelines for the correct formation of generic names and specific epithets to honour famous microbiologists and other persons connected with natural science. However, no guidelines are given for the correct formation of compound generic names in which the first word element is derived from a personal name. Currently there are 16 such names validly published under the Rules of the Code, but the ways they were formed are inconsistent. We therefore propose an emendation of Appendix 9 to provide uniform guidelines for the formation of such names in the future.}, } @article {pmid30570478, year = {2018}, author = {Qiao, Z and Cao, M and Wang, D and Liao, S and Wang, G}, title = {Sphingosinicella humi sp. nov., isolated from arsenic-contaminated farmland soil and emended description of the genus Sphingosinicella.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003186}, pmid = {30570478}, issn = {1466-5034}, abstract = {A Gram-stain-negative, strictly aerobic bacterium, designated strain QZX222T, was isolated from arsenic-contaminated farmland soil. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain QZX222T was clustered with Sphingosinicella vermicomposti YC7378T (97.0 %), Sphingosinicellaxenopeptidilytica 3-2W4T (96.1 %), Sphingosinicella microcystinivorans Y2T (96.0 %) and Sphingosinicella soli KSL-125T (95.9 %). Compared to strain QZX222T, Spingomonas olgophenolica JCM 12082T and Sphingobium boeckii 469T had 16S rRNA gene similarities of 96.2 and 95.9 %, respectively, but they located in other phylogenetic clusters. DNA-DNA hybridization and genomic ANI values between strain QZX222T and Sphingosinicella vermicomposti DSM 21593T (KCTC 22446T) were 34.8 and 75.0 %, respectively. The genome size of strain QZX222T was 3.0 Mb including 2982 predicted genes. The strain had a DNA G+C content of 65.9 mol%. Strain QZX222T had ubiquinone Q-10 as the major respiratory quinone and homospermidine as the major polyamine. The major fatty acids (>10 %) of strain QZX222T were C17 : 1ω6c, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C17 : 1ω8c. The polar lipids were sphingoglycolipid, phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and an unidentified glycolipid. Strain QZX222T could be distinguished from other Sphingosinicella strains based on the results of phylogenetic and genomic analyses, DNA-DNA hybridization, white colour colony, hydrolysis of urea, alkaline phosphatase activity, lack of phosphatidylmonomethylethanolamine, and presence of phosphatidylcholine. Therefore, strain QZX222T represents a novel species of Sphingosinicella, for which the name Sphingosinicellahumi sp. nov. is proposed. The type strain is QZX222T (=KCTC 62519T=CCTCC AB 2018030T).}, } @article {pmid30570477, year = {2018}, author = {Bortniak, VL and Pelletier, DA and Newman, JD}, title = {Chryseobacterium populi sp. nov., isolated from Populus deltoides endosphere.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003140}, pmid = {30570477}, issn = {1466-5034}, abstract = {As part of a study investigating the rhizosphere and endosphere of the Eastern cottonwood tree, Populus deltoides, a number of isolates were subjected to genome sequencing. The genome-derived 16S rRNA gene sequence of strain CF314T was 97.0 % similar to those of the Chryseobacterium daecheongense and Chryseobacterium polytrichastri type strains, but was essentially equidistant from many other Chryseobacterium type strains. Overall genome similarity metrics (average nucleotide identity, digital DNA-DNA hybridization, average amino acid identity) revealed greatest similarity to the Chryseobacteriumdaecheongense, Chryseobacteriumpiperi and Chryseobacteriumsoldanellicola type strains, but were well below the species thresholds. Strain CF314T had a typical fatty acid composition for Chryseobacterium species and produced flexirubin pigments, but not carotenoids. The genome encodes a number of proteins such as a C-type lectin and terpene synthases that are also found in other plant-associated Bacteroidetes. Based on phenotypic and genomic characteristics of the strain, we propose the new species Chryseobacteriumpopuli. The type strain is CF314T=KCTC 62722T=LMG 30786T.}, } @article {pmid30570476, year = {2018}, author = {Meng, XL and Ming, H and Huang, JR and Zhang, LY and Cheng, LJ and Zhao, ZL and Ji, WL and Li, WJ and Nie, GX}, title = {Paracoccus halotolerans sp. nov., isolated from a salt lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003190}, pmid = {30570476}, issn = {1466-5034}, abstract = {A novel Gram-stain-negative, aerobic, non-motile, coccus-shaped bacterium, designated CFH 90064T, was isolated from a salt lake sediment sample collected from Yuncheng city, Shanxi province, PR China. 16S rRNA gene sequence comparisons and phylogenetic analyses showed that the strain belonged to the genus Paracoccus and clustered with Paracoccus zeaxanthinifaciens R-1512T (98.2 % similarity), Paracoccus homiensis DD-R11T (97.6 % similarity) and Paracoccus fistulariae 22-5T (96.5 % similarity), respectively. Growth of strain CFH 90064T was observed at 10-37 °C, pH 6.0-9.0 and with NaCl concentrations of up to 6.0 % (w/v). Strain CFH 90064T contained Q-10 as the only isoprenoid quinone, and the major fatty acid was C18 : 1ω7c. Polar lipids of strain CFH 90064T comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified glycolipid, an unidentified aminolipid and an unidentified phospholipid. The genome of strain CFH 90008T was 3.75 Mbp with a DNA G+C content of 65.1 %. Based on the phylogenetic analyses, low average nucleotide identity results, chemotaxonomic characteristics and differential physiological properties, strain CFH 90064T could not be classified into any recognized species of the genus Paracoccus, suggesting that this strain represents a novel species, for which the name Paracoccushalotolerans sp. nov. is proposed. The type strain is CFH 90064T (=CCTCC AB 2016131T=DSM 103234T).}, } @article {pmid30569657, year = {2018}, author = {Wagner, GP}, title = {The first decades of developmental evolution and the Journal of Experimental Zoology.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {8}, pages = {395}, doi = {10.1002/jez.b.22839}, pmid = {30569657}, issn = {1552-5015}, } @article {pmid30569322, year = {2018}, author = {Yang, B and Ye, C and Yan, B and He, X and Xing, K}, title = {Assessing the Influence of Dietary History on Gut Microbiota.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1616-8}, pmid = {30569322}, issn = {1432-0991}, support = {2017A030313121//Natural Science Foundation of Guangdong Province/ ; }, abstract = {Diet is known to play a major role in determining the composition and function of the gut microbiota. Previous studies have often focused on the immediate effects of dietary intervention. How dietary history prior to a given dietary intervention influences the gut microbiota is, however, not well understood. To assess the influence of dietary history, in this study, mice with different dietary histories were subjected to the same dietary interventions, and the gut microbial communities of these mice were characterized by 16S rDNA sequencing. We found that dietary history played a long-lasting role in the composition of the gut microbiota when the dietary switch was moderate. In sharp contrast, such effects nearly vanished when the diet was switched to certain extreme dietary conditions. Interestingly, the abundance of Akkermansia, a bacterial genus associated with loss of body weight, was elevated dramatically in mice subjected to a diet composed exclusively of meat. Our results revealed a more complex picture of the influence of dietary history on gut microbiota than anticipated.}, } @article {pmid30568305, year = {2019}, author = {Keskin, DB and Anandappa, AJ and Sun, J and Tirosh, I and Mathewson, ND and Li, S and Oliveira, G and Giobbie-Hurder, A and Felt, K and Gjini, E and Shukla, SA and Hu, Z and Li, L and Le, PM and Allesøe, RL and Richman, AR and Kowalczyk, MS and Abdelrahman, S and Geduldig, JE and Charbonneau, S and Pelton, K and Iorgulescu, JB and Elagina, L and Zhang, W and Olive, O and McCluskey, C and Olsen, LR and Stevens, J and Lane, WJ and Salazar, AM and Daley, H and Wen, PY and Chiocca, EA and Harden, M and Lennon, NJ and Gabriel, S and Getz, G and Lander, ES and Regev, A and Ritz, J and Neuberg, D and Rodig, SJ and Ligon, KL and Suvà, ML and Wucherpfennig, KW and Hacohen, N and Fritsch, EF and Livak, KJ and Ott, PA and Wu, CJ and Reardon, DA}, title = {Neoantigen vaccine generates intratumoral T cell responses in phase Ib glioblastoma trial.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {234-239}, doi = {10.1038/s41586-018-0792-9}, pmid = {30568305}, issn = {1476-4687}, abstract = {Neoantigens, which are derived from tumour-specific protein-coding mutations, are exempt from central tolerance, can generate robust immune responses1,2 and can function as bona fide antigens that facilitate tumour rejection3. Here we demonstrate that a strategy that uses multi-epitope, personalized neoantigen vaccination, which has previously been tested in patients with high-risk melanoma4-6, is feasible for tumours such as glioblastoma, which typically have a relatively low mutation load1,7 and an immunologically 'cold' tumour microenvironment8. We used personalized neoantigen-targeting vaccines to immunize patients newly diagnosed with glioblastoma following surgical resection and conventional radiotherapy in a phase I/Ib study. Patients who did not receive dexamethasone-a highly potent corticosteroid that is frequently prescribed to treat cerebral oedema in patients with glioblastoma-generated circulating polyfunctional neoantigen-specific CD4+ and CD8+ T cell responses that were enriched in a memory phenotype and showed an increase in the number of tumour-infiltrating T cells. Using single-cell T cell receptor analysis, we provide evidence that neoantigen-specific T cells from the peripheral blood can migrate into an intracranial glioblastoma tumour. Neoantigen-targeting vaccines thus have the potential to favourably alter the immune milieu of glioblastoma.}, } @article {pmid30568304, year = {2019}, author = {Zhang, RK and Chen, K and Huang, X and Wohlschlager, L and Renata, H and Arnold, FH}, title = {Enzymatic assembly of carbon-carbon bonds via iron-catalysed sp3 C-H functionalization.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {67-72}, doi = {10.1038/s41586-018-0808-5}, pmid = {30568304}, issn = {1476-4687}, support = {F32 GM125231/GM/NIGMS NIH HHS/United States ; }, abstract = {Although abundant in organic molecules, carbon-hydrogen (C-H) bonds are typically considered unreactive and unavailable for chemical manipulation. Recent advances in C-H functionalization technology have begun to transform this logic, while emphasizing the importance of and challenges associated with selective alkylation at a sp3 carbon1,2. Here we describe iron-based catalysts for the enantio-, regio- and chemoselective intermolecular alkylation of sp3 C-H bonds through carbene C-H insertion. The catalysts, derived from a cytochrome P450 enzyme in which the native cysteine axial ligand has been substituted for serine (cytochrome P411), are fully genetically encoded and produced in bacteria, where they can be tuned by directed evolution for activity and selectivity. That these proteins activate iron, the most abundant transition metal, to perform this chemistry provides a desirable alternative to noble-metal catalysts, which have dominated the field of C-H functionalization1,2. The laboratory-evolved enzymes functionalize diverse substrates containing benzylic, allylic or α-amino C-H bonds with high turnover and excellent selectivity. Furthermore, they have enabled the development of concise routes to several natural products. The use of the native iron-haem cofactor of these enzymes to mediate sp3 C-H alkylation suggests that diverse haem proteins could serve as potential catalysts for this abiological transformation, and will facilitate the development of new enzymatic C-H functionalization reactions for applications in chemistry and synthetic biology.}, } @article {pmid30568303, year = {2019}, author = {Hilf, N and Kuttruff-Coqui, S and Frenzel, K and Bukur, V and Stevanović, S and Gouttefangeas, C and Platten, M and Tabatabai, G and Dutoit, V and van der Burg, SH and Thor Straten, P and Martínez-Ricarte, F and Ponsati, B and Okada, H and Lassen, U and Admon, A and Ottensmeier, CH and Ulges, A and Kreiter, S and von Deimling, A and Skardelly, M and Migliorini, D and Kroep, JR and Idorn, M and Rodon, J and Piró, J and Poulsen, HS and Shraibman, B and McCann, K and Mendrzyk, R and Löwer, M and Stieglbauer, M and Britten, CM and Capper, D and Welters, MJP and Sahuquillo, J and Kiesel, K and Derhovanessian, E and Rusch, E and Bunse, L and Song, C and Heesch, S and Wagner, C and Kemmer-Brück, A and Ludwig, J and Castle, JC and Schoor, O and Tadmor, AD and Green, E and Fritsche, J and Meyer, M and Pawlowski, N and Dorner, S and Hoffgaard, F and Rössler, B and Maurer, D and Weinschenk, T and Reinhardt, C and Huber, C and Rammensee, HG and Singh-Jasuja, H and Sahin, U and Dietrich, PY and Wick, W}, title = {Actively personalized vaccination trial for newly diagnosed glioblastoma.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {240-245}, doi = {10.1038/s41586-018-0810-y}, pmid = {30568303}, issn = {1476-4687}, abstract = {Patients with glioblastoma currently do not sufficiently benefit from recent breakthroughs in cancer treatment that use checkpoint inhibitors1,2. For treatments using checkpoint inhibitors to be successful, a high mutational load and responses to neoepitopes are thought to be essential3. There is limited intratumoural infiltration of immune cells4 in glioblastoma and these tumours contain only 30-50 non-synonymous mutations5. Exploitation of the full repertoire of tumour antigens-that is, both unmutated antigens and neoepitopes-may offer more effective immunotherapies, especially for tumours with a low mutational load. Here, in the phase I trial GAPVAC-101 of the Glioma Actively Personalized Vaccine Consortium (GAPVAC), we integrated highly individualized vaccinations with both types of tumour antigens into standard care to optimally exploit the limited target space for patients with newly diagnosed glioblastoma. Fifteen patients with glioblastomas positive for human leukocyte antigen (HLA)-A*02:01 or HLA-A*24:02 were treated with a vaccine (APVAC1) derived from a premanufactured library of unmutated antigens followed by treatment with APVAC2, which preferentially targeted neoepitopes. Personalization was based on mutations and analyses of the transcriptomes and immunopeptidomes of the individual tumours. The GAPVAC approach was feasible and vaccines that had poly-ICLC (polyriboinosinic-polyribocytidylic acid-poly-L-lysine carboxymethylcellulose) and granulocyte-macrophage colony-stimulating factor as adjuvants displayed favourable safety and strong immunogenicity. Unmutated APVAC1 antigens elicited sustained responses of central memory CD8+ T cells. APVAC2 induced predominantly CD4+ T cell responses of T helper 1 type against predicted neoepitopes.}, } @article {pmid30568302, year = {2019}, author = {Chen, Y and Ikeda, K and Yoneshiro, T and Scaramozza, A and Tajima, K and Wang, Q and Kim, K and Shinoda, K and Sponton, CH and Brown, Z and Brack, A and Kajimura, S}, title = {Thermal stress induces glycolytic beige fat formation via a myogenic state.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {180-185}, doi = {10.1038/s41586-018-0801-z}, pmid = {30568302}, issn = {1476-4687}, support = {R56 AR060868/AR/NIAMS NIH HHS/United States ; R01 AR061002/AR/NIAMS NIH HHS/United States ; R01 DK097441/DK/NIDDK NIH HHS/United States ; R01 AR060868/AR/NIAMS NIH HHS/United States ; R01 DK108822/DK/NIDDK NIH HHS/United States ; R01 DK112268/DK/NIDDK NIH HHS/United States ; }, abstract = {Environmental cues profoundly affect cellular plasticity in multicellular organisms. For instance, exercise promotes a glycolytic-to-oxidative fibre-type switch in skeletal muscle, and cold acclimation induces beige adipocyte biogenesis in adipose tissue. However, the molecular mechanisms by which physiological or pathological cues evoke developmental plasticity remain incompletely understood. Here we report a type of beige adipocyte that has a critical role in chronic cold adaptation in the absence of β-adrenergic receptor signalling. This beige fat is distinct from conventional beige fat with respect to developmental origin and regulation, and displays enhanced glucose oxidation. We therefore refer to it as glycolytic beige fat. Mechanistically, we identify GA-binding protein α as a regulator of glycolytic beige adipocyte differentiation through a myogenic intermediate. Our study reveals a non-canonical adaptive mechanism by which thermal stress induces progenitor cell plasticity and recruits a distinct form of thermogenic cell that is required for energy homeostasis and survival.}, } @article {pmid30568301, year = {2019}, author = {Chen, Z and Boyken, SE and Jia, M and Busch, F and Flores-Solis, D and Bick, MJ and Lu, P and VanAernum, ZL and Sahasrabuddhe, A and Langan, RA and Bermeo, S and Brunette, TJ and Mulligan, VK and Carter, LP and DiMaio, F and Sgourakis, NG and Wysocki, VH and Baker, D}, title = {Programmable design of orthogonal protein heterodimers.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {106-111}, doi = {10.1038/s41586-018-0802-y}, pmid = {30568301}, issn = {1476-4687}, support = {DE-AC02-05CH11231//US Department of Energy/International ; P30 GM124169/GM/NIGMS NIH HHS/United States ; }, abstract = {Specificity of interactions between two DNA strands, or between protein and DNA, is often achieved by varying bases or side chains coming off the DNA or protein backbone-for example, the bases participating in Watson-Crick pairing in the double helix, or the side chains contacting DNA in TALEN-DNA complexes. By contrast, specificity of protein-protein interactions usually involves backbone shape complementarity1, which is less modular and hence harder to generalize. Coiled-coil heterodimers are an exception, but the restricted geometry of interactions across the heterodimer interface (primarily at the heptad a and d positions2) limits the number of orthogonal pairs that can be created simply by varying side-chain interactions3,4. Here we show that protein-protein interaction specificity can be achieved using extensive and modular side-chain hydrogen-bond networks. We used the Crick generating equations5 to produce millions of four-helix backbones with varying degrees of supercoiling around a central axis, identified those accommodating extensive hydrogen-bond networks, and used Rosetta to connect pairs of helices with short loops and to optimize the remainder of the sequence. Of 97 such designs expressed in Escherichia coli, 65 formed constitutive heterodimers, and the crystal structures of four designs were in close agreement with the computational models and confirmed the designed hydrogen-bond networks. In cells, six heterodimers were fully orthogonal, and in vitro-following mixing of 32 chains from 16 heterodimer designs, denaturation in 5 M guanidine hydrochloride and reannealing-almost all of the interactions observed by native mass spectrometry were between the designed cognate pairs. The ability to design orthogonal protein heterodimers should enable sophisticated protein-based control logic for synthetic biology, and illustrates that nature has not fully explored the possibilities for programmable biomolecular interaction modalities.}, } @article {pmid30568300, year = {2019}, author = {Murray, NJ and Phinn, SR and DeWitt, M and Ferrari, R and Johnston, R and Lyons, MB and Clinton, N and Thau, D and Fuller, RA}, title = {The global distribution and trajectory of tidal flats.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {222-225}, doi = {10.1038/s41586-018-0805-8}, pmid = {30568300}, issn = {1476-4687}, abstract = {Increasing human populations around the global coastline have caused extensive loss, degradation and fragmentation of coastal ecosystems, threatening the delivery of important ecosystem services1. As a result, alarming losses of mangrove, coral reef, seagrass, kelp forest and coastal marsh ecosystems have occurred1-6. However, owing to the difficulty of mapping intertidal areas globally, the distribution and status of tidal flats-one of the most extensive coastal ecosystems-remain unknown7. Here we present an analysis of over 700,000 satellite images that maps the global extent of and change in tidal flats over the course of 33 years (1984-2016). We find that tidal flats, defined as sand, rock or mud flats that undergo regular tidal inundation7, occupy at least 127,921 km2 (124,286-131,821 km2, 95% confidence interval). About 70% of the global extent of tidal flats is found in three continents (Asia (44% of total), North America (15.5% of total) and South America (11% of total)), with 49.2% being concentrated in just eight countries (Indonesia, China, Australia, the United States, Canada, India, Brazil and Myanmar). For regions with sufficient data to develop a consistent multi-decadal time series-which included East Asia, the Middle East and North America-we estimate that 16.02% (15.62-16.47%, 95% confidence interval) of tidal flats were lost between 1984 and 2016. Extensive degradation from coastal development1, reduced sediment delivery from major rivers8,9, sinking of riverine deltas8,10, increased coastal erosion and sea-level rise11 signal a continuing negative trajectory for tidal flat ecosystems around the world. Our high-spatial-resolution dataset delivers global maps of tidal flats, which substantially advances our understanding of the distribution, trajectory and status of these poorly known coastal ecosystems.}, } @article {pmid30568299, year = {2019}, author = {Karmaus, PWF and Chen, X and Lim, SA and Herrada, AA and Nguyen, TM and Xu, B and Dhungana, Y and Rankin, S and Chen, W and Rosencrance, C and Yang, K and Fan, Y and Cheng, Y and Easton, J and Neale, G and Vogel, P and Chi, H}, title = {Metabolic heterogeneity underlies reciprocal fates of TH17 cell stemness and plasticity.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {101-105}, doi = {10.1038/s41586-018-0806-7}, pmid = {30568299}, issn = {1476-4687}, abstract = {A defining feature of adaptive immunity is the development of long-lived memory T cells to curtail infection. Recent studies have identified a unique stem-like T-cell subset amongst exhausted CD8-positive T cells in chronic infection1-3, but it remains unclear whether CD4-positive T-cell subsets with similar features exist in chronic inflammatory conditions. Amongst helper T cells, TH17 cells have prominent roles in autoimmunity and tissue inflammation and are characterized by inherent plasticity4-7, although how such plasticity is regulated is poorly understood. Here we demonstrate that TH17 cells in a mouse model of autoimmune disease are functionally and metabolically heterogeneous; they contain a subset with stemness-associated features but lower anabolic metabolism, and a reciprocal subset with higher metabolic activity that supports transdifferentiation into TH1-like cells. These two TH17-cell subsets are defined by selective expression of the transcription factors TCF-1 and T-bet, and by discrete levels of CD27 expression. We also identify signalling via the kinase complex mTORC1 as a central regulator of TH17-cell fate decisions by coordinating metabolic and transcriptional programmes. TH17 cells with disrupted mTORC1 signalling or anabolic metabolism fail to induce autoimmune neuroinflammation or to develop into TH1-like cells, but instead upregulate TCF-1 expression and acquire stemness-associated features. Single-cell RNA sequencing and experimental validation reveal heterogeneity in fate-mapped TH17 cells, and a developmental arrest in the TH1 transdifferentiation trajectory upon loss of mTORC1 activity or metabolic perturbation. Our results establish that the dichotomy of stemness and effector function underlies the heterogeneous TH17 responses and autoimmune pathogenesis, and point to previously unappreciated metabolic control of plasticity in helper T cells.}, } @article {pmid30568285, year = {2019}, author = {Strassburg, BBN and Beyer, HL and Crouzeilles, R and Iribarrem, A and Barros, F and de Siqueira, MF and Sánchez-Tapia, A and Balmford, A and Sansevero, JBB and Brancalion, PHS and Broadbent, EN and Chazdon, RL and Filho, AO and Gardner, TA and Gordon, A and Latawiec, A and Loyola, R and Metzger, JP and Mills, M and Possingham, HP and Rodrigues, RR and Scaramuzza, CAM and Scarano, FR and Tambosi, L and Uriarte, M}, title = {Strategic approaches to restoring ecosystems can triple conservation gains and halve costs.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {62-70}, doi = {10.1038/s41559-018-0743-8}, pmid = {30568285}, issn = {2397-334X}, abstract = {International commitments for ecosystem restoration add up to one-quarter of the world's arable land. Fulfilling them would ease global challenges such as climate change and biodiversity decline but could displace food production and impose financial costs on farmers. Here, we present a restoration prioritization approach capable of revealing these synergies and trade-offs, incorporating ecological and economic efficiencies of scale and modelling specific policy options. Using an actual large-scale restoration target of the Atlantic Forest hotspot, we show that our approach can deliver an eightfold increase in cost-effectiveness for biodiversity conservation compared with a baseline of non-systematic restoration. A compromise solution avoids 26% of the biome's current extinction debt of 2,864 plant and animal species (an increase of 257% compared with the baseline). Moreover, this solution sequesters 1 billion tonnes of CO2-equivalent (a 105% increase) while reducing costs by US$28 billion (a 57% decrease). Seizing similar opportunities elsewhere would offer substantial contributions to some of the greatest challenges for humankind.}, } @article {pmid30568282, year = {2019}, author = {Yang, Z and Jiang, B and McNamara, ME and Kearns, SL and Pittman, M and Kaye, TG and Orr, PJ and Xu, X and Benton, MJ}, title = {Pterosaur integumentary structures with complex feather-like branching.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {24-30}, doi = {10.1038/s41559-018-0728-7}, pmid = {30568282}, issn = {2397-334X}, abstract = {Pterosaurs were the first vertebrates to achieve true flapping flight, but in the absence of living representatives, many questions concerning their biology and lifestyle remain unresolved. Pycnofibres-the integumentary coverings of pterosaurs-are particularly enigmatic: although many reconstructions depict fur-like coverings composed of pycnofibres, their affinities and function are not fully understood. Here, we report the preservation in two anurognathid pterosaur specimens of morphologically diverse pycnofibres that show diagnostic features of feathers, including non-vaned grouped filaments and bilaterally branched filaments, hitherto considered unique to maniraptoran dinosaurs, and preserved melanosomes with diverse geometries. These findings could imply that feathers had deep evolutionary origins in ancestral archosaurs, or that these structures arose independently in pterosaurs. The presence of feather-like structures suggests that anurognathids, and potentially other pterosaurs, possessed a dense filamentous covering that probably functioned in thermoregulation, tactile sensing, signalling and aerodynamics.}, } @article {pmid30568221, year = {2018}, author = {}, title = {Antarctic deaths, private-funding crackdown and gene-editing call.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {306-307}, doi = {10.1038/d41586-018-07757-4}, pmid = {30568221}, issn = {1476-4687}, } @article {pmid30568220, year = {2018}, author = {Gewin, V}, title = {Milestone meetings.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S86-S87}, doi = {10.1038/d41586-018-07781-4}, pmid = {30568220}, issn = {1476-4687}, } @article {pmid30568219, year = {2018}, author = {Sohn, E}, title = {The future of the scientific conference.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S80-S82}, doi = {10.1038/d41586-018-07779-y}, pmid = {30568219}, issn = {1476-4687}, } @article {pmid30568218, year = {2018}, author = {Fleming, N}, title = {How to give a great scientific talk.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S84-S85}, doi = {10.1038/d41586-018-07780-5}, pmid = {30568218}, issn = {1476-4687}, } @article {pmid30568217, year = {2018}, author = {Gould, J}, title = {How conferences are getting better at accommodating child-caring scientists.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S88-S89}, doi = {10.1038/d41586-018-07782-3}, pmid = {30568217}, issn = {1476-4687}, mesh = {Child ; *Child Care ; Congresses as Topic ; Humans ; }, } @article {pmid30568216, year = {2018}, author = {Leeming, J}, title = {The 2019 Events Guide.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S79}, doi = {10.1038/d41586-018-07778-z}, pmid = {30568216}, issn = {1476-4687}, } @article {pmid30568215, year = {2018}, author = {Parkes, E}, title = {Make it easier for me to deliver childcare at conferences.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S89}, doi = {10.1038/d41586-018-07783-2}, pmid = {30568215}, issn = {1476-4687}, mesh = {Child ; *Child Care ; Congresses as Topic ; Humans ; }, } @article {pmid30568214, year = {2018}, author = {Khan, SA}, title = {King Faisal international prize a harbinger of Nobel winners?.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {345}, doi = {10.1038/d41586-018-07805-z}, pmid = {30568214}, issn = {1476-4687}, } @article {pmid30568213, year = {2018}, author = {Knoepfler, P}, title = {Gene editing: sloppy definitions mislead.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {345}, doi = {10.1038/d41586-018-07802-2}, pmid = {30568213}, issn = {1476-4687}, mesh = {CRISPR-Cas Systems ; *Gene Editing ; *Genome ; }, } @article {pmid30568212, year = {2018}, author = {Moorthy, V and Salama, P and Swaminathan, S}, title = {Up for debate - WHO guidelines on prompt release of outbreak data.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {345}, doi = {10.1038/d41586-018-07803-1}, pmid = {30568212}, issn = {1476-4687}, } @article {pmid30568211, year = {2018}, author = {Wang, H and Li, J and Li, W and Gao, C and Wei, W}, title = {CRISPR twins: a condemnation from Chinese academic societies.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {345}, doi = {10.1038/d41586-018-07777-0}, pmid = {30568211}, issn = {1476-4687}, mesh = {*Clustered Regularly Interspaced Short Palindromic Repeats ; Humans ; Organizations ; Societies ; *Twins ; }, } @article {pmid30568210, year = {2018}, author = {Davies, J and Stoett, P}, title = {Biodiversity loss is dire, don't get distracted.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {345}, doi = {10.1038/d41586-018-07804-0}, pmid = {30568210}, issn = {1476-4687}, } @article {pmid30568209, year = {2018}, author = {Gilbey, J}, title = {Solstice.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {462}, doi = {10.1038/d41586-018-07808-w}, pmid = {30568209}, issn = {1476-4687}, } @article {pmid30568208, year = {2018}, author = {Žumer, S}, title = {Elusive torque sensed by liquid crystals.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {350-351}, doi = {10.1038/d41586-018-07744-9}, pmid = {30568208}, issn = {1476-4687}, } @article {pmid30568207, year = {2018}, author = {Drew, L}, title = {Liver cirrhosis: scar wars.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S73}, doi = {10.1038/d41586-018-07759-2}, pmid = {30568207}, issn = {1476-4687}, } @article {pmid30568206, year = {2018}, author = {Drew, L}, title = {Tipping the balance.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {S74-S75}, doi = {10.1038/d41586-018-07760-9}, pmid = {30568206}, issn = {1476-4687}, } @article {pmid30568205, year = {2018}, author = {Karakas, A}, title = {An abundance of rare isotopes in a planetary nebula.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {353-354}, doi = {10.1038/d41586-018-07726-x}, pmid = {30568205}, issn = {1476-4687}, } @article {pmid30568204, year = {2018}, author = {Woolston, C}, title = {Seven steps to boost your research career in 2019.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {449-450}, doi = {10.1038/d41586-018-07807-x}, pmid = {30568204}, issn = {1476-4687}, } @article {pmid30568203, year = {2018}, author = {Fu, J and Ren, Z and Bacsa, J and Musaev, DG and Davies, HML}, title = {Desymmetrization of cyclohexanes by site- and stereoselective C-H functionalization.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {395-399}, doi = {10.1038/s41586-018-0799-2}, pmid = {30568203}, issn = {1476-4687}, support = {CHE-1700982//National Science Foundation/International ; CHE-0958205//National Science Foundation/International ; CHE-1531620//National Science Foundation/International ; CHE-1626172//National Science Foundation/International ; }, abstract = {Carbon-hydrogen (C-H) bonds have long been considered unreactive and are inert to traditional chemical reagents, yet new methods for the transformation of these bonds are continually being developed1-9. However, it is challenging to achieve such transformations in a highly selective manner, especially if the C-H bonds are unactivated10 or not adjacent to a directing group11-13. Catalyst-controlled site-selectivity-in which the inherent reactivities of the substrates14 can be overcome by choosing an appropriate catalyst-is an appealing concept, and substantial effort has been made towards catalyst-controlled C-H functionalization6,15-17, in particular methylene C-H bond functionalization. However, although several new methods have targeted these bonds in cyclic alkanes, the selectivity has been relatively poor18-20. Here we illustrate an additional level of sophistication in catalyst-controlled C-H functionalization, whereby unactivated cyclohexane derivatives can be desymmetrized in a highly site- and stereoselective manner through donor/acceptor carbene insertion. These studies demonstrate the potential of catalyst-controlled site-selectivity to govern which C-H bond will react, which could enable new strategies for the production of fine chemicals.}, } @article {pmid30568202, year = {2018}, author = {Janak, P}, title = {Brain circuits of compulsive drug addiction identified.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {349-350}, doi = {10.1038/d41586-018-07716-z}, pmid = {30568202}, issn = {1476-4687}, } @article {pmid30568201, year = {2018}, author = {Lewis-Jones, H}, title = {Explorers at sea: centuries of science afloat.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {340-342}, doi = {10.1038/d41586-018-07776-1}, pmid = {30568201}, issn = {1476-4687}, } @article {pmid30568200, year = {2018}, author = {Hills, R and Kulkarni, G and Meerburg, PD and Puchwein, E}, title = {Concerns about modelling of the EDGES data.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {E32-E34}, doi = {10.1038/s41586-018-0796-5}, pmid = {30568200}, issn = {1476-4687}, } @article {pmid30568199, year = {2018}, author = {Bowman, JD and Rogers, AEE and Monsalve, RA and Mozdzen, TJ and Mahesh, N}, title = {Reply to Hills et al.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {E35}, doi = {10.1038/s41586-018-0797-4}, pmid = {30568199}, issn = {1476-4687}, } @article {pmid30568198, year = {2018}, author = {Lin, JF and Mao, Z and Yang, J and Fu, S}, title = {Elasticity of lower-mantle bridgmanite.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {E18-E26}, doi = {10.1038/s41586-018-0741-7}, pmid = {30568198}, issn = {1476-4687}, } @article {pmid30568197, year = {2018}, author = {Kurnosov, A and Marquardt, H and Frost, DJ and Ballaran, TB and Ziberna, L}, title = {Kurnosov et al. reply.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {E27-E31}, doi = {10.1038/s41586-018-0742-6}, pmid = {30568197}, issn = {1476-4687}, } @article {pmid30568196, year = {2018}, author = {Piecuch, CG and Huybers, P and Hay, CC and Kemp, AC and Little, CM and Mitrovica, JX and Ponte, RM and Tingley, MP}, title = {Origin of spatial variation in US East Coast sea-level trends during 1900-2017.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {400-404}, doi = {10.1038/s41586-018-0787-6}, pmid = {30568196}, issn = {1476-4687}, support = {1558939//National Science Foundation/International ; 1558966//National Science Foundation/International ; 1458921//National Science Foundation/International ; NNH16CT01C/NASA/NASA/United States ; NNX17AE17G/NASA/NASA/United States ; 80NSSC17K0098/NASA/NASA/United States ; }, abstract = {Identifying the causes of historical trends in relative sea level-the height of the sea surface relative to Earth's crust-is a prerequisite for predicting future changes. Rates of change along the eastern coast of the USA (the US East Coast) during the past century were spatially variable, and relative sea level rose faster along the Mid-Atlantic Bight than along the South Atlantic Bight and the Gulf of Maine. Past studies suggest that Earth's ongoing response to the last deglaciation1-5, surface redistribution of ice and water5-9 and changes in ocean circulation9-13 contributed considerably to this large-scale spatial pattern. Here we analyse instrumental data14,15 and proxy reconstructions4,12 using probabilistic methods16-18 to show that vertical motions of Earth's crust exerted the dominant control on regional spatial differences in relative sea-level trends along the US East Coast during 1900-2017, explaining most of the large-scale spatial variance. Rates of coastal subsidence caused by ongoing relaxation of the peripheral forebulge associated with the last deglaciation are strongest near North Carolina, Maryland and Virginia. Such structure indicates that Earth's elastic lithosphere is thicker than has been assumed in other models19-22. We also find a substantial coastal gradient in relative sea-level trends over this period that is unrelated to deglaciation and suggests contributions from twentieth-century redistribution of ice and water. Our results indicate that the majority of large-scale spatial variation in long-term rates of relative sea-level rise on the US East Coast is due to geological processes that will persist at similar rates for centuries.}, } @article {pmid30568195, year = {2018}, author = {Scamps, G and Simenel, C}, title = {Impact of pear-shaped fission fragments on mass-asymmetric fission in actinides.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {382-385}, doi = {10.1038/s41586-018-0780-0}, pmid = {30568195}, issn = {1476-4687}, abstract = {Nuclear fission of heavy (actinide) nuclei results predominantly in asymmetric mass splits1. Without quantum shell effects, which can give extra binding energy to their mass-asymmetric shapes, these nuclei would fission symmetrically. The strongest shell effects appear in spherical nuclei, such as the spherical 'doubly magic' (that is, both its atomic and neutron numbers are 'magic' numbers) nucleus 132Sn, which contains 50 protons and 82 neutrons. However, a systematic study of fission2 has shown that heavy fission fragments have atomic numbers distributed around Z = 52 to Z = 56, indicating that the strong shell effects in 132Sn are not the only factor affecting actinide fission. Reconciling the strong spherical shell effects at Z = 50 with the different Z values of fission fragments observed in nature has been a longstanding puzzle3. Here we show that the final mass asymmetry of the fragments is also determined by the extra stability provided by octupole (pear-shaped) deformations, which have been recently confirmed experimentally around 144Ba (Z = 56)4,5, one of very few nuclei with shell-stabilized octupole deformation6. Using a quantum many-body model of superfluid fission dynamics7, we find that heavy fission fragments are produced predominantly with 52 to 56 protons, which is associated with substantial octupole deformation acquired on the way to fission. These octupole shapes, which favour asymmetric fission, are induced by deformed shells at Z = 52 and Z = 56. By contrast, spherical magic nuclei are very resistant to octupole deformation, which hinders their production as fission fragments. These findings may explain surprising observations of asymmetric fission in nuclei lighter than lead8.}, } @article {pmid30568194, year = {2018}, author = {Somers, DAT and Garrett, JL and Palm, KJ and Munday, JN}, title = {Measurement of the Casimir torque.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {386-389}, doi = {10.1038/s41586-018-0777-8}, pmid = {30568194}, issn = {1476-4687}, support = {PHY-1506047//National Science Foundation/International ; PHY-1806768//National Science Foundation/International ; }, abstract = {Intermolecular forces are pervasive in nature and give rise to various phenomena including surface wetting1, adhesive forces in biology2,3, and the Casimir effect4, which causes two charge-neutral, metal objects in vacuum to attract each other. These interactions are the result of quantum fluctuations of electromagnetic waves and the boundary conditions imposed by the interacting materials. When the materials are optically anisotropic, different polarizations of light experience different refractive indices and a torque is expected to occur that causes the materials to rotate to a position of minimum energy5,6. Although predicted more than four decades ago, the small magnitude of the Casimir torque has so far prevented direct measurements of it. Here we experimentally measure the Casimir torque between two optically anisotropic materials-a solid birefringent crystal (calcite, lithium niobite, rutile or yttrium vanadate) and a liquid crystal (5CB). We control the sign and strength of the torque, and its dependence on the rotation angle and the separation distance between the materials, through the choice of materials. The values that we measure agree with calculations, verifying the long-standing prediction that a mechanical torque induced by quantum fluctuations can exist between two separated objects. These results open the door to using the Casimir torque as a micro- or nanoscale actuation mechanism, which would be relevant for a range of technologies, including microelectromechanical systems and liquid crystals.}, } @article {pmid30568193, year = {2018}, author = {Schmidt, DR and Woolf, NJ and Zega, TJ and Ziurys, LM}, title = {Extreme 13C,15N and 17O isotopic enrichment in the young planetary nebula K4-47.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {378-381}, doi = {10.1038/s41586-018-0763-1}, pmid = {30568193}, issn = {1476-4687}, abstract = {Carbon, nitrogen and oxygen are the three most abundant elements in the Galaxy after hydrogen and helium. Whereas hydrogen and helium were created in the Big Bang, carbon, nitrogen and oxygen arise from nucleosynthesis in stars. Of particular interest1,2 are the isotopic ratios 12C/13C, 14N/15N and 16O/17O because they are effective tracers of nucleosynthesis and help to benchmark the chemical processes that occurred in primitive interstellar material as it evolved into our Solar System3. However, the origins of the rare isotopes 15N and 17O remain uncertain, although novae and very massive stars that explode as supernovae are postulated4-6 to be the main sources of 15N. Here we report millimetre-wavelength observations of the young bipolar planetary nebula K4-47 that indicate another possible source for these isotopes. We identify various carbon-bearing molecules in K4-47 that show that this object is carbon-rich, and find unusually high enrichment in rare carbon (13C), oxygen (17O) and nitrogen (15N) isotopes: 12C/13C = 2.2 ± 0.8, 16O/17O = 21.4 ± 10.3 and 14N/15N = 13.6 ± 6.5 (uncertainties are three standard deviations); for comparison, the corresponding solar ratios7 are 89.4 ± 0.2, 2,632 ± 7 and 435 ± 57. One possible interpretation of these results is that K4-47 arose from a J-type asymptotic giant branch star that underwent a helium-shell flash (an explosive nucleosynthetic event that converts large quantities of helium to carbon and other elements), enriching the resulting planetary nebula in 15N and 17O and creating its bipolar geometry. Other possible explanations are that K4-47 is a binary system or that it resulted from a white dwarf merger, as has been suggested for object CK Vul8. These results suggest that nucleosynthesis of carbon, nitrogen and oxygen is not well understood and that the classification of certain stardust grains must be reconsidered.}, } @article {pmid30568192, year = {2018}, author = {Pascoli, V and Hiver, A and Van Zessen, R and Loureiro, M and Achargui, R and Harada, M and Flakowski, J and Lüscher, C}, title = {Stochastic synaptic plasticity underlying compulsion in a model of addiction.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {366-371}, doi = {10.1038/s41586-018-0789-4}, pmid = {30568192}, issn = {1476-4687}, abstract = {Activation of the mesolimbic dopamine system reinforces goal-directed behaviours. With repetitive stimulation-for example, by chronic drug abuse-the reinforcement may become compulsive and intake continues even in the face of major negative consequences. Here we gave mice the opportunity to optogenetically self-stimulate dopaminergic neurons and observed that only a fraction of mice persevered if they had to endure an electric shock. Compulsive lever pressing was associated with an activity peak in the projection terminals from the orbitofrontal cortex (OFC) to the dorsal striatum. Although brief inhibition of OFC neurons temporarily relieved compulsive reinforcement, we found that transmission from the OFC to the striatum was permanently potentiated in persevering mice. To establish causality, we potentiated these synapses in vivo in mice that stopped optogenetic self-stimulation of dopamine neurons because of punishment; this led to compulsive lever pressing, whereas depotentiation in persevering mice had the converse effect. In summary, synaptic potentiation of transmission from the OFC to the dorsal striatum drives compulsive reinforcement, a defining symptom of addiction.}, } @article {pmid30568027, year = {2018}, author = {Gronwald, T and Velasques, B and Ribeiro, P and Machado, S and Murillo-Rodríguez, E and Ludyga, S and Yamamoto, T and Budde, H}, title = {Increasing exercise's effect on mental health: Exercise intensity does matter.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11890-E11891}, doi = {10.1073/pnas.1818161115}, pmid = {30568027}, issn = {1091-6490}, mesh = {Dentate Gyrus ; *Exercise ; Humans ; *Mental Health ; }, } @article {pmid30568025, year = {2018}, author = {Redd, NT}, title = {Inner Workings: Astronomers track dwarf galaxies to better understand the Milky Way's make-up and evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12836-12838}, doi = {10.1073/pnas.1817136115}, pmid = {30568025}, issn = {1091-6490}, } @article {pmid30568024, year = {2018}, author = {Vaidyanathan, G}, title = {Science and Culture: Imagining a climate-change future, without the dystopia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12832-12835}, doi = {10.1073/pnas.1819792116}, pmid = {30568024}, issn = {1091-6490}, } @article {pmid30567977, year = {2019}, author = {Mietke, A and Jülicher, F and Sbalzarini, IF}, title = {Self-organized shape dynamics of active surfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {29-34}, doi = {10.1073/pnas.1810896115}, pmid = {30567977}, issn = {1091-6490}, abstract = {Mechanochemical processes in thin biological structures, such as the cellular cortex or epithelial sheets, play a key role during the morphogenesis of cells and tissues. In particular, they are responsible for the dynamical organization of active stresses that lead to flows and deformations of the material. Consequently, advective transport redistributes force-generating molecules and thereby contributes to a complex mechanochemical feedback loop. It has been shown in fixed geometries that this mechanism enables patterning, but the interplay of these processes with shape changes of the material remains to be explored. In this work, we study the fully self-organized shape dynamics using the theory of active fluids on deforming surfaces and develop a numerical approach to solve the corresponding force and torque balance equations. We describe the spontaneous generation of nontrivial surface shapes, shape oscillations, and directed surface flows that resemble peristaltic waves from self-organized, mechanochemical processes on the deforming surface. Our approach provides opportunities to explore the dynamics of self-organized active surfaces and can help to understand the role of shape as an integral element of the mechanochemical organization of morphogenetic processes.}, } @article {pmid30567976, year = {2019}, author = {Schönke, J and Fried, E}, title = {Single degree of freedom everting ring linkages with nonorientable topology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {90-95}, doi = {10.1073/pnas.1809796115}, pmid = {30567976}, issn = {1091-6490}, abstract = {Linkages are assemblies of rigid bodies connected through joints. They serve as the basis for force- and movement-managing devices ranging from ordinary pliers to high-precision robotic arms. Aside from planar mechanisms, like the well-known four-bar linkage, only a few linkages with a single internal degree of freedom-meaning that they can change shape in only one way and may thus be easily controlled-have been known to date. Here, we present "Möbius kaleidocycles," a previously undiscovered class of single-internal degree of freedom ring linkages containing nontrivial examples of spatially underconstrained mechanisms. A Möbius kaleidocycle is made from seven or more identical links joined by revolute hinges. These links dictate a specific twist angle between neighboring hinges, and the hinge orientations induce a nonorientable topology equivalent to the topology of a [Formula: see text]-twist Möbius band. Apart from having many technological applications, including perhaps the design of organic ring molecules with peculiar electronic properties, Möbius kaleidocycles raise fundamental questions about geometry, topology, and the limitations of mobility for closed loop linkages.}, } @article {pmid30567975, year = {2019}, author = {Tekwa, EW and Fenichel, EP and Levin, SA and Pinsky, ML}, title = {Path-dependent institutions drive alternative stable states in conservation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {689-694}, doi = {10.1073/pnas.1806852116}, pmid = {30567975}, issn = {1091-6490}, abstract = {Understanding why some renewable resources are overharvested while others are conserved remains an important challenge. Most explanations focus on institutional or ecological differences among resources. Here, we provide theoretical and empirical evidence that conservation and overharvest can be alternative stable states within the same exclusive-resource management system because of path-dependent processes, including slow institutional adaptation. Surprisingly, this theory predicts that the alternative states of strong conservation or overharvest are most likely for resources that were previously thought to be easily conserved under optimal management or even open access. Quantitative analyses of harvest rates from 217 intensely managed fisheries supports the predictions. Fisheries' harvest rates also showed transient dynamics characteristic of path dependence, as well as convergence to the alternative stable state after unexpected transitions. This statistical evidence for path dependence differs from previous empirical support that was based largely on case studies, experiments, and distributional analyses. Alternative stable states in conservation appear likely outcomes for many cooperatively managed renewable resources, which implies that achieving conservation outcomes hinges on harnessing existing policy tools to navigate transitions.}, } @article {pmid30567974, year = {2019}, author = {Maupin-Furlow, JA}, title = {Stepping up protein degradation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {350-352}, doi = {10.1073/pnas.1819949116}, pmid = {30567974}, issn = {1091-6490}, } @article {pmid30567973, year = {2019}, author = {Rigoulet, M and Massou, S and Sosa Carrizo, ED and Mallet-Ladeira, S and Amgoune, A and Miqueu, K and Bourissou, D}, title = {Evidence for genuine hydrogen bonding in gold(I) complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {46-51}, doi = {10.1073/pnas.1817194116}, pmid = {30567973}, issn = {1091-6490}, abstract = {The ability of gold to act as proton acceptor and participate in hydrogen bonding remains an open question. Here, we report the synthesis and characterization of cationic gold(I) complexes featuring ditopic phosphine-ammonium (P,NH+) ligands. In addition to the presence of short Au∙∙∙H contacts in the solid state, the presence of Au∙∙∙H-N hydrogen bonds was inferred by NMR and IR spectroscopies. The bonding situation was extensively analyzed computationally. All features were consistent with the presence of three-center four-electron attractive interactions combining electrostatic and orbital components. The role of relativistic effects was examined, and the analysis is extended to other recently described gold(I) complexes.}, } @article {pmid30567596, year = {2018}, author = {Moolhuijzen, P and See, PT and Moffat, CS}, title = {Exploration of wheat and pathogen transcriptomes during tan spot infection.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {907}, doi = {10.1186/s13104-018-3993-2}, pmid = {30567596}, issn = {1756-0500}, support = {CUR00023//Grains Research and Development Corporation/ ; }, abstract = {OBJECTIVES: The fungus Pyrenophora tritici-repentis is the causal agent of tan spot, a major disease of wheat (Triticum aestivum). Here, we used RNA sequencing to generate transcriptional datasets for both the host and pathogen during infection and during in vitro pathogen growth stages.

DATA DESCRIPTION: To capture gene expression during wheat infection with the P. tritici-repentis isolate M4, RNA datasets were generated for wheat inoculated with P. tritici-repentis (infection) and a mock (control) at 3 and 4 days post-infection, when scorable leaf disease symptoms manifest. The P. tritici-repentis isolate M4 was also RNA sequenced to capture gene expression in vitro at two different growth stages: 7-day old vegetative mycelia and 9-day old sporulating mycelia, to coincide with a latent growth stage and early sporulation respectively. In total, 6 RNA datasets are available to aid in the validation of predicted genes of P. tritici-repentis and wheat. The datasets generated offer an insight into the transcriptomic profile of the host-pathogen interaction and can be used to investigate the expression of a subset of transcripts or targeted genes prior to designing cost-intensive RNA sequencing experiments, that would be best further explored with replication and a time series analysis.}, } @article {pmid30567589, year = {2018}, author = {Geremew, D and Tajebe, F and Ambachew, S and Endalamaw, A and Eshetie, S}, title = {Seroprevalence of HIV among pregnant women in Ethiopia: a systematic review and meta-analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {908}, doi = {10.1186/s13104-018-4022-1}, pmid = {30567589}, issn = {1756-0500}, abstract = {OBJECTIVE: This systematic review and meta-analysis aimed to determine the pooled prevalence of HIV among pregnant women in Ethiopia.

RESULT: PubMed, EMBASE, Science Direct and Google scholar databases were searched to retrieve 15 relevant articles based on the inclusion criteria. A total of 13,746 participants were included in the original studies and considered in this analysis. Among subjects, 717 were infected with HIV only, and 12 were HIV-HBV co-infected pregnant women. In this meta-analysis, the pooled prevalence of HIV among pregnant women in Ethiopia was 5.74% (95% CI 3.96-7.53%). Regional analysis showed that 9.50% (95% CI 7.76-11.23%) in Amhara, 4.80% (95% CI 3.12-6.49%) in Addis Ababa, 2.14% (95% CI - 0.54 to 4.82%) in SNNP and 4.48% (95% CI 2.56-6.41%) in Oromia region. Besides, six studies reported HIV-HBV co-infection and the pooled prevalence was 0.68% (95% CI 0.27-1.08%) among pregnant women in Ethiopia.}, } @article {pmid30567583, year = {2018}, author = {Soghaier, MA and Abdelgadir, DM and Abdelkhalig, SM and Kafi, H and Zarroug, IMA and Sall, AA and Eldegai, MH and Elageb, RM and Osman, MM and Khogali, H}, title = {Evidence of pre-existing active Zika virus circulation in Sudan prior to 2012.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {906}, doi = {10.1186/s13104-018-4027-9}, pmid = {30567583}, issn = {1756-0500}, abstract = {OBJECTIVE: The purpose of this study is to provide the first evidence of Zika virus circulation (ZIK) in Sudan. Zika virus was first isolated in the Zika forest of Uganda in 1947, and in 2016, the World Health Assembly declared it a public health emergency of international concern. The discovery of Zika virus circulation in Sudan came as a secondary finding in a 2012 country-wide yellow fever prevalence study, when laboratory tests were done to exclude cross-reactions between flaviviruses. The study was cross-sectional community-based, with randomly selected participants through multi-stage cluster sampling. A sub-set of samples were tested for the Zika virus using ELISA, and the ones that demonstrated reactive results were subsequently tested by PRNT.

RESULTS: The prevalence of Zika IgG antibodies among ELISA-tested samples was 62.7% (59.4 to 66.1, 95% CI), and only one sample was found positive when tested by PRNT. This provided the first documented evidence for the pre-existing circulation of Zika virus circulation in Sudan. This evidence provides the foundation for future research in this field, and further structured studies should be conducted to determine the epidemiology and burden of the disease.}, } @article {pmid30567551, year = {2018}, author = {Colombo, M and Castilho, NPA and Todorov, SD and Nero, LA}, title = {Beneficial properties of lactic acid bacteria naturally present in dairy production.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {219}, doi = {10.1186/s12866-018-1356-8}, pmid = {30567551}, issn = {1471-2180}, abstract = {BACKGROUND: Consumers are increasingly demanding for natural and beneficial foods, in order to improve their health and well-being. Probiotics play an important role in such demand, and dairy foods are commonly used as vehicles for such bacteria, represented predominantly by lactic acid bacteria. Due to consumers demand, food industry is constantly looking for novel bacterial strains, leading to studies that aims the isolation and characterization of their beneficial features. This study aimed to characterize the naturally occurring lactic acid bacteria obtained from a dairy environment, in order to assess their potential use as probiotics.

RESULTS: Preliminary screening and PCR analysis, based on 16S rRNA sequencing, were applied to select and identify 15 LAB strains from the genera Lactobacillus (n = 11), Pediococcus (n = 2) and Weissella (n = 2). All strains showed resistance to low pH and the evaluated bile salt concentrations in vitro. The API ZYM test characterized the enzymatic activity of the strains, and a high β-galactosidase activity was observed in 13 strains. All strains presented resistance to simulated gastric (3 h) and intestinal (4 h) conditions in vitro, the ability to auto- and co-aggregate with indicator microorganisms and a high cell surface hydrophobicity. Most of the strains were positive for map and EFTu beneficial genes. All strains exhibited strong deconjugation of bile salts in vitro and all assimilated lactose.

CONCLUSIONS: The phenotypes exhibited in vitro and the presence of beneficial genes revealed the beneficial potential of the studied strains, demanding further analyses in a food matrix and in vivo to allow the development of a functional product, with health-related properties.}, } @article {pmid30567522, year = {2018}, author = {Bacher, MG and Fenton, O and Bondi, G and Creamer, RE and Karmarkar, M and Schmidt, O}, title = {The impact of cattle dung pats on earthworm distribution in grazed pastures.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {59}, doi = {10.1186/s12898-018-0216-6}, pmid = {30567522}, issn = {1472-6785}, support = {13/S/468//Irish Department of Agriculture, Food and the Marine/ ; }, abstract = {BACKGROUND: Grazed grassland management regimes can have various effects on soil fauna. For example, effects on earthworms can be negative through compaction induced by grazing animals, or positive mediated by increases in sward productivity and cattle dung pats providing a food source. Knowledge gaps exist in relation to the behaviour of different earthworm species i.e. their movement towards and aggregation under dung pats, the legacy effects of pats and the spatial area of recruitment. The present study addressed these knowledge gaps in field experiments, over 2 years, using natural and simulated dung pats on two permanent, intensively grazed pastures in Ireland.

RESULTS: Dung pats strongly affected spatial earthworm distribution, with up to four times more earthworms aggregating beneath pats, than in the control locations away from pats. In these earthworm communities comprising 11 species, temporally different aggregation and dispersal patterns were observed, including absence of individual species from control locations, but no clear successional responses. Epigeic species in general, but also certain species of the anecic and endogeic groups were aggregating under dung. Sampling after complete dung pat disappearance (27 weeks after application) suggested an absence of a dung pat legacy effect on earthworm communities. Based on species distributions, the maximum size of the recruitment area from which earthworms moved to pats was estimated to be 3.8 m2 per dung pat. Since actual grazing over 6 weeks would result in the deposition of about 300 dung pats per ha, it is estimated that a surface area of 1140 m2 or about 11% of the total grazing area can be influenced by dung pats in a given grazing period.

CONCLUSIONS: This study showed that the presence of dung pats in pastures creates temporary hot spots in spatial earthworm species distribution, which changes over time. The findings highlight the importance of considering dung pats, temporally and spatially, when sampling earthworms in grazed pastures. Published comparisons of grazed and cut grasslands probably reached incorrect conclusions by ignoring or deliberately avoiding dung pats. Furthermore, the observed intense aggregation of earthworms beneath dung pats suggests that earthworm functions need to be assessed separately at these hot spots.}, } @article {pmid30567500, year = {2018}, author = {Barreto, DM and Barros, GS and Santos, LABO and Soares, RC and Batista, MVA}, title = {Comparative transcriptomic analysis of bovine papillomatosis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {949}, doi = {10.1186/s12864-018-5361-y}, pmid = {30567500}, issn = {1471-2164}, support = {446425/2014-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 23038.010050/2013-04//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 8444/2013-02//Fundação de Apoio à Pesquisa e à Inovação Tecnológica do Estado de Sergipe/ ; }, abstract = {BACKGROUND: Bovine papillomavirus (BPV) belongs to the Papillomaviridae family and infects epithelial cells of bovines and closely related animals, causing hyperproliferative lesions known as warts or papillomas, which may regress or progress to form benign or malignant tumors. The virus enters the host cell and interacts with it by altering the regulation of genes that are responsible for controlling the cell cycle, thus triggering lesion formation. It is not yet known which host genes are regulated by viral infection. Therefore, the objective of this study was to make use of next-generation RNA sequencing methods to identify differentially expressed genes associated with BPV infection, which might elucidate possible marker genes that could be used to control the disease.

RESULTS: Transcriptome analysis revealed that 1343 genes were differentially regulated (FDR < 0.05). A comparison of gene expression in infected and noninfected cows indicated that 655 genes were significantly upregulated, and 688 genes were significantly downregulated. Most differentially expressed genes were associated with BPV infection pathways, which supports the hypothesis that viral infection was the mechanism associated with this regulation.

CONCLUSIONS: This is the first study that focused on a large-scale evaluation of gene expression associated with BPV infection, which is important to identify possible metabolic pathways regulated by host genes for lesion development. In addition, novel targets could be identified in order to find ligands that interact with BPV, with the aim of interrupting the infection cycle.}, } @article {pmid30567498, year = {2018}, author = {Griesemer, M and Kimbrel, JA and Zhou, CE and Navid, A and D'haeseleer, P}, title = {Combining multiple functional annotation tools increases coverage of metabolic annotation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {948}, doi = {10.1186/s12864-018-5221-9}, pmid = {30567498}, issn = {1471-2164}, support = {DE-AC52-07NA27344//National Nuclear Security Administration/ ; SCW1039-02//Biological and Environmental Research/ ; }, abstract = {BACKGROUND: Genome-scale metabolic modeling is a cornerstone of systems biology analysis of microbial organisms and communities, yet these genome-scale modeling efforts are invariably based on incomplete functional annotations. Annotated genomes typically contain 30-50% of genes without functional annotation, severely limiting our knowledge of the "parts lists" that the organisms have at their disposal. These incomplete annotations may be sufficient to derive a model of a core set of well-studied metabolic pathways that support growth in pure culture. However, pathways important for growth on unusual metabolites exchanged in complex microbial communities are often less understood, resulting in missing functional annotations in newly sequenced genomes.

RESULTS: Here, we present results on a comprehensive reannotation of 27 bacterial reference genomes, focusing on enzymes with EC numbers annotated by KEGG, RAST, EFICAz, and the BRENDA enzyme database, and on membrane transport annotations by TransportDB, KEGG and RAST. Our analysis shows that annotation using multiple tools can result in a drastically larger metabolic network reconstruction, adding on average 40% more EC numbers, 3-8 times more substrate-specific transporters, and 37% more metabolic genes. These results are even more pronounced for bacterial species that are phylogenetically distant from well-studied model organisms such as E. coli.

CONCLUSIONS: Metabolic annotations are often incomplete and inconsistent. Combining multiple functional annotation tools can greatly improve genome coverage and metabolic network size, especially for non-model organisms and non-core pathways.}, } @article {pmid30567492, year = {2018}, author = {Ehsani, R and Drabløs, F}, title = {Measures of co-expression for improved function prediction of long non-coding RNAs.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {533}, doi = {10.1186/s12859-018-2546-y}, pmid = {30567492}, issn = {1471-2105}, support = {-//NTNU - Norwegian University of Science and Technology/ ; -//University of Zabol/ ; }, mesh = {Computational Biology/*methods ; *Gene Expression Profiling ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing ; Humans ; *Molecular Sequence Annotation ; RNA, Long Noncoding/genetics/*metabolism ; *Software ; }, abstract = {BACKGROUND: Almost 16,000 human long non-coding RNA (lncRNA) genes have been identified in the GENCODE project. However, the function of most of them remains to be discovered. The function of lncRNAs and other novel genes can be predicted by identifying significantly enriched annotation terms in already annotated genes that are co-expressed with the lncRNAs. However, such approaches are sensitive to the methods that are used to estimate the level of co-expression.

RESULTS: We have tested and compared two well-known statistical metrics (Pearson and Spearman) and two geometrical metrics (Sobolev and Fisher) for identification of the co-expressed genes, using experimental expression data across 19 normal human tissues. We have also used a benchmarking approach based on semantic similarity to evaluate how well these methods are able to predict annotation terms, using a well-annotated set of protein-coding genes.

CONCLUSION: This work shows that geometrical metrics, in particular in combination with the statistical metrics, will predict annotation terms more efficiently than traditional approaches. Tests on selected lncRNAs confirm that it is possible to predict the function of these genes given a reliable set of expression data. The software used for this investigation is freely available.}, } @article {pmid30567491, year = {2018}, author = {Ge, SX and Son, EW and Yao, R}, title = {iDEP: an integrated web application for differential expression and pathway analysis of RNA-Seq data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {534}, doi = {10.1186/s12859-018-2486-6}, pmid = {30567491}, issn = {1471-2105}, support = {IIA-1355423//National Science Foundation/ ; ACI-1548562//National Science Foundation/ ; GM083226//National Institute of General Medical Sciences/ ; }, mesh = {Animals ; B-Lymphocytes/cytology/metabolism ; Cell Proliferation ; Cells, Cultured ; Computational Biology/*methods ; Fibroblasts/cytology/metabolism ; *Gene Expression Profiling ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/*methods ; Homeodomain Proteins/antagonists & inhibitors ; Humans ; Lung/cytology/metabolism ; Mice ; RNA, Small Interfering/genetics ; Sequence Analysis, RNA/*methods ; *Software ; Transcription Factors/antagonists & inhibitors ; Transcriptome ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {BACKGROUND: RNA-seq is widely used for transcriptomic profiling, but the bioinformatics analysis of resultant data can be time-consuming and challenging, especially for biologists. We aim to streamline the bioinformatic analyses of gene-level data by developing a user-friendly, interactive web application for exploratory data analysis, differential expression, and pathway analysis.

RESULTS: iDEP (integrated Differential Expression and Pathway analysis) seamlessly connects 63 R/Bioconductor packages, 2 web services, and comprehensive annotation and pathway databases for 220 plant and animal species. The workflow can be reproduced by downloading customized R code and related pathway files. As an example, we analyzed an RNA-Seq dataset of lung fibroblasts with Hoxa1 knockdown and revealed the possible roles of SP1 and E2F1 and their target genes, including microRNAs, in blocking G1/S transition. In another example, our analysis shows that in mouse B cells without functional p53, ionizing radiation activates the MYC pathway and its downstream genes involved in cell proliferation, ribosome biogenesis, and non-coding RNA metabolism. In wildtype B cells, radiation induces p53-mediated apoptosis and DNA repair while suppressing the target genes of MYC and E2F1, and leads to growth and cell cycle arrest. iDEP helps unveil the multifaceted functions of p53 and the possible involvement of several microRNAs such as miR-92a, miR-504, and miR-30a. In both examples, we validated known molecular pathways and generated novel, testable hypotheses.

CONCLUSIONS: Combining comprehensive analytic functionalities with massive annotation databases, iDEP (http://ge-lab.org/idep/) enables biologists to easily translate transcriptomic and proteomic data into actionable insights.}, } @article {pmid30567489, year = {2018}, author = {Chen, L and Li, YX and Li, C and Shi, Y and Song, Y and Zhang, D and Li, Y and Wang, T}, title = {Genome-wide analysis of the pentatricopeptide repeat gene family in different maize genomes and its important role in kernel development.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {366}, doi = {10.1186/s12870-018-1572-2}, pmid = {30567489}, issn = {1471-2229}, support = {91735306//National Natural Science Foundation of China/ ; 91335206//National Natural Science Foundation of China/ ; 2014CB138200//Ministry of Science and Technology of the People's Republic of China/ ; 2013BAD01B02//Ministry of Science and Technology of the People's Republic of China/ ; 2017M620969//China Postdoctoral Science Foundation/ ; 2018NWB036-04//Ministry of Agriculture and Rural Affairs of the People's Republic of China/ ; }, abstract = {BACKGROUND: The pentatricopeptide repeat (PPR) gene family is one of the largest gene families in land plants (450 PPR genes in Arabidopsis, 477 PPR genes in rice and 486 PPR genes in foxtail millet) and is important for plant development and growth. Most PPR genes are encoded by plastid and mitochondrial genomes, and the gene products regulate the expression of the related genes in higher plants. However, the functions remain largely unknown, and systematic analysis and comparison of the PPR gene family in different maize genomes have not been performed.

RESULTS: In this study, systematic identification and comparison of PPR genes from two elite maize inbred lines, B73 and PH207, were performed. A total of 491 and 456 PPR genes were identified in the B73 and PH207 genomes, respectively. Basic bioinformatics analyses, including of the classification, gene structure, chromosomal location and conserved motifs, were conducted. Examination of PPR gene duplication showed that 12 and 15 segmental duplication gene pairs exist in the B73 and PH207 genomes, respectively, with eight duplication events being shared between the two genomes. Expression analysis suggested that 53 PPR genes exhibit qualitative variations in the different genetic backgrounds. Based on analysis of the correlation between PPR gene expression in kernels and kernel-related traits, four PPR genes are significantly negatively correlated with hundred kernel weight, 12 are significantly negatively correlated with kernel width, and eight are significantly correlated with kernel number. Eight of the 24 PPR genes are also located in metaQTL regions associated with yield and kernel-related traits in maize. Two important PPR genes (GRMZM2G353195 and GRMZM2G141202) might be regarded as important candidate genes associated with maize kernel-related traits.

CONCLUSIONS: Our results provide a more comprehensive understanding of PPR genes in different maize inbred lines and identify important candidate genes related to kernel development for subsequent functional validation in maize.}, } @article {pmid30567488, year = {2018}, author = {Cheng, Y and Li, H}, title = {Interspecies evolutionary divergence in Liriodendron, evidence from the nucleotide variations of LcDHN-like gene.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {195}, doi = {10.1186/s12862-018-1318-7}, pmid = {30567488}, issn = {1471-2148}, abstract = {BACKGROUND: Liriodendron is a genus of Magnoliaceae, which consists of two relict species, Liriodendron chinense and L. tulipifera. Although the morphologies are highly similar, the two species exhibit different adaptive capacity. Dehydrins (DHNs) are abiotic stresses resistant proteins in planta, which are associated with adaptive evolution. To better understand the evolution divergence between L. chinense and L. tulipifera and how DHN genes are associated with adaptation evolution, we firstly investigated the DNA polymorphisms of the LcDHN-like gene in 21 L. chinense and 6 L. tulipifera populations.

RESULTS: A 707 bp LcDHN-like gene was cloned, which included a 477 bp open reading frame (ORF) and coding 158 amino acids. 311 LcDHN-like gDNA sequences were obtained from 70 L. chinense and 35 L. tulipifera individuals. The AMOVA and phylogenetic relationship analysis showed significant differences between the two species. A higher genetic diversity was observed in L. tulipifera compared to L. chinense, in consistent with the higher adaptive capacity of L. tulipifera. Our data also suggested that the LcDHN-like genes' polymorphisms were under neutral mutation and purifying selection model in the L. chinense and L. tulipifera populations, respectively. The distinct expanding range and rate between the two species, haplotypes shared only in L.chinense's nearby populations, and wide dispersals in L. tulipifera could contribute to the obscure east-west separation in L. chinense and entirely unordered phylogeny in L. tulipifera. The completely separated nonsynonymous substitution at position 875 and the higher range scope of aliphatic index in L. tulipifera populations may be related with its higher adaptive capacity. Taken together, our study suggests LcDHN-like gene is a potential mark gene responsible for adaptive evolution divergence in Liriodendron.

CONCLUSIONS: Significant differences and completely distinct haplogroups between L. chinense and L. tulipifera showed that the two species have evolved into different directions. The more widely distribution, earlier haplogroups divergence events, and richer SNPs variations in L. tulipifera could imply its stronger adaptation in this species. And potential effect of the allelic variations in LcDHN-like gene may reflect the difference of water stress and chill tolerance between L. chinense and L. tulipifera, which could provide some information for further adaption evolution studies of Liriodendron.}, } @article {pmid30567486, year = {2018}, author = {Kahnt, B and Theodorou, P and Soro, A and Hollens-Kuhr, H and Kuhlmann, M and Pauw, A and Paxton, RJ}, title = {Small and genetically highly structured populations in a long-legged bee, Rediviva longimanus, as inferred by pooled RAD-seq.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {196}, doi = {10.1186/s12862-018-1313-z}, pmid = {30567486}, issn = {1471-2148}, abstract = {Adaptation to local host plants may impact a pollinator's population genetic structure by reducing gene flow and driving population genetic differentiation, representing an early stage of ecological speciation. South African Rediviva longimanus bees exhibit elongated forelegs, a bizarre adaptation for collecting oil from floral spurs of their Diascia hosts. Furthermore, R. longimanus foreleg length (FLL) differs significantly among populations, which has been hypothesised to result from selection imposed by inter-population variation in Diascia floral spur length. Here, we used a pooled restriction site-associated DNA sequencing (pooled RAD-seq) approach to investigate the population genetic structure of R. longimanus and to test if phenotypic differences in FLL translate into increased genetic differentiation (i) between R. longimanus populations and (ii) between phenotypes across populations. We also inferred the effects of demographic processes on population genetic structure and tested for genetic markers underpinning local adaptation. RESULTS: Populations showed marked genetic differentiation (average FST = 0.165), though differentiation was not statistically associated with differences between populations in FLL. All populations exhibited very low genetic diversity and were inferred to have gone through recent bottleneck events, suggesting extremely low effective population sizes. Genetic differentiation between samples pooled by leg length (short versus long) rather than by population of origin was even higher (FST = 0.260) than between populations, suggesting reduced interbreeding between long and short-legged individuals. Signatures of selection were detected in 1119 (3.8%) of a total of 29,721 SNP markers, CONCLUSIONS: Populations of R. longimanus appear to be small, bottlenecked and isolated. Though we could not detect the effect of local adaptation (FLL in response to floral spurs of host plants) on population genetic differentiation, short and long legged bees appeared to be partially differentiated, suggesting incipient ecological speciation. To test this hypothesis, greater resolution through the use of individual-based whole-genome analyses is now needed to quantify the degree of reproductive isolation between long and short legged bees between and even within populations.}, } @article {pmid30566652, year = {2018}, author = {Zhu, L and Gao, B and Yuan, S and Zhu, S}, title = {Scorpion toxins: positive selection at a distal site modulates functional evolution at a bioactive site.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy223}, pmid = {30566652}, issn = {1537-1719}, abstract = {The bioactive sites of proteins are those that directly interact with their targets. In many immunity- and predation-related proteins, they frequently experience positive selection for dealing with the changes of their targets from competitors. However, some sites that are far away from the interface between proteins and their targets are also identified to evolve under positive selection. Here, we explore the evolutionary implication of such a site in scorpion α-type toxins affecting sodium (Na+) channels (abbreviated as α-ScNaTxs) using a combination of experimental and computational approaches. We found that despite no direct involvement in interaction with Na+ channels, mutations at this site by different types of amino acids led to toxicity change on both rats and insects in three α-ScNaTxs, accompanying differential effects on their structures. Molecular dynamics simulations indicated that the mutations changed the conformational dynamics of the positively selected bioactive site-containing functional regions by allosteric communication, suggesting a potential evolutionary correlation between these bioactive sites and the distant non-bioactive site. Our results reveal for the first time the cause of fast evolution at non-bioactive sites of scorpion neurotoxins, which is presumably to adapt to the change of their bioactive sites through co-evolution to maintain an active conformation for channel binding. This might aid rational design of scorpion Na+ channel toxins with improved phyletic selectivity via modification of a distant non-bioactive site.}, } @article {pmid30566373, year = {2018}, author = {Ma, S and Meng, Z and Chen, R and Guan, KL}, title = {The Hippo Pathway: Biology and Pathophysiology.}, journal = {Annual review of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-biochem-013118-111829}, pmid = {30566373}, issn = {1545-4509}, abstract = {The Hippo pathway was initially discovered in Drosophila melanogaster as a key regulator of tissue growth. It is an evolutionarily conserved signaling cascade regulating numerous biological processes, including cell growth and fate decision, organ size control, and regeneration. The core of the Hippo pathway in mammals consists of a kinase cascade, MST1/2 and LATS1/2, as well as downstream effectors, transcriptional coactivators YAP and TAZ. These core components of the Hippo pathway control transcription programs involved in cell proliferation, survival, mobility, stemness, and differentiation. The Hippo pathway is tightly regulated by both intrinsic and extrinsic signals, such as mechanical force, cell-cell contact, polarity, energy status, stress, and many diffusible hormonal factors, the majority of which act through G protein-coupled receptors. Here, we review the current understanding of molecular mechanisms by which signals regulate the Hippo pathway with an emphasis on mechanotransduction and the effects of this pathway on basic biology and human diseases Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30566372, year = {2018}, author = {Baßler, J and Hurt, E}, title = {Eukaryotic Ribosome Assembly.}, journal = {Annual review of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-biochem-013118-110817}, pmid = {30566372}, issn = {1545-4509}, abstract = {Ribosomes, which synthesize the proteins of a cell, comprise ribosomalRNA and ribosomal proteins, which coassemble hierarchically during a process termed ribosome biogenesis. Historically, biochemical and molecular biology approaches have revealed how preribosomal particles form and mature in consecutive steps, starting in the nucleolus and terminating after nuclear export into the cytoplasm. However, only recently, due to the revolution in cryo-electron microscopy, could pseudoatomic structures of different preribosomal particles be obtained. Together with in vitro maturation assays, these findings shed light on how nascent ribosomes progress stepwise along a dynamic biogenesis pathway. Preribosomes assemble gradually, chaperoned by a myriad of assembly factors and small nucleolar RNAs, before they reach maturity and enter translation. This information will lead to a better understanding of how ribosome synthesis is linked to other cellular pathways in humans and how it can cause diseases, including cancer, if disturbed. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30566074, year = {2018}, author = {Kang, JY and Kim, MJ and Chun, J and Son, KP and Jahng, KY}, title = {Marinobacterium boryeongense sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003184}, pmid = {30566074}, issn = {1466-5034}, abstract = {A Gram-stain-negative and strictly aerobic bacterium, designated DMHB-2T, was isolated from a sample of seawater collected off the Yellow Sea coast of the Republic of Korea. Cells were short rods and motile by means of a single polar flagellum. Catalase and oxidase activities were positive. Growth occurred at pH 5.5-10.0 (optimum, pH 6.0), 15-45 °C (optimum, 25 °C) and with 1-9 % NaCl (optimum, 3 %). The respiratory quinone was ubiquinone-8 and the major fatty acids were C16 : 0 (17.9 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c; 26.1 %) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 37.4 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain DMHB-2T belong to the genus Marinobacterium, with the highest 16S rRNA gene sequence similarity of 95.2 % to Marinobacterium zhoushanense KCTC 42782T. The genomic DNA G+C content of strain DMHB-2T was 60.8 mol%. On the basis of the phenotypic, chemotaxonomic and genotypic characteristics presented in this study, strain DMHB-2T is suggested to represent a novel species of the genus Marinobacterium, for which the name Marinobacteriumboryeongense sp. nov. is proposed. The type strain is DMHB-2T (=KACC 19225T=JCM 31902T).}, } @article {pmid30566073, year = {2018}, author = {Song, L and Liu, H and Cai, S and Zhou, Y}, title = {Marinimicrobium alkaliphilum sp. nov., an alkaliphilic bacterium isolated from soil and emended description of the genus Marinimicrobium.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003183}, pmid = {30566073}, issn = {1466-5034}, abstract = {Two Gram-stain-negative, rod-shaped bacterial strains, designated SW121T and W12, were isolated from a soil sample collected from Shanxi Province, China. The two strains were strictly aerobic, catalase-positive and oxidase-positive. Both strains grew at 6-42 °C (optimum, 30 °C), at pH 5.5-11.0 (optimum, pH 9.0) and in the presence of 0-15.0 % (w/v) NaCl (optimum, 2.0-3.0 %). The predominant cellular fatty acids of strain SW121T were C16 : 0, C18 : 1ω7c and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). Strain SW121T contained ubiquinone-8 as the sole respiratory quinone. Diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol were major polar lipids. The genomic DNA G+C content of strain SW121T was 58.5 mol%. Comparative analysis of 16S rRNA gene sequences revealed that strains SW121T and W12 showed the highest similarities to Marinimicrobium koreense DSM 16974T(95.7 and 95.5 %, respectively). On the basis of phylogenetic inference and phenotypic characteristics, it is proposed that the two strains represent a novel species of the genus Marinimicrobium, for which the name Marinimicrobiumalkaliphilum sp. nov. is proposed. The type strain is SW121T (=CGMCC 1.16166T=KCTC 62651T).}, } @article {pmid30566071, year = {2018}, author = {Joung, Y and Jang, HJ and Song, J and Cho, JC}, title = {Flavobacterium hydrophilum sp. nov. and Flavobacterium cheongpyeongense sp. nov., isolated from freshwater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003083}, pmid = {30566071}, issn = {1466-5034}, abstract = {Two Gram-stain-negative, non-motile, yellow-pigmented bacterial strains, designated IMCC34758T and IMCC34759T, were isolated from freshwater. Phylogenetic analysis based on 16S rRNA gene sequences showed that the two strains formed a distinct clade within the genus Flavobacterium and they shared 97.9 % sequence similarity. The average nucleotide identity (ANI) and digital DNA-DNA hybridization values (dDDH) between the two strains were 85.5 and 30.2 %, respectively, indicating that they are separate species. The two strains showed ≤98.5 % 16S rRNA gene sequence similarities, 80.6-81.3 % of ANI and 24.7-25.1 % of dDDH values to closely related species of the genus Flavobacterium, indicating that the two strains each represent novel Flavobacteriumspecies. The respiratory quinone detected in both strains was menaquinone-6 (MK-6). The major polar lipids of the two strains were phosphatidylethanolamine, an unidentified aminolipid, an unidentified aminophospholipid and an unidentified polar lipid. The DNA G+C contents of strains IMCC34758T and IMCC34759T were 34.0 and 34.1 mol%, respectively. The major fatty acids of the two strains were very similar to each other, comprising iso-C15 : 0, iso-C15 : 1 G, anteiso-C15 : 0 and summed feature 3 (C16 : 1 ω6c and/or C16 : 1 ω7c). Phenotypic characteristics including enzyme activities and carbon source utilization differentiated the two strains from other Flavobacteriumspecies. Based on these results, strains IMCC34758T and IMCC34759T were considered to represent novel species in the genus Flavobacterium, for which the names Flavobacterium hydrophilum (IMCC34758T=KACC 19591T=NBRC 113423T) and Flavobacterium cheongpyeongense (IMCC34759T=KACC 19592T=NBRC 113424T) are proposed, respectively.}, } @article {pmid30566070, year = {2018}, author = {Song, Z and Song, Y and Yu, Y and Choi, L and Wang, G and Li, M}, title = {Dyadobacter luticola sp. nov., isolated from a sewage sediment sample.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003178}, pmid = {30566070}, issn = {1466-5034}, abstract = {A Gram-stain-negative, non-motile, aerobic bacterial strain, designated T17T was isolated from a sample of sewage sediment from a Busan park (Republic of Korea). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain T17T had the highest 16S rRNA gene sequence similarity to Dyadobacter soli KCTC 22481T (97.3 %), Dyadobacter fermentans DSM 18053T (97.1 %) and Dyadobacter sediminis CGMCC 1.12895T (97.1 %). The isolate exhibited relatively low levels of DNA-DNA relatedness with respect to D. soli KCTC 22481T(28.2±3.6 %). The DNA G+C content was 49.1 mol%. The unique respiratory quinone was MK-7 and the major polar lipids were phosphatidylethanolamine, five unidentified lipids, four aminolipids, two unidentified phospholipids and one glycophospholipid. The predominant cellular fatty acids (>5 % of total) were summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH; 44.3 %), iso-C15 : 0 (15.7 %), C16 : 1ω5c (9.6 %), iso-C17 : 0 3-OH (9.3 %) and C16 : 0 (5.6 %). Moreover, physiological and biochemical characteristics distinguished strain T17T from its related species, including temperature and pH ranges for growth, being positive for acetate hydrolysis, and being negative for acid produced from melibiose and rhamnose. The genotypic, chemotaxonomic and phenotypic data revealed that strain T17T represents a novel species of the genus Dyadobacter, for which the name Dyadobacterluticola sp. nov. is proposed. The type strain is T17T (=KCTC 52981T=CCTCC AB 2017091T).}, } @article {pmid30566068, year = {2018}, author = {Qin, J and Hu, Y and Feng, Y and Xaioju, L and Zong, Z}, title = {Pseudomonas sichuanensis sp. nov., isolated from hospital sewage.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003188}, pmid = {30566068}, issn = {1466-5034}, abstract = {A bacterial strain, designated WCHPs060039T, was isolated from hospital sewage in China. The strain was Gram-stain-negative, obligate aerobic, flagellum-motile and positive for oxidase and catalase. A preliminary analysis of the 16S rRNA gene sequences indicated that strain WCHPs060039T belonged to the genus Pseudomonasand was closely related to members of the Pseudomonas putida group, with the highest similarities to Pseudomonas entomophila L48T (99.5 %), Pseudomonas mosselii CIP 105259T (99.52 %), Pseudomonas taiwanensis BCRC 17751T (99.45 %) and Pseudomonas plecoglossicida NBRC 103162T (99.31 %). Whole genome sequencing of the strain was performed. Phylogenetic analysis based on a set of core gene sequences revealed that the strain was distinct from its closest Pseudomonas species. Average nucleotide identity based on blast and in silico DNA-DNA hybridizationrevealed low genome relatedness to its closest Pseudomonas species (below the recommended thresholds of 95 and 70 %, respectively, for species delineation). The major fatty acids of the strain were 16:0, 17:0 cyclo, summed feature 3 (16:1ω7c/16:1ω6c and 16:1ω6c/16:1ω7c) and summed feature 8 (18:1ω7c). The ability to utilize inositol, sorbitol and d-glucuronic acid could differentiate strain WCHPs060039T from the closely related Pseudomonas species. It is therefore evident that strain WCHPs060039T represents a novel species of the genus Pseudomonas, for which the name Pseudomonassichuanensissp. nov. is proposed. The type strain is WCHPs060039T (GDMCC 1.1424T=CNCTC 7662T).}, } @article {pmid30565827, year = {2018}, author = {He, X and Chadwick, G and Kempes, C and Shi, Y and McGlynn, S and Orphan, V and Meile, C}, title = {Microbial interactions in the anaerobic oxidation of methane: model simulations constrained by process rates and activity patterns.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14507}, pmid = {30565827}, issn = {1462-2920}, support = {DE-SC0016469//Biological and Environmental Research/ ; //Genomic Sciences Program in the DOE Office of Science/ ; }, abstract = {Proposed syntrophic interactions between the archaeal and bacterial cells mediating anaerobic oxidation of methane coupled with sulfate reduction include electron transfer through (1) the exchange of H2 or small organic molecules between methane-oxidizing archaea and sulfate-reducing bacteria, (2) the delivery of disulfide from methane-oxidizing archaea to bacteria for disproportionation and (3) direct interspecies electron transfer. Each of these mechanisms was implemented in a reactive transport model. The simulated activities across different arrangements of archaeal and bacterial cells and aggregate sizes were compared to empirical data for AOM rates and intra-aggregate spatial patterns of cell-specific anabolic activity determined by FISH-nanoSIMS. Simulation results showed that rates for chemical diffusion by mechanism (1) were limited by the build-up of metabolites, while mechanisms (2) and (3) yielded cell specific rates and archaeal activity distributions that were consistent with observations from single cell resolved FISH-nanoSIMS analyses. The novel integration of both intra-aggregate and environmental data provided powerful constraints on the model results, but the similarities in model outcomes for mechanisms (2) and (3) highlight the need for additional observational data (e.g. genomic or physiological) on electron transfer and metabolic functioning of these globally important methanotrophic consortia.}, } @article {pmid30565818, year = {2018}, author = {Zhang, H and Yoshizawa, S and Sun, Y and Huang, Y and Chu, X and González, JM and Pinhassi, J and Luo, H}, title = {Repeated evolutionary transitions of flavobacteria from marine to non-marine habitats.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14509}, pmid = {30565818}, issn = {1462-2920}, support = {AoE/M-403/16//Hong Kong Research Grants Council Area of Excellence Scheme/ ; 4930062//Chinese University of Hong Kong/ ; //Swedish Research Council FORMAS/ ; CTM2016-80095-C2-2-R//Spanish Ministry of Science and Innovation/ ; }, abstract = {The taxonomy of marine and non-marine organisms rarely overlap, but the mechanisms underlying this distinction are often unknown. Here, we predicted three major ocean-to-land transitions in the evolutionary history of Flavobacteriaceae, a family known for polysaccharide and peptide degradation. These unidirectional transitions were associated with repeated losses of marine signature genes and repeated gains of non-marine adaptive genes. This included various Na+ -dependent transporters, osmolyte transporters and glycoside hydrolases (GH) for sulfated polysaccharide utilization in marine descendants, and in non-marine descendants genes for utilizing the land plant material pectin and genes facilitating terrestrial host interactions. The K+ scavenging ATPase was repeatedly gained whereas the corresponding low-affinity transporter repeatedly lost upon transitions, reflecting K+ ions are less available to non-marine bacteria. Strikingly, the central metabolism Na+ -translocating NADH: quinone dehydrogenase gene was repeatedly gained in marine descendants, whereas the H+ -translocating counterpart was repeatedly gained in non-marine lineages. Furthermore, GH genes were depleted in isolates colonizing animal hosts but abundant in bacteria inhabiting other non-marine niches; thus relative abundances of GH versus peptidase genes among Flavobacteriaceae lineages were inconsistent with the marine versus non-marine dichotomy. We suggest that phylogenomic analyses can cast novel light on mechanisms explaining the distribution and ecology of key microbiome components.}, } @article {pmid30565370, year = {2018}, author = {Nimmo, DG and Avitabile, S and Banks, SC and Bliege Bird, R and Callister, K and Clarke, MF and Dickman, CR and Doherty, TS and Driscoll, DA and Greenville, AC and Haslem, A and Kelly, LT and Kenny, SA and Lahoz-Monfort, JJ and Lee, C and Leonard, S and Moore, H and Newsome, TM and Parr, CL and Ritchie, EG and Schneider, K and Turner, JM and Watson, S and Westbrooke, M and Wouters, M and White, M and Bennett, AF}, title = {Animal movements in fire-prone landscapes.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12486}, pmid = {30565370}, issn = {1469-185X}, support = {DE170101466//Australian Research Council/ ; Mallee Hawkeye Project//Victorian Department of Land, Water and Planning/ ; //LaTrobe University and Deakin University/ ; //Department of Land, Water and Planning as part of the Mallee Hawkeye Project/ ; }, abstract = {Movement is a trait of fundamental importance in ecosystems subject to frequent disturbances, such as fire-prone ecosystems. Despite this, the role of movement in facilitating responses to fire has received little attention. Herein, we consider how animal movement interacts with fire history to shape species distributions. We consider how fire affects movement between habitat patches of differing fire histories that occur across a range of spatial and temporal scales, from daily foraging bouts to infrequent dispersal events, and annual migrations. We review animal movements in response to the immediate and abrupt impacts of fire, and the longer-term successional changes that fires set in train. We discuss how the novel threats of altered fire regimes, landscape fragmentation, and invasive species result in suboptimal movements that drive populations downwards. We then outline the types of data needed to study animal movements in relation to fire and novel threats, to hasten the integration of movement ecology and fire ecology. We conclude by outlining a research agenda for the integration of movement ecology and fire ecology by identifying key research questions that emerge from our synthesis of animal movements in fire-prone ecosystems.}, } @article {pmid30565005, year = {2018}, author = {Zlotina, A and Maslova, A and Kosyakova, N and Al-Rikabi, ABH and Liehr, T and Krasikova, A}, title = {Heterochromatic regions in Japanese quail chromosomes: comprehensive molecular-cytogenetic characterization and 3D mapping in interphase nucleus.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9597-9}, pmid = {30565005}, issn = {1573-6849}, support = {MK-1630.2017.4//Grant of the President of the Russian Federation/ ; }, abstract = {Chromosomes of Japanese quail (Coturnix coturnix japonica, 2n=78), a galliform domestic species closely related to chicken, possess multiple heterochromatic segments. Due to the difficulties in careful analysis of such heterochromatic regions, there is a lack of data on their DNA composition, epigenetic status, as well as spatial distribution in interphase nucleus. In the present study, we applied giant lampbrush chromosome (LBC) microdissection for high-resolution analysis of quail centromeric regions of macrochromosomes and polymorphic short arms of submetacentric microchromosomes. FISH with the dissected material on mitotic and meiotic chromosomes indicated that in contrast to centromeres of chicken macrochromosomes, which are known to harbor chromosome-specific and, in some cases, tandem repeat-free sequences, centromeres of quail macroautosomes (CCO1-CCO11) have canonical organization. CCO1-CCO11 centromeres possess massive blocks of common DNA repeats demonstrating transcriptional activity at LBC stage. These repeats seem to have been subjected to chromosome size-correlated homogenization previously described primarily for avian microchromosomes. In addition, comparative FISH on chicken chromosomes supported the previous data on centromere repositioning events during galliform karyotype evolution. In interphase nucleus of different cell types, repetitive elements specific for microchromosome short arms constitute the material of prominent centrally located chromocenters enriched with markers of constitutive heterochromatin and rimmed with clusters of microchromosomal centromeric BglII-repeat. Thus, clustering of such repeats is responsible for the peculiar architecture of quail interphase nucleus. In contrast, centromere repeats of the largest macrochromosomes (CCO1 and CCO2) are predominantly localized in perinuclear heterochromatin. The possible involvement of the isolated repeats in radial genome organization is discussed.}, } @article {pmid30564885, year = {2018}, author = {Zhang, W and Zhou, X and Yuan, Y and Liu, B and Epstein, SS and He, S}, title = {Complete Genome Sequence of Saccharospirillum mangrovi HK-33T Sheds Light on the Ecological Role of a Bacterium in Mangrove Sediment Environment.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1600-3}, pmid = {30564885}, issn = {1432-0991}, support = {LQ18C010001//Natural Science Foundation of Zhejiang Province/ ; 41776168//National Natural Science Foundation of China/ ; NBHY-2017-P2//Ningbo Public Service Platform for High-Value Utilization of Marine Biological Resources/ ; }, abstract = {We present the genome sequence of Saccharospirillum mangrovi HK-33T, isolated from a mangrove sediment sample in Haikou, China. The complete genome of S. mangrovi HK-33T consisted of a single-circular chromosome with the size of 3,686,911 bp as well as an average G + C content of 57.37%, and contained 3,383 protein-coding genes, 4 operons of 16S-23S-5S rRNA genes, and 52 tRNA genes. Genomic annotation indicated that the genome of S. mangrovi HK-33T had many genes related to oligosaccharide and polysaccharide degradation and utilization of polyhydroxyalkanoate. For nitrogen cycle, genes encoding nitrate and nitrite reductase, glutamate dehydrogenase, glutamate synthase, and glutamine synthetase could be found. For phosphorus cycle, genes related to polyphosphate kinases (ppk1 and ppk2), the high-affinity phosphate-specific transport (Pst) system, and the low-affinity inorganic phosphate transporter (pitA) were predicted. For sulfur cycle, cysteine synthase and type III acyl coenzyme A transferase (dddD) coding genes were searched out. This study provides evidence about carbon, nitrogen, phosphorus, and sulfur metabolic patterns of S. mangrovi HK-33T and broadens our understandings about ecological roles of this bacterium in the mangrove sediment environment.}, } @article {pmid30564861, year = {2019}, author = {Whittington, AC and Rokyta, DR}, title = {Biophysical Spandrels form a Hot-Spot for Kosmotropic Mutations in Bacteriophage Thermal Adaptation.}, journal = {Journal of molecular evolution}, volume = {87}, number = {1}, pages = {27-36}, doi = {10.1007/s00239-018-9882-4}, pmid = {30564861}, issn = {1432-1432}, support = {R01 GM-099723//National Institutes of Health/ ; R01 GM099723/GM/NIGMS NIH HHS/United States ; }, abstract = {Temperature plays a dominating role in protein structure and function, and life has evolved myriad strategies to adapt proteins to environmental thermal stress. Cellular systems can utilize kosmotropic osmolytes, the products of complex biochemical pathways, to act as chemical chaperones. These extrinsic molecules, e.g., trehalose, alter local water structure to modulate the strength of the hydrophobic effect and increase protein stability. In contrast, simpler genetic systems must rely on intrinsic mutation to affect protein stability. In naturally occurring microvirid bacteriophages of the subfamily Bullavirinae, capsid stability is randomly distributed across the phylogeny, suggesting it is not phylogenetically linked and could be altered through adaptive mutation. We hypothesized that these phages could utilize an adaptive mechanism that mimics the stabilizing effects of the kosmotrope trehalose through mutation. Kinetic stability of wild-type ID8, a relative of ΦX174, displays a saturable response to trehalose. Thermal adaptation mutations in ID8 improve capsid stability and reduce responsiveness to trehalose suggesting the mutations move stability closer to the kosmotropic saturation point, mimicking the kosmotropic effect of trehalose. These mutations localize to and modulate the hydrophobicity of a cavern formation at the interface of phage coat and spike proteins-an evolutionary spandrel. Across a series of genetically distinct phages, responsiveness to trehalose correlates positively with cavern hydrophobicity suggesting that the level of hydrophobicity of the cavern may provide a biophysical gating mechanism constraining or permitting adaptation in a lineage-specific manner. Our results demonstrate that a single mutation can exploit pre-existing, non-adaptive structural features to mimic the adaptive effects of complex biochemical pathways.}, } @article {pmid30563976, year = {2018}, author = {Gibney, E and Callaway, E and Cyranoski, D and Gaind, N and Tollefson, J and Courtland, R and Law, YH and Maher, B and Else, H and Castelvecchi, D}, title = {Nature's 10: Ten people who mattered in science in 2018.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {325-335}, doi = {10.1038/d41586-018-07683-5}, pmid = {30563976}, issn = {1476-4687}, } @article {pmid30563975, year = {2018}, author = {Tollefson, J}, title = {Massive ocean carbon sink spotted burping CO2 on the sly.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {311-312}, doi = {10.1038/d41586-018-07784-1}, pmid = {30563975}, issn = {1476-4687}, } @article {pmid30563974, year = {2018}, author = {Cyranoski, D}, title = {China introduces 'social' punishments for scientific misconduct.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {312}, doi = {10.1038/d41586-018-07740-z}, pmid = {30563974}, issn = {1476-4687}, } @article {pmid30563973, year = {2018}, author = {Guglielmi, G}, title = {Italian scientists protest funding for vaccine-safety investigation.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {310-311}, doi = {10.1038/d41586-018-07464-0}, pmid = {30563973}, issn = {1476-4687}, } @article {pmid30563972, year = {2018}, author = {Zastrow, M}, title = {South Korean scientists protest treatment of university president accused of misusing funds.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {309-310}, doi = {10.1038/d41586-018-07742-x}, pmid = {30563972}, issn = {1476-4687}, } @article {pmid30563858, year = {2019}, author = {Soe, CMM and Nagabhushana, GP and Shivaramaiah, R and Tsai, H and Nie, W and Blancon, JC and Melkonyan, F and Cao, DH and Traoré, B and Pedesseau, L and Kepenekian, M and Katan, C and Even, J and Marks, TJ and Navrotsky, A and Mohite, AD and Stoumpos, CC and Kanatzidis, MG}, title = {Structural and thermodynamic limits of layer thickness in 2D halide perovskites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {58-66}, doi = {10.1073/pnas.1811006115}, pmid = {30563858}, issn = {1091-6490}, abstract = {In the fast-evolving field of halide perovskite semiconductors, the 2D perovskites (A')2(A) n-1M n X3n+1 [where A = Cs+, CH3NH3+, HC(NH2)2+; A' = ammonium cation acting as spacer; M = Ge2+, Sn2+, Pb2+; and X = Cl-, Br-, I-] have recently made a critical entry. The n value defines the thickness of the 2D layers, which controls the optical and electronic properties. The 2D perovskites have demonstrated preliminary optoelectronic device lifetime superior to their 3D counterparts. They have also attracted fundamental interest as solution-processed quantum wells with structural and physical properties tunable via chemical composition, notably by the n value defining the perovskite layer thickness. The higher members (n > 5) have not been documented, and there are important scientific questions underlying fundamental limits for n To develop and utilize these materials in technology, it is imperative to understand their thermodynamic stability, fundamental synthetic limitations, and the derived structure-function relationships. We report the effective synthesis of the highest iodide n-members yet, namely (CH3(CH2)2NH3)2(CH3NH3)5Pb6I19 (n = 6) and (CH3(CH2)2NH3)2(CH3NH3)6Pb7I22 (n = 7), and confirm the crystal structure with single-crystal X-ray diffraction, and provide indirect evidence for "(CH3(CH2)2NH3)2(CH3NH3)8Pb9I28" ("n = 9"). Direct HCl solution calorimetric measurements show the compounds with n > 7 have unfavorable enthalpies of formation (ΔHf), suggesting the formation of higher homologs to be challenging. Finally, we report preliminary n-dependent solar cell efficiency in the range of 9-12.6% in these higher n-members, highlighting the strong promise of these materials for high-performance devices.}, } @article {pmid30563857, year = {2019}, author = {Murakawa, T and Baba, S and Kawano, Y and Hayashi, H and Yano, T and Kumasaka, T and Yamamoto, M and Tanizawa, K and Okajima, T}, title = {In crystallo thermodynamic analysis of conformational change of the topaquinone cofactor in bacterial copper amine oxidase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {135-140}, doi = {10.1073/pnas.1811837116}, pmid = {30563857}, issn = {1091-6490}, abstract = {In the catalytic reaction of copper amine oxidase, the protein-derived redox cofactor topaquinone (TPQ) is reduced by an amine substrate to an aminoresorcinol form (TPQamr), which is in equilibrium with a semiquinone radical (TPQsq). The transition from TPQamr to TPQsq is an endothermic process, accompanied by a significant conformational change of the cofactor. We employed the humid air and glue-coating (HAG) method to capture the equilibrium mixture of TPQamr and TPQsq in noncryocooled crystals of the enzyme from Arthrobacter globiformis and found that the equilibrium shifts more toward TPQsq in crystals than in solution. Thermodynamic analyses of the temperature-dependent equilibrium also revealed that the transition to TPQsq is entropy-driven both in crystals and in solution, giving the thermodynamic parameters that led to experimental determination of the crystal packing effect. Furthermore, we demonstrate that the binding of product aldehyde to the hydrophobic pocket in the active site produces various equilibrium states among two forms of the product Schiff-base, TPQamr, and TPQsq, in a pH-dependent manner. The temperature-controlled HAG method provides a technique for thermodynamic analysis of conformational changes occurring in protein crystals that are hardly scrutinized by conventional cryogenic X-ray crystallography.}, } @article {pmid30563856, year = {2019}, author = {de Boer, L and Axelsson, J and Chowdhury, R and Riklund, K and Dolan, RJ and Nyberg, L and Bäckman, L and Guitart-Masip, M}, title = {Dorsal striatal dopamine D1 receptor availability predicts an instrumental bias in action learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {261-270}, doi = {10.1073/pnas.1816704116}, pmid = {30563856}, issn = {1091-6490}, abstract = {Learning to act to obtain reward and inhibit to avoid punishment is easier compared with learning the opposite contingencies. This coupling of action and valence is often thought of as a Pavlovian bias, although recent research has shown it may also emerge through instrumental mechanisms. We measured this learning bias with a rewarded go/no-go task in 60 adults of different ages. Using computational modeling, we characterized the bias as being instrumental. To assess the role of endogenous dopamine (DA) in the expression of this bias, we quantified DA D1 receptor availability using positron emission tomography (PET) with the radioligand [11C]SCH23390. Using principal-component analysis on the binding potentials in a number of cortical and striatal regions of interest, we demonstrated that cortical, dorsal striatal, and ventral striatal areas provide independent sources of variance in DA D1 receptor availability. Interindividual variation in the dorsal striatal component was related to the strength of the instrumental bias during learning. These data suggest at least three anatomical sources of variance in DA D1 receptor availability separable using PET in humans, and we provide evidence that human dorsal striatal DA D1 receptors are involved in the modulation of instrumental learning biases.}, } @article {pmid30563855, year = {2019}, author = {McElroy, GS and Chandel, NS}, title = {Probing mitochondrial metabolism in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {20-22}, doi = {10.1073/pnas.1819614116}, pmid = {30563855}, issn = {1091-6490}, } @article {pmid30563854, year = {2019}, author = {Feiner, R and Dvir, T}, title = {A ray of light for treating cardiac conduction disorders.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {347-349}, doi = {10.1073/pnas.1819948116}, pmid = {30563854}, issn = {1091-6490}, } @article {pmid30563853, year = {2019}, author = {Pang, TY and Lercher, MJ}, title = {Each of 3,323 metabolic innovations in the evolution of E. coli arose through the horizontal transfer of a single DNA segment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {187-192}, doi = {10.1073/pnas.1718997115}, pmid = {30563853}, issn = {1091-6490}, abstract = {Even closely related prokaryotes often show an astounding diversity in their ability to grow in different nutritional environments. It has been hypothesized that complex metabolic adaptations-those requiring the independent acquisition of multiple new genes-can evolve via selectively neutral intermediates. However, it is unclear whether this neutral exploration of phenotype space occurs in nature, or what fraction of metabolic adaptations is indeed complex. Here, we reconstruct metabolic models for the ancestors of a phylogeny of 53 Escherichia coli strains, linking genotypes to phenotypes on a genome-wide, macroevolutionary scale. Based on the ancestral and extant metabolic models, we identify 3,323 phenotypic innovations in the history of the E. coli clade that arose through changes in accessory genome content. Of these innovations, 1,998 allow growth in previously inaccessible environments, while 1,325 increase biomass yield. Strikingly, every observed innovation arose through the horizontal acquisition of a single DNA segment less than 30 kb long. Although we found no evidence for the contribution of selectively neutral processes, 10.6% of metabolic innovations were facilitated by horizontal gene transfers on earlier phylogenetic branches, consistent with a stepwise adaptation to successive environments. Ninety-eight percent of metabolic phenotypes accessible to the combined E. coli pangenome can be bestowed on any individual strain by transferring a single DNA segment from one of the extant strains. These results demonstrate an amazing ability of the E. coli lineage to adapt to novel environments through single horizontal gene transfers (followed by regulatory adaptations), an ability likely mirrored in other clades of generalist bacteria.}, } @article {pmid30563780, year = {2018}, author = {Markus, MB}, title = {Plasmodium: Yet More Don'ts.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.006}, pmid = {30563780}, issn = {1471-5007}, } @article {pmid30563727, year = {2018}, author = {Quatrini, R and Johnson, DB}, title = {Acidithiobacillus ferrooxidans.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.11.009}, pmid = {30563727}, issn = {1878-4380}, abstract = {Acidithiobacillus ferrooxidans is by far the most widely studied of all extremely acidophilic prokaryotes. While it is found in many types of natural low-pH environments in a variety of geoclimatic contexts, it has been more widely cited in anthropogenic (mostly mine-impacted) environments. It is responsible for accelerating the oxidative dissolution of sulfide minerals, causing the generation of polluting acidic metal-rich drainage waters but also facilitating the recovery of base and precious metals from mineral leachates. It can colonize barren mineral landscapes, is a driver of ecological successions in acidic biotopes, and is an important model organism in astrobiology. It catalyses the dissimilatory oxidation of iron, sulfur, and hydrogen, and the reduction of iron and sulfur, and has a major impact in the geochemical cycling of these elements in low-pH environments. This infographic summarizes the fundamental phylogeny, physiology and genomic features of this extremophile.}, } @article {pmid30563726, year = {2019}, author = {Kufel, J and Grzechnik, P}, title = {Small Nucleolar RNAs Tell a Different Tale.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {104-117}, doi = {10.1016/j.tig.2018.11.005}, pmid = {30563726}, issn = {0168-9525}, abstract = {Transcribing RNA Polymerase II interacts with multiple factors that orchestrate maturation and stabilisation of messenger RNA. For the majority of noncoding RNAs, the polymerase complex employs entirely different strategies, which usually direct the nascent transcript to ribonucleolytic degradation. However, some noncoding RNA classes use endo- and exonucleases to achieve functionality. Here we review processing of small nucleolar RNAs that are transcribed by RNA Polymerase II as precursors, and whose 5' and 3' ends undergo processing to release mature, functional molecules. The maturation strategies of these noncoding RNAs in various organisms follow a similar pattern but employ different factors and are strictly correlated with genomic organisation of their genes.}, } @article {pmid30563648, year = {2018}, author = {Prünster, MM and Ricci, L and Brown, FD and Tiozzo, S}, title = {De novo neurogenesis in a budding chordate: Co-option of larval anteroposterior patterning genes in a transitory neurogenic organ.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.10.009}, pmid = {30563648}, issn = {1095-564X}, abstract = {During metamorphosis of solitary ascidians, part of the larval tubular nervous system is recruited to form the adult central nervous system (CNS) through neural stem-like cells called ependymal cells. The anteroposterior (AP) gene expression patterning of the larval CNS regionalize the distribution of the ependymal cells, which contains the positional information of the neurons of the adult nervous system. In colonial ascidians, the CNS of asexually developed zooids has the same morphology of the one of the post-metamorphic zooids. However, its development follows a completely different organogenesis that lacks embryogenesis, a larval phase and metamorphosis. In order to describe neurogenesis during asexual development (blastogenesis), we followed the expression of six CNS AP patterning genes conserved in chordates and five neural-related genes to determine neural cell identity in Botryllus schlosseri. We observed that a neurogenesis occurs de novo on each blastogenic cycle starting from a neurogenic transitory structure, the dorsal tube. The dorsal tube partially co-opts the AP patterning of the larval CNS markers, and potentially combine the neurogenesis role and provider of positional clues for neuron patterning. This study shows how a larval developmental module is reused in a direct asexual development in order to generate the same structures.}, } @article {pmid30563564, year = {2018}, author = {Wijekoon Mudiyanselage, KW and Samkange-Zeeb, F and Brand, T and Zeeb, H}, title = {Exploring ethnic differences in understanding of self-rated health among persons of Turkish, Bosnian and German origin.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {903}, doi = {10.1186/s13104-018-4019-9}, pmid = {30563564}, issn = {1756-0500}, abstract = {OBJECTIVE: Self-rated health (SRH) is a widely used indictor of the subjective health status in population-based studies. However, differences in the reporting style across ethnic groups may limit the predictive ability of SRH for objective health outcomes. As part of the preparation phase of the UPWEB (understanding the practice and developing the concept of welfare bricolage) project, this study explored ethnic differences in the understanding of self-rated health among persons of Turkish, Bosnian and German origin, living in two northern Germany cities, Bremen and Hamburg.

RESULTS: Thirty persons, 10 per ethnic group, aged 32-82 years, took part in the assessment based on cognitive interviewing. All three ethnic groups defined SRH as the absence or presence of visible or non-visible disturbances and/or deviations from the norm, the ability or limited ability to act as well as the result of specific behaviours. However, only participants from the two migrant groups referred to community cohesion and religious or traditional beliefs as aspects of their SRH, indicating a systematic difference in the understanding of this question.}, } @article {pmid30563558, year = {2018}, author = {Amaha, ND and Berhe, YH and Kaushik, A}, title = {Assessment of inpatient antibiotic use in Halibet National Referral Hospital using WHO indicators: a retrospective study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {904}, doi = {10.1186/s13104-018-4000-7}, pmid = {30563558}, issn = {1756-0500}, abstract = {OBJECTIVE: Inappropriate use of antibiotics in primary care and hospital settings is a major contributing factor to the spread of antibiotic resistance. Many microorganisms were tested in Eritrea and have proven resistant to ampicillin. The aim of this study was to investigate the prescription pattern, hospital indicator and patient care indicator of antibiotics among hospitalized patients in Halibet National Referral Hospital, Asmara, Eritrea.

RESULTS: The data on prescription patterns showed 79% of hospitalizations had at least one antibiotic prescribed and on average 1.29 antibiotics were prescribed per hospitalization; prescribing using generic name was at 97%; all (100%) of the antibiotics were prescribed from the Eritrean National List of Medicines. On average an antibiotic was prescribed for 6.36 days (SD = 6.06). Ampicillin was the most commonly prescribed antibiotic (42.1%) and parenteral was the most common route prescribed (81.4%). The data on hospital indicators showed key antibiotics were out of stock on average for 78.18 days; 87.5% of key antibiotics were available on the day of the study. The data on patient care indicator showed patients taking antibiotics stayed in the hospital for 9.97 days (± 7.33 days).}, } @article {pmid30563556, year = {2018}, author = {Cziesielski, MJ and Liew, YJ and Aranda, M}, title = {Summarized datasheet for multi-omics response of three Exaiptasia strains to heat stress: a new way to process omics data.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {905}, doi = {10.1186/s13104-018-4018-x}, pmid = {30563556}, issn = {1756-0500}, abstract = {OBJECTIVES: Corals, the building blocks of reef ecosystems, have been severely threatened by climate change. Coral bleaching, the loss of the coral's endosymbiotic algae, occurs as a consequence of increasing ocean temperature. To understand mechanisms of stress tolerance in symbiotic cnidarians, the sea anemone Exaiptasia pallida from different regions was heat stressed. The three strains originated from the Red Sea, Hawaii and North Carolina, each with different temperature profiles, enabling a comparative study of local adaptation strategies.

DATA DESCRIPTION: Whole transcriptome and proteome data were collected from all anemones at control and stress condition. As part of the analysis of this large, multi-omic data, we wrote a script that creates a tabular datasheet that summarized the transcriptomic and proteomic changes for every gene. It facilitates the search of individual genes, or a group of genes, their up- or downregulation during stress and whether this change in expression was statistically significant. Furthermore, it enables examining if changes in RNA correspond to those in proteins. The datasheet can be used for future comparisons, as well as search and development of biomarkers.}, } @article {pmid30563508, year = {2018}, author = {Wu, Z and Senchuk, MM and Dues, DJ and Johnson, BK and Cooper, JF and Lew, L and Machiela, E and Schaar, CE and DeJonge, H and Blackwell, TK and Van Raamsdonk, JM}, title = {Mitochondrial unfolded protein response transcription factor ATFS-1 promotes longevity in a long-lived mitochondrial mutant through activation of stress response pathways.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {147}, doi = {10.1186/s12915-018-0615-3}, pmid = {30563508}, issn = {1741-7007}, support = {R01 GM121756/GM/NIGMS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R01 AG054215/AG/NIA NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; R35 GM122610/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: The mitochondrial unfolded protein response (mitoUPR) is a stress response pathway activated by disruption of proteostasis in the mitochondria. This pathway has been proposed to influence lifespan, with studies suggesting that mitoUPR activation has complex effects on longevity.

RESULTS: Here, we examined the contribution of the mitoUPR to the survival and lifespan of three long-lived mitochondrial mutants in Caenorhabditis elegans by modulating the levels of ATFS-1, the central transcription factor that mediates the mitoUPR. We found that clk-1, isp-1, and nuo-6 worms all exhibit an ATFS-1-dependent activation of the mitoUPR. While loss of atfs-1 during adulthood does not affect lifespan in any of these strains, absence of atfs-1 during development prevents clk-1 and isp-1 worms from reaching adulthood and reduces the lifespan of nuo-6 mutants. Examining the mechanism by which deletion of atfs-1 reverts nuo-6 lifespan to wild-type, we find that many of the transcriptional changes present in nuo-6 worms are mediated by ATFS-1. Genes exhibiting an ATFS-1-dependent upregulation in nuo-6 worms are enriched for transcripts that function in stress response and metabolism. Consistent, with this finding, loss of atfs-1 abolishes the enhanced stress resistance observed in nuo-6 mutants and prevents upregulation of multiple stress response pathways including the HIF-1-mediated hypoxia response, SKN-1-mediated oxidative stress response and DAF-16-mediated stress response.

CONCLUSIONS: Our results suggest that in the long-lived mitochondrial mutant nuo-6 activation of the mitoUPR causes atfs-1-dependent changes in the expression of genes involved in stress response and metabolism, which contributes to the extended longevity observed in this mutant. This work demonstrates that the mitoUPR can modulate multiple stress response pathways and suggests that it is crucial for the development and lifespan of long-lived mitochondrial mutants.}, } @article {pmid30563470, year = {2018}, author = {Crosby, FL and Lundgren, AM and Hoffman, C and Pascual, DW and Barbet, AF}, title = {VirB10 vaccination for protection against Anaplasma phagocytophilum.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {217}, doi = {10.1186/s12866-018-1346-x}, pmid = {30563470}, issn = {1471-2180}, support = {U54 AI057156/AI/NIAID NIH HHS/United States ; U54AI057156//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: Human granulocytic anaplasmosis (HGA) is a tick-borne disease caused by the etiologic agent Anaplasma phagocytophilum. HGA was designated a nationally notifiable disease in the United States in 1998. Currently there are no vaccines available against HGA. Conserved membrane proteins that are subdominant in Anaplasma species, such as VirB9 and VirB10, may represent better vaccine targets than the variable immunodominant surface proteins. VirB9 and VirB10 are constituents of the Type 4 secretion system (T4SS) that is conserved amongst many intracellular bacteria and performs essential functions for invasion and survival in host cells.

RESULTS: Immunogenicity and contribution to protection, provided after intramuscular vaccination of plasmid DNA encoding VirB9-1, VirB9-2, and VirB10 followed by inoculation of homologous recombinant proteins, in a prime-boost immunization strategy was evaluated in a murine model of HGA. Recombinant VirB9-1-, VirB9-2-, and VirB10-vaccinated mice developed antibody responses that specifically reacted with A. phagocytophilum organisms. However, only the mice vaccinated with VirB10 developed a significant increase in IFN-γ CD4+ T cells and partial protection against challenge with A. phagocytophilum.

CONCLUSIONS: This work provides evidence that A. phagocytophilum T4SS VirB10 is partially protective in a murine model against infection in an IFN-γ-dependent fashion and suggests that this protein may be a potential vaccine candidate against this and possibly other pathogenic bacteria with a T4SS.}, } @article {pmid30563469, year = {2018}, author = {Wan, J and Zhang, P and Wang, R and Sun, L and Ju, Q and Xu, J}, title = {Comparative physiological responses and transcriptome analysis reveal the roles of melatonin and serotonin in regulating growth and metabolism in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {362}, doi = {10.1186/s12870-018-1548-2}, pmid = {30563469}, issn = {1471-2229}, support = {(31772383, 31272239)//National Natural Science Foundation of China (CN)/ ; (2016YFC0501901)//National Key Research and Development Program of China/ ; (2017-ZJ-Y20)//Qinghai innovation platform construction project/ ; (2014HB043)//Yunnan Province Foundation for academic leader/ ; }, mesh = {Arabidopsis/drug effects/genetics/*growth & development/*metabolism ; Carbon/metabolism ; Disease Resistance/drug effects/physiology ; Gene Expression Profiling ; Gene Expression Regulation, Plant/drug effects ; Iron/metabolism ; Melatonin/*metabolism/pharmacology ; Nitrogen/metabolism ; Photosynthesis/drug effects ; Plant Leaves/drug effects/physiology ; Plant Roots/drug effects/physiology ; Plants, Genetically Modified ; Seedlings/drug effects/genetics ; Serotonin/*metabolism/pharmacology ; }, abstract = {BACKGROUND: Melatonin and serotonin are well-known signaling molecules that mediate multiple physiological activities in plants, including stress defense, growth, development, and morphogenesis, but their underlying mechanisms have not yet been thoroughly elucidated. In this study, we investigated the roles of melatonin and serotonin in modulating plant growth and defense by integrating physiological and transcriptome analyses in Arabidopsis.

RESULTS: Moderate concentrations of melatonin and serotonin did not affect primary root (PR) growth but markedly induced lateral root (LR) formation. Both melatonin and serotonin locally induced the expression of the cell-wall-remodeling-related genes LBD16 and XTR6, thereby inducing LR development. Our data support the idea that melatonin and serotonin lack any auxin-like activity. Treatment with 50 μM serotonin significantly improved PSII activity, and the transcriptome data supported this result. Melatonin and serotonin slightly affected glycolysis and the TCA cycle; however, they markedly regulated the catabolism of several key amino acids, thereby affecting carbon metabolism and energy metabolism. Melatonin and serotonin improved iron (Fe) deficiency tolerance by inducing Fe-responsive gene expression.

CONCLUSIONS: Overall, our results from the physiological and transcriptome analyses reveal the roles of melatonin and serotonin in modulating plant growth and stress responses and provide insight into novel crop production strategies using these two phytoneurotransmitters.}, } @article {pmid30563467, year = {2018}, author = {McLaughlin, HP and Sue, D}, title = {Rapid antimicrobial susceptibility testing and β-lactam-induced cell morphology changes of Gram-negative biological threat pathogens by optical screening.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {218}, doi = {10.1186/s12866-018-1347-9}, pmid = {30563467}, issn = {1471-2180}, support = {HDTRA1213740//U.S. Department of Defense/ ; HDTRA1213740//Defense Threat Reduction Agency/ ; HDTRA1213740//Joint Science and Technology Office/ ; }, abstract = {BACKGROUND: For Yersinia pestis, Burkholderia pseudomallei, and Burkholderia mallei, conventional broth microdilution (BMD) is considered the gold standard for antimicrobial susceptibility testing (AST) and, depending on the species, requires an incubation period of 16-20 h, or 24-48 h according to the Clinical and Laboratory Standards Institute (CLSI) guidelines. After a diagnosis of plague, melioidosis or glanders during an outbreak or after an exposure event, the timely distribution of appropriate antibiotics for treatment or post-exposure prophylaxis of affected populations could reduce mortality rates.

RESULTS: Herein, we developed and evaluated a rapid, automated susceptibility test for these Gram-negative bacterial pathogens based on time-lapse imaging of cells incubating in BMD microtitre drug panels using an optical screening instrument (oCelloScope). In real-time, the instrument screened each inoculated well containing broth with various concentrations of antibiotics published by CLSI for primary testing: ciprofloxacin (CIP), doxycycline (DOX) and gentamicin (GEN) for Y. pestis; imipenem (IPM), ceftazidime (CAZ) and DOX for B. mallei; and IPM, DOX, CAZ, amoxicillin-clavulanic acid (AMC) and trimethoprim-sulfamethoxazole (SXT) for B. pseudomallei. Based on automated growth kinetic data, the time required to accurately determine susceptibility decreased by ≥70% for Y. pestis and ≥ 50% for B. mallei and B. pseudomallei compared to the times required for conventional BMD testing. Susceptibility to GEN, IPM and DOX could be determined in as early as three to six hours. In the presence of CAZ, susceptibility based on instrument-derived growth values could not be determined for the majority of B. pseudomallei and B. mallei strains tested. Time-lapse video imaging of these cultures revealed that the formation of filaments in the presence of this cephalosporin at inhibitory concentrations was detected as growth. Other β-lactam-induced cell morphology changes, such as the formation of spheroplasts and rapid cell lysis, were also observed and appear to be strain- and antibiotic concentration-dependent.

CONCLUSIONS: A rapid, functional AST was developed and real-time video footage captured β-lactam-induced morphologies of wild-type B. mallei and B. pseudomallei strains in broth. Optical screening reduced the time to results required for AST of three Gram-negative biothreat pathogens using clinically relevant, first-line antibiotics compared to conventional BMD.}, } @article {pmid30563465, year = {2018}, author = {Song, W and Ovcharenko, I}, title = {Dichotomy in redundant enhancers points to presence of initiators of gene regulation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {947}, doi = {10.1186/s12864-018-5335-0}, pmid = {30563465}, issn = {1471-2164}, support = {Intramural Research Program//U.S. National Library of Medicine/ ; }, abstract = {BACKGROUND: The regulatory landscape of a gene locus often consists of several functionally redundant enhancers establishing phenotypic robustness and evolutionary stability of its regulatory program. However, it is unclear what mechanisms are employed by redundant enhancers to cooperatively orchestrate gene expression.

RESULTS: By comparing redundant enhancers to single enhancers (enhancers present in a single copy in a gene locus), we observed that the DNA sequence encryption differs between these two classes of enhancers, suggesting a difference in their regulatory mechanisms. Initiator enhancers, which are a subset of redundant enhancers and show similar sequence encryption to single enhancers, differ from the rest of redundant enhancers in their sequence encryption, evolutionary conservation and proximity to target genes. Genes hosting initiator enhancers in their loci feature elevated levels of expression. Initiator enhancers show a high level of 3D chromatin contacts with both transcription start sites and regular enhancers, suggesting their roles as primary activators and intermediate catalysts of gene expression, through which the regulatory signals of redundant enhancers are propagated to the target genes. In addition, GWAS and eQTLs variants are significantly enriched in initiator enhancers compared to redundant enhancers, suggesting a key functional role these sequences play in gene regulation.

CONCLUSIONS: The specific characteristics and widespread abundance of initiator enhancers advocate for a possible universal hierarchical mechanism of tissue-specific gene regulation involving multiple redundant enhancers acting through initiator enhancers.}, } @article {pmid30563464, year = {2018}, author = {Zhu, H and Li, S and Hu, Z and Liu, G}, title = {Molecular characterization of eukaryotic algal communities in the tropical phyllosphere based on real-time sequencing of the 18S rDNA gene.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {365}, doi = {10.1186/s12870-018-1588-7}, pmid = {30563464}, issn = {1471-2229}, support = {31600168//National Natural Science Foundation of China/ ; 31870189//National Natural Science Foundation of China/ ; ZDRWZS-2017-221//Chinese Academy of Sciences Key deployment project/ ; }, mesh = {China ; Chlorophyceae/classification/genetics ; Chlorophyta/classification/*genetics ; *DNA, Ribosomal ; Ecosystem ; Phylogeny ; Polymerase Chain Reaction ; *Trees ; Tropical Climate ; }, abstract = {BACKGROUD: Foliicolous algae are a common occurrence in tropical forests. They are referable to a few simple morphotypes (unicellular, sarcinoid-like or filamentous), which makes their morphology of limited usefulness for taxonomic studies and species diversity assessments. The relationship between algal community and their host phyllosphere was not clear. In order to obtain a more accurate assessment, we used single molecule real-time sequencing of the 18S rDNA gene to characterize the eukaryotic algal community in an area of South-western China.

RESULT: We annotated 2922 OTUs belonging to five classes, Ulvophyceae, Trebouxiophyceae, Chlorophyceae, Dinophyceae and Eustigmatophyceae. Novel clades formed by large numbers sequences of green algae were detected in the order Trentepohliales (Ulvophyceae) and the Watanabea clade (Trebouxiophyceae), suggesting that these foliicolous communities may be substantially more diverse than so far appreciated and require further research. Species in Trentepohliales, Watanabea clade and Apatococcus clade were detected as the core members in the phyllosphere community studied. Communities from different host trees and sampling sites were not significantly different in terms of OTUs composition. However, the communities of Musa and Ravenala differed from other host plants significantly at the genus level, since they were dominated by Trebouxiophycean epiphytes.

CONCLUSION: The cryptic diversity of eukaryotic algae especially Chlorophytes in tropical phyllosphere is very high. The community structure at species-level has no significant relationship either with host phyllosphere or locations. The core algal community in tropical phyllopshere is consisted of members from Trentepohliales, Watanabea clade and Apatococcus clade. Our study provided a large amount of novel 18S rDNA sequences that will be useful to unravel the cryptic diversity of phyllosphere eukaryotic algae and for comparisons with similar future studies on this type of communities.}, } @article {pmid30563463, year = {2018}, author = {Nandamuri, SP and Conte, MA and Carleton, KL}, title = {Multiple trans QTL and one cis-regulatory deletion are associated with the differential expression of cone opsins in African cichlids.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {945}, doi = {10.1186/s12864-018-5328-z}, pmid = {30563463}, issn = {1471-2164}, support = {R01 EY024639/EY/NEI NIH HHS/United States ; R01EY024639//National Eye Institute/ ; }, abstract = {BACKGROUND: Dissecting the genetic basis of phenotypic diversity is one of the fundamental goals in evolutionary biology. Despite growing evidence for gene expression divergence being responsible for the evolution of complex traits, knowledge about the proximate genetic causes underlying these traits is still limited. African cichlids have diverse visual systems, with different species expressing different combinations of seven cone opsin genes. Using opsin expression variation in African cichlids as a model for gene expression evolution, this study aims to investigate the genetic architecture of opsin expression divergence in this group.

RESULTS: Results from a genome-wide linkage mapping on the F2 progeny of an intergeneric cross, between two species with differential opsin expression show that opsins in Lake Malawi cichlids are controlled by multiple quantitative trait loci (QTLs). Most of these QTLs are located in trans to the opsins except for one cis-QTL for SWS1 on LG17. A closer look at this major QTL revealed the presence of a 691 bp deletion in the promoter of the SWS1 opsin (located 751 bp upstream of the start site) that is associated with a decrease in its expression. Phylogenetic footprinting indicates that the region spanning the deletion harbors a microRNA miR-729 and a conserved non-coding element (CNE) that also occurs in zebrafish and other teleosts. This suggests that the deletion might contain ancestrally preserved regulators that have been tuned for SWS1 gene expression in Lake Malawi. While this deletion is not common, it does occur in several other species within the lake.

CONCLUSIONS: Differential expression of cichlid opsins is associated with multiple overlapping QTL, with all but one in trans to the opsins they regulate. The one cis-acting factor is a deletion in the promoter of the SWS1 opsin, suggesting that ancestral polymorphic deletions may contribute to cichlid's visual diversity. In addition to expanding our understanding of the molecular landscape of opsin expression in African cichlids, this study sheds light on the molecular mechanisms underlying phenotypic variation in natural populations.}, } @article {pmid30563462, year = {2018}, author = {Li, WF and Mao, J and Yang, SJ and Guo, ZG and Ma, ZH and Dawuda, MM and Zuo, CW and Chu, MY and Chen, BH}, title = {Anthocyanin accumulation correlates with hormones in the fruit skin of 'Red Delicious' and its four generation bud sport mutants.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {363}, doi = {10.1186/s12870-018-1595-8}, pmid = {30563462}, issn = {1471-2229}, support = {GSAU-XKJS-2018-230//Discipline Construction Fund Project of Gansu Agricultural University/ ; 2017002//Fostering Foundation for the Excellent Ph.D. Dissertation of Gansu Agricultural University/ ; 18ZD2NA006//Science and Technology Major Project of Gansu Province/ ; }, mesh = {Anthocyanins/genetics/*metabolism ; Flavonoids/genetics/metabolism ; Fruit/genetics/growth & development/*metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant ; Malus/*genetics/*metabolism ; Mutation ; Pigmentation/genetics ; Plant Growth Regulators/genetics/*metabolism ; Plant Proteins/genetics/metabolism ; Terpenes/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Bud sport mutants of apple (Malus domestica Borkh.) trees with a highly blushed colouring pattern are mainly caused by the accumulation of anthocyanins in the fruit skin. Hormones are important factors modulating anthocyanin accumulation. However, a good understanding of the interplay between hormones and anthocyanin synthesis in apples, especially in mutants at the molecular level, remains elusive. Here, physiological and comparative transcriptome approaches were used to reveal the molecular basis of color pigmentation in the skin of 'Red Delicious' (G0) and its mutants, including 'Starking Red' (G1), 'Starkrimson' (G2), 'Campbell Redchief' (G3) and 'Vallee spur' (G4).

RESULTS: Pigmentation in the skin gradually proliferated from G0 to G4. The anthocyanin content was higher in the mutants than in 'Red Delicious'. The activation of early phenylpropanoid biosynthesis genes, including ASP3, PAL, 4CL, PER, CHS, CYP98A and F3'H, was more responsible for anthocyanin accumulation in mutants at the color break stage. In addition, IAA and ABA had a positive regulatory effect on the synthesis of anthocyanins, while GA had the reverse effect. The down-regulation of AACT1, HMGS, HMGR, MVK, MVD2, IDI1 and FPPS2 involved in terpenoid biosynthesis influences anthocyanin accumulation by positively regulating transcripts of AUX1 and SAUR that contribute to the synthesis of IAA, GID2 to GA, PP2C and SnRK2 to ABA. Furthermore, MYB and bHLH members, which are highly correlated (r=0.882-0.980) with anthocyanin content, modulated anthocyanin accumulation by regulating the transcription of structural genes, including CHS and F3'H, involved in the flavonoid biosynthesis pathway.

CONCLUSIONS: The present comprehensive transcriptome analyses contribute to the understanding of the the relationship between hormones and anthocyanin synthesis as well as the molecular mechanism involved in apple skin pigmentation.}, } @article {pmid30563461, year = {2018}, author = {Smith, HM and Clarke, CW and Smith, BP and Carmody, BM and Thomas, MR and Clingeleffer, PR and Powell, KS}, title = {Genetic identification of SNP markers linked to a new grape phylloxera resistant locus in Vitis cinerea for marker-assisted selection.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {360}, doi = {10.1186/s12870-018-1590-0}, pmid = {30563461}, issn = {1471-2229}, support = {CSP1304//Wine Australia/ ; }, mesh = {Alleles ; Animals ; Chromosome Mapping ; *Hemiptera ; Plant Breeding/*methods ; *Polymorphism, Single Nucleotide ; Reproducibility of Results ; Vitis/*genetics ; }, abstract = {BACKGROUND: Grape phylloxera (Daktulosphaira vitifoliae Fitch) is a major insect pest that negatively impacts commercial grapevine performance worldwide. Consequently, the use of phylloxera resistant rootstocks is an essential component of vineyard management. However, the majority of commercially available rootstocks used in viticulture production provide limited levels of grape phylloxera resistance, in part due to the adaptation of phylloxera biotypes to different Vitis species. Therefore, there is pressing need to develop new rootstocks better adapted to specific grape growing regions with complete resistance to grape phylloxera biotypes.

RESULTS: Grapevine rootstock breeding material, including an accession of Vitis cinerea and V. aestivalis, DRX55 ([M. rotundifolia x V. vinifera] x open pollinated) and MS27-31 (M. rotundifolia specific hybrid), provided complete resistance to grape phylloxera in potted plant assays. To map the genetic factor(s) of grape phylloxera resistance, a F1 V. cinerea x V. vinifera Riesling population was screened for resistance. Heritability analysis indicates that the V. cinerea accession contained a single allele referred as RESISTANCE TO DAKTULOSPHAIRA VITIFOLIAE 2 (RDV2) that confers grape phylloxera resistance. Using genetic maps constructed with pseudo-testcross markers for V. cinerea and Riesling, a single phylloxera resistance locus was identified in V. cinerea. After validating SNPs at the RDV2 locus, interval and linkage mapping showed that grape phylloxera resistance mapped to linkage group 14 at position 16.7 cM.

CONCLUSION: The mapping of RDV2 and the validation of markers linked to grape phylloxera resistance provides the basis to breed new rootstocks via marker-assisted selection that improve vineyard performance.}, } @article {pmid30563460, year = {2018}, author = {Ming, T and Han, J and Li, Y and Lu, C and Qiu, D and Li, Y and Zhou, J and Su, X}, title = {A metabolomics and proteomics study of the Lactobacillus plantarum in the grass carp fermentation.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {216}, doi = {10.1186/s12866-018-1354-x}, pmid = {30563460}, issn = {1471-2180}, support = {2017YFC 1404505//National Key R&D Program of China/ ; 2015B05//Zhejiang pharmaceutical college research fund project/ ; Y201635803//General project of Zhejiang Provincial Education Department/ ; XYL17015//Fund in Ningbo University/ ; }, abstract = {BACKGROUND: Lactobacillus plantarum, a versatile lactic acid-fermenting bacterium, isolated from the traditional pickles in Ningbo of China, was chosen for grass carp fermentation, which could also improve the flavor of grass carp. We here explored the central metabolic pathways of L. plantarum by using metabolomic approach, and further proved the potential for metabolomics combined with proteomics approaches for the basic research on the changes of metabolites and the corresponding fermentation mechanism of L. plantarum fermentation.

RESULTS: This study provides a cellular material footprinting of more than 77 metabolites and 27 proteins in L. plantarum during the grass carp fermentation. Compared to control group, cells displayed higher levels of proteins associated with glycolysis and nucleotide synthesis, whereas increased levels of serine, ornithine, aspartic acid, 2-piperidinecarboxylic acid, and fumarate, along with decreased levels of alanine, glycine, threonine, tryptophan, and lysine.

CONCLUSIONS: Our results may provide a deeper understanding of L. plantarum fermentation mechanism based on metabolomics and proteomic analysis and facilitate future investigations into the characterization of L. plantarum during the grass carp fermentation.}, } @article {pmid30563458, year = {2018}, author = {Medina, C and da Rocha, M and Magliano, M and Raptopoulo, A and Marteu, N and Lebrigand, K and Abad, P and Favery, B and Jaubert-Possamai, S}, title = {Characterization of siRNAs clusters in Arabidopsis thaliana galls induced by the root-knot nematode Meloidogyne incognita.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {943}, doi = {10.1186/s12864-018-5296-3}, pmid = {30563458}, issn = {1471-2164}, support = {ANR-11-LABX-0028-01//Agence Nationale de la Recherche/ ; ANR-13-KBBE-0003-06//Agence Nationale de la Recherche/ ; ANR-10-INBS-09//Agence Nationale de la Recherche/ ; }, abstract = {BACKGROUND: Root-knot nematodes (RKN), genus Meloidogyne, are plant parasitic worms that have the ability to transform root vascular cylinder cells into hypertrophied, multinucleate and metabolically over-active feeding cells. Redifferentiation into feeding cells is the result of a massive transcriptional reprogramming of root cells targeted by RKN. Since RKN are able to induce similar feeding cells in roots of thousands of plant species, these worms are thought to manipulate essential and conserved plant molecular pathways.

RESULTS: Small non-coding RNAs of uninfected roots and infected root galls induced by M. incognita from Arabidopsis thaliana were sequenced by high throughput sequencing. SiRNA populations were analysed by using the Shortstack algorithm. We identified siRNA clusters that are differentially expressed in infected roots and evidenced an over-representation of the 23-24 nt siRNAs in infected tissue. This size corresponds to heterochromatic siRNAs (hc-siRNAs) which are known to regulate expression of transposons and genes at the transcriptional level, mainly by inducing DNA methylation.

CONCLUSIONS: Correlation of siRNA clusters expression profile with transcriptomic data identified several protein coding genes that are candidates to be regulated by siRNAs at the transcriptional level by RNA directed DNA methylation (RdDM) pathway either directly or indirectly via silencing of neighbouring transposable elements.}, } @article {pmid30563457, year = {2018}, author = {Chen, X and Zhang, M and Wang, M and Tan, G and Zhang, M and Hou, YX and Wang, B and Li, Z}, title = {The effects of mepiquat chloride on the lateral root initiation of cotton seedlings are associated with auxin and auxin-conjugate homeostasis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {361}, doi = {10.1186/s12870-018-1599-4}, pmid = {30563457}, issn = {1471-2229}, support = {Grant No. 31471434//National Natural Science Foundation of China/ ; }, mesh = {Amidohydrolases/genetics ; Animals ; Antibodies, Monoclonal ; Arabidopsis/drug effects/genetics ; Arabidopsis Proteins/genetics ; Cloning, Molecular ; Enzyme-Linked Immunosorbent Assay/methods ; Gene Expression Regulation, Plant ; Gossypium/*drug effects/genetics/growth & development/metabolism ; Homeostasis/drug effects ; Indoleacetic Acids/*metabolism ; Mice ; Mutation ; Piperidines/*pharmacology ; Plant Growth Regulators/*pharmacology ; Plant Proteins/genetics/immunology/metabolism ; Plant Roots/*drug effects/growth & development/metabolism ; Seedlings/drug effects/growth & development ; }, abstract = {BACKGROUND: Mepiquat chloride (MC) is a plant growth regulator widely used in cotton (Gossypium hirsutum L.) production to suppress excessive vegetative growth, increase root growth and avoid yield losses. To increase root growth, cotton seeds were treated with MC to increase the number of lateral root (LRs) and improve drought resistance. An increased indole-3-acetic acid (IAA) pool appeared to correlate with LR growth, and the principal source of IAA in germinating seeds is IAA conjugates. Here, the role of IAA homeostasis and signaling was investigated in cotton seedlings treated with MC.

RESULTS: In the present research, MC significantly increased endogenous IAA levels in the roots, which promoted lateral root initiation (LRI) by upregulating GhARF7/19 and GhLBD18s and subsequently increasing LR quantity and elongation. The levels of IAA-amide conjugates significantly decreased in MC-treated seedlings compared with untreated control seedlings. Sixteen members of the cotton IAA amidohydrolase (IAH) gene family were identified, of which GhIAR3a, GhIAR3b, GhILR1, GhILL3 and GhILL6 were expressed during cotton seed germination. Compared with those in untreated control seedlings, the expression levels of GhIAR3a, GhIAR3b, GhILR1 and GhILL6 in the MC-treated seedlings were markedly elevated. The GhIAR3a/b and GhILR1 genes were cloned and expressed in Escherichia coli; these recombinant proteins exhibited hydrolytic activity that could cleave IAA-phenyalanine (Phe), IAA-methionine (Met), IAA-glycine (Gly) and IAA-leucine (Leu) in vitro, while only GhIAR3a hydrolyzed IAA-alanine (Ala) efficiently. The content of GhIAR3a, as detected via an established sandwich enzyme-linked immunosorbent assay (ELISA), increased in the MC-treated seedlings compared with the untreated control seedlings. In addition, the Arabidopsis iar3 mutant was less responsive to MC-induced LR growth than was wild type.

CONCLUSIONS: These findings suggested that MC application could mediate IAA homeostasis via increased IAA levels from IAA-amide conjugate hydrolysis by accelerating IAH gene expression, which might promote LRI and increase the LR quantity and elongation.}, } @article {pmid30563456, year = {2018}, author = {Siadjeu, C and Mayland-Quellhorst, E and Albach, DC}, title = {Genetic diversity and population structure of trifoliate yam (Dioscorea dumetorum Kunth) in Cameroon revealed by genotyping-by-sequencing (GBS).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {359}, doi = {10.1186/s12870-018-1593-x}, pmid = {30563456}, issn = {1471-2229}, support = {57299294//German Academic Exchange Service (DAAD)/ ; }, mesh = {Cameroon ; Dioscorea/*genetics ; *Genetic Variation ; Genetics, Population ; Genome Size ; Genome, Plant ; Genotyping Techniques/*methods ; Phylogeny ; Ploidies ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Yams (Dioscorea spp.) are economically important food for millions of people in the humid and sub-humid tropics. Dioscorea dumetorum (Kunth) is the most nutritious among the eight-yam species, commonly grown and consumed in West and Central Africa. Despite these qualities, the storage ability of D. dumetorum is restricted by severe postharvest hardening of the tubers that can be addressed through concerted breeding efforts. The first step of any breeding program is bound to the study of genetic diversity. In this study, we used the Genotyping-By-Sequencing of Single Nucleotide Polymorphism (GBS-SNP) to investigate the genetic diversity and population structure of 44 accessions of D. dumetorum in Cameroon. Ploidy was inferred using flow cytometry and gbs2ploidy.

RESULTS: We obtained on average 6371 loci having at least information for 75% accessions. Based on 6457 unlinked SNPs, our results demonstrate that D. dumetorum is structured into four populations. We clearly identified, a western/north-western, a western, and south-western populations, suggesting that altitude and farmers-consumers preference are the decisive factors for differential adaptation and separation of these populations. Bayesian and neighbor-joining clustering detected the highest genetic variability in D. dumetorum accessions from the south-western region. This variation is likely due to larger breeding efforts in the region as shown by gene flow between D. dumetorum accessions from the south-western region inferred by maximum likelihood. Ploidy analysis revealed diploid and triploid levels in D. dumetorum accessions with mostly diploid accessions (77%). Male and female accessions were mostly triploid (75%) and diploid (69%), respectively. The 1C genome size values of D. dumetorum accessions were on average 0.333 ± 0.009 pg and 0.519 ± 0.004 pg for diploids and triploids, respectively.

CONCLUSIONS: Germplasm characterization, population structure and ploidy are an essential basic information in a breeding program as well as for conservation of intraspecific diversity. Thus, results obtained in this study provide valuable information for the improvement and conservation of D. dumetorum. Moreover, GBS appears as an efficient powerful tool to detect intraspecific variation.}, } @article {pmid30563453, year = {2018}, author = {Harman, A and Barth, C}, title = {The Dictyostelium discoideum homologue of Twinkle, Twm1, is a mitochondrial DNA helicase, an active primase and promotes mitochondrial DNA replication.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {12}, doi = {10.1186/s12867-018-0114-7}, pmid = {30563453}, issn = {1471-2199}, abstract = {BACKGROUND: DNA replication requires contributions from various proteins, such as DNA helicases; in mitochondria Twinkle is important for maintaining and replicating mitochondrial DNA. Twinkle helicases are predicted to also possess primase activity, as has been shown in plants; however this activity appears to have been lost in metazoans. Given this, the study of Twinkle in other organisms is required to better understand the evolution of this family and the roles it performs within mitochondria.

RESULTS: Here we describe the characterization of a Twinkle homologue, Twm1, in the amoeba Dictyostelium discoideum, a model organism for mitochondrial genetics and disease. We show that Twm1 is important for mitochondrial function as it maintains mitochondrial DNA copy number in vivo. Twm1 is a helicase which unwinds DNA resembling open forks, although it can act upon substrates with a single 3' overhang, albeit less efficiently. Furthermore, unlike human Twinkle, Twm1 has primase activity in vitro. Finally, using a novel in bacterio approach, we demonstrated that Twm1 promotes DNA replication.

CONCLUSIONS: We conclude that Twm1 is a replicative mitochondrial DNA helicase which is capable of priming DNA for replication. Our results also suggest that non-metazoan Twinkle could function in the initiation of mitochondrial DNA replication. While further work is required, this study has illuminated several alternative processes of mitochondrial DNA maintenance which might also be performed by the Twinkle family of helicases.}, } @article {pmid30563451, year = {2018}, author = {Bae, J and Lee, KW and Islam, MN and Yim, HS and Park, H and Rho, M}, title = {iMGEins: detecting novel mobile genetic elements inserted in individual genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {944}, doi = {10.1186/s12864-018-5290-9}, pmid = {30563451}, issn = {1471-2164}, support = {No. 20180430//Ministry of Oceans and Fisheries/ ; 2017M3A9F3041232//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Recent advances in sequencing technology have allowed us to investigate personal genomes to find structural variations, which have been studied extensively to identify their association with the physiology of diseases such as cancer. In particular, mobile genetic elements (MGEs) are one of the major constituents of the human genomes, and cause genome instability by insertion, mutation, and rearrangement.

RESULT: We have developed a new program, iMGEins, to identify such novel MGEs by using sequencing reads of individual genomes, and to explore the breakpoints with the supporting reads and MGEs detected. iMGEins is the first MGE detection program that integrates three algorithmic components: discordant read-pair mapping, split-read mapping, and insertion sequence assembly. Our evaluation results showed its outstanding performance in detecting novel MGEs from simulated genomes, as well as real personal genomes. In detail, the average recall and precision rates of iMGEins are 96.67 and 100%, respectively, which are the highest among the programs compared. In the testing with real human genomes of the NA12878 sample, iMGEins shows the highest accuracy in detecting MGEs within 20 bp proximity of the breakpoints annotated.

CONCLUSION: In order to study the dynamics of MGEs in individual genomes, iMGEins was developed to accurately detect breakpoints and report inserted MGEs. Compared with other programs, iMGEins has valuable features of identifying novel MGEs and assembling the MGEs inserted.}, } @article {pmid30563450, year = {2018}, author = {Serra, S and Sullivan, N and Mattheis, JP and Musacchi, S and Rudell, DR}, title = {Canopy attachment position influences metabolism and peel constituency of European pear fruit.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {364}, doi = {10.1186/s12870-018-1544-6}, pmid = {30563450}, issn = {1471-2229}, support = {PR14-108A//Washington Tree Fruit Research Commission/ ; 2094-43000-007-00-D//Agricultural Research Service/ ; }, mesh = {*Food Storage ; Fruit/*metabolism ; *Metabolic Networks and Pathways ; Phytosterols/metabolism ; Principal Component Analysis ; Pyrus/metabolism/*physiology ; Sesquiterpenes/metabolism ; }, abstract = {BACKGROUND: Inconsistent pear fruit ripening resulting from variable harvest maturity within tree canopies can contribute to postharvest losses through senescence and spoilage that would otherwise be effectively managed using crop protectant and storage regimes. Because those inconsistencies are likely based on metabolic differences, non-targeted metabolic profiling peel of 'd'Anjou' pears harvested from the external or internal canopy was used to determine the breadth of difference and link metabolites with canopy position during long-term controlled atmosphere storage.

RESULTS: Differences were widespread, encompassing everything from expected distinctions in flavonol glycoside levels between peel of fruit from external and internal canopy positions to increased aroma volatile production and sucrose hydrolysis with ripening. Some of the most substantial differences were in levels of triterpene and phenolic peel cuticle components among which acyl esters of ursolic acid and fatty acyl esters of p-coumaryl alcohol were higher in the cuticle of fruit from external tree positions, and acyl esters of α-amyrin were elevated in peel of fruit from internal positions. Possibly the most substantial dissimilarities were those that were directly related to fruit quality. Phytosterol conjugates and sesquiterpenes related to elevated superficial scald risk were higher in pears from external positions which were to be potentially rendered unmarketable by superficial scald. Other metabolites associated with fruit aroma and flavor became more prevalent in external fruit peel as ripening progressed and, likewise, with differential soluble solids and ethylene levels, suggesting the final product not only ripens differentially but the final fruit quality following ripening is actually different based on the tree position.

CONCLUSIONS: Given the impact tree position appears to have on the most intrinsic aspects of ripening and quality, every supply chain management strategy would likely lead to diverse storage outcomes among fruit from most orchards, especially those with large canopies. Metabolites consistently associated with peel of fruit from a particular canopy position may provide targets for non-destructive pre-storage sorting used to reduce losses contributed by this inconsistency.}, } @article {pmid30563449, year = {2018}, author = {Nguyen, JT and Fong, J and Fong, D and Fong, T and Lucero, RM and Gallimore, JM and Burata, OE and Parungao, K and Rascón, AA}, title = {Soluble expression of recombinant midgut zymogen (native propeptide) proteases from the Aedes aegypti Mosquito Utilizing E. coli as a host.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {12}, doi = {10.1186/s12858-018-0101-0}, pmid = {30563449}, issn = {1471-2091}, support = {SC3 GM116681/GM/NIGMS NIH HHS/United States ; SC3GM116681//National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: Studying proteins and enzymes involved in important biological processes in the Aedes aegypti mosquito is limited by the quantity that can be directly isolated from the mosquito. Adding to this difficulty, digestive enzymes (midgut proteases) involved in metabolizing blood meal proteins require a more oxidizing environment to allow proper folding of disulfide bonds. Therefore, recombinant techniques to express foreign proteins in Escherichia coli prove to be effective in producing milligram quantities of the expressed product. However, with the most commonly used strains having a reducing cytoplasm, soluble expression of recombinant proteases is hampered. Fortunately, new E. coli strains with a more oxidizing cytoplasm are now available to ensure proper folding of disulfide bonds.

RESULTS: Utilizing an E. coli strain with a more oxidizing cytoplasm (SHuffle® T7, New England Biolabs) and changes in bacterial growth temperature has resulted in the soluble expression of the four most abundantly expressed Ae. aegypti midgut proteases (AaET, AaSPVI, AaSPVII, and AaLT). A previous attempt of solubly expressing the full-length zymogen forms of these proteases with the leader (signal) sequence and a modified pseudo propeptide with a heterologous enterokinase cleavage site led to insoluble recombinant protein expression. In combination with the more oxidizing cytoplasm, and changes in growth temperature, helped improve the solubility of the zymogen (no leader) native propeptide proteases in E. coli. Furthermore, the approach led to autocatalytic activation of the proteases during bacterial expression and observable BApNA activity. Different time-points after bacterial growth induction were tested to determine the time at which the inactive (zymogen) species is observed to transition to the active form. This helped with the purification and isolation of only the inactive zymogen forms using Nickel affinity.

CONCLUSIONS: The difficulty in solubly expressing recombinant proteases in E. coli is caused by the native reducing cytoplasm. However, with bacterial strains with a more oxidizing cytoplasm, recombinant soluble expression can be achieved, but only in concert with changes in bacterial growth temperature. The method described herein should provide a facile starting point to recombinantly expressing Ae. aegypti mosquito proteases or proteins dependent on disulfide bonds utilizing E. coli as a host.}, } @article {pmid30563448, year = {2018}, author = {Chen, ZQ and Baison, J and Pan, J and Karlsson, B and Andersson, B and Westin, J and García-Gil, MR and Wu, HX}, title = {Accuracy of genomic selection for growth and wood quality traits in two control-pollinated progeny trials using exome capture as the genotyping platform in Norway spruce.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {946}, doi = {10.1186/s12864-018-5256-y}, pmid = {30563448}, issn = {1471-2164}, support = {230-2014-427//Svenska Forskningsrådet Formas/ ; RBP14-0040//Stiftelsen för Strategisk Forskning/ ; }, abstract = {BACKGROUND: Genomic selection (GS) can increase genetic gain by reducing the length of breeding cycle in forest trees. Here we genotyped 1370 control-pollinated progeny trees from 128 full-sib families in Norway spruce (Picea abies (L.) Karst.), using exome capture as genotyping platform. We used 116,765 high-quality SNPs to develop genomic prediction models for tree height and wood quality traits. We assessed the impact of different genomic prediction methods, genotype-by-environment interaction (G × E), genetic composition, size of the training and validation set, relatedness, and number of SNPs on accuracy and predictive ability (PA) of GS.

RESULTS: Using G matrix slightly altered heritability estimates relative to pedigree-based method. GS accuracies were about 11-14% lower than those based on pedigree-based selection. The efficiency of GS per year varied from 1.71 to 1.78, compared to that of the pedigree-based model if breeding cycle length was halved using GS. Height GS accuracy decreased to more than 30% while using one site as training for GS prediction and using this model to predict the second site, indicating that G × E for tree height should be accommodated in model fitting. Using a half-sib family structure instead of full-sib structure led to a significant reduction in GS accuracy and PA. The full-sib family structure needed only 750 markers to reach similar accuracy and PA, as compared to 100,000 markers required for the half-sib family, indicating that maintaining the high relatedness in the model improves accuracy and PA. Using 4000-8000 markers in full-sib family structure was sufficient to obtain GS model accuracy and PA for tree height and wood quality traits, almost equivalent to that obtained with all markers.

CONCLUSIONS: The study indicates that GS would be efficient in reducing generation time of breeding cycle in conifer tree breeding program that requires long-term progeny testing. The sufficient number of trees within-family (16 for growth and 12 for wood quality traits) and number of SNPs (8000) are required for GS with full-sib family relationship. GS methods had little impact on GS efficiency for growth and wood quality traits. GS model should incorporate G × E effect when a strong G × E is detected.}, } @article {pmid30563447, year = {2018}, author = {Cordes, MHJ and Binford, GJ}, title = {Evolutionary dynamics of origin and loss in the deep history of phospholipase D toxin genes.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {194}, doi = {10.1186/s12862-018-1302-2}, pmid = {30563447}, issn = {1471-2148}, support = {R15 GM097676/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Venom-expressed sphingomyelinase D/phospholipase D (SMase D/PLD) enzymes evolved from the ubiquitous glycerophosphoryl diester phosphodiesterases (GDPD). Expression of GDPD-like SMaseD/PLD toxins in both arachnids and bacteria has inspired consideration of the relative contributions of lateral gene transfer and convergent recruitment in the evolutionary history of this lineage. Previous work recognized two distinct lineages, a SicTox-like (ST-like) clade including the arachnid toxins, and an Actinobacterial-toxin like (AT-like) clade including the bacterial toxins and numerous fungal homologs.

RESULTS: Here we expand taxon sampling by homology detection to discover new GDPD-like SMase D/PLD homologs. The ST-like clade now includes homologs in a wider variety of arthropods along with a sister group in Cnidaria; the AT-like clade now includes additional fungal phyla and proteobacterial homologs; and we report a third clade expressed in diverse aquatic metazoan taxa, a few single-celled eukaryotes, and a few aquatic proteobacteria. GDPD-like SMaseD/PLDs have an ancient presence in chelicerates within the ST-like family and ctenophores within the Aquatic family. A rooted phylogenetic tree shows that the three clades derived from a basal paraphyletic group of proteobacterial GDPD-like SMase D/PLDs, some of which are on mobile genetic elements. GDPD-like SMase D/PLDs share a signature C-terminal motif and a shortened βα1 loop, features that distinguish them from GDPDs. The three major clades also have active site loop signatures that distinguish them from GDPDs and from each other. Analysis of molecular phylogenies with respect to organismal relationships reveals a dynamic evolutionary history including both lateral gene transfer and gene duplication/loss.

CONCLUSIONS: The GDPD-like SMaseD/PLD enzymes derive from a single ancient ancestor, likely proteobacterial, and radiated into diverse organismal lineages at least in part through lateral gene transfer.}, } @article {pmid30563445, year = {2018}, author = {Singer, JB and Thomson, EC and McLauchlan, J and Hughes, J and Gifford, RJ}, title = {GLUE: a flexible software system for virus sequence data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {532}, doi = {10.1186/s12859-018-2459-9}, pmid = {30563445}, issn = {1471-2105}, support = {//Wellcome Trust/United Kingdom ; MC UU 12014/12//Medical Research Council/United Kingdom ; MC PC 16045//Medical Research Council/United Kingdom ; 102789/Z/13/Z//Wellcome Trust/United Kingdom ; }, mesh = {Algorithms ; Amino Acid Sequence ; Base Sequence ; Drug Resistance, Viral/genetics ; Genome, Viral ; Genotype ; Genotyping Techniques ; Hepacivirus/*genetics ; Humans ; Likelihood Functions ; Sequence Alignment ; *Software ; Viral Proteins/chemistry ; }, abstract = {BACKGROUND: Virus genome sequences, generated in ever-higher volumes, can provide new scientific insights and inform our responses to epidemics and outbreaks. To facilitate interpretation, such data must be organised and processed within scalable computing resources that encapsulate virology expertise. GLUE (Genes Linked by Underlying Evolution) is a data-centric bioinformatics environment for building such resources. The GLUE core data schema organises sequence data along evolutionary lines, capturing not only nucleotide data but associated items such as alignments, genotype definitions, genome annotations and motifs. Its flexible design emphasises applicability to different viruses and to diverse needs within research, clinical or public health contexts.

RESULTS: HCV-GLUE is a case study GLUE resource for hepatitis C virus (HCV). It includes an interactive public web application providing sequence analysis in the form of a maximum-likelihood-based genotyping method, antiviral resistance detection and graphical sequence visualisation. HCV sequence data from GenBank is categorised and stored in a large-scale sequence alignment which is accessible via web-based queries. Whereas this web resource provides a range of basic functionality, the underlying GLUE project can also be downloaded and extended by bioinformaticians addressing more advanced questions.

CONCLUSION: GLUE can be used to rapidly develop virus sequence data resources with public health, research and clinical applications. This streamlined approach, with its focus on reuse, will help realise the full value of virus sequence data.}, } @article {pmid30562611, year = {2018}, author = {Zurano, JP and Magalhães, FM and Asato, AE and Silva, G and Bidau, CJ and Mesquita, DO and Costa, GC}, title = {Cetartiodactyla: Updating a time-calibrated molecular phylogeny.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {256-262}, doi = {10.1016/j.ympev.2018.12.015}, pmid = {30562611}, issn = {1095-9513}, abstract = {Cetartiodactyla comprises one of the most diverse mammal radiations. Currently, 23 families, 131 genera and more than 330 species are recognized. Several studies have been trying to resolve its phylogenetic relationships. The most comprehensive dated phylogenetic hypothesis available includes only 55% of the extant species, precluding a clear understanding of ecological and evolutionary patterns in Cetartiodactyla. Here, we gathered all mitochondrial genetic data available in GenBank to build a robust Cetartiodactyla calibrated phylogenetic tree using 21 fossil calibration points. We found mitogenomic data for 225 species and included other 93 species from which there was at least one mitochondrial gene available. Using a Bayesian approach, we generated a dated tree comprising 90% of the extant Cetartiodactyla species (n = 318). The major lineages showed robust support and families divergence times are congruent with the available fossil evidence and with previously published phylogenetic hypotheses. By making available a dated phylogeny with extensively sampled clades, we expect to foster future studies on the origin, tempo and mode of Cetartiodactyla diversification.}, } @article {pmid30562610, year = {2019}, author = {Barley, AJ and Nieto-Montes de Oca, A and Reeder, TW and Manríquez-Morán, NL and Arenas Monroy, JC and Hernández-Gallegos, O and Thomson, RC}, title = {Complex patterns of hybridization and introgression across evolutionary timescales in Mexican whiptail lizards (Aspidoscelis).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {284-295}, doi = {10.1016/j.ympev.2018.12.016}, pmid = {30562610}, issn = {1095-9513}, abstract = {Identifying patterns of introgression across the tree of life is foundational to understanding general mechanisms that govern the impacts of gene flow on the speciation process. There are few vertebrate groups in which hybridization is associated with as large a diversity of outcomes as in North American whiptail lizards (Aspidoscelis). Of particular interest is that hybridization among divergent whiptail species has repeatedly led to the formation of unisexual (parthenogenetic) lineages. Understanding the hybrid origin of these unisexual lineages requires an accurate understanding of species boundaries among gonochoristic whiptails. Doing so has historically been an extremely challenging problem which, in part, may be a consequence of widespread hybridization and incomplete reproductive isolation among lineages. The lack of a robust phylogenetic framework and uncertainty in species boundaries precludes studies of general patterns and mechanisms of introgression among whiptail species. Here, we use genomic data to reconstruct a robust estimate of evolutionary history in the largest clade of whiptail lizards (A. sexlineatus species group) and use it to identify patterns of introgression. Our results indicate substantial introgressive hybridization and admixture has occurred among multiple lineages of whiptails across diverse evolutionary time scales, and illustrate their impact on phylogenetic inference. Thus, hybridization among whiptail species appears to have been a prominent feature throughout their evolutionary history, which could, in part, explain why parthenogenesis has evolved so many times in whiptails in comparison to other vertebrate groups.}, } @article {pmid30562609, year = {2019}, author = {Silveira, TCD and Martins, MLL and Rody, HVS and Oliveira, LO}, title = {Evolutionary history of Manihot carthagenensis (Euphorbiaceae) and allied species in eastern South America.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {207-218}, doi = {10.1016/j.ympev.2018.12.017}, pmid = {30562609}, issn = {1095-9513}, abstract = {Intermittent episodes of climate changes, such as those that occurred during the Pleistocene, likely shaped the diversification of the young genus Manihot Mill. (Euphorbiacheae). One of such recently-derived congeners ─ M. carthagenensis ─ exhibits a widely disjunct distribution across dry environments in Eastern South America. Herein, we used molecular data from four nuclear gene regions (sts, ch_metE, g3pdh, and nia-i3) and seven nuclear microsatellite loci for reconstructing the phylogenetic relationships among M. carthagenensis and allied species and exploring likely phylogeographic scenarios that shaped the diversification and the distribution of gene pools of M. carthagenensis across the Caatinga and Chaco. Our data suggest that M. carthagenensis is not a monophyletic clade, as presently circumscribed. Morphological differences, genealogical relationships, and vegetation associations support three well-differentiated lineages, each of which merits the species rank: M. carthagenensis, M. glaziovii, and M. hahnii. Microsatellite data suggest that the newly circumscribed M. carthagenensis consists of at least three distinct gene pools, which are partly structured according to geography. The three gene pools likely evolved in allopatry, but remained interfertile. Population expansions after climate amelioration contributed to structuring hybrid zones. Moreover, we described two new single-copy gene regions (sts and ch_metE) as sources of molecular variation; they can facilitate the fine-scale probing of other parts of the phylogeny across Manihot.}, } @article {pmid30562487, year = {2019}, author = {Rasiah, PK and Maddala, R and Bennett, V and Rao, PV}, title = {Ankyrin-G regulated epithelial phenotype is required for mouse lens morphogenesis and growth.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {119-131}, doi = {10.1016/j.ydbio.2018.12.016}, pmid = {30562487}, issn = {1095-564X}, abstract = {Epithelial cell polarity, adhesion, proliferation, differentiation and survival are essential for morphogenesis of various organs and tissues including the ocular lens. The molecular mechanisms regulating the lens epithelial phenotype however, are not well understood. Here we investigated the role of scaffolding protein ankyrin-G (AnkG) in mouse lens development by conditional suppression of AnkG expression using the Cre-LoxP recombination approach. AnkG, which serves to link integral membrane proteins to the spectrin/actin cytoskeleton, was found to distribute predominantly to the lateral membranes of lens epithelium with several isoforms of the protein being detected in the mouse lens. Conditional deficiency of AnkG impaired mouse lens morphogenesis starting from embryonic stage E15.5, with neonatal (P1) AnkG cKO lenses exhibiting overt abnormalities in shape, size, epithelial cell height, sheet length and lateral membrane assembly together with defective fiber cell orientation relative to lenses from littermate AnkG floxed or Cre expressing mice. Severe disruptions in E-cadherin/β-catenin-based adherens junctions, and the membrane organization of spectrin-actin cytoskeleton, ZO-1, connexin-50 and Na+-K+-ATPase were noted in AnkG deficient lenses, along with detection in lens epithelium of α-smooth muscle actin, a marker of epithelial to mesenchymal transition. Moreover, lens epithelial cell proliferation and survival were severely compromised while differentiation appears to be normal in AnkG deficient mouse lenses. Collectively, these results indicate that AnkG regulates establishment of the epithelial phenotype via lateral membrane assembly, stabilization of E-cadherin-based cell-cell junctions, polarity and membrane organization of transport and adhesion proteins and the spectrin-actin skeleton, and provide evidence for an obligatory role for AnkG in lens morphogenesis and growth.}, } @article {pmid30562039, year = {2019}, author = {Gülzow, N and Wahlen, Y and Hillebrand, H}, title = {Metaecosystem Dynamics of Marine Phytoplankton Alters Resource Use Efficiency along Stoichiometric Gradients.}, journal = {The American naturalist}, volume = {193}, number = {1}, pages = {35-50}, doi = {10.1086/700835}, pmid = {30562039}, issn = {1537-5323}, abstract = {Metaecosystem theory addresses the link between local (within habitats) and regional (between habitats) dynamics by simultaneously analyzing spatial community ecology and abiotic matter flow. Here we experimentally address how spatial resource gradients and connectivity affect resource use efficiency (RUE) and stoichiometry in marine phytoplankton as well as the community composition at local and regional scales. We created gradostat metaecosystems consisting of five linearly interconnected patches, which were arranged either in countercurrent gradients of nitrogen (N) and phosphorus (P) supply or with a uniform spatial distribution of nutrients and which had either low or high connectivity. Gradient metaecosystems were characterized by higher remaining N and P concentrations (and N∶P ratios) than uniform ones, a difference reduced by higher connectivity. The position of the patch in the gradient strongly constrained elemental stoichiometry, local biovolume production, and RUE. As expected, algal carbon (C)∶N, biovolume, and N-specific RUE decreased toward the N-rich end of the gradient metaecosystem, whereas the opposite was observed for most of the gradient for C∶P, N∶P, and P-specific RUE. However, at highest N∶P supply, unexpectedly low C∶P, N∶P, and P-specific RUE values were found, indicating that the low availability of P inhibited efficient use of N and biovolume production. Consequently, gradient metaecosystems had lower overall biovolume at the regional scale. Whereas treatment effects on local richness were weak, gradients were characterized by higher dissimilarity in species composition. Thus, the stoichiometry of resource supply and spatial connectivity between patches appeared as decisive elements constraining phytoplankton composition and functioning in metaecosystems.}, } @article {pmid30561095, year = {2018}, author = {Temple, DH}, title = {Bioarchaeological evidence for adaptive plasticity and constraint: Exploring life-history trade-offs in the human past.}, journal = {Evolutionary anthropology}, volume = {}, number = {}, pages = {}, doi = {10.1002/evan.21754}, pmid = {30561095}, issn = {1520-6505}, support = {BCS 104490//National Science Foundation/ ; 104490//National Science Foundation/ ; 07318//Wenner Gren Foundation for Anthropological Research/ ; 07135//Wenner Gren Foundation for Anthropological Research/ ; 07012//Japan Society for the Promotion of Science/ ; }, abstract = {The Developmental Origins of Health and Disease paradigm evaluates the consequences of early life stress on health at later stages of life. Interacting with this paradigm represents a profound opportunity to leverage the lifespan and contextual approaches to human skeletal remains adopted by bioarchaeological research. Teeth and bone provide evidence for stressors experienced early in life. These events represent evidence for adaptive plasticity as Individuals survive the events through reallocation of energy to essential physiological functions, which inhibits enamel and skeletal growth. Age-at-death, adult body size, chronic infection, or childhood mortality may be used as covariates to better understand the physiological constraints operating on individual bodies following survival of early life stress. Contextual evidence from cemeteries provides clues to the ecological and cultural contingencies that exacerbate or mitigate the expression of these trade-offs. Future studies should incorporate newly derived methods that provide reproducible and precise ways to evaluate early life stress, while incorporating populations that are often neglected.}, } @article {pmid30560991, year = {2018}, author = {Burns, MD and Sidlauskas, BL}, title = {Ancient and contingent body shape diversification in a hyperdiverse continental fish radiation.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13658}, pmid = {30560991}, issn = {1558-5646}, support = {1257898//Division of Environmental Biology/ ; 0905606//Division of Emerging Frontiers/ ; }, abstract = {The characiform fishes of the Neotropics and Africa radiated remarkably in ecomorphology, but the macroevolutionary processes responsible for their biodiversity remain unexplored, and the degree to which their continental diversification parallels classic adaptive radiations remains untested. We reconstruct their diversification using a new fossil-calibrated molecular phylogeny, dietary information, and geometric morphometrics. Though body shape diversified early in a manner consistent with an ancient continental adaptive radiation, trophic shifts did not always coincide with shape changes. With the notable exception of piscivores, lineages that converged in diet did not converge closely in body shape. Shifts in habitat or other variables likely influenced body shape evolution in addition to changes in diet, and the clade's history departs from many classic adaptive radiations in lakes or on islands, in which trophic convergence drives morphological convergence. The contrast between the Neotropical radiation's exhaustive exploration of morphospace and the more restrained diversification in Africa suggests a major role for contingency in characiform evolution, with the presence of cypriniform competitors in the Old World, but not the New, providing one possible explanation. Our results depict the clearest ecomorphological reconstruction to date for Characiformes and set the stage for studies further elucidating the processes underlying its diversification.}, } @article {pmid30560958, year = {2018}, author = {}, title = {Classical and quantum computers are vying for superiority.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {302}, doi = {10.1038/d41586-018-07801-3}, pmid = {30560958}, issn = {1476-4687}, } @article {pmid30560957, year = {2018}, author = {Kaslow, DC and Black, S and Bloom, DE and Datla, M and Salisbury, D and Rappuoli, R}, title = {Vaccine candidates for poor nations are going to waste.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {337-339}, doi = {10.1038/d41586-018-07758-3}, pmid = {30560957}, issn = {1476-4687}, mesh = {Child ; Cost Sharing/economics ; Developing Countries/*economics ; Drug Development/*economics/*trends ; Drug Industry/economics ; Global Health/economics/trends ; Humans ; Malaria Vaccines/administration & dosage/economics ; Stakeholder Participation ; Vaccination/economics/trends ; Vaccines/*administration & dosage/*economics/supply & distribution ; }, } @article {pmid30560956, year = {2018}, author = {Abbott, A and Callaway, E and Castelvecchi, D and Else, H and Gibney, E and Ledford, H and Lee, JJ and Morello, L and Tollefson, J and Witze, A}, title = {2018 in news: The science events that shaped the year.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {314-317}, doi = {10.1038/d41586-018-07685-3}, pmid = {30560956}, issn = {1476-4687}, } @article {pmid30560955, year = {2018}, author = {Knosalla, C}, title = {Success for pig-to-baboon heart transplants.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {352-353}, doi = {10.1038/d41586-018-07419-5}, pmid = {30560955}, issn = {1476-4687}, mesh = {Animals ; Heart ; Heart Transplantation ; Heterografts ; *Papio ; Swine ; *Transplantation, Heterologous ; }, } @article {pmid30560366, year = {2019}, author = {Silva, PLAPA and Goulart, LR and Reis, TFM and Mendonça, EP and Melo, RT and Penha, VAS and Peres, PABM and Hoepers, PG and Beletti, ME and Fonseca, BB}, title = {Biofilm Formation in Different Salmonella Serotypes Isolated from Poultry.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {124-129}, doi = {10.1007/s00284-018-1599-5}, pmid = {30560366}, issn = {1432-0991}, support = {APQ03613-17//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; 465669/2014-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, abstract = {Little is known about Salmonella biofilm assembly, making the prevention of the disease a challenge in the poultry production chain. The objective of the present study was then to evaluate biofilm formation from different serotypes of Salmonella spp. in both polystyrene plates and eggshells. Salmonella Gallinarum and S. Minnesota were both classified as producers of biofilms of moderate intensity. Interestingly, S. Gallinarum produces biofilm even though being a serotype without flagellum and not having the lux gene in its genome, suggesting that there might be other important structures and genes associated with biofilm formation. Regarding Enteritidis, Typhimurium, Typhimurium variant, and Heidelberg serotypes, despite having high counts, BFI (Biofilm Formation Index) showed low biofilm production, probably due to the scarcity of extracellular matrix produced by such strains. A turkey eggshell model was then used for S. Enteritidis and S. Heidelberg biofilm formation. The results from the microbial count and scanning electron microscopy showed that Salmonella serotypes were also able to generate biofilm in eggshells, suggesting the presence of biofilms in poultry producing farms, a main concern for the poultry production industry.}, } @article {pmid30559593, year = {2018}, author = {Jiang, H and Lin, L and Tang, W and Chen, X and Zheng, Q and Huang, J and Yang, T and Su, L and Dong, Y and Wang, B and Wang, Z}, title = {Putative Interaction Proteins of the Ubiquitin Ligase Hrd1 in Magnaporthe oryzae.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318810990}, doi = {10.1177/1176934318810990}, pmid = {30559593}, issn = {1176-9343}, abstract = {The endoplasmic reticulum (ER) is the entry portal of the conventional secretory pathway where the newly synthesized polypeptides fold, modify, and assemble. The ER responses to the unfolded proteins in its lumen (ER stress) by triggering intracellular signal transduction pathways include the ER-associated degradation (ERAD) pathway and the unfolded protein response (UPR) pathway. In yeast and mammals, the ubiquitin ligase Hrd1 is indispensable for the ERAD pathway, and also Hrd1-mediated ERAD pathway plays a crucial role in maintaining homeostasis and metabolism of human beings. However, the underlying physiological roles and regulatory mechanism of the Hrd1-involved ERAD pathway in the plant pathogenic fungi are still unclear. Here, we identified the Hrd1 orthologous proteins from 9 different fungi and noticed that these Hrd1 orthologs are conserved. Through identification of MoHrd1 putative interacting proteins by co-immunoprecipitation assays and enrichment analysis, we found that MoHrd1 is involved in the secretory pathway, energy synthesis, and metabolism. Taken together, our results suggest that MoHrd1 is conserved among fungi and play an important role in cellular metabolism and infection-related development. Our finding helps uncover the mechanism of Hrd1-involved ERAD pathway in fungi and sheds a new light to understand the pathogenic mechanism of Magnaporthe oryzae.}, } @article {pmid30559490, year = {2019}, author = {Gulko, B and Siepel, A}, title = {An evolutionary framework for measuring epigenomic information and estimating cell-type-specific fitness consequences.}, journal = {Nature genetics}, volume = {51}, number = {2}, pages = {335-342}, doi = {10.1038/s41588-018-0300-z}, pmid = {30559490}, issn = {1546-1718}, support = {R01 GM102192/GM/NIGMS NIH HHS/United States ; R35 GM127070/GM/NIGMS NIH HHS/United States ; }, abstract = {Here we ask the question "How much information do epigenomic datasets provide about human genomic function?" We consider nine epigenomic features across 115 cell types and measure information about function as a reduction in entropy under a probabilistic evolutionary model fitted to human and nonhuman primate genomes. Several epigenomic features yield more information in combination than they do individually. We find that the entropy in human genetic variation predominantly reflects a balance between mutation and neutral drift. Our cell-type-specific FitCons scores reveal relationships among cell types and suggest that around 8% of nucleotide sites are constrained by natural selection.}, } @article {pmid30559489, year = {2019}, author = {Shema, E and Bernstein, BE and Buenrostro, JD}, title = {Single-cell and single-molecule epigenomics to uncover genome regulation at unprecedented resolution.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {19-25}, doi = {10.1038/s41588-018-0290-x}, pmid = {30559489}, issn = {1546-1718}, abstract = {Recent advances in single-cell and single-molecule epigenomic technologies now enable the study of genome regulation and dynamics at unprecedented resolution. In this Perspective, we highlight some of these transformative technologies and discuss how they have been used to identify new modes of gene regulation. We also contrast these assays with recent advances in single-cell transcriptomics and argue for the essential role of epigenomic technologies in both understanding cellular diversity and discovering gene regulatory mechanisms. In addition, we provide our view on the next generation of biological tools that we expect will open new avenues for elucidating the fundamental principles of gene regulation. Overall, this Perspective motivates the use of these high-resolution epigenomic technologies for mapping cell states and understanding regulatory diversity at single-molecule resolution within single cells.}, } @article {pmid30559488, year = {2019}, author = {Coe, BP and Stessman, HAF and Sulovari, A and Geisheker, MR and Bakken, TE and Lake, AM and Dougherty, JD and Lein, ES and Hormozdiari, F and Bernier, RA and Eichler, EE}, title = {Neurodevelopmental disease genes implicated by de novo mutation and copy number variation morbidity.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {106-116}, doi = {10.1038/s41588-018-0288-4}, pmid = {30559488}, issn = {1546-1718}, support = {//Howard Hughes Medical Institute/United States ; R01 MH101221/MH/NIMH NIH HHS/United States ; R01 MH107515/MH/NIMH NIH HHS/United States ; }, abstract = {We combined de novo mutation (DNM) data from 10,927 individuals with developmental delay and autism to identify 253 candidate neurodevelopmental disease genes with an excess of missense and/or likely gene-disruptive (LGD) mutations. Of these genes, 124 reach exome-wide significance (P < 5 × 10-7) for DNM. Intersecting these results with copy number variation (CNV) morbidity data shows an enrichment for genomic disorder regions (30/253, likelihood ratio (LR) +1.85, P = 0.0017). We identify genes with an excess of missense DNMs overlapping deletion syndromes (for example, KIF1A and the 2q37 deletion) as well as duplication syndromes, such as recurrent MAPK3 missense mutations within the chromosome 16p11.2 duplication, recurrent CHD4 missense DNMs in the 12p13 duplication region, and recurrent WDFY4 missense DNMs in the 10q11.23 duplication region. Network analyses of genes showing an excess of DNMs highlights functional networks, including cell-specific enrichments in the D1+ and D2+ spiny neurons of the striatum.}, } @article {pmid30559407, year = {2018}, author = {Vatanen, T and Plichta, DR and Somani, J and Münch, PC and Arthur, TD and Hall, AB and Rudolf, S and Oakeley, EJ and Ke, X and Young, RA and Haiser, HJ and Kolde, R and Yassour, M and Luopajärvi, K and Siljander, H and Virtanen, SM and Ilonen, J and Uibo, R and Tillmann, V and Mokurov, S and Dorshakova, N and Porter, JA and McHardy, AC and Lähdesmäki, H and Vlamakis, H and Huttenhower, C and Knip, M and Xavier, RJ}, title = {Genomic variation and strain-specific functional adaptation in the human gut microbiome during early life.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-018-0321-5}, pmid = {30559407}, issn = {2058-5276}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; }, abstract = {The human gut microbiome matures towards the adult composition during the first years of life and is implicated in early immune development. Here, we investigate the effects of microbial genomic diversity on gut microbiome development using integrated early childhood data sets collected in the DIABIMMUNE study in Finland, Estonia and Russian Karelia. We show that gut microbial diversity is associated with household location and linear growth of children. Single nucleotide polymorphism- and metagenomic assembly-based strain tracking revealed large and highly dynamic microbial pangenomes, especially in the genus Bacteroides, in which we identified evidence of variability deriving from Bacteroides-targeting bacteriophages. Our analyses revealed functional consequences of strain diversity; only 10% of Finnish infants harboured Bifidobacterium longum subsp. infantis, a subspecies specialized in human milk metabolism, whereas Russian infants commonly maintained a probiotic Bifidobacterium bifidum strain in infancy. Groups of bacteria contributing to diverse, characterized metabolic pathways converged to highly subject-specific configurations over the first two years of life. This longitudinal study extends the current view of early gut microbial community assembly based on strain-level genomic variation.}, } @article {pmid30559406, year = {2018}, author = {Kintses, B and Méhi, O and Ari, E and Számel, M and Györkei, Á and Jangir, PK and Nagy, I and Pál, F and Fekete, G and Tengölics, R and Nyerges, Á and Likó, I and Bálint, A and Molnár, T and Bálint, B and Vásárhelyi, BM and Bustamante, M and Papp, B and Pál, C}, title = {Phylogenetic barriers to horizontal transfer of antimicrobial peptide resistance genes in the human gut microbiota.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-018-0313-5}, pmid = {30559406}, issn = {2058-5276}, abstract = {The human gut microbiota has adapted to the presence of antimicrobial peptides (AMPs), which are ancient components of immune defence. Despite its medical importance, it has remained unclear whether AMP resistance genes in the gut microbiome are available for genetic exchange between bacterial species. Here, we show that AMP resistance and antibiotic resistance genes differ in their mobilization patterns and functional compatibilities with new bacterial hosts. First, whereas AMP resistance genes are widespread in the gut microbiome, their rate of horizontal transfer is lower than that of antibiotic resistance genes. Second, gut microbiota culturing and functional metagenomics have revealed that AMP resistance genes originating from phylogenetically distant bacteria have only a limited potential to confer resistance in Escherichia coli, an intrinsically susceptible species. Taken together, functional compatibility with the new bacterial host emerges as a key factor limiting the genetic exchange of AMP resistance genes. Finally, our results suggest that AMPs induce highly specific changes in the composition of the human microbiota, with implications for disease risks.}, } @article {pmid30559380, year = {2019}, author = {Ishizuka, JJ and Manguso, RT and Cheruiyot, CK and Bi, K and Panda, A and Iracheta-Vellve, A and Miller, BC and Du, PP and Yates, KB and Dubrot, J and Buchumenski, I and Comstock, DE and Brown, FD and Ayer, A and Kohnle, IC and Pope, HW and Zimmer, MD and Sen, DR and Lane-Reticker, SK and Robitschek, EJ and Griffin, GK and Collins, NB and Long, AH and Doench, JG and Kozono, D and Levanon, EY and Haining, WN}, title = {Loss of ADAR1 in tumours overcomes resistance to immune checkpoint blockade.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {43-48}, doi = {10.1038/s41586-018-0768-9}, pmid = {30559380}, issn = {1476-4687}, abstract = {Most patients with cancer either do not respond to immune checkpoint blockade or develop resistance to it, often because of acquired mutations that impair antigen presentation. Here we show that loss of function of the RNA-editing enzyme ADAR1 in tumour cells profoundly sensitizes tumours to immunotherapy and overcomes resistance to checkpoint blockade. In the absence of ADAR1, A-to-I editing of interferon-inducible RNA species is reduced, leading to double-stranded RNA ligand sensing by PKR and MDA5; this results in growth inhibition and tumour inflammation, respectively. Loss of ADAR1 overcomes resistance to PD-1 checkpoint blockade caused by inactivation of antigen presentation by tumour cells. Thus, effective anti-tumour immunity is constrained by inhibitory checkpoints such as ADAR1 that limit the sensing of innate ligands. The induction of sufficient inflammation in tumours that are sensitized to interferon can bypass the therapeutic requirement for CD8+ T cell recognition of cancer cells and may provide a general strategy to overcome immunotherapy resistance.}, } @article {pmid30559379, year = {2019}, author = {Ma, Q and Xu, SY and Shen, H and MacNeill, D and Fatemi, V and Chang, TR and Mier Valdivia, AM and Wu, S and Du, Z and Hsu, CH and Fang, S and Gibson, QD and Watanabe, K and Taniguchi, T and Cava, RJ and Kaxiras, E and Lu, HZ and Lin, H and Fu, L and Gedik, N and Jarillo-Herrero, P}, title = {Observation of the nonlinear Hall effect under time-reversal-symmetric conditions.}, journal = {Nature}, volume = {565}, number = {7739}, pages = {337-342}, doi = {10.1038/s41586-018-0807-6}, pmid = {30559379}, issn = {1476-4687}, abstract = {The electrical Hall effect is the production, upon the application of an electric field, of a transverse voltage under an out-of-plane magnetic field. Studies of the Hall effect have led to important breakthroughs, including the discoveries of Berry curvature and topological Chern invariants1,2. The internal magnetization of magnets means that the electrical Hall effect can occur in the absence of an external magnetic field2; this 'anomalous' Hall effect is important for the study of quantum magnets2-7. The electrical Hall effect has rarely been studied in non-magnetic materials without external magnetic fields, owing to the constraint of time-reversal symmetry. However, only in the linear response regime-when the Hall voltage is linearly proportional to the external electric field-does the Hall effect identically vanish as a result of time-reversal symmetry; the Hall effect in the nonlinear response regime is not subject to such symmetry constraints8-10. Here we report observations of the nonlinear Hall effect10 in electrical transport in bilayers of the non-magnetic quantum material WTe2 under time-reversal-symmetric conditions. We show that an electric current in bilayer WTe2 leads to a nonlinear Hall voltage in the absence of a magnetic field. The properties of this nonlinear Hall effect are distinct from those of the anomalous Hall effect in metals: the nonlinear Hall effect results in a quadratic, rather than linear, current-voltage characteristic and, in contrast to the anomalous Hall effect, the nonlinear Hall effect results in a much larger transverse than longitudinal voltage response, leading to a nonlinear Hall angle (the angle between the total voltage response and the applied electric field) of nearly 90 degrees. We further show that the nonlinear Hall effect provides a direct measure of the dipole moment10 of the Berry curvature, which arises from layer-polarized Dirac fermions in bilayer WTe2. Our results demonstrate a new type of Hall effect and provide a way of detecting Berry curvature in non-magnetic quantum materials.}, } @article {pmid30559378, year = {2019}, author = {Zhang, C and Zhang, Y and Yuan, X and Lu, S and Zhang, J and Narayan, A and Liu, Y and Zhang, H and Ni, Z and Liu, R and Choi, ES and Suslov, A and Sanvito, S and Pi, L and Lu, HZ and Potter, AC and Xiu, F}, title = {Quantum Hall effect based on Weyl orbits in Cd3As2.}, journal = {Nature}, volume = {565}, number = {7739}, pages = {331-336}, doi = {10.1038/s41586-018-0798-3}, pmid = {30559378}, issn = {1476-4687}, abstract = {Discovered decades ago, the quantum Hall effect remains one of the most studied phenomena in condensed matter physics and is relevant for research areas such as topological phases, strong electron correlations and quantum computing1-5. The quantized electron transport that is characteristic of the quantum Hall effect typically originates from chiral edge states-ballistic conducting channels that emerge when two-dimensional electron systems are subjected to large magnetic fields2. However, whether the quantum Hall effect can be extended to higher dimensions without simply stacking two-dimensional systems is unknown. Here we report evidence of a new type of quantum Hall effect, based on Weyl orbits in nanostructures of the three-dimensional topological semimetal Cd3As2. The Weyl orbits consist of Fermi arcs (open arc-like surface states) on opposite surfaces of the sample connected by one-dimensional chiral Landau levels along the magnetic field through the bulk6,7. This transport through the bulk results in an additional contribution (compared to stacked two-dimensional systems and which depends on the sample thickness) to the quantum phase of the Weyl orbit. Consequently, chiral states can emerge even in the bulk. To measure these quantum phase shifts and search for the associated chiral modes in the bulk, we conduct transport experiments using wedge-shaped Cd3As2 nanostructures with variable thickness. We find that the quantum Hall transport is strongly modulated by the sample thickness. The dependence of the Landau levels on the magnitude and direction of the magnetic field and on the sample thickness agrees with theoretical predictions based on the modified Lifshitz-Onsager relation for the Weyl orbits. Nanostructures of topological semimetals thus provide a way of exploring quantum Hall physics in three-dimensional materials with enhanced tunability.}, } @article {pmid30559360, year = {2018}, author = {Mitteroecker, P}, title = {How human bodies are evolving in modern societies.}, journal = {Nature ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41559-018-0773-2}, pmid = {30559360}, issn = {2397-334X}, } @article {pmid30559358, year = {2018}, author = {}, title = {Fossils tell a colourful tale.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {301-302}, doi = {10.1038/d41586-018-07800-4}, pmid = {30559358}, issn = {1476-4687}, } @article {pmid30559357, year = {2018}, author = {Reay, D}, title = {How I stave off despair as a climate scientist.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {303}, doi = {10.1038/d41586-018-07765-4}, pmid = {30559357}, issn = {1476-4687}, } @article {pmid30559356, year = {2018}, author = {Brown, A and Clardy, J}, title = {Tiny crystals have big potential for determining structures of small molecules.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {348-349}, doi = {10.1038/d41586-018-07756-5}, pmid = {30559356}, issn = {1476-4687}, } @article {pmid30559355, year = {2018}, author = {}, title = {Mini-tumours tell of immune cells' role in cancer.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {304}, doi = {10.1038/d41586-018-07752-9}, pmid = {30559355}, issn = {1476-4687}, } @article {pmid30559354, year = {2018}, author = {}, title = {A molecule that helps the 'exercise hormone' do its work.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {305}, doi = {10.1038/d41586-018-07711-4}, pmid = {30559354}, issn = {1476-4687}, } @article {pmid30559353, year = {2018}, author = {}, title = {Reptile urine used as paint in ancient Peru.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {305}, doi = {10.1038/d41586-018-07712-3}, pmid = {30559353}, issn = {1476-4687}, } @article {pmid30559352, year = {2018}, author = {}, title = {Dracula ant's powerful pincers snap shut at record speed.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {305}, doi = {10.1038/d41586-018-07710-5}, pmid = {30559352}, issn = {1476-4687}, } @article {pmid30559351, year = {2018}, author = {}, title = {The search for dark matter that runs on time.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {304-305}, doi = {10.1038/d41586-018-07698-y}, pmid = {30559351}, issn = {1476-4687}, } @article {pmid30559350, year = {2018}, author = {}, title = {How snuggling close affects bats' microbiome.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {304}, doi = {10.1038/d41586-018-07706-1}, pmid = {30559350}, issn = {1476-4687}, } @article {pmid30559349, year = {2018}, author = {}, title = {River bounces back after world's largest-ever dam removal.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {305}, doi = {10.1038/d41586-018-07707-0}, pmid = {30559349}, issn = {1476-4687}, } @article {pmid30559333, year = {2018}, author = {McDermott, GR and Meng, KC and McDonald, GG and Costello, CJ}, title = {Reply to Hanich et al.: Alternate explanations for the blue paradox do not withstand statistical scrutiny.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12124-E12125}, doi = {10.1073/pnas.1818687115}, pmid = {30559333}, issn = {1091-6490}, } @article {pmid30559331, year = {2018}, author = {Suwabe, K and Byun, K and Hyodo, K and Reagh, ZM and Roberts, JM and Matsushita, A and Saotome, K and Ochi, G and Fukuie, T and Suzuki, K and Sankai, Y and Yassa, MA and Soya, H}, title = {Reply to Gronwald et al.: Exercise intensity does indeed matter; maximal oxygen uptake is the gold-standard indicator.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11892-E11893}, doi = {10.1073/pnas.1818247115}, pmid = {30559331}, issn = {1091-6490}, mesh = {Dentate Gyrus ; *Exercise ; Gold ; Humans ; Oxygen ; *Oxygen Consumption ; }, } @article {pmid30559315, year = {2018}, author = {Hanich, Q and Rotjan, R and Aqorau, T and Bailey, M and Campbell, B and Gray, N and Gruby, R and Hampton, J and Ota, Y and Parris, H and Reid, C and Sumaila, UR and Swartz, W}, title = {Unraveling the blue paradox: Incomplete analysis yields incorrect conclusions about Phoenix Islands Protected Area closure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12122-E12123}, doi = {10.1073/pnas.1815600115}, pmid = {30559315}, issn = {1091-6490}, } @article {pmid30559215, year = {2019}, author = {Barton, RA and Montgomery, SH}, title = {Proportional versus relative size as metrics in human brain evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {3-4}, doi = {10.1073/pnas.1817200116}, pmid = {30559215}, issn = {1091-6490}, } @article {pmid30559214, year = {2019}, author = {Donahue, CJ and Glasser, MF and Preuss, TM and Rilling, JK and Van Essen, DC}, title = {Reply to Barton and Montgomery: A case for preferential prefrontal cortical expansion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {5-6}, doi = {10.1073/pnas.1819241116}, pmid = {30559214}, issn = {1091-6490}, support = {P51 OD011132/OD/NIH HHS/United States ; R24 NS092988/NS/NINDS NIH HHS/United States ; }, } @article {pmid30559213, year = {2018}, author = {Tedijanto, C and Olesen, SW and Grad, YH and Lipsitch, M}, title = {Estimating the proportion of bystander selection for antibiotic resistance among potentially pathogenic bacterial flora.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11988-E11995}, doi = {10.1073/pnas.1810840115}, pmid = {30559213}, issn = {1091-6490}, support = {R01 AI132606/AI/NIAID NIH HHS/United States ; U01 CK000538/CK/NCEZID CDC HHS/United States ; U01CK000538/ACL HHS/ACL HHS/United States ; U54 GM088558/GM/NIGMS NIH HHS/United States ; }, abstract = {Bystander selection-the selective pressure for resistance exerted by antibiotics on microbes that are not the target pathogen of treatment-is critical to understanding the total impact of broad-spectrum antibiotic use on pathogenic bacterial species that are often carried asymptomatically. However, to our knowledge, this effect has never been quantified. We quantify bystander selection for resistance for a range of clinically relevant antibiotic-species pairs as the proportion of all antibiotic exposures received by a species for conditions in which that species was not the causative pathogen ("proportion of bystander exposures"). Data sources include the 2010-2011 National Ambulatory Medical Care Survey and National Hospital Ambulatory Medical Care Survey, the Human Microbiome Project, and additional carriage and etiological data from existing literature. For outpatient prescribing in the United States, we find that this proportion over all included antibiotic classes is over 80% for eight of nine organisms of interest. Low proportions of bystander exposure are often associated with infrequent bacterial carriage or concentrated prescribing of a particular antibiotic for conditions caused by the species of interest. Applying our results, we roughly estimate that pneumococcal conjugate vaccination programs result in nearly the same proportional reduction in total antibiotic exposures of Streptococcus pneumoniae, Staphylococcus aureus, and Escherichia coli, despite the latter two organisms not being targeted by the vaccine. These results underscore the importance of considering antibiotic exposures of bystanders, in addition to the target pathogen, in measuring the impact of antibiotic resistance interventions.}, } @article {pmid30559212, year = {2019}, author = {Cordero-Herrera, I and Kozyra, M and Zhuge, Z and McCann Haworth, S and Moretti, C and Peleli, M and Caldeira-Dias, M and Jahandideh, A and Huirong, H and Cruz, JC and Kleschyov, AL and Montenegro, MF and Ingelman-Sundberg, M and Weitzberg, E and Lundberg, JO and Carlstrom, M}, title = {AMP-activated protein kinase activation and NADPH oxidase inhibition by inorganic nitrate and nitrite prevent liver steatosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {217-226}, doi = {10.1073/pnas.1809406115}, pmid = {30559212}, issn = {1091-6490}, abstract = {Advanced age and unhealthy dietary habits contribute to the increasing incidence of obesity and type 2 diabetes. These metabolic disorders, which are often accompanied by oxidative stress and compromised nitric oxide (NO) signaling, increase the risk of adverse cardiovascular complications and development of fatty liver disease. Here, we investigated the therapeutic effects of dietary nitrate, which is found in high levels in green leafy vegetables, on liver steatosis associated with metabolic syndrome. Dietary nitrate fuels a nitrate-nitrite-NO signaling pathway, which prevented many features of metabolic syndrome and liver steatosis that developed in mice fed a high-fat diet, with or without combination with an inhibitor of NOS (l-NAME). These favorable effects of nitrate were absent in germ-free mice, demonstrating the central importance of host microbiota in bioactivation of nitrate. In a human liver cell line (HepG2) and in a validated hepatic 3D model with primary human hepatocyte spheroids, nitrite treatment reduced the degree of metabolically induced steatosis (i.e., high glucose, insulin, and free fatty acids), as well as drug-induced steatosis (i.e., amiodarone). Mechanistically, the salutary metabolic effects of nitrate and nitrite can be ascribed to nitrite-derived formation of NO species and activation of soluble guanylyl cyclase, where xanthine oxidoreductase is proposed to mediate the reduction of nitrite. Boosting this nitrate-nitrite-NO pathway results in attenuation of NADPH oxidase-derived oxidative stress and stimulation of AMP-activated protein kinase and downstream signaling pathways regulating lipogenesis, fatty acid oxidation, and glucose homeostasis. These findings may have implications for novel nutrition-based preventive and therapeutic strategies against liver steatosis associated with metabolic dysfunction.}, } @article {pmid30559211, year = {2019}, author = {Shao, Y and Sun, Z and Wang, Y and Xu, C and Sankar, R and Breindel, AJ and Cao, C and Fogler, MM and Millis, AJ and Chou, F and Li, Z and Timusk, T and Maple, MB and Basov, DN}, title = {Optical signatures of Dirac nodal lines in NbAs2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {4}, pages = {1168-1173}, doi = {10.1073/pnas.1809631115}, pmid = {30559211}, issn = {1091-6490}, abstract = {Using polarized optical and magneto-optical spectroscopy, we have demonstrated universal aspects of electrodynamics associated with Dirac nodal lines that are found in several classes of unconventional intermetallic compounds. We investigated anisotropic electrodynamics of [Formula: see text] where the spin-orbit coupling (SOC) triggers energy gaps along the nodal lines. These gaps manifest as sharp steps in the optical conductivity spectra [Formula: see text] This behavior is followed by the linear power-law scaling of [Formula: see text] at higher frequencies, consistent with our theoretical analysis for dispersive Dirac nodal lines. Magneto-optics data affirm the dominant role of nodal lines in the electrodynamics of [Formula: see text].}, } @article {pmid30559210, year = {2019}, author = {Kobold, S}, title = {Innate and adaptive immunity combined for cancer treatment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {4}, pages = {1087-1088}, doi = {10.1073/pnas.1820166116}, pmid = {30559210}, issn = {1091-6490}, } @article {pmid30559209, year = {2019}, author = {McCready, AR and Paczkowski, JE and Henke, BR and Bassler, BL}, title = {Structural determinants driving homoserine lactone ligand selection in the Pseudomonas aeruginosa LasR quorum-sensing receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {245-254}, doi = {10.1073/pnas.1817239116}, pmid = {30559209}, issn = {1091-6490}, abstract = {Quorum sensing is a cell-cell communication process that bacteria use to orchestrate group behaviors. Quorum sensing is mediated by signal molecules called autoinducers. Autoinducers are often structurally similar, raising questions concerning how bacteria distinguish among them. Here, we use the Pseudomonas aeruginosa LasR quorum-sensing receptor to explore signal discrimination. The cognate autoinducer, 3OC12 homoserine lactone (3OC12HSL), is a more potent activator of LasR than other homoserine lactones. However, other homoserine lactones can elicit LasR-dependent quorum-sensing responses, showing that LasR displays ligand promiscuity. We identify mutants that alter which homoserine lactones LasR detects. Substitution at residue S129 decreases the LasR response to 3OC12HSL, while enhancing discrimination against noncognate autoinducers. Conversely, the LasR L130F mutation increases the potency of 3OC12HSL and other homoserine lactones. We solve crystal structures of LasR ligand-binding domains complexed with noncognate autoinducers. Comparison with existing structures reveals that ligand selectivity/sensitivity is mediated by a flexible loop near the ligand-binding site. We show that LasR variants with modified ligand preferences exhibit altered quorum-sensing responses to autoinducers in vivo. We suggest that possessing some ligand promiscuity endows LasR with the ability to optimally regulate quorum-sensing traits.}, } @article {pmid30559208, year = {2019}, author = {Song, H and Ou, W and Feng, Y and Zhang, J and Li, F and Hu, J and Peng, H and Xing, H and Ma, L and Tan, Q and Li, D and Wang, L and Wu, B and Shao, Y}, title = {Disparate impact on CD4 T cell count by two distinct HIV-1 phylogenetic clusters from the same clade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {239-244}, doi = {10.1073/pnas.1814714116}, pmid = {30559208}, issn = {1091-6490}, abstract = {HIV-1 evolved into various genetic subtypes and circulating recombinant forms (CRFs) in the global epidemic. The same subtype or CRF is usually considered to have similar phenotype. Being one of the world's major CRFs, CRF01_AE infection was reported to associate with higher prevalence of CXCR4 (X4) viruses and faster CD4 decline. However, the underlying mechanisms remain unclear. We identified eight phylogenetic clusters of CRF01_AE in China and hypothesized that they may have different phenotypes. In the National HIV Molecular Epidemiology Survey, we discovered that people infected by CRF01_AE cluster 4 had significantly lower CD4 counts (391 vs. 470, P < 0.0001) and higher prevalence of X4-using viruses (17.1% vs. 4.4%, P < 0.0001) compared with those infected by cluster 5. In an MSM cohort, X4-using viruses were only isolated from seroconvertors in cluster 4, which was associated with low a CD4 count within the first year of infection (141 vs. 440, P = 0.003). Using a coreceptor binding model, we identified unique V3 signatures in cluster 4 that favor CXCR4 use. We demonstrate that the HIV-1 phenotype and pathogenicity can be determined at the phylogenetic cluster level in the same subtype. Since its initial spread to humans from chimpanzees, estimated to be the first half of the 20th century, HIV-1 continues to undergo rapid evolution in larger and more diverse populations. The divergent phenotype evolution of two major CRF01_AE clusters highlights the importance of monitoring the genetic evolution and phenotypic shift of HIV-1 to provide early warning of the appearance of more pathogenic strains.}, } @article {pmid30559207, year = {2019}, author = {Chen, L and Singh, S and Kailath, T and Roychowdhury, V}, title = {Brain-inspired automated visual object discovery and detection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {96-105}, doi = {10.1073/pnas.1802103115}, pmid = {30559207}, issn = {1091-6490}, abstract = {Despite significant recent progress, machine vision systems lag considerably behind their biological counterparts in performance, scalability, and robustness. A distinctive hallmark of the brain is its ability to automatically discover and model objects, at multiscale resolutions, from repeated exposures to unlabeled contextual data and then to be able to robustly detect the learned objects under various nonideal circumstances, such as partial occlusion and different view angles. Replication of such capabilities in a machine would require three key ingredients: (i) access to large-scale perceptual data of the kind that humans experience, (ii) flexible representations of objects, and (iii) an efficient unsupervised learning algorithm. The Internet fortunately provides unprecedented access to vast amounts of visual data. This paper leverages the availability of such data to develop a scalable framework for unsupervised learning of object prototypes-brain-inspired flexible, scale, and shift invariant representations of deformable objects (e.g., humans, motorcycles, cars, airplanes) comprised of parts, their different configurations and views, and their spatial relationships. Computationally, the object prototypes are represented as geometric associative networks using probabilistic constructs such as Markov random fields. We apply our framework to various datasets and show that our approach is computationally scalable and can construct accurate and operational part-aware object models much more efficiently than in much of the recent computer vision literature. We also present efficient algorithms for detection and localization in new scenes of objects and their partial views.}, } @article {pmid30559206, year = {2019}, author = {Upadhya, D and Hattiangady, B and Castro, OW and Shuai, B and Kodali, M and Attaluri, S and Bates, A and Dong, Y and Zhang, SC and Prockop, DJ and Shetty, AK}, title = {Human induced pluripotent stem cell-derived MGE cell grafting after status epilepticus attenuates chronic epilepsy and comorbidities via synaptic integration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {287-296}, doi = {10.1073/pnas.1814185115}, pmid = {30559206}, issn = {1091-6490}, support = {IK6 BX003612/BX/BLRD VA/United States ; I01 BX000883/BX/BLRD VA/United States ; R24 NS086604/NS/NINDS NIH HHS/United States ; P50 MH100031/MH/NIMH NIH HHS/United States ; R01 NS096282/NS/NINDS NIH HHS/United States ; }, abstract = {Medial ganglionic eminence (MGE)-like interneuron precursors derived from human induced pluripotent stem cells (hiPSCs) are ideal for developing patient-specific cell therapy in temporal lobe epilepsy (TLE). However, their efficacy for alleviating spontaneous recurrent seizures (SRS) or cognitive, memory, and mood impairments has never been tested in models of TLE. Through comprehensive video- electroencephalographic recordings and a battery of behavioral tests in a rat model, we demonstrate that grafting of hiPSC-derived MGE-like interneuron precursors into the hippocampus after status epilepticus (SE) greatly restrained SRS and alleviated cognitive, memory, and mood dysfunction in the chronic phase of TLE. Graft-derived cells survived well, extensively migrated into different subfields of the hippocampus, and differentiated into distinct subclasses of inhibitory interneurons expressing various calcium-binding proteins and neuropeptides. Moreover, grafting of hiPSC-MGE cells after SE mediated several neuroprotective and antiepileptogenic effects in the host hippocampus, as evidenced by reductions in host interneuron loss, abnormal neurogenesis, and aberrant mossy fiber sprouting in the dentate gyrus (DG). Furthermore, axons from graft-derived interneurons made synapses on the dendrites of host excitatory neurons in the DG and the CA1 subfield of the hippocampus, implying an excellent graft-host synaptic integration. Remarkably, seizure-suppressing effects of grafts were significantly reduced when the activity of graft-derived interneurons was silenced by a designer drug while using donor hiPSC-MGE cells expressing designer receptors exclusively activated by designer drugs (DREADDs). These results implied the direct involvement of graft-derived interneurons in seizure control likely through enhanced inhibitory synaptic transmission. Collectively, the results support a patient-specific MGE cell grafting approach for treating TLE.}, } @article {pmid30559205, year = {2019}, author = {Townsend, GE and Han, W and Schwalm, ND and Raghavan, V and Barry, NA and Goodman, AL and Groisman, EA}, title = {Dietary sugar silences a colonization factor in a mammalian gut symbiont.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {233-238}, doi = {10.1073/pnas.1813780115}, pmid = {30559205}, issn = {1091-6490}, support = {R01 GM123798/GM/NIGMS NIH HHS/United States ; }, abstract = {The composition of the gut microbiota is largely determined by environmental factors including the host diet. Dietary components are believed to influence the composition of the gut microbiota by serving as nutrients to a subset of microbes, thereby favoring their expansion. However, we now report that dietary fructose and glucose, which are prevalent in the Western diet, specifically silence a protein that is necessary for gut colonization, but not for utilization of these sugars, by the human gut commensal Bacteroides thetaiotaomicron Silencing by fructose and glucose requires the 5' leader region of the mRNA specifying the protein, designated Roc for regulator of colonization. Incorporation of the roc leader mRNA in front of a heterologous gene was sufficient for fructose and glucose to turn off expression of the corresponding protein. An engineered strain refractory to Roc silencing by these sugars outcompeted wild-type B. thetaiotaomicron in mice fed a diet rich in glucose and sucrose (a disaccharide composed of glucose and fructose), but not in mice fed a complex polysaccharide-rich diet. Our findings underscore a role for dietary sugars that escape absorption by the host intestine and reach the microbiota: regulation of gut colonization by beneficial microbes independently of supplying nutrients to the microbiota.}, } @article {pmid30559204, year = {2018}, author = {Bloom, DE and Black, S and Salisbury, D and Rappuoli, R}, title = {Antimicrobial resistance and the role of vaccines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12868-12871}, doi = {10.1073/pnas.1717157115}, pmid = {30559204}, issn = {1091-6490}, } @article {pmid30559203, year = {2018}, author = {Sevilla, JP and Bloom, DE and Cadarette, D and Jit, M and Lipsitch, M}, title = {Toward economic evaluation of the value of vaccines and other health technologies in addressing AMR.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12911-12919}, doi = {10.1073/pnas.1717161115}, pmid = {30559203}, issn = {1091-6490}, support = {U54 GM088558/GM/NIGMS NIH HHS/United States ; R01 AI048935/AI/NIAID NIH HHS/United States ; }, abstract = {We discuss the need to make economic evaluations of vaccines antimicrobial resistance (AMR)-sensitive and ways to do so. Such AMR-sensitive evaluations can play a role in value-for-money comparisons of different vaccines within a national immunization program, or in comparisons of vaccine-centric and non-vaccine-centric technologies within an anti-AMR program. In general terms, incremental cost-effectiveness ratios and rates of return and their associated decision rules are unaltered by consideration of AMR-related value. The decision metrics need to have their various health, cost, and socioeconomic terms disaggregated into resistance-related subcategories, which in turn have to be measured carefully before they are reaggregated. The fundamental scientific challenges lie primarily in quantifying the causal impact of health technologies on resistance-related health outcomes, and secondarily in ascertaining the economic value of those outcomes. We emphasize the importance of evaluating vaccines in the context of other potentially complementary and substitutable nonvaccine technologies. Complementarity implies that optimal spending on each set of interventions is positive, and substitutability implies that the ratio of spending will depend on relative value for money. We exemplify this general point through a qualitative discussion of the complementarities and (especially the) substitutability between pneumococcal conjugate vaccines and antimicrobial stewardship and between research and development (R&D) of a gonorrhea vaccine versus R&D of a gonorrhea antibiotic. We propose a roadmap for future work, which includes quantifying the causal effects of vaccination and other health technologies on short-term and long-term resistance-related outcomes, measuring the health-sector costs and broader socioeconomic consequences of resistance-related mortality and morbidity, and evaluating vaccines in the context of nonvaccine complements and substitutes.}, } @article {pmid30559202, year = {2019}, author = {Zidi, B and Vincent-Fabert, C and Pouyet, L and Seillier, M and Vandevelde, A and N'guessan, P and Poplineau, M and Guittard, G and Mancini, SJC and Duprez, E and Carrier, A}, title = {TP53INP1 deficiency maintains murine B lymphopoiesis in aged bone marrow through redox-controlled IL-7R/STAT5 signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {211-216}, doi = {10.1073/pnas.1809980116}, pmid = {30559202}, issn = {1091-6490}, abstract = {Bone marrow (BM) produces all blood and immune cells deriving from hematopoietic stem cells (HSCs). The decrease of immune cell production during aging is one of the features of immunosenescence. The impact of redox dysregulation in BM aging is still poorly understood. Here we use TP53INP1-deficient (KO) mice endowed with chronic oxidative stress to assess the influence of aging-associated redox alterations in BM homeostasis. We show that TP53INP1 deletion has no impact on aging-related accumulation of HSCs. In contrast, the aging-related contraction of the lymphoid compartment is mitigated in TP53INP1 KO mice. B cells that accumulate in old KO BM are differentiating cells that can mature into functional B cells. Importantly, this phenotype results from B cell-intrinsic events associated with defective redox control. Finally, we show that oxidative stress in aged TP53INP1-deficient mice maintains STAT5 expression and activation in early B cells, driving high Pax5 expression, which provides a molecular mechanism for maintenance of B cell development upon aging.}, } @article {pmid30559201, year = {2019}, author = {Kluender, EJ and Hedrick, JL and Brown, KA and Rao, R and Meckes, B and Du, JS and Moreau, LM and Maruyama, B and Mirkin, CA}, title = {Catalyst discovery through megalibraries of nanomaterials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {40-45}, doi = {10.1073/pnas.1815358116}, pmid = {30559201}, issn = {1091-6490}, support = {U54 CA199091/CA/NCI NIH HHS/United States ; }, abstract = {The nanomaterial landscape is so vast that a high-throughput combinatorial approach is required to understand structure-function relationships. To address this challenge, an approach for the synthesis and screening of megalibraries of unique nanoscale features (>10,000,000) with tailorable location, size, and composition has been developed. Polymer pen lithography, a parallel lithographic technique, is combined with an ink spray-coating method to create pen arrays, where each pen has a different but deliberately chosen quantity and composition of ink. With this technique, gradients of Au-Cu bimetallic nanoparticles have been synthesized and then screened for activity by in situ Raman spectroscopy with respect to single-walled carbon nanotube (SWNT) growth. Au3Cu, a composition not previously known to catalyze SWNT growth, has been identified as the most active composition.}, } @article {pmid30559200, year = {2018}, author = {Klemm, EJ and Wong, VK and Dougan, G}, title = {Emergence of dominant multidrug-resistant bacterial clades: Lessons from history and whole-genome sequencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12872-12877}, doi = {10.1073/pnas.1717162115}, pmid = {30559200}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Antibiotic resistance in bacteria has emerged as a global challenge over the past 90 years, compromising our ability to effectively treat infections. There has been a dramatic increase in antibiotic resistance-associated determinants in bacterial populations, driven by the mobility and infectious nature of such determinants. Bacterial genome flexibility and antibiotic-driven selection are at the root of the problem. Genome evolution and the emergence of highly successful multidrug-resistant clades in different pathogens have made this a global challenge. Here, we describe some of the factors driving the origin, evolution, and spread of the antibiotic resistance genotype.}, } @article {pmid30559199, year = {2018}, author = {Kennedy, DA and Read, AF}, title = {Why the evolution of vaccine resistance is less of a concern than the evolution of drug resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12878-12886}, doi = {10.1073/pnas.1717159115}, pmid = {30559199}, issn = {1091-6490}, support = {R01 GM105244/GM/NIGMS NIH HHS/United States ; }, abstract = {Vaccines and antimicrobial drugs both impose strong selection for resistance. Yet only drug resistance is a major challenge for 21st century medicine. Why is drug resistance ubiquitous and not vaccine resistance? Part of the answer is that vaccine resistance is far less likely to evolve than drug resistance. But what happens when vaccine resistance does evolve? We review six putative cases. We find that in contrast to drug resistance, vaccine resistance is harder to detect and harder to confirm and that the mechanistic basis is less well understood. Nevertheless, in the cases we examined, the pronounced health benefits associated with vaccination have largely been sustained. Thus, we contend that vaccine resistance is less of a concern than drug resistance because it is less likely to evolve and when it does, it is less harmful to human and animal health and well-being. Studies of pathogen strains that evolve the capacity to replicate and transmit from vaccinated hosts will enhance our ability to develop next-generation vaccines that minimize the risk of harmful pathogen evolution.}, } @article {pmid30559198, year = {2019}, author = {Zalles, V and Hansen, MC and Potapov, PV and Stehman, SV and Tyukavina, A and Pickens, A and Song, XP and Adusei, B and Okpa, C and Aguilar, R and John, N and Chavez, S}, title = {Near doubling of Brazil's intensive row crop area since 2000.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {428-435}, doi = {10.1073/pnas.1810301115}, pmid = {30559198}, issn = {1091-6490}, abstract = {Brazil has become a global leader in the production of commodity row crops such as soybean, sugarcane, cotton, and corn. Here, we report an increase in Brazilian cropland extent from 26.0 Mha in 2000 to 46.1 Mha in 2014. The states of Maranhão, Tocantins, Piauí, Bahia (collectively MATOPIBA), Mato Grosso, Mato Grosso do Sul, and Pará all more than doubled in cropland extent. The states of Goiás, Minas Gerais, and São Paulo each experienced >50% increases. The vast majority of expansion, 79%, occurred on repurposed pasture lands, and 20% was from the conversion of natural vegetation. Area of converted Cerrado savannas was nearly 2.5 times that of Amazon forests, and accounted for more than half of new cropland in MATOPIBA. Spatiotemporal dynamics of cropland expansion reflect market conditions, land use policies, and other factors. Continued extensification of cropland across Brazil is possible and may be likely under current conditions, with attendant benefits for and challenges to development.}, } @article {pmid30559197, year = {2018}, author = {}, title = {Correction Rivas-Carrillo et al., Whole-genome comparison of endogenous retrovirus segregation across wild and domestic host species populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12465}, doi = {10.1073/pnas.1820237116}, pmid = {30559197}, issn = {1091-6490}, } @article {pmid30559196, year = {2019}, author = {Woodard, DL and Davis, SJ and Randerson, JT}, title = {Economic carbon cycle feedbacks may offset additional warming from natural feedbacks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {759-764}, doi = {10.1073/pnas.1805187115}, pmid = {30559196}, issn = {1091-6490}, abstract = {As the Earth warms, carbon sinks on land and in the ocean will weaken, thereby increasing the rate of warming. Although natural mechanisms contributing to this positive climate-carbon feedback have been evaluated using Earth system models, analogous feedbacks involving human activities have not been systematically quantified. Here we conceptualize and estimate the magnitude of several economic mechanisms that generate a carbon-climate feedback, using the Kaya identity to separate a net economic feedback into components associated with population, GDP, heating and cooling, and the carbon intensity of energy production and transportation. We find that climate-driven decreases in economic activity (GDP) may in turn decrease human energy use and thus fossil fuel CO2 emissions. In a high radiative forcing scenario, such decreases in economic activity reduce fossil fuel emissions by 13% this century, lowering atmospheric CO2 by over 100 ppm in 2100. The natural carbon-climate feedback, in contrast, increases atmospheric CO2 over this period by a similar amount, and thus, the net effect including both feedbacks is nearly zero. Our work highlights the importance of improving the representation of climate-economic feedbacks in scenarios of future change. Although the effects of climate warming on the economy may offset weakening land and ocean carbon sinks, a loss of economic productivity will have high societal costs, potentially increasing wealth inequity and limiting resources available for effective adaptation.}, } @article {pmid30559195, year = {2018}, author = {Klugman, KP and Black, S}, title = {Impact of existing vaccines in reducing antibiotic resistance: Primary and secondary effects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12896-12901}, doi = {10.1073/pnas.1721095115}, pmid = {30559195}, issn = {1091-6490}, abstract = {Vaccines impact antibiotic-resistant infections in two ways: through a direct reduction in the organisms and strains carrying resistant genes that are specifically targeted by the vaccine and also via a secondary effect through a reduction in febrile illnesses that often lead to the use of antibiotics. We review here the impact of pneumococcal conjugate vaccines (PCVs) on the prevalence of antibiotic-resistant disease and antibiotic usage as an example of the direct effect of vaccines on antibiotic resistance and the impact of influenza vaccination on antibiotic usage as an example of a secondary effect. A prelicensure study of a PCV in Africa demonstrated 67% fewer penicillin-resistant invasive disease episodes in the PCV group compared with controls. Similar studies in the United States and Europe demonstrated reductions in antibiotic use consistent with the vaccines' impact on the risk of otitis media infections in children. Postlicensure reductions in the circulation of antibiotic-resistant strains targeted by the vaccines have been dramatic, with virtual elimination of these strains in children following vaccine introduction. In terms of a secondary effect, following influenza vaccination reductions of 13-50% have been observed in the use of antibiotics by individuals receiving influenza vaccine compared with controls. With the demonstrated effectiveness of vaccination programs in impacting the risk of antibiotic-resistant infections and the increasing threat to public health that these infections represent, more attention needs to be given to development and utilization of vaccines to address antibiotic resistance.}, } @article {pmid30559194, year = {2019}, author = {Hofmann, R and Tietje, M and Aberhan, M}, title = {Diversity partitioning in Phanerozoic benthic marine communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {79-83}, doi = {10.1073/pnas.1814487116}, pmid = {30559194}, issn = {1091-6490}, abstract = {Biotic interactions such as competition, predation, and niche construction are fundamental drivers of biodiversity at the local scale, yet their long-term effect during earth history remains controversial. To test their role and explore potential limits to biodiversity, we determine within-habitat (alpha), between-habitat (beta), and overall (gamma) diversity of benthic marine invertebrates for Phanerozoic geological formations. We show that an increase in gamma diversity is consistently generated by an increase in alpha diversity throughout the Phanerozoic. Beta diversity drives gamma diversity only at early stages of diversification but remains stationary once a certain gamma level is reached. This mode is prevalent during early- to mid-Paleozoic periods, whereas coupling of beta and gamma diversity becomes increasingly weak toward the recent. Generally, increases in overall biodiversity were accomplished by adding more species to local habitats, and apparently this process never reached saturation during the Phanerozoic. Our results provide general support for an ecological model in which diversification occurs in successive phases of progressing levels of biotic interactions.}, } @article {pmid30559193, year = {2019}, author = {Majumder, P and Rudack, T and Beck, F and Danev, R and Pfeifer, G and Nagy, I and Baumeister, W}, title = {Cryo-EM structures of the archaeal PAN-proteasome reveal an around-the-ring ATPase cycle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {534-539}, doi = {10.1073/pnas.1817752116}, pmid = {30559193}, issn = {1091-6490}, abstract = {Proteasomes occur in all three domains of life, and are the principal molecular machines for the regulated degradation of intracellular proteins. They play key roles in the maintenance of protein homeostasis, and control vital cellular processes. While the eukaryotic 26S proteasome is extensively characterized, its putative evolutionary precursor, the archaeal proteasome, remains poorly understood. The primordial archaeal proteasome consists of a 20S proteolytic core particle (CP), and an AAA-ATPase module. This minimal complex degrades protein unassisted by non-ATPase subunits that are present in a 26S proteasome regulatory particle (RP). Using cryo-EM single-particle analysis, we determined structures of the archaeal CP in complex with the AAA-ATPase PAN (proteasome-activating nucleotidase). Five conformational states were identified, elucidating the functional cycle of PAN, and its interaction with the CP. Coexisting nucleotide states, and correlated intersubunit signaling features, coordinate rotation of the PAN-ATPase staircase, and allosterically regulate N-domain motions and CP gate opening. These findings reveal the structural basis for a sequential around-the-ring ATPase cycle, which is likely conserved in AAA-ATPases.}, } @article {pmid30559192, year = {2019}, author = {Zhang, Y and Zhang, J and Guo, J and Zhou, F and Singh, S and Xu, X and Xie, Q and Yang, Z and Huang, CF}, title = {F-box protein RAE1 regulates the stability of the aluminum-resistance transcription factor STOP1 in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {319-327}, doi = {10.1073/pnas.1814426116}, pmid = {30559192}, issn = {1091-6490}, abstract = {Aluminum (Al) toxicity is a major factor limiting crop production on acid soils, which represent over 30% of the world's arable land. Some plants have evolved mechanisms to detoxify Al. Arabidopsis, for example, secretes malate via the AtALMT1 transporter to chelate and detoxify Al. The C2H2-type transcription factor STOP1 plays a crucial role in Al resistance by inducing the expression of a set of genes, including AtALMT1 Here, we identify and characterize an F-box protein-encoding gene regulation of Atalmt1 expression 1 (RAE1) that regulates the level of STOP1. Mutation and overexpression of RAE1 increases or decreases the expression of AtALMT1 and other STOP1-regulated genes, respectively. RAE1 interacts with and promotes the degradation of STOP1 via the ubiquitin-26S proteasome pathway, while Al stress promotes the accumulation of STOP1. We find that STOP1 up-regulates RAE1 expression by directly binding to the RAE1 promoter, thus forming a negative feedback loop between STOP1 and RAE1. Our results demonstrate that RAE1 influences Al resistance through the ubiquitination and degradation of STOP1.}, } @article {pmid30559191, year = {2019}, author = {Duah, E and Teegala, LR and Kondeti, V and Adapala, RK and Keshamouni, VG and Kanaoka, Y and Austen, KF and Thodeti, CK and Paruchuri, S}, title = {Cysteinyl leukotriene 2 receptor promotes endothelial permeability, tumor angiogenesis, and metastasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {199-204}, doi = {10.1073/pnas.1817325115}, pmid = {30559191}, issn = {1091-6490}, abstract = {Cysteinyl leukotrienes (cys-LTs) are proinflammatory mediators that enhance vascular permeability through distinct receptors (CysLTRs). We found that CysLT2R regulates angiogenesis in isolated mouse endothelial cells (ECs) and in Matrigel implants in WT mice and enhances EC contraction and permeability via the Rho-dependent myosin light chain 2 and vascular endothelial (VE)-cadherin axis. Since solid tumors utilize aberrant angiogenesis for their growth and metastasis and their vessels exhibit vascular hyperpermeability, we hypothesized that CysLT2R, via its actions on the endothelium, might regulate tumor growth. Both tumor growth and metastases of adoptively transferred syngeneic Lewis lung carcinoma (LLC) cells are significantly reduced in CysLT2R-null mice (Cysltr2-/-) compared with WT and CysLT1R-null mice (Cysltr1-/-). In WT recipients of LLC cells, CysLT2R expression is significantly increased in the tumor vasculature, compared with CysLT1R. Further, the tumor vasculature in Cysltr2-/- recipients exhibited significantly improved integrity, as revealed by increased pericyte coverage and decreased leakage of i.v.-administered Texas Red-conjugated dextran. Administration of a selective CysLT2R antagonist significantly reduced LLC tumor volume, vessel density, dextran leakage, and metastases in WT mice, highlighting CysLT2R as a VEGF-independent regulator of the vasculature promoting risk of metastasis. Thus, both genetic and pharmacological findings establish CysLT2R as a gateway for angiogenesis and EC dysregulation in vitro and ex vivo and in an in vivo model with a mouse tumor. Our data suggest CysLT2R as a possible target for intervention.}, } @article {pmid30559190, year = {2019}, author = {Levi, SM and Li, Q and Rötheli, AR and Jacobsen, EN}, title = {Catalytic activation of glycosyl phosphates for stereoselective coupling reactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {35-39}, doi = {10.1073/pnas.1811186116}, pmid = {30559190}, issn = {1091-6490}, support = {R01 GM043214/GM/NIGMS NIH HHS/United States ; R37 GM043214/GM/NIGMS NIH HHS/United States ; U01 GM116249/GM/NIGMS NIH HHS/United States ; }, abstract = {Glycosyl phosphates are shown to be activated to stereospecific nucleophilic substitution reactions by precisely tailored bis-thiourea catalysts. Enhanced reactivity and scope is observed with phosphate relative to chloride leaving groups. Stronger binding (Km) to the H-bond donor and enhanced reactivity of the complex (kcat) enables efficient catalysis with broad functional group compatibility under mild, neutral conditions.}, } @article {pmid30559189, year = {2019}, author = {Birrane, G and Beigneux, AP and Dwyer, B and Strack-Logue, B and Kristensen, KK and Francone, OL and Fong, LG and Mertens, HDT and Pan, CQ and Ploug, M and Young, SG and Meiyappan, M}, title = {Structure of the lipoprotein lipase-GPIHBP1 complex that mediates plasma triglyceride hydrolysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {5}, pages = {1723-1732}, doi = {10.1073/pnas.1817984116}, pmid = {30559189}, issn = {1091-6490}, support = {P01 HL090553/HL/NHLBI NIH HHS/United States ; R01 HL087228/HL/NHLBI NIH HHS/United States ; R01 HL125335/HL/NHLBI NIH HHS/United States ; R35 HL139725/HL/NHLBI NIH HHS/United States ; }, abstract = {Lipoprotein lipase (LPL) is responsible for the intravascular processing of triglyceride-rich lipoproteins. The LPL within capillaries is bound to GPIHBP1, an endothelial cell protein with a three-fingered LU domain and an N-terminal intrinsically disordered acidic domain. Loss-of-function mutations in LPL or GPIHBP1 cause severe hypertriglyceridemia (chylomicronemia), but structures for LPL and GPIHBP1 have remained elusive. Inspired by our recent discovery that GPIHBP1's acidic domain preserves LPL structure and activity, we crystallized an LPL-GPIHBP1 complex and solved its structure. GPIHBP1's LU domain binds to LPL's C-terminal domain, largely by hydrophobic interactions. Analysis of electrostatic surfaces revealed that LPL contains a large basic patch spanning its N- and C-terminal domains. GPIHBP1's acidic domain was not defined in the electron density map but was positioned to interact with LPL's large basic patch, providing a likely explanation for how GPIHBP1 stabilizes LPL. The LPL-GPIHBP1 structure provides insights into mutations causing chylomicronemia.}, } @article {pmid30559188, year = {2019}, author = {Göbel, K and Asaridou, CM and Merker, M and Eichler, S and Herrmann, AM and Geuß, E and Ruck, T and Schüngel, L and Groeneweg, L and Narayanan, V and Schneider-Hohendorf, T and Gross, CC and Wiendl, H and Kehrel, BE and Kleinschnitz, C and Meuth, SG}, title = {Plasma kallikrein modulates immune cell trafficking during neuroinflammation via PAR2 and bradykinin release.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {271-276}, doi = {10.1073/pnas.1810020116}, pmid = {30559188}, issn = {1091-6490}, abstract = {Blood-brain barrier (BBB) disruption and transendothelial trafficking of immune cells into the central nervous system (CNS) are pathophysiological hallmarks of neuroinflammatory disorders like multiple sclerosis (MS). Recent evidence suggests that the kallikrein-kinin and coagulation system might participate in this process. Here, we identify plasma kallikrein (KK) as a specific direct modulator of BBB integrity. Levels of plasma prekallikrein (PK), the precursor of KK, were markedly enhanced in active CNS lesions of MS patients. Deficiency or pharmacologic blockade of PK renders mice less susceptible to experimental autoimmune encephalomyelitis (a model of MS) and is accompanied by a remarkable reduction of BBB disruption and CNS inflammation. In vitro analysis revealed that KK modulates endothelial cell function in a protease-activated receptor-2-dependent manner, leading to an up-regulation of the cellular adhesion molecules Intercellular Adhesion Molecule 1 and Vascular Cell Adhesion Molecule 1, thereby amplifying leukocyte trafficking. Our study demonstrates that PK is an important direct regulator of BBB integrity as a result of its protease function. Therefore, KK inhibition can decrease BBB damage and cell invasion during neuroinflammation and may offer a strategy for the treatment of MS.}, } @article {pmid30559187, year = {2018}, author = {Murphy, DM and Ravishankara, AR}, title = {Trends and patterns in the contributions to cumulative radiative forcing from different regions of the world.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13192-13197}, doi = {10.1073/pnas.1813951115}, pmid = {30559187}, issn = {1091-6490}, abstract = {Different regions of the world have had different historical patterns of emissions of carbon dioxide, other greenhouse gases, and aerosols as well as different land-use changes. One can estimate the net cumulative contribution by each region to the global mean radiative forcing due to past greenhouse gas emissions, aerosol precursors, and carbon dioxide from land-use changes. Several patterns stand out from such calculations. Some regions have had a common historical pattern in which the short-term offsets between the radiative forcings from carbon dioxide and sulfate aerosols temporarily led to near-zero radiative forcing during periods of exponential emissions growth with few emission controls. This happened for North America and Europe in the mid-20th century and China in the 1990s and 2000s. However, these same periods lead to a commitment to future radiative forcing from the carbon dioxide and other greenhouse gases that stay in the atmosphere long after the aerosols. For every region, this commitment to future radiative forcing (2018-2100) from emissions already in the atmosphere is larger than the cumulative radiative forcing to date (1900-2017). This comparison again highlights how the full radiative forcing from greenhouse gases is unmasked once the aerosol emissions are reduced to improve air quality. The relative contributions from various regions to global climate forcing depends more on the time the contributions are compared (e.g., now or 2100) and future development scenarios than on whether cumulative radiative forcing, ocean heat content, or temperature is used to compare regional contributions.}, } @article {pmid30559186, year = {2019}, author = {Wu, S and Song, W and Wong, CCL and Shi, Y}, title = {Bax inhibitor 1 is a γ-secretase-independent presenilin-binding protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {141-147}, doi = {10.1073/pnas.1810870116}, pmid = {30559186}, issn = {1091-6490}, abstract = {Presenilin is the catalytic subunit of γ-secretase, a four-component intramembrane protease responsible for the generation of β-amyloid (Aβ) peptides. Over 200 Alzheimer's disease-related mutations have been identified in presenilin 1 (PS1) and PS2. Here, we report that Bax-inhibitor 1 (BI1), an evolutionarily conserved transmembrane protein, stably associates with PS1. BI1 specifically interacts with PS1 in isolation, but not with PS1 in the context of an assembled γ-secretase. The PS1-BI1 complex exhibits no apparent proteolytic activity, as judged by the inability to produce Aβ40 and Aβ42 from the substrate APP-C99. At an equimolar concentration, BI1 has no impact on the proteolytic activity of γ-secretase; at a 200-fold molar excess, BI1 reduces γ-secretase activity nearly by half. Our biochemical study identified BI1 as a PS1-interacting protein, suggesting additional functions of PS1 beyond its involvement in γ-secretase.}, } @article {pmid30559185, year = {2018}, author = {}, title = {Correction for Kritee et al., Reply to Yan and Akiyama: Nitrous oxide emissions from rice and their mitigation potential depend on the nature of intermittent flooding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12463}, doi = {10.1073/pnas.1819938116}, pmid = {30559185}, issn = {1091-6490}, } @article {pmid30559184, year = {2019}, author = {Fukumoto, K and Fogaça, MV and Liu, RJ and Duman, C and Kato, T and Li, XY and Duman, RS}, title = {Activity-dependent brain-derived neurotrophic factor signaling is required for the antidepressant actions of (2R,6R)-hydroxynorketamine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {297-302}, doi = {10.1073/pnas.1814709116}, pmid = {30559184}, issn = {1091-6490}, support = {R01 MH093897/MH/NIMH NIH HHS/United States ; R01 MH105910/MH/NIMH NIH HHS/United States ; }, abstract = {Ketamine, a noncompetitive N-methyl-d-aspartate (NMDA) receptor antagonist, produces rapid and long-lasting antidepressant effects in major depressive disorder (MDD) patients. (2R,6R)-Hydroxynorketamine [(2R,6R)-HNK], a metabolite of ketamine, is reported to produce rapid antidepressant effects in rodent models without the side effects of ketamine. Importantly, (2R,6R)-HNK does not block NMDA receptors like ketamine, and the molecular signaling mechanisms for (2R,6R)-HNK remain unknown. Here, we examined the involvement of BDNF/TrkB/mechanistic target of rapamycin complex 1 (mTORC1) signaling in the antidepressant actions of (2R,6R)-HNK. Intramedial prefrontal cortex (intra-mPFC) infusion or systemic (2R,6R)-HNK administration induces rapid and long-lasting antidepressant effects in behavioral tests, identifying the mPFC as a key region for the actions of (2R,6R)-HNK. The antidepressant actions of (2R,6R)-HNK are blocked in mice with a knockin of the BDNF Val66Met allele (which blocks the processing and activity-dependent release of BDNF) or by intra-mPFC microinjection of an anti-BDNF neutralizing antibody. Blockade of L-type voltage-dependent Ca2+ channels (VDCCs), required for activity-dependent BDNF release, also blocks the actions of (2R,6R)-HNK. Intra-mPFC infusion of pharmacological inhibitors of TrkB or mTORC1 signaling, which are downstream of BDNF, also block the actions of (2R,6R)-HNK. Moreover, (2R,6R)-HNK increases synaptic function in the mPFC. These findings indicate that activity-dependent BDNF release and downstream TrkB and mTORC1 signaling, which increase synaptic function in the mPFC, are required for the rapid and long-lasting antidepressant effects of (2R,6R)-HNK, supporting the potential use of this metabolite for the treatment of MDD.}, } @article {pmid30559183, year = {2019}, author = {Sedaghatpour, F and Jacobsen, SB}, title = {Magnesium stable isotopes support the lunar magma ocean cumulate remelting model for mare basalts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {73-78}, doi = {10.1073/pnas.1811377115}, pmid = {30559183}, issn = {1091-6490}, abstract = {We report high-precision Mg isotopic analyses of different types of lunar samples including two pristine Mg-suite rocks (72415 and 76535), basalts, anorthosites, breccias, mineral separates, and lunar meteorites. The Mg isotopic composition of the dunite 72415 (δ25Mg = -0.140 ± 0.010‰, δ26Mg = -0.291 ± 0.018‰), the most Mg-rich and possibly the oldest lunar sample, may provide the best estimate of the Mg isotopic composition of the bulk silicate Moon (BSM). This δ26Mg value of the Moon is similar to those of the Earth and chondrites and reflects both the relative homogeneity of Mg isotopes in the solar system and the lack of Mg isotope fractionation by the Moon-forming giant impact. In contrast to the behavior of Mg isotopes in terrestrial basalts and mantle rocks, Mg isotopic data on lunar samples show isotopic variations among the basalts and pristine anorthositic rocks reflecting isotopic fractionation during the early lunar magma ocean (LMO) differentiation. Calculated evolutions of δ26Mg values during the LMO differentiation are consistent with the observed δ26Mg variations in lunar samples, implying that Mg isotope variations in lunar basalts are consistent with their origin by remelting of distinct LMO cumulates.}, } @article {pmid30559182, year = {2019}, author = {Sun, C and Li, T and Song, X and Huang, L and Zang, Q and Xu, J and Bi, N and Jiao, G and Hao, Y and Chen, Y and Zhang, R and Luo, Z and Li, X and Wang, L and Wang, Z and Song, Y and He, J and Abliz, Z}, title = {Spatially resolved metabolomics to discover tumor-associated metabolic alterations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {52-57}, doi = {10.1073/pnas.1808950116}, pmid = {30559182}, issn = {1091-6490}, abstract = {Characterization of tumor metabolism with spatial information contributes to our understanding of complex cancer metabolic reprogramming, facilitating the discovery of potential metabolic vulnerabilities that might be targeted for tumor therapy. However, given the metabolic variability and flexibility of tumors, it is still challenging to characterize global metabolic alterations in heterogeneous cancer. Here, we propose a spatially resolved metabolomics approach to discover tumor-associated metabolites and metabolic enzymes directly in their native state. A variety of metabolites localized in different metabolic pathways were mapped by airflow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) in tissues from 256 esophageal cancer patients. In combination with in situ metabolomics analysis, this method provided clues into tumor-associated metabolic pathways, including proline biosynthesis, glutamine metabolism, uridine metabolism, histidine metabolism, fatty acid biosynthesis, and polyamine biosynthesis. Six abnormally expressed metabolic enzymes that are closely associated with the altered metabolic pathways were further discovered in esophageal squamous cell carcinoma (ESCC). Notably, pyrroline-5-carboxylate reductase 2 (PYCR2) and uridine phosphorylase 1 (UPase1) were found to be altered in ESCC. The spatially resolved metabolomics reveal what occurs in cancer at the molecular level, from metabolites to enzymes, and thus provide insights into the understanding of cancer metabolic reprogramming.}, } @article {pmid30559181, year = {2018}, author = {Baker, SJ and Payne, DJ and Rappuoli, R and De Gregorio, E}, title = {Technologies to address antimicrobial resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12887-12895}, doi = {10.1073/pnas.1717160115}, pmid = {30559181}, issn = {1091-6490}, abstract = {Bacterial infections have been traditionally controlled by antibiotics and vaccines, and these approaches have greatly improved health and longevity. However, multiple stakeholders are declaring that the lack of new interventions is putting our ability to prevent and treat bacterial infections at risk. Vaccine and antibiotic approaches still have the potential to address this threat. Innovative vaccine technologies, such as reverse vaccinology, novel adjuvants, and rationally designed bacterial outer membrane vesicles, together with progress in polysaccharide conjugation and antigen design, have the potential to boost the development of vaccines targeting several classes of multidrug-resistant bacteria. Furthermore, new approaches to deliver small-molecule antibacterials into bacteria, such as hijacking active uptake pathways and potentiator approaches, along with a focus on alternative modalities, such as targeting host factors, blocking bacterial virulence factors, monoclonal antibodies, and microbiome interventions, all have potential. Both vaccines and antibacterial approaches are needed to tackle the global challenge of antimicrobial resistance (AMR), and both areas have the underpinning science to address this need. However, a concerted research agenda and rethinking of the value society puts on interventions that save lives, by preventing or treating life-threatening bacterial infections, are needed to bring these ideas to fruition.}, } @article {pmid30559180, year = {2019}, author = {McClure Carroll, EE and Wang, X and Shaw, DK and O'Neal, AJ and Oliva Chávez, AS and Brown, LJ and Boradia, VM and Hammond, HL and Pedra, JHF}, title = {p47 licenses activation of the immune deficiency pathway in the tick Ixodes scapularis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {205-210}, doi = {10.1073/pnas.1808905116}, pmid = {30559180}, issn = {1091-6490}, support = {F31 AI138440/AI/NIAID NIH HHS/United States ; P01 AI138949/AI/NIAID NIH HHS/United States ; R01 AI049424/AI/NIAID NIH HHS/United States ; R01 AI116523/AI/NIAID NIH HHS/United States ; }, abstract = {The E3 ubiquitin ligase X-linked inhibitor of apoptosis (XIAP) acts as a molecular rheostat for the immune deficiency (IMD) pathway of the tick Ixodes scapularis How XIAP activates the IMD pathway in response to microbial infection remains ill defined. Here, we identified the XIAP enzymatic substrate p47 as a positive regulator of the I. scapularis IMD network. XIAP polyubiquitylates p47 in a lysine 63-dependent manner and interacts with the p47 ubiquitin-like (UBX) module. p47 also binds to Kenny (IKKγ/NEMO), the regulatory subunit of the inhibitor of nuclear factor (NF)- κB kinase complex. Replacement of the amino acid lysine to arginine within the p47 linker region completely abrogated molecular interactions with Kenny. Furthermore, mitigation of p47 transcription levels through RNA interference in I. scapularis limited Kenny accumulation, reduced phosphorylation of IKKβ (IRD5), and impaired cleavage of the NF-κB molecule Relish. Accordingly, disruption of p47 expression increased microbial colonization by the Lyme disease spirochete Borrelia burgdorferi and the rickettsial agent Anaplasma phagocytophilum Collectively, we highlight the importance of ticks for the elucidation of paradigms in arthropod immunology. Manipulating immune signaling cascades within I. scapularis may lead to innovative approaches to reducing the burden of tick-borne diseases.}, } @article {pmid30559179, year = {2019}, author = {Guterstam, A and Kean, HH and Webb, TW and Kean, FS and Graziano, MSA}, title = {Implicit model of other people's visual attention as an invisible, force-carrying beam projecting from the eyes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {328-333}, doi = {10.1073/pnas.1816581115}, pmid = {30559179}, issn = {1091-6490}, abstract = {As a part of social cognition, people automatically construct rich models of other people's vision. Here we show that when people judge the mechanical forces acting on an object, their judgments are biased by another person gazing at the object. The bias is consistent with an implicit perception that gaze adds a gentle force, pushing on the object. The bias was present even though the participants were not explicitly aware of it and claimed that they did not believe in an extramission view of vision (a common folk view of vision in which the eyes emit an invisible energy). A similar result was not obtained on control trials when participants saw a blindfolded face turned toward the object, or a face with open eyes turned away from the object. The findings suggest that people automatically and implicitly generate a model of other people's vision that uses the simplifying construct of beams coming out of the eyes. This implicit model of active gaze may be a hidden, yet fundamental, part of the rich process of social cognition, contributing to how we perceive visual agency. It may also help explain the extraordinary cultural persistence of the extramission myth of vision.}, } @article {pmid30559178, year = {2018}, author = {}, title = {Correction for Mann, Inner Workings: Hunting for microbial life throughout the solar system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12464}, doi = {10.1073/pnas.1820385116}, pmid = {30559178}, issn = {1091-6490}, } @article {pmid30559177, year = {2019}, author = {Marzo, A and Drinkwater, BW}, title = {Holographic acoustic tweezers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {84-89}, doi = {10.1073/pnas.1813047115}, pmid = {30559177}, issn = {1091-6490}, abstract = {Acoustic tweezers use sound radiation forces to manipulate matter without contact. They provide unique characteristics compared with the more established optical tweezers, such as higher trapping forces per unit input power and the ability to manipulate objects from the micrometer to the centimeter scale. They also enable the trapping of a wide range of sample materials in various media. A dramatic advancement in optical tweezers was the development of holographic optical tweezers (HOT) which enabled the independent manipulation of multiple particles leading to applications such as the assembly of 3D microstructures and the probing of soft matter. Now, 20 years after the development of HOT, we present the realization of holographic acoustic tweezers (HAT). We experimentally demonstrate a 40-kHz airborne HAT system implemented using two 256-emitter phased arrays and manipulate individually up to 25 millimetric particles simultaneously. We show that the maximum trapping forces are achieved once the emitting array satisfies Nyquist sampling and an emission phase discretization below π/8 radians. When considered on the scale of a wavelength, HAT provides similar manipulation capabilities as HOT while retaining its unique characteristics. The examples shown here suggest the future use of HAT for novel forms of displays in which the objects are made of physical levitating voxels, assembly processes in the micrometer and millimetric scale, as well as positioning and orientation of multiple objects which could lead to biomedical applications.}, } @article {pmid30559176, year = {2018}, author = {Relman, DA and Lipsitch, M}, title = {Microbiome as a tool and a target in the effort to address antimicrobial resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12902-12910}, doi = {10.1073/pnas.1717163115}, pmid = {30559176}, issn = {1091-6490}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; R01 GM099534/GM/NIGMS NIH HHS/United States ; }, abstract = {Reciprocal, intimate relationships between the human microbiome and the host immune system are shaped by past microbial encounters and prepare the host for future ones. Antibiotics and other antimicrobials leave their mark on both the microbiome and host immunity. Antimicrobials alter the structure of the microbiota, expand the host-specific pool of antimicrobial-resistance genes and organisms, degrade the protective effects of the microbiota against invasion by pathogens, and may impair vaccine efficacy. Through these effects on the microbiome they may affect immune responses. Vaccines that exert protective or therapeutic effects against pathogens may reduce the use of antimicrobials, the development and spread of antimicrobial resistance, and the harmful impacts of these drugs on the microbiome. Other strategies involving manipulation of the microbiome to deplete antibiotic-resistant organisms or to enhance immune responses to vaccines may prove valuable in addressing antimicrobial resistance as well. This article describes the intersections of immunity, microbiome and antimicrobial exposure, and the use of vaccines and other alternative strategies for the control and management of antimicrobial resistance.}, } @article {pmid30558682, year = {2018}, author = {Sirová, D and Bárta, J and Šimek, K and Posch, T and Pech, J and Stone, J and Borovec, J and Adamec, L and Vrba, J}, title = {Hunters or farmers? Microbiome characteristics help elucidate the diet composition in an aquatic carnivorous plant.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {225}, doi = {10.1186/s40168-018-0600-7}, pmid = {30558682}, issn = {2049-2618}, support = {P504-17-10493S//Grantová Agentura České Republiky/ ; P504/11/0783//Grantová Agentura České Republiky/ ; RVO 67985939//Grantová Agentura České Republiky/ ; }, abstract = {BACKGROUND: Utricularia are rootless aquatic carnivorous plants which have recently attracted the attention of researchers due to the peculiarities of their miniaturized genomes. Here, we focus on a novel aspect of Utricularia ecophysiology-the interactions with and within the complex communities of microorganisms colonizing their traps and external surfaces.

RESULTS: Bacteria, fungi, algae, and protozoa inhabit the miniature ecosystem of the Utricularia trap lumen and are involved in the regeneration of nutrients from complex organic matter. By combining molecular methods, microscopy, and other approaches to assess the trap-associated microbial community structure, diversity, function, as well as the nutrient turn-over potential of bacterivory, we gained insight into the nutrient acquisition strategies of the Utricularia hosts.

CONCLUSIONS: We conclude that Utricularia traps can, in terms of their ecophysiological function, be compared to microbial cultivators or farms, which center around complex microbial consortia acting synergistically to convert complex organic matter, often of algal origin, into a source of utilizable nutrients for the plants.}, } @article {pmid30558673, year = {2018}, author = {Bell, GP and Kvajo, M}, title = {Tackling waste in publishing through portable peer review.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {146}, doi = {10.1186/s12915-018-0619-z}, pmid = {30558673}, issn = {1741-7007}, } @article {pmid30558669, year = {2018}, author = {Deshpande, NP and Riordan, SM and Castaño-Rodríguez, N and Wilkins, MR and Kaakoush, NO}, title = {Signatures within the esophageal microbiome are associated with host genetics, age, and disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {227}, doi = {10.1186/s40168-018-0611-4}, pmid = {30558669}, issn = {2049-2618}, support = {15/CDF/1-11//Cancer Institute NSW/ ; APP1111461//National Health and Medical Research Council/ ; }, abstract = {BACKGROUND: The esophageal microbiome has been proposed to be involved in a range of diseases including the esophageal adenocarcinoma cascade; however, little is currently known about its function and relationship to the host. Here, the esophageal microbiomes of 106 prospectively recruited patients were assessed using 16S rRNA and 18S rRNA amplicon sequencing as well as shotgun sequencing, and associations with age, gender, proton pump inhibitor use, host genetics, and disease were tested.

RESULTS: The esophageal microbiome was found to cluster into functionally distinct community types (esotypes) defined by the relative abundances of Streptococcus and Prevotella. While age was found to be a significant factor driving microbiome composition, bacterial signatures and functions such as enrichment with Gram-negative oral-associated bacteria and microbial lactic acid production were associated with the early stages of the esophageal adenocarcinoma cascade. Non-bacterial microbes such as archaea, Candida spp., and bacteriophages were also identified in low abundance in the esophageal microbiome. Specific host SNPs in NOTCH2, STEAP2-AS1, and NREP were associated with the composition of the esophageal microbiome in our cohort.

CONCLUSIONS: This study provides the most comprehensive assessment of the esophageal microbiome to date and identifies novel signatures and host markers that can be investigated further in the context of esophageal adenocarcinoma development.}, } @article {pmid30558668, year = {2018}, author = {Davis, NM and Proctor, DM and Holmes, SP and Relman, DA and Callahan, BJ}, title = {Simple statistical identification and removal of contaminant sequences in marker-gene and metagenomics data.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {226}, doi = {10.1186/s40168-018-0605-2}, pmid = {30558668}, issn = {2049-2618}, support = {R01 AI112401/AI/NIAID NIH HHS/United States ; R01 DE023113/DE/NIDCR NIH HHS/United States ; R01 DE023113//National Institute of Dental and Craniofacial Research/ ; R01 AI112401//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: The accuracy of microbial community surveys based on marker-gene and metagenomic sequencing (MGS) suffers from the presence of contaminants-DNA sequences not truly present in the sample. Contaminants come from various sources, including reagents. Appropriate laboratory practices can reduce contamination, but do not eliminate it. Here we introduce decontam (https://github.com/benjjneb/decontam), an open-source R package that implements a statistical classification procedure that identifies contaminants in MGS data based on two widely reproduced patterns: contaminants appear at higher frequencies in low-concentration samples and are often found in negative controls.

RESULTS: Decontam classified amplicon sequence variants (ASVs) in a human oral dataset consistently with prior microscopic observations of the microbial taxa inhabiting that environment and previous reports of contaminant taxa. In metagenomics and marker-gene measurements of a dilution series, decontam substantially reduced technical variation arising from different sequencing protocols. The application of decontam to two recently published datasets corroborated and extended their conclusions that little evidence existed for an indigenous placenta microbiome and that some low-frequency taxa seemingly associated with preterm birth were contaminants.

CONCLUSIONS: Decontam improves the quality of metagenomic and marker-gene sequencing by identifying and removing contaminant DNA sequences. Decontam integrates easily with existing MGS workflows and allows researchers to generate more accurate profiles of microbial communities at little to no additional cost.}, } @article {pmid30558667, year = {2018}, author = {Tesfay, K and Yohannes, M and Bayisa, S}, title = {Trend analysis of malaria prevalence in Raya Azebo district, Northern Ethiopia: a retrospective study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {900}, doi = {10.1186/s13104-018-4003-4}, pmid = {30558667}, issn = {1756-0500}, abstract = {OBJECTIVE: Malaria remains still the leading cause of outpatient visits and death in Ethiopia. However, little is known about its trend in the study area. Hence, this study was aimed to assess 6-year (2011-2016) trend of malaria prevalence. A retrospective cross-sectional study design was conducted to assess 6-year trends of malaria prevalence in Raya Azebo district, North Ethiopia. Malaria case recorded from 2011 to 2016 was extracted using similar format.

RESULT: A total of 29,930 malaria cases were reported from 2011 to 2016. Of these, 23,018 were confirmed cases while, 6912 were reported as clinical cases. Plasmodium falciparum (56.9%) was the most dominated species. Malaria was reported in all age group and both sexes with highest in male and > 15 age categories. The highest peak malaria distribution was occurred in spring season. The overall trends of malaria case were increased in the past 6 years (2011-2016) with exception slightly decreased from 2012 to 2013. Therefore, Strong effort is needed to improve malaria prevention and controlling method in study area.}, } @article {pmid30558657, year = {2018}, author = {Cervantes-Echeverría, M and Equihua-Medina, E and Cornejo-Granados, F and Hernández-Reyna, A and Sánchez, F and López-Contreras, BE and Canizales-Quinteros, S and Ochoa-Leyva, A}, title = {Whole-genome of Mexican-crAssphage isolated from the human gut microbiome.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {902}, doi = {10.1186/s13104-018-4010-5}, pmid = {30558657}, issn = {1756-0500}, support = {SALUD-2014-C01-234188//Consejo Nacional de Ciencia y Tecnología/ ; }, abstract = {OBJECTIVES: crAssphage is a newly found phage described as the most abundant virus in the human gut microbiome. The majority of the crAssphage proteins are unknown in sequences databases, and its pathogenicity and epidemiology in humans are yet unclear. Hence, being one of the most abundant phages in the human gut microbiome more investigation at the genomic level is necessary to improve our understanding, especially in the Latin American population.

DATA DESCRIPTION: In this article, we provide the whole genome of a crAssphage isolated from the human gut microbiome of the Mexican population, which was named Mexican-crAssphage. The genome consists of 96,283 bp, G+C content of 29.24% and 87 coding sequences. Notably, we did not find any transfer RNA genes in the genome sequence. We also sequenced viral-like enriched particles from 28 fecal samples, and we detected the presence of the Mexican-crAssphage genome in 8 samples (28.5%). To our knowledge, our data is the first whole genome report of the crAssphage isolated from the Latin American Population and provides valuable information for the experimental characterization of the most abundant human gut bacteriophage. The whole genome shotgun project of the Mexican-crAssphage is available at DDBJ/ENA/GenBank under the GenBank MK069403.}, } @article {pmid30558656, year = {2018}, author = {Forson, AO and Tsidi, WB and Nana-Adjei, D and Quarchie, MN and Obeng-Nkrumah, N}, title = {Escherichia coli bacteriuria in pregnant women in Ghana: antibiotic resistance patterns and virulence factors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {901}, doi = {10.1186/s13104-018-3989-y}, pmid = {30558656}, issn = {1756-0500}, abstract = {OBJECTIVES: The relevance of Escherichia coli associated bacteriuria infection in pregnant women is poorly understood, despite these strains sharing a similar virulence profile with other pathogenic E. coli causing severe obstetric and neonatal infections. We characterized and determined the antimicrobial susceptibility, resistance genes and virulence profiles of 82 E. coli isolates associated with asymptomatic bacteriuria in some pregnant in Ghana from February to August 2016 using Kirby-Bauer disc diffusion and polymerase chain reaction.

RESULTS: High levels of antimicrobial resistance were observed to ampicillin (79.3%), tetracycline (70.7%) and cotrimoxazole (59.8%), except for cefuroxime (32.9%). Resistance genes analyses revealed 58.5% were positive for BlaTEM and 7.3% for aph(3)-Ia(aphA2). Virulence factors (VFs) was more widespread in pregnant women in the 2nd and 3rd trimesters than 1st trimester. VFs relating to adhesion (papC and iha), Protectins (traT), aerobactin acquisition (iutA) and iron acquisition systems (fyuA and irp2) were more prevalent in the resistant E. coli isolates. This study provides evidence for a link in bacteriuria and transmission of extra-intestinal E. coli in pregnant women to cause multi-resistant obstetric or neonatal infections. Considering the involvement of extra-intestinal E. coli in infections, results are helpful to develop strategies to prevent maternal and/ neonatal infections.}, } @article {pmid30558642, year = {2018}, author = {Bolton, P and McCulloch, TJ}, title = {The evidence supporting WHO recommendations on the promotion of hand hygiene: a critique.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {899}, doi = {10.1186/s13104-018-4012-3}, pmid = {30558642}, issn = {1756-0500}, abstract = {OBJECTIVE: To examine the quality of the evidence relied upon by the World Health Organisation (WHO) in promoting hand hygiene with campaigns such as "Save Lives: Clean Your Hands".

RESULTS: The quality of evidence in the studies quoted by the WHO evidence document is highly variable and the methods used limited. In some of the quoted studies, hand hygiene was the primary outcome, rather than the clinically significant outcome of hospital acquired infection (HAI). When HAI was the primary outcome, it was often poorly defined and reported with scant detail. There was wide variation in the hand hygiene compliance achieved in the intervention studies. The majority of studies where the intervention was a campaign to promote hand hygiene used historical control data with variable attempts to account for the fact that HAI rates may have been declining prior to the hand hygiene intervention. The results from trials with a contemporaneous control were conflicting.}, } @article {pmid30558598, year = {2018}, author = {Delelegn, YT and Purahong, W and Sandén, H and Yitaferu, B and Godbold, DL and Wubet, T}, title = {Transition of Ethiopian highland forests to agriculture-dominated landscapes shifts the soil microbial community composition.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {58}, doi = {10.1186/s12898-018-0214-8}, pmid = {30558598}, issn = {1472-6785}, support = {BMLFUW - UW.1.3.2/0122 - V/4/2013//Bundesministerium für Land- und Forstwirtschaft, Umwelt und Wasserwirtschaft (AT)/ ; }, abstract = {BACKGROUND: Land use changes and related land management practices significantly alter soil physicochemical properties; however, their effects on the soil microbial community structure are still unclear. In this study, we used automated ribosomal intergenic spacer analysis to determine the fungal and bacterial community composition in soils from different land use areas in the Ethiopian highlands. Soil samples were collected from five areas with different land uses, natural forest, eucalyptus plantation, exclosure, grassland and cropland, which had all historically been natural forest.

RESULTS: Our results showed a significant shift in the soil bacterial and fungal community composition in response to land use change. We also identified soil physicochemical factors corresponding to the changes in bacterial and fungal communities. Although most soil attributes, including soil organic carbon, total soil nitrogen, labile P, soil pH and soil aggregate stability, were related to the change in bacterial community composition, the total soil nitrogen and soil organic carbon had the strongest relationships. The change in fungal community composition was correlated with soil nutrients, organic carbon, soil nitrogen and particularly the labile P concentration.

CONCLUSIONS: The fungal community composition was likely affected by the alteration of vegetation cover in response to land use change, whereas the bacterial communities were mainly sensitive to changes in soil attributes. The study highlights the higher sensitivity of fungal communities than bacterial communities to land use changes.}, } @article {pmid30558589, year = {2018}, author = {Neumann, G and Wall, R and Rangel, I and Marques, TM and Repsilber, D}, title = {Qualitative modelling of the interplay of inflammatory status and butyrate in the human gut: a hypotheses about robust bi-stability.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {144}, doi = {10.1186/s12918-018-0667-6}, pmid = {30558589}, issn = {1752-0509}, support = {20110225//Swedish Knowledge Foundation (KK Stiftelse)/ ; }, abstract = {BACKGROUND: Gut microbiota interacts with the human gut in multiple ways. Microbiota composition is altered in inflamed gut conditions. Likewise, certain microbial fermentation products as well as the lipopolysaccharides of the outer membrane are examples of microbial products with opposing influences on gut epithelium inflammation status. This system of intricate interactions is known to play a core role in human gut inflammatory diseases. Here, we present and analyse a simplified model of bidirectional interaction between the microbiota and the host: in focus is butyrate as an example for a bacterial fermentation product with anti-inflammatory properties.

RESULTS: We build a dynamical model based on an existing model of inflammatory regulation in gut epithelial cells. Our model introduces both butyrate as a bacterial product which counteracts inflammation, as well as bacterial LPS as a pro-inflammatory bacterial product. Moreover, we propose an extension of this model that also includes a feedback interaction towards bacterial composition. The analysis of these dynamical models shows robust bi-stability driven by butyrate concentrations in the gut. The extended model hints towards a further possible enforcement of the observed bi-stability via alteration of gut bacterial composition. A theoretical perspective on the stability of the described switch-like character is discussed.

CONCLUSIONS: Interpreting the results of this qualitative model allows formulating hypotheses about the switch-like character of inflammatory regulation in the gut epithelium, involving bacterial products as constitutive parts of the system. We also speculate about possible explanations for observed bimodal distributions in bacterial compositions in the human gut. The switch-like behaviour of the system proved to be mostly independent of parameter choices. Further implications of the qualitative character of our modeling approach for the robustness of the proposed hypotheses are discussed, as well as the pronounced role of butyrate compared to other inflammatory regulators, especially LPS, NF- κB and cytokines.}, } @article {pmid30558585, year = {2018}, author = {Guzmán, GI and Olson, CA and Hefner, Y and Phaneuf, PV and Catoiu, E and Crepaldi, LB and Micas, LG and Palsson, BO and Feist, AM}, title = {Reframing gene essentiality in terms of adaptive flexibility.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {143}, doi = {10.1186/s12918-018-0653-z}, pmid = {30558585}, issn = {1752-0509}, support = {U01 AI124316/AI/NIAID NIH HHS/United States ; NNF10CC1016517//Novo Nordisk (DK)/ ; 1-U01-AI124316//National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: Essentiality assays are important tools commonly utilized for the discovery of gene functions. Growth/no growth screens of single gene knockout strain collections are also often utilized to test the predictive power of genome-scale models. False positive predictions occur when computational analysis predicts a gene to be non-essential, however experimental screens deem the gene to be essential. One explanation for this inconsistency is that the model contains the wrong information, possibly an incorrectly annotated alternative pathway or isozyme reaction. Inconsistencies could also be attributed to experimental limitations, such as growth tests with arbitrary time cut-offs. The focus of this study was to resolve such inconsistencies to better understand isozyme activities and gene essentiality.

RESULTS: In this study, we explored the definition of conditional essentiality from a phenotypic and genomic perspective. Gene-deletion strains associated with false positive predictions of gene essentiality on defined minimal medium for Escherichia coli were targeted for extended growth tests followed by population sequencing and transcriptome analysis. Of the twenty false positive strains available and confirmed from the Keio single gene knock-out collection, 11 strains were shown to grow with longer incubation periods making these actual true positives. These strains grew reproducibly with a diverse range of growth phenotypes. The lag phase observed for these strains ranged from less than one day to more than 7 days. It was found that 9 out of 11 of the false positive strains that grew acquired mutations in at least one replicate experiment and the types of mutations ranged from SNPs and small indels associated with regulatory or metabolic elements to large regions of genome duplication. Comparison of the detected adaptive mutations, modeling predictions of alternate pathways and isozymes, and transcriptome analysis of KO strains suggested agreement for the observed growth phenotype for 6 out of the 9 cases where mutations were observed.

CONCLUSIONS: Longer-term growth experiments followed by whole genome sequencing and transcriptome analysis can provide a better understanding of conditional gene essentiality and mechanisms of adaptation to such perturbations. Compensatory mutations are largely reproducible mechanisms and are in agreement with genome-scale modeling predictions to loss of function gene deletion events.}, } @article {pmid30558550, year = {2018}, author = {Watson-Haigh, NS and Suchecki, R and Kalashyan, E and Garcia, M and Baumann, U}, title = {DAWN: a resource for yielding insights into the diversity among wheat genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {941}, doi = {10.1186/s12864-018-5228-2}, pmid = {30558550}, issn = {1471-2164}, abstract = {BACKGROUND: Democratising the growing body of whole genome sequencing data available for Triticum aestivum (bread wheat) has been impeded by the lack of a genome reference and the large computational requirements for analysing these data sets.

RESULTS: DAWN (Diversity Among Wheat geNomes) integrates data from the T. aestivum Chinese Spring (CS) IWGSC RefSeq v1.0 genome with public WGS and exome data from 17 and 62 accessions respectively, enabling researchers and breeders alike to investigate genotypic differences between wheat accessions at the level of whole chromosomes down to individual genes.

CONCLUSIONS: Using DAWN we show that it is possible to visualise small and large chromosomal deletions, identify haplotypes at a glance and spot the consequences of selective breeding. DAWN allows us to detect the break points of alien introgression segments brought into an accession when transferring desired genes. Furthermore, we can find possible explanations for reduced recombination in parts of a chromosome, we can predict regions with linkage drag, and also look at diversity in centromeric regions.}, } @article {pmid30558544, year = {2018}, author = {Abbas, HMK and Xiang, J and Ahmad, Z and Wang, L and Dong, W}, title = {Enhanced Nicotiana benthamiana immune responses caused by heterologous plant genes from Pinellia ternata.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {357}, doi = {10.1186/s12870-018-1598-5}, pmid = {30558544}, issn = {1471-2229}, support = {2016ZX08003-001//The National Major Project for Transgenic Organism Breeding/ ; 2016ABA093//The Hubei Provincial Technology Innovation Program/ ; }, mesh = {Antioxidants/metabolism ; Gene Expression Regulation, Plant ; Glucans/genetics/metabolism ; Host-Pathogen Interactions/genetics/immunology ; Phytophthora/pathogenicity ; Pinellia/*genetics ; Plant Diseases/immunology/microbiology ; Plant Immunity/*genetics ; Plant Leaves/genetics/metabolism ; Plants, Genetically Modified ; Reactive Oxygen Species/metabolism ; Tobacco/*genetics/*immunology ; }, abstract = {BACKGROUND: Pinellia ternata is a Chinese traditional medicinal herb, used to cure diseases including insomnia, eclampsia and cervical carcinoma, for hundreds of years. Non-self-recognition in multicellular organisms can initiate the innate immunity to avoid the invasion of pathogens. A design for pathogen independent, heterosis based, fresh resistance can be generated in F1 hybrid was proposed.

RESULTS: By library functional screening, we found that P. ternata genes, named as ptHR375 and ptHR941, were identified with the potential to trigger a hypersensitive response in Nicotiana benthamiana. Significant induction of ROS and Callose deposition in N. benthamiana leaves along with activation of pathogenesis-related genes viz.; PR-1a, PR-5, PDF1.2, NPR1, PAL, RBOHB and ERF1 and antioxidant enzymes was observed. After transformation into N. benthamiana, expression of pathogenesis related genes was significantly up-regulated to generate high level of resistance against Phytophthora capsici without affecting the normal seed germination and morphological characters of the transformed N. benthamiana. UPLC-QTOF-MS analysis of ptHR375 transformed N. benthamiana revealed the induction of Oxytetracycline, Cuelure, Allantoin, Diethylstilbestrol and 1,2-Benzisothiazol-3(2H)-one as bioactive compounds. Here we also proved that F1 hybrids, produced by crossing of the ptHR375 and ptHR941 transformed and non-transformed N. benthamiana, show significant high levels of PR-gene expressions and pathogen resistance.

CONCLUSIONS: Heterologous plant genes can activate disease resistance in another plant species and furthermore, by generating F1 hybrids, fresh pathogen independent plant immunity can be obtained. It is also concluded that ptHR375 and ptHR941 play their role in SA and JA/ET defense pathways to activate the resistance against invading pathogens.}, } @article {pmid30558543, year = {2018}, author = {Minas, IS and Tanou, G and Krokida, A and Karagiannis, E and Belghazi, M and Vasilakakis, M and Papadopoulou, KK and Molassiotis, A}, title = {Ozone-induced inhibition of kiwifruit ripening is amplified by 1-methylcyclopropene and reversed by exogenous ethylene.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {358}, doi = {10.1186/s12870-018-1584-y}, pmid = {30558543}, issn = {1471-2229}, support = {Greek national funds through the Operational Program 'Education and Lifelong Learning' of the National Strategic Reference Framework (NSRF) - Research Funding Program: Thales.//85553/ ; }, mesh = {Actinidia/drug effects/*physiology ; Cyclopropanes/*pharmacology ; Ethylenes/metabolism/*pharmacology ; Food Storage ; Fruit/drug effects/*physiology ; Gene Expression Regulation, Plant/drug effects ; Ozone/metabolism/*pharmacology ; Plant Proteins/metabolism ; Signal Transduction/drug effects ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Understanding the mechanisms involved in climacteric fruit ripening is key to improve fruit harvest quality and postharvest performance. Kiwifruit (Actinidia deliciosa cv. 'Hayward') ripening involves a series of metabolic changes regulated by ethylene. Although 1-methylcyclopropene (1-MCP, inhibitor of ethylene action) or ozone (O3) exposure suppresses ethylene-related kiwifruit ripening, how these molecules interact during ripening is unknown.

RESULTS: Harvested 'Hayward' kiwifruits were treated with 1-MCP and exposed to ethylene-free cold storage (0 °C, RH 95%) with ambient atmosphere (control) or atmosphere enriched with O3 (0.3 μL L- 1) for up to 6 months. Their subsequent ripening performance at 20 °C (90% RH) was characterized. Treatment with either 1-MCP or O3 inhibited endogenous ethylene biosynthesis and delayed fruit ripening at 20 °C. 1-MCP and O3 in combination severely inhibited kiwifruit ripening, significantly extending fruit storage potential. To characterize ethylene sensitivity of kiwifruit following 1-MCP and O3 treatments, fruit were exposed to exogenous ethylene (100 μL L- 1, 24 h) upon transfer to 20 °C following 4 and 6 months of cold storage. Exogenous ethylene treatment restored ethylene biosynthesis in fruit previously exposed in an O3-enriched atmosphere. Comparative proteomics analysis showed separate kiwifruit ripening responses, unraveled common 1-MCP- and O3-dependent metabolic pathways and identified specific proteins associated with these different ripening behaviors. Protein components that were differentially expressed following exogenous ethylene exposure after 1-MCP or O3 treatment were identified and their protein-protein interaction networks were determined. The expression of several kiwifruit ripening related genes, such as 1-aminocyclopropane-1-carboxylic acid oxidase (ACO1), ethylene receptor (ETR1), lipoxygenase (LOX1), geranylgeranyl diphosphate synthase (GGP1), and expansin (EXP2), was strongly affected by O3, 1-MCP, their combination, and exogenously applied ethylene.

CONCLUSIONS: Our findings suggest that the combination of 1-MCP and O3 functions as a robust repressive modulator of kiwifruit ripening and provide new insight into the metabolic events underlying ethylene-induced and ethylene-independent ripening outcomes.}, } @article {pmid30558541, year = {2018}, author = {Mattioli, R and Biancucci, M and El Shall, A and Mosca, L and Costantino, P and Funck, D and Trovato, M}, title = {Proline synthesis in developing microspores is required for pollen development and fertility.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {356}, doi = {10.1186/s12870-018-1571-3}, pmid = {30558541}, issn = {1471-2229}, support = {n.a.//Sapienza Università di Roma/ ; n.a.//University of Konstanz/ ; Progetti di Ricerca di Interesse Nazionale//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Arabidopsis/genetics/*physiology ; Arabidopsis Proteins/*genetics/metabolism ; Fertility ; Flowers/genetics/metabolism ; Gene Expression Regulation, Plant ; Glutamate-5-Semialdehyde Dehydrogenase/*genetics/metabolism ; Multienzyme Complexes/*genetics/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/*genetics/metabolism ; Plants, Genetically Modified ; Pollen/*genetics/*growth & development ; Proline/*biosynthesis ; Promoter Regions, Genetic ; Spores/genetics ; }, abstract = {BACKGROUND: In many plants, the amino acid proline is strongly accumulated in pollen and disruption of proline synthesis caused abortion of microspore development in Arabidopsis. So far, it was unclear whether local biosynthesis or transport of proline determines the success of fertile pollen development.

RESULTS: We analyzed the expression pattern of the proline biosynthetic genes PYRROLINE-5-CARBOXYLATE SYNTHETASE 1 & 2 (P5CS1 & 2) in Arabidopsis anthers and both isoforms were strongly expressed in developing microspores and pollen grains but only inconsistently in surrounding sporophytic tissues. We introduced in a p5cs1/p5cs1 p5cs2/P5CS2 mutant background an additional copy of P5CS2 under the control of the Cauliflower Mosaic Virus (CaMV) 35S promoter, the tapetum-specific LIPID TRANSFER PROTEIN 12 (Ltp12) promoter or the pollen-specific At5g17340 promoter to determine in which site proline biosynthesis can restore the fertility of proline-deficient microspores. The specificity of these promoters was confirmed by β-glucuronidase (GUS) analysis, and by direct proline measurement in pollen grains and stage-9/10 anthers. Expression of P5CS2 under control of the At5g17340 promoter fully rescued proline content and normal morphology and fertility of mutant pollen. In contrast, expression of P5CS2 driven by either the Ltp12 or CaMV35S promoter caused only partial restoration of pollen development with little effect on pollen fertility.

CONCLUSIONS: Overall, our results indicate that proline transport is not able to fulfill the demand of the cells of the male germ line. Pollen development and fertility depend on local proline biosynthesis during late stages of microspore development and in mature pollen grains.}, } @article {pmid30558539, year = {2018}, author = {Hao, J and Kim, Y and Kim, TK and Kang, M}, title = {PASNet: pathway-associated sparse deep neural network for prognosis prediction from high-throughput data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {510}, doi = {10.1186/s12859-018-2500-z}, pmid = {30558539}, issn = {1471-2105}, mesh = {Area Under Curve ; Biomarkers, Tumor ; Glioblastoma/*genetics/*pathology/therapy ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Neural Networks (Computer) ; Predictive Value of Tests ; Prognosis ; *Software ; }, abstract = {BACKGROUND: Predicting prognosis in patients from large-scale genomic data is a fundamentally challenging problem in genomic medicine. However, the prognosis still remains poor in many diseases. The poor prognosis may be caused by high complexity of biological systems, where multiple biological components and their hierarchical relationships are involved. Moreover, it is challenging to develop robust computational solutions with high-dimension, low-sample size data.

RESULTS: In this study, we propose a Pathway-Associated Sparse Deep Neural Network (PASNet) that not only predicts patients' prognoses but also describes complex biological processes regarding biological pathways for prognosis. PASNet models a multilayered, hierarchical biological system of genes and pathways to predict clinical outcomes by leveraging deep learning. The sparse solution of PASNet provides the capability of model interpretability that most conventional fully-connected neural networks lack. We applied PASNet for long-term survival prediction in Glioblastoma multiforme (GBM), which is a primary brain cancer that shows poor prognostic performance. The predictive performance of PASNet was evaluated with multiple cross-validation experiments. PASNet showed a higher Area Under the Curve (AUC) and F1-score than previous long-term survival prediction classifiers, and the significance of PASNet's performance was assessed by Wilcoxon signed-rank test. Furthermore, the biological pathways, found in PASNet, were referred to as significant pathways in GBM in previous biology and medicine research.

CONCLUSIONS: PASNet can describe the different biological systems of clinical outcomes for prognostic prediction as well as predicting prognosis more accurately than the current state-of-the-art methods. PASNet is the first pathway-based deep neural network that represents hierarchical representations of genes and pathways and their nonlinear effects, to the best of our knowledge. Additionally, PASNet would be promising due to its flexible model representation and interpretability, embodying the strengths of deep learning. The open-source code of PASNet is available at https://github.com/DataX-JieHao/PASNet .}, } @article {pmid30558537, year = {2018}, author = {Yu, R and Ma, Y and Li, Y and Li, X and Liu, C and Du, X and Shi, G}, title = {Comparative transcriptome analysis revealed key factors for differential cadmium transport and retention in roots of two contrasting peanut cultivars.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {938}, doi = {10.1186/s12864-018-5304-7}, pmid = {30558537}, issn = {1471-2164}, support = {31671599 and 31370515//National Natural Science Foundation of China/ ; 1708085MC55//Natural Science Foundation of Anhui Province of China/ ; }, abstract = {BACKGROUND: Peanut is the world's fourth largest oilseed crop that exhibits wide cultivar variations in cadmium (Cd) accumulation. To establish the mechanisms of Cd distribution and accumulation in peanut plants, eight cDNA libraries from the roots of two contrasting cultivars, Fenghua 1 (low-Cd cultivar) and Silihong (high-Cd cultivar), were constructed and sequenced by RNA-sequencing. The expression patterns of 16 candidate DEGs were validated by RT-qPCR analysis.

RESULTS: A total of 75,634 genes including 71,349 known genes and 4484 novel genes were identified in eight cDNA libraries, among which 6798 genes were found to be Cd-responsive DEGs and/or DEGs between these two cultivars. Interestingly, 183 DEGs encoding ion transport related proteins and 260 DEGs encoding cell wall related proteins were identified. Among these DEGs, nine metal transporter genes (PDR1, ABCC4 and ABCC15, IRT1, ZIP1, ZIP11, YSL7, DTX43 and MTP4) and nine cell wall related genes (PEs, PGIPs, GTs, XYT12 CYP450s, LACs, 4CL2, C4H and CASP5) showed higher expression in Fenghua 1 than in Silihong.

CONCLUSIONS: Both the metal transporters and cell wall modification might be responsible for the difference in Cd accumulation and translocation between Fenghua 1 and Silihong. These findings would be useful for further functional analysis, and reveal the molecular mechanism responsible for genotype difference in Cd accumulation.}, } @article {pmid30558536, year = {2018}, author = {Jia, X and Han, Q and Lu, Z}, title = {Analyzing the similarity of samples and genes by MG-PCC algorithm, t-SNE-SS and t-SNE-SG maps.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {512}, doi = {10.1186/s12859-018-2495-5}, pmid = {30558536}, issn = {1471-2105}, support = {2016YFA0501600//Major Program of National Natural Science Foundation of China/ ; }, mesh = {*Algorithms ; Biomarkers, Tumor/*genetics ; Computational Biology/*methods ; *Gene Expression Regulation, Neoplastic ; Genetic Variation ; Humans ; Neoplasms/*genetics/pathology/therapy ; }, abstract = {BACKGROUND: For analyzing these gene expression data sets under different samples, clustering and visualizing samples and genes are important methods. However, it is difficult to integrate clustering and visualizing techniques when the similarities of samples and genes are defined by PCC(Person correlation coefficient) measure.

RESULTS: Here, for rare samples of gene expression data sets, we use MG-PCC (mini-groups that are defined by PCC) algorithm to divide them into mini-groups, and use t-SNE-SSP maps to display these mini-groups, where the idea of MG-PCC algorithm is that the nearest neighbors should be in the same mini-groups, t-SNE-SSP map is selected from a series of t-SNE(t-statistic Stochastic Neighbor Embedding) maps of standardized samples, and these t-SNE maps have different perplexity parameter. Moreover, for PCC clusters of mass genes, they are displayed by t-SNE-SGI map, where t-SNE-SGI map is selected from a series of t-SNE maps of standardized genes, and these t-SNE maps have different initialization dimensions. Here, t-SNE-SSP and t-SNE-SGI maps are selected by A-value, where A-value is modeled from areas of clustering projections, and t-SNE-SSP and t-SNE-SGI maps are such t-SNE map that has the smallest A-value.

CONCLUSIONS: From the analysis of cancer gene expression data sets, we demonstrate that MG-PCC algorithm is able to put tumor and normal samples into their respective mini-groups, and t-SNE-SSP(or t-SNE-SGI) maps are able to display the relationships between mini-groups(or PCC clusters) clearly. Furthermore, t-SNE-SS(m)(or t-SNE-SG(n)) maps are able to construct independent tree diagrams of the nearest sample(or gene) neighbors, where each tree diagram is corresponding to a mini-group of samples(or genes).}, } @article {pmid30558535, year = {2018}, author = {Huen, A and Bally, J and Smith, P}, title = {Identification and characterisation of microRNAs and their target genes in phosphate-starved Nicotiana benthamiana by small RNA deep sequencing and 5'RACE analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {940}, doi = {10.1186/s12864-018-5258-9}, pmid = {30558535}, issn = {1471-2164}, support = {GRS10248//Grains Research and Development Corporation/ ; }, abstract = {BACKGROUND: Phosphorus is an important macronutrient that is severely lacking in soils. In plants, specific microRNAs (miRNAs) essential for nutrient management and the regulation of stress responses are responsible for the control of many phosphate starvation responses. Further understanding of conserved and species-specific microRNA species has potential implications for the development of crops tolerant to soils with low phosphate.

RESULTS: This study identified and characterised phosphate starvation-responsive miRNAs in the native Australian tobacco Nicotiana benthamiana. Small RNA libraries were constructed and sequenced from phosphate-starved plant leaves, stems and roots. Twenty-four conserved miRNA families and 36 species-specific miRNAs were identified. The majority of highly phosphate starvation-responsive miRNAs were highly conserved, comprising of members from the miR399, miR827, and miR2111 families. In addition, two miRNA-star species were identified to be phosphate starvation-responsive. A total of seven miRNA targets were confirmed using RLM-5'RACE to be cleaved by five miRNA families, including two confirmed cleavage targets for Nbe-miR399 species, one for Nbe-miR2111, and two for Nbe-miR398. A number of N. benthamiana-specific features for conserved miRNAs were identified, including species-specific miRNA targets predicted or confirmed for miR399, miR827, and miR398.

CONCLUSIONS: Our results give an insight into the phosphate starvation-responsive miRNAs of Nicotiana benthamiana, and indicate that the phosphate starvation response pathways in N. benthamiana contain both highly conserved and species-specific components.}, } @article {pmid30558534, year = {2018}, author = {Salleh, SM and Mazzoni, G and Løvendahl, P and Kadarmideen, HN}, title = {Gene co-expression networks from RNA sequencing of dairy cattle identifies genes and pathways affecting feed efficiency.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {513}, doi = {10.1186/s12859-018-2553-z}, pmid = {30558534}, issn = {1471-2105}, mesh = {*Animal Feed ; Animals ; Cattle ; Computational Biology ; *Diet ; Female ; Gene Expression Regulation ; *Gene Regulatory Networks ; *Genome ; High-Throughput Nucleotide Sequencing ; Liver/*metabolism ; Metabolic Networks and Pathways ; Phenotype ; Sequence Analysis, RNA/*methods ; *Transcriptome ; }, abstract = {BACKGROUND: Selection for feed efficiency is crucial for overall profitability and sustainability in dairy cattle production. Key regulator genes and genetic markers derived from co-expression networks underlying feed efficiency could be included in the genomic selection of the best cows. The present study identified co-expression networks associated with high and low feed efficiency and their regulator genes in Danish Holstein and Jersey cows. RNA-sequencing data from Holstein and Jersey cows with high and low residual feed intake (RFI) and treated with two diets (low and high concentrate) were used. Approximately 26 million and 25 million pair reads were mapped to bovine reference genome for Jersey and Holstein breed, respectively. Subsequently, the gene count expressions data were analysed using a Weighted Gene Co-expression Network Analysis (WGCNA) approach. Functional enrichment analysis from Ingenuity® Pathway Analysis (IPA®), ClueGO application and STRING of these modules was performed to identify relevant biological pathways and regulatory genes.

RESULTS: WGCNA identified two groups of co-expressed genes (modules) significantly associated with RFI and one module significantly associated with diet. In Holstein cows, the salmon module with module trait relationship (MTR) = 0.7 and the top upstream regulators ATP7B were involved in cholesterol biosynthesis, steroid biosynthesis, lipid biosynthesis and fatty acid metabolism. The magenta module has been significantly associated (MTR = 0.51) with the treatment diet involved in the triglyceride homeostasis. In Jersey cows, the lightsteelblue1 (MTR = - 0.57) module controlled by IFNG and IL10RA was involved in the positive regulation of interferon-gamma production, lymphocyte differentiation, natural killer cell-mediated cytotoxicity and primary immunodeficiency.

CONCLUSION: The present study provides new information on the biological functions in liver that are potentially involved in controlling feed efficiency. The hub genes and upstream regulators (ATP7b, IFNG and IL10RA) involved in these functions are potential candidate genes for the development of new biomarkers. However, the hub genes, upstream regulators and pathways involved in the co-expressed networks were different in both breeds. Hence, additional studies are required to investigate and confirm these findings prior to their use as candidate genes.}, } @article {pmid30558533, year = {2018}, author = {Singchat, W and O'Connor, RE and Tawichasri, P and Suntronpong, A and Sillapaprayoon, S and Suntrarachun, S and Muangmai, N and Baicharoen, S and Peyachoknagul, S and Chanhome, L and Griffin, D and Srikulnath, K}, title = {Chromosome map of the Siamese cobra: did partial synteny of sex chromosomes in the amniote represent "a hypothetical ancestral super-sex chromosome" or random distribution?.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {939}, doi = {10.1186/s12864-018-5293-6}, pmid = {30558533}, issn = {1471-2164}, support = {RSA6180075//Thailand Research Fund/ ; PHD60I0014//Thailand Research Fund/ ; PHD60I0082//Thailand Research Fund/ ; MSD60I0035//Thailand Research Fund/ ; GA/PhD/Sup/Year4/003//the Thailand Research Fund - Newton Fund Placement, Travel Grant for PhD Supervisors/ ; 80.60//Kasetsart University Research and Development Institute/ ; 0513.10109/8384//the Fellowship of Capacity Building for Kasetsart University on Internationalization at Kasetsart University/ ; -//the Center for Advanced Studies in Tropical Natural Resources, National Research University-Kasetsart University/ ; 2560096003012//the National Research Council of Thailand/ ; -//the Center of Excellence on Agricultural Biotechnology, Science and Technology Postgraduate Education and Research Development Office, Office of Higher Education Commission, Ministry of Education/ ; BB/K008161/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Unlike the chromosome constitution of most snakes (2n=36), the cobra karyotype shows a diploid chromosome number of 38 with a highly heterochromatic W chromosome and a large morphologically different chromosome 2. To investigate the process of sex chromosome differentiation and evolution between cobras, most snakes, and other amniotes, we constructed a chromosome map of the Siamese cobra (Naja kaouthia) with 43 bacterial artificial chromosomes (BACs) derived from the chicken and zebra finch libraries using the fluorescence in situ hybridization (FISH) technique, and compared it with those of the chicken, the zebra finch, and other amniotes.

RESULTS: We produced a detailed chromosome map of the Siamese cobra genome, focusing on chromosome 2 and sex chromosomes. Synteny of the Siamese cobra chromosome 2 (NKA2) and NKAZ were highly conserved among snakes and other squamate reptiles, except for intrachromosomal rearrangements occurring in NKA2. Interestingly, twelve BACs that had partial homology with sex chromosomes of several amniotes were mapped on the heterochromatic NKAW as hybridization signals such as repeat sequences. Sequence analysis showed that most of these BACs contained high proportions of transposable elements. In addition, hybridization signals of telomeric repeat (TTAGGG)n and six microsatellite repeat motifs ((AAGG)8, (AGAT)8, (AAAC)8, (ACAG)8, (AATC)8, and (AAAAT)6) were observed on NKAW, and most of these were also found on other amniote sex chromosomes.

CONCLUSIONS: The frequent amplification of repeats might involve heterochromatinization and promote sex chromosome differentiation in the Siamese cobra W sex chromosome. Repeat sequences are also shared among amniote sex chromosomes, which supports the hypothesis of an ancestral super-sex chromosome with overlaps of partial syntenies. Alternatively, amplification of microsatellite repeat motifs could have occurred independently in each lineage, representing convergent sex chromosomal differentiation among amniote sex chromosomes.}, } @article {pmid30558532, year = {2018}, author = {Boldi, P and Frasca, M and Malchiodi, D}, title = {Correction to: Evaluating the impact of topological protein features on the negative examples selection.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {530}, doi = {10.1186/s12859-018-2545-z}, pmid = {30558532}, issn = {1471-2105}, abstract = {After publication of the original article [1], it was noticed that the dagger symbol indicating equal contribution wasn't added next to the names of all authors.}, } @article {pmid30558531, year = {2018}, author = {Johansson, LF and de Weerd, HA and de Boer, EN and van Dijk, F and Te Meerman, GJ and Sijmons, RH and Sikkema-Raddatz, B and Swertz, MA}, title = {NIPTeR: an R package for fast and accurate trisomy prediction in non-invasive prenatal testing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {531}, doi = {10.1186/s12859-018-2557-8}, pmid = {30558531}, issn = {1471-2105}, support = {CVON-2011-19//Genius/ ; 917.164.455//NWO VIDI/ ; }, mesh = {*Algorithms ; Female ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Maternal Serum Screening Tests ; Predictive Value of Tests ; Pregnancy ; Prenatal Diagnosis/*methods ; Trisomy/*diagnosis ; }, abstract = {BACKGROUND: Various algorithms have been developed to predict fetal trisomies using cell-free DNA in non-invasive prenatal testing (NIPT). As basis for prediction, a control group of non-trisomy samples is needed. Prediction accuracy is dependent on the characteristics of this group and can be improved by reducing variability between samples and by ensuring the control group is representative for the sample analyzed.

RESULTS: NIPTeR is an open-source R Package that enables fast NIPT analysis and simple but flexible workflow creation, including variation reduction, trisomy prediction algorithms and quality control. This broad range of functions allows users to account for variability in NIPT data, calculate control group statistics and predict the presence of trisomies.

CONCLUSION: NIPTeR supports laboratories processing next-generation sequencing data for NIPT in assessing data quality and determining whether a fetal trisomy is present. NIPTeR is available under the GNU LGPL v3 license and can be freely downloaded from https://github.com/molgenis/NIPTeR or CRAN.}, } @article {pmid30558530, year = {2018}, author = {Mihaljević, B and Larrañaga, P and Benavides-Piccione, R and Hill, S and DeFelipe, J and Bielza, C}, title = {Towards a supervised classification of neocortical interneuron morphologies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {511}, doi = {10.1186/s12859-018-2470-1}, pmid = {30558530}, issn = {1471-2105}, support = {720270//Horizon 2020 Framework Programme/ ; C080020-09//Ministerio de Economía y Competitividad/ ; S2013/ICE-2845-CASI-CAM-CM//Consejería de Educación, Juventud y Deporte, Comunidad de Madrid (ES)/ ; }, mesh = {*Algorithms ; Animals ; Cells, Cultured ; Dendrites/*chemistry ; Interneurons/*classification/*cytology ; Male ; Neocortex/*cytology ; Rats ; Rats, Wistar ; }, abstract = {BACKGROUND: The challenge of classifying cortical interneurons is yet to be solved. Data-driven classification into established morphological types may provide insight and practical value.

RESULTS: We trained models using 217 high-quality morphologies of rat somatosensory neocortex interneurons reconstructed by a single laboratory and pre-classified into eight types. We quantified 103 axonal and dendritic morphometrics, including novel ones that capture features such as arbor orientation, extent in layer one, and dendritic polarity. We trained a one-versus-rest classifier for each type, combining well-known supervised classification algorithms with feature selection and over- and under-sampling. We accurately classified the nest basket, Martinotti, and basket cell types with the Martinotti model outperforming 39 out of 42 leading neuroscientists. We had moderate accuracy for the double bouquet, small and large basket types, and limited accuracy for the chandelier and bitufted types. We characterized the types with interpretable models or with up to ten morphometrics.

CONCLUSION: Except for large basket, 50 high-quality reconstructions sufficed to learn an accurate model of a type. Improving these models may require quantifying complex arborization patterns and finding correlates of bouton-related features. Our study brings attention to practical aspects important for neuron classification and is readily reproducible, with all code and data available online.}, } @article {pmid30558529, year = {2018}, author = {Harvey, AC and Skilbrei, OT and Besnier, F and Solberg, MF and Sørvik, AE and Glover, KA}, title = {Implications for introgression: has selection for fast growth altered the size threshold for precocious male maturation in domesticated Atlantic salmon?.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {188}, doi = {10.1186/s12862-018-1294-y}, pmid = {30558529}, issn = {1471-2148}, abstract = {BACKGROUND: Mature male parr (MMP) represent an important alternative life-history strategy in Atlantic salmon populations. Previous studies indicate that the maturation size threshold for male parr varies among wild populations and is influenced by individual growth, environmental conditions, and genetics. More than ten generations of breeding have resulted in domesticated salmon displaying many genetic differences to wild salmon, including greatly increased growth rates. This may have resulted in domesticated fish with the potential to outgrow the size threshold for early maturation, or evolution of the size threshold of the trait itself. To investigate this, we performed a common-garden experiment under farming conditions using 4680 salmon from 39 families representing four wild, two wild-domesticated hybrid, and two domesticated strains.

RESULTS: Domesticated salmon outgrew wild salmon 2-5-fold, and hybrids displayed intermediate growth. Overall, the numbers of MMP varied greatly among families and strains: averaging 4-12% in domesticated, 18-25% in hybrid, and 43-74% in the wild populations. However, when the influence of growth was accounted for, by dividing fish into lower and upper size modes, no difference in the incidence of MMP was detected among domesticated and wild strains in either size mode. In the lower size mode, hybrids displayed significantly lower incidences of mature males than their wild parental strains. No consistent differences in the body size of MMP, connected to domestication, was detected.

CONCLUSIONS: Our data demonstrate: 1- no evidence for the evolution of the size threshold for MMP in domesticated salmon, 2- the vastly lower incidence of MMP in domesticated strains under aquaculture conditions is primarily due to their genetically increased growth rate causing them to outgrow the size threshold for early maturation, 3- the incidence of MMP is likely to overlap among domesticated and wild salmon in the natural habitat where they typically display overlapping growth, although hybrid offspring may display lower incidences of mature male parr. These results have implications for wild salmon populations that are exposed to introgression from domesticated escapees.}, } @article {pmid30558528, year = {2018}, author = {Azaiez, A and Pavy, N and Gérardi, S and Laroche, J and Boyle, B and Gagnon, F and Mottet, MJ and Beaulieu, J and Bousquet, J}, title = {A catalog of annotated high-confidence SNPs from exome capture and sequencing reveals highly polymorphic genes in Norway spruce (Picea abies).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {942}, doi = {10.1186/s12864-018-5247-z}, pmid = {30558528}, issn = {1471-2164}, abstract = {BACKGROUND: Norway spruce [Picea abies (L.) Karst.] is ecologically and economically one of the most important conifer worldwide. Our main goal was to develop a large catalog of annotated high confidence gene SNPs that should sustain the development of genomic tools for the conservation of natural and domesticated genetic diversity resources, and hasten tree breeding efforts in this species.

RESULTS: Targeted sequencing was achieved by capturing P. abies exome with probes previously designed from the sequenced transcriptome of white spruce (Picea glauca (Moench) Voss). Capture efficiency was high (74.5%) given a high level of exome conservation between the two species. Using stringent criteria, we delimited a set of 61,771 high-confidence SNPs across 13,543 genes. To validate SNPs, a high-throughput genotyping array was developed for a subset of 5571 predicted SNPs representing as many different gene loci, and was used to genotype over 1000 trees. The estimated true positive rate of the resource was 84.2%, which was comparable with the genotyping success rate obtained for P. abies control SNPs recycled from previous genotyping efforts. We also analyzed SNP abundance across various gene functional categories. Several GO terms and gene families involved in stress response were found over-represented in highly polymorphic genes.

CONCLUSION: The annotated high-confidence SNP catalog developed herein represents a valuable genomic resource, being representative of over 13 K genes distributed across the P. abies genome. This resource should serve a variety of population genomics and breeding applications in Norway spruce.}, } @article {pmid30558527, year = {2018}, author = {Pandey, P and Wang, M and Baldwin, IT and Pandey, SP and Groten, K}, title = {Complex regulation of microRNAs in roots of competitively-grown isogenic Nicotiana attenuata plants with different capacities to interact with arbuscular mycorrhizal fungi.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {937}, doi = {10.1186/s12864-018-5338-x}, pmid = {30558527}, issn = {1471-2164}, support = {293926//H2020 European Research Council/ ; Max Planck Partner Group//Max-Planck-Gesellschaft/ ; }, abstract = {BACKGROUND: Nicotiana attenuata is an ecological model plant whose 2.57 Gb genome has recently been sequenced and assembled and for which miRNAs and their genomic locations have been identified. To understand how this plant's miRNAs are reconfigured during plant-arbuscular mycorrhizal fungal (AMF) interactions and whether hostplant calcium- and calmodulin dependent protein kinase (CCaMK) expression which regulates the AMF interaction also modulates miRNAs levels and regulation, we performed a large-scale miRNA analysis of this plant-AMF interaction.

RESULTS: Next generation sequencing of miRNAs in roots of empty vector (EV) N. attenuata plants and an isogenic line silenced in CCaMK expression (irCCaMK) impaired in AMF-interactions grown under competitive conditions with and without AMF inoculum revealed a total of 149 unique miRNAs: 67 conserved and 82 novel ones. The majority of the miRNAs had a length of 21 nucleotides. MiRNA abundances were highly variable ranging from 400 to more than 25,000 reads per million. The miRNA profile of irCCaMK plants impaired in AMF colonization was distinct from fully AMF-functional EV plants grown in the same pot. Six conserved miRNAs were present in all conditions and accumulated differentially depending on treatment and genotype; five (miR6153, miR403a-3p, miR7122a, miR167-5p and miR482d, but not miR399a-3p) showed the highest accumulation in AMF inoculated EV plants compared to inoculated irCCaMK plants. Furthermore, the accumulation patterns of sequence variants of selected conserved miRNAs showed a very distinct pattern related to AMF colonization - one variant of miR473-5p specifically accumulated in AMF-inoculated plants. Also abundances of miR403a-3p, miR171a-3p and one of the sequence variants of miR172a-3p increased in AMF-inoculated EV compared to inoculated irCCaMK plants and to non-inoculated EV plants, while miR399a-3p was most strongly enriched in AMF inoculated irCCaMK plants grown in competition with EV. The analysis of putative targets of selected miRNAs revealed an involvement in P starvation (miR399), phytohormone signaling (Nat-R-PN59, miR172, miR393) and defense (e.g. miR482, miR8667, Nat-R-PN-47).

CONCLUSIONS: Our study demonstrates (1) a large-scale reprograming of miRNAs induced by AMF colonization and (2) that the impaired AMF signaling due to CCaMK silencing and the resulting reduced competitive ability of irCCaMK plants play a role in modulating signal-dependent miRNA accumulation.}, } @article {pmid30558444, year = {2018}, author = {Shaver, JH and Lang, M and Krátký, J and Klocová, EK and Kundt, R and Xygalatas, D}, title = {The Boundaries of Trust: Cross-Religious and Cross-Ethnic Field Experiments in Mauritius.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918817644}, doi = {10.1177/1474704918817644}, pmid = {30558444}, issn = {1474-7049}, abstract = {Several prominent evolutionary theories contend that religion was critical to the emergence of large-scale societies and encourages cooperation in contemporary complex groups. These theories argue that religious systems provide a reliable mechanism for finding trustworthy anonymous individuals under conditions of risk. In support, studies find that people displaying cues of religious identity are more likely to be trusted by anonymous coreligionists. However, recent research has found that displays of religious commitment can increase trust across religious divides. These findings are puzzling from the perspective that religion emerges to regulate coalitions. To date, these issues have not been investigated outside of American undergraduate samples nor have studies considered how religious identities interact with other essential group-membership signals, such as ancestry, to affect intergroup trust. Here, we address these issues and compare religious identity, ancestry, and trust among and between Christians and Hindus living in Mauritius. Ninety-seven participants rated the trustworthiness of faces, and in a modified trust game distributed money among these faces, which varied according to religious and ethnic identity. In contrast to previous research, we find that markers of religious identity increase monetary investments only among in-group members and not across religious divides. Moreover, out-group religious markers on faces of in-group ancestry decrease reported trustworthiness. These findings run counter to recent studies collected in the United States and suggest that local socioecologies influence the relationships between religion and trust. We conclude with suggestions for future research and a discussion of the challenges of conducting field experiments with remote populations.}, } @article {pmid30556805, year = {2018}, author = {Zhu, HZ and Jiang, CY and Liu, SJ}, title = {Crenobacter cavernae sp. nov., isolated from a karst cave, and emended description of the genus Crenobacter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003179}, pmid = {30556805}, issn = {1466-5034}, abstract = {A Gram-stain-negative, rod-shaped, motile and strictly aerobic novel bacterial isolate, designated strain K1W11S-77T, was obtained from a water sample that was collected from a karst cave in Guizhou province, PR China. The results of a phylogenetic analysis based on 16S rRNA gene sequences indicated that K1W11S-77T represented a member of the genus Crenobacter within the family Neisseriaceae of the phylum Proteobacteria. K1W11S-77T was phylogenetically closely related to Crenobacter luteusYIM 78141T (Their 16S rRNA gene sequence similarity is 95.02 %). Growth of K1W11S-77T occurred at 10-30 °C, at pH 7-9, and in the presence of 0-1 % (w/v) NaCl. The major cellular fatty acids were C12 : 0, C16 : 0, C18:1ω7c and summed feature 3. The major isoprenoid quinone was Q-8. The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and one unidentified phospholipid. The genome of K1W11S-77T was 3.27 Mb long and encoded 3167 annotated genes. The DNA G+C content of the genomic DNA was 65.3 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, K1W11S-77T is considered to represent a novel species of the genus Crenobacter, for which the name Crenobactercavernae sp. nov. is proposed. The type strain is K1W11S-77T (=CGMCC 1.13527T=NBRC 113452T).}, } @article {pmid30556804, year = {2018}, author = {Braun, MS and Wang, E and Zimmermann, S and Wagner, H and Wink, M}, title = {Kocuria tytonis sp. nov., isolated from the uropygial gland of an American barn owl (Tyto furcata).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003170}, pmid = {30556804}, issn = {1466-5034}, abstract = {Avian uropygial glands have received increasing attention in recent years, but little is known about micro-organisms in uropygial glands. In this study, we isolated a strain of Gram-stain-positive, non-motile, non-spore-forming cocci, designated 442T, from the uropygial gland of an American barn owl (Tyto furcata) and characterized it using a polyphasic approach. 16S rRNA gene sequence analysis placed the isolate in the genus Kocuria. The G+C content was 70.8 mol%, the major menaquinone was MK-7(H2) and the predominant cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C15 : 0. Phylogenetic analyses based on the 16S rRNA gene identified Kocuria rhizophila DSM 11926T (99.6 % similarity), Kocuria salsicia DSM 24776T (98.7 %), Kocuria varians DSM 20033T (98.3 %) and Kocuria marina DSM 16420T (98.3 %) as the most closely related species. However, average nucleotide identity values below 86 % indicated that the isolate differed from all species hitherto described. Chemotaxonomic analyses and whole-cell protein profiles corroborated these findings. Accordingly, the isolate is considered to be a member of a novel species, for which the name Kocuria tytonis sp. nov. is proposed. The type strain is 442T (=DSM 104130T=LMG 29944T).}, } @article {pmid30556802, year = {2018}, author = {Niemhom, N and Chutrakul, C and Suriyachadkun, C and Tadtong, S and Thawai, C}, title = {Jiangella endophytica sp. nov., an endophytic actinomycete isolated from the rhizome of Kaempferia elegans.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003175}, pmid = {30556802}, issn = {1466-5034}, abstract = {An endophytic actinobacterium, designated strain KE2-3T, was isolated from surface-sterilised rhizome of Kaempferia elegans. The polyphasic approach was used for evaluating the taxonomic position of this strain. The taxonomic affiliation of this strain at genus level could be confirmed by its chemotaxonomic characteristic, i.e. the presence of ll-diaminopimelic acid in the cell peptidoglycan, MK-9(H4) as the major menaquinone, iso-C16 : 0, anteiso-C15 : 0, iso-C14 : 0 and iso-C15 : 0 as the predominant fatty acids in cells, and the presence of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside in its membranes. Based on 16S rRNA gene sequence analysis, strain KE2-3T was identified as a member of the genus Jiangella and showed the highest similarities to Jiangella muralis DSM 45357T (99.3 %) followed by Jiangella albaDSM 45237T (99.2 %), Jiangella alkaliphilia DSM 45079T (99.0 %), Jiangella gansuensisDSM 44835T (98.8 %) and Jiangella mangrovi3SM4-07T (98.6 %). However, the draft genome sequence of strain KE2-3T exhibited low average nucleotide identity values to the reference strains (85.5-90.2 %), which were well below the 95-96 % species circumscription threshold. The DNA G+C content of genomic DNA was 72.3 mol%. With the differences of physiological, biochemical and genotypic data, strain KE2-3T could be discriminated from its closest neighbour. Thus, strain KE2-3T should be recognised as a novel species of genus Jiangella, for which the name Jiangellaendophytica sp. nov. is proposed. The type strain is KE2-3T (=BCC 66359T=NBRC 110004T).}, } @article {pmid30556801, year = {2018}, author = {Sun, Y and Liu, WH and Ai, MJ and Su, J and Yu, LY and Zhang, YQ}, title = {Aeromicrobium lacus sp. nov., a novel actinobacterium isolated from a drinking-water reservoir.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003181}, pmid = {30556801}, issn = {1466-5034}, abstract = {An actinobacterial strain, designated CPCC 204604T, was isolated from a water sample collected from Sancha Lake, a drinking-water reservoir in Sichuan Province, south-west China. Cells were strictly aerobic, Gram-stain-positive, non-spore-forming and non-motile. Polyphasic taxonomic analysis indicated that galactose and ribose were detected as the diagnostic sugars in the whole-cell hydrolysates, and ll-diaminopimelic acid was the diagnostic diamino acid in cell-wall peptidoglycan. MK-9(H4) was the predominant menaquinone. The phospholipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid. The major fatty acids were C16 : 0, C16 : 0 2-OH, C18 : 1ω9c, C18 : 0 and 10-methyl C18:0. The genomic DNA G+C content was 71.2 mol%. In the phylogenetic tree based on 16S rRNA gene sequences, strain CPCC 204604T formed a distinct clade with Aeromicrobium ponti DSM 19178T within the lineage of the genus Aeromicrobium, with the highest 16S rRNA gene sequence similarity of 98.3 % to its closest neighbour. On the basis of the genotypic and phenotypic data, we conclude that strain CPCC 204604T represents a novel species of the genus Aeromicrobium, for which the name Aeromicrobiumlacus sp. nov. is proposed with strain CPCC 204604T (=NBRC 112936T=DSM 105424T) as the type strain.}, } @article {pmid30556800, year = {2018}, author = {Oren, A and Garrity, GM and Spring, S and Onrust, L and Petzoldt, D and Eeckhaut, V and De Maesschalck, C and Haesebrouck, F and Rautenschlein, S and Ducatelle, R and Van Immerseel, F and Taras, D}, title = {Valid publication of the names Caecibacterium and Caecibacterium sporoformans.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003173}, pmid = {30556800}, issn = {1466-5034}, abstract = {Descriptions of the genus Caecibacterium and its proposed type species Caecibacterium sporoformans were published in the IJSEM by Onrust et al. (Int J Syst Evol Microbiol 2017;67:4589-4594). The type strain was deposited as LMG 27730 and DSM 26959. DSM 26959 is a patent strain, and therefore the names were effectively, but not validly, published based on Rule 30(4) of the International Code of Nomenclature of Prokaryotes. The type strain of C. sporoformans is now available from the Deutsche Sammlung von Mikroorganismen und Zellkulturen as DSM 103070 and no restrictions have been placed on its distribution. We here present new descriptions of the genus and its type species so that the names can be validly published.}, } @article {pmid30556639, year = {2018}, author = {Alves Feliciano, C and Douché, T and Giai Gianetto, Q and Matondo, M and Martin-Verstraete, I and Dupuy, B}, title = {CotL, a new morphogenetic spore coat protein of Clostridium difficile.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14505}, pmid = {30556639}, issn = {1462-2920}, abstract = {The strict anaerobe Clostridium difficile is the most common cause of antibiotic-associated diarrhoea. The oxygen-resistant C. difficile spores play a central role in the infectious cycle, contributing to transmission, infection and recurrence. The spore surface layers, the coat and exosporium, enable the spores to resist physical and chemical stress. However, little is known about the mechanisms of their assembly. In this study, we characterized a new spore protein, CotL, which is required for the assembly of the spore coat. The cotL gene was expressed in the mother cell compartment under the dual control of the RNA polymerase sigma factors, σE and σK . CotL was localized in the spore coat, and the spores of the cotL mutant had a major morphologic defect at the level of the coat/exosporium layers. Therefore, the mutant spores contained a reduced amount of several coat/exosporium proteins and a defect in their localization in sporulating cells. Finally, cotL mutant spores were more sensitive to lysozyme and were impaired in germination, a phenotype likely to be associated with the structurally altered coat. Collectively, these results strongly suggest that CotL is a morphogenetic protein essential for the assembly of the spore coat in C. difficile. This article is protected by copyright. All rights reserved.}, } @article {pmid30556587, year = {2018}, author = {Ramakers, JJC and Gienapp, P and Visser, ME}, title = {Phenological mismatch drives selection on elevation, but not on slope, of breeding time plasticity in a wild songbird.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13660}, pmid = {30556587}, issn = {1558-5646}, support = {339092- E-Response//H2020 European Research Council/ ; }, abstract = {Phenotypic plasticity is an important mechanism for populations to respond to fluctuating environments, yet may be insufficient to adapt to a directionally changing environment. To study whether plasticity can evolve under current climate change, we quantified selection and genetic variation in both the elevation (RNE) and slope (RNS) of the breeding time reaction norm in a long-term (1973-2016) study population of great tits (Parus major). The optimal RNE (the caterpillar biomass peak date regressed against the temperature used as cue by great tits) changed over time, whereas the optimal RNS did not. Concordantly, we found strong directional selection on RNE , but not RNS , of egg-laying date in the second third of the study period; this selection subsequently waned, potentially due to increased between-year variability in optimal laying dates. We found individual and additive genetic variation in RNE but, contrary to previous studies on our population, not in RNS . The predicted and observed evolutionary change in RNE was, however, marginal, due to low heritability and the sex limitation of laying date. We conclude that adaptation to climate change can only occur via micro-evolution of RNE, but this will necessarily be slow and potentially hampered by increased variability in phenotypic optima.}, } @article {pmid30556305, year = {2019}, author = {Shapiro, BJ}, title = {Reuniting ecology and evolution.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {13-14}, doi = {10.1111/1758-2229.12703}, pmid = {30556305}, issn = {1758-2229}, } @article {pmid30556304, year = {2018}, author = {Otani, S and Zhukova, M and Koné, NA and da Costa, RR and Mikaelyan, A and Sapountzis, P and Poulsen, M}, title = {Gut microbial compositions mirror caste-specific diets in a major lineage of social insects.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12728}, pmid = {30556304}, issn = {1758-2229}, support = {4075-4956//British Ecological Society/ ; BEX: 13240/13-7//CAPES Foundation, Ministry of Education of Brazil, Brasília, Brazil/ ; 660255//H2020 Marie Skłodowska-Curie Actions/ ; 10101//Villum Fonden/ ; }, abstract = {Social insects owe their ecological success to the division of labour between castes, but associations between microbial community compositions and castes with different tasks and diets have not been extensively explored. Fungus-growing termites associate with fungi to degrade plant material, complemented by diverse gut microbial communities. Here, we explore whether division of labour and accompanying dietary differences between fungus-growing termite castes are linked to gut bacterial community structure. Using amplicon sequencing, we characterize community compositions in sterile (worker and soldier) and reproductive (queen and king) termites and combine this with gut enzyme activities and microscopy to hypothesise sterile caste-specific microbiota roles. Gut bacterial communities are structured primarily according to termite caste and genus and, in contrast to the observed rich and diverse sterile caste microbiotas, royal pair guts are dominated by few bacterial taxa, potentially reflecting their specialized uniform diet and unique lifestyle.}, } @article {pmid30556271, year = {2018}, author = {Radisavljevic, N and Cirstea, M and Brett Finlay, B}, title = {Bottoms up: the role of gut microbiota in brain health.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14506}, pmid = {30556271}, issn = {1462-2920}, support = {//Canadian Institutes of Health Research/ ; }, abstract = {The gut microbiota affects many aspects of human health, and research, especially over the past decade, is demonstrating that the brain is no exception. This review summarizes existing human observational studies of the microbiota in brain health and neurological conditions at all ages, as well as animal studies that are advancing the field beyond correlation and into causality. Potential mechanisms by which the brain and the gut microbiota are connected are explored, including inflammation, bacterially-produced metabolites and neurotransmitters and specific roles for individual microbes. Finally, important challenges and potential mitigation strategies are discussed, as well as ways in which some of these same challenges can be harnessed to advance our understanding of this complex, exciting and rapidly evolving field.}, } @article {pmid30556267, year = {2018}, author = {Zhan, Y and Chen, F}, title = {Bacteriophages that infect marine roseobacters: genomics and ecology.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14504}, pmid = {30556267}, issn = {1462-2920}, abstract = {Viruses are the most abundant biological entities in seawater. They influence microbial population dynamics, genetic heterogeneity and biogeochemical cycles in marine ecosystems. The isolation and characterization of viruses that infect specific hosts have greatly advanced our knowledge of the biological and ecological interactions between viruses and their hosts. Marine Roseobacter are abundant, ubiquitous and diverse in the ocean and play active roles in global biogeochemical cycling, especially the sulfur cycle. Currently, 32 bacteriophages that infect multiple lineages of roseobacters have been isolated and sequenced. These roseophages exhibit diverse morphologies, nucleic acid types and genomic features. Here, we provide the most up-to-date overview of roseophages. Most roseophages are host specific and have a wide range of genome sizes and open reading frames. Based on a genome-wide comparison, at least eight distinctly different types of roseophages were identified, indicating their diversity. Lysogenic-related and gene transfer agent-related genes are commonly found in roseophage genomes, implying the importance of genetic transfer within roseobacters. This feature could provide the versatility for roseobacters to quickly adapt to the changing environments. A wide distribution range of roseophages in the global ocean, especially in coastal environments, has been observed, reflecting the cosmopolitan nature of the Roseobacter lineage.}, } @article {pmid30556094, year = {2018}, author = {Warmerdam, DO and Wolthuis, RMF}, title = {Keeping ribosomal DNA intact: a repeating challenge.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9594-z}, pmid = {30556094}, issn = {1573-6849}, abstract = {More than half of the human genome consists of repetitive sequences, with the ribosomal DNA (rDNA) representing two of the largest repeats. Repetitive rDNA sequences may form a threat to genomic integrity and cellular homeostasis due to the challenging aspects of their transcription, replication, and repair. Predisposition to cancer, premature aging, and neurological impairment in ataxia-telangiectasia and Bloom syndrome, for instance, coincide with increased cellular rDNA repeat instability. However, the mechanisms by which rDNA instability contributes to these hereditary syndromes and tumorigenesis remain unknown. Here, we review how cells govern rDNA stability and how rDNA break repair influences expansion and contraction of repeat length, a process likely associated with human disease. Recent advancements in CRISPR-based genome engineering may help to explain how cells keep their rDNA intact in the near future.}, } @article {pmid30554967, year = {2019}, author = {Sollelis, L and Marti, M}, title = {A Major Step towards Defining the Elusive Stumpy Inducing Factor in Trypanosoma brucei.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {6-8}, doi = {10.1016/j.pt.2018.11.009}, pmid = {30554967}, issn = {1471-5007}, abstract = {Trypanosoma brucei stumpy forms are the only stage that can transmit from human to tsetse fly. Stumpy formation is regulated by a quorum sensing mechanism that depends on parasite density and an unknown stumpy induction factor (SIF). Recently, an elegant study by Matthews and colleagues (Cell 176, 1-12) has identified several crucial components of this pathway, including the putative SIF and its receptor.}, } @article {pmid30554966, year = {2018}, author = {Dantas-Torres, F and Miró, G and Bowman, DD and Gradoni, L and Otranto, D}, title = {Culling Dogs for Zoonotic Visceral Leishmaniasis Control: The Wind of Change.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.005}, pmid = {30554966}, issn = {1471-5007}, abstract = {Visceral leishmaniasis, caused by Leishmania infantum, is a zoonosis, and culling seropositive dogs has been recommended to control the disease in some endemic countries. However, no scientific evidence supports the effectiveness of this strategy to reduce the incidence of visceral leishmaniasis. Economic and ethical issues concerning dog culling are discussed.}, } @article {pmid30554808, year = {2019}, author = {Sutherland, WJ and Broad, S and Butchart, SHM and Clarke, SJ and Collins, AM and Dicks, LV and Doran, H and Esmail, N and Fleishman, E and Frost, N and Gaston, KJ and Gibbons, DW and Hughes, AC and Jiang, Z and Kelman, R and LeAnstey, B and le Roux, X and Lickorish, FA and Monk, KA and Mortimer, D and Pearce-Higgins, JW and Peck, LS and Pettorelli, N and Pretty, J and Seymour, CL and Spalding, MD and Wentworth, J and Ockendon, N}, title = {A Horizon Scan of Emerging Issues for Global Conservation in 2019.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {83-94}, doi = {10.1016/j.tree.2018.11.001}, pmid = {30554808}, issn = {1872-8383}, abstract = {We present the results of our tenth annual horizon scan. We identified 15 emerging priority topics that may have major positive or negative effects on the future conservation of global biodiversity, but currently have low awareness within the conservation community. We hope to increase research and policy attention on these areas, improving the capacity of the community to mitigate impacts of potentially negative issues, and maximise the benefits of issues that provide opportunities. Topics include advances in crop breeding, which may affect insects and land use; manipulations of natural water flows and weather systems on the Tibetan Plateau; release of carbon and mercury from melting polar ice and thawing permafrost; new funding schemes and regulations; and land-use changes across Indo-Malaysia.}, } @article {pmid30554770, year = {2018}, author = {Cordier, T and Lanzén, A and Apothéloz-Perret-Gentil, L and Stoeck, T and Pawlowski, J}, title = {Embracing Environmental Genomics and Machine Learning for Routine Biomonitoring.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.10.012}, pmid = {30554770}, issn = {1878-4380}, abstract = {Genomics is fast becoming a routine tool in medical diagnostics and cutting-edge biotechnologies. Yet, its use for environmental biomonitoring is still considered a futuristic ideal. Until now, environmental genomics was mainly used as a replacement of the burdensome morphological identification, to screen known morphologically distinguishable bioindicator taxa. While prokaryotic and eukaryotic microbial diversity is of key importance in ecosystem functioning, its implementation in biomonitoring programs is still largely unappreciated, mainly because of difficulties in identifying microbes and limited knowledge of their ecological functions. Here, we argue that the combination of massive environmental genomics microbial data with machine learning algorithms can be extremely powerful for biomonitoring programs and pave the way to fill important gaps in our understanding of microbial ecology.}, } @article {pmid30554769, year = {2019}, author = {von Hoven, G and Husmann, M}, title = {Staphylococcus aureus α-Toxin's Close Contacts Ensure the Kill.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {89-90}, doi = {10.1016/j.tim.2018.11.010}, pmid = {30554769}, issn = {1878-4380}, abstract = {The membrane pore-forming α-toxin is an important virulence factor of Staphylococcus aureus. Target cells can remove pores from their surface, but recent work shows that α-toxin may undermine this self-defense by clinging to epithelial cell junctions. The findings could lead to the development of novel remedies against S. aureus infections.}, } @article {pmid30554323, year = {2018}, author = {Jiang, N and Liu, H and Wang, P and Huang, J and Han, H and Wang, Q}, title = {Illumina MiSeq Sequencing Investigation of Microbiota in Bronchoalveolar Lavage Fluid and Cecum of the Swine Infected with PRRSV.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1613-y}, pmid = {30554323}, issn = {1432-0991}, support = {No. 81172777//the National Natural Science Foundation of China under Grant/ ; No. 2014B11NC096//the Dalian Science and Technological Project under Grant/ ; }, abstract = {Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant animal morbidity and mortality and economic losses worldwide. In this study, we analyzed the microbiota in bronchoalveolar lavage fluid (BAL), mucosa, and feces in cecum of the PRRSV-challenged pigs using the Illumina MiSeq sequencing platform, to investigate the role of microbiota in the pathogenesis and development of porcine reproductive and respiratory syndrome (PRRS). Quantitative insights into microbial ecology analyses indicated that the dominant bacterial groups in the lung from the PRRSV-challenged pigs were Haemophilus parasuis and Mycoplasma hyorhinis, with a relative abundance of 35-48% and 27-41%, respectively. Our results were consistent with the clinical observation that the PRRSV-infected pigs are always co-infected with other bacteria, such as Haemophilus and Mycoplasma. On the other hand, Campylobacter and Clostridium became the two most abundant bacteria in the mucosal and luminal microbiota of the cecum of the PRRSV-challenged pigs, and the relative abundance was four times higher than that in the healthy pigs. This suggested that Campylobacter and Clostridium might be associated with the pathogenesis of diarrhea in PRRS. Linear discriminant analysis effect size reveals significant microbial dysbiosis of BAL, mucosa, and feces in cecum of the PRRSV-challenged pigs. We have identified a structural imbalance of the microbiota, characterized by a reduced diversity of microbiota and abundance alterations of certain bacteria in the PRRSV-challenged pigs. The observed microbiota dysbiosis in this study provides insight into the roles of the microbiota in the complications of the PRRSV infection.}, } @article {pmid30553880, year = {2018}, author = {Ansari, MH and Cooper, SJB and Schwarz, MP and Ebrahimi, M and Dolman, G and Reinberger, L and Saint, KM and Donnellan, SC and Bull, CM and Gardner, MG}, title = {Plio-Pleistocene diversification and biogeographic barriers in southern Australia reflected in the phylogeography of a widespread and common lizard species.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {107-119}, doi = {10.1016/j.ympev.2018.12.014}, pmid = {30553880}, issn = {1095-9513}, abstract = {Palaeoclimatic events and biogeographical processes since the mid-Tertiary have played an important role in shaping the evolution and distribution of Australian fauna. However, their impacts on fauna in southern and arid zone regions of Australia are not well understood. Here we investigate the phylogeography of an Australian scincid lizard, Tiliqua rugosa, across southern Australia using mitochondrial DNA (mtDNA) and 11 nuclear DNA markers (nuDNA), including nine anonymous nuclear loci. Phylogenetic analyses revealed three major mtDNA lineages within T. rugosa, geographically localised north and south of the Murray River in southern Australia, and west of the Nullarbor Plain. Molecular variance and population analyses of both mtDNA and nuDNA haplotypes revealed significant variation among the three populations, although potential introgression of nuDNA markers was also detected for the Northern and Southern population. Coalescent times for major mtDNA lineages coincide with an aridification phase, which commenced after the early Pliocene and increased in intensity during the Late Pliocene-Pleistocene. Species distribution modelling and a phylogeographic diffusion model suggest that the range of T. rugosa may have contracted during the Last Glacial Maximum and the locations of optimal habitat appear to coincide with the geographic origin of several distinct mtDNA lineages. Overall, our analyses suggest that Plio-Pleistocene climatic changes and biogeographic barriers associated with the Nullarbor Plain and Murray River have played a key role in shaping the present-day distribution of genetic diversity in T. rugosa and many additional ground-dwelling animals distributed across southern Australia.}, } @article {pmid30553879, year = {2018}, author = {Sudianto, E and Wu, CS and Leonhard, L and Martin, WF and Chaw, SM}, title = {Enlarged and highly repetitive plastome of Lagarostrobos and plastid phylogenomics of Podocarpaceae.}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {24-32}, doi = {10.1016/j.ympev.2018.12.012}, pmid = {30553879}, issn = {1095-9513}, abstract = {Podocarpaceae is the largest family in cupressophytes (conifers II), but its plastid genomes (plastomes) are poorly studied, with plastome data currently existing for only four of the 19 Podocarpaceous genera. In this study, we sequenced and assembled the complete plastomes from representatives of eight additional genera, including Afrocarpus, Dacrydium, Lagarostrobos, Lepidothamnus, Pherosphaera, Phyllocladus, Prumnopitys, and Saxegothaea. We found that Lagarostrobos, a monotypic genus native to Tasmania, has the largest plastome (151,496 bp) among any cupressophytes studied to date. Plastome enlargement in Lagarostrobos coincides with increased intergenic spacers, repeats, and duplicated genes. Among the Podocarpaceae, Lagarostrobos has the most rearranged plastome, but its substitution rates are modest. Plastid phylogenomic analyses based on 81 plastid genes clarify the positions of previously conflicting Podocarpaceous genera. Tree topologies firmly support the division of Podocarpaceae into two sister clades: (1) the Prumnopityoid clade and (2) the clade containing Podocarpoid, Dacrydioid, Pherosphaera, and Saxegothaea. The Phyllocladus is nested within the Podocarpaceae, thus familial status of the monotypic Phyllocladaceae is not supported.}, } @article {pmid30553808, year = {2019}, author = {Anllo, L and Plasschaert, LW and Sui, J and DiNardo, S}, title = {Live imaging reveals hub cell assembly and compaction dynamics during morphogenesis of the Drosophila testis niche.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {102-118}, doi = {10.1016/j.ydbio.2018.12.014}, pmid = {30553808}, issn = {1095-564X}, abstract = {Adult stem cells are often found in specialized niches, where the constituent cells direct self-renewal of their stem cell pool. The niche is therefore crucial for both normal homeostasis and tissue regeneration. In many mammalian tissues, niche cells have classically been difficult to identify, which has hampered any understanding of how tissues first construct niches during development. Fortunately, the Drosophila germline stem cell (GSC) niche is well defined, allowing for unambiguous identification of both niche cells and resident stem cells. The testis niche first forms in the early embryo, during a late stage of gonadogenesis. Here, using live-imaging both in vivo and ex vivo, we follow pro-niche cells as they assemble and assume their final form. We show that after ex vivo culture the niche appears fully functional, as judged by enrichment of adhesion proteins, the ability to activate STAT in adjacent GSCs, and to direct GSCs to divide orthogonally to the niche, just as they would in situ. Collectively, our imaging has generated several novel insights on niche morphogenesis that could not be inferred from fixed images alone. We identify dynamic processes that constitute an assembly phase and a compaction phase during morphogenesis. The compaction phase correlates with cell neighbor exchange among the assembled pro-niche cells, as well as a burst of divisions among newly recruited stem cells. Before compaction, an assembly phase involves the movement of pro-niche cells along the outer periphery of the gonad, using the extracellular matrix (ECM) to assemble at the anterior of the gonad. Finally, live-imaging in integrin mutants allows us to define the role of pro-niche cell-ECM interaction with regard to the new assembly and compaction dynamics revealed here.}, } @article {pmid30553653, year = {2019}, author = {Ma, MJ and Yang, Y and Fang, LQ}, title = {Highly Pathogenic Avian H7N9 Influenza Viruses: Recent Challenges.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {93-95}, doi = {10.1016/j.tim.2018.11.008}, pmid = {30553653}, issn = {1878-4380}, abstract = {Novel highly pathogenic avian influenza (HPAI) H7N9 viruses of the fifth epidemic wave infect humans and poultry. Recently, HPAI H7N9 viruses have evolved into different subtypes and genotypes, exhibited heightened virulence in mammals, and extended their host range, thereby posing a potential threat to public health and the poultry industry.}, } @article {pmid30553552, year = {2019}, author = {Halfon, MS}, title = {Studying Transcriptional Enhancers: The Founder Fallacy, Validation Creep, and Other Biases.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {93-103}, doi = {10.1016/j.tig.2018.11.004}, pmid = {30553552}, issn = {0168-9525}, support = {R01 GM114067/GM/NIGMS NIH HHS/United States ; }, abstract = {Transcriptional enhancers play a major role in regulating metazoan gene expression. Recent developments in genomics and next-generation sequencing have accelerated and revitalized the study of this important class of sequence elements. Increased interest and attention, however, has also led to troubling trends in the enhancer literature. In this Opinion, I describe some of these issues and show how they arise from shifting and nonuniform enhancer definitions, and genome-era biases. I discuss how they can lead to interpretative errors and an unduly narrow focus on certain aspects of enhancer biology to the potential exclusion of others.}, } @article {pmid30553295, year = {2018}, author = {Mäser, P}, title = {Host-Microbe Interactions: Parasitology Vol 46.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {vi-viii}, doi = {10.1016/j.mib.2018.11.008}, pmid = {30553295}, issn = {1879-0364}, } @article {pmid30553294, year = {2018}, author = {Dean, RA and Rouxel, T}, title = {Host-Microbe Interactions: Fungi Vol 46.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {iii-v}, doi = {10.1016/j.mib.2018.11.009}, pmid = {30553294}, issn = {1879-0364}, } @article {pmid30552965, year = {2019}, author = {Yang, L and Kong, H and Huang, JP and Kang, M}, title = {Different species or genetically divergent populations? Integrative species delimitation of the Primulina hochiensis complex from isolated karst habitats.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {219-231}, doi = {10.1016/j.ympev.2018.12.011}, pmid = {30552965}, issn = {1095-9513}, abstract = {To consistently and objectively delineate species-level divergence from population subdivision has been a challenge in systematics. This is particularly evident in naturally fragmented and allopatric systems in which small population size often leads to extreme population structuring. Here we evaluated the robustness of the species delimitation methods implemented in BEAST, BPP, and iBPP in the Primulina hochiensis complex comprising four described and one candidate species (five taxa in total) distributed in karst landscapes of southern China. We analyzed levels of molecular and morphological divergence among species using multilocus sequence data (nine chloroplast loci and 10 nuclear loci), and morphological data (16 quantitative and 12 qualitative traits), for 124 individuals from 25 populations of the complex. Independent analyses of cpDNA and nDNA sequence data revealed high levels of genetic differentiation among the five taxa. Both BPP and iBPP delimited five candidate species, which correspond to the five genetic clusters recovered with population structure analysis. In contrast, morphological differences among populations were more limited, so that results from principal component analysis (PCA) recovered only three distinct clusters. We ruled out the possibility of morphologically cryptic species because reciprocally monophyletic groups were not supported among the morphologically un-differentiated taxa. Our results represent a case where extreme population genetic structuring leads to oversplit of species diversity by molecular data using the multispecies coalescent (MSC) methods. The observed congruence across multiple analyses corroborates the recognition of a new species P. lianpingensis and indicates its sister species relationship with P. yingdeensis. This study highlights the dangers of violating model assumption and the importance of incorporating multiple evidence into species delimitation of a particular system.}, } @article {pmid30552867, year = {2019}, author = {Kurowski, A and Molotkov, A and Soriano, P}, title = {FGFR1 regulates trophectoderm development and facilitates blastocyst implantation.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {94-101}, doi = {10.1016/j.ydbio.2018.12.008}, pmid = {30552867}, issn = {1095-564X}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; R01 DE022778/DE/NIDCR NIH HHS/United States ; }, abstract = {FGF signaling plays important roles in many aspects of mammalian development. Fgfr1-/- and Fgfr1-/-Fgfr2-/- mouse embryos on a 129S4 co-isogenic background fail to survive past the peri-implantation stage, whereas Fgfr2-/- embryos die at midgestation and show defects in limb and placental development. To investigate the basis for the Fgfr1-/- and Fgfr1-/-Fgfr2-/- peri-implantation lethality, we examined the role of FGFR1 and FGFR2 in trophectoderm (TE) development. In vivo, Fgfr1-/- TE cells failed to downregulate CDX2 in the mural compartment and exhibited abnormal apicobasal E-Cadherin polarity. In vitro, we were able to derive mutant trophoblast stem cells (TSCs) from Fgfr1-/- or Fgfr2-/- single mutant, but not from Fgfr1-/-Fgfr2-/- double mutant blastocysts. Fgfr1-/- TSCs however failed to efficiently upregulate TE differentiation markers upon differentiation. These results suggest that while the TE is specified in Fgfr1-/- mutants, its differentiation abilities are compromised leading to defects at implantation.}, } @article {pmid30552427, year = {2018}, author = {}, title = {2018: Choice cuts from this year's News & Views articles.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {356-357}, doi = {10.1038/d41586-018-07686-2}, pmid = {30552427}, issn = {1476-4687}, } @article {pmid30552139, year = {2018}, author = {Yang, Y and Lam, V and Adomako, M and Simkovsky, R and Jakob, A and Rockwell, NC and Cohen, SE and Taton, A and Wang, J and Lagarias, JC and Wilde, A and Nobles, DR and Brand, JJ and Golden, SS}, title = {Phototaxis in a wild isolate of the cyanobacterium Synechococcus elongatus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12378-E12387}, doi = {10.1073/pnas.1812871115}, pmid = {30552139}, issn = {1091-6490}, support = {R35 GM118290/GM/NIGMS NIH HHS/United States ; }, abstract = {Many cyanobacteria, which use light as an energy source via photosynthesis, have evolved the ability to guide their movement toward or away from a light source. This process, termed "phototaxis," enables organisms to localize in optimal light environments for improved growth and fitness. Mechanisms of phototaxis have been studied in the coccoid cyanobacterium Synechocystis sp. strain PCC 6803, but the rod-shaped Synechococcus elongatus PCC 7942, studied for circadian rhythms and metabolic engineering, has no phototactic motility. In this study we report a recent environmental isolate of S. elongatus, the strain UTEX 3055, whose genome is 98.5% identical to that of PCC 7942 but which is motile and phototactic. A six-gene operon encoding chemotaxis-like proteins was confirmed to be involved in phototaxis. Environmental light signals are perceived by a cyanobacteriochrome, PixJSe (Synpcc7942_0858), which carries five GAF domains that are responsive to blue/green light and resemble those of PixJ from Synechocystis Plate-based phototaxis assays indicate that UTEX 3055 uses PixJSe to sense blue and green light. Mutation of conserved functional cysteine residues in different GAF domains indicates that PixJSe controls both positive and negative phototaxis, in contrast to the multiple proteins that are employed for implementing bidirectional phototaxis in Synechocystis.}, } @article {pmid30551869, year = {2018}, author = {Agerbæk, MØ and Bang-Christensen, S and Salanti, A}, title = {Fighting Cancer Using an Oncofetal Glycosaminoglycan-Binding Protein from Malaria Parasites.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.11.004}, pmid = {30551869}, issn = {1471-5007}, abstract = {Malaria research has led to the discovery of oncofetal chondroitin sulfate, which appears to be shared between placental trophoblasts and cancer cells and can be detected by the evolutionary refined malaria protein VAR2CSA. Interestingly, using recombinant VAR2CSA to target oncofetal chondroitin sulfate shows promise for novel cancer diagnostics and therapeutics.}, } @article {pmid30551845, year = {2019}, author = {Wilson, D}, title = {Candida albicans.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {188-189}, doi = {10.1016/j.tim.2018.10.010}, pmid = {30551845}, issn = {1878-4380}, abstract = {Pathogens often face zinc restriction due to the action of nutritional immunity - host processes which restrict microbial access to key micronutrients such as zinc and iron. Candida albicans scavenges environmental zinc via two pathways. The plasma membrane transporter Zrt2 is essential for zinc uptake and growth in acidic environments. Neutralisation to pH 7 severely decreases the solubility of ionic Zn2+; this increase in pH triggers expression and activity of a second zinc scavenging system, the zincophore. This fungus-specific system consists of a secreted zinc-binding protein, Pra1, which captures zinc and returns to the cell via a syntenically expressed receptor, Zrt1. If present in excess, zinc is detoxified via a Zrc1-dependent mechanism. In C. albicans Zrc1 plays an important role in the generation of zincosomes. C. albicans faces both low and high zinc bottlenecks in vivo as Zrt2 and Zrc1 are required for kidney and liver colonisation, respectively, in a murine infection model.}, } @article {pmid30551741, year = {2018}, author = {Andrianaivoarimanana, V and Rajerison, M and Jambou, R}, title = {Exposure to Yersinia pestis increases resistance to plague in black rats and modulates transmission in Madagascar.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {898}, doi = {10.1186/s13104-018-3984-3}, pmid = {30551741}, issn = {1756-0500}, abstract = {OBJECTIVES: In Madagascar, plague (Yersinia pestis infection) is endemic in the central highlands, maintained by the couple Rattus rattus/flea. The rat is assumed to die shortly after infection inducing migration of the fleas. However we previously reported that black rats from endemic areas can survive the infection whereas those from non-endemic areas remained susceptible. We investigate the hypothesis that lineages of rats can acquire resistance to plague and that previous contacts with the bacteria will affect their survival, allowing maintenance of infected fleas. For this purpose, laboratory-born rats were obtained from wild black rats originating either from plague-endemic or plague-free zones, and were challenged with Y. pestis. Survival rate and antibody immune responses were analyzed.

RESULTS: Inoculation of low doses of Y. pestis greatly increase survival of rats to subsequent challenge with a lethal dose. During challenge, cytokine profiles support activation of specific immune response associated with the bacteria control. In addition, F1 rats from endemic areas exhibited higher survival rates than those from non-endemic ones, suggesting a selection of a resistant lineage. In Madagascar, these results support the role of black rat as long term reservoir of infected fleas supporting maintenance of plague transmission.}, } @article {pmid30550965, year = {2019}, author = {Piñeros, VJ and Beltrán-López, RG and Baldwin, CC and Barraza, E and Espinoza, E and Martínez, JE and Domínguez-Domínguez, O}, title = {Diversification of the genus Apogon (Lacepède, 1801) (Apogonidae: Perciformes) in the tropical eastern Pacific.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {232-242}, doi = {10.1016/j.ympev.2018.12.010}, pmid = {30550965}, issn = {1095-9513}, abstract = {We examined the role of geographic barriers and historical processes on the diversification of Apogon species within the tropical eastern Pacific (TEP). Mitochondrial and nuclear DNA sequences were used in Bayesian and Maximum likelihood analyses to generate a phylogenetic hypothesis for Apogon species. Bayesian inferences were used to date the cladogenetic events. Analyses with BioGeoBEARS were conducted to reconstruct the biogeographic history and ancestral ranges. The phylogenetic results show a monophyletic clade of TEP Apogon species with A. imberbis from the eastern Atlantic as sister species. The two lineages diverged during the Miocene. Within the TEP clade, two subclades diverged at around 11.1 million years ago (Mya): one clusters the coastal continental species (A. pacificus, A. retrosella and A. dovii), and the second clusters the oceanic island species (A. atradorsatus, A. atricaudus and A. guadalupensis). The estimated diversification times of these subclades were 9.8 and 7.1 Mya, respectively. Within each subclade, species divergences occurred during the Pliocene-Pleistocene epochs. The divergent event between the Atlantic A. imberbis and Apogon TEP clade corresponds to the first closure event of the Central American Seaway. The biogeographic history of Apogon within the TEP appears to be the result of vicariant, dispersal and founder events that occurred during the last 11 million years. The vicariant and dispersal events occurred along the mainland and were associated with the origin of the Central American Gap. The founder events could have allowed the invasion of Apogon to TEP island areas and could have been driven by ancient warming oceanic waters, changes in circulation of marine currents, and the presence of seamounts in ancient marine ridges that allowed the settlement of marine biota. These factors may have allowed Apogon lineages to cross the TEP biogeographic barriers at different times, with subsequent genetic isolation.}, } @article {pmid30550964, year = {2018}, author = {Lu, NT and Ebihara, A and He, H and Zhang, L and Zhou, XM and Knapp, R and Kamau, P and Lorence, D and Gao, XF and Zhang, LB}, title = {A plastid phylogeny of the fern genus Arachniodes (Dryopteridaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {133}, number = {}, pages = {214-235}, doi = {10.1016/j.ympev.2018.12.013}, pmid = {30550964}, issn = {1095-9513}, abstract = {Arachniodes (Dryopteridaceae) is one of the most confusing and controversial fern genera in terms of its circumscription, nomenclature, and taxonomy. Estimates of species number range from 40 to 200. Previous molecular works included only 2-17 accessions representing 2-12 species of Arachniodes and allied genera, leaving most of the Asian species remain unsampled and the infragneric relationships unclear. In this study DNA sequences of seven plastid markers of 343 accessions representing ca. 68 species of Arachniodes (275 accessions), and 64 outgroup accessions from subfam. Dryopteridoideae and subfam. Polybotryoideae were used to infer a phylogeny with maximum likelihood, Bayesian inference, and maximum parsimony approaches. Our major results include: (1) Two species currently assigned in Arachniodes (A. macrostegia and A. ochropteroides are resolved outside of the core Arachniodes making the currently defined Arachniodes polyphyletic, confirming earlier findings; (2) Lithostegia, Leptorumohra, and Phanerophlebiopsis are indeed synonyms of Arachniodes; (3) Leptorumohra is confirmed to be monophyletic, but Phanerophlebiopsis is polyphyletic; (4) The New World species of Arachniodes are confirmed to be not monophyletic with A. denticulata being nested within the Old World species, suggesting that this species is dispersed from the Old World; (5) Arachniodes s.s is resolved into 12 major clades, some of which are further divisable into recognizable subclades and groups, with A. mutica from Japan being resolved as the sister to the rest of the genus; (6) A number of systematic implications of the phylogeny have been suggested; and (7) the genus is estimated to contain ca. 83 species.}, } @article {pmid30550963, year = {2019}, author = {Horsáková, V and Nekola, JC and Horsák, M}, title = {When is a "cryptic" species not a cryptic species: A consideration from the Holarctic micro-landsnail genus Euconulus (Gastropoda: Stylommatophora).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {307-320}, doi = {10.1016/j.ympev.2018.12.004}, pmid = {30550963}, issn = {1095-9513}, abstract = {Naive use of molecular data may lead to ambiguous conclusions, especially within the context of "cryptic" species. Here, we integrated molecular and morphometric data to evaluate phylogenetic relationships in the widespread terrestrial micro-snail genus, Euconulus. We analyzed mitochondrial (16S + COII) and nuclear (ITS1 + ITS2) sequence across 94 populations from Europe, Asia and North America within the nominate species E. alderi, E. fulvus and E. polygyratus, and used the southeastern USA E. chersinus, E. dentatus, and E. trochulus as comparative outgroups. Phylogeny was reconstructed using four different reconstruction methods to identify robust, well-supported topological features. We then performed discriminant analysis on shell measurements between these genetically-identified species-level clades. These analyses provided evidence for a biologically valid North American "cryptic" species within E. alderi. However, while highly supported polyphyletic structure was also observed within E. fulvus, disagreement in placement of individuals between mtDNA and nDNA clades, lack of morphological differences, and presence of potential hybrids imply that these lineages do not rise to the threshold as biologically valid cryptic species, and rather appear to simply represent a complex of geographically structured populations within a single species. These results caution that entering into a cryptic species hypothesis should not be undertaken lightly, and should be optimally supported along multiple lines of evidence. Generally, post-hoc analyses of macro-scale features should be conducted to attempt identification of previously ignored diagnostic traits. If such traits cannot be found, i.e. in the case of potentially "fully cryptic" species, additional criteria should be met to propound a cryptic species hypothesis, including the agreement in tree topology among both mtDNA and nDNA, and little (or no) evidence of hybridization based on a critical analysis of sequence chromatograms. Even when the above conditions are satisfied, it only implies that the cryptic species hypothesis is plausible, but should optimally be subjected to further careful examination.}, } @article {pmid30550962, year = {2019}, author = {Feng, C and Zhou, W and Tang, Y and Gao, Y and Chen, J and Tong, C and Liu, S and Wanghe, K and Zhao, K}, title = {Molecular systematics of the Triplophysa robusta (Cobitoidea) complex: Extensive gene flow in a depauperate lineage.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {275-283}, doi = {10.1016/j.ympev.2018.12.009}, pmid = {30550962}, issn = {1095-9513}, abstract = {Gene flow between populations assumed to be isolated frequently leads to incorrect inferences of evolutionary history. Understanding gene flow and its causes has long been a key topic in evolutionary biology. In this study, we explored the evolutionary history of the Triplophysa robusta complex, using a combination of multilocus analyses and coalescent simulation. Our multilocus approach detected conspicuous mitonuclear discordances in the T. robusta complex. Mitochondrial results showed reticular clades, whereas the nuclear results corresponded with the morphological data. Coalescent simulation indicated that gene flow was the source of these discordances. Molecular clock analysis combined with geological processes suggest that intense geological upheavals have shaped a complicated evolutionary history for the T. robusta complex since the late Miocene, causing extensive gene flow which has distorted the molecular systematics of the T. robusta complex. We suggest that frequent gene flow may restrict speciation in the T. robusta complex, leading to such a depauperate lineage. Based on this comprehensive understanding, we provide our proposals for taxonomic revision of the T. robusta complex.}, } @article {pmid30550961, year = {2019}, author = {Caro, A and Gómez-Moliner, BJ and Madeira, MJ}, title = {Integrating multilocus DNA data and 3D geometric morphometrics to elucidate species boundaries in the case of Pyrenaearia (Pulmonata: Hygromiidae).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {194-206}, doi = {10.1016/j.ympev.2018.12.007}, pmid = {30550961}, issn = {1095-9513}, abstract = {To accurately delimit species the use of multiple character types is essential as all speciation processes are not equally reflected in different data (e.g. morphological, molecular or ecological characters). With the introduction of geometric morphometrics methods and advances in 3D technology, a comprehensive combination of molecular and morphological data has been enabled in groups where exhaustively quantifying and measuring morphological shape change was not possible before such as gastropod shells. In this study, we combined multilocus coalescent species delimitation methods with 3D geometric morphometrics of shell shape to delimit species within the land snail genus Pyrenaearia. A new taxonomic scheme was constructed for the genus identifying ten species. Two nominal species were synonymized and a hitherto unrecognized cryptic species was identified. Our findings support the importance of combining multiple lines of evidence as molecular and morphological data on their own do not yield the same information. Further, the integration of morphological and molecular data shows the importance of allometry in shell shape and suggests a combined effect of population history and selection in different environments on shells morphological variation. Our new taxonomy and phylogenetic reconstruction suggest that, besides the glacial cycles of the Pleistocene, passive dispersal and rock substrate complexity could also have been involved in the speciation of the genus.}, } @article {pmid30550882, year = {2018}, author = {Lanoue, V and Cooper, HM}, title = {Branching mechanisms shaping dendrite architecture.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.005}, pmid = {30550882}, issn = {1095-564X}, abstract = {A neuron's contribution to the information flow within a neural circuit is governed by the structure of its dendritic arbor. The geometry of the dendritic arbor directly determines synaptic density and the size of the receptive field, both of which influence the firing pattern of the neuron. Importantly, the position of individual dendritic branches determines the identity of the neuron's presynaptic partner and thus the nature of the incoming sensory information. To generate the unique stereotypic architecture of a given neuronal subtype, nascent branches must emerge from the dendritic shaft at preprogramed branch points. Subsequently, a complex array of extrinsic factors regulates the degree and orientation of branch expansion to ensure maximum coverage of the receptive field whilst constraining growth within predetermined territories. In this review we focus on studies that best illustrate how environmental cues such as the Wnts and Netrins and their receptors sculpt the dendritic arbor. We emphasize the pivotal role played by the actin cytoskeleton and its upstream regulators in branch initiation, outgrowth and navigation. Finally, we discuss how protocadherin and DSCAM contact-mediated repulsion prevents inappropriate synapse formation between sister dendrites or dendrites and the axon from the same neuron. Together these studies highlight the clever ways evolution has solved the problem of constructing complex branch geometries.}, } @article {pmid30549265, year = {2018}, author = {Simpson, RK and McGraw, KJ}, title = {Experimental trait mismatches uncover specificity of evolutionary links between multiple signaling traits and their interactions in hummingbirds.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13662}, pmid = {30549265}, issn = {1558-5646}, support = {//Arizona State University (ASU)/ ; //Conservation Biology Research/ ; //National Science Foundation/ ; IOS-1702016//Doctoral Dissertation Improvement/ ; IOS-1702016//Division of Integrative Organismal Systems/ ; //T & E Inc./ ; }, abstract = {Many animal signals co-occur, and these signals may coevolve due to their interactive properties. Previous work has demonstrated ecological drivers of evolutionary relationships between signals and the environment, which leads to questions about why specific signal pairs evolved among species that possess multiple signals. We asked whether the coloration of different species was optimized for presentation with its natural behavioral display. We investigated this in "bee" hummingbirds, where males exhibit angle-dependent structurally-colored plumage and a stereotyped courtship (shuttle) display, by experimentally creating mismatches between the behavior and plumage of five species and quantifying how these mismatches influenced male color appearance during a display. Specifically, we photographed the plumage from a given species as we moved its feathers through the position-and-orientation-specific courtship display path of other species and quantified the resulting color appearance during the display in order to compare the mismatched color appearance to each species' natural color appearance. We found that mismatches significantly altered display flashiness (% change in coloration during displays) compared to the natural plumage-behavior pairings, and that such departures in flashiness were predicted by differences in shuttle behaviors alone. These results illustrate a tight evolutionary relationship between shuttle displays and color flashiness in these hummingbirds. Further, we found that interspecific variation in male plumage, behavior, and natural color appearance predicted deviations between natural and mismatched flashy color appearance. Altogether, our work provides a new method for testing signal coevolution and highlights the complex evolutionary relationships between multiple signals and their interactions.}, } @article {pmid30549262, year = {2018}, author = {Rudin, FS and Simmons, LW and Tomkins, JL}, title = {Social cues affect quantitative genetic variation and covariation in animal personality traits.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13661}, pmid = {30549262}, issn = {1558-5646}, support = {//Australian Government Research Training Program Scholarship/ ; DP110104594//Australian Research Council/ ; FT110100500//Australian Research Council/ ; //The University of Western Australia (School of Biological Sciences)/ ; }, abstract = {The social environment is expected to have substantial effects on behavior, and as a consequence, its heritability and evolvability. We investigated these effects by exposing Australian field crickets (Teleogryllus oceanicus) to either silence or recordings of male acoustic sexual signals. We used a combined pedigree and full-sib/half-sib breeding design to estimate the repeatability, heritability, and evolvability of behaviors related to boldness, exploration, and activity. All behaviors measured were significantly repeatable in both social environments. Additionally, most behaviors showed significant heritabilities in the two environments. We found no difference in repeatabilities between the silent and the acoustic environment but did find significant differences in the heritabilities and evolvabilities between these environments. There was a high degree of similarity between the phenotypic covariance matrices across the two environments, while the genotypic covariance matrices were highly dissimilar. Reflecting this, we found significant genotype-by-environment interactions for most of the behaviors. Lastly, we found that the repeatable aspect of behavior ("personality") was significantly heritable for most behaviors, but that these heritabilities were higher in the acoustic than in the silent environment. We conclude that the social environment can have a significant impact on the heritability and evolvability of behavior, and argue that evolutionary inferences from phenotypic studies should be made with caution.}, } @article {pmid30549260, year = {2018}, author = {Haaland, TR and Wright, J and Tufto, J and Ratikainen, II}, title = {Short-term insurance versus long-term bet-hedging strategies as adaptations to variable environments.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13659}, pmid = {30549260}, issn = {1558-5646}, support = {223257//Norges Forskningsråd/ ; 240008//Norges Forskningsråd/ ; }, abstract = {Understanding how organisms adapt to environmental variation is a key challenge of biology. Central to this are bet-hedging strategies that maximize geometric mean fitness across generations, either by being conservative or diversifying phenotypes. Theoretical models have identified environmental variation across generations with multiplicative fitness effects as driving the evolution of bet-hedging. However, behavioral ecology has revealed adaptive responses to additive fitness effects of environmental variation within lifetimes, either through insurance or risk-sensitive strategies. Here, we explore whether the effects of adaptive insurance interact with the evolution of bet-hedging by varying the position and skew of both arithmetic and geometric mean fitness functions. We find that insurance causes the optimal phenotype to shift from the peak to down the less steeply decreasing side of the fitness function, and that conservative bet-hedging produces an additional shift on top of this, which decreases as adaptive phenotypic variation from diversifying bet-hedging increases. When diversifying bet-hedging is not an option, environmental canalization to reduce phenotypic variation is almost always favored, except where the tails of the fitness function are steeply convex and produce a novel risk-sensitive increase in phenotypic variance akin to diversifying bet-hedging. Importantly, using skewed fitness functions, we provide the first model that explicitly addresses how conservative and diversifying bet-hedging strategies might coexist.}, } @article {pmid30548772, year = {2018}, author = {Wackett, LP}, title = {Bacteria and oxidative stress: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4629-4630}, doi = {10.1111/1462-2920.14495}, pmid = {30548772}, issn = {1462-2920}, } @article {pmid30548743, year = {2018}, author = {Wong, MKL and Guénard, B and Lewis, OT}, title = {Trait-based ecology of terrestrial arthropods.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12488}, pmid = {30548743}, issn = {1469-185X}, support = {//Clarendon Scholarship from the University of Oxford/ ; NE/N010221/1//NERC/ ; }, abstract = {In focusing on how organisms' generalizable functional properties (traits) interact mechanistically with environments across spatial scales and levels of biological organization, trait-based approaches provide a powerful framework for attaining synthesis, generality and prediction. Trait-based research has considerably improved understanding of the assembly, structure and functioning of plant communities. Further advances in ecology may be achieved by exploring the trait-environment relationships of non-sessile, heterotrophic organisms such as terrestrial arthropods, which are geographically ubiquitous, ecologically diverse, and often important functional components of ecosystems. Trait-based studies and trait databases have recently been compiled for groups such as ants, bees, beetles, butterflies, spiders and many others; however, the explicit justification, conceptual framework, and primary-evidence base for the burgeoning field of 'terrestrial arthropod trait-based ecology' have not been well established. Consequently, there is some confusion over the scope and relevance of this field, as well as a tendency for studies to overlook important assumptions of the trait-based approach. Here we aim to provide a broad and accessible overview of the trait-based ecology of terrestrial arthropods. We first define and illustrate foundational concepts in trait-based ecology with respect to terrestrial arthropods, and justify the application of trait-based approaches to the study of their ecology. Next, we review studies in community ecology where trait-based approaches have been used to elucidate how assembly processes for terrestrial arthropod communities are influenced by niche filtering along environmental gradients (e.g. climatic, structural, and land-use gradients) and by abiotic and biotic disturbances (e.g. fire, floods, and biological invasions). We also review studies in ecosystem ecology where trait-based approaches have been used to investigate biodiversity-ecosystem function relationships: how the functional diversity of arthropod communities relates to a host of ecosystem functions and services that they mediate, such as decomposition, pollination and predation. We then suggest how future work can address fundamental assumptions and limitations by investigating trait functionality and the effects of intraspecific variation, assessing the potential for sampling methods to bias the traits and trait values observed, and enhancing the quality and consolidation of trait information in databases. A roadmap to guide observational trait-based studies is also presented. Lastly, we highlight new areas where trait-based studies on terrestrial arthropods are well positioned to advance ecological understanding and application. These include examining the roles of competitive, non-competitive and (multi-)trophic interactions in shaping coexistence, and macro-scaling trait-environment relationships to explain and predict patterns in biodiversity and ecosystem functions across space and time. We hope this review will spur and guide future applications of the trait-based framework to advance ecological insights from the most diverse eukaryotic organisms on Earth.}, } @article {pmid30548379, year = {2018}, author = {Bogin, B}, title = {Frontiers of human biology-Bridging scientific and political boundaries.}, journal = {Evolutionary anthropology}, volume = {}, number = {}, pages = {}, doi = {10.1002/evan.21755}, pmid = {30548379}, issn = {1520-6505}, } @article {pmid30548192, year = {2018}, author = {Jin, Y and Liu, Y and Zhao, L and Zhao, F and Feng, J and Li, S and Chen, H and Sun, J and Zhu, B and Geng, R and Wei, Y}, title = {Gut microbiota in patients after surgical treatment for colorectal cancer.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14498}, pmid = {30548192}, issn = {1462-2920}, support = {81672351//National Natural Science Foundation of China/ ; 1252HQ017//the department of Education of Heilongjiang Province/ ; 2012LX001//the First Affiliated Hospital of Harbin Medical University/ ; }, abstract = {Colorectal cancer (CRC) is a common disease worldwide that is strongly associated with the gut microbiota. However, little is known regarding the gut microbiota after surgical treatment. 16S rRNA gene sequencing was used to evaluate differences in gut microbiota among colorectal adenoma patients, CRC patients, CRC postoperative patients and healthy controls by comparing gut microbiota diversity, overall composition and taxonomic signature abundance. The gut microbiota of CRC patients, adenoma patients and healthy controls developed in accordance with the adenoma-carcinoma sequence, with impressive shifts in the gut microbiota before or during the development of CRC. The gut microbiota of postoperative patients and CRC patients differed significantly. Subdividing CRC postoperative patients according to the presence or absence of newly developed adenoma which based on the colonoscopy findings revealed that the gut microbiota of newly developed adenoma patients differed significantly from that of clean intestine patients and was more similar to the gut microbiota of carcinoma patients than to the gut microbiota of healthy controls. The alterations of the gut microbiota between the two groups of postoperative patients corresponded to CRC prognosis. More importantly, we used the different gut microbiota as biomarkers to distinguish postoperative patients with or without newly developed adenoma, achieving an AUC value of 0.72. These insights on the changes in the gut microbiota of CRC patients after surgical treatment may allow the use of the microbiota as non-invasive biomarkers for the diagnosis of newly developed adenomas and to help prevent cancer recurrence in postoperative patients.}, } @article {pmid30548180, year = {2018}, author = {}, title = {Erratum.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {6-7}, pages = {390}, doi = {10.1002/jez.b.22832}, pmid = {30548180}, issn = {1552-5015}, } @article {pmid30548167, year = {2019}, author = {Barras, F}, title = {Art and microbiology: encounters of the third type.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {29-34}, doi = {10.1111/1758-2229.12717}, pmid = {30548167}, issn = {1758-2229}, support = {//Institut Pasteur/ ; //ANR/ ; //CNRS/ ; }, } @article {pmid30548156, year = {2018}, author = {Filker, S and Kühner, S and Heckwolf, M and Dierking, J and Stoeck, T}, title = {A fundamental difference between macrobiota and microbial eukaryotes: protistan plankton has a species maximum in the freshwater-marine transition zone of the Baltic Sea.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14502}, pmid = {30548156}, issn = {1462-2920}, support = {03F0682//EU & German BMBF/ ; //TU Nachwuchsring/ ; }, abstract = {Remane's Artenminimum at the horohalinicum is a fundamental concept in ecology to describe and explain the distribution of organisms along salinity gradients. However, a recent metadata analysis challenged this concept for protists, proposing a species maximum in brackish waters. Due to data bias, this literature-based investigation was highly discussed. Reliable data verifying or rejecting the species minimum for protists in brackish waters were critically lacking. Here, we sampled a pronounced salinity gradient along a west-east transect in the Baltic Sea and analysed protistan plankton communities using high-throughput eDNA metabarcoding. A strong salinity barrier at the upper limit of the horohalinicum and 10 psu appeared to select for significant shifts in protistan community structures, with dinoflagellates being dominant at lower salinities, and dictyochophytes and diatoms being keyplayers at higher salinities. Also in vertical water column gradients in deeper basins (Kiel Bight, Arkona and Bornholm Basin) appeared salinity as significant environmental determinant influencing alpha- and beta-diversity patterns. Importantly, alpha-diversity indices revealed species maxima in brackish waters, that is, indeed contrasting Remane's Artenminimum concept. Statistical analyses confirmed salinity as the major driving force for protistan community structuring with high significance. This suggests that macrobiota and microbial eukaryotes follow fundamentally different rules regarding diversity patterns in the transition zone from freshwater to marine waters.}, } @article {pmid30548120, year = {2018}, author = {Abin, CA and Hollibaugh, JT}, title = {Transcriptional response of the obligate anaerobe Desulfuribacillus stibiiarsenatis MLFW-2T to growth on antimonate and other terminal electron acceptors.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14503}, pmid = {30548120}, issn = {1462-2920}, support = {//Alfred P. Sloan Foundation/ ; EAR 09-52271//National Science Foundation/ ; DGE-0903734//National Science Foundation/ ; }, abstract = {Enzymes of the dimethyl sulfoxide reductase (DMSOR) family catalyse two-electron redox reactions pivotal to the dissimilatory metabolism of a variety of organic and inorganic compounds. The draft genome of the obligately anaerobic bacterium Desulfuribacillus stibiiarsenatis MLFW-2T contains 14 genes that are predicted to encode catalytic subunits of DMSOR family enzymes. We quantified transcription of these genes during growth on antimonate, arsenate, nitrate and selenate, with the goal of identifying the respiratory antimonate reductase. Transcription of BHU72_10330, BHU72_03635 and BHU72_07355 was enhanced during growth on arsenate, nitrate and selenate, respectively, implicating these genes as encoding the catalytic subunits of a respiratory arsenate reductase (arrA), periplasmic nitrate reductase (napA) and membrane-bound selenate reductase (srdA) respectively. Transcription of BHU72_07145 increased markedly when MLFW-2T was grown on antimonate, suggesting that this gene encodes the catalytic subunit of a respiratory antimonate reductase, designated anrA. We also compared the transcriptomes of MLFW-2T during growth on antimonate and arsenate to examine the broader physiological response of the organism to growth on these substrates. Relative to arsenate, antimonate was found to induce transcription of genes involved in pathways for dealing with oxidative stress, including those involved in repairing damaged cellular biomolecules and scavenging reactive oxygen species.}, } @article {pmid30548107, year = {2018}, author = {Beier, S and Holtermann, PL and Numberger, D and Schott, T and Umlauf, L and Jürgens, K}, title = {A metatranscriptomics-based assessment of small-scale mixing of sulfidic and oxic waters on redoxcline prokaryotic communities.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14499}, pmid = {30548107}, issn = {1462-2920}, support = {JU367/16-1//Deutsche Forschungsgemeinschaft/ ; UM79/5-1//Deutsche Forschungsgemeinschaft/ ; 03F0679A//Seventh Framework Programme/ ; }, abstract = {Lateral intrusions of oxygen caused by small-scale mixing are thought to shape microbial activity in marine redoxclines. To examine the response of prokaryotes to such mixing events we employed a shipboard mixing experiment in the euxinic central Baltic Sea: oxic, nitrate containing and sulfidic water samples without detectable oxygenized substances were incubated directly or after mixing. While nitrate, nitrite and ammonium concentrations stayed approximately constant in all incubations, we observed a decrease of sulfide after the contact with oxygen in the sulfide containing incubations. The transcription of marker genes from chemolithoauthotrophic key players including archaeal nitrifiers as well as gammaproteobacterial and campylobacterial autotrophic organisms that couple denitrification with sulfur-oxidation were followed at four time points within 8.5 h. The temporally contrasting transcriptional profiles of gammaproteobacterial and campylobacterial denitrifiers that depend on the same inorganic substrates pointed to a niche separation. Particular archaeal and campylobacterial marker genes involved in nitrification, denitrification and sulfur oxidation, which depend on oxidized substrates, were highly upregulated in the anaerobic sulfidic samples. We suggest that, despite the absence of measurable oxygenated compounds in the sulfidic water, frequent intermittent small-scale intrusions stimulate the permanent upregulation of genes involved in nitrification, denitrification and sulfur oxidation.}, } @article {pmid30547859, year = {2018}, author = {Wu, S and Xia, X and Zhou, Z and Wang, D and Wang, G}, title = {Nocardioides gansuensis sp. nov., isolated from geopark soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003157}, pmid = {30547859}, issn = {1466-5034}, abstract = {A novel bacterial strain, designated WSJ-1T, was isolated from geopark soil in Gansu province, PR China. The highest 16S rRNA gene sequence similarities were to those of Nocardioides sediminis MSL-01T (97.10 %), Nocardioides aquiterrae GW-9T (97.08 %) and Nocardioides terrigena DS-17T (96.94 %). Strain WSJ-1T grouped with N. terrigena DS-17T and N. sediminis MSL-01T in 16S rRNA gene-based phylogenetic trees. The DNA-DNA relatedness of WSJ-1T/N. sediminis JCM19559T and WSJ-1T/N. aquiterrae JCM11813T were 44.8 and 29.2 %, respectively. Average nucleotide identity values of whole genome sequences of WSJ-1T/N. terrigena KCTC19217T and WSJ-1T/N. sediminis KCTC19271T were 78.83 and 78.83 %, respectively. Its genome size was 4.76 Mb, comprising 4517 predicted genes with a DNA G+C content of 70.9 %. Strain WSJ-1T contained menaquinone-8(H4) as the major respiratory quinone and ll-2,6-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol. The major cellular fatty acids were iso-C16 : 0, C18 : 1ω9c and C17 : 1ω8c. Based on the polyphasic analyses, the isolate is considered to represent a novel species of the genus Nocardioides, for which the name Nocardioidesgansuensis sp. nov. is proposed. The type strain is WSJ-1T (=KCTC 49117T=CCTCC AB 2018027T).}, } @article {pmid30547854, year = {2018}, author = {Zhu, ZN and Li, YR and Li, YQ and Xiao, M and Han, MX and Wadaan, MAM and Hozzein, WN and An, DD and Li, WJ}, title = {Microbacterium suaedae sp. nov., isolated from Suaeda aralocaspica.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003162}, pmid = {30547854}, issn = {1466-5034}, abstract = {Two bacterial strains, YZYP 306T and YZGP 509, were isolated from the halophyte Suaeda aralocaspica collected from the southern edge of the Gurbantunggut desert, north-west China. Cells were Gram-stain-positive, aerobic, non-motile, short rods. Strain YZYP 306T grew at 4-40 °C, while strain YZGP 509 grew at 4-42 °C, with optimum growth at 28 °C, and they both grew at pH 6.0-12.0 and 0-15 % (w/v) NaCl. Phylogenetic analyses of the 16S rRNA gene sequences placed the two strains within the genus Microbacterium with the highest similarities to Microbacterium indicum BBH6T (97.8 %) and Microbacterium sorbitolivorans SZDIS-1-1T (97.2 %). The average nucleotide identity value between YZYP 306T and M. indicum BBH6T was 78.3 %. The genomic DNA G+C contents of strains YZYP 306T and YZGP 509 were 68.49 and 68.53 mol%, respectively. The characteristic cell-wall amino acid was ornithine. Whole-cell sugars were galactose, mannose and ribose. The acyl type of the peptidoglycan was glycolyl. The major cellular fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The major menaquinones were MK-10 and MK-11. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. These results are consistent with the classification of the two strains into the genus Microbacterium. On the basis of the evidence presented in this study, strains YZYP 306T and YZGP 509 are representatives of a novel species in the genus Microbacterium, for which the name Microbacterium suaedae sp. nov. is proposed. The type strain is YZYP 306T (=CGMCC 1.16261T=KCTC 49101T).}, } @article {pmid30547851, year = {2018}, author = {Hwang, S and Tatum, T and Lebepe-Mazur, S and Nicholson, EM}, title = {Preparation of lyophilized recombinant prion protein for TSE diagnosis by RT-QuIC.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {895}, doi = {10.1186/s13104-018-3982-5}, pmid = {30547851}, issn = {1756-0500}, abstract = {OBJECTIVE: Transmissible spongiform encephalopathies (TSEs) are a group of fatal neurodegenerative diseases, often referred as prion diseases. TSEs result from the misfolding of the cellular prion protein (PrPC) into a pathogenic form (PrPSc) that accumulates in the brain and lymphatic tissue. Amplification based assays such as real-time quaking induced conversion allow us to assess the conversion of PrPC to PrPSc. Real-time quaking induced conversion (RT-QuIC) can be used for the detection of PrPSc in a variety of biological tissues from humans and animals. However, RT-QuIC requires a continuous supply of freshly purified prion protein and this necessity is not sustainable in a diagnostic laboratory setting.

RESULTS: In this study, we developed a method to dry and preserve the prion protein for long term storage allowing for production of the protein and storage for extended time prior to use and room temperature shipping to appropriate diagnostic laboratory destinations facilitating widespread use of RT-QuIC as a diagnostic method.}, } @article {pmid30547848, year = {2018}, author = {Mbanga, C and Makebe, H and Tim, D and Fonkou, S and Toukam, L and Njim, T}, title = {Determinants of burnout syndrome among nurses in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {893}, doi = {10.1186/s13104-018-4004-3}, pmid = {30547848}, issn = {1756-0500}, abstract = {OBJECTIVES: Burnout syndrome is common amongst medical personnel. The objective of this study was to identify determinants of burnout syndrome among nurses in the north west and south west regions of Cameroon.

RESULTS: A cross-sectional analysis during the months of January-June 2018 was carried out recruiting nurses consecutively after consent from state-owned and private hospitals in the English-speaking regions of Cameroon. Burnout was assessed using the Oldenburg Burnout Inventory (OLBI). Univariable regression analysis used to identify determinants of burnout syndrome among 143 nurses (mean age 29.75 ± 6.55 years) showed that being in a personal relationship (Beta = 2.25) significantly explained 3.8% of the variation in burnout (R2 = 3.8, F (1, 125) = 4.89, p = 0.029).}, } @article {pmid30547846, year = {2018}, author = {Kelly, GE}, title = {A neural network analysis of Lifeways cross-generation imputed data.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {897}, doi = {10.1186/s13104-018-4013-2}, pmid = {30547846}, issn = {1756-0500}, abstract = {OBJECTIVES: Neural networks are a powerful statistical tool that use nonlinear regression type models to obtain predictions. Their use in the Lifeways cross-generation study that examined body mass index (BMI) of children, among other measures, is explored here. Our aim is to predict the BMI of children from that of their parents and maternal and paternal grandparents. For comparison purposes, linear models will also be used for prediction. A complicating factor is the large amount of missing data. The missing data may be imputed and we examine the effects of different imputation methods on prediction. An analysis using neural networks (and also linear models) that uses all available data without imputation is also carried out, and is the gold standard by which the analyses with imputed data sets are compared.

RESULTS: Neural network models performed better than linear models and can be used as a data analytic tool to detect nonlinear and interaction effects. Using neural networks the BMI of a child can be predicted from family members to within roughly 2.84 units. Results between the imputation methods were similar in terms of mean squared error, as were results based on imputed data compared to un-imputed data.}, } @article {pmid30547845, year = {2018}, author = {Cogill, SB and Srivastava, AK and Yang, MQ and Wang, L}, title = {Co-expression of long non-coding RNAs and autism risk genes in the developing human brain.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {91}, doi = {10.1186/s12918-018-0639-x}, pmid = {30547845}, issn = {1752-0509}, support = {P20 GM103429/GM/NIGMS NIH HHS/United States ; R15 GM114739/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Autism Spectrum Disorder (ASD) is the umbrella term for a group of neurodevelopmental disorders convergent on behavioral phenotypes. While many genes have been implicated in the disorder, the predominant focus of previous research has been on protein coding genes. This leaves a vast number of long non-coding RNAs (lncRNAs) not characterized for their role in the disorder although lncRNAs have been shown to play important roles in development and are highly represented in the brain. Studies have also shown lncRNAs to be differentially expressed in ASD affected brains. However, there has yet to be an enrichment analysis of the shared ontologies and pathways of known ASD genes and lncRNAs in normal brain development.

RESULTS: In this study, we performed co-expression network analysis on the developing brain transcriptome to identify potential lncRNAs associated with ASD and possible annotations for functional role of lncRNAs in brain development. We found co-enrichment of lncRNA genes and ASD risk genes in two distinct groups of modules showing elevated prenatal and postnatal expression patterns, respectively. Further enrichment analysis of the module groups indicated that the early expression modules were comprised mainly of transcriptional regulators while the later expression modules were associated with synapse formation. Finally, lncRNAs were prioritized for their connectivity with the known ASD risk genes through analysis of an adjacency matrix. Collectively, the results imply early developmental repression of synaptic genes through lncRNAs and ASD transcriptional regulators.

CONCLUSION: Here we demonstrate the utility of mining the publically available brain gene expression data to further functionally annotate the role of lncRNAs in ASD. Our analysis indicates that lncRNAs potentially have a key role in ASD due to their convergence on shared pathways, and we identify lncRNAs of interest that may lead to further avenues of study.}, } @article {pmid30547841, year = {2018}, author = {Admasu, E and Mekonnen, A and Setegn, T and Abeje, G}, title = {Level of unintended pregnancy among reproductive age women in Bahir Dar city administration, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {891}, doi = {10.1186/s13104-018-4016-z}, pmid = {30547841}, issn = {1756-0500}, abstract = {OBJECTIVE: The objective of this study was to determine the prevalence and determinants of unintended pregnancy among reproductive age women in Bahir Dar town, Northwest Ethiopia.

RESULT: The prevalence of unintended pregnancy was 15.8% (95% CI 13.8%-17.7%). Single women (AOR 0.18; 95% CI 0.08-0.40), women living away from their husband (AOR 4.18; 95% CI 2.64-6.61) and women with no access/exposure to mass-media (AOR 1.89; 95% CI 1.13-3.15) were more likely to have unintended pregnancy compared to their counter parts.}, } @article {pmid30547839, year = {2018}, author = {Boke, MM and Geremew, AB}, title = {Low dietary diversity and associated factors among lactating mothers in Angecha districts, Southern Ethiopia: community based cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {892}, doi = {10.1186/s13104-018-4001-6}, pmid = {30547839}, issn = {1756-0500}, abstract = {OBJECTIVE: The objective of the study was to assess prevalence low dietary diversity and associated factors among lactating mother in Angecha district, Southern Ethiopia.

RESULTS: The magnitude of low dietary diversity was 52.2%, 95% confidence interval (47.4, 57.27). From multivariable logistic analysis mothers were illiterate had 2.5 times more likely to have low dietary diversity than had formal education. Mothers living in the rural area were 3.1 times more likely to have low dietary diversity as compared with living urban area and women who have Household food insecure was 3.4 times more likely to have low dietary diversity as compared to a counterpart. Therefore, health provider could provide nutritional education focusing illiterate and rural women.}, } @article {pmid30547838, year = {2018}, author = {Senanayake, HM and Patabendige, M and Ramachandran, R}, title = {Piloting of WHO Safe Childbirth Checklist using a modified version in Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {896}, doi = {10.1186/s13104-018-4009-y}, pmid = {30547838}, issn = {1756-0500}, abstract = {OBJECTIVES: Data was gathered to study the impact of a context-specific modified WHO Safe Childbirth Checklist (mSCC) at two tertiary care settings in Sri Lanka, as a part of an implementation program.

DATA DESCRIPTION: We provide data sets of a prospective observational study which was conducted in the University Obstetrics Unit at De Soysa Hospital for Women (DSHW), Colombo and two Obstetric Units at Teaching Hospital, Mahamodara, Galle (THMG), Sri Lanka. These consist of demographic and checklist implementation details and data on the level of acceptance. The study was conducted over 8 weeks at DSHW and over 4 weeks at THMG. Checklists were kept attached to clinical records at admission and collected on discharge. Level of acceptance was assessed using a self-administered questionnaire. Outcome measures were adoption rate (percentage of deliveries where mSCC was used), adherence to practices (mean percentage of items checked in each checklist), response rate (percentage of staff members who responded to questionnaire) and level of acceptance (percentage of "strongly agree/agree" in Likert scale to five questions regarding acceptance of modified SCC).}, } @article {pmid30547832, year = {2018}, author = {Tellier, M and Hardy, JG and Norbury, CJ and Murphy, S}, title = {Effect of CFIm25 knockout on RNA polymerase II transcription.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {894}, doi = {10.1186/s13104-018-4006-1}, pmid = {30547832}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; WT106134AIA//Wellcome Trust/United Kingdom ; C38302/A13012//Cancer Research UK/United Kingdom ; }, abstract = {OBJECTIVES: Transcription of eukaryotic protein-coding genes by RNA polymerase II (pol II) is a highly regulated process. Most human genes have multiple poly(A) sites, which define different possible mRNA ends, suggesting the existence of mechanisms that regulate which poly(A) site is used. Poly(A) site selection may be mediated by cleavage factor I (CFIm), which is part of the cleavage and polyadenylation (CPA) complex. CFIm comprises CFIm25, CFIm59 and CFim68 subunits. It has been documented that the CPA complex also regulates pol II transcription at the start of genes. We therefore investigated whether CFIm, in addition to its role in poly(A) site selection, is involved in the regulation of pol II transcription.

DATA DESCRIPTION: We provide genome-wide data of the effect of reducing by 90% expression of the CFIm25 constituent of CFIm, which is involved in pre-mRNA cleavage and polyadenylation, on pol II transcription in human cells. We performed pol II ChIP-seq in the presence or absence of CFIm25 and with or without an inhibitor of the cyclin-dependent kinase (CDK)9, which regulates the entry of pol II into productive elongation.}, } @article {pmid30547817, year = {2018}, author = {Li, D and Yang, W and Arthur, C and Liu, JS and Cruz-Niera, C and Yang, MQ}, title = {Systems biology analysis reveals new insights into invasive lung cancer.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {117}, doi = {10.1186/s12918-018-0637-z}, pmid = {30547817}, issn = {1752-0509}, support = {R15 GM114739/GM/NIGMS NIH HHS/United States ; R25 DK101408/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Adenocarcinoma in situ (AIS) is a pre-invasive lesion in the lung and a subtype of lung adenocarcinoma. The patients with AIS can be cured by resecting the lesion completely. In contrast, the patients with invasive lung adenocarcinoma have very poor 5-year survival rate. AIS can develop into invasive lung adenocarcinoma. The investigation and comparison of AIS and invasive lung adenocarcinoma at the genomic level can deepen our understanding of the mechanisms underlying lung cancer development.

RESULTS: In this study, we identified 61 lung adenocarcinoma (LUAD) invasive-specific differentially expressed genes, including nine long non-coding RNAs (lncRNAs) based on RNA sequencing techniques (RNA-seq) data from normal, AIS, and invasive tissue samples. These genes displayed concordant differential expression (DE) patterns in the independent stage III LUAD tissues obtained from The Cancer Genome Atlas (TCGA) RNA-seq dataset. For individual invasive-specific genes, we constructed subnetworks using the Genetic Algorithm (GA) based on protein-protein interactions, protein-DNA interactions and lncRNA regulations. A total of 19 core subnetworks that consisted of invasive-specific genes and at least one putative lung cancer driver gene were identified by our study. Functional analysis of the core subnetworks revealed their enrichment in known pathways and biological progresses responsible for tumor growth and invasion, including the VEGF signaling pathway and the negative regulation of cell growth.

CONCLUSIONS: Our comparison analysis of invasive cases, normal and AIS uncovered critical genes that involved in the LUAD invasion progression. Furthermore, the GA-based network method revealed gene clusters that may function in the pathways contributing to tumor invasion. The interactions between differentially expressed genes and putative driver genes identified through the network analysis can offer new targets for preventing the cancer invasion and potentially increase the survival rate for cancer patients.}, } @article {pmid30547805, year = {2018}, author = {He, G and Liang, Y and Chen, Y and Yang, W and Liu, JS and Yang, MQ and Guan, R}, title = {A hotspots analysis-relation discovery representation model for revealing diabetes mellitus and obesity.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {116}, doi = {10.1186/s12918-018-0640-4}, pmid = {30547805}, issn = {1752-0509}, support = {R15 GM114739/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Nowadays, because of the huge economic burden on society causing by obesity and diabetes, they turn into the most serious public health challenges in the world. To reveal the close and complex relationships between diabetes, obesity and other diseases, search the effective treatment for them, a novel model named as representative latent Dirichlet allocation (RLDA) topic model is presented.

RESULTS: RLDA was applied to a corpus of more than 337,000 literatures of diabetes and obesity which were published from 2007 to 2016. To unveil those meaningful relationships between diabetes mellitus, obesity and other diseases, we performed an explicit analysis on the output of our model with a series of visualization tools. Then, with the clinical reports which were not used in the training data to show the credibility of our discoveries, we find that a sufficient number of these records are matched directly. Our results illustrate that in the last 10 years, for obesity accompanying diseases, scientists and researchers mainly focus on 17 of them, such as asthma, gastric disease, heart disease and so on; for the study of diabetes mellitus, it features a more broad scope of 26 diseases, such as Alzheimer's disease, heart disease and so forth; for both of them, there are 15 accompanying diseases, listed as following: adrenal disease, anxiety, cardiovascular disease, depression, heart disease, hepatitis, hypertension, hypothalamic disease, respiratory disease, myocardial infarction, OSAS, liver disease, lung disease, schizophrenia, tuberculosis. In addition, tumor necrosis factor, tumor, adolescent obesity or diabetes, inflammation, hypertension and cell are going be the hot topics related to diabetes mellitus and obesity in the next few years.

CONCLUSIONS: With the help of RLDA, the hotspots analysis-relation discovery results on diabetes and obesity were achieved. We extracted the significant relationships between them and other diseases such as Alzheimer's disease, heart disease and tumor. It is believed that the new proposed representation learning algorithm can help biomedical researchers better focus their attention and optimize their research direction.}, } @article {pmid30547801, year = {2018}, author = {Gong, P and Donohue, KB and Mayo, AM and Wang, Y and Hong, H and Wilbanks, MS and Barker, ND and Guan, X and Gust, KA}, title = {Comparative toxicogenomics of three insensitive munitions constituents 2,4-dinitroanisole, nitroguanidine and nitrotriazolone in the soil nematode Caenorhabditis elegans.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {92}, doi = {10.1186/s12918-018-0636-0}, pmid = {30547801}, issn = {1752-0509}, support = {P40 OD010440/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: Ecotoxicological studies on the insensitive munitions formulation IMX-101 and its components 2,4-dinitroanisole (DNAN), nitroguanidine (NQ) and nitrotriazolone (NTO) in various organisms showed that DNAN was the main contributor to the overall toxicity of IMX-101 and suggested that the three compounds acted independently. These results motivated this toxicogenomics study to discern toxicological mechanisms for these compounds at the molecular level.

METHODS: Here we used the soil nematode Caenorhabditis elegans, a well-characterized genomics model, as the test organism and a species-specific, transcriptome-wide 44 K-oligo probe microarray for gene expression analysis. In addition to the control treatment, C. elegans were exposed for 24 h to 6 concentrations of DNAN (1.95-62.5 ppm) or NQ (83-2667 ppm) or 5 concentrations of NTO (187-3000 ppm) with ten replicates per treatment. The nematodes were transferred to a clean environment after exposure. Reproduction endpoints (egg and larvae counts) were measured at three time points (i.e., 24-, 48- and 72-h). Gene expression profiling was performed immediately after 24-h exposure to each chemical at the lowest, medium and highest concentrations plus the control with four replicates per treatment.

RESULTS: Statistical analyses indicated that chemical treatment did not significantly affect nematode reproduction but did induce 2175, 378, and 118 differentially expressed genes (DEGs) in NQ-, DNAN-, and NTO-treated nematodes, respectively. Bioinformatic analysis indicated that the three compounds shared both DEGs and DEG-mapped Reactome pathways. Gene set enrichment analysis further demonstrated that DNAN and NTO significantly altered 12 and 6 KEGG pathways, separately, with three pathways in common. NTO mainly affected carbohydrate, amino acid and xenobiotics metabolism while DNAN disrupted protein processing, ABC transporters and several signal transduction pathways. NQ-induced DEGs were mapped to a wide variety of metabolism, cell cycle, immune system and extracellular matrix organization pathways.

CONCLUSION: Despite the absence of significant effects on apical reproduction endpoints, DNAN, NTO and NQ caused significant alterations in gene expression and pathways at 1.95 ppm, 187 ppm and 83 ppm, respectively. This study provided supporting evidence that the three chemicals may exert independent toxicity by acting on distinct molecular targets and pathways.}, } @article {pmid30547798, year = {2018}, author = {Yang, MQ and Weissman, SM and Yang, W and Zhang, J and Canaann, A and Guan, R}, title = {MISC: missing imputation for single-cell RNA sequencing data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {114}, doi = {10.1186/s12918-018-0638-y}, pmid = {30547798}, issn = {1752-0509}, support = {R15 GM114739/GM/NIGMS NIH HHS/United States ; R25 DK101408/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Single-cell RNA sequencing (scRNA-seq) technology provides an effective way to study cell heterogeneity. However, due to the low capture efficiency and stochastic gene expression, scRNA-seq data often contains a high percentage of missing values. It has been showed that the missing rate can reach approximately 30% even after noise reduction. To accurately recover missing values in scRNA-seq data, we need to know where the missing data is; how much data is missing; and what are the values of these data.

METHODS: To solve these three problems, we propose a novel model with a hybrid machine learning method, namely, missing imputation for single-cell RNA-seq (MISC). To solve the first problem, we transformed it to a binary classification problem on the RNA-seq expression matrix. Then, for the second problem, we searched for the intersection of the classification results, zero-inflated model and false negative model results. Finally, we used the regression model to recover the data in the missing elements.

RESULTS: We compared the raw data without imputation, the mean-smooth neighbor cell trajectory, MISC on chronic myeloid leukemia data (CML), the primary somatosensory cortex and the hippocampal CA1 region of mouse brain cells. On the CML data, MISC discovered a trajectory branch from the CP-CML to the BC-CML, which provides direct evidence of evolution from CP to BC stem cells. On the mouse brain data, MISC clearly divides the pyramidal CA1 into different branches, and it is direct evidence of pyramidal CA1 in the subpopulations. In the meantime, with MISC, the oligodendrocyte cells became an independent group with an apparent boundary.

CONCLUSIONS: Our results showed that the MISC model improved the cell type classification and could be instrumental to study cellular heterogeneity. Overall, MISC is a robust missing data imputation model for single-cell RNA-seq data.}, } @article {pmid30547796, year = {2018}, author = {Yang, B and Xu, Y and Maxwell, A and Koh, W and Gong, P and Zhang, C}, title = {MICRAT: a novel algorithm for inferring gene regulatory networks using time series gene expression data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {115}, doi = {10.1186/s12918-018-0635-1}, pmid = {30547796}, issn = {1752-0509}, abstract = {BACKGROUND: Reconstruction of gene regulatory networks (GRNs), also known as reverse engineering of GRNs, aims to infer the potential regulation relationships between genes. With the development of biotechnology, such as gene chip microarray and RNA-sequencing, the high-throughput data generated provide us with more opportunities to infer the gene-gene interaction relationships using gene expression data and hence understand the underlying mechanism of biological processes. Gene regulatory networks are known to exhibit a multiplicity of interaction mechanisms which include functional and non-functional, and linear and non-linear relationships. Meanwhile, the regulatory interactions between genes and gene products are not spontaneous since various processes involved in producing fully functional and measurable concentrations of transcriptional factors/proteins lead to a delay in gene regulation. Many different approaches for reconstructing GRNs have been proposed, but the existing GRN inference approaches such as probabilistic Boolean networks and dynamic Bayesian networks have various limitations and relatively low accuracy. Inferring GRNs from time series microarray data or RNA-sequencing data remains a very challenging inverse problem due to its nonlinearity, high dimensionality, sparse and noisy data, and significant computational cost, which motivates us to develop more effective inference methods.

RESULTS: We developed a novel algorithm, MICRAT (Maximal Information coefficient with Conditional Relative Average entropy and Time-series mutual information), for inferring GRNs from time series gene expression data. Maximal information coefficient (MIC) is an effective measure of dependence for two-variable relationships. It captures a wide range of associations, both functional and non-functional, and thus has good performance on measuring the dependence between two genes. Our approach mainly includes two procedures. Firstly, it employs maximal information coefficient for constructing an undirected graph to represent the underlying relationships between genes. Secondly, it directs the edges in the undirected graph for inferring regulators and their targets. In this procedure, the conditional relative average entropies of each pair of nodes (or genes) are employed to indicate the directions of edges. Since the time delay might exist in the expression of regulators and target genes, time series mutual information is combined to cooperatively direct the edges for inferring the potential regulators and their targets. We evaluated the performance of MICRAT by applying it to synthetic datasets as well as real gene expression data and compare with other GRN inference methods. We inferred five 10-gene and five 100-gene networks from the DREAM4 challenge that were generated using the gene expression simulator GeneNetWeaver (GNW). MICRAT was also used to reconstruct GRNs on real gene expression data including part of the DNA-damaged response pathway (SOS DNA repair network) and experimental dataset in E. Coli. The results showed that MICRAT significantly improved the inference accuracy, compared to other inference methods, such as TDBN, etc. CONCLUSION: In this work, a novel algorithm, MICRAT, for inferring GRNs from time series gene expression data was proposed by taking into account dependence and time delay of expressions of a regulator and its target genes. This approach employed maximal information coefficients for reconstructing an undirected graph to represent the underlying relationships between genes. The edges were directed by combining conditional relative average entropy with time course mutual information of pairs of genes. The proposed algorithm was evaluated on the benchmark GRNs provided by the DREAM4 challenge and part of the real SOS DNA repair network in E. Coli. The experimental study showed that our approach was comparable to other methods on 10-gene datasets and outperformed other methods on 100-gene datasets in GRN inference from time series datasets.}, } @article {pmid30547787, year = {2018}, author = {Yohannes, E and Rothhaupt, KO}, title = {Dietary nutrient allocation to somatic tissue synthesis in emerging subimago freshwater mayfly Ephemera danica.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {57}, doi = {10.1186/s12898-018-0213-9}, pmid = {30547787}, issn = {1472-6785}, abstract = {BACKGROUND: The relative importance of nutrients derived from different sources for tissue synthesis is crucial for predicting a species responds to changes in food availability. The ecological and physiological strategies that govern the incorporation and routing of nutrients for reproduction are often well understood. However, the role and adaptive value of both species and individual variation during early life-stage remain elusive. In freshwater systems, dietary nutrient allocation to somatic tissue should be favoured when dietary source peaks and resource limitation may hinder flexible resource allocation. We used carbon and nitrogen stable isotopes (δ13C and δ15N) to examine metabolic nutrient routing and resource allocation from four dietary sources used to biosynthesize three somatic tissues of emerging subimago Ephemera danica. Aquatic emerging insects, such as the mayfly E. danica, are well suited for such studies. This is because, while burrowing nymph phase is a detritivores feeders with several early life-stages of metamorphosis, adult insects do not feed during this period but do utilize energy.

RESULTS: Constructed models to predict percent proportional contribution of source to tissue showed that terrestrial detritus was the dominant nutrient source for abdomen, head and wing with mean values of 57%, 65% and 73%, respectively. There was evidence for differential resource allocation, as insect partitioned periphyton and sediment (but also seston) elements for tissue synthesis. Utilizing individual-specimen based relationship in isotope value; we derived tissue specific isotopic niche estimates, for the different tissue-source combinations.

CONCLUSIONS: Results indicate that tissue selection is crucial for isotopic ecological measurements in arthropods. Mayfly has long been used as bio-indicator of freshwater ecosystems and their larvae show rapid response to environmental changes. In light of the recent evidence of drastic reduction in flying insect mass in Germany, developing a system using isotopic tools to trace nutrient flow in this important taxon will assist conservation and management efforts.}, } @article {pmid30547784, year = {2018}, author = {Guo, M and Lu, S and Huang, H and Wang, Y and Yang, MQ and Yang, Y and Fan, Z and Jiang, B and Deng, Y}, title = {Increased AURKA promotes cell proliferation and predicts poor prognosis in bladder cancer.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {118}, doi = {10.1186/s12918-018-0634-2}, pmid = {30547784}, issn = {1752-0509}, support = {P20 GM103466/GM/NIGMS NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; }, abstract = {BACKGROUND: Bladder cancer (BC) is the most common cancer of the urinary bladder and upper tract, in which the clinical management is limited. AURKA (aurora kinase A) has been identified as an oncogene in cancer development; however, its potential role and underlying mechanisms in the progression of BC remain unknown.

RESULTS: In this study, we evaluated Aurora kinase A (AURKA) expression in patient samples by performing gene expression profiling, and found that AURKA expression levels were significantly higher in BC tissues than in normal tissues. Increased AURKA in BC was strongly associated with stage and grade. Moreover, BC patients with elevated AURKA achieved poor overall survival rates. The experiments in vitro comprehensively validated the critical role of AURKA in promoting BC cell proliferation using the methods of gene overexpression and gene silencing. Furthermore, we proved that AURKA inhibitor MLN8237 arrested BC cell growth and induced apoptosis.

CONCLUSIONS: These findings implicate AURKA acting as an effective biomarker for BC detection and prognosis, as well as therapeutic target.}, } @article {pmid30547775, year = {2018}, author = {Hu, L and Zhang, R and Yuan, Q and Gao, Y and Yang, MQ and Zhang, C and Huang, J and Sun, Y and Yang, W and Yang, JY and Min, ZL and Cheng, J and Deng, Y and Hu, X}, title = {The emerging role of microRNA-4487/6845-3p in Alzheimer's disease pathologies is induced by Aβ25-35 triggered in SH-SY5Y cell.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 7}, pages = {119}, doi = {10.1186/s12918-018-0633-3}, pmid = {30547775}, issn = {1752-0509}, support = {P20 GM103466/GM/NIGMS NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; U54 MD007584/MD/NIMHD NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; }, abstract = {BACKGROUND: Accumulation of amyloid β-peptide (Aβ) is implicated in the pathogenesis and development of Alzheimer's disease (AD). Neuron-enriched miRNA was aberrantly regulated and may be associated with the pathogenesis of AD. However, regarding whether miRNA is involved in the accumulation of Aβ in AD, the underlying molecule mechanism remains unclear. Therefore, we conduct a systematic identification of the promising role of miRNAs in Aβ deposition, and shed light on the molecular mechanism of target miRNAs underlying SH-SY5Y cells treated with Aβ-induced cytotoxicity.

RESULTS: Statistical analyses of microarray data revealed that 155 significantly upregulated and 50 significantly downregulated miRNAs were found on the basis of log2 | Fold Change | ≥ 0.585 and P < 0.05 filter condition through 2588 kinds of mature miRNA probe examined. PCR results show that the expression change trend of the selected six miRNAs (miR-6845-3p, miR-4487, miR-4534, miR-3622-3p, miR-1233-3p, miR-6760-5p) was consistent with the results of the gene chip. Notably, Aβ25-35 downregulated hsa-miR-4487 and upregulated hsa-miR-6845-3p in SH-SY5Y cell lines associated with Aβ-mediated pathophysiology. Increase of hsa-miR-4487 could inhibit cells apoptosis, and diminution of hsa-miR-6845-3p could attenuate axon damage mediated by Aβ25-35 in SH-SY5Y.

CONCLUSIONS: Together, these findings suggest that dysregulation of hsa-miR-4487 and hsa-miR-6845-3p contributed to the pathogenesis of AD associated with Aβ25-35 mediated by triggering cell apoptosis and synaptic dysfunction. It might be beneficial to understand the pathogenesis and development of clinical diagnosis and treatment of AD. Further, our well-designed validation studies will test the miRNAs signature as a prognostication tool associated with clinical outcomes in AD.}, } @article {pmid30547764, year = {2018}, author = {Roy, A and Palli, SR}, title = {Epigenetic modifications acetylation and deacetylation play important roles in juvenile hormone action.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {934}, doi = {10.1186/s12864-018-5323-4}, pmid = {30547764}, issn = {1471-2164}, support = {R01 GM070559/GM/NIGMS NIH HHS/United States ; GM070559-11//National Institute of General Medical Sciences/ ; 2351177000//Agricultural Research Service/ ; }, abstract = {BACKGROUND: Epigenetic modifications including DNA methylation and post-translational modifications of histones are known to regulate gene expression. Antagonistic activities of histone acetyltransferases (HATs) and histone deacetylases (HDACs) mediate transcriptional reprogramming during insect development as shown in Drosophila melanogaster and other insects. Juvenile hormones (JH) play vital roles in the regulation of growth, development, metamorphosis, reproduction and other physiological processes. However, our current understanding of epigenetic regulation of JH action is still limited. Hence, we studied the role of CREB binding protein (CBP, contains HAT domain) and Trichostatin A (TSA, HDAC inhibitor) on JH action.

RESULTS: Exposure of Tribolium castaneum cells (TcA cells) to JH or TSA caused an increase in expression of Kr-h1 (a known JH-response gene) and 31 or 698 other genes respectively. Knockdown of the gene coding for CBP caused a decrease in the expression of 456 genes including Kr-h1. Interestingly, the expression of several genes coding for transcription factors, nuclear receptors, P450 and fatty acid synthase family members that are known to mediate JH action were affected by CBP knockdown or TSA treatment.

CONCLUSIONS: These data suggest that acetylation and deacetylation mediated by HATs and HDACs play an important role in JH action.}, } @article {pmid30547762, year = {2018}, author = {Wang, L and Xu, X and Yang, J and Chen, L and Liu, B and Liu, T and Jin, Q}, title = {Integrated microRNA and mRNA analysis in the pathogenic filamentous fungus Trichophyton rubrum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {933}, doi = {10.1186/s12864-018-5316-3}, pmid = {30547762}, issn = {1471-2164}, support = {2016-I2M-3-021//CAMS Innovation Fund for Medical Sciences (CIFMS)/ ; }, abstract = {BACKGROUND: Trichophyton rubrum (T. rubrum) is an important model organism of dermatophytes, which are the most common fungal pathogens worldwide. Despite the severity and prevalence of the infection caused by these pathogens, current therapies are not sufficient. MicroRNA (miRNA) is a class of small noncoding RNAs that are key factors in the regulation of gene expression. These miRNAs are reported to be highly conserved in different organisms and are involved in various essential cellular processes. In this study, we performed an integrated analysis of microRNA-like RNAs (milRNAs) and mRNAs between conidial and mycelial stages to investigate the roles of milRNAs in regulating the expression of target genes in T. rubrum.

RESULTS: A total of 158 conserved milRNAs and 12 novel milRNAs were identified in our study, corresponding to 5470 target genes, which were involved in various essential biological pathways. In addition, 137 target genes corresponding to 21 milRNAs were concurrent differentially expressed between the conidial and mycelial stages. Among these 137 target genes, 64 genes showed the opposite trend to their corresponding milRNAs in expression difference between the two stages, indicating possible negative regulation. Furthermore, 46% of differentially expressed target genes are involved in transcription, transcriptional and post-transcriptional regulation. Our results indicate that milRNAs might associate with other regulatory elements to control gene expression at both transcriptional and post-transcriptional level.

CONCLUSIONS: This study provides the first analysis of milRNA expression profile in T. rubrum as well as dermatophytes in general. The results revealed the roles of milRNAs in regulating gene expression between the two major growth stages of this fungus. Our study deepens our understanding of T. rubrum and will serve as a foundation for further investigations to combat this fungus.}, } @article {pmid30547761, year = {2018}, author = {Morales-Cruz, A and Figueroa-Balderas, R and García, JF and Tran, E and Rolshausen, PE and Baumgartner, K and Cantu, D}, title = {Profiling grapevine trunk pathogens in planta: a case for community-targeted DNA metabarcoding.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {214}, doi = {10.1186/s12866-018-1343-0}, pmid = {30547761}, issn = {1471-2180}, support = {2016-1798//American Vineyard Foundation/ ; 2017-1798//American Vineyard Foundation/ ; 2018-1798//American Vineyard Foundation/ ; 2012-51181-19954//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: DNA metabarcoding, commonly used in exploratory microbial ecology studies, is a promising method for the simultaneous in planta-detection of multiple pathogens associated with disease complexes, such as the grapevine trunk diseases. Profiling of pathogen communities associated with grapevine trunk diseases is particularly challenging, due to the presence within an individual wood lesion of multiple co-infecting trunk pathogens and other wood-colonizing fungi, which span a broad range of taxa in the fungal kingdom. As such, we designed metabarcoding primers, using as template the ribosomal internal transcribed spacer of grapevine trunk-associated ascomycete fungi (GTAA) and compared them to two universal primer widely used in microbial ecology.

RESULTS: We first performed in silico simulations and then tested the primers by high-throughput amplicon sequencing of (i) multiple combinations of mock communities, (ii) time-course experiments with controlled inoculations, and (iii) diseased field samples from vineyards under natural levels of infection. All analyses showed that GTAA had greater affinity and sensitivity, compared to those of the universal primers. Importantly, with GTAA, profiling of mock communities and comparisons with shotgun-sequencing metagenomics of field samples gave an accurate representation of genera of important trunk pathogens, namely Phaeomoniella, Phaeoacremonium, and Eutypa, the abundances of which were over- or under-estimated with universal primers.

CONCLUSIONS: Overall, our findings not only demonstrate that DNA metabarcoding gives qualitatively and quantitatively accurate results when applied to grapevine trunk diseases, but also that primer customization and testing are crucial to ensure the validity of DNA metabarcoding results.}, } @article {pmid30547757, year = {2018}, author = {Arathimos, R and Sharp, GC and Granell, R and Tilling, K and Relton, CL}, title = {Associations of sex hormone-binding globulin and testosterone with genome-wide DNA methylation.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {113}, doi = {10.1186/s12863-018-0703-y}, pmid = {30547757}, issn = {1471-2156}, support = {//Wellcome Trust/United Kingdom ; MC_UU_00011/5 and MC_UU_00011/3//Medical Research Council/United Kingdom ; ES/N000498/1//Economic and Social Research Council/ ; }, abstract = {BACKGROUND: Levels of sex hormone-binding globulin (SHBG) and the androgen testosterone have been associated with risk of diseases throughout the lifecourse. Although both SHBG and testosterone have been shown to be highly heritable, only a fraction of that heritability has been explained by genetic studies. Epigenetic modifications such as DNA methylation may explain some of the missing heritability and could potentially inform biological knowledge of endocrine disease mechanisms involved in development of later life disease. Using data from the Avon Longitudinal Study of Parents and Children (ALSPAC), we explored cross-sectional associations of SHBG, total testosterone and bioavailable testosterone in childhood (males only) and adolescence (both males and females) with genome-wide DNA methylation. We also report associations of a SHBG polymorphism (rs12150660) with DNA methylation, which leads to differential levels of SHBG in carriers, as a genetic proxy of circulating SHBG levels.

RESULTS: We identified several novel sites and genomic regions where levels of SHBG, total testosterone, and bioavailable testosterone were associated with DNA methylation, including one region associated with total testosterone in males (annotated to the KLHL31 gene) in both childhood and adolescence and a second region associated with bioavailable testosterone (annotated to the CMYA5 gene) at both time-points. We also identified one region where both SHBG and bioavailable testosterone in males in childhood (annotated to the ZNF718 gene) was associated with DNA methylation.

CONCLUSION: Our findings have important implications in the understanding of the biological processes of SHBG and testosterone, with the potential for future work to determine the molecular mechanisms that could underpin these associations.}, } @article {pmid30547756, year = {2018}, author = {Ji, T and Li, S and Li, L and Huang, M and Wang, X and Wei, M and Shi, Q and Li, Y and Gong, B and Yang, F}, title = {Cucumber Phospholipase D alpha gene overexpression in tobacco enhanced drought stress tolerance by regulating stomatal closure and lipid peroxidation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {355}, doi = {10.1186/s12870-018-1592-y}, pmid = {30547756}, issn = {1471-2229}, support = {31372060//National Natural Sciences Foundations of China/ ; }, mesh = {Abscisic Acid/metabolism ; Cucumis sativus/*genetics ; Droughts ; Gene Expression Regulation, Plant ; Lipid Peroxidation/genetics/physiology ; Malondialdehyde/metabolism ; Phosphatidic Acids/*genetics/metabolism ; Phospholipase D/*genetics/metabolism ; Plant Proteins/genetics/metabolism ; Plant Stomata/physiology ; Plants, Genetically Modified ; Proline/metabolism ; Stress, Physiological/*genetics ; Tobacco/genetics/*physiology ; Water/metabolism ; }, abstract = {BACKGROUND: Plant phospholipase D (PLD), which can hydrolyze membrane phospholipids to produce phosphatidic acid (PA), a secondary signaling molecule, has been proposed to function in diverse plant stress responses. Both PLD and PA play key roles in plant growth, development, and cellular processes. PLD was suggested to mediate the regulation of stomatal movements by abscisic acid (ABA) as a response to water deficit. In this research, we characterized the roles of the cucumber phospholipase D alpha gene (CsPLDα, GenBank accession number EF363796) in the growth and tolerance of transgenic tobacco (Nicotiana tabacum) to drought stress.

RESULTS: The CsPLDα overexpression in tobacco lines correlated with the ABA synthesis and metabolism, regulated the rapid stomatal closure in drought stress, and reduced the water loss. The NtNCED1 expression levels in the transgenic lines and wild type (WT) were sharply up-regulated after 16 days of drought stress compared with those before treatment, and the expression level in the transgenic lines was significantly higher than that in the WT. The NtAOG expression level evidently improved after 8 and 16 days compared with that at 0 day of treatment and was significantly lower in the transgenic lines than in the WT. The ABA content in the transgenic lines was significantly higher than that in the WT. The CsPLDα overexpression could increase the osmolyte content and reduce the ion leakage. The proline, soluble sugar, and soluble protein contents significantly increased. By contrast, the electrolytic leakage and malondialdehyde accumulation in leaves significantly decreased. The shoot and root fresh and dry weights of the overexpression lines significantly increased. These results indicated that a significant correlation between CsPLDα overexpression and improved resistance to water deficit.

CONCLUSIONS: The plants with overexpressed CsPLDα exhibited lower water loss, higher leaf relative water content, and heavier fresh and dry matter accumulation than the WT. We proposed that CsPLDα was involved in the ABA-dependent pathway in mediating the stomatal closure and preventing the elevation of intracellular solute potential.}, } @article {pmid30547751, year = {2018}, author = {Yang, H and Yang, M and Fang, S and Huang, X and He, M and Ke, S and Gao, J and Wu, J and Zhou, Y and Fu, H and Chen, C and Huang, L}, title = {Evaluating the profound effect of gut microbiome on host appetite in pigs.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {215}, doi = {10.1186/s12866-018-1364-8}, pmid = {30547751}, issn = {1471-2180}, support = {31472071//National Natural Science Foundation of China/ ; 31702103//National Natural Science Foundation of China/ ; BX201700102//National Postdoctoral Program for Innovative Talents/ ; }, abstract = {BACKGROUND: There are growing evidences showing that gut microbiota should play an important role in host appetite and feeding behavior. However, what kind of microbe(s) and how they affect porcine appetite remain unknown.

RESULTS: In this study, 280 commercial Duroc pigs were raised in a testing station with the circadian feeding behavior records for a continuous period of 30-100 kg. We first analyzed the influences of host gender and genetics in porcine average daily feed intake (ADFI), but no significant effect was observed. We found that the Prevotella-predominant enterotype had a higher ADFI than the Treponema enterotype-like group. Furthermore, 12 out of the 18 OTUs positively associated with the ADFI were annotated to Prevotella, and Prevotella was the hub bacteria in the co-abundance network. These results suggested that Prevotella might be a keystone bacterial taxon for increasing host feed intake. However, some bacteria producing short-chain fatty acids (SCFAs) and lactic acid (e.g. Ruminococcaceae and Lactobacillus) showed negative associations with the ADFI. Predicted function capacity analysis showed that the genes for amino acid biosynthesis had significantly different enrichment between pigs with high and low ADFI.

CONCLUSIONS: The present study provided important information on the profound effect of gut microbiota on porcine appetite and feeding behavior. This will profit us to regulate porcine appetite through modulating the gut microbiome in the pig industry.}, } @article {pmid30547746, year = {2018}, author = {Fitzgerald, CB and Shkoporov, AN and Sutton, TDS and Chaplin, AV and Velayudhan, V and Ross, RP and Hill, C}, title = {Comparative analysis of Faecalibacterium prausnitzii genomes shows a high level of genome plasticity and warrants separation into new species-level taxa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {931}, doi = {10.1186/s12864-018-5313-6}, pmid = {30547746}, issn = {1471-2164}, support = {SFI/12/RC/2273//Science Foundation Ireland/Ireland ; SFI/14/SP APC/B3032//Science Foundation Ireland (IE)/ ; NA//Janssen Biotech (US)/ ; }, abstract = {BACKGROUND: Faecalibacterium prausnitzii is a ubiquitous member of the human gut microbiome, constituting up to 15% of the total bacteria in the human gut. Substantial evidence connects decreased levels of F. prausnitzii with the onset and progression of certain forms of inflammatory bowel disease, which has been attributed to its anti-inflammatory potential. Two phylogroups of F. prausnitzii have been identified, with a decrease in phylogroup I being a more sensitive marker of intestinal inflammation. Much of the genomic and physiological data available to date was collected using phylogroup II strains. Little analysis of F. prausnitzii genomes has been performed so far and genetic differences between phylogroups I and II are poorly understood.

RESULTS: In this study we sequenced 11 additional F. prausnitzii genomes and performed comparative genomics to investigate intraspecies diversity, functional gene complement and the mobilome of 31 high-quality draft and complete genomes. We reveal a very low level of average nucleotide identity among F. prausnitzii genomes and a high level of genome plasticity. Two genomogroups can be separated based on differences in functional gene complement, albeit that this division does not fully agree with separation based on conserved gene phylogeny, highlighting the importance of horizontal gene transfer in shaping F. prausnitzii genomes. The difference between the two genomogroups is mainly in the complement of genes associated with catabolism of carbohydrates (such as a predicted sialidase gene in genomogroup I) and amino acids, as well as defense mechanisms.

CONCLUSIONS: Based on the combination of ANI of genomic sequences, phylogenetic analysis of core proteomes and functional differences we propose to separate the species F. prausnitzii into two new species level taxa: F. prausnitzii sensu stricto (neotype strain A2-165T = DSM 17677T = JCM 31915T) and F. moorei sp. nov. (type strain ATCC 27768T = NCIMB 13872T).}, } @article {pmid30547744, year = {2018}, author = {Finch, JTD and Power, SA and Welbergen, JA and Cook, JM}, title = {Two's company, three's a crowd: co-occurring pollinators and parasite species in Breynia oblongifolia (Phyllanthaceae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {193}, doi = {10.1186/s12862-018-1314-y}, pmid = {30547744}, issn = {1471-2148}, mesh = {Animals ; Bayes Theorem ; DNA Barcoding, Taxonomic ; Female ; Geography ; Male ; Malpighiaceae/*parasitology ; Moths/anatomy & histology/physiology/ultrastructure ; New South Wales ; Ovary/cytology ; Oviposition ; Ovule/cytology ; Parasites/anatomy & histology/*physiology/ultrastructure ; Phylogeny ; Pollination/*physiology ; Species Specificity ; }, abstract = {BACKGROUND: Obligate pollination mutualisms (OPMs) are specialized interactions in which female pollinators transport pollen between the male and female flowers of a single plant species and then lay eggs into those same flowers. The pollinator offspring hatch and feed upon some or all of the developing ovules pollinated by their mothers. Strong trait matching between plants and their pollinators in OPMs is expected to result in reciprocal partner specificity i.e., a single pollinator species using a single plant species and vice versa, and strict co-speciation. These issues have been studied extensively in figs and fig wasps, but little in the more recently discovered co-diversification of Epicephala moths and their Phyllanthaceae hosts. OPMs involving Epicephala moths are believed occur in approximately 500 species of Phyllanthaceae, making it the second largest OPM group after the Ficus radiation (> 750 species). In this study, we used a mixture of DNA barcoding, genital morphology and behavioral observations to determine the number of Epicephala moth species inhabiting the fruits of Breynia oblongifolia, their geographic distribution, pollinating behavior and phylogenetic relationships.

RESULTS: We found that B. oblongifolia hosts two species of pollinator that co-occurred at all study sites, violating the assumption of reciprocal specificity. Male and female genital morphologies both differed considerably between the two moth species. In particular, females differed in the shape of their ovipositors, eggs and oviposition sites. Phylogenetic analyses indicated that the two Epicephala spp. on B. oblongifolia likely co-exist due to a host switch. In addition, we discovered that Breynia fruits are also often inhabited by a third moth, an undescribed species of Herpystis, which is a non-pollinating seed parasite.

CONCLUSIONS: Our study reveals new complexity in interactions between Phyllantheae and Epicephala pollinators and highlights that host switching, co-speciation and non-pollinating seed parasites can shape species interactions in OPMs. Our finding that co-occurring Epicephala species have contrasting oviposition modes parallels other studies and suggests that such traits are important in Epicephala species coexistence.}, } @article {pmid30547742, year = {2018}, author = {Cao, H}, title = {Identification of the major diacylglycerol acyltransferase mRNA in mouse adipocytes and macrophages.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {11}, doi = {10.1186/s12858-018-0103-y}, pmid = {30547742}, issn = {1471-2091}, support = {6054-41000-103-00-D//USDA-ARS Quality and Utilization of Agricultural Products National Program/ ; }, abstract = {BACKGROUND: Triacylglycerols (TAGs) are the major form of energy storage in eukaryotes. Diacylglycerol acyltransferases (DGATs) catalyze the final and rate-limiting step of TAG biosynthesis. Mammalian DGATs are classified into DGAT1 and DGAT2 subfamilies. It was unclear which DGAT was the major isoform expressed in animal cells. The objective was to identify the major DGAT mRNA expressed in cultured mouse adipocytes and macrophages and compared it to that expressed in tung tree seeds.

METHODS: qPCR evaluated DGAT mRNA levels in mouse 3 T3-L1 adipocytes and RAW264.7 macrophages and tung tree seeds.

RESULTS: TaqMan qPCR showed that DGAT2 mRNA levels were 10-30 fold higher than DGAT1 in adipocytes and macrophages, and DGAT mRNA levels in adipocytes were 50-100-fold higher than those in macrophages. In contrast, the anti-inflammatory tristetraprolin/zinc finger protein 36 (TTP/ZFP36) mRNA levels were 2-4-fold higher in macrophages than those in adipocytes and similar to DGAT1 in adipocytes but 100-fold higher than DGAT1 in macrophages. SYBR Green qPCR analyses confirmed TaqMan qPCR results. DGAT2 mRNA as the major DGAT mRNA in the mouse cells was similar to that in tung tree seeds where DGAT2 mRNA levels were 10-20-fold higher than DGAT1 or DGAT3.

CONCLUSION: The results demonstrated that DGAT2 mRNA was the major form of DGAT mRNA expressed in mouse adipocytes and macrophages and tung tree seeds.}, } @article {pmid30547741, year = {2018}, author = {Lu, Y and Johnston, PR and Dennis, SR and Monaghan, MT and John, U and Spaak, P and Wolinska, J}, title = {Daphnia galeata responds to the exposure to an ichthyosporean gut parasite by down-regulation of immunity and lipid metabolism.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {932}, doi = {10.1186/s12864-018-5312-7}, pmid = {30547741}, issn = {1471-2164}, support = {WO 1587/6-1//Deutsche Forschungsgemeinschaft/ ; 310030L 166628//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, abstract = {BACKGROUND: Regulatory circuits of infection in the emerging experimental model system, water flea Daphnia and their microparasites, remain largely unknown. Here we provide the first molecular insights into the response of Daphnia galeata to its highly virulent and common parasite Caullerya mesnili, an ichthyosporean that infects the gut epithelium. We generated a transcriptomic dataset using RNAseq from parasite-exposed (vs. control) Daphnia, at two time points (4 and 48 h) after parasite exposure.

RESULTS: We found a down-regulation of metabolism and immunity-related genes, at 48 h (but not 4 h) after parasite exposure. These genes are involved in lipid metabolism and fatty acid biosynthesis, as well as microbe recognition (e.g. c-type lectins) and pathogen attack (e.g. gut chitin).

CONCLUSIONS: General metabolic suppression implies host energy shift from reproduction to survival, which is in agreement with the known drastic reduction in Daphnia fecundity after Caullerya infection. The down-regulation of gut chitin indicates a possible interaction between the peritrophic matrix and the evading host immune system. Our study provides the first description of host transcriptional responses in this very promising host-parasite experimental system.}, } @article {pmid30547739, year = {2018}, author = {Domanska, D and Kanduri, C and Simovski, B and Sandve, GK}, title = {Mind the gaps: overlooking inaccessible regions confounds statistical testing in genome analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {481}, doi = {10.1186/s12859-018-2438-1}, pmid = {30547739}, issn = {1471-2105}, mesh = {*Confounding Factors (Epidemiology) ; *Genome, Human ; Genomics ; *High-Throughput Nucleotide Sequencing ; Humans ; *Statistics as Topic ; }, abstract = {BACKGROUND: The current versions of reference genome assemblies still contain gaps represented by stretches of Ns. Since high throughput sequencing reads cannot be mapped to those gap regions, the regions are depleted of experimental data. Moreover, several technology platforms assay a targeted portion of the genomic sequence, meaning that regions from the unassayed portion of the genomic sequence cannot be detected in those experiments. We here refer to all such regions as inaccessible regions, and hypothesize that ignoring these regions in the null model may increase false findings in statistical testing of colocalization of genomic features.

RESULTS: Our explorative analyses confirm that the genomic regions in public genomic tracks intersect very little with assembly gaps of human reference genomes (hg19 and hg38). The little intersection was observed only at the beginning and end portions of the gap regions. Further, we simulated a set of synthetic tracks by matching the properties of real genomic tracks in a way that nullified any true association between them. This allowed us to test our hypothesis that not avoiding inaccessible regions (as represented by assembly gaps) in the null model would result in spurious inflation of statistical significance. We contrasted the distributions of test statistics and p-values of Monte Carlo-based permutation tests that either avoided or did not avoid assembly gaps in the null model when testing colocalization between a pair of tracks. We observed that the statistical tests that did not account for assembly gaps in the null model resulted in a distribution of the test statistic that is shifted to the right and a distribution of p-values that is shifted to the left (indicating inflated significance). We observed a similar level of inflated significance in hg19 and hg38, despite assembly gaps covering a smaller proportion of the latter reference genome.

CONCLUSION: We provide empirical evidence demonstrating that inaccessible regions, even when covering only a few percentages of the genome, can lead to a substantial amount of false findings if not accounted for in statistical colocalization analysis.}, } @article {pmid30547367, year = {2018}, author = {Pleyer, HL and Strasdeit, H and Fox, S}, title = {A Possible Prebiotic Ancestry of Porphyrin-Type Protein Cofactors.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11084-018-9567-4}, pmid = {30547367}, issn = {1573-0875}, support = {LGFG Doctoral Fellowship//State of Baden-Wuerttemberg/ ; }, abstract = {In previous experiments that simulated conditions on primordial volcanic islands, we demonstrated the abiotic formation of hydrophobic porphyrins. The present study focused on the question whether such porphyrins can be metalated by prebiotically plausible metal ion sources. We used water-insoluble octaethylporphyrin (H2oep) as a model compound. Experiments were conducted in a nitrogen atmosphere under cyclic wet-dry conditions in order to simulate the fluctuating environment in prebiotic rock pools. Wetting-drying proved to be a crucial factor. Significant yields of the metalloporphyrins (20-78% with respect to H2oep) were obtained from the soluble salts MCl2 (M = Mg, Fe, Co, Ni and Cu) in freshwater. Even almost insoluble minerals and rocks metalated the porphyrin. Basalt (an iron source, 11% yield), synthetic jaipurite (CoS, 33%) and synthetic covellite (CuS, 57%) were most efficient. Basalt, magnetite and FeCl2 gave considerably higher yields in artificial seawater than in freshwater. From iron sources, the highest yields, however, were obtained in an acidic medium (hydrochloric acid with an initial pH of 2.1). Under these conditions, iron meteorites also metalated the porphyrin. Acidic conditions were considered because they are known to occur during eruptions on volcanic islands. Octaethylporphyrinatomagnesium(II) did not form in acidic medium and was unstable towards dissolved Fe2+. It is therefore questionable whether magnesium porphyrins, i.e. possible ancestors of chlorophyll, could have accumulated in primordial rock pools. However, abiotically formed ancestors of the modern cofactors heme (Fe), B12 (Co), and F430 (Ni) may have been available to hypothetical protometabolisms and early organisms.}, } @article {pmid30546255, year = {2018}, author = {Yampolskiy, RV}, title = {Why We Do Not Evolve Software? Analysis of Evolutionary Algorithms.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318815906}, pmid = {30546255}, issn = {1176-9343}, abstract = {In this article, we review the state-of-the-art results in evolutionary computation and observe that we do not evolve nontrivial software from scratch and with no human intervention. A number of possible explanations are considered, but we conclude that computational complexity of the problem prevents it from being solved as currently attempted. A detailed analysis of necessary and available computational resources is provided to support our findings.}, } @article {pmid30546254, year = {2018}, author = {Nakamura, Y}, title = {Prediction of Horizontally and Widely Transferred Genes in Prokaryotes.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318810785}, pmid = {30546254}, issn = {1176-9343}, abstract = {Horizontal gene transfer (HGT) is the process whereby an organism acquires exogenous genes (horizontally transferred genes or HT genes) that are not inherited from the parent, but are derived from another organism. In prokaryotes, HGT has been considered as one of the important driving forces of evolution. Previously, genome-wide analyses have been conducted for estimating the proportion of HT genes in prokaryotic genomes, but the number of species examined at the time was limited, and gene annotation was relatively poor. Currently, tens of thousands of prokaryotic genomes have been published and gene annotation resources have improved. In the present study, HT gene prediction method was modified so that the estimate was robust to gene length, conducting a comprehensive search using 3017 representative prokaryotic genomes belonging to 1348 species. The result showed that an average of 13% (ranging from 0% to 30% across species) of protein-coding genes was predicted as being of horizontal origin. The proportion of the predicted HT genes per species was associated with the species' habitat, while a positive correlation between the proportion and genomic nucleotide frequency was also observed. Moreover, the functions of the predicted HT genes were inferred and compared according to two popular databases, the Clusters of Orthologous Groups and the Kyoto Encyclopedia of Genes and Genomes. As a result, both databases indicated that many of the widely transferred genes were involved in mobile genetic elements (transposons, phages, and plasmids) as expected. Notably, the present study predicted that six as-yet-uncharacterized genes were widely distributed HT genes, and therefore, will be interesting targets for evolutionary studies. Thus, this study demonstrates that a data-driven approach using massive sequence data may contribute to a broader understanding of HGT in prokaryotes.}, } @article {pmid30546139, year = {2018}, author = {Purro, SA and Farrow, MA and Linehan, J and Nazari, T and Thomas, DX and Chen, Z and Mengel, D and Saito, T and Saido, T and Rudge, P and Brandner, S and Walsh, DM and Collinge, J}, title = {Transmission of amyloid-β protein pathology from cadaveric pituitary growth hormone.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {415-419}, doi = {10.1038/s41586-018-0790-y}, pmid = {30546139}, issn = {1476-4687}, support = {R01 AG046275/AG/NIA NIH HHS/United States ; }, abstract = {We previously reported1 the presence of amyloid-β protein (Aβ) deposits in individuals with Creutzfeldt-Jakob disease (CJD) who had been treated during childhood with human cadaveric pituitary-derived growth hormone (c-hGH) contaminated with prions. The marked deposition of parenchymal and vascular Aβ in these relatively young individuals with treatment-induced (iatrogenic) CJD (iCJD), in contrast to other prion-disease patients and population controls, allied with the ability of Alzheimer's disease brain homogenates to seed Aβ deposition in laboratory animals, led us to argue that the implicated c-hGH batches might have been contaminated with Aβ seeds as well as with prions. However, this was necessarily an association, and not an experimental, study in humans and causality could not be concluded. Given the public health importance of our hypothesis, we proceeded to identify and biochemically analyse archived vials of c-hGH. Here we show that certain c-hGH batches to which patients with iCJD and Aβ pathology were exposed have substantial levels of Aβ40, Aβ42 and tau proteins, and that this material can seed the formation of Aβ plaques and cerebral Aβ-amyloid angiopathy in intracerebrally inoculated mice expressing a mutant, humanized amyloid precursor protein. These results confirm the presence of Aβ seeds in archived c-hGH vials and are consistent with the hypothesized iatrogenic human transmission of Aβ pathology. This experimental confirmation has implications for both the prevention and the treatment of Alzheimer's disease, and should prompt a review of the risk of iatrogenic transmission of Aβ seeds by medical and surgical procedures long recognized to pose a risk of accidental prion transmission2,3.}, } @article {pmid30546138, year = {2018}, author = {Tatalovic, M}, title = {The best science images of the year: 2018 in pictures.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {318-323}, doi = {10.1038/d41586-018-07684-4}, pmid = {30546138}, issn = {1476-4687}, } @article {pmid30546137, year = {2018}, author = {Huynh, TV and Holtzman, DM}, title = {Amyloid-β 'seeds' in old vials of growth hormone.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {354-355}, doi = {10.1038/d41586-018-07604-6}, pmid = {30546137}, issn = {1476-4687}, } @article {pmid30546113, year = {2018}, author = {Brennan, CA and Garrett, WS}, title = {Fusobacterium nucleatum - symbiont, opportunist and oncobacterium.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0129-6}, pmid = {30546113}, issn = {1740-1534}, abstract = {Fusobacterium nucleatum has long been found to cause opportunistic infections and has recently been implicated in colorectal cancer; however, it is a common member of the oral microbiota and can have a symbiotic relationship with its hosts. To address this dissonance, we explore the diversity and niches of fusobacteria and reconsider historic fusobacterial taxonomy in the context of current technology. We also undertake a critical reappraisal of fusobacteria with a focus on F. nucleatum as a mutualist, infectious agent and oncogenic microorganism. In this Review, we delve into recent insights and future directions for fusobacterial research, including the current genetic toolkit, our evolving understanding of its mechanistic role in promoting colorectal cancer and the challenges of developing diagnostics and therapeutics for F. nucleatum.}, } @article {pmid30546107, year = {2018}, author = {Beaulaurier, J and Schadt, EE and Fang, G}, title = {Deciphering bacterial epigenomes using modern sequencing technologies.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41576-018-0081-3}, pmid = {30546107}, issn = {1471-0064}, support = {R01 GM114472/GM/NIGMS NIH HHS/United States ; R01 GM128955/GM/NIGMS NIH HHS/United States ; }, abstract = {Prokaryotic DNA contains three types of methylation: N6-methyladenine, N4-methylcytosine and 5-methylcytosine. The lack of tools to analyse the frequency and distribution of methylated residues in bacterial genomes has prevented a full understanding of their functions. Now, advances in DNA sequencing technology, including single-molecule, real-time sequencing and nanopore-based sequencing, have provided new opportunities for systematic detection of all three forms of methylated DNA at a genome-wide scale and offer unprecedented opportunities for achieving a more complete understanding of bacterial epigenomes. Indeed, as the number of mapped bacterial methylomes approaches 2,000, increasing evidence supports roles for methylation in regulation of gene expression, virulence and pathogen-host interactions.}, } @article {pmid30546100, year = {2019}, author = {Shen, P and Lees, JA and Bee, GCW and Brown, SP and Weiser, JN}, title = {Pneumococcal quorum sensing drives an asymmetric owner-intruder competitive strategy during carriage via the competence regulon.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {198-208}, doi = {10.1038/s41564-018-0314-4}, pmid = {30546100}, issn = {2058-5276}, support = {R01 AI105168/AI/NIAID NIH HHS/United States ; }, abstract = {Competition among microorganisms is a key determinant of successful host colonization and persistence. For Streptococcus pneumoniae, lower than predicted rates of co-colonizing strains suggest a competitive advantage for resident bacteria over newcomers. In light of evolutionary theory, we hypothesized that S. pneumoniae use owner-intruder asymmetries to settle contests, leading to the disproportionate success of the initial resident 'owner', regardless of the genetic identity of the 'intruder'. We investigated the determinants of within-host competitive success utilizing S. pneumoniae colonization of the upper respiratory tract of infant mice. Within 6 h, colonization by the resident inhibited colonization by an isogenic challenger. The competitive advantage of the resident was dependent on quorum sensing via the competence (Com) regulon and downstream choline binding protein D (CbpD) and on the competence-induced bacteriocins A and B (CibAB) implicated in fratricide. CbpD and CibAB are highly conserved across pneumococcal lineages, indicating evolutionary advantages for asymmetric competitive strategies within the species. Mathematical modelling supported a significant role for quorum sensing via the Com regulon in competition, even for strains with different competitive advantages. Our study suggests that asymmetric owner-intruder competitive strategies do not require complex cognition and are used by a major human pathogen to determine 'ownership' of human hosts.}, } @article {pmid30546099, year = {2019}, author = {Grubaugh, ND and Ladner, JT and Lemey, P and Pybus, OG and Rambaut, A and Holmes, EC and Andersen, KG}, title = {Tracking virus outbreaks in the twenty-first century.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {10-19}, doi = {10.1038/s41564-018-0296-2}, pmid = {30546099}, issn = {2058-5276}, support = {U19 AI135995/AI/NIAID NIH HHS/United States ; T32 AI007244/AI/NIAID NIH HHS/United States ; R21 AI137690/AI/NIAID NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; //Wellcome Trust/United Kingdom ; HHSN272201400048C/AI/NIAID NIH HHS/United States ; }, abstract = {Emerging viruses have the potential to impose substantial mortality, morbidity and economic burdens on human populations. Tracking the spread of infectious diseases to assist in their control has traditionally relied on the analysis of case data gathered as the outbreak proceeds. Here, we describe how many of the key questions in infectious disease epidemiology, from the initial detection and characterization of outbreak viruses, to transmission chain tracking and outbreak mapping, can now be much more accurately addressed using recent advances in virus sequencing and phylogenetics. We highlight the utility of this approach with the hypothetical outbreak of an unknown pathogen, 'Disease X', suggested by the World Health Organization to be a potential cause of a future major epidemic. We also outline the requirements and challenges, including the need for flexible platforms that generate sequence data in real-time, and for these data to be shared as widely and openly as possible.}, } @article {pmid30546094, year = {2019}, author = {Libertucci, J and Young, VB}, title = {The role of the microbiota in infectious diseases.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {35-45}, doi = {10.1038/s41564-018-0278-4}, pmid = {30546094}, issn = {2058-5276}, abstract = {The human body is colonized by a diverse community of microorganisms collectively referred to as the microbiota. Here, we describe how the human microbiota influences susceptibility to infectious diseases using examples from the respiratory, gastrointestinal and female reproductive tract. We will discuss how interactions between the host, the indigenous microbiota and non-native microorganisms, including bacteria, viruses and fungi, can alter the outcome of infections. This Review Article will highlight the complex mechanisms by which the microbiota mediates colonization resistance, both directly and indirectly, against infectious agents. Strategies for the therapeutic modulation of the microbiota to prevent or treat infectious diseases will be discussed, and we will review potential therapies that directly target the microbiota, including prebiotics, probiotics, synbiotics and faecal microbiota transplantation.}, } @article {pmid30546093, year = {2019}, author = {Land, KJ and Boeras, DI and Chen, XS and Ramsay, AR and Peeling, RW}, title = {REASSURED diagnostics to inform disease control strategies, strengthen health systems and improve patient outcomes.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {46-54}, doi = {10.1038/s41564-018-0295-3}, pmid = {30546093}, issn = {2058-5276}, abstract = {Lack of access to quality diagnostics remains a major contributor to health burden in resource-limited settings. It has been more than 10 years since ASSURED (affordable, sensitive, specific, user-friendly, rapid, equipment-free, delivered) was coined to describe the ideal test to meet the needs of the developing world. Since its initial publication, technological innovations have led to the development of diagnostics that address the ASSURED criteria, but challenges remain. From this perspective, we assess factors contributing to the success and failure of ASSURED diagnostics, lessons learnt in the implementation of ASSURED tests over the past decade, and highlight additional conditions that should be considered in addressing point-of-care needs. With rapid advances in digital technology and mobile health (m-health), future diagnostics should incorporate these elements to give us REASSURED diagnostic systems that can inform disease control strategies in real-time, strengthen the efficiency of health care systems and improve patient outcomes.}, } @article {pmid30545919, year = {2018}, author = {Yuan, L and Kenny, SJ and Hemmati, J and Xu, K and Schekman, R}, title = {TANGO1 and SEC12 are copackaged with procollagen I to facilitate the generation of large COPII carriers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12255-E12264}, doi = {10.1073/pnas.1814810115}, pmid = {30545919}, issn = {1091-6490}, abstract = {Large coat protein complex II (COPII)-coated vesicles serve to convey the large cargo procollagen I (PC1) from the endoplasmic reticulum (ER). The link between large cargo in the lumen of the ER and modulation of the COPII machinery remains unresolved. TANGO1 is required for PC secretion and interacts with PC and COPII on opposite sides of the ER membrane, but evidence suggests that TANGO1 is retained in the ER, and not included in normal size (<100 nm) COPII vesicles. Here we show that TANGO1 is exported out of the ER in large COPII-coated PC1 carriers, and retrieved back to the ER by the retrograde coat, COPI, mediated by the C-terminal RDEL retrieval sequence of HSP47. TANGO1 is known to target the COPII initiation factor SEC12 to ER exit sites through an interacting protein, cTAGE5. SEC12 is important for the growth of COPII vesicles, but it is not sorted into small budded vesicles. We found both cTAGE5 and SEC12 were exported with TANGO1 in large COPII carriers. In contrast to its exclusion from small transport vesicles, SEC12 was particularly enriched around ER membranes and large COPII carriers that contained PC1. We constructed a split GFP system to recapitulate the targeting of SEC12 to PC1 via the luminal domain of TANGO1. The minimal targeting system enriched SEC12 around PC1 and generated large PC1 carriers. We conclude that TANGO1, cTAGE5, and SEC12 are copacked with PC1 into COPII carriers to increase the size of COPII, thus ensuring the capture of large cargo.}, } @article {pmid30545918, year = {2018}, author = {Pedersen, M and Zalesky, A and Omidvarnia, A and Jackson, GD}, title = {Multilayer network switching rate predicts brain performance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13376-13381}, doi = {10.1073/pnas.1814785115}, pmid = {30545918}, issn = {1091-6490}, abstract = {Large-scale brain dynamics are characterized by repeating spatiotemporal connectivity patterns that reflect a range of putative different brain states that underlie the dynamic repertoire of brain functions. The role of transition between brain networks is poorly understood, and whether switching between these states is important for behavior has been little studied. Our aim was to model switching between functional brain networks using multilayer network methods and test for associations between model parameters and behavioral measures. We calculated time-resolved fMRI connectivity in 1,003 healthy human adults from the Human Connectome Project. The time-resolved fMRI connectivity data were used to generate a spatiotemporal multilayer modularity model enabling us to quantify network switching, which we define as the rate at which each brain region transits between different networks. We found (i) an inverse relationship between network switching and connectivity dynamics, where the latter was defined in terms of time-resolved fMRI connections with variance in time that significantly exceeded phase-randomized surrogate data; (ii) brain connectivity was lower during intervals of network switching; (iii) brain areas with frequent network switching had greater temporal complexity; (iv) brain areas with high network switching were located in association cortices; and (v) using cross-validated elastic net regression, network switching predicted intersubject variation in working memory performance, planning/reasoning, and amount of sleep. Our findings shed light on the importance of brain dynamics predicting task performance and amount of sleep. The ability to switch between network configurations thus appears to be a fundamental feature of optimal brain function.}, } @article {pmid30545917, year = {2018}, author = {Nauroze, SA and Novelino, LS and Tentzeris, MM and Paulino, GH}, title = {Continuous-range tunable multilayer frequency-selective surfaces using origami and inkjet printing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13210-13215}, doi = {10.1073/pnas.1812486115}, pmid = {30545917}, issn = {1091-6490}, abstract = {The tremendous increase in the number of components in typical electrical and communication modules requires low-cost, flexible and multifunctional sensing, energy harvesting, and communication modules that can readily reconfigure, depending on changes in their environment. Current subtractive manufacturing-based reconfigurable systems offer limited flexibility (limited finite number of discrete reconfiguration states) and have high fabrication cost and time requirements. Thus, this paper introduces an approach to solve the problem by combining additive manufacturing and origami principles to realize tunable electrical components that can be reconfigured over continuous-state ranges from folded (compact) to unfolded (large surface) configurations. Special "bridge-like" structures are introduced along the traces that increase their flexibility, thereby avoiding breakage during folding. These techniques allow creating truly flexible conductive traces that can maintain high conductivity even for large bending angles, further enhancing the states of reconfigurability. To demonstrate the idea, a Miura-Ori pattern is used to fabricate spatial filters-frequency-selective surfaces (FSSs) with dipole resonant elements placed along the fold lines. The electrical length of the dipole elements in these structures changes when the Miura-Ori is folded, which facilitates tunable frequency response for the proposed shape-reconfigurable FSS structure. Higher-order spatial filters are realized by creating multilayer Miura-FSS configurations, which further increase the overall bandwidth of the structure. Such multilayer Miura-FSS structures feature the unprecedented capability of on-the-fly reconfigurability to different specifications (multiple bands, broadband/narrowband bandwidth, wide angle of incidence rejection), requiring neither specialized substrates nor highly complex electronics, holding frames, or fabrication processes.}, } @article {pmid30545916, year = {2018}, author = {Sreenivasan, KR}, title = {Turbulent mixing: A perspective.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1800463115}, pmid = {30545916}, issn = {1091-6490}, abstract = {Mixing of initially distinct substances plays an important role in our daily lives as well as in ecological and technological worlds. From the continuum point of view, which we adopt here, mixing is complete when the substances come together across smallest flow scales determined in part by molecular mechanisms, but important stages of the process occur via the advection of substances by an underlying flow. We know how smooth flows enable mixing but less well the manner in which a turbulent flow influences it; but the latter is the more common occurrence on Earth and in the universe. We focus here on turbulent mixing, with more attention paid to the postmixing state than to the transient process of initiation. In particular, we examine turbulent mixing when the substance is a scalar (i.e., characterized only by the scalar property of its concentration), and the mixing process does not influence the flow itself (i.e., the scalar is "passive"). This is the simplest paradigm of turbulent mixing. Within this paradigm, we discuss how a turbulently mixed state depends on the flow Reynolds number and the Schmidt number of the scalar (the ratio of fluid viscosity to the scalar diffusivity), point out some fundamental aspects of turbulent mixing that render it difficult to be addressed quantitatively, and summarize a set of ideas that help us appreciate its physics in diverse circumstances. We consider the so-called universal and anomalous features and summarize a few model studies that help us understand them both.}, } @article {pmid30545915, year = {2019}, author = {Kaplanov, I and Carmi, Y and Kornetsky, R and Shemesh, A and Shurin, GV and Shurin, MR and Dinarello, CA and Voronov, E and Apte, RN}, title = {Blocking IL-1β reverses the immunosuppression in mouse breast cancer and synergizes with anti-PD-1 for tumor abrogation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {4}, pages = {1361-1369}, doi = {10.1073/pnas.1812266115}, pmid = {30545915}, issn = {1091-6490}, support = {R01 AI015614/AI/NIAID NIH HHS/United States ; R56 AI015614/AI/NIAID NIH HHS/United States ; }, abstract = {Interleukin-1β (IL-1β) is abundant in the tumor microenvironment, where this cytokine can promote tumor growth, but also antitumor activities. We studied IL-1β during early tumor progression using a model of orthotopically introduced 4T1 breast cancer cells. Whereas there is tumor progression and spontaneous metastasis in wild-type (WT) mice, in IL-1β-deficient mice, tumors begin to grow but subsequently regress. This change is due to recruitment and differentiation of inflammatory monocytes in the tumor microenvironment. In WT mice, macrophages heavily infiltrate tumors, but in IL-1β-deficient mice, low levels of the chemokine CCL2 hamper recruitment of monocytes and, together with low levels of colony-stimulating factor-1 (CSF-1), inhibit their differentiation into macrophages. The low levels of macrophages in IL-1β-deficient mice result in a relatively high percentage of CD11b+ dendritic cells (DCs) in the tumors. In WT mice, IL-10 secretion from macrophages is dominant and induces immunosuppression and tumor progression; in contrast, in IL-1β-deficient mice, IL-12 secretion by CD11b+ DCs prevails and supports antitumor immunity. The antitumor immunity in IL-1β-deficient mice includes activated CD8+ lymphocytes expressing IFN-γ, TNF-α, and granzyme B; these cells infiltrate tumors and induce regression. WT mice with 4T1 tumors were treated with either anti-IL-1β or anti-PD-1 Abs, each of which resulted in partial growth inhibition. However, treating mice first with anti-IL-1β Abs followed by anti-PD-1 Abs completely abrogated tumor progression. These data define microenvironmental IL-1β as a master cytokine in tumor progression. In addition to reducing tumor progression, blocking IL-1β facilitates checkpoint inhibition.}, } @article {pmid30545914, year = {2018}, author = {Wang, B and Thachuk, C and Ellington, AD and Winfree, E and Soloveichik, D}, title = {Effective design principles for leakless strand displacement systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12182-E12191}, doi = {10.1073/pnas.1806859115}, pmid = {30545914}, issn = {1091-6490}, abstract = {Artificially designed molecular systems with programmable behaviors have become a valuable tool in chemistry, biology, material science, and medicine. Although information processing in biological regulatory pathways is remarkably robust to error, it remains a challenge to design molecular systems that are similarly robust. With functionality determined entirely by secondary structure of DNA, strand displacement has emerged as a uniquely versatile building block for cell-free biochemical networks. Here, we experimentally investigate a design principle to reduce undesired triggering in the absence of input (leak), a side reaction that critically reduces sensitivity and disrupts the behavior of strand displacement cascades. Inspired by error correction methods exploiting redundancy in electrical engineering, we ensure a higher-energy penalty to leak via logical redundancy. Our design strategy is, in principle, capable of reducing leak to arbitrarily low levels, and we experimentally test two levels of leak reduction for a core "translator" component that converts a signal of one sequence into that of another. We show that the leak was not measurable in the high-redundancy scheme, even for concentrations that are up to 100 times larger than typical. Beyond a single translator, we constructed a fast and low-leak translator cascade of nine strand displacement steps and a logic OR gate circuit consisting of 10 translators, showing that our design principle can be used to effectively reduce leak in more complex chemical systems.}, } @article {pmid30545913, year = {2019}, author = {Melo, JO and Martins, LGC and Barros, BA and Pimenta, MR and Lana, UGP and Duarte, CEM and Pastina, MM and Guimaraes, CT and Schaffert, RE and Kochian, LV and Fontes, EPB and Magalhaes, JV}, title = {Repeat variants for the SbMATE transporter protect sorghum roots from aluminum toxicity by transcriptional interplay in cis and trans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {313-318}, doi = {10.1073/pnas.1808400115}, pmid = {30545913}, issn = {1091-6490}, abstract = {Acidic soils, where aluminum (Al) toxicity is a major agricultural constraint, are globally widespread and are prevalent in developing countries. In sorghum, the root citrate transporter SbMATE confers Al tolerance by protecting root apices from toxic Al3+, but can exhibit reduced expression when introgressed into different lines. We show that allele-specific SbMATE transactivation occurs and is caused by factors located away from SbMATE Using expression-QTL mapping and expression genome-wide association mapping, we establish that SbMATE transcription is controlled in a bipartite fashion, primarily in cis but also in trans Multiallelic promoter transactivation and ChIP analyses demonstrated that intermolecular effects on SbMATE expression arise from a WRKY and a zinc finger-DHHC transcription factor (TF) that bind to and trans-activate the SbMATE promoter. A haplotype analysis in sorghum RILs indicates that the TFs influence SbMATE expression and Al tolerance. Variation in SbMATE expression likely results from changes in tandemly repeated cis sequences flanking a transposable element (a miniature inverted repeat transposable element) insertion in the SbMATE promoter, which are recognized by the Al3+-responsive TFs. According to our model, repeat expansion in Al-tolerant genotypes increases TF recruitment and, hence, SbMATE expression, which is, in turn, lower in Al-sensitive genetic backgrounds as a result of lower TF expression and fewer binding sites. We thus show that even dominant cis regulation of an agronomically important gene can be subjected to precise intermolecular fine-tuning. These concerted cis/trans interactions, which allow the plant to sense and respond to environmental cues, such as Al3+ toxicity, can now be used to increase yields and food security on acidic soils.}, } @article {pmid30545912, year = {2018}, author = {Duval, M and Dar, D and Carvalho, F and Rocha, EPC and Sorek, R and Cossart, P}, title = {HflXr, a homolog of a ribosome-splitting factor, mediates antibiotic resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13359-13364}, doi = {10.1073/pnas.1810555115}, pmid = {30545912}, issn = {1091-6490}, support = {681203//European Research Council/International ; }, abstract = {To overcome the action of antibiotics, bacteria have evolved a variety of different strategies, such as drug modification, target mutation, and efflux pumps. Recently, we performed a genome-wide analysis of Listeria monocytogenes gene expression after growth in the presence of antibiotics, identifying genes that are up-regulated upon antibiotic treatment. One of them, lmo0762, is a homolog of hflX, which encodes a heat shock protein that rescues stalled ribosomes by separating their two subunits. To our knowledge, ribosome splitting has never been described as an antibiotic resistance mechanism. We thus investigated the role of lmo0762 in antibiotic resistance. First, we demonstrated that lmo0762 is an antibiotic resistance gene that confers protection against lincomycin and erythromycin, and that we renamed hflXr (hflX resistance). We show that hflXr expression is regulated by a transcription attenuation mechanism relying on the presence of alternative RNA structures and a small ORF encoding a 14 amino acid peptide containing the RLR motif, characteristic of macrolide resistance genes. We also provide evidence that HflXr is involved in ribosome recycling in presence of antibiotics. Interestingly, L. monocytogenes possesses another copy of hflX, lmo1296, that is not involved in antibiotic resistance. Phylogenetic analysis shows several events of hflXr duplication in prokaryotes and widespread presence of hflXr in Firmicutes. Overall, this study reveals the Listeria hflXr as the founding member of a family of antibiotic resistance genes. The resistance conferred by this gene is probably of importance in the environment and within microbial communities.}, } @article {pmid30545911, year = {2019}, author = {Halstead, SB}, title = {Insights from direct studies on human dengue infections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {17-19}, doi = {10.1073/pnas.1819607116}, pmid = {30545911}, issn = {1091-6490}, } @article {pmid30545910, year = {2018}, author = {Taswell, CA and Costa, VD and Murray, EA and Averbeck, BB}, title = {Ventral striatum's role in learning from gains and losses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12398-E12406}, doi = {10.1073/pnas.1809833115}, pmid = {30545910}, issn = {1091-6490}, abstract = {Adaptive behavior requires animals to learn from experience. Ideally, learning should both promote choices that lead to rewards and reduce choices that lead to losses. Because the ventral striatum (VS) contains neurons that respond to aversive stimuli and aversive stimuli can drive dopamine release in the VS, it is possible that the VS contributes to learning about aversive outcomes, including losses. However, other work suggests that the VS may play a specific role in learning to choose among rewards, with other systems mediating learning from aversive outcomes. To examine the role of the VS in learning from gains and losses, we compared the performance of macaque monkeys with VS lesions and unoperated controls on a reinforcement learning task. In the task, the monkeys gained or lost tokens, which were periodically cashed out for juice, as outcomes for choices. They learned over trials to choose cues associated with gains, and not choose cues associated with losses. We found that monkeys with VS lesions had a deficit in learning to choose between cues that differed in reward magnitude. By contrast, monkeys with VS lesions performed as well as controls when choices involved a potential loss. We also fit reinforcement learning models to the behavior and compared learning rates between groups. Relative to controls, the monkeys with VS lesions had reduced learning rates for gain cues. Therefore, in this task, the VS plays a specific role in learning to choose between rewarding options.}, } @article {pmid30545909, year = {2018}, author = {Sun, P and Chubb, C and Wright, CE and Sperling, G}, title = {High-capacity preconscious processing in concurrent groupings of colored dots.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12153-E12162}, doi = {10.1073/pnas.1814657115}, pmid = {30545909}, issn = {1091-6490}, abstract = {Grouping is a perceptual process in which a subset of stimulus components (a group) is selected for a subsequent-typically implicit-perceptual computation. Grouping is a critical precursor to segmenting objects from the background and ultimately to object recognition. Here, we study grouping by color. We present subjects with 300-ms exposures of 12 dots colored with the same but unknown identical color interspersed among 14 dots of seven different colors. To indicate grouping, subjects point-click the remembered centroid ("center of gravity") of the set of homogeneous dots, of heterogeneous dots, or of all dots. Subjects accurately judge all of these centroids. Furthermore, after a single stimulus exposure, subjects can judge both the heterogeneous and homogeneous centroids, that is, subjects simultaneously group by similarity and by dissimilarity. The centroid paradigm reveals the relative weight of each dot among targets and distractors to the underlying grouping process, offering a more detailed, quantitative description of grouping than was previously possible. A change detection experiment reveals that conscious memory contains less than two dots and their locations, whereas an ideal detector would have to perfectly process at least 15 of 26 dots to match the subjects' centroid judgments-indicating an extraordinary capacity for preconscious grouping. A different color set yielded identical results. Grouping theories that rely on predefined feature maps would fail to explain these results. Rather, the results indicate that preconscious grouping is automatic, flexible, and rapid, and a far more complex process than previously believed.}, } @article {pmid30545908, year = {2018}, author = {Ceh-Pavia, E and Partch, CL}, title = {Regulating behavior with the flip of a translational switch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13151-13153}, doi = {10.1073/pnas.1819247116}, pmid = {30545908}, issn = {1091-6490}, support = {R01 GM107069/GM/NIGMS NIH HHS/United States ; R01 GM121507/GM/NIGMS NIH HHS/United States ; }, } @article {pmid30545890, year = {2018}, author = {Schwerdtfeger, LA}, title = {Spirals of science.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1318}, doi = {10.1126/science.362.6420.1318}, pmid = {30545890}, issn = {1095-9203}, } @article {pmid30545889, year = {2018}, author = {Kistler, L and Maezumi, SY and Gregorio de Souza, J and Przelomska, NAS and Malaquias Costa, F and Smith, O and Loiselle, H and Ramos-Madrigal, J and Wales, N and Ribeiro, ER and Morrison, RR and Grimaldo, C and Prous, AP and Arriaza, B and Gilbert, MTP and de Oliveira Freitas, F and Allaby, RG}, title = {Multiproxy evidence highlights a complex evolutionary legacy of maize in South America.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1309-1313}, doi = {10.1126/science.aav0207}, pmid = {30545889}, issn = {1095-9203}, mesh = {*Biological Evolution ; *Domestication ; Genome, Plant ; Models, Biological ; Mutation ; Phylogeny ; South America ; Zea mays/*classification/*genetics ; }, abstract = {Domesticated maize evolved from wild teosinte under human influences in Mexico beginning around 9000 years before the present (yr B.P.), traversed Central America by ~7500 yr B.P., and spread into South America by ~6500 yr B.P. Landrace and archaeological maize genomes from South America suggest that the ancestral population to South American maize was brought out of the domestication center in Mexico and became isolated from the wild teosinte gene pool before traits of domesticated maize were fixed. Deeply structured lineages then evolved within South America out of this partially domesticated progenitor population. Genomic, linguistic, archaeological, and paleoecological data suggest that the southwestern Amazon was a secondary improvement center for partially domesticated maize. Multiple waves of human-mediated dispersal are responsible for the diversity and biogeography of modern South American maize.}, } @article {pmid30545888, year = {2018}, author = {Croote, D and Darmanis, S and Nadeau, KC and Quake, SR}, title = {High-affinity allergen-specific human antibodies cloned from single IgE B cell transcriptomes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1306-1309}, doi = {10.1126/science.aau2599}, pmid = {30545888}, issn = {1095-9203}, mesh = {2S Albumins, Plant/immunology ; Allergens/*immunology ; Antibody Affinity/*genetics/immunology ; Antigens, Plant/immunology ; Arachis/immunology ; Cross Reactions ; *Gene Rearrangement, B-Lymphocyte ; Glycoproteins/immunology ; Humans ; Immunoglobulin E/*genetics/immunology ; Immunoglobulin Variable Region/genetics/immunology ; Mutation ; Peanut Hypersensitivity/*immunology ; Plant Proteins/immunology ; RNA Splicing ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome ; }, abstract = {Immunoglobulin E (IgE) antibodies protect against helminth infections but can also cause life-threatening allergic reactions. Despite their role in human health, the cells that produce these antibodies are rarely observed and remain enigmatic. We isolated single IgE B cells from individuals with food allergies and used single-cell RNA sequencing to elucidate the gene expression and splicing patterns unique to these cells. We identified a surprising example of convergent evolution in which IgE antibodies underwent identical gene rearrangements in unrelated individuals. Through the acquisition of variable region mutations, these IgE antibodies gained high affinity and unexpected cross-reactivity to the clinically important peanut allergens Ara h 2 and Ara h 3. These findings provide insight into IgE B cell transcriptomics and enable biochemical dissection of this antibody class.}, } @article {pmid30545887, year = {2018}, author = {Uraguchi, D and Kuwata, K and Hijikata, Y and Yamaguchi, R and Imaizumi, H and Am, S and Rakers, C and Mori, N and Akiyama, K and Irle, S and McCourt, P and Kinoshita, T and Ooi, T and Tsuchiya, Y}, title = {A femtomolar-range suicide germination stimulant for the parasitic plant Striga hermonthica.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1301-1305}, doi = {10.1126/science.aau5445}, pmid = {30545887}, issn = {1095-9203}, mesh = {Crops, Agricultural ; Germination/*drug effects ; Herbicides/chemistry/*pharmacology ; Lactones/*metabolism ; Plant Weeds/*drug effects/physiology ; Seeds/drug effects ; Striga/*drug effects/growth & development ; }, abstract = {The parasitic plant Striga hermonthica has been causing devastating damage to the crop production in Africa. Because Striga requires host-generated strigolactones to germinate, the identification of selective and potent strigolactone agonists could help control these noxious weeds. We developed a selective agonist, sphynolactone-7, a hybrid molecule originated from chemical screening, that contains two functional modules derived from a synthetic scaffold and a core component of strigolactones. Cooperative action of these modules in the activation of a high-affinity strigolactone receptor ShHTL7 allows sphynolactone-7 to provoke Striga germination with potency in the femtomolar range. We demonstrate that sphynolactone-7 is effective for reducing Striga parasitism without impinging on host strigolactone-related processes.}, } @article {pmid30545886, year = {2018}, author = {Cheng, H and Edwards, RL and Southon, J and Matsumoto, K and Feinberg, JM and Sinha, A and Zhou, W and Li, H and Li, X and Xu, Y and Chen, S and Tan, M and Wang, Q and Wang, Y and Ning, Y}, title = {Atmospheric 14C/12C changes during the last glacial period from Hulu Cave.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1293-1297}, doi = {10.1126/science.aau0747}, pmid = {30545886}, issn = {1095-9203}, abstract = {Paired measurements of 14C/12C and 230Th ages from two Hulu Cave stalagmites complete a precise record of atmospheric 14C covering the full range of the 14C dating method (~54,000 years). Over the last glacial period, atmospheric 14C/12C ranges from values similar to modern values to values 1.70 times higher (42,000 to 39,000 years ago). The latter correspond to 14C ages 5200 years less than calibrated ages and correlate with the Laschamp geomagnetic excursion followed by Heinrich Stadial 4. Millennial-scale variations are largely attributable to Earth's magnetic field changes and in part to climate-related changes in the oceanic carbon cycle. A progressive shift to lower 14C/12C values between 25,000 and 11,000 years ago is likely related, in part, to progressively increasing ocean ventilation rates.}, } @article {pmid30545885, year = {2018}, author = {Yuan, D and Guan, Y and Chen, W and Zhao, H and Yu, S and Luo, C and Tan, Y and Xie, T and Wang, X and Sun, Z and Zhang, DH and Yang, X}, title = {Observation of the geometric phase effect in the H + HD → H2 + D reaction.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1289-1293}, doi = {10.1126/science.aav1356}, pmid = {30545885}, issn = {1095-9203}, abstract = {Theory has established the importance of geometric phase (GP) effects in the adiabatic dynamics of molecular systems with a conical intersection connecting the ground- and excited-state potential energy surfaces, but direct observation of their manifestation in chemical reactions remains a major challenge. Here, we report a high-resolution crossed molecular beams study of the H + HD → H2 + D reaction at a collision energy slightly above the conical intersection. Velocity map ion imaging revealed fast angular oscillations in product quantum state-resolved differential cross sections in the forward scattering direction for H2 products at specific rovibrational levels. The experimental results agree with adiabatic quantum dynamical calculations only when the GP effect is included.}, } @article {pmid30545884, year = {2018}, author = {Studer, S and Hansen, DA and Pianowski, ZL and Mittl, PRE and Debon, A and Guffy, SL and Der, BS and Kuhlman, B and Hilvert, D}, title = {Evolution of a highly active and enantiospecific metalloenzyme from short peptides.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1285-1288}, doi = {10.1126/science.aau3744}, pmid = {30545884}, issn = {1095-9203}, support = {R01 GM073960/GM/NIGMS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; }, mesh = {Biocatalysis ; Directed Molecular Evolution ; Enzymes/*chemistry/ultrastructure ; Esters/chemistry ; Evolution, Molecular ; Hydrolysis ; Metalloproteins/*chemistry/ultrastructure ; Oligopeptides/*chemistry ; Zinc/*chemistry ; }, abstract = {Primordial sequence signatures in modern proteins imply ancestral origins tracing back to simple peptides. Although short peptides seldom adopt unique folds, metal ions might have templated their assembly into higher-order structures in early evolution and imparted useful chemical reactivity. Recapitulating such a biogenetic scenario, we have combined design and laboratory evolution to transform a zinc-binding peptide into a globular enzyme capable of accelerating ester cleavage with exacting enantiospecificity and high catalytic efficiency (kcat/KM ~ 106 M-1 s-1). The simultaneous optimization of structure and function in a naïve peptide scaffold not only illustrates a plausible enzyme evolutionary pathway from the distant past to the present but also proffers exciting future opportunities for enzyme design and engineering.}, } @article {pmid30545883, year = {2018}, author = {Oran, D and Rodriques, SG and Gao, R and Asano, S and Skylar-Scott, MA and Chen, F and Tillberg, PW and Marblestone, AH and Boyden, ES}, title = {3D nanofabrication by volumetric deposition and controlled shrinkage of patterned scaffolds.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1281-1285}, doi = {10.1126/science.aau5119}, pmid = {30545883}, issn = {1095-9203}, support = {R01 EB024261/EB/NIBIB NIH HHS/United States ; U01 MH106011/MH/NIMH NIH HHS/United States ; DP1 NS087724/NS/NINDS NIH HHS/United States ; R01 MH103910/MH/NIMH NIH HHS/United States ; R01 DA029639/DA/NIDA NIH HHS/United States ; RM1 HG008525/HG/NHGRI NIH HHS/United States ; R24 MH106075/MH/NIMH NIH HHS/United States ; }, abstract = {Lithographic nanofabrication is often limited to successive fabrication of two-dimensional (2D) layers. We present a strategy for the direct assembly of 3D nanomaterials consisting of metals, semiconductors, and biomolecules arranged in virtually any 3D geometry. We used hydrogels as scaffolds for volumetric deposition of materials at defined points in space. We then optically patterned these scaffolds in three dimensions, attached one or more functional materials, and then shrank and dehydrated them in a controlled way to achieve nanoscale feature sizes in a solid substrate. We demonstrate that our process, Implosion Fabrication (ImpFab), can directly write highly conductive, 3D silver nanostructures within an acrylic scaffold via volumetric silver deposition. Using ImpFab, we achieve resolutions in the tens of nanometers and complex, non-self-supporting 3D geometries of interest for optical metamaterials.}, } @article {pmid30545882, year = {2018}, author = {Gotlieb, K and Lin, CY and Serbyn, M and Zhang, W and Smallwood, CL and Jozwiak, C and Eisaki, H and Hussain, Z and Vishwanath, A and Lanzara, A}, title = {Revealing hidden spin-momentum locking in a high-temperature cuprate superconductor.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1271-1275}, doi = {10.1126/science.aao0980}, pmid = {30545882}, issn = {1095-9203}, abstract = {Cuprate superconductors have long been thought of as having strong electronic correlations but negligible spin-orbit coupling. Using spin- and angle-resolved photoemission spectroscopy, we discovered that one of the most studied cuprate superconductors, Bi2212, has a nontrivial spin texture with a spin-momentum locking that circles the Brillouin zone center and a spin-layer locking that allows states of opposite spin to be localized in different parts of the unit cell. Our findings pose challenges for the vast majority of models of cuprates, such as the Hubbard model and its variants, where spin-orbit interaction has been mostly neglected, and open the intriguing question of how the high-temperature superconducting state emerges in the presence of this nontrivial spin texture.}, } @article {pmid30545881, year = {2018}, author = {, }, title = {Revealing the brain's molecular architecture.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1262-1263}, doi = {10.1126/science.362.6420.1262}, pmid = {30545881}, issn = {1095-9203}, mesh = {Brain/*growth & development/*metabolism ; Gene Expression Regulation ; Humans ; Mental Disorders/*genetics ; Transcriptome ; }, } @article {pmid30545880, year = {2018}, author = {Brockington, D and Adams, WM and Agarwal, B and Agrawal, A and Büscher, B and Chhatre, A and Duffy, R and Fletcher, R and Oldekop, JA}, title = {Working governance for working land.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1257}, doi = {10.1126/science.aav8452}, pmid = {30545880}, issn = {1095-9203}, mesh = {*Biodiversity ; *Conservation of Natural Resources ; }, } @article {pmid30545879, year = {2018}, author = {Wolf, SM and Evans, BJ}, title = {Defending the return of results and data.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1255-1256}, doi = {10.1126/science.aaw1851}, pmid = {30545879}, issn = {1095-9203}, support = {R01 HG008605/HG/NHGRI NIH HHS/United States ; }, } @article {pmid30545878, year = {2018}, author = {Khalatbari, L and Brito, JC and Ghoddousi, A and Abolghasemi, H and Breitenmoser, U and Breitenmoser-Würsten, C and Yusefi, GH and Ostrowski, S and Durant, SM}, title = {Sanctioning to extinction in Iran.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1255}, doi = {10.1126/science.aav8221}, pmid = {30545878}, issn = {1095-9203}, mesh = {*Acinonyx ; Animals ; *Endangered Species ; *Extinction, Biological ; *International Cooperation ; Iran ; }, } @article {pmid30545877, year = {2018}, author = {Golde, TE and DeKosky, ST and Galasko, D}, title = {Alzheimer's disease: The right drug, the right time.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1250-1251}, doi = {10.1126/science.aau0437}, pmid = {30545877}, issn = {1095-9203}, support = {U01 AG046139/AG/NIA NIH HHS/United States ; P50 AG047266/AG/NIA NIH HHS/United States ; P50 AG005131/AG/NIA NIH HHS/United States ; }, mesh = {Alzheimer Disease/diagnosis/*drug therapy/metabolism ; Amyloid/metabolism ; Antibodies/therapeutic use ; Biomarkers/analysis ; Clinical Trials as Topic ; Humans ; Time Factors ; Treatment Failure ; }, } @article {pmid30545876, year = {2018}, author = {Bouwmeester, H}, title = {Can witchweed be wiped out?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1248-1249}, doi = {10.1126/science.aav8482}, pmid = {30545876}, issn = {1095-9203}, mesh = {Central Nervous System Stimulants ; *Germination ; *Striga ; Suicide ; }, } @article {pmid30545875, year = {2018}, author = {Gould, HJ and Ramadani, F}, title = {Peanut allergen-specific antibodies go public.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1247-1248}, doi = {10.1126/science.aav3709}, pmid = {30545875}, issn = {1095-9203}, mesh = {*Allergens ; Arachis/*immunology ; B-Lymphocytes ; Humans ; Immunoglobulin E ; Plant Proteins ; Transcriptome ; }, } @article {pmid30545874, year = {2018}, author = {Zeder, MA}, title = {Did maize dispersal precede domestication?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1246-1247}, doi = {10.1126/science.aav7358}, pmid = {30545874}, issn = {1095-9203}, mesh = {*Domestication ; Genes, Plant ; Selection, Genetic ; South America ; Zea mays/*genetics ; }, } @article {pmid30545873, year = {2018}, author = {Long, TE and Williams, CB}, title = {Printing nanomaterials in shrinking gels.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1244-1245}, doi = {10.1126/science.aav5712}, pmid = {30545873}, issn = {1095-9203}, mesh = {*Gels ; Nanostructures ; *Printing ; }, } @article {pmid30545872, year = {2018}, author = {Crist, E}, title = {Reimagining the human.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1242-1244}, doi = {10.1126/science.aau6026}, pmid = {30545872}, issn = {1095-9203}, mesh = {*Consummatory Behavior ; *Human Activities ; Humans ; *Natural Resources ; }, } @article {pmid30545871, year = {2018}, author = {Boyd, R and Richerson, PJ and Meinzen-Dick, R and De Moor, T and Jackson, MO and Gjerde, KM and Harden-Davies, H and Frischmann, BM and Madison, MJ and Strandburg, KJ and McLean, AR and Dye, C}, title = {Tragedy revisited.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1236-1241}, doi = {10.1126/science.aaw0911}, pmid = {30545871}, issn = {1095-9203}, mesh = {Disasters/*prevention & control ; Humans ; *Natural Resources ; *Social Norms ; *Social Participation ; }, } @article {pmid30545870, year = {2018}, author = {Clery, D}, title = {Starry eyes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1230-1235}, doi = {10.1126/science.362.6420.1230}, pmid = {30545870}, issn = {1095-9203}, } @article {pmid30545869, year = {2018}, author = {Langin, K}, title = {Conferences score well on child care.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1229}, doi = {10.1126/science.362.6420.1229-b}, pmid = {30545869}, issn = {1095-9203}, mesh = {Child ; *Child Care ; Congresses as Topic ; Female ; Humans ; Male ; North America ; }, } @article {pmid30545868, year = {2018}, author = {Gibbons, A}, title = {Why modern humans have round heads.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1229}, doi = {10.1126/science.362.6420.1229-a}, pmid = {30545868}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Brain/*anatomy & histology ; *DNA, Ancient ; Head/*anatomy & histology ; Humans ; Neanderthals/*genetics ; }, } @article {pmid30545867, year = {2018}, author = {Service, RF}, title = {Bioelectronics that vanish in the body.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1228}, doi = {10.1126/science.362.6420.1228}, pmid = {30545867}, issn = {1095-9203}, mesh = {Biosensing Techniques ; *Electronics ; *Silicon ; }, } @article {pmid30545866, year = {2018}, author = {Servick, K}, title = {Human brain samples yield a genomic trove.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1227}, doi = {10.1126/science.362.6420.1227}, pmid = {30545866}, issn = {1095-9203}, mesh = {Brain/*metabolism ; DNA/genetics ; Datasets as Topic ; *Genomics ; Humans ; Mental Disorders/*genetics ; Regulatory Sequences, Nucleic Acid ; }, } @article {pmid30545865, year = {2018}, author = {Popkin, G}, title = {Space laser to map trees in 3D.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1226}, doi = {10.1126/science.362.6420.1226}, pmid = {30545865}, issn = {1095-9203}, mesh = {Biodiversity ; *Biomass ; Carbon/*analysis ; Extraterrestrial Environment ; *Forests ; *Geographic Mapping ; Satellite Imagery/*methods ; *Trees ; }, } @article {pmid30545864, year = {2018}, author = {Cohen, J}, title = {Worries about Ebola outbreak grow, despite use of vaccine.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1225}, doi = {10.1126/science.362.6420.1225}, pmid = {30545864}, issn = {1095-9203}, mesh = {Democratic Republic of the Congo/epidemiology ; Disease Outbreaks/*prevention & control ; Ebola Vaccines/*immunology ; Ebolavirus/*isolation & purification ; Hemorrhagic Fever, Ebola/*epidemiology/*prevention & control ; Humans ; }, } @article {pmid30545863, year = {2018}, author = {Cohen, J}, title = {U.N. HIV/AIDS agency assailed for culture of harassment.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1224}, doi = {10.1126/science.362.6420.1224}, pmid = {30545863}, issn = {1095-9203}, mesh = {*Acquired Immunodeficiency Syndrome ; Humans ; Sexual Harassment/*prevention & control ; United Nations/*ethics ; }, } @article {pmid30545862, year = {2018}, author = {Wadman, M and Kaiser, J}, title = {Trump officials move to limit human fetal tissue research.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1223-1224}, doi = {10.1126/science.362.6420.1223}, pmid = {30545862}, issn = {1095-9203}, mesh = {Federal Government ; Fetal Research/*ethics/*legislation & jurisprudence ; *Fetus ; Humans ; National Institutes of Health (U.S.) ; Policy ; United States ; }, } @article {pmid30545861, year = {2018}, author = {Toner, E}, title = {Ireland slashes peat power to lower emissions.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1222-1223}, doi = {10.1126/science.362.6420.1222}, pmid = {30545861}, issn = {1095-9203}, mesh = {*Fossil Fuels ; Greenhouse Effect/*prevention & control ; *Greenhouse Gases ; Ireland ; }, } @article {pmid30545860, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1218-1220}, doi = {10.1126/science.362.6420.1218}, pmid = {30545860}, issn = {1095-9203}, } @article {pmid30545859, year = {2018}, author = {Barrett, S}, title = {Choices in the climate commons.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1217}, doi = {10.1126/science.aaw2116}, pmid = {30545859}, issn = {1095-9203}, mesh = {Animals ; *Climate Change ; }, } @article {pmid30545858, year = {2018}, author = {Dzau, VJ and McNutt, M and Bai, C}, title = {Wake-up call from Hong Kong.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1215}, doi = {10.1126/science.aaw3127}, pmid = {30545858}, issn = {1095-9203}, mesh = {*CRISPR-Cas Systems ; Gene Editing/*ethics/*standards ; *Genome, Human ; Hong Kong ; Humans ; Stakeholder Participation ; }, } @article {pmid30545857, year = {2018}, author = {Wang, D and Liu, S and Warrell, J and Won, H and Shi, X and Navarro, FCP and Clarke, D and Gu, M and Emani, P and Yang, YT and Xu, M and Gandal, MJ and Lou, S and Zhang, J and Park, JJ and Yan, C and Rhie, SK and Manakongtreecheep, K and Zhou, H and Nathan, A and Peters, M and Mattei, E and Fitzgerald, D and Brunetti, T and Moore, J and Jiang, Y and Girdhar, K and Hoffman, GE and Kalayci, S and Gümüş, ZH and Crawford, GE and , and Roussos, P and Akbarian, S and Jaffe, AE and White, KP and Weng, Z and Sestan, N and Geschwind, DH and Knowles, JA and Gerstein, MB}, title = {Comprehensive functional genomic resource and integrative model for the human brain.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {}, doi = {10.1126/science.aat8464}, pmid = {30545857}, issn = {1095-9203}, support = {R01 MH093725/MH/NIMH NIH HHS/United States ; R01 MH111721/MH/NIMH NIH HHS/United States ; P50 MH096891/MH/NIMH NIH HHS/United States ; R01 MH110928/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; R21 MH109956/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; P50 MH066392/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; P50 MH084051/MH/NIMH NIH HHS/United States ; R01 MH110905/MH/NIMH NIH HHS/United States ; R01 MH110920/MH/NIMH NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; R01 MH110921/MH/NIMH NIH HHS/United States ; R01 MH105472/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 MH109677/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R21 MH105853/MH/NIMH NIH HHS/United States ; R01 MH109715/MH/NIMH NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; R01 MH110926/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/*metabolism ; Datasets as Topic ; Deep Learning ; Enhancer Elements, Genetic ; Epigenesis, Genetic ; Epigenomics ; *Gene Expression Regulation ; Gene Regulatory Networks ; Genome-Wide Association Study ; Humans ; Mental Disorders/*genetics ; Quantitative Trait Loci ; Single-Cell Analysis ; Transcriptome ; }, abstract = {Despite progress in defining genetic risk for psychiatric disorders, their molecular mechanisms remain elusive. Addressing this, the PsychENCODE Consortium has generated a comprehensive online resource for the adult brain across 1866 individuals. The PsychENCODE resource contains ~79,000 brain-active enhancers, sets of Hi-C linkages, and topologically associating domains; single-cell expression profiles for many cell types; expression quantitative-trait loci (QTLs); and further QTLs associated with chromatin, splicing, and cell-type proportions. Integration shows that varying cell-type proportions largely account for the cross-population variation in expression (with >88% reconstruction accuracy). It also allows building of a gene regulatory network, linking genome-wide association study variants to genes (e.g., 321 for schizophrenia). We embed this network into an interpretable deep-learning model, which improves disease prediction by ~6-fold versus polygenic risk scores and identifies key genes and pathways in psychiatric disorders.}, } @article {pmid30545856, year = {2018}, author = {Gandal, MJ and Zhang, P and Hadjimichael, E and Walker, RL and Chen, C and Liu, S and Won, H and van Bakel, H and Varghese, M and Wang, Y and Shieh, AW and Haney, J and Parhami, S and Belmont, J and Kim, M and Moran Losada, P and Khan, Z and Mleczko, J and Xia, Y and Dai, R and Wang, D and Yang, YT and Xu, M and Fish, K and Hof, PR and Warrell, J and Fitzgerald, D and White, K and Jaffe, AE and , and Peters, MA and Gerstein, M and Liu, C and Iakoucheva, LM and Pinto, D and Geschwind, DH}, title = {Transcriptome-wide isoform-level dysregulation in ASD, schizophrenia, and bipolar disorder.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {}, doi = {10.1126/science.aat8127}, pmid = {30545856}, issn = {1095-9203}, support = {R01 MH093725/MH/NIMH NIH HHS/United States ; P50 MH096891/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; P50 MH066392/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R01 MH100027/MH/NIMH NIH HHS/United States ; U01 MH116489/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; R01 MH110920/MH/NIMH NIH HHS/United States ; R01 MH108528/MH/NIMH NIH HHS/United States ; R21 MH104766/MH/NIMH NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; R01 MH105472/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R01 MH109885/MH/NIMH NIH HHS/United States ; U01 MH115746/MH/NIMH NIH HHS/United States ; R01 MH105524/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; P50 MH106438/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R01 MH109715/MH/NIMH NIH HHS/United States ; R01 MH110555/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; S10 OD018522/OD/NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; U01 MH116492/MH/NIMH NIH HHS/United States ; }, mesh = {Autism Spectrum Disorder/*genetics ; Bipolar Disorder/*genetics ; Brain/metabolism ; *Genetic Predisposition to Disease ; Humans ; Protein Isoforms/genetics ; *RNA Splicing ; Schizophrenia/*genetics ; Sequence Analysis, RNA ; Transcriptome ; }, abstract = {Most genetic risk for psychiatric disease lies in regulatory regions, implicating pathogenic dysregulation of gene expression and splicing. However, comprehensive assessments of transcriptomic organization in diseased brains are limited. In this work, we integrated genotypes and RNA sequencing in brain samples from 1695 individuals with autism spectrum disorder (ASD), schizophrenia, and bipolar disorder, as well as controls. More than 25% of the transcriptome exhibits differential splicing or expression, with isoform-level changes capturing the largest disease effects and genetic enrichments. Coexpression networks isolate disease-specific neuronal alterations, as well as microglial, astrocyte, and interferon-response modules defining previously unidentified neural-immune mechanisms. We integrated genetic and genomic data to perform a transcriptome-wide association study, prioritizing disease loci likely mediated by cis effects on brain expression. This transcriptome-wide characterization of the molecular pathology across three major psychiatric disorders provides a comprehensive resource for mechanistic insight and therapeutic development.}, } @article {pmid30545855, year = {2018}, author = {Zhu, Y and Sousa, AMM and Gao, T and Skarica, M and Li, M and Santpere, G and Esteller-Cucala, P and Juan, D and Ferrández-Peral, L and Gulden, FO and Yang, M and Miller, DJ and Marques-Bonet, T and Imamura Kawasawa, Y and Zhao, H and Sestan, N}, title = {Spatiotemporal transcriptomic divergence across human and macaque brain development.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {}, doi = {10.1126/science.aat8077}, pmid = {30545855}, issn = {1095-9203}, support = {U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R21 MH109956/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; R21 MH105853/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R01 MH111721/MH/NIMH NIH HHS/United States ; R01 MH110928/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; R01 MH110926/MH/NIMH NIH HHS/United States ; R01 MH110921/MH/NIMH NIH HHS/United States ; R01 MH110920/MH/NIMH NIH HHS/United States ; R01 MH110905/MH/NIMH NIH HHS/United States ; R01 MH109715/MH/NIMH NIH HHS/United States ; R01 MH109677/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; R01 MH109904/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/*genetics ; Brain/*embryology/growth & development ; *Gene Expression Regulation, Developmental ; Humans ; Macaca mulatta ; Neurogenesis/*genetics ; Prefrontal Cortex/enzymology/growth & development ; Schizophrenia/*genetics ; Transcriptome ; }, abstract = {Human nervous system development is an intricate and protracted process that requires precise spatiotemporal transcriptional regulation. We generated tissue-level and single-cell transcriptomic data from up to 16 brain regions covering prenatal and postnatal rhesus macaque development. Integrative analysis with complementary human data revealed that global intraspecies (ontogenetic) and interspecies (phylogenetic) regional transcriptomic differences exhibit concerted cup-shaped patterns, with a late fetal-to-infancy (perinatal) convergence. Prenatal neocortical transcriptomic patterns revealed transient topographic gradients, whereas postnatal patterns largely reflected functional hierarchy. Genes exhibiting heterotopic and heterochronic divergence included those transiently enriched in the prenatal prefrontal cortex or linked to autism spectrum disorder and schizophrenia. Our findings shed light on transcriptomic programs underlying the evolution of human brain development and the pathogenesis of neuropsychiatric disorders.}, } @article {pmid30545854, year = {2018}, author = {Li, M and Santpere, G and Imamura Kawasawa, Y and Evgrafov, OV and Gulden, FO and Pochareddy, S and Sunkin, SM and Li, Z and Shin, Y and Zhu, Y and Sousa, AMM and Werling, DM and Kitchen, RR and Kang, HJ and Pletikos, M and Choi, J and Muchnik, S and Xu, X and Wang, D and Lorente-Galdos, B and Liu, S and Giusti-Rodríguez, P and Won, H and de Leeuw, CA and Pardiñas, AF and , and , and , and Hu, M and Jin, F and Li, Y and Owen, MJ and O'Donovan, MC and Walters, JTR and Posthuma, D and Reimers, MA and Levitt, P and Weinberger, DR and Hyde, TM and Kleinman, JE and Geschwind, DH and Hawrylycz, MJ and State, MW and Sanders, SJ and Sullivan, PF and Gerstein, MB and Lein, ES and Knowles, JA and Sestan, N}, title = {Integrative functional genomic analysis of human brain development and neuropsychiatric risks.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {}, doi = {10.1126/science.aat7615}, pmid = {30545854}, issn = {1095-9203}, support = {RC2 MH089929/MH/NIMH NIH HHS/United States ; R01 MH111721/MH/NIMH NIH HHS/United States ; R01 MH110928/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; R21 MH109956/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R24 HD000836/HD/NICHD NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; R01 MH110905/MH/NIMH NIH HHS/United States ; R01 MH110920/MH/NIMH NIH HHS/United States ; R01 MH110921/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; RC2 MH090047/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 MH109677/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R21 MH105853/MH/NIMH NIH HHS/United States ; R01 MH109715/MH/NIMH NIH HHS/United States ; R01 MH109901/MH/NIMH NIH HHS/United States ; R01 MH110926/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; RC2 MH089921/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/*embryology/growth & development ; Epigenesis, Genetic ; Epigenomics ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Humans ; Mental Disorders/*genetics ; Nervous System Diseases/*genetics ; Neurogenesis/*genetics ; Single-Cell Analysis ; Transcriptome ; }, abstract = {To broaden our understanding of human neurodevelopment, we profiled transcriptomic and epigenomic landscapes across brain regions and/or cell types for the entire span of prenatal and postnatal development. Integrative analysis revealed temporal, regional, sex, and cell type-specific dynamics. We observed a global transcriptomic cup-shaped pattern, characterized by a late fetal transition associated with sharply decreased regional differences and changes in cellular composition and maturation, followed by a reversal in childhood-adolescence, and accompanied by epigenomic reorganizations. Analysis of gene coexpression modules revealed relationships with epigenomic regulation and neurodevelopmental processes. Genes with genetic associations to brain-based traits and neuropsychiatric disorders (including MEF2C, SATB2, SOX5, TCF4, and TSHZ3) converged in a small number of modules and distinct cell types, revealing insights into neurodevelopment and the genomic basis of neuropsychiatric risks.}, } @article {pmid30545853, year = {2018}, author = {Amiri, A and Coppola, G and Scuderi, S and Wu, F and Roychowdhury, T and Liu, F and Pochareddy, S and Shin, Y and Safi, A and Song, L and Zhu, Y and Sousa, AMM and , and Gerstein, M and Crawford, GE and Sestan, N and Abyzov, A and Vaccarino, FM}, title = {Transcriptome and epigenome landscape of human cortical development modeled in organoids.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {}, doi = {10.1126/science.aat6720}, pmid = {30545853}, issn = {1095-9203}, support = {R01 MH093725/MH/NIMH NIH HHS/United States ; R01 MH111721/MH/NIMH NIH HHS/United States ; P50 MH096891/MH/NIMH NIH HHS/United States ; R01 MH110928/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; R21 MH109956/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; P50 MH066392/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; P50 MH084051/MH/NIMH NIH HHS/United States ; R01 MH110905/MH/NIMH NIH HHS/United States ; R01 MH110920/MH/NIMH NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; R01 MH110921/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 MH109677/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R21 MH105853/MH/NIMH NIH HHS/United States ; R01 MH109715/MH/NIMH NIH HHS/United States ; R01 MH110926/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; }, mesh = {Cerebral Cortex/*embryology ; Enhancer Elements, Genetic ; *Epigenesis, Genetic ; *Gene Expression Regulation, Developmental ; Humans ; Induced Pluripotent Stem Cells/cytology ; *Models, Neurological ; Neurogenesis/*genetics ; Organoids/*embryology ; Transcriptome ; }, abstract = {Genes implicated in neuropsychiatric disorders are active in human fetal brain, yet difficult to study in a longitudinal fashion. We demonstrate that organoids from human pluripotent cells model cerebral cortical development on the molecular level before 16 weeks postconception. A multiomics analysis revealed differentially active genes and enhancers, with the greatest changes occurring at the transition from stem cells to progenitors. Networks of converging gene and enhancer modules were assembled into six and four global patterns of expression and activity across time. A pattern with progressive down-regulation was enriched with human-gained enhancers, suggesting their importance in early human brain development. A few convergent gene and enhancer modules were enriched in autism-associated genes and genomic variants in autistic children. The organoid model helps identify functional elements that may drive disease onset.}, } @article {pmid30545852, year = {2018}, author = {An, JY and Lin, K and Zhu, L and Werling, DM and Dong, S and Brand, H and Wang, HZ and Zhao, X and Schwartz, GB and Collins, RL and Currall, BB and Dastmalchi, C and Dea, J and Duhn, C and Gilson, MC and Klei, L and Liang, L and Markenscoff-Papadimitriou, E and Pochareddy, S and Ahituv, N and Buxbaum, JD and Coon, H and Daly, MJ and Kim, YS and Marth, GT and Neale, BM and Quinlan, AR and Rubenstein, JL and Sestan, N and State, MW and Willsey, AJ and Talkowski, ME and Devlin, B and Roeder, K and Sanders, SJ}, title = {Genome-wide de novo risk score implicates promoter variation in autism spectrum disorder.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {}, doi = {10.1126/science.aat6576}, pmid = {30545852}, issn = {1095-9203}, support = {R01 MH110928/MH/NIMH NIH HHS/United States ; U01 MH111661/MH/NIMH NIH HHS/United States ; R01 MH111721/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; U01 MH105575/MH/NIMH NIH HHS/United States ; R21 MH109956/MH/NIMH NIH HHS/United States ; U01 MH111658/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R24 HD000836/HD/NICHD NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; R01 HD081256/HD/NICHD NIH HHS/United States ; R01 MH110905/MH/NIMH NIH HHS/United States ; R01 MH110920/MH/NIMH NIH HHS/United States ; R01 MH110921/MH/NIMH NIH HHS/United States ; U01 MH100239/MH/NIMH NIH HHS/United States ; R01 MH094400/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 MH109677/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R21 MH105853/MH/NIMH NIH HHS/United States ; R01 MH049428/MH/NIMH NIH HHS/United States ; R01 MH109901/MH/NIMH NIH HHS/United States ; R01 MH109715/MH/NIMH NIH HHS/United States ; U01 MH111662/MH/NIMH NIH HHS/United States ; R01 MH110926/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; U01 MH111660/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R01 MH113557/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; }, mesh = {Autism Spectrum Disorder/*genetics ; Binding Sites/genetics ; Conserved Sequence ; DNA Mutational Analysis ; Genetic Loci ; Genetic Variation ; Humans ; *Mutation ; Pedigree ; Promoter Regions, Genetic/*genetics ; Risk ; Transcription Factors/metabolism ; }, abstract = {Whole-genome sequencing (WGS) has facilitated the first genome-wide evaluations of the contribution of de novo noncoding mutations to complex disorders. Using WGS, we identified 255,106 de novo mutations among sample genomes from members of 1902 quartet families in which one child, but not a sibling or their parents, was affected by autism spectrum disorder (ASD). In contrast to coding mutations, no noncoding functional annotation category, analyzed in isolation, was significantly associated with ASD. Casting noncoding variation in the context of a de novo risk score across multiple annotation categories, however, did demonstrate association with mutations localized to promoter regions. We found that the strongest driver of this promoter signal emanates from evolutionarily conserved transcription factor binding sites distal to the transcription start site. These data suggest that de novo mutations in promoter regions, characterized by evolutionary and functional signatures, contribute to ASD.}, } @article {pmid30545851, year = {2018}, author = {Rajarajan, P and Borrman, T and Liao, W and Schrode, N and Flaherty, E and Casiño, C and Powell, S and Yashaswini, C and LaMarca, EA and Kassim, B and Javidfar, B and Espeso-Gil, S and Li, A and Won, H and Geschwind, DH and Ho, SM and MacDonald, M and Hoffman, GE and Roussos, P and Zhang, B and Hahn, CG and Weng, Z and Brennand, KJ and Akbarian, S}, title = {Neuron-specific signatures in the chromosomal connectome associated with schizophrenia risk.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {}, doi = {10.1126/science.aat4311}, pmid = {30545851}, issn = {1095-9203}, support = {F30 MH113330/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; R01 MH106056/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/growth & development/metabolism ; Cells, Cultured ; Chromatin/chemistry ; Chromatin Assembly and Disassembly ; Chromosomes, Human/*chemistry ; *Connectome ; *Epigenesis, Genetic ; *Gene Expression Regulation, Developmental ; *Genetic Predisposition to Disease ; Genome, Human ; Genome-Wide Association Study ; Humans ; Male ; Neural Stem Cells/*cytology/metabolism ; Neurogenesis/*genetics ; Neuroglia/cytology ; Neurons/cytology/metabolism ; Nucleic Acid Conformation ; Protein Interaction Maps/genetics ; Proteomics ; Risk ; Schizophrenia/*genetics ; Transcription, Genetic ; Transcriptome ; }, abstract = {To explore the developmental reorganization of the three-dimensional genome of the brain in the context of neuropsychiatric disease, we monitored chromosomal conformations in differentiating neural progenitor cells. Neuronal and glial differentiation was associated with widespread developmental remodeling of the chromosomal contact map and included interactions anchored in common variant sequences that confer heritable risk for schizophrenia. We describe cell type-specific chromosomal connectomes composed of schizophrenia risk variants and their distal targets, which altogether show enrichment for genes that regulate neuronal connectivity and chromatin remodeling, and evidence for coordinated transcriptional regulation and proteomic interaction of the participating genes. Developmentally regulated chromosomal conformation changes at schizophrenia-relevant sequences disproportionally occurred in neurons, highlighting the existence of cell type-specific disease risk vulnerabilities in spatial genome organization.}, } @article {pmid30545847, year = {2019}, author = {Matharu, N and Rattanasopha, S and Tamura, S and Maliskova, L and Wang, Y and Bernard, A and Hardin, A and Eckalbar, WL and Vaisse, C and Ahituv, N}, title = {CRISPR-mediated activation of a promoter or enhancer rescues obesity caused by haploinsufficiency.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6424}, pages = {}, doi = {10.1126/science.aau0629}, pmid = {30545847}, issn = {1095-9203}, abstract = {A wide range of human diseases result from haploinsufficiency, where the function of one of the two gene copies is lost. Here, we targeted the remaining functional copy of a haploinsufficient gene using CRISPR-mediated activation (CRISPRa) in Sim1 and Mc4r heterozygous mouse models to rescue their obesity phenotype. Transgenic-based CRISPRa targeting of the Sim1 promoter or its distant hypothalamic enhancer up-regulated its expression from the endogenous functional allele in a tissue-specific manner, rescuing the obesity phenotype in Sim1 heterozygous mice. To evaluate the therapeutic potential of CRISPRa, we injected CRISPRa-recombinant adeno-associated virus into the hypothalamus, which led to reversal of the obesity phenotype in Sim1 and Mc4r haploinsufficient mice. Our results suggest that endogenous gene up-regulation could be a potential strategy to treat altered gene dosage diseases.}, } @article {pmid30545846, year = {2019}, author = {Chen, L and Lau, JA and Schwarzer, D and Meyer, J and Verma, VB and Wodtke, AM}, title = {The Sommerfeld ground-wave limit for a molecule adsorbed at a surface.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6423}, pages = {158-161}, doi = {10.1126/science.aav4278}, pmid = {30545846}, issn = {1095-9203}, abstract = {Using a mid-infrared emission spectrometer based on a superconducting nanowire single-photon detector, we observed the dynamics of vibrational energy pooling of carbon monoxide (CO) adsorbed at the surface of a sodium chloride (NaCl) crystal. After exciting a majority of the CO molecules to their first vibrationally excited state (v = 1), we observed infrared emission from states up to v = 27. Kinetic Monte Carlo simulations showed that vibrational energy collects in a few CO molecules at the expense of those up to eight lattice sites away by selective excitation of NaCl's transverse phonons. The vibrating CO molecules behave like classical oscillating dipoles, losing their energy to NaCl lattice vibrations via the electromagnetic near-field. This is analogous to Sommerfeld's description of radio transmission along Earth's surface by ground waves.}, } @article {pmid30545845, year = {2019}, author = {Itskanov, S and Park, E}, title = {Structure of the posttranslational Sec protein-translocation channel complex from yeast.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6422}, pages = {84-87}, doi = {10.1126/science.aav6740}, pmid = {30545845}, issn = {1095-9203}, abstract = {The Sec61 protein-conducting channel mediates transport of many proteins, such as secretory proteins, across the endoplasmic reticulum (ER) membrane during or after translation. Posttranslational transport is enabled by two additional membrane proteins associated with the channel, Sec63 and Sec62, but its mechanism is poorly understood. We determined a structure of the Sec complex (Sec61-Sec63-Sec71-Sec72) from Saccharomyces cerevisiae by cryo-electron microscopy (cryo-EM). The structure shows that Sec63 tightly associates with Sec61 through interactions in cytosolic, transmembrane, and ER-luminal domains, prying open Sec61's lateral gate and translocation pore and thus activating the channel for substrate engagement. Furthermore, Sec63 optimally positions binding sites for cytosolic and luminal chaperones in the complex to enable efficient polypeptide translocation. Our study provides mechanistic insights into eukaryotic posttranslational protein translocation.}, } @article {pmid30545844, year = {2019}, author = {Awasthi, A and Ramachandran, B and Ahmed, S and Benito, E and Shinoda, Y and Nitzan, N and Heukamp, A and Rannio, S and Martens, H and Barth, J and Burk, K and Wang, YT and Fischer, A and Dean, C}, title = {Synaptotagmin-3 drives AMPA receptor endocytosis, depression of synapse strength, and forgetting.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6422}, pages = {}, doi = {10.1126/science.aav1483}, pmid = {30545844}, issn = {1095-9203}, abstract = {Forgetting is important. Without it, the relative importance of acquired memories in a changing environment is lost. We discovered that synaptotagmin-3 (Syt3) localizes to postsynaptic endocytic zones and removes AMPA receptors from synaptic plasma membranes in response to stimulation. AMPA receptor internalization, long-term depression (LTD), and decay of long-term potentiation (LTP) of synaptic strength required calcium-sensing by Syt3 and were abolished through Syt3 knockout. In spatial memory tasks, mice in which Syt3 was knocked out learned normally but exhibited a lack of forgetting. Disrupting Syt3:GluA2 binding in a wild-type background mimicked the lack of LTP decay and lack of forgetting, and these effects were occluded in the Syt3 knockout background. Our findings provide evidence for a molecular mechanism in which Syt3 internalizes AMPA receptors to depress synaptic strength and promote forgetting.}, } @article {pmid30545843, year = {2018}, author = {Duffy, PB and Field, CB and Diffenbaugh, NS and Doney, SC and Dutton, Z and Goodman, S and Heinzerling, L and Hsiang, S and Lobell, DB and Mickley, LJ and Myers, S and Natali, SM and Parmesan, C and Tierney, S and Williams, AP}, title = {Strengthened scientific support for the Endangerment Finding for atmospheric greenhouse gases.}, journal = {Science (New York, N.Y.)}, volume = {}, number = {}, pages = {}, doi = {10.1126/science.aat5982}, pmid = {30545843}, issn = {1095-9203}, abstract = {We assess scientific evidence that has emerged since the U.S. Environmental Protection Agency's 2009 Endangerment Finding for six well-mixed greenhouse gases, and find that this new evidence lends increased support to the conclusion that these gases pose a danger to public health and welfare. Newly available evidence about a wide range of observed and projected impacts strengthens the association between risk of some of these impacts and anthropogenic climate change; indicates that some impacts or combinations of impacts have the potential to be more severe than previously understood; and identifies substantial risk of additional impacts through processes and pathways not considered in the endangerment finding.}, } @article {pmid30545712, year = {2018}, author = {Spiga, L and Winter, SE}, title = {Using Enteric Pathogens to Probe the Gut Microbiota.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.11.007}, pmid = {30545712}, issn = {1878-4380}, abstract = {Enteric pathogens have evolved to manipulate the interface between the host and commensal microbial communities, making these pathogenic organisms superb research tools to interrogate the function of the gut microbiota during inflammatory flares. Here, we provide an overview of conceptual insights gained from experimental infection with enteric pathogens, such as Salmonella enterica serovar Typhimurium. Metabolic pathways at the host-microbe intersection will be a particular area of focus. A better understanding of the cellular and molecular mechanisms that control host-microbe interactions during episodes of inflammation may aid in the rational design of microbiota-targeting therapies.}, } @article {pmid30545419, year = {2018}, author = {Zhang, G and Li, B and Liu, J and Luan, M and Yue, L and Jiang, XT and Yu, K and Guan, Y}, title = {The bacterial community significantly promotes cast iron corrosion in reclaimed wastewater distribution systems.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {222}, doi = {10.1186/s40168-018-0610-5}, pmid = {30545419}, issn = {2049-2618}, support = {51478238//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Currently, the effect of the bacterial community on cast iron corrosion process does not reach consensus. Moreover, some studies have produced contrasting results, suggesting that bacteria can either accelerate or inhibit corrosion.

RESULTS: The long-term effects of the bacterial community on cast iron corrosion in reclaimed wastewater distribution systems were investigated from both spatial (yellow layer vs. black layer) and temporal (1-year dynamic process) dimensions of the iron coupon-reclaimed wastewater microcosm using high-throughput sequencing and flow cytometry approaches. Cast iron coupons in the NONdisinfection and UVdisinfection reactors suffered more severe corrosion than did those in the NaClOdisinfection reactor. The bacterial community significantly promoted cast iron corrosion, which was quantified for the first time in the practical reclaimed wastewater and found to account for at least 30.5% ± 9.7% of the total weight loss. The partition of yellow and black layers of cast iron corrosion provided more accurate information on morphology and crystal structures for corrosion scales. The black layer was dense, and the particles looked fusiform, while the yellow layer was loose, and the particles were ellipse or spherical. Goethite was the predominant crystalline phase in black layers, while corrosion products mainly existed as an amorphous phase in yellow layers. The bacterial community compositions of black layers were distinctly separated from yellow layers regardless of disinfection methods. The NONdisinfection and UVdisinfection reactors had a more similar microbial composition and variation tendency for the same layer type than did the NaClOdisinfection reactor. Biofilm development can be divided into the initial start-up stage, mid-term development stage, and terminal stable stage. In total, 12 potential functional genera were selected to establish a cycle model for Fe, N, and S metabolism. Desulfovibrio was considered to accelerate the transfer of Fe0 to Fe2+ and speed up weight loss.

CONCLUSION: The long-term effect of disinfection processes on corrosion behaviors of cast iron in reclaimed wastewater distribution systems and the hidden mechanisms were deciphered for the first time. This study established a cycle model for Fe, N, and S metabolism that involved 12 functional genera and discovered the significant contribution of Desulfovibrio in promoting corrosion.}, } @article {pmid30545417, year = {2018}, author = {Jacquiod, S and Nunes, I and Brejnrod, A and Hansen, MA and Holm, PE and Johansen, A and Brandt, KK and Priemé, A and Sørensen, SJ}, title = {Long-term soil metal exposure impaired temporal variation in microbial metatranscriptomes and enriched active phages.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {223}, doi = {10.1186/s40168-018-0606-1}, pmid = {30545417}, issn = {2049-2618}, support = {289949//FP7 People: Marie-Curie Actions/ ; }, abstract = {BACKGROUND: It remains unclear whether adaptation and changes in diversity associated to a long-term perturbation are sufficient to ensure functional resilience of soil microbial communities. We used RNA-based approaches (16S rRNA gene transcript amplicon coupled to shotgun mRNA sequencing) to study the legacy effects of a century-long soil copper (Cu) pollution on microbial activity and composition, as well as its effect on the capacity of the microbial community to react to temporal fluctuations.

RESULTS: Despite evidence of microbial adaptation (e.g., iron homeostasis and avoidance/resistance strategies), increased heterogeneity and richness loss in transcribed gene pools were observed with increasing soil Cu, together with an unexpected predominance of phage mRNA signatures. Apparently, phage activation was either triggered directly by Cu, or indirectly via enhanced expression of DNA repair/SOS response systems in Cu-exposed bacteria. Even though total soil carbon and nitrogen had accumulated with increasing Cu, a reduction in temporally induced mRNA functions was observed. Microbial temporal response groups (TRGs, groups of microbes with a specific temporal response) were heavily affected by Cu, both in abundance and phylogenetic composition.

CONCLUSION: Altogether, results point toward a Cu-mediated "decoupling" between environmental fluctuations and microbial activity, where Cu-exposed microbes stopped fulfilling their expected contributions to soil functioning relative to the control. Nevertheless, some functions remained active in February despite Cu, concomitant with an increase in phage mRNA signatures, highlighting that somehow, microbial activity is still happening under these adverse conditions.}, } @article {pmid30545414, year = {2018}, author = {Ballouk, MA and Dashash, M}, title = {The gingival health status of 8-12 year-old children in Damascus city in Syria during the Syrian Crisis: a cross-sectional epidemiological oral health survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {887}, doi = {10.1186/s13104-018-3998-x}, pmid = {30545414}, issn = {1756-0500}, abstract = {OBJECTIVE: The aim of this study was to assess the current gingival health status in children aged 8-12 years in Damascus city. No contemporary data was available with an immense need for studies evaluating the gingival health status in Syrian children, especially under the current circumstances of the Syrian crisis.

RESULTS: The study followed the school-based health survey model using stratified random cluster sampling. A total of 1500 children were clinically examined. The mean PI was at (1.39 ± 0.57) and the mean GI was at (1.12 ± 0.46). Of the total sample, (97.93%) had gingivitis. There is a statistically significant relationship between the used indices means and the children's distribution as to the city's localities. Also, there is a statistically significant relationship between the used indices means and the children's gender. Gingival health was seen to be better and plaque accumulations were less in females. The gingival health status is moderate and is within the acceptable ranges while the plaque accumulations are right above moderate. Still, gingivitis prevalence is high and special care as well as developing and implementing advanced preventive programmes are highly needed.}, } @article {pmid30545411, year = {2018}, author = {James, SN and Lane, CA and Parker, TD and Lu, K and Collins, JD and Murray-Smith, H and Byford, M and Wong, A and Keshavan, A and Buchanan, S and Keuss, SE and Kuh, D and Fox, NC and Schott, JM and Richards, M}, title = {Using a birth cohort to study brain health and preclinical dementia: recruitment and participation rates in Insight 46.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {885}, doi = {10.1186/s13104-018-3995-0}, pmid = {30545411}, issn = {1756-0500}, support = {109/Z/15/Z//Wellcome Trust/United Kingdom ; MC_UU_12019/1//Medical Research Council/United Kingdom ; ARUK-PG2017-1946//Alzheimer's Research UK/ ; ARUK-PG2014-1946//Alzheimer's Research UK/ ; //Wellcome Trust/United Kingdom ; 200//Wellcome Trust/United Kingdom ; }, abstract = {OBJECTIVE: Identifying and recruiting people with early pre-symptomatic Alzheimer's disease to neuroimaging research studies is increasingly important. The extent to which results of these studies can be generalised depends on the recruitment and representativeness of the participants involved. We now report the recruitment and participation patterns from a neuroscience sub-study of the MRC National Survey of Health and Development, "Insight 46". This study aimed to recruit 500 participants for extensive clinical and neuropsychological testing, and neuroimaging. We investigate how sociodemographic factors, health conditions and health-related behaviours predict participation at different levels of recruitment.

RESULTS: We met our target recruitment (n = 502). Higher educational attainment and non-manual socio-economic position (SEP) were consistent predictors of recruitment. Health-related variables were also predictive at every level of recruitment; in particular higher cognition, not smoking and better self-rating health. Sex and APOE-e4 status were not predictors of participation at any level. Whilst recruitment targets were met, individuals with lower SEP, lower cognition, and more health problems are under-represented in Insight 46. Understanding the factors that influence recruitment are important when interpreting results; for Insight 46 it is likely that health-related outcomes and life course risks will under-estimate those seen in the general population.}, } @article {pmid30545410, year = {2018}, author = {Sung, EJ and Shears, SB}, title = {A genome-wide dsRNA library screen for Drosophila genes that regulate the GBP/phospholipase C signaling axis that links inflammation to aging.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {884}, doi = {10.1186/s13104-018-3996-z}, pmid = {30545410}, issn = {1756-0500}, support = {R01 GM067761/GM/NIGMS NIH HHS/United States ; Z01 ES080046/ES/NIEHS NIH HHS/United States ; }, abstract = {OBJECTIVE: Invertebrates are productive models for understanding how inflammation, metabolism and aging are intertwined. We have deployed a dsRNA library screen to search for genes in Drosophila melanogaster-and hence identify human orthologs-that encode participants in a G-protein coupled, Ca2+-signaling pathway that regulates inflammation, metabolism and lifespan.

RESULTS: We analyzed receptor-dependent, phospholipase C/Ca2+ signaling responses to the growth-blocking peptide (GBP) cytokine in Drosophila S3 cells plated in 384-well plates containing dsRNAs that target approximately 14,000 Drosophila genes. We used Z-scores of < - 3 or > + 3 to define gene hits. Filtering of 'housekeeping' genes from these hits yielded a total of 82 and 61 Drosophila genes that either down-regulate or up-regulate Ca2+-signaling, respectively; representatives from these two groups were validated. Human orthologs of our hits may be modulators of Ca2+ signaling in general, as well as being candidates for acting in molecular pathways that interconnect aging and inflammation.}, } @article {pmid30545405, year = {2018}, author = {Zhan, J and Liang, Y and Liu, D and Ma, X and Li, P and Liu, C and Liu, X and Wang, P and Zhou, Z}, title = {Antibiotics may increase triazine herbicide exposure risk via disturbing gut microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {224}, doi = {10.1186/s40168-018-0602-5}, pmid = {30545405}, issn = {2049-2618}, support = {21337005//National Natural Science Foundation of China/ ; 21677175//National Natural Science Foundation of China/ ; 2017LX001//Chinese Universities Scientific Fund/ ; }, abstract = {BACKGROUND: Antibiotics are commonly used worldwide, and pesticide is a kind of xenobiotic to which humans are frequently exposed. The interactive impact of antibiotics on pesticides has rarely been studied. We aim to investigate the effects of antibiotics on the pesticide exposure risk and whether gut microbiota altered by antibiotics has an influence on pesticide bioavailability. Furthermore, we explored the mechanisms of gut microbiota affecting the fate of pesticides in the host.

RESULTS: The oral bioavailability of triazine herbicides significantly increased in the rats treated with ampicillin or antibiotic cocktails. The antibiotic-altered gut microbiota directly influenced the increased pesticide bioavailability through downregulating hepatic metabolic enzyme gene expression and upregulating intestinal absorption-related proteins.

CONCLUSIONS: Antibiotics could increase the pesticide bioavailability and thereby may increase the pesticide exposure risk. The antibiotic-altered gut microbiota that could alter the hepatic metabolic enzyme gene expression and intestinal absorption-related proteome was a critical cause of the increased bioavailability. This study revealed an undiscovered potential health impact of antibiotics and reminded people to consider the co-exposed xenobiotics when taking antibiotics.}, } @article {pmid30545404, year = {2018}, author = {Mwang'onde, BJ and Chacha, MJ and Nkwengulila, G}, title = {The status and health burden of neurocysticercosis in Mbulu district, northern Tanzania.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {890}, doi = {10.1186/s13104-018-3999-9}, pmid = {30545404}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {OBJECTIVE: The objective of this study was to assess the extent and health burden of neurocysticercosis in the general community of the Mbulu district, northern Tanzania. About 1051 randomly select participants were screened for human cysticercosis. The Cysticercus Western Blot IgG and Computed Tomography scan were used to detect infection by cysticerci. The DALYs was used to assess the community's health burden vis-a-vis neurocysticercosis.

RESULTS: The sero-prevalence of HCC was 16.27%. About 76% of 25 selected human cysticercosis sero-positives had neurocysticercosis suggestive lesions on CT scan and 74% had history of epilepsy. Epilepsy caused 2.8 years of life lost and 2.2 healthy years of life lost due to disability per 1000 person-years in Mbulu. The average DALYs imposed due to neurocysticercosis and epilepsy were 3.0 and 3.9 per 1000 person-years, respectively. Neurocysticercosis is a serious public health concern in northern Tanzania.}, } @article {pmid30545402, year = {2018}, author = {Egbe, TO and Badjang, TG and Tchounzou, R and Egbe, EN and Ngowe, MN}, title = {Uterine fibroids in pregnancy: prevalence, clinical presentation, associated factors and outcomes at the Limbe and Buea Regional Hospitals, Cameroon: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {889}, doi = {10.1186/s13104-018-4007-0}, pmid = {30545402}, issn = {1756-0500}, abstract = {OBJECTIVES: Uterine fibroids are common among the black race and associated with adverse outcomes in pregnancy. The aim of this study was to determine the prevalence, clinical presentation and maternal and foetal outcomes of birth among pregnant women with leiomyoma in two secondary care hospitals in Limbe and Buea, Cameroon.

RESULTS: The prevalence of fibroid in pregnancy was 16.7%. Respondents with leiomyoma were older than those without (p < 0.001) and of low parity (p = 0.02). Acute abdominal pain, (OR 3.8; 95% CI 1.4-9.9, p = 0.007), vaginal bleeding (OR 5.2; 95% CI 1.6-16.3, p = 0.004) were clinical presentation of leiomyoma in pregnancy. Cesarean birth (OR 4.5; 95% CI 1.4-13.6, p = 0.008), low Apgar score, (OR 6.0; 95% CI 1.9-19.1, p = 0.002), and postpartum hemorrhage (OR 4.7; 95% CI 1.7-13.2, p = 0.003) were adverse outcomes recorded.}, } @article {pmid30545401, year = {2018}, author = {Forbes, JD and Chen, CY and Knox, NC and Marrie, RA and El-Gabalawy, H and de Kievit, T and Alfa, M and Bernstein, CN and Van Domselaar, G}, title = {A comparative study of the gut microbiota in immune-mediated inflammatory diseases-does a common dysbiosis exist?.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {221}, doi = {10.1186/s40168-018-0603-4}, pmid = {30545401}, issn = {2049-2618}, abstract = {BACKGROUND: Immune-mediated inflammatory disease (IMID) represents a substantial health concern. It is widely recognized that IMID patients are at a higher risk for developing secondary inflammation-related conditions. While an ambiguous etiology is common to all IMIDs, in recent years, considerable knowledge has emerged regarding the plausible role of the gut microbiome in IMIDs. This study used 16S rRNA gene amplicon sequencing to compare the gut microbiota of patients with Crohn's disease (CD; N = 20), ulcerative colitis (UC; N = 19), multiple sclerosis (MS; N = 19), and rheumatoid arthritis (RA; N = 21) versus healthy controls (HC; N = 23). Biological replicates were collected from participants within a 2-month interval. This study aimed to identify common (or unique) taxonomic biomarkers of IMIDs using both differential abundance testing and a machine learning approach.

RESULTS: Significant microbial community differences between cohorts were observed (pseudo F = 4.56; p = 0.01). Richness and diversity were significantly different between cohorts (pFDR < 0.001) and were lowest in CD while highest in HC. Abundances of Actinomyces, Eggerthella, Clostridium III, Faecalicoccus, and Streptococcus (pFDR < 0.001) were significantly higher in all disease cohorts relative to HC, whereas significantly lower abundances were observed for Gemmiger, Lachnospira, and Sporobacter (pFDR < 0.001). Several taxa were found to be differentially abundant in IMIDs versus HC including significantly higher abundances of Intestinibacter in CD, Bifidobacterium in UC, and unclassified Erysipelotrichaceae in MS and significantly lower abundances of Coprococcus in CD, Dialister in MS, and Roseburia in RA. A machine learning approach to classify disease versus HC was highest for CD (AUC = 0.93 and AUC = 0.95 for OTU and genus features, respectively) followed by MS, RA, and UC. Gemmiger and Faecalicoccus were identified as important features for classification of subjects to CD and HC. In general, features identified by differential abundance testing were consistent with machine learning feature importance.

CONCLUSIONS: This study identified several gut microbial taxa with differential abundance patterns common to IMIDs. We also found differentially abundant taxa between IMIDs. These taxa may serve as biomarkers for the detection and diagnosis of IMIDs and suggest there may be a common component to IMID etiology.}, } @article {pmid30545400, year = {2018}, author = {Muvunyi, CM and Harelimana, JD and Sebatunzi, OR and Atmaprakash, AC and Seruyange, E and Masaisa, F and Manzi, O and Nyundo, M and Hategekimana, T}, title = {Hepatitis B vaccination coverage among healthcare workers at a tertiary hospital in Rwanda.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {886}, doi = {10.1186/s13104-018-4002-5}, pmid = {30545400}, issn = {1756-0500}, support = {Seed Grant//Center for Teaching and Learning, Boise State University (US)/ ; }, abstract = {OBJECTIVE: We evaluated post-vaccination immunity status and describe potential risk factors associated with the lack of response among healthcare workers (HCWs) at a tertiary care hospital in Kigali, Rwanda.

RESULTS: Of 373 HCWs, 291 (78.2%) were female and 81 (21.8%) were male. The mean age of the study participants was 40.2 years (standard deviation [SD], 7.7 years), within a range of 24-41 years. Participants' mean BMI was 25.4 ± 6.6 kg/m2, with more than half of patients (60.3%) being overweight. 96% received all three doses of vaccination. A total of 36 participants (9.6%) were considered non responders as they did not develop a sufficient anti-HBs response post vaccination. The anti-HBs response was significantly higher in females when compared to males (p = 0.02). Interestingly, there was no significant association between decline in antibody levels with age (p = 0.242) and BMI (p = 0.516) of the participants. The anti-HBs titers were similar in the group of participants who had received two doses and those who had received three doses of the HBV vaccination. Overall the findings of our study provide a basis for testing for anti-HBs in all HCWs post vaccination in Rwanda.}, } @article {pmid30545390, year = {2018}, author = {Biratu, AK and Wakgari, N and Jikamo, B}, title = {Magnitude of fetal macrosomia and its associated factors at public health institutions of Hawassa city, southern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {888}, doi = {10.1186/s13104-018-4005-2}, pmid = {30545390}, issn = {1756-0500}, abstract = {OBJECTIVES: This study aimed to determine the magnitude of fetal macrosomia and associated factors at public health institutions of Hawassa city, southern Ethiopia.

RESULTS: In this study, the magnitude of fetal macrosomia found to be 11.86%. Being a male (AOR = 2.2, 95% CI 1.1-4.2), ≥ 37 weeks gestational age (AOR = 6.0, 95% CI 3.1-11.1) and having previous history of fetal macrosomia (AOR = 14.5, 95% CI 7.2-29.2) had a higher odds of fetal macrosomia. Moreover, the magnitude of fetal macrosomia is found be in the global range. Sex of the child, previous history of fetal macrosomia and gestational age were significantly associated with fetal macrosomia. The obstetric care providers should assess all pregnant women for history of fetal macrosomia which would help them to be prepared for the managements of maternal and perinatal complications.}, } @article {pmid30545356, year = {2018}, author = {Herron, MD and Zamani-Dahaj, SA and Ratcliff, WC}, title = {Trait heritability in major transitions.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {145}, doi = {10.1186/s12915-018-0612-6}, pmid = {30545356}, issn = {1741-7007}, abstract = {BACKGROUND: Increases in biological complexity and the origins of life's hierarchical organization are described by the "major transitions" framework. A crucial component of this paradigm is that after the transition in complexity or organization, adaptation occurs primarily at the level of the new, higher-level unit. For collective-level adaptations to occur, though, collective-level traits-properties of the group, such as collective size-must be heritable. Since collective-level trait values are functions of lower-level trait values, collective-level heritability is related to particle-level heritability. However, the nature of this relationship has rarely been explored in the context of major transitions.

RESULTS: We examine relationships between particle-level heritability and collective-level heritability for several functions that express collective-level trait values in terms of particle-level trait values. For clonal populations, when a collective-level trait value is a linear function of particle-level trait values and the number of particles per collective is fixed, the heritability of a collective-level trait is never less than that of the corresponding particle-level trait and is higher under most conditions. For more complicated functions, collective-level heritability is higher under most conditions, but can be lower when the environment experienced by collectives is heterogeneous. Within-genotype variation in collective size reduces collective-level heritability, but it can still exceed particle-level heritability when phenotypic variance among particles within collectives is large. These results hold for a diverse sample of biologically relevant traits.

CONCLUSIONS: Rather than being an impediment to major transitions, we show that, under a wide range of conditions, the heritability of collective-level traits is actually higher than that of the corresponding particle-level traits. High levels of collective-level trait heritability thus arise "for free," with important implications not only for major transitions but for multilevel selection in general.}, } @article {pmid30545311, year = {2018}, author = {Huang, J and Luo, X and Huang, M and Liu, G and You, W and Ke, C}, title = {Identification and characteristics of muscle growth-related microRNA in the Pacific abalone, Haliotis discus hannai.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {915}, doi = {10.1186/s12864-018-5347-9}, pmid = {30545311}, issn = {1471-2164}, support = {No.U1605213//National Natural Science Foundation of China/ ; 31872564//National Natural Science Foundation of China/ ; No. CARS-49//Earmarked Fund for Modern Agro-industry Technology Research System/ ; No. 2016GGH4513//Key S & T Program of Shandong Province/ ; No. 18GZY012HJ02//Xiamen Southern Oceanographic Center/ ; }, abstract = {BACKGROUND: The Pacific abalone, Haliotis discus hannai, is the most important cultivated abalone in China. Improving abalone muscle growth and increasing the rate of growth are important genetic improvement programs in this industry. MicroRNAs are important small noncoding RNA molecules that regulate post-transcription gene expression. However, no miRNAs have been reported to regulate muscle growth in H. discus hannai.

RESULTS: we profiled six small RNA libraries for three large abalone individuals (L_HD group) and three small individuals (S_HD group) using RNA sequencing technology. A total of 205 miRNAs, including 200 novel and 5 known miRNAs, were identified. In the L_HD group, 3 miRNAs were up-regulated and 7 were down-regulated compared to the S_HD specimens. Bioinformatics analysis of miRNA target genes revealed that miRNAs participated in the regulation of cellular metabolic processes, the regulation of biological processes, the Wnt signaling pathway, ECM-receptor interaction, and the MAPK signaling pathway, which are associated with regulating growth. Bone morphogenetic protein 7 (BMP7) was verified as a target gene of hdh-miR-1984 by a luciferase reporter assay and we examined the expression pattern in different developmental stages.

CONCLUSION: This is the first study to demonstrate that miRNAs are related to the muscle growth of H. discus hannai. This information could be used to study the mechanisms of abalone muscle growth. These DE-miRNAs may be useful as molecular markers for functional genomics and breeding research in abalone and closely related species.}, } @article {pmid30545307, year = {2018}, author = {Yang, Y and Cui, B and Tan, Z and Song, B and Cao, H and Zong, C}, title = {RNA sequencing and anthocyanin synthesis-related genes expression analyses in white-fruited Vaccinium uliginosum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {930}, doi = {10.1186/s12864-018-5351-0}, pmid = {30545307}, issn = {1471-2164}, support = {31460504//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Vaccinium uliginosum (Ericaceae) is an important wild berry having high economic value. The white-fruited V. uliginosum variety found in the wild lacks anthocyanin and bears silvery white fruits. Hence, it is a good resource for investigating the mechanism of fruit color development. This study aimed to verify the differences in the expression levels of some structural genes and transcription factors affecting the anthocyanin biosynthesis pathway by conducting high-throughput transcriptome sequencing and real-time PCR analysis by using the ripening fruits of V. uliginosum and the white-fruited variety.

RESULTS: We annotated 42,837 unigenes. Of the 325 differentially expressed genes, 41 were up-regulated and 284 were down-regulated. Further, 11 structural genes of the flavonoid pathway were up-regulated, whereas two were down-regulated. Of the seven genes encoding transcription factors, five were up-regulated and two were down-regulated. The structural genes VuCHS, VuF3'H, VuFHT, VuDFR, VuANS, VuANR, and VuUFGT and the transcription factors VubHLH92, VuMYB6, VuMYBPA1, VuMYB11, and VuMYB12 were significantly down-regulated. However, the expression of only VuMYB6 and VuMYBPA1 rapidly increased during the last two stages of V. uliginosum when the fruit was ripening, consistent with anthocyanin accumulation.

CONCLUSIONS: VuMYB6 was annotated as MYB1 by the BLAST tool. Thus, the white fruit color in the V. uliginosum variant can be attributed to the down-regulation of transcription factors VuMYB1 and VuMYBPA1, which leads to the down-regulation of structural genes associated with the anthocyanin synthesis pathway.}, } @article {pmid30545302, year = {2018}, author = {Cáceres, A and González, JR}, title = {When pitch adds to volume: coregulation of transcript diversity predicts gene function.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {926}, doi = {10.1186/s12864-018-5263-z}, pmid = {30545302}, issn = {1471-2164}, support = {BCV-2016-3-0002//Red Española de Supercomputación/ ; MTM2015-68140-R//Ministerio de Economía e Innovación/ ; }, abstract = {BACKGROUND: Genes corregulate their overall transcript volumes to perform their physiological functions. However, it is unknown if they additionally coregulate their transcript diversities. We studied the reliability, consistency and functional associations of co-splicing correlations of genes of interest, across two independent studies, multiple tissues and two statistical methods. We thoroughly investigated the reproducibility of co-splicing correlations of APP, the candidate gene of Azheimer's disease (AD). We then studied how co-splicing correlations in different tissues contributed to predict functional interactions of three other genes and finally computed co-splicing frequency for 17 thousand genes across 52 human tissues.

RESULTS: We replicated co-splicing correlations between APP and 5 AD-related genes and reproduced expected enrichment of APP co-splicing in synaptic vesicle cycle and proteosome pathways. We observed novel associations for tissue vulnerability to disease with enrichment in APP co-splicing, co-expression and epistasis in AD. APP co-splicing was the strongest predictor and replicated between studies. We confirmed known gene interactions of PRPF8 and GRIA1 in testis and brain cortex, and observed a novel interaction of FGFR2, in breast and prostate, modulated by cancer risk-variants. We produced a co-splicing map across 52 human tissues to help predict the function of over 17 thousand genes.

CONCLUSIONS: We show that coregulation of transcript diversities provides novel biological insights in gene physiology and helps to interpret GWAS results. Co-splicing correlations are reliable and frequent and should be further pursued to help predict gene function. Our results additionally support current AD interventions aiming at the ubiquitin proteosome pathway but unveil the need to consider transcript diversity in addition to volume to assess treatment response and susceptibility to the disease.}, } @article {pmid30545300, year = {2018}, author = {Juanchich, A and Hennequet-Antier, C and Cabau, C and Le Bihan-Duval, E and Duclos, MJ and Mignon-Grasteau, S and Narcy, A}, title = {Functional genomics of the digestive tract in broilers.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {928}, doi = {10.1186/s12864-018-5344-z}, pmid = {30545300}, issn = {1471-2164}, abstract = {BACKGROUND: The sustainability of poultry farming relies on the development of more efficient and autonomous production systems in terms of feed supply. This implies a better integration of adaptive traits in breeding programs, including digestive efficiency, in order to favor the use of a wider variety of feedstuffs. The aim of the project was to improve the understanding of genes involved in digestive functions by characterizing the transcriptome of different sections of the digestive tract: the junction between the proventriculus and the gizzard, the gizzard, the gastroduodenal junction, and the jejunum.

RESULTS: Total RNA from the four tissues were sequenced on a HiSeq2500 for six 23-day-old chickens from a second generation (F2) cross between two lines that were divergent for their digestive efficiency (D+/D-). Bioinformatics and biostatistics analyses of the RNA-seq data showed a total of 11,040 differentially expressed transcripts between the four tissues. In total, seven clusters of genes with markedly different expression profiles were identified. Functional analysis on gene groups was performed using "Gene Ontology" and semantic similarity. It showed a significant enrichment of body immune defenses in the jejunum, and an enrichment of transcriptional activity in the gizzard. Moreover, an interesting enrichment for neurohormonal control of muscle contraction was found for the two gizzard's junctions.

CONCLUSION: This analysis allows us to draw the first molecular portrait of the different sections of the digestive tract, which will serve as a basis for future studies on the genetic and physiological control of the response of the animal to feed variations.}, } @article {pmid30545299, year = {2018}, author = {Zhang, Y and Zhou, Y and Sun, G and Li, K and Li, Z and Su, A and Liu, X and Li, G and Jiang, R and Han, R and Tian, Y and Kang, X and Yan, F}, title = {Transcriptome profile in bursa of Fabricius reveals potential mode for stress-influenced immune function in chicken stress model.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {918}, doi = {10.1186/s12864-018-5333-2}, pmid = {30545299}, issn = {1471-2164}, support = {162300410141//Natural Science Foundation of Henan Province/ ; 14A230018//Key scientific research project plan of Henan Province colleges and universities/ ; 17A230015//Key scientific research project plan of Henan Province colleges and universities/ ; 162300410172//Science and Technology Planning Project of Henan Province/ ; IRT16R23//Program for Innovation Research Team of Ministry of Education/ ; }, abstract = {BACKGROUND: The molecular mechanisms underlying stress-influenced immune function of chicken (Gallus Gallus) are not clear. The stress models can be established effectively by feeding chickens corticosterone (CORT) hormone. The bursa of Fabricius is a unique central immune organ of birds. RNA-Seq technology was used to investigate differences in the expression profiles of immune-related genes and associated pathways in the bursa of Fabricius to clarify molecular mechanisms. The aim of this study was to broaden the understanding of the stress-influenced immune function in chickens.

RESULTS: Differentially expressed genes (DEGs) in the bursa of Fabricius between experimental group (basal diet with added CORT 30 mg/kg; C_B group) and control group (basal diet; B_B group) were identified by using RNA-seq technology. In total, we found 1434 significant DEGs (SDEGs), which included 199 upregulated and 1235 downregulated genes in the C_B group compared with the B_B group. The immune system process GO term was the top significantly GO term, including MYD88, TLR4, IL15, VEGFA gene and so on. The cytokine-cytokine receptor interaction pathway and the Toll-like receptor signaling pathway were the key pathways affected by stress. The protein-protein interaction (PPI) analysis of the SDEGs showed that VEGFA, MyD88 and IL15 were hub genes and module analysis showed that MYD88, TLR4 and VEGFA play important roles in response to stress.

CONCLUSION: This study showed that the VEGFA and ILs (such as IL15) via the cytokine-cytokine receptor interaction pathway, MYD88 and TLR4 via the Toll-like receptor signaling pathway may play important roles in the regulation of immune function under stress condition with CORT administration. The results of this study provide a reference for further studies of the molecular mechanisms of stress-influenced immune function.}, } @article {pmid30545298, year = {2018}, author = {He, Y and Ma, Y and Du, Y and Shen, S}, title = {Differential gene expression for carotenoid biosynthesis in a green alga Ulva prolifera based on transcriptome analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {916}, doi = {10.1186/s12864-018-5337-y}, pmid = {30545298}, issn = {1471-2164}, support = {2016YFC1402102//National Key R&D Program of China/ ; 2016YFC1402104//National Key R&D Program of China/ ; 41276134//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Carotenoids are widely distributed in plants and algae, and their biosynthesis has attracted widespread interest. Carotenoid-related research has mostly focused on model species, and there is a lack of data on the carotenoid biosynthetic pathway in U. prolifera that is the main species leading to green tide, a harmful plague of floating green algae.

RESULTS: The carotenoid content of U. prolifera samples, that is the main species leading to green tide, a harmful plague of floating green algae at different temperatures revealed that its terpenoid was highest in the samples subjected to high temperature at 28 °C (H), followed by the samples subjected to low temperature at 12 °C (L). Its terpenoid was lowest in the samples subjected to medium temperature at 20 °C (M). We conducted transcriptome sequencing (148.5 million raw reads and 49,676 unigenes in total) of samples that were subjected to different temperatures to study the carotenoid biosynthesis of U. prolifera. There were 1125-3164 significant differentially expressed genes between L, M and H incubation temperatures, of which 11-672 genes were upregulated and 453-3102 genes were downregulated. A total of 3164 genes were significantly differentially expressed between H and M, of which 62 genes were upregulated and 3102 genes were downregulated. A total of 2669 significant differentially expressed genes were observed between L and H, of which 11 genes were upregulated and 2658 genes were downregulated. A total of 13 genes were identified to be involved in carotenoid biosynthesis in U. prolifera, and the expression levels of the majority were highest at H and lowest at M of incubation temperature. Both the carotenoid concentrations and the expression of the analysed genes were lowest in the normal temperature group, while low temperature and high temperature seemed to activate the biosynthesis of carotenoids in U. prolifera.

CONCLUSIONS: In this study, transcriptome sequencing provided critical information for understanding the accumulation of carotenoids and will serve as an important reference for the study of other metabolic pathways in U. prolifera.}, } @article {pmid30545297, year = {2018}, author = {Xu, Z and Che, T and Li, F and Tian, K and Zhu, Q and Mishra, SK and Dai, Y and Li, M and Li, D}, title = {The temporal expression patterns of brain transcriptome during chicken development and ageing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {917}, doi = {10.1186/s12864-018-5301-x}, pmid = {30545297}, issn = {1471-2164}, support = {161026//Fok Ying Tong Education Foundation/ ; 02920400//The program from Sichuan Agricultural University/ ; }, abstract = {BACKGROUND: The transcriptional profiles of mammals during brain development and ageing have been characterized. However the global expression patterns of transcriptome in the chicken brain have not been explored. Here, we systematically investigated the temporal expression profiles of lncRNAs and mRNAs across 8 stages (including 3 embryonic stages, 2 growth stages and 3 adult stages) in the female chicken cerebrum.

RESULTS: We identified 39,907 putative lncRNAs and 14,558 mRNAs, investigated the temporal expression patterns by tracking a set of age-dependent genes and predicted potential biological functions of lncRNAs based on co-expression network. The results showed that genes with functions in development, synapses and axons exhibited a progressive decay; genes related to immune response were up-regulated with age.

CONCLUSIONS: These results may reflect changes in the regulation of transcriptional networks and provide non-coding RNA gene candidates for further studies and would contribute to a comprehensive understanding of the molecular mechanisms of chicken development and may provide insights or deeper understanding regarding the regulatory mechanisms of age-dependent protein coding and non-protein coding genes in chicken. In addition, as the chicken is an important model organism bridging the evolutionary gap between mammals and other vertebrates, these high resolution data may provide a novel evidence to improve our comprehensive understanding of the brain transcriptome during vertebrate evolution.}, } @article {pmid30545296, year = {2018}, author = {Schmidt, MA and Herman, EM}, title = {Characterization and functional biology of the soybean aleurone layer.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {354}, doi = {10.1186/s12870-018-1579-8}, pmid = {30545296}, issn = {1471-2229}, mesh = {Cotyledon/metabolism/physiology/ultrastructure ; Electrophoresis, Polyacrylamide Gel ; Endosperm/metabolism/physiology/ultrastructure ; Gene Expression Regulation, Plant ; Isoelectric Focusing ; Metabolome ; Microscopy, Electron, Transmission ; Plant Proteins/isolation & purification/*metabolism/physiology ; Soybeans/*metabolism/physiology/ultrastructure ; Stress, Physiological ; }, abstract = {BACKGROUND: Soybean is a globally important oil seed crop. Both the high protein and oil content of soybean seeds make this crop a lucrative commodity. As in higher eukaryotic species with available genomes, the functional annotation of most of soybean's genes still remains to be investigated. A major hurdle in the functional genomics of soybean is a rapid method to test gene constructs before embarking on stable transformation experiments.

RESULTS: In this paper we describe the morphology and composition of the persistent single-cell aleurone layer that derives from the endosperm of developing soybean seeds. Its composition compared to cotyledonary tissue indicates the aleurone layer plays a role in both abiotic and biotic stress. The potential utility as the aleurone layer as a transient expression system in soybean was shown. As a near transparent single-cell layer it can be used as a transient expression system to study transgene expression and inter- and intra-cellular targeting as it is amenable to microscopic techniques.

CONCLUSION: The transparent single cell aleurone layer was shown to be compositionally comparable to cotyledonary tissue in soybean with an enrichment in oxidative response proteins and shown to be a potential transient expression platform.}, } @article {pmid30545295, year = {2018}, author = {Huang, J and Li, Y}, title = {Rumen methanogen and protozoal communities of Tibetan sheep and Gansu Alpine Finewool sheep grazing on the Qinghai-Tibetan Plateau, China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {212}, doi = {10.1186/s12866-018-1351-0}, pmid = {30545295}, issn = {1471-2180}, support = {GAU-XKJS-2018-046//Discipline construction fund project of Gansu Agricultural University/ ; }, abstract = {BACKGROUND: Tibetan sheep (TS) and Gansu Alpine Finewool sheep (GS) are both important plateau sheep raised and fed on the harsh Qinghai-Tibetan Plateau, China. Rumen methanogen and protozoal communities of plateau sheep are affected by their hosts and living environments, and play important roles in ruminant nutrition and greenhouse gas production. However, the characteristics, differences, and associations of these communities remain largely uncharacterized.

RESULTS: The rumen methanogen and protozoal communities of plateau sheep were investigated by 16S/18S rRNA gene clone libraries. The predominant methanogen order in both sheep species was Methanobacteriales followed by Methanomassiliicoccales, which is consistent with those seen in global ruminants. However, the most dominant species was Methanobrevibacter millerae rather than Methanobrevibacter gottschalkii seen in most ruminants. Compared with GS and other ruminants, TS have more exclusive operational taxonomic units and a lower proportion (64.5%) of Methanobrevibacter. The protozoa were divided into Entodiniomorphida and Vestibuliferida, including nine genera and 15 species. The proportion of holotrich protozoa was much lower (1.1%) in TS than ordinary sheep. The most predominant genus was Entodinium (70.0%) in TS and Enoploplastron (48.8%) in GS, while the most common species was Entodinium furca monolobum (43.9%) and Enoploplastron triloricatum (45.0%) in TS and GS, respectively; Entodinium longinucleatum (22.8%) was only observed in TS. LIBSHUFF analysis indicated that the methanogen communities of TS were significantly different from those of GS, but no significant differences were found in protozoal communities.

CONCLUSION: Plateau sheep have coevolved with unique rumen methanogen and protozoal communities to adapt to harsh plateau environments. Moreover, the host appears to have a greater influence on rumen methanogen communities than on rumen protozoal communities. The observed associations of methanogens and protozoa, together with the findings of previous studies on methane emissions from ruminant livestock, revealed that the lower proportion of Methanobrevibacter and holotrich protozoa may be responsible for the lower methane emission of TS. These findings facilitate our understanding of the rumen microbial ecosystem in plateau sheep, and could help the development of new strategies to manipulate rumen microbes to improve productivity and reduce the emission of greenhouse gases.}, } @article {pmid30545294, year = {2018}, author = {Hashimoto, Y and Kurushima, J and Nomura, T and Tanimoto, K and Tamai, K and Yanagisawa, H and Shirabe, K and Ike, Y and Tomita, H}, title = {Dissemination and genetic analysis of the stealthy vanB gene clusters of Enterococcus faecium clinical isolates in Japan.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {213}, doi = {10.1186/s12866-018-1342-1}, pmid = {30545294}, issn = {1471-2180}, support = {AMED//Ministry of Health, Labour and Welfare/ ; H27-Shokuhin-Ippan-008//Ministry of Health, Labour and Welfare/ ; H30-Shokuhin-Ippan-006//Ministry of Health, Labour and Welfare/ ; Young Scientists (B)25870116//Ministry of Education, Culture, Sports, Science and Technology/ ; }, abstract = {BACKGROUND: VanB-type vancomycin (VAN) resistance gene clusters confer VAN resistances on Enterococcus spp. over a wide range of MIC levels (MIC = 4-1000 mg/L). However, the epidemiology and the molecular characteristics of the VAN susceptible VanB-type Enterococcus still remain unclear.

RESULTS: We characterized 19 isolates of VanB-type Enterococcus faecium that might colonize in the gut and were not phenotypically resistant to VAN (MIC = 3 mg/L). They were obtained from two hospitals in Japan between 2009 and 2010. These isolates had the identical vanB gene cluster and showed same multilocus sequence typing (MLST) (ST78) and the highly related profiles in pulsed-field gel electrophoresis (PFGE). The vanB gene cluster was located on a plasmid, and was transferable to E. faecium and E. faecalis. Notably, from these VanB-type VREs, VAN resistant (MIC≥16 mg/L) mutants could appear at a frequency of 10- 6-10- 7/parent cell in vitro. Most of these revertants acquired mutations in the vanSB gene, while the remainder of the revertants might have other mutations outside of the vanB gene cluster. All of the revertants we tested showed increases in the VAN-dependent expression of the vanB gene cluster, suggesting that the mutations affected the transcriptional activity and increased the VAN resistance. Targeted mutagenesis revealed that three unique nucleotide substitutions in the vanB gene cluster of these strains attenuated VAN resistance.

CONCLUSIONS: In summary, this study indicated that stealthy VanB-type E. faecium strains that have the potential ability to become resistance to VAN could exist in clinical settings.}, } @article {pmid30545293, year = {2018}, author = {Zhang, F and Bai, B and Xu, GJ and Lin, ZW and Li, GQ and Chen, Z and Cheng, H and Sun, X and Wang, HY and Chen, YW and Zheng, JX and Deng, QW and Yu, ZJ}, title = {Eravacycline activity against clinical S. aureus isolates from China: in vitro activity, MLST profiles and heteroresistance.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {211}, doi = {10.1186/s12866-018-1349-7}, pmid = {30545293}, issn = {1471-2180}, support = {No.81170370, NO.81601797//National Natural Science Foundation of China/ ; JCYJ20170307153714512, JCYJ20170307153919735 and JCYJ20170412143551332//Science, Technology, and Innovation Commission of Shenzhen Municipality of basic research funds/ ; SZFZ2017063, SZXJ2017032; SZFZ2017036;No. 201601058//Shenzhen Health and Family Planning Commission/ ; B2017019; 2014A031313718//provincial medical funds of Guangdong/ ; No. 2016010; No. 2017013; No. 2017015; No. 2017026;No. 2017027//Sanming Project of Medicine in Shenzhen; the Shenzhen Nanshan District Scientific Research Program of the People's Republic of China/ ; }, abstract = {BACKGROUND: Mortality rates for patients with Staphylococcus aureus (S. aureus) infections have improved only modestly in recent decades and S. aureus infections remain a major clinical challenge This study investigated the in vitro antimicrobial activity of erevacycline (erava) against clinical S. aureus isolates from China, as well as the heteroresistance frequency of erava and sequence types (STs) represented in the sample.

RESULTS: A sample of 328 non-duplicate clinical S. aureus isolates, including 138 methecillin-resistant (MRSA) and 190 methecillin-sensitive (MSSA) isolates, were collected retrospectively in China. Erava exhibited excellent in vitro activity (MIC50 ≤ 0.25 mg/L) against MRSA and MSSA, including isolates harboring Tet specific resistance genes. The frequency of erava heteroresistance in MSSA with erava MICs = 0.5 mg/L was 13.79% (4/29); no MRSA with erava MICs ≤0.5 mg/L exhibited heteroresistance. Heteroresistance- derived clones had no 30S ribosome subunit mutations, but their erava MICs (range, 1-4 mg/L) were suppressed dramatically in the presence of efflux protein inhibitors.

CONCLUSIONS: Conclusively, erava exhibited excellent in vitro activity against S. aureus, however hints of erava heteroresistance risk and MIC creep were detected, particularly among MSSA with MICs of 0.5 mg/L.}, } @article {pmid30545292, year = {2018}, author = {Zheng, H and Zhong, Z and Shi, M and Zhang, L and Lin, L and Hong, Y and Fang, T and Zhu, Y and Guo, J and Zhang, L and Fang, J and Lin, H and Norvienyeku, J and Chen, X and Lu, G and Hu, H and Wang, Z}, title = {Comparative genomic analysis revealed rapid differentiation in the pathogenicity-related gene repertoires between Pyricularia oryzae and Pyricularia penniseti isolated from a Pennisetum grass.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {927}, doi = {10.1186/s12864-018-5222-8}, pmid = {30545292}, issn = {1471-2164}, support = {31770156//Natural Science Foundations of China/ ; SKB2017002//State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops/ ; }, abstract = {BACKGROUND: A number of Pyricularia species are known to infect different grass species. In the case of Pyricularia oryzae (syn. Magnaporthe oryzae), distinct populations are known to be adapted to a wide variety of grass hosts, including rice, wheat and many other grasses. The genome sizes of Pyricularia species are typical for filamentous ascomycete fungi [~ 40 Mbp for P. oryzae, and ~ 45 Mbp for P. grisea]. Genome plasticity, mediated in part by deletions promoted by recombination between repetitive elements [Genome Res 26:1091-1100, 2016, Nat Rev Microbiol 10:417-430,2012] and transposable elements [Annu Rev Phytopathol 55:483-503,2017] contributes to host adaptation. Therefore, comparisons of genome structure of individual species will provide insight into the evolution of host specificity. However, except for the P. oryzae subgroup, little is known about the gene content or genome organization of other Pyricularia species, such as those infecting Pennisetum grasses.

RESULTS: Here, we report the genome sequence of P. penniseti strain P1609 isolated from a Pennisetum grass (JUJUNCAO) using PacBio SMRT sequencing technology. Phylogenomic analysis of 28 Magnaporthales species and 5 non-Magnaporthales species indicated that P1609 belongs to a Pyricularia subclade, which is genetically distant from P. oryzae. Comparative genomic analysis revealed that the pathogenicity-related gene repertoires had diverged between P1609 and the P. oryzae strain 70-15, including the known avirulence genes, other putative secreted proteins, as well as some other predicted Pathogen-Host Interaction (PHI) genes. Genomic sequence comparison also identified many genomic rearrangements relative to P. oryzae.

CONCLUSION: Our results suggested that the genomic sequence of the P. penniseti P1609 could be a useful resource for the genetic study of the Pennisetum-infecting Pyricularia species and provide new insight into evolution of pathogen genomes during host adaptation.}, } @article {pmid30545291, year = {2018}, author = {Schumacher, DI and Lütkenhaus, R and Altegoer, F and Teichert, I and Kück, U and Nowrousian, M}, title = {The transcription factor PRO44 and the histone chaperone ASF1 regulate distinct aspects of multicellular development in the filamentous fungus Sordaria macrospora.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {112}, doi = {10.1186/s12863-018-0702-z}, pmid = {30545291}, issn = {1471-2156}, support = {NO407/5-1//Deutsche Forschungsgemeinschaft/ ; KU517/16-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Fungal fruiting bodies are complex three-dimensional structures that are formed to protect and disperse the sexual spores. Their morphogenesis requires the concerted action of numerous genes; however, at the molecular level, the spatio-temporal sequence of events leading to the mature fruiting body is largely unknown. In previous studies, the transcription factor gene pro44 and the histone chaperone gene asf1 were shown to be essential for fruiting body formation in the ascomycete Sordaria macrospora. Both PRO44 and ASF1 are predicted to act on the regulation of gene expression in the nucleus, and mutants in both genes are blocked at the same stage of development. Thus, we hypothesized that PRO44 and ASF1 might be involved in similar aspects of transcriptional regulation. In this study, we characterized their roles in fruiting body development in more detail.

RESULTS: The PRO44 protein forms homodimers, localizes to the nucleus, and is strongly expressed in the outer layers of the developing young fruiting body. Analysis of single and double mutants of asf1 and three other chromatin modifier genes, cac2, crc1, and rtt106, showed that only asf1 is essential for fruiting body formation whereas cac2 and rtt106 might have redundant functions in this process. RNA-seq analysis revealed distinct roles for asf1 and pro44 in sexual development, with asf1 acting as a suppressor of weakly expressed genes during morphogenesis. This is most likely not due to global mislocalization of nucleosomes as micrococcal nuclease-sequencing did not reveal differences in nucleosome spacing and positioning around transcriptional start sites between Δasf1 and the wild type. However, bisulfite sequencing revealed a decrease in DNA methylation in Δasf1, which might be a reason for the observed changes in gene expression. Transcriptome analysis of gene expression in young fruiting bodies showed that pro44 is required for correct expression of genes involved in extracellular metabolism. Deletion of the putative transcription factor gene asm2, which is downregulated in young fruiting bodies of Δpro44, results in defects during ascospore maturation.

CONCLUSIONS: In summary, the results indicate distinct roles for the transcription factor PRO44 and the histone chaperone ASF1 in the regulation of sexual development in fungi.}, } @article {pmid30545290, year = {2018}, author = {Zhong, Y and Xu, D and Hebelstrup, KH and Yang, D and Cai, J and Wang, X and Zhou, Q and Cao, W and Dai, T and Jiang, D}, title = {Nitrogen topdressing timing modifies free amino acids profiles and storage protein gene expression in wheat grain.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {353}, doi = {10.1186/s12870-018-1563-3}, pmid = {30545290}, issn = {1471-2229}, support = {31325020, 31401326, 31471445//National Natural Science Foundation of China/ ; CARS-03//China Agriculture Research System/ ; JCIC-MCP//Jiangsu Collaborative Innovation Center for Modern Crop Production/ ; 20140039//National Non-profit Program by Ministry of Agriculture/ ; }, mesh = {Amino Acids/analysis/*metabolism ; Edible Grain/chemistry/*metabolism ; Endosperm/chemistry/metabolism ; Gene Expression Regulation, Plant/drug effects ; Nitrogen/administration & dosage/*metabolism ; Plant Leaves/metabolism ; Plant Proteins/*metabolism ; Real-Time Polymerase Chain Reaction ; Triticum/*metabolism ; }, abstract = {BACKGROUND: Nitrogen is one basic element of amino acids and grain protein in wheat. In field experiments, wheat plants were subjected to different timing of nitrogen topdressing treatments: at the stages of emergence of the top fifth leaf (TL5), top third leaf (TL3) and top first leaf (TL1) to test the regulatory effects of nitrogen topdressing timing on grain protein quality. The underlying mechanisms were elucidated by clarifying the relationship between proteolysis in vegetative organs and accumulation of amino acids in the endosperm cavity, conversion of amino acids, and storage protein synthesis in endosperm of wheat grain.

RESULTS: Delayed nitrogen topdressing up-regulated gene expression related to nitrogen metabolism and protease synthesis in the flag leaf, followed by more free amino acids being transported to both the cavity and the endosperm from 7 days after anthesis (DAA) to 13 DAA in TL1. TL1 enhanced the conversion between free amino acids in endosperm and upregulated the expression of genes encoding high molecular weight (HMW) and low molecular weight (LMW) subunits and protein disulfide isomerases-like (PDIL) proteins, indicating that the synthesis and folding of glutenin were enhanched by delayed nitrogen topdressing. As a consequense, the content of glutenin macropolymers (GMP) and glutenin increased with delaying nitrogen topdressing.

CONCLUSIONS: The results highlight the relationship between nitrogen remobilization and final grain protein production and suggest that the nitrogen remobilization processes could be a potential target for improving the quality of wheat grain. Additionally, specific gene expression related to nitrogen topdressing was identified, which conferred more detailed insights into underlying mechanism on the modification protein quality.}, } @article {pmid30545289, year = {2018}, author = {Wnętrzak, M and Błażej, P and Mackiewicz, D and Mackiewicz, P}, title = {The optimality of the standard genetic code assessed by an eight-objective evolutionary algorithm.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {192}, doi = {10.1186/s12862-018-1304-0}, pmid = {30545289}, issn = {1471-2148}, mesh = {*Algorithms ; Amino Acids/genetics ; Codon/genetics ; Discriminant Analysis ; *Evolution, Molecular ; *Genetic Code ; Models, Genetic ; Operator Regions, Genetic/genetics ; }, abstract = {BACKGROUND: The standard genetic code (SGC) is a unique set of rules which assign amino acids to codons. Similar amino acids tend to have similar codons indicating that the code evolved to minimize the costs of amino acid replacements in proteins, caused by mutations or translational errors. However, if such optimization in fact occurred, many different properties of amino acids must have been taken into account during the code evolution. Therefore, this problem can be reformulated as a multi-objective optimization task, in which the selection constraints are represented by measures based on various amino acid properties.

RESULTS: To study the optimality of the SGC we applied a multi-objective evolutionary algorithm and we used the representatives of eight clusters, which grouped over 500 indices describing various physicochemical properties of amino acids. Thanks to that we avoided an arbitrary choice of amino acid features as optimization criteria. As a consequence, we were able to conduct a more general study on the properties of the SGC than the ones presented so far in other papers on this topic. We considered two models of the genetic code, one preserving the characteristic codon blocks structure of the SGC and the other without this restriction. The results revealed that the SGC could be significantly improved in terms of error minimization, hereby it is not fully optimized. Its structure differs significantly from the structure of the codes optimized to minimize the costs of amino acid replacements. On the other hand, using newly defined quality measures that placed the SGC in the global space of theoretical genetic codes, we showed that the SGC is definitely closer to the codes that minimize the costs of amino acids replacements than those maximizing them.

CONCLUSIONS: The standard genetic code represents most likely only partially optimized systems, which emerged under the influence of many different factors. Our findings can be useful to researchers involved in modifying the genetic code of the living organisms and designing artificial ones.}, } @article {pmid30545288, year = {2018}, author = {Wang, P and Shi, S and Ma, J and Song, H and Zhang, Y and Gao, C and Zhao, C and Zhao, S and Hou, L and Lopez-Baltazar, J and Fan, S and Xia, H and Wang, X}, title = {Global Methylome and gene expression analysis during early Peanut pod development.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {352}, doi = {10.1186/s12870-018-1546-4}, pmid = {30545288}, issn = {1471-2229}, support = {31500217, 31500257, 31471526//National Natural Science Foundation of China/ ; 2016LZGC025//Shandong provincial crop elite variety development project/ ; CXGC2018E17//Agricultural scientific and technological innovation project of Shandong Academy of Agricultural Sciences/ ; }, mesh = {Arachis/genetics/*growth & development/metabolism ; Chromosome Mapping ; DNA Methylation/*genetics/physiology ; DNA, Plant/genetics/metabolism ; Flowers/genetics/growth & development/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/genetics/metabolism ; RNA, Small Interfering/genetics/metabolism ; }, abstract = {BACKGROUND: Early peanut pod development is an important process of peanut reproductive development. Modes of DNA methylation during early peanut pod development are still unclear, possibly because its allotetraploid genome may cause difficulty for the methylome analysis.

RESULTS: To investigate the functions of the dynamic DNA methylation during the early development of the peanut pod, global methylome and gene expression analyses were carried out by Illumina high throughput sequencing. A novel mapping strategy of reads was developed and used for methylome and gene expression analysis. Differentially methylated genes, such as nodulin, cell number regulator-like protein, and senescence-associated genes, were identified during the early developmental stages of the peanut pod. The expression levels of gibberellin-related genes changed during this period of pod development. From the stage one (S1) gynophore to the stage two (S2) gynophore, the expression levels of two key methyltransferase genes, DRM2 and MET1, were up-regulated, which may lead to global DNA methylation changes between these two stages. The differentially methylated and expressed genes identified in the S1, S2, and stage 3 (S3) gynophore are involved in different biological processes such as stem cell fate determination, response to red, blue, and UV light, post-embryonic morphogenesis, and auxin biosynthesis. The expression levels of many genes were co-related by their DNA methylation levels. In addition, our results showed that the abundance of some 24-nucleotide siRNAs and miRNAs were positively associated with DNA methylation levels of their target loci in peanut pods.

CONCLUSION: A novel mapping strategy of reads was described and verified in this study. Our results suggest that the methylated modes of the S1, S2, and S3 gynophore are different. The methylation changes that were identified during early peanut pod development provide useful information for understanding the roles of epigenetic regulation in peanut pod development.}, } @article {pmid30545287, year = {2018}, author = {Gold, MEL and Watanabe, A}, title = {Flightless birds are not neuroanatomical analogs of non-avian dinosaurs.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {190}, doi = {10.1186/s12862-018-1312-0}, pmid = {30545287}, issn = {1471-2148}, mesh = {Anatomic Landmarks ; Animals ; Birds/*anatomy & histology/classification ; Brain/*anatomy & histology ; Dinosaurs/*anatomy & histology ; Discriminant Analysis ; Fossils ; *Neuroanatomy ; Phylogeny ; Principal Component Analysis ; Time Factors ; }, abstract = {BACKGROUND: In comparative neurobiology, major transitions in behavior are thought to be associated with proportional size changes in brain regions. Bird-line theropod dinosaurs underwent a drastic locomotory shift from terrestrial to volant forms, accompanied by a suite of well-documented postcranial adaptations. To elucidate the potential impact of this locomotor shift on neuroanatomy, we first tested for a correlation between loss of flight in extant birds and whether the brain morphology of these birds resembles that of their flightless, non-avian dinosaurian ancestors. We constructed virtual endocasts of the braincase for 80 individuals of non-avian and avian theropods, including 25 flying and 19 flightless species of crown group birds. The endocasts were analyzed using a three-dimensional (3-D) geometric morphometric approach to assess changes in brain shape along the dinosaur-bird transition and secondary losses of flight in crown-group birds (Aves).

RESULTS: While non-avian dinosaurs and crown-group birds are clearly distinct in endocranial shape, volant and flightless birds overlap considerably in brain morphology. Phylogenetically informed analyses show that locomotory mode does not significantly account for neuroanatomical variation in crown-group birds. Linear discriminant analysis (LDA) also indicates poor predictive power of neuroanatomical shape for inferring locomotory mode. Given current sampling, Archaeopteryx, typically considered the oldest known bird, is inferred to be terrestrial based on its endocranial morphology.

CONCLUSION: The results demonstrate that loss of flight does not correlate with an appreciable amount of neuroanatomical changes across Aves, but rather is partially constrained due to phylogenetic inertia, evident from sister taxa having similarly shaped endocasts. Although the present study does not explicitly test whether endocranial changes along the dinosaur-bird transition are due to the acquisition of powered flight, the prominent relative expansion of the cerebrum, in areas associated with flight-related cognitive capacity, suggests that the acquisition of flight may have been an important initial driver of brain shape evolution in theropods.}, } @article {pmid30545286, year = {2018}, author = {Mu, Y and Wu, X and Hao, Z}, title = {Comparative evaluation of mesenchymal stromal cells from umbilical cord and amniotic membrane in xeno-free conditions.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {27}, doi = {10.1186/s12860-018-0178-8}, pmid = {30545286}, issn = {1471-2121}, support = {81860157//National Natural Science Foundation of China/ ; 2017MS0314//Natural Science Foundation of Inner Mongolia/ ; }, abstract = {BACKGROUND: Within the past years, umbilical cord (UC) and amniotic membrane (AM) expanded in human platelet lysate (PL) have been found to become increasingly candidate of mesenchymal stromal cells (MSCs) in preclinical and clinical studies. Different sources of MSCs have different properties, and lead to different therapeutic applications. However, the similarity and differences between the AMMSCs and UCMSCs in PL remain unclear.

RESULTS: In this study, we conduct a direct head-to-head comparison with regard to biological characteristics (morphology, immunophenotype, self-renewal capacity, and trilineage differentiation potential) and immunosuppression effects of AMMSCs and UCMSCs expanded in PL. Our results indicated that AMMSCs showed similar morphology, immunophenotype, proliferative capacity and colony efficiency with UCMSCs. Moreover, no significantly differences in osteogenic, chondrogenic and adipogenic differentiation potential were observed between the two types of cells. However, AMMSCs exhibited higher PGE2 expression and IDO activity compared with UCMSCs when primed by IFN-γ and (or) TNF-α induction, and AMMSCs showed a higher inhibitory effect on PBMCs proliferation than UCMSCs.

CONCLUSION: The results suggest that AMMSCs expanded in PL showed similar morphology, immunophenotype, self-renewal capacity, and trilineage differentiation potential with UCMSCs. However, AMMSCs possessed superior immunosuppression effects in comparison with UCMSCs. These results suggest that AMMSCs in PL might be more suitable than UCMSCs for treatment of immune diseases. This work provides a novel insight into choosing the appropriate source of MSCs for treatment of immune diseases.}, } @article {pmid30545285, year = {2018}, author = {Costa, RA and Martins, RST and Capilla, E and Anjos, L and Power, DM}, title = {Vertebrate SLRP family evolution and the subfunctionalization of osteoglycin gene duplicates in teleost fish.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {191}, doi = {10.1186/s12862-018-1310-2}, pmid = {30545285}, issn = {1471-2148}, mesh = {Adipocytes/cytology/metabolism ; Animals ; Cell Differentiation/genetics ; Cells, Cultured ; Conserved Sequence ; *Evolution, Molecular ; Gene Expression Profiling ; *Genes, Duplicate ; Genetic Linkage ; Genome ; Intercellular Signaling Peptides and Proteins/*genetics/metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Monocytes/cytology/metabolism ; *Multigene Family ; Phylogeny ; Promoter Regions, Genetic ; Sea Bream/*genetics ; Sequence Alignment ; Small Leucine-Rich Proteoglycans/*genetics/metabolism ; Synteny/genetics ; }, abstract = {BACKGROUND: Osteoglycin (OGN, a.k.a. mimecan) belongs to cluster III of the small leucine-rich proteoglycans (SLRP) of the extracellular matrix (ECM). In vertebrates OGN is a characteristic ECM protein of bone. In the present study we explore the evolution of SLRP III and OGN in teleosts that have a skeleton adapted to an aquatic environment.

RESULTS: The SLRP gene family has been conserved since the separation of chondrichthyes and osteichthyes. Few gene duplicates of the SLRP III family exist even in the teleosts that experienced a specific whole genome duplication. One exception is ogn for which duplicate copies were identified in fish genomes. The ogn promoter sequence and in vitro mesenchymal stem cell (MSC) cultures suggest the duplicate ogn genes acquired divergent functions. In gilthead sea bream (Sparus aurata) ogn1 was up-regulated during osteoblast and myocyte differentiation in vitro, while ogn2 was severely down-regulated during bone-derived MSCs differentiation into adipocytes in vitro.

CONCLUSIONS: Overall, the phylogenetic analysis indicates that the SLRP III family in vertebrates has been under conservative evolutionary pressure. The retention of the ogn gene duplicates in teleosts was linked with the acquisition of different functions. The acquisition by OGN of functions other than that of a bone ECM protein occurred early in the vertebrate lineage.}, } @article {pmid30545284, year = {2018}, author = {Mongiardino Koch, N and Coppard, SE and Lessios, HA and Briggs, DEG and Mooi, R and Rouse, GW}, title = {A phylogenomic resolution of the sea urchin tree of life.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {189}, doi = {10.1186/s12862-018-1300-4}, pmid = {30545284}, issn = {1471-2148}, mesh = {Animals ; *Genomics ; Kelp ; Likelihood Functions ; *Phylogeny ; Sea Urchins/anatomy & histology/*classification/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: Echinoidea is a clade of marine animals including sea urchins, heart urchins, sand dollars and sea biscuits. Found in benthic habitats across all latitudes, echinoids are key components of marine communities such as coral reefs and kelp forests. A little over 1000 species inhabit the oceans today, a diversity that traces its roots back at least to the Permian. Although much effort has been devoted to elucidating the echinoid tree of life using a variety of morphological data, molecular attempts have relied on only a handful of genes. Both of these approaches have had limited success at resolving the deepest nodes of the tree, and their disagreement over the positions of a number of clades remains unresolved.

RESULTS: We performed de novo sequencing and assembly of 17 transcriptomes to complement available genomic resources of sea urchins and produce the first phylogenomic analysis of the clade. Multiple methods of probabilistic inference recovered identical topologies, with virtually all nodes showing maximum support. In contrast, the coalescent-based method ASTRAL-II resolved one node differently, a result apparently driven by gene tree error induced by evolutionary rate heterogeneity. Regardless of the method employed, our phylogenetic structure deviates from the currently accepted classification of echinoids, with neither Acroechinoidea (all euechinoids except echinothurioids), nor Clypeasteroida (sand dollars and sea biscuits) being monophyletic as currently defined. We show that phylogenetic signal for novel resolutions of these lineages is strong and distributed throughout the genome, and fail to recover systematic biases as drivers of our results.

CONCLUSIONS: Our investigation substantially augments the molecular resources available for sea urchins, providing the first transcriptomes for many of its main lineages. Using this expanded genomic dataset, we resolve the position of several clades in agreement with early molecular analyses but in disagreement with morphological data. Our efforts settle multiple phylogenetic uncertainties, including the position of the enigmatic deep-sea echinothurioids and the identity of the sister clade to sand dollars. We offer a detailed assessment of evolutionary scenarios that could reconcile our findings with morphological evidence, opening up new lines of research into the development and evolutionary history of this ancient clade.}, } @article {pmid30544159, year = {2018}, author = {Pedrinho, A and Mendes, LW and Merloti, LF and da Fonseca, MC and Cannavan, FS and Tsai, SM}, title = {Forest-to-pasture conversion and recovery based on assessment of microbial communities in Eastern Amazon Rainforest.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy236}, pmid = {30544159}, issn = {1574-6941}, abstract = {Amazon rainforest has been subjected to particularly high rates of deforestation caused mainly by the expansion of cattle pasture and agriculture. A commonly observed response to land-use change is a negative impact on biodiversity of plant and animal species. However, its effect on the soil microbial community and ecosystem functioning is still poorly understood. Here, we used DNA metagenomic sequencing approach to investigate the impact of land-use change on soil microbial community composition and its potential functions in three land-use systems (primary forest, pasture, and secondary forest) in the Amazon region. In general, the microbial community structure was influenced by changes in soil physicochemical properties. Aluminum and water holding capacity significantly correlated to overall community structure and most of microbial phyla. Taxonomic changes were followed by potential functional changes in the soil microbial community, with pasture presenting the most distinct profile in comparison with other sites. Although taxonomic structure was very distinct between sites, we observed a recovery of the potential functions in secondary forest after pasture abandonment. Our findings elucidate a significant shift in belowground microbial taxonomic and potential functional diversity following natural forest re-establishment and have implications for ecological restoration programs in tropical and sub-tropical ecosystems.}, } @article {pmid30544151, year = {2018}, author = {Jaffe, AL and Castelle, CJ and Dupont, CL and Banfield, JF}, title = {Lateral gene transfer shapes the distribution of RuBisCO among Candidate Phyla Radiation bacteria and DPANN archaea.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy234}, pmid = {30544151}, issn = {1537-1719}, abstract = {Ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) is considered to be the most abundant enzyme on Earth. Despite this, its full diversity and distribution across the domains of life remain to be determined. Here, we leverage a large set of bacterial, archaeal, and viral genomes recovered from the environment to expand our understanding of existing RuBisCO diversity and the evolutionary processes responsible for its distribution. Specifically, we report a new type of RuBisCO present in Candidate Phyla Radiation (CPR) bacteria that is related to the archaeal Form III enzyme and contains the amino acid residues necessary for carboxylase activity. Genome-level metabolic analyses supported the inference that these RuBisCO function in a CO2-incorporating pathway that consumes nucleotides. Importantly, some Gottesmanbacteria (CPR) also encode a phosphoribulokinase that may augment carbon metabolism through a partial Calvin-Benson-Bassham Cycle. Based on the scattered distribution of RuBisCO and its discordant evolutionary history, we conclude that this enzyme has been extensively laterally transferred across the CPR bacteria and DPANN archaea. We also report RuBisCO-like proteins in phage genomes from diverse environments. These sequences cluster with proteins in the Beckwithbacteria (CPR), implicating phage as a possible mechanism of RuBisCO transfer. Finally, we synthesize our metabolic and evolutionary analyses to suggest that lateral gene transfer of RuBisCO may have facilitated major shifts in carbon metabolism in several important bacterial and archaeal lineages.}, } @article {pmid30543510, year = {2018}, author = {Volokhov, DV and Batac, F and Gao, Y and Miller, M and Chizhikov, VE}, title = {Mycoplasma enhydrae sp. nov. isolated from southern sea otters (Enhydra lutris nereis).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003144}, pmid = {30543510}, issn = {1466-5034}, abstract = {Five Mycoplasma strains have been isolated from the oropharynx of southern sea otters (Enhydra lutris nereis) from the Central California Coast, USA. These strains were phenotypically and genetically characterized and compared to other established Mycoplasma species. All five strains hydrolysed arginine but not urea, but did not produce acid from glucose, and all were isolated and propagated under anaerobic and aerobic atmospheric conditions at +35-37 ˚C using either SP4 or PPLO medium supplemented with arginine. Colonies on solid medium showed a typical fried-egg appearance and transmission electron microscopy revealed a typical mycoplasma cellular morphology. Molecular characterization included assessment of the following genetic loci: 16S rRNA, 16S-23S rRNA ITS, rpoB, rpoC, polC, topIIA, tufB, arcA and smc. Complete 16S rRNA gene sequence analysis indicated that these strains were most closely related to Mycoplasma phocicerebrale, and to Mycoplasma arginini, Mycoplasma gateae and Mycoplasma canadense with nucleotide similarities of 99 and 98 %, respectively. Nucleotide analysis of other genetic loci revealed 73-91 % nucleotide similarity to the corresponding genes of the above closely related species. All five strains clustered into a distinct group on the 16S rRNA and rpoB phylogenetic trees. Serological testing via growth inhibition and metabolic inhibition tests employing antiserum to type strains of M. phocicerebrale, M. arginini, M. gateae and M. canadense failed to recognize these novel strains. Our results suggest that the strains isolated from southern sea otters represent a novel species of the genus Mycoplasma, for which the name Mycoplasmaenhydrae sp. nov. is proposed; the type strain is 6243-11T (=DSM 106704T=ATCC TSD-140T).}, } @article {pmid30543508, year = {2018}, author = {Yang, RQ and Zhang, BL and Sun, HL and Zhang, GS and Li, SW and Liu, GX and Chen, T and Li, YS and Wu, YN and An, LZ and Zhang, W and Wu, XK}, title = {Nocardia mangyaensis sp. nov., a novel actinomycete isolated from crude-oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003159}, pmid = {30543508}, issn = {1466-5034}, abstract = {A Gram-stain-positive, aerobic, non-motile and mycolic-acid-containing strain, designated Y48T, was isolated from soil contaminated by crude oil located in the northern margin of the Qaidam Basin. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain Y48T belongs to the genus Nocardia and is closely related to N. cummidelens DSM 44490T (99.0 % similarity), N. soli DSM 44488T (99.0 %), N. lasii 3C-HV12T (98.9 %), N. salmonicida NBRC 13393T (98.6 %), N. ignorata NBRC 108230T (98.6 %) and N. coubleae NBRC 108252T (98.6 %). The average nucleotide identity and DNA-DNA hybridization values between strain Y48T and the reference strains were 75.9-84.5 and 27.5-29.0 %, respectively, values that were below the thresholds for species delineation. Chemotaxonomic analysis indicated that the major fatty acids of strain Y48T were C16 : 0, summed feature 3 (C16 : 1ω6c/C16 : 1ω7c), C18 : 1ω9c and C18 : 0 10-methyl (TBSA). The respiratory quinone was MK-8(H4, ω-cycl). The polar lipid profile was composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, two glycolipids and three unidentified lipids. The cell-wall hydrolysates contained meso-diaminopimelic acid, with ribose, arabinose, glucose and galactose as whole-cell sugars. A combination of 16S rRNA gene sequence analysis, and phenotypic and chemotaxonomic characterizations demonstrated that strain Y48T represents a novel species of the genus Nocardia, for which the name Nocardia mangyaensis sp. nov. is proposed. The type strain is Y48T (=JCM 32795T=CGMCC 4.7494T).}, } @article {pmid30543505, year = {2018}, author = {Liu, J and Ren, Q and Zhang, Y and Li, Y and Tian, X and Wu, Y and Tian, J and Zhang, XH}, title = {Alcanivorax profundi sp. nov., isolated from deep seawater of the Mariana Trench.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003145}, pmid = {30543505}, issn = {1466-5034}, abstract = {A Gram-stain-negative, rod-shaped, non-motile, strictly aerobic strain, designated as MTEO17T, was isolated from a 1000 m deep seawater sample of the Mariana Trench. Growth was observed at 10-45 °C (optimum, 37 °C), in the presence of 0.0-12.0 % NaCl (w/v; optimum, 3.0 %) and at pH 6.0-10.0 (optimum, pH 7.0-8.0). Phylogenetic analysis, based on the 16S rRNA gene sequence, revealed that strain MTEO17T belonged to the genus Alcanivorax and showed the highest sequence similarity of 97.9 % to Alcanivorax nanhaiticus MCCC 1A05629T. The estimated average nucleotide identity and DNA-DNA hybridization values between strain MTEO17T and A. nanhaiticus MCCC 1A05629T were 78.98 and 23.80 %, respectively. The significant dominant fatty acids were C16 : 0, summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c) and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The polar lipids comprised two phosphatidylethanolamines, one phosphatidylglycerol, one unidentified phospholipid and four unidentified polar lipids. The DNA G+C content of strain MTEO17T was 57.5 %. On the basis of the polyphasic evidence, strain MTEO17T is proposed to represent a novel species of the genus Alcanivorax, for which the name Alcanivoraxprofundi sp. nov. is proposed. The type strain is MTEO17T (=KCTC 52694T=MCCC 1K03252T).}, } @article {pmid30543504, year = {2018}, author = {Chai, C and Liu, W and Cheng, H and Hui, F}, title = {Mucor chuxiongensis sp. nov., a novel fungal species isolated from rotten wood.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003166}, pmid = {30543504}, issn = {1466-5034}, abstract = {Three strains of a novel mucoralean fungus were isolated from samples of decayed wood, which were collected from three locations near the city of Chuxiong, Yunnan province, China. These isolates were identified as a novel species through comparison of sequences in the ITS sequence, the D1/D2 domains of the LSU rRNA gene, and other taxonomic characteristics. The results demonstrated that these isolates represent a novel mucoralean fungus species belonging to the genus Mucor. The ITS sequence of Mucor chuxiongensissp. nov. differed from its closest relative, Mucor guilliermondii CBS 174.27T, by 13.1 % sequence divergence (39 substitutions and 38 gaps), and the D1/D2 sequences of the novel strains differed by 13 nt substitutions and one gap (1.9 %) from the ex-type strain. On potato dextrose agar, malt extract agar and synthetic mucor agar, the isolates grew slowly below 10 °C, rapidly at 25-30 °C, and could not grow well at 35 °C. The holotype strain of Mucor chuxiongensis sp. nov. is NYNU 174111 (CICC 41666T=CBS 143707T).}, } @article {pmid30543503, year = {2018}, author = {Liu, L and Hui, N and Liang, L and Zhang, X and Sun, Q and Li, L}, title = {Sphingomonas deserti sp. nov., isolated from Mu Us Sandy Land soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003168}, pmid = {30543503}, issn = {1466-5034}, abstract = {A Gram-stain-negative, rod-shaped bacterium, designated as strain GL-C-18T, was isolated from soil sample collected at Mu Us Sandy Land, China, and its taxonomic position was investigated using a polyphasic approach. Growth was observed in the presence of 0-1 % (w/v) NaCl (optimum, 0 %), pH 6.0-9.0 (optimum, pH 7.0-8.0) and 20-37 °C. On the basis of 16S rRNA gene sequence similarity, strain GL-C-18T belonged to the family Sphingomonadaceae and was most closely related to Sphingosinicella vermicomposti YC7378T (95.7 %), Sphingomonas oligophenolica S213T (95.0 %) and Sphingobium boeckii 301T (94.8 %). The draft genome of strain GL-C-18T was 6.09 Mb, and the G+C content was 66.0 %. The average nucleotide identity value to Sphingosinicella vermicomposti YC7378T was 83.7 %. The predominant respiratory quinone was Q-10. The major fatty acids were C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16:0 and C14 : 0 2OH. The main polar lipids were sphingoglycolipid, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. On the basis of chemotaxonomic, phylogenetic and phenotypic evidence, strain GL-C-18T represents a novel species of the genus Sphingomonas, for which the name Sphingomonasdeserti sp. nov. is proposed. The type strain is GL-C-18T (=ACCC 60076T=KCTC 62411T).}, } @article {pmid30543502, year = {2018}, author = {Ding, ZG and Ji, Y and Yin, M and Zhao, YR and Feng, YZ and Chunyu, WX and Tang, SK}, title = {Phytoactinopolyspora halophila sp. nov., a halophilic actinomycete isolated from a saline soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003153}, pmid = {30543502}, issn = {1466-5034}, abstract = {A novel halophilic actinobacterial strain, designated YIM 96934T, was isolated from a soil sample collected from the edge of a saline lake in Xinjiang, north-west China. The taxonomic position of the strain was investigated using a polyphasic approach. Cells of the strain were aerobic and Gram-stain-positive. On the basis of 16S rRNA gene sequence analysis, strain YIM 96934T was related most closely to type strains of the genus Phytoactinopolyspora, and shared highest sequence similarity with Phytoactinopolyspora endophytica EGI 60009T (94.7 %), Phytoactinopolyspora alkaliphila EGI 80629T (94.5 %) and Phytoactinopolyspora halotolerans YIM 96448T (94.1 %). Optimum growth of the strain was observed at 28-37 °C (range 15-45 °C), pH 7.0-8.0 (6.0-9.0) and 5-8 % (w/v) NaCl (2-24 %). The major isoprenoid quinone was MK-9(H4). The whole-cell sugars were glucose, galactose, mannose and rhamnose. The diagnostic diamino acid was ll-diaminopimelic acid. The polar lipid profile was found to consist of diphosphatidylglycerol, four unidentified phospholipids, three unidentified phosphoglycolipids, an unidentified aminophospholipid, two phosphatidylinositol mannosides and an unidentified polar lipid. The major fatty acids were anteiso-C15 : 0, iso-C16 : 0, iso-C17 : 0, anteiso-C17 : 0 and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B). The DNA G+C content was 66.6 mol%. On the basis of phenotypic, genotypic and phylogenetic data, a novel species, Phytoactinopolyspora halophila sp. nov., is proposed. The type strain is YIM 96934T (=KCTC 39926T=CCTCC AB 2017057T).}, } @article {pmid30543322, year = {2018}, author = {Li, L and Gui, YH and Xu, QH and Lin, HW and Lu, YH}, title = {Spongiactinospora rosea gen. nov., sp. nov., a new member of the family Streptosporangiaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003165}, pmid = {30543322}, issn = {1466-5034}, abstract = {A novel aerobic, spore-forming, marine actinomycete, designated strain LHW63015T, was isolated from a Craniella marine sponge collected in the South China Sea. The strain formed extensively branched substrate and aerial mycelia which carried long and crooked spore chains composed of ridged spores and spherical pseudosporangia. Strain LHW63015T contained meso-diaminopimelic acid as the diagnostic diamino acid. Glucose, ribose, mannose, galactose and madurose occured in whole-cell hydrolysates. The predominant polar lipids were hydroxyl-phosphatidylethanolamine, phosphoglycolipid and ninhydrin-positive phosphoglycolipid. MK-10(H4) and MK-10(H6) were the predominant menaquinones. The major fatty acids were 10-methyl C17 : 0 and C17 : 1ω8c. The G+C content of the genomic DNA was 70.8 mol%. In phylogenetic analysis based on 16S rRNA gene sequences, strain LHW63015T fell within the family Streptosporangiaceae and formed a distinct monophyletic lineage adjacent to the genus Sphaerisporangium, and shared the highest 16S rRNA gene sequence similarity of 96.2 % with Sphaerisporangium album YIM 48782T. On the basis of the polyphasic evidence, a novel genus and species of the family Streptosporangiaceae, for which the name Spongiactinospora rosea gen. nov., sp. nov., is proposed, with the type strain LHW63015T (=DSM 106635T=CCTCC AA 2018019T).}, } @article {pmid30543321, year = {2018}, author = {Tindall, BJ}, title = {Names above the rank of genus; the radical approach.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003169}, pmid = {30543321}, issn = {1466-5034}, abstract = {The International Code of Nomenclature of Prokaryotes currently caters for the names of ranks from class to subspecies. The form of names and their typification is dealt with under Rules 7-22. The nature of names at different ranks has a direct influence on the structure of the Code. However, with minor changes it is possible to simplify the structure and the links between names and their nomenclatural types, even if the proposed solution may cause some changes that create a degree of upheaval in the short term.}, } @article {pmid30543317, year = {2018}, author = {Xin, D and Bisgaard, M and Busse, HJ and Olsen, RH and Hess, C and Aalbæk, B and Olsen, JE and Christensen, H}, title = {Reclassification of Bisgaard taxon 37 and taxon 44 as Psittacicella melopsittaci gen. nov., sp. nov., Psittacicella hinzii sp. nov. and Psittacicella gerlachiana sp. nov. within Psittacicellaceae fam. nov. of the order Pasteurellales.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003133}, pmid = {30543317}, issn = {1466-5034}, abstract = {Bacteria isolated from lesions as well as apparently normal tissues of psittacine birds have previously been reported as taxon 37 and taxon 44 of Bisgaard. 16S rRNA gene sequence comparisons revealed a distant relationship to members of Pasteurellaceae at the species, genus and family levels. The polar lipid profile consisted of the major components phosphatidylethanolamine and phosphatidylglycerol. A new family Psittacicellaceae fam. nov. is proposed with the type genus Psittacicella gen. nov. The new genus Psittacicella includes the type species Psittacicella melopsittaci sp. nov. with type strain B96/4T (=CCUG 70858T=DSM 105476T), Psittacicella hinzii sp. nov. with type strain 111T (=CCUG 52861T=CCM 8842T) and Psittacicella gerlachiana sp. nov. with type strain EEAB3T1T (=CCUG 70857T=DSM 105477T). In addition to the major polar lipids, strain 111T possessed the non-identified aminophospholipids APL1 and APL2 and trace amounts of four lipids (L1-L4) whereas strain B94/4T showed the minor unidentified aminophospholipids APL3 and APL2 and trace amounts of unidentified lipid L3. These results demonstrate that strain B96/4T can be distinguished from 111T based on presence/absence of the unidentified lipids APL1 and APL3. The total polar lipid profile of strain EEAB3T1T differed from B96/4Tonly in one minor lipid. Strain B96/4T can further be distinguished from 111T by acid formation from trehalose and raffinose and the α-glucosidase test. Strains 111T and EEAB3T1T can be separated based on acid formation from trehalose and the α-glucosidase test. Strains B96/4T and EEAB3T1T can be separated by acid formation from raffinose and eight signature indels in the RpoB protein.}, } @article {pmid30542916, year = {2018}, author = {Guo, R and Liu, H and Li, X and Yang, Q and Jia, L and Zheng, Y and Li, W}, title = {Subgingival Microbial Changes During the First 3 Months of Fixed Appliance Treatment in Female Adult Patients.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1610-1}, pmid = {30542916}, issn = {1432-0991}, abstract = {Although periodontal diseases during fixed appliance treatment are a common issue, few studies have focused on the clinical and microbial factors associated with orthodontic appliances. Hence, we investigated changes in the subgingival microbial community and their association with periodontal changes at the early stage of fixed appliance treatment. Subgingival plaques from ten female patients with fixed appliances were obtained at three time points: before, 1 month and 3 months after the placement of the brackets (T0, T1 and T2). The 16S rRNA gene sequencing was used to analyze the microbial community of the subgingival plaque. The Plaque Index (PI) and Gingival Bleeding Index (GBI) were also recorded. The GBI significantly increased at T2, and the PI showed a temporary increase without a significant difference. The alpha diversity indices were stable. However, the beta diversity was significantly higher at T2 compared to T0 and T1. The relative abundance of core microbiomes at the genus level was relatively stable. Four periodontal pathogens at the species level, including Prevotella intermedia (Pi), Campylobacer rectus (Cr), Fusobacterium nucleatum (Fn), and Treponema denticola (Td), increased without significant differences. The subgingival microbial community affected by fixed appliance treatment might cause transient mild gingival inflammation.}, } @article {pmid30542915, year = {2018}, author = {Zhang, W and Gong, J and Wu, S and Yin, H and Jin, Y and Wu, H and Li, P and Wang, R}, title = {Draft genome Sequence of Phosphate-Accumulating Bacterium Acinetobacter tandoii SC36 from a Mangrove Wetland Ecosystem Provides Insights into Elements of Phosphorus Removal.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1611-0}, pmid = {30542915}, issn = {1432-0991}, support = {41366001//National Natural Science Foundation of China/ ; Hnky2017ZD-13//Education Bureau of Hainan Province/ ; }, abstract = {Acinetobacter tandoii SC36 was isolated from a mangrove wetland ecosystem in the Dongzhaigang Nature Reserve in Haikou, China. This bacterium was found to have a capacity for polyphosphate accumulation. To provide insight into its phosphorus metabolism and facilitate its application in phosphorus removal, we developed a draft genome of this strain. KEGG (Kyoto Encyclopedia of Genes and Genomes) annotation revealed three ppk genes and several phosphate metabolic related pathways in the genome of SC36. These genome data of Acinetobacter tandoii SC36 will facilitate elucidation of the mechanism of polyphosphate accumulation.}, } @article {pmid30542201, year = {2018}, author = {Röttjers, L and Faust, K}, title = {Can we predict keystones?.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0132-y}, pmid = {30542201}, issn = {1740-1534}, } @article {pmid30542200, year = {2018}, author = {}, title = {Imprisoned academics, China's Moon lander and AI moral code.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {166-167}, doi = {10.1038/d41586-018-07667-5}, pmid = {30542200}, issn = {1476-4687}, } @article {pmid30542199, year = {2018}, author = {Yang, C and Inoue, Y}, title = {An exciting tool for asymmetric synthesis.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {197-199}, doi = {10.1038/d41586-018-07625-1}, pmid = {30542199}, issn = {1476-4687}, } @article {pmid30542198, year = {2018}, author = {RIddell, SR}, title = {Adrenaline fuels a cytokine storm during immunotherapy.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {194-196}, doi = {10.1038/d41586-018-07581-w}, pmid = {30542198}, issn = {1476-4687}, } @article {pmid30542197, year = {2018}, author = {}, title = {A guide to the Nature Index.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S73}, doi = {10.1038/d41586-018-07696-0}, pmid = {30542197}, issn = {1476-4687}, } @article {pmid30542196, year = {2018}, author = {Keener, A}, title = {The genetic shortcut to antibody drugs.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S16-S17}, doi = {10.1038/d41586-018-07645-x}, pmid = {30542196}, issn = {1476-4687}, } @article {pmid30542195, year = {2018}, author = {Armitage, C}, title = {All eyes on the prize.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S57}, doi = {10.1038/d41586-018-07687-1}, pmid = {30542195}, issn = {1476-4687}, } @article {pmid30542194, year = {2018}, author = {Zastrow, M}, title = {China's place among the stars.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S64-S65}, doi = {10.1038/d41586-018-07690-6}, pmid = {30542194}, issn = {1476-4687}, } @article {pmid30542193, year = {2018}, author = {Jia, H}, title = {Yielding results to feed a people.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S62-S63}, doi = {10.1038/d41586-018-07689-z}, pmid = {30542193}, issn = {1476-4687}, } @article {pmid30542192, year = {2018}, author = {O'Meara, S}, title = {Small science grows large in new hands.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S65-S66}, doi = {10.1038/d41586-018-07691-5}, pmid = {30542192}, issn = {1476-4687}, } @article {pmid30542191, year = {2018}, author = {Brody, H}, title = {Gene therapy.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S5}, doi = {10.1038/d41586-018-07639-9}, pmid = {30542191}, issn = {1476-4687}, } @article {pmid30542190, year = {2018}, author = {Mallapaty, S}, title = {Engineering a biomedical revolution.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S66-S68}, doi = {10.1038/d41586-018-07692-4}, pmid = {30542190}, issn = {1476-4687}, } @article {pmid30542189, year = {2018}, author = {Arney, K}, title = {Change the genes to fix the skin.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S14-S15}, doi = {10.1038/d41586-018-07640-2}, pmid = {30542189}, issn = {1476-4687}, } @article {pmid30542188, year = {2018}, author = {Huang, F}, title = {Quality deficit belies the hype.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S70-S71}, doi = {10.1038/d41586-018-07694-2}, pmid = {30542188}, issn = {1476-4687}, } @article {pmid30542187, year = {2018}, author = {DeWeerdt, S}, title = {Prenatal gene therapy offers the earliest possible cure.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S6-S8}, doi = {10.1038/d41586-018-07643-z}, pmid = {30542187}, issn = {1476-4687}, } @article {pmid30542186, year = {2018}, author = {Jia, H}, title = {Strong spending compounds chemistry prowess.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S68-S69}, doi = {10.1038/d41586-018-07693-3}, pmid = {30542186}, issn = {1476-4687}, } @article {pmid30542185, year = {2018}, author = {Bender, E}, title = {Regulating the gene-therapy revolution.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S20-S22}, doi = {10.1038/d41586-018-07641-1}, pmid = {30542185}, issn = {1476-4687}, } @article {pmid30542184, year = {2018}, author = {Nogrady, B}, title = {How Indian biotech is driving innovation.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S53-S55}, doi = {10.1038/d41586-018-07671-9}, pmid = {30542184}, issn = {1476-4687}, } @article {pmid30542183, year = {2018}, author = {Nowogrodzki, A}, title = {Gene therapy targets sickle-cell disease.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S12-S13}, doi = {10.1038/d41586-018-07646-w}, pmid = {30542183}, issn = {1476-4687}, } @article {pmid30542182, year = {2018}, author = {Drew, L}, title = {Gene therapy targets epilepsy.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S10-S11}, doi = {10.1038/d41586-018-07644-y}, pmid = {30542182}, issn = {1476-4687}, } @article {pmid30542181, year = {2018}, author = {Savage, N}, title = {Designer viruses could be the secret to cheaper and better gene therapy.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S18-S19}, doi = {10.1038/d41586-018-07647-9}, pmid = {30542181}, issn = {1476-4687}, } @article {pmid30542180, year = {2018}, author = {Clayton, EW}, title = {A genetically augmented future.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S9}, doi = {10.1038/d41586-018-07642-0}, pmid = {30542180}, issn = {1476-4687}, } @article {pmid30542179, year = {2018}, author = {Sherman, M}, title = {Access and affordability for all.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S23}, doi = {10.1038/d41586-018-07648-8}, pmid = {30542179}, issn = {1476-4687}, } @article {pmid30542178, year = {2018}, author = {Larivière, V and Gong, K and Sugimoto, CR}, title = {Citations strength begins at home.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {S70-S71}, doi = {10.1038/d41586-018-07695-1}, pmid = {30542178}, issn = {1476-4687}, } @article {pmid30542177, year = {2018}, author = {Rivron, N and Pera, M and Rossant, J and Martinez Arias, A and Zernicka-Goetz, M and Fu, J and van den Brink, S and Bredenoord, A and Dondorp, W and de Wert, G and Hyun, I and Munsie, M and Isasi, R}, title = {Debate ethics of embryo models from stem cells.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {183-185}, doi = {10.1038/d41586-018-07663-9}, pmid = {30542177}, issn = {1476-4687}, } @article {pmid30542176, year = {2018}, author = {Fox, D}, title = {The hunt for life below Antarctic ice.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {180-182}, doi = {10.1038/d41586-018-07669-3}, pmid = {30542176}, issn = {1476-4687}, } @article {pmid30542175, year = {2018}, author = {Ham, YG}, title = {El Niño events will intensify under global warming.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {192-193}, doi = {10.1038/d41586-018-07638-w}, pmid = {30542175}, issn = {1476-4687}, } @article {pmid30542174, year = {2018}, author = {Wahls, WP}, title = {NIH dollars go to too few US states.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {190}, doi = {10.1038/d41586-018-07722-1}, pmid = {30542174}, issn = {1476-4687}, mesh = {*National Institutes of Health (U.S.) ; *Research Support as Topic ; United States ; }, } @article {pmid30542173, year = {2018}, author = {Collord, G and Nangalia, J and Moore, L}, title = {No place for 'trial by media' in bullying allegations.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {190}, doi = {10.1038/d41586-018-07723-0}, pmid = {30542173}, issn = {1476-4687}, } @article {pmid30542172, year = {2018}, author = {Akabayashi, A and Nakazawa, E and Caplan, AL}, title = {Gene editing: who should decide?.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {190}, doi = {10.1038/d41586-018-07720-3}, pmid = {30542172}, issn = {1476-4687}, } @article {pmid30542170, year = {2018}, author = {Ball, P}, title = {India: a turbulent tale of rivers, floods and monsoons.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {186-188}, doi = {10.1038/d41586-018-07678-2}, pmid = {30542170}, issn = {1476-4687}, } @article {pmid30542169, year = {2018}, author = {Searchinger, TD and Wirsenius, S and Beringer, T and Dumas, P}, title = {Assessing the efficiency of changes in land use for mitigating climate change.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {249-253}, doi = {10.1038/s41586-018-0757-z}, pmid = {30542169}, issn = {1476-4687}, abstract = {Land-use changes are critical for climate policy because native vegetation and soils store abundant carbon and their losses from agricultural expansion, together with emissions from agricultural production, contribute about 20 to 25 per cent of greenhouse gas emissions1,2. Most climate strategies require maintaining or increasing land-based carbon3 while meeting food demands, which are expected to grow by more than 50 per cent by 20501,2,4. A finite global land area implies that fulfilling these strategies requires increasing global land-use efficiency of both storing carbon and producing food. Yet measuring the efficiency of land-use changes from the perspective of greenhouse gas emissions is challenging, particularly when land outputs change, for example, from one food to another or from food to carbon storage in forests. Intuitively, if a hectare of land produces maize well and forest poorly, maize should be the more efficient use of land, and vice versa. However, quantifying this difference and the yields at which the balance changes requires a common metric that factors in different outputs, emissions from different agricultural inputs (such as fertilizer) and the different productive potentials of land due to physical factors such as rainfall or soils. Here we propose a carbon benefits index that measures how changes in the output types, output quantities and production processes of a hectare of land contribute to the global capacity to store carbon and to reduce total greenhouse gas emissions. This index does not evaluate biodiversity or other ecosystem values, which must be analysed separately. We apply the index to a range of land-use and consumption choices relevant to climate policy, such as reforesting pastures, biofuel production and diet changes. We find that these choices can have much greater implications for the climate than previously understood because standard methods for evaluating the effects of land use4-11 on greenhouse gas emissions systematically underestimate the opportunity of land to store carbon if it is not used for agriculture.}, } @article {pmid30542168, year = {2018}, author = {Dixon, V}, title = {Cold heart.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {296}, doi = {10.1038/d41586-018-07680-8}, pmid = {30542168}, issn = {1476-4687}, } @article {pmid30542167, year = {2018}, author = {Cha, J and Kim, KW and Daraio, C}, title = {Experimental realization of on-chip topological nanoelectromechanical metamaterials.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {229-233}, doi = {10.1038/s41586-018-0764-0}, pmid = {30542167}, issn = {1476-4687}, abstract = {Guiding waves through a stable physical channel is essential for reliable information transport. However, energy transport in high-frequency mechanical systems, such as in signal-processing applications1, is particularly sensitive to defects and sharp turns because of back-scattering and losses2. Topological phenomena in condensed matter systems have shown immunity to defects and unidirectional energy propagation3. Topological mechanical metamaterials translate these properties into classical systems for efficient phononic energy transport. Acoustic and mechanical topological metamaterials have so far been realized only in large-scale systems, such as arrays of pendulums4, gyroscopic lattices5,6, structured plates7,8 and arrays of rods, cans and other structures acting as acoustic scatterers9-12. To fulfil their potential in device applications, mechanical topological systems need to be scaled to the on-chip level for high-frequency transport13-15. Here we report the experimental realization of topological nanoelectromechanical metamaterials, consisting of two-dimensional arrays of free-standing silicon nitride nanomembranes that operate at high frequencies (10-20 megahertz). We experimentally demonstrate the presence of edge states, and characterize their localization and Dirac-cone-like frequency dispersion. Our topological waveguides are also robust to waveguide distortions and pseudospin-dependent transport. The on-chip integrated acoustic components realized here could be used in unidirectional waveguides and compact delay lines for high-frequency signal-processing applications.}, } @article {pmid30542166, year = {2018}, author = {Cai, W and Wang, G and Dewitte, B and Wu, L and Santoso, A and Takahashi, K and Yang, Y and Carréric, A and McPhaden, MJ}, title = {Increased variability of eastern Pacific El Niño under greenhouse warming.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {201-206}, doi = {10.1038/s41586-018-0776-9}, pmid = {30542166}, issn = {1476-4687}, abstract = {The El Niño-Southern Oscillation (ENSO) is the dominant and most consequential climate variation on Earth, and is characterized by warming of equatorial Pacific sea surface temperatures (SSTs) during the El Niño phase and cooling during the La Niña phase. ENSO events tend to have a centre-corresponding to the location of the maximum SST anomaly-in either the central equatorial Pacific (5° S-5° N, 160° E-150° W) or the eastern equatorial Pacific (5° S-5° N, 150°-90° W); these two distinct types of ENSO event are referred to as the CP-ENSO and EP-ENSO regimes, respectively. How the ENSO may change under future greenhouse warming is unknown, owing to a lack of inter-model agreement over the response of SSTs in the eastern equatorial Pacific to such warming. Here we find a robust increase in future EP-ENSO SST variability among CMIP5 climate models that simulate the two distinct ENSO regimes. We show that the EP-ENSO SST anomaly pattern and its centre differ greatly from one model to another, and therefore cannot be well represented by a single SST 'index' at the observed centre. However, although the locations of the anomaly centres differ in each model, we find a robust increase in SST variability at each anomaly centre across the majority of models considered. This increase in variability is largely due to greenhouse-warming-induced intensification of upper-ocean stratification in the equatorial Pacific, which enhances ocean-atmosphere coupling. An increase in SST variance implies an increase in the number of 'strong' EP-El Niño events (corresponding to large SST anomalies) and associated extreme weather events.}, } @article {pmid30542165, year = {2018}, author = {Wengerowsky, S and Joshi, SK and Steinlechner, F and Hübel, H and Ursin, R}, title = {An entanglement-based wavelength-multiplexed quantum communication network.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {225-228}, doi = {10.1038/s41586-018-0766-y}, pmid = {30542165}, issn = {1476-4687}, abstract = {Quantum key distribution1 has reached the level of maturity required for deployment in real-world scenarios2-6. It has previously been shown to operate alongside classical communication in the same telecommunication fibre7-9 and over long distances in fibre10,11 and in free-space links12-15. Despite these advances, the practical applicability of quantum key distribution is curtailed by the fact that most implementations and protocols are limited to two communicating parties. Quantum networks scale the advantages of quantum key distribution protocols to more than two distant users. Here we present a fully connected quantum network architecture in which a single entangled photon source distributes quantum states to many users while minimizing the resources required for each. Further, it does so without sacrificing security or functionality relative to two-party communication schemes. We demonstrate the feasibility of our approach using a single source of bipartite polarization entanglement, which is multiplexed into 12 wavelength channels. Six states are then distributed between four users in a fully connected graph using only one fibre and one polarization analysis module per user. Because no adaptations of the entanglement source are required to add users, the network can readily be scaled to a large number of users, without requiring trust in the provider of the source. Unlike previous attempts at multi-user networks, which have been based on active optical switches and therefore limited to some duty cycle, our implementation is fully passive and thus has the potential for unprecedented quantum communication speeds.}, } @article {pmid30542164, year = {2018}, author = {Staedtke, V and Bai, RY and Kim, K and Darvas, M and Davila, ML and Riggins, GJ and Rothman, PB and Papadopoulos, N and Kinzler, KW and Vogelstein, B and Zhou, S}, title = {Disruption of a self-amplifying catecholamine loop reduces cytokine release syndrome.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {273-277}, doi = {10.1038/s41586-018-0774-y}, pmid = {30542164}, issn = {1476-4687}, support = {U54 CA196519/CA/NCI NIH HHS/United States ; P50 CA062924/CA/NCI NIH HHS/United States ; K08 CA230179/CA/NCI NIH HHS/United States ; R25 NS065729/NS/NINDS NIH HHS/United States ; R03 CA178118/CA/NCI NIH HHS/United States ; }, abstract = {Cytokine release syndrome (CRS) is a life-threatening complication of several new immunotherapies used to treat cancers and autoimmune diseases1-5. Here we report that atrial natriuretic peptide can protect mice from CRS induced by such agents by reducing the levels of circulating catecholamines. Catecholamines were found to orchestrate an immunodysregulation resulting from oncolytic bacteria and lipopolysaccharide through a self-amplifying loop in macrophages. Myeloid-specific deletion of tyrosine hydroxylase inhibited this circuit. Cytokine release induced by T-cell-activating therapeutic agents was also accompanied by a catecholamine surge and inhibition of catecholamine synthesis reduced cytokine release in vitro and in mice. Pharmacologic catecholamine blockade with metyrosine protected mice from lethal complications of CRS resulting from infections and various biotherapeutic agents including oncolytic bacteria, T-cell-targeting antibodies and CAR-T cells. Our study identifies catecholamines as an essential component of the cytokine release that can be modulated by specific blockers without impairing the therapeutic response.}, } @article {pmid30542163, year = {2018}, author = {Hölzl-Hobmeier, A and Bauer, A and Silva, AV and Huber, SM and Bannwarth, C and Bach, T}, title = {Catalytic deracemization of chiral allenes by sensitized excitation with visible light.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {240-243}, doi = {10.1038/s41586-018-0755-1}, pmid = {30542163}, issn = {1476-4687}, abstract = {Chiral compounds exist as enantiomers that are non-superimposable mirror images of each other. Owing to the importance of enantiomerically pure chiral compounds1-for example, as active pharmaceutical ingredients-separation of racemates (1:1 mixtures of enantiomers) is extensively performed2. Frequently, however, only a single enantiomeric form of a chiral compound is required, which raises the question of how a racemate can be selectively converted into a single enantiomer. Such a deracemization3 process is entropically disfavoured and cannot be performed by a conventional catalyst in solution. Here we show that it is possible to photochemically deracemize chiral compounds with high enantioselectivity using irradiation with visible light (wavelength of 420 nanometres) in the presence of catalytic quantities (2.5 mole per cent) of a chiral sensitizer. We converted an array of 17 chiral racemic allenes into the respective single enantiomers with 89 to 97 per cent enantiomeric excess. The sensitizer is postulated to operate by triplet energy transfer to the allene, with different energy-transfer efficiencies for the two enantiomers. It thus serves as a unidirectional catalyst that converts one enantiomer but not the other, and the decrease in entropy is compensated by light energy. Photochemical deracemization enables the direct formation of enantiopure materials from a racemic mixture of the same compound, providing a novel approach to the challenge of creating asymmetry.}, } @article {pmid30542162, year = {2018}, author = {Schiermeier, Q}, title = {China backs bold plan to tear down journal paywalls.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {171-172}, doi = {10.1038/d41586-018-07659-5}, pmid = {30542162}, issn = {1476-4687}, } @article {pmid30542158, year = {2019}, author = {Shaik, MM and Peng, H and Lu, J and Rits-Volloch, S and Xu, C and Liao, M and Chen, B}, title = {Structural basis of coreceptor recognition by HIV-1 envelope spike.}, journal = {Nature}, volume = {565}, number = {7739}, pages = {318-323}, doi = {10.1038/s41586-018-0804-9}, pmid = {30542158}, issn = {1476-4687}, support = {R01 AI106488/AI/NIAID NIH HHS/United States ; R01 AI127193/AI/NIAID NIH HHS/United States ; R01 AI141002/AI/NIAID NIH HHS/United States ; R56 AI129721/AI/NIAID NIH HHS/United States ; }, abstract = {HIV-1 envelope glycoprotein (Env), which consists of trimeric (gp160)3 cleaved to (gp120 and gp41)3, interacts with the primary receptor CD4 and a coreceptor (such as chemokine receptor CCR5) to fuse viral and target-cell membranes. The gp120-coreceptor interaction has previously been proposed as the most crucial trigger for unleashing the fusogenic potential of gp41. Here we report a cryo-electron microscopy structure of a full-length gp120 in complex with soluble CD4 and unmodified human CCR5, at 3.9 Å resolution. The V3 loop of gp120 inserts into the chemokine-binding pocket formed by seven transmembrane helices of CCR5, and the N terminus of CCR5 contacts the CD4-induced bridging sheet of gp120. CCR5 induces no obvious allosteric changes in gp120 that can propagate to gp41; it does bring the Env trimer close to the target membrane. The N terminus of gp120, which is gripped by gp41 in the pre-fusion or CD4-bound Env, flips back in the CCR5-bound conformation and may irreversibly destabilize gp41 to initiate fusion. The coreceptor probably functions by stabilizing and anchoring the CD4-induced conformation of Env near the cell membrane. These results advance our understanding of HIV-1 entry into host cells and may guide the development of vaccines and therapeutic agents.}, } @article {pmid30542157, year = {2019}, author = {Khanday, I and Skinner, D and Yang, B and Mercier, R and Sundaresan, V}, title = {A male-expressed rice embryogenic trigger redirected for asexual propagation through seeds.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {91-95}, doi = {10.1038/s41586-018-0785-8}, pmid = {30542157}, issn = {1476-4687}, support = {IOS-1547760//National Science Foundation/International ; IOS-1810468//National Science Foundation/International ; IS10OD010786-01/OD/NIH HHS/United States ; CA-D-XXX-6973-H//US Department of Agriculture/International ; }, abstract = {The molecular pathways that trigger the initiation of embryogenesis after fertilization in flowering plants, and prevent its occurrence without fertilization, are not well understood1. Here we show in rice (Oryza sativa) that BABY BOOM1 (BBM1), a member of the AP2 family2 of transcription factors that is expressed in sperm cells, has a key role in this process. Ectopic expression of BBM1 in the egg cell is sufficient for parthenogenesis, which indicates that a single wild-type gene can bypass the fertilization checkpoint in the female gamete. Zygotic expression of BBM1 is initially specific to the male allele but is subsequently biparental, and this is consistent with its observed auto-activation. Triple knockout of the genes BBM1, BBM2 and BBM3 causes embryo arrest and abortion, which are fully rescued by male-transmitted BBM1. These findings suggest that the requirement for fertilization in embryogenesis is mediated by male-genome transmission of pluripotency factors. When genome editing to substitute mitosis for meiosis (MiMe)3,4 is combined with the expression of BBM1 in the egg cell, clonal progeny can be obtained that retain genome-wide parental heterozygosity. The synthetic asexual-propagation trait is heritable through multiple generations of clones. Hybrid crops provide increased yields that cannot be maintained by their progeny owing to genetic segregation. This work establishes the feasibility of asexual reproduction in crops, and could enable the maintenance of hybrids clonally through seed propagation5,6.}, } @article {pmid30542156, year = {2019}, author = {Wong, W and Huang, R and Menant, S and Hong, C and Sandow, JJ and Birkinshaw, RW and Healer, J and Hodder, AN and Kanjee, U and Tonkin, CJ and Heckmann, D and Soroka, V and Søgaard, TMM and Jørgensen, T and Duraisingh, MT and Czabotar, PE and de Jongh, WA and Tham, WH and Webb, AI and Yu, Z and Cowman, AF}, title = {Structure of Plasmodium falciparum Rh5-CyRPA-Ripr invasion complex.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {118-121}, doi = {10.1038/s41586-018-0779-6}, pmid = {30542156}, issn = {1476-4687}, abstract = {Plasmodium falciparum causes the severe form of malaria that has high levels of mortality in humans. Blood-stage merozoites of P. falciparum invade erythrocytes, and this requires interactions between multiple ligands from the parasite and receptors in hosts. These interactions include the binding of the Rh5-CyRPA-Ripr complex with the erythrocyte receptor basigin1,2, which is an essential step for entry into human erythrocytes. Here we show that the Rh5-CyRPA-Ripr complex binds the erythrocyte cell line JK-1 significantly better than does Rh5 alone, and that this binding occurs through the insertion of Rh5 and Ripr into host membranes as a complex with high molecular weight. We report a cryo-electron microscopy structure of the Rh5-CyRPA-Ripr complex at subnanometre resolution, which reveals the organization of this essential invasion complex and the mode of interactions between members of the complex, and shows that CyRPA is a critical mediator of complex assembly. Our structure identifies blades 4-6 of the β-propeller of CyRPA as contact sites for Rh5 and Ripr. The limited contacts between Rh5-CyRPA and CyRPA-Ripr are consistent with the dissociation of Rh5 and Ripr from CyRPA for membrane insertion. A comparision of the crystal structure of Rh5-basigin with the cryo-electron microscopy structure of Rh5-CyRPA-Ripr suggests that Rh5 and Ripr are positioned parallel to the erythrocyte membrane before membrane insertion. This provides information on the function of this complex, and thereby provides insights into invasion by P. falciparum.}, } @article {pmid30542155, year = {2019}, author = {Salomon, G and Koepsell, J and Vijayan, J and Hilker, TA and Nespolo, J and Pollet, L and Bloch, I and Gross, C}, title = {Direct observation of incommensurate magnetism in Hubbard chains.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {56-60}, doi = {10.1038/s41586-018-0778-7}, pmid = {30542155}, issn = {1476-4687}, abstract = {The interplay between magnetism and doping is at the origin of exotic strongly correlated electronic phases and can lead to novel forms of magnetic ordering. One example is the emergence of incommensurate spin-density waves, which have wavevectors that do not belong to the reciprocal lattice. In one dimension this effect is a hallmark of Luttinger liquid theory, which also describes the low-energy physics of the Hubbard model1. Here we use a quantum simulator that uses ultracold fermions in an optical lattice2-8 to directly observe such incommensurate spin correlations in doped and spin-imbalanced Hubbard chains using fully spin- and density-resolved quantum gas microscopy. Doping is found to induce a linear change in the spin-density wavevector, in excellent agreement with predictions from Luttinger theory. For non-zero polarization we observe a reduction in the wavevector with magnetization, as expected from the antiferromagnetic Heisenberg model in a magnetic field. We trace the microscopic-scale origin of these incommensurate correlations to holes, doublons (double occupancies) and excess spins, which act as delocalized domain walls for the antiferromagnetic order. In addition, by inducing interchain coupling we observe fundamentally different spin correlations around doublons and suppression of incommensurate magnetism at finite (low) temperature in the two-dimensional regime9. Our results demonstrate how access to the full counting statistics of all local degrees of freedom can be used to study fundamental phenomena in strongly correlated many-body physics.}, } @article {pmid30542154, year = {2018}, author = {Myers, JB and Haddad, BG and O'Neill, SE and Chorev, DS and Yoshioka, CC and Robinson, CV and Zuckerman, DM and Reichow, SL}, title = {Structure of native lens connexin 46/50 intercellular channels by cryo-EM.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {372-377}, doi = {10.1038/s41586-018-0786-7}, pmid = {30542154}, issn = {1476-4687}, support = {R35 GM124779/GM/NIGMS NIH HHS/United States ; }, abstract = {Gap junctions establish direct pathways for cell-to-cell communication through the assembly of twelve connexin subunits that form intercellular channels connecting neighbouring cells. Co-assembly of different connexin isoforms produces channels with unique properties and enables communication across cell types. Here we used single-particle cryo-electron microscopy to investigate the structural basis of connexin co-assembly in native lens gap junction channels composed of connexin 46 and connexin 50 (Cx46/50). We provide the first comparative analysis to connexin 26 (Cx26), which-together with computational studies-elucidates key energetic features governing gap junction permselectivity. Cx46/50 adopts an open-state conformation that is distinct from the Cx26 crystal structure, yet it appears to be stabilized by a conserved set of hydrophobic anchoring residues. 'Hot spots' of genetic mutations linked to hereditary cataract formation map to the core structural-functional elements identified in Cx46/50, suggesting explanations for many of the disease-causing effects.}, } @article {pmid30542153, year = {2019}, author = {Huguenin-Dezot, N and Alonzo, DA and Heberlig, GW and Mahesh, M and Nguyen, DP and Dornan, MH and Boddy, CN and Schmeing, TM and Chin, JW}, title = {Trapping biosynthetic acyl-enzyme intermediates with encoded 2,3-diaminopropionic acid.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {112-117}, doi = {10.1038/s41586-018-0781-z}, pmid = {30542153}, issn = {1476-4687}, support = {P30 GM124165/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; }, abstract = {Many enzymes catalyse reactions that proceed through covalent acyl-enzyme (ester or thioester) intermediates1. These enzymes include serine hydrolases2,3 (encoded by one per cent of human genes, and including serine proteases and thioesterases), cysteine proteases (including caspases), and many components of the ubiquitination machinery4,5. Their important acyl-enzyme intermediates are unstable, commonly having half-lives of minutes to hours6. In some cases, acyl-enzyme complexes can be stabilized using substrate analogues or active-site mutations but, although these approaches can provide valuable insight7-10, they often result in complexes that are substantially non-native. Here we develop a strategy for incorporating 2,3-diaminopropionic acid (DAP) into recombinant proteins, via expansion of the genetic code11. We show that replacing catalytic cysteine or serine residues of enzymes with DAP permits their first-step reaction with native substrates, allowing the efficient capture of acyl-enzyme complexes that are linked through a stable amide bond. For one of these enzymes, the thioesterase domain of valinomycin synthetase12, we elucidate the biosynthetic pathway by which it progressively oligomerizes tetradepsipeptidyl substrates to a dodecadepsipeptidyl intermediate, which it then cyclizes to produce valinomycin. By trapping the first and last acyl-thioesterase intermediates in the catalytic cycle as DAP conjugates, we provide structural insight into how conformational changes in thioesterase domains of such nonribosomal peptide synthetases control the oligomerization and cyclization of linear substrates. The encoding of DAP will facilitate the characterization of diverse acyl-enzyme complexes, and may be extended to capturing the native substrates of transiently acylated proteins of unknown function.}, } @article {pmid30542152, year = {2018}, author = {Jackson, R and Kroehling, L and Khitun, A and Bailis, W and Jarret, A and York, AG and Khan, OM and Brewer, JR and Skadow, MH and Duizer, C and Harman, CCD and Chang, L and Bielecki, P and Solis, AG and Steach, HR and Slavoff, S and Flavell, RA}, title = {The translation of non-canonical open reading frames controls mucosal immunity.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {434-438}, doi = {10.1038/s41586-018-0794-7}, pmid = {30542152}, issn = {1476-4687}, support = {R01 GM122984/GM/NIGMS NIH HHS/United States ; T32 GM067543/GM/NIGMS NIH HHS/United States ; }, abstract = {The annotation of the mammalian protein-coding genome is incomplete. Arbitrary size restriction of open reading frames (ORFs) and the absolute requirement for a methionine codon as the sole initiator of translation have constrained the identification of potentially important transcripts with non-canonical protein-coding potential1,2. Here, using unbiased transcriptomic approaches in macrophages that respond to bacterial infection, we show that ribosomes associate with a large number of RNAs that were previously annotated as 'non-protein coding'. Although the idea that such non-canonical ORFs can encode functional proteins is controversial3,4, we identify a range of short and non-ATG-initiated ORFs that can generate stable and spatially distinct proteins. Notably, we show that the translation of a new ORF 'hidden' within the long non-coding RNA Aw112010 is essential for the orchestration of mucosal immunity during both bacterial infection and colitis. This work expands our interpretation of the protein-coding genome and demonstrates that proteinaceous products generated from non-canonical ORFs are crucial for the immune response in vivo. We therefore propose that the misannotation of non-canonical ORF-containing genes as non-coding RNAs may obscure the essential role of a multitude of previously undiscovered protein-coding genes in immunity and disease.}, } @article {pmid30542088, year = {2018}, author = {Holmes, K}, title = {Aaron Klug (1926-2018).}, journal = {Nature}, volume = {564}, number = {7736}, pages = {346}, doi = {10.1038/d41586-018-07702-5}, pmid = {30542088}, issn = {1476-4687}, } @article {pmid30541895, year = {2018}, author = {Luo, G and Ambati, A and Lin, L and Bonvalet, M and Partinen, M and Ji, X and Maecker, HT and Mignot, EJ}, title = {Autoimmunity to hypocretin and molecular mimicry to flu in type 1 narcolepsy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12323-E12332}, doi = {10.1073/pnas.1818150116}, pmid = {30541895}, issn = {1091-6490}, abstract = {Type 1 narcolepsy (T1N) is caused by hypocretin/orexin (HCRT) neuronal loss. Association with the HLA DQB1*06:02/DQA1*01:02 (98% vs. 25%) heterodimer (DQ0602), T cell receptors (TCR) and other immune loci suggest autoimmunity but autoantigens are unknown. Onset is seasonal and associated with influenza A, notably pandemic 2009 H1N1 (pH1N1) infection and vaccination (Pandemrix). Peptides derived from HCRT and influenza A, including pH1N1, were screened for DQ0602 binding and presence of cognate DQ0602 tetramer-peptide-specific CD4+ T cells tested in 35 T1N cases and 22 DQ0602 controls. Higher reactivity to influenza pHA273-287 (pH1N1 specific), PR8 (H1N1 pre-2009 and H2N2)-specific NP17-31 and C-amidated but not native version of HCRT54-66 and HCRT86-97 (HCRTNH2) were observed in T1N. Single-cell TCR sequencing revealed sharing of CDR3β TRBV4-2-CASSQETQGRNYGYTF in HCRTNH2 and pHA273-287-tetramers, suggesting molecular mimicry. This public CDR3β uses TRBV4-2, a segment modulated by T1N-associated SNP rs1008599, suggesting causality. TCR-α/β CDR3 motifs of HCRT54-66-NH2 and HCRT86-97-NH2 tetramers were extensively shared: notably public CDR3α, TRAV2-CAVETDSWGKLQF-TRAJ24, that uses TRAJ24, a chain modulated by T1N-associated SNPs rs1154155 and rs1483979. TCR-α/β CDR3 sequences found in pHA273-287, NP17-31, and HCRTNH2 tetramer-positive CD4+ cells were also retrieved in single INF-γ-secreting CD4+ sorted cells stimulated with Pandemrix, independently confirming these results. Our results provide evidence for autoimmunity and molecular mimicry with flu antigens modulated by genetic components in the pathophysiology of T1N.}, } @article {pmid30541894, year = {2019}, author = {Bayraktar, EC and Baudrier, L and Özerdem, C and Lewis, CA and Chan, SH and Kunchok, T and Abu-Remaileh, M and Cangelosi, AL and Sabatini, DM and Birsoy, K and Chen, WW}, title = {MITO-Tag Mice enable rapid isolation and multimodal profiling of mitochondria from specific cell types in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {303-312}, doi = {10.1073/pnas.1816656115}, pmid = {30541894}, issn = {1091-6490}, support = {F31 DK113665/DK/NIDDK NIH HHS/United States ; R01 CA103866/CA/NCI NIH HHS/United States ; R01 CA129105/CA/NCI NIH HHS/United States ; R37 AI047389/AI/NIAID NIH HHS/United States ; }, abstract = {Mitochondria are metabolic organelles that are essential for mammalian life, but the dynamics of mitochondrial metabolism within mammalian tissues in vivo remains incompletely understood. While whole-tissue metabolite profiling has been useful for studying metabolism in vivo, such an approach lacks resolution at the cellular and subcellular level. In vivo methods for interrogating organellar metabolites in specific cell types within mammalian tissues have been limited. To address this, we built on prior work in which we exploited a mitochondrially localized 3XHA epitope tag (MITO-Tag) for the fast isolation of mitochondria from cultured cells to generate MITO-Tag Mice. Affording spatiotemporal control over MITO-Tag expression, these transgenic animals enable the rapid, cell-type-specific immunoisolation of mitochondria from tissues, which we verified using a combination of proteomic and metabolomic approaches. Using MITO-Tag Mice and targeted and untargeted metabolite profiling, we identified changes during fasted and refed conditions in a diverse array of mitochondrial metabolites in hepatocytes and found metabolites that behaved differently at the mitochondrial versus whole-tissue level. MITO-Tag Mice should have utility for studying mitochondrial physiology, and our strategy should be generally applicable for studying other mammalian organelles in specific cell types in vivo.}, } @article {pmid30541893, year = {2019}, author = {Lacasa, L}, title = {Newcomb-Benford law helps customs officers to detect fraud in international trade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {11-13}, doi = {10.1073/pnas.1819470116}, pmid = {30541893}, issn = {1091-6490}, } @article {pmid30541892, year = {2018}, author = {Hu, H and Ataka, K and Menny, A and Fourati, Z and Sauguet, L and Corringer, PJ and Koehl, P and Heberle, J and Delarue, M}, title = {Electrostatics, proton sensor, and networks governing the gating transition in GLIC, a proton-gated pentameric ion channel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12172-E12181}, doi = {10.1073/pnas.1813378116}, pmid = {30541892}, issn = {1091-6490}, abstract = {The pentameric ligand-gated ion channel (pLGIC) from Gloeobacter violaceus (GLIC) has provided insightful structure-function views on the permeation process and the allosteric regulation of the pLGICs family. However, GLIC is activated by pH instead of a neurotransmitter and a clear picture for the gating transition driven by protons is still lacking. We used an electrostatics-based (finite difference Poisson-Boltzmann/Debye-Hückel) method to predict the acidities of all aspartic and glutamic residues in GLIC, both in its active and closed-channel states. Those residues with a predicted pKa close to the experimental pH50 were individually replaced by alanine and the resulting variant receptors were titrated by ATR/FTIR spectroscopy. E35, located in front of loop F far away from the orthosteric site, appears as the key proton sensor with a measured individual pKa at 5.8. In the GLIC open conformation, E35 is connected through a water-mediated hydrogen-bond network first to the highly conserved electrostatic triad R192-D122-D32 and then to Y197-Y119-K248, both located at the extracellular domain-transmembrane domain interface. The second triad controls a cluster of hydrophobic side chains from the M2-M3 loop that is remodeled during the gating transition. We solved 12 crystal structures of GLIC mutants, 6 of them being trapped in an agonist-bound but nonconductive conformation. Combined with previous data, this reveals two branches of a continuous network originating from E35 that reach, independently, the middle transmembrane region of two adjacent subunits. We conclude that GLIC's gating proceeds by making use of loop F, already known as an allosteric site in other pLGICs, instead of the classic orthosteric site.}, } @article {pmid30541891, year = {2018}, author = {Hamdan, FH and Johnsen, SA}, title = {DeltaNp63-dependent super enhancers define molecular identity in pancreatic cancer by an interconnected transcription factor network.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12343-E12352}, doi = {10.1073/pnas.1812915116}, pmid = {30541891}, issn = {1091-6490}, abstract = {Molecular subtyping of cancer offers tremendous promise for the optimization of a precision oncology approach to anticancer therapy. Recent advances in pancreatic cancer research uncovered various molecular subtypes with tumors expressing a squamous/basal-like gene expression signature displaying a worse prognosis. Through unbiased epigenome mapping, we identified deltaNp63 as a major driver of a gene signature in pancreatic cancer cell lines, which we report to faithfully represent the highly aggressive pancreatic squamous subtype observed in vivo, and display the specific epigenetic marking of genes associated with decreased survival. Importantly, depletion of deltaNp63 in these systems significantly decreased cell proliferation and gene expression patterns associated with a squamous subtype and transcriptionally mimicked a subtype switch. Using genomic localization data of deltaNp63 in pancreatic cancer cell lines coupled with epigenome mapping data from patient-derived xenografts, we uncovered that deltaNp63 mainly exerts its effects by activating subtype-specific super enhancers. Furthermore, we identified a group of 45 subtype-specific super enhancers that are associated with poorer prognosis and are highly dependent on deltaNp63. Genes associated with these enhancers included a network of transcription factors, including HIF1A, BHLHE40, and RXRA, which form a highly intertwined transcriptional regulatory network with deltaNp63 to further activate downstream genes associated with poor survival.}, } @article {pmid30541890, year = {2018}, author = {Luft, CDB and Zioga, I and Thompson, NM and Banissy, MJ and Bhattacharya, J}, title = {Right temporal alpha oscillations as a neural mechanism for inhibiting obvious associations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12144-E12152}, doi = {10.1073/pnas.1811465115}, pmid = {30541890}, issn = {1091-6490}, abstract = {Creative cognition requires mental exploration of remotely connected concepts while suppressing dominant ones. Across four experiments using different samples of participants, we provide evidence that right temporal alpha oscillations play a crucial role in inhibiting habitual thinking modes, thereby paving the way for accessing more remote ideas. In the first experiment, participants completed the compound remote associate task (RAT) in three separate sessions: during right temporal alpha (10 Hz) transcranial alternating current brain stimulation (tACS), left temporal alpha tACS, and sham tACS. Participants performed better under right tACS only on RAT items in which two of the three words shared misleading semantic associations. In the second experiment, we measured EEG while the participants solved RAT items with or without shared misleading associations. We observed an increase in right temporal alpha power when participants correctly solved RAT items with misleading semantic associations. The third experiment demonstrated that while solving divergent thinking tasks participants came up with more remote ideas when stimulated by right temporal alpha tACS. In the fourth experiment, we found that participants showed higher right temporal alpha power when generating more remote uses for common objects. These studies altogether indicate that right temporal alpha oscillations may support creativity by acting as a neural mechanism for an active inhibition of obvious semantic associations.}, } @article {pmid30541889, year = {2018}, author = {Bourbousse, C and Vegesna, N and Law, JA}, title = {SOG1 activator and MYB3R repressors regulate a complex DNA damage network in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12453-E12462}, doi = {10.1073/pnas.1810582115}, pmid = {30541889}, issn = {1091-6490}, abstract = {To combat DNA damage, organisms mount a DNA damage response (DDR) that results in cell cycle regulation, DNA repair and, in severe cases, cell death. Underscoring the importance of gene regulation in this response, studies in Arabidopsis have demonstrated that all of the aforementioned processes rely on SUPPRESSOR OF GAMMA RESPONSE 1 (SOG1), a NAC family transcription factor (TF) that has been functionally equated to the mammalian tumor suppressor, p53. However, the expression networks connecting SOG1 to these processes remain largely unknown and, although the DDR spans from minutes to hours, most transcriptomic data correspond to single time-point snapshots. Here, we generated transcriptional models of the DDR from GAMMA (γ)-irradiated wild-type and sog1 seedlings during a 24-hour time course using DREM, the Dynamic Regulatory Events Miner, revealing 11 coexpressed gene groups with distinct biological functions and cis-regulatory features. Within these networks, additional chromatin immunoprecipitation and transcriptomic experiments revealed that SOG1 is the major activator, directly targeting the most strongly up-regulated genes, including TFs, repair factors, and early cell cycle regulators, while three MYB3R TFs are the major repressors, specifically targeting the most strongly down-regulated genes, which mainly correspond to G2/M cell cycle-regulated genes. Together these models reveal the temporal dynamics of the transcriptional events triggered by γ-irradiation and connects these events to TFs and biological processes over a time scale commensurate with key processes coordinated in response to DNA damage, greatly expanding our understanding of the DDR.}, } @article {pmid30541888, year = {2018}, author = {Mathieu, M and Drelon, C and Rodriguez, S and Tabbal, H and Septier, A and Damon-Soubeyrand, C and Dumontet, T and Berthon, A and Sahut-Barnola, I and Djari, C and Batisse-Lignier, M and Pointud, JC and Richard, D and Kerdivel, G and Calméjane, MA and Boeva, V and Tauveron, I and Lefrançois-Martinez, AM and Martinez, A and Val, P}, title = {Steroidogenic differentiation and PKA signaling are programmed by histone methyltransferase EZH2 in the adrenal cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12265-E12274}, doi = {10.1073/pnas.1809185115}, pmid = {30541888}, issn = {1091-6490}, abstract = {Adrenal cortex steroids are essential for body homeostasis, and adrenal insufficiency is a life-threatening condition. Adrenal endocrine activity is maintained through recruitment of subcapsular progenitor cells that follow a unidirectional differentiation path from zona glomerulosa to zona fasciculata (zF). Here, we show that this unidirectionality is ensured by the histone methyltransferase EZH2. Indeed, we demonstrate that EZH2 maintains adrenal steroidogenic cell differentiation by preventing expression of GATA4 and WT1 that cause abnormal dedifferentiation to a progenitor-like state in Ezh2 KO adrenals. EZH2 further ensures normal cortical differentiation by programming cells for optimal response to adrenocorticotrophic hormone (ACTH)/PKA signaling. This is achieved by repression of phosphodiesterases PDE1B, 3A, and 7A and of PRKAR1B. Consequently, EZH2 ablation results in blunted zF differentiation and primary glucocorticoid insufficiency. These data demonstrate an all-encompassing role for EZH2 in programming steroidogenic cells for optimal response to differentiation signals and in maintaining their differentiated state.}, } @article {pmid30541887, year = {2018}, author = {Zheng, T and Zhang, B and Chen, C and Ma, J and Meng, D and Huang, J and Hu, R and Liu, X and Otsu, K and Liu, AC and Li, H and Yin, Z and Huang, G}, title = {Protein kinase p38α signaling in dendritic cells regulates colon inflammation and tumorigenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12313-E12322}, doi = {10.1073/pnas.1814705115}, pmid = {30541887}, issn = {1091-6490}, abstract = {Dendritic cells (DCs) play pivotal roles in maintaining intestinal homeostasis, but how the DCs regulate diverse immune networks on homeostasis breakdown remains largely unknown. Here, we report that, in response to epithelial barrier disruption, colonic DCs regulate the differentiation of type 1 regulatory T (Tr1) cells through p38α-dependent IL-27 production to initiate an effective immune response. Deletion of p38α in DCs, but not in T cells, led to increased Tr1 and protected mice from dextran sodium sulfate-induced acute colitis and chronic colitis-associated colorectal cancer. We show that higher levels of IL-27 in p38α-deficient colonic cDC1s, but not cDC2s, were responsible for the increase of Tr1 cells. Moreover, p38α-dependent IL-27 enhanced IL-22 secretion from intestinal group 3 innate lymphoid cells and protected epithelial barrier function. In p38α-deficient DCs, the TAK1-MKK4/7-JNK-c-Jun axis was hyperactivated, leading to high IL-27 levels, and inhibition of the JNK-c-Jun axis suppressed IL-27 expression. ChIP assay revealed direct binding of c-Jun to the promoter of Il27p28, which was further enhanced in p38α-deficient DCs. In summary, here we identify a key role for p38α signaling in DCs in regulating intestinal inflammatory response and tumorigenesis, and our finding may provide targets for the treatment of inflammatory intestinal diseases.}, } @article {pmid30541886, year = {2018}, author = {O'Brien, E and Salay, LE and Epum, EA and Friedman, KL and Chazin, WJ and Barton, JK}, title = {Yeast require redox switching in DNA primase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13186-13191}, doi = {10.1073/pnas.1810715115}, pmid = {30541886}, issn = {1091-6490}, support = {R35 GM126904/GM/NIGMS NIH HHS/United States ; R01 GM123292/GM/NIGMS NIH HHS/United States ; T32 GM007616/GM/NIGMS NIH HHS/United States ; }, abstract = {Eukaryotic DNA primases contain a [4Fe4S] cluster in the C-terminal domain of the p58 subunit (p58C) that affects substrate affinity but is not required for catalysis. We show that, in yeast primase, the cluster serves as a DNA-mediated redox switch governing DNA binding, just as in human primase. Despite a different structural arrangement of tyrosines to facilitate electron transfer between the DNA substrate and [4Fe4S] cluster, in yeast, mutation of tyrosines Y395 and Y397 alters the same electron transfer chemistry and redox switch. Mutation of conserved tyrosine 395 diminishes the extent of p58C participation in normal redox-switching reactions, whereas mutation of conserved tyrosine 397 causes oxidative cluster degradation to the [3Fe4S]+ species during p58C redox signaling. Switching between oxidized and reduced states in the presence of the Y397 mutations thus puts primase [4Fe4S] cluster integrity and function at risk. Consistent with these observations, we find that yeast tolerate mutations to Y395 in p58C, but the single-residue mutation Y397L in p58C is lethal. Our data thus show that a constellation of tyrosines for protein-DNA electron transfer mediates the redox switch in eukaryotic primases and is required for primase function in vivo.}, } @article {pmid30541885, year = {2018}, author = {Yang, W and Alvarado, A and Glatter, T and Ringgaard, S and Briegel, A}, title = {Baseplate variability of Vibrio cholerae chemoreceptor arrays.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13365-13370}, doi = {10.1073/pnas.1811931115}, pmid = {30541885}, issn = {1091-6490}, abstract = {The chemoreceptor array, a remarkably ordered supramolecular complex, is composed of hexagonally packed trimers of receptor dimers networked by a histidine kinase and one or more coupling proteins. Even though the receptor packing is universal among chemotactic bacteria and archaea, the array architecture has been extensively studied only in selected model organisms. Here, we show that even in the complete absence of the kinase, the cluster II arrays in Vibrio cholerae retain their native spatial localization and the iconic hexagonal packing of the receptors with 12-nm spacing. Our results demonstrate that the chemotaxis array is versatile in composition, a property that allows auxiliary chemotaxis proteins such as ParP and CheV to integrate directly into the assembly. Along with its compositional variability, cluster II arrays exhibit a low degree of structural stability compared with the ultrastable arrays in Escherichia coli We propose that the variability in chemoreceptor arrays is an important mechanism that enables the incorporation of chemotaxis proteins based on their availability.}, } @article {pmid30541619, year = {2018}, author = {Duko, B and Gebrie, M and Deribe, B and Bedaso, A and Ayalew, M}, title = {Patterns of common skin infections among children living with HIV/AIDS in Hawassa City, Ethiopia: a cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {881}, doi = {10.1186/s13104-018-3991-4}, pmid = {30541619}, issn = {1756-0500}, abstract = {OBJECTIVES: Skin disorders are the most common health problems seen among HIV positive patients. It presents with a variety of manifestations which can cause significant morbidity. This study was aimed to assess the prevalence of common skin problems among children living with HIV/AIDS at Hawassa University Comprehensive Specialized Hospital, Hawassa, Ethiopia, 2017/2018. Hospital based cross-sectional study was conducted among 125 children living with HIV/AIDS who were recruited through simple random sampling techniques from February to April 2017. Pre-tested, structured questionnaires were used to collect the data.

RESULT: Among a total of 125 study participants, 72 (57.6%) of the children were males and 97 (77.6%) were in the age range of 10-14 years. 90 (72%) of participants had different kinds of skin problems. Among those who had one kind of common skin infection, 53 (42.4%) were males. Viral skin infections that accounts 48 (53.3%), were the leading cause of skin infections followed by 43 (47.8%), 33(36.7%) and 22 (24.7%) fungal infections, inflammatory and bacterial skin infections respectively. Among all children who were taking ART, only 2.4% of the children had skin related side effects.}, } @article {pmid30541616, year = {2018}, author = {Yoshida, T and Matsumura, K and Tsuchida, A and Hamazaki, K and Inadera, H and , }, title = {Association between cesarean section and constipation in infants: the Japan Environment and Children's Study (JECS).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {882}, doi = {10.1186/s13104-018-3990-5}, pmid = {30541616}, issn = {1756-0500}, abstract = {OBJECTIVE: There have been increasing reports on the association between cesarean section (C-section) and the subsequent development of diseases in infants. C-section affects the diversity of microbiota in the infant's gut. In the present study, we investigated the association between infants delivered by C-section and the development of constipation at 1 year old due to altered gut microbiota using data from the Japan Environment and Children's Study (JECS).

RESULTS: This cohort study (n = 83,019) used data from JECS, an ongoing cohort study which began in January 2011. Data on bowel movement and potential confounding factors were recorded. A log-binomial regression model was used to estimate the risk of C-section, and the results were expressed as risk ratios and their respective 95% confidence intervals. Although infants delivered by C-section were of significantly younger gestational age and lesser birth weight than vaginally delivered infants, the frequency of bowel movements was almost similar between the two, independent of the mode of delivery. The prevalence of constipation in the entire infant was 1.37%. No significant differences were observed for C-section in crude and adjusted risk ratios for constipation.}, } @article {pmid30541615, year = {2018}, author = {Jay, JJ and Sanders, A and Reid, RW and Brouwer, CR}, title = {Connecting nutrition composition measures to biomedical research.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {883}, doi = {10.1186/s13104-018-3997-y}, pmid = {30541615}, issn = {1756-0500}, abstract = {OBJECTIVES: Biomedical research is gaining ground on human disease through many types of "omics", which is leading to increasingly effective treatments and broad applications for precision medicine. The majority of disease treatments still revolve around drugs and biologics. Although food is consumed in much higher quantities, we understand very little about how the human body metabolizes and uses the full range of nutrients, or how these processes affect human health and disease risk. Nutrient composition databases are used by dietitians to describe common consumer food products, but these fail to identify chemicals with the same nomenclature as metabolic pathways in basic life sciences research and with far less precision. Consumer-oriented nutrient compositions often describe generic substances (e.g. Sugars) while scientific reporting is often much more specific (e.g. Dextrose, Fructose, etc.). Integrating these two fields of research presents a difficult challenge for novel applications of precision nutrition.

DATA DESCRIPTION: This data set provides a manually curated collection of nutrient identifiers from the USDA's Nutrition Data Bases and maps them to PubChem (a resource for cheminformatics and drug discovery research), biomedical literature records in PubMed using Medical Subject Headings, biological pathways using the Chemical Entities of Biological Interest ontology.}, } @article {pmid30541452, year = {2018}, author = {Ma, Z and Zhu, H and Su, Y and Meng, Y and Lin, H and He, K and Fan, H}, title = {Screening of Streptococcus Suis serotype 2 resistance genes with GWAS and transcriptomic microarray analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {907}, doi = {10.1186/s12864-018-5339-9}, pmid = {30541452}, issn = {1471-2164}, support = {2014ZX0800946B//the National Transgenic Major Program/ ; 31772746, 31302093, 31272581//the National Natural Science Foundation of China/ ; 2016YFD0501607//the National Key Research and Development Program/ ; 201403054//Special Fund for Agro-scientific Research in the Public Interest/ ; BK20130676//the Natural Science Foundation of Jiangsu Province/ ; KYZ201630//the Key Project of Independent Innovation of the Fundamental Research Fund for the Central Universities of Nanjing Agricultural University/ ; BE2013433//the Jiangsu Province Science and Technology Support Program/ ; PAPD//the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; 201706855039//China Scholarship Council/ ; }, abstract = {BACKGROUND: Swine streptococcosis has caused great economic loss in the swine industry, and the major pathogen responsible for this disease is Streptococcus Suis serotype 2 (SS2). Disease resistance breeding is a fundamental way of resolving this problem. With the development of GWAS and transcriptomic microarray technology, we now have powerful research tools to identify SS2 resistance genes.

RESULTS: In this research, we generated an F2 generation of SS2 resistant C57BL/6 and SS2 susceptive A/J mice. With the F2 generation of these two mice strains and GWAS analysis, we identified 286 significant mouse genome SNPs sites associated with the SS2 resistance trait. Gene expression profiles for C57BL/6 and A/J were analyzed under SS2 infection pressure by microarray. In total, 251 differentially expressed genes were identified between these two mouse strains during SS2 infection. After combining the GWAS and gene expression profile data, we located two genes that were significantly associated with SS2 resistance, which were the UBA domain containing 1 gene (Ubac1) and Epsin 1 gene (Epn 1). GO classification and over-representation analysis revealed nine up-regulated related to immune function, which could potentially be involved in the C57BL/6 SS2 resistance trait.

CONCLUSION: This is the first study to use both SNP chip and gene express profile chip for SS2 resistance gene identification in mouse, and these results will contribute to swine SS2 resistance breeding.}, } @article {pmid30541451, year = {2018}, author = {Yu, X and Kimball, JA and Milla-Lewis, SR}, title = {High density genetic maps of St. Augustinegrass and applications to comparative genomic analysis and QTL mapping for turf quality traits.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {346}, doi = {10.1186/s12870-018-1554-4}, pmid = {30541451}, issn = {1471-2229}, support = {2015-51181-24291//USDA National Institute of Food and Agriculture/ ; }, mesh = {Chromosome Mapping ; Genes, Plant/genetics ; Genetic Markers/genetics ; Genomics ; Genotyping Techniques ; Poaceae/anatomy & histology/*genetics ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/*genetics ; Quantitative Trait, Heritable ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: St. Augustinegrass [Stenotaphrum secundatum (Walt.) Kuntze] is a warm-season, perennial turfgrass species well adapted for home lawns and commercial landscapes with economic and ecological value. However, a lack of genomic resources in St. Augustinegrass has hindered the full utilization of genetic variance for maximizing genetic gain and limited our understanding of the species' evolution.

RESULTS: In this study, we constructed the first high-density linkage map for St. Augustinegrass using a genotyping by sequencing (GBS) approach. The integrated linkage map consists of 2871 single nucleotide polymorphism (SNP) and 81 simple sequence repeat (SSR) markers, spanning 1241.7 cM, with an average distance of 0.4 cM between markers, and thus represents the densest genetic map for St. Augustinegrass to date. Comparative genomic analysis revealed inter-chromosome arrangements and independent nested chromosome fusion events that occurred after St. Augustinegrass, foxtail millet, sorghum, and rice diverged from a common ancestor. Forty-eight candidate quantitative trait loci (QTL) were detected for turf quality-related traits, including overall turf quality, leaf texture, genetic color, and turf density. Three hot spot regions were identified on linkage groups LG3 and LG8, where multi-QTL for different traits overlapped. Several leaf development related genes were contained within these identified QTL regions.

CONCLUSIONS: This study developed the first high-density genetic map and identified putative QTL related to turf quality, which provide valuable genetic resources for marker-assisted selection (MAS) in St. Augustinegrass.}, } @article {pmid30541450, year = {2018}, author = {Whisner, CM and Maldonado, J and Dente, B and Krajmalnik-Brown, R and Bruening, M}, title = {Diet, physical activity and screen time but not body mass index are associated with the gut microbiome of a diverse cohort of college students living in university housing: a cross-sectional study.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {210}, doi = {10.1186/s12866-018-1362-x}, pmid = {30541450}, issn = {1471-2180}, support = {DP5 OD017910/OD/NIH HHS/United States ; R01 DK090379/DK/NIDDK NIH HHS/United States ; R01 DK105829/DK/NIDDK NIH HHS/United States ; 1DP5OD017910//National Institutes of Health/ ; }, abstract = {BACKGROUND: Modifiable lifestyle factors (e.g. dietary intake and physical activity) are important contributors to weight gain during college. The purpose of this study was to evaluate whether associations exist between body mass index, physical activity, screen time, dietary consumption (fat, protein, carbohydrates, and fiber), and gut microbial diversity during the first year of college. Racially/ethnically diverse college students (n = 82; 61.0% non-white) at a large Southwestern university completed self-reported physical activity and 24-h recall dietary assessments, height and weight measurements, and provided one fecal sample for gut microbiome analysis. Fecal microbial community composition was assessed with Illumina MiSeq next-generation sequencing of PCR amplified 16S rRNA genes. Post-hoc analyses compared microbial diversity by groups of high and low physical activity and fiber intake using QIIME and LEfSe bioinformatics software.

RESULTS: No statistically significant differences were observed between body mass index and gut microbiome abundance and diversity. Median daily consumption of dietary fiber was 11.2 (7.6, 14.9) g/d, while the median self-reported moderate-to-vigorous physical activity (MVPA) was 55.7 (27.9, 79.3) min/d and screen time 195.0 (195.0, 315.0) min/d. Microbial analysis by LEfSe identified Paraprevotellaceae, Lachnospiraceae, and Lachnospira as important phylotypes in college students reporting greater MVPA, while Enterobacteriaceae and Enterobacteriales were more enriched among students reporting less MVPA (p < 0.05). Barnesiellaceae, Alphaproteobacteria, and Ruminococcus were more abundant taxa among those consuming less than the median fiber intake (p < 0.05). Post-hoc analyses comparing weighted UniFrac distance metrics based on combined categories of high and low MVPA and fiber revealed that clustering distances between members of the high MVPA-low fiber group were significantly smaller when compared to distances between members of all other MVPA-fiber groups (p < 0.0001).

CONCLUSIONS: Habitual fiber consumption and MVPA behaviors help explain the differential abundance of specific microbial taxa and overall gut microbial diversity differences in first-year college students.}, } @article {pmid30541448, year = {2018}, author = {Rogier, O and Chateigner, A and Amanzougarene, S and Lesage-Descauses, MC and Balzergue, S and Brunaud, V and Caius, J and Soubigou-Taconnat, L and Jorge, V and Segura, V}, title = {Accuracy of RNAseq based SNP discovery and genotyping in Populusnigra.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {909}, doi = {10.1186/s12864-018-5239-z}, pmid = {30541448}, issn = {1471-2164}, support = {ANR-13-JSV6-0001//Agence Nationale de la Recherche/ ; ANR-10-LABX-0040-SPS//Agence Nationale de la Recherche/ ; }, abstract = {BACKGROUD: Populus nigra is a major tree species of ecological and economic importance for which several initiatives have been set up to create genomic resources. In order to access the large number of Single Nucleotide Polymorphisms (SNPs) typically needed to carry out a genome scan, the present study aimed at evaluating RNA sequencing as a tool to discover and type SNPs in genes within natural populations of P. nigra.

RESULTS: We have devised a bioinformatics pipeline to call and type SNPs from RNAseq reads and applied it to P. nigra transcriptomic data. The accuracy of the resulting RNAseq-based SNP calling and typing has been evaluated by (i) comparing their position and alleles to those previously reported in candidate genes, (ii) assessing their genotyping accuracy with respect to a previously available SNP chip and (iii) evaluating their inter-annual repeatability. We found that a combination of several callers yields a good compromise between the number of variants type and the accuracy of genotyping. We further used the resulting genotypic data to carry out basic genetic analyses whose results confirm the quality of the RNAseq-based SNP dataset.

CONCLUSIONS: We demonstrated the potential and accuracy of RNAseq as an efficient way to genotype SNPs in P. nigra. These results open prospects towards the use of this technology for quantitative and population genomics studies.}, } @article {pmid30541446, year = {2018}, author = {Liu, J and Moyankova, D and Lin, CT and Mladenov, P and Sun, RZ and Djilianov, D and Deng, X}, title = {Transcriptome reprogramming during severe dehydration contributes to physiological and metabolic changes in the resurrection plant Haberlea rhodopensis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {351}, doi = {10.1186/s12870-018-1566-0}, pmid = {30541446}, issn = {1471-2229}, support = {14-10//China-Bulgaria's Inter-Governmental S&T Cooperation committee/ ; DNTS/China/01/7//Bulgarian Science Fund/ ; }, mesh = {Dehydration ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Lamiales/*genetics/metabolism/physiology ; Transcriptome ; }, abstract = {BACKGROUND: Water shortage is a major factor that harms agriculture and ecosystems worldwide. Plants display various levels of tolerance to water deficit, but only resurrection plants can survive full desiccation of their vegetative tissues. Haberlea rhodopensis, an endemic plant of the Balkans, is one of the few resurrection plants found in Europe. We performed transcriptomic analyses of this species under slight, severe and full dehydration and recovery to investigate the dynamics of gene expression and associate them with existing physiological and metabolomics data.

RESULTS: De novo assembly yielded a total of 142,479 unigenes with an average sequence length of 1034 nt. Among them, 18,110 unigenes were differentially expressed. Hierarchical clustering of all differentially expressed genes resulted in seven clusters of dynamic expression patterns. The most significant expression changes, involving more than 15,000 genes, started at severe dehydration (~ 20% relative water content) and were partially maintained at full desiccation (< 10% relative water content). More than a hundred pathways were enriched and functionally organized in a GO/pathway network at the severe dehydration stage. Transcriptomic changes in key pathways were analyzed and discussed in relation to metabolic processes, signal transduction, quality control of protein and DNA repair in this plant during dehydration and rehydration.

CONCLUSION: Reprograming of the transcriptome occurs during severe dehydration, resulting in a profound alteration of metabolism toward alternative energy supply, hormone signal transduction, and prevention of DNA/protein damage under very low cellular water content, underlying the observed physiological and metabolic responses and the resurrection behavior of H. rhodopensis.}, } @article {pmid30541445, year = {2018}, author = {Chen, K and Luan, M and Xiong, H and Chen, P and Chen, J and Gao, G and Huang, K and Zhu, A and Yu, C}, title = {Genome-wide association study discovered favorable single nucleotide polymorphisms and candidate genes associated with ramet number in ramie (Boehmeria nivea L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {345}, doi = {10.1186/s12870-018-1573-1}, pmid = {30541445}, issn = {1471-2229}, support = {CAAS-ASTIP-2016-IBFC04//Chinese Academy of Agricultural Sciences/ ; CARS-19-E02//Chinese Academy of Agricultural Sciences/ ; 31801413//National Natural Science Foundation of China/ ; }, mesh = {Boehmeria/*genetics/physiology ; Genes, Plant/*genetics/physiology ; Genome-Wide Association Study ; Genotyping Techniques ; Polymorphism, Single Nucleotide/*genetics ; Quantitative Trait, Heritable ; }, abstract = {BACKGROUND: Ramie (Boehmeria nivea L.) is one of the most important natural fiber crops and an important forage grass in south China. Ramet number, which is a quantitative trait controlled by multigenes, is one of the most important agronomic traits in plants because the ramet number per plant is a key component of grain yield and biomass. However, the genetic variation and genetic architecture of ramie ramet number are rarely known.

RESULTS: A genome-wide association study was performed using a panel of 112 core germplasms and 108,888 single nucleotide polymorphisms (SNPs) detected using specific-locus amplified fragment sequencing technology. Trait-SNP association analysis detected 44 significant SNPs that were associated with ramet number at P < 0.01. The favorable SNP Marker20170-64 emerged at least twice in the three detected stages and was validated to be associated with the ramie ramet number using genomic DNA polymerase chain reaction with an F1 hybrid progeny population. Comparative genome analysis predicted nine candidate genes for ramet number based on Marker20170-64. Real-time quantitative polymerase chain reaction analysis indicated that six of the genes were specific to upregulation in the ramie variety with high ramet number. These results suggest that these genes could be considered as ramet number-associated candidates in ramie.

CONCLUSIONS: The identified loci or genes may be promising targets for genetic engineering and selection for modulating the ramet number in ramie. Our work improves understanding of the genetics of ramet number in ramie core germplasms and provides tools for marker-assisted selection for improvement of agricultural traits.}, } @article {pmid30541444, year = {2018}, author = {Li, Y and Li, X and Fu, D and Wu, C}, title = {Panicle Morphology Mutant 1 (PMM1) determines the inflorescence architecture of rice by controlling brassinosteroid biosynthesis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {348}, doi = {10.1186/s12870-018-1577-x}, pmid = {30541444}, issn = {1471-2229}, support = {31630054//National Natural Science Foundation of China/ ; 31425018//National Natural Science Foundation of China/ ; 31821005//National Natural Science Foundation of China/ ; 054//Program for Chinese Outstanding Talents in Agricultural Scientific Research/ ; 25//Program for New Century Excellent Talents in University (CN)/ ; }, mesh = {Brassinosteroids/*biosynthesis ; Cloning, Molecular ; Flowers/*genetics/growth & development/metabolism/ultrastructure ; Gene Expression Regulation, Plant ; Microscopy, Electron, Scanning ; Oryza/*genetics/growth & development/metabolism/ultrastructure ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; }, abstract = {BACKGROUND: Panicle architecture is one of the main important agronomical traits that determine branch number and grain number in rice. Although a large number of genes involved in panicle development have been identified in recent years, the complex processes of inflorescence patterning need to be further characterized in rice. Brassinosteroids (BRs) are a class of steroid phytohormones. A great understanding of how BRs contribute to plant height and leaf erectness have been reported, however, the molecular and genetic mechanisms of panicle architecture influenced by BRs remain unclear.

RESULTS: Here, we identified PMM1, encoding a cytochrome P450 protein involved in BRs biosynthesis, and characterized its role in panicle architecture in rice. Three alleles of pmm1 were identified from our T-DNA insertional mutant library. Map-based cloning revealed that a large fragment deletion from the 2nd to 9th exons of PMM1 was responsible for the clustered primary branch morphology in pmm1-1. PMM1 is a new allele of DWARF11 (D11) PMM1 transcripts are preferentially expressed in young panicles, particularly expressed in the primordia of branches and spikelets during inflorescence development. Furthermore, overexpression of OsDWARF4 (D4), another gene encoding cytochrome P450, completely rescued the abnormal panicle phenotype of pmm1-1. Overall, it can be concluded that PMM1 is an important gene involved in BRs biosynthesis and affecting the differentiation of spikelet primordia and patterns of panicle branches in rice.

CONCLUSIONS: PMM1 is a new allele of D11, which encodes a cytochrome P450 protein involved in BRs biosynthesis pathway. Overexpression of D4 could successfully rescue the abnormal panicle architecture of pmm1 plants, indicating that PMM1/D11 and D4 function redundantly in BRs biosynthesis. Thus, our results demonstrated that PMM1 determines the inflorescence architecture by controlling brassinosteroid biosynthesis in rice.}, } @article {pmid30541441, year = {2018}, author = {Zhu, J and Guo, Y and Su, K and Liu, Z and Ren, Z and Li, K and Guo, X}, title = {Construction of a highly saturated Genetic Map for Vitis by Next-generation Restriction Site-associated DNA Sequencing.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {347}, doi = {10.1186/s12870-018-1575-z}, pmid = {30541441}, issn = {1471-2229}, support = {31372021, 31572085//National Natural Science Foundation of China/ ; }, mesh = {*Chromosome Mapping/methods ; Chromosomes, Plant/genetics ; Genes, Plant/*genetics ; Genetic Markers/genetics ; High-Throughput Nucleotide Sequencing/methods ; Metagenomics ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait, Heritable ; Restriction Mapping/*methods ; Vitis/*genetics ; }, abstract = {BACKGROUND: High-saturate molecular linkage maps are an important tool in studies on plant molecular biology and assisted breeding. Development of a large set of single nucleotide polymorphisms (SNPs) via next-generation sequencing (NGS)-based methods, restriction-site associated DNA sequencing (RAD-seq), and the generation of a highly saturated genetic map help improve fine mapping of quantitative trait loci (QTL).

RESULTS: We generated a highly saturated genetic map to identify significant traits in two elite grape cultivars and 176 F1 plants. In total, 1,426,967 high-quality restriction site-associated DNA tags were detected; 51,365, 23,683, and 70,061 markers were assessed in 19 linkage groups (LGs) for the maternal, paternal, and integrated maps, respectively. Our map was highly saturated in terms of marker density and average "Gap ≤ 5 cM" percentage.

CONCLUSIONS: In this study, RAD-seq of 176 F1 plants and their parents yielded 8,481,484 SNPs and 1,646,131 InDel markers, of which 65,229 and 4832, respectively, were used to construct a highly saturated genetic map for grapevine. This map is expected to facilitate genetic studies on grapevine, including an evaluation of grapevine and deciphering the genetic basis of economically and agronomically important traits. Our findings provide basic essential genetic data the grapevine genetic research community, which will lead to improvements in grapevine breeding.}, } @article {pmid30541440, year = {2018}, author = {Yu, D and Qanmber, G and Lu, L and Wang, L and Li, J and Yang, Z and Liu, Z and Li, Y and Chen, Q and Mendu, V and Li, F and Yang, Z}, title = {Genome-wide analysis of cotton GH3 subfamily II reveals functional divergence in fiber development, hormone response and plant architecture.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {350}, doi = {10.1186/s12870-018-1545-5}, pmid = {30541440}, issn = {1471-2229}, support = {31621005//the Funds for Creative Research Groups of China/ ; }, mesh = {*Cotton Fiber ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/*genetics/physiology ; Genome-Wide Association Study ; Gossypium/anatomy & histology/*genetics/growth & development/metabolism ; Indoleacetic Acids/*metabolism ; Phylogeny ; Plant Growth Regulators/*metabolism ; Plant Proteins/*genetics/metabolism/physiology ; }, abstract = {BACKGROUND: Auxin-induced genes regulate many aspects of plant growth and development. The Gretchen Hagen 3 (GH3) gene family, one of three major early auxin-responsive families, is ubiquitous in the plant kingdom and its members function as regulators in modulating hormonal homeostasis, and stress adaptations. Specific Auxin-amido synthetase activity of GH3 subfamily II genes is reported to reversibly inactivate or fully degrade excess auxin through the formation of amino acid conjugates. Despite these crucial roles, to date, genome-wide analysis of the GH3 gene family has not been reported in cotton.

RESULTS: We identified a total of 10 GH3 subfamily II genes in G. arboreum, 10 in G. raimondii, and 20 in G. hirsutum, respectively. Bioinformatic analysis showed that cotton GH3 genes are conserved with the established GH3s in plants. Expression pattern analysis based on RNA-seq data and qRT-PCR revealed that 20 GhGH3 genes were differentially expressed in a temporally and spatially specific manner, indicating their diverse functions in growth and development. We further summarized the organization of promoter regulatory elements and monitored their responsiveness to treatment with IAA (indole-3-acetic acid), SA (salicylic acid), GA (gibberellic acid) and BL (brassinolide) by qRT-PCR in roots and stems. These hormones seemed to regulate the expression of GH3 genes in both a positive and a negative manner while certain members likely have higher sensitivity to all four hormones. Further, we tested the expression of GhGH3 genes in the BR-deficient mutant pag1 and the corresponding wild-type (WT) of CCRI24. The altered expression reflected the true responsiveness to BL and further suggested possible reasons, at least in part, responsible for the dramatic dwarf and shriveled phenotypes of pag1.

CONCLUSION: We comprehensively identified GH3 subfamily II genes in cotton. GhGH3s are differentially expressed in various tissues/organs/stages. Their response to IAA, SA, BL and GA and altered expression in pag1 suggest that some GhGH3 genes might be simultaneously involved in multiple hormone signaling pathways. Taken together, our results suggest that members of the GhGH3 gene family could be possible candidate genes for mechanistic study and applications in cotton fiber development in addition to the reconstruction of plant architecture.}, } @article {pmid30541439, year = {2018}, author = {Oki, K and Akiyama, T and Matsuda, K and Gawad, A and Makino, H and Ishikawa, E and Oishi, K and Kushiro, A and Fujimoto, J}, title = {Long-term colonization exceeding six years from early infancy of Bifidobacterium longum subsp. longum in human gut.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {209}, doi = {10.1186/s12866-018-1358-6}, pmid = {30541439}, issn = {1471-2180}, abstract = {BACKGROUND: The importance of the gut microbiota at the early stage of life and their longitudinal effect on host health have recently been well investigated. In particular, Bifidobacterium longum subsp. longum, a common component of infant gut microbiota, appears in the gut shortly after birth and can be detected there throughout an individual's lifespan. However, it remains unclear whether this species colonizes in the gut over the long term from early infancy. Here, we investigated the long-term colonization of B. longum subsp. longum by comparing the genotypes of isolates obtained at different time points from individual subjects. Strains were isolated over time from the feces of 12 subjects followed from early infancy (the first six months of life) up to childhood (approximately six years of age). We also considered whether the strains were transmitted from their mothers' perinatal samples (prenatal feces and postnatal breast milk).

RESULTS: Intra-species diversity of B. longum subsp. longum was observed in some subjects' fecal samples collected in early infancy and childhood, as well as in the prenatal fecal samples of their mothers. Among the highlighted strains, several were confirmed to colonize and persist in single individuals from as early as 90 days of age for more than six years; these were classified as long-term colonizers. One of the long-term colonizers was also detected from the corresponding mother's postnatal breast milk. Quantitative polymerase chain reaction data suggested that these long-term colonizers persisted in the subjects' gut despite the existence of the other predominant species of Bifidobacterium.

CONCLUSIONS: Our results showed that several strains belonging to B. longum subsp. longum colonized in the human gut from early infancy through more than six years, confirming the existence of long-term colonizers from this period. Moreover, the results suggested that these strains persisted in the subjects' gut while co-existing with the other predominant bifidobacterial species. Our findings also suggested the importance of microbial-strain colonization in early infancy relative to their succession and showed the possibility that probiotics targeting infants might have longitudinal effects.

TRIAL REGISTRATION: TRN: ISRCTN25216339 . Date of registration: 11/03/2016. Prospectively registered.}, } @article {pmid30541438, year = {2018}, author = {Catanese, HN and Brayton, KA and Gebremedhin, AH}, title = {A nearest-neighbors network model for sequence data reveals new insight into genotype distribution of a pathogen.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {475}, doi = {10.1186/s12859-018-2453-2}, pmid = {30541438}, issn = {1471-2105}, support = {IIS-1553528//Directorate for Computer and Information Science and Engineering/ ; }, mesh = {Amino Acid Sequence/*genetics ; Cluster Analysis ; Genotype ; Network Meta-Analysis ; Proteins/*chemistry ; }, abstract = {BACKGROUND: Sequence similarity networks are useful for classifying and characterizing biologically important proteins. Threshold-based approaches to similarity network construction using exact distance measures are prohibitively slow to compute and rely on the difficult task of selecting an appropriate threshold, while similarity networks based on approximate distance calculations compromise useful structural information.

RESULTS: We present an alternative network representation for a set of sequence data that overcomes these drawbacks. In our model, called the Directed Weighted All Nearest Neighbors (DiWANN) network, each sequence is represented by a node and is connected via a directed edge to only the closest sequence, or sequences in the case of ties, in the dataset. Our contributions span several aspects. Specifically, we: (i) Apply an all nearest neighbors network model to protein sequence data from three different applications and examine the structural properties of the networks; (ii) Compare the model against threshold-based networks to validate their semantic equivalence, and demonstrate the relative advantages the model offers; (iii) Demonstrate the model's resilience to missing sequences; and (iv) Develop an efficient algorithm for constructing a DiWANN network from a set of sequences. We find that the DiWANN network representation attains similar semantic properties to threshold-based graphs, while avoiding weaknesses of both high and low threshold graphs. Additionally, we find that approximate distance networks, using BLAST bitscores in place of exact edit distances, can cause significant loss of structural information. We show that the proposed DiWANN network construction algorithm provides a fourfold speedup over a standard threshold based approach to network construction. We also identify a relationship between the centrality of a sequence in a similarity network of an Anaplasma marginale short sequence repeat dataset and how broadly that sequence is dispersed geographically.

CONCLUSION: We demonstrate that using approximate distance measures to rapidly construct similarity networks may lead to significant deficiencies in the structure of that network in terms centrality and clustering analyses. We present a new network representation that maintains the structural semantics of threshold-based networks while increasing connectedness, and an algorithm for constructing the network using exact distance measures in a fraction of the time it would take to build a threshold-based equivalent.}, } @article {pmid30541436, year = {2018}, author = {Chan, AW and Williams, AL and Jannink, JL}, title = {A statistical framework for detecting mislabeled and contaminated samples using shallow-depth sequence data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {478}, doi = {10.1186/s12859-018-2512-8}, pmid = {30541436}, issn = {1471-2105}, support = {OPP1048542//Bill and Melinda Gates Foundation/ ; }, mesh = {Databases, Nucleic Acid/*standards ; Humans ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Researchers typically sequence a given individual multiple times, either re-sequencing the same DNA sample (technical replication) or sequencing different DNA samples collected on the same individual (biological replication) or both. Before merging the data from these replicate sequence runs, it is important to verify that no errors, such as DNA contamination or mix-ups, occurred during the data collection pipeline. Methods to detect such errors exist but are often ad hoc, cannot handle missing data and several require phased data. Because they require some combination of genotype calling, imputation, and haplotype phasing, these methods are unsuitable for error detection in low- to moderate-depth sequence data where such tasks are difficult to perform accurately. Additionally, because most existing methods employ a pairwise-comparison approach for error detection rather than joint analysis of the putative replicates, results may be difficult to interpret.

RESULTS: We introduce a new method for error detection suitable for shallow-, moderate-, and high-depth sequence data. Using Bayes Theorem, we calculate the posterior probability distribution over the set of relations describing the putative replicates and infer which of the samples originated from an identical genotypic source.

CONCLUSIONS: Our method addresses key limitations of existing approaches and produced highly accurate results in simulation experiments. Our method is implemented as an R package called BIGRED (Bayes Inferred Genotype Replicate Error Detector), which is freely available for download: https://github.com/ac2278/BIGRED .}, } @article {pmid30541432, year = {2018}, author = {Li, C and Zhao, T and Yu, H and Li, C and Deng, X and Dong, Y and Zhang, F and Zhang, Y and Mei, L and Chen, J and Zhu, S}, title = {Genetic basis of heterosis for yield and yield components explored by QTL mapping across four genetic populations in upland cotton.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {910}, doi = {10.1186/s12864-018-5289-2}, pmid = {30541432}, issn = {1471-2164}, support = {31501342//The National Natural Science Fund/ ; 2013AA102601//National High Technology Research and Development Program of China/ ; 2016YFD0101404//The National Key Technology R&D program of China/ ; CARS-18-25//China Agriculture Research System/ ; }, abstract = {BACKGROUND: Quantitative trait loci (QTL) mapping provides a powerful tool to unravel the genetic bases of cotton yield and its components, as well as their heterosis. In the present study, the genetic basis underlying inbreeding depression and heterosis for yield and yield components of upland cotton was investigated in recombinant inbred line (RIL), immortalized F2 (IF2), and two backcross (BCF1) populations based on a high-density SNP linkage map across four environments.

RESULTS: Significant inbreeding depression of fruit branches per plant (FB), boll numbers per plant (BN), seed cotton yield (SY), and lint yield (LY) in RIL population and high levels of heterosis for SY, LY, and boll weight (BW) in IF2 and two BCF1 populations were observed. A total of 285 QTLs were identified in the four related populations using a composite interval mapping approach. In the IF2 population, 26.60% partially dominant (PD) QTLs and 71.28% over-dominant (OD) QTLs were identified. In two BCF1 populations, 42.41% additive QTLs, 4.19% PD QTLs, and 53.40% OD QTLs were detected. For multi-environment analysis, phenotypic variances (PV) explained by e-QTLs were higher than those by m-QTLs in each of the populations, and the average PV of m-QTLs and e-QTLs explained by QTL × environment interactions occupied a considerable proportion of total PV in all seven datasets.

CONCLUSIONS: At the single-locus level, the genetic bases of heterosis varied in different populations. Partial dominance and over-dominance were the main cause of heterosis in the IF2 population, while additive effects and over-dominance were the main genetic bases of heterosis in two BCF1 populations. In addition, the various genetic components to heterosis presented trait specificity. In the multi-environment model analysis, epistasis was a common feature of most loci associated with inbreeding depression and heterosis. Furthermore, the environment was a critical factor in the expression of these m-QTLs and e-QTLs. Altogether, additive effects, over-dominance, epistasis and environmental interactions all contributed to the heterosis of yield and its components in upland cotton, with over-dominance and epistasis more important than the others.}, } @article {pmid30541431, year = {2018}, author = {Musacchia, F and Ciolfi, A and Mutarelli, M and Bruselles, A and Castello, R and Pinelli, M and Basu, S and Banfi, S and Casari, G and Tartaglia, M and Nigro, V and , }, title = {VarGenius executes cohort-level DNA-seq variant calling and annotation and allows to manage the resulting data through a PostgreSQL database.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {477}, doi = {10.1186/s12859-018-2532-4}, pmid = {30541431}, issn = {1471-2105}, support = {GSP15001//Fondazione Telethon/ ; }, mesh = {Computational Biology/*methods ; Databases, Factual ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Targeted resequencing has become the most used and cost-effective approach for identifying causative mutations of Mendelian diseases both for diagnostics and research purposes. Due to very rapid technological progress, NGS laboratories are expanding their capabilities to address the increasing number of analyses. Several open source tools are available to build a generic variant calling pipeline, but a tool able to simultaneously execute multiple analyses, organize, and categorize the samples is still missing.

RESULTS: Here we describe VarGenius, a Linux based command line software able to execute customizable pipelines for the analysis of multiple targeted resequencing data using parallel computing. VarGenius provides a database to store the output of the analysis (calling quality statistics, variant annotations, internal allelic variant frequencies) and sample information (personal data, genotypes, phenotypes). VarGenius can also perform the "joint analysis" of hundreds of samples with a single command, drastically reducing the time for the configuration and execution of the analysis. VarGenius executes the standard pipeline of the Genome Analysis Tool-Kit (GATK) best practices (GBP) for germinal variant calling, annotates the variants using Annovar, and generates a user-friendly output displaying the results through a web page. VarGenius has been tested on a parallel computing cluster with 52 machines with 120GB of RAM each. Under this configuration, a 50 M whole exome sequencing (WES) analysis for a family was executed in about 7 h (trio or quartet); a joint analysis of 30 WES in about 24 h and the parallel analysis of 34 single samples from a 1 M panel in about 2 h.

CONCLUSIONS: We developed VarGenius, a "master" tool that faces the increasing demand of heterogeneous NGS analyses and allows maximum flexibility for downstream analyses. It paves the way to a different kind of analysis, centered on cohorts rather than on singleton. Patient and variant information are stored into the database and any output file can be accessed programmatically. VarGenius can be used for routine analyses by biomedical researchers with basic Linux skills providing additional flexibility for computational biologists to develop their own algorithms for the comparison and analysis of data. The software is freely available at: https://github.com/frankMusacchia/VarGenius.}, } @article {pmid30541430, year = {2018}, author = {Kim, H and Han, S and Um, JH and Park, K}, title = {Accelerating a cross-correlation score function to search modifications using a single GPU.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {480}, doi = {10.1186/s12859-018-2559-6}, pmid = {30541430}, issn = {1471-2105}, mesh = {Algorithms ; Peptides/*chemistry ; Software/*standards ; }, abstract = {BACKGROUND: A cross-correlation (XCorr) score function is one of the most popular score functions utilized to search peptide identifications in databases, and many computer programs, such as SEQUEST, Comet, and Tide, currently use this score function. Recently, the HiXCorr algorithm was developed to speed up this score function for high-resolution spectra by improving the preprocessing step of the tandem mass spectra. However, despite the development of the HiXCorr algorithm, the score function is still slow because candidate peptides increase when post-translational modifications (PTMs) are considered in the search.

RESULTS: We used a graphics processing unit (GPU) to develop the accelerating score function derived by combining Tide's XCorr score function and the HiXCorr algorithm. Our method is 2.7 and 5.8 times faster than the original Tide and Tide-Hi, respectively, for 50 Da precursor tolerance. Our GPU-based method produced identical scores as did the CPU-based Tide and Tide-Hi.

CONCLUSION: We propose the accelerating score function to search modifications using a single GPU. The software is available at https://github.com/Tide-for-PTM-search/Tide-for-PTM-search .}, } @article {pmid30541428, year = {2018}, author = {Frost, HR and Amos, CI}, title = {A multi-omics approach for identifying important pathways and genes in human cancer.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {479}, doi = {10.1186/s12859-018-2476-8}, pmid = {30541428}, issn = {1471-2105}, support = {U19 CA148127/CA/NCI NIH HHS/United States ; P20 GM103534/GM/NIGMS NIH HHS/United States ; P30CA023108//National Institutes of Health/ ; P20GM103534//National Institutes of Health (US)/ ; K01 LM012426/LM/NLM NIH HHS/United States ; P30 CA023108/CA/NCI NIH HHS/United States ; U19CA148127//National Institutes of Health/ ; U01CA196386//National Institutes of Health/ ; U01 CA196386/CA/NCI NIH HHS/United States ; K01LM012426//National Institutes of Health/ ; }, mesh = {Genomics/*methods ; Humans ; Neoplasms/*genetics/pathology ; }, abstract = {BACKGROUND: Cancer develops when pathways controlling cell survival, cell fate or genome maintenance are disrupted by the somatic alteration of key driver genes. Understanding how pathway disruption is driven by somatic alterations is thus essential for an accurate characterization of cancer biology and identification of therapeutic targets. Unfortunately, current cancer pathway analysis methods fail to fully model the relationship between somatic alterations and pathway activity.

RESULTS: To address these limitations, we developed a multi-omics method for identifying biologically important pathways and genes in human cancer. Our approach combines single-sample pathway analysis with multi-stage, lasso-penalized regression to find pathways whose gene expression can be explained largely in terms of gene-level somatic alterations in the tumor. Importantly, this method can analyze case-only data sets, does not require information regarding pathway topology and supports personalized pathway analysis using just somatic alteration data for a limited number of cancer-associated genes. The practical effectiveness of this technique is illustrated through an analysis of data from The Cancer Genome Atlas using gene sets from the Molecular Signatures Database.

CONCLUSIONS: Novel insights into the pathophysiology of human cancer can be obtained from statistical models that predict expression-based pathway activity in terms of non-silent somatic mutations and copy number variation. These models enable the identification of biologically important pathways and genes and support personalized pathway analysis in cases where gene expression data is unavailable.}, } @article {pmid30541427, year = {2018}, author = {Rosa, MTG and Almeida, DM and Pires, IS and da Rosa Farias, D and Martins, AG and da Maia, LC and de Oliveira, AC and Saibo, NJM and Oliveira, MM and Abreu, IA}, title = {Insights into the transcriptional and post-transcriptional regulation of the rice SUMOylation machinery and into the role of two rice SUMO proteases.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {349}, doi = {10.1186/s12870-018-1547-3}, pmid = {30541427}, issn = {1471-2229}, support = {SFRH/BD/84219/2012//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/65229/2009//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/68835/2010//Fundação para a Ciência e a Tecnologia/ ; IF/01126/2012//Fundação para a Ciência e a Tecnologia/ ; IF/00764/2014//Fundação para a Ciência e a Tecnologia/ ; UID/Multi/04551/2013//Fundação para a Ciência e a Tecnologia/ ; 477083/2013-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {*Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics ; Oryza/enzymology/genetics/*metabolism ; Peptide Hydrolases/metabolism ; Phylogeny ; Plant Proteins/genetics ; SUMO-1 Protein/genetics ; *Sumoylation/genetics ; }, abstract = {BACKGROUND: SUMOylation is an essential eukaryotic post-translation modification that, in plants, regulates numerous cellular processes, ranging from seed development to stress response. Using rice as a model crop plant, we searched for potential regulatory points that may influence the activity of the rice SUMOylation machinery genes.

RESULTS: We analyzed the presence of putative cis-acting regulatory elements (CREs) within the promoter regions of the rice SUMOylation machinery genes and found CREs related to different cellular processes, including hormone signaling. We confirmed that the transcript levels of genes involved in target-SUMOylation, containing ABA- and GA-related CREs, are responsive to treatments with these hormones. Transcriptional analysis in Nipponbare (spp. japonica) and LC-93-4 (spp. indica), showed that the transcript levels of all studied genes are maintained in the two subspecies, under normal growth. OsSUMO3 is an exceptional case since it is expressed at low levels or is not detectable at all in LC-93-4 roots and shoots, respectively. We revealed post-transcriptional regulation by alternative splicing (AS) for all genes studied, except for SUMO coding genes, OsSIZ2, OsOTS3, and OsELS2. Some AS forms have the potential to alter protein domains and catalytic centers. We also performed the molecular and phenotypic characterization of T-DNA insertion lines of some of the genes under study. Knockouts of OsFUG1 and OsELS1 showed increased SUMOylation levels and non-overlapping phenotypes. The fug1 line showed a dwarf phenotype, and significant defects in fertility, seed weight, and panicle architecture, while the els1 line showed early flowering and decreased plant height. We suggest that OsELS1 is an ortholog of AtEsd4, which was also supported by our phylogenetic analysis.

CONCLUSIONS: Overall, we provide a comprehensive analysis of the rice SUMOylation machinery and discuss possible effects of the regulation of these genes at the transcriptional and post-transcriptional level. We also contribute to the characterization of two rice SUMO proteases, OsELS1 and OsFUG1.}, } @article {pmid30541426, year = {2018}, author = {Li, Q and Noel-MacDonnell, JR and Koestler, DC and Goode, EL and Fridley, BL}, title = {Subject level clustering using a negative binomial model for small transcriptomic studies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {474}, doi = {10.1186/s12859-018-2556-9}, pmid = {30541426}, issn = {1471-2105}, support = {P30 CA168524/CA/NCI NIH HHS/United States ; P30 CA168524//National Cancer Institute/ ; }, mesh = {Cluster Analysis ; Female ; Humans ; Male ; *Models, Statistical ; *Normal Distribution ; Transcriptome/*immunology ; }, abstract = {BACKGROUND: Unsupervised clustering represents one of the most widely applied methods in analysis of high-throughput 'omics data. A variety of unsupervised model-based or parametric clustering methods and non-parametric clustering methods have been proposed for RNA-seq count data, most of which perform well for large samples, e.g. N ≥ 500. A common issue when analyzing limited samples of RNA-seq count data is that the data follows an over-dispersed distribution, and thus a Negative Binomial likelihood model is often used. Thus, we have developed a Negative Binomial model-based (NBMB) clustering approach for application to RNA-seq studies.

RESULTS: We have developed a Negative Binomial Model-Based (NBMB) method to cluster samples using a stochastic version of the expectation-maximization algorithm. A simulation study involving various scenarios was completed to compare the performance of NBMB to Gaussian model-based or Gaussian mixture modeling (GMM). NBMB was also applied for the clustering of two RNA-seq studies; type 2 diabetes study (N = 96) and TCGA study of ovarian cancer (N = 295). Simulation results showed that NBMB outperforms GMM applied with different transformations in majority of scenarios with limited sample size. Additionally, we found that NBMB outperformed GMM for small clusters distance regardless of sample size. Increasing total number of genes with fixed proportion of differentially expressed genes does not change the outperformance of NBMB, but improves the overall performance of GMM. Analysis of type 2 diabetes and ovarian cancer tumor data with NBMB found good agreement with the reported disease subtypes and the gene expression patterns. This method is available in an R package on CRAN named NB.MClust.

CONCLUSION: Use of Negative Binomial model based clustering is advisable when clustering over dispersed RNA-seq count data.}, } @article {pmid30541424, year = {2018}, author = {Chen, G and Ye, X and Zhang, S and Zhu, S and Yuan, L and Hou, J and Wang, C}, title = {Comparative Transcriptome Analysis between Fertile and CMS Flower Buds in Wucai (Brassica campestris L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {908}, doi = {10.1186/s12864-018-5331-4}, pmid = {30541424}, issn = {1471-2164}, support = {2017YFD0101803//National Key R & D Program of China/ ; 17030701013//Provincial Science and Technology Major Project of Anhui/ ; KJ2017ZD15//Major Projects of Natural Science Research Funds in Support of Colleges/ ; KJ2017A153//Key Projects of Natural Science Research Funds in Support of Colleges/ ; 31701910//National Natural Science Foundation of China/ ; 31801853//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Wucai (Brassica campestris L. ssp. chinensis var. rosularis Tsen) is a variant of nonheading Chinese cabbage (Brassica campestris L.), which is one of the major vegetables in China. Cytoplasmic male sterility (CMS) has been used for Wucai breeding in recent years. However, the underlying molecular mechanism of Wucai CMS remains unclear. In this study, the phenotypic and cytological features of Wucai CMS were observed by anatomical analysis, and a comparative transcriptome analysis was carried out to identify genes related to male sterility using Illumina RNA sequencing technology (RNA-Seq).

RESULTS: Microscopic observation demonstrated that tapetum development was abnormal in the CMS line, which failed to produce fertile pollen. Bioinformatics analysis detected 4430 differentially expressed genes (DEGs) between the fertile and sterile flower buds. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed to better understand the functions of these DEGs. Among the DEGs, 35 genes (53 DEGS) were implicated in anther and pollen development, and 11 genes were involved in pollen cell wall formation and modification; most of these showed downregulated expression in sterile buds. In addition, several genes related to tapetum development (A6, AMS, MS1, MYB39, and TSM1) and a few genes annotated to flowering (CO, AP3, VIN3, FLC, FT, and AGL) were detected and confirmed by qRT-PCR as being expressed at the meiosis, tetrad, and uninucleate microspore stages, thus implying possible roles in specifying or determining the fate and development of the tapetum, male gametophyte and stamen. Moreover, the top four largest transcription factor families (MYB, bHLH, NAC and WRKY) were analyzed, and most showed reduced expression in sterile buds. These differentially expressed transcription factors might result in abortion of pollen development in Wucai.

CONCLUSION: The present comparative transcriptome analysis suggested that many key genes and transcription factors involved in anther development show reduced gene expression patterns in the CMS line, which might contribute to male sterility in Wucai. This study provides valuable information for a better understanding of CMS molecular mechanisms and functional genome studies in Wucai.}, } @article {pmid30524730, year = {2018}, author = {Austad, SN and Hoffman, JM}, title = {Is antagonistic pleiotropy ubiquitous in aging biology?.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {287-294}, pmid = {30524730}, issn = {2050-6201}, abstract = {Lay Summary: An evolutionary mechanism of aging was hypothesized 60 years ago to be the genetic trade-off between early life fitness and late life mortality. Genetic evidence supporting this hypothesis was unavailable then, but has accumulated recently. These tradeoffs, known as antagonistic pleiotropy, are common, perhaps ubiquitous. George Williams' 1957 paper developed the antagonistic pleiotropy hypothesis of aging, which had previously been hinted at by Peter Medawar. Antagonistic pleiotropy, as it applies to aging, hypothesizes that animals possess genes that enhance fitness early in life but diminish it in later life and that such genes can be favored by natural selection because selection is stronger early in life even as they cause the aging phenotype to emerge. No genes of the sort hypothesized by Williams were known 60 years ago, but modern molecular biology has now discovered hundreds of genes that, when their activity is enhanced, suppressed, or turned off, lengthen life and enhance health under laboratory conditions. Does this provide strong support for Williams' hypothesis? What are the implications of Williams' hypothesis for the modern goal of medically intervening to enhance and prolong human health? Here we briefly review the current state of knowledge on antagonistic pleiotropy both under wild and laboratory conditions. Overall, whenever antagonistic pleiotropy effects have been seriously investigated, they have been found. However, not all trade-offs are directly between reproduction and longevity as is often assumed. The discovery that antagonistic pleiotropy is common if not ubiquitous implies that a number of molecular mechanisms of aging may be widely shared among organisms and that these mechanisms of aging can be potentially alleviated by targeted interventions.}, } @article {pmid30524133, year = {2018}, author = {Suryanarayanan, S and Kleinman, DL and Gratton, C and Toth, A and Guedot, C and Groves, R and Piechowski, J and Moore, B and Hagedorn, D and Kauth, D and Swan, H and Celley, M}, title = {Collaboration Matters: Honey Bee Health as a Transdisciplinary Model for Understanding Real-World Complexity.}, journal = {Bioscience}, volume = {68}, number = {12}, pages = {990-995}, pmid = {30524133}, issn = {0006-3568}, abstract = {We develop a transdisciplinary deliberative model that moves beyond traditional scientific collaborations to include nonscientists in designing complexity-oriented research. We use the case of declining honey bee health as an exemplar of complex real-world problems requiring cross-disciplinary intervention. Honey bees are important pollinators of the fruits and vegetables we eat. In recent years, these insects have been dying at alarming rates. To prompt the reorientation of research toward the complex reality in which bees face multiple challenges, we came together as a group, including beekeepers, farmers, and scientists. Over a 2-year period, we deliberated about how to study the problem of honey bee deaths and conducted field experiments with bee colonies. We show trust and authority to be crucial factors shaping such collaborative research, and we offer a model for structuring collaboration that brings scientists and nonscientists together with the key objects and places of their shared concerns across time.}, } @article {pmid30523662, year = {2018}, author = {Heads, M}, title = {Recent advances in New Caledonian biogeography.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12485}, pmid = {30523662}, issn = {1469-185X}, abstract = {The biota of New Caledonia is one of the most unusual in the world. It displays high diversity and endemism, many peculiar absences, and far-flung biogeographic affinities. For example, New Caledonia is the only place on Earth with both main clades of flowering plants - the endemic Amborella and 'all the rest', and it also has the highest concentration of diversity in conifers. The discovery of Amborella's phylogenetic position led to a surge of interest in New Caledonian biogeography, and new studies are appearing at a rapid rate. This paper reviews work on the topic (mainly molecular studies) published since 2013. One current debate is focused on whether any biota survived the marine transgressions of the Paleocene and Eocene. Total submersion would imply that the entire fauna was derived by long-distance dispersal from continental areas since the Eocene, but only if no other islands (now submerged) were emergent. A review of the literature suggests there is little actual evidence in geology for complete submersion. An alternative explanation for New Caledonia's diversity is that the archipelago acted as a refugium, and that the biota avoided the extinctions that occurred in Australia. However, this is contradicted by the many groups that are anomalously absent or depauperate in New Caledonia, although represented there by a sister group. The anomalous absences, together with the unusual levels of endemism, can both be explained by vicariance at breaks in and around New Caledonia. New Caledonia has always been situated at or near a plate boundary, and its complex geological history includes the addition of new terranes (by accretion), orogeny, and rifting. New Caledonia comprises 'basement' terranes that were part of Gondwana, as well as island arc and forearc terranes that accreted to the basement after it separated from Gondwana. The regional tectonic history helps explain the regional biogeography, as well as distribution patterns within New Caledonia. These include endemics on the basement terranes (for example, the basal angiosperm, Amborella), disjunctions at the West Caledonian fault zone, and great biotic differences between Grande Terre and the Loyalty Islands.}, } @article {pmid30523653, year = {2018}, author = {Pinharanda, A and Rousselle, M and Martin, SH and Hanly, JJ and Davey, JW and Kumar, S and Galtier, N and Jiggins, CD}, title = {Sexually dimorphic gene expression and transcriptome evolution provide mixed evidence for a fast-Z effect in Heliconius.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13410}, pmid = {30523653}, issn = {1420-9101}, abstract = {Sex chromosomes have different evolutionary properties compared to autosomes due to their hemizygous nature. In particular, recessive mutations are more readily exposed to selection, which can lead to faster rates of molecular evolution. Here, we report patterns of gene expression and molecular evolution for a group of butterflies. First, we improve the completeness of the Heliconius melpomene reference annotation, a neotropical butterfly with a ZW sex determination system. Then, we analyse RNA from male and female whole abdomens and sequence female ovary and gut tissue to identify sex- and tissue-specific gene expression profiles in H. melpomene. Using these expression profiles, we compare (a) sequence divergence and polymorphism; (b) the strength of positive and negative selection; and (c) rates of adaptive evolution, for Z and autosomal genes between two species of Heliconius butterflies, H. melpomene and H. erato. We show that the rate of adaptive substitutions is higher for Z than autosomal genes, but contrary to expectation, it is also higher for male-biased than female-biased genes. Additionally, we find no significant increase in the rate of adaptive evolution or purifying selection on genes expressed in ovary tissue, a heterogametic-specific tissue. Our results contribute to a growing body of literature from other ZW systems that also provide mixed evidence for a fast-Z effect where hemizygosity influences the rate of adaptive substitutions.}, } @article {pmid30523274, year = {2018}, author = {Freimer, NB and Mohr, DC}, title = {Integrating behavioural health tracking in human genetics research.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41576-018-0078-y}, pmid = {30523274}, issn = {1471-0064}, } @article {pmid30523118, year = {2018}, author = {Feng, Z and Zou, X and Chen, Y and Wang, H and Duan, Y and Bruick, RK}, title = {Modulation of HIF-2α PAS-B domain contributes to physiological responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13240-13245}, doi = {10.1073/pnas.1810897115}, pmid = {30523118}, issn = {1091-6490}, abstract = {Hypoxia-inducible factors (HIFs) are transcription factors in the basic helix-loop-helix PER-ARNT-SIM (bHLH-PAS) protein family that contain internal hydrophobic cavities within their PAS-A and PAS-B domains. Among HIFs, the HIF-2α PAS-B domain contains a relatively large cavity exploited for the development of specific artificial ligands such as PT2399. Administration of PT2399 could suppress HIF-2α target gene expression without affecting HIF-1 activity in mice under hypoxia conditions. A single mutation (S305M) within the HIF-2α PAS-B domain suppressed HIF-2α activity while conferring resistance to PT2399 in vivo, indicating the vital role of PAS-B domain in HIF-2α hypoxia response. In contrast, the mutant mice did not phenocopy PT2399 intervention in wild-type mice under metabolic stress. Under a high-fat diet (HFD), the mutant mice exert enhanced adipogenesis and obtain larger adipose mass and body weight gain compared to wild type. However, administration of PT2399 along with HFD feeding sufficiently suppressed HFD-induced body weight and adipose mass increase through suppression of adipogenesis and lipogenesis. The accompanying decreased lipid accumulation in the liver and improved glucose tolerance in wild-type mice were not observed in the mutant mice indicating negative regulation of HIF-2α on obesity and a complex role for the PAS-B domain in metabolic regulation. Notably, short-term administration of PT2399 to obese mice decreased adipose mass and improved metabolic condition. These results indicate a regulatory role for HIF-2α in obesity progression and suggest a therapeutic opportunity for PT2399 in obesity and associated metabolic disorders.}, } @article {pmid30523117, year = {2018}, author = {Akerlof, GA and Michaillat, P}, title = {Persistence of false paradigms in low-power sciences.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13228-13233}, doi = {10.1073/pnas.1816454115}, pmid = {30523117}, issn = {1091-6490}, abstract = {We develop a model describing how false paradigms may persist, hindering scientific progress. The model features two paradigms, one describing reality better than the other. Tenured scientists display homophily: They favor tenure candidates who adhere to their paradigm. As in statistics, power is the probability (absent any bias) of denying tenure to scientists adhering to the false paradigm. The model shows that because of homophily, when power is low, the false paradigm may prevail. Then, only an increase in power can ignite convergence to the true paradigm. Historical case studies suggest that low power comes either from lack of empirical evidence or from reluctance to base tenure decisions on available evidence.}, } @article {pmid30523113, year = {2018}, author = {Frater, PN and Sullivan, LL}, title = {A short guide to working remotely.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1206}, doi = {10.1126/science.362.6419.1206}, pmid = {30523113}, issn = {1095-9203}, } @article {pmid30523112, year = {2018}, author = {Harris, CJ and Scheibe, M and Wongpalee, SP and Liu, W and Cornett, EM and Vaughan, RM and Li, X and Chen, W and Xue, Y and Zhong, Z and Yen, L and Barshop, WD and Rayatpisheh, S and Gallego-Bartolome, J and Groth, M and Wang, Z and Wohlschlegel, JA and Du, J and Rothbart, SB and Butter, F and Jacobsen, SE}, title = {A DNA methylation reader complex that enhances gene transcription.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1182-1186}, doi = {10.1126/science.aar7854}, pmid = {30523112}, issn = {1095-9203}, support = {R37 GM060398/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 GM060398/GM/NIGMS NIH HHS/United States ; T32 GM007185/GM/NIGMS NIH HHS/United States ; R35 GM124736/GM/NIGMS NIH HHS/United States ; R01 GM089778/GM/NIGMS NIH HHS/United States ; }, abstract = {DNA methylation generally functions as a repressive transcriptional signal, but it is also known to activate gene expression. In either case, the downstream factors remain largely unknown. By using comparative interactomics, we isolated proteins in Arabidopsis thaliana that associate with methylated DNA. Two SU(VAR)3-9 homologs, the transcriptional antisilencing factor SUVH1, and SUVH3, were among the methyl reader candidates. SUVH1 and SUVH3 bound methylated DNA in vitro, were associated with euchromatic methylation in vivo, and formed a complex with two DNAJ domain-containing homologs, DNAJ1 and DNAJ2. Ectopic recruitment of DNAJ1 enhanced gene transcription in plants, yeast, and mammals. Thus, the SUVH proteins bind to methylated DNA and recruit the DNAJ proteins to enhance proximal gene expression, thereby counteracting the repressive effects of transposon insertion near genes.}, } @article {pmid30523111, year = {2018}, author = {Ackermann, S and Cartolano, M and Hero, B and Welte, A and Kahlert, Y and Roderwieser, A and Bartenhagen, C and Walter, E and Gecht, J and Kerschke, L and Volland, R and Menon, R and Heuckmann, JM and Gartlgruber, M and Hartlieb, S and Henrich, KO and Okonechnikov, K and Altmüller, J and Nürnberg, P and Lefever, S and de Wilde, B and Sand, F and Ikram, F and Rosswog, C and Fischer, J and Theissen, J and Hertwig, F and Singhi, AD and Simon, T and Vogel, W and Perner, S and Krug, B and Schmidt, M and Rahmann, S and Achter, V and Lang, U and Vokuhl, C and Ortmann, M and Büttner, R and Eggert, A and Speleman, F and O'Sullivan, RJ and Thomas, RK and Berthold, F and Vandesompele, J and Schramm, A and Westermann, F and Schulte, JH and Peifer, M and Fischer, M}, title = {A mechanistic classification of clinical phenotypes in neuroblastoma.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1165-1170}, doi = {10.1126/science.aat6768}, pmid = {30523111}, issn = {1095-9203}, abstract = {Neuroblastoma is a pediatric tumor of the sympathetic nervous system. Its clinical course ranges from spontaneous tumor regression to fatal progression. To investigate the molecular features of the divergent tumor subtypes, we performed genome sequencing on 416 pretreatment neuroblastomas and assessed telomere maintenance mechanisms in 208 of these tumors. We found that patients whose tumors lacked telomere maintenance mechanisms had an excellent prognosis, whereas the prognosis of patients whose tumors harbored telomere maintenance mechanisms was substantially worse. Survival rates were lowest for neuroblastoma patients whose tumors harbored telomere maintenance mechanisms in combination with RAS and/or p53 pathway mutations. Spontaneous tumor regression occurred both in the presence and absence of these mutations in patients with telomere maintenance-negative tumors. On the basis of these data, we propose a mechanistic classification of neuroblastoma that may benefit the clinical management of patients.}, } @article {pmid30523110, year = {2018}, author = {Stapels, DAC and Hill, PWS and Westermann, AJ and Fisher, RA and Thurston, TL and Saliba, AE and Blommestein, I and Vogel, J and Helaine, S}, title = {Salmonella persisters undermine host immune defenses during antibiotic treatment.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1156-1160}, doi = {10.1126/science.aat7148}, pmid = {30523110}, issn = {1095-9203}, support = {MR/M009629/1//Medical Research Council/United Kingdom ; //Medical Research Council/United Kingdom ; }, abstract = {Many bacterial infections are hard to treat and tend to relapse, possibly due to the presence of antibiotic-tolerant persisters. In vitro, persister cells appear to be dormant. After uptake of Salmonella species by macrophages, nongrowing persisters also occur, but their physiological state is poorly understood. In this work, we show that Salmonella persisters arising during macrophage infection maintain a metabolically active state. Persisters reprogram macrophages by means of effectors secreted by the Salmonella pathogenicity island 2 type 3 secretion system. These effectors dampened proinflammatory innate immune responses and induced anti-inflammatory macrophage polarization. Such reprogramming allowed nongrowing Salmonella cells to survive for extended periods in their host. Persisters undermining host immune defenses might confer an advantage to the pathogen during relapse once antibiotic pressure is relieved.}, } @article {pmid30523109, year = {2018}, author = {Sunku, SS and Ni, GX and Jiang, BY and Yoo, H and Sternbach, A and McLeod, AS and Stauber, T and Xiong, L and Taniguchi, T and Watanabe, K and Kim, P and Fogler, MM and Basov, DN}, title = {Photonic crystals for nano-light in moiré graphene superlattices.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1153-1156}, doi = {10.1126/science.aau5144}, pmid = {30523109}, issn = {1095-9203}, abstract = {Graphene is an atomically thin plasmonic medium that supports highly confined plasmon polaritons, or nano-light, with very low loss. Electronic properties of graphene can be drastically altered when it is laid upon another graphene layer, resulting in a moiré superlattice. The relative twist angle between the two layers is a key tuning parameter of the interlayer coupling in thus-obtained twisted bilayer graphene (TBG). We studied the propagation of plasmon polaritons in TBG by infrared nano-imaging. We discovered that the atomic reconstruction occurring at small twist angles transforms the TBG into a natural plasmon photonic crystal for propagating nano-light. This discovery points to a pathway for controlling nano-light by exploiting quantum properties of graphene and other atomically layered van der Waals materials, eliminating the need for arduous top-down nanofabrication.}, } @article {pmid30523108, year = {2018}, author = {Li, J and Zhang, RX and Yin, Z and Zhang, J and Watanabe, K and Taniguchi, T and Liu, C and Zhu, J}, title = {A valley valve and electron beam splitter.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1149-1152}, doi = {10.1126/science.aao5989}, pmid = {30523108}, issn = {1095-9203}, abstract = {Developing alternative paradigms of electronics beyond silicon technology requires the exploration of fundamentally new physical mechanisms, such as the valley-specific phenomena in hexagonal two-dimensional materials. We realize ballistic valley Hall kink states in bilayer graphene and demonstrate gate-controlled current transmission in a four-kink router device. The operations of a waveguide, a valve, and a tunable electron beam splitter are demonstrated. The valley valve exploits the valley-momentum locking of the kink states and reaches an on/off ratio of 8 at zero magnetic field. A magnetic field enables a full-range tunable coherent beam splitter. These results pave a path to building a scalable, coherent quantum transportation network based on the kink states.}, } @article {pmid30523107, year = {2018}, author = {Davis, VK and Bates, CM and Omichi, K and Savoie, BM and Momčilović, N and Xu, Q and Wolf, WJ and Webb, MA and Billings, KJ and Chou, NH and Alayoglu, S and McKenney, RK and Darolles, IM and Nair, NG and Hightower, A and Rosenberg, D and Ahmed, M and Brooks, CJ and Miller, TF and Grubbs, RH and Jones, SC}, title = {Room-temperature cycling of metal fluoride electrodes: Liquid electrolytes for high-energy fluoride ion cells.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1144-1148}, doi = {10.1126/science.aat7070}, pmid = {30523107}, issn = {1095-9203}, abstract = {Fluoride ion batteries are potential "next-generation" electrochemical storage devices that offer high energy density. At present, such batteries are limited to operation at high temperatures because suitable fluoride ion-conducting electrolytes are known only in the solid state. We report a liquid fluoride ion-conducting electrolyte with high ionic conductivity, wide operating voltage, and robust chemical stability based on dry tetraalkylammonium fluoride salts in ether solvents. Pairing this liquid electrolyte with a copper-lanthanum trifluoride (Cu@LaF3) core-shell cathode, we demonstrate reversible fluorination and defluorination reactions in a fluoride ion electrochemical cell cycled at room temperature. Fluoride ion-mediated electrochemistry offers a pathway toward developing capacities beyond that of lithium ion technology.}, } @article {pmid30523106, year = {2018}, author = {Silver, D and Hubert, T and Schrittwieser, J and Antonoglou, I and Lai, M and Guez, A and Lanctot, M and Sifre, L and Kumaran, D and Graepel, T and Lillicrap, T and Simonyan, K and Hassabis, D}, title = {A general reinforcement learning algorithm that masters chess, shogi, and Go through self-play.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1140-1144}, doi = {10.1126/science.aar6404}, pmid = {30523106}, issn = {1095-9203}, abstract = {The game of chess is the longest-studied domain in the history of artificial intelligence. The strongest programs are based on a combination of sophisticated search techniques, domain-specific adaptations, and handcrafted evaluation functions that have been refined by human experts over several decades. By contrast, the AlphaGo Zero program recently achieved superhuman performance in the game of Go by reinforcement learning from self-play. In this paper, we generalize this approach into a single AlphaZero algorithm that can achieve superhuman performance in many challenging games. Starting from random play and given no domain knowledge except the game rules, AlphaZero convincingly defeated a world champion program in the games of chess and shogi (Japanese chess), as well as Go.}, } @article {pmid30523105, year = {2018}, author = {Chen, J and Zhu, E and Liu, J and Zhang, S and Lin, Z and Duan, X and Heinz, H and Huang, Y and De Yoreo, JJ}, title = {Building two-dimensional materials one row at a time: Avoiding the nucleation barrier.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1135-1139}, doi = {10.1126/science.aau4146}, pmid = {30523105}, issn = {1095-9203}, abstract = {Assembly of two-dimensional (2D) molecular arrays on surfaces produces a wide range of architectural motifs exhibiting unique properties, but little attention has been given to the mechanism by which they nucleate. Using peptides selected for their binding affinity to molybdenum disulfide, we investigated nucleation of 2D arrays by molecularly resolved in situ atomic force microscopy and compared our results to molecular dynamics simulations. The arrays assembled one row at a time, and the nuclei were ordered from the earliest stages and formed without a free energy barrier or a critical size. The results verify long-standing but unproven predictions of classical nucleation theory in one dimension while revealing key interactions underlying 2D assembly.}, } @article {pmid30523104, year = {2018}, author = {Gumyusenge, A and Tran, DT and Luo, X and Pitch, GM and Zhao, Y and Jenkins, KA and Dunn, TJ and Ayzner, AL and Savoie, BM and Mei, J}, title = {Semiconducting polymer blends that exhibit stable charge transport at high temperatures.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1131-1134}, doi = {10.1126/science.aau0759}, pmid = {30523104}, issn = {1095-9203}, abstract = {Although high-temperature operation (i.e., beyond 150°C) is of great interest for many electronics applications, achieving stable carrier mobilities for organic semiconductors at elevated temperatures is fundamentally challenging. We report a general strategy to make thermally stable high-temperature semiconducting polymer blends, composed of interpenetrating semicrystalline conjugated polymers and high glass-transition temperature insulating matrices. When properly engineered, such polymer blends display a temperature-insensitive charge transport behavior with hole mobility exceeding 2.0 cm2/V·s across a wide temperature range from room temperature up to 220°C in thin-film transistors.}, } @article {pmid30523103, year = {2018}, author = {Halperin, JL}, title = {No conflict of interest in data monitoring.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1123}, doi = {10.1126/science.aau9738}, pmid = {30523103}, issn = {1095-9203}, } @article {pmid30523102, year = {2018}, author = {Deutsch, CA and Tewksbury, JJ and Merrill, SC and Huey, RB and Battisti, DS and Naylor, RL}, title = {Model vs. experiment to predict crop losses-Response.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1122-1123}, doi = {10.1126/science.aav7405}, pmid = {30523102}, issn = {1095-9203}, mesh = {*Agriculture ; *Crops, Agricultural ; }, } @article {pmid30523101, year = {2018}, author = {Parmesan, C and Hanley, ME and Singer, MC}, title = {Model vs. experiment to predict crop losses.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1122}, doi = {10.1126/science.aav4827}, pmid = {30523101}, issn = {1095-9203}, mesh = {Animals ; *Climate ; *Insecta ; }, } @article {pmid30523100, year = {2018}, author = {Bento, AM and Gillingham, K and Jacobsen, MR and Knittel, CR and Leard, B and Linn, J and McConnell, V and Rapson, D and Sallee, JM and van Benthem, AA and Whitefoot, KS}, title = {Flawed analyses of U.S. auto fuel economy standards.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1119-1121}, doi = {10.1126/science.aav1458}, pmid = {30523100}, issn = {1095-9203}, } @article {pmid30523099, year = {2018}, author = {Campbell, M}, title = {Mastering board games.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1118}, doi = {10.1126/science.aav1175}, pmid = {30523099}, issn = {1095-9203}, } @article {pmid30523098, year = {2018}, author = {Gomez-Salinero, JM and Rafii, S}, title = {Endothelial cell adaptation in regeneration.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1116-1117}, doi = {10.1126/science.aar4800}, pmid = {30523098}, issn = {1095-9203}, } @article {pmid30523097, year = {2018}, author = {Schon, EA}, title = {Bioenergetics through thick and thin.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1114-1115}, doi = {10.1126/science.aav7629}, pmid = {30523097}, issn = {1095-9203}, mesh = {*Cell Respiration ; *Energy Metabolism ; Membrane Lipids ; }, } @article {pmid30523096, year = {2018}, author = {Kump, L}, title = {Climate change and marine mass extinction.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1113-1114}, doi = {10.1126/science.aav736}, pmid = {30523096}, issn = {1095-9203}, mesh = {*Climate Change ; *Extinction, Biological ; }, } @article {pmid30523095, year = {2018}, author = {Phillips, MA and Goldberg, DE}, title = {Toward a chemical vaccine for malaria.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1112-1113}, doi = {10.1126/science.aav7479}, pmid = {30523095}, issn = {1095-9203}, } @article {pmid30523094, year = {2018}, author = {Kahr, B and Ward, MD}, title = {Barrier(less) islands.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1111}, doi = {10.1126/science.aav7009}, pmid = {30523094}, issn = {1095-9203}, mesh = {Islands ; }, } @article {pmid30523093, year = {2018}, author = {Piller, C}, title = {At arm's length.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1100-1103}, doi = {10.1126/science.362.6419.1100}, pmid = {30523093}, issn = {1095-9203}, } @article {pmid30523092, year = {2018}, author = {Wadman, M}, title = {Taking aim.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1096-1099}, doi = {10.1126/science.362.6419.1096}, pmid = {30523092}, issn = {1095-9203}, } @article {pmid30523091, year = {2018}, author = {Vogel, G}, title = {Demotion dismays researchers at storied Danish museum.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1095}, doi = {10.1126/science.362.6419.1095}, pmid = {30523091}, issn = {1095-9203}, } @article {pmid30523090, year = {2018}, author = {Cohen, J}, title = {Universal flu vaccine is 'an alchemist's dream'.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1094}, doi = {10.1126/science.362.6419.1094}, pmid = {30523090}, issn = {1095-9203}, } @article {pmid30523089, year = {2018}, author = {Stokstad, E}, title = {Uncertainty boosts Brexit jitters for U.K. scientists.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1092-1093}, doi = {10.1126/science.362.6419.1092}, pmid = {30523089}, issn = {1095-9203}, } @article {pmid30523088, year = {2018}, author = {Normile, D}, title = {For China, a CRISPR first goes too far.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1091}, doi = {10.1126/science.362.6419.1091}, pmid = {30523088}, issn = {1095-9203}, } @article {pmid30523087, year = {2018}, author = {Cohen, J}, title = {What now for human genome editing?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1090-1092}, doi = {10.1126/science.362.6419.1090}, pmid = {30523087}, issn = {1095-9203}, } @article {pmid30523086, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1088-1089}, doi = {10.1126/science.362.6419.1088}, pmid = {30523086}, issn = {1095-9203}, } @article {pmid30523085, year = {2018}, author = {Kasparov, G}, title = {Chess, a Drosophila of reasoning.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1087}, doi = {10.1126/science.aaw2221}, pmid = {30523085}, issn = {1095-9203}, } @article {pmid30523084, year = {2018}, author = {Antonova-Koch, Y and Meister, S and Abraham, M and Luth, MR and Ottilie, S and Lukens, AK and Sakata-Kato, T and Vanaerschot, M and Owen, E and Jado, JC and Maher, SP and Calla, J and Plouffe, D and Zhong, Y and Chen, K and Chaumeau, V and Conway, AJ and McNamara, CW and Ibanez, M and Gagaring, K and Serrano, FN and Eribez, K and Taggard, CM and Cheung, AL and Lincoln, C and Ambachew, B and Rouillier, M and Siegel, D and Nosten, F and Kyle, DE and Gamo, FJ and Zhou, Y and Llinás, M and Fidock, DA and Wirth, DF and Burrows, J and Campo, B and Winzeler, EA}, title = {Open-source discovery of chemical leads for next-generation chemoprotective antimalarials.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {}, doi = {10.1126/science.aat9446}, pmid = {30523084}, issn = {1095-9203}, support = {R01 AI103058/AI/NIAID NIH HHS/United States ; R01 AI090141/AI/NIAID NIH HHS/United States ; P50 GM085764/GM/NIGMS NIH HHS/United States ; R01 AI093716/AI/NIAID NIH HHS/United States ; }, abstract = {To discover leads for next-generation chemoprotective antimalarial drugs, we tested more than 500,000 compounds for their ability to inhibit liver-stage development of luciferase-expressing Plasmodium spp. parasites (681 compounds showed a half-maximal inhibitory concentration of less than 1 micromolar). Cluster analysis identified potent and previously unreported scaffold families as well as other series previously associated with chemoprophylaxis. Further testing through multiple phenotypic assays that predict stage-specific and multispecies antimalarial activity distinguished compound classes that are likely to provide symptomatic relief by reducing asexual blood-stage parasitemia from those which are likely to only prevent malaria. Target identification by using functional assays, in vitro evolution, or metabolic profiling revealed 58 mitochondrial inhibitors but also many chemotypes possibly with previously unidentified mechanisms of action.}, } @article {pmid30523083, year = {2018}, author = {Schmitz, OJ and Wilmers, CC and Leroux, SJ and Doughty, CE and Atwood, TB and Galetti, M and Davies, AB and Goetz, SJ}, title = {Animals and the zoogeochemistry of the carbon cycle.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {}, doi = {10.1126/science.aar3213}, pmid = {30523083}, issn = {1095-9203}, abstract = {Predicting and managing the global carbon cycle requires scientific understanding of ecosystem processes that control carbon uptake and storage. It is generally assumed that carbon cycling is sufficiently characterized in terms of uptake and exchange between ecosystem plant and soil pools and the atmosphere. We show that animals also play an important role by mediating carbon exchange between ecosystems and the atmosphere, at times turning ecosystem carbon sources into sinks, or vice versa. Animals also move across landscapes, creating a dynamism that shapes landscape-scale variation in carbon exchange and storage. Predicting and measuring carbon cycling under such dynamism is an important scientific challenge. We explain how to link analyses of spatial ecosystem functioning, animal movement, and remote sensing of animal habitats with carbon dynamics across landscapes.}, } @article {pmid30523082, year = {2018}, author = {Penn, JL and Deutsch, C and Payne, JL and Sperling, EA}, title = {Temperature-dependent hypoxia explains biogeography and severity of end-Permian marine mass extinction.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {}, doi = {10.1126/science.aat1327}, pmid = {30523082}, issn = {1095-9203}, abstract = {Rapid climate change at the end of the Permian Period (~252 million years ago) is the hypothesized trigger for the largest mass extinction in Earth's history. We present model simulations of the Permian/Triassic climate transition that reproduce the ocean warming and oxygen (O2) loss indicated by the geologic record. The effect of these changes on animal survival is evaluated using the Metabolic Index (Φ), a measure of scope for aerobic activity governed by organismal traits sampled in diverse modern species. Modeled loss of aerobic habitat predicts lower extinction intensity in the tropics, a pattern confirmed with a spatially explicit analysis of the marine fossil record. The combined physiological stresses of ocean warming and O2 loss can account for more than half the magnitude of the "Great Dying."}, } @article {pmid30523081, year = {2018}, author = {Nortmann, L and Pallé, E and Salz, M and Sanz-Forcada, J and Nagel, E and Alonso-Floriano, FJ and Czesla, S and Yan, F and Chen, G and Snellen, IAG and Zechmeister, M and Schmitt, JHMM and López-Puertas, M and Casasayas-Barris, N and Bauer, FF and Amado, PJ and Caballero, JA and Dreizler, S and Henning, T and Lampón, M and Montes, D and Molaverdikhani, K and Quirrenbach, A and Reiners, A and Ribas, I and Sánchez-López, A and Schneider, PC and Zapatero Osorio, MR}, title = {Ground-based detection of an extended helium atmosphere in the Saturn-mass exoplanet WASP-69b.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1388-1391}, doi = {10.1126/science.aat5348}, pmid = {30523081}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Hot gas giant exoplanets can lose part of their atmosphere due to strong stellar irradiation, and these losses can affect their physical and chemical evolution. Studies of atmospheric escape from exoplanets have mostly relied on space-based observations of the hydrogen Lyman-α line in the far ultraviolet region, which is strongly affected by interstellar absorption. Using ground-based high-resolution spectroscopy, we detected excess absorption in the helium triplet at 1083 nanometers during the transit of the Saturn-mass exoplanet WASP-69b, at a signal-to-noise ratio of 18. We measured line blueshifts of several kilometers per second and posttransit absorption, which we interpret as the escape of part of the atmosphere trailing behind the planet in comet-like form.}, } @article {pmid30523080, year = {2018}, author = {Allart, R and Bourrier, V and Lovis, C and Ehrenreich, D and Spake, JJ and Wyttenbach, A and Pino, L and Pepe, F and Sing, DK and Lecavelier des Etangs, A}, title = {Spectrally resolved helium absorption from the extended atmosphere of a warm Neptune-mass exoplanet.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1384-1387}, doi = {10.1126/science.aat5879}, pmid = {30523080}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Stellar heating causes atmospheres of close-in exoplanets to expand and escape. These extended atmospheres are difficult to observe because their main spectral signature-neutral hydrogen at ultraviolet wavelengths-is strongly absorbed by interstellar medium. We report the detection of the near-infrared triplet of neutral helium in the transiting warm Neptune-mass exoplanet HAT-P-11b by using ground-based, high-resolution observations. The helium feature is repeatable over two independent transits, with an average absorption depth of 1.08 ± 0.05%. Interpreting absorption spectra with three-dimensional simulations of the planet's upper atmosphere suggests that it extends beyond 5 planetary radii, with a large-scale height and a helium mass loss rate of ≲3 × 105 grams per second. A net blue-shift of the absorption might be explained by high-altitude winds flowing at 3 kilometers per second from day to night-side.}, } @article {pmid30523079, year = {2019}, author = {Nichols, MA and Cheuk, LW and Okan, M and Hartke, TR and Mendez, E and Senthil, T and Khatami, E and Zhang, H and Zwierlein, MW}, title = {Spin transport in a Mott insulator of ultracold fermions.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6425}, pages = {383-387}, doi = {10.1126/science.aat4387}, pmid = {30523079}, issn = {1095-9203}, abstract = {Strongly correlated materials are expected to feature unconventional transport properties, such that charge, spin, and heat conduction are potentially independent probes of the dynamics. In contrast to charge transport, the measurement of spin transport in such materials is highly challenging. We observed spin conduction and diffusion in a system of ultracold fermionic atoms that realizes the half-filled Fermi-Hubbard model. For strong interactions, spin diffusion is driven by super-exchange and doublon-hole-assisted tunneling, and strongly violates the quantum limit of charge diffusion. The technique developed in this work can be extended to finite doping, which can shed light on the complex interplay between spin and charge in the Hubbard model.}, } @article {pmid30523078, year = {2019}, author = {Brown, PT and Mitra, D and Guardado-Sanchez, E and Nourafkan, R and Reymbaut, A and Hébert, CD and Bergeron, S and Tremblay, AS and Kokalj, J and Huse, DA and Schauß, P and Bakr, WS}, title = {Bad metallic transport in a cold atom Fermi-Hubbard system.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6425}, pages = {379-382}, doi = {10.1126/science.aat4134}, pmid = {30523078}, issn = {1095-9203}, abstract = {Strong interactions in many-body quantum systems complicate the interpretation of charge transport in such materials. To shed light on this problem, we study transport in a clean quantum system: ultracold lithium-6 in a two-dimensional optical lattice, a testing ground for strong interaction physics in the Fermi-Hubbard model. We determine the diffusion constant by measuring the relaxation of an imposed density modulation and modeling its decay hydrodynamically. The diffusion constant is converted to a resistivity by using the Nernst-Einstein relation. That resistivity exhibits a linear temperature dependence and shows no evidence of saturation, two characteristic signatures of a bad metal. The techniques we developed in this study may be applied to measurements of other transport quantities, including the optical conductivity and thermopower.}, } @article {pmid30523077, year = {2019}, author = {Yan, WX and Hunnewell, P and Alfonse, LE and Carte, JM and Keston-Smith, E and Sothiselvam, S and Garrity, AJ and Chong, S and Makarova, KS and Koonin, EV and Cheng, DR and Scott, DA}, title = {Functionally diverse type V CRISPR-Cas systems.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6422}, pages = {88-91}, doi = {10.1126/science.aav7271}, pmid = {30523077}, issn = {1095-9203}, abstract = {Type V CRISPR-Cas systems are distinguished by a single RNA-guided RuvC domain-containing effector, Cas12. Although effectors of subtypes V-A (Cas12a) and V-B (Cas12b) have been studied in detail, the distinct domain architectures and diverged RuvC sequences of uncharacterized Cas12 proteins suggest unexplored functional diversity. Here, we identify and characterize Cas12c, -g, -h, and -i. Cas12c, -h, and -i demonstrate RNA-guided double-stranded DNA (dsDNA) interference activity. Cas12i exhibits markedly different efficiencies of CRISPR RNA spacer complementary and noncomplementary strand cleavage resulting in predominant dsDNA nicking. Cas12g is an RNA-guided ribonuclease (RNase) with collateral RNase and single-strand DNase activities. Our study reveals the functional diversity emerging along different routes of type V CRISPR-Cas evolution and expands the CRISPR toolbox.}, } @article {pmid30523076, year = {2019}, author = {Harrison, OJ and Linehan, JL and Shih, HY and Bouladoux, N and Han, SJ and Smelkinson, M and Sen, SK and Byrd, AL and Enamorado, M and Yao, C and Tamoutounour, S and Van Laethem, F and Hurabielle, C and Collins, N and Paun, A and Salcedo, R and O'Shea, JJ and Belkaid, Y}, title = {Commensal-specific T cell plasticity promotes rapid tissue adaptation to injury.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6422}, pages = {}, doi = {10.1126/science.aat6280}, pmid = {30523076}, issn = {1095-9203}, abstract = {Barrier tissues are primary targets of environmental stressors and are home to the largest number of antigen-experienced lymphocytes in the body, including commensal-specific T cells. We found that skin-resident commensal-specific T cells harbor a paradoxical program characterized by a type 17 program associated with a poised type 2 state. Thus, in the context of injury and exposure to inflammatory mediators such as interleukin-18, these cells rapidly release type 2 cytokines, thereby acquiring contextual functions. Such acquisition of a type 2 effector program promotes tissue repair. Aberrant type 2 responses can also be unleashed in the context of local defects in immunoregulation. Thus, commensal-specific T cells co-opt tissue residency and cell-intrinsic flexibility as a means to promote both local immunity and tissue adaptation to injury.}, } @article {pmid30522530, year = {2018}, author = {Edlund, A and Yang, Y and Yooseph, S and He, X and Shi, W and McLean, JS}, title = {Uncovering complex microbiome activities via metatranscriptomics during 24 hours of oral biofilm assembly and maturation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {217}, pmid = {30522530}, issn = {2049-2618}, support = {R00DE024543//National Institute of Dental and Craniofacial Research/ ; K99DE024543//National Institute of Dental and Craniofacial Research/ ; 1R01DE023810//National Institute of Dental and Craniofacial Research/ ; 1R01DE023810//National Institute of Dental and Craniofacial Research/ ; 1R01DE023810//National Institute of Dental and Craniofacial Research/ ; 1R01DE020102//National Institute of Dental and Craniofacial Research/ ; 1R01DE020102//National Institute of Dental and Craniofacial Research/ ; 1R01DE020102//National Institute of Dental and Craniofacial Research/ ; 1R01DE026186//National Institute of Dental and Craniofacial Research/ ; 1R01DE026186//National Institute of Dental and Craniofacial Research/ ; 1R01DE026186//National Institute of Dental and Craniofacial Research/ ; R01GM095373//National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: Dental plaque is composed of hundreds of bacterial taxonomic units and represents one of the most diverse and stable microbial ecosystems associated with the human body. Taxonomic composition and functional capacity of mature plaque is gradually shaped during several stages of community assembly via processes such as co-aggregation, competition for space and resources, and by bacterially produced reactive agents. Knowledge on the dynamics of assembly within complex communities is very limited and derives mainly from studies composed of a limited number of bacterial species. To fill current knowledge gaps, we applied parallel metagenomic and metatranscriptomic analyses during assembly and maturation of an in vitro oral biofilm. This model system has previously demonstrated remarkable reproducibility in taxonomic composition across replicate samples during maturation.

RESULTS: Time course analysis of the biofilm maturation was performed by parallel sampling every 2-3 h for 24 h for both DNA and RNA. Metagenomic analyses revealed that community taxonomy changed most dramatically between three and six hours of growth when pH dropped from 6.5 to 5.5. By applying comparative metatranscriptome analysis we could identify major shifts in overall community activities between six and nine hours of growth when pH dropped below 5.5, as 29,015 genes were significantly up- or down- expressed. Several of the differentially expressed genes showed unique activities for individual bacterial genomes and were associated with pyruvate and lactate metabolism, two-component signaling pathways, production of antibacterial molecules, iron sequestration, pH neutralization, protein hydrolysis, and surface attachment. Our analysis also revealed several mechanisms responsible for the niche expansion of the cariogenic pathogen Lactobacillus fermentum.

CONCLUSION: It is highly regarded that acidic conditions in dental plaque cause a net loss of enamel from teeth. Here, as pH drops below 5.5 pH to 4.7, we observe blooms of cariogenic lactobacilli, and a transition point of many bacterial gene expression activities within the community. To our knowledge, this represents the first study of the assembly and maturation of a complex oral bacterial biofilm community that addresses gene level functional responses over time.}, } @article {pmid30522523, year = {2018}, author = {Willis, JR and González-Torres, P and Pittis, AA and Bejarano, LA and Cozzuto, L and Andreu-Somavilla, N and Alloza-Trabado, M and Valentín, A and Ksiezopolska, E and Company, C and Onywera, H and Montfort, M and Hermoso, A and Iraola-Guzmán, S and Saus, E and Labeeuw, A and Carolis, C and Hecht, J and Ponomarenko, J and Gabaldón, T}, title = {Citizen science charts two major "stomatotypes" in the oral microbiome of adolescents and reveals links with habits and drinking water composition.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {218}, pmid = {30522523}, issn = {2049-2618}, support = {BFU2015-67107//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; SEV-2012-02-08//Ministerio de Economía, Industria y Competitividad, Gobierno de España/ ; Saca la Lengua//"la Caixa" Foundation/ ; }, abstract = {BACKGROUND: The oral cavity comprises a rich and diverse microbiome, which plays important roles in health and disease. Previous studies have mostly focused on adult populations or in very young children, whereas the adolescent oral microbiome remains poorly studied. Here, we used a citizen science approach and 16S profiling to assess the oral microbiome of 1500 adolescents around Spain and its relationships with lifestyle, diet, hygiene, and socioeconomic and environmental parameters.

RESULTS: Our results provide a detailed snapshot of the adolescent oral microbiome and how it varies with lifestyle and other factors. In addition to hygiene and dietary habits, we found that the composition of tap water was related to important changes in the abundance of several bacterial genera. This points to an important role of drinking water in shaping the oral microbiota, which has been so far poorly explored. Overall, the microbiome samples of our study can be clustered into two broad compositional patterns (stomatotypes), driven mostly by Neisseria and Prevotella, respectively. These patterns show striking similarities with those found in unrelated populations.

CONCLUSIONS: We hypothesize that these stomatotypes represent two possible global optimal equilibria in the oral microbiome that reflect underlying constraints of the human oral niche. As such, they should be found across a variety of geographical regions, lifestyles, and ages.}, } @article {pmid30522518, year = {2018}, author = {Yismaw, AE and Tarekegn, AA}, title = {Proportion and factors of death among preterm neonates admitted in University of Gondar comprehensive specialized hospital neonatal intensive care unit, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {867}, pmid = {30522518}, issn = {1756-0500}, abstract = {OBJECTIVE: Neonatal mortality accounts for 43% of under-five child mortality in Ethiopia where preterm is the second leading cause of neonatal death and steadily increased in low-income countries. Therefore, assessing the proportion of death and associated factors among preterm neonates has a paramount importance in designing an effective strategy to intervene and achieve sustainable development goal.

RESULTS: In this study proportion of preterm neonatal death in this study was 28.8% [95% CI (25.1, 32.9)]. Complications during index pregnancy [AOR = 1.92, 95% CI (1.09, 3.38)], gestational age [AOR = 0.78, 95% CI (0.69, 0.91)], small for gestational age [AOR = 2.42, 95% CI (1.33, 4.38)], APGAR score at birth < 7 [AOR = 2.39, 95% CI (1.34, 4.27)], hyaline membrane disease [AOR = 5.15, 95% CI (2.83, 9.36)], neonatal respiratory distress at admission [AOR = 1.93, 95% CI (1.13, 3.31)], presence of jaundice [AOR = (3.39, 95% CI (1.90, 6.05)], received kangaroo mother care [AOR = 0.13, 95% CI (0.05, 0.35)], and hypoglycemia at admission [AOR = 3.86, 95% CI (2.12, 7.06)] were statistically significant. The proportion of preterm neonatal death was high. Ministry of health and responsible organizations should give special attention for preterm neonates to prevent life-threatening complications.}, } @article {pmid30522517, year = {2018}, author = {Kabalo, MY}, title = {Manifolds boosting severe acute malnutrition burden among children in and around Wolaita Zone, Southern Ethiopia: mini-review.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {870}, pmid = {30522517}, issn = {1756-0500}, abstract = {OBJECTIVES: Severe acute malnutrition (SAM) has been considered as the complex nutritional problem within developing countries. Alleviating its occurrence also exists in an anxiety. A series of studies were conducted to disclose evidences and documented by here author. Moreover key messages were abstracted with this review easing access of texts.

RESULTS: Due to pitiable sanitary practices 30% of cow milk had massive bacterial isolates like Escherichia coli; while usage of raw milk has been common do. Besides the mean severe household food insecurity was 6.5% and practice of family planning was 30%; whilst family size subsists as predictor for household food insecurity. The habits of exclusive breastfeeding, timely initiation of complementary feeding and apt complementary feeding were 78%, 34% and 11%, respectively with awareness as predictor. On the other hand SAM has been recognized as problem in children and treated mainly in outpatient therapeutic program by curative foods. Yet the provided foods were shared due to severe household food insecurity causing SAM recovery rate intolerable. So children get severely underfed by multidimensional determinants and need multifaceted strategies starting from awareness creation and alleviating household food insecurity.}, } @article {pmid30522503, year = {2018}, author = {Raab, M and Strebhardt, K and Rudd, CE}, title = {Immune adaptor protein SKAP1 (SKAP-55) forms homodimers as mediated by the N-terminal region.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {869}, pmid = {30522503}, issn = {1756-0500}, support = {092627/Z/10/Z//Wellcome Trust/United Kingdom ; 01GS0850//BMBF/ ; }, abstract = {OBJECTIVE: Immune cell adaptor protein SKAP1 couples the antigen-receptor (TCR/CD3) with the activation of LFA-1 adhesion in T-cells. Previous work by ourselves and others have shown that SKAP1 can directly bind to other adaptors such as ADAP and RapL. However, it has been unclear whether SKAP1 can form homodimers with itself and the regions within SKAP1 that mediated homodimer formation.

RESULTS: Here, we show that SKAP1 and SKAP2 form homodimers in cells. Homodimer formation of immune adaptor protein SKAP1 (SKAP-55) are mediated by residues A17 to L21 in the SKAP1 N-terminal region. SKAP1 dimer formation was not needed for its binding to RapL. These data indicate that the pathway linking SKAP1 to RapL is not dependent on the homo-dimerization of SKAP1.}, } @article {pmid30522499, year = {2018}, author = {Njim, T and Mbolingong, FN}, title = {Intimate partner violence and depression among pregnant women in the North west region of Cameroon: a research proposal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {868}, pmid = {30522499}, issn = {1756-0500}, abstract = {OBJECTIVES: Intimate partner violence (IPV) in pregnancy is a major public health concern due to its harmful effects on both the mother and the unborn foetus. In this study, we aim to assess the prevalence and correlates of both IPV and depression in pregnant women in the northwest region of Cameroon. Specifically: (1) To determine the prevalence of IPV in a group of pregnant women in the northwest region of Cameroon. (2) To determine the prevalence of depression amongst these women. (3) To assess the various sociodemographic determinants of IPV in these women. (4) To determine if IPV is associated with depression and to assess other sociodemographic and clinical correlates of depression.

RESULTS: This cross-sectional study will include a minimum of 369 pregnant women recruited by convenience sampling from primary and secondary healthcare facilities in the northwest region of the country. Data be collected via a printed questionnaire administered by a trained healthcare professional. IPV will be assessed using the World Health Organisation Violence Against Women Instrument and depression will be assessed using the Patient Health Questionnaire-9. Multivariable logistic regression will be used to identify independent predictors of IPV and depression.}, } @article {pmid30522480, year = {2018}, author = {Tian, Y and Gao, S and von der Heyde, EL and Hallmann, A and Nagel, G}, title = {Two-component cyclase opsins of green algae are ATP-dependent and light-inhibited guanylyl cyclases.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {144}, pmid = {30522480}, issn = {1741-7007}, abstract = {BACKGROUND: The green algae Chlamydomonas reinhardtii and Volvox carteri are important models for studying light perception and response, expressing many different photoreceptors. More than 10 opsins were reported in C. reinhardtii, yet only two-the channelrhodopsins-were functionally characterized. Characterization of new opsins would help to understand the green algae photobiology and to develop new tools for optogenetics.

RESULTS: Here we report the characterization of a novel opsin family from these green algae: light-inhibited guanylyl cyclases regulated through a two-component-like phosphoryl transfer, called "two-component cyclase opsins" (2c-Cyclops). We prove the existence of such opsins in C. reinhardtii and V. carteri and show that they have cytosolic N- and C-termini, implying an eight-transmembrane helix structure. We also demonstrate that cGMP production is both light-inhibited and ATP-dependent. The cyclase activity of Cr2c-Cyclop1 is kept functional by the ongoing phosphorylation and phosphoryl transfer from the histidine kinase to the response regulator in the dark, proven by mutagenesis. Absorption of a photon inhibits the cyclase activity, most likely by inhibiting the phosphoryl transfer. Overexpression of Vc2c-Cyclop1 protein in V. carteri leads to significantly increased cGMP levels, demonstrating guanylyl cyclase activity of Vc2c-Cyclop1 in vivo. Live cell imaging of YFP-tagged Vc2c-Cyclop1 in V. carteri revealed a development-dependent, layer-like structure at the immediate periphery of the nucleus and intense spots in the cell periphery.

CONCLUSIONS: Cr2c-Cyclop1 and Vc2c-Cyclop1 are light-inhibited and ATP-dependent guanylyl cyclases with an unusual eight-transmembrane helix structure of the type I opsin domain which we propose to classify as type Ib, in contrast to the 7 TM type Ia opsins. Overexpression of Vc2c-Cyclop1 protein in V. carteri led to a significant increase of cGMP, demonstrating enzyme functionality in the organism of origin. Fluorescent live cell imaging revealed that Vc2c-Cyclop1 is located in the periphery of the nucleus and in confined areas at the cell periphery.}, } @article {pmid30522452, year = {2018}, author = {Velasco-Arroyo, B and Martinez, M and Diaz, I and Diaz-Mendoza, M}, title = {Differential response of silencing HvIcy2 barley plants against Magnaporthe oryzae infection and light deprivation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {337}, pmid = {30522452}, issn = {1471-2229}, support = {BIO2014-53508-R//MINECO/ ; }, mesh = {Cysteine Proteases/metabolism ; Gene Expression Regulation, Plant ; *Gene Silencing ; Genes, Plant/genetics ; Hordeum/genetics/metabolism/microbiology/*physiology ; Light ; *Magnaporthe ; Plant Diseases/immunology/*microbiology ; Plant Proteins/genetics/metabolism ; Plants, Genetically Modified ; }, abstract = {BACKGROUND: Phytocystatins (PhyCys) act as endogenous regulators of cysteine proteases (CysProt) involved in various physiological processes. Besides, PhyCys are involved in plant reactions to abiotic stresses like drought or darkness and have been used as effective molecules against different pests and pathogens. The barley PhyCys-CysProt system is considered a model of protease-inhibitor regulation of protein turnover. Thirteen barley cystatins (HvCPI-1 to HvCPI-13) have been previously identified and characterized. Among them HvCPI-2 has been shown to have a relevant role in plant responses to pathogens and pests, as well as in the plant response to drought.

RESULTS: The present work explores the multiple role of this barley PhyCys in response to both, biotic and abiotic stresses, focusing on the impact of silencing this gene. HvIcy-2 silencing lines behave differentially against the phytopathogenic fungus Magnaporthe oryzae and a light deprivation treatment. The induced expression of HvIcy-2 by the fungal stress correlated to a higher susceptibility of silencing HvIcy-2 plants. In contrast, a reduction in the expression of HvIcy-2 and in the cathepsin-L and -B like activities in the silencing HvIcy-2 plants was not accompanied by apparent phenotypical differences with control plants in response to light deprivation.

CONCLUSION: These results highlight the specificity of PhyCys in the responses to diverse external prompts as well as the complexity of the regulatory events leading to the response to a particular stress. The mechanism of regulation of these stress responses seems to be focused in maintaining the balance of CysProt and PhyCys levels, which is crucial for the modulation of physiological processes induced by biotic or abiotic stresses.}, } @article {pmid30522448, year = {2018}, author = {Ma, J and Geng, Y and Pei, W and Wu, M and Li, X and Liu, G and Li, D and Ma, Q and Zang, X and Yu, S and Zhang, J and Yu, J}, title = {Genetic variation of dynamic fiber elongation and developmental quantitative trait locus mapping of fiber length in upland cotton (Gossypium hirsutum L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {882}, pmid = {30522448}, issn = {1471-2164}, support = {2016YFD0101400//the National Key Research and Development Program of China/ ; 2016ZX08005005//the National Research and Development Project of Transgenic Crops of China/ ; 31621005//the National Natural Science Foundation of China/ ; 31701474//the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: In upland cotton (Gossypium hirsutum L.), genotypes with the same mature fiber length (FL) might possess different genes and exhibit differential expression of genes related to fiber elongation at different fiber developmental stages. However, there is a lack of information on the genetic variation influencing fiber length and its quantitative trait loci (QTLs) during the fiber elongation stage. In this study, a subset of upland cotton accessions was selected based on a previous GWAS conducted in China and grown in multiple environments to determine the dynamic fiber length at 10, 15, 20, and 25 days post-anthesis (DPA) and maturity. The germplasm lines were genotyped with the Cotton 63 K Illumina single-nucleotide polymorphism (SNP) array for GWAS.

RESULTS: A total of 25, 38, 57, 89 and 88 SNPs showed significant correlations with fiber length at 10, 15, 20 and 25 DPA and maturity, respectively. In addition, 60 more promising SNPs were detected in at least two tests and two FL developmental time points, and 20 SNPs were located within the confidence intervals of QTLs identified in previous studies. The fastest fiber-length growth rates were obtained at 10 to 15 DPA in 69 upland cotton lines and at 15 to 20 DPA in 14 upland cotton accessions, and 10 SNPs showed significant correlations with the fiber-length growth rate. A combined transcriptome and qRT-PCR analysis revealed that two genes (D10G1008 and D13G2037) showed differential expression between two long-fiber genotypes and two short-fiber genotypes.

CONCLUSIONS: This study provides important new insights into the genetic basis of the time-dependent fiber-length trait and reveals candidate SNPs and genes for improving fiber length in upland cotton.}, } @article {pmid30522443, year = {2018}, author = {Boone, K and Camarda, K and Spencer, P and Tamerler, C}, title = {Antimicrobial peptide similarity and classification through rough set theory using physicochemical boundaries.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {469}, pmid = {30522443}, issn = {1471-2105}, support = {R01 DE025476/DE/NIDCR NIH HHS/United States ; R01 DE022054//National Institute of Dental and Craniofacial Research/ ; DE025476//National Institute of Dental and Craniofacial Research/ ; AR062249-03//National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; }, mesh = {Antimicrobial Cationic Peptides/*classification/metabolism ; *Chemical Phenomena ; Models, Molecular ; }, abstract = {BACKGROUND: Antimicrobial peptides attract considerable interest as novel agents to combat infections. Their long-time potency across bacteria, viruses and fungi as part of diverse innate immune systems offers a solution to overcome the rising concerns from antibiotic resistance. With the rapid increase of antimicrobial peptides reported in the databases, peptide selection becomes a challenge. We propose similarity analyses to describe key properties that distinguish between active and non-active peptide sequences building upon the physicochemical properties of antimicrobial peptides. We used an iterative supervised machine learning approach to classify active peptides from inactive peptides with low false discovery rates in a relatively short computational search time.

RESULTS: By generating explicit boundaries, our method defines new categories of active and inactive peptides based on their physicochemical properties. Consequently, it describes physicochemical characteristics of similarity among active peptides and the physicochemical boundaries between active and inactive peptides in a single process. To build the similarity boundaries, we used the rough set theory approach; to our knowledge, this is the first time that this approach has been used to classify peptides. The modified rough set theory method limits the number of values describing a boundary to a user-defined limit. Our method is optimized for specificity over selectivity. Noting that false positives increase activity assays while false negatives only increase computational search time, our method provided a low false discovery rate. Published datasets were used to compare our rough set theory method to other published classification methods and based on this comparison, we achieved high selectivity and comparable sensitivity to currently available methods.

CONCLUSIONS: We developed rule sets that define physicochemical boundaries which allow us to directly classify the active sequences from inactive peptides. Existing classification methods are either sequence-order insensitive or length-dependent, whereas our method generates the rule sets that combine order-sensitive descriptors with length-independent descriptors. The method provides comparable or improved performance to currently available methods. Discovering the boundaries of physicochemical properties may lead to a new understanding of peptide similarity.}, } @article {pmid30522441, year = {2018}, author = {Gidoin, C and Ujvari, B and Thomas, F and Roche, B}, title = {How is the evolution of tumour resistance at organ-scale impacted by the importance of the organ for fitness?.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {185}, pmid = {30522441}, issn = {1471-2148}, mesh = {*Biological Evolution ; Computer Simulation ; Humans ; Incidence ; Models, Biological ; Neoplasm Metastasis ; Neoplasms/*pathology ; *Organ Specificity ; Reproduction ; }, abstract = {BACKGROUND: A strong variability in cancer incidence is observed between human organs. Recently, it has been suggested that the relative contribution of organs to organism fitness (reproduction or survival) could explain at least a part of the observed variation. The objective of this study is to investigate theoretically the main factors driving the evolution of tumour resistance mechanisms of organs when their relative contribution to organism fitness is considered. We use a population-scale model where individuals can develop a tumour in a key organ (i.e. in which even a small tumour can negatively impact organism fitness), an auxiliary organ (i.e. in which only a large tumour has a relatively significant impact) or both organs because of metastasis.

RESULTS: Our simulations show that natural selection acts in two different ways to prevent cancer in a key and an auxiliary organs. In the key organ, the strategy mostly selected is the highest resistance and only a high cost of resistance mitigates this behavior. Inversely, we observe that a low resistance strategy can be selected in the auxiliary organ when the development of the tumour is slow and the effect of a large tumour on the mortality of the organism is relatively weak. Nevertheless, if the tumour can spread to a key organ, higher resistance strategies are selected in the auxiliary organ.

CONCLUSION: Finally, our study demonstrates that the relative contribution of organs to the organism fitness and the metastatic propensity of the tumour influence the evolution of tumour resistance at organ scale and should be considered by studies aiming to explain the variability in cancer incidence at organ-scale.}, } @article {pmid30522439, year = {2018}, author = {Zahariev, M and Chen, W and Visagie, CM and Lévesque, CA}, title = {Cluster oligonucleotide signatures for rapid identification by sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {395}, pmid = {30522439}, issn = {1471-2105}, support = {97//Agriculture and Agri-Food Canada (CA)/ ; CRTI 09-462RD/CSSP 30vv01//Canadian safety and security program (CSSP), CA/ ; }, mesh = {High-Throughput Nucleotide Sequencing/*methods ; Metagenomics/*methods ; Oligonucleotides/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Oligonucleotide signatures (signatures) have been widely used for studying microbial diversity and function in wet-lab settings, but using them for accurate in silico identification of organisms from high-throughput sequencing (HTS) data is only a proof of concept. Existing signature design programs for sequence signatures (signatures matching exactly one sequence) or clade signatures (signatures matching every sequence in a phylogenetic clade) are not able to identify all possible polymorphic sites for sequences with high similarity and perform poorly when handling large genome sequencing datasets.

RESULTS: We introduce cluster signatures: subsequences that match perfectly and exclusively any group of sequences in a data set. Cluster signatures provide complete recall for primer/probe design and increased discrimination between sequences beyond that of clade signatures. Using cluster signatures for in silico identification of HTS targets achieves good precision/recall and running time performance. This method has been implemented into an open source tool, the Automated Oligonucleotide Design Pipeline (adop), included in supplementary material and available at: https://bitbucket.org/wenchen_aafc/aodp_v2.0_release .

CONCLUSIONS: Cluster signatures provide a rapid and universal analysis tool to identify all possible short diagnostic DNA markers and variants from any DNA sequencing dataset. They are particularly useful in discriminating genetic material from closely related organisms and in detecting deleterious mutations in highly or perfectly conserved genomic sites.}, } @article {pmid30522437, year = {2018}, author = {Ali, I and Teng, Z and Bai, Y and Yang, Q and Hao, Y and Hou, J and Jia, Y and Tian, L and Liu, X and Tan, Z and Wang, W and Kenneth, K and Sharkh, AYA and Liu, D and Guo, K and Zhang, J and Liu, D and Zhang, Z}, title = {A high density SLAF-SNP genetic map and QTL detection for fibre quality traits in Gossypium hirsutum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {879}, pmid = {30522437}, issn = {1471-2164}, support = {31571720, 31371671//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Upland Cotton (Gossypium hirsutum) is a very important cash crop known for its high quality natural fiber. Recent advances in sequencing technologies provide powerful tools with which to explore the cotton genome for single nucleotide polymorphism marker identification and high density genetic map construction toward more reliable quantitative trait locus mapping.

RESULTS: In the present study, a RIL population was developed by crossing a Chinese high fiber quality cultivar (Yumian 1) and an American high fiber quality line (CA3084), with distinct genetic backgrounds. Specific locus amplified fragment sequencing (SLAF-seq) technology was used to discover SNPs, and a genetic map containing 6254 SNPs was constructed, covering 3141.72 cM with an average distance of 0.5 cM between markers. A total of 95 QTL were detected for fiber quality traits in three environments, explaining 5.5-24.6% of the phenotypic variance. Fifty-five QTL found in multiple environments were considered stable QTL. Nine of the stable QTL were found in all three environments. We identified 14 QTL clusters on 13 chromosomes, each containing one or more stable QTL.

CONCLUSION: A high-density genetic map of Gossypium hirsutum developed by using specific locus amplified fragment sequencing technology provides detailed mapping of fiber quality QTL, and identification of 'stable QTL' found in multiple environments. A marker-rich genetic map provides a foundation for fine mapping, candidate gene identification and marker-assisted selection of favorable alleles at stable QTL in breeding programs.}, } @article {pmid30522435, year = {2018}, author = {Bi, K and Chen, T and He, Z and Gao, Z and Zhao, Y and Fu, Y and Cheng, J and Xie, J and Jiang, D}, title = {Proto-oncogenes in a eukaryotic unicellular organism play essential roles in plasmodial growth in host cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {881}, pmid = {30522435}, issn = {1471-2164}, support = {No. 2017YFD0200600//National Key R&D Program/ ; No. 2662015PY117//Fundamental Research Funds for the Central Universities/ ; CARS-13//the earmarked fund for China Agriculture Research System/ ; }, abstract = {BACKGROUND: The eukaryotic unicellular protist Plasmodiophora brassicae is an endocellular parasite of cruciferous plants. In host cortical cells, this protist develops a unicellular structure that is termed the plasmodium. The plasmodium is actually a multinucleated cell, which subsequently splits and forms resting spores. The mechanism for the growth of this endocellular parasite in host cell is unclear.

RESULTS: Here, combining de novo genome sequence and transcriptome analysis of strain ZJ-1, we identified top five significant enriched KEGG pathways of differentially expressed genes (DEGs), namely translation, cell growth and death, cell communication, cell motility and cancers. We detected 171 proto-oncogenes from the genome of P. brassicae that were implicated in cancer-related pathways, of which 46 were differential expression genes. Three predicted proto-oncogenes (Pb-Raf1, Pb-Raf2, and Pb-MYB), which showed homology to the human proto-oncogenes Raf and MYB, were specifically activated during the plasmodial growth in host cortical cells, demonstrating their involvement in the multinucleate development stage of the unicellular protist organism. Gene networks involved in the tumorigenic-related signaling transduction pathways and the activation of 12 core genes were identified. Inhibition of phosphoinositol-3-kinase relieved the clubroot symptom and significantly suppressed the development process of plasmodia.

CONCLUSIONS: Proto-oncogene-related regulatory mechanisms play an important role in the plasmodial growth of P. brassicae.}, } @article {pmid30522433, year = {2018}, author = {Mohr, T and Aliyu, H and Küchlin, R and Zwick, M and Cowan, D and Neumann, A and de Maayer, P}, title = {Comparative genomic analysis of Parageobacillus thermoglucosidasius strains with distinct hydrogenogenic capacities.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {880}, pmid = {30522433}, issn = {1471-2164}, support = {031B0180//Bundesministerium für Bildung und Forschung/ ; }, abstract = {BACKGROUND: The facultatively anaerobic thermophile Parageobacillus thermoglucosidasius produces hydrogen gas (H2) by coupling CO oxidation to proton reduction in the water-gas shift (WGS) reaction via a carbon monoxide dehydrogenase-hydrogenase enzyme complex. Although little is known about the hydrogenogenic capacities of different strains of this species, these organisms offer a potentially viable process for the synthesis of this alternative energy source.

RESULTS: The WGS-catalyzed H2 production capacities of four distinct P. thermoglucosidasius strains were determined by cultivation and gas analysis. Three strains (DSM 2542T, DSM 2543 and DSM 6285) were hydrogenogenic, while the fourth strain (DSM 21625) was not. Furthermore, in one strain (DSM 6285) H2 production commenced earlier in the cultivation than the other hydrogenogenic strains. Comparative genomic analysis of the four strains identified extensive differences in the protein complement encoded on the genomes, some of which are postulated to contribute to the different hydrogenogenic capacities of the strains. Furthermore, polymorphisms and deletions in the CODH-NiFe hydrogenase loci may also contribute towards this variable phenotype.

CONCLUSIONS: Disparities in the hydrogenogenic capacities of different P. thermoglucosidasius strains were identified, which may be correlated to variability in their global proteomes and genetic differences in their CODH-NiFe hydrogenase loci. The data from this study may contribute towards an improved understanding of WGS-catalysed hydrogenogenesis by P. thermoglucosidasius.}, } @article {pmid30522432, year = {2018}, author = {Liu, N and Dong, L and Deng, X and Liu, D and Liu, Y and Li, M and Hu, Y and Yan, Y}, title = {Genome-wide identification, molecular evolution, and expression analysis of auxin response factor (ARF) gene family in Brachypodium distachyon L.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {336}, pmid = {30522432}, issn = {1471-2229}, mesh = {Biological Evolution ; Brachypodium/*genetics/metabolism ; Chromosome Mapping ; Chromosomes, Plant/genetics ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/*genetics ; Genome-Wide Association Study ; Indoleacetic Acids/*metabolism ; Phylogeny ; Plant Growth Regulators/*metabolism ; Plant Proteins/*genetics/metabolism ; Promoter Regions, Genetic/genetics ; Transcription Factors/*genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: The auxin response factor (ARF) gene family is involved in plant development and hormone regulation. Although the ARF gene family has been studied in some plant species, its structural features, molecular evolution, and expression profiling in Brachypodium distachyon L. are still not clear.

RESULTS: Genome-wide analysis identified 19 ARF genes in B. distachyon. A phylogenetic tree constructed with 182 ARF genes from seven plant species revealed three different clades, and the ARF genes from within a clade exhibited structural conservation, although certain divergences occurred in different clades. The branch-site model identified some sites where positive selection may have occurred, and functional divergence analysis found more Type II divergence sites than Type I. In particular, both positive selection and functional divergence may have occurred in 241H, 243G, 244 L, 310 T, 340G and 355 T. Subcellular localization prediction and experimental verification indicated that BdARF proteins were present in the nucleus. Transcript expression analysis revealed that BdARFs were mainly expressed in the leaf and root tips, stems, and developing seeds. Some BdARF genes exhibited significantly upregulated expression under various abiotic stressors. Particularly, BdARF4 and BdARF8 were significantly upregulated in response to abiotic stress factors such as salicylic acid and heavy metals.

CONCLUSION: The ARF gene family in B. distachyon was highly conserved. Several important amino acid sites were identified where positive selection and functional divergence occurred, and they may play important roles in functional differentiation. BdARF genes had clear tissue and organ expression preference and were involved in abiotic stress response, suggesting their roles in plant growth and stress resistance.}, } @article {pmid30540290, year = {2018}, author = {Tran Ngoc, C and Bigirimana, N and Muneene, D and Bataringaya, JE and Barango, P and Eskandar, H and Igiribambe, R and Sina-Odunsi, A and Condo, JU and Olu, O}, title = {Conclusions of the digital health hub of the Transform Africa Summit (2018): strong government leadership and public-private-partnerships are key prerequisites for sustainable scale up of digital health in Africa.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 11}, pages = {17}, pmid = {30540290}, issn = {1753-6561}, abstract = {Background: The use of digital technologies to improve access to health is gaining momentum in Africa. This is more pertinent with the increasing penetration of mobile phone technology and internet use, and calls for innovative strategies to support implementation of the health-related Sustainable Development Goals and Universal Health Coverage on the continent. However, the huge potential benefits of digital health to advance health services delivery in Africa is yet to be fully harnessed due to critical challenges such as proliferation of pilot projects, poor coordination, inadequate preparedness of the African health workforce for digital health, lack of interoperability and inadequate sustainable financing, among others. To discuss these challenges and propose the way forward for rapid, cost-effective and sustainable deployment of digital health in Africa, a Digital Health Hub was held in Kigali from 8th to 9th May 2018 under the umbrella of the Transform Africa Summit 2018.

Methods: The hub was organized around five thematic areas which explored the status, leadership, innovations, sustainable financing of digital health and its deployment for prevention and control of Non-Communicable Diseases in Africa. It was attended by over 200 participants from Ministries of Health and Information and Communication Technology, Private Sector, Operators, International Organizations, Civil Society and Academia.

Conclusions: The hub concluded that while digital health offers major opportunities for strengthening health systems towards the attainment of the Sustainable Development Goals including Universal Health Coverage in Africa, there is need to move from Donor-driven pilot projects to more sustainable and longer term nationally owned programmes to reap its benefits. This would require the use of people-centred approaches which are demand, rather than supply-driven in order to avoid fragmentation and wastage of health resources. Government leadership is also critical in ensuring the availability of an enabling environment including national digital health strategies, regulatory, coordination, sustainable financing mechanisms and building of the necessary partnerships for digital health.

Recommendations: We call on the Smart Africa Secretariat, African Ministries in charge of health, information and communication technology and relevant stakeholders to ensure that the key recommendations of the hub are implemented.}, } @article {pmid30540288, year = {2018}, author = {Galica, J and Chee-A-Tow, A and Gupta, S and Jaiswal, A and Monsour, A and Tricco, AC and Cobey, KD and Butcher, NJ}, title = {Learning best-practices in journalology: course description and attendee insights into the inaugural EQUATOR Canada Publication School.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 10}, pages = {18}, pmid = {30540288}, issn = {1753-6561}, abstract = {Background and purpose: Dissemination of research results is a key component of the research continuum and is commonly achieved through publication in peer-reviewed academic journals. However, issues of poor quality reporting in the research literature are well documented. A lack of formal training in journalology (i.e., publication science) may contribute to this problem. To help address this gap in training, the Enhancing the QUAlity and Transparency Of health Research (EQUATOR) Canada Publication School was developed and facilitated by internationally-renowned faculty to train researchers and clinicians in reporting and publication best practices. This article describes the structure of the inaugural course and provides an overview of attendee evaluations and perspectives.

Key highlights: Attendees perceived the content of this two-day intensive course as highly informative. They noted that the course helped them learn skills that were relevant to academic publishing (e.g., using reporting guidelines in all phases of the research process; using scholarly metrics beyond the journal impact factor; open-access publication models; and engaging patients in the research process). The course provided an opportunity for researchers to share their challenges faced during the publication process and to learn skills for improving reproducibility, completeness, transparency, and dissemination of research results. There was some suggestion that this type of course should be offered and integrated into formal training and course curricula.

Implications: In light of the importance of academic publishing in the scientific process, there is a need to train and prepare researchers with skills in Journalology. The EQUATOR Canada Publication School provides an example of a successful program that addressed the needs of researchers across career trajectories and provided them with resources to be successful in the publication process. This approach can be used, modified, and/or adapted by curriculum developers interested in designing similar programs, and could be incorporated into academic and clinical research training programs.}, } @article {pmid30540245, year = {2018}, author = {Xiao, M and Zhou, XK and Chen, X and Duan, YQ and Alkhalifah, DHM and Im, WT and Hozzein, WN and Chen, W and Li, WJ}, title = {Lysobacter tabacisoli sp. nov., isolated from rhizosphere soil of Nicotiana tabacum L.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003164}, pmid = {30540245}, issn = {1466-5034}, abstract = {A Gram-stain-negative, aerobic, rod-shaped bacterium, designated strain C8-1T, was isolated from the rhizosphere soil of Nicotiana tabacum L. collected from Kunming, south-west China. The cells showed oxidase-positive and catalase-positive reactions. Growth was observed at 10-40 °C, at pH 6.0-8.0 and in the presence of up to 1 % (w/v) NaCl, with optimal growth at 30 °C and pH 7.0. The predominant isoprenoid quinone was Q-8. The major fatty acids were identified as iso-C15 : 0, iso-C17 : 0 and iso-C17 : 1ω9c. The cellular polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, five unidentified phospholipids and two unidentified aminophospholipids. The genomic DNA G+C content was 70.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain C8-1T should be assigned to the genus Lysobacter. 16S rRNA gene sequence similarity analysis showed that strain C8-1T was closely related to Lysobacter cavernae YIM C01544T (98.6 %), Lysobacter soli DCY21T (97.6 %), Lysobacter panacisoli CJ29T (97.3 %), Lysobacter firmicutimachus PB-6250T (97.3 %), Lysobacter niastensis GH41-7T (97.3 %) and Lysobacter gummosus KCTC 12132T (97.1 %). DNA-DNA hybridization data indicated that the isolate may represent a novel genomic species belonging to the genus Lysobacter. Polyphasic taxonomic characteristics indicated that strain C8-1T represents a novel species of the genus Lysobacter, for which the name Lysobacter tabacisoli sp. nov. is proposed. The type strain is C8-1T (=KCTC 62034T=CGMCC 1.16271T) .}, } @article {pmid30540242, year = {2018}, author = {Lee, SD}, title = {Lutibaculum pontilimi sp. nov., isolated from a tidal mudflat and emended description of the genus Lutibaculum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003163}, pmid = {30540242}, issn = {1466-5034}, abstract = {A novel Gram-reaction-negative bacterium, designated strain GH1-34T, was isolated from a sample of tidal mudflat collected at the seashore of Gangwha Island, Republic of Korea. Cells of the bacterium were strictly aerobic, catalase- and oxidase-positive, motile by means of a polar flagellum and rod shaped. It was found to grow at 0-5 % (w/v) NaCl, 20-45 °C and pH 6-10. The major isoprenoid quinone was Q-10. The polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminolipid and an unidentified glycolipid. The predominant fatty acids were C18 : 1ω7c and C19 : 0cyclo ω8c. The G+C content of the DNA was 70.9 mol%. Comparative 16S rRNA gene sequence analysis revealed that strain GH1-34T formed a tight cluster with the type strain of Lutibaculum baratangense with 98.3 % sequence similarity; levels of the 16S rRNA gene sequence similarity between the novel strain and other representatives of the order 'Rhizobiales' were <95.0 %. DNA-DNA relatedness between the organism and L. baratangense KCTC 22669T was 33 %, Based on the results of phenotypic analysis and DNA-DNA hybridization experiments, strain GH1-34T (=KCTC 52847T=NBRC 113277T) represents a novel species of the genus Lutibaculum, for which the name Lutibaculum pontilimi sp. nov. is proposed.}, } @article {pmid30540241, year = {2018}, author = {Chen, Z and Tian, W and Sun, F and Chen, Y and Han, H and Yao, L and Zhang, Z}, title = {Pedobacter miscanthi sp. nov., isolated from Miscanthus sinensis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003161}, pmid = {30540241}, issn = {1466-5034}, abstract = {In a survey of endophytic bacteria in Miscanthus sinensis, a strain of Gram-negative, non-endospore-forming, rod-shaped, aerobic bacterium was isolated and designated as RS10T. Phylogenetic analysis based on its 16S rRNA gene sequence showed that the strain RS10T was affiliated with the genus Pedobacter and exhibited the highest sequence similarities to Pedobacter kyungheensis KACC 16221T (97.78 %), Pedobacter roseus KCTC 22187T (97.75 %), Pedobacter humicola KACC 18452T (97.29 %) and Pedobacter soli KACC 14939T (97.23 %). The novel strain contained iso-C15 : 0, iso-C17 : 0-3OH and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) as major fatty acids. The only isoprenoid quinone detected in strain RS10T was MK-7. Strain RS10T contains phosphatidylethanolamine and one kind of aminophospholipid as its major polar lipids. The DNA G+C content for RS10T was 39.8 mol%. Based on the results of phenotypic and genomic characterizations, we concluded that strains RS10T represents a novel species of Pedobacter, for which the name Pedobacter miscanthi sp. nov. is proposed. The type strain is RS10T (=KCTC 62786T=GDMCC 1.1415T).}, } @article {pmid30540240, year = {2018}, author = {Kobayashi, H and Tanizawa, Y and Sakamoto, M and Nakamura, Y and Ohkuma, M and Tohno, M}, title = {Reclassification of Paenibacillus thermophilus Zhou et al. 2013 as a later heterotypic synonym of Paenibacillus macerans (Schardinger 1905) Ash et al. 1994.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003160}, pmid = {30540240}, issn = {1466-5034}, abstract = {The taxonomic status of Paenibacillus thermophilus was analyzed using genomic and phenotypic approaches. The results of RNA polymerase beta subunit gene sequence comparisons indicated that two type strains of P. thermophilus (DSM 24746T and JCM 17693T) and Paenibacillus macerans ATCC 8244T shared 100 % sequence similarity. By whole-genome sequence comparison, their average nucleotide identity values were over 99.3 %. Investigation of substrate utilization, enzyme activities and cellular fatty acid patterns displayed no striking differences between P. thermophilus JCM 17693T and P. macerans JCM 2500T. On the basis of these results, we propose that the name Paenibacillus thermophilus is a later heterotypic synonym of Paenibacillus macerans.}, } @article {pmid30540239, year = {2018}, author = {Cao, P and Wang, Y and Sun, P and Li, C and Zhao, J and Jiang, S and Zhang, Y and Wang, X and Xiang, W}, title = {Nonomuraea lactucae sp. nov., a novel actinomycete isolated from rhizosphere soil of lettuce (Lactuca sativa).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003113}, pmid = {30540239}, issn = {1466-5034}, abstract = {A novel actinobacterium, designated strain NEAU-YG30T, was isolated from the rhizosphere soil of lettuce collected in Heilongjiang province, north-east China. The taxonomic position of the strain was investigated using a polyphasic approach. On the basis of 16S rRNA gene sequence analysis, strain NEAU-YG30T belongs to the genus Nonomuraea, and shared highest sequence similarity to Nonomuraea muscovyensis KCTC 29233T (97.9 %) and Nonomuraea indica CCTCC AA 209050T (97.6 %). The major menaquinone was identified as MK-9(H4). The major fatty acids were 10-methyl C17 : 0, C17 : 0, iso-C16 : 0 2-OH, iso-C16 : 0 and C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, hydroxyl-phosphatidylethanolamine, phosphatidylinositol, an unidentified phospholipid and three unidentified lipids. The genomic DNA G+C content of strain NEAU-YG30T was 70.5 mol%. DNA-DNA hybridization values between them were less than 70 %. On the basis of phenotypic, genotypic and phylogenetic data, strain NEAU-YG30T can be characterized to represent a novel species of the genus Nonomuraea, for which the name Nonomuraealactucae sp. nov. is proposed. The type strain is NEAU-YG30T (=JCM 32549T=CGMCC 4.7506T).}, } @article {pmid30540238, year = {2018}, author = {Altamia, MA and Shipway, JR and Concepcion, GP and Haygood, MG and Distel, DL}, title = {Thiosocius teredinicola gen. nov., sp. nov., a sulfur-oxidizing chemolithoautotrophic endosymbiont cultivated from the gills of the giant shipworm, Kuphus polythalamius.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003143}, pmid = {30540238}, issn = {1466-5034}, abstract = {A chemolithoautotrophic sulfur-oxidizing, diazotrophic, facultatively heterotrophic, endosymbiotic bacterium, designated as strain 2141T, was isolated from the gills of the giant shipworm Kuphus polythalamius (Teredinidae: Bivalvia). Based on its 16S rRNA sequence, the endosymbiont falls within a clade that includes the as-yet-uncultivated thioautotrophic symbionts of a marine ciliate and hydrothermal vent gastropods, uncultivated marine sediment bacteria, and a free-living sulfur-oxidizing bacterium ODIII6, all of which belong to the Gammaproteobacteria. The endosymbiont is Gram-negative, rod-shaped and has a single polar flagellum when grown in culture. This bacterium can be grown chemolithoautotrophically on a chemically defined medium supplemented with either hydrogen sulfide, thiosulfate, tetrathionate or elemental sulfur. The closed-circular genome has a DNA G+C content of 60.1 mol% and is 4.79 Mbp in size with a large nitrogenase cluster spanning nearly 40 kbp. The diazotrophic capability was confirmed by growing the strain on chemolithoautotrophic thiosulfate-based medium without a combined source of fixed nitrogen. The bacterium is also capable of heterotrophic growth on organic acids such as acetate and propionate. The pH, temperature and salinity optima for chemolithoautotrophic growth on thiosulfate were found to be 8.5, 34 °C and 0.2 M NaCl, respectively. To our knowledge, this is the first report of pure culture of a thioautotrophic animal symbiont. The type strain of Thiosocius teredinicola is PMS-2141T.STBD.0c.01aT (=DSM 108030T).}, } @article {pmid30540237, year = {2018}, author = {Sun, YT and Zhou, N and Wang, BJ and Liu, XD and Jiang, CY and Ge, X and Liu, SJ}, title = {Vallitalea okinawensis sp. nov., isolated from Okinawa Trough sediment and emended description of the genus Vallitalea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003158}, pmid = {30540237}, issn = {1466-5034}, abstract = {A polyphasic study was conducted to characterize an obligately anaerobic bacterial strain, S15T, that was isolated from Okinawa Trough sediment. Strain S15T was Gram-stain-negative, non-motile and rod-shaped. Spores were not observed. Strain S15T grew anaerobically at 20-35 °C (optimum at 25-30 °C) and at pH range of 6.0-8.5 (optimum at 7.5). Analysis of 16S rRNA gene sequences showed that strain S15T was phylogenetically related to Vallitalea guaymasensis Ra1766G1T (94.0 %) and Vallitalea pronyensis FatNI3T (93.1 %). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipids. The predominant fatty acids of strain S15T were iso-C15 : 0, anteiso-C15 : 0, iso-C16 : 0 and C16 : 0. The draft genome was 5.86 Mb with a DNA G+C content of 33.9 mol %. A total of 5285 genes were predicted and, of those, 4669 genes were annotated. The genome data supported the result that strain S15T assimilated various carbon sources. On the basis of unique phenotypic, chemotaxonomic and phylogenetic comparisons, strain S15T is proposed to represent a novel species within the genus Vallitalea, and the name Vallitaleaokinawensis sp. nov. is proposed. The type strain is S15T=CGMCC 1.5231T=KCTC 15675T.}, } @article {pmid30539716, year = {2019}, author = {Syed, A and Lukacsovich, T and Pomeroy, M and Bardwell, AJ and Decker, GT and Waymire, KG and Purcell, J and Huang, W and Gui, J and Padilla, EM and Park, C and Paul, A and Pham, TBT and Rodriguez, Y and Wei, S and Worthge, S and Zebarjedi, R and Zhang, B and Bardwell, L and Marsh, JL and MacGregor, GR}, title = {Miles to go (mtgo) encodes FNDC3 proteins that interact with the chaperonin subunit CCT3 and are required for NMJ branching and growth in Drosophila.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {37-53}, pmid = {30539716}, issn = {1095-564X}, support = {U01 HD045913/HD/NICHD NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; P40 OD010949/OD/NIH HHS/United States ; R21 HL102862/HL/NHLBI NIH HHS/United States ; R01 NS045283/NS/NINDS NIH HHS/United States ; P50 GM076516/GM/NIGMS NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; }, abstract = {Analysis of mutants that affect formation and function of the Drosophila larval neuromuscular junction (NMJ) has provided valuable insight into genes required for neuronal branching and synaptic growth. We report that NMJ development in Drosophila requires both the Drosophila ortholog of FNDC3 genes; CG42389 (herein referred to as miles to go; mtgo), and CCT3, which encodes a chaperonin complex subunit. Loss of mtgo function causes late pupal lethality with most animals unable to escape the pupal case, while rare escapers exhibit an ataxic gait and reduced lifespan. NMJs in mtgo mutant larvae have dramatically reduced branching and growth and fewer synaptic boutons compared with control animals. Mutant larvae show normal locomotion but display an abnormal self-righting response and chemosensory deficits that suggest additional functions of mtgo within the nervous system. The pharate lethality in mtgo mutants can be rescued by both low-level pan- and neuronal-, but not muscle-specific expression of a mtgo transgene, supporting a neuronal-intrinsic requirement for mtgo in NMJ development. Mtgo encodes three similar proteins whose domain structure is most closely related to the vertebrate intracellular cytosolic membrane-anchored fibronectin type-III domain-containing protein 3 (FNDC3) protein family. Mtgo physically and genetically interacts with Drosophila CCT3, which encodes a subunit of the TRiC/CCT chaperonin complex required for maturation of actin, tubulin and other substrates. Drosophila larvae heterozygous for a mutation in CCT3 that reduces binding between CCT3 and MTGO also show abnormal NMJ development similar to that observed in mtgo null mutants. Hence, the intracellular FNDC3-ortholog MTGO and CCT3 can form a macromolecular complex, and are both required for NMJ development in Drosophila.}, } @article {pmid30539407, year = {2018}, author = {Mikhaleva, EA and Leinsoo, TA and Ishizu, H and Gvozdev, VA and Klenov, MS}, title = {The nucleolar transcriptome regulates Piwi shuttling between the nucleolus and the nucleoplasm.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9595-y}, pmid = {30539407}, issn = {1573-6849}, support = {18-54-50015 YaPh_a//Russian Foundation for Basic Research/ ; }, abstract = {The nucleolus contains a lot of proteins unrelated to ribosome biogenesis. Some of these proteins shuttle between the nucleolus and the nucleoplasm regulating the cell cycle and stress response. The piRNA binding protein Piwi is involved in silencing of transposable elements (TEs) in the Drosophila gonads. Here we used cultured ovarian somatic cells (OSC) to characterize Piwi as a visitor to the nucleolus. Dynamic Piwi localization was shown to vary from its uniform distribution between the nucleoplasm and the nucleolus to pronounced nucleolar immobilization. We were intrigued by this localization behavior and revealed that nascent nucleolar transcripts recruit Piwi for nucleolar retention. Piwi eviction from the nucleolus was observed upon RNase treatment and after RNA polymerase (Pol) I inhibition, but not after Pol II inactivation. On the contrary, heat shock caused drastic Piwi redistribution from the nucleoplasm to the nucleolus, which occurred only in the presence of Pol I-mediated transcription. These results allow us to hypothesize that specific stress-induced transcripts made by Pol I promote the nucleolar sequestration of proteins in Drosophila, similar to previous observations in mammalian cells. We also found that in OSC, Piwi partially restricts expression of the rDNA copies containing R1 and R2 retrotransposon insertions especially upon heat shock-induced activation of these copies. Therefore, we suggest that Piwi intranuclear shuttling may have a functional role in ensuring a balance between silencing of rDNA-specific TEs under stress and the canonical Piwi function in non-nucleolar TE repression.}, } @article {pmid30539406, year = {2018}, author = {Ingles, ED and Deakin, JE}, title = {The methylation and telomere landscape in two families of marsupials with different rates of chromosome evolution.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {4}, pages = {317-332}, doi = {10.1007/s10577-018-9593-0}, pmid = {30539406}, issn = {1573-6849}, support = {DP160100187//Australian Research Council/ ; }, abstract = {Two marsupial families exemplify divergent rates of karyotypic change. The Dasyurid family has an extremely conserved karyotype. In contrast, there is significant chromosomal variation within the Macropodidae family, best exemplified by members of the genus Petrogale (rock-wallabies). Both families are also distinguished by their telomere landscape (length and epigenetics), with the dasyurids having a unique telomere length dimorphism not observed in other marsupials and hypothesised to be regulated in a parent-of-origin fashion. Previous work has shown that proximal ends of chromosomes are enriched in cytosine methylation in dasyurids, but that the chromosomes of a macropod, the tammar wallaby, have DNA methylation enrichment of pericentric regions. Using a combination of telomere and 5-methylcytosine immunofluorescence staining, we investigated the telomere landscape of four dasyurid and three Petrogale species. As part of this study, we also further examined the parent-of-origin hypothesis for the regulation of telomere length dimorphism in dasyurids, using epigenetic modifications known to differentiate the active maternal X chromosome, including 5-methylcytosine methylation and histone modifications H3K4me2, H3K9ac and H4Kac. Our results give further support to the parent-of-origin hypothesis for the regulation of telomere length dimorphism in dasyurids, where the paternally derived X chromosome in females was associated with long telomeres and the maternally derived with short telomeres. In contrast to the tammar wallaby, rock-wallabies demonstrated a similar 5-methylcytosine staining pattern across all chromosomes to that of dasyurids, suggesting that DNA methylation of telomeric regions is not responsible for differences in the rates of chromosome evolution between these two families.}, } @article {pmid30538323, year = {2018}, author = {Butler, D}, title = {Could the United Kingdom really build its own global satnav system?.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {172-173}, doi = {10.1038/d41586-018-07734-x}, pmid = {30538323}, issn = {1476-4687}, } @article {pmid30538322, year = {2018}, author = {}, title = {Wanted: a fair carbon tax.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {161}, doi = {10.1038/d41586-018-07717-y}, pmid = {30538322}, issn = {1476-4687}, } @article {pmid30538321, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {198}, doi = {10.1038/d41586-018-07679-1}, pmid = {30538321}, issn = {1476-4687}, } @article {pmid30538320, year = {2018}, author = {Rios Rojas, C}, title = {Students need guidance in languages they speak.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {163}, doi = {10.1038/d41586-018-07674-6}, pmid = {30538320}, issn = {1476-4687}, } @article {pmid30538319, year = {2018}, author = {Abbott, A}, title = {How the brain's face code might unlock the mysteries of perception.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {176-179}, doi = {10.1038/d41586-018-07668-4}, pmid = {30538319}, issn = {1476-4687}, } @article {pmid30538318, year = {2018}, author = {Payne, D}, title = {The scientists who feed us.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {293-294}, doi = {10.1038/d41586-018-07672-8}, pmid = {30538318}, issn = {1476-4687}, } @article {pmid30538317, year = {2018}, author = {}, title = {How to measure a superheavy atom.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {165}, doi = {10.1038/d41586-018-07626-0}, pmid = {30538317}, issn = {1476-4687}, } @article {pmid30538316, year = {2018}, author = {}, title = {Almost half a million mosquitoes are drafted to fight malaria.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {165}, doi = {10.1038/d41586-018-07664-8}, pmid = {30538316}, issn = {1476-4687}, } @article {pmid30538315, year = {2018}, author = {}, title = {Geckos slap their feet and swish their tails to race over water.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {164}, doi = {10.1038/d41586-018-07658-6}, pmid = {30538315}, issn = {1476-4687}, } @article {pmid30538314, year = {2018}, author = {}, title = {The cells that help cancer drugs to cloud the mind.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {165}, doi = {10.1038/d41586-018-07650-0}, pmid = {30538314}, issn = {1476-4687}, } @article {pmid30538313, year = {2018}, author = {}, title = {Epic storm roils a tranquil region of Neptune.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {165}, doi = {10.1038/d41586-018-07622-4}, pmid = {30538313}, issn = {1476-4687}, } @article {pmid30538312, year = {2018}, author = {}, title = {Genome of 'Lonesome George' reveals a tortoise's secrets to long life.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {164}, doi = {10.1038/d41586-018-07614-4}, pmid = {30538312}, issn = {1476-4687}, } @article {pmid30538311, year = {2018}, author = {}, title = {Mercury levels skyrocket thanks to Arctic warm up.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {164}, doi = {10.1038/d41586-018-07603-7}, pmid = {30538311}, issn = {1476-4687}, } @article {pmid30538306, year = {2018}, author = {Banerjee, S and Schlaeppi, K and van der Heijden, MGA}, title = {Reply to 'Can we predict microbial keystones?'.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0133-x}, pmid = {30538306}, issn = {1740-1534}, } @article {pmid30538210, year = {2018}, author = {Beans, C}, title = {News Feature: Targeting metastasis to halt cancer's spread.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12539-12543}, doi = {10.1073/pnas.1818892115}, pmid = {30538210}, issn = {1091-6490}, } @article {pmid30538209, year = {2019}, author = {Snyder-Mackler, N and Sanz, J and Kohn, JN and Voyles, T and Pique-Regi, R and Wilson, ME and Barreiro, LB and Tung, J}, title = {Social status alters chromatin accessibility and the gene regulatory response to glucocorticoid stimulation in rhesus macaques.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {4}, pages = {1219-1228}, doi = {10.1073/pnas.1811758115}, pmid = {30538209}, issn = {1091-6490}, support = {K99 AG051764/AG/NIA NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; R00 AG051764/AG/NIA NIH HHS/United States ; R01 AG057235/AG/NIA NIH HHS/United States ; T32 AG000139/AG/NIA NIH HHS/United States ; R01 GM102562/GM/NIGMS NIH HHS/United States ; }, abstract = {Low social status is an important predictor of disease susceptibility and mortality risk in humans and other social mammals. These effects are thought to stem in part from dysregulation of the glucocorticoid (GC)-mediated stress response. However, the molecular mechanisms that connect low social status and GC dysregulation to downstream health outcomes remain elusive. Here, we used an in vitro GC challenge to investigate the consequences of experimentally manipulated social status (i.e., dominance rank) for immune cell gene regulation in female rhesus macaques, using paired control and GC-treated peripheral blood mononuclear cell samples. We show that social status not only influences immune cell gene expression but also chromatin accessibility at hundreds of regions in the genome. Social status effects on gene expression were less pronounced following GC treatment than under control conditions. In contrast, social status effects on chromatin accessibility were stable across conditions, resulting in an attenuated relationship between social status, chromatin accessibility, and gene expression after GC exposure. Regions that were more accessible in high-status animals and regions that become more accessible following GC treatment were enriched for a highly concordant set of transcription factor binding motifs, including motifs for the GC receptor cofactor AP-1. Together, our findings support the hypothesis that social status alters the dynamics of GC-mediated gene regulation and identify chromatin accessibility as a mechanism involved in social stress-driven GC resistance. More broadly, they emphasize the context-dependent nature of social status effects on gene regulation and implicate epigenetic remodeling of chromatin accessibility as a contributing factor.}, } @article {pmid30538208, year = {2018}, author = {Lampe, RH and Mann, EL and Cohen, NR and Till, CP and Thamatrakoln, K and Brzezinski, MA and Bruland, KW and Twining, BS and Marchetti, A}, title = {Different iron storage strategies among bloom-forming diatoms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12275-E12284}, doi = {10.1073/pnas.1805243115}, pmid = {30538208}, issn = {1091-6490}, abstract = {Diatoms are prominent eukaryotic phytoplankton despite being limited by the micronutrient iron in vast expanses of the ocean. As iron inputs are often sporadic, diatoms have evolved mechanisms such as the ability to store iron that enable them to bloom when iron is resupplied and then persist when low iron levels are reinstated. Two iron storage mechanisms have been previously described: the protein ferritin and vacuolar storage. To investigate the ecological role of these mechanisms among diatoms, iron addition and removal incubations were conducted using natural phytoplankton communities from varying iron environments. We show that among the predominant diatoms, Pseudo-nitzschia were favored by iron removal and displayed unique ferritin expression consistent with a long-term storage function. Meanwhile, Chaetoceros and Thalassiosira gene expression aligned with vacuolar storage mechanisms. Pseudo-nitzschia also showed exceptionally high iron storage under steady-state high and low iron conditions, as well as following iron resupply to iron-limited cells. We propose that bloom-forming diatoms use different iron storage mechanisms and that ferritin utilization may provide an advantage in areas of prolonged iron limitation with pulsed iron inputs. As iron distributions and availability change, this speculated ferritin-linked advantage may result in shifts in diatom community composition that can alter marine ecosystems and biogeochemical cycles.}, } @article {pmid30538207, year = {2018}, author = {Leung, MR and van Bezouwen, LS and Schopfer, LM and Sussman, JL and Silman, I and Lockridge, O and Zeev-Ben-Mordehai, T}, title = {Cryo-EM structure of the native butyrylcholinesterase tetramer reveals a dimer of dimers stabilized by a superhelical assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13270-13275}, doi = {10.1073/pnas.1817009115}, pmid = {30538207}, issn = {1091-6490}, abstract = {The quaternary structures of the cholinesterases, acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), are essential for their localization and function. Of practical importance, BChE is a promising therapeutic candidate for intoxication by organophosphate nerve agents and insecticides, and for detoxification of addictive substances. Efficacy of the recombinant enzyme hinges on its having a long circulatory half-life; this, in turn, depends strongly on its ability to tetramerize. Here, we used cryoelectron microscopy (cryo-EM) to determine the structure of the highly glycosylated native BChE tetramer purified from human plasma at 5.7 Å. Our structure reveals that the BChE tetramer is organized as a staggered dimer of dimers. Tetramerization is mediated by assembly of the C-terminal tryptophan amphiphilic tetramerization (WAT) helices from each subunit as a superhelical assembly around a central lamellipodin-derived oligopeptide with a proline-rich attachment domain (PRAD) sequence that adopts a polyproline II helical conformation and runs antiparallel. The catalytic domains within a dimer are asymmetrically linked to the WAT/PRAD. In the resulting arrangement, the tetramerization domain is largely shielded by the catalytic domains, which may contribute to the stability of the human BChE (HuBChE) tetramer. Our cryo-EM structure reveals the basis for assembly of the native tetramers and has implications for the therapeutic applications of HuBChE. This mode of tetramerization is seen only in the cholinesterases but may provide a promising template for designing other proteins with improved circulatory residence times.}, } @article {pmid30538206, year = {2018}, author = {Harding, K and Turk-Kubo, KA and Sipler, RE and Mills, MM and Bronk, DA and Zehr, JP}, title = {Symbiotic unicellular cyanobacteria fix nitrogen in the Arctic Ocean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13371-13375}, doi = {10.1073/pnas.1813658115}, pmid = {30538206}, issn = {1091-6490}, abstract = {Biological dinitrogen (N2) fixation is an important source of nitrogen (N) in low-latitude open oceans. The unusual N2-fixing unicellular cyanobacteria (UCYN-A)/haptophyte symbiosis has been found in an increasing number of unexpected environments, including northern waters of the Danish Straight and Bering and Chukchi Seas. We used nanoscale secondary ion mass spectrometry (nanoSIMS) to measure 15N2 uptake into UCYN-A/haptophyte symbiosis and found that UCYN-A strains identical to low-latitude strains are fixing N2 in the Bering and Chukchi Seas, at rates comparable to subtropical waters. These results show definitively that cyanobacterial N2 fixation is not constrained to subtropical waters, challenging paradigms and models of global N2 fixation. The Arctic is particularly sensitive to climate change, and N2 fixation may increase in Arctic waters under future climate scenarios.}, } @article {pmid30538205, year = {2018}, author = {Voisin, T and Chiu, IM}, title = {Molecular link between itch and atopic dermatitis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12851-12853}, doi = {10.1073/pnas.1818879115}, pmid = {30538205}, issn = {1091-6490}, support = {DP2 AT009499/AT/NCCIH NIH HHS/United States ; }, mesh = {*Dermatitis, Atopic ; Humans ; *Mast Cells ; Membrane Proteins ; Musculoskeletal System ; Pruritus ; Surveys and Questionnaires ; }, } @article {pmid30538204, year = {2018}, author = {Yin, J and Chapman, K and Clark, LD and Shao, Z and Borek, D and Xu, Q and Wang, J and Rosenbaum, DM}, title = {Crystal structure of the human NK1 tachykinin receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13264-13269}, doi = {10.1073/pnas.1812717115}, pmid = {30538204}, issn = {1091-6490}, support = {R01 GM117080/GM/NIGMS NIH HHS/United States ; R01 GM079383/GM/NIGMS NIH HHS/United States ; R21 GM097617/GM/NIGMS NIH HHS/United States ; R01 NS103939/NS/NINDS NIH HHS/United States ; }, abstract = {The NK1 tachykinin G-protein-coupled receptor (GPCR) binds substance P, the first neuropeptide to be discovered in mammals. Through activation of NK1R, substance P modulates a wide variety of physiological and disease processes including nociception, inflammation, and depression. Human NK1R (hNK1R) modulators have shown promise in clinical trials for migraine, depression, and emesis. However, the only currently approved drugs targeting hNK1R are inhibitors for chemotherapy-induced nausea and vomiting (CINV). To better understand the molecular basis of ligand recognition and selectivity, we solved the crystal structure of hNK1R bound to the inhibitor L760735, a close analog of the drug aprepitant. Our crystal structure reveals the basis for antagonist interaction in the deep and narrow orthosteric pocket of the receptor. We used our structure as a template for computational docking and molecular-dynamics simulations to dissect the energetic importance of binding pocket interactions and model the binding of aprepitant. The structure of hNK1R is a valuable tool in the further development of tachykinin receptor modulators for multiple clinical applications.}, } @article {pmid30538203, year = {2018}, author = {Guinea, F and Walet, NR}, title = {Electrostatic effects, band distortions, and superconductivity in twisted graphene bilayers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13174-13179}, doi = {10.1073/pnas.1810947115}, pmid = {30538203}, issn = {1091-6490}, abstract = {Bilayer graphene twisted by a small angle shows a significant charge modulation away from neutrality, as the charge in the narrow bands near the Dirac point is mostly localized in a fraction of the Moiré unit cell. The resulting electrostatic potential leads to a filling-dependent change in the low-energy bands, of a magnitude comparable to or larger than the bandwidth. These modifications can be expressed in terms of new electron-electron interactions, which, when expressed in a local basis, describe electron-assisted hopping terms. These interactions favor superconductivity at certain fillings.}, } @article {pmid30538202, year = {2019}, author = {Parameswaran, R and Koehler, K and Rotenberg, MY and Burke, MJ and Kim, J and Jeong, KY and Hissa, B and Paul, MD and Moreno, K and Sarma, N and Hayes, T and Sudzilovsky, E and Park, HG and Tian, B}, title = {Optical stimulation of cardiac cells with a polymer-supported silicon nanowire matrix.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {413-421}, doi = {10.1073/pnas.1816428115}, pmid = {30538202}, issn = {1091-6490}, abstract = {Electronic pacemakers can treat electrical conduction disorders in hearts; however, they are invasive, bulky, and linked to increased incidence of infection at the tissue-device interface. Thus, researchers have looked to other more biocompatible methods for cardiac pacing or resynchronization, such as femtosecond infrared light pulsing, optogenetics, and polymer-based cardiac patches integrated with metal electrodes. Here we develop a biocompatible nongenetic approach for the optical modulation of cardiac cells and tissues. We demonstrate that a polymer-silicon nanowire composite mesh can be used to convert fast moving, low-radiance optical inputs into stimulatory signals in target cardiac cells. Our method allows for the stimulation of the cultured cardiomyocytes or ex vivo heart to beat at a higher target frequency.}, } @article {pmid30538201, year = {2018}, author = {Zhang, K and Shang, G and Padavannil, A and Wang, J and Sakthivel, R and Chen, X and Kim, M and Thompson, MG and García-Sastre, A and Lynch, KW and Chen, ZJ and Chook, YM and Fontoura, BMA}, title = {Structural-functional interactions of NS1-BP protein with the splicing and mRNA export machineries for viral and host gene expression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12218-E12227}, doi = {10.1073/pnas.1818012115}, pmid = {30538201}, issn = {1091-6490}, support = {R01 AI125524/AI/NIAID NIH HHS/United States ; }, abstract = {The influenza virulence factor NS1 protein interacts with the cellular NS1-BP protein to promote splicing and nuclear export of the viral M mRNAs. The viral M1 mRNA encodes the M1 matrix protein and is alternatively spliced into the M2 mRNA, which is translated into the M2 ion channel. These proteins have key functions in viral trafficking and budding. To uncover the NS1-BP structural and functional activities in splicing and nuclear export, we performed proteomics analysis of nuclear NS1-BP binding partners and showed its interaction with constituents of the splicing and mRNA export machineries. NS1-BP BTB domains form dimers in the crystal. Full-length NS1-BP is a dimer in solution and forms at least a dimer in cells. Mutations suggest that dimerization is important for splicing. The central BACK domain of NS1-BP interacts directly with splicing factors such as hnRNP K and PTBP1 and with the viral NS1 protein. The BACK domain is also the site for interactions with mRNA export factor Aly/REF and is required for viral M mRNA nuclear export. The crystal structure of the C-terminal Kelch domain shows that it forms a β-propeller fold, which is required for the splicing function of NS1-BP. This domain interacts with the polymerase II C-terminal domain and SART1, which are involved in recruitment of splicing factors and spliceosome assembly, respectively. NS1-BP functions are not only critical for processing a subset of viral mRNAs but also impact levels and nuclear export of a subset of cellular mRNAs encoding factors involved in metastasis and immunity.}, } @article {pmid30538200, year = {2018}, author = {Striessnig, J}, title = {Getting a handle on CaV2.2 (N-type) voltage-gated Ca2+ channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12848-12850}, doi = {10.1073/pnas.1818608115}, pmid = {30538200}, issn = {1091-6490}, mesh = {*Calcium Channels, N-Type ; *Protein Subunits ; }, } @article {pmid30538199, year = {2018}, author = {Dumitrache, LC and Shimada, M and Downing, SM and Kwak, YD and Li, Y and Illuzzi, JL and Russell, HR and Wilson, DM and McKinnon, PJ}, title = {Apurinic endonuclease-1 preserves neural genome integrity to maintain homeostasis and thermoregulation and prevent brain tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12285-E12294}, doi = {10.1073/pnas.1809682115}, pmid = {30538199}, issn = {1091-6490}, abstract = {Frequent oxidative modification of the neural genome is a by-product of the high oxygen consumption of the nervous system. Rapid correction of oxidative DNA lesions is essential, as genome stability is a paramount determinant of neural homeostasis. Apurinic/apyrimidinic endonuclease 1 (APE1; also known as "APEX1" or "REF1") is a key enzyme for the repair of oxidative DNA damage, although the specific role(s) for this enzyme in the development and maintenance of the nervous system is largely unknown. Here, using conditional inactivation of murine Ape1, we identify critical roles for this protein in the brain selectively after birth, coinciding with tissue oxygenation shifting from a placental supply to respiration. While mice lacking APE1 throughout neurogenesis were viable with little discernible phenotype at birth, rapid and pronounced brain-wide degenerative changes associated with DNA damage were observed immediately after birth leading to early death. Unexpectedly, Ape1Nes-cre mice appeared hypothermic with persistent shivering associated with the loss of thermoregulatory serotonergic neurons. We found that APE1 is critical for the selective regulation of Fos1-induced hippocampal immediate early gene expression. Finally, loss of APE1 in combination with p53 inactivation resulted in a profound susceptibility to brain tumors, including medulloblastoma and glioblastoma, implicating oxidative DNA lesions as an etiologic agent in these diseases. Our study reveals APE1 as a major suppressor of deleterious oxidative DNA damage and uncovers specific and broad pathogenic consequences of respiratory oxygenation in the postnatal nervous system.}, } @article {pmid30538198, year = {2018}, author = {Dzombak, DA}, title = {Moving beyond forensic monitoring to understand and manage impacts of hydraulic fracturing for oil and gas development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13145-13147}, doi = {10.1073/pnas.1819171116}, pmid = {30538198}, issn = {1091-6490}, } @article {pmid30538197, year = {2018}, author = {Arieli, I and Babichenko, Y and Smorodinsky, R}, title = {Robust forecast aggregation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12135-E12143}, doi = {10.1073/pnas.1813934115}, pmid = {30538197}, issn = {1091-6490}, abstract = {Bayesian experts who are exposed to different evidence often make contradictory probabilistic forecasts. An aggregator, ignorant of the underlying model, uses this to calculate his or her own forecast. We use the notions of scoring rules and regret to propose a natural way to evaluate an aggregation scheme. We focus on a binary state space and construct low regret aggregation schemes whenever there are only two experts that either are Blackwell-ordered or receive conditionally independent and identically distributed (i.i.d.) signals. In contrast, if there are many experts with conditionally i.i.d. signals, then no scheme performs (asymptotically) better than a [Formula: see text] forecast.}, } @article {pmid30538196, year = {2018}, author = {Fichou, Y and Lin, Y and Rauch, JN and Vigers, M and Zeng, Z and Srivastava, M and Keller, TJ and Freed, JH and Kosik, KS and Han, S}, title = {Cofactors are essential constituents of stable and seeding-active tau fibrils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13234-13239}, doi = {10.1073/pnas.1810058115}, pmid = {30538196}, issn = {1091-6490}, support = {P41 GM103521/GM/NIGMS NIH HHS/United States ; R01 AG056058/AG/NIA NIH HHS/United States ; }, abstract = {Amyloid fibrils are cross-β-rich aggregates that are exceptionally stable forms of protein assembly. Accumulation of tau amyloid fibrils is involved in many neurodegenerative diseases, including Alzheimer's disease (AD). Heparin-induced aggregates have been widely used and assumed to be a good tau amyloid fibril model for most biophysical studies. Here we show that mature fibrils made of 4R tau variants, prepared with heparin or RNA, spontaneously depolymerize and release monomers when their cofactors are removed. We demonstrate that the cross-β-sheet assembly formed in vitro with polyanion addition is unstable at room temperature. We furthermore demonstrate high seeding capacity with transgenic AD mouse brain-extracted tau fibrils in vitro that, however, is exhausted after one generation, while supplementation with RNA cofactors resulted in sustained seeding over multiple generations. We suggest that tau fibrils formed in brains are supported by unknown cofactors and inhere higher-quality packing, as reflected in a more distinct conformational arrangement in the mouse fibril-seeded, compared with heparin-induced, tau fibrils. Our study suggests that the role of cofactors in tauopathies is a worthy focus of future studies, as they may be viable targets for diagnosis and therapeutics.}, } @article {pmid30538195, year = {2018}, author = {Gupta, SK and Luo, L and Yen, L}, title = {RNA-mediated gene fusion in mammalian cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12295-E12304}, doi = {10.1073/pnas.1814704115}, pmid = {30538195}, issn = {1091-6490}, abstract = {One of the hallmarks of cancer is the formation of oncogenic fusion genes as a result of chromosomal translocations. Fusion genes are presumed to form before fusion RNA expression. However, studies have reported the presence of fusion RNAs in individuals who were negative for chromosomal translocations. These observations give rise to "the cart before the horse" hypothesis, in which the genesis of a fusion RNA precedes the fusion gene. The fusion RNA then guides the genomic rearrangements that ultimately result in a gene fusion. However, RNA-mediated genomic rearrangements in mammalian cells have never been demonstrated. Here we provide evidence that expression of a chimeric RNA drives formation of a specified gene fusion via genomic rearrangement in mammalian cells. The process is: (i) specified by the sequence of chimeric RNA involved, (ii) facilitated by physiological hormone levels, (iii) permissible regardless of intrachromosomal (TMPRSS2-ERG) or interchromosomal (TMPRSS2-ETV1) fusion, and (iv) can occur in normal cells before malignant transformation. We demonstrate that, contrary to "the cart before the horse" model, it is the antisense rather than sense chimeric RNAs that effectively drive gene fusion, and that this disparity can be explained by transcriptional conflict. Furthermore, we identified an endogenous RNA AZI1 that functions as the "initiator" RNA to induce TMPRSS2-ERG fusion. RNA-driven gene fusion demonstrated in this report provides important insight in early disease mechanisms, and could have fundamental implications in the biology of mammalian genome stability, as well as gene-editing technology via mechanisms native to mammalian cells.}, } @article {pmid30538194, year = {2018}, author = {Lea, AJ and Akinyi, MY and Nyakundi, R and Mareri, P and Nyundo, F and Kariuki, T and Alberts, SC and Archie, EA and Tung, J}, title = {Dominance rank-associated gene expression is widespread, sex-specific, and a precursor to high social status in wild male baboons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12163-E12171}, doi = {10.1073/pnas.1811967115}, pmid = {30538194}, issn = {1091-6490}, support = {R01 HD088558/HD/NICHD NIH HHS/United States ; }, abstract = {In humans and other hierarchical species, social status is tightly linked to variation in health and fitness-related traits. Experimental manipulations of social status in female rhesus macaques suggest that this relationship is partially explained by status effects on immune gene regulation. However, social hierarchies are established and maintained in different ways across species: While some are based on kin-directed nepotism, others emerge from direct physical competition. We investigated how this variation influences the relationship between social status and immune gene regulation in wild baboons, where hierarchies in males are based on fighting ability but female hierarchies are nepotistic. We measured rank-related variation in gene expression levels in adult baboons of both sexes at baseline and in response to ex vivo stimulation with the bacterial endotoxin lipopolysaccharide (LPS). We identified >2,000 rank-associated genes in males, an order of magnitude more than in females. In males, high status predicted increased expression of genes involved in innate immunity and preferential activation of the NF-κB-mediated proinflammatory pathway, a pattern previously associated with low status in female rhesus macaques. Using Mendelian randomization, we reconcile these observations by demonstrating that high status-associated gene expression patterns are precursors, not consequences, of high social status in males, in support of the idea that physiological condition determines who attains high rank. Together, our work provides a test of the relationship between social status and immune gene regulation in wild primates. It also emphasizes the importance of social context in shaping the relationship between social status and immune function.}, } @article {pmid30538193, year = {2018}, author = {Zahednasab, H and Keyvani, H and Karampour, S and Harirchian, MH}, title = {Role of HHV-6 subtypes in accelerating EAE progression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12126}, doi = {10.1073/pnas.1817967115}, pmid = {30538193}, issn = {1091-6490}, } @article {pmid30538192, year = {2018}, author = {Leibovitch, EC and Jacobson, S}, title = {Reply to Zahednasab et al.: HHV-6 and marmoset EAE.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12127}, doi = {10.1073/pnas.1818755115}, pmid = {30538192}, issn = {1091-6490}, } @article {pmid30538164, year = {2019}, author = {Neal, CA and Brantley, SR and Antolik, L and Babb, JL and Burgess, M and Calles, K and Cappos, M and Chang, JC and Conway, S and Desmither, L and Dotray, P and Elias, T and Fukunaga, P and Fuke, S and Johanson, IA and Kamibayashi, K and Kauahikaua, J and Lee, RL and Pekalib, S and Miklius, A and Million, W and Moniz, CJ and Nadeau, PA and Okubo, P and Parcheta, C and Patrick, MR and Shiro, B and Swanson, DA and Tollett, W and Trusdell, F and Younger, EF and Zoeller, MH and Montgomery-Brown, EK and Anderson, KR and Poland, MP and Ball, JL and Bard, J and Coombs, M and Dietterich, HR and Kern, C and Thelen, WA and Cervelli, PF and Orr, T and Houghton, BF and Gansecki, C and Hazlett, R and Lundgren, P and Diefenbach, AK and Lerner, AH and Waite, G and Kelly, P and Clor, L and Werner, C and Mulliken, K and Fisher, G and Damby, D}, title = {The 2018 rift eruption and summit collapse of Kīlauea Volcano.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6425}, pages = {367-374}, doi = {10.1126/science.aav7046}, pmid = {30538164}, issn = {1095-9203}, abstract = {In 2018, Kīlauea Volcano experienced its largest lower East Rift Zone (LERZ) eruption and caldera collapse in at least 200 years. After collapse of the Pu'u 'Ō'ō vent on 30 April, magma propagated downrift. Eruptive fissures opened in the LERZ on 3 May, eventually extending ~6.8 kilometers. A 4 May earthquake [moment magnitude (Mw) 6.9] produced ~5 meters of fault slip. Lava erupted at rates exceeding 100 cubic meters per second, eventually covering 35.5 square kilometers. The summit magma system partially drained, producing minor explosions and near-daily collapses releasing energy equivalent to Mw 4.7 to 5.4 earthquakes. Activity declined rapidly on 4 August. Summit collapse and lava flow volume estimates are roughly equivalent-about 0.8 cubic kilometers. Careful historical observation and monitoring of Kīlauea enabled successful forecasting of hazardous events.}, } @article {pmid30537993, year = {2018}, author = {Kristof, K and Büttner, B and Grimm, A and Mewes, C and Schmack, B and Popov, AF and Ghadimi, M and Beissbarth, T and Hinz, J and Bergmann, I and Mansur, A}, title = {Anaemia requiring red blood cell transfusion is associated with unfavourable 90-day survival in surgical patients with sepsis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {879}, doi = {10.1186/s13104-018-3988-z}, pmid = {30537993}, issn = {1756-0500}, support = {ZN3168//Volkswagen Foundation/ ; }, abstract = {OBJECTIVE: The mortality associated with sepsis remains unacceptably high, despite modern high-quality intensive care. Based on the results from previous studies, anaemia and its management in patients with sepsis appear to impact outcomes; however, the transfusion policy is still being debated, and the ideal approach may be extremely specific to the individual. This study aimed to investigate the long-term impact of anaemia requiring red blood cell (RBC) transfusion on mortality and disease severity in patients with sepsis. We studied a general surgical intensive care unit (ICU) population, excluding cardiac surgery patients. 435 patients were enrolled in this observational study between 2012 and 2016.

RESULTS: Patients who received RBC transfusion between 28 days before and 28 days after the development of sepsis (n = 302) exhibited a significantly higher 90-day mortality rate (34.1% vs 19.6%; P = 0.004, Kaplan-Meier analysis). This association remained significant after adjusting for confounders in the multivariate Cox regression analysis (hazard ratio 1.68; 95% confidence interval 1.03-2.73; P = 0.035). Patients who received transfusions also showed significantly higher morbidity scores, such as SOFA scores, and ICU lengths of stay compared to patients without transfusions (n = 133). Our results indicate that anaemia and RBC transfusion are associated with unfavourable outcomes in patients with sepsis.}, } @article {pmid30537981, year = {2018}, author = {Krajaejun, T and Kittichotirat, W and Patumcharoenpol, P and Rujirawat, T and Lohnoo, T and Yingyong, W}, title = {Data on whole genome sequencing of the oomycete Pythium insidiosum strain CBS 101555 from a horse with pythiosis in Brazil.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {880}, doi = {10.1186/s13104-018-3968-3}, pmid = {30537981}, issn = {1756-0500}, support = {BRG5980009//Thailand Research Fund/ ; KMUTT 55th Anniversary Commemorative Fund//King Mongkut's University of Technology Thonburi/ ; CF_60001//Faculty of Medicine, Ramathibodi Hospital, Mahidol University/ ; CF_61007//Faculty of Medicine, Ramathibodi Hospital, Mahidol University/ ; }, abstract = {OBJECTIVES: The oomycete Pythium insidiosum infects humans and animals worldwide, and causes the life-threatening condition, called pythosis. Most patients lose infected organs or die from the disease. Comparative genomic analyses of different P. insidiosum strains could provide new insights into its pathobiology, and can lead to discovery of an effective treatment method. Several draft genomes of P. insidiosum are publicly available: three from Asia (Thailand), and one each from North (the United States) and Central (Costa Rica) Americas. We report another draft genome of P. insidiosum isolated from South America (Brazil), to serve as a resource for comprehensive genomic studies.

DATA DESCRIPTION: In this study, we report genome sequence of the P. insidiosum strain CBS 101555, isolated from a horse with pythiosis in Brazil. One paired-end (180-bp insert) library of processed genomic DNA was prepared for Illumina HiSeq 2500-based sequencing. Assembly of raw reads provided genome size of 48.9 Mb, comprising 60,602 contigs. A total of 23,254 genes were predicted and classified into 18,305 homologous gene clusters. Compared with the reference genome (the P. insidiosum strain Pi-S), 1,475,337 sequence variants (SNPs and INDELs) were identified in the organism. The genome sequence data has been deposited in DDBJ under the accession numbers BCFP01000001-BCFP01060602.}, } @article {pmid30537949, year = {2018}, author = {Norris, ET and Wang, L and Conley, AB and Rishishwar, L and Mariño-Ramírez, L and Valderrama-Aguirre, A and Jordan, IK}, title = {Genetic ancestry, admixture and health determinants in Latin America.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 8}, pages = {861}, pmid = {30537949}, issn = {1471-2164}, support = {ZIA LM082713/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Modern Latin American populations were formed via genetic admixture among ancestral source populations from Africa, the Americas and Europe. We are interested in studying how combinations of genetic ancestry in admixed Latin American populations may impact genomic determinants of health and disease. For this study, we characterized the impact of ancestry and admixture on genetic variants that underlie health- and disease-related phenotypes in population genomic samples from Colombia, Mexico, Peru, and Puerto Rico.

RESULTS: We analyzed a total of 347 admixed Latin American genomes along with 1102 putative ancestral source genomes from Africans, Europeans, and Native Americans. We characterized the genetic ancestry, relatedness, and admixture patterns for each of the admixed Latin American genomes, finding a spectrum of ancestry proportions within and between populations. We then identified single nucleotide polymorphisms (SNPs) with anomalous ancestry-enrichment patterns, i.e. SNPs that exist in any given Latin American population at a higher frequency than expected based on the population's genetic ancestry profile. For this set of ancestry-enriched SNPs, we inspected their phenotypic impact on disease, metabolism, and the immune system. All four of the Latin American populations show ancestry-enrichment for a number of shared pathways, yielding evidence of similar selection pressures on these populations during their evolution. For example, all four populations show ancestry-enriched SNPs in multiple genes from immune system pathways, such as the cytokine receptor interaction, T cell receptor signaling, and antigen presentation pathways. We also found SNPs with excess African or European ancestry that are associated with ancestry-specific gene expression patterns and play crucial roles in the immune system and infectious disease responses. Genes from both the innate and adaptive immune system were found to be regulated by ancestry-enriched SNPs with population-specific regulatory effects.

CONCLUSIONS: Ancestry-enriched SNPs in Latin American populations have a substantial effect on health- and disease-related phenotypes. The concordant impact observed for same phenotypes across populations points to a process of adaptive introgression, whereby ancestry-enriched SNPs with specific functional utility appear to have been retained in modern populations by virtue of their effects on health and fitness.}, } @article {pmid30537948, year = {2018}, author = {Karmakar, K and Nath, U and Nataraja, KN and Chakravortty, D}, title = {Root mediated uptake of Salmonella is different from phyto-pathogen and associated with the colonization of edible organs.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {344}, doi = {10.1186/s12870-018-1578-9}, pmid = {30537948}, issn = {1471-2229}, support = {DAE00195//Department of Atomic Energy, Government of India/ ; }, mesh = {*Food Contamination ; Plant Diseases/microbiology ; Plant Roots/*microbiology ; Salinity ; Salmonella/*metabolism ; }, abstract = {BACKGROUND: Pre-harvest contamination of fruits and vegetables by Salmonella in fields is one of the causes of food-borne outbreaks. Natural openings like stomata, hydathodes and fruit cracks are known to serve as entry points. While there are reports indicating that Salmonella colonize and enter root through lateral root emerging area, further investigations regarding how the accessibility of Salmonella to lateral root is different from phyto-pathogenic bacteria, the efficacy of lateral root to facilitate entry have remained unexplored. In this study we attempted to investigate the lateral root mediated entry of Salmonella, and to bridge this gap in knowledge.

RESULTS: Unlike phytopathogens, Salmonella cannot utilize cellulose as the sole carbon source. This negates the fact of active entry by degrading plant cellulose and pectin. Endophytic Salmonella colonization showed a high correlation with number of lateral roots. When given equal opportunity to colonize the plants with high or low lateral roots, Salmonella internalization was found higher in the plants with more lateral roots. However, the epiphytic colonization in both these plants remained unaltered. To understand the ecological significance, we induced lateral root production by increasing soil salinity which made the plants susceptible to Salmonella invasion and the plants showed higher Salmonella burden in the aerial organs.

CONCLUSION: Salmonella, being unable to degrade plant cell wall material relies heavily on natural openings. Therefore, its invasion is highly dependent on the number of lateral roots which provides an entry point because of the epidermis remodeling. Thus, when number of lateral root was enhanced by increasing the soil salinity, plants became susceptible to Salmonella invasion in roots and its transmission to aerial organs.}, } @article {pmid30537933, year = {2018}, author = {Tobar-Tosse, F and Veléz, PE and Ocampo-Toro, E and Moreno, PA}, title = {Structure, clustering and functional insights of repeats configurations in the upstream promoter region of the human coding genes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 8}, pages = {862}, pmid = {30537933}, issn = {1471-2164}, abstract = {BACKGROUND: Repetitive DNA sequences (Repeats) are significant regions in the human genome that have a specific genomic distribution, structure, and several binding sites for genome architecture and function. In consequence, the possible configurations of Repeats in specific and dynamic regions like the gene promoters could define footprints for molecular mechanisms, pathways, and cell function beyond their density in the genome. Here we explored the distribution of Repeats in the upstream promoter region of the human coding genes with the aim to identify specific configurations, clusters and functional meaning of those elements. Our method includes structural descriptions, hierarchical clustering, pathway association, and functional enrichment analysis.

RESULTS: We report here several configurations of Repeats in the upstream promoter region (UPR), which define 2729 patterns for the 80% of the human coding genes. There are 47 types of Repeats in these configurations, where the most frequent were Alu, Low_complexity, MIR, Simple_repeat, LINE/L2, LINE/L1, hAT-Charlie, and ERV1. The distribution, length, and the high frequency of Repeats in the UPR defines several patterns and clusters, where the minimum frequency of configuration among Repeats was higher than 0.7. We found those clusters associated with cellular pathways and ontologies; thus, it was plausible to determine groups of Repeats to specific functional insights, for example, pathways for Genetic Information Processing or Metabolism shows particular groups of Repeats with specific configurations.

CONCLUSION: Based on these findings, we propose that specific configurations of repetitive elements describe frequent patterns in the upstream promoter for sets of human coding genes, which those correlated to specific and essential cell pathways and functions.}, } @article {pmid30537932, year = {2018}, author = {Vailati-Riboni, M and Bucktrout, RE and Zhan, S and Geiger, A and McCann, JC and Akers, RM and Loor, JJ}, title = {Higher plane of nutrition pre-weaning enhances Holstein calf mammary gland development through alterations in the parenchyma and fat pad transcriptome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {900}, doi = {10.1186/s12864-018-5303-8}, pmid = {30537932}, issn = {1471-2164}, support = {2016-67015-24565//Agricultural Research Service/ ; 2016-67011-24703//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: To reduce costs of rearing replacement heifers, researchers have focused on decreasing age at breeding and first calving. To increase returns upon initiation of lactation the focus has been on increasing mammary development prior to onset of first lactation. Enhanced plane of nutrition pre-weaning may benefit the entire replacement heifer operation by promoting mammary gland development and greater future production.

METHODS: Twelve Holstein heifer calves (< 1 week old) were reared on 1 of 2 dietary treatments (n = 6/group) for 8 weeks: a control group fed a restricted milk replacer at 0.45 kg/d (R, 20% crude protein, 20% fat), or an accelerated group fed an enhanced milk replacer at 1.13 kg/d (EH, 28% crude protein, 25% fat). At weaning (8 weeks), calves were euthanized and sub-samples of mammary parenchyma (PAR) and mammary fat pad (MFP) were harvested upon removal from the body. Total RNA from both tissues was extracted and sequenced using the Illumina HiSeq2500 platform. The Dynamic Impact Approach (DIA) and Ingenuity Pathway Analysis (IPA) were used for pathway analysis and functions, gene networks, and cross-talk analyses of the two tissues.

RESULTS: When comparing EH vs R 1561 genes (895 upregulated, 666 downregulated) and 970 genes (506 upregulated, 464 downregulated) were differentially expressed in PAR and MFP, respectively. DIA and IPA results highlight a greater proliferation and differentiation activity in both PAR and MFP, supported by an increased metabolic activity. When calves were fed EH, the PAR displayed transcriptional signs of greater overall organ development, with higher ductal growth and branching, together with a supportive blood vessel and nerve network. These activities were mediated by intracellular cascades, such as AKT, SHH, MAPK, and Wnt, probably activated by hormones, growth factors, and endogenous molecules. The analysis also revealed strong communication between MFP and PAR.

CONCLUSION: The transcriptomics and bioinformatics approach highlighted key mechanisms that mediate the mammary gland response to a higher plane of nutrition in the pre-weaning period.}, } @article {pmid30537931, year = {2018}, author = {Benavides, A and Isaza, JP and Niño-García, JP and Alzate, JF and Cabarcas, F}, title = {CLAME: a new alignment-based binning algorithm allows the genomic description of a novel Xanthomonadaceae from the Colombian Andes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 8}, pages = {858}, pmid = {30537931}, issn = {1471-2164}, abstract = {BACKGROUND: Hot spring bacteria have unique biological adaptations to survive the extreme conditions of these environments; these bacteria produce thermostable enzymes that can be used in biotechnological and industrial applications. However, sequencing these bacteria is complex, since it is not possible to culture them. As an alternative, genome shotgun sequencing of whole microbial communities can be used. The problem is that the classification of sequences within a metagenomic dataset is very challenging particularly when they include unknown microorganisms since they lack genomic reference. We failed to recover a bacterium genome from a hot spring metagenome using the available software tools, so we develop a new tool that allowed us to recover most of this genome.

RESULTS: We present a proteobacteria draft genome reconstructed from a Colombian's Andes hot spring metagenome. The genome seems to be from a new lineage within the family Rhodanobacteraceae of the class Gammaproteobacteria, closely related to the genus Dokdonella. We were able to generate this genome thanks to CLAME. CLAME, from Spanish "CLAsificador MEtagenomico", is a tool to group reads in bins. We show that most reads from each bin belong to a single chromosome. CLAME is very effective recovering most of the reads belonging to the predominant species within a metagenome.

CONCLUSIONS: We developed a tool that can be used to extract genomes (or parts of them) from a complex metagenome.}, } @article {pmid30537930, year = {2018}, author = {Kirsch, R and Seemann, SE and Ruzzo, WL and Cohen, SM and Stadler, PF and Gorodkin, J}, title = {Identification and characterization of novel conserved RNA structures in Drosophila.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {899}, pmid = {30537930}, issn = {1471-2164}, support = {0603-00320B//Innovation Fund Denmark/ ; DFG SPP 1258 grant no. STA 850/10-2//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Comparative genomics approaches have facilitated the discovery of many novel non-coding and structured RNAs (ncRNAs). The increasing availability of related genomes now makes it possible to systematically search for compensatory base changes - and thus for conserved secondary structures - even in genomic regions that are poorly alignable in the primary sequence. The wealth of available transcriptome data can add valuable insight into expression and possible function for new ncRNA candidates. Earlier work identifying ncRNAs in Drosophila melanogaster made use of sequence-based alignments and employed a sliding window approach, inevitably biasing identification toward RNAs encoded in the more conserved parts of the genome.

RESULTS: To search for conserved RNA structures (CRSs) that may not be highly conserved in sequence and to assess the expression of CRSs, we conducted a genome-wide structural alignment screen of 27 insect genomes including D. melanogaster and integrated this with an extensive set of tiling array data. The structural alignment screen revealed ∼30,000 novel candidate CRSs at an estimated false discovery rate of less than 10%. With more than one quarter of all individual CRS motifs showing sequence identities below 60%, the predicted CRSs largely complement the findings of sliding window approaches applied previously. While a sixth of the CRSs were ubiquitously expressed, we found that most were expressed in specific developmental stages or cell lines. Notably, most statistically significant enrichment of CRSs were observed in pupae, mainly in exons of untranslated regions, promotors, enhancers, and long ncRNAs. Interestingly, cell lines were found to express a different set of CRSs than were found in vivo. Only a small fraction of intergenic CRSs were co-expressed with the adjacent protein coding genes, which suggests that most intergenic CRSs are independent genetic units.

CONCLUSIONS: This study provides a more comprehensive view of the ncRNA transcriptome in fly as well as evidence for differential expression of CRSs during development and in cell lines.}, } @article {pmid30537929, year = {2018}, author = {Barski, M}, title = {BASILIScan: a tool for high-throughput analysis of intrinsic disorder patterns in homologous proteins.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {902}, doi = {10.1186/s12864-018-5322-5}, pmid = {30537929}, issn = {1471-2164}, abstract = {BACKGROUND: Intrinsic structural disorder is a common property of many proteins, especially in eukaryotic and virus proteomes. The tendency of some proteins or protein regions to exist in a disordered state usually precludes their structural characterisation and renders them especially difficult for experimental handling after recombinant expression.

RESULTS: A new intuitive, publicly-available computational resource, called BASILIScan, is presented here. It provides a BLAST-based search for close homologues of the protein of interest, integrated with a simultaneous prediction of intrinsic disorder together with a robust data viewer and interpreter. This allows for a quick, high-throughput screening, scoring and selection of closely-related yet highly structured homologues of the protein of interest. Comparative parallel analysis of the conservation of extended regions of disorder in multiple sequences is also offered. The use of BASILIScan and its capacity for yielding biologically applicable predictions is demonstrated. Using a high-throughput BASILIScan screen it is also shown that a large proportion of the human proteome displays homologous sequences of superior intrinsic structural order in many related species.

CONCLUSION: Through the swift identification of intrinsically stable homologues and poorly conserved disordered regions by the BASILIScan software, the chances of successful recombinant protein expression and compatibility with downstream applications such as crystallisation can be greatly increased.}, } @article {pmid30537928, year = {2018}, author = {Cai, Z and Guldbrandtsen, B and Lund, MS and Sahana, G}, title = {Retraction Note: Dissecting closely linked association signals in combination with the mammalian phenotype database can identify candidate genes in dairy cattle.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {111}, pmid = {30537928}, issn = {1471-2156}, abstract = {ᅟ.}, } @article {pmid30537927, year = {2018}, author = {Martinez-Romero, J and Bueno-Fortes, S and Martín-Merino, M and Ramirez de Molina, A and De Las Rivas, J}, title = {Survival marker genes of colorectal cancer derived from consistent transcriptomic profiling.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 8}, pages = {857}, pmid = {30537927}, issn = {1471-2164}, abstract = {BACKGROUND: Identification of biomarkers associated with the prognosis of different cancer subtypes is critical to achieve better therapeutic assistance. In colorectal cancer (CRC) the discovery of stable and consistent survival markers remains a challenge due to the high heterogeneity of this class of tumors. In this work, we identified a new set of gene markers for CRC associated to prognosis and risk using a large unified cohort of patients with transcriptomic profiles and survival information.

RESULTS: We built an integrated dataset with 1273 human colorectal samples, which provides a homogeneous robust framework to analyse genome-wide expression and survival data. Using this dataset we identified two sets of genes that are candidate prognostic markers for CRC in stages III and IV, showing either up-regulation correlated with poor prognosis or up-regulation correlated with good prognosis. The top 10 up-regulated genes found as survival markers of poor prognosis (i.e. low survival) were: DCBLD2, PTPN14, LAMP5, TM4SF1, NPR3, LEMD1, LCA5, CSGALNACT2, SLC2A3 and GADD45B. The stability and robustness of the gene survival markers was assessed by cross-validation, and the best-ranked genes were also validated with two external independent cohorts: one of microarrays with 482 samples; another of RNA-seq with 269 samples. Up-regulation of the top genes was also proved in a comparison with normal colorectal tissue samples. Finally, the set of top 100 genes that showed overexpression correlated with low survival was used to build a CRC risk predictor applying a multivariate Cox proportional hazards regression analysis. This risk predictor yielded an optimal separation of the individual patients of the cohort according to their survival, with a p-value of 8.25e-14 and Hazard Ratio 2.14 (95% CI: 1.75-2.61).

CONCLUSIONS: The results presented in this work provide a solid rationale for the prognostic utility of a new set of genes in CRC, demonstrating their potential to predict colorectal tumor progression and evolution towards poor survival stages. Our study does not provide a fixed gene signature for prognosis and risk prediction, but instead proposes a robust set of genes ranked according to their predictive power that can be selected for additional tests with other CRC clinical cohorts.}, } @article {pmid30537926, year = {2018}, author = {Brunetti, SC and Arseneault, MKM and Gulick, PJ}, title = {Characterization of the Esi3/RCI2/PMP3 gene family in the Triticeae.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {898}, pmid = {30537926}, issn = {1471-2164}, abstract = {BACKGROUND: Members of the Early Salt Induced 3 (Esi3/RCI2/PMP3) gene family in plants have been shown to be induced in response to both biotic and abiotic stresses and to enhance stress tolerance in both transgenic plants and Saccharomyces cerevisiae. Esi3 was first identified as a salt stress induced gene in the salt tolerant wild wheat grass, Lophopyrum elongatum, and subsequently homologous genes in many other species were found to be members of the gene family. These include Arabidopsis thaliana and Oryza sativa where they are referred to as Rare Cold Inducible 2 (RCI2), and Zea mays where they are referred to as Plasma Membrane Protein 3 (PMP3). This study characterizes the Esi3 family members in Triticum aestivum and explores the tissue specific expression patterns of the gene family members as well as their response to a variety of environmental stresses.

RESULTS: The Esi3 gene family was found to have a total of 29 family members comprised of ten paralogous groups in the hexaploid T. aestivum. Each paralogous group contains three homeologous copies, one in each of the A, B and D genomes with the exception of Esi3-2 which is missing the B copy. The genes of the Esi3 gene family were also identified in four other monocot species, Aegilops tauschii, Hordeum vulgare, Secale cereale and Sorghum bicolor, and were confirmed or corrected for Brachypodium distachyon, Oryza sativa and Zea mays, as well as the dicot Arabidopsis thaliana. Gene expression of the Esi3s was analyzed using tissue-specific, abiotic and biotic stress RNA-Seq 454 sequence libraries and Affymetrix microarray data for T. aestivum.

CONCLUSIONS: Members of nearly all paralogous groups of the Esi3 genes in T. aestivum have altered gene expression in response to abiotic or biotic stress conditions. In addition, there are modest differences in gene expression among homeologous members of the gene family. This suggests that the Esi3 gene family plays an important role in the plants response to the stresses presented in this study. The Esi3-9 in T. aestivum has a unique N terminal extension placing it into Group III, a new group for the Esi3/RCI2/PMP3 gene family.}, } @article {pmid30537925, year = {2018}, author = {Arce, D and Spetale, F and Krsticevic, F and Cacchiarelli, P and Las Rivas, J and Ponce, S and Pratta, G and Tapia, E}, title = {Regulatory motifs found in the small heat shock protein (sHSP) gene family in tomato.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 8}, pages = {860}, pmid = {30537925}, issn = {1471-2164}, abstract = {BACKGROUND: In living organisms, small heat shock proteins (sHSPs) are triggered in response to stress situations. This family of proteins is large in plants and, in the case of tomato (Solanum lycopersicum), 33 genes have been identified, most of them related to heat stress response and to the ripening process. Transcriptomic and proteomic studies have revealed complex patterns of expression for these genes. In this work, we investigate the coregulation of these genes by performing a computational analysis of their promoter architecture to find regulatory motifs known as heat shock elements (HSEs). We leverage the presence of sHSP members that originated from tandem duplication events and analyze the promoter architecture diversity of the whole sHSP family, focusing on the identification of HSEs.

RESULTS: We performed a search for conserved genomic sequences in the promoter regions of the sHSPs of tomato, plus several other proteins (mainly HSPs) that are functionally related to heat stress situations or to ripening. Several computational analyses were performed to build multiple sequence motifs and identify transcription factor binding sites (TFBS) homologous to HSF1AE and HSF21 in Arabidopsis. We also investigated the expression and interaction of these proteins under two heat stress situations in whole tomato plants and in protoplast cells, both in the presence and in the absence of heat shock transcription factor A2 (HsfA2). The results of these analyses indicate that different sHSPs are up-regulated depending on the activation or repression of HsfA2, a key regulator of HSPs. Further, the analysis of protein-protein interaction between the sHSP protein family and other heat shock response proteins (Hsp70, Hsp90 and MBF1c) suggests that several sHSPs are mediating alternative stress response through a regulatory subnetwork that is not dependent on HsfA2.

CONCLUSIONS: Overall, this study identifies two regulatory motifs (HSF1AE and HSF21) associated with the sHSP family in tomato which are considered genomic HSEs. The study also suggests that, despite the apparent redundancy of these proteins, which has been linked to gene duplication, tomato sHSPs showed different up-regulation and different interaction patterns when analyzed under different stress situations.}, } @article {pmid30537924, year = {2018}, author = {Dong, Q and Shi, L and Li, Y and Jiang, M and Sun, H and Wang, B and Cheng, H and Zhang, Y and Shao, T and Shi, Y and Wang, Z}, title = {Differential responses of Lasiopodomys mandarinus and Lasiopodomys brandtii to chronic hypoxia: a cross-species brain transcriptome analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {901}, doi = {10.1186/s12864-018-5318-1}, pmid = {30537924}, issn = {1471-2164}, support = {31372193//National Natural Science Foundation of China (CN)/ ; }, abstract = {BACKGROUND: Subterranean rodents have evolved many features to adapt to their hypoxic environment. The brain is an organ that is particularly vulnerable to damage caused by exposure to hypoxic conditions. To investigate the mechanisms of adaption to a hypoxic underground environment, we carried out a cross-species brain transcriptome analysis by RNA sequencing and identified genes that are differentially expressed between the subterranean vole Lasiopodomys mandarinus and the closely related above-ground species Lasiopodomys brandtii under chronic hypoxia [10.0% oxygen (O2)] and normoxia (20.9% O2).

RESULTS: A total of 355 million clean reads were obtained, including 69,611 unigenes in L. mandarinus and 69,360 in L. brandtii. A total of 235 and 92 differentially expressed genes (DEGs) were identified by comparing the hypoxic and control groups of L. mandarinus and L. brandtii, respectively. A Gene Ontology (GO) analysis showed that upregulated DEGs in both species had similar functions in response to hypoxia, whereas downregulated DEGs in L. mandarinus were enriched GO terms related to enzymes involved in aerobic reactions. In the Kyoto Encyclopedia of Genes and Genomes pathway analysis, upregulated DEGs in L. mandarinus were associated with angiogenesis and the increased O2 transport capacity of red blood cells, whereas downregulated DEGs were associated with immune responses. On the other hand, upregulated DEGs in L. brandtii were associated with cell survival, vascular endothelial cell proliferation, and neuroprotection, while downregulated genes were related to the synaptic transmission by neurons.

CONCLUSIONS: L. mandarinus actively adapts its physiological functions to hypoxic conditions, for instance by increasing O2 transport capacity and modulating O2 consumption. In contrast, L. brandtii reacts passively to hypoxia by decreasing overall activity in order to reduce O2 consumption. These results provide insight into hypoxia adaptation mechanisms in subterranean rodents that may be applicable to humans living at high altitudes or operating in other O2-poor environments.}, } @article {pmid30537923, year = {2018}, author = {Botero, K and Restrepo, S and Pinzón, A}, title = {A genome-scale metabolic model of potato late blight suggests a photosynthesis suppression mechanism.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 8}, pages = {863}, pmid = {30537923}, issn = {1471-2164}, abstract = {BACKGROUND: Phytophthora infestans is a plant pathogen that causes an important plant disease known as late blight in potato plants (Solanum tuberosum) and several other solanaceous hosts. This disease is the main factor affecting potato crop production worldwide. In spite of the importance of the disease, the molecular mechanisms underlying the compatibility between the pathogen and its hosts are still unknown.

RESULTS: To explain the metabolic response of late blight, specifically photosynthesis inhibition in infected plants, we reconstructed a genome-scale metabolic network of the S. tuberosum leaf, PstM1. This metabolic network simulates the effect of this disease in the leaf metabolism. PstM1 accounts for 2751 genes, 1113 metabolic functions, 1773 gene-protein-reaction associations and 1938 metabolites involved in 2072 reactions. The optimization of the model for biomass synthesis maximization in three infection time points suggested a suppression of the photosynthetic capacity related to the decrease of metabolic flux in light reactions and carbon fixation reactions. In addition, a variation pattern in the flux of carboxylation to oxygenation reactions catalyzed by RuBisCO was also identified, likely to be associated to a defense response in the compatible interaction between P. infestans and S. tuberosum.

CONCLUSIONS: In this work, we introduced simultaneously the first metabolic network of S. tuberosum and the first genome-scale metabolic model of the compatible interaction of a plant with P. infestans.}, } @article {pmid30537922, year = {2018}, author = {Noreña-P, A and González Muñoz, A and Mosquera-Rendón, J and Botero, K and Cristancho, MA}, title = {Colombia, an unknown genetic diversity in the era of Big Data.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 8}, pages = {859}, pmid = {30537922}, issn = {1471-2164}, abstract = {BACKGROUND: Latin America harbors some of the most biodiverse countries in the world, including Colombia. Despite the increasing use of cutting-edge technologies in genomics and bioinformatics in several biological science fields around the world, the region has fallen behind in the inclusion of these approaches in biodiversity studies. In this study, we used data mining methods to search in four main public databases of genetic sequences such as: NCBI Nucleotide and BioProject, Pathosystems Resource Integration Center, and Barcode of Life Data Systems databases. We aimed to determine how much of the Colombian biodiversity is contained in genetic data stored in these public databases and how much of this information has been generated by national institutions. Additionally, we compared this data for Colombia with other countries of high biodiversity in Latin America, such as Brazil, Argentina, Costa Rica, Mexico, and Peru.

RESULTS: In Nucleotide, we found that 66.84% of total records for Colombia have been published at the national level, and this data represents less than 5% of the total number of species reported for the country. In BioProject, 70.46% of records were generated by national institutions and the great majority of them is represented by microorganisms. In BOLD Systems, 26% of records have been submitted by national institutions, representing 258 species for Colombia. This number of species reported for Colombia span approximately 0.46% of the total biodiversity reported for the country (56,343 species). Finally, in PATRIC database, 13.25% of the reported sequences were contributed by national institutions. Colombia has a better biodiversity representation in public databases in comparison to other Latin American countries, like Costa Rica and Peru. Mexico and Argentina have the highest representation of species at the national level, despite Brazil and Colombia, which actually hold the first and second places in biodiversity worldwide.

CONCLUSIONS: Our findings show gaps in the representation of the Colombian biodiversity at the molecular and genetic levels in widely consulted public databases. National funding for high-throughput molecular research, NGS technologies costs, and access to genetic resources are limiting factors. This fact should be taken as an opportunity to foster the development of collaborative projects between research groups in the Latin American region to study the vast biodiversity of these countries using 'omics' technologies.}, } @article {pmid30537487, year = {2019}, author = {Stracker, TH}, title = {E2F4/5-mediated transcriptional control of multiciliated cell differentiation: redundancy or fine-tuning?.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {20-21}, doi = {10.1016/j.ydbio.2018.12.007}, pmid = {30537487}, issn = {1095-564X}, } @article {pmid30537406, year = {2018}, author = {Singer, E and Bonnette, J and Kenaley, SC and Woyke, T and Juenger, TE}, title = {Plant compartment and genetic variation drive microbiome composition in switchgrass roots.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12727}, pmid = {30537406}, issn = {1758-2229}, support = {DE-SC0014156//U.S. DOE Office of Science Biological and Environmental Research/ ; DE-AC02-05CH11231//U.S. DOE Office of Science/ ; }, abstract = {Switchgrass (Panicum virgatum) is a promising biofuel crop native to the United States with genotypes that are adapted to a wide range of distinct ecosystems. Various plants have been shown to undergo symbioses with plant growth-promoting bacteria and fungi, however, plant-associated microbial communities of switchgrass have not been extensively studied to date. We present 16S ribosomal RNA gene and internal transcribed spacer (ITS) data of rhizosphere and root endosphere compartments of four switchgrass genotypes to test the hypothesis that host selection of its root microbiota prevails after transfer to non-native soil. We show that differences in bacterial, archaeal and fungal community composition and diversity are strongly driven by plant compartment and switchgrass genotypes and ecotypes. Plant-associated microbiota show an enrichment in Alphaproteobacteria and Actinobacteria as well as Sordariales and Pleosporales compared with the surrounding soil. Root associated compartments display low-complexity communities dominated and enriched in Actinobacteria, in particular Streptomyces, in the lowland genotypes, and in Alphaproteobacteria, specifically Sphingobium, in the upland genotypes. Our comprehensive root analysis serves as a snapshot of host-specific bacterial and fungal associations of switchgrass in the field and confirms that host-selected microbiomes persist after transfer to non-native soil.}, } @article {pmid30537399, year = {2018}, author = {Chang, C and Cai, E and Deng, YZ and Mei, D and Qiu, S and Chen, B and Zhang, LH and Jiang, Z}, title = {cAMP/PKA signalling pathway regulates redox homeostasis essential for Sporisorium scitamineum mating/filamentation and virulence.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14496}, pmid = {30537399}, issn = {1462-2920}, support = {No. 31672091//National Natural Science Foundation of China/ ; 31672091//National Natural Science Foundation of China/ ; 2015CB150600//National Natural Science Foundation of China/ ; No.2013S034//Innovative R&D Team Program of Guangdong Province, China/ ; 2013S034//Innovative R&D Team Program of Guangdong Province, China/ ; No 2015CB150600//National 973 Program of China/ ; }, abstract = {The fungal pathogen Sporisorium scitamineum causes sugarcane smut disease. The formation and growth of dikaryotic hypha after sexual mating is critical for S. scitamineum pathogenicity, however regulation of S. scitimineum mating has not been studied in detail. We identified and characterized the core components of the conserved cAMP/PKA pathway in S. scitamineum by reverse genetics. Our results showed that cAMP/PKA signalling pathway is essential for proper mating and filamentation, and thus critical for S. scitamineum virulence. We further demonstrated that an elevated intracellular ROS (reactive oxygen species) level promotes S. scitamineum mating-filamentation, via transcriptional regulation of ROS catabolic enzymes, and is under regulation of the cAMP/PKA signalling pathway. Furthermore, we found that fungal cAMP/PKA signalling pathway is also involved in regulation of host ROS response. Overall, our work displayed a positive role of elevated intracellular ROS in fungal differentiation and virulence.}, } @article {pmid30537211, year = {2018}, author = {Murray, EA and Burand, J and Trikoz, N and Schnabel, J and Grab, H and Danforth, BN}, title = {Viral transmission in honey bees and native bees, supported by a global black queen cell virus phylogeny.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14501}, pmid = {30537211}, issn = {1462-2920}, support = {2011-51181-30673//National Institute of Food and Agriculture/ ; }, abstract = {In recent decades, we have realized that honey bee viruses are not, in fact, exclusive to honey bees. The potential impact of Apis-affiliated viruses on native pollinators is prompting concern. Our research addresses the issue of virus crossover between honey bees and native bees foraging in the same localities. We measured the presence of black queen cell virus (BQCV), deformed wing virus (DWV) and sacbrood virus (SBV) in managed Apis mellifera (honey bees) and native Andrena spp. (subgenus Melandrena) bee populations in five commercial orchards. We identified viral presence across sites and bees and related these data to measures of bee community diversity. All viruses were found in both managed and native bees, and BQCV was the most common virus in each. To establish evidence for viral crossover between taxa, we undertook an additional examination of BQCV where 74 samples were sequenced and placed in a global phylogenic framework of hundreds of BQCV strains. We demonstrate pathogen sharing across managed honey bees and distantly related wild bees. This phylogenetic analysis contributes to growing evidence for host switching and places local incidence patterns in a worldwide context, revealing multispecies viral transmission.}, } @article {pmid30537045, year = {2018}, author = {Navalón, G and Bright, JA and Marugán-Lobón, J and Rayfield, EJ}, title = {The evolutionary relationship among beak shape, mechanical advantage, and feeding ecology in modern birds.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13655}, pmid = {30537045}, issn = {1558-5646}, support = {CGL-2013-42643//Spanish MINECO/ ; GELY NE1262//The Alumni Foundation, University of Bristol, UK/ ; BB/I011668/1//BBSRC/ ; }, abstract = {Extensive research on avian adaptive radiations has led to a presumption that beak morphology predicts feeding ecology in birds. However, this ecomorphological relationship has only been quantified in a handful of avian lineages, where associations are of variable strength, and never at a broad macroevolutionary scale. Here, we used shape analysis and phylogenetic comparative methods to quantify the relationships among beak shape, mechanical advantage, and two measures of feeding ecology (feeding behavior and semiquantitative dietary preferences) in a broad sample of modern birds, comprising most living orders. We found a complex relationship, with most variables showing a significant relationship with feeding ecology but little explanatory power. For example, diet accounts for less than 12% of beak shape variation. Similar beak shapes are associated with disparate dietary regimes, even when accounting for diet-feeding behavior relationships and phylogeny. Very few lineages optimize for stronger bite forces, with most birds exhibiting relatively fast, weak bites, even in large predatory taxa. The extreme morphological and behavioral flexibility of the beak in birds suggests that, far from being an exemplary feeding adaptation, avian beak diversification may have been largely contingent on trade-offs and constraints.}, } @article {pmid30536933, year = {2018}, author = {Brown, A and Akçay, E}, title = {Evolution of transmission mode in conditional mutualisms with spatial variation in symbiont quality.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13656}, pmid = {30536933}, issn = {1558-5646}, support = {Teaching Assistant Fellowship//University of Pennsylvania/ ; //Department of Defense/ ; Kek Futures Initiative//National Academy of Sciences/ ; }, abstract = {Many symbioses have costs and benefits to their hosts that vary with the environmental context, which itself may vary in space. The same symbiont may be a mutualist in one location and a parasite in another. Such spatially conditional mutualisms pose a dilemma for hosts, who might evolve (higher or lower) horizontal or vertical transmission to increase their chances of being infected only where the symbiont is beneficial. To determine how transmission in hosts might evolve, we modeled transmission evolution where the symbiont had a spatially conditional effect on either host lifespan or fecundity. We found that over ecological time, symbionts that affected lifespan but not fecundity led to high frequencies of infected hosts in areas where the symbiont was beneficial and low frequencies elsewhere. In response, hosts evolved increased horizontal transmission only when the symbiont affected lifespan. We also modeled transmission evolution in symbionts, which evolved high horizontal and vertical transmission, indicating a possible host-symbiont conflict over transmission mode. Our results suggest an eco-evolutionary feedback where the component of host fitness affected by a conditionally mutualistic symbiont in turn determines its distribution in the population, and, through this, the transmission mode that evolves.}, } @article {pmid30536929, year = {2018}, author = {Esquerré, D and Brennan, IG and Catullo, RA and Torres-Pérez, F and Keogh, JS}, title = {How mountains shape biodiversity: The role of the Andes in biogeography, diversification, and reproductive biology in South America's most species-rich lizard radiation (Squamata: Liolaemidae).}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13657}, pmid = {30536929}, issn = {1558-5646}, support = {//Becas Chile-CONICYT/ ; 1140929//FONDECYT/ ; }, abstract = {Testing hypotheses on drivers of clade evolution and trait diversification provides insight into many aspects of evolutionary biology. Often, studies investigate only intrinsic biological properties of organisms as the causes of diversity, however, extrinsic properties of a clade's environment, particularly geological history, may also offer compelling explanations. The Andes are a young mountain chain known to have shaped many aspects of climate and diversity of South America. The Liolaemidae are a radiation of South American reptiles with over 300 species found across most biomes and with similar numbers of egg-laying and live-bearing species. Using the most complete dated phylogeny of the family, we tested the role of Andean uplift in biogeography, diversification patterns, and parity mode of the Liolaemidae. We find that the Andes promoted lineage diversification and acted as a species pump into surrounding biomes. We also find strong support for the role of Andean uplift in boosting the species diversity of these lizards via allopatric fragmentation. Finally, we find repeated shifts in parity mode associated with changing thermal niches, with live-bearing favored in cold climates and egg-laying favored in warm climates. Importantly, we find evidence for possible reversals to oviparity, an evolutionary transition believed to be extremely rare.}, } @article {pmid30536693, year = {2018}, author = {Rajeev, L and Garber, ME and Zane, GM and Price, MN and Dubchak, I and Wall, JD and Novichkov, PS and Mukhopadhyay, A and Kazakov, AE}, title = {A new family of transcriptional regulators of tungstoenzymes and molybdate/tungstate transport.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14500}, pmid = {30536693}, issn = {1462-2920}, support = {//Office of Science/ ; //U.S. Department of Energy/ ; //Lawrence Berkeley National Laboratory/ ; }, abstract = {Bacterial genes for molybdenum-containing and tungsten-containing enzymes are often differentially regulated depending on the metal availability in the environment. Here, we describe a new family of transcription factors with an unusual DNA-binding domain related to excisionases of bacteriophages. These transcription factors are associated with genes for various molybdate and tungstate-specific transporting systems as well as molybdo/tungsto-enzymes in a wide range of bacterial genomes. We used a combination of computational and experimental techniques to study a member of the TF family, named TaoR (for tungsten-containing aldehyde oxidoreductase regulator). In Desulfovibrio vulgaris Hildenborough, a model bacterium for sulfate reduction studies, TaoR activates expression of aldehyde oxidoreductase aor and represses tungsten-specific ABC-type transporter tupABC genes under tungsten-replete conditions. TaoR binding sites at aor promoter were identified by electrophoretic mobility shift assay and DNase I footprinting. We also reconstructed TaoR regulons in 45 Deltaproteobacteria by comparative genomics approach and predicted target genes for TaoR family members in other Proteobacteria and Firmicutes.}, } @article {pmid30536518, year = {2018}, author = {Harris, KD and Kolodkin-Gal, I}, title = {Applying the handicap principle to biofilms: condition-dependent signalling in Bacillus subtilis microbial communities.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14497}, pmid = {30536518}, issn = {1462-2920}, support = {119/16ISF Icore 152-1//Israel Science Foundation/ ; }, abstract = {Bacteria in nature often reside in differentiated communities termed biofilms. These communities, which are composed of a number of functionally-distinct cell types, are an interesting example of division of labour in microbes, and as such have been used as a system to study the evolution of cooperation. The structured population of the biofilm also plays a critical role in the persistence of infections, and biofouling of medical and industrial devices. Biofilm formation involves several stages of differentiation, which are mediated by extracellular factors secreted by cells composing the biofilm. The developmental model of biofilm formation describes this process mechanistically: specific subpopulations of cells synthesize signals within the biofilm, and promote the differentiation of other subpopulations. The handicap principle suggests that signals function because they provide reliable information regarding the state of the signaller; here, we apply the handicap principle to signalling among cells composing Bacillus subtilis biofilms, emphasizing the perspective of secreted factors as sources of information rather than solely as mediators of development. Such information could facilitate competition among phenotypically-similar cells composing the biofilm, affecting local organizational patterns within defined subpopulations.}, } @article {pmid30535834, year = {2018}, author = {Zhang, X and Xu, M and Wu, J and Dong, W and Chen, D and Wang, L and Chi, Y}, title = {Draft Genome Sequence of Phoma arachidicola Wb2 Causing Peanut Web Blotch in China.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1612-z}, pmid = {30535834}, issn = {1432-0991}, support = {ZR2017PC015//Natural Science Foundation of Shandong Province/ ; ZR2018LC015//Natural Science Foundation of Shandong Province/ ; 17-3-3-70-nsh//Qingdao Foundation/ ; CXGC2018E21, 06210214442019, 2-18-43//Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Sciences/ ; SDAIT-04-07//Shandong Agriculture Research System/ ; 2017YFD0201608, 2016YFD0200504//National key scientific and technological project/ ; }, abstract = {Peanut web blotch, a peanut disease with both web and blotch symptom leaflets, is an emerging threat for peanut cultivation worldwide and one of the most important fungal diseases in China. However, the limited pieces of information in genomic resources and pathogenesis are the major constraints to integrated disease management. The genome contains a large number of pathogenicity-related genes, but the genomic information of the pathogen is still blank. Considering this fact, current study presented the draft genome sequence of a Phoma arachidicola isolate named Wb2. Strain Wb2 was isolated from peanut leaves with typical web blotch symptoms, and identified as Phoma arachidicola based on morphological characteristics and phylogenic analysis using ITS sequence. The draft genome of Wb2 is about 34.11 Mb and contains 37330 open reading frames (ORFs), with G + C content 49.23%. The strain Wb2 has an abundance of secreted oxidases, peroxidases, and carbohydrate-active enzymes for degrading cell wall polysaccharides and penetrating into the host tissue. The genome information of Wb2 will help to better understand the mechanisms of interaction between P. arachidicola and peanuts. Furthermore, the genome-based plant-pathogen interaction analysis will provide clues for disease control, which is essential to ensure peanut production and food security.}, } @article {pmid30535029, year = {2018}, author = {Liu, H and Maclean, CJ and Zhang, J}, title = {Evolution of the yeast recombination landscape.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy233}, pmid = {30535029}, issn = {1537-1719}, abstract = {Meiotic recombination comprises crossovers and non-crossovers. Recombination, crossover in particular, shuffles mutations and impacts both the level of genetic polymorphism and the speed of adaptation. In many species, the recombination rate varies across the genome with hot- and cold-spots. The hotspot paradox hypothesis asserts that recombination hotspots are evolutionarily unstable due to self-destruction. However, the genomic landscape of double-strand breaks (DSBs), which initiate recombination, is evolutionarily conserved among divergent yeast species, casting doubt on the hotspot paradox hypothesis. Nonetheless, because only a subset of DSBs are associated with crossovers, the evolutionary conservation of the crossover landscape could differ from that of DSBs. Here we investigate this possibility by generating a high-resolution recombination map of the budding yeast Saccharomyces paradoxus through whole-genome sequencing of fifty meiotic tetrads and by comparing this recombination map with that of S. cerevisiae. We observe a 40% lower recombination rate in S. paradoxus than in S. cerevisiae. Compared with the DSB landscape, the crossover landscape is even more conserved. Further analyses indicate that the elevated conservation of the crossover landscape is explained by a near-subtelomeric crossover preference in both yeasts, which we find to be attributable at least in part to crossover interference. We conclude that the yeast crossover landscape is highly conserved and that the evolutionary conservation of this landscape can differ from that of the DSB landscape.}, } @article {pmid30534351, year = {2018}, author = {Liang, J and Hoffrichter, A and Brachmann, A and Marín, M}, title = {Complete genome of Rhizobium leguminosarum Norway, an ineffective Lotus micro-symbiont.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {36}, pmid = {30534351}, issn = {1944-3277}, abstract = {Rhizobia bacteria engage in nitrogen-fixing root nodule symbiosis, a mutualistic interaction with legume plants in which a bidirectional nutrient exchange takes place. Occasionally, this interaction is suboptimal resulting in the formation of ineffective nodules in which little or no atmospheric nitrogen fixation occurs. Rhizobium leguminosarum Norway induces ineffective nodules in a wide range of Lotus hosts. To investigate the basis of this phenotype, we sequenced the complete genome of Rl Norway and compared it to the genome of the closely related strain R. leguminosarum bv. viciae 3841. The genome comprises 7,788,085 bp, distributed on a circular chromosome containing 63% of the genomic information and five large circular plasmids. The functionally classified bacterial gene set is distributed evenly among all replicons. All symbiotic genes (nod, fix, nif) are located on the pRLN3 plasmid. Whole genome comparisons revealed differences in the metabolic repertoire and in protein secretion systems, but not in classical symbiotic genes.}, } @article {pmid30532048, year = {2019}, author = {Prevéy, JS and Rixen, C and Rüger, N and Høye, TT and Bjorkman, AD and Myers-Smith, IH and Elmendorf, SC and Ashton, IW and Cannone, N and Chisholm, CL and Clark, K and Cooper, EJ and Elberling, B and Fosaa, AM and Henry, GHR and Hollister, RD and Jónsdóttir, IS and Klanderud, K and Kopp, CW and Lévesque, E and Mauritz, M and Molau, U and Natali, SM and Oberbauer, SF and Panchen, ZA and Post, E and Rumpf, SB and Schmidt, NM and Schuur, E and Semenchuk, PR and Smith, JG and Suding, KN and Totland, Ø and Troxler, T and Venn, S and Wahren, CH and Welker, JM and Wipf, S}, title = {Warming shortens flowering seasons of tundra plant communities.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {45-52}, doi = {10.1038/s41559-018-0745-6}, pmid = {30532048}, issn = {2397-334X}, abstract = {Advancing phenology is one of the most visible effects of climate change on plant communities, and has been especially pronounced in temperature-limited tundra ecosystems. However, phenological responses have been shown to differ greatly between species, with some species shifting phenology more than others. We analysed a database of 42,689 tundra plant phenological observations to show that warmer temperatures are leading to a contraction of community-level flowering seasons in tundra ecosystems due to a greater advancement in the flowering times of late-flowering species than early-flowering species. Shorter flowering seasons with a changing climate have the potential to alter trophic interactions in tundra ecosystems. Interestingly, these findings differ from those of warmer ecosystems, where early-flowering species have been found to be more sensitive to temperature change, suggesting that community-level phenological responses to warming can vary greatly between biomes.}, } @article {pmid30532047, year = {2019}, author = {Wu, N and Zhang, S and Li, X and Cao, Y and Liu, X and Wang, Q and Liu, Q and Liu, H and Hu, X and Zhou, XJ and James, AA and Zhang, Z and Huang, Y and Zhan, S}, title = {Fall webworm genomes yield insights into rapid adaptation of invasive species.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {105-115}, doi = {10.1038/s41559-018-0746-5}, pmid = {30532047}, issn = {2397-334X}, abstract = {Invasive species cause considerable ecological and economic damage. Despite decades of broad impacts of invasives on diversity and agriculture, the genetic adaptations and near-term evolution of invading populations are poorly understood. The fall webworm, Hyphantria cunea, a highly successful invasive species that originated in North America, spread throughout the Northern Hemisphere during the past 80 years. Here, we use whole-genome sequencing of invasive populations and transcriptome profiling to probe the underlying genetic bases for the rapid adaptation of this species to new environments and host plants. We find substantial reductions in genomic diversity consistent with founder effects. Genes and pathways associated with carbohydrate metabolism and gustatory receptors are substantially expanded in the webworm genome and show strong signatures of functional polymorphisms in the invasive population. We also find that silk-yielding-associated genes maintained a relatively low level of functional diversity, and identify candidate genes that may regulate the development of silk glands in fall webworms. These data suggest that the fall webworm's ability to colonize novel hosts, mediated by plasticity in their gustatory capabilities along with an increased ability to utilize novel nutrition sources and substrates, has facilitated the rapid and successful adaptation of the species throughout its range.}, } @article {pmid30532046, year = {2018}, author = {Halfwerk, W and Blaas, M and Kramer, L and Hijner, N and Trillo, PA and Bernal, XE and Page, RA and Goutte, S and Ryan, MJ and Ellers, J}, title = {Adaptive changes in sexual signalling in response to urbanization.}, journal = {Nature ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41559-018-0751-8}, pmid = {30532046}, issn = {2397-334X}, abstract = {Urbanization can cause species to adjust their sexual displays, because the effectiveness of mating signals is influenced by environmental conditions. Despite many examples that show that mating signals in urban conditions differ from those in rural conditions, we do not know whether these differences provide a combined reproductive and survival benefit to the urban phenotype. Here we show that male túngara frogs have increased the conspicuousness of their calls, which is under strong sexual and natural selection by signal receivers, as an adaptive response to city life. The urban phenotype consequently attracts more females than the forest phenotype, while avoiding the costs that are imposed by eavesdropping bats and midges, which we show are rare in urban areas. Finally, we show in a translocation experiment that urban frogs can reduce risk of predation and parasitism when moved to the forest, but that forest frogs do not increase their sexual attractiveness when moved to the city. Our findings thus reveal that urbanization can rapidly drive adaptive signal change via changes in both natural and sexual selection pressures.}, } @article {pmid30532043, year = {2019}, author = {Kolodny, O and Weinberg, M and Reshef, L and Harten, L and Hefetz, A and Gophna, U and Feldman, MW and Yovel, Y}, title = {Coordinated change at the colony level in fruit bat fur microbiomes through time.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {116-124}, doi = {10.1038/s41559-018-0731-z}, pmid = {30532043}, issn = {2397-334X}, abstract = {The host-associated microbiome affects individual health and behaviour, and may be influenced by local environmental conditions. However, little is known about microbiomes' temporal dynamics in free-living species compared with their dynamics in humans and model organisms, especially in body sites other than the gut. Here, we investigate longitudinal changes in the fur microbiome of captive and free-living Egyptian fruit bats. We find that, in contrast to patterns described in humans and other mammals, the prominent dynamics is of change over time at the level of the colony as a whole. On average, a pair of fur microbiome samples from different individuals in the same colony collected on the same date are more similar to one another than a pair of samples from the same individual collected at different time points. This pattern suggests that the whole colony may be the appropriate biological unit for understanding some of the roles of the host microbiome in social bats' ecology and evolution. This pattern of synchronized colony changes over time is also reflected in the profile of volatile compounds in the bats' fur, but differs from the more individualized pattern found in the bats' gut microbiome.}, } @article {pmid30532042, year = {2019}, author = {Rapacciuolo, G and Graham, CH and Marin, J and Behm, JE and Costa, GC and Hedges, SB and Helmus, MR and Radeloff, VC and Young, BE and Brooks, TM}, title = {Species diversity as a surrogate for conservation of phylogenetic and functional diversity in terrestrial vertebrates across the Americas.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {53-61}, doi = {10.1038/s41559-018-0744-7}, pmid = {30532042}, issn = {2397-334X}, abstract = {Preserving the evolutionary history and ecological functions that different species embody, in addition to species themselves, is a growing concern for conservation. Recent studies warn that conservation priority regions identified using species diversity differ from those based on phylogenetic or functional diversity. However, spatial mismatches in conservation priority regions need not indicate low surrogacy among these dimensions in conservation planning. Here, we use data for 10,213 terrestrial vertebrate species across the Americas to evaluate surrogacy; that is, the proportion of phylogenetic or functional diversity represented in conservation plans targeting species. We find that most conservation plans targeting species diversity also represent phylogenetic and functional diversity well, despite spatial mismatches in the priority regions identified by each plan. However, not all phylogenetic and functional diversity is represented within species-based plans, with the highest-surrogacy conservation strategy depending on the proportion of land area included in plans. Our results indicate that targeting species diversity could be sufficient to preserve much of the phylogenetic and functional dimensions of biodiversity in terrestrial vertebrates of the Americas. Incorporating phylogenetic and functional data in broad-scale conservation planning may not always be necessary, especially when the cost of doing so is high.}, } @article {pmid30532002, year = {2018}, author = {Collins, JL and Tadich, A and Wu, W and Gomes, LC and Rodrigues, JNB and Liu, C and Hellerstedt, J and Ryu, H and Tang, S and Mo, SK and Adam, S and Yang, SA and Fuhrer, MS and Edmonds, MT}, title = {Electric-field-tuned topological phase transition in ultrathin Na3Bi.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {390-394}, doi = {10.1038/s41586-018-0788-5}, pmid = {30532002}, issn = {1476-4687}, support = {DE-AC02-05CH11231//Department of Energy/International ; }, abstract = {The electric-field-induced quantum phase transition from topological to conventional insulator has been proposed as the basis of a topological field effect transistor1-4. In this scheme, 'on' is the ballistic flow of charge and spin along dissipationless edges of a two-dimensional quantum spin Hall insulator5-9, and 'off' is produced by applying an electric field that converts the exotic insulator to a conventional insulator with no conductive channels. Such a topological transistor is promising for low-energy logic circuits4, which would necessitate electric-field-switched materials with conventional and topological bandgaps much greater than the thermal energy at room temperature, substantially greater than proposed so far6-8. Topological Dirac semimetals are promising systems in which to look for topological field-effect switching, as they lie at the boundary between conventional and topological phases3,10-16. Here we use scanning tunnelling microscopy and spectroscopy and angle-resolved photoelectron spectroscopy to show that mono- and bilayer films of the topological Dirac semimetal3,17 Na3Bi are two-dimensional topological insulators with bulk bandgaps greater than 300 millielectronvolts owing to quantum confinement in the absence of electric field. On application of electric field by doping with potassium or by close approach of the scanning tunnelling microscope tip, the Stark effect completely closes the bandgap and re-opens it as a conventional gap of 90 millielectronvolts. The large bandgaps in both the conventional and quantum spin Hall phases, much greater than the thermal energy at room temperature (25 millielectronvolts), suggest that ultrathin Na3Bi is suitable for room-temperature topological transistor operation.}, } @article {pmid30532001, year = {2019}, author = {Huang, T and Lin, SH and Malewicz, NM and Zhang, Y and Zhang, Y and Goulding, M and LaMotte, RH and Ma, Q}, title = {Identifying the pathways required for coping behaviours associated with sustained pain.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {86-90}, doi = {10.1038/s41586-018-0793-8}, pmid = {30532001}, issn = {1476-4687}, support = {R01 DE018025/DE/NIDCR NIH HHS/United States ; R01 NS086372/NS/NINDS NIH HHS/United States ; 200183/Z/15/Z//Wellcome Trust/United Kingdom ; }, abstract = {Animals and humans display two types of response to noxious stimuli. The first includes reflexive defensive responses that prevent or limit injury; a well-known example of these responses is the quick withdrawal of one's hand upon touching a hot object. When the first-line response fails to prevent tissue damage (for example, a finger is burnt), the resulting pain invokes a second-line coping response-such as licking the injured area to soothe suffering. However, the underlying neural circuits that drive these two strings of behaviour remain poorly understood. Here we show in mice that spinal neurons marked by coexpression of TAC1Cre and LBX1Flpo drive coping responses associated with pain. Ablation of these spinal neurons led to the loss of both persistent licking and conditioned aversion evoked by stimuli (including skin pinching and burn injury) that-in humans-produce sustained pain, without affecting any of the reflexive defensive reactions that we tested. This selective indifference to sustained pain resembles the phenotype seen in humans with lesions of medial thalamic nuclei1-3. Consistently, spinal TAC1-lineage neurons are connected to medial thalamic nuclei by direct projections and via indirect routes through the superior lateral parabrachial nuclei. Furthermore, the anatomical and functional segregation observed at the spinal level also applies to primary sensory neurons. For example, in response to noxious mechanical stimuli, MRGPRD- and TRPV1-positive nociceptors are required to elicit reflexive and coping responses, respectively. Our study therefore reveals a fundamental subdivision within the cutaneous somatosensory system, and challenges the validity of using reflexive defensive responses to measure sustained pain.}, } @article {pmid30531980, year = {2018}, author = {Zhou, D and Zhao, Y and Kotecha, A and Fry, EE and Kelly, JT and Wang, X and Rao, Z and Rowlands, DJ and Ren, J and Stuart, DI}, title = {Unexpected mode of engagement between enterovirus 71 and its receptor SCARB2.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-018-0319-z}, pmid = {30531980}, issn = {2058-5276}, abstract = {Enterovirus 71 (EV71) is a common cause of hand, foot and mouth disease-a disease endemic especially in the Asia-Pacific region1. Scavenger receptor class B member 2 (SCARB2) is the major receptor of EV71, as well as several other enteroviruses responsible for hand, foot and mouth disease, and plays a key role in cell entry2. The isolated structures of EV71 and SCARB2 are known3-6, but how they interact to initiate infection is not. Here, we report the EV71-SCARB2 complex structure determined at 3.4 Å resolution using cryo-electron microscopy. This reveals that SCARB2 binds EV71 on the southern rim of the canyon, rather than across the canyon, as predicted3,7,8. Helices 152-163 (α5) and 183-193 (α7) of SCARB2 and the viral protein 1 (VP1) GH and VP2 EF loops of EV71 dominate the interaction, suggesting an allosteric mechanism by which receptor binding might facilitate the low-pH uncoating of the virus in the endosome/lysosome. Remarkably, many residues within the binding footprint are not conserved across SCARB2-dependent enteroviruses; however, a conserved proline and glycine seem to be key residues. Thus, although the virus maintains antigenic variability even within the receptor-binding footprint, the identification of binding 'hot spots' may facilitate the design of receptor mimic therapeutics less likely to quickly generate resistance.}, } @article {pmid30531979, year = {2019}, author = {Mathur, A and Feng, S and Hayward, JA and Ngo, C and Fox, D and Atmosukarto, II and Price, JD and Schauer, K and Märtlbauer, E and Robertson, AAB and Burgio, G and Fox, EM and Leppla, SH and Kaakoush, NO and Man, SM}, title = {A multicomponent toxin from Bacillus cereus incites inflammation and shapes host outcome via the NLRP3 inflammasome.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {362-374}, doi = {10.1038/s41564-018-0318-0}, pmid = {30531979}, issn = {2058-5276}, abstract = {Host recognition of microbial components is essential in mediating an effective immune response. Cytosolic bacteria must secure entry into the host cytoplasm to facilitate replication and, in doing so, liberate microbial ligands that activate cytosolic innate immune sensors and the inflammasome. Here, we identified a multicomponent enterotoxin, haemolysin BL (HBL), that engages activation of the inflammasome. This toxin is highly conserved among the human pathogen Bacillus cereus. The three subunits of HBL bind to the cell membrane in a linear order, forming a lytic pore and inducing activation of the NLRP3 inflammasome, secretion of interleukin-1β and interleukin-18, and pyroptosis. Mechanistically, the HBL-induced pore results in the efflux of potassium and triggers the activation of the NLRP3 inflammasome. Furthermore, HBL-producing B. cereus induces rapid inflammasome-mediated mortality. Pharmacological inhibition of the NLRP3 inflammasome using MCC950 prevents B. cereus-induced lethality. Overall, our results reveal that cytosolic sensing of a toxin is central to the innate immune recognition of infection. Therapeutic modulation of this pathway enhances host protection against deadly bacterial infections.}, } @article {pmid30531978, year = {2018}, author = {Park, SJ and Kim, YI and Park, A and Kwon, HI and Kim, EH and Si, YJ and Song, MS and Lee, CH and Jung, K and Shin, WJ and Zeng, J and Choi, Y and Jung, JU and Choi, YK}, title = {Ferret animal model of severe fever with thrombocytopenia syndrome phlebovirus for human lethal infection and pathogenesis.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-018-0317-1}, pmid = {30531978}, issn = {2058-5276}, abstract = {Severe fever with thrombocytopenia syndrome phlebovirus (SFTSV), listed in the most dangerous pathogens by the World Health Organization, has 12-30% fatality rates with a characteristic thrombocytopenia syndrome. With a majority of clinically diagnosed SFTSV patients older than ~50 years of age, age is a critical risk factor for SFTSV morbidity and mortality. Here, we report an age-dependent ferret model of SFTSV infection and pathogenesis that fully recapitulates the clinical manifestations of human infections. Whereas young adult ferrets (≤2 years of age) did not show any clinical symptoms and mortality, SFTSV-infected aged ferrets (≥4 years of age) demonstrated severe thrombocytopenia, reduced white blood cell counts and high fever with 93% mortality rate. Moreover, a significantly higher viral load was observed in aged ferrets. Transcriptome analysis of SFTSV-infected young ferrets revealed strong interferon-mediated anti-viral signalling, whereas inflammatory immune responses were markedly upregulated and persisted in aged ferrets. Thus, this immunocompetent age-dependent ferret model should be useful for anti-SFTSV therapy and vaccine development.}, } @article {pmid30531977, year = {2019}, author = {Kitzinger, K and Padilla, CC and Marchant, HK and Hach, PF and Herbold, CW and Kidane, AT and Könneke, M and Littmann, S and Mooshammer, M and Niggemann, J and Petrov, S and Richter, A and Stewart, FJ and Wagner, M and Kuypers, MMM and Bristow, LA}, title = {Cyanate and urea are substrates for nitrification by Thaumarchaeota in the marine environment.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {234-243}, doi = {10.1038/s41564-018-0316-2}, pmid = {30531977}, issn = {2058-5276}, abstract = {Ammonia-oxidizing archaea of the phylum Thaumarchaeota are among the most abundant marine microorganisms1. These organisms thrive in the oceans despite ammonium being present at low nanomolar concentrations2,3. Some Thaumarchaeota isolates have been shown to utilize urea and cyanate as energy and N sources through intracellular conversion to ammonium4-6. Yet, it is unclear whether patterns observed in culture extend to marine Thaumarchaeota, and whether Thaumarchaeota in the ocean directly utilize urea and cyanate or rely on co-occurring microorganisms to break these substrates down to ammonium. Urea utilization has been reported for marine ammonia-oxidizing communities7-10, but no evidence of cyanate utilization exists for marine ammonia oxidizers. Here, we demonstrate that in the Gulf of Mexico, Thaumarchaeota use urea and cyanate both directly and indirectly as energy and N sources. We observed substantial and linear rates of nitrite production from urea and cyanate additions, which often persisted even when ammonium was added to micromolar concentrations. Furthermore, single-cell analysis revealed that the Thaumarchaeota incorporated ammonium-, urea- and cyanate-derived N at significantly higher rates than most other microorganisms. Yet, no cyanases were detected in thaumarchaeal genomic data from the Gulf of Mexico. Therefore, we tested cyanate utilization in Nitrosopumilus maritimus, which also lacks a canonical cyanase, and showed that cyanate was oxidized to nitrite. Our findings demonstrate that marine Thaumarchaeota can use urea and cyanate as both an energy and N source. On the basis of these results, we hypothesize that urea and cyanate are substrates for ammonia-oxidizing Thaumarchaeota throughout the ocean.}, } @article {pmid30531976, year = {2019}, author = {Franzosa, EA and Sirota-Madi, A and Avila-Pacheco, J and Fornelos, N and Haiser, HJ and Reinker, S and Vatanen, T and Hall, AB and Mallick, H and McIver, LJ and Sauk, JS and Wilson, RG and Stevens, BW and Scott, JM and Pierce, K and Deik, AA and Bullock, K and Imhann, F and Porter, JA and Zhernakova, A and Fu, J and Weersma, RK and Wijmenga, C and Clish, CB and Vlamakis, H and Huttenhower, C and Xavier, RJ}, title = {Gut microbiome structure and metabolic activity in inflammatory bowel disease.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {293-305}, doi = {10.1038/s41564-018-0306-4}, pmid = {30531976}, issn = {2058-5276}, support = {R01 DK092405/DK/NIDDK NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; U01 DK097430/DK/NIDDK NIH HHS/United States ; U54 DK102557/DK/NIDDK NIH HHS/United States ; }, abstract = {The inflammatory bowel diseases (IBDs), which include Crohn's disease (CD) and ulcerative colitis (UC), are multifactorial chronic conditions of the gastrointestinal tract. While IBD has been associated with dramatic changes in the gut microbiota, changes in the gut metabolome-the molecular interface between host and microbiota-are less well understood. To address this gap, we performed untargeted metabolomic and shotgun metagenomic profiling of cross-sectional stool samples from discovery (n = 155) and validation (n = 65) cohorts of CD, UC and non-IBD control patients. Metabolomic and metagenomic profiles were broadly correlated with faecal calprotectin levels (a measure of gut inflammation). Across >8,000 measured metabolite features, we identified chemicals and chemical classes that were differentially abundant in IBD, including enrichments for sphingolipids and bile acids, and depletions for triacylglycerols and tetrapyrroles. While > 50% of differentially abundant metabolite features were uncharacterized, many could be assigned putative roles through metabolomic 'guilt by association' (covariation with known metabolites). Differentially abundant species and functions from the metagenomic profiles reflected adaptation to oxidative stress in the IBD gut, and were individually consistent with previous findings. Integrating these data, however, we identified 122 robust associations between differentially abundant species and well-characterized differentially abundant metabolites, indicating possible mechanistic relationships that are perturbed in IBD. Finally, we found that metabolome- and metagenome-based classifiers of IBD status were highly accurate and, like the vast majority of individual trends, generalized well to the independent validation cohort. Our findings thus provide an improved understanding of perturbations of the microbiome-metabolome interface in IBD, including identification of many potential diagnostic and therapeutic targets.}, } @article {pmid30531975, year = {2018}, author = {Strandwitz, P and Kim, KH and Terekhova, D and Liu, JK and Sharma, A and Levering, J and McDonald, D and Dietrich, D and Ramadhar, TR and Lekbua, A and Mroue, N and Liston, C and Stewart, EJ and Dubin, MJ and Zengler, K and Knight, R and Gilbert, JA and Clardy, J and Lewis, K}, title = {GABA-modulating bacteria of the human gut microbiota.}, journal = {Nature microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41564-018-0307-3}, pmid = {30531975}, issn = {2058-5276}, support = {R01 HG005824/HG/NHGRI NIH HHS/United States ; }, abstract = {The gut microbiota affects many important host functions, including the immune response and the nervous system1. However, while substantial progress has been made in growing diverse microorganisms of the microbiota2, 23-65% of species residing in the human gut remain uncultured3,4, which is an obstacle for understanding their biological roles. A likely reason for this unculturability is the absence in artificial media of key growth factors that are provided by neighbouring bacteria in situ5,6. In the present study, we used co-culture to isolate KLE1738, which required the presence of Bacteroides fragilis to grow. Bioassay-driven purification of B. fragilis supernatant led to the isolation of the growth factor, which, surprisingly, is the major inhibitory neurotransmitter GABA (γ-aminobutyric acid). GABA was the only tested nutrient that supported the growth of KLE1738, and a genome analysis supported a GABA-dependent metabolism mechanism. Using growth of KLE1738 as an indicator, we isolated a variety of GABA-producing bacteria, and found that Bacteroides ssp. produced large quantities of GABA. Genome-based metabolic modelling of the human gut microbiota revealed multiple genera with the predicted capability to produce or consume GABA. A transcriptome analysis of human stool samples from healthy individuals showed that GABA-producing pathways are actively expressed by Bacteroides, Parabacteroides and Escherichia species. By coupling 16S ribosmal RNA sequencing with functional magentic resonance imaging in patients with major depressive disorder, a disease associated with an altered GABA-mediated response, we found that the relative abundance levels of faecal Bacteroides are negatively correlated with brain signatures associated with depression.}, } @article {pmid30531948, year = {2018}, author = {Keller, NP}, title = {Fungal secondary metabolism: regulation, function and drug discovery.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0121-1}, pmid = {30531948}, issn = {1740-1534}, abstract = {One of the exciting movements in microbial sciences has been a refocusing and revitalization of efforts to mine the fungal secondary metabolome. The magnitude of biosynthetic gene clusters (BGCs) in a single filamentous fungal genome combined with the historic number of sequenced genomes suggests that the secondary metabolite wealth of filamentous fungi is largely untapped. Mining algorithms and scalable expression platforms have greatly expanded access to the chemical repertoire of fungal-derived secondary metabolites. In this Review, I discuss new insights into the transcriptional and epigenetic regulation of BGCs and the ecological roles of fungal secondary metabolites in warfare, defence and development. I also explore avenues for the identification of new fungal metabolites and the challenges in harvesting fungal-derived secondary metabolites.}, } @article {pmid30531947, year = {2018}, author = {Cui, J and Li, F and Shi, ZL}, title = {Origin and evolution of pathogenic coronaviruses.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0118-9}, pmid = {30531947}, issn = {1740-1534}, abstract = {Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) are two highly transmissible and pathogenic viruses that emerged in humans at the beginning of the 21st century. Both viruses likely originated in bats, and genetically diverse coronaviruses that are related to SARS-CoV and MERS-CoV were discovered in bats worldwide. In this Review, we summarize the current knowledge on the origin and evolution of these two pathogenic coronaviruses and discuss their receptor usage; we also highlight the diversity and potential of spillover of bat-borne coronaviruses, as evidenced by the recent spillover of swine acute diarrhoea syndrome coronavirus (SADS-CoV) to pigs.}, } @article {pmid30531886, year = {2018}, author = {}, title = {Maths shows how we lose interest.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {162}, doi = {10.1038/d41586-018-07719-w}, pmid = {30531886}, issn = {1476-4687}, } @article {pmid30531885, year = {2018}, author = {Tubiello, FN}, title = {COP24 and SDGs - use same statistics please.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {190}, doi = {10.1038/d41586-018-07721-2}, pmid = {30531885}, issn = {1476-4687}, } @article {pmid30531884, year = {2018}, author = {Nowogrodzki, A}, title = {The automatic-design tools that are changing synthetic biology.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {291-292}, doi = {10.1038/d41586-018-07662-w}, pmid = {30531884}, issn = {1476-4687}, } @article {pmid30531883, year = {2018}, author = {Kneebone, R and Schlegel, C and Spivey, A}, title = {Science in hand: how art and craft can boost reproducibility.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {188-189}, doi = {10.1038/d41586-018-07676-4}, pmid = {30531883}, issn = {1476-4687}, mesh = {Reproducibility of Results ; Research Design ; *Science ; }, } @article {pmid30531882, year = {2018}, author = {Barras, C}, title = {'Little Foot' hominin emerges from stone after millions of years.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {169-170}, doi = {10.1038/d41586-018-07651-z}, pmid = {30531882}, issn = {1476-4687}, } @article {pmid30531881, year = {2018}, author = {Maxmen, A}, title = {Ebola detectives race to identify hidden sources of infection as outbreak spreads.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {174-175}, doi = {10.1038/d41586-018-07618-0}, pmid = {30531881}, issn = {1476-4687}, } @article {pmid30531880, year = {2018}, author = {Reardon, S}, title = {Machine learning helps to hunt down the cause of a paralysing illness.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {170-171}, doi = {10.1038/d41586-018-07631-3}, pmid = {30531880}, issn = {1476-4687}, } @article {pmid30531879, year = {2018}, author = {Ledford, H}, title = {Cancer researchers seek to harness mysterious DNA 'super-enhancers'.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {173-174}, doi = {10.1038/d41586-018-07602-8}, pmid = {30531879}, issn = {1476-4687}, } @article {pmid30531878, year = {2018}, author = {Clokie, MRJ}, title = {Bacterial defence molecules target viral DNA.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {199-200}, doi = {10.1038/d41586-018-07576-7}, pmid = {30531878}, issn = {1476-4687}, } @article {pmid30531877, year = {2018}, author = {Fozouni, P and Ott, M}, title = {How cells hush a viral invader.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {193-194}, doi = {10.1038/d41586-018-07493-9}, pmid = {30531877}, issn = {1476-4687}, mesh = {*DNA ; Diagnostic Tests, Routine ; *Retroviridae ; }, } @article {pmid30531876, year = {2018}, author = {Spurgin, LG and Chapman, T}, title = {Darwin's finches choose parent lookalikes as mates.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {196-197}, doi = {10.1038/d41586-018-07494-8}, pmid = {30531876}, issn = {1476-4687}, mesh = {Animals ; Finches ; *Reproduction ; *Sexual Behavior ; }, } @article {pmid30531872, year = {2019}, author = {Fanucchi, S and Fok, ET and Dalla, E and Shibayama, Y and Börner, K and Chang, EY and Stoychev, S and Imakaev, M and Grimm, D and Wang, KC and Li, G and Sung, WK and Mhlanga, MM}, title = {Immune genes are primed for robust transcription by proximal long noncoding RNAs located in nuclear compartments.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {138-150}, doi = {10.1038/s41588-018-0298-2}, pmid = {30531872}, issn = {1546-1718}, abstract = {Accumulation of trimethylation of histone H3 at lysine 4 (H3K4me3) on immune-related gene promoters underlies robust transcription during trained immunity. However, the molecular basis for this remains unknown. Here we show three-dimensional chromatin topology enables immune genes to engage in chromosomal contacts with a subset of long noncoding RNAs (lncRNAs) we have defined as immune gene-priming lncRNAs (IPLs). We show that the prototypical IPL, UMLILO, acts in cis to direct the WD repeat-containing protein 5 (WDR5)-mixed lineage leukemia protein 1 (MLL1) complex across the chemokine promoters, facilitating their H3K4me3 epigenetic priming. This mechanism is shared amongst several trained immune genes. Training mediated by β-glucan epigenetically reprograms immune genes by upregulating IPLs in manner dependent on nuclear factor of activated T cells. The murine chemokine topologically associating domain lacks an IPL, and the Cxcl genes are not trained. Strikingly, the insertion of UMLILO into the chemokine topologically associating domain in mouse macrophages resulted in training of Cxcl genes. This provides strong evidence that lncRNA-mediated regulation is central to the establishment of trained immunity.}, } @article {pmid30531871, year = {2019}, author = {Nayar, U and Cohen, O and Kapstad, C and Cuoco, MS and Waks, AG and Wander, SA and Painter, C and Freeman, S and Persky, NS and Marini, L and Helvie, K and Oliver, N and Rozenblatt-Rosen, O and Ma, CX and Regev, A and Winer, EP and Lin, NU and Wagle, N}, title = {Acquired HER2 mutations in ER+ metastatic breast cancer confer resistance to estrogen receptor-directed therapies.}, journal = {Nature genetics}, volume = {51}, number = {2}, pages = {207-216}, doi = {10.1038/s41588-018-0287-5}, pmid = {30531871}, issn = {1546-1718}, abstract = {Seventy percent of breast cancers express the estrogen receptor (ER), and agents that target the ER are the mainstay of treatment. However, virtually all people with ER+ breast cancer develop resistance to ER-directed agents in the metastatic setting. Beyond mutations in the ER itself, which occur in 25-30% of people treated with aromatase inhibitors1-4, knowledge about clinical resistance mechanisms remains incomplete. We identified activating HER2 mutations in metastatic biopsies from eight patients with ER+ metastatic breast cancer who had developed resistance to aromatase inhibitors, tamoxifen or fulvestrant. Examination of treatment-naive primary tumors in five patients showed no evidence of pre-existing mutations in four of five patients, suggesting that these mutations were acquired under the selective pressure of ER-directed therapy. The HER2 mutations and ER mutations were mutually exclusive, suggesting a distinct mechanism of acquired resistance to ER-directed therapies. In vitro analysis confirmed that the HER2 mutations conferred estrogen independence as well as-in contrast to ER mutations-resistance to tamoxifen, fulvestrant and the CDK4 and CDK6 inhibitor palbociclib. Resistance was overcome by combining ER-directed therapy with the irreversible HER2 kinase inhibitor neratinib.}, } @article {pmid30531870, year = {2019}, author = {Havrilla, JM and Pedersen, BS and Layer, RM and Quinlan, AR}, title = {A map of constrained coding regions in the human genome.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {88-95}, doi = {10.1038/s41588-018-0294-6}, pmid = {30531870}, issn = {1546-1718}, abstract = {Deep catalogs of genetic variation from thousands of humans enable the detection of intraspecies constraint by identifying coding regions with a scarcity of variation. While existing techniques summarize constraint for entire genes, single gene-wide metrics conceal regional constraint variability within each gene. Therefore, we have created a detailed map of constrained coding regions (CCRs) by leveraging variation observed among 123,136 humans from the Genome Aggregation Database. The most constrained CCRs are enriched for pathogenic variants in ClinVar and mutations underlying developmental disorders. CCRs highlight protein domain families under high constraint and suggest unannotated or incomplete protein domains. The highest-percentile CCRs complement existing variant prioritization methods when evaluating de novo mutations in studies of autosomal dominant disease. Finally, we identify highly constrained CCRs within genes lacking known disease associations. This observation suggests that CCRs may identify regions under strong purifying selection that, when mutated, cause severe developmental phenotypes or embryonic lethality.}, } @article {pmid30530702, year = {2018}, author = {Purdy, MD and Shi, D and Chrustowicz, J and Hattne, J and Gonen, T and Yeager, M}, title = {MicroED structures of HIV-1 Gag CTD-SP1 reveal binding interactions with the maturation inhibitor bevirimat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13258-13263}, doi = {10.1073/pnas.1806806115}, pmid = {30530702}, issn = {1091-6490}, support = {P41 GM103311/GM/NIGMS NIH HHS/United States ; R01 GM066087/GM/NIGMS NIH HHS/United States ; P50 GM082545/GM/NIGMS NIH HHS/United States ; R01 GM128507/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {HIV-1 protease (PR) cleavage of the Gag polyprotein triggers the assembly of mature, infectious particles. Final cleavage of Gag occurs at the junction helix between the capsid protein CA and the SP1 spacer peptide. Here we used MicroED to delineate the binding interactions of the maturation inhibitor bevirimat (BVM) using very thin frozen-hydrated, 3D microcrystals of a CTD-SP1 Gag construct with and without bound BVM. The 2.9-Å MicroED structure revealed that a single BVM molecule stabilizes the six-helix bundle via both electrostatic interactions with the dimethylsuccinyl moiety and hydrophobic interactions with the pentacyclic triterpenoid ring. These results provide insight into the mechanism of action of BVM and related maturation inhibitors that will inform further drug discovery efforts. This study also demonstrates the capabilities of MicroED for structure-based drug design.}, } @article {pmid30530701, year = {2018}, author = {Liu, Y and Sheng, J and van Vliet, ALW and Buda, G and van Kuppeveld, FJM and Rossmann, MG}, title = {Molecular basis for the acid-initiated uncoating of human enterovirus D68.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12209-E12217}, doi = {10.1073/pnas.1803347115}, pmid = {30530701}, issn = {1091-6490}, abstract = {Enterovirus D68 (EV-D68) belongs to a group of enteroviruses that contain a single positive-sense RNA genome surrounded by an icosahedral capsid. Like common cold viruses, EV-D68 mainly causes respiratory infections and is acid-labile. The molecular mechanism by which the acid-sensitive EV-D68 virions uncoat and deliver their genome into a host cell is unknown. Using cryoelectron microscopy (cryo-EM), we have determined the structures of the full native virion and an uncoating intermediate [the A (altered) particle] of EV-D68 at 2.2- and 2.7-Å resolution, respectively. These structures showed that acid treatment of EV-D68 leads to particle expansion, externalization of the viral protein VP1 N termini from the capsid interior, and formation of pores around the icosahedral twofold axes through which the viral RNA can exit. Moreover, because of the low stability of EV-D68, cryo-EM analyses of a mixed population of particles at neutral pH and following acid treatment demonstrated the involvement of multiple structural intermediates during virus uncoating. Among these, a previously undescribed state, the expanded 1 ("E1") particle, shows a majority of internal regions (e.g., the VP1 N termini) to be ordered as in the full native virion. Thus, the E1 particle acts as an intermediate in the transition from full native virions to A particles. Together, the present work delineates the pathway of EV-D68 uncoating and provides the molecular basis for the acid lability of EV-D68 and of the related common cold viruses.}, } @article {pmid30530700, year = {2018}, author = {Negre, CFA and Morzan, UN and Hendrickson, HP and Pal, R and Lisi, GP and Loria, JP and Rivalta, I and Ho, J and Batista, VS}, title = {Eigenvector centrality for characterization of protein allosteric pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12201-E12208}, doi = {10.1073/pnas.1810452115}, pmid = {30530700}, issn = {1091-6490}, abstract = {Determining the principal energy-transfer pathways responsible for allosteric communication in biomolecules remains challenging, partially due to the intrinsic complexity of the systems and the lack of effective characterization methods. In this work, we introduce the eigenvector centrality metric based on mutual information to elucidate allosteric mechanisms that regulate enzymatic activity. Moreover, we propose a strategy to characterize the range of correlations that underlie the allosteric processes. We use the V-type allosteric enzyme imidazole glycerol phosphate synthase (IGPS) to test the proposed methodology. The eigenvector centrality method identifies key amino acid residues of IGPS with high susceptibility to effector binding. The findings are validated by solution NMR measurements yielding important biological insights, including direct experimental evidence for interdomain motion, the central role played by helix h[Formula: see text], and the short-range nature of correlations responsible for the allosteric mechanism. Beyond insights on IGPS allosteric pathways and the nature of residues that could be targeted by therapeutic drugs or site-directed mutagenesis, the reported findings demonstrate the eigenvector centrality analysis as a general cost-effective methodology to gain fundamental understanding of allosteric mechanisms at the molecular level.}, } @article {pmid30530699, year = {2018}, author = {Hogle, SL and Dupont, CL and Hopkinson, BM and King, AL and Buck, KN and Roe, KL and Stuart, RK and Allen, AE and Mann, EL and Johnson, ZI and Barbeau, KA}, title = {Pervasive iron limitation at subsurface chlorophyll maxima of the California Current.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13300-13305}, doi = {10.1073/pnas.1813192115}, pmid = {30530699}, issn = {1091-6490}, abstract = {Subsurface chlorophyll maximum layers (SCMLs) are nearly ubiquitous in stratified water columns and exist at horizontal scales ranging from the submesoscale to the extent of oligotrophic gyres. These layers of heightened chlorophyll and/or phytoplankton concentrations are generally thought to be a consequence of a balance between light energy from above and a limiting nutrient flux from below, typically nitrate (NO3). Here we present multiple lines of evidence demonstrating that iron (Fe) limits or with light colimits phytoplankton communities in SCMLs along a primary productivity gradient from coastal to oligotrophic offshore waters in the southern California Current ecosystem. SCML phytoplankton responded markedly to added Fe or Fe/light in experimental incubations and transcripts of diatom and picoeukaryote Fe stress genes were strikingly abundant in SCML metatranscriptomes. Using a biogeochemical proxy with data from a 40-y time series, we find that diatoms growing in California Current SCMLs are persistently Fe deficient during the spring and summer growing season. We also find that the spatial extent of Fe deficiency within California Current SCMLs has significantly increased over the last 25 y in line with a regional climate index. Finally, we show that diatom Fe deficiency may be common in the subsurface of major upwelling zones worldwide. Our results have important implications for our understanding of the biogeochemical consequences of marine SCML formation and maintenance.}, } @article {pmid30530698, year = {2018}, author = {Qu, M and Duffy, T and Hirota, T and Kay, SA}, title = {Nuclear receptor HNF4A transrepresses CLOCK:BMAL1 and modulates tissue-specific circadian networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12305-E12312}, doi = {10.1073/pnas.1816411115}, pmid = {30530698}, issn = {1091-6490}, abstract = {Either expression level or transcriptional activity of various nuclear receptors (NRs) have been demonstrated to be under circadian control. With a few exceptions, little is known about the roles of NRs as direct regulators of the circadian circuitry. Here we show that the nuclear receptor HNF4A strongly transrepresses the transcriptional activity of the CLOCK:BMAL1 heterodimer. We define a central role for HNF4A in maintaining cell-autonomous circadian oscillations in a tissue-specific manner in liver and colon cells. Not only transcript level but also genome-wide chromosome binding of HNF4A is rhythmically regulated in the mouse liver. ChIP-seq analyses revealed cooccupancy of HNF4A and CLOCK:BMAL1 at a wide array of metabolic genes involved in lipid, glucose, and amino acid homeostasis. Taken together, we establish that HNF4A defines a feedback loop in tissue-specific mammalian oscillators and demonstrate its recruitment in the circadian regulation of metabolic pathways.}, } @article {pmid30530697, year = {2018}, author = {Surnar, B and Basu, U and Banik, B and Ahmad, A and Marples, B and Kolishetti, N and Dhar, S}, title = {Nanotechnology-mediated crossing of two impermeable membranes to modulate the stars of the neurovascular unit for neuroprotection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12333-E12342}, doi = {10.1073/pnas.1816429115}, pmid = {30530697}, issn = {1091-6490}, abstract = {The success of nanoparticle-mediated delivery of antioxidant and antiinflammatory-based neuroprotectants to the brain to improve neuronal functions in neurodegenerative diseases has demonstrated lesser impact instead of achieving its full potential. We hypothesized that these failures were due to a combination of parameters, such as: (i) unavailability of a delivery vehicle, which can reproducibly and efficiently transport through the brain capillary endothelium; (ii) inefficient uptake of therapeutic nanoparticles in the neuronal cell population; and (iii) limited ability of a single nanoparticle to cross the two most-impermeable biological barriers, the blood-brain barrier and mitochondrial double membrane, so that a nanoparticle can travel through the brain endothelial barrier to the mitochondria of target cells where oxidative damage is localized. Herein, we demonstrate optimization of a biodegradable nanoparticle for efficient brain accumulation and protection of astrocytes from oxidative damage and mitochondrial dysfunctions to enhance the neuroprotection ability of astrocytes toward neurons using neurodegeneration characteristics in SOD1G93A rats. This biodegradable nanomedicine platform with the ability to accumulate in the brain has the potential to bring beneficial effects in neurodegenerative diseases by modulating the stars, astrocytes in the brain, to enhance their neuroprotective actions.}, } @article {pmid30530696, year = {2018}, author = {Heo, L and Feig, M}, title = {Experimental accuracy in protein structure refinement via molecular dynamics simulations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13276-13281}, doi = {10.1073/pnas.1811364115}, pmid = {30530696}, issn = {1091-6490}, support = {R01 GM084953/GM/NIGMS NIH HHS/United States ; R35 GM126948/GM/NIGMS NIH HHS/United States ; }, abstract = {Refinement is the last step in protein structure prediction pipelines to convert approximate homology models to experimental accuracy. Protocols based on molecular dynamics (MD) simulations have shown promise, but current methods are limited to moderate levels of consistent refinement. To explore the energy landscape between homology models and native structures and analyze the challenges of MD-based refinement, eight test cases were studied via extensive simulations followed by Markov state modeling. In all cases, native states were found very close to the experimental structures and at the lowest free energies, but refinement was hindered by a rough energy landscape. Transitions from the homology model to the native states require the crossing of significant kinetic barriers on at least microsecond time scales. A significant energetic driving force toward the native state was lacking until its immediate vicinity, and there was significant sampling of off-pathway states competing for productive refinement. The role of recent force field improvements is discussed and transition paths are analyzed in detail to inform which key transitions have to be overcome to achieve successful refinement.}, } @article {pmid30530695, year = {2018}, author = {Tarduno, JA}, title = {Subterranean clues to the future of our planetary magnetic shield.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13154-13156}, doi = {10.1073/pnas.1819025116}, pmid = {30530695}, issn = {1091-6490}, } @article {pmid30530694, year = {2018}, author = {Lin, YC and Wang, Y and Hsu, R and Giri, S and Wopat, S and Arif, MK and Chakraborty, A and Prasanth, KV and Prasanth, SG}, title = {PCNA-mediated stabilization of E3 ligase RFWD3 at the replication fork is essential for DNA replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13282-13287}, doi = {10.1073/pnas.1814521115}, pmid = {30530694}, issn = {1091-6490}, abstract = {RING finger and WD repeat domain-containing protein 3 (RFWD3) is an E3 ligase known to facilitate homologous recombination by removing replication protein A (RPA) and RAD51 from DNA damage sites. Further, RPA-mediated recruitment of RFWD3 to stalled replication forks is essential for interstrand cross-link repair. Here, we report that in unperturbed human cells, RFWD3 localizes at replication forks and associates with proliferating cell nuclear antigen (PCNA) via its PCNA-interacting protein (PIP) motif. PCNA association is critical for the stability of RFWD3 and for DNA replication. Cells lacking RFWD3 show slower fork progression, a prolonged S phase, and an increase in the loading of several replication-fork components on the chromatin. These findings all point to increased frequency of stalled forks in the absence of RFWD3. The S-phase defect is rescued by WT RFWD3, but not by the PIP mutant, suggesting that the interaction of RFWD3 with PCNA is critical for DNA replication. Finally, we observe reduced ubiquitination of RPA in cells lacking RFWD3. We conclude that the stabilization of RFWD3 by PCNA at the replication fork enables the polyubiquitination of RPA and its subsequent degradation for proper DNA replication.}, } @article {pmid30530693, year = {2018}, author = {Keller, S and Korkmaz, G and Robbins, C and Shipp, S}, title = {Opportunities to observe and measure intangible inputs to innovation: Definitions, operationalization, and examples.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12638-12645}, doi = {10.1073/pnas.1800467115}, pmid = {30530693}, issn = {1091-6490}, abstract = {Measuring the value of intangibles is not easy, because they are critical but usually invisible components of the innovation process. Today, access to nonsurvey data sources, such as administrative data and repositories captured on web pages, opens opportunities to create intangibles based on new sources of information and capture intangible innovations in new ways. Intangibles include ownership of innovative property and human resources that make a company unique but are currently unmeasured. For example, intangibles represent the value of a company's databases and software, the tacit knowledge of their workers, and the investments in research and development (R&D) and design. Through two case studies, the challenges and processes to both create and measure intangibles are presented using a data science framework that outlines processes to discover, acquire, profile, clean, link, explore the fitness-for-use, and statistically analyze the data. The first case study shows that creating organizational innovation is possible by linking administrative data across business processes in a Fortune 500 company. The motivation for this research is to develop company processes capable of synchronizing their supply chain end to end while capturing dynamics that can alter the inventory, profits, and service balance. The second example shows the feasibility of measurement of innovation related to the characteristics of open source software through data scraped from software repositories that provide this information. The ultimate goal is to develop accurate and repeatable measures to estimate the value of nonbusiness sector open source software to the economy. This early work shows the feasibility of these approaches.}, } @article {pmid30530692, year = {2018}, author = {Klein, N and O'Brien, E}, title = {People use less information than they think to make up their minds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13222-13227}, doi = {10.1073/pnas.1805327115}, pmid = {30530692}, issn = {1091-6490}, abstract = {A world where information is abundant promises unprecedented opportunities for information exchange. Seven studies suggest these opportunities work better in theory than in practice: People fail to anticipate how quickly minds change, believing that they and others will evaluate more evidence before making up their minds than they and others actually do. From evaluating peers, marriage prospects, and political candidates to evaluating novel foods, goods, and services, people consume far less information than expected before deeming things good or bad. Accordingly, people acquire and share too much information in impression-formation contexts: People overvalue long-term trials, overpay for decision aids, and overwork to impress others, neglecting the speed at which conclusions will form. In today's information age, people may intuitively believe that exchanging ever-more information will foster better-informed opinions and perspectives-but much of this information may be lost on minds long made up.}, } @article {pmid30530691, year = {2018}, author = {Milojević, S and Radicchi, F and Walsh, JP}, title = {Changing demographics of scientific careers: The rise of the temporary workforce.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12616-12623}, doi = {10.1073/pnas.1800478115}, pmid = {30530691}, issn = {1091-6490}, abstract = {Contemporary science has been characterized by an exponential growth in publications and a rise of team science. At the same time, there has been an increase in the number of awarded PhD degrees, which has not been accompanied by a similar expansion in the number of academic positions. In such a competitive environment, an important measure of academic success is the ability to maintain a long active career in science. In this paper, we study workforce trends in three scientific disciplines over half a century. We find dramatic shortening of careers of scientists across all three disciplines. The time over which half of the cohort has left the field has shortened from 35 y in the 1960s to only 5 y in the 2010s. In addition, we find a rapid rise (from 25 to 60% since the 1960s) of a group of scientists who spend their entire career only as supporting authors without having led a publication. Altogether, the fraction of entering researchers who achieve full careers has diminished, while the class of temporary scientists has escalated. We provide an interpretation of our empirical results in terms of a survival model from which we infer potential factors of success in scientific career survivability. Cohort attrition can be successfully modeled by a relatively simple hazard probability function. Although we find statistically significant trends between survivability and an author's early productivity, neither productivity nor the citation impact of early work or the level of initial collaboration can serve as a reliable predictor of ultimate survivability.}, } @article {pmid30530690, year = {2018}, author = {Wang, H and Liu, X and Chen, S and Ye, K}, title = {Spatiotemporal activation of the C/EBPβ/δ-secretase axis regulates the pathogenesis of Alzheimer's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12427-E12434}, doi = {10.1073/pnas.1815915115}, pmid = {30530690}, issn = {1091-6490}, abstract = {Alzheimer's disease (AD) neuropathological hallmarks include senile plaques with aggregated amyloid beta as a major component, neurofibrillary tangles (NFT) containing truncated and hyperphosphorylated Tau, extensive neuronal loss, and chronic neuroinflammation. However, the key molecular mechanism that dominates the pathogenesis of AD remains elusive for AD. Here we show that the C/EBPβ/δ-secretase axis is activated in an age-dependent manner in different brain regions of the 3×Tg AD mouse model, elevating δ-secretase-truncated APP and Tau proteolytic truncates and promoting senile plaques and NFT formation in the brain, associated with gradual neuronal loss and chronic neuroinflammation. Depletion of inflammatory cytokine-regulated transcription factor C/EBPβ from 3×Tg mice represses APP, Tau, and δ-secretase expression, which subsequently inhibits APP and Tau cleavage, leading to mitigation of AD pathologies. Knockout of δ-secretase from 3×Tg mice strongly blunts AD pathogenesis. Consequently, inactivation of the C/EBPβ/δ-secretase axis ameliorates cognitive dysfunctions in 3×Tg mice by blocking APP and Tau expression and their pathological fragmentation. Thus, our findings support the notion that C/EBPβ/δ-secretase axis plays a crucial role in AD pathogenesis.}, } @article {pmid30530689, year = {2018}, author = {Hof, C and Voskamp, A and Biber, MF and Böhning-Gaese, K and Engelhardt, EK and Niamir, A and Willis, SG and Hickler, T}, title = {Bioenergy cropland expansion may offset positive effects of climate change mitigation for global vertebrate diversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13294-13299}, doi = {10.1073/pnas.1807745115}, pmid = {30530689}, issn = {1091-6490}, abstract = {Climate and land-use change interactively affect biodiversity. Large-scale expansions of bioenergy have been suggested as an important component for climate change mitigation. Here we use harmonized climate and land-use projections to investigate their potential combined impacts on global vertebrate diversity under a low- and a high-level emission scenario. We combine climate-based species distribution models for the world's amphibians, birds, and mammals with land-use change simulations and identify areas threatened by both climate and land-use change in the future. The combined projected effects of climate and land-use change on vertebrate diversity are similar under the two scenarios, with land-use change effects being stronger under the low- and climate change effects under the high-emission scenario. Under the low-emission scenario, increases in bioenergy cropland may cause severe impacts in biodiversity that are not compensated by lower climate change impacts. Under this low-emission scenario, larger proportions of species distributions and a higher number of small-range species may become impacted by the combination of land-use and climate change than under the high-emission scenario, largely a result of bioenergy cropland expansion. Our findings highlight the need to carefully consider both climate and land-use change when projecting biodiversity impacts. We show that biodiversity is likely to suffer severely if bioenergy cropland expansion remains a major component of climate change mitigation strategies. Our study calls for an immediate and significant reduction in energy consumption for the benefit of both biodiversity and to achieve the goals of the Paris Agreement.}, } @article {pmid30530688, year = {2019}, author = {Cerioli, A and Barabesi, L and Cerasa, A and Menegatti, M and Perrotta, D}, title = {Newcomb-Benford law and the detection of frauds in international trade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {106-115}, doi = {10.1073/pnas.1806617115}, pmid = {30530688}, issn = {1091-6490}, abstract = {The contrast of fraud in international trade is a crucial task of modern economic regulations. We develop statistical tools for the detection of frauds in customs declarations that rely on the Newcomb-Benford law for significant digits. Our first contribution is to show the features, in the context of a European Union market, of the traders for which the law should hold in the absence of fraudulent data manipulation. Our results shed light on a relevant and debated question, since no general known theory can exactly predict validity of the law for genuine empirical data. We also provide approximations to the distribution of test statistics when the Newcomb-Benford law does not hold. These approximations open the door to the development of modified goodness-of-fit procedures with wide applicability and good inferential properties.}, } @article {pmid30530687, year = {2018}, author = {Oh, YM and Mahar, M and Ewan, EE and Leahy, KM and Zhao, G and Cavalli, V}, title = {Epigenetic regulator UHRF1 inactivates REST and growth suppressor gene expression via DNA methylation to promote axon regeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12417-E12426}, doi = {10.1073/pnas.1812518115}, pmid = {30530687}, issn = {1091-6490}, abstract = {Injured peripheral sensory neurons switch to a regenerative state after axon injury, which requires transcriptional and epigenetic changes. However, the roles and mechanisms of gene inactivation after injury are poorly understood. Here, we show that DNA methylation, which generally leads to gene silencing, is required for robust axon regeneration after peripheral nerve lesion. Ubiquitin-like containing PHD ring finger 1 (UHRF1), a critical epigenetic regulator involved in DNA methylation, increases upon axon injury and is required for robust axon regeneration. The increased level of UHRF1 results from a decrease in miR-9. The level of another target of miR-9, the transcriptional regulator RE1 silencing transcription factor (REST), transiently increases after injury and is required for axon regeneration. Mechanistically, UHRF1 interacts with DNA methyltransferases (DNMTs) and H3K9me3 at the promoter region to repress the expression of the tumor suppressor gene phosphatase and tensin homolog (PTEN) and REST. Our study reveals an epigenetic mechanism that silences tumor suppressor genes and restricts REST expression in time after injury to promote axon regeneration.}, } @article {pmid30530686, year = {2018}, author = {Ron-Harel, N and Notarangelo, G and Ghergurovich, JM and Paulo, JA and Sage, PT and Santos, D and Satterstrom, FK and Gygi, SP and Rabinowitz, JD and Sharpe, AH and Haigis, MC}, title = {Defective respiration and one-carbon metabolism contribute to impaired naïve T cell activation in aged mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13347-13352}, doi = {10.1073/pnas.1804149115}, pmid = {30530686}, issn = {1091-6490}, support = {R01 GM067945/GM/NIGMS NIH HHS/United States ; }, abstract = {T cell-mediated immune responses are compromised in aged individuals, leading to increased morbidity and reduced response to vaccination. While cellular metabolism tightly regulates T cell activation and function, metabolic reprogramming in aged T cells has not been thoroughly studied. Here, we report a systematic analysis of metabolism during young versus aged naïve T cell activation. We observed a decrease in the number and activation of naïve T cells isolated from aged mice. While young T cells demonstrated robust mitochondrial biogenesis and respiration upon activation, aged T cells generated smaller mitochondria with lower respiratory capacity. Using quantitative proteomics, we defined the aged T cell proteome and discovered a specific deficit in the induction of enzymes of one-carbon metabolism. The activation of aged naïve T cells was enhanced by addition of products of one-carbon metabolism (formate and glycine). These studies define mechanisms of skewed metabolic remodeling in aged T cells and provide evidence that modulation of metabolism has the potential to promote immune function in aged individuals.}, } @article {pmid30530685, year = {2018}, author = {Burke, KD and Williams, JW and Chandler, MA and Haywood, AM and Lunt, DJ and Otto-Bliesner, BL}, title = {Pliocene and Eocene provide best analogs for near-future climates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13288-13293}, doi = {10.1073/pnas.1809600115}, pmid = {30530685}, issn = {1091-6490}, abstract = {As the world warms due to rising greenhouse gas concentrations, the Earth system moves toward climate states without societal precedent, challenging adaptation. Past Earth system states offer possible model systems for the warming world of the coming decades. These include the climate states of the Early Eocene (ca. 50 Ma), the Mid-Pliocene (3.3-3.0 Ma), the Last Interglacial (129-116 ka), the Mid-Holocene (6 ka), preindustrial (ca. 1850 CE), and the 20th century. Here, we quantitatively assess the similarity of future projected climate states to these six geohistorical benchmarks using simulations from the Hadley Centre Coupled Model Version 3 (HadCM3), the Goddard Institute for Space Studies Model E2-R (GISS), and the Community Climate System Model, Versions 3 and 4 (CCSM) Earth system models. Under the Representative Concentration Pathway 8.5 (RCP8.5) emission scenario, by 2030 CE, future climates most closely resemble Mid-Pliocene climates, and by 2150 CE, they most closely resemble Eocene climates. Under RCP4.5, climate stabilizes at Pliocene-like conditions by 2040 CE. Pliocene-like and Eocene-like climates emerge first in continental interiors and then expand outward. Geologically novel climates are uncommon in RCP4.5 (<1%) but reach 8.7% of the globe under RCP8.5, characterized by high temperatures and precipitation. Hence, RCP4.5 is roughly equivalent to stabilizing at Pliocene-like climates, while unmitigated emission trajectories, such as RCP8.5, are similar to reversing millions of years of long-term cooling on the scale of a few human generations. Both the emergence of geologically novel climates and the rapid reversion to Eocene-like climates may be outside the range of evolutionary adaptive capacity.}, } @article {pmid30530684, year = {2018}, author = {Martinez, W}, title = {How science and technology developments impact employment and education.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12624-12629}, doi = {10.1073/pnas.1803216115}, pmid = {30530684}, issn = {1091-6490}, abstract = {A better understanding of how developments in science and technology influence the creation of new occupations and subsequent changes in educational programs can help decision makers at all levels of our society. As a result of research and development efforts, innovations are achieved, resulting in the creation of new occupations and the demand for employees with expertise in these new areas. To fulfill the demand, universities and colleges often revise their programs to address these needs. Several data sources are described in this paper that might help us to explore the relationship between advancements in industry, emerging occupations, and educational changes over time.}, } @article {pmid30530683, year = {2018}, author = {Börner, K and Rouse, WB and Trunfio, P and Stanley, HE}, title = {Forecasting innovations in science, technology, and education.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12573-12581}, doi = {10.1073/pnas.1818750115}, pmid = {30530683}, issn = {1091-6490}, } @article {pmid30530682, year = {2018}, author = {Madhavan, G and Phelps, CE and Rouse, WB and Rappuoli, R}, title = {Vision for a systems architecture to integrate and transform population health.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12595-12602}, doi = {10.1073/pnas.1809919115}, pmid = {30530682}, issn = {1091-6490}, abstract = {Entities involved in population health often share a common mission while acting independently of one another and perhaps redundantly. Population health is in everybody's interest, but nobody is really in charge of promoting it. Across governments, corporations, and frontline operations, lack of coordination, lack of resources, and lack of reliable, current information have often impeded the development of situation-awareness models and thus a broad operational integration for population health. These deficiencies may also affect the technical, organizational, policy, and legal arrangements for information sharing, a desired practice of high potential value in population health. In this article, we articulate a vision for a next-generation modeling effort to create a systems architecture for broadly integrating and visualizing strategies for advancing population health. This multipurpose systems architecture would enable different views, alerts, and scenarios to better prepare for and respond to potential degradations in population health. We draw inspiration from systems engineering and visualization tools currently in other uses, including monitoring the state of the economy (market performance), security (classified intelligence), energy (power generation), transportation (global air traffic control), environment (weather monitoring), jobs (labor market dynamics), manufacturing and supply chain (tracking of components, parts, subassemblies, and products), and democratic processes (election analytics). We envision the basic ingredients for a population health systems architecture and its visualization dashboards to eventually support proactive planning and joint action among constituents. We intend our ambitious vision to encourage the work needed for progress that the population deserves.}, } @article {pmid30530681, year = {2018}, author = {Shneiderman, B}, title = {Twin-Win Model: A human-centered approach to research success.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12590-12594}, doi = {10.1073/pnas.1802918115}, pmid = {30530681}, issn = {1091-6490}, abstract = {A 70-year-old simmering debate has erupted into vigorous battles over the most effective ways to conduct research. Well-established beliefs are being forcefully challenged by advocates of new research models. While there can be no final resolution to this battle, this paper offers the Twin-Win Model to guide teams of researchers, academic leaders, business managers, and government funding policymakers. The Twin-Win Model favors a problem-oriented approach to research, which encourages formation of teams to pursue the dual goals of breakthrough theories in published papers and validated solutions that are ready for widespread dissemination. The raised expectations of simultaneously pursuing foundational discoveries and powerful innovations are a step beyond traditional approaches that advocate basic research first. Evidence from citation analysis and researcher interviews suggests that simultaneous pursuit of both goals raises the chance of twin-win success.}, } @article {pmid30530680, year = {2018}, author = {Lüdecke, T and Kullmer, O and Wacker, U and Sandrock, O and Fiebig, J and Schrenk, F and Mulch, A}, title = {Dietary versatility of Early Pleistocene hominins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13330-13335}, doi = {10.1073/pnas.1809439115}, pmid = {30530680}, issn = {1091-6490}, abstract = {New geochemical data from the Malawi Rift (Chiwondo Beds, Karonga Basin) fill a major spatial gap in our knowledge of hominin adaptations on a continental scale. Oxygen (δ18O), carbon (δ13C), and clumped (Δ47) isotope data on paleosols, hominins, and selected fauna elucidate an unexpected diversity in the Pleistocene hominin diet in the various habitats of the East African Rift System (EARS). Food sources of early Homo and Paranthropus thriving in relatively cool and wet wooded savanna ecosystems along the western shore of paleolake Malawi contained a large fraction of C3 plant material. Complementary water consumption reconstructions suggest that ca. 2.4 Ma, early Homo (Homo rudolfensis) and Paranthropus (Paranthropus boisei) remained rather stationary near freshwater sources along the lake margins. Time-equivalent Paranthropus aethiopicus from the Eastern Rift further north in the EARS consumed a higher fraction of C4 resources, an adaptation that grew more pronounced with increasing openness of the savanna setting after 2 Ma, while Homo maintained a high versatility. However, southern African Paranthropus robustus had, similar to the Malawi Rift individuals, C3-dominated feeding strategies throughout the Early Pleistocene. Collectively, the stable isotope and faunal data presented here document that early Homo and Paranthropus were dietary opportunists and able to cope with a wide range of paleohabitats, which clearly demonstrates their high behavioral flexibility in the African Early Pleistocene.}, } @article {pmid30530679, year = {2018}, author = {Zhang, Y and Hu, X and Islam, S and She, M and Peng, Y and Yu, Z and Wylie, S and Juhasz, A and Dowla, M and Yang, R and Zhang, J and Wang, X and Dell, B and Chen, X and Nevo, E and Sun, D and Ma, W}, title = {New insights into the evolution of wheat avenin-like proteins in wild emmer wheat (Triticum dicoccoides).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13312-13317}, doi = {10.1073/pnas.1812855115}, pmid = {30530679}, issn = {1091-6490}, abstract = {Fifteen full-length wheat grain avenin-like protein coding genes (TaALP) were identified on chromosome arms 7AS, 4AL, and 7DS of bread wheat with each containing five genes. Besides the a- and b-type ALPs, a c type was identified in the current paper. Both a and b types have two subunits, named x and y types. The five genes on each of the three chromosome arms consisted of two x-type genes, two y-type genes, and one c-type gene. The a-type genes were typically of 520 bp in length, whereas the b types were of 850 bp in length, and the c type was of 470 bp in length. The ALP gene transcript levels were significantly up-regulated in Blumeria graminis f. sp. tritici (Bgt)-infected wheat grain caryopsis at early grain filling. Wild emmer wheat [(WEW), Triticum dicoccoides] populations were focused on in our paper to identify allelic variations of ALP genes and to study the influence of natural selection on certain alleles. Consequently, 25 alleles were identified for TdALP-bx-7AS, 13 alleles were identified for TdALP-ax-7AS, 7 alleles were identified for TdALP-ay-7AS, and 4 alleles were identified for TdALP-ax-4AL Correlation studies on TdALP gene diversity and ecological stresses suggested that environmental factors contribute to the ALP polymorphism formation in WEW. Many allelic variants of ALPs in the endosperm of WEW are not present in bread wheat and therefore could be utilized in breeding bread wheat varieties for better quality and elite plant defense characteristics.}, } @article {pmid30530678, year = {2018}, author = {Fu, X and Sokolova, V and Webb, KJ and Old, W and Park, S}, title = {Ubiquitin-dependent switch during assembly of the proteasomal ATPases mediated by Not4 ubiquitin ligase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13246-13251}, doi = {10.1073/pnas.1805353115}, pmid = {30530678}, issn = {1091-6490}, abstract = {In the proteasome holoenzyme, the hexameric ATPases (Rpt1-Rpt6) enable degradation of ubiquitinated proteins by unfolding and translocating them into the proteolytic core particle. During early-stage proteasome assembly, individual Rpt proteins assemble into the hexameric "Rpt ring" through binding to their cognate chaperones: Nas2, Hsm3, Nas6, and Rpn14. Here, we show that Rpt ring assembly employs a specific ubiquitination-mediated control. An E3 ligase, Not4, selectively ubiquitinates Rpt5 during Rpt ring assembly. To access Rpt5, Not4 competes with Nas2 until the penultimate step and then with Hsm3 at the final step of Rpt ring completion. Using the known Rpt-chaperone cocrystal structures, we show that Not4-mediated ubiquitination sites in Rpt5 are obstructed by Nas2 and Hsm3. Thus, Not4 can distinguish a Rpt ring that matures without these chaperones, based on its accessibility to Rpt5. Rpt5 ubiquitination does not destabilize the ring but hinders incorporation of incoming subunits-Rpn1 ubiquitin receptor and Ubp6 deubiquitinase-thereby blocking progression of proteasome assembly and ubiquitin regeneration from proteasome substrates. Our findings reveal an assembly checkpoint where Not4 monitors chaperone actions during hexameric ATPase ring assembly, thereby ensuring the accuracy of proteasome holoenzyme maturation.}, } @article {pmid30530677, year = {2018}, author = {Olmos, LE and Çolak, S and Shafiei, S and Saberi, M and González, MC}, title = {Macroscopic dynamics and the collapse of urban traffic.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12654-12661}, doi = {10.1073/pnas.1800474115}, pmid = {30530677}, issn = {1091-6490}, abstract = {Stories of mega-jams that last tens of hours or even days appear not only in fiction but also in reality. In this context, it is important to characterize the collapse of the network, defined as the transition from a characteristic travel time to orders of magnitude longer for the same distance traveled. In this multicity study, we unravel this complex phenomenon under various conditions of demand and translate it to the travel time of the individual drivers. First, we start with the current conditions, showing that there is a characteristic time τ that takes a representative group of commuters to arrive at their destinations once their maximum density has been reached. While this time differs from city to city, it can be explained by Γ, defined as the ratio of the vehicle miles traveled to the total vehicle distance the road network can support per hour. Modifying Γ can improve τ and directly inform planning and infrastructure interventions. In this study we focus on measuring the vulnerability of the system by increasing the volume of cars in the network, keeping the road capacity and the empirical spatial dynamics from origins to destinations unchanged. We identify three states of urban traffic, separated by two distinctive transitions. The first one describes the appearance of the first bottlenecks and the second one the collapse of the system. This collapse is marked by a given number of commuters in each city and it is formally characterized by a nonequilibrium phase transition.}, } @article {pmid30530676, year = {2018}, author = {Sekara, V and Deville, P and Ahnert, SE and Barabási, AL and Sinatra, R and Lehmann, S}, title = {The chaperone effect in scientific publishing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12603-12607}, doi = {10.1073/pnas.1800471115}, pmid = {30530676}, issn = {1091-6490}, abstract = {Experience plays a critical role in crafting high-impact scientific work. This is particularly evident in top multidisciplinary journals, where a scientist is unlikely to appear as senior author if he or she has not previously published within the same journal. Here, we develop a quantitative understanding of author order by quantifying this "chaperone effect," capturing how scientists transition into senior status within a particular publication venue. We illustrate that the chaperone effect has a different magnitude for journals in different branches of science, being more pronounced in medical and biological sciences and weaker in natural sciences. Finally, we show that in the case of high-impact venues, the chaperone effect has significant implications, specifically resulting in a higher average impact relative to papers authored by new principal investigators (PIs). Our findings shed light on the role played by experience in publishing within specific scientific journals, on the paths toward acquiring the necessary experience and expertise, and on the skills required to publish in prestigious venues.}, } @article {pmid30530675, year = {2018}, author = {Trindade, RIF and Jaqueto, P and Terra-Nova, F and Brandt, D and Hartmann, GA and Feinberg, JM and Strauss, BE and Novello, VF and Cruz, FW and Karmann, I and Cheng, H and Edwards, RL}, title = {Speleothem record of geomagnetic South Atlantic Anomaly recurrence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13198-13203}, doi = {10.1073/pnas.1809197115}, pmid = {30530675}, issn = {1091-6490}, abstract = {The diminishing strength of the Earth's magnetic dipole over recent millennia is accompanied by the increasing prominence of the geomagnetic South Atlantic Anomaly (SAA), which spreads over the South Atlantic Ocean and South America. The longevity of this feature at millennial timescales is elusive because of the scarcity of continuous geomagnetic data for the region. Here, we report a unique geomagnetic record for the last ∼1500 y that combines the data of two well-dated stalagmites from Pau d'Alho cave, located close to the present-day minimum of the anomaly in central South America. Magnetic directions and relative paleointensity data for both stalagmites are generally consistent and agree with historical data from the last 500 y. Before 1500 CE, the data adhere to the geomagnetic model ARCH3K.1, which is derived solely from archeomagnetic data. Our observations indicate rapid directional variations (>0.1°/y) from approximately 860 to 960 CE and approximately 1450 to 1750 CE. A similar pattern of rapid directional variation observed from South Africa precedes the South American record by 224 ± 50 y. These results confirm that fast geomagnetic field variations linked to the SAA are a recurrent feature in the region. We develop synthetic models of reversed magnetic flux patches at the core-mantle boundary and calculate their expression at the Earth's surface. The models that qualitatively resemble the observational data involve westward (and southward) migration of midlatitude patches, combined with their expansion and intensification.}, } @article {pmid30530674, year = {2018}, author = {Hua, LL and Mikawa, T}, title = {Mitotic antipairing of homologous and sex chromosomes via spatial restriction of two haploid sets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12235-E12244}, doi = {10.1073/pnas.1809583115}, pmid = {30530674}, issn = {1091-6490}, abstract = {Pairing homologous chromosomes is required for recombination. However, in nonmeiotic stages it can lead to detrimental consequences, such as allelic misregulation and genome instability, and is rare in human somatic cells. How mitotic recombination is prevented-and how genetic stability is maintained across daughter cells-is a fundamental, unanswered question. Here, we report that both human and mouse cells impede homologous chromosome pairing by keeping two haploid chromosome sets apart throughout mitosis. Four-dimensional analysis of chromosomes during cell division revealed that a haploid chromosome set resides on either side of a meridional plane, crossing two centrosomes. Simultaneous tracking of chromosome oscillation and the spindle axis, using fluorescent CENP-A and centrin1, respectively, demonstrates collective genome behavior/segregation of two haploid sets throughout mitosis. Using 3D chromosome imaging of a translocation mouse with a supernumerary chromosome, we found that this maternally derived chromosome is positioned by parental origin. These data, taken together, support the identity of haploid sets by parental origin. This haploid set-based antipairing motif is shared by multiple cell types, doubles in tetraploid cells, and is lost in a carcinoma cell line. The data support a mechanism of nuclear polarity that sequesters two haploid sets along a subcellular axis. This topological segregation of haploid sets revisits an old model/paradigm and provides implications for maintaining mitotic fidelity.}, } @article {pmid30530673, year = {2018}, author = {Luganini, A and Di Nardo, G and Munaron, L and Gilardi, G and Fiorio Pla, A and Gribaudo, G}, title = {Human cytomegalovirus US21 protein is a viroporin that modulates calcium homeostasis and protects cells against apoptosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12370-E12377}, doi = {10.1073/pnas.1813183115}, pmid = {30530673}, issn = {1091-6490}, abstract = {The human cytomegalovirus (HCMV) US12 gene family comprises a set of 10 contiguous genes (US12 to US21) with emerging roles in the regulation of virus cell tropism, virion composition, and immunoevasion. Of all of the US12 gene products, pUS21 shows the highest level of identity with two cellular transmembrane BAX inhibitor motif-containing (TMBIM) proteins: Bax inhibitor-1 and Golgi anti-apoptotic protein, both of which are involved in the regulation of cellular Ca2+ homeostasis and adaptive cell responses to stress conditions. Here, we report the US21 protein to be a viral-encoded ion channel that regulates intracellular Ca2+ homeostasis and protects cells against apoptosis. Indeed, we show pUS21 to be a 7TMD protein expressed with late kinetics that accumulates in ER-derived vesicles. Deletion or inactivation of the US21 gene resulted in reduced HCMV growth, even in fibroblasts, due to reduced gene expression. Ratiometric fluorescence imaging assays revealed that expression of pUS21 reduces the Ca2+ content of intracellular ER stores. An increase in cell resistance to intrinsic apoptosis was then observed as an important cytobiological consequence of the pUS21-mediated alteration of intracellular Ca2+ homeostasis. Moreover, a single point mutation in the putative pore of pUS21 impaired the reduction of ER Ca2+ concentration and attenuated the antiapoptotic activity of pUS21wt, supporting a functional link with its ability to manipulate Ca2+ homeostasis. Together, these results suggest pUS21 of HCMV constitutes a TMBIM-derived viroporin that may contribute to HCMV's overall strategy to counteract apoptosis in infected cells.}, } @article {pmid30530672, year = {2018}, author = {Lee, JH and Phelan, P and Shin, M and Oh, BC and Han, X and Im, SS and Osborne, TF}, title = {SREBP-1a-stimulated lipid synthesis is required for macrophage phagocytosis downstream of TLR4-directed mTORC1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12228-E12234}, doi = {10.1073/pnas.1813458115}, pmid = {30530672}, issn = {1091-6490}, abstract = {There is a growing appreciation for a fundamental connection between lipid metabolism and the immune response. Macrophage phagocytosis is a signature innate immune response to pathogen exposure, and cytoplasmic membrane expansion is required to engulf the phagocytic target. The sterol regulatory element binding proteins (SREBPs) are key transcriptional regulatory proteins that sense the intracellular lipid environment and modulate expression of key genes of fatty acid and cholesterol metabolism to maintain lipid homeostasis. In this study, we show that TLR4-dependent stimulation of macrophage phagocytosis requires mTORC1-directed SREBP-1a-dependent lipid synthesis. We also show that the phagocytic defect in macrophages from SREBP-1a-deficient mice results from decreased interaction between membrane lipid rafts and the actin cytoskeleton, presumably due to reduced accumulation of newly synthesized fatty acyl chains within major membrane phospholipids. We show that mTORC1-deficient macrophages also have a phagocytic block downstream from TLR4 signaling, and, interestingly, the reduced level of phagocytosis in both SREBP-1a- and mTORC1-deficient macrophages can be restored by ectopic SREBP-1a expression. Taken together, these observations indicate SREBP-1a is a major downstream effector of TLR4-mTORC1 directed interactions between membrane lipid rafts and the actin cytoskeleton that are required for pathogen-stimulated phagocytosis in macrophages.}, } @article {pmid30530671, year = {2018}, author = {}, title = {Correction to Supporting Information for Fan et al., External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12121}, doi = {10.1073/pnas.1819671116}, pmid = {30530671}, issn = {1091-6490}, } @article {pmid30530670, year = {2018}, author = {Jara-Figueroa, C and Jun, B and Glaeser, EL and Hidalgo, CA}, title = {The role of industry-specific, occupation-specific, and location-specific knowledge in the growth and survival of new firms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12646-12653}, doi = {10.1073/pnas.1800475115}, pmid = {30530670}, issn = {1091-6490}, abstract = {How do regions acquire the knowledge they need to diversify their economic activities? How does the migration of workers among firms and industries contribute to the diffusion of that knowledge? Here we measure the industry-, occupation-, and location-specific knowledge carried by workers from one establishment to the next, using a dataset summarizing the individual work history for an entire country. We study pioneer firms-firms operating in an industry that was not present in a region-because the success of pioneers is the basic unit of regional economic diversification. We find that the growth and survival of pioneers increase significantly when their first hires are workers with experience in a related industry and with work experience in the same location, but not with past experience in a related occupation. We compare these results with new firms that are not pioneers and find that industry-specific knowledge is significantly more important for pioneer than for nonpioneer firms. To address endogeneity we use Bartik instruments, which leverage national fluctuations in the demand for an activity as shocks for local labor supply. The instrumental variable estimates support the finding that industry-specific knowledge is a predictor of the survival and growth of pioneer firms. These findings expand our understanding of the micromechanisms underlying regional economic diversification.}, } @article {pmid30530669, year = {2018}, author = {Vera-Chang, MN and St-Jacques, AD and Gagné, R and Martyniuk, CJ and Yauk, CL and Moon, TW and Trudeau, VL}, title = {Transgenerational hypocortisolism and behavioral disruption are induced by the antidepressant fluoxetine in male zebrafish Danio rerio.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12435-E12442}, doi = {10.1073/pnas.1811695115}, pmid = {30530669}, issn = {1091-6490}, abstract = {The global prevalence of depression is high during childbearing. Due to the associated risks to the mother and baby, the selective serotonin reuptake inhibitor fluoxetine (FLX) is often the first line of treatment. Given that FLX readily crosses the placenta, a fetus may be susceptible to the disruptive effects of FLX during this highly plastic stage of development. Here, we demonstrate that a 6-day FLX exposure to a fetus-relevant concentration at a critical developmental stage suppresses cortisol levels in the adult zebrafish (F0). This effect persists for three consecutive generations in the unexposed descendants (F1 to F3) without diminution and is more pronounced in males. We also show that the in vivo cortisol response of the interrenal (fish "adrenal") to an i.p. injection of adrenocorticotropic hormone was also reduced in the males from the F0 and F3 FLX lineages. Transcriptomic profiling of the whole kidney containing the interrenal cells revealed that early FLX exposure significantly modified numerous pathways closely associated with cortisol synthesis in the male adults from the F0 and F3 generations. We also show that the low cortisol levels are linked to significantly reduced exploratory behaviors in adult males from the F0 to F2 FLX lineages. This may be a cause for concern given the high prescription rates of FLX to pregnant women and the potential long-term negative impacts on humans exposed to these therapeutic drugs.}, } @article {pmid30530668, year = {2018}, author = {Rouse, WB and Lombardi, JV and Craig, DD}, title = {Modeling research universities: Predicting probable futures of public vs. private and large vs. small research universities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12582-12589}, doi = {10.1073/pnas.1807174115}, pmid = {30530668}, issn = {1091-6490}, abstract = {The future of the American academic research enterprise is considered. Data are presented that characterize the resources available for the 160 best-resourced research universities, a small subset of the 2,285 4-year, nonprofit, higher education institutions. A computational model of research universities was extended and used to simulate three strategic scenarios: status quo, steady decline in foreign graduate student enrollments, and downward tuition pressures from high-quality, online professional master's programs. Four specific universities are modeled: large public and private, and small public and private. The former are at the top of the 160 in terms of resources, while the latter are at the bottom of the 160. The model's projections suggest how universities might address these competitive forces. In some situations, it would be in the economic interests of these universities to restrict research activities to avoid the inherent subsidies these activities require. The computational projections portend the need for fundamental change of approaches to business for universities without large institutional resources.}, } @article {pmid30530667, year = {2018}, author = {Börner, K and Scrivner, O and Gallant, M and Ma, S and Liu, X and Chewning, K and Wu, L and Evans, JA}, title = {Skill discrepancies between research, education, and jobs reveal the critical need to supply soft skills for the data economy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12630-12637}, doi = {10.1073/pnas.1804247115}, pmid = {30530667}, issn = {1091-6490}, support = {P01 AG039347/AG/NIA NIH HHS/United States ; }, abstract = {Rapid research progress in science and technology (S&T) and continuously shifting workforce needs exert pressure on each other and on the educational and training systems that link them. Higher education institutions aim to equip new generations of students with skills and expertise relevant to workforce participation for decades to come, but their offerings sometimes misalign with commercial needs and new techniques forged at the frontiers of research. Here, we analyze and visualize the dynamic skill (mis-)alignment between academic push, industry pull, and educational offerings, paying special attention to the rapidly emerging areas of data science and data engineering (DS/DE). The visualizations and computational models presented here can help key decision makers understand the evolving structure of skills so that they can craft educational programs that serve workforce needs. Our study uses millions of publications, course syllabi, and job advertisements published between 2010 and 2016. We show how courses mediate between research and jobs. We also discover responsiveness in the academic, educational, and industrial system in how skill demands from industry are as likely to drive skill attention in research as the converse. Finally, we reveal the increasing importance of uniquely human skills, such as communication, negotiation, and persuasion. These skills are currently underexamined in research and undersupplied through education for the labor market. In an increasingly data-driven economy, the demand for "soft" social skills, like teamwork and communication, increase with greater demand for "hard" technical skills and tools.}, } @article {pmid30530666, year = {2018}, author = {Ma, Y and Uzzi, B}, title = {Scientific prize network predicts who pushes the boundaries of science.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12608-12615}, doi = {10.1073/pnas.1800485115}, pmid = {30530666}, issn = {1091-6490}, support = {R01 GM112938/GM/NIGMS NIH HHS/United States ; }, abstract = {Scientific prizes confer credibility to persons, ideas, and disciplines, provide financial incentives, and promote community-building celebrations. We examine the growth dynamics and interlocking relationships found in the worldwide scientific prize network. We focus on understanding how the knowledge linkages among prizes and scientists' propensities for prizewinning relate to knowledge pathways between disciplines and stratification within disciplines. Our data cover more than 3,000 different scientific prizes in diverse disciplines and the career histories of 10,455 prizewinners worldwide for over 100 years. We find several key links between prizes and scientific advances. First, despite an explosive proliferation of prizes over time and across the globe, prizes are more concentrated within a relatively small group of scientific elites, and ties among elites are highly clustered, suggesting that a relatively constrained number of ideas and scholars push the boundaries of science. For example, 64.1% of prizewinners have won two prizes and 13.7% have won five or more prizes. Second, certain prizes strongly interlock disciplines and subdisciplines, creating key pathways by which knowledge spreads and is recognized across science. Third, genealogical and coauthorship networks predict who wins multiple prizes, which helps to explain the interconnectedness among celebrated scientists and their pathbreaking ideas.}, } @article {pmid30530665, year = {2018}, author = {Lin, M and Siford, RL and Martin, AR and Nakagome, S and Möller, M and Hoal, EG and Bustamante, CD and Gignoux, CR and Henn, BM}, title = {Rapid evolution of a skin-lightening allele in southern African KhoeSan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13324-13329}, doi = {10.1073/pnas.1801948115}, pmid = {30530665}, issn = {1091-6490}, abstract = {Skin pigmentation is under strong directional selection in northern European and Asian populations. The indigenous KhoeSan populations of far southern Africa have lighter skin than other sub-Saharan African populations, potentially reflecting local adaptation to a region of Africa with reduced UV radiation. Here, we demonstrate that a canonical Eurasian skin pigmentation gene, SLC24A5, was introduced to southern Africa via recent migration and experienced strong adaptive evolution in the KhoeSan. To reconstruct the evolution of skin pigmentation, we collected phenotypes from over 400 ≠Khomani San and Nama individuals and high-throughput sequenced candidate pigmentation genes. The derived causal allele in SLC24A5, p.Ala111Thr, significantly lightens basal skin pigmentation in the KhoeSan and explains 8 to 15% of phenotypic variance in these populations. The frequency of this allele (33 to 53%) is far greater than expected from colonial period European gene flow; however, the most common derived haplotype is identical among European, eastern African, and KhoeSan individuals. Using four-population demographic simulations with selection, we show that the allele was introduced into the KhoeSan only 2,000 y ago via a back-to-Africa migration and then experienced a selective sweep (s = 0.04 to 0.05 in ≠Khomani and Nama). The SLC24A5 locus is both a rare example of intense, ongoing adaptation in very recent human history, as well as an adaptive gene flow at a pigmentation locus in humans.}, } @article {pmid30530664, year = {2018}, author = {Copur, Ö and Gorchakov, A and Finkl, K and Kuroda, MI and Müller, J}, title = {Sex-specific phenotypes of histone H4 point mutants establish dosage compensation as the critical function of H4K16 acetylation in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13336-13341}, doi = {10.1073/pnas.1817274115}, pmid = {30530664}, issn = {1091-6490}, abstract = {Acetylation of histone H4 at lysine 16 (H4K16) modulates nucleosome-nucleosome interactions and directly affects nucleosome binding by certain proteins. In Drosophila, H4K16 acetylation by the dosage compensation complex subunit Mof is linked to increased transcription of genes on the single X chromosome in males. Here, we analyzed Drosophila containing different H4K16 mutations or lacking Mof protein. An H4K16A mutation causes embryonic lethality in both sexes, whereas an H4K16R mutation permits females to develop into adults but causes lethality in males. The acetyl-mimic mutation H4K16Q permits both females and males to develop into adults. Complementary analyses reveal that males lacking maternally deposited and zygotically expressed Mof protein arrest development during gastrulation, whereas females of the same genotype develop into adults. Together, this demonstrates the causative role of H4K16 acetylation by Mof for dosage compensation in Drosophila and uncovers a previously unrecognized requirement for this process already during the onset of zygotic gene transcription.}, } @article {pmid30530663, year = {2018}, author = {Juan-Colás, J and Hitchcock, IS and Coles, M and Johnson, S and Krauss, TF}, title = {Quantifying single-cell secretion in real time using resonant hyperspectral imaging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13204-13209}, doi = {10.1073/pnas.1814977115}, pmid = {30530663}, issn = {1091-6490}, support = {MC_PC_15073//Medical Research Council/International ; }, abstract = {Cell communication is primarily regulated by secreted proteins, whose inhomogeneous secretion often indicates physiological disorder. Parallel monitoring of innate protein-secretion kinetics from individual cells is thus crucial to unravel systemic malfunctions. Here, we report a label-free, high-throughput method for parallel, in vitro, and real-time analysis of specific single-cell signaling using hyperspectral photonic crystal resonant technology. Heterogeneity in physiological thrombopoietin expression from individual HepG2 liver cells in response to platelet desialylation was quantified demonstrating how mapping real-time protein secretion can provide a simple, yet powerful approach for studying complex physiological systems regulating protein production at single-cell resolution.}, } @article {pmid30530662, year = {2018}, author = {Schmickl, T and Karsai, I}, title = {Integral feedback control is at the core of task allocation and resilience of insect societies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13180-13185}, doi = {10.1073/pnas.1807684115}, pmid = {30530662}, issn = {1091-6490}, abstract = {Homeostatic self-regulation is a fundamental aspect of open dissipative systems. Integral feedback has been found to be important for homeostatic control on both the cellular and molecular levels of biological organization and in engineered systems. Analyzing the task allocation mechanisms of three insect societies, we identified a model of integral control residing at colony level. We characterized a general functional core mechanism, called the "common stomach," where a crucial shared substance for colony function self-regulates its own quantity via reallocating the colony's workforce, which collects and uses this substance. The central component in a redundant feedback network is the saturation level of this substance in the colony. An interaction network of positive and negative feedback loops ensures the homeostatic state of this substance and the workforce involved in processing this substance. Extensive sensitivity and stability analyses of the core model revealed that the system is very resilient against perturbations and compensates for specific types of stress that real colonies face in their ecosystems. The core regulation system is highly scalable, and due to its buffer function, it can filter noise and find a new equilibrium quickly after environmental (supply) or colony-state (demand) changes. The common stomach regulation system is an example of convergent evolution among the three different societies, and we predict that similar integral control regulation mechanisms have evolved frequently within natural complex systems.}, } @article {pmid30530661, year = {2018}, author = {Yu, H and Dalby, PA}, title = {Exploiting correlated molecular-dynamics networks to counteract enzyme activity-stability trade-off.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12192-E12200}, doi = {10.1073/pnas.1812204115}, pmid = {30530661}, issn = {1091-6490}, abstract = {The directed evolution of enzymes for improved activity or substrate specificity commonly leads to a trade-off in stability. We have identified an activity-stability trade-off and a loss in unfolding cooperativity for a variant (3M) of Escherichia coli transketolase (TK) engineered to accept aromatic substrates. Molecular dynamics simulations of 3M revealed increased flexibility in several interconnected active-site regions that also form part of the dimer interface. Mutating the newly flexible active-site residues to regain stability risked losing the new activity. We hypothesized that stabilizing mutations could be targeted to residues outside of the active site, whose dynamics were correlated with the newly flexible active-site residues. We previously stabilized WT TK by targeting mutations to highly flexible regions. These regions were much less flexible in 3M and would not have been selected a priori as targets using the same strategy based on flexibility alone. However, their dynamics were highly correlated with the newly flexible active-site regions of 3M. Introducing the previous mutations into 3M reestablished the WT level of stability and unfolding cooperativity, giving a 10.8-fold improved half-life at 55 °C, and increased midpoint and aggregation onset temperatures by 3 °C and 4.3 °C, respectively. Even the activity toward aromatic aldehydes increased up to threefold. Molecular dynamics simulations confirmed that the mutations rigidified the active-site via the correlated network. This work provides insights into the impact of rigidifying mutations within highly correlated dynamic networks that could also be useful for developing improved computational protein engineering strategies.}, } @article {pmid30530660, year = {2019}, author = {Wintle, BA and Kujala, H and Whitehead, A and Cameron, A and Veloz, S and Kukkala, A and Moilanen, A and Gordon, A and Lentini, PE and Cadenhead, NCR and Bekessy, SA}, title = {Global synthesis of conservation studies reveals the importance of small habitat patches for biodiversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {909-914}, doi = {10.1073/pnas.1813051115}, pmid = {30530660}, issn = {1091-6490}, abstract = {Island biogeography theory posits that species richness increases with island size and decreases with isolation. This logic underpins much conservation policy and regulation, with preference given to conserving large, highly connected areas, and relative ambivalence shown toward protecting small, isolated habitat patches. We undertook a global synthesis of the relationship between the conservation value of habitat patches and their size and isolation, based on 31 systematic conservation planning studies across four continents. We found that small, isolated patches are inordinately important for biodiversity conservation. Our results provide a powerful argument for redressing the neglect of small, isolated habitat patches, for urgently prioritizing their restoration, and for avoiding simplistic application of island biogeography theory in conservation decisions.}, } @article {pmid30530656, year = {2018}, author = {Vallée, J}, title = {Urban isolation and daytime neighborhood social composition from Twitter data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11886-E11887}, doi = {10.1073/pnas.1816937115}, pmid = {30530656}, issn = {1091-6490}, mesh = {Cities ; Humans ; *Residence Characteristics ; *Urban Population ; }, } @article {pmid30530655, year = {2018}, author = {Wang, Q and Phillips, NE and Small, ML and Sampson, RJ}, title = {Reply to Vallée: Different questions for different data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11888-E11889}, doi = {10.1073/pnas.1818606115}, pmid = {30530655}, issn = {1091-6490}, mesh = {Cities ; *Residence Characteristics ; }, } @article {pmid30530654, year = {2018}, author = {Kaplonek, P and Khan, N and Reppe, K and Schumann, B and Emmadi, M and Lisboa, MP and Xu, FF and Calow, ADJ and Parameswarappa, SG and Witzenrath, M and Pereira, CL and Seeberger, PH}, title = {Improving vaccines against Streptococcus pneumoniae using synthetic glycans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13353-13358}, doi = {10.1073/pnas.1811862115}, pmid = {30530654}, issn = {1091-6490}, abstract = {Streptococcus pneumoniae remains a deadly disease in small children and the elderly even though conjugate and polysaccharide vaccines based on isolated capsular polysaccharides (CPS) are successful. The most common serotypes that cause infection are used in vaccines around the world, but differences in geographic and demographic serotype distribution compromises protection by leading vaccines. The medicinal chemistry approach to glycoconjugate vaccine development has helped to improve the stability and immunogenicity of synthetic vaccine candidates for several serotypes leading to the induction of higher levels of specific protective antibodies. Here, we show that marketed CPS-based glycoconjugate vaccines can be improved by adding synthetic glycoconjugates representing serotypes that are not covered by existing vaccines. Combination (coformulation) of synthetic glycoconjugates with the licensed vaccines Prevnar13 (13-valent) and Synflorix (10-valent) yields improved 15- and 13-valent conjugate vaccines, respectively, in rabbits. A pentavalent semisynthetic glycoconjugate vaccine containing five serotype antigens (sPCV5) elicits antibodies with strong in vitro opsonophagocytic activity. This study illustrates that synthetic oligosaccharides can be used in coformulation with both isolated polysaccharide glycoconjugates to expand protection from existing vaccines and each other to produce precisely defined multivalent conjugated vaccines.}, } @article {pmid30530653, year = {2018}, author = {Busoms, S and Paajanen, P and Marburger, S and Bray, S and Huang, XY and Poschenrieder, C and Yant, L and Salt, DE}, title = {Fluctuating selection on migrant adaptive sodium transporter alleles in coastal Arabidopsis thaliana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12443-E12452}, doi = {10.1073/pnas.1816964115}, pmid = {30530653}, issn = {1091-6490}, abstract = {Stressors such as soil salinity and dehydration are major constraints on plant growth, causing worldwide crop losses. Compounding these insults, increasing climate volatility requires adaptation to fluctuating conditions. Salinity stress responses are relatively well understood in Arabidopsis thaliana, making this system suited for the rapid molecular dissection of evolutionary mechanisms. In a large-scale genomic analysis of Catalonian A. thaliana, we resequenced 77 individuals from multiple salinity gradients along the coast and integrated these data with 1,135 worldwide A. thaliana genomes for a detailed understanding of the demographic and evolutionary dynamics of naturally evolved salinity tolerance. This revealed that Catalonian varieties adapted to highly fluctuating soil salinity are not Iberian relicts but instead have immigrated to this region more recently. De novo genome assembly of three allelic variants of the high-affinity K+ transporter (HKT1;1) locus resolved structural variation between functionally distinct alleles undergoing fluctuating selection in response to seasonal changes in soil salinity. Plants harboring alleles responsible for low root expression of HKT1;1 and consequently high leaf sodium (HKT1;1HLS) were migrants that have moved specifically into areas where soil sodium levels fluctuate widely due to geography and rainfall variation. We demonstrate that the proportion of plants harboring HKT1;1HLS alleles correlates with soil sodium level over time, HKT1;1HLS -harboring plants are better adapted to intermediate levels of salinity, and the HKT1;1HLS allele clusters with high-sodium accumulator accessions worldwide. Together, our evidence suggests that HKT1;1 is under fluctuating selection in response to climate volatility and is a worldwide determinant in adaptation to saline conditions.}, } @article {pmid30530652, year = {2018}, author = {Al-Bassam, J and Nithianantham, S}, title = {Malleable folding of coiled-coils regulates kinesin-3 dimerization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12845-12847}, doi = {10.1073/pnas.1818758115}, pmid = {30530652}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; *Dimerization ; *Kinesin ; Protein Domains ; Protein Folding ; }, } @article {pmid30530651, year = {2018}, author = {Henson, BM and Shin, DK and Thomas, KF and Ross, JA and Hush, MR and Hodgman, SS and Truscott, AG}, title = {Approaching the adiabatic timescale with machine learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13216-13221}, doi = {10.1073/pnas.1811501115}, pmid = {30530651}, issn = {1091-6490}, abstract = {The control and manipulation of quantum systems without excitation are challenging, due to the complexities in fully modeling such systems accurately and the difficulties in controlling these inherently fragile systems experimentally. For example, while protocols to decompress Bose-Einstein condensates (BECs) faster than the adiabatic timescale (without excitation or loss) have been well developed theoretically, experimental implementations of these protocols have yet to reach speeds faster than the adiabatic timescale. In this work, we experimentally demonstrate an alternative approach based on a machine-learning algorithm which makes progress toward this goal. The algorithm is given control of the coupled decompression and transport of a metastable helium condensate, with its performance determined after each experimental iteration by measuring the excitations of the resultant BEC. After each iteration the algorithm adjusts its internal model of the system to create an improved control output for the next iteration. Given sufficient control over the decompression, the algorithm converges to a solution that sets the current speed record in relation to the adiabatic timescale, beating out other experimental realizations based on theoretical approaches. This method presents a feasible approach for implementing fast-state preparations or transformations in other quantum systems, without requiring a solution to a theoretical model of the system. Implications for fundamental physics and cooling are discussed.}, } @article {pmid30530650, year = {2018}, author = {Kozuch, DJ and Stillinger, FH and Debenedetti, PG}, title = {Combined molecular dynamics and neural network method for predicting protein antifreeze activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13252-13257}, doi = {10.1073/pnas.1814945115}, pmid = {30530650}, issn = {1091-6490}, abstract = {Antifreeze proteins (AFPs) are a diverse class of proteins that depress the kinetically observable freezing point of water. AFPs have been of scientific interest for decades, but the lack of an accurate model for predicting AFP activity has hindered the logical design of novel antifreeze systems. To address this, we perform molecular dynamics simulation for a collection of well-studied AFPs. By analyzing both the dynamic behavior of water near the protein surface and the geometric structure of the protein, we introduce a method that automatically detects the ice binding face of AFPs. From these data, we construct a simple neural network that is capable of quantitatively predicting experimentally observed thermal hysteresis from a trio of relevant physical variables. The model's accuracy is tested against data for 17 known AFPs and 5 non-AFP controls.}, } @article {pmid30530649, year = {2018}, author = {Brown, AS and Meera, P and Altindag, B and Chopra, R and Perkins, EM and Paul, S and Scoles, DR and Tarapore, E and Magri, J and Huang, H and Jackson, M and Shakkottai, VG and Otis, TS and Pulst, SM and Atwood, SX and Oro, AE}, title = {MTSS1/Src family kinase dysregulation underlies multiple inherited ataxias.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12407-E12416}, doi = {10.1073/pnas.1816177115}, pmid = {30530649}, issn = {1091-6490}, abstract = {The genetically heterogeneous spinocerebellar ataxias (SCAs) are caused by Purkinje neuron dysfunction and degeneration, but their underlying pathological mechanisms remain elusive. The Src family of nonreceptor tyrosine kinases (SFK) are essential for nervous system homeostasis and are increasingly implicated in degenerative disease. Here we reveal that the SFK suppressor Missing-in-metastasis (MTSS1) is an ataxia locus that links multiple SCAs. MTSS1 loss results in increased SFK activity, reduced Purkinje neuron arborization, and low basal firing rates, followed by cell death. Surprisingly, mouse models for SCA1, SCA2, and SCA5 show elevated SFK activity, with SCA1 and SCA2 displaying dramatically reduced MTSS1 protein levels through reduced gene expression and protein translation, respectively. Treatment of each SCA model with a clinically approved Src inhibitor corrects Purkinje neuron basal firing and delays ataxia progression in MTSS1 mutants. Our results identify a common SCA therapeutic target and demonstrate a key role for MTSS1/SFK in Purkinje neuron survival and ataxia progression.}, } @article {pmid30530648, year = {2018}, author = {Zanini, F and Robinson, ML and Croote, D and Sahoo, MK and Sanz, AM and Ortiz-Lasso, E and Albornoz, LL and Rosso, F and Montoya, JG and Goo, L and Pinsky, BA and Quake, SR and Einav, S}, title = {Virus-inclusive single-cell RNA sequencing reveals the molecular signature of progression to severe dengue.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12363-E12369}, doi = {10.1073/pnas.1813819115}, pmid = {30530648}, issn = {1091-6490}, abstract = {Dengue virus (DENV) infection can result in severe complications. However, the understanding of the molecular correlates of severity is limited, partly due to difficulties in defining the peripheral blood mononuclear cells (PBMCs) that contain DENV RNA in vivo. Accordingly, there are currently no biomarkers predictive of progression to severe dengue (SD). Bulk transcriptomics data are difficult to interpret because blood consists of multiple cell types that may react differently to infection. Here, we applied virus-inclusive single-cell RNA-seq approach (viscRNA-Seq) to profile transcriptomes of thousands of single PBMCs derived early in the course of disease from six dengue patients and four healthy controls and to characterize distinct leukocyte subtypes that harbor viral RNA (vRNA). Multiple IFN response genes, particularly MX2 in naive B cells and CD163 in CD14+ CD16+ monocytes, were up-regulated in a cell-specific manner before progression to SD. The majority of vRNA-containing cells in the blood of two patients who progressed to SD were naive IgM B cells expressing the CD69 and CXCR4 receptors and various antiviral genes, followed by monocytes. Bystander, non-vRNA-containing B cells also demonstrated immune activation, and IgG1 plasmablasts from two patients exhibited clonal expansions. Lastly, assembly of the DENV genome sequence revealed diversity at unexpected sites. This study presents a multifaceted molecular elucidation of natural dengue infection in humans with implications for any tissue and viral infection and proposes candidate biomarkers for prediction of SD.}, } @article {pmid30530647, year = {2018}, author = {Chanderraj, R and Dickson, RP}, title = {Rethinking pneumonia: A paradigm shift with practical utility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13148-13150}, doi = {10.1073/pnas.1819024116}, pmid = {30530647}, issn = {1091-6490}, support = {K23 HL130641/HL/NHLBI NIH HHS/United States ; R21 AI137669/AI/NIAID NIH HHS/United States ; }, } @article {pmid30530646, year = {2018}, author = {Dixon, G and Liao, Y and Bay, LK and Matz, MV}, title = {Role of gene body methylation in acclimatization and adaptation in a basal metazoan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13342-13346}, doi = {10.1073/pnas.1813749115}, pmid = {30530646}, issn = {1091-6490}, abstract = {Gene body methylation (GBM) has been hypothesized to modulate responses to environmental change, including transgenerational plasticity, but the evidence thus far has been lacking. Here we show that coral fragments reciprocally transplanted between two distant reefs respond predominantly by increase or decrease in genome-wide GBM disparity: The range of methylation levels between lowly and highly methylated genes becomes either wider or narrower. Remarkably, at a broad functional level this simple adjustment correlated very well with gene expression change, reflecting a shifting balance between expressions of environmentally responsive and housekeeping genes. In our experiment, corals in a lower-quality habitat up-regulated genes involved in environmental responses, while corals in a higher-quality habitat invested more in housekeeping genes. Transplanted fragments showing closer GBM match to local corals attained higher fitness characteristics, which supports GBM's role in acclimatization. Fixed differences in GBM between populations did not align with plastic GBM changes and were mostly observed in genes with elevated FST, which suggests that they arose predominantly through genetic divergence. However, we cannot completely rule out transgenerational inheritance of acquired GBM states.}, } @article {pmid30530645, year = {2018}, author = {Kretzschmar, K and Post, Y and Bannier-Hélaouët, M and Mattiotti, A and Drost, J and Basak, O and Li, VSW and van den Born, M and Gunst, QD and Versteeg, D and Kooijman, L and van der Elst, S and van Es, JH and van Rooij, E and van den Hoff, MJB and Clevers, H}, title = {Profiling proliferative cells and their progeny in damaged murine hearts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12245-E12254}, doi = {10.1073/pnas.1805829115}, pmid = {30530645}, issn = {1091-6490}, abstract = {The significance of cardiac stem cell (CSC) populations for cardiac regeneration remains disputed. Here, we apply the most direct definition of stem cell function (the ability to replace lost tissue through cell division) to interrogate the existence of CSCs. By single-cell mRNA sequencing and genetic lineage tracing using two Ki67 knockin mouse models, we map all proliferating cells and their progeny in homoeostatic and regenerating murine hearts. Cycling cardiomyocytes were only robustly observed in the early postnatal growth phase, while cycling cells in homoeostatic and damaged adult myocardium represented various noncardiomyocyte cell types. Proliferative postdamage fibroblasts expressing follistatin-like protein 1 (FSTL1) closely resemble neonatal cardiac fibroblasts and form the fibrotic scar. Genetic deletion of Fstl1 in cardiac fibroblasts results in postdamage cardiac rupture. We find no evidence for the existence of a quiescent CSC population, for transdifferentiation of other cell types toward cardiomyocytes, or for proliferation of significant numbers of cardiomyocytes in response to cardiac injury.}, } @article {pmid30530175, year = {2018}, author = {Good, BH and Hallatschek, O}, title = {Effective models and the search for quantitative principles in microbial evolution.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {203-212}, doi = {10.1016/j.mib.2018.11.005}, pmid = {30530175}, issn = {1879-0364}, abstract = {Microbes evolve rapidly. Yet they do so in idiosyncratic ways, which depend on the specific mutations that are beneficial or deleterious in a given situation. At the same time, some population-level patterns of adaptation are strikingly similar across different microbial systems, suggesting that there may also be simple, quantitative principles that unite these diverse scenarios. We review the search for simple principles in microbial evolution, ranging from the biophysical level to emergent evolutionary dynamics. A key theme has been the use of effective models, which coarse-grain over molecular and cellular details to obtain a simpler description in terms of a few effective parameters. Collectively, these theoretical approaches provide a set of quantitative principles that facilitate understanding, prediction, and potentially control of evolutionary phenomena, though formidable challenges remain due to the ecological complexity of natural populations.}, } @article {pmid30530037, year = {2018}, author = {Lensmire, JM and Hammer, ND}, title = {Nutrient sulfur acquisition strategies employed by bacterial pathogens.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {52-58}, doi = {10.1016/j.mib.2018.11.002}, pmid = {30530037}, issn = {1879-0364}, abstract = {Pathogens have evolved elegant mechanisms to acquire essential nutrients from host environments. Sulfur is a requirement for bacterial growth and inorganic and organic sulfur-containing metabolites are abundant within the host-pathogen interface. A growing body of evidence suggests that pathogens are capable of scavenging both types of sulfur sources to fulfill the nutritional requirement. While therapeutic strategies focusing on inhibiting inorganic sulfate assimilation and cysteine synthesis show promise in vitro, in vivo efficacy maybe limited due to the diversity of host-derived sulfur sources and the fact that most pathogens are capable of acquiring multiple sources of sulfur.}, } @article {pmid30529253, year = {2019}, author = {Jex, AR and Gasser, RB and Schwarz, EM}, title = {Transcriptomic Resources for Parasitic Nematodes of Veterinary Importance.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {72-84}, doi = {10.1016/j.pt.2018.09.010}, pmid = {30529253}, issn = {1471-5007}, abstract = {Parasitic nematodes are important pathogens of animals, causing diseases that impact on agricultural production worldwide. Research on these worms has been constrained by a lack of genetic and genomic tools. Nonetheless, over the past decade this field has made substantial advances, many of which have been led by transcriptomic sequencing. The present review summarises major transcriptomic studies of veterinary parasitic nematodes in recent years, and comments on overarching themes stemming from this work that inform our understanding of parasitism. Finally, we comment on current, state-of-the-art informatic tools for the analysis of complex worm transcriptomes to extract maximum the molecular information from them.}, } @article {pmid30529252, year = {2019}, author = {Sullivan, CH and Majumdar, HD and Neilson, KM and Moody, SA}, title = {Six1 and Irx1 have reciprocal interactions during cranial placode and otic vesicle formation.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {68-79}, doi = {10.1016/j.ydbio.2018.12.003}, pmid = {30529252}, issn = {1095-564X}, support = {R01 DE022065/DE/NIDCR NIH HHS/United States ; R01 DE026434/DE/NIDCR NIH HHS/United States ; }, abstract = {The specialized sensory organs of the vertebrate head are derived from thickened patches of cells in the ectoderm called cranial sensory placodes. The developmental program that generates these placodes and the genes that are expressed during the process have been studied extensively in a number of animals, yet very little is known about how these genes regulate one another. We previously found via a microarray screen that Six1, a known transcriptional regulator of cranial placode fate, up-regulates Irx1 in ectodermal explants. In this study, we investigated the transcriptional relationship between Six1 and Irx1 and found that they reciprocally regulate each other throughout cranial placode and otic vesicle formation. Although Irx1 expression precedes that of Six1 in the neural border zone, its continued and appropriately patterned expression in the pre-placodal region (PPR) and otic vesicle requires Six1. At early PPR stages, Six1 expands the Irx1 domain, but this activity subsides over time and changes to a predominantly repressive effect. Likewise, Irx1 initially expands Six1 expression in the PPR, but later represses it. We also found that Irx1 and Sox11, a known direct target of Six1, reciprocally affect each other. This work demonstrates that the interactions between Six1 and Irx1 are continuous during PPR and placode development and their transcriptional effects on one another change over developmental time.}, } @article {pmid30529251, year = {2019}, author = {An, Y and Sekinaka, T and Tando, Y and Okamura, D and Tanaka, K and Ito-Matsuoka, Y and Takehara, A and Yaegashi, N and Matsui, Y}, title = {Derivation of pluripotent stem cells from nascent undifferentiated teratoma.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {43-55}, doi = {10.1016/j.ydbio.2018.11.020}, pmid = {30529251}, issn = {1095-564X}, abstract = {Teratomas are tumors consisting of components of the three germ layers that differentiate from pluripotent stem cells derived from germ cells. In the normal mouse testis, teratomas rarely form, but a deficiency in Dead-end1 (Dnd1) in mice with a 129/Sv genetic background greatly enhances teratoma formation. Thus, DND1 is crucial for suppression of teratoma development from germ cells. In the Dnd1 mutant testis, nascent teratoma cells emerge at E15.5. To understand the nature of early teratoma cells, we established cell lines in the presence of serum and leukemia inhibitory factor (LIF) from teratoma-forming cells in neonatal Dnd1 mutant testis. These cells, which we designated cultured Dnd1 mutant germ cells (CDGCs), were morphologically similar to embryonic stem cells (ESCs) and could be maintained in the naïve pluripotent condition. In addition, the cells expressed pluripotency genes including Oct4, Nanog, and Sox2; differentiated into cells of the three germ layers in culture; and contributed to chimeric mice. The expression levels of pluripotency genes and global transcriptomes in CDGCs as well as these cells' adaption to culture conditions for primed pluripotency suggested that their pluripotent status is intermediate between naïve and primed pluripotency. In addition, the teratoma-forming cells in the neonatal testis from which CDGCs were derived also showed gene expression profiles intermediate between naïve and primed pluripotency. The results suggested that germ cells in embryonic testes of Dnd1 mutants acquire the intermediate pluripotent status during the course of conversion into teratoma cells.}, } @article {pmid30529250, year = {2018}, author = {Li, J and Kim, T and Szymanski, DB}, title = {Multi-scale regulation of cell branching: Modeling morphogenesis.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.004}, pmid = {30529250}, issn = {1095-564X}, abstract = {Plant growth and development are driven by extended phases of irreversible cell expansion generating cells that increase in volume from 10- to 100-fold. Some specialized cell types define cortical sites that reinitiate polarized growth and generate branched cell morphology. This structural specialization of individual cells has a major importance for plant adaptation to diverse environments and practical importance in agricultural contexts. The patterns of cell shape are defined by highly integrated cytoskeletal and cell wall systems. Microtubules and actin filaments locally define the material properties of a tough outer cell wall to generate complex shapes. Forward genetics, powerful live cell imaging experiments, and computational modeling have provided insights into understanding of mechanisms of cell shape control. In particular, finite element modeling of the cell wall provides a new way to discover which cell wall heterogeneities generate complex cell shapes, and how cell shape and cell wall stress can feedback on the cytoskeleton to maintain growth patterns. This review focuses on cytoskeleton-dependent cell wall patterning during cell branching, and how combinations of multi-scale imaging experiments and computational modeling are being used to unravel systems-level control of morphogenesis.}, } @article {pmid30529233, year = {2018}, author = {Best, BT}, title = {Single-cell branching morphogenesis in the Drosophila trachea.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.12.001}, pmid = {30529233}, issn = {1095-564X}, abstract = {The terminal cells of the tracheal epithelium in Drosophila melanogaster are one of the few known cell types that undergo subcellular morphogenesis to achieve a stable, branched shape. During the animal's larval stages, the cells repeatedly sprout new cytoplasmic processes. These grow very long, wrapping around target tissues to which the terminal cells adhere, and are hollowed by a gas-filled subcellular tube for oxygen delivery. Our understanding of this ramification process remains rudimentary. This review aims to provide a comprehensive summary of studies on terminal cells to date, and attempts to extrapolate how terminal branches might be formed based on the known genetic and molecular components. Next to this cell-intrinsic branching mechanism, we examine the extrinsic regulation of terminal branching by the target tissue and the animal's environment. Finally, we assess the degree of similarity between the patterns established by the branching programs of terminal cells and other branched cells and tissues from a mathematical and conceptual point of view.}, } @article {pmid30529058, year = {2019}, author = {Hamid, R and Hajirnis, N and Kushwaha, S and Saleem, S and Kumar, V and Mishra, RK}, title = {Drosophila Choline transporter non-canonically regulates pupal eclosion and NMJ integrity through a neuronal subset of mushroom body.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {80-93}, doi = {10.1016/j.ydbio.2018.12.006}, pmid = {30529058}, issn = {1095-564X}, abstract = {Insect mushroom bodies (MB) have an ensemble of synaptic connections well-studied for their role in experience-dependent learning and several higher cognitive functions. MB requires neurotransmission for an efficient flow of information across synapses with different flexibility to meet the demand of the dynamically changing environment of an insect. Neurotransmitter transporters coordinate appropriate changes for an efficient neurotransmission at the synapse. Till date, there is no transporter reported for any of the previously known neurotransmitters in the intrinsic neurons of MB. In this study, we report a highly enriched expression of Choline Transporter (ChT) in Drosophila MB. We demonstrate that knockdown of ChT in a sub-type of MB neurons called α/β core (α/βc) and ϒ neurons leads to eclosion failure, peristaltic defect in larvae, and altered NMJ phenotype. These defects were neither observed on knockdown of proteins of the cholinergic locus in α/βc and ϒ neurons nor by knockdown of ChT in cholinergic neurons. Thus, our study provides insights into non-canonical roles of ChT in MB.}, } @article {pmid30529057, year = {2019}, author = {Zhang, D and Rollo, BN and Nagy, N and Stamp, L and Newgreen, DF}, title = {The enteric neural crest progressively loses capacity to form enteric nervous system.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {34-42}, doi = {10.1016/j.ydbio.2018.11.017}, pmid = {30529057}, issn = {1095-564X}, abstract = {Cells of the vagal neural crest (NC) form most of the enteric nervous system (ENS) by a colonising wave in the embryonic gut, with high cell proliferation and differentiation. Enteric neuropathies have an ENS deficit and cell replacement has been suggested as therapy. This would be performed post-natally, which raises the question of whether the ENS cell population retains its initial ENS-forming potential with age. We tested this on the avian model in organ culture in vitro (3 days) using recipient aneural chick midgut/hindgut combined with ENS-donor quail midgut or hindgut of ages QE5 to QE10. ENS cells from young donor tissues (≤ QE6) avidly colonised the aneural recipient, but this capacity dropped rapidly 2-3 days after the transit of the ENS cell wavefront. This loss in capability was autonomous to the ENS population since a similar decline was observed in ENS cells isolated by HNK1 FACS. Using QE5, 6, 8 and 10 midgut donors and extending the time of assay to 8 days in chorio-allantoic membrane grafts did not produce 'catch up' colonisation. NC-derived cells were counted in dissociated quail embryo gut and in transverse sections of chick embryo gut using NC, neuron and glial marker antibodies. This showed that the decline in ENS-forming ability correlated with a decrease in proportion of ENS cells lacking both neuronal and glial differentiation markers, but there were still large numbers of such cells even at stages with low colonisation ability. Moreover, ENS cells in small numbers from young donors were far superior in colonisation ability to larger numbers of apparently undifferentiated cells from older donors. This suggests that the decline of ENS-forming ability has both quantitative and qualitative aspects. In this case, ENS cells for cell therapies should aim to replicate the embryonic ENS stage rather than using post-natal ENS stem/progenitor cells.}, } @article {pmid30529028, year = {2018}, author = {Saurin, AJ and Delfini, MC and Maurel-Zaffran, C and Graba, Y}, title = {The Generic Facet of Hox Protein Function: (Trends in Genetics 34, 941-953, 2018).}, journal = {Trends in genetics : TIG}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tig.2018.11.006}, pmid = {30529028}, issn = {0168-9525}, } @article {pmid30529020, year = {2019}, author = {Robertson, RC and Manges, AR and Finlay, BB and Prendergast, AJ}, title = {The Human Microbiome and Child Growth - First 1000 Days and Beyond.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {131-147}, doi = {10.1016/j.tim.2018.09.008}, pmid = {30529020}, issn = {1878-4380}, abstract = {The assembly of microbial communities within the gastrointestinal tract during early life plays a critical role in immune, endocrine, metabolic, and other host developmental pathways. Environmental insults during this period, such as food insecurity and infections, can disrupt this optimal microbial succession, which may contribute to lifelong and intergenerational deficits in growth and development. Here, we review the human microbiome in the first 1000 days - referring to the period from conception to 2 years of age - and using a developmental model, we examine the role of early microbial succession in growth and development. We propose that an 'undernourished' microbiome is intergenerational, thereby perpetuating growth impairments into successive generations. We also identify and discuss the intertwining host-microbe-environment interactions occurring prenatally and during early infancy, which may impair the trajectories of healthy growth and development, and explore their potential as novel microbial targets for intervention.}, } @article {pmid30529007, year = {2018}, author = {Kenney, LJ}, title = {The role of acid stress in Salmonella pathogenesis.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {45-51}, doi = {10.1016/j.mib.2018.11.006}, pmid = {30529007}, issn = {1879-0364}, abstract = {After uptake by epithelial cells or engulfment by macrophages, Salmonella resides in an acidic vacuole. Salmonella senses this acidic compartment through the action of the EnvZ/OmpR two-component regulatory system. OmpR, in turn, represses the cadC/BA system, preventing neutralization of the bacterial cytoplasm. New, single cell techniques now enable us to observe that in response to acid stress, the pH is low in bacterial cells and acidification is critical for infection. Instead of recovering from acid stress, Salmonella uses acid pH as a signal to drive pathogenesis. The relevant molecular mechanisms employed by Salmonella to couple acid stress with the expression of virulence genes that promote intracellular survival are explored.}, } @article {pmid30528540, year = {2019}, author = {Ramos, EKS and Magalhães, RF and Marques, NCS and Baêta, D and Garcia, PCA and Santos, FR}, title = {Cryptic diversity in Brazilian endemic monkey frogs (Hylidae, Phyllomedusinae, Pithecopus) revealed by multispecies coalescent and integrative approaches.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {105-116}, doi = {10.1016/j.ympev.2018.11.022}, pmid = {30528540}, issn = {1095-9513}, abstract = {Even though Brazil is the world leader in amphibian diversity, a significant part of its richness remains unknown or hidden under cryptic taxa. Here, we used model-based species delimitation in an integrative taxonomic approach, by gathering molecular and morphometric data to assess cryptic taxa within the monkey frogs Pithecopus rohdei, from the Atlantic Forest, and P. megacephalus, from campos rupestres ecosystem. We sampled one mitochondrial, five nuclear loci, and 18 morphometric variables. Using species-delimitation methods with genetic and morphometric data, we recovered five divergent lineages within P. rohdei and no cryptic lineages were recovered for P. megacephalus. Morphometric data show differentiation only for one of the candidate species revealed by the delimitation approaches, suggesting that individuals from Doce River basin constitute a putative species for formal taxonomic description. The time-calibrated mtDNA tree shows that P. rohdei complex lineages began to diverge in late Miocene. However, dates from the multilocus species tree are more recent, occurring in Pleistocene, and suggesting their persistence in refuges of forest and sky islands within the Atlantic Forest biome. The existence of cryptic taxa within P. rohdei is, therefore, relevant for planning conservation strategies for this species complex in the Atlantic Forest biodiversity hotspot.}, } @article {pmid30528084, year = {2019}, author = {Przyboś, E and Rautian, M and Beliavskaia, A and Tarcz, S}, title = {Evaluation of the molecular variability and characteristics of Paramecium polycaryum and Paramecium nephridiatum, within subgenus Cypriostomum (Ciliophora, Protista).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {296-306}, doi = {10.1016/j.ympev.2018.12.003}, pmid = {30528084}, issn = {1095-9513}, abstract = {Although some Paramecium species are suitable research objects in many areas of life sciences, the biodiversity structure of other species is almost unknown. In the current survey, we present a molecular analysis of 60 Cypriostomum strains, which for the first time allows for the study of intra- and interspecific relationships within that subgenus, as well as the assessment of the biogeography patterns of its morphospecies. Analysis of COI mtDNA variation revealed three main clades (separated from each other by approximately 130 nucleotide substitutions), each one with internal sub-clusters (differing by 30 to 70 substitutions - a similar range found between P. aurelia cryptic species and P. bursaria syngens). The first clade is represented exclusively by P. polycaryum; the second one includes only four strains identified as P. calkinsi. The third cluster seems to be paraphyletic, as it includes P. nephridiatum, P. woodruffi, and Eucandidatus P. hungarianum. Some strains, previously identified as P. calkinsi, had COI sequences identical or very similar to P. nephridiatum ones. Morphological reinvestigation of several such strains revealed common morphological features with P. nephridiatum. The paper contains new information concerning speciation within particular species, i.e. existence of cryptic species within P. polycaryum (three) and in P. nephridiatum (six).}, } @article {pmid30528083, year = {2019}, author = {Thomaz, AT and Carvalho, TP and Malabarba, LR and Knowles, LL}, title = {Geographic distributions, phenotypes, and phylogenetic relationships of Phalloceros (Cyprinodontiformes: Poeciliidae): Insights about diversification among sympatric species pools.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {265-274}, doi = {10.1016/j.ympev.2018.12.008}, pmid = {30528083}, issn = {1095-9513}, abstract = {With 22 described species, Phalloceros is the most species-rich genus of Poeciliidae in South America. Phalloceros diversity is characterized by high degrees of endemism and sympatry in coastal and inland drainages in southeastern South America. The taxa are also characterized by pronounced differentiation in sexual characters (i.e., female urogenital papilla and male gonopodium), which might have contributed to their diversification. Here we estimate phylogenetic relationships based on more than 18,000 loci in 93 individuals representing 19 described species and two putative undescribed species. Morphologically defined species correspond to monophyletic species lineages, with individuals within a species clustering together in phylogenetic estimates, with the main exception being P. harpagos, supporting undiscovered diversity in this morphospecies. Shifts in the female and male sexual traits (i.e., urogenital papilla and gonopodium) occurred in concert multiple times along the phylogeny highlighting the role of sexual selection in driving divergence in this genus. Out of 22 valid species, 14 species are found in sympatry with at least one other species of this genus. However, most co-occurrences are observed among non-sister species suggesting that diversification among closely related species involved mostly allopatric speciation, with only two instances of sympatric sister-species observed. A strong mismatch in sexual traits among sympatric taxa suggests that co-existence may be linked to divergent sexual traits that maintain species genetic distinctiveness through mechanical disruptions of interbreeding.}, } @article {pmid30528082, year = {2019}, author = {Leduc, D and Zhao, ZQ}, title = {Phylogenetic position of the parasitic nematode Trophomera (Nematoda, Benthimermithidae): A molecular analysis.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {177-182}, doi = {10.1016/j.ympev.2018.12.005}, pmid = {30528082}, issn = {1095-9513}, abstract = {Benthimermithid nematodes are parasites of invertebrates currently classified within their own order. Relationships between the Benthimermithida and other nematode orders, however, remain unclear due to their relatively simple morphology, their rarity, and paucity of molecular sequence data. Here, we combine molecular sequences obtained from Trophomera cf. marionensis in the Kermadec Trench with existing Trophomera sequences to determine the phylogenetic position of benthimermithids. Our SSU analyses showed Trophomera to be most closely-related to the order Plectida, subclass Chromadorea. Trophomera sequences formed a well-supported monophyletic clade placed within the Plectida, however relationships with other taxa within the order could not be resolved. Based on the result of these analyses, we propose that the family Benthimermithidae be moved to the order Plectida, however, future research on the classification of the family should focus on the benthimermithid genera Bathynema and Adenodelphis, for which no molecular sequences are yet available. We could not confirm a relationship between Trophomera and the family Camacolaimidae, which are both characterised by the presence of a stylet or stylet-like structure in the buccal cavity. Stylets are a common feature of parasitic nematodes, and its presence in a free-living benthimermithid ancestor perhaps similar to present-day camacolaimids could have facilitated a transition to a parasitic lifestyle. Our SSU phylogenetic analyses show that some features of benthimermithids, including the trophosome and a parasitic life cycle where the adults mate outside the host, have evolved independently in different groups of parasitic nematodes.}, } @article {pmid30528081, year = {2019}, author = {Underwood, JN and Travers, MJ and Snow, M and Puotinen, M and Gouws, G}, title = {Cryptic lineages in the Wolf Cardinalfish living in sympatry on remote coral atolls.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {183-193}, doi = {10.1016/j.ympev.2018.12.001}, pmid = {30528081}, issn = {1095-9513}, abstract = {Coral reef health and biodiversity is under threat worldwide due to rapid climate change. However, much of the inter- and intra-specific diversity of coral reefs are undescribed even in well studied taxa such as fish. Delimiting previously unrecognised diversity is important for understanding the processes that generate and sustain biodiversity in coral reef ecosystems and informing strategies for their conservation and management. Many taxa that inhabit geographically isolated coral reefs rely on self-recruitment for population persistence, providing the opportunity for the evolution of unique genetic lineages through divergent selection and reproductive isolation. Many such lineages in corals and fish are morphologically similar or indistinguishable. Here, we report the discovery and characterisation of cryptic lineages of the Wolf Cardinalfish, Cheilodipterus artus, from the coral atolls of northwest Australia using multiple molecular markers from mitochondrial (CO1 and D-loop) and nuclear (microsatellites) DNA. Concordant results from all markers identified two highly divergent lineages that are morphologically cryptic and reproductively isolated. These lineages co-occurred at daytime resting sites, but the relative abundance of each lineage was strongly correlated with wave exposure. It appears, therefore, that fish from each lineage are better adapted to different microhabitats. Such cryptic and ecologically based diversity appears to be common in these atolls and may well aid resilience of these systems. Our results also highlight that underwater surveys based on visual identification clearly underestimate biodiversity, and that a taxonomic revision of the Cheilodipterus genus is necessary.}, } @article {pmid30528080, year = {2019}, author = {Sanchez-Puerta, MV and Edera, A and Gandini, CL and Williams, AV and Howell, KA and Nevill, PG and Small, I}, title = {Genome-scale transfer of mitochondrial DNA from legume hosts to the holoparasite Lophophytum mirabile (Balanophoraceae).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {243-250}, doi = {10.1016/j.ympev.2018.12.006}, pmid = {30528080}, issn = {1095-9513}, abstract = {Angiosperm mitochondrial horizontal gene transfer (HGT) has been widely reported during the past decades. With a few exceptions, foreign sequences are mitochondrial genes or intronic regions from other plants, indicating that HGT has played a major role in shaping mitochondrial genome evolution. Host-parasite relationships are a valuable system to study this phenomenon due to the high frequency of HGT. In particular, the interaction between mimosoid legumes and holoparasites of the genus Lophophytum represents an outstanding opportunity to discern HGT events. The mitochondrial genome of the holoparasite L. mirabile has remarkable properties, the most extraordinary of which is the presence of 34 out of 43 mitochondrial protein genes acquired from its legume host, with the stunning replacement of up to 26 native homologs. However, the origin of the intergenic sequences that represent the majority (>90%) of the L. mirabile mtDNA remains largely unknown. The lack of mitochondrial sequences available from the donor angiosperm lineage (mimosoid legumes) precluded a large-scale evolutionary study. We sequenced and assembled the mitochondrial genome of the mimosoid Acacia ligulata and performed genome wide comparisons with L. mirabile. The A. ligulata mitochondrial genome is almost 700 kb in size, encoding 60 genes. About 60% of the L. mirabile mtDNA had greatest affinity to members of the family Fabaceae (∼49% to mimosoids in particular) with an average sequence identity of ∼96%, including genes but mostly intergenic regions. These findings strengthen the mitochondrial fusion compatibility model for angiosperm mitochondrion-to-mitochondrion HGT.}, } @article {pmid30527960, year = {2019}, author = {Barry, KE and Mommer, L and van Ruijven, J and Wirth, C and Wright, AJ and Bai, Y and Connolly, J and De Deyn, GB and de Kroon, H and Isbell, F and Milcu, A and Roscher, C and Scherer-Lorenzen, M and Schmid, B and Weigelt, A}, title = {The Future of Complementarity: Disentangling Causes from Consequences.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {2}, pages = {167-180}, doi = {10.1016/j.tree.2018.10.013}, pmid = {30527960}, issn = {1872-8383}, abstract = {Evidence suggests that biodiversity supports ecosystem functioning. Yet, the mechanisms driving this relationship remain unclear. Complementarity is one common explanation for these positive biodiversity-ecosystem functioning relationships. Yet, complementarity is often indirectly quantified as overperformance in mixture relative to monoculture (e.g., 'complementarity effect'). This overperformance is then attributed to the intuitive idea of complementarity or, more specifically, to species resource partitioning. Locally, however, several unassociated causes may drive this overperformance. Here, we differentiate complementarity into three types of species differences that may cause enhanced ecosystem functioning in more diverse ecosystems: (i) resource partitioning, (ii) abiotic facilitation, and (iii) biotic feedbacks. We argue that disentangling these three causes is crucial for predicting the response of ecosystems to future biodiversity loss.}, } @article {pmid30527959, year = {2018}, author = {He, N and Liu, C and Piao, S and Sack, L and Xu, L and Luo, Y and He, J and Han, X and Zhou, G and Zhou, X and Lin, Y and Yu, Q and Liu, S and Sun, W and Niu, S and Li, S and Zhang, J and Yu, G}, title = {Ecosystem Traits Linking Functional Traits to Macroecology.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2018.11.004}, pmid = {30527959}, issn = {1872-8383}, abstract = {As the range of studies on macroecology and functional traits expands, integration of traits into higher-level approaches offers new opportunities to improve clarification of larger-scale patterns and their mechanisms and predictions using models. Here, we propose a framework for quantifying 'ecosystem traits' and means to address the challenges of broadening the applicability of functional traits to macroecology. Ecosystem traits are traits or quantitative characteristics of organisms (plants, animals, and microbes) at the community level expressed as the intensity (or density) normalized per unit land area. Ecosystem traits can inter-relate and integrate data from field trait surveys, eddy-flux observation, remote sensing, and ecological models, and thereby provide new resolution of the responses and feedback at regional to global scale.}, } @article {pmid30527795, year = {2019}, author = {Covas, R and Doutrelant, C}, title = {Testing the Sexual and Social Benefits of Cooperation in Animals.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {2}, pages = {112-120}, doi = {10.1016/j.tree.2018.11.006}, pmid = {30527795}, issn = {1872-8383}, abstract = {Theoretical models show that sexual and social selection can stabilise cooperation. However, field tests of these mechanisms have been difficult to conduct and the results are mixed. We discuss the conceptual and practical difficulties associated with testing the role of social and sexual selection on cooperation and argue that there are alternative ways of examining these hypotheses. Specifically, approaches based on the classic theories of sexual selection and signalling, and recent developments in the field of behavioural syndromes, provide mechanisms to insure the reliability of cooperation. In addition, methodological developments (social networks and microtracking) and long-term datasets, allow measuring partner choice in a cooperation context and the resulting fitness benefits for both the cooperators and the individuals that associate with them.}, } @article {pmid30527765, year = {2019}, author = {Mukherjee, AK and Sharma, S and Chowdhury, S}, title = {Non-duplex G-Quadruplex Structures Emerge as Mediators of Epigenetic Modifications.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {129-144}, doi = {10.1016/j.tig.2018.11.001}, pmid = {30527765}, issn = {0168-9525}, abstract = {The role of non-duplex DNA, the guanine-quadruplex structure in particular, is becoming widely appreciated. Increasing evidence in the last decade implicates quadruplexes in important processes such as transcription and replication. Interestingly, more recent work suggests roles for quadruplexes, in association with quadruplex-interacting proteins, in epigenetics through both DNA and histone modifications. Here, we review the effect of the quadruplex structure on post-replication epigenetic memory and quadruplex-induced promoter DNA/histone modifications. Furthermore, we highlight the epigenetic state of the telomerase promoter where quadruplexes could play a key regulatory role. Finally, we discuss the possibility that DNA structures such as quadruplexes, within a largely duplex DNA background, could act as molecular anchors for locally induced epigenetic modifications.}, } @article {pmid30527541, year = {2018}, author = {Welkie, DG and Rubin, BE and Diamond, S and Hood, RD and Savage, DF and Golden, SS}, title = {A Hard Day's Night: Cyanobacteria in Diel Cycles.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.11.002}, pmid = {30527541}, issn = {1878-4380}, support = {R35 GM118290/GM/NIGMS NIH HHS/United States ; }, abstract = {Cyanobacteria are photosynthetic prokaryotes that are influential in global geochemistry and are promising candidates for industrial applications. Because the livelihood of cyanobacteria is directly dependent upon light, a comprehensive understanding of metabolism in these organisms requires taking into account the effects of day-night transitions and circadian regulation. These events synchronize intracellular processes with the solar day. Accordingly, metabolism is controlled and structured differently in cyanobacteria than in heterotrophic bacteria. Thus, the approaches applied to engineering heterotrophic bacteria will need to be revised for the cyanobacterial chassis. Here, we summarize important findings related to diurnal metabolism in cyanobacteria and present open questions in the field.}, } @article {pmid30526688, year = {2018}, author = {Carrión, O and Larke-Mejía, NL and Gibson, L and Farhan Ul Haque, M and Ramiro-García, J and McGenity, TJ and Murrell, JC}, title = {Gene probing reveals the widespread distribution, diversity and abundance of isoprene-degrading bacteria in the environment.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {219}, pmid = {30526688}, issn = {2049-2618}, support = {694578-IsoMet//European Research Council/International ; NE/J009725/1//Natural Environment Research Council/ ; NE/J009555/1//Natural Environment Research Council/ ; No. 646, Colciencias/Newton Fund (2014)//Colciencias/ ; }, abstract = {BACKGROUND: Approximately 500 Tg of isoprene are emitted to the atmosphere annually, an amount similar to that of methane, and despite its significant effects on the climate, very little is known about the biological degradation of isoprene in the environment. Isolation and characterisation of isoprene degraders at the molecular level has allowed the development of probes targeting isoA encoding the α-subunit of the isoprene monooxygenase. This enzyme belongs to the soluble diiron centre monooxygenase family and catalyses the first step in the isoprene degradation pathway. The use of probes targeting key metabolic genes is a successful approach in molecular ecology to study specific groups of bacteria in complex environments. Here, we developed and tested a novel isoA PCR primer set to study the distribution, abundance, and diversity of isoprene degraders in a wide range of environments.

RESULTS: The new isoA probes specifically amplified isoA genes from taxonomically diverse isoprene-degrading bacteria including members of the genera Rhodococcus, Variovorax, and Sphingopyxis. There was no cross-reactivity with genes encoding related oxygenases from non-isoprene degraders. Sequencing of isoA amplicons from DNA extracted from environmental samples enriched with isoprene revealed that most environments tested harboured a considerable variety of isoA sequences, with poplar leaf enrichments containing more phylogenetically diverse isoA genes. Quantification by qPCR using these isoA probes revealed that isoprene degraders are widespread in the phyllosphere, terrestrial, freshwater and marine environments. Specifically, soils in the vicinity of high isoprene-emitting trees contained the highest number of isoprene-degrading bacteria.

CONCLUSION: This study provides the molecular ecology tools to broaden our knowledge of the distribution, abundance and diversity of isoprene degraders in the environment, which is a fundamental step necessary to assess the impact that microbes have in mitigating the effects of this important climate-active gas.}, } @article {pmid30526686, year = {2018}, author = {Belachew, A and Tewabe, T and Miskir, Y and Melese, E and Wubet, E and Alemu, S and Teshome, T and Minichel, Y and Tesfa, G}, title = {Prevalence and associated factors of hypertension among adult patients in Felege-Hiwot Comprehensive Referral Hospitals, northwest, Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {876}, pmid = {30526686}, issn = {1756-0500}, abstract = {OBJECTIVE: The main objective of this study was to assess the prevalence and factors associated with hypertension among adult patients in Felege-Hiwot Comprehensive Referral Hospital, northwest Ethiopia, 2018.

RESULT: The prevalence of hypertension in the current study area was 27.3%. Known history of cardiac problems [AOR = 6.9; 95% CI (1.24, 11.44)], alcohol consumption [AOR = 2.2; 95% CI (1.04, 5.05)], abdominal obesity [AOR = 2.3; 95% CI (1.02, 5.04)], and obesity [AOR = 4.8; 95% CI (1.12, 8.34)] were factors associated independently with hypertension.}, } @article {pmid30526683, year = {2018}, author = {Draper, LA and Ryan, FJ and Smith, MK and Jalanka, J and Mattila, E and Arkkila, PA and Ross, RP and Satokari, R and Hill, C}, title = {Long-term colonisation with donor bacteriophages following successful faecal microbial transplantation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {220}, pmid = {30526683}, issn = {2049-2618}, support = {SFI/12/RC/2273//Science Foundation Ireland/Ireland ; 258439//Academy of Finland/ ; 283088//Academy of Finland/ ; 304490//Academy of Finland/ ; }, abstract = {BACKGROUND: Faecal microbiota transplantation (FMT) is used in the treatment of recurrent Clostridium difficile infection. Its success is typically attributed to the restoration of a diverse microbiota. Viruses (including bacteriophages) are the most numerically dominant and potentially the most diverse members of the microbiota, but their fate following FMT has not been well studied.

RESULTS: We studied viral transfer following FMT from 3 donors to 14 patients. Recipient viromes resembled those of their donors for up to 12 months. Tracking individual bacteriophage colonisation revealed that engraftment of individual bacteriophages was dependent on specific donor-recipient pairings. Specifically, multiple recipients from a single donor displayed highly individualised virus colonisation patterns.

CONCLUSIONS: The impact of viruses on long-term microbial dynamics is a factor that should be reviewed when considering FMT as a therapeutic option.}, } @article {pmid30526656, year = {2018}, author = {Vilela, VS and da Silva, BRA and da Costa, CH and Lopes, AJ and Levy, RA and Rufino, R}, title = {Effects of treatment with rituximab on microcirculation in patients with long-term systemic sclerosis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {874}, pmid = {30526656}, issn = {1756-0500}, abstract = {OBJECTIVE: To investigate the effect of rituximab on microcirculation in long-term SSc.

RESULTS: Four patients with diffuse SSc over 3 years of disease received rituximab cycles of two 1-g infusions every 6 months for 2 years. Videocapillaroscopy was performed at baseline, 12 months, and 24 months and semi-quantitative scoring of videocapillaroscopy abnormalities was performed and the microangiopathy evolution score (MES: range 0-9) was calculated. The mean disease duration was 5 years (range 3-15). On videocapillaroscopy, giant capillaries and hemorrhages remained stable from baseline to 24 months. Capillary loss, abnormally-shaped capillaries, and MES stabilized at 12 months and increased by 24.5% and 28% at 24 months. Rituximab improves microcirculation in long-term SSc. Stabilization and reduced progression of microcirculation abnormalities were achieved at 12 and 24 months, respectively.}, } @article {pmid30526653, year = {2018}, author = {Kassem, Z and Burmeister, C and Johnson, DA and Dakki, H and Joseph, CLM and Cassidy-Bushrow, AE}, title = {Reliability of birth weight recall by parent or guardian respondents in a study of healthy adolescents.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {878}, pmid = {30526653}, issn = {1756-0500}, abstract = {OBJECTIVE: Birth weight, which can be an indicator for risk of chronic diseases throughout the lifespan, is one of the most commonly used measures in the study of developmental origins of health and disease. There is limited information on the reliability of parent/guardian reported birth weight by race or by respondent type (i.e., mother, father, other caregiver).

RESULTS: Birth weight was reported by a respondent for 309 of the 333 (92.8%) study participants; of these, chart obtained birth weight was available for 236 (76.4%). There was good agreement between respondent report and chart obtained birth weight. Over half (N = 145, 61.4%) of respondents reported a birth weight within ± 100 g of what was in the chart; 60.9% of black participants (n = 81) and 62.1% of white participants (n = 64) fell within 100 g. Overall, mothers were 3.31 (95% CI 1.18, 9.33) times more likely than fathers to correctly recall the child's birthweight within ± 100 g (p = 0.023). Respondent reported birth weight is a reliable alternative to chart obtained birth weight. Mothers were found to be most accurate in reporting birth weight of the child. Race/ethnicity was not significantly associated with reliability of birth weight reporting.}, } @article {pmid30526647, year = {2018}, author = {Gebrekristos, G and Teweldemedhin, M and Hagos, L and Gebrewahid, T and Gidey, B and Gebreyesus, H}, title = {Hepatitis C virus infections and associated risk factors in patients with diabetes mellitus; case control study in North West Tigray, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {873}, pmid = {30526647}, issn = {1756-0500}, abstract = {OBJECTIVE: The objective of this study was to determine the seroprevalence of Hepatitis C virus among patients with Diabetes mellitus and healthy control groups in North West Tigray. Blood samples from each study subject was tested for Hepatitis C virus by using anti Hepatitis C virus antibody rapid test kits and confirmed using enzyme linked immuno sorbent assy.

RESULT: The overall seroprevalence of Hepatitis C virus, Hepatitis C virus among diabetic and non diabetic study subjects were found (16.7, 28, and 6) % respectively. Multi varate logistic regression analysis result shows that study subject with uvulotomy, previous history of immunosuppressive disease, and study subjects with fast blood glucose (≥ 126 mg/dl) showed statistically significant association with anti Hepatitis C virus antibody sero status [AOR (12.4 (3.5-18.3); 0.1 (0.03-0.5); and 8.6 (1.7-13)] respectively.}, } @article {pmid30526644, year = {2018}, author = {Haftu, A and Hagos, H and Mehari, MA and G/Her, B}, title = {Pregnant women adherence level to antenatal care visit and its effect on perinatal outcome among mothers in Tigray Public Health institutions, 2017: cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {872}, pmid = {30526644}, issn = {1756-0500}, abstract = {OBJECTIVE: To assess pregnant women adherence level to antenatal care visit and its effect on perinatal outcome among mothers in Tigray Public Health institutions, 2017.

RESULTS: The overall adherence level of the women towards to antenatal care visit was 49.9% and incidence of PPH, still birth, early neonatal death, late neonatal death and low birth weight complication was 4.3%, 2.3%, 2.7%, 1.9% and 7.5% respectively. PPH, preterm labor, early neonatal death and LBW complication was reduced by 81.2%, 52%, 61% and 46% respectively among women's with complete adherence to ANC visit.}, } @article {pmid30526642, year = {2018}, author = {Mortensen, MA and Vilstrup, MH and Poulsen, MH and Gerke, O and Høilund-Carlsen, PF and Lund, L}, title = {A prospective study on dual time 18F-FDG-PET/CT in high-risk prostate cancer patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {871}, pmid = {30526642}, issn = {1756-0500}, support = {A8400//Kræftens Bekæmpelse/ ; }, abstract = {OBJECTIVE: This proof of concept study investigated whether dual time point FDG-PET/CT with image acquisition after 1 and 3 h could be useful in preoperative staging of patients undergoing robot-assisted radical prostatectomy and extended pelvic lymph node dissection for high-risk prostate cancer.

RESULTS: Twenty patients with high-risk prostate cancer underwent dual time point FDG-PET/CT before undergoing surgery. Histologically confirmed lymph node metastases were found in 9/20 (45%). A median of 19 (range 10-41; n = 434) lymph nodes were removed per patient. Pelvic lymph nodes with detectable FDG uptake were seen in two patients only, but the FDG-avid lesion on PET did not correspond with pathological findings in either patient. We found a significant increase in maximal standardized uptake value of the prostate of around 30% between early and late imaging. We found no correlation between clinical findings after radical prostatectomy and PET measurements.}, } @article {pmid30526641, year = {2018}, author = {Wemakor, A and Garti, H and Azongo, T and Garti, H and Atosona, A}, title = {Young maternal age is a risk factor for child undernutrition in Tamale Metropolis, Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {877}, pmid = {30526641}, issn = {1756-0500}, abstract = {OBJECTIVE: Malnutrition is a common cause of morbidity and mortality in children. The aim of this study was to compare the nutritional status of children under 5 years of teenage and adult mothers in Tamale Metropolis, Ghana. A case-control study involving 300 (150 cases, 150 controls) mother-child pairs was carried out. A questionnaire was used to collect data on socio-demographic characteristics of mothers and children and anthropometry was used to assess the nutritional status of children. Anthropometric z-scores derived based on WHO Child Growth Standards were used to determine stunting, wasting and underweight statuses of children. Logistic regression analysis was used to compare the nutritional status of children of teenage and adult mothers.

RESULTS: Children of teenage mothers, compared to those of adult mothers, were 8 times more likely to be stunted [Adjusted Odds Ratio (AOR) = 7.56; 95% confidence interval (CI) 4.20-13.63], 3 times more likely to be wasted (AOR = 2.90; 95% CI 1.04-8.04), and 13 times more likely to be underweight (AOR = 12.78; 95% CI 4.69-34.81) after adjusting for potential confounders. The risk of child malnutrition increases with young maternal age; interventions should be targeted at teenage mothers and their children to reduce the risk of malnutrition.}, } @article {pmid30526638, year = {2018}, author = {Muzondo, M and Shamu, A and Shambira, G and Gombe, NT and Juru, TP and Tshimanga, M}, title = {Evaluation of the acute flaccid paralysis (AFP) surveillance system in Mwenezi district, Masvingo, 2018: a descriptive study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {875}, pmid = {30526638}, issn = {1756-0500}, abstract = {OBJECTIVES: Poliomyelitis is an infectious disease caused by the polio virus which affects mostly young children below the age of 15 years. For surveillance children with acute flaccid paralysis (AFP) are tracked. In Zimbabwe every district should report two cases per 100,000 population of children under the age of 15 years old. In 2017, Mwenezi district failed to detect any AFP cases. We therefore evaluated the AFP surveillance system in Mwenezi district. We conducted a surveillance system evaluation using the updated Centers for Disease Control guidelines for evaluating public health surveillance systems. We interviewed health workers in Mwenezi district and looked at AFP records from January to December 2017.

RESULTS: The main reasons for failure to report a case in 2017 were the vastness of the district with bad road networks as well as lack of a dedicated vehicle to carry out EPI outreach activities. About a quarter, 24%, of the health workers did not know the specimen that is used in AFP diagnosis. The AFP surveillance system in Mwenezi district was performing poorly due to lack of active search of cases in the community caused by disruption of EPI outreach activities.}, } @article {pmid30526554, year = {2018}, author = {Keleher, MR and Zaidi, R and Hicks, L and Shah, S and Xing, X and Li, D and Wang, T and Cheverud, JM}, title = {A high-fat diet alters genome-wide DNA methylation and gene expression in SM/J mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {888}, pmid = {30526554}, issn = {1471-2164}, support = {#16PRE26420105//American Heart Association/ ; U01 HG009391/HG/NHGRI NIH HHS/United States ; R01 HG007175/HG/NHGRI NIH HHS/United States ; U01 CA200060/CA/NCI NIH HHS/United States ; # UL1TR000448//National Center for Research Resources/ ; R01 ES024992/ES/NIEHS NIH HHS/United States ; #P30 DK020579//Washington University in St. Louis/ ; P30 CA91842//National Cancer Institute/ ; R25 DA027995/DA/NIDA NIH HHS/United States ; U24 ES026699/ES/NIEHS NIH HHS/United States ; R01 HG007354/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: While the genetics of obesity has been well defined, the epigenetics of obesity is poorly understood. Here, we used a genome-wide approach to identify genes with differences in both DNA methylation and expression associated with a high-fat diet in mice.

RESULTS: We weaned genetically identical Small (SM/J) mice onto a high-fat or low-fat diet and measured their weights weekly, tested their glucose and insulin tolerance, assessed serum biomarkers, and weighed their organs at necropsy. We measured liver gene expression with RNA-seq (using 21 total libraries, each pooled with 2 mice of the same sex and diet) and DNA methylation with MRE-seq and MeDIP-seq (using 8 total libraries, each pooled with 4 mice of the same sex and diet). There were 4356 genes with expression differences associated with diet, with 184 genes exhibiting a sex-by-diet interaction. Dietary fat dysregulated several pathways, including those involved in cytokine-cytokine receptor interaction, chemokine signaling, and oxidative phosphorylation. Over 7000 genes had differentially methylated regions associated with diet, which occurred in regulatory regions more often than expected by chance. Only 5-10% of differentially methylated regions occurred in differentially expressed genes, however this was more often than expected by chance (p = 2.2 × 10- 8).

CONCLUSIONS: Discovering the gene expression and methylation changes associated with a high-fat diet can help to identify new targets for epigenetic therapies and inform about the physiological changes in obesity. Here, we identified numerous genes with altered expression and methylation that are promising candidates for further study.}, } @article {pmid30526526, year = {2018}, author = {Zhou, D and Liu, X and Gao, S and Guo, J and Su, Y and Ling, H and Wang, C and Li, Z and Xu, L and Que, Y}, title = {Foreign cry1Ac gene integration and endogenous borer stress-related genes synergistically improve insect resistance in sugarcane.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {342}, pmid = {30526526}, issn = {1471-2229}, support = {31701491//National Natural Science Foundation of China/ ; CARS-17//Sugar Crop Research System of China/ ; 2015NZ0002-2//Science and Technology Major Project of Fujian Province/ ; 2017.6.2//the open funding of National Engineering Research Center for Sugarcane, Fujian Agriculture and Forestry University/ ; 1122YB015//Scientific Research Foundation of Graduate School of Fujian Agriculture and Forestry University/ ; E51761//Doctoral Scientific Research Start-up Funding of Hunan University of Science and Technology/ ; }, mesh = {Animals ; Bacterial Proteins/*genetics ; Crop Production ; Endotoxins/*genetics ; Genes, Plant/*genetics ; Hemolysin Proteins/*genetics ; Herbivory ; Larva ; *Moths ; Plant Breeding/methods ; Plants, Genetically Modified ; Saccharum/*genetics/parasitology ; Stress, Physiological/genetics ; }, abstract = {BACKGROUND: Sugarcane (Saccharum spp. hybrids) is considered the most globally important sugar-producing crop and raw material for biofuel. Insect attack is a major issue in sugarcane cultivation, resulting in yield losses and sucrose content reductions. Stem borer (Diatraea saccharalis F.) causes serious yield losses in sugarcane worldwide. However, insect-resistant germplasms for sugarcane are not available in any collections all over the world, and the molecular mechanism of insect resistance has not been elucidated. In this study, cry1Ac transgenic sugarcane lines were obtained and the biological characteristics and transgene dosage effect were investigated and a global exploration of gene expression by transcriptome analysis was performed.

RESULTS: The transgene copies of foreign cry1Ac were variable and random. The correlation between the cry1Ac protein and cry1Ac gene copies differed between the transgenic lines from FN15 and ROC22. The medium copy lines from FN15 showed a significant linear relationship, while ROC22 showed no definite dosage effect. The transgenic lines with medium copies of cry1Ac showed an elite phenotype. Transcriptome analysis by RNA sequencing indicated that up/down regulated differentially expressed genes were abundant among the cry1Ac sugarcane lines and the receptor variety. Foreign cry1Ac gene and endogenous borer stress-related genes may have a synergistic effect. Three lines, namely, A1, A5, and A6, were selected for their excellent stem borer resistance and phenotypic traits and are expected to be used directly as cultivars or crossing parents for sugarcane borer resistance breeding.

CONCLUSIONS: Cry1Ac gene integration dramatically improved sugarcane insect resistance. The elite transgenic offspring contained medium transgene copies. Foreign cry1Ac gene integration and endogenous borer stress-related genes may have a synergistic effect on sugarcane insect resistance improvement.}, } @article {pmid30526508, year = {2018}, author = {Kraaijeveld, K and Oostra, V and Liefting, M and Wertheim, B and de Meijer, E and Ellers, J}, title = {Regulatory and sequence evolution in response to selection for improved associative learning ability in Nasonia vitripennis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {892}, pmid = {30526508}, issn = {1471-2164}, support = {VICI grant 865.12.003//NWO/ ; }, abstract = {BACKGROUND: Selection acts on the phenotype, yet only the genotype is inherited. While both the phenotypic and genotypic response to short-term selection can be measured, the link between these is a major unsolved problem in evolutionary biology, in particular for complex behavioural phenotypes.

RESULTS: Here we characterize the genomic and the transcriptomic basis of associative learning ability in the parasitic wasp Nasonia vitripennis and use gene network analysis to link the two. We artificially selected for improved associative learning ability in four independent pairs of lines and identified signatures of selection across the genome. Allele frequency diverged consistently between the selected and control lines in 118 single nucleotide polymorphisms (SNPs), clustering in 51 distinct genomic regions containing 128 genes. The majority of SNPs were found in regulatory regions, suggesting a potential role for gene expression evolution. We therefore sequenced the transcriptomes of selected and control lines and identified 36 consistently differentially expressed transcripts with large changes in expression. None of the differentially expressed genes also showed sequence divergence as a result of selection. Instead, gene network analysis showed many of the genes with consistent allele frequency differences and all of the differentially expressed genes to cluster in a single co-expression network. At a functional level, both genomic and transcriptomic analyses implicated members of gene networks known to be involved in neural plasticity and cognitive processes.

CONCLUSIONS: Taken together, our results reveal how specific cognitive abilities can readily respond to selection via a complex interplay between regulatory and sequence evolution.}, } @article {pmid30526500, year = {2018}, author = {Rusinov, IS and Ershova, AS and Karyagina, AS and Spirin, SA and Alexeevski, AV}, title = {Avoidance of recognition sites of restriction-modification systems is a widespread but not universal anti-restriction strategy of prokaryotic viruses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {885}, pmid = {30526500}, issn = {1471-2164}, support = {16-14-10319//Russian Science Foundation/ ; }, abstract = {BACKGROUND: Restriction-modification (R-M) systems protect bacteria and archaea from attacks by bacteriophages and archaeal viruses. An R-M system specifically recognizes short sites in foreign DNA and cleaves it, while such sites in the host DNA are protected by methylation. Prokaryotic viruses have developed a number of strategies to overcome this host defense. The simplest anti-restriction strategy is the elimination of recognition sites in the viral genome: no sites, no DNA cleavage. Even a decrease of the number of recognition sites can help a virus to overcome this type of host defense. Recognition site avoidance has been a known anti-restriction strategy of prokaryotic viruses for decades. However, recognition site avoidance has not been systematically studied with the currently available sequence data. We analyzed the complete genomes of almost 4000 prokaryotic viruses with known host species and more than 17,000 restriction endonucleases with known specificities in terms of recognition site avoidance.

RESULTS: We observed considerable limitations of recognition site avoidance as an anti-restriction strategy. Namely, the avoidance of recognition sites is specific for dsDNA and ssDNA prokaryotic viruses. Avoidance is much more pronounced in the genomes of non-temperate bacteriophages than in the genomes of temperate ones. Avoidance is not observed for the sites of Type I and Type IIG systems and is very rarely observed for the sites of Type III systems. The vast majority of avoidance cases concern recognition sites of orthodox Type II restriction-modification systems. Even under these constraints, complete or almost complete elimination of sites is observed for approximately one-tenth of viral genomes and a significant under-representation for approximately one-fourth of them.

CONCLUSIONS: Avoidance of recognition sites of restriction-modification systems is a widespread but not universal anti-restriction strategy of prokaryotic viruses.}, } @article {pmid30526499, year = {2018}, author = {De la Fuente Cantó, C and Russell, J and Hackett, CA and Booth, A and Dancey, S and George, TS and Waugh, R}, title = {Genetic dissection of quantitative and qualitative traits using a minimum set of barley Recombinant Chromosome Substitution Lines.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {340}, pmid = {30526499}, issn = {1471-2229}, support = {KBBE.2011.1.2-05//FP7-KBBE-2011-5/ ; }, mesh = {Cell Line ; Chromosome Mapping ; Chromosomes, Plant/*genetics ; Genetic Association Studies ; Genome, Plant/genetics ; Hordeum/*genetics ; Plant Breeding/methods ; Quantitative Trait Loci/*genetics ; Quantitative Trait, Heritable ; Recombination, Genetic/genetics ; }, abstract = {BACKGROUND: Exploring the natural occurring genetic variation of the wild barley genepool has become a major target of barley crop breeding programmes aiming to increase crop productivity and sustainability in global climate change scenarios. However this diversity remains unexploited and effective approaches are required to investigate the benefits that unadapted genomes could bring to crop improved resilience. In the present study, a set of Recombinant Chromosome Substitution Lines (RCSLs) derived from an elite barley cultivar 'Harrington' as the recurrent parent, and a wild barley accession from the Fertile Crescent 'Caesarea 26-24', as the donor parent (Matus et al. Genome 46:1010-23, 2003) have been utilised in field and controlled conditions to examine the contribution of wild barley genome as a source of novel allelic variation for the cultivated barley genepool.

METHODS: Twenty-eight RCSLs which were selected to represent the entire genome of the wild barley accession, were genotyped using the 9 K iSelect SNP markers (Comadran et al. Nat Genet 44:1388-92, 2012) and phenotyped for a range of morphological, developmental and agronomic traits in 2 years using a rain-out shelter with four replicates and three water treatments. Data were analysed for marker traits associations using a mixed model approach.

RESULTS: We identified lines that differ significantly from the elite parent for both qualitative and quantitative traits across growing seasons and water regimes. The detailed genotypic characterisation of the lines for over 1800 polymorphic SNP markers and the design of a mixed model analysis identified chromosomal regions associated with yield related traits where the wild barley allele had a positive response increasing grain weight and size. In addition, variation for qualitative characters, such as the presence of cuticle waxes on the developing spikes, was associated with the wild barley introgressions. Despite the coarse location of the QTLs, interesting candidate genes for the major marker-trait associations were identified using the recently released barley genome assembly.

CONCLUSION: This study has highlighted the role of exotic germplasm to contribute novel allelic variation by using an optimised experimental approach focused on an exotic genetic library. The results obtained constitute a step forward to the development of more tolerant and resilient varieties.}, } @article {pmid30526498, year = {2018}, author = {Yang, J and Zhang, Y and Wang, X and Wang, W and Li, Z and Wu, J and Wang, G and Wu, L and Zhang, G and Ma, Z}, title = {HyPRP1 performs a role in negatively regulating cotton resistance to V. dahliae via the thickening of cell walls and ROS accumulation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {339}, pmid = {30526498}, issn = {1471-2229}, support = {31301370//National Natural Science Foundation of China/ ; CARS18-08//Fund of the China Agriculture Research System/ ; 16226307D//Science and Technology Support Program of Hebei Province/ ; }, mesh = {Arabidopsis ; Cell Wall/*metabolism ; *Disease Resistance ; Gene Expression Profiling ; Gene Silencing ; Gossypium/immunology/*metabolism ; Plant Diseases/immunology/*microbiology ; Plant Proteins/*physiology ; Plants, Genetically Modified ; Reactive Oxygen Species/*metabolism ; Verticillium ; }, abstract = {BACKGROUND: Developing tolerant cultivars by incorporating resistant genes is regarded as a potential strategy for controlling Verticillium wilt that causes severe losses in the yield and fiber quality of cotton.

RESULTS: Here, we identified the gene GbHyPRP1 in Gossypium barbadense, which encodes a protein containing both proline-rich repetitive and Pollen Ole e I domains. GbHyPRP1 is located in the cell wall. The transcription of this gene mainly occurs in cotton roots and stems, and is drastically down-regulated upon infection with Verticillium dahliae. Silencing HyPRP1 dramatically enhanced cotton resistance to V. dahliae. Over-expression of HyPRP1 significantly compromised the resistance of transgenic Arabidopsis plants to V. dahliae. The GbHyPRP1 promoter region contained several putative phytohormone-responsive elements, of which SA was associated with gene down-regulation. We compared the mRNA expression patterns of HyPRP1-silenced plants and the control at the global level by RNA-Seq. A total of 1735 unique genes exhibited significant differential expression. Of these, 79 DEGs involved in cell wall biogenesis and 43 DEGs associated with the production of ROS were identified. Further, we observed a dramatic thickening of interfascicular fibers and vessel walls and an increase in lignin in the HyPRP1-silenced cotton plants compared with the control after inoculation with V. dahliae. Additionally, silencing of HyPRP1 markedly enhanced ROS accumulation in the root tips of cotton inoculated with V. dahliae.

CONCLUSIONS: Taken together, our results suggest that HyPRP1 performs a role in the negative regulation of cotton resistance to V. dahliae via the thickening of cell walls and ROS accumulation.}, } @article {pmid30526497, year = {2018}, author = {Luo, XW and Zhang, DY and Zhu, TH and Zhou, XG and Peng, J and Zhang, SB and Liu, Y}, title = {Adaptation mechanism and tolerance of Rhodopseudomonas palustris PSB-S under pyrazosulfuron-ethyl stress.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {207}, pmid = {30526497}, issn = {1471-2180}, support = {2017YFD0800702//the National Key R&D Program of China/ ; }, abstract = {BACKGROUND: Pyrazosulfuron-ethyl is a long lasting herbicide in the agro-ecosystem and its residue is toxic to crops and other non-target organisms. A better understanding of molecular basis in pyrazosulfuron-ethyl tolerant organisms will shed light on the adaptive mechanisms to this herbicide.

RESULTS: Pyrazosulfuron-ethyl inhibited biomass production in Rhodopseudomonas palustris PSB-S, altered cell morphology, suppressed flagella formation, and reduced pigment biosynthesis through significant suppression of carotenoids biosynthesis. A total of 1127 protein spots were detected in the two-dimensional gel electrophoresis. Among them, 72 spots representing 56 different proteins were found to be differently expressed using MALDI-TOF/TOF-MS, including 26 up- and 30 down-regulated proteins in the pyrazosulfuron-ethyl-treated PSB-S cells. The up-regulated proteins were involved predominantly in oxidative stress or energy generation pathways, while most of the down-regulated proteins were involved in the biomass biosynthesis pathway. The protein expression profiles suggested that the elongation factor G, cell division protein FtsZ, and proteins associated with the ABC transporters were crucial for R. palustris PSB-S tolerance against pyrazosulfuron-ethyl.

CONCLUSION: Up-regulated proteins, including elongation factor G, cell division FtsZ, ATP synthase, and superoxide dismutase, and down-regulated proteins, including ALS III and ABC transporters, as well as some unknown proteins might play roles in R. palustris PSB-S adaptation to pyrazosulfuron-ethyl induced stresses. Functional validations of these candidate proteins should help to develope transgenic crops resistant to pyrazosulfuron-ethyl.}, } @article {pmid30526496, year = {2018}, author = {Qiu, L and Tao, S and He, H and Ding, W and Li, Y}, title = {Transcriptomics reveal the molecular underpinnings of chemosensory proteins in Chlorops oryzae.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {890}, pmid = {30526496}, issn = {1471-2164}, support = {2018NK2094//Hunan Provincial Science and Technology Department (CN)/ ; }, abstract = {BACKGROUND: Chemosensory proteins are a family of insect-specific chemical sensors that sense specific chemical cues and regulate insect behavior. Chemosensory proteins have been identified and analyzed in many insect species, such as Drosophila melanogaster, Bactrocera dorsalis and Calliphora stygia. This research has revealed that these proteins play a crucial role in insect orientation, predation and oviposition. However, little is known about the chemosensory proteins of Chlorops oryzae, a major pest of rice crops throughout Asia.

RESULTS: Comparative transcription analysis of the genes of Chlorops oryzae larvae, pupae and adults identified a total of 104 chemosensory genes, including 25 odorant receptors (ORs), 26 odorant-binding proteins (OBPs), 19 ionotropic receptors (IRs), 23 gustatory receptors (GRs) and 11 sensory neuron membrane proteins (SNMPs). The sequences of these candidate chemosensory genes were confirmed and used to construct phylogenetic trees. Quantitative real-time PCR (qRT-PCR) confirmed that the expression of candidate OR genes in different developmental stages was consistent with the fragments per kilobase per million fragments (FPKM) values of differentially expressed genes (DEGs).

CONCLUSIONS: The identification of chemosensory genes in C. oryzae provides a foundation for the investigation of the function of chemosensory proteins in this species, which, in turn, could allow the development of new, improved methods of controlling this pest.}, } @article {pmid30526495, year = {2018}, author = {Genova, F and Longeri, M and Lyons, LA and Bagnato, A and , and Strillacci, MG}, title = {First genome-wide CNV mapping in FELIS CATUS using next generation sequencing data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {895}, pmid = {30526495}, issn = {1471-2164}, support = {R01 AR067925/AR/NIAMS NIH HHS/United States ; MT-13-010//Winn Feline Foundation and the George Sydney and Phyllis Redman Miller Trust/ ; MT-13-010//National Geographic Society Education Foundation/ ; Internal funds//Università degli Studi di Milano/ ; }, abstract = {BACKGROUND: Copy Number Variations (CNVs) have becoming very significant variants, representing a major source of genomic variation. CNVs involvement in phenotypic expression and different diseases has been widely demonstrated in humans as well as in many domestic animals. However, genome wide investigation on these structural variations is still missing in Felis catus. The present work is the first CNV mapping from a large data set of Next Generation Sequencing (NGS) data in the domestic cat, performed within the 99 Lives Consortium.

RESULTS: Reads have been mapped on the reference assembly_6.2 by Maverix Biomics. CNV detection with cn.MOPS and CNVnator detected 592 CNVs. These CNVs were used to obtain 154 CNV Regions (CNVRs) with BedTools, including 62 singletons. CNVRs covered 0.26% of the total cat genome with 129 losses, 19 gains and 6 complexes. Cluster Analysis and Principal Component Analysis of the detected CNVRs showed that breeds tend to cluster together as well as cats sharing the same geographical origins. The 46 genes identified within the CNVRs were annotated.

CONCLUSION: This study has improved the genomic characterization of 14 cat breeds and has provided CNVs information that can be used for studies of traits in cats. It can be considered a sound starting point for genomic CNVs identification in this species.}, } @article {pmid30526493, year = {2018}, author = {Chen, Y and Shenkar, N and Ni, P and Lin, Y and Li, S and Zhan, A}, title = {Rapid microevolution during recent range expansion to harsh environments.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {187}, pmid = {30526493}, issn = {1471-2148}, mesh = {Adaptation, Physiological/genetics ; Animals ; Bayes Theorem ; *Biological Evolution ; Ciona intestinalis/*genetics/physiology ; *Ecosystem ; Gene Frequency/genetics ; Gene Ontology ; Genetic Loci ; Genetic Variation ; Genetics, Population ; Genome ; Microsatellite Repeats/genetics ; Molecular Sequence Annotation ; Selection, Genetic ; }, abstract = {BACKGROUND: Adaptive evolution is one of the crucial mechanisms for organisms to survive and thrive in new environments. Recent studies suggest that adaptive evolution could rapidly occur in species to respond to novel environments or environmental challenges during range expansion. However, for environmental adaptation, many studies successfully detected phenotypic features associated with local environments, but did not provide ample genetic evidence on microevolutionary dynamics. It is therefore crucial to thoroughly investigate the genetic basis of rapid microevolution in response to environmental changes, in particular on what genes and associated variation are responsible for environmental challenges. Here, we genotyped genome-wide gene-associated microsatellites to detect genetic signatures of rapid microevolution of a marine tunicate invader, Ciona robusta, during recent range expansion to the harsh environment in the Red Sea.

RESULTS: The Red Sea population was significantly differentiated from the other global populations. The genome-wide scan, as well as multiple analytical methods, successfully identified a set of adaptive genes. Interestingly, the allele frequency largely varied at several adaptive loci in the Red Sea population, and we found significant correlations between allele frequency and local environmental factors at these adaptive loci. Furthermore, a set of genes were annotated to get involved in local temperature and salinity adaptation, and the identified adaptive genes may largely contribute to the invasion success to harsh environments.

CONCLUSIONS: All the evidence obtained in this study clearly showed that environment-driven selection had left detectable signatures in the genome of Ciona robusta within a few generations. Such a rapid microevolutionary process is largely responsible for the harsh environmental adaptation and therefore contributes to invasion success in different aquatic ecosystems with largely varied environmental factors.}, } @article {pmid30526492, year = {2018}, author = {Soe, S and Park, Y and Chae, H}, title = {BiSpark: a Spark-based highly scalable aligner for bisulfite sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {472}, pmid = {30526492}, issn = {1471-2105}, support = {2017R1C1B5018165//Ministry of Science ICT and Future Planning/ ; NRF-2016R1D1A1A02937186//National Research Foundation of Korea/ ; 1-1703-2032//Sookmyung Women's University/ ; HI15C3224//Korea Health Industry Development Institute/Republic of Korea ; }, mesh = {Algorithms ; DNA Methylation/genetics ; Humans ; *Sequence Alignment ; Sequence Analysis, DNA/*methods ; *Software ; Sulfites/*chemistry ; }, abstract = {BACKGROUND: Bisulfite sequencing is one of the major high-resolution DNA methylation measurement method. Due to the selective nucleotide conversion on unmethylated cytosines after treatment with sodium bisulfite, processing bisulfite-treated sequencing reads requires additional steps which need high computational demands. However, a dearth of efficient aligner that is designed for bisulfite-treated sequencing becomes a bottleneck of large-scale DNA methylome analyses.

RESULTS: In this study, we present a highly scalable, efficient, and load-balanced bisulfite aligner, BiSpark, which is designed for processing large volumes of bisulfite sequencing data. We implemented the BiSpark algorithm over the Apache Spark, a memory optimized distributed data processing framework, to achieve the maximum data parallel efficiency. The BiSpark algorithm is designed to support redistribution of imbalanced data to minimize delays on large-scale distributed environment.

CONCLUSIONS: Experimental results on methylome datasets show that BiSpark significantly outperforms other state-of-the-art bisulfite sequencing aligners in terms of alignment speed and scalability with respect to dataset size and a number of computing nodes while providing highly consistent and comparable mapping results.

AVAILABILITY: The implementation of BiSpark software package and source code is available at https://github.com/bhi-kimlab/BiSpark/ .}, } @article {pmid30526490, year = {2018}, author = {Li, X and Ma, Y and Liang, S and Tian, Y and Yin, S and Xie, S and Xie, H}, title = {Comparative genomics of 84 Pectobacterium genomes reveals the variations related to a pathogenic lifestyle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {889}, pmid = {30526490}, issn = {1471-2164}, support = {BAIC07//Earmarked Fund for Beijing Innovation Consortium of Agriculture Research System/ ; }, abstract = {BACKGROUND: Pectobacterium spp. are necrotrophic bacterial plant pathogens of the family Pectobacteriaceae, responsible for a wide spectrum of diseases of important crops and ornamental plants including soft rot, blackleg, and stem wilt. P. carotovorum is a genetically heterogeneous species consisting of three valid subspecies, P. carotovorum subsp. brasiliense (Pcb), P. carotovorum subsp. carotovorum (Pcc), and P. carotovorum subsp. odoriferum (Pco).

RESULTS: Thirty-two P. carotovorum strains had their whole genomes sequenced, including the first complete genome of Pco and another circular genome of Pcb, as well as the high-coverage genome sequences for 30 additional strains covering Pcc, Pcb, and Pco. In combination with 52 other publicly available genome sequences, the comparative genomics study of P. carotovorum and other four closely related species P. polaris, P. parmentieri, P. atrosepticum, and Candidatus P. maceratum was conducted focusing on CRISPR-Cas defense systems and pathogenicity determinants. Our analysis identified two CRISPR-Cas types (I-F and I-E) in Pectobacterium, as well as another I-C type in Dickeya that is not found in Pectobacterium. The core pathogenicity factors (e.g., plant cell wall-degrading enzymes) were highly conserved, whereas some factors (e.g., flagellin, siderophores, polysaccharides, protein secretion systems, and regulatory factors) were varied among these species and/or subspecies. Notably, a novel type of T6SS as well as the sorbitol metabolizing srl operon was identified to be specific to Pco in Pectobacterium.

CONCLUSIONS: This study not only advances the available knowledge about the genetic differentiation of individual subspecies of P. carotovorum, but also delineates the general genetic features of P. carotovorum by comparison with its four closely related species, thereby substantially enriching the extent of information now available for functional genomic investigations about Pectobacterium.}, } @article {pmid30526489, year = {2018}, author = {Pomaznoy, M and Ha, B and Peters, B}, title = {GOnet: a tool for interactive Gene Ontology analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {470}, pmid = {30526489}, issn = {1471-2105}, mesh = {Algorithms ; Animals ; *Gene Ontology ; Humans ; Mice ; *Software ; }, abstract = {BACKGROUND: Biological interpretation of gene/protein lists resulting from -omics experiments can be a complex task. A common approach consists of reviewing Gene Ontology (GO) annotations for entries in such lists and searching for enrichment patterns. Unfortunately, there is a gap between machine-readable output of GO software and its human-interpretable form. This gap can be bridged by allowing users to simultaneously visualize and interact with term-term and gene-term relationships.

RESULTS: We created the open-source GOnet web-application (available at http://tools.dice-database.org/GOnet/), which takes a list of gene or protein entries from human or mouse data and performs GO term annotation analysis (mapping of provided entries to GO subsets) or GO term enrichment analysis (scanning for GO categories overrepresented in the input list). The application is capable of producing parsable data formats and importantly, interactive visualizations of the GO analysis results. The interactive results allow exploration of genes and GO terms as a graph that depicts the natural hierarchy of the terms and retains relationships between terms and genes/proteins. As a result, GOnet provides insight into the functional interconnection of the submitted entries.

CONCLUSIONS: The application can be used for GO analysis of any biological data sources resulting in gene/protein lists. It can be helpful for experimentalists as well as computational biologists working on biological interpretation of -omics data resulting in such lists.}, } @article {pmid30526487, year = {2018}, author = {Liu, J and Li, CQ and Dong, Y and Yang, X and Wang, YZ}, title = {Dosage imbalance of B- and C-class genes causes petaloid-stamen relating to F1 hybrid variation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {341}, pmid = {30526487}, issn = {1471-2229}, support = {nos. 31170198//National Natural Science Foundation of China/ ; nos.31530003//National Natural Science Foundation of China/ ; }, mesh = {Flowers/*genetics/growth & development/ultrastructure ; Gene Dosage/genetics ; Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics/physiology ; Magnoliopsida/genetics/growth & development ; Microscopy, Electron, Scanning ; Phylogeny ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Great advances have been achieved in our understanding of flower development and evolution since the establishment of the ABC model. However, it remains a challenge to define the exact context of organ identity in the component interactions of the ABC model.

RESULTS: Through hybridization, we detected a homeotic mutant in Petrocosmea (Gesneriaceae) uniquely displayed by the 'petaloid-stamen' in the third whorl with petal identity. Comparative Real-time PCR analyses demonstrate that both two B-class genes DEF2 and GLO are excessively expressed while the transcripts of the C-class gene PLE are reduced in the third floral whorl in the mutant compared to that in the wild-type F1 hybrids. Further allele-specific expression (ASE) analyses indicate that an allele-specific change in PgPLE might be responsible for up-regulation of both B-class genes and down-regulation of the C-class gene in the petaloid-stamen mutants.

CONCLUSIONS: Our findings suggest that the petaloid-stamen is consequent upon an evident dosage imbalance between B- and C-class products that is probably triggered by a cis-regulatory change. In addition, the genetic pathway for the floral organ identity might be in parallel with that for the floral symmetry. The extreme variation in hybrids further suggests that interspecific hybridization may represent a major factor for evolutionary innovation and diversification in plants.}, } @article {pmid30526486, year = {2018}, author = {Dey, KK and Xie, D and Stephens, M}, title = {A new sequence logo plot to highlight enrichment and depletion.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {473}, pmid = {30526486}, issn = {1471-2105}, support = {CA198933//National Institutes of Health/ ; }, mesh = {Amino Acid Sequence ; Base Sequence ; Bayes Theorem ; DNA/chemistry ; Humans ; *Sequence Alignment ; Software ; }, abstract = {BACKGROUND: Sequence logo plots have become a standard graphical tool for visualizing sequence motifs in DNA, RNA or protein sequences. However standard logo plots primarily highlight enrichment of symbols, and may fail to highlight interesting depletions. Current alternatives that try to highlight depletion often produce visually cluttered logos.

RESULTS: We introduce a new sequence logo plot, the EDLogo plot, that highlights both enrichment and depletion, while minimizing visual clutter. We provide an easy-to-use and highly customizable R package Logolas to produce a range of logo plots, including EDLogo plots. This software also allows elements in the logo plot to be strings of characters, rather than a single character, extending the range of applications beyond the usual DNA, RNA or protein sequences. And the software includes new Empirical Bayes methods to stabilize estimates of enrichment and depletion, and thus better highlight the most significant patterns in data. We illustrate our methods and software on applications to transcription factor binding site motifs, protein sequence alignments and cancer mutation signature profiles.

CONCLUSIONS: Our new EDLogo plots and flexible software implementation can help data analysts visualize both enrichment and depletion of characters (DNA sequence bases, amino acids, etc.) across a wide range of applications.}, } @article {pmid30526485, year = {2018}, author = {Wu, C and Lan, L and Li, Y and Nie, Z and Zeng, R}, title = {The relationship between latex metabolism gene expression with rubber yield and related traits in Hevea brasiliensis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {897}, pmid = {30526485}, issn = {1471-2164}, support = {ZDKJ2016020//Major Scientific & Technological Projects of Hainan Province/ ; No. CARS-33//China Agriculture Research System/ ; }, abstract = {BACKGROUND: Expression patterns of many laticifer-specific gens are closely correlative with rubber yield of Hevea brasiliensis (para rubber tree). To unveil the mechanisms underlying the rubber yield, transcript levels of nine major latex metabolism-related genes, i.e., HMG-CoA synthase (HMGS), HMG-CoA reductase (HMGR), diphosphomevalonate decarboxylase (PMD), farnesyl diphosphate synthase (FPS), cis-prenyltransferase (CPT), rubber elongation factor (REF), small rubber particle protein (SRPP), dihydroxyacid dehydratase (DHAD) and actin depolymerizing factor (ADF), were dertermined, and the relationship between rubber yield with their expression levels was analysed.

RESULTS: Except HbHMGR1, HbPMD and HbDHAD, most of these genes were predominantly expressed in latex, and bark tapping markedly elevated the transcript abundance of the analyzed genes, with the 7th tapping producing the greatest expression levels. Both ethephon (ETH) and methyl jasmonate (MeJA) stimulation greatly induced the expression levels of the examined genes, at least at one time point, except HbDHAD, which was unresponsive to MeJA. The genes' expression levels, as well as the rubber yields and two yield characteristics differed significantly among the different genotypes examined. Additionally, the latex and dry rubber yields increased gradually but the dry rubber content did not. Rubber yields and/or yield characteristics were significantly positively correlated with HbCPT, HbFPS, HbHMGS, HbHMGR1 and HbDHAD expression levels, negatively correlated with that of HbREF, but not significantly correlated with HbPMD, HbSRPP and HbADF expression levels. In addition, during rubber production, significantly positive correlations existed between the expression level of HbPMD and the levels of HbREF and HbHMGR1, between HbSRPP and the levels of HbHMGS and HbHMGR1, and between HbADF and HbFPS.

CONCLUSIONS: The up-regulation of these genes might be related to the latex production of rubber trees under the stress of bark tapping and latex metabolism. The various correlations among the genes implied that there are differences in their synergic interactions. Thus, these nine genes might be related to rubber yield and yield-related traits in H. brasiliensis, and this work increases our understanding of their complex functions and how they are expressed in both high-and medium-yield rubber tree varieties and low-yield wild rubber tree germplasm.}, } @article {pmid30526484, year = {2018}, author = {Zhou, R and Liu, P and Li, D and Zhang, X and Wei, X}, title = {Photoperiod response-related gene SiCOL1 contributes to flowering in sesame.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {343}, pmid = {30526484}, issn = {1471-2229}, support = {31671282//National Natural Science Foundation of China/ ; }, mesh = {Arabidopsis ; Conserved Sequence/genetics ; Flowers/*growth & development/physiology ; Gene Expression Regulation, Plant ; Genes, Plant/genetics/*physiology ; Haplotypes ; Photoperiod ; Phylogeny ; Plant Proteins/*physiology ; Plants, Genetically Modified ; Real-Time Polymerase Chain Reaction ; Sesamum/genetics/*growth & development/physiology ; Transcription Factors/genetics/*physiology ; }, abstract = {BACKGROUND: Sesame is a major oilseed crop which is widely cultivated all around the world. Flowering, the timing of transition from vegetative to reproductive growth, is one of the most important events in the life cycle of sesame. Sesame is a typical short-day (SD) plant and its flowering is largely affected by photoperiod. However, the flowering mechanism in sesame at the molecular level is still not very clear. Previous studies showed that the CONSTANS (CO) gene is the crucial photoperiod response gene which plays a center role in duration of the plant vegetative growth.

RESULTS: In this study, the CO-like (COL) genes were identified and characterized in the sesame genome. Two homologs of the CO gene in the SiCOLs, SiCOL1 and SiCOL2, were recognized and comprehensively analyzed. However, sequence analysis showed that SiCOL2 lacked one of the B-box motifs. In addition, the flowering time of the transgenic Arabidopsis lines with overexpressed SiCOL2 were longer than that of SiCOL1, indicating that SiCOL1 was more likely to be the potential functional homologue of CO in sesame. Expression analysis revealed that SiCOL1 had high expressed levels before flowering in leaves and exhibited diurnal rhythmic expression in both SD and long-day (LD) conditions. In total, 16 haplotypes of SiCOL1 were discovered in the sesame collections from Asia. However, the mutated haplotypes did not express under both SD and LD conditions and was regarded as a nonfunctional allele. Notably, the sesame landraces from high-latitude regions harboring nonfunctional alleles of SiCOL1 flowered much earlier than landraces from low-latitude regions under LD condition, and adapted to the northernmost regions of sesame cultivation. The result indicated that sesame landraces from high-latitude regions might have undergone artificial selection to adapt to the LD environment.

CONCLUSIONS: Our results suggested that SiCOL1 might contribute to regulation of flowering in sesame and natural variations in SiCOL1 were probably related to the expansion of sesame cultivation to high-latitude regions. The results could be used in sesame breeding and in broadening adaptation of sesame varieties to new regions.}, } @article {pmid30526483, year = {2018}, author = {Singh, A and Massicotte, MA and Garand, A and Tousignant, L and Ouellette, V and Bérubé, G and Desgagné-Penix, I}, title = {Cloning and characterization of norbelladine synthase catalyzing the first committed reaction in Amaryllidaceae alkaloid biosynthesis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {338}, pmid = {30526483}, issn = {1471-2229}, support = {RGPIN 05294-2014//Natural Sciences and Engineering Research Council of Canada/ ; EQPEQ 472990-2015//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Amaryllidaceae/*enzymology/genetics/metabolism ; Amaryllidaceae Alkaloids/*metabolism ; Amino Acid Sequence ; Benzaldehydes/metabolism ; Carbon-Nitrogen Ligases/genetics/metabolism ; Catechols/metabolism ; Cloning, Molecular ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Alignment ; Tyramine/metabolism ; }, abstract = {BACKGROUND: Amaryllidaceae alkaloids (AAs) are a large group of plant-specialized metabolites displaying an array of biological and pharmacological properties. Previous investigations on AA biosynthesis have revealed that all AAs share a common precursor, norbelladine, presumably synthesized by an enzyme catalyzing a Mannich reaction involving the condensation of tyramine and 3,4-dihydroxybenzaldehyde. Similar reactions have been reported. Specifically, norcoclaurine synthase (NCS) which catalyzes the condensation of dopamine and 4-hydroxyphenylacetaldehyde as the first step in benzylisoquinoline alkaloid biosynthesis.

RESULTS: With the availability of wild daffodil (Narcissus pseudonarcissus) database, a transcriptome-mining search was performed for NCS orthologs. A candidate gene sequence was identified and named norbelladine synthase (NBS). NpNBS encodes for a small protein of 19 kDa with an anticipated pI of 5.5. Phylogenetic analysis showed that NpNBS belongs to a unique clade of PR10/Bet v1 proteins and shared 41% amino acid identity to opium poppy NCS1. Expression of NpNBS cDNA in Escherichia coli produced a recombinant enzyme able to condense tyramine and 3,4-DHBA into norbelladine as determined by high-resolution tandem mass spectrometry.

CONCLUSIONS: Here, we describe a novel enzyme catalyzing the first committed step of AA biosynthesis, which will facilitate the establishment of metabolic engineering and synthetic biology platforms for the production of AAs.}, } @article {pmid30526482, year = {2018}, author = {Tang, K and Ren, J and Cronn, R and Erickson, DL and Milligan, BG and Parker-Forney, M and Spouge, JL and Sun, F}, title = {Alignment-free genome comparison enables accurate geographic sourcing of white oak DNA.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {896}, pmid = {30526482}, issn = {1471-2164}, support = {DMS-1518001//National Science Foundation/ ; }, abstract = {BACKGROUND: The application of genomic data and bioinformatics for the identification of restricted or illegally-sourced natural products is urgently needed. The taxonomic identity and geographic provenance of raw and processed materials have implications in sustainable-use commercial practices, and relevance to the enforcement of laws that regulate or restrict illegally harvested materials, such as timber. Improvements in genomics make it possible to capture and sequence partial-to-complete genomes from challenging tissues, such as wood and wood products.

RESULTS: In this paper, we report the success of an alignment-free genome comparison method, [Formula: see text] that differentiates different geographic sources of white oak (Quercus) species with a high level of accuracy with very small amount of genomic data. The method is robust to sequencing errors, different sequencing laboratories and sequencing platforms.

CONCLUSIONS: This method offers an approach based on genome-scale data, rather than panels of pre-selected markers for specific taxa. The method provides a generalizable platform for the identification and sourcing of materials using a unified next generation sequencing and analysis framework.}, } @article {pmid30526481, year = {2018}, author = {Fay, JV and Watkins, CJ and Shrestha, RK and Litwiñiuk, SL and Talavera Stefani, LN and Rojas, CA and Argüelles, CF and Ferreras, JA and Caccamo, M and Miretti, MM}, title = {Yerba mate (Ilex paraguariensis, A. St.-Hil.) de novo transcriptome assembly based on tissue specific genomic expression profiles.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {891}, pmid = {30526481}, issn = {1471-2164}, support = {PIO - CONICET//Consejo Nacional de Investigaciones Científicas y Técnicas (AR)/ ; }, abstract = {BACKGROUND: The most common infusion in southern Latin-American countries is prepared with dried leaves of Ilex paraguariensis A. St.-Hil., an aboriginal ancestral beverage known for its high polyphenols concentration currently consumed in > 90% of homes in Argentina, in Paraguay and Uruguay. The economy of entire provinces heavily relies on the production, collection and manufacture of Ilex paraguariensis, the fifth plant species with highest antioxidant activity. Polyphenols are associated to relevant health benefits including strong antioxidant properties. Despite its regional relevance and potential biotechnological applications, little is known about functional genomics and genetics underlying phenotypic variation of relevant traits. By generating tissue specific transcriptomic profiles, we aimed to comprehensively annotate genes in the Ilex paraguariensis phenylpropanoid pathway and to evaluate differential expression profiles.

RESULTS: In this study we generated a reliable transcriptome assembly based on a collection of 15 RNA-Seq libraries from different tissues of Ilex paraguariensis. A total of 554 million RNA-Seq reads were assembled into 193,897 transcripts, where 24,612 annotated full-length transcripts had complete ORF. We assessed the transcriptome assembly quality, completeness and accuracy using BUSCO and TransRate; consistency was also evaluated by experimentally validating 11 predicted genes by PCR and sequencing. Functional annotation against KEGG Pathway database identified 1395 unigenes involved in biosynthesis of secondary metabolites, 531 annotated transcripts corresponded to the phenylpropanoid pathway. The top 30 differentially expressed genes among tissue revealed genes involved in photosynthesis and stress response. These significant differences were then validated by qRT-PCR.

CONCLUSIONS: Our study is the first to provide data from whole genome gene expression profiles in different Ilex paraguariensis tissues, experimentally validating in-silico predicted genes key to the phenylpropanoid (antioxidant) pathway. Our results provide essential genomic data of potential use in breeding programs for polyphenol content. Further studies are necessary to assess if the observed expression variation in the phenylpropanoid pathway annotated genes is related to variations in leaves' polyphenol content at the population scale. These results set the current reference for Ilex paraguariensis genomic studies and provide a substantial contribution to research and biotechnological applications of phenylpropanoid secondary metabolites.}, } @article {pmid30526480, year = {2018}, author = {Xia, Y and Luo, W and Yuan, S and Zheng, Y and Zeng, X}, title = {Microsatellite development from genome skimming and transcriptome sequencing: comparison of strategies and lessons from frog species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {886}, pmid = {30526480}, issn = {1471-2164}, support = {NSFC-31401960//National Natural Science Foundation of China/ ; NSFC-31572241//National Natural Science Foundation of China/ ; NSFC-31572243//National Natural Science Foundation of China/ ; 2014 M552386//China Postdoctoral Science Foundation/ ; 2017YFC0505202//National Key Programme of Research and Development, Ministry of Science and Technology/ ; }, abstract = {BACKGROUND: Even though microsatellite loci frequently have been isolated using recently developed next-generation sequencing (NGS) techniques, this task is still difficult because of the subsequent polymorphism screening requires a substantial amount of time. Selecting appropriate polymorphic microsatellites is a critical issue for ecological and evolutionary studies. However, the extent to which assembly strategy, read length, sequencing depth, and library layout produce a measurable effect on microsatellite marker development remains unclear. Here, we use six frog species for genome skimming and two frog species for transcriptome sequencing to develop microsatellite markers, and investigate the effect of different isolation strategies on the yield of microsatellites.

RESULTS: The results revealed that the number of isolated microsatellites increases with increased data quantity and read length. Assembly strategy could influence the yield and the polymorphism of microsatellite development. Larger k-mer sizes produced fewer total number of microsatellite loci, but these loci had a longer repeat length, suggesting greater polymorphism. However, the proportion of each type of nucleotide repeats was not affected; dinucleotide repeats were always the dominant type. Finally, the transcriptomic microsatellites displayed lower levels of polymorphisms and were less abundant than genomic microsatellites, but more likely to be functionally linked loci.

CONCLUSIONS: These observations provide deep insight into the evolution and distribution of microsatellites and how different isolation strategies affect microsatellite development using NGS.}, } @article {pmid30526479, year = {2018}, author = {Tarr, SJ and Díaz-Ingelmo, O and Stewart, LB and Hocking, SE and Murray, L and Duffy, CW and Otto, TD and Chappell, L and Rayner, JC and Awandare, GA and Conway, DJ}, title = {Schizont transcriptome variation among clinical isolates and laboratory-adapted clones of the malaria parasite Plasmodium falciparum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {894}, pmid = {30526479}, issn = {1471-2164}, support = {AdG-2011- 294428//FP7 Ideas: European Research Council/ ; AA110050//Royal Society/ ; 294428//European Research Council/International ; LIDO Doctoral Training Programme Studentship//Biotechnology and Biological Sciences Research Council/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Malaria parasites are genetically polymorphic and phenotypically plastic. In studying transcriptome variation among parasites from different infections, it is challenging to overcome potentially confounding technical and biological variation between samples. We investigate variation in the major human parasite Plasmodium falciparum, generating RNA-seq data on multiple independent replicate sample preparations of merozoite-containing intra-erythrocytic schizonts from a panel of clinical isolates and from long-term laboratory-adapted clones, with a goal of robustly identifying differentially expressed genes.

RESULTS: Analysis of biological sample replicates shows that increased numbers improve the true discovery rate of differentially expressed genes, and that six independent replicates of each parasite line allowed identification of most differences that could be detected with larger numbers. For highly expressed genes, focusing on the top quartile at schizont stages, there was more power to detect differences. Comparing cultured clinical isolates and laboratory-adapted clones, genes more highly expressed in the laboratory-adapted clones include those encoding an AP2 transcription factor (PF3D7_0420300), a ubiquitin-binding protein and two putative methyl transferases. In contrast, higher expression in clinical isolates was seen for the merozoite surface protein gene dblmsp2, proposed to be a marker of schizonts forming merozoites committed to sexual differentiation. Variable expression was extremely strongly, but not exclusively, associated with genes known to be targeted by Heterochromatin Protein 1. Clinical isolates show variable expression of several known merozoite invasion ligands, as well as other genes for which new RT-qPCR assays validate the quantitation and allow characterisation in samples with more limited material. Expression levels of these genes vary among schizont preparations of different clinical isolates in the first ex vivo cycle in patient erythrocytes, but mean levels are similar to those in continuously cultured clinical isolates.

CONCLUSIONS: Analysis of multiple biological sample replicates greatly improves identification of genes variably expressed between different cultured parasite lines. Clinical isolates recently established in culture show differences from long-term adapted clones in transcript levels of particular genes, and are suitable for analyses requiring biological replicates to understand parasite phenotypes and variable expression likely to be relevant in nature.}, } @article {pmid30526478, year = {2018}, author = {Xu, S and Hao, X and Zhang, M and Wang, K and Li, S and Chen, X and Yang, L and Hu, L and Zhang, S}, title = {Polymorphisms of HOMER1 gene are associated with piglet splay leg syndrome and one significant SNP can affect its intronic promoter activity in vitro.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {110}, pmid = {30526478}, issn = {1471-2156}, support = {52902-0650104//Promote the scientific research cooperation with America-Pacificregionand and high-level training project/ ; YSF2015000414//Wuhan yellow crane plan/ ; }, abstract = {BACKGROUND: In our previous genome-wide association study (GWAS) on the piglet splay leg (PSL) syndrome, the homer scaffolding protein 1 (HOMER1) was detected as a candidate gene. The aim of this work was to further verify the candidate gene by sequencing the gene and find the significantly associated mutation. Then we preliminarily analyzed the effect of the significant SNP on intronic promoter activity. This research provided a reference for further investigation of the pathogenesis of PSL.

RESULT: We investigated the 19 SNPs on HOMER1 and found 12 SNPs significant associated with PSL, including 8 SNPs resided in the potential intronic promoter region in intron 4. The - 663~ - 276 bp upstream the exon 5 had promoter activity and it could be an intronic promoter that regulated the transcription of HOMER1-205 transcript. The promoter activity of the - 663~ - 276 bp containing the rs339135425 and rs325197091 mutant alleles was significantly higher than of the wild type (P < 0.05). The G allele of rs325197091 (A > G) may create a new binding site of transcription factor aryl hydrocarbon receptor nuclear translocator (ARNT) and could enhance HOMER1 intronic promoter activity.

CONCLUSIONS: HOMER1 gene was associated with the PSL, and the rs325197091 could influence HOMER1 intronic promoter activity in vitro.}, } @article {pmid30526477, year = {2018}, author = {Graze, RM and Tzeng, RY and Howard, TS and Arbeitman, MN}, title = {Perturbation of IIS/TOR signaling alters the landscape of sex-differential gene expression in Drosophila.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {893}, pmid = {30526477}, issn = {1471-2164}, support = {R01GM073039//National Institutes of Health/ ; 1751296//Division of Environmental Biology/ ; }, abstract = {BACKGROUND: The core functions of the insulin/insulin-like signaling and target of rapamycin (IIS/TOR) pathway are nutrient sensing, energy homeostasis, growth, and regulation of stress responses. This pathway is also known to interact directly and indirectly with the sex determination regulatory hierarchy. The IIS/TOR pathway plays a role in directing sexually dimorphic traits, including dimorphism of growth, metabolism, stress and behavior. Previous studies of sexually dimorphic gene expression in the adult head, which includes both nervous system and endocrine tissues, have revealed variation in sex-differential expression, depending in part on genotype and environment. To understand the degree to which the environmentally responsive insulin signaling pathway contributes to sexual dimorphism of gene expression, we examined the effect of perturbation of the pathway on gene expression in male and female Drosophila heads.

RESULTS: Our data reveal a large effect of insulin signaling on gene expression, with greater than 50% of genes examined changing expression. Males and females have a shared gene expression response to knock-down of InR function, with significant enrichment for pathways involved in metabolism. Perturbation of insulin signaling has a greater impact on gene expression in males, with more genes changing expression and with gene expression differences of larger magnitude. Primarily as a consequence of the response in males, we find that reduced insulin signaling results in a striking increase in sex-differential expression. This includes sex-differences in expression of immune, defense and stress response genes, genes involved in modulating reproductive behavior, genes linking insulin signaling and ageing, and in the insulin signaling pathway itself.

CONCLUSIONS: Our results demonstrate that perturbation of insulin signaling results in thousands of genes displaying sex differences in expression that are not differentially expressed in control conditions. Thus, insulin signaling may play a role in variability of somatic, sex-differential expression. The finding that perturbation of the IIS/TOR pathway results in an altered landscape of sex-differential expression suggests a role of insulin signaling in the physiological underpinnings of trade-offs, sexual conflict and sex differences in expression variability.}, } @article {pmid30526476, year = {2018}, author = {Lu, Q and Liu, H and Hong, Y and Li, H and Liu, H and Li, X and Wen, S and Zhou, G and Li, S and Chen, X and Liang, X}, title = {Consensus map integration and QTL meta-analysis narrowed a locus for yield traits to 0.7 cM and refined a region for late leaf spot resistance traits to 0.38 cM on linkage group A05 in peanut (Arachis hypogaea L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {887}, pmid = {30526476}, issn = {1471-2164}, support = {31771841//the National Natural Science Foundation of China/ ; 31501246//the National Natural Science Foundation of China/ ; 2013B020301014, 2013B050800021, 2015A030313565, 2015B020231006, 2016B020201003, 2017A030311007//the Science and Technology Planning Project of Guangdong Province/ ; CARS-13//the Modern Agro-industry Technology Research System/ ; 2016LM3161, 2016LM3164//the Research and Demonstration of Agricultural Technology Demand in Guangdong/ ; 201609//the Key Discipline Construction of the Guangdong Academy of Agricultural Sciences/ ; 201831//the Special Foundation of President of the Guangdong Academy of Agricultural Sciences/ ; }, abstract = {BACKGROUND: Many large-effect quantitative trait loci (QTLs) for yield and disease resistance related traits have been identified in different mapping populations of peanut (Arachis hypogaea L.) under multiple environments. However, only a limited number of QTLs have been used in marker-assisted selection (MAS) because of unfavorable epistatic interactions between QTLs in different genetic backgrounds. Thus, it is essential to identify consensus QTLs across different environments and genetic backgrounds for use in MAS. Here, we used QTL meta-analysis to identify a set of consensus QTLs for yield and disease resistance related traits in peanut.

RESULTS: A new integrated consensus genetic map with 5874 loci was constructed. The map comprised 20 linkage groups (LGs) and was up to a total length of 2918.62 cM with average marker density of 2.01 loci per centimorgan (cM). A total of 292 initial QTLs were projected on the new consensus map, and 40 meta-QTLs (MQTLs) for yield and disease resistance related traits were detected on four LGs. The genetic intervals of these consensus MQTLs varied from 0.20 cM to 7.4 cM, which is narrower than the genetic intervals of the initial QTLs, meaning they may be suitable for use in MAS. Importantly, a region of the map that previously co-localized multiple major QTLs for pod traits was narrowed from 3.7 cM to 0.7 cM using an overlap region of four MQTLs for yield related traits on LG A05, which corresponds to a physical region of about 630.3 kb on the A05 pseudomolecule of peanut, including 38 annotated candidate genes (54 transcripts) related to catalytic activity and metabolic process. Additionally, one major MQTL for late leaf spot (LLS) was identified in a region of about 0.38 cM. BLAST searches identified 26 candidate genes (30 different transcripts) in this region, some of which were annotated as related to regulation of disease resistance in different plant species.

CONCLUSIONS: Combined with the high-density marker consensus map, all the detected MQTLs could be useful in MAS. The biological functions of the 64 candidate genes should be validated to unravel the molecular mechanisms of yield and disease resistance in peanut.}, } @article {pmid30526475, year = {2018}, author = {Papaianni, M and Contaldi, F and Fulgione, A and Woo, SL and Casillo, A and Corsaro, MM and Parrilli, E and Marcolungo, L and Rossato, M and Delledonne, M and Garonzi, M and Iannelli, D and Capparelli, R}, title = {Role of phage ϕ1 in two strains of Salmonella Rissen, sensitive and resistant to phage ϕ1.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {208}, pmid = {30526475}, issn = {1471-2180}, abstract = {BACKGROUND: The study describes the Salmonella Rissen phage ϕ1 isolated from the ϕ1-sensitive Salmonella Rissen strain RW. The same phage was then used to select the resistant strain RRϕ1+, which can harbour or not ϕ1.

RESULTS: Following this approach, we found that ϕ1, upon excision from RW cells with mitomycin, behaves as a temperate phage: lyses host cells and generates phage particles; instead, upon spontaneous excision from RRϕ1+ cells, it does not generate phage particles; causes loss of phage resistance; switches the O-antigen from the smooth to the rough phenotype, and favors the transition of Salmonella Rissen from the planktonic to the biofilm growth. The RW and RRϕ1+ strains differ by 10 genes; of these, only two (phosphomannomutase_1 and phosphomannomutase_2; both involved in the mannose synthesis pathway) display significant differences at the expression levels. This result suggests that phage resistance is associated with these two genes.

CONCLUSIONS: Phage ϕ1 displays the unusual property of behaving as template as well as lytic phage. This feature was used by the phage to modulate several phases of Salmonella Rissen lifestyle.}, } @article {pmid30526474, year = {2018}, author = {López Juri, G and Chiaraviglio, M and Cardozo, G}, title = {Macroevolution of sexual size dimorphism and reproduction-related phenotypic traits in lizards of the Chaco Domain.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {186}, pmid = {30526474}, issn = {1471-2148}, mesh = {Animals ; *Biological Evolution ; *Body Size ; Brazil ; Clutch Size ; Female ; Fertility ; Lizards/*anatomy & histology ; Male ; Phenotype ; Phylogeny ; Reproduction ; *Sex Characteristics ; }, abstract = {BACKGROUND: Comparing sexual size dimorphism (SSD) in the light of the phylogenetic hypothesis may help to understand the phenotypic evolution associated with sexual selection (size of whole body and of reproduction-related body parts). Within a macroevolutionary framework, we evaluated the association between the evolution of SSD and the evolution of reproduction-related phenotypic traits, and whether this association has favored female fecundity, considering also variations according to reproductive modes. We focused on the lizard species that inhabit the Chaco Domain since this is a natural unit with a high diversity of species.

RESULTS: The residual SSD was related positively with the residuals of the reproduction-related phenotypic traits that estimate intrasexual selection and with the residuals of inter-limb length and, according to fecundity selection, those residuals were related positively with the residuals of clutch size in oviparous species. Lizards of the Chaco Domain present a high diversity of SSD patterns, probably related to the evolution of reproductive strategies.

CONCLUSIONS: Our findings highlight that the sexual selection may have acted on the whole-body size as well as on the size of body parts related to reproduction. Male and female phenotypes evolutionarily respond to variations in SSD, and an understanding of these patterns is essential for elucidating the processes shaping sexual phenotype diversity from a macroevolutionary perspective.}, } @article {pmid30526473, year = {2018}, author = {Dranca, L and de Abetxuko Ruiz de Mendarozketa, L and Goñi, A and Illarramendi, A and Navalpotro Gomez, I and Delgado Alvarado, M and Cruz Rodríguez-Oroz, M}, title = {Using Kinect to classify Parkinson's disease stages related to severity of gait impairment.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {471}, pmid = {30526473}, issn = {1471-2105}, support = {grant FEDER/TIN2016-78011-C4-2-R//Spanish Ministry of Economy and Competitiveness/ ; }, mesh = {Aged ; Algorithms ; Bayes Theorem ; Female ; Gait/*physiology ; Humans ; Male ; Parkinson Disease/*diagnosis/*physiopathology ; Probability ; *Software ; }, abstract = {BACKGROUND: Parkinson's Disease (PD) is a chronic neurodegenerative disease associated with motor problems such as gait impairment. Different systems based on 3D cameras, accelerometers or gyroscopes have been used in related works in order to study gait disturbances in PD. Kinect Ⓡ has also been used to build these kinds of systems, but contradictory results have been reported: some works conclude that Kinect does not provide an accurate method of measuring gait kinematics variables, but others, on the contrary, report good accuracy results.

METHODS: In this work, we have built a Kinect-based system that can distinguish between different PD stages, and have performed a clinical study with 30 patients suffering from PD belonging to three groups: early PD patients without axial impairment, more evolved PD patients with higher gait impairment but without Freezing of Gait (FoG), and patients with advanced PD and FoG. Those patients were recorded by two Kinect devices when they were walking in a hospital corridor. The datasets obtained from the Kinect were preprocessed, 115 features identified, some methods were applied to select the relevant features (correlation based feature selection, information gain, and consistency subset evaluation), and different classification methods (decision trees, Bayesian networks, neural networks and K-nearest neighbours classifiers) were evaluated with the goal of finding the most accurate method for PD stage classification.

RESULTS: The classifier that provided the best results is a particular case of a Bayesian Network classifier (similar to a Naïve Bayesian classifier) built from a set of 7 relevant features selected by the correlation-based on feature selection method. The accuracy obtained for that classifier using 10-fold cross validation is 93.40%. The relevant features are related to left shin angles, left humerus angles, frontal and lateral bents, left forearm angles and the number of steps during spin.

CONCLUSIONS: In this paper, it is shown that using Kinect is adequate to build a inexpensive and comfortable system that classifies PD into three different stages related to FoG. Compared to the results of previous works, the obtained accuracy (93.40%) can be considered high. The relevant features for the classifier are: a) movement and position of the left arm, b) trunk position for slightly displaced walking sequences, and c) left shin angle, for straight walking sequences. However, we have obtained a better accuracy (96.23%) for a classifier that only uses features extracted from slightly displaced walking steps and spin walking steps. Finally, the obtained set of relevant features may lead to new rehabilitation therapies for PD patients with gait problems.}, } @article {pmid30525926, year = {2018}, author = {Olsson, V and Joos, L and Zhu, S and Gevaert, K and Butenko, MA and De Smet, I}, title = {Look Closely, the Beautiful May Be Small: Precursor-Derived Peptides in Plants.}, journal = {Annual review of plant biology}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-arplant-042817-040413}, pmid = {30525926}, issn = {1545-2123}, abstract = {During the past decade, a flurry of research focusing on the role of peptides as short- and long-distance signaling molecules in plant cell communication has been undertaken. Here,we focus on peptides derived from nonfunctional precursors, and we address several key questions regarding peptide signaling. We provide an overview of the regulatory steps involved in producing a biologically active peptide ligand that can bind its corresponding receptor(s) and discuss how this binding and subsequent activation lead to specific cellular outputs. We discuss different experimental approaches that can be used to match peptide ligands with their receptors. Lastly, we explore how peptides evolved from basic signaling units regulating essential processes in plants to more complex signaling systems as new adaptive traits developed and how nonplant organisms exploit this signaling machinery by producing peptide mimics. Expected final online publication date for the Annual Review of Plant Biology Volume 70 is April 29, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30521846, year = {2018}, author = {Torzewska, A and Bednarska, K and Różalski, A}, title = {Influence of various uropathogens on crystallization of urine mineral components caused by Proteus mirabilis.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.11.005}, pmid = {30521846}, issn = {1769-7123}, abstract = {Infectious urolithiasis is a consequence of long-standing urinary tract infections with urease-positive bacteria, especially Proteus spp. However, because of the often mixed nature of urinary tract infections, in the case of urinary stones formation, several species of bacteria may be involved in the process. The purpose of the study was to determine the impact of the bacterial species: Escherichia coli, Klebsiella pneumoniae, Providencia stuartii, Pseudomonas aeruginosa and Staphylococcus aureus on the crystallization caused by Proteus mirabilis. The studies were conducted in synthetic urine with the addition of P. mirabilis and a representative of another species. During the experiments the viability of bacteria, pH, presence and morphology of crystals, and the intensity of crystallization were assessed. Crystallization of calcium and magnesium phosphates occurred in all investigated configurations. However, there were differences observed in the course and intensity of crystallization between the mixed culture and the P. mirabilis culture. Although most intense crystallization took place in the pure culture of P. mirabilis it was also demonstrated that the presence of other uropathogens increased the survival of P. mirabilis. This synergistic effect could be responsible for the persistence and recurrence of urolithiasis in the urinary tract.}, } @article {pmid30521811, year = {2018}, author = {Kassmer, SH and Nourizadeh, S and De Tomaso, AW}, title = {Cellular and molecular mechanisms of regeneration in colonial and solitary Ascidians.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.11.021}, pmid = {30521811}, issn = {1095-564X}, abstract = {Regenerative ability is highly variable among the metazoans. While many invertebrate organisms are capable of complete regeneration of entire bodies and organs, whole-organ regeneration is limited to very few species in the vertebrate lineages. Tunicates, which are invertebrate chordates and the closest extant relatives of the vertebrates, show robust regenerative ability. Colonial ascidians of the family of the Styelidae, such as several species of Botrylloides, are able to regenerate entire new bodies from nothing but fragments of vasculature, and they are the only chordates that are capable of whole body regeneration. The cell types and signaling pathways involved in whole body regeneration are not well understood, but some evidence suggests that blood borne cells may play a role. Solitary ascidians such as Ciona can regenerate the oral siphon and their central nervous system, and stem cells located in the branchial sac are required for this regeneration. Here, we summarize the cellular and molecular mechanisms of tunicate regeneration that have been identified so far and discuss differences and similarities between these mechanisms in regenerating tunicate species.}, } @article {pmid30521810, year = {2018}, author = {Nishikata, T and Goto, T and Yagi, H and Ishii, H}, title = {Massive cytoplasmic transport and microtubule organization in fertilized chordate eggs.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.11.019}, pmid = {30521810}, issn = {1095-564X}, abstract = {Eggs have developed their own strategies for early development. Amphibian, teleost fish, and ascidian eggs show cortical rotation and an accompanying structure, a cortical parallel microtubule (MT) array, during the one-cell embryonic stage. Cortical rotation is thought to relocate maternal deposits to a certain compartment of the egg and to polarize the embryo. The common features and differences among chordate eggs as well as localized maternal proteins and mRNAs that are related to the organization of MT structures are described in this review. Furthermore, recent studies report progress in elucidating the molecular nature and functions of the noncentrosomal MT organizing center (ncMTOC). The parallel array of MT bundles is presumably organized by ncMTOCs; therefore, the mechanism of ncMTOC control is likely inevitable for these species. Thus, the molecules related to the ncMTOC provide clues for understanding the mechanisms of early developmental systems, which ultimately determine the embryonic axis.}, } @article {pmid30521809, year = {2019}, author = {Attenborough, RMF and Hayward, DC and Wiedemann, U and Forêt, S and Miller, DJ and Ball, EE}, title = {Expression of the neuropeptides RFamide and LWamide during development of the coral Acropora millepora in relation to settlement and metamorphosis.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {56-67}, doi = {10.1016/j.ydbio.2018.11.022}, pmid = {30521809}, issn = {1095-564X}, abstract = {Neuropeptides play critical roles in cnidarian development. However, although they are known to play key roles in settlement and metamorphosis, their temporal and spatial developmental expression has not previously been characterized in any coral. We here describe Acropora millepora LWamide and RFamide and their developmental expression from the time of their first appearance, using in situ hybridization and FMRFamide immunohistochemistry. AmRFamide transcripts first appear in the ectoderm toward the oral end of the planula larva following blastopore closure. This oral bias becomes less apparent as the planula develops. The cell bodies of AmRFamide-expressing cells are centrally located in the ectoderm, with narrow projections to the mesoglea and to the cell surface. As the planula approaches settlement, AmRFamide expression disappears and is undetectable in the newly settled polyp. Expressing cells then gradually reappear as the polyp develops, becoming particularly abundant on the tentacles. AmLWamide transcripts first appear in ectodermal cells of the developing planula, with minimal expression at its two ends. The cell bodies of expressing cells lie just above the mesoglea, in a position distinct from those of AmRFamide-expressing cells, and have a narrow projection extending across the ectoderm to its surface. AmLWamide-expressing cells persist for most of the planula stage, disappearing shortly before settlement, but later than AmRFamide-expressing cells. As is the case with AmRFamide, expressing cells are absent from the polyp immediately after settlement, reappearing later on its oral side. AmLWamide expression lags that of AmRFamide in both its disappearance and reappearance. Antibodies to FMRFamide stain cells in a pattern similar to that of the transcripts, but also cells in areas where there is no expression revealed by in situ hybridization, most notably at the aboral end of the planula and in the adult polyp. Adult polyps have numerous staining cells on the tentacles and oral discs, as well as an immunoreactive nerve ring around the mouth. There are scattered staining cells in the coenosarc between polyps and staining cells are abundant in the mesenterial filaments. The above results are discussed in the context of our knowledge of the behavior of coral planulae at the time of their settlement and metamorphosis. Corals are facing multiple environmental threats, and these results both highlight the need for, and bring us a step closer to, a mechanistic understanding of a process that is critical to their survival.}, } @article {pmid30521808, year = {2019}, author = {Materna, SC and Sinha, T and Barnes, RM and Lammerts van Bueren, K and Black, BL}, title = {Cardiovascular development and survival require Mef2c function in the myocardial but not the endothelial lineage.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {170-177}, doi = {10.1016/j.ydbio.2018.12.002}, pmid = {30521808}, issn = {1095-564X}, support = {R01 HL064658/HL/NHLBI NIH HHS/United States ; R01 HL136182/HL/NHLBI NIH HHS/United States ; }, abstract = {MEF2C is a member of the highly conserved MEF2 family of transcription factors and is a key regulator of cardiovascular development. In mice, Mef2c is expressed in the developing heart and vasculature, including the endothelium. Loss of Mef2c function in germline knockout mice leads to early embryonic demise and profound developmental abnormalities in the cardiovascular system. Previous attempts to uncover the cause of embryonic lethality by specifically disrupting Mef2c function in the heart or vasculature failed to recapitulate the global Mef2c knockout phenotype and instead resulted in relatively minor defects that did not compromise viability or result in significant cardiovascular defects. However, previous studies examined the requirement of Mef2c in the myocardial and endothelial lineages using Cre lines that begin to be expressed after the expression of Mef2c has already commenced. Here, we tested the requirement of Mef2c in the myocardial and endothelial lineages using conditional knockout approaches in mice with Cre lines that deleted Mef2c prior to onset of its expression in embryonic development. We found that deletion of Mef2c in the early myocardial lineage using Nkx2-5Cre resulted in cardiac and vascular abnormalities that were indistinguishable from the defects in the global Mef2c knockout. In contrast, early deletion of Mef2c in the vascular endothelium using an Etv2::Cre line active prior to the onset of Mef2c expression resulted in viable offspring that were indistinguishable from wild type controls with no overt defects in vascular development, despite nearly complete early deletion of Mef2c in the vascular endothelium. Thus, these studies support the idea that the requirement of MEF2C for vascular development is secondary to its requirement in the heart and suggest that the observed failure in vascular remodeling in Mef2c knockout mice results from defective heart function.}, } @article {pmid30521074, year = {2019}, author = {Butka, EG and Freedberg, S}, title = {Population structure leads to male-biased population sex ratios under environmental sex determination.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {99-110}, doi = {10.1111/evo.13653}, pmid = {30521074}, issn = {1558-5646}, abstract = {Spatial structure has been shown to favor female-biased sex allocation, but current theory fails to explain male biases seen in many taxa, particularly those with environmental sex determination (ESD). We present a theory and accompanying individual-based simulation model that demonstrates how population structure leads to male-biased population sex ratios under ESD. Our simulations agree with earlier work showing that the high productivity of female-producing habitats creates a net influx of sex-determining alleles into male-producing habitats, causing larger sex ratio biases, and lower productivity in male-producing environments (Harts et al. 2014). In contrast to previous findings, we show that male-biasing habitats disproportionately impact the global sex ratio, resulting in stable male-biased population sex ratios under ESD. The failure to detect a male bias in earlier work can be attributed to small subpopulation sizes leading to local mate competition, a condition unlikely to be met in most ESD systems. Simulations revealed that consistent male biases are expected over a wide range of population structures, environmental conditions, and genetic architectures of sex determination, with male excesses as large as 30 percent under some conditions. Given the ubiquity of genetic structure in natural populations, we predict that modest, enduring male biased allocation should be common in ESD species, a pattern consistent with reviews of ESD sex ratios.}, } @article {pmid30521052, year = {2018}, author = {Wang, B and Wangkahart, E and Secombes, CJ and Wang, T}, title = {Insights into the evolution of the suppressors of cytokine signalling (SOCS) gene family in vertebrates.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy230}, pmid = {30521052}, issn = {1537-1719}, abstract = {The SOCS family are key negative regulators of cytokine and growth factor signalling. Typically 8-17 SOCS genes are present in vertebrate species and eight known in mammals, classified as type I (SOCS4-7) and type II (CISH and SOCS1-3) SOCS. It was believed that the type II SOCS were expanded through the two rounds of whole genome duplication (1R and 2R WGDs) from a single CISH/SOCS1-3 precursor. Previously 12 genes were identified in rainbow trout but here we report additional 15 loci are present, and confirm 26 of the genes are expressed, giving rainbow trout the largest SOCS gene repertoire identified to date. The discovery of the additional SOCS genes in trout has led to a novel model of SOCS family evolution, whereby the vertebrate SOCS gene family was derived from CISH/SOCS2, SOCS1/SOCS3, SOCS4/5, SOCS6 and SOCS7 ancestors likely present before the two round WGD events. It is also apparent that teleost SOCS2b, SOCS4 and SOCS5b molecules are not true orthologues of mammalian SOCS2, SOCS4 and SOCS5, respectively. The rate of SOCS gene structural changes increased from 2R vertebrates, to 4R rainbow trout, and the genes with structural changes show large differences and low correlation coefficient of expression levels relative to their paralogues, suggesting a role of structural changes in expression and functional diversification. This study has important impacts in the functional prediction and understanding of the SOCS gene family in different vertebrates, and provides a framework for determining how many SOCS genes could be expected in a particular vertebrate species/lineage.}, } @article {pmid30521036, year = {2018}, author = {Beaulieu, JM and O'Meara, BC and Zaretzki, R and Landerer, C and Chai, J and Gilchrist, MA}, title = {Population Genetics Based Phylogenetics Under Stabilizing Selection for an Optimal Amino Acid Sequence: A Nested Modeling Approach.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy222}, pmid = {30521036}, issn = {1537-1719}, abstract = {We present a new phylogenetic approach SelAC (Selection on Amino acids and Codons), whose substitution rates are based on a nested model linking protein expression to population genetics. Unlike simpler codon models which assume a single substitution matrix for all sites, our model more realistically represents the evolution of protein coding DNA under the assumption of consistent, stabilizing selection using cost-benefit approach. This cost-benefit approach allows us generate a set of 20 optimal amino acid specific matrix families using just a handful of parameters and naturally links the strength of stabilizing selection to protein synthesis levels, which we can estimate. Using a yeast dataset of 100 orthologs for 6 taxa, we find SelAC fits the data much better than popular models by 104-105 AICc units. Our results also indicated that nested, mechanistic models better predict observed data patterns highlighting the improvement in biological realism in amino acid sequence evolution that our model provides. Additional parameters estimated by SelAC indicate that a large amount of non-phylogenetic, but biologically meaningful, information can be inferred from exisiting data. For example, SelAC prediction of gene specific protein synthesis rates correlates well with both empirical (r = 0.33-0.48) and other theoretical predictions (r=0.45-0.64) for multiple yeast species. SelAC also provides estimates of the optimal amino acid at each site. Finally, because SelAC is a nested approach based on clearly stated biological assumptions, future modifications, such as including shifts in the optimal amino acid sequence within or across lineages, are possible.}, } @article {pmid30521003, year = {2018}, author = {Vilgalys, T and Rogers, J and Jolly, C and Mukherjee, S and Tung, J}, title = {Evolution of DNA methylation in Papio baboons.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy227}, pmid = {30521003}, issn = {1537-1719}, abstract = {Changes in gene regulation have long been thought to play an important role in primate evolution. However, although a number of studies have compared genome-wide gene expression patterns across primate species, fewer have investigated the gene regulatory mechanisms that underlie such patterns, or the relative contribution of drift versus selection. Here, we profiled genome-scale DNA methylation levels in blood samples from five of the six extant species of the baboon genus Papio (4-14 individuals per species). This radiation presents the opportunity to investigate DNA methylation divergence at both shallow and deeper time scales (380,000 - 1.4 million years). In contrast to studies in human populations, but similar to studies in great apes, DNA methylation profiles clearly mirror genetic and geographic structure. Divergence in DNA methylation proceeds fastest in unannotated regions of the genome and slowest in regions of the genome that are likely more constrained at the sequence level (e.g., gene exons). Both heuristic approaches and Ornstein-Uhlenbeck models suggest that DNA methylation levels at a small set of sites have been affected by positive selection, and that this class is enriched in functionally relevant contexts, including promoters, enhancers, and CpG islands. Our results thus indicate that the rate and distribution of DNA methylation changes across the genome largely mirror genetic structure. However, at some CpG sites, DNA methylation levels themselves may have been a target of positive selection, pointing to loci that could be important in connecting sequence variation to fitness-related traits.}, } @article {pmid30520713, year = {2018}, author = {Whitman, WB and Bull, CT and Busse, HJ and Fournier, PE and Oren, A and Ventura, S}, title = {Request for revision of the Statutes of the International Committee on Systematics of Prokaryotes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003117}, pmid = {30520713}, issn = {1466-5034}, abstract = {At the Valencia Plenary meeting on 7-9 July, 2017, the Working Group on the organization and structure of the ICSP recommended amendment of the Statutes of the ICSP (Dijkshoorn L. Int J Syst Evol Microbiol 2018; 68: 2104-2110). In October 2017, our Executive-Secretary, Lenie Dijkshoorn, sent out a call for participation in this working group, which began work in December, 2017. The members included William B. Whitman, Carolee Bull, Hans-Jürgen Busse, Pierre-Edouard Fournier, Aharon Oren, and Stefano Ventura. During the Winter and Spring, 2018, a large number of revisions were discussed by the working group. In addition, comments were solicited from Dan Brown [Secretary for Subcommittees on Taxonomy], Iain Sutcliffe [Chair ICSP], Fanus Venter [Member at Large, EB-ICSP], and Martha Trujillo [Editor-in-Chief of IJSEM]. The draft Statutes were then presented to the Executive Board [EB] at its online meeting on May 31, 2018. The EB asked that the working group circulate the draft to the members of the ICSP for comments for 45 days and that comments be returned by July 27, 2018. After that time, the working group incorporated additional suggestions before the final submission to IJSEM for publication. According to our current statutes, there will then be a period of 90 days following publication for further deliberation before a vote by the ICSP members.}, } @article {pmid30520710, year = {2018}, author = {Saraf, AG and Dawda, HG and Singh, P}, title = {Desikacharya gen. nov., a phylogenetically distinct genus of Cyanobacteria along with the description of two new species, Desikacharya nostocoides sp. nov. and Desikacharya soli sp. nov., and reclassification of Nostoc thermotolerans to Desikacharya thermotolerans comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003093}, pmid = {30520710}, issn = {1466-5034}, abstract = {Two Nostoc-like strains have been isolated, purified, cultured and identified on the basis of the polyphasic approach using morphological, ecological, molecular and phylogenetic methods. Both strains were found to have morphology similar to the genus Nostoc, but clustered strongly in a group distant from the Nostocsensu stricto clade. Further analysis, using the folded structures of the 16S-23S ITS region revealed strong differences from closely related members of the genus Nostoc. Distinct phylogenetic clustering and strong tree topologies using Bayesian inference, maximum-likelihood and maximum-parsimony methods indicated the need to revisit the taxonomy of the members of this particular clade with a clear need for giving a generic status distinct from the genus Nostoc. In accordance with the International Code of Nomenclature for Algae, Fungi and Plants, the name Desikacharya gen. nov. is proposed for the new genus along with the description of two new species, Desikacharya nostocoides sp. nov. and Desikacharya soli sp. nov., and reclassification of Nostoc thermotolerans to Desikacharya thermotolerans comb. nov.}, } @article {pmid30520011, year = {2019}, author = {Rebolleda-Gómez, M and Travisano, M}, title = {Adaptation, chance, and history in experimental evolution reversals to unicellularity.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {73-83}, doi = {10.1111/evo.13654}, pmid = {30520011}, issn = {1558-5646}, support = {//John Templeton Foundation/ ; 1051115//Division of Environmental Biology/ ; }, abstract = {Evolution is often deemed irreversible. The evolution of complex traits that require many mutations makes their reversal unlikely. Even in simpler traits, reversals might become less likely as neutral or beneficial mutations, with deleterious effects in the ancestral context, become fixed in the novel background. This is especially true in changes that involve large reorganizations of the organism and its interactions with the environment. The evolution of multicellularity involves the reorganization of previously autonomous cells into a more complex organism; despite the complexity of this change, single cells have repeatedly evolved from multicellular ancestors. These repeated reversals to unicellularity undermine the generality of Dollo's law. In this article, we evaluated the dynamics of reversals to unicellularity from recently evolved multicellular phenotypes of the brewers yeast Saccharomyces cerevisae. Even though multicellularity in this system evolved recently, it involves the evolution of new levels of selection. Strong selective pressures against multicellularity lead to rapid reversibility to single cells in all of our replicate lines, whereas counterselection favoring multicellularity led to minimal reductions to the rates of reversal. History and chance played an important role in the tempo and mode of reversibility, highlighting the interplay of deterministic and stochastic events in evolutionary reversals.}, } @article {pmid30519449, year = {2018}, author = {Fraser, D and Haupt, RJ and Andrew Barr, W}, title = {Phylogenetic signal in tooth wear dietary niche proxies: What it means for those in the field.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11363-11367}, pmid = {30519449}, issn = {2045-7758}, abstract = {In response to DeSantis et al., we describe that the presence of phylogenetic signal in tooth wear dietary niche proxies is likely a result of the evolutionary process. We also address their concerns regarding enforcement of the use of phylogenetic comparative methods by editors of ecology and evolution journals.}, } @article {pmid30519448, year = {2018}, author = {DeSantis, L and Fortelius, M and Grine, FE and Janis, C and Kaiser, TM and Merceron, G and Purnell, MA and Schulz-Kornas, E and Saarinen, J and Teaford, M and Ungar, PS and Žliobaitė, I}, title = {The phylogenetic signal in tooth wear: What does it mean?.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11359-11362}, pmid = {30519448}, issn = {2045-7758}, abstract = {A new study by Fraser et al (2018) urges the use of phylogenetic comparative methods, whenever possible, in analyses of mammalian tooth wear. We are concerned about this for two reasons. First, this recommendation may mislead the research community into thinking that phylogenetic signal is an artifact of some sort rather than a fundamental outcome of the evolutionary process. Secondly, this recommendation may set a precedent for editors and reviewers to enforce phylogenetic adjustment where it may unnecessarily weaken or even directionally alter the results, shifting the emphasis of analysis from common patterns manifested by large clades to rare cases.}, } @article {pmid30519447, year = {2018}, author = {Owens, ACS and Lewis, SM}, title = {The impact of artificial light at night on nocturnal insects: A review and synthesis.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11337-11358}, pmid = {30519447}, issn = {2045-7758}, abstract = {In recent decades, advances in lighting technology have precipitated exponential increases in night sky brightness worldwide, raising concerns in the scientific community about the impact of artificial light at night (ALAN) on crepuscular and nocturnal biodiversity. Long-term records show that insect abundance has declined significantly over this time, with worrying implications for terrestrial ecosystems. The majority of investigations into the vulnerability of nocturnal insects to artificial light have focused on the flight-to-light behavior exhibited by select insect families. However, ALAN can affect insects in other ways as well. This review proposes five categories of ALAN impact on nocturnal insects, highlighting past research and identifying key knowledge gaps. We conclude with a summary of relevant literature on bioluminescent fireflies, which emphasizes the unique vulnerability of terrestrial light-based communication systems to artificial illumination. Comprehensive understanding of the ecological impacts of ALAN on diverse nocturnal insect taxa will enable researchers to seek out methods whereby fireflies, moths, and other essential members of the nocturnal ecosystem can coexist with humans on an increasingly urbanized planet.}, } @article {pmid30519446, year = {2018}, author = {Prieto-Ramirez, AM and Pe'er, G and Rödder, D and Henle, K}, title = {Realized niche and microhabitat selection of the eastern green lizard (Lacerta viridis) at the core and periphery of its distribution range.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11322-11336}, pmid = {30519446}, issn = {2045-7758}, abstract = {The available range of habitats and suitable abiotic conditions like temperature and radiation tends to be narrower toward the periphery of the distribution range of species. Peripheral populations of generalist species could then be more specialized and have a smaller and differentiated realized niche (habitat niche in our study) compared to populations at the core. Likewise, patterns of microhabitat selection can differ between periphery and core. In our study, we compared niche size and microhabitat selection among core (Bulgaria) and northern peripheral (Germany, Czech Republic) populations of Lacerta viridis and estimated niche differentiation among regions. We collected data on vegetation structure and abiotic parameters at the microhabitat scale in each region. In order to compare niche size among regions and estimate niche differentiation, we built multidimensional niche hypervolumes. We applied generalized linear mixed models and model averaging, accounting for spatial autocorrelation when necessary, to analyze microhabitat differences among regions and microhabitat selection in each region. Peripheral populations were more specialized, having a smaller niche than core ones, and their niche differed from that in the core (Sørensen overlap in all comparisons <0.3). Microhabitats at the periphery had lower radiation and soil compaction and less structured vegetation. Microhabitat selection at the core depended solely on abiotic parameters, while at the periphery it was defined by only vegetation structure (Czech Republic) or a combination of both, vegetation structure, and abiotic factors (Germany). Thus, peripheral populations seem to compensate for overall harsher climatic conditions by responding to different parameters of the microhabitat compared to core populations. We suggest specific conservation measures for L. virids in each studied region and point out the general implications of a higher specialization degree of peripheral populations in relation to climate change and habitat fragmentation.}, } @article {pmid30519445, year = {2018}, author = {Bessega, C and Pometti, C and López, RP and Larrea-Alcázar, D and Fortunato, RH and Saidman, B and Vilardi, JC}, title = {Genetic diversity and differentiation among Prosopis alba (Leguminosae) populations from dry valleys of Bolivia with different levels of human disturbance and altitude.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11309-11321}, pmid = {30519445}, issn = {2045-7758}, abstract = {The fast expansion of human population around La Paz, Bolivia (3,200-4,100 m.a.s.l.) triggered new suburban settlements in nearby areas in valleys and mountain feet. The white mesquite, Prosopis alba Griseb. (Leguminosae), is a resource (originally used by native communities) that is strongly affected by changes in land use. A gradient in the level of disturbance is found moving away from the La Paz city toward less altitude areas. The main objective of this study was to characterize genetically three P. alba populations with different levels of human disturbance located at different altitudes in Bolivia, in order to provide some guidelines for management and conservation of these species. Based on 10 SSR loci, the populations showed high level of genetic diversity in comparison with other forest species. The population less disturbed and situated at the lowest altitude was the most variable (He = 0.51-0.42), whereas the less variable was the most disturbed and situated at the highest altitude. Heterozygote excess was observed in all populations. Most of genetic diversity (99%) is contained within populations. Genetic differentiation among populations is low (1%), suggesting low gene flow among populations. No evidence of recent bottlenecks events was detected. The estimates of the effective population size were low in all populations. The results are in agreement with the hypothesis that genetic diversity is reduced by the impact of anthropic disturbance in the population located at higher altitude in comparison with the lightly disturbed situated at lower altitude and farther from urban settlements.}, } @article {pmid30519444, year = {2018}, author = {Vanbianchi, C and Gaines, WL and Murphy, MA and Hodges, KE}, title = {Navigating fragmented landscapes: Canada lynx brave poor quality habitats while traveling.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11293-11308}, pmid = {30519444}, issn = {2045-7758}, abstract = {Anthropogenic and natural habitat fragmentation inhibit movement of animals through landscapes. An important challenge for connectivity conservation is determining which conditions facilitate or limit movements, so that these areas can be prioritized for protection or restoration. We examine Canada lynx Lynx canadensis habitat connectivity in the fragmented North Cascade Mountains of Washington, as an example of a highly mobile species that is specialized both on prey and in habitat needs. We identify lynx Habitat Concentration Areas based on Core Habitat Models, parameterize resistance surfaces from our Matrix Habitat Model, and develop linkages of habitat lynx use to move between patches of high quality habitat. We identify a number of linkages for lynx comprised of habitat conditions that differed from high quality core patches identified from our habitat modeling. Radio-locations from lynx confirm lower-quality habitats of low resistance to movement were used by traveling lynx. Our results thus suggest traveling lynx do indeed use a much broader range of habitats than do lynx moving within core areas. For lynx in the North Cascades, our results show that maintaining connectivity will require preserving habitats and linkages that would previously have been deemed unsuitable for lynx. Maintaining connectivity for lynx is particularly important given the many recent large wildfires in this region that have reduced the number of mature forest stands that form prime habitat for lynx. Policy implications. Our results strongly suggest that habitat connectivity models should be based on empirical information of animal location data and focused on matrix habitat analysis. Traveling predators use a wide suite of habitats, resulting in more and broader linkage zones that should inform conservation efforts. Failure to identify these areas of functional connectivity could result in the oversight of usable linkage zones, leaving them without protection and vulnerable to degradation.}, } @article {pmid30519443, year = {2018}, author = {Rohfritsch, A and Galan, M and Gautier, M and Gharbi, K and Olsson, G and Gschloessl, B and Zeimes, C and VanWambeke, S and Vitalis, R and Charbonnel, N}, title = {Preliminary insights into the genetics of bank vole tolerance to Puumala hantavirus in Sweden.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11273-11292}, pmid = {30519443}, issn = {2045-7758}, abstract = {Natural reservoirs of zoonotic pathogens generally seem to be capable of tolerating infections. Tolerance and its underlying mechanisms remain difficult to assess using experiments or wildlife surveys. High-throughput sequencing technologies give the opportunity to investigate the genetic bases of tolerance, and the variability of its mechanisms in natural populations. In particular, population genomics may provide preliminary insights into the genes shaping tolerance and potentially influencing epidemiological dynamics. Here, we addressed these questions in the bank vole Myodes glareolus, the specific asymptomatic reservoir host of Puumala hantavirus (PUUV), which causes nephropathia epidemica (NE) in humans. Despite the continuous spatial distribution of M. glareolus in Sweden, NE is endemic to the northern part of the country. Northern bank vole populations in Sweden might exhibit tolerance strategies as a result of coadaptation with PUUV. This may favor the circulation and maintenance of PUUV and lead to high spatial risk of NE in northern Sweden. We performed a genome-scan study to detect signatures of selection potentially correlated with spatial variations in tolerance to PUUV. We analyzed six bank vole populations from Sweden, sampled from northern NE-endemic to southern NE-free areas. We combined candidate gene analyses (Tlr4, Tlr7, and Mx2 genes) and high-throughput sequencing of restriction site-associated DNA (RAD) markers. Outlier loci showed high levels of genetic differentiation and significant associations with environmental data including variations in the regional number of NE human cases. Among the 108 outliers that matched to mouse protein-coding genes, 14 corresponded to immune-related genes. The main biological pathways found to be significantly enriched corresponded to immune processes and responses to hantavirus, including the regulation of cytokine productions, TLR cascades, and IL-7, VEGF, and JAK-STAT signaling. In the future, genome-scan replicates and functional experimentations should enable to assess the role of these biological pathways in M. glareolus tolerance to PUUV.}, } @article {pmid30519442, year = {2018}, author = {Di Lucchio, LM and Fensholt, R and Markussen, B and Ræbild, A}, title = {Leaf phenology of thirteen African origins of baobab (Adansonia digitata (L.)) as influenced by daylength and water availability.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11261-11272}, pmid = {30519442}, issn = {2045-7758}, abstract = {Water availability is often described as one of the main drivers of phenology of tropical dry forests but experimental studies to identify the cues triggering phenological changes are few. In a greenhouse trial, we exposed seedlings of thirteen origins, seven from West and six from East Africa, respectively, of Adansonia digitata L.(baobab) to a well-watered control treatment and a water withholding treatment in combination with exposure to three different daylengths (11.5, 12.0, and 12.5 hr). Responses were measured in terms of meristematic activity, number of leaves, and height growth followed over 6.5 months. Multi-level mixed-effects statistical models were used to analyze how environmental and inter-population variables affected phenological behavior. Flushing was influenced by the daylength with the lowest degree of meristematic activity observed in the short daylength treatment. Daylength also influenced the number of leaves through an interaction with the water regime. The water regime influenced all variables through interactions with the origins. Seedlings subjected to water stress had higher meristematic activity, but initially lower numbers of leaves than continuously watered plants. Height growth in continuously watered plants was fastest or at par with water-stressed plants, depending on the origin. Origins from West Africa tended to have higher meristematic activity and their phenology was found to be less influenced by water withholding than East African origins. There were no signs of significant differences between origins in their response to photoperiod. In conclusion, baobab seedlings show opportunistic behavior, setting leaves when water is available, but larger activity is found when days are long. We discuss the results in terms of triggering factors for baobab phenology and adaptation to specific environmental conditions at the site of origins.}, } @article {pmid30519441, year = {2018}, author = {Van Dooren, TJM and Varela-Lasheras, I}, title = {Embryonal life histories: Desiccation plasticity and diapause in the Argentinean pearlfish Austrolebias bellottii.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11246-11260}, pmid = {30519441}, issn = {2045-7758}, abstract = {Embryos of annual killifish diapause in soil egg banks while ponds are dry. Their rates of development and survival in different developmental stages determine the numbers and stages of embryos at rewetting. In the Argentinean pearlfish Austrolebias bellottii, we investigated plasticity for desiccation in such embryonal life history components across phases of mild desiccation and rewetting and also effects of life history on hatching. In comparison with nonannuals, our data suggest that incidences of diapause have become relatively independent of the occurrence of desiccation, as if they have become genetically assimilated. We found limited survival effects of desiccation, limited developmental delays, and an acceleration of development into the prehatching stage. This response can be adaptive when desiccation informs that an opportunity to hatch approaches. Embryos arrest development in the prehatching stage (diapause DIII) or in the dispersed-cell phase (diapause DI). Parental pair variation in rates of development and survival in the earliest developmental stages affects the fraction of embryos that are in DI at rewetting and the number surviving. Given such effects on life history fitness components, rates during embryonal development seem "visible" to selection and the developmental system can thus adapt when pair variation contains a heritable component. In agreement with expectations for the presence of diversified bet-hedging, some embryos hatched and others not in over half of the clutches with several developed embryos at the moment of rewetting. Hatching probabilities increased for eggs produced later in the experiment, and they increased when embryos were rewetted a second time after two months. This response is opposite of what is expected when age-dependent hatching would be adapted to exploit opportunities for completing another generation before the dry season.}, } @article {pmid30519440, year = {2018}, author = {Gaskett, AC and Gallagher, RV}, title = {Orchid diversity: Spatial and climatic patterns from herbarium records.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11235-11245}, pmid = {30519440}, issn = {2045-7758}, abstract = {Aim: We test for spatial and climatic patterns of diversification in the Orchidaceae, an angiosperm family characterized by high levels of species diversity and rarity. Globally, does orchid diversity correlate with land area? In Australia, does diversity correlate with herbarium collecting effort, range size, or climate niche breadth? Where are Australia's orchids distributed spatially, in protected areas, and in climate space?

Location: Global, then Australia.

Methods: We compared orchid diversity with land area for continents and recognized orchid diversity hotspots. Then, we used cleaned herbarium records to compare collecting effort (for Australian Orchidaceae vs. all other plant families, and also among orchid genera). Spatial and climate distributions were mapped to determine orchids' coverage in the protected area network, range sizes, and niche breadths.

Results: Globally, orchid diversity does not correlate with land area (depauperate regions are the subantarctic: 10 species, and northern North America: 394 species). Australian herbarium records and collecting effort generally reflect orchid species diversity (1,583 spp.), range sizes, and niche breadths. Orchids are restricted to 13% of Australia's landmass with 211 species absent from any protected areas. Species richness is the greatest in three biomes with high general biodiversity: Temperate (especially southwest and southeast Australia), Tropical, and Subtropical (coastal northern Queensland). Absence from the Desert is consistent with our realized climate niche-orchids avoid high temperature/low rainfall environments. Orchids have narrower range sizes than nonorchid species. Highly diverse orchid genera have narrower rainfall breadths than less diverse genera.

Main conclusions: Herbarium data are adequate for testing hypotheses about Australian orchids. Distribution is likely driven by environmental factors. In contrast, diversification did not correlate with increases in range size, rainfall, or temperature breadths, suggesting speciation does not occur via invasion and local adaptation to new habitats. Instead, diversification may rely on access to extensive obligate symbioses with mycorrhizae and/or pollinators.}, } @article {pmid30519439, year = {2018}, author = {Milanesi, P and Caniglia, R and Fabbri, E and Puopolo, F and Galaverni, M and Holderegger, R}, title = {Combining Bayesian genetic clustering and ecological niche modeling: Insights into wolf intraspecific genetic structure.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11224-11234}, pmid = {30519439}, issn = {2045-7758}, abstract = {The distribution of intraspecific genetic variation and how it relates to environmental factors is of increasing interest to researchers in macroecology and biogeography. Recent studies investigated the relationships between the environment and patterns of intraspecific genetic variation across species ranges but only few rigorously tested the relation between genetic groups and their ecological niches. We quantified the relationship of genetic differentiation (FST) and the overlap of ecological niches (as measured by n-dimensional hypervolumes) among genetic groups resulting from spatial Bayesian genetic clustering in the wolf (Canis lupus) in the Italian peninsula. Within the Italian wolf population, four genetic clusters were detected, and these clusters showed different ecological niches. Moreover, different wolf clusters were significantly related to differences in land cover and human disturbance features. Such differences in the ecological niches of genetic clusters should be interpreted in light of neutral processes that hinder movement, dispersal, and gene flow among the genetic clusters, in order to not prematurely assume any selective or adaptive processes. In the present study, we found that both the plasticity of wolves-a habitat generalist-to cope with different environmental conditions and the occurrence of barriers that limit gene flow lead to the formation of genetic intraspecific genetic clusters and their distinct ecological niches.}, } @article {pmid30519438, year = {2018}, author = {Grinath, JB}, title = {Short-term, low-level nitrogen deposition dampens a trophic cascade between bears and plants.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11213-11223}, pmid = {30519438}, issn = {2045-7758}, abstract = {Human activities have substantially increased atmospheric nitrogen (N) deposition in ecosystems worldwide, often leading to higher plant quality for herbivores and greater herbivory. Predators frequently suppress herbivores and indirectly benefit plants via "trophic cascades", and the strength of these interactions can also depend on N availability. However, the evidence for N deposition effects on cascades primarily comes from studies of high-level N deposition. Most terrestrial ecosystems currently receive elevated, but low-level N deposition, and it is unclear whether this subtle N enrichment has any effect on cascades. Here, I asked whether low-level N deposition alters a trophic cascade from black bears to plants in Colorado. In this ecological network, bears indirectly benefit plants by consuming ants and suppressing positive effects of ants on herbivores. Using a three year N enrichment experiment, I assessed changes in this cascade by measuring plant and arthropod responses to simulated N deposition, bear damage to ant nests, and the presence of mutualist herbivores and ants. I found that low-level N enrichment and bears had interacting effects on plant reproduction. In ambient N conditions, bears indirectly increased plant reproduction by causing ant nests to become inactive and suppressing positive ant effects on herbivores that were detrimental for plants. Yet, bear-induced ant nest inactivity had no effect on plant reproduction in N-enriched conditions. When N was added, ants had greater positive effects on herbivores, but herbivores had weak effects on plants, potentially because plants were more resistant to herbivores. Ultimately, the results indicate that N enrichment strengthened resource control of the community and weakened plant-herbivore interactions and the cascade from bears to plants. This study suggests that common rates of low-level N deposition are changing the strength of trophic cascades and may have already altered resource versus consumer control of ecological community structure in many ecosystems.}, } @article {pmid30519437, year = {2018}, author = {Takahashi, K and Ikeyama, Y and Okuhara, I}, title = {Stand dynamics and competition in a mixed forest at the northern distribution limit of evergreen hardwood species.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11199-11212}, pmid = {30519437}, issn = {2045-7758}, abstract = {Tree species of three growth forms (evergreen conifers, deciduous hardwoods, and evergreen hardwoods) codominate at the northern distribution limit of evergreen hardwoods in central Japan. This study examined the stand dynamics and competition during 13 years at a single plot to reveal how three growth forms codominate at the ecotone. Species were characterized as large DBH and low tree density for evergreen conifers, and conversely for evergreen hardwoods. Total basal area increased during the examined period, accompanied with the reduction in tree density (i.e., mortality exceeded the recruitment rate). Mortality increased with time especially for small trees of deciduous hardwoods. The effect of competition among the three growth forms on tree growth was not detected. Species were classified into two axes. Ingrowth and recruitment rates of large evergreen conifers were lower than those of small evergreen hardwoods. The population growth rate was lower in species with greater mortality within each growth form. Deciduous hardwoods showed the highest mortality and lowest population growth rates among the three growth forms. Although the tree-ring analysis revealed that disturbances occurred to some extent, the current disturbance regime would not trigger the regeneration of deciduous hardwoods. This study suggests that negative relations of maximum DBH with ingrowth and recruitment rates contribute to codominance of evergreen conifers and evergreen hardwoods, and more frequent or larger disturbances than at present are necessary for regeneration of deciduous hardwoods.}, } @article {pmid30519436, year = {2018}, author = {Boltovskoy, D and Sylvester, F and Paolucci, EM}, title = {Invasive species denialism: Sorting out facts, beliefs, and definitions.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11190-11198}, pmid = {30519436}, issn = {2045-7758}, abstract = {In the last decades, thousands of investigations confirmed the detrimental effects of species translocated by man outside of their native ranges (nonindigenous species, or NIS). However, results concluding that many NIS have null, neutral, or positive impacts on the biota and on human interests are as common in the scientific literature as those that point at baneful impacts. Recently, several scholars confronted the stand that origin per se is not a reliable indicator of negative effects, suggesting that such conclusions are the expression of scientific denialism, often led by spurious purposes, and that their numbers are increasing. When assessed in the context of the growing interest in introduced species, the proportion of academic publications claiming that NIS pose no threats to the environment and to social and economic interests is extremely low, and has not increased since 1990. The widely prevailing notion that many NIS are effectively or potentially harmful does not conflict with the fact that most have mixed (negative, neutral, and positive) impacts. When based on solid grounds, reports of positive or neutral impacts should not be labeled as manipulative or misleading unless proven otherwise, even if they may hamper interest in- and funding of research and control bioinvasion programs.}, } @article {pmid30519435, year = {2018}, author = {Tang, Y and Jiang, J and Chen, C and Chen, Y and Wu, X}, title = {Rainfall pulse response of carbon fluxes in a temperate grass ecosystem in the semiarid Loess Plateau.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11179-11189}, pmid = {30519435}, issn = {2045-7758}, abstract = {Rainfall pulses can significantly influence carbon cycling in water-limited ecosystems. The magnitude of carbon flux component responses to precipitation may vary depending on precipitation amount and antecedent soil moisture, associated with nonlinear responses of plants and soil microbes. The present study was carried out in a temperate grass ecosystem during 2013-2015 in the semiarid Loess Plateau of China, to examine the response of carbon fluxes to precipitation using the "threshold-delay" model. The unique contribution of environmental variables such as precipitation amount and antecedent soil moisture before rainfall (SWC_antecedent) to carbon fluxes in response to rainfall was also investigated. The lower threshold of effective rainfall was 6.6 mm for gross ecosystem production (GEP), 8.5 mm for net ecosystem production (NEP), and 4.5 mm for ecosystem respiration (RE); and the upper threshold of effective rainfall was 21.4 mm for GEP and NEP, and 16.8 mm for RE. Rainfall amount was positively affected the relative rainfall responses of GEP, NEP, and RE. However, SWC_antecedent at 20 cm soil depth offset the response of GEP to rainfall pulses, and SWC_antecedent at 5 cm soil depth offset the response of NEP and RE to rainfall pulses, with corresponding partial slopes of linear regressions of -0.50, -0.40, and -0.52. These results indicated that NEP was more sensitive to rainfall pulses and RE was more sensitive to SWC_antecedent. These results demonstrate the importance of rainfall events of <10 mm and that the negative effect of SWC_antecedent should also be considered when estimating ecosystem carbon fluxes in this semiarid region.}, } @article {pmid30519434, year = {2018}, author = {Caruso, T and De Vries, FT and Bardgett, RD and Lehmann, J}, title = {Soil organic carbon dynamics matching ecological equilibrium theory.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11169-11178}, pmid = {30519434}, issn = {2045-7758}, abstract = {The persistence of soil organic carbon (SOC) has traditionally been explained as a combination of recalcitrance properties and stabilization processes, which lead to the formation of complex organic compounds. However, recent conceptual advances and experimental evidence challenge this view. Here, we test these conceptual advances using a dynamic equilibrium theory of SOC founded on classic ecological theory. We postulate that the persistence of SOC is an equilibrium point where SOC losses resulting from continuous decomposition and SOC gains due to SOC protection are balanced. We show that we can describe the temporal dynamics of SOC remarkably well (average and median R2 = 0.75) in publicly available SOC time series from experiments that investigated the effects of agricultural practices in arable soils. The predictive power of our simplistic model is not meant to compete with that of current multi-pool SOC models or recent developments that include microbial loops. The simplicity of our analysis can, however, show how the conceptual distinction between the forces that control SOC loss and gain, and their equilibrium, can shed light on SOC dynamics. Specifically, our analysis shows that, regardless of specific mechanisms, the persistence of SOC will depend on the ultimate equilibrium between SOC gains and losses, which may depend on environmental (e.g. temperature) and ecological (e.g. spatially structured microbial activities) factors and the relative roles of these factors. Future experimental studies should quantify these roles to formulate a new generation of SOC dynamics model.}, } @article {pmid30519433, year = {2018}, author = {Walker, LE and Marzluff, JM and Metz, MC and Wirsing, AJ and Moskal, LM and Stahler, DR and Smith, DW}, title = {Population responses of common ravens to reintroduced gray wolves.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11158-11168}, pmid = {30519433}, issn = {2045-7758}, abstract = {Top predators have cascading effects throughout the food web, but their impacts on scavenger abundance are largely unknown. Gray wolves (Canis lupus) provide carrion to a suite of scavenger species, including the common raven (Corvus corax). Ravens are wide-ranging and intelligent omnivores that commonly take advantage of anthropogenic food resources. In areas where they overlap with wolves, however, ravens are numerous and ubiquitous scavengers of wolf-acquired carrion. We aimed to determine whether subsidies provided through wolves are a limiting factor for raven populations in general and how the wolf reintroduction to Yellowstone National Park in 1995-1997 affected raven population abundance and distribution on the Yellowstone's Northern Range specifically. We counted ravens throughout Yellowstone's Northern Range in March from 2009 to 2017 in both human-use areas and wolf habitat. We then used statistics related to the local wolf population and the winter weather conditions to model raven abundance during our study period and predict raven abundance on the Northern Range both before and after the wolf reintroduction. In relatively severe winters with greater snowpack, raven abundance increased in areas of human use and decreased in wolf habitat. When wolves were able to acquire more carrion, however, ravens increased in wolf habitat and decreased in areas with anthropogenic resources. Raven populations prior to the wolf reintroduction were likely more variable and heavily dependent on ungulate winter-kill and hunter-provided carcasses. The wolf recovery in Yellowstone helped stabilize raven populations by providing a regular food supply, regardless of winter severity. This stabilization has important implications for effective land management as wolves recolonize the west and global climate patterns change.}, } @article {pmid30519432, year = {2018}, author = {Ramos, SLF and Dequigiovanni, G and Sebbenn, AM and Lopes, MTG and de Macêdo, JLV and Veasey, EA and Alves-Pereira, A and da Silva, PP and Garcia, JN and Kageyama, PY}, title = {Paternity analysis, pollen flow, and spatial genetic structure of a natural population of Euterpe precatoria in the Brazilian Amazon.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11143-11157}, pmid = {30519432}, issn = {2045-7758}, abstract = {Euterpe precatoria, known as açaí do Amazonas, is a regionally important palm of the Amazon rainforest for the fruit production through extractive agriculture. Little information is available with regard to genetic diversity, gene flow, and spatial genetic structure (SGS) of açaí populations, which are essential for the use, management, and conservation of genetic resources of the species. This research aimed to assess the genetic diversity, inbreeding level, SGS, and gene flow in four ontogenetic stages of a natural E. precatoria population in the Brazilian Amazon, based on 18 microsatellite loci. The study was carried out in a natural population dispersed in an area of about 10 ha. Leaf tissues of 248 plants were mapped and sampled and classified into four ontogenetic stages: reproductive (59), immature (70), young (60), and seedling (59). Genetic diversity indices were high for all ontogenetic stages. The fixation index (F) for all ontogenetic stages was not significantly different from zero, indicating the absence of inbreeding. A significant SGS was found for all ontogenetic stages (68-110 m), indicating seed dispersal over short distances. Paternity analysis detected pollen immigration of 39.1%, a selfing rate of 4.2%, and a mean pollen dispersal distance within the population of 531 m. The results indicate substantial allele input in the population via pollen immigration, contributing to the maintenance of the genetic diversity of the population. However, within a population, the renewal with new progenies selected from seed plants spaced at least 110 m apart is important to avoid collecting seeds from related plants.}, } @article {pmid30519431, year = {2018}, author = {Kirkpatrick, L and Mitchell, SN and Park, KJ}, title = {The metric matters when assessing diversity: Assessing lepidopteran species richness and diversity in two habitats under different disturbance regimes.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11134-11142}, pmid = {30519431}, issn = {2045-7758}, abstract = {How we measure diversity can have important implications for understanding the impacts of anthropogenic pressure on ecosystem processes and functioning. Functional diversity quantifies the range and relative abundance of functional traits within a given community and, as such, may provide a more mechanistic understanding of ecosystems. Here, we use a novel approach to examine how lepidopteran richness and diversity, weighted by species abundance, differ between habitats under different disturbance regimes (highly disturbed non-native plantations and less disturbed broadleaf woodlands), both with and without constraining by similarity due to shared taxonomy or functional traits. Comparisons of diversity between the two habitats differed according to which metric was being used; while species richness was 58% greater in broadleaf woodlands, after accounting for species similarity due to shared functional traits, there was little difference between woodland types under two different disturbance regimes. Functional diversity varied within the landscape but was similar in paired broadleaf and plantation sites, suggesting that landscape rather than local factors drive biotic homogenization in plantation dominated landscapes. The higher richness in broadleaf sites appears to be driven by rare species, which share functional traits with more common species. Moth populations in disturbed, plantation sites represent a reduced subset of moth species compared to broadleaf sites, and may be more vulnerable to disturbance pressures such as clear-felling operations due to low community resilience.}, } @article {pmid30519430, year = {2018}, author = {Cheeseman, AE and Ryan, SJ and Whipps, CM and Cohen, JB}, title = {Competition alters seasonal resource selection and promotes use of invasive shrubs by an imperiled native cottontail.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11122-11133}, pmid = {30519430}, issn = {2045-7758}, abstract = {Many ecosystems face multiple invaders, and interactions among invasive and native species may complicate conservation efforts for imperiled species. Examination of fine-scale resource selection can be used to detect patterns in habitat selection resulting from species interactions and assess the value of specific resources, including invasive plants, to wildlife. We used animal location data with mixed-effects resource selection models to examine seasonal competitive interactions and species-specific selection for forage and cover resources by an imperiled native lagomorph, the New England cottontail Sylvilagus transitionalis and its nonnative competitor, the eastern cottontail S. floridanus in the eastern Hudson Valley, NY. We found evidence that resource selection by New England cottontails depended on the relative prevalence of eastern cottontails to New England cottontails. Where eastern cottontails were less prevalent New England cottontail selected for resources characteristic of early successional shrublands. Where eastern cottontails were more prevalent, New England cottontails selected for resources characteristic of later successional shrublands. New England cottontail use of certain invasive shrubs depended on the prevalence of eastern cottontails relative to New England cottontails, suggesting response to invasive plants is confounded by interactions with a nonnative competitor. Our results further emphasize the need for conservation efforts to consider invasive management within the ecosystem context. We demonstrate the utility of resource selection studies to assist in this regard by exploring competitive interactions in the absence of removal studies, while simultaneously assessing the impact of habitat components such as invasive vegetation on species of conservation concern. Synthesis and applications Resource selection studies can be directly applied to inform ongoing species conservation where multiple invaders are present or where species interactions influence resource selection. Fine-scale assessments of resource selection, similar to those presented here, can be used to selectively manage habitat to benefit desired species within the ecosystem context.}, } @article {pmid30519429, year = {2018}, author = {Root-Bernstein, M and Svenning, JC}, title = {Human paths have positive impacts on plant richness and diversity: A meta-analysis.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11111-11121}, pmid = {30519429}, issn = {2045-7758}, abstract = {We assess the impacts of human paths, trails, and roads on plant species richness and Shannon diversity. Most reviews of this topic have not considered community-level measures and have focused on excessive tourism impacts. We found significant positive effects of paths on plant richness and diversity. The effect size for richness was highest when studies included roads (paved) or trails (unpaved). The effect size found for diversity was highest when studies were in grasslands. We also found experimental designs comparing high levels of path use to low levels of path use, near-to-path versus far-from-path and path-presence versus path-absence comparisons obtained the largest effect sizes. There was no evidence that non-native species explained most increases in species richness or diversity. The effect sizes of human paths on plant communities are comparable in magnitude to those reported for other mammals' disturbance and ecosystem engineering activities.}, } @article {pmid30519428, year = {2018}, author = {Newbury, RK and Hodges, KE}, title = {Regional differences in winter diets of bobcats in their northern range.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11100-11110}, pmid = {30519428}, issn = {2045-7758}, abstract = {When generalist predators have wide geographic ranges, diets may differ dramatically, largely as a result of differing prey communities. Bobcats (Lynx rufus) are widely distributed across southern North America, with their northern range edge occurring in southern Canada and in the northern US states. Within this northern range, bobcats are exposed to cold and snowy winters and a limited number of prey species, conditions that are atypical for most of the range of bobcats. We examined winter diets of bobcats in high elevation and very snowy forests in northwest Montana to determine how these generalist predators managed in these harsh conditions in comparison with elsewhere in the northern range. Bobcats consumed five major prey types: Red squirrels (Tamiasciurus hudsonicus) and Cricetid rodents comprised >78% of the dietary biomass, whereas the larger snowshoe hares (Lepus americanus), deer (Odocoileus spp.), and grouse were consumed much less often. The standardized niche breadth of bobcat diets was 0.29; bobcats from across the northern range also routinely ate multiple prey species, although Eastern bobcats appear to consume more lagomorphs than do Western bobcats. These results indicate that bobcats remain generalists in difficult winter conditions while preying primarily on small-bodied prey, although bobcats have highly variable diets across their northern range.}, } @article {pmid30519427, year = {2018}, author = {Cisneros-de la Cruz, DJ and Martínez-Castillo, J and Herrera-Silveira, J and Yáñez-Espinosa, L and Ortiz-García, M and Us-Santamaria, R and Andrade, JL}, title = {Short-distance barriers affect genetic variability of Rhizophora mangle L. in the Yucatan Peninsula.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11083-11099}, pmid = {30519427}, issn = {2045-7758}, abstract = {The environmental variability at local scale results in different physiognomic types of mangrove forest. However, this variability has never been considered in studies of mangrove genetic variability. This study analyzed the genetic and morphological variability and structure of Rhizophora mangle at regional and local scales in the Yucatan Peninsula. Thirteen mangrove populations (eight scrub and five tall), located in seven sites, were sampled, and their morphological variability and relationship with the availability of phosphorus and salinity were analyzed. The diversity and genetic structure were estimated at different hierarchical levels with nine microsatellites, also Bayesian inference and Principal Coordinates Analysis were used. We found a great morphological variability of R. mangle that responded to local environmental variability and not to the precipitation gradient of the peninsula. The genetic diversity found in the peninsula was greater than that reported for other populations in Mexico and was grouped into two regions: the Gulf of Mexico and the Caribbean Sea. At a local scale, tall and scrub mangroves had significant genetic differentiation suggesting that ecological barriers promote genetic differentiation within sites. These results need to be considered in future population genetic studies and for mangrove management and conservation.}, } @article {pmid30519426, year = {2018}, author = {Tills, O and Truebano, M and Feldmeyer, B and Pfenninger, M and Morgenroth, H and Schell, T and Rundle, SD}, title = {Transcriptomic responses to predator kairomones in embryos of the aquatic snail Radix balthica.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11071-11082}, pmid = {30519426}, issn = {2045-7758}, abstract = {The ability of organisms to respond to predation threat by exhibiting induced defenses is well documented, but studies on the potential mechanistic basis for such responses are scarce. Here, we examine the transcriptomic response to predator kairomones of two functionally distinct developmental stages in embryos of the aquatic snail Radix balthica: E8-the stage at which a range-finding trial indicated that kairomone-induced accelerated growth and development first occurred; and E9-the stage at which embryos switched from ciliary- to crawling-driven locomotion. We tested whether expression profiles were influenced by kairomones and whether this influence varied between stages. We also identified potential candidate genes for investigating mechanisms underpinning induced responses. There were 6,741 differentially expressed transcripts between developmental stages, compared to just five in response to predator kairomones. However, on examination of functional enrichment in the transcripts responding to predator kairomones and adopting a less stringent significance threshold, 206 transcripts were identified relating to muscle function, growth, and development, with this response being greater at the later E9 stage. Furthermore, these transcripts included putative annotations for genes identified as responding to predator kairomones in other taxa, including C1q, lectin, and actin domains. Globally, transcript expression appeared reduced in response to predator kairomones and we hypothesize that this might be a result of metabolic suppression, as has been reported in other taxa in response to predation threat.}, } @article {pmid30519425, year = {2018}, author = {Viljakainen, L and Jurvansuu, J and Holmberg, I and Pamminger, T and Erler, S and Cremer, S}, title = {Social environment affects the transcriptomic response to bacteria in ant queens.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11031-11070}, pmid = {30519425}, issn = {2045-7758}, abstract = {Social insects have evolved enormous capacities to collectively build nests and defend their colonies against both predators and pathogens. The latter is achieved by a combination of individual immune responses and sophisticated collective behavioral and organizational disease defenses, that is, social immunity. We investigated how the presence or absence of these social defense lines affects individual-level immunity in ant queens after bacterial infection. To this end, we injected queens of the ant Linepithema humile with a mix of gram+ and gram- bacteria or a control solution, reared them either with workers or alone and analyzed their gene expression patterns at 2, 4, 8, and 12 hr post-injection, using RNA-seq. This allowed us to test for the effect of bacterial infection, social context, as well as the interaction between the two over the course of infection and raising of an immune response. We found that social isolation per se affected queen gene expression for metabolism genes, but not for immune genes. When infected, queens reared with and without workers up-regulated similar numbers of innate immune genes revealing activation of Toll and Imd signaling pathways and melanization. Interestingly, however, they mostly regulated different genes along the pathways and showed a different pattern of overall gene up-regulation or down-regulation. Hence, we can conclude that the absence of workers does not compromise the onset of an individual immune response by the queens, but that the social environment impacts the route of the individual innate immune responses.}, } @article {pmid30519424, year = {2018}, author = {Feng, P and Liu, Z}, title = {Complex gene expansion of the CYP2D gene subfamily.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11022-11030}, pmid = {30519424}, issn = {2045-7758}, abstract = {Cytochrome P450 (CYP) superfamily genes encode enzymes that play a role in metabolizing endogenous compounds and in detoxifying exogenous chemicals. The CYP2D subfamily is a member of the CYP2 family, and its gene expansion in herbivores is presumably linked with the need to detoxify abundant plant toxins in the diet, which indicates that CYP2D gene expansion is associated with dietary preferences. To test this hypothesis, the dietary information and CYP2D gene number for 73 vertebrates from different taxonomic groups including 22 mammals, 49 birds, 1 reptile, and 1 amphibian were collected, and correlation analysis and ANOVA were conducted. The results showed that most species (45/73) had only one CYP2D gene, despite their different diets, and dietary preferences were not correlated with CYP2D gene numbers. Specifically, the majority of birds and 7 mammals had only 1 CYP2D gene, and the CYP2D gene number of mammals ranged from 1 to 11, irrespective of their feeding habits. Species with a CYP2D gene number ≥5 included carnivores, herbivores, and omnivores. Furthermore, statistical analyses revealed that no significant correlation existed between dietary preferences and CYP2D gene number, and there was no significant CYP2D gene number variation among species with different dietary preferences, regardless of whether all vertebrates or specific lineages were considered. Furthermore, gene dynamics which indicated by gene duplication events and loss events showed that CYP2D gene number variation had no relationship with diet, suggesting that diet was not a driving force of CYP2D gene expansion and that CYP2D gene expansion was more complex than previously recognized.}, } @article {pmid30519423, year = {2018}, author = {Gooliaff, TJ and Hodges, KE}, title = {Measuring agreement among experts in classifying camera images of similar species.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {11009-11021}, pmid = {30519423}, issn = {2045-7758}, abstract = {Camera trapping and solicitation of wildlife images through citizen science have become common tools in ecological research. Such studies collect many wildlife images for which correct species classification is crucial; even low misclassification rates can result in erroneous estimation of the geographic range or habitat use of a species, potentially hindering conservation or management efforts. However, some species are difficult to tell apart, making species classification challenging-but the literature on classification agreement rates among experts remains sparse. Here, we measure agreement among experts in distinguishing between images of two similar congeneric species, bobcats (Lynx rufus) and Canada lynx (Lynx canadensis). We asked experts to classify the species in selected images to test whether the season, background habitat, time of day, and the visible features of each animal (e.g., face, legs, tail) affected agreement among experts about the species in each image. Overall, experts had moderate agreement (Fleiss' kappa = 0.64), but experts had varying levels of agreement depending on these image characteristics. Most images (71%) had ≥1 expert classification of "unknown," and many images (39%) had some experts classify the image as "bobcat" while others classified it as "lynx." Further, experts were inconsistent even with themselves, changing their classifications of numerous images when they were asked to reclassify the same images months later. These results suggest that classification of images by a single expert is unreliable for similar-looking species. Most of the images did obtain a clear majority classification from the experts, although we emphasize that even majority classifications may be incorrect. We recommend that researchers using wildlife images consult multiple species experts to increase confidence in their image classifications of similar sympatric species. Still, when the presence of a species with similar sympatrics must be conclusive, physical or genetic evidence should be required.}, } @article {pmid30519422, year = {2018}, author = {DiBattista, JD and Alfaro, ME and Sorenson, L and Choat, JH and Hobbs, JA and Sinclair-Taylor, TH and Rocha, LA and Chang, J and Luiz, OJ and Cowman, PF and Friedman, M and Berumen, ML}, title = {Ice ages and butterflyfishes: Phylogenomics elucidates the ecological and evolutionary history of reef fishes in an endemism hotspot.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10989-11008}, pmid = {30519422}, issn = {2045-7758}, abstract = {For tropical marine species, hotspots of endemism occur in peripheral areas furthest from the center of diversity, but the evolutionary processes that lead to their origin remain elusive. We test several hypotheses related to the evolution of peripheral endemics by sequencing ultraconserved element (UCE) loci to produce a genome-scale phylogeny of 47 butterflyfish species (family Chaetodontidae) that includes all shallow water butterflyfish from the coastal waters of the Arabian Peninsula (i.e., Red Sea to Arabian Gulf) and their close relatives. Bayesian tree building methods produced a well-resolved phylogeny that elucidated the origins of butterflyfishes in this hotspots of endemism. We show that UCEs, often used to resolve deep evolutionary relationships, represent an important tool to assess the mechanisms underlying recently diverged taxa. Our analyses indicate that unique environmental conditions in the coastal waters of the Arabian Peninsula probably contributed to the formation of endemic butterflyfishes. Older endemic species are also associated with narrow versus broad depth ranges, suggesting that adaptation to deeper coral reefs in this region occurred only recently (<1.75 Ma). Even though deep reef environments were drastically reduced during the extreme low sea level stands of glacial ages, shallow reefs persisted, and as such there was no evidence supporting mass extirpation of fauna in this region.}, } @article {pmid30519421, year = {2018}, author = {Maslo, B and Leu, K and Pover, T and Weston, MA and Schlacher, TA}, title = {Managing birds of conservation concern on sandy shores: How much room for future conservation actions is there?.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10976-10988}, pmid = {30519421}, issn = {2045-7758}, abstract = {Resource limitations often prevent the active management required to maintain habitat quality in protected areas. Because restrictions in access or allowable public activities are the sole conservation measure in these locations, an important question to consider is whether species of conservation concern truly benefit from parcels that are shielded from human disturbance. Here, we assess the conservation benefit of protecting birds from human recreation on over 204 km of sandy beaches by (a) estimating the total area of beach-nesting bird habitat that has been created by conservation protections; (b) quantifying the change in nesting habitat extent should further conservation protections be implemented; and (c) providing data to inform future protected area expansion. We use a maximum entropy species distribution modeling approach to estimate the extent and quality of suitable habitat for four beach-nesting bird species of conservation concern under the existing management regime and compare it to scenarios in which the entire study area is either unprotected of fully protected from human disturbance. Managing humans has dramatic conservation returns for least terns and piping plovers, creating extensive nesting habitat that otherwise would not exist. There is considerable scope for conservation gains, potentially tripling the extent of nesting areas. Expanding conservation footprints for American oystercatchers and black skimmers is predicted to enhance the quality of existing nesting areas. The work demonstrates the utility of modeling changes in habitat suitability to inform protected area expansion on ocean beaches and coastal dunes.}, } @article {pmid30519420, year = {2018}, author = {Holmala, K and Herrero, A and Kopatz, A and Schregel, J and Eiken, HG and Hagen, SB}, title = {Genetic evidence of female kin clusters in a continuous population of a solitary carnivore, the Eurasian lynx.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10964-10975}, pmid = {30519420}, issn = {2045-7758}, abstract = {Large terrestrial carnivores can sometimes display strong family bonds affecting the spatial distribution of related individuals. We studied the spatial genetic relatedness and family structure of female Eurasian lynx, continuously distributed in southern Finland. We hypothesized that closely related females form matrilineal assemblages, clustering together with relatives living in the neighboring areas. We evaluated this hypothesis using tissue samples of 133 legally harvested female lynx (from year 2007 to 2015), genotyped with 23 microsatellite markers, and tested for possible spatial genetic family structure using a combination of Bayesian clustering, spatial autocorrelation, and forensic genetic parentage analysis. The study population had three potential family genetic clusters, with a high degree of admixture and geographic overlap, and showed a weak but significant negative relationship between pairwise genetic and geographic distance. Moreover, parentage analysis indicated that 64% of the females had one or more close relatives (sister, mother, or daughter) within the study population. Individuals identified as close kin consistently assigned to the same putative family genetic cluster. They also were sampled closer geographically than females on average, although variation was large. Our results support the possibility that Eurasian lynx forms matrilineal assemblages, and comparisons with males are now required to further assess this hypothesis.}, } @article {pmid30519419, year = {2018}, author = {Dixon, KM and Cary, GJ and Worboys, GL and Gibbons, P}, title = {The disproportionate importance of long-unburned forests and woodlands for reptiles.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10952-10963}, pmid = {30519419}, issn = {2045-7758}, abstract = {Our understanding of the impacts of time since fire on reptiles remains limited, partly because there are relatively few locations where long-term, spatially explicit fire histories are available. Such information is important given the large proportion of some landscapes that are managed with frequent prescribed fire to meet fuel management objectives. We conducted a space-for-time study across a landscape in southeastern Australia where the known fire history spanned 6 months to at least 96 years. Four methods were used to survey reptiles in 81 forest and woodland sites to investigate how time since fire (TSF), habitat, and environmental variables affect reptile richness, abundance, and composition. We used generalized linear models, generalized linear mixed-effects models, PERMANOVA, and SIMPER to identify relationships between the reptile assemblage (richness, abundance, and composition, respectively) and TSF, habitat, and environmental variables. All three reptile metrics were associated with TSF. Reptile richness and abundance were significantly higher in sites >96 years postfire than younger fire ages (0.5-12 years). Reptile composition at long-unburned sites was dissimilar to sites burned more recently but was similar between sites burned 0.5-2 and 6-12 years prior to sampling. Synthesis and applications. Long-unburned forests and woodlands were disproportionately more important for reptile richness and abundance than areas burned 6 months to 12 years prior to sampling. This is important given that long-unburned areas represent <8% of our study area. Our results therefore suggest that reptiles would benefit from protecting remaining long-unburned areas from fire and transitioning a greater proportion of the study area to long-unburned. However, some compositional differences between the long-unburned sites and sites 0.5-12 years postfire indicate that maintaining a diversity in fire ages is important for conserving reptile diversity.}, } @article {pmid30519418, year = {2018}, author = {Yin, Q and Chen, S and Guo, W and Huang, Y and Huang, Y and Zhou, R and Fan, Q and Liao, W}, title = {Pronounced genetic differentiation in Fokienia hodginsii revealed by simple sequence repeat markers.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10938-10951}, pmid = {30519418}, issn = {2045-7758}, abstract = {Fokienia hodginsii is a Tertiary relict conifer of the monotypic genus Fokienia (Cupressaceae s.l.). Currently, the species is distributed in southern China, northern Vietnam, and northern Laos and listed as a "near threatened" species by the IUCN. In this study, a total of 427 individuals of F. hodginsii were sampled from China and Vietnam to characterize its genetic diversity and population differentiation. Based on the profiles of 12 simple sequence repeat (SSR) markers, we observed a high level of genetic diversity in F. hodginsii at the species level (He =0.635), albeit slightly lower than that of its sister species Chamaecyparis obtusa. Signals of bottleneck events were detected in the populations GXDMS, GXHJ, V-PXB, and V-HB, probably due to Pleistocene glaciations or overexploitation in recent years. Pronounced genetic differentiation (Fst= 0.157) was found in this species. The inbreeding index (Fis = 0.176 ± 0.024) indicated that F. hodginsii has a mixed mating system. Significant correlation was found between the pairwise genetic differentiation and geographic distance (r = 0.882, p = 0.01), suggesting that genetic differentiation among the populations follows the model of isolation by distance (IBD). STRUCTURE analysis and principal coordinate analysis revealed that these populations were divided into four groups: the western China group located mainly in the Yunnan-Guizhou Plateau, the central China group located mostly in the Luoxiao Mountains and Nanling Mountains, the eastern China group located in the Wuyi Mountains and the Vietnam group containing two populations in Vietnam. The different terrains and elevations of populations may be the most likely factors leading to the differentiation between the western China group and the central China group, while the geographic isolation caused by the lack of appropriate habitats may greatly contribute to the differentiation between the central China group and the eastern China group. Based on the results, some conservation suggestions for this species are provided, such as establishing seed orchards and multiple nature reserves.}, } @article {pmid30519417, year = {2018}, author = {Vesterinen, EJ and Puisto, AIE and Blomberg, AS and Lilley, TM}, title = {Table for five, please: Dietary partitioning in boreal bats.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10914-10937}, pmid = {30519417}, issn = {2045-7758}, abstract = {Differences in diet can explain resource partitioning in apparently similar, sympatric species. Here, we analyzed 1,252 fecal droppings from five species (Eptesicus nilssonii, Myotis brandtii, M. daubentonii, M. mystacinus, and Plecotus auritus) to reveal their dietary niches using fecal DNA metabarcoding. We identified nearly 550 prey species in 13 arthropod orders. Two main orders (Diptera and Lepidoptera) formed the majority of the diet for all species, constituting roughly 80%-90% of the diet. All five species had different dietary assemblages. We also found significant differences in the size of prey species between the bat species. Our results on diet composition remain mostly unchanged when using either read counts as a proxy for quantitative diet or presence-absence data, indicating a strong biological pattern. We conclude that although bats share major components in their ecology (nocturnal life style, insectivory, and echolocation), species differ in feeding behavior, suggesting bats may have distinctive evolutionary strategies. Diet analysis helps illuminate life history traits of various species, adding to sparse ecological knowledge, which can be utilized in conservation planning.}, } @article {pmid30519416, year = {2018}, author = {Shuai, F and Yu, S and Lek, S and Li, X}, title = {Habitat effects on intra-species variation in functional morphology: Evidence from freshwater fish.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10902-10913}, pmid = {30519416}, issn = {2045-7758}, abstract = {Biotic-environment interactions have long been considered an important factor in functional phenotype differentiation in organisms. The differentiation processes determining functional phenotypes can reveal important mechanisms yielding differences in specific functions of animal traits in the ecosystem. In the present study, we examined functional morphological variations in relation to increasing geographic altitude. Six fish species were examined for how environment factors affect intra-specific functional morphology in the subtropical Pearl River in southern China. Functional morphology traits revealed variable effects due to geographic elevation, although spatial autocorrelation existed among the species tested. The results showed that high-elevation individuals had a more narrow-bodied morphology, with more flexible maneuvrability when swimming, and more evenly distributed musculature than low-elevation individuals. Low-elevation individuals preyed upon larger food sources than high-elevation individuals in some species. Fish functional morphology was strongly affected by regional environmental factors (such as elevation and water temperature) and physical characteristics of local rivers (such as flow velocity, river fractals, and coefficients of fluvial facies). In addition, the effects of the regional factors were stronger than those of the local factors in the Pearl River. Furthermore, it was found that morphological traits associated with locomotion were primarily effected by the river's physical characteristics. While morphological traits associated with food acquisition were primarily affected by water chemical factors (such as DO, water clarity, NH 4-N concentration, and TDS). These results demonstrated that habitat has an influence on the biological morphology of fish species, which further affects the functioning of the organism within the ecosystem.}, } @article {pmid30519415, year = {2018}, author = {Montgomery, RA and Redilla, KM and Ortiz-Calo, W and Smith, T and Keller, B and Millspaugh, JJ}, title = {Evaluating the individuality of animal-habitat relationships.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10893-10901}, pmid = {30519415}, issn = {2045-7758}, abstract = {Examining the ways in which animals use habitat and select resources to satisfy their life history requirements has important implications for ecology, evolution, and conservation. The advent of radio-tracking in the mid-20th century greatly expanded the scope of animal-habitat modeling. Thereafter, it became common practice to aggregate telemetry data collected on a number of tagged individuals and fit one model describing resource selection at the population level. This convention, however, runs the risk of masking important individuality in the nature of associations between animals and their environment. Here, we investigated the importance of individual variation in animal-habitat relationships via the study of a highly gregarious species. We modeled elk (Cervus elaphus) location data, collected from Global Positioning System (GPS) collars, using Bayesian discrete choice resource selection function (RSF) models. Using a high-performance computing cluster, we batch-processed these models at the level of each individual elk (n = 88) and evaluated the output with respect to: (a) the composition of parameters in the most supported models, (b) the estimates of the parameters featured in the global models, and (c) spatial maps of the predicted relative probabilities of use. We detected considerable individual variation across all three metrics. For instance, the most supported models varied with respect to parameter composition with a range of seven to 17 and an average of 14.4 parameters per individual elk. The estimates of the parameters featured in the global models also varied greatly across individual elk with little conformity detected across age or sex classes. Finally, spatial mapping illustrated stark differences in the predicted relative probabilities of use across individual elk. Our analysis identifies that animal-habitat relationships, even among the most gregarious of species, can be highly variable. We discuss the implications of our results for ecology and present some guiding principles for the development of RSF models at the individual-animal level.}, } @article {pmid30519414, year = {2018}, author = {Davis, AJ and Williams, KE and Snow, NP and Pepin, KM and Piaggio, AJ}, title = {Accounting for observation processes across multiple levels of uncertainty improves inference of species distributions and guides adaptive sampling of environmental DNA.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10879-10892}, pmid = {30519414}, issn = {2045-7758}, abstract = {Understanding factors that influence observation processes is critical for accurate assessment of underlying ecological processes. When indirect methods of detection, such as environmental DNA, are used to determine species presence, additional levels of uncertainty from observation processes need to be accounted for. We conducted a field trial to evaluate observation processes of a terrestrial invasive species (wild pigs- Sus scrofa) from DNA in water bodies. We used a multi-scale occupancy analysis to estimate different levels of observation processes (detection, p): the probability DNA is available per sample (θ), the probability of capturing DNA per extraction (γ), and the probability of amplification per qPCR run (δ). We selected four sites for each of three water body types and collected 10 samples per water body during two months (September and October 2016) in central Texas. Our methodology can be used to guide sampling adaptively to minimize costs while improving inference of species distributions. Using a removal sampling approach was more efficient than pooling samples and was unbiased. Availability of DNA varied by month, was considerably higher when water pH was near neutral, and was higher in ephemeral streams relative to wildlife guzzlers and ponds. To achieve a cumulative detection probability >90% (including availability, capture, and amplification), future studies should collect 20 water samples per site, conduct at least two extractions per sample, and conduct five qPCR replicates per extraction. Accounting for multiple levels of uncertainty of observation processes improved estimation of the ecological processes and provided guidance for future sampling designs.}, } @article {pmid30519413, year = {2018}, author = {Roura, Á and Strugnell, JM and Guerra, Á and González, ÁF and Richardson, AJ}, title = {Small copepods could channel missing carbon through metazoan predation.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10868-10878}, pmid = {30519413}, issn = {2045-7758}, abstract = {Global ecosystem models are essential tools for predicting climate change impacts on marine systems. Modeled biogenic carbon fluxes in the ocean often match measured data poorly and part of this could be because small copepods (<2 mm) are modeled as unicellular feeders grazing on phytoplankton and microzooplankton. The most abundant copepods from a seasonal upwelling region of the Eastern North Atlantic were sorted, and a molecular method was applied to copepod gut contents to evaluate the extent of metazoan predation under two oceanographic conditions, a trophic pathway not accounted for in global models. Scaling up the results obtained herein, based on published field and laboratory estimates, suggests that small copepods could ingest 1.79-27.20 gigatons C/year globally. This ignored metazoan-copepod link could increase current estimates of biogeochemical fluxes (remineralization, respiration, and the biological pump) and export to higher trophic levels by 15.6%-24.4%. It could also account for global discrepancies between measured daily ingestion and copepod metabolic demand/growth. The inclusion of metazoan predation into global models could provide a more realistic role of the copepods in the ocean and if these preliminary data hold true at larger sample sizes and scales, the implications would be substantial at the global scale.}, } @article {pmid30519412, year = {2018}, author = {Kleyheeg, E and Nolet, BA and Otero-Ojea, S and Soons, MB}, title = {A mechanistic assessment of the relationship between gut morphology and endozoochorous seed dispersal by waterfowl.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10857-10867}, pmid = {30519412}, issn = {2045-7758}, abstract = {Many plants and invertebrates rely on internal transport by animals for long-distance dispersal. Their dispersal capacity is greatly influenced by interactions with the animal's digestive tract. Omnivorous birds adjust their digestive tract morphology to seasonally variable diets. We performed feeding trials in waterfowl to unravel how changing organ size, in combination with seed size, affects dispersal potential. We subjected captive mallards to mimics of summer (animal-based), winter (plant-based), and intermediate diets, and analyzed gut passage of seeds before and after the treatment (trials 1 and 2). To test the effect of gut morphology on seed digestion, we measured digestive organ size after euthanasia. Three hours before euthanasia, differently sized seeds were fed to test how seed size affects gut passage by determining their relative position in the digestive tract (trial 3). Trials 1 and 2 showed that intact seed passage was lower in the plant-based than in the animal-based diet group. Retention time changed only within groups, decreasing in the animal-based, and increasing in the plant-based diet group. No post-diet differences in organ size were detected, probably due to large between-individual variation within groups. Digestive tract measures did not explain variation in seed survival or retention time. Trial 3 revealed that small seeds pass the digestive tract rapidly, while large seeds are retained longer, particularly in the gizzard. Differential retention in the gizzard, the section where seeds can be destroyed, is likely why larger seeds have a lower probability to pass the digestive tract intact. Our results confirm that rapid, flexible adaptation to diet shifts affects seed digestion in waterfowl, although we could not conclusively relate this to organ size. Large interindividual variation in digestive efficiency between mallards feeding on the same diet may provide opportunities for seed dispersal in the field throughout the annual cycle.}, } @article {pmid30519411, year = {2018}, author = {Bertoloni Meli, S and Bashey, F}, title = {Trade-off between reproductive and anti-competitor abilities in an insect-parasitic nematode-bacteria symbiosis.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10847-10856}, pmid = {30519411}, issn = {2045-7758}, abstract = {Mutualistic symbionts can provide diverse benefits to their hosts and often supply key trait variation for host adaptation. The bacterial symbionts of entomopathogenic nematodes play a crucial role in successful colonization of and reproduction in the insect host. Additionally, these symbionts can produce a diverse array of antimicrobial compounds to deter within-host competitors. Natural isolates of the symbiont, Xenorhabdus bovienii, show considerable variation in their ability to target sympatric competitors via bacteriocins, which can inhibit the growth of sensitive Xenorhabdus strains. Both the bacteria and its nematode partner have been shown to benefit from bacteriocin production when within-host competition with a sensitive competitor occurs. Despite this benefit, several isolates of Xenorhabdus do not inhibit sympatric strains. To understand how this variation in allelopathy could be maintained, we tested the hypothesis that inhibiting isolates face a reproductive cost in the absence of competition. We tested this hypothesis by examining the reproductive success of inhibiting and non-inhibiting isolates coupled with their natural nematode host in a non-competitive context. We found that nematodes carrying non-inhibitors killed the insect host more rapidly and were more likely to successfully reproduce than nematodes carrying inhibitors. Lower reproductive success of inhibiting isolates was repeatable across nematode generations and across insect host species. However, no difference in insect mortality was observed between inhibiting and non-inhibiting isolates when bacteria were injected into insects without their nematode partners. Our results indicate a trade-off between the competitive and reproductive roles of symbionts, such that inhibiting isolates, which are better in the face of within-host competition, pay a reproductive cost in the absence of competition. Furthermore, our results support the hypothesis that symbiont variation within populations can be maintained through context-dependent fitness benefits conferred to their hosts. As such, our study offers novel insights into the selective forces maintaining variation within a single host-symbiont population and highlights the role of competition in mutualism evolution.}, } @article {pmid30519410, year = {2018}, author = {Sint, D and Guenay, Y and Mayer, R and Traugott, M and Wallinger, C}, title = {The effect of plant identity and mixed feeding on the detection of seed DNA in regurgitates of carabid beetles.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10834-10846}, pmid = {30519410}, issn = {2045-7758}, abstract = {Carabids are abundant in temperate agroecosystems and play a pivotal role as biocontrol agents for weed seed and pest regulation. While there is good knowledge regarding their effects on invertebrate pests, direct evidence for seed predation in the field is missing. Molecular approaches are ideally suited to investigate these feeding interactions; however, the effects of an omnivorous diet, which is characteristic for many carabid species, and seed identity on the detection success of seed DNA has not yet been investigated. In a series of feeding experiments, seeds of six different Central European weed species were fed to beetles of the species Pseudoophonus rufipes, to determine post-feeding seed DNA detection rates and how these are affected by plant identity, meal size, and chemical seed composition. Moreover, we investigated the effect of a mixed diet of seeds and mealworm on prey DNA detection. Four out of six seed species were detectable for up to five days after consumption, and seed species identity significantly affected post-feeding detection rates. Detectability was negatively influenced by protein content and seed mass, whereas oil content and meal size had a positive effect. The mixed diet led to both increased detection rates and post-feeding detection intervals of seed DNA. This suggests that mixed feeding leads to an enhancement of food detection intervals in carabid beetles and that seed identity, their chemical composition, and meal size can affect DNA detection of consumed seeds. These aspects and potential implications of this non-invasive approach are discussed as they can become highly relevant for interpreting field-derived data.}, } @article {pmid30519409, year = {2018}, author = {Šarhanová, P and Pfanzelt, S and Brandt, R and Himmelbach, A and Blattner, FR}, title = {SSR-seq: Genotyping of microsatellites using next-generation sequencing reveals higher level of polymorphism as compared to traditional fragment size scoring.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10817-10833}, pmid = {30519409}, issn = {2045-7758}, abstract = {Microsatellites (or simple sequence repeats, SSR) are widely used markers in population genetics. Traditionally, genotyping was and still is carried out through recording fragment length. Now, next-generation sequencing (NGS) makes it easy to obtain also sequence information for the loci of interest. This avoids misinterpretations that otherwise could arise due to size homoplasy. Here, an NGS strategy is described that allows to genotype hundreds of individuals at many custom-designed SSR loci simultaneously, combining multiplex PCR, barcoding, and Illumina sequencing. We created three different datasets for which alleles were coded according to (a) length of the repetitive region, (b) total fragment length, and (c) sequence identity, in order to evaluate the eventual benefits from having sequence data at hand, not only fragment length data. For each dataset, genetic diversity statistics, as well as FST and RST values, were calculated. The number of alleles per locus, as well as observed and expected heterozygosity, was highest in the sequence identity dataset, because of single-nucleotide polymorphisms and insertions/deletions in the flanking regions of the SSR motif. Size homoplasy was found to be very common, amounting to 44.7%-63.5% (mean over all loci) in the three study species. Thus, the information obtained by next-generation sequencing offers a better resolution than the traditional way of SSR genotyping and allows for more accurate evolutionary interpretations.}, } @article {pmid30519408, year = {2018}, author = {Burmester, EM and Breef-Pilz, A and Lawrence, NF and Kaufman, L and Finnerty, JR and Rotjan, RD}, title = {The impact of autotrophic versus heterotrophic nutritional pathways on colony health and wound recovery in corals.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10805-10816}, pmid = {30519408}, issn = {2045-7758}, abstract = {For animals that harbor photosynthetic symbionts within their tissues, such as corals, the different relative contributions of autotrophy versus heterotrophy to organismal energetic requirements have direct impacts on fitness. This is especially true for facultatively symbiotic corals, where the balance between host-caught and symbiont-produced energy can be altered substantially to meet the variable demands of a shifting environment. In this study, we utilized a temperate coral-algal system (the northern star coral, Astrangia poculata, and its photosynthetic endosymbiont, Symbiodinium psygmophilum) to explore the impacts of nutritional sourcing on the host's health and ability to regenerate experimentally excised polyps. For fed and starved colonies, wound healing and total colony tissue cover were differentially impacted by heterotrophy versus autotrophy. There was an additive impact of positive nutritional and symbiotic states on a coral's ability to initiate healing, but a greater influence of symbiont state on the recovery of lost tissue at the lesion site and complete polyp regeneration. On the other hand, regardless of symbiont state, fed corals maintained a higher overall colony tissue cover, which also enabled more active host behavior (polyp extension) and endosymbiont behavior (photosynthetic ability of Symbiondinium). Overall, we determined that the impact of nutritional state and symbiotic state varied between biological functions, suggesting a diversity in energetic sourcing for each of these processes.}, } @article {pmid30519407, year = {2018}, author = {Bane, MS and Pocock, MJO and James, R}, title = {Effects of model choice, network structure, and interaction strengths on knockout extinction models of ecological robustness.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10794-10804}, pmid = {30519407}, issn = {2045-7758}, abstract = {Analysis of ecological networks is a valuable approach to understanding the vulnerability of systems to disturbance. The tolerance of ecological networks to coextinctions, resulting from sequences of primary extinctions (here termed "knockout extinction models", in contrast with other dynamic approaches), is a widely used tool for modeling network "robustness". Currently, there is an emphasis to increase biological realism in these models, but less attention has been given to the effect of model choices and network structure on robustness measures. Here, we present a suite of knockout extinction models for bipartite ecological networks (specifically plant-pollinator networks) that can all be analyzed on the same terms, enabling us to test the effects of extinction rules, interaction weights, and network structure on robustness. We include two simple ecologically plausible models of propagating extinctions, one new and one adapted from existing models. All models can be used with weighted or binary interaction data. We found that the choice of extinction rules impacts robustness; our two propagating models produce opposing effects in all tests on observed plant-pollinator networks. Adding weights to the interactions tends to amplify the opposing effects and increase the variation in robustness. Variation in robustness is a key feature of these extinction models and is driven by the structural heterogeneity of nodes (specifically, the skewness of the plant degree distribution) in the network. Our analysis therefore reveals the mechanisms and fundamental network properties that drive observed trends in robustness.}, } @article {pmid30519406, year = {2018}, author = {Benvenuti, B and Walsh, J and O'Brien, KM and Kovach, AI}, title = {Plasticity in nesting adaptations of a tidal marsh endemic bird.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10780-10793}, pmid = {30519406}, issn = {2045-7758}, abstract = {If individuals can perceive and manage risks, they may alter their behaviors based on prior experience. This expectation may apply to nest site selection of breeding birds, for which adaptive behavioral responses may enhance fitness. Birds that nest in tidal marshes have adapted to the challenges posed primarily by periodic, monthly tidal flooding and secondarily by predation. We investigated adaptive responses in nesting behavior of the saltmarsh sparrow (Ammospiza caudacutus), an obligate tidal-marsh-breeding bird, using 536 nests monitored across 5 years. Using linear mixed effects models, we tested whether nest characteristics differed among nests that were successful, depredated, or flooded, and we investigated whether females made changes in nest structure and placement according to outcome of their previous nesting attempt. Nest characteristics differed among females with different nest fates. Fledged and depredated nests were built higher in the vegetation and in higher elevation areas of the marsh than those that flooded. Successful nests had more canopy cover and were comprised of a lower proportion of high marsh vegetation (Spartina patens) than those that were flooded or depredated. Females with nests that failed due to flooding constructed subsequent nests higher in the vegetation and at higher elevation than those that were successful in their prior attempt, consistent with a response to previous experience. Eighty-five percent of females renested within the average home range core area distance (77 m), indicating a high degree of nest placement fidelity. Females for which nests were depredated in their prior nesting attempt renested at a greater distance than females for which the previous nesting attempts were successful. Our findings suggest saltmarsh sparrows exhibit plasticity in nesting behavior, which may be important for balancing selective pressures in a dynamic environment. This plasticity, however, is insufficient to enable them to adapt to the increased flooding predicted with sea-level rise.}, } @article {pmid30519405, year = {2018}, author = {Salas-Eljatib, C and Weiskittel, AR}, title = {Evaluation of modeling strategies for assessing self-thinning behavior and carrying capacity.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10768-10779}, pmid = {30519405}, issn = {2045-7758}, abstract = {Self-thinning and site maximum carrying capacity are key concepts for understanding and predicting ecosystem dynamics as they represent the outcome of several fundamental ecological processes (e.g., mortality and growth). Relationships are often derived using alternative modeling strategies, depending on the statistical approach, model formulation, and underlying data with unclear implications of these various assumptions. In this analysis, the influence of contrasting modeling strategies for estimating the self-thinning relationship and maximum carrying capacity in long-term, permanent plot data (n = 130) from the mixed Nothofagus forests in southern Chile was assessed and compared. Seven contrasting modeling strategies were used including ordinary least squares, quantile, and nonlinear regression that were formulated based on static (no remeasurements) or dynamic data (with remeasurements). Statistically distinct differences among these seven approaches were identified with mean maximum carrying capacity ranging from 1,050 to 1,912 stems/ha depending on the approach. The population-level static approach based on quantile regression produced an estimate closest to the overall mean with site-level carrying capacity depending on tree species diversity and climate. Synthesis and applications. Overall, the findings highlight strong variability within and between contrasting methods of determining self-thinning and site maximum carry capacity, which may influence ecological inferences.}, } @article {pmid30519404, year = {2018}, author = {Hillaert, J and Hovestadt, T and Vandegehuchte, ML and Bonte, D}, title = {Size-dependent movement explains why bigger is better in fragmented landscapes.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10754-10767}, pmid = {30519404}, issn = {2045-7758}, abstract = {Body size is a fundamental trait known to allometrically scale with metabolic rate and therefore a key determinant of individual development, life history, and consequently fitness. In spatially structured environments, movement is an equally important driver of fitness. Because movement is tightly coupled with body size, we expect habitat fragmentation to induce a strong selection pressure on size variation across and within species. Changes in body size distributions are then, in turn, expected to alter food web dynamics. However, no consensus has been reached on how spatial isolation and resource growth affect consumer body size distributions. Our aim was to investigate how these two factors shape the body size distribution of consumers under scenarios of size-dependent and size-independent consumer movement by applying a mechanistic, individual-based resource-consumer model. We also assessed the consequences of altered body size distributions for important ecosystem traits such as resource abundance and consumer stability. Finally, we determined those factors that explain most variation in size distributions. We demonstrate that decreasing connectivity and resource growth select for communities (or populations) consisting of larger species (or individuals) due to strong selection for the ability to move over longer distances if the movement is size-dependent. When including size-dependent movement, intermediate levels of connectivity result in increases in local size diversity. Due to this elevated functional diversity, resource uptake is maximized at the metapopulation or metacommunity level. At these intermediate levels of connectivity, size-dependent movement explains most of the observed variation in size distributions. Interestingly, local and spatial stability of consumer biomass is lowest when isolation and resource growth are high. Finally, we highlight that size-dependent movement is of vital importance for the survival of populations or communities within highly fragmented landscapes. Our results demonstrate that considering size-dependent movement is essential to understand how habitat fragmentation and resource growth shape body size distributions-and the resulting metapopulation or metacommunity dynamics-of consumers.}, } @article {pmid30519403, year = {2018}, author = {Bolin, LG and Benning, JW and Moeller, DA}, title = {Mycorrhizal interactions do not influence plant-herbivore interactions in populations of Clarkia xantiana ssp. xantiana spanning from center to margin of the geographic range.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10743-10753}, pmid = {30519403}, issn = {2045-7758}, abstract = {Multispecies interactions can be important to the expression of phenotypes and in determining patterns of individual fitness in nature. Many plants engage in symbiosis with arbuscular mycorrhizal fungi (AMF), but the extent to which AMF modulate other species interactions remains poorly understood. We examined multispecies interactions among plants, AMF, and insect herbivores under drought stress using a greenhouse experiment and herbivore choice assays. The experiment included six populations of Clarkia xantiana (Onagraceae), which span a complex environmental gradient in the Southern Sierra Nevada of California. Clarkia xantiana's developing fruits are commonly attacked by grasshoppers at the end of the growing season, and the frequency of attack is more common in populations from the range center than range margin. We found that AMF negatively influenced all metrics of plant growth and reproduction across all populations, presumably because plants supplied carbon to AMF but did not benefit substantially from resources potentially supplied by the AMF. The fruits of plants infected with AMF did not differ from those without AMF in their resistance to grasshoppers. There was significant variation among populations in damage from herbivores but did not reflect the center-to-margin pattern of herbivory observed in the field. In sum, our results do not support the view that AMF interactions modulate plant-herbivore interactions in this system.}, } @article {pmid30519402, year = {2018}, author = {Cotterill, GG and Cross, PC and Middleton, AD and Rogerson, JD and Scurlock, BM and du Toit, JT}, title = {Hidden cost of disease in a free-ranging ungulate: brucellosis reduces mid-winter pregnancy in elk.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10733-10742}, pmid = {30519402}, issn = {2045-7758}, abstract = {Demonstrating disease impacts on the vital rates of free-ranging mammalian hosts typically requires intensive, long-term study. Evidence for chronic pathogens affecting reproduction but not survival is rare, but has the potential for wide-ranging effects. Accurately quantifying disease-associated reductions in fecundity is important for advancing theory, generating accurate predictive models, and achieving effective management. We investigated the impacts of brucellosis (Brucella abortus) on elk (Cervus canadensis) productivity using serological data from over 6,000 captures since 1990 in the Greater Yellowstone Ecosystem, USA. Over 1,000 of these records included known age and pregnancy status. Using Bayesian multilevel models, we estimated the age-specific pregnancy probabilities of exposed and naïve elk. We then used repeat-capture data to investigate the full effects of the disease on life history. Brucellosis exposure reduced pregnancy rates of elk captured in mid- and late-winter. In an average year, we found 60% of exposed 2-year-old elk were pregnant compared to 91% of their naïve counterparts (a 31 percentage point reduction, 89% HPDI = 20%-42%), whereas exposed 3- to 9-year-olds were 7 percentage points less likely to be pregnant than naïve elk of their same age (89% HPDI = 2%-11%). We found these reduced rates of pregnancy to be independent from disease-induced abortions, which afflict a portion of exposed elk. We estimate that the combination of reduced pregnancy by mid-winter and the abortions following mid-winter reduces the reproductive output of exposed female elk by 24%, which affects population dynamics to a similar extent as severe winters or droughts. Exposing hidden reproductive costs of disease is essential to avoid conflating them with the effects of climate and predation. Such reproductive costs cause complex population dynamics, and the magnitude of the effect we found should drive a strong selection gradient if there is heritable resistance.}, } @article {pmid30519401, year = {2018}, author = {Koch, RE and Phillips, JM and Camus, MF and Dowling, DK}, title = {Maternal age effects on fecundity and offspring egg-to-adult viability are not affected by mitochondrial haplotype.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10722-10732}, pmid = {30519401}, issn = {2045-7758}, abstract = {While numerous studies have demonstrated that mitochondrial genetic variation can shape organismal phenotype, the level of contribution the mitochondrial genotype makes to life-history phenotype across the life course remains unknown. Furthermore, a clear technical bias has emerged in studies of mitochondrial effects on reproduction, with many studies conducted on males, but few on females. Here, we apply a classic prediction of the evolutionary theory of aging to the mitochondrial genome, predicting the declining force of natural selection with age will have facilitated the accumulation of mtDNA mutations that confer late-life effects on female reproductive performance. This should lead to increased levels of mitochondrial genetic variation on reproduction at later-life stages. We tested this hypothesis using thirteen strains of Drosophila melanogaster that each possessed a different mitochondrial haplotype in an otherwise standard nuclear genetic background. We measured fecundity and egg-to-adult viability of females over five different age classes ranging from early to late life and quantified the survival of females throughout this time period. We found no significant variation across mitochondrial haplotypes for the reproductive traits, and no mitochondrial effect on the slope of decline in these traits with increasing age. However, we observed that flies that died earlier in the experiment experienced steeper declines in the reproductive traits prior to death, and we also identified maternal and grandparental age effects on the measured traits. These results suggest the mitochondrial variation does not make a key contribution to shaping the reproductive performance of females.}, } @article {pmid30519400, year = {2018}, author = {Claireaux, M and Jørgensen, C and Enberg, K}, title = {Evolutionary effects of fishing gear on foraging behavior and life-history traits.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10711-10721}, pmid = {30519400}, issn = {2045-7758}, abstract = {Fishing gears are designed to exploit the natural behaviors of fish, and the concern that fishing may cause evolution of behavioral traits has been receiving increasing attention. The first intuitive expectation is that fishing causes evolution toward reduced boldness because it selectively removes actively foraging individuals due to their higher encounter rate and vulnerability to typical gear. However, life-history theory predicts that fishing, through shortened life span, favors accelerated life histories, potentially leading to increased foraging and its frequent correlate, boldness. Additionally, individuals with accelerated life histories mature younger and at a smaller size and therefore spend more of their life at a smaller size where mortality is higher. This life-history evolution may prohibit increases in risk-taking behavior and boldness, thus selecting for reduced risk-taking and boldness. Here, we aim to clarify which of these three selective patterns ends up being dominant. We study how behavior-selective fishing affects the optimal behavioral and life-history traits using a state-dependent dynamic programming model. Different gear types were modeled as being selective for foraging or hiding/resting individuals along a continuous axis, including unselective fishing. Compared with unselective harvesting, gears targeting hiding/resting individuals led toward evolution of increased foraging rates and elevated natural mortality rate, while targeting foraging individuals led to evolution of decreased foraging rates and lower natural mortality rate. Interestingly, changes were predicted for traits difficult to observe in the wild (natural mortality and behavior) whereas the more regularly observed traits (length-at-age, age at maturity, and reproductive investment) showed only little sensitivity to the behavioral selectivity.}, } @article {pmid30519399, year = {2018}, author = {Villabona-Arenas, CJ and Ayouba, A and Esteban, A and D'arc, M and Mpoudi Ngole, E and Peeters, M}, title = {Noninvasive western lowland gorilla's health monitoring: A decade of simian immunodeficiency virus surveillance in southern Cameroon.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10698-10710}, pmid = {30519399}, issn = {2045-7758}, abstract = {Simian immunodeficiency virus (SIVgor) causes persistent infection in critically endangered western lowland gorillas (Gorilla gorilla gorilla) from west central Africa. SIVgor is closely related to chimpanzee and human immunodeficiency viruses (SIVcpz and HIV-1, respectively). We established a noninvasive method that does not interfere with gorillas' natural behaviour to provide wildlife pathogen surveillance and health monitoring for conservation. A total of 1,665 geo-referenced fecal samples were collected at regular intervals from February 2006 to December 2014 (123 sampling days) in the Campo-Ma'an National Park (southwest Cameroon). Host genotyping was performed using microsatellite markers, SIVgor infection was identified by serology and genetic amplification was attempted on seropositive individuals. We identified at least 125 distinct gorillas, 50 were resampled (observed 3.5 times in average) and 38 were SIVgor+ (seven individuals were seroconverters). Six groups of gorillas were identified based on the overlapping occurrence of individuals with apparent high rates of gene flow. We obtained SIVgor genetic sequences from 25 of 38 seropositive genotyped gorillas and showed that the virus follows exponential growth dynamics under a strict molecular clock. Different groups shared SIVgor lineages demonstrating intergroup viral spread and recapture of positive individuals illustrated intra-host viral evolution. Relatedness and relationship genetic analysis of gorillas together with Bayesian phylogenetic inference of SIVgor provided evidence suggestive of vertical transmission. In conclusion, we provided insights into gorilla social dynamics and SIVgor evolution and emphasized the utility of noninvasive sampling to study wildlife health populations. These findings contribute to prospective planning for better monitoring and conservation.}, } @article {pmid30519398, year = {2018}, author = {Fagundes, M and Xavier, RCF and Faria, ML and Lopes, LGO and Cuevas-Reyes, P and Reis-Junior, R}, title = {Plant phenological asynchrony and community structure of gall-inducing insects associated with a tropical tree species.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10687-10697}, pmid = {30519398}, issn = {2045-7758}, abstract = {The dynamics of occurrence of target organs in plant populations produces windows of opportunity that directly and indirectly affect the structure of herbivore communities. However, mechanisms that drive herbivore specialization between resource patches are still poorly known. In this study, we tested three hypotheses related to variation in host plant phenology and community structure (i.e., composition, richness, and abundance) of gall-forming species: (a) plants with early leaf-flushing in the season will have greater vegetative growth and high contents of secondary chemical compounds; (b) gall-inducing insect community structure changes among temporary resource patches of the host; and (c) interspecific competition is a probable mechanism that drives gall-inducing insect community structure on Copaifera langsdorffii. We monitored daily a total of 102 individuals of the super-host C. langsdorffii from August 2012 to May 2013, to characterize the leaf flushing time of each host plant. The leaf flushing time had a positive relationship with the number of folioles per branch and a negative relationship with branch growth. We sampled a total of 4,906 galls belonging to 24 gall-inducing insect species from 102 individuals of C. langsdorffii. In spite of some gall-inducing species presented high abundance on early leaf-flushing plants, direct and indirect effects of plant phenology on galling insect abundance was species dependent. At the community level, our study revealed that the quality and quantity of plant resources did not affect the richness and abundance of gall-inducing insects associated with C. langsdorffii. However, the richness and composition of gall-inducing species varied according to the variation in leaf flushing time of the host plant. The results of null model analysis showed that galls co-occurrence on C. langsdorffii trees differ more than expected by chance and that interspecific competition can be one potential mechanism structuring this gall-inducing insect community.}, } @article {pmid30519397, year = {2018}, author = {Mu, W and Liu, J and Zhang, H}, title = {The first complete mitochondrial genome of the Mariana Trench Freyastera benthophila (Asteroidea: Brisingida: Brisingidae) allows insights into the deep-sea adaptive evolution of Brisingida.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10673-10686}, pmid = {30519397}, issn = {2045-7758}, abstract = {Starfish (phylum Echinodermata) are ecologically important and diverse members of marine ecosystems in all of the world's oceans, from the shallow water to the hadal zone. The deep sea is recognized as an extremely harsh environment on earth. In this study, we present the mitochondrial genome sequence of Mariana Trench starfish Freyastera benthophila, and this study is the first to explore in detail the mitochondrial genome of a deep-sea member of the order Brisingida. Similar to other starfish, it contained 13 protein-coding genes, two ribosomal RNA genes, and 22 transfer RNA genes (duplication of two tRNAs: trnL and trnS). Twenty-two of these genes are encoded on the positive strand, while the other 15 are encoded on the negative strand. The gene arrangement was identical to those of sequenced starfish. Phylogenetic analysis showed the deep-sea Brisingida as a sister taxon to the traditional members of the Asteriidae. Positive selection analysis indicated that five residues (8 N and 16 I in atp8, 47 D and 196 V in nad2, 599 N in nad5) were positively selected sites with high posterior probabilities. Compared these features with shallow sea starfish, we predict that variation specifically in atp8, nad2, and nad5 may play an important role in F. benthophila's adaptation to deep-sea environment.}, } @article {pmid30519396, year = {2018}, author = {Chabot, AA and Hobson, KA and Van Wilgenburg, SL and Pérez, GE and Lougheed, SC}, title = {Migratory connectivity in the Loggerhead Shrike (Lanius ludovicianus).}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10662-10672}, pmid = {30519396}, issn = {2045-7758}, abstract = {Aim: We combine genetic and stable isotope data to quantify migration patterns in Loggerhead Shrike (Lanius ludovicianus), a species of conservation concern in North America, to assess how connectivity differs and impacts population evolution, ecology, and conservation.

Location: We sampled shrikes across the majority of their nonbreeding range, from the Atlantic Coast to the western United States east of the Rocky Mountains and throughout Mexico.

Methods: Our study used a Bayesian framework using δ2Hf from a breeding season origin feather and nuclear genetic microsatellite markers to distinguish between co-occurring migratory and nonmigratory individuals on the wintering grounds and, for migrants, to assign individuals to a breeding ground origin and genetic group.

Results: Migratory shrikes were present throughout the nonbreeding range but the proportion differed among sample areas. Four main wintering areas were identified. Connectivity ranged from weakly negative in birds wintering on the Atlantic Coast to strongly positive between wintering grounds in the southwestern United States and Mexico and northwestern breeding populations. Connectivity was weakest in L. l. migrans, and strongest in L. l. mexicanus and L. l. excubitorides. Although believed to be nonmigratory, long-distance movements of individuals were observed in L. ludovicianus and L. l. mexicanus. Our data support a pattern of chain migration, again most notable in the western half of the species nonbreeding range, and differential migration based on age.

Main conclusions: Our study provides of one such of the first quantitative measures of migratory connectivity and is among the first studies of a short-distance migratory passerine in North America. The higher migratory connectivity among western, versus eastern populations, and less severe population declines attributable to habitat loss or reproductive success, may result in more localized and/or less severe limiting factors for western populations and more severe on the Atlantic coast and Mississippi Alluvial Valley wintering grounds.}, } @article {pmid30519395, year = {2018}, author = {Hautier, Y and Vojtech, E and Hector, A}, title = {The importance of competition for light depends on productivity and disturbance.}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10655-10661}, pmid = {30519395}, issn = {2045-7758}, abstract = {Eutrophication is a major cause of biodiversity loss. In grasslands, this appears to occur due to asymmetric competition for light following the increases in aboveground biomass production. Here, we report the results of an experiment with five grass species that tests how well-competitive outcomes can be predicted under a factorial combination of fertilized and disturbed (frequent cutting) conditions. Under fertile conditions, our results confirm earlier success in predicting short-term competitive outcomes based on light interception in monocultures. This effect was maintained but weakened under less fertile conditions with competition becoming more symmetric. However, under disturbed conditions, competitive outcomes could not be predicted from differences in light interception in monocultures regardless of fertility. Our results support the idea that competition in grasslands shifts from symmetric to asymmetric as fertility increases but that disturbance destroys this relationship, presumably by preventing the development of differences in canopy structure and reducing competition for light.}, } @article {pmid30519394, year = {2018}, author = {LaBonte, NR and Woeste, KE}, title = {Pooled whole-genome sequencing of interspecific chestnut (Castanea) hybrids reveals loci associated with differences in caching behavior of fox squirrels (Sciurus niger L.).}, journal = {Ecology and evolution}, volume = {8}, number = {22}, pages = {10638-10654}, pmid = {30519394}, issn = {2045-7758}, abstract = {Dispersal of seeds by scatter-hoarding rodents is common among tropical and temperate tree species, including chestnuts in the genus Castanea. Backcrossed (BC) interspecific hybrid chestnuts exhibit wide variation in seed traits: as the parent species (Castanea dentata and C. mollissima) have distinct seed phenotypes and tend to be handled differently by seed dispersers, phenotypic variation in BC trees is likely due to inheritance of genes that have undergone divergent evolution in the parent species. To identify candidate genomic regions for interspecific differences in seed dispersal, we used tagged seeds to measure average dispersal distance for seeds of third-generation BC chestnuts and sequenced pooled whole genomes of mother trees with contrasting seed dispersal: high caching rate/long distance; low caching rate/short distance; no caching. Candidate regions affecting seed dispersal were identified as loci with more C. mollissima alleles in the high caching rate/ long-distance pool than expected by chance and observed in the other two pools. Functional annotations of candidate regions included predicted lipid metabolism, dormancy regulation, seed development, and carbohydrate metabolism genes. The results support the hypothesis that perception of seed dormancy is a predominant factor in squirrel caching decisions, and also indicate profitable directions for future work on the evolutionary genomics of trees and coevolved seed dispersers.}, } @article {pmid30519380, year = {2018}, author = {Jang, H and Woo, J and Lee, Y and Negrete, F and Finkelstein, S and Chase, HR and Addy, N and Ewing, L and Beaubrun, JJG and Patel, I and Gangiredla, J and Eshwar, A and Jaradat, ZW and Seo, K and Shabarinath, S and Fanning, S and Stephan, R and Lehner, A and Tall, BD and Gopinath, GR}, title = {Draft genomes of Cronobacter sakazakii strains isolated from dried spices bring unique insights into the diversity of plant-associated strains.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {35}, pmid = {30519380}, issn = {1944-3277}, abstract = {Cronobacter sakazakii is a Gram-negative opportunistic pathogen that causes life- threatening infantile infections, such as meningitis, septicemia, and necrotizing enterocolitis, as well as pneumonia, septicemia, and urinary tract and wound infections in adults. Here, we report 26 draft genome sequences of C. sakazakii, which were obtained from dried spices from the USA, the Middle East, China, and the Republic of Korea. The average genome size of the C. sakazakii genomes was 4393 kb, with an average of 4055 protein coding genes, and an average genome G + C content of 56.9%. The genomes contained genes related to carbohydrate transport and metabolism, amino acid transport and metabolism, and cell wall/membrane biogenesis. In addition, we identified genes encoding proteins involved in osmotic responses such as DnaJ, Aquaproin Z, ProQ, and TreF, as well as virulence-related and heat shock-related proteins. Interestingly, a metabolic island comprised of a variably-sized xylose utilization operon was found within the spice-associated C. sakazakii genomes, which supports the hypothesis that plants may serve as transmission vectors or alternative hosts for Cronobacter species. The presence of the genes identified in this study can support the remarkable phenotypic traits of C. sakazakii such as the organism's capabilities of adaptation and survival in response to adverse growth environmental conditions (e.g. osmotic and desiccative stresses). Accordingly, the genome analyses provided insights into many aspects of physiology and evolutionary history of this important foodborne pathogen.}, } @article {pmid30518906, year = {2018}, author = {}, title = {Black-hole bounty, Ebola emergency and UK science minister resigns.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {10-11}, doi = {10.1038/d41586-018-07590-9}, pmid = {30518906}, issn = {1476-4687}, } @article {pmid30518905, year = {2018}, author = {Fischer, S}, title = {A beginner's guide to space travel and seafood.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {154}, doi = {10.1038/d41586-018-07615-3}, pmid = {30518905}, issn = {1476-4687}, } @article {pmid30518904, year = {2018}, author = {Graber-Stiehl, I}, title = {The silent epidemic killing more people than HIV, malaria or TB.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {24-26}, doi = {10.1038/d41586-018-07592-7}, pmid = {30518904}, issn = {1476-4687}, } @article {pmid30518903, year = {2018}, author = {Figueres, C and Le Quéré, C and Mahindra, A and Bäte, O and Whiteman, G and Peters, G and Guan, D}, title = {Emissions are still rising: ramp up the cuts.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {27-30}, doi = {10.1038/d41586-018-07585-6}, pmid = {30518903}, issn = {1476-4687}, } @article {pmid30518902, year = {2018}, author = {Xu, Y and Ramanathan, V and Victor, DG}, title = {Global warming will happen faster than we think.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {30-32}, doi = {10.1038/d41586-018-07586-5}, pmid = {30518902}, issn = {1476-4687}, } @article {pmid30518901, year = {2018}, author = {}, title = {Rules for a safe climate.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-018-07633-1}, pmid = {30518901}, issn = {1476-4687}, } @article {pmid30518900, year = {2018}, author = {Savage, N}, title = {Computer logic meets cell biology: how cell science is getting an upgrade.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {S1-S3}, doi = {10.1038/d41586-018-07595-4}, pmid = {30518900}, issn = {1476-4687}, } @article {pmid30518899, year = {2018}, author = {Schuitema, G and Steg, L}, title = {Road charges in real time are not a silver bullet.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {39}, doi = {10.1038/d41586-018-07612-6}, pmid = {30518899}, issn = {1476-4687}, } @article {pmid30518898, year = {2018}, author = {Jennions, M and Lanfear, R and Nakagawa, S}, title = {Plan S will hit some academic societies hard.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {39}, doi = {10.1038/d41586-018-07609-1}, pmid = {30518898}, issn = {1476-4687}, } @article {pmid30518897, year = {2018}, author = {Venâncio, MD and Pope, K and Sieber, S}, title = {Brazil's new government threatens food security and biodiversity.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {39}, doi = {10.1038/d41586-018-07611-7}, pmid = {30518897}, issn = {1476-4687}, } @article {pmid30518896, year = {2018}, author = {Basile, S and Lerner, M and Rostamnezhad, K}, title = {Boost university voices at COP24 UN climate meeting.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {39}, doi = {10.1038/d41586-018-07610-8}, pmid = {30518896}, issn = {1476-4687}, } @article {pmid30518895, year = {2018}, author = {Khan, SA}, title = {Helmholtz mentored many Nobelists.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {39}, doi = {10.1038/d41586-018-07613-5}, pmid = {30518895}, issn = {1476-4687}, } @article {pmid30518894, year = {2018}, author = {Woo, S}, title = {Elusive spin textures discovered.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {43-44}, doi = {10.1038/d41586-018-07561-0}, pmid = {30518894}, issn = {1476-4687}, } @article {pmid30518893, year = {2018}, author = {Sutton, MA and Howard, CM}, title = {Satellite pinpoints ammonia sources globally.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {49-50}, doi = {10.1038/d41586-018-07584-7}, pmid = {30518893}, issn = {1476-4687}, } @article {pmid30518891, year = {2018}, author = {Berger, JB and Wadley, HNG and McMeeking, RM}, title = {Berger et al. reply.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {E2-E4}, doi = {10.1038/s41586-018-0725-7}, pmid = {30518891}, issn = {1476-4687}, } @article {pmid30518890, year = {2018}, author = {, }, title = {An experiment to search for dark-matter interactions using sodium iodide detectors.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {83-86}, doi = {10.1038/s41586-018-0739-1}, pmid = {30518890}, issn = {1476-4687}, support = {DE-FC52-08NA28752//Department of Energy/International ; }, abstract = {Observations of galaxies and primordial radiation suggest that the Universe is made mostly of non-luminous dark matter1,2. Several new types of fundamental particle have been proposed as candidates for dark matter3, such as weakly interacting massive particles (WIMPs)4,5. These particles would be expected to interact with nuclei in suitable detector materials on Earth, for example, causing them to recoil. However, no definitive signal from such dark-matter interactions has been detected despite concerted efforts by many collaborations6. One exception is the much-debated claim by the DAMA collaboration of a statistically significant (more than nine standard deviations) annual modulation in the rate of nuclear interaction events. Annual modulation is expected because of the variation in Earth's velocity relative to the Galaxy's dark-matter halo that arises from Earth's orbital motion around the Sun. DAMA observed a modulation in the rate of interaction events in their detector7-9 with a period and phase consistent with that expected for WIMPs10-12. Several groups have been working to develop experiments with the aim of reproducing DAMA's results using the same target medium (sodium iodide)13-17. To determine whether there is evidence for an excess of events above the expected background in sodium iodide and to look for evidence of an annual modulation, the COSINE-100 experiment uses sodium iodide as the target medium to carry out a model-independent test of DAMA's claim. Here we report results from the initial operation of the COSINE-100 experiment related to the first task18,19. We observe no excess of signal-like events above the expected background in the first 59.5 days of data from COSINE-100. Assuming the so-called standard dark-matter halo model, this result rules out WIMP-nucleon interactions as the cause of the annual modulation observed by the DAMA collaboration20-23. The exclusion limit on the WIMP-sodium interaction cross-section is 1.14 × 10-40 cm2 for 10-GeV c-2 WIMPs at a 90% confidence level. The COSINE-100 experiment will continue to collect data for two more years, enabling a model-independent test of the annual modulation observed by the DAMA collaboration.}, } @article {pmid30518889, year = {2018}, author = {Yu, XZ and Koshibae, W and Tokunaga, Y and Shibata, K and Taguchi, Y and Nagaosa, N and Tokura, Y}, title = {Transformation between meron and skyrmion topological spin textures in a chiral magnet.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {95-98}, doi = {10.1038/s41586-018-0745-3}, pmid = {30518889}, issn = {1476-4687}, abstract = {Crystal lattices with tetragonal or hexagonal structure often exhibit structural transitions in response to external stimuli1. Similar behaviour is anticipated for the lattice forms of topological spin textures, such as lattices composed of merons and antimerons or skyrmions and antiskyrmions (types of vortex related to the distribution of electron spins in a magnetic field), but has yet to be verified experimentally2,3. Here we report real-space observations of spin textures in a thin plate of the chiral-lattice magnet Co8Zn9Mn3, which exhibits in-plane magnetic anisotropy. The observations demonstrate the emergence of a two-dimensional square lattice of merons and antimerons from a helical state, and its transformation into a hexagonal lattice of skyrmions in the presence of a magnetic field at room temperature. Sequential observations with decreasing temperature reveal that the topologically protected skyrmions remain robust to changes in temperature, whereas the square lattice of merons and antimerons relaxes to non-topological in-plane spin helices, highlighting the different topological stabilities of merons, antimerons and skyrmions. Our results demonstrate the rich variety of topological spin textures and their lattice forms, and should stimulate further investigation of emergent electromagnetic properties.}, } @article {pmid30518888, year = {2018}, author = {Van Damme, M and Clarisse, L and Whitburn, S and Hadji-Lazaro, J and Hurtmans, D and Clerbaux, C and Coheur, PF}, title = {Industrial and agricultural ammonia point sources exposed.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {99-103}, doi = {10.1038/s41586-018-0747-1}, pmid = {30518888}, issn = {1476-4687}, abstract = {Through its important role in the formation of particulate matter, atmospheric ammonia affects air quality and has implications for human health and life expectancy1,2. Excess ammonia in the environment also contributes to the acidification and eutrophication of ecosystems3-5 and to climate change6. Anthropogenic emissions dominate natural ones and mostly originate from agricultural, domestic and industrial activities7. However, the total ammonia budget and the attribution of emissions to specific sources remain highly uncertain across different spatial scales7-9. Here we identify, categorize and quantify the world's ammonia emission hotspots using a high-resolution map of atmospheric ammonia obtained from almost a decade of daily IASI satellite observations. We report 248 hotspots with diameters smaller than 50 kilometres, which we associate with either a single point source or a cluster of agricultural and industrial point sources-with the exception of one hotspot, which can be traced back to a natural source. The state-of-the-art EDGAR emission inventory10 mostly agrees with satellite-derived emission fluxes within a factor of three for larger regions. However, it does not adequately represent the majority of point sources that we identified and underestimates the emissions of two-thirds of them by at least one order of magnitude. Industrial emitters in particular are often found to be displaced or missing. Our results suggest that it is necessary to completely revisit the emission inventories of anthropogenic ammonia sources and to account for the rapid evolution of such sources over time. This will lead to better health and environmental impact assessments of atmospheric ammonia and the implementation of suitable nitrogen management strategies.}, } @article {pmid30518887, year = {2018}, author = {Trusel, LD and Das, SB and Osman, MB and Evans, MJ and Smith, BE and Fettweis, X and McConnell, JR and Noël, BPY and van den Broeke, MR}, title = {Nonlinear rise in Greenland runoff in response to post-industrial Arctic warming.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {104-108}, doi = {10.1038/s41586-018-0752-4}, pmid = {30518887}, issn = {1476-4687}, support = {OPP-1205196//National Science Foundation/International ; PLR-1418256//National Science Foundation/International ; ARC-1205062//National Science Foundation/International ; OPP-1205008//National Science Foundation/International ; }, abstract = {The Greenland ice sheet (GrIS) is a growing contributor to global sea-level rise1, with recent ice mass loss dominated by surface meltwater runoff2,3. Satellite observations reveal positive trends in GrIS surface melt extent4, but melt variability, intensity and runoff remain uncertain before the satellite era. Here we present the first continuous, multi-century and observationally constrained record of GrIS surface melt intensity and runoff, revealing that the magnitude of recent GrIS melting is exceptional over at least the last 350 years. We develop this record through stratigraphic analysis of central west Greenland ice cores, and demonstrate that measurements of refrozen melt layers in percolation zone ice cores can be used to quantifiably, and reproducibly, reconstruct past melt rates. We show significant (P < 0.01) and spatially extensive correlations between these ice-core-derived melt records and modelled melt rates5,6 and satellite-derived melt duration4 across Greenland more broadly, enabling the reconstruction of past ice-sheet-scale surface melt intensity and runoff. We find that the initiation of increases in GrIS melting closely follow the onset of industrial-era Arctic warming in the mid-1800s, but that the magnitude of GrIS melting has only recently emerged beyond the range of natural variability. Owing to a nonlinear response of surface melting to increasing summer air temperatures, continued atmospheric warming will lead to rapid increases in GrIS runoff and sea-level contributions.}, } @article {pmid30518886, year = {2018}, author = {Milton, GW}, title = {Stiff competition.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {E1}, doi = {10.1038/s41586-018-0724-8}, pmid = {30518886}, issn = {1476-4687}, } @article {pmid30518864, year = {2019}, author = {Higuchi, S and Sugahara, F and Pascual-Anaya, J and Takagi, W and Oisi, Y and Kuratani, S}, title = {Inner ear development in cyclostomes and evolution of the vertebrate semicircular canals.}, journal = {Nature}, volume = {565}, number = {7739}, pages = {347-350}, doi = {10.1038/s41586-018-0782-y}, pmid = {30518864}, issn = {1476-4687}, abstract = {Jawed vertebrates have inner ears with three semicircular canals, the presence of which has been used as a key to understanding evolutionary relationships. Ostracoderms, the jawless stem gnathostomes, had only two canals and lacked the lateral canal1-3. Lampreys, which are modern cyclostomes, are generally thought to possess two semicircular canals whereas the hagfishes-which are also cyclostomes-have only a single canal, which used to be regarded as a more primitive trait1,4. However, recent molecular and developmental analyses have strongly supported the monophyly of cyclostomes5-7, which has left the evolutionary trajectory of the vertebrate inner ear unclear8. Here we show the differentiation of the otic vesicle of the lamprey Lethenteron camtschaticum and inshore hagfish Eptatretus burgeri. This is the first time, to our knowledge, that the development of the hagfish inner ear is reported. We found that canal development in the lamprey starts with two depressions-which is reminiscent of the early developmental pattern of the inner ear in modern gnathostomes. These cyclostome otic vesicles show a pattern of expression of regulatory genes, including OTX genes, that is comparable to that of gnathosomes. Although two depressions appear in the lamprey vesicle, they subsequently fuse to form a single canal that is similar to that of hagfishes. Complete separation of the depressions results in anterior and posterior canals in gnathostomes. The single depression of the vesicle in hagfishes thus appears to be a secondarily derived trait. Furthermore, the lateral canal in crown gnathostomes was acquired secondarily-not by de novo acquisition of an OTX expression domain, but by the evolution of a developmental program downstream of the OTX genes.}, } @article {pmid30518863, year = {2018}, author = {Längin, M and Mayr, T and Reichart, B and Michel, S and Buchholz, S and Guethoff, S and Dashkevich, A and Baehr, A and Egerer, S and Bauer, A and Mihalj, M and Panelli, A and Issl, L and Ying, J and Fresch, AK and Buttgereit, I and Mokelke, M and Radan, J and Werner, F and Lutzmann, I and Steen, S and Sjöberg, T and Paskevicius, A and Qiuming, L and Sfriso, R and Rieben, R and Dahlhoff, M and Kessler, B and Kemter, E and Klett, K and Hinkel, R and Kupatt, C and Falkenau, A and Reu, S and Ellgass, R and Herzog, R and Binder, U and Wich, G and Skerra, A and Ayares, D and Kind, A and Schönmann, U and Kaup, FJ and Hagl, C and Wolf, E and Klymiuk, N and Brenner, P and Abicht, JM}, title = {Consistent success in life-supporting porcine cardiac xenotransplantation.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {430-433}, doi = {10.1038/s41586-018-0765-z}, pmid = {30518863}, issn = {1476-4687}, abstract = {Heart transplantation is the only cure for patients with terminal cardiac failure, but the supply of allogeneic donor organs falls far short of the clinical need1-3. Xenotransplantation of genetically modified pig hearts has been discussed as a potential alternative4. Genetically multi-modified pig hearts that lack galactose-α1,3-galactose epitopes (α1,3-galactosyltransferase knockout) and express a human membrane cofactor protein (CD46) and human thrombomodulin have survived for up to 945 days after heterotopic abdominal transplantation in baboons5. This model demonstrated long-term acceptance of discordant xenografts with safe immunosuppression but did not predict their life-supporting function. Despite 25 years of extensive research, the maximum survival of a baboon after heart replacement with a porcine xenograft was only 57 days and this was achieved, to our knowledge, only once6. Here we show that α1,3-galactosyltransferase-knockout pig hearts that express human CD46 and thrombomodulin require non-ischaemic preservation with continuous perfusion and control of post-transplantation growth to ensure long-term orthotopic function of the xenograft in baboons, the most stringent preclinical xenotransplantation model. Consistent life-supporting function of xenografted hearts for up to 195 days is a milestone on the way to clinical cardiac xenotransplantation7.}, } @article {pmid30518862, year = {2018}, author = {Lindgren, J and Sjövall, P and Thiel, V and Zheng, W and Ito, S and Wakamatsu, K and Hauff, R and Kear, BP and Engdahl, A and Alwmark, C and Eriksson, ME and Jarenmark, M and Sachs, S and Ahlberg, PE and Marone, F and Kuriyama, T and Gustafsson, O and Malmberg, P and Thomen, A and Rodríguez-Meizoso, I and Uvdal, P and Ojika, M and Schweitzer, MH}, title = {Soft-tissue evidence for homeothermy and crypsis in a Jurassic ichthyosaur.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {359-365}, doi = {10.1038/s41586-018-0775-x}, pmid = {30518862}, issn = {1476-4687}, support = {ECCS-1542015//National Science Foundation/International ; }, abstract = {Ichthyosaurs are extinct marine reptiles that display a notable external similarity to modern toothed whales. Here we show that this resemblance is more than skin deep. We apply a multidisciplinary experimental approach to characterize the cellular and molecular composition of integumental tissues in an exceptionally preserved specimen of the Early Jurassic ichthyosaur Stenopterygius. Our analyses recovered still-flexible remnants of the original scaleless skin, which comprises morphologically distinct epidermal and dermal layers. These are underlain by insulating blubber that would have augmented streamlining, buoyancy and homeothermy. Additionally, we identify endogenous proteinaceous and lipid constituents, together with keratinocytes and branched melanophores that contain eumelanin pigment. Distributional variation of melanophores across the body suggests countershading, possibly enhanced by physiological adjustments of colour to enable photoprotection, concealment and/or thermoregulation. Convergence of ichthyosaurs with extant marine amniotes thus extends to the ultrastructural and molecular levels, reflecting the omnipresent constraints of their shared adaptation to pelagic life.}, } @article {pmid30518861, year = {2018}, author = {Schmied, WH and Tnimov, Z and Uttamapinant, C and Rae, CD and Fried, SD and Chin, JW}, title = {Controlling orthogonal ribosome subunit interactions enables evolution of new function.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {444-448}, doi = {10.1038/s41586-018-0773-z}, pmid = {30518861}, issn = {1476-4687}, support = {MC-U105184332//Wellcome Trust/United Kingdom ; }, abstract = {Orthogonal ribosomes are unnatural ribosomes that are directed towards orthogonal messenger RNAs in Escherichia coli, through an altered version of the 16S ribosomal RNA of the small subunit1. Directed evolution of orthogonal ribosomes has provided access to new ribosomal function, and the evolved orthogonal ribosomes have enabled the encoding of multiple non-canonical amino acids into proteins2-4. The original orthogonal ribosomes shared the pool of 23S ribosomal RNAs, contained in the large subunit, with endogenous ribosomes. Selectively directing a new 23S rRNA to an orthogonal mRNA, by controlling the association between the orthogonal 16S rRNAs and 23S rRNAs, would enable the evolution of new function in the large subunit. Previous work covalently linked orthogonal 16S rRNA and a circularly permuted 23S rRNA to create orthogonal ribosomes with low activity5,6; however, the linked subunits in these ribosomes do not associate specifically with each other, and mediate translation by associating with endogenous subunits. Here we discover engineered orthogonal 'stapled' ribosomes (with subunits linked through an optimized RNA staple) with activities comparable to that of the parent orthogonal ribosome; they minimize association with endogenous subunits and mediate translation of orthogonal mRNAs through the association of stapled subunits. We evolve cells with genomically encoded stapled ribosomes as the sole ribosomes, which support cellular growth at similar rates to natural ribosomes. Moreover, we visualize the engineered stapled ribosome structure by cryo-electron microscopy at 3.0 Å, revealing how the staple links the subunits and controls their association. We demonstrate the utility of controlling subunit association by evolving orthogonal stapled ribosomes which efficiently polymerize a sequence of monomers that the natural ribosome is intrinsically unable to translate. Our work provides a foundation for evolving the rRNA of the entire orthogonal ribosome for the encoded cellular synthesis of non-canonical biological polymers7.}, } @article {pmid30518860, year = {2018}, author = {Rosental, B and Kowarsky, M and Seita, J and Corey, DM and Ishizuka, KJ and Palmeri, KJ and Chen, SY and Sinha, R and Okamoto, J and Mantalas, G and Manni, L and Raveh, T and Clarke, DN and Tsai, JM and Newman, AM and Neff, NF and Nolan, GP and Quake, SR and Weissman, IL and Voskoboynik, A}, title = {Complex mammalian-like haematopoietic system found in a colonial chordate.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {425-429}, doi = {10.1038/s41586-018-0783-x}, pmid = {30518860}, issn = {1476-4687}, support = {T32 AI007290/AI/NIAID NIH HHS/United States ; R01 AG037968/AG/NIA NIH HHS/United States ; T32HL120824-03/HL/NHLBI NIH HHS/United States ; R01 GM100315/GM/NIGMS NIH HHS/United States ; R56 AI089968/AI/NIAID NIH HHS/United States ; T32 HL120824/HL/NHLBI NIH HHS/United States ; 5T32AI07290-28/AI/NIAID NIH HHS/United States ; }, abstract = {Haematopoiesis is an essential process that evolved in multicellular animals. At the heart of this process are haematopoietic stem cells (HSCs), which are multipotent and self-renewing, and generate the entire repertoire of blood and immune cells throughout an animal's life1. Although there have been comprehensive studies on self-renewal, differentiation, physiological regulation and niche occupation in vertebrate HSCs, relatively little is known about the evolutionary origin and niches of these cells. Here we describe the haematopoietic system of Botryllus schlosseri, a colonial tunicate that has a vasculature and circulating blood cells, and interesting stem-cell biology and immunity characteristics2-8. Self-recognition between genetically compatible B. schlosseri colonies leads to the formation of natural parabionts with shared circulation, whereas incompatible colonies reject each other3,4,7. Using flow cytometry, whole-transcriptome sequencing of defined cell populations and diverse functional assays, we identify HSCs, progenitors, immune effector cells and an HSC niche, and demonstrate that self-recognition inhibits allospecific cytotoxic reactions. Our results show that HSC and myeloid lineage immune cells emerged in a common ancestor of tunicates and vertebrates, and also suggest that haematopoietic bone marrow and the B. schlosseri endostyle niche evolved from a common origin.}, } @article {pmid30518859, year = {2018}, author = {Leroy, F and Park, J and Asok, A and Brann, DH and Meira, T and Boyle, LM and Buss, EW and Kandel, ER and Siegelbaum, SA}, title = {A circuit from hippocampal CA2 to lateral septum disinhibits social aggression.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {213-218}, doi = {10.1038/s41586-018-0772-0}, pmid = {30518859}, issn = {1476-4687}, support = {F32 MH114306/MH/NIMH NIH HHS/United States ; R01 MH104602/MH/NIMH NIH HHS/United States ; R01 MH106629/MH/NIMH NIH HHS/United States ; }, abstract = {Although the hippocampus is known to be important for declarative memory, it is less clear how hippocampal output regulates motivated behaviours, such as social aggression. Here we report that pyramidal neurons in the CA2 region of the hippocampus, which are important for social memory, promote social aggression in mice. This action depends on output from CA2 to the lateral septum, which is selectively enhanced immediately before an attack. Activation of the lateral septum by CA2 recruits a circuit that disinhibits a subnucleus of the ventromedial hypothalamus that is known to trigger attack. The social hormone arginine vasopressin enhances social aggression by acting on arginine vasopressin 1b receptors on CA2 presynaptic terminals in the lateral septum to facilitate excitatory synaptic transmission. In this manner, release of arginine vasopressin in the lateral septum, driven by an animal's internal state, may serve as a modulatory control that determines whether CA2 activity leads to declarative memory of a social encounter and/or promotes motivated social aggression.}, } @article {pmid30518858, year = {2019}, author = {Williams, CD and Mukhopadhyay, S}, title = {Capture of nebular gases during Earth's accretion is preserved in deep-mantle neon.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {78-81}, doi = {10.1038/s41586-018-0771-1}, pmid = {30518858}, issn = {1476-4687}, support = {EAR-1250419//National Science Foundation/International ; }, abstract = {Evidence for the capture of nebular gases by planetary interiors would place important constraints on models of planet formation. These constraints include accretion timescales, thermal evolution, volatile compositions and planetary redox states1-7. Retention of nebular gases by planetary interiors also constrains the dynamics of outgassing and volatile loss associated with the assembly and ensuing evolution of terrestrial planets. But evidence for such gases in Earth's interior remains controversial8-14. The ratio of the two primordial neon isotopes, 20Ne/22Ne, is significantly different for the three potential sources of Earth's volatiles: nebular gas15, solar-wind-irradiated material16 and CI chondrites17. Therefore, the 20Ne/22Ne ratio is a powerful tool for assessing the source of volatiles in Earth's interior. Here we present neon isotope measurements from deep mantle plumes that reveal 20Ne/22Ne ratios of up to 13.03 ± 0.04 (2 standard deviations). These ratios are demonstrably higher than those for solar-wind-irradiated material and CI chondrites, requiring the presence of nebular neon in the deep mantle. Furthermore, we determine a 20Ne/22Ne ratio for the primordial plume mantle of 13.23 ± 0.22 (2 standard deviations), which is indistinguishable from the nebular ratio, providing robust evidence for a reservoir of nebular gas preserved in the deep mantle today. The acquisition of nebular gases requires planetary embryos to grow to sufficiently large mass before the dissipation of the protoplanetary disk. Our observations also indicate distinct 20Ne/22Ne ratios between deep mantle plumes and mid-ocean-ridge basalts, which is best explained by addition of a chondritic component to the shallower mantle during the main phase of Earth's accretion and by subsequent recycling of seawater-derived neon in plate tectonic processes.}, } @article {pmid30518857, year = {2018}, author = {Biddy, BA and Kong, W and Kamimoto, K and Guo, C and Waye, SE and Sun, T and Morris, SA}, title = {Single-cell mapping of lineage and identity in direct reprogramming.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {219-224}, doi = {10.1038/s41586-018-0744-4}, pmid = {30518857}, issn = {1476-4687}, support = {R01 GM126112/GM/NIGMS NIH HHS/United States ; R21 HG009750/HG/NHGRI NIH HHS/United States ; P30-DK052574/DK/NIDDK NIH HHS/United States ; T32HG000045-18/HG/NHGRI NIH HHS/United States ; 5T32GM007200-42/GM/NIGMS NIH HHS/United States ; 5T32GM007067-44/GM/NIGMS NIH HHS/United States ; }, abstract = {Direct lineage reprogramming involves the conversion of cellular identity. Single-cell technologies are useful for deconstructing the considerable heterogeneity that emerges during lineage conversion. However, lineage relationships are typically lost during cell processing, complicating trajectory reconstruction. Here we present 'CellTagging', a combinatorial cell-indexing methodology that enables parallel capture of clonal history and cell identity, in which sequential rounds of cell labelling enable the construction of multi-level lineage trees. CellTagging and longitudinal tracking of fibroblast to induced endoderm progenitor reprogramming reveals two distinct trajectories: one leading to successfully reprogrammed cells, and one leading to a 'dead-end' state, paths determined in the earliest stages of lineage conversion. We find that expression of a putative methyltransferase, Mettl7a1, is associated with the successful reprogramming trajectory; adding Mettl7a1 to the reprogramming cocktail increases the yield of induced endoderm progenitors. Together, these results demonstrate the utility of our lineage-tracing method for revealing the dynamics of direct reprogramming.}, } @article {pmid30518856, year = {2018}, author = {Yu, Y and Pham, N and Xia, B and Papusha, A and Wang, G and Yan, Z and Peng, G and Chen, K and Ira, G}, title = {Dna2 nuclease deficiency results in large and complex DNA insertions at chromosomal breaks.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {287-290}, doi = {10.1038/s41586-018-0769-8}, pmid = {30518856}, issn = {1476-4687}, support = {R01 GM080600/GM/NIGMS NIH HHS/United States ; R01 GM125650/GM/NIGMS NIH HHS/United States ; R01 GM125632/GM/NIGMS NIH HHS/United States ; HL133254/HL/NHLBI NIH HHS/United States ; }, abstract = {Insertions of mobile elements1-4, mitochondrial DNA5 and fragments of nuclear chromosomes6 at DNA double-strand breaks (DSBs) threaten genome integrity and are common in cancer7-9. Insertions of chromosome fragments at V(D)J recombination loci can stimulate antibody diversification10. The origin of insertions of chromosomal fragments and the mechanisms that prevent such insertions remain unknown. Here we reveal a yeast mutant, lacking evolutionarily conserved Dna2 nuclease, that shows frequent insertions of sequences between approximately 0.1 and 1.5 kb in length into DSBs, with many insertions involving multiple joined DNA fragments. Sequencing of around 500 DNA inserts reveals that they originate from Ty retrotransposons (8%), ribosomal DNA (rDNA) (15%) and from throughout the genome, with preference for fragile regions such as origins of replication, R-loops, centromeres, telomeres or replication fork barriers. Inserted fragments are not lost from their original loci and therefore represent duplications. These duplications depend on nonhomologous end-joining (NHEJ) and Pol4. We propose a model in which alternative processing of DNA structures arising in Dna2-deficient cells can result in the release of DNA fragments and their capture at DSBs. Similar DNA insertions at DSBs are expected to occur in any cells with linear extrachromosomal DNA fragments.}, } @article {pmid30518855, year = {2018}, author = {Kronheim, S and Daniel-Ivad, M and Duan, Z and Hwang, S and Wong, AI and Mantel, I and Nodwell, JR and Maxwell, KL}, title = {A chemical defence against phage infection.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {283-286}, doi = {10.1038/s41586-018-0767-x}, pmid = {30518855}, issn = {1476-4687}, abstract = {The arms race between bacteria and the phages that infect them drives the continual evolution of diverse anti-phage defences. Previously described anti-phage systems have highly varied defence mechanisms1-11; however, all mechanisms rely on protein components to mediate defence. Here we report a chemical anti-phage defence system that is widespread in Streptomyces. We show that three naturally produced molecules that insert into DNA are able to block phage replication, whereas molecules that target DNA by other mechanisms do not. Because double-stranded DNA phages are the most numerous group in the biosphere and the production of secondary metabolites by bacteria is ubiquitous12, this mechanism of anti-phage defence probably has a major evolutionary role in shaping bacterial communities.}, } @article {pmid30518814, year = {2018}, author = {Simmonds, P and Aiewsakun, P and Katzourakis, A}, title = {Prisoners of war - host adaptation and its constraints on virus evolution.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0120-2}, pmid = {30518814}, issn = {1740-1534}, abstract = {Recent discoveries of contemporary genotypes of hepatitis B virus and parvovirus B19 in ancient human remains demonstrate that little genetic change has occurred in these viruses over 4,500-6,000 years. Endogenous viral elements in host genomes provide separate evidence that viruses similar to many major contemporary groups circulated 100 million years ago or earlier. In this Opinion article, we argue that the extraordinary conservation of virus genome sequences is best explained by a niche-filling model in which fitness optimization is rapidly achieved in their specific hosts. Whereas short-term substitution rates reflect the accumulation of tolerated sequence changes within adapted genomes, longer-term rates increasingly resemble those of their hosts as the evolving niche moulds and effectively imprisons the virus in co-adapted virus-host relationships. Contrastingly, viruses that jump hosts undergo strong and stringent adaptive selection as they maximize their fit to their new niche. This adaptive capability may paradoxically create evolutionary stasis in long-term host relationships. While viruses can evolve and adapt rapidly, their hosts may ultimately shape their longer-term evolution.}, } @article {pmid30518564, year = {2018}, author = {Lake, EW and Muretta, JM and Thompson, AR and Rasmussen, DM and Majumdar, A and Faber, EB and Ruff, EF and Thomas, DD and Levinson, NM}, title = {Quantitative conformational profiling of kinase inhibitors reveals origins of selectivity for Aurora kinase activation states.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11894-E11903}, doi = {10.1073/pnas.1811158115}, pmid = {30518564}, issn = {1091-6490}, support = {R21 CA217695/CA/NCI NIH HHS/United States ; T32 GM008244/GM/NIGMS NIH HHS/United States ; }, abstract = {Protein kinases undergo large-scale structural changes that tightly regulate function and control recognition by small-molecule inhibitors. Methods for quantifying the conformational effects of inhibitors and linking them to an understanding of selectivity patterns have long been elusive. We have developed an ultrafast time-resolved fluorescence methodology that tracks structural movements of the kinase activation loop in solution with angstrom-level precision, and can resolve multiple structural states and quantify conformational shifts between states. Profiling a panel of clinically relevant Aurora kinase inhibitors against the mitotic kinase Aurora A revealed a wide range of conformational preferences, with all inhibitors promoting either the active DFG-in state or the inactive DFG-out state, but to widely differing extents. Remarkably, these conformational preferences explain broad patterns of inhibitor selectivity across different activation states of Aurora A, with DFG-out inhibitors preferentially binding Aurora A activated by phosphorylation on the activation loop, which dynamically samples the DFG-out state, and DFG-in inhibitors binding preferentially to Aurora A constrained in the DFG-in state by its allosteric activator Tpx2. The results suggest that many inhibitors currently in clinical development may be capable of differentiating between Aurora A signaling pathways implicated in normal mitotic control and in melanoma, neuroblastoma, and prostate cancer. The technology is applicable to a wide range of clinically important kinases and could provide a wealth of valuable structure-activity information for the development of inhibitors that exploit differences in conformational dynamics to achieve enhanced selectivity.}, } @article {pmid30518563, year = {2018}, author = {Zeng, Z and Liu, XL and Wei, JH and Summons, RE and Welander, PV}, title = {Calditol-linked membrane lipids are required for acid tolerance in Sulfolobus acidocaldarius.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12932-12937}, doi = {10.1073/pnas.1814048115}, pmid = {30518563}, issn = {1091-6490}, abstract = {Archaea have many unique physiological features of which the lipid composition of their cellular membranes is the most striking. Archaeal ether-linked isoprenoidal membranes can occur as bilayers or monolayers, possess diverse polar head groups, and a multiplicity of ring structures in the isoprenoidal cores. These lipid structures are proposed to provide protection from the extreme temperature, pH, salinity, and nutrient-starved conditions that many archaea inhabit. However, many questions remain regarding the synthesis and physiological role of some of the more complex archaeal lipids. In this study, we identify a radical S-adenosylmethionine (SAM) protein in Sulfolobus acidocaldarius required for the synthesis of a unique cyclopentyl head group, known as calditol. Calditol-linked glycerol dibiphytanyl glycerol tetraethers (GDGTs) are membrane spanning lipids in which calditol is ether bonded to the glycerol backbone and whose production is restricted to a subset of thermoacidophilic archaea of the Sulfolobales order within the Crenarchaeota phylum. Several studies have focused on the enzymatic mechanism for the synthesis of the calditol moiety, but to date no protein that catalyzes this reaction has been discovered. Phylogenetic analyses of this putative calditol synthase (Cds) reveal the genetic potential for calditol-GDGT synthesis in phyla other than the Crenarchaeota, including the Korarchaeota and Marsarchaeota. In addition, we identify Cds homologs in metagenomes predominantly from acidic ecosystems. Finally, we demonstrate that deletion of calditol synthesis renders S. acidocaldarius sensitive to extremely low pH, indicating that calditol plays a critical role in protecting archaeal cells from acidic stress.}, } @article {pmid30518562, year = {2018}, author = {Gamal El-Din, TM and Lenaeus, MJ and Zheng, N and Catterall, WA}, title = {Fenestrations control resting-state block of a voltage-gated sodium channel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13111-13116}, doi = {10.1073/pnas.1814928115}, pmid = {30518562}, issn = {1091-6490}, support = {R01 HL112808/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Potency of drug action is usually determined by binding to a specific receptor site on target proteins. In contrast to this conventional paradigm, we show here that potency of local anesthetics (LAs) and antiarrhythmic drugs (AADs) that block sodium channels is controlled by fenestrations that allow drug access to the receptor site directly from the membrane phase. Voltage-gated sodium channels initiate action potentials in nerve and cardiac muscle, where their hyperactivity causes pain and cardiac arrhythmia, respectively. LAs and AADs selectively block sodium channels in rapidly firing nerve and muscle cells to relieve these conditions. The structure of the ancestral bacterial sodium channel NaVAb, which is also blocked by LAs and AADs, revealed fenestrations connecting the lipid phase of the membrane to the central cavity of the pore. We cocrystallized lidocaine and flecainide with NavAb, which revealed strong drug-dependent electron density in the central cavity of the pore. Mutation of the contact residue T206 greatly reduced drug potency, confirming this site as the receptor for LAs and AADs. Strikingly, mutations of the fenestration cap residue F203 changed fenestration size and had graded effects on resting-state block by flecainide, lidocaine, and benzocaine, the potencies of which were altered from 51- to 2.6-fold in order of their molecular size. These results show that conserved fenestrations in the pores of sodium channels are crucial pharmacologically and determine the level of resting-state block by widely used drugs. Fine-tuning drug access through fenestrations provides an unexpected avenue for structure-based design of ion-channel-blocking drugs.}, } @article {pmid30518561, year = {2018}, author = {Jeffery, C and Pagano, M and Hemingway, J and Valadez, JJ}, title = {Hybrid prevalence estimation: Method to improve intervention coverage estimations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13063-13068}, doi = {10.1073/pnas.1810287115}, pmid = {30518561}, issn = {1091-6490}, abstract = {Delivering excellent health services requires accurate health information systems (HIS) data. Poor-quality data can lead to poor judgments and outcomes. Unlike probability surveys, which are representative of the population and carry accuracy estimates, HIS do not, but in many countries the HIS is the primary source of data used for administrative estimates. However, HIS are not structured to detect gaps in service coverage and leave communities exposed to unnecessary health risks. Here we propose a method to improve informatics by combining HIS and probability survey data to construct a hybrid estimator. This technique provides a more accurate estimator than either data source alone and facilitates informed decision-making. We use data from vitamin A and polio vaccination campaigns in children from Madagascar and Benin to demonstrate the effect. The hybrid estimator is a weighted average of two measurements and produces SEs and 95% confidence intervals (CIs) for the hybrid and HIS estimators. The estimates of coverage proportions using the combined data and the survey estimates differ by no more than 3%, while decreasing the SE by 1-6%; the administrative estimates from the HIS and combined data estimates are very different, with 3-25 times larger CI, questioning the value of administrative estimates. Estimators of unknown accuracy may lead to poorly formulated policies and wasted resources. The hybrid estimator technique can be applied to disease prevention services for which population coverages are measured. This methodology creates more accurate estimators, alongside measured HIS errors, to improve tracking the public's health.}, } @article {pmid30518560, year = {2018}, author = {Doh, JK and White, JD and Zane, HK and Chang, YH and López, CS and Enns, CA and Beatty, KE}, title = {VIPER is a genetically encoded peptide tag for fluorescence and electron microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12961-12966}, doi = {10.1073/pnas.1808626115}, pmid = {30518560}, issn = {1091-6490}, support = {R01 GM122854/GM/NIGMS NIH HHS/United States ; }, abstract = {Many discoveries in cell biology rely on making specific proteins visible within their native cellular environment. There are various genetically encoded tags, such as fluorescent proteins, developed for fluorescence microscopy (FM). However, there are almost no genetically encoded tags that enable cellular proteins to be observed by both FM and electron microscopy (EM). Herein, we describe a technology for labeling proteins with diverse chemical reporters, including bright organic fluorophores for FM and electron-dense nanoparticles for EM. Our technology uses versatile interacting peptide (VIP) tags, a class of genetically encoded tag. We present VIPER, which consists of a coiled-coil heterodimer formed between the genetic tag, CoilE, and a probe-labeled peptide, CoilR. Using confocal FM, we demonstrate that VIPER can be used to highlight subcellular structures or to image receptor-mediated iron uptake. Additionally, we used VIPER to image the iron uptake machinery by correlative light and EM (CLEM). VIPER compared favorably with immunolabeling for imaging proteins by CLEM, and is an enabling technology for protein targets that cannot be immunolabeled. VIPER is a versatile peptide tag that can be used to label and track proteins with diverse chemical reporters observable by both FM and EM instrumentation.}, } @article {pmid30518559, year = {2019}, author = {Raut, R and Corbett, KS and Tennekoon, RN and Premawansa, S and Wijewickrama, A and Premawansa, G and Mieczkowski, P and Rückert, C and Ebel, GD and De Silva, AD and de Silva, AM}, title = {Dengue type 1 viruses circulating in humans are highly infectious and poorly neutralized by human antibodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {227-232}, doi = {10.1073/pnas.1812055115}, pmid = {30518559}, issn = {1091-6490}, support = {P01 AI106695/AI/NIAID NIH HHS/United States ; R01 AI107731/AI/NIAID NIH HHS/United States ; R25 GM055336/GM/NIGMS NIH HHS/United States ; T32 AI007419/AI/NIAID NIH HHS/United States ; }, abstract = {The four dengue virus (DENV) serotypes are mosquito-borne flaviviruses of humans. The interactions between DENVs and the human host that lead to asymptomatic, mild, or severe disease are poorly understood, in part, because laboratory models are poor surrogates for human DENV disease. Virologists are interested in how the properties of DENVs replicating in people compare with virions propagated on laboratory cell lines, which are widely used for research and vaccine development. Using clinical samples from a DENV type 1 epidemic in Sri Lanka and new ultrasensitive assays, we compared the properties of DENVs in human plasma and after one passage on laboratory cell lines. DENVs in plasma were 50- to 700-fold more infectious than cell culture-grown viruses. DENVs produced by laboratory cell lines were structurally immature and hypersensitive to neutralization by human antibodies compared with DENVs circulating in people. Human plasma and cell culture-derived virions had identical genome sequences, indicating that these phenotypic differences were due to the mature state of plasma virions. Several dengue vaccines are under development. Recent studies indicate that vaccine-induced antibodies that neutralized DENVs in cell culture assays were not sufficient for protecting people from DENV infections. Our results about structural differences between DENVs produced in humans versus cell lines may be key to understanding vaccine failure and developing better models for vaccine evaluation.}, } @article {pmid30518433, year = {2018}, author = {Aregay, W and Azale, T and Sisay, M and Gonete, KA}, title = {Utilization of long acting reversible contraceptive methods and associated factors among female college students in Gondar town, northwest Ethiopia, 2018: institutional based cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {862}, pmid = {30518433}, issn = {1756-0500}, abstract = {OBJECTIVES: Family planning is achieved through use of different contraceptive methods among which the most effective methods are modern family planning methods like long acting reversible contraceptive which includes intra-uterine contraceptive device and Implants. The objective of this primary study was to assess utilization of long acting reversible contraceptive methods among female college students in Gondar town, northwest Ethiopia.

RESULTS: The overall utilization of long acting reversible contraceptive methods among students was 20.4% (95% CI 18.1, 22.7) and the most commonly utilized long acting reversible contraceptive method was Implants 96.5% (95% CI 95.50, 97.50) followed by intra-uterine contraceptive device 3.5% (95% CI 2.97, 4.00). Marital status of the respondents [AOR = 3.97 (95% CI 2.05, 7.67)], discussion about long acting reversible contraceptive methods utilization with husbands or boyfriends [AOR = 2.20 (95% CI 1.19-4.06)] and attitude towards implants [AOR = 0.365 (95% CI 0.14, 0.93)] were found to be significantly associated with utilization of long acting reversible contraceptive among students.}, } @article {pmid30518420, year = {2018}, author = {Muturi, M and Bitek, A and Mwatondo, A and Osoro, E and Marwanga, D and Gura, Z and Ngere, P and Nganga, Z and Thumbi, SM and Njenga, K}, title = {Risk factors for human brucellosis among a pastoralist community in South-West Kenya, 2015.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {865}, pmid = {30518420}, issn = {1756-0500}, abstract = {OBJECTIVE: Brucellosis is one of the top five priority zoonosis in Kenya because of the socio-economic burden of the disease, especially among traditional, livestock keeping communities. We conducted a 1 year, hospital based, unmatched case-control study to determine risk factors for brucellosis among Maasai pastoralists of Kajiado County in 2016. A case was defined by a clinical criteria; fever or history of fever and two clinical signs suggestive of brucellosis and a positive competitive enzyme-linked immunosorbent assay test (c-ELISA). A control was defined as patients visiting the study facility with negative c-ELISA. Unconditional logistic regression was used to study association between exposure variables and brucellosis using odds ratios (OR) and 95% confidence intervals (CI).

RESULTS: Forty-three cases and 86 controls were recruited from a population of 4792 individuals in 801 households. The mean age for the cases was 48.7 years while that of the controls was 37.6 years. The dominant gender for both cases (62.7%) and controls (58.1%) groups was female. Regular consumption of un-boiled raw milk and assisting animals in delivery were significantly associated with brucellosis by OR 7.7 (95% CI 1.5-40.1) and OR 3.7 (95% CI 1.1-13.5), respectively.}, } @article {pmid30518415, year = {2018}, author = {Alonso, L and Creuzé-des-Châtelliers, C and Trabac, T and Dubost, A and Moënne-Loccoz, Y and Pommier, T}, title = {Rock substrate rather than black stain alterations drives microbial community structure in the passage of Lascaux Cave.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {216}, pmid = {30518415}, issn = {2049-2618}, abstract = {BACKGROUND: The World-famous UNESCO heritage from the Paleolithic human society, Lascaux Cave (France), has endeavored intense microclimatic perturbations, in part due to high touristic pressure. These perturbations have resulted in numerous disturbances of the cave ecosystem, including on its microbial compartment, which resulted in the formation of black stains especially on the rock faces of the passage. We investigated the cave microbiome in this part of Lascaux by sampling three mineral substrates (soil, banks, and inclined planes) on and outside stains to assess current cave microbial assemblage and explore the possibility that pigmented microorganisms involved in stain development occur as microbial consortia.

METHODS: Microbial abundance and diversity were assessed by means of quantitative PCR and high-throughput sequencing (Illumina MiSeq) of several DNA and cDNA taxonomic markers. Five sampling campaigns were carried out during winter and summer to embrace potential seasonal effect in this somewhat stable environment (based on measurements of temperature and CO2 concentration).

RESULTS: While the season or type of mineral substrate did not affect the abundances of bacteria and micro-eukaryotes on or outside stains, mineral substrate rather than stain presence appears to be the most significant factor determining microbial diversity and structuring microbial community, regardless of whether DNA or cDNA markers were considered. A phylogenetic signal was also detected in relation to substrate types, presence of stains but not with season among the OTUs common to the three substrates. Co-occurrence network analyses showed that most bacterial and fungal interactions were positive regardless of the factor tested (season, substrate, or stain), but these networks varied according to ecological conditions and time. Microorganisms known to harbor pigmentation ability were well established inside but also outside black stains, which may be prerequisite for subsequent stain formation.

CONCLUSIONS: This first high throughput sequencing performed in Lascaux Cave showed that black stains were secondary to mineral substrate in determining microbiome community structure, regardless of whether total or transcriptionally active bacterial and micro-eukaryotic communities were considered. These results revealed the potential for new stain formation and highlight the need for careful microbiome management to avoid further cave wall degradation.}, } @article {pmid30518414, year = {2018}, author = {Lopez-Garcia, LA and Demiray, L and Ruch-Marder, S and Hopp, AK and Hottiger, MO and Helbling, PM and Pavlou, MP}, title = {Validation of extracellular ligand-receptor interactions by Flow-TriCEPS.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {863}, pmid = {30518414}, issn = {1756-0500}, abstract = {OBJECTIVE: The advent of ligand-based receptor capture methodologies, allows the identification of unknown receptor candidates for orphan extracellular ligands. However, further target validation can be tedious, laborious and time-consuming. Here, we present a methodology that provides a fast and cost-efficient alternative for candidate target verification on living cells.

RESULTS: In the described methodology a ligand of interest (e.g. transferrin, epidermal growth factor or insulin) was conjugated to a linker (TriCEPS) that carries a biotin. To confirm ligand/receptor interactions, the ligand-TriCEPS conjugates were first added onto living cells and cells were subsequently labeled with a streptavidin-fluorophore and analyzed by flow cytometry (thus referred as Flow-TriCEPS). Flow-TriCEPS was also used to validate identified receptor candidates when combined with a siRNA knock down approach (i.e. reduction of expression levels). This approach is versatile as it can be applied for different classes of ligands (proteins, peptides, antibodies) and different cell lines. Moreover, the method is time-efficient since it takes advantage of the large variety of commercially available (and certified) siRNAs.}, } @article {pmid30518413, year = {2018}, author = {Hussack, G and Raphael, S and Lowden, MJ and Henry, KA}, title = {Isolation and characterization of camelid single-domain antibodies against HER2.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {866}, pmid = {30518413}, issn = {1756-0500}, abstract = {OBJECTIVE: To isolate and characterize novel high-affinity llama single-domain antibodies against human HER2.

RESULTS: We immunized a llama with human HER2, constructed a phage-displayed VHH library from the lymphocytes of the animal, and isolated six unique HER2-specific VHHs by panning. All six VHHs were unique at the amino acid level and were clonally unrelated, as reflected by their distinct CDR3 lengths. All six VHHs recognized recombinant human HER2 ectodomain with monovalent affinities ranging from 1 to 51 nM, had comparable affinities for cynomolgus monkey HER2, and bound HER2+ SKOV3 cells by flow cytometry. Three of the VHHs recognized recombinant murine HER2 with no loss of affinity compared with human and cynomolgus monkey HER2. The VHHs recognized three major epitopes on HER2 (including one conserved across the human, simian and murine orthologues), all of which were distinct from that of trastuzumab. These VHHs may be useful in the design of modular cancer immunotherapeutics.}, } @article {pmid30518404, year = {2018}, author = {Shaver, ZM and Bent, SS and Bilby, SR and Brown, M and Buser, A and Cuellar, IG and Davis, AJ and Doolan, L and Enriquez, FC and Estrada, A and Herner, S and Herron, JC and Hunn, AM and Hunter, M and Johnston, H and Koucky, O and Mackley, CC and Maghini, D and Mattoon, D and McDonald, HT and Sinks, H and Sprague, AJ and Sullivan, D and Tutar, A and Umphreys, A and Watson, C and Zweerink, D and Heyer, LJ and Poet, JL and Eckdahl, TT and Campbell, AM}, title = {Attempted use of PACE for riboswitch discovery generates three new translational theophylline riboswitch side products.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {861}, pmid = {30518404}, issn = {1756-0500}, support = {1613203//Division of Molecular and Cellular Biosciences/ ; 1613281//Division of Molecular and Cellular Biosciences/ ; }, abstract = {OBJECTIVE: The purpose of this project was to use an in vivo method to discover riboswitches that are activated by new ligands. We employed phage-assisted continuous evolution (PACE) to evolve new riboswitches in vivo. We started with one translational riboswitch and one transcriptional riboswitch, both of which were activated by theophylline. We used xanthine as the new target ligand during positive selection followed by negative selection using theophylline. The goal was to generate very large M13 phage populations that contained unknown mutations, some of which would result in new aptamer specificity. We discovered side products of three new theophylline translational riboswitches with different levels of protein production.

RESULTS: We used next generation sequencing to identify M13 phage that carried riboswitch mutations. We cloned and characterized the most abundant riboswitch mutants and discovered three variants that produce different levels of translational output while retaining their theophylline specificity. Although we were unable to demonstrate evolution of new riboswitch ligand specificity using PACE, we recommend careful design of recombinant M13 phage to avoid evolution of "cheaters" that short circuit the intended selection pressure.}, } @article {pmid30518402, year = {2018}, author = {Chee, J and Watson, MW and Chopra, A and Nguyen, B and Cook, AM and Creaney, J and Lesterhuis, WJ and Robinson, BW and Lee, YCG and Nowak, AK and Lake, RA and McDonnell, AM}, title = {Tumour associated lymphocytes in the pleural effusions of patients with mesothelioma express high levels of inhibitory receptors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {864}, pmid = {30518402}, issn = {1756-0500}, support = {CA150787//U.S. Department of Defense/ ; }, abstract = {OBJECTIVE: Pleural effusion (PE) is a common feature of malignant pleural mesothelioma. These effusions typically contain lymphocytes and malignant cells. We postulated that the PE would be a source of lymphocytes for analysis of tumor immune milieu. The aim of this study was to compare the phenotype and T cell receptor usage of pleural effusion T cells with paired concurrently drawn peripheral blood lymphocytes. We used multi-parameter flow cytometry and high-throughput T cell receptor sequencing to analyse peripheral blood and pleural effusion mononuclear cells.

RESULTS: Both CD8+ and CD4+ T cells from effusion showed increased expression of T cell inhibitory receptors PD-1, LAG-3 and Tim-3 compared to blood. Comprehensive T cell receptor sequencing on one of the patients showed a discordant distribution of clonotypes in the antigen-experienced (PD-1+) compartment between effusion and blood, suggesting an enrichment of antigen specific clonotypes in the effusion, with potential as an immunological response biomarker.}, } @article {pmid30518359, year = {2018}, author = {Cuscó, F and Cardador, L and Bota, G and Morales, MB and Mañosa, S}, title = {Inter-individual consistency in habitat selection patterns and spatial range constraints of female little bustards during the non-breeding season.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {56}, pmid = {30518359}, issn = {1472-6785}, support = {CGL2004-06147-C02-01/BOS//Ministerio de Ciencia y Tecnología/ ; CGL2009-13029/BOS//Ministerio de Ciencia e Innovación/ ; AP2010-2977//Ministerio de Educación, Cultura y Deporte/ ; 752149//H2020 Marie Skłodowska-Curie Actions/ ; }, abstract = {BACKGROUND: Identifying the factors that affect ranging behavior of animals is a central issue to ecology and an essential tool for designing effective conservation policies. This knowledge provides the information needed to predict the consequences of land-use change on species habitat use, especially in areas subject to major habitat transformations, such as agricultural landscapes. We evaluate inter-individual variation relative to environmental predictors and spatial constraints in limiting ranging behavior of female little bustards (Tetrax tetrax) in the non-breeding season. Our analyses were based on 11 females tracked with GPS during 5 years in northeastern Spain. We conducted deviance partitioning analyses based on different sets of generalized linear mixed models constructed with environmental variables and spatial filters obtained by eigenvector mapping, while controlling for temporal and inter-individual variation.

RESULTS: The occurrence probability of female little bustards in response to environmental variables and spatial filters within the non-breeding range exhibited inter-individual consistency. Pure spatial factors and joint spatial-habitat factors explained most of the variance in the models. Spatial predictors representing aggregation patterns at ~ 18 km and 3-5 km respectively had a high importance in female occurrence. However, pure habitat effects were also identified. Terrain slope, alfalfa, corn stubble and irrigated cereal stubble availability were the variables that most contributed to environmental models. Overall, models revealed a non-linear negative effect of slope and positive effects of intermediate values of alfalfa and corn stubble availability. High levels of cereal stubble in irrigated land and roads had also a positive effect on occurrence at the population level.

CONCLUSIONS: Our results provide evidence that female little bustard ranging behavior was spatially constrained beyond environmental variables during the non-breeding season. This pattern may result from different not mutually exclusive processes, such as cost-benefit balances of animal movement, configurational heterogeneity of environment or from high site fidelity and conspecific attraction. Measures aimed at keeping alfalfa availability and habitat heterogeneity in open landscapes and flat terrains, in safe places close to breeding grounds, could contribute to protect little bustard populations during the non-breeding season.}, } @article {pmid30518342, year = {2018}, author = {Brottier, L and Chaintreuil, C and Simion, P and Scornavacca, C and Rivallan, R and Mournet, P and Moulin, L and Lewis, GP and Fardoux, J and Brown, SC and Gomez-Pacheco, M and Bourges, M and Hervouet, C and Gueye, M and Duponnois, R and Ramanankierana, H and Randriambanona, H and Vandrot, H and Zabaleta, M and DasGupta, M and D'Hont, A and Giraud, E and Arrighi, JF}, title = {A phylogenetic framework of the legume genus Aeschynomene for comparative genetic analysis of the Nod-dependent and Nod-independent symbioses.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {333}, pmid = {30518342}, issn = {1471-2229}, support = {ANR-AeschyNod-14-CE19-0005-01//ANR/ ; }, mesh = {Biological Evolution ; Bradyrhizobium ; Fabaceae/*genetics/metabolism/physiology ; Genomics ; Nitrogen Fixation ; Phylogeny ; Plant Root Nodulation/genetics ; Ploidies ; Symbiosis/*genetics ; }, abstract = {BACKGROUND: Among semi-aquatic species of the legume genus Aeschynomene, some have the property of being nodulated by photosynthetic Bradyrhizobium lacking the nodABC genes necessary for the synthesis of Nod factors. Knowledge of the specificities underlying this Nod-independent symbiosis has been gained from the model legume Aeschynomene evenia but our understanding remains limited due to the lack of comparative genetics with related taxa using a Nod factor-dependent process. To fill this gap, we combined different approaches to perform a thorough comparative analysis in the genus Aeschynomene.

RESULTS: This study significantly broadened previous taxon sampling, including in allied genera, in order to construct a comprehensive phylogeny. In the phylogenetic tree, five main lineages were delineated, including a novel lineage, the Nod-independent clade and another one containing a polytomy that comprised several Aeschynomene groups and all the allied genera. This phylogeny was matched with data on chromosome number, genome size and low-copy nuclear gene sequences to reveal the diploid species and a polytomy containing mostly polyploid taxa. For these taxa, a single allopolyploid origin was inferred and the putative parental lineages were identified. Finally, nodulation tests with different Bradyrhizobium strains revealed new nodulation behaviours and the diploid species outside of the Nod-independent clade were compared for their experimental tractability and genetic diversity.

CONCLUSIONS: The extended knowledge of the genetics and biology of the different lineages sheds new light of the evolutionary history of the genus Aeschynomene and they provide a solid framework to exploit efficiently the diversity encountered in Aeschynomene legumes. Notably, our backbone tree contains all the species that are diploid and it clarifies the genetic relationships between the Nod-independent clade and the Nod-dependent lineages. This study enabled the identification of A. americana and A. patula as the most suitable species to undertake a comparative genetic study of the Nod-independent and Nod-dependent symbioses.}, } @article {pmid30518326, year = {2018}, author = {Gardiner, JD and Behnsen, J and Brassey, CA}, title = {Alpha shapes: determining 3D shape complexity across morphologically diverse structures.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {184}, pmid = {30518326}, issn = {1471-2148}, support = {BB/N010957/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; Fractals ; *Imaging, Three-Dimensional ; Male ; Penis/*anatomy & histology ; }, abstract = {BACKGROUND: Following recent advances in bioimaging, high-resolution 3D models of biological structures are now generated rapidly and at low-cost. To use this data to address evolutionary and ecological questions, an array of tools has been developed to conduct shape analysis and quantify topographic complexity. Here we focus particularly on shape techniques applied to irregular-shaped objects lacking clear homologous landmarks, and propose a new 'alpha-shapes' method for quantifying 3D shape complexity.

METHODS: We apply alpha-shapes to quantify shape complexity in the mammalian baculum as an example of a morphologically disparate structure. Micro- computed-tomography (μCT) scans of bacula were conducted. Bacula were binarised and converted into point clouds. Following application of a scaling factor to account for absolute size differences, a suite of alpha-shapes was fitted per specimen. An alpha shape is formed from a subcomplex of the Delaunay triangulation of a given set of points, and ranges in refinement from a very coarse mesh (approximating convex hulls) to a very fine fit. 'Optimal' alpha was defined as the refinement necessary in order for alpha-shape volume to equal CT voxel volume, and was taken as a metric of overall 'complexity'.

RESULTS: Our results show that alpha-shapes can be used to quantify interspecific variation in shape 'complexity' within biological structures of disparate geometry. The 'stepped' nature of alpha curves is informative with regards to the contribution of specific morphological features to overall 'complexity'. Alpha-shapes agrees with other measures of complexity (dissection index, Dirichlet normal energy) in identifying ursid bacula as having low shape complexity. However, alpha-shapes estimates mustelid bacula as being most complex, contrasting with other shape metrics. 3D fractal dimension is identified as an inappropriate metric of complexity when applied to bacula.

CONCLUSIONS: Alpha-shapes is used to calculate 'optimal' alpha refinement as a proxy for shape 'complexity' without identifying landmarks. The implementation of alpha-shapes is straightforward, and is automated to process large datasets quickly. We interpret alpha-shapes as being particularly sensitive to concavities in surface topology, potentially distinguishing it from other shape complexity metrics. Beyond genital shape, the alpha-shapes technique holds considerable promise for new applications across evolutionary, ecological and palaeoecological disciplines.}, } @article {pmid30518325, year = {2018}, author = {Gust, KA and Chaitankar, V and Ghosh, P and Wilbanks, MS and Chen, X and Barker, ND and Pham, D and Scanlan, LD and Rawat, A and Talent, LG and Quinn, MJ and Vulpe, CD and Elasri, MO and Johnson, MS and Perkins, EJ and McFarland, CA}, title = {Multiple environmental stressors induce complex transcriptomic responses indicative of phenotypic outcomes in Western fence lizard.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {877}, pmid = {30518325}, issn = {1471-2164}, support = {Army EQI-6.1, 09-27//U.S. Army/ ; Army EQI-6.2,6.3 BioNetworks//U.S. Army/ ; Army 6.1, 09-27//Engineer Research and Development Center/ ; }, abstract = {BACKGROUND: The health and resilience of species in natural environments is increasingly challenged by complex anthropogenic stressor combinations including climate change, habitat encroachment, and chemical contamination. To better understand impacts of these stressors we examined the individual- and combined-stressor impacts of malaria infection, food limitation, and 2,4,6-trinitrotoluene (TNT) exposures on gene expression in livers of Western fence lizards (WFL, Sceloporus occidentalis) using custom WFL transcriptome-based microarrays.

RESULTS: Computational analysis including annotation enrichment and correlation analysis identified putative functional mechanisms linking transcript expression and toxicological phenotypes. TNT exposure increased transcript expression for genes involved in erythropoiesis, potentially in response to TNT-induced anemia and/or methemoglobinemia and caused dose-specific effects on genes involved in lipid and overall energy metabolism consistent with a hormesis response of growth stimulation at low doses and adverse decreases in lizard growth at high doses. Functional enrichment results were indicative of inhibited potential for lipid mobilization and catabolism in TNT exposures which corresponded with increased inguinal fat weights and was suggestive of a decreased overall energy budget. Malaria infection elicited enriched expression of multiple immune-related functions likely corresponding to increased white blood cell (WBC) counts. Food limitation alone enriched functions related to cellular energy production and decreased expression of immune responses consistent with a decrease in WBC levels.

CONCLUSIONS: Despite these findings, the lizards demonstrated immune resilience to malaria infection under food limitation with transcriptional results indicating a fully competent immune response to malaria, even under bio-energetic constraints. Interestingly, both TNT and malaria individually increased transcriptional expression of immune-related genes and increased overall WBC concentrations in blood; responses that were retained in the TNT x malaria combined exposure. The results demonstrate complex and sometimes unexpected responses to multiple stressors where the lizards displayed remarkable resiliency to the stressor combinations investigated.}, } @article {pmid30518324, year = {2018}, author = {Nishihara, M and Higuchi, A and Watanabe, A and Tasaki, K}, title = {Application of the CRISPR/Cas9 system for modification of flower color in Torenia fournieri.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {331}, pmid = {30518324}, issn = {1471-2229}, support = {15H04453//Japanese Society for the Promotion of Science/ ; 16K18654//Japanese Society for the Promotion of Science/ ; }, mesh = {CRISPR-Associated Protein 9 ; *CRISPR-Cas Systems ; Color ; Flowers/anatomy & histology/*genetics ; Gene Editing/*methods ; Genes, Plant/genetics ; Lamiales/anatomy & histology/*genetics ; Plants, Genetically Modified ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: CRISPR/Cas9 technology is one of the most powerful and useful tools for genome editing in various living organisms. In higher plants, the system has been widely exploited not only for basic research, such as gene functional analysis, but also for applied research such as crop breeding. Although the CRISPR/Cas9 system has been used to induce mutations in genes involved in various plant developmental processes, few studies have been performed to modify the color of ornamental flowers. We therefore attempted to use this system to modify flower color in the model plant torenia (Torenia fournieri L.).

RESULTS: We attempted to induce mutations in the torenia flavanone 3-hydroxylase (F3H) gene, which encodes a key enzyme involved in flavonoid biosynthesis. Application of the CRISPR/Cas9 system successfully generated pale blue (almost white) flowers at a high frequency (ca. 80% of regenerated lines) in transgenic torenia T0 plants. Sequence analysis of PCR amplicons by Sanger and next-generation sequencing revealed the occurrence of mutations such as base substitutions and insertions/deletions in the F3H target sequence, thus indicating that the obtained phenotype was induced by the targeted mutagenesis of the endogenous F3H gene.

CONCLUSIONS: These results clearly demonstrate that flower color modification by genome editing with the CRISPR/Cas9 system is easily and efficiently achievable. Our findings further indicate that this system may be useful for future research on flower pigmentation and/or functional analyses of additional genes in torenia.}, } @article {pmid30518323, year = {2018}, author = {Legesse, A and Abayneh, T and Mamo, G and Gelaye, E and Tesfaw, L and Yami, M and Belay, A}, title = {Molecular characterization of Mannheimia haemolytica isolates associated with pneumonic cases of sheep in selected areas of Central Ethiopia.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {205}, pmid = {30518323}, issn = {1471-2180}, abstract = {BACKGROUND: Mannheimia haemolytica has been recognized as the principal cause of pneumonic pasteurellosis in sheep and goats. It is one of the important diseases of small ruminants in Ethiopia. While annual vaccination using a monovalent vaccine (inactivated Pasteurella multocida biotype A) is common, respiratory diseases are still reported in various parts of Ethiopia. This suggests the need for further investigation into the species and strains responsible for the disease, which is vital information for development of a multivalent vaccine. The objective of the current study was to isolate M. heamolytica associated with pneumonic cases of sheep in selected areas of Central Ethiopia, determine its role and the strains/genotypes of the bacterium circulating in the study area.

RESULTS: Bacteriological analysis of nasal swab samples collected from a total of 76 pneumonic cases of sheep showed that M. haemolytica was isolated from 26 of them while B.trehalosi from two cases. Further molecular analyses of the isolates using M. haemolytica species-specific and M.haemolytica serotype-1 antigen specific PCR assays revealed, 26 of the isolates were identified as M. haemolytica of which 21 of them were M. haemolytica serotype-1. Both M. haemolytica and B.trehalosi isolates were not detected in a PCR assay targeting capsular biosynthesis gene (capA) of P.multocida despite the non-specific products observed in M. haemolytica isolates. Phylogenetic analysis of M. haemolytica isolates included in this study in comparison with the reference strains with respect to PHSSA and Rpt2 genes revealed that the Ethiopian M. haemolytica isolates constituted three distinct genotypes consistent with site of origin.

CONCLUSION: The study indicated that M.haemolytica is commonly associated with cases of pneumonia in sheep in the study areas of central Ethiopia although the remaining other pathogens responsible for majority of the cases are yet to be determined. Molecular characterization revealed the existence of three genotypes of M. haemolytica circulating in the study areas consistent to the site of isolation. The findings suggest further extensive work to determine all pathogens associated with sheep pneumonia and the strain distribution of M. heamolytica to understand its molecular epidemiology at national level and design cost effective prevention and control methods.}, } @article {pmid30518322, year = {2018}, author = {Yuenyong, W and Chinpongpanich, A and Comai, L and Chadchawan, S and Buaboocha, T}, title = {Downstream components of the calmodulin signaling pathway in the rice salt stress response revealed by transcriptome profiling and target identification.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {335}, pmid = {30518322}, issn = {1471-2229}, support = {BRG5680019//Thailand Research Fund/ ; PHD/0043/2556 - 4.C.CU/56/G.1.O.XX//Thailand Research Fund/ ; }, mesh = {Calmodulin/*metabolism/physiology ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant/genetics ; Oryza/genetics/*metabolism ; Plants, Genetically Modified ; Salt Stress ; Salt Tolerance/genetics ; *Signal Transduction ; }, abstract = {BACKGROUND: Calmodulin (CaM) is an important calcium sensor protein that transduces Ca2+ signals in plant stress signaling pathways. A previous study has revealed that transgenic rice over-expressing the calmodulin gene OsCam1-1 (LOC_Os03g20370) is more tolerant to salt stress than wild type. To elucidate the role of OsCam1-1 in the salt stress response mechanism, downstream components of the OsCam1-1-mediated response were identified and investigated by transcriptome profiling and target identification.

RESULTS: Transcriptome profiling of transgenic 'Khao Dawk Mali 105' rice over-expressing OsCam1-1 and wild type rice showed that overexpression of OsCam1-1 widely affected the expression of genes involved in several cellular processes under salt stress, including signaling, hormone-mediated regulation, transcription, lipid metabolism, carbohydrate metabolism, secondary metabolism, photosynthesis, glycolysis, tricarboxylic acid (TCA) cycle and glyoxylate cycle. Under salt stress, the photosynthesis rate in the transgenic rice was slightly lower than in wild type, while sucrose and starch contents were higher, suggesting that energy and carbon metabolism were affected by OsCam1-1 overexpression. Additionally, four known and six novel CaM-interacting proteins were identified by cDNA expression library screening with the recombinant OsCaM1. GO terms enriched in their associated proteins that matched those of the differentially expressed genes affected by OsCam1-1 overexpression revealed various downstream cellular processes that could potentially be regulated by OsCaM1 through their actions.

CONCLUSIONS: The diverse cellular processes affected by OsCam1-1 overexpression and possessed by the identified CaM1-interacting proteins corroborate the notion that CaM signal transduction pathways compose a complex network of downstream components involved in several cellular processes. These findings suggest that under salt stress, CaM activity elevates metabolic enzymes involved in central energy pathways, which promote or at least maintain the production of energy under the limitation of photosynthesis.}, } @article {pmid30518320, year = {2018}, author = {Mai, W and Xue, X and Feng, G and Tian, C}, title = {Simultaneously maximizing root/mycorrhizal growth and phosphorus uptake by cotton plants by optimizing water and phosphorus management.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {334}, pmid = {30518320}, issn = {1471-2229}, support = {U1403285//National Natural Science Foundation of China-Xinjiang Joint Fund (CN)/ ; }, mesh = {Crop Production/*methods ; Gossypium/*growth & development/metabolism/microbiology ; Mycorrhizae/*growth & development ; Phosphorus/administration & dosage/*metabolism ; Plant Roots/*growth & development/microbiology ; Soil ; Water/administration & dosage/*metabolism ; }, abstract = {BACKGROUND: There are two plant phosphorus (P)-uptake pathways, namely the direct P uptake by roots and the indirect P uptake through arbuscular mycorrhizal fungi (AMF). Maximizing the efficiency of root and AMF processes associated with P acquisition by adjusting soil conditions is important for simultaneously ensuring high yields and the efficient use of available P.

RESULTS: A root box experiment was conducted in 2015 and 2016. The aim was to investigate the effects of different P and soil water conditions on root/mycorrhizal growth and P uptake by cotton plants. Hyphal growth was induced in well-watered soil, but decreased with increasing P concentrations. Additionally, P fertilizers regulated root length only under well-watered conditions, with the longest roots observed in response to 0.2 g P2O5 kg- 1. In contrast, root elongation was essentially unaffected by P fertilizers under drought conditions. And soil water in general had more significant effects on root and hyphal growth than phosphorus levels. In well-watered soil, the application of P significantly increased the cotton plant P uptake, but there were no differences between the effects of 0.2 and 1 g P2O5 kg- 1. So optimizing phosphorus inputs and soil water can increase cotton growth and phosphorus uptake by maximizing the efficiency of phosphorus acquisition by roots/mycorrhizae.

CONCLUSIONS: Soil water and P contents of 19-24% and 20-25 mg kg- 1, respectively, simultaneously maximized root/mycorrhizal growth and P uptake by cotton plants.}, } @article {pmid30518319, year = {2018}, author = {Xu, SQ and Zhang, Y and Wang, P and Liu, W and Wu, XB and Zhou, JY}, title = {A statistical measure for the skewness of X chromosome inactivation based on family trios.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {109}, pmid = {30518319}, issn = {1471-2156}, support = {81773544//National Natural Science Foundation of China (CN)/ ; 81373098//National Natural Science Foundation of China (CN)/ ; 81573207//National Natural Science Foundation of China (CN)/ ; 201612121017//National and Guangzhou University Students' Innovation and Enterprise Training Project of China/ ; }, abstract = {BACKGROUND: X chromosome inactivation (XCI) is an important gene regulation mechanism in females to equalize the expression levels of X chromosome between two sexes. Generally, one of two X chromosomes in females is randomly chosen to be inactivated. Nonrandom XCI (XCI skewing) is also observed in females, which has been reported to play an important role in many X-linked diseases. However, there is no statistical measure available for the degree of the XCI skewing based on family data in population genetics.

RESULTS: In this article, we propose a statistical approach to measure the degree of the XCI skewing based on family trios, which is represented by a ratio of two genotypic relative risks in females. The point estimate of the ratio is obtained from the maximum likelihood estimates of two genotypic relative risks. When parental genotypes are missing in some family trios, the expectation-conditional-maximization algorithm is adopted to obtain the corresponding maximum likelihood estimates. Further, the confidence interval of the ratio is derived based on the likelihood ratio test. Simulation results show that the likelihood-based confidence interval has an accurate coverage probability under the situations considered. Also, we apply our proposed method to the rheumatoid arthritis data from USA for its practical use, and find out that a locus, rs2238907, may undergo the XCI skewing against the at-risk allele. But this needs to be further confirmed by molecular genetics.

CONCLUSIONS: The proposed statistical measure for the skewness of XCI is applicable to complete family trio data or family trio data with some paternal genotypes missing. The likelihood-based confidence interval has an accurate coverage probability under the situations considered. Therefore, our proposed statistical measure is generally recommended in practice for discovering the potential loci which undergo the XCI skewing.}, } @article {pmid30518318, year = {2018}, author = {Vieira, VMNCS and Engelen, AH and Huanel, OR and Guillemin, ML}, title = {Differentiation of haploid and diploid fertilities in Gracilaria chilensis affect ploidy ratio.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {183}, pmid = {30518318}, issn = {1471-2148}, mesh = {Analysis of Variance ; *Diploidy ; Gracilaria/*genetics/*physiology ; *Haploidy ; Probability ; Spores ; }, abstract = {BACKGROUND: Algal isomorphic biphasic life cycles alternate between free-living diploid (tetrasporophytes) and haploid (dioicious gametophytes) phases and the hypotheses explaining their maintenance are still debated. Classic models state that conditional differentiation between phases is required for the evolutionary stability of biphasic life cycles while other authors proposed that the uneven ploidy abundances observed in the field are explained by their cytological differences in spore production.

RESULTS: We monitored the state and fate of individuals of the red seaweed Gracilaria chilensis periodically for 3 years in five intertidal pools from two sites with distinct conditions. We tested for differentiation in fecundity and spore survival among the gametophyte males and females (haploids) and the tetrasporophytes (diploids). We tested for the influence of fecundity and spore survival on the observed uneven ploidy abundances in recruits. The probability of a frond becoming fecund was size-dependent, highest for the haploid males and lowest for the haploid females, with the diploids displaying intermediate probabilities. Fecund diploids released more tetraspores than carpospores released by the haploid females. Spore survival depended on ploidy and on the local density of co-habiting adult fronds. An advantage of diploid over haploid germlings was observed at very low and very high adult fronds densities.

CONCLUSIONS: Neither spore production nor spore survival determined the highly variable ploidy ratio within G. chilensis recruits. This result invalidates the hypothesis of natural cytological differences in spore production as the only driver of uneven field ploidy abundances in this species. Diploid spores (carpospores) survived better than haploid spores (tetraspores), especially in locations and time periods that were associated with the occurrence of strong biotic and abiotic stressors. We hypothesise that carpospore survival is higher due to support by their haploid female progenitors passing-on nutrients and chemical compounds improving survival under stressful conditions.}, } @article {pmid30518317, year = {2018}, author = {Read, TD and Petit, RA and Yin, Z and Montgomery, T and McNulty, MC and David, MZ}, title = {USA300 Staphylococcus aureus persists on multiple body sites following an infection.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {206}, pmid = {30518317}, issn = {1471-2180}, support = {AI095361-01//National Institute of Allergy and Infectious Diseases/ ; AI121860//National Institutes of Health/ ; }, abstract = {BACKGROUND: USA300 methicillin-resistant Staphylococcus aureus (MRSA) is a community- and hospital-acquired pathogen that frequently causes infections but also can survive on the human body asymptomatically as a part of the normal microbiota. We devised a comparative genomic strategy to track colonizing USA300 at different body sites after an initial infection. We sampled ST8 S. aureus from subjects at the site of a first known MRSA infection. Within 60 days of this infection and again 12 months later, each subject was tested for asymptomatic colonization in the nose, throat and perirectal region. 93 S. aureus strains underwent whole genome shotgun sequencing.

RESULTS: Among 28 subjects at the initial sampling time, we isolated S. aureus from the nose, throat and perirectal sites from 15, 11 and 15 of them, respectively. Twelve months later we isolated S. aureus from 9 subjects, with 6, 3 and 3 strains from the nose, throat and perirectal area, respectively. Genome sequencing revealed that 23 patients (ages 0-66 years) carried USA300 intra-subject lineages (ISLs), defined as having an index infection isolate and closely related colonizing strains. Pairwise distance between strains in different ISLs was 48 to 162 single nucleotide polymorphisms (SNPs) across the core regions of the chromosome, whereas within the same ISL it was 0 to 26 SNPs. Strains in ISLs from the same subject differed in plasmid and prophage content, and contained deletions that removed the mecA-containing SCCmec and ACME regions. Five strains contained frameshift mutations in agr toxin-regulating genes. Persistence of an ISL was not associated with clinical or demographic subject characteristics. We inferred that colonization with the ISL occurred about 18 weeks before the first assessment of asymptomatic colonization.

CONCLUSIONS: Clonal lineages of USA300 may continue to colonize people at one or more anatomic sites up to a year after an initial infection and experience loss of the SCCmec, loss and gain of other mobile genetic elements, and mutations in the agr operon.}, } @article {pmid30518316, year = {2018}, author = {Kouidri, A and Baumann, U and Okada, T and Baes, M and Tucker, EJ and Whitford, R}, title = {Wheat TaMs1 is a glycosylphosphatidylinositol-anchored lipid transfer protein necessary for pollen development.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {332}, pmid = {30518316}, issn = {1471-2229}, mesh = {Abscisic Acid/metabolism ; Flowers/growth & development/metabolism ; Gene Expression Profiling ; Glycosylphosphatidylinositols/*metabolism ; Indoleacetic Acids/metabolism ; Lipid Metabolism/*genetics ; Plant Growth Regulators/metabolism ; Plant Proteins/*genetics/metabolism ; Pollen/genetics/*growth & development ; Real-Time Polymerase Chain Reaction ; Transcription Factors/*genetics/metabolism ; Triticum/*genetics/metabolism ; }, abstract = {BACKGROUND: In flowering plants, lipid biosynthesis and transport within anthers is essential for male reproductive success. TaMs1, a dominant wheat fertility gene located on chromosome 4BS, has been previously fine mapped and identified to encode a glycosylphosphatidylinositol (GPI)-anchored non-specific lipid transfer protein (nsLTP). Although this gene is critical for pollen exine development, details of its function remains poorly understood.

RESULTS: In this study, we report that TaMs1 is only expressed from the B sub-genome, with highest transcript abundance detected in anthers containing microspores undergoing pre-meiosis through to meiosis. β-glucuronidase transcriptional fusions further revealed that TaMs1 is expressed throughout all anther cell-types. TaMs1 was identified to be expressed at an earlier stage of anther development relative to genes reported to be necessary for sporopollenin precursor biosynthesis. In anthers missing a functional TaMs1 (ms1c deletion mutant), these same genes were not observed to be mis-regulated, indicating an independent function for TaMs1 in pollen development. Exogenous hormone treatments on GUS reporter lines suggest that TaMs1 expression is increased by both indole-3-acetic acid (IAA) and abscisic acid (ABA). Translational fusion constructs showed that TaMs1 is targeted to the plasma membrane.

CONCLUSIONS: In summary, TaMs1 is a wheat fertility gene, expressed early in anther development and encodes a GPI-LTP targeted to the plasma membrane. The work presented provides a new insight into the process of wheat pollen development.}, } @article {pmid30508632, year = {2019}, author = {Miranda, NEO and Maciel, NM and Lima-Ribeiro, MS and Colli, GR and Haddad, CFB and Collevatti, RG}, title = {Diversification of the widespread neotropical frog Physalaemus cuvieri in response to Neogene-Quaternary geological events and climate dynamics.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {67-80}, doi = {10.1016/j.ympev.2018.11.003}, pmid = {30508632}, issn = {1095-9513}, abstract = {Here we reconstructed the demographical history and the dispersal dynamics of Physalemus cuvieri through the Neogene-Quaternary periods by coupling DNA regions with different mutation rates, ecological niche modelling, reconstruction of spatio-temporal lineage dispersal and coalescent simulations. Still, to test alternative diversification scenarios we used approximate Bayesian computation. Molecular phylogenetic analysis recovered four deep and strongly supported clades, which we interpret as population lineages. The ancestral location reconstruction placed the root in southcentral Amazonia, and the dispersal events indicate that spatial displacement was widespread early in the diversification of this species. The demographical scenario of "Multiple Refugia" with recent lineage admixture was the most likely hypothesis to predict the observed genetic parameters of P. cuvieri. Our results revealed that Neogene orogenic events might have played a prominent role in the early diversification of P. cuvieri. The species shows deep divergences with strong regional population structure, despite its widespread distribution. Final uplift of the central Brazilian Plateau and formation of the river basins in Central South America played an important role in the origin, diversification and the maintenance of P. cuvieri lineages.}, } @article {pmid30508631, year = {2019}, author = {Zhao, Z and Hu, J and Chen, S and Luo, Z and Luo, D and Wen, J and Tu, T and Zhang, D}, title = {Evolution of CYCLOIDEA-like genes in Fabales: Insights into duplication patterns and the control of floral symmetry.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {81-89}, doi = {10.1016/j.ympev.2018.11.007}, pmid = {30508631}, issn = {1095-9513}, abstract = {Cycloidea-like (CYC-like) genes are the key regulatory factors in the development of flower symmetry. Duplication and/or reduction of CYC-like genes have occurred several times in various angiosperm groups and are hypothesized to be correlated with the evolution of flower symmetry, which in turn has contributed to the evolutionary success of these groups. However, less is known about the evolutionary scenario of CYC-like genes in the whole Fabales, which contains four families with either symmetric or actinomorphic flowers. Here we investigated the evolution of CYC-like genes in all the four families of Fabales and recovered one to nine CYC-like genes (CYC1, CYC2, and CYC3) depending on which lineages, but the CYC3 genes were most likely lost in the ancestor of Leguminosae. Phylogenetic analysis suggested that the CYC-like genes could have undergone multiple duplications and losses in different plant lineages and formed distinct paralogous/orthologous clades. The ancestor of the Papilionoideae and Caesalpinioideae may possess two paralogs of CYC1 genes but one of them was subsequently lost in Papilionoideae and was retained only in several species of Caesalpinioideae. CYC2 genes were more frequently duplicated in Papilionoideae than in other legumes. We propose that the diversification patterns of both CYC1 and CYC2 genes are not related to the floral symmetry in non-papilionoid Fabales groups, however, gene duplication and functional divergence of CYC2 are essential for the floral zygomorphy of Papilionoideae. This is the first systematic analysis of the CYC-like genes in Fabales and could form the basis for further study of molecular mechanisms controlling floral symmetry in non-model plants of Fabales.}, } @article {pmid30508630, year = {2019}, author = {Ibañez, AC and Moré, M and Salazar, G and Leiva, S and Barboza, GE and Cocucci, AA}, title = {Crescendo, diminuendo and subito of the trumpets: winds of change in the concerted evolution between flowers and pollinators in Salpichroa (Solanaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {90-99}, doi = {10.1016/j.ympev.2018.11.020}, pmid = {30508630}, issn = {1095-9513}, abstract = {'Gradual' vs 'punctuated' and 'unidirectional' (only lengthening) vs. 'bidirectional'(lengthenings and shortenings) modes of evolution are explanations that compete to explain adaptive changes of flower tube length in angiosperm. The nightshade genus Salpichroa Miers, with 21 species mostly growing in the tropical Andes of southern South America, has the opportune qualities of including nearly 15-fold inter-specific variation in corolla tube length, as well as one species that is a candidate for participating in evolutionary escalation with the longest-billed hummingbird, Ensifera ensifera. We reconstructed the phylogenetic relationships using five molecular markers, the two plastid markers trnD-trnT and trnL, and three nuclear markers, ITS and two COSII, and estimated divergence times of the genus in order to reconstruct the history of both corolla tube length and pollination mode (i.e. hummingbirds, moths or multiple). We used comparative methods to determine whether corolla tube elongation/shortening is associated with shifts in pollination mode and to test, modes and rates of corolla tube change. We found evidence of both lengthening and shortening of corolla tubes. Evolutionary rates are consistent with rapid corolla tube length transitions that are only partly associated with shifts in pollination mode. Though 'punctuated' evolution (i.e. large changes predominantly at speciation events) explained corolla changes in the whole genus, 'gradual' evolution (i.e. gradual changes during a coevolutionary race with the same pollinator) was a better explanation for the change in the long-flowered clade, mostly pollinated by hummingbirds.}, } @article {pmid30508494, year = {2018}, author = {Kramer, G and Shiber, A and Bukau, B}, title = {Mechanisms of Cotranslational Maturation of Newly Synthesized Proteins.}, journal = {Annual review of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-biochem-013118-111717}, pmid = {30508494}, issn = {1545-4509}, abstract = {The timely production of functional proteins is of critical importance for the biological activity of cells. To reach the functional state, newly synthesized polypeptides have to become enzymatically processed, folded, and assembled into oligomeric complexes and, for noncytosolic proteins, translocated across membranes. Key activities of these processes occur cotranslationally, assisted by a network of machineries that transiently engage nascent polypeptides at distinct phases of translation. The sequence of events is tuned by intrinsic features of the nascent polypeptides and timely association of factors with the translating ribosome. Considering the dynamics of translation, the heterogeneity of cellular proteins, and the diversity of interaction partners, it is a major cellular achievement that these processes are temporally and spatially so precisely coordinated, minimizing the generation of damaged proteins. This review summarizes the current progress we have made toward a comprehensive understanding of the cotranslational interactions of nascent chains, which pave the way to their functional state. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30507072, year = {2018}, author = {Sirois, SH and Buckley, DH}, title = {Factors governing extracellular DNA degradation dynamics in soil.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12725}, pmid = {30507072}, issn = {1758-2229}, support = {DE-SC0004486//U.S. Department of Energy, Office of Biological & Environmental Research Genomic Science Program/ ; DE-SC0016364//U.S. Department of Energy, Office of Biological & Environmental Research Genomic Science Program/ ; 1010520//USDA National Institute of Food and Agriculture, Hatch Project/ ; }, abstract = {We examined the impacts of soil moisture, temperature, agricultural management and habitat type on the degradation dynamics of eDNA in soils. Synthetic eDNA was added to soil microcosms, and its disappearance over time was measured using both high-throughput sequencing and qPCR. The synthetic eDNA was degraded rapidly, but a small fraction remained detectable throughout the experiments (39-80 days). The eDNA degradation rate was positively correlated with moisture and temperature, but negatively correlated with soil organic carbon content. End-point stabilization of eDNA was highest at low moisture and temperature, but exhibited no relationship with soil organic carbon. Tilled soils had higher rates of degradation and less stabilization than no-till soils. Among different habitats we observed that forest soils had the slowest degradation rate, and meadow soils had the greatest stabilization of eDNA. While eDNA was detectable by qPCR in all treatments across all time-points, it became inconsistently detectable with high-throughput gene sequencing in less than 1 week. We conclude that eDNA degradation and stabilization dynamics vary with moisture, temperature and habitat characteristics, that small amounts of eDNA may persist in soils indefinitely, and that the ability of persistent eDNA to impact microbial community estimates depends on method sensitivity and experimental objectives.}, } @article {pmid30507071, year = {2018}, author = {Alsammar, HF and Naseeb, S and Brancia, LB and Gilman, RT and Wang, P and Delneri, D}, title = {Targeted metagenomics approach to capture the biodiversity of Saccharomyces genus in wild environments.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12724}, pmid = {30507071}, issn = {1758-2229}, support = {//Kuwait University/ ; BB/L021471/1//BBSRC/ ; 767015//European Union's Horizon 2020 research and innovation programme/ ; }, abstract = {The species of the genus Saccharomyces are commonly inhabiting tree bark and the surrounding soil, but their abundance have likely been underestimated due to biases in culturing methods. Metagenomic studies have so far been unable to detect Saccharomyces species in wild environments. Here, we sequenced the mycobiome of soils surrounding different trees at various altitudes in the Italian Alps. To survey for yeasts species belonging to Saccharomyces genus rather than other fungal species, we performed a selectivity step involving the isolation of the internal transcribed spacer (ITS) region that is specific to this yeast group. Reads mapping to Saccharomyces species were detected in all soil samples, including reads for S. mikatae and for S. eubayanus. ITS1 alignment of the S. cerevisiae, S. paradoxus and S. kudriavzevii sequences showed up to three base pair polymorphisms with other known strains, indicating possible new lineages. Basidiomycetous fungi were still the dominant species, compared to the Ascomycota, but the selectivity step allowed for the first time the detection and study of the biodiversity of the Saccharomyces species in their natural environment.}, } @article {pmid30507067, year = {2018}, author = {Parkes, RJ and Berlendis, S and Roussel, EG and Bahruji, H and Webster, G and Oldroyd, A and Weightman, AJ and Bowker, M and Davies, PR and Sass, H}, title = {Rock-crushing derived hydrogen directly supports a methanogenic community: significance for the deep biosphere.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12723}, pmid = {30507067}, issn = {1758-2229}, support = {NE/H02042X/1//Natural Environment Research Council/ ; NE/J011177/1//Natural Environment Research Council/ ; }, abstract = {Microbial populations exist to great depths on Earth, but with apparently insufficient energy supply. Earthquake rock fracturing produces H2 from mechanochemical water splitting, however, microbial utilization of this widespread potential energy source has not been directly demonstrated. Here, we show experimentally that mechanochemically generated H2 from granite can be directly, long-term, utilized by a CH4 producing microbial community. This is consistent with CH4 formation in subsurface rock fracturing in the environment. Our results not only support water splitting H2 generation as a potential deep biosphere energy source, but as an oxidant must also be produced, they suggest that there is also a respiratory oxidant supply in the subsurface which is independent of photosynthesis. This may explain the widespread distribution of facultative aerobes in subsurface environments. A range of common rocks were shown to produce mechanochemical H2 , and hence, this process should be widespread in the subsurface, with the potential for considerable mineral fuelled CH4 production.}, } @article {pmid30507060, year = {2018}, author = {Gerphagnon, M and Agha, R and Martin-Creuzburg, D and Bec, A and Perriere, F and Rad-Menéndez, C and Gachon, CMM and Wolinska, J}, title = {Comparison of sterol and fatty acid profiles of chytrids and their hosts reveals trophic upgrading of nutritionally inadequate phytoplankton by fungal parasites.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14489}, pmid = {30507060}, issn = {1462-2920}, support = {//Leibniz-Institute of Freshwater Ecology and Inland Fisheries (IGB), Germany. International IGB Fellowship Program, Freshwater Science/ ; //Alexander von Humboldt Foundation/ ; }, abstract = {Chytrids are ubiquitous fungal parasites in aquatic ecosystems, infecting representatives of all major phytoplankton groups. They repack carbon from inedible phytoplankton hosts into easily ingested chytrid propagules (zoospores), rendering this carbon accessible to zooplankton. Grazing on zoospores may circumvent bottlenecks in carbon transfer imposed by the dominance of inedible or poorly nutritious phytoplankton (mycoloop). We explored qualitative aspects of the mycoloop by analysing lipid profiles (fatty acids, sterols) of two chytrids infecting two major bloom-forming phytoplankton taxa of contrasting nutritional value: the diatom Asterionella formosa and the filamentous cyanobacterium Planktothrix agardhii. The polyunsaturated fatty acid composition of chytrids largely reflected that of their hosts, highlighting their role as conveyors of otherwise inaccessible essential lipids to higher trophic levels. We also showed that chytrids are capable of synthesizing sterols, thus providing a source of these essential nutrients for grazers even when sterols are absent in their phytoplankton hosts. Our findings reveal novel qualitative facets of the mycoloop, showing that parasitic chytrids, in addition to making carbon and essential lipids available from inedible sources, also upgrade their host's biochemical composition by producing sterols de novo, thereby enhancing carbon and energy fluxes in aquatic food webs.}, } @article {pmid30507059, year = {2018}, author = {Hammarlund, SP and Chacón, JM and Harcombe, WR}, title = {A shared limiting resource leads to competitive exclusion in a cross-feeding system.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14493}, pmid = {30507059}, issn = {1462-2920}, support = {GM121498-01A1//National Institutes of Health/ ; }, abstract = {Species interactions and coexistence are often dependent upon environmental conditions. When two cross-feeding bacteria exchange essential nutrients, the addition of a cross-fed nutrient to the environment can release one species from its dependence on the other. Previous studies suggest that continued coexistence depends on relative growth rates: coexistence is maintained if the slower-growing species is released from its dependence on the other, but if the faster-growing species is released, the slower-growing species will be lost (a hypothesis that we call 'feed the faster grower' or FFG). Using invasion-from-rare experiments with two reciprocally cross-feeding bacteria, genome-scale metabolic modelling and classical ecological models, we explored the potential for coexistence when one cross-feeder became independent. We found that whether nutrient addition shifted an interaction from mutualism to commensalism or parasitism depended on whether the nutrient that limited total growth was required by one or both species. Parasitism resulted when both species required the growth-limiting resource. Importantly, coexistence was only lost when the interaction became parasitism, and the obligate species had a slower growth rate. Under these restricted conditions, the FFG hypothesis applied. Our results contribute to a mechanistic understanding of how resources can be manipulated to alter interactions and coexistence in microbial communities.}, } @article {pmid30507058, year = {2018}, author = {Kurm, V and Geisen, S and Gera Hol, WH}, title = {A low proportion of rare bacterial taxa responds to abiotic changes compared with dominant taxa.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14492}, pmid = {30507058}, issn = {1462-2920}, abstract = {In many studies, rare bacterial taxa have been found to increase in response to environmental changes. These changes have been proposed to contribute to the insurance of ecosystem functions. However, it has not been systematically tested if rare taxa are more likely to increase in abundance than dominant taxa. Here, we study whether rare soil bacterial taxa are more likely to respond to environmental disturbances and if rare taxa are more opportunistic than dominant taxa. To test this, we applied nine different disturbance treatments to a grassland soil and observed changes in bacterial community composition over 7 days. While 12% of the dominant taxa changed in abundance, only 1% of the rare taxa showed any effect. Rare taxa increased in response to a single disturbance treatment only, while dominant taxa responded to up to five treatments. We conclude that rare taxa are not more likely to contribute to community dynamics after disturbances than dominant taxa. Nevertheless, as rare taxa outnumber abundant taxa with here 230 taxa that changed significantly, the chance is high that some of these rare taxa might act as ecologically important keystone taxa. Therefore, rare and abundant taxa might both contribute to ecosystem insurance.}, } @article {pmid30507057, year = {2018}, author = {Stal, LJ and Bolhuis, H and Cretoiu, MS}, title = {Phototrophic marine benthic microbiomes: the ecophysiology of these biological entities.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14494}, pmid = {30507057}, issn = {1462-2920}, abstract = {Phototrophic biofilms are multispecies, self-sustaining and largely closed microbial ecosystems. They form macroscopic structures such as microbial mats and stromatolites. These sunlight-driven consortia consist of a number of functional groups of microorganisms that recycle the elements internally. Particularly, the sulfur cycle is discussed in more detail as this is fundamental to marine benthic microbial communities and because recently exciting new insights have been obtained. The cycling of elements demands a tight tuning of the various metabolic processes and require cooperation between the different groups of microorganisms. This is likely achieved through cell-to-cell communication and a biological clock. Biofilms may be considered as a macroscopic biological entity with its own physiology. We review the various components of some marine phototrophic biofilms and discuss their roles in the system. The importance of extracellular polymeric substances (EPS) as the matrix for biofilm metabolism and as substrate for biofilm microorganisms is discussed. We particularly assess the importance of extracellular DNA, horizontal gene transfer and viruses for the generation of genetic diversity and innovation, and for rendering resilience to external forcing to these biological entities.}, } @article {pmid30505390, year = {2018}, author = {Fan, X and Tang, J and Nie, L and Huang, J and Wang, G}, title = {High-quality-draft genome sequence of the heavy metal resistant and exopolysaccharides producing bacterium Mucilaginibacter pedocola TBZ30T.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {34}, pmid = {30505390}, issn = {1944-3277}, abstract = {Mucilaginibacter pedocola TBZ30T (= CCTCC AB 2015301T = KCTC 42833T) is a Gram- negative, rod-shaped, non-motile and non-spore-forming bacterium isolated from a heavy metal contaminated paddy field. It shows resistance to multiple heavy metals and can adsorb/remove Zn2+ and Cd2+ during cultivation. In addition, strain TBZ30T produces exopolysaccharides (EPS). These features make it a great potential to bioremediate heavy metal contamination and biotechnical application. Here we describe the genome sequence and annotation of strain TBZ30T. The genome size is 7,035,113 bp, contains 3132 protein-coding genes (2736 with predicted functions), 50 tRNA encoding genes and 14 rRNA encoding genes. Putative heavy metal resistant genes and EPS associated genes are found in the genome.}, } @article {pmid30505389, year = {2018}, author = {Li, Y and Guo, XH and Dang, YR and Sun, LL and Zhang, XY and Chen, XL and Qin, QL and Wang, P}, title = {Complete genome sequence of Arcticibacterium luteifluviistationis SM1504T, a cytophagaceae bacterium isolated from Arctic surface seawater.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {33}, pmid = {30505389}, issn = {1944-3277}, abstract = {Arcticibacterium luteifluviistationis SM1504T was isolated from Arctic surface seawater and classified as a novel genus of the phylum Bacteroides. To date, no Arcticibacterium genomes have been reported, their genomic compositions and metabolic features are still unknown. Here, we reported the complete genome sequence of A. luteifluviistationis SM1504T, which comprises 5,379,839 bp with an average GC content of 37.20%. Genes related to various stress (such as radiation, osmosis and antibiotics) resistance and gene clusters coding for carotenoid and flexirubin biosynthesis were detected in the genome. Moreover, the genome contained a 245-kb genomic island and a 15-kb incomplete prophage region. A great percentage of proteins belonging to carbohydrate metabolism especially in regard to polysaccharides utilization were found. These related genes and metabolic characteristics revealed genetic basis for adapting to the diverse extreme Arctic environments. The genome sequence of A. luteifluviistationis SM1504T also implied that the genus Arcticibacterium may act as a vital organic carbon matter decomposer in the Arctic seawater ecosystem.}, } @article {pmid30504706, year = {2018}, author = {Ekici, C and Esener, Z and Korkmaz, S and Saltürk, N and Yüksel, S and Koç, A}, title = {A Rare Mosaic Karyotype of 45,X/46,X,psu idic(Y)(p11.32)/46,XY with SHOX Haploinsufficiency, External Male Genitalia, and Short Stature.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000495201}, pmid = {30504706}, issn = {1661-5433}, abstract = {In this case study, we describe a 3-year-old boy who was referred to the Inonu University Hospital with short stature complaint. His height was 86 cm (-2.96 SDS), weight was 12 kg (-2.43 SDS), and head circumference was 46.5 cm (-2.34 SDS). Chromosomal analyses were performed on cultured peripheral blood lymphocytes of the patient and his parents and showed the patient's karyotype mos 45,X[20]/46,X,idic(Y)(p11.32)[29]/46,XY[1]. The karyotypes of the parents were normal. Subsequently, specific FISH probes were hybridized to the related regions of the sex-determining region Y (SRY), centromere X/Y (CEP X/Y), and short stature homeobox (SHOX) genes. Simultaneous SNP array-CGH was conducted. As to our knowledge, we present the first patient with mosaic isodicentric Y chromosome with 3 different cell lines and normal male external genitalia. Our results suggest that it would be beneficial to study cytogenetic and molecular cytogenetic methods together for better diagnostic accuracy and treatment.}, } @article {pmid30504698, year = {2018}, author = {Backhouse, B and Hanna, C and Robevska, G and van den Bergen, J and Pelosi, E and Simons, C and Koopman, P and Juniarto, AZ and Grover, S and Faradz, S and Sinclair, A and Ayers, K and Tan, TY}, title = {Identification of Candidate Genes for Mayer-Rokitansky-Küster-Hauser Syndrome Using Genomic Approaches.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000494896}, pmid = {30504698}, issn = {1661-5433}, abstract = {Mayer-Rokitansky-Küster-Hauser (MRKH) syndrome is a disorder of sex development which affects 1 in 4,500 females and is characterized by agenesis of müllerian structures, including the uterus, cervix, and upper vagina. It can occur in isolation (type 1) or in conjunction with various anomalies (type 2), with a subset of these comprising müllerian, renal, and cervicothoracic abnormalities (MURCS) association. The genetic causes of MRKH have been investigated previously yielding limited results, with massive parallel sequencing becoming increasingly utilized. We sought to identify genetic contributions to MRKH using a combination of microarray and whole exome sequencing (WES) on a cohort of 8 unrelated women with MRKH and MURCS. WES data were analysed using a candidate gene approach to identify potential contributing variants. Microarray analysis identified a 0.6-Mb deletion in the previously implicated 16p11.2 region in a patient with MRKH type 2. WES revealed 16 rare nonsynonymous variants in MRKH candidate genes across the cohort. These included variants in several genes, such as LRP10 and DOCK4, associated with disorders with müllerian anomalies. Further functional studies of these variants will help to delineate their biological significance and expand the genotypic spectrum of MRKH.}, } @article {pmid30504145, year = {2018}, author = {Tokuda, G and Mikaelyan, A and Fukui, C and Matsuura, Y and Watanabe, H and Fujishima, M and Brune, A}, title = {Fiber-associated spirochetes are major agents of hemicellulose degradation in the hindgut of wood-feeding higher termites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11996-E12004}, doi = {10.1073/pnas.1810550115}, pmid = {30504145}, issn = {1091-6490}, abstract = {Symbiotic digestion of lignocellulose in wood-feeding higher termites (family Termitidae) is a two-step process that involves endogenous host cellulases secreted in the midgut and a dense bacterial community in the hindgut compartment. The genomes of the bacterial gut microbiota encode diverse cellulolytic and hemicellulolytic enzymes, but the contributions of host and bacterial symbionts to lignocellulose degradation remain ambiguous. Our previous studies of Nasutitermes spp. documented that the wood fibers in the hindgut paunch are consistently colonized not only by uncultured members of Fibrobacteres, which have been implicated in cellulose degradation, but also by unique lineages of Spirochaetes. Here, we demonstrate that the degradation of xylan, the major component of hemicellulose, is restricted to the hindgut compartment, where it is preferentially hydrolyzed over cellulose. Metatranscriptomic analysis documented that the majority of glycoside hydrolase (GH) transcripts expressed by the fiber-associated bacterial community belong to family GH11, which consists exclusively of xylanases. The substrate specificity was further confirmed by heterologous expression of the gene encoding the predominant homolog. Although the most abundant transcripts of GH11 in Nasutitermes takasagoensis were phylogenetically placed among their homologs of Firmicutes, immunofluorescence microscopy, compositional binning of metagenomics contigs, and the genomic context of the homologs indicated that they are encoded by Spirochaetes and were most likely obtained by horizontal gene transfer among the intestinal microbiota. The major role of spirochetes in xylan degradation is unprecedented and assigns the fiber-associated Treponema clades in the hindgut of wood-feeding higher termites a prominent part in the breakdown of hemicelluloses.}, } @article {pmid30504144, year = {2018}, author = {Beaune, G and Blanch-Mercader, C and Douezan, S and Dumond, J and Gonzalez-Rodriguez, D and Cuvelier, D and Ondarçuhu, T and Sens, P and Dufour, S and Murrell, MP and Brochard-Wyart, F}, title = {Spontaneous migration of cellular aggregates from giant keratocytes to running spheroids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12926-12931}, doi = {10.1073/pnas.1811348115}, pmid = {30504144}, issn = {1091-6490}, support = {U54 CA209992/CA/NCI NIH HHS/United States ; R01 GM126256/GM/NIGMS NIH HHS/United States ; }, abstract = {Despite extensive knowledge on the mechanisms that drive single-cell migration, those governing the migration of cell clusters, as occurring during embryonic development and cancer metastasis, remain poorly understood. Here, we investigate the collective migration of cell on adhesive gels with variable rigidity, using 3D cellular aggregates as a model system. After initial adhesion to the substrate, aggregates spread by expanding outward a cell monolayer, whose dynamics is optimal in a narrow range of rigidities. Fast expansion gives rise to the accumulation of mechanical tension that leads to the rupture of cell-cell contacts and the nucleation of holes within the monolayer, which becomes unstable and undergoes dewetting like a liquid film. This leads to a symmetry breaking and causes the entire aggregate to move as a single entity. Varying the substrate rigidity modulates the extent of dewetting and induces different modes of aggregate motion: "giant keratocytes," where the lamellipodium is a cell monolayer that expands at the front and retracts at the back; "penguins," characterized by bipedal locomotion; and "running spheroids," for nonspreading aggregates. We characterize these diverse modes of collective migration by quantifying the flows and forces that drive them, and we unveil the fundamental physical principles that govern these behaviors, which underscore the biological predisposition of living material to migrate, independent of length scale.}, } @article {pmid30504143, year = {2018}, author = {Romero Romero, ML and Yang, F and Lin, YR and Toth-Petroczy, A and Berezovsky, IN and Goncearenco, A and Yang, W and Wellner, A and Kumar-Deshmukh, F and Sharon, M and Baker, D and Varani, G and Tawfik, DS}, title = {Simple yet functional phosphate-loop proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11943-E11950}, doi = {10.1073/pnas.1812400115}, pmid = {30504143}, issn = {1091-6490}, support = {R01 GM103834/GM/NIGMS NIH HHS/United States ; R35 GM126942/GM/NIGMS NIH HHS/United States ; }, abstract = {Abundant and essential motifs, such as phosphate-binding loops (P-loops), are presumed to be the seeds of modern enzymes. The Walker-A P-loop is absolutely essential in modern NTPase enzymes, in mediating binding, and transfer of the terminal phosphate groups of NTPs. However, NTPase function depends on many additional active-site residues placed throughout the protein's scaffold. Can motifs such as P-loops confer function in a simpler context? We applied a phylogenetic analysis that yielded a sequence logo of the putative ancestral Walker-A P-loop element: a β-strand connected to an α-helix via the P-loop. Computational design incorporated this element into de novo designed β-α repeat proteins with relatively few sequence modifications. We obtained soluble, stable proteins that unlike modern P-loop NTPases bound ATP in a magnesium-independent manner. Foremost, these simple P-loop proteins avidly bound polynucleotides, RNA, and single-strand DNA, and mutations in the P-loop's key residues abolished binding. Binding appears to be facilitated by the structural plasticity of these proteins, including quaternary structure polymorphism that promotes a combined action of multiple P-loops. Accordingly, oligomerization enabled a 55-aa protein carrying a single P-loop to confer avid polynucleotide binding. Overall, our results show that the P-loop Walker-A motif can be implemented in small and simple β-α repeat proteins, primarily as a polynucleotide binding motif.}, } @article {pmid30504142, year = {2018}, author = {Bosco, DA}, title = {Translation dysregulation in neurodegenerative disorders.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12842-12844}, doi = {10.1073/pnas.1818493115}, pmid = {30504142}, issn = {1091-6490}, mesh = {*Amyotrophic Lateral Sclerosis ; Humans ; Mutation ; *Neurodegenerative Diseases ; Nonsense Mediated mRNA Decay ; }, } @article {pmid30504141, year = {2018}, author = {Du, X and de Almeida, P and Manieri, N and de Almeida Nagata, D and Wu, TD and Harden Bowles, K and Arumugam, V and Schartner, J and Cubas, R and Mittman, S and Javinal, V and Anderson, KR and Warming, S and Grogan, JL and Chiang, EY}, title = {CD226 regulates natural killer cell antitumor responses via phosphorylation-mediated inactivation of transcription factor FOXO1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11731-E11740}, doi = {10.1073/pnas.1814052115}, pmid = {30504141}, issn = {1091-6490}, abstract = {Natural killer (NK) cell recognition of tumor cells is mediated through activating receptors such as CD226, with suppression of effector functions often controlled by negative regulatory transcription factors such as FOXO1. Here we show that CD226 regulation of NK cell cytotoxicity is facilitated through inactivation of FOXO1. Gene-expression analysis of NK cells isolated from syngeneic tumors grown in wild-type or CD226-deficient mice revealed dysregulated expression of FOXO1-regulated genes in the absence of CD226. In vitro cytotoxicity and stimulation assays demonstrated that CD226 is required for optimal killing of tumor target cells, with engagement of its ligand CD155 resulting in phosphorylation of FOXO1. CD226 deficiency or anti-CD226 antibody blockade impaired cytotoxicity with concomitant compromised inactivation of FOXO1. Furthermore, inhibitors of FOXO1 phosphorylation abrogated CD226-mediated signaling and effector responses. These results define a pathway by which CD226 exerts control of NK cell responses against tumors.}, } @article {pmid30503950, year = {2019}, author = {Wang, M and Buček, A and Šobotník, J and Sillam-Dussès, D and Evans, TA and Roisin, Y and Lo, N and Bourguignon, T}, title = {Historical biogeography of the termite clade Rhinotermitinae (Blattodea: Isoptera).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {100-104}, doi = {10.1016/j.ympev.2018.11.005}, pmid = {30503950}, issn = {1095-9513}, abstract = {Termites are the principal decomposers in tropical and subtropical ecosystems around the world. Time-calibrated molecular phylogenies show that some lineages of Neoisoptera diversified during the Oligocene and Miocene, and acquired their pantropical distribution through transoceanic dispersal events, probably by rafting in wood. In this paper, we intend to resolve the historical biogeography of one of the earliest branching lineages of Neoisoptera, the Rhinotermitinae. We used the mitochondrial genomes of 27 species of Rhinotermitinae to build two robust time-calibrated phylogenetic trees that we used to reconstruct the ancestral distribution of the group. Our analyses support the monophyly of Rhinotermitinae and all genera of Rhinotermitinae. Our molecular clock trees provided time estimations that diverged by up to 15.6 million years depending on whether or not 3rd codon positions were included. Rhinotermitinae arose 50.4-64.6 Ma (41.7-74.5 Ma 95% HPD). We detected four disjunctions among biogeographic realms, the earliest of which occurred 41.0-56.6 Ma (33.0-65.8 Ma 95% HPD), and the latest of which occurred 20.3-34.2 Ma (15.9-40.4 Ma 95% HPD). These results show that the Rhinotermitinae acquired their distribution through a combination of transoceanic dispersals and dispersals across land bridges.}, } @article {pmid30503949, year = {2019}, author = {Tseng, YH and Monro, AK and Wei, YG and Hu, JM}, title = {Molecular phylogeny and morphology of Elatostema s.l. (Urticaceae): Implications for inter- and infrageneric classifications.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {251-264}, doi = {10.1016/j.ympev.2018.11.016}, pmid = {30503949}, issn = {1095-9513}, abstract = {Elatostema s.s. (Urticaceae) comprises approximately 500 species of herbs and subshrubs distributed in tropical and subtropical Asia, Australasia, and Africa. The delimitation of Elatostema s.s. and the closely related genera Elatostematoides, Pellionia, and Procris has long been problematic because of the large number of taxa and presumed homoplasy among diagnostic morphological characters. In the present study, we refer to these four genera together as Elatostema s.l. To evaluate the circumscription of Elatostema s.l. and its generic and subgeneric classification, we conducted phylogenetic analyses of DNA sequence data from the internal transcribed spacer of the nuclear genome (nrITS) and two markers from the plastid genome (psbA-trnH and psbM-trnD) for 126 taxa, representing 88 species of Elatostema s.s., four of Elatostematoides, nine of Pellionia, and five of Procris. Ten selected morphological characters were investigated using ancestral state reconstructions. Our results show that Elatostema s.l. can be divided into three well-supported and morphologically distinct genera: Procris, Elatostematoides, and Elatostema sensu auct. The results of our molecular phylogeny suggest four strongly supported clades within this newly defined Elatostema s.a.: core Elatostema, Pellionia, Weddellia, and an as yet undescribed clade African Elatostema. Homoplasy among the morphological characters used in this study makes it impossible to circumscribe genera using synapomorphies, but combined suites of characters do enable the morphological diagnosis of Elatostema s.a., Elatostematoides, and Procris.}, } @article {pmid30503875, year = {2018}, author = {Gore, J}, title = {Simple organizing principles in microbial communities.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {195-202}, doi = {10.1016/j.mib.2018.11.007}, pmid = {30503875}, issn = {1879-0364}, abstract = {There is a great deal of interest in discovering the principles that organize microbial communities, to better understand the structure and diversity of these communities in the natural world. Recent conceptual and technical advances have shown how simple organizing principles can give rise to surprising diversity and complex patterns in these consortia. Understanding competition, cooperation, and communication among microbes has provided novel insights into the structure and behavior of microbial collectives, and the use of simple animal models has advanced our understanding of microbial ecology in the host. These multidisciplinary efforts to understand and predict the properties of microbial communities will be critical in the development of microbial ecology as an applied science.}, } @article {pmid30503571, year = {2019}, author = {Trabucchi, M}, title = {Subcellular Heterogeneity of the microRNA Machinery.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {15-28}, doi = {10.1016/j.tig.2018.10.006}, pmid = {30503571}, issn = {0168-9525}, abstract = {Different methods have recently been developed to understand the subcellular localization and role of microRNAs (miRNAs) as well as small RNAs associated with Argonaute (AGO) proteins. The heterogeneity of the protein complexes associated with miRNAs, along with their subcellular localization, provides clues into their biochemical mechanism of function. Subcellular diversity indicates that miRNAs localized to different cellular regions could have different functions, including transcriptional regulation on chromatin or post-transcriptional control, providing global regulation of gene expression by miRNAs. Herein, I review the current knowledge and most recent discoveries relating to the subcellular function of miRNAs and other AGO-associated small RNAs, revealing the emergence of a multitude of functions of the miRNA pathway to control different steps of the gene expression program(s).}, } @article {pmid30503570, year = {2019}, author = {Zhang, X and Emerson, JJ}, title = {Inferring Compensatory Evolution of cis- and trans-Regulatory Variation.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {1-3}, doi = {10.1016/j.tig.2018.11.003}, pmid = {30503570}, issn = {0168-9525}, } @article {pmid30503569, year = {2018}, author = {Fišarová, L and Pantůček, R and Botka, T and Doškař, J}, title = {Variability of resistance plasmids in coagulase-negative staphylococci and their importance as a reservoir of antimicrobial resistance.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.11.004}, pmid = {30503569}, issn = {1769-7123}, abstract = {Coagulase-negative staphylococci (CoNS) are an important cause of human and animal diseases. Treatment of these diseases is complicated by their common antimicrobial resistance, caused by overuse of antibiotics in hospital and veterinary environment. Therefore, they are assumed to serve as a reservoir of resistance genes often located on plasmids. In this study, we analyzed plasmid content in 62 strains belonging to 10 CoNS species of human and veterinary origin. In 48 (77%) strains analyzed, 107 different plasmids were detected, and only some of them showed similarities with plasmids found previously. In total, seven different antimicrobial-resistance genes carried by plasmids were identified. Five of the CoNS staphylococci carried plasmids identical with either those of other CoNS species tested, or a well characterized Staphylococcus aureus strain COL, suggesting plasmid dissemination through horizontal transfer. To demonstrate the possibility of horizontal transfer, we performed electroporation of four resistance plasmids among Staphylococcus epidermidis, Staphylococcus petrasii, and coagulase-positive S. aureus strains. Plasmids were transferred unchanged, were stably maintained in recipient strains, and expressed resistance genes. Our work demonstrates a great variability of plasmids in human and veterinary staphylococcal strains and their ability to maintain and express resistance plasmids from other staphylococcal species.}, } @article {pmid30503365, year = {2019}, author = {Jenkins, TP and Brindley, PJ and Gasser, RB and Cantacessi, C}, title = {Helminth Microbiomes - A Hidden Treasure Trove?.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {13-22}, doi = {10.1016/j.pt.2018.10.007}, pmid = {30503365}, issn = {1471-5007}, abstract = {There is increasing attention on the complex interactions occurring between gastrointestinal parasitic helminths and the microbial flora (microbiota) inhabiting the host gut. However, little is known about the occurrence, structure, and function of microbial populations residing within parasite organs and tissues. In this article, we argue that an in-depth understanding of the interplay between parasites and their microbiomes may significantly enhance current knowledge of parasite biology and physiology, and may lead to the discovery of entirely novel, anthelmintic-independent interventions against parasites and parasitic diseases.}, } @article {pmid30502931, year = {2019}, author = {Trinh, JT and Zeng, L}, title = {Structure Regulates Phage Lysis-Lysogeny Decisions.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {3-4}, doi = {10.1016/j.tim.2018.11.005}, pmid = {30502931}, issn = {1878-4380}, support = {R01 GM107597/GM/NIGMS NIH HHS/United States ; }, abstract = {There are many strategies by which cell fates are decided. In one intriguing case, viruses communicate via the quorum-sensing-like 'arbitrium' system to bias infection outcomes. Through elucidating the detailed molecular mechanisms of such strategies, we can better understand viral propagation and offer insights into the treatment of viral diseases.}, } @article {pmid30502904, year = {2019}, author = {Aguilar-Camacho, JM and Doonan, L and McCormack, GP}, title = {Evolution of the main skeleton-forming genes in sponges (phylum Porifera) with special focus on the marine Haplosclerida (class Demospongiae).}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {245-253}, doi = {10.1016/j.ympev.2018.11.015}, pmid = {30502904}, issn = {1095-9513}, abstract = {The skeletons of sponges (Phylum Porifera) are comprised of collagen, often embedded with small siliceous structures (spicules) arranged in various forms to provide strength and flexibility. The main proteins responsible for the formation of the spicules in demosponges are the silicateins, which are related to the cathepsins L of other animals. While the silicatein active site, necessary for the formation of biosilica crystals, is characterized by the amino acids SHN, different variants of the silicatein genes have been found, some that retain SHN at the active site and some that don't. As part of an effort to further understand skeleton formation in marine sponges of the order Haplosclerida, a search for all silicatein variants were made in Irish species representing the main clades of this large sponge group. For this task, transcriptomes were sequenced and de novo assembled from Haliclona oculata, H. simulans and H. indistincta. Silicatein genes were identified from these and all available genomes and transcriptomes from Porifera. These were analysed along with all complete silicateins from GenBank. Silicateins were only found in species belonging to the class Demospongiae but excluding Keratosa and Verongimorpha and there was significant duplication and diversity of these genes. Silicateins showing SHN at the active site were polyphyletic. Indeed silicatein sequences were divided into six major clades (CHNI, CHNII, CHNIII, SHNI, SHNII and C/SQN). In those clades where haplosclerids were well represented the silicatein phylogeny reflected previous ribosomal and mitochondrial topologies. The most basal silicatein clade (CHNI) contained sequences only from marine haplosclerids and freshwater sponges while one silicatein from H. indistincta was more related to cathepsins L (outgroup) than to the overall silicatein clade indicating the presence of an old silicatein or an intermediary form. This data could suggest that marine haplosclerids were one of the first groups of extant demosponges to acquire silicatein genes. Furthermore, we suggest that the paucity of spicule types in this group may be due to their single copy of SHNI variants, and the lack of a silintaphin gene.}, } @article {pmid30502902, year = {2018}, author = {Plavcan, M and Alba, DM and Elton, S}, title = {Editorial announcement.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {A1}, doi = {10.1016/j.jhevol.2018.11.006}, pmid = {30502902}, issn = {1095-8606}, } @article {pmid30502901, year = {2018}, author = {Kamberov, YG and Guhan, SM and DeMarchis, A and Jiang, J and Wright, SS and Morgan, BA and Sabeti, PC and Tabin, CJ and Lieberman, DE}, title = {Comparative evidence for the independent evolution of hair and sweat gland traits in primates.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {99-105}, pmid = {30502901}, issn = {1095-8606}, support = {P51 RR000168/RR/NCRR NIH HHS/United States ; P51 RR000165/RR/NCRR NIH HHS/United States ; R01 HD032443/HD/NICHD NIH HHS/United States ; R21 AR066289/AR/NIAMS NIH HHS/United States ; DP2 OD006514/OD/NIH HHS/United States ; }, abstract = {Humans differ in many respects from other primates, but perhaps no derived human feature is more striking than our naked skin. Long purported to be adaptive, humans' unique external appearance is characterized by changes in both the patterning of hair follicles and eccrine sweat glands, producing decreased hair cover and increased sweat gland density. Despite the conspicuousness of these features and their potential evolutionary importance, there is a lack of clarity regarding how they evolved within the primate lineage. We thus collected and quantified the density of hair follicles and eccrine sweat glands from five regions of the skin in three species of primates: macaque, chimpanzee and human. Although human hair cover is greatly attenuated relative to that of our close relatives, we find that humans have a chimpanzee-like hair density that is significantly lower than that of macaques. In contrast, eccrine gland density is on average 10-fold higher in humans compared to chimpanzees and macaques, whose density is strikingly similar. Our findings suggest that a decrease in hair density in the ancestors of humans and apes was followed by an increase in eccrine gland density and a reduction in fur cover in humans. This work answers long-standing questions about the traits that make human skin unique and substantiates a model in which the evolution of expanded eccrine gland density was exclusive to the human lineage.}, } @article {pmid30502900, year = {2018}, author = {Dal Pesco, F and Fischer, J}, title = {Greetings in male Guinea baboons and the function of rituals in complex social groups.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {87-98}, doi = {10.1016/j.jhevol.2018.10.007}, pmid = {30502900}, issn = {1095-8606}, abstract = {Ritualized greetings, defined as exchanges of non-aggressive signals, are common among males living in multi-male groups and are thought to balance the trade-offs of male co-residence. While ritualized greetings are widespread in the animal kingdom, the behavioral repertoire described in the genus Papio is exceptional, as it involves potentially harmful behaviors such as genital fondling. Although greetings are one of the most striking male social interactions in baboons, their function is still disputed. We investigated the function of male-male ritualized greeting behavior in wild Guinea baboons. This species lives in multilevel societies where several 'units' comprising a primary male, females with young, and occasionally a secondary male form a 'party', and two to three parties form a gang. Adult males maintain affiliative relationships with preferred male partners whom they support in coalitions, regardless of kinship. We examined the social behavior of 24 adolescent and adult males (∼900 h focal observations) in the Niokolo-Koba National Park, Senegal, to test whether greetings reflect relationship quality or function to buffer tension. Greetings were ten times more frequent than aggression and twice as frequent as affiliation. Neither dyadic aggression nor tense context predicted greeting rate, discounting the buffering hypothesis. Greetings occurred almost exclusively between males of the same party, even when other parties were around. Within parties, spatially tolerant partners greeted more frequently but dyads did not greet due to proximity prior to the greeting. Although affiliation did not predict overall greeting rate, intense and potentially costly greetings were more likely between males with stronger affiliative relationships. Greetings in Guinea baboons appear to signal commitment among party members, test relationships among spatially tolerant partners, and accentuate relationship strength among highly affiliated males. Although ritualized baboon greetings lack the symbolic component of human rituals, they appear to serve similar functions, specifically to strengthen in-group affiliation and promote cooperation.}, } @article {pmid30502899, year = {2018}, author = {d'Errico, F and Doyon, L and Zhang, S and Baumann, M and Lázničková-Galetová, M and Gao, X and Chen, F and Zhang, Y}, title = {The origin and evolution of sewing technologies in Eurasia and North America.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {71-86}, doi = {10.1016/j.jhevol.2018.10.004}, pmid = {30502899}, issn = {1095-8606}, abstract = {When, how, and following which paths hominins created the innovations that allowed them to colonize regions of the planet that were not suited to their thermal physiology is still a matter of inquiry. In this paper, we elaborate a theoretical framework to investigate the origin and diversification of bone needles, summarize the evidence for their emergence, create a large database of their morphometric and stylistic characters, and present results of the study of an exceptionally well-preserved collection of needles from Shuidonggou Locality 12 (SDG12), a site located in the Ningxia Hui Autonomous Region, Northern China, dated to ca. 11.2 ka BP. Bone needles are reported from 271 sites and 355 archaeological layers. Revision of the evidence shows they represent an original cultural innovation that emerged in Eurasia between 45-40 ka BP. Size differences between the earliest known specimens, found in Siberia and China, indicate needles may have been invented independently in these two regions. Needles from Eastern Europe may represent either an independent invention or a geographic extension of earlier Siberian and Caucasian sewing traditions. In Western Europe, needles appear during the Solutrean. The wider size range characteristic of Magdalenian specimens supports the idea that needles of different sizes were used in a variety of tasks. In China, the robust sub-circular needles found at sites dated between 35-25 ka BP are followed, between 26-23 ka BP, by small flat needles, which may represent an innovation associated with the microblades/microcores toolkit. At SDG12, technological, functional, and morphometric analyses of finished needles and manufacturing by-products identify two previously undetected reduction sequences for the production of needles of different size and, probably, function. The bone needles found at Paleoindian sites are the smallest and reflect a never previously achieved mastery in the production of such tools.}, } @article {pmid30502898, year = {2018}, author = {Kealy, S and Louys, J and O'Connor, S}, title = {Least-cost pathway models indicate northern human dispersal from Sunda to Sahul.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {59-70}, doi = {10.1016/j.jhevol.2018.10.003}, pmid = {30502898}, issn = {1095-8606}, abstract = {Archaeological records from Australia provide the earliest, indirect evidence for maritime crossings by early modern humans, as the islands to the north-west of the continent (Wallacea) have never been connected to the mainland. Suggested in 1977 by Joseph B. Birdsell, the two main routes from Sunda (mainland Southeast Asia) to Sahul (Australia-New Guinea), still in debate today, are a northern route through Sulawesi with a landing in New Guinea, or a southern route through Bali, Timor and thence landing in northern Australia. Here we construct least-cost pathway models of human dispersal from Sunda to Sahul at 65 ka and 70 ka by extending previous out-of-Africa least-cost models through the digitization of these routes. We recover overwhelming support for a northern route into Sahul, with a landing location on present-day Misool Island. Minimal support is also recovered for the southern route at 70 ka, with a possible crossing to Sahul from eastern Timor. Review of archaeological records on the Wallacean islands crossed by our northern route indicate a dearth of archaeological research in this region. Meanwhile, the comparatively better studied southern islands still lack any archaeological dates comparable to those known for initial occupation in Sunda and Sahul. Based on our model results we suggest Misool Island as the initial landing site for early modern humans on Sahul and recommend a future focus on archaeological fieldwork in the northern Wallacean islands.}, } @article {pmid30502897, year = {2018}, author = {Rossie, JB and Hill, A}, title = {A new species of Simiolus from the middle Miocene of the Tugen Hills, Kenya.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {50-58}, doi = {10.1016/j.jhevol.2018.09.002}, pmid = {30502897}, issn = {1095-8606}, abstract = {A new species of the "small-bodied ape" Simiolus is described here that extends the temporal range of the genus to the end of the Middle Miocene. As such, it is one of the few species of fossil primates known from East Africa during a time of significant change in which Old World monkeys and crown hominoids replaced the primitive ape-like primates that had dominated the early Miocene. The dynamics of this important event in our evolutionary history are obscured by the small number of fossil primates known from Africa between 14 and 6 million years ago, as well as persistent ambiguity regarding the phylogenetic status of the ape-like Miocene primates. The new species described here helps to fill this temporal gap, and our analysis of its phylogenetic position suggests that Simiolus and many other Miocene primates were not only ape-like, they were, indeed, stem hominoids. Judging from the available material, the new species may be the smallest known ape.}, } @article {pmid30502896, year = {2018}, author = {van Noordwijk, MA and Utami Atmoko, SS and Knott, CD and Kuze, N and Morrogh-Bernard, HC and Oram, F and Schuppli, C and van Schaik, CP and Willems, EP}, title = {The slow ape: High infant survival and long interbirth intervals in wild orangutans.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {38-49}, doi = {10.1016/j.jhevol.2018.09.004}, pmid = {30502896}, issn = {1095-8606}, abstract = {Orangutans (Pongo spp.) are reported to have extremely slow life histories, including the longest average interbirth intervals of all mammals. Such slow life history can be viable only when unavoidable mortality is kept low. Thus, orangutans' survivorship under natural conditions is expected to be extremely high. Previous estimates of orangutan life history were based on captive individuals living under very different circumstances or on small samples from wild populations. Here, we combine birth data from seven field sites, each with demographic data collection for at least 10 years (range 12-43 years) on wild orangutans to better document their life history. Using strict criteria for data inclusion, we calculated infant survival, interbirth intervals and female age at first reproduction, across species, subspecies and islands. We found an average closed interbirth interval of 7.6 years, as well as consistently very high pre-weaning survival for males and females. Female survival of 94% until age at first birth (at around age 15 years) was higher than reported for any other mammal species under natural conditions. Similarly, annual survival among parous females is very high, but longevity remains to be estimated. Current data suggest no major life history differences between Sumatran and Bornean orangutans. The high offspring survival is remarkable, noting that modern human populations seem to have reached the same level of survival only in the 20th century. The orangutans' slow life history illustrates what can be achieved if a hominoid bauplan is exposed to low unavoidable mortality. Their high survival is likely due to their arboreal and non-gregarious lifestyle, and has allowed them to maintain viable populations, despite living in low-productivity habitats. However, their slow life history also implies that orangutans are highly vulnerable to a catastrophic population crash in the face of drastic habitat change.}, } @article {pmid30502895, year = {2018}, author = {Thompson, NE and O'Neill, MC and Holowka, NB and Demes, B}, title = {Step width and frontal plane trunk motion in bipedal chimpanzee and human walking.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {27-37}, doi = {10.1016/j.jhevol.2018.09.006}, pmid = {30502895}, issn = {1095-8606}, abstract = {Human bipedalism is characterized by mediolateral oscillations of the center of mass (CoM) between the feet. The preferred step widths and CoM oscillations used by humans likely represent a trade-off of several factors (e.g., stance and swing phase costs). However, it is difficult to assess whether human frontal plane control strategies are unique given few detailed data on frontal plane motion during facultative bipedalism in apes. Here, we collected three-dimensional kinematic and kinetic data in humans and chimpanzees to investigate the relationship between step width, mediolateral CoM motion, frontal plane trunk kinematics, and CoM power during bipedalism. Chimpanzee bipedalism entails mediolateral CoM oscillations and step widths that are (scaled to lower/hind limb length) three times larger than those of humans. Chimpanzees use a combination of linear and angular motion of the trunk and list the entire trunk, and especially thorax, over the stance side foot, generating large mediolateral shifts in the CoM, whereas humans utilize little angular motion within the trunk. Larger mediolateral CoM motions do not have a significant effect on CoM power. Similarities between bipedal chimpanzees and other bipedal non-human primates (macaques and gibbons) indicate that narrow CoM motions are unique to humans and are likely due to our adducted hips and valgus knees. Valgus knees appear early in the human fossil record (∼3.6 Ma), contemporaneous with the Laetoli footprints. However, fossils attributed to Ardipithecus ramidus (∼4.4 Ma) suggest that the earliest hominins may have lacked a hominin-like degree of knee valgus. If correct, this suggests that this species may have used wide steps, larger mediolateral CoM motions, and perhaps larger trunk motions during bipedal walking. Finally, we present a novel means to estimate mediolateral CoM motion from trackway step width, and estimate that the Laetoli G track maker used CoM motions within the human range.}, } @article {pmid30502894, year = {2018}, author = {Ogihara, N and Hirasaki, E and Andrada, E and Blickhan, R}, title = {Bipedal gait versatility in the Japanese macaque (Macaca fuscata).}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {2-14}, doi = {10.1016/j.jhevol.2018.09.001}, pmid = {30502894}, issn = {1095-8606}, abstract = {It was previously believed that, among primates, only humans run bipedally. However, there is now growing evidence that at least some non-human primates can not only run bipedally but can also generate a running gait with an aerial phase. Japanese macaques trained for bipedal performances have been known to exhibit remarkable bipedal locomotion capabilities, but no aerial-phase running has previously been reported. In the present study, we investigated whether Japanese macaques could run with an aerial phase by collecting bipedal gait sequences from three macaques on a level surface at self-selected speeds (n = 188). During our experiments, body kinematics and ground reaction forces were recorded by a motion-capture system and two force plates installed within a wooden walkway. Our results demonstrated that macaques were able to utilize a variety of bipedal gaits including grounded running, skipping, and even running with an aerial phase. The self-selected bipedal locomotion speed of the macaques was fast, with Froude speed ranging from 0.4 to 1.3. However, based on congruity, no single trial that could be categorized as a pendulum-like walking gait was observed. The parameters describing the temporal, kinematic, and dynamic characteristics of macaque bipedal running gaits follow the patterns previously documented for other non-human primates and terrestrial birds that use running gaits, but are different from those of humans and from birds' walking gaits. The present study confirmed that when a Japanese macaque engages in bipedal locomotion, even without an aerial phase, it generally utilizes a spring-like running mechanism because the animals have a limited ability to stiffen their legs. That limitation is due to anatomical restrictions determined by the morphology and structure of the macaque musculoskeletal system. The general adoption of grounded running in macaques and other non-human primates, along with its absence in human bipedal locomotion, suggests that abandonment of compliant gait was a critical transition in the evolution of human obligatory bipedalism.}, } @article {pmid30502893, year = {2018}, author = {Green, DJ and Chirchir, H and Mbua, E and Harris, JWK and Braun, DR and Griffin, NL and Richmond, BG}, title = {Scapular anatomy of Paranthropus boisei from Ileret, Kenya.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {181-192}, doi = {10.1016/j.jhevol.2017.06.013}, pmid = {30502893}, issn = {1095-8606}, abstract = {KNM-ER 47000A is a new 1.52 Ma hominin scapular fossil belonging to an associated partial skeleton from the Koobi Fora Formation, Kenya (FwJj14E, Area 1A). This fossil effectively doubles the record of Early Pleistocene scapulae from East Africa, with KNM-WT 15000 (early African Homo erectus) preserving the only other known scapula to date. KNM-ER 47000A consists of a complete glenoid cavity preserving a portion of the scapular spine and neck, the proximal half of the acromion, and a majority of the axillary border. A sufficient amount of anatomy is preserved to compare KNM-ER 47000A with scapulae of several Australopithecus species, extinct Homo, and living hominoids. The glenohumeral joint of KNM-ER 47000A is more laterally oriented than those of great apes and Australopithecus, aligning it closely with KNM-WT 15000 and modern humans. While this morphology does not imply a strong commitment to arboreality, its scapular spine is obliquely oriented-as in gorillas and some Australopithecus fossils-particularly when compared to the more horizontal orientation seen in KNM-WT 15000 and modern humans. Such a spine orientation suggests a narrow yet long infraspinous region, a feature that has been attributed to suspensory taxa. Accordingly, the morphology of KNM-ER 47000A presents conflicting behavioral implications. Nonetheless, a multivariate consideration of the available scapular traits aligns KNM-ER 47000A and Australopithecus with great apes, whereas KNM-WT 15000 resembles modern humans. The scapular morphology of KNM-ER 47000A is unique among fossil and extant hominoids and its morphological differences from KNM-WT 15000 strengthen the attribution of KNM-ER 47000 to Paranthropus boisei as opposed to early Homo. As the first evidence of scapular morphology in P. boisei, KNM-ER 47000A provides important new information on variation in hominin shoulder and upper limb anatomy from this critical period of hominin evolutionary history.}, } @article {pmid30502892, year = {2018}, author = {Thompson, NE and Rubinstein, D and Larson, SG}, title = {Great ape thorax and shoulder configuration-An adaptation for arboreality or knuckle-walking?.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {15-26}, doi = {10.1016/j.jhevol.2018.09.005}, pmid = {30502892}, issn = {1095-8606}, abstract = {Great apes exhibit a suite of morphological traits of the shoulder and upper thorax that have traditionally been linked to orthograde arborealism. Recently it has been proposed that these traits are instead adaptations for knuckle-walking, and more broadly, that knuckle-walking itself is an adaptation for shock absorption during terrestriality. Here we test several tenets of these hypotheses using kinematic and kinetic data from chimpanzees and macaques, and electromyographic data of shoulder muscle activity in chimpanzees. We collected 3D kinematic data to quantify motion of the acromion and trunk during quadrupedalism and vertical climbing in chimpanzees as well as ground reaction forces to investigate the presence and magnitude of impact transient forces during terrestrial locomotion in chimpanzees and macaques. We also investigated patterns of recruitment of select forelimb musculature (triceps brachii and serratus anterior) using previously collected data in chimpanzees to determine whether these muscles may function to absorb impact transient forces. We found that the acromion is significantly more elevated in vertical climbing than during knuckle-walking, while dorsoventral ranges and magnitudes of motion were similar between gaits. Ground reaction forces indicate that only a minority of strides in either chimpanzees or macaques have transient forces and, when present, these transient forces as well as loading rates are small. Electromyographic results show that activity of the triceps brachii may facilitate energy absorption while serratus anterior likely functions to support the trunk, as in other primates. Our data suggest there is little to no evidence supporting recent hypotheses that the African ape upper thorax and shoulder configuration is an adaptation for knuckle-walking, or more broadly, that knuckle-walking exists as an adaptation to absorb impact shock during terrestriality. We do however find some evidence that shoulder configuration allows greater scapular elevation in chimpanzees during arboreal behaviors (e.g., vertical climbing).}, } @article {pmid30502891, year = {2018}, author = {Bardo, A and Vigouroux, L and Kivell, TL and Pouydebat, E}, title = {The impact of hand proportions on tool grip abilities in humans, great apes and fossil hominins: A biomechanical analysis using musculoskeletal simulation.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {106-121}, doi = {10.1016/j.jhevol.2018.10.001}, pmid = {30502891}, issn = {1095-8606}, abstract = {Differences in grip techniques used across primates are usually attributed to variation in thumb-finger proportions and muscular anatomy of the hand. However, this cause-effect relationship is not fully understood because little is known about the biomechanical functioning and mechanical loads (e.g., muscle or joint forces) of the non-human primate hand compared to that of humans during object manipulation. This study aims to understand the importance of hand proportions on the use of different grip strategies used by humans, extant great apes (bonobos, gorillas and orangutans) and, potentially, fossil hominins (Homo naledi and Australopithecus sediba) using a musculoskeletal model of the hand. Results show that certain grips are more challenging for some species, particularly orangutans, than others, such that they require stronger muscle forces for a given range of motion. Assuming a human-like range of motion at each hand joint, simulation results show that H. naledi and A. sediba had the biomechanical potential to use the grip techniques considered important for stone tool-related behaviors in humans. These musculoskeletal simulation results shed light on the functional consequences of the different hand proportions among extant and extinct hominids and the different manipulative abilities found in humans and great apes.}, } @article {pmid30502890, year = {2018}, author = {Kirk, EC and Williams, BA}, title = {Corrigendum to "New adapiform primate of Old World affinities from the Devil's Graveyard Formation of Texas" [J Hum Evol 61 (2011) 156-168].}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {1}, doi = {10.1016/j.jhevol.2018.08.008}, pmid = {30502890}, issn = {1095-8606}, } @article {pmid30502720, year = {2018}, author = {Yang, C and Ottemann, KM}, title = {Control of bacterial colonization in the glands and crypts.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {38-44}, doi = {10.1016/j.mib.2018.11.004}, pmid = {30502720}, issn = {1879-0364}, abstract = {The epithelial cell layer of the major organs of the mammalian gastrointestinal (GI) tract is extensively invaginated into thousands of gland and crypt structures. These are lined by distinct sets of epithelial cells and may comprise discrete niches. The host maximizes the distance between the epithelial cell layer and GI-inhabiting microbes to limit inflammation, and these strategies also likely keep bacteria out of the glands and crypts. We discuss here the specific host processes that have been shown to restrict bacterial presence in the glands and crypts, specifically the immune system, acid, mucin, oxygen, and reactive oxygen species. Not surprisingly, microbes have evolved sophisticated strategies to overcome these host factors and reside close to the epithelium in the glands and crypts. Bacterial properties important for gland and crypt colonization include bacterial immunomodulatory molecules, chemotaxis, and the use of certain metabolites. Overall, these as-yet limited studies suggest there are specific host and bacterial properties that control gland and crypt colonization, contributing to the overall microbial spatial organization of the GI tract. However, there remains much to be discovered in this area.}, } @article {pmid30502396, year = {2019}, author = {Fassio, G and Modica, MV and Alvaro, MC and Buge, B and Salvi, D and Oliverio, M and Schiaparelli, S}, title = {An Antarctic flock under the Thorson's rule: Diversity and larval development of Antarctic Velutinidae (Mollusca: Gastropoda).}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {1-13}, doi = {10.1016/j.ympev.2018.11.017}, pmid = {30502396}, issn = {1095-9513}, abstract = {In most marine gastropods, the duration of the larval phase is a key feature, strongly influencing species distribution and persistence. Antarctic lineages, in agreement with Thorson's rule, generally show a short pelagic developmental phase (or lack it completely), with very few exceptions. Among them is the ascidian-feeding gastropod family Velutinidae, a quite understudied group. Based on a multilocus (COI, 16S, 28S and ITS2) dataset for 182 specimens collected in Antarctica and other regions worldwide, we investigated the actual Antarctic velutinid diversity, inferred their larval development, tested species genetic connectivity and produced a first phylogenetic framework of the family. We identified 15 Antarctic Molecular Operational Taxonomic Units (MOTUs), some of which represented undescribed species, which show two different types of larval shell, indicating different duration of the Pelagic Larval Phase (PLD). Antarctic velutinids stand as an independent lineage, sister to the rest of the family, with extensive hidden diversity likely produced by rapid radiation. Our phylogenetic framework indicates that this Antarctic flock underwent repeated events of pelagic phase shortening, in agreement with Thorson's rule, yielding species with restricted geographic ranges.}, } @article {pmid30502325, year = {2019}, author = {Oonuma, K and Kusakabe, TG}, title = {Spatio-temporal regulation of Rx and mitotic patterns shape the eye-cup of the photoreceptor cells in Ciona.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {245-255}, doi = {10.1016/j.ydbio.2018.11.011}, pmid = {30502325}, issn = {1095-564X}, abstract = {The ascidian larva has a pigmented ocellus comprised of a cup-shaped array of approximately 30 photoreceptor cells, a pigment cell, and three lens cells. Morphological, physiological and molecular evidence has suggested evolutionary kinship between the ascidian larval photoreceptors and vertebrate retinal and/or pineal photoreceptors. Rx, an essential factor for vertebrate photoreceptor development, has also been suggested to be involved in the development of the ascidian photoreceptor cells, but a recent revision of the photoreceptor cell lineage raised a crucial discrepancy between the reported expression patterns of Rx and the cell lineage. Here, we report spatio-temporal expression patterns of Rx at single-cell resolution along with mitotic patterns up to the final division of the photoreceptor-lineage cells in Ciona. The expression of Rx commences in non-photoreceptor a-lineage cells on the right side of the anterior sensory vesicle at the early tailbud stage. At the mid tailbud stage, Rx begins to be expressed in the A-lineage photoreceptor cell progenitors located on the right side of the posterior sensory vesicle. Thus, Rx is specifically but not exclusively expressed in the photoreceptor-lineage cells in the ascidian embryo. Two cis-regulatory modules are shown to be important for the photoreceptor-lineage expression of Rx. The cell division patterns of the photoreceptor-lineage cells rationally explain the generation of the cup-shaped structure of the pigmented ocellus. The present findings demonstrate the complete cell lineage of the ocellus photoreceptor cells and provide a framework elucidating the molecular and cellular mechanisms of photoreceptor development in Ciona.}, } @article {pmid30517755, year = {2018}, author = {Armando Gagliardi, P and Primo, L}, title = {Irreversible activation of Rho-activated kinases resulted from evolution of proteolytic sites within disordered regions in coiled-coil domain.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy229}, pmid = {30517755}, issn = {1537-1719}, abstract = {Activation of Rho-associated protein kinase 1 (ROCK1) and myotonic dystrophy kinase-related CDC42-binding kinase alpha (MRCKα) by caspases during apoptosis in vertebrates represents a prototypical example of co-option of kinases by proteases. How caspases acquired the ability to control these proteins during evolution of vertebrates is still unknown. Here, we report a phylogenetic and molecular study on the acquisition of caspase-cleavage sites in the family of Rho-activated kinases (RaKs). We demonstrate that the acquisition of such sites has more frequently occurred in identifiable intrinsically disordered regions (IDRs) within or flanking the coiled-coil domain. Thanks to computational identification of IDRs in protein sequences of different organisms, we predicted and validated the independent evolution of two caspase-cleavage sites in ROCK of arthropods and the loss of one of the MRCKα caspase-cleavage sites in ray-finned fishes. In conclusion, we shed light on the propensity of RaKs to evolve novel proteolytic sites, causing kinase activation and uniform subcellular distribution.}, } @article {pmid30517749, year = {2018}, author = {Inoue, J and Satoh, N}, title = {ORTHOSCOPE: an automatic web tool for phylogenetically inferring bilaterian orthogroups with user-selected taxa.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy226}, pmid = {30517749}, issn = {1537-1719}, abstract = {Identification of orthologous or paralogous relationships of coding genes is fundamental to all aspects of comparative genomics. For accurate identification of orthologs among deeply diversified bilaterian lineages, precise estimation of gene trees is indispensable, given the complicated histories of genes over millions of years. By estimating gene trees, orthologs can be identified as members of an orthogroup, a set of genes descended from a single gene in the last common ancestor of all the species being considered. In addition to comparisons with a given species tree, purposeful taxonomic sampling increases the accuracy of gene tree estimation and orthogroup identification. Although some major phylogenetic relationships of bilaterians are gradually being unraveled, the scattering of published genomic data among separate web databases is becoming a significant hindrance to identification of orthogroups with appropriate taxonomic sampling. By integrating more than 250 metazoan gene models predicted in genome projects, we developed a web tool called ORTHOSCOPE to identify orthogroups of specific protein-coding genes within major bilaterian lineages. ORTHOSCOPE allows users to employ several sequences of a specific molecule and broadly accepted nodes included in a user-specified species tree as queries and to evaluate the reliability of estimated orthogroups based on topologies and node support values of estimated gene trees. A test analysis using data from 36 bilaterians was accomplished within 140 seconds. ORTHOSCOPE results can be used to evaluate orthologs identified by other stand-alone programs using genome-scale data. ORTHOSCOPE is freely available at http://orthoscope.jp or https://github.com/jun-inoue/orthoscope (last accessed 14 November 2018).}, } @article {pmid30517748, year = {2018}, author = {Rogers, RL and Zhou, L and Chu, C and Márquez, R and Corl, A and Linderoth, T and Freeborn, L and MacManes, MD and Xiong, Z and Zheng, J and Guo, C and Xun, X and Kronforst, MR and Summers, K and Wu, Y and Yang, H and Richards-Zawacki, CL and Zhang, G and Nielsen, R}, title = {Genomic Takeover by Transposable Elements in the Strawberry Poison Frog.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2913-2927}, pmid = {30517748}, issn = {1537-1719}, abstract = {We sequenced the genome of the strawberry poison frog, Oophaga pumilio, at a depth of 127.5× using variable insert size libraries. The total genome size is estimated to be 6.76 Gb, of which 4.76 Gb are from high copy number repetitive elements with low differentiation across copies. These repeats encompass DNA transposons, RNA transposons, and LTR retrotransposons, including at least 0.4 and 1.0 Gb of Mariner/Tc1 and Gypsy elements, respectively. Expression data indicate high levels of gypsy and Mariner/Tc1 expression in ova of O. pumilio compared with Xenopus laevis. We further observe phylogenetic evidence for horizontal transfer (HT) of Mariner elements, possibly between fish and frogs. The elements affected by HT are present in high copy number and are highly expressed, suggesting ongoing proliferation after HT. Our results suggest that the large amphibian genome sizes, at least partially, can be explained by a process of repeated invasion of new transposable elements that are not yet suppressed in the germline. We also find changes in the spliceosome that we hypothesize are related to permissiveness of O. pumilio to increases in intron length due to transposon proliferation. Finally, we identify the complement of ion channels in the first genomic sequenced poison frog and discuss its relation to the evolution of autoresistance to toxins sequestered in the skin.}, } @article {pmid30517740, year = {2018}, author = {Petrov, AS and Wood, EC and Bernier, CR and Norris, AM and Brown, A and Amunts, A}, title = {Structural Patching Fosters Divergence of Mitochondrial Ribosomes.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy221}, pmid = {30517740}, issn = {1537-1719}, abstract = {Mitochondrial ribosomes (mitoribosomes) are essential components of all mitochondria that synthesize proteins encoded by the mitochondrial genome. Unlike other ribosomes, mitoribosomes are highly variable across species. The basis for this diversity is not known. Here, we examine the composition and evolutionary history of mitoribosomes across the phylogenetic tree by combining three-dimensional structural information with a comparative analysis of the secondary structures of mitochondrial rRNAs (mt-rRNAs) and available proteomic data. We generate a map of the acquisition of structural variation and reconstruct the fundamental stages that shaped the evolution of the mitoribosomal large subunit and led to this diversity. Our analysis suggests a critical role for ablation and expansion of rapidly evolving mt-rRNA. These changes cause structural instabilities that are "patched" by the acquisition of pre-existing compensatory elements, thus providing opportunities for rapid evolution. This mechanism underlies the incorporation of mt-tRNA into the central protuberance of the mammalian mitoribosome, and the altered path of the polypeptide exit tunnel of the yeast mitoribosome. We propose that since the toolkits of elements utilized for structural patching differ between mitochondria of different species, it fosters the growing divergence of mitoribosomes.}, } @article {pmid30517738, year = {2018}, author = {Ehrlich, F and Fischer, H and Langbein, L and Praetzel-Wunder, S and Ebner, B and Figlak, K and Weissenbacher, A and Sipos, W and Tschachler, E and Eckhart, L}, title = {Differential evolution of the epidermal keratin cytoskeleton in terrestrial and aquatic mammals.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy214}, pmid = {30517738}, issn = {1537-1719}, abstract = {Keratins are the main intermediate filament proteins of epithelial cells. In keratinocytes of the mammalian epidermis they form a cytoskeleton that resists mechanical stress and thereby are essential for the function of the skin as a barrier against the environment. Here, we performed a comparative genomics study of epidermal keratin genes in terrestrial and fully aquatic mammals to determine adaptations of the epidermal keratin cytoskeleton to different environments. We show that keratins K5 and K14 of the innermost (basal), proliferation-competent layer of the epidermis are conserved in all mammals investigated. By contrast, K1 and K10, which form the main part of the cytoskeleton in the outer (suprabasal) layers of the epidermis of terrestrial mammals, have been lost in whales and dolphins (cetaceans) and in the manatee. While in terrestrial mammalian epidermis K6 and K17 are expressed only upon stress-induced epidermal thickening, high levels of K6 and K17 are consistently present in dolphin skin, indicating constitutive expression and substitution of K1 and K10. K2 and K9, which are expressed in a body site-restricted manner in human and mouse suprabasal epidermis, have been lost in cetaceans and manatee but also in some terrestrial mammals. The evolution of alternative splicing of K10 and differentiation-dependent upregulation of K23 have increased the complexity of keratin expression in the epidermis of terrestrial mammals. Taken together, these results reveal evolutionary diversification of the epidermal cytoskeleton in mammals and suggest a complete replacement of the quantitatively predominant epidermal proteins of terrestrial mammals by originally stress-inducible keratins in cetaceans.}, } @article {pmid30517696, year = {2018}, author = {Ilhan, J and Kupczok, A and Woehle, C and Wein, T and Hülter, NF and Rosenstiel, P and Landan, G and Mizrahi, I and Dagan, T}, title = {Segregational drift and the interplay between plasmid copy number and evolvability.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy225}, pmid = {30517696}, issn = {1537-1719}, abstract = {The ubiquity of plasmids in all prokaryotic phyla and habitats and their ability to transfer between cells marks them as prominent constituents of prokaryotic genomes. Many plasmids are found in their host cell in multiple copies. This leads to an increased mutational supply of plasmid-encoded genes and genetically heterogeneous plasmid genomes. Nonetheless, the segregation of plasmid copies into daughter cells during cell division is considered to occur in the absence of selection on the plasmid alleles. We investigate the implications of random genetic drift of multicopy plasmids during cell division - termed here segregational drift - to plasmid evolution. Performing experimental evolution of low- and high-copy non-mobile plasmids in Escherichia coli, we find that the evolutionary rate of multicopy plasmids does not reflect the increased mutational supply expected according to their copy number. In addition, simulated evolution of multicopy plasmid alleles demonstrates that segregational drift leads to increased loss frequency and extended fixation time of plasmid mutations in comparison to haploid chromosomes. Furthermore, an examination of the experimentally evolved hosts reveals a significant impact of the plasmid type on the host chromosome evolution. Our study demonstrates that segregational drift of multicopy plasmids interferes with the retention and fixation of novel plasmid variants. Depending on the selection pressure on newly emerging variants, plasmid genomes may evolve slower than haploid chromosomes, regardless of their higher mutational supply. We suggest that plasmid copy number is an important determinant of plasmid evolvability due to the manifestation of segregational drift.}, } @article {pmid30517680, year = {2018}, author = {Haller, BC and Messer, PW}, title = {SLiM 3: Forward genetic simulations beyond the Wright-Fisher model.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy228}, pmid = {30517680}, issn = {1537-1719}, abstract = {With the desire to model population genetic processes under increasingly realistic scenarios, forward genetic simulations have become a critical part of the toolbox of modern evolutionary biology. The SLiM forward genetic simulation framework is one of the most powerful and widely used tools in this area. However, its foundation in the Wright-Fisher model has been found to pose an obstacle to implementing many types of models; it is difficult to adapt the Wright-Fisher model, with its many assumptions, to modeling ecologically realistic scenarios such as explicit space, overlapping generations, individual variation in reproduction, density-dependent population regulation, individual variation in dispersal or migration, local extinction and recolonization, mating between subpopulations, age structure, fitness-based survival and hard selection, emergent sex ratios, and so forth. In response to this need, we here introduce SLiM 3, which contains two key advancements aimed at abolishing these limitations. First, the new non-Wright-Fisher or "nonWF" model type provides a much more flexible foundation that allows the easy implementation of all of the above scenarios and many more. Second, SLiM 3 adds support for continuous space, including spatial interactions and spatial maps of environmental variables. We provide a conceptual overview of these new features, and present several example models to illustrate their use.}, } @article {pmid30517664, year = {2018}, author = {Flagel, L and Brandvain, Y and Schrider, DR}, title = {The Unreasonable Effectiveness of Convolutional Neural Networks in Population Genetic Inference.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy224}, pmid = {30517664}, issn = {1537-1719}, support = {R00 HG008696/HG/NHGRI NIH HHS/United States ; }, abstract = {Population-scale genomic datasets have given researchers incredible amounts of information from which to infer evolutionary histories. Concomitant with this flood of data, theoretical and methodological advances have sought to extract information from genomic sequences to infer demographic events such as population size changes and gene flow among closely related populations/species, construct recombination maps, and uncover loci underlying recent adaptation. To date most methods make use of only one or a few summaries of the input sequences and therefore ignore potentially useful information encoded in the data. The most sophisticated of these approaches involve likelihood calculations, which require theoretical advances for each new problem, and often focus on a single aspect of the data (e.g. only allele frequency information) in the interest of mathematical and computational tractability. Directly interrogating the entirety of the input sequence data in a likelihood-free manner would thus offer a fruitful alternative. Here we accomplish this by representing DNA sequence alignments as images and using a class of deep learning methods called convolutional neural networks (CNNs) to make population genetic inferences from these images. We apply CNNs to a number of evolutionary questions and find that they frequently match or exceed the accuracy of current methods. Importantly, we show that CNNs perform accurate evolutionary model selection and parameter estimation, even on problems that have not received detailed theoretical treatments. Thus, when applied to population genetic alignments, CNN are capable of outperforming expert-derived statistical methods, and offer a new path forward in cases where no likelihood approach exists.}, } @article {pmid30516463, year = {2018}, author = {Zhao, B and Hu, Q and Guo, X and Liao, Z and Bowers, KJ and Sarmiento, F and Mesbah, NM and Yan, Y and Li, J and Wiegel, J}, title = {Corrigendum: Natronolimnobius aegyptiacus sp. nov., an extremely halophilic alkalithermophilic archaeon isolated from the athalassohaline Wadi An Natrun, Egypt.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3954}, doi = {10.1099/ijsem.0.003118}, pmid = {30516463}, issn = {1466-5034}, } @article {pmid30516460, year = {2018}, author = {Baek, K and Choi, A and Lee, YM and Lee, HK and Cho, JC}, title = {Leucothrix arctica sp. nov., isolated from Arctic seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3851-3855}, doi = {10.1099/ijsem.0.003072}, pmid = {30516460}, issn = {1466-5034}, mesh = {Arctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Thiotrichaceae/*classification/genetics ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, non-motile, oxidase- and catalase-positive, rod-shaped bacterium was isolated from a coastal seawater sample from the Arctic Circle and designated strain IMCC9719T. On the basis of 16S rRNA gene sequence analysis, it was shown that strain IMCC9719T belonged to the genus Leucothrix and was closely related to the type strains of Leucothrix pacifica (97.6 % similarity) and Leucothrix mucor (95.1 %), while the strain shared <90.6 % sequence similarity with other bacterial species. The average nucleotide identity and genome-to-genome distance values between strain IMCC9719T and L. pacifica JCM 18388T were 71.7 and 16.9 %, respectively. The DNA G+C content of strain IMCC9719T was 43.5 mol%. Optimum growth of strain IMCC9719T was observed at 15 °C, at pH 7.5-8.5 and in the presence of 2.0-2.5 % (w/v) NaCl. The major fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c) and C16 : 0. Cells of strain IMCC9719T contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified polar lipid, an unidentified aminophospholipid and two unidentified phospholipids. The major respiratory quinone was ubiquinone-8 (Q-8). Based on the taxonomic data collected in this study, strain IMCC9719T represents a novel species of the genus Leucothrix, for which the name Leucothrix arctica sp. nov. is proposed. The type strain is IMCC9719T (=KACC 18010T=NBRC 110382T).}, } @article {pmid30516459, year = {2018}, author = {Ruan, CJ and Zheng, XW and Wang, J and Song, L and Zhu, YX and Du, WB and Lu, ZJ and Huang, Y and Huang, L and Dai, X}, title = {Hyphobacterium indicum sp. nov., isolated from deep seawater, and emended description of the genus Hyphobacterium.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3760-3765}, doi = {10.1099/ijsem.0.003054}, pmid = {30516459}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Indian Ocean ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A novel aerobic, Gram-stain-negative bacterium, designated strain 2ED5T, was isolated from a deep seawater sample in the north-west Indian Ocean. Cells of the strain were oval- to rod-shaped, and motile by a polar flagellum or sessile by a prostheca. The strain formed creamy white colonies on 2216E marine agar plates. It grew at 10-40 °C (optimum 28 °C) and pH 5.0-8.0 (optimum pH 6.0-7.0). The strain required 1-6 % (w/v) NaCl for growth and grew optimally in the presence of 2-3 % NaCl. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain 2ED5T was affiliated with the genus Hyphobacterium in the family Hyphomonadaceae of the class Alphaproteobacteria, sharing 95.1 % similarity at the 16S rRNA gene sequence level with the type strain of Hyphobacterium vulgare, the only species in the genus Hyphobacterium. The major fatty acids of the strain were C18 : 1ω7c and iso-C17 : 1ω9c, and the polar lipids included monoglycosyl diglyceride, sulfoquinovosyl diacylglycerol, glucuronopyranosyl diglyceride, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and an unidentified glycolipid. The strain contained ubiquinone Q-10 as the predominant respiratory quinone. The G+C content of the genomic DNA of the strain was 60.9 mol%. Based on the results of this polyphasic analysis, strain 2ED5T represents a novel species in the genus Hyphobacterium, for which the name Hyphobacterium indicum sp. nov. is proposed. The type strain is 2ED5T (=CGMCC 1.16466T=JCM 32612T).}, } @article {pmid30516458, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 9, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3685-3687}, doi = {10.1099/ijsem.0.003030}, pmid = {30516458}, issn = {1466-5034}, } @article {pmid30516032, year = {2019}, author = {Danchin, A}, title = {Conceptual sequel to biological expeditions at the time of global changes.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {38-40}, doi = {10.1111/1758-2229.12722}, pmid = {30516032}, issn = {1758-2229}, } @article {pmid30515580, year = {2018}, author = {Rodrigues, SV and Laviniki, V and Borges, KA and Furian, TQ and Moraes, HLS and Nascimento, VP and Salle, CTP}, title = {Biofilm Formation by Avian Pathogenic Escherichia coli is Not Related to In Vivo Pathogenicity.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1608-8}, pmid = {30515580}, issn = {1432-0991}, abstract = {Avian pathogenic Escherichia coli (APEC) is one of the pathogens that most concerns the poultry industry worldwide due to the economic losses it can cause. APEC persistence and survival, both in the environment and in the host, may be a consequence of biofilm-producing capabilities. The aim of this study was to evaluate APEC strains' biofilm production and its relationship to in vivo pathogenicity. Two hundred thirty-eight APEC isolates from three different origins (broiler bedding material, cellulite lesions, and respiratory diseases) were selected. The in vivo pathogenicity index (PI) was determined. Biofilm formation was evaluated using a microplate assay with analysis of colony morphology in Congo Red agar in order to detect the phenotypic expression of curli fimbriae and cellulose. Regarding biofilm production, it was observed that 55.8% of the strains produced biofilms. In the morphological test, 88.2% of the isolates expressed one or both components at one of the temperatures at least, and 11.8% of the isolates did not express curli or cellulose. Cellulose production was significantly higher at 25 °C. On the other hand, curli production was significantly higher at 37 °C. The study data indicate that there is no association between biofilm production and in vivo pathogenicity.}, } @article {pmid30514951, year = {2018}, author = {Boyle, R}, title = {These dusty young stars are changing the rules of planet-building.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {20-23}, doi = {10.1038/d41586-018-07591-8}, pmid = {30514951}, issn = {1476-4687}, } @article {pmid30514950, year = {2018}, author = {Goodman, SN}, title = {How sure are you of your result? Put a number on it.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {7}, doi = {10.1038/d41586-018-07589-2}, pmid = {30514950}, issn = {1476-4687}, } @article {pmid30514949, year = {2018}, author = {Wild, S}, title = {Geologists are measuring bullet damage to ancient Middle Eastern settlements.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {18-19}, doi = {10.1038/d41586-018-07320-1}, pmid = {30514949}, issn = {1476-4687}, } @article {pmid30514948, year = {2018}, author = {Sohn, E}, title = {Meet the supervisors who helped to shape four scientists' careers.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {151-152}, doi = {10.1038/d41586-018-07594-5}, pmid = {30514948}, issn = {1476-4687}, } @article {pmid30514947, year = {2018}, author = {}, title = {Flu virus is a master shape-shifter.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {9}, doi = {10.1038/d41586-018-07583-8}, pmid = {30514947}, issn = {1476-4687}, } @article {pmid30514946, year = {2018}, author = {Eisenstein, M}, title = {Transparent tissues bring cells into focus for microscopy.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {147-149}, doi = {10.1038/d41586-018-07593-6}, pmid = {30514946}, issn = {1476-4687}, } @article {pmid30514945, year = {2018}, author = {}, title = {The secrets of Lonesome George.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {5-6}, doi = {10.1038/d41586-018-07630-4}, pmid = {30514945}, issn = {1476-4687}, } @article {pmid30514944, year = {2018}, author = {Powell, K}, title = {Do luxe labs shape science?.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {36-38}, doi = {10.1038/d41586-018-07623-3}, pmid = {30514944}, issn = {1476-4687}, } @article {pmid30514943, year = {2018}, author = {Ravilious, K}, title = {Tehran's drastic sinking exposed by satellite data.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {17-18}, doi = {10.1038/d41586-018-07580-x}, pmid = {30514943}, issn = {1476-4687}, } @article {pmid30514942, year = {2018}, author = {Silver, A}, title = {China set to launch first-ever spacecraft to the far side of the Moon.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {15}, doi = {10.1038/d41586-018-07562-z}, pmid = {30514942}, issn = {1476-4687}, } @article {pmid30514941, year = {2018}, author = {}, title = {Light pulses prod artificial muscle into action.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {8}, doi = {10.1038/d41586-018-07582-9}, pmid = {30514941}, issn = {1476-4687}, } @article {pmid30514940, year = {2018}, author = {Del Bello, L}, title = {Venice anti-flood gates could wreck lagoon ecosystem.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {16}, doi = {10.1038/d41586-018-07372-3}, pmid = {30514940}, issn = {1476-4687}, } @article {pmid30514939, year = {2018}, author = {}, title = {A warning of future years both hot and dry.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {8}, doi = {10.1038/d41586-018-07567-8}, pmid = {30514939}, issn = {1476-4687}, } @article {pmid30514938, year = {2018}, author = {}, title = {Prehistoric Europeans feasted on caviar.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {9}, doi = {10.1038/d41586-018-07541-4}, pmid = {30514938}, issn = {1476-4687}, } @article {pmid30514937, year = {2018}, author = {Cyranoski, D}, title = {CRISPR-baby scientist fails to satisfy critics.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {13-14}, doi = {10.1038/d41586-018-07573-w}, pmid = {30514937}, issn = {1476-4687}, } @article {pmid30514936, year = {2018}, author = {}, title = {Siberian 'unicorns' grazed Asia less than 40,000 years ago.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {9}, doi = {10.1038/d41586-018-07543-2}, pmid = {30514936}, issn = {1476-4687}, } @article {pmid30514935, year = {2018}, author = {}, title = {Oil drilling linked to a spate of Los Angeles earthquakes.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {9}, doi = {10.1038/d41586-018-07542-3}, pmid = {30514935}, issn = {1476-4687}, } @article {pmid30514934, year = {2018}, author = {}, title = {A Thai dam devastates a rainforest and its birdlife.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {8}, doi = {10.1038/d41586-018-07489-5}, pmid = {30514934}, issn = {1476-4687}, } @article {pmid30514919, year = {2018}, author = {Georges, M and Charlier, C and Hayes, B}, title = {Harnessing genomic information for livestock improvement.}, journal = {Nature reviews. Genetics}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41576-018-0082-2}, pmid = {30514919}, issn = {1471-0064}, abstract = {The world demand for animal-based food products is anticipated to increase by 70% by 2050. Meeting this demand in a way that has a minimal impact on the environment will require the implementation of advanced technologies, and methods to improve the genetic quality of livestock are expected to play a large part. Over the past 10 years, genomic selection has been introduced in several major livestock species and has more than doubled genetic progress in some. However, additional improvements are required. Genomic information of increasing complexity (including genomic, epigenomic, transcriptomic and microbiome data), combined with technological advances for its cost-effective collection and use, will make a major contribution.}, } @article {pmid30514821, year = {2018}, author = {Cao, L and Zhang, R and Liu, T and Sun, Z and Hu, M and Sun, Y and Cheng, L and Guo, Y and Fu, S and Hu, J and Li, X and Yu, C and Wang, H and Chen, H and Li, X and Fry, EE and Stuart, DI and Qian, P and Lou, Z and Rao, Z}, title = {Seneca Valley virus attachment and uncoating mediated by its receptor anthrax toxin receptor 1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13087-13092}, doi = {10.1073/pnas.1814309115}, pmid = {30514821}, issn = {1091-6490}, support = {MR/N00065X/1//Medical Research Council/United Kingdom ; }, abstract = {Seneca Valley virus (SVV) is an oncolytic picornavirus with selective tropism for neuroendocrine cancers. SVV mediates cell entry by attachment to the receptor anthrax toxin receptor 1 (ANTXR1). Here we determine atomic structures of mature SVV particles alone and in complex with ANTXR1 in both neutral and acidic conditions, as well as empty "spent" particles in complex with ANTXR1 in acidic conditions by cryoelectron microscopy. SVV engages ANTXR1 mainly by the VP2 DF and VP1 CD loops, leading to structural changes in the VP1 GH loop and VP3 GH loop, which attenuate interprotomer interactions and destabilize the capsid assembly. Despite lying on the edge of the attachment site, VP2 D146 interacts with the metal ion in ANTXR1 and is required for cell entry. Though the individual substitution of most interacting residues abolishes receptor binding and virus propagation, a serine-to-alanine mutation at VP2 S177 significantly increases SVV proliferation. Acidification of the SVV-ANTXR1 complex results in a major reconfiguration of the pentameric capsid assemblies, which rotate ∼20° around the icosahedral fivefold axes to form a previously uncharacterized spent particle resembling a potential uncoating intermediate with remarkable perforations at both two- and threefold axes. These structures provide high-resolution snapshots of SVV entry, highlighting opportunities for anticancer therapeutic optimization.}, } @article {pmid30514820, year = {2018}, author = {Mazzola, F and Sunko, V and Khim, S and Rosner, H and Kushwaha, P and Clark, OJ and Bawden, L and Marković, I and Kim, TK and Hoesch, M and Mackenzie, AP and King, PDC}, title = {Itinerant ferromagnetism of the Pd-terminated polar surface of PdCoO2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12956-12960}, doi = {10.1073/pnas.1811873115}, pmid = {30514820}, issn = {1091-6490}, abstract = {The ability to modulate the collective properties of correlated electron systems at their interfaces and surfaces underpins the burgeoning field of "designer" quantum materials. Here, we show how an electronic reconstruction driven by surface polarity mediates a Stoner-like magnetic instability to itinerant ferromagnetism at the Pd-terminated surface of the nonmagnetic delafossite oxide metal PdCoO2 Combining angle-resolved photoemission spectroscopy and density-functional theory calculations, we show how this leads to a rich multiband surface electronic structure. We find similar surface state dispersions in PdCrO2, suggesting surface ferromagnetism persists in this sister compound despite its bulk antiferromagnetic order.}, } @article {pmid30514819, year = {2018}, author = {Yao, Y and Waters, JT and Shneidman, AV and Cui, J and Wang, X and Mandsberg, NK and Li, S and Balazs, AC and Aizenberg, J}, title = {Multiresponsive polymeric microstructures with encoded predetermined and self-regulated deformability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12950-12955}, doi = {10.1073/pnas.1811823115}, pmid = {30514819}, issn = {1091-6490}, abstract = {Dynamic functions of biological organisms often rely on arrays of actively deformable microstructures undergoing a nearly unlimited repertoire of predetermined and self-regulated reconfigurations and motions, most of which are difficult or not yet possible to achieve in synthetic systems. Here, we introduce stimuli-responsive microstructures based on liquid-crystalline elastomers (LCEs) that display a broad range of hierarchical, even mechanically unfavored deformation behaviors. By polymerizing molded prepolymer in patterned magnetic fields, we encode any desired uniform mesogen orientation into the resulting LCE microstructures, which is then read out upon heating above the nematic-isotropic transition temperature (TN-I) as a specific prescribed deformation, such as twisting, in- and out-of-plane tilting, stretching, or contraction. By further introducing light-responsive moieties, we demonstrate unique multifunctionality of the LCEs capable of three actuation modes: self-regulated bending toward the light source at T < TN-I, magnetic-field-encoded predetermined deformation at T > TN-I, and direction-dependent self-regulated motion toward the light at T > TN-I We develop approaches to create patterned arrays of microstructures with encoded multiple area-specific deformation modes and show their functions in responsive release of cargo, image concealment, and light-controlled reflectivity. We foresee that this platform can be widely applied in switchable adhesion, information encryption, autonomous antennae, energy harvesting, soft robotics, and smart buildings.}, } @article {pmid30514818, year = {2018}, author = {Schorsch, M and Kramer, M and Goss, T and Eisenhut, M and Robinson, N and Osman, D and Wilde, A and Sadaf, S and Brückler, H and Walder, L and Scheibe, R and Hase, T and Hanke, GT}, title = {A unique ferredoxin acts as a player in the low-iron response of photosynthetic organisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12111-E12120}, doi = {10.1073/pnas.1810379115}, pmid = {30514818}, issn = {1091-6490}, abstract = {Iron chronically limits aquatic photosynthesis, especially in marine environments, and the correct perception and maintenance of iron homeostasis in photosynthetic bacteria, including cyanobacteria, is therefore of global significance. Multiple adaptive mechanisms, responsive promoters, and posttranscriptional regulators have been identified, which allow cyanobacteria to respond to changing iron concentrations. However, many factors remain unclear, in particular, how iron status is perceived within the cell. Here we describe a cyanobacterial ferredoxin (Fed2), with a unique C-terminal extension, that acts as a player in iron perception. Fed2 homologs are highly conserved in photosynthetic organisms from cyanobacteria to higher plants, and, although they belong to the plant type ferredoxin family of [2Fe-2S] photosynthetic electron carriers, they are not involved in photosynthetic electron transport. As deletion of fed2 appears lethal, we developed a C-terminal truncation system to attenuate protein function. Disturbed Fed2 function resulted in decreased chlorophyll accumulation, and this was exaggerated in iron-depleted medium, where different truncations led to either exaggerated or weaker responses to low iron. Despite this, iron concentrations remained the same, or were elevated in all truncation mutants. Further analysis established that, when Fed2 function was perturbed, the classical iron limitation marker IsiA failed to accumulate at transcript and protein levels. By contrast, abundance of IsiB, which shares an operon with isiA, was unaffected by loss of Fed2 function, pinpointing the site of Fed2 action in iron perception to the level of posttranscriptional regulation.}, } @article {pmid30514817, year = {2018}, author = {Steenblock, C and Rubin de Celis, MF and Delgadillo Silva, LF and Pawolski, V and Brennand, A and Werdermann, M and Berger, I and Santambrogio, A and Peitzsch, M and Andoniadou, CL and Schally, AV and Bornstein, SR}, title = {Isolation and characterization of adrenocortical progenitors involved in the adaptation to stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12997-13002}, doi = {10.1073/pnas.1814072115}, pmid = {30514817}, issn = {1091-6490}, abstract = {The adrenal gland is a master regulator of the human body during response to stress. This organ shows constant replacement of senescent cells by newly differentiated cells. A high degree of plasticity is critical to sustain homeostasis under different physiological demands. This is achieved in part through proliferation and differentiation of adult adrenal progenitors. Here, we report the isolation and characterization of a Nestin+ population of adrenocortical progenitors located under the adrenal capsule and scattered throughout the cortex. These cells are interconnected with progenitors in the medulla. In vivo lineage tracing revealed that, under basal conditions, this population is noncommitted and slowly migrates centripetally. Under stress, this migration is greatly enhanced, and the cells differentiate into steroidogenic cells. Nestin+ cells cultured in vitro also show multipotency, as they differentiate into mineralocorticoid and glucocorticoid-producing cells, which can be further influenced by the exposure to Angiotensin II, adrenocorticotropic hormone, and the agonist of luteinizing hormone-releasing hormone, triptorelin. Taken together, Nestin+ cells in the adult adrenal cortex exhibit the features of adrenocortical progenitor cells. Our study provides evidence for a role of Nestin+ cells in organ homeostasis and emphasizes their role under stress. This cell population might be a potential source of cell replacement for the treatment of adrenal insufficiency.}, } @article {pmid30514816, year = {2018}, author = {Sokolov, AA and Zeidman, P and Erb, M and Ryvlin, P and Friston, KJ and Pavlova, MA}, title = {Structural and effective brain connectivity underlying biological motion detection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12034-E12042}, doi = {10.1073/pnas.1812859115}, pmid = {30514816}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 088130/Z/09/Z//Wellcome Trust/United Kingdom ; }, abstract = {The perception of actions underwrites a wide range of socio-cognitive functions. Previous neuroimaging and lesion studies identified several components of the brain network for visual biological motion (BM) processing, but interactions among these components and their relationship to behavior remain little understood. Here, using a recently developed integrative analysis of structural and effective connectivity derived from high angular resolution diffusion imaging (HARDI) and functional magnetic resonance imaging (fMRI), we assess the cerebro-cerebellar network for processing of camouflaged point-light BM. Dynamic causal modeling (DCM) informed by probabilistic tractography indicates that the right superior temporal sulcus (STS) serves as an integrator within the temporal module. However, the STS does not appear to be a "gatekeeper" in the functional integration of the occipito-temporal and frontal regions: The fusiform gyrus (FFG) and middle temporal cortex (MTC) are also connected to the right inferior frontal gyrus (IFG) and insula, indicating multiple parallel pathways. BM-specific loops of effective connectivity are seen between the left lateral cerebellar lobule Crus I and right STS, as well as between the left Crus I and right insula. The prevalence of a structural pathway between the FFG and STS is associated with better BM detection. Moreover, a canonical variate analysis shows that the visual sensitivity to BM is best predicted by BM-specific effective connectivity from the FFG to STS and from the IFG, insula, and STS to the early visual cortex. Overall, the study characterizes the architecture of the cerebro-cerebellar network for BM processing and offers prospects for assessing the social brain.}, } @article {pmid30514815, year = {2018}, author = {Schulze-Gahmen, U and Hurley, JH}, title = {Structural mechanism for HIV-1 TAR loop recognition by Tat and the super elongation complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12973-12978}, doi = {10.1073/pnas.1806438115}, pmid = {30514815}, issn = {1091-6490}, support = {P50 GM082250/GM/NIGMS NIH HHS/United States ; R01 GM124149/GM/NIGMS NIH HHS/United States ; P30 GM124169/GM/NIGMS NIH HHS/United States ; }, abstract = {Promoter-proximal pausing by RNA polymerase II (Pol II) is a key regulatory step in human immunodeficiency virus-1 (HIV-1) transcription and thus in the reversal of HIV latency. By binding to the nascent transactivating response region (TAR) RNA, HIV-1 Tat recruits the human super elongation complex (SEC) to the promoter and releases paused Pol II. Structural studies of TAR interactions have been largely focused on interactions between the TAR bulge and the arginine-rich motif (ARM) of Tat. Here, the crystal structure of the TAR loop in complex with Tat and the SEC core was determined at a 3.5-Å resolution. The bound TAR loop is stabilized by cross-loop hydrogen bonds. It makes structure-specific contacts with the side chains of the Cyclin T1 Tat-TAR recognition motif (TRM) and the zinc-coordinating loop of Tat. The TAR loop phosphate backbone forms electrostatic and VDW interactions with positively charged side chains of the CycT1 TRM. Mutational analysis showed that these interactions contribute importantly to binding affinity. The Tat ARM was present in the crystallized construct; however, it was not visualized in the electron density, and the TAR bulge was not formed in the RNA construct used in crystallization. Binding assays showed that TAR bulge-Tat ARM interactions contribute less to TAR binding affinity than TAR loop interactions with the CycT1 TRM and Tat core. Thus, the TAR loop evolved to make high-affinity interactions with the TRM while Tat has three roles: scaffolding and stabilizing the TRM, making specific interactions through its zinc-coordinating loop, and making electrostatic interactions through its ARM.}, } @article {pmid30514814, year = {2018}, author = {Zhao, C and Zayed, O and Yu, Z and Jiang, W and Zhu, P and Hsu, CC and Zhang, L and Tao, WA and Lozano-Durán, R and Zhu, JK}, title = {Leucine-rich repeat extensin proteins regulate plant salt tolerance in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13123-13128}, doi = {10.1073/pnas.1816991115}, pmid = {30514814}, issn = {1091-6490}, abstract = {The perception and relay of cell-wall signals are critical for plants to regulate growth and stress responses, but the underlying mechanisms are poorly understood. We found that the cell-wall leucine-rich repeat extensins (LRX) 3/4/5 are critical for plant salt tolerance in Arabidopsis The LRXs physically associate with the RAPID ALKALINIZATION FACTOR (RALF) peptides RALF22/23, which in turn interact with the plasma membrane-localized receptor-like protein kinase FERONIA (FER). The lrx345 triple mutant as well as fer mutant plants display retarded growth and salt hypersensitivity, which are mimicked by overexpression of RALF22/23 Salt stress promotes S1P protease-dependent release of mature RALF22 peptides. Treatment of roots with mature RALF22/23 peptides or salt stress causes the internalization of FER. Our results suggest that the LRXs, RALFs, and FER function as a module to transduce cell-wall signals to regulate plant growth and salt stress tolerance.}, } @article {pmid30514813, year = {2019}, author = {Thompson, TQ and Bellinger, MR and O'Rourke, SM and Prince, DJ and Stevenson, AE and Rodrigues, AT and Sloat, MR and Speller, CF and Yang, DY and Butler, VL and Banks, MA and Miller, MR}, title = {Anthropogenic habitat alteration leads to rapid loss of adaptive variation and restoration potential in wild salmon populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {177-186}, doi = {10.1073/pnas.1811559115}, pmid = {30514813}, issn = {1091-6490}, abstract = {Phenotypic variation is critical for the long-term persistence of species and populations. Anthropogenic activities have caused substantial shifts and reductions in phenotypic variation across diverse taxa, but the underlying mechanism(s) (i.e., phenotypic plasticity and/or genetic evolution) and long-term consequences (e.g., ability to recover phenotypic variation) are unclear. Here we investigate the widespread and dramatic changes in adult migration characteristics of wild Chinook salmon caused by dam construction and other anthropogenic activities. Strikingly, we find an extremely robust association between migration phenotype (i.e., spring-run or fall-run) and a single locus, and that the rapid phenotypic shift observed after a recent dam construction is explained by dramatic allele frequency change at this locus. Furthermore, modeling demonstrates that continued selection against the spring-run phenotype could rapidly lead to complete loss of the spring-run allele, and an empirical analysis of populations that have already lost the spring-run phenotype reveals they are not acting as sustainable reservoirs of the allele. Finally, ancient DNA analysis suggests the spring-run allele was abundant in historical habitat that will soon become accessible through a large-scale restoration (i.e., dam removal) project, but our findings suggest that widespread declines and extirpation of the spring-run phenotype and allele will challenge reestablishment of the spring-run phenotype in this and future restoration projects. These results reveal the mechanisms and consequences of human-induced phenotypic change and highlight the need to conserve and restore critical adaptive variation before the potential for recovery is lost.}, } @article {pmid30514812, year = {2018}, author = {Riggle, BA and Sinharay, S and Schreiber-Stainthorp, W and Munasinghe, JP and Maric, D and Prchalova, E and Slusher, BS and Powell, JD and Miller, LH and Pierce, SK and Hammoud, DA}, title = {MRI demonstrates glutamine antagonist-mediated reversal of cerebral malaria pathology in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12024-E12033}, doi = {10.1073/pnas.1812909115}, pmid = {30514812}, issn = {1091-6490}, abstract = {The deadliest complication of Plasmodium falciparum infection is cerebral malaria (CM), with a case fatality rate of 15 to 25% in African children despite effective antimalarial chemotherapy. No adjunctive treatments are yet available for this devastating disease. We previously reported that the glutamine antagonist 6-diazo-5-oxo-l-norleucine (DON) rescued mice from experimental CM (ECM) when administered late in the infection, a time by which mice had already suffered blood-brain barrier (BBB) dysfunction, brain swelling, and hemorrhaging. Herein, we used longitudinal MR imaging to visualize brain pathology in ECM and the impact of a new DON prodrug, JHU-083, on disease progression in mice. We demonstrate in vivo the reversal of disease markers in symptomatic, infected mice following treatment, including the resolution of edema and BBB disruption, findings usually associated with a fatal outcome in children and adults with CM. Our results support the premise that JHU-083 is a potential adjunctive treatment that could rescue children and adults from fatal CM.}, } @article {pmid30514751, year = {2018}, author = {Kundzewicz, ZW and Hegger, DLT and Matczak, P and Driessen, PPJ}, title = {Opinion: Flood-risk reduction: Structural measures and diverse strategies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12321-12325}, doi = {10.1073/pnas.1818227115}, pmid = {30514751}, issn = {1091-6490}, } @article {pmid30514581, year = {2019}, author = {Hui, C and Richardson, DM}, title = {How to Invade an Ecological Network.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {2}, pages = {121-131}, doi = {10.1016/j.tree.2018.11.003}, pmid = {30514581}, issn = {1872-8383}, abstract = {Invasion science is in a state of paradox, having low predictability despite strong, identifiable covariates of invasion performance. We propose shifting the foundation metaphor of biological invasions from a linear filtering scheme to one that invokes complex adaptive networks. We link invasion performance and invasibility directly to the loss of network stability and indirectly to network topology through constraints from the emergence of the stability criterion in complex systems. We propose the wind vane of an invaded network - the major axis of its adjacency matrix - which reveals how species respond dynamically to invasions. We suggest that invasion ecology should steer away from comparative macroecological studies, to rather explore the ecological network centred on the focal species.}, } @article {pmid30514580, year = {2019}, author = {Nicholson, E and Fulton, EA and Brooks, TM and Blanchard, R and Leadley, P and Metzger, JP and Mokany, K and Stevenson, S and Wintle, BA and Woolley, SNC and Barnes, M and Watson, JEM and Ferrier, S}, title = {Scenarios and Models to Support Global Conservation Targets.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {57-68}, doi = {10.1016/j.tree.2018.10.006}, pmid = {30514580}, issn = {1872-8383}, abstract = {Global biodiversity targets have far-reaching implications for nature conservation worldwide. Scenarios and models hold unfulfilled promise for ensuring such targets are well founded and implemented; here, we review how they can and should inform the Aichi Targets of the Strategic Plan for Biodiversity and their reformulation. They offer two clear benefits: providing a scientific basis for the wording and quantitative elements of targets; and identifying synergies and trade-offs by accounting for interactions between targets and the actions needed to achieve them. The capacity of scenarios and models to address complexity makes them invaluable for developing meaningful targets and policy, and improving conservation outcomes.}, } @article {pmid30514393, year = {2018}, author = {Green-Barber, JM and Old, JM}, title = {The genetic relatedness of a peri-urban population of eastern grey kangaroos.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {856}, pmid = {30514393}, issn = {1756-0500}, abstract = {OBJECTIVES: The genetic diversity of an eastern grey kangaroo (Macropus giganteus) population surrounded by landscape barriers was examined. DNA was extracted from tissue samples from 22 road-killed kangaroos, and blood samples from four live captured kangaroos. Amplified loci were used to determine relatedness between individual kangaroos. The level of relatedness and location of road-killed kangaroos were compared to evaluate spatial autocorrelation.

RESULTS: The expected and observed heterozygosity confirmed the loci were polymorphic and highly informative for use in this population. One pair of kangaroos were identified to be full siblings, and a high proportion were identified as half siblings. Six positive parentage assignments were detected. No correlation between relatedness and crossing site was detected.}, } @article {pmid30514377, year = {2018}, author = {Bedewi, N and Sisay, M and Edessa, D}, title = {Drug utilization pattern among pregnant women attending maternal and child health clinic of tertiary hospital in eastern Ethiopia: Consideration of toxicological perspectives.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {858}, pmid = {30514377}, issn = {1756-0500}, abstract = {OBJECTIVE: This study is aimed to investigate drug utilization pattern among pregnant women attending maternal and child health clinic of tertiary hospital in eastern Ethiopia from March 1 to April 20, 2018.

RESULT: A total of 369 pregnant women medical records were reviewed. The mean age of pregnant women was 24.34 (± 4.48) years and the majority of them were within the age of 18-25 years. About three-fourths (n = 277, 75.1%) of them were urban residents. Besides, 314 (85.1%) women had taken at least one drug with a total of 377 drugs prescribed. From which, supplemental drugs accounted majority of the drug therapy (84.88%) whereas non-supplemental drugs (15.12%) were used by 41 pregnant women during the review period. According to Food and Drug Administration FDA pregnancy risk classification, 320 (84.88%) drugs were prescribed from category A; 33 (8.75%) drugs were from category B; 19 (5.04%) drugs were from category C and 5 (1.33%) drugs were from category D. There was no drug prescribed from category X. As this result indicated, there is a decrease in the prevalence of drug use from Category A to X as the possibility of potential risk to fetus might outweigh the potential benefit to the mother. Some drugs were utilized from category D for treatment of chronic illnesses.}, } @article {pmid30514374, year = {2018}, author = {Gedif, G and Sisay, Y and Alebel, A and Belay, YA}, title = {Correction to: Level of job satisfaction and associated factors among health care professionals working at University of Gondar Referral Hospital, Northwest Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {857}, pmid = {30514374}, issn = {1756-0500}, abstract = {Following publication of the original article [1], the authors reported that one of the authors' names was spelled incorrectly. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.}, } @article {pmid30514372, year = {2018}, author = {Abdul-Cader, MS and De Silva Senapathi, U and Nagy, E and Sharif, S and Abdul-Careem, MF}, title = {Antiviral response elicited against avian influenza virus infection following activation of toll-like receptor (TLR)7 signaling pathway is attributable to interleukin (IL)-1β production.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {859}, pmid = {30514372}, issn = {1756-0500}, support = {AMN048//Canadian Poultry Research Council/ ; EQPEQ/421963-2012//Natural Sciences and Engineering/ ; 2011R037R//Alberta Agriculture and Forestry/ ; }, abstract = {OBJECTIVE: Single stranded ribonucleic acid (ssRNA) binds to toll-like receptor (TLR)7 leading to recruitment of immune cells and production of pro-inflammatory cytokines, which has been shown in mammals. In chickens, ssRNA has been shown to elicit antiviral response against infectious bursal disease virus infection. The objectives of this study were to determine the pro-inflammatory mediators that are activated downstream of TLR7 signaling pathway in avian macrophages and their roles in antiviral response against avian influenza virus (AIV) infection.

RESULTS: In this study, first, we stimulated avian macrophages with the analog of ssRNA, resiquimod, and found that the ssRNA was capable of increasing nitric oxide (NO) and interleukin (IL-1β) production in avian macrophages. Second, we observed when the avian macrophages were stimulated with ssRNA, it elicits an antiviral response against AIV. Finally, we demonstrated that when we blocked the IL-1β response using IL-1 receptor antagonist (IL-1Ra) and the NO production using a selective inhibitor of inducible nitric oxide synthase (iNOS), N-([3-(aminomethyl)phenyl]methyl)ethanimidamide dihydrochloride (1400 W), the antiviral response against AIV is attributable to IL-1β production and not to the NO production. This study provides insights into the mechanisms of antiviral response mediated by ssRNA, particularly against AIV infection.}, } @article {pmid30514370, year = {2018}, author = {Thapa, P and Thapa, A and Khadka, N and Bhattarai, R and Jha, S and Khanal, A and Basnet, B}, title = {YouTube lens to attention deficit hyperactivity disorder: a social media analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {854}, pmid = {30514370}, issn = {1756-0500}, abstract = {OBJECTIVE: Social media has provided an online environment for patients to discuss regarding their health and seek medical information. The primary aim of our study was to analyze the quality of information shared on YouTube regarding attention deficit hyperactivity disorder (ADHD).

RESULTS: More than half of the videos, 91 (57.23%) had duration of fewer than 5 min. Only 8 (5.03%) videos were rated as highly useful whereas 61 (38.36%) videos were misleading. Interestingly, there was a significant higher (1203.38 ± 395) likes in the misleading group of videos, compared to 162.13 ± 169.63 likes in the very useful group, P = 0.012. Only a small fraction of videos had very useful information on ADHD. There is a need for high-quality, evidence-based, educational videos on ADHD for patient education.}, } @article {pmid30514368, year = {2018}, author = {Singh, NK and Wood, JM and Karouia, F and Venkateswaran, K}, title = {Correction to: Succession and persistence of microbial communities and antimicrobial resistance genes associated with International Space Station environmental surfaces.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {214}, pmid = {30514368}, issn = {2049-2618}, abstract = {Following publication of the original article [1], the authors reported a typographic error in scientific notation in the number of reads, the text should read as.}, } @article {pmid30514367, year = {2018}, author = {Marasco, R and Mosqueira, MJ and Fusi, M and Ramond, JB and Merlino, G and Booth, JM and Maggs-Kölling, G and Cowan, DA and Daffonchio, D}, title = {Rhizosheath microbial community assembly of sympatric desert speargrasses is independent of the plant host.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {215}, pmid = {30514367}, issn = {2049-2618}, support = {95565//South African National Research Foundation/ ; }, abstract = {BACKGROUND: The rhizosheath-root system is an adaptive trait of sandy-desert speargrasses in response to unfavourable moisture and nutritional conditions. Under the deserts' polyextreme conditions, plants interact with edaphic microorganisms that positively affect their fitness and resistance. However, the trophic simplicity and environmental harshness of desert ecosystems have previously been shown to strongly influence soil microbial community assembly. We hypothesize that sand-driven ecological filtering constrains the microbial recruitment processes in the speargrass rhizosheath-root niche, prevailing over the plant-induced selection.

METHODS: Bacterial and fungal communities from the rhizosheath-root compartments (endosphere root tissues, rhizosheath and rhizosphere) of three Namib Desert speargrass species (Stipagrostis sabulicola, S. seelyae and Cladoraphis spinosa) along with bulk sand have been studied to test our hypothesis. To minimize the variability determined by edaphic and climatic factors, plants living in a single dune were studied. We assessed the role of plant species vs the sandy substrate on the recruitment and selection, phylogenetic diversity and co-occurrence microbial networks of the rhizosheath-root system microbial communities.

RESULTS: Microorganisms associated with the speargrass rhizosheath-root system were recruited from the surrounding bulk sand population and were significantly enriched in the rhizosheath compartments (105 and 104 of bacterial 16S rRNA and fungal ITS copies per gram of sand to up to 108 and 107 copies per gram, respectively). Furthermore, each rhizosheath-root system compartment hosted a specific microbial community demonstrating strong niche-partitioning. The rhizosheath-root systems of the three speargrass species studied were dominated by desert-adapted Actinobacteria and Alphaproteobacteria (e.g. Lechevalieria, Streptomyces and Microvirga) as well as saprophytic Ascomycota fungi (e.g. Curvularia, Aspergillus and Thielavia). Our results clearly showed a random phylogenetic turnover of rhizosheath-root system associated microbial communities, independent of the plant species, where stochastic factors drive neutral assembly. Co-occurrence network analyses also indicated that the bacterial and fungal community members of the rhizosheath-root systems established a higher number of interactions than those in the barren bulk sand, suggesting that the former are more stable and functional than the latter.

CONCLUSION: Our study demonstrates that the rhizosheath-root system microbial communities of desert dune speargrasses are stochastically assembled and host-independent. This finding supports the concept that the selection determined by the desert sand prevails over that imposed by the genotype of the different plant species.}, } @article {pmid30514365, year = {2018}, author = {Alam, MS and Kibria, MG and Jahan, N and Price, RN and Ley, B}, title = {Spectrophotometry assays to determine G6PD activity from Trinity Biotech and Pointe Scientific G6PD show good correlation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {855}, pmid = {30514365}, issn = {1756-0500}, support = {OPP1054404//Bill and Melinda Gates Foundation/ ; }, abstract = {OBJECTIVES: Spectrophotometry kits from Pointe Scientific (PS; USA) were compared to kits from Trinity Biotech (Trinity; Ireland) in 50 venous blood samples from purposively selected individuals in Bangladesh. Repeatability and inter-assay variability were assessed by Students t-test, Bland-Altman plot and Pearson correlation coefficient (r). The median glucose-6-phosphate dehydrogenase (G6PD) activity of all G6PD normal participants was calculated per assay and defined as 100% activity. Performance was calculated considering 30% and 70% cut off activities and Trinity as reference.

RESULTS: The intra-assay correlation of Trinity (r = 0.9841, p < 0.001) and PS (r = 0.9833, p < 0.001) did not differ significantly (p = 0.904). Both assays were closely correlated (r = 0.9799, p < 0.001), with a mean difference of 0.1 U/gHb (95% limit of agreement: - 1.32 to 1.57). At 30% cut off PS had a sensitivity of 100% (95% confidence interval (95 CI) 59.0-100.0) and specificity of 100% (95% CI 91.8 to 100.0), at 70% cut-off of 100% (95% CI 79.4-100.0) and 97.1% (95% CI 84.7-99.9) respectively. The G6PD assay from PS is a reliable alternative to the assay from Trinity.}, } @article {pmid30514360, year = {2018}, author = {Keel, BN and Nonneman, DJ and Lindholm-Perry, AK and Oliver, WT and Rohrer, GA}, title = {Porcine single nucleotide polymorphisms and their functional effect: an update.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {860}, pmid = {30514360}, issn = {1756-0500}, abstract = {OBJECTIVE: To aid in the development of a comprehensive list of functional variants in the swine genome, single nucleotide polymorphisms (SNP) were identified from whole genome sequence of 240 pigs. Interim data from 72 animals in this study was published in 2017. This communication extends our previous work not only by utilizing genomic sequence from additional animals, but also by the use of the newly released Sscrofa 11.1 reference genome.

RESULTS: A total of 26,850,263 high confidence SNP were identified, including 19,015,267 reported in our previously published results. Variation was detected in the coding sequence or untranslated regions (UTR) of 78% of the genes in the porcine genome: 1729 loss-of-function variants were predicted in 1162 genes, 12,686 genes contained 64,232 nonsynonymous variants, 250,403 variants were present in UTR of 15,739 genes, and 15,284 genes contained 90,939 synonymous variants. In total, approximately 316,000 SNP were classified as being of high to moderate impact (i.e. loss-of-function, nonsynonymous, or regulatory). These high to moderate impact SNP will be the focus of future genome-wide association studies.}, } @article {pmid30514356, year = {2018}, author = {Bernerth, K and Schiefke, I and Liebscher, K and Raczynski, S and Kottmann, T and Teich, N}, title = {Factor-XIII activity in patients with mild to moderate ulcerative colitis and active bleeding: a prospective observational study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {853}, pmid = {30514356}, issn = {1756-0500}, abstract = {OBJECTIVE: Coagulation factor XIII plays a key role in fibrin clot stabilization and epithelial healing. Under chronic inflammatory conditions involving bleeding and an activation of the coagulation cascade, the FXIIIa inversely correlate with disease activity. We assumed that FXIIIa could be a predictor of severity in patients with ulcerative colitis (UC). Here, we evaluated the course of plasma activity of FXIIIa in 49 patients with mild to moderate UC and active rectal bleeding. Patients with a partial Mayo bleeding subscore > 2 were eligible to participate in our prospective observational study in an outpatient setting. FXIIIa was investigated during acute flare conditions, after bleeding had stopped and later on in quiescent UC.

RESULTS: Plasma activity of FXIIIa did not show any significant differences during the UC course. FXIIIa was measured below normal range < 70% in only 8 patients during the flare and increased to normal values during follow-up in 7 of these patients. Low FXIIIa during the flare was not associated with an increased bleeding activity. In patients with a mild to moderate UC flare and prolonged bleeding, FXIIIa activity is neither predictive of UC severity nor of any bleeding activity in an outpatient setting. Trial registration This non interventional, non pharmacological prospective study was not obligated to receive a unique identifying number. This trial is registered with the Ethics Committee of the State Medical Chamber of Saxony, Dresden, Germany (Clinical Trials Registry number EK-BR-03/14-1).}, } @article {pmid30514321, year = {2018}, author = {Tan, SN and Sim, SP and Khoo, ASB}, title = {Matrix association region/scaffold attachment region (MAR/SAR) sequence: its vital role in mediating chromosome breakages in nasopharyngeal epithelial cells via oxidative stress-induced apoptosis.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {15}, pmid = {30514321}, issn = {1471-2199}, support = {06-065//Ministry of Health, Malaysia/ ; }, abstract = {BACKGROUND: Oxidative stress is known to be involved in most of the aetiological factors of nasopharyngeal carcinoma (NPC). Cells that are under oxidative stress may undergo apoptosis. We have previously demonstrated that oxidative stress-induced apoptosis could be a potential mechanism mediating chromosome breakages in nasopharyngeal epithelial cells. Additionally, caspase-activated DNase (CAD) may be the vital player in mediating the chromosomal breakages during oxidative stress-induced apoptosis. Chromosomal breakage occurs during apoptosis and chromosome rearrangement. Chromosomal breakages tend to cluster in certain regions, such as matrix association region/scaffold attachment region (MAR/SAR). We hypothesised that oxidative stress-induced apoptosis may result in chromosome breaks preferentially at the MAR/SAR sites. The AF9 gene at 9p22 was targeted in this study because 9p22 is a deletion site commonly found in NPC.

RESULTS: By using MAR/SAR recognition signature (MRS), potential MAR/SAR sites were predicted in the AF9 gene. The predicted MAR/SAR sites precisely match to the experimentally determined MAR/SARs. Hydrogen peroxide (H2O2) was used to induce apoptosis in normal nasopharyngeal epithelial cells (NP69) and NPC cells (HK1). Nested inverse polymerase chain reaction was employed to identify the AF9 gene cleavages. In the SAR region, the gene cleavage frequency of H2O2-treated cells was significantly higher than that of the non-treated cells. A few chromosomal breakages were detected within the AF9 region which was previously found to be involved in the mixed lineage leukaemia (MLL)-AF9 translocation in an acute lymphoblastic leukaemia patient. As for the non-SAR region, no significant difference in the gene cleavage frequency was found between the untreated control and H2O2-treated cells. Furthermore, H2O2-induced cleavages within the SAR region were reduced by caspase-3 inhibitor, which indirectly inhibits CAD.

CONCLUSIONS: These results reaffirm our previous findings that oxidative stress-induced apoptosis could be one of the potential mechanisms underlying chromosome breakages in nasopharyngeal epithelial cells. MAR/SAR may play a vital role in defining the location of chromosomal breakages mediated by oxidative stress-induced apoptosis, where CAD is the major nuclease.}, } @article {pmid30514299, year = {2018}, author = {Wang, L and Yang, Z and Zhang, B and Yu, D and Liu, J and Gong, Q and Qanmber, G and Li, Y and Lu, L and Lin, Y and Yang, Z and Li, F}, title = {Genome-wide characterization and phylogenetic analysis of GSK gene family in three species of cotton: evidence for a role of some GSKs in fiber development and responses to stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {330}, pmid = {30514299}, issn = {1471-2229}, support = {No. 31501345//the National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Cotton Fiber ; Gene Duplication/genetics ; Gene Expression Regulation, Plant ; Genes, Plant/genetics/physiology ; Genome-Wide Association Study ; Glycogen Synthase Kinase 3/*genetics/metabolism/physiology ; Gossypium/*genetics/metabolism/physiology ; Phylogeny ; Plant Proteins/*genetics/metabolism/physiology ; RNA, Plant/genetics ; Real-Time Polymerase Chain Reaction ; Stress, Physiological/genetics/physiology ; }, abstract = {BACKGROUND: The glycogen synthase kinase 3/shaggy kinase (GSK3) is a serine/threonine kinase with important roles in animals. Although GSK3 genes have been studied for more than 30 years, plant GSK genes have been studied only since the last decade. Previous research has confirmed that plant GSK genes are involved in diverse processes, including floral development, brassinosteroid signaling, and responses to abiotic stresses.

RESULT: In this study, 20, 15 (including 5 different transcripts) and 10 GSK genes were identified in G. hirsutum, G. raimondii and G. arboreum, respectively. A total of 65 genes from Arabidopsis, rice, and cotton were classified into 4 clades. High similarities were found in GSK3 protein sequences, conserved motifs, and gene structures, as well as good concordance in gene pairwise comparisons (G. hirsutum vs. G. arboreum, G. hirsutum vs. G. raimondii, and G. arboreum vs. G. raimondii) were observed. Whole genome duplication (WGD) within At and Dt sub-genomes has been central to the expansion of the GSK gene family. Furthermore, GhSK genes showed diverse expression patterns in various tissues. Additionally, the expression profiles of GhSKs under different stress treatments demonstrated that many are stress-responsive genes. However, none were induced by brassinolide treatment. Finally, nine co-expression sub-networks were observed for GhSKs and the functional annotations of these genes suggested that some GhSKs might be involved in cotton fiber development.

CONCLUSION: In this present work, we identified 45 GSK genes from three cotton species, which were divided into four clades. The gene features, muti-alignment, conversed motifs, and syntenic blocks indicate that they have been highly conserved during evolution. Whole genome duplication was determined to be the dominant factor for GSK gene family expansion. The analysis of co-expressed sub-networks and tissue-specific expression profiles suggested functions of GhSKs during fiber development. Moreover, their different responses to various abiotic stresses indicated great functional diversity amongst the GhSKs. Briefly, data presented herein may serve as the basis for future functional studies of GhSKs.}, } @article {pmid30514281, year = {2018}, author = {Cianchetti-Benedetti, M and Dell'Omo, G and Russo, T and Catoni, C and Quillfeldt, P}, title = {Interactions between commercial fishing vessels and a pelagic seabird in the southern Mediterranean Sea.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {54}, pmid = {30514281}, issn = {1472-6785}, support = {PQ 148/8//Deutsche Forschungsgemeinschaft/ ; PQ 148/17//Deutsche Forschungsgemeinschaft/ ; 000093//LIFE11 + NAT/IT// ; }, abstract = {BACKGROUND: Fishing activities can influence foraging behaviour of many seabird species worldwide. Seabirds are attracted by fishing vessels which can facilitate access to demersal fish as a novel food resource that otherwise would be unavailable. On the other hand, intense fishing activities cause depletion of fish stocks with a reduction of natural prey available for seabirds. Moreover, fisheries discards can have lower nutritional value than natural prey. However, the importance of fisheries discard for seabirds and the possible implications on their foraging ecology is still poorly understood. In this study, we analysed the interactions of Scopoli's shearwaters (Calonectris diomedea) during their foraging trips with fishing vessels. We combined the GPS and accelerometer data of shearwaters with the GPS data gathered during the same period from fishing vessels. Accelerometers allowed us to identify the main behaviours of birds.

RESULTS: The presence of fishing vessels significantly affected the individual behaviour of Scopoli's shearwaters. Birds increased the time spent sitting on the water within 1.28 ± 0.13 km of fishing vessels likely feeding or waiting for discards. Approaches towards vessels within the interaction distance were therefore classified as an interaction and were recorded in about 40% of individuals. Birds interacting with fisheries had longer flight time during their foraging trips and covered longer distances to reach more distant foraging areas compared with individuals not approaching vessels.

CONCLUSIONS: Our results suggested that fisheries discard consumption might not be a profitable source of food for Scopoli's shearwaters. Despite the high density of fishing vessels in the home range of Scopoli's shearwater, most individuals did not interact with them. Accordingly, scavenging individuals showed a lower foraging efficiency than their conspecifics. Intraspecific competition for foraging areas might play an important role for the foraging decision of birds to consume fisheries discards.}, } @article {pmid30514265, year = {2018}, author = {Ryalls, JMW and Moore, BD and Johnson, SN}, title = {Silicon uptake by a pasture grass experiencing simulated grazing is greatest under elevated precipitation.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {53}, pmid = {30514265}, issn = {1472-6785}, support = {ARC DP14100636//Australian Research Council/ ; DP170102278//Australian Research Council/ ; FT170100342//Australian Research Council/ ; }, abstract = {BACKGROUND: Grasses are hyper-accumulators of silicon (Si) and often up-regulate Si following herbivory. Positive correlations exist between Si and plant water content, yet the extent to which Si uptake responses can be mediated by changes in soil water availability has rarely been studied and never, to our knowledge, under field conditions. We used field-based rain-exclusion shelters to investigate how simulated grazing (shoot clipping) and altered rainfall patterns (drought and elevated precipitation, representing 50% and 150% of ambient precipitation levels, respectively) affected initial patterns of root- and shoot-Si uptake in a native Australian grass (Microlaena stipoides) in Si-supplemented and untreated soils.

RESULTS: Si supplementation increased soil water retention under ambient and elevated precipitation but not under drought, although this had little effect on Si uptake and growth (tiller numbers or root biomass) of M. stipoides. Changes in rainfall patterns and clipping had strong individual effects on plant growth and Si uptake and storage, whereby clipping increased Si uptake by M. stipoides under all rainfall treatments but to the greatest extent under elevated precipitation. Moreover, above-ground-below-ground Si distribution only changed following elevated precipitation by decreasing the ratio of root:shoot Si concentrations.

CONCLUSIONS: Results highlight the importance of soil water availability for Si uptake and suggest a role for both active and passive Si transport mechanisms. Such manipulative field studies may provide a more realistic insight into how grasses initially respond to herbivory in terms of Si-based defence under different environmental conditions.}, } @article {pmid30514254, year = {2018}, author = {Rather, RA and Srinivasan, V and Anwar, M}, title = {Seasonal deviation effects foliar endophyte assemblage and diversity in Asparagus racemosus and Hemidesmus indicus.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {52}, pmid = {30514254}, issn = {1472-6785}, abstract = {BACKGROUND: Fungal endophytes are the living symbionts which cause no apparent damage to the host tissue. The distribution pattern of these endophytes within a host plant is mediated by environmental factors. This study was carried out to explore the fungal endophyte community and their distribution pattern in Asparagus racemosus and Hemidesmus indicus growing in the study area.

RESULTS: Foliar endophytes were isolated for 2 years from A. racemosus and H. indicus at four different seasons (June-August, September-November, December-February, March-May). A total of 5400 (675/season/year) leaf segments harbored 38 fungal species belonging to 17 genera, 12 miscellaneous mycelia sterile from 968 isolates and 13 had yeast like growth. In A. racemosus, Acremonium strictum and Phomopsis sp.1, were dominant with overall relative colonization densities (RCD) of 7.11% and 5.44% respectively, followed by Colletotrichum sp.3 and Colletotrichum sp.1 of 4.89% and 4.83% respectively. In H. indicus the dominant species was A. strictum having higher overall RCD of 5.06%, followed by Fusarium moniliforme and Colletotrichum sp.2 with RCD of 3.83% and 3%, respectively. Further the overall colonization and isolation rates were higher during the wet periods (September-November) in both A. racemosus (92.22% and 95.11%) and H. indicus (82% and 77.11%).

CONCLUSION: Study samples treated with 0.2% HgCl2 and 75% EtOH for 30 s and 1 min, respectively, confirmed most favorable method of isolation of the endophytes. Owing to high mean isolation and colonization rates, September-November season proved to be the optimal season for endophyte isolation in both the study plants. Assessing the bioactive potential of these endophytes, may lead to the isolation of novel natural products and metabolites.}, } @article {pmid30514253, year = {2018}, author = {Buhk, C and Oppermann, R and Schanowski, A and Bleil, R and Lüdemann, J and Maus, C}, title = {Flower strip networks offer promising long term effects on pollinator species richness in intensively cultivated agricultural areas.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {55}, pmid = {30514253}, issn = {1472-6785}, support = {610996063//Bayer AG/ ; 611132244//Bayer AG/ ; 611755309//Bayer AG/ ; }, abstract = {BACKGROUND: Intensively cultivated agricultural landscapes often suffer from substantial pollinator losses, which may be leading to decreasing pollination services for crops and wild flowering plants. Conservation measures that are easy to implement and accepted by farmers are needed to halt a further loss of pollinators in large areas under intensive agricultural management. Here we report the results of a replicated long-term study involving networks of mostly perennial flower strips covering 10% of a conventionally managed agricultural landscape in southwestern Germany.

RESULTS: We demonstrate the considerable success of these measures for wild bee and butterfly species richness over an observation period of 5 years. Overall species richness of bees and butterflies but also the numbers of specialist bee species clearly increased in the ecological enhancement areas as compared to the control areas without ecological enhancement measures. A three to five-fold increase in species richness was found after more than 2 years of enhancement of the areas with flower strips. Oligolectic bee species increased significantly only after the third year.

CONCLUSIONS: In our long-term field experiment we used a large variety of seed mixtures and temporal variation in seeding time, ensured continuity of the flower-strips by using perennial seed mixtures and distributed the measures over c. 10% of the landscape. This led to an increase in pollinator abundance, suggesting that these measures may be instrumental for the successful support of pollinators. These measures may ensure the availability of a network of diverse habitats and foraging resources for pollinators throughout the year, as well as nesting sites for many species. The measures are applied in-field and are suitable for application in areas under intensive agriculture. We propose that flower strip networks should be implemented much more in the upcoming CAP (common agricultural policy) reform in the European Union and promoted more by advisory services for farmers.}, } @article {pmid30514240, year = {2018}, author = {Zhang, Z and Dunwell, JM and Zhang, YM}, title = {An integrated omics analysis reveals molecular mechanisms that are associated with differences in seed oil content between Glycine max and Brassica napus.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {328}, pmid = {30514240}, issn = {1471-2229}, support = {31571268, 31871242//National Natural Science Foundation of China/ ; 2014RC020//Huazhong Agricultural University Scientific & Technological Self-innovation Foundation/ ; CB2017B01//State Key Laboratory of Cotton Biology Open Fund/ ; }, mesh = {Arabidopsis/chemistry/genetics/metabolism ; Brassica napus/chemistry/genetics/*metabolism ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Lipids/biosynthesis ; Metabolic Networks and Pathways/genetics ; MicroRNAs/genetics ; Phylogeny ; Plant Oils/analysis/metabolism ; Rapeseed Oil/*analysis/metabolism ; Seeds/*chemistry ; Sequence Alignment ; Sesamum/chemistry/genetics/metabolism ; Soybean Oil/*analysis/metabolism ; Soybeans/chemistry/genetics/*metabolism ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Rapeseed (Brassica napus L.) and soybean (Glycine max L.) seeds are rich in both protein and oil, which are major sources of biofuels and nutrition. Although the difference in seed oil content between soybean (~ 20%) and rapeseed (~ 40%) exists, little is known about its underlying molecular mechanism.

RESULTS: An integrated omics analysis was performed in soybean, rapeseed, Arabidopsis (Arabidopsis thaliana L. Heynh), and sesame (Sesamum indicum L.), based on Arabidopsis acyl-lipid metabolism- and carbon metabolism-related genes. As a result, candidate genes and their transcription factors and microRNAs, along with phylogenetic analysis and co-expression network analysis of the PEPC gene family, were found to be largely associated with the difference between the two species. First, three soybean genes (Glyma.13G148600, Glyma.13G207900 and Glyma.12G122900) co-expressed with GmPEPC1 are specifically enriched during seed storage protein accumulation stages, while the expression of BnPEPC1 is putatively inhibited by bna-miR169, and two genes BnSTKA and BnCKII are co-expressed with BnPEPC1 and are specifically associated with plant circadian rhythm, which are related to seed oil biosynthesis. Then, in de novo fatty acid synthesis there are rapeseed-specific genes encoding subunits β-CT (BnaC05g37990D) and BCCP1 (BnaA03g06000D) of heterogeneous ACCase, which could interfere with synthesis rate, and β-CT is positively regulated by four transcription factors (BnaA01g37250D, BnaA02g26190D, BnaC01g01040D and BnaC07g21470D). In triglyceride synthesis, GmLPAAT2 is putatively inhibited by three miRNAs (gma-miR171, gma-miR1516 and gma-miR5775). Finally, in rapeseed there was evidence for the expansion of gene families, CALO, OBO and STERO, related to lipid storage, and the contraction of gene families, LOX, LAH and HSI2, related to oil degradation.

CONCLUSIONS: The molecular mechanisms associated with differences in seed oil content provide the basis for future breeding efforts to improve seed oil content.}, } @article {pmid30514233, year = {2018}, author = {Chochlakis, D and Santos, AS and Giadinis, ND and Papadopoulos, D and Boubaris, L and Kalaitzakis, E and Psaroulaki, A and Kritas, SK and Petridou, EI}, title = {Genotyping of Coxiella burnetii in sheep and goat abortion samples.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {204}, pmid = {30514233}, issn = {1471-2180}, abstract = {BACKGROUND: Q fever, caused by Coxiella burnetii, is a zoonosis that presents a worldwide distribution and affects both humans and animals. The route of dispersal of the pathogen by ruminants into the environment usually involves stages of abortion and parturition, nevertheless the agent can, also, be detected in other animal samples. Therefore it is considered as important in terms of proper diagnosis, as well as, for epidemiology and surveillance purposes, to genotype the pathogen. The aim of the current study was to investigate the presence of different genotypes of the agent in animals that had suffered from abortion during a two-year survey in Greece.

RESULTS: Sixty nine tissue samples (37 stomach contents, 11 liver samples, 21 cotyledons) were collected from 59 abortion cases in sheep (N = 45) and goats (N = 14) from 65 farms at eight different areas of Greece. Samples were screened by qPCR and positive ones were further genotyped using a 10-locus multiple loci (ms 1, 3, 7, 12, 20, 21, 22, 26, 30 and 36) variable number of tandem repeat analysis (MLVA) method. Three genotypes were identified in sheep (A, B, C). Samples representing each of the obtained MLVA profile were further used for MST genotyping. Ten spacers (Cox 2, 5, 6, 18, 20, 22, 37, 51, 56 and 57) were amplified. A close relatedness among the identified MLVA genotypes was confirmed since they all belonged to MST group 32.

CONCLUSIONS: The current study introduces into the aspect of genotyping of C. burnetii in Greece. Further studies are needed to explore the presence of more genotypes, to associate the genotypes circulating in the animal and tick population with those causing human disease in order to further expand on the epidemiological aspects of the pathogen.}, } @article {pmid30514222, year = {2018}, author = {Castillo, FM and Canales, J and Claude, A and Calderini, DF}, title = {Expansin genes expression in growing ovaries and grains of sunflower are tissue-specific and associate with final grain weight.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {327}, pmid = {30514222}, issn = {1471-2229}, support = {1141048//Consejo Nacional de Innovación, Ciencia y Tecnología/ ; postgraduate scholarships//Consejo Nacional de Innovación, Ciencia y Tecnología/ ; }, mesh = {Edible Grain/growth & development/*metabolism ; Flowers/*metabolism ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Genetic Association Studies ; Helianthus/genetics/growth & development/*metabolism ; Phylogeny ; Plant Proteins/*metabolism ; }, abstract = {BACKGROUND: Grain weight (GW) is a key component of sunflower yield and quality, but may be limited by maternal tissues. Cell growth is influenced by expansin proteins that loosen the plant cell wall. This study aimed to identify spatio-temporal expression of EXPN genes in sunflower reproductive organ tissues (ovary, pericarp, and embryo) and evaluate correlations between reproductive organ growth and expansin genes expression. Evaluations involved eight different developmental stages, two genotypes, two source-sink treatments and two experiments. The genotypes evaluated are contrasting in GW (Alybro and confection variety RHA280) under two source-sink treatments (control and shaded) to study the interactions between grain growth and expansin genes expression.

RESULTS: Ovaries and grains were sampled at pre- and post-anthesis, respectively. Final GW differed between genotypes and shading treatments. Shading treatment decreased final GW by 16.4 and 19.5% in RHA280 and Alybro, respectively. Relative expression of eight expansin genes were evaluated in grain tissues. EXPN4 was the most abundant expansin in the ovary tissue, while EXPN10 and EXPN7 act predominantly in ovary and pericarp tissues, and EXPN1 and EXPN15 in the embryo tissues.

CONCLUSIONS: Specific expansin genes were expressed in ovary, pericarp and embryo in a tissue-specific manner. Differential expression among grain tissues was consistent between genotypes, source-sink treatments and experiments. The correlation analysis suggests that EXPN genes could be specifically involved in grain tissue extension, and their expression could be linked to grain size in sunflower.}, } @article {pmid30514219, year = {2018}, author = {Ruan, MB and Yang, YL and Li, KM and Guo, X and Wang, B and Yu, XL and Peng, M}, title = {Identification and characterization of drought-responsive CC-type glutaredoxins from cassava cultivars reveals their involvement in ABA signalling.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {329}, pmid = {30514219}, issn = {1471-2229}, support = {2015BAD15B01//national key technology R&D program of china/ ; 1630052016004//the Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences/ ; }, mesh = {Abscisic Acid/*metabolism ; Arabidopsis/genetics ; Dehydration/metabolism ; Genome, Plant/genetics ; Genome-Wide Association Study ; Glutaredoxins/genetics/*metabolism/physiology ; Manihot/genetics/*metabolism/physiology ; Phylogeny ; Plant Growth Regulators/*metabolism ; Plant Leaves/metabolism ; Plant Proteins/genetics/*metabolism/physiology ; Sequence Alignment ; Signal Transduction/genetics ; }, abstract = {BACKGROUND: CC-type glutaredoxins (GRXs) are plant-specific glutaredoxin, play regulatory roles in response of biotic and abiotic stress. However, it is not clear whether the CC-type GRXs are involve in drought response in cassava (Manihot esculenta), an important tropical tuber root crop.

RESULTS: Herein, genome-wide analysis identified 18 CC-type GRXs in the cassava genome, of which six (namely MeGRXC3, C4, C7, C14, C15, and C18) were induced by drought stress in leaves of two cassava cultivars Argentina 7 (Arg7) and South China 124 (SC124). Exogenous abscisic acid (ABA) application induced the expression of all the six CC-type GRXs in leaves of both Arg7 and SC124 plants. Overexpression of MeGRXC15 in Arabidopsis (Col-0) increases tolerance of ABA on the sealed agar plates, but results in drought hypersensitivity in soil-grown plants. The results of microarray assays show that MeGRXC15 overexpression affected the expression of a set of transcription factors which involve in stress response, ABA, and JA/ET signalling pathway. The results of protein interaction analysis show that MeGRXC15 can interact with TGA5 from Arabidopsis and MeTGA074 from cassava.

CONCLUSIONS: CC-type glutaredoxins play regulatory roles in cassava response to drought possibly through ABA signalling pathway.}, } @article {pmid30514218, year = {2018}, author = {Ding, Y and Wang, Z and Ren, M and Zhang, P and Li, Z and Chen, S and Ge, C and Wang, Y}, title = {Iron and callose homeostatic regulation in rice roots under low phosphorus.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {326}, pmid = {30514218}, issn = {1471-2229}, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; Glucans/*metabolism ; Homeostasis ; Iron/*metabolism ; Oryza/growth & development/*metabolism ; Phosphorus/*deficiency/metabolism ; Plant Roots/growth & development/*metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Phosphorus (Pi) deficiency induces root morphological remodeling in plants. The primary root length of rice increased under Pi deficiency stress; however, the underlying mechanism is not well understood. In this study, transcriptome analysis (RNA-seq) and Real-time quantitative PCR (qRT-PCR) techniques were combined with the determination of physiological and biochemical indexes to research the regulation mechanisms of iron (Fe) accumulation and callose deposition in rice roots, to illuminate the relationship between Fe accumulation and primary root growth under Pi deficient conditions.

RESULTS: Induced expression of LPR1 genes was observed under low Pi, which also caused Fe accumulation, resulting in iron plaque formation on the root surface in rice; however, in contrast to Arabidopsis, low Pi promoted primary root lengthening in rice. This might be due to Fe accumulation and callose deposition being still appropriately regulated under low Pi. The down-regulated expression of Fe-uptake-related key genes (including IRT, NAS, NAAT, YSLs, OsNRAMP1, ZIPs, ARF, and Rabs) inhibited iron uptake pathways I, II, and III in rice roots under low Pi conditions. In contrast, due to the up-regulated expression of the VITs gene, Fe was increasingly stored in both root vacuoles and cell walls. Furthermore, due to induced expression and increased activity of β-1-3 glucanase, callose deposition was more controlled in low Pi treated rice roots. In addition, low Pi and low Fe treatment still caused primary root lengthening.

CONCLUSIONS: The obtained results indicate that Low phosphorus induces iron and callose homeostatic regulation in rice roots. Because of the Fe homeostatic regulation, Fe plays a small role in rice root morphological remodeling under low Pi.}, } @article {pmid30514213, year = {2018}, author = {Orts, F and Ten Have, A}, title = {Structure-function analysis of Sedolisins: evolution of tripeptidyl peptidase and endopeptidase subfamilies in fungi.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {464}, pmid = {30514213}, issn = {1471-2105}, support = {PICT2013-2296//Fondo para la Investigación Científica y Tecnológica/ ; }, mesh = {Amino Acid Sequence ; Aminopeptidases/*metabolism ; Carboxypeptidases/*metabolism ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/*metabolism ; Fungi/*metabolism ; Phylogeny ; Serine Endopeptidases/*metabolism ; }, abstract = {BACKGROUND: Sedolisins are acid proteases that are related to the basic subtilisins. They have been identified in all three superkingdoms but are not ubiquitous, although fungi that secrete acids as part of their lifestyle can have up to six paralogs. Both TriPeptidyl Peptidase (TPP) and endopeptidase activity have been identified and it has been suggested that these correspond to separate subfamilies.

RESULTS: We studied eukaryotic sedolisins by computational analysis. A maximum likelihood tree shows one major clade containing non-fungal sequences only and two major as well as two minor clades containing only fungal sequences. One of the major fungal clades contains all known TPPs whereas the other contains characterized endosedolisins. We identified four Cluster Specific Inserts (CSIs) in endosedolisins, of which CSIs 1, 3 and 4 appear as solvent exposed according to structure modeling. Part of CSI2 is exposed but a short stretch forms a novel and partially buried α-helix that induces a conformational change near the binding pocket. We also identified a total of 15 specificity determining positions (SDPs) of which five, identified in two independent analyses, form highly connected SDP sub-networks. Modeling of virtual mutants suggests a key role for the W307A or F307A substitution. The remaining four key SDPs physically interact at the interface of the catalytic domain and the enzyme's prosegment. Modeling of virtual mutants suggests these SDPs are indeed required to compensate the conformational change induced by CSI2 and the A307. One of the two small fungal clades concerns a subfamily that contains 213 sequences, is mostly similar to the major TPP subfamily but differs, interestingly, in position 307, showing mostly isoleucine and threonine.

CONCLUSIONS: Analysis confirms there are at least two sedolisin subfamilies in fungi: TPPs and endopeptidases, and suggests a third subfamily with unknown characteristics. Sequence and functional diversification was centered around buried SDP307 and resulted in a conformational change of the pocket. Mutual Information network analysis forms a useful instrument in the corroboration of predicted SDPs.}, } @article {pmid30514212, year = {2018}, author = {Natali, L and Vangelisti, A and Guidi, L and Remorini, D and Cotrozzi, L and Lorenzini, G and Nali, C and Pellegrini, E and Trivellini, A and Vernieri, P and Landi, M and Cavallini, A and Giordani, T}, title = {How Quercus ilex L. saplings face combined salt and ozone stress: a transcriptome analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {872}, pmid = {30514212}, issn = {1471-2164}, support = {PRA2015//Università di Pisa/ ; }, abstract = {BACKGROUND: Similar to other urban trees, holm oaks (Quercus ilex L.) provide a physiological, ecological and social service in the urban environment, since they remove atmospheric pollution. However, the urban environment has several abiotic factors that negatively influence plant life, which are further exacerbated due to climate change, especially in the Mediterranean area. Among these abiotic factors, increased uptake of Na + and Cl - usually occurs in trees in the urban ecosystem; moreover, an excess of the tropospheric ozone concentration in Mediterranean cities further affects plant growth and survival. Here, we produced and annotated a de novo leaf transcriptome of Q. ilex as well as transcripts over- or under-expressed after a single episode of O3 (80 nl l-1, 5 h), a salt treatment (150 mM for 15 days) or a combination of these treatments, mimicking a situation that plants commonly face, especially in urban environments.

RESULTS: Salinity dramatically changed the profile of expressed transcripts, while the short O3 pulse had less effect on the transcript profile. However, the short O3 pulse had a very strong effect in inducing over- or under-expression of some genes in plants coping with soil salinity. Many differentially regulated genes were related to stress sensing and signalling, cell wall remodelling, ROS sensing and scavenging, photosynthesis and to sugar and lipid metabolism. Most differentially expressed transcripts revealed here are in accordance with a previous report on Q. ilex at the physiological and biochemical levels, even though the expression profiles were overall more striking than those found at the biochemical and physiological levels.

CONCLUSIONS: We produced for the first time a reference transcriptome for Q. ilex, and performed gene expression analysis for this species when subjected to salt, ozone and a combination of the two. The comparison of gene expression between the combined salt + ozone treatment and salt or ozone alone showed that even though many differentially expressed genes overlap all treatments, combined stress triggered a unique response in terms of gene expression modification. The obtained results represent a useful tool for studies aiming to investigate the effects of environmental stresses in urban-adapted tree species.}, } @article {pmid30514211, year = {2018}, author = {Prazsák, I and Moldován, N and Balázs, Z and Tombácz, D and Megyeri, K and Szűcs, A and Csabai, Z and Boldogkői, Z}, title = {Long-read sequencing uncovers a complex transcriptome topology in varicella zoster virus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {873}, pmid = {30514211}, issn = {1471-2164}, abstract = {BACKGROUND: Varicella zoster virus (VZV) is a human pathogenic alphaherpesvirus harboring a relatively large DNA molecule. The VZV transcriptome has already been analyzed by microarray and short-read sequencing analyses. However, both approaches have substantial limitations when used for structural characterization of transcript isoforms, even if supplemented with primer extension or other techniques. Among others, they are inefficient in distinguishing between embedded RNA molecules, transcript isoforms, including splice and length variants, as well as between alternative polycistronic transcripts. It has been demonstrated in several studies that long-read sequencing is able to circumvent these problems.

RESULTS: In this work, we report the analysis of the VZV lytic transcriptome using the Oxford Nanopore Technologies sequencing platform. These investigations have led to the identification of 114 novel transcripts, including mRNAs, non-coding RNAs, polycistronic RNAs and complex transcripts, as well as 10 novel spliced transcripts and 25 novel transcription start site isoforms and transcription end site isoforms. A novel class of transcripts, the nroRNAs are described in this study. These transcripts are encoded by the genomic region located in close vicinity to the viral replication origin. We also show that the ORF63 exhibits a complex structural variation encompassing the splice sites of VZV latency transcripts. Additionally, we have detected RNA editing in a novel non-coding RNA molecule.

CONCLUSIONS: Our investigations disclosed a composite transcriptomic architecture of VZV, including the discovery of novel RNA molecules and transcript isoforms, as well as a complex meshwork of transcriptional read-throughs and overlaps. The results represent a substantial advance in the annotation of the VZV transcriptome and in understanding the molecular biology of the herpesviruses in general.}, } @article {pmid30514210, year = {2018}, author = {Panara, F and Lopez, L and Daddiego, L and Fantini, E and Facella, P and Perrotta, G}, title = {Comparative transcriptomics between high and low rubber producing Taraxacum kok-saghyz R. plants.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {875}, pmid = {30514210}, issn = {1471-2164}, abstract = {BACKGROUND: Taraxacum kok-saghyz R. (Tks) is a promising alternative species to Hevea brasiliensis for production of high quality natural rubber (NR). A comparative transcriptome analysis of plants with differential production of NR will contribute to elucidate which genes are involved in the synthesis, regulation and accumulation of this natural polymer and could help to develop Tks into a rubber crop.

RESULTS: We measured rubber content in the latex of 90 individual Tks plants from 9 accessions, observing a high degree of variability. We carried out de novo root transcriptome sequencing, assembly, annotation and comparison of gene expression of plants with the lower (LR plants) and the higher rubber content (HR plants). The transcriptome analysis also included one plant that did not expel latex, in principle depleted of latex transcripts. Moreover, the transcription of some genes well known to play a major role in rubber biosynthesis, was probed by qRT-PCR. Our analysis showed a high modulation of genes involved in the synthesis of NR between LR and HR plants, and evidenced that genes involved in sesquiterpenoids, monoterpenoids and phenylpropanoid biosynthesis are upregulated in LR plants.

CONCLUSIONS: Our results show that a higher amount of rubber in the latex in HR plants is positively correlated with high expression levels of a number of genes directly involved in rubber synthesis showing that NR production is highly controlled at transcriptional level. On the other hand, lower amounts of rubber in LR plants is related with higher expression of genes involved in the synthesis of other secondary metabolites that, we hypothesize, may compete towards NR biosynthesis. This dataset represents a fundamental genomic resource for the study of Tks and the comprehension of the synthesis of NR and other biochemically and pharmacologically relevant compounds in the Taraxacum genus.}, } @article {pmid30514209, year = {2018}, author = {Rumore, J and Tschetter, L and Kearney, A and Kandar, R and McCormick, R and Walker, M and Peterson, CL and Reimer, A and Nadon, C}, title = {Evaluation of whole-genome sequencing for outbreak detection of Verotoxigenic Escherichia coli O157:H7 from the Canadian perspective.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {870}, pmid = {30514209}, issn = {1471-2164}, abstract = {BACKGROUND: Rapid and accurate identification of Verotoxigenic Escherichia coli (VTEC) O157:H7 is dependent on well-established, standardized and highly discriminatory typing methods. Currently, conventional subtyping tests for foodborne bacterial pathogen surveillance are rapidly being replaced with whole-genome sequencing (WGS) in public health laboratories. The capacity of WGS to revolutionize global foodborne disease surveillance has positioned this tool to become the new gold standard; however, to ensure evidence standards for public health decision making can still be achieved, the performance of WGS must be thoroughly validated against current gold standard methods prior to implementation. Here we aim to verify the performance of WGS in comparison to pulsed-field gel electrophoresis (PFGE) and multiple-locus variable-number tandem repeat analysis (MLVA) for eight retrospective outbreaks of VTEC O157:H7 from the Canadian perspective. Since real-time implementation and routine use of WGS in public health laboratories is highly reliant on standardized data analysis tools, we also provide a comparative analysis of two popular methodologies for WGS analyses; an in-house developed single nucleotide variant phylogenomics (SNVPhyl) pipeline and the BioNumerics whole genome multilocus sequence typing (wgMLST) tool. To provide a useful and consistent starting point for examining laboratory-based surveillance data for VTEC O157:H7 in Canada, we also aim to describe the number of genetic differences observed among outbreak-associated isolates.

RESULTS: WGS provided enhanced resolution over traditional subtyping methods, and accurately distinguished outbreak-related isolates from non-outbreak related isolates with high epidemiological concordance. WGS also illuminated potential linkages between sporadic cases of illness and contaminated food, and isolates spanning multiple years. The topologies generated by SNVPhyl and wgMLST were highly congruent with strong statistical support. Few genetic differences were observed among outbreak-related isolates (≤5 SNVs/ < 10 wgMLST alleles) unless the outbreak was suspected to be multi-strain.

CONCLUSIONS: This study validates the superiority of WGS and indicates the BioNumerics wgMLST schema is suitable for surveillance and cluster detection of VTEC O157:H7. These findings will provide a useful and consistent starting point for examining WGS data for prospective laboratory-based surveillance of VTEC O157:H7, but however, the data will continue to be interpreted according to context and in combination with epidemiological and food safety evidence to inform public-health decision making in Canada.}, } @article {pmid30514207, year = {2018}, author = {Štorchová, H and Stone, JD and Sloan, DB and Abeyawardana, OAJ and Müller, K and Walterová, J and Pažoutová, M}, title = {Homologous recombination changes the context of Cytochrome b transcription in the mitochondrial genome of Silene vulgaris KRA.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {874}, pmid = {30514207}, issn = {1471-2164}, support = {16-09220S//Grantová Agentura České Republiky/ ; MCB-1733227//National Science Foundation/ ; . CZ.02.1.01/0.0/0.0/16_019/0000738//European Regional Development Fund/ ; }, abstract = {BACKGROUND: Silene vulgaris (bladder campion) is a gynodioecious species existing as two genders - male-sterile females and hermaphrodites. Cytoplasmic male sterility (CMS) is generally encoded by mitochondrial genes, which interact with nuclear fertility restorer genes. Mitochondrial genomes of this species vary in DNA sequence, gene order and gene content. Multiple CMS genes are expected to exist in S. vulgaris, but little is known about their molecular identity.

RESULTS: We assembled the complete mitochondrial genome from the haplotype KRA of S. vulgaris. It consists of five chromosomes, two of which recombine with each other. Two small non-recombining chromosomes exist in linear, supercoiled and relaxed circle forms. We compared the mitochondrial transcriptomes from females and hermaphrodites and confirmed the differentially expressed chimeric gene bobt as the strongest CMS candidate gene in S. vulgaris KRA. The chimeric gene bobt is co-transcribed with the Cytochrome b (cob) gene in some genomic configurations. The co-transcription of a CMS factor with an essential gene may constrain transcription inhibition as a mechanism for fertility restoration because of the need to maintain appropriate production of the necessary protein. Homologous recombination places the gene cob outside the control of bobt, which allows for the suppression of the CMS gene by the fertility restorer genes. We found the loss of three editing sites in the KRA mitochondrial genome and identified four sites with highly distinct editing rates between KRA and another S. vulgaris haplotypes (KOV). Three of these highly differentially edited sites were located in the transport membrane protein B (mttB) gene. They resulted in differences in MttB protein sequences between haplotypes.

CONCLUSIONS: Frequent homologous recombination events that are widespread in plant mitochondrial genomes may change chromosomal configurations and also the control of gene transcription including CMS gene expression. Posttranscriptional processes, e.g. RNA editing shall be evaluated in evolutionary and co-evolutionary studies of mitochondrial genes, because they may change protein composition despite the sequence identity of the respective genes. The investigation of natural populations of wild species such as S. vulgaris are necessary to reveal important aspects of CMS missed in domesticated crops, the traditional focus of the CMS studies.}, } @article {pmid30514206, year = {2018}, author = {Yu, S and Zheng, C and Zhou, F and Baillie, DL and Rose, AM and Deng, Z and Chu, JS}, title = {Genomic identification and functional analysis of essential genes in Caenorhabditis elegans.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {871}, pmid = {30514206}, issn = {1471-2164}, support = {289473//Canadian Institutes of Health Research/Canada ; RGPIN - 2015 - 04266//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {BACKGROUND: Essential genes are required for an organism's viability and their functions can vary greatly, spreading across many pathways. Due to the importance of essential genes, large scale efforts have been undertaken to identify the complete set of essential genes and to understand their function. Studies of genome architecture and organization have found that genes are not randomly disturbed in the genome.

RESULTS: Using combined genetic mapping, Illumina sequencing, and bioinformatics analyses, we successfully identified 44 essential genes with 130 lethal mutations in genomic regions of C. elegans of around 7.3 Mb from Chromosome I (left). Of the 44 essential genes, six of which were genes not characterized previously by mutant alleles, let-633/let-638 (B0261.1), let-128 (C53H9.2), let-511 (W09C3.4), let-162 (Y47G6A.18), let-510 (Y47G6A.19), and let-131 (Y71G12B.6). Examine essential genes with Hi-C data shows that essential genes tend to cluster within TAD units rather near TAD boundaries. We have also shown that essential genes in the left half of chromosome I in C. elegans function in enzyme and nucleic acid binding activities during fundamental processes, such as DNA replication, transcription, and translation. From protein-protein interaction networks, essential genes exhibit more protein connectivity than non-essential genes in the genome. Also, many of the essential genes show strong expression in embryos or early larvae stages, indicating that they are important to early development.

CONCLUSIONS: Our results confirmed that this work provided a more comprehensive picture of the essential gene and their functional characterization. These genetic resources will offer important tools for further heath and disease research.}, } @article {pmid30514205, year = {2018}, author = {Karlsen, E and Schulz, C and Almaas, E}, title = {Automated generation of genome-scale metabolic draft reconstructions based on KEGG.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {467}, pmid = {30514205}, issn = {1471-2105}, support = {269084//Norges Forskningsråd (NO)/ ; 271585//Norges Forskningsråd/ ; }, mesh = {Computational Biology/*methods ; Databases, Genetic ; Genome/*genetics ; Metabolic Networks and Pathways/*genetics ; Molecular Sequence Annotation ; }, abstract = {BACKGROUND: Constraint-based modeling is a widely used and powerful methodology to assess the metabolic phenotypes and capabilities of an organism. The starting point and cornerstone of all such modeling is a genome-scale metabolic network reconstruction. The creation, further development, and application of such networks is a growing field of research thanks to a plethora of readily accessible computational tools. While the majority of studies are focused on single-species analyses, typically of a microbe, the computational study of communities of organisms is gaining attention. Similarly, reconstructions that are unified for a multi-cellular organism have gained in popularity. Consequently, the rapid generation of genome-scale metabolic reconstructed networks is crucial. While multiple web-based or stand-alone tools are available for automated network reconstruction, there is, however, currently no publicly available tool that allows the swift assembly of draft reconstructions of community metabolic networks and consolidated metabolic networks for a specified list of organisms.

RESULTS: Here, we present AutoKEGGRec, an automated tool that creates first draft metabolic network reconstructions of single organisms, community reconstructions based on a list of organisms, and finally a consolidated reconstruction for a list of organisms or strains. AutoKEGGRec is developed in Matlab and works seamlessly with the COBRA Toolbox v3, and it is based on only using the KEGG database as external input. The generated first draft reconstructions are stored in SBML files and consist of all reactions for a KEGG organism ID and corresponding linked genes. This provides a comprehensive starting point for further refinement and curation using the host of COBRA toolbox functions or other preferred tools. Through the data structures created, the tool also facilitates a comparative analysis of metabolic content in any given number of organisms present in the KEGG database.

CONCLUSION: AutoKEGGRec provides a first step in a metabolic network reconstruction process, filling a gap for tools creating community and consolidated metabolic networks. Based only on KEGG data as external input, the generated reconstructions consist of data with a directly traceable foundation and pedigree. With AutoKEGGRec, this kind of modeling is made accessible to a wider part of the genome-scale metabolic analysis community.}, } @article {pmid30514204, year = {2018}, author = {Tolvanen, J and Seppänen, JT and Mönkkönen, M and Thomson, RL and Ylönen, H and Forsman, JT}, title = {Interspecific information on predation risk affects nest site choice in a passerine bird.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {181}, pmid = {30514204}, issn = {1471-2148}, mesh = {Animals ; Breeding ; *Choice Behavior ; Cues ; Female ; Nesting Behavior/*physiology ; Predatory Behavior/*physiology ; Risk Factors ; Songbirds/*physiology ; Species Specificity ; }, abstract = {BACKGROUND: Breeding site choice constitutes an important part of the species niche. Nest predation affects breeding site choice, and has been suggested to drive niche segregation and local coexistence of species. Interspecific social information use may, in turn, result in copying or rejection of heterospecific niche characteristics and thus affect realized niche overlap between species. We tested experimentally whether a migratory bird, the pied flycatcher Ficedula hypoleuca, collects information about nest predation risk from indirect cues of predators visiting nests of heterospecific birds. Furthermore, we investigated whether the migratory birds can associate such information with a specific nest site characteristic and generalize the information to their own nest site choice.

RESULTS: Our results demonstrate that flycatchers can use the fate of heterospecific nesting attempts in their own nest site choice, but do so selectively. Young flycatcher females, when making the decision quickly, associated the fate of an artificial nest with nest-site characteristics and avoided the characteristic associated with higher nest predation risk.

CONCLUSIONS: Copying nest site choices of successful heterospecifics, and avoiding choices which led to failed attempts, may amplify or counter effects of nest predation on niche overlap, with important consequences for between-species niche divergence-convergence dynamics, species coexistence and predator-prey interactions.}, } @article {pmid30514203, year = {2018}, author = {Ma, KY and van Herwerden, L and Newman, SJ and Berumen, ML and Choat, JH and Chu, KH and Sadovy de Mitcheson, Y}, title = {Contrasting population genetic structure in three aggregating groupers (Percoidei: Epinephelidae) in the Indo-West Pacific: the importance of reproductive mode.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {180}, pmid = {30514203}, issn = {1471-2148}, mesh = {Animals ; Genetics, Population ; Microsatellite Repeats/genetics ; Pacific Ocean ; Perciformes/classification/*genetics/*physiology ; Phylogeny ; Phylogeography ; Reproduction/*genetics ; }, abstract = {BACKGROUND: Understanding the factors shaping population genetic structure is important for evolutionary considerations as well as for management and conservation. While studies have revealed the importance of palaeogeographic changes in shaping phylogeographic patterns in multiple marine fauna, the role of reproductive behaviour is rarely considered in reef fishes. We investigated the population genetics of three commercially important aggregating grouper species in the Indo-West Pacific, namely the camouflage grouper Epinephelus polyphekadion, the squaretail coral grouper Plectropomus areolatus, and the common coral trout P. leopardus, with similar life histories but distinct spatio-temporal characteristics in their patterns of forming spawning aggregations.

RESULTS: By examining their mitochondrial control region and 9-11 microsatellite markers, we found an overarching influence of palaeogeographic events in the population structure of all species, with genetic breaks largely coinciding with major biogeographic barriers. The divergence time of major lineages in these species coincide with the Pleistocene glaciations. Higher connectivity is evident in E. polyphekadion and P. areolatus that assemble in larger numbers at fewer spawning aggregations and in distinctive offshore locations than in P. leopardus which has multiple small, shelf platform aggregations.

CONCLUSIONS: While palaeogeographic events played an important role in shaping the population structure of the target species, the disparity in population connectivity detected may be partly attributable to differences in their reproductive behaviour, highlighting the need for more investigations on this characteristic and the need to consider reproductive mode in studies of connectivity and population genetics.}, } @article {pmid30514202, year = {2018}, author = {Ren, Y and Ay, A and Kahveci, T}, title = {Shortest path counting in probabilistic biological networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {465}, pmid = {30514202}, issn = {1471-2105}, support = {DBI-1262451//Directorate for Biological Sciences/ ; }, mesh = {Biological Products/*metabolism ; Gene Regulatory Networks/*genetics ; Humans ; }, abstract = {BACKGROUND: Biological regulatory networks, representing the interactions between genes and their products, control almost every biological activity in the cell. Shortest path search is critical to apprehend the structure of these networks, and to detect their key components. Counting the number of shortest paths between pairs of genes in biological networks is a polynomial time problem. The fact that biological interactions are uncertain events however drastically complicates the problem, as it makes the topology of a given network uncertain.

RESULTS: In this paper, we develop a novel method to count the number of shortest paths between two nodes in probabilistic networks. Unlike earlier approaches, which uses the shortest path counting methods that are specifically designed for deterministic networks, our method builds a new mathematical model to express and compute the number of shortest paths. We prove the correctness of this model.

CONCLUSIONS: We compare our novel method to three existing shortest path counting methods on synthetic and real gene regulatory networks. Our experiments demonstrate that our method is scalable, and it outperforms the existing methods in accuracy. Application of our shortest path counting method to detect communities in probabilistic networks shows that our method successfully finds communities in probabilistic networks. Moreover, our experiments on cell cycle pathway among different cancer types exhibit that our method helps in uncovering key functional characteristics of biological networks.}, } @article {pmid30514201, year = {2018}, author = {Herry, F and Hérault, F and Picard Druet, D and Varenne, A and Burlot, T and Le Roy, P and Allais, S}, title = {Design of low density SNP chips for genotype imputation in layer chicken.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {108}, pmid = {30514201}, issn = {1471-2156}, abstract = {BACKGROUND: The main goal of selection is to achieve genetic gain for a population by choosing the best breeders among a set of selection candidates. Since 2013, the use of a high density genotyping chip (600K Affymetrix® Axiom® HD genotyping array) for chicken has enabled the implementation of genomic selection in layer and broiler breeding, but the genotyping costs remain high for a routine use on a large number of selection candidates. It has thus been deemed interesting to develop a low density genotyping chip that would induce lower costs. In this perspective, various simulation studies have been conducted to find the best way to select a set of SNPs for low density genotyping of two laying hen lines.

RESULTS: To design low density SNP chips, two methodologies, based on equidistance (EQ) or on linkage disequilibrium (LD) were compared. Imputation accuracy was assessed as the mean correlation between true and imputed genotypes. The results showed correlations more sensitive to false imputation of SNPs having low Minor Allele Frequency (MAF) when the EQ methodology was used. An increase in imputation accuracy was obtained when SNP density was increased, either through an increase in the number of selected windows on a chromosome or through the rise of the LD threshold. Moreover, the results varied depending on the type of chromosome (macro or micro-chromosome). The LD methodology enabled to optimize the number of SNPs, by reducing the SNP density on macro-chromosomes and by increasing it on micro-chromosomes. Imputation accuracy also increased when the size of the reference population was increased. Conversely, imputation accuracy decreased when the degree of kinship between reference and candidate populations was reduced. Finally, adding selection candidates' dams in the reference population, in addition to their sire, enabled to get better imputation results.

CONCLUSIONS: Whichever the SNP chip, the methodology, and the scenario studied, highly accurate imputations were obtained, with mean correlations higher than 0.83. The key point to achieve good imputation results is to take into account chicken lines' LD when designing a low density SNP chip, and to include the candidates' direct parents in the reference population.}, } @article {pmid30514200, year = {2018}, author = {McDougall, C and Hammond, MJ and Dailey, SC and Somorjai, IML and Cummins, SF and Degnan, BM}, title = {The evolution of ependymin-related proteins.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {182}, pmid = {30514200}, issn = {1471-2148}, support = {204821/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Eukaryota/genetics ; Eukaryotic Cells/metabolism ; *Evolution, Molecular ; Gene Duplication ; Models, Molecular ; Nerve Tissue Proteins/chemistry/*genetics ; Phylogeny ; }, abstract = {BACKGROUND: Ependymins were originally defined as fish-specific secreted glycoproteins involved in central nervous system plasticity and memory formation. Subsequent research revealed that these proteins represent a fish-specific lineage of a larger ependymin-related protein family (EPDRs). EPDRs have now been identified in a number of bilaterian animals and have been implicated in diverse non-neural functions. The recent discoveries of putative EPDRs in unicellular holozoans and an expanded EPDR family with potential roles in conspecific communication in crown-of-thorns starfish suggest that the distribution and diversity of EPDRs is significantly broader than currently understood.

RESULTS: We undertook a systematic survey to determine the distribution and evolution of EPDRs in eukaryotes. In addition to Bilateria, EPDR genes were identified in Cnidaria, Placozoa, Porifera, Choanoflagellatea, Filasterea, Apusozoa, Amoebozoa, Charophyta and Percolozoa, and tentatively in Cercozoa and the orphan group Malawimonadidae. EPDRs appear to be absent from prokaryotes and many eukaryote groups including ecdysozoans, fungi, stramenopiles, alveolates, haptistans and cryptistans. The EPDR family can be divided into two major clades and has undergone lineage-specific expansions in a number of metazoan lineages, including in poriferans, molluscs and cephalochordates. Variation in a core set of conserved residues in EPDRs reveals the presence of three distinct protein types; however, 3D modelling predicts overall protein structures to be similar.

CONCLUSIONS: Our results reveal an early eukaryotic origin of the EPDR gene family and a dynamic pattern of gene duplication and gene loss in animals. This research provides a phylogenetic framework for the analysis of the functional evolution of this gene family.}, } @article {pmid30513341, year = {2019}, author = {Hadifar, S and Shamkhali, L and Kargarpour Kamakoli, M and Mostafaei, S and Khanipour, S and Mansoori, N and Fateh, A and Siadat, SD and Vaziri, F}, title = {Genetic diversity of Mycobacterium tuberculosis isolates causing pulmonary and extrapulmonary tuberculosis in the capital of Iran.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {46-52}, doi = {10.1016/j.ympev.2018.11.019}, pmid = {30513341}, issn = {1095-9513}, abstract = {OBJECTIVES: Evaluation of the genetic diversity of Mycobacterium tuberculosis (M.tb) and determining if the association between a specific genotype and the site of infection is crucial. Accordingly, the current study aimed at comparing predominant M.tb genotypes in pulmonary (PTB) and extrapulmonary tuberculosis (EPTB) isolates circulating in the capital of Iran.

METHODS: The genetic diversity of culture-confirmed PTB and EPTB isolates were evaluated by Spoligotyping and MIRU-VNTR (mycobacterial interspersed repetitive-unit-variable-number tandem-repeat) typing methods. Genotyping data were analyzed with SITVIT, MIRU-VNTRplus, and TBminer databases. To assess adjusted associations, chi-square/the Fisher exact test and multiple logistic regression model were applied.

RESULTS: URAL2 (NEW-1) (28/88; 31.8%) and CAS1-DELHI (25/84; 29.8%) genotypes were predominant in EPTB and PTB strains, respectively. Based on MIRU-VNTR typing, 158 different MIRU-VNTR patterns were identified. Clustering rate and minimum estimate of the proportion of TB caused by recent transmission was 4.1% and 8.1%, respectively.

CONCLUSIONS: The current study provided new insight into circulating genotypes of M.tb in PTB and EPTB patients in Tehran, Iran. This low percentage of TB transmission rate, demonstrated that mode of TB transmission was mainly associated with reactivation of latent TB rather than recently transmitted infection in this region. There was no significant difference in the association between the genotypes of M.tb strains and the site of the disease.}, } @article {pmid30513340, year = {2019}, author = {Jiang, XL and Gardner, EM and Meng, HH and Deng, M and Xu, GB}, title = {Land bridges in the Pleistocene contributed to flora assembly on the continental islands of South China: Insights from the evolutionary history of Quercus championii.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {36-45}, doi = {10.1016/j.ympev.2018.11.021}, pmid = {30513340}, issn = {1095-9513}, abstract = {The South China Mainland (SCM) and its adjacent continental islands are a global biodiversity hotspot. However, how and when plants dispersed between SCM and Hainan/Taiwan Islands remains largely unknown. In this study, we used restriction site-associated DNA sequencing (RAD-seq) to identify the demographic dynamics and local adaptation of Quercus championii, a dominant forests tree distributed in SCM and Hainan/Taiwan Islands. Through phylogenetic reconstruction, principal components analysis (PCA) and structure analysis, we identified four distinct Q. championii lineages that correspond to its geographical distribution. The genetic structure of Hainan Island population was distinct, possibly reflecting an introgression. We conducted an approximate Bayesian computation analyses and found that Q. championii originated from Southwest China-Northern Vietnam, then dispersed to Southeast China as the climate warmed. During the Pleistocene glacial period, land bridges arose between SCM and Hainan/Taiwan Islands, and the land bridges likely facilitated species dispersal from SCM to these islands. We found a strong correlation between genetic variation and isothermality through a gradient forest analysis and identified precipitation seasonality as a key driver to the local adaptation of Q. championii. Finally, we analyzed putative adaptation loci and identified genes regulating vegetative and reproductive organ development as important for the adaptation of Q. championii to heterogeneous environments. We provide new insights into the evolutionary history and local adaptation of biotas in Southern China and adjacent islands.}, } @article {pmid30513308, year = {2019}, author = {Baker, NE and Kiparaki, M and Khan, C}, title = {A potential link between p53, cell competition and ribosomopathy in mammals and in Drosophila.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {17-19}, doi = {10.1016/j.ydbio.2018.11.018}, pmid = {30513308}, issn = {1095-564X}, abstract = {The term cell competition has been used to describe the phenomenon whereby particular cells can be eliminated during tissue growth only when more competitive cells are available to replace them. Multiple examples implicate differential activity of p53 in cell competition in mammals, but p53 has not been found to have the same role in Drosophila, where the phenomenon of cell competition was first recognized. Recent studies now show that Drosophila cells harboring mutations in Ribosomal protein (Rp) genes, which are eliminated by cell competition with wild type cells, activate a p53 target gene, Xrp1. In Diamond Blackfan Anemia, human Rp mutants activate p53 itself, through a nucleolar stress pathway. These results suggest a link between mammalian and Drosophila Rp mutants, translation, and cell competition.}, } @article {pmid30511915, year = {2019}, author = {Tuo, L and Yan, XR and Li, FN and Yang, C and An, MB and Sun, CH}, title = {Amnibacterium flavum sp. nov., a novel endophytic actinobacterium isolated from bark of Nerium indicum Mill.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {285-290}, doi = {10.1099/ijsem.0.003156}, pmid = {30511915}, issn = {1466-5034}, abstract = {A Gram-stain-positive, aerobic, short-rod-shaped, non-spore-forming actinobacterial strain, designated M8JJ-5T, was isolated from a surface-sterilized bark of Neriumindicum Mill. collected from Guizhou, China, and investigated by a polyphasic approach to determine its taxonomic position. Strain M8JJ-5T grew optimally without NaCl at 28 °C and at pH 7.0-8.0. Substrate mycelia and aerial mycelia were not formed, and no diffusible pigments were observed on the media tested. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain M8JJ-5T was most closely related to the type strains of genus Amnibacterium, and shared highest 16S rRNA gene sequence similarity of 97.29 % to Amnibacterium kyonggiense KSL51201-037T. The DNA G+C content of strain M8JJ-5T was 68.6 mol%. The cell-wall peptidoglycan contained l-2,4-diaminobutyric acid and MK-12, MK-11 were the major menaquinones. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified glycolipid, an unidentified phospholipid and an unidentified lipid, while the major fatty acids were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. On the basis of phylogenetic, chemotaxonomic and phenotypic data, strain M8JJ-5T can be characterized to represent a novel species of the genus Amnibacterium, for which the name Amnibacteriumflavum sp. nov. is proposed. The type strain is M8JJ-5T (=KCTC 49089T=CGMCC 1.16390T).}, } @article {pmid30511914, year = {2019}, author = {Fu, Y and Yan, R and Liu, D and Jiang, S and Cui, L and Guo, X and Wang, X and Zhang, J and Xiang, W}, title = {Trinickia diaoshuihuensis sp. nov., a plant growth promoting bacterium isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {291-296}, doi = {10.1099/ijsem.0.003155}, pmid = {30511914}, issn = {1466-5034}, abstract = {A novel Gram-stain-negative, aerobic, rod-shaped plant growth promoting bacterium, NEAU-SY24T, was isolated from soil in Diaoshuihu, Heilongjiang, China. The isolate grew at temperatures 10-40 °C (optimum, 30 °C), pH 5-8 (optimum, pH 6) and in the presence of up to 1 % (w/v) NaCl, although NaCl was not required for growth. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain NEAU-SY24T belonged to the genus Trinickia and was closely related to Trinickia dabaoshanensis NRRL B-59553T (99.16 % similarity) and Trinickia soli DSM 18235T (99.11 %). The average nucleotide identity values between NEAU-SY24T and its most closely related species were 79.30-87.09 %. The in silico DNA-DNA hybridization values between NEAU-SY24T and T. dabaoshanensis NRRL B-59553T and T. soli DSM 18235T were 29.30 and 24.00 %, respectively, again indicating they belong to different taxa. The genomic DNA G+C content was 63.3 mol%. The major cellular fatty acids were C17 : 0cyclo, C18 : 1ω7c, C16 : 0, summed feature 2 (comprising C14 : 0 3-OH and/or C16 : 1iso I) and C16 : 0 3-OH. The predominant respiratory quinone was Q-8 and the whole-cell sugars contained ribose, glucose and galactose. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine and two unidentified aminolipids. On the basis of morphological, physiological, biochemical and chemotaxonomic analysis, strain NEAU-SY24T was classified as a novel species in the genus Trinickia, for which the name Trinickiadiaoshuihuensis sp. nov. is proposed. The type strain is NEAU-SY24T (=DSM 106065T=CCTCC AA 2018003T).}, } @article {pmid30511202, year = {2018}, author = {Bughio, F and Maggert, KA}, title = {The peculiar genetics of the ribosomal DNA blurs the boundaries of transgenerational epigenetic inheritance.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9591-2}, pmid = {30511202}, issn = {1573-6849}, support = {R01 GM123640/GM/NIGMS NIH HHS/United States ; 1R01GM123640//National Institute of General Medical Sciences/ ; P30CA023074//National Cancer Institute (US)/ ; }, abstract = {Our goal is to draw a line-hypothetical in its totality but experimentally supported at each individual step-connecting the ribosomal DNA and the phenomenon of transgenerational epigenetic inheritance of induced phenotypes. The reasonableness of this hypothesis is offset by its implication, that many (or most) (or all) of the cases of induced-and-inherited phenotypes that are seen to persist for generations are instead unmapped induced polymorphisms in the ribosomal DNA, and thus are the consequence of the peculiar and enduringly fascinating genetics of the highly transcribed repeat DNA structure at that locus.}, } @article {pmid30510241, year = {2019}, author = {Huyghe, JR and Bien, SA and Harrison, TA and Kang, HM and Chen, S and Schmit, SL and Conti, DV and Qu, C and Jeon, J and Edlund, CK and Greenside, P and Wainberg, M and Schumacher, FR and Smith, JD and Levine, DM and Nelson, SC and Sinnott-Armstrong, NA and Albanes, D and Alonso, MH and Anderson, K and Arnau-Collell, C and Arndt, V and Bamia, C and Banbury, BL and Baron, JA and Berndt, SI and Bézieau, S and Bishop, DT and Boehm, J and Boeing, H and Brenner, H and Brezina, S and Buch, S and Buchanan, DD and Burnett-Hartman, A and Butterbach, K and Caan, BJ and Campbell, PT and Carlson, CS and Castellví-Bel, S and Chan, AT and Chang-Claude, J and Chanock, SJ and Chirlaque, MD and Cho, SH and Connolly, CM and Cross, AJ and Cuk, K and Curtis, KR and de la Chapelle, A and Doheny, KF and Duggan, D and Easton, DF and Elias, SG and Elliott, F and English, DR and Feskens, EJM and Figueiredo, JC and Fischer, R and FitzGerald, LM and Forman, D and Gala, M and Gallinger, S and Gauderman, WJ and Giles, GG and Gillanders, E and Gong, J and Goodman, PJ and Grady, WM and Grove, JS and Gsur, A and Gunter, MJ and Haile, RW and Hampe, J and Hampel, H and Harlid, S and Hayes, RB and Hofer, P and Hoffmeister, M and Hopper, JL and Hsu, WL and Huang, WY and Hudson, TJ and Hunter, DJ and Ibañez-Sanz, G and Idos, GE and Ingersoll, R and Jackson, RD and Jacobs, EJ and Jenkins, MA and Joshi, AD and Joshu, CE and Keku, TO and Key, TJ and Kim, HR and Kobayashi, E and Kolonel, LN and Kooperberg, C and Kühn, T and Küry, S and Kweon, SS and Larsson, SC and Laurie, CA and Le Marchand, L and Leal, SM and Lee, SC and Lejbkowicz, F and Lemire, M and Li, CI and Li, L and Lieb, W and Lin, Y and Lindblom, A and Lindor, NM and Ling, H and Louie, TL and Männistö, S and Markowitz, SD and Martín, V and Masala, G and McNeil, CE and Melas, M and Milne, RL and Moreno, L and Murphy, N and Myte, R and Naccarati, A and Newcomb, PA and Offit, K and Ogino, S and Onland-Moret, NC and Pardini, B and Parfrey, PS and Pearlman, R and Perduca, V and Pharoah, PDP and Pinchev, M and Platz, EA and Prentice, RL and Pugh, E and Raskin, L and Rennert, G and Rennert, HS and Riboli, E and Rodríguez-Barranco, M and Romm, J and Sakoda, LC and Schafmayer, C and Schoen, RE and Seminara, D and Shah, M and Shelford, T and Shin, MH and Shulman, K and Sieri, S and Slattery, ML and Southey, MC and Stadler, ZK and Stegmaier, C and Su, YR and Tangen, CM and Thibodeau, SN and Thomas, DC and Thomas, SS and Toland, AE and Trichopoulou, A and Ulrich, CM and Van Den Berg, DJ and van Duijnhoven, FJB and Van Guelpen, B and van Kranen, H and Vijai, J and Visvanathan, K and Vodicka, P and Vodickova, L and Vymetalkova, V and Weigl, K and Weinstein, SJ and White, E and Win, AK and Wolf, CR and Wolk, A and Woods, MO and Wu, AH and Zaidi, SH and Zanke, BW and Zhang, Q and Zheng, W and Scacheri, PC and Potter, JD and Bassik, MC and Kundaje, A and Casey, G and Moreno, V and Abecasis, GR and Nickerson, DA and Gruber, SB and Hsu, L and Peters, U}, title = {Discovery of common and rare genetic risk variants for colorectal cancer.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {76-87}, doi = {10.1038/s41588-018-0286-6}, pmid = {30510241}, issn = {1546-1718}, support = {R01 CA059045/CA/NCI NIH HHS/United States ; R01 CA204279/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; R01 CA160356/CA/NCI NIH HHS/United States ; U01 CA137088/CA/NCI NIH HHS/United States ; U01 CA164930/CA/NCI NIH HHS/United States ; R21 CA191312/CA/NCI NIH HHS/United States ; U01 CA185094/CA/NCI NIH HHS/United States ; R01 CA201407/CA/NCI NIH HHS/United States ; HHSN268201200008I/HL/NHLBI NIH HHS/United States ; U01 CA152756/CA/NCI NIH HHS/United States ; R01 CA193677/CA/NCI NIH HHS/United States ; U19 CA148107/CA/NCI NIH HHS/United States ; }, abstract = {To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 × 10-8, bringing the number of known independent signals for CRC to ~100. New signals implicate lower-frequency variants, Krüppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.}, } @article {pmid30510240, year = {2019}, author = {Seplyarskiy, VB and Akkuratov, EE and Akkuratova, N and Andrianova, MA and Nikolaev, SI and Bazykin, GA and Adameyko, I and Sunyaev, SR}, title = {Error-prone bypass of DNA lesions during lagging-strand replication is a common source of germline and cancer mutations.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {36-41}, doi = {10.1038/s41588-018-0285-7}, pmid = {30510240}, issn = {1546-1718}, support = {R01 MH101244/MH/NIMH NIH HHS/United States ; R35 GM127131/GM/NIGMS NIH HHS/United States ; U01 HG009088/HG/NHGRI NIH HHS/United States ; }, abstract = {Studies in experimental systems have identified a multitude of mutational mechanisms including DNA replication infidelity and DNA damage followed by inefficient repair or replicative bypass. However, the relative contributions of these mechanisms to human germline mutation remain unknown. Here, we show that error-prone damage bypass on the lagging strand plays a major role in human mutagenesis. Transcription-coupled DNA repair removes lesions on the transcribed strand; lesions on the non-transcribed strand are preferentially converted into mutations. In human polymorphism we detect a striking similarity between mutation types predominant on the non-transcribed strand and on the strand lagging during replication. Moreover, damage-induced mutations in cancers accumulate asymmetrically with respect to the direction of replication, suggesting that DNA lesions are resolved asymmetrically. We experimentally demonstrate that replication delay greatly attenuates the mutagenic effect of ultraviolet irradiation, confirming that replication converts DNA damage into mutations. We estimate that at least 10% of human mutations arise due to DNA damage.}, } @article {pmid30510239, year = {2019}, author = {Wang, M and Tu, L and Yuan, D and Zhu, and Shen, C and Li, J and Liu, F and Pei, L and Wang, P and Zhao, G and Ye, Z and Huang, H and Yan, F and Ma, Y and Zhang, L and Liu, M and You, J and Yang, Y and Liu, Z and Huang, F and Li, B and Qiu, P and Zhang, Q and Zhu, L and Jin, S and Yang, X and Min, L and Li, G and Chen, LL and Zheng, H and Lindsey, K and Lin, Z and Udall, JA and Zhang, X}, title = {Reference genome sequences of two cultivated allotetraploid cottons, Gossypium hirsutum and Gossypium barbadense.}, journal = {Nature genetics}, volume = {51}, number = {2}, pages = {224-229}, doi = {10.1038/s41588-018-0282-x}, pmid = {30510239}, issn = {1546-1718}, abstract = {Allotetraploid cotton species (Gossypium hirsutum and Gossypium barbadense) have long been cultivated worldwide for natural renewable textile fibers. The draft genome sequences of both species are available but they are highly fragmented and incomplete1-4. Here we report reference-grade genome assemblies and annotations for G. hirsutum accession Texas Marker-1 (TM-1) and G. barbadense accession 3-79 by integrating single-molecule real-time sequencing, BioNano optical mapping and high-throughput chromosome conformation capture techniques. Compared with previous assembled draft genomes1,3, these genome sequences show considerable improvements in contiguity and completeness for regions with high content of repeats such as centromeres. Comparative genomics analyses identify extensive structural variations that probably occurred after polyploidization, highlighted by large paracentric/pericentric inversions in 14 chromosomes. We constructed an introgression line population to introduce favorable chromosome segments from G. barbadense to G. hirsutum, allowing us to identify 13 quantitative trait loci associated with superior fiber quality. These resources will accelerate evolutionary and functional genomic studies in cotton and inform future breeding programs for fiber improvement.}, } @article {pmid30510238, year = {2019}, author = {Raab, JR and Smith, KN and Spear, CC and Manner, CJ and Calabrese, JM and Magnuson, T}, title = {SWI/SNF remains localized to chromatin in the presence of SCHLAP1.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {26-29}, doi = {10.1038/s41588-018-0272-z}, pmid = {30510238}, issn = {1546-1718}, support = {F32 GM108367/GM/NIGMS NIH HHS/United States ; R01 GM121806/GM/NIGMS NIH HHS/United States ; R01 HD036655/HD/NICHD NIH HHS/United States ; }, abstract = {SCHLAP1 is a long noncoding RNA that is reported to function by depleting the SWI/SNF complex from the genome. We investigated the hypothesis that SCHLAP1 affects only specific compositions of SWI/SNF. Using several assays, we found that SWI/SNF is not depleted from the genome by SCHLAP1 and that SWI/SNF is associated with many coding and noncoding RNAs, suggesting that SCHLAP1 may function in a SWI/SNF-independent manner.}, } @article {pmid30510237, year = {2019}, author = {Hundal, J and Kiwala, S and Feng, YY and Liu, CJ and Govindan, R and Chapman, WC and Uppaluri, R and Swamidass, SJ and Griffith, OL and Mardis, ER and Griffith, M}, title = {Accounting for proximal variants improves neoantigen prediction.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {175-179}, doi = {10.1038/s41588-018-0283-9}, pmid = {30510237}, issn = {1546-1718}, support = {R00 HG007940/HG/NHGRI NIH HHS/United States ; }, abstract = {Recent efforts to design personalized cancer immunotherapies use predicted neoantigens, but most neoantigen prediction strategies do not consider proximal (nearby) variants that alter the peptide sequence and may influence neoantigen binding. We evaluated somatic variants from 430 tumors to understand how proximal somatic and germline alterations change the neoantigenic peptide sequence and also affect neoantigen binding predictions. On average, 241 missense somatic variants were analyzed per sample. Of these somatic variants, 5% had one or more in-phase missense proximal variants. Without incorporating proximal variant correction for major histocompatibility complex class I neoantigen peptides, the overall false discovery rate (incorrect neoantigens predicted) and the false negative rate (strong-binding neoantigens missed) across peptides of lengths 8-11 were estimated as 0.069 (6.9%) and 0.026 (2.6%), respectively.}, } @article {pmid30510236, year = {2019}, author = {Speed, D and Balding, DJ}, title = {SumHer better estimates the SNP heritability of complex traits from summary statistics.}, journal = {Nature genetics}, volume = {51}, number = {2}, pages = {277-284}, doi = {10.1038/s41588-018-0279-5}, pmid = {30510236}, issn = {1546-1718}, abstract = {We present SumHer, software for estimating confounding bias, SNP heritability, enrichments of heritability and genetic correlations using summary statistics from genome-wide association studies. The key difference between SumHer and the existing software LD Score Regression (LDSC) is that SumHer allows the user to specify the heritability model. We apply SumHer to results from 24 large-scale association studies (average sample size 121,000) using our recommended heritability model. We show that these studies tended to substantially over-correct for confounding, and as a result the number of genome-wide significant loci was under-reported by about a quarter. We also estimate enrichments for 24 categories of SNPs defined by functional annotations. A previous study using LDSC reported that conserved regions were 13-fold enriched, and found a further six categories with above threefold enrichment. By contrast, our analysis using SumHer finds that none of the categories have enrichment above twofold. SumHer provides an improved understanding of the genetic architecture of complex traits, which enables more efficient analysis of future genetic data.}, } @article {pmid30510229, year = {2018}, author = {Rumpel, C and Amiraslani, F and Koutika, LS and Smith, P and Whitehead, D and Wollenberg, E}, title = {Put more carbon in soils to meet Paris climate pledges.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {32-34}, doi = {10.1038/d41586-018-07587-4}, pmid = {30510229}, issn = {1476-4687}, } @article {pmid30510228, year = {2018}, author = {Spagnoli, FM}, title = {Location matters for insulin-producing cells.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {50-51}, doi = {10.1038/d41586-018-07490-y}, pmid = {30510228}, issn = {1476-4687}, mesh = {Cell Differentiation ; Family ; Insulin ; Insulin-Secreting Cells ; Insulins ; *Integrins ; *Pancreas ; }, } @article {pmid30510227, year = {2018}, author = {Schnell, DJ}, title = {Exit route evolved into entry path in plants.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {45-46}, doi = {10.1038/d41586-018-07426-6}, pmid = {30510227}, issn = {1476-4687}, } @article {pmid30510226, year = {2018}, author = {Joffin, N and Scherer, PE}, title = {Reduced oxygen consumption by fat cells improves metabolic defects.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {47-48}, doi = {10.1038/d41586-018-07248-6}, pmid = {30510226}, issn = {1476-4687}, } @article {pmid30510225, year = {2018}, author = {Tuchming, B}, title = {Long-sought decay of the Higgs boson seen.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {46-47}, doi = {10.1038/d41586-018-07405-x}, pmid = {30510225}, issn = {1476-4687}, } @article {pmid30510224, year = {2018}, author = {Baross, JA}, title = {The rocky road to biomolecules.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {42-43}, doi = {10.1038/d41586-018-07262-8}, pmid = {30510224}, issn = {1476-4687}, } @article {pmid30510179, year = {2019}, author = {Gold, DA and Katsuki, T and Li, Y and Yan, X and Regulski, M and Ibberson, D and Holstein, T and Steele, RE and Jacobs, DK and Greenspan, RJ}, title = {The genome of the jellyfish Aurelia and the evolution of animal complexity.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {96-104}, doi = {10.1038/s41559-018-0719-8}, pmid = {30510179}, issn = {2397-334X}, abstract = {We present the genome of the moon jellyfish Aurelia, a genome from a cnidarian with a medusa life stage. Our analyses suggest that gene gain and loss in Aurelia is comparable to what has been found in its morphologically simpler relatives-the anthozoan corals and sea anemones. RNA sequencing analysis does not support the hypothesis that taxonomically restricted (orphan) genes play an oversized role in the development of the medusa stage. Instead, genes broadly conserved across animals and eukaryotes play comparable roles throughout the life cycle. All life stages of Aurelia are significantly enriched in the expression of genes that are hypothesized to interact in protein networks found in bilaterian animals. Collectively, our results suggest that increased life cycle complexity in Aurelia does not correlate with an increased number of genes. This leads to two possible evolutionary scenarios: either medusozoans evolved their complex medusa life stage (with concomitant shifts into new ecological niches) primarily by re-working genetic pathways already present in the last common ancestor of cnidarians, or the earliest cnidarians had a medusa life stage, which was subsequently lost in the anthozoans. While we favour the earlier hypothesis, the latter is consistent with growing evidence that many of the earliest animals were more physically complex than previously hypothesized.}, } @article {pmid30510178, year = {2019}, author = {Jacobs, A and Carruthers, M and Eckmann, R and Yohannes, E and Adams, CE and Behrmann-Godel, J and Elmer, KR}, title = {Rapid niche expansion by selection on functional genomic variation after ecosystem recovery.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {77-86}, doi = {10.1038/s41559-018-0742-9}, pmid = {30510178}, issn = {2397-334X}, abstract = {It is well recognized that environmental degradation caused by human activities can result in dramatic losses of species and diversity. However, comparatively little is known about the ability of biodiversity to re-emerge following ecosystem recovery. Here, we show that a European whitefish subspecies, the gangfisch Coregonus lavaretus macrophthalmus, rapidly increased its ecologically functional diversity following the restoration of Lake Constance after anthropogenic eutrophication. In fewer than ten generations, gangfisch evolved a greater range of gill raker numbers (GRNs) to utilize a broader ecological niche. A sparse genetic architecture underlies this variation in GRN. Several co-expressed gene modules and genes showing signals of positive selection were associated with GRN and body shape. These were enriched for biological pathways related to trophic niche expansion in fishes. Our findings demonstrate the potential of functional diversity to expand following habitat restoration, given a fortuitous combination of genetic architecture, genetic diversity and selection.}, } @article {pmid30510177, year = {2019}, author = {Kayser, J and Schreck, CF and Gralka, M and Fusco, D and Hallatschek, O}, title = {Collective motion conceals fitness differences in crowded cellular populations.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {125-134}, doi = {10.1038/s41559-018-0734-9}, pmid = {30510177}, issn = {2397-334X}, support = {R01 GM115851/GM/NIGMS NIH HHS/United States ; }, abstract = {Many cellular populations are tightly packed, such as microbial colonies and biofilms, or tissues and tumours in multicellular organisms. The movement of one cell in these crowded assemblages requires motion of others, so that cell displacements are correlated over many cell diameters. Whenever movement is important for survival or growth, these correlated rearrangements could couple the evolutionary fate of different lineages. However, little is known about the interplay between mechanical forces and evolution in dense cellular populations. Here, by tracking slower-growing clones at the expanding edge of yeast colonies, we show that the collective motion of cells prevents costly mutations from being weeded out rapidly. Joint pushing by neighbouring cells generates correlated movements that suppress the differential displacements required for selection to act. This mechanical screening of fitness differences allows slower-growing mutants to leave more descendants than expected under non-mechanical models, thereby increasing their chance for evolutionary rescue. Our work suggests that, in crowded populations, cells cooperate with surrounding neighbours through inevitable mechanical interactions. This effect has to be considered when predicting evolutionary outcomes, such as the emergence of drug resistance or cancer evolution.}, } @article {pmid30510176, year = {2019}, author = {Han, AX and Maurer-Stroh, S and Russell, CA}, title = {Individual immune selection pressure has limited impact on seasonal influenza virus evolution.}, journal = {Nature ecology & evolution}, volume = {3}, number = {2}, pages = {302-311}, doi = {10.1038/s41559-018-0741-x}, pmid = {30510176}, issn = {2397-334X}, abstract = {Seasonal influenza viruses are subjected to strong selection as seen by the sequential replacement of existing viral populations on the emergence of new antigenic variants. However, the process of within-host de novo mutant generation and evolutionary selection that underlies these antigenic sweeps is poorly understood. Here, we investigate mutational patterns between evolutionarily closely related human seasonal influenza viruses using host age as a proxy for immune experience. The systematic analysis of >25,000 virus sequences showed that individuals with substantially differing immune histories were frequently (30-62%) infected by viruses with identical amino acid sequences. Viruses from immunologically inexperienced individuals were as likely to possess substitutions with potential phenotypic relevance as highly experienced individuals. Mutations likely to cause antigenic changes were rare among closely related viruses and not associated with extent of host immune experience. These findings suggest that individual immune positive selection plays a limited role in the evolution of seasonal influenza viruses.}, } @article {pmid30510174, year = {2019}, author = {Quesada, V and Freitas-Rodríguez, S and Miller, J and Pérez-Silva, JG and Jiang, ZF and Tapia, W and Santiago-Fernández, O and Campos-Iglesias, D and Kuderna, LFK and Quinzin, M and Álvarez, MG and Carrero, D and Beheregaray, LB and Gibbs, JP and Chiari, Y and Glaberman, S and Ciofi, C and Araujo-Voces, M and Mayoral, P and Arango, JR and Tamargo-Gómez, I and Roiz-Valle, D and Pascual-Torner, M and Evans, BR and Edwards, DL and Garrick, RC and Russello, MA and Poulakakis, N and Gaughran, SJ and Rueda, DO and Bretones, G and Marquès-Bonet, T and White, KP and Caccone, A and López-Otín, C}, title = {Giant tortoise genomes provide insights into longevity and age-related disease.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {87-95}, doi = {10.1038/s41559-018-0733-x}, pmid = {30510174}, issn = {2397-334X}, support = {U01 MH106874/MH/NIMH NIH HHS/United States ; }, abstract = {Giant tortoises are among the longest-lived vertebrate animals and, as such, provide an excellent model to study traits like longevity and age-related diseases. However, genomic and molecular evolutionary information on giant tortoises is scarce. Here, we describe a global analysis of the genomes of Lonesome George-the iconic last member of Chelonoidis abingdonii-and the Aldabra giant tortoise (Aldabrachelys gigantea). Comparison of these genomes with those of related species, using both unsupervised and supervised analyses, led us to detect lineage-specific variants affecting DNA repair genes, inflammatory mediators and genes related to cancer development. Our study also hints at specific evolutionary strategies linked to increased lifespan, and expands our understanding of the genomic determinants of ageing. These new genome sequences also provide important resources to help the efforts for restoration of giant tortoise populations.}, } @article {pmid30510173, year = {2019}, author = {Song, D and Meng, J and Cheng, J and Fan, Z and Chen, P and Ruan, H and Tu, Z and Kang, N and Li, N and Xu, Y and Wang, X and Shu, F and Mu, L and Li, T and Ren, W and Lin, X and Zhu, J and Fang, X and Amrein, MW and Wu, W and Yan, LT and Lü, J and Xia, T and Shi, Y}, title = {Pseudomonas aeruginosa quorum-sensing metabolite induces host immune cell death through cell surface lipid domain dissolution.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {97-111}, doi = {10.1038/s41564-018-0290-8}, pmid = {30510173}, issn = {2058-5276}, support = {R01 AI120489/AI/NIAID NIH HHS/United States ; }, abstract = {Bacterial quorum-sensing autoinducers are small chemicals released to control microbial community behaviours. N-(3-oxo-dodecanoyl) homoserine lactone, the autoinducer of the Pseudomonas aeruginosa LasI-LasR circuitry, triggers significant cell death in lymphocytes. We found that this molecule is incorporated into the mammalian plasma membrane and induces dissolution of eukaryotic lipid domains. This event expels tumour necrosis factor receptor 1 into the disordered lipid phase for its spontaneous trimerization without its ligand and drives caspase 3-caspase 8-mediated apoptosis. In vivo, P. aeruginosa releases N-(3-oxo-dodecanoyl) homoserine lactone to suppress host immunity for its own better survival; conversely, blockage of caspases strongly reduces the severity of the infection. This work reveals an unknown communication method between microorganisms and the mammalian host and suggests interventions of bacterial infections by intercepting quorum-sensing signalling.}, } @article {pmid30510172, year = {2019}, author = {Schubert, B and Maddamsetti, R and Nyman, J and Farhat, MR and Marks, DS}, title = {Genome-wide discovery of epistatic loci affecting antibiotic resistance in Neisseria gonorrhoeae using evolutionary couplings.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {328-338}, doi = {10.1038/s41564-018-0309-1}, pmid = {30510172}, issn = {2058-5276}, abstract = {Genome analysis should allow the discovery of interdependent loci that together cause antibiotic resistance. In practice, however, the vast number of possible epistatic interactions erodes statistical power. Here, we extend an approach that has been successfully used to identify epistatic residues in proteins to infer genomic loci that are strongly coupled. This approach reduces the number of tests required for an epistatic genome-wide association study of antibiotic resistance and increases the likelihood of identifying causal epistasis. We discovered 38 loci and 240 epistatic pairs that influence the minimum inhibitory concentrations of 5 different antibiotics in 1,102 isolates of Neisseria gonorrhoeae that were confirmed in a second dataset of 495 isolates. Many known resistance-affecting loci were recovered; however, the majority of associations occurred in unreported genes, such as murE. About half of the discovered epistasis involved at least one locus previously associated with antibiotic resistance, including interactions between gyrA and parC. Still, many combinations involved unreported loci and genes. While most variation in minimum inhibitory concentrations could be explained by identified loci, epistasis substantially increased explained phenotypic variance. Our work provides a systematic identification of epistasis affecting antibiotic resistance in N. gonorrhoeae and a generalizable approach for epistatic genome-wide association studies.}, } @article {pmid30510171, year = {2019}, author = {Daly, RA and Roux, S and Borton, MA and Morgan, DM and Johnston, MD and Booker, AE and Hoyt, DW and Meulia, T and Wolfe, RA and Hanson, AJ and Mouser, PJ and Moore, JD and Wunch, K and Sullivan, MB and Wrighton, KC and Wilkins, MJ}, title = {Viruses control dominant bacteria colonizing the terrestrial deep biosphere after hydraulic fracturing.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {352-361}, doi = {10.1038/s41564-018-0312-6}, pmid = {30510171}, issn = {2058-5276}, abstract = {The deep terrestrial biosphere harbours a substantial fraction of Earth's biomass and remains understudied compared with other ecosystems. Deep biosphere life primarily consists of bacteria and archaea, yet knowledge of their co-occurring viruses is poor. Here, we temporally catalogued viral diversity from five deep terrestrial subsurface locations (hydraulically fractured wells), examined virus-host interaction dynamics and experimentally assessed metabolites from cell lysis to better understand viral roles in this ecosystem. We uncovered high viral diversity, rivalling that of peatland soil ecosystems, despite low host diversity. Many viral operational taxonomic units were predicted to infect Halanaerobium, the dominant microorganism in these ecosystems. Examination of clustered regularly interspaced short palindromic repeats-CRISPR-associated proteins (CRISPR-Cas) spacers elucidated lineage-specific virus-host dynamics suggesting active in situ viral predation of Halanaerobium. These dynamics indicate repeated viral encounters and changing viral host range across temporally and geographically distinct shale formations. Laboratory experiments showed that prophage-induced Halanaerobium lysis releases intracellular metabolites that can sustain key fermentative metabolisms, supporting the persistence of microorganisms in this ecosystem. Together, these findings suggest that diverse and active viral populations play critical roles in driving strain-level microbial community development and resource turnover within this deep terrestrial subsurface ecosystem.}, } @article {pmid30510170, year = {2019}, author = {Huang, J and Kelly, CP and Bakirtzi, K and Villafuerte Gálvez, JA and Lyras, D and Mileto, SJ and Larcombe, S and Xu, H and Yang, X and Shields, KS and Zhu, W and Zhang, Y and Goldsmith, JD and Patel, IJ and Hansen, J and Huang, M and Yla-Herttuala, S and Moss, AC and Paredes-Sabja, D and Pothoulakis, C and Shah, YM and Wang, J and Chen, X}, title = {Clostridium difficile toxins induce VEGF-A and vascular permeability to promote disease pathogenesis.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {269-279}, doi = {10.1038/s41564-018-0300-x}, pmid = {30510170}, issn = {2058-5276}, abstract = {Clostridium difficile infection (CDI) is mediated by two major exotoxins, toxin A (TcdA) and toxin B (TcdB), that damage the colonic epithelial barrier and induce inflammatory responses. The function of the colonic vascular barrier during CDI has been relatively understudied. Here we report increased colonic vascular permeability in CDI mice and elevated vascular endothelial growth factor A (VEGF-A), which was induced in vivo by infection with TcdA- and/or TcdB-producing C. difficile strains but not with a TcdA-TcdB- isogenic mutant. TcdA or TcdB also induced the expression of VEGF-A in human colonic mucosal biopsies. Hypoxia-inducible factor signalling appeared to mediate toxin-induced VEGF production in colonocytes, which can further stimulate human intestinal microvascular endothelial cells. Both neutralization of VEGF-A and inhibition of its signalling pathway attenuated CDI in vivo. Compared to healthy controls, CDI patients had significantly higher serum VEGF-A that subsequently decreased after treatment. Our findings indicate critical roles for toxin-induced VEGF-A and colonic vascular permeability in CDI pathogenesis and may also point to the pathophysiological significance of the gut vascular barrier in response to virulence factors of enteric pathogens. As an alternative to pathogen-targeted therapy, this study may enable new host-directed therapeutic approaches for severe, refractory CDI.}, } @article {pmid30510169, year = {2019}, author = {Tanaka, S and Schweizer, G and Rössel, N and Fukada, F and Thines, M and Kahmann, R}, title = {Neofunctionalization of the secreted Tin2 effector in the fungal pathogen Ustilago maydis.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {251-257}, doi = {10.1038/s41564-018-0304-6}, pmid = {30510169}, issn = {2058-5276}, abstract = {Plant-pathogenic fungi hijack their hosts by secreting effector proteins. Effectors serve to suppress plant immune responses and modulate the host metabolism to benefit the pathogen. Smut fungi are biotrophic pathogens that also parasitize important cereals, including maize1. Symptom development is usually restricted to the plant inflorescences. Ustilago maydis is an exception in its ability to cause tumours in both inflorescences and leaves of maize, and in inducing anthocyanin biosynthesis through the secreted Tin2 effector2,3. How the unique lifestyle of U. maydis has evolved remains to be elucidated. Here we show that Tin2 in U. maydis has been neofunctionalized. We functionally compared Tin2 effectors of U. maydis and the related smut Sporisorium reilianum, which results in symptoms only in the inflorescences of maize and fails to induce anthocyanin. We show that Tin2 effectors from both fungi target distinct paralogues of a maize protein kinase, leading to stabilization and inhibition, respectively. An ancestral Tin2 effector functionally replaced the virulence function of S. reilianum Tin2 but failed to induce anthocyanin, and was unable to substitute for Tin2 in U. maydis. This shows that Tin2 in U. maydis has acquired a specialized function, probably connected to the distinct pathogenic lifestyle of this fungus.}, } @article {pmid30510168, year = {2019}, author = {Eddowes, LA and Al-Hourani, K and Ramamurthy, N and Frankish, J and Baddock, HT and Sandor, C and Ryan, JD and Fusco, DN and Arezes, J and Giannoulatou, E and Boninsegna, S and Chevaliez, S and Owens, BMJ and Sun, CC and Fabris, P and Giordani, MT and Martines, D and Vukicevic, S and Crowe, J and Lin, HY and Rehwinkel, J and McHugh, PJ and Binder, M and Babitt, JL and Chung, RT and Lawless, MW and Armitage, AE and Webber, C and Klenerman, P and Drakesmith, H}, title = {Antiviral activity of bone morphogenetic proteins and activins.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {339-351}, doi = {10.1038/s41564-018-0301-9}, pmid = {30510168}, issn = {2058-5276}, abstract = {Understanding the control of viral infections is of broad importance. Chronic hepatitis C virus (HCV) infection causes decreased expression of the iron hormone hepcidin, which is regulated by hepatic bone morphogenetic protein (BMP)/SMAD signalling. We found that HCV infection and the BMP/SMAD pathway are mutually antagonistic. HCV blunted induction of hepcidin expression by BMP6, probably via tumour necrosis factor (TNF)-mediated downregulation of the BMP co-receptor haemojuvelin. In HCV-infected patients, disruption of the BMP6/hepcidin axis and genetic variation associated with the BMP/SMAD pathway predicted the outcome of infection, suggesting that BMP/SMAD activity influences antiviral immunity. Correspondingly, BMP6 regulated a gene repertoire reminiscent of type I interferon (IFN) signalling, including upregulating interferon regulatory factors (IRFs) and downregulating an inhibitor of IFN signalling, USP18. Moreover, in BMP-stimulated cells, SMAD1 occupied loci across the genome, similar to those bound by IRF1 in IFN-stimulated cells. Functionally, BMP6 enhanced the transcriptional and antiviral response to IFN, but BMP6 and related activin proteins also potently blocked HCV replication independently of IFN. Furthermore, BMP6 and activin A suppressed growth of HBV in cell culture, and activin A inhibited Zika virus replication alone and in combination with IFN. The data establish an unappreciated important role for BMPs and activins in cellular antiviral immunity, which acts independently of, and modulates, IFN.}, } @article {pmid30510167, year = {2019}, author = {Briard, B and Karki, R and Malireddi, RKS and Bhattacharya, A and Place, DE and Mavuluri, J and Peters, JL and Vogel, P and Yamamoto, M and Kanneganti, TD}, title = {Fungal ligands released by innate immune effectors promote inflammasome activation during Aspergillus fumigatus infection.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {316-327}, doi = {10.1038/s41564-018-0298-0}, pmid = {30510167}, issn = {2058-5276}, abstract = {Invasive pulmonary aspergillosis causes substantial mortality in immunocompromised individuals. Recognition of Aspergillus fumigatus by the host immune system leads to activation of the inflammasome, which provides protection against infection. However, regulation of inflammasome activation at the molecular level is poorly understood. Here, we describe two distinct pathways that coordinately control inflammasome activation during A. fumigatus infection. The C-type lectin receptor pathway activates both MAPK and NF-κB signalling, which leads to induction of downstream mediators, such as the transcription factor IRF1, and also primes the inflammasomes. Toll-like receptor signalling through the adaptor molecules MyD88 and TRIF in turn mediates efficient activation of IRF1, which induces IRGB10 expression. IRGB10 targets the fungal cell wall, and the antifungal activity of IRGB10 causes hyphae damage, modifies the A. fumigatus surface and inhibits fungal growth. We also demonstrate that one of the major fungal pathogen-associated molecular patterns, β-glucan, directly triggers inflammasome assembly. Thus, the concerted activation of both Toll-like receptors and C-type lectin receptors is required for IRF1-mediated IRGB10 regulation, which is a key event governing ligand release and inflammasome activation upon A. fumigatus infection.}, } @article {pmid30510161, year = {2018}, author = {Jackson, MD and Blundy, J and Sparks, RSJ}, title = {Chemical differentiation, cold storage and remobilization of magma in the Earth's crust.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {405-409}, doi = {10.1038/s41586-018-0746-2}, pmid = {30510161}, issn = {1476-4687}, abstract = {The formation, storage and chemical differentiation of magma in the Earth's crust is of fundamental importance in igneous geology and volcanology. Recent data are challenging the high-melt-fraction 'magma chamber' paradigm that has underpinned models of crustal magmatism for over a century, suggesting instead that magma is normally stored in low-melt-fraction 'mush reservoirs'1-9. A mush reservoir comprises a porous and permeable framework of closely packed crystals with melt present in the pore space1,10. However, many common features of crustal magmatism have not yet been explained by either the 'chamber' or 'mush reservoir' concepts1,11. Here we show that reactive melt flow is a critical, but hitherto neglected, process in crustal mush reservoirs, caused by buoyant melt percolating upwards through, and reacting with, the crystals10. Reactive melt flow in mush reservoirs produces the low-crystallinity, chemically differentiated (silicic) magmas that ascend to form shallower intrusions or erupt to the surface11-13. These magmas can host much older crystals, stored at low and even sub-solidus temperatures, consistent with crystal chemistry data6-9. Changes in local bulk composition caused by reactive melt flow, rather than large increases in temperature, produce the rapid increase in melt fraction that remobilizes these cool- or cold-stored crystals. Reactive flow can also produce bimodality in magma compositions sourced from mid- to lower-crustal reservoirs14,15. Trace-element profiles generated by reactive flow are similar to those observed in a well studied reservoir now exposed at the surface16. We propose that magma storage and differentiation primarily occurs by reactive melt flow in long-lived mush reservoirs, rather than by the commonly invoked process of fractional crystallization in magma chambers14.}, } @article {pmid30510160, year = {2019}, author = {Manipatruni, S and Nikonov, DE and Lin, CC and Gosavi, TA and Liu, H and Prasad, B and Huang, YL and Bonturim, E and Ramesh, R and Young, IA}, title = {Scalable energy-efficient magnetoelectric spin-orbit logic.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {35-42}, doi = {10.1038/s41586-018-0770-2}, pmid = {30510160}, issn = {1476-4687}, abstract = {Since the early 1980s, most electronics have relied on the use of complementary metal-oxide-semiconductor (CMOS) transistors. However, the principles of CMOS operation, involving a switchable semiconductor conductance controlled by an insulating gate, have remained largely unchanged, even as transistors are miniaturized to sizes of 10 nanometres. We investigated what dimensionally scalable logic technology beyond CMOS could provide improvements in efficiency and performance for von Neumann architectures and enable growth in emerging computing such as artifical intelligence. Such a computing technology needs to allow progressive miniaturization, reduce switching energy, improve device interconnection and provide a complete logic and memory family. Here we propose a scalable spintronic logic device that operates via spin-orbit transduction (the coupling of an electron's angular momentum with its linear momentum) combined with magnetoelectric switching. The device uses advanced quantum materials, especially correlated oxides and topological states of matter, for collective switching and detection. We describe progress in magnetoelectric switching and spin-orbit detection of state, and show that in comparison with CMOS technology our device has superior switching energy (by a factor of 10 to 30), lower switching voltage (by a factor of 5) and enhanced logic density (by a factor of 5). In addition, its non-volatility enables ultralow standby power, which is critical to modern computing. The properties of our device indicate that the proposed technology could enable the development of multi-generational computing.}, } @article {pmid30510064, year = {2018}, author = {Preissler, S and Ron, D}, title = {Erratum: Early Events in the Endoplasmic Reticulum Unfolded Protein Response.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, doi = {10.1101/cshperspect.a037309}, pmid = {30510064}, issn = {1943-0264}, } @article {pmid30510063, year = {2018}, author = {Lu, Z and Chang, HY}, title = {The RNA Base-Pairing Problem and Base-Pairing Solutions.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, pmid = {30510063}, issn = {1943-0264}, support = {K99 HG009662/HG/NHGRI NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 HG004361/HG/NHGRI NIH HHS/United States ; }, abstract = {SUMMARYRNA molecules are folded into structures and complexes to perform a wide variety of functions. Determination of RNA structures and their interactions is a fundamental problem in RNA biology. Most RNA molecules in living cells are large and dynamic, posing unique challenges to structure analysis. Here we review progress in RNA structure analysis, focusing on methods that use the "cross-link, proximally ligate, and sequence" principle for high-throughput detection of base-pairing interactions in living cells. Beginning with a comparison of commonly used methods in structure determination and a brief historical account of psoralen cross-linking studies, we highlight the important features of cross-linking methods and new biological insights into RNA structures and interactions from recent studies. Further improvement of these cross-linking methods and application to previously intractable problems will shed new light on the mechanisms of the "modern RNA world."}, } @article {pmid30510062, year = {2018}, author = {Frank, M}, title = {Working for a Scientific Society.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, doi = {10.1101/cshperspect.a032888}, pmid = {30510062}, issn = {1943-0264}, abstract = {Opportunities for employment of PhD scientists exist within the world of scientific societies. Societies exist to serve the needs of their scientific or engineering constituencies. As membership organizations, they provide their constituents with access to meetings, publications (both books and journals), educational programs, and advocacy assistance. Within many of these societies, leadership positions and associated coordinator/analyst positions can be filled by someone with a PhD. Examples of positions in societies include science policy/government relations, education, publications, communications, and executive departments. Interested PhDs should demonstrate their interest by volunteering to participate in society outreach or committee activities. The critical element is to remember that as a PhD you have the critical thinking and problem-solving ability to succeed in whatever career you pursue. The key is to demonstrate that these abilities are applicable to the available positions in the association.}, } @article {pmid30510061, year = {2018}, author = {Chao, JA and Lionnet, T}, title = {Imaging the Life and Death of mRNAs in Single Cells.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, doi = {10.1101/cshperspect.a032086}, pmid = {30510061}, issn = {1943-0264}, abstract = {SUMMARYRNA plays a central role in gene expression from its transcription in the nucleus through translation and degradation in the cytoplasm. Technological advances in fluorescent microscopy and labeling methodologies have made it possible to detect single molecules of RNA in both fixed and living cells. Here, we focus on the recent developments in RNA imaging that have allowed quantitatively measuring the lives of individual transcripts from birth to death and all the events in between in single cells and tissues. Direct observation of RNAs within their native cellular environment has revealed a complex layer of spatial and temporal regulation that has profoundly impacted our understanding of RNA biology.}, } @article {pmid30510007, year = {2019}, author = {Sun, X and Stefanetti, G and Berti, F and Kasper, DL}, title = {Polysaccharide structure dictates mechanism of adaptive immune response to glycoconjugate vaccines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {1}, pages = {193-198}, doi = {10.1073/pnas.1816401115}, pmid = {30510007}, issn = {1091-6490}, support = {R01 AI089915/AI/NIAID NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, abstract = {Glycoconjugate vaccines are among the most effective interventions for preventing several serious infectious diseases. Covalent linkage of the bacterial capsular polysaccharide to a carrier protein provides CD4+ T cells with epitopes that facilitate a memory response to the polysaccharide. Classically, the mechanism responsible for antigen processing was thought to be similar to what was known for hapten-carrier conjugates: protease digestion of the carrier protein in the endosome and presentation of a resulting peptide to the T cell receptor on classical peptide-recognizing CD4+ T cells. Recently, an alternative mechanism has been shown to be responsible for the memory response to some glycoconjugates. Processing of both the protein and the polysaccharide creates glycopeptides in the endosome of antigen-presenting cells. For presentation, the peptide portion of the glycopeptide is bound to MHCII, allowing the covalently linked glycan to activate carbohydrate-specific helper CD4+ T cells (Tcarbs). Herein, we assessed whether this same mechanism applies to conjugates prepared from other capsular polysaccharides. All of the glycoconjugates tested induced Tcarb-dependent responses except that made with group C Neisseria meningitidis; in the latter case, only peptides generated from the carrier protein were critical for helper T cell recognition. Digestion of this acid-sensitive polysaccharide, a linear homopolymer of α(2 → 9)-linked sialic acid, to the size of the monomeric unit resulted in a dominant CD4+ T cell response to peptides in the context of MHCII. Our results show that different mechanisms of presentation, based on the structure of the carbohydrate, are operative in response to different glycoconjugate vaccines.}, } @article {pmid30510006, year = {2018}, author = {Garieri, M and Stamoulis, G and Blanc, X and Falconnet, E and Ribaux, P and Borel, C and Santoni, F and Antonarakis, SE}, title = {Extensive cellular heterogeneity of X inactivation revealed by single-cell allele-specific expression in human fibroblasts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13015-13020}, doi = {10.1073/pnas.1806811115}, pmid = {30510006}, issn = {1091-6490}, abstract = {X-chromosome inactivation (XCI) provides a dosage compensation mechanism where, in each female cell, one of the two X chromosomes is randomly silenced. However, some genes on the inactive X chromosome and outside the pseudoautosomal regions escape from XCI and are expressed from both alleles (escapees). We investigated XCI at single-cell resolution combining deep single-cell RNA sequencing with whole-genome sequencing to examine allelic-specific expression in 935 primary fibroblast and 48 lymphoblastoid single cells from five female individuals. In this framework we integrated an original method to identify and exclude doublets of cells. In fibroblast cells, we have identified 55 genes as escapees including five undescribed escapee genes. Moreover, we observed that all genes exhibit a variable propensity to escape XCI in each cell and cell type and that each cell displays a distinct expression profile of the escapee genes. A metric, the Inactivation Score-defined as the mean of the allelic expression profiles of the escapees per cell-enables us to discover a heterogeneous and continuous degree of cellular XCI with extremes represented by "inactive" cells, i.e., cells exclusively expressing the escaping genes from the active X chromosome and "escaping" cells expressing the escapees from both alleles. We found that this effect is associated with cell-cycle phases and, independently, with the XIST expression level, which is higher in the quiescent phase (G0). Single-cell allele-specific expression is a powerful tool to identify novel escapees in different tissues and provide evidence of an unexpected cellular heterogeneity of XCI.}, } @article {pmid30510005, year = {2018}, author = {Buey, RM and Fernández-Justel, D and de Pereda, JM and Revuelta, JL and Schürmann, P and Buchanan, BB and Balsera, M}, title = {Ferredoxin-linked flavoenzyme defines a family of pyridine nucleotide-independent thioredoxin reductases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12967-12972}, doi = {10.1073/pnas.1812781115}, pmid = {30510005}, issn = {1091-6490}, abstract = {Ferredoxin-dependent thioredoxin reductase was identified 35 y ago in the fermentative bacterium Clostridium pasteurianum [Hammel KE, Cornwell KL, Buchanan BB (1983) Proc Natl Acad Sci USA 80:3681-3685]. The enzyme, a flavoprotein, was strictly dependent on ferredoxin as reductant and was inactive with either NADPH or NADH. This early work has not been further pursued. We have recently reinvestigated the problem and confirmed that the enzyme, here designated ferredoxin-dependent flavin thioredoxin reductase (FFTR), is a flavoprotein. The enzyme differs from ferredoxin-thioredoxin reductase (FTR), which has a signature [4Fe-4S] cluster, but shows structural similarities to NADP-dependent thioredoxin reductase (NTR). Comparative amino acid sequence analysis showed that FFTR is present in a number of clostridial species, some of which lack both FTR and an archetypal NTR. We have isolated, crystallized, and determined the structural properties of FFTR from a member of this group, Clostridium acetobutylicum, both alone and in complex with Trx. The structures showed an elongated FFTR homodimer, each monomer comprising two Rossmann domains and a noncovalently bound FAD cofactor that exposes the isoalloxazine ring to the solvent. The FFTR structures revealed an alternative domain organization compared with NTR that enables the enzyme to accommodate Fdx rather than NADPH. The results suggest that FFTR exists in a range of conformations with varying degrees of domain separation in solution and that the stacking between the two redox-active groups for the transfer of reducing equivalents results in a profound structural reorganization. A mechanism in accord with the findings is proposed.}, } @article {pmid30510004, year = {2018}, author = {Gould, AL and Zhang, V and Lamberti, L and Jones, EW and Obadia, B and Korasidis, N and Gavryushkin, A and Carlson, JM and Beerenwinkel, N and Ludington, WB}, title = {Microbiome interactions shape host fitness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11951-E11960}, doi = {10.1073/pnas.1809349115}, pmid = {30510004}, issn = {1091-6490}, support = {DP5 OD017851/OD/NIH HHS/United States ; }, abstract = {Gut bacteria can affect key aspects of host fitness, such as development, fecundity, and lifespan, while the host, in turn, shapes the gut microbiome. However, it is unclear to what extent individual species versus community interactions within the microbiome are linked to host fitness. Here, we combinatorially dissect the natural microbiome of Drosophila melanogaster and reveal that interactions between bacteria shape host fitness through life history tradeoffs. Empirically, we made germ-free flies colonized with each possible combination of the five core species of fly gut bacteria. We measured the resulting bacterial community abundances and fly fitness traits, including development, reproduction, and lifespan. The fly gut promoted bacterial diversity, which, in turn, accelerated development, reproduction, and aging: Flies that reproduced more died sooner. From these measurements, we calculated the impact of bacterial interactions on fly fitness by adapting the mathematics of genetic epistasis to the microbiome. Development and fecundity converged with higher diversity, suggesting minimal dependence on interactions. However, host lifespan and microbiome abundances were highly dependent on interactions between bacterial species. Higher-order interactions (involving three, four, and five species) occurred in 13-44% of possible cases depending on the trait, with the same interactions affecting multiple traits, a reflection of the life history tradeoff. Overall, we found these interactions were frequently context-dependent and often had the same magnitude as individual species themselves, indicating that the interactions can be as important as the individual species in gut microbiomes.}, } @article {pmid30510003, year = {2018}, author = {Shibata, S and Miyake, K and Tateishi, T and Yoshikawa, S and Yamanishi, Y and Miyazaki, Y and Inase, N and Karasuyama, H}, title = {Basophils trigger emphysema development in a murine model of COPD through IL-4-mediated generation of MMP-12-producing macrophages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13057-13062}, doi = {10.1073/pnas.1813927115}, pmid = {30510003}, issn = {1091-6490}, abstract = {Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. It has generally been considered a non-Th2-type lung disorder, characterized by progressive airflow limitation with inflammation and emphysema, but its cellular and molecular mechanism remains ill defined, compared with that of asthma characterized by reversible airway obstruction. Here we show a previously unappreciated role for basophils at the initiation phase of emphysema formation in an elastase-induced murine model of COPD in that basophils represent less than 1% of lung-infiltrating cells. Intranasal elastase instillation elicited the recruitment of monocytes to the lung, followed by differentiation into interstitial macrophages (IMs) but rarely alveolar macrophages (AMs). Matrix metalloproteinase-12 (MMP-12) contributing to emphysema formation was highly expressed by IMs rather than AMs, in contrast to the prevailing assumption. Experiments using a series of genetically engineered mice suggested that basophil-derived IL-4, a Th2 cytokine, acted on lung-infiltrating monocytes to promote their differentiation into MMP-12-producing IMs that resulted in the destruction of alveolar walls and led to emphysema development. Indeed, mice deficient for IL-4 only in basophils failed to generate pathogenic MMP-12-producing IMs and hence develop emphysema. Thus, the basophil-derived IL-4/monocyte-derived IM/MMP-12 axis plays a crucial role in emphysema formation and therefore may be a potential target to slow down emphysema progression at the initiation phase of COPD.}, } @article {pmid30510002, year = {2018}, author = {Yu, TY and Kimble, MT and Symington, LS}, title = {Sae2 antagonizes Rad9 accumulation at DNA double-strand breaks to attenuate checkpoint signaling and facilitate end resection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11961-E11969}, doi = {10.1073/pnas.1816539115}, pmid = {30510002}, issn = {1091-6490}, support = {P01 CA174653/CA/NCI NIH HHS/United States ; R35 GM126997/GM/NIGMS NIH HHS/United States ; }, abstract = {The Mre11-Rad50-Xrs2NBS1 complex plays important roles in the DNA damage response by activating the Tel1ATM kinase and catalyzing 5'-3' resection at DNA double-strand breaks (DSBs). To initiate resection, Mre11 endonuclease nicks the 5' strands at DSB ends in a reaction stimulated by Sae2CtIP Accordingly, Mre11-nuclease deficient (mre11-nd) and sae2Δ mutants are expected to exhibit similar phenotypes; however, we found several notable differences. First, sae2Δ cells exhibit greater sensitivity to genotoxins than mre11-nd cells. Second, sae2Δ is synthetic lethal with sgs1Δ, whereas the mre11-nd sgs1Δ mutant is viable. Third, Sae2 attenuates the Tel1-Rad53CHK2 checkpoint and antagonizes Rad953BP1 accumulation at DSBs independent of Mre11 nuclease. We show that Sae2 competes with other Tel1 substrates, thus reducing Rad9 binding to chromatin and to Rad53. We suggest that persistent Sae2 binding at DSBs in the mre11-nd mutant counteracts the inhibitory effects of Rad9 and Rad53 on Exo1 and Dna2-Sgs1-mediated resection, accounting for the different phenotypes conferred by mre11-nd and sae2Δ mutations. Collectively, these data show a resection initiation independent role for Sae2 at DSBs by modulating the DNA damage checkpoint.}, } @article {pmid30510001, year = {2018}, author = {Manna, A and Zhao, H and Wada, J and Balagopalan, L and Tagad, HD and Appella, E and Schuck, P and Samelson, LE}, title = {Cooperative assembly of a four-molecule signaling complex formed upon T cell antigen receptor activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11914-E11923}, doi = {10.1073/pnas.1817142115}, pmid = {30510001}, issn = {1091-6490}, abstract = {The T cell antigen receptor encounters foreign antigen during the immune response. Receptor engagement leads to activation of specific protein tyrosine kinases, which then phosphorylate multiple enzymes and adapter proteins. One such enzyme, phospholipase-Cγ1, is responsible for cleavage of a plasma membrane lipid substrate, a phosphoinositide, into two second messengers, diacylglycerol, which activates several enzymes including protein kinase C, and an inositol phosphate, which induces intracellular calcium elevation. In T cells, phospholipase-Cγ1 is recruited to the plasma membrane as part of a four-protein complex containing three adapter molecules. We have used recombinant proteins and synthetic phosphopeptides to reconstitute this quaternary complex in vitro. Extending biophysical tools to study concurrent interactions of the four protein components, we demonstrated the formation and determined the composition of the quaternary complex using multisignal analytical ultracentrifugation, and we characterized the thermodynamic driving forces of assembly by isothermal calorimetry. We demonstrate that the four proteins reversibly associate in a circular arrangement of binding interfaces, each protein interacting with two others. Three interactions are of high affinity, and the fourth is of low affinity, with the assembly of the quaternary complex exhibiting significant enthalpy-entropy compensation as in an entropic switch. Formation of this protein complex enables subsequent recruitment of additional molecules needed to activate phospholipase-Cγ1. Understanding the formation of this complex is fundamental to full characterization of a central pathway in T cell activation. Such knowledge is critical to developing ways in which this pathway can be selectively inhibited.}, } @article {pmid30510000, year = {2018}, author = {Zaldivar, D and Rauch, A and Logothetis, NK and Goense, J}, title = {Two distinct profiles of fMRI and neurophysiological activity elicited by acetylcholine in visual cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12073-E12082}, doi = {10.1073/pnas.1808507115}, pmid = {30510000}, issn = {1091-6490}, abstract = {Cholinergic neuromodulation is involved in all aspects of sensory processing and is crucial for processes such as attention, learning and memory, etc. However, despite the known roles of acetylcholine (ACh), we still do not how to disentangle ACh contributions from sensory or task-evoked changes in functional magnetic resonance imaging (fMRI). Here, we investigated the effects of local injection of ACh on fMRI and neural signals in the primary visual cortex (V1) of anesthetized macaques by combining pharmaco-based MRI (phMRI) with electrophysiological recordings, using single electrodes and electrode arrays. We found that local injection of ACh elicited two distinct profiles of fMRI and neurophysiological activity, depending on the distance from the injector. Near the injection site, we observed an increase in the baseline blood oxygen-level-dependent (BOLD) and cerebral blood flow (CBF) responses, while their visual modulation decreased. In contrast, further from the injection site, we observed an increase in the visually induced BOLD and CBF modulation without changes in baseline. Neurophysiological recordings suggest that the spatial correspondence between fMRI responses and neural activity does not change in the gamma, high-gamma, and multiunit activity (MUA) bands. The results near the injection site suggest increased inhibitory drive and decreased metabolism, contrasting to the far region. These changes are thought to reflect the kinetics of ACh and its metabolism to choline.}, } @article {pmid30509999, year = {2019}, author = {Takahashi, A and Nagata, M and Gupta, A and Matsushita, Y and Yamaguchi, T and Mizuhashi, K and Maki, K and Ruellas, AC and Cevidanes, LS and Kronenberg, HM and Ono, N and Ono, W}, title = {Autocrine regulation of mesenchymal progenitor cell fates orchestrates tooth eruption.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {2}, pages = {575-580}, doi = {10.1073/pnas.1810200115}, pmid = {30509999}, issn = {1091-6490}, support = {R01 DE026666/DE/NIDCR NIH HHS/United States ; R03 DE027421/DE/NIDCR NIH HHS/United States ; }, abstract = {Formation of functional skeletal tissues requires highly organized steps of mesenchymal progenitor cell differentiation. The dental follicle (DF) surrounding the developing tooth harbors mesenchymal progenitor cells for various differentiated cells constituting the tooth root-bone interface and coordinates tooth eruption in a manner dependent on signaling by parathyroid hormone-related peptide (PTHrP) and the PTH/PTHrP receptor (PPR). However, the identity of mesenchymal progenitor cells in the DF and how they are regulated by PTHrP-PPR signaling remain unknown. Here, we show that the PTHrP-PPR autocrine signal maintains physiological cell fates of DF mesenchymal progenitor cells to establish the functional periodontal attachment apparatus and orchestrates tooth eruption. A single-cell RNA-seq analysis revealed cellular heterogeneity of PTHrP+ cells, wherein PTHrP+ DF subpopulations abundantly express PPR. Cell lineage analysis using tamoxifen-inducible PTHrP-creER mice revealed that PTHrP+ DF cells differentiate into cementoblasts on the acellular cementum, periodontal ligament cells, and alveolar cryptal bone osteoblasts during tooth root formation. PPR deficiency induced a cell fate shift of PTHrP+ DF mesenchymal progenitor cells to nonphysiological cementoblast-like cells precociously forming the cellular cementum on the root surface associated with up-regulation of Mef2c and matrix proteins, resulting in loss of the proper periodontal attachment apparatus and primary failure of tooth eruption, closely resembling human genetic conditions caused by PPR mutations. These findings reveal a unique mechanism whereby proper cell fates of mesenchymal progenitor cells are tightly maintained by an autocrine system mediated by PTHrP-PPR signaling to achieve functional formation of skeletal tissues.}, } @article {pmid30509998, year = {2018}, author = {Pelletier, TA and Carstens, BC and Tank, DC and Sullivan, J and Espíndola, A}, title = {Predicting plant conservation priorities on a global scale.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13027-13032}, doi = {10.1073/pnas.1804098115}, pmid = {30509998}, issn = {1091-6490}, abstract = {The conservation status of most plant species is currently unknown, despite the fundamental role of plants in ecosystem health. To facilitate the costly process of conservation assessment, we developed a predictive protocol using a machine-learning approach to predict conservation status of over 150,000 land plant species. Our study uses open-source geographic, environmental, and morphological trait data, making this the largest assessment of conservation risk to date and the only global assessment for plants. Our results indicate that a large number of unassessed species are likely at risk and identify several geographic regions with the highest need of conservation efforts, many of which are not currently recognized as regions of global concern. By providing conservation-relevant predictions at multiple spatial and taxonomic scales, predictive frameworks such as the one developed here fill a pressing need for biodiversity science.}, } @article {pmid30509997, year = {2018}, author = {Andersson, KME and Wasén, C and Juzokaite, L and Leifsdottir, L and Erlandsson, MC and Silfverswärd, ST and Stokowska, A and Pekna, M and Pekny, M and Olmarker, K and Heckemann, RA and Kalm, M and Bokarewa, MI}, title = {Inflammation in the hippocampus affects IGF1 receptor signaling and contributes to neurological sequelae in rheumatoid arthritis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12063-E12072}, doi = {10.1073/pnas.1810553115}, pmid = {30509997}, issn = {1091-6490}, support = {MR/L01632X/1//Medical Research Council/United Kingdom ; }, abstract = {Rheumatoid arthritis (RA) is an inflammatory joint disease with a neurological component including depression, cognitive deficits, and pain, which substantially affect patients' quality of daily life. Insulin-like growth factor 1 receptor (IGF1R) signaling is one of the factors in RA pathogenesis as well as a known regulator of adult neurogenesis. The purpose of this study was to investigate the association between IGF1R signaling and the neurological symptoms in RA. In experimental RA, we demonstrated that arthritis induced enrichment of IBA1+ microglia in the hippocampus. This coincided with inhibitory phosphorylation of insulin receptor substrate 1 (IRS1) and up-regulation of IGF1R in the pyramidal cell layer of the cornus ammoni and in the dentate gyrus, reproducing the molecular features of the IGF1/insulin resistance. The aberrant IGF1R signaling was associated with reduced hippocampal neurogenesis, smaller hippocampus, and increased immobility of RA mice. Inhibition of IGF1R in experimental RA led to a reduction of IRS1 inhibition and partial improvement of neurogenesis. Evaluation of physical functioning and brain imaging in RA patients revealed that enhanced functional disability is linked with smaller hippocampus volume and aberrant IGF1R/IRS1 signaling. These results point to abnormal IGF1R signaling in the brain as a mediator of neurological sequelae in RA and provide support for the potentially reversible nature of hippocampal changes.}, } @article {pmid30509996, year = {2018}, author = {Holder, PJ and Jones, A and Tyler, CR and Cresswell, JE}, title = {Fipronil pesticide as a suspect in historical mass mortalities of honey bees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13033-13038}, doi = {10.1073/pnas.1804934115}, pmid = {30509996}, issn = {1091-6490}, abstract = {Mass mortalities of honey bees occurred in France in the 1990s coincident with the introduction of two agricultural insecticides, imidacloprid and fipronil. Imidacloprid, a neonicotinoid, was widely blamed, but the differential potency of imidacloprid and fipronil has been unclear because of uncertainty over their capacity to bioaccumulate during sustained exposure to trace dietary residues and, thereby, cause time-reinforced toxicity (TRT). We experimentally quantified the toxicity of fipronil and imidacloprid to honey bees and incorporated the observed mortality rates into a demographic simulation of a honey bee colony in an environmentally realistic scenario. Additionally, we evaluated two bioassays from new international guidance for agrochemical regulation, which aim to detect TRT. Finally, we used analytical chemistry (GC-MS) to test for bioaccumulation of fipronil. We found in demographic simulations that only fipronil produced mass mortality in honey bees. In the bioassays, only fipronil caused TRT. GC-MS analysis revealed that virtually all of the fipronil ingested by a honey bee in a single meal was present 6 d later, which suggests that bioaccumulation is the basis of TRT in sustained dietary exposures. We therefore postulate that fipronil, not imidacloprid, caused the mass mortalities of honey bees in France during the 1990s because it is lethal to honey bees in even trace doses due to its capacity to bioaccumulate and generate TRT. Our results provide evidence that recently proposed laboratory bioassays can discriminate harmful bioaccumulative substances and, thereby, address evident shortcomings in a regulatory system that had formerly approved fipronil for agricultural use.}, } @article {pmid30509995, year = {2018}, author = {Chan, CY and Pedley, AM and Kim, D and Xia, C and Zhuang, X and Benkovic, SJ}, title = {Microtubule-directed transport of purine metabolons drives their cytosolic transit to mitochondria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13009-13014}, doi = {10.1073/pnas.1814042115}, pmid = {30509995}, issn = {1091-6490}, support = {R01 GM024129/GM/NIGMS NIH HHS/United States ; R35 GM122487/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {To meet their purine demand, cells activate the de novo purine biosynthetic pathway and transiently cluster the pathway enzymes into metabolons called purinosomes. Recently, we have shown that purinosomes were spatially colocalized with mitochondria and microtubules, yet it remained unclear as to what drives these associations and whether a relationship between them exist. Here, we employed superresolution imaging methods to describe purinosome transit in the context of subcellular localization. Time-resolved imaging of purinosomes showed that these assemblies exhibit directed motion as they move along a microtubule toward mitochondria, where upon colocalization, a change in purinosome motion was observed. A majority of purinosomes colocalized with mitochondria were also deemed colocalized with microtubules. Nocodazole-dependent microtubule depolymerization resulted in a loss in the purinosome-mitochondria colocalization, suggesting that the association of purinosomes with mitochondria is facilitated by microtubule-directed transport, and thereby supporting our notion of an interdependency between these subcellular components in maximizing purine production through the de novo purine biosynthetic pathway.}, } @article {pmid30509994, year = {2018}, author = {Nair, P}, title = {QnAs with David Baker.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13142-13144}, doi = {10.1073/pnas.1819099115}, pmid = {30509994}, issn = {1091-6490}, } @article {pmid30509993, year = {2018}, author = {Bleckert, A and Zhang, C and Turner, MH and Koren, D and Berson, DM and Park, SJH and Demb, JB and Rieke, F and Wei, W and Wong, RO}, title = {GABA release selectively regulates synapse development at distinct inputs on direction-selective retinal ganglion cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12083-E12090}, doi = {10.1073/pnas.1803490115}, pmid = {30509993}, issn = {1091-6490}, support = {P30 EY026878/EY/NEI NIH HHS/United States ; F30 EY025958/EY/NEI NIH HHS/United States ; R01 EY010699/EY/NEI NIH HHS/United States ; F31 EY026288/EY/NEI NIH HHS/United States ; R01 EY012793/EY/NEI NIH HHS/United States ; R01 EY024016/EY/NEI NIH HHS/United States ; R01 EY014454/EY/NEI NIH HHS/United States ; P30 EY001730/EY/NEI NIH HHS/United States ; R01 EY011850/EY/NEI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Synaptic inhibition controls a neuron's output via functionally distinct inputs at two subcellular compartments, the cell body and the dendrites. It is unclear whether the assembly of these distinct inhibitory inputs can be regulated independently by neurotransmission. In the mammalian retina, γ-aminobutyric acid (GABA) release from starburst amacrine cells (SACs) onto the dendrites of on-off direction-selective ganglion cells (ooDSGCs) is essential for directionally selective responses. We found that ooDSGCs also receive GABAergic input on their somata from other amacrine cells (ACs), including ACs containing the vasoactive intestinal peptide (VIP). When net GABAergic transmission is reduced, somatic, but not dendritic, GABAA receptor clusters on the ooDSGC increased in number and size. Correlative fluorescence imaging and serial electron microscopy revealed that these enlarged somatic receptor clusters are localized to synapses. By contrast, selectively blocking vesicular GABA release from either SACs or VIP ACs did not alter dendritic or somatic receptor distributions on the ooDSGCs, showing that neither SAC nor VIP AC GABA release alone is required for the development of inhibitory synapses in ooDSGCs. Furthermore, a reduction in net GABAergic transmission, but not a selective reduction from SACs, increased excitatory drive onto ooDSGCs. This increased excitation may drive a homeostatic increase in ooDSGC somatic GABAA receptors. Differential regulation of GABAA receptors on the ooDSGC's soma and dendrites could facilitate homeostatic control of the ooDSGC's output while enabling the assembly of the GABAergic connectivity underlying direction selectivity to be indifferent to altered transmission.}, } @article {pmid30509992, year = {2018}, author = {Griswold, A}, title = {Profile of Susan Brantley.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12839-12841}, doi = {10.1073/pnas.1506937115}, pmid = {30509992}, issn = {1091-6490}, } @article {pmid30509991, year = {2018}, author = {Fasullo, JT and Nerem, RS}, title = {Altimeter-era emergence of the patterns of forced sea-level rise in climate models and implications for the future.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12944-12949}, doi = {10.1073/pnas.1813233115}, pmid = {30509991}, issn = {1091-6490}, abstract = {The satellite altimeter record has provided an unprecedented database for understanding sea-level rise and has recently reached a major milestone at 25 years in length. A challenge now exists in understanding its broader significance and its consequences for sea-level rise in the coming decades and beyond. A key question is whether the pattern of altimeter-era change is representative of longer-term trends driven by anthropogenic forcing. In this work, two multimember climate ensembles, the Community Earth System Model (CESM) and the Earth System Model Version 2M (ESM2M), are used to estimate patterns of forced change [also known as the forced response (FR)] and their magnitudes relative to internal variability. It is found that the spatial patterns of 1993-2018 trends in the ensembles correlate significantly with the contemporaneous FRs (0.55 ± 0.10 in the CESM and 0.61 ± 0.09 in the ESM2M) and the 1950-2100 FRs (0.43 ± 0.10 in the CESM and 0.51 ± 0.11 in the ESM2M). Unforced runs for each model show such correlations to be extremely unlikely to have arisen by chance, indicating an emergence of both the altimeter-era and long-term FRs and suggesting a similar emergence in nature. Projected patterns of the FR over the coming decades resemble those simulated during the altimeter era, suggesting a continuation of the forced pattern of change in nature in the coming decades. Notably, elevated rates of rise are projected to continue in regions that are susceptible to tropical cyclones, exacerbating associated impacts in a warming climate.}, } @article {pmid30509990, year = {2018}, author = {Yan, R and Zhang, J and Park, HJ and Park, ES and Oh, S and Zheng, H and Junn, E and Voronkov, M and Stock, JB and Mouradian, MM}, title = {Synergistic neuroprotection by coffee components eicosanoyl-5-hydroxytryptamide and caffeine in models of Parkinson's disease and DLB.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12053-E12062}, doi = {10.1073/pnas.1813365115}, pmid = {30509990}, issn = {1091-6490}, support = {R01 NS101134/NS/NINDS NIH HHS/United States ; R33 NS096032/NS/NINDS NIH HHS/United States ; R21 NS095003/NS/NINDS NIH HHS/United States ; R01 NS070898/NS/NINDS NIH HHS/United States ; R21 NS096032/NS/NINDS NIH HHS/United States ; R01 NS073994/NS/NINDS NIH HHS/United States ; R01 AT006868/AT/NCCIH NIH HHS/United States ; P30 NS046593/NS/NINDS NIH HHS/United States ; }, abstract = {Hyperphosphorylated α-synuclein in Lewy bodies and Lewy neurites is a characteristic neuropathological feature of Parkinson's disease (PD) and Dementia with Lewy bodies (DLB). The catalytic subunit of the specific phosphatase, protein phosphatase 2A (PP2A) that dephosphorylates α-synuclein, is hypomethylated in these brains, thereby impeding the assembly of the active trimeric holoenzyme and reducing phosphatase activity. This phosphatase deficiency contributes to the accumulation of hyperphosphorylated α-synuclein, which tends to fibrillize more than unmodified α-synuclein. Eicosanoyl-5-hydroxytryptamide (EHT), a fatty acid derivative of serotonin found in coffee, inhibits the PP2A methylesterase so as to maintain PP2A in a highly active methylated state and mitigates the phenotype of α-synuclein transgenic (SynTg) mice. Considering epidemiologic and experimental evidence suggesting protective effects of caffeine in PD, we sought, in the present study, to test whether there is synergy between EHT and caffeine in models of α-synucleinopathy. Coadministration of these two compounds orally for 6 mo at doses that were individually ineffective in SynTg mice and in a striatal α-synuclein preformed fibril inoculation model resulted in reduced accumulation of phosphorylated α-synuclein, preserved neuronal integrity and function, diminished neuroinflammation, and improved behavioral performance. These indices were associated with increased levels of methylated PP2A in brain tissue. A similar profile of greater PP2A methylation and cytoprotection was found in SH-SY5Y cells cotreated with EHT and caffeine, but not with each compound alone. These findings suggest that these two components of coffee have synergistic effects in protecting the brain against α-synuclein-mediated toxicity through maintenance of PP2A in an active state.}, } @article {pmid30509989, year = {2018}, author = {Mankel, K and Bidelman, GM}, title = {Inherent auditory skills rather than formal music training shape the neural encoding of speech.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13129-13134}, doi = {10.1073/pnas.1811793115}, pmid = {30509989}, issn = {1091-6490}, support = {R01 DC016267/DC/NIDCD NIH HHS/United States ; }, abstract = {Musical training is associated with a myriad of neuroplastic changes in the brain, including more robust and efficient neural processing of clean and degraded speech signals at brainstem and cortical levels. These assumptions stem largely from cross-sectional studies between musicians and nonmusicians which cannot address whether training itself is sufficient to induce physiological changes or whether preexisting superiority in auditory function before training predisposes individuals to pursue musical interests and appear to have similar neuroplastic benefits as musicians. Here, we recorded neuroelectric brain activity to clear and noise-degraded speech sounds in individuals without formal music training but who differed in their receptive musical perceptual abilities as assessed objectively via the Profile of Music Perception Skills. We found that listeners with naturally more adept listening skills ("musical sleepers") had enhanced frequency-following responses to speech that were also more resilient to the detrimental effects of noise, consistent with the increased fidelity of speech encoding and speech-in-noise benefits observed previously in highly trained musicians. Further comparisons between these musical sleepers and actual trained musicians suggested that experience provides an additional boost to the neural encoding and perception of speech. Collectively, our findings suggest that the auditory neuroplasticity of music engagement likely involves a layering of both preexisting (nature) and experience-driven (nurture) factors in complex sound processing. In the absence of formal training, individuals with intrinsically proficient auditory systems can exhibit musician-like auditory function that can be further shaped in an experience-dependent manner.}, } @article {pmid30509988, year = {2018}, author = {Sokolov, I and Dokukin, ME and Kalaparthi, V and Miljkovic, M and Wang, A and Seigne, JD and Grivas, P and Demidenko, E}, title = {Noninvasive diagnostic imaging using machine-learning analysis of nanoresolution images of cell surfaces: Detection of bladder cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12920-12925}, doi = {10.1073/pnas.1816459115}, pmid = {30509988}, issn = {1091-6490}, abstract = {We report an approach in diagnostic imaging based on nanoscale-resolution scanning of surfaces of cells collected from body fluids using a recent modality of atomic force microscopy (AFM), subresonance tapping, and machine-leaning analysis. The surface parameters, which are typically used in engineering to describe surfaces, are used to classify cells. The method is applied to the detection of bladder cancer, which is one of the most common human malignancies and the most expensive cancer to treat. The frequent visual examinations of bladder (cytoscopy) required for follow-up are not only uncomfortable for the patient but a serious cost for the health care system. Our method addresses an unmet need in noninvasive and accurate detection of bladder cancer, which may eliminate unnecessary and expensive cystoscopies. The method, which evaluates cells collected from urine, shows 94% diagnostic accuracy when examining five cells per patient's urine sample. It is a statistically significant improvement (P < 0.05) in diagnostic accuracy compared with the currently used clinical standard, cystoscopy, as verified on 43 control and 25 bladder cancer patients.}, } @article {pmid30509987, year = {2019}, author = {Hassall, C and Billington, J and Sherratt, TN}, title = {Climate-induced phenological shifts in a Batesian mimicry complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {116}, number = {3}, pages = {929-933}, doi = {10.1073/pnas.1813367115}, pmid = {30509987}, issn = {1091-6490}, abstract = {Climate-induced changes in spatial and temporal occurrence of species, as well as species traits such as body size, each have the potential to decouple symbiotic relationships. Past work has focused primarily on direct interactions, particularly those between predators and prey and between plants and pollinators, but studies have rarely demonstrated significant fitness costs to the interacting, coevolving organisms. Here, we demonstrate that changing phenological synchrony in the latter part of the 20th century has different fitness outcomes for the actors within a Batesian mimicry complex, where predators learn to differentiate harmful "model" organisms (stinging Hymenoptera) from harmless "mimics" (hoverflies, Diptera: Syrphidae). We define the mimetic relationships between 2,352 pairs of stinging Hymenoptera and their Syrphidae mimics based on a large-scale citizen science project and demonstrate that there is no relationship between the phenological shifts of models and their mimics. Using computer game-based experiments, we confirm that the fitness of models, mimics, and predators differs among phenological scenarios, creating a phenologically antagonistic system. Finally, we show that climate change is increasing the proportion of mimetic interactions in which models occur first and reducing mimic-first and random patterns of occurrence, potentially leading to complex fitness costs and benefits across all three actors. Our results provide strong evidence for an overlooked example of fitness consequences from changing phenological synchrony.}, } @article {pmid30509986, year = {2018}, author = {Iwamoto, M and Oiki, S}, title = {Constitutive boost of a K+ channel via inherent bilayer tension and a unique tension-dependent modality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13117-13122}, doi = {10.1073/pnas.1812282115}, pmid = {30509986}, issn = {1091-6490}, abstract = {Molecular mechanisms underlying channel-membrane interplay have been extensively studied. Cholesterol, as a major component of the cell membrane, participates either in specific binding to channels or via modification of membrane physical features. Here, we examined the action of various sterols (cholesterol, epicholesterol, etc.) on a prototypical potassium channel (KcsA). Single-channel current recordings of the KcsA channel were performed in a water-in-oil droplet bilayer (contact bubble bilayer) with a mixed phospholipid composition (azolectin). Upon membrane perfusion of sterols, the activated gate at acidic pH closed immediately, irrespective of the sterol species. During perfusion, we found that the contacting bubbles changed their shapes, indicating alterations in membrane physical features. Absolute bilayer tension was measured according to the principle of surface chemistry, and inherent bilayer tension was ∼5 mN/m. All tested sterols decreased the tension, and the nonspecific sterol action to the channel was likely mediated by the bilayer tension. Purely mechanical manipulation that reduced bilayer tension also closed the gate, whereas the resting channel at neutral pH never activated upon increased tension. Thus, rather than conventional stretch activation, the channel, once ready to activate by acidic pH, changes the open probability through the action of bilayer tension. This constitutes a channel regulating modality by two successive stimuli. In the contact bubble bilayer, inherent bilayer tension was high, and the channel remained boosted. In the cell membrane, resting tension is low, and it is anticipated that the ready-to-activate channel remains closed until bilayer tension reaches a few millinewton/meter during physiological and pathological cellular activities.}, } @article {pmid30509985, year = {2018}, author = {Carpenter, BL and Zhou, W and Madaj, Z and DeWitt, AK and Ross, JP and Grønbæk, K and Liang, G and Clark, SJ and Molloy, PL and Jones, PA}, title = {Mother-child transmission of epigenetic information by tunable polymorphic imprinting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11970-E11977}, doi = {10.1073/pnas.1815005115}, pmid = {30509985}, issn = {1091-6490}, support = {R35 CA209859/CA/NCI NIH HHS/United States ; }, abstract = {Genomic imprinting mediated by DNA methylation restricts gene expression to a single allele determined by parental origin and is not generally considered to be under genetic or environmental influence. Here, we focused on a differentially methylated region (DMR) of approximately 1.9 kb that includes a 101-bp noncoding RNA gene (nc886/VTRNA2-1), which is maternally imprinted in ∼75% of humans. This is unlike other imprinted genes, which demonstrate monoallelic methylation in 100% of individuals. The DMR includes a CTCF binding site on the centromeric side defining the DMR boundary and is flanked by a CTCF binding site on the telomeric side. The centromeric CTCF binding site contains an A/C polymorphism (rs2346018); the C allele is associated with less imprinting. The frequency of imprinting of the nc886 DMR in infants was linked to at least two nongenetic factors, maternal age at delivery and season of conception. In a separate cohort, nc886 imprinting was associated with lower body mass index in children at 5 y of age. Thus, we propose that the imprinting status of the nc886 DMR is "tunable" in that it is associated with maternal haplotype and prenatal environment. This provides a potential mechanism for transmitting information, with phenotypic consequences, from mother to child.}, } @article {pmid30509984, year = {2018}, author = {Dasgupta, S and Sheehan, TC and Stevens, CF and Navlakha, S}, title = {A neural data structure for novelty detection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13093-13098}, doi = {10.1073/pnas.1814448115}, pmid = {30509984}, issn = {1091-6490}, abstract = {Novelty detection is a fundamental biological problem that organisms must solve to determine whether a given stimulus departs from those previously experienced. In computer science, this problem is solved efficiently using a data structure called a Bloom filter. We found that the fruit fly olfactory circuit evolved a variant of a Bloom filter to assess the novelty of odors. Compared with a traditional Bloom filter, the fly adjusts novelty responses based on two additional features: the similarity of an odor to previously experienced odors and the time elapsed since the odor was last experienced. We elaborate and validate a framework to predict novelty responses of fruit flies to given pairs of odors. We also translate insights from the fly circuit to develop a class of distance- and time-sensitive Bloom filters that outperform prior filters when evaluated on several biological and computational datasets. Overall, our work illuminates the algorithmic basis of an important neurobiological problem and offers strategies for novelty detection in computational systems.}, } @article {pmid30509983, year = {2018}, author = {Zella, D and Curreli, S and Benedetti, F and Krishnan, S and Cocchi, F and Latinovic, OS and Denaro, F and Romerio, F and Djavani, M and Charurat, ME and Bryant, JL and Tettelin, H and Gallo, RC}, title = {Mycoplasma promotes malignant transformation in vivo, and its DnaK, a bacterial chaperon protein, has broad oncogenic properties.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12005-E12014}, doi = {10.1073/pnas.1815660115}, pmid = {30509983}, issn = {1091-6490}, support = {UL1 GM118973/GM/NIGMS NIH HHS/United States ; }, abstract = {We isolated a strain of human mycoplasma that promotes lymphomagenesis in SCID mice, pointing to a p53-dependent mechanism similar to lymphomagenesis in uninfected p53-/- SCID mice. Additionally, mycoplasma infection in vitro reduces p53 activity. Immunoprecipitation of p53 in mycoplasma-infected cells identified several mycoplasma proteins, including DnaK, a member of the Hsp70 chaperon family. We focused on DnaK because of its ability to interact with proteins. We demonstrate that mycoplasma DnaK interacts with and reduces the activities of human proteins involved in critical cellular pathways, including DNA-PK and PARP1, which are required for efficient DNA repair, and binds to USP10 (a key p53 regulator), impairing p53-dependent anticancer functions. This also reduced the efficacy of anticancer drugs that depend on p53 to exert their effect. mycoplasma was detected early in the infected mice, but only low copy numbers of mycoplasma DnaK DNA sequences were found in some primary and secondary tumors, pointing toward a hit-and-run/hide mechanism of transformation. Uninfected bystander cells took up exogenous DnaK, suggesting a possible paracrine function in promoting malignant transformation, over and above cells infected with the mycoplasma. Phylogenetic amino acid analysis shows that other bacteria associated with human cancers have similar DnaKs, consistent with a common mechanism of cellular transformation mediated through disruption of DNA-repair mechanisms, as well as p53 dysregulation, that also results in cancer-drug resistance. This suggests that the oncogenic properties of certain bacteria are DnaK-mediated.}, } @article {pmid30509982, year = {2018}, author = {Bebbington, AJ and Humphreys Bebbington, D and Sauls, LA and Rogan, J and Agrawal, S and Gamboa, C and Imhof, A and Johnson, K and Rosa, H and Royo, A and Toumbourou, T and Verdum, R}, title = {Resource extraction and infrastructure threaten forest cover and community rights.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13164-13173}, doi = {10.1073/pnas.1812505115}, pmid = {30509982}, issn = {1091-6490}, abstract = {Mineral and hydrocarbon extraction and infrastructure are increasingly significant drivers of forest loss, greenhouse gas emissions, and threats to the rights of forest communities in forested areas of Amazonia, Indonesia, and Mesoamerica. Projected investments in these sectors suggest that future threats to forests and rights are substantial, particularly because resource extraction and infrastructure reinforce each other and enable population movements and agricultural expansion further into the forest. In each region, governments have made framework policy commitments to national and cross-border infrastructure integration, increased energy production, and growth strategies based on further exploitation of natural resources. This reflects political settlements among national elites that endorse resource extraction as a pathway toward development. Regulations that protect forests, indigenous and rural peoples' lands, and conservation areas are being rolled back or are under threat. Small-scale gold mining has intensified in specific locations and also has become a driver of deforestation and degradation. Forest dwellers' perceptions of insecurity have increased, as have documented homicides of environmental activists. To explain the relationships among extraction, infrastructure, and forests, this paper combines a geospatial analysis of forest loss overlapped with areas of potential resource extraction, interviews with key informants, and feedback from stakeholder workshops. The increasing significance of resource extraction and associated infrastructure as drivers of forest loss and rights violations merits greater attention in the empirical analyses and conceptual frameworks of Sustainability Science.}, } @article {pmid30509981, year = {2018}, author = {Schmidt, RR and Fulda, M and Paul, MV and Anders, M and Plum, F and Weits, DA and Kosmacz, M and Larson, TR and Graham, IA and Beemster, GTS and Licausi, F and Geigenberger, P and Schippers, JH and van Dongen, JT}, title = {Low-oxygen response is triggered by an ATP-dependent shift in oleoyl-CoA in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12101-E12110}, doi = {10.1073/pnas.1809429115}, pmid = {30509981}, issn = {1091-6490}, abstract = {Plant response to environmental stimuli involves integration of multiple signals. Upon low-oxygen stress, plants initiate a set of adaptive responses to circumvent an energy crisis. Here, we reveal how these stress responses are induced by combining (i) energy-dependent changes in the composition of the acyl-CoA pool and (ii) the cellular oxygen concentration. A hypoxia-induced decline of cellular ATP levels reduces LONG-CHAIN ACYL-COA SYNTHETASE activity, which leads to a shift in the composition of the acyl-CoA pool. Subsequently, we show that different acyl-CoAs induce unique molecular responses. Altogether, our data disclose a role for acyl-CoAs acting in a cellular signaling pathway in plants. Upon hypoxia, high oleoyl-CoA levels provide the initial trigger to release the transcription factor RAP2.12 from its interaction partner ACYL-COA BINDING PROTEIN at the plasma membrane. Subsequently, according to the N-end rule for proteasomal degradation, oxygen concentration-dependent stabilization of the subgroup VII ETHYLENE-RESPONSE FACTOR transcription factor RAP2.12 determines the level of hypoxia-specific gene expression. This research unveils a specific mechanism activating low-oxygen stress responses only when a decrease in the oxygen concentration coincides with a drop in energy.}, } @article {pmid30509980, year = {2018}, author = {Wälti, MA and Steiner, J and Meng, F and Chung, HS and Louis, JM and Ghirlando, R and Tugarinov, V and Nath, A and Clore, GM}, title = {Probing the mechanism of inhibition of amyloid-β(1-42)-induced neurotoxicity by the chaperonin GroEL.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11924-E11932}, doi = {10.1073/pnas.1817477115}, pmid = {30509980}, issn = {1091-6490}, abstract = {The human chaperonin Hsp60 is thought to play a role in the progression of Alzheimer's disease by mitigating against intracellular β-amyloid stress. Here, we show that the bacterial homolog GroEL (51% sequence identity) reduces the neurotoxic effects of amyloid-β(1-42) (Aβ42) on human neural stem cell-derived neuronal cultures. To understand the mechanism of GroEL-mediated abrogation of neurotoxicity, we studied the interaction of Aβ42 with GroEL using a variety of biophysical techniques. Aβ42 binds to GroEL as a monomer with a lifetime of ∼1 ms, as determined from global analysis of multiple relaxation-based NMR experiments. Dynamic light scattering demonstrates that GroEL dissolves small amounts of high-molecular-weight polydisperse aggregates present in fresh soluble Aβ42 preparations. The residue-specific transverse relaxation rate profile for GroEL-bound Aβ42 reveals the presence of three anchor-binding regions (residues 16-21, 31-34, and 40-41) located within the hydrophobic GroEL-consensus binding sequences. Single-molecule FRET analysis of Aβ42 binding to GroEL results in no significant change in the FRET efficiency of a doubly labeled Aβ42 construct, indicating that Aβ42 samples a random coil ensemble when bound to GroEL. Finally, GroEL substantially slows down the disappearance of NMR visible Aβ42 species and the appearance of Aβ42 protofibrils and fibrils as monitored by electron and atomic force microscopies. The latter observations correlate with the effect of GroEL on the time course of Aβ42-induced neurotoxicity. These data provide a physical basis for understanding how Hsp60 may serve to slow down the progression of Alzheimer's disease.}, } @article {pmid30509979, year = {2018}, author = {Gómez-García, PA and Garbacik, ET and Otterstrom, JJ and Garcia-Parajo, MF and Lakadamyali, M}, title = {Excitation-multiplexed multicolor superresolution imaging with fm-STORM and fm-DNA-PAINT.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12991-12996}, doi = {10.1073/pnas.1804725115}, pmid = {30509979}, issn = {1091-6490}, abstract = {Recent advancements in single-molecule-based superresolution microscopy have made it possible to visualize biological structures with unprecedented spatial resolution. Determining the spatial coorganization of these structures within cells under physiological and pathological conditions is an important biological goal. This goal has been stymied by the current limitations of carrying out superresolution microscopy in multiple colors. Here, we develop an approach for simultaneous multicolor superresolution imaging which relies solely on fluorophore excitation, rather than fluorescence emission properties. By modulating the intensity of the excitation lasers at different frequencies, we show that the color channel can be determined based on the fluorophore's response to the modulated excitation. We use this frequency multiplexing to reduce the image acquisition time of multicolor superresolution DNA-PAINT while maintaining all its advantages: minimal color cross-talk, minimal photobleaching, maximal signal throughput, ability to maintain the fluorophore density per imaged color, and ability to use the full camera field of view. We refer to this imaging modality as "frequency multiplexed DNA-PAINT," or fm-DNA-PAINT for short. We also show that frequency multiplexing is fully compatible with STORM superresolution imaging, which we term fm-STORM. Unlike fm-DNA-PAINT, fm-STORM is prone to color cross-talk. To overcome this caveat, we further develop a machine-learning algorithm to correct for color cross-talk with more than 95% accuracy, without the need for prior information about the imaged structure.}, } @article {pmid30509978, year = {2018}, author = {Kim, SC and O'Flaherty, DK and Zhou, L and Lelyveld, VS and Szostak, JW}, title = {Inosine, but none of the 8-oxo-purines, is a plausible component of a primordial version of RNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13318-13323}, doi = {10.1073/pnas.1814367115}, pmid = {30509978}, issn = {1091-6490}, abstract = {The emergence of primordial RNA-based life would have required the abiotic synthesis of nucleotides, and their participation in nonenzymatic RNA replication. Although considerable progress has been made toward potentially prebiotic syntheses of the pyrimidine nucleotides (C and U) and their 2-thio variants, efficient routes to the canonical purine nucleotides (A and G) remain elusive. Reported syntheses are low yielding and generate a large number of undesired side products. Recently, a potentially prebiotic pathway to 8-oxo-adenosine and 8-oxo-inosine has been demonstrated, raising the question of the suitability of the 8-oxo-purines as substrates for prebiotic RNA replication. Here we show that the 8-oxo-purine nucleotides are poor substrates for nonenzymatic RNA primer extension, both as activated monomers and when present in the template strand; their presence at the end of a primer also strongly reduces the rate and fidelity of primer extension. To provide a proper comparison with 8-oxo-inosine, we also examined primer extension reactions with inosine, and found that inosine exhibits surprisingly rapid and accurate nonenzymatic RNA copying. We propose that inosine, which can be derived from adenosine by deamination, could have acted as a surrogate for G in the earliest stages of the emergence of life.}, } @article {pmid30509977, year = {2018}, author = {Qiu, W and Fu, Z and Xu, GG and Grassucci, RA and Zhang, Y and Frank, J and Hendrickson, WA and Guo, Y}, title = {Structure and activity of lipid bilayer within a membrane-protein transporter.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12985-12990}, doi = {10.1073/pnas.1812526115}, pmid = {30509977}, issn = {1091-6490}, support = {P41 GM116799/GM/NIGMS NIH HHS/United States ; R01 GM029169/GM/NIGMS NIH HHS/United States ; P41 GM103310/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 GM107462/GM/NIGMS NIH HHS/United States ; S10 OD019994/OD/NIH HHS/United States ; }, abstract = {Membrane proteins function in native cell membranes, but extraction into isolated particles is needed for many biochemical and structural analyses. Commonly used detergent-extraction methods destroy naturally associated lipid bilayers. Here, we devised a detergent-free method for preparing cell-membrane nanoparticles to study the multidrug exporter AcrB, by cryo-EM at 3.2-Å resolution. We discovered a remarkably well-organized lipid-bilayer structure associated with transmembrane domains of the AcrB trimer. This bilayer patch comprises 24 lipid molecules; inner leaflet chains are packed in a hexagonal array, whereas the outer leaflet has highly irregular but ordered packing. Protein side chains interact with both leaflets and participate in the hexagonal pattern. We suggest that the lipid bilayer supports and harmonizes peristaltic motions through AcrB trimers. In AcrB D407A, a putative proton-relay mutant, lipid bilayer buttresses protein interactions lost in crystal structures after detergent-solubilization. Our detergent-free system preserves lipid-protein interactions for visualization and should be broadly applicable.}, } @article {pmid30509976, year = {2018}, author = {Viegas, J}, title = {Profile of Akiko Iwasaki.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12544-12546}, doi = {10.1073/pnas.1818903115}, pmid = {30509976}, issn = {1091-6490}, } @article {pmid30509975, year = {2018}, author = {Criglar, JM and Anish, R and Hu, L and Crawford, SE and Sankaran, B and Prasad, BVV and Estes, MK}, title = {Phosphorylation cascade regulates the formation and maturation of rotaviral replication factories.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12015-E12023}, doi = {10.1073/pnas.1717944115}, pmid = {30509975}, issn = {1091-6490}, support = {P30 GM124169/GM/NIGMS NIH HHS/United States ; R01 AI080656/AI/NIAID NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; R37 AI036040/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; /Howard Hughes Medical Institute/Howard Hughes Medical Institute/United States ; }, abstract = {The rotavirus (RV) genome is replicated and packaged into virus progeny in cytoplasmic inclusions called viroplasms, which require interactions between RV nonstructural proteins NSP2 and NSP5. How viroplasms form remains unknown. We previously found two forms of NSP2 in RV-infected cells: a cytoplasmically dispersed dNSP2, which interacts with hypophosphorylated NSP5; and a viroplasm-specific vNSP2, which interacts with hyperphosphorylated NSP5. Other studies report that CK1α, a ubiquitous cellular kinase, hyperphosphorylates NSP5, but requires NSP2 for reasons that are unclear. Here we show that silencing CK1α in cells before RV infection resulted in (i) >90% decrease in RV replication, (ii) disrupted vNSP2 and NSP5 interaction, (iii) dispersion of vNSP2 throughout the cytoplasm, and (iv) reduced vNSP2 protein levels. Together, these data indicate that CK1α directly affects NSP2. Accordingly, an in vitro kinase assay showed that CK1α phosphorylates serine 313 of NSP2 and triggers NSP2 octamers to form a lattice structure as demonstrated by crystallographic analysis. Additionally, a dual-specificity autokinase activity for NSP2 was identified and confirmed by mass spectrometry. Together, our studies show that phosphorylation of NSP2 involving CK1α controls viroplasm assembly. Considering that CK1α plays a role in the replication of other RNA viruses, similar phosphorylation-dependent mechanisms may exist for other virus pathogens that require cytoplasmic virus factories for replication.}, } @article {pmid30509974, year = {2018}, author = {Slotznick, SP and Swanson-Hysell, NL and Sperling, EA}, title = {Oxygenated Mesoproterozoic lake revealed through magnetic mineralogy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12938-12943}, doi = {10.1073/pnas.1813493115}, pmid = {30509974}, issn = {1091-6490}, abstract = {Terrestrial environments have been suggested as an oxic haven for eukaryotic life and diversification during portions of the Proterozoic Eon when the ocean was dominantly anoxic. However, iron speciation and Fe/Al data from the ca. 1.1-billion-year-old Nonesuch Formation, deposited in a large lake and bearing a diverse assemblage of early eukaryotes, are interpreted to indicate persistently anoxic conditions. To shed light on these distinct hypotheses, we analyzed two drill cores spanning the transgression into the lake and its subsequent shallowing. While the proportion of highly reactive to total iron (FeHR/FeT) is consistent through the sediments and typically in the range taken to be equivocal between anoxic and oxic conditions, magnetic experiments and petrographic data reveal that iron exists in three distinct mineral assemblages resulting from an oxycline. In the deepest waters, reductive dissolution of iron oxides records an anoxic environment. However, the remainder of the sedimentary succession has iron oxide assemblages indicative of an oxygenated environment. At intermediate water depths, a mixed-phase facies with hematite and magnetite indicates low oxygen conditions. In the shallowest waters of the lake, nearly every iron oxide has been oxidized to its most oxidized form, hematite. Combining magnetics and textural analyses results in a more nuanced understanding of ambiguous geochemical signals and indicates that for much of its temporal duration, and throughout much of its water column, there was oxygen in the waters of Paleolake Nonesuch.}, } @article {pmid30509973, year = {2018}, author = {Liu, C and Sun, L and Yang, J and Liu, T and Yang, Y and Kim, SM and Ou, X and Wang, Y and Sun, L and Zaidi, M and New, MI and Yuen, T and Guo, Q}, title = {FSIP1 regulates autophagy in breast cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13075-13080}, doi = {10.1073/pnas.1809681115}, pmid = {30509973}, issn = {1091-6490}, support = {R01 AR065932/AR/NIAMS NIH HHS/United States ; R01 AR067066/AR/NIAMS NIH HHS/United States ; }, abstract = {Fibrous sheath interacting protein 1 (FSIP1) is a cancer antigen expressed in the majority of breast cancer tissues and is associated with poor prognosis. However, the role of FSIP1 in the progression and drug sensitivity of triple-negative breast cancer (TNBC) has not been explored. Here, we show that FSIP1 deficiency by shRNA-mediated knockdown or CRISPR-Cas9-mediated knockout significantly inhibits the proliferation and invasion of TNBC cells and impairs chemotherapy-induced growth inhibition in vivo. Computational modeling predicted that FSIP1 binds to ULK1, and this was established by coimmunoprecipitation. FSIP1 deficiency promoted autophagy, enhanced AMP-activated protein kinase (AMPK) signaling, and decreased mechanistic target of rapamycin (mTOR) and Wnt/β-catenin activity. In contrast, knockdown of AMPK or inhibition of autophagy restored the sensitivity to chemotherapy drugs in TNBC cells. Our findings uncover a role of FSIP1 as well as mechanisms underlying FSIP1 action in drug sensitivity and may, therefore, aid in design of TNBC therapies.}, } @article {pmid30509972, year = {2018}, author = {Bjerregaard, VA and Garribba, L and McMurray, CT and Hickson, ID and Liu, Y}, title = {Folate deficiency drives mitotic missegregation of the human FRAXA locus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13003-13008}, doi = {10.1073/pnas.1808377115}, pmid = {30509972}, issn = {1091-6490}, support = {R01 NS060115/NS/NINDS NIH HHS/United States ; P01 CA092584/CA/NCI NIH HHS/United States ; }, abstract = {The instability of chromosome fragile sites is implicated as a causative factor in several human diseases, including cancer [for common fragile sites (CFSs)] and neurological disorders [for rare fragile sites (RFSs)]. Previous studies have indicated that problems arising during DNA replication are the underlying source of this instability. Although the role of replication stress in promoting instability at CFSs is well documented, much less is known about how the fragility of RFSs arises. Many RFSs, as exemplified by expansion of a CGG trinucleotide repeat sequence in the fragile X syndrome-associated FRAXA locus, exhibit fragility in response to folate deficiency or other forms of "folate stress." We hypothesized that such folate stress, through disturbing the replication program within the pathologically expanded repeats within FRAXA, would lead to mitotic abnormalities that exacerbate locus instability. Here, we show that folate stress leads to a dramatic increase in missegregation of FRAXA coupled with the formation of single-stranded DNA bridges in anaphase and micronuclei that contain the FRAXA locus. Moreover, chromosome X aneuploidy is seen when these cells are exposed to folate deficiency for an extended period. We propose that problematic FRAXA replication during interphase leads to a failure to disjoin the sister chromatids during anaphase. This generates further instability not only at FRAXA itself but also of chromosome X. These data have wider implications for the effects of folate deficiency on chromosome instability in human cells.}, } @article {pmid30509927, year = {2018}, author = {Brum, M and López, JG and Asbjornsen, H and Licata, J and Pypker, T and Sanchez, G and Oliveira, RS}, title = {Correction to 'ENSO effects on the transpiration of eastern Amazon trees'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0551}, pmid = {30509927}, issn = {1471-2970}, } @article {pmid30509926, year = {2018}, author = {Bogart, SJ and Azizishirazi, A and Pyle, GG}, title = {Challenges and future prospects for developing Ca and Mg water quality guidelines: a meta-analysis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0364}, pmid = {30509926}, issn = {1471-2970}, abstract = {Anthropogenic activities have the potential to increase water hardness (Ca + Mg) in receiving waters to toxic concentrations, and thus, water quality guidelines (WQG) for Ca and Mg are warranted. However, Ca can modify Mg toxicity in Ca-poor water and additional interactions with other major ions (Na+, K+, HCO3-/CO32-, SO42- and Cl-) may occur, potentially obscuring the water hardness-effect relationship. In a meta-analysis of toxicological studies, we: (i) evaluate the performance of three WQG derivation methods, and (ii) determine the influence of several variables (acute/chronic data, anions, Ca:Mg ratios, non-geographically relevant species) on the models. We find that the most sensitive species- or species sensitivity distribution (SSD)-based WQG derivation methods greatly overestimate water hardness toxicity, particularly if non-resident species are included. Broad-scale implementation of most sensitive species- or SSD-based WQG is impractical because water hardness varies beyond and within the regional scale. Anion type does not affect water hardness toxicity across species, but the Ca : Mg ratio is toxicologically relevant, underscoring the importance of considering ion ratios when developing major ion WQG. Although data supporting formal water hardness WQG are unavailable, we suggest using a two-component background condition approach that supports simultaneous management of water hardness and Ca : Mg ratio, and WQG that are applicable beyond the regional scale.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509925, year = {2018}, author = {Venâncio, C and Castro, BB and Ribeiro, R and Antunes, SC and Abrantes, N and Soares, AMVM and Lopes, I}, title = {Sensitivity of freshwater species under single and multigenerational exposure to seawater intrusion.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0252}, pmid = {30509925}, issn = {1471-2970}, abstract = {Salinization of coastal freshwater ecosystems is already occurring in some regions of the world. This phenomenon raises serious concerns on the protection of coastal freshwater ecosystems, since many of them support and shelter a large number of species and are considered hotspots of biodiversity. This work intended to assess the adverse effects that salinization, caused by the intrusion of seawater (SW), may pose to freshwater organisms. In this study, three specific goals were addressed: (i) to assess if sodium chloride (NaCl) may be used as a surrogate of natural SW at early-stages of risk assessment; (ii) to identify the most sensitive freshwater species to salinity NaCl; and (iii) to determine if increased tolerance to salinity may be acquired after multigenerational exposure to low levels of salinization (induced with NaCl). A total of 12 standard monospecific bioassays were carried out by exposing organisms from different taxonomic groups (Cyanobacteria: one species, Tracheophyta: two species, Rotifera: one species, Arthropoda: two species and Mollusca: one species) to a series of concentrations of NaCl (ranging from 0.95 to 22.8 mS cm-1) or dilutions of SW (ranging from 1.70 to 52.3 mS cm-1). In general, NaCl exerted similar or higher toxicity than SW, both at lethal and sublethal levels, suggesting that it may be proposed as a protective surrogate of SW for first tiers of salinization risk assessment. Among all tested species, the cyanobacterium Cylindrospermopsis raciborskii, the daphnid Daphnia longispina and the rotifer Brachionus plicatilis were the most sensitive taxa to salinization (EC50 ≤ 4.38 mS cm-1). Given their position at the basis of the food web, it is suggested that small increments of salinity may be enough to induce structural changes in freshwater communities or induce changes in trophic relations. No clear evidences of increased tolerance after multigenerational exposure to low levels of salinity were found.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509924, year = {2018}, author = {Pereira, CS and Lopes, I and Abrantes, I and Sousa, JP and Chelinho, S}, title = {Salinization effects on coastal ecosystems: a terrestrial model ecosystem approach.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0251}, pmid = {30509924}, issn = {1471-2970}, abstract = {In coastal areas, intrusion/irrigation with seawater can threaten biodiversity along with crop yields, and the leaching of salts from areas affected by these processes can increase the salinity of water bodies nearby. The aims of this study were to evaluate the effects of salinization on coastal soil ecosystems due to saline intrusion/irrigation. Terrestrial model ecosystems were used to simulate two soil salinization scenarios: (i) seawater intrusion and irrigation with distilled water and (ii) seawater intrusion and irrigation with saline water. Three sampling periods were established: T0-after acclimation period; T1-salinization effects; and T2-populations' recovery. In each sampling period, the abundance of nematodes, enchytraeids, springtails, mites and earthworms, and plant biomass were measured. Immediate negative effects on enchytraeid abundance were detected, especially at the higher level of saltwater via intrusion+irrigation. Eight weeks after the cessation of saline irrigation, the abundance of enchytraeids fully recovered, and some delayed effects were observed in earthworm abundance and plant biomass, especially at the higher soil conductivity level. The observed low capacity of soil to retain salts suggests that, particularly at high soil conductivities, nearby freshwater bodies can also be endangered. Under saline conditions similar to the ones assayed, survival of some soil communities can be threatened, leading to the loss of biodiversity.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509923, year = {2018}, author = {Jackson, JK and Funk, DH}, title = {Temperature affects acute mayfly responses to elevated salinity: implications for toxicity of road de-icing salts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0081}, pmid = {30509923}, issn = {1471-2970}, abstract = {Salinity in freshwater ecosystems has increased significantly at numerous locations throughout the world, and this increase often reflects the use or production of salts from road de-icing, mining/oil and gas drilling activities, or agricultural production. When related to de-icing salts, highest salinity often occurs in winter when water temperature is often low relative to mean annual temperature at a site. Our study examined acute (96 h) responses to elevated salinity (NaCl) concentrations at five to seven temperature treatments (5-25°C) for four mayfly species (Baetidae: Neocloeon triangulifer, Procloeon fragile; Heptageniidae: Maccaffertium modestum; Leptophlebiidae: Leptophlebia cupida) that are widely distributed across eastern North America. Based on acute LC50s at 20°C, P. fragile was most sensitive (LC50 = 767 mg l-1, 1447 µS cm-1), followed by N. triangulifer (2755 mg l-1, 5104 µS cm-1), M. modestum (2760 mg l-1, 5118 µS cm-1) and L. cupida (4588 mg l-1, 8485 µS cm-1). Acute LC50s decreased as temperature increased for all four species (n = 5-7, R2 = 0.65-0.88, p = 0.052-0.002). Thus, acute salt toxicity is strongly temperature dependent for the mayfly species we tested, which suggests that brief periods of elevated salinity during cold seasons or in colder locations may be ecologically less toxic than predicted by standard 20 or 25°C laboratory bioassays.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509922, year = {2018}, author = {Entrekin, SA and Clay, NA and Mogilevski, A and Howard-Parker, B and Evans-White, MA}, title = {Multiple riparian-stream connections are predicted to change in response to salinization.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0042}, pmid = {30509922}, issn = {1471-2970}, abstract = {Secondary freshwater salinization, a common anthropogenic alteration, has detrimental, lethal and sub-lethal effects on aquatic biota. Ions from secondary salinization can become toxic to terrestrial and aquatic organisms when exposed to salinized runoff that causes periodic high-concentration pulses. Gradual, low-level (less than 1000 ppm salinity) increases in salt concentrations are also commonly documented in regions with urbanization, agriculture, drilling and mining. Despite widespread low-level salt increases, little is known about the biological and ecological consequences in coupled riparian-stream systems. Recent research indicates lethal and even sub-lethal levels of ions can subsidize or stress microbial decomposer and macroinvertebrate detritivores that could lead to alterations of three riparian-stream pathways: (i) salinized runoff that changes microbial decomposer and macroinvertebrate detritivore and algae performance leading to changes in composition and processing of detrital pools; (ii) riparian plant salt uptake and altered litter chemistry, and litterfall for riparian and aquatic detritivores and their subsequent enrichment, stimulating decomposition rates and production of dissolved and fine organic matter; and (iii) salt consumption in salinized soils could increase riparian detritivore growth, decomposition and dissolved organic matter production. Subsidy-stress and reciprocal flows in coupled riparian-stream connections provide frameworks to identify the extent and magnitude of changes in detrital processing from salinization.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509921, year = {2018}, author = {Estévez, E and Rodríguez-Castillo, T and González-Ferreras, AM and Cañedo-Argüelles, M and Barquín, J}, title = {Drivers of spatio-temporal patterns of salinity in Spanish rivers: a nationwide assessment.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0022}, pmid = {30509921}, issn = {1471-2970}, abstract = {The salinization of freshwaters is a global water quality problem that leads to the biological degradation of aquatic ecosystems. However, little is known about the spatial extent of freshwater salinization and the relative contribution of each human activity (e.g. agriculture, urbanization, mining or shale-gas extraction). Here, we investigated environmental factors that explain spatio-temporal patterns of water salinity and examined the causes, the extent and the degree of salinization of Spanish rivers. Results showed a strong variation in water salinity among river typologies and between river reaches in good and poor ecological status according to the Water Framework Directive. The variation in water salinity was largely explained by a combination of natural (i.e. climate and geology) and anthropogenic (i.e. land use) factors. By contrast, land use factors as urbanization and agriculture were the main drivers of salinization, which affected more than one quarter of the rivers and streams in Spain, especially those in the most arid regions (central and southern regions) and in the main courses of the largest rivers such as the Ebro, Douro and Tajo rivers. The information provided here can be relevant to set priority regions and actions to ameliorate freshwater salinization.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509920, year = {2018}, author = {Kefford, BJ}, title = {Why are mayflies (Ephemeroptera) lost following small increases in salinity? Three conceptual osmophysiological hypotheses.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0021}, pmid = {30509920}, issn = {1471-2970}, abstract = {The salinity of many freshwaters is increasing globally as a result of human activities. Associated with this increase in salinity are losses of Ephemeroptera (mayfly) abundance and richness. The salinity concentrations at which Ephemeroptera decline in nature are lower than their internal salinity or haemolymph osmolality. Many species also suffer substantial mortality in single species laboratory toxicity tests at salinities lower than their internal salinity. These findings are problematic as conventional osmoregulation theory suggests that freshwater animals should not experience stress where external osmolality is greater than haemolymph osmolality. Here I explore three hypotheses to explain salt sensitivity in Ephemeroptera. These conceptual hypotheses are based on the observations that as the external sodium ion (Na+) concentration increases so does the Na+ turnover rate (both uptake and elimination rates increase). Sulphate ([Formula: see text]) uptake in mayflies also increases with increasing external [Formula: see text] although, unlike Na+, its rate of increase decreases with increasing external [Formula: see text] The first hypothesis is premised on ion turnover being energetically costly. The first hypothesis proposes that individuals must devote a greater proportion of their energy to ion homeostasis at the expense of other uses including growth and development. Lethal levels of salinity presumably result from individuals not being able to devote enough energy to maintain ion homeostasis without critical loss of other vital functions. The second hypothesis is premised on the uptake of Na+ exchanged for (an outgoing) H+, leading to (localized) loss of pH regulation. The third hypothesis is premised on localized Na+ toxicity or poisoning with increased Na turnover as salinity increases. None of the proposed hypotheses is without potential problems, yet all are testable, and research effort should be focused at attempting to falsify them.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509919, year = {2018}, author = {Bray, JP and Reich, J and Nichols, SJ and Kon Kam King, G and Mac Nally, R and Thompson, R and O'Reilly-Nugent, A and Kefford, BJ}, title = {Biological interactions mediate context and species-specific sensitivities to salinity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0020}, pmid = {30509919}, issn = {1471-2970}, abstract = {Toxicants have both sub-lethal and lethal effects on aquatic biota, influencing organism fitness and community composition. However, toxicant effects within ecosystems may be altered by interactions with abiotic and biotic ecosystem components, including biological interactions. Collectively, this generates the potential for toxicant sensitivity to be highly context dependent, with significantly different outcomes in ecosystems than laboratory toxicity tests predict. We experimentally manipulated stream macroinvertebrate communities in 32 mesocosms to examine how communities from a low-salinity site were influenced by interactions with those from a high-salinity site along a gradient of salinity. Relative to those from the low-salinity site, organisms from the high-salinity site were expected to have greater tolerance and fitness at higher salinities. This created the potential for both salinity and tolerant-sensitive organism interactions to influence communities. We found that community composition was influenced by both direct toxicity and tolerant-sensitive organism interactions. Taxon and context-dependent responses included: (i) direct toxicity effects, irrespective of biotic interactions; (ii) effects that were owing to the addition of tolerant taxa, irrespective of salinity; (iii) toxicity dependent on sensitive-tolerant taxa interactions; and (iv) toxic effects that were increased by interactions. Our results reinforce that ecological processes require consideration when examining toxicant effects within ecosystems.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509918, year = {2018}, author = {Schuler, MS and Cañedo-Argüelles, M and Hintz, WD and Dyack, B and Birk, S and Relyea, RA}, title = {Regulations are needed to protect freshwater ecosystems from salinization.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0019}, pmid = {30509918}, issn = {1471-2970}, abstract = {Anthropogenic activities such as mining, agriculture and industrial wastes have increased the rate of salinization of freshwater ecosystems around the world. Despite the known and probable consequences of freshwater salinization, few consequential regulatory standards and management procedures exist. Current regulations are generally inadequate because they are regionally inconsistent, lack legal consequences and have few ion-specific standards. The lack of ion-specific standards is problematic, because each anthropogenic source of freshwater salinization is associated with a distinct set of ions that can present unique social and economic costs. Additionally, the environmental and toxicological consequences of freshwater salinization are often dependent on the occurrence, concentration and ratios of specific ions. Therefore, to protect fresh waters from continued salinization, discrete, ion-specific management and regulatory strategies should be considered for each source of freshwater salinization, using data from standardized, ion-specific monitoring practices. To develop comprehensive monitoring, regulatory, and management guidelines, we recommend the use of co-adaptive, multi-stakeholder approaches that balance environmental, social, and economic costs and benefits associated with freshwater salinization.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509917, year = {2018}, author = {Gonçalves, AL and Carvalho, A and Bärlocher, F and Canhoto, C}, title = {Are fungal strains from salinized streams adapted to salt-rich conditions?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0018}, pmid = {30509917}, issn = {1471-2970}, abstract = {Anthropogenic salinization of freshwater is a global problem with largely unknown consequences for stream functions. We compared the effects of salt addition (6 g l-1 NaCl) in microcosms on leaf mass loss and microbial parameters in single- and multispecies assemblages of fungal strains (Heliscus lugdunensis, HELU; Tetracladium marchalianum, TEMA; Flagellospora curta, FLCU) isolated from a reference (R) or salinized (S) stream. Fungal growth and interactions were also assessed. Salinization inhibited leaf decomposition and fungal biomass, but no differences were observed between species, strains or species combinations. Sporulation rates in monocultures were not affected by added salt, but differed among species (FLCU > HELU > TEMA), with S strains releasing more conidia. Fungal assemblages did not differ significantly in total conidia production (either between strains or medium salt concentration). HELU was the dominant species, which also had highest growth and most pronounced antagonistic behaviour. Fungal species, irrespective of origin, largely maintained their function in salinized streams. Strains from salt-contaminated streams did not trade-off conidial production for vegetative growth at high salt levels. The expected reduction of fungal diversity and potential changes in nutritional litter quality owing to salinization may impact leaf incorporation into secondary production in streams.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509916, year = {2018}, author = {Kaushal, SS and Likens, GE and Pace, ML and Haq, S and Wood, KL and Galella, JG and Morel, C and Doody, TR and Wessel, B and Kortelainen, P and Räike, A and Skinner, V and Utz, R and Jaworski, N}, title = {Novel 'chemical cocktails' in inland waters are a consequence of the freshwater salinization syndrome.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0017}, pmid = {30509916}, issn = {1471-2970}, abstract = {Widespread changes in water temperatures, salinity, alkalinity and pH have been documented in inland waters in North America, which influence ion exchange, weathering rates, chemical solubility and contaminant toxicity. Increasing major ion concentrations from pollution, human-accelerated weathering and saltwater intrusion contribute to multiple ecological stressors such as changing ionic strength and pH and mobilization of chemical mixtures resulting in the freshwater salinization syndrome (FSS). Here, we explore novel combinations of elements, which are transported together as chemical mixtures containing salts, nutrients and metals as a consequence of FSS. First, we show that base cation concentrations have increased in regions primarily in North America and Europe over 100 years. Second, we show interactions between specific conductance, pH, nitrate and metals using data from greater than 20 streams located in different regions of the USA. Finally, salinization experiments and routine monitoring demonstrate mobilization of chemical mixtures of cations, metals and nutrients in 10 streams draining the Washington, DC-Baltimore, MD metropolitan regions. Freshwater salinization mobilizes diverse chemical mixtures influencing drinking water quality, infrastructure corrosion, freshwater CO2 concentrations and biodiversity. Most regulations currently target individual contaminants, but FSS requires managing mobilization of multiple chemical mixtures and interacting ecological stressors as consequences of freshwater salinization.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509915, year = {2018}, author = {Buchwalter, D and Scheibener, S and Chou, H and Soucek, D and Elphick, J}, title = {Are sulfate effects in the mayfly Neocloeon triangulifer driven by the cost of ion regulation?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0013}, pmid = {30509915}, issn = {1471-2970}, abstract = {Elevated major ion concentrations in streams are commonly observed as a consequence of resource extraction, de-icing and other anthropogenic activities. Ecologists report biodiversity losses associated with increasing salinity, with mayflies typically being highly responsive to increases of different major ions. In this study, we evaluated the performance of the mayfly Neocloeon triangulifer reared for its entire larval phase in a gradient of sulfate concentrations. Two natural waters were amended with SO4 as a blend of CaSO4 and MgSO4 and exposures ranged from 5 to 1500 mg l-1 SO4. Survival (per cent successful emergence to the subimago stage) was significantly reduced at the highest SO4 concentration in both waters, while development was significantly delayed at 667 mg l-1 SO4 Final sub-adult body weights were consistent across treatments, except at the highest treatment concentration. Despite evidence for sulfate uptake rates increasing with exposure concentrations and not being saturated at even extremely high SO4 concentrations, total body sulfur changed little in subimagos. Together, these results suggest that elevated SO4 imposes an energetic demand associated with maintaining homeostasis that is manifested primarily as reduced growth rates and associated developmental delays. We identified two genes related to sulfate transport in N. trianguliferThis article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509914, year = {2018}, author = {Hintz, WD and Jones, DK and Relyea, RA}, title = {Evolved tolerance to freshwater salinization in zooplankton: life-history trade-offs, cross-tolerance and reducing cascading effects.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0012}, pmid = {30509914}, issn = {1471-2970}, abstract = {Recent discoveries have documented evolutionary responses to freshwater salinization. We investigated if evolutionary responses to salinization exhibit life-history trade-offs or if they can mitigate ecological impacts such as cascading effects through mechanisms of tolerance and cross-tolerance. We conducted an outdoor mesocosm experiment using populations of Daphnia pulex-a ubiquitous algal grazer-that were either naive or had previously experienced selection to become more tolerant to sodium chloride (NaCl). During the initial phase of population growth, we discovered that evolved tolerance comes at the cost of slower population growth in the absence of salt. We found evolved Daphnia populations maintained a tolerance to NaCl approximately 30 generations after the initial discovery. Evolved tolerance to NaCl also conferred cross-tolerance to a high concentration of CaCl2 (3559 µS cm-1) and a moderate concentration of MgCl2 (967 µS cm-1). A higher concentration of MgCl2 (2188 µS cm-1) overwhelmed the cross-tolerance and killed all Daphnia Tolerance to NaCl did not mitigate NaCl-induced cascades leading to phytoplankton blooms, but cross-tolerance at moderate concentrations of MgCl2 and high concentrations of CaCl2 mitigated such cascading effects caused by these two salts. These discoveries highlight the important interplay between ecology and evolution in understanding the full impacts of freshwater salinization.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509913, year = {2018}, author = {Velasco, J and Gutiérrez-Cánovas, C and Botella-Cruz, M and Sánchez-Fernández, D and Arribas, P and Carbonell, JA and Millán, A and Pallarés, S}, title = {Effects of salinity changes on aquatic organisms in a multiple stressor context.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0011}, pmid = {30509913}, issn = {1471-2970}, abstract = {Under global change, the ion concentration of aquatic ecosystems is changing worldwide. Many freshwater ecosystems are being salinized by anthropogenic salt inputs, whereas many naturally saline ones are being diluted by agricultural drainages. This occurs concomitantly with changes in other stressors, which can result in additive, antagonistic or synergistic effects on organisms. We reviewed experimental studies that manipulated salinity and other abiotic stressors, on inland and transitional aquatic habitats, to (i) synthesize their main effects on organisms' performance, (ii) quantify the frequency of joint effect types across studies and (iii) determine the overall individual and joint effects and their variation among salinity-stressor pairs and organism groups using meta-analyses. Additive effects were slightly more frequent (54%) than non-additive ones (46%) across all the studies (n = 105 responses). However, antagonistic effects were dominant for the stressor pair salinity and toxicants (44%, n = 43), transitional habitats (48%, n = 31) and vertebrates (71%, n = 21). Meta-analyses showed detrimental additive joint effects of salinity and other stressors on organism performance and a greater individual impact of salinity than the other stressors. These results were consistent across stressor pairs and organism types. These findings suggest that strategies to mitigate multiple stressor impacts on aquatic ecosystems should prioritize restoring natural salinity concentrations.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509912, year = {2018}, author = {Berger, E and Frör, O and Schäfer, RB}, title = {Salinity impacts on river ecosystem processes: a critical mini-review.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0010}, pmid = {30509912}, issn = {1471-2970}, abstract = {In many dry parts of the world, salinization of water resources threatens freshwater biodiversity and the livelihood of people. However, ecological impact studies remain scarce. Here, we review field-observations of salinity impacts on ecosystem processes such as leaf decomposition, metabolism, biomass production and nutrient cycling, with a special emphasis on dryland ecosystems. In addition, we discuss the potential linkages of these processes to ecosystem service delivery-the benefits that humans derive from ecosystems-as additional nature conservation arguments and the challenges associated with this endeavour.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509911, year = {2018}, author = {Gutiérrez-Cánovas, C and Sánchez-Fernández, D and Cañedo-Argüelles, M and Millán, A and Velasco, J and Acosta, R and Fortuño, P and Otero, N and Soler, A and Bonada, N}, title = {Do all roads lead to Rome? Exploring community trajectories in response to anthropogenic salinization and dilution of rivers.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0009}, pmid = {30509911}, issn = {1471-2970}, abstract = {Abiotic stress shapes how communities assemble and support ecological functions. However, it remains unclear whether artificially increasing or decreasing stress levels would lead to communities assembling predictably along a single axis of variation or along multiple context-dependent trajectories of change. In response to stress intensity alterations, we hypothesize that a single trajectory of change occurs when trait-based assembly prevails, while multiple trajectories of change arise when dispersal-related processes modify colonization and trait-filtering dynamics. Here, we tested these hypotheses using aquatic macroinvertebrates from rivers exposed to gradients of natural salinity and artificially diluted or salinized ion contents. Our results showed that trait-filtering was important in driving community assembly in natural and diluted rivers, while dispersal-related processes seemed to play a relevant role in response to salinization. Salinized rivers showed novel communities with different trait composition, while natural and diluted communities exhibited similar taxonomic and trait compositional patterns along the conductivity gradient. Our findings suggest that the artificial modification of chemical stressors can result in different biological communities, depending on the direction of the change (salinization or dilution), with trait-filtering, and organism dispersal and colonization dynamics having differential roles in community assembly. The approach presented here provides both empirical and conceptual insights that can help in anticipating the ecological effects of global change, especially for those stressors with both natural and anthropogenic origins.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509910, year = {2018}, author = {Arribas, P and Gutiérrez-Cánovas, C and Botella-Cruz, M and Cañedo-Argüelles, M and Antonio Carbonell, J and Millán, A and Pallarés, S and Velasco, J and Sánchez-Fernández, D}, title = {Insect communities in saline waters consist of realized but not fundamental niche specialists.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0008}, pmid = {30509910}, issn = {1471-2970}, abstract = {Considering how organisms adapt to stress is essential if we are to anticipate biological responses to global change in ecosystems. Communities in stressful environments can potentially be assembled by specialists (i.e. species that only occur in a limited range of environmental conditions) and/or generalist species with wider environmental tolerances. We review the existing literature on the salinity tolerance of aquatic insects previously identified as saline specialists because they were exclusively found in saline habitats, and explore if these saline realized niche specialists are also specialists in their fundamental niches or on the contrary are fundamental niche generalist species confined to the highest salinities they can tolerate. The results suggest that species inhabiting saline waters are generalists in their fundamental niches, with a predominant pattern of high survival in freshwater-low salinity conditions, where their fitness tends to be similar or even higher than in saline waters. Additionally, their performance in freshwater tends to be similar to related strictly freshwater species, so no apparent trade-off of generalization is shown. These results are discussed in the framework of the ecological and evolutionary processes driving community assembly across the osmotic stress gradient, and their potential implications for predicting impacts from saline dilution and freshwater salinization.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509909, year = {2018}, author = {Schulz, CJ and Cañedo-Argüelles, M}, title = {Lost in translation: the German literature on freshwater salinization.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0007}, pmid = {30509909}, issn = {1471-2970}, abstract = {Human activities have globally increased and altered the ion concentration of freshwater ecosystems. The proliferation of potash mines in Germany (especially intense in the early 1900s) constitutes a good example of it. The effluents and runoff coming from potash mines led to extreme salt concentrations (e.g. 72 g l-1 of total salt content, approx. 149 mS cm-1) in surrounding rivers and streams, causing ecosystem degradation (e.g. massive algal blooms and fish kills). This promoted scientific research that was mostly published in German, thereby being neglected by the wide scientific community. Here, the findings of the German literature on freshwater salinization are discussed in the light of current knowledge. German studies revealed that at similar ion concentrations potassium (K+) can be the most toxic ion to freshwater organisms, whereas calcium (Ca2+) could have a toxicity ameliorating effect. Also, they showed that salinization could lead to biodiversity loss, major shifts in the composition of aquatic communities (e.g. dominance of salt-tolerant algae, proliferation of invasive species) and alter organic matter processing. The biological degradation caused by freshwater salinization related to potash mining has important management implications, e.g. it could prevent many European rivers and streams from reaching the good ecological status demanded by the Water Framework Directive. Within this context, German publications show several examples of salinity thresholds and biological indices that could be useful to monitor and regulate salinization (i.e. developing legally enforced salinity and ion-specific standards). They also provide potential management techniques (i.e. brine collection and disposal) and some estimates of the economic costs of freshwater salinization. Overall, the German literature on freshwater salinization provides internationally relevant information that has rarely been cited by the English literature. We suggest that the global editorial and scientific community should take action to make important findings published in non-English literature more widely available.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509908, year = {2018}, author = {Gorostiza, S and Saurí, D}, title = {Naturalizing pollution: a critical social science view on the link between potash mining and salinization in the Llobregat river basin, northeast Spain.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0006}, pmid = {30509908}, issn = {1471-2970}, abstract = {The scientific literature distinguishes between primary or natural and secondary or human-induced salinization. Assessing this distinction is of vital importance to assign liabilities and responsibilities in pollution cases and for designing the best policy and management actions. In this context, actors interested in downplaying the role of certain drivers of human-induced salinization can attempt to neglect its importance by referring to natural salinization, in a similar fashion to other pollution and health-related cases, from tobacco smoke to climate change. Potash mining, which has experienced continued growth during the last decades and is a significant contributor to salinization, is prone to originate such controversies because natural salinization from the saline geological catch can be mixed with salinization produced by mining waste such as brines and mine tailings, thus obscuring the distinction between causes. By reviewing the long-standing social and environmental conflict caused by potash mining in a region of Mediterranean climate-the Llobregat river basin-in this article, we highlight the importance of the impacts of salinization on human health and provide a critical social science perspective on salinization processes.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509907, year = {2018}, author = {Olson, JR}, title = {Predicting combined effects of land use and climate change on river and stream salinity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0005}, pmid = {30509907}, issn = {1471-2970}, abstract = {Agricultural, industrial and urban development have all contributed to increased salinity in streams and rivers, but the likely effects of future development and climate change are unknown. I developed two empirical models to estimate how these combined effects might affect salinity by the end of this century (measured as electrical conductivity, EC). The first model predicts natural background from static (e.g. geology and soils) and dynamic (i.e. climate and vegetation) environmental factors and explained 78% of the variation in EC. I then compared the estimated background EC with current measurements at 2001 sites chosen probabilistically from all conterminous USA streams. EC was more than 50% greater at 34% of these sites. The second model predicts deviation of EC from background as a function of human land use and environmental factors and explained 60% of the variation in alteration from background. I then predicted the effects of climate and land use change on EC at the end of the century by replacing dynamic variables with published projections of future conditions based on the A2 emissions scenario. By the end of the century, the median EC is predicted to increase from 0.319 mS cm-1 to 0.524 mS cm-1 with over 50% of streams having greater than 50% increases in EC and 35% more than doubling their EC. Most of the change is related to increases in human land use, with climate change accounting for only 12% of the increase. In extreme cases, increased salinity may make water unsuitable for human use, but widespread moderate increases are likely a greater threat to stream ecosystems owing to the elimination of low EC habitats.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509906, year = {2018}, author = {Le, TDH and Kattwinkel, M and Schützenmeister, K and Olson, JR and Hawkins, CP and Schäfer, RB}, title = {Predicting current and future background ion concentrations in German surface water under climate change.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0004}, pmid = {30509906}, issn = {1471-2970}, abstract = {Salinization of surface waters is a global environmental issue that can pose a regional risk to freshwater organisms, potentially leading to high environmental and economic costs. Global environmental change including climate and land use change can increase the transport of ions into surface waters. We fit both multiple linear regression (LR) and random forest (RF) models on a large spatial dataset to predict Ca2+ (266 sites), Mg2+ (266 sites), and [Formula: see text] (357 sites) ion concentrations as well as electrical conductivity (EC-a proxy for total dissolved solids with 410 sites) in German running water bodies. Predictions in both types of models were driven by the major factors controlling salinity including geologic and soil properties, climate, vegetation and topography. The predictive power of the two types of models was very similar, with RF explaining 71-76% of the spatial variation in ion concentrations and LR explaining 70-75% of the variance. Mean squared errors for predictions were all smaller than 0.06. The factors most strongly associated with stream ion concentrations varied among models but rock chemistry and climate were the most dominant. The RF model was subsequently used to forecast the changes in EC that were likely to occur for the period of 2070 to 2100 in response to just climate change-i.e. no additional effects of other anthropogenic activities. The future forecasting shows approximately 10% and 15% increases in mean EC for representative concentration pathways 2.6 and 8.5 (RCP2.6 and RCP8.5) scenarios, respectively.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509905, year = {2018}, author = {Hills, KA and Hyne, RV and Kefford, BJ}, title = {Species of freshwater invertebrates that are sensitive to one saline water are mostly sensitive to another saline water but an exception exists.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0003}, pmid = {30509905}, issn = {1471-2970}, abstract = {Coal mining and extraction of methane from coal beds generate effluent with elevated salinity or major ion concentrations. If discharged to freshwater systems, these effluents may have adverse environmental effects. There is a growing body of work on freshwater invertebrates that indicates variation in the proportion of major ions can be more important than salinity when determining toxicity. However, it is not known if saline toxicity in a subset of species is representative of toxicity across all freshwater invertebrates. If patterns derived from a subset of species are representative of all freshwater invertebrates, then we would expect a correlation in the relative sensitivity of these species to multiple saline waters. Here, we determine if there is a correlation between the acute (96 h) lethal toxicity in freshwater invertebrates to synthetic marine salts (SMS) and sodium bicarbonate (NaHCO3) added to dechlorinated Sydney tap water. NaHCO3 is a major component of many coal bed effluents. However, most salinization in Australia exhibits ionic composition similar to seawater, which has very little HCO3- Across all eight species tested, NaHCO3 was 2-50 times more toxic than SMS. We also observed strong correlations in the acute toxicity of seven of the tested species to SMS and NaHCO3 The strongest relationship (LC50 r2 = 0.906) was dependent on the exclusion of one species, Paratya australiensis (Decopoda: Atyidae), which was the most sensitive species tested to NaHCO3, but the second-most tolerant of SMS. We conclude that differences in the toxicity of different proportions of major ions can be similar across a wide range of species. Therefore, a small subset of the invertebrate community can be representative of the whole. However, there are some species, which based on the species tested in the current study appear to be a minority, that respond differently to saline effluent and need to be considered separately. We discuss the implications of this study for the management of saline coal bed waters.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509904, year = {2018}, author = {Cañedo-Argüelles, M and Kefford, B and Schäfer, R}, title = {Salt in freshwaters: causes, effects and prospects - introduction to the theme issue.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1764}, pages = {}, doi = {10.1098/rstb.2018.0002}, pmid = {30509904}, issn = {1471-2970}, abstract = {Humans are globally increasing the salt concentration of freshwaters (i.e. freshwater salinization), leading to significant effects at the population, community and ecosystem level. The present theme issue focuses on priority research questions and delivers results that contribute to shaping the future research agenda on freshwater salinization as well as fostering our capacity to manage salinization. The issue is structured along five topics: (i) the estimation of future salinity and evaluation of the relative contribution of the different drivers; (ii) the physiological responses of organisms to alterations in ion concentrations with a specific focus on the osmophysiology of freshwater insects and the responses of different organisims to seawater intrusion; (iii) the impact of salinization on ecosystem functioning, also considering the connections between riparian and stream ecosystems; (iv) the role of context in moderating the response to salinization. The contributions scrutinise the role of additional stressors, biotic interactions, the identify of the ions and their ratios, as well as of the biogeographic and evolutionary context; and (v) the public discourse on salinization and recommendations for management and regulation. In this paper we introduce the general background of salinization, outline research gaps and report key findings from the contributions to this theme issue.This article is part of the theme issue 'Salt in freshwaters: causes, ecological consequences and future prospects'.}, } @article {pmid30509848, year = {2019}, author = {Kleijn, D and Bommarco, R and Fijen, TPM and Garibaldi, LA and Potts, SG and van der Putten, WH}, title = {Ecological Intensification: Bridging the Gap between Science and Practice.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {2}, pages = {154-166}, doi = {10.1016/j.tree.2018.11.002}, pmid = {30509848}, issn = {1872-8383}, abstract = {There is worldwide concern about the environmental costs of conventional intensification of agriculture. Growing evidence suggests that ecological intensification of mainstream farming can safeguard food production, with accompanying environmental benefits; however, the approach is rarely adopted by farmers. Our review of the evidence for replacing external inputs with ecosystem services shows that scientists tend to focus on processes (e.g., pollination) rather than outcomes (e.g., profits), and express benefits at spatio-temporal scales that are not always relevant to farmers. This results in mismatches in perceived benefits of ecological intensification between scientists and farmers, which hinders its uptake. We provide recommendations for overcoming these mismatches and highlight important additional factors driving uptake of nature-based management practices, such as social acceptability of farming.}, } @article {pmid30509788, year = {2019}, author = {Dong, Z and Alexander, M and Chuck, G}, title = {Understanding Grass Domestication through Maize Mutants.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {118-128}, doi = {10.1016/j.tig.2018.10.007}, pmid = {30509788}, issn = {0168-9525}, abstract = {As an economically important model crop plant, rich in genetic resources, maize has been useful for uncovering the genetic pathways responsible for domestication and plant improvement. However, several of the pathways that have been shown by recent studies to be important for domestication and/or yield in other grasses function differently in maize. In several cases, this unexpectedly wide functional divergence between genes from closely related grasses appears to be due to alternative modes of regulation rather than to simple differences in protein function. This indicates that domestication genes need to be understood within the architecture of the whole genome and the species-specific processes that they influence before they can serve as the foundation to improve plants.}, } @article {pmid30509787, year = {2019}, author = {Fraser, HB}, title = {Improving Estimates of Compensatory cis-trans Regulatory Divergence.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {88}, doi = {10.1016/j.tig.2018.10.003}, pmid = {30509787}, issn = {0168-9525}, } @article {pmid30509563, year = {2018}, author = {Brown, AJP and Gow, NAR and Warris, A and Brown, GD}, title = {Memory in Fungal Pathogens Promotes Immune Evasion, Colonisation, and Infection.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.11.001}, pmid = {30509563}, issn = {1878-4380}, abstract = {By analogy with Pavlov's dogs, certain pathogens have evolved anticipatory behaviours that exploit specific signals in the human host to prepare themselves against imminent host challenges. This adaptive prediction, a type of history-dependent microbial behaviour, represents a primitive form of microbial memory. For fungal pathogens, adaptive prediction helps them circumvent nutritional immunity, protects them against phagocytic killing, and activates immune evasion strategies. We describe how these anticipatory responses, and the contrasting lifestyles and evolutionary trajectories of fungal pathogens, have influenced the evolution of such adaptive behaviours, and how these behaviours affect host colonisation and infection.}, } @article {pmid30509324, year = {2018}, author = {Gebrecherkos, K and Gebremariam, B and Gebeyehu, A and Siyum, H and Kahsay, G and Abay, M}, title = {Unmet need for modern contraception and associated factors among reproductive age group women in Eritrean refugee camps, Tigray, north Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {851}, pmid = {30509324}, issn = {1756-0500}, abstract = {OBJECTIVE: Millions of women want to delay or avoid pregnancy, but they are not using contraception, especially in refugee settings. Due to lack of contraception, one fifth of reproductive age group women suffered from unwanted pregnancy and unsafe abortion, which accounted for 78% of maternal mortality in refugee camps. Therefore, the aim of this study was to assess the prevalence of unmet need for modern contraception and its associated factors among reproductive age group women in Eritrean refugee camps, Tigray, Northern Ethiopia, 2016.

RESULTS: 400 women of reproductive age group interviewed. Prevalence of unmet need for modern contraception in this study was found to be 41.8% (95% CI 36.99%, 46.63%).Respondents' unfavorable attitude towards modern contraceptive methods [AOR = 0.372, 95% CI 0.170, 0.818] and the availability of modern contraceptive methods [AOR = 3.501, 95% CI 1.328, 9.231] were factors significantly associated with unmet need for modern contraception. Respondents' attitude towards modern contraceptive methods and availability of modern contraceptives were independent predictors of unmet need. Governmental and non-governmental organizations should design programs to create behavioral change in women's attitude towards contraceptive use and to secure the availability of contraceptive methods in refugee camp settings.}, } @article {pmid30509321, year = {2018}, author = {Costello, E and Holland, JC and Kirwan, C}, title = {Evaluation of MCQs from MOOCs for common item writing flaws.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {849}, pmid = {30509321}, issn = {1756-0500}, abstract = {OBJECTIVE: There is a dearth of research into the quality of assessments based on Multiple Choice Question (MCQ) items in Massive Open Online Courses (MOOCs). This dataset was generated to determine whether MCQ item writing flaws existed in a selection of MOOC assessments, and to evaluate their prevalence if so. Hence, researchers reviewed MCQs from a sample of MOOCs, using an evaluation protocol derived from the medical health education literature, which has an extensive evidence-base with regard to writing quality MCQ items.

DATA DESCRIPTION: This dataset was collated from MCQ items in 18 MOOCs in the areas of medical health education, life sciences and computer science. Two researchers critically reviewed 204 questions using an evidence-based evaluation protocol. In the data presented, 50% of the MCQs (112) have one or more item writing flaw, while 28% of MCQs (57) contain two or more flaws. Thus, a majority of the MCQs in the dataset violate item-writing guidelines, which mirrors findings of previous research that examined rates of flaws in MCQs in traditional formal educational contexts.}, } @article {pmid30509318, year = {2018}, author = {Stetzik, LA and Sullivan, AW and Patisaul, HB and Cushing, BS}, title = {Novel unconditioned prosocial behavior in prairie voles (Microtus ochrogaster) as a model for empathy.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {852}, pmid = {30509318}, issn = {1756-0500}, support = {ES021233//National Institute of Environmental Health Sciences/ ; }, abstract = {OBJECTIVE: In this study, empathy is quantified using a novel social test. Empathy and prosocial behavior are linked to the expression of oxytocin in humans and rodent models. Specifically, prosocial behavior in prairie voles (Microtus ochrogaster) has been linked to the expression of oxytocin in the paraventricular nucleus of the hypothalamus. The animal's behavior was considered empathic if it spends significantly more time attempting to remove a loos fitting restraint (tether) from the stimulus animal than time in contact with a, simultaneously presented, non-social object similar to the tether. The behavioral data was cross-referenced with the number of neurons expressing oxytocin and arginine vasopressin, as well as the density of dopaminergic neurons (identified by the expression of tyrosine hydroxylase), in the paraventricular nucleus of the hypothalamus. These proteins influence empathic behavior in humans, non-human primates, rats, mice, and prairie voles.

RESULTS: The consistency between neuroanatomical mechanisms linked to empathy, and the durations of time spent engaging in empathic contact, support the prediction that the empathic contact in this test is a distinct prosocial behavior, lacking prior behavioral training or the naturally occurring ethological relevance of other prosocial behaviors, and is a measure of empathy.}, } @article {pmid30509313, year = {2018}, author = {Orish, VN and De-Gaulle, VF and Sanyaolu, AO}, title = {Interpreting rapid diagnostic test (RDT) for Plasmodium falciparum.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {850}, pmid = {30509313}, issn = {1756-0500}, abstract = {OBJECTIVE: Rapid diagnostic tests have been of tremendous help in malaria control in endemic areas, helping in diagnosis and treatment of malaria cases. It is heavily relied upon in many endemic areas where microscopy cannot be obtained. However, caution should be taken in the interpretation of its result in clinical setting due to its limitations and inherent weakness. This paper seeks to present the varying malaria RDT test results, the possible interpretations and explanation of these results common in endemic regions. Published works on malaria RDT studies were identified using the following search terms "malaria RDT in endemic areas", "Plasmodium falciparum and bacterial coinfection" "Plasmodium falciparum RDT test results in children in endemic areas" in Google Scholar and PubMed.

RESULTS: The review results show that RDT positive results in febrile patients can either be true or false positive. True positive, representing either a possible single infection of Plasmodium or a co-infection of bacteria and P. falciparum. False RDT negative results can be seen in febrile patient with P. falciparum infection in prozone effect, Histidine rich protein 2 (HRP2) gene deletion and faulty RDT kits. Hence, a scale up of laboratory facilities especially expert microscopy and other diagnostic tools is imperative.}, } @article {pmid30509239, year = {2018}, author = {Dunker, S and Boho, D and Wäldchen, J and Mäder, P}, title = {Combining high-throughput imaging flow cytometry and deep learning for efficient species and life-cycle stage identification of phytoplankton.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {51}, pmid = {30509239}, issn = {1472-6785}, support = {01LC1319A//Bundesministerium für Bildung und Forschung/ ; 01LC1319B//Bundesministerium für Bildung und Forschung/ ; }, abstract = {BACKGROUND: Phytoplankton species identification and counting is a crucial step of water quality assessment. Especially drinking water reservoirs, bathing and ballast water need to be regularly monitored for harmful species. In times of multiple environmental threats like eutrophication, climate warming and introduction of invasive species more intensive monitoring would be helpful to develop adequate measures. However, traditional methods such as microscopic counting by experts or high throughput flow cytometry based on scattering and fluorescence signals are either too time-consuming or inaccurate for species identification tasks. The combination of high qualitative microscopy with high throughput and latest development in machine learning techniques can overcome this hurdle.

RESULTS: In this study, image based cytometry was used to collect ~ 47,000 images for brightfield and Chl a fluorescence at 60× magnification for nine common freshwater species of nano- and micro-phytoplankton. A deep neuronal network trained on these images was applied to identify the species and the corresponding life cycle stage during the batch cultivation. The results show the high potential of this approach, where species identity and their respective life cycle stage could be predicted with a high accuracy of 97%.

CONCLUSIONS: These findings could pave the way for reliable and fast phytoplankton species determination of indicator species as a crucial step in water quality assessment.}, } @article {pmid30509188, year = {2018}, author = {Fritz, S and Rajaonison, A and Chabrol, O and Raoult, D and Rolain, JM and Merhej, V}, title = {Full-length title: NRPPUR database search and in vitro analysis identify an NRPS-PKS biosynthetic gene cluster with a potential antibiotic effect.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {463}, pmid = {30509188}, issn = {1471-2105}, mesh = {Anti-Bacterial Agents/*chemistry ; Databases, Factual ; Humans ; Multigene Family/*genetics ; Peptide Synthases/*genetics ; }, abstract = {BACKGROUND: Growing concern about the emergence of antibiotic resistance is compelling the pharmaceutical industry to search for new antimicrobial agents. The availability of genome sequences has enabled the development of computational mining as an important tool in the discovery of natural products with antibiotic effect.

RESULTS: NRPPUR (Non-Ribosomal Peptide and Polyketide Urmite) is a new bioinformatic tool that was created to detect polyketides and non-ribosomal peptide gene clusters (PKS and NRPS) in bacterial genomes using the rpsBlast program. The NRPPUR database was constructed locally by assembling all 3505 available sequences of NRPS-PKS that have been identified by in silico approaches to date, with 164 Biosynthetic Gene Clusters (BGCs) derived from the published literature that have demonstrated antimicrobial activity in vitro. The in silico analysis of 49 intestinal human bacterial genomes using the NRPPUR made it possible to identify 91 BGCs including 89 clusters that had never previously been described. On average, intestinal human bacterial genomes devote nearly 0.8% (±1.4% s.d.) of their genome to NRPS/PKS biosynthesis, with Bacillus vallismortis, Streptomyces massiliensis and Bacillus subtilis genomes apportioning 8.4, 3.6 and 3.15% of their genomes, respectively. When using the cross-streak method, S. massiliensis displayed antibacterial activity against many Gram-positive and negative bacteria including methicillin-resistant Staphylococcus aureus (MRSA).

CONCLUSIONS: NRPPUR has proven to be a very useful tool for the primary in silico selection of species with potential antimicrobial activity and human microbiota could be the future source of new antimicrobial discoveries. Further exploration of this and other ecological niches, coupled with high-throughput antibacterial activity screening should be envisaged.}, } @article {pmid30509184, year = {2018}, author = {Myszczyński, K and Górski, P and Ślipiko, M and Sawicki, J}, title = {Sequencing of organellar genomes of Gymnomitrion concinnatum (Jungermanniales) revealed the first exception in the structure and gene order of evolutionary stable liverworts mitogenomes.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {321}, pmid = {30509184}, issn = {1471-2229}, support = {2017/01/X/NZ8/01094//Narodowe Centrum Nauki/ ; 2016/21/B/NZ8/03325//Narodowe Centrum Nauki/ ; 2015/19/B/NZ8/03970//Narodowe Centrum Nauki/ ; }, mesh = {Biological Evolution ; Gene Order/*genetics ; Gene Rearrangement/genetics ; Genome, Chloroplast/*genetics ; Genome, Mitochondrial/*genetics ; Genome, Plant/*genetics ; Hepatophyta/*genetics ; Phylogeny ; }, abstract = {BACKGROUND: Comparative analyses of chloroplast and mitochondrial genomes have shown that organelle genomes in bryophytes evolve slowly. However, in contrast to seed plants, the organellar genomes are yet poorly explored in bryophytes, especially among liverworts. Discovering another organellar genomes of liverwort species by sequencing provides new conclusions on evolution of bryophytes.

RESULTS: In this work, the organellar genomes of Gymnomitrion concinnatum liverwort were sequenced, assembled and annotated for the first time. The chloroplast genome displays, typical for most plants, quadripartite structure containing large single copy region (81,701 bp), two inverted repeat regions (8704 bp each) and small single copy region (20,179 bp). The gene order and content of chloroplast are very similar to other liverworts with minor differences observed. A total number of 739 and 222 RNA editing sites were predicted in chloroplast and mitochondrial genes of G. concinnatum. The mitochondrial genome gene content is also in accordance with liverworts except few alterations such as: intron loss in cox1 and atp1 genes. Nonetheless the analysis revealed that G. concinnatum mitogenome structure and gene order are rearranged in comparison with other mitogenomes of liverworts. The causes underlying such mitogenomic rearrangement were investigated and the probable model of recombination was proposed.

CONCLUSIONS: This study provide the overview of mitochondrial and chloroplast genome structure and gene order diversity of Gymnomitrion concinnatum against the background of known organellar genomes of liverworts. The obtained results cast doubt on the idea that mitogenome structure of early land plants is highly conserved as previous studies suggested. In fact is the very first case of recombination within, evolutionary stable, mitogenomes of liverworts.}, } @article {pmid30509181, year = {2018}, author = {Barba-Espin, G and Glied-Olsen, S and Dzhanfezova, T and Joernsgaard, B and Lütken, H and Müller, R}, title = {Preharvest application of ethephon and postharvest UV-B radiation improve quality traits of beetroot (Beta vulgaris L. ssp. vulgaris) as source of colourant.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {316}, pmid = {30509181}, issn = {1471-2229}, abstract = {BACKGROUND: Betanins have become excellent replacers for artificial red-purple food colourants. Red beet (Beta vulgaris L. spp. vulgaris) known as beetroot, is a rich source of betalains, which major forms are betanin (red to purple) and vulgaxanthin (yellow). Betalains and phenolic compounds are secondary metabolites, accumulation of which is often triggered by elicitors during plant stress responses. In the present study, pre-harvest applications of ethephon (an ethylene-releasing compound) and postharvest UV-B radiation were tested as elicitors of betalains and phenolic compounds in two beetroot cultivars. Their effects on quality parameters were investigated, and the expression of biosynthetic betalain genes in response to ethephon was determined.

RESULTS: Ethephon was applied as foliar spray during the growth of beetroot, resulting in increased betanin (22.5%) and decreased soluble solids contents (9.4%), without detrimental effects on beetroot yield. The most rapid accumulation rate for betanin and soluble solids was observed between 3 and 6 weeks after sowing in both untreated and ethephon-treated beetroots. Overall, the expression of the betalain biosynthetic genes (CYP76AD1, CYP76AD5, CYP76AD6 and DODA1), determining the formation of both betanin and vulgaxanthin, increased in response to ethephon treatment, as did the expression of the betalain pathway activator BvMYB1. In the postharvest environment, the use of short-term UV-B radiation (1.23 kJ m- 2) followed by storages for 3 and 7 days at 15 °C resulted in increased betanin to vulgaxanthin ratio (51%) and phenolic content (15%).

CONCLUSIONS: The results of this study provide novel strategies to improve key profitability traits in betalain production. High betanin concentration and high betanin to vulgaxanthin ratio increase the commercial value of the colourant product. In addition, lowering soluble solids levels facilitates higher concentration of beetroot colour during processing. Moreover, we show that enhanced betanin content in ethephon-treated beetroots is linked to increased expression of betalain biosynthetic genes.}, } @article {pmid30509179, year = {2018}, author = {Anguraj Vadivel, AK and Krysiak, K and Tian, G and Dhaubhadel, S}, title = {Genome-wide identification and localization of chalcone synthase family in soybean (Glycine max [L]Merr).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {325}, pmid = {30509179}, issn = {1471-2229}, mesh = {Acyltransferases/*genetics ; Chromosome Mapping ; Chromosomes, Plant/genetics ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Genetic Loci/genetics ; Phylogeny ; Sequence Alignment ; Soybeans/enzymology/*genetics ; }, abstract = {BACKGROUND: Soybean is a paleopolyploid that has undergone two whole genome duplication events. Gene duplication is a type of genomic change that can lead to novel functions of pre-existing genes. Chalcone synthase (CHS) is the plant-specific type III polyketide synthase that catalyzes the first committed step in (iso)flavonoid biosynthesis in plants.

RESULTS: Here we performed a genome-wide search of CHS genes in soybean, and identified 21 GmCHS loci containing 14 unique GmCHS (GmCHS1-GmCHS14) that included 5 newly identified GmCHSs (GmCHS10-GmCHS14). Furthermore, 3 copies of GmCHS3 and 2 copies of GmCHS4 were found in soybean. Analysis of gene structure of GmCHSs revealed the presence of a single intron in protein-coding regions except for GmCHS12 that contained 3 introns. Even though GmCHS genes are located on 8 different chromosomes, a large number of these genes are present on chromosome 8 where they form 3 distinct clusters. Expression analysis of GmCHS genes revealed tissue-specific expression pattern, and that some GmCHS isoforms localize in the cytoplasm and the nucleus while other isoforms are restricted to cytoplasm only.

CONCLUSION: Overall, we have identified 21 GmCHS loci with 14 unique GmCHS genes in the soybean genome. Their gene structures and genomic organization together with the spatio-temporal expression and protein localization suggest their importance in the production of downstream metabolites such as (iso)flavonoids and their derived phytoalexins.}, } @article {pmid30509177, year = {2018}, author = {Jagot, S and Sabin, N and Le Cam, A and Bugeon, J and Rescan, PY and Gabillard, JC}, title = {Histological, transcriptomic and in vitro analysis reveal an intrinsic activated state of myogenic precursors in hyperplasic muscle of trout.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {865}, pmid = {30509177}, issn = {1471-2164}, abstract = {BACKGROUND: The dramatic increase in myotomal muscle mass in post-hatching fish is related to their ability to lastingly produce new muscle fibres, a process termed hyperplasia. The molecular and cellular mechanisms underlying fish muscle hyperplasia largely remain unknown. In this study, we aimed to characterize intrinsic properties of myogenic cells originating from hyperplasic fish muscle. For this purpose, we compared in situ proliferation, in vitro cell behavior and transcriptomic profile of myogenic precursors originating from hyperplasic muscle of juvenile trout (JT) and from non-hyperplasic muscle of fasted juvenile trout (FJT) and adult trout (AT).

RESULTS: For the first time, we showed that myogenic precursors proliferate in hyperplasic muscle from JT as shown by in vivo BrdU labeling. This proliferative rate was very low in AT and FJT muscle. Transcriptiomic analysis revealed that myogenic cells from FJT and AT displayed close expression profiles with only 64 differentially expressed genes (BH corrected p-val < 0.001). In contrast, 2623 differentially expressed genes were found between myogenic cells from JT and from both FJT and AT. Functional categories related to translation, mitochondrial activity, cell cycle, and myogenic differentiation were inferred from genes up regulated in JT compared to AT and FJT myogenic cells. Conversely, Notch signaling pathway, that signs cell quiescence, was inferred from genes down regulated in JT compared to FJT and AT. In line with our transcriptomic data, in vitro JT myogenic precursors displayed higher proliferation and differentiation capacities than FJT and AT myogenic precursors.

CONCLUSIONS: The transcriptomic analysis and examination of cell behavior converge to support the view that myogenic cells extracted from hyperplastic muscle of juvenile trout are intrinsically more potent to form myofibres than myogenic cells extracted from non-hyperplasic muscle. The generation of gene expression profiles in myogenic cell extracted from muscle of juvenile trout may yield insights into the molecular and cellular mechanisms controlling hyperplasia and provides a useful list of potential molecular markers of hyperplasia.}, } @article {pmid30509176, year = {2018}, author = {Jaiswar, A and Varshney, D and Adholeya, A and Prasad, P}, title = {Do environmentally induced DNA variations mediate adaptation in Aspergillus flavus exposed to chromium stress in tannery sludge?.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {868}, pmid = {30509176}, issn = {1471-2164}, abstract = {BACKGROUND: Environmental stress induced genetic polymorphisms have been suggested to arbitrate functional modifications influencing adaptations in microbes. The relationship between the genetic processes and concomitant functional adaptation can now be investigated at a genomic scale with the help of next generation sequencing (NGS) technologies. Using a NGS approach we identified genetic variations putatively underlying chromium tolerance in a strain of Aspergillus flavus isolated from a tannery sludge. Correlation of nsSNPs in the candidate genes (n = 493) were investigated for their influence on protein structure and possible function. Whole genome sequencing of chromium tolerant A. flavus strain (TERIBR1) was done (Illumina HiSeq2000). The alignment of quality trimmed data of TERIBR1 with reference NRRL3357 (accession number EQ963472) strain was performed using Bowtie2 version 2.2.8. SNP with a minimum read depth of 5 and not in vicinity (10 bp) of INDEL were filtered. Candidate genes conferring chromium resistance were selected and SNPs were identified. Protein structure modeling and interpretation for protein-ligand (CrO4- 2) docking for selected proteins harbouring non-synonymous substitutions were done using Phyre2 and PatchDock programs.

RESULTS: High rate of nsSNPs (approximately 11/kb) occurred in selected candidate genes for chromium tolerance. Of the 16 candidate genes selected for studying effect of nsSNPs on protein structure and protein-ligand interaction, four proteins belonging to the Major Facilitator Superfamily (MFS) and recG protein families showed significant interaction with chromium ion only in the chromium tolerant A. flavus strain TERIBR1.

CONCLUSIONS: Presence of nsSNPs and subsequent amino-acid alterations evidently influenced the 3D structures of the candidate proteins, which could have led to improved interaction with (CrO4- 2) ion. Such structural modifications might have enhanced chromium efflux efficiency of A. flavus (TERIBR1) and thereby offered the adaptation benefits in counteracting chromate stress. Our findings are of fundamental importance to the field of heavy-metal bio-remediation.}, } @article {pmid30509175, year = {2018}, author = {Oczkowicz, M and Szmatoła, T and Świątkiewicz, M and Pawlina-Tyszko, K and Gurgul, A and Ząbek, T}, title = {Corn dried distillers grains with solubles (cDDGS) in the diet of pigs change the expression of adipose genes that are potential therapeutic targets in metabolic and cardiovascular diseases.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {864}, pmid = {30509175}, issn = {1471-2164}, support = {This research was financed by the National Science Center Poland (grant no 2014/13/B/NZ9/02134)//National Science Center Poland/ ; }, abstract = {BACKGROUND: Corn dried distillers grains with solubles (cDDGS) are a byproduct of biofuel and alcohol production. cDDGS have been used in pig feed for many years, because they are readily available and rich in protein, fiber, unsaturated fatty acids and phytosterols. However, feed mixtures too high in cDDGS result in the worsening of backfat quality. We performed RNA-sequencing analysis of backfat from crossbred pigs fed different diets. The diets were isoenergetic but contained different amounts of cDDGS and various sources of fats. The animals were divided into four dietary groups during the two months of experimentation: group I (control (-cDDGS+rapeseed oil)), group II (+cDDGS+rapeseed oil), group III (+cDDGS+beef tallow), and group IV (+cDDGS+coconut oil). The aim of the present experiment was to evaluate changes in the backfat transcriptome of pigs fed isoenergetic diets that differed in cDDGS presence.

RESULTS: Via DESeq2 software, we identified 93 differentially expressed genes (DEGs) between groups I and II, 13 between groups I and III, and 125 between groups I and IV. DEGs identified between group I (-cDDGS+rapeseed oil) and group II (+cDDGS+rapeseed oil) were highly overrepresented in several KEGG pathways: metabolic pathways (FDR < 1.21e-06), oxidative phosphorylation (FDR < 0.00189), fatty acid biosynthesis (FDR < 0.00577), Huntington's disease (FDR < 0.00577), fatty acid metabolism (FDR < 0.0112), Parkinson's disease (FDR < 0.0151), non-alcoholic fatty liver disease (NAFLD) (FDR < 0.016), Alzheimer's disease (FDR < 0.0211) and complement and coagulation cascades (FDR < 0.02).

CONCLUSIONS: We observed that the addition of cDDGS positively affects the expression of several genes that have been recently proposed as potential targets for the treatment of obesity, diabetes, cardiovascular disease, and Alzheimer's disease (e.g., FASN, AACS, ALAS1, HMGCS1, and VSIG4). Thus, our results support the idea of including cDDGS into the diets of companion animals and humans and encourage research into the bioactive ingredients of cDDGS.}, } @article {pmid30509174, year = {2018}, author = {Abdulaal, WH}, title = {Purification and characterization of cysteine protease from miswak Salvadora persica.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {10}, pmid = {30509174}, issn = {1471-2091}, support = {438-130-204//King Abdulaziz University (SA)/ ; }, abstract = {BACKGROUND: Generally, proteases in medicinal plants had different therapeutic effects such as anti-inflammatory effect; modulate the immune response and inhibitory effect toward tumor growth. In this study, protease was purified and characterized from miswak roots, as medicinal plant and natural toothbrush.

RESULTS: Physical and chemical characterization of cysteine protease P1 were studied such as pH optimum (6.5), optimum temperature (50 °C), thermal stability (50 °C) and Km (3.3 mg azocasein/ml). The enzyme digested some proteins in the order of caseine > haemoglobin > egg albumin >gelatin > bovine serum albumin. Hg2+ had strong inhibitory effect on enzyme activity compared with other metal ions. Kinetic of inhibition for determination the type of protease was studied. Iodoactamide and p-Hydroximercuribenzaoic acid (p-HMB) caused strong inhibitory effect on enzyme activity indicating the enzyme is cysteine protease.

CONCLUSIONS: The biochemical characterization of this enzyme will be display the suitable conditions for using of this enzyme in toothpaste in the future and the enzyme may be used in other applications.}, } @article {pmid30509173, year = {2018}, author = {Sona, P and Hong, JH and Lee, S and Kim, BJ and Hong, WY and Jung, J and Kim, HN and Kim, HL and Christopher, D and Herviou, L and Im, YH and Lee, KY and Kim, TS and Jung, J}, title = {Integrated genome sizing (IGS) approach for the parallelization of whole genome analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {462}, pmid = {30509173}, issn = {1471-2105}, support = {A2014DD101//INNOPOLIS Foundation/ ; HI14C0072//Ministry of Health & Welfare, Korea/ ; }, mesh = {Genome Size/*genetics ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The use of whole genome sequence has increased recently with rapid progression of next-generation sequencing (NGS) technologies. However, storing raw sequence reads to perform large-scale genome analysis pose hardware challenges. Despite advancement in genome analytic platforms, efficient approaches remain relevant especially as applied to the human genome. In this study, an Integrated Genome Sizing (IGS) approach is adopted to speed up multiple whole genome analysis in high-performance computing (HPC) environment. The approach splits a genome (GRCh37) into 630 chunks (fragments) wherein multiple chunks can simultaneously be parallelized for sequence analyses across cohorts.

RESULTS: IGS was integrated on Maha-Fs (HPC) system, to provide the parallelization required to analyze 2504 whole genomes. Using a single reference pilot genome, NA12878, we compared the NGS process time between Maha-Fs (NFS SATA hard disk drive) and SGI-UV300 (solid state drive memory). It was observed that SGI-UV300 was faster, having 32.5 mins of process time, while that of the Maha-Fs was 55.2 mins.

CONCLUSIONS: The implementation of IGS can leverage the ability of HPC systems to analyze multiple genomes simultaneously. We believe this approach will accelerate research advancement in personalized genomic medicine. Our method is comparable to the fastest methods for sequence alignment.}, } @article {pmid30509172, year = {2018}, author = {Timms, VJ and Nguyen, T and Crighton, T and Yuen, M and Sintchenko, V}, title = {Genome-wide comparison of Corynebacterium diphtheriae isolates from Australia identifies differences in the Pan-genomes between respiratory and cutaneous strains.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {869}, pmid = {30509172}, issn = {1471-2164}, support = {Program Round 4//NSW Ministry of Health/ ; }, abstract = {BACKGROUND: Corynebacterium diphtheriae is the main etiological agent of diphtheria, a global disease causing life-threatening infections, particularly in infants and children. Vaccination with diphtheria toxoid protects against infection with potent toxin producing strains. However a growing number of apparently non-toxigenic but potentially invasive C. diphtheriae strains are identified in countries with low prevalence of diphtheria, raising key questions about genomic structures and population dynamics of the species. This study examined genomic diversity among 48 C. diphtheriae isolates collected in Australia over a 12-year period using whole genome sequencing. Phylogeny was determined using SNP-based mapping and genome wide analysis.

RESULTS: C. diphtheriae sequence type (ST) 32, a non-toxigenic clone with evidence of enhanced virulence that has been also circulating in Europe, appears to be endemic in Australia. Isolates from temporospatially related patients displayed the same ST and similarity in their core genomes. The genome-wide analysis highlighted a role of pilins, adhesion factors and iron utilization in infections caused by non-toxigenic strains.

CONCLUSIONS: The genomic diversity of toxigenic and non-toxigenic strains of C. diphtheriae in Australia suggests multiple sources of infection and colonisation. Genomic surveillance of co-circulating toxigenic and non-toxigenic C. diphtheriae offer new insights into the evolution and virulence of pathogenic clones and can inform targeted public health actions and policy. The genomes presented in this investigation will contribute to the global surveillance of C. diphtheriae both for the monitoring of antibiotic resistance genes and virulent strains such as those belonging to ST32.}, } @article {pmid30509171, year = {2018}, author = {Chen, S and Xia, J and Li, C and Zuo, L and Wei, X}, title = {The possible molecular mechanisms of farnesol on the antifungal resistance of C. albicans biofilms: the regulation of CYR1 and PDE2.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {203}, pmid = {30509171}, issn = {1471-2180}, support = {81271151//National Natural Sciences Foundation of China/ ; 81371156//National Natural Sciences Foundation of China/ ; PAPD,2014-37//Foundation of the Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {BACKGROUND: Farnesol has potential antifungal activity against Candida albicans biofilms, but the molecular mechanism of this activity is still unclear. Farnesol inhibits hyphal growth by regulating the cyclic AMP (cAMP) signalling pathway in C. albicans, and CYR1 and PDE2 regulate a pair of enzymes that are directly responsible for cAMP synthesis and degradation. Here, we hypothesize that farnesol enhances the antifungal susceptibility of C. albicans biofilms by regulating CYR1 and PDE2.

RESULTS: The resistance of the CYR1- and PDE2-overexpressing strains to caspofungin, itraconazole and terbinafine was increased in planktonic cells, and that to amphotericin B was increased in biofilms. Meanwhile, the biofilms of the CYR1- and PDE2-overexpressing strains were thicker (all p < 0.05) and consisted of more hyphae than that of the wild strain. The intracellular cAMP levels were higher in the biofilms of the CYR1-overexpressing strain than that in the biofilms of the wild strain (all p < 0.01), while no changes were found in the PDE2-overexpressing strain. Exogenous farnesol decreased the resistance of the CYR1- and PDE2-overexpressing strains to these four antifungals, repressed the hyphal and biofilm formation of the strains, and decreased the intracellular cAMP level in the biofilms (all p < 0.05) compared to the untreated controls. In addition, farnesol decreased the expression of the gene CYR1 and the protein CYR1 in biofilms of the CYR1-overexpressing strain (all p < 0.05) but increased the expression of the gene PDE2 and the protein PDE2 in biofilms of the PDE2-overexpressing strain (all p < 0.01).

CONCLUSIONS: The results indicate that CYR1 and PDE2 regulate the resistance of C. albicans biofilms to antifungals. Farnesol suppresses the resistance of C. albicans biofilms to antifungals by regulating the expression of the gene CYR1 and PDE2, while PDE2 regulation was subordinate to CYR1 regulation.}, } @article {pmid30509170, year = {2018}, author = {Owen, D and Bracher-Smith, M and Kendall, KM and Rees, E and Einon, M and Escott-Price, V and Owen, MJ and O'Donovan, MC and Kirov, G}, title = {Effects of pathogenic CNVs on physical traits in participants of the UK Biobank.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {867}, pmid = {30509170}, issn = {1471-2164}, support = {G0800509//Medical Research Council/United Kingdom ; MR/L010305/1//Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Copy number variants (CNVs) have been shown to increase risk for physical anomalies, developmental, psychiatric and medical disorders. Some of them have been associated with changes in weight, height, and other physical traits. As most studies have been performed on children and young people, these effects of CNVs in middle-aged and older people are not well established. The UK Biobank recruited half a million adults who provided a variety of physical measurements. We called all CNVs from the Affymetrix microarrays and selected a set of 54 CNVs implicated as pathogenic (including their reciprocal deletions/duplications) and that were found in five or more persons. Linear regression analysis was used to establish their association with 16 physical traits relevant to human health.

RESULTS: 396,725 participants of white British or Irish descent (excluding first-degree relatives) passed our quality control filters. Out of the 864 CNV/trait associations, 214 were significant at a false discovery rate of 0.1, most of them novel. Many of these traits increase risk for adverse health outcomes: e.g. increases in weight, waist-to-hip ratio, pulse rate and body fat composition. Deletions at 16p11.2, 16p12.1, NRXN1 and duplications at 16p13.11 and 22q11.2 produced the highest numbers of significant associations. Five CNVs produced average changes of over one standard deviation for the 16 traits, compared to controls: deletions at 16p11.2 and 22q11.2, and duplications at 3q29, the Williams-Beuren and Potocki-Lupski regions. CNVs at 1q21.1, 2q13, 16p11.2 and 16p11.2 distal, 16p12.1, 17p12 and 17q12 demonstrated one or more mirror image effects of deletions versus duplications.

CONCLUSIONS: Carriers of many CNVs should be monitored for physical traits that increase morbidity and mortality. Genes within these CNVs can give insights into biological processes and therapeutic interventions.}, } @article {pmid30509169, year = {2018}, author = {Fujiwara, K and Matsuura, K and Matsunami, K and Iio, E and Nojiri, S}, title = {Characterization of hepatitis B virus with complex structural variations.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {202}, pmid = {30509169}, issn = {1471-2180}, support = {25461004//Japan Society for the Promotion of Science/ ; }, abstract = {BACKGROUND: Hepatitis B virus (HBV) infection is one of the most serious public health issues. Recent HBV genetic research has revealed novel genetic rearrangements termed complex structural variations (SVs), which are composed of combinations of SVs such as insertions, deletions, and duplications. An extensive search was made for complex SVs of HBV and their characteristics were analyzed.

RESULTS: Fifty-five HBV strains with complex SVs were identified by analyzing genetic sequences of HBV with bioinformatical tools. Along with 15 HBV strains with complex SVs in a previous report, a total of 70 HBV strains harboring complex SVs were analyzed. Complex SVs in the HBV genome were located frequently between nt 1500 and 2000. Insertions were observed in 65/70 (92.9%) of HBV strains with complex SVs. As insertional motif sequences, hepatocyte nuclear factor 1 binding site, a sequence complementary to part of box α in enhancer II, and insertions of unknown origins were observed. The complex SVs were classified into six groups, and combination of insertion and deletion was observed more frequently than other patterns.

CONCLUSION: Through an extensive search of HBV sequences, new strains with complex SVs were identified in this study. Characteristics of HBV with complex SVs were clarified by the analysis of 70 HBV strains harboring complex SVs. Further investigation is required to elucidate its role in pathogenesis of HBV-related liver disease.}, } @article {pmid30509168, year = {2018}, author = {Suryavanshi, N and Furmston, J and Ridley, AJ}, title = {The STRIPAK complex components FAM40A and FAM40B regulate endothelial cell contractility via ROCKs.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {26}, doi = {10.1186/s12860-018-0175-y}, pmid = {30509168}, issn = {1471-2121}, support = {C6620/A15961//Cancer Research UK/United Kingdom ; }, abstract = {BACKGROUND: Endothelial cells provide a barrier between blood and tissues, which is regulated to allow molecules and cells in out of tissues. Patients with cerebral cavernous malformations (CCM) have dilated leaky blood vessels, especially in the central nervous system. A subset of these patients has loss-of-function mutations in CCM3. CCM3 is part of the STRIPAK protein complex that includes the little-characterized proteins FAM40A and FAM40B.

RESULTS: We show here that FAM40A and FAM40B can interact with CCM3. Knockdown of CCM3, FAM40A or FAM40B in endothelial cells by RNAi causes an increase in stress fibers and a reduction in loop formation in an in vitro angiogenesis assay, which can be reverted by inhibiting the Rho-regulated ROCK kinases. FAM40B depletion also increases endothelial permeability.

CONCLUSIONS: These results demonstrate the importance of the FAM40 proteins for endothelial cell physiology, and suggest that they act as part of the CCM3-containing STRIPAK complex.}, } @article {pmid30509167, year = {2018}, author = {Pereira, L and Ruggieri, V and Pérez, S and Alexiou, KG and Fernández, M and Jahrmann, T and Pujol, M and Garcia-Mas, J}, title = {QTL mapping of melon fruit quality traits using a high-density GBS-based genetic map.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {324}, pmid = {30509167}, issn = {1471-2229}, support = {AGL2015-64625-C2-1-R//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; }, mesh = {*Chromosome Mapping ; Cucurbitaceae/anatomy & histology/*genetics ; Food Quality ; Fruit/anatomy & histology/*genetics/standards ; Genetic Association Studies ; Genome, Plant/genetics ; Genotyping Techniques ; High-Throughput Nucleotide Sequencing ; Quantitative Trait Loci/*genetics ; }, abstract = {BACKGROUND: Melon shows a broad diversity in fruit morphology and quality, which is still underexploited in breeding programs. The knowledge of the genetic basis of fruit quality traits is important for identifying new alleles that may be introduced in elite material by highly efficient molecular breeding tools.

RESULTS: In order to identify QTLs controlling fruit quality, a recombinant inbred line population was developed using two commercial cultivars as parental lines: "Védrantais", from the cantalupensis group, and "Piel de Sapo", from the inodorus group. Both have desirable quality traits for the market, but their fruits differ in traits such as rind and flesh color, sugar content, ripening behavior, size and shape. We used a genotyping-by-sequencing strategy to construct a dense genetic map, which included around five thousand variants distributed in 824 bins. The RIL population was phenotyped for quality and morphology traits, and we mapped 33 stable QTLs involved in sugar and carotenoid content, fruit and seed morphology and major loci controlling external color of immature fruit and mottled rind. The median confidence interval of the QTLs was 942 kb, suggesting that the high density of the genetic map helped in increasing the mapping resolution. Some of these intervals contained less than a hundred annotated genes, and an integrative strategy combining gene expression and resequencing data enabled identification of candidate genes for some of these traits.

CONCLUSION: Several QTLs controlling fruit quality traits in melon were identified and delimited to narrow genomic intervals, using a RIL population and a GBS-based genetic map.}, } @article {pmid30509166, year = {2018}, author = {Du, YT and Zhao, MJ and Wang, CT and Gao, Y and Wang, YX and Liu, YW and Chen, M and Chen, J and Zhou, YB and Xu, ZS and Ma, YZ}, title = {Identification and characterization of GmMYB118 responses to drought and salt stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {320}, pmid = {30509166}, issn = {1471-2229}, support = {2018ZX0800909B//National Transgenic Key Project of the Ministry of Agriculture of China/ ; 1639630D//Introduction of Wheat Germplasm with Fusarium Crown Rot Resistance and Molecular Marker-Assisted Breeding/ ; }, mesh = {Agrobacterium/metabolism ; Arabidopsis/metabolism/physiology ; Dehydration ; Gene Expression Regulation, Plant ; Genes, Plant/genetics ; Phylogeny ; Plant Proteins/genetics/*metabolism/physiology ; Plant Roots/microbiology ; Plants, Genetically Modified ; Real-Time Polymerase Chain Reaction ; Salt Stress ; Soybeans/genetics/metabolism/physiology ; Transcription Factors/genetics/*metabolism/physiology ; }, abstract = {BACKGROUND: Abiotic stress severely influences plant growth and development. MYB transcription factors (TFs), which compose one of the largest TF families, play an important role in abiotic stress responses.

RESULT: We identified 139 soybean MYB-related genes; these genes were divided into six groups based on their conserved domain and were distributed among 20 chromosomes (Chrs). Quantitative real-time PCR (qRT-PCR) indicated that GmMYB118 highly responsive to drought, salt and high temperature stress; thus, this gene was selected for further analysis. Subcellular localization revealed that the GmMYB118 protein located in the nucleus. Ectopic expression (EX) of GmMYB118 increased tolerance to drought and salt stress and regulated the expression of several stress-associated genes in transgenic Arabidopsis plants. Similarly, GmMYB118-overexpressing (OE) soybean plants generated via Agrobacterium rhizogenes (A. rhizogenes)-mediated transformation of the hairy roots showed improved drought and salt tolerance. Furthermore, compared with the control (CK) plants, the clustered, regularly interspaced, short palindromic repeat (CRISPR)-transformed plants exhibited reduced drought and salt tolerance. The contents of proline and chlorophyll in the OE plants were significantly greater than those in the CK plants, whose contents were greater than those in the CRISPR plants under drought and salt stress conditions. In contrast, the reactive oxygen species (ROS) and malondialdehyde (MDA) contents were significantly lower in the OE plants than in the CK plants, whose contents were lower than those in the CRISPR plants under stress conditions.

CONCLUSIONS: These results indicated that GmMYB118 could improve tolerance to drought and salt stress by promoting expression of stress-associated genes and regulating osmotic and oxidizing substances to maintain cell homeostasis.}, } @article {pmid30509165, year = {2018}, author = {Luoma, LM and Berry, FB}, title = {Molecular analysis of NPAS3 functional domains and variants.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {14}, pmid = {30509165}, issn = {1471-2199}, support = {MOP114921//Canadian Institutes of Health Research/Canada ; }, abstract = {BACKGROUND: NPAS3 encodes a transcription factor which has been associated with multiple human psychiatric and neurodevelopmental disorders. In mice, deletion of Npas3 was found to cause alterations in neurodevelopment, as well as a marked reduction in neurogenesis in the adult mouse hippocampus. This neurogenic deficit, alongside the reduction in cortical interneuron number, likely contributes to the behavioral and cognitive alterations observed in Npas3 knockout mice. Although loss of Npas3 has been found to affect proliferation and apoptosis, the molecular function of NPAS3 is largely uncharacterized outside of predictions based on its high homology to bHLH-PAS transcription factors. Here we set out to characterize NPAS3 as a transcription factor, and to confirm whether NPAS3 acts as predicted for a Class 1 bHLH-PAS family member.

RESULTS: Through these studies we have experimentally demonstrated that NPAS3 behaves as a true transcription factor, capable of gene regulation through direct association with DNA. NPAS3 and ARNT are confirmed to directly interact in human cells through both bHLH and PAS dimerization domains. The C-terminus of NPAS3 was found to contain a functional transactivation domain. Further, the NPAS3::ARNT heterodimer was shown to directly regulate the expression of VGF and TXNIP through binding of their proximal promoters. Finally, we assessed the effects of three human variants of NPAS3 on gene regulatory function and do not observe significant deficits.

CONCLUSIONS: NPAS3 is a true transcription factor capable of regulating expression of target genes through their promoters by directly cooperating with ARNT. The tested human variants of NPAS3 require further characterization to identify their effects on NPAS3 expression and function in the individuals that carry them. These data enhance our understanding of the molecular function of NPAS3 and the mechanism by which it contributes to normal and abnormal neurodevelopment and neural function.}, } @article {pmid30509164, year = {2018}, author = {Liu, Y and Qi, B and Xie, J and Wu, X and Ling, Y and Cao, X and Kong, F and Xin, J and Jiang, X and Wu, Q and Wang, W and Li, Q and Zhang, S and Wu, F and Zhang, D and Wang, R and Zhang, X and Li, W}, title = {Filtered reproductive long non-coding RNAs by genome-wide analyses of goat ovary at different estrus periods.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {866}, pmid = {30509164}, issn = {1471-2164}, support = {[2015]49//scientific innovative team in colleges and universities of Anhui province/ ; 31501958//the National Natural Science Foundation of China/ ; 31372273//the National Natural Science Foundation of China/ ; 31501906//the National Natural Science Foundation of China/ ; 31772566//the National Natural Science Foundation of China/ ; XDHX2016001//Fuyang government - Fuyang normal university transverse cooperation research project/ ; KJ2017A334//Key Project of the Natural Science Research Program of Anhui Higher Education Institutions./ ; 1708085MC61//the Natural Science Fund Project in Anhui Province (grant number/ ; 2014//the Major Project of Biology Discipline Construction in Anhui Province/ ; KJ2017A339//Key Project of the Natural Science Research Program of Anhui Higher Education Institutions/ ; }, abstract = {BACKGROUND: The goat is an important farm animal. Reproduction is an important process of goat farming. The ovary is the most important reproductive organ for goats. In recent years, an increasing number of long non-coding RNAs (lncRNAs) have been implicated in the regulation of mammal reproduction. However, there are few studies on the function of lncRNAs in reproduction, particularly lncRNAs in the ovary.

RESULTS: The sequencing of goat ovaries generated 1,122,014,112 clean reads, and 4926 lncRNAs and 1454 TUCPs (transcripts of uncertain coding potential) were identified for further analysis by using the coding potential analysis software, CNCI, CPC and Pfam-sca. There were 115 /22 differential lncRNAs /TUCPs transcripts between the ovaries of the luteal phase and the follicular phase. We predicted the related genes of lncRNA /TUCP based on co-expression and co-localization methods. In total, 2584 /904 genes were predicted by co-expression, and 326/73 genes were predicted by co-localization. The functions of these genes were further analyzed with GO and KEGG analysis. The results showed that lncRNAs /TUCPs, which are highly expressed in goat ovaries in the luteal phase, are mainly associated with the synthesis of progesterone, and we filtered the lncRNAs /TUCPs, such as XR_001918177.1 and TUCP_001362, which may regulate the synthesis of progesterone; lncRNAs /TUCPs, which are highly expressed in goat ovaries in the follicular phase, are mainly associated with oogenesis and the maturation of oocytes, and we filtered the lncRNAs /TUCPs that may regulate the oogenesis and maturation of oocyte, such as XR_001917388.1 and TUCP_000849.

CONCLUSION: The present study provided the genome expression profile of lncRNAs /TUCPs in goat ovaries at different estrus periods and filtered the potential lncRNAs /TUCPs associated with goat reproduction. These results are helpful to further study the molecular mechanisms of goat reproduction.}, } @article {pmid30509163, year = {2018}, author = {Zhang, ZH and Zhou, T and Liao, Q and Yao, JY and Liang, GH and Song, HX and Guan, CY and Hua, YP}, title = {Integrated physiologic, genomic and transcriptomic strategies involving the adaptation of allotetraploid rapeseed to nitrogen limitation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {322}, pmid = {30509163}, issn = {1471-2229}, support = {2017YFD0200100 and 2017YFD0200103//National Key Research and Development Program of China/ ; 31101596 and 31372130//National Natural Science Foundation of China/ ; 31801923//National Natural Science Foundation of China/ ; }, mesh = {Adaptation, Physiological ; Anthocyanins/metabolism ; Brassica rapa/genetics/*metabolism/physiology ; Gene Expression Regulation, Plant ; Glutamate-Ammonia Ligase/metabolism ; Nitrates/metabolism ; Nitrogen/*deficiency/metabolism ; Tetraploidy ; }, abstract = {BACKGROUND: Nitrogen (N) is a macronutrient that is essential for optimal plant growth and seed yield. Allotetraploid rapeseed (AnAnCnCn, 2n = 4x = 38) has a higher requirement for N fertilizers whereas exhibiting a lower N use efficiency (NUE) than cereal crops. N limitation adaptation (NLA) is pivotal for enhancing crop NUE and reducing N fertilizer use in yield production. Therefore, revealing the genetic and molecular mechanisms underlying NLA is urgent for the genetic improvement of NUE in rapeseed and other crop species with complex genomes.

RESULTS: In this study, we integrated physiologic, genomic and transcriptomic analyses to comprehensively characterize the adaptive strategies of oilseed rape to N limitation stresses. Under N limitations, we detected accumulated anthocyanin, reduced nitrate (NO3-) and total N concentrations, and enhanced glutamine synthetase activity in the N-starved rapeseed plants. High-throughput transcriptomics revealed that the pathways associated with N metabolism and carbon fixation were highly over-represented. The expression of the genes that were involved in efficient N uptake, translocation, remobilization and assimilation was significantly altered. Genome-wide identification and molecular characterization of the microR827-NLA1-NRT1.7 regulatory circuit indicated the crucial role of the ubiquitin-mediated post-translational pathway in the regulation of rapeseed NLA. Transcriptional analysis of the module genes revealed their significant functional divergence in response to N limitations between allotetraploid rapeseed and the model Arabidopsis. Association analysis in a rapeseed panel comprising 102 genotypes revealed that BnaC5.NLA1 expression was closely correlated with the rapeseed low-N tolerance.

CONCLUSIONS: We identified the physiologic and genome-wide transcriptional responses of oilseed rape to N limitation stresses, and characterized the global members of the BnamiR827-BnaNLA1s-BnaNRT1.7s regulatory circuit. The transcriptomics-assisted gene co-expression network analysis accelerates the rapid identification of central members within large gene families of plant species with complex genomes. These findings would enhance our comprehensive understanding of the physiologic responses, genomic adaptation and transcriptomic alterations of oilseed rape to N limitations and provide central gene resources for the genetic improvement of crop NLA and NUE.}, } @article {pmid30509162, year = {2018}, author = {Zhang, Y and Hu, M and Liu, Q and Sun, L and Chen, X and Lv, L and Liu, Y and Jia, X and Li, H}, title = {Deletion of high-molecular-weight glutenin subunits in wheat significantly reduced dough strength and bread-baking quality.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {319}, pmid = {30509162}, issn = {1471-2229}, support = {HBCT2018010201//Modern Agricultural Industry Technology System - Hebei Province Wheat Innovation Team Construction/ ; 2017YF00100603//Cultivation of New Wheat Varieties with High Yield, High Quality and Water-Saving in North of Yellow and Huai Winter wheat Region/ ; 494-0402-YBN-RDC4//Modern Agricultural Science and Technology Innovation Project of Hebei Province/ ; 494-0402-JBN-C7GQ//Modern Agricultural Science and Technology Innovation Project of Hebei Province/ ; }, mesh = {*Bread/standards ; Cooking ; DNA Methylation ; Flour ; Glutens/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified ; RNA Interference ; Seeds/growth & development/metabolism ; Triticum/genetics/*metabolism ; }, abstract = {BACKGROUND: High-molecular-weight glutenin subunits (HMW-GS) play important roles in the elasticity of dough made from wheat. The HMW-GS null line is useful for studying the contribution of HMW-GS to the end-use quality of wheat.

METHODS: In a previous work, we cloned the Glu-1Ebx gene from Thinopyrum bessarabicum and introduced it into the wheat cultivar, Bobwhite. In addition to lines expressing the Glu-1Ebx gene, we also obtained a transgenic line (LH-11) with all the HMW-GS genes silenced. The HMW-GS deletion was stably inherited as a dominant and conformed to Mendel's laws. Expression levels of HMW-GS were determined by RT-PCR and epigenetic changes in methylation patterns and small RNAs were analyzed. Glutenins and gliadins were separated and quantitated by reversed-phase ultra-performance liquid chromatography. Measurement of glutenin macropolymer, and analysis of agronomic traits and end-use quality were also performed.

RESULTS: DNA methylation and the presence of small double-stranded RNA may be the causes of post-transcriptional gene silencing in LH-11. The accumulation rate and final content of glutenin macropolymer (GMP) in LH-11 were significantly lower than in wild-type (WT) Bobwhite. The total protein content was not significantly affected as the total gliadin content increased in LH-11 compared to WT. Deletion of HMW-GS also changed the content of different gliadin fractions. The ratio of ω-gliadin increased, whereas α/β- and γ-gliadins declined in LH-11. The wet gluten content, sedimentation value, development time and stability time of LH-11 were remarkably lower than that of Bobwhite. Bread cannot be made using the flour of LH-11.

CONCLUSIONS: Post-transcriptional gene silencing through epigenetic changes and RNA inhibition appear to be the causes for the gene expression deficiency in the transgenic line LH-11. The silencing of HMW-GW in LH-11 significantly reduced the dough properties, GMP content, wet gluten content, sedimentation value, development time and stability time of flour made from this wheat cultivar. The HMW-GS null line may provide a potential material for biscuit-making because of its low dough strength.}, } @article {pmid30509161, year = {2018}, author = {Zhang, L and Luo, H and Zhao, Y and Chen, X and Huang, Y and Yan, S and Li, S and Liu, M and Huang, W and Zhang, X and Jin, W}, title = {Maize male sterile 33 encodes a putative glycerol-3-phosphate acyltransferase that mediates anther cuticle formation and microspore development.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {318}, pmid = {30509161}, issn = {1471-2229}, support = {31801375//National Natural Science Foundation of China/ ; 91735305//National Natural Science Foundation of China/ ; 31471499//National Natural Science Foundation of China/ ; }, mesh = {Cloning, Molecular ; Flowers/*enzymology/growth & development/ultrastructure ; Glycerol-3-Phosphate O-Acyltransferase/genetics/*metabolism ; Lipids/biosynthesis ; Microscopy, Electron, Transmission ; Plant Infertility/*genetics ; Plant Proteins/genetics/*metabolism ; Pollen/*enzymology/growth & development ; Polyesters/metabolism ; Zea mays/*enzymology/genetics/growth & development ; }, abstract = {BACKGROUND: The anther cuticle, which is primarily composed of lipid polymers, is crucial for pollen development and plays important roles in sexual reproduction in higher plants. However, the mechanism underlying the biosynthesis of lipid polymers in maize (Zea mays. L.) remains unclear.

RESULTS: Here, we report that the maize male-sterile mutant shrinking anther 1 (sa1), which is allelic to the classic mutant male sterile 33 (ms33), displays defective anther cuticle development and premature microspore degradation. We isolated MS33 via map-based cloning. MS33 encodes a putative glycerol-3-phosphate acyltransferase and is preferentially expressed in tapetal cells during anther development. Gas chromatography-mass spectrometry revealed a substantial reduction in wax and cutin in ms33 anthers compared to wild type. Accordingly, RNA-sequencing analysis showed that many genes involved in wax and cutin biosynthesis are differentially expressed in ms33 compared to wild type.

CONCLUSIONS: Our findings suggest that MS33 may contribute to anther cuticle and microspore development by affecting lipid polyester biosynthesis in maize.}, } @article {pmid30509159, year = {2018}, author = {Gramlich, S and Wagner, ND and Hörandl, E}, title = {RAD-seq reveals genetic structure of the F2-generation of natural willow hybrids (Salix L.) and a great potential for interspecific introgression.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {317}, pmid = {30509159}, issn = {1471-2229}, support = {Ho 5462 7-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Hybridization of species with porous genomes can eventually lead to introgression via repeated backcrossing. The potential for introgression between species is reflected by the extent of segregation distortion in later generation hybrids. Here we studied a population of hybrids between Salix purpurea and S. helvetica that has emerged within the last 30 years on a glacier forefield in the European Alps due to secondary contact of the parental species. We used 5758 biallelic SNPs produced by RAD sequencing with the aim to ascertain the predominance of backcrosses (F1 hybrid x parent) or F2 hybrids (F1 hybrid x F1 hybrid) among hybrid offspring. Further, the SNPs were used to study segregation distortion in the second hybrid generation.

RESULTS: The analyses in STRUCTURE and NewHybrids revealed that the population consisted of parents and F1 hybrids, whereas hybrid offspring consisted mainly of backcrosses to either parental species, but also some F2 hybrids. Although there was a clear genetic differentiation between S. purpurea and S. helvetica (FST = 0.24), there was no significant segregation distortion in the backcrosses or the F2 hybrids. Plant height of the backcrosses resembled the respective parental species, whereas F2 hybrids were more similar to the subalpine S. helvetica.

CONCLUSIONS: The co-occurrence of the parental species and the hybrids on the glacier forefield, the high frequency of backcrossing, and the low resistance to gene flow via backcrossing make a scenario of introgression in this young hybrid population highly likely, potentially leading to the transfer of adaptive traits. We further suggest that this willow hybrid population may serve as a model for the evolutionary processes initiated by recent global warming.}, } @article {pmid30509158, year = {2018}, author = {Chen, L and Dong, R and Ma, Q and Zhang, Y and Xu, S and Ning, D and Chen, Q and Pei, D}, title = {Precocious genotypes and homozygous tendency generated by self-pollination in walnut.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {323}, pmid = {30509158}, issn = {1471-2229}, support = {31672126//National Natural Science Foundation of China/ ; }, mesh = {Genetic Association Studies ; Genotype ; *Homozygote ; Juglans/*genetics/physiology ; Microsatellite Repeats/genetics ; Pollination/*genetics/physiology ; Self-Incompatibility in Flowering Plants/genetics ; }, abstract = {BACKGROUND: Observations of precocious (early bearing) genotypes of walnut (Juglans regia L.) under natural conditions encouraged us to study the origin and genetic control of these fascinating traits.

RESULTS: In this study, the self-fertility, progeny performance, and simple sequence repeat (SSR) locus variation of iron walnut (Juglans sigillata Dode), an ecotype of J. regia, were investigated. The average self-pollinated fruit set rate of J. sigillata cv. 'Dapao' (DP) was 7.0% annually from 1979 to 1982. The average germination rate of self-pollinated seeds was 45.2% during the 4-year period. Most progeny had inbreeding depression. Nine representative self-pollinated progeny (SP1-SP9), with special or typical traits of DP, were selected. SP1-SP4 were precocious because they initiated flowers as early as 2 years after germination, compared to the 7-10-yr period that is typical of DP. SP9 had not flowered since 1980. Twelve SSR markers were used to analyze the SP and DP. The genome of SP had a tendency toward high levels of homozygosity. The high levels of homozygosity reported in 18 additional precocious walnut genotypes complemented the results of this study.

CONCLUSIONS: These results provide evidence of precocious phenotypes and genomes with high levels of homozygosity that might be generated from self-pollinating walnut. This suggests that self-pollination might facilitate the generation of unique homozygous parents for subsequent use in walnut-breeding programs. The results also indicate that more attention should be focused on adequate management of precocious walnut to avoid early depression in the production of nuts.}, } @article {pmid30500333, year = {2019}, author = {Ben Maamar, M and Nilsson, E and Sadler-Riggleman, I and Beck, D and McCarrey, JR and Skinner, MK}, title = {Developmental origins of transgenerational sperm DNA methylation epimutations following ancestral DDT exposure.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {280-293}, doi = {10.1016/j.ydbio.2018.11.016}, pmid = {30500333}, issn = {1095-564X}, support = {R01 ES012974/ES/NIEHS NIH HHS/United States ; }, abstract = {Epigenetic alterations in the germline can be triggered by a number of different environmental factors from diet to toxicants. These environmentally induced germline changes can promote the epigenetic transgenerational inheritance of disease and phenotypic variation. In previous studies, the pesticide DDT was shown to promote the transgenerational inheritance of sperm differential DNA methylation regions (DMRs), also called epimutations, which can in part mediate this epigenetic inheritance. In the current study, the developmental origins of the transgenerational DMRs during gametogenesis have been investigated. Male control and DDT lineage F3 generation rats were used to isolate embryonic day 16 (E16) prospermatogonia, postnatal day 10 (P10) spermatogonia, adult pachytene spermatocytes, round spermatids, caput epididymal spermatozoa, and caudal sperm. The DMRs between the control versus DDT lineage samples were determined at each developmental stage. The top 100 statistically significant DMRs at each stage were compared and the developmental origins of the caudal epididymal sperm DMRs were assessed. The chromosomal locations and genomic features of the different stage DMRs were analyzed. Although previous studies have demonstrated alterations in the DMRs of primordial germ cells (PGCs), the majority of the DMRs identified in the caudal sperm originated during the spermatogonia stages in the testis. Interestingly, a cascade of epigenetic alterations initiated in the PGCs is required to alter the epigenetic programming during spermatogenesis to obtain the sperm epigenetics involved in the epigenetic transgenerational inheritance phenomenon.}, } @article {pmid30499770, year = {2019}, author = {Sudha Rani, P and Saini, MK and Pinnaka, AK and Sampath Kumar, G and Kumar, S and Vemuluri, VR and Tanuku, NRS}, title = {Shewanella submarina sp. nov., a gammaproteobacterium isolated from marine water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {39-45}, doi = {10.1099/ijsem.0.003059}, pmid = {30499770}, issn = {1466-5034}, abstract = {A curved-rod-shaped bacterium was isolated from a marine (100 m depth) water sample collected from Bay of Bengal, Visakhapatnam, India. Strain NIO-S14T, was Gram-stain-negative, motile and pale-yellow. NIO-S14T was able to grow aerobically and anaerobically and could utilize a number of organic substrates. Major fatty acids were C12 : 0, iso-C13 : 0, C14 : 0, iso-C15 : 0, C16 : 0 and C16 : 1ω7c and/or C16 : 1ω6c (summed feature 3). NIO-S14T contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminophospholipids and six unidentified lipids as polar lipids. The DNA G+C content of NIO-S14T was 47.9 mol%. The 16S rRNA gene sequence comparisons indicated that the isolate represented a member of the family Shewanellaceae within the class Gammaproteobacteria. According to the results of 16S rRNA gene sequence analysis, NIO-S14T was closely related to Shewanella coralliiwith a pair-wise sequence similarity of 99.26 %. On the basis of the sequence comparison, NIO-S14T clustered with Shewanella coralliiand together they clustered with Shewanella mangroviand seven other species of the genus Shewanella but were distantly related. DNA-DNA hybridization between NIO-S14T and Shewanella corallii DSM 21332Trevealed a relatedness of 35 %. Distinct morphological, physiological and genotypic differences from these previously described taxa supported the classification of NIO-S14T as a representative of a novel species of the genus Shewanella, for which the name Shewanellasubmarina sp. nov. is proposed. The type strain of Shewanellasubmarina is NIO-S14T (=MTCC 12524T=KCTC 52277T=LMG 30752T).}, } @article {pmid30499769, year = {2019}, author = {Lee, SD}, title = {Martelella caricis sp. nov., isolated from a rhizosphere mudflat.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {266-270}, doi = {10.1099/ijsem.0.003149}, pmid = {30499769}, issn = {1466-5034}, abstract = {A novel marine bacterium, designated GH2-8T, was isolated from a rhizosphere mudflat of a halophyte (Carexscabrifolia) in Gangwha Island, Republic of Korea and its taxonomic status was investigated by a polyphasic approach. Cells of strain GH2-8T were Gram-stain-negative, strictly aerobic, oxidase-positive, catalase-positive and non-motile rods that showed growth at 10-30 °C, pH 5-10 and 0-11 % (w/v) NaCl. The predominant respiratory quinone was Q-10. The polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminolipid, an unidentified glycolipid and two unidentified lipids. The major fatty acids were summed feature 8, C16 : 0, C19 : 0cyclo ω8c, C18 : 1ω7c 11-methyl and summed feature 2. The G+C content of the genomic DNA was 53.4 mol%. Comparative analysis of the 16S rRNA gene sequences revealed that the organism belonged to the order 'Rhizobiales' and formed a distinct subline at the root of radiation encompassing members of the genus Martelella. The 16S rRNA gene sequence similarities to the phylogenetic neighbours were Martelella mediterranea (97.1 %), Martelella suaedae (96.9 %), Martelella endophytica (96.6 %), Martelella limonii (96.3 %), Martelella mangrovi (96.1 %) and Martelella radicis (95.5 %). Strain GH2-8T showed low 16S rRNA gene sequence similarities (<93.8 %) to other representatives of the order 'Rhizobiales'. On the basis of the results of phenotypic and phylogenetic analyses, strain GH2-8T (=KACC 19402T=KCCM 90275T=KCTC 62126T=NBRC 113213T) is considered to represent a novel species of the genus Martelella for which the name Martelellacaricis sp. nov. is proposed.}, } @article {pmid30499767, year = {2019}, author = {Chen, WM and Chen, WT and Young, CC and Sheu, SY}, title = {Flavobacterium niveum sp. nov., isolated from a freshwater creek.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {271-277}, doi = {10.1099/ijsem.0.003150}, pmid = {30499767}, issn = {1466-5034}, abstract = {Strain TAPW14T was isolated from a freshwater creek in Taiwan. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TAPW14T belonged to the genus Flavobacterium and was most closely related to Flavobacterium akiainvivens IK-1T (96.6 % sequence identity) and Flavobacterium hauense BX12T (96.0 %) and less than 96 % sequence similarity to other members of the genus. Cells of strain TAPW14T were Gram-negative, strictly aerobic, motile by gliding, rod-shaped and formed white colonies. Optimal growth occurred at 20 °C, pH 7 and in the presence of 0.5 % NaCl. Strain TAPW14T contained summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), iso-C15 : 0 and C16 : 0 as the predominant fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, three uncharacterized aminophospholipids, one uncharacterized phospholipid and one uncharacterized lipid. The major polyamine was homospermidine. The major isoprenoid quinone was MK-6. The DNA G+C content of the genomic DNA was 46.0 mol%. On the basis of the phylogenetic inference and phenotypic data, strain TAPW14T should be classified as a novel species, for which the name Flavobacteriumniveum sp. nov. is proposed. The type strain is TAPW14T (=BCRC 81055T=LMG 30057T=KCTC 52808T).}, } @article {pmid30499144, year = {2018}, author = {Karrenberg, S and Liu, X and Hallander, E and Favre, A and Herforth-Rahmé, J and Widmer, A}, title = {Ecological divergence plays an important role in strong but complex reproductive isolation in campions (Silene).}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13652}, pmid = {30499144}, issn = {1558-5646}, support = {2012-03622//Vetenskapsrådet/ ; 160123//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; FA1117/1-2//Deutsche Forschungsgemeinschaft/ ; }, abstract = {New species arise through the evolution of reproductive barriers between formerly interbreeding lineages. Yet, comprehensive assessments of potential reproductive barriers, which are needed to make inferences on processes driving speciation, are only available for a limited number of systems. In this study, we estimated individual and cumulative strengths of seven prezygotic and six postzygotic reproductive barriers between the recently diverged taxa Silene dioica (L.) Clairv. and S. latifolia Poiret using both published and new data. A combination of multiple partial reproductive barriers resulted in near-complete reproductive isolation between S. dioica and S. latifolia, consistent with earlier estimates of gene flow between the taxa. Extrinsic barriers associated with adaptive ecological divergence were most important, while intrinsic postzygotic barriers had moderate individual strength but contributed only little to total reproductive isolation. These findings are in line with ecological divergence as driver of speciation. We further found extensive variation in extrinsic reproductive isolation, ranging from sites with very strong selection against migrants and hybrids to intermediate sites where substantial hybridization is possible. This situation may allow for, or even promote, heterogeneous genetic divergence.}, } @article {pmid30499043, year = {2018}, author = {Bertocchi, NA and de Oliveira, TD and Del Valle Garnero, A and Coan, RLB and Gunski, RJ and Martins, C and Torres, FP}, title = {Distribution of CR1-like transposable element in woodpeckers (Aves Piciformes): Z sex chromosomes can act as a refuge for transposable elements.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {4}, pages = {333-343}, doi = {10.1007/s10577-018-9592-1}, pmid = {30499043}, issn = {1573-6849}, abstract = {Birds have relatively few repetitive sequences compared to other groups of vertebrates; however, the members of order Piciformes (woodpeckers) have more of these sequences, composed mainly of transposable elements (TE). The TE most often found in birds is a retrotransposon chicken repeat 1 (CR1). Piciformes lineages were subjected to an expansion of the CR1 elements, carrying a larger fraction of transposable elements. This study compared patterns of chromosome distribution among five bird species, through chromosome mapping of the CR1 sequence and reconstructed their phylogenetic tree. We analyzed several members of Piciformes (Colaptes campestris, Colaptes melanochloros, Melanerpes candidus, and Veniliornis spilogaster), as well as Galliformes (Gallus gallus). Gallus gallus is the species with which most genomic and hence cytogenetic studies have been performed. The results showed that CR1 sequences are a monophyletic group and do not depend on their hosts. All species analyzed showed a hybridization signal by fluorescence in situ hybridization (FISH). In all species, the chromosomal distribution of CR1 was not restricted to heterochromatin regions in the macrochromosomes, principally pair 1 and the Z sex chromosome. Accumulation in the Z sex chromosomes can serve as a refuge for transposable elements. These results highlight the importance of transposable elements in host genomes and karyotype evolution.}, } @article {pmid30498942, year = {2018}, author = {Anandan, K and Vittal, RR}, title = {Endophytic Paenibacillus amylolyticus KMCLE06 Extracted Dipicolinic Acid as Antibacterial Agent Derived via Dipicolinic Acid Synthetase Gene.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1605-y}, pmid = {30498942}, issn = {1432-0991}, abstract = {Bioactive natural compounds play pivotal roles in drug discovery and the emergence of multi-drug resistance pathogens demands the development of better/new drugs. Paenibacillus amylolyticus KMCLE06 endophytic bacterium isolated from the medicinal plant Coix lachryma-jobi were analyzed for the potential bioactive secondary metabolite compounds and its gene responsible within polyketide synthases (PKS) clusters. Ethyl acetate extraction of P. amylolyticus KMCLE06 showed significant antibacterial activity which was further processed to partial purification and characterization for bioactive compound. The foremost bioactive component in extraction was found to be dipicolinic acid (DPA). The antibacterial activity showed remarkable activity compared to the commercial standard DPA against both gram-positive and gram-negative pathogens. The MIC and MBC concentrations for partially purified extracted DPA ranged from 62.5 to 125 µg/ml and MBC from 208 to 250 µg/ml, respectively. Sequence analysis of gene amplified using degenerative primer, amplified 543 bp DNA region, revealing conserved putative open reading frame for dipicolinic acid synthetase (DpsA) key gene to produce DPA in most endospore forming bacteria. A search in the structural database for DpsA revealed significant homologous match with enoyl reductase one of the PKS type 1 module protein. This emphasizes endophytic P. amylolyticus KMCLE06 bacteria has presence of spoVF operon producing DPA via dipicolinic acid synthetase and lacks the polyketide synthase type 1 module cluster gene in its genome. And the bioactive compound DPA extracted acts as a stable remarkable antibacterial agent which can be potent compound for multi-resistance pathogens.}, } @article {pmid30498941, year = {2018}, author = {Gao, W and Zheng, C and Lei, Y and Kuang, W}, title = {Analysis of Bacterial Communities in White Clover Seeds via High-Throughput Sequencing of 16S rRNA Gene.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1607-9}, pmid = {30498941}, issn = {1432-0991}, support = {GJJ170294//Foundation of the Educational Department in Jiangxi Province/ ; 2014IK005//National Quality Supervision and Inspection Bureau of Science and Technology Planning Project/ ; }, abstract = {White clover widely cultivated in China is one of the most important perennial leguminous forages in temperate and subtropical regions. There is a large quantity of white clover seeds imported into China each year for demands of high-quality grass seeds. Seedborne diseases may cause significant economic losses. DNA sequencing technologies allow for the direct estimation of microbial community diversity, avoiding culture-based biases. Therefore, we used 16S rRNA gene sequencing to investigate the bacterial communities in white clover seeds collected from four different countries. The results showed that a total of 484,715 clean reads were obtained for further subsequent analysis. In total, 341, 340, 382, and 297 operational taxonomic units were obtained at 3% distance cutoff in DB, MB, TB, and XB samples, respectively. The richness indexes revealed that TB sample from Argentina had the highest bacterial richness in four samples. Our results demonstrated that Proteobacteria was the dominant phyla in MB, TB, and XB; however, Bacteroidetes was the dominant phyla in DB. The dominant genus of DB was Prevotella (11.9%), while Sphingomonas was the major genus of MB (46.9%), TB (55.08%), and XB (47.2%) samples. These results provide useful information for seedborne diseases and transmission of bacteria from seed to seedling.}, } @article {pmid30498561, year = {2018}, author = {Sakoula, D and Nowka, B and Spieck, E and Daims, H and Lücker, S}, title = {The draft genome sequence of "Nitrospira lenta" strain BS10, a nitrite oxidizing bacterium isolated from activated sludge.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {32}, pmid = {30498561}, issn = {1944-3277}, support = {339880//European Research Council/International ; }, abstract = {The genus Nitrospira is considered to be the most widespread and abundant group of nitrite-oxidizing bacteria in many natural and man-made ecosystems. However, the ecophysiological versatility within this phylogenetic group remains highly understudied, mainly due to the lack of pure cultures and genomic data. To further expand our understanding of this biotechnologically important genus, we analyzed the high quality draft genome of "Nitrospira lenta" strain BS10, a sublineage II Nitrospira that was isolated from a municipal wastewater treatment plant in Hamburg, Germany. The genome of "N. lenta" has a size of 3,756,190 bp and contains 3968 genomic objects, of which 3907 are predicted protein-coding sequences. Thorough genome annotation allowed the reconstruction of the "N. lenta" core metabolism for energy conservation and carbon fixation. Comparative analyses indicated that most metabolic features are shared with N. moscoviensis and "N. defluvii", despite their ecological niche differentiation and phylogenetic distance. In conclusion, the genome of "N. lenta" provides important insights into the genomic diversity of the genus Nitrospira and provides a foundation for future comparative genomic studies that will generate a better understanding of the nitrification process.}, } @article {pmid30498234, year = {2018}, author = {Robinson, JPW and Wilson, SK and Robinson, J and Gerry, C and Lucas, J and Assan, C and Govinden, R and Jennings, S and Graham, NAJ}, title = {Publisher Correction: Productive instability of coral reef fisheries after climate-driven regime shifts.}, journal = {Nature ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41559-018-0755-4}, pmid = {30498234}, issn = {2397-334X}, abstract = {In the version of this Article originally published, a technical error meant two proof corrections were not actioned. In the sentence that started "Fishery changes were underpinned…", a citation to ref. 9 was missing, and that to ref. 22 was misplaced. The sentence should have read: "Fishery changes were underpinned by species' differential responses to the post-bleaching benthic trajectories, suggesting that projections for reef fisheries that are based on habitat-driven loss of fish biomass (for example ref. 9) have overlooked the potential for increased productivity of low trophic levels22, particularly browsing herbivores on regime-shifted reefs." These errors have now been corrected in the Article.}, } @article {pmid30498167, year = {2019}, author = {Kjær, KS and Kaul, N and Prakash, O and Chábera, P and Rosemann, NW and Honarfar, A and Gordivska, O and Fredin, LA and Bergquist, KE and Häggström, L and Ericsson, T and Lindh, L and Yartsev, A and Styring, S and Huang, P and Uhlig, J and Bendix, J and Strand, D and Sundström, V and Persson, P and Lomoth, R and Wärnmark, K}, title = {Luminescence and reactivity of a charge-transfer excited iron complex with nanosecond lifetime.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6424}, pages = {249-253}, doi = {10.1126/science.aau7160}, pmid = {30498167}, issn = {1095-9203}, abstract = {Iron's abundance and rich coordination chemistry are potentially appealing features for photochemical applications. However, the photoexcitable charge-transfer states of most iron complexes are limited by picosecond or subpicosecond deactivation through low-lying metal-centered states, resulting in inefficient electron-transfer reactivity and complete lack of photoluminescence. In this study, we show that octahedral coordination of iron(III) by two mono-anionic facial tris-carbene ligands can markedly suppress such deactivation. The resulting complex [Fe(phtmeimb)2]+, where phtmeimb is {phenyl[tris(3-methylimidazol-1-ylidene)]borate}-, exhibits strong, visible, room temperature photoluminescence with a 2.0-nanosecond lifetime and 2% quantum yield via spin-allowed transition from a doublet ligand-to-metal charge-transfer (2LMCT) state to the doublet ground state. Reductive and oxidative electron-transfer reactions were observed for the 2LMCT state of [Fe(phtmeimb)2]+ in bimolecular quenching studies with methylviologen and diphenylamine.}, } @article {pmid30498166, year = {2018}, author = {Sahnouni, M and Parés, JM and Duval, M and Cáceres, I and Harichane, Z and van der Made, J and Pérez-González, A and Abdessadok, S and Kandi, N and Derradji, A and Medig, M and Boulaghraif, K and Semaw, S}, title = {1.9-million- and 2.4-million-year-old artifacts and stone tool-cutmarked bones from Ain Boucherit, Algeria.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1297-1301}, doi = {10.1126/science.aau0008}, pmid = {30498166}, issn = {1095-9203}, mesh = {Algeria ; Animals ; Bone and Bones ; Culturally Appropriate Technology/*history ; *Fossils ; History, Ancient ; *Hominidae ; *Tool Use Behavior ; }, abstract = {East Africa has provided the earliest known evidence for Oldowan stone artifacts and hominin-induced stone tool cutmarks dated to ~2.6 million years (Ma) ago. The ~1.8-million-year-old stone artifacts from Ain Hanech (Algeria) were considered to represent the oldest archaeological materials in North Africa. Here we report older stone artifacts and cutmarked bones excavated from two nearby deposits at Ain Boucherit estimated to ~1.9 Ma ago, and the older to ~2.4 Ma ago. Hence, the Ain Boucherit evidence shows that ancestral hominins inhabited the Mediterranean fringe in northern Africa much earlier than previously thought. The evidence strongly argues for early dispersal of stone tool manufacture and use from East Africa or a possible multiple-origin scenario of stone technology in both East and North Africa.}, } @article {pmid30498165, year = {2019}, author = {Steiner, S and Wolf, J and Glatzel, S and Andreou, A and Granda, JM and Keenan, G and Hinkley, T and Aragon-Camarasa, G and Kitson, PJ and Angelone, D and Cronin, L}, title = {Organic synthesis in a modular robotic system driven by a chemical programming language.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6423}, pages = {}, doi = {10.1126/science.aav2211}, pmid = {30498165}, issn = {1095-9203}, abstract = {The synthesis of complex organic compounds is largely a manual process that is often incompletely documented. To address these shortcomings, we developed an abstraction that maps commonly reported methodological instructions into discrete steps amenable to automation. These unit operations were implemented in a modular robotic platform by using a chemical programming language that formalizes and controls the assembly of the molecules. We validated the concept by directing the automated system to synthesize three pharmaceutical compounds, diphenhydramine hydrochloride, rufinamide, and sildenafil, without any human intervention. Yields and purities of products and intermediates were comparable to or better than those achieved manually. The syntheses are captured as digital code that can be published, versioned, and transferred flexibly between platforms with no modification, thereby greatly enhancing reproducibility and reliable access to complex molecules.}, } @article {pmid30498129, year = {2018}, author = {Aguisanda, F}, title = {At the end of the road, a new start.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1078}, doi = {10.1126/science.362.6418.1078}, pmid = {30498129}, issn = {1095-9203}, } @article {pmid30498128, year = {2018}, author = {Bian, S and Hou, Y and Zhou, X and Li, X and Yong, J and Wang, Y and Wang, W and Yan, J and Hu, B and Guo, H and Wang, J and Gao, S and Mao, Y and Dong, J and Zhu, P and Xiu, D and Yan, L and Wen, L and Qiao, J and Tang, F and Fu, W}, title = {Single-cell multiomics sequencing and analyses of human colorectal cancer.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1060-1063}, doi = {10.1126/science.aao3791}, pmid = {30498128}, issn = {1095-9203}, abstract = {Although genomic instability, epigenetic abnormality, and gene expression dysregulation are hallmarks of colorectal cancer, these features have not been simultaneously analyzed at single-cell resolution. Using optimized single-cell multiomics sequencing together with multiregional sampling of the primary tumor and lymphatic and distant metastases, we developed insights beyond intratumoral heterogeneity. Genome-wide DNA methylation levels were relatively consistent within a single genetic sublineage. The genome-wide DNA demethylation patterns of cancer cells were consistent in all 10 patients whose DNA we sequenced. The cancer cells' DNA demethylation degrees clearly correlated with the densities of the heterochromatin-associated histone modification H3K9me3 of normal tissue and those of repetitive element long interspersed nuclear element 1. Our work demonstrates the feasibility of reconstructing genetic lineages and tracing their epigenomic and transcriptomic dynamics with single-cell multiomics sequencing.}, } @article {pmid30498127, year = {2018}, author = {Chen, Z and Corlett, RT and Jiao, X and Liu, SJ and Charles-Dominique, T and Zhang, S and Li, H and Lai, R and Long, C and Quan, RC}, title = {Prolonged milk provisioning in a jumping spider.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1052-1055}, doi = {10.1126/science.aat3692}, pmid = {30498127}, issn = {1095-9203}, abstract = {Lactation is a mammalian attribute, and the few known nonmammal examples have distinctly different modalities. We document here milk provisioning in a jumping spider, which compares functionally and behaviorally to lactation in mammals. The spiderlings ingest nutritious milk droplets secreted from the mother's epigastric furrow until the subadult stage. Milk is indispensable for offspring survival in the early stages and complements their foraging in later stages. Maternal care, as for some long-lived vertebrates, continues after the offspring reach maturity. Furthermore, a female-biased adult sex ratio is acquired only when the mother is present. These findings demonstrate that mammal-like milk provisioning and parental care for sexually mature offspring have also evolved in invertebrates, encouraging a reevaluation of their occurrence across the animal kingdom, especially in invertebrates.}, } @article {pmid30498126, year = {2018}, author = {Zhang, XL and Ha, BB and Wang, SJ and Chen, ZJ and Ge, JY and Long, H and He, W and Da, W and Nian, XM and Yi, MJ and Zhou, XY and Zhang, PQ and Jin, YS and Bar-Yosef, O and Olsen, JW and Gao, X}, title = {The earliest human occupation of the high-altitude Tibetan Plateau 40 thousand to 30 thousand years ago.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1049-1051}, doi = {10.1126/science.aat8824}, pmid = {30498126}, issn = {1095-9203}, abstract = {The Tibetan Plateau is the highest and one of the most demanding environments ever inhabited by humans. We investigated the timing and mechanisms of its initial colonization at the Nwya Devu site, located nearly 4600 meters above sea level. This site, dating from 40,000 to 30,000 years ago, is the highest Paleolithic archaeological site yet identified globally. Nwya Devu has yielded an abundant blade tool assemblage, indicating hitherto-unknown capacities for the survival of modern humans who camped in this environment. This site deepens the history of the peopling of the "roof of the world" and the antiquity of human high-altitude occupations more generally.}, } @article {pmid30498125, year = {2018}, author = {Brodt, S and Gais, S and Beck, J and Erb, M and Scheffler, K and Schönauer, M}, title = {Fast track to the neocortex: A memory engram in the posterior parietal cortex.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1045-1048}, doi = {10.1126/science.aau2528}, pmid = {30498125}, issn = {1095-9203}, abstract = {Models of systems memory consolidation postulate a fast-learning hippocampal store and a slowly developing, stable neocortical store. Accordingly, early neocortical contributions to memory are deemed to reflect a hippocampus-driven online reinstatement of encoding activity. In contrast, we found that learning rapidly engenders an enduring memory engram in the human posterior parietal cortex. We assessed microstructural plasticity via diffusion-weighted magnetic resonance imaging as well as functional brain activity in an object-location learning task. We detected neocortical plasticity as early as 1 hour after learning and found that it was learning specific, enabled correct recall, and overlapped with memory-related functional activity. These microstructural changes persisted over 12 hours. Our results suggest that new traces can be rapidly encoded into the parietal cortex, challenging views of a slow-learning neocortex.}, } @article {pmid30498124, year = {2018}, author = {Kim, HH and Souliou, SM and Barber, ME and Lefrançois, E and Minola, M and Tortora, M and Heid, R and Nandi, N and Borzi, RA and Garbarino, G and Bosak, A and Porras, J and Loew, T and König, M and Moll, PJW and Mackenzie, AP and Keimer, B and Hicks, CW and Le Tacon, M}, title = {Uniaxial pressure control of competing orders in a high-temperature superconductor.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1040-1044}, doi = {10.1126/science.aat4708}, pmid = {30498124}, issn = {1095-9203}, abstract = {Cuprates exhibit antiferromagnetic, charge density wave (CDW), and high-temperature superconducting ground states that can be tuned by means of doping and external magnetic fields. However, disorder generated by these tuning methods complicates the interpretation of such experiments. Here, we report a high-resolution inelastic x-ray scattering study of the high-temperature superconductor YBa2Cu3O6.67 under uniaxial stress, and we show that a three-dimensional long-range-ordered CDW state can be induced through pressure along the a axis, in the absence of magnetic fields. A pronounced softening of an optical phonon mode is associated with the CDW transition. The amplitude of the CDW is suppressed below the superconducting transition temperature, indicating competition with superconductivity. The results provide insights into the normal-state properties of cuprates and illustrate the potential of uniaxial-pressure control of competing orders in quantum materials.}, } @article {pmid30498123, year = {2018}, author = {Lee, D and Chung, B and Shi, Y and Kim, GY and Campbell, N and Xue, F and Song, K and Choi, SY and Podkaminer, JP and Kim, TH and Ryan, PJ and Kim, JW and Paudel, TR and Kang, JH and Spinuzzi, JW and Tenne, DA and Tsymbal, EY and Rzchowski, MS and Chen, LQ and Lee, J and Eom, CB}, title = {Isostructural metal-insulator transition in VO2.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1037-1040}, doi = {10.1126/science.aam9189}, pmid = {30498123}, issn = {1095-9203}, abstract = {The metal-insulator transition in correlated materials is usually coupled to a symmetry-lowering structural phase transition. This coupling not only complicates the understanding of the basic mechanism of this phenomenon but also limits the speed and endurance of prospective electronic devices. We demonstrate an isostructural, purely electronically driven metal-insulator transition in epitaxial heterostructures of an archetypal correlated material, vanadium dioxide. A combination of thin-film synthesis, structural and electrical characterizations, and theoretical modeling reveals that an interface interaction suppresses the electronic correlations without changing the crystal structure in this otherwise correlated insulator. This interaction stabilizes a nonequilibrium metallic phase and leads to an isostructural metal-insulator transition. This discovery will provide insights into phase transitions of correlated materials and may aid the design of device functionalities.}, } @article {pmid30498122, year = {2018}, author = {, }, title = {A gamma-ray determination of the Universe's star formation history.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1031-1034}, doi = {10.1126/science.aat8123}, pmid = {30498122}, issn = {1095-9203}, abstract = {The light emitted by all galaxies over the history of the Universe produces the extragalactic background light (EBL) at ultraviolet, optical, and infrared wavelengths. The EBL is a source of opacity for gamma rays via photon-photon interactions, leaving an imprint in the spectra of distant gamma-ray sources. We measured this attenuation using 739 active galaxies and one gamma-ray burst detected by the Fermi Large Area Telescope. This allowed us to reconstruct the evolution of the EBL and determine the star formation history of the Universe over 90% of cosmic time. Our star formation history is consistent with independent measurements from galaxy surveys, peaking at redshift z ~ 2. Upper limits of the EBL at the epoch of reionization suggest a turnover in the abundance of faint galaxies at z ~ 6.}, } @article {pmid30498121, year = {2018}, author = {Danchin, E and Nöbel, S and Pocheville, A and Dagaeff, AC and Demay, L and Alphand, M and Ranty-Roby, S and van Renssen, L and Monier, M and Gazagne, E and Allain, M and Isabel, G}, title = {Cultural flies: Conformist social learning in fruitflies predicts long-lasting mate-choice traditions.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1025-1030}, doi = {10.1126/science.aat1590}, pmid = {30498121}, issn = {1095-9203}, abstract = {Despite theoretical justification for the evolution of animal culture, empirical evidence for it beyond mammals and birds remains scant, and we still know little about the process of cultural inheritance. In this study, we propose a mechanism-driven definition of animal culture and test it in the fruitfly. We found that fruitflies have five cognitive capacities that enable them to transmit mating preferences culturally across generations, potentially fostering persistent traditions (the main marker of culture) in mating preference. A transmission chain experiment validates a model of the emergence of local traditions, indicating that such social transmission may lead initially neutral traits to become adaptive, hence strongly selecting for copying and conformity. Although this situation was suggested decades ago, it previously had little empirical support.}, } @article {pmid30498120, year = {2018}, author = {Sommaruga, R and Rodríguez-Graña, L and Calliari, D and Lercari, D and Aubriot, L}, title = {Legislation restricts research in Uruguay.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1008}, doi = {10.1126/science.aav6122}, pmid = {30498120}, issn = {1095-9203}, } @article {pmid30498119, year = {2018}, author = {Simon, S and Otto, M and Engelhard, M}, title = {Scan the horizon for unprecedented risks.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1007-1008}, doi = {10.1126/science.aav7568}, pmid = {30498119}, issn = {1095-9203}, mesh = {*Agriculture ; *Conservation of Natural Resources ; Research ; Risk ; }, } @article {pmid30498118, year = {2018}, author = {Leshchinsky, BA and Booth, AM and Glover-Cutter, KM and Mohney, C and Olsen, MJ and Roering, JJ}, title = {Prepare for Cascadia's next earthquake.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1007}, doi = {10.1126/science.aav5615}, pmid = {30498118}, issn = {1095-9203}, } @article {pmid30498117, year = {2018}, author = {van Raalte, AA and Sasson, I and Martikainen, P}, title = {The case for monitoring life-span inequality.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1002-1004}, doi = {10.1126/science.aau5811}, pmid = {30498117}, issn = {1095-9203}, support = {//European Research Council/International ; }, } @article {pmid30498116, year = {2018}, author = {Kolb, R}, title = {Leon Max Lederman (1922-2018).}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1001}, doi = {10.1126/science.aav9603}, pmid = {30498116}, issn = {1095-9203}, } @article {pmid30498115, year = {2018}, author = {Goetz, JG}, title = {Metastases go with the flow.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {999-1000}, doi = {10.1126/science.aat9100}, pmid = {30498115}, issn = {1095-9203}, } @article {pmid30498114, year = {2018}, author = {Whiten, A}, title = {Culture and conformity shape fruitfly mating.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {998-999}, doi = {10.1126/science.aav5674}, pmid = {30498114}, issn = {1095-9203}, mesh = {Animals ; *Drosophila ; Marriage ; Reproduction ; Social Behavior ; Social Conformity ; *Social Learning ; }, } @article {pmid30498113, year = {2018}, author = {Rollett, A}, title = {One crystal out of many.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {996-997}, doi = {10.1126/science.aav6733}, pmid = {30498113}, issn = {1095-9203}, mesh = {Crystallization ; *Edible Grain ; *Metals ; }, } @article {pmid30498112, year = {2018}, author = {Prandini, E}, title = {Clues from gamma rays on the history of star birth.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {995-996}, doi = {10.1126/science.aav7344}, pmid = {30498112}, issn = {1095-9203}, mesh = {*Gamma Rays ; }, } @article {pmid30498111, year = {2018}, author = {Assaf, Y}, title = {New dimensions for brain mapping.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {994-995}, doi = {10.1126/science.aav7357}, pmid = {30498111}, issn = {1095-9203}, mesh = {Brain ; *Brain Mapping ; Magnetic Resonance Imaging ; Memory ; *Neocortex ; Parietal Lobe ; }, } @article {pmid30498110, year = {2018}, author = {Zhang, JF and Dennell, R}, title = {The last of Asia conquered by Homo sapiens.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {992-993}, doi = {10.1126/science.aav6863}, pmid = {30498110}, issn = {1095-9203}, mesh = {*Altitude ; Asia ; Biological Evolution ; Fossils ; Hominidae ; Humans ; *Occupations ; Tibet ; }, } @article {pmid30498109, year = {2018}, author = {Pennisi, E}, title = {Buying time.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {988-991}, doi = {10.1126/science.362.6418.988}, pmid = {30498109}, issn = {1095-9203}, } @article {pmid30498108, year = {2018}, author = {Cohen, J}, title = {Forgotten no more.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {984-987}, doi = {10.1126/science.362.6418.984}, pmid = {30498108}, issn = {1095-9203}, } @article {pmid30498107, year = {2018}, author = {Rabesandratana, T}, title = {European funders detail their open-access plan.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {983}, doi = {10.1126/science.362.6418.983}, pmid = {30498107}, issn = {1095-9203}, } @article {pmid30498106, year = {2018}, author = {Normile, D}, title = {China sets out for the far side of the moon.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {982-983}, doi = {10.1126/science.362.6418.982}, pmid = {30498106}, issn = {1095-9203}, } @article {pmid30498105, year = {2018}, author = {Lawler, A}, title = {Migrants and trade spiced up Canaanite metropolis.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {980-981}, doi = {10.1126/science.362.6418.980}, pmid = {30498105}, issn = {1095-9203}, } @article {pmid30498104, year = {2018}, author = {Voosen, P}, title = {Safely settled, InSight gets ready to look inside Mars.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {979-980}, doi = {10.1126/science.362.6418.979}, pmid = {30498104}, issn = {1095-9203}, } @article {pmid30498103, year = {2018}, author = {Normile, D}, title = {Shock greets claim of CRISPR-edited babies.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {978-979}, doi = {10.1126/science.362.6418.978}, pmid = {30498103}, issn = {1095-9203}, } @article {pmid30498102, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {976-977}, doi = {10.1126/science.362.6418.976}, pmid = {30498102}, issn = {1095-9203}, } @article {pmid30498101, year = {2018}, author = {Wyndham, JM and Vitullo, MW}, title = {Define the human right to science.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {975}, doi = {10.1126/science.aaw1467}, pmid = {30498101}, issn = {1095-9203}, } @article {pmid30498100, year = {2018}, author = {Litvak, Y and Byndloss, MX and Bäumler, AJ}, title = {Colonocyte metabolism shapes the gut microbiota.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {}, doi = {10.1126/science.aat9076}, pmid = {30498100}, issn = {1095-9203}, support = {R56 AI112949/AI/NIAID NIH HHS/United States ; R01 AI044170/AI/NIAID NIH HHS/United States ; R01 AI096528/AI/NIAID NIH HHS/United States ; R01 AI112949/AI/NIAID NIH HHS/United States ; R01 AI112445/AI/NIAID NIH HHS/United States ; }, abstract = {An imbalance in the colonic microbiota might underlie many human diseases, but the mechanisms that maintain homeostasis remain elusive. Recent insights suggest that colonocyte metabolism functions as a control switch, mediating a shift between homeostatic and dysbiotic communities. During homeostasis, colonocyte metabolism is directed toward oxidative phosphorylation, resulting in high epithelial oxygen consumption. The consequent epithelial hypoxia helps to maintain a microbial community dominated by obligate anaerobic bacteria, which provide benefit by converting fiber into fermentation products absorbed by the host. Conditions that alter the metabolism of the colonic epithelium increase epithelial oxygenation, thereby driving an expansion of facultative anaerobic bacteria, a hallmark of dysbiosis in the colon. Enteric pathogens subvert colonocyte metabolism to escape niche protection conferred by the gut microbiota. The reverse strategy, a metabolic reprogramming to restore colonocyte hypoxia, represents a promising new therapeutic approach for rebalancing the colonic microbiota in a broad spectrum of human diseases.}, } @article {pmid30498099, year = {2018}, author = {Chevallier, F}, title = {Comment on "Contrasting carbon cycle responses of the tropical continents to the 2015-2016 El Niño".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {}, doi = {10.1126/science.aar5432}, pmid = {30498099}, issn = {1095-9203}, abstract = {Liu et al (Research Articles, 13 October 2017) inferred carbon flux anomalies in tropical continents with enough confidence to constrain the driving carbon-exchange processes. I show that they underestimated their error budget and that more effort must be invested in the satellite concentration retrievals and in the atmospheric transport models before such precision can be achieved.}, } @article {pmid30498098, year = {2018}, author = {Liu, J and Bowman, KW and Schimel, D and Parazoo, NC and Jiang, Z and Lee, M and Bloom, AA and Wunch, D and Frankenberg, C and Sun, Y and O'Dell, CW and Gurney, KR and Menemenlis, D and Gierach, M and Crisp, D and Eldering, A}, title = {Response to Comment on "Contrasting carbon cycle responses of the tropical continents to the 2015-2016 El Niño".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {}, doi = {10.1126/science.aat1211}, pmid = {30498098}, issn = {1095-9203}, abstract = {Chevallier showed a column CO2 ([Formula: see text]) anomaly of ±0.5 parts per million forced by a uniform net biosphere exchange (NBE) anomaly of 2.5 gigatonnes of carbon over the tropical continents within a year, so he claimed that the inferred NBE uncertainties should be larger than presented in Liu et al We show that a much concentrated NBE anomaly led to much larger [Formula: see text] perturbations.}, } @article {pmid30498034, year = {2018}, author = {Terao, C and Yoshifuji, H and Matsumura, T and Naruse, TK and Ishii, T and Nakaoka, Y and Kirino, Y and Matsuo, K and Origuchi, T and Shimizu, M and Maejima, Y and Amiya, E and Tamura, N and Kawaguchi, T and Takahashi, M and Setoh, K and Ohmura, K and Watanabe, R and Horita, T and Atsumi, T and Matsukura, M and Miyata, T and Kochi, Y and Suda, T and Tanemoto, K and Meguro, A and Okada, Y and Ogimoto, A and Yamamoto, M and Takahashi, H and Nakayamada, S and Saito, K and Kuwana, M and Mizuki, N and Tabara, Y and Ueda, A and Komuro, I and Kimura, A and Isobe, M and Mimori, T and Matsuda, F}, title = {Genetic determinants and an epistasis of LILRA3 and HLA-B*52 in Takayasu arteritis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13045-13050}, doi = {10.1073/pnas.1808850115}, pmid = {30498034}, issn = {1091-6490}, abstract = {Takayasu arteritis (TAK) is a systemic vasculitis with severe complications that affects the aorta and its large branches. HLA-B*52 is an established susceptibility locus to TAK. To date, there are still only a limited number of reports concerning non-HLA susceptibility loci to TAK. We conducted a genome-wide association study (GWAS) and a follow-up study in a total of 633 TAK cases and 5,928 controls. A total of 510,879 SNPs were genotyped, and 5,875,450 SNPs were imputed together with HLA-B*52. Functional annotation of significant loci, enhancer enrichment, and pathway analyses were conducted. We identified four unreported significant loci, namely rs2322599, rs103294, rs17133698, and rs1713450, in PTK2B, LILRA3/LILRB2, DUSP22, and KLHL33, respectively. Two additional significant loci unreported in non-European GWAS were identified, namely HSPA6/FCGR3A and chr21q.22. We found that a single variant associated with the expression of MICB, a ligand for natural killer (NK) cell receptor, could explain the entire association with the HLA-B region. Rs2322599 is strongly associated with the expression of PTK2B Rs103294 risk allele in LILRA3/LILRB2 is known to be a tagging SNP for the deletion of LILRA3, a soluble receptor of HLA class I molecules. We found a significant epistasis effect between HLA-B*52 and rs103294 (P = 1.2 × 10-3). Enhancer enrichment analysis and pathway analysis suggested the involvement of NK cells (P = 8.8 × 10-5, enhancer enrichment). In conclusion, four unreported TAK susceptibility loci and an epistasis effect between LILRA3 and HLA-B*52 were identified. HLA and non-HLA regions suggested a critical role for NK cells in TAK.}, } @article {pmid30498033, year = {2018}, author = {Atretkhany, KN and Mufazalov, IA and Dunst, J and Kuchmiy, A and Gogoleva, VS and Andruszewski, D and Drutskaya, MS and Faustman, DL and Schwabenland, M and Prinz, M and Kruglov, AA and Waisman, A and Nedospasov, SA}, title = {Intrinsic TNFR2 signaling in T regulatory cells provides protection in CNS autoimmunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13051-13056}, doi = {10.1073/pnas.1807499115}, pmid = {30498033}, issn = {1091-6490}, abstract = {TNF is a multifunctional cytokine involved in autoimmune disease pathogenesis that exerts its effects through two distinct TNF receptors, TNFR1 and TNFR2. While TNF- and TNFR1-deficient (but not TNFR2-deficient) mice show very similar phenotypes, the significance of TNFR2 signaling in health and disease remains incompletely understood. Recent studies implicated the importance of the TNF/TNFR2 axis in T regulatory (Treg) cell functions. To definitively ascertain the significance of TNFR2 signaling, we generated and validated doubly humanized TNF/TNFR2 mice, with the option of conditional inactivation of TNFR2. These mice carry a functional human TNF-TNFR2 (hTNF-hTNFR2) signaling module and provide a useful tool for comparative evaluation of TNF-directed biologics. Conditional inactivation of TNFR2 in FoxP3+ cells in doubly humanized TNF/TNFR2 mice down-regulated the expression of Treg signature molecules (such as FoxP3, CD25, CTLA-4, and GITR) and diminished Treg suppressive function in vitro. Consequently, Treg-restricted TNFR2 deficiency led to significant exacerbation of experimental autoimmune encephalomyelitis (EAE), accompanied by reduced capacity to control Th17-mediated immune responses. Our findings expose the intrinsic and beneficial effects of TNFR2 signaling in Treg cells that could translate into protective functions in vivo, including treatment of autoimmunity.}, } @article {pmid30498032, year = {2018}, author = {Wang, H and Liu, F and Chen, W and Sun, X and Cui, W and Dong, Z and Zhao, K and Zhang, H and Li, H and Xing, G and Fei, E and Pan, BX and Li, BM and Xiong, WC and Mei, L}, title = {Genetic recovery of ErbB4 in adulthood partially restores brain functions in null mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13105-13110}, doi = {10.1073/pnas.1811287115}, pmid = {30498032}, issn = {1091-6490}, abstract = {Neurotrophic factor NRG1 and its receptor ErbB4 play a role in GABAergic circuit assembly during development. ErbB4 null mice possess fewer interneurons, have decreased GABA release, and show impaired behavior in various paradigms. In addition, NRG1 and ErbB4 have also been implicated in regulating GABAergic transmission and plasticity in matured brains. However, current ErbB4 mutant strains are unable to determine whether phenotypes in adult mutant mice result from abnormal neural development. This important question, a glaring gap in understanding NRG1-ErbB4 function, was addressed by using two strains of mice with temporal control of ErbB4 deletion and expression, respectively. We found that ErbB4 deletion in adult mice impaired behavior and GABA release but had no effect on neuron numbers and morphology. On the other hand, some deficits due to the ErbB4 null mutation during development were alleviated by restoring ErbB4 expression at the adult stage. Together, our results indicate a critical role of NRG1-ErbB4 signaling in GABAergic transmission and behavior in adulthood and suggest that restoring NRG1-ErbB4 signaling at the postdevelopmental stage might benefit relevant brain disorders.}, } @article {pmid30498031, year = {2018}, author = {Matsunuma, R and Chan, DW and Kim, BJ and Singh, P and Han, A and Saltzman, AB and Cheng, C and Lei, JT and Wang, J and Roberto da Silva, L and Sahin, E and Leng, M and Fan, C and Perou, CM and Malovannaya, A and Ellis, MJ}, title = {DPYSL3 modulates mitosis, migration, and epithelial-to-mesenchymal transition in claudin-low breast cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11978-E11987}, doi = {10.1073/pnas.1810598115}, pmid = {30498031}, issn = {1091-6490}, support = {U54 CA233223/CA/NCI NIH HHS/United States ; R01 CA148761/CA/NCI NIH HHS/United States ; UL1 RR024992/RR/NCRR NIH HHS/United States ; P50 CA058223/CA/NCI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; U24 CA143848/CA/NCI NIH HHS/United States ; R01 CA182467/CA/NCI NIH HHS/United States ; U01 CA214125/CA/NCI NIH HHS/United States ; U24 CA160035/CA/NCI NIH HHS/United States ; T32 GM088129/GM/NIGMS NIH HHS/United States ; }, abstract = {A Clinical Proteomic Tumor Analysis Consortium (CPTAC) proteogenomic analysis prioritized dihydropyrimidinase-like-3 (DPYSL3) as a multilevel (RNA/protein/phosphoprotein) expression outlier specific to the claudin-low (CLOW) subset of triple-negative breast cancers. A PubMed informatics tool indicated a paucity of data in the context of breast cancer, which further prioritized DPYSL3 for study. DPYSL3 knockdown in DPYSL3-positive ([Formula: see text]) CLOW cell lines demonstrated reduced proliferation, yet enhanced motility and increased expression of epithelial-to-mesenchymal transition (EMT) markers, suggesting that DPYSL3 is a multifunctional signaling modulator. Slower proliferation in DPYSL3-negative ([Formula: see text]) CLOW cells was associated with accumulation of multinucleated cells, indicating a mitotic defect that was associated with a collapse of the vimentin microfilament network and increased vimentin phosphorylation. DPYSL3 also suppressed the expression of EMT regulators SNAIL and TWIST and opposed p21 activated kinase 2 (PAK2)-dependent migration. However, these EMT regulators in turn induce DPYSL3 expression, suggesting that DPYSL3 participates in negative feedback on EMT. In conclusion, DPYSL3 expression identifies CLOW tumors that will be sensitive to approaches that promote vimentin phosphorylation during mitosis and inhibitors of PAK signaling during migration and EMT.}, } @article {pmid30498030, year = {2018}, author = {Baba, K and Piano, I and Lyuboslavsky, P and Chrenek, MA and Sellers, JT and Zhang, S and Gargini, C and He, L and Tosini, G and Iuvone, PM}, title = {Removal of clock gene Bmal1 from the retina affects retinal development and accelerates cone photoreceptor degeneration during aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13099-13104}, doi = {10.1073/pnas.1808137115}, pmid = {30498030}, issn = {1091-6490}, support = {G12 MD007602/MD/NIMHD NIH HHS/United States ; R01 EY026291/EY/NEI NIH HHS/United States ; R01 EY004864/EY/NEI NIH HHS/United States ; P30 EY006360/EY/NEI NIH HHS/United States ; }, abstract = {The mammalian retina contains an autonomous circadian clock system that controls many physiological functions within this tissue. Previous studies on young mice have reported that removal of the key circadian clock gene Bmal1 from the retina affects the circadian regulation of visual function, but does not affect photoreceptor viability. Because dysfunction in the circadian system is known to affect cell viability during aging in other systems, we compared the effect of Bmal1 removal from the retina on visual function, inner retinal structure, and photoreceptor viability in young (1 to 3 months) and aged (24 to 26 months) mice. We found that removal of Bmal1 from the retina significantly affects visual information processing in both rod and cone pathways, reduces the thickness of inner retinal nuclear and plexiform layers, accelerates the decline of visual functions during aging, and reduces the viability of cone photoreceptors. Our results thus suggest that circadian clock dysfunction, caused by genetic or other means, may contribute to the decline of visual function during development and aging.}, } @article {pmid30498029, year = {2018}, author = {Crombie, AT and Larke-Mejia, NL and Emery, H and Dawson, R and Pratscher, J and Murphy, GP and McGenity, TJ and Murrell, JC}, title = {Poplar phyllosphere harbors disparate isoprene-degrading bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13081-13086}, doi = {10.1073/pnas.1812668115}, pmid = {30498029}, issn = {1091-6490}, abstract = {The climate-active gas isoprene (2-methyl-1,3-butadiene) is released to the atmosphere in huge quantities, almost equaling that of methane, yet we know little about the biological cycling of isoprene in the environment. Although bacteria capable of growth on isoprene as the sole source of carbon and energy have previously been isolated from soils and sediments, no microbiological studies have targeted the major source of isoprene and examined the phyllosphere of isoprene-emitting trees for the presence of degraders of this abundant carbon source. Here, we identified isoprene-degrading bacteria in poplar tree-derived microcosms by DNA stable isotope probing. The genomes of isoprene-degrading taxa were reconstructed, putative isoprene metabolic genes were identified, and isoprene-related gene transcription was analyzed by shotgun metagenomics and metatranscriptomics. Gram-positive bacteria of the genus Rhodococcus proved to be the dominant isoprene degraders, as previously found in soil. However, a wider diversity of isoprene utilizers was also revealed, notably Variovorax, a genus not previously associated with this trait. This finding was confirmed by expression of the isoprene monooxygenase from Variovorax in a heterologous host. A Variovorax strain that could grow on isoprene as the sole carbon and energy source was isolated. Analysis of its genome confirmed that it contained isoprene metabolic genes with an identical layout and high similarity to those identified by DNA-stable isotope probing and metagenomics. This study provides evidence of a wide diversity of isoprene-degrading bacteria in the isoprene-emitting tree phyllosphere and greatly enhances our understanding of the biodegradation of this important metabolite and climate-active gas.}, } @article {pmid30498028, year = {2018}, author = {Fernández-Coll, L and Potrykus, K and Cashel, M}, title = {Puzzling conformational changes affecting proteins binding to the RNA polymerase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12550-12552}, doi = {10.1073/pnas.1818361115}, pmid = {30498028}, issn = {1091-6490}, mesh = {Biophysical Phenomena ; *DNA-Directed RNA Polymerases ; Oxidation-Reduction ; *RNA, Bacterial ; }, } @article {pmid30498027, year = {2018}, author = {Phan, TV and Morris, RJ and Lam, HT and Hulamm, P and Black, ME and Bos, J and Austin, RH}, title = {Emergence of Escherichia coli critically buckled motile helices under stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12979-12984}, doi = {10.1073/pnas.1809374115}, pmid = {30498027}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Bacteria under external stress can reveal unexpected emergent phenotypes. We show that the intensely studied bacterium Escherichia coli can transform into long, highly motile helical filaments poized at a torsional buckling criticality when exposed to minimum inhibitory concentrations of several antibiotics. While the highly motile helices are physically either right- or left-handed, the motile helices always rotate with a right-handed angular velocity [Formula: see text], which points in the same direction as the translational velocity [Formula: see text] of the helix. Furthermore, these helical cells do not swim by a "run and tumble" but rather synchronously flip their spin [Formula: see text] and thus translational velocity-backing up rather than tumbling. By increasing the translational persistence length, these dynamics give rise to an effective diffusion coefficient up to 20 times that of a normal E. coli cell. Finally, we propose an evolutionary mechanism for this phenotype's emergence whereby the increased effective diffusivity provides a fitness advantage in allowing filamentous cells to more readily escape regions of high external stress.}, } @article {pmid30497920, year = {2019}, author = {Botella, H and Vaubourgeix, J}, title = {Building Walls: Work That Never Ends.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {4-7}, doi = {10.1016/j.tim.2018.11.006}, pmid = {30497920}, issn = {1878-4380}, abstract = {Fluorescent amino acid analogs have proven to be useful tools for studying the dynamics of peptidoglycan metabolism. García-Heredia and colleagues showed that their route of incorporation differs depending on the adjunct fluorophore and applied this property to investigate mycobacterial peptidoglycan synthesis and remodeling with heightened granularity.}, } @article {pmid30497919, year = {2019}, author = {Eisenhofer, R and Minich, JJ and Marotz, C and Cooper, A and Knight, R and Weyrich, LS}, title = {Contamination in Low Microbial Biomass Microbiome Studies: Issues and Recommendations.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {105-117}, doi = {10.1016/j.tim.2018.11.003}, pmid = {30497919}, issn = {1878-4380}, abstract = {Next-generation sequencing approaches in microbiome research have allowed surveys of microbial communities, their genomes, and their functions with higher sensitivity than ever before. However, this sensitivity is a double-edged sword because these tools also efficiently detect contaminant DNA and cross-contamination, which can confound the interpretation of microbiome data. Therefore, there is an urgent need to integrate key controls into microbiome research to improve the integrity of microbiome studies. Here, we review how contaminant DNA and cross-contamination arise within microbiome studies and discuss their negative impacts, especially during the analysis of low microbial biomass samples. We then identify several key measures that researchers can implement to reduce the impact of contaminant DNA and cross-contamination during microbiome research. We put forward a set of minimal experimental criteria, the 'RIDE' checklist, to improve the validity of future low microbial biomass research.}, } @article {pmid30497791, year = {2018}, author = {Smith, AB and Godsoe, W and Rodríguez-Sánchez, F and Wang, HH and Warren, D}, title = {Niche Estimation Above and Below the Species Level.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2018.10.012}, pmid = {30497791}, issn = {1872-8383}, abstract = {Ecological niches reflect not only adaptation to local circumstances but also the tendency of related lineages to share environmental tolerances. As a result, information on phylogenetic relationships has underappreciated potential to inform ecological niche modeling. Here we review three strategies for incorporating evolutionary information into niche models: splitting lineages into subunits, lumping across lineages, and partial pooling of lineages into a common statistical framework that implicitly or explicitly accounts for evolutionary relationships. We challenge the default practice of modeling at the species level, which ignores the process of niche evolution and erroneously assumes that the species is always the appropriate level for niche estimation. Progress in the field requires reexamination of how we assess models of niches versus models of distributions.}, } @article {pmid30497682, year = {2018}, author = {Morse, PE and Chester, SGB and Boyer, DM and Smith, T and Smith, R and Gigase, P and Bloch, JI}, title = {New fossils, systematics, and biogeography of the oldest known crown primate Teilhardina from the earliest Eocene of Asia, Europe, and North America.}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2018.08.005}, pmid = {30497682}, issn = {1095-8606}, abstract = {Omomyiform primates are among the most basal fossil haplorhines, with the oldest classified in the genus Teilhardina and known contemporaneously from Asia, Europe, and North America during the Paleocene-Eocene Thermal Maximum (PETM) ∼56 mya. Characterization of morphology in this genus has been limited by small sample sizes and fragmentary fossils. A new dental sample (n = 163) of the North American species Teilhardina brandti from PETM strata of the Bighorn Basin, Wyoming, documents previously unknown morphology and variation, prompting the need for a systematic revision of the genus. The P4 of T. brandti expresses a range of variation that encompasses that of the recently named, slightly younger North American species 'Teilhardina gingerichi,' which is here synonymized with T. brandti. A new partial dentary preserving the alveoli for P1-2 demonstrates that T. brandti variably expresses an unreduced, centrally-located P1, and in this regard is similar to that of T. asiatica from China. This observation, coupled with further documentation of variability in P1 alveolar size, position, and presence in the European type species T. belgica, indicates that the original diagnosis of T. asiatica is insufficient at distinguishing this species from either T. belgica or T. brandti. Likewise, the basal omomyiform 'Archicebus achilles' requires revision to be distinguished from Teilhardina. Results from a phylogenetic analysis of 1890 characters scored for omomyiforms, adapiforms, and other euarchontan mammals produces a novel clade including T. magnoliana, T. brandti, T. asiatica, and T. belgica to the exclusion of two species previously referred to Teilhardina, which are here classified in a new genus (Bownomomys americanus and Bownomomys crassidens). While hypotheses of relationships and inferred biogeographic patterns among species of Teilhardina could change with the discovery of more complete fossils, the results of these analyses indicate a similar probability that the genus originated in either Asia or North America.}, } @article {pmid30497588, year = {2018}, author = {Castellane, A and Paternotte, C}, title = {Knowledge transfer without knowledge? The case of agentive metaphors in biology.}, journal = {Studies in history and philosophy of science}, volume = {72}, number = {}, pages = {49-58}, doi = {10.1016/j.shpsa.2018.05.002}, pmid = {30497588}, issn = {0039-3681}, abstract = {Are scientific metaphors dispensable shortcuts that encapsulate knowledge but can always be translated back? Or do they constitute cases of knowledge transfer, even if seemingly based on scientifically underdeveloped domains? This paper defends the latter view. By drawing on the linguistic theories of metaphors, we assess a variety of agentive metaphors that pervade biology. Intentional metaphors are found unsatisfying because their use is either rigid or too widely flexible. By contrast, rational agent metaphors constitute good scientific metaphors, displaying flexible use and heuristic fruitfulness. Their range of application constantly evolves because they provide guidelines that permit the exploration of the applicability of source domain in a target domain. Their unique heuristic value makes them akin to research programs and allows for knowledge transfer, because they are based on a proper scientific source domain rather than on a folk or underdeveloped one.}, } @article {pmid30497587, year = {2018}, author = {Cunha, IFD}, title = {Constructing dystopian experience: A Neurath-Cartwrightian approach to the philosophy of social technology.}, journal = {Studies in history and philosophy of science}, volume = {72}, number = {}, pages = {41-48}, doi = {10.1016/j.shpsa.2018.05.012}, pmid = {30497587}, issn = {0039-3681}, abstract = {Social situations, the object of the social sciences, are complex and unique: they contain so many variable aspects that they cannot be reproduced, and it is even difficult to experience two situations that are alike in many respects. The social scientists' past experiences that serve as their background knowledge to intervene in an existent situation is poor compared to what a traditional epistemologist would consider ideal. A way of dealing with the variable and insufficient background of social scientists is by means of models. But, then, how should we characterize social scientific models? This paper examines Otto Neurath's scientific utopianism as an attempt to deal with this problem. Neurath proposes that social scientists work with utopias: broad imaginative plans that coordinate a multitude of features of a social situation. This notion can be used in current debates in philosophy of science because we notice that utopias, in Neurath's sense, are comparable to models and nomological machines in Nancy Cartwright's conception. A model-based view of science lays emphasis on the fact that scientists learn from the repeated operation of such abstract entities, just as they learn from the repetition of experiments in a laboratory. Hence this approach suggests an approximation between the natural and the social sciences, as well as between science and utopian literature. This is exemplified by analyzing the literary dystopia We, written by Yevgeny Zamyatin, to show that reasoning from and debating about utopian writings, even if fictional and pessimistic, creates phenomena of valuation, which are fundamental for constituting a background of experiences in the social sciences.}, } @article {pmid30497586, year = {2018}, author = {Colaço, D}, title = {Rip it up and start again: The rejection of a characterization of a phenomenon.}, journal = {Studies in history and philosophy of science}, volume = {72}, number = {}, pages = {32-40}, doi = {10.1016/j.shpsa.2018.04.003}, pmid = {30497586}, issn = {0039-3681}, abstract = {In this paper, I investigate the nature of empirical findings that provide evidence for the characterization of a scientific phenomenon, and the defeasible nature of this evidence. To do so, I explore an exemplary instance of the rejection of a characterization of a scientific phenomenon: memory transfer. I examine the reason why the characterization of memory transfer was rejected, and analyze how this rejection tied to researchers' failures to resolve experimental issues relating to replication and confounds. I criticize the presentation of the case by Harry Collins and Trevor Pinch, who claim that no sufficient reason was provided to abandon research on memory transfer. I argue that skeptics about memory transfer adopted what I call a defeater strategy, in which researchers exploit the defeasibility of the evidence for a characterization of a phenomenon.}, } @article {pmid30497585, year = {2018}, author = {Statham, G}, title = {Mechanisms, the interventionist theory, and the ability to use causal relationships.}, journal = {Studies in history and philosophy of science}, volume = {72}, number = {}, pages = {22-31}, doi = {10.1016/j.shpsa.2018.04.002}, pmid = {30497585}, issn = {0039-3681}, abstract = {In the area of social science, in particular, although we have developed methods for reliably discovering the existence of causal relationships, we are not very good at using these to design effective social policy. Cartwright argues that in order to improve our ability to use causal relationships, it is essential to develop a theory of causation that makes explicit the connections between the nature of causation, our best methods for discovering causal relationships, and the uses to which these are put. I argue that Woodward's interventionist theory of causation is uniquely suited to meet Cartwright's challenge. More specifically, interventionist mechanisms can provide the bridge from 'hunting causes' to 'using them', if interventionists (i) tell us more about the nature of these mechanisms, and (ii) endorse the claim that it is these mechanisms-or whatever constitutes them-that make causal claims true. I illustrate how having an understanding of interventionist mechanisms can allow us to put causal knowledge to use via a detailed example from organic chemistry.}, } @article {pmid30497584, year = {2018}, author = {Lisciandra, C}, title = {The role of psychology in behavioral economics: The case of social preferences.}, journal = {Studies in history and philosophy of science}, volume = {72}, number = {}, pages = {11-21}, doi = {10.1016/j.shpsa.2018.01.010}, pmid = {30497584}, issn = {0039-3681}, abstract = {Behavioral economics is a field of study that is often thought of as interdisciplinary, insofar as it uses psychological insights to inform economic models. Yet the level of conceptual and methodological exchange between the two disciplines is disputed in the literature. On the one hand, behavioral economic models are often presented as psychologically informed models of individual decision-making (Camerer & Loewenstein, 2003). On the other hand, these models have often been criticized for being merely more elaborated "as if" economic models (Berg & Gigerenzer, 2010). The aim of this paper is to contribute to this debate by looking at a central topic in behavioral economics: the case of social preferences. Have findings or research methods been exchanged between psychology and economics in this research area? Have scientists with different backgrounds "travelled" across domains, thus transferring their expertise from one discipline to another? By addressing these and related questions, this paper will assess the level of knowledge transfer between psychology and economics in the study of social preferences.}, } @article {pmid30497583, year = {2018}, author = {O'Malley, MA and Parke, EC}, title = {Microbes, mathematics, and models.}, journal = {Studies in history and philosophy of science}, volume = {72}, number = {}, pages = {1-10}, doi = {10.1016/j.shpsa.2018.07.001}, pmid = {30497583}, issn = {0039-3681}, abstract = {Microbial model systems have a long history of fruitful use in fields that include evolution and ecology. In order to develop further insight into modelling practice, we examine how the competitive exclusion and coexistence of competing species have been modelled mathematically and materially over the course of a long research history. In particular, we investigate how microbial models of these dynamics interact with mathematical or computational models of the same phenomena. Our cases illuminate the ways in which microbial systems and equations work as models, and what happens when they generate inconsistent findings about shared targets. We reveal an iterative strategy of comparative modelling in different media, and suggest reasons why microbial models have a special degree of epistemic tractability in multimodel inquiry.}, } @article {pmid30497531, year = {2018}, author = {Kumagai, H and Yoshioka, T and Sugaya, H and Tomaru, Y and Shimizu, Y and Yamazaki, M and Mishima, H}, title = {Quantitative assessment of mesenchymal stem cells contained in concentrated autologous bone marrow aspirate transplantation for the treatment of osteonecrosis of the femoral head: predictive factors and differences by etiology.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {848}, pmid = {30497531}, issn = {1756-0500}, abstract = {OBJECTIVE: We previously established concentrated autologous bone marrow aspirate transplantation as a one-step, lowly invasive, joint-preserving surgical technique for treating osteonecrosis of the femoral head. The objectives of this study were to identify factors that may predict the mesenchymal stem cell (MSC) count in bone marrow aspirate, concentrated using our method, and to clarify etiology related differences in the number of MSCs in concentrated bone marrow aspirate.

RESULTS: The MSC counts per 106 nucleated cells before concentration in the steroid, alcohol, and trauma groups were 2.31 ± 2.96, 2.58 ± 2.30, and 1.95 ± 1.85, respectively. The MSC counts per 106 nucleated cells after concentration were 3.23 ± 3.41, 3.30 ± 2.83, and 2.56 ± 1.98 cells, respectively. The MSC concentration rates in the steroid, alcohol, and trauma groups were 7.15 ± 5.62, 5.08 ± 1.96, and 8.23 ± 4.82 times, respectively. None of the differences were significant. Multiple regression analysis revealed that MSC count was related to the total bone marrow aspirated, peripheral blood platelet count, and nucleated cell count in the initial aspiration.}, } @article {pmid30497525, year = {2018}, author = {Yadeta, TA}, title = {Antenatal care utilization increase the odds of women knowledge on neonatal danger sign: a community-based study, eastern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {845}, pmid = {30497525}, issn = {1756-0500}, abstract = {OBJECTIVE: This study, aimed to determine women knowledge on key neonatal dander sign and associated factors among women recently gave birth in eastern Ethiopia.

RESULTS: Of the 757 women interviewed, fever was reported as a neonatal danger sign by 255 (33.7%) followed by poor sucking (24.8%), difficulty breathing (23.5%), convulsion (16.0%), lethargy (12.9%), a very small baby (11.8%) and hypothermia (2.9%). Overall 9.38% listed four or more danger signs spontaneously. Attending at least one antenatal care visit [AOR = 2.83; 95% CI (1.62, 4.93)], and giving birth at health facilities [AOR = 3.31; 95% CI (1.67, 6.53)] were significantly associated with knowledge of neonatal danger signs.}, } @article {pmid30497517, year = {2018}, author = {Lam, TH and Verzotto, D and Brahma, P and Ng, AHQ and Hu, P and Schnell, D and Tiesman, J and Kong, R and Ton, TMU and Li, J and Ong, M and Lu, Y and Swaile, D and Liu, P and Liu, J and Nagarajan, N}, title = {Understanding the microbial basis of body odor in pre-pubescent children and teenagers.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {213}, pmid = {30497517}, issn = {2049-2618}, support = {APG2013/032//Agency for Science, Technology and Research/ ; }, abstract = {BACKGROUND: Even though human sweat is odorless, bacterial growth and decomposition of specific odor precursors in it is believed to give rise to body odor in humans. While mechanisms of odor generation have been widely studied in adults, little is known for teenagers and pre-pubescent children who have distinct sweat composition from immature apocrine and sebaceous glands, but are arguably more susceptible to the social and psychological impact of malodor.

RESULTS: We integrated information from whole microbiome analysis of multiple skin sites (underarm, neck, and head) and multiple time points (1 h and 8 h after bath), analyzing 180 samples in total to perform the largest metagenome-wide association study to date on malodor. Significant positive correlations were observed between odor intensity and the relative abundance of Staphylococcus hominis, Staphylococcus epidermidis, and Cutibacterium avidum, as well as negative correlation with Acinetobacter schindleri and Cutibacterium species. Metabolic pathway analysis highlighted the association of isovaleric and acetic acid production (sour odor) from enriched S. epidermidis (teen underarm) and S. hominis (child neck) enzymes and sulfur production from Staphylococcus species (teen underarm) with odor intensity, in good agreement with observed odor characteristics in pre-pubescent children and teenagers. Experiments with cultures on human and artificial sweat confirmed the ability of S. hominis and S. epidermidis to independently produce malodor with distinct odor characteristics.

CONCLUSIONS: These results showcase the power of skin metagenomics to study host-microbial co-metabolic interactions, identifying distinct pathways for odor generation from sweat in pre-pubescent children and teenagers and highlighting key enzymatic targets for intervention.}, } @article {pmid30497514, year = {2018}, author = {Moffat, CS and Stoll, T and Moolhuijzen, P}, title = {Proteomics of the wheat tan spot pathogen Pyrenophora tritici-repentis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {846}, pmid = {30497514}, issn = {1756-0500}, support = {CUR00023//Grains Research and Development Corporation/ ; }, abstract = {OBJECTIVES: The fungus Pyrenophora tritici-repentis is a major pathogen of wheat worldwide, causing the leaf spotting disease tan spot. To best inform approaches for plant genetic resistance, an understanding of the biology and pathogenicity mechanisms of this fungal pathogen is essential. Here, intracellular and extracellular proteins of P. tritici-repentis were extracted, and peptides analysed via high-resolution mass spectrometry. Our objective was to generate a useful proteomics resource for P. tritici-repentis. A survey of proteins secreted by the pathogen into culture filtrate is especially useful, as these are likely to come in direct contact with the wheat host and may play important roles in infection/pathogenicity. The peptide data presented herein, has also been used to successfully verify and refine in silico predicted P. tritici-repentis gene annotations, through the validation of alternative splicing and reading frame shifts.

DATA DESCRIPTION: The data sets presented consist of peptide spectra of the extracellular and intracellular proteomes of three P. tritici-repentis isolates. Peptide matches to translated transcripts of the North American reference isolate Pt-1C-BFP are also provided.}, } @article {pmid30497510, year = {2018}, author = {Lea, CS and Bohra, S and Moore, T and Passwater, C and Liles, D}, title = {Exploring behaviors, treatment beliefs, and barriers to oral chemotherapy adherence among adult leukemia patients in a rural outpatient setting.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {843}, pmid = {30497510}, issn = {1756-0500}, support = {10896127//National Comprehensive Cancer Network and Pfizer Independent Grants for Learning and Change/ ; }, abstract = {OBJECTIVE: Adherence to oral chemotherapy is essential for patients with chronic myeloid leukemia (CML) and multiple myeloma (MM) to remain in remission. Few studies have used a Likert-type scale to measure medication adherence in CML and MM patients. We applied a validated treatment adherence tool, the ASK-12 (Adherence Starts with Knowledge®) survey, which assessed inconvenience and forgetfulness, treatment beliefs, and medication-taking behaviors recorded on a five-point Likert-type scale at two visits.

RESULTS: A medication adherence survey was administered to 42 newly diagnosed or pre-existing CML or MM patients at two outpatient oncology clinics affiliated with an academic medical center in rural eastern North Carolina. Thirty-one patients completed surveys at visit 1 and visit 2 (median 4.5 months apart). Most patients were treated for MM (65%), were non-Hispanic black (68%) and female (58%). Within subscales, mean adherence scores decreased between visits, signaling better adherence. Overall, visit scores were correlated (0.63, p = 0.001). Forgetting to take medication sometimes was the most common reason for non-adherence. Medication costs were not a barrier for MM patients. Greater patient-provider informed decision-making was identified as an opportunity for quality improvement among CML patients. The ASK-12 survey provided a strategy to obtain robust information on medication adherence.}, } @article {pmid30497507, year = {2018}, author = {Kietsiriroje, N and Kanjanahirun, K and Kwankaew, J and Ponrak, R and Soonthornpun, S}, title = {Phytosterols and inulin-enriched soymilk increases glucagon-like peptide-1 secretion in healthy men: double-blind randomized controlled trial, subgroup study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {844}, pmid = {30497507}, issn = {1756-0500}, abstract = {OBJECTIVE: The study aimed to determine the effect of phytosterols and inulin on plasma glucose, insulin, and GLP-1 levels among healthy men after consuming phytosterols and inulin-enriched soymilk for 8 weeks.

RESULTS: A total of 26 men at least 20 years old were randomly assigned into the 2 g/day of phytosterols and 10 g/day of inulin-enriched soymilk (intervention) group or into the standard soymilk (control) group. In the intervention group, the area under the curve of Glucagon-like peptide-1 secretion increased significantly, compared to its baseline (p = 0.003). The area under the curve of insulin secretion also increased but it did not meet statistical significance (p = 0.118). The area under the curves of plasma glucose were similar between pre- and post-test (p = 0.348). In the control group, none of the primary results significantly changed compared to their baseline levels. Trial registration Thai Clinical Trial Registry: TCTR20160319001 date: March 19, 2016, retrospectively registered.}, } @article {pmid30497485, year = {2018}, author = {Bereded, DT and Salih, MH and Abebe, AE}, title = {Prevalence and risk factors of pressure ulcer in hospitalized adult patients; a single center study from Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {847}, pmid = {30497485}, issn = {1756-0500}, abstract = {OBJECTIVE: The main objective of this study was to assess the prevalence of pressure ulcer and its risk factors among adult hospitalized patients at Dessie Referral Hospital, Northeast Ethiopia, 2016 G.

C RESULT: A cross-sectional institutional based study with a single population proportion formula was used to determine the sample size. The total sample size of 355 patients was distributed proportionally to the respected wards. Every other patient was selected by systematic random sampling technique from each ward with a response rate of 100% A total of 53 patients with pressure ulcer were detected giving the prevalence rate of 14.9%. The lack of regular positioning and activity, friction/shear, and prolonged hospitalization were risk factors for pressure ulcer.}, } @article {pmid30497463, year = {2018}, author = {Walter, T and Zink, R and Laaha, G and Zaller, JG and Heigl, F}, title = {Fox sightings in a city are related to certain land use classes and sociodemographics: results from a citizen science project.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {50}, pmid = {30497463}, issn = {1472-6785}, abstract = {BACKGROUND: Red foxes (Vulpes vulpes L.) have become successful inhabitants of urban areas in recent years. However, our knowledge about the occurrence, distribution and association with land uses of these urban foxes is poor, partly because many favoured habitats are on private properties and therefore hardly accessible to scientists. We assumed that citizen science, i.e. the involvement of the public, could enable researchers to bridge this information gap. We analysed 1179 fox sightings in the city of Vienna, Austria reported via citizen science projects to examine relationships between foxes and the surrounding land use classes as well as sociodemographic parameters.

RESULTS: Conditional probabilities of encountering foxes were substantially higher in gardens, areas with a low building density, parks or squares as compared to agricultural areas, industrial areas or forests. Generalized linear model analyses showed that sociodemographic parameters such as education levels, district area, population density and average household income additionally improved the predictability of fox sightings.

CONCLUSIONS: Reports of fox sightings by citizen scientists might help to support the establishment of wildlife management in cities. Additionally, these data could be used to address public health issues in relation with red foxes as they can carry zoonoses that are also dangerous to humans.}, } @article {pmid30497452, year = {2018}, author = {Foronda, A and Ehlers, BK and Alados, CL and Pueyo, Y}, title = {Species-specific interference exerted by the shrub Cistus clusii Dunal in a semi-arid Mediterranean gypsum plant community.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {49}, pmid = {30497452}, issn = {1472-6785}, support = {BES-2013-063852//Ministerio de Economía y Competitividad/ ; EEBB-I-15-10298//Ministerio de Economía y Competitividad/ ; CGL2012-37508//Ministerio de Economía y Competitividad/ ; CGL2016-80783-R//Ministerio de Economía y Competitividad/ ; }, abstract = {BACKGROUND: The gypsovag shrub Cistus clusii is locally dominant in semi-arid gypsum plant communities of North-Eastern Spain. This species commonly grows in species-poor patches even though it has nurse potential, suggesting interference on neighbouring species. Other Cistus species exert a chemically mediated interference on plant communities, suggesting that it might be a common phenomenon in this genus. This study aimed investigating whether C. clusii exerts chemically mediated interference on neighbouring species in gypsum plant communities. We tested in a greenhouse whether aqueous extracts from C. clusii leaves (L), roots (R) and a mixture of both (RL) affected germination, seedling survival, and growth of nine native species of gypsum communities, including C. clusii itself. We further assessed in the field richness and abundance of plants under the canopy of C. clusii compared to Gypsophila struthium (shrub with a similar architecture having a nurse role) and in open patches. Finally, we specifically assessed in the field the influence of C. clusii on the presence of the species tested in the greenhouse experiment.

RESULTS: Aqueous extracts from C. clusii (R and RL) negatively affected either germination or survival in four of nine species. In the field, richness and abundance of plants were lower under the canopy of C. clusii than under G. struthium, but higher than in open patches. Specifically, five of nine species were less frequent than expected under the canopy of C. clusii.

CONCLUSIONS: Cistus clusii shows species-specific interference with neighbouring species in the community, which may be at least partially attributable to its phytotoxic activity. To our knowledge, this is the first report of species-specific interference by C. clusii.}, } @article {pmid30497415, year = {2018}, author = {Peethambaran, PK and Glenz, R and Höninger, S and Shahinul Islam, SM and Hummel, S and Harter, K and Kolukisaoglu, Ü and Meynard, D and Guiderdoni, E and Nick, P and Riemann, M}, title = {Salt-inducible expression of OsJAZ8 improves resilience against salt-stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {311}, pmid = {30497415}, issn = {1471-2229}, mesh = {Co-Repressor Proteins/genetics/*metabolism/physiology ; Cyclopentanes/metabolism ; Gene Expression Regulation, Plant/drug effects ; Oryza/genetics/*metabolism ; Oxylipins/metabolism ; Plant Growth Regulators/metabolism ; Plant Proteins/genetics/*metabolism/physiology ; Plants, Genetically Modified/genetics ; Salt Stress ; Salt-Tolerant Plants/genetics/*metabolism ; Signal Transduction ; Tobacco/genetics ; }, abstract = {BACKGROUND: Productivity of important crop rice is greatly affected by salinity. The plant hormone jasmonate plays a vital role in salt stress adaptation, but also evokes detrimental side effects if not timely shut down again. As novel strategy to avoid such side effects, OsJAZ8, a negative regulator of jasmonate signalling, is expressed under control of the salt-inducible promoter of the transcription factor ZOS3-11, to obtain a transient jasmonate signature in response to salt stress. To modulate the time course of jasmonate signalling, either a full-length or a dominant negative C-terminally truncated version of OsJAZ8 driven by the ZOS3-11 promoter were expressed in a stable manner either in tobacco BY-2 cells, or in japonica rice.

RESULTS: The transgenic tobacco cells showed reduced mortality and efficient cycling under salt stress adaptation. This was accompanied by reduced sensitivity to Methyl jasmonate and increased responsiveness to auxin. In the case of transgenic rice, the steady-state levels of OsJAZ8 transcripts were more efficiently induced under salt stress compared to the wild type, this induction was more pronounced in the dominant-negative OsJAZ8 variant.

CONCLUSIONS: The result concluded that, more efficient activation of OsJAZ8 was accompanied by improved salt tolerance of the transgenic seedlings and demonstrates the impact of temporal signatures of jasmonate signalling for stress tolerance.}, } @article {pmid30497411, year = {2018}, author = {Zheng, H and Chen, J and Mu, C and Makumbi, D and Xu, Y and Mahuku, G}, title = {Combined linkage and association mapping reveal QTL for host plant resistance to common rust (Puccinia sorghi) in tropical maize.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {310}, pmid = {30497411}, issn = {1471-2229}, support = {OPPGD1390//Bill and Melinda Gates Foundation/ ; }, mesh = {Basidiomycota ; Chromosome Mapping/methods ; Chromosomes, Plant/genetics ; Disease Resistance/*genetics ; Genes, Plant/genetics ; Plant Diseases/immunology/*microbiology ; Quantitative Trait Loci/*genetics ; Zea mays/*genetics/immunology/microbiology ; }, abstract = {BACKGROUND: Common rust, caused by Puccinia sorghi, is an important foliar disease of maize that has been associated with up to 50% grain yield loss. Development of resistant maize germplasm is the ideal strategy to combat P. sorghi.

RESULTS: Association mapping performed using a mixed linear model (MLM), integrating population structure and family relatedness identified 25 QTL (P < 3.12 × 10- 5) that were associated with resistance to common rust and distributed on chromosomes 1, 3, 5, 6, 8, and 10. We identified three QTLs associated with all three disease parameters (final disease rating, mean disease rating, and area under disease progress curve) located on chromosomes 1, 3, and 8. A total of 5 QTLs for resistance to common rust were identified in the RIL population. Nine candidate genes located on chromosomes 1, 5, 6, 8, and 10 for resistance to common rust associated loci were identified through detailed annotation.

CONCLUSIONS: Using a diverse set of inbred lines genotyped with high density markers and evaluated for common rust resistance in multiple environments, it was possible to identify QTL significantly associated with resistance to common rust and several candidate genes. The results point to the need for fine mapping common rust resistance by targeting regions identified in common between this study and others using diverse germplasm.}, } @article {pmid30497407, year = {2018}, author = {Pan, J and Li, Z and Wang, Q and Garrell, AK and Liu, M and Guan, Y and Zhou, W and Liu, W}, title = {Comparative proteomic investigation of drought responses in foxtail millet.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {315}, pmid = {30497407}, issn = {1471-2229}, support = {ZR2016CM23//Shandong Provential Natural Science Foundtion/ ; 2016-2018//the Young Talents Training program of Shandong Academy of Agricultural Sciences/ ; 2015ZDJS03001-2//Major in Shandong Province Science and Technology Projects/ ; 2016ZDJS10A03-05//the Shandong Key Research and Development Program/ ; 31401310//National Natural Science Foundation of China/ ; }, mesh = {Blotting, Western ; Chromatography, High Pressure Liquid ; Dehydration ; Gas Chromatography-Mass Spectrometry ; Gene Expression Regulation, Plant ; Plant Proteins/isolation & purification/metabolism/physiology ; Proteomics ; Real-Time Polymerase Chain Reaction ; Setaria Plant/*metabolism/physiology ; }, abstract = {BACKGROUND: Foxtail millet (Setaria italica L. P. Beauv) has been considered as a tractable model crop in recent years due to its short growing cycle, lower amount of repetitive DNA, inbreeding nature, small diploid genome, and outstanding abiotic stress-tolerance characteristics. With modern agriculture facing various adversities, it's urgent to dissect the mechanisms of how foxtail millet responds and adapts to drought and stress on the proteomic-level.

RESULTS: In this research, a total of 2474 differentially expressed proteins were identified by quantitative proteomic analysis after subjecting foxtail millet seedlings to drought conditions. 321 of these 2474 proteins exhibited significant expression changes, including 252 up-regulated proteins and 69 down-regulated proteins. The resulting proteins could then be divided into different categories, such as stress and defense responses, photosynthesis, carbon metabolism, ROS scavenging, protein synthesis, etc., according to Gene Ontology annotation. Proteins implicated in fatty acid and amino acid metabolism, polyamine biosynthesis, hormone metabolism, and cell wall modifications were also identified. These obtained differential proteins and their possible biological functions under drought stress all suggested that various physiological and metabolic processes might function cooperatively to configure a new dynamic homeostasis in organisms. The expression patterns of five drought-responsive proteins were further validated using western blot analysis. The qRT-PCR was also carried out to analyze the transcription levels of 21 differentially expressed proteins. The results showed large inconsistency in the variation between proteins and the corresponding mRNAs, which showed once again that post-transcriptional modification performs crucial roles in regulating gene expression.

CONCLUSION: The results offered a valuable inventory of proteins that may be involved in drought response and adaption, and provided a regulatory network of different metabolic pathways under stress stimulation. This study will illuminate the stress tolerance mechanisms of foxtail millet, and shed some light on crop germplasm breeding and innovation.}, } @article {pmid30497403, year = {2018}, author = {Wei, K and Chen, H}, title = {Comparative functional genomics analysis of bHLH gene family in rice, maize and wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {309}, pmid = {30497403}, issn = {1471-2229}, mesh = {Arabidopsis/genetics/physiology ; Basic Helix-Loop-Helix Transcription Factors/*genetics/physiology ; Conserved Sequence/genetics ; Dehydration ; Gene Expression Regulation, Plant ; Genome, Plant/*genetics/physiology ; Genomics ; Oryza/*genetics/physiology ; Phylogeny ; Plant Diseases/microbiology ; Sequence Alignment ; Transcriptome ; Triticum/*genetics/physiology ; Zea mays/*genetics/physiology ; }, abstract = {BACKGROUND: The basic helix-loop-helix transcription factors play important roles in diverse cellular and molecular processes. Comparative functional genomics can provide powerful approaches to draw inferences about gene function and evolution among species. The comprehensive comparison of bHLH gene family in different gramineous plants has not yet been reported.

RESULTS: In this study, a total of 183, 231 and 571 bHLHs were identified in rice, maize and wheat genomes respectively, and 1154 bHLH genes from the three species and Arabidopsis were classified into 36 subfamilies. Of the identified genes, 110 OsbHLHs, 188 ZmbHLHs and 209 TabHLHs with relatively high mRNA abundances were detected in one or more tissues during development, and some of them exhibited tissue-specific expression such as TabHLH454-459, ZmbHLH099-101 and OsbHLH037 in root, TabHLH559-562, - 046, - 047 and ZmbHLH010, - 072, - 226 in leaf, TabHLH216-221, - 333, - 335, - 340 and OsbHLH005, - 141 in inflorescence, TabHLH081, ZmbHLH139 and OsbHLH144 in seed. Forty five, twenty nine and thirty one differentially expressed bHLHs were respectively detected in wheat, maize and rice under drought stresses using RNA-seq technology. Among them, the expressions of TabHLH046, - 047, ZmbHLH097, - 098, OsbHLH006 and - 185 were strongly induced, whereas TabHLH303, - 562, ZmbHLH155, - 154, OsbHLH152 and - 113 showed significant down-regulation. Twenty two TabHLHs were induced after stripe rust infection at 24 h and nine of them were suppressed at 72 hpi, whereas 28 and 6 TabHLHs exhibited obviously down- and up-regulation after powdery mildew attack respectively. Forty one ZmbHLHs were differentially expressed in response to F. verticillioides infection. Twenty two co-expression modules were identified by the WGCNA, some of which were associated with particular tissue types. And GO enrichment analysis for the modules showed that some TabHLHs were involved in the control of several biological processes, such as tapetal PCD, lipid metabolism, iron absorption, stress responses and signal regulation.

CONCLUSION: The present study identifies the bHLH family in rice, maize and wheat genomes, and detailedly discusses the evolutionary relationships, expression and function of bHLHs. This study provides some novel and detail information about bHLHs, and may facilitate understanding the molecular basis of the plant growth, development and stress physiology.}, } @article {pmid30497392, year = {2018}, author = {Zhang, H and Ali, A and Hou, F and Wu, T and Guo, D and Zeng, X and Wang, F and Zhao, H and Chen, X and Xu, P and Wu, X}, title = {Effects of ploidy variation on promoter DNA methylation and gene expression in rice (Oryza sativa L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {314}, pmid = {30497392}, issn = {1471-2229}, support = {2016HH0044//Department of Sichuan Science and Technology in China/ ; }, mesh = {DNA Methylation/*genetics ; Gene Expression Regulation, Plant/*genetics ; Haploidy ; Microsatellite Repeats/genetics ; Oryza/*genetics/metabolism ; *Ploidies ; Polymorphism, Single Nucleotide/genetics ; Promoter Regions, Genetic/genetics ; Seedlings/genetics/growth & development ; Triploidy ; }, abstract = {BACKGROUND: Polyploidy, or whole-genome duplication (WGD) promotes genetic diversification in plants. However, whether WGD is accompanied by epigenetic regulation especially DNA methylation remains yet elusive. Methylation of different region in genomic DNA play discrete role in gene regulation and developmental processes in plants.

RESULTS: In our study, we used an apomictic rice line (SARII-628) that produces twin seedlings of different ploidy for methylated DNA immunoprecipitation sequencing (MeDIP-seq). We compared the level of methylation and mRNA expression in three different (CG, CHG, and CHH) sequence contexts of promoter region among haploid (1X), diploid (2X), and triploid (3X) seedling. We used MeDIP-Seq analysis of 14 genes to investigate whole genome DNA methylation and found that relative level of DNA methylation across different ploidy was in following order e.g. diploid > triploid > haploid. GO functional classification of differentially methylated genes into 9 comparisons group of promoter, intergenic and intragenic region discovered, these genes were mostly enriched for cellular component, molecular function, and biological process. By the comparison of methylome data, digital gene expression (DGE), mRNA expression profile, and Q-PCR findings LOC_ Os07g31450 and LOC_ Os01g59320 were analyzed for BS-Seq (Bisulphite sequencing).

CONCLUSIONS: We found that (1) The level of the promoter DNA methylation is negatively correlated with gene expression within each ploidy level. (2) Among all ploidy levels, CG sequence context had highest methylation frequency, and demonstrated that the high CG methylation did reduce gene expression change suggesting that DNA methylation exert repressive function and ensure genome stability during WGD. (3) Alteration in ploidy (from diploid to haploid, or diploid to triploid) reveals supreme changes in methylation frequency of CHH sequence context. Our finding will contribute an understanding towards lower stability of CHH sequence context and educate the effect of promoter region methylation during change in ploidy state in rice.}, } @article {pmid30497385, year = {2018}, author = {Liu, L and Li, W and Liu, C and Chen, B and Tian, X and Chen, C and Li, J and Chen, S}, title = {In vivo haploid induction leads to increased frequency of twin-embryo and abnormal fertilization in maize.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {313}, pmid = {30497385}, issn = {1471-2229}, support = {2016YFD0101200//The National Key Research and Development Plan - Maize heterosis utilization technology and creation of strong heterosis maize hybrids/ ; CARS-02-04//The Modern Maize Industry Technology System/ ; }, mesh = {*Fertilization/genetics ; Genetic Variation ; *Haploidy ; Seedlings/genetics ; Seeds/*genetics/physiology ; Zea mays/*genetics/physiology ; }, abstract = {BACKGROUND: In vivo haploid induction (HI) based on Stock6-derived inducer lines has been the most prevalent means of producing haploids. Nevertheless, the biological mechanism of HI is not fully understood, the twin-embryo kernels had been found during haploid induction, which may provide potential evidence for the abnormal double fertilization during HI.

RESULTS: We investigated twin-embryo frequency in progenies of different haploid inducers. Results reveal that increasing the HI potential significantly improved the frequency of twin-embryo kernels. Compared with the average twin-embryo kernel frequency (average frequency = 0.07%) among progenies pollinated by the haploid inducer line CAUHOI, the frequency of twin-embryo was improved to 0.16% in progenies pollinated by the haploid inducer line CAU5. This result was further confirmed by pollinating single hybrid ND5598 with four haploid inducers possessing differentiated HIRs, where twin-embryo frequency was highly correlated with HIR. Among 237 twin-embryo kernels, we identified 30 haploid twin-embryo kernels (12.66%), a frequency which was much greater than the average HI rate for three other inducer lines (frequency range 2-10%). In addition, aneuploids, occurred at high frequency (8 in 41 twin plants). This level of aneuploidy provides new insight into the abnormal double fertilization during HI. Moreover, we observed differences in growth rate between twin plants in the field, as 4.22% of the twin plants grew at a significantly different rate. Both simple sequence repeats markers (SSR) and 3072 SNP-chip genotyping results revealed that > 90% of the twin plants shared the same origin, and the growth difference could be attributed to aneuploidy, competition for nutrients, and possible hormone regulation.

CONCLUSION: These results demonstrate that an enhanced HI ability can increase twin-embryo kernel frequency, and high frequency of both haploid twin-embryo kernels and aneuploidy observed in this research give us new insights to understand the mechanism of both HI and abnormal embryogenesis.}, } @article {pmid30497384, year = {2018}, author = {Herritt, M and Dhanapal, AP and Purcell, LC and Fritschi, FB}, title = {Identification of genomic loci associated with 21chlorophyll fluorescence phenotypes by genome-wide association analysis in soybean.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {312}, pmid = {30497384}, issn = {1471-2229}, mesh = {Chlorophyll/*metabolism ; Fluorescence ; Genes, Plant/genetics ; Genetic Association Studies ; Genome-Wide Association Study ; Photosynthesis/genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci/*genetics ; Soybeans/*genetics/metabolism ; }, abstract = {BACKGROUND: Photosynthesis is able to convert solar energy into chemical energy in the form of biomass, but the efficiency of photosynthetic solar energy conversion is low. Chlorophyll fluorescence measurements are rapid, non-destructive, and can provide a wealth of information about the efficiencies of the photosynthetic light reaction processes. Efforts aimed at assessing genetic variation and/or mapping of genetic loci associated with chlorophyll fluorescence phenotypes have been rather limited.

RESULTS: Evaluation of SoySNP50K iSelect SNP Beadchip data from the 189 genotypes phenotyped in this analysis identified 32,453 SNPs with a minor allele frequency (MAF) ≥ 5%. A total of 288 (non-unique) SNPs were significantly associated with one or more of the 21 chlorophyll fluorescence phenotypes. Of these, 155 were unique SNPs and 100 SNPs were only associated with a single fluorescence phenotype, while 28, 11, 2, and 14 SNPs, were associated with two, three, four and five or more fluorescence phenotypes, respectively. The 288 non-unique SNPs represent 155 unique SNPs that mark 53 loci. The 155 unique SNPs included 27 that were associated with three or more phenotypes, and thus were called multi-phenotype SNPs. These 27 multi-phenotype SNPs marked 13 multi-phenotype loci (MPL) identified by individual SNPs associated with multiple chlorophyll fluorescence phenotypes or by more than one SNP located within 0.5 MB of other multi-phenotype SNPs.

CONCLUSION: A search in the genomic regions highlighted by these 13 MPL identified genes with annotations indicating involvement in photosynthetic light dependent reactions. These, as well as loci associated with only one or two chlorophyll fluorescence traits, should be useful to develop a better understanding of the genetic basis of photosynthetic light dependent reactions as a whole as well as of specific components of the electron transport chain in soybean. Accordingly, additional genetic and physiological analyses are necessary to determine the relevance and effectiveness of the identified loci for crop improvement efforts.}, } @article {pmid30497383, year = {2018}, author = {Abo Alchamlat, S and Farnir, F}, title = {Aggregation of experts: an application in the field of "interactomics" (detection of interactions on the basis of genomic data).}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {445}, pmid = {30497383}, issn = {1471-2105}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Arthritis, Rheumatoid/*genetics ; Computational Biology/*methods ; *Epistasis, Genetic ; Genome-Wide Association Study/*methods ; Genomics/*methods ; Humans ; Models, Genetic ; Phenotype ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Despite the successful mapping of genes involved in the determinism of numerous traits, a large part of the genetic variation remains unexplained. A possible explanation is that the simple models used in many studies might not properly fit the actual underlying situations. Consequently, various methods have attempted to deal with the simultaneous mapping of genomic regions, assuming that these regions might interact, leading to a complex determinism for various traits. Despite some successes, no gold standard methodology has emerged. Actually, combining several interaction mapping methods might be a better strategy, leading to positive results over a larger set of situations. Our work is a step in that direction.

RESULTS: We first have demonstrated why aggregating results from several distinct methods might increase the statistical power while controlling the type I error. We have illustrated the approach using 6 existing methods (namely: MDR, Boost, BHIT, KNN-MDR, MegaSNPHunter and AntEpiSeeker) on simulated and real data sets. We have used a very simple aggregation strategy: a majority vote across the best loci combinations identified by the individual methods. In order to assess the performances of our aggregation approach in problems where most individual methods tend to fail, we have simulated difficult situations where no marginal effects of individual genes exist and where genetic heterogeneity is present. we have also demonstrated the use of the strategy on real data, using a WTCCC dataset on rheumatoid arthritis. Since we have been using simplistic assumptions to infer the expected power of the aggregation method, the actual power we estimated from our simulations has turned out to be a bit smaller than theoretically expected. Results nevertheless have shown that grouping the results of several methods is advantageous in terms of power, accuracy and type I error control. Furthermore, as more methods should become available in the future, using a grouping strategy will become more advantageous since adding more methods seems to improve the performances of the aggregated method.

CONCLUSIONS: The aggregation of methods as a tool to detect genetic interactions is a potentially useful addition to the arsenal used in complex traits analyses.}, } @article {pmid30497381, year = {2018}, author = {Roberts, RE and Powell, D and Wang, T and Hall, MH and Motti, CA and Cummins, SF}, title = {Putative chemosensory receptors are differentially expressed in the sensory organs of male and female crown-of-thorns starfish, Acanthaster planci.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {853}, pmid = {30497381}, issn = {1471-2164}, abstract = {BACKGROUND: Chemosensation is a critical signalling process for all organisms and is achieved through the interaction between chemosensory receptors and their ligands. The Crown-of-thorns starfish, Acanthaster planci species complex (COTS), is a predator of coral polyps and Acanthaster cf. solaris is currently considered to be one of the main drivers of coral loss on the Great Barrier Reef in Queensland, Australia.

RESULTS: This study reveals the presence of putative variant Ionotropic Receptors (IRs) which are differentially expressed in the olfactory organs of COTS. Several other types of G protein-coupled receptors such as adrenergic, metabotropic glutamate, cholecystokinin, trace-amine associated, GRL101 and GPCR52 receptors have also been identified. Several receptors display male-biased expression within the sensory tentacles, indicating possible reproductive significance.

CONCLUSIONS: Many of the receptors identified in this study may have a role in reproduction and are therefore key targets for further investigation. Based on their differential expression within the olfactory organs and presence in multiple tissues, it is possible that several of these receptor types have expanded within the Echinoderm lineage. Many are likely to be species-specific with novel ligand-binding affinity and a diverse range of functions. This study is the first to describe the presence of variant Ionotropic Glutamate Receptors in any Echinoderm, and is only the second study to investigate chemosensory receptors in any starfish or marine pest. These results represent a significant step forward in understanding the chemosensory abilities of COTS.}, } @article {pmid30497380, year = {2018}, author = {Zamora-Lagos, MA and Eckstein, S and Langer, A and Gazanis, A and Pfeiffer, F and Habermann, B and Heermann, R}, title = {Phenotypic and genomic comparison of Photorhabdus luminescens subsp. laumondii TT01 and a widely used rifampicin-resistant Photorhabdus luminescens laboratory strain.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {854}, pmid = {30497380}, issn = {1471-2164}, support = {HE5247/5-2//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND: Photorhabdus luminescens is an enteric bacterium, which lives in mutualistic association with soil nematodes and is highly pathogenic for a broad spectrum of insects. A complete genome sequence for the type strain P. luminescens subsp. laumondii TT01, which was originally isolated in Trinidad and Tobago, has been described earlier. Subsequently, a rifampicin resistant P. luminescens strain has been generated with superior possibilities for experimental characterization. This strain, which is widely used in research, was described as a spontaneous rifampicin resistant mutant of TT01 and is known as TT01-RifR.

RESULTS: Unexpectedly, upon phenotypic comparison between the rifampicin resistant strain and its presumed parent TT01, major differences were found with respect to bioluminescence, pigmentation, biofilm formation, haemolysis as well as growth. Therefore, we renamed the strain TT01-RifR to DJC. To unravel the genomic basis of the observed differences, we generated a complete genome sequence for strain DJC using the PacBio long read technology. As strain DJC was supposed to be a spontaneous mutant, only few sequence differences were expected. In order to distinguish these from potential sequencing errors in the published TT01 genome, we re-sequenced a derivative of strain TT01 in parallel, also using the PacBio technology. The two TT01 genomes differed at only 30 positions. In contrast, the genome of strain DJC varied extensively from TT01, showing 13,000 point mutations, 330 frameshifts, and 220 strain-specific regions with a total length of more than 300 kb in each of the compared genomes.

CONCLUSIONS: According to the major phenotypic and genotypic differences, the rifampicin resistant P. luminescens strain, now named strain DJC, has to be considered as an independent isolate rather than a derivative of strain TT01. Strains TT01 and DJC both belong to P. luminescens subsp. laumondii.}, } @article {pmid30497378, year = {2018}, author = {Sierro, N and Battey, JND and Bovet, L and Liedschulte, V and Ouadi, S and Thomas, J and Broye, H and Laparra, H and Vuarnoz, A and Lang, G and Goepfert, S and Peitsch, MC and Ivanov, NV}, title = {The impact of genome evolution on the allotetraploid Nicotiana rustica - an intriguing story of enhanced alkaloid production.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {855}, pmid = {30497378}, issn = {1471-2164}, support = {Not applicable//Philip Morris Products S.A./ ; }, abstract = {BACKGROUND: Nicotiana rustica (Aztec tobacco), like common tobacco (Nicotiana tabacum), is an allotetraploid formed through a recent hybridization event; however, it originated from completely different progenitor species. Here, we report the comparative genome analysis of wild type N. rustica (5 Gb; 2n = 4x = 48) with its three putative diploid progenitors (2.3-3 Gb; 2n = 2x =24), Nicotiana undulata, Nicotiana paniculata and Nicotiana knightiana.

RESULTS: In total, 41% of N. rustica genome originated from the paternal donor (N. undulata), while 59% originated from the maternal donor (N. paniculata/N. knightiana). Chloroplast genome and gene analyses indicated that N. knightiana is more closely related to N. rustica than N. paniculata. Gene clustering revealed 14,623 ortholog groups common to other Nicotiana species and 207 unique to N. rustica. Genome sequence analysis indicated that N. knightiana is more closely related to N. rustica than N. paniculata, and that the higher nicotine content of N. rustica leaves is the result of the progenitor genomes combination and of a more active transport of nicotine to the shoot.

CONCLUSIONS: The availability of four new Nicotiana genome sequences provide insights into how speciation impacts plant metabolism, and in particular alkaloid transport and accumulation, and will contribute to better understanding the evolution of Nicotiana species.}, } @article {pmid30497377, year = {2018}, author = {Coyle, JF and Pagliai, FA and Zhang, D and Lorca, GL and Gonzalez, CF}, title = {Purification and partial characterization of LdtP, a cell envelope modifying enzyme in Liberibacter asiaticus.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {201}, pmid = {30497377}, issn = {1471-2180}, support = {2015-70016-23029//Agricultural Research Service/ ; 2017-03060//Agricultural Research Service/ ; }, abstract = {BACKGROUND: The aggressive spread of Liberibacter asiaticus, a bacterium closely associated with citrus greening, has given rise to an acute crisis in the citrus industry, making it imperative to expand the scientific knowledge base regarding L. asiaticus. Despite several endeavors to culture L. asiaticus, this bacterium has yet to be maintained in axenic culture, rendering identification and analysis of potential treatment targets challenging. Accordingly, a thorough understanding of biological mechanisms involved in the citrus host-microbe relationship is critical as a means of directing the search for future treatment targets. In this study, we evaluate the biochemical characteristics of CLIBASIA_01175, renamed LdtP (L,D-transpeptidase). Surrogate strains were used to evaluate its potential biological significance in gram-negative bacteria. A strain of E. coli carrying quintuple knock-outs of all genes encoding L,D-transpeptidases was utilized to demonstrate the activity of L. asiaticus LdtP.

RESULTS: This complementation study demonstrated the periplasmic localization of mature LdtP and provided evidence for the biological role of LdtP in peptidoglycan modification. Further investigation highlighted the role of LdtP as a periplasmic esterase involved in modification of the lipid A moiety of the lipopolysaccharide. This work described, for the first time, an enzyme of the L,D-transpeptidase family with moonlighting enzyme activity directed to the modification of the bacterial cell wall and LPS.

CONCLUSIONS: Taken together, the data indicates that LdtP is a novel protein involved in an alternative pathway for modification of the bacterial cell, potentially affording L. asiaticus a means to survive within the host.}, } @article {pmid30497376, year = {2018}, author = {Schaafsma, GCP and Vihinen, M}, title = {Representativeness of variation benchmark datasets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {461}, pmid = {30497376}, issn = {1471-2105}, support = {2015-02510//Vetenskapsrådet/ ; }, mesh = {*Benchmarking ; Chromosomes/genetics ; *Databases as Topic ; Databases, Protein ; Gene Frequency ; Gene Ontology ; Genetic Variation ; Humans ; Molecular Sequence Annotation ; Protein Domains ; Proteins/chemistry ; }, abstract = {BACKGROUND: Benchmark datasets are essential for both method development and performance assessment. These datasets have numerous requirements, representativeness being one. In the case of variant tolerance/pathogenicity prediction, representativeness means that the dataset covers the space of variations and their effects.

RESULTS: We performed the first analysis of the representativeness of variation benchmark datasets. We used statistical approaches to investigate how proteins in the benchmark datasets were representative for the entire human protein universe. We investigated the distributions of variants in chromosomes, protein structures, CATH domains and classes, Pfam protein families, Enzyme Commission (EC) classifications and Gene Ontology annotations in 24 datasets that have been used for training and testing variant tolerance prediction methods. All the datasets were available in VariBench or VariSNP databases. We tested also whether the pathogenic variant datasets contained neutral variants defined as those that have high minor allele frequency in the ExAC database. The distributions of variants over the chromosomes and proteins varied greatly between the datasets.

CONCLUSIONS: None of the datasets was found to be well representative. Many of the tested datasets had quite good coverage of the different protein characteristics. Dataset size correlates to representativeness but only weakly to the performance of methods trained on them. The results imply that dataset representativeness is an important factor and should be taken into account in predictor development and testing.}, } @article {pmid30497375, year = {2018}, author = {Molina, D and Cossio-Pérez, R and Rocha-Roa, C and Pedraza, L and Cortes, E and Hernández, A and Gómez-Marín, JE}, title = {Protein targets of thiazolidinone derivatives in Toxoplasma gondii and insights into their binding to ROP18.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {856}, pmid = {30497375}, issn = {1471-2164}, support = {111377757104//colciencias/ ; }, abstract = {BACKGROUND: Thiazolidinone derivatives show inhibitory activity (IC50) against the Toxoplasma gondii parasite, as well as high selectivity with high therapeutic index. To disclose the target proteins of the thiazolidinone core in this parasite, we explored in silico the active sites of different T. gondii proteins and estimated the binding-free energy of reported thiazolidinone molecules with inhibitory effect on invasion and replication of the parasite inside host cells. This enabled us to describe some of the most suitable structural characteristics to design a compound derived from the thiazolidinone core.

RESULTS: The best binding affinity was observed in the active site of kinase proteins, we selected the active site of the T. gondii ROP18 kinase, because it is an important factor for the virulence and survival of the parasite. We present the possible effect of a derivative of thiazolidinone core in the active site of T. gondii ROP18 and described some characteristics of substituent groups that could improve the affinity and specificity of compounds derived from the thiazolidinone core against T. gondii.

CONCLUSIONS: The results of our study suggest that compounds derived from the thiazolidinone core have a preference for protein kinases of T. gondii, being promising compounds for the development of new drugs with potential anti-toxoplasmosis activity. Our findings highlight the importance of use computational studies for the understanding of the action mechanism of compounds with biological activity.}, } @article {pmid30497374, year = {2018}, author = {Stachowiak, M and Szczerbal, I and Flisikowski, K}, title = {Investigation of allele-specific expression of genes involved in adipogenesis and lipid metabolism suggests complex regulatory mechanisms of PPARGC1A expression in porcine fat tissues.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {107}, pmid = {30497374}, issn = {1471-2156}, abstract = {BACKGROUND: The expression of genes involved in regulating adipogenesis and lipid metabolism may affect economically important fatness traits in pigs. Allele-specific expression (ASE) reflects imbalance between allelic transcript levels and can be used to identify underlying cis-regulatory elements. ASE has not yet been intensively studied in pigs. The aim of this investigation was to analyze the differential allelic expression of four genes, PPARA, PPARG, SREBF1, and PPARGC1A, which are involved in the regulation of fat deposition in porcine subcutaneous and visceral fat and longissimus dorsi muscle.

RESULTS: Quantification of allelic proportions by pyrosequencing revealed that both alleles of PPARG and SREBF1 are expressed at similar levels. PPARGC1A showed the greatest ASE imbalance in fat deposits in Polish Large White (PLW), Polish Landrace and Pietrain pigs; and PPARA in PLW pigs. Significant deviations of mean PPARGC1A allelic transcript ratio between cDNA and genomic DNA were detected in all tissues, with the most pronounced difference (p < 0.001) in visceral fat of PLW pigs. To search for potential cis-regulatory elements affecting ASE in the PPARGC1A gene we analyzed the effects of four SNPs (rs337351686, rs340650517, rs336405906 and rs345224049) in the promoter region, but none were associated with ASE in the breeds studied. DNA methylation analysis revealed significant CpG methylation differences between samples showing balanced (allelic transcript ratio ≈1) and imbalanced allelic expression for CpG site at the genomic position in chromosome 8 (SSC8): 18527678 in visceral fat (p = 0.017) and two CpG sites (SSC8:18525215, p = 0.030; SSC8:18525237, p = 0.031) in subcutaneous fat.

CONCLUSIONS: Our analysis of differential allelic expression suggests that PPARGC1A is subjected to cis-regulation in porcine fat tissues. Further studies are necessary to identify other regulatory elements localized outside the PPARGC1A proximal promoter region.}, } @article {pmid30497373, year = {2018}, author = {Roach, MJ and Schmidt, SA and Borneman, AR}, title = {Purge Haplotigs: allelic contig reassignment for third-gen diploid genome assemblies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {460}, pmid = {30497373}, issn = {1471-2105}, mesh = {*Alleles ; Arabidopsis/genetics ; *Contig Mapping ; *Diploidy ; Genome, Plant ; Haploidy ; Haplotypes/*genetics ; Heterozygote ; High-Throughput Nucleotide Sequencing/*methods ; Homozygote ; Polymorphism, Single Nucleotide/genetics ; Software ; }, abstract = {BACKGROUND: Recent developments in third-gen long read sequencing and diploid-aware assemblers have resulted in the rapid release of numerous reference-quality assemblies for diploid genomes. However, assembly of highly heterozygous genomes is still problematic when regional heterogeneity is so high that haplotype homology is not recognised during assembly. This results in regional duplication rather than consolidation into allelic variants and can cause issues with downstream analysis, for example variant discovery, or haplotype reconstruction using the diploid assembly with unpaired allelic contigs.

RESULTS: A new pipeline-Purge Haplotigs-was developed specifically for third-gen sequencing-based assemblies to automate the reassignment of allelic contigs, and to assist in the manual curation of genome assemblies. The pipeline uses a draft haplotype-fused assembly or a diploid assembly, read alignments, and repeat annotations to identify allelic variants in the primary assembly. The pipeline was tested on a simulated dataset and on four recent diploid (phased) de novo assemblies from third-generation long-read sequencing, and compared with a similar tool. After processing with Purge Haplotigs, haploid assemblies were less duplicated with minimal impact on genome completeness, and diploid assemblies had more pairings of allelic contigs.

CONCLUSIONS: Purge Haplotigs improves the haploid and diploid representations of third-gen sequencing based genome assemblies by identifying and reassigning allelic contigs. The implementation is fast and scales well with large genomes, and it is less likely to over-purge repetitive or paralogous elements compared to alignment-only based methods. The software is available at https://bitbucket.org/mroachawri/purge_haplotigs under a permissive MIT licence.}, } @article {pmid30497372, year = {2018}, author = {Yang, R and Watson, D and Williams, J and Kumar, R and Campbell, R and Mudunuri, U and Hammamieh, R and Jett, M}, title = {PanoromiX: a time-course network medicine platform integrating molecular assays and pathophenotypic data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {458}, pmid = {30497372}, issn = {1471-2105}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; 09284002//Medical Research and Materiel Command/ ; }, mesh = {Biological Assay/*methods ; Gene Regulatory Networks ; Phenotype ; Prions/metabolism ; *Software ; Time Factors ; }, abstract = {BACKGROUND: Network medicine aims to map molecular perturbations of any given diseases onto complex networks with functional interdependencies that underlie a pathological phenotype. Furthermore, investigating the time dimension of disease progression from a network perspective is key to gaining key insights to the disease process and to identify diagnostic or therapeutic targets. Existing platforms are ineffective to modularize the large complex systems into subgroups and consolidate heterogeneous data to web-based interactive animation.

RESULTS: We have developed PanoromiX platform, a data-agnostic dynamic interactive visualization web application, enables the visualization of outputs from genome based molecular assays onto modular and interactive networks that are correlated with any pathophenotypic data (MRI, Xray, behavioral, etc.) over a time course all in one pane. As a result, PanoromiX reveals the complex organizing principles that orchestrate a disease-pathology from a gene regulatory network (nodes, edges, hubs, etc.) perspective instead of snap shots of assays. Without extensive programming experience, users can design, share, and interpret their dynamic networks through the PanoromiX platform with rich built-in functionalities.

CONCLUSIONS: This emergent tool of network medicine is the first to visualize the interconnectedness of tailored genome assays to pathological networks and phenotypes for cells or organisms in a data-agnostic manner. As an advanced network medicine tool, PanoromiX allows monitoring of panel of biomarker perturbations over the progression of diseases, disease classification based on changing network modules that corresponds to specific patho-phenotype as opposed to clinical symptoms, systematic exploration of complex molecular interactions and distinct disease states via regulatory network changes, and the discovery of novel diagnostic and therapeutic targets.}, } @article {pmid30497371, year = {2018}, author = {Guinot, F and Szafranski, M and Ambroise, C and Samson, F}, title = {Learning the optimal scale for GWAS through hierarchical SNP aggregation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {459}, pmid = {30497371}, issn = {1471-2105}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Algorithms ; Area Under Curve ; Case-Control Studies ; Computer Simulation ; Gene Frequency/genetics ; *Genome-Wide Association Study ; Humans ; Linkage Disequilibrium/genetics ; Numerical Analysis, Computer-Assisted ; Phenotype ; Polymorphism, Single Nucleotide/*genetics ; ROC Curve ; Spondylitis, Ankylosing/genetics ; }, abstract = {BACKGROUND: Genome-Wide Association Studies (GWAS) seek to identify causal genomic variants associated with rare human diseases. The classical statistical approach for detecting these variants is based on univariate hypothesis testing, with healthy individuals being tested against affected individuals at each locus. Given that an individual's genotype is characterized by up to one million SNPs, this approach lacks precision, since it may yield a large number of false positives that can lead to erroneous conclusions about genetic associations with the disease. One way to improve the detection of true genetic associations is to reduce the number of hypotheses to be tested by grouping SNPs.

RESULTS: We propose a dimension-reduction approach which can be applied in the context of GWAS by making use of the haplotype structure of the human genome. We compare our method with standard univariate and group-based approaches on both synthetic and real GWAS data.

CONCLUSION: We show that reducing the dimension of the predictor matrix by aggregating SNPs gives a greater precision in the detection of associations between the phenotype and genomic regions.}, } @article {pmid30497370, year = {2018}, author = {Xiao, H and Bartoszek, K and Lio', P}, title = {Multi-omic analysis of signalling factors in inflammatory comorbidities.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {439}, pmid = {30497370}, issn = {1471-2105}, mesh = {*Comorbidity ; DNA Methylation/genetics ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Regulatory Networks ; Genetic Association Studies ; Genomics/*methods ; Humans ; Inflammation/*genetics/*pathology ; Multigene Family ; Phylogeny ; Principal Component Analysis ; Receptors, Tumor Necrosis Factor/genetics ; *Signal Transduction ; }, abstract = {BACKGROUND: Inflammation is a core element of many different, systemic and chronic diseases that usually involve an important autoimmune component. The clinical phase of inflammatory diseases is often the culmination of a long series of pathologic events that started years before. The systemic characteristics and related mechanisms could be investigated through the multi-omic comparative analysis of many inflammatory diseases. Therefore, it is important to use molecular data to study the genesis of the diseases. Here we propose a new methodology to study the relationships between inflammatory diseases and signalling molecules whose dysregulation at molecular levels could lead to systemic pathological events observed in inflammatory diseases.

RESULTS: We first perform an exploratory analysis of gene expression data of a number of diseases that involve a strong inflammatory component. The comparison of gene expression between disease and healthy samples reveals the importance of members of gene families coding for signalling factors. Next, we focus on interested signalling gene families and a subset of inflammation related diseases with multi-omic features including both gene expression and DNA methylation. We introduce a phylogenetic-based multi-omic method to study the relationships between multi-omic features of inflammation related diseases by integrating gene expression, DNA methylation through sequence based phylogeny of the signalling gene families. The models of adaptations between gene expression and DNA methylation can be inferred from pre-estimated evolutionary relationship of a gene family. Members of the gene family whose expression or methylation levels significantly deviate from the model are considered as the potential disease associated genes.

CONCLUSIONS: Applying the methodology to four gene families (the chemokine receptor family, the TNF receptor family, the TGF- β gene family, the IL-17 gene family) in nine inflammation related diseases, we identify disease associated genes which exhibit significant dysregulation in gene expression or DNA methylation in the inflammation related diseases, which provides clues for functional associations between the diseases.}, } @article {pmid30497369, year = {2018}, author = {Fiscon, G and Conte, F and Paci, P}, title = {SWIM tool application to expression data of glioblastoma stem-like cell lines, corresponding primary tumors and conventional glioma cell lines.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {436}, pmid = {30497369}, issn = {1471-2105}, mesh = {Adult ; Brain Neoplasms/genetics ; Cell Line, Tumor ; Cluster Analysis ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Genes, Neoplasm ; Genes, Switch ; Glioblastoma/*genetics/*pathology ; Glioma/*genetics/*pathology ; Humans ; MicroRNAs/genetics/metabolism ; Neoplastic Stem Cells/*metabolism/pathology ; *Software ; Survival Analysis ; Up-Regulation ; }, abstract = {BACKGROUND: It is well-known that glioblastoma contains self-renewing, stem-like subpopulation with the ability to sustain tumor growth. These cells - called cancer stem-like cells - share certain phenotypic characteristics with untransformed stem cells and are resistant to many conventional cancer therapies, which might explain the limitations in curing human malignancies. Thus, the identification of genes controlling the differentiation of these stem-like cells is becoming a successful therapeutic strategy, owing to the promise of novel targets for treating malignancies.

METHODS: Recently, we developed SWIM, a software able to unveil a small pool of genes - called switch genes - critically associated with drastic changes in cell phenotype. Here, we applied SWIM to the expression profiling of glioblastoma stem-like cells and conventional glioma cell lines, in order to identify switch genes related to stem-like phenotype.

RESULTS: SWIM identifies 171 switch genes that are all down-regulated in glioblastoma stem-like cells. This list encompasses genes like CAV1, COL5A1, COL6A3, FLNB, HMMR, ITGA3, ITGA5, MET, SDC1, THBS1, and VEGFC, involved in "ECM-receptor interaction" and "focal adhesion" pathways. The inhibition of switch genes highly correlates with the activation of genes related to neural development and differentiation, such as the 4-core OLIG2, POU3F2, SALL2, SOX2, whose induction has been shown to be sufficient to reprogram differentiated glioblastoma into stem-like cells. Among switch genes, the transcription factor FOSL1 appears as the brightest star since: it is down-regulated in stem-like cells; it highly negatively correlates with the 4-core genes that are all up-regulated in stem-like cells; the promoter regions of the 4-core genes harbor a consensus binding motif for FOSL1.

CONCLUSIONS: We suggest that the inhibition of switch genes in stem-like cells could induce the deregulation of cell communication pathways, contributing to neoplastic progression and tumor invasiveness. Conversely, their activation could restore the physiological equilibrium between cell adhesion and migration, hampering the progression of cancer. Moreover, we posit FOSL1 as promising candidate to orchestrate the differentiation of cancer stem-like cells by repressing the 4-core genes' expression, which severely halts cancer growth and might affect the therapeutic outcome. We suggest FOSL1 as novel putative therapeutic and prognostic biomarker, worthy of further investigation.}, } @article {pmid30497368, year = {2018}, author = {Elez, K and Bonvin, AMJJ and Vangone, A}, title = {Distinguishing crystallographic from biological interfaces in protein complexes: role of intermolecular contacts and energetics for classification.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {438}, pmid = {30497368}, issn = {1471-2105}, mesh = {Algorithms ; Crystallography, X-Ray ; Databases, Protein ; *Energy Metabolism ; Machine Learning ; Proteins/*chemistry ; Reproducibility of Results ; Static Electricity ; }, abstract = {BACKGROUND: Study of macromolecular assemblies is fundamental to understand functions in cells. X-ray crystallography is the most common technique to solve their 3D structure at atomic resolution. In a crystal, however, both biologically-relevant interfaces and non-specific interfaces resulting from crystallographic packing are observed. Due to the complexity of the biological assemblies currently tackled, classifying those interfaces, i.e. distinguishing biological from crystal lattice interfaces, is not trivial and often prone to errors. In this context, analyzing the physico-chemical characteristics of biological/crystal interfaces can help researchers identify possible features that distinguish them and gain a better understanding of the systems.

RESULTS: In this work, we are providing new insights into the differences between biological and crystallographic complexes by focusing on "pair-properties" of interfaces that have not yet been fully investigated. We investigated properties such intermolecular residue-residue contacts (already successfully applied to the prediction of binding affinities) and interaction energies (electrostatic, Van der Waals and desolvation). By using the XtalMany and BioMany interface datasets, we show that interfacial residue contacts, classified as a function of their physico-chemical properties, can distinguish between biological and crystallographic interfaces. The energetic terms show, on average, higher values for crystal interfaces, reflecting a less stable interface due to crystal packing compared to biological interfaces. By using a variety of machine learning approaches, we trained a new interface classification predictor based on contacts and interaction energetic features. Our predictor reaches an accuracy in classifying biological vs crystal interfaces of 0.92, compared to 0.88 for EPPIC (one of the main state-of-the-art classifiers reporting same performance as PISA).

CONCLUSION: In this work we have gained insights into the nature of intermolecular contacts and energetics terms distinguishing biological from crystallographic interfaces. Our findings might have a broader applicability in structural biology, for example for the identification of near native poses in docking. We implemented our classification approach into an easy-to-use and fast software, freely available to the scientific community from http://github.com/haddocking/interface-classifier .}, } @article {pmid30497367, year = {2018}, author = {Ambrosino, L and Ruggieri, V and Bostan, H and Miralto, M and Vitulo, N and Zouine, M and Barone, A and Bouzayen, M and Frusciante, L and Pezzotti, M and Valle, G and Chiusano, ML}, title = {Multilevel comparative bioinformatics to investigate evolutionary relationships and specificities in gene annotations: an example for tomato and grapevine.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {435}, pmid = {30497367}, issn = {1471-2105}, mesh = {*Biological Evolution ; Computational Biology/*methods ; Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Genome, Plant ; Lycopersicon esculentum/*genetics ; *Molecular Sequence Annotation ; *Multilevel Analysis ; Phylogeny ; RNA, Messenger/genetics/metabolism ; Transcription Factors/metabolism ; Vitis/*genetics ; }, abstract = {BACKGROUND: "Omics" approaches may provide useful information for a deeper understanding of speciation events, diversification and function innovation. This can be achieved by investigating the molecular similarities at sequence level between species, allowing the definition of ortholog and paralog genes. However, the spreading of sequenced genome, often endowed with still preliminary annotations, requires suitable bioinformatics to be appropriately exploited in this framework.

RESULTS: We presented here a multilevel comparative approach to investigate on genome evolutionary relationships and peculiarities of two fleshy fruit species of relevant agronomic interest, Solanum lycopersicum (tomato) and Vitis vinifera (grapevine). We defined 17,823 orthology relationships between tomato and grapevine reference gene annotations. The resulting orthologs are associated with the detected paralogs in each species, permitting the definition of gene networks, useful to investigate the different relationships. The reconciliation of the compared collections in terms of an updating of the functional descriptions was also exploited. All the results were made accessible in ComParaLogs, a dedicated bioinformatics platform available at http://biosrv.cab.unina.it/comparalogs/gene/search .

CONCLUSIONS: The aim of the work was to suggest a reliable approach to detect all similarities of gene loci between two species based on the integration of results from different levels of information, such as the gene, the transcript and the protein sequences, overcoming possible limits due to exclusive protein versus protein comparisons. This to define reliable ortholog and paralog genes, as well as species specific gene loci in the two species, overcoming limits due to the possible draft nature of preliminary gene annotations. Moreover, reconciled functional descriptions, as well as common or peculiar enzymatic classes and protein domains from tomato and grapevine, together with the definition of species-specific gene sets after the pairwise comparisons, contributed a comprehensive set of information useful to comparatively exploit the two species gene annotations and investigate on differences between species with climacteric and non-climacteric fruits. In addition, the definition of networks of ortholog genes and of associated paralogs, and the organization of web-based interfaces for the exploration of the results, defined a friendly computational bench-work in support of comparative analyses between two species.}, } @article {pmid30497365, year = {2018}, author = {Hu, R and Xiao, J and Gu, T and Yu, X and Zhang, Y and Chang, J and Yang, G and He, G}, title = {Correction to: Genome-wide identification and analysis of WD40 proteins in wheat (Triticum aestivum L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {852}, pmid = {30497365}, issn = {1471-2164}, abstract = {Following the publication of this article [1], the authors reported the following errors.}, } @article {pmid30497364, year = {2018}, author = {Girotto, S and Comin, M and Pizzi, C}, title = {Efficient computation of spaced seed hashing with block indexing.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {441}, pmid = {30497364}, issn = {1471-2105}, mesh = {*Algorithms ; Base Sequence ; Computational Biology/*methods ; Metagenomics ; Time Factors ; }, abstract = {BACKGROUND: Spaced-seeds, i.e. patterns in which some fixed positions are allowed to be wild-cards, play a crucial role in several bioinformatics applications involving substrings counting and indexing, by often providing better sensitivity with respect to k-mers based approaches. K-mers based approaches are usually fast, being based on efficient hashing and indexing that exploits the large overlap between consecutive k-mers. Spaced-seeds hashing is not as straightforward, and it is usually computed from scratch for each position in the input sequence. Recently, the FSH (Fast Spaced seed Hashing) approach was proposed to improve the time required for computation of the spaced seed hashing of DNA sequences with a speed-up of about 1.5 with respect to standard hashing computation.

RESULTS: In this work we propose a novel algorithm, Fast Indexing for Spaced seed Hashing (FISH), based on the indexing of small blocks that can be combined to obtain the hashing of spaced-seeds of any length. The method exploits the fast computation of the hashing of runs of consecutive 1 in the spaced seeds, that basically correspond to k-mer of the length of the run.

CONCLUSIONS: We run several experiments, on NGS data from simulated and synthetic metagenomic experiments, to assess the time required for the computation of the hashing for each position in each read with respect to several spaced seeds. In our experiments, FISH can compute the hashing values of spaced seeds with a speedup, with respect to the traditional approach, between 1.9x to 6.03x, depending on the structure of the spaced seeds.}, } @article {pmid30497363, year = {2018}, author = {Sperlea, T and Füser, S and Boenigk, J and Heider, D}, title = {SEDE-GPS: socio-economic data enrichment based on GPS information.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {440}, pmid = {30497363}, issn = {1471-2105}, mesh = {Algorithms ; Biodiversity ; *Geographic Information Systems ; Lakes ; Machine Learning ; Microbiota ; Socioeconomic Factors ; }, abstract = {BACKGROUND: Microbes are essentail components of all ecosystems because they drive many biochemical processes and act as primary producers. In freshwater ecosystems, the biodiversity in and the composition of microbial communities can be used as indicators for environmental quality. Recently, some environmental features have been identified that influence microbial ecosystems. However, the impact of human action on lake microbiomes is not well understood. This is, in part, due to the fact that environmental data is, albeit theoretically accessible, not easily available.

RESULTS: In this work, we present SEDE-GPS, a tool that gathers data that are relevant to the environment of an user-provided GPS coordinate. To this end, it accesses a list of public and corporate databases and aggregates the information in a single file, which can be used for further analysis. To showcase the use of SEDE-GPS, we enriched a lake microbial ecology sequencing dataset with around 18,000 socio-economic, climate, and geographic features. The sources of SEDE-GPS are public databases such as Eurostat, the Climate Data Center, and OpenStreetMap, as well as corporate sources such as Twitter. Using machine learning and feature selection methods, we were able to identify features in the data provided by SEDE-GPS that can be used to predict lake microbiome alpha diversity.

CONCLUSION: The results presented in this study show that SEDE-GPS is a handy and easy-to-use tool for comprehensive data enrichment for studies of ecology and other processes that are affected by environmental features. Furthermore, we present lists of environmental, socio-economic, and climate features that are predictive for microbial biodiversity in lake ecosystems. These lists indicate that human action has a major impact on lake microbiomes. SEDE-GPS and its source code is available for download at http://SEDE-GPS.heiderlab.de.}, } @article {pmid30497362, year = {2018}, author = {Tangherlini, M and Miralto, M and Colantuono, C and Sangiovanni, M and Dell' Anno, A and Corinaldesi, C and Danovaro, R and Chiusano, ML}, title = {GLOSSary: the GLobal Ocean 16S subunit web accessible resource.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {443}, pmid = {30497362}, issn = {1471-2105}, mesh = {Computational Biology/*methods ; Geography ; *Internet ; Metagenomics/methods ; *Oceans and Seas ; RNA, Ribosomal, 16S/*genetics ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: Environmental metagenomics is a challenging approach that is exponentially spreading in the scientific community to investigate taxonomic diversity and possible functions of the biological components. The massive amount of sequence data produced, often endowed with rich environmental metadata, needs suitable computational tools to fully explore the embedded information. Bioinformatics plays a key role in providing methodologies to manage, process and mine molecular data, integrated with environmental metagenomics collections. One such relevant example is represented by the Tara Ocean Project.

RESULTS: We considered the Tara 16S miTAGs released by the consortium, representing raw sequences from a shotgun metagenomics approach with similarities to 16S rRNA genes. We generated assembled 16S rDNA sequences, which were classified according to their lengths, the possible presence of chimeric reads, the putative taxonomic affiliation. The dataset was included in GLOSSary (the GLobal Ocean 16S Subunit web accessible resource), a bioinformatics platform to organize environmental metagenomics data. The aims of this work were: i) to present alternative computational approaches to manage challenging metagenomics data; ii) to set up user friendly web-based platforms to allow the integration of environmental metagenomics sequences and of the associated metadata; iii) to implement an appropriate bioinformatics platform supporting the analysis of 16S rDNA sequences exploiting reference datasets, such as the SILVA database. We organized the data in a next-generation NoSQL "schema-less" database, allowing flexible organization of large amounts of data and supporting native geospatial queries. A web interface was developed to permit an interactive exploration and a visual geographical localization of the data, either raw miTAG reads or 16S contigs, from our processing pipeline. Information on unassembled sequences is also available. The taxonomic affiliations of contigs and miTAGs, and the spatial distribution of the sampling sites and their associated sequence libraries, as they are contained in the Tara metadata, can be explored by a query interface, which allows both textual and visual investigations. In addition, all the sequence data were made available for a dedicated BLAST-based web application alongside the SILVA collection.

CONCLUSIONS: GLOSSary provides an expandable bioinformatics environment, able to support the scientific community in current and forthcoming environmental metagenomics analyses.}, } @article {pmid30497361, year = {2018}, author = {Fiannaca, A and La Rosa, M and La Paglia, L and Urso, A}, title = {miRTissue: a web application for the analysis of miRNA-target interactions in human tissues.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {434}, pmid = {30497361}, issn = {1471-2105}, mesh = {Biomarkers, Tumor/metabolism ; Computational Biology/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; *Internet ; MicroRNAs/*genetics/metabolism ; Neoplasms/genetics ; Organ Specificity/*genetics ; Protein Interaction Maps/genetics ; *Software ; }, abstract = {BACKGROUND: microRNAs act as regulators of gene expression interacting with their gene targets. Current bioinformatics services, such as databases of validated miRNA-target interactions and prediction tools, usually provide interactions without any information about what tissue that interaction is more likely to appear nor information about the type of interactions, causing mRNA degradation or translation inhibition respectively.

RESULTS: In this work, we introduce miRTissue, a web application that combines validated miRNA-target interactions with statistical correlation among expression profiles of miRNAs, genes and proteins in 15 different human tissues. Validated interactions are taken from the miRTarBase database, while expression profiles are downloaded from The Cancer Genome Atlas repository. As a result, the service provides a tissue-specific characterisation of each couple of miRNA and gene together with its statistical significance (p-value). The inclusion of protein data also allows providing the type of interaction. Moreover, miRTissue offers several views for analysing interactions, focusing for example on the comparison between different cancer types or different tissue conditions. All the results are freely downloadable in the most common formats.

CONCLUSIONS: miRTissue fills a gap concerning current bioinformatics services related to miRNA-target interactions because it provides a tissue-specific context to each validated interaction and the type of interaction itself. miRTissue is easily browsable allowing the user to select miRNAs, genes, cancer types and tissue conditions. The results can be sorted according to p-values to immediately identify those interactions that are more likely to occur in a given tissue. miRTissue is available at http://tblab.pa.icar.cnr.it/mirtissue.html.}, } @article {pmid30497360, year = {2018}, author = {Cimmaruta, C and Citro, V and Andreotti, G and Liguori, L and Cubellis, MV and Hay Mele, B}, title = {Challenging popular tools for the annotation of genetic variations with a real case, pathogenic mutations of lysosomal alpha-galactosidase.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {433}, pmid = {30497360}, issn = {1471-2105}, mesh = {Fabry Disease/enzymology/genetics ; Humans ; Lysosomes/*enzymology ; Molecular Sequence Annotation/*methods ; Mutation, Missense/*genetics ; Phenotype ; alpha-Galactosidase/*genetics ; }, abstract = {BACKGROUND: Severity gradation of missense mutations is a big challenge for exome annotation. Predictors of deleteriousness that are most frequently used to filter variants found by next generation sequencing, produce qualitative predictions, but also numerical scores. It has never been tested if these scores correlate with disease severity.

RESULTS: wANNOVAR, a popular tool that can generate several different types of deleteriousness-prediction scores, was tested on Fabry disease. This pathology, which is caused by a deficit of lysosomal alpha-galactosidase, has a very large genotypic and phenotypic spectrum and offers the possibility of associating a quantitative measure of the damage caused by mutations to the functioning of the enzyme in the cells. Some predictors, and in particular VEST3 and PolyPhen2 provide scores that correlate with the severity of lysosomal alpha-galactosidase mutations in a statistically significant way.

CONCLUSIONS: Sorting disease mutations by severity is possible and offers advantages over binary classification. Dataset for testing and training in silico predictors can be obtained by transient transfection and evaluation of residual activity of mutants in cell extracts. This approach consents to quantitative data for severe, mild and non pathological variants.}, } @article {pmid30497359, year = {2018}, author = {Mancini, A and Eyassu, F and Conway, M and Occhipinti, A and Liò, P and Angione, C and Pucciarelli, S}, title = {CiliateGEM: an open-project and a tool for predictions of ciliate metabolic variations and experimental condition design.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {442}, pmid = {30497359}, issn = {1471-2105}, mesh = {Animals ; Biomass ; Phylogeny ; *Research Design ; *Software ; Tetrahymena thermophila/growth & development/*metabolism ; }, abstract = {BACKGROUND: The study of cell metabolism is becoming central in several fields such as biotechnology, evolution/adaptation and human disease investigations. Here we present CiliateGEM, the first metabolic network reconstruction draft of the freshwater ciliate Tetrahymena thermophila. We also provide the tools and resources to simulate different growth conditions and to predict metabolic variations. CiliateGEM can be extended to other ciliates in order to set up a meta-model, i.e. a metabolic network reconstruction valid for all ciliates. Ciliates are complex unicellular eukaryotes of presumably monophyletic origin, with a phylogenetic position that is equal from plants and animals. These cells represent a new concept of unicellular system with a high degree of species, population biodiversity and cell complexity. Ciliates perform in a single cell all the functions of a pluricellular organism, including locomotion, feeding, digestion, and sexual processes.

RESULTS: After generating the model, we performed an in-silico simulation with the presence and absence of glucose. The lack of this nutrient caused a 32.1% reduction rate in biomass synthesis. Despite the glucose starvation, the growth did not stop due to the use of alternative carbon sources such as amino acids.

CONCLUSIONS: The future models obtained from CiliateGEM may represent a new approach to describe the metabolism of ciliates. This tool will be a useful resource for the ciliate research community in order to extend these species as model organisms in different research fields. An improved understanding of ciliate metabolism could be relevant to elucidate the basis of biological phenomena like genotype-phenotype relationships, population genetics, and cilia-related disease mechanisms.}, } @article {pmid30497358, year = {2018}, author = {Bonnici, V and Giugno, R and Manca, V}, title = {PanDelos: a dictionary-based method for pan-genome content discovery.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 15}, pages = {437}, pmid = {30497358}, issn = {1471-2105}, mesh = {Bacteria/genetics ; Databases, Genetic ; *Dictionaries as Topic ; Gene Duplication ; *Genome, Bacterial ; Phylogeny ; *Software ; Time Factors ; }, abstract = {BACKGROUND: Pan-genome approaches afford the discovery of homology relations in a set of genomes, by determining how some gene families are distributed among a given set of genomes. The retrieval of a complete gene distribution among a class of genomes is an NP-hard problem because computational costs increase with the number of analyzed genomes, in fact, all-against-all gene comparisons are required to completely solve the problem. In presence of phylogenetically distant genomes, due to the variability introduced in gene duplication and transmission, the task of recognizing homologous genes becomes even more difficult. A challenge on this field is that of designing fast and adaptive similarity measures in order to find a suitable pan-genome structure of homology relations.

RESULTS: We present PanDelos, a stand alone tool for the discovery of pan-genome contents among phylogenetic distant genomes. The methodology is based on information theory and network analysis. It is parameter-free because thresholds are automatically deduced from the context. PanDelos avoids sequence alignment by introducing a measure based on k-mer multiplicity. The k-mer length is defined according to general arguments rather than empirical considerations. Homology candidate relations are integrated into a global network and groups of homologous genes are extracted by applying a community detection algorithm.

CONCLUSIONS: PanDelos outperforms existing approaches, Roary and EDGAR, in terms of running times and quality content discovery. Tests were run on collections of real genomes, previously used in analogous studies, and in synthetic benchmarks that represent fully trusted golden truth. The software is available at https://github.com/GiugnoLab/PanDelos .}, } @article {pmid30497296, year = {2018}, author = {Reed, LI and Stratton, R and Rambeas, JD}, title = {Face Value and Cheap Talk: How Smiles Can Increase or Decrease the Credibility of Our Words.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918814400}, doi = {10.1177/1474704918814400}, pmid = {30497296}, issn = {1474-7049}, abstract = {How do our facial expressions affect the credibility of our words? We test whether smiles, either uninhibited or inhibited, affect the credibility of a written statement. Participants viewed a confederate partner displaying a neutral expression, non-Duchenne smile, Duchenne smile, or controlled smile, paired with a written statement. Participants then made a behavioral decision based on how credible they perceived the confederate's statement to be. Compared to a neutral expression, Experiment 1 found that participants were more likely to believe the confederate's statement when it was paired with a deliberate Duchenne smile and less likely to believe the confederate's statement when it was paired with a deliberate controlled smile. Experiment 2 replicated these findings with spontaneously emitted expressions. These findings provide evidence that uninhibited facial expressions can increase the credibility accompanying statements, while inhibited ones can decrease credibility.}, } @article {pmid30497074, year = {2018}, author = {}, title = {Contents Vol. 12, 2018.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {6}, pages = {}, doi = {10.1159/000495227}, pmid = {30497074}, issn = {1661-5433}, } @article {pmid30496844, year = {2019}, author = {Boubli, JP and Byrne, H and da Silva, MNF and Silva-Júnior, J and Costa Araújo, R and Bertuol, F and Gonçalves, J and de Melo, FR and Rylands, AB and Mittermeier, RA and Silva, FE and Nash, SD and Canale, G and Alencar, RM and Rossi, RV and Carneiro, J and Sampaio, I and Farias, IP and Schneider, H and Hrbek, T}, title = {On a new species of titi monkey (Primates: Plecturocebus Byrne et al., 2016), from Alta Floresta, southern Amazon, Brazil.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {117-137}, doi = {10.1016/j.ympev.2018.11.012}, pmid = {30496844}, issn = {1095-9513}, abstract = {The taxonomy of the titi monkeys (Callicebinae) has recently received considerable attention. It is now recognised that this subfamily is composed of three genera with 33 species, seven of them described since 2002. Here, we describe a new species of titi, Plecturocebus, from the municipality of Alta Floresta, Mato Grosso, Brazil. We adopt an integrative taxonomic approach that includes phylogenomic analyses, pelage characters, and locality records. A reduced representation genome-wide approach was employed to assess phylogenetic relationships among species of the eastern Amazonian clade of the Plecturocebus moloch group. Using existing records, we calculated the Extent of Occurrence (EOO) of the new species and estimated future habitat loss for the region based on predictive models. We then evaluated the species' conservation status using the IUCN Red list categories and criteria. The new species presents a unique combination of morphological characters: (1) grey agouti colouration on the crown and dorsal parts; (2) entirely bright red-brown venter; (3) an almost entirely black tail with a pale tip; and (4) light yellow colouration of the hair on the cheeks contrasting with bright red-brown hair on the sides of the face. Our phylogenetic reconstructions based on maximum-likelihood and Bayesian methods revealed well-supported species relationships, with the Alta Floresta taxon as sister to P. moloch + P. vieirai. The species EOO is 10,166,653 ha and we predict a total habitat loss of 86% of its original forest habitat under a "business as usual" scenario in the next 24 years, making the newly discovered titi monkey a Critically Endangered species under the IUCN A3c criterion. We give the new titi monkey a specific epithet based on: (1) clear monophyly of this lineage revealed by robust genomic and mitochondrial data; (2) distinct and diagnosable pelage morphology; and (3) a well-defined geographical distribution with clear separation from other closely related taxa. Urgent conservation measures are needed to safeguard the future of this newly discovered and already critically endangered primate.}, } @article {pmid30496843, year = {2019}, author = {Jiang, CQ and Wang, GY and Xiong, J and Yang, WT and Sun, ZY and Feng, JM and Warren, A and Miao, W}, title = {Insights into the origin and evolution of Peritrichia (Oligohymenophorea, Ciliophora) based on analyses of morphology and phylogenomics.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {25-35}, doi = {10.1016/j.ympev.2018.11.018}, pmid = {30496843}, issn = {1095-9513}, abstract = {Peritrichia is a large and distinctive assemblage of ciliated protists that was first observed by Antonie van Leeuwenhoek over 340 years ago. In the last two decades the evolutionary relationships of this subclass have been increasingly debated as morphological and molecular analyses have generated contrasting conclusions. In this study, we provide genomic-scale data from 12 typical representatives. We combine taxon- and gene-rich phylogenomic analyses, with up to 151 genes (43,956 amino acid residues) from 18 freshwater, brackish and marine isolates in order to assess the systematics and evolutionary history of the Peritrichia. The main findings were: (1) the subclass Peritrichia originates from the end of the Proterozoic to the Cambrian; (2) the monophyletic Peritrichia is sister to the Peniculia (represented by Paramecium) within the class Oligohymenophorea; (3) spasmin plays a significant role in peritrich evolution: we detected the spasmin gene in target ciliates and traced the molecular evolution of spasmin, a key spasmoneme component, together with phylogenetic relationships and morphology of the peritrichs. These findings provide evidence that spasmin is an important molecule to illustrate the phylogenetic position of Peritrichia within the class Oligohymenophorea, the monophyly of Peritrichia, and the diverse and rapid evolution of sessilid peritrichs.}, } @article {pmid30496744, year = {2019}, author = {Wittig, JG and Billmeier, M and Lozano-Velasco, E and García, MR and Münsterberg, AE}, title = {Cardiac injections of AntagomiRs as a novel tool for knockdown of miRNAs during heart development.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {163-169}, doi = {10.1016/j.ydbio.2018.11.008}, pmid = {30496744}, issn = {1095-564X}, abstract = {BACKGROUND: Studying microRNA networks during heart development is essential to obtain a better understanding of developmental defects and diseases associated with the heart and to identify novel opportunities for therapeutics. Here we highlight the advantages of chicken embryos as a vertebrate model for studying intermediate processes of heart development. Avians develop a four-chambered heart closely resembling human anatomy and they develop ex utero, which makes them easily accessible. Furthermore, embryos are available all year with a steady supply.

RESULTS: In this report we established a novel method for the knockdown of microRNA function by microinjecting AntagomiRs into the chicken heart in ovo. Our approach enables the targeted delivery of antagomirs into a locally restricted area and is not impacted by circulation. After further embryo development the successful miRNA knockdown was confirmed. Loss of function phenotypes can be evaluated rapidly, compared to more time-consuming genetic ablation experiments. The local application avoids potential systemic effects of microRNA knockdown, therefore allowing the assessment of impacts on heart development only. The method can be adjusted for different stages of chicken embryos (HH13-HH18) as well as for knockdown or targeted overexpression of coding genes.

CONCLUSION: In conclusion our method allows targeted and locally restricted delivery of Antagomirs to the heart leading to successful knockdown of microRNA function. This method enables rapid phenotypic assessment, for example by gene expression analysis of multiple cardiac genes.}, } @article {pmid30496538, year = {2018}, author = {Nuckels, RJ and Nice, CC and García, DM}, title = {Duplicated Myosin V Genes in Teleosts Show Evolutionary Rate Variations among the Motor and Cargo Binding Domains.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evy258}, pmid = {30496538}, issn = {1759-6653}, abstract = {We analyzed evolutionary rates of conserved, duplicated myosin V (myo5) genes in nine teleost species to examine the outcomes of duplication events. Syntenic analysis and ancestral chromosome mapping suggest one tandem gene duplication event leading to the appearance of myo5a and myo5c, two rounds of whole genome duplication for vertebrates, and an additional round of whole genome duplication for teleosts account for the presence and location of the myo5 genes and their duplicates in teleosts and other vertebrates and the timing of the duplication events. Phylogenetic analyses reveal a previously unidentified myo5 clade that we refer to now as myo5bb. Analysis using dN/dS rate comparisons revealed large regions within duplicated myo5 genes that are highly conserved. Codons identified in other studies as encoding functionally important portions of the Myo5a and Myo5b proteins are shown to be highly conserved within the newly identified myo5bb clade and in other myo5 duplicates. As much as 30% of 319 codons encoding the cargo binding domain in the myo5aa genes are conserved in all three codon positions in nine teleost species. For the myo5bb cargo binding domain, 6.6% of 336 codons have zero substitutions in all nine teleost species. Using molecular evolution assays, we identify the myo5bb branch as being subject to evolutionary rate variation with the cargo binding domain, having 20% of the sites under positive selection and the motor domain having 8% of its sites under positive selection. The high number of invariant codons coupled with relatively high dN/dS values in the region of the myo5 genes encoding the ATP binding domain suggests the encoded proteins retain function and may have acquired novel functions associated with changes to the cargo binding domain.}, } @article {pmid30489240, year = {2019}, author = {Li, YX and Wang, NN and Chen, GJ and Du, ZJ}, title = {Cohaesibacter celericrescens sp. nov., isolated from sea catfish.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {255-260}, doi = {10.1099/ijsem.0.003146}, pmid = {30489240}, issn = {1466-5034}, abstract = {A novel Gram-stain-negative, rod-shaped, ivory-white, facultatively anaerobic and catalase-positive bacterium, designated H1304T, was isolated from the gut of sea catfish from Coast of Weihai, China. Optimal growth occurred at 30-33 °C (range, 4-37 °C) and pH 7.0-7.5 (range, pH 6.5-9.0) with 2.0-3.0 % (w/v) NaCl (range, 0.5-4.0 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that H1304T belonged to the genus Cohaesibacter and was most closely related to Cohaesibactermarisflavi CGMCC 1.9157T (96.7 % 16S rRNA gene sequence similarity), Cohaesibactergelatinilyticus MCCC 1A02698T (96.3 %) and Cohaesibacterhaloalkalitolerans KCTC 32038T (96.0 %). The sole isoprenoid quinone was Q-10, the polar lipid profile consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine, glycolipid, an unidentified phospholipid and an unidentified aminolipid. The major fatty acids (>10 %) were C18 : 1ω7c and summed feature 3 (C16 : 1ω7c/C16 : 1ω6c). The DNA G+C content of strain H1304T is 50.8 mol%. Based on the combination of phylogenetic analysis, phenotypic data and chemotaxonomic data, strain H1304T is considered to represent a novel species within the genus Cohaesibacter in the family Cohaesibacteraceae, for which the name Cohaesibacter celericrescens sp. nov. is proposed. The type strain of the new species is H1304T (=KCTC 62075T=MCCC 1H00241T).}, } @article {pmid30489238, year = {2019}, author = {Zhang, H and Li, YQ and Xiao, M and Fang, BZ and Alkhalifah, DHM and Hozzein, WN and Rao, MPN and Li, WJ}, title = {Description of Paracoccus endophyticus sp. nov., isolated from Gastrodia elata Blume.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {261-265}, doi = {10.1099/ijsem.0.003142}, pmid = {30489238}, issn = {1466-5034}, abstract = {A Gram-stain-negative, strictly aerobic, non-motile strain, SYSUP0003T, was isolated from tubers of Gastrodia elata Blume. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSUP0003T belonged to the genus Paracoccus, with the highest sequence similarity to the type strain of Paracoccus sediminis (97.5 %). Strain SYSUP0003T grew at pH 6.0-8.0 and 4-30 °C with optimum growth at pH 7.0 and 28 °C. Strain SYSUP0003T could tolerate up to 1 % (w/v) NaCl and grew optimally in the absence of NaCl. The isoprenoid quinone of strain SYSUP0003T was Q-10. The major fatty acids were C18 : 0, C16 : 0, C10 : 0 3-OH and summed feature 7. The polar lipids were diphosphatidylglycerol (DPG), aminophospholipids (AL), phosphatidylglycerol (PG), phosphatidylcholine (PC) and four unidentified polar lipids (L). The genome size was 3 204 685 bp, with a DNA G+C content of 69.7 mol%. The average nucleotide identity values between strain SYSUP0003T and P. sediminis DSM 26170T (ANIm 84.2 %, ANIb 75.6 %), Paracoccus solventivorans DSM 6637T (ANIm 84.5 %, ANIb 76.9 %) and Paracoccus alkenifer DSM 11593T (ANIm 84.3 %, ANIb 77.3 %) were below the cut-off level (95-96 %) for species delineation. Based on phenotypic, chemotaxonomic and molecular characterizations, strain SYSUP0003T represents a novel species of the genus Paracoccus, for which the name Paracoccus endophyticus sp. nov. is proposed. The type strain is SYSUP0003T (=KCTC 62180T=CGMCC 1.16545T).}, } @article {pmid30489237, year = {2018}, author = {Li, QQ and Chen, X and Zhou, XK and Dong, LM and Xiao, M and Fang, BZ and Li, WJ and Duan, YQ}, title = {Dyella tabacisoli sp. nov., a bacterium isolated from an arable soil sample of Nicotiana tabacum L.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003138}, pmid = {30489237}, issn = {1466-5034}, abstract = {A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated strain L4-6T, was isolated from an arable soil sample of tobacco in Huize, south-western China and subjected to polyphasic taxonomic characterization. The cells showed oxidase-positive and catalase-positive reactions. Growth occurred at 20-35 °C, at pH 5.0-8.0 and with 0-2 % (w/v) NaCl, optimally at 30 °C, pH 6.0-7.0 and 0-1 % (w/v) NaCl. The major respiratory lipoquinone was ubiquinone-8. The predominant cellular fatty acids (>10.0 %) were identified as summed feature 9 (iso-C17 : 1ω9c or C16 : 0 10-methyl), iso-C15 : 0 and iso-C17 : 0. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, two unidentified aminophospholipids and five unidentified aminolipids. The genomic DNA G+C content was 60.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain L4-6T should be affiliated to the genus Dyella and formed a clade with the most closely related organism Dyella soli JS12-10T. 16S rRNA gene sequences similarity analysis showed that strain L4-6T was mostly closely related to D. soli JS12-10T (98.73 %) and Dyella lipolytica DHOB07T (98.02 %). DNA-DNA hybridization data indicated that strain L4-6T represented a novel genomic species belonging to the genus Dyella. The polyphasic taxonomic characteristics indicated that the strain L4-6T represents a novel species of the genus Dyella, for which the name Dyellatabacisoli sp. nov. (type strain L4-6T=CGMCC 1.16273T=KCTC 62035T) is proposed.}, } @article {pmid30489236, year = {2019}, author = {Fang, BZ and Han, MX and Zhang, LY and Jiao, JY and Zhang, XT and Zhang, ZT and Wang, Y and Nie, GX and Li, WJ}, title = {Nocardia aurea sp. nov., a novel actinobacterium isolated from a karstic subterranean environment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {159-164}, doi = {10.1099/ijsem.0.003122}, pmid = {30489236}, issn = {1466-5034}, abstract = {A novel actinobacterium, designated strain SYSU K10002T, was isolated from a soil sample collected from a karst cave in Xingyi county, Guizhou province, south-western China. The taxonomic position of the strain was investigated using a polyphasic approach. Cells of the strain were aerobic and Gram-stain-positive. On the basis of 16S rRNA gene sequence similarities and phylogenetic analysis, strain SYSU K10002T was most closely related to the type strains of Nocardiaaltamirensis NBRC 108246T (99.0 % sequence similarity) and Nocardiatenerifensis NBRC 101015T (98.8 %) and is therefore considered to represent a member of the genus Nocardia. DNA-DNA hybridization values between strain SYSU K10002T and the closely related type strains of the genus Nocardia were less than 70 %. In addition, meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell sugars were arabinose, ribose and galactose. The major isoprenoid quinone was MK-8(H4,ω-cycl), while the major fatty acids (>10 %) were C16 : 0, C18 : 1ω9c and C18 : 0 10-methyl. The polar lipids contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and an unidentified glycolipid. Mycolic acids were present. The genomic DNA G+C content of strain SYSU K10002T was 67.4 mol%. On the basis of phenotypic, genotypic and phylogenetic data, strain SYSU K10002T represents a novel species of the genus Nocardia, for which the name Nocardiaaurea sp. nov. is proposed. The type strain is SYSU K10002T (=KCTC 39849T=DSM 103986T).}, } @article {pmid30488165, year = {2018}, author = {Wang, Y and Zhang, X and Li, Y and Zhen, Q and Wang, Y}, title = {Distribution of Mycelia of Morchella esculenta in Wild Field.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1603-0}, pmid = {30488165}, issn = {1432-0991}, support = {No. 384 (2016)//The Education Department of Jilin province 13th Five-Year science and technology research project/ ; }, abstract = {It was well-known that Morchella esculenta has a life cycle including vegetative hyphae, sclerotia, primordia, and fruiting bodies, but there is no report yet about the influence of mycelial mass on fruiting process. Since 2014, we have developed an ELISA method to detect the content of Morchella esculenta. In this study, we utilized this method to measure the mycelia content, and find the correlation between mycelial content and fruiting in the wild. The study demonstrated the changes of mycelial concentration at different location around fruiting spot.}, } @article {pmid30488164, year = {2018}, author = {Yeh, HY and Line, JE and Hinton, A}, title = {Community-Level Physiological Profiling for Microbial Community Function in Broiler Ceca.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1602-1}, pmid = {30488164}, issn = {1432-0991}, support = {BRF002//U.S. Poultry and Egg Association/ ; }, abstract = {Poultry production is a major agricultural output worldwide. It is known that the gut health of broilers is essential for their growth and for providing wholesome products for human consumption. Previously, the microbial diversity of broiler ceca was studied at the genetic level. However, the functional diversity and metabolic activity of broiler cecal bacterial communities are not fully investigated. Recently, the EcoPlates™ from Biolog, Inc. have been used for characterizing bacterial communities from various environments. In this study, we applied these plates to physiologically profile cecal bacterial communities in broilers. The ceca were aseptically excised from 6-week-old broilers, and their contents were suspended in phosphate buffered saline. The cultures in the EcoPlates™ were incubated at 42 °C for 5 days in an OmniLog® system. Responses of the bacterial communities to the various chemicals as carbon sources were measured on formazan production. The results show sigmoidal growth curves with three phases in all 12 cecal samples. Cecal bacterial communities could not use 11 carbon substrates for carbon sources; instead, they used pyruvic acid methyl ester, glycogen, glucose-1-phosphate and N-acetyl-D-glucosamine most frequently. Each bacterial community metabolized various numbers of the substrates at different rates among broilers. In the future, modification of the culture conditions to mimic the gut environment is needed. More investigations on the effects of nutrients, Salmonella or Campylobacter on physiological functions of cecal bacterial communities will provide insights into the improvement of animal well-being, saving production expenditures for producers and providing safer poultry products for human consumption.}, } @article {pmid30487969, year = {2018}, author = {Hochberg, ME}, title = {An ecosystem framework for understanding and treating disease.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {270-286}, pmid = {30487969}, issn = {2050-6201}, abstract = {Pathogens and cancers are pervasive health risks in the human population. I argue that if we are to better understand disease and its treatment, then we need to take an ecological perspective of disease itself. I generalize and extend an emerging framework that views disease as an ecosystem and many of its components as interacting in a community. I develop the framework for biological etiological agents (BEAs) that multiply within humans-focusing on bacterial pathogens and cancers-but the framework could be extended to include other host and parasite species. I begin by describing why we need an ecosystem framework to understand disease, and the main components and interactions in bacterial and cancer disease ecosystems. Focus is then given to the BEA and how it may proceed through characteristic states, including emergence, growth, spread and regression. The framework is then applied to therapeutic interventions. Central to success is preventing BEA evasion, the best known being antibiotic resistance and chemotherapeutic resistance in cancers. With risks of evasion in mind, I propose six measures that either introduce new components into the disease ecosystem or manipulate existing ones. An ecosystem framework promises to enhance our understanding of disease, BEA and host (co)evolution, and how we can improve therapeutic outcomes.}, } @article {pmid30487634, year = {2018}, author = {}, title = {Science is social.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1619}, doi = {10.1038/s41588-018-0308-4}, pmid = {30487634}, issn = {1546-1718}, } @article {pmid30487633, year = {2018}, author = {}, title = {Chinese mega 'LHC', Scotland's research and Plan S consultation.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {604-605}, doi = {10.1038/d41586-018-07531-6}, pmid = {30487633}, issn = {1476-4687}, } @article {pmid30487632, year = {2018}, author = {Faleiros, G}, title = {How science supports São Paulo.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S179-S181}, doi = {10.1038/d41586-018-07536-1}, pmid = {30487632}, issn = {1476-4687}, } @article {pmid30487631, year = {2018}, author = {Hodson, R}, title = {Digital revolution.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S131}, doi = {10.1038/d41586-018-07500-z}, pmid = {30487631}, issn = {1476-4687}, } @article {pmid30487630, year = {2018}, author = {Segal, M}, title = {How automation is changing work.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S132-S135}, doi = {10.1038/d41586-018-07501-y}, pmid = {30487630}, issn = {1476-4687}, } @article {pmid30487629, year = {2018}, author = {Hecht, J}, title = {Managing expectations of artificial intelligence.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S141-S143}, doi = {10.1038/d41586-018-07504-9}, pmid = {30487629}, issn = {1476-4687}, } @article {pmid30487628, year = {2018}, author = {El-Showk, S}, title = {Saving the digital world.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S144-S146}, doi = {10.1038/d41586-018-07505-8}, pmid = {30487628}, issn = {1476-4687}, } @article {pmid30487627, year = {2018}, author = {Savage, N}, title = {Making digital government a better government.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S136-S137}, doi = {10.1038/d41586-018-07502-x}, pmid = {30487627}, issn = {1476-4687}, } @article {pmid30487626, year = {2018}, author = {Makin, S}, title = {Searching for digital technology's effects on well-being.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S138-S140}, doi = {10.1038/d41586-018-07503-w}, pmid = {30487626}, issn = {1476-4687}, } @article {pmid30487625, year = {2018}, author = {Sengupta, A and Bouterse, S and Allmann, K}, title = {Build an internet for, and from, us all.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {S147-S148}, doi = {10.1038/d41586-018-07506-7}, pmid = {30487625}, issn = {1476-4687}, } @article {pmid30487624, year = {2018}, author = {Lavery, T and Kekeubata, E and Esau, T and Flannery, T and MacLaren, D and Waneagea, J}, title = {Rat and bat hunt helped heal rift from colonial cruelty.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {626}, doi = {10.1038/d41586-018-07548-x}, pmid = {30487624}, issn = {1476-4687}, } @article {pmid30487623, year = {2018}, author = {Bespalov, A and Barnett, AG and Begley, CG}, title = {Industry is more alarmed about reproducibility than academia.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {626}, doi = {10.1038/d41586-018-07549-w}, pmid = {30487623}, issn = {1476-4687}, } @article {pmid30487622, year = {2018}, author = {Suza, WP and Kena, AW and Akromah, R and Mugwanya, N and Zeller, MF}, title = {Fear holds back gene-edited crops - educate the public.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {626}, doi = {10.1038/d41586-018-07547-y}, pmid = {30487622}, issn = {1476-4687}, } @article {pmid30487621, year = {2018}, author = {Johnson, KL and Banwart, SA and Peacock, CL and Blake, L}, title = {Heat and soil vie for waste to cut emissions.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {626}, doi = {10.1038/d41586-018-07546-z}, pmid = {30487621}, issn = {1476-4687}, } @article {pmid30487620, year = {2018}, author = {}, title = {Ban bullying in science.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {600}, doi = {10.1038/d41586-018-07529-0}, pmid = {30487620}, issn = {1476-4687}, } @article {pmid30487619, year = {2018}, author = {Else, H}, title = {Does science have a bullying problem?.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {616-618}, doi = {10.1038/d41586-018-07532-5}, pmid = {30487619}, issn = {1476-4687}, } @article {pmid30487618, year = {2018}, author = {Kara, E}, title = {A glimpse into the heart of a quasar.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {636-637}, doi = {10.1038/d41586-018-07538-z}, pmid = {30487618}, issn = {1476-4687}, mesh = {*Astronomy ; Extraterrestrial Environment ; *Rotation ; }, } @article {pmid30487617, year = {2018}, author = {Abram, NJ}, title = {Past warming events in the Arctic linked to shifting winds in the Antarctic.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {630-631}, doi = {10.1038/d41586-018-07495-7}, pmid = {30487617}, issn = {1476-4687}, mesh = {Antarctic Regions ; Arctic Regions ; *Climate ; *Ice ; Wind ; }, } @article {pmid30487615, year = {2018}, author = {Dehmamy, N and Milanlouei, S and Barabási, AL}, title = {A structural transition in physical networks.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {676-680}, doi = {10.1038/s41586-018-0726-6}, pmid = {30487615}, issn = {1476-4687}, support = {P01 HL132825/HL/NHLBI NIH HHS/United States ; }, abstract = {In many physical networks, including neurons in the brain1,2, three-dimensional integrated circuits3 and underground hyphal networks4, the nodes and links are physical objects that cannot intersect or overlap with each other. To take this into account, non-crossing conditions can be imposed to constrain the geometry of networks, which consequently affects how they form, evolve and function. However, these constraints are not included in the theoretical frameworks that are currently used to characterize real networks5-7. Most tools for laying out networks are variants of the force-directed layout algorithm8,9-which assumes dimensionless nodes and links-and are therefore unable to reveal the geometry of densely packed physical networks. Here we develop a modelling framework that accounts for the physical sizes of nodes and links, allowing us to explore how non-crossing conditions affect the geometry of a network. For small link thicknesses, we observe a weakly interacting regime in which link crossings are avoided via local link rearrangements, without altering the overall geometry of the layout compared to the force-directed layout. Once the link thickness exceeds a threshold, a strongly interacting regime emerges in which multiple geometric quantities, such as the total link length and the link curvature, scale with the link thickness. We show that the crossover between the two regimes is driven by the non-crossing condition, which allows us to derive the transition point analytically and show that networks with large numbers of nodes will ultimately exist in the strongly interacting regime. We also find that networks in the weakly interacting regime display a solid-like response to stress, whereas in the strongly interacting regime they behave in a gel-like fashion. Networks in the weakly interacting regime are amenable to 3D printing and so can be used to visualize network geometry, and the strongly interacting regime provides insights into the scaling of the sizes of densely packed mammalian brains.}, } @article {pmid30487614, year = {2018}, author = {Buizert, C and Sigl, M and Severi, M and Markle, BR and Wettstein, JJ and McConnell, JR and Pedro, JB and Sodemann, H and Goto-Azuma, K and Kawamura, K and Fujita, S and Motoyama, H and Hirabayashi, M and Uemura, R and Stenni, B and Parrenin, F and He, F and Fudge, TJ and Steig, EJ}, title = {Abrupt ice-age shifts in southern westerly winds and Antarctic climate forced from the north.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {681-685}, doi = {10.1038/s41586-018-0727-5}, pmid = {30487614}, issn = {1476-4687}, support = {ANT-1643394//US National Science Foundation/International ; ANT-1643355//US National Science Foundation/International ; AGS-1502990//US National Science Foundation/International ; DE-AC05-00OR22725//Department of Energy/International ; }, abstract = {The mid-latitude westerly winds of the Southern Hemisphere play a central role in the global climate system via Southern Ocean upwelling1, carbon exchange with the deep ocean2, Agulhas leakage (transport of Indian Ocean waters into the Atlantic)3 and possibly Antarctic ice-sheet stability4. Meridional shifts of the Southern Hemisphere westerly winds have been hypothesized to occur5,6 in parallel with the well-documented shifts of the intertropical convergence zone7 in response to Dansgaard-Oeschger (DO) events- abrupt North Atlantic climate change events of the last ice age. Shifting moisture pathways to West Antarctica8 are consistent with this view but may represent a Pacific teleconnection pattern forced from the tropics9. The full response of the Southern Hemisphere atmospheric circulation to the DO cycle and its impact on Antarctic temperature remain unclear10. Here we use five ice cores synchronized via volcanic markers to show that the Antarctic temperature response to the DO cycle can be understood as the superposition of two modes: a spatially homogeneous oceanic 'bipolar seesaw' mode that lags behind Northern Hemisphere climate by about 200 years, and a spatially heterogeneous atmospheric mode that is synchronous with abrupt events in the Northern Hemisphere. Temperature anomalies of the atmospheric mode are similar to those associated with present-day Southern Annular Mode variability, rather than the Pacific-South American pattern. Moreover, deuterium-excess records suggest a zonally coherent migration of the Southern Hemisphere westerly winds over all ocean basins in phase with Northern Hemisphere climate. Our work provides a simple conceptual framework for understanding circum-Antarctic temperature variations forced by abrupt Northern Hemisphere climate change. We provide observational evidence of abrupt shifts in the Southern Hemisphere westerly winds, which have previously documented1-3 ramifications for global ocean circulation and atmospheric carbon dioxide. These coupled changes highlight the necessity of a global, rather than a purely North Atlantic, perspective on the DO cycle.}, } @article {pmid30487613, year = {2018}, author = {, }, title = {Spatially resolved rotation of the broad-line region of a quasar at sub-parsec scale.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {657-660}, doi = {10.1038/s41586-018-0731-9}, pmid = {30487613}, issn = {1476-4687}, abstract = {The broadening of atomic emission lines by high-velocity motion of gas near accreting supermassive black holes is an observational hallmark of quasars1. Observations of broad emission lines could potentially constrain the mechanism for transporting gas inwards through accretion disks or outwards through winds2. The size of regions for which broad emission lines are observed (broad-line regions) has been estimated by measuring the delay in light travel time between the variable brightness of the accretion disk continuum and the emission lines3-a method known as reverberation mapping. In some models the emission lines arise from a continuous outflow4, whereas in others they arise from orbiting gas clouds5. Directly imaging such regions has not hitherto been possible because of their small angular size (less than 10-4 arcseconds3,6). Here we report a spatial offset (with a spatial resolution of 10-5 arcseconds, or about 0.03 parsecs for a distance of 550 million parsecs) between the red and blue photo-centres of the broad Paschen-α line of the quasar 3C 273 perpendicular to the direction of its radio jet. This spatial offset corresponds to a gradient in the velocity of the gas and thus implies that the gas is orbiting the central supermassive black hole. The data are well fitted by a broad-line-region model of a thick disk of gravitationally bound material orbiting a black hole of 3 × 108 solar masses. We infer a disk radius of 150 light days; a radius of 100-400 light days was found previously using reverberation mapping7-9. The rotation axis of the disk aligns in inclination and position angle with the radio jet. Our results support the methods that are often used to estimate the masses of accreting supermassive black holes and to study their evolution over cosmic time.}, } @article {pmid30487609, year = {2019}, author = {Zhou, HL and Zhang, R and Anand, P and Stomberski, CT and Qian, Z and Hausladen, A and Wang, L and Rhee, EP and Parikh, SM and Karumanchi, SA and Stamler, JS}, title = {Metabolic reprogramming by the S-nitroso-CoA reductase system protects against kidney injury.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {96-100}, doi = {10.1038/s41586-018-0749-z}, pmid = {30487609}, issn = {1476-4687}, support = {P01 HL075443/HL/NHLBI NIH HHS/United States ; P01 HL128192/HL/NHLBI NIH HHS/United States ; R01 DK119506/DK/NIDDK NIH HHS/United States ; R01 HL126900/HL/NHLBI NIH HHS/United States ; }, abstract = {Endothelial nitric oxide synthase (eNOS) is protective against kidney injury, but the molecular mechanisms of this protection are poorly understood1,2. Nitric oxide-based cellular signalling is generally mediated by protein S-nitrosylation, the oxidative modification of Cys residues to form S-nitrosothiols (SNOs). S-nitrosylation regulates proteins in all functional classes, and is controlled by enzymatic machinery that includes S-nitrosylases and denitrosylases, which add and remove SNO from proteins, respectively3,4. In Saccharomyces cerevisiae, the classic metabolic intermediate co-enzyme A (CoA) serves as an endogenous source of SNOs through its conjugation with nitric oxide to form S-nitroso-CoA (SNO-CoA), and S-nitrosylation of proteins by SNO-CoA is governed by its cognate denitrosylase, SNO-CoA reductase (SCoR)5. Mammals possess a functional homologue of yeast SCoR, an aldo-keto reductase family member (AKR1A1)5 with an unknown physiological role. Here we report that the SNO-CoA-AKR1A1 system is highly expressed in renal proximal tubules, where it transduces the activity of eNOS in reprogramming intermediary metabolism, thereby protecting kidneys against acute kidney injury. Specifically, deletion of Akr1a1 in mice to reduce SCoR activity increased protein S-nitrosylation, protected against acute kidney injury and improved survival, whereas this protection was lost when Enos (also known as Nos3) was also deleted. Metabolic profiling coupled with unbiased mass spectrometry-based SNO-protein identification revealed that protection by the SNO-CoA-SCoR system is mediated by inhibitory S-nitrosylation of pyruvate kinase M2 (PKM2) through a novel locus of regulation, thereby balancing fuel utilization (through glycolysis) with redox protection (through the pentose phosphate shunt). Targeted deletion of PKM2 from mouse proximal tubules recapitulated precisely the protective and mechanistic effects of S-nitrosylation in Akr1a1-/- mice, whereas Cys-mutant PKM2, which is refractory to S-nitrosylation, negated SNO-CoA bioactivity. Our results identify a physiological function of the SNO-CoA-SCoR system in mammals, describe new regulation of renal metabolism and of PKM2 in differentiated tissues, and offer a novel perspective on kidney injury with therapeutic implications.}, } @article {pmid30487608, year = {2018}, author = {Mamidi, A and Prawiro, C and Seymour, PA and de Lichtenberg, KH and Jackson, A and Serup, P and Semb, H}, title = {Mechanosignalling via integrins directs fate decisions of pancreatic progenitors.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {114-118}, doi = {10.1038/s41586-018-0762-2}, pmid = {30487608}, issn = {1476-4687}, abstract = {The pancreas originates from two epithelial evaginations of the foregut, which consist of multipotent epithelial progenitors that organize into a complex tubular epithelial network. The trunk domain of each epithelial branch consists of bipotent pancreatic progenitors (bi-PPs) that give rise to both duct and endocrine lineages, whereas the tips give rise to acinar cells1. Here we identify the extrinsic and intrinsic signalling mechanisms that coordinate the fate-determining transcriptional events underlying these lineage decisions1,2. Single-cell analysis of pancreatic bipotent pancreatic progenitors derived from human embryonic stem cells reveal that cell confinement is a prerequisite for endocrine specification, whereas spreading drives the progenitors towards a ductal fate. Mechanistic studies identify the interaction of extracellular matrix (ECM) with integrin α5 as the extracellular cue that cell-autonomously, via the F-actin-YAP1-Notch mechanosignalling axis, controls the fate of bipotent pancreatic progenitors. Whereas ECM-integrin α5 signalling promotes differentiation towards the duct lineage, endocrinogenesis is stimulated when this signalling cascade is disrupted. This cascade can be disrupted pharmacologically or genetically to convert bipotent pancreatic progenitors derived from human embryonic stem cells to hormone-producing islet cells. Our findings identify the cell-extrinsic and intrinsic mechanotransduction pathway that acts as gatekeeper in the fate decisions of bipotent pancreatic progenitors in the developing pancreas.}, } @article {pmid30487607, year = {2018}, author = {Dubbury, SJ and Boutz, PL and Sharp, PA}, title = {CDK12 regulates DNA repair genes by suppressing intronic polyadenylation.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {141-145}, doi = {10.1038/s41586-018-0758-y}, pmid = {30487607}, issn = {1476-4687}, support = {T32 GM007287/GM/NIGMS NIH HHS/United States ; P01 CA042063/CA/NCI NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; R01 CA133404/CA/NCI NIH HHS/United States ; R01 GM034277/GM/NIGMS NIH HHS/United States ; }, abstract = {Mutations that attenuate homologous recombination (HR)-mediated repair promote tumorigenesis and sensitize cells to chemotherapeutics that cause replication fork collapse, a phenotype known as 'BRCAness'1. BRCAness tumours arise from loss-of-function mutations in 22 genes1. Of these genes, all but one (CDK12) function directly in the HR repair pathway1. CDK12 phosphorylates serine 2 of the RNA polymerase II C-terminal domain heptapeptide repeat2-7, a modification that regulates transcription elongation, splicing, and cleavage and polyadenylation8,9. Genome-wide expression studies suggest that depletion of CDK12 abrogates the expression of several HR genes relatively specifically, thereby blunting HR repair3-7,10,11. This observation suggests that the mutational status of CDK12 may predict sensitivity to targeted treatments against BRCAness, such as PARP1 inhibitors, and that CDK12 inhibitors may induce sensitization of HR-competent tumours to these treatments6,7,10,11. Despite growing clinical interest, the mechanism by which CDK12 regulates HR genes remains unknown. Here we show that CDK12 globally suppresses intronic polyadenylation events in mouse embryonic stem cells, enabling the production of full-length gene products. Many HR genes harbour more intronic polyadenylation sites than other expressed genes, and these sites are particularly sensitive to loss of CDK12. The cumulative effect of these sites accounts for the enhanced sensitivity of HR gene expression to CDK12 loss, and we find that this mechanism is conserved in human tumours that contain loss-of-function CDK12 mutations. This work clarifies the function of CDK12 and underscores its potential both as a chemotherapeutic target and as a tumour biomarker.}, } @article {pmid30487606, year = {2018}, author = {Meng, X and Liu, X and Guo, X and Jiang, S and Chen, T and Hu, Z and Liu, H and Bai, Y and Xue, M and Hu, R and Sun, SC and Liu, X and Zhou, P and Huang, X and Wei, L and Yang, W and Xu, C}, title = {FBXO38 mediates PD-1 ubiquitination and regulates anti-tumour immunity of T cells.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {130-135}, doi = {10.1038/s41586-018-0756-0}, pmid = {30487606}, issn = {1476-4687}, abstract = {Dysfunctional T cells in the tumour microenvironment have abnormally high expression of PD-1 and antibody inhibitors against PD-1 or its ligand (PD-L1) have become commonly used drugs to treat various types of cancer1-4. The clinical success of these inhibitors highlights the need to study the mechanisms by which PD-1 is regulated. Here we report a mechanism of PD-1 degradation and the importance of this mechanism in anti-tumour immunity in preclinical models. We show that surface PD-1 undergoes internalization, subsequent ubiquitination and proteasome degradation in activated T cells. FBXO38 is an E3 ligase of PD-1 that mediates Lys48-linked poly-ubiquitination and subsequent proteasome degradation. Conditional knockout of Fbxo38 in T cells did not affect T cell receptor and CD28 signalling, but led to faster tumour progression in mice owing to higher levels of PD-1 in tumour-infiltrating T cells. Anti-PD-1 therapy normalized the effect of FBXO38 deficiency on tumour growth in mice, which suggests that PD-1 is the primary target of FBXO38 in T cells. In human tumour tissues and a mouse cancer model, transcriptional levels of FBXO38 and Fbxo38, respectively, were downregulated in tumour-infiltrating T cells. However, IL-2 therapy rescued Fbxo38 transcription and therefore downregulated PD-1 levels in PD-1+ T cells in mice. These data indicate that FBXO38 regulates PD-1 expression and highlight an alternative method to block the PD-1 pathway.}, } @article {pmid30487605, year = {2018}, author = {Turco, MY and Gardner, L and Kay, RG and Hamilton, RS and Prater, M and Hollinshead, MS and McWhinnie, A and Esposito, L and Fernando, R and Skelton, H and Reimann, F and Gribble, FM and Sharkey, A and Marsh, SGE and O'Rahilly, S and Hemberger, M and Burton, GJ and Moffett, A}, title = {Trophoblast organoids as a model for maternal-fetal interactions during human placentation.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {263-267}, doi = {10.1038/s41586-018-0753-3}, pmid = {30487605}, issn = {1476-4687}, support = {MC_UU_12012/3//Medical Research Council/United Kingdom ; MC_UU_12012/5//Medical Research Council/United Kingdom ; 200841/Z/16/Z//Wellcome Trust/United Kingdom ; MR/L020041/1//Medical Research Council/United Kingdom ; }, abstract = {The placenta is the extraembryonic organ that supports the fetus during intrauterine life. Although placental dysfunction results in major disorders of pregnancy with immediate and lifelong consequences for the mother and child, our knowledge of the human placenta is limited owing to a lack of functional experimental models1. After implantation, the trophectoderm of the blastocyst rapidly proliferates and generates the trophoblast, the unique cell type of the placenta. In vivo, proliferative villous cytotrophoblast cells differentiate into two main sub-populations: syncytiotrophoblast, the multinucleated epithelium of the villi responsible for nutrient exchange and hormone production, and extravillous trophoblast cells, which anchor the placenta to the maternal decidua and transform the maternal spiral arteries2. Here we describe the generation of long-term, genetically stable organoid cultures of trophoblast that can differentiate into both syncytiotrophoblast and extravillous trophoblast. We used human leukocyte antigen (HLA) typing to confirm that the organoids were derived from the fetus, and verified their identities against four trophoblast-specific criteria3. The cultures organize into villous-like structures, and we detected the secretion of placental-specific peptides and hormones, including human chorionic gonadotropin (hCG), growth differentiation factor 15 (GDF15) and pregnancy-specific glycoprotein (PSG) by mass spectrometry. The organoids also differentiate into HLA-G+ extravillous trophoblast cells, which vigorously invade in three-dimensional cultures. Analysis of the methylome reveals that the organoids closely resemble normal first trimester placentas. This organoid model will be transformative for studying human placental development and for investigating trophoblast interactions with the local and systemic maternal environment.}, } @article {pmid30487604, year = {2018}, author = {Li, Y and Zhang, Z and Chen, J and Liu, W and Lai, W and Liu, B and Li, X and Liu, L and Xu, S and Dong, Q and Wang, M and Duan, X and Tan, J and Zheng, Y and Zhang, P and Fan, G and Wong, J and Xu, GL and Wang, Z and Wang, H and Gao, S and Zhu, B}, title = {Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {136-140}, doi = {10.1038/s41586-018-0751-5}, pmid = {30487604}, issn = {1476-4687}, abstract = {Postnatal growth of mammalian oocytes is accompanied by a progressive gain of DNA methylation, which is predominantly mediated by DNMT3A, a de novo DNA methyltransferase1,2. Unlike the genome of sperm and most somatic cells, the oocyte genome is hypomethylated in transcriptionally inert regions2-4. However, how such a unique feature of the oocyte methylome is determined and its contribution to the developmental competence of the early embryo remains largely unknown. Here we demonstrate the importance of Stella, a factor essential for female fertility5-7, in shaping the oocyte methylome in mice. Oocytes that lack Stella acquire excessive DNA methylation at the genome-wide level, including in the promoters of inactive genes. Such aberrant hypermethylation is partially inherited by two-cell-stage embryos and impairs zygotic genome activation. Mechanistically, the loss of Stella leads to ectopic nuclear accumulation of the DNA methylation regulator UHRF18,9, which results in the mislocalization of maintenance DNA methyltransferase DNMT1 in the nucleus. Genetic analysis confirmed the primary role of UHRF1 and DNMT1 in generating the aberrant DNA methylome in Stella-deficient oocytes. Stella therefore safeguards the unique oocyte epigenome by preventing aberrant de novo DNA methylation mediated by DNMT1 and UHRF1.}, } @article {pmid30487603, year = {2018}, author = {Drescher, L and Kornilov, O and Witting, T and Reitsma, G and Monserud, N and Rouzée, A and Mikosch, J and Vrakking, MJJ and Schütte, B}, title = {Extreme-ultraviolet refractive optics.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {91-94}, doi = {10.1038/s41586-018-0737-3}, pmid = {30487603}, issn = {1476-4687}, abstract = {Refraction is a well-known optical phenomenon that alters the direction of light waves propagating through matter. Microscopes, lenses and prisms based on refraction are indispensable tools for controlling light beams at visible, infrared, ultraviolet and X-ray wavelengths1. In the past few decades, a range of extreme-ultraviolet and soft-X-ray sources has been developed in laboratory environments2-4 and at large-scale facilities5,6. But the strong absorption of extreme-ultraviolet radiation in matter hinders the development of refractive lenses and prisms in this spectral region, for which reflective mirrors and diffractive Fresnel zone plates7 are instead used for focusing. Here we demonstrate control over the refraction of extreme-ultraviolet radiation by using a gas jet with a density gradient across the profile of the extreme-ultraviolet beam. We produce a gas-phase prism that leads to a frequency-dependent deflection of the beam. The strong deflection near to atomic resonances is further used to develop a deformable refractive lens for extreme-ultraviolet radiation, with low absorption and a focal length that can be tuned by varying the gas pressure. Our results open up a route towards the transfer of refraction-based techniques, which are well established in other spectral regions, to the extreme-ultraviolet domain.}, } @article {pmid30487602, year = {2018}, author = {Zhu, Y and Wang, GZ and Cingöz, O and Goff, SP}, title = {NP220 mediates silencing of unintegrated retroviral DNA.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {278-282}, doi = {10.1038/s41586-018-0750-6}, pmid = {30487602}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; R01 CA030488/CA/NCI NIH HHS/United States ; }, abstract = {The entry of foreign DNA into many mammalian cell types triggers the innate immune system, a complex set of responses to prevent infection by pathogens. One aspect of the response is the potent epigenetic silencing of incoming viral DNAs1, including the extrachromosomal DNAs that are formed immediately after infection by retroviruses. These unintegrated viral DNAs are very poorly transcribed in all cells, even in permissive cells, in contrast to the robust expression that is observed after viral integration2-5. The factors that are responsible for this low expression have not yet been identified. Here we performed a genome-wide CRISPR-Cas9 screen for genes that are required for silencing an integrase-deficient MLV-GFP reporter virus to explore the mechanisms responsible for repression of unintegrated viral DNAs in human cells. Our screen identified the DNA-binding protein NP220, the three proteins (MPP8, TASOR and PPHLN1) that comprise the HUSH complex-which silences proviruses in heterochromatin6 and retrotransposons7,8-the histone methyltransferase SETDB1, and other host factors that are required for silencing. Further tests by chromatin immunoprecipitation showed that NP220 is the key protein that recruits the HUSH complex, SETDB1 and the histone deacetylases HDAC1 and HDAC4 to silence the unintegrated retroviral DNA. Knockout of NP220 accelerates the replication of retroviruses. These experiments identify the molecular machinery that silences extrachromosomal retroviral DNA.}, } @article {pmid30487601, year = {2018}, author = {McGrew, WF and Zhang, X and Fasano, RJ and Schäffer, SA and Beloy, K and Nicolodi, D and Brown, RC and Hinkley, N and Milani, G and Schioppo, M and Yoon, TH and Ludlow, AD}, title = {Atomic clock performance enabling geodesy below the centimetre level.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {87-90}, doi = {10.1038/s41586-018-0738-2}, pmid = {30487601}, issn = {1476-4687}, abstract = {The passage of time is tracked by counting oscillations of a frequency reference, such as Earth's revolutions or swings of a pendulum. By referencing atomic transitions, frequency (and thus time) can be measured more precisely than any other physical quantity, with the current generation of optical atomic clocks reporting fractional performance below the 10-17 level1-5. However, the theory of relativity prescribes that the passage of time is not absolute, but is affected by an observer's reference frame. Consequently, clock measurements exhibit sensitivity to relative velocity, acceleration and gravity potential. Here we demonstrate local optical clock measurements that surpass the current ability to account for the gravitational distortion of space-time across the surface of Earth. In two independent ytterbium optical lattice clocks, we demonstrate unprecedented values of three fundamental benchmarks of clock performance. In units of the clock frequency, we report systematic uncertainty of 1.4 × 10-18, measurement instability of 3.2 × 10-19 and reproducibility characterized by ten blinded frequency comparisons, yielding a frequency difference of [-7 ± (5)stat ± (8)sys] × 10-19, where 'stat' and 'sys' indicate statistical and systematic uncertainty, respectively. Although sensitivity to differences in gravity potential could degrade the performance of the clocks as terrestrial standards of time, this same sensitivity can be used as a very sensitive probe of geopotential5-9. Near the surface of Earth, clock comparisons at the 1 × 10-18 level provide a resolution of one centimetre along the direction of gravity, so the performance of these clocks should enable geodesy beyond the state-of-the-art level. These optical clocks could further be used to explore geophysical phenomena10, detect gravitational waves11, test general relativity12 and search for dark matter13-17.}, } @article {pmid30487600, year = {2018}, author = {Chen, J and Chen, ZJ}, title = {PtdIns4P on dispersed trans-Golgi network mediates NLRP3 inflammasome activation.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {71-76}, doi = {10.1038/s41586-018-0761-3}, pmid = {30487600}, issn = {1476-4687}, abstract = {The NLRP3 inflammasome, which has been linked to human inflammatory diseases, is activated by diverse stimuli. How these stimuli activate NLRP3 is unknown. Here we show that different NLRP3 stimuli lead to disassembly of the trans-Golgi network (TGN). NLRP3 is recruited to the dispersed TGN (dTGN) through ionic bonding between its conserved polybasic region and negatively charged phosphatidylinositol-4-phosphate (PtdIns4P) on the dTGN. The dTGN then serves as a scaffold for NLRP3 aggregation into multiple puncta, leading to polymerization of the adaptor protein ASC, thereby activating the downstream signalling cascade. Disruption of the interaction between NLRP3 and PtdIns4P on the dTGN blocked NLRP3 aggregation and downstream signalling. These results indicate that recruitment of NLRP3 to dTGN is an early and common cellular event that leads to NLRP3 aggregation and activation in response to diverse stimuli.}, } @article {pmid30487227, year = {2018}, author = {Mathôt, S and Naber, M}, title = {There is no evidence that pupil mimicry is a social phenomenon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11565}, doi = {10.1073/pnas.1814429115}, pmid = {30487227}, issn = {1091-6490}, mesh = {Biomimetics ; *Pupil ; *Trust ; }, } @article {pmid30487226, year = {2018}, author = {Prochazkova, E and Prochazkova, L and Giffin, MR and Scholte, HS and De Dreu, CKW and Kret, ME}, title = {Reply to Mathôt and Naber: Neuroimaging shows that pupil mimicry is a social phenomenon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11566-E11567}, doi = {10.1073/pnas.1815545115}, pmid = {30487226}, issn = {1091-6490}, mesh = {Biomimetics ; *Neuroimaging ; *Pupil ; Trust ; }, } @article {pmid30487225, year = {2018}, author = {Milosavljevic, N and Storchi, R and Eleftheriou, CG and Colins, A and Petersen, RS and Lucas, RJ}, title = {Photoreceptive retinal ganglion cells control the information rate of the optic nerve.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11817-E11826}, doi = {10.1073/pnas.1810701115}, pmid = {30487225}, issn = {1091-6490}, support = {268970//European Research Council/International ; MR/N012992/1//Medical Research Council/United Kingdom ; }, abstract = {Information transfer in the brain relies upon energetically expensive spiking activity of neurons. Rates of information flow should therefore be carefully optimized, but mechanisms to control this parameter are poorly understood. We address this deficit in the visual system, where ambient light (irradiance) is predictive of the amount of information reaching the eye and ask whether a neural measure of irradiance can therefore be used to proactively control information flow along the optic nerve. We first show that firing rates for the retina's output neurons [retinal ganglion cells (RGCs)] scale with irradiance and are positively correlated with rates of information and the gain of visual responses. Irradiance modulates firing in the absence of any other visual signal confirming that this is a genuine response to changing ambient light. Irradiance-driven changes in firing are observed across the population of RGCs (including in both ON and OFF units) but are disrupted in mice lacking melanopsin [the photopigment of irradiance-coding intrinsically photosensitive RGCs (ipRGCs)] and can be induced under steady light exposure by chemogenetic activation of ipRGCs. Artificially elevating firing by chemogenetic excitation of ipRGCs is sufficient to increase information flow by increasing the gain of visual responses, indicating that enhanced firing is a cause of increased information transfer at higher irradiance. Our results establish a retinal circuitry driving changes in RGC firing as an active response to alterations in ambient light to adjust the amount of visual information transmitted to the brain.}, } @article {pmid30487224, year = {2018}, author = {Duncan, ID and Radcliff, AB and Heidari, M and Kidd, G and August, BK and Wierenga, LA}, title = {The adult oligodendrocyte can participate in remyelination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11807-E11816}, doi = {10.1073/pnas.1808064115}, pmid = {30487224}, issn = {1091-6490}, abstract = {Endogenous remyelination of the CNS can be robust and restore function, yet in multiple sclerosis it becomes less complete with time. Promoting remyelination is a major therapeutic goal, both to restore function and to protect axons from degeneration. Remyelination is thought to depend on oligodendrocyte progenitor cells, giving rise to nascent remyelinating oligodendrocytes. Surviving, mature oligodendrocytes are largely regarded as being uninvolved. We have examined this question using two large animal models. In the first model, there is extensive demyelination and remyelination of the CNS, yet oligodendrocytes survive, and in recovered animals there is a mix of remyelinated axons interspersed between mature, thick myelin sheaths. Using 2D and 3D light and electron microscopy, we show that many oligodendrocytes are connected to mature and remyelinated myelin sheaths, which we conclude are cells that have reextended processes to contact demyelinated axons while maintaining mature myelin internodes. In the second model in vitamin B12-deficient nonhuman primates, we demonstrate that surviving mature oligodendrocytes extend processes and ensheath demyelinated axons. These data indicate that mature oligodendrocytes can participate in remyelination.}, } @article {pmid30487223, year = {2018}, author = {Li, JF and Dai, YT and Lilljebjörn, H and Shen, SH and Cui, BW and Bai, L and Liu, YF and Qian, MX and Kubota, Y and Kiyoi, H and Matsumura, I and Miyazaki, Y and Olsson, L and Tan, AM and Ariffin, H and Chen, J and Takita, J and Yasuda, T and Mano, H and Johansson, B and Yang, JJ and Yeoh, AE and Hayakawa, F and Chen, Z and Pui, CH and Fioretos, T and Chen, SJ and Huang, JY}, title = {Transcriptional landscape of B cell precursor acute lymphoblastic leukemia based on an international study of 1,223 cases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11711-E11720}, doi = {10.1073/pnas.1814397115}, pmid = {30487223}, issn = {1091-6490}, support = {P30 CA021765/CA/NCI NIH HHS/United States ; P50 GM115279/GM/NIGMS NIH HHS/United States ; R01 CA036401/CA/NCI NIH HHS/United States ; R37 CA036401/CA/NCI NIH HHS/United States ; }, abstract = {Most B cell precursor acute lymphoblastic leukemia (BCP ALL) can be classified into known major genetic subtypes, while a substantial proportion of BCP ALL remains poorly characterized in relation to its underlying genomic abnormalities. We therefore initiated a large-scale international study to reanalyze and delineate the transcriptome landscape of 1,223 BCP ALL cases using RNA sequencing. Fourteen BCP ALL gene expression subgroups (G1 to G14) were identified. Apart from extending eight previously described subgroups (G1 to G8 associated with MEF2D fusions, TCF3-PBX1 fusions, ETV6-RUNX1-positive/ETV6-RUNX1-like, DUX4 fusions, ZNF384 fusions, BCR-ABL1/Ph-like, high hyperdiploidy, and KMT2A fusions), we defined six additional gene expression subgroups: G9 was associated with both PAX5 and CRLF2 fusions; G10 and G11 with mutations in PAX5 (p.P80R) and IKZF1 (p.N159Y), respectively; G12 with IGH-CEBPE fusion and mutations in ZEB2 (p.H1038R); and G13 and G14 with TCF3/4-HLF and NUTM1 fusions, respectively. In pediatric BCP ALL, subgroups G2 to G5 and G7 (51 to 65/67 chromosomes) were associated with low-risk, G7 (with ≤50 chromosomes) and G9 were intermediate-risk, whereas G1, G6, and G8 were defined as high-risk subgroups. In adult BCP ALL, G1, G2, G6, and G8 were associated with high risk, while G4, G5, and G7 had relatively favorable outcomes. This large-scale transcriptome sequence analysis of BCP ALL revealed distinct molecular subgroups that reflect discrete pathways of BCP ALL, informing disease classification and prognostic stratification. The combined results strongly advocate that RNA sequencing be introduced into the clinical diagnostic workup of BCP ALL.}, } @article {pmid30487222, year = {2018}, author = {Bhattacharyya, S and Soniat, MM and Walker, D and Jang, S and Finkelstein, IJ and Harshey, RM}, title = {Phage Mu Gam protein promotes NHEJ in concert with Escherichia coli ligase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11614-E11622}, doi = {10.1073/pnas.1816606115}, pmid = {30487222}, issn = {1091-6490}, support = {K99 GM097177/GM/NIGMS NIH HHS/United States ; R00 GM097177/GM/NIGMS NIH HHS/United States ; P01 CA092584/CA/NCI NIH HHS/United States ; R01 GM120554/GM/NIGMS NIH HHS/United States ; R35 GM118085/GM/NIGMS NIH HHS/United States ; }, abstract = {The Gam protein of transposable phage Mu is an ortholog of eukaryotic and bacterial Ku proteins, which carry out nonhomologous DNA end joining (NHEJ) with the help of dedicated ATP-dependent ligases. Many bacteria carry Gam homologs associated with either complete or defective Mu-like prophages, but the role of Gam in the life cycle of Mu or in bacteria is unknown. Here, we show that MuGam is part of a two-component bacterial NHEJ DNA repair system. Ensemble and single-molecule experiments reveal that MuGam binds to DNA ends, slows the progress of RecBCD exonuclease, promotes binding of NAD+-dependent Escherichia coli ligase A, and stimulates ligation. In vivo, Gam equally promotes both precise and imprecise joining of restriction enzyme-digested linear plasmid DNA, as well as of a double-strand break (DSB) at an engineered I-SceI site in the chromosome. Cell survival after the induced DSB is specific to the stationary phase. In long-term growth competition experiments, particularly upon treatment with a clastogen, the presence of gam in a Mu lysogen confers a distinct fitness advantage. We also show that the role of Gam in the life of phage Mu is related not to transposition but to protection of genomic Mu copies from RecBCD when viral DNA packaging begins. Taken together, our data show that MuGam provides bacteria with an NHEJ system and suggest that the resulting fitness advantage is a reason that bacteria continue to retain the gam gene in the absence of an intact prophage.}, } @article {pmid30487221, year = {2018}, author = {Hernandez-Miranda, LR and Ibrahim, DM and Ruffault, PL and Larrosa, M and Balueva, K and Müller, T and Weerd, W and Stolte-Dijkstra, I and Hostra, RMW and Brunet, JF and Fortin, G and Mundlos, S and Birchmeier, C}, title = {Mutation in LBX1/Lbx1 precludes transcription factor cooperativity and causes congenital hypoventilation in humans and mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13021-13026}, doi = {10.1073/pnas.1813520115}, pmid = {30487221}, issn = {1091-6490}, abstract = {The respiratory rhythm is generated by the preBötzinger complex in the medulla oblongata, and is modulated by neurons in the retrotrapezoid nucleus (RTN), which are essential for accelerating respiration in response to high CO2 Here we identify a LBX1 frameshift (LBX1FS) mutation in patients with congenital central hypoventilation. The mutation alters the C-terminal but not the DNA-binding domain of LBX1 Mice with the analogous mutation recapitulate the breathing deficits found in humans. Furthermore, the mutation only interferes with a small subset of Lbx1 functions, and in particular with development of RTN neurons that coexpress Lbx1 and Phox2b. Genome-wide analyses in a cell culture model show that Lbx1FS and wild-type Lbx1 proteins are mostly bound to similar sites, but that Lbx1FS is unable to cooperate with Phox2b. Thus, our analyses on Lbx1FS (dys)function reveals an unusual pathomechanism; that is, a mutation that selectively interferes with the ability of Lbx1 to cooperate with Phox2b, and thus impairs the development of a small subpopulation of neurons essential for respiratory control.}, } @article {pmid30487220, year = {2018}, author = {Moritz, M and Behnke, R and Beitl, CM and Bliege Bird, R and Chiaravalloti, RM and Clark, JK and Crabtree, SA and Downey, SS and Hamilton, IM and Phang, SC and Scholte, P and Wilson, JA}, title = {Emergent sustainability in open property regimes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {12859-12867}, doi = {10.1073/pnas.1812028115}, pmid = {30487220}, issn = {1091-6490}, abstract = {Current theoretical models of the commons assert that common-pool resources can only be managed sustainably with clearly defined boundaries around both communities and the resources that they use. In these theoretical models, open access inevitably leads to a tragedy of the commons. However, in many open-access systems, use of common-pool resources seems to be sustainable over the long term (i.e., current resource use does not threaten use of common-pool resources for future generations). Here, we outline the conditions that support sustainable resource use in open property regimes. We use the conceptual framework of complex adaptive systems to explain how processes within and couplings between human and natural systems can lead to the emergence of efficient, equitable, and sustainable resource use. We illustrate these dynamics in eight case studies of different social-ecological systems, including mobile pastoralism, marine and freshwater fisheries, swidden agriculture, and desert foraging. Our theoretical framework identifies eight conditions that are critical for the emergence of sustainable use of common-pool resources in open property regimes. In addition, we explain how changes in boundary conditions may push open property regimes to either common property regimes or a tragedy of the commons. Our theoretical model of emergent sustainability helps us to understand the diversity and dynamics of property regimes across a wide range of social-ecological systems and explains the enigma of open access without a tragedy. We recommend that policy interventions in such self-organizing systems should focus on managing the conditions that are critical for the emergence and persistence of sustainability.}, } @article {pmid30487219, year = {2018}, author = {Chen, S and Giannakou, A and Wyman, S and Gruzas, J and Golas, J and Zhong, W and Loreth, C and Sridharan, L and Yamin, TT and Damelin, M and Geles, KG}, title = {Cancer-associated fibroblasts suppress SOX2-induced dysplasia in a lung squamous cancer coculture.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11671-E11680}, doi = {10.1073/pnas.1803718115}, pmid = {30487219}, issn = {1091-6490}, abstract = {Tumorigenesis depends on intricate interactions between genetically altered tumor cells and their surrounding microenvironment. While oncogenic drivers in lung squamous carcinoma (LUSC) have been described, the role of stroma in modulating tissue architecture, particularly cell polarity, remains unclear. Here, we report the establishment of a 3D coculture system of LUSC epithelial cells with cancer-associated fibroblasts (CAFs) and extracellular matrix that together capture key components of the tumor microenvironment (TME). Single LUSC epithelial cells develop into acinar-like structures with 0.02% efficiency, and addition of CAFs provides proper tumor-stromal interactions within an appropriate 3D architectural context. Using this model, we recapitulate key pathological changes during tumorigenesis, from hyperplasia to dysplasia and eventually invasion, in malignant LUSC spheroids that undergo phenotypic switching in response to cell intrinsic and extrinsic changes. Overexpression of SOX2 is sufficient to mediate the transition from hyperplasia to dysplasia in LUSC spheroids, while the presence of CAFs makes them invasive. Unexpectedly, CAFs suppress the activity of high SOX2 levels, restore hyperplasia, and enhance the formation of acinar-like structures. Taken together, these observations suggest that stromal factors can override cell intrinsic oncogenic changes in determining the disease phenotype, thus providing fundamental evidence for the existence of dynamic reciprocity between the nucleus and the TME of LUSC.}, } @article {pmid30487218, year = {2018}, author = {Mohiuddin, M and Evans, TJ and Rahman, MM and Keka, IS and Tsuda, M and Sasanuma, H and Takeda, S}, title = {SUMOylation of PCNA by PIAS1 and PIAS4 promotes template switch in the chicken and human B cell lines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12793-12798}, doi = {10.1073/pnas.1716349115}, pmid = {30487218}, issn = {1091-6490}, mesh = {Animals ; B-Lymphocytes/*metabolism ; Cell Cycle/genetics ; Cell Line ; Chickens/*genetics ; DNA Damage/genetics ; DNA Repair/genetics ; DNA Replication/genetics ; Gene Conversion/genetics ; Genes, Immunoglobulin/genetics ; Humans ; Immunoglobulin Variable Region/genetics ; Poly-ADP-Ribose Binding Proteins/*genetics ; Proliferating Cell Nuclear Antigen/*genetics ; Protein Inhibitors of Activated STAT/*genetics ; Sumoylation/*genetics ; Ubiquitin-Protein Ligases/genetics ; }, abstract = {DNA damage tolerance (DDT) releases replication blockage caused by damaged nucleotides on template strands employing two alternative pathways, error-prone translesion DNA synthesis (TLS) and error-free template switch (TS). Lys164 of proliferating cell nuclear antigen (PCNA) is SUMOylated during the physiological cell cycle. To explore the role for SUMOylation of PCNA in DDT, we characterized chicken DT40 and human TK6 B cells deficient in the PIAS1 and PIAS4 small ubiquitin-like modifier (SUMO) E3 ligases. DT40 cells have a unique advantage in the phenotypic analysis of DDT as they continuously diversify their immunoglobulin (Ig) variable genes by TLS and TS [Ig gene conversion (GC)], both relieving replication blocks at abasic sites without accompanying by DNA breakage. Remarkably, PIAS1-/- /PIAS4-/- cells displayed a multifold decrease in SUMOylation of PCNA at Lys164 and over a 90% decrease in the rate of TS. Likewise, PIAS1-/- /PIAS4-/- TK6 cells showed a shift of DDT from TS to TLS at a chemosynthetic UV lesion inserted into the genomic DNA. The PCNAK164R/K164R mutation caused a ∼90% decrease in the rate of Ig GC and no additional impact on PIAS1-/- /PIAS4-/- cells. This epistatic relationship between the PCNAK164R/K164R and the PIAS1-/- /PIAS4-/- mutations suggests that PIAS1 and PIAS4 promote TS mainly through SUMOylation of PCNA at Lys164. This idea is further supported by the data that overexpression of a PCNA-SUMO1 chimeric protein restores defects in TS in PIAS1-/- /PIAS4-/- cells. In conclusion, SUMOylation of PCNA at Lys164 promoted by PIAS1 and PIAS4 ensures the error-free release of replication blockage during physiological DNA replication in metazoan cells.}, } @article {pmid30487217, year = {2018}, author = {Nieto-Rostro, M and Ramgoolam, K and Pratt, WS and Kulik, A and Dolphin, AC}, title = {Ablation of α2δ-1 inhibits cell-surface trafficking of endogenous N-type calcium channels in the pain pathway in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12043-E12052}, doi = {10.1073/pnas.1811212115}, pmid = {30487217}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 098360/Z/12/Z//Wellcome Trust/United Kingdom ; }, abstract = {The auxiliary α2δ calcium channel subunits play key roles in voltage-gated calcium channel function. Independent of this, α2δ-1 has also been suggested to be important for synaptogenesis. Using an epitope-tagged knockin mouse strategy, we examined the effect of α2δ-1 on CaV2.2 localization in the pain pathway in vivo, where CaV2.2 is important for nociceptive transmission and α2δ-1 plays a critical role in neuropathic pain. We find CaV2.2 is preferentially expressed on the plasma membrane of calcitonin gene-related peptide-positive small nociceptors. This is paralleled by strong presynaptic expression of CaV2.2 in the superficial spinal cord dorsal horn. EM-immunogold localization shows CaV2.2 predominantly in active zones of glomerular primary afferent terminals. Genetic ablation of α2δ-1 abolishes CaV2.2 cell-surface expression in dorsal root ganglion neurons and dramatically reduces dorsal horn expression. There was no effect of α2δ-1 knockout on other dorsal horn pre- and postsynaptic markers, indicating the primary afferent pathways are not otherwise affected by α2δ-1 ablation.}, } @article {pmid30487216, year = {2018}, author = {Maywood, ES and Elliott, TS and Patton, AP and Krogager, TP and Chesham, JE and Ernst, RJ and Beránek, V and Brancaccio, M and Chin, JW and Hastings, MH}, title = {Translational switching of Cry1 protein expression confers reversible control of circadian behavior in arrhythmic Cry-deficient mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12388-E12397}, doi = {10.1073/pnas.1811438115}, pmid = {30487216}, issn = {1091-6490}, support = {MC_U105170643//Medical Research Council/United Kingdom ; MC_U105181009//Medical Research Council/United Kingdom ; MC_UP_A024_1008//Medical Research Council/United Kingdom ; }, abstract = {The suprachiasmatic nucleus (SCN) is the principal circadian clock of mammals, coordinating daily rhythms of physiology and behavior. Circadian timing pivots around self-sustaining transcriptional-translational negative feedback loops (TTFLs), whereby CLOCK and BMAL1 drive the expression of the negative regulators Period and Cryptochrome (Cry). Global deletion of Cry1 and Cry2 disables the TTFL, resulting in arrhythmicity in downstream behaviors. We used this highly tractable biology to further develop genetic code expansion (GCE) as a translational switch to achieve reversible control of a biologically relevant protein, Cry1, in the SCN. This employed an orthogonal aminoacyl-tRNA synthetase/tRNACUA pair delivered to the SCN by adeno-associated virus (AAV) vectors, allowing incorporation of a noncanonical amino acid (ncAA) into AAV-encoded Cry1 protein carrying an ectopic amber stop codon. Thus, translational readthrough and Cry1 expression were conditional on the supply of ncAA via culture medium or drinking water and were restricted to neurons by synapsin-dependent expression of aminoacyl tRNA-synthetase. Activation of Cry1 translation by ncAA in neurons of arrhythmic Cry-null SCN slices immediately and dose-dependently initiated TTFL circadian rhythms, which dissipated rapidly after ncAA withdrawal. Moreover, genetic activation of the TTFL in SCN neurons rapidly and reversibly initiated circadian behavior in otherwise arrhythmic Cry-null mice, with rhythm amplitude being determined by the number of transduced SCN neurons. Thus, Cry1 does not specify the development of circadian circuitry and competence but is essential for its labile and rapidly reversible activation. This demonstrates reversible control of mammalian behavior using GCE-based translational switching, a method of potentially broad neurobiological interest.}, } @article {pmid30487215, year = {2018}, author = {Englert, C}, title = {Temperature throws a developmental switch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12553-12555}, doi = {10.1073/pnas.1818216115}, pmid = {30487215}, issn = {1091-6490}, mesh = {Animals ; Diapause ; *Fundulidae ; Temperature ; *Vitamin D ; Vitamins ; }, } @article {pmid30487214, year = {2018}, author = {Henrici, RC and Sutherland, CJ}, title = {Alternative pathway to reduced artemisinin susceptibility in Plasmodium falciparum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12556-12558}, doi = {10.1073/pnas.1818287115}, pmid = {30487214}, issn = {1091-6490}, mesh = {*Artemisinins ; Mutation ; *Plasmodium falciparum ; }, } @article {pmid30487213, year = {2018}, author = {Sun, T and Zhao, S and Chen, W and Zhai, D and Dong, J and Wang, Y and Zhang, S and Han, A and Gu, L and Yu, R and Wen, X and Ren, H and Xu, L and Chen, C and Peng, Q and Wang, D and Li, Y}, title = {Single-atomic cobalt sites embedded in hierarchically ordered porous nitrogen-doped carbon as a superior bifunctional electrocatalyst.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12692-12697}, doi = {10.1073/pnas.1813605115}, pmid = {30487213}, issn = {1091-6490}, abstract = {Exploring efficient and cost-effective catalysts to replace precious metal catalysts, such as Pt, for electrocatalytic oxygen reduction reaction (ORR) and hydrogen evolution reaction (HER) holds great promise for renewable energy technologies. Herein, we prepare a type of Co catalyst with single-atomic Co sites embedded in hierarchically ordered porous N-doped carbon (Co-SAS/HOPNC) through a facile dual-template cooperative pyrolysis approach. The desirable combination of highly dispersed isolated atomic Co-N4 active sites, large surface area, high porosity, and good conductivity gives rise to an excellent catalytic performance. The catalyst exhibits outstanding performance for ORR in alkaline medium with a half-wave potential (E1/2) of 0.892 V, which is 53 mV more positive than that of Pt/C, as well as a high tolerance of methanol and great stability. The catalyst also shows a remarkable catalytic performance for HER with distinctly high turnover frequencies of 0.41 and 3.8 s-1 at an overpotential of 100 and 200 mV, respectively, together with a long-term durability in acidic condition. Experiments and density functional theory (DFT) calculations reveal that the atomically isolated single Co sites and the structural advantages of the unique 3D hierarchical porous architecture synergistically contribute to the high catalytic activity.}, } @article {pmid30487212, year = {2018}, author = {Kim, HT and Goldberg, AL}, title = {UBL domain of Usp14 and other proteins stimulates proteasome activities and protein degradation in cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11642-E11650}, doi = {10.1073/pnas.1808731115}, pmid = {30487212}, issn = {1091-6490}, support = {R01 GM051923/GM/NIGMS NIH HHS/United States ; }, abstract = {The best-known function of ubiquitin-like (UBL) domains in proteins is to enable their binding to 26S proteasomes. The proteasome-associated deubiquitinating enzyme Usp14/UBP6 contains an N-terminal UBL domain and is an important regulator of proteasomal activity. Usp14 by itself represses multiple proteasomal activities but, upon binding a ubiquitin chain, Usp14 stimulates these activities and promotes ubiquitin-conjugate degradation. Here, we demonstrate that Usp14's UBL domain alone mimics this activation of proteasomes by ubiquitin chains. Addition of this UBL domain to purified 26S proteasomes stimulated the same activities inhibited by Usp14: peptide entry and hydrolysis, protein-dependent ATP hydrolysis, deubiquitination by Rpn11, and the degradation of ubiquitinated and nonubiquitinated proteins. Thus, the binding of Usp14's UBL (apparently to Rpn1's T2 site) seems to mediate the activation of proteasomes by ubiquitinated substrates. However, the stimulation of these various activities was greater in proteasomes lacking Usp14 than in wild-type particles and thus is a general response that does not involve some displacement of Usp14. Furthermore, the UBL domains from hHR23 and hPLIC1/UBQLN1 also stimulated peptide hydrolysis, and the expression of hHR23A's UBL domain in HeLa cells stimulated overall protein degradation. Therefore, many UBL-containing proteins that bind to proteasomes may also enhance allosterically its proteolytic activity.}, } @article {pmid30486898, year = {2018}, author = {Woldeamanuel, GG and Geta, TG}, title = {Prevalence of color vision deficiency among school children in Wolkite, Southern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {838}, pmid = {30486898}, issn = {1756-0500}, abstract = {OBJECTIVE: Colour vision deficiency is the commonest disorders of vision and undiagnosed colour vision defect could pose a handicap to the performance of an affected student. The prevalence of colour blindness varies in different geographical area and ethnicity. Hence, a cross sectional study was conducted among school children in Gurage Zone, Southern Ethiopia from April 15 to June 20, 2018. Socio-demographic data was collected on a face to face interview using structured questionnaire. All study participants underwent color vision evaluation using Ishihara's pseudo isochromatic test 38 plate editions. Data analysis was done using SPSS version 23.

RESULTS: A total of 844 (471 boys and 373 girls) school children were screened for colour vision. The overall prevalence of colour vision deficiency was 4.1%, comprised of 3.6% in boys and 0.6% in girls. Out of 35 color blind subjects, 15 (42.9%) and 20 (57.1%) were the victims of protan and deutan defects respectively. Majority of the colour blind subjects were not aware of their colour vision status. Hence, the study concluded that the prevalence of colour vision deficiency in our study is significant and colour vision screening among school should be performed.}, } @article {pmid30486891, year = {2018}, author = {Kassa, A and Yohannes, Z}, title = {Women's knowledge and associated factors on preconception care at Public Health Institution in Hawassa City, South Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {841}, pmid = {30486891}, issn = {1756-0500}, abstract = {OBJECTIVE: Preconception care is pivotal to improve pregnancy and birth outcome. It is vital for the future health of mother, her child and her family, which is routinely practice. The study aims to assess knowledge of preconception care and associated factors in post natal women at public health institution in Hawassa city, South Ethiopia.

RESULTS: In this study 20% (95% CI 16.9, 23.1) of post natal women at public health institution had a good level of knowledge on preconception care. Women who have secondary and above education level, urban residence, and have at least one ANC contact had significantly higher odds of good level of knowledge on preconception care. The finding of this study showed that level of women's knowledge towards preconception care to be low compared to other studies. Having at least one ANC contact, urban residence and having secondary and above education are predictors of knowledge on preconception care. It shall be beneficial if the city health administration, regional and national health authorities work towards improving the knowledge of mothers towards preconception care as well as routine provision of preconception care in the health care system.}, } @article {pmid30486872, year = {2018}, author = {Abebe, AM and Kassaw, MW and Shewangashaw, NE}, title = {Prevalence of needle-stick and sharp object injuries and its associated factors among staff nurses in Dessie referral hospital Amhara region, Ethiopia, 2018.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {840}, pmid = {30486872}, issn = {1756-0500}, abstract = {OBJECTIVE: The aim of this study was to assess the prevalence of needle-stick and sharp object injuries among staff nurses in Dessie referral hospital, Amhara region, Ethiopia, 2018.

RESULTS: Among the 151 study participants, 98 (65%) respondents were males. Seventy-five (48.1%) participants had 4-10 years of experience. The overall prevalence of needle stick and sharp object injury among staff nurses in Dessie referral hospital was 43%. In this study, nurses who worked in the emergency department were 11× more likely to experience needle stick and sharp object injury compared with nurses who worked in outpatient department P = 0.004 [AOR = 11.511 95% CI 2.134, 62.09)]. Participants who were worked in adult health department were 10× more likely experience needle stick and sharp object injury when compared with participants who were worked in outpatient department P = 0.006 [AOR = 9.742 95% CI 1.904, 49.859)]. The major implication of these study findings on the health system is the importance of given emphasis for nurses in relation with needle stick and sharp injury.}, } @article {pmid30486860, year = {2018}, author = {Atlason, RS and Giacalone, D}, title = {Rapid computation and visualization of data from Kano surveys in R.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {839}, doi = {10.1186/s13104-018-3945-x}, pmid = {30486860}, issn = {1756-0500}, abstract = {OBJECTIVE: The Kano model for user satisfaction is a popular survey-based method used by product designers to prioritize the inclusion and implementation of product features based on users' requirements. Despite its overall simplicity, a current drawback of the Kano approach is that the data analysis and processing of users' responses is laborsome and rather prone to human error. To address this drawback, this paper provides and presents a complete code to conduct a rapid yet comprehensive computation and visualization of Kano data in R.

RESULTS: A detailed walkthrough of the code is provided, together with a sample dataset to demonstrate its functionality. The code is encapsulated on a simple function that can substantially decrease the time for evaluating Kano results, speeding up its application in the context of product development.}, } @article {pmid30486859, year = {2018}, author = {Mohamed, SOO and Elkhidir, IHE and Abuzied, AIH and Noureddin, AAMH and Ibrahim, GAA and Mahmoud, AAA}, title = {Prevalence of autoimmune thyroid diseases among the Turner Syndrome patients: meta-analysis of cross sectional studies.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {842}, pmid = {30486859}, issn = {1756-0500}, abstract = {OBJECTIVE: This meta-analysis was done to estimate the prevalence of autoimmune thyroid diseases (ATDs) in Turner Syndrome patients, and to determine the clinical status of thyroid autoimmune diseases that occur frequently in association with Turner Syndrome.

RESULTS: A total of 18 studies were included in the meta-analysis. The pooled overall prevalence of autoimmune thyroid diseases in Turner Syndrome patients was 38.6% (95% CI 29.7-47.6%), with 12.7% (95% CI 9.30-16.1%) of them had clinical hypothyroidism and 2.6% (95% CI 1.5-3.8%) had hyperthyroidism. I-squared test had a high result of heterogeneity. In subgroup analyses, the prevalence of ATDs was higher in the European region than Asian region. Autoimmune thyroid diseases are commonly associated with Turner Syndrome. Early detection of thyroid diseases by optimal screening among children with Turner Syndrome is required to ensure effective management.}, } @article {pmid30486809, year = {2018}, author = {Mölter, J and Avitan, L and Goodhill, GJ}, title = {Detecting neural assemblies in calcium imaging data.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {143}, pmid = {30486809}, issn = {1741-7007}, abstract = {BACKGROUND: Activity in populations of neurons often takes the form of assemblies, where specific groups of neurons tend to activate at the same time. However, in calcium imaging data, reliably identifying these assemblies is a challenging problem, and the relative performance of different assembly-detection algorithms is unknown.

RESULTS: To test the performance of several recently proposed assembly-detection algorithms, we first generated large surrogate datasets of calcium imaging data with predefined assembly structures and characterised the ability of the algorithms to recover known assemblies. The algorithms we tested are based on independent component analysis (ICA), principal component analysis (Promax), similarity analysis (CORE), singular value decomposition (SVD), graph theory (SGC), and frequent item set mining (FIM-X). When applied to the simulated data and tested against parameters such as array size, number of assemblies, assembly size and overlap, and signal strength, the SGC and ICA algorithms and a modified form of the Promax algorithm performed well, while PCA-Promax and FIM-X did less well, for instance, showing a strong dependence on the size of the neural array. Notably, we identified additional analyses that can improve their importance. Next, we applied the same algorithms to a dataset of activity in the zebrafish optic tectum evoked by simple visual stimuli, and found that the SGC algorithm recovered assemblies closest to the averaged responses.

CONCLUSIONS: Our findings suggest that the neural assemblies recovered from calcium imaging data can vary considerably with the choice of algorithm, but that some algorithms reliably perform better than others. This suggests that previous results using these algorithms may need to be reevaluated in this light.}, } @article {pmid30486796, year = {2018}, author = {Gibbons, J and Button-Simons, KA and Adapa, SR and Li, S and Pietsch, M and Zhang, M and Liao, X and Adams, JH and Ferdig, MT and Jiang, RHY}, title = {Altered expression of K13 disrupts DNA replication and repair in Plasmodium falciparum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {849}, pmid = {30486796}, issn = {1471-2164}, support = {R01 AI117017/AI/NIAID NIH HHS/United States ; R01AI117017//National Institutes of Health/ ; USF New Investigator Funding//University of South Florida/ ; }, abstract = {BACKGROUND: Plasmodium falciparum exhibits resistance to the artemisinin component of the frontline antimalarial treatment Artemisinin-based Combination Therapy in South East Asia. Millions of lives will be at risk if artemisinin resistance (ART-R) spreads to Africa. Single non-synonymous mutations in the propeller region of PF3D7_1343700,"K13" are implicated in resistance. In this work, we use transcriptional profiling to characterize a laboratory-generated k13 insertional mutant previously demonstrated to have increased sensitivity to artemisinins to explore the functional role of k13.

RESULTS: A set of RNA-seq and microarray experiments confirmed that the expression profile of k13 is specifically altered during the early ring and early trophozoite stages of the mutant intraerythrocytic development cycle. The down-regulation of k13 transcripts in this mutant during the early ring stage is associated with a transcriptome advance towards a more trophozoite-like state. To discover the specific downstream effect of k13 dysregulation, we developed a new computational method to search for differential gene expression while accounting for the temporal sequence of transcription. We found that the strongest biological signature of the transcriptome shift is an up-regulation of DNA replication and repair genes during the early ring developmental stage and a down-regulation of DNA replication and repair genes during the early trophozoite stage; by contrast, the expressions of housekeeping genes are unchanged. This effect, due to k13 dysregulation, is antagonistic, such that k13 levels are negatively correlated with DNA replication and repair gene expression.

CONCLUSION: Our results support a role for k13 as a stress response regulator consistent with the hypothesis that artemisinins mode of action is oxidative stress and k13 as a functional homolog of Keap1 which in humans regulates DNA replication and repair genes in response to oxidative stress.}, } @article {pmid30486794, year = {2018}, author = {Javvadi, SG and Cescutti, P and Rizzo, R and Lonzarich, V and Navarini, L and Licastro, D and Guarnaccia, C and Venturi, V}, title = {The spent culture supernatant of Pseudomonas syringae contains azelaic acid.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {199}, pmid = {30486794}, issn = {1471-2180}, abstract = {BACKGROUND: Pseudomonas syringae pv. actinidiae (PSA) is an emerging kiwifruit bacterial pathogen which since 2008 has caused considerable losses. No quorum sensing (QS) signaling molecule has yet been reported from PSA and the aim of this study was to identify possible intercellular signals produced by PSA.

RESULTS: A secreted metabolome analysis resulted in the identification of 83 putative compounds, one of them was the nine carbon saturated dicarboxylic acid called azelaic acid. Azelaic acid, which is a nine-carbon (C9) saturated dicarboxylic acid, has been reported in plants as a mobile signal that primes systemic defenses. In addition, its structure,(which is associated with fatty acid biosynthesis) is similar to other known bacterial QS signals like the Diffusible Signal Facor (DSF). For these reason it could be acting as s signal molecule. Analytical and structural studies by NMR spectroscopy confirmed that in PSA spent supernatants azelaic acid was present. Quantification studies further revealed that 20 μg/L of were present and was also found in the spent supernatants of several other P. syringae pathovars. The RNAseq transcriptome study however did not determine whether azelaic acid could behave as a QS molecule.

CONCLUSIONS: This study reports of the possible natural biosynthesis of azelaic acid by bacteria. The production of azelaic acid by P. syringae pathovars can be associated with plant-bacteria signaling.}, } @article {pmid30486793, year = {2018}, author = {Aleem, B and Rashid, MH and Zeb, N and Saqib, A and Ihsan, A and Iqbal, M and Ali, H}, title = {Random mutagenesis of super Koji (Aspergillus oryzae): improvement in production and thermal stability of α-amylases for maltose syrup production.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {200}, pmid = {30486793}, issn = {1471-2180}, abstract = {BACKGROUND: Alpha-amylases hydrolyze 1,4 α-glycosidic bonds of starch and produce malto-oligosaccharides. It is an important enzyme generally applied in textile, food and brewing industries. Enhancement in thermal stability and productivity of enzymes are the two most sought after properties for industrial use. The Aspergillus oryzae (Koji) has Generally Recognized as Safe (GRAS) status and safe for use in food industry. Hence, Koji strain's development for the screening of potent mutants, hyper producer of thermostable α-amylases, with desired attributes is the need of the time.

RESULTS: A process has been developed to improve super Koji (A. oryzae cmc1) strain through γ-rays treatment. The doses i.e. 0.60, 0.80, 1.00, 1.20 & 1.40 KGy gave more than 3.0 log kill. Initially, 52 Koji mutants resistant to 1% (w/v) Triton X-100 were selected. 2nd screening was based on α-amylases hyper production and 23 mutants were sorted out by measuring clearing zones index (CI). Afterwards nine potent mutants, resistant to 2-deoxy D-glucose, were screened based on CI. These were further analyzed for thermal stability and productivity of α-amylase under submerged conditions. The mutants' M-80(10), M-100(6) & M-120(5) gave about four fold increases in α-amylases productivity. The half life of M-100(6) α-amylase at 55 °C was 52 min and was highest among the mutants. Liquid Chromatography-Mass Spectrometry (LC-MS) analysis confirmed that mutants did not produce aflatoxins. Field Emission Scanning Electron Microscopy (FESEM) of Koji mycelia depicted that exposure to gamma rays increased rigidity of the mycelium. The potent Koji mutant M-100(6) was grown on soluble starch in 10L fermenter and produced 40.0 IU ml-1 of α-amylases with specific activity of 2461 IU mg-1 protein. Growth kinetic parameters were: μ = Specific growth rate= 0.069 h-1, td = Biomass doubling time= 10.0 h, Yp/x = Product yield coefficient with respect to cell mass = 482 U g-1; qp= Specific rate of product formation= 33.29 U g-1 h-1.

CONCLUSION: It was concluded that the developed five step screening process has great potential to generate potent mutants for the hyper production of thermostable enzymes through γ-rays mediated physical mutagenesis. The developed thermostable α-amylases of super Koji mutantM-100(6) has immense potential for application in saccharification process for maltose syrup production. Moreover, the developed five step strain's development process may be used for the simultaneous improvement in productivity and thermal stability of other microbial enzymes.}, } @article {pmid30486792, year = {2018}, author = {Darrin Hulsey, C and Zheng, J and Holzman, R and Alfaro, ME and Olave, M and Meyer, A}, title = {Phylogenomics of a putatively convergent novelty: did hypertrophied lips evolve once or repeatedly in Lake Malawi cichlid fishes?.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {179}, pmid = {30486792}, issn = {1471-2148}, mesh = {Animals ; Cichlids/*classification/*genetics ; DNA, Mitochondrial/genetics ; Hybridization, Genetic ; *Lakes ; Lip/*anatomy & histology ; Malawi ; Phenotype ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: Phylogenies provide critical information about convergence during adaptive radiation. To test whether there have been multiple origins of a distinctive trophic phenotype in one of the most rapidly radiating groups known, we used ultra-conserved elements (UCEs) to examine the evolutionary affinities of Lake Malawi cichlids lineages exhibiting greatly hypertrophied lips.

RESULTS: The hypertrophied lip cichlids Cheilochromis euchilus, Eclectochromis ornatus, Placidochromis "Mbenji fatlip", and Placidochromis milomo are all nested within the non-mbuna clade of Malawi cichlids based on both concatenated sequence and single nucleotide polymorphism (SNP) inferred phylogenies. Lichnochromis acuticeps that exhibits slightly hypertrophied lips also appears to have evolutionary affinities to this group. However, Chilotilapia rhoadesii that lacks hypertrophied lips was recovered as nested within the species Cheilochromis euchilus. Species tree reconstructions and analyses of introgression provided largely ambiguous patterns of Malawi cichlid evolution.

CONCLUSIONS: Contrary to mitochondrial DNA phylogenies, bifurcating trees based on our 1024 UCE loci supported close affinities of Lake Malawi lineages with hypertrophied lips. However, incomplete lineage sorting in Malawi tends to render these inferences more tenuous. Phylogenomic analyses will continue to provide powerful inferences about whether phenotypic novelties arose once or multiple times during adaptive radiation.}, } @article {pmid30486791, year = {2018}, author = {Dressaire, C and Pobre, V and Laguerre, S and Girbal, L and Arraiano, CM and Cocaign-Bousquet, M}, title = {PNPase is involved in the coordination of mRNA degradation and expression in stationary phase cells of Escherichia coli.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {848}, pmid = {30486791}, issn = {1471-2164}, support = {SFRH/BPD/65528/2009//FCT Post-Doctoral Fellowships/ ; SFRH/BPD/87188/2012//FCT Post-Doctoral Fellowships/ ; LISBOA-01-0145-FEDER-007660//Fundação para a Ciência e Tecnologia (FCT-Portugal)/ ; No 635536//European Union's Horizon 2020 research and innovation program/ ; PTDC/BIA-MIC/1399/2014//FEDER funds/ ; }, abstract = {BACKGROUND: Exoribonucleases are crucial for RNA degradation in Escherichia coli but the roles of RNase R and PNPase and their potential overlap in stationary phase are not well characterized. Here, we used a genome-wide approach to determine how RNase R and PNPase affect the mRNA half-lives in the stationary phase. The genome-wide mRNA half-lives were determined by a dynamic analysis of transcriptomes after transcription arrest. We have combined the analysis of mRNA half-lives with the steady-state concentrations (transcriptome) to provide an integrated overview of the in vivo activity of these exoribonucleases at the genome-scale.

RESULTS: The values of mRNA half-lives demonstrated that the mRNAs are very stable in the stationary phase and that the deletion of RNase R or PNPase caused only a limited mRNA stabilization. Intriguingly the absence of PNPase provoked also the destabilization of many mRNAs. These changes in mRNA half-lives in the PNPase deletion strain were associated with a massive reorganization of mRNA levels and also variation in several ncRNA concentrations. Finally, the in vivo activity of the degradation machinery was found frequently saturated by mRNAs in the PNPase mutant unlike in the RNase R mutant, suggesting that the degradation activity is limited by the deletion of PNPase but not by the deletion of RNase R.

CONCLUSIONS: This work had identified PNPase as a central player associated with mRNA degradation in stationary phase.}, } @article {pmid30486787, year = {2018}, author = {Carlson, J and Li, JZ and Zöllner, S}, title = {Helmsman: fast and efficient mutation signature analysis for massive sequencing datasets.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {845}, pmid = {30486787}, issn = {1471-2164}, support = {R01 GM118928/GM/NIGMS NIH HHS/United States ; R01GM118928//National Institutes of Health/ ; }, abstract = {BACKGROUND: The spectrum of somatic single-nucleotide variants in cancer genomes often reflects the signatures of multiple distinct mutational processes, which can provide clinically actionable insights into cancer etiology. Existing software tools for identifying and evaluating these mutational signatures do not scale to analyze large datasets containing thousands of individuals or millions of variants.

RESULTS: We introduce Helmsman, a program designed to perform mutation signature analysis on arbitrarily large sequencing datasets. Helmsman is up to 300 times faster than existing software. Helmsman's memory usage is independent of the number of variants, resulting in a small enough memory footprint to analyze datasets that would otherwise exceed the memory limitations of other programs.

CONCLUSIONS: Helmsman is a computationally efficient tool that enables users to evaluate mutational signatures in massive sequencing datasets that are otherwise intractable with existing software. Helmsman is freely available at https://github.com/carjed/helmsman .}, } @article {pmid30486783, year = {2018}, author = {Lu, H and Cui, X and Liu, Z and Liu, Y and Wang, X and Zhou, Z and Cai, X and Zhang, Z and Guo, X and Hua, J and Ma, Z and Wang, X and Zhang, J and Zhang, H and Liu, F and Wang, K}, title = {Discovery and annotation of a novel transposable element family in Gossypium.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {307}, pmid = {30486783}, issn = {1471-2229}, support = {31530053//National Natural Science Foundation of China/ ; 2016YFD0100203//National Key Research and Development Plan/ ; 2016YFD0101401//National Key Research and Development Plan/ ; }, mesh = {Chromosomes, Artificial, Bacterial/genetics ; Chromosomes, Plant/genetics ; DNA Transposable Elements/*genetics ; Genome, Plant/genetics ; Gossypium/*genetics ; In Situ Hybridization, Fluorescence ; Sequence Analysis, DNA ; Tetraploidy ; }, abstract = {BACKGROUND: Fluorescence in situ hybridization (FISH) is an efficient cytogenetic technology to study chromosome structure. Transposable element (TE) is an important component in eukaryotic genomes and can provide insights in the structure and evolution of eukaryotic genomes.

RESULTS: A FISH probe derived from bacterial artificial chromosome (BAC) clone 299N22 generated striking signals on all 26 chromosomes of the cotton diploid A genome (AA, 2x=26) but very few on the diploid D genome (DD, 2x=26). All 26 chromosomes of the A sub genome (At) of tetraploid cotton (AADD, 2n=4x=52) also gave positive signals with this FISH probe, whereas very few signals were observed on the D sub genome (Dt). Sequencing and annotation of BAC clone 299N22, revealed a novel Ty3/gypsy transposon family, which was named as 'CICR'. This family is a significant contributor to size expansion in the A (sub) genome but not in the D (sub) genome. Further FISH analysis with the LTR of CICR as a probe revealed that CICR is lineage-specific, since massive repeats were found in A and B genomic groups, but not in C-G genomic groups within the Gossypium genus. Molecular evolutionary analysis of CICR suggested that tetraploid cottons evolved after silence of the transposon family 1-1.5 million years ago (Mya). Furthermore, A genomes are more homologous with B genomes, and the C, E, F, and G genomes likely diverged from a common ancestor prior to 3.5-4 Mya, the time when CICR appeared. The genomic variation caused by the insertion of CICR in the A (sub) genome may have played an important role in the speciation of organisms with A genomes.

CONCLUSIONS: The CICR family is highly repetitive in A and B genomes of Gossypium, but not amplified in the C-G genomes. The differential amount of CICR family in At and Dt will aid in partitioning sub genome sequences for chromosome assemblies during tetraploid genome sequencing and will act as a method for assessing the accuracy of tetraploid genomes by looking at the proportion of CICR elements in resulting pseudochromosome sequences. The timeline of the expansion of CICR family provides a new reference for cotton evolutionary analysis, while the impact on gene function caused by the insertion of CICR elements will be a target for further analysis of investigating phenotypic differences between A genome and D genome species.}, } @article {pmid30486782, year = {2018}, author = {Baichoo, S and Souilmi, Y and Panji, S and Botha, G and Meintjes, A and Hazelhurst, S and Bendou, H and Beste, E and Mpangase, PT and Souiai, O and Alghali, M and Yi, L and O'Connor, BD and Crusoe, M and Armstrong, D and Aron, S and Joubert, F and Ahmed, AE and Mbiyavanga, M and Heusden, PV and Magosi, LE and Zermeno, J and Mainzer, LS and Fadlelmola, FM and Jongeneel, CV and Mulder, N}, title = {Developing reproducible bioinformatics analysis workflows for heterogeneous computing environments to support African genomics.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {457}, pmid = {30486782}, issn = {1471-2105}, support = {U41 HG006941/HG/NHGRI NIH HHS/United States ; U41HG006941//National Human Genome Research Institute/ ; }, mesh = {Africa ; Computational Biology/*methods ; Genomics/*methods ; Humans ; Reproducibility of Results ; }, abstract = {BACKGROUND: The Pan-African bioinformatics network, H3ABioNet, comprises 27 research institutions in 17 African countries. H3ABioNet is part of the Human Health and Heredity in Africa program (H3Africa), an African-led research consortium funded by the US National Institutes of Health and the UK Wellcome Trust, aimed at using genomics to study and improve the health of Africans. A key role of H3ABioNet is to support H3Africa projects by building bioinformatics infrastructure such as portable and reproducible bioinformatics workflows for use on heterogeneous African computing environments. Processing and analysis of genomic data is an example of a big data application requiring complex interdependent data analysis workflows. Such bioinformatics workflows take the primary and secondary input data through several computationally-intensive processing steps using different software packages, where some of the outputs form inputs for other steps. Implementing scalable, reproducible, portable and easy-to-use workflows is particularly challenging.

RESULTS: H3ABioNet has built four workflows to support (1) the calling of variants from high-throughput sequencing data; (2) the analysis of microbial populations from 16S rDNA sequence data; (3) genotyping and genome-wide association studies; and (4) single nucleotide polymorphism imputation. A week-long hackathon was organized in August 2016 with participants from six African bioinformatics groups, and US and European collaborators. Two of the workflows are built using the Common Workflow Language framework (CWL) and two using Nextflow. All the workflows are containerized for improved portability and reproducibility using Docker, and are publicly available for use by members of the H3Africa consortium and the international research community.

CONCLUSION: The H3ABioNet workflows have been implemented in view of offering ease of use for the end user and high levels of reproducibility and portability, all while following modern state of the art bioinformatics data processing protocols. The H3ABioNet workflows will service the H3Africa consortium projects and are currently in use. All four workflows are also publicly available for research scientists worldwide to use and adapt for their respective needs. The H3ABioNet workflows will help develop bioinformatics capacity and assist genomics research within Africa and serve to increase the scientific output of H3Africa and its Pan-African Bioinformatics Network.}, } @article {pmid30486781, year = {2018}, author = {Hecox-Lea, BJ and Mark Welch, DB}, title = {Evolutionary diversity and novelty of DNA repair genes in asexual Bdelloid rotifers.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {177}, pmid = {30486781}, issn = {1471-2148}, support = {R21 AG046899/AG/NIA NIH HHS/United States ; R21AG046899/AG/NIA NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Conserved Sequence/genetics ; DNA Repair/*genetics ; *Evolution, Molecular ; Gene Dosage ; Gene Transfer, Horizontal/genetics ; *Genetic Variation ; Phylogeny ; Proteins/chemistry/genetics ; Reproduction, Asexual/*genetics ; Rotifera/*genetics ; }, abstract = {BACKGROUND: Bdelloid rotifers are the oldest, most diverse and successful animal taxon for which males, hermaphrodites, and traditional meiosis are unknown. Their degenerate tetraploid genome, with 2-4 copies of most loci, includes thousands of genes acquired from all domains of life by horizontal transfer. Many bdelloid species thrive in ephemerally aquatic habitats by surviving desiccation at any life stage with no loss of fecundity or lifespan. Their unique genomic diversity and the intense selective pressure of desiccation provide an exceptional opportunity to study the evolution of diversity and novelty in genes involved in DNA repair.

RESULTS: We used genomic data and RNA-Seq of the desiccation process in the bdelloid Adineta vaga to characterize DNA damage reversal, translesion synthesis, and the major DNA repair pathways: base, nucleotide, and alternate excision repair, mismatch repair (MMR), and double strand break repair by homologous recombination (HR) and classical non-homologous end joining (NHEJ). We identify multiple horizontally transferred DNA damage response genes otherwise unknown in animals (AlkD, Fpg, LigK UVDE), and the presence of genes often considered vertebrate specific, particularly in the NHEJ complex and X family polymerases. While 75-100% of genes involved in MMR and HR are present in 0-2 copies, genes involved in NHEJ, which are present in only a single copy in nearly all other animals, are retained in 3-8 copies. We present structural predictions and expression evidence of neo- or sub-functionalization of multiple copy genes involved in NHEJ and other repair processes.

CONCLUSION: The horizontally-acquired genes and duplicated genes in BER and NHEJ suggest resilience to oxidative damage is conferred in part by increased DNA damage recognition and efficient end repair capabilities. The pattern of gene loss and retention in MMR and HR may facilitate recombination and gene conversion between divergent sequences, thus providing at least some of the benefits of sex. The unique retention and divergence of duplicates genes in NHEJ may be facilitated by the lack of efficient selection in the absence of meiotic recombination and independent assortment, and may contribute to the evolutionary success of bdelloids.}, } @article {pmid30486780, year = {2018}, author = {Fletcher, K and Klosterman, SJ and Derevnina, L and Martin, F and Bertier, LD and Koike, S and Reyes-Chin-Wo, S and Mou, B and Michelmore, R}, title = {Comparative genomics of downy mildews reveals potential adaptations to biotrophy.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {851}, pmid = {30486780}, issn = {1471-2164}, support = {P30 CA093373/CA/NCI NIH HHS/United States ; S10 OD018223/OD/NIH HHS/United States ; S10 RR026825/RR/NCRR NIH HHS/United States ; Endowed Chair in Genomics//Novozymes Inc./ ; C06 RR012088/RR/NCRR NIH HHS/United States ; }, abstract = {BACKGROUND: Spinach downy mildew caused by the oomycete Peronospora effusa is a significant burden on the expanding spinach production industry, especially for organic farms where synthetic fungicides cannot be deployed to control the pathogen. P. effusa is highly variable and 15 new races have been recognized in the past 30 years.

RESULTS: We virulence phenotyped, sequenced, and assembled two isolates of P. effusa from the Salinas Valley, California, U.S.A. that were identified as race 13 and 14. These assemblies are high quality in comparison to assemblies of other downy mildews having low total scaffold count (784 & 880), high contig N50s (48 kb & 52 kb), high BUSCO completion and low BUSCO duplication scores and share many syntenic blocks with Phytophthora species. Comparative analysis of four downy mildew and three Phytophthora species revealed parallel absences of genes encoding conserved domains linked to transporters, pathogenesis, and carbohydrate activity in the biotrophic species. Downy mildews surveyed that have lost the ability to produce zoospores have a common loss of flagella/motor and calcium domain encoding genes. Our phylogenomic data support multiple origins of downy mildews from hemibiotrophic progenitors and suggest that common gene losses in these downy mildews may be of genes involved in the necrotrophic stages of Phytophthora spp.

CONCLUSIONS: We present a high-quality draft genome of Peronospora effusa that will serve as a reference for Peronospora spp. We identified several Pfam domains as under-represented in the downy mildews consistent with the loss of zoosporegenesis and necrotrophy. Phylogenomics provides further support for a polyphyletic origin of downy mildews.}, } @article {pmid30486779, year = {2018}, author = {Auman, T and Chipman, AD}, title = {Growth zone segmentation in the milkweed bug Oncopeltus fasciatus sheds light on the evolution of insect segmentation.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {178}, pmid = {30486779}, issn = {1471-2148}, mesh = {Animals ; Asclepias/*parasitology ; *Biological Evolution ; *Body Patterning/genetics ; Drosophila/genetics ; Gene Expression Regulation, Developmental ; Genes, Insect ; Heteroptera/*genetics ; Insect Proteins/genetics/metabolism ; Phenotype ; RNA Interference ; RNA, Messenger/genetics/metabolism ; }, abstract = {BACKGROUND: One of the best studied developmental processes is the Drosophila segmentation cascade. However, this cascade is generally considered to be highly derived and unusual, with segments being patterned simultaneously, rather than the ancestral sequential segmentation mode. We present a detailed analysis of the segmentation cascade of the milkweed bug Oncopletus fasciatus, an insect with a more primitive segmentation mode, as a comparison to Drosophila, with the aim of reconstructing the evolution of insect segmentation modes.

RESULTS: We document the expression of 12 genes, representing different phases in the segmentation process. Using double staining we reconstruct the spatio-temporal relationships among these genes. We then show knock-down phenotypes of representative genes in order to uncover their roles and position in the cascade.

CONCLUSIONS: We conclude that sequential segmentation in the Oncopeltus germband includes three slightly overlapping phases: Primary pair-rule genes generate the first segmental gene expression in the anterior growth zone. This pattern is carried anteriorly by a series of secondary pair-rule genes, expressed in the transition between the growth zone and the segmented germband. Segment polarity genes are expressed in the segmented germband with conserved relationships. Unlike most holometabolous insects, this process generates a single-segment periodicity, and does not have a double-segment pattern at any stage. We suggest that the evolutionary transition to double-segment patterning lies in mutually exclusive expression patterns of secondary pair-rule genes. The fact that many aspects of the putative Oncopeltus segmentation network are similar to those of Drosophila, is consistent with a simple transition between sequential and simultaneous segmentation.}, } @article {pmid30486778, year = {2018}, author = {Liu, W and Cheng, C and Chen, F and Ni, S and Lin, Y and Lai, Z}, title = {High-throughput sequencing of small RNAs revealed the diversified cold-responsive pathways during cold stress in the wild banana (Musa itinerans).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {308}, pmid = {30486778}, issn = {1471-2229}, support = {CARS-32-11//the earmarked Fund for China Agriculture Research System/ ; 31601713//the National Natural Science Foundation of China/ ; }, mesh = {Circadian Rhythm/genetics/physiology ; Cold Temperature/adverse effects ; Cold-Shock Response/genetics ; Genes, Plant/genetics/physiology ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics/physiology ; Musa/*genetics/metabolism/physiology ; Signal Transduction/*genetics/physiology ; Transcription Factors/genetics/physiology ; }, abstract = {BACKGROUND: Cold stress is one of the most severe abiotic stresses affecting the banana production. Although some miRNAs have been identified, little is known about the role of miRNAs in response to cold stress in banana, and up to date, there is no report about the role of miRNAs in the response to cold stress in the plants of the cultivated or wild bananas.

RESULT: Here, a cold-resistant line wild banana (Musa itinerans) from China was used to profile the cold-responsive miRNAs by RNA-seq during cold stress. Totally, 265 known mature miRNAs and 41 novel miRNAs were obtained. Cluster analysis of differentially expressed (DE) miRNAs indicated that some miRNAs were specific for chilling or 0 °C treated responses, and most of them were reported to be cold-responsive; however, some were seldom reported to be cold-responsive in response to cold stress, e.g., miR395, miR408, miR172, suggesting that they maybe play key roles in response to cold stress. The GO and KEGG pathway enrichment analysis of DE miRNAs targets indicated that there existed diversified cold-responsive pathways, and miR172 was found likely to play a central coordinating role in response to cold stress, especially in the regulation of CK2 and the circadian rhythm. Finally, qPCR assays indicated the related targets were negatively regulated by the tested DE miRNAs during cold stress in the wild banana.

CONCLUSIONS: In this study, the profiling of miRNAs by RNA-seq in response to cold stress in the plants of the wild banana (Musa itinerans) was reported for the first time. The results showed that there existed diversified cold-responsive pathways, which provided insight into the roles of miRNAs during cold stress, and would be helpful for alleviating cold stress and cold-resistant breeding in bananas.}, } @article {pmid30486776, year = {2018}, author = {Niu, L and Pan, L and Zeng, W and Lu, Z and Cui, G and Fan, M and Xu, Q and Wang, Z and Li, G}, title = {Dynamic transcriptomes of resistant and susceptible peach lines after infestation by green peach aphids (Myzus persicae Sülzer) reveal defence responses controlled by the Rm3 locus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {846}, pmid = {30486776}, issn = {1471-2164}, support = {CAAS-ASTIP-2018-ZFRI//the Agricultural Science and Technology Innovation Program/ ; 31701880//the National Natural Science Foundation of China/ ; 1610192017703//the Central Public-interest Scientific Institution Basal Research Fund/ ; }, abstract = {BACKGROUND: The green peach aphid (GPA), Myzus persicae (Sülzer), is a widespread phloem-feeding insect that significantly influences the yield and visual quality of peach [Prunus persica (L.) Batsch]. Single dominant gene (Rm3)-based resistance provides effective management of this invasive pest, although little is known about the molecular responses of plants to GPA feeding.

RESULTS: To illustrate the molecular mechanisms of monogenic resistance in peach to young tissue-infecting GPAs, aphid-resistant/aphid-susceptible peach lines from a segregating population with Rm3/rm3 and rm3/rm3 genotypes were infested with GPAs for 3 to 72 h. Transcriptome analysis of the infested tissues identified 3854 differentially expressed genes (DEGs). Although the majority of the DEGs in the resistant line also responded to aphid attack in the susceptible line, the overall magnitude of change was greater in the resistant line than in the susceptible line. The enriched gene ontology of the 3854 DEGs involved in plant defence responses included redox situation, calcium-mediated signalling, transcription factor (e.g., WRKY, MYB, and ERF), MAPK signalling cascade, phytohormone signalling, pathogenesis-related protein, and secondary metabolite terms. Of the 53 genes annotated in a 460 kb interval of the rm3 locus, seven genes were differentially expressed between the aphid-resistant and aphid-susceptible peach lines following aphid infestation.

CONCLUSIONS: Together, these results suggest that the Rm3-dependent resistance relies mainly on the inducible expression of defence-related pathways and signalling elements within hours after the initiation of aphid feeding and that the production of specific secondary metabolites from phenylpropanoid/flavonoid pathways can have major effects on peach-aphid interactions.}, } @article {pmid30486775, year = {2018}, author = {Pazos, F and Garcia-Moreno, A and Oliveros, JC}, title = {Automatic detection of genomic regions with informative epigenetic patterns.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {847}, pmid = {30486775}, issn = {1471-2164}, support = {SAF2016-78041-C2-2-R//Spanish Ministry for Economy and Competitiveness/ ; }, abstract = {BACKGROUND: Epigenetic phenomena are crucial for explaining the phenotypic plasticity seen in the cells of different tissues, developmental stages and diseases, all holding the same DNA sequence. As technology is allowing to retrieve epigenetic information in a genome-wide fashion, massive epigenomic datasets are being accumulated in public repositories. New approaches are required to mine those data to extract useful knowledge. We present here an automatic approach for detecting genomic regions with epigenetic variation patterns across samples related to a grouping of these samples, as a way of detecting regions functionally associated to the phenomenon behind the classification.

RESULTS: We show that the regions automatically detected by the method in the whole human genome associated to three different classifications of a set of epigenomes (cancer vs. healthy, brain vs. other organs, and fetal vs. adult tissues) are enriched in genes associated to these processes.

CONCLUSIONS: The method is fully automatic and can exhaustively scan the whole human genome at any resolution using large collections of epigenomes as input, although it also produces good results with small datasets. Consequently, it will be valuable for obtaining functional information from the incoming epigenomic information as it continues to accumulate.}, } @article {pmid30486772, year = {2018}, author = {Phani, V and Somvanshi, VS and Shukla, RN and Davies, KG and Rao, U}, title = {A transcriptomic snapshot of early molecular communication between Pasteuria penetrans and Meloidogyne incognita.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {850}, pmid = {30486772}, issn = {1471-2164}, support = {DST 59FX34 2014//UK-India Education and Research Initiative/ ; }, abstract = {BACKGROUND: Southern root-knot nematode Meloidogyne incognita (Kofoid and White, 1919), Chitwood, 1949 is a key pest of agricultural crops. Pasteuria penetrans is a hyperparasitic bacterium capable of suppressing the nematode reproduction, and represents a typical coevolved pathogen-hyperparasite system. Attachment of Pasteuria endospores to the cuticle of second-stage nematode juveniles is the first and pivotal step in the bacterial infection. RNA-Seq was used to understand the early transcriptional response of the root-knot nematode at 8 h post Pasteuria endospore attachment.

RESULTS: A total of 52,485 transcripts were assembled from the high quality (HQ) reads, out of which 582 transcripts were found differentially expressed in the Pasteuria endospore encumbered J2 s, of which 229 were up-regulated and 353 were down-regulated. Pasteuria infection caused a suppression of the protein synthesis machinery of the nematode. Several of the differentially expressed transcripts were putatively involved in nematode innate immunity, signaling, stress responses, endospore attachment process and post-attachment behavioral modification of the juveniles. The expression profiles of fifteen selected transcripts were validated to be true by the qRT PCR. RNAi based silencing of transcripts coding for fructose bisphosphate aldolase and glucosyl transferase caused a reduction in endospore attachment as compared to the controls, whereas, silencing of aspartic protease and ubiquitin coding transcripts resulted in higher incidence of endospore attachment on the nematode cuticle.

CONCLUSIONS: Here we provide evidence of an early transcriptional response by the nematode upon infection by Pasteuria prior to root invasion. We found that adhesion of Pasteuria endospores to the cuticle induced a down-regulated protein response in the nematode. In addition, we show that fructose bisphosphate aldolase, glucosyl transferase, aspartic protease and ubiquitin coding transcripts are involved in modulating the endospore attachment on the nematode cuticle. Our results add new and significant information to the existing knowledge on early molecular interaction between M. incognita and P. penetrans.}, } @article {pmid30486770, year = {2018}, author = {Samarasinghe, SR and Samaranayake, N and Kariyawasam, UL and Siriwardana, YD and Imamura, H and Karunaweera, ND}, title = {Genomic insights into virulence mechanisms of Leishmania donovani: evidence from an atypical strain.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {843}, pmid = {30486770}, issn = {1471-2164}, support = {U01AI136033, R01AI099602//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: Leishmaniasis is a neglected tropical disease with diverse clinical phenotypes, determined by parasite, host and vector interactions. Despite the advances in molecular biology and the availability of more Leishmania genome references in recent years, the association between parasite species and distinct clinical phenotypes remains poorly understood. We present a genomic comparison of an atypical variant of Leishmania donovani from a South Asian focus, where it mostly causes cutaneous form of leishmaniasis.

RESULTS: Clinical isolates from six cutaneous leishmaniasis patients (CL-SL); 2 of whom were poor responders to antimony (CL-PR), and two visceral leishmaniasis patients (VL-SL) were sequenced on an Illumina MiSeq platform. Chromosome aneuploidy was observed in both groups but was more frequent in CL-SL. 248 genes differed by 2 fold or more in copy number among the two groups. Genes involved in amino acid use (LdBPK_271940) and energy metabolism (LdBPK_271950), predominated the VL-SL group with the same distribution pattern reflected in gene tandem arrays. Genes encoding amastins were present in higher copy numbers in VL-SL and CL-PR as well as being among predicted pseudogenes in CL-SL. Both chromosome and SNP profiles showed CL-SL and VL-SL to form two distinct groups. While expected heterozygosity was much higher in VL-SL, SNP allele frequency patterns did not suggest potential recent recombination breakpoints. The SNP/indel profile obtained using the more recently generated PacBio sequence did not vary markedly from that based on the standard LdBPK282A1 reference. Several genes previously associated with resistance to antimonials were observed in higher copy numbers in the analysis of CL-PR. H-locus amplification was seen in one cutaneous isolate which however did not belong to the CL-PR group.

CONCLUSIONS: The data presented suggests that intra species variations at chromosome and gene level are more likely to influence differences in tropism as well as response to treatment, and contributes to greater understanding of parasite molecular mechanisms underpinning these differences. These findings should be substantiated with a larger sample number and expression/functional studies.}, } @article {pmid30486769, year = {2018}, author = {Liu, Y and Jia, Y and Liu, C and Ding, L and Xia, Z}, title = {RNA-Seq transcriptome analysis of breast muscle in Pekin ducks supplemented with the dietary probiotic Clostridium butyricum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {844}, pmid = {30486769}, issn = {1471-2164}, abstract = {BACKGROUND: Increased attention is being paid to breast muscle yield and meat quality in the duck breeding industry. Our previous report has demonstrated that dietary Clostridium butyricum (C. butyricum) can improve meat quality of Pekin ducks. However, the potential biological processes and molecular mechanisms that are modulated by dietary C. butyricum in the breast muscle of Pekin ducks remain unknown.

RESULTS: Supplementation with C. butyricum increased growth performance and meat yield. Therefore, we utilized de novo assembly methods to analyze the RNA-Seq transcriptome profiles in breast muscle to explore the differentially expressed genes between C. butyricum-treated and control Pekin ducks. A total of 1119 differentially expressed candidate genes were found of which 403 genes were significantly up-regulated and 716 genes were significantly down-regulated significantly. qRT-PCR analysis was used to confirm the accuracy of the of RNA-Seq results. GO annotations revealed potential genes, processes and pathways that may participate in meat quality and muscle development. KEGG pathway analysis showed that the differentially expressed genes participated in numerous pathways related to muscle development, including ECM-receptor interaction, the MAPK signaling pathway and the TNF signaling pathway.

CONCLUSIONS: This study suggests that long-time dietary supplementation with C. butyricum can modulate muscle development and meat quality via altering the expression patterns of genes involved in crucial metabolic pathways. The findings presented here provide unique insights into the molecular mechanisms of muscle development in Pekin ducks in response to dietary C. butyricum.}, } @article {pmid30486673, year = {2018}, author = {Nussinson, R and Mentser, S and Rosenberg, N}, title = {Sensitivity to Deviance and to Dissimilarity: Basic Cognitive Processes Under Activation of the Behavioral Immune System.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918813433}, doi = {10.1177/1474704918813433}, pmid = {30486673}, issn = {1474-7049}, abstract = {Throughout evolutionary history, pathogens have imposed strong selection pressures on humans. To minimize humans' exposure to pathogens, a behavioral immune system that promotes the detection and avoidance of disease-connoting cues has evolved. Although most pathogens cannot be discerned by our sensory organs, they produce discernable changes in their environment. As a result, a common denominator of many disease-connoting cues is morphological deviance-figurative disparity from what is normal, visual dissimilarity to the prototype stored in memory. Drawing on an evolutionary rationale, we examine the hypothesis that activation of the behavioral immune system renders people more sensitive to morphological deviance and more prone to perceive dissimilarities between stimuli. In Study 1 (N = 343), participants who scored higher on disgust sensitivity demonstrated greater differentiation between normal and disfigured faces, reflecting greater sensitivity to morphological deviance in the bodily domain. In Study 2 (N = 109), participants who were primed with pathogen threat demonstrated greater differentiation between perfect and imperfect geometrical shapes, reflecting greater sensitivity to morphological deviance even in stimuli that have nothing to do with health or disease. In Study 3 (N = 621), participants who scored higher on disgust sensitivity perceived pairs of neutral pictures as less similar (i.e., more dissimilar) to each other. Literature on the relations to social deviance and implications for social perception and for social behavior is discussed.}, } @article {pmid30485755, year = {2018}, author = {Rempel, S and Stanek, WK and Slotboom, DJ}, title = {Energy-Coupling Factor-Type ATP-Binding Cassette Transporters.}, journal = {Annual review of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-biochem-013118-111705}, pmid = {30485755}, issn = {1545-4509}, abstract = {Energy-coupling factor (ECF)-type ATP-binding cassette (ABC) transporters catalyze membrane transport of micronutrients in prokaryotes. Crystal structures and biochemical characterization have revealed that ECF transporters are mechanistically distinct from other ABC transport systems. Notably, ECF transporters make use of small integral membrane subunits (S-components) that are predicted to topple over in the membrane when carrying the bound substrate from the extracellular side of the bilayer to the cytosol. Here, we review the phylogenetic diversity of ECF transporters as well as recent structural and biochemical advancements that have led to the postulation of conceptually different mechanistic models. These models can be described as power stroke and thermal ratchet. Structural data indicate that the lipid composition and bilayer structure are likely to have great impact on the transport function. We argue that study of ECF transporters could lead to generic insight of membrane protein structure, dynamics, and interaction. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30485643, year = {2018}, author = {Briand, E and Reubrecht, S and Mondeguer, F and Sibat, M and Hess, P and Amzil, Z and Bormans, M}, title = {Chemically mediated interactions between Microcystis and Planktothrix: impact on their growth, morphology and metabolic profiles.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14490}, pmid = {30485643}, issn = {1462-2920}, support = {301244-CYANOMIC//FP7 People: Marie-Curie Actions/ ; }, abstract = {Freshwater cyanobacteria are known for their ability to produce bioactive compounds, some of which have been described as allelochemicals. Using a combined approach of co-cultures and analyses of metabolic profiles, we investigated chemically mediated interactions between two cyanobacterial strains, Microcystis aeruginosa PCC 7806 and Planktothrix agardhii PCC 7805. More precisely, we evaluated changes in growth, morphology and metabolite production and release by both interacting species. Co-culture of Microcystis with Planktothrix resulted in a reduction of the growth of Planktothrix together with a decrease of its trichome size and alterations in the morphology of its cells. The production of intracellular compounds by Planktothrix showed a slight decrease between monoculture and co-culture conditions. Concerning Microcystis, the number of intracellular compounds was higher under co-culture condition than under monoculture. Overall, Microcystis produced a lower number of intracellular compounds under monoculture than Planktothrix, and a higher number of intracellular compounds than Planktothrix under co-culture condition. Our investigation did not allow us to identify specifically the compounds causing the observed physiological and morphological changes of Planktothrix cells. However, altogether, these results suggest that co-culture induces specific compounds as a response by Microcystis to the presence of Planktothrix. Further studies should be undertaken for identification of such potential allelochemicals.}, } @article {pmid30485588, year = {2018}, author = {Jacobs, RL and Baker, BW}, title = {The species dilemma and its potential impact on enforcing wildlife trade laws.}, journal = {Evolutionary anthropology}, volume = {27}, number = {6}, pages = {261-266}, doi = {10.1002/evan.21751}, pmid = {30485588}, issn = {1520-6505}, mesh = {Animals ; *Animals, Wild ; Conservation of Natural Resources ; Endangered Species/*legislation & jurisprudence ; Forensic Sciences ; Law Enforcement ; *Primates ; United States ; }, abstract = {The varied answers to the question "What is a species?" provoke more than lively debates in academic circles. They pose practical problems for law enforcement. Commercial wildlife trade threatens many primate species and is regulated through such laws and international agreements as the U.S. Endangered Species Act and the Convention on International Trade in Endangered Species of Wild Fauna and Flora. Enforcing legislation relies on the ability to identify when violations occur. Species-defining characters may not be preserved in wildlife trade items. For example, pelage patterns and behavioral characters (e.g., vocalizations) are absent from skulls. Accordingly, identifying victims of illegal trade can be difficult, which hinders enforcement. Moreover, identifying new species and "splitting" of currently recognized species can result in enforcement lags and regulatory loopholes. Although such negative consequences should not hinder scientific advancement, we suggest that they be considered by primate taxonomists and provide recommendations to prevent unintended conservation consequences.}, } @article {pmid30485577, year = {2018}, author = {Moran, PA and Hunt, J and Mitchell, C and Ritchie, MG and Bailey, NW}, title = {Behavioural mechanisms of sexual isolation involving multiple modalities and their inheritance.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13408}, pmid = {30485577}, issn = {1420-9101}, support = {NE/G014906/1//NERC/ ; NE/L011255/1//NERC/ ; NE/G00949X/1//NERC/ ; DP180101708//ARC/ ; //Orthopterists' Society/ ; }, abstract = {Speciation research dissects the genetics and evolution of reproductive barriers between parental species. Hybrids are the 'gatekeepers' of gene flow, so it is also important to understand the behavioural mechanisms and genetics of any potential isolation from their parental species. We tested the role of multiple behavioural barriers in reproductive isolation among closely related field crickets and their hybrids (Teleogryllus oceanicus and T. commodus). These species hybridize in the laboratory, but the behaviour of hybrids is unusual and there is little evidence for gene flow in the wild. We found that heterospecific pairs exhibited reduced rates of courtship behaviour due to discrimination by both sexes, and that this behavioural isolation was symmetrical. However, hybrids were not sexually selected against and exhibited high rates of courtship behaviour even though hybrid females are sterile. Using reciprocal hybrid crosses, we characterized patterns of interspecific divergence and inheritance in key sexual traits that might underlie the mating patterns we found: calling song, courtship song and cuticular hydrocarbons (CHCs). Song traits exhibited both sex linkage and transgressive segregation, whereas CHCs exhibited only the latter. Calculations of the strength of isolation exerted by these sexual traits suggest that close-range signals are as important as long-distance signals in contributing to interspecific sexual isolation. The surprisingly weak mating barriers observed between hybrids and parental species highlight the need to examine reproductive isolating mechanisms and their genetic bases across different potential stages of introgressive hybridization.}, } @article {pmid30484944, year = {2018}, author = {Lamont, BB and He, T and Yan, Z}, title = {Evolutionary history of fire-stimulated resprouting, flowering, seed release and germination.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12483}, pmid = {30484944}, issn = {1469-185X}, support = {2662016QD021//Chinese Ministry of Education/ ; DP120103389//Australian Research Council/ ; DP130103029//Australian Research Council/ ; }, abstract = {Fire has shaped the evolution of many plant traits in fire-prone environments: fire-resistant tissues with heat-insulated meristems, post-fire resprouting or fire-killed but regenerating from stored seeds, fire-stimulated flowering, release of on-plant-stored seeds, and germination of soil-stored seeds. Flowering, seed release and germination fit into three categories of response to intensifying fire: fire not required, weakly fire-adapted or strongly fire-adapted. Resprouting also has three categories but survival is always reduced by increasing fire intensity. We collated 286 records for 20 angiosperm and two gymnosperm families and 50 trait assignments to dated phylogenies. We placed these into three fire-adapted trait types: those associated with the origin of their clade and the onset of fire-proneness [primary diversification, contributing 20% of speciation events over the last 120 million years (My)], those originating much later coincident with a change in the fire regime (secondary diversification, 30%), and those conserved in the daughter lineage as already adapted to the fire regime (stabilisation, 50%). All four fire-response types could be traced to >100 My ago (Mya) with pyrogenic flowering slightly younger because of its dependence on resprouting. There was no evidence that resprouting was always an older trait than either seed storage or non-sprouting throughout this period, with either/both ancestral or derived in different clades and times. Fire-adapted traits evolved slowly in the Cretaceous, 120-65 Mya, and rapidly but fitfully in the Cenozoic, 65-0 Mya, peaking over the last 20 My. The four trait-types climaxed at different times, with the peak in resprouter speciation over the last 5 My attributable to fluctuating growing conditions and increasing savanna grasslands unsuitable for non-sprouters. All experienced a trough in the 40-30-Mya period following a reduction in world temperatures and oxygen levels and expected reduced fire activity. Thick bark and serotiny arose in the Mid-Cretaceous among extant Pinaceae. Heat-stimulated germination of hard seeds is ancestral in the 103-My-old Fabales. Smoke-(karrikin)-stimulated germination of non-hard seeds is even older, and includes the 101-My-old Restionaceae-Anarthriaceae. A smoke/karrikin response is detectable in some fire-free lineages that prove to have a fire-prone ancestry. Among clades that are predominantly fire-prone, absence of fire-related traits is the advanced condition, associated either with increased fire frequency (loss of serotiny and soil storage), or migration to fire-free habitats (loss of thick bark, pyrogenic flowering, serotiny or soil storage). Protea (Africa) and Hakea (Australia) illustrate the importance of stabilisation processes between resprouting/non-sprouting in accounting for speciation events over the last 20 My and highlight the frequent interchange possible between these two traits. Apart from Pinus, most ancestral trait reconstruction relative to fire has been conducted on predominantly Southern Hemisphere clades and this needs to be redressed. Despite these limitations, it is clear that fire has had a profound effect on fire-related trait evolution worldwide, and set the platform for subsequent evolution of many non-fire-related traits. Genetics of the triggering mechanisms remain poorly understood, except the karrikin system for smoke-stimulated germination. We exhort biologists to include fire-proneness and fire-related traits in their thinking on possible factors controlling the evolution of plants.}, } @article {pmid30484943, year = {2018}, author = {Hare, RM and Simmons, LW}, title = {Sexual selection and its evolutionary consequences in female animals.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12484}, pmid = {30484943}, issn = {1469-185X}, support = {//Australian Government Research Training Program/ ; //Australian Research Council/ ; }, abstract = {For sexual selection to act on a given sex, there must exist variation in the reproductive success of that sex as a result of differential access to mates or fertilisations. The mechanisms and consequences of sexual selection acting on male animals are well documented, but research on sexual selection acting on females has only recently received attention. Controversy still exists over whether sexual selection acts on females in the traditional sense, and over whether to modify the existing definition of sexual selection (to include resource competition) or to invoke alternative mechanisms (usually social selection) to explain selection acting on females in connection with reproduction. However, substantial evidence exists of females bearing characters or exhibiting behaviours that result in differential reproductive success that are analogous to those attributed to sexual selection in males. Here we summarise the literature and provide substantial evidence of female intrasexual competition for access to mates, female intersexual signalling to potential mates, and postcopulatory mechanisms such as competition between eggs for access to sperm and cryptic male allocation. Our review makes clear that sexual selection acts on females and males in similar ways but sometimes to differing extents: the ceiling for the elaboration of costly traits may be lower in females than in males. We predict that current and future research on female sexual selection will provide increasing support for the parsimony and utility of the existing definition of sexual selection.}, } @article {pmid30484924, year = {2018}, author = {Alpern, JHM and Asselin, MM and Moehring, AJ}, title = {Identification of a novel sperm class and its role in fertilization in Drosophila.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13409}, pmid = {30484924}, issn = {1420-9101}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {In many species, males have evolved to produce a sterile sperm (parasperm) in conjunction with fertilizing sperm (eusperm). Here, we document evidence of males depositing two morphologically distinct types of parasperm (1 and 2) into the female reproductive tract in Drosophila pseudoobscura. These parasperm differ in length, shape, amount produced, amount in long-term storage and may have separate roles in ensuring male fertilization success. Although both parasperm types protect eusperm from female spermicides, only parasperm 2, which has a corkscrew shape, is associated with sperm competition. Increased production of parasperm 2 is also negatively correlated with the eusperm and parasperm 1 production. Thus, selection may be acting on parasperm production in the presence of sperm competition. Our findings show how both sperm competition and cryptic female choice may be acting in conjunction to influence the evolution of ejaculate composition. Our identification and characterization of two distinct parasperm morphs will enhance the ability for further evaluation of parasperm's role in fertilization.}, } @article {pmid30484761, year = {2019}, author = {Ellis, JC and Thomas, MS and Lawson, PA and Patel, NB and Faircloth, W and Hayes, SE and Linton, EE and Norden, DM and Severenchuk, IS and West, CH and Brown, JW and Plante, RG and Plante, CJ}, title = {Kistimonas alittae sp. nov., a gammaproteobacterium isolated from the marine annelid Alitta succinea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {235-240}, doi = {10.1099/ijsem.0.003137}, pmid = {30484761}, issn = {1466-5034}, abstract = {A novel Gram-stain-negative, rod-shaped, motile, non-spore-forming, facultatively anaerobic marine bacterium was isolated from the gastrointestinal tract of the sandworm Alitta succinea collected from Grice Cove, South Carolina, USA. The strain was arginine dihydrolase-positive, and oxidase- and catalase-positive. Growth occurred between 10 and 37 °C, with optimal growth occurring between 30 and 32 °C. Comparative 16S rRNA gene sequence analysis showed its nearest neighbours are members of the genus Kistimonas of the family Hahellaceae, which is found in the order Oceanospirillales, class Gammaproteobacteria. The closest related species was Kistimonas asteriae KMD 001T with 16S rRNA gene sequence similarity of 99.0 %. However, DNA-DNA hybridization between these strains revealed less than 70 % DNA-DNA relatedness, supporting the novel species status of the strain. The major fatty acids were C16 : 0, C18 : 0, C18 : 1ω7c and a summed feature that contained C16 : 1ω6c/C16 : 1ω7c. The major respiratory quinone was ubiquinone-9 and the predominant polar lipids were phosphatidylserine, phosphoethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The genomic DNA G+C content was 52.5 mol%. Based on the data presented, strain BGP-2T is considered to represent a novel member of the genus Kistimonas, for which the name Kistimonas alittae sp. nov. is proposed. The type strain is BGP-2T (=CCUG 65711T=JCM 30010T).}, } @article {pmid30484760, year = {2019}, author = {Chang, YQ and Meng, X and Du, ZZ and Du, ZJ}, title = {Oceanibium sediminis gen. nov., sp. nov., isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {249-254}, doi = {10.1099/ijsem.0.003139}, pmid = {30484760}, issn = {1466-5034}, abstract = {A novel Gram-stain-negative, rod-shaped marine bacterium, designated as strain O448T, was isolated from the coastal area of Weihai, China (122° 14' E, 36° 54' N). Cells of strain O448T were non-motile, aerobic, approximately 0.4-0.6 µm wide and 1.5-2.0 µm long. Growth occurred at 20-40 °C (optimally between 33-37 °C), pH 6.5-8.0 (optimally at 7.0) and in the presence of 1.0-5.0 % (w/v) NaCl (optimally between 2.0-3.0 %). Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain O448T belongs to family Rhodobacteraceae and exhibits 16S rRNA gene sequence similarities of 94.3, 94.1 and 93.8 % to the type strains of Pontivivens insulae, Halovulum dunhuangense and Maritimibacter alkaliphilus, respectively. The major cellular fatty acid was C18 : 1ω7c and the major polar lipids were phosphatidylethanolamine, phosphatidylcholine and phosphatidylglycerol. Strain O448T contained Q-10 as the sole respiratory quinone. The genomic DNA G+C content was 65.6 mol%. It is evident from phenotypic data and phylogenetic inference that strain O448T represents a novel species in a new genus, for which the name Oceanibiumsediminis gen. nov., sp. nov. is proposed. The type strain is O448T (=KCTC 62076T=MCCC 1H00233T).}, } @article {pmid30483871, year = {2018}, author = {Ely, B and Wilson, K and Ross, K and Ingram, D and Lewter, T and Herring, J and Duncan, D and Aikins, A and Scott, D}, title = {Genome Comparisons of Wild Isolates of Caulobacter crescentus Reveal Rates of Inversion and Horizontal Gene Transfer.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1606-x}, pmid = {30483871}, issn = {1432-0991}, support = {R25 GM066526/GM/NIGMS NIH HHS/United States ; R25 GM076277/GM/NIGMS NIH HHS/United States ; GM076277//National Institute of General Medical Sciences/ ; P20GM103446//National Institute of General Medical Sciences/ ; }, abstract = {Since previous interspecies comparisons of Caulobacter genomes have revealed extensive genome rearrangements, we decided to compare the nucleotide sequences of four C. crescentus genomes, NA1000, CB1, CB2, and CB13. To accomplish this goal, we used PacBio sequencing technology to determine the nucleotide sequence of the CB1, CB2, and CB13 genomes, and obtained each genome sequence as a single contig. To correct for possible sequencing errors, each genome was sequenced twice. The only differences we observed between the two sets of independently determined sequences were random omissions of a single base in a small percentage of the homopolymer regions where a single base is repeated multiple times. Comparisons of these four genomes indicated that horizontal gene transfer events that included small numbers of genes occurred at frequencies in the range of 10-3 to 10-4 insertions per generation. Large insertions were about 100 times less frequent. Also, in contrast to previous interspecies comparisons, we found no genome rearrangements when the closely related NA1000, CB1, and CB2 genomes were compared, and only eight inversions and one translocation when the more distantly related CB13 genome was compared to the other genomes. Thus, we estimate that inversions occur at a rate of one per 10 to 12 million generations in Caulobacter genomes. The inversions seem to be complex events that include the simultaneous creation of indels.}, } @article {pmid30482938, year = {2018}, author = {Abeysekara, AU and Albert, A and Alfaro, R and Alvarez, C and Álvarez, JD and Arceo, R and Arteaga-Velázquez, JC and Avila Rojas, D and Ayala Solares, HA and Belmont-Moreno, E and BenZvi, SY and Brisbois, C and Caballero-Mora, KS and Capistrán, T and Carramiñana, A and Casanova, S and Castillo, M and Cotti, U and Cotzomi, J and Coutiño de León, S and De León, C and De la Fuente, E and Díaz-Vélez, JC and Dichiara, S and Dingus, BL and DuVernois, MA and Ellsworth, RW and Engel, K and Espinoza, C and Fang, K and Fleischhack, H and Fraija, N and Galván-Gámez, A and García-González, JA and Garfias, F and González-Muñoz, A and González, MM and Goodman, JA and Hampel-Arias, Z and Harding, JP and Hernandez, S and Hinton, J and Hona, B and Hueyotl-Zahuantitla, F and Hui, CM and Hüntemeyer, P and Iriarte, A and Jardin-Blicq, A and Joshi, V and Kaufmann, S and Kar, P and Kunde, GJ and Lauer, RJ and Lee, WH and León Vargas, H and Li, H and Linnemann, JT and Longinotti, AL and Luis-Raya, G and López-Coto, R and Malone, K and Marinelli, SS and Martinez, O and Martinez-Castellanos, I and Martínez-Castro, J and Matthews, JA and Miranda-Romagnoli, P and Moreno, E and Mostafá, M and Nayerhoda, A and Nellen, L and Newbold, M and Nisa, MU and Noriega-Papaqui, R and Pretz, J and Pérez-Pérez, EG and Ren, Z and Rho, CD and Rivière, C and Rosa-González, D and Rosenberg, M and Ruiz-Velasco, E and Salesa Greus, F and Sandoval, A and Schneider, M and Schoorlemmer, H and Seglar Arroyo, M and Sinnis, G and Smith, AJ and Springer, RW and Surajbali, P and Taboada, I and Tibolla, O and Tollefson, K and Torres, I and Vianello, G and Villaseñor, L and Weisgarber, T and Werner, F and Westerhoff, S and Wood, J and Yapici, T and Yodh, G and Zepeda, A and Zhang, H and Zhou, H}, title = {Publisher Correction: Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {E38}, doi = {10.1038/s41586-018-0688-8}, pmid = {30482938}, issn = {1476-4687}, abstract = {In this Letter, owing to a production error, the penultimate version of the PDF was published. The HTML version was always correct. The PDF has been corrected online.}, } @article {pmid30482931, year = {2018}, author = {Senn, S}, title = {Statistical pitfalls of personalized medicine.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {619-621}, doi = {10.1038/d41586-018-07535-2}, pmid = {30482931}, issn = {1476-4687}, } @article {pmid30482930, year = {2018}, author = {Else, H}, title = {Can a major AI conference shed its reputation for hosting sexist behaviour?.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {610-611}, doi = {10.1038/d41586-018-07552-1}, pmid = {30482930}, issn = {1476-4687}, } @article {pmid30482929, year = {2018}, author = {Cyranoski, D and Ledford, H}, title = {Genome-edited baby claim provokes international outcry.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {607-608}, doi = {10.1038/d41586-018-07545-0}, pmid = {30482929}, issn = {1476-4687}, } @article {pmid30482928, year = {2018}, author = {Reardon, S}, title = {Frustrated Alzheimer's researchers seek better lab mice.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {611-612}, doi = {10.1038/d41586-018-07484-w}, pmid = {30482928}, issn = {1476-4687}, } @article {pmid30482927, year = {2018}, author = {Heaven, D}, title = {AI peer reviewers unleashed to ease publishing grind.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {609-610}, doi = {10.1038/d41586-018-07245-9}, pmid = {30482927}, issn = {1476-4687}, } @article {pmid30482926, year = {2018}, author = {}, title = {The party drug that helps to patch over betrayal.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {603}, doi = {10.1038/d41586-018-07491-x}, pmid = {30482926}, issn = {1476-4687}, } @article {pmid30482925, year = {2018}, author = {Witze, A}, title = {'Marsquake' hunter prepares to land on the red planet.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {608-609}, doi = {10.1038/d41586-018-07482-y}, pmid = {30482925}, issn = {1476-4687}, } @article {pmid30482924, year = {2018}, author = {}, title = {A nation where millions barely move.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {603}, doi = {10.1038/d41586-018-07473-z}, pmid = {30482924}, issn = {1476-4687}, } @article {pmid30482923, year = {2018}, author = {Gilmore, MS and Miller, OK}, title = {A bacterium's enemy isn't your friend.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {637-638}, doi = {10.1038/d41586-018-07414-w}, pmid = {30482923}, issn = {1476-4687}, mesh = {Cell Wall ; Glycosylation ; *Methicillin ; *Methicillin-Resistant Staphylococcus aureus ; }, } @article {pmid30482922, year = {2018}, author = {}, title = {A synthetic flower that unfolds in the dark.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {602}, doi = {10.1038/d41586-018-07469-9}, pmid = {30482922}, issn = {1476-4687}, } @article {pmid30482921, year = {2018}, author = {}, title = {A switch by China's home cooks helps to save millions of lives.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {602}, doi = {10.1038/d41586-018-07470-2}, pmid = {30482921}, issn = {1476-4687}, } @article {pmid30482920, year = {2018}, author = {}, title = {A simple gadget nudges people to save energy in the shower.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {603}, doi = {10.1038/d41586-018-07471-1}, pmid = {30482920}, issn = {1476-4687}, } @article {pmid30482919, year = {2018}, author = {}, title = {Termite mounds dating back millennia can be seen from space.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {603}, doi = {10.1038/d41586-018-07459-x}, pmid = {30482919}, issn = {1476-4687}, } @article {pmid30482918, year = {2018}, author = {}, title = {Skull-collecting ants slay with acid.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {602}, doi = {10.1038/d41586-018-07458-y}, pmid = {30482918}, issn = {1476-4687}, } @article {pmid30482877, year = {2018}, author = {Woo, M}, title = {Inner Workings: Mapping the microbiome location helps elucidate its role.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12078-12080}, pmid = {30482877}, issn = {1091-6490}, } @article {pmid30482864, year = {2018}, author = {Langelier, C and Kalantar, KL and Moazed, F and Wilson, MR and Crawford, ED and Deiss, T and Belzer, A and Bolourchi, S and Caldera, S and Fung, M and Jauregui, A and Malcolm, K and Lyden, A and Khan, L and Vessel, K and Quan, J and Zinter, M and Chiu, CY and Chow, ED and Wilson, J and Miller, S and Matthay, MA and Pollard, KS and Christenson, S and Calfee, CS and DeRisi, JL}, title = {Integrating host response and unbiased microbe detection for lower respiratory tract infection diagnosis in critically ill adults.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {E12353-E12362}, doi = {10.1073/pnas.1809700115}, pmid = {30482864}, issn = {1091-6490}, abstract = {Lower respiratory tract infections (LRTIs) lead to more deaths each year than any other infectious disease category. Despite this, etiologic LRTI pathogens are infrequently identified due to limitations of existing microbiologic tests. In critically ill patients, noninfectious inflammatory syndromes resembling LRTIs further complicate diagnosis. To address the need for improved LRTI diagnostics, we performed metagenomic next-generation sequencing (mNGS) on tracheal aspirates from 92 adults with acute respiratory failure and simultaneously assessed pathogens, the airway microbiome, and the host transcriptome. To differentiate pathogens from respiratory commensals, we developed a rules-based model (RBM) and logistic regression model (LRM) in a derivation cohort of 20 patients with LRTIs or noninfectious acute respiratory illnesses. When tested in an independent validation cohort of 24 patients, both models achieved accuracies of 95.5%. We next developed pathogen, microbiome diversity, and host gene expression metrics to identify LRTI-positive patients and differentiate them from critically ill controls with noninfectious acute respiratory illnesses. When tested in the validation cohort, the pathogen metric performed with an area under the receiver-operating curve (AUC) of 0.96 (95% CI, 0.86-1.00), the diversity metric with an AUC of 0.80 (95% CI, 0.63-0.98), and the host transcriptional classifier with an AUC of 0.88 (95% CI, 0.75-1.00). Combining these achieved a negative predictive value of 100%. This study suggests that a single streamlined protocol offering an integrated genomic portrait of pathogen, microbiome, and host transcriptome may hold promise as a tool for LRTI diagnosis.}, } @article {pmid30482863, year = {2018}, author = {Belda-Palazon, B and Gonzalez-Garcia, MP and Lozano-Juste, J and Coego, A and Antoni, R and Julian, J and Peirats-Llobet, M and Rodriguez, L and Berbel, A and Dietrich, D and Fernandez, MA and Madueño, F and Bennett, MJ and Rodriguez, PL}, title = {PYL8 mediates ABA perception in the root through non-cell-autonomous and ligand-stabilization-based mechanisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11857-E11863}, doi = {10.1073/pnas.1815410115}, pmid = {30482863}, issn = {1091-6490}, support = {BB/M002136/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The phytohormone abscisic acid (ABA) plays a key role regulating root growth, root system architecture, and root adaptive responses, such as hydrotropism. The molecular and cellular mechanisms that regulate the action of core ABA signaling components in roots are not fully understood. ABA is perceived through receptors from the PYR/PYL/RCAR family and PP2C coreceptors. PYL8/RCAR3 plays a nonredundant role in regulating primary and lateral root growth. Here we demonstrate that ABA specifically stabilizes PYL8 compared with other ABA receptors and induces accumulation of PYL8 in root nuclei. This requires ABA perception by PYL8 and leads to diminished ubiquitination of PYL8 in roots. The ABA agonist quinabactin, which promotes root ABA signaling through dimeric receptors, fails to stabilize the monomeric receptor PYL8. Moreover, a PYL8 mutant unable to bind ABA and inhibit PP2C is not stabilized by the ligand, whereas a PYL85KR mutant is more stable than PYL8 at endogenous ABA concentrations. The PYL8 transcript was detected in the epidermis and stele of the root meristem; however, the PYL8 protein was also detected in adjacent tissues. Expression of PYL8 driven by tissue-specific promoters revealed movement to adjacent tissues. Hence both inter- and intracellular trafficking of PYL8 appears to occur in the root apical meristem. Our findings reveal a non-cell-autonomous mechanism for hormone receptors and help explain the nonredundant role of PYL8-mediated root ABA signaling.}, } @article {pmid30482862, year = {2018}, author = {Sharma, S and Lindau, M}, title = {Molecular mechanism of fusion pore formation driven by the neuronal SNARE complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12751-12756}, doi = {10.1073/pnas.1816495115}, pmid = {30482862}, issn = {1091-6490}, mesh = {Cytoplasm/metabolism ; Diaphragm/metabolism ; Hydrophobic and Hydrophilic Interactions ; Membrane Fusion/*physiology ; Membrane Proteins/metabolism ; Models, Structural ; Mutant Proteins/metabolism ; Neurons/*metabolism ; Neurotransmitter Agents/metabolism ; Protein Domains ; SNARE Proteins/*metabolism ; Synaptic Vesicles/metabolism ; Syntaxin 1/metabolism ; Vesicle-Associated Membrane Protein 2/metabolism ; }, abstract = {Release of neurotransmitters from synaptic vesicles begins with a narrow fusion pore, the structure of which remains unresolved. To obtain a structural model of the fusion pore, we performed coarse-grained molecular dynamics simulations of fusion between a nanodisc and a planar bilayer bridged by four partially unzipped SNARE complexes. The simulations revealed that zipping of SNARE complexes pulls the polar C-terminal residues of the synaptobrevin 2 and syntaxin 1A transmembrane domains to form a hydrophilic core between the two distal leaflets, inducing fusion pore formation. The estimated conductances of these fusion pores are in good agreement with experimental values. Two SNARE protein mutants inhibiting fusion experimentally produced no fusion pore formation. In simulations in which the nanodisc was replaced by a 40-nm vesicle, an extended hemifusion diaphragm formed but a fusion pore did not, indicating that restricted SNARE mobility is required for rapid fusion pore formation. Accordingly, rapid fusion pore formation also occurred in the 40-nm vesicle system when SNARE mobility was restricted by external forces. Removal of the restriction is required for fusion pore expansion.}, } @article {pmid30482861, year = {2018}, author = {Guerrero, RF and Hahn, MW}, title = {Quantifying the risk of hemiplasy in phylogenetic inference.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12787-12792}, doi = {10.1073/pnas.1811268115}, pmid = {30482861}, issn = {1091-6490}, mesh = {Animals ; Evolution, Molecular ; Genome/*genetics ; Models, Genetic ; *Phylogeny ; Primates ; Probability ; Risk Factors ; }, abstract = {Convergent evolution-the appearance of the same character state in apparently unrelated organisms-is often inferred when a trait is incongruent with the species tree. However, trait incongruence can also arise from changes that occur on discordant gene trees, a process referred to as hemiplasy. Hemiplasy is rarely taken into account in studies of convergent evolution, despite the fact that phylogenomic studies have revealed rampant discordance. Here, we study the relative probabilities of homoplasy (including convergence and reversal) and hemiplasy for an incongruent trait. We derive expressions for the probabilities of the two events, showing that they depend on many of the same parameters. We find that hemiplasy is as likely-or more likely-than homoplasy for a wide range of conditions, even when levels of discordance are low. We also present a method to calculate the ratio of these two probabilities (the "hemiplasy risk factor") along the branches of a phylogeny of arbitrary length. Such calculations can be applied to any tree to identify when and where incongruent traits may be due to hemiplasy.}, } @article {pmid30482860, year = {2018}, author = {Clarke, AM and Engel, KL and Giles, KE and Petit, CM and Schneider, DA}, title = {NETSeq reveals heterogeneous nucleotide incorporation by RNA polymerase I.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11633-E11641}, doi = {10.1073/pnas.1809421115}, pmid = {30482860}, issn = {1091-6490}, support = {R01 AI134693/AI/NIAID NIH HHS/United States ; R01 GM084946/GM/NIGMS NIH HHS/United States ; }, abstract = {DNA sequence motifs that affect RNA polymerase transcription elongation are well studied in prokaryotic organisms and contribute directly to regulation of gene expression. Despite significant work on the regulation of eukaryotic transcription, the effect of DNA template sequence on RNA polymerase I (Pol I) transcription elongation remains unknown. In this study, we examined the effects of DNA sequence motifs on Pol I transcription elongation kinetics in vitro and in vivo. Specifically, we characterized how the spy rho-independent terminator motif from Escherichia coli directly affects Saccharomyces cerevisiae Pol I activity, demonstrating evolutionary conservation of sequence-specific effects on transcription. The insight gained from this analysis led to the identification of a homologous sequence in the ribosomal DNA of S. cerevisiae We then used native elongating transcript sequencing (NETSeq) to determine whether Pol I encounters pause-inducing sequences in vivo. We found hundreds of positions within the ribosomal DNA (rDNA) that reproducibly induce pausing in vivo. We also observed significantly lower Pol I occupancy at G residues in the rDNA, independent of other sequence context, indicating differential nucleotide incorporation rates for Pol I in vivo. These data demonstrate that DNA template sequence elements directly influence Pol I transcription elongation. Furthermore, we have developed the necessary experimental and analytical methods to investigate these perturbations in living cells going forward.}, } @article {pmid30482859, year = {2018}, author = {Chen, GH and Liu, MJ and Xiong, Y and Sheen, J and Wu, SH}, title = {TOR and RPS6 transmit light signals to enhance protein translation in deetiolating Arabidopsis seedlings.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12823-12828}, doi = {10.1073/pnas.1809526115}, pmid = {30482859}, issn = {1091-6490}, mesh = {Arabidopsis/*metabolism/*physiology ; Arabidopsis Proteins/*metabolism ; Cotyledon/metabolism ; Cryptochromes/metabolism ; Etiolation/*physiology ; Gene Expression Regulation, Plant/physiology ; Indoleacetic Acids/metabolism ; Light ; Phosphatidylinositol 3-Kinases/*metabolism ; Phosphorylation/physiology ; Photoreceptors, Plant/metabolism ; Photosynthesis/physiology ; Phytochrome A/metabolism ; Plant Growth Regulators/metabolism ; Protein Biosynthesis/*physiology ; Seedlings/*metabolism/physiology ; Signal Transduction/physiology ; Transcriptome/physiology ; }, abstract = {Deetiolation is an essential developmental process transforming young plant seedlings into the vegetative phase with photosynthetic activities. Light signals initiate this important developmental process by triggering massive reprogramming of the transcriptome and translatome. Compared with the wealth of knowledge of transcriptional regulation, the molecular mechanism underlying this light-triggered translational enhancement remains unclear. Here we show that light-enhanced translation is orchestrated by a light perception and signaling pathway composed of photoreceptors, CONSTITUTIVE PHOTOMORPHOGENESIS 1 (COP1), the phytohormone auxin, target of rapamycin (TOR), and ribosomal protein S6 (RPS6). In deetiolating Arabidopsis seedlings, photoreceptors, including phytochrome A and cryptochromes, perceive far-red and blue light to inactivate the negative regulator COP1, which leads to activation of the auxin pathway for TOR-dependent phosphorylation of RPS6. Arabidopsis mutants defective in TOR, RPS6A, or RPS6B exhibited delayed cotyledon opening, a characteristic of the deetiolating process to ensure timely vegetative development of a young seedling. This study provides a mechanistic view of light-triggered translational enhancement in deetiolating Arabidopsis.}, } @article {pmid30482858, year = {2018}, author = {Ayyildiz, M and Scaraggi, M and Sirin, O and Basdogan, C and Persson, BNJ}, title = {Contact mechanics between the human finger and a touchscreen under electroadhesion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12668-12673}, doi = {10.1073/pnas.1811750115}, pmid = {30482858}, issn = {1091-6490}, abstract = {The understanding and control of human skin contact against technological substrates is the key aspect behind the design of several electromechanical devices. Among these, surface haptic displays that modulate the friction between the human finger and touch surface are emerging as user interfaces. One such modulation can be achieved by applying an alternating voltage to the conducting layer of a capacitive touchscreen to control electroadhesion between its surface and the finger pad. However, the nature of the contact interactions between the fingertip and the touchscreen under electroadhesion and the effects of confined material properties, such as layering and inelastic deformation of the stratum corneum, on the friction force are not completely understood yet. Here, we use a mean field theory based on multiscale contact mechanics to investigate the effect of electroadhesion on sliding friction and the dependency of the finger-touchscreen interaction on the applied voltage and other physical parameters. We present experimental results on how the friction between a finger and a touchscreen depends on the electrostatic attraction between them. The proposed model is successfully validated against full-scale (but computationally demanding) contact mechanics simulations and the experimental data. Our study shows that electroadhesion causes an increase in the real contact area at the microscopic level, leading to an increase in the electrovibrating tangential frictional force. We find that it should be possible to further augment the friction force, and thus the human tactile sensing, by using a thinner insulating film on the touchscreen than used in current devices.}, } @article {pmid30482857, year = {2018}, author = {Tsunekawa, N and Ogawa, H and Tsueda, J and Akiba, T and Toyoshima, C}, title = {Mechanism of the E2 to E1 transition in Ca2+ pump revealed by crystal structures of gating residue mutants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12722-12727}, doi = {10.1073/pnas.1815472115}, pmid = {30482857}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/chemistry ; Calcium/*chemistry ; Crystallography, X-Ray ; Cytoplasm/chemistry ; Hydrolysis ; Protein Domains ; Protons ; Sarcoplasmic Reticulum/chemistry ; Sarcoplasmic Reticulum Calcium-Transporting ATPases/*chemistry ; }, abstract = {Ca2+-ATPase of sarcoplasmic reticulum (SERCA1a) pumps two Ca2+ per ATP hydrolyzed from the cytoplasm and two or three protons in the opposite direction. In the E2 state, after transferring Ca2+ into the lumen of sarcoplasmic reticulum, all of the acidic residues that coordinate Ca2+ are thought to be protonated, including the gating residue Glu309. Therefore a Glu309Gln substitution is not expected to significantly perturb the structure. Here we report crystal structures of the Glu309Gln and Glu309Ala mutants of SERCA1a under E2 conditions. The Glu309Gln mutant exhibits, unexpectedly, large structural rearrangements in both the cytoplasmic and transmembrane domains, apparently uncoupling them. However, the structure definitely represents E2 and, together with the help of quantum chemical calculations, allows us to postulate a mechanism for the E2 → E1 transition triggered by deprotonation of Glu309.}, } @article {pmid30482856, year = {2018}, author = {Ocko, SA and Hardcastle, K and Giocomo, LM and Ganguli, S}, title = {Emergent elasticity in the neural code for space.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11798-E11806}, doi = {10.1073/pnas.1805959115}, pmid = {30482856}, issn = {1091-6490}, support = {R01 MH106475/MH/NIMH NIH HHS/United States ; }, abstract = {Upon encountering a novel environment, an animal must construct a consistent environmental map, as well as an internal estimate of its position within that map, by combining information from two distinct sources: self-motion cues and sensory landmark cues. How do known aspects of neural circuit dynamics and synaptic plasticity conspire to accomplish this feat? Here we show analytically how a neural attractor model that combines path integration of self-motion cues with Hebbian plasticity in synaptic weights from landmark cells can self-organize a consistent map of space as the animal explores an environment. Intriguingly, the emergence of this map can be understood as an elastic relaxation process between landmark cells mediated by the attractor network. Moreover, our model makes several experimentally testable predictions, including (i) systematic path-dependent shifts in the firing fields of grid cells toward the most recently encountered landmark, even in a fully learned environment; (ii) systematic deformations in the firing fields of grid cells in irregular environments, akin to elastic deformations of solids forced into irregular containers; and (iii) the creation of topological defects in grid cell firing patterns through specific environmental manipulations. Taken together, our results conceptually link known aspects of neurons and synapses to an emergent solution of a fundamental computational problem in navigation, while providing a unified account of disparate experimental observations.}, } @article {pmid30482855, year = {2018}, author = {Bidkhori, G and Benfeitas, R and Klevstig, M and Zhang, C and Nielsen, J and Uhlen, M and Boren, J and Mardinoglu, A}, title = {Metabolic network-based stratification of hepatocellular carcinoma reveals three distinct tumor subtypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11874-E11883}, doi = {10.1073/pnas.1807305115}, pmid = {30482855}, issn = {1091-6490}, abstract = {Hepatocellular carcinoma (HCC) is one of the most frequent forms of liver cancer, and effective treatment methods are limited due to tumor heterogeneity. There is a great need for comprehensive approaches to stratify HCC patients, gain biological insights into subtypes, and ultimately identify effective therapeutic targets. We stratified HCC patients and characterized each subtype using transcriptomics data, genome-scale metabolic networks and network topology/controllability analysis. This comprehensive systems-level analysis identified three distinct subtypes with substantial differences in metabolic and signaling pathways reflecting at genomic, transcriptomic, and proteomic levels. These subtypes showed large differences in clinical survival associated with altered kynurenine metabolism, WNT/β-catenin-associated lipid metabolism, and PI3K/AKT/mTOR signaling. Integrative analyses indicated that the three subtypes rely on alternative enzymes (e.g., ACSS1/ACSS2/ACSS3, PKM/PKLR, ALDOB/ALDOA, MTHFD1L/MTHFD2/MTHFD1) to catalyze the same reactions. Based on systems-level analysis, we identified 8 to 28 subtype-specific genes with pivotal roles in controlling the metabolic network and predicted that these genes may be targeted for development of treatment strategies for HCC subtypes by performing in silico analysis. To validate our predictions, we performed experiments using HepG2 cells under normoxic and hypoxic conditions and observed opposite expression patterns between genes expressed in high/moderate/low-survival tumor groups in response to hypoxia, reflecting activated hypoxic behavior in patients with poor survival. In conclusion, our analyses showed that the heterogeneous HCC tumors can be stratified using a metabolic network-driven approach, which may also be applied to other cancer types, and this stratification may have clinical implications to drive the development of precision medicine.}, } @article {pmid30482854, year = {2018}, author = {Nonomura, K and Lukacs, V and Sweet, DT and Goddard, LM and Kanie, A and Whitwam, T and Ranade, SS and Fujimori, T and Kahn, ML and Patapoutian, A}, title = {Mechanically activated ion channel PIEZO1 is required for lymphatic valve formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12817-12822}, doi = {10.1073/pnas.1817070115}, pmid = {30482854}, issn = {1091-6490}, support = {R01 HL120872/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Actomyosin/metabolism ; Animals ; Antigens, CD/metabolism ; Cadherins/metabolism ; Cell Adhesion/physiology ; Cell Movement/physiology ; Endothelial Cells/metabolism/physiology ; Forkhead Transcription Factors/metabolism ; Intercellular Junctions/metabolism/physiology ; Ion Channels/*metabolism ; Ion Transport/physiology ; Lymphangiogenesis/*physiology ; Lymphatic System/*metabolism/*physiology ; Lymphatic Vessels/*metabolism/*physiology ; Mice ; NFATC Transcription Factors/metabolism ; Signal Transduction/physiology ; Transcription Factors/metabolism ; }, abstract = {PIEZO1 is a cation channel that is activated by mechanical forces such as fluid shear stress or membrane stretch. PIEZO1 loss-of-function mutations in patients are associated with congenital lymphedema with pleural effusion. However, the mechanistic link between PIEZO1 function and the development or function of the lymphatic system is currently unknown. Here, we analyzed two mouse lines lacking PIEZO1 in endothelial cells (via Tie2Cre or Lyve1Cre) and found that they exhibited pleural effusion and died postnatally. Strikingly, the number of lymphatic valves was dramatically reduced in these mice. Lymphatic valves are essential for ensuring proper circulation of lymph. Mechanical forces have been implicated in the development of lymphatic vasculature and valve formation, but the identity of mechanosensors involved is unknown. Expression of FOXC2 and NFATc1, transcription factors known to be required for lymphatic valve development, appeared normal in Tie2Cre;Piezo1cKO mice. However, the process of protrusion in the valve leaflets, which is associated with collective cell migration, actin polymerization, and remodeling of cell-cell junctions, was impaired in Tie2Cre;Piezo1cKO mice. Consistent with these genetic findings, activation of PIEZO1 by Yoda1 in cultured lymphatic endothelial cells induced active remodeling of actomyosin and VE-cadherin+ cell-cell adhesion sites. Our analysis provides evidence that mechanically activated ion channel PIEZO1 is a key regulator of lymphatic valve formation.}, } @article {pmid30482245, year = {2018}, author = {Silverman, JD and Durand, HK and Bloom, RJ and Mukherjee, S and David, LA}, title = {Correction to: Dynamic linear models guide design and analysis of microbiota studies within artificial human guts.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {212}, pmid = {30482245}, issn = {2049-2618}, abstract = {AbstractFollowing publication of the original article [1], the authors noticed an error in the presentation of equations in the PDF version.}, } @article {pmid30482244, year = {2018}, author = {Wolde, F and Mulaw, Z and Zena, T and Biadgo, B and Limenih, MA}, title = {Determinants of late initiation for antenatal care follow up: the case of northern Ethiopian pregnant women.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {837}, pmid = {30482244}, issn = {1756-0500}, abstract = {OBJECTIVE: Early antenatal care follow-up is the main strategy of preventing pregnancy related adverse outcomes; in which World Health Organization recommends first antenatal care visit should be offered within the first trimester. However, Low utilization and late booking is the predominant problem in most developing countries including Ethiopia. This study aimed to determine the prevalence of late initiation for antenatal care follow-up and associated factors among pregnant women. Institutional based cross-sectional study was conducted among 423 pregnant mothers using systematic sampling technique. Multivariable logistic regression analysis was performed at the level of significance of p-value ≤ 0.05.

RESULTS: The findings showed 59.4% of pregnant women started their first visit after first trimester. Having age ≥ 25 years (AOR = 1.62, CI 1.1, 2.49), recognition of pregnancy by missed period (AOR = 2.54 CI 1.63, 3.96), pregnant mother who were not advised to start antenatal-care (AOR = 3.36, CI 1.74, 6.5) and primary educational level (AOR = 2.22, CI 1.16, 4.25) were found to be significantly associated with late initiation for antenatal care. The prevalence of late antenatal care follow-up is high. Multidisciplinary approaches to keep empowering women through education are recommended for early initiation of antenatal care.}, } @article {pmid30482240, year = {2018}, author = {Huang, P and Zhang, Y and Xiao, K and Jiang, F and Wang, H and Tang, D and Liu, D and Liu, B and Liu, Y and He, X and Liu, H and Liu, X and Qing, Z and Liu, C and Huang, J and Ren, Y and Yun, L and Yin, L and Lin, Q and Zeng, C and Su, X and Yuan, J and Lin, L and Hu, N and Cao, H and Huang, S and Guo, Y and Fan, W and Zeng, J}, title = {The chicken gut metagenome and the modulatory effects of plant-derived benzylisoquinoline alkaloids.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {211}, pmid = {30482240}, issn = {2049-2618}, support = {2017YFD0501500//National Key R&D Program of China/ ; 2016YFD0501308//National Key R&D Program of China/ ; 2016YFC1200600//National Key R&D Program of China/ ; JCYJ20150630165133395//Shenzhen Science and Technology Program/ ; ZDSYS20141118170111640//Fund of Key Laboratory of Shenzhen/ ; }, abstract = {BACKGROUND: Sub-therapeutic antibiotics are widely used as growth promoters in the poultry industry; however, the resulting antibiotic resistance threatens public health. A plant-derived growth promoter, Macleaya cordata extract (MCE), with effective ingredients of benzylisoquinoline alkaloids, is a potential alternative to antibiotic growth promoters. Altered intestinal microbiota play important roles in growth promotion, but the underlying mechanism remains unknown.

RESULTS: We generated 1.64 terabases of metagenomic data from 495 chicken intestinal digesta samples and constructed a comprehensive chicken gut microbial gene catalog (9.04 million genes), which is also the first gene catalog of an animal's gut microbiome that covers all intestinal compartments. Then, we identified the distinctive characteristics and temporal changes in the foregut and hindgut microbiota. Next, we assessed the impact of MCE on chickens and gut microbiota. Chickens fed with MCE had improved growth performance, and major microbial changes were confined to the foregut, with the predominant role of Lactobacillus being enhanced, and the amino acids, vitamins, and secondary bile acids biosynthesis pathways being upregulated, but lacked the accumulation of antibiotic-resistance genes. In comparison, treatment with chlortetracycline similarly enriched some biosynthesis pathways of nutrients in the foregut microbiota, but elicited an increase in antibiotic-producing bacteria and antibiotic-resistance genes.

CONCLUSION: The reference gene catalog of the chicken gut microbiome is an important supplement to animal gut metagenomes. Metagenomic analysis provides insights into the growth-promoting mechanism of MCE, and underscored the importance of utilizing safe and effective growth promoters.}, } @article {pmid30482201, year = {2018}, author = {Cenci, U and Sibbald, SJ and Curtis, BA and Kamikawa, R and Eme, L and Moog, D and Henrissat, B and Maréchal, E and Chabi, M and Djemiel, C and Roger, AJ and Kim, E and Archibald, JM}, title = {Nuclear genome sequence of the plastid-lacking cryptomonad Goniomonas avonlea provides insights into the evolution of secondary plastids.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {137}, pmid = {30482201}, issn = {1741-7007}, abstract = {BACKGROUND: The evolution of photosynthesis has been a major driver in eukaryotic diversification. Eukaryotes have acquired plastids (chloroplasts) either directly via the engulfment and integration of a photosynthetic cyanobacterium (primary endosymbiosis) or indirectly by engulfing a photosynthetic eukaryote (secondary or tertiary endosymbiosis). The timing and frequency of secondary endosymbiosis during eukaryotic evolution is currently unclear but may be resolved in part by studying cryptomonads, a group of single-celled eukaryotes comprised of both photosynthetic and non-photosynthetic species. While cryptomonads such as Guillardia theta harbor a red algal-derived plastid of secondary endosymbiotic origin, members of the sister group Goniomonadea lack plastids. Here, we present the genome of Goniomonas avonlea-the first for any goniomonad-to address whether Goniomonadea are ancestrally non-photosynthetic or whether they lost a plastid secondarily.

RESULTS: We sequenced the nuclear and mitochondrial genomes of Goniomonas avonlea and carried out a comparative analysis of Go. avonlea, Gu. theta, and other cryptomonads. The Go. avonlea genome assembly is ~ 92 Mbp in size, with 33,470 predicted protein-coding genes. Interestingly, some metabolic pathways (e.g., fatty acid biosynthesis) predicted to occur in the plastid and periplastidal compartment of Gu. theta appear to operate in the cytoplasm of Go. avonlea, suggesting that metabolic redundancies were generated during the course of secondary plastid integration. Other cytosolic pathways found in Go. avonlea are not found in Gu. theta, suggesting secondary loss in Gu. theta and other plastid-bearing cryptomonads. Phylogenetic analyses revealed no evidence for algal endosymbiont-derived genes in the Go. avonlea genome. Phylogenomic analyses point to a specific relationship between Cryptista (to which cryptomonads belong) and Archaeplastida.

CONCLUSION: We found no convincing genomic or phylogenomic evidence that Go. avonlea evolved from a secondary red algal plastid-bearing ancestor, consistent with goniomonads being ancestrally non-photosynthetic eukaryotes. The Go. avonlea genome sheds light on the physiology of heterotrophic cryptomonads and serves as an important reference point for studying the metabolic "rewiring" that took place during secondary plastid integration in the ancestor of modern-day Cryptophyceae.}, } @article {pmid30482188, year = {2018}, author = {Erisman, BE and Barreiros, JP and Rhodes, KL and Warner, RR}, title = {Fake spawns and floating particles: a rebuttal of Karkarey et al. "Alternative reproductive tactics and inverse size-assortment in a high-density fish spawning aggregation".}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {48}, pmid = {30482188}, issn = {1472-6785}, abstract = {Courtship and spawning behaviors of coral reef fishes are very complex, and sufficient sampling effort and proper methods are required to draw informed conclusions on their mating systems that are grounded in contemporary theories of mate choice and sexual selection. We reviewed the recent study by Karkarey et al. (BMC Ecol 17:10, 2017) on the spawning behavior of Squaretail coralgrouper (Plectropomus areolatus) from India and found no evidence to support their findings of alternative reproductive tactics, unique school-spawning involving a single male with multiple females, or inverse size-assortment. The study lacks scientific credibility due to a lack of rigor in the methodology used, misinterpretation of observed behaviors, misinterpretation of the literature, and insufficient data. Their approach led the authors to produce spurious results and profound, invalid conclusions that violate the most basic assumptions of mate choice and sexual selection theory as applied to mating systems in marine fishes.}, } @article {pmid30482182, year = {2018}, author = {McFadden, GI}, title = {Genome of tiny predator with big appetite.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {140}, pmid = {30482182}, issn = {1741-7007}, mesh = {*Appetite ; *Cryptophyta ; Eukaryota/genetics ; Genome ; Photosynthesis ; Plastids ; }, abstract = {The capture and enslavement of eukaryotic algae by unicellular predators to acquire photosynthesis was a major driving force in early eukaryotic diversification. A genome presented in BMC Biology provides a glimpse of how such a tiny predator might have preyed on red algae and detained them to create new lineages of photosynthetic organisms.}, } @article {pmid30482178, year = {2018}, author = {Gallo, G and Presta, L and Perrin, E and Gallo, M and Marchetto, D and Puglia, AM and Fani, R and Baldi, F}, title = {Genomic traits of Klebsiella oxytoca DSM 29614, an uncommon metal-nanoparticle producer strain isolated from acid mine drainages.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {198}, pmid = {30482178}, issn = {1471-2180}, support = {FFR 2012-2013//Università degli Studi di Palermo/ ; FFR 2018//Università degli Studi di Palermo/ ; PRIN-2010AXENJ8//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; FFABR 2017//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; Assegno premiale//Università degli Studi di Firenze/ ; ADiR//Università Ca' Foscari di Venezia/ ; }, abstract = {BACKGROUND: Klebsiella oxytoca DSM 29614 - isolated from acid mine drainages - grows anaerobically using Fe(III)-citrate as sole carbon and energy source, unlike other enterobacteria and K. oxytoca clinical isolates. The DSM 29614 strain is multi metal resistant and produces metal nanoparticles that are embedded in its very peculiar capsular exopolysaccharide. These metal nanoparticles were effective as antimicrobial and anticancer compounds, chemical catalysts and nano-fertilizers.

RESULTS: The DSM 29614 strain genome was sequenced and analysed by a combination of in silico procedures. Comparative genomics, performed between 85 K. oxytoca representatives and K. oxytoca DSM 29614, revealed that this bacterial group has an open pangenome, characterized by a very small core genome (1009 genes, about 2%), a high fraction of unique (43,808 genes, about 87%) and accessory genes (5559 genes, about 11%). Proteins belonging to COG categories "Carbohydrate transport and metabolism" (G), "Amino acid transport and metabolism" (E), "Coenzyme transport and metabolism" (H), "Inorganic ion transport and metabolism" (P), and "membrane biogenesis-related proteins" (M) are particularly abundant in the predicted proteome of DSM 29614 strain. The results of a protein functional enrichment analysis - based on a previous proteomic analysis - revealed metabolic optimization during Fe(III)-citrate anaerobic utilization. In this growth condition, the observed high levels of Fe(II) may be due to different flavin metal reductases and siderophores as inferred form genome analysis. The presence of genes responsible for the synthesis of exopolysaccharide and for the tolerance to heavy metals was highlighted too. The inferred genomic insights were confirmed by a set of phenotypic tests showing specific metabolic capability in terms of i) Fe2+ and exopolysaccharide production and ii) phosphatase activity involved in precipitation of metal ion-phosphate salts.

CONCLUSION: The K. oxytoca DSM 29614 unique capabilities of using Fe(III)-citrate as sole carbon and energy source in anaerobiosis and tolerating diverse metals coincides with the presence at the genomic level of specific genes that can support i) energy metabolism optimization, ii) cell protection by the biosynthesis of a peculiar exopolysaccharide armour entrapping metal ions and iii) general and metal-specific detoxifying activities by different proteins and metabolites.}, } @article {pmid30482177, year = {2018}, author = {Lu, R and Zhang, J and Liu, D and Wei, YL and Wang, Y and Li, XB}, title = {Characterization of bHLH/HLH genes that are involved in brassinosteroid (BR) signaling in fiber development of cotton (Gossypium hirsutum).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {304}, pmid = {30482177}, issn = {1471-2229}, support = {31671255//National Natural Sciences Foundation of China/ ; 2016YFD0100505//National Key R&D Program of China/ ; }, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; Brassinosteroids/*metabolism ; Chromosome Duplication ; Chromosomes, Plant ; Gene Expression Regulation, Plant ; *Genes, Plant ; Gossypium/*genetics/growth & development ; Helix-Loop-Helix Motifs/genetics ; Phylogeny ; Plant Proteins/*genetics ; Signal Transduction/*genetics ; }, abstract = {BACKGROUND: Basic helix-loop-helix/helix-loop-helix (bHLH/HLH) transcription factors play important roles in plant development. Many reports have suggested that bHLH/HLH proteins participate in brassinosteroid (BR) hormone signaling pathways to promote cell elongation. Cotton fibers are single-cells and derived from seed surface. To explore the roles of bHLH/HLH proteins in cotton fiber development progress by modulating BR signaling pathway, we performed a systematic analysis of the bHLH/HLH gene family in upland cotton (Gossypium hirsutum) genome.

RESULTS: In this study, we identified 437 bHLH/HLH genes in upland cotton (G. hirsutum) genome. Phylogenetic analysis revealed that GhbHLH/HLH proteins were split into twenty six clades in the tree. These GhbHLH/HLH genes are distributed unevenly in different chromosomes of cotton genome. Segmental duplication is the predominant gene duplication event and the major contributor for amplification of GhbHLH/HLH gene family. The GhbHLH/HLHs within the same group have conserved exon/intron pattern and their encoding proteins show conserved motif composition. Based on transcriptome data, we identified 77 GhbHLH/HLH candidates that are expressed at relatively high levels in cotton fibers. As adding exogenous BR (brassinolide, BL) or brassinazole (Brz, a BR biosynthesis inhibitor), expressions of these GhbHLH/HLH genes were up-regulated or down-regulated in cotton fibers. Furthermore, overexpression of GhbHLH282 (one of the BR-response genes) in Arabidopsis not only promoted the plant growth, but also changed plant response to BR signaling.

CONCLUSION: Collectively, these data suggested that these GhbHLH/HLH genes may participate in BR signaling transduction during cotton fiber development. Thus, our results may provide a valuable reference data as the basis for further studying the roles of these bHLH/HLH genes in cotton fiber development.}, } @article {pmid30482173, year = {2018}, author = {Bonnici, V and Busato, F and Aldegheri, S and Akhmedov, M and Cascione, L and Carmena, AA and Bertoni, F and Bombieri, N and Kwee, I and Giugno, R}, title = {Correction to: cuRnet: an R package for graph traversing on GPU.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {456}, pmid = {30482173}, issn = {1471-2105}, abstract = {After publication of this supplement article [1], it was brought to our attention that reference 10 and reference 12 in the article are incorrect.}, } @article {pmid30482172, year = {2018}, author = {Liu, Q and Chen, P and Wang, B and Zhang, J and Li, J}, title = {dbMPIKT: a database of kinetic and thermodynamic mutant protein interactions.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {455}, pmid = {30482172}, issn = {1471-2105}, support = {61672035 and 61472282//National Natural Science Foundation of China/ ; }, mesh = {*Databases, Protein ; Internet ; Kinetics ; Mutant Proteins/*metabolism ; Mutation/genetics ; Protein Binding ; Protein Interaction Maps ; Thermodynamics ; }, abstract = {BACKGROUND: Protein-protein interactions (PPIs) play important roles in biological functions. Studies of the effects of mutants on protein interactions can provide further understanding of PPIs. Currently, many databases collect experimental mutants to assess protein interactions, but most of these databases are old and have not been updated for several years.

RESULTS: To address this issue, we manually curated a kinetic and thermodynamic database of mutant protein interactions (dbMPIKT) that is freely accessible at our website. This database contains 5291 mutants in protein interactions collected from previous databases and the literature published within the last three years. Furthermore, some data analysis, such as mutation number, mutation type, protein pair source and network map construction, can be performed online.

CONCLUSION: Our work can promote the study on PPIs, and novel information can be mined from the new database. Our database is available in http://DeepLearner.ahu.edu.cn/web/dbMPIKT/ for use by all, including both academics and non-academics.}, } @article {pmid30482162, year = {2018}, author = {Zalutskaya, Z and Kochemasova, L and Ermilova, E}, title = {Dual positive and negative control of Chlamydomonas PII signal transduction protein expression by nitrate/nitrite and NO via the components of nitric oxide cycle.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {305}, pmid = {30482162}, issn = {1471-2229}, support = {1.65.38.2017//Saint Petersburg State University/ ; }, mesh = {Chlamydomonas/genetics/*metabolism ; Gene Expression Regulation ; Metabolic Networks and Pathways ; Nitrates/*metabolism ; Nitric Oxide/*metabolism ; Nitrites/*metabolism ; PII Nitrogen Regulatory Proteins/*metabolism ; Transcription, Genetic ; }, abstract = {BACKGROUND: The PII proteins constitute a large superfamily, present in all domains of life. Until now, PII proteins research in Chloroplastida (green algae and land plants) has mainly focused on post-translation regulation of these signal transductors. Emerging evidence suggests that PII level is tightly controlled with regard to the nitrogen source and the physiological state of cells.

RESULT: Here we identify that a balance of positive (nitrate and nitrite) and negative (nitric oxide) signals regulates Chlamydomonas GLB1. We found that PII expression is downregulated by ammonium through a nitric oxide (NO)-dependent mechanism. We show that nitrate reductase (NR) and its partner, truncated hemoglobin 1 (THB1), participate in a signaling pathway for dual control of GLB1 expression. Moreover, NO dependent guanilate cyclase appeared to be involved in the negative control of GLB1 transcription.

CONCLUSION: This study has revealed the existence of the complex GLB1 control at transcription level, which is dependent on nitrogen source. Importantly, we found that GLB1 gene expression pattern is very similar to that observed for nitrate assimilation genes, suggesting interconnecting/coordinating PII-dependent and nitrate assimilation pathways.}, } @article {pmid30482158, year = {2018}, author = {Li, JX and Zhu, XH and Li, Y and Liu, Y and Qian, ZH and Zhang, XX and Sun, Y and Ji, LY}, title = {Adaptive genetic differentiation in Pterocarya stenoptera (Juglandaceae) driven by multiple environmental variables were revealed by landscape genomics.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {306}, pmid = {30482158}, issn = {1471-2229}, mesh = {Adaptation, Physiological/*genetics ; China ; *Gene-Environment Interaction ; Genetic Markers ; *Genetic Variation ; Genetics, Population ; Genome, Plant ; Juglandaceae/*genetics ; }, abstract = {BACKGROUND: The investigation of the genetic basis of local adaptation in non-model species is an interesting focus of evolutionary biologists and molecular ecologists. Identifying these adaptive genetic variabilities on the genome responsible can provide insight into the genetic mechanism of local adaptation.

RESULTS: We investigated the spatial distribution of genetic variation in 22 natural populations of Pterocarya stenoptera across its distribution area in China to provide insights into the complex interplay between multiple environmental variables and adaptive genetic differentiation. The Bayesian analysis of population structure showed that the 22 populations of P. stenoptera were subdivided into two groups. Redundancy analysis demonstrated that this genetic differentiation was caused by the divergent selection of environmental difference. A total of 44 outlier loci were mutually identified by Arlequin and BayeScan, 43 of which were environment-associated loci (EAL). The results of latent factor mixed model analysis showed that solar radiation in June (Sr6), minimum temperature of the coldest month (Bio6), temperature seasonality (Bio4), and water vapor pressure in January (Wvp1) were associated with the highest numbers of EAL. Sr6 was associated with the ecological habitat of "prefered light", and Bio6 and Wvp1 were associated with the ecological habitat of "warm and humid environment".

CONCLUSIONS: Our results provided empirical evidence that environmental variables related to the ecological habitats of species play key roles in driving adaptive differentiation of species genome.}, } @article {pmid30482156, year = {2018}, author = {Khan, S and Mao, Y and Gao, D and Riaz, S and Niaz, Z and Tang, L and Khan, S and Wang, D}, title = {Identification of proteins responding to pathogen-infection in the red alga Pyropia yezoensis using iTRAQ quantitative proteomics.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {842}, pmid = {30482156}, issn = {1471-2164}, support = {31372517, 31401116, 31672641//National Natural Science Foundation of China/ ; 2015ASKJ02//Scientific and Technological Innovation Project Financially Supported by Qingdao National Laboratory for Marine Science and Technology/ ; 2016DKA30470//Project of National Infrastructure of Fishery Germplasm Resources/ ; 201762016, 201562018, 201564009//Fundamental Research Funds for the Central Universities/ ; na//Program for Chinese Outstanding Talents in Agriculture Scientific Research/ ; }, abstract = {BACKGROUND: Pyropia yezoensis is an important marine crop which, due to its high protein content, is widely used as a seafood in China. Unfortunately, red rot disease, caused by Pythium porphyrae, seriously damages P. yezoensis farms every year in China, Japan, and Korea. Proteomic methods are often used to study the interactions between hosts and pathogens. Therefore, an iTRAQ-based proteomic analysis was used to identify pathogen-responsive proteins following the artificial infection of P. yezoensis with P. porphyrae spores.

RESULTS: A total of 762 differentially expressed proteins were identified, of which 378 were up-regulated and 384 were down-regulated following infection. A large amount of these proteins were involved in disease stress, carbohydrate metabolism, cell signaling, chaperone activity, photosynthesis, and energy metabolism, as annotated in the KEGG database. Overall, the data showed that P. yezoensis resists infection by inhibiting photosynthesis, and energy and carbohydrate metabolism pathways, as supported by changes in the expression levels of related proteins. The expression data are available via ProteomeXchange with the identifier PXD009363.

CONCLUSIONS: The current data provide an overall summary of the red algae responses to pathogen infection. This study improves our understanding of infection resistance in P. yezoensis, and may help in increasing the breeding of P. porphyrae-infection tolerant macroalgae.}, } @article {pmid30482155, year = {2018}, author = {Lin, S and Wang, C and Zarei, S and Bell, DA and Kerr, SE and Runger, GC and Kocher, JA}, title = {A data science approach for the classification of low-grade and high-grade ovarian serous carcinomas.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {841}, pmid = {30482155}, issn = {1471-2164}, support = {P50 CA136393//Mayo Clinic Ovarian SPORE/ ; }, abstract = {BACKGROUND: Copy Number Alternations (CNAs) is defined as somatic gain or loss of DNA regions. The profiles of CNAs may provide a fingerprint specific to a tumor type or tumor grade. Low-coverage sequencing for reporting CNAs has recently gained interest since successfully translated into clinical applications. Ovarian serous carcinomas can be classified into two largely mutually exclusive grades, low grade and high grade, based on their histologic features. The grade classification based on the genomics may provide valuable clue on how to best manage these patients in clinic. Based on the study of ovarian serous carcinomas, we explore the methodology of combining CNAs reporting from low-coverage sequencing with machine learning techniques to stratify tumor biospecimens of different grades.

RESULTS: We have developed a data-driven methodology for tumor classification using the profiles of CNAs reported by low-coverage sequencing. The proposed method called Bag-of-Segments is used to summarize fixed-length CNA features predictive of tumor grades. These features are further processed by machine learning techniques to obtain classification models. High accuracy is obtained for classifying ovarian serous carcinoma into high and low grades based on leave-one-out cross-validation experiments. The models that are weakly influenced by the sequence coverage and the purity of the sample can also be built, which would be of higher relevance for clinical applications. The patterns captured by Bag-of-Segments features correlate with current clinical knowledge: low grade ovarian tumors being related to aneuploidy events associated to mitotic errors while high grade ovarian tumors are induced by DNA repair gene malfunction.

CONCLUSIONS: The proposed data-driven method obtains high accuracy with various parametrizations for the ovarian serous carcinoma study, indicating that it has good generalization potential towards other CNA classification problems. This method could be applied to the more difficult task of classifying ovarian serous carcinomas with ambiguous histology or in those with low grade tumor co-existing with high grade tumor. The closer genomic relationship of these tumor samples to low or high grade may provide important clinical value.}, } @article {pmid30481613, year = {2018}, author = {Kalel, VC and Mäser, P and Sattler, M and Erdmann, R and Popowicz, GM}, title = {Come, sweet death: targeting glycosomal protein import for antitrypanosomal drug development.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {116-122}, doi = {10.1016/j.mib.2018.11.003}, pmid = {30481613}, issn = {1879-0364}, abstract = {Glycosomes evolved as specialized system for glycolysis in trypanosomatids. These organelle rely on protein import to maintain function. A machinery of peroxin (PEX) proteins is responsible for recognition and transport of glycosomal proteins to the organelle. Disruption of PEX-based import system was expected to be a strategy against trypanosomatids. Recently, a proof of this hypothesis has been presented. Here, we review current information about trypanosomatids' glycosomal transport components as targets for new trypanocidal therapies.}, } @article {pmid30481406, year = {2018}, author = {Escalona Sulbarán, MD and Ivo Simões, P and Gonzalez-Voyer, A and Castroviejo-Fisher, S}, title = {Neotropical frogs and mating songs: the evolution of advertisement calls in glassfrogs.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13406}, pmid = {30481406}, issn = {1420-9101}, support = {1578956//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)/ ; 140815/2018-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; }, abstract = {Anurans emit advertisement calls with the purpose of attracting mates and repelling conspecific competitors. The evolution of call traits is expected to be associated with the evolution of anatomical and behavioural traits due to the physics of call emission and transmission. The evolution of vocalizations might imply trade-offs with other energetically costly behaviours, such as parental care. Here, we investigated the association between body size, calling site, parental care and call properties (call duration, number of notes, peak frequency, frequency bandwidth and call structure) of the advertisement calls of glassfrogs (Centrolenidae)-a family of Neotropical, leaf-dwelling anurans-using phylogenetic comparative methods. We also explored the tempo and mode of evolution of these traits and compared them with those of three morphological traits associated with body size, locomotion and feeding. We generated and compiled acoustic data for 72 glassfrog species (46% of total species richness), including representatives of all genera. We found that almost all acoustic traits have significant, but generally modest, phylogenetic signal. Peak frequency of calls is significantly associated with body size, whereas call structure is significantly associated with calling site and paternal care. Thus, the evolution of body size, calling site and paternal care could constrain call evolution. The estimated disparity of acoustic traits was larger than that of morphological traits and the peak in disparity of acoustic traits generally occurred later in the evolution of glassfrogs, indicating a historically recent outset of the acoustic divergence in this clade.}, } @article {pmid30481396, year = {2018}, author = {Holdaway, S}, title = {Harold Lewis Dibble (July 26, 1951-June 10, 2018).}, journal = {Evolutionary anthropology}, volume = {27}, number = {6}, pages = {254-255}, doi = {10.1002/evan.21749}, pmid = {30481396}, issn = {1520-6505}, } @article {pmid30481341, year = {2018}, author = {Kuang, WM and Ming, C and Li, HP and Wu, H and Frantz, L and Roos, C and Zhang, YP and Zhang, CL and Jia, T and Yang, JY and Yu, L}, title = {The origin and population history of the endangered golden snub-nosed monkey (Rhinopithecus roxellana).}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy220}, pmid = {30481341}, issn = {1537-1719}, abstract = {The origin and population history of the endangered golden snub-nosed monkey (Rhinopitheucs roxellana) remain largely unavailable and/or controversial. We here integrate analyses of multiple genomic markers including mitochondrial (mt) genomes, Y chromosomes and autosomes of 54 golden monkey individuals from all three geographic populations (SG, QL and SNJ). Our results reveal contrasting population structures. Mt analyses suggest a division of golden monkeys into five lineages, one in SNJ and two in SG and two in QL. One of the SG lineages (a mixed SG/QL lineage) is basal to all other lineages. In contrast, autosomal analyses place SNJ as the most basal lineage and identify one QL and three SG lineages. Notably, Y analyses bears features similar to mt analyses in placing the SG/QL-mixed lineage as the first-diverging lineage and dividing SG into two lineages, while resembles autosomal analyses in identifying one QL lineage. We further find bi-directional gene flow among all three populations at autosomal loci, while asymmetric gene flow is suggested at mt genomes and Y chromosomes. We propose that different population structures and gene flow scenarios are the result of sex-linked differences in the dispersal pattern of R. roxellana. Moreover, our demographic simulation analyses support an origin hypothesis suggesting that the ancestral R. roxellana population was once widespread and then divided into SNJ and non-SNJ (SG and QL) populations. This differs from previous mt-based "mono-origin (SG is the source population)" and "multi-origin (SG is a fusion of QL and SNJ)" hypotheses. We provide a detailed and refined scenario for the origin and population history of this endangered primate species, which has a broader significance of Chinese biogeography. In addition, this study highlights the importance to investigate multiple genomic markers with different modes of inheritance to trace the complete evolutionary history of a species especially for those exhibiting differential or mixed patterns of sex dispersal.}, } @article {pmid30480867, year = {2018}, author = {Oke, KB and Motivans, E and Quinn, TP and Hendry, AP}, title = {Sexual dimorphism modifies habitat-associated divergence: evidence from beach and creek breeding sockeye salmon.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13407}, pmid = {30480867}, issn = {1420-9101}, support = {//Pacific salmon seafood industry/ ; //Gordon and Betty Moore Foundation/ ; //U.S. National Science Foundation/ ; //H. Mason Keeler Endowment and the Richard and Lois Worthington Endowment at the University of Washington/ ; }, abstract = {Studies of parallel or convergent evolution (the repeated, independent evolution of similar traits in similar habitats) rarely explicitly quantify the extent of parallelism (i.e. variation in the direction and/or magnitude of divergence) between the sexes; instead, they often investigate both sexes together or exclude one sex. However, differences in male and female patterns of divergence could contribute to overall variation in the extent of parallelism among ecotype pairs, especially in sexually dimorphic traits. Failing to properly attribute such variation could lead to underestimates of the importance of environmental variation in shaping phenotypes. We investigate the extent of parallelism in the body shape of male and female beach and creek spawning sockeye salmon (Oncorhynchus nerka) from two lake systems in western Alaska that were colonized independently after the last ice age. Although both sexes showed some degree of parallelism, patterns of beach-creek body shape divergence vary between the sexes and between lake systems. Phenotypic change vector analyses revealed highly parallel aspects of divergence between males from different lake systems (males from beaches had deeper bodies than males from creeks) but weaker parallelism in females and high parallelism between the sexes in one lake system but not the other. Body shape also had population-specific components, which were mostly, but not entirely, explained by environmental variation in the form of creek depth. Our results highlight the importance of explicitly considering the extent of parallelism between the sexes and environmental variation among sites within habitat types.}, } @article {pmid30480511, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 11 of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003152}, pmid = {30480511}, issn = {1466-5034}, } @article {pmid30480510, year = {2019}, author = {Fang, C and Wu, YH and Sun, C and Wang, H and Cheng, H and Meng, FX and Wang, CS and Xu, XW}, title = {Erythrobacter zhengii sp. nov., a bacterium isolated from deep-sea sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {241-248}, doi = {10.1099/ijsem.0.003136}, pmid = {30480510}, issn = {1466-5034}, abstract = {A Gram-stain-negative, strictly aerobic, rod-shaped bacterium, designated V18T, was isolated from a deep-sea sediment sample collected from the Pacific Ocean and subjected to a polyphasic taxonomic investigation. Cells of strain V18T grew in medium containing 0-10.0 % (w/v) NaCl (optimum 1.0 %), at pH 5.5-9.0 (optimum 6.5-7.0) and at 10-40 °C (optimum 30-37 °C). Aesculin and Tweens 20, 40, 60 and 80 were hydrolysed. The isolate contained carotenoid-like pigments and lacked bacteriochlorophyll a. Strain V18T was closely related to members of the genus Erythrobacter, namely Erythrobacter odishensis JA747T (98.9 % 16S rRNA gene sequence similarity), E. westpacificensis JLT2008T (98.8 %), E. gangjinensis K7-2T (97.7 %), E. aquimixticola JSSK-14T (97.6 %), E. marinus KCTC 23554T (97.4 %), E. atlanticus s21-N3T (97.3 %), E. arachoides RC4-10-4T (97.2 %), E. citreus RE35F/1T (97.1 %) and E. luteus KA37T (97.0 %), and exhibited less than 97.0 % sequence similarity with the type strains of other species with validly published names. Phylogenetic analyses revealed that strain V18T clustered with E. odishensis JA747T and formed an independent lineage. The average nucleotide identity and in silico DNA-DNA hybridization values between strain V18T and the type strains of Erythrobacter species were 70.5-83.4 % and 18.4-26.1 %, respectively. Strain V18T contained ubiquinone 10 (Q-10) as the sole respiratory quinone. The major fatty acids (>10 %) were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The major polar lipids were sphingoglycolipid (SGL), diphosphatidylglycerol (DPG), phosphatidyglycerol (PG), phosphatidylethanolamine (PE) and one unidentified lipid (L1). The DNA G+C content was 62.6 mol%. According to the phenotypic, chemotaxonomic and phylogenetic data, strain V18T represents a novel species of the genus Erythrobacter, for which the name Erythrobacter zhengii is proposed. The type strain is V18T (=KCTC 62389T=MCCC 1K03475T).}, } @article {pmid30479392, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {633}, doi = {10.1038/d41586-018-07537-0}, pmid = {30479392}, issn = {1476-4687}, } @article {pmid30479391, year = {2018}, author = {Antes, A}, title = {First law of leadership: be human first, scientist second.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {601}, doi = {10.1038/d41586-018-07530-7}, pmid = {30479391}, issn = {1476-4687}, } @article {pmid30479390, year = {2018}, author = {Payne, D}, title = {Juggling research and family life: honest reflections from scientist dads.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {725-727}, doi = {10.1038/d41586-018-07511-w}, pmid = {30479390}, issn = {1476-4687}, } @article {pmid30479388, year = {2018}, author = {Tollefson, J}, title = {First sun-dimming experiment will test a way to cool Earth.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {613-615}, doi = {10.1038/d41586-018-07533-4}, pmid = {30479388}, issn = {1476-4687}, } @article {pmid30479383, year = {2019}, author = {Dong, Y and Zhang, S and Wu, Z and Li, X and Wang, WL and Zhu, Y and Stoilova-McPhie, S and Lu, Y and Finley, D and Mao, Y}, title = {Cryo-EM structures and dynamics of substrate-engaged human 26S proteasome.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {49-55}, doi = {10.1038/s41586-018-0736-4}, pmid = {30479383}, issn = {1476-4687}, support = {R01 GM043601/GM/NIGMS NIH HHS/United States ; UM1 AI100645/AI/NIAID NIH HHS/United States ; 1541959//National Science Foundation/International ; }, abstract = {The proteasome is an ATP-dependent, 2.5-megadalton molecular machine that is responsible for selective protein degradation in eukaryotic cells. Here we present cryo-electron microscopy structures of the substrate-engaged human proteasome in seven conformational states at 2.8-3.6 Å resolution, captured during breakdown of a polyubiquitylated protein. These structures illuminate a spatiotemporal continuum of dynamic substrate-proteasome interactions from ubiquitin recognition to substrate translocation, during which ATP hydrolysis sequentially navigates through all six ATPases. There are three principal modes of coordinated hydrolysis, featuring hydrolytic events in two oppositely positioned ATPases, in two adjacent ATPases and in one ATPase at a time. These hydrolytic modes regulate deubiquitylation, initiation of translocation and processive unfolding of substrates, respectively. Hydrolysis of ATP powers a hinge-like motion in each ATPase that regulates its substrate interaction. Synchronization of ATP binding, ADP release and ATP hydrolysis in three adjacent ATPases drives rigid-body rotations of substrate-bound ATPases that are propagated unidirectionally in the ATPase ring and unfold the substrate.}, } @article {pmid30479382, year = {2018}, author = {Zhang, L and Yu, X and Zheng, L and Zhang, Y and Li, Y and Fang, Q and Gao, R and Kang, B and Zhang, Q and Huang, JY and Konno, H and Guo, X and Ye, Y and Gao, S and Wang, S and Hu, X and Ren, X and Shen, Z and Ouyang, W and Zhang, Z}, title = {Lineage tracking reveals dynamic relationships of T cells in colorectal cancer.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {268-272}, doi = {10.1038/s41586-018-0694-x}, pmid = {30479382}, issn = {1476-4687}, abstract = {T cells are key elements of cancer immunotherapy1 but certain fundamental properties, such as the development and migration of T cells within tumours, remain unknown. The enormous T cell receptor (TCR) repertoire, which is required for the recognition of foreign and self-antigens2, could serve as lineage tags to track these T cells in tumours3. Here we obtained transcriptomes of 11,138 single T cells from 12 patients with colorectal cancer, and developed single T cell analysis by RNA sequencing and TCR tracking (STARTRAC) indices to quantitatively analyse the dynamic relationships among 20 identified T cell subsets with distinct functions and clonalities. Although both CD8+ effector and 'exhausted' T cells exhibited high clonal expansion, they were independently connected with tumour-resident CD8+ effector memory cells, implicating a TCR-based fate decision. Of the CD4+ T cells, most tumour-infiltrating T regulatory (Treg) cells showed clonal exclusivity, whereas certain Treg cell clones were developmentally linked to several T helper (TH) cell clones. Notably, we identified two IFNG+ TH1-like cell clusters in tumours that were associated with distinct IFNγ-regulating transcription factors -the GZMK+ effector memory T cells, which were associated with EOMES and RUNX3, and CXCL13+BHLHE40+ TH1-like cell clusters, which were associated with BHLHE40. Only CXCL13+BHLHE40+ TH1-like cells were preferentially enriched in patients with microsatellite-instable tumours, and this might explain their favourable responses to immune-checkpoint blockade. Furthermore, IGFLR1 was highly expressed in both CXCL13+BHLHE40+ TH1-like cells and CD8+ exhausted T cells and possessed co-stimulatory functions. Our integrated STARTRAC analyses provide a powerful approach to dissect the T cell properties in colorectal cancer comprehensively, and could provide insights into the dynamic relationships of T cells in other cancers.}, } @article {pmid30479069, year = {2018}, author = {Byrne, M and Krauss, SL and Millar, MA and Elliott, CP and Coates, DJ and Yates, C and Binks, RM and Nevill, P and Nistelberger, H and Wardell-Johnson, G and Robinson, T and Butcher, R and Barrett, M and Gibson, N}, title = {Persistence and stochasticity are key determinants of genetic diversity in plants associated with banded iron formation inselbergs.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12477}, pmid = {30479069}, issn = {1469-185X}, abstract = {The high species endemism characteristic of many of the world's terrestrial island systems provides a model for studying evolutionary patterns and processes, yet there has been no synthesis of studies to provide a systematic evaluation of terrestrial island systems in this context. The banded iron formations (BIFs) of south-western Australia are ancient terrestrial island formations occurring within a mosaic of alluvial clay soils, sandplains and occasional granite outcropping, across an old, gently undulating, highly weathered, plateau. Notably, these BIFs display exceptionally high beta plant diversity. Here, we address the determinants and consequences of genetic diversity for BIF-associated plant species through a comprehensive review of all studies on species distribution modelling, phylogenetics, phylogeography, population genetics, life-history traits and ecology. The taxa studied are predominantly narrowly endemic to individual or a few BIF ranges, but some have more regional distributions occurring both on and off BIFs. We compared genetic data for these BIF-endemic species to other localised species globally to assess whether the unique history and ancestry of BIF landscapes has driven distinct genetic responses in plants restricted to this habitat. We also assessed the influence of life-history parameters on patterns of genetic diversity. We found that BIF-endemic species display similar patterns of genetic diversity and structure to other species with localised distributions. Despite often highly restricted distributions, large effective population size or clonal reproduction appears to provide these BIF-endemic species with ecological and evolutionary resilience to environmental stochasticity. We conclude that persistence and stochasticity are key determinants of genetic diversity and its spatial structure within BIF-associated plant species, and that these are key evolutionary processes that should be considered in understanding the biogeography of inselbergs worldwide.}, } @article {pmid30478889, year = {2018}, author = {Hamann, E and Weis, AE and Franks, SJ}, title = {Two decades of evolutionary changes in Brassica rapa in response to fluctuations in precipitation and severe drought.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2682-2696}, doi = {10.1111/evo.13631}, pmid = {30478889}, issn = {1558-5646}, support = {# P2BSP3_168833//Swiss National Science Foundation/ ; DEB-1142784//National Science Foundation/ ; IOS-1546218//National Science Foundation/ ; //Natural Sciences and Engineering Research Council of Canada/ ; 1142784//Division of Environmental Biology/ ; 1546218//Division of Integrative Organismal Systems/ ; P2BSP3_168833//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, abstract = {As climate changes at unprecedented rates, understanding population responses is a major challenge. Resurrection studies can provide crucial insights into the contemporary evolution of species to climate change. We used a seed collection of two Californian populations of the annual plant Brassica rapa made over two decades of dramatic precipitation fluctuations, including increasingly severe droughts. We compared flowering phenology, other drought response traits, and seed production among four generations, grown under drought and control conditions, to test for evolutionary change and to characterize the strength and direction of selection. Postdrought generations flowered earlier, with a reduced stem diameter, and lower water-use efficiency (WUE), while intervening wet seasons reversed these adaptations. There was selection for earlier flowering, which was adaptive, but delayed flowering after wet years resulted in reduced total seed mass, indicating a maladaptive response caused by brief wet periods. Furthermore, evolutionary changes and plastic responses often differed in magnitude between populations and drought periods, suggesting independent adaptive pathways. While B. rapa rapidly evolved a drought escape strategy, plant fitness was reduced in contemporary generations, suggesting that rapid shifts in flowering time may no longer keep up with the increasing severity of drought periods, especially when drought adaptation is slowed by occasional wet seasons.}, } @article {pmid30478444, year = {2019}, author = {Demontis, D and Walters, RK and Martin, J and Mattheisen, M and Als, TD and Agerbo, E and Baldursson, G and Belliveau, R and Bybjerg-Grauholm, J and Bækvad-Hansen, M and Cerrato, F and Chambert, K and Churchhouse, C and Dumont, A and Eriksson, N and Gandal, M and Goldstein, JI and Grasby, KL and Grove, J and Gudmundsson, OO and Hansen, CS and Hauberg, ME and Hollegaard, MV and Howrigan, DP and Huang, H and Maller, JB and Martin, AR and Martin, NG and Moran, J and Pallesen, J and Palmer, DS and Pedersen, CB and Pedersen, MG and Poterba, T and Poulsen, JB and Ripke, S and Robinson, EB and Satterstrom, FK and Stefansson, H and Stevens, C and Turley, P and Walters, GB and Won, H and Wright, MJ and , and , and , and Andreassen, OA and Asherson, P and Burton, CL and Boomsma, DI and Cormand, B and Dalsgaard, S and Franke, B and Gelernter, J and Geschwind, D and Hakonarson, H and Haavik, J and Kranzler, HR and Kuntsi, J and Langley, K and Lesch, KP and Middeldorp, C and Reif, A and Rohde, LA and Roussos, P and Schachar, R and Sklar, P and Sonuga-Barke, EJS and Sullivan, PF and Thapar, A and Tung, JY and Waldman, ID and Medland, SE and Stefansson, K and Nordentoft, M and Hougaard, DM and Werge, T and Mors, O and Mortensen, PB and Daly, MJ and Faraone, SV and Børglum, AD and Neale, BM}, title = {Discovery of the first genome-wide significant risk loci for attention deficit/hyperactivity disorder.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {63-75}, doi = {10.1038/s41588-018-0269-7}, pmid = {30478444}, issn = {1546-1718}, support = {R01 MH094469/MH/NIMH NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; U01 MH094432/MH/NIMH NIH HHS/United States ; U01 MH109539/MH/NIMH NIH HHS/United States ; }, abstract = {Attention deficit/hyperactivity disorder (ADHD) is a highly heritable childhood behavioral disorder affecting 5% of children and 2.5% of adults. Common genetic variants contribute substantially to ADHD susceptibility, but no variants have been robustly associated with ADHD. We report a genome-wide association meta-analysis of 20,183 individuals diagnosed with ADHD and 35,191 controls that identifies variants surpassing genome-wide significance in 12 independent loci, finding important new information about the underlying biology of ADHD. Associations are enriched in evolutionarily constrained genomic regions and loss-of-function intolerant genes and around brain-expressed regulatory marks. Analyses of three replication studies: a cohort of individuals diagnosed with ADHD, a self-reported ADHD sample and a meta-analysis of quantitative measures of ADHD symptoms in the population, support these findings while highlighting study-specific differences on genetic overlap with educational attainment. Strong concordance with GWAS of quantitative population measures of ADHD symptoms supports that clinical diagnosis of ADHD is an extreme expression of continuous heritable traits.}, } @article {pmid30478443, year = {2019}, author = {Heyn, P and Logan, CV and Fluteau, A and Challis, RC and Auchynnikava, T and Martin, CA and Marsh, JA and Taglini, F and Kilanowski, F and Parry, DA and Cormier-Daire, V and Fong, CT and Gibson, K and Hwa, V and Ibáñez, L and Robertson, SP and Sebastiani, G and Rappsilber, J and Allshire, RC and Reijns, MAM and Dauber, A and Sproul, D and Jackson, AP}, title = {Gain-of-function DNMT3A mutations cause microcephalic dwarfism and hypermethylation of Polycomb-regulated regions.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {96-105}, doi = {10.1038/s41588-018-0274-x}, pmid = {30478443}, issn = {1546-1718}, support = {R01 HD078592/HD/NICHD NIH HHS/United States ; }, abstract = {DNA methylation and Polycomb are key factors in the establishment of vertebrate cellular identity and fate. Here we report de novo missense mutations in DNMT3A, which encodes the DNA methyltransferase DNMT3A. These mutations cause microcephalic dwarfism, a hypocellular disorder of extreme global growth failure. Substitutions in the PWWP domain abrogate binding to the histone modifications H3K36me2 and H3K36me3, and alter DNA methylation in patient cells. Polycomb-associated DNA methylation valleys, hypomethylated domains encompassing developmental genes, become methylated with concomitant depletion of H3K27me3 and H3K4me3 bivalent marks. Such de novo DNA methylation occurs during differentiation of Dnmt3aW326R pluripotent cells in vitro, and is also evident in Dnmt3aW326R/+ dwarf mice. We therefore propose that the interaction of the DNMT3A PWWP domain with H3K36me2 and H3K36me3 normally limits DNA methylation of Polycomb-marked regions. Our findings implicate the interplay between DNA methylation and Polycomb at key developmental regulators as a determinant of organism size in mammals.}, } @article {pmid30478442, year = {2019}, author = {Zou, J and Huss, M and Abid, A and Mohammadi, P and Torkamani, A and Telenti, A}, title = {A primer on deep learning in genomics.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {12-18}, doi = {10.1038/s41588-018-0295-5}, pmid = {30478442}, issn = {1546-1718}, abstract = {Deep learning methods are a class of machine learning techniques capable of identifying highly complex patterns in large datasets. Here, we provide a perspective and primer on deep learning applications for genome analysis. We discuss successful applications in the fields of regulatory genomics, variant calling and pathogenicity scores. We include general guidance for how to effectively use deep learning methods as well as a practical guide to tools and resources. This primer is accompanied by an interactive online tutorial.}, } @article {pmid30478441, year = {2019}, author = {Moore, R and Casale, FP and Jan Bonder, M and Horta, D and , and Franke, L and Barroso, I and Stegle, O}, title = {A linear mixed-model approach to study multivariate gene-environment interactions.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {180-186}, doi = {10.1038/s41588-018-0271-0}, pmid = {30478441}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Different exposures, including diet, physical activity, or external conditions can contribute to genotype-environment interactions (G×E). Although high-dimensional environmental data are increasingly available and multiple exposures have been implicated with G×E at the same loci, multi-environment tests for G×E are not established. Here, we propose the structured linear mixed model (StructLMM), a computationally efficient method to identify and characterize loci that interact with one or more environments. After validating our model using simulations, we applied StructLMM to body mass index in the UK Biobank, where our model yields previously known and novel G×E signals. Finally, in an application to a large blood eQTL dataset, we demonstrate that StructLMM can be used to study interactions with hundreds of environmental variables.}, } @article {pmid30478440, year = {2019}, author = {Urbut, SM and Wang, G and Carbonetto, P and Stephens, M}, title = {Flexible statistical methods for estimating and testing effects in genomic studies with multiple conditions.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {187-195}, doi = {10.1038/s41588-018-0268-8}, pmid = {30478440}, issn = {1546-1718}, support = {R01 HG002585/HG/NHGRI NIH HHS/United States ; R01 MH101825/MH/NIMH NIH HHS/United States ; }, abstract = {We introduce new statistical methods for analyzing genomic data sets that measure many effects in many conditions (for example, gene expression changes under many treatments). These new methods improve on existing methods by allowing for arbitrary correlations in effect sizes among conditions. This flexible approach increases power, improves effect estimates and allows for more quantitative assessments of effect-size heterogeneity compared to simple shared or condition-specific assessments. We illustrate these features through an analysis of locally acting variants associated with gene expression (cis expression quantitative trait loci (eQTLs)) in 44 human tissues. Our analysis identifies more eQTLs than existing approaches, consistent with improved power. We show that although genetic effects on expression are extensively shared among tissues, effect sizes can still vary greatly among tissues. Some shared eQTLs show stronger effects in subsets of biologically related tissues (for example, brain-related tissues), or in only one tissue (for example, testis). Our methods are widely applicable, computationally tractable for many conditions and available online.}, } @article {pmid30478438, year = {2018}, author = {Mondal, M and Casals, F and Majumder, PP and Bertranpetit, J}, title = {Reply to 'No evidence for unknown archaic ancestry in South Asia'.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1637-1639}, doi = {10.1038/s41588-018-0280-z}, pmid = {30478438}, issn = {1546-1718}, } @article {pmid30478436, year = {2019}, author = {Kumasaka, N and Knights, AJ and Gaffney, DJ}, title = {High-resolution genetic mapping of putative causal interactions between regions of open chromatin.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {128-137}, doi = {10.1038/s41588-018-0278-6}, pmid = {30478436}, issn = {1546-1718}, abstract = {Physical interaction of regulatory elements in three-dimensional space poses a challenge for studies of disease because non-coding risk variants may be great distances from the genes they regulate. Experimental methods to capture these interactions, such as chromosome conformation capture, usually cannot assign causal direction of effect between regulatory elements, an important component of fine-mapping studies. We developed a Bayesian hierarchical approach that uses two-stage least squares and applied it to an ATAC-seq (assay for transposase-accessible chromatin using sequencing) data set from 100 individuals, to identify over 15,000 high-confidence causal interactions. Most (60%) interactions occurred over <20 kb, where chromosome conformation capture-based methods perform poorly. For a fraction of loci, we identified a single variant that alters accessibility across multiple regions, and experimentally validated the BLK locus, which is associated with multiple autoimmune diseases, using CRISPR genome editing. Our study highlights how association genetics of chromatin state is a powerful approach for identifying interactions between regulatory elements.}, } @article {pmid30478390, year = {2018}, author = {}, title = {Professional titles matter.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1329}, doi = {10.1038/s41564-018-0320-6}, pmid = {30478390}, issn = {2058-5276}, } @article {pmid30478389, year = {2018}, author = {Tan, JMJ and Mellouk, N and Osborne, SE and Ammendolia, DA and Dyer, DN and Li, R and Brunen, D and van Rijn, JM and Huang, J and Czuczman, MA and Cemma, MA and Won, AM and Yip, CM and Xavier, RJ and MacDuff, DA and Reggiori, F and Debnath, J and Yoshimori, T and Kim, PK and Fairn, GD and Coyaud, E and Raught, B and Muise, AM and Higgins, DE and Brumell, JH}, title = {An ATG16L1-dependent pathway promotes plasma membrane repair and limits Listeria monocytogenes cell-to-cell spread.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1472-1485}, doi = {10.1038/s41564-018-0293-5}, pmid = {30478389}, issn = {2058-5276}, abstract = {Plasma membrane integrity is essential for the viability of eukaryotic cells. In response to bacterial pore-forming toxins, disrupted regions of the membrane are rapidly repaired. However, the pathways that mediate plasma membrane repair are unclear. Here we show that autophagy-related (ATG) protein ATG16L1 and its binding partners ATG5 and ATG12 are required for plasma membrane repair through a pathway independent of macroautophagy. ATG16L1 is required for lysosome fusion with the plasma membrane and blebbing responses that promote membrane repair. ATG16L1 deficiency causes accumulation of cholesterol in lysosomes that contributes to defective membrane repair. Cell-to-cell spread by Listeria monocytogenes requires membrane damage by the bacterial toxin listeriolysin O, which is restricted by ATG16L1-dependent membrane repair. Cells harbouring the ATG16L1 T300A allele associated with inflammatory bowel disease were also found to accumulate cholesterol and be defective in repair, linking a common inflammatory disease to plasma membrane integrity. Thus, plasma membrane repair could be an important therapeutic target for the treatment of bacterial infections and inflammatory disorders.}, } @article {pmid30478388, year = {2018}, author = {Doyle, T and Moncorgé, O and Bonaventure, B and Pollpeter, D and Lussignol, M and Tauziet, M and Apolonia, L and Catanese, MT and Goujon, C and Malim, MH}, title = {The interferon-inducible isoform of NCOA7 inhibits endosome-mediated viral entry.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1369-1376}, doi = {10.1038/s41564-018-0273-9}, pmid = {30478388}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; R01 DA033773/DA/NIDA NIH HHS/United States ; }, abstract = {Interferons (IFNs) mediate cellular defence against viral pathogens by upregulation of IFN-stimulated genes whose products interact with viral components or alter cellular physiology to suppress viral replication1-3. Among the IFN-stimulated genes that can inhibit influenza A virus (IAV)4 are the myxovirus resistance 1 GTPase5 and IFN-induced transmembrane protein 3 (refs 6,7). Here, we use ectopic expression and gene knockout to demonstrate that the IFN-inducible 219-amino acid short isoform of human nuclear receptor coactivator 7 (NCOA7) is an inhibitor of IAV as well as other viruses that enter the cell by endocytosis, including hepatitis C virus. NCOA7 interacts with the vacuolar H+-ATPase (V-ATPase) and its expression promotes cytoplasmic vesicle acidification, lysosomal protease activity and the degradation of endocytosed antigen. Step-wise dissection of the IAV entry pathway demonstrates that NCOA7 inhibits fusion of the viral and endosomal membranes and subsequent nuclear translocation of viral ribonucleoproteins. Therefore, NCOA7 provides a mechanism for immune regulation of endolysosomal physiology that not only suppresses viral entry into the cytosol from this compartment but may also regulate other V-ATPase-associated cellular processes, such as physiological adjustments to nutritional status, or the maturation and function of antigen-presenting cells.}, } @article {pmid30478387, year = {2018}, author = {Van Lint, C}, title = {Stop HUSHing on SIV/HIV.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1336-1338}, doi = {10.1038/s41564-018-0308-2}, pmid = {30478387}, issn = {2058-5276}, } @article {pmid30478386, year = {2018}, author = {Davidson, AR and Maxwell, KL}, title = {Type VI secretion system baseplate.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1330-1331}, doi = {10.1038/s41564-018-0311-7}, pmid = {30478386}, issn = {2058-5276}, } @article {pmid30478385, year = {2018}, author = {Florey, O}, title = {The double life of autophagy proteins.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1334-1335}, doi = {10.1038/s41564-018-0310-8}, pmid = {30478385}, issn = {2058-5276}, } @article {pmid30478384, year = {2018}, author = {Bultman, SJ}, title = {Bacterial butyrate prevents atherosclerosis.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1332-1333}, doi = {10.1038/s41564-018-0299-z}, pmid = {30478384}, issn = {2058-5276}, } @article {pmid30478373, year = {2018}, author = {}, title = {Beware the rise of the radical right.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {599}, doi = {10.1038/d41586-018-07527-2}, pmid = {30478373}, issn = {1476-4687}, } @article {pmid30478372, year = {2018}, author = {}, title = {How some wind turbines hog the breeze.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {599-600}, doi = {10.1038/d41586-018-07528-1}, pmid = {30478372}, issn = {1476-4687}, } @article {pmid30478371, year = {2018}, author = {Datta, MS and Kishony, R}, title = {A spotlight on bacterial mutations for 75 years.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {633-644}, doi = {10.1038/d41586-018-07521-8}, pmid = {30478371}, issn = {1476-4687}, } @article {pmid30478370, year = {2018}, author = {Masood, E}, title = {A 100th birthday wish: uphold academic freedom in dark times.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {621-623}, doi = {10.1038/d41586-018-07518-3}, pmid = {30478370}, issn = {1476-4687}, } @article {pmid30478369, year = {2018}, author = {Chai, G and Gleeson, JG}, title = {A newly discovered mechanism driving neuronal mutations in Alzheimer's disease.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {631-632}, doi = {10.1038/d41586-018-07334-9}, pmid = {30478369}, issn = {1476-4687}, mesh = {*Alzheimer Disease ; Humans ; Mutation ; *Neurons ; Recombination, Genetic ; }, } @article {pmid30478367, year = {2018}, author = {Mirazón Lahr, M}, title = {The not-so-dangerous lives of Neanderthals.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {634-636}, doi = {10.1038/d41586-018-07343-8}, pmid = {30478367}, issn = {1476-4687}, mesh = {Animals ; Anthropology ; *Hominidae ; Humans ; *Neanderthals ; Prevalence ; }, } @article {pmid30478309, year = {2019}, author = {Borstein, SR and Fordyce, JA and O'Meara, BC and Wainwright, PC and McGee, MD}, title = {Reef fish functional traits evolve fastest at trophic extremes.}, journal = {Nature ecology & evolution}, volume = {3}, number = {2}, pages = {191-199}, doi = {10.1038/s41559-018-0725-x}, pmid = {30478309}, issn = {2397-334X}, abstract = {Trophic ecology is thought to exert a profound influence on biodiversity, but the specifics of the process are rarely examined at large spatial and evolutionary scales. We investigate how trophic position and diet breadth influence functional trait evolution in one of the most species-rich and complex vertebrate assemblages, coral reef fishes, within a large-scale phylogenetic framework. We show that, in contrast with established theory, functional traits evolve fastest in trophic specialists with narrow diet breadths at both very low and high trophic positions. Top trophic level specialists exhibit the most functional diversity, while omnivorous taxa with intermediate trophic positions and wide diet breadth have the least functional diversity. Our results reveal the importance of trophic position in shaping evolutionary dynamics while simultaneously highlighting the incredible trophic and functional diversity present in coral reef fish assemblages.}, } @article {pmid30478308, year = {2019}, author = {Kosintsev, P and Mitchell, KJ and Devièse, T and van der Plicht, J and Kuitems, M and Petrova, E and Tikhonov, A and Higham, T and Comeskey, D and Turney, C and Cooper, A and van Kolfschoten, T and Stuart, AJ and Lister, AM}, title = {Evolution and extinction of the giant rhinoceros Elasmotherium sibiricum sheds light on late Quaternary megafaunal extinctions.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {31-38}, doi = {10.1038/s41559-018-0722-0}, pmid = {30478308}, issn = {2397-334X}, abstract = {Understanding extinction events requires an unbiased record of the chronology and ecology of victims and survivors. The rhinoceros Elasmotherium sibiricum, known as the 'Siberian unicorn', was believed to have gone extinct around 200,000 years ago-well before the late Quaternary megafaunal extinction event. However, no absolute dating, genetic analysis or quantitative ecological assessment of this species has been undertaken. Here, we show, by accelerator mass spectrometry radiocarbon dating of 23 individuals, including cross-validation by compound-specific analysis, that E. sibiricum survived in Eastern Europe and Central Asia until at least 39,000 years ago, corroborating a wave of megafaunal turnover before the Last Glacial Maximum in Eurasia, in addition to the better-known late-glacial event. Stable isotope data indicate a dry steppe niche for E. sibiricum and, together with morphology, a highly specialized diet that probably contributed to its extinction. We further demonstrate, with DNA sequencing data, a very deep phylogenetic split between the subfamilies Elasmotheriinae and Rhinocerotinae that includes all the living rhinoceroses, settling a debate based on fossil evidence and confirming that the two lineages had diverged by the Eocene. As the last surviving member of the Elasmotheriinae, the demise of the 'Siberian unicorn' marked the extinction of this subfamily.}, } @article {pmid30478307, year = {2019}, author = {Armenteras, D and Schneider, L and Dávalos, LM}, title = {Fires in protected areas reveal unforeseen costs of Colombian peace.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {20-23}, doi = {10.1038/s41559-018-0727-8}, pmid = {30478307}, issn = {2397-334X}, abstract = {Armed conflict, and its end, can have powerful effects on natural resources, but the influence of war and peace on highly biodiverse tropical forests remains disputed. We found a sixfold increase in fires in protected areas across biodiversity hotspots following guerrilla demobilization in Colombia, and a 52% increase in the probability of per-pixel deforestation within parks for 2018. Peace requires urgent shifts to include real-time forest monitoring, expand programmes to pay for ecosystem services at the frontier, integrate demobilized armed groups as staff of protected areas, and establish a domestic market for frontier deforestation permits.}, } @article {pmid30478305, year = {2019}, author = {Villanea, FA and Schraiber, JG}, title = {Multiple episodes of interbreeding between Neanderthal and modern humans.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {39-44}, doi = {10.1038/s41559-018-0735-8}, pmid = {30478305}, issn = {2397-334X}, support = {R35 GM124745/GM/NIGMS NIH HHS/United States ; }, abstract = {Neanderthals and anatomically modern humans overlapped geographically for a period of over 30,000 years following human migration out of Africa. During this period, Neanderthals and humans interbred, as evidenced by Neanderthal portions of the genome carried by non-African individuals today. A key observation is that the proportion of Neanderthal ancestry is ~12-20% higher in East Asian individuals relative to European individuals. Here, we explore various demographic models that could explain this observation. These include distinguishing between a single admixture event and multiple Neanderthal contributions to either population, and the hypothesis that reduced Neanderthal ancestry in modern Europeans resulted from more recent admixture with a ghost population that lacked a Neanderthal ancestry component (the 'dilution' hypothesis). To summarize the asymmetric pattern of Neanderthal allele frequencies, we compiled the joint fragment frequency spectrum of European and East Asian Neanderthal fragments and compared it with both analytical theory and data simulated under various models of admixture. Using maximum-likelihood and machine learning, we found that a simple model of a single admixture did not fit the empirical data, and instead favour a model of multiple episodes of gene flow into both European and East Asian populations. These findings indicate a longer-term, more complex interaction between humans and Neanderthals than was previously appreciated.}, } @article {pmid30478294, year = {2018}, author = {Kühne, M and Börrnert, F and Fecher, S and Ghorbani-Asl, M and Biskupek, J and Samuelis, D and Krasheninnikov, AV and Kaiser, U and Smet, JH}, title = {Reversible superdense ordering of lithium between two graphene sheets.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {234-239}, doi = {10.1038/s41586-018-0754-2}, pmid = {30478294}, issn = {1476-4687}, abstract = {Many carbon allotropes can act as host materials for reversible lithium uptake1,2, thereby laying the foundations for existing and future electrochemical energy storage. However, insight into how lithium is arranged within these hosts is difficult to obtain from a working system. For example, the use of in situ transmission electron microscopy3-5 to probe light elements (especially lithium)6,7 is severely hampered by their low scattering cross-section for impinging electrons and their susceptibility to knock-on damage8. Here we study the reversible intercalation of lithium into bilayer graphene by in situ low-voltage transmission electron microscopy, using both spherical and chromatic aberration correction9 to enhance contrast and resolution to the required levels. The microscopy is supported by electron energy-loss spectroscopy and density functional theory calculations. On their remote insertion from an electrochemical cell covering one end of the long but narrow bilayer, we observe lithium atoms to assume multi-layered close-packed order between the two carbon sheets. The lithium storage capacity associated with this superdense phase far exceeds that expected from formation of LiC6, which is the densest configuration known under normal conditions for lithium intercalation within bulk graphitic carbon10. Our findings thus point to the possible existence of distinct storage arrangements of ions in two-dimensional layered materials as compared to their bulk parent compounds.}, } @article {pmid30478293, year = {2018}, author = {LeGates, TA and Kvarta, MD and Tooley, JR and Francis, TC and Lobo, MK and Creed, MC and Thompson, SM}, title = {Reward behaviour is regulated by the strength of hippocampus-nucleus accumbens synapses.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {258-262}, pmid = {30478293}, issn = {1476-4687}, support = {R01 MH086828/MH/NIMH NIH HHS/United States ; R01 MH106500/MH/NIMH NIH HHS/United States ; T32 NS007375/NS/NINDS NIH HHS/United States ; }, abstract = {Reward drives motivated behaviours and is essential for survival, and therefore there is strong evolutionary pressure to retain contextual information about rewarding stimuli. This drive may be abnormally strong, such as in addiction, or weak, such as in depression, in which anhedonia (loss of pleasure in response to rewarding stimuli) is a prominent symptom. Hippocampal input to the shell of the nucleus accumbens (NAc) is important for driving NAc activity1,2 and activity-dependent modulation of the strength of this input may contribute to the proper regulation of goal-directed behaviours. However, there have been few robust descriptions of the mechanisms that underlie the induction or expression of long-term potentiation (LTP) at these synapses, and there is, to our knowledge, no evidence about whether such plasticity contributes to reward-related behaviour. Here we show that high-frequency activity induces LTP at hippocampus-NAc synapses in mice via canonical, but dopamine-independent, mechanisms. The induction of LTP at this synapse in vivo drives conditioned place preference, and activity at this synapse is required for conditioned place preference in response to a natural reward. Conversely, chronic stress, which induces anhedonia, decreases the strength of this synapse and impairs LTP, whereas antidepressant treatment is accompanied by a reversal of these stress-induced changes. We conclude that hippocampus-NAc synapses show activity-dependent plasticity and suggest that their strength may be critical for contextual reward behaviour.}, } @article {pmid30478291, year = {2019}, author = {Ruppé, E and Ghozlane, A and Tap, J and Pons, N and Alvarez, AS and Maziers, N and Cuesta, T and Hernando-Amado, S and Clares, I and Martínez, JL and Coque, TM and Baquero, F and Lanza, VF and Máiz, L and Goulenok, T and de Lastours, V and Amor, N and Fantin, B and Wieder, I and Andremont, A and van Schaik, W and Rogers, M and Zhang, X and Willems, RJL and de Brevern, AG and Batto, JM and Blottière, HM and Léonard, P and Léjard, V and Letur, A and Levenez, F and Weiszer, K and Haimet, F and Doré, J and Kennedy, SP and Ehrlich, SD}, title = {Prediction of the intestinal resistome by a three-dimensional structure-based method.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {112-123}, doi = {10.1038/s41564-018-0292-6}, pmid = {30478291}, issn = {2058-5276}, abstract = {The intestinal microbiota is considered to be a major reservoir of antibiotic resistance determinants (ARDs) that could potentially be transferred to bacterial pathogens via mobile genetic elements. Yet, this assumption is poorly supported by empirical evidence due to the distant homologies between known ARDs (mostly from culturable bacteria) and ARDs from the intestinal microbiota. Consequently, an accurate census of intestinal ARDs (that is, the intestinal resistome) has not yet been fully determined. For this purpose, we developed and validated an annotation method (called pairwise comparative modelling) on the basis of a three-dimensional structure (homology comparative modelling), leading to the prediction of 6,095 ARDs in a catalogue of 3.9 million proteins from the human intestinal microbiota. We found that the majority of predicted ARDs (pdARDs) were distantly related to known ARDs (mean amino acid identity 29.8%) and found little evidence supporting their transfer between species. According to the composition of their resistome, we were able to cluster subjects from the MetaHIT cohort (n = 663) into six resistotypes that were connected to the previously described enterotypes. Finally, we found that the relative abundance of pdARDs was positively associated with gene richness, but not when subjects were exposed to antibiotics. Altogether, our results indicate that the majority of intestinal microbiota ARDs can be considered intrinsic to the dominant commensal microbiota and that these genes are rarely shared with bacterial pathogens.}, } @article {pmid30478290, year = {2019}, author = {Huang, KA and Rijal, P and Jiang, H and Wang, B and Schimanski, L and Dong, T and Liu, YM and Chang, P and Iqbal, M and Wang, MC and Chen, Z and Song, R and Huang, CC and Yang, JH and Qi, J and Lin, TY and Li, A and Powell, TJ and Jan, JT and Ma, C and Gao, GF and Shi, Y and Townsend, AR}, title = {Structure-function analysis of neutralizing antibodies to H7N9 influenza from naturally infected humans.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {306-315}, doi = {10.1038/s41564-018-0303-7}, pmid = {30478290}, issn = {2058-5276}, abstract = {Little is known about the specificities and neutralization breadth of the H7-reactive antibody repertoire induced by natural H7N9 infection in humans. We have isolated and characterized 73 H7-reactive monoclonal antibodies from peripheral B cells from four donors infected in 2013 and 2014. Of these, 45 antibodies were H7-specific, and 17 of these neutralized the virus, albeit with few somatic mutations in their variable domain sequences. An additional set of 28 antibodies, isolated from younger donors born after 1968, cross-reacted between H7 and H3 haemagglutinins in binding assays, and had accumulated significantly more somatic mutations, but were predominantly non-neutralizing in vitro. Crystal structures of three neutralizing and protective antibodies in complex with the H7 haemagglutinin revealed that they recognize overlapping residues surrounding the receptor-binding site of haemagglutinin. One of the antibodies, L4A-14, bound into the sialic acid binding site and made contacts with haemagglutinin residues that were conserved in the great majority of 2016-2017 H7N9 isolates. However, only 3 of the 17 neutralizing antibodies retained activity for the Yangtze River Delta lineage viruses isolated in 2016-2017 that have undergone antigenic change, which emphasizes the need for updated H7N9 vaccines.}, } @article {pmid30478289, year = {2019}, author = {Turgeman-Grott, I and Joseph, S and Marton, S and Eizenshtein, K and Naor, A and Soucy, SM and Stachler, AE and Shalev, Y and Zarkor, M and Reshef, L and Altman-Price, N and Marchfelder, A and Gophna, U}, title = {Pervasive acquisition of CRISPR memory driven by inter-species mating of archaea can limit gene transfer and influence speciation.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {177-186}, doi = {10.1038/s41564-018-0302-8}, pmid = {30478289}, issn = {2058-5276}, abstract = {CRISPR-Cas systems provide prokaryotes with sequence-specific immunity against viruses and plasmids based on DNA acquired from these invaders, known as spacers. Surprisingly, many archaea possess spacers that match chromosomal genes of related species, including those encoding core housekeeping genes. By sequencing genomes of environmental archaea isolated from a single site, we demonstrate that inter-species spacers are common. We show experimentally, by mating Haloferax volcanii and Haloferax mediterranei, that spacers are indeed acquired chromosome-wide, although a preference for integrated mobile elements and nearby regions of the chromosome exists. Inter-species mating induces increased spacer acquisition and may result in interactions between the acquisition machinery of the two species. Surprisingly, many of the spacers acquired following inter-species mating target self-replicons along with those originating from the mating partner, indicating that the acquisition machinery cannot distinguish self from non-self under these conditions. Engineering the chromosome of one species to be targeted by the other's CRISPR-Cas reduces gene exchange between them substantially. Thus, spacers acquired during inter-species mating could limit future gene transfer, resulting in a role for CRISPR-Cas systems in microbial speciation.}, } @article {pmid30478288, year = {2019}, author = {Pollier, J and Vancaester, E and Kuzhiumparambil, U and Vickers, CE and Vandepoele, K and Goossens, A and Fabris, M}, title = {A widespread alternative squalene epoxidase participates in eukaryote steroid biosynthesis.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {226-233}, doi = {10.1038/s41564-018-0305-5}, pmid = {30478288}, issn = {2058-5276}, abstract = {Steroids are essential triterpenoid molecules that are present in all eukaryotes and modulate the fluidity and flexibility of cell membranes. Steroids also serve as signalling molecules that are crucial for growth, development and differentiation of multicellular organisms1-3. The steroid biosynthetic pathway is highly conserved and is key in eukaryote evolution4-7. The flavoprotein squalene epoxidase (SQE) catalyses the first oxygenation reaction in this pathway and is rate limiting. However, despite its conservation in animals, plants and fungi, several phylogenetically widely distributed eukaryote genomes lack an SQE-encoding gene7,8. Here, we discovered and characterized an alternative SQE (AltSQE) belonging to the fatty acid hydroxylase superfamily. AltSQE was identified through screening of a gene library of the diatom Phaeodactylum tricornutum in a SQE-deficient yeast. In accordance with its divergent protein structure and need for cofactors, we found that AltSQE is insensitive to the conventional SQE inhibitor terbinafine. AltSQE is present in many eukaryotic lineages but is mutually exclusive with SQE and shows a patchy distribution within monophyletic clades. Our discovery provides an alternative element for the conserved steroid biosynthesis pathway, raises questions about eukaryote metabolic evolution and opens routes to develop selective SQE inhibitors to control hazardous organisms.}, } @article {pmid30478287, year = {2019}, author = {Lulla, V and Dinan, AM and Hosmillo, M and Chaudhry, Y and Sherry, L and Irigoyen, N and Nayak, KM and Stonehouse, NJ and Zilbauer, M and Goodfellow, I and Firth, AE}, title = {An upstream protein-coding region in enteroviruses modulates virus infection in gut epithelial cells.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {280-292}, doi = {10.1038/s41564-018-0297-1}, pmid = {30478287}, issn = {2058-5276}, abstract = {Enteroviruses comprise a large group of mammalian pathogens that includes poliovirus. Pathology in humans ranges from sub-clinical to acute flaccid paralysis, myocarditis and meningitis. Until now, all of the enteroviral proteins were thought to derive from the proteolytic processing of a polyprotein encoded in a single open reading frame. Here we report that many enterovirus genomes also harbour an upstream open reading frame (uORF) that is subject to strong purifying selection. Using echovirus 7 and poliovirus 1, we confirmed the expression of uORF protein in infected cells. Through ribosome profiling (a technique for the global footprinting of translating ribosomes), we also demonstrated translation of the uORF in representative members of the predominant human enterovirus species, namely Enterovirus A, B and C. In differentiated human intestinal organoids, uORF protein-knockout echoviruses are attenuated compared to the wild-type at late stages of infection where membrane-associated uORF protein facilitates virus release. Thus, we have identified a previously unknown enterovirus protein that facilitates virus growth in gut epithelial cells-the site of initial viral invasion into susceptible hosts. These findings overturn the 50-year-old dogma that enteroviruses use a single-polyprotein gene expression strategy and have important implications for the understanding of enterovirus pathogenesis.}, } @article {pmid30478286, year = {2019}, author = {Bancells, C and Llorà-Batlle, O and Poran, A and Nötzel, C and Rovira-Graells, N and Elemento, O and Kafsack, BFC and Cortés, A}, title = {Revisiting the initial steps of sexual development in the malaria parasite Plasmodium falciparum.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {144-154}, pmid = {30478286}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; R01 CA194547/CA/NCI NIH HHS/United States ; }, abstract = {Human to vector transmission of malaria requires that some blood-stage parasites abandon asexual growth and convert into non-replicating sexual forms called gametocytes. The initial steps of gametocytogenesis remain largely uncharacterized. Here, we study this part of the malaria life cycle in Plasmodium falciparum using PfAP2-G, the master regulator of sexual conversion, as a marker of commitment. We demonstrate the existence of PfAP2-G-positive sexually committed parasite stages that precede the previously known committed schizont stage. We also found that sexual conversion can occur by two different routes: the previously described route in which PfAP2-G-expressing parasites complete a replicative cycle as committed forms before converting into gametocytes upon re-invasion, or a direct route with conversion within the same cycle as initial PfAP2-G expression. The latter route is linked to early PfAP2-G expression in ring stages. Reanalysis of published single-cell RNA-sequencing (RNA-seq) data confirmed the presence of both routes. Consistent with these results, using plaque assays we observed that, in contrast to the prevailing model, many schizonts produced mixed plaques containing both asexual parasites and gametocytes. Altogether, our results reveal unexpected features of the initial steps of sexual development and extend the current view of this part of the malaria life cycle.}, } @article {pmid30478063, year = {2018}, author = {Fischhoff, B}, title = {Evaluating science communication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1805863115}, pmid = {30478063}, issn = {1091-6490}, abstract = {Effective science communication requires assembling scientists with knowledge relevant to decision makers, translating that knowledge into useful terms, establishing trusted two-way communication channels, evaluating the process, and refining it as needed. Communicating Science Effectively: A Research Agenda [National Research Council (2017)] surveys the scientific foundations for accomplishing these tasks, the research agenda for improving them, and the essential collaborative relations with decision makers and communication professionals. Recognizing the complexity of the science, the decisions, and the communication processes, the report calls for a systems approach. This perspective offers an approach to creating such systems by adapting scientific methods to the practical constraints of science communication. It considers staffing (are the right people involved?), internal collaboration (are they talking to one another?), and external collaboration (are they talking to other stakeholders?). It focuses on contexts where the goal of science communication is helping people to make autonomous choices rather than promoting specific behaviors (e.g., voter turnout, vaccination rates, energy consumption). The approach is illustrated with research in two domains: decisions about preventing sexual assault and responding to pandemic disease.}, } @article {pmid30478062, year = {2018}, author = {Abarzhi, SI and Bhowmick, AK and Naveh, A and Pandian, A and Swisher, NC and Stellingwerf, RF and Arnett, WD}, title = {Supernova, nuclear synthesis, fluid instabilities, and interfacial mixing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1714502115}, pmid = {30478062}, issn = {1091-6490}, abstract = {Supernovae and their remnants are a central problem in astrophysics due to their role in the stellar evolution and nuclear synthesis. A supernova's explosion is driven by a blast wave causing the development of Rayleigh-Taylor and Richtmyer-Meshkov instabilities and leading to intensive interfacial mixing of materials of a progenitor star. Rayleigh-Taylor and Richtmyer-Meshkov mixing breaks spherical symmetry of a star and provides conditions for synthesis of heavy mass elements in addition to light mass elements synthesized in the star before its explosion. By focusing on hydrodynamic aspects of the problem, we apply group theory analysis to identify the properties of Rayleigh-Taylor and Richtmyer-Meshkov dynamics with variable acceleration, discover subdiffusive character of the blast wave-induced interfacial mixing, and reveal the mechanism of energy accumulation and transport at small scales in supernovae.}, } @article {pmid30478061, year = {2018}, author = {Manski, CF}, title = {Communicating uncertainty in policy analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1722389115}, pmid = {30478061}, issn = {1091-6490}, abstract = {The term "policy analysis" describes scientific evaluations of the impacts of past public policies and predictions of the outcomes of potential future policies. A prevalent practice has been to report policy analysis with incredible certitude. That is, exact predictions of policy outcomes are routine, while expressions of uncertainty are rare. However, predictions and estimates often are fragile, resting on unsupported assumptions and limited data. Therefore, the expressed certitude is not credible. This paper summarizes my work documenting incredible certitude and calling for transparent communication of uncertainty. I present a typology of practices that contribute to incredible certitude, give illustrative examples, and offer suggestions on how to communicate uncertainty.}, } @article {pmid30478060, year = {2018}, author = {Zhou, Y and Yang, L and Duan, J and Cheng, J and Shen, Y and Wang, X and Han, R and Li, H and Li, Z and Wang, L and Terzaghi, W and Zhu, D and Chen, H and Deng, XW and Li, J}, title = {Hinge region of Arabidopsis phyA plays an important role in regulating phyA function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11864-E11873}, doi = {10.1073/pnas.1813162115}, pmid = {30478060}, issn = {1091-6490}, support = {R01 GM047850/GM/NIGMS NIH HHS/United States ; R37 GM047850/GM/NIGMS NIH HHS/United States ; }, abstract = {Phytochrome A (phyA) is the only plant photoreceptor that perceives far-red light and then mediates various responses to this signal. Phosphorylation and dephosphorylation of oat phyA have been extensively studied, and it was shown that phosphorylation of a serine residue in the hinge region of oat phyA could regulate the interaction of phyA with its signal transducers. However, little is known about the role of the hinge region of Arabidopsis phyA. Here, we report that three sites in the hinge region of Arabidopsis phyA (i.e., S590, T593, and S602) are essential in regulating phyA function. Mutating all three of these sites to either alanines or aspartic acids impaired phyA function, changed the interactions of mutant phyA with FHY1 and FHL, and delayed the degradation of mutant phyA upon light exposure. Moreover, the in vivo formation of a phosphorylated phyA form was greatly affected by these mutations, while our data indicated that the abundance of this phosphorylated phyA form correlated well with the extent of phyA function, thus suggesting a pivotal role of the phosphorylated phyA in inducing the far-red light response. Taking these data together, our study reveals the important role of the hinge region of Arabidopsis phyA in regulating phyA phosphorylation and function, thus linking specific residues in the hinge region to the regulatory mechanisms of phyA phosphorylation.}, } @article {pmid30478059, year = {2018}, author = {Lees, AC}, title = {Interspecific conflict structures urban avian assemblages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12331-12333}, doi = {10.1073/pnas.1817912115}, pmid = {30478059}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; *Birds ; Cities ; }, } @article {pmid30478058, year = {2018}, author = {Smirnova, I and Kasho, V and Kaback, HR}, title = {Engineered occluded apo-intermediate of LacY.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12716-12721}, doi = {10.1073/pnas.1816267115}, pmid = {30478058}, issn = {1091-6490}, mesh = {Binding Sites ; Crystallography, X-Ray/methods ; Cytoplasm/metabolism ; Escherichia coli/metabolism ; Escherichia coli Proteins/*chemistry/*metabolism ; Galactosides/chemistry/metabolism ; Membrane Transport Proteins/chemistry/metabolism ; Monosaccharide Transport Proteins/*chemistry ; Periplasm/metabolism ; Symporters/*chemistry/metabolism ; }, abstract = {The lactose permease of Escherichia coli (LacY) utilizes an alternating access symport mechanism with multiple conformational intermediates, but only inward (cytoplasmic)- or outward (periplasmic)-open structures have been characterized by X-ray crystallography. It is demonstrated here with sugar-binding studies that cross-linking paired-Cys replacements across the closed cytoplasmic cavity stabilize an occluded conformer with an inaccessible sugar-binding site. In addition, a nanobody (Nb) that stabilizes a periplasmic-open conformer with an easily accessible sugar-binding site in WT LacY fails to cause the cytoplasmic cross-linked mutants to become accessible to galactoside, showing that the periplasmic cavity is closed. These results are consistent with tight association of the periplasmic ends in two pairs of helices containing clusters of small residues in the packing interface between N- and C-terminal six-helix bundles of the symporter. However, after reduction of the disulfide bond, the Nb markedly increases the rate of galactoside binding, indicating unrestricted access to the Nb epitope and the galactoside-binding site from the periplasm. The findings indicate that the cross-linked cytoplasmic double-Cys mutants resemble an occluded apo-intermediate in the transport cycle.}, } @article {pmid30478057, year = {2018}, author = {Peng, Q and Lu, S and Shi, Y and Pan, Y and Limsakul, P and Chernov, AV and Qiu, J and Chai, X and Shi, Y and Wang, P and Ji, Y and Li, YJ and Strongin, AY and Verkhusha, VV and Izpisua Belmonte, JC and Ren, B and Wang, Y and Chien, S and Wang, Y}, title = {Coordinated histone modifications and chromatin reorganization in a single cell revealed by FRET biosensors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11681-E11690}, doi = {10.1073/pnas.1811818115}, pmid = {30478057}, issn = {1091-6490}, support = {R01 GM125379/GM/NIGMS NIH HHS/United States ; R01 HL121365/HL/NHLBI NIH HHS/United States ; R21 CA209629/CA/NCI NIH HHS/United States ; R33 CA204704/CA/NCI NIH HHS/United States ; }, abstract = {The dramatic reorganization of chromatin during mitosis is perhaps one of the most fundamental of all cell processes. It remains unclear how epigenetic histone modifications, despite their crucial roles in regulating chromatin architectures, are dynamically coordinated with chromatin reorganization in controlling this process. We have developed and characterized biosensors with high sensitivity and specificity based on fluorescence resonance energy transfer (FRET). These biosensors were incorporated into nucleosomes to visualize histone H3 Lys-9 trimethylation (H3K9me3) and histone H3 Ser-10 phosphorylation (H3S10p) simultaneously in the same live cell. We observed an anticorrelated coupling in time between H3K9me3 and H3S10p in a single live cell during mitosis. A transient increase of H3S10p during mitosis is accompanied by a decrease of H3K9me3 that recovers before the restoration of H3S10p upon mitotic exit. We further showed that H3S10p is causatively critical for the decrease of H3K9me3 and the consequent reduction of heterochromatin structure, leading to the subsequent global chromatin reorganization and nuclear envelope dissolution as a cell enters mitosis. These results suggest a tight coupling of H3S10p and H3K9me3 dynamics in the regulation of heterochromatin dissolution before a global chromatin reorganization during mitosis.}, } @article {pmid30478056, year = {2018}, author = {Davis, GF}, title = {How to communicate large-scale social challenges: The problem of the disappearing American corporation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1805867115}, pmid = {30478056}, issn = {1091-6490}, abstract = {Social science has distinct advantages and challenges when it comes to communicating its findings to the public. Its topics are often highly accessible to the general public, yet its findings may be counterintuitive and politically contentious. Conveying recent changes in the organization of the American economy provides an illustration of the difficulties and opportunities for engaging the public. The declining number of public corporations in the United States is associated with a shrinking middle class, lower opportunities for upward mobility, and a fraying social safety net, with important implications for individuals and public policy. Attempting to convey this set of findings to a broad public has demonstrated that some strategies and communication channels work better than others, and that some online media are particularly effective.}, } @article {pmid30478055, year = {2018}, author = {Grossman, M and Bouville, F and Masania, K and Studart, AR}, title = {Quantifying the role of mineral bridges on the fracture resistance of nacre-like composites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12698-12703}, doi = {10.1073/pnas.1805094115}, pmid = {30478055}, issn = {1091-6490}, abstract = {The nacreous layer of mollusk shells holds design concepts that can effectively enhance the fracture resistance of lightweight brittle materials. Mineral bridges are known to increase the fracture resistance of nacre-inspired materials, but their role is difficult to quantify due to the lack of experimental systems where only this parameter is controllably varied. In this study, we fabricate tunable nacre-like composites that are used as a model to experimentally quantify the influence of the density of mineral bridges alone on the fracture properties of nacre-like architectures. The composites exhibit a brick-and-mortar architecture comprising highly aligned alumina platelets that are interconnected by titania mineral bridges and infiltrated by an epoxy organic phase. By combining experimental mechanical data with image analysis of such composite microstructures, an analytical model is put forward based on a simple balance of forces acting on an individual bridged platelet. Based on this model, we predict the flexural strength of the nacre-like composite to scale linearly with the density of mineral bridges, as long as the mineral interconnectivity is low enough to keep fracture in a platelet pullout mode. Increasing the mineral interconnectivity beyond this limit leads to platelet fracture and catastrophic failure of the composite. This structure-property correlation provides powerful quantitative guidelines for the design of lightweight brittle materials with enhanced fracture resistance. We illustrate this potential by fabricating nacre-like bulk composites with unparalleled flexural strength combined with noncatastrophic failure.}, } @article {pmid30478054, year = {2018}, author = {Williams, AM and Phaneuf, DJ and Barrett, MA and Su, JG}, title = {Short-term impact of PM2.5 on contemporaneous asthma medication use: Behavior and the value of pollution reductions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1805647115}, pmid = {30478054}, issn = {1091-6490}, abstract = {Asthma ranks among the most costly of chronic diseases, accounting for over $50 billion annually in direct medical expenditures in the United States. At the same time, evidence has accumulated that fine particulate matter pollution can exacerbate asthma symptoms and generate substantial economic costs. To measure these costs, we use a unique nationwide panel dataset tracking asthmatic individuals' use of rescue medication and their exposure to PM2.5 (particulate matter with an aerodynamic diameter of <2.5 μm) concentration between 2012 and 2017, to estimate the causal relationship between pollution and inhaler use. Our sample consists of individuals using an asthma digital health platform, which relies on a wireless sensor to track the place and time of inhaler use events, as well as regular nonevent location and time indicators. These data provide an accurate measurement of inhaler use and allow spatially and temporally resolute assignment of pollution exposure. Using a high-frequency research design and individual fixed effects, we find that a 1 μg/m3 (12%) increase in weekly exposure to PM2.5 increases weekly inhaler use by 0.82%. We also show that there is seasonal, regional, and income-based heterogeneity in this response. Using our response prediction, and an estimate from the literature on the willingness to pay to avoid asthma symptoms, we show that a nationwide 1 μg/m3 reduction in particulate matter concentration would generate nearly $350 million annually in economic benefits.}, } @article {pmid30478053, year = {2018}, author = {Qu, K and Glass, B and Doležal, M and Schur, FKM and Murciano, B and Rein, A and Rumlová, M and Ruml, T and Kräusslich, HG and Briggs, JAG}, title = {Structure and architecture of immature and mature murine leukemia virus capsids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11751-E11760}, doi = {10.1073/pnas.1811580115}, pmid = {30478053}, issn = {1091-6490}, support = {MC_UP_1201/16//Medical Research Council/United Kingdom ; }, abstract = {Retroviruses assemble and bud from infected cells in an immature form and require proteolytic maturation for infectivity. The CA (capsid) domains of the Gag polyproteins assemble a protein lattice as a truncated sphere in the immature virion. Proteolytic cleavage of Gag induces dramatic structural rearrangements; a subset of cleaved CA subsequently assembles into the mature core, whose architecture varies among retroviruses. Murine leukemia virus (MLV) is the prototypical γ-retrovirus and serves as the basis of retroviral vectors, but the structure of the MLV CA layer is unknown. Here we have combined X-ray crystallography with cryoelectron tomography to determine the structures of immature and mature MLV CA layers within authentic viral particles. This reveals the structural changes associated with maturation, and, by comparison with HIV-1, uncovers conserved and variable features. In contrast to HIV-1, most MLV CA is used for assembly of the mature core, which adopts variable, multilayered morphologies and does not form a closed structure. Unlike in HIV-1, there is similarity between protein-protein interfaces in the immature MLV CA layer and those in the mature CA layer, and structural maturation of MLV could be achieved through domain rotations that largely maintain hexameric interactions. Nevertheless, the dramatic architectural change on maturation indicates that extensive disassembly and reassembly are required for mature core growth. The core morphology suggests that wrapping of the genome in CA sheets may be sufficient to protect the MLV ribonucleoprotein during cell entry.}, } @article {pmid30478052, year = {2018}, author = {Ma, C and Tian, X and Kim, JP and Xie, D and Ao, X and Shan, D and Lin, Q and Hudock, MR and Bai, X and Yang, J}, title = {Citrate-based materials fuel human stem cells by metabonegenic regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11741-E11750}, doi = {10.1073/pnas.1813000115}, pmid = {30478052}, issn = {1091-6490}, support = {R01 AR072731/AR/NIAMS NIH HHS/United States ; R01 CA182670/CA/NCI NIH HHS/United States ; R21 EB024829/EB/NIBIB NIH HHS/United States ; }, abstract = {A comprehensive understanding of the key microenvironmental signals regulating bone regeneration is pivotal for the effective design of bioinspired orthopedic materials. Here, we identified citrate as an osteopromotive factor and revealed its metabonegenic role in mediating citrate metabolism and its downstream effects on the osteogenic differentiation of human mesenchymal stem cells (hMSCs). Our studies show that extracellular citrate uptake through solute carrier family 13, member 5 (SLC13a5) supports osteogenic differentiation via regulation of energy-producing metabolic pathways, leading to elevated cell energy status that fuels the high metabolic demands of hMSC osteodifferentiation. We next identified citrate and phosphoserine (PSer) as a synergistic pair in polymeric design, exhibiting concerted action not only in metabonegenic potential for orthopedic regeneration but also in facile reactivity in a fluorescent system for materials tracking and imaging. We designed a citrate/phosphoserine-based photoluminescent biodegradable polymer (BPLP-PSer), which was fabricated into BPLP-PSer/hydroxyapatite composite microparticulate scaffolds that demonstrated significant improvements in bone regeneration and tissue response in rat femoral-condyle and cranial-defect models. We believe that the present study may inspire the development of new generations of biomimetic biomaterials that better recapitulate the metabolic microenvironments of stem cells to meet the dynamic needs of cellular growth, differentiation, and maturation for use in tissue engineering.}, } @article {pmid30478051, year = {2018}, author = {Sang, B and Zhang, YY and Guo, ST and Kong, LF and Cheng, Q and Liu, GZ and Thorne, RF and Zhang, XD and Jin, L and Wu, M}, title = {Dual functions for OVAAL in initiation of RAF/MEK/ERK prosurvival signals and evasion of p27-mediated cellular senescence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11661-E11670}, doi = {10.1073/pnas.1805950115}, pmid = {30478051}, issn = {1091-6490}, abstract = {Long noncoding RNAs (lncRNAs) function through a diverse array of mechanisms that are not presently fully understood. Here, we sought to find lncRNAs differentially regulated in cancer cells resistant to either TNF-related apoptosis-inducing ligand (TRAIL) or the Mcl-1 inhibitor UMI-77, agents that act through the extrinsic and intrinsic apoptotic pathways, respectively. This work identified a commonly up-regulated lncRNA, ovarian adenocarcinoma-amplified lncRNA (OVAAL), that conferred apoptotic resistance in multiple cancer types. Analysis of clinical samples revealed OVAAL expression was significantly increased in colorectal cancers and melanoma in comparison to the corresponding normal tissues. Functional investigations showed that OVAAL depletion significantly inhibited cancer cell proliferation and retarded tumor xenograft growth. Mechanically, OVAAL physically interacted with serine/threonine-protein kinase 3 (STK3), which, in turn, enhanced the binding between STK3 and Raf-1. The ternary complex OVAAL/STK3/Raf-1 enhanced the activation of the RAF protooncogene serine/threonine-protein kinase (RAF)/mitogen-activated protein kinase kinase 1 (MEK)/ERK signaling cascade, thus promoting c-Myc-mediated cell proliferation and Mcl-1-mediated cell survival. On the other hand, depletion of OVAAL triggered cellular senescence through polypyrimidine tract-binding protein 1 (PTBP1)-mediated p27 expression, which was regulated by competitive binding between OVAAL and p27 mRNA to PTBP1. Additionally, c-Myc was demonstrated to drive OVAAL transcription, indicating a positive feedback loop between c-Myc and OVAAL in controlling tumor growth. Taken together, these results reveal that OVAAL contributes to the survival of cancer cells through dual mechanisms controlling RAF/MEK/ERK signaling and p27-mediated cell senescence.}, } @article {pmid30478050, year = {2018}, author = {Iyengar, S and Massey, DS}, title = {Scientific communication in a post-truth society.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1805868115}, pmid = {30478050}, issn = {1091-6490}, abstract = {Within the scientific community, much attention has focused on improving communications between scientists, policy makers, and the public. To date, efforts have centered on improving the content, accessibility, and delivery of scientific communications. Here we argue that in the current political and media environment faulty communication is no longer the core of the problem. Distrust in the scientific enterprise and misperceptions of scientific knowledge increasingly stem less from problems of communication and more from the widespread dissemination of misleading and biased information. We describe the profound structural shifts in the media environment that have occurred in recent decades and their connection to public policy decisions and technological changes. We explain how these shifts have enabled unscrupulous actors with ulterior motives increasingly to circulate fake news, misinformation, and disinformation with the help of trolls, bots, and respondent-driven algorithms. We document the high degree of partisan animosity, implicit ideological bias, political polarization, and politically motivated reasoning that now prevail in the public sphere and offer an actual example of how clearly stated scientific conclusions can be systematically perverted in the media through an internet-based campaign of disinformation and misinformation. We suggest that, in addition to attending to the clarity of their communications, scientists must also develop online strategies to counteract campaigns of misinformation and disinformation that will inevitably follow the release of findings threatening to partisans on either end of the political spectrum.}, } @article {pmid30478049, year = {2018}, author = {}, title = {Retraction for Baradaran-Heravi et al., Gentamicin B1 is a minor gentamicin component with major nonsense mutation suppression activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11885}, doi = {10.1073/pnas.1818172115}, pmid = {30478049}, issn = {1091-6490}, } @article {pmid30478048, year = {2018}, author = {Xue, B and Leibler, S}, title = {Benefits of phenotypic plasticity for population growth in varying environments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12745-12750}, doi = {10.1073/pnas.1813447115}, pmid = {30478048}, issn = {1091-6490}, mesh = {Adaptation, Physiological/*physiology ; Animals ; Biological Evolution ; Cues ; Environment ; Life ; Phenotype ; Population Growth ; }, abstract = {Phenotypic plasticity refers to the capacity of the same organisms to exhibit different characteristics under varied environmental conditions. A plastic developmental program allows organisms to sense environmental cues in early stages of life and express phenotypes that are better fitted to environments encountered later in life. This is often considered an adaptive strategy for living in varying environments as long as the plastic response is sufficiently fast, is accurate, and is not too costly. However, despite direct costs of maintaining plasticity and producing phenotypes, a fundamental constraint on the benefit of phenotypic plasticity comes from the predictability of the future environment based on the environmental cues received during development. Here, we analyze a model of plastic development and derive the limits within which this strategy can promote population growth. An explicit expression for the long-term growth rate of a developmentally plastic population is found, which can be decomposed into several easily interpretable terms, representing the benefits and the limitations of phenotypic plasticity as an adaptation strategy. This growth rate decomposition has a remarkably similar form to the expressions previously obtained for the bet-hedging strategy, in which a population randomly diversifies into coexisting subgroups with different phenotypes, implying that those evolutionary strategies may be unified under a common general framework.}, } @article {pmid30478047, year = {2018}, author = {Ditas, J and Ma, N and Zhang, Y and Assmann, D and Neumaier, M and Riede, H and Karu, E and Williams, J and Scharffe, D and Wang, Q and Saturno, J and Schwarz, JP and Katich, JM and McMeeking, GR and Zahn, A and Hermann, M and Brenninkmeijer, CAM and Andreae, MO and Pöschl, U and Su, H and Cheng, Y}, title = {Strong impact of wildfires on the abundance and aging of black carbon in the lowermost stratosphere.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11595-E11603}, doi = {10.1073/pnas.1806868115}, pmid = {30478047}, issn = {1091-6490}, abstract = {Wildfires inject large amounts of black carbon (BC) particles into the atmosphere, which can reach the lowermost stratosphere (LMS) and cause strong radiative forcing. During a 14-month period of observations on board a passenger aircraft flying between Europe and North America, we found frequent and widespread biomass burning (BB) plumes, influencing 16 of 160 flight hours in the LMS. The average BC mass concentrations in these plumes (∼140 ng·m-3, standard temperature and pressure) were over 20 times higher than the background concentration (∼6 ng·m-3) with more than 100-fold enhanced peak values (up to ∼720 ng·m-3). In the LMS, nearly all BC particles were covered with a thick coating. The average mass equivalent diameter of the BC particle cores was ∼120 nm with a mean coating thickness of ∼150 nm in the BB plume and ∼90 nm with a coating of ∼125 nm in the background. In a BB plume that was encountered twice, we also found a high diameter growth rate of ∼1 nm·h-1 due to the BC particle coatings. The observed high concentrations and thick coatings of BC particles demonstrate that wildfires can induce strong local heating in the LMS and may have a significant influence on the regional radiative forcing of climate.}, } @article {pmid30478046, year = {2018}, author = {Lovat, F and Fassan, M and Sacchi, D and Ranganathan, P and Palamarchuk, A and Bill, M and Karunasiri, M and Gasparini, P and Nigita, G and Distefano, R and Veneziano, D and Dorrance, AM and Garzon, R and Croce, CM}, title = {Knockout of both miR-15/16 loci induces acute myeloid leukemia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13069-13074}, doi = {10.1073/pnas.1814980115}, pmid = {30478046}, issn = {1091-6490}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; R35 CA197706/CA/NCI NIH HHS/United States ; }, abstract = {MicroRNAs (miRNAs) have been extensively reported to be associated with hematological malignancies. The loss of miR-15a/16-1 at chromosome 13q14 is a hallmark of most of human chronic lymphocytic leukemia (CLL). Deletion of murine miR-15a/16-1 and miR-15b/16-2 has been demonstrated to promote B cell malignancies. Here, we evaluate the biological role of miR-15/16 clusters, crossbreeding miR-15a/16-1 and miR-15b/16-2 knockout mice. Unexpectedly, the complete deletion of both clusters promoted myeloproliferative disorders in the majority of the mice by the age of 5 months with a penetrance of 70%. These mice showed a significant enlargement of spleen and abnormal swelling of lymph nodes. Flow cytometry characterization demonstrated an expanded CD11b/Gr-1 double-positive myeloid population both in spleen and in bone marrow. The transplantation of splenocytes harvested from double-KO mice into wild-type recipient mice resulted in the development of myeloproliferative disorders, as observed in the donors. In vivo, miR-15/16 cluster deletion up-regulated the expression of Cyclin D1, Cyclin D2, and Bcl-2. Taken together, our findings identify a driver oncogenic role for miR-15/16 cluster deletion in different leukocytic cell lineages.}, } @article {pmid30478045, year = {2018}, author = {Zhao, R and Kennedy, K and De Blas, GA and Orta, G and Pavarotti, MA and Arias, RJ and de la Vega-Beltrán, JL and Li, Q and Dai, H and Perozo, E and Mayorga, LS and Darszon, A and Goldstein, SAN}, title = {Role of human Hv1 channels in sperm capacitation and white blood cell respiratory burst established by a designed peptide inhibitor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11847-E11856}, doi = {10.1073/pnas.1816189115}, pmid = {30478045}, issn = {1091-6490}, support = {R01 GM057846/GM/NIGMS NIH HHS/United States ; R01 GM111716/GM/NIGMS NIH HHS/United States ; }, abstract = {Using a de novo peptide inhibitor, Corza6 (C6), we demonstrate that the human voltage-gated proton channel (hHv1) is the main pathway for H+ efflux that allows capacitation in sperm and permits sustained reactive oxygen species (ROS) production in white blood cells (WBCs). C6 was identified by a phage-display strategy whereby ∼1 million novel peptides were fabricated on an inhibitor cysteine knot (ICK) scaffold and sorting on purified hHv1 protein. Two C6 peptides bind to each dimeric channel, one on the S3-S4 loop of each voltage sensor domain (VSD). Binding is cooperative with an equilibrium affinity (Kd) of ∼1 nM at -50 mV. As expected for a VSD-directed toxin, C6 inhibits by shifting hHv1 activation to more positive voltages, slowing opening and speeding closure, effects that diminish with membrane depolarization.}, } @article {pmid30478044, year = {2018}, author = {}, title = {Correction for Yoon et al., Control of movement vigor and decision making during foraging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11884}, doi = {10.1073/pnas.1818731115}, pmid = {30478044}, issn = {1091-6490}, } @article {pmid30478043, year = {2018}, author = {Johnson, KP and Dietrich, CH and Friedrich, F and Beutel, RG and Wipfler, B and Peters, RS and Allen, JM and Petersen, M and Donath, A and Walden, KKO and Kozlov, AM and Podsiadlowski, L and Mayer, C and Meusemann, K and Vasilikopoulos, A and Waterhouse, RM and Cameron, SL and Weirauch, C and Swanson, DR and Percy, DM and Hardy, NB and Terry, I and Liu, S and Zhou, X and Misof, B and Robertson, HM and Yoshizawa, K}, title = {Phylogenomics and the evolution of hemipteroid insects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12775-12780}, doi = {10.1073/pnas.1815820115}, pmid = {30478043}, issn = {1091-6490}, mesh = {Animals ; Calibration ; Ecosystem ; Fossils ; Genome, Mitochondrial/genetics ; Insecta/*genetics ; Phylogeny ; }, abstract = {Hemipteroid insects (Paraneoptera), with over 10% of all known insect diversity, are a major component of terrestrial and aquatic ecosystems. Previous phylogenetic analyses have not consistently resolved the relationships among major hemipteroid lineages. We provide maximum likelihood-based phylogenomic analyses of a taxonomically comprehensive dataset comprising sequences of 2,395 single-copy, protein-coding genes for 193 samples of hemipteroid insects and outgroups. These analyses yield a well-supported phylogeny for hemipteroid insects. Monophyly of each of the three hemipteroid orders (Psocodea, Thysanoptera, and Hemiptera) is strongly supported, as are most relationships among suborders and families. Thysanoptera (thrips) is strongly supported as sister to Hemiptera. However, as in a recent large-scale analysis sampling all insect orders, trees from our data matrices support Psocodea (bark lice and parasitic lice) as the sister group to the holometabolous insects (those with complete metamorphosis). In contrast, four-cluster likelihood mapping of these data does not support this result. A molecular dating analysis using 23 fossil calibration points suggests hemipteroid insects began diversifying before the Carboniferous, over 365 million years ago. We also explore implications for understanding the timing of diversification, the evolution of morphological traits, and the evolution of mitochondrial genome organization. These results provide a phylogenetic framework for future studies of the group.}, } @article {pmid30478042, year = {2018}, author = {MacPherson, Q and Beltran, B and Spakowitz, AJ}, title = {Bottom-up modeling of chromatin segregation due to epigenetic modifications.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12739-12744}, doi = {10.1073/pnas.1812268115}, pmid = {30478042}, issn = {1091-6490}, support = {T32 GM008294/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromatin/*genetics ; Chromosomal Proteins, Non-Histone/genetics ; Chromosome Segregation/*genetics ; Epigenesis, Genetic/*genetics ; Euchromatin/genetics ; Heterochromatin/genetics ; Histones/genetics ; Humans ; Monte Carlo Method ; Nucleosomes/genetics ; Probability ; }, abstract = {We use a chromosome-scale simulation to show that the preferential binding of heterochromatin protein 1 (HP1) to regions high in histone methylation (specifically H3K9me3) results in phase segregation and reproduces features of the observed Hi-C contact map. Specifically, we perform Monte Carlo simulations with one computational bead per nucleosome and an H3K9me3 pattern based on published ChIP-seq signals. We implement a binding model in which HP1 preferentially binds to trimethylated histone tails and then oligomerizes to bridge together nucleosomes. We observe a phase reminiscent of heterochromatin-dense and high in H3K9me3-and another reminiscent of euchromatin-less dense and lacking H3K9me3. This segregation results in a plaid contact probability map that matches the general shape and position of published Hi-C data. Analysis suggests that a roughly 20-kb segment of H3K9me3 enrichment is required to drive segregation into the heterochromatic phase.}, } @article {pmid30478041, year = {2018}, author = {Namouchi, A and Guellil, M and Kersten, O and Hänsch, S and Ottoni, C and Schmid, BV and Pacciani, E and Quaglia, L and Vermunt, M and Bauer, EL and Derrick, M and Jensen, AØ and Kacki, S and Cohn, SK and Stenseth, NC and Bramanti, B}, title = {Integrative approach using Yersinia pestis genomes to revisit the historical landscape of plague during the Medieval Period.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11790-E11797}, doi = {10.1073/pnas.1812865115}, pmid = {30478041}, issn = {1091-6490}, abstract = {Over the last few years, genomic studies on Yersinia pestis, the causative agent of all known plague epidemics, have considerably increased in numbers, spanning a period of about 5,000 y. Nonetheless, questions concerning historical reservoirs and routes of transmission remain open. Here, we present and describe five genomes from the second half of the 14th century and reconstruct the evolutionary history of Y. pestis by reanalyzing previously published genomes and by building a comprehensive phylogeny focused on strains attributed to the Second Plague Pandemic (14th to 18th century). Corroborated by historical and ecological evidence, the presented phylogeny, which includes our Y. pestis genomes, could support the hypothesis of an entry of plague into Western European ports through distinct waves of introduction during the Medieval Period, possibly by means of fur trade routes, as well as the recirculation of plague within the human population via trade routes and human movement.}, } @article {pmid30478040, year = {2018}, author = {Nauer, PA and Hutley, LB and Arndt, SK}, title = {Termite mounds mitigate half of termite methane emissions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {52}, pages = {13306-13311}, doi = {10.1073/pnas.1809790115}, pmid = {30478040}, issn = {1091-6490}, abstract = {Termites are responsible for ∼1 to 3% of global methane (CH4) emissions. However, estimates of global termite CH4 emissions span two orders of magnitude, suggesting that fundamental knowledge of CH4 turnover processes in termite colonies is missing. In particular, there is little reliable information on the extent and location of microbial CH4 oxidation in termite mounds. Here, we use a one-box model to unify three independent field methods-a gas-tracer test, an inhibitor approach, and a stable-isotope technique-and quantify CH4 production, oxidation, and transport in three North Australian termite species with different feeding habits and mound architectures. We present systematic in situ evidence of widespread CH4 oxidation in termite mounds, with 20 to 80% of termite-produced CH4 being mitigated before emission to the atmosphere. Furthermore, closing the CH4 mass balance in mounds allows us to estimate in situ termite biomass from CH4 turnover, with mean biomass ranging between 22 and 86 g of termites per kilogram of mound for the three species. Field tests with excavated mounds show that the predominant location of CH4 oxidation is either in the mound material or the soil beneath and is related to species-specific mound porosities. Regardless of termite species, however, our data and model suggest that the fraction of oxidized CH4 (fox) remains well buffered due to links among consumption, oxidation, and transport processes via mound CH4 concentration. The mean fox of 0.50 ± 0.11 (95% CI) from in situ measurements therefore presents a valid oxidation factor for future global estimates of termite CH4 emissions.}, } @article {pmid30478039, year = {2018}, author = {Sonke, JE and Teisserenc, R and Heimbürger-Boavida, LE and Petrova, MV and Marusczak, N and Le Dantec, T and Chupakov, AV and Li, C and Thackray, CP and Sunderland, EM and Tananaev, N and Pokrovsky, OS}, title = {Eurasian river spring flood observations support net Arctic Ocean mercury export to the atmosphere and Atlantic Ocean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11586-E11594}, doi = {10.1073/pnas.1811957115}, pmid = {30478039}, issn = {1091-6490}, abstract = {Midlatitude anthropogenic mercury (Hg) emissions and discharge reach the Arctic Ocean (AO) by atmospheric and oceanic transport. Recent studies suggest that Arctic river Hg inputs have been a potentially overlooked source of Hg to the AO. Observations on Hg in Eurasian rivers, which represent 80% of freshwater inputs to the AO, are quasi-inexistent, however, putting firm understanding of the Arctic Hg cycle on hold. Here, we present comprehensive seasonal observations on dissolved Hg (DHg) and particulate Hg (PHg) concentrations and fluxes for two large Eurasian rivers, the Yenisei and the Severnaya Dvina. We find large DHg and PHg fluxes during the spring flood, followed by a second pulse during the fall flood. We observe well-defined water vs. Hg runoff relationships for Eurasian and North American Hg fluxes to the AO and for Canadian Hg fluxes into the larger Hudson Bay area. Extrapolation to pan-Arctic rivers and watersheds gives a total Hg river flux to the AO of 44 ± 4 Mg per year (1σ), in agreement with the recent model-based estimates of 16 to 46 Mg per year and Hg/dissolved organic carbon (DOC) observation-based estimate of 50 Mg per year. The river Hg budget, together with recent observations on tundra Hg uptake and AO Hg dynamics, provide a consistent view of the Arctic Hg cycle in which continental ecosystems traffic anthropogenic Hg emissions to the AO via rivers, and the AO exports Hg to the atmosphere, to the Atlantic Ocean, and to AO marine sediments.}, } @article {pmid30478038, year = {2018}, author = {Wang, Y and Cho, C and Williams, J and Smallwood, PM and Zhang, C and Junge, HJ and Nathans, J}, title = {Interplay of the Norrin and Wnt7a/Wnt7b signaling systems in blood-brain barrier and blood-retina barrier development and maintenance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11827-E11836}, doi = {10.1073/pnas.1813217115}, pmid = {30478038}, issn = {1091-6490}, support = {R01 EY018637/EY/NEI NIH HHS/United States ; R01 EY024261/EY/NEI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {β-Catenin signaling controls the development and maintenance of the blood-brain barrier (BBB) and the blood-retina barrier (BRB), but the division of labor and degree of redundancy between the two principal ligand-receptor systems-the Norrin and Wnt7a/Wnt7b systems-are incompletely defined. Here, we present a loss-of-function genetic analysis of postnatal BBB and BRB maintenance in mice that shows striking threshold and partial redundancy effects. In particular, the combined loss of Wnt7a and Norrin or Wnt7a and Frizzled4 (Fz4) leads to anatomically localized BBB defects that are far more severe than observed with loss of Wnt7a, Norrin, or Fz4 alone. In the cerebellum, selective loss of Wnt7a in glia combined with ubiquitous loss of Norrin recapitulates the phenotype observed with ubiquitous loss of both Wnt7a and Norrin, implying that glia are the source of Wnt7a in the cerebellum. Tspan12, a coactivator of Norrin signaling in the retina, is also active in BBB maintenance but is less potent than Norrin, consistent with a model in which Tspan12 enhances the amplitude of the Norrin signal in vascular endothelial cells. Finally, in the context of a partially impaired Norrin system, the retina reveals a small contribution to BRB development from the Wnt7a/Wnt7b system. Taken together, these experiments define the extent of CNS region-specific cooperation for several components of the Norrin and Wnt7a/Wnt7b systems, and they reveal substantial regional heterogeneity in the extent to which partially redundant ligands, receptors, and coactivators maintain the BBB and BRB.}, } @article {pmid30478037, year = {2018}, author = {Kotlobay, AA and Sarkisyan, KS and Mokrushina, YA and Marcet-Houben, M and Serebrovskaya, EO and Markina, NM and Gonzalez Somermeyer, L and Gorokhovatsky, AY and Vvedensky, A and Purtov, KV and Petushkov, VN and Rodionova, NS and Chepurnyh, TV and Fakhranurova, LI and Guglya, EB and Ziganshin, R and Tsarkova, AS and Kaskova, ZM and Shender, V and Abakumov, M and Abakumova, TO and Povolotskaya, IS and Eroshkin, FM and Zaraisky, AG and Mishin, AS and Dolgov, SV and Mitiouchkina, TY and Kopantzev, EP and Waldenmaier, HE and Oliveira, AG and Oba, Y and Barsova, E and Bogdanova, EA and Gabaldón, T and Stevani, CV and Lukyanov, S and Smirnov, IV and Gitelson, JI and Kondrashov, FA and Yampolsky, IV}, title = {Genetically encodable bioluminescent system from fungi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12728-12732}, doi = {10.1073/pnas.1803615115}, pmid = {30478037}, issn = {1091-6490}, support = {310325//European Research Council/International ; 335980//European Research Council/International ; }, mesh = {Amino Acid Sequence ; Animals ; Biosynthetic Pathways/genetics ; Caffeic Acids ; Cell Line ; Cell Line, Tumor ; Female ; Fungi/*genetics ; Gene Duplication/genetics ; HEK293 Cells ; HeLa Cells ; Humans ; Luminescent Proteins/*genetics ; Mice ; Mice, Inbred BALB C ; Sequence Alignment ; Xenopus laevis ; }, abstract = {Bioluminescence is found across the entire tree of life, conferring a spectacular set of visually oriented functions from attracting mates to scaring off predators. Half a dozen different luciferins, molecules that emit light when enzymatically oxidized, are known. However, just one biochemical pathway for luciferin biosynthesis has been described in full, which is found only in bacteria. Here, we report identification of the fungal luciferase and three other key enzymes that together form the biosynthetic cycle of the fungal luciferin from caffeic acid, a simple and widespread metabolite. Introduction of the identified genes into the genome of the yeast Pichia pastoris along with caffeic acid biosynthesis genes resulted in a strain that is autoluminescent in standard media. We analyzed evolution of the enzymes of the luciferin biosynthesis cycle and found that fungal bioluminescence emerged through a series of events that included two independent gene duplications. The retention of the duplicated enzymes of the luciferin pathway in nonluminescent fungi shows that the gene duplication was followed by functional sequence divergence of enzymes of at least one gene in the biosynthetic pathway and suggests that the evolution of fungal bioluminescence proceeded through several closely related stepping stone nonluminescent biochemical reactions with adaptive roles. The availability of a complete eukaryotic luciferin biosynthesis pathway provides several applications in biomedicine and bioengineering.}, } @article {pmid30478036, year = {2018}, author = {Luo, S and Valencia, CA and Zhang, J and Lee, NC and Slone, J and Gui, B and Wang, X and Li, Z and Dell, S and Brown, J and Chen, SM and Chien, YH and Hwu, WL and Fan, PC and Wong, LJ and Atwal, PS and Huang, T}, title = {Biparental Inheritance of Mitochondrial DNA in Humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {13039-13044}, doi = {10.1073/pnas.1810946115}, pmid = {30478036}, issn = {1091-6490}, abstract = {Although there has been considerable debate about whether paternal mitochondrial DNA (mtDNA) transmission may coexist with maternal transmission of mtDNA, it is generally believed that mitochondria and mtDNA are exclusively maternally inherited in humans. Here, we identified three unrelated multigeneration families with a high level of mtDNA heteroplasmy (ranging from 24 to 76%) in a total of 17 individuals. Heteroplasmy of mtDNA was independently examined by high-depth whole mtDNA sequencing analysis in our research laboratory and in two Clinical Laboratory Improvement Amendments and College of American Pathologists-accredited laboratories using multiple approaches. A comprehensive exploration of mtDNA segregation in these families shows biparental mtDNA transmission with an autosomal dominantlike inheritance mode. Our results suggest that, although the central dogma of maternal inheritance of mtDNA remains valid, there are some exceptional cases where paternal mtDNA could be passed to the offspring. Elucidating the molecular mechanism for this unusual mode of inheritance will provide new insights into how mtDNA is passed on from parent to offspring and may even lead to the development of new avenues for the therapeutic treatment for pathogenic mtDNA transmission.}, } @article {pmid30477958, year = {2019}, author = {Singh, HR and Ostwal, YB}, title = {Post-Translational Modification, Phase Separation, and Robust Gene Transcription.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {89-92}, doi = {10.1016/j.tig.2018.11.002}, pmid = {30477958}, issn = {0168-9525}, abstract = {A few recent reports reveal fundamental new insights into the intricate regulatory mechanisms that govern RNA polymerase II (Pol II)-mediated gene transcription. Whereas a histidine-rich domain (HRD) triggers phase separation, promoting transcription elongation, a phosphatase switch promotes transcription termination. A paradigm that might govern the underlying mechanisms leading to robust gene transcription is now starting to emerge.}, } @article {pmid30477908, year = {2018}, author = {Aguilar, C and Mano, M and Eulalio, A}, title = {MicroRNAs at the Host-Bacteria Interface: Host Defense or Bacterial Offense.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.10.011}, pmid = {30477908}, issn = {1878-4380}, abstract = {MicroRNAs are a class of small noncoding RNAs that act as major post-transcriptional regulators of gene expression. They are currently recognized for their important role in the intricate interaction between host and bacterial pathogens, either as part of the host immune response to neutralize infection, or as a molecular strategy employed by bacteria to hijack host pathways for their own benefit. Here, we summarize recent advances on the function of miRNAs during infection of mammalian hosts by bacterial pathogens, highlighting key cellular pathways. In addition, we discuss emerging themes in this field, including the participation of miRNAs in host-microbiota crosstalk and cell-to-cell communication.}, } @article {pmid30477758, year = {2019}, author = {Morgan, ER and Aziz, NA and Blanchard, A and Charlier, J and Charvet, C and Claerebout, E and Geldhof, P and Greer, AW and Hertzberg, H and Hodgkinson, J and Höglund, J and Hoste, H and Kaplan, RM and Martínez-Valladares, M and Mitchell, S and Ploeger, HW and Rinaldi, L and von Samson-Himmelstjerna, G and Sotiraki, S and Schnyder, M and Skuce, P and Bartley, D and Kenyon, F and Thamsborg, SM and Vineer, HR and de Waal, T and Williams, AR and van Wyk, JA and Vercruysse, J}, title = {100 Questions in Livestock Helminthology Research.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {52-71}, doi = {10.1016/j.pt.2018.10.006}, pmid = {30477758}, issn = {1471-5007}, abstract = {An elicitation exercise was conducted to collect and identify pressing questions concerning the study of helminths in livestock, to help guide research priorities. Questions were invited from the research community in an inclusive way. Of 385 questions submitted, 100 were chosen by online vote, with priority given to open questions in important areas that are specific enough to permit investigation within a focused project or programme of research. The final list of questions was divided into ten themes. We present the questions and set them briefly in the context of the current state of knowledge. Although subjective, the results provide a snapshot of current concerns and perceived priorities in the field of livestock helminthology, and we hope that they will stimulate ongoing or new research efforts.}, } @article {pmid30477588, year = {2018}, author = {Nacher, M and Huber, F and Adriouch, L and Djossou, F and Adenis, A and Couppié, P}, title = {Temporal trend of the proportion of patients presenting with advanced HIV in French Guiana: stuck on the asymptote?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {831}, pmid = {30477588}, issn = {1756-0500}, abstract = {OBJECTIVE: In French Guiana, the French territory with the most preoccupying HIV epidemic, there have been great efforts to intensify and diversify HIV testing strategies. The aim of the present study was to review the temporal trends of patients diagnosed with advanced HIV disease in French Guiana. Data trends from the HIV cohort of French Guiana between 1996 and 2016 were thus analyzed.

RESULTS: The proportion of patients diagnosed with advanced disease did not decline over time. Males had lower CD4 counts at the time of diagnosis and there was a plateau for both males (around 40%) and females (around 25%) with no apparent reduction of the proportion of advanced disease. Older age groups and migrants presented more often with advanced disease. By contrast, the proportion of patients diagnosed with stage B and C disease declined over time and the CD4 count at antiretroviral initiation and the CD4 nadir increased over time. Despite some progress, the group of patients with advanced disease reached a plateau around 30% suggesting this particular group still has epidemiological importance in driving the epidemic and in fueling morbidity and mortality, and thus remains a challenge for testing strategies.}, } @article {pmid30477584, year = {2018}, author = {Singh, RF and Kelly, P and Tam, A and Bronner, J and Morello, CM and Hirsch, JD}, title = {Evaluation of a short, interactive diabetes self-management program by pharmacists for type 2 diabetes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {828}, pmid = {30477584}, issn = {1756-0500}, support = {TL1 TR000098-04//National Institutes of Health/ ; }, abstract = {OBJECTIVE: Numerous barriers prevent patients with type 2 diabetes (T2D) from completing a diabetes self-management program. We investigated whether patients with T2D exhibited improved clinical outcomes after attending a relatively short, interactive diabetes self-management program conducted by pharmacist diabetes educators, compared to a physician's usual care.

RESULTS: We retrospectively analyzed the data of adults with T2D who attended a diabetes self-management program (≥ 1 group meeting or individual appointment followed by a telephone interview from a pharmacist diabetes educator between May 2010 and Dec. 2012; n = 513) and compared their outcomes with those of T2D patients who received only their physician's usual care (n = 857). Each patient's A1C was assessed at baseline, 3 months, and 6 months post-intervention. The mean [SD] reduction in A1C percentage points in the T2D patients was significantly greater in the diabetes self-management program group compared to the physician's usual care group at both 3 months (- 0.8% [1.5] vs. - 0.2% [0.9], p < 0.001) and 6 months post-intervention (- 0.6% [1.3] vs. - 0.2% [1.1], p < 0.001). T2D patients significantly improved their glycemic control within 3-6 months of attending the diabetes self-management program compared to patients who only received their physician's usual care.}, } @article {pmid30477580, year = {2018}, author = {Ballot, DE and Ramdin, T and White, DA and Lipman, J}, title = {A comparison between raw and predicted mortality in a paediatric intensive care unit in South Africa.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {829}, pmid = {30477580}, issn = {1756-0500}, abstract = {OBJECTIVE: Paediatric intensive care resources are limited in sub-Saharan Africa. The mortality rate in a combined Paediatric/Neonatal Intensive Care Unit in Johannesburg, South Africa was almost double that in a dedicated paediatric intensive care unit in the same country. This study aimed to compare the raw mortality rate with that predicted with the Paediatric Index of Mortality (version 3), by doing a retrospective analysis of an existing database.

RESULTS: A total of 530 patients admitted to the intensive care unit between 1 January 2015 and 31 December 2017 were included. The raw mortality rate was 27.1% and the predicted mortality rate was 27.0% (p = 0.971). Cardiac arrest during ICU admission (p < 0.001), non-reactive pupils (0.035), inotropic support (p < 0.001) and renal disease (p = 0.002) were all associated with an increased risk of mortality. These findings indicate that the high mortality rate is due to the severity of illness in the patients that are admitted. It also indicates that the quality of care delivered is acceptable.}, } @article {pmid30477577, year = {2018}, author = {Dewe, G and Steyaert, A and De Kock, M and Lois, F and Reding, R and Forget, P}, title = {Pain management in living related adult donor hepatectomy: feasibility of an evidence-based protocol in 100 consecutive donors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {834}, pmid = {30477577}, issn = {1756-0500}, abstract = {OBJECTIVE: Living donor hepatectomy (LDH) has important consequences in terms of acute and chronic pain. We proposed an anesthetic protocol based on the best currently available evidence. We report the results of this protocol's application.

RESULTS: We performed a retrospective descriptive study of 100 consecutive donors undergoing LDH. The protocol included standardized information provided by the anesthetist, pharmacological anxiolysis and preventive analgesia. Specifically, pregabalin premedication (opioid-free) intravenous anesthesia (with clonidine, ketamine, magnesium sulphate and ketorolac) and epidural analgesia were proposed. Postoperative follow-up was conducted by the Postoperative Pain Service. This analysis included 100 patients (53 women, 47 men, median age 32.7 years old [28.4-37.3]), operated by xypho-umbilical laparotomy. All elements of our anesthetic protocol were applied in over 75% of patients, except for the preoperative consultation with a senior anesthesiologist (55%). The median number of applied item was 7 [interquartile range, IQR 5-7]. Median postoperative pain scores were, at rest and at mobilization respectively 3 [IQR 2-4] and 6 [IQR 4.5-7] on day 1; 2 [IQR 1-3] and 5 [IQR 3-6] on day 2; and 2 [IQR 0-3] and 4 [IQR 3-5] on day 3. In conclusion, LDH leads to severe acute pain. Despite the proposal of a multimodal evidence-based protocol, its applicancy was not uniform and the pain scores remained relatively high.}, } @article {pmid30477571, year = {2018}, author = {Wilson, D and Breen, L and Lord, JM and Sapey, E}, title = {The challenges of muscle biopsy in a community based geriatric population.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {830}, pmid = {30477571}, issn = {1756-0500}, abstract = {OBJECTIVES: To describe the difficulties of obtaining muscle samples using a Bergstrom needle technique in a frail older adult population. The data were obtained from a study primarily investigating immunosenescence in frailty. An intended research technique was skeletal muscle biopsy in a small subset of participants to investigate muscle morphology and local inflammatory factors.

RESULTS: Forty healthy older adults and 37 frail older adults were considered for a Bergstrom needle muscle biopsy. Of these, 17.5% of healthy older adults and 94.6% of the frail older adults had single or multiple participant factors resulting in a contra-indication to muscle biopsy. 40.7% of healthy older female participants were at risk of a failed muscle biopsy due to low muscle mass. Considering only muscle mass muscle biopsy would have been successful in 18.7% of the frail older women and 21.4% of the frail older men. In this population, muscle biopsy was not feasible because of contra-indications in the majority of participants. This questions whether a biopsy sample obtained from frail older individuals, is actually representative of this population and supports the need to disclose biopsy failure rate in this population.}, } @article {pmid30477569, year = {2018}, author = {Lavrinienko, A and Tukalenko, E and Mappes, T and Watts, PC}, title = {Skin and gut microbiomes of a wild mammal respond to different environmental cues.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {209}, pmid = {30477569}, issn = {2049-2618}, support = {287153//Biotieteiden ja Ympäristön Tutkimuksen Toimikunta/ ; 268670//Biotieteiden ja Ympäristön Tutkimuksen Toimikunta/ ; }, abstract = {BACKGROUND: Animal skin and gut microbiomes are important components of host fitness. However, the processes that shape the microbiomes of wildlife are poorly understood, particularly with regard to exposure to environmental contaminants. We used 16S rRNA amplicon sequencing to quantify how exposure to radionuclides impacts the skin and gut microbiota of a small mammal, the bank vole Myodes glareolus, inhabiting areas within and outside the Chernobyl Exclusion Zone (CEZ), Ukraine.

RESULTS: Skin microbiomes of male bank voles were more diverse than females. However, the most pronounced differences in skin microbiomes occurred at a larger spatial scale, with higher alpha diversity in the skin microbiomes of bank voles from areas within the CEZ, whether contaminated by radionuclides or not, than in the skin microbiomes of animals from uncontaminated locations outside the CEZ, near Kyiv. Similarly, irrespective of the level of radionuclide contamination, skin microbiome communities (beta diversity) showed greater similarities within the CEZ, than to the areas near Kyiv. Hence, bank vole skin microbiome communities are structured more by geography than the level of soil radionuclides. This pattern presents a contrast with bank vole gut microbiota, where microbiomes could be strikingly similar among distant (~ 80 km of separation), uncontaminated locations, and where differences in microbiome community structure were associated with the level of radioactivity. We also found that the level of (dis)similarity between the skin and gut microbiome communities from the same individuals was contingent on the potential for exposure to radionuclides.

CONCLUSIONS: Bank vole skin and gut microbiomes have distinct responses to similar environmental cues and thus are structured at different spatial scales. Our study shows how exposure to environmental pollution can affect the relationship between a mammalian host's skin and gut microbial communities, potentially homogenising the microbiomes in habitats affected by pollution.}, } @article {pmid30477564, year = {2018}, author = {Getahun, DS and Wolde, HF and Muchie, KF and Yeshita, HY}, title = {Utilization and determinants of long term and permanent contraceptive methods among married reproductive age women at Janamora district, northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {836}, pmid = {30477564}, issn = {1756-0500}, abstract = {OBJECTIVE: This study is aimed at determining the prevalence and factors associated with utilization of long acting and permanent methods among married reproductive age (15-49) females at Janamora district, in 2018.

RESULT: Prevalence of long acting and permanent contraceptive method utilization was 12.9% (95% confidence interval (CI) 10%, 15%).Of those utilizers, 96.8% use implants, 2.1% use female sterilization and 1.1% use Intrauterine Contraceptive Device. Women's occupation, student as compared to housewife (Adjusted odds ratio (AOR) = 3.12, 95% CI 1.05-9.29), a women whose husband was government employed as compared to merchant (AOR = 2.51, 95% CI 1.1-5.75), and women who had high knowledge as compared to poor knowledge (AOR = 4.20, 95% CI 1.32-13.39) were positively associated with utilization of long acting and permanent contraceptive method.}, } @article {pmid30477563, year = {2018}, author = {Sinha, R and Ahsan, H and Blaser, M and Caporaso, JG and Carmical, JR and Chan, AT and Fodor, A and Gail, MH and Harris, CC and Helzlsouer, K and Huttenhower, C and Knight, R and Kong, HH and Lai, GY and Hutchinson, DLS and Le Marchand, L and Li, H and Orlich, MJ and Shi, J and Truelove, A and Verma, M and Vogtmann, E and White, O and Willett, W and Zheng, W and Mahabir, S and Abnet, C}, title = {Next steps in studying the human microbiome and health in prospective studies, Bethesda, MD, May 16-17, 2017.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {210}, pmid = {30477563}, issn = {2049-2618}, abstract = {The National Cancer Institute (NCI) sponsored a 2-day workshop, "Next Steps in Studying the Human Microbiome and Health in Prospective Studies," in Bethesda, Maryland, May 16-17, 2017. The workshop brought together researchers in the field to discuss the challenges of conducting microbiome studies, including study design, collection and processing of samples, bioinformatics and statistical methods, publishing results, and ensuring reproducibility of published results. The presenters emphasized the great potential of microbiome research in understanding the etiology of cancer. This report summarizes the workshop and presents practical suggestions for conducting microbiome studies, from workshop presenters, moderators, and participants.}, } @article {pmid30477558, year = {2018}, author = {Shaka, MF and Senbeto, GA}, title = {Assessment of students' attitude and level of community involvement in community-based education at training sites in Gedeo zone, South Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {835}, pmid = {30477558}, issn = {1756-0500}, support = {CER/2017/03//Dilla University/ ; }, abstract = {OBJECTIVE: This study was aimed to assess the students' attitude towards community based education and the level of community involvement in community-based education.

RESULT: Among the 634 community members participated in this study, 64.4% were aware of the community-based education program and 86.5% of these participants have favorable attitude towards the program. The level of community involvement in the activities of students in this study is 40.9%. About 72% of the students have favorable attitude towards community based education. Female students were more likely to have favorable attitude toward the program [AOR: 7.64 (CI 1.80, 32.50)]. On the other hand, students who have low participation during group assignment [AOR: 0.07 (CI 0.01, 0.95)] and those with lower socially conscious attitude [AOR: 0.02 (0.01, 0.08)] were less likely to have favorable attitude.}, } @article {pmid30477553, year = {2018}, author = {Chali, SW and Salih, MH and Abate, AT}, title = {Self-care practice and associated factors among Diabetes Mellitus patients on follow up in Benishangul Gumuz Regional State Public Hospitals, Western Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {833}, pmid = {30477553}, issn = {1756-0500}, abstract = {OBJECTIVE: The aim of this study was to assess the self-care practice among patients with diabetes and their associated factors in Benishangul Gumuz Public Hospitals, Western Ethiopia, 2018.

RESULT: Out of the total 399 selected patients, 383 were participated in the study with a response rate of 96%. From 383 respondents, 45.7% had poor diabetes self-care practice. Unable to read and write (AOR = 3.63, 95% CI 1.33-9.89, p = 0.011), never had a diabetic health education (AOR = 4.09, 95% CI 1.89, 8.84, p = 0.000), not having glucometer (AOR = 2.66, 95% CI 1.30, 5.46 p = 0.007), poor diabetic knowledge (AOR = 5.01, 95% CI 2.44, 10.28, p = 0.000), poor self-efficacy (AOR = 3.00, 95% CI 1.76, 5.11, p = 0.000) and not having social support (AOR = 1.84, 95% CI 1.08, 3.13, p = 0.023) were significantly associated with poor self-care practice of diabetes patients. These findings request for the need of integrated interventional management approach, which will improve the health and quality of life of the diabetes patients.}, } @article {pmid30477540, year = {2018}, author = {Guesh, G and Degu, G and Abay, M and Beyene, B and Brhane, E and Brhane, K}, title = {Survival status and predictors of mortality among children with severe acute malnutrition admitted to general hospitals of Tigray, North Ethiopia: a retrospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {832}, pmid = {30477540}, issn = {1756-0500}, abstract = {OBJECTIVE: Despite the presence standard protocol for management of severe acute malnutrition case-fatality rates in African hospitals remain unacceptably high. The case in Ethiopia is not different from others. Therefore, this study was aimed to assess survival status and predictors of mortality among children with severe acute malnutrition admitted to stabilization centers of general hospitals in Tigray region, northern Ethiopia. A 24 months retrospective longitudinal study was conducted among 569 randomly selected medical records of children admitted to stabilizing centers. Both bi-variable and multivariable Cox regression analysis was conducted to identify predictors of mortality. Association was summarized using AHR, and statistical significances were declared at 95% CI and P-value < 0.05.

RESULTS: During follow up, 456 [82%] of children had got cured, 37 [6.65%] were absconded and 21 [3.8%] were died. The overall mean survival time was 41.93 [95% CI 40.17-43.68] days. Impaired conscious level [AHR = 6.69, 95% CI 2.43-19.93], development of comorbidity after admission [AHR 12.71, 95% CI 2.79-57.94] and being urban in residence [AHR = 2.73, 95% CI 1.12-6.64] were predictors of mortality. Therefore, interventions to reduce further mortality should focus in children having impaired consciousness level and who developed comorbidity after admission.}, } @article {pmid30477489, year = {2018}, author = {Jacobson, EC and Perry, JK and Long, DS and Olins, AL and Olins, DE and Wright, BE and Vickers, MH and O'Sullivan, JM}, title = {Migration through a small pore disrupts inactive chromatin organization in neutrophil-like cells.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {142}, pmid = {30477489}, issn = {1741-7007}, abstract = {BACKGROUND: Mammalian cells are flexible and can rapidly change shape when they contract, adhere, or migrate. The nucleus must be stiff enough to withstand cytoskeletal forces, but flexible enough to remodel as the cell changes shape. This is particularly important for cells migrating through confined spaces, where the nuclear shape must change in order to fit through a constriction. This occurs many times in the life cycle of a neutrophil, which must protect its chromatin from damage and disruption associated with migration. Here we characterized the effects of constricted migration in neutrophil-like cells.

RESULTS: Total RNA sequencing identified that migration of neutrophil-like cells through 5- or 14-μm pores was associated with changes in the transcript levels of inflammation and chemotaxis-related genes when compared to unmigrated cells. Differentially expressed transcripts specific to migration with constriction were enriched for groups of genes associated with cytoskeletal remodeling. Hi-C was used to capture the genome organization in control and migrated cells. Limited switching was observed between the active (A) and inactive (B) compartments after migration. However, global depletion of short-range contacts was observed following migration with constriction compared to migration without constriction. Regions with disrupted contacts, TADs, and compartments were enriched for inactive chromatin.

CONCLUSION: Short-range genome organization is preferentially altered in inactive chromatin, possibly protecting transcriptionally active contacts from the disruptive effects of migration with constriction. This is consistent with current hypotheses implicating heterochromatin as the mechanoresponsive form of chromatin. Further investigation concerning the contribution of heterochromatin to stiffness, flexibility, and protection of nuclear function will be important for understanding cell migration in relation to human health and disease.}, } @article {pmid30477446, year = {2018}, author = {Zhao, Q and Mao, Q and Zhao, Z and Dou, T and Wang, Z and Cui, X and Liu, Y and Fan, X}, title = {Prediction of plant-derived xenomiRs from plant miRNA sequences using random forest and one-dimensional convolutional neural network models.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {839}, pmid = {30477446}, issn = {1471-2164}, support = {02120022118016//The Fundamental Research Funds for the Central Universities/ ; 2018JBC14L19//Training Project for Youth Scholars of Changchun University/ ; 61501101//National Natural Science Foundation of China/ ; 31801623//Young Scientists Fund/ ; }, abstract = {BACKGROUND: An increasing number of studies reported that exogenous miRNAs (xenomiRs) can be detected in animal bodies, however, some others reported negative results. Some attributed this divergence to the selective absorption of plant-derived xenomiRs by animals.

RESULTS: Here, we analyzed 166 plant-derived xenomiRs reported in our previous study and 942 non-xenomiRs extracted from miRNA expression profiles of four species of commonly consumed plants. Employing statistics analysis and cluster analysis, our study revealed the potential sequence specificity of plant-derived xenomiRs. Furthermore, a random forest model and a one-dimensional convolutional neural network model were trained using miRNA sequence features and raw miRNA sequences respectively and then employed to predict unlabeled plant miRNAs in miRBase. A total of 241 possible plant-derived xenomiRs were predicted by both models. Finally, the potential functions of these possible plant-derived xenomiRs along with our previously reported ones in human body were analyzed.

CONCLUSIONS: Our study, for the first time, presents the systematic plant-derived xenomiR sequences analysis and provides evidence for selective absorption of plant miRNA by human body, which could facilitate the future investigation about the mechanisms underlying the transference of plant-derived xenomiR.}, } @article {pmid30477445, year = {2018}, author = {Jiang, J and Gai, Z and Wang, Y and Fan, K and Sun, L and Wang, H and Ding, Z}, title = {Comprehensive proteome analyses of lysine acetylation in tea leaves by sensing nitrogen nutrition.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {840}, pmid = {30477445}, issn = {1471-2164}, support = {SDAIT-19-01//The technology system of modern agricultural industry in Shandong Province/ ; }, abstract = {BACKGROUND: Nε-Acetylation of lysine residues, a frequently occurring post-translational modification, plays important functions in regulating physiology and metabolism. However, the information of global overview of protein acetylome under nitrogen-starvation/resupply in tea (Camellia sinensis) leaves was limited. And the full function of lysine acetylated proteins of tea plants in nitrogen absorption and assimilation remains unclear.

RESULTS: Here, we performed the global review of lysine acetylome in tea leaves under nitrogen (N)-starvation/resupply, using peptide prefractionation, immunoaffinity enrichment, and coupling with high sensitive LC-MS/MS combined with affinity purification analysis. Altogether, 2229 lysine acetylation sites on 1286 proteins were identified, of which 16 conserved motifs in E*KacK, Kac*K, Kac*R, Kac*HK, Kac*N, Kac*S, Kac*T, Kac*D, were extracted from 2180 acetylated peptides. Approximately, 36.76% of the acetylated lysines were located in the regions of ordered secondary structures. The most of the identified lysine acetylation proteins were located in the chloroplast (39%) and cytoplasm (29%). The largest group of acetylated proteins consisted of many enzymes, such as ATP synthase, ribosomal proteins and malate dehydrogenase [NADP], which were related to metabolism (38%) in the biological process. These acetylated proteins were mainly enriched in three primary protein complexes of photosynthesis: photosystem I, photosystem II and the cytochrome b6/f complex. And some acetylated proteins related to glycolysis and secondary metabolite biosynthesis were increased/decreased under N-resupply. Moreover, the PPI (protein-protein interaction) analysis revealed that the diverse interactions of identified acetylated proteins mainly involved in photosynthesis and ribosome.

CONCLUSION: The results suggested that lysine acetylated proteins might play regulating roles in metabolic process in tea leaves. The critical regulatory roles mainly involved in diverse aspects of metabolic processes, especially in photosynthesis, glycolysis and secondary metabolism. A lot of proteins related to the photosynthesis and glycolysis were found to be acetylated, including LHCA1, LHCA3, LHCB6, psaE, psaD, psaN, GAPDH, PEPC, ENL and petC. And some proteins related to flavonoids were also found to be acetylated, including PAL, DFR, naringenin 3-dioxygenase and CHI. The provided data may serve as important resources for exploring the physiological, biochemical, and genetic role of lysine acetylation in tea plants. Data are available via ProteomeXchange with identifier PXD008931.}, } @article {pmid30477444, year = {2018}, author = {Fernández Rodríguez, A and de Santiago Rodrigo, L and López Guillén, E and Rodríguez Ascariz, JM and Miguel Jiménez, JM and Boquete, L}, title = {Coding Prony's method in MATLAB and applying it to biomedical signal filtering.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {451}, pmid = {30477444}, issn = {1471-2105}, mesh = {Adult ; *Algorithms ; *Evoked Potentials, Visual ; Female ; Fourier Analysis ; Humans ; Least-Squares Analysis ; Male ; Multiple Sclerosis/diagnosis ; Programming Languages ; Young Adult ; }, abstract = {BACKGROUND: The response of many biomedical systems can be modelled using a linear combination of damped exponential functions. The approximation parameters, based on equally spaced samples, can be obtained using Prony's method and its variants (e.g. the matrix pencil method). This paper provides a tutorial on the main polynomial Prony and matrix pencil methods and their implementation in MATLAB and analyses how they perform with synthetic and multifocal visual-evoked potential (mfVEP) signals. This paper briefly describes the theoretical basis of four polynomial Prony approximation methods: classic, least squares (LS), total least squares (TLS) and matrix pencil method (MPM). In each of these cases, implementation uses general MATLAB functions. The features of the various options are tested by approximating a set of synthetic mathematical functions and evaluating filtering performance in the Prony domain when applied to mfVEP signals to improve diagnosis of patients with multiple sclerosis (MS).

RESULTS: The code implemented does not achieve 100%-correct signal approximation and, of the methods tested, LS and MPM perform best. When filtering mfVEP records in the Prony domain, the value of the area under the receiver-operating-characteristic (ROC) curve is 0.7055 compared with 0.6538 obtained with the usual filtering method used for this type of signal (discrete Fourier transform low-pass filter with a cut-off frequency of 35 Hz).

CONCLUSIONS: This paper reviews Prony's method in relation to signal filtering and approximation, provides the MATLAB code needed to implement the classic, LS, TLS and MPM methods, and tests their performance in biomedical signal filtering and function approximation. It emphasizes the importance of improving the computational methods used to implement the various methods described above.}, } @article {pmid30477439, year = {2018}, author = {Vrbanac, A and Riestra, AM and Coady, A and Knight, R and Nizet, V and Patras, KA}, title = {The murine vaginal microbiota and its perturbation by the human pathogen group B Streptococcus.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {197}, pmid = {30477439}, issn = {1471-2180}, support = {HL107150//National Heart, Lung, and Blood Institute/ ; Seed Grant//UCSD Center for Microbiome Innovation/ ; GM06852//National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: Composition of the vaginal microbiota has significant influence on female urogenital health and control of infectious disease. Murine models are widely utilized to characterize host-pathogen interactions within the vaginal tract, however, the composition of endogenous vaginal flora remains largely undefined with modern microbiome analyses. Here, we employ 16S rRNA amplicon sequencing to establish the native microbial composition of the vaginal tract in adult C57Bl/6 J mice. We further interrogate the impact of estrous cycle and introduction of the human vaginal pathobiont, group B Streptococcus (GBS) on community state type and stability, and conversely, the impact of the vaginal microbiota on GBS persistence.

RESULTS: Sequencing analysis revealed five distinctive community states of the vaginal microbiota dominated largely by Staphylococcus and/or Enterococcus, Lactobacillus, or a mixed population. Stage of estrus did not impact microbial composition. Introduction of GBS decreased community stability at early timepoints; and in some mice, GBS became the dominant bacterium by day 21. Endogenous Staphylococcus abundance correlated with GBS ascension into the uterus, and increased community stability in GBS-challenged mice.

CONCLUSIONS: The murine vaginal flora is diverse and fluctuates independently of the estrous cycle. Endogenous flora may impact pathogen colonization and dissemination and should be considered in urogenital infection models.}, } @article {pmid30477435, year = {2018}, author = {Nadal, J and Ponz, C and Margalida, A}, title = {Body proportions for the facilitation of walking, running and flying: the case of partridges.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {176}, pmid = {30477435}, issn = {1471-2148}, mesh = {Animals ; Birds/*anatomy & histology/*physiology ; *Body Size ; Female ; Flight, Animal/*physiology ; Male ; Models, Biological ; Running/*physiology ; Walking/*physiology ; }, abstract = {BACKGROUND: Predation is one of the most important natural selection forces. Prey species can optimize feeding behavior and escape from predators based on mobility conditioned by body proportions. With age, mobility capacity increases and individuals are more efficient in finding resources and safety (e.g., food and refuge). Birds' mobility is driven by the dimensions, of the head and torso, as well as the extremities and flight feathers. To assess the relationship between body traits and to understand how body proportions are organized in wild Red-legged partridges (Alectoris rufa), we used biometric data from nearly 14,000 individuals, obtained during a long-term study (1988-2011) on a wild population.

RESULTS: We used GLMs and regressions to model the relationship between body mass and the size of body parts. We found that wing length was the morphological part best explained by other body trait measures. Wing length models were better predictors in juveniles than in adults and in females than in males. Wing length and feather length, mass and total length are the most strongly related parts; mass and wing length, total length and feather length are moderately related. The association between mass and wing length is intermediated by feather length and total length.

CONCLUSIONS: Social inclusion, feeding and predator evasion may be affected by body structure intermediated by mobility and health. Our results suggest that proportions of the body, extremities and flight feathers drive mobility which is intimately associated with ecology, biological efficiency, health and physical optimization. Our findings showed that wing size was strongly allied to other body part measurements, enhancing the importance of body structure conformation for flight. Our study highlights the scaled relationship of body structure among age-sex classes and its relevance to social cohesion, flock movement and the balance between predation and starvation.}, } @article {pmid30477433, year = {2018}, author = {Guilhamon, P and Lupien, M}, title = {SMuRF: a novel tool to identify regulatory elements enriched for somatic point mutations.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {454}, pmid = {30477433}, issn = {1471-2105}, support = {SU2C-AACR-DT-19-15//Stand Up To Cancer (CDN)/ ; RS2014-04//Prostate Cancer Canada/ ; MFE 338954//Institute of Cancer Research/ ; }, mesh = {Genomics ; Humans ; Liver Neoplasms/genetics ; *Point Mutation ; *Regulatory Sequences, Nucleic Acid ; *Software ; }, abstract = {BACKGROUND: Single Nucleotide Variants (SNVs), including somatic point mutations and Single Nucleotide Polymorphisms (SNPs), in noncoding cis-regulatory elements (CREs) can affect gene regulation and lead to disease development. Several approaches have been developed to identify highly mutated regions, but these do not take into account the specific genomic context, and thus likelihood of mutation, of CREs.

RESULTS: Here, we present SMuRF (Significantly Mutated Region Finder), a user-friendly command-line tool to identify these significantly mutated regions from user-defined genomic intervals and SNVs. We demonstrate this using publicly available datasets in which SMuRF identifies 72 significantly mutated CREs in liver cancer, including known mutated gene promoters as well as previously unreported regions.

CONCLUSIONS: SMuRF is a helpful tool to allow the simple identification of significantly mutated regulatory elements. It is open-source and freely available on GitHub (https://github.com/LupienLab/SMURF).}, } @article {pmid30477429, year = {2018}, author = {Zienkiewicz, K and Benning, U and Siegler, H and Feussner, I}, title = {The type 2 acyl-CoA:diacylglycerol acyltransferase family of the oleaginous microalga Lobosphaera incisa.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {298}, pmid = {30477429}, issn = {1471-2229}, support = {266401//European Commission FP7/ ; }, mesh = {Acyl Coenzyme A/genetics/*metabolism ; Chlorophyta/*enzymology/genetics ; Diacylglycerol O-Acyltransferase/genetics/*metabolism ; Fatty Acids/metabolism ; Genome, Plant ; Lipid Metabolism ; Microalgae/*enzymology/genetics ; Nitrogen/metabolism ; Transformation, Genetic ; Yeasts/genetics ; }, abstract = {BACKGROUND: Oleaginous microalgae are promising sources of energy-rich triacylglycerols (TAGs) for direct use for food, feed and industrial applications. Lobosphaera incisa is a fresh water unicellular alga, which in response to nutrient stress accumulates a high amount of TAGs with a high proportion of arachidonic acid (ARA). The final committed step of de novo TAG biosynthesis is catalyzed by acyl-CoA:diacylglycerol acyltransferases (DGATs), which add a fatty acid (FA) to the final sn-3 position of diacylglycerol (DAG).

RESULTS: Genome analysis revealed the presence of five putative DGAT isoforms in L. incisa, including one DGAT of type 1, three DGATs of type 2 and a single isoform of a type 3 DGAT. For LiDGAT1, LiDGAT2.1, LiDGAT2.2 and LiDGAT2.3 enzyme activity was confirmed by expressing them in the TAG-deficient yeast strain H1246. Feeding experiments of yeast transformants with fatty acids suggest a broad substrate specificity spectrum for LiDGAT1. A significant TAG production in response to exogenous ARA was found for LiDGAT2.2. Cellular localization of the four type 1 and type 2 DGATs expressed in yeast revealed that they all localize to distinct ER domains. A prominent association of LiDGAT1 with ER domains in close proximity to forming lipid droplets (LDs) was also observed.

CONCLUSIONS: The data revealed a distinct molecular, functional and cellular nature of type 1 and type 2 DGATs from L. incisa, with LiDGAT1 being a major contributor to the TAG pool. LiDGATs of type 2 might be in turn involved in the incorporation of unusual fatty acids into TAG and thus regulate the composition of TAG. This report provides a valuable resource for the further research of microalgae DGATs oriented towards production of fresh-water strains with higher oil content of valuable composition, not only for oil industry but also for human and animal nutrition.}, } @article {pmid30477428, year = {2018}, author = {Chao, Y and Yuan, J and Li, S and Jia, S and Han, L and Xu, L}, title = {Analysis of transcripts and splice isoforms in red clover (Trifolium pratense L.) by single-molecule long-read sequencing.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {300}, pmid = {30477428}, issn = {1471-2229}, support = {31601989//National Natural Science Foundation of China/ ; 31672477//National Natural Science Foundation of China/ ; }, mesh = {*Alternative Splicing ; Exons ; Genome, Plant ; Introns ; Molecular Sequence Annotation ; Protein Isoforms/genetics ; RNA, Long Noncoding ; *RNA, Plant ; Sequence Analysis, RNA ; Transcriptome ; Trifolium/*genetics ; }, abstract = {BACKGROUND: Red clover (Trifolium pratense L.) is an important cool-season legume plant, which is the most widely planted forage legume after alfalfa. Although a draft genome sequence was published already, the sequences and completed structure of mRNA transcripts remain unclear, which limit further explore on red clover.

RESULTS: In this study, the red clover transcriptome was sequenced using single-molecule long-read sequencing to identify full-length splice isoforms, and 29,730 novel isoforms from known genes and 2194 novel isoforms from novel genes were identified. A total of 5492 alternative splicing events was identified and the majority of alter spliced events in red clover was corrected as intron retention. In addition, of the 15,229 genes detected by SMRT, 8719 including 186,517 transcripts have at least one poly(A) site. Furthermore, we identified 4333 long non-coding RNAs and 3762 fusion transcripts.

CONCLUSIONS: We analyzed full-length transcriptome of red clover with PacBio SMRT. Those new findings provided important information for improving red clover draft genome annotation and fully characterization of red clover transcriptome.}, } @article {pmid30477427, year = {2018}, author = {A Talip, B and Snelling, WJ and Sleator, RD and Lowery, C and Dooley, JSG}, title = {A rapid and sensitive system for recovery of nucleic acids from Mycobacteria sp. on archived glass slides.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {196}, pmid = {30477427}, issn = {1471-2180}, support = {SLAB-KPT scholarship//Ministry of Higher Education Malaysia and Universiti Tun Hussein Onn Malaysia (MY)/ ; }, abstract = {BACKGROUND: The field of diagnostics continues to advance rapidly with a variety of novel approaches, mainly dependent upon high technology platforms. Nonetheless much diagnosis, particularly in developing countries, still relies upon traditional methods such as microscopy. Biological material, particularly nucleic acids, on archived glass slides is a potential source of useful information both for diagnostic and epidemiological purposes. There are significant challenges faced when examining archived samples in order that an adequate amount of amplifiable DNA can be obtained. Herein, we describe a model system to detect low numbers of bacterial cells isolated from glass slides using (laser capture microscopy) LCM coupled with PCR amplification of a suitable target.

RESULTS: Mycobacterium smegmatis was used as a model organism to provide a proof of principle for a method to recover bacteria from a stained sample on a glass slide using a laser capture system. Ziehl-Neelsen (ZN) stained cells were excised and catapulted into tubes. Recovered cells were subjected to DNA extraction and pre-amplified with multiple displacement amplification (MDA). This system allowed a minimum of 30 catapulted cells to be detected following a nested real-time PCR assay, using rpoB specific primers. The combination of MDA and nested real-time PCR resulted in a 30-fold increase in sensitivity for the detection of low numbers of cells isolated using LCM.

CONCLUSIONS: This study highlights the potential of LCM coupled with MDA as a tool to improve the recovery of amplifiable nucleic acids from archived glass slides. The inclusion of the MDA step was essential to enable downstream amplification. This platform should be broadly applicable to a variety of diagnostic applications and we have used it as a proof of principle with a Mycobacterium sp. model system.}, } @article {pmid30477426, year = {2018}, author = {Yang, Q and Yang, Z and Tang, H and Yu, Y and Chen, Z and Wei, S and Sun, Q and Peng, Z}, title = {High-density genetic map construction and mapping of the homologous transformation sterility gene (hts) in wheat using GBS markers.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {301}, pmid = {30477426}, issn = {1471-2229}, support = {31760425//National Natural Science Foundation of China/ ; 16JC022//Foundation of Science & Technology department of Sichuan Province/ ; 17C043//National General Cultivation Project of China West Normal University/ ; }, mesh = {*Chromosome Mapping/methods ; *Chromosomes, Plant ; Fertility/genetics ; Flowers/genetics ; *Genes, Plant ; Genetic Markers ; Genotype ; Mutation ; Triticum/*genetics ; }, abstract = {BACKGROUND: Homologous transformation sterility-1 (HTS-1) is a novel wheat mutant that exhibits pistillody, the transformation of stamens into pistils or pistil-like structures. More extreme phenotypes of this mutation can have six pistils or pistil-like structures without any stamens in a floret. Thus, HTS-1 is highly valuable for studies of wheat hybrid breeding and flower development. Previous studies have shown that two major genes (Pis1 and hts) control pistillody in HTS-1. The Pis1 gene controls the three-pistil trait in the three-pistil wheat mutant and has been mapped on chromosome 2D, but the hts gene has not been mapped or identified. To do so, we crossed HTS-1 with CM28TP (three-pistil mutant) and constructed a high-density linkage map with the F2 population (200 individuals).

RESULTS: The map covered 2779.96 cM, and the genetic distance per chromosome ranged from 37.59 cM to 318.95 cM. The average distance between markers was 1.04 cM. We then mapped hts between GBS-SNP markers 4A_109 and 4A_119, separated by 2.0 cM and 5.2 Mb. To find the candidate genes, the hts region was enlarged to 7.2 Mb, encompassing 752 protein-coding genes. We identified TaWin1 as a possible candidate gene after comparing the 752 genes with 206 common differentially expressed genes between pistillody stamens (PS) versus normal stamens (S) and pistils (P) versus S. Real-time PCR indicated that TaWin1 was highly expressed in HTS-1 during the pistil-and-stamen-differentiating stage, at levels approximately 120 times greater than those in CM28TP. Further analysis indicated that TaWin1 was mainly expressed in HTS-1 PS, supporting its status as a candidate gene of hts. Thus, TaWin1 overexpression probably leads to the transformation of stamens into pistils in wheat.

CONCLUSIONS: The results of this study provide a foundation for further research on stamen and pistil development, with implications for wheat-hybrid breeding programs.}, } @article {pmid30477425, year = {2018}, author = {Gan, Y and Song, Y and Chen, Y and Liu, H and Yang, D and Xu, Q and Zheng, Z}, title = {Transcriptome analysis reveals a composite molecular map linked to unique seed oil profile of Neocinnamomum caudatum (Nees) Merr.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {303}, pmid = {30477425}, issn = {1471-2229}, support = {31600526//National Natural Science Foundation of China/ ; 31370287//National Natural Science Foundation of China/ ; 31301547//National Natural Science Foundation of China/ ; LQ15C020002//Zhejiang Provincial Natural Science Foundation of China/ ; 2014FR007//Zhejiang A and F University/ ; }, mesh = {Fatty Acids/biosynthesis ; Gene Expression Profiling ; Genes, Plant ; Lauraceae/*genetics/metabolism ; Plant Oils/*metabolism ; Seeds/genetics/growth & development ; Triglycerides/biosynthesis ; }, abstract = {BACKGROUND: Neocinnamomum caudatum (Nees) Merr., a biodiesel tree species in the subtropical areas of South China, India and Burma, is distinctive from other species in Lauraceae family and its seed oil is rich in linoleic acid (18:2) and stearic acid (18:0). However, there is little genetic information about this species so far. In this study, a transcriptomic analysis on developing seeds of N. caudatum was conducted in an attempt to discern the molecular mechanisms involving the control of the fatty acid (FA) and triacylglycerol (TAG) biosynthesis.

RESULTS: Transcriptome analysis revealed 239,703 unigenes with an average length of 436 bp and 137 putative biomarkers that are related to FA formation and TAG biosynthesis. The expression patterns of genes encoding β-ketoacyl-acyl carrier protein synthase I (KASI), β- ketoacyl-acyl carrier protein synthase II (KASII), stearoyl-ACP desaturase (SAD), fatty acid desaturase 2 (FAD2), fatty acid desaturase 8 (FAD8) and acyl-ACP thioesterase A/B (FATA/B) were further validated by qRT-PCR. These genes displayed a very similar expression pattern in two distinct assays. Moreover, sequence analysis of different FATBs from diverse plant species revealed that NcFATB is structurally different from its counterpart in other species in producing medium-chain saturated FAs. Concertedly, heterologous expression of NcFATB in E. coli BL21 (DE3) strain showed that this corresponding expressed protein, NcFATB, prefers long-chain saturated fatty acyl-ACP over medium-chain fatty acyl-ACP as substrate.

CONCLUSIONS: Transcriptome analysis of developing N. caudatum seeds revealed a composite molecular map linked to the FA formation and oil biosynthesis in this biodiesel tree species. The substrate preference of NcFATB for long-chain saturated FAs is likely to contribute to its unique seed oil profile rich in stearic acid. Our findings demonstrate that in the tree species of Lauraceae family, the FATB enzymes producing long-chain FAs are structurally distinct from those producing medium-chain FAs, thereby suggesting that the FATB genes may serve as a biomarker for the classification of tree species of Lauraceae family.}, } @article {pmid30477424, year = {2018}, author = {Guo, L and Cui, H and Zhao, G and Liu, R and Li, Q and Zheng, M and Guo, Y and Wen, J}, title = {Intramuscular preadipocytes impede differentiation and promote lipid deposition of muscle satellite cells in chickens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {838}, pmid = {30477424}, issn = {1471-2164}, support = {31372305//National Natural Science Foundation of China/ ; ASTIP-IAS04, ASTIP-IAS-TS-18//Agricultural Science and Technology Innovation Program/ ; CARS-41//Earmarked Fund for Modern Agro-Industry Technology Research System/ ; }, abstract = {BACKGROUND: Skeletal muscle satellite cells (MSC) are crucial for postnatal growth and regeneration of skeletal muscle. An interaction exists between MSC and intramuscular preadipocytes (IMPA). This study is the first to investigate the effects of IMPA on MSC in chickens and unveil the molecular mechanisms by transcriptome analysis.

RESULTS: Primary MSC and IMPA were isolated from the pectoralis major muscle of 7-day-old chickens. After both cell types reached confluence, MSC were cultured alone or co-cultured with IMPA for 2 or 4 d. MSC treated for 2 d were subjected to RNA-seq. A total of 1653 known differentially expressed genes (DEG) were identified between co-cultured and mono-cultured MSC (|log2 FC| ≥ 1, FDR < 0.01). Based on Gene Ontology analysis, 48 DEG related to muscle development were screened, including the key genes MYOD1, MYOG, PAX7, and TMEM8C. The 44 DEG related to lipid deposition included the key genes CD36, FABP4, ACSBG2, CYP7A1 and PLIN2. Most of the DEG related to muscle development were downregulated in co-cultured MSC, and DEG related to lipid deposition were upregulated. Immunofluorescence of MHC supported IMPA impeding differentiation of MSC, and Oil Red O staining showed concurrent promotion of lipid deposition. Pathway analysis found that several key genes were enriched in JNK/MAPK and PPAR signaling, which may be the key pathways regulating differentiation and lipid deposition in MSC. Additionally, pathways related to cell junctions may also contribute to the effect of IMPA on MSC.

CONCLUSIONS: The present study showed that IMPA impeded differentiation of MSC while promoting their lipid deposition. Pathway analysis indicated that IMPA might inhibit differentiation via the JNK/MAPK pathway, and promote lipid deposition via the PPAR pathway. This study supplies insights into the effect of IMPA on MSC, providing new clues on exposing the molecular mechanisms underlying the interplay between skeletal muscle and intramuscular fat in chickens.}, } @article {pmid30477421, year = {2018}, author = {Zhang, S and Zhang, R and Song, G and Gao, J and Li, W and Han, X and Chen, M and Li, Y and Li, G}, title = {Targeted mutagenesis using the Agrobacterium tumefaciens-mediated CRISPR-Cas9 system in common wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {302}, pmid = {30477421}, issn = {1471-2229}, support = {2016YFD0100500//Ministry of Science and Technology of the People's Republic of China (CN)/ ; 2017GNC10113//Key R&D Programme of Shandong Province/ ; 31601301//the National Natural Science Foundation of China/ ; 31501312//the National Natural Science Foundation of China/ ; ZR2014CM006//the Natural Science Foundation of Shandong Province/ ; 2016YQN01//the Youth Foundation of Shandong Academy of Agricultural Science/ ; 2018ZX0800910B-002//National Science and Technology Major Project of Breeding New Varieties of Genetically Modified Organisms/ ; 31701428//he National Natural Science Foundation of China/ ; CXGC2016C09//the Agricultural Science and Technology Innovation Project of Shandong Academy of Agricultural Sciences/ ; }, mesh = {Agrobacterium tumefaciens/*genetics ; *CRISPR-Cas Systems ; *Gene Targeting ; Genes, Plant ; *Mutagenesis ; Triticum/*genetics ; }, abstract = {BACKGROUND: Recently, the CRISPR/Cas9 system has been widely used to precisely edit plant genomes. Due to the difficulty in Agrobacterium-mediated genetic transformation of wheat, the reported applications in CRISPR/Cas9 system were all based on the biolistic transformation.

RESULTS: In the present study, we efficiently applied targeted mutagenesis in common wheat (Triticum aestivum L.) protoplasts and transgenic T0 plants using the CRISPR/Cas9 system delivered via Agrobacterium tumefaciens. Seven target sites in three genes (Pinb, waxy and DA1) were selected to construct individual expression vectors. The activities of the sgRNAs were evaluated by transforming the constructed vectors into wheat protoplasts. Mutations in the targets were detected by Illumina sequencing. Genome editing, including insertions or deletions at the target sites, was found in the wheat protoplast cells. The highest mutation efficiency was 6.8% in the DA1 gene. The CRISPR/Cas9 binary vector targeting the DA1 gene was then transformed into common wheat plants by Agrobacterium tumefaciens-mediated transformation, resulting in efficient target gene editing in the T0 generation. Thirteen mutant lines were generated, and the mutation efficiency was 54.17%. Mutations were found in the A and B genomes of the transgenic plants but not in the D genome. In addition, off-target mutations were not detected in regions that were highly homologous to the sgRNA sequences.

CONCLUSIONS: Our results showed that our Agrobacterium-mediated CRISPR/Cas9 system can be used for targeted mutations and facilitated wheat genetic improvement.}, } @article {pmid30477420, year = {2018}, author = {Lv, A and Su, L and Liu, X and Xing, Q and Huang, B and An, Y and Zhou, P}, title = {Characterization of Dehydrin protein, CdDHN4-L and CdDHN4-S, and their differential protective roles against abiotic stress in vitro.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {299}, pmid = {30477420}, issn = {1471-2229}, support = {31572451//Chinese Natural Science Foundation General Projects/ ; 31872419//Chinese Natural Science Foundation General Projects/ ; 2017FY100600//National Key R&D Program of China/ ; }, mesh = {Arabidopsis/genetics/growth & development ; Cloning, Molecular ; Cynodon/genetics/*physiology ; Plant Proteins/genetics/*physiology ; Protein Binding ; Protein Structure, Secondary ; *Stress, Physiological ; Temperature ; }, abstract = {BACKGROUND: Dehydrins play positive roles in regulating plant abiotic stress responses. The objective of this study was to characterize two dehydrin genes, CdDHN4-L and CdDHN4-S, generated by alternative splicing of CdDHN4 in bermudagrass.

RESULTS: Overexpression of CdDHN4-L with φ-segment and CdDHN4-S lacking of φ-segment in Arabidopsis significantly increased tolerance against abiotic stresses. The growth phenotype of Arabidopsis exposed to NaCl at 100 mM was better in plants overexpressing CdDHN4-L than those overexpressing CdDHN4-S, as well as better in E.coli cells overexpressing CdDHN4-L than those overexpressing CdDHN4-S in 300 and 400 mM NaCl, and under extreme temperature conditions at - 20 °C and 50 °C. The CdDHN4-L had higher disordered characterization on structures than CdDHN4-S at temperatures from 10 to 90 °C. The recovery activities of lactic dehydrogenase (LDH) and alcohol dehydrogenase (ADH) in presence of CdDHN4-L and CdDHN4-S were higher than that of LDH and ADH alone under freeze-thaw damage and heat. Protein-binding and bimolecular fluorescence complementation showed that both proteins could bind to proteins with positive isoelectric point via electrostatic forces.

CONCLUSIONS: These results indicate that CdDHN4-L has higher protective ability against abiotic stresses due to its higher flexible unfolded structure and thermostability in comparison with CdDHN4-S. These provided direct evidence of the function of the φ-segment in dehydrins for protecting plants against abiotic stress and to show the electrostatic interaction between dehydrins and client proteins.}, } @article {pmid30477419, year = {2018}, author = {Chantzi, E and Jarvius, M and Niklasson, M and Segerman, A and Gustafsson, MG}, title = {COMBImage: a modular parallel processing framework for pairwise drug combination analysis that quantifies temporal changes in label-free video microscopy movies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {453}, pmid = {30477419}, issn = {1471-2105}, support = {2013.0280//Knut och Alice Wallenbergs Stiftelse/ ; 2017-04655//Vetenskapsrådet/ ; }, mesh = {Algorithms ; Antineoplastic Combined Chemotherapy Protocols/therapeutic use ; Brain Neoplasms/drug therapy ; Cell Survival/drug effects ; Drug Discovery ; *Drug Therapy, Combination ; Glioblastoma/drug therapy ; Humans ; *Image Processing, Computer-Assisted ; Microscopy, Video/*methods ; Motion Pictures ; }, abstract = {BACKGROUND: Large-scale pairwise drug combination analysis has lately gained momentum in drug discovery and development projects, mainly due to the employment of advanced experimental-computational pipelines. This is fortunate as drug combinations are often required for successful treatment of complex diseases. Furthermore, most new drugs cannot totally replace the current standard-of-care medication, but rather have to enter clinical use as add-on treatment. However, there is a clear deficiency of computational tools for label-free and temporal image-based drug combination analysis that go beyond the conventional but relatively uninformative end point measurements.

RESULTS: COMBImage is a fast, modular and instrument independent computational framework for in vitro pairwise drug combination analysis that quantifies temporal changes in label-free video microscopy movies. Jointly with automated analyses of temporal changes in cell morphology and confluence, it performs and displays conventional cell viability and synergy end point analyses. The image processing algorithms are parallelized using Google's MapReduce programming model and optimized with respect to method-specific tuning parameters. COMBImage is shown to process time-lapse microscopy movies from 384-well plates within minutes on a single quad core personal computer. This framework was employed in the context of an ongoing drug discovery and development project focused on glioblastoma multiforme; the most deadly form of brain cancer. Interesting add-on effects of two investigational cytotoxic compounds when combined with vorinostat were revealed on recently established clonal cultures of glioma-initiating cells from patient tumor samples. Therapeutic synergies, when normal astrocytes were used as a toxicity cell model, reinforced the pharmacological interest regarding their potential clinical use.

CONCLUSIONS: COMBImage enables, for the first time, fast and optimized pairwise drug combination analyses of temporal changes in label-free video microscopy movies. Providing this jointly with conventional cell viability based end point analyses, it could help accelerating and guiding any drug discovery and development project, without use of cell labeling and the need to employ a particular live cell imaging instrument.}, } @article {pmid30477418, year = {2018}, author = {Zhang, R and Zhao, R and Zhao, X and Wu, D and Zheng, W and Feng, X and Zhou, F}, title = {pyHIVE, a health-related image visualization and engineering system using Python.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {452}, pmid = {30477418}, issn = {1471-2105}, support = {XDB13040400//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 20180622002JC//Jilin Provincial Key Laboratory of Big Data Intelligent Computing/ ; JJKH20180145KJ//Education Department of Jilin Province/ ; startup//Jilin University/ ; BMCPP-2018-001//Bioknow MedAI Institute/ ; NA//High Performance Computing Center of Jilin University, China/ ; }, mesh = {Algorithms ; Endoscopy, Gastrointestinal ; Humans ; Image Processing, Computer-Assisted/*methods ; Principal Component Analysis ; Programming Languages ; }, abstract = {BACKGROUND: Imaging is one of the major biomedical technologies to investigate the status of a living object. But the biomedical image based data mining problem requires extensive knowledge across multiple disciplinaries, e.g. biology, mathematics and computer science, etc. RESULTS: pyHIVE (a Health-related Image Visualization and Engineering system using Python) was implemented as an image processing system, providing five widely used image feature engineering algorithms. A standard binary classification pipeline was also provided to help researchers build data models immediately after the data is collected. pyHIVE may calculate five widely-used image feature engineering algorithms efficiently using multiple computing cores, and also featured the modules of Principal Component Analysis (PCA) based preprocessing and normalization.

CONCLUSIONS: The demonstrative example shows that the image features generated by pyHIVE achieved very good classification performances based on the gastrointestinal endoscopic images. This system pyHIVE and the demonstrative example are freely available and maintained at http://www.healthinformaticslab.org/supp/resources.php .}, } @article {pmid30476739, year = {2018}, author = {Korolik, V}, title = {The role of chemotaxis during Campylobacter jejuni colonisation and pathogenesis.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {32-37}, doi = {10.1016/j.mib.2018.11.001}, pmid = {30476739}, issn = {1879-0364}, abstract = {Campylobacter jejuni is a ubiquitous gastrointestinal pathogen, transmitted to humans from birds and animals, where C. jejuni is part of normal intestinal flora. In C. jejuni, similar to other motile bacteria, chemotaxis pathway and the array of chemosensors sense and respond to external stimuli with unique precision and sensitivity and are considered to be critical for bacterial colonisation and pathogenicity. Disruption of any component of the signal transduction pathway consisting of receptor-CheA/CheW-CheY-flagella cascade, the signal adaptation system, and even a loss of a single chemosensory receptor, dramatically reduce the ability of C. jejuni to colonise various animal hosts and to cause disease.}, } @article {pmid30476552, year = {2019}, author = {Hupało, K and Teixeira, MAL and Rewicz, T and Sezgin, M and Iannilli, V and Karaman, GS and Grabowski, M and Costa, FO}, title = {Persistence of phylogeographic footprints helps to understand cryptic diversity detected in two marine amphipods widespread in the Mediterranean basin.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {53-66}, doi = {10.1016/j.ympev.2018.11.013}, pmid = {30476552}, issn = {1095-9513}, abstract = {Amphipods of the genus Gammarus are a vital component of macrozoobenthic communities in European inland and coastal, marine and brackish waters of the Mediterranean and the Black Sea. Exceptional levels of cryptic diversity have been revealed for several widespread freshwater Gammarus species in Europe. No comprehensive assessment has yet been made for brackishwater counterparts, such as Gammarus aequicauda and G. insensibilis, which are among the most widely dispersed members of the so-called "G. locusta group" in the Mediterranean and in the Black Sea. Here we probe the diversity of these morphospecies examining the partitioning of mtDNA and nDNA across multiple populations along their distribution range and discuss it within the regional paleogeographic framework. We gathered molecular data from a collection of 166 individuals of G. aequicauda and G. insensibilis from 47 locations along their distribution range in the Mediterranean including the Black Sea. They were amplified for both mitochondrial COI and 16S rRNA as well as the nuclear 28S rRNA. All five MOTU delimitation methods (ABGD, BIN, bPTP, GMYC single and multiple threshold models) applied revealed deep divergence between Black Sea and Mediterranean populations in both G. aequicauda and G. insensibilis. There were eight distinct MOTUs delimited for G. aequicauda (6-18% K2P) and 4 MOTUs for G. insensibilis (4-14% K2P). No sympatric MOTUs were detected throughout their distribution range. Multimarker time-calibrated phylogeny indicated that divergence of both G. aequicauda and G. insensibilis species complexes started already in the late Oligocene/early Miocene with the split between clades inhabiting eastern and western part of the Mediterranean occurring in both species at the similar time. Our results indicate a high cryptic diversity within Mediterranean brackishwater Gammarus, similar to that observed for freshwater counterparts. Moreover, the phylogenetic history combined with the current geographic distribution indicate that the evolution of both studied Gammarus morphogroups has been strongly connected with the geological events in the Mediterranean Basin and it reflect the turbulent history of the area.}, } @article {pmid30476483, year = {2019}, author = {Yang, R and Wang, J and Zhou, Z and Qi, S and Ruan, S and Lin, Z and Xin, Q and Lin, Y and Chen, X and Xie, J}, title = {Role of caveolin-1 in epidermal stem cells during burn wound healing in rats.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {271-279}, doi = {10.1016/j.ydbio.2018.11.015}, pmid = {30476483}, issn = {1095-564X}, abstract = {Local transplantation of stem cells has therapeutic effects on skin damage but cannot provide satisfactory wound healing. Studies on the mechanisms underlying the therapeutic effects of stem cells on skin wound healing will be needed. Hence, in the present study, we explored the role of Caveolin-1 in epidermal stem cells (EpiSCs) in the modulation of wound healing. We first isolated EpiSCs from mouse skin tissues and established stable EpiSCs with overexpression of Caveolin-1 using a lentiviral construct. We then evaluated the epidermal growth factor (EGF)-induced cell proliferation ability using cell counting Kit-8 (CCK-8) assay and assessed EpiSC pluripotency by examining Nanog mRNA levels in EpiSCs. Furthermore, we treated mice with skin burn injury using EpiSCs with overexpression of Caveolin-1. Histological examinations were conducted to evaluate re-epithelialization, wound scores, cell proliferation and capillary density in wounds. We found that overexpression of Caveolin-1 in EpiSCs promoted EGF-induced cell proliferation ability and increased wound closure in a mouse model of skin burn injury. Histological evaluation demonstrated that overexpression of Caveolin-1 in EpiSCs promoted re-epithelialization in wounds, enhanced cellularity, and increased vasculature, as well as increased wound scores. Taken together, our results suggested that Caveolin-1 expression in the EpiSCs play a critical role in the regulation of EpiSC proliferation ability and alteration of EpiSC proliferation ability may be an effective approach in promoting EpiSC-based therapy in skin wound healing.}, } @article {pmid30476449, year = {2018}, author = {Czech, B and Munafò, M and Ciabrelli, F and Eastwood, EL and Fabry, MH and Kneuss, E and Hannon, GJ}, title = {piRNA-Guided Genome Defense: From Biogenesis to Silencing.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {131-157}, doi = {10.1146/annurev-genet-120417-031441}, pmid = {30476449}, issn = {1545-2948}, abstract = {PIWI-interacting RNAs (piRNAs) and their associated PIWI clade Argonaute proteins constitute the core of the piRNA pathway. In gonadal cells, this conserved pathway is crucial for genome defense, and its main function is to silence transposable elements. This is achieved through posttranscriptional and transcriptional gene silencing. Precursors that give rise to piRNAs require specialized transcription and transport machineries because piRNA biogenesis is a cytoplasmic process. The ping-pong cycle, a posttranscriptional silencing mechanism, combines the cleavage-dependent silencing of transposon RNAs with piRNA production. PIWI proteins also function in the nucleus, where they scan for nascent target transcripts with sequence complementarity, instructing transcriptional silencing and deposition of repressive chromatin marks at transposon loci. Although studies have revealed numerous factors that participate in each branch of the piRNA pathway, the precise molecular roles of these factors often remain unclear. In this review, we summarize our current understanding of the mechanisms involved in piRNA biogenesis and function.}, } @article {pmid30476448, year = {2018}, author = {Bonini, NM}, title = {Allan Campbell (April 27, 1929-April 19, 2018).}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {vi-vii}, doi = {10.1146/annurev-ge-52-011118-100001}, pmid = {30476448}, issn = {1545-2948}, } @article {pmid30476447, year = {2018}, author = {Szabó, A and Mayor, R}, title = {Mechanisms of Neural Crest Migration.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {43-63}, doi = {10.1146/annurev-genet-120417-031559}, pmid = {30476447}, issn = {1545-2948}, abstract = {Neural crest cells are a transient embryonic cell population that migrate collectively to various locations throughout the embryo to contribute a number of cell types to several organs. After induction, the neural crest delaminates and undergoes an epithelial-to-mesenchymal transition before migrating through intricate yet characteristic paths. The neural crest exhibits a variety of migratory behaviors ranging from sheet-like mass migration in the cephalic regions to chain migration in the trunk. During their journey, neural crest cells rely on a range of signals both from their environment and within the migrating population for navigating through the embryo as a collective. Here we review these interactions and mechanisms, including chemotactic cues of neural crest cells' migration.}, } @article {pmid30476446, year = {2018}, author = {Prossliner, T and Skovbo Winther, K and Sørensen, MA and Gerdes, K}, title = {Ribosome Hibernation.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {321-348}, doi = {10.1146/annurev-genet-120215-035130}, pmid = {30476446}, issn = {1545-2948}, abstract = {Protein synthesis consumes a large fraction of available resources in the cell. When bacteria encounter unfavorable conditions and cease to grow, specialized mechanisms are in place to ensure the overall reduction of costly protein synthesis while maintaining a basal level of translation. A number of ribosome-associated factors are involved in this regulation; some confer an inactive, hibernating state of the ribosome in the form of 70S monomers (RaiA; this and the following are based on Escherichia coli nomenclature) or 100S dimers (RMF and HPF homologs), and others inhibit translation at different stages in the translation cycle (RsfS, YqjD and paralogs, SRA, and EttA). Stationary phase cells therefore exhibit a complex array of different ribosome subpopulations that adjusts the translational capacity of the cell to the encountered conditions and ensures efficient reactivation of translation when conditions improve. Here, we review the current state of research regarding stationary phase-specific translation factors, in particular ribosome hibernation factors and other forms of translational regulation in response to stress conditions.}, } @article {pmid30476445, year = {2018}, author = {Aragón, L}, title = {The Smc5/6 Complex: New and Old Functions of the Enigmatic Long-Distance Relative.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {89-107}, doi = {10.1146/annurev-genet-120417-031353}, pmid = {30476445}, issn = {1545-2948}, abstract = {Smc5 and Smc6, together with the kleisin Nse4, form the heart of the enigmatic and poorly understood Smc5/6 complex, which is frequently viewed as a cousin of cohesin and condensin with functions in DNA repair. As novel functions for cohesin and condensin complexes in the organization of long-range chromatin architecture have recently emerged, new unsuspected roles for Smc5/6 have also surfaced. Here, I aim to provide a comprehensive overview of our current knowledge of the Smc5/6 complex, including its long-established function in genome stability, its multiple roles in DNA repair, and its recently discovered connection to the transcription inhibition of hepatitis B virus genomes. In addition, I summarize new research that is beginning to tease out the molecular details of Smc5/6 structure and function, knowledge that will illuminate the nuclear activities of Smc5/6 in the stability and dynamics of eukaryotic genomes.}, } @article {pmid30476045, year = {2018}, author = {Gill, S and Catchpole, R and Forterre, P}, title = {Extracellular membrane vesicles (EVs) in the three domains of life and beyond.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuy042}, pmid = {30476045}, issn = {1574-6976}, abstract = {Cells from all three domains of life, Archaea, Bacteria and Eukarya, produce extracellular vesicles (EVs) which are sometimes associated to filamentous structures known as nanopods or nanotubes. The mechanisms of EV biogenesis in the three domains remain poorly understood, although studies in Bacteria and Eukarya indicate that the regulation of lipid composition plays a major role in initiating membrane curvature. EVs are increasingly recognized as important mediators of intercellular communication via transfer of a wide variety of molecular cargoes. They have been implicated in many aspects of cell physiology such as stress response, inter-cellular competition, lateral gene transfer (via RNA or DNA), pathogenicity, and detoxification. Their role in various human pathologies and aging has aroused much interest in recent years. EVs can be used as decoys against viral attack but virus infected cells also produce EVs that boost viral infection. Here, we review current knowledge on EVs in the three domains of life and their interactions with the viral world.}, } @article {pmid30476039, year = {2018}, author = {Jia, LY and Chen, L and Keller, L and Wang, J and Xiao, JH and Huang, DW}, title = {Doublesex Evolution Is Correlated with Social Complexity in Ants.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3230-3242}, doi = {10.1093/gbe/evy250}, pmid = {30476039}, issn = {1759-6653}, abstract = {The Dmrt (doublesex and mab-3-related transcription factor) genes are transcription factors crucial for sex determination and sexual differentiation. In some social insects, doublesex (dsx) exhibits widespread caste-specific expression across different tissues and developmental stages and has been suggested as a candidate gene for regulating division of labor in social insects. We therefore conducted a molecular evolution analysis of the Dmrt gene family in 20 ants. We found that the insect-specific oligomerization domain of DSX, oligomerization domain 2, was absent in all ants, except for the two phylogenetically basal ant species (Ponerinae), whose social structure and organization resemble the presumed ancestral condition in ants. Phylogenetic reconstruction and selection analysis revealed that dsx evolved faster than the other three members of the Dmrt family. We found evidence for positive selection for dsx in the ant subfamilies with more advanced social organization (Myrmicinae and Formicinae), but not in the Ponerinae. Furthermore, we detected expression of two Dmrt genes, dsx and DMRT11E, in adult ants, and found a clear male-biased expression pattern of dsx in most species for which data are available. Interestingly, we did not detect male-biased expression of dsx in the two ant species that possess a genetic caste determination system. These results possibly suggest an association between the evolution of dsx and social organization as well as reproductive division of labor in ants.}, } @article {pmid30475202, year = {2019}, author = {Li, J and Kudo, C and Tonouchi, A}, title = {Capsulimonas corticalis gen. nov., sp. nov., an aerobic capsulated bacterium, of a novel bacterial order, Capsulimonadales ord. nov., of the class Armatimonadia of the phylum Armatimonadetes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {220-226}, doi = {10.1099/ijsem.0.003135}, pmid = {30475202}, issn = {1466-5034}, abstract = {An aerobic bacterial strain designated AX-7T was isolated from the trunk surface of a Japanese beech (Fagus crenata). Cells of strain AX-7T were Gram-stain-negative, non-spore-forming, non-motile rods (1.0-1.2 µm in width and 1.2-3.0 µm in length) with peritrichous fimbriae. Cells were capsulated, and a number of them were surrounded by a thick slime layer. During growth, large aggregates formed, and the culture medium became viscous probably owing to exopolysaccharide release from the slime layer. The temperature range for growth was 10-37 °C, with an optimum at 30 °C. The pH range for growth was 5.0-7.0, with an optimum at pH 6.0. Strain AX-7T used various sugars, including polysaccharides, and yeast extract as growth substrates. Strain AX-7T contained menaquinones MK-9 and MK-10 as the respiratory quinones, and C16 : 1ω5c, C16 : 1ω11c, C16 : 0 and C14 : 0 as the major cellular fatty acids. Four unidentified phospholipids and 11 unidentified polar lipids constituted the polar lipids. The DNA G+C content was 61.0 mol%. The cell-wall peptidoglycan contained ll-diaminopimelic acid. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain AX-7T belonged to the class Armatimonadia, its closest relative being Armatimonas rosea YO-36T, with sequence similarity of 88.1%. Based on data from this polyphasic study, we propose that strain AX-7T represents a new genus of a novel species within the novel order Capsulimonadales ord. nov. of the class Armatimonadia, for which the name Capsulimonas corticalis gen. nov., sp. nov. is proposed. The type strain of C. corticalis is AX-7T (=DSM 105890T=NBRC 113044T).}, } @article {pmid30474920, year = {2019}, author = {Bell, T}, title = {Next-generation experiments linking community structure and ecosystem functioning.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {20-22}, doi = {10.1111/1758-2229.12711}, pmid = {30474920}, issn = {1758-2229}, } @article {pmid30474918, year = {2018}, author = {Li, J and Dittrich, M}, title = {Dynamic polyphosphate metabolism in cyanobacteria responding to phosphorus availability.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14488}, pmid = {30474918}, issn = {1462-2920}, support = {//Canada Foundation for Innovation/ ; //Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Despite the crucial role of polyphosphate (polyP) in aquatic environments, its metabolism in cyanobacteria responding to nutrients is poorly understood. We investigate polyP in three cyanobacteria species, specifically unicellular picocyanobacteria, under various nutritional conditions. Our experiments show that the accumulation of polyP in cyanobacteria is strongly dynamic, depending on phosphate levels and growth stages. 'Overplus' uptake of phosphorus (P) during the lag phase leads to the rapid accumulation of polyP, followed by lower polyP quotas during the exponential growth stage as a result of competing 'luxury' P uptake and polyP utilization to support rapid cell division. Cyanobacteria are capable of P deficiency responses that preferentially maintain polyP. However, preferential utilization of polyP occurs under severe P stress, suggesting the crucial role of polyP as P reserve to support cellular survival. Strong variability was observed among different species of cyanobacteria in their ability to accumulate polyP, and likely in the threshold P levels at which preferential polyP degradation occurs. This suggests that some cyanobacteria may be more adaptive to P-stressed or P-fluctuating conditions. Our results explain and provide important insights into the variability of polyP observed in aquatic environments where picocyanobacteria are the dominant primary producers.}, } @article {pmid30474915, year = {2018}, author = {Zhao, Y and Qin, F and Zhang, R and Giovannoni, SJ and Zhang, Z and Sun, J and Du, S and Rensing, C}, title = {Pelagiphages in the Podoviridae family integrate into host genomes.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14487}, pmid = {30474915}, issn = {1462-2920}, support = {41706173//National Natural Science Foundation of China/ ; }, abstract = {The Pelagibacterales order (SAR11) in Alphaproteobacteria dominates marine surface bacterioplankton communities, where it plays a key role in carbon and nutrient cycling. SAR11 phages, known as pelagiphages, are among the most abundant phages in the ocean. Four pelagiphages that infect Pelagibacter HTCC1062 have been reported. Here, we report 11 new pelagiphages in the Podoviridae family. Comparative genomics classified these pelagiphages into the HTVC019Pvirus genus, which includes the previously reported pelagiphages HTVC011P and HTVC019P. Phylogenomic analysis clustered HTVC019Pvirus pelagiphages into three subgroups. Integrases were identified in all but one HTVC019Pvirus genome. Site-specific integration of HTVC019Pvirus pelagiphages into host tRNA genes was verified experimentally, demonstrating the capacity of these pelagiphages to propagate by both lytic and lysogenic infection. Evidence of pelagiphage integration was also retrieved from the Global Ocean Survey database, showing that prophages are found in natural SAR11 populations. HTVC019Pvirus pelagiphages could impact SAR11 populations by a variety of mechanisms, including mortality, genetic transduction and prophage-induced viral immunity. HTVC019Pvirus pelagiphages are a rare example of cultured lysogenic phage that can be implicated in ecological processes on broad scales. These pelagiphages have the potential to become a useful model for investigating strategies of host infection and phage-dependent horizontal gene transfer.}, } @article {pmid30474913, year = {2019}, author = {Beck, SV and Räsänen, K and Ahi, EP and Kristjánsson, BK and Skúlason, S and Jónsson, ZO and Leblanc, CA}, title = {Gene expression in the phenotypically plastic Arctic charr (Salvelinus alpinus): A focus on growth and ossification at early stages of development.}, journal = {Evolution & development}, volume = {21}, number = {1}, pages = {16-30}, doi = {10.1111/ede.12275}, pmid = {30474913}, issn = {1525-142X}, abstract = {Gene expression during development shapes the phenotypes of individuals. Although embryonic gene expression can have lasting effects on developmental trajectories, few studies consider the role of maternal effects, such as egg size, on gene expression. Using qPCR, we characterize relative expression of 14 growth and/or skeletal promoting genes across embryonic development in Arctic charr (Salvelinus alpinus). We test to what extent their relative expression is correlated with egg size and size at early life-stages within the study population. We predict smaller individuals to have higher expression of growth and skeletal promoting genes, due to less maternal resources (i.e., yolk) and prioritization of energy toward ossification. We found expression levels to vary across developmental stages and only three genes (Mmp9, Star, and Sgk1) correlated with individual size at a given developmental stage. Contrary to our hypothesis, expression of Mmp9 and Star showed a non-linear relationship with size (at post fertilization and hatching, respectively), whilst Sgk1 was higher in larger embryos at hatching. Interestingly, these genes are also associated with craniofacial divergence of Arctic charr morphs. Our results indicate that early life-stage variation in gene expression, concomitant to maternal effects, can influence developmental plasticity and potentially the evolution of resource polymorphism in fishes.}, } @article {pmid30474900, year = {2018}, author = {Herczeg, G and Urszán, TJ and Orf, S and Nagy, G and Kotrschal, A and Kolm, N}, title = {Brain size predicts behavioural plasticity in guppies (Poecilia reticulata): an experiment.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13405}, pmid = {30474900}, issn = {1420-9101}, support = {2012-03624//Swedish Research Council/ ; 2016-03435//Swedish Research Council/ ; 102 2013.0072//Knut and Alice Wallenberg/ ; 105517//Hungarian Scientific Research Fund OTKA-K/ ; ELTE/12423/40//ÚNKP-17-4 New National Excellence Program of the Ministry of Human Capacities, Hungary/ ; }, abstract = {Understanding how animal personality (consistent between-individual behavioural differences) arises has become a central topic in behavioural sciences. This endeavour is complicated by the fact that not only the mean behaviour of individuals (behavioural type) but also the strength of their reaction to environmental change (behavioural plasticity) varies consistently. Personality and cognitive abilities are linked, and we suggest that behavioural plasticity could also be explained by differences in brain size (a proxy for cognitive abilities), since accurate decisions are likely essential to make behavioural plasticity beneficial. We test this idea in guppies (Poecilia reticulata), artificially selected for large and small brain size, which show clear cognitive differences between selection lines. To test whether those lines differed in behavioural plasticity, we reared them in groups in structurally enriched environments and then placed adults individually into empty tanks, where we presented them daily with visual predator cues and monitored their behaviour for 20 days with video-aided motion tracking. We found that individuals differed consistently in activity and risk-taking, as well as in behavioural plasticity. In activity, only the large-brained lines demonstrated habituation (increased activity) to the new environment, whereas in risk-taking, we found sensitization (decreased risk-taking) in both brain size lines. We conclude that brain size, potentially via increasing cognitive abilities, may increase behavioural plasticity, which in turn can improve habituation to novel environments. However, the effects seem to be behaviour-specific. Our results suggest that brain size likely explains some of the variation in behavioural plasticity found at the intraspecific level.}, } @article {pmid30474707, year = {2018}, author = {Du, X and Cao, K and Tan, M and Pan, Q}, title = {Lactobacillus futsaii subsp. chongqingii subsp. nov., Isolated from a Traditional Chinese Pickle.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1601-2}, pmid = {30474707}, issn = {1432-0991}, support = {31170007//the National Natural Science Foundation of China/ ; }, abstract = {Strain CQ16Z1T was isolated from jamiecosley, a traditional Chinese pickle. The isolate was Gram-positive, non-motile, non-spore-forming, facultatively anaerobic, catalase-negative, and long rod-shaped. The optimal temperature for growth was 37 °C and the DNA G + C content was 39.1 mol%. The results of 16S rRNA and rpoA gene sequencing, DNA-DNA hybridization, and peptidoglycan type analyses indicated that strain CQ16Z1T belongs to the recognized species Lactobacillus futsaii. However, the analysis results of pheS gene sequencing, amplified fragment length polymorphism, phenotypic profiles, cellular fatty acid, cell-wall monosaccharide determination, and cell morphology revealed that the novel strain was obviously different from the type strain L. futsaii JCM17355T, and had genetic relationship with Weissella cibaria to a certain degree, suggesting that the novel strain represents a novel subspecies of L. futsaii, for which the following names are proposed: L. futsaii subsp. futsaii subsp. nov. (type strain YM0097T = JCM 17355T = BCRC 80278T) and L. futsaii subsp. chongqingii subsp.nov., with the type strain CQ16Z1T (= CCTCC AB2017187T = KCTC 21089T).}, } @article {pmid30473011, year = {2018}, author = {Hutson, KS and Cable, J and Grutter, AS and Paziewska-Harris, A and Barber, I}, title = {Aquatic Parasite Cultures and Their Applications.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1082-1096}, doi = {10.1016/j.pt.2018.09.007}, pmid = {30473011}, issn = {1471-5007}, abstract = {In this era of unprecedented growth in aquaculture and trade, aquatic parasite cultures are essential to better understand emerging diseases and their implications for human and animal health. Yet culturing parasites presents multiple challenges, arising from their complex, often multihost life cycles, multiple developmental stages, variable generation times and reproductive modes. Furthermore, the essential environmental requirements of most parasites remain enigmatic. Despite these inherent difficulties, in vivo and in vitro cultures are being developed for a small but growing number of aquatic pathogens. Expanding this resource will facilitate diagnostic capabilities and treatment trials, thus supporting the growth of sustainable aquatic commodities and communities.}, } @article {pmid30472994, year = {2018}, author = {Gelvin, SB}, title = {The VirE-asy Way to Genetically Transform Plants.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {973-975}, doi = {10.1016/j.tim.2018.10.003}, pmid = {30472994}, issn = {1878-4380}, abstract = {Agrobacterium transfers T-DNA and several virulence effector proteins to plant cells. It is not known how and where T-complexes containing these components are assembled. A new study suggests that T-complexes form on the plant plasma membrane, mediated by the effector protein VirE3.}, } @article {pmid30472993, year = {2018}, author = {Zhang, X and Luo, T and Shen, Y}, title = {Deciphering the Sharp Decrease in H7N9 Human Infections.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {971-973}, doi = {10.1016/j.tim.2018.10.002}, pmid = {30472993}, issn = {1878-4380}, abstract = {The H7N9 virus has caused five waves of human infections since 2013. However, human infections have almost disappeared in the past year. In a recent study, Shi et al. revealed that the usage of a bivalent H5/H7 vaccine successfully prevented chicken infections, and thus prevented, and nearly eliminated, human infections.}, } @article {pmid30472119, year = {2019}, author = {Brokhman, I and Xu, J and Coles, BLK and Razavi, R and Engert, S and Lickert, H and Babona-Pilipos, R and Morshead, CM and Sibley, E and Chen, C and van der Kooy, D}, title = {Dual embryonic origin of the mammalian enteric nervous system.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {256-270}, doi = {10.1016/j.ydbio.2018.11.014}, pmid = {30472119}, issn = {1095-564X}, abstract = {The enteric nervous system is thought to originate solely from the neural crest. Transgenic lineage tracing revealed a novel population of clonal pancreatic duodenal homeobox-1 (Pdx1)-Cre lineage progenitor cells in the tunica muscularis of the gut that produced pancreatic descendants as well as neurons upon differentiation in vitro. Additionally, an in vivo subpopulation of endoderm lineage enteric neurons, but not glial cells, was seen especially in the proximal gut. Analysis of early transgenic embryos revealed Pdx1-Cre progeny (as well as Sox-17-Cre and Foxa2-Cre progeny) migrating from the developing pancreas and duodenum at E11.5 and contributing to the enteric nervous system. These results show that the mammalian enteric nervous system arises from both the neural crest and the endoderm. Moreover, in adult mice there are separate Wnt1-Cre neural crest stem cells and Pdx1-Cre pancreatic progenitors within the muscle layer of the gut.}, } @article {pmid30471843, year = {2019}, author = {Kushida, Y and Reimer, JD}, title = {Molecular phylogeny and diversity of sea pens (Cnidaria: Octocorallia: Pennatulacea) with a focus on shallow water species of the northwestern Pacific Ocean.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {233-244}, doi = {10.1016/j.ympev.2018.10.032}, pmid = {30471843}, issn = {1095-9513}, abstract = {The order Pennatulacea, commonly known as sea pens, are colony-forming benthos belonging within subclass Octocorallia (Anthozoa, Cnidaria). Sea pens are found worldwide from shallow to deep waters, and they are important components in sandy and muddy environments. Thus far, there has been only one molecular study focusing on the phylogenetic relationships within the order Pennatulacea, which mainly treated deep-sea species, and thus information on shallow water species is still lacking. On a regional scale, the diversity of sea pens in the northwestern Pacific, including Japan and Palau, has not been well investigated. In this research, we aimed to: (1) more accurately resolve the phylogenetic relationships of sea pens with the inclusion of shallow water species, and (2) obtain a better understanding of the diversity of sea pens in Japan and Palau. Specimens were collected by SCUBA and dredging from the Ryukyu Islands in southern Japan, and from mainland Japan and Palau, and identified to at least the genus level by their morphological traits. Construction of phylogenetic trees with concatenated sequences including the mitochondrial mutS-like protein DNA mismatch repair gene mtMutS and the NADH dehydrogenase subunit 2 ND2 region were performed. The p-distances of mtMutS were calculated for estimation of species number following McFadden et al. (2011). Molecular data for 12 families and 20 genera of sea pens were used in this study. This most comprehensive study including shallow water taxa provided us with more knowledge of phylogenetic relationships. The resulting phylogenetic trees showed a topology distinguished by four large clades (clades 1-4). Families Veretillidae and Echinoptilidae are shown as not the earliest-diverging taxa. Virgulariidae and Scleroptilidae are shown as polyphyletic groups, and our results reconfirm that families Pennatulidae, Kophobelemnidae and Umbellulidae are not monophyletic groups. Overall, we collected and examined an estimated 18 species from the Ryukyu Islands, 16 species from mainland Japan, and five species from Palau. Some of these specimens represented new records from Ryukyu Islands and Palau. Previous records of these sea pens did not exist likely due to a lack of diversity research in sandy and muddy areas. These results demonstrate that many sea pens discoveries likely remain in shallow waters of the Pacific.}, } @article {pmid30471267, year = {2018}, author = {Racioppi, C and Coppola, U and Christiaen, L and Ristoratore, F}, title = {Transcriptional regulation of Rab32/38, a specific marker of pigment cell formation in Ciona robusta.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.11.013}, pmid = {30471267}, issn = {1095-564X}, abstract = {Through a myriad of pigments stored in different cells, animal pigmentation represents a crucial process to face disparate environmental and ecological challenges. In vertebrates, the small GTPase Rab32 and Rab38 have a conserved role in the transport of key melanogenic enzymes, as tyrosinase (tyr) and tyrosinase-related protein (tyrp), to the melanosomes in formation. We provide a survey on Rab32/38 evolution and its regulatory logics during pigment cell formation in Ciona robusta. Our phylogeny supports the existence of a single Rab32/38 gene in tunicates, which is probably the unique transporter for tyrosinase family members in this clade. Different deletions allow us to identify the minimal cis-regulatory element able to recapitulate the endogenous gene expression during pigment cell development in C. robusta. In this conserved region, we identified two putative binding sites for the transcription factor Mitf, which is known for its role as regulator of pigmentation in vertebrates. Mutational analysis revealed that both Mitf binding sites are essential for the activity of this regulatory region and we demonstrated that Mitf misexpression is able to induce ectopic activation of the Rab32/38 regulatory region in vivo. Our results strongly indicate that Mitf is involved in the regulation of Rab32/38 activity during Ciona pigment cell development.}, } @article {pmid30471266, year = {2018}, author = {Zeng, F and Wunderer, J and Salvenmoser, W and Hess, MW and Ladurner, P and Rothbächer, U}, title = {Papillae revisited and the nature of the adhesive secreting collocytes.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.11.012}, pmid = {30471266}, issn = {1095-564X}, abstract = {Ascidian papillae (palps) constitute a transient sensory adhesive organ that assures larval settlement and the onset of metamorphosis to the filterfeeding adult. Despite the importance of papillae for the ascidian development, their cellular composition is only roughly described. For Ciona intestinalis/robusta, a clear definition of cell numbers and discriminative molecular markers for the different cell types is missing. While some attention was given to neural cell types and their connectivity little is known about the adhesive producing collocytes. We converge serial-section electron microscopy and confocal imaging with various marker combinations to document the 3D organization of the Ciona papillae. We show the papillar development with 4 axial columnar cells (ACCs), 4 lateral primary sensory neurons (PSNs) and 12 central collocytes (CCs). We propose molecular markers for each cell type including novel ones for collocytes. The subcellular characteristics are suggestive of their role in papillar function: the ACCs featuring apical protrusions and microvilli, also contain neuroactive and endocytic vesicles indicative of a chemosensory role. They are clearly distinct from the ciliated glutamatergic PSNs. CCs encircle the ACCs and contain microvilli, small endocytic vesicles and notably a large numbers of adhesive granules that, according to element analysis and histochemistry, contain glycoproteins. Interestingly, we detect two different types of collocyte granules, one of them containing fibrous material and larger quantities of polysaccharides. Consistently, carbohydrate specific lectins label the papillar apex, the granules within CCs and the adhesive plaques upon larval attachment. We further propose CCs to derive from an evolutionary ancient neurosecretory cell type. Our findings contribute to understanding the development of the anterior ('new head') region of the Ciona larva and notably the adhesive secreting cells which has implications for developmental biology, cell differentiation and evolution, but also bioadhesion.}, } @article {pmid30470486, year = {2019}, author = {Gjelsvik, KJ and Besen-McNally, R and Losick, VP}, title = {Solving the Polyploid Mystery in Health and Disease.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {6-14}, doi = {10.1016/j.tig.2018.10.005}, pmid = {30470486}, issn = {0168-9525}, abstract = {Polyploidy (the more than doubling of a cell's genome) frequently arises during organogenesis, tissue repair, and age-associated diseases. Despite its prevalence, major gaps exist in how polyploid cells emerge and affect tissue function. Studies have begun to elucidate the signals required for polyploid cell growth as well as the advantages and disadvantages of polyploidy in health and disease. This review highlights the recent advances on the role and regulation of polyploidy in Drosophila and vertebrate models. The newly discovered versatility of polyploid cells has the potential to provide alternative strategies to promote tissue growth and repair, while limiting disease and dysfunction.}, } @article {pmid30470485, year = {2019}, author = {Al-Barghouthi, BM and Farber, CR}, title = {Dissecting the Genetics of Osteoporosis using Systems Approaches.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {55-67}, doi = {10.1016/j.tig.2018.10.004}, pmid = {30470485}, issn = {0168-9525}, support = {R01 AR064790/AR/NIAMS NIH HHS/United States ; R01 AR068345/AR/NIAMS NIH HHS/United States ; R01 AR071657/AR/NIAMS NIH HHS/United States ; T32 LM012416/LM/NLM NIH HHS/United States ; }, abstract = {Osteoporosis is a condition characterized by low bone mineral density (BMD) and an increased risk of fracture. Traits contributing to osteoporotic fracture are highly heritable, indicating that a comprehensive understanding of bone requires a thorough understanding of the genetic basis of bone traits. Towards this goal, genome-wide association studies (GWASs) have identified over 500 loci associated with bone traits. However, few of the responsible genes have been identified, and little is known of how these genes work together to influence systems-level bone function. In this review, we describe how systems genetics approaches can be used to fill these knowledge gaps.}, } @article {pmid30470199, year = {2018}, author = {Procházka, E and Michalková, V and Daubnerová, I and Roller, L and Klepsatel, P and Žitňan, D and Tsiamis, G and Takáč, P}, title = {Gene expression in reproductive organs of tsetse females - initial data in an approach to reduce fecundity.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {144}, pmid = {30470199}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies are vectors of African trypanosomes, and their vectorial capacity results in a major public health emergency and vast economic losses in sub-Saharan Africa. Given the limited ability of trypanosome prevention and eradication, tsetse vectors remain major targets of control efforts. Larvae of all three instars are developed in mothers' uteri, nourished through milk, and 'larviposited' shortly before pupation. The past few years have witnessed the emergence of approaches based on knockdown of genes involved in milk production, resulting in a significant reduction of fecundity.

RESULTS: In order to identify further genes applicable in the control of tsetse flies, we determined the expression of protein-coding genes in ovaries and uteri from both virgin and heavily pregnant Glossina morsitans morsitans females. Comparison of expression profiles allowed us to identify candidate genes with increased expression in pregnant individuals. Lists with the highest increases include genes involved in oocyte and embryonic development, or nourishment. Maximum ovarian fold change does not exceed 700, while the highest uterine fold change reaches to more than 4000. Relatively high fold changes of two neuropeptide receptors (for corazonin and myosuppressin) propose the corresponding genes alternative targets.

CONCLUSIONS: Given the higher fold changes in the uterus, targeting gene expression in this tissue may result in a more evident reduction of fecundity. However, ovaries should not be neglected, as manifested by several genes with top fold changes involved in early developmental stages. Apart from focusing on the highest fold changes, neuropeptide receptors with moderate increases in expression should be also verified as targets, given their roles in mediating the tissue control. However, this data needs to be considered initial, and the potential of these genes in affecting female fecundity needs to be verified experimentally.}, } @article {pmid30470198, year = {2018}, author = {Scolari, F and Attardo, GM and Aksoy, E and Weiss, B and Savini, G and Takac, P and Abd-Alla, A and Parker, AG and Aksoy, S and Malacrida, AR}, title = {Symbiotic microbes affect the expression of male reproductive genes in Glossina m. morsitans.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {169}, pmid = {30470198}, issn = {1471-2180}, support = {R21 AI109263/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Tsetse flies (Diptera, Glossinidae) display unique reproductive biology traits. Females reproduce through adenotrophic viviparity, nourishing the growing larva into their modified uterus until parturition. Males transfer their sperm and seminal fluid, produced by both testes and male accessory glands, in a spermatophore capsule transiently formed within the female reproductive tract upon mating. Both sexes are obligate blood feeders and have evolved tight relationships with endosymbionts, already shown to provide essential nutrients lacking in their diet. However, the partnership between tsetse and its symbionts has so far been investigated, at the molecular, genomic and metabolomics level, only in females, whereas the roles of microbiota in male reproduction are still unexplored.

RESULTS: Here we begin unravelling the impact of microbiota on Glossina m. morsitans (G. morsitans) male reproductive biology by generating transcriptomes from the reproductive tissues of males deprived of their endosymbionts (aposymbiotic) via maternal antibiotic treatment and dietary supplementation. We then compared the transcriptional profiles of genes expressed in the male reproductive tract of normal and these aposymbiotic flies. We showed that microbiota removal impacts several male reproductive genes by depressing the activity of genes in the male accessory glands (MAGs), including sequences encoding seminal fluid proteins, and increasing expression of genes in the testes. In the MAGs, in particular, the expression of genes related to mating, immunity and seminal fluid components' synthesis is reduced. In the testes, the absence of symbionts activates genes involved in the metabolic apparatus at the basis of male reproduction, including sperm production, motility and function.

CONCLUSIONS: Our findings mirrored the complementary roles male accessory glands and testes play in supporting male reproduction and open new avenues for disentangling the interplay between male insects and endosymbionts. From an applied perspective, unravelling the metabolic and functional relationships between tsetse symbionts and male reproductive physiology will provide fundamental information useful to understanding the biology underlying improved male reproductive success in tsetse. This information is of particular importance in the context of tsetse population control via Sterile Insect Technique (SIT) and its impact on trypanosomiasis transmission.}, } @article {pmid30470197, year = {2018}, author = {Shaida, SS and Weber, JS and Gbem, TT and Ngomtcho, SCH and Musa, UB and Achukwi, MD and Mamman, M and Ndams, IS and Nok, JA and Kelm, S}, title = {Diversity and phylogenetic relationships of Glossina populations in Nigeria and the Cameroonian border region.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {180}, pmid = {30470197}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies are vectors of trypanosomes, parasites that cause devastating disease in humans and livestock. In the course of vector control programmes it is necessary to know about the Glossina species present in the study area, the population dynamics and the genetic exchange between tsetse fly populations.

RESULTS: To achieve an overview of the tsetse fly diversity in Nigeria and at the Nigeria-Cameroon border, tsetse flies were trapped and collected between February and March 2014 and December 2016. Species diversity was determined morphologically and by analysis of Cytochrome C Oxidase SU1 (COI) gene sequences. Internal transcribed spacer-1 (ITS-1) sequences were compared to analyse variations within populations. The most dominant species were G. m. submorsitans, G. tachinoides and G. p. palpalis. In Yankari Game Reserve and Kainji Lake National Park, G. submorsitans and G. tachinoides were most frequent, whereas in Old Oyo National Park and Ijah Gwari G. p. palpalis was the dominant species. Interestingly, four unidentified species were recorded during the survey, for which no information on COI or ITS-1 sequences exists. G. p. palpalis populations showed a segregation in two clusters along the Cameroon-Nigerian border.

CONCLUSIONS: The improved understanding of the tsetse populations in Nigeria will support decisions on the scale in which vector control is likely to be more effective. In order to understand in more detail how isolated these populations are, it is recommended that further studies on gene flow be carried out using other markers, including microsatellites.}, } @article {pmid30470196, year = {2018}, author = {Doudoumis, V and Augustinos, A and Saridaki, A and Parker, A and Abd-Alla, AMM and Bourtzis, K and Tsiamis, G}, title = {Different laboratory populations similar bacterial profile? The case of Glossina palpalis gambiensis.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {148}, pmid = {30470196}, issn = {1471-2180}, abstract = {BACKGROUND: Microbiota plays an important role in the biology, ecology and evolution of insects including tsetse flies. The bacterial profile of 3 Glossina palpalis gambiensis laboratory colonies was examined using 16S rRNA gene amplicon sequencing to evaluate the dynamics of the bacterial diversity within and between each G. p. gambiensis colony.

RESULTS: The three G. p. gambiensis laboratory colonies displayed similar bacterial diversity indices and OTU distribution. Larval guts displayed a higher diversity when compared with the gastrointestinal tract of adults while no statistically significant differences were observed between testes and ovaries. Wigglesworthia and Sodalis were the most dominant taxa. In more detail, the gastrointestinal tract of adults was more enriched by Wigglesworthia while Sodalis were prominent in gonads. Interestingly, in larval guts a balanced co-existence between Wigglesworthia and Sodalis was observed. Sequences assigned to Wolbachia, Propionibacterium, and Providencia were also detected but to a much lesser degree. Clustering analysis indicated that the bacterial profile in G. p. gambiensis exhibits tissue tropism, hence distinguishing the gut bacterial profile from that present in reproductive organs.

CONCLUSIONS: Our results indicated that age, gender and the origin of the laboratory colonies did not significantly influence the formation of the bacterial profile, once these populations were kept under the same rearing conditions. Within the laboratory populations a tissue tropism was observed between the gut and gonadal bacterial profile.}, } @article {pmid30470195, year = {2018}, author = {Meki, IK and Kariithi, HM and Parker, AG and Vreysen, MJB and Ros, VID and Vlak, JM and van Oers, MM and Abd-Alla, AMM}, title = {RNA interference-based antiviral immune response against the salivary gland hypertrophy virus in Glossina pallidipes.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {170}, pmid = {30470195}, issn = {1471-2180}, abstract = {BACKGROUND: Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; Hytrosaviridae) is a non-occluded dsDNA virus that specifically infects the adult stages of the hematophagous tsetse flies (Glossina species, Diptera: Glossinidae). GpSGHV infections are usually asymptomatic, but unknown factors can result to a switch to acute symptomatic infection, which is characterized by the salivary gland hypertrophy (SGH) syndrome associated with decreased fecundity that can ultimately lead to a colony collapse. It is uncertain how GpSGHV is maintained amongst Glossina spp. populations but RNA interference (RNAi) machinery, a conserved antiviral defense in insects, is hypothesized to be amongst the host's mechanisms to maintain the GpSGHV in asymptomatic (persistent or latent) infection state. Here, we investigated the involvement of RNAi during GpSGHV infections by comparing the expression of three key RNAi machinery genes, Dicer (DCR), Argonaute (AGO) and Drosha, in artificially virus injected, asymptomatic and symptomatic infected G. pallidipes flies compared to PBS injected (controls) individuals. We further assessed the impact of AGO2 knockdown on virus infection by RT-qPCR quantification of four selected GpSGHV genes, i.e. odv-e66, dnapol, maltodextrin glycosyltransferase (a tegument gene) and SGHV091 (a capsid gene).

RESULTS: We show that in response to hemocoelic injections of GpSGHV into G. pallidipes flies, increased virus replication was accompanied by significant upregulation of the expression of three RNAi key genes; AGO1, AGO2 and DCR2, and a moderate increase in the expression of Drosha post injection compared to the PBS-injected controls. Furthermore, compared to asymptomatically infected individuals, symptomatic flies showed significant downregulation of AGO1, AGO2 and Drosha, but a moderate increase in the expression of DCR2. Compared to the controls, knockdown of AGO2 did not have a significant impact on virus infection in the flies as evidenced by unaltered transcript levels of the selected GpSGHV genes.

CONCLUSION: The upregulation of the expression of the RNAi genes implicate involvement of this machinery in controlling GpSGHV infections and the establishment of symptomatic GpSGHV infections in Glossina. These findings provide a strategic foundation to understand GpSGHV infections and to control latent (asymptomatic) infections in Glossina spp. and thereby control SGHVs in insect production facilities.}, } @article {pmid30470194, year = {2018}, author = {Hatzig, SV and Nuppenau, JN and Snowdon, RJ and Schießl, SV}, title = {Drought stress has transgenerational effects on seeds and seedlings in winter oilseed rape (Brassica napus L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {297}, pmid = {30470194}, issn = {1471-2229}, support = {SN14/14-2//Deutsche Forschungsgemeinschaft/ ; 031A549A//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Brassica napus/genetics/*physiology ; *Droughts ; Epigenesis, Genetic ; Germination ; Inheritance Patterns ; Seedlings/genetics/growth & development ; *Seeds/genetics/growth & development ; *Stress, Physiological ; }, abstract = {BACKGROUND: Drought stress has a negative effect on both seed yield and seed quality in Brassica napus (oilseed rape, canola). Here we show that while drought impairs the maternal plant performance, it also increases the vigour of progeny of stressed maternal plants. We investigated the transgenerational influence of abiotic stress by detailed analysis of yield, seed quality, and seedling performance on a growth-related and metabolic level. Seeds of eight diverse winter oilseed rape genotypes were generated under well-watered and drought stress conditions under controlled-environment conditions in large plant containers.

RESULTS: We found a decrease in seed quality in seeds derived from mother plants that were exposed to drought stress. At the same time, the seeds that developed under stress conditions showed higher seedling vigour compared to non-stressed controls.This effect on seed quality and seedling vigour was found to be independent of maternal plant yield performance.

CONCLUSIONS: Drought stress has a positive transgenerational effect on seedling vigour. Three potential causes for stress-induced improvement of seedling vigour are discussed: (1) Heterotic effects caused by a tendency towards a higher outcrossing rate in response to stress; (2) an altered reservoir of seed storage metabolites to which the seedling resorts during early growth, and (3) inter-generational stress memory, formed by stress-induced changes in the epigenome of the seedling.}, } @article {pmid30470193, year = {2018}, author = {Santana, JO and Gramacho, KP and de Souza Eduvirgens Ferreira, KT and Rezende, RP and Mangabeira, PAO and Dias, RPM and Couto, FM and Pirovani, CP}, title = {Witches' broom resistant genotype CCN51 shows greater diversity of symbiont bacteria in its phylloplane than susceptible genotype catongo.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {194}, pmid = {30470193}, issn = {1471-2180}, abstract = {BACKGROUND: Theobroma cacao L. (cacao) is a perennial tropical tree, endemic to rainforests of the Amazon Basin. Large populations of bacteria live on leaf surfaces and these phylloplane microorganisms can have important effects on plant health. In recent years, the advent of high-throughput sequencing techniques has greatly facilitated studies of the phylloplane microbiome. In this study, we characterized the bacterial microbiome of the phylloplane of the catongo genotype (susceptible to witch's broom) and CCN51 (resistant). Bacterial microbiome was determined by sequencing the V3-V4 region of the bacterial 16S rRNA gene.

RESULTS: After the pre-processing, a total of 1.7 million reads were considered. In total, 106 genera of bacteria were characterized. Proteobacteria was the predominant phylum in both genotypes. The exclusive genera of Catongo showed activity in the protection against UV radiation and in the transport of substrates. CCN51 presented genus that act in the biological control and inhibition in several taxonomic groups. Genotype CCN51 presented greater diversity of microorganisms in comparison to the Catongo genotype and the total community was different between both. Scanning electron microscopy analysis of leaves revealed that on the phylloplane, many bacterial occur in large aggregates in several regions of the surface and isolated nearby to the stomata.

CONCLUSIONS: We describe for the first time the phylloplane bacterial communities of T. cacao. The Genotype CCN51, resistant to the witch's broom, has a greater diversity of bacterial microbioma in comparison to Catongo and a greater amount of exclusive microorganisms in the phylloplane with antagonistic action against phytopathogens.}, } @article {pmid30470192, year = {2018}, author = {Malele, I and Nyingilili, H and Lyaruu, E and Tauzin, M and Bernard Ollivier, B and Cayol, JL and Fardeau, ML and Geiger, A}, title = {Bacterial diversity obtained by culturable approaches in the gut of Glossina pallidipes population from a non sleeping sickness focus in Tanzania: preliminary results.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {164}, pmid = {30470192}, issn = {1471-2180}, abstract = {BACKGROUND: Glossina pallidipes is a haematophagous insect that serves as a cyclic transmitter of trypanosomes causing African Trypanosomiasis (AT). To fully assess the role of G. pallidipes in the epidemiology of AT, especially the human form of the disease (HAT), it is essential to know the microbial diversity inhabiting the gut of natural fly populations. This study aimed to examine the diversity of G. pallidipes fly gut bacteria by culture-dependent approaches.

RESULTS: 113 bacterial isolates were obtained from aerobic and anaerobic microorganisms originating from the gut of G. pallidipes. 16S rDNA of each isolate was PCR amplified and sequenced. The overall majority of identified bacteria belonged in descending order to the Firmicutes (86.6%), Actinobacteria (7.6%), Proteobacteria (5.5%)and Bacteroidetes (0.3%). Diversity of Firmicutes was found higher when enrichments and isolation were performed under anaerobic conditions than aerobic ones. Experiments conducted in the absence of oxygen (anaerobiosis) led to the isolation of bacteria pertaining to four phyla (83% Firmicutes, 15% Actinobacteria, 1% Proteobacteria and 0.5% Bacteroidetes, whereas those conducted in the presence of oxygen (aerobiosis) led to the isolation of bacteria affiliated to two phyla only (90% Firmicutes and 10% Proteobacteria). Phylogenetic analyses placed these isolates into 11 genera namely Bacillus, Acinetobacter, Mesorhizobium, Paracoccus, Microbacterium, Micrococcus, Arthrobacter, Corynobacterium, Curtobacterium, Vagococcus and Dietzia spp.which are known to be either facultative anaerobes, aerobes, or even microaerobes.

CONCLUSION: This study shows that G. pallidipes fly gut is an environmental reservoir for a vast number of bacterial species, which are likely to be important for ecological microbial well being of the fly and possibly on differing vectorial competence and refractoriness against AT epidemiology.}, } @article {pmid30470191, year = {2018}, author = {Meki, IK and Kariithi, HM and Ahmadi, M and Parker, AG and Vreysen, MJB and Vlak, JM and van Oers, MM and Abd-Alla, AMM}, title = {Hytrosavirus genetic diversity and eco-regional spread in Glossina species.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {143}, pmid = {30470191}, issn = {1471-2180}, abstract = {BACKGROUND: The management of the tsetse species Glossina pallidipes (Diptera; Glossinidae) in Africa by the sterile insect technique (SIT) has been hindered by infections of G. pallidipes production colonies with Glossina pallidipes salivary gland hypertrophy virus (GpSGHV; Hytrosaviridae family). This virus can significantly decrease productivity of the G. pallidipes colonies. Here, we used three highly diverged genes and two variable number tandem repeat regions (VNTRs) of the GpSGHV genome to identify the viral haplotypes in seven Glossina species obtained from 29 African locations and determine their phylogenetic relatedness.

RESULTS: GpSGHV was detected in all analysed Glossina species using PCR. The highest GpSGHV prevalence was found in G. pallidipes colonized at FAO/IAEA Insect Pest Control Laboratory (IPCL) that originated from Uganda (100%) and Tanzania (88%), and a lower prevalence in G. morsitans morsitans from Tanzania (58%) and Zimbabwe (20%). Whereas GpSGHV was detected in 25-40% of G. fuscipes fuscipes in eastern Uganda, the virus was not detected in specimens of neighboring western Kenya. Most of the identified 15 haplotypes were restricted to specific Glossina species in distinct locations. Seven haplotypes were found exclusively in G. pallidipes. The reference haplotype H1 (GpSGHV-Uga; Ugandan strain) was the most widely distributed, but was not found in G. swynnertoni GpSGHV. The 15 haplotypes clustered into three distinct phylogenetic clades, the largest contained seven haplotypes, which were detected in six Glossina species. The G. pallidipes-infecting haplotypes H10, H11 and H12 (from Kenya) clustered with H7 (from Ethiopia), which presumably corresponds to the recently sequenced GpSGHV-Eth (Ethiopian) strain. These four haplotypes diverged the most from the reference H1 (GpSGHV-Uga). Haplotypes H1, H5 and H14 formed three main genealogy hubs, potentially representing the ancestors of the 15 haplotypes.

CONCLUSION: These data identify G. pallidipes as a significant driver for the generation and diversity of GpSGHV variants. This information may provide control guidance when new tsetse colonies are established and hence, for improved management of the virus in tsetse rearing facilities that maintain multiple Glossina species.}, } @article {pmid30470190, year = {2018}, author = {Augustinos, AA and Meki, IK and Demirbas-Uzel, G and Ouédraogo, GMS and Saridaki, A and Tsiamis, G and Parker, AG and Abd-Alla, AMM and Bourtzis, K}, title = {Nuclear and Wolbachia-based multimarker approach for the rapid and accurate identification of tsetse species.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {147}, pmid = {30470190}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies (Diptera: Glossinidae) are solely responsible for the transmission of African trypanosomes, causative agents of sleeping sickness in humans and nagana in livestock. Due to the lack of efficient vaccines and the emergence of drug resistance, vector control approaches such as the sterile insect technique (SIT), remain the most effective way to control disease. SIT is a species-specific approach and therefore requires accurate identification of natural pest populations at the species level. However, the presence of morphologically similar species (species complexes and sub-species) in tsetse flies challenges the successful implementation of SIT-based population control.

RESULTS: In this study, we evaluate different molecular tools that can be applied for the delimitation of different Glossina species using tsetse samples derived from laboratory colonies, natural populations and museum specimens. The use of mitochondrial markers, nuclear markers (including internal transcribed spacer 1 (ITS1) and different microsatellites), and bacterial symbiotic markers (Wolbachia infection status) in combination with relatively inexpensive techniques such as PCR, agarose gel electrophoresis, and to some extent sequencing provided a rapid, cost effective, and accurate identification of several tsetse species.

CONCLUSIONS: The effectiveness of SIT benefits from the fine resolution of species limits in nature. The present study supports the quick identification of large samples using simple and cost effective universalized protocols, which can be easily applied by countries/laboratories with limited resources and expertise.}, } @article {pmid30470189, year = {2018}, author = {Hu, Y and Bai, C and Cai, J and Shao, K and Tang, X and Gao, G}, title = {Low recovery of bacterial community after an extreme salinization-desalinization cycle.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {195}, pmid = {30470189}, issn = {1471-2180}, support = {2013ZX07104-004//National Water Pollution Control and Management of Science and Technology Major Projects/ ; 41171388//National Natural Science Foundation of China/ ; 41471040//National Natural Science Foundation of China/ ; 41501101//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Understanding the recovery of bacterial communities after extreme environmental disturbances offers key opportunities to investigate ecosystem resilience. However, it is not yet clear whether bacterial communities can rebound to their pre-disturbance levels. To shed light on this issue, we tracked the responses of bacterial communities during an extreme salinization-desalinization cycle.

RESULTS: Our results showed that salinization-up process induced an ecological succession, shifting from a community dominated by Betaproteobacteria to Gammaproteobacteria. Within the desalinization-down process, taxon-specific recovery trajectories varied profoundly, with only Gammaproteobacteria returning to their initial levels, of which Alphaproteobacteria was the most prominent member. The α-diversity indices gradually increased at oligosaline environment (0.03‰ to 3‰) and subsequently decreased profoundly at hypersaline condition (10‰ to 90‰). However, the indices did not return to pre-disturbance level along the previous trajectory observed during the desalinization. Approximately half of the original OTUs were not detected during desalinization, suggesting that the seed bank may be damaged by the hypersaline environment. Moreover, Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) implied that the osmosensors' capacity of bacterial communities was also impaired by the hypersaline condition.

CONCLUSIONS: These results suggested that the bacterial communities showed a low recovery after the extreme salinization-desalinization cycle.}, } @article {pmid30470188, year = {2018}, author = {Engl, T and Michalkova, V and Weiss, BL and Uzel, GD and Takac, P and Miller, WJ and Abd-Alla, AMM and Aksoy, S and Kaltenpoth, M}, title = {Effect of antibiotic treatment and gamma-irradiation on cuticular hydrocarbon profiles and mate choice in tsetse flies (Glossina m. morsitans).}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {145}, pmid = {30470188}, issn = {1471-2180}, abstract = {BACKGROUND: Symbiotic microbes represent a driving force of evolutionary innovation by conferring novel ecological traits to their hosts. Many insects are associated with microbial symbionts that contribute to their host's nutrition, digestion, detoxification, reproduction, immune homeostasis, and defense. In addition, recent studies suggest a microbial involvement in chemical communication and mating behavior, which can ultimately impact reproductive isolation and, hence, speciation. Here we investigated whether a disruption of the microbiota through antibiotic treatment or irradiation affects cuticular hydrocarbon profiles, and possibly mate choice behavior in the tsetse fly, Glossina morsitans morsitans. Four independent experiments that differentially knock down the multiple bacterial symbionts of tsetse flies were conducted by subjecting tsetse flies to ampicillin, tetracycline, or gamma-irradiation and analyzing their cuticular hydrocarbon profiles in comparison to untreated controls by gas chromatography - mass spectrometry. In two of the antibiotic experiments, flies were mass-reared, while individual rearing was done for the third experiment to avoid possible chemical cross-contamination between individual flies.

RESULTS: All three antibiotic experiments yielded significant effects of antibiotic treatment (particularly tetracycline) on cuticular hydrocarbon profiles in both female and male G. m. morsitans, while irradiation itself had no effect on the CHC profiles. Importantly, tetracycline treatment reduced relative amounts of 15,19,23-trimethyl-heptatriacontane, a known compound of the female contact sex pheromone, in two of the three experiments, suggesting a possible implication of microbiota disturbance on mate choice decisions. Concordantly, both female and male flies preferred non-treated over tetracycline-treated flies in direct choice assays.

CONCLUSIONS: While we cannot exclude the possibility that antibiotic treatment had a directly detrimental effect on fly vigor as we are unable to recolonize antibiotic treated flies with individual symbiont taxa, our results are consistent with an effect of the microbiota, particularly the obligate nutritional endosymbiont Wigglesworthia, on CHC profiles and mate choice behavior. These findings highlight the importance of considering host-microbiota interactions when studying chemical communication and mate choice in insects.}, } @article {pmid30470187, year = {2018}, author = {Ouedraogo, GMS and Demirbas-Uzel, G and Rayaisse, JB and Gimonneau, G and Traore, AC and Avgoustinos, A and Parker, AG and Sidibe, I and Ouedraogo, AG and Traore, A and Bayala, B and Vreysen, MJB and Bourtzis, K and Abd-Alla, AMM}, title = {Prevalence of trypanosomes, salivary gland hypertrophy virus and Wolbachia in wild populations of tsetse flies from West Africa.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {153}, pmid = {30470187}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies are vectors of African trypanosomes, protozoan parasites that cause sleeping sickness (or human African trypanosomosis) in humans and nagana (or animal African trypanosomosis) in livestock. In addition to trypanosomes, four symbiotic bacteria Wigglesworthia glossinidia, Sodalis glossinidius, Wolbachia, Spiroplasma and one pathogen, the salivary gland hypertrophy virus (SGHV), have been reported in different tsetse species. We evaluated the prevalence and coinfection dynamics between Wolbachia, trypanosomes, and SGHV in four tsetse species (Glossina palpalis gambiensis, G. tachinoides, G. morsitans submorsitans, and G. medicorum) that were collected between 2008 and 2015 from 46 geographical locations in West Africa, i.e. Burkina Faso, Mali, Ghana, Guinea, and Senegal.

RESULTS: The results indicated an overall low prevalence of SGHV and Wolbachia and a high prevalence of trypanosomes in the sampled wild tsetse populations. The prevalence of all three infections varied among tsetse species and sample origin. The highest trypanosome prevalence was found in Glossina tachinoides (61.1%) from Ghana and in Glossina palpalis gambiensis (43.7%) from Senegal. The trypanosome prevalence in the four species from Burkina Faso was lower, i.e. 39.6% in Glossina medicorum, 18.08%; in Glossina morsitans submorsitans, 16.8%; in Glossina tachinoides and 10.5% in Glossina palpalis gambiensis. The trypanosome prevalence in Glossina palpalis gambiensis was lowest in Mali (6.9%) and Guinea (2.2%). The prevalence of SGHV and Wolbachia was very low irrespective of location or tsetse species with an average of 1.7% for SGHV and 1.0% for Wolbachia. In some cases, mixed infections with different trypanosome species were detected. The highest prevalence of coinfection was Trypanosoma vivax and other Trypanosoma species (9.5%) followed by coinfection of T. congolense with other trypanosomes (7.5%). The prevalence of coinfection of T. vivax and T. congolense was (1.0%) and no mixed infection of trypanosomes, SGHV and Wolbachia was detected.

CONCLUSION: The results indicated a high rate of trypanosome infection in tsetse wild populations in West African countries but lower infection rate of both Wolbachia and SGHV. Double or triple mixed trypanosome infections were found. In addition, mixed trypanosome and SGHV infections existed however no mixed infections of trypanosome and/or SGHV with Wolbachia were found.}, } @article {pmid30470186, year = {2018}, author = {Kariithi, HM and Boucias, DG and Murungi, EK and Meki, IK and Demirbaş-Uzel, G and van Oers, MM and Vreysen, MJB and Abd-Alla, AMM and Vlak, JM}, title = {Coevolution of hytrosaviruses and host immune responses.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {183}, pmid = {30470186}, issn = {1471-2180}, abstract = {BACKGROUND: Hytrosaviruses (SGHVs; Hytrosaviridae family) are double-stranded DNA (dsDNA) viruses that cause salivary gland hypertrophy (SGH) syndrome in flies. Two structurally and functionally distinct SGHVs are recognized; Glossina pallidipes SGHV (GpSGHV) and Musca domestica SGHV (MdSGHV), that infect the hematophagous tsetse fly and the filth-feeding housefly, respectively. Genome sizes and gene contents of GpSGHV (~ 190 kb; 160-174 genes) and MdSGHV (~ 124 kb; 108 genes) may reflect an evolution with the SGHV-hosts resulting in differences in pathobiology. Whereas GpSGHV can switch from asymptomatic to symptomatic infections in response to certain unknown cues, MdSGHV solely infects symptomatically. Overt SGH characterizes the symptomatic infections of SGHVs, but whereas MdSGHV induces both nuclear and cellular hypertrophy (enlarged non-replicative cells), GpSGHV induces cellular hyperplasia (enlarged replicative cells). Compared to GpSGHV's specificity to Glossina species, MdSGHV infects other sympatric muscids. The MdSGHV-induced total shutdown of oogenesis inhibits its vertical transmission, while the GpSGHV's asymptomatic and symptomatic infections promote vertical and horizontal transmission, respectively. This paper reviews the coevolution of the SGHVs and their hosts (housefly and tsetse fly) based on phylogenetic relatedness of immune gene orthologs/paralogs and compares this with other virus-insect models.

RESULTS: Whereas MdSGHV is not vertically transmitted, GpSGHV is both vertically and horizontally transmitted, and the balance between the two transmission modes may significantly influence the pathogenesis of tsetse virus. The presence and absence of bacterial symbionts (Wigglesworthia and Sodalis) in tsetse and Wolbachia in the housefly, respectively, potentially contributes to the development of SGH symptoms. Unlike MdSGHV, GpSGHV contains not only host-derived proteins, but also appears to have evolutionarily recruited cellular genes from ancestral host(s) into its genome, which, although may be nonessential for viral replication, potentially contribute to the evasion of host's immune responses. Whereas MdSGHV has evolved strategies to counteract both the housefly's RNAi and apoptotic responses, the housefly has expanded its repertoire of immune effector, modulator and melanization genes compared to the tsetse fly.

CONCLUSIONS: The ecologies and life-histories of the housefly and tsetse fly may significantly influence coevolution of MdSGHV and GpSGHV with their hosts. Although there are still many unanswered questions regarding the pathogenesis of SGHVs, and the extent to which microbiota influence expression of overt SGH symptoms, SGHVs are attractive 'explorers' to elucidate the immune responses of their hosts, and the transmission modes of other large DNA viruses.}, } @article {pmid30470185, year = {2018}, author = {Schneider, DI and Parker, AG and Abd-Alla, AM and Miller, WJ}, title = {High-sensitivity detection of cryptic Wolbachia in the African tsetse fly (Glossina spp.).}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {140}, pmid = {30470185}, issn = {1471-2180}, abstract = {BACKGROUND: In African tsetse flies Glossina, spp. detection of bacterial symbionts such as Wolbachia is challenging since their prevalence and distribution are patchy, and natural symbiont titers can range at levels far below detection limit of standard molecular techniques. Reliable estimation of symbiont infection frequency, especially with regard to interrelations between symbionts and their potential impact on host biology, is of pivotal interest in the context of future applications for the control and eradication of Glossina-vectored African trypanosomosis. The presence or absence of symbionts is routinely screened with endpoint polymerase chain reaction (PCR), which has numerous advantages, but reaches its limits, when detecting infections at natural low titer. To not only determine presence of native tsetse symbionts but also to localize them to specific host tissues, fluorescence in situ hybridization (FISH) can be applied. However, classic FISH assays may not detect low-titer infections due to limitations in sensitivity.

RESULTS: We have compared classic endpoint PCR with high-sensitivity blot-PCR. We demonstrate that the latter technique allows for clear detection of low-titer Wolbachia in the morsitans and palpalis groups while classic endpoint PCR does not. In order to localize Wolbachia in situ in high and low-titer Glossina species, we applied high-end Stellaris® rRNA-FISH. We show that with this high sensitivity method, even low amounts of Wolbachia can be traced in specific tissues. Furthermore, we highlight that more tissues and organs than previously recorded are infested with Wolbachia in subspecies of the morsitans and palpalis groups.

CONCLUSIONS: Our results demonstrate that overall symbiont infection frequencies as well as the presence in specific host tissues may be underestimated when using low-sensitivity methods. To better understand the complex interrelation of tsetse flies and their native symbionts plus the pathogenic trypanosomes, it is important to consider application of a broader range of high-sensitivity detection tools.}, } @article {pmid30470184, year = {2018}, author = {Channumsin, M and Ciosi, M and Masiga, D and Turner, CMR and Mable, BK}, title = {Sodalis glossinidius presence in wild tsetse is only associated with presence of trypanosomes in complex interactions with other tsetse-specific factors.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {163}, pmid = {30470184}, issn = {1471-2180}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Susceptibility of tsetse flies (Glossina spp.) to trypanosomes of both humans and animals has been associated with the presence of the endosymbiont Sodalis glossinidius. However, intrinsic biological characteristics of the flies and environmental factors can influence the presence of both S. glossinidius and the parasites. It thus remains unclear whether it is the S. glossinidius or other attributes of the flies that explains the apparent association. The objective of this study was to test whether the presence of Trypanosoma vivax, T. congolense and T. brucei are related to the presence of S. glossinidius in tsetse flies when other factors are accounted for: geographic location, species of Glossina, sex or age of the host flies.

RESULTS: Flies (n = 1090) were trapped from four sites in the Shimba Hills and Nguruman regions in Kenya. Sex and species of tsetse (G. austeni, G. brevipalpis, G. longipennis and G. pallidipes) were determined based on external morphological characters and age was estimated by a wing fray score method. The presence of trypanosomes and S. glossinidius was detected using PCR targeting the internal transcribed spacer region 1 and the haemolysin gene, respectively. Sequencing was used to confirm species identification. Generalised Linear Models (GLMs) and Multiple Correspondence Analysis (MCA) were applied to investigate multivariable associations. The overall prevalence of trypanosomes was 42.1%, but GLMs revealed complex patterns of associations: the presence of S. glossinidius was associated with trypanosome presence but only in interactions with other factors and only in some species of trypanosomes. The strongest association was found for T. congolense, and no association was found for T. vivax. The MCA also suggested only a weak association between the presence of trypanosomes and S. glossinidius. Trypanosome-positive status showed strong associations with sex and age while S. glossinidius-positive status showed a strong association with geographic location and species of fly.

CONCLUSIONS: We suggest that previous conclusions about the presence of endosymbionts increasing probability of trypanosome presence in tsetse flies may have been confounded by other factors, such as community composition of the tsetse flies and the specific trypanosomes found in different regions.}, } @article {pmid30470183, year = {2018}, author = {Geiger, A and Malele, I and Abd-Alla, AM and Njiokou, F}, title = {Blood feeding tsetse flies as hosts and vectors of mammals-pre-adapted African Trypanosoma: current and expected research directions.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {162}, pmid = {30470183}, issn = {1471-2180}, abstract = {Research on the zoo-anthropophilic blood feeding tsetse flies' biology conducted, by different teams, in laboratory settings and at the level of the ecosystems- where also co-perpetuate African Trypanosoma- has allowed to unveil and characterize key features of tsetse flies' bacterial symbionts on which rely both (a) the perpetuation of the tsetse fly populations and (b) the completion of the developmental program of the African Trypanosoma. Transcriptomic analyses have already provided much information on tsetse fly genes as well as on genes of the fly symbiotic partners Sodalis glossinidius and Wigglesworthia, which account for the successful onset or not of the African Trypanosoma developmental program. In parallel, identification of the non- symbiotic bacterial communities hosted in the tsetse fly gut has recently been initiated: are briefly introduced those bacteria genera and species common to tsetse flies collected from distinct ecosystems, that could be further studied as potential biologicals preventing the onset of the African Trypanosoma developmental program. Finally, future work will need to concentrate on how to render tsetse flies refractory, and the best means to disseminate them in the field in order to establish an overall refractory fly population.}, } @article {pmid30470182, year = {2018}, author = {Kariithi, HM and Meki, IK and Schneider, DI and De Vooght, L and Khamis, FM and Geiger, A and Demirbaş-Uzel, G and Vlak, JM and iNCE, IA and Kelm, S and Njiokou, F and Wamwiri, FN and Malele, II and Weiss, BL and Abd-Alla, AMM}, title = {Enhancing vector refractoriness to trypanosome infection: achievements, challenges and perspectives.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {179}, pmid = {30470182}, issn = {1471-2180}, abstract = {With the absence of effective prophylactic vaccines and drugs against African trypanosomosis, control of this group of zoonotic neglected tropical diseases depends the control of the tsetse fly vector. When applied in an area-wide insect pest management approach, the sterile insect technique (SIT) is effective in eliminating single tsetse species from isolated populations. The need to enhance the effectiveness of SIT led to the concept of investigating tsetse-trypanosome interactions by a consortium of researchers in a five-year (2013-2018) Coordinated Research Project (CRP) organized by the Joint Division of FAO/IAEA. The goal of this CRP was to elucidate tsetse-symbiome-pathogen molecular interactions to improve SIT and SIT-compatible interventions for trypanosomoses control by enhancing vector refractoriness. This would allow extension of SIT into areas with potential disease transmission. This paper highlights the CRP's major achievements and discusses the science-based perspectives for successful mitigation or eradication of African trypanosomosis.}, } @article {pmid30470181, year = {2018}, author = {De Vooght, L and Van Keer, S and Van Den Abbeele, J}, title = {Towards improving tsetse fly paratransgenesis: stable colonization of Glossina morsitans morsitans with genetically modified Sodalis.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {165}, pmid = {30470181}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies (Glossina sp.) refractory to trypanosome infection are currently being explored as potential tools to contribute in the control of human and animal African trypanosomiasis. One approach to disrupt trypanosome transmission by the tsetse fly vector involves the use of paratransgenesis, a technique that aims to reduce vector competence of disease vectors via genetic modification of their microbiota. An important prerequisite for developing paratransgenic tsetse flies is the stable repopulation of tsetse flies and their progeny with its genetically modified Sodalis symbiont without interfering with host fitness.

RESULTS: In this study, we assessed by qPCR analysis the ability of a chromosomally GFP-tagged Sodalis (recSodalis) strain to efficiently colonize various tsetse tissues and its transmission to the next generation of offspring using different introduction approaches. When introduced in the adult stage of the fly via thoracic microinjection, recSodalis is maintained at high densities for at least 21 days. However, no vertical transmission to the offspring was observed. Oral administration of recSodalis did not lead to the colonization of either adult flies or their offspring. Finally, introduction of recSodalis via microinjection of third-instar larvae resulted in stably colonized adult tsetse flies. Moreover, the subsequent generations of offspring were also efficiently colonized with recSodalis. We show that proper colonization of the female reproductive tissues by recSodalis is an important determinant for vertical transmission.

CONCLUSIONS: Intralarval microinjection of recSodalis proves to be essential to achieve optimal colonization of flies with genetically modified Sodalis and its subsequent dissemination into the following generations of progeny. This study provides the proof-of-concept that Sodalis can be used to drive expression of exogenous transgenes in Glossina morsitans morsitans colonies representing a valuable contribution to the development of a paratransgenic tsetse fly based control strategy.}, } @article {pmid30470180, year = {2018}, author = {Abd-Alla, AMM and Tsiamis, G and Boucias, DG}, title = {Special issue on enhancing vector refractoriness to trypanosome infection-foreword.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {141}, pmid = {30470180}, issn = {1471-2180}, } @article {pmid30470179, year = {2018}, author = {Demirbas-Uzel, G and De Vooght, L and Parker, AG and Vreysen, MJB and Mach, RL and Van Den Abbeele, J and Abd-Alla, AMM}, title = {Combining paratransgenesis with SIT: impact of ionizing radiation on the DNA copy number of Sodalis glossinidius in tsetse flies.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {160}, pmid = {30470179}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies (Diptera: Glossinidae) are the cyclical vectors of the causative agents of African Trypanosomosis, which has been identified as a neglected tropical disease in both humans and animals in many regions of sub-Saharan Africa. The sterile insect technique (SIT) has shown to be a powerful method to manage tsetse fly populations when used in the frame of an area-wide integrated pest management (AW-IPM) program. To date, the release of sterile males to manage tsetse fly populations has only been implemented in areas to reduce transmission of animal African Trypanosomosis (AAT). The implementation of the SIT in areas with Human African Trypanosomosis (HAT) would require additional measures to eliminate the potential risk associated with the release of sterile males that require blood meals to survive and hence, might contribute to disease transmission. Paratransgenesis offers the potential to develop tsetse flies that are refractory to trypanosome infection by modifying their associated bacteria (Sodalis glossinidius) here after referred to as Sodalis. Here we assessed the feasibility of combining the paratransgenesis approach with SIT by analyzing the impact of ionizing radiation on the copy number of Sodalis and the vectorial capacity of sterilized tsetse males.

RESULTS: Adult Glossina morsitans morsitans that emerged from puparia irradiated on day 22 post larviposition did not show a significant decline in Sodalis copy number as compared with non-irradiated flies. Conversely, the Sodalis copy number was significantly reduced in adults that emerged from puparia irradiated on day 29 post larviposition and in adults irradiated on day 7 post emergence. Moreover, irradiating 22-day old puparia reduced the copy number of Wolbachia and Wigglesworthia in emerged adults as compared with non-irradiated controls, but the radiation treatment had no significant impact on the vectorial competence of the flies.

CONCLUSION: Although the radiation treatment significantly reduced the copy number of some tsetse fly symbionts, the copy number of Sodalis recovered with time in flies irradiated as 22-day old puparia. This recovery offers the opportunity to combine a paratransgenesis approach - using modified Sodalis to produce males refractory to trypanosome infection - with the release of sterile males to minimize the risk of disease transmission, especially in HAT endemic areas. Moreover, irradiation did not increase the vector competence of the flies for trypanosomes.}, } @article {pmid30470178, year = {2018}, author = {Griffith, BC and Weiss, BL and Aksoy, E and Mireji, PO and Auma, JE and Wamwiri, FN and Echodu, R and Murilla, G and Aksoy, S}, title = {Analysis of the gut-specific microbiome from field-captured tsetse flies, and its potential relevance to host trypanosome vector competence.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {146}, pmid = {30470178}, issn = {1471-2180}, support = {D43 TW007391/TW/FIC NIH HHS/United States ; R01 AI051584/AI/NIAID NIH HHS/United States ; R01 AI068932/AI/NIAID NIH HHS/United States ; U01 AI115648/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: The tsetse fly (Glossina sp.) midgut is colonized by maternally transmitted and environmentally acquired bacteria. Additionally, the midgut serves as a niche in which pathogenic African trypanosomes reside within infected flies. Tsetse's bacterial microbiota impacts many aspects of the fly's physiology. However, little is known about the structure of tsetse's midgut-associated bacterial communities as they relate to geographically distinct fly habitats in east Africa and their contributions to parasite infection outcomes. We utilized culture dependent and independent methods to characterize the taxonomic structure and density of bacterial communities that reside within the midgut of tsetse flies collected at geographically distinct locations in Kenya and Uganda.

RESULTS: Using culture dependent methods, we isolated 34 strains of bacteria from four different tsetse species (G. pallidipes, G. brevipalpis, G. fuscipes and G. fuscipleuris) captured at three distinct locations in Kenya. To increase the depth of this study, we deep sequenced midguts from individual uninfected and trypanosome infected G. pallidipes captured at two distinct locations in Kenya and one in Uganda. We found that tsetse's obligate endosymbiont, Wigglesworthia, was the most abundant bacterium present in the midgut of G. pallidipes, and the density of this bacterium remained largely consistent regardless of whether or not its tsetse host was infected with trypanosomes. These fly populations also housed the commensal symbiont Sodalis, which was found at significantly higher densities in trypanosome infected compared to uninfected flies. Finally, midguts of field-captured G. pallidipes were colonized with distinct, low density communities of environmentally acquired microbes that differed in taxonomic structure depending on parasite infection status and the geographic location from which the flies were collected.

CONCLUSIONS: The results of this study will enhance our understanding of the tripartite relationship between tsetse, its microbiota and trypanosome vector competence. This information may be useful for developing novel disease control strategies or enhancing the efficacy of those already in use.}, } @article {pmid30470177, year = {2018}, author = {Kame-Ngasse, GI and Njiokou, F and Melachio-Tanekou, TT and Farikou, O and Simo, G and Geiger, A}, title = {Prevalence of symbionts and trypanosome infections in tsetse flies of two villages of the "Faro and Déo" division of the Adamawa region of Cameroon.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {159}, pmid = {30470177}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies are vectors of human and animal African trypanosomiasis. In spite of many decades of chemotherapy and vector control, the disease has not been eradicated. Other methods like the transformation of tsetse fly symbionts to render the fly refractory to trypanosome infection are being evaluated. The aim of the present study was to evaluate the association between trypanosome infections and the presence of symbionts in these tsetse species. Tsetse flies were trapped in two villages of the "Faro and Déo" Division of the Adamawa region of Cameroon. In the field, tsetse fly species were identified and their infection by trypanosomes was checked by microscopy. In the laboratory, DNA was extracted from their midguts and the presence of symbionts (Sodalis glossinidius and Wolbachia sp.) and trypanosomes was checked by PCR. Symbionts/trypanosomes association tests were performed.

RESULTS: Three tsetse fly species including Glossina tachinoides (90.1%), Glossina morsitans submorsitans (9.4%) and Glossina fuscipes fuscipes (0.5%) were caught. In all the population we obtained an occurrence rate of 37.2% for Sodalis glossinidius and 67.6% for Wolbachia irrespective to tsetse flies species. S. glossinidius and Wolbachia sp. occurrence rates were respectively 37 and 68% for G. tachinoides and 28.6 and 59.5% for G. m. submorsitans. Between Golde Bourle and Mayo Dagoum significant differences were observed in the prevalence of symbionts. Prevalence of trypanosomes were 34.8% for Glossina tachinoides and 40.5% for Glossina morsitans submorsitans. In G. tachinoides, the trypanosome infection rates were 11, 2.6 and 13.7%, respectively, for T. brucei s.l., T. congolense forest type and T. congolense savannah type. In G. m. submorsitans, these infection rates were 16.7, 9.5 and, 2.4% respectively, for T. brucei s.l., T. congolense forest type and T. congolense savannah type.

CONCLUSIONS: The rate of tsetse fly infection by trypanosomes was low compared to those obtained in HAT foci of south Cameroon, and this rate was not statistically linked to the rate of symbiont occurrence. This study allowed to show for the first time the presence of Wolbachia sp. in the tsetse fly sub-species Glossina morsitans submorsitans and Glossina tachinoides.}, } @article {pmid30470176, year = {2018}, author = {Zaidman-Rémy, A and Vigneron, A and Weiss, BL and Heddi, A}, title = {What can a weevil teach a fly, and reciprocally? Interaction of host immune systems with endosymbionts in Glossina and Sitophilus.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {150}, pmid = {30470176}, issn = {1471-2180}, support = {R01 AI051584/AI/NIAID NIH HHS/United States ; }, abstract = {The tsetse fly (Glossina genus) is the main vector of African trypanosomes, which are protozoan parasites that cause human and animal African trypanosomiases in Sub-Saharan Africa. In the frame of the IAEA/FAO program 'Enhancing Vector Refractoriness to Trypanosome Infection', in addition to the tsetse, the cereal weevil Sitophilus has been introduced as a comparative system with regards to immune interactions with endosymbionts. The cereal weevil is an agricultural pest that destroys a significant proportion of cereal stocks worldwide. Tsetse flies are associated with three symbiotic bacteria, the multifunctional obligate Wigglesworthia glossinidia, the facultative commensal Sodalis glossinidius and the parasitic Wolbachia. Cereal weevils house an obligatory nutritional symbiosis with the bacterium Sodalis pierantonius, and occasionally Wolbachia. Studying insect host-symbiont interactions is highly relevant both for understanding the evolution of symbiosis and for envisioning novel pest control strategies. In both insects, the long co-evolution between host and endosymbiont has led to a stringent integration of the host-bacteria partnership. These associations were facilitated by the development of specialized host traits, including symbiont-housing cells called bacteriocytes and specific immune features that enable both tolerance and control of the bacteria. In this review, we compare the tsetse and weevil model systems and compile the latest research findings regarding their biological and ecological similarities, how the immune system controls endosymbiont load and location, and how host-symbiont interactions impact developmental features including cuticle synthesis and immune system maturation. We focus mainly on the interactions between the obligate symbionts and their host's immune systems, a central theme in both model systems. Finally, we highlight how parallel studies on cereal weevils and tsetse flies led to mutual discoveries and stimulated research on each model, creating a pivotal example of scientific improvement through comparison between relatively distant models.}, } @article {pmid30470175, year = {2018}, author = {Wamiti, LG and Khamis, FM and Abd-Alla, AMM and Ombura, FLO and Akutse, KS and Subramanian, S and Odiwuor, SO and Ochieng, SJ and Ekesi, S and Maniania, NK}, title = {Metarhizium anisopliae infection reduces Trypanosoma congolense reproduction in Glossina fuscipes fuscipes and its ability to acquire or transmit the parasite.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {142}, pmid = {30470175}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse fly-borne trypanosomiasis remains a significant problem in Africa despite years of interventions and research. The need for new strategies to control and possibly eliminate trypanosomiasis cannot be over-emphasized. Entomopathogenic fungi (EPF) infect their hosts through the cuticle and proliferate within the body of the host causing death in about 3-14 days depending on the concentration. During the infection process, EPF can reduce blood feeding abilities in hematophagous arthropods such as mosquitoes, tsetse flies and ticks, which may subsequently impact the development and transmission of parasites. Here, we report on the effects of infection of tsetse fly (Glossina fuscipes fuscipes) by the EPF, Metarhizium anisopliae ICIPE 30 wild-type strain (WT) and green fluorescent protein-transformed strain (GZP-1) on the ability of the flies to harbor and transmit the parasite, Trypanosoma congolense.

RESULTS: Teneral flies were fed T. congolense-infected blood for 2 h and then infected using velvet carpet fabric impregnated with conidia covered inside a cylindrical plastic tube for 12 h. Control flies were fed with T. congolense-infected blood but not exposed to the fungal treatment via the carpet fabric inside a cylindrical plastic tube. Insects were dissected at 2, 3, 5 and 7 days post-fungal exposure and the density of parasites quantified. Parasite load decreased from 8.7 × 107 at day 2 to between 8.3 × 104 and 1.3 × 105 T. congolense ml- 1 at day 3 post-fungal exposure in fungus-treated (WT and GZP-1) fly groups. When T. congolense-infected flies were exposed to either fungal strain, they did not transmit the parasite to mice whereas control treatment flies remained capable of parasite transmission. Furthermore, M. anisopliae-inoculated flies which fed on T. congolense-infected mice were not able to acquire the parasites at 4 days post-fungal exposure while parasite acquisition was observed in the control treatment during the same period.

CONCLUSIONS: Infection of the vector G. f. fuscipes by the entomopathogenic fungus M. anisopliae negatively affected the multiplication of the parasite T. congolense in the fly and reduced the vectorial capacity to acquire or transmit the parasite.}, } @article {pmid30470174, year = {2018}, author = {Song, Y and Shin, J and Jin, S and Lee, JK and Kim, DR and Kim, SC and Cho, S and Cho, BK}, title = {Genome-scale analysis of syngas fermenting acetogenic bacteria reveals the translational regulation for its autotrophic growth.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {837}, pmid = {30470174}, issn = {1471-2164}, support = {2011-0031957//National Research Foundation of Korea/ ; 2017R1A2B3011676//National Research Foundation of Korea/ ; 2012M3A6A8054889//National Research Foundation of Korea/ ; 2018M3D3A1A01055733//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Acetogenic bacteria constitute promising biocatalysts for the conversion of CO2/H2 or synthesis gas (H2/CO/CO2) into biofuels and value-added biochemicals. These microorganisms are naturally capable of autotrophic growth via unique acetogenesis metabolism. Despite their biosynthetic potential for commercial applications, a systemic understanding of the transcriptional and translational regulation of the acetogenesis metabolism remains unclear.

RESULTS: By integrating genome-scale transcriptomic and translatomic data, we explored the regulatory logic of the acetogenesis to convert CO2 into biomass and metabolites in Eubacterium limosum. The results indicate that majority of genes associated with autotrophic growth including the Wood-Ljungdahl pathway, the reduction of electron carriers, the energy conservation system, and gluconeogenesis were transcriptionally upregulated. The translation efficiency of genes in cellular respiration and electron bifurcation was also highly enhanced. In contrast, the transcriptionally abundant genes involved in the carbonyl branch of the Wood-Ljungdahl pathway, as well as the ion-translocating complex and ATP synthase complex in the energy conservation system, showed decreased translation efficiency. The translation efficiencies of genes were regulated by 5'UTR secondary structure under the autotrophic growth condition.

CONCLUSIONS: The results illustrated that the acetogenic bacteria reallocate protein synthesis, focusing more on the translation of genes for the generation of reduced electron carriers via electron bifurcation, rather than on those for carbon metabolism under autotrophic growth.}, } @article {pmid30470172, year = {2018}, author = {Demirbas-Uzel, G and Parker, AG and Vreysen, MJB and Mach, RL and Bouyer, J and Takac, P and Abd-Alla, AMM}, title = {Impact of Glossina pallidipes salivary gland hypertrophy virus (GpSGHV) on a heterologous tsetse fly host, Glossina fuscipes fuscipes.}, journal = {BMC microbiology}, volume = {18}, number = {Suppl 1}, pages = {161}, pmid = {30470172}, issn = {1471-2180}, abstract = {BACKGROUND: Tsetse flies (Diptera: Glossinidae) are the vectors of African trypanosomosis, the causal agent of sleeping sickness in humans and nagana in animals. Glossina fuscipes fuscipes is one of the most important tsetse vectors of sleeping sickness, particularly in Central Africa. Due to the development of resistance of the trypanosomes to the commonly used trypanocidal drugs and the lack of effective vaccines, vector control approaches remain the most effective strategies for sustainable management of those diseases. The Sterile Insect Technique (SIT) is an effective, environment-friendly method for the management of tsetse flies in the context of area-wide integrated pest management programs (AW-IPM). This technique relies on the mass-production of the target insect, its sterilization with ionizing radiation and the release of sterile males in the target area where they will mate with wild females and induce sterility in the native population. It has been shown that Glossina pallidipes salivary gland hypertrophy virus (GpSGHV) infection causes a decrease in fecundity and fertility hampering the maintenance of colonies of the tsetse fly G. pallidipes. This virus has also been detected in different species of tsetse files. In this study, we evaluated the impact of GpSGHV on the performance of a colony of the heterologous host G. f. fuscipes, including the flies' productivity, mortality, survival, flight propensity and mating ability and insemination rates.

RESULTS: Even though GpSGHV infection did not induce SGH symptoms, it significantly reduced all examined parameters, except adult flight propensity and insemination rate.

CONCLUSION: These results emphasize the important role of GpSGHV management strategy in the maintenance of G. f. fuscipes colonies and the urgent need to implement measures to avoid virus infection, to ensure the optimal mass production of this tsetse species for use in AW-IPM programs with an SIT component.}, } @article {pmid30468941, year = {2019}, author = {Maddison, DR and Kanda, K and Boyd, OF and Faille, A and Porch, N and Erwin, TL and Roig-Juñent, S}, title = {Phylogeny of the beetle supertribe Trechitae (Coleoptera: Carabidae): Unexpected clades, isolated lineages, and morphological convergence.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {151-176}, doi = {10.1016/j.ympev.2018.11.006}, pmid = {30468941}, issn = {1095-9513}, abstract = {Using data from two nuclear ribosomal genes and four nuclear protein-coding genes, we infer a well-resolved phylogeny of major lineages of the carabid beetle supertribe Trechitae, based upon a sampling of 259 species. Patrobini is the sister group of Trechitae, but the genus Lissopogonus appears to be outside of the Patrobini + Trechitae clade. We find that four enigmatic trechite genera from the Southern Hemisphere, Bembidarenas, Argentinatachoides, Andinodontis, and Tasmanitachoides, form a clade that is the sister group of Trechini; we describe this clade as a new tribe, Bembidarenini. Bembidarenini + Trechini form the sister group of remaining trechites. Within Trechini, subtribe Trechodina is not monophyletic, as three trechodine genera from Australia (Trechobembix, Paratrechodes, Cyphotrechodes) are the sister group of subtribe Trechina. Trechini appears to have originated in the continents of the Southern Hemisphere, with almost all Northern Hemisphere lineages representing a single radiation within the subtribe Trechina. We present moderate evidence that the geographically and phylogenetically isolated genera Sinozolus (six species in the mountains of China), Chaltenia (one species in Argentina and Chile), and Phrypeus (one species in western North America) also form a clade, the tribe Sinozolini. The traditionally recognized tribe Bembidiini sens. lat., diagnosed by the presence of a subulate terminal palpomere, is shown to be polyphyletic; subulate palpomeres have arisen five times within Trechitae. Anillini is monophyletic, and the sister group of Tachyini + Pogonini + Bembidiini + Zolini + Sinozolini; within anillines, we confirm earlier results indicating the eyed New Zealand genus Nesamblyops as the sister to the rest. Sampled New World Pogonini are monophyletic, rendering the genus Pogonus non-monophyletic. Tachyina and Xystosomina are sister groups. Within Xystosomina, the New World members are monophyletic, and are sister to an Australia-New Zealand clade. The latter consists of the genus Philipis as well as taxa not previously recognized as xystosomines: Kiwitachys, the "Tachys" ectromioides group, and "Tachys" mulwalensis. Within Tachyina, the subgenus Elaphropus is not closely related to other subgenera previously placed in the genus Elaphropus; we move the other subgenera into the genus Tachyura. Tachyina with a bifoveate mentum do not form a clade; in fact, a bifoveate mentum is found in Xystosomina, Sinozolini, Trechini, Trechitae and its sister group, Patrobini. Extensive homoplasy in the morphological characters previously used as key indicators of relationship is supported by our results: in addition to multiple origins of subulate palpomeres and bifoveate menta, a concave protibial notch has arisen independently in Anillina, Xystosomina, and Tachyina. Phylogenetically and geographically isolated, species-poor lineages in Trechini, Bembidarenini, and Sinozolini may be relicts of more widespread faunas; many of these are found today on gravel or sand shores of creeks and rivers, which may be an ancestral habitat for portions of Trechitae. In addition to the description of Bembidarenini, we present a diagnosis of the newly delimited Sinozolini, and keys to the tribes of Trechitae.}, } @article {pmid30468940, year = {2019}, author = {Nigenda-Morales, SF and Gompper, ME and Valenzuela-Galván, D and Lay, AR and Kapheim, KM and Hass, C and Booth-Binczik, SD and Binczik, GA and Hirsch, BT and McColgin, M and Koprowski, JL and McFadden, K and Wayne, RK and Koepfli, KP}, title = {Phylogeographic and diversification patterns of the white-nosed coati (Nasua narica): Evidence for south-to-north colonization of North America.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {149-163}, doi = {10.1016/j.ympev.2018.11.011}, pmid = {30468940}, issn = {1095-9513}, abstract = {White-nosed coatis (Nasua narica) are widely distributed throughout North, Central, and South America, but the patterns of temporal and spatial diversification that have contributed to this distribution are unknown. In addition, the biogeographic history of procyonid species in the Americas remains contentious. Using sequences from three mitochondrial loci (Cytochrome b, NAHD5 and 16S rRNA; 2201 bp) and genotypes from 11 microsatellite loci, we analyzed genetic diversity to determine phylogeographic patterns, genetic structure, divergence times, and gene flow among Nasua narica populations throughout the majority of the species' range. We also estimated the ancestral geographic range of N. narica and other procyonid species. We found a high degree of genetic structure and divergence among populations that conform to five evolutionarily significant units. The most southerly distributed population (Panama) branched off much earlier (∼3.8 million years ago) than the northern populations (<1.2 million years ago). Estimated gene flow among populations was low and mostly northwards and westwards. The phylogeographic patterns within N. narica are associated with geographic barriers and habitat shifts likely caused by Pliocene-Pleistocene climate oscillations. Significantly, our findings suggest the dispersal of N. narica was south-to-north beginning in the Pliocene, not in the opposite direction during the Pleistocene as suggested by the fossil record, and that the most recent common ancestor for coati species was most likely distributed in South or Central America six million years ago. Our study implies the possibility that the diversification of Nasua species, and other extant procyonid lineages, may have occurred in South America.}, } @article {pmid30468939, year = {2019}, author = {Weber, AA and Stöhr, S and Chenuil, A}, title = {Species delimitation in the presence of strong incomplete lineage sorting and hybridization: Lessons from Ophioderma (Ophiuroidea: Echinodermata).}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {138-148}, doi = {10.1016/j.ympev.2018.11.014}, pmid = {30468939}, issn = {1095-9513}, abstract = {Accurate species delimitation is essential to properly assess biodiversity, but also for management and conservation purposes. Yet, it is not always trivial to accurately define species boundaries in closely related species due to incomplete lineage sorting. Additional difficulties may be caused by hybridization, now evidenced as a frequent phenomenon. The brittle star cryptic species complex Ophioderma longicauda encompasses six mitochondrial lineages, including broadcast spawners and internal brooders, yet the actual species boundaries are unknown. Here, we combined three methods to delimit species in the Ophioderma longicauda complex and to infer its divergence history: (i) unsupervised species discovery based on multilocus genotypes; (ii) divergence time estimation using the multi-species coalescent; (iii) divergence scenario testing (including gene flow) using Approximate Bayesian Computation (ABC) methods. 30 sequence markers (transcriptome-based, mitochondrial or non-coding) for 89 O. longicauda and outgroup individuals were used. First, multivariate analyses revealed six genetic clusters, which globally corresponded to the mitochondrial lineages, yet with many exceptions, suggesting ancient hybridization events and challenging traditional mitochondrial barcoding approaches. Second, multi-species coalescent-based analyses confirmed the occurrence of six species and provided divergence time estimates, but the sole use of this method failed to accurately delimit species, highlighting the power of multilocus genotype clustering to delimit recently diverged species. Finally, Approximate Bayesian Computation showed that the most likely scenario involves hybridization between brooders and broadcasters. Our study shows that despite strong incomplete lineage sorting and past hybridization, accurate species delimitation in Ophioderma was possible using a combination of complementary methods. We propose that these methods, especially multilocus genotype clustering, may be useful to resolve other complex speciation histories.}, } @article {pmid30468764, year = {2018}, author = {Gustave, W and Yuan, ZF and Sekar, R and Toppin, V and Liu, JY and Ren, YX and Zhang, J and Chen, Z}, title = {Relic DNA does not obscure the microbial community of paddy soil microbial fuel cells.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.11.002}, pmid = {30468764}, issn = {1769-7123}, abstract = {Soil Microbial Fuel Cells (MFCs) are devices that can generate electricity by using the flooded soil's anode respiring microbial consortium. When the MFC starts to work, the microbial community in the anode vicinity rapidly changes. This shift in the microbial community results in many dead cells that may release their DNA (relic DNA) and obscure culture independent estimates of microbial community composition. Although relic DNA is expected to increase in MFCs, the effect of relic DNA has not been investigated in the soil MFCs system. In this study the effect of the MFCs on the soil microbial community composition within the soil profile and the influence of relic DNA were investigated. Microbial community analysis revealed that the MFCs deployment significantly influenced the community composition within the soil profile. The phylum Proteobacteria (34.4% vs 23.6%) and the class Deltaproteobacteria (16.8% vs 5.9%) significantly increased in the MFCs compared to the control, while the phylum Firmicutes (24.0% vs 28.7%) and the class Sphingobacteria (5.3% vs 7.0%) were more abundant in the control. Furthermore, the archaeal phyla Euryarchaeota (40.7% vs 52.3%) and Bathyarchaeota (10.1% vs 17.3%) were significantly lower in the MFCs, whereas the phylum Woesearchaeota (DHVEG6) (24.4% vs 19.4%) was slightly enhanced. Moreover, the results showed that relic DNA can affect the relative abundance of Geobacter and Candidatus Methanoperedens, however, it has no significant effects on the microbial community structure. These results indicate that MFCs can influence the soil microbial community profile, nevertheless the relic DNA generated has minimum effect on the culture independent estimates of microbial community composition.}, } @article {pmid30468763, year = {2018}, author = {Iyer, R and Moussa, SH and Tommasi, R and Miller, AA}, title = {Role of the Klebsiella pneumoniae TolC porin in antibiotic efflux.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.11.003}, pmid = {30468763}, issn = {1769-7123}, abstract = {The major Gram-negative gated efflux channel TolC has been extensively characterized in Escherichia coli but there is minimal information about Klebsiella pneumoniae TolC. Using an arabinose-inducible plasmid-based expression system, we show that the K. pneumoniae TolC complements the efflux defect in an E. coli K-12 ΔtolC strain, restoring wild-type levels of resistance towards most antibiotics suggesting that it can interact with the E. coli AcrB efflux pump. We characterize the efflux properties of K. pneumoniae TolC using an orthogonal whole cell-based assay and quantify the extrusion of environment-sensitive fluorescent probes and contrast the findings with the E. coli ortholog.}, } @article {pmid30468713, year = {2019}, author = {Zandvakili, A and Uhl, JD and Campbell, I and Salomone, J and Song, YC and Gebelein, B}, title = {The cis-regulatory logic underlying abdominal Hox-mediated repression versus activation of regulatory elements in Drosophila.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {226-236}, doi = {10.1016/j.ydbio.2018.11.006}, pmid = {30468713}, issn = {1095-564X}, support = {R01 GM079428/GM/NIGMS NIH HHS/United States ; T32 GM063483/GM/NIGMS NIH HHS/United States ; }, abstract = {During development diverse transcription factor inputs are integrated by cis-regulatory modules (CRMs) to yield cell-specific gene expression. Defining how CRMs recruit the appropriate combinations of factors to either activate or repress gene expression remains a challenge. In this study, we compare and contrast the ability of two CRMs within the Drosophila embryo to recruit functional Hox transcription factor complexes. The DCRE CRM recruits Ultrabithorax (Ubx) and Abdominal-A (Abd-A) Hox complexes that include the Extradenticle (Exd) and Homothorax (Hth) transcription factors to repress the Distal-less leg selector gene, whereas the RhoA CRM selectively recruits Abd-A/Exd/Hth complexes to activate rhomboid and stimulate Epidermal Growth Factor secretion in sensory cell precursors. By swapping binding sites between these elements, we found that the RhoA Exd/Hth/Hox site configuration that mediates Abd-A specific activation can convey transcriptional repression by both Ubx and Abd-A when placed into the DCRE. We further show that the orientation and spacing of Hox sites relative to additional binding sites within the RhoA and DCRE is critical to mediate cell- and segment-specific output. These results indicate that the configuration of Exd, Hth, and Hox site within RhoA is neither Abd-A specific nor activation specific. Instead Hox specific output is largely dependent upon the presence of appropriately spaced and oriented binding sites for additional TF inputs. Taken together, these studies provide insight into the cis-regulatory logic used to generate cell-specific outputs via recruiting Hox transcription factor complexes.}, } @article {pmid30468307, year = {2018}, author = {Alibardi, L}, title = {Perspective: Appendage regeneration in amphibians and some reptiles derived from specific evolutionary histories.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {8}, pages = {396-405}, doi = {10.1002/jez.b.22835}, pmid = {30468307}, issn = {1552-5015}, abstract = {Some hypotheses on the evolution of regeneration in amphibians and reptiles are presented. Amphibian regeneration is derived from metamorphosis present in sarcopterygian fish and amphibians of the Devonian-Carboniferous. The genetic ability to rebuild organs during metamorphosis was maintained in form of "regeneration" in urodele and anuran tadpoles. Amphibian regeneration may be a consequence of the transition from an aquatic to a terrestrial environment through the evolution of a developmental program for the tadpole stage and replacements of adult organs controlled by the endocrine and immune system. Following metamorphosis, the regeneration program for terrestrial anurans and amniotes was lost or modified, whereas the immune system involved in self-integrity and microbial protection became in charge of regeneration that was replaced by scarring. Among amniotes only lizards regenerate an organ as large and complex as the tail. It is hypothesized that in Permian captorhinids and in Triassic lizards (eosuchians) a regenerative blastema evolved in relation to autotomy, a unique phenomenon present in these reptiles that enhanced survival against the larger predators of the Permian-Mesozoic. Appendage regeneration in amphibians and lizards occurs after the migration of activated mesenchymal and epidermal cells in the wounded areas to form soft and hyaluronate-rich blastemas. Autotomy and production of high hyaluronate levels allows high hydration and immunosuppression, favoring regeneration. It is suggested that a way for regenerative medicine to induce limb regeneration in humans is to develop medical procedures to recreate soft blastemas that can grow, a long and difficult process because it counteracts mammalian evolution toward scarring.}, } @article {pmid30467974, year = {2019}, author = {Huber, JA and Preston, C}, title = {Take to the high seas: microbiology labs below the ocean surface.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {23-25}, doi = {10.1111/1758-2229.12714}, pmid = {30467974}, issn = {1758-2229}, support = {//Gordon and Betty Moore Foundation/ ; //NASA/ ; //NSF/ ; //NOPP/ ; //Keck Foundation/ ; //David and Lucille Packard Foundation/ ; }, } @article {pmid30467946, year = {2018}, author = {Gómez, JM and Schupp, EW and Jordano, P}, title = {Synzoochory: the ecological and evolutionary relevance of a dual interaction.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12481}, pmid = {30467946}, issn = {1469-185X}, support = {CGL2017-82847-P//Spanish Ministry of Science, Innovation, and Universities (AEI)/ ; //Utah Agricultural Experiment Station (UAES), Utah State University/ ; 418RT0555//CYTED/ ; }, } @article {pmid30467934, year = {2018}, author = {Barui, A and Datta, P}, title = {Biophysical factors in the regulation of asymmetric division of stem cells.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12479}, pmid = {30467934}, issn = {1469-185X}, abstract = {Stem cells are a promising cell source for regenerative medicine due to their characteristics of self-renewal and differentiation. The intricate balance between these two cell fates is maintained by precisely controlled symmetric and asymmetric cell divisions. Asymmetric division has a fundamental importance in maintaining tissue homeostasis and in the development of multi-cellular organisms. For example, during development, asymmetric cell divisions are responsible for the formation of the body axis. Mechanistically, mitotic spindle dynamics determine the assembly and separation of chromosomes and regulate the orientation of cell division. Interestingly, symmetric and asymmetric cell division is not mutually exclusive and a range of factors are involved in such cell-fate decisions, the measurement of which can provide efficient and reliable information on the regenerative potential of a cell. The balance between self-renewal and differentiation in stem cells is controlled by various biophysical and biochemical cues. Although the role of biochemical factors in asymmetric stem cell division has been widely studied, the effect of biophysical cues in stem-cell self-renewal is not comprehensively understood. Herein, we review the biological relevance of stem-cell asymmetric division to regenerative medicine and discuss the influences of various intrinsic and extrinsic biophysical cues in stem-cell self-renewal. This review particularly aims to inform the clinical translation of efforts to control the self-renewal ability of stem cells through the tuning of various biophysical cues.}, } @article {pmid30467930, year = {2018}, author = {Reid, AJ and Carlson, AK and Creed, IF and Eliason, EJ and Gell, PA and Johnson, PTJ and Kidd, KA and MacCormack, TJ and Olden, JD and Ormerod, SJ and Smol, JP and Taylor, WW and Tockner, K and Vermaire, JC and Dudgeon, D and Cooke, SJ}, title = {Emerging threats and persistent conservation challenges for freshwater biodiversity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12480}, pmid = {30467930}, issn = {1469-185X}, support = {//United States Department of Agriculture/ ; //National Institute of Food and Agriculture/ ; //National Science Foundation/ ; //Natural Environment Research Council/ ; //Canada Research Chairs/ ; //David and Lucile Packard Foundation/ ; }, abstract = {In the 12 years since Dudgeon et al. (2006) reviewed major pressures on freshwater ecosystems, the biodiversity crisis in the world's lakes, reservoirs, rivers, streams and wetlands has deepened. While lakes, reservoirs and rivers cover only 2.3% of the Earth's surface, these ecosystems host at least 9.5% of the Earth's described animal species. Furthermore, using the World Wide Fund for Nature's Living Planet Index, freshwater population declines (83% between 1970 and 2014) continue to outpace contemporaneous declines in marine or terrestrial systems. The Anthropocene has brought multiple new and varied threats that disproportionately impact freshwater systems. We document 12 emerging threats to freshwater biodiversity that are either entirely new since 2006 or have since intensified: (i) changing climates; (ii) e-commerce and invasions; (iii) infectious diseases; (iv) harmful algal blooms; (v) expanding hydropower; (vi) emerging contaminants; (vii) engineered nanomaterials; (viii) microplastic pollution; (ix) light and noise; (x) freshwater salinisation; (xi) declining calcium; and (xii) cumulative stressors. Effects are evidenced for amphibians, fishes, invertebrates, microbes, plants, turtles and waterbirds, with potential for ecosystem-level changes through bottom-up and top-down processes. In our highly uncertain future, the net effects of these threats raise serious concerns for freshwater ecosystems. However, we also highlight opportunities for conservation gains as a result of novel management tools (e.g. environmental flows, environmental DNA) and specific conservation-oriented actions (e.g. dam removal, habitat protection policies, managed relocation of species) that have been met with varying levels of success. Moving forward, we advocate hybrid approaches that manage fresh waters as crucial ecosystems for human life support as well as essential hotspots of biodiversity and ecological function. Efforts to reverse global trends in freshwater degradation now depend on bridging an immense gap between the aspirations of conservation biologists and the accelerating rate of species endangerment.}, } @article {pmid30467416, year = {2018}, author = {}, title = {Challenging climate.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1825}, doi = {10.1038/s41559-018-0748-3}, pmid = {30467416}, issn = {2397-334X}, } @article {pmid30467415, year = {2018}, author = {Bos, KI}, title = {TB's Chinese travels.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1842-1843}, doi = {10.1038/s41559-018-0732-y}, pmid = {30467415}, issn = {2397-334X}, } @article {pmid30467414, year = {2018}, author = {Furey, NB and Armstrong, JB and Beauchamp, DA and Hinch, SG}, title = {Migratory coupling between predators and prey.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1846-1853}, doi = {10.1038/s41559-018-0711-3}, pmid = {30467414}, issn = {2397-334X}, abstract = {Animal migrations act to couple ecosystems and are undertaken by some of the world's most endangered taxa. Predators often exploit migrant prey, but the movements taken by these consumers are rarely studied or understood. We define such movements, where migrant prey induce large-scale movements of predators, as migratory coupling. Migratory coupling can have ecological consequences for the participating prey, predators and the communities they traverse across the landscape. We review examples of migratory coupling in the literature and provide hypotheses regarding conditions favourable for their occurrence. We also provide a framework for interactions induced by migratory coupling and demonstrate their potential community-level impacts by examining other forms of spatial shifts in predators. Migratory coupling integrates the fields of landscape, movement, food web and community ecologies, and represents an understudied frontier in ecology.}, } @article {pmid30467180, year = {2018}, author = {Wang, L and Fu, TM and Zhou, Y and Xia, S and Greka, A and Wu, H}, title = {Structures and gating mechanism of human TRPM2.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {}, doi = {10.1126/science.aav4809}, pmid = {30467180}, issn = {1095-9203}, support = {P41 GM103310/GM/NIGMS NIH HHS/United States ; R01 DK095045/DK/NIDDK NIH HHS/United States ; R01 DK099465/DK/NIDDK NIH HHS/United States ; R01 DK103658/DK/NIDDK NIH HHS/United States ; }, abstract = {Transient receptor potential (TRP) melastatin 2 (TRPM2) is a cation channel associated with numerous diseases. It has a C-terminal NUDT9 homology (NUDT9H) domain responsible for binding adenosine diphosphate (ADP)-ribose (ADPR), and both ADPR and calcium (Ca2+) are required for TRPM2 activation. Here we report cryo-electron microscopy structures of human TRPM2 alone, with ADPR, and with ADPR and Ca2+ NUDT9H forms both intra- and intersubunit interactions with the N-terminal TRPM homology region (MHR1/2/3) in the apo state but undergoes conformational changes upon ADPR binding, resulting in rotation of MHR1/2 and disruption of the intersubunit interaction. The binding of Ca2+ further engages transmembrane helices and the conserved TRP helix to cause conformational changes at the MHR arm and the lower gating pore to potentiate channel opening. These findings explain the molecular mechanism of concerted TRPM2 gating by ADPR and Ca2+ and provide insights into the gating mechanism of other TRP channels.}, } @article {pmid30467179, year = {2019}, author = {Sulej, T and Niedźwiedzki, G}, title = {An elephant-sized Late Triassic synapsid with erect limbs.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6422}, pages = {78-80}, doi = {10.1126/science.aal4853}, pmid = {30467179}, issn = {1095-9203}, abstract = {Here, we describe the dicynodont Lisowicia bojani, from the Late Triassic of Poland, a gigantic synapsid with seemingly upright subcursorial limbs that reached an estimated length of more than 4.5 meters, height of 2.6 meters, and body mass of 9 tons. Lisowicia is the youngest undisputed dicynodont and the largest nondinosaurian terrestrial tetrapod from the Triassic. The lack of lines of arrested growth and the highly remodeled cortex of its limb bones suggest permanently rapid growth and recalls that of dinosaurs and mammals. The discovery of Lisowicia overturns the established picture of the Triassic megaherbivore radiation as a phenomenon restricted to dinosaurs and shows that stem-group mammals were capable of reaching body sizes that were not attained again in mammalian evolution until the latest Eocene.}, } @article {pmid30467178, year = {2019}, author = {Akichika, S and Hirano, S and Shichino, Y and Suzuki, T and Nishimasu, H and Ishitani, R and Sugita, A and Hirose, Y and Iwasaki, S and Nureki, O and Suzuki, T}, title = {Cap-specific terminal N6-methylation of RNA by an RNA polymerase II-associated methyltransferase.}, journal = {Science (New York, N.Y.)}, volume = {363}, number = {6423}, pages = {}, doi = {10.1126/science.aav0080}, pmid = {30467178}, issn = {1095-9203}, abstract = {N6-methyladenosine (m6A), a major modification of messenger RNAs (mRNAs), plays critical roles in RNA metabolism and function. In addition to the internal m6A, N6, 2'-O-dimethyladenosine (m6Am) is present at the transcription start nucleotide of capped mRNAs in vertebrates. However, its biogenesis and functional role remain elusive. Using a reverse genetics approach, we identified PCIF1, a factor that interacts with the serine-5-phosphorylated carboxyl-terminal domain of RNA polymerase II, as a cap-specific adenosine methyltransferase (CAPAM) responsible for N6-methylation of m6Am. The crystal structure of CAPAM in complex with substrates revealed the molecular basis of cap-specific m6A formation. A transcriptome-wide analysis revealed that N6-methylation of m6Am promotes the translation of capped mRNAs. Thus, a cap-specific m6A writer promotes translation of mRNAs starting from m6Am.}, } @article {pmid30467172, year = {2018}, author = {Coelho, CH}, title = {Finding my inner Wonder Woman.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {966}, doi = {10.1126/science.362.6417.966}, pmid = {30467172}, issn = {1095-9203}, } @article {pmid30467171, year = {2018}, author = {Rühl, S and Shkarina, K and Demarco, B and Heilig, R and Santos, JC and Broz, P}, title = {ESCRT-dependent membrane repair negatively regulates pyroptosis downstream of GSDMD activation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {956-960}, doi = {10.1126/science.aar7607}, pmid = {30467171}, issn = {1095-9203}, abstract = {Pyroptosis is a lytic form of cell death that is induced by inflammatory caspases upon activation of the canonical or noncanonical inflammasome pathways. These caspases cleave gasdermin D (GSDMD) to generate an N-terminal GSDMD fragment, which executes pyroptosis by forming membrane pores. We found that calcium influx through GSDMD pores serves as a signal for cells to initiate membrane repair by recruiting the endosomal sorting complexes required for transport (ESCRT) machinery to damaged membrane areas, such as the plasma membrane. Inhibition of the ESCRT-III machinery strongly enhances pyroptosis and interleukin-1β release in both human and murine cells after canonical or noncanonical inflammasome activation. These results not only attribute an anti-inflammatory role to membrane repair by the ESCRT-III system but also provide insight into general cellular survival mechanisms during pyroptosis.}, } @article {pmid30467170, year = {2018}, author = {Lebreton, G and Géminard, C and Lapraz, F and Pyrpassopoulos, S and Cerezo, D and Spéder, P and Ostap, EM and Noselli, S}, title = {Molecular to organismal chirality is induced by the conserved myosin 1D.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {949-952}, doi = {10.1126/science.aat8642}, pmid = {30467170}, issn = {1095-9203}, support = {R37 GM057247/GM/NIGMS NIH HHS/United States ; }, abstract = {The emergence of asymmetry from an initially symmetrical state is a universal transition in nature. Living organisms show asymmetries at the molecular, cellular, tissular, and organismal level. However, whether and how multilevel asymmetries are related remains unclear. In this study, we show that Drosophila myosin 1D (Myo1D) and myosin 1C (Myo1C) are sufficient to generate de novo directional twisting of cells, single organs, or the whole body in opposite directions. Directionality lies in the myosins' motor domain and is swappable between Myo1D and Myo1C. In addition, Myo1D drives gliding of actin filaments in circular, counterclockwise paths in vitro. Altogether, our results reveal the molecular motor Myo1D as a chiral determinant that is sufficient to break symmetry at all biological scales through chiral interaction with the actin cytoskeleton.}, } @article {pmid30467169, year = {2018}, author = {Wang, C and Chen, X and Lee, H and Deshmukh, SS and Yoganarasimha, D and Savelli, F and Knierim, JJ}, title = {Egocentric coding of external items in the lateral entorhinal cortex.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {945-949}, pmid = {30467169}, issn = {1095-9203}, support = {R01 MH094146/MH/NIMH NIH HHS/United States ; R01 NS039456/NS/NINDS NIH HHS/United States ; }, abstract = {Episodic memory, the conscious recollection of past events, is typically experienced from a first-person (egocentric) perspective. The hippocampus plays an essential role in episodic memory and spatial cognition. Although the allocentric nature of hippocampal spatial coding is well understood, little is known about whether the hippocampus receives egocentric information about external items. We recorded in rats the activity of single neurons from the lateral entorhinal cortex (LEC) and medial entorhinal cortex (MEC), the two major inputs to the hippocampus. Many LEC neurons showed tuning for egocentric bearing of external items, whereas MEC cells tended to represent allocentric bearing. These results demonstrate a fundamental dissociation between the reference frames of LEC and MEC neural representations.}, } @article {pmid30467168, year = {2018}, author = {Stroeymeyt, N and Grasse, AV and Crespi, A and Mersch, DP and Cremer, S and Keller, L}, title = {Social network plasticity decreases disease transmission in a eusocial insect.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {941-945}, doi = {10.1126/science.aat4793}, pmid = {30467168}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Animal social networks are shaped by multiple selection pressures, including the need to ensure efficient communication and functioning while simultaneously limiting disease transmission. Social animals could potentially further reduce epidemic risk by altering their social networks in the presence of pathogens, yet there is currently no evidence for such pathogen-triggered responses. We tested this hypothesis experimentally in the ant Lasius niger using a combination of automated tracking, controlled pathogen exposure, transmission quantification, and temporally explicit simulations. Pathogen exposure induced behavioral changes in both exposed ants and their nestmates, which helped contain the disease by reinforcing key transmission-inhibitory properties of the colony's contact network. This suggests that social network plasticity in response to pathogens is an effective strategy for mitigating the effects of disease in social groups.}, } @article {pmid30467167, year = {2018}, author = {Faith, JT and Rowan, J and Du, A and Koch, PL}, title = {Plio-Pleistocene decline of African megaherbivores: No evidence for ancient hominin impacts.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {938-941}, doi = {10.1126/science.aau2728}, pmid = {30467167}, issn = {1095-9203}, abstract = {It has long been proposed that pre-modern hominin impacts drove extinctions and shaped the evolutionary history of Africa's exceptionally diverse large mammal communities, but this hypothesis has yet to be rigorously tested. We analyzed eastern African herbivore communities spanning the past 7 million years-encompassing the entirety of hominin evolutionary history-to test the hypothesis that top-down impacts of tool-bearing, meat-eating hominins contributed to the demise of megaherbivores prior to the emergence of Homo sapiens We document a steady, long-term decline of megaherbivores beginning ~4.6 million years ago, long before the appearance of hominin species capable of exerting top-down control of large mammal communities and predating evidence for hominin interactions with megaherbivore prey. Expansion of C4 grasslands can account for the loss of megaherbivore diversity.}, } @article {pmid30467166, year = {2018}, author = {Yang, T and Zhao, YL and Tong, Y and Jiao, ZB and Wei, J and Cai, JX and Han, XD and Chen, D and Hu, A and Kai, JJ and Lu, K and Liu, Y and Liu, CT}, title = {Multicomponent intermetallic nanoparticles and superb mechanical behaviors of complex alloys.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {933-937}, doi = {10.1126/science.aas8815}, pmid = {30467166}, issn = {1095-9203}, abstract = {Alloy design based on single-principal-element systems has approached its limit for performance enhancements. A substantial increase in strength up to gigapascal levels typically causes the premature failure of materials with reduced ductility. Here, we report a strategy to break this trade-off by controllably introducing high-density ductile multicomponent intermetallic nanoparticles (MCINPs) in complex alloy systems. Distinct from the intermetallic-induced embrittlement under conventional wisdom, such MCINP-strengthened alloys exhibit superior strengths of 1.5 gigapascals and ductility as high as 50% in tension at ambient temperature. The plastic instability, a major concern for high-strength materials, can be completely eliminated by generating a distinctive multistage work-hardening behavior, resulting from pronounced dislocation activities and deformation-induced microbands. This MCINP strategy offers a paradigm to develop next-generation materials for structural applications.}, } @article {pmid30467165, year = {2018}, author = {Dominguez-Medina, S and Fostner, S and Defoort, M and Sansa, M and Stark, AK and Halim, MA and Vernhes, E and Gely, M and Jourdan, G and Alava, T and Boulanger, P and Masselon, C and Hentz, S}, title = {Neutral mass spectrometry of virus capsids above 100 megadaltons with nanomechanical resonators.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {918-922}, doi = {10.1126/science.aat6457}, pmid = {30467165}, issn = {1095-9203}, abstract = {Measurement of the mass of particles in the mega- to gigadalton range is challenging with conventional mass spectrometry. Although this mass range appears optimal for nanomechanical resonators, nanomechanical mass spectrometers often suffer from prohibitive sample loss, extended analysis time, or inadequate resolution. We report on a system architecture combining nebulization of the analytes from solution, their efficient transfer and focusing without relying on electromagnetic fields, and the mass measurements of individual particles using nanomechanical resonator arrays. This system determined the mass distribution of ~30-megadalton polystyrene nanoparticles with high detection efficiency and effectively performed molecular mass measurements of empty or DNA-filled bacteriophage T5 capsids with masses up to 105 megadaltons using less than 1 picomole of sample and with an instrument resolution above 100.}, } @article {pmid30467164, year = {2018}, author = {Wang, T}, title = {Paring down to the essentials.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {904}, doi = {10.1126/science.aav6872}, pmid = {30467164}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, } @article {pmid30467163, year = {2018}, author = {Wan, R}, title = {A key component of gene expression, revealed.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {904}, doi = {10.1126/science.aav6875}, pmid = {30467163}, issn = {1095-9203}, } @article {pmid30467162, year = {2018}, author = {Savoca, M}, title = {The ecology of an olfactory trap.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {904}, doi = {10.1126/science.aav6873}, pmid = {30467162}, issn = {1095-9203}, } @article {pmid30467161, year = {2018}, author = {Thaiss, CA}, title = {Microbiome dynamics in obesity.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {903-904}, doi = {10.1126/science.aav6870}, pmid = {30467161}, issn = {1095-9203}, } @article {pmid30467160, year = {2018}, author = {Hazel, JW and Clayton, EW and Malin, BA and Slobogin, C}, title = {Is it time for a universal genetic forensic database?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {898-900}, doi = {10.1126/science.aav5475}, pmid = {30467160}, issn = {1095-9203}, support = {RM1 HG009034/HG/NHGRI NIH HHS/United States ; }, } @article {pmid30467159, year = {2018}, author = {Ramakrishnan, V and Henderson, R}, title = {Thomas A. Steitz (1940-2018).}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {897}, doi = {10.1126/science.aav8253}, pmid = {30467159}, issn = {1095-9203}, } @article {pmid30467158, year = {2018}, author = {Yamamoto, R and Wilkinson, AC and Nakauchi, H}, title = {Changing concepts in hematopoietic stem cells.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {895-896}, doi = {10.1126/science.aat7873}, pmid = {30467158}, issn = {1095-9203}, support = {R01 DK116944/DK/NIDDK NIH HHS/United States ; R01 HL147124/HL/NHLBI NIH HHS/United States ; }, } @article {pmid30467157, year = {2018}, author = {Chanock, SJ}, title = {The paradox of mutations and cancer.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {893-894}, doi = {10.1126/science.aav5697}, pmid = {30467157}, issn = {1095-9203}, mesh = {Clone Cells ; Diploidy ; Esophagus ; Humans ; *Mutation ; *Neoplasms ; }, } @article {pmid30467156, year = {2018}, author = {Bobe, R and Carvalho, S}, title = {The decline of Africa's largest mammals.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {892-893}, doi = {10.1126/science.aav6883}, pmid = {30467156}, issn = {1095-9203}, mesh = {Africa ; Animals ; *Hominidae ; *Mammals ; }, } @article {pmid30467155, year = {2018}, author = {Willenborg, S and Eming, SA}, title = {Cellular networks in wound healing.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {891-892}, doi = {10.1126/science.aav5542}, pmid = {30467155}, issn = {1095-9203}, mesh = {Cell Proliferation ; Macrophages ; *Myofibroblasts ; *Wound Healing ; }, } @article {pmid30467154, year = {2018}, author = {Cinner, J}, title = {How behavioral science can help conservation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {889-890}, doi = {10.1126/science.aau6028}, pmid = {30467154}, issn = {1095-9203}, } @article {pmid30467153, year = {2018}, author = {Pietrzak, B and Sharma, V and Wasalathanthri, D and Ellwanger, JH and Sanganyado, E and Buschke, F and Beardsley, FR and Agarwal, D and Jensen, MM and Easun, TL and Lin, H and Zhou, K and Jordan, EJ and Oda, FS and MacKay, H and Coffey, E and Yoho, R and Winter, M}, title = {Nurturing connections to the environment.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {886-888}, doi = {10.1126/science.aav9402}, pmid = {30467153}, issn = {1095-9203}, } @article {pmid30467152, year = {2018}, author = {Sokol, J}, title = {Cracking the Cambrian.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {880-884}, doi = {10.1126/science.362.6417.880}, pmid = {30467152}, issn = {1095-9203}, } @article {pmid30467151, year = {2018}, author = {Vogel, G}, title = {Giant mammal cousin rivaled early dinosaurs.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {879}, doi = {10.1126/science.362.6417.879}, pmid = {30467151}, issn = {1095-9203}, } @article {pmid30467150, year = {2018}, author = {Normile, D}, title = {Asia set to take center stage in Higgs studies.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {878}, doi = {10.1126/science.362.6417.878}, pmid = {30467150}, issn = {1095-9203}, } @article {pmid30467149, year = {2018}, author = {Leslie, M}, title = {Artificial cells gain communication skills.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {877}, doi = {10.1126/science.362.6417.877}, pmid = {30467149}, issn = {1095-9203}, } @article {pmid30467148, year = {2018}, author = {Voosen, P}, title = {NASA to pay private space companies for moon rides.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {875-876}, doi = {10.1126/science.362.6417.875}, pmid = {30467148}, issn = {1095-9203}, } @article {pmid30467147, year = {2018}, author = {Stokstad, E}, title = {Luxe research ship to explore the deep ocean.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {874-875}, doi = {10.1126/science.362.6417.874}, pmid = {30467147}, issn = {1095-9203}, } @article {pmid30467146, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {872-873}, doi = {10.1126/science.362.6417.872}, pmid = {30467146}, issn = {1095-9203}, } @article {pmid30467145, year = {2018}, author = {Zittrain, J}, title = {Fixing the internet.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {871}, doi = {10.1126/science.aaw0798}, pmid = {30467145}, issn = {1095-9203}, } @article {pmid30467144, year = {2018}, author = {Shook, BA and Wasko, RR and Rivera-Gonzalez, GC and Salazar-Gatzimas, E and López-Giráldez, F and Dash, BC and Muñoz-Rojas, AR and Aultman, KD and Zwick, RK and Lei, V and Arbiser, JL and Miller-Jensen, K and Clark, DA and Hsia, HC and Horsley, V}, title = {Myofibroblast proliferation and heterogeneity are supported by macrophages during skin repair.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {}, doi = {10.1126/science.aar2971}, pmid = {30467144}, issn = {1095-9203}, support = {R01 AR060295/AR/NIAMS NIH HHS/United States ; R01 AR069550/AR/NIAMS NIH HHS/United States ; P30 AG021342/AG/NIA NIH HHS/United States ; }, abstract = {During tissue repair, myofibroblasts produce extracellular matrix (ECM) molecules for tissue resilience and strength. Altered ECM deposition can lead to tissue dysfunction and disease. Identification of distinct myofibroblast subsets is necessary to develop treatments for these disorders. We analyzed profibrotic cells during mouse skin wound healing, fibrosis, and aging and identified distinct subpopulations of myofibroblasts, including adipocyte precursors (APs). Multiple mouse models and transplantation assays demonstrate that proliferation of APs but not other myofibroblasts is activated by CD301b-expressing macrophages through insulin-like growth factor 1 and platelet-derived growth factor C. With age, wound bed APs and differential gene expression between myofibroblast subsets are reduced. Our findings identify multiple fibrotic cell populations and suggest that the environment dictates functional myofibroblast heterogeneity, which is driven by fibroblast-immune interactions after wounding.}, } @article {pmid30467143, year = {2018}, author = {Yan, L and Chen, J and Zhu, X and Sun, J and Wu, X and Shen, W and Zhang, W and Tao, Q and Meng, A}, title = {Maternal Huluwa dictates the embryonic body axis through β-catenin in vertebrates.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {}, doi = {10.1126/science.aat1045}, pmid = {30467143}, issn = {1095-9203}, abstract = {The vertebrate body is formed by cell movements and shape change during embryogenesis. It remains undetermined which maternal signals govern the formation of the dorsal organizer and the body axis. We found that maternal depletion of huluwa, a previously unnamed gene, causes loss of the dorsal organizer, the head, and the body axis in zebrafish and Xenopus embryos. Huluwa protein is found on the plasma membrane of blastomeres in the future dorsal region in early zebrafish blastulas. Huluwa has strong dorsalizing and secondary axis-inducing activities, which require β-catenin but can function independent of Wnt ligand/receptor signaling. Mechanistically, Huluwa binds to and promotes the tankyrase-mediated degradation of Axin. Therefore, maternal Huluwa is an essential determinant of the dorsal organizer and body axis in vertebrate embryos.}, } @article {pmid30467142, year = {2018}, author = {Pretty, J}, title = {Intensification for redesigned and sustainable agricultural systems.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {}, doi = {10.1126/science.aav0294}, pmid = {30467142}, issn = {1095-9203}, abstract = {Redesign of agricultural systems is essential to deliver optimum outcomes as ecological and economic conditions change. The combination of agricultural processes in which production is maintained or increased, while environmental outcomes are enhanced, is currently known as sustainable intensification (SI). SI aims to avoid the cultivation of more land, and thus avoid the loss of unfarmed habitats, but also aims to increase overall system performance without net environmental cost. For example, large changes are now beginning to occur to maximize biodiversity by means of integrated pest management, pasture and forage management, the incorporation of trees into agriculture, and irrigation management, and with small and patch systems. SI is central to the Sustainable Development Goals of the United Nations and to wider efforts to improve global food and nutritional security.}, } @article {pmid30466901, year = {2019}, author = {Hampl, V and Čepička, I and Eliáš, M}, title = {Was the Mitochondrion Necessary to Start Eukaryogenesis?.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {96-104}, doi = {10.1016/j.tim.2018.10.005}, pmid = {30466901}, issn = {1878-4380}, abstract = {Arguments based on cell energetics favour the view that a mitochondrion capable of oxidative phosphorylation was a prerequisite for the evolution of other features of the eukaryotic cell, including increased volume, genome size and, eventually, phagotrophy. Contrary to this we argue that: (i) extant amitochondriate eukaryotes possess voluminous phagotrophic cells with large genomes; (ii) picoeukaryotes demonstrate that phagotrophy is feasible at prokaryotic cell sizes; and (iii) the assumption that evolution of complex features requires extra ATP, often mentioned in this context, is unfounded and should not be used in such considerations. We claim that the diversity of cell organisations and functions observed today in eukaryotes gives no reason to postulate that a mitochondrion must have preceded phagocytosis in eukaryogenesis.}, } @article {pmid30466900, year = {2018}, author = {Monteiro, R and Pires, DP and Costa, AR and Azeredo, J}, title = {Phage Therapy: Going Temperate?.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.10.008}, pmid = {30466900}, issn = {1878-4380}, abstract = {Strictly lytic phages have been consensually preferred for phage therapy purposes. In contrast, temperate phages have been avoided due to an inherent capacity to mediate transfer of genes between bacteria by specialized transduction - an event that may increase bacterial virulence, for example, by promoting antibiotic resistance. Now, advances in sequencing technologies and synthetic biology are providing new opportunities to explore the use of temperate phages for therapy against bacterial infections. By doing so we can considerably expand our armamentarium against the escalating threat of antibiotic-resistant bacteria.}, } @article {pmid30466730, year = {2019}, author = {Duester, G}, title = {Knocking Out Enhancers to Enhance Epigenetic Research.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {2}, pages = {89}, doi = {10.1016/j.tig.2018.10.001}, pmid = {30466730}, issn = {0168-9525}, support = {R01 AR067731/AR/NIAMS NIH HHS/United States ; }, } @article {pmid30466729, year = {2019}, author = {Montes, M and Sanford, BL and Comiskey, DF and Chandler, DS}, title = {RNA Splicing and Disease: Animal Models to Therapies.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {68-87}, doi = {10.1016/j.tig.2018.10.002}, pmid = {30466729}, issn = {0168-9525}, support = {R21 NS054690/NS/NINDS NIH HHS/United States ; F31 NS079032/NS/NINDS NIH HHS/United States ; R21 CA195324/CA/NCI NIH HHS/United States ; R21 NS084187/NS/NINDS NIH HHS/United States ; T32 NS077984/NS/NINDS NIH HHS/United States ; }, abstract = {Alternative splicing of pre-mRNA increases genetic diversity, and recent studies estimate that most human multiexon genes are alternatively spliced. If this process is not highly regulated and accurate, it leads to mis-splicing events, which may result in proteins with altered function. A growing body of work has implicated mis-splicing events in a range of diseases, including cancer, neurodegenerative diseases, and muscular dystrophies. Understanding the mechanisms that cause aberrant splicing events and how this leads to disease is vital for designing effective therapeutic strategies. In this review, we focus on advances in therapies targeting splicing, and highlight the animal models developed to recapitulate disease phenotypes as a model for testing these therapies.}, } @article {pmid30466491, year = {2018}, author = {Antwis, RE and Lea, JMD and Unwin, B and Shultz, S}, title = {Gut microbiome composition is associated with spatial structuring and social interactions in semi-feral Welsh Mountain ponies.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {207}, pmid = {30466491}, issn = {2049-2618}, abstract = {BACKGROUND: Microbiome composition is linked to host functional traits including metabolism and immune function. Drivers of microbiome composition are increasingly well-characterised; however, evidence of group-level microbiome convergence is limited and may represent a multi-level trait (i.e. across individuals and groups), whereby heritable phenotypes are influenced by social interactions. Here, we investigate the influence of spatial structuring and social interactions on the gut microbiome composition of Welsh mountain ponies.

RESULTS: We show that semi-feral ponies exhibit variation in microbiome composition according to band (group) membership, in addition to considerable within-individual variation. Spatial structuring was also identified within bands, suggesting that despite communal living, social behaviours still influence microbiome composition. Indeed, we show that specific interactions (i.e. mother-offspring and stallion-mare) lead to more similar microbiomes, further supporting the notion that individuals influence the microbiome composition of one another and ultimately the group. Foals exhibited different microbiome composition to sub-adults and adults, most likely related to differences in diet.

CONCLUSIONS: We provide novel evidence that microbiome composition is structured at multiple levels within populations of social mammals and thus may form a unit on which selection can act. High levels of within-individual variation in microbiome composition, combined with the potential for social interactions to influence microbiome composition, suggest the direction of microbiome selection may be influenced by the individual members present in the group. Although the functional implications of this require further research, these results lend support to the idea that multi-level selection can act on microbiomes.}, } @article {pmid30466490, year = {2018}, author = {Stanford, KR and Ajmo, JM and Bahia, PK and Hadley, SH and Taylor-Clark, TE}, title = {Improving redox sensitivity of roGFP1 by incorporation of selenocysteine at position 147.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {827}, pmid = {30466490}, issn = {1756-0500}, support = {R01 HL119802/HL/NHLBI NIH HHS/United States ; R01HL119802//National Institutes of Health/ ; }, abstract = {OBJECTIVE: Redox-sensitive green fluorescent protein (roGFP) is a genetically-encoded redox-sensitive protein used to detect cellular oxidative stress associated with reactive oxygen species production. Here we replaced the cysteine at position 147 of roGFP1 (variant of roGFP) with selenocysteine in order to increase redox sensitivity of the redox reporter.

RESULTS: Expression of roGFP1 selenoprotein (roGFP1-Se147) in HEK293 cells required the presence of a selenocysteine insertion sequence and was augmented by co-expression with SBP2. roGFP1-Se147 demonstrated a similar excitation and emission spectra to roGFP1. Although expression of roGFP1-Se147 was limited, it was sufficient enough to perform live cell imaging to evaluate sensitivity to oxidation and reduction. roGFP1-Se147 exhibited a 100-fold increase in sensitivity to oxidation with H2O2 in comparison to roGFP1 as well as a 20-fold decrease in the EC50 of H2O2. Furthermore, roGFP1-Se147, unlike roGFP1, was able to detect oxidation caused by the mitochondrial electron transport complex III inhibitor antimycin A. Unfortunately roGFP-Se147 exhibited a diminished dynamic range and photoinstability.}, } @article {pmid30466483, year = {2018}, author = {Martins, C and Varela, A and Leclercq, CC and Núñez, O and Větrovský, T and Renaut, J and Baldrian, P and Silva Pereira, C}, title = {Specialisation events of fungal metacommunities exposed to a persistent organic pollutant are suggestive of augmented pathogenic potential.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {208}, pmid = {30466483}, issn = {2049-2618}, support = {647928//European Research Council/International ; }, abstract = {BACKGROUND: The impacts of man-made chemicals, in particular of persistent organic pollutants, are multifactorial as they may affect the integrity of ecosystems, alter biodiversity and have undesirable effects on many organisms. We have previously demonstrated that the belowground mycobiota of forest soils acts as a buffer against the biocide pollutant pentachlorophenol. However, the trade-offs made by mycobiota to mitigate this pollutant remain cryptic.

RESULTS: Herein, we demonstrate using a culture-dependent approach that exposure to pentachlorophenol led to alterations in the composition and functioning of the metacommunity, many of which were not fully alleviated when most of the biocide was degraded. Proteomic and physiological analyses showed that the carbon and nitrogen metabolisms were particularly affected. This dysregulation is possibly linked to the higher pathogenic potential of the metacommunity following exposure to the biocide, supported by the secretion of proteins related to pathogenicity and reduced susceptibility to a fungicide. Our findings provide additional evidence for the silent risks of environmental pollution, particularly as it may favour the development of pathogenic trade-offs in fungi, which may impose serious threats to animals and plant hosts.}, } @article {pmid30466434, year = {2018}, author = {Petrů, M and Wideman, J and Moore, K and Alcock, F and Palmer, T and Doležal, P}, title = {Evolution of mitochondrial TAT translocases illustrates the loss of bacterial protein transport machines in mitochondria.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {141}, pmid = {30466434}, issn = {1741-7007}, abstract = {BACKGROUND: Bacteria and mitochondria contain translocases that function to transport proteins across or insert proteins into their inner and outer membranes. Extant mitochondria retain some bacterial-derived translocases but have lost others. While BamA and YidC were integrated into general mitochondrial protein transport pathways (as Sam50 and Oxa1), the inner membrane TAT translocase, which uniquely transports folded proteins across the membrane, was retained sporadically across the eukaryote tree.

RESULTS: We have identified mitochondrial TAT machinery in diverse eukaryotic lineages and define three different types of eukaryote-encoded TatABC-derived machineries (TatAC, TatBC and TatC-only). Here, we investigate TatAC and TatC-only machineries, which have not been studied previously. We show that mitochondria-encoded TatAC of the jakobid Andalucia godoyi represent the minimal functional pathway capable of substituting for the Escherichia coli TatABC complex and can transport at least one substrate. However, selected TatC-only machineries, from multiple eukaryotic lineages, were not capable of supporting the translocation of this substrate across the bacterial membrane. Despite the multiple losses of the TatC gene from the mitochondrial genome, the gene was never transferred to the cell nucleus. Although the major constraint preventing nuclear transfer of mitochondrial TatC is likely its high hydrophobicity, we show that in chloroplasts, such transfer of TatC was made possible due to modifications of the first transmembrane domain.

CONCLUSIONS: At its origin, mitochondria inherited three inner membrane translocases Sec, TAT and Oxa1 (YidC) from its bacterial ancestor. Our work shows for the first time that mitochondrial TAT has likely retained its unique function of transporting folded proteins at least in those few eukaryotes with TatA and TatC subunits encoded in the mitochondrial genome. However, mitochondria, in contrast to chloroplasts, abandoned the machinery multiple times in evolution. The overall lower hydrophobicity of the Oxa1 protein was likely the main reason why this translocase was nearly universally retained in mitochondrial biogenesis pathways.}, } @article {pmid30466409, year = {2018}, author = {Thorve, S and Wilson, ML and Lewis, BL and Swarup, S and Vullikanti, AKS and Marathe, MV}, title = {EpiViewer: an epidemiological application for exploring time series data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {449}, pmid = {30466409}, issn = {1471-2105}, support = {HDTRA1-11-D-0016-0001//Defense Threat Reduction Agency/ ; HDTRA1-11-D-0016-0005//Defense Threat Reduction Agency/ ; HDTRA1-17-D-0023//Defense Threat Reduction Agency/ ; HDTRA117F0118//Defense Threat Reduction Agency/ ; }, mesh = {Humans ; Information Dissemination/*methods ; Software/*trends ; }, abstract = {BACKGROUND: Visualization plays an important role in epidemic time series analysis and forecasting. Viewing time series data plotted on a graph can help researchers identify anomalies and unexpected trends that could be overlooked if the data were reviewed in tabular form; these details can influence a researcher's recommended course of action or choice of simulation models. However, there are challenges in reviewing data sets from multiple data sources - data can be aggregated in different ways (e.g., incidence vs. cumulative), measure different criteria (e.g., infection counts, hospitalizations, and deaths), or represent different geographical scales (e.g., nation, HHS Regions, or states), which can make a direct comparison between time series difficult. In the face of an emerging epidemic, the ability to visualize time series from various sources and organizations and to reconcile these datasets based on different criteria could be key in developing accurate forecasts and identifying effective interventions. Many tools have been developed for visualizing temporal data; however, none yet supports all the functionality needed for easy collaborative visualization and analysis of epidemic data.

RESULTS: In this paper, we present EpiViewer, a time series exploration dashboard where users can upload epidemiological time series data from a variety of sources and compare, organize, and track how data evolves as an epidemic progresses. EpiViewer provides an easy-to-use web interface for visualizing temporal datasets either as line charts or bar charts. The application provides enhanced features for visual analysis, such as hierarchical categorization, zooming, and filtering, to enable detailed inspection and comparison of multiple time series on a single canvas. Finally, EpiViewer provides several built-in statistical Epi-features to help users interpret the epidemiological curves.

CONCLUSION: EpiViewer is a single page web application that provides a framework for exploring, comparing, and organizing temporal datasets. It offers a variety of features for convenient filtering and analysis of epicurves based on meta-attribute tagging. EpiViewer also provides a platform for sharing data between groups for better comparison and analysis. Our user study demonstrated that EpiViewer is easy to use and fills a particular niche in the toolspace for visualization and exploration of epidemiological data.}, } @article {pmid30466401, year = {2018}, author = {Zhang, H and Miao, H and Wei, L and Li, C and Duan, Y and Xu, F and Qu, W and Zhao, R and Ju, M and Chang, S}, title = {Identification of a SiCL1 gene controlling leaf curling and capsule indehiscence in sesame via cross-population association mapping and genomic variants screening.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {296}, pmid = {30466401}, issn = {1471-2229}, support = {CARS-14//the earmarked fund for China Agriculture Research System/ ; 31471537//the National Natural Science Foundation of China/ ; 184200510002//the Plan for Scientific Innovation Talent of Henan Province/ ; 151100111200//the Key Project of Science and Technology in Henan Province/ ; 2016-X05//the Importing International Agricultural Sciences and Technology Program/ ; SPPP2016//the Henan Province Specific Professor Position Program/ ; ISTTCPHP2016//the Innovation Scientists and Technicians Troop Construction Projects of Henan Province/ ; DPPIHL2017//the Distinguished Professor Program of Institutions of Higher Learning in Henan Province/ ; }, mesh = {Alleles ; Chromosome Mapping ; Chromosomes, Plant ; Cloning, Molecular ; DNA, Plant ; Fruit/*genetics/growth & development ; *Genes, Plant ; Genes, Recessive ; Genetic Variation ; Inheritance Patterns ; Mutation ; Plant Leaves/*genetics/growth & development ; Plant Proteins/genetics ; Repressor Proteins/genetics ; Sequence Analysis, DNA ; Sesamum/*genetics ; Transcriptome ; }, abstract = {BACKGROUND: Leaf shape can affect plantlet development and seed yield in sesame. The morphological, histological and genetic analyses of a sesame mutant cl1 (cl) with curly leaf and indehiscent capsule traits were performed in this study. In order to clone the cl1 gene for breeding selection, genome re-sequencing of the 130 individuals of cl1 × USA (0)-26 F2 population and a bulked segregation analysis (BSA) pool was carried out. The genome re-sequencing data of the 822 germplasm with normal leaf shape were applied.

RESULTS: For cl1 mutant, the adaxial/abaxial character of the parenchyma cells in the leaf blades is reduced. Results proved that the leaf curling trait is controlled by a recessive gene (Sicl1). Cross- population association of the F2 population of cl1 × USA (0)-26 indicated that the target cl locus was located on the interval C29 between C29_6522236 and C29_6918901 of SiChr. 1. Further regional genome variants screening determined the 6 candidate variants using genomic variants data of 822 natural germplasm and a BSA pool data. Of which, 5 markers C29_6717525, C29_6721553, C29_6721558, C29_6721563, and C29_6721565 existed in the same gene (C29.460). With the aid of the validation in the test F2 population of cl1 × Yuzhi 11 and natural germplasm, the integrated marker SiCLInDel1 (C29: 6721553-6721572) was determined as the target marker, and C29.460 was the target gene SiCL1 in sesame. SiCL1 is a KAN1 homolog with the full length of 6835 bp. In cl1, the 20 nucleic acids (CAGGTAGCTATGTATATGCA) of SiCLInDel1 marker were mutagenized into 6 nucleic acids (TCTTTG). The deletion led to a frameshift mutation and resulted in the earlier translation termination of the CL gene. The Sicl1 allele was shortened to 1829 bp. SiCL1 gene was expressed mainly in the tissues of stem, leaf, bud, capsule and seed.

CONCLUSIONS: SiCL1 encodes a transcription repressor KAN1 protein and controls leaf curling and capsule indehiscence in sesame. The findings provided an example of high-efficient gene cloning in sesame. The SiCL1 gene and the cl1 mutant supply the opportunity to explore the development regulation of leaf and capsule, and would improve the new variety breeding with high harvest mechanization adaption in sesame.}, } @article {pmid30466398, year = {2018}, author = {Burger, F and Angioni, M and Russo, G and Schad, M and Kallarackal, J}, title = {PCRdrive: the largest qPCR assay archive to date and endless potential for lab workflow revitalization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {447}, pmid = {30466398}, issn = {1471-2105}, mesh = {DNA Primers/*genetics ; Real-Time Polymerase Chain Reaction/*methods ; *Workflow ; }, abstract = {BACKGROUND: Primer design is a crucial step in establishing specific and sensitive qPCR assays. Even though numerous tools for primer design exist, the majority of resulting assays still requires extensive testing and optimisation or does not allow for high quality target amplification. We developed a workflow for designing qPCR assays. Unlike other tools, we compute a PCR assay including primer design, concentrations and the optimal PCR program.

RESULTS: Gene expression assays were already generated in a total of 283,226 genes from three species and are continued for all genes of the major model species. The results are available online at https://pcrdrive.com/lab#/assay-database . The workflow involves filtering Primer3-generated primers by considering diverse parameters including specificity, single-nucleotide polymorphisms (SNPs), secondary structure as well as compatibility with standard qPCR assay conditions. The resulting assays consist of transcript-specific primer sequences, a reagents protocol as well as instrument settings which are provided in a web-based tool called PCRdrive. PCRdrive was designed to support PCR users in their PCR-related tasks and is equipped with handy functions, components of an electronic lab notebook (ELN) as well as teamworking opportunities.

CONCLUSION: High quality ready to use qPCR assays for gene expression analysis are provided within the online platform PCRdrive. A built-in primer designer enables easy generation of assays which is not supported by any other tool. The wet lab optimisation of new assays can be transparently documented and shared within the team. PCRdrive also contains an archive of public PCRs which is updated regularly. Users may use the archive to publish their PCR to the community which makes it easy for other researchers worldwide to reproduce and validate the PCR. PCRdrive is a growing network of PCR users, simplifying and streamlining research through its useful existing features and continuous developments from the active development team.}, } @article {pmid30466395, year = {2018}, author = {Queiroux, C and Bonnet, M and Saraoui, T and Delpech, P and Veisseire, P and Rifa, E and Moussard, C and Gagne, G and Delbès, C and Bornes, S}, title = {Dialogue between Staphylococcus aureus SA15 and Lactococcus garvieae strains experiencing oxidative stress.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {193}, pmid = {30466395}, issn = {1471-2180}, support = {Z01 CL001183/CL/CLC NIH HHS/United States ; }, abstract = {BACKGROUND: Staphylococcus aureus is an important foodborne pathogen. Lactococcus garvieae is a lactic acid bacterium found in dairy products; some of its strains are able to inhibit S. aureus growth by producing H2O2. Three strains of L. garvieae from different origins were tested for their ability to inhibit S. aureus SA15 growth. Two conditions were tested, one in which H2O2 was produced (high aeration) and another one in which it was not detected (low aeration). Several S. aureus genes related to stress, H2O2-response and virulence were examined in order to compare their level of expression depending on the inoculated L. garvieae strain. Simultaneous L. garvieae H2O2 metabolism gene expression was followed.

RESULTS: The results showed that under high aeration condition, L. garvieae strains producing H2O2 (N201 and CL-1183) inhibited S. aureus SA15 growth and impaired its ability to deal with hydrogen peroxide by repressing H2O2-degrading genes. L. garvieae strains induced overexpression of S. aureus stress-response genes while cell division genes and virulence genes were repressed. A catalase treatment partially or completely restored the SA15 growth. In addition, the H2O2 non-producing L. garvieae strain (Lg2) did not cause any growth inhibition. The SA15 stress-response genes were down-regulated and cell division genes expression was not affected. Under low aeration condition, while none of the strains tested exhibited H2O2-production, the 3 L. garvieae strains inhibited S. aureus SA15 growth, but to a lesser extent than under high aeration condition.

CONCLUSION: Taken together, these results suggest a L. garvieae strain-specific anti-staphylococcal mechanism and an H2O2 involvement in at least two of the tested L. garvieae strains.}, } @article {pmid30466394, year = {2018}, author = {Saatian, B and Austin, RS and Tian, G and Chen, C and Nguyen, V and Kohalmi, SE and Geelen, D and Cui, Y}, title = {Analysis of a novel mutant allele of GSL8 reveals its key roles in cytokinesis and symplastic trafficking in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {295}, pmid = {30466394}, issn = {1471-2229}, support = {R4019A01//National Science and Engineering Research Council of Canada/ ; }, mesh = {Alleles ; Arabidopsis/genetics/growth & development/*physiology ; Arabidopsis Proteins/genetics/metabolism/*physiology ; *Cytokinesis ; Genetic Pleiotropy ; Glucans/metabolism ; Glucosyltransferases/genetics/metabolism/*physiology ; Membrane Proteins/metabolism ; Mutation ; Plasmodesmata/metabolism ; Seedlings/genetics/growth & development ; }, abstract = {BACKGROUND: Plant cell walls are mainly composed of polysaccharides such as cellulose and callose. Callose exists at a very low level in the cell wall; however, it plays critical roles at different stages of plant development as well as in defence against unfavorable conditions. Callose is accumulated at the cell plate, at plasmodesmata and in male and female gametophytes. Despite the important roles of callose in plants, the mechanisms of its synthesis and regulatory properties are not well understood.

RESULTS: CALLOSE SYNTHASE (CALS) genes, also known as GLUCAN SYNTHASE-LIKE (GSL), comprise a family of 12 members in Arabidopsis thaliana. Here, we describe a new allele of GSL8 (named essp8) that exhibits pleiotropic seedling defects. Reduction of callose deposition at the cell plates and plasmodesmata in essp8 leads to ectopic endomitosis and an increase in the size exclusion limit of plasmodesmata during early seedling development. Movement of two non-cell-autonomous factors, SHORT ROOT and microRNA165/6, both required for root radial patterning during embryonic root development, are dysregulated in the primary root of essp8. This observation provides evidence for a molecular mechanism explaining the gsl8 root phenotype. We demonstrated that GSL8 interacts with PLASMODESMATA-LOCALIZED PROTEIN 5, a β-1,3-glucanase, and GSL10. We propose that they all might be part of a putative callose synthase complex, allowing a concerted regulation of callose deposition at plasmodesmata.

CONCLUSION: Analysis of a novel mutant allele of GSL8 reveals that GSL8 is a key player in early seedling development in Arabidopsis. GSL8 is required for maintaining the basic ploidy level and regulating the symplastic trafficking. Callose deposition at plasmodesmata is highly regulated and occurs through interaction of different components, likely to be incorporated into a callose biosynthesis complex. We are providing new evidence supporting an earlier hypothesis that GSL8 might have regulatory roles apart from its enzymatic function in plasmodesmata regulation.}, } @article {pmid30466390, year = {2018}, author = {Li, Y and Liu, X and Ma, Y and Wang, Y and Zhou, W and Hao, M and Yuan, Z and Liu, J and Xiong, M and Shugart, YY and Wang, J and Jin, L}, title = {knnAUC: an open-source R package for detecting nonlinear dependence between one continuous variable and one binary variable.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {448}, pmid = {30466390}, issn = {1471-2105}, support = {31330038, 31521003//National Natural Science Foundation of China/ ; 2015FY111700//Ministry of Science and Technology/ ; B13016//Ministry of Education of the People's Republic of China/ ; 2014CB541801//National Basic Research Program/ ; 2017SHZDZX01//Shanghai Municipal Science and Technology Major Project/ ; }, mesh = {Cluster Analysis ; Computational Biology/methods ; Humans ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Testing the dependence of two variables is one of the fundamental tasks in statistics. In this work, we developed an open-source R package (knnAUC) for detecting nonlinear dependence between one continuous variable X and one binary dependent variables Y (0 or 1).

RESULTS: We addressed this problem by using knnAUC (k-nearest neighbors AUC test, the R package is available at https://sourceforge.net/projects/knnauc/). In the knnAUC software framework, we first resampled a dataset to get the training and testing dataset according to the sample ratio (from 0 to 1), and then constructed a k-nearest neighbors algorithm classifier to get the yhat estimator (the probability of y = 1) of testy (the true label of testing dataset). Finally, we calculated the AUC (area under the curve of receiver operating characteristic) estimator and tested whether the AUC estimator is greater than 0.5. To evaluate the advantages of knnAUC compared to seven other popular methods, we performed extensive simulations to explore the relationships between eight different methods and compared the false positive rates and statistical power using both simulated and real datasets (Chronic hepatitis B datasets and kidney cancer RNA-seq datasets).

CONCLUSIONS: We concluded that knnAUC is an efficient R package to test non-linear dependence between one continuous variable and one binary dependent variable especially in computational biology area.}, } @article {pmid30466389, year = {2018}, author = {Singh, NK and Bezdan, D and Checinska Sielaff, A and Wheeler, K and Mason, CE and Venkateswaran, K}, title = {Multi-drug resistant Enterobacter bugandensis species isolated from the International Space Station and comparative genomic analyses with human pathogenic strains.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {175}, pmid = {30466389}, issn = {1471-2180}, support = {NNX14AH50G, NNX17AB26G//National Aeronautics and Space Administration/ ; R01ES021006, 1R21AI129851//National Institutes of Health/ ; R01 ES021006/ES/NIEHS NIH HHS/United States ; G-2015-13964//Alfred P. Sloan Foundation/ ; OPP1151054//Bill and Melinda Gates Foundation/ ; R21 AI129851/AI/NIAID NIH HHS/United States ; 19-12829-26//Space Biology/ ; }, abstract = {BACKGROUND: The antimicrobial resistance (AMR) phenotypic properties, multiple drug resistance (MDR) gene profiles, and genes related to potential virulence and pathogenic properties of five Enterobacter bugandensis strains isolated from the International Space Station (ISS) were carried out and compared with genomes of three clinical strains. Whole genome sequences of ISS strains were characterized using the hybrid de novo assembly of Nanopore and Illumina reads. In addition to traditional microbial taxonomic approaches, multilocus sequence typing (MLST) analysis was performed to classify the phylogenetic lineage. Agar diffusion discs assay was performed to test antibiotics susceptibility. The draft genomes after assembly and scaffolding were annotated with the Rapid Annotations using Subsystems Technology and RNAmmer servers for downstream analysis.

RESULTS: Molecular phylogeny and whole genome analysis of the ISS strains with all publicly available Enterobacter genomes revealed that ISS strains were E. bugandensis and similar to the type strain EB-247T and two clinical isolates (153_ECLO and MBRL 1077). Comparative genomic analyses of all eight E. bungandensis strains showed, a total of 4733 genes were associated with carbohydrate metabolism (635 genes), amino acid and derivatives (496 genes), protein metabolism (291 genes), cofactors, vitamins, prosthetic groups, pigments (275 genes), membrane transport (247 genes), and RNA metabolism (239 genes). In addition, 112 genes identified in the ISS strains were involved in virulence, disease, and defense. Genes associated with resistance to antibiotics and toxic compounds, including the MDR tripartite system were also identified in the ISS strains. A multiple antibiotic resistance (MAR) locus or MAR operon encoding MarA, MarB, MarC, and MarR, which regulate more than 60 genes, including upregulation of drug efflux systems that have been reported in Escherichia coli K12, was also observed in the ISS strains.

CONCLUSION: Given the MDR results for these ISS Enterobacter genomes and increased chance of pathogenicity (PathogenFinder algorithm with > 79% probability), these species pose important health considerations for future missions. Thorough genomic characterization of the strains isolated from ISS can help to understand the pathogenic potential, and inform future missions, but analyzing them in in-vivo systems is required to discern the influence of microgravity on their pathogenicity.}, } @article {pmid30466388, year = {2018}, author = {Ansari, A and Zohra, RR and Tarar, OM and Qader, SAU and Aman, A}, title = {Screening, purification and characterization of thermostable, protease resistant Bacteriocin active against methicillin resistant Staphylococcus aureus (MRSA).}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {192}, pmid = {30466388}, issn = {1471-2180}, abstract = {BACKGROUND: The emergence of serious issues of multidrug resistance in the past few years have enforced the use of bacteriocins for combating infections. Threat posed to public health by various multidrug resistant (MDR) organisms can be resolved by discovering new antimicrobial proteins with broad spectrum of inhibition.

RESULTS: In the current study, Bacteriocin (BAC-IB17) produced by Bacillus subtilis KIBGE-IB17 is found to be effective against different strains of methicillin resistant Staphylococcus aureus (MRSA). The approximate molecular mass of BAC-IB17 is 10.7 kDa. This unique bacteriocin is found to be highly thermostable and pH stable in nature. It also showed its stability against various heavy metals, organic solvents, surfactants and proteolytic enzymes. Amino acid profile of BAC-IB17 clearly showed that this protein mainly consists of non-polar and basic amino acids whereas; some acidic amino acids were also detected. Sequence of first 15 amino acid residues obtained from N-terminal sequencing of BAC-IB17 were NKPEALVDYTGVXNS.

CONCLUSIONS: The anti-MRSA property of purified bacteriocin may be used to prevent the spread of MRSA infections. Remarkable features of BAC-IB17 suggests its applications in various pharmaceutical and food industries as it can function under a variety of harsh environmental conditions.}, } @article {pmid30466386, year = {2018}, author = {Demska, K and Filip, E and Skuza, L}, title = {"Expression of genes encoding protein disulfide isomerase (PDI) in cultivars and lines of common wheat with different baking quality of flour".}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {294}, pmid = {30466386}, issn = {1471-2229}, mesh = {Cooking ; *Flour ; Gene Expression ; *Genes, Plant ; Plant Proteins/genetics ; Protein Disulfide-Isomerases/*genetics ; Species Specificity ; Triticum/enzymology/*genetics ; }, abstract = {BACKGROUND: The subject of this research was to investigate the level of expression of genes encoding protein disulfide isomerase (PDI) in cultivars and lines of wheat with different baking value of flour. PDI plays a key role in the formation of disulfide bonds in newly formed proteins. Each of cultivars and lines had a specific set of high molecular weight glutenin subunits (HMW-GS). Based on the presence of individual subunits, the potential baking value is predicted. Sometimes this value is not confirmed during technological analysis. Since there are cases where flour has a better or worse value than expected on the basis of the genotype, the expression of PDI genes was considered as a potential cause for discrepancies mentioned.

RESULTS: Analysis focused on three stages of grain development. The expression level of PDI genes was compared between wheat cultivars and lines with different genotype-phenotype combinations, which means diversified sets of HMW-GS combined with diversified qualitative classification. The highest expression level of PDI was noticed at early stage of grain development, which is consistent with the function of PDI. The expression level was evaluated by the real-time PCR technique.

CONCLUSION: Results obtained in this work did not allow for a clear statement of decisive significance of PDI in the context of shaping the final baking value. The results of this work contribute to an ever more in-depth understanding of the mechanisms governing baking value, and thus to the progress of the selection of new varieties with more beneficial properties.}, } @article {pmid30466385, year = {2018}, author = {Lai, YP and Ioerger, TR}, title = {A statistical method to identify recombination in bacterial genomes based on SNP incompatibility.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {450}, pmid = {30466385}, issn = {1471-2105}, mesh = {Genome, Bacterial/*genetics ; *Phylogeny ; Polymorphism, Single Nucleotide/*genetics ; Recombination, Genetic/*genetics ; }, abstract = {BACKGROUND: Phylogeny estimation for bacteria is likely to reflect their true evolutionary histories only if they are highly clonal. However, recombination events could occur during evolution for some species. The reconstruction of phylogenetic trees from an alignment without considering recombination could be misleading, since the relationships among strains in some parts of the genome might be different than in others. Using a single, global tree can create the appearance of homoplasy in recombined regions. Hence, the identification of recombination breakpoints is essential to better understand the evolutionary relationships of isolates among a bacterial population.

RESULTS: Previously, we have developed a method (called ACR) to detect potential breakpoints in an alignment by evaluating compatibility of polymorphic sites in a sliding window. To assess the statistical significance of candidate breakpoints, we propose an extension of the algorithm (ptACR) that applies a permutation test to generate a null distribution for comparing the average local compatibility. The performance of ptACR is evaluated on both simulated and empirical datasets. ptACR is shown to have similar sensitivity (true positive rate) but a lower false positive rate and higher F1 score compared to basic ACR. When used to analyze a collection of clinical isolates of Staphylococcus aureus, ptACR finds clear evidence of recombination events in this bacterial pathogen, and is able to identify statistically significant boundaries of chromosomal regions with distinct phylogenies.

CONCLUSIONS: ptACR is an accurate and efficient method for identifying genomic regions affected by recombination in bacterial genomes.}, } @article {pmid30465644, year = {2019}, author = {Liu, SW and Li, FN and Qi, X and Xie, YY and Sun, CH}, title = {Nakamurella deserti sp. nov., isolated from rhizosphere soil of Reaumuria in the Taklamakan desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {214-219}, doi = {10.1099/ijsem.0.003132}, pmid = {30465644}, issn = {1466-5034}, abstract = {A Gram-stain-positive, aerobic, non-motile, non-spore-forming, coccus-shaped actinobacterium, designated strain 12Sc4-1T, was isolated from a soil sample collected in the Taklamakan desert in Xinjiang Uygur Autonomous Region, China. Strain 12Sc4-1T grew at 8‒35 °C (optimum, 28‒30 °C), pH 6.0‒9.0 (optimum, pH 7.0) and in the presence of 0‒3 % (w/v) NaCl (optimum, 0 %). Phylogenetic analysis based on 16S rRNA gene sequence suggested that strain 12Sc4-1T belonged to the genus Nakamurella and shared the highest 16S rRNA gene sequence similarity to Nakamurella silvestris S20-107T (96.94 %). Strain 12Sc4-1T showed <96.0 % 16S rRNA gene sequence similarities to all other recognized members of the genus Nakamurella. Chemotaxonomic analyses showed that the isolate possessed meso-diaminopimelic acid as the diagnostic diamino acid of the peptidoglycan, glucose, mannose and galactose as whole-cell sugars, and MK-8(H4) as the predominant menaquinone. The polar lipids comprised diphosphatidylglycerol, phosphatidylethanolamine, an unidentified aminophospholipid, phosphatidylinositol, an unidentified phospholipid, an unidentified phosphoglycolipid and an unidentified glycolipid. The major fatty acids were C16 : 0 and anteiso-C15 : 0. The DNA G+C content was 72.1 mol% (draft genome sequence). On the basis of phylogenetic, phenotypic and chemotaxonomic analyses, strain 12Sc4-1T represents a novel species of the genus Nakamurella, for which the name Nakamurelladeserti sp. nov. is proposed. The type strain is 12Sc4-1T (=KCTC 49114T=CGMCC 1.16555T).}, } @article {pmid30465643, year = {2019}, author = {Hoetzinger, M and Schmidt, J and Pitt, A and Koll, U and Lang, E and Hahn, MW}, title = {Polynucleobacter paneuropaeus sp. nov., characterized by six strains isolated from freshwater lakes located along a 3000 km north-south cross-section across Europe.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {203-213}, doi = {10.1099/ijsem.0.003130}, pmid = {30465643}, issn = {1466-5034}, abstract = {Six Polynucleobacter (Burkholderiaceae, Betaproteobacteria) strains isolated from different freshwater lakes located across Europe were taxonomically investigated. Phylogenetic analyses based on 16S rRNA gene sequences assigns all six strains to the cryptic species complex PnecC within the genus Polynucleobacter. Analyses of partial glutamine synthetase (glnA) genes suggests that all six strains belong to the species-like taxon designated F15 in previous papers. Comparative genome analyses reveal that the six strains form a genomically coherent group characterized by whole-genome average nucleotide identity (gANI) values of >98 % but separated by gANI values of <88 % from the type strains and representatives of the 16 previously described Polynucleobacter species. In phylogenetic analyses based on nucleotide sequences of 319 orthologous genes, the six strains represent a monophyletic cluster that is clearly separated from all other described species. Genome sizes of the six strains range from 1.61 to 1.83 Mbp, which is smaller than genome sizes of the majority of type strains representing previously described Polynucleobacter species. By contrast, the G+C content of the DNA of the strains is well in the range of 44.8-46.6 mol% previously found for other type strains of species affiliated with the subgroup PnecC. Variation among the six strains representing the new species is evident in a number of traits. These include gene content differences, for instance regarding a gene cluster encoding anoxygenic photosynthesis, as well as phenotypic traits. We propose to name the new species represented by the six strains Polynucleobacter paneuropaeus sp. nov. and designate strain MG-25-Pas1-D2T (=DSM 103454T =CIP 111323T) as the type strain.}, } @article {pmid30465641, year = {2018}, author = {Yao, L and Lai, Y and Xue, F and Sun, L and Wang, J}, title = {Paracandidimonas caeni sp. nov., isolated from sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003131}, pmid = {30465641}, issn = {1466-5034}, abstract = {A beige-pigmented, Gram-stain-negative, aerobic, non-motile, rod-shaped bacterium, named 24T, was isolated from sludge of a pesticide manufacturing factory in Nantong, Jiangsu Province, China. 16S rRNA gene sequence analysis revealed that strain 24T shared highest similarity with Parapusillimonas granuli Ch07T (98.20 %), followed by Candidimonas nitroreducens SC-089T (98.07 %) and Paracandidimonas soli IMT-305T (98.03 %). Phylogenetic trees showed that strain 24T formed a distinct clade with Paracandidimonas soli IMT-305T. The results of DNA-DNA hybridization tests showed that reassociation values were less than 45 % with respect to these closely related type strains. Strain 24T contained Q-8 and putrescine as the major respiratory quinone and polyamine, respectively. The main cellular fatty acids were summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), summed feature 2 (iso-C16 : 1 I/C14 0 3-OH/C12 : 0 aldehyde), summed feature 8 (C18 : 1ω7c/C18 : 1ω6c) and C12 : 0. The polar lipid profile included phosphatidylmethylethanolamin, phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid and one unidentified aminolipid. The G+C content was 56.83 mol%. Combined data from phenotypic, phylogenetic and DNA-DNA relatedness studies demonstrated that strain 24T represents a novel species of the genus Paracandidimonas, for which the name Paracandidimonas caeni sp. nov. is proposed. The type strain is 24T (=CCTCC AB 2018057T=KACC 19692T).}, } @article {pmid30465640, year = {2019}, author = {Boujida, N and Palau, M and Charfi, S and Manresa, À and Skali Senhaji, N and Abrini, J and Miñana-Galbis, D}, title = {Marinobacter maroccanus sp. nov., a moderately halophilic bacterium isolated from a saline soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {227-234}, doi = {10.1099/ijsem.0.003134}, pmid = {30465640}, issn = {1466-5034}, abstract = {During the taxonomic investigation of exopolymer-producing halophilic bacteria, a rod-shaped, motile, Gram-stain-negative, halophilic bacterium, designated strain N4T, was isolated from a saline soil located in northern Morocco. Optimal growth of the isolate was at 30-37 ºC and at pH 7.0-8.0, in the presence of 5-7 % (w/v) NaCl. Useful characteristics for the phenotypic differentiation of strain N4T from other Marinobacter species included α-chymotrypsin and α-glucosidase activities and the carbohydrate assimilation profile. The major fatty acids detected in strain N4T were C16:0 and C18:1ω9c and the predominant respiratory quinone was ubiquinone-9. Sequence analysis of the 16S rRNA gene indicated that strain N4T belonged to the genus Marinobacter and was closely related to the type strains of Marinobacter adhaerens (99.04 % similarity), Marinobacter salsuginis (98.97 %) and Marinobacter flavimaris (98.36 %). Phylogenetic analysis of the rpoD gene sequence also showed that the nearest neighbours of strain N4T were M. salsuginis (91.49 % similarity), M. adhaerens and M. flavimaris (90.63 %). Strain N4T showed 87.98 % average nucleotide identity with M. flavimaris and M. salsuginis, and 87.47 % with M. adhaerens. Regarding in-silico genome-to-genome distance, strain N4T showed DNA-DNA hybridization values of 33.30 % with M. adhaerens, 34.60 % with M. flavimaris and 34.70 % with M. salsuginis. The DNA G+C content of strain N4T was 57.3 mol%. Based on the results of phenotypic characterization, phylogenetic analysis and genome comparison, strain N4T represents a novel species of the genus Marinobacter, for which the name Marinobacter maroccanus sp. nov. is proposed. The type strain is N4T (=CECT 9525T=LMG 30466T).}, } @article {pmid30465639, year = {2019}, author = {Gao, ZH and Ruan, SL and Huang, YX and Lv, YY and Qiu, LH}, title = {Paraburkholderia phosphatilytica sp. nov., a phosphate-solubilizing bacterium isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {196-202}, doi = {10.1099/ijsem.0.003129}, pmid = {30465639}, issn = {1466-5034}, abstract = {A novel Gram-stain-negative, aerobic, non-spore-forming, non-motile and rod-shaped bacterial strain, 7QSK02T, was isolated from forest soil of Dinghushan Biosphere Reserve, Guangdong Province, China. It grew at 12-37 °C, at pH 4.0-7.5 and in the presence of 0-1.0 % (w/v) NaCl on R2A agar medium, with optimum growth at 28 °C, pH 5.5 and 0 % NaCl. Strain 7QSK02T was closely related to members of the genus Paraburkholderia: P. acidipaludis NBRC 101816T (98.1 % 16S rRNA gene sequence similarity), P. piptadeniae STM 7183T (97.6 %), P. kururiensis JCM 10599T (97.3 %), P. caballeronis TNe-841T (97.3 %) and P. diazotrophica JPY461T (97.1 %). 16S rRNA gene sequence analysis showed that strain 7QSK02T and two closely strains, P. kururiensis JCM 10599T and P. caballeronis TNe-841T, formed a clade within the genus Paraburkholderia, but was clearly separated from the established species. The genomic G+C content of strain 7QSK02T was 64.9 mol% based on total genome calculations. The average nucleotide identity and digital DNA-DNA hybridization value for the complete genomes were 79.2-81.5 and 23.2-24.9 % between strain 7QSK02T and its closely related species listed above. Strain 7QSK02T contained ubiquinone 8 as the major respiratory quinone. Major fatty acids were C16 : 0, C17 : 0 cyclo and C19 : 0 cyclo ω8c. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmethylethanolamine, one unidentified aminophospholipid, aminolipid and polar lipid. The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis suggest that strain 7QSK02T represents a novel species of the genus Paraburkholderia, for which the name Paraburkholderia phosphatilytica sp. nov. is proposed. The type strain is 7QSK02T (=GDMCC 1.1283T=CGMCC 1.15470T=KCTC 62473T).}, } @article {pmid30464833, year = {2018}, author = {Moore, JM and Carvajal, JI and Rouse, GW and Wilson, NG}, title = {The Antarctic Circumpolar Current isolates and connects: Structured circumpolarity in the sea star Glabraster antarctica.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10621-10633}, pmid = {30464833}, issn = {2045-7758}, abstract = {Aim: The Antarctic Circumpolar Current (ACC) connects benthic populations by transporting larvae around the continent, but also isolates faunas north and south of the Antarctic Convergence. We test circumpolar panmixia and dispersal across the Antarctic Convergence barrier in the benthic sea star Glabraster antarctica.

Location: The Southern Ocean and south Atlantic Ocean, with comprehensive sampling including the Magellanic region, Scotia Arc, Antarctic Peninsula, Ross Sea, and East Antarctica.

Methods: The cytochrome c oxidase subunit I (COI) gene (n = 285) and the internal transcribed spacer region 2 (ITS2; n = 33) were sequenced. We calculated haplotype networks for each genetic marker and estimated population connectivity and the geographic distribution of genetic structure using ΦST for COI data.

Results: Glabraster antarctica is a single circum-Antarctic species with instances of gene flow between distant locations. Despite the homogenizing potential of the ACC, population structure is high (ΦST = 0.5236), and some subpopulations are genetically isolated. Genetic breaks in the Magellanic region do not align with the Antarctic Convergence, in contrast with prior studies. Connectivity patterns in East Antarctic sites are not uniform, with some regional isolation and some surprising affinities to the distant Magellanic and Scotia Arc regions.

Main conclusions: Despite gene flow over extraordinary distances, there is strong phylogeographic structuring and genetic barriers evident between geographically proximate regions (e.g., Shag Rocks and South Georgia). Circumpolar panmixia is rejected, although some subpopulations show a circumpolar distribution. Stepping-stone dispersal occurs within the Scotia Arc but does not appear to facilitate connectivity across the Antarctic Convergence. The patterns of genetic connectivity in Antarctica are complex and should be considered in protected area planning for Antarctica.}, } @article {pmid30464832, year = {2018}, author = {Elayadeth-Meethal, M and Thazhathu Veettil, A and Maloney, SK and Hawkins, N and Misselbrook, TH and Sejian, V and Rivero, MJ and Lee, MRF}, title = {Size does matter: Parallel evolution of adaptive thermal tolerance and body size facilitates adaptation to climate change in domestic cattle.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10608-10620}, pmid = {30464832}, issn = {2045-7758}, abstract = {The adaptive potential of livestock under a warming climate is increasingly relevant in relation to the growing pressure of global food security. Studies on heat tolerance demonstrate the interplay of adaptation and acclimatization in functional traits, for example, a reduction in body size and enhanced tolerance in response to a warming climate. However, current lack of understanding of functional traits and phylogenetic history among phenotypically distinct populations constrains predictions of climate change impact. Here, we demonstrate evidence of parallel evolution in adaptive tolerance to heat stress in dwarf cattle breeds (DCB, Bos taurus indicus) and compare their thermoregulatory responses with those in standard size cattle breeds (SCB, crossbred, Bos taurus indicus × Bos taurus taurus). We measured vital physiological, hematological, biochemical, and gene expression changes in DCB and SCB and compared the molecular phylogeny using mitochondrial genome (mitogenome) analysis. Our results show that SCB can acclimatize in the short term to higher temperatures but reach their tolerance limit under prevailing tropical conditions, while DCB is adapted to the warmer climate. Increased hemoglobin concentration, reduced cellular size, and smaller body size enhance thermal tolerance. Mitogenome analysis revealed that different lineages of DCB have evolved reduced size independently, as a parallel adaptation to heat stress. The results illustrate mechanistic ways of dwarfing, body size-dependent tolerance, and differential fitness in a large mammal species under harsh field conditions, providing a background for comparing similar populations during global climate change. These demonstrate the value of studies combining functional, physiological, and evolutionary approaches to delineate adaptive potential and plasticity in domestic species. We thus highlight the value of locally adapted breeds as a reservoir of genetic variation contributing to the global domestic genetic resource pool that will become increasingly important for livestock production systems under a warming climate.}, } @article {pmid30464831, year = {2018}, author = {Clarke, PMR and McElreath, MB and Barrett, BJ and Mabry, KE and McElreath, R}, title = {The evolution of bequeathal in stable habitats.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10594-10607}, pmid = {30464831}, issn = {2045-7758}, abstract = {Adults sometimes disperse, while philopatric offspring inherit the natal site, a pattern known as bequeathal. Despite a decades-old empirical literature, little theoretical work has explored when natural selection may favor bequeathal. We present a simple mathematical model of the evolution of bequeathal in a stable environment, under both global and local dispersal. We find that natural selection favors bequeathal when adults are competitively advantaged over juveniles, baseline mortality is high, the environment is unsaturated, and when juveniles experience high dispersal mortality. However, frequently bequeathal may not evolve, because the fitness cost for the adult is too large relative to inclusive fitness benefits. Additionally, there are many situations for which bequeathal is an ESS, yet cannot invade the population. As bequeathal in real populations appears to be facultative, yet-to-be-modeled factors like timing of birth in the breeding season may strongly influence the patterns seen in natural populations.}, } @article {pmid30464830, year = {2018}, author = {Li, S and Qian, X and Zheng, Z and Shi, M and Chang, X and Li, X and Liu, J and Tu, T and Zhang, D}, title = {DNA barcoding the flowering plants from the tropical coral islands of Xisha (China).}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10587-10593}, pmid = {30464830}, issn = {2045-7758}, abstract = {Aim: DNA barcoding has been widely applied to species diversity assessment in various ecosystems, including temperate forests, subtropical forests, and tropical rain forests. However, tropical coral islands have never been barcoded before due to the difficulties in field exploring. This study aims at barcoding the flowering plants from a unique ecosystem of the tropical coral islands in the Pacific Ocean and supplying valuable evolutionary information for better understanding plant community assembly of those particular islands in the future.

Location: Xisha Islands, China.

Methods: This study built a DNA barcode database for 155 plant species from the Xisha Islands using three DNA markers (ITS, rbcL, and matK). We applied the sequence similarity method and a phylogenetic-based method to assess the barcoding resolution.

Results: All the three DNA barcodes showed high levels of PCR success (96%-99%) and sequencing success (98%-100%). ITS performed the highest rate of species resolution (>95%) among the three markers, while plastid markers delivered a relatively poor species resolution (85%-90%). Our analyses obtained a marginal increase in species resolution when combining the three DNA barcodes.

Main conclusions: This study provides the first plant DNA barcode data for the unique ecosystem of tropical coral islands and considerably supplements the DNA barcode library for the flowering plants on the oceanic islands. Based on the PCR and sequencing success rates, and the discriminatory power of the three DNA regions, we recommend ITS as the most successful DNA barcode to identify the flowering plants from Xisha Islands. Due to its high sequence variation and low fungal contamination, ITS could be a preferable candidate of DNA barcode for plants from other tropical coral islands as well. Our results also shed lights on the importance of biodiversity conservation of tropical coral islands.}, } @article {pmid30464829, year = {2018}, author = {Boundenga, L and Ngoubangoye, B and Mombo, IM and Tsoubmou, TA and Renaud, F and Rougeron, V and Prugnolle, F}, title = {Extensive diversity of malaria parasites circulating in Central African bats and monkeys.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10578-10586}, pmid = {30464829}, issn = {2045-7758}, abstract = {The order Haemosporidia gathers many protozoan parasites which are known to infect many host species and groups. Until recently, the studies on haemosporidian parasites primarily focused on the genus Plasmodium among a wide range of hosts. Genera, like the genus Hepatocystis, have received far less attention. In the present study, we present results of a survey of the diversity of Hepatocystis infecting bats and monkeys living in a same area in Gabon (Central Africa). Phylogenetic analyses revealed a large diversity of Hepatocystis lineages circulating among bats and monkeys, among which certain were previously observed in other African areas. Both groups of hosts harbor parasites belonging to distinct genetic clades and no transfers of parasites were observed between bats and monkeys. Finally, within each host group, no host specificity or geographical clustering was observed for the bat or the primate Hepatocystis lineages.}, } @article {pmid30464828, year = {2018}, author = {Verschut, TA and Inouye, BD and Hambäck, PA}, title = {Sensory deficiencies affect resource selection and associational effects at two spatial scales.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10569-10577}, pmid = {30464828}, issn = {2045-7758}, abstract = {Many insect species have limited sensory abilities and may not be able to perceive the quality of different resource types while approaching patchily distributed resources. These restrictions may lead to differences in selection rates between separate patches and between different resource types within a patch, which may have consequences for associational effects between resources. In this study, we used an oviposition assay containing different frequencies of apple and banana substrates divided over two patches to compare resource selection rates of wild-type Drosophila melanogaster at the between- and within-patch scales. Next, we compared the wild-type behavior with that of the olfactory-deficient strain Orco2 and the gustatory-deficient strain PoxnΔM22-B5 and found comparable responses to patch heterogeneity and similarly strong selection rates for apple at both scales for the wild-type and olfactory-deficient flies. Their oviposition behavior translated into associational susceptibility for apple and associational resistance for banana. The gustatory-deficient flies, on the other hand, no longer had a strong selection rate for apple, strongly differed in between- and within-patch selection rates from the wild-type flies, and caused no associational effects between the resources. Our study suggests that differences in sensory capabilities can affect resource selection at different search behavior scales in different ways and in turn underlie associational effects between resources at different spatial scales.}, } @article {pmid30464827, year = {2018}, author = {Franks, SE and Roodbergen, M and Teunissen, W and Carrington Cotton, A and Pearce-Higgins, JW}, title = {Evaluating the effectiveness of conservation measures for European grassland-breeding waders.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10555-10568}, pmid = {30464827}, issn = {2045-7758}, abstract = {Farmland birds are among the most threatened bird species in Europe, largely as a result of agricultural intensification which has driven widespread biodiversity losses. Breeding waders associated with grassland and arable habitats are particularly vulnerable and a frequent focus of agri-environment schemes (AES) designed to halt and reverse population declines. We review existing literature, providing a quantitative assessment of the effectiveness of policy and management interventions used throughout Europe to improve population and demographic metrics of grassland-breeding waders. Targeted AES and site protection measures were more likely to be effective than less targeted AES and were ten times more likely to be effective than would be expected by chance, particularly for population trend and productivity metrics. Positive effects of AES and site protection did not appear synergistic. Management interventions which had the greatest chance of increasing population growth or productivity included modification of mowing regimes, increasing wet conditions, and the use of nest protection. Success rates varied according to the species and metric being evaluated. None of the policy or management interventions we evaluated were associated with a significant risk of negative impacts on breeding waders. Our findings support the use of agri-environment schemes, site protection, and management measures for grassland-breeding wader conservation in Europe. Due to publication bias, our findings are most applicable to intensively managed agricultural landscapes. More studies are needed to identify measures that increase chick survival. Despite broadly effective conservation measures already in use, grassland-breeding waders in Europe continue to decline. More research is needed to improve the likelihood and magnitude of positive outcomes, coupled with wider implementation of effective measures to substantially increase favorable land management for these species.}, } @article {pmid30464826, year = {2018}, author = {Thapa, A and Wu, R and Hu, Y and Nie, Y and Singh, PB and Khatiwada, JR and Yan, L and Gu, X and Wei, F}, title = {Predicting the potential distribution of the endangered red panda across its entire range using MaxEnt modeling.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10542-10554}, pmid = {30464826}, issn = {2045-7758}, abstract = {An upsurge in anthropogenic impacts has hastened the decline of the red panda (Ailurus fulgens). The red panda is a global conservation icon, but holistic conservation management has been hampered by research being restricted to certain locations and population clusters. Building a comprehensive potential habitat map for the red panda is imperative to advance the conservation effort and ensure coordinated management across international boundaries. Here, we use occurrence records of both subspecies of red pandas from across their entire range to build a habitat model using the maximum entropy algorithm (MaxEnt 3.3.3k) and the least correlated bioclimatic variables. We found that the subspecies have separate climatic spaces dominated by temperature-associated variables in the eastern geographic distribution limit and precipitation-associated variables in the western distribution limit. Annual precipitation (BIO12) and maximum temperature in the warmest months (BIO5) were major predictors of habitat suitability for A. f. fulgens and A. f. styani, respectively. Our model predicted 134,975 km2 of red panda habitat based on 10 percentile thresholds in China (62% of total predicted habitat), Nepal (15%), Myanmar (9%), Bhutan (9%), and India (5%). Existing protected areas (PAs) encompass 28% of red panda habitat, meaning the PA network is currently insufficient and alternative conservation mechanisms are needed to protect the habitat. Bhutan's PAs provide good coverage for the red panda habitat. Furthermore, large areas of habitat were predicted in cross-broader areas, and transboundary conservation will be necessary.}, } @article {pmid30464825, year = {2018}, author = {Trukhanova, IS and Conn, PB and Boveng, PL}, title = {Taxonomy-based hierarchical analysis of natural mortality: polar and subpolar phocid seals.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10530-10541}, pmid = {30464825}, issn = {2045-7758}, abstract = {Knowledge of life-history parameters is frequently lacking in many species and populations, often because they are cryptic or logistically challenging to study, but also because life-history parameters can be difficult to estimate with adequate precision. We suggest using hierarchical Bayesian analysis (HBA) to analyze variation in life-history parameters among related species, with prior variance components representing shared taxonomy, phenotypic plasticity, and observation error. We develop such a framework to analyze U-shaped natural mortality patterns typical of mammalian life history from a variety of sparse datasets. Using 39 datasets from seals in the family Phocidae, we analyzed 16 models with different formulations for natural morality, specifically the amount of taxonomic and data-level variance components (subfamily, species, study, and dataset levels) included in mortality hazard parameters. The highest-ranked model according to DIC included subfamily-, species-, and dataset-level parameter variance components and resulted in typical U-shaped hazard functions for the 11 seal species in the study. Species with little data had survival schedules shrunken to the mean. We suggest that evolutionary and population ecologists consider employing HBA to quantify variation in life-history parameters. This approach can be useful for increasing the precision of estimates resulting from a collection of (often sparse) datasets, and for producing prior distributions for populations missing life-history data.}, } @article {pmid30464824, year = {2018}, author = {Dias, MP and Carneiro, APB and Warwick-Evans, V and Harris, C and Lorenz, K and Lascelles, B and Clewlow, HL and Dunn, MJ and Hinke, JT and Kim, JH and Kokubun, N and Manco, F and Ratcliffe, N and Santos, M and Takahashi, A and Trivelpiece, W and Trathan, PN}, title = {Identification of marine Important Bird and Biodiversity Areas for penguins around the South Shetland Islands and South Orkney Islands.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10520-10529}, pmid = {30464824}, issn = {2045-7758}, abstract = {Aim: To provide a method of analyzing penguin tracking data to identify priority at-sea areas for seabird conservation (marine IBAs), based on pre-existing approaches for flying seabirds but revised according to the specific ecology of Pygoscelis penguin species.

Location: Waters around the Antarctic Peninsula, South Shetland, and South Orkney archipelagos (FAO Subareas 48.1 and 48.2).

Methods: We made key improvements to the pre-existing protocol for identifying marine IBAs that include refining the track interpolation method and revision of parameters for the kernel analysis (smoothing factor and utilization distribution) using sensitivity tests. We applied the revised method to 24 datasets of tracking data on penguins (three species, seven colonies, and three different breeding stages-incubation, brood, and crèche).

Results: We identified five new marine IBAs for seabirds in the study area, estimated to hold ca. 600,000 adult penguins.

Main conclusions: The results demonstrate the efficacy of a new method for the designation of a network of marine IBAs in Antarctic waters for penguins based on tracking data, which can contribute to an evidence-based, precautionary, management framework for krill fisheries.}, } @article {pmid30464823, year = {2018}, author = {Christian, K and Weitzman, C and Rose, A and Kaestli, M and Gibb, K}, title = {Ecological patterns in the skin microbiota of frogs from tropical Australia.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10510-10519}, pmid = {30464823}, issn = {2045-7758}, abstract = {The microbiota of frog skin can play an important role in protecting against diseases and parasites. The frog skin microbial community represents a complex mix of microbes that are promoted by the chemical environment of the frog skin and influenced by the animal's immediate past environment. The microbial communities of six species of frogs sampled from the campus of Charles Darwin University (CDU) were more similar within species than between species. The microbiota of the introduced cane toad (Rhinella marina) was most dissimilar among the species. Pairwise comparisons showed that the microbial communities of each species were different, except for the terrestrial Litoria nasuta and the arboreal L. rothii. The microbial communities of the six species were not related to ecological habit (arboreal or terrestrial), and neither was the alpha diversity of the microbes. The core microbes (defined as being on ≥90% of individuals of a species or group) were significantly different among all species, although 89 microbial operational taxonomic units (OTUs) were core microbes for all six species at CDU. Two species, Rhinella marina and Litoria rothii, were sampled at additional sites approximately 10 and 30 km from CDU. The microbial communities and the core OTU composition were different among the sites, but there were nevertheless 194 (R. marina) and 181 (L. rothii) core OTUs present at all three sites. Thus, the core microbiota varied with respect to geographic range and sample size.}, } @article {pmid30464822, year = {2018}, author = {Sarquis, JA and Cristaldi, MA and Arzamendia, V and Bellini, G and Giraudo, AR}, title = {Species distribution models and empirical test: Comparing predictions with well-understood geographical distribution of Bothrops alternatus in Argentina.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10497-10509}, pmid = {30464822}, issn = {2045-7758}, abstract = {Species distribution models (SDMs) estimate the geographical distribution of species although with several limitations due to sources of inaccuracy and biases. Empirical tests arose as the most important steps in scientific knowledge to assess the efficiency of model predictions, which are poorly rigorous in SDMs. A good approach to the empirical distribution (ED) of a species can be obtained from comprehensive empirical knowledge, that is, well-understood distributions gathered from large amount of data generated with appropriate spatial and temporal samples coverage. The aims of this study were to (a) compare different SDMs predictions with an ED; and (b) evaluate if fuzzy global matching (FGM) could be used as an index to compare SDMs predictions and ED. Six algorithms with 5 and 20 variables were used to assess their accuracy in predicting the ED of the venomous snake Bothrops alternatus (Viperidae). Its entire distribution is known, thanks to thorough field surveys across Argentina, with 1,767 records. ED was compared with SDMs predictions using Map Comparison Kit. SDMs predictions showed important biases in all methods used, from 70% sub-estimation to 40% over-estimation of ED. BIOCLIM predicted ≈31% of B. alternatus ED. DOMAIN predicted 99% of ED, but over-estimated 40% of the area. GLM with five variables calculated 75% of ED, while Genetic Algorithm for Rule-set Prediction showed ≈60% of ED; the last two presenting overpredictions in areas with favorable climatic conditions but not inhabited by the species. MaxEnt and RF were the only methods to detect isolated populations in the southern distribution of B. alternatus. Although SDMs proved useful in making predictions about species distribution, predictions need validation with expert maps knowledge and ED. Moreover, FGM showed a good performance as an index with values similar to True Skill Statistic, so that it could be used to relate ED and SDMs predictions.}, } @article {pmid30464821, year = {2018}, author = {Laursen, K and Balbontín, J and Thorup, O and Haaning Nielsen, H and Asferg, T and Møller, AP}, title = {Multiple components of environmental change drive populations of breeding waders in seminatural grasslands.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10489-10496}, pmid = {30464821}, issn = {2045-7758}, abstract = {Environments are rapidly changing due to climate change, land use, intensive agriculture, and the impact of hunting on predator populations. Here, we analyzed long-term data recorded during 1928-2014 on the size of breeding populations of waders at two large nature reserves in Denmark, Vejlerne and Tipperne, to determine the effects of components of environmental change on breeding populations of waders. Environmental variables and counts of waders were temporally autocorrelated, and we used generalized least square (GLS) by incorporating the first-order autoregressive correlation structure in the analyses. We attempted to predict the abundance of waders for short-term trends for two nature reserves (35 years) and for long-term trends for one nature reserve (86 years), using precipitation, temperature, nutrients, abundance of foxes Vulpes vulpes, area grazed, and number of cattle. There was evidence of impacts of nutrients, climate (long-term changes in temperature and precipitation), grazing, mowing, and predation on bird populations. We used standard random effects meta-analyses weighted by (N-3) to quantify these mean effects. There was no significant difference in effect size among species, while mean effect size differed consistently among environmental factors, and the interaction between effect size for species and environmental factors was also significant. Thus, environmental factors affected the different species differently. Mean effect size was the largest at +0.20 for rain, +0.11 for temperature, -0.09 for fox abundance, and -0.03 for number of cattle, while there was no significant mean effect for fertilizer, area grazed, and year. Effect sizes for two short-term time series from Tipperne and Vejlerne were positively correlated as were effect sizes for short-term and long-term time series at Tipperne. This implies that environmental factors had consistent effects across large temporal and spatial scales.}, } @article {pmid30464820, year = {2018}, author = {Ocampo, D and Barrantes, G and Uy, JAC}, title = {Morphological adaptations for relatively larger brains in hummingbird skulls.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10482-10488}, pmid = {30464820}, issn = {2045-7758}, abstract = {A common allometric pattern called Haller's Rule states that small species have relatively larger brains and eyes than larger species of the same taxonomic group. This pattern imposes drastic structural changes and energetic costs on small species to produce and maintain a disproportionate amount of nervous tissue. Indeed, several studies have shown the significant metabolic costs of having relatively larger brains; however, little is known about the structural constraints and adaptations required for housing these relatively larger brains and eyes. Because hummingbirds include the smallest birds, they are ideal for exploring how small species evolve morphological adaptations for housing relatively larger brain and eyes. We here present results from a comparative study of hummingbirds and show that the smallest species have the lowest levels of ossification, the most compact braincases, and relatively larger eye sockets, but lower eye/head proportion, than larger species. In contrast to Passerines, skull ossification in hummingbirds correlates with body and brain size but not with age. Correlation of these skull traits with body size might represent adaptations to facilitate housing relatively larger brain and eyes, rather than just heterochronic effects related to change in body size. These structural changes in skull traits allow small animals to accommodate disproportionately larger brains and eyes without further increasing overall head size.}, } @article {pmid30464819, year = {2018}, author = {Symons, J and Sprogis, KR and Bejder, L}, title = {Implications of survey effort on estimating demographic parameters of a long-lived marine top predator.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10470-10481}, pmid = {30464819}, issn = {2045-7758}, abstract = {Effective management of wildlife populations rely on knowledge of their abundance, survival, and reproductive rates. Maintaining long-term studies capable of estimating demographic parameters for long-lived, slow-reproducing species is challenging. Insights into the effects of research intensity on the statistical power to estimate demographic parameters are limited. Here, we investigate implications of survey effort on estimating abundance, home range sizes, and reproductive output of Indo-Pacific bottlenose dolphins (Tursiops aduncus), using a 3-year subsample of a long-term, capture-recapture study off Bunbury, Western Australia. Photo-identification on individual dolphins was collected following Pollock's Robust Design, where seasons were defined as "primary periods", each consisting of multiple "secondary periods." The full dataset consisted of 12 primary periods and 72 secondary periods, resulting in the study area being surveyed 24 times/year. We simulated reduced survey effort by randomly removing one, two, or three secondary periods per primary period. Capture-recapture models were used to assess the effect of survey intensity on the power to detect trends in population abundance, while individual dolphin sighting histories were used to assess the ability to conduct home range analyses. We used sighting records of adult females and their calving histories to assess survey effort on quantifying reproductive output. A 50% reduction in survey effort resulted in (a) up to a 36% decline in population abundance at the time of detection; (b) a reduced ability to estimate home range sizes, by increasing the time for individuals to be sighted on ≥30 occasions (an often-used metric for home range analyses) from 7.74 to 14.32 years; and (c) 33%, 24%, and 33% of annual calving events across three years going undocumented, respectively. Results clearly illustrate the importance of survey effort on the ability to assess demographic parameters with clear implications for population viability analyses, population forecasting, and conservation efforts to manage human-wildlife interactions.}, } @article {pmid30464818, year = {2018}, author = {Duxbury, AE and Weathersby, B and Sanchez, Z and Moore, PJ}, title = {A study of the transit amplification divisions during spermatogenesis in Oncopetus fasciatus to assess plasticity in sperm numbers or sperm viability under different diets.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10460-10469}, pmid = {30464818}, issn = {2045-7758}, abstract = {Oncopeltus fasciatus males fed the ancestral diet of milkweed seeds prioritize reproduction over lifespan as evidenced by higher rates of fertility and shorter lifespans than males from the same population fed the adapted diet of sunflower seeds. We examined the proximate mechanisms by which milkweed-fed males maintained late-life fertility. We tested the hypothesis that older milkweed-fed males maintained fertility by producing more, higher quality sperm. Our results, that older males have more sperm, but their sperm do not have higher viability, are in general agreement with other recent studies on how nutrition affects male fertility in insects. We further examined the mechanisms by which sperm are produced by examining the progression of spermatogonial cells through the cell cycle during the transit amplification divisions. We demonstrated that diet affects the likelihood of a spermatocyst being in the S-phase or M-phase of the cell cycle. Given work in model systems, these results have implications for subtle effects on sperm quality either through replication stress or epigenetic markers. Thus, viability may not be the best marker for sperm quality and more work is called for on the mechanisms by which the germline and the production of sperm mediate the cost of reproduction.}, } @article {pmid30464817, year = {2018}, author = {Sunde, J and Tibblin, P and Larsson, P and Forsman, A}, title = {Sex-specific effects of outbreeding on offspring quality in pike (Esox lucius).}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10448-10459}, pmid = {30464817}, issn = {2045-7758}, abstract = {Intraspecific genetic admixture occurs when previously separated populations within a species start interbreeding, and it can have either positive, negative, or neutral effects on reproductive performance. As there currently is no reliable predictor for the outcome of admixture, an increased knowledge about admixture effects in different species and populations is important to increase the understanding about what determines the response to admixture. We tested for effects of admixture on F1 offspring quality in three subpopulations of pike (Esox lucius). Gametes were collected in the field, and eggs from each female were experimentally fertilized with milt from a male from each population (one "pure" and two "admixed" treatments). Three offspring quality measures (hatching success, fry survival, and fry length) were determined and compared between (a) pure and admixed population combinations and (b) the sex-specific treatments within each admixed population combination (based on the origin of the male and female, respectively). The results suggested that although there were no overall effects of admixture on offspring quality, the consequences for a given population combination could be sex-specific and thus differ depending on which of the parents originated from one or the other population. All offspring quality traits were influenced by both maternal ID and paternal ID. Sex- and individual-specific effects can have implications for dispersal behavior and gene flow between natural populations, and are important to consider in conservation efforts.}, } @article {pmid30464816, year = {2018}, author = {Riccioni, G and Stagioni, M and Piccinetti, C and Libralato, S}, title = {A metabarcoding approach for the feeding habits of European hake in the Adriatic Sea.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10435-10447}, pmid = {30464816}, issn = {2045-7758}, abstract = {European hake (Merluccius merluccius) is one of the most economically important fish for the Mediterranean Sea. It is an important predator of deep upper shelf slope communities currently characterized by growth overexploitation: the understanding of hake's diet might support next generation management tools. However, all current European hake diet studies depend on the morphological identification of prey remains in stomach content, with consequent limitations. In this study, we set up a metabarcoding approach based on cytochrome oxidase I PCR amplification and Miseq Illumina paired-end sequencing of M. merluccius stomach content remains and compared the results to classic morphological analyses. A total of 95 stomach contents of M. merluccius sampled in the North-Central Adriatic Sea were analyzed with both the metabarcoding and morphological approaches. Metabarcoding clearly outperformed the morphological method in the taxonomic identification of prey describing more complex trophic relationships even when considering the morphological identification of 200 stomach contents. Statistical analysis of diet composition revealed a weak differentiation among the hake's size classes, confirming an opportunistic feeding behavior. All the analyses performed showed the presence of a core of shared prey among the size classes and a cloud of size-specific prey. Our study highlights the exceptional potential of metabarcoding as an approach to provide unprecedented taxonomic resolution in the diet of M. merluccius and potentially of other marine predators, due to the broad-spectrum of detection of the primers used. A thorough description of these complex trophic relationships is fundamental for the implementation of an ecosystem approach to fisheries.}, } @article {pmid30464815, year = {2018}, author = {Asbridge, E and Lucas, R and Rogers, K and Accad, A}, title = {The extent of mangrove change and potential for recovery following severe Tropical Cyclone Yasi, Hinchinbrook Island, Queensland, Australia.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10416-10434}, pmid = {30464815}, issn = {2045-7758}, abstract = {Cyclones are significant drivers of change within mangrove ecosystems with the extent of initial damage determined by storm severity, location and distribution (exposure), and influenced by species composition and structure (e.g., height). The long-term recovery of mangroves is often dependent upon hydrological regimes, as well as the frequency of storm events. On February 3, 2011, Tropical Cyclone Yasi (Category 5) made landfall on the coast of north Queensland Australia with its path crossing the extensive mangroves within and surrounding Hinchinbrook Island National Park. Based on a combination of Landsat-derived foliage projective cover (FPC), Queensland Globe aerial imagery, and RapidEye imagery, 16% of the 13,795 ha of mangroves experienced severe windthrow during the storm. The greatest damage from the cyclone was inflicted on mangrove forests dominated primarily by Rhizophora stylosa, whose large prop roots were unable to support them as wind speeds exceeded 280 km/hr. Classification of 2016 RapidEye data indicated that many areas of damage had experienced no or very limited recovery in the period following the cyclone, with this confirmed by a rapid decline in Landsat-derived FPC (from levels > 90% from 1986 to just prior to the cyclone to < 20% postcyclone) and no noticeable increase in subsequent years. Advanced Land Observing Satellite (ALOS-1) Phased Arrayed L-band Synthetic Aperture Radar (SAR) L-band HH backscatter also increased initially and rapidly to 5 ± 2 dB (2007-2011) due to the increase in woody debris but then decreased subsequently to -20 ± 2 dB (postcyclone), as this decomposed or was removed. The lack of recovery in affected areas was attributed to the inability of mangrove species, particularly R. stylosa, to resprout from remaining plant material and persistent inundation due to a decrease in sediment elevation thereby preventing propagule establishment. This study indicates that increases in storm intensity predicted with changes in global climate may lead to a reduction in the area, diversity, and abundance of mangroves surrounding Hinchinbrook Island.}, } @article {pmid30464814, year = {2018}, author = {Walsh, JT and Signorotti, L and Linksvayer, TA and d'Ettorre, P}, title = {Phenotypic correlation between queen and worker brood care supports the role of maternal care in the evolution of eusociality.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10409-10415}, pmid = {30464814}, issn = {2045-7758}, abstract = {Cooperative brood care by siblings, a defining feature of eusociality, is hypothesized to be evolutionarily derived from maternal care via shifts in the timing of the expression of genes underlying maternal care. If sibling and maternal care share a genetic basis, the two behaviors are expected to be genetically and phenotypically correlated. We tested this prediction in the black garden ant Lasius niger by quantifying the brood retrieval rate of queens and their first and later generation worker offspring. Brood retrieval rate of queens was positively phenotypically correlated with the brood retrieval rate of first generation but not with later generation workers. The difference between first and later generation workers could be due to the stronger similarity in care behavior provided by queens and first generation workers compared to later generations. Furthermore, we found that queen retrieval rate was positively correlated with colony productivity, suggesting that natural selection is acting on maternal care. Overall, our results support the idea of a shared genetic basis between maternal and sibling care as well as queen and worker traits more generally, which has implications for the role of intercaste correlations in the evolution of queen and worker traits and eusociality.}, } @article {pmid30464813, year = {2018}, author = {Maure, LA and Rodrigues, RC and Alcântara, ÂV and Adorno, BFCB and Santos, DL and Abreu, EL and Tanaka, RM and Gonçalves, RM and Hasui, E}, title = {Functional Redundancy in bird community decreases with riparian forest width reduction.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10395-10408}, pmid = {30464813}, issn = {2045-7758}, abstract = {Riparian ecosystems are suffering anthropogenic threats that reduce biodiversity and undermine ecosystem services. However, there is a great deal of uncertainty about the way species composition of assemblages is related to ecosystem function, especially in a landscape fragmentation context.Here, we assess the impact of habitat loss and disturbance on Functional Diversity (FD) components Functional Redundancy (FRed), Functional Evenness (FEve), and Functional Richness (FRic) of riparian forest bird assemblages to evaluate (a) how FD components respond to riparian forest width reduction and vegetation disturbance; (b) the existence of thresholds within these relationships; (c) which of the main birds diet guild (frugivores, insectivores, and omnivores) respond to such thresholds. We predict that FD components will be affected negatively and nonlinearly by riparian changes. However, guilds could have different responses due to differences of species sensitivity to fragmentation and disturbance. We expect to find thresholds in FD responses, because fragmentation and disturbance drive loss of specific FD components.Our results show that FRed and FEve were linearly affected by width and disturbance of riparian habitats, respectively. FRed was significantly lower in riparian forests assemblages below 400 m wide, and FEve was significantly higher above 60% disturbance. These responses of FD were also followed to the decline in insectivores and frugivores richness in riparian forests most affected by these changes.Consequently, our study suggests communities do not tolerate reduction in riparian forest width or disturbance intensification without negative impact on FD, and this becomes more critical for riparian area <400-m wide or with more than 60% disturbance. This minimum riparian width required to maintain FRed is greater than the minimum width required for riparian forests by Brazilian law. Thus, it is important to consider mechanisms to expand riparian habitats and reduce the disturbance intensity in riparian forests so that riparian bird community FD may be effectively conserved.}, } @article {pmid30464812, year = {2018}, author = {Revynthi, AM and Egas, M and Janssen, A and Sabelis, MW}, title = {Prey exploitation and dispersal strategies vary among natural populations of a predatory mite.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10384-10394}, pmid = {30464812}, issn = {2045-7758}, abstract = {When predators commonly overexploit local prey populations, dispersal drives the dynamics in local patches, which together form a metapopulation. Two extremes in a continuum of dispersal strategies are distinguished: the "Killer" strategy, where predators only start dispersing when all prey are eliminated, and the "Milker" strategy, in which predator dispersal occurs irrespective of prey availability. Theory shows that the Milker strategy is not evolutionarily stable if local populations are well connected by dispersal. Using strains of the predatory mite Phytoseiulus persimilis, collected from 11 native populations from coastal areas in Turkey and Sicily, we investigated whether these two strategies occur in nature. In small wind tunnels, we measured dispersal rates and population dynamics of all populations in a system consisting of detached rose leaves, spider mites (Tetranychus urticae) as prey, and P. persimilis. We found significant variation in the exploitation and dispersal strategies among predator populations, but none of the collected strains showed the extreme Killer or Milker strategy. The results suggest that there is genetic variation for prey exploitation and dispersal strategies. Thus, different dispersal strategies in the Milker-Killer continuum may be selected for under natural conditions. This may affect the predator-prey dynamics in local populations and is likely to determine persistence of predator-prey systems at the metapopulation level.}, } @article {pmid30464811, year = {2018}, author = {Rolandi, C and Lighton, JRB and de la Vega, GJ and Schilman, PE and Mensch, J}, title = {Genetic variation for tolerance to high temperatures in a population of Drosophila melanogaster.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10374-10383}, pmid = {30464811}, issn = {2045-7758}, abstract = {The range of thermal tolerance is one of the main factors influencing the geographic distribution of species. Climate change projections predict increases in average and extreme temperatures over the coming decades; hence, the ability of living beings to resist these changes will depend on physiological and adaptive responses. On an evolutionary scale, changes will occur as the result of selective pressures on individual heritable differences. In this work, we studied the genetic basis of tolerance to high temperatures in the fly Drosophila melanogaster and whether this species presents sufficient genetic variability to allow expansion of its upper thermo-tolerance limit. To do so, we used adult flies derived from a natural population belonging to the Drosophila Genetic Reference Panel, for which genomic sequencing data are available. We characterized the phenotypic variation of the upper thermal limit in 34 lines by measuring knockdown temperature (i.e., critical thermal maximum [CTmax]) by exposing flies to a ramp of increasing temperature (0.25°C/min). Fourteen percent of the variation in CTmax is explained by the genetic variation across lines, without a significant sexual dimorphism. Through a genomewide association study, 12 single nucleotide polymorphisms associated with the CTmax were identified. In most of these SNPs, the less frequent allele increased the upper thermal limit suggesting that this population harbors raw genetic variation capable of expanding its heat tolerance. This potential upper thermal tolerance increase has implications under the global warming scenario. Past climatic records show a very low incidence of days above CTmax (10 days over 25 years); however, future climate scenarios predict 243 days with extreme high temperature above CTmax from 2045 to 2070. Thus, in the context of the future climate warming, rising temperatures might drive the evolution of heat tolerance in this population by increasing the frequency of the alleles associated with higher CTmax.}, } @article {pmid30464810, year = {2018}, author = {Pashirzad, M and Ejtehadi, H and Vaezi, J and Shefferson, RP}, title = {Spatial scale-dependent phylogenetic signal in species distributions along geographic and elevation gradients in a mountainous rangeland.}, journal = {Ecology and evolution}, volume = {8}, number = {21}, pages = {10364-10373}, pmid = {30464810}, issn = {2045-7758}, abstract = {The mechanisms determining community phylogenetic structure range from local ecological mechanisms to broad biogeographical processes. How these community assembly processes determine phylogenetic structure and patterns in rangeland communities across multiple spatial scales is still poorly understood. We sought to determine whether the structure of herbaceous and shrub assemblages along local environmental gradients (elevation) and broad geography (latitude) exhibited phylogenetic signal at different spatial scales, across 2,500 ha of a mountainous rangeland. We analyzed species distribution and phylogenetic data at two spatial scales: the community level (1 m2 sample units obtained by stratified random sampling) and the habitat level (plant assemblages identified categorically based on environmental and geographical variables). We found significant phylogenetic signal in structure and pattern at both spatial scales, along local elevational, and latitudinal gradients. Moreover, beta diversity was affected by different environmental variables in herbaceous and shrub species distributions across different spatial scales. Our results highlight the relative importance of local ecological mechanisms, including niche-based deterministic processes (environmental filtering and species interactions) as well as those of biogeographical processes, such as stochastic dispersal limitation and habitat specialization in plant assemblages of mountainous rangeland.}, } @article {pmid30464354, year = {2018}, author = {Lidgard, S and Love, AC}, title = {Corrigendum: Rethinking Living Fossils.}, journal = {Bioscience}, volume = {68}, number = {11}, pages = {926}, doi = {10.1093/biosci/biy129}, pmid = {30464354}, issn = {0006-3568}, abstract = {[This corrects the article DOI: 10.1093/biosci/biy084.].}, } @article {pmid30464353, year = {2018}, author = {Januchowski-Hartley, SR and Sopinka, N and Merkle, BG and Lux, C and Zivian, A and Goff, P and Oester, S}, title = {Poetry as a Creative Practice to Enhance Engagement and Learning in Conservation Science.}, journal = {Bioscience}, volume = {68}, number = {11}, pages = {905-911}, pmid = {30464353}, issn = {0006-3568}, abstract = {Creativity is crucial to the capacity to do science well, to communicate it in compelling ways, and to enhance learning. Creativity can be both practiced and enhanced to strengthen conservation science professionals' efforts to address global environmental challenges. We explore how poetry is one creative approach that can further conservation scientists' engagement and learning. We draw on evidence from peer-reviewed literature to illustrate benefits of integrating science and poetry, and to ground our argument for the growth of a science-poetry community to help conservation scientists develop skills in creative practices as a component of professional development. We present examples from literature as well as two short poetry exercises for scientists to draw on when considering writing poetry, or deciding on forms of poetry to include, in their practice. Opportunity exists to grow science-poetry projects to further our understanding of what such initiatives can offer.}, } @article {pmid30464352, year = {2018}, author = {Waldock, C and Dornelas, M and Bates, AE}, title = {Temperature-Driven Biodiversity Change: Disentangling Space and Time.}, journal = {Bioscience}, volume = {68}, number = {11}, pages = {873-884}, pmid = {30464352}, issn = {0006-3568}, abstract = {Temperature regimes have multiple spatial and temporal dimensions that have different impacts on biodiversity. Signatures of warming across these dimensions may contribute uniquely to the large-scale species redistributions and abundance changes that underpin community dynamics. A comprehensive review of the literature reveals that 86% of studies were focused on community responses to temperature aggregated over spatial or temporal dimensions (e.g., mean, median, or extremes). Therefore, the effects of temperature variation in space and time on biodiversity remain generally unquantified. In the present article, we argue that this focus on aggregated temperature measures may limit advancing our understanding of how communities are being altered by climate change. In light of this, we map the cause-and-effect pathways between the different dimensions of temperature change and communities in space and time. A broadened focus, shifted toward a multidimensional perspective of temperature, will allow better interpretation and prediction of biodiversity change and more robust management and conservation strategies.}, } @article {pmid30464351, year = {2018}, author = {Powell, JR and Gloria-Soria, A and Kotsakiozi, P}, title = {Recent History of Aedes aegypti: Vector Genomics and Epidemiology Records.}, journal = {Bioscience}, volume = {68}, number = {11}, pages = {854-860}, pmid = {30464351}, issn = {0006-3568}, support = {U01 AI115595/AI/NIAID NIH HHS/United States ; }, abstract = {Aedes aegypti bears the common name "the yellow fever mosquito," although, today, it is of more concern as the major vector of dengue, chikungunya, and, most recently, Zika viruses. In the present article, we review recent work on the population genetics of this mosquito in efforts to reconstruct its recent (approximately 600 years) history and relate these findings to epidemiological records of occurrences of diseases transmitted by this species. The two sources of information are remarkably congruent. Ae. aegypti was introduced to the New World 400-550 years ago from its ancestral home in West Africa via European slave trade. Ships from the New World returning to their European ports of origin introduced the species to the Mediterranean region around 1800, where it became established until about 1950. The Suez Canal opened in 1869 and Ae. aegypti was introduced into Asia by the 1870s, then on to Australia (1887) and the South Pacific (1904).}, } @article {pmid30464348, year = {2019}, author = {Pickering, R and Herries, AIR and Woodhead, JD and Hellstrom, JC and Green, HE and Paul, B and Ritzman, T and Strait, DS and Schoville, BJ and Hancox, PJ}, title = {U-Pb-dated flowstones restrict South African early hominin record to dry climate phases.}, journal = {Nature}, volume = {565}, number = {7738}, pages = {226-229}, doi = {10.1038/s41586-018-0711-0}, pmid = {30464348}, issn = {1476-4687}, abstract = {The Cradle of Humankind (Cradle) in South Africa preserves a rich collection of fossil hominins representing Australopithecus, Paranthropus and Homo1. The ages of these fossils are contentious2-4 and have compromised the degree to which the South African hominin record can be used to test hypotheses of human evolution. However, uranium-lead (U-Pb) analyses of horizontally bedded layers of calcium carbonate (flowstone) provide a potential opportunity to obtain a robust chronology5. Flowstones are ubiquitous cave features and provide a palaeoclimatic context, because they grow only during phases of increased effective precipitation6,7, ideally in closed caves. Here we show that flowstones from eight Cradle caves date to six narrow time intervals between 3.2 and 1.3 million years ago. We use a kernel density estimate to combine 29 U-Pb ages into a single record of flowstone growth intervals. We interpret these as major wet phases, when an increased water supply, more extensive vegetation cover and at least partially closed caves allowed for undisturbed, semi-continuous growth of the flowstones. The intervening times represent substantially drier phases, during which fossils of hominins and other fossils accumulated in open caves. Fossil preservation, restricted to drier intervals, thus biases the view of hominin evolutionary history and behaviour, and places the hominins in a community of comparatively dry-adapted fauna. Although the periods of cave closure leave temporal gaps in the South African fossil record, the flowstones themselves provide valuable insights into both local and pan-African climate variability.}, } @article {pmid30464347, year = {2018}, author = {Marlétaz, F and Firbas, PN and Maeso, I and Tena, JJ and Bogdanovic, O and Perry, M and Wyatt, CDR and de la Calle-Mustienes, E and Bertrand, S and Burguera, D and Acemel, RD and van Heeringen, SJ and Naranjo, S and Herrera-Ubeda, C and Skvortsova, K and Jimenez-Gancedo, S and Aldea, D and Marquez, Y and Buono, L and Kozmikova, I and Permanyer, J and Louis, A and Albuixech-Crespo, B and Le Petillon, Y and Leon, A and Subirana, L and Balwierz, PJ and Duckett, PE and Farahani, E and Aury, JM and Mangenot, S and Wincker, P and Albalat, R and Benito-Gutiérrez, È and Cañestro, C and Castro, F and D'Aniello, S and Ferrier, DEK and Huang, S and Laudet, V and Marais, GAB and Pontarotti, P and Schubert, M and Seitz, H and Somorjai, I and Takahashi, T and Mirabeau, O and Xu, A and Yu, JK and Carninci, P and Martinez-Morales, JR and Crollius, HR and Kozmik, Z and Weirauch, MT and Garcia-Fernàndez, J and Lister, R and Lenhard, B and Holland, PWH and Escriva, H and Gómez-Skarmeta, JL and Irimia, M}, title = {Amphioxus functional genomics and the origins of vertebrate gene regulation.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {64-70}, pmid = {30464347}, issn = {1476-4687}, abstract = {Vertebrates have greatly elaborated the basic chordate body plan and evolved highly distinctive genomes that have been sculpted by two whole-genome duplications. Here we sequence the genome of the Mediterranean amphioxus (Branchiostoma lanceolatum) and characterize DNA methylation, chromatin accessibility, histone modifications and transcriptomes across multiple developmental stages and adult tissues to investigate the evolution of the regulation of the chordate genome. Comparisons with vertebrates identify an intermediate stage in the evolution of differentially methylated enhancers, and a high conservation of gene expression and its cis-regulatory logic between amphioxus and vertebrates that occurs maximally at an earlier mid-embryonic phylotypic period. We analyse regulatory evolution after whole-genome duplications, and find that-in vertebrates-over 80% of broadly expressed gene families with multiple paralogues derived from whole-genome duplications have members that restricted their ancestral expression, and underwent specialization rather than subfunctionalization. Counter-intuitively, paralogues that restricted their expression increased the complexity of their regulatory landscapes. These data pave the way for a better understanding of the regulatory principles that underlie key vertebrate innovations.}, } @article {pmid30464346, year = {2018}, author = {van Breugel, F and Huda, A and Dickinson, MH}, title = {Distinct activity-gated pathways mediate attraction and aversion to CO2 in Drosophila.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {420-424}, doi = {10.1038/s41586-018-0732-8}, pmid = {30464346}, issn = {1476-4687}, support = {U01 NS090514/NS/NINDS NIH HHS/United States ; U19 NS104655/NS/NINDS NIH HHS/United States ; NIH1RO1DCO13693-01/DC/NIDCD NIH HHS/United States ; }, abstract = {Carbon dioxide is produced by many organic processes and is a convenient volatile cue for insects1 that are searching for blood hosts2, flowers3, communal nests4, fruit5 and wildfires6. Although Drosophila melanogaster feed on yeast that produce CO2 and ethanol during fermentation, laboratory experiments7-12 suggest that walking flies avoid CO2. Here we resolve this paradox by showing that both flying and walking Drosophila find CO2 attractive, but only when they are in an active state associated with foraging. Their aversion to CO2 at low-activity levels may be an adaptation to avoid parasites that seek CO2, or to avoid succumbing to respiratory acidosis in the presence of high concentrations of CO2 that exist in nature13,14. In contrast to CO2, flies are attracted to ethanol in all behavioural states, and invest twice the time searching near ethanol compared to CO2. These behavioural differences reflect the fact that ethanol is a unique signature of yeast fermentation, whereas CO2 is generated by many natural processes. Using genetic tools, we determined that the evolutionarily conserved ionotropic co-receptor IR25a is required for CO2 attraction, and that the receptors necessary for CO2 avoidance are not involved in this attraction. Our study lays the foundation for future research to determine the neural circuits that underlie both state- and odorant-dependent decision-making in Drosophila.}, } @article {pmid30464345, year = {2018}, author = {Chessum, L and Matern, MS and Kelly, MC and Johnson, SL and Ogawa, Y and Milon, B and McMurray, M and Driver, EC and Parker, A and Song, Y and Codner, G and Esapa, CT and Prescott, J and Trent, G and Wells, S and Dragich, AK and Frolenkov, GI and Kelley, MW and Marcotti, W and Brown, SDM and Elkon, R and Bowl, MR and Hertzano, R}, title = {Helios is a key transcriptional regulator of outer hair cell maturation.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {696-700}, doi = {10.1038/s41586-018-0728-4}, pmid = {30464345}, issn = {1476-4687}, support = {NIH T32DC00046/DC/NIDCD NIH HHS/United States ; R01 DC003544/DC/NIDCD NIH HHS/United States ; F31 DC016218/DC/NIDCD NIH HHS/United States ; R01 DC014658/DC/NIDCD NIH HHS/United States ; R01 DC013817/DC/NIDCD NIH HHS/United States ; MC_U142684175//Medical Research Council/United Kingdom ; NIDCD DC000059/DC/NIDCD NIH HHS/United States ; T32 DC000046/DC/NIDCD NIH HHS/United States ; }, abstract = {The sensory cells that are responsible for hearing include the cochlear inner hair cells (IHCs) and outer hair cells (OHCs), with the OHCs being necessary for sound sensitivity and tuning1. Both cell types are thought to arise from common progenitors; however, our understanding of the factors that control the fate of IHCs and OHCs remains limited. Here we identify Ikzf2 (which encodes Helios) as an essential transcription factor in mice that is required for OHC functional maturation and hearing. Helios is expressed in postnatal mouse OHCs, and in the cello mouse model a point mutation in Ikzf2 causes early-onset sensorineural hearing loss. Ikzf2cello/cello OHCs have greatly reduced prestin-dependent electromotile activity, a hallmark of OHC functional maturation, and show reduced levels of crucial OHC-expressed genes such as Slc26a5 (which encodes prestin) and Ocm. Moreover, we show that ectopic expression of Ikzf2 in IHCs: induces the expression of OHC-specific genes; reduces the expression of canonical IHC genes; and confers electromotility to IHCs, demonstrating that Ikzf2 can partially shift the IHC transcriptome towards an OHC-like identity.}, } @article {pmid30464344, year = {2018}, author = {Shabek, N and Ticchiarelli, F and Mao, H and Hinds, TR and Leyser, O and Zheng, N}, title = {Structural plasticity of D3-D14 ubiquitin ligase in strigolactone signalling.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {652-656}, pmid = {30464344}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {The strigolactones, a class of plant hormones, regulate many aspects of plant physiology. In the inhibition of shoot branching, the α/β hydrolase D14-which metabolizes strigolactone-interacts with the F-box protein D3 to ubiquitinate and degrade the transcription repressor D53. Despite the fact that multiple modes of interaction between D14 and strigolactone have recently been determined, how the hydrolase functions with D3 to mediate hormone-dependent D53 ubiquitination remains unknown. Here we show that D3 has a C-terminal α-helix that can switch between two conformational states. The engaged form of this α-helix facilitates the binding of D3 and D14 with a hydrolysed strigolactone intermediate, whereas the dislodged form can recognize unmodified D14 in an open conformation and inhibits its enzymatic activity. The D3 C-terminal α-helix enables D14 to recruit D53 in a strigolactone-dependent manner, which in turn activates the hydrolase. By revealing the structural plasticity of the SCFD3-D14 ubiquitin ligase, our results suggest a mechanism by which the E3 coordinates strigolactone signalling and metabolism.}, } @article {pmid30464343, year = {2018}, author = {Morioka, S and Perry, JSA and Raymond, MH and Medina, CB and Zhu, Y and Zhao, L and Serbulea, V and Onengut-Gumuscu, S and Leitinger, N and Kucenas, S and Rathmell, JC and Makowski, L and Ravichandran, KS}, title = {Efferocytosis induces a novel SLC program to promote glucose uptake and lactate release.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {714-718}, doi = {10.1038/s41586-018-0735-5}, pmid = {30464343}, issn = {1476-4687}, support = {P01 HL120840/HL/NHLBI NIH HHS/United States ; R01 GM064709/GM/NIGMS NIH HHS/United States ; R01 NS072212/NS/NINDS NIH HHS/United States ; R35 GM122542/GM/NIGMS NIH HHS/United States ; }, abstract = {Development and routine tissue homeostasis require a high turnover of apoptotic cells. These cells are removed by professional and non-professional phagocytes via efferocytosis1. How a phagocyte maintains its homeostasis while coordinating corpse uptake, processing ingested materials and secreting anti-inflammatory mediators is incompletely understood1,2. Here, using RNA sequencing to characterize the transcriptional program of phagocytes actively engulfing apoptotic cells, we identify a genetic signature involving 33 members of the solute carrier (SLC) family of membrane transport proteins, in which expression is specifically modulated during efferocytosis, but not during antibody-mediated phagocytosis. We assessed the functional relevance of these SLCs in efferocytic phagocytes and observed a robust induction of an aerobic glycolysis program, initiated by SLC2A1-mediated glucose uptake, with concurrent suppression of the oxidative phosphorylation program. The different steps of phagocytosis2-that is, 'smell' ('find-me' signals or sensing factors released by apoptotic cells), 'taste' (phagocyte-apoptotic cell contact) and 'ingestion' (corpse internalization)-activated distinct and overlapping sets of genes, including several SLC genes, to promote glycolysis. SLC16A1 was upregulated after corpse uptake, increasing the release of lactate, a natural by-product of aerobic glycolysis3. Whereas glycolysis within phagocytes contributed to actin polymerization and the continued uptake of corpses, lactate released via SLC16A1 promoted the establishment of an anti-inflammatory tissue environment. Collectively, these data reveal a SLC program that is activated during efferocytosis, identify a previously unknown reliance on aerobic glycolysis during apoptotic cell uptake and show that glycolytic by-products of efferocytosis can influence surrounding cells.}, } @article {pmid30464342, year = {2018}, author = {Gerlach, D and Guo, Y and De Castro, C and Kim, SH and Schlatterer, K and Xu, FF and Pereira, C and Seeberger, PH and Ali, S and Codée, J and Sirisarn, W and Schulte, B and Wolz, C and Larsen, J and Molinaro, A and Lee, BL and Xia, G and Stehle, T and Peschel, A}, title = {Methicillin-resistant Staphylococcus aureus alters cell wall glycosylation to evade immunity.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {705-709}, doi = {10.1038/s41586-018-0730-x}, pmid = {30464342}, issn = {1476-4687}, abstract = {Methicillin-resistant Staphylococcus aureus (MRSA) is a frequent cause of difficult-to-treat, often fatal infections in humans1,2. Most humans have antibodies against S. aureus, but these are highly variable and often not protective in immunocompromised patients3. Previous vaccine development programs have not been successful4. A large percentage of human antibodies against S. aureus target wall teichoic acid (WTA), a ribitol-phosphate (RboP) surface polymer modified with N-acetylglucosamine (GlcNAc)5,6. It is currently unknown whether the immune evasion capacities of MRSA are due to variation of dominant surface epitopes such as those associated with WTA. Here we show that a considerable proportion of the prominent healthcare-associated and livestock-associated MRSA clones CC5 and CC398, respectively, contain prophages that encode an alternative WTA glycosyltransferase. This enzyme, TarP, transfers GlcNAc to a different hydroxyl group of the WTA RboP than the standard enzyme TarS7, with important consequences for immune recognition. TarP-glycosylated WTA elicits 7.5-40-fold lower levels of immunoglobulin G in mice than TarS-modified WTA. Consistent with this, human sera contained only low levels of antibodies against TarP-modified WTA. Notably, mice immunized with TarS-modified WTA were not protected against infection with tarP-expressing MRSA, indicating that TarP is crucial for the capacity of S. aureus to evade host defences. High-resolution structural analyses of TarP bound to WTA components and uridine diphosphate GlcNAc (UDP-GlcNAc) explain the mechanism of altered RboP glycosylation and form a template for targeted inhibition of TarP. Our study reveals an immune evasion strategy of S. aureus based on averting the immunogenicity of its dominant glycoantigen WTA. These results will help with the identification of invariant S. aureus vaccine antigens and may enable the development of TarP inhibitors as a new strategy for rendering MRSA susceptible to human host defences.}, } @article {pmid30464341, year = {2018}, author = {Gonzalez, PS and O'Prey, J and Cardaci, S and Barthet, VJA and Sakamaki, JI and Beaumatin, F and Roseweir, A and Gay, DM and Mackay, G and Malviya, G and Kania, E and Ritchie, S and Baudot, AD and Zunino, B and Mrowinska, A and Nixon, C and Ennis, D and Hoyle, A and Millan, D and McNeish, IA and Sansom, OJ and Edwards, J and Ryan, KM}, title = {Mannose impairs tumour growth and enhances chemotherapy.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {719-723}, doi = {10.1038/s41586-018-0729-3}, pmid = {30464341}, issn = {1476-4687}, abstract = {It is now well established that tumours undergo changes in cellular metabolism1. As this can reveal tumour cell vulnerabilities and because many tumours exhibit enhanced glucose uptake2, we have been interested in how tumour cells respond to different forms of sugar. Here we report that the monosaccharide mannose causes growth retardation in several tumour types in vitro, and enhances cell death in response to major forms of chemotherapy. We then show that these effects also occur in vivo in mice following the oral administration of mannose, without significantly affecting the weight and health of the animals. Mechanistically, mannose is taken up by the same transporter(s) as glucose3 but accumulates as mannose-6-phosphate in cells, and this impairs the further metabolism of glucose in glycolysis, the tricarboxylic acid cycle, the pentose phosphate pathway and glycan synthesis. As a result, the administration of mannose in combination with conventional chemotherapy affects levels of anti-apoptotic proteins of the Bcl-2 family, leading to sensitization to cell death. Finally we show that susceptibility to mannose is dependent on the levels of phosphomannose isomerase (PMI). Cells with low levels of PMI are sensitive to mannose, whereas cells with high levels are resistant, but can be made sensitive by RNA-interference-mediated depletion of the enzyme. In addition, we use tissue microarrays to show that PMI levels also vary greatly between different patients and different tumour types, indicating that PMI levels could be used as a biomarker to direct the successful administration of mannose. We consider that the administration of mannose could be a simple, safe and selective therapy in the treatment of cancer, and could be applicable to multiple tumour types.}, } @article {pmid30464340, year = {2018}, author = {Chu, Y and Kharel, P and Yoon, T and Frunzio, L and Rakich, PT and Schoelkopf, RJ}, title = {Creation and control of multi-phonon Fock states in a bulk acoustic-wave resonator.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {666-670}, doi = {10.1038/s41586-018-0717-7}, pmid = {30464340}, issn = {1476-4687}, abstract = {Quantum states of mechanical motion can be important resources for quantum information, metrology and studies of fundamental physics. Recent demonstrations of superconducting qubits coupled to acoustic resonators have opened up the possibility of performing quantum operations on macroscale motional modes1-3, which can act as long-lived quantum memories or transducers. In addition, they can potentially be used to test decoherence mechanisms in macroscale objects and other modifications to standard quantum theory4,5. Many of these applications call for the ability to create and characterize complex quantum states, such as states with a well defined phonon number, also known as phonon Fock states. Such capabilities require fast quantum operations and long coherence times of the mechanical mode. Here we demonstrate the controlled generation of multi-phonon Fock states in a macroscale bulk acoustic-wave resonator. We also perform Wigner tomography and state reconstruction to highlight the quantum nature of the prepared states6. These demonstrations are made possible by the long coherence times of our acoustic resonator and our ability to selectively couple a superconducting qubit to individual phonon modes. Our work shows that circuit quantum acoustodynamics7 enables sophisticated quantum control of macroscale mechanical objects and opens up the possibility of using acoustic modes as quantum resources.}, } @article {pmid30464339, year = {2018}, author = {Satzinger, KJ and Zhong, YP and Chang, HS and Peairs, GA and Bienfait, A and Chou, MH and Cleland, AY and Conner, CR and Dumur, É and Grebel, J and Gutierrez, I and November, BH and Povey, RG and Whiteley, SJ and Awschalom, DD and Schuster, DI and Cleland, AN}, title = {Quantum control of surface acoustic-wave phonons.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {661-665}, doi = {10.1038/s41586-018-0719-5}, pmid = {30464339}, issn = {1476-4687}, abstract = {One of the hallmarks of quantum physics is the generation of non-classical quantum states and superpositions, which has been demonstrated in several quantum systems, including ions, solid-state qubits and photons. However, only indirect demonstrations of non-classical states have been achieved in mechanical systems, despite the scientific appeal and technical utility of such a capability1,2, including in quantum sensing, computation and communication applications. This is due in part to the highly linear response of most mechanical systems, which makes quantum operations difficult, as well as their characteristically low frequencies, which hinder access to the quantum ground state3-7. Here we demonstrate full quantum control of the mechanical state of a macroscale mechanical resonator. We strongly couple a surface acoustic-wave8 resonator to a superconducting qubit, using the qubit to control and measure quantum states in the mechanical resonator. We generate a non-classical superposition of the zero- and one-phonon Fock states and map this and other states using Wigner tomography9-14. Such precise, programmable quantum control is essential to a range of applications of surface acoustic waves in the quantum limit, including the coupling of disparate quantum systems15,16.}, } @article {pmid30464338, year = {2018}, author = {Lee, MH and Siddoway, B and Kaeser, GE and Segota, I and Rivera, R and Romanow, WJ and Liu, CS and Park, C and Kennedy, G and Long, T and Chun, J}, title = {Somatic APP gene recombination in Alzheimer's disease and normal neurons.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {639-645}, doi = {10.1038/s41586-018-0718-6}, pmid = {30464338}, issn = {1476-4687}, support = {P50 AG005131/AG/NIA NIH HHS/United States ; T32 AG000216/AG/NIA NIH HHS/United States ; }, abstract = {The diversity and complexity of the human brain are widely assumed to be encoded within a constant genome. Somatic gene recombination, which changes germline DNA sequences to increase molecular diversity, could theoretically alter this code but has not been documented in the brain, to our knowledge. Here we describe recombination of the Alzheimer's disease-related gene APP, which encodes amyloid precursor protein, in human neurons, occurring mosaically as thousands of variant 'genomic cDNAs' (gencDNAs). gencDNAs lacked introns and ranged from full-length cDNA copies of expressed, brain-specific RNA splice variants to myriad smaller forms that contained intra-exonic junctions, insertions, deletions, and/or single nucleotide variations. DNA in situ hybridization identified gencDNAs within single neurons that were distinct from wild-type loci and absent from non-neuronal cells. Mechanistic studies supported neuronal 'retro-insertion' of RNA to produce gencDNAs; this process involved transcription, DNA breaks, reverse transcriptase activity, and age. Neurons from individuals with sporadic Alzheimer's disease showed increased gencDNA diversity, including eleven mutations known to be associated with familial Alzheimer's disease that were absent from healthy neurons. Neuronal gene recombination may allow 'recording' of neural activity for selective 'playback' of preferred gene variants whose expression bypasses splicing; this has implications for cellular diversity, learning and memory, plasticity, and diseases of the human brain.}, } @article {pmid30464337, year = {2018}, author = {Chen, YL and Chen, LJ and Chu, CC and Huang, PK and Wen, JR and Li, HM}, title = {TIC236 links the outer and inner membrane translocons of the chloroplast.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {125-129}, doi = {10.1038/s41586-018-0713-y}, pmid = {30464337}, issn = {1476-4687}, abstract = {The two-membrane envelope is a defining feature of chloroplasts. Chloroplasts evolved from a Gram-negative cyanobacterial endosymbiont. During evolution, genes of the endosymbiont have been transferred to the host nuclear genome. Most chloroplast proteins are synthesized in the cytosol as higher-molecular-mass preproteins with an N-terminal transit peptide. Preproteins are transported into chloroplasts by the TOC and TIC (translocons at the outer- and inner-envelope membranes of chloroplasts, respectively) machineries1,2, but how TOC and TIC are assembled together is unknown. Here we report the identification of the TIC component TIC236; TIC236 is an integral inner-membrane protein that projects a 230-kDa domain into the intermembrane space, which binds directly to the outer-membrane channel TOC75. The knockout mutation of TIC236 is embryonically lethal. In TIC236-knockdown mutants, a smaller amount of the inner-membrane channel TIC20 was associated with TOC75; the amount of TOC-TIC supercomplexes was also reduced. This resulted in a reduced import rate into the stroma, though outer-membrane protein insertion was unaffected. The size and the essential nature of TIC236 indicate that-unlike in mitochondria, in which the outer- and inner-membrane translocons exist as separate complexes and a supercomplex is only transiently assembled during preprotein translocation3,4-a long and stable protein bridge in the intermembrane space is required for protein translocation into chloroplasts. Furthermore, TIC236 and TOC75 are homologues of bacterial inner-membrane TamB5 and outer-membrane BamA, respectively. Our evolutionary analyses show that, similar to TOC75, TIC236 is preserved only in plants and has co-evolved with TOC75 throughout the plant lineage. This suggests that the backbone of the chloroplast protein-import machinery evolved from the bacterial TamB-BamA protein-secretion system.}, } @article {pmid30464289, year = {2018}, author = {Courtland, R}, title = {The microscope revolution that's sweeping through materials science.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {462-464}, doi = {10.1038/d41586-018-07448-0}, pmid = {30464289}, issn = {1476-4687}, } @article {pmid30464288, year = {2018}, author = {Willyard, C}, title = {Unlocking the secrets of scar-free skin healing.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S86-S88}, doi = {10.1038/d41586-018-07430-w}, pmid = {30464288}, issn = {1476-4687}, } @article {pmid30464287, year = {2018}, author = {Gould, J}, title = {Superpowered skin.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S84-S85}, doi = {10.1038/d41586-018-07429-3}, pmid = {30464287}, issn = {1476-4687}, } @article {pmid30464286, year = {2018}, author = {Bourzac, K}, title = {Moving skin beyond the biological.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S96-S98}, doi = {10.1038/d41586-018-07434-6}, pmid = {30464286}, issn = {1476-4687}, } @article {pmid30464285, year = {2018}, author = {DeWeerdt, S}, title = {The edible skincare diet.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S94-S95}, doi = {10.1038/d41586-018-07433-7}, pmid = {30464285}, issn = {1476-4687}, } @article {pmid30464284, year = {2018}, author = {Harris, J}, title = {Vitiligo's impact is in the eye of the beholder.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S99}, doi = {10.1038/d41586-018-07435-5}, pmid = {30464284}, issn = {1476-4687}, } @article {pmid30464283, year = {2018}, author = {Sohn, E}, title = {Skin microbiota's community effort.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S91-S93}, doi = {10.1038/d41586-018-07432-8}, pmid = {30464283}, issn = {1476-4687}, } @article {pmid30464282, year = {2018}, author = {Gravitz, L}, title = {Skin.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S83}, doi = {10.1038/d41586-018-07428-4}, pmid = {30464282}, issn = {1476-4687}, } @article {pmid30464281, year = {2018}, author = {Svoboda, E}, title = {When skin's defence against pollution fails.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {S89-S90}, doi = {10.1038/d41586-018-07431-9}, pmid = {30464281}, issn = {1476-4687}, } @article {pmid30464280, year = {2018}, author = {}, title = {Mars rover, French research integrity and NIPS renamed.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {448-449}, doi = {10.1038/d41586-018-07480-0}, pmid = {30464280}, issn = {1476-4687}, } @article {pmid30464279, year = {2018}, author = {}, title = {Stop exploitation of foreign postdocs in the United States.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {444}, doi = {10.1038/d41586-018-07479-7}, pmid = {30464279}, issn = {1476-4687}, } @article {pmid30464278, year = {2018}, author = {Kusamoto, T and Nishihara, H}, title = {Efficiency breakthrough for radical LEDs.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {480-481}, doi = {10.1038/d41586-018-07394-x}, pmid = {30464278}, issn = {1476-4687}, } @article {pmid30464277, year = {2018}, author = {Plouraboué, F}, title = {Flying with ionic wind.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {476-477}, doi = {10.1038/d41586-018-07411-z}, pmid = {30464277}, issn = {1476-4687}, } @article {pmid30464276, year = {2018}, author = {Tessmer, G}, title = {How it feels to be swallowed by a black hole.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {592}, doi = {10.1038/d41586-018-07441-7}, pmid = {30464276}, issn = {1476-4687}, } @article {pmid30464275, year = {2018}, author = {Kirchhelle, C}, title = {Patchwork regulation won't stop antimicrobial resistance.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {473}, doi = {10.1038/d41586-018-07454-2}, pmid = {30464275}, issn = {1476-4687}, } @article {pmid30464274, year = {2018}, author = {Dena, S and Rebouças, R and Augusto-Alves, G and Toledo, LF}, title = {Lessons from recordings lost in Brazil fire: deposit and back up.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {473}, doi = {10.1038/d41586-018-07456-0}, pmid = {30464274}, issn = {1476-4687}, } @article {pmid30464273, year = {2018}, author = {Aalipour, A}, title = {Lab life - when privileged are a minority, equity stands a chance.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {473}, doi = {10.1038/d41586-018-07453-3}, pmid = {30464273}, issn = {1476-4687}, } @article {pmid30464272, year = {2018}, author = {Maswime, S and Masukume, G and Chandiwana, N}, title = {African clinician scientists - mentors and networks help.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {473}, doi = {10.1038/d41586-018-07455-1}, pmid = {30464272}, issn = {1476-4687}, } @article {pmid30464271, year = {2018}, author = {Gibney, E}, title = {Largest overhaul of scientific units since 1875 wins approval.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {451-452}, doi = {10.1038/d41586-018-07424-8}, pmid = {30464271}, issn = {1476-4687}, } @article {pmid30464270, year = {2018}, author = {Xu, H and He, Y and Strobel, KL and Gilmore, CK and Kelley, SP and Hennick, CC and Sebastian, T and Woolston, MR and Perreault, DJ and Barrett, SRH}, title = {Flight of an aeroplane with solid-state propulsion.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {532-535}, doi = {10.1038/s41586-018-0707-9}, pmid = {30464270}, issn = {1476-4687}, abstract = {Since the first aeroplane flight more than 100 years ago, aeroplanes have been propelled using moving surfaces such as propellers and turbines. Most have been powered by fossil-fuel combustion. Electroaerodynamics, in which electrical forces accelerate ions in a fluid1,2, has been proposed as an alternative method of propelling aeroplanes-without moving parts, nearly silently and without combustion emissions3-6. However, no aeroplane with such a solid-state propulsion system has yet flown. Here we demonstrate that a solid-state propulsion system can sustain powered flight, by designing and flying an electroaerodynamically propelled heavier-than-air aeroplane. We flew a fixed-wing aeroplane with a five-metre wingspan ten times and showed that it achieved steady-level flight. All batteries and power systems, including a specifically developed ultralight high-voltage (40-kilovolt) power converter, were carried on-board. We show that conventionally accepted limitations in thrust-to-power ratio and thrust density4,6,7, which were previously thought to make electroaerodynamics unfeasible as a method of aeroplane propulsion, are surmountable. We provide a proof of concept for electroaerodynamic aeroplane propulsion, opening up possibilities for aircraft and aerodynamic devices that are quieter, mechanically simpler and do not emit combustion emissions.}, } @article {pmid30464269, year = {2018}, author = {Pattison, PM and Tsao, JY and Brainard, GC and Bugbee, B}, title = {LEDs for photons, physiology and food.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {493-500}, doi = {10.1038/s41586-018-0706-x}, pmid = {30464269}, issn = {1476-4687}, abstract = {Lighting based on light-emitting diodes (LEDs) not only is more energy efficient than traditional lighting, but also enables improved performance and control. The colour, intensity and distribution of light can now be controlled with unprecedented precision, enabling light to be used both as a signal for specific physiological responses in humans and plants, and as an efficient fuel for fresh food production. Here we show how a broad and improved understanding of the physiological responses to light will facilitate greater energy savings and provide health and productivity benefits that have not previously been associated with lighting.}, } @article {pmid30464268, year = {2018}, author = {Hod, O and Meyer, E and Zheng, Q and Urbakh, M}, title = {Structural superlubricity and ultralow friction across the length scales.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {485-492}, doi = {10.1038/s41586-018-0704-z}, pmid = {30464268}, issn = {1476-4687}, abstract = {Structural superlubricity, a state of ultralow friction and wear between crystalline surfaces, is a fundamental phenomenon in modern tribology that defines a new approach to lubrication. Early measurements involved nanometre-scale contacts between layered materials, but recent experimental advances have extended its applicability to the micrometre scale. This is an important step towards practical utilization of structural superlubricity in future technological applications, such as durable nano- and micro-electromechanical devices, hard drives, mobile frictionless connectors, and mechanical bearings operating under extreme conditions. Here we provide an overview of the field, including its birth and main achievements, the current state of the art and the challenges to fulfilling its potential.}, } @article {pmid30464267, year = {2018}, author = {Ai, X and Evans, EW and Dong, S and Gillett, AJ and Guo, H and Chen, Y and Hele, TJH and Friend, RH and Li, F}, title = {Efficient radical-based light-emitting diodes with doublet emission.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {536-540}, doi = {10.1038/s41586-018-0695-9}, pmid = {30464267}, issn = {1476-4687}, abstract = {Organic light-emitting diodes (OLEDs)1-5, quantum-dot-based LEDs6-10, perovskite-based LEDs11-13 and micro-LEDs14,15 have been championed to fabricate lightweight and flexible units for next-generation displays and active lighting. Although there are already some high-end commercial products based on OLEDs, costs must decrease whilst maintaining high operational efficiencies for the technology to realise wider impact. Here we demonstrate efficient action of radical-based OLEDs16, whose emission originates from a spin doublet, rather than a singlet or triplet exciton. While the emission process is still spin-allowed in these OLEDs, the efficiency limitations imposed by triplet excitons are circumvented for doublets. Using a luminescent radical emitter, we demonstrate an OLED with maximum external quantum efficiency of 27 per cent at a wavelength of 710 nanometres-the highest reported value for deep-red and infrared LEDs. For a standard closed-shell organic semiconductor, holes and electrons occupy the highest occupied and lowest unoccupied molecular orbitals (HOMOs and LUMOs), respectively, and recombine to form singlet or triplet excitons. Radical emitters have a singly occupied molecular orbital (SOMO) in the ground state, giving an overall spin-1/2 doublet. If-as expected on energetic grounds-both electrons and holes occupy this SOMO level, recombination returns the system to the ground state, giving no light emission. However, in our very efficient OLEDs, we achieve selective hole injection into the HOMO and electron injection to the SOMO to form the fluorescent doublet excited state with near-unity internal quantum efficiency.}, } @article {pmid30464266, year = {2018}, author = {Jangra, RK and Herbert, AS and Li, R and Jae, LT and Kleinfelter, LM and Slough, MM and Barker, SL and Guardado-Calvo, P and Román-Sosa, G and Dieterle, ME and Kuehne, AI and Muena, NA and Wirchnianski, AS and Nyakatura, EK and Fels, JM and Ng, M and Mittler, E and Pan, J and Bharrhan, S and Wec, AZ and Lai, JR and Sidhu, SS and Tischler, ND and Rey, FA and Moffat, J and Brummelkamp, TR and Wang, Z and Dye, JM and Chandran, K}, title = {Protocadherin-1 is essential for cell entry by New World hantaviruses.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {559-563}, doi = {10.1038/s41586-018-0702-1}, pmid = {30464266}, issn = {1476-4687}, abstract = {The zoonotic transmission of hantaviruses from their rodent hosts to humans in North and South America is associated with a severe and frequently fatal respiratory disease, hantavirus pulmonary syndrome (HPS)1,2. No specific antiviral treatments for HPS are available, and no molecular determinants of in vivo susceptibility to hantavirus infection and HPS are known. Here we identify the human asthma-associated gene protocadherin-1 (PCDH1)3-6 as an essential determinant of entry and infection in pulmonary endothelial cells by two hantaviruses that cause HPS, Andes virus (ANDV) and Sin Nombre virus (SNV). In vitro, we show that the surface glycoproteins of ANDV and SNV directly recognize the outermost extracellular repeat domain of PCDH1-a member of the cadherin superfamily7,8-to exploit PCDH1 for entry. In vivo, genetic ablation of PCDH1 renders Syrian golden hamsters highly resistant to a usually lethal ANDV challenge. Targeting PCDH1 could provide strategies to reduce infection and disease caused by New World hantaviruses.}, } @article {pmid30464265, year = {2018}, author = {Parkes, D and Marzeion, B}, title = {Twentieth-century contribution to sea-level rise from uncharted glaciers.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {551-554}, doi = {10.1038/s41586-018-0687-9}, pmid = {30464265}, issn = {1476-4687}, abstract = {Global-mean sea-level rise (GMSLR) during the twentieth century was primarily caused by glacier and ice-sheet mass loss, thermal expansion of ocean water and changes in terrestrial water storage1. Whether based on observations2 or results of climate models3,4, however, the sum of estimates of each of these contributions tends to fall short of the observed GMSLR. Current estimates of the glacier contribution to GMSLR rely on the analysis of glacier inventory data, which are known to undersample the smallest glacier size classes5,6. Here we show that from 1901 to 2015, missing and disappeared glaciers produced a sea-level equivalent (SLE) of approximately 16.7 to 48.0 millimetres. Missing glaciers are those small glaciers that we expect to exist today, owing to regional analyses and theoretical scaling relationships, but that are not represented in the inventories. These glaciers contributed approximately 12.3 to 42.7 millimetres to the historical SLE. Additionally, disappeared glaciers (those that existed in 1901 but had melted away by 2015, and that therefore cannot be included in modern global glacier inventories) made an estimated contribution of between 4.4 and 5.3 millimetres. Failure to consider these uncharted glaciers may be an important cause of difficulties in closing the GMSLR budget during the twentieth century: their contribution is on average between 0.17 and 0.53 millimetres of SLE per year, compared to a budget discrepancy of about 0.5 millimetres of GMSLR per year between 1901 and 1990. Although the uncharted glaciers will have a minimal role in sea-level rise in the future, and are less important after 1990, these findings imply that undiscovered physical processes are not required to close the historical sea-level budget.}, } @article {pmid30464264, year = {2018}, author = {Wiemann, J and Yang, TR and Norell, MA}, title = {Dinosaur egg colour had a single evolutionary origin.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {555-558}, doi = {10.1038/s41586-018-0646-5}, pmid = {30464264}, issn = {1476-4687}, abstract = {Birds are the only living amniotes with coloured eggs1-4, which have long been considered to be an avian innovation1,3. A recent study has demonstrated the presence of both red-brown protoporphyrin IX and blue-green biliverdin5-the pigments responsible for all the variation in avian egg colour-in fossilized eggshell of a nonavian dinosaur6. This raises the fundamental question of whether modern birds inherited egg colour from their nonavian dinosaur ancestors, or whether egg colour evolved independently multiple times. Here we present a phylogenetic assessment of egg colour in nonavian dinosaurs. We applied high-resolution Raman microspectroscopy to eggshells that represent all of the major clades of dinosaurs, and found that egg colour pigments were preserved in all eumaniraptorans: egg colour had a single evolutionary origin in nonavian theropod dinosaurs. The absence of colour in ornithischian and sauropod eggs represents a true signal rather than a taphonomic artefact. Pigment surface maps revealed that nonavian eumaniraptoran eggs were spotted and speckled, and colour pattern diversity in these eggs approaches that in extant birds, which indicates that reproductive behaviours in nonavian dinosaurs were far more complex than previously known3. Depth profiles demonstrated identical mechanisms of pigment deposition in nonavian and avian dinosaur eggs. Birds were not the first amniotes to produce coloured eggs: as with many other characteristics7,8 this is an attribute that evolved deep within the dinosaur tree and long before the spectacular radiation of modern birds.}, } @article {pmid30464263, year = {2018}, author = {Vogler, TO and Wheeler, JR and Nguyen, ED and Hughes, MP and Britson, KA and Lester, E and Rao, B and Betta, ND and Whitney, ON and Ewachiw, TE and Gomes, E and Shorter, J and Lloyd, TE and Eisenberg, DS and Taylor, JP and Johnson, AM and Olwin, BB and Parker, R}, title = {TDP-43 and RNA form amyloid-like myo-granules in regenerating muscle.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {508-513}, doi = {10.1038/s41586-018-0665-2}, pmid = {30464263}, issn = {1476-4687}, support = {F30 AR068881/AR/NIAMS NIH HHS/United States ; R01 AR070360/AR/NIAMS NIH HHS/United States ; R01 GM045443/GM/NIGMS NIH HHS/United States ; R35 GM119575/GM/NIGMS NIH HHS/United States ; T32 GM008497/GM/NIGMS NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; F30 NS093682/NS/NINDS NIH HHS/United States ; R37 GM045443/GM/NIGMS NIH HHS/United States ; R01 AR049446/AR/NIAMS NIH HHS/United States ; }, abstract = {A dominant histopathological feature in neuromuscular diseases, including amyotrophic lateral sclerosis and inclusion body myopathy, is cytoplasmic aggregation of the RNA-binding protein TDP-43. Although rare mutations in TARDBP-the gene that encodes TDP-43-that lead to protein misfolding often cause protein aggregation, most patients do not have any mutations in TARDBP. Therefore, aggregates of wild-type TDP-43 arise in most patients by an unknown mechanism. Here we show that TDP-43 is an essential protein for normal skeletal muscle formation that unexpectedly forms cytoplasmic, amyloid-like oligomeric assemblies, which we call myo-granules, during regeneration of skeletal muscle in mice and humans. Myo-granules bind to mRNAs that encode sarcomeric proteins and are cleared as myofibres mature. Although myo-granules occur during normal skeletal-muscle regeneration, myo-granules can seed TDP-43 amyloid fibrils in vitro and are increased in a mouse model of inclusion body myopathy. Therefore, increased assembly or decreased clearance of functionally normal myo-granules could be the source of cytoplasmic TDP-43 aggregates that commonly occur in neuromuscular disease.}, } @article {pmid30464262, year = {2018}, author = {He, YJ and Meghani, K and Caron, MC and Yang, C and Ronato, DA and Bian, J and Sharma, A and Moore, J and Niraj, J and Detappe, A and Doench, JG and Legube, G and Root, DE and D'Andrea, AD and Drané, P and De, S and Konstantinopoulos, PA and Masson, JY and Chowdhury, D}, title = {DYNLL1 binds to MRE11 to limit DNA end resection in BRCA1-deficient cells.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {522-526}, doi = {10.1038/s41586-018-0670-5}, pmid = {30464262}, issn = {1476-4687}, abstract = {Limited DNA end resection is the key to impaired homologous recombination in BRCA1-mutant cancer cells. Here, using a loss-of-function CRISPR screen, we identify DYNLL1 as an inhibitor of DNA end resection. The loss of DYNLL1 enables DNA end resection and restores homologous recombination in BRCA1-mutant cells, thereby inducing resistance to platinum drugs and inhibitors of poly(ADP-ribose) polymerase. Low BRCA1 expression correlates with increased chromosomal aberrations in primary ovarian carcinomas, and the junction sequences of somatic structural variants indicate diminished homologous recombination. Concurrent decreases in DYNLL1 expression in carcinomas with low BRCA1 expression reduced genomic alterations and increased homology at lesions. In cells, DYNLL1 limits nucleolytic degradation of DNA ends by associating with the DNA end-resection machinery (MRN complex, BLM helicase and DNA2 endonuclease). In vitro, DYNLL1 binds directly to MRE11 to limit its end-resection activity. Therefore, we infer that DYNLL1 is an important anti-resection factor that influences genomic stability and responses to DNA-damaging chemotherapy.}, } @article {pmid30463959, year = {2018}, author = {Pedre, B and Young, D and Charlier, D and Mourenza, Á and Rosado, LA and Marcos-Pascual, L and Wahni, K and Martens, E and G de la Rubia, A and Belousov, VV and Mateos, LM and Messens, J}, title = {Structural snapshots of OxyR reveal the peroxidatic mechanism of H2O2 sensing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11623-E11632}, doi = {10.1073/pnas.1807954115}, pmid = {30463959}, issn = {1091-6490}, abstract = {Hydrogen peroxide (H2O2) is a strong oxidant capable of oxidizing cysteinyl thiolates, yet only a few cysteine-containing proteins have exceptional reactivity toward H2O2 One such example is the prokaryotic transcription factor OxyR, which controls the antioxidant response in bacteria, and which specifically and rapidly reduces H2O2 In this study, we present crystallographic evidence for the H2O2-sensing mechanism and H2O2-dependent structural transition of Corynebacterium glutamicum OxyR by capturing the reduced and H2O2-bound structures of a serine mutant of the peroxidatic cysteine, and the full-length crystal structure of disulfide-bonded oxidized OxyR. In the H2O2-bound structure, we pinpoint the key residues for the peroxidatic reduction of H2O2, and relate this to mutational assays showing that the conserved active-site residues T107 and R278 are critical for effective H2O2 reduction. Furthermore, we propose an allosteric mode of structural change, whereby a localized conformational change arising from H2O2-induced intramolecular disulfide formation drives a structural shift at the dimerization interface of OxyR, leading to overall changes in quaternary structure and an altered DNA-binding topology and affinity at the catalase promoter region. This study provides molecular insights into the overall OxyR transcription mechanism regulated by H2O2.}, } @article {pmid30463958, year = {2018}, author = {Sušac, L and Eddy, MT and Didenko, T and Stevens, RC and Wüthrich, K}, title = {A2A adenosine receptor functional states characterized by 19F-NMR.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12733-12738}, doi = {10.1073/pnas.1813649115}, pmid = {30463958}, issn = {1091-6490}, support = {U54 GM094618/GM/NIGMS NIH HHS/United States ; R01 GM115825/GM/NIGMS NIH HHS/United States ; }, mesh = {Arrestins/metabolism ; Binding Sites ; Cell Membrane/metabolism ; Cytoplasm/metabolism ; Fluorine-19 Magnetic Resonance Imaging/methods ; GTP-Binding Proteins/metabolism ; Humans ; Receptor, Adenosine A2A/*metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction/physiology ; }, abstract = {The human proteome contains 826 G protein-coupled receptors (GPCR), which control a wide array of key physiological functions, making them important drug targets. GPCR functions are based on allosteric coupling from the extracellular orthosteric drug binding site across the cell membrane to intracellular binding sites for partners such as G proteins and arrestins. This signaling process is related to dynamic equilibria in conformational ensembles that can be observed by NMR in solution. A previous high-resolution NMR study of the A2A adenosine receptor (A2AAR) resulted in a qualitative characterization of a network of such local polymorphisms. Here, we used 19F-NMR experiments with probes at the A2AAR intracellular surface, which provides the high sensitivity needed for a refined description of different receptor activation states by ensembles of simultaneously populated conformers and the rates of exchange among them. We observed two agonist-stabilized substates that are not measurably populated in apo-A2AAR and one inactive substate that is not seen in complexes with agonists, suggesting that A2AAR activation includes both induced fit and conformational selection mechanisms. Comparison of A2AAR and a constitutively active mutant established relations between the 19F-NMR spectra and signaling activity, which enabled direct assessment of the difference in basal activity between the native protein and its variant.}, } @article {pmid30463957, year = {2018}, author = {Grabner, CP and Moser, T}, title = {Individual synaptic vesicles mediate stimulated exocytosis from cochlear inner hair cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12811-12816}, doi = {10.1073/pnas.1811814115}, pmid = {30463957}, issn = {1091-6490}, mesh = {Animals ; Auditory Pathways/metabolism/physiology ; Calcium/metabolism ; Cell Membrane/metabolism/physiology ; Cytoskeleton/physiology ; Electric Capacitance ; Excitatory Postsynaptic Potentials/physiology ; Exocytosis/*physiology ; Female ; Hair Cells, Auditory, Inner/metabolism/*physiology ; Hair Cells, Vestibular/metabolism/physiology ; Male ; Membrane Potentials/physiology ; Mice ; Mice, Inbred C57BL ; Synapses/metabolism ; Synaptic Vesicles/metabolism/*physiology ; }, abstract = {Spontaneous excitatory postsynaptic currents (sEPSCs) measured from the first synapse in the mammalian auditory pathway reach a large mean amplitude with a high level of variance (CV between 0.3 and 1). This has led some to propose that each inner hair cell (IHC) ribbon-type active zone (AZ), on average, releases ∼6 synaptic vesicles (SVs) per sEPSC in a coordinated manner. If true, then the predicted change in membrane capacitance (Cm) for such multivesicular fusion events would equate to ∼300 attofarads (aF). Here, we performed cell-attached Cm measurements to directly examine the size of fusion events at the basolateral membrane of IHCs where the AZs are located. The frequency of events depended on the membrane potential and the expression of Cav1.3, the principal Ca2+-channel type of IHCs. Fusion events averaged 40 aF, which equates to a normal-sized SV with an estimated diameter of 37 nm. The calculated SV volumes showed a high degree of variance (CV > 0.6). These results indicate that SVs fused individually with the plasma membrane during spontaneous and evoked release and SV volume may contribute more variability in EPSC amplitude than previously assumed.}, } @article {pmid30463956, year = {2018}, author = {Lim, YW and Chen-Harris, H and Mayba, O and Lianoglou, S and Wuster, A and Bhangale, T and Khan, Z and Mariathasan, S and Daemen, A and Reeder, J and Haverty, PM and Forrest, WF and Brauer, M and Mellman, I and Albert, ML}, title = {Germline genetic polymorphisms influence tumor gene expression and immune cell infiltration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11701-E11710}, doi = {10.1073/pnas.1804506115}, pmid = {30463956}, issn = {1091-6490}, abstract = {Cancer immunotherapy has emerged as an effective therapy in a variety of cancers. However, a key challenge in the field is that only a subset of patients who receive immunotherapy exhibit durable response. It has been hypothesized that host genetics influences the inherent immune profiles of patients and may underlie their differential response to immunotherapy. Herein, we systematically determined the association of common germline genetic variants with gene expression and immune cell infiltration of the tumor. We identified 64,094 expression quantitative trait loci (eQTLs) that associated with 18,210 genes (eGenes) across 24 human cancers. Overall, eGenes were enriched for their being involved in immune processes, suggesting that expression of immune genes can be shaped by hereditary genetic variants. We identified the endoplasmic reticulum aminopeptidase 2 (ERAP2) gene as a pan-cancer type eGene whose expression levels stratified overall survival in a subset of patients with bladder cancer receiving anti-PD-L1 (atezolizumab) therapy. Finally, we identified 103 gene signature QTLs (gsQTLs) that were associated with predicted immune cell abundance within the tumor microenvironment. Our findings highlight the impact of germline SNPs on cancer-immune phenotypes and response to therapy; and these analyses provide a resource for integration of germline genetics as a component of personalized cancer immunotherapy.}, } @article {pmid30463955, year = {2018}, author = {Emrick, JJ and Mathur, A and Wei, J and Gracheva, EO and Gronert, K and Rosenblum, MD and Julius, D}, title = {Tissue-specific contributions of Tmem79 to atopic dermatitis and mast cell-mediated histaminergic itch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E12091-E12100}, doi = {10.1073/pnas.1814132115}, pmid = {30463955}, issn = {1091-6490}, support = {F30 DE023476/DE/NIDCR NIH HHS/United States ; R35 NS105038/NS/NINDS NIH HHS/United States ; R01 EY026082/EY/NEI NIH HHS/United States ; R01 NS081115/NS/NINDS NIH HHS/United States ; K08 AR070910/AR/NIAMS NIH HHS/United States ; }, abstract = {Atopic dermatitis (AD) is the most common skin disease in children. It is characterized by relapsing inflammation, skin-barrier defects, and intractable itch. However, the pathophysiology of itch in AD remains enigmatic. Here, we examine the contribution of Tmem79, an orphan transmembrane protein linked to AD in both mice and humans. We show that Tmem79 is expressed by both keratinocytes and sensory neurons, but that loss of keratinocytic Tmem79 is sufficient to elicit robust scratching. Tmem79-/- mice demonstrate an accumulation of dermal mast cells, which are diminished following chronic treatment with cyclooxygenase inhibitors and an EP3 receptor antagonist. In Tmem79-/- mice, mast cell degranulation produces histaminergic itch in a histamine receptor 1/histamine receptor 4 (H4R/H1R)-dependent manner that may involve activation of TRPV1- afferents. TMEM79 has limited sequence homology to a family of microsomal glutathione transferases and confers protection from cellular accumulation of damaging reactive species, and may thus play a role in regulating oxidative stress. In any case, mechanistic insights from this model suggest that therapeutics targeting PGE2 and/or H1R/H4R histaminergic signaling pathways may represent useful avenues to treat Tmem79-associated AD itch. Our findings suggest that individuals with mutations in Tmem79 develop AD due to the loss of protection from oxidative stress.}, } @article {pmid30463954, year = {2018}, author = {Ren, J and Wang, S and Chen, H and Wang, W and Huo, L and Feng, W}, title = {Coiled-coil 1-mediated fastening of the neck and motor domains for kinesin-3 autoinhibition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11933-E11942}, doi = {10.1073/pnas.1811209115}, pmid = {30463954}, issn = {1091-6490}, abstract = {In kinesin-3, the coiled-coil 1 (CC1) can sequester the preceding neck coil (NC) for autoinhibition, but the underlying mechanism is poorly understood. Here, we determined the structures of the uninhibited motor domain (MD)-NC dimer and inhibited MD-NC-CC1 monomer of kinesin-3 KIF13B. In the MD-NC-CC1 monomer, CC1 is broken into two short helices that unexpectedly interact with both the NC and the MD. Compared with the MD-NC dimer, the CC1-mediated integration of NC and MD not only blocks the NC dimer formation, but also prevents the neck linker (NL) undocking and the ADP release from the MD. Mutations of the essential residues in the interdomain interaction interface in the MD-NC-CC1 monomer restored the MD activity. Thus, CC1 fastens the neck domain and MD and inhibits both NC and NL. This CC1-mediated lockdown of the entire neck domain may represent a paradigm for kinesin autoinhibition that could be applicable to other kinesin-3 motors.}, } @article {pmid30463953, year = {2018}, author = {Galburt, EA}, title = {The calculation of transcript flux ratios reveals single regulatory mechanisms capable of activation and repression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11604-E11613}, doi = {10.1073/pnas.1809454115}, pmid = {30463953}, issn = {1091-6490}, support = {R01 GM107544/GM/NIGMS NIH HHS/United States ; }, abstract = {The regulation of transcription allows cells to adjust the rate of RNA polymerases (RNAPs) initiated in a promoter-specific manner. Classically, transcription factors are directed to a subset of promoters via the recognition of DNA sequence motifs. However, a unique class of regulators is recruited directly through interactions with RNAP. Surprisingly, these factors may still possess promoter specificity, and it has been postulated that the same kinetic mechanism leads to different regulatory outcomes depending on a promoter's basal rate constants. However, mechanistic studies of regulation typically report factor activity in terms of changes in the thermodynamics or kinetics of individual steps or states while qualitatively linking these observations to measured changes in transcript production. Here, I present online calculators that allow for the direct testing of mechanistic hypotheses by calculating the steady-state transcript flux in the presence and absence of a factor as a function of initiation rate constants. By evaluating how the flux ratio of a single kinetic mechanism varies across promoter space, quantitative insights into the potential of a mechanism to generate promoter-specific regulatory outcomes are obtained. Using these calculations, I predict that the mycobacterial transcription factor CarD is capable of repression in addition to its known role as an activator of ribosomal genes. In addition, a modification of the mechanism of the stringent response factors DksA/guanosine 5'-diphosphate 3'-diphosphate (ppGpp) is proposed based on their ability to differentially regulate transcription across promoter space. Overall, I conclude that a multifaceted kinetic mechanism is a requirement for differential regulation by this class of factors.}, } @article {pmid30463952, year = {2018}, author = {Ceballos, BM and Yang, JY}, title = {Directing the reactivity of metal hydrides for selective CO2 reduction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12686-12691}, doi = {10.1073/pnas.1811396115}, pmid = {30463952}, issn = {1091-6490}, abstract = {A critical challenge in electrocatalytic CO2 reduction to renewable fuels is product selectivity. Desirable products of CO2 reduction require proton equivalents, but key catalytic intermediates can also be competent for direct proton reduction to H2 Understanding how to manage divergent reaction pathways at these shared intermediates is essential to achieving high selectivity. Both proton reduction to hydrogen and CO2 reduction to formate generally proceed through a metal hydride intermediate. We apply thermodynamic relationships that describe the reactivity of metal hydrides with H+ and CO2 to generate a thermodynamic product diagram, which outlines the free energy of product formation as a function of proton activity and hydricity (∆GH-), or hydride donor strength. The diagram outlines a region of metal hydricity and proton activity in which CO2 reduction is favorable and H+ reduction is suppressed. We apply our diagram to inform our selection of [Pt(dmpe)2](PF6)2 as a potential catalyst, because the corresponding hydride [HPt(dmpe)2]+ has the correct hydricity to access the region where selective CO2 reduction is possible. We validate our choice experimentally; [Pt(dmpe)2](PF6)2 is a highly selective electrocatalyst for CO2 reduction to formate (>90% Faradaic efficiency) at an overpotential of less than 100 mV in acetonitrile with no evidence of catalyst degradation after electrolysis. Our report of a selective catalyst for CO2 reduction illustrates how our thermodynamic diagrams can guide selective and efficient catalyst discovery.}, } @article {pmid30463951, year = {2018}, author = {Bertho, S and Herpin, A and Branthonne, A and Jouanno, E and Yano, A and Nicol, B and Muller, T and Pannetier, M and Pailhoux, E and Miwa, M and Yoshizaki, G and Schartl, M and Guiguen, Y}, title = {The unusual rainbow trout sex determination gene hijacked the canonical vertebrate gonadal differentiation pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12781-12786}, doi = {10.1073/pnas.1803826115}, pmid = {30463951}, issn = {1091-6490}, mesh = {Animals ; Aromatase/genetics ; Cell Differentiation/genetics ; Cell Nucleus/genetics ; Estrogens/genetics ; Female ; Forkhead Box Protein L2/genetics ; Gene Regulatory Networks/*genetics ; Gonads/*physiology ; Male ; Oncorhynchus mykiss/*genetics ; Promoter Regions, Genetic/genetics ; Sex Determination Processes/*genetics ; Sex Differentiation/*genetics ; Testis/metabolism ; Translocation, Genetic/genetics ; }, abstract = {Evolutionary novelties require rewiring of transcriptional networks and/or the evolution of new gene functions. Sex determination (SD), one of the most plastic evolutionary processes, requires such novelties. Studies on the evolution of vertebrate SD revealed that new master SD genes are generally recruited from genes involved in the downstream SD regulatory genetic network. Only a single exception to this rule is currently known in vertebrates: the intriguing case of the salmonid master SD gene (sdY), which arose from duplication of an immune-related gene. This exception immediately posed the question of how a gene outside from the classical sex differentiation cascade could acquire its function as a male SD gene. Here we show that SdY became integrated in the classical vertebrate sex differentiation cascade by interacting with the Forkhead box domain of the female-determining transcription factor, Foxl2. In the presence of Foxl2, SdY is translocated to the nucleus where the SdY:Foxl2 complex prevents activation of the aromatase (cyp19a1a) promoter in cooperation with Nr5a1 (Sf1). Hence, by blocking a positive loop of regulation needed for the synthesis of estrogens in the early differentiating gonad, SdY disrupts a preset female differentiation pathway, consequently allowing testicular differentiation to proceed. These results also suggest that the evolution of unusual vertebrate master sex determination genes recruited from outside the classical pathway like sdY is strongly constrained by their ability to interact with the canonical gonadal differentiation pathway.}, } @article {pmid30463950, year = {2018}, author = {Trivedi, U and Madsen, JS and Everett, J and Fell, C and Russel, J and Haaber, J and Crosby, HA and Horswill, AR and Burmølle, M and Rumbaugh, KP and Sørensen, SJ}, title = {Staphylococcus aureus coagulases are exploitable yet stable public goods in clinically relevant conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11771-E11779}, doi = {10.1073/pnas.1804850115}, pmid = {30463950}, issn = {1091-6490}, abstract = {Coagulation is an innate defense mechanism intended to limit blood loss and trap invading pathogens during infection. However, Staphylococcus aureus has the ability to hijack the coagulation cascade and generate clots via secretion of coagulases. Although many S. aureus have this characteristic, some do not. The population dynamics regarding this defining trait have yet to be explored. We report here that coagulases are public goods that confer protection against antimicrobials and immune factors within a local population or community, thus promoting growth and virulence. By utilizing variants of a methicillin-resistant S. aureus we infer that the secretion of coagulases is a cooperative trait, which is subject to exploitation by invading mutants that do not produce the public goods themselves. However, overexploitation, "tragedy of the commons," does not occur at clinically relevant conditions. Our micrographs indicate this is due to spatial segregation and population viscosity. These findings emphasize the critical role of coagulases in a social evolution context and provide a possible explanation as to why the secretion of these public goods is maintained in mixed S. aureus communities.}, } @article {pmid30463949, year = {2018}, author = {Mao, M and Yang, X and Bennett, GM}, title = {Evolution of host support for two ancient bacterial symbionts with differentially degraded genomes in a leafhopper host.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11691-E11700}, doi = {10.1073/pnas.1811932115}, pmid = {30463949}, issn = {1091-6490}, abstract = {Plant sap-feeding insects (Hemiptera) rely on bacterial symbionts for nutrition absent in their diets. These bacteria experience extreme genome reduction and require genetic resources from their hosts, particularly for basic cellular processes other than nutrition synthesis. The host-derived mechanisms that complete these processes have remained poorly understood. It is also unclear how hosts meet the distinct needs of multiple bacterial partners with differentially degraded genomes. To address these questions, we investigated the cell-specific gene-expression patterns in the symbiotic organs of the aster leafhopper (ALF), Macrosteles quadrilineatus (Cicadellidae). ALF harbors two intracellular symbionts that have two of the smallest known bacterial genomes: Nasuia (112 kb) and Sulcia (190 kb). Symbionts are segregated into distinct host cell types (bacteriocytes) and vary widely in their basic cellular capabilities. ALF differentially expresses thousands of genes between the bacteriocyte types to meet the functional needs of each symbiont, including the provisioning of metabolites and support of cellular processes. For example, the host highly expresses genes in the bacteriocytes that likely complement gene losses in nucleic acid synthesis, DNA repair mechanisms, transcription, and translation. Such genes are required to function in the bacterial cytosol. Many host genes comprising these support mechanisms are derived from the evolution of novel functional traits via horizontally transferred genes, reassigned mitochondrial support genes, and gene duplications with bacteriocyte-specific expression. Comparison across other hemipteran lineages reveals that hosts generally support the incomplete symbiont cellular processes, but the origins of these support mechanisms are generally specific to the host-symbiont system.}, } @article {pmid30463948, year = {2018}, author = {Geron, M and Kumar, R and Zhou, W and Faraldo-Gómez, JD and Vásquez, V and Priel, A}, title = {TRPV1 pore turret dictates distinct DkTx and capsaicin gating.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11837-E11846}, doi = {10.1073/pnas.1809662115}, pmid = {30463948}, issn = {1091-6490}, abstract = {Many neurotoxins inflict pain by targeting receptors expressed on nociceptors, such as the polymodal cationic channel TRPV1. The tarantula double-knot toxin (DkTx) is a peptide with an atypical bivalent structure, providing it with the unique capability to lock TRPV1 in its open state and evoke an irreversible channel activation. Here, we describe a distinct gating mechanism of DkTx-evoked TRPV1 activation. Interestingly, DkTx evokes significantly smaller TRPV1 macroscopic currents than capsaicin, with a significantly lower unitary conductance. Accordingly, while capsaicin evokes aversive behaviors in TRPV1-transgenic Caenorhabditis elegans, DkTx fails to evoke such response at physiological concentrations. To determine the structural feature(s) responsible for this phenomenon, we engineered and evaluated a series of mutated toxins and TRPV1 channels. We found that elongating the DkTx linker, which connects its two knots, increases channel conductance compared with currents elicited by the native toxin. Importantly, deletion of the TRPV1 pore turret, a stretch of amino acids protruding out of the channel's outer pore region, is sufficient to produce both full conductance and aversive behaviors in response to DkTx. Interestingly, this deletion decreases the capsaicin-evoked channel activation. Taken together with structure modeling analysis, our results demonstrate that the TRPV1 pore turret restricts DkTx-mediated pore opening, probably through steric hindrance, limiting the current size and mitigating the evoked downstream physiological response. Overall, our findings reveal that DkTx and capsaicin elicit distinct TRPV1 gating mechanisms and subsequent pain responses. Our results also indicate that the TRPV1 pore turret regulates the mechanisms of channel gating and permeation.}, } @article {pmid30463947, year = {2018}, author = {Smith, MA}, title = {Janzen's mountain passes hypothesis is comprehensively tested in its fifth decade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12337-12339}, doi = {10.1073/pnas.1817774115}, pmid = {30463947}, issn = {1091-6490}, } @article {pmid30463946, year = {2018}, author = {Park, SJ and Kim, JM and Kim, J and Hur, J and Park, S and Kim, K and Shin, HJ and Chwae, YJ}, title = {Molecular mechanisms of biogenesis of apoptotic exosome-like vesicles and their roles as damage-associated molecular patterns.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11721-E11730}, doi = {10.1073/pnas.1811432115}, pmid = {30463946}, issn = {1091-6490}, abstract = {Recent research has led to contradictory notions regarding the conventional theory that apoptotic cell death can evoke inflammatory or immunogenic responses orchestrated by released damage-associated patterns (DAMPs). By inducing IL-1β from bone marrow-derived macrophages in an effort to determine the inflammatory mediators released from apoptotic cells, we found that exosomal fractions called "apoptotic exosome-like vesicles" (AEVs) prepared from apoptotic-conditioned medium were the main inflammatory factors. These AEVs showed characteristics of exosomes in their size, density, morphology, and protein expression but had unique marker proteins, sphingosine-1-phosphate receptors 1 and 3 (S1PR1 and 3). Their biogenesis was completely dependent on cellular sphingosine-1-phosphate (S1P)/S1PRs signaling from multiple fine spindles of plasma membrane accompanied by F-actin, S1PR1, S1PR3, and CD63 at the early apoptotic phase and progressing to the maturation of F-actin-guided multivesicular endosomes mediated by Gβγ subunits of S1PRs downstream. S1P-loaded S1PRs on AEVs were critical factors for inducing IL-1β via NF-κB transcriptional factor and p38 MAPK, possibly through the RHOA/NOD2 axis, in differentiating macrophages. The AEVs induced genes of proinflammatory cytokines, chemokines, and mediators in both in vitro and in vivo models. In conclusion, AEVs could be key inflammatory mediators, acting as DAMPs that could explain the pathogeneses of various chronic inflammations, autoimmune diseases, or cancers in the future.}, } @article {pmid30463945, year = {2018}, author = {Liu, QH and Ajelli, M and Aleta, A and Merler, S and Moreno, Y and Vespignani, A}, title = {Measurability of the epidemic reproduction number in data-driven contact networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12680-12685}, doi = {10.1073/pnas.1811115115}, pmid = {30463945}, issn = {1091-6490}, support = {U54 GM111274/GM/NIGMS NIH HHS/United States ; }, abstract = {The basic reproduction number is one of the conceptual cornerstones of mathematical epidemiology. Its classical definition as the number of secondary cases generated by a typical infected individual in a fully susceptible population finds a clear analytical expression in homogeneous and stratified mixing models. Along with the generation time (the interval between primary and secondary cases), the reproduction number allows for the characterization of the dynamics of an epidemic. A clear-cut theoretical picture, however, is hardly found in real data. Here, we infer from highly detailed sociodemographic data two multiplex contact networks representative of a subset of the Italian and Dutch populations. We then simulate an infection transmission process on these networks accounting for the natural history of influenza and calibrated on empirical epidemiological data. We explicitly measure the reproduction number and generation time, recording all individual-level transmission events. We find that the classical concept of the basic reproduction number is untenable in realistic populations, and it does not provide any conceptual understanding of the epidemic evolution. This departure from the classical theoretical picture is not due to behavioral changes and other exogenous epidemiological determinants. Rather, it can be simply explained by the (clustered) contact structure of the population. Finally, we provide evidence that methodologies aimed at estimating the instantaneous reproduction number can operationally be used to characterize the correct epidemic dynamics from incidence data.}, } @article {pmid30463944, year = {2018}, author = {Miller, NT and Burnap, RL}, title = {Navigating the fitness landscape using multiallele genome editing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12547-12549}, doi = {10.1073/pnas.1818285115}, pmid = {30463944}, issn = {1091-6490}, mesh = {Biological Phenomena ; *Cyanobacteria ; *Gene Editing ; Genomics ; }, } @article {pmid30463943, year = {2018}, author = {Ospadov, E and Tao, J and Staroverov, VN and Perdew, JP}, title = {Visualizing atomic sizes and molecular shapes with the classical turning surface of the Kohn-Sham potential.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11578-E11585}, doi = {10.1073/pnas.1814300115}, pmid = {30463943}, issn = {1091-6490}, abstract = {The Kohn-Sham potential [Formula: see text] is the effective multiplicative operator in a noninteracting Schrödinger equation that reproduces the ground-state density of a real (interacting) system. The sizes and shapes of atoms, molecules, and solids can be defined in terms of Kohn-Sham potentials in a nonarbitrary way that accords with chemical intuition and can be implemented efficiently, permitting a natural pictorial representation for chemistry and condensed-matter physics. Let [Formula: see text] be the maximum occupied orbital energy of the noninteracting electrons. Then the equation [Formula: see text] defines the surface at which classical electrons with energy [Formula: see text] would be turned back and thus determines the surface of any electronic object. Atomic and ionic radii defined in this manner agree well with empirical estimates, show regular chemical trends, and allow one to identify the type of chemical bonding between two given atoms by comparing the actual internuclear distance to the sum of atomic radii. The molecular surfaces can be fused (for a covalent bond), seamed (ionic bond), necked (hydrogen bond), or divided (van der Waals bond). This contribution extends the pioneering work of Z.-Z. Yang et al. [Yang ZZ, Davidson ER (1997) Int J Quantum Chem 62:47-53; Zhao DX, et al. (2018) Mol Phys 116:969-977] by our consideration of the Kohn-Sham potential, protomolecules, doubly negative atomic ions, a bond-type parameter, seamed and necked molecular surfaces, and a more extensive table of atomic and ionic radii that are fully consistent with expected periodic trends.}, } @article {pmid30463942, year = {2018}, author = {Vogt, T and Horn, S and Grannan, AM and Aurnou, JM}, title = {Jump rope vortex in liquid metal convection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12674-12679}, doi = {10.1073/pnas.1812260115}, pmid = {30463942}, issn = {1091-6490}, abstract = {Understanding large-scale circulations (LSCs) in turbulent convective systems is important for the study of stars, planets, and in many industrial applications. The canonical model of the LSC is quasi-planar with additional horizontal sloshing and torsional modes [Brown E, Ahlers G (2009) J Fluid Mech 638:383-400; Funfschilling D, Ahlers G (2004) Phys Rev Lett 92:194502; Xi HD et al. (2009) Phys Rev Lett 102:044503; Zhou Q et al. (2009) J Fluid Mech 630:367-390]. Using liquid gallium as the working fluid, we show, via coupled laboratory-numerical experiments in tanks with aspect ratios greater than unity ([Formula: see text]), that the LSC takes instead the form of a "jump rope vortex," a strongly 3D mode that periodically orbits around the tank following a motion much like a jump rope on a playground. Further experiments show that this jump rope flow also exists in more viscous fluids such as water, albeit with a far smaller signal. Thus, this jump rope mode is an essential component of the turbulent convection that underlies our observations of natural systems.}, } @article {pmid30463619, year = {2018}, author = {Liao, L and Li, K and Li, K and Yang, C and Tian, Q}, title = {A multiple kernel density clustering algorithm for incomplete datasets in bioinformatics.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {111}, pmid = {30463619}, issn = {1752-0509}, abstract = {BACKGROUND: While there are a large number of bioinformatics datasets for clustering, many of them are incomplete, i.e., missing attribute values in some data samples needed by clustering algorithms. A variety of clustering algorithms have been proposed in the past years, but they usually are limited to cluster on the complete dataset. Besides, conventional clustering algorithms cannot obtain a trade-off between accuracy and efficiency of the clustering process since many essential parameters are determined by the human user's experience.

RESULTS: The paper proposes a Multiple Kernel Density Clustering algorithm for Incomplete datasets called MKDCI. The MKDCI algorithm consists of recovering missing attribute values of input data samples, learning an optimally combined kernel for clustering the input dataset, reducing dimensionality with the optimal kernel based on multiple basis kernels, detecting cluster centroids with the Isolation Forests method, assigning clusters with arbitrary shape and visualizing the results.

CONCLUSIONS: Extensive experiments on several well-known clustering datasets in bioinformatics field demonstrate the effectiveness of the proposed MKDCI algorithm. Compared with existing density clustering algorithms and parameter-free clustering algorithms, the proposed MKDCI algorithm tends to automatically produce clusters of better quality on the incomplete dataset in bioinformatics.}, } @article {pmid30463617, year = {2018}, author = {Sun, S and Klebaner, F and Zhang, X and Tian, T}, title = {Instantaneous mutation rate in cancer initiation and progression.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {110}, pmid = {30463617}, issn = {1752-0509}, abstract = {BACKGROUND: Cancer is one of the leading causes for the morbidity and mortality worldwide. Although substantial studies have been conducted theoretically and experimentally in recent years, it is still a challenge to explore the mechanisms of cancer initiation and progression. The investigation for these problems is very important for the diagnosis of cancer diseases and development of treatment schemes.

RESULTS: To accurately describe the process of cancer initiation, we propose a new concept of gene initial mutation rate based on our recently designed mathematical model using the non-constant mutation rate. Unlike the widely-used average gene mutation rate that depends on the number of mutations, the gene initial mutation rate can be used to describe the initiation process of a single patient. In addition, we propose the instantaneous tumour doubling time that is a continuous function of time based on the non-constant mutation rate. Our proposed concepts are supported by the clinic data of seven patients with advanced pancreatic cancer. The regression results suggest that, compared with the average mutation rate, the estimated initial mutation rate has a larger value of correlation coefficient with the patient survival time. We also provide the estimated tumour size of these seven patients over time.

CONCLUSIONS: The proposed concepts can be used to describe the cancer initiation and progression for different patients more accurately. Since a quantitative understanding of cancer progression is important for clinical treatment, our proposed model and calculated results may provide insights into the development of treatment schemes and also have other clinic implications.}, } @article {pmid30463605, year = {2018}, author = {Santonja-Medina, F and García-Sanz, MP and Santonja-Renedo, S and García-Estañ, J}, title = {Mismatch between student and tutor evaluation of training needs: a study of traumatology rotations.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {826}, pmid = {30463605}, issn = {1756-0500}, abstract = {OBJECTIVE: An e-portfolio was used to determine the optimal number of times students need to repeat a procedure before they are fully capable of performing it without supervision. The results were compared with the actual number of repetitions performed during the internship period. We also asked these students and their teachers about the optimal number of times each skill should be repeated before it could be considered fully acquired. The questionnaire was answered by 98.6% of the students and 70.3% of their teachers.

RESULTS: Both students and teachers agreed on a similar optimal value for 16 out of the 21 clinical procedures selected; in the remaining 5, teachers thought that students needed to repeat the procedure more times than the number stated by students. When these optimal values were compared with the actual values recorded in the portfolio during the internships, it was found that about half of all clinical procedures were carried out fewer times than expected, thus providing important feedback about the rotation-based training process. Quantitative information collected in the portfolios revealed a moderate mismatch between students' and teachers' perceptions of training needs.}, } @article {pmid30463602, year = {2018}, author = {Castilho, VVS and Gonçalves, KCS and Rebello, KM and Baptista, LPR and Sangenito, LS and Santos, HLC and Branquinha, MH and Santos, ALS and Menna-Barreto, RFS and Guimarães, AC and d'Avila-Levy, CM}, title = {Docking simulation between HIV peptidase inhibitors and Trypanosoma cruzi aspartyl peptidase.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {825}, pmid = {30463602}, issn = {1756-0500}, support = {001//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BR)/ ; x//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro (BR)/ ; x//Fundação Oswaldo Cruz (BR)/ ; x//Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)/ ; }, abstract = {OBJECTIVE: The low investment in research, diagnosis and treatment are factors that contribute to the continuity of Chagas' disease as a neglected tropical diseases (NTDs). In this context, the repositioning of drugs represents a useful strategy, in the search for new chemotherapeutic approaches for NTDs. HIV aspartic peptidase inhibitors (HIV IPs) are good candidates for drug repurposing. Here, we modeled the three dimensional structure of an aspartyl peptidase of Trypanosoma cruzi, the causative agent of Chagas' disease, aligned it to the HIV aspartyl peptidase and performed docking binding assays with the HIV PIs.

RESULTS: The 3D structure confirmed the presence of acid aspartic residues, which are critical to enzyme activity. The docking experiment revealed that HIV IPs bind to the active site of the enzyme, being ritonavir and lopinavir the ones with greater affinity. Benznidazole presented the worst binding affinity, this drug is currently used in Chagas' disease treatment and was included as negative control. These results together with previous data on the trypanocidal effect of the HIV PIs support the hypothesis that a T. cruzi aspartyl peptidase can be the intracellular target of these inhibitors. However, the direct demonstration of the inhibition of T. cruzi aspartyl peptidase activity by HIV PIs is still a goal to be persuaded.}, } @article {pmid30463571, year = {2018}, author = {Menon, V and Yarahmadian, S and Rezania, V}, title = {Novel EM based ML Kalman estimation framework for superresolution of stochastic three-states microtubule signal.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {112}, pmid = {30463571}, issn = {1752-0509}, abstract = {BACKGROUND: Recent research has found that abnormal functioning of Microtubules (MTs) could be linked to fatal diseases such as Alzheimer's. Hence, there is an imminent need to understand the implications of MTs for disease- diagnosis. However, studies of cellular processes like MTs are often constrained by physical limitations of their data acquisition systems such as optical microscopes and are vulnerable to either destruction of the specimen or the probe. In addition, study of MTs is challenged with non-uniform sampling of the MT dynamic instability phenomenon relative to its time-lapse observation of the cellular processes. Thus, the above caveats limit the overall period of time that the MT data can be collected, thereby causing limited data availability scenario.

RESULTS: In this work, two novel superresolution frameworks based on Expectation Maximization (EM) based Maximum Likelihood (ML) estimation using Kalman filters (MLK) technique are proposed to address the issues of non-uniform sampling and limited data availability of MT signals. The proposed MLK methods optimizes prediction of missing observations in the MT signal through information extraction using correlation-based patch processing and principal component analysis -based mutual information. Experimental results prove that the proposed MLK-based superresolution methods outperformed nonlinear interpolation and compressed sensing methods.

CONCLUSIONS: This work aims to address limited data availability and data/observation loss incurred due to non-uniform sampling of biological signals such as MTs. For this purpose, statistical modelling of stochastic MT signals using EM based ML driven Kalman estimation (MLK) is considered as a fundamental framework for prediction of missing MT observations. It was experimentally validated that the proposed superresolution methods provided superior overall performance, better MT signal estimation using fewer samples, high SNR, low errors, and better MT parameter estimation than other methods.}, } @article {pmid30463558, year = {2018}, author = {Jeong, JE and Qiu, P}, title = {Quantifying the relative importance of experimental data points in parameter estimation.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {103}, pmid = {30463558}, issn = {1752-0509}, abstract = {BACKGROUND: Ordinary differential equations (ODEs) are often used to understand biological processes. Since ODE-based models usually contain many unknown parameters, parameter estimation is an important step toward deeper understanding of the process. Parameter estimation is often formulated as a least squares optimization problem, where all experimental data points are considered as equally important. However, this equal-weight formulation ignores the possibility of existence of relative importance among different data points, and may lead to misleading parameter estimation results. Therefore, we propose to introduce weights to account for the relative importance of different data points when formulating the least squares optimization problem. Each weight is defined by the uncertainty of one data point given the other data points. If one data point can be accurately inferred given the other data, the uncertainty of this data point is low and the importance of this data point is low. Whereas, if inferring one data point from the other data is almost impossible, it contains a huge uncertainty and carries more information for estimating parameters.

RESULTS: G1/S transition model with 6 parameters and 12 parameters, and MAPK module with 14 parameters were used to test the weighted formulation. In each case, evenly spaced experimental data points were used. Weights calculated in these models showed similar patterns: high weights for data points in dynamic regions and low weights for data points in flat regions. We developed a sampling algorithm to evaluate the weighted formulation, and demonstrated that the weighted formulation reduced the redundancy in the data. For G1/S transition model with 12 parameters, we examined unevenly spaced experimental data points, strategically sampled to have more measurement points where the weights were relatively high, and fewer measurement points where the weights were relatively low. This analysis showed that the proposed weights can be used for designing measurement time points.

CONCLUSIONS: Giving a different weight to each data point according to its relative importance compared to other data points is an effective method for improving robustness of parameter estimation by reducing the redundancy in the experimental data.}, } @article {pmid30463556, year = {2018}, author = {Lu, J and Sun, J and Wang, X and Kranzler, H and Gelernter, J and Bi, J}, title = {Inferring phenotypes from substance use via collaborative matrix completion.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {104}, pmid = {30463556}, issn = {1752-0509}, support = {K02 DA043063/DA/NIDA NIH HHS/United States ; R01 DA037349/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: Although substance use disorders (SUDs) are heritable, few genetic risk factors for them have been identified, in part due to the small sample sizes of study populations. To address this limitation, researchers have aggregated subjects from multiple existing genetic studies, but these subjects can have missing phenotypic information, including diagnostic criteria for certain substances that were not originally a focus of study. Recent advances in addiction neurobiology have shown that comorbid SUDs (e.g., the abuse of multiple substances) have similar genetic determinants, which makes it possible to infer missing SUD diagnostic criteria using criteria from another SUD and patient genotypes through statistical modeling.

RESULTS: We propose a new approach based on matrix completion techniques to integrate features of comorbid health conditions and individual's genotypes to infer unreported diagnostic criteria for a disorder. This approach optimizes a bi-linear model that uses the interactions between known disease correlations and candidate genes to impute missing criteria. An efficient stochastic and parallel algorithm was developed to optimize the model with a speed 20 times greater than the classic sequential algorithm. It was tested on 3441 subjects who had both cocaine and opioid use disorders and successfully inferred missing diagnostic criteria with consistently better accuracy than other recent statistical methods.

CONCLUSIONS: The proposed matrix completion imputation method is a promising tool to impute unreported or unobserved symptoms or criteria for disease diagnosis. Integrating data at multiple scales or from heterogeneous sources may help improve the accuracy of phenotype imputation.}, } @article {pmid30463553, year = {2018}, author = {He, F and Wang, R and Li, J and Bao, L and Xu, D and Zhao, X}, title = {Large-scale prediction of protein ubiquitination sites using a multimodal deep architecture.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {109}, pmid = {30463553}, issn = {1752-0509}, abstract = {BACKGROUND: Ubiquitination, which is also called "lysine ubiquitination", occurs when an ubiquitin is attached to lysine (K) residues in targeting proteins. As one of the most important post translational modifications (PTMs), it plays the significant role not only in protein degradation, but also in other cellular functions. Thus, systematic anatomy of the ubiquitination proteome is an appealing and challenging research topic. The existing methods for identifying protein ubiquitination sites can be divided into two kinds: mass spectrometry and computational methods. Mass spectrometry-based experimental methods can discover ubiquitination sites from eukaryotes, but are time-consuming and expensive. Therefore, it is priority to develop computational approaches that can effectively and accurately identify protein ubiquitination sites.

RESULTS: The existing computational methods usually require feature engineering, which may lead to redundancy and biased representations. While deep learning is able to excavate underlying characteristics from large-scale training data via multiple-layer networks and non-linear mapping operations. In this paper, we proposed a deep architecture within multiple modalities to identify the ubiquitination sites. First, according to prior knowledge and biological knowledge, we encoded protein sequence fragments around candidate ubiquitination sites into three modalities, namely raw protein sequence fragments, physico-chemical properties and sequence profiles, and designed different deep network layers to extract the hidden representations from them. Then, the generative deep representations corresponding to three modalities were merged to build the final model. We performed our algorithm on the available largest scale protein ubiquitination sites database PLMD, and achieved 66.4% specificity, 66.7% sensitivity, 66.43% accuracy, and 0.221 MCC value. A number of comparative experiments also indicated that our multimodal deep architecture outperformed several popular protein ubiquitination site prediction tools.

CONCLUSION: The results of comparative experiments validated the effectiveness of our deep network and also displayed that our method outperformed several popular protein ubiquitination site prediction tools. The source codes of our proposed method are available at https://github.com/jiagenlee/deepUbiquitylation .}, } @article {pmid30463550, year = {2018}, author = {Bardini, R and Di Carlo, S and Politano, G and Benso, A}, title = {Modeling antibiotic resistance in the microbiota using multi-level Petri Nets.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {108}, pmid = {30463550}, issn = {1752-0509}, abstract = {BACKGROUND: The unregulated use of antibiotics not only in clinical practice but also in farm animals breeding is causing a unprecedented growth of antibiotic resistant bacterial strains. This problem can be analyzed at different levels, from the antibiotic resistance spreading dynamics at the host population level down to the molecular mechanisms at the bacteria level. In fact, antibiotic administration policies and practices affect the societal system where individuals developing resistance interact with each other and with the environment. Each individual can be seen as a meta-organism together with its associated microbiota, which proves to have a prominent role in the resistance spreading dynamics. Eventually, in each microbiota, bacterial population dynamics and vertical or horizontal gene transfer events activate cellular and molecular mechanisms for resistance spreading that can also be possible targets for its prevention.

RESULTS: In this work we show how to use the Nets-Within-Nets formalism to model the dynamics between different antibiotic administration protocols and antibiotic resistance, both at the individuals population and at the single microbiota level. Three application examples are presented to show the flexibility of this approach in integrating heterogeneous information in the same model, a fundamental property when creating computational models complex biological systems. Simulations allow to explicitly take into account timing and stochastic events.

CONCLUSIONS: This work demonstrates how the NWN formalism can be used to efficiently model antibiotic resistance population dynamics at different levels of detail. The proposed modeling approach not only provides a valuable tool for investigating causal, quantitative relations between different events and mechanisms, but can be also used as a valid support for decision making processes and protocol development.}, } @article {pmid30463546, year = {2018}, author = {Yuan, Y and Xun, G and Jia, K and Zhang, A}, title = {A multi-context learning approach for EEG epileptic seizure detection.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {107}, pmid = {30463546}, issn = {1752-0509}, abstract = {BACKGROUND: Epilepsy is a neurological disease characterized by unprovoked seizures in the brain. The recent advances in sensor technologies allow researchers to analyze the collected biological records to improve the treatment of epilepsy. Electroencephalogram (EEG) is the most commonly used biological measurement to effectively capture the abnormalities of different brain areas during the EEG seizures. To avoid manual visual inspection from long-term EEG readings, automatic epileptic EEG seizure detection has become an important research issue in bioinformatics.

RESULTS: We present a multi-context learning approach to automatically detect EEG seizures by incorporating a feature fusion strategy. We generate EEG scalogram sequences from the EEG records by utilizing waveform transform to describe the frequency content over time. We propose a multi-stage unsupervised model that integrates the features extracted from the global handcrafted engineering, channel-wise deep learning, and EEG embeddings, respectively. The learned multi-context features are subsequently merged to train a seizure detector.

CONCLUSIONS: To validate the effectiveness of the proposed approach, extensive experiments against several baseline methods are carried out on two benchmark biological datasets. The experimental results demonstrate that the representative context features from multiple perspectives can be learned by the proposed model, and further improve the performance for the task of EEG seizure detection.}, } @article {pmid30463545, year = {2018}, author = {Liu, L and Yu, Y and Fei, Z and Li, M and Wu, FX and Li, HD and Pan, Y and Wang, J}, title = {An interpretable boosting model to predict side effects of analgesics for osteoarthritis.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {105}, pmid = {30463545}, issn = {1752-0509}, abstract = {BACKGROUND: Osteoarthritis (OA) is the most common disease of arthritis. Analgesics are widely used in the treat of arthritis, which may increase the risk of cardiovascular diseases by 20% to 50% overall.There are few studies on the side effects of OA medication, especially the risk prediction models on side effects of analgesics. In addition, most prediction models do not provide clinically useful interpretable rules to explain the reasoning process behind their predictions. In order to assist OA patients, we use the eXtreme Gradient Boosting (XGBoost) method to balance the accuracy and interpretability of the prediction model.

RESULTS: In this study we used the XGBoost model as a classifier, which is a supervised machine learning method and can predict side effects of analgesics for OA patients and identify high-risk features (RFs) of cardiovascular diseases caused by analgesics. The Electronic Medical Records (EMRs), which were derived from public knee OA studies, were used to train the model. The performance of the XGBoost model is superior to four well-known machine learning algorithms and identifies the risk features from the biomedical literature. In addition the model can provide decision support for using analgesics in OA patients.

CONCLUSION: Compared with other machine learning methods, we used XGBoost method to predict side effects of analgesics for OA patients from EMRs, and selected the individual informative RFs. The model has good predictability and interpretability, this is valuable for both medical researchers and patients.}, } @article {pmid30463540, year = {2018}, author = {Wang, X and Li, Y and He, T and Jiang, X and Hu, X}, title = {Recognition of bacteria named entity using conditional random fields in Spark.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 6}, pages = {106}, pmid = {30463540}, issn = {1752-0509}, abstract = {BACKGROUND: Microbe plays a crucial role in the functional mechanism of an ecosystem. Identification of the interactions among microbes is an important step towards understand the structure and function of microbial communities, as well as of the impact of microbes on human health and disease. Despite the importance of it, there is not a gold-standard dataset of microbial interactions currently. Traditional approaches such as growth and co-culture analysis need to be performed in the laboratory, which are time-consuming and costly. By providing predicted candidate interactions to experimental verification, computational methods are able to alleviate this problem. Mining microbial interactions from mass medical texts is one type of computational methods. Identification of the named entity of bacteria and related entities from the text is the basis for microbial relation extraction. In the previous work, a system of bacteria named entities recognition based on the dictionary and conditional random field was proposed. However, it is inefficient when dealing with large-scale text.

RESULTS: We implemented bacteria named entity recognition on Spark platform and designed experiments for comparison to verify the correctness and validity of the proposed system. The experimental results show that it can achieve higher F-Measure on the comparison of correctness. Moreover, the predicting speed is much faster than the previous version in large-scale biomedical datasets, and the computational efficiency is improved remarkably by about 3.1 to 6.7 times.

CONCLUSIONS: The system for bacteria named entity recognition solves the inefficiency of the previous proposed system on large-scale datasets. The proposed system has good performance in accuracy and scalability.}, } @article {pmid30463532, year = {2018}, author = {Armisén, D and Rajakumar, R and Friedrich, M and Benoit, JB and Robertson, HM and Panfilio, KA and Ahn, SJ and Poelchau, MF and Chao, H and Dinh, H and Doddapaneni, HV and Dugan, S and Gibbs, RA and Hughes, DST and Han, Y and Lee, SL and Murali, SC and Muzny, DM and Qu, J and Worley, KC and Munoz-Torres, M and Abouheif, E and Bonneton, F and Chen, T and Chiang, LM and Childers, CP and Cridge, AG and Crumière, AJJ and Decaras, A and Didion, EM and Duncan, EJ and Elpidina, EN and Favé, MJ and Finet, C and Jacobs, CGC and Cheatle Jarvela, AM and Jennings, EC and Jones, JW and Lesoway, MP and Lovegrove, MR and Martynov, A and Oppert, B and Lillico-Ouachour, A and Rajakumar, A and Refki, PN and Rosendale, AJ and Santos, ME and Toubiana, W and van der Zee, M and Vargas Jentzsch, IM and Lowman, AV and Viala, S and Richards, S and Khila, A}, title = {The genome of the water strider Gerris buenoi reveals expansions of gene repertoires associated with adaptations to life on the water.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {832}, pmid = {30463532}, issn = {1471-2164}, support = {U54 HG003273//National Human Genome Research Institute (US)/ ; SFB 680//Deutsche Forschungsgemeinschaft (DE)/ ; U54 HG003273/HG/NHGRI NIH HHS/United States ; PA 2044/1-1//Deutsche Forschungsgemeinschaft (DE)/ ; 616346//European Research Council/International ; }, abstract = {BACKGROUND: Having conquered water surfaces worldwide, the semi-aquatic bugs occupy ponds, streams, lakes, mangroves, and even open oceans. The diversity of this group has inspired a range of scientific studies from ecology and evolution to developmental genetics and hydrodynamics of fluid locomotion. However, the lack of a representative water strider genome hinders our ability to more thoroughly investigate the molecular mechanisms underlying the processes of adaptation and diversification within this group.

RESULTS: Here we report the sequencing and manual annotation of the Gerris buenoi (G. buenoi) genome; the first water strider genome to be sequenced thus far. The size of the G. buenoi genome is approximately 1,000 Mb, and this sequencing effort has recovered 20,949 predicted protein-coding genes. Manual annotation uncovered a number of local (tandem and proximal) gene duplications and expansions of gene families known for their importance in a variety of processes associated with morphological and physiological adaptations to a water surface lifestyle. These expansions may affect key processes associated with growth, vision, desiccation resistance, detoxification, olfaction and epigenetic regulation. Strikingly, the G. buenoi genome contains three insulin receptors, suggesting key changes in the rewiring and function of the insulin pathway. Other genomic changes affecting with opsin genes may be associated with wavelength sensitivity shifts in opsins, which is likely to be key in facilitating specific adaptations in vision for diverse water habitats.

CONCLUSIONS: Our findings suggest that local gene duplications might have played an important role during the evolution of water striders. Along with these findings, the sequencing of the G. buenoi genome now provides us the opportunity to pursue exciting research opportunities to further understand the genomic underpinnings of traits associated with the extreme body plan and life history of water striders.}, } @article {pmid30463525, year = {2018}, author = {Toju, H and Sato, H and Yamamoto, S and Tanabe, AS}, title = {Structural diversity across arbuscular mycorrhizal, ectomycorrhizal, and endophytic plant-fungus networks.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {292}, pmid = {30463525}, issn = {1471-2229}, support = {26711026//Japan Society for the Promotion of Science/ ; JPMJPR16Q6//Precursory Research for Embryonic Science and Technology/ ; GS014//Cabinet Office, Government of Japan/ ; }, mesh = {Ecosystem ; Japan ; Mycorrhizae/*physiology ; Plants/*microbiology ; *Symbiosis ; }, abstract = {BACKGROUND: Below-ground linkage between plant and fungal communities is one of the major drivers of terrestrial ecosystem dynamics. However, we still have limited knowledge of how such plant-fungus associations vary in their community-scale properties depending on fungal functional groups and geographic locations.

METHODS: By compiling a high-throughput sequencing dataset of root-associated fungi in eight forests along the Japanese Archipelago, we performed a comparative analysis of arbuscular mycorrhizal, ectomycorrhizal, and saprotrophic/endophytic associations across a latitudinal gradient from cool-temperate to subtropical regions.

RESULTS: In most of the plant-fungus networks analyzed, host-symbiont associations were significantly specialized but lacked "nested" architecture, which has been commonly reported in plant-pollinator and plant-seed disperser networks. In particular, the entire networks involving all functional groups of plants and fungi and partial networks consisting of ectomycorrhizal plant and fungal species/taxa displayed "anti-nested" architecture (i.e., negative nestedness scores) in many of the forests examined. Our data also suggested that geographic factors affected the organization of plant-fungus network structure. For example, the southernmost subtropical site analyzed in this study displayed lower network-level specificity of host-symbiont associations and higher (but still low) nestedness than northern localities.

CONCLUSIONS: Our comparative analyses suggest that arbuscular mycorrhizal, ectomycorrhizal, and saprotrophic/endophytic plant-fungus associations often lack nested network architecture, while those associations can vary, to some extent, in their community-scale properties along a latitudinal gradient. Overall, this study provides a basis for future studies that will examine how different types of plant-fungus associations collectively structure terrestrial ecosystems.}, } @article {pmid30463523, year = {2018}, author = {Sui, X and Wu, Q and Chang, W and Fan, X and Song, F}, title = {Proteomic analysis of the response of Funnelifor mismosseae/Medicago sativa to atrazine stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {289}, pmid = {30463523}, issn = {1471-2229}, support = {31570635//National Natural Science Foundation of China/ ; 31500431//National Natural Science Foundation of China/ ; 31270535//National Natural Science Foundation of China/ ; JC201306//Outstanding Youth Science Foundation of Heilongjiang Province/ ; }, mesh = {Atrazine/metabolism/*toxicity ; Biodegradation, Environmental ; Glomeromycota/drug effects/*metabolism ; Herbicides/metabolism/*toxicity ; Medicago sativa/drug effects/*metabolism/microbiology ; Mycorrhizae/drug effects/*metabolism ; Plant Proteins/metabolism ; Proteome/*drug effects ; Soil Pollutants/metabolism/*toxicity ; Symbiosis ; }, abstract = {BACKGROUND: Arbuscular mycorrhizal (AM) fungi form symbiotic associations with host plants can protect host plants against diverse biotic and abiotic stresses, and promote biodegradation of various contaminants. However, the molecular mechanisms of how the arbuscular mycorrhizal fungi and host plant association on atrazine stress were still poorly understood. To better characterize how arbuscular mycorrhizal fungi and host plant interactions increase atrazine stress, we performed physiological and proteomic analysis of Funneliformis mosseae (mycorrhizal fungi) and Medicago sativa (alfalfa) association under atrazine stress.

RESULTS: The results showed that in the Arbuscular mycorrhizal, protective enzymes were up regulated and the malondialdehyde content increased relative to those of non-mycorrhizal M.sativa. We also examined the atrazine degradation rates within the nutrient solution, and a 44.43% reduction was observed with the mycorrhizal M.sativa, with 30.83% of the reduction attributed to F. mosseae. The accumulation content in root and stem of mycorrhizal M.sativa were obviously increased 11.89% and 16.33% than those of non- mycorrhizal M.sativa. The activity of PPO, POD, CAT and SOD in mycorrhizal M.sativa were obviously higher than non mycorrhizal M.sativa under atrazine stess. We identified differential root proteins using isobaric tags for relative and absolute quantization coupled with liquid chromatography-mass spectrometry, with 533 proteins identified (276 unregulated and 257 downregulated). The differentially expressed proteins were further examined using GO, BLAST comparisons, and a literature inquiry and were classified into the categories of atrazine degradation (37.1%); atrazine stress response (28.6%); plant immune responses (14.3%); translation, synthesis, and processing (10%); and signal transduction and biological processes (10%). Furthermore, we identified glycosyl transferase, glutathione S-transferase, laccase, cytochrome P450 monooxygenase, peroxidase, and other proteins closely related to the degradation process.

CONCLUSIONS: Mycorrhizal Medicago showed improved atrazine degradation within the culturing medium and increased atrazine enrichment in the roots and stems. Additionally, AMF increased the plant root response to atrazine, with relevant enzymes up regulated and toxic effects alleviated. Overall, the findings of this study show that AMF played an important role in easing atrazine stress in plants and contributed to atrazine remediation and further contributed to the understanding of the molecular mechanism associated with atrazine stresses and potential mycorrhizal contributions in M.sativa.}, } @article {pmid30463521, year = {2018}, author = {Xue, H and Wang, S and Yao, JL and Deng, CH and Wang, L and Su, Y and Zhang, H and Zhou, H and Sun, M and Li, X and Yang, J}, title = {Chromosome level high-density integrated genetic maps improve the Pyrus bretschneideri 'DangshanSuli' v1.0 genome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {833}, pmid = {30463521}, issn = {1471-2164}, support = {CAAS-ASTIP//the Agricultural Science and Technology Innovation Program/ ; CAAS-XTCX2016017005//the Agricultural Science and Technology Innovation Program/ ; CARS-28//the Earmarked Fund for China Agriculture Research System/ ; 1610192017709//the Central Public-interest Scientific Institution Basal Research Fund/ ; 172102110244//the Science-Technology Project of Henan Province/ ; }, abstract = {BACKGROUND: Chromosomal level reference genomes provide a crucial foundation for genomics research such as genome-wide association studies (GWAS) and whole genome selection. The chromosomal-level sequences of both the European (Pyrus communis) and Chinese (P. bretschneideri) pear genomes have not been published in public databases so far.

RESULTS: To anchor the scaffolds of P. bretschneideri 'DangshanSuli' (DS) v1.0 genome into pseudo-chromosomes, two genetic maps (MH and YM maps) were constructed using half sibling populations of Chinese pear crosses, 'Mantianhong' (MTH) × 'Hongxiangsu' (HXS) and 'Yuluxiang' (YLX) × MTH, from 345 and 162 seedlings, respectively, which were prepared for SNP discovery using genotyping-by-sequencing (GBS) technology. The MH and YM maps, each with 17 linkage groups (LGs), were constructed from 2606 and 2489 SNP markers and spanned 1847 and 1668 cM, respectively, with average marker intervals of 0.7. The two maps were further merged with a previously published genetic map (BD) based on the cross 'Bayuehong' (BYH) × 'Dangshansuli' (DS) to build a new integrated MH-YM-BD map. By using 7757 markers located on the integrated MH-YM-BD map, 898 scaffolds (400.57 Mb) of the DS v1.0 assembly were successfully anchored into 17 pseudo-chromosomes, accounting for 78.8% of the assembled genome size. About 88.31% of them (793 scaffolds) were directionally anchored with two or more markers on the pseudo-chromosomes. Furthermore, the errors in each pseudo-chromosome (especially 1, 5, 7 and 11) were manually corrected and pseudo-chromosomes 1, 5 and 7 were extended by adding 19, 12 and 14 scaffolds respectively in the newly constructed DS v1.1 genome. Synteny analyses revealed that the DS v1.1 genome had high collinearity with the apple genome, and the homologous fragments between pseudo-chromosomes were similar to those found in previous studies. Moreover, the red-skin trait of Asian pear was mapped to an identical locus as identified previously.

CONCLUSIONS: The accuracy of DS v1.1 genome was improved by using larger mapping populations and merged genetic map. With more than 400 MB anchored to 17 pseudo-chromosomes, the new DS v1.1 genome provides a critical tool that is essential for studies of pear genetics, genomics and molecular breeding.}, } @article {pmid30463514, year = {2018}, author = {Tian, L and Liu, H and Ren, L and Ku, L and Wu, L and Li, M and Wang, S and Zhou, J and Song, X and Zhang, J and Dou, D and Liu, H and Tang, G and Chen, Y}, title = {MicroRNA 399 as a potential integrator of photo-response, phosphate homeostasis, and sucrose signaling under long day condition.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {290}, pmid = {30463514}, issn = {1471-2229}, support = {2016YFD0101001//The National Key Research and Development Program of China/ ; 31371628//National Natural Science Foundation of China/ ; }, mesh = {Arabidopsis/genetics/growth & development/*physiology ; Homeostasis/genetics ; MicroRNAs/biosynthesis ; Photoperiod ; Plant Leaves/metabolism ; RNA, Plant/biosynthesis/*physiology ; Signal Transduction ; Sucrose/*metabolism ; Zea mays/genetics/growth & development/*physiology ; }, abstract = {BACKGROUND: Photoperiod-sensitivity is a critical endogenous regulatory mechanism for plant growth and development under specific environmental conditions, while phosphate and sucrose signaling processes play key roles in cell growth and organ initiation. MicroRNA399 is phosphate-responsive, but, whether it has roles in other metabolic processes remains unknown.

RESULTS: MicroRNA399 was determined to be sucrose-responsive through a microRNA array assay. High levels of sucrose inhibited the accumulation of microRNA399 family under phosphate starvation conditions in Arabidopsis thaliana. Similarly, exogenous sucrose supplementation also reduced microRNA399 expression in maize at developmental transition stages. RNA sequencing of a near-isogenic line(photoperiod-sensitive) line and its recurrent parent Huangzao4, a photoperiod-insensitive line, was conducted at various developmental stages. Members of microRNA399 family were down-regulated under long-day conditions in the photoperiod-sensitive near-isogenic line that accumulated more sucrose in vivo compared with the control line Huangzao4.

CONCLUSION: MicroRNA399s may play central roles in the integration of sucrose sensing and photoperiodic responses under long day conditions in maize.}, } @article {pmid30463513, year = {2018}, author = {Lemée, JM and Clavreul, A and Aubry, M and Com, E and de Tayrac, M and Mosser, J and Menei, P}, title = {Integration of transcriptome and proteome profiles in glioblastoma: looking for the missing link.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {13}, pmid = {30463513}, issn = {1471-2199}, abstract = {BACKGROUND: Glioblastoma (GB) is the most common and aggressive tumor of the brain. Genotype-based approaches and independent analyses of the transcriptome or the proteome have led to progress in understanding the underlying biology of GB. Joint transcriptome and proteome profiling may reveal new biological insights, and identify pathogenic mechanisms or therapeutic targets for GB therapy. We present a comparison of transcriptome and proteome data from five GB biopsies (TZ) vs their corresponding peritumoral brain zone (PBZ). Omic analyses were performed using RNA microarray chips and the isotope-coded protein label method (ICPL).

RESULTS: As described in other cancers, we found a poor correlation between transcriptome and proteome data in GB. We observed only two commonly deregulated mRNAs/proteins (neurofilament light polypeptide and synapsin 1) and 12 altered biological processes; they are related to cell communication, synaptic transmission and nervous system processes. This poor correlation may be a consequence of the techniques used to produce the omic profiles, the intrinsic properties of mRNA and proteins and/or of cancer- or GB-specific phenomena. Of interest, the analysis of the transcription factor binding sites present upstream from the open reading frames of all altered proteins identified by ICPL method shows a common binding site for the topoisomerase I and p53-binding protein TOPORS. Its expression was observed in 7/11 TZ samples and not in PBZ. Some findings suggest that TOPORS may function as a tumor suppressor; its implication in gliomagenesis should be examined in future studies.

CONCLUSIONS: In this study, we showed a low correlation between transcriptome and proteome data for GB samples as described in other cancer tissues. We observed that NEFL, SYN1 and 12 biological processes were deregulated in both the transcriptome and proteome data. It will be important to analyze more specifically these processes and these two proteins to allow the identification of new theranostic markers or potential therapeutic targets for GB.}, } @article {pmid30463511, year = {2018}, author = {Chattopadhyay, S and Chi, PB and Minin, VN and Berg, DE and Sokurenko, EV}, title = {Recombination-independent rapid convergent evolution of the gastric pathogen Helicobacter pylori.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {835}, pmid = {30463511}, issn = {1471-2164}, abstract = {BACKGROUND: Helicobacter pylori is a human stomach pathogen, naturally-competent for DNA uptake, and prone to homologous recombination. Extensive homoplasy (i.e., phylogenetically-unlinked identical variations) observed in H. pylori genes is considered a hallmark of such recombination. However, H. pylori also exhibits a high mutation rate. The relative adaptive role of homologous recombination and mutation in species diversity is a highly-debated issue in biology. Recombination results in homoplasy. While convergent mutation can also account for homoplasy, its contribution is thought to be minor. We demonstrate here that, contrary to dogma, convergent mutation is a key contributor to Helicobacter pylori homoplasy, potentially driven by adaptive evolution of proteins.

RESULTS: Our present genome-wide analysis shows that homoplastic nonsynonymous (amino acid replacement) changes are not typically accompanied by homoplastic synonymous (silent) variations. Moreover, the majority of the codon positions with homoplastic nonsynonymous changes also contain different (i.e. non-homoplastic) nonsynonymous changes arising from mutation only. This indicates that, to a considerable extent, nonsynonymous homoplasy is due to convergent mutations. High mutation rate or limited availability of evolvable sites cannot explain this excessive convergence, as suggested by our simulation studies. Rather, the genes with convergent mutations are overrepresented in distinct functional categories, suggesting possible selective responses to conditions such as distinct micro-niches in single hosts, and to differences in host genotype, physiology, habitat and diet.

CONCLUSIONS: We propose that mutational convergence is a key player in H. pylori's adaptation and extraordinary persistence in human hosts. High frequency of mutational convergence could be due to saturation of evolvable sites capable of responding to selection pressures, while the number of mutable residues is far from saturation. We anticipate a similar scenario of mutational vs. recombinational genome dynamics or plasticity for other naturally competent microbes where strong positive selection could favor frequent convergent mutations in adaptive protein evolution.}, } @article {pmid30463510, year = {2018}, author = {Dalto, DB and Tsoi, S and Dyck, MK and Matte, JJ}, title = {Gene ontology analysis of expanded porcine blastocysts from gilts fed organic or inorganic selenium combined with pyridoxine.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {836}, pmid = {30463510}, issn = {1471-2164}, abstract = {BACKGROUND: Gene ontology analysis using the microarray database generated in a previous study by this laboratory was used to further evaluate how maternal dietary supplementation with pyridoxine combined with different sources of selenium (Se) affected global gene expression of expanded porcine blastocysts. Data were generated from 18 gilts randomly assigned to one of three experimental diets (n = 6 per treatment): i) basal diet without supplemental Se or pyridoxine (CONT); ii) CONT + 0.3 mg/kg of Na-selenite and 10 mg/kg of HCl-pyridoxine (MSeB610); and iii) CONT + 0.3 mg/kg of Se-enriched yeast and 10 mg/kg of HCl-pyridoxine (OSeB610). All gilts were inseminated at their fifth post-pubertal estrus and euthanized 5 days later for embryo harvesting. Differential gene expression between MSeB610 vs CONT, OSeB610 vs CONT and OSeB610 vs MSeB610 was performed using a porcine embryo-specific microarray.

RESULTS: There were 559, 2458, and 1547 differentially expressed genes for MSeB610 vs CONT, OSeB610 vs CONT and OSeB610 vs MSeB610, respectively. MSeB610 vs CONT stimulated 13 biological processes with a strict effect on RNA binding and translation initiation. OSeB610 vs CONT and OSeB610 vs MSeB610 impacted 188 and 66 biological processes, respectively, with very similar effects on genome stability, ceramide biosynthesis, protein trafficking and epigenetic events. The stimulation of genes related with these processes was confirmed by quantitative real-time RT-PCR.

CONCLUSIONS: Gene expression of embryos from OSeB610 supplemented gilts was more impacted than those from MSeB610 supplemented gilts. Whereas maternal OSeB610 supplementation influenced crucial aspects of embryo development, maternal MSeB610 supplementation was restricted to binding activity.}, } @article {pmid30463509, year = {2018}, author = {Altenbach, SB and Chang, HC and Simon-Buss, A and Jang, YR and Denery-Papini, S and Pineau, F and Gu, YQ and Huo, N and Lim, SH and Kang, CS and Lee, JY}, title = {Towards reducing the immunogenic potential of wheat flour: omega gliadins encoded by the D genome of hexaploid wheat may also harbor epitopes for the serious food allergy WDEIA.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {291}, pmid = {30463509}, issn = {1471-2229}, support = {RDA PJ012458//National Institute of Agricultural Science/ ; RDA PJ013149//Next-Generation BioGreen 21 Program/ ; RDA PJ013159//Next-Generation BioGreen 21 Program/ ; Project 5325-43000-028-00D//USDA Agricultural Research Service Research/ ; }, mesh = {Allergens/genetics/*immunology ; Chromosome Mapping ; Chromosomes, Plant ; Electrophoresis, Gel, Two-Dimensional ; Epitopes/genetics/immunology ; *Flour ; Genome, Plant ; Gliadin/genetics/*immunology ; Humans ; Immunoglobulin E/immunology ; Mass Spectrometry ; Mutation ; Plant Breeding ; Polyploidy ; Triticum/genetics/*immunology ; Wheat Hypersensitivity/*immunology ; }, abstract = {BACKGROUND: Omega-5 gliadins are a group of highly repetitive gluten proteins in wheat flour encoded on the 1B chromosome of hexaploid wheat. These proteins are the major sensitizing allergens in a severe form of food allergy called wheat-dependent exercise-induced anaphylaxis (WDEIA). The elimination of omega-5 gliadins from wheat flour through biotechnology or breeding approaches could reduce the immunogenic potential and adverse health effects of the flour.

RESULTS: A mutant line missing low-molecular weight glutenin subunits encoded at the Glu-B3 locus was selected previously from a doubled haploid population generated from two Korean wheat cultivars. Analysis of flour from the mutant line by 2-dimensional gel electrophoresis coupled with tandem mass spectrometry revealed that the omega-5 gliadins and several gamma gliadins encoded by the closely linked Gli-B1 locus were also missing as a result of a deletion of at least 5.8 Mb of chromosome 1B. Two-dimensional immunoblot analysis of flour proteins using sera from WDEIA patients showed reduced IgE reactivity in the mutant relative to the parental lines due to the absence of the major omega-5 gliadins. However, two minor proteins showed strong reactivity to patient sera in both the parental and the mutant lines and also reacted with a monoclonal antibody against omega-5 gliadin. Analysis of the two minor reactive proteins by mass spectrometry revealed that both proteins correspond to omega-5 gliadin genes encoded on chromosome 1D that were thought previously to be pseudogenes.

CONCLUSIONS: While breeding approaches can be used to reduce the levels of the highly immunogenic omega-5 gliadins in wheat flour, these approaches are complicated by the genetic linkage of different classes of gluten protein genes and the finding that omega-5 gliadins may be encoded on more than one chromosome. The work illustrates the importance of detailed knowledge about the genomic regions harboring the major gluten protein genes in individual wheat cultivars for future efforts aimed at reducing the immunogenic potential of wheat flour.}, } @article {pmid30463508, year = {2018}, author = {Dempsey, J and Zhang, A and Cui, JY}, title = {Coordinate regulation of long non-coding RNAs and protein-coding genes in germ-free mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {834}, pmid = {30463508}, issn = {1471-2164}, support = {T32 ES007032//National Institutes of Health/ ; T32 ES007032/ES/NIEHS NIH HHS/United States ; R01 ES019487/ES/NIEHS NIH HHS/United States ; R01 GM111381/GM/NIGMS NIH HHS/United States ; P30 ES007033/ES/NIEHS NIH HHS/United States ; ES019487//National Institutes of Health/ ; R01 ES025708/ES/NIEHS NIH HHS/United States ; GM111381//National Institutes of Health/ ; P30 ES0007033//National Institutes of Health/ ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) are increasingly recognized as regulators of tissue-specific cellular functions and have been shown to regulate transcriptional and translational processes, acting as signals, decoys, guides, and scaffolds. It has been suggested that some lncRNAs act in cis to regulate the expression of neighboring protein-coding genes (PCGs) in a mechanism that fine-tunes gene expression. Gut microbiome is increasingly recognized as a regulator of development, inflammation, host metabolic processes, and xenobiotic metabolism. However, there is little known regarding whether the gut microbiome modulates lncRNA gene expression in various host metabolic organs. The goals of this study were to 1) characterize the tissue-specific expression of lncRNAs and 2) identify and annotate lncRNAs differentially regulated in the absence of gut microbiome.

RESULTS: Total RNA was isolated from various tissues (liver, duodenum, jejunum, ileum, colon, brown adipose tissue, white adipose tissue, and skeletal muscle) from adult male conventional and germ-free mice (n = 3 per group). RNA-Seq was conducted and reads were mapped to the mouse reference genome (mm10) using HISAT. Transcript abundance and differential expression was determined with Cufflinks using the reference databases NONCODE 2016 for lncRNAs and UCSC mm10 for PCGs. Although the constitutive expression of lncRNAs was ubiquitous within the enterohepatic (liver and intestine) and the peripheral metabolic tissues (fat and muscle) in conventional mice, differential expression of lncRNAs by lack of gut microbiota was highly tissue specific. Interestingly, the majority of gut microbiota-regulated lncRNAs were in jejunum. Most lncRNAs were co-regulated with neighboring PCGs. STRING analysis showed that differentially expressed PCGs in proximity to lncRNAs form tissue-specific networks, suggesting that lncRNAs may interact with gut microbiota/microbial metabolites to regulate tissue-specific functions.

CONCLUSIONS: This study is among the first to demonstrate that gut microbiota critically regulates the expression of lncRNAs not only locally in intestine but also remotely in other metabolic organs, suggesting that common transcriptional machinery may be shared to transcribe lncRNA-PCG pairs, and lncRNAs may interact with PCGs to regulate tissue-specific pathways.}, } @article {pmid30463507, year = {2018}, author = {Shunmugam, ASK and Bollina, V and Dukowic-Schulze, S and Bhowmik, PK and Ambrose, C and Higgins, JD and Pozniak, C and Sharpe, AG and Rozwadowski, K and Kagale, S}, title = {MeioCapture: an efficient method for staging and isolation of meiocytes in the prophase I sub-stages of meiosis in wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {293}, pmid = {30463507}, issn = {1471-2229}, support = {CTAG2//Genome Canada/ ; IOS-1025881 and IOS-1546792//National Science Foundation/ ; BB/M014908/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Separation/*methods ; Flowers/cytology/ultrastructure ; *Meiotic Prophase I ; *Plant Cells/ultrastructure ; Triticum/*cytology ; }, abstract = {BACKGROUND: Molecular analysis of meiosis has been hindered by difficulties in isolating high purity subpopulations of sporogenous cells representing the succeeding stages of meiosis. Isolation of purified male meiocytes from defined meiotic stages is crucial in discovering meiosis specific genes and associated regulatory networks.

RESULTS: We describe an optimized method termed MeioCapture for simultaneous isolation of uncontaminated male meiocytes from wheat (Triticum spp.), specifically from the pre-meiotic G2 and the five sub-stages of meiotic prophase I. The MeioCapture protocol builds on the traditional anther squash technique and the capillary collection method, and involves extrusion of intact sporogenous archesporial columns (SACs) containing meiocytes. This improved method exploits the natural meiotic synchrony between anthers of the same floret, the correlation between the length of anthers and meiotic stage, and the occurrence of meiocytes in intact SACs largely free of somatic cells. The main advantage of MeioCapture, compared to previous methods, is that it allows simultaneous collection of meiocytes from different sub-stages of prophase I at a very high level of purity, through correlation of stages with anther sizes. A detailed description is provided for all steps, including the collection of tissue, isolation and size sorting of anthers, extrusion of intact SACs, and staging of meiocytes. Precautions for individual steps throughout the procedure are also provided to facilitate efficient isolation of pure meiocytes. The proof-of-concept was successfully established in wheat, and a light microscopic atlas of meiosis, encompassing all stages from pre-meiosis to telophase II, was developed.

CONCLUSION: The MeioCapture method provides an essential technique to study the molecular basis of chromosome pairing and exchange of genetic information in wheat, leading to strategies for manipulating meiotic recombination frequencies. The method also provides a foundation for similar studies in other crop species.}, } @article {pmid30463505, year = {2018}, author = {Lee, T and Yoon, Y}, title = {Drug repositioning using drug-disease vectors based on an integrated network.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {446}, pmid = {30463505}, issn = {1471-2105}, support = {NRF-2018R1A2B6006223//National Research Foundation of Korea/ ; }, mesh = {Animals ; Computational Biology/*methods ; *Disease Vectors ; Drug Repositioning/*methods ; Gene Expression Regulation/*genetics ; Gene Regulatory Networks/*genetics ; Humans ; }, abstract = {BACKGROUND: Diverse interactions occur between biomolecules, such as activation, inhibition, expression, or repression. However, previous network-based studies of drug repositioning have employed interaction on the binary protein-protein interaction (PPI) network without considering the characteristics of the interactions. Recently, some studies of drug repositioning using gene expression data found that associations between drug and disease genes are useful information for identifying novel drugs to treat diseases. However, the gene expression profiles for drugs and diseases are not always available. Although gene expression profiles of drugs and diseases are available, existing methods cannot use the drugs or diseases, when differentially expressed genes in the profiles are not included in their network.

RESULTS: We developed a novel method for identifying candidate indications of existing drugs considering types of interactions between biomolecules based on known drug-disease associations. To obtain associations between drug and disease genes, we constructed a directed network using protein interaction and gene regulation data obtained from various public databases providing diverse biological pathways. The network includes three types of edges depending on relationships between biomolecules. To quantify the association between a target gene and a disease gene, we explored the shortest paths from the target gene to the disease gene and calculated the types and weights of the shortest paths. For each drug-disease pair, we built a vector consisting of values for each disease gene influenced by the drug. Using the vectors and known drug-disease associations, we constructed classifiers to identify novel drugs for each disease.

CONCLUSION: We propose a method for exploring candidate drugs of diseases using associations between drugs and disease genes derived from a directed gene network instead of gene regulation data obtained from gene expression profiles. Compared to existing methods that require information on gene relationships and gene expression data, our method can be applied to a greater number of drugs and diseases. Furthermore, to validate our predictions, we compared the predictions with drug-disease pairs in clinical trials using the hypergeometric test, which showed significant results. Our method also showed better performance compared to existing methods for the area under the receiver operating characteristic curve (AUC).}, } @article {pmid30463438, year = {2018}, author = {Gassen, J and Bradshaw, HK and Hill, SE}, title = {Mating Effort Predicts Human Menstrual Cycle Frequency.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918812124}, doi = {10.1177/1474704918812124}, pmid = {30463438}, issn = {1474-7049}, abstract = {The human menstrual cycle is characterized by substantial variability both within and between women. Here, we sought to account for such variability by examining whether human menstrual cycle frequency varies as a function of the projected fitness payoffs associated with investment in mating effort. We used structural equation modeling to test the prediction that women whose environmental conditions or life histories favor heavier investment in mating effort would have shorter, more regular cycles. Results supported our hypothesis, revealing that women who project more mating success and have faster life history strategies exhibit greater mating effort and shorter, more regular menstrual cycles. An alternative model that specified cycle frequency as a predictor of mating effort was a poor fit for the data, lending support for the hypothesized directionality of the path between these variables. Together, these results provide some of the first empirical evidence that the length and regularity of the human menstrual cycle may be calibrated to investment in mating effort.}, } @article {pmid30463433, year = {2018}, author = {Zhang, S and Wang, H and Guo, Q}, title = {Sex and Physiological Cycles Affect the Automatic Perception of Attractive Opposite-Sex Faces: A Visual Mismatch Negativity Study.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918812140}, doi = {10.1177/1474704918812140}, pmid = {30463433}, issn = {1474-7049}, abstract = {Facial attractiveness plays important roles in social interaction. Electrophysiological and neuroimaging studies found several brain areas to be differentially responsive to attractive relative to unattractive faces. However, little is known about the time course of the information processing, especially under the unattended condition. Based on a "cross-modal delayed response" paradigm, the present study aimed to explore the automatic mechanism of facial attractiveness processing of females with different physiological cycles and males, respectively, through recording the event-related potentials in response to (un)attractive opposite-sex faces by two experiments. The attractiveness-related visual mismatch negativity (attractiveness vMMN) in posterior scalp distribution was recorded in both the experiments, which indicated that attractive faces could be processed automatically. And high-attractive opposite-sex faces can elicit larger vMMN in males than females in menstrual period in Study 1, but similar as females in ovulatory period in Study 2. Furthermore, by comparison, the latency of attractiveness vMMN in females with the ovulatory period was the longest. These results indicated as follows: (1) Males were more sensitive to attractive female faces, (2) females in ovulatory period were also attracted by the attractive male faces, (3) the long vMMN latency in females during ovulatory period suggested a special reproductive motivation to avoid being tainted by genes, which takes priority over the breeding motivation.}, } @article {pmid30461378, year = {2019}, author = {Abril, AG and Rama, JLR and Feijoo-Siota, L and Calo-Mata, P and Salazar, S and Peix, A and Velázquez, E and Villa, TG}, title = {Bacillus safensis subsp. osmophilus subsp. nov., isolated from condensed milk, and description of Bacillus safensis subsp. safensis subsp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {189-195}, doi = {10.1099/ijsem.0.003126}, pmid = {30461378}, issn = {1466-5034}, abstract = {A bacterial strain, designated BC09T, was isolated from a contaminated sample of condensed milk. Phylogenetic analyses based on 16S rRNA gene sequences placed strain BC09T into the genus Bacillus with its closest relatives being Bacillus safensis and Bacillus australimaris with 100 and 99.9 % similarity, respectively. Analysis of the gyrB gene confirmed the closeness of strain BC09T with respect to the species B. safensis since it presented 97.8 and 95.2 % similarity values, respectively, to the type strains of B. safensis and B. australimaris. DNA-DNA hybridization confirmed these results showing averages of 67 and 56 %, respectively, between strain BC09T and the type strains of B. safensis and B. australimaris. Average nucleotide identity blast values obtained for BC09T compared to the closest relative type strains were 95.7 and 67.6 %, respectively, and predicted DNA-DNA hybridization values were 93.1 and 51.9 %, respectively. However, strain BC09T differs from the type strains of its closest relatives in several phenotypic characteristics. MK-7 was the only menaquinone detected and iso-C15:0 and anteiso-C15:0 were the major fatty acids. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, two unidentified phospholipids, two unidentifed glycolipids, three unidentified lipids and one unidentifed phosphoglycolipid. Meso-diaminopimelic acid was detected in the peptidoglycan. The G+C content was 40.9 mol%. Phylogenetic, chemotaxonomic and phenotypic analyses showed that strain BC09T represents a new subspecies of B. safensis, for which the name Bacillus safensis subsp. osmophilus subsp. nov. is proposed. The type strain is BC09T (=LMG 30124T, =CECT 9344T).}, } @article {pmid30461377, year = {2019}, author = {Sant'Anna, FH and Ambrosini, A and Guella, FL and Porto, RZ and Passaglia, LMP}, title = {Genome-based reclassification of Paenibacillus dauci as a later heterotypic synonym of Paenibacillus shenyangensis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {177-182}, doi = {10.1099/ijsem.0.003127}, pmid = {30461377}, issn = {1466-5034}, abstract = {Paenibacillus shenyangensis and Paenibacillus dauci are Gram-stain-positive, rod-shaped and endospore-forming bacteria originally isolated from soil and carrot samples, respectively, in China. Preliminary comparative genomic analysis showed that these bacteria could constitute a single species. Therefore, in this study, their taxonomic statuses were clarified through distinct genomic metrics and phylogenetic analyses. Paenibacillus shenyangensis A9T and P. dauci H9T presented values of average nucleotide identity (ANI) and its derivative metrics (gANI and OrthoANI) ranging from 97.88 to 98.08 %, and digital DNA-DNA hybridization equal to 89.08 %. Furthermore, the identities of 16S rRNA, gyrB, rpoB, recA and recN genes were all equal or higher than 98.7 %. Phylogenies of these marker genes and the concatenated core proteome were congruent in the sense that P. shenyangensis A9T and P. dauci H9T are the closest type-strains of the genus Paenibacillus. A review of their profiles revealed that these strains do not present pronounced differences at the phenotypic and chemotaxonomic levels. Considering phylogenetic, genomic, phenotypic and chemotaxonomic data, P. dauci should be reclassified as a later heterotypic synonym of P. shenyangensis.}, } @article {pmid30461376, year = {2019}, author = {Dai, X and Shi, K and Wang, X and Fan, J and Wang, R and Zheng, S and Wang, G}, title = {Paenibacillus flagellatus sp. nov., isolated from selenium mineral soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {183-188}, doi = {10.1099/ijsem.0.003125}, pmid = {30461376}, issn = {1466-5034}, abstract = {Strain DXL2T, a Gram-stain-negative, rod-shaped, endospore-forming, motile, aerobic bacterium, was isolated from selenium mineral soil. DXL2T had the highest 16S rRNA gene sequence similarities with those of Paenibacillus ginsengarviGsoil 139T (96.8 %), Paenibacillushemerocallicola DLE-12T (95.5 %) and Paenibacillus hodogayensisSGT (95.4 %). The genome size of DXL2T was 7.24 Mb, containing 6243 predicted protein-coding genes, with a DNA G+C content of 60.2 mol%. DXL2T contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The major cellular fatty acids were anteiso-C15 : 0, iso-C16 : 0 and iso-C15 : 0. The major quinone was menaquinone 7. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two aminophospholipids, an unidentified aminolipid, phosphatidylmethylethanolamine, an unidentified glycolipid and an unidentified phospholipid. Compared with the other strains, DXL2T had a specific phospholipid and a specific aminolipid, it hydrolyzed Tween 40 and could not assimilate potassium gluconate. On the basis of the phenotypic, chemotaxonomic and phylogenetic results, strain DXL2T represents a novel species within the genus Paenibacillus, for which the name Paenibacillusflagellatus sp. nov. is proposed. The type strain is DXL2T (=KCTC 33976T=CCTCC AB 2018054T).}, } @article {pmid30461226, year = {2018}, author = {Wackett, LP}, title = {Microbial degradation of agricultural chemicals: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {718-719}, doi = {10.1111/1758-2229.12715}, pmid = {30461226}, issn = {1758-2229}, } @article {pmid30461157, year = {2018}, author = {James, AK and Kelly, LW and Nelson, CE and Wilbanks, EG and Carlson, CA}, title = {Elevated pCO2 alters marine heterotrophic bacterial community composition and metabolic potential in response to a pulse of phytoplankton organic matter.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14484}, pmid = {30461157}, issn = {1462-2920}, support = {OCE-1041038OCE-12-36905OCE-1538393 OCE-1538428 OCE-1538567//National Science Foundation/ ; OCE-1538428//National Science Foundation/ ; OCE-1538393//National Science Foundation/ ; OCE-1538567//National Science Foundation/ ; OCE-12-36905//National Science Foundation/ ; OCE-1041038//National Science Foundation/ ; NA14OAR4170071//NOAA Office of Sea Grant, Department of Commerce/ ; //Simons Foundation International/ ; //University of California, Santa Barbara/ ; //University of Hawai'i at Mānoa/ ; NA14OAR4170071//Department of Commerce/ ; //University of Hawai'i/ ; //National Oceanic and Atmospheric Administration/ ; //University of California/ ; //Simons Foundation/ ; }, abstract = {Factors that affect the respiration of organic carbon by marine bacteria can alter the extent to which the oceans act as a sink of atmospheric carbon dioxide. We designed seawater dilution experiments to assess the effect of pCO2 enrichment on heterotrophic bacterial community composition and metabolic potential in response to a pulse of phytoplankton-derived organic carbon. Experiments included treatments of elevated (1000 p.p.m.) and low (250 p.p.m.) pCO2 amended with 10 μmol L-1 dissolved organic carbon from Emiliana huxleyi lysates, and were conducted using surface-seawater collected from the South Pacific Subtropical Gyre. To assess differences in community composition and metabolic potential, shotgun metagenomic libraries were sequenced from low and elevated pCO2 treatments collected at the start of the experiment and following exponential growth. Our results indicate bacterial communities changed markedly in response to the organic matter pulse over time and were significantly affected by pCO2 enrichment. Elevated pCO2 also had disproportionate effects on the abundance of sequences related to proton pumps, carbohydrate metabolism, modifications of the phospholipid bilayer, resistance to toxic compounds and conjugative transfer. These results contribute to a growing understanding of the effects of elevated pCO2 on bacteria-mediated carbon cycling during phytoplankton bloom conditions in the marine environment.}, } @article {pmid30461142, year = {2018}, author = {Song, GC and Im, H and Jung, J and Lee, S and Jung, MY and Rhee, SK and Ryu, CM}, title = {Plant growth-promoting archaea trigger induced systemic resistance in Arabidopsis thaliana against Pectobacterium carotovorum and Pseudomonas syringae.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14486}, pmid = {30461142}, issn = {1462-2920}, support = {KGM2111844//Korea Research Institute of Bioscience and Biotechnology/ ; 918017-4//Ministry of Agriculture, Food and Rural Affairs/ ; Woo Jang-Choon Project (PJ01093904)//Rural Development Administration/ ; }, abstract = {Archaea have inhabited the earth for a long period of time and are ubiquitously distributed in diverse environments. However, few studies have focused on the interactions of archaea with other organisms, including eukaryotes such as plants, since it is difficult to cultivate sufficient numbers of archaeal cells for analysis. In this study, we investigated the interaction between soil archaea and Arabidopsis thaliana. We demonstrate for the first time that soil archaea promote plant growth and trigger induced systemic resistance (ISR) against the necrotrophic bacterium Pectobacterium carotovorum subsp. carotovorum SCC1 and biotrophic bacterium Pseudomonas syringae pv. tomato DC3000. Ammonia-oxidizing archaeon Nitrosocosmicus oleophilus MY3 cells clearly colonized the root surface of Arabidopsis plants, and increased resistance against both pathogenic species via the salicylic acid-independent signalling pathway. This mechanism of bacterial resistance resembles that underlying soil bacteria- and fungi-mediated ISR signalling. Additionally, volatile emissions from N. oleophilus MY3 were identified as major archaeal determinants that elicit ISR. Our results lay a foundation for archaea-plant interactions as a new field of research.}, } @article {pmid30461107, year = {2018}, author = {Olito, C and Marshall, DJ}, title = {Releasing small ejaculates slowly increases per-gamete fertilization success in an external fertilizer: Galeolaria caespitosa (Polychaeta: Serpulidae).}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13403}, pmid = {30461107}, issn = {1420-9101}, support = {//Monash University Dean's International Postgraduate Student Scholarship/ ; }, abstract = {The idea that male reproductive strategies evolve primarily in response to sperm competition is almost axiomatic in evolutionary biology. However, externally fertilizing species, especially broadcast spawners, represent a large and taxonomically diverse group that have long challenged predictions from sperm competition theory - broadcast spawning males often release sperm slowly, with weak resource-dependent allocation to ejaculates despite massive investment in gonads. One possible explanation for these counter-intuitive patterns is that male broadcast spawners experience strong natural selection from the external environment during sperm dispersal. Using a manipulative experiment, we examine how male reproductive success in the absence of sperm competition varies with ejaculate size and rate of sperm release, in the broadcast spawning marine invertebrate Galeolaria caespitosa (Polychaeta: Serpulidae). We find that the benefits of Fast or Slow sperm release depend strongly on ejaculate size, but also that the per-gamete fertilization rate decreases precipitously with ejaculate size. Overall, these results suggest that, if males can facultatively adjust ejaculate size, they should slowly release small amounts of sperm. Recent theory for broadcast spawners predicts that sperm competition can also select for Slow release rates. Taken together, our results and theory suggest that selection often favours Slow ejaculate release rates whether males experience sperm competition or not.}, } @article {pmid30460998, year = {2018}, author = {Bergmann, PJ and Morinaga, G}, title = {The convergent evolution of snake-like forms by divergent evolutionary pathways in squamate reptiles.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13651}, pmid = {30460998}, issn = {1558-5646}, support = {IOS-1353703//NSF/ ; 1353703//Division of Integrative Organismal Systems/ ; }, abstract = {Convergent evolution of phenotypes is considered evidence that evolution is deterministic. Establishing if such convergent phenotypes arose through convergent evolutionary pathways is a stronger test of determinism. We studied the evolution of snake-like body shapes in six clades of lizards, each containing species ranging from short-bodied and pentadactyl to long-bodied and limbless. We tested whether body shapes that evolved in each clade were convergent, and whether clades evolved snake-like body shapes following convergent evolutionary pathways. Our analyses showed that indeed species with the same numbers of digits in each clade evolved convergent body shapes. We then compared evolutionary pathways among clades by considering patterns of evolutionary integration and shape of relationship among body parts, patterns of vertebral evolution, and models of digit evolution. We found that all clades elongated their bodies through the addition, not elongation, of vertebrae, and had similar patterns of integration. However, patterns of integration, the body parts that were related by a linear or a threshold model, and patterns of digit evolution differed among clades. These results showed that clades followed different evolutionary pathways. This suggests an important role of historical contingency as opposed to determinism in the convergent evolution of snake-like body shapes.}, } @article {pmid30460993, year = {2019}, author = {Jensen, JD and Payseur, BA and Stephan, W and Aquadro, CF and Lynch, M and Charlesworth, D and Charlesworth, B}, title = {The importance of the Neutral Theory in 1968 and 50 years on: A response to Kern and Hahn 2018.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {111-114}, doi = {10.1111/evo.13650}, pmid = {30460993}, issn = {1558-5646}, abstract = {A recent article reassessing the Neutral Theory of Molecular Evolution claims that it is no longer as important as is widely believed. The authors argue that "the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality." Claiming that "the neutral theory has been overwhelmingly rejected," they propose instead that natural selection is the major force shaping both between-species divergence and within-species variation. Although this is probably a minority view, it is important to evaluate such claims carefully in the context of current knowledge, as inaccuracies can sometimes morph into an accepted narrative for those not familiar with the underlying science. We here critically examine and ultimately reject Kern and Hahn's arguments and assessment, and instead propose that it is now abundantly clear that the foundational ideas presented five decades ago by Kimura and Ohta are indeed correct.}, } @article {pmid30460778, year = {2018}, author = {Zhao, XX and An, XL and Zhu, XC and Jiang, Y and Zhai, YH and Zhang, S and Cai, NN and Tang, B and Li, ZY and Zhang, XM}, title = {Inhibiting transforming growth factor-β signaling regulates in vitro maintenance and differentiation of bovine bone marrow mesenchymal stem cells.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {8}, pages = {406-416}, doi = {10.1002/jez.b.22836}, pmid = {30460778}, issn = {1552-5015}, support = {20150101103JC//Scientific & Technological Developing Project, Jilin Province, China/ ; PCSIRT, No. IRT_16R32//Program for Changjiang Scholars and Innovative Research Team in University, Ministry of Education, China/ ; }, abstract = {Bovine bone marrow mesenchymal stem cells (bBMSC) are potential stem cell source which can be used for multipurpose. However, their application is limited because the in vitro maintenance of these cells is usually accompanied by aging and multipotency losing. Considering transforming growth factor-β (TGF-β) pathway inhibitor Repsox is beneficial for cell reprogramming, here we investigated its impacts on the maintenance and differentiation of bBMSC. The bBMSC were enriched and characterized by morphology, immunofluorescent staining, flow cytometry, and multilineage differentiation. The impacts of Repsox on their proliferation, apoptosis, cell cycle, multipotency, and differentiation were examined by Cell Counting Kit-8 (CCK-8), real-time polymerase chain reaction, induced differentiation and specific staining. The results showed that highly purified cluster of diffrentiation 73+ (CD73 +)/CD90 + /CD105 + /CD34 - /CD45 - bBMSC with adipogenic, osteogenic, and chondrogenic differentiation capacities were enriched. Repsox treatments (5 μM, 48 hr) enhanced the messenger RNA mRNA levels of the proliferation gene (telomerase reverse transcriptase [ TERT]; basic fibroblast growth factor [ bFGF]), apoptosis-related gene (bax and Bcl2), antiapoptosis ratio (Bcl2/bax), and pluripotency marker gene (Oct4, Sox2, and Nanog), instead of changing the cell cycle, in bBMSC. Repsox treatments also enhanced the osteogenic differentiation but attenuated the chondrogenic differentiation of bBMSC, concomitant with decreased Smad2 and increased Smad3/4 expressions in TGF-β pathway. Collectively, inhibiting TGF-β/Smad signaling by Repsox regulates the in vitro maintenance and differentiation of bBMSC.}, } @article {pmid30460750, year = {2018}, author = {Oettler, J and Platschek, T and Schmidt, C and Rajakumar, R and Favé, MJ and Khila, A and Heinze, J and Abouheif, E}, title = {Interruption points in the wing gene regulatory network underlying wing polyphenism evolved independently in male and female morphs in Cardiocondyla ants.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {}, number = {}, pages = {}, doi = {10.1002/jez.b.22834}, pmid = {30460750}, issn = {1552-5015}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; He1623/31//Deutsche Forschungsgemeinschaft/ ; He 1623/23//Deutsche Forschungsgemeinschaft/ ; //Konrad Lorenz Institute/ ; //Centre de Coopération Universitaire Franco-Bavarois/ ; }, abstract = {Wing polyphenism in ants, which produces a winged female queen caste and a wingless female worker caste, evolved approximately 150 million years ago and has been key to the remarkable success of ants. Approximately 20 million years ago, the myrmicine ant genus Cardiocondyla evolved an additional wing polyphenism among males producing two male morphs: wingless males that fight to enhance mating success and winged males that disperse. Here we show that interruption of rudimentary wing-disc development in larvae of the ant Cardiocondyla obscurior occurs further downstream in the network in wingless males as compared with wingless female workers. This pattern is corroborated in C. kagutsuchi, a species from a different clade within the genus, indicating that late interruption of wing development in males is conserved across Cardiocondyla. Therefore, our results show that the novel male wing polyphenism was not developmentally constrained by the pre-existing female wing polyphenism and evolved through independent alteration of interruption points in the wing gene network. Furthermore, a comparison of adult morphological characters in C. obscurior reveals that developmental trajectories lead to similar morphological trait integration between winged and wingless females, but dramatically different integration between winged and wingless males. This suggests that the alternative sex-specific developmental routes to achieve winglessness in the genus Cardiocondyla may have evolved through different selection regimes acting on wingless males and females.}, } @article {pmid30459847, year = {2018}, author = {Zhu, L and Deng, C and Zhao, X and Ding, J and Huang, H and Zhu, S and Wang, Z and Qin, S and Ding, Y and Lu, G and Yang, Z}, title = {Endangered Père David's deer genome provides insights into population recovering.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {2040-2053}, pmid = {30459847}, issn = {1752-4571}, abstract = {The Milu (Père David's deer, Elaphurus davidianus) were once widely distributed in the swamps (coastal areas to inland areas) of East Asia. The dramatic recovery of the Milu population is now deemed a classic example of how highly endangered animal species can be rescued. However, the molecular mechanisms that underpinned this population recovery remain largely unknown. Here, different approaches (genome sequencing, resequencing, and salinity analysis) were utilized to elucidate the aforementioned molecular mechanisms. The comparative genomic analyses revealed that the largest recovered Milu population carries extensive genetic diversity despite an extreme population bottleneck. And the protracted inbreeding history might have facilitated the purging of deleterious recessive alleles. Seventeen genes that are putatively related to reproduction, embryonic (fatal) development, and immune response were under high selective pressure. Besides, SCNN1A, a gene involved in controlling reabsorption of sodium in the body, was positively selected. An additional 29 genes were also observed to be positively selected, which are involved in blood pressure regulation, cardiovascular development, cholesterol regulation, glycemic control, and thyroid hormone synthesis. It is possible that these genetic adaptations were required to buffer the negative effects commonly associated with a high-salt diet. The associated genetic adaptions are likely to have enabled increased breeding success and fetal survival. The future success of Milu population management might depend on the successful reintroduction of the animal to historically important distribution regions.}, } @article {pmid30459846, year = {2018}, author = {Massatti, R and Prendeville, HR and Larson, S and Richardson, BA and Waldron, B and Kilkenny, FF}, title = {Population history provides foundational knowledge for utilizing and developing native plant restoration materials.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {2025-2039}, pmid = {30459846}, issn = {1752-4571}, abstract = {A species' population structure and history are critical pieces of information that can help guide the use of available native plant materials in restoration treatments and decide what new native plant materials should be developed to meet future restoration needs. In the western United States, Pseudoroegneria spicata (bluebunch wheatgrass; Poaceae) is an important component of grassland and shrubland plant communities and commonly used for restoration due to its drought resistance and competitiveness with exotic weeds. We used next-generation sequencing data to investigate the processes that shaped P. spicata's geographic pattern of genetic variation across the Intermountain West. Pseudoroegneria spicata's genetic diversity is partitioned into populations that likely differentiated since the Last Glacial Maximum. Adjacent populations display varying magnitudes of historical gene flow, with migration rates ranging from multiple migrants per generation to multiple generations per migrant. When considering the commercial germplasm sources available for restoration, genetic identities remain representative of the wildland localities from which germplasm sources were originally developed, and they maintain high levels of heterozygosity and nucleotide diversity. However, the commercial germplasm sources represent a small fraction of the overall genetic diversity of P. spicata in the Intermountain West. Given the low migration rates and long divergence times between some pairs of P. spicata populations, using commercial germplasm sources could facilitate undesirable restoration outcomes when used in certain geographic areas, even if the environment in which the commercial materials thrive is similar to that of the restoration site. As such, population structure and history can be used to provide guidance on what geographic areas may need additional native plant materials so that restoration efforts support species and community resilience and improve outcomes.}, } @article {pmid30459845, year = {2018}, author = {MacIvor, JS and Sookhan, N and Arnillas, CA and Bhatt, A and Das, S and Yasui, SE and Xie, G and Cadotte, MW}, title = {Manipulating plant phylogenetic diversity for green roof ecosystem service delivery.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {2014-2024}, pmid = {30459845}, issn = {1752-4571}, abstract = {Plant species and functional trait diversity have each been shown to improve green roof services. Species and trait differences that contribute to ecosystem services are the product of past evolutionary change and phylogenetic diversity (PD), which quantifies the relatedness among species within a community. In this study, we present an experimental framework to assess the contribution of plant community PD for green roof ecosystem service delivery, and data from one season that support our hypotheses that PD would be positively correlated with two services: building cooling and rainwater management. Using 28 plant species in 12 families, we created six community combinations with different levels of PD. Each of these communities was replicated at eight green roofs along an elevation gradient, as well as a ground level control. We found that the minimum and mean roof temperature decreased with increasing PD in the plant community. Increasing PD also led to an increase in the volume of rainwater captured, but not the proportion of water lost via evapotranspiration 48 hr following the rain event. Our findings suggest that considering these evolutionary relationships could improve functioning of green infrastructure and we recommend that understanding how to make PD (and other measures of diversity) serviceable for plant selection by practitioners will improve the effectiveness of design and ecosystem service delivery. Lastly, since no two green roof sites are the same and can vary tremendously in microclimate conditions, our study illustrates the importance of including multiple independent sites in studies of green roof performance.}, } @article {pmid30459844, year = {2018}, author = {Bacigalupe, LD and Gaitán-Espitia, JD and Barria, AM and Gonzalez-Mendez, A and Ruiz-Aravena, M and Trinder, M and Sinervo, B}, title = {Natural selection on plasticity of thermal traits in a highly seasonal environment.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {2004-2013}, pmid = {30459844}, issn = {1752-4571}, abstract = {For ectothermic species with broad geographical distributions, latitudinal/altitudinal variation in environmental temperatures (averages and extremes) is expected to shape the evolution of physiological tolerances and the acclimation capacity (i.e., degree of phenotypic plasticity) of natural populations. This can create geographical gradients of selection in which environments with greater thermal variability (e.g., seasonality) tend to favor individuals that maximize performance across a broader range of temperatures compared to more stable environments. Although thermal acclimation capacity plays a fundamental role in this context, it is unknown whether natural selection targets this trait in natural populations. Additionally, understanding whether and how selection acts on thermal physiological plasticity is also highly relevant to climate change and biological conservation. Here, we addressed such an important gap in our knowledge in the northernmost population of the four-eyed frog, Pleurodema thaul. We measured plastic responses of critical thermal limits for activity, behavioral thermal preference, and thermal sensitivity of metabolism to acclimation at 10 and 20°C. We monitored survival during three separate recapture efforts and used mark-recapture integrated into an information-theoretic approach to evaluate the relationship between survivals as a function of the plasticity of thermal traits. Overall, we found no evidence that thermal acclimation in this population is being targeted by directional selection, although there might be signals of selection on individual traits. According to the most supported models, survival increased in individuals with higher tolerance to cold when cold-acclimated, probably because daily low extremes are frequent during the cooler periods of the year. Furthermore, survival increased with body size. However, in both cases, the directional selection estimates were nonsignificant, and the constraints of our experimental design prevented us from evaluating more complex models (i.e., nonlinear selection).}, } @article {pmid30459843, year = {2018}, author = {Qin, YJ and Krosch, MN and Schutze, MK and Zhang, Y and Wang, XX and Prabhakar, CS and Susanto, A and Hee, AKW and Ekesi, S and Badji, K and Khan, M and Wu, JJ and Wang, QL and Yan, G and Zhu, LH and Zhao, ZH and Liu, LJ and Clarke, AR and Li, ZH}, title = {Population structure of a global agricultural invasive pest, Bactrocera dorsalis (Diptera: Tephritidae).}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1990-2003}, pmid = {30459843}, issn = {1752-4571}, abstract = {Bactrocera dorsalis, the Oriental fruit fly, is one of the world's most destructive agricultural insect pests and a major impediment to international fresh commodity trade. The genetic structuring of the species across its entire geographic range has never been undertaken, because under a former taxonomy B. dorsalis was divided into four distinct taxonomic entities, each with their own, largely non-overlapping, distributions. Based on the extensive sampling of six a priori groups from 63 locations, genetic and geometric morphometric datasets were generated to detect macrogeographic population structure, and to determine prior and current invasion pathways of this species. Weak population structure and high genetic diversity were detected among Asian populations. Invasive populations in Africa and Hawaii are inferred to be the result of separate, single invasions from South Asia, while South Asia is also the likely source of other Asian populations. The current northward invasion of B. dorsalis into Central China is the result of multiple, repeated dispersal events, most likely related to fruit trade. Results are discussed in the context of global quarantine, trade, and management of this pest. The recent expansion of the fly into temperate China, with very few associated genetic changes, clearly demonstrates the threat posed by this pest to ecologically similar areas in Europe and North America.}, } @article {pmid30459842, year = {2018}, author = {Konečný, A and Popa, OP and Bartáková, V and Douda, K and Bryja, J and Smith, C and Popa, LO and Reichard, M}, title = {Modelling the invasion history of Sinanodonta woodiana in Europe: Tracking the routes of a sedentary aquatic invader with mobile parasitic larvae.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1975-1989}, pmid = {30459842}, issn = {1752-4571}, abstract = {Understanding the invasive potential of species outside their native range is one of the most pressing questions in applied evolutionary and ecological research. Admixture of genotypes of invasive species from multiple sources has been implicated in successful invasions, by generating novel genetic combinations that facilitate rapid adaptation to new environments. Alternatively, adaptive evolution on standing genetic variation, exposed by phenotypic plasticity and selected by genetic accommodation, can facilitate invasion success. We investigated the population genetic structure of an Asian freshwater mussel with a parasitic dispersal stage, Sinanodonta woodiana, which has been present in Europe since 1979 but which has expanded rapidly in the last decade. Data from a mitochondrial marker and nuclear microsatellites have suggested that all European populations of S. woodiana originate from the River Yangtze basin in China. Only a single haplotype was detected in Europe, in contrast to substantial mitochondrial diversity in native Asian populations. Analysis of microsatellite markers indicated intensive gene flow and confirmed a lower genetic diversity of European populations compared to those from the Yangtze basin, though that difference was not large. Using an Approximate Bayesian Modelling approach, we identified two areas as the probable source of the spread of S. woodiana in Europe, which matched historical records for its establishment. Their populations originated from a single colonization event. Our data do not support alternative explanations for the rapid recent spread of S. woodiana; recent arrival of a novel (cold-tolerant) genotype or continuous propagule pressure. Instead, in situ adaptation, facilitated by repeated admixture, appears to drive the ongoing expansion of S. woodiana. We discuss management consequences of our results.}, } @article {pmid30459841, year = {2018}, author = {Charbonneau, A and Tack, D and Lale, A and Goldston, J and Caple, M and Conner, E and Barazani, O and Ziffer-Berger, J and Dworkin, I and Conner, JK}, title = {Weed evolution: Genetic differentiation among wild, weedy, and crop radish.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1964-1974}, pmid = {30459841}, issn = {1752-4571}, abstract = {Approximately 200 weed species are responsible for more than 90% of crop losses and these comprise less than one percent of all named plant species, suggesting that there are only a few evolutionary routes that lead to weediness. Agricultural weeds can evolve along three main paths: they can be escaped crops, wild species, or crop-wild hybrids. We tested these three hypotheses in weedy radish, a weed of small grains and an emerging model for investigating the evolution of agricultural weeds, using 21 CAPS and SSR markers scored on 338 individuals from 34 populations representing all major species and sub-species in the radish genus Raphanus. To test for adaptation of the weeds to the agricultural environment, we estimated genetic differentiation in flowering time in a series of common garden experiments with over 2,400 individuals from 43 populations (all but one of the genotyped populations plus 10 additional populations). Our findings suggest that the agricultural weed radish R. r. raphanistrum is most genetically similar to native populations of R. r. raphanistrum and is likely not a feral crop or crop hybrid. We also show that weedy radish flowers more rapidly than any other Raphanus population or cultivar, which is consistent with rapid adaptation to the frequent and severe disturbance that characterizes agricultural fields.}, } @article {pmid30459840, year = {2018}, author = {Cai, Z and Yao, Z and Li, Y and Xi, Z and Bourtzis, K and Zhao, Z and Bai, S and Zhang, H}, title = {Intestinal probiotics restore the ecological fitness decline of Bactrocera dorsalis by irradiation.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1946-1963}, pmid = {30459840}, issn = {1752-4571}, abstract = {The sterile insect technique (SIT) as an eco-friendly and reliable strategy has been used to control populations of insect pests of agricultural, veterinary and human health importance. Successful applications of SIT rely on the high-level ecological fitness of sterile males. A suitable and stable gut microbiome can contribute to the ecological fitness of insect by influencing their physiology, biochemistry and development processes. Here, we show that a shift in the gut bacterial composition and structure by sterilizing irradiation, characterized by a decrease in the major gut microbiota community Enterobacteriaceae, an expansion of the minor members (e.g., Bacillaceae) and a higher richness and diversity, is tightly linked to radiation-induced ecological fitness (male mating competitiveness, flight capacity, survival rate and life span) decline in Bactrocera dorsalis (Hendel) sterile males. Function prediction of gut microbiota indicated that changes in microbiome taxonomy tend to drive microbiome functional shifts. A higher nutrient consumption of the flourishing minor gut microbiota may cause a decline in nutrients and energy metabolic activity of host and then result in the reduced ecological fitness of irradiated flies. Furthermore, we found that a gut bacterial strain Klebsiella oxytoca (BD177) can restore ecological fitness by improving food intake and increasing haemolymph sugar and amino acid levels of irradiated B. dorsalis flies. Our findings suggest that gut symbiont-based probiotics can be used as agents for reversing radiation-induced ecological fitness decrease.}, } @article {pmid30459839, year = {2018}, author = {Xia, H and Wang, B and Zhao, W and Pan, J and Mao, JF and Wang, XR}, title = {Combining mitochondrial and nuclear genome analyses to dissect the effects of colonization, environment, and geography on population structure in Pinus tabuliformis.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1931-1945}, pmid = {30459839}, issn = {1752-4571}, abstract = {The phylogeographic histories of plants in East Asia are complex and shaped by both past large-scale climatic oscillations and dramatic tectonic events. The impact of these historic events, as well as ecological adaptation, on the distribution of biodiversity remains to be elucidated. Pinus tabuliformis is the dominant coniferous tree in northern China, with a large distribution across wide environmental gradients. We examined genetic variation in this species using genotyping-by-sequencing and mitochondrial (mt) DNA markers. We found population structure on both nuclear and mt genomes with a geographic pattern that corresponds well with the landscape of northern China. To understand the contributions of environment, geography, and colonization history to the observed population structure, we performed ecological niche modeling and partitioned the among-population genomic variance into isolation by environment (IBE), isolation by distance (IBD), and isolation by colonization (IBC). We used mtDNA, which is transmitted by seeds in pine, to reflect colonization. We found little impact of IBE, IBD, and IBC on variation in neutral SNPs, but significant impact of IBE on a group of outlier loci. The lack of IBC illustrates that the maternal history can be quickly eroded from the nuclear genome by high rates of gene flow. Our results suggest that genomic variation in P. tabuliformis is largely affected by neutral and stochastic processes, and the signature of local adaptation is visible only at robust outlier loci. This study enriches our understanding on the complex evolutionary forces that shape the distribution of genetic variation in plant taxa in northern China, and guides breeding, conservation, and reforestation programs for P. tabuliformis.}, } @article {pmid30459838, year = {2018}, author = {Xu, T and Sun, J and Watanabe, HK and Chen, C and Nakamura, M and Ji, R and Feng, D and Lv, J and Wang, S and Bao, Z and Qian, PY and Qiu, JW}, title = {Population genetic structure of the deep-sea mussel Bathymodiolus platifrons (Bivalvia: Mytilidae) in the Northwest Pacific.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1915-1930}, pmid = {30459838}, issn = {1752-4571}, abstract = {Studying population genetics of deep-sea animals helps us understand their history of habitat colonization and population divergence. Here, we report a population genetic study of the deep-sea mussel Bathymodiolus platifrons (Bivalvia: Mytilidae) widely distributed in chemosynthesis-based ecosystems in the Northwest Pacific. Three mitochondrial genes (i.e., atp6, cox1, and nad4) and 6,398 genomewide single nucleotide polymorphisms (SNPs) were obtained from 110 individuals from four hydrothermal vents and two methane seeps. When using the three mitochondrial genes, nearly no genetic differentiation was detected for B. platifrons in the Northwest Pacific. Nevertheless, when using SNP datasets, all individuals in the South China Sea (SCS) and three individuals in Sagami Bay (SB) together formed one genetic cluster that was distinct from the remaining individuals. Such genetic divergence indicated a genetic barrier to gene flow between the SCS and the open Northwest Pacific, resulting in the co-occurrence of two cryptic semi-isolated lineages. When using 125 outlier SNPs identified focusing on individuals in the Okinawa Trough (OT) and SB, a minor genetic subdivision was detected between individuals in the southern OT (S-OT) and those in the middle OT (M-OT) and SB. This result indicated that, although under the influence of the Kuroshio Current and the North Pacific Intermediate Water, subtle geographic barriers may exist between the S-OT and the M-OT. Introgression analyses based on these outlier SNPs revealed that Hatoma Knoll in the S-OT represents a possible contact zone for individuals in the OT-SB region. Furthermore, migration dynamic analyses uncovered stronger gene flow from Dai-yon Yonaguni Knoll in the S-OT to the other local populations, compared to the reverse directions. Taken together, the present study offered novel perspectives on the genetic connectivity of B. platifrons mussels, revealing the potential interaction of ocean currents and geographic barriers with adaption and reproductive isolation in shaping their migration patterns and genetic differentiation in the Northwest Pacific.}, } @article {pmid30459837, year = {2018}, author = {Zhang, GK and Chain, FJJ and Abbott, CL and Cristescu, ME}, title = {Metabarcoding using multiplexed markers increases species detection in complex zooplankton communities.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1901-1914}, pmid = {30459837}, issn = {1752-4571}, abstract = {Metabarcoding combines DNA barcoding with high-throughput sequencing, often using one genetic marker to understand complex and taxonomically diverse samples. However, species-level identification depends heavily on the choice of marker and the selected primer pair, often with a trade-off between successful species amplification and taxonomic resolution. We present a versatile metabarcoding protocol for biomonitoring that involves the use of two barcode markers (COI and 18S) and four primer pairs in a single high-throughput sequencing run, via sample multiplexing. We validate the protocol using a series of 24 mock zooplanktonic communities incorporating various levels of genetic variation. With the use of a single marker and single primer pair, the highest species recovery was 77%. With all three COI fragments, we detected 62%-83% of species across the mock communities, while the use of the 18S fragment alone resulted in the detection of 73%-75% of species. The species detection level was significantly improved to 89%-93% when both markers were used. Furthermore, multiplexing did not have a negative impact on the proportion of reads assigned to each species and the total number of species detected was similar to when markers were sequenced alone. Overall, our metabarcoding approach utilizing two barcode markers and multiple primer pairs per barcode improved species detection rates over a single marker/primer pair by 14% to 35%, making it an attractive and relatively cost-effective method for biomonitoring natural zooplankton communities. We strongly recommend combining evolutionary independent markers and, when necessary, multiple primer pairs per marker to increase species detection (i.e., reduce false negatives) in metabarcoding studies.}, } @article {pmid30459836, year = {2018}, author = {Kodama, M and Naish, KA and Devlin, RH}, title = {Influence of a growth hormone transgene on the genetic architecture of growth-related traits: A comparative analysis between transgenic and wild-type coho salmon.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1886-1900}, pmid = {30459836}, issn = {1752-4571}, abstract = {Genetic engineering has been increasingly applied to many commercially important plant and animal species, generating phenotypic changes that are not observed in natural populations and creating genetic interactions that have not experienced natural selection. The degree to and way in which such human-induced genetic variation interacts with the rest of the genome is currently largely unknown. Integrating such information into ecological and risk assessment frameworks is crucial to understand the potential effects of genetically modified organisms in natural environments. Here, we performed QTL mapping to investigate the genetic architecture of growth-related traits in nontransgenic (NT) and growth hormone transgenic (T) coho salmon with large changes in growth and related physiology, with the aim of identifying how an inserted transgene might influence the opportunity for selection. These fish shared the same parental genetic background, thus allowing us to determine whether the same or different loci influence these traits within the two groups. The use of over 1,700 loci, derived from restriction site-associated DNA sequencing, revealed that different genomic regions were linked with growth over time between the two groups. Additionally, the effect sizes of detected QTL appear to have been influenced by the transgene. Direct comparison of QTL between the T and NT fish during two size-matched periods identified little overlap in their location. Taken together, the results showed that the transgene altered the genetic basis of growth-related traits in this species. The study has important implications for effective conservation and management of wild populations experiencing introduction of transgenes. Evolutionary changes and their ecological consequences may occur at different rates and in different directions in NT versus T individuals in response to selection. Thus, assessments of phenotypic change, and hence ecological risk, should be determined periodically to evaluate whether initial estimates made with founder strains remain valid.}, } @article {pmid30459835, year = {2018}, author = {Heckwolf, MJ and Meyer, BS and Döring, T and Eizaguirre, C and Reusch, TBH}, title = {Transgenerational plasticity and selection shape the adaptive potential of sticklebacks to salinity change.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1873-1885}, pmid = {30459835}, issn = {1752-4571}, abstract = {In marine climate change research, salinity shifts have been widely overlooked. While widespread desalination effects are expected in higher latitudes, salinity is predicted to increase closer to the equator. We took advantage of the steep salinity gradient of the Baltic Sea as a space-for-time design to address effects of salinity change on populations. Additionally, genetic diversity, a prerequisite for adaptive responses, is reduced in Baltic compared to Atlantic populations. On the one hand, adaptive transgenerational plasticity (TGP) might buffer the effects of environmental change, which may be of particular importance under reduced genetic variation. On the other hand, physiological trade-offs due to environmental stress may hamper parental provisioning to offspring thereby intensifying the impact of climate change across generations (nonadaptive TGP). Here, we studied both hypothesis of adaptive and nonadaptive TGP in the three-spined stickleback (Gasterosteus aculeatus) fish model along the strong salinity gradient of the Baltic Sea in a space-for-time experiment. Each population tolerated desalination well, which was not altered by parental exposure to low salinity. Despite a common marine ancestor, populations locally adapted to low salinity lost their ability to cope with fully marine conditions, resulting in lower survival and reduced relative fitness. Negative transgenerational effects were evident in early life stages, but disappeared after selection via mortality occurred during the first 12-30 days posthatch. Modeling various strengths of selection, we showed that nonadaptive transgenerational plasticity accelerated evolution by increasing directional selection within the offspring generation. Qualitatively, when genetic diversity is large, we predict that such effects will facilitate rapid adaptation and population persistence, while below a certain threshold populations suffer a higher risk of local extinction. Overall, our results suggest that transgenerational plasticity and selection are not independent of each other and thereby highlight a current gap in TGP studies.}, } @article {pmid30459834, year = {2018}, author = {Ma, T and Hu, Y and Russo, IM and Nie, Y and Yang, T and Xiong, L and Ma, S and Meng, T and Han, H and Zhang, X and Bruford, MW and Wei, F}, title = {Walking in a heterogeneous landscape: Dispersal, gene flow and conservation implications for the giant panda in the Qinling Mountains.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1859-1872}, pmid = {30459834}, issn = {1752-4571}, abstract = {Understanding the interaction between life history, demography and population genetics in threatened species is critical for the conservations of viable populations. In the context of habitat loss and fragmentation, identifying the factors that underpin the structuring of genetic variation within populations can allow conservationists to evaluate habitat quality and connectivity and help to design dispersal corridors effectively. In this study, we carried out a detailed, fine-scale landscape genetic investigation of a giant panda population from the Qinling Mountains for the first time. With a large microsatellite data set and complementary analysis methods, we examined the role of isolation-by-barriers (IBB), isolation-by-distance (IBD) and isolation-by-resistance (IBR) in shaping the pattern of genetic variation in this giant panda population. We found that the Qinling population comprises one continuous genetic cluster, and among the landscape hypotheses tested, gene flow was found to be correlated with resistance gradients for two topographic factors, slope aspect and topographic complexity, rather than geographical distance or barriers. Gene flow was inferred to be facilitated by easterly slope aspect and to be constrained by topographically complex landscapes. These factors are related to benign microclimatic conditions for both the pandas and the food resources they rely on and more accessible topographic conditions for movement, respectively. We identified optimal corridors based on these results, aiming to promote gene flow between human-induced habitat fragments. These findings provide insight into the permeability and affinities of giant panda habitats and offer important reference for the conservation of the giant panda and its habitat.}, } @article {pmid30459833, year = {2018}, author = {Martins, K and Gugger, PF and Llanderal-Mendoza, J and González-Rodríguez, A and Fitz-Gibbon, ST and Zhao, JL and Rodríguez-Correa, H and Oyama, K and Sork, VL}, title = {Landscape genomics provides evidence of climate-associated genetic variation in Mexican populations of Quercus rugosa.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1842-1858}, pmid = {30459833}, issn = {1752-4571}, abstract = {Local adaptation is a critical evolutionary process that allows plants to grow better in their local compared to non-native habitat and results in species-wide geographic patterns of adaptive genetic variation. For forest tree species with a long generation time, this spatial genetic heterogeneity can shape the ability of trees to respond to rapid climate change. Here, we identify genomic variation that may confer local environmental adaptations and then predict the extent of adaptive mismatch under future climate as a tool for forest restoration or management of the widely distributed high-elevation oak species Quercus rugosa in Mexico. Using genotyping by sequencing, we identified 5,354 single nucleotide polymorphisms (SNPs) genotyped from 103 individuals across 17 sites in the Trans-Mexican Volcanic Belt, and, after controlling for neutral genetic structure, we detected 74 FST outlier SNPs and 97 SNPs associated with climate variation. Then, we deployed a nonlinear multivariate model, Gradient Forests, to map turnover in allele frequencies along environmental gradients and predict areas most sensitive to climate change. We found that spatial patterns of genetic variation were most strongly associated with precipitation seasonality and geographic distance. We identified regions of contemporary genetic and climatic similarities and predicted regions where future populations of Q. rugosa might be at risk due to high expected rate of climate change. Our findings provide preliminary details for future management strategies of Q. rugosa in Mexico and also illustrate how a landscape genomic approach can provide a useful tool for conservation and resource management strategies.}, } @article {pmid30459832, year = {2018}, author = {Okamoto, KW and Post, DM and Vasseur, DA and Turner, PE}, title = {Managing the emergence of pathogen resistance via spatially targeted antimicrobial use.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1822-1841}, pmid = {30459832}, issn = {1752-4571}, abstract = {From agriculture to public health to civil engineering, managing antimicrobial resistance presents a considerable challenge. The dynamics underlying resistance evolution reflect inherently spatial processes. Resistant pathogen strains increase in frequency when a strain that emerges in one locale can spread and replace pathogen subpopulations formerly sensitive to the antimicrobial agent. Moreover, the strength of selection for antimicrobial resistance is in part governed by the extent of antimicrobial use. Thus, altering how antimicrobials are used across a landscape can potentially shift the spatial context governing the dynamics of antimicrobial resistance and provide a potent management tool. Here, we model how the efficacy of adjusting antimicrobial use over space to manage antimicrobial resistance is mediated by competition among pathogen strains and the topology of pathogen metapopulations. For several pathogen migration scenarios, we derive critical thresholds for the spatial extent of antimicrobial use below which resistance cannot emerge, and relate these thresholds to (a) the ability to eradicate antimicrobial-sensitive pathogens locally and (b) the strength of the trade-off between resistance ability and competitive performance where antimicrobial use is absent. We find that in metapopulations where patches differ in connectedness, constraining antimicrobial use across space to mitigate resistance evolution only works if the migration of the resistant pathogen is modest; yet, this situation is reversed if the resistant strain has a high colonization rate, with variably connected metapopulations exhibiting less sensitivity to reducing antimicrobial use across space. Furthermore, when pathogens are alternately exposed to sites with and without the antimicrobial, bottlenecking resistant strains through sites without an antimicrobial is only likely to be effective under a strong competition-resistance trade-off. We therefore identify life-history constraints that are likely to suggest which pathogens can most effectively be controlled by a spatially targeted antimicrobial regime. We discuss implications of our results for managing and thinking about antimicrobial resistance evolution in spatially heterogeneous contexts.}, } @article {pmid30459831, year = {2018}, author = {Jensen, EL and Edwards, DL and Garrick, RC and Miller, JM and Gibbs, JP and Cayot, LJ and Tapia, W and Caccone, A and Russello, MA}, title = {Population genomics through time provides insights into the consequences of decline and rapid demographic recovery through head-starting in a Galapagos giant tortoise.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1811-1821}, pmid = {30459831}, issn = {1752-4571}, abstract = {Population genetic theory related to the consequences of rapid population decline is well-developed, but there are very few empirical studies where sampling was conducted before and after a known bottleneck event. Such knowledge is of particular importance for species restoration, given links between genetic diversity and the probability of long-term persistence. To directly evaluate the relationship between current genetic diversity and past demographic events, we collected genome-wide single nucleotide polymorphism data from prebottleneck historical (c.1906) and postbottleneck contemporary (c.2014) samples of Pinzón giant tortoises (Chelonoidis duncanensis; n = 25 and 149 individuals, respectively) endemic to a single island in the Galapagos. Pinzón giant tortoises had a historically large population size that was reduced to just 150-200 individuals in the mid 20th century. Since then, Pinzón's tortoise population has recovered through an ex situ head-start programme in which eggs or pre-emergent individuals were collected from natural nests on the island, reared ex situ in captivity until they were 4-5 years old and subsequently repatriated. We found that the extent and distribution of genetic variation in the historical and contemporary samples were very similar, with the latter group not exhibiting the characteristic genetic patterns of recent population decline. No population structure was detected either spatially or temporally. We estimated an effective population size (Ne) of 58 (95% CI = 50-69) for the postbottleneck population; no prebottleneck Ne point estimate was attainable (95% CI = 39-infinity) likely due to the sample size being lower than the true Ne. Overall, the historical sample provided a valuable benchmark for evaluating the head-start captive breeding programme, revealing high retention of genetic variation and no skew in representation despite the documented bottleneck event. Moreover, this work demonstrates the effectiveness of head-starting in rescuing the Pinzón giant tortoise from almost certain extinction.}, } @article {pmid30459830, year = {2018}, author = {Rimbaud, L and Papaïx, J and Barrett, LG and Burdon, JJ and Thrall, PH}, title = {Mosaics, mixtures, rotations or pyramiding: What is the optimal strategy to deploy major gene resistance?.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1791-1810}, pmid = {30459830}, issn = {1752-4571}, abstract = {Once deployed uniformly in the field, genetically controlled plant resistance is often quickly overcome by pathogens, resulting in dramatic losses. Several strategies have been proposed to constrain the evolutionary potential of pathogens and thus increase resistance durability. These strategies can be classified into four categories, depending on whether resistance sources are varied across time (rotations) or combined in space in the same cultivar (pyramiding), in different cultivars within a field (cultivar mixtures) or among fields (mosaics). Despite their potential to differentially affect both pathogen epidemiology and evolution, to date the four categories of deployment strategies have never been directly compared together within a single theoretical or experimental framework, with regard to efficiency (ability to reduce disease impact) and durability (ability to limit pathogen evolution and delay resistance breakdown). Here, we used a spatially explicit stochastic demogenetic model, implemented in the R package landsepi, to assess the epidemiological and evolutionary outcomes of these deployment strategies when two major resistance genes are present. We varied parameters related to pathogen evolutionary potential (mutation probability and associated fitness costs) and landscape organization (mostly the relative proportion of each cultivar in the landscape and levels of spatial or temporal aggregation). Our results, broadly focused on qualitative resistance to rust fungi of cereal crops, show that evolutionary and epidemiological control are not necessarily correlated and that no deployment strategy is universally optimal. Pyramiding two major genes offered the highest durability, but at high mutation probabilities, mosaics, mixtures and rotations can perform better in delaying the establishment of a universally infective superpathogen. All strategies offered the same short-term epidemiological control, whereas rotations provided the best long-term option, after all sources of resistance had broken down. This study also highlights the significant impact of landscape organization and pathogen evolutionary ability in considering the optimal design of a deployment strategy.}, } @article {pmid30459829, year = {2018}, author = {Gagne, RB and Tinker, MT and Gustafson, KD and Ralls, K and Larson, S and Tarjan, LM and Miller, MA and Ernest, HB}, title = {Measures of effective population size in sea otters reveal special considerations for wide-ranging species.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1779-1790}, pmid = {30459829}, issn = {1752-4571}, abstract = {Conservation genetic techniques and considerations of the evolutionary potential of a species are increasingly being applied to species conservation. For example, effective population size (Ne) estimates are useful for determining the conservation status of species, yet accurate estimates of current Ne remain difficult to obtain. The effective population size can contribute to setting federal delisting criteria, as was done for the southern sea otter (Enhydra lutris nereis). After being hunted to near extinction during the North Pacific fur trade, the southern sea otter has recovered over part of its former range, but remains at relatively low numbers, making it desirable to obtain accurate and consistent estimates of Ne. Although theoretical papers have compared the validity of several methods, comparisons of estimators using empirical data in applied conservation settings are limited. We combined thirteen years of demographic and genetic data from 1,006 sea otters to assess multiple Ne estimators, as well as temporal trends in genetic diversity and population genetic structure. Genetic diversity was low and did not increase over time. There was no evidence for distinct genetic units, but some evidence for genetic isolation by distance. In particular, estimates of Ne based on demographic data were much larger than genetic estimates when computed for the entire range of the population, but were similar at smaller spatial scales. The discrepancy between estimates at large spatial scales could be driven by cryptic population structure and/or individual differences in reproductive success. We recommend the development of new delisting criteria for the southern sea otter. We advise the use of multiple estimates of Ne for other wide-ranging species, species with overlapping generations, or with sex-biased dispersal, as well as the development of improved metrics of genetic assessments of populations.}, } @article {pmid30459828, year = {2018}, author = {Kozakiewicz, CP and Burridge, CP and Funk, WC and VandeWoude, S and Craft, ME and Crooks, KR and Ernest, HB and Fountain-Jones, NM and Carver, S}, title = {Pathogens in space: Advancing understanding of pathogen dynamics and disease ecology through landscape genetics.}, journal = {Evolutionary applications}, volume = {11}, number = {10}, pages = {1763-1778}, pmid = {30459828}, issn = {1752-4571}, abstract = {Landscape genetics has provided many insights into how heterogeneous landscape features drive processes influencing spatial genetic variation in free-living organisms. This rapidly developing field has focused heavily on vertebrates, and expansion of this scope to the study of infectious diseases holds great potential for landscape geneticists and disease ecologists alike. The potential application of landscape genetics to infectious agents has garnered attention at formative stages in the development of landscape genetics, but systematic examination is lacking. We comprehensively review how landscape genetics is being used to better understand pathogen dynamics. We characterize the field and evaluate the types of questions addressed, approaches used and systems studied. We also review the now established landscape genetic methods and their realized and potential applications to disease ecology. Lastly, we identify emerging frontiers in the landscape genetic study of infectious agents, including recent phylogeographic approaches and frameworks for studying complex multihost and host-vector systems. Our review emphasizes the expanding utility of landscape genetic methods available for elucidating key pathogen dynamics (particularly transmission and spread) and also how landscape genetic studies of pathogens can provide insight into host population dynamics. Through this review, we convey how increasing awareness of the complementarity of landscape genetics and disease ecology among practitioners of each field promises to drive important cross-disciplinary advances.}, } @article {pmid30459480, year = {2018}, author = {Dańko, MJ and Burger, O and Argasiński, K and Kozłowski, J}, title = {Extrinsic Mortality Can Shape Life-History Traits, Including Senescence.}, journal = {Evolutionary biology}, volume = {45}, number = {4}, pages = {395-404}, pmid = {30459480}, issn = {0071-3260}, abstract = {The Williams' hypothesis is one of the most widely known ideas in life history evolution. It states that higher adult mortality should lead to faster and/or earlier senescence. Theoretically derived gradients, however, do not support this prediction. Increased awareness of this fact has caused a crisis of misinformation among theorists and empirical ecologists. We resolve this crisis by outlining key issues in the measurement of fitness, assumptions of density dependence, and their effect on extrinsic mortality. The classic gradients apply only to a narrow range of ecological contexts where density-dependence is either absent or present but with unrealistic stipulations. Re-deriving the classic gradients, using a more appropriate measure of fitness and incorporating density, shows that broad ecological contexts exist where Williams' hypothesis is supported.}, } @article {pmid30459479, year = {2018}, author = {Larsson, M and Abbott, BW}, title = {Is the Capacity for Vocal Learning in Vertebrates Rooted in Fish Schooling Behavior?.}, journal = {Evolutionary biology}, volume = {45}, number = {4}, pages = {359-373}, pmid = {30459479}, issn = {0071-3260}, abstract = {The capacity to learn and reproduce vocal sounds has evolved in phylogenetically distant tetrapod lineages. Vocal learners in all these lineages express similar neural circuitry and genetic factors when perceiving, processing, and reproducing vocalization, suggesting that brain pathways for vocal learning evolved within strong constraints from a common ancestor, potentially fish. We hypothesize that the auditory-motor circuits and genes involved in entrainment have their origins in fish schooling behavior and respiratory-motor coupling. In this acoustic advantages hypothesis, aural costs and benefits played a key role in shaping a wide variety of traits, which could readily be exapted for entrainment and vocal learning, including social grouping, group movement, and respiratory-motor coupling. Specifically, incidental sounds of locomotion and respiration (ISLR) may have reinforced synchronization by communicating important spatial and temporal information between school-members and extending windows of silence to improve situational awareness. This process would be mutually reinforcing. Neurons in the telencephalon, which were initially involved in linking ISLR with forelimbs, could have switched functions to serve vocal machinery (e.g. mouth, beak, tongue, larynx, syrinx). While previous vocal learning hypotheses invoke transmission of neurons from visual tasks (gestures) to the auditory channel, this hypothesis involves the auditory channel from the onset. Acoustic benefits of locomotor-respiratory coordination in fish may have selected for genetic factors and brain circuitry capable of synchronizing respiratory and limb movements, predisposing tetrapod lines to synchronized movement, vocalization, and vocal learning. We discuss how the capacity to entrain is manifest in fish, amphibians, birds, and mammals, and propose predictions to test our acoustic advantages hypothesis.}, } @article {pmid30459470, year = {2018}, author = {Naganuma, M and Sekine, SI and Chong, YE and Guo, M and Yang, XL and Gamper, H and Hou, YM and Schimmel, P and Yokoyama, S}, title = {Author Correction: The selective tRNA aminoacylation mechanism based on a single G•U pair.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {E37}, doi = {10.1038/s41586-018-0760-4}, pmid = {30459470}, issn = {1476-4687}, abstract = {In Fig. 1b of this Article, a U was inadvertently inserted after G15 in the D loop. The original Article has not been corrected.}, } @article {pmid30459387, year = {2018}, author = {}, title = {Brexit end game leaves much to play for.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {443-444}, doi = {10.1038/d41586-018-07478-8}, pmid = {30459387}, issn = {1476-4687}, } @article {pmid30459386, year = {2018}, author = {Phillips, N}, title = {Antarctic scientists begin hunt for sky's 'detergent'.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {455-456}, doi = {10.1038/d41586-018-07422-w}, pmid = {30459386}, issn = {1476-4687}, } @article {pmid30459385, year = {2018}, author = {Kerr, W}, title = {America, don't throw global talent away.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {445}, doi = {10.1038/d41586-018-07446-2}, pmid = {30459385}, issn = {1476-4687}, } @article {pmid30459384, year = {2018}, author = {Witze, A}, title = {Why extreme rains are gaining strength as the climate warms.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {458-460}, doi = {10.1038/d41586-018-07447-1}, pmid = {30459384}, issn = {1476-4687}, } @article {pmid30459383, year = {2018}, author = {Powell, K}, title = {Why graduate students should get involved in advocacy.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {589-590}, doi = {10.1038/d41586-018-07442-6}, pmid = {30459383}, issn = {1476-4687}, } @article {pmid30459382, year = {2018}, author = {Reardon, S}, title = {Lab-grown 'mini brains' produce electrical patterns that resemble those of premature babies.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {453}, doi = {10.1038/d41586-018-07402-0}, pmid = {30459382}, issn = {1476-4687}, } @article {pmid30459381, year = {2018}, author = {}, title = {Molecular net fishes sugar from blood.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {447}, doi = {10.1038/d41586-018-07406-w}, pmid = {30459381}, issn = {1476-4687}, } @article {pmid30459380, year = {2018}, author = {}, title = {Photobombing stars lead to cosmic false identity.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {447}, doi = {10.1038/d41586-018-07413-x}, pmid = {30459380}, issn = {1476-4687}, } @article {pmid30459379, year = {2018}, author = {Hall, S}, title = {World's first automated volcano forecast predicts Mount Etna's eruptions.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {456-457}, doi = {10.1038/d41586-018-07420-y}, pmid = {30459379}, issn = {1476-4687}, } @article {pmid30459378, year = {2018}, author = {Callaway, E}, title = {Ban on 'gene drives' is back on the UN's agenda - worrying scientists.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {454-455}, doi = {10.1038/d41586-018-07436-4}, pmid = {30459378}, issn = {1476-4687}, } @article {pmid30459377, year = {2018}, author = {Gibney, E and Else, H}, title = {Brexit: what the draft deal means for science.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {452-453}, doi = {10.1038/d41586-018-07423-9}, pmid = {30459377}, issn = {1476-4687}, } @article {pmid30459376, year = {2018}, author = {}, title = {Crater gouged by huge space rock found under Greenland ice.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {446-447}, doi = {10.1038/d41586-018-07421-x}, pmid = {30459376}, issn = {1476-4687}, } @article {pmid30459375, year = {2018}, author = {}, title = {Massive trial shows limited value for popular supplements.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {447}, doi = {10.1038/d41586-018-07391-0}, pmid = {30459375}, issn = {1476-4687}, } @article {pmid30459374, year = {2018}, author = {}, title = {A dragon that prefers a quiet life at home.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {446}, doi = {10.1038/d41586-018-07400-2}, pmid = {30459374}, issn = {1476-4687}, } @article {pmid30459373, year = {2018}, author = {}, title = {Plump mice help to unravel the tangled ties between obesity and cancer.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {446}, doi = {10.1038/d41586-018-07390-1}, pmid = {30459373}, issn = {1476-4687}, } @article {pmid30459372, year = {2018}, author = {}, title = {Ancient Celts embalmed enemy heads as trophies.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {447}, doi = {10.1038/d41586-018-07375-0}, pmid = {30459372}, issn = {1476-4687}, } @article {pmid30459371, year = {2018}, author = {Celniker, SE}, title = {Improved mosquito genome points to population-control strategies.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {482-483}, doi = {10.1038/d41586-018-07266-4}, pmid = {30459371}, issn = {1476-4687}, mesh = {Aedes/*genetics ; Animals ; *Arboviruses ; Genome ; Genomics ; Mosquito Vectors ; }, } @article {pmid30459370, year = {2018}, author = {Chiao, M}, title = {Rock legend retells the race to the Moon - in 3D.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {469-470}, doi = {10.1038/d41586-018-07342-9}, pmid = {30459370}, issn = {1476-4687}, } @article {pmid30459369, year = {2018}, author = {Dutcher, JR}, title = {Nanofibres induce remodelling of cell membranes.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {481-482}, doi = {10.1038/d41586-018-07261-9}, pmid = {30459369}, issn = {1476-4687}, mesh = {Cell Adhesion ; *Cell Membrane ; *Nanofibers ; Physical Phenomena ; Wettability ; }, } @article {pmid30459368, year = {2018}, author = {Schlacher, K}, title = {A new road to cancer-drug resistance.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {478-480}, doi = {10.1038/d41586-018-07188-1}, pmid = {30459368}, issn = {1476-4687}, mesh = {DNA ; *Drug Resistance, Neoplasm ; Humans ; *Neoplasms ; }, } @article {pmid30459367, year = {2018}, author = {Becker, LA and Gitler, AD}, title = {A neurodegenerative-disease protein forms beneficial aggregates in healthy muscle.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {477-478}, doi = {10.1038/d41586-018-07141-2}, pmid = {30459367}, issn = {1476-4687}, } @article {pmid30459277, year = {2018}, author = {Zhang, Z and Liu, F and Chen, J}, title = {Molecular structure of the ATP-bound, phosphorylated human CFTR.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12757-12762}, doi = {10.1073/pnas.1815287115}, pmid = {30459277}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/*chemistry/*metabolism ; Animals ; Cell Line ; Cryoelectron Microscopy/methods ; Cyclic AMP-Dependent Protein Kinases/chemistry/metabolism ; Cystic Fibrosis/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/*chemistry/*metabolism ; HEK293 Cells ; Humans ; Ion Channel Gating/physiology ; Ion Transport/physiology ; Molecular Structure ; Mutation/genetics ; Phosphorylation ; Zebrafish ; }, abstract = {The cystic fibrosis transmembrane conductance regulator (CFTR) is an anion channel important in maintaining proper functions of the lung, pancreas, and intestine. The activity of CFTR is regulated by ATP and protein kinase A-dependent phosphorylation. To understand the conformational changes elicited by phosphorylation and ATP binding, we present here the structure of phosphorylated, ATP-bound human CFTR, determined by cryoelectron microscopy to 3.2-Å resolution. This structure reveals the position of the R domain after phosphorylation. By comparing the structures of human CFTR and zebrafish CFTR determined under the same condition, we identified common features essential to channel gating. The differences in their structures indicate plasticity permitted in evolution to achieve the same function. Finally, the structure of CFTR provides a better understanding of why the G178R, R352Q, L927P, and G970R/D mutations would impede conformational changes of CFTR and lead to cystic fibrosis.}, } @article {pmid30459276, year = {2018}, author = {Trudeau, DL and Edlich-Muth, C and Zarzycki, J and Scheffen, M and Goldsmith, M and Khersonsky, O and Avizemer, Z and Fleishman, SJ and Cotton, CAR and Erb, TJ and Tawfik, DS and Bar-Even, A}, title = {Design and in vitro realization of carbon-conserving photorespiration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11455-E11464}, doi = {10.1073/pnas.1812605115}, pmid = {30459276}, issn = {1091-6490}, abstract = {Photorespiration recycles ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco) oxygenation product, 2-phosphoglycolate, back into the Calvin Cycle. Natural photorespiration, however, limits agricultural productivity by dissipating energy and releasing CO2 Several photorespiration bypasses have been previously suggested but were limited to existing enzymes and pathways that release CO2 Here, we harness the power of enzyme and metabolic engineering to establish synthetic routes that bypass photorespiration without CO2 release. By defining specific reaction rules, we systematically identified promising routes that assimilate 2-phosphoglycolate into the Calvin Cycle without carbon loss. We further developed a kinetic-stoichiometric model that indicates that the identified synthetic shunts could potentially enhance carbon fixation rate across the physiological range of irradiation and CO2, even if most of their enzymes operate at a tenth of Rubisco's maximal carboxylation activity. Glycolate reduction to glycolaldehyde is essential for several of the synthetic shunts but is not known to occur naturally. We, therefore, used computational design and directed evolution to establish this activity in two sequential reactions. An acetyl-CoA synthetase was engineered for higher stability and glycolyl-CoA synthesis. A propionyl-CoA reductase was engineered for higher selectivity for glycolyl-CoA and for use of NADPH over NAD+, thereby favoring reduction over oxidation. The engineered glycolate reduction module was then combined with downstream condensation and assimilation of glycolaldehyde to ribulose 1,5-bisphosphate, thus providing proof of principle for a carbon-conserving photorespiration pathway.}, } @article {pmid30459275, year = {2018}, author = {Ray, P and Chin, AS and Worley, KE and Fan, J and Kaur, G and Wu, M and Wan, LQ}, title = {Intrinsic cellular chirality regulates left-right symmetry breaking during cardiac looping.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11568-E11577}, doi = {10.1073/pnas.1808052115}, pmid = {30459275}, issn = {1091-6490}, support = {DP2 HD083961/HD/NICHD NIH HHS/United States ; R01 HL121700/HL/NHLBI NIH HHS/United States ; }, abstract = {The vertebrate body plan is overall symmetrical but left-right (LR) asymmetric in the shape and positioning of internal organs. Although several theories have been proposed, the biophysical mechanisms underlying LR asymmetry are still unclear, especially the role of cell chirality, the LR asymmetry at the cellular level, on organ asymmetry. Here with developing chicken embryos, we examine whether intrinsic cell chirality or handedness regulates cardiac C looping. Using a recently established biomaterial-based 3D culture platform, we demonstrate that chick cardiac cells before and during C looping are intrinsically chiral and exhibit dominant clockwise rotation in vitro. We further show that cells in the developing myocardium are chiral as evident by a rightward bias of cell alignment and a rightward polarization of the Golgi complex, correlating with the direction of cardiac tube rotation. In addition, there is an LR polarized distribution of N-cadherin and myosin II in the myocardium before the onset of cardiac looping. More interestingly, the reversal of cell chirality via activation of the protein kinase C signaling pathway reverses the directionality of cardiac looping, accompanied by a reversal in cellular biases on the cardiac tube. Our results suggest that myocardial cell chirality regulates cellular LR symmetry breaking in the heart tube and the resultant directionality of cardiac looping. Our study provides evidence of an intrinsic cellular chiral bias leading to LR symmetry breaking during directional tissue rotation in vertebrate development.}, } @article {pmid30459274, year = {2018}, author = {Ho, PH and Farmer, DB and Tulevski, GS and Han, SJ and Bishop, DM and Gignac, LM and Bucchignano, J and Avouris, P and Falk, AL}, title = {Intrinsically ultrastrong plasmon-exciton interactions in crystallized films of carbon nanotubes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12662-12667}, doi = {10.1073/pnas.1816251115}, pmid = {30459274}, issn = {1091-6490}, abstract = {In cavity quantum electrodynamics, optical emitters that are strongly coupled to cavities give rise to polaritons with characteristics of both the emitters and the cavity excitations. We show that carbon nanotubes can be crystallized into chip-scale, two-dimensionally ordered films and that this material enables intrinsically ultrastrong emitter-cavity interactions: Rather than interacting with external cavities, nanotube excitons couple to the near-infrared plasmon resonances of the nanotubes themselves. Our polycrystalline nanotube films have a hexagonal crystal structure, ∼25-nm domains, and a 1.74-nm lattice constant. With this extremely high nanotube density and nearly ideal plasmon-exciton spatial overlap, plasmon-exciton coupling strengths reach 0.5 eV, which is 75% of the bare exciton energy and a near record for room-temperature ultrastrong coupling. Crystallized nanotube films represent a milestone in nanomaterials assembly and provide a compelling foundation for high-ampacity conductors, low-power optical switches, and tunable optical antennas.}, } @article {pmid30459273, year = {2018}, author = {Fu, T and Liu, J and Wang, Y and Xie, X and Hu, S and Pan, L}, title = {Mechanistic insights into the interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11651-E11660}, doi = {10.1073/pnas.1811421115}, pmid = {30459273}, issn = {1091-6490}, abstract = {NDP52 and TAX1BP1, two SKIP carboxyl homology (SKICH) domain-containing autophagy receptors, play crucial roles in selective autophagy. The autophagic functions of NDP52 and TAX1BP1 are regulated by TANK-binding kinase 1 (TBK1), which may associate with them through the adaptor NAP1. However, the molecular mechanism governing the interactions of NAP1 with NDP52 and TAX1BP1, as well as the effects induced by TBK1-mediated phosphorylation of NDP52 and TAX1BP1, remains elusive. Here, we report the atomic structures of the SKICH regions of NDP52 and TAX1BP1 in complex with NAP1, which not only uncover the mechanistic bases underpinning the specific interactions of NAP1 with the SKICH domains of NDP52 and TAX1BP1 but also reveal the binding mode of a SKICH domain. Moreover, we uncovered that the SKICH domains of NDP52 and TAX1BP1 share a general binding mode to interact with NAP1. Finally, we also evaluated the currently known TBK1-mediated phosphorylation sites in the SKICH domains of NDP52 and TAX1BP1 on the basis of their interactions with NAP1. In all, our findings provide mechanistic insights into the interactions of NAP1 with NDP52 and TAX1BP1, and are valuable for further understanding the functions of these proteins in selective autophagy.}, } @article {pmid30459272, year = {2018}, author = {Pogorelyy, MV and Minervina, AA and Touzel, MP and Sycheva, AL and Komech, EA and Kovalenko, EI and Karganova, GG and Egorov, ES and Komkov, AY and Chudakov, DM and Mamedov, IZ and Mora, T and Walczak, AM and Lebedev, YB}, title = {Precise tracking of vaccine-responding T cell clones reveals convergent and personalized response in identical twins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12704-12709}, doi = {10.1073/pnas.1809642115}, pmid = {30459272}, issn = {1091-6490}, mesh = {Antigens, Viral/immunology ; Humans ; Immunization/methods ; Receptors, Antigen, T-Cell/immunology ; T-Lymphocytes/*immunology ; Tissue Donors ; Twins, Monozygotic ; Vaccination/methods ; Yellow Fever Vaccine/*immunology ; }, abstract = {T cell receptor (TCR) repertoire data contain information about infections that could be used in disease diagnostics and vaccine development, but extracting that information remains a major challenge. Here we developed a statistical framework to detect TCR clone proliferation and contraction from longitudinal repertoire data. We applied this framework to data from three pairs of identical twins immunized with the yellow fever vaccine. We identified 600 to 1,700 responding TCRs in each donor and validated them using three independent assays. While the responding TCRs were mostly private, albeit with higher overlap between twins, they could be well-predicted using a classifier based on sequence similarity. Our method can also be applied to samples obtained postinfection, making it suitable for systematic discovery of new infection-specific TCRs in the clinic.}, } @article {pmid30459271, year = {2018}, author = {Dietz, T and Whitley, CT}, title = {Environmentalism, norms, and identity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12334-12336}, doi = {10.1073/pnas.1817487115}, pmid = {30459271}, issn = {1091-6490}, mesh = {*Minority Groups ; Poverty ; *Social Identification ; United States ; }, } @article {pmid30459270, year = {2018}, author = {Stella, M and Ferrara, E and De Domenico, M}, title = {Bots increase exposure to negative and inflammatory content in online social systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12435-12440}, doi = {10.1073/pnas.1803470115}, pmid = {30459270}, issn = {1091-6490}, abstract = {Societies are complex systems, which tend to polarize into subgroups of individuals with dramatically opposite perspectives. This phenomenon is reflected-and often amplified-in online social networks, where, however, humans are no longer the only players and coexist alongside with social bots-that is, software-controlled accounts. Analyzing large-scale social data collected during the Catalan referendum for independence on October 1, 2017, consisting of nearly 4 millions Twitter posts generated by almost 1 million users, we identify the two polarized groups of Independentists and Constitutionalists and quantify the structural and emotional roles played by social bots. We show that bots act from peripheral areas of the social system to target influential humans of both groups, bombarding Independentists with violent contents, increasing their exposure to negative and inflammatory narratives, and exacerbating social conflict online. Our findings stress the importance of developing countermeasures to unmask these forms of automated social manipulation.}, } @article {pmid30459269, year = {2018}, author = {Dickey, BF}, title = {What it takes for a cough to expel mucus from the airway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12340-12342}, doi = {10.1073/pnas.1817484115}, pmid = {30459269}, issn = {1091-6490}, support = {R01 HL129795/HL/NHLBI NIH HHS/United States ; R21 AI137319/AI/NIAID NIH HHS/United States ; }, } @article {pmid30459267, year = {2018}, author = {Beans, C}, title = {News Feature: Exposing the exposome to elucidate disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11859-11862}, pmid = {30459267}, issn = {1091-6490}, mesh = {Air Pollutants/*analysis ; Air Pollution/*analysis ; Environment ; Environmental Exposure/*statistics & numerical data ; *Environmental Health ; Humans ; Risk ; Risk Factors ; }, } @article {pmid30459094, year = {2019}, author = {Pohlschroder, M and Schulze, S}, title = {Haloferax volcanii.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {86-87}, doi = {10.1016/j.tim.2018.10.004}, pmid = {30459094}, issn = {1878-4380}, abstract = {In this infographic we present the main tools available for the halophilic archaeon Haloferax volcanii, which have enabled successful research on its biology, including its genetics, proteostasis, cell surface structures, metabolic pathways, and adaptation to high salt environments. Isolated from the Dead Sea in 1975, Haloferax volcanii thrives in high salt environments and has emerged as an important archaeal model system. An extensive repertoire of genetic, molecular biological, and biochemical tools has been developed for this fast-growing, easily cultivated haloarchaeon, including expression vectors and gene-deletion strategies, including CRISPR. Its low mutation rate and ability to grow on defined media allow straightforward application of methods such as metabolic labeling, and the sequenced genome laid the foundation for transcriptomics and proteomics studies. These tools have allowed examination of key pathways such as transcription, noncoding RNAs, protein synthesis and degradation, protein glycosylation, motility, and biofilm formation. With the collaborative spirit of the H. volcanii community, this model system has become invaluable not only for enhancing our understanding of archaea but also for improving the development of biotech applications.}, } @article {pmid30459017, year = {2018}, author = {Fossheim, HJ}, title = {Past responsibility: History and the ethics of research on ethnic groups.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.shpsc.2018.11.003}, pmid = {30459017}, issn = {1879-2499}, abstract = {The article argues for the possibility of researchers' historical responsibility vis-à-vis ethnic groups. Such responsibility for a discipline's past transgressions is often attributed to anthropology, human genetics, parts of archaeology, and medicine, but without a clear conception of the nature of a responsibility supposedly going beyond the individual's own actions. Two concretizations are presented in order to show the fruitfulness and challenges of what I shall call a continuity approach: first, the case of the reburial of Sami human remains in Neiden, Norway; second, the use of the race concept in ethical and scientific contexts following the so-called New Synthesis in biology, which according to many marks a break with a racist past. Since no theory of researchers' historical responsibility towards ethnic groups exists, two partly relevant theories are brought in to provide a basis: Jenna Thompson's theory of nation states' responsibilities for past transgressions against peoples and a stance in political theory arguing that the beneficiary should pay even in cases where the beneficiary was not to blame for the original transgression. On this basis I sketch a continuity theory of historical responsibility, without which a notion of historical responsibility would be inapplicable in most actual cases.}, } @article {pmid30458867, year = {2018}, author = {Mukherjee, C and Beall, CJ and Griffen, AL and Leys, EJ}, title = {Correction to: High-resolution ISR amplicon sequencing reveals personalized oral microbiome.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {206}, doi = {10.1186/s40168-018-0594-1}, pmid = {30458867}, issn = {2049-2618}, abstract = {Following publication of the original article, the authors recognized that the left and right panels in Fig. 6b had been inadvertently switched during reformatting.}, } @article {pmid30458846, year = {2018}, author = {Gedif, G and Sisay, Y and Alebel, A and Belay, YA}, title = {Level of job satisfaction and associated factors among health care professionals working at University of Gondar Referral Hospital, Northwest Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {824}, pmid = {30458846}, issn = {1756-0500}, abstract = {OBJECTIVES: The main aim of this study was to assess the level of job satisfaction and associated factors among healthcare professionals working at University of Gondar Referral Hospital, Northwest Ethiopia. An institution based cross-sectional study was conducted among 416 healthcare professionals from March 27, 2017 to April 25, 2017. Simple random sampling technique was employed and data were collected with a pre-tested interviewer administered questionnaire. Data were entered into Epi-Info version 7, and analyzed using SPSS 20 softwares. Binary logistic regression analysis was employed.

RESULTS: A total of 383 participants were involved in the study. The overall level of job satisfaction among health care professionals was 54% [95% CI (49.3-58.8)]. Marital status [AOR = 1.79 (1.140, 2.797)], salary [AOR = 2.75 (1.269, 5.958)], leadership style [AOR = 2.19 (1.31-3.65)], and supportive supervision [AOR = 2.05 (1.27-3.32)] were found significant determinants of job satisfaction. The overall level of job satisfaction among health care professionals at the University of Gondar Referral Hospital was low. Therefore, health service managers should focus their leadership style and provide supportive supervision in the hospital to improve the level of job satisfaction of health care professionals.}, } @article {pmid30458842, year = {2018}, author = {Guyeux, C and Al-Nuaimi, B and AlKindy, B and Couchot, JF and Salomon, M}, title = {On the reconstruction of the ancestral bacterial genomes in genus Mycobacterium and Brucella.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {100}, pmid = {30458842}, issn = {1752-0509}, abstract = {BACKGROUND: To reconstruct the evolution history of DNA sequences, novel models of increasing complexity regarding the number of free parameters taken into account in the sequence evolution, as well as faster and more accurate algorithms, and statistical and computational methods, are needed. More particularly, as the principal forces that have led to major structural changes are genome rearrangements (such as translocations, fusions, and so on), understanding their underlying mechanisms, among other things via the ancestral genome reconstruction, are essential. In this problem, since finding the ancestral genomes that minimize the number of rearrangements in a phylogenetic tree is known to be NP-hard for three or more genomes, heuristics are commonly chosen to obtain approximations of the exact solution. The aim of this work is to show that another path is possible.

RESULTS: Various algorithms and software already deal with the difficult nature of the problem of reconstruction of the ancestral genome, but they do not function with precision, in particular when indels or single nucleotide polymorphisms fall into repeated sequences. In this article, and despite the theoretical NP-hardness of the ancestral reconstruction problem, we show that an exact solution can be found in practice in various cases, encompassing organelles and some bacteria. A practical example proves that an accurate reconstruction, which also allows to highlight homoplasic events, can be obtained. This is illustrated by the reconstruction of ancestral genomes of two bacterial pathogens, belonging in Mycobacterium and Brucella genera.

CONCLUSIONS: By putting together automatically reconstructed ancestral regions with handmade ones for problematic cases, we show that an accurate reconstruction of ancestors of the Brucella genus and of the Mycobacterium tuberculosis complex is possible. By doing so, we are able to investigate the evolutionary history of each pathogen by computing their common ancestors. They can be investigated extensively, by studying the gene content evolution over time, the resistance acquisition, and the impacts of mobile elements on genome plasticity.}, } @article {pmid30458828, year = {2018}, author = {Legeay, M and Aubourg, S and Renou, JP and Duval, B}, title = {Large scale study of anti-sense regulation by differential network analysis.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {95}, pmid = {30458828}, issn = {1752-0509}, abstract = {BACKGROUND: Systems biology aims to analyse regulation mechanisms into the cell. By mapping interactions observed in different situations, differential network analysis has shown its power to reveal specific cellular responses or specific dysfunctional regulations. In this work, we propose to explore on a large scale the role of natural anti-sense transcription on gene regulation mechanisms, and we focus our study on apple (Malus domestica) in the context of fruit ripening in cold storage.

RESULTS: We present a differential functional analysis of the sense and anti-sense transcriptomic data that reveals functional terms linked to the ripening process. To develop our differential network analysis, we introduce our inference method of an Extended Core Network; this method is inspired by C3NET, but extends the notion of significant interactions. By comparing two extended core networks, one inferred with sense data and the other one inferred with sense and anti-sense data, our differential analysis is first performed on a local view and reveals AS-impacted genes, genes that have important interactions impacted by anti-sense transcription. The motifs surrounding AS-impacted genes gather transcripts with functions mostly consistent with the biological context of the data used and the method allows us to identify new actors involved in ripening and cold acclimation pathways and to decipher their interactions. Then from a more global view, we compute minimal sub-networks that connect the AS-impacted genes using Steiner trees. Those Steiner trees allow us to study the rewiring of the AS-impacted genes in the network with anti-sense actors.

CONCLUSION: Anti-sense transcription is usually ignored in transcriptomic studies. The large-scale differential analysis of apple data that we propose reveals that anti-sense regulation may have an important impact in several cellular stress response mechanisms. Our data mining process enables to highlight specific interactions that deserve further experimental investigations.}, } @article {pmid30458802, year = {2018}, author = {Messina, A and Fiannaca, A and La Paglia, L and La Rosa, M and Urso, A}, title = {BioGraph: a web application and a graph database for querying and analyzing bioinformatics resources.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {98}, pmid = {30458802}, issn = {1752-0509}, abstract = {BACKGROUND: Several online databases provide a large amount of biomedical data of different biological entities. These resources are typically stored in systems implementing their own data model, user interface and query language. On the other hand, in many bioinformatics scenarios there is often the need to use more than one resource. The availability of a single bioinformatics platform that integrates many biological resources and services is, for those reasons a fundamental issue.

DESCRIPTION: Here, we present BioGraph, a web application that allows to query, visualize and analyze biological data belonging to several online available sources. BioGraph is built upon our previously developed graph database called BioGraphDB, that integrates and stores heterogeneous biological resources and make them available by means of a common structure and a unique query language. BioGraph implements state-of-the-art technologies and provides pre-compiled bioinformatics scenarios, as well as the possibility to perform custom queries and obtaining an interactive and dynamic visualization of results.

CONCLUSION: We present a case study about functional analysis of microRNA in breast cancer in order to demonstrate the functionalities of the system. BioGraph is freely available at http://biograph.pa.icar.cnr.it . Source files are available on GitHub at https://github.com/IcarPA-TBlab/BioGraph.}, } @article {pmid30458793, year = {2018}, author = {González-Menéndez, V and Martínez, G and Serrano, R and Muñoz, F and Martín, J and Genilloud, O and Tormo, JR}, title = {Ultraviolet (IUV) and mass spectrometry (IMS) imaging for the deconvolution of microbial interactions.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {99}, pmid = {30458793}, issn = {1752-0509}, abstract = {BACKGROUND: Spatial localization of natural products or proteins during microbial interactions can help to identify new antimicrobials both as offensive or defensive agents. Visible spatial interactions have been used for decades to enhance Drug Discovery processes both in industry and academia.

RESULTS: Herein we describe an automated micro-extraction methodology, that coupled with the previously described HPLC-Studio 2.0 software and the new development, the MASS-Studio 1.0 software, can combine multiple chemical analyses to generate ultraviolet (UV) and mass spectrometry (MS) images from traditional affordable analytical equipment. As a proof of concept, we applied this methodology on two microbial antagonisms observed among co-habitant endophytes isolated from endemic plants of arid areas of the south of Europe.

CONCLUSIONS: The use of UV and MS images highlighted interacting naturals products and allowed clear identification of induced molecules of interest not produced by the strains when cultured individually.}, } @article {pmid30458791, year = {2018}, author = {Hidalgo, JF and Egea, JA and Guil, F and García, JM}, title = {Improving the EFMs quality by augmenting their representativeness in LP methods.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {101}, pmid = {30458791}, issn = {1752-0509}, abstract = {BACKGROUND: Although cellular metabolism has been widely studied, its fully comprehension is still a challenge. A main tool for this study is the analysis of meaningful pieces of knowledge called modes and, in particular, specially interesting classes of modes such as pathways and Elementary Flux Modes (EFMs). Its study often has to deal with issues such as the appearance of infeasibilities or the difficulty of finding representative enough sets of modes that are free of repetitions. Mode extraction methods usually incorporate strategies devoted to mitigate this phenomena but they still get a high ratio of repetitions in the set of solutions.

RESULTS: This paper presents a proposal to improve the representativeness of the full set of metabolic reactions in the set of computed modes by penalizing the eventual high frequency of occurrence of some reactions during the extraction. This strategy can be applied to any linear programming based extraction existent method.

CONCLUSIONS: Our strategy enhances the quality of a set of extracted EFMs favouring the presence of every reaction in it and improving the efficiency by mitigating the occurrence of repeated solutions. The new proposed strategy can complement other EFMs extraction methods based on linear programming. The obtained solutions are more likely to be diverse using less computing effort and improving the efficiency of the extraction.}, } @article {pmid30458782, year = {2018}, author = {Valdés, MG and Galván-Femenía, I and Ripoll, VR and Duran, X and Yokota, J and Gavaldà, R and Rafael-Palou, X and de Cid, R}, title = {Pipeline design to identify key features and classify the chemotherapy response on lung cancer patients using large-scale genetic data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {97}, pmid = {30458782}, issn = {1752-0509}, abstract = {BACKGROUND: During the last decade, the interest to apply machine learning algorithms to genomic data has increased in many bioinformatics applications. Analyzing this type of data entails difficulties for managing high-dimensional data, class imbalance for knowledge extraction, identifying important features and classifying individuals. In this study, we propose a general framework to tackle these challenges with different machine learning algorithms and techniques. We apply the configuration of this framework on lung cancer patients, identifying genetic signatures for classifying response to drug treatment response. We intersect these relevant SNPs with the GWAS Catalog of the National Human Genome Research Institute and explore the Regulomedb, GTEx databases for functional analysis purposes.

RESULTS: The machine learning based solution proposed in this study is a scalable and flexible alternative to the classical uni-variate regression approach to analyze large-scale data. From 36 experiments executed using the machine learning framework design, we obtain good classification performance from the top 5 models with the highest cross-validation score and the smallest standard deviation. One thousand two hundred twenty four SNPs corresponding to the key features from the top 20 models (cross validation F1 mean >= 0.65) were compared with the GWAS Catalog finding no intersection with genome-wide significant reported hits. From these, new genetic signatures in MAE, CEP104, PRKCZ and ADRB2 show relevant biological regulatory functionality related to lung physiology.

CONCLUSIONS: We have defined a machine learning framework using data with an unbalanced large data-set of SNP-arrays and imputed genotyping data from a pharmacogenomics study in lung cancer patients subjected to first-line platinum-based treatment. This approach found genome signals with no genome-wide significance in the uni-variate regression approach (GWAS Catalog) that are valuable for classifying patients, only few of them with related biological function. The effect results of these variants can be explained by the recently proposed omnigenic model hypothesis, which states that complex traits can be influenced mostly by genes outside not only by the "core genes", mainly found by the genome-wide significant SNPs, but also by the rest of genes outside of the "core pathways" with apparent unrelated biological functionality.}, } @article {pmid30458775, year = {2018}, author = {Urda, D and Aragón, F and Bautista, R and Franco, L and Veredas, FJ and Claros, MG and Jerez, JM}, title = {BLASSO: integration of biological knowledge into a regularized linear model.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {94}, pmid = {30458775}, issn = {1752-0509}, abstract = {BACKGROUND: In RNA-Seq gene expression analysis, a genetic signature or biomarker is defined as a subset of genes that is probably involved in a given complex human trait and usually provide predictive capabilities for that trait. The discovery of new genetic signatures is challenging, as it entails the analysis of complex-nature information encoded at gene level. Moreover, biomarkers selection becomes unstable, since high correlation among the thousands of genes included in each sample usually exists, thus obtaining very low overlapping rates between the genetic signatures proposed by different authors. In this sense, this paper proposes BLASSO, a simple and highly interpretable linear model with l1-regularization that incorporates prior biological knowledge to the prediction of breast cancer outcomes. Two different approaches to integrate biological knowledge in BLASSO, Gene-specific and Gene-disease, are proposed to test their predictive performance and biomarker stability on a public RNA-Seq gene expression dataset for breast cancer. The relevance of the genetic signature for the model is inspected by a functional analysis.

RESULTS: BLASSO has been compared with a baseline LASSO model. Using 10-fold cross-validation with 100 repetitions for models' assessment, average AUC values of 0.7 and 0.69 were obtained for the Gene-specific and the Gene-disease approaches, respectively. These efficacy rates outperform the average AUC of 0.65 obtained with the LASSO. With respect to the stability of the genetic signatures found, BLASSO outperformed the baseline model in terms of the robustness index (RI). The Gene-specific approach gave RI of 0.15±0.03, compared to RI of 0.09±0.03 given by LASSO, thus being 66% times more robust. The functional analysis performed to the genetic signature obtained with the Gene-disease approach showed a significant presence of genes related with cancer, as well as one gene (IFNK) and one pseudogene (PCNAP1) which a priori had not been described to be related with cancer.

CONCLUSIONS: BLASSO has been shown as a good choice both in terms of predictive efficacy and biomarker stability, when compared to other similar approaches. Further functional analyses of the genetic signatures obtained with BLASSO has not only revealed genes with important roles in cancer, but also genes that should play an unknown or collateral role in the studied disease.}, } @article {pmid30458766, year = {2018}, author = {Rucci, E and Garcia, C and Botella, G and De Giusti, A and Naiouf, M and Prieto-Matias, M}, title = {SWIFOLD: Smith-Waterman implementation on FPGA with OpenCL for long DNA sequences.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {96}, pmid = {30458766}, issn = {1752-0509}, abstract = {BACKGROUND: The Smith-Waterman (SW) algorithm is the best choice for searching similar regions between two DNA or protein sequences. However, it may become impracticable in some contexts due to its high computational demands. Consequently, the computer science community has focused on the use of modern parallel architectures such as Graphics Processing Units (GPUs), Xeon Phi accelerators and Field Programmable Gate Arrays (FGPAs) to speed up large-scale workloads.

RESULTS: This paper presents and evaluates SWIFOLD: a Smith-Waterman parallel Implementation on FPGA with OpenCL for Long DNA sequences. First, we evaluate its performance and resource usage for different kernel configurations. Next, we carry out a performance comparison between our tool and other state-of-the-art implementations considering three different datasets. SWIFOLD offers the best average performance for small and medium test sets, achieving a performance that is independent of input size and sequence similarity. In addition, SWIFOLD provides competitive performance rates in comparison with GPU-based implementations on the latest GPU generation for the large dataset.

CONCLUSIONS: The results suggest that SWIFOLD can be a serious contender for accelerating the SW alignment of DNA sequences of unrestricted size in an affordable way reaching on average 125 GCUPS and almost a peak of 270 GCUPS.}, } @article {pmid30458763, year = {2018}, author = {Papacek, S and Jablonsky, J and Petera, K}, title = {Advanced integration of fluid dynamics and photosynthetic reaction kinetics for microalgae culture systems.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 5}, pages = {93}, pmid = {30458763}, issn = {1752-0509}, abstract = {BACKGROUND: Photosynthetic microalgae have been in the spotlight of biotechnological production (biofuels, lipids, etc), however, current barriers in mass cultivation of microalgae are limiting its successful industrialization. Therefore, a mathematical model integrating both the biological and hydrodynamical parts of the cultivation process may improve our understanding of relevant phenomena, leading to further optimization of the microalgae cultivation.

RESULTS: We introduce a unified multidisciplinary simulation tool for microalgae culture systems, particularly the photobioreactors. Our approach describes changes of cell growth determined by dynamics of heterogeneous environmental conditions such as irradiation and mixing of the culture. Presented framework consists of (i) a simplified model of microalgae growth in a culture system (the advection-diffusion-reaction system within a phenomenological model of photosynthesis and photoinhibition), (ii) the fluid dynamics (Navier-Stokes equations), and (iii) the irradiance field description (Beer-Lambert law). To validate the method, a simple case study leading to hydrodynamically induced fluctuating light conditions was chosen. The integration of computational fluid dynamics (ANSYS Fluent) revealed the inner property of the system, the flashing light enhancement phenomenon, known from experiments.

CONCLUSION: Our physically accurate model of microalgae culture naturally exhibits features of real system, can be applied to any geometry of microalgae mass cultivation and thus is suitable for biotechnological applications.}, } @article {pmid30458760, year = {2018}, author = {Qin, W and Lu, X and Liu, Y and Bai, H and Li, S and Lin, S}, title = {Precise A•T to G•C base editing in the zebrafish genome.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {139}, pmid = {30458760}, issn = {1741-7007}, abstract = {BACKGROUND: Base editors are a class of genome editing tools with the ability to efficiently induce point mutations in genomic DNA, without inducing double-strand breaks or relying on homology-direct repair as in other such technologies. Recently, adenine base editors (ABEs) have been developed to mediate the conversion of A•T to G•C in genomic DNA of human cells, mice, and plants. Here, we investigated the activity and efficiency of several adenine base editors in zebrafish and showed that base editing can be used to create new models of pathogenic diseases caused by point mutations.

RESULTS: The original ABE7.10 exhibits almost no activity in zebrafish. After codon optimization, we found that a zABE7.10 variant could induce targeted conversion of adenine to guanine in zebrafish at multiple tested genomic loci, and all the target sites showed a high rate of germline targeting efficiency. Furthermore, using this system, we established a zebrafish model of 5q-Syndrome that contained a new point mutation in rps14. The further modification of zABE7.10 by a bipartite nuclear localization signals (bpNLS) resulted in 1.96-fold average improvement in ABE-mediated editing efficiency at four sites.

CONCLUSIONS: Collectively, this system, designated as zABE7.10, provides a strategy to perform A•T to G•C base editing in zebrafish and enhances its capacity to model human diseases.}, } @article {pmid30458749, year = {2018}, author = {Glatthorn, J and Feldmann, E and Tabaku, V and Leuschner, C and Meyer, P}, title = {Classifying development stages of primeval European beech forests: is clustering a useful tool?.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {47}, pmid = {30458749}, issn = {1472-6785}, support = {-//Stemmler Foundation/ ; }, abstract = {BACKGROUND: Old-growth and primeval forests are passing through a natural development cycle with recurring stages of forest development. Several methods for assigning patches of different structure and size to forest development stages or phases do exist. All currently existing classification methods have in common that a priori assumptions about the characteristics of certain stand structural attributes such as deadwood amount are made. We tested the hypothesis that multivariate datasets of primeval beech forest stand structure possess an inherent, aggregated configuration of data points with individual clusters representing forest development stages. From two completely mapped primeval beech forests in Albania, seven ecologically important stand structural attributes characterizing stand density, regeneration, stem diameter variation and amount of deadwood are derived at 8216 and 9666 virtual sampling points (moving window, focal filtering). K-means clustering is used to detect clusters in the datasets (number of clusters (k) between 2 and 5). The quality of the single clustering solutions is analyzed with average silhouette width as a measure for clustering quality. In a sensitivity analysis, clustering is done with datasets of four different spatial scales of observation (200, 500, 1000 and 1500 m2, circular virtual plot area around sampling points) and with two different kernels (equal weighting of all objects within a plot vs. weighting by distance to the virtual plot center).

RESULTS: The clustering solutions succeeded in detecting and mapping areas with homogeneous stand structure. The areas had extensions of more than 200 m2, but differences between clusters were very small with average silhouette widths of less than 0.28. The obtained datasets had a homogeneous configuration with only very weak trends for clustering.

CONCLUSIONS: Our results imply that forest development takes place on a continuous scale and that discrimination between development stages in primeval beech forests is splitting continuous datasets at selected thresholds. For the analysis of the forest development cycle, direct quantification of relevant structural features or processes might be more appropriate than classification. If, however, the study design demands classification, our results can justify the application of conventional forest development stage classification schemes rather than clustering.}, } @article {pmid30458731, year = {2018}, author = {Zeng, R and Gao, S and Xu, L and Liu, X and Dai, F}, title = {Prediction of pathogenesis-related secreted proteins from Stemphylium lycopersici.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {191}, pmid = {30458731}, issn = {1471-2180}, support = {2016YFD0201008//The National Key Research and Development Program of China/ ; 20160119//The Youth Talent Development Plan of Shanghai Municipal Agricultural System/ ; 2018(B-01)//SAAS Program for Excellent Research Team/ ; 16ZR1424100//Sponsored by Natural Science Foundation of Shanghai/ ; }, abstract = {BACKGROUND: Gray leaf spot is a devastating disease caused by Stemphylium lycopersici that threatens tomato-growing areas worldwide. Typically, many pathogenesis-related and unrelated secreted proteins can be predicted in genomes using bioinformatics and computer-based prediction algorithms, which help to elucidate the molecular mechanisms of pathogen-plant interactions.

RESULTS: S. lycopersici-secreted proteins were predicted from 8997 proteins using a set of internet-based programs, including SignalP v4.1 TMHMM v2.0, big-PI Fungal Predictor, ProtComp V9.0 and TargetP v1.1. Analysis showed that 511 proteins are predicted to be secreted. These proteins vary from 51 to 600 residues in length, with signal peptides ranging from 14 to 30 residues in length. Functional analysis of differentially expressed proteins was performed using Blast2GO. Gene ontology analysis of 305 proteins classified them into 8 groups in biological process (BP), 6 groups in molecular function (MF), and 10 groups in cellular component (CC). Pathogen-host interaction (PHI) partners were predicted by performing BLASTp analysis of the predicted secreted proteins against the PHI database. In total, 159 secreted proteins in S. lycopersici might be involved in pathogenicity and virulence pathways. Scanning S. lycopersici-secreted proteins for the presence of carbohydrate-active enzyme (CAZyme)-coding gene homologs resulted in the prediction of 259 proteins. In addition, 12 of the 511 proteins predicted to be secreted are small cysteine-rich proteins (SCRPs).

CONCLUSIONS: S. lycopersici secretory proteins have not yet been studied. The study of S. lycopersici genes predicted to encode secreted proteins is highly significant for research aimed at understanding the hypothesized roles of these proteins in host penetration, tissue necrosis, immune subversion and the identification of new targets for fungicides.}, } @article {pmid30458728, year = {2018}, author = {Vieira, VMNCS and Engelen, AH and Huanel, OR and Guillemin, ML}, title = {Haploid females in the isomorphic biphasic life-cycle of Gracilaria chilensis excel in survival.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {174}, pmid = {30458728}, issn = {1471-2148}, mesh = {Chile ; Ecosystem ; Fertility ; Gracilaria/*growth & development ; *Haploidy ; *Life Cycle Stages ; Probability ; Seasons ; }, abstract = {BACKGROUND: Conditional differentiation is one of the most fundamental drivers of biodiversity. Competitive entities (usually species) differ in environmental or ecological niche enabling them to co-exist. Conditional differentiation of haploid and diploid generations is considered to be a requirement for the evolutionary stability of isomorphic biphasic life-cycles and the cause for the natural occurrence of both phases at uneven abundances. Theoretically, stage dependent survival rates are the most efficient way to explain conditional differentiation.

RESULTS: We tested for conditional differentiation in survival rates among life stages (haploid males, haploid females, and diploids) of Gracilaria chilensis, an intertidal red alga occurring along the Chilean shores. Therefore, the fate of individuals was followed periodically for 3 years in five intertidal pools and, for the first time in isomorphic red algae, a composite model of the instantaneous survival rates was applied. The results showed the survival dependency on density (both competition and Allee effects), fertility, age, size, season and location, as well as the differentiation among stages for the survival dependencies of these factors. The young haploid females survived more than the young of the other stages under Allee effects during the environmentally stressful season at the more exposed locations, and under self-thinning during the active growth season. Furthermore, fertile haploid females had a higher survival than fertile haploid males or fertile diploids.

CONCLUSIONS: Here, we show a survival advantage of haploids over diploids. The haploid females probably optimize their resource management targeting structural and physiological adaptations that significantly enhance survival under harsher conditions. In a companion paper we demonstrate a fertility advantage of diploids over haploids. Together, the survival and fertility differentiation support the evolution and prevalence of biphasic life-cycles.}, } @article {pmid30458726, year = {2018}, author = {Rodríguez, FE and Laporte, D and González, A and Mendez, KN and Castro-Nallar, E and Meneses, C and Huidobro-Toro, JP and Moenne, A}, title = {Copper-induced increased expression of genes involved in photosynthesis, carotenoid synthesis and C assimilation in the marine alga Ulva compressa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {829}, pmid = {30458726}, issn = {1471-2164}, support = {Fondecyt 1160013//CONICYT/ ; Postdoctoral Fondecyt 3170511//CONICYT/ ; Postdoctoral DICYT//Universidad de Santiago de Chile/ ; }, abstract = {BACKGROUND: The marine alga Ulva compressa is the dominant species in coastal areas receiving effluents from copper mines. The alga can accumulate high amounts of copper and possesses a strong antioxidant system. Here, we performed short-term transcriptomic analyses using total RNA of the alga cultivated with 10 μM of copper for 0, 3, 6, 12 and 24 h by RNA-seq.

RESULTS: De novo transcriptomes were assembled using the Trinity software, putative proteins were annotated and classified using Blast2GO. Differentially expressed transcripts were identified using edgeR. Transcript levels were compared by paired times 0 vs 3, 0 vs 6, 0 vs 12 and 0 vs 24 h at an FDR < 0.01 and Log2 Fold Change > 2. Up-regulated transcripts encode proteins belonging to photosystem II (PSII), Light Harvesting II Complex (LHCII), PSI and LHCI, proteins involved in assembly and repair of PSII, and assembly and protection of PSI. In addition, transcripts encoding enzymes leading to β-carotene synthesis and enzymes belonging to the Calvin-Benson cycle were also increased. We further analyzed photosynthesis and carotenoid levels in the alga cultivated with 10 μM of copper for 0 to 24 h. Photosynthesis was increased from 3 to 24 h as well as the level of total carotenoids. The increase in transcripts encoding enzymes of the Calvin-Benson cycle suggests that C assimilation may also be increased.

CONCLUSIONS: Thus, U. compressa displays a short-term response to copper stress enhancing the expression of genes encoding proteins involved in photosynthesis, enzymes involved carotenoids synthesis, as well as those belonging to the Calvin-Benson cycle, which may result in an increase in C assimilation.}, } @article {pmid30458725, year = {2018}, author = {Denti, L and Rizzi, R and Beretta, S and Vedova, GD and Previtali, M and Bonizzoni, P}, title = {ASGAL: aligning RNA-Seq data to a splicing graph to detect novel alternative splicing events.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {444}, pmid = {30458725}, issn = {1471-2105}, support = {2013--0955//Fondazione Cariplo (IT)/ ; }, mesh = {Alternative Splicing/*genetics ; Humans ; RNA/*genetics ; RNA Splicing/*genetics ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: While the reconstruction of transcripts from a sample of RNA-Seq data is a computationally expensive and complicated task, the detection of splicing events from RNA-Seq data and a gene annotation is computationally feasible. This latter task, which is adequate for many transcriptome analyses, is usually achieved by aligning the reads to a reference genome, followed by comparing the alignments with a gene annotation, often implicitly represented by a graph: the splicing graph.

RESULTS: We present ASGAL (Alternative Splicing Graph ALigner): a tool for mapping RNA-Seq data to the splicing graph, with the specific goal of detecting novel splicing events, involving either annotated or unannotated splice sites. ASGAL takes as input the annotated transcripts of a gene and a RNA-Seq sample, and computes (1) the spliced alignments of each read in input, and (2) a list of novel events with respect to the gene annotation.

CONCLUSIONS: An experimental analysis shows that ASGAL allows to enrich the annotation with novel alternative splicing events even when genes in an experiment express at most one isoform. Compared with other tools which use the spliced alignment of reads against a reference genome for differential analysis, ASGAL better predicts events that use splice sites which are novel with respect to a splicing graph, showing a higher accuracy. To the best of our knowledge, ASGAL is the first tool that detects novel alternative splicing events by directly aligning reads to a splicing graph.

AVAILABILITY: Source code, documentation, and data are available for download at http://asgal.algolab.eu .}, } @article {pmid30458720, year = {2018}, author = {Wang, WL and Wang, YX and Li, H and Liu, ZW and Cui, X and Zhuang, J}, title = {Two MYB transcription factors (CsMYB2 and CsMYB26) are involved in flavonoid biosynthesis in tea plant [Camellia sinensis (L.) O. Kuntze].}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {288}, pmid = {30458720}, issn = {1471-2229}, support = {31570691//National Natural Science Foundation of China/ ; }, mesh = {Abscisic Acid/metabolism ; Amino Acid Motifs ; Camellia sinensis/*metabolism ; Cloning, Molecular ; Conserved Sequence ; Flavonoids/*biosynthesis ; Gene Expression Regulation, Plant ; Genes, Plant ; Plant Leaves/metabolism ; Plant Proteins/genetics/*metabolism ; Promoter Regions, Genetic ; Transcription Factors/genetics/*metabolism ; }, abstract = {BACKGROUND: Flavonoids are secondary metabolites that play important roles in the entire tea plant life cycle and have potential health-promoting properties. MYB transcription factors (TFs) are considered potentially important regulators of flavonoid biosynthesis in plants. However, the molecular mechanisms by which MYB TFs regulate the flavonoid pathway in tea plant remain unknown.

RESULTS: In this study, two R2R3-MYB TFs (CsMYB2 and CsMYB26) involved in flavonoid biosynthesis in tea plant were investigated. The genes encoding CsMYB2 and CsMYB26 were cloned from the tea plant cultivar 'Longjing 43'. Phylogenetic analysis showed that CsMYB2 and CsMYB26 were grouped into the proanthocyanidin biosynthesis-related MYB clade. Multiple sequence alignment revealed that conserved motif 1 in the two MYB factors was related to the bHLH TF. Subcellular localization assays suggested that CsMYB2 localized in the nucleus. Promoter analysis indicated that CsMYB2, CsMYB26 and the related structural genes contain MYB recognition elements. The expression levels of the CsMYB2 and CsMYB26 genes and the structural genes in the flavonoid biosynthesis pathway were determined in leaves from various sites in the two tea plant cultivars 'Longjing 43' and 'Baiye 1 hao'.

CONCLUSIONS: The expression levels of these genes were correlated with the accumulated flavonoid content. The results demonstrated that the expression level of CsF3'H may be regulated by CsMYB2 and that CsMYB26 expression is positively correlated with CsLAR expression. The relative transcriptional level of CsMYB26 may be the main reason for the different epigallocatechin contents between the tea plant cultivars 'Longjing 43' and 'Baiye 1 hao'. Our results will serve as a reference for the potential regulatory roles of CsMYB2 and CsMYB26 in flavonoid biosynthesis in tea plant and may also assist biologists in improving tea quality.}, } @article {pmid30458716, year = {2018}, author = {Takagi, H and Watanabe, S and Tanaka, S and Matsuura, T and Mori, IC and Hirayama, T and Shimada, H and Sakamoto, A}, title = {Disruption of ureide degradation affects plant growth and development during and after transition from vegetative to reproductive stages.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {287}, pmid = {30458716}, issn = {1471-2229}, support = {25119717//Ministry of Education, Culture, Sports, Science and Technology/ ; 26440147//Japan Society for the Promotion of Science/ ; 26-5367//Japan Society for the Promotion of Science/ ; }, mesh = {Allantoin/*metabolism ; Amidohydrolases/genetics/metabolism ; Arabidopsis/enzymology/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/metabolism ; Mutation ; Nitrogen/metabolism ; Ureohydrolases/genetics/metabolism ; }, abstract = {BACKGROUND: The ureides allantoin and allantoate are major metabolic intermediates of purine catabolism with high nitrogen-to-carbon ratios. Ureides play a key role in nitrogen utilization in ureide-type legumes, but their effects on growth and development in non-legume plants are poorly understood. Here, we examined the effects of knocking out genes encoding ureide-degrading enzymes, allantoinase (ALN) and allantoate amidohydrolase (AAH), on the vegetative-to-reproductive transition and subsequent growth of Arabidopsis plants.

RESULTS: The ureide-degradation mutants (aln and aah) showed symptoms similar to those of nitrogen deficiency: early flowering, reduced size at maturity, and decreased fertility. Consistent with these phenotypes, carbon-to-nitrogen ratios and nitrogen-use efficiencies were significantly decreased in ureide-degradation mutants; however, adding nitrogen to irrigation water did not alleviate the reduced growth of these mutants. In addition to nitrogen status, levels of indole-3-acetic acid and gibberellin in five-week-old plants were also affected by the aln mutations. To test the possibility that ureides are remobilized from source to sink organs, we measured ureide levels in various organs. In wild-type plants, allantoate accumulated predominantly in inflorescence stems and siliques; this accumulation was augmented by disruption of its catabolism. Mutants lacking ureide transporters, ureide permeases 1 and 2 (UPS1 and UPS2), exhibited phenotypes similar to those of the ureide-degradation mutants, but had decreased allantoate levels in the reproductive organs. Transcript analysis in wild-type plants suggested that genes involved in allantoate synthesis and ureide transport were coordinately upregulated in senescing leaves.

CONCLUSIONS: This study demonstrates that ureide degradation plays an important role in supporting healthy growth and development in non-legume Arabidopsis during and after transition from vegetative to reproductive stages.}, } @article {pmid30458713, year = {2018}, author = {Mannion, A and Shen, Z and Fox, JG}, title = {Comparative genomics analysis to differentiate metabolic and virulence gene potential in gastric versus enterohepatic Helicobacter species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {830}, pmid = {30458713}, issn = {1471-2164}, support = {R35-CA210088//National Institutes of Health/ ; T32-OD010978//National Institutes of Health/ ; R35 CA210088/CA/NCI NIH HHS/United States ; P30-ES002109//National Institutes of Health/ ; P30 ES002109/ES/NIEHS NIH HHS/United States ; T32 OD010978/OD/NIH HHS/United States ; P01-CA028848//National Institutes of Health/ ; }, abstract = {BACKGROUND: The genus Helicobacter are gram-negative, microaerobic, flagellated, mucus-inhabiting bacteria associated with gastrointestinal inflammation and classified as gastric or enterohepatic Helicobacter species (EHS) according to host species and colonization niche. While there are over 30 official species, little is known about the physiology and pathogenic mechanisms of EHS, which account for most in the genus, as well as what genetic factors differentiate gastric versus EHS, given they inhabit different hosts and colonization niches. The objective of this study was to perform a whole-genus comparative analysis of over 100 gastric versus EHS genomes in order to identify genetic determinants that distinguish these Helicobacter species and provide insights about their evolution/adaptation to different hosts, colonization niches, and mechanisms of virulence.

RESULTS: Whole-genome phylogeny organized Helicobacter species according to their presumed gastric or EHS classification. Analysis of orthologs revealed substantial heterogeneity in physiological and virulence-related genes between gastric and EHS genomes. Metabolic reconstruction predicted that unlike gastric species, EHS appear asaccharolytic and dependent on amino/organic acids to fuel metabolism. Additionally, gastric species lack de novo biosynthetic pathways for several amino acids and purines found in EHS and instead rely on environmental uptake/salvage pathways. Comparison of virulence factor genes between gastric and EHS genomes identified overlapping yet distinct profiles and included canonical cytotoxins, outer membrane proteins, secretion systems, and survival factors.

CONCLUSIONS: The major differences in predicted metabolic function suggest gastric species and EHS may have evolved for survival in the nutrient-rich stomach versus the nutrient-devoid environments, respectively. Contrasting virulence factor gene profiles indicate gastric species and EHS may utilize different pathogenic mechanisms to chronically infect hosts and cause inflammation and tissue damage. The findings from this study provide new insights into the genetic differences underlying gastric versus EHS and support the need for future experimental studies to characterize these pathogens.}, } @article {pmid30458712, year = {2018}, author = {Filippi-Codaccioni, O and Beugin, MP and de Vienne, DM and Portanier, E and Fouchet, D and Kaerle, C and Muselet, L and Queney, G and Petit, EJ and Regis, C and Pons, JB and Pontier, D}, title = {Coexistence of two sympatric cryptic bat species in French Guiana: insights from genetic, acoustic and ecological data.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {175}, pmid = {30458712}, issn = {1471-2148}, mesh = {*Acoustics ; Animals ; Cell Nucleus/genetics ; Chiroptera/anatomy & histology/*genetics ; Echolocation ; *Ecosystem ; French Guiana ; Genotype ; Microsatellite Repeats/genetics ; Reproduction ; Species Specificity ; Sympatry/*physiology ; }, abstract = {BACKGROUND: The distinction between lineages of neotropical bats from the Pteronotus parnellii species complex has been previously made according to mitochondrial DNA, and especially morphology and acoustics, in order to separate them into two species. In these studies, either sample sizes were too low when genetic and acoustic or morphological data were gathered on the same individuals, or genetic and other data were collected on different individuals. In this study, we intensively sampled bats in 4 caves and combined all approaches in order to analyse genetic, morphologic, and acoustic divergence between these lineages that live in the same caves in French Guiana.

RESULTS: A multiplex of 20 polymorphic microsatellite markers was developed using the 454-pyrosequencing technique to investigate for the first time the extent of reproductive isolation between the two lineages and the population genetic structure within lineages. We genotyped 748 individuals sampled between 2010 and 2015 at the 20 nuclear microsatellite loci and sequenced a portion of the cytochrome c oxydase I gene in a subset of these. Two distinct, non-overlapping haplogroups corresponding to cryptic species P. alitonus and P. rubiginosus were revealed, in accordance with previous findings. No spatial genetic structure between caves was detected for both species. Hybridization appeared to be quite limited (0.1-4%) using microsatellite markers whereas introgression was more common (7.5%) and asymmetric for mitochondrial DNA (mtDNA).

CONCLUSIONS: The extremely low rate of hybridization could be explained by differences in life cycle phenology between species as well as morphological and acoustical distinction between sexes in one or the other species. Taken together, these results add to our growing understanding of the nature of species boundaries in Pteronotus parnelli, but deserve more in-depth studies to understand the evolutionary processes underlying asymmetric mtDNA introgression in this group of cryptic species.}, } @article {pmid30458711, year = {2018}, author = {Ma, Y and Feng, S and Wang, X and Qazi, IH and Long, K and Luo, Y and Li, G and Ning, C and Wang, Y and Hu, S and Xiao, J and Li, X and Lan, D and Hu, Y and Tang, Q and Ma, J and Jin, L and Jiang, A and Li, M}, title = {Exploration of exosomal microRNA expression profiles in pigeon 'Milk' during the lactation period.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {828}, pmid = {30458711}, issn = {1471-2164}, support = {31472081//the National Natural Science Foundation of China/ ; 31522055//the National Natural Science Foundation of China/ ; 2016JY0167//the Application Basic Research Plan Project of Sichuan Province/ ; 2017JZ0025//the Sichuan Province & Chinese Academy of Science & Technology Cooperation Project/ ; }, abstract = {BACKGROUND: Pigeon crop has the unique ability to produce a nutrient rich substance termed pigeon 'milk' (PM), which has functional resemblance with the mammalian milk. Previous researches have demonstrated that a large number of exosomes and exosomal miRNAs exist in mammalian milk, and many of them are associated with immunity, growth and development. However, to date, little is known about the exosomes and exosomal miRNAs in PM.

RESULTS: In this study, we isolated the exosomes from PM and used small RNA sequencing to investigate the distribution and expression profiles of exosomal miRNAs. A total of 301 mature miRNAs including 248 conserved and 53 novel miRNAs were identified in five lactation stages i.e. 1d, 5d, 10d, 15d, and 20d. From these, four top 10 conserved miRNAs (cli-miR-21-5p, cli-miR-148a-3p, cli-miR-10a-5p and cli-miR-26a-5p) were co-expressed in all five stages. We speculate that these miRNAs may have important role in the biosynthesis and metabolism of PM. Moreover, similar to the mammalian milk, a significant proportion of immune and growth-related miRNAs were also present and enriched in PM exosomes. Furthermore, we also identified 41 orthologous miRNAs group (giving rise to 81 mature miRNA) commonly shared with PM, human, bovine and porcine breast milk. Additionally, functional enrichment analysis revealed the role of exosomal miRNAs in organ development and in growth-related pathways including the MAPK, Wnt and insulin pathways.

CONCLUSIONS: To sum-up, this comprehensive analysis will contribute to a better understanding of the underlying functions and regulatory mechanisms of PM in squabs.}, } @article {pmid30458710, year = {2018}, author = {Liu, D and Teng, Z and Kong, J and Liu, X and Wang, W and Zhang, X and Zhai, T and Deng, X and Wang, J and Zeng, J and Xiao, Y and Guo, K and Zhang, J and Liu, D and Wang, W and Zhang, Z}, title = {Natural variation in a CENTRORADIALIS homolog contributed to cluster fruiting and early maturity in cotton.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {286}, pmid = {30458710}, issn = {1471-2229}, support = {2016YFD0100203-2//National Key Research and Development Program of China/ ; 31701471//National Science Foundation of China/ ; 31460363//National Science Foundation of China/ ; }, mesh = {Flowers/genetics ; Fruit/growth & development ; Gene Expression ; *Genes, Plant ; *Genetic Variation ; Gossypium/*genetics/growth & development ; Mutation ; Plant Breeding ; }, abstract = {BACKGROUND: Plant architecture and the vegetative-reproductive transition have major impacts on the agronomic success of crop plants, but genetic mechanisms underlying these traits in cotton (Gossypium spp.) have not been identified.

RESULTS: We identify four natural mutations in GoCEN-Dt associated with cluster fruiting (cl) and early maturity. The situ hybridization shows that GhCEN is preferentially expressed in cotton shoot apical meristems (SAM) of the main stem and axillary buds. Constitutive GhCEN-Dt overexpression suppresses the transition of the cotton vegetative apex to a reproductive shoot. Silencing GoCEN leads to early flowering and determinate growth, and in tetraploids causes the main stem to terminate in a floral bud, a novel phenotype that exemplifies co-adaptation of polyploid subgenomes and suggests new research and/or crop improvement approaches. Natural cl variations are enriched in cottons adapted to high latitudes with short frost-free periods, indicating that mutants of GoCEN have been strongly selected for early maturity.

CONCLUSION: We show that the cotton gene GoCEN-Dt, a homolog of Antirrhinum CENTRORADIALIS, is responsible for determinate growth habit and cluster fruiting. Insight into the genetic control of branch and flower differentiation offers new approaches to develop early maturing cultivars of cotton and other crops with plant architecture appropriate for mechanical harvesting.}, } @article {pmid30458708, year = {2018}, author = {Rončević, T and Gerdol, M and Spazzali, F and Florian, F and Mekinić, S and Tossi, A and Pallavicini, A}, title = {Parallel identification of novel antimicrobial peptide sequences from multiple anuran species by targeted DNA sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {827}, pmid = {30458708}, issn = {1471-2164}, support = {8481//Hrvatska Zaklada za Znanost/ ; 2181-202-02-07-17-0149//Erasmus+/ ; 2181-202-01-01-17-0028//Student Quorum University of Split/ ; }, abstract = {BACKGROUND: Antimicrobial peptides (AMPs) are multifunctional effector molecules that often combine direct antimicrobial activities with signaling or immunomodulatory functions. The skin secretions of anurans contain a variety of such bioactive peptides. The identification of AMPs from frog species often requires sacrificing several specimens to obtain small quantities of crude peptides, followed by activity based fractionation to identify the active principles.

RESULTS: We report an efficient alternative approach to selectively amplify AMP-coding transcripts from very small amounts of tissue samples, based on RNA extraction and cDNA synthesis, followed by PCR amplification and high-throughput sequencing of size-selected amplicons. This protocol exploits the highly conserved signal peptide region of the AMP precursors from Ranidae, Hylidae and Bombinatoridae for the design of family-specific, forward degenerate primers, coupled with a reverse primer targeting the mRNA poly-A tail.

CONCLUSIONS: Analysis of the assembled sequencing output allowed to identify more than a hundred full-length mature peptides, mostly from Ranidae species, including several novel potential AMPs for functional characterization. This (i) confirms the effectiveness of the experimental approach and indicates points for protocol optimization to account for particular cases, and (ii) encourages the application of the same methodology to other multigenic AMP families, also from other genera, sharing common features as in anuran AMPs.}, } @article {pmid30458707, year = {2018}, author = {Lewis, TR and Kundinger, SR and Link, BA and Insinna, C and Besharse, JC}, title = {Kif17 phosphorylation regulates photoreceptor outer segment turnover.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {25}, pmid = {30458707}, issn = {1471-2121}, support = {R01 EY014167/EY/NEI NIH HHS/United States ; R01 EY003222/EY/NEI NIH HHS/United States ; R01 EY03222//National Eye Institute/ ; R01 EY014167//National Eye Institute/ ; P30 EY001931//National Eye Institute/ ; T32 EY014537/EY/NEI NIH HHS/United States ; T32 EY014537//National Eye Institute/ ; P30 EY001931/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: KIF17, a kinesin-2 motor that functions in intraflagellar transport, can regulate the onset of photoreceptor outer segment development. However, the function of KIF17 in a mature photoreceptor remains unclear. Additionally, the ciliary localization of KIF17 is regulated by a C-terminal consensus sequence (KRKK) that is immediately adjacent to a conserved residue (mouse S1029/zebrafish S815) previously shown to be phosphorylated by CaMKII. Yet, whether this phosphorylation can regulate the localization, and thus function, of KIF17 in ciliary photoreceptors remains unknown.

RESULTS: Using transgenic expression in zebrafish photoreceptors, we show that phospho-mimetic KIF17 has enhanced localization along the cone outer segment. Importantly, expression of phospho-mimetic KIF17 is associated with greatly enhanced turnover of the photoreceptor outer segment through disc shedding in a cell-autonomous manner, while genetic mutants of kif17 in zebrafish and mice have diminished disc shedding. Lastly, cone expression of constitutively active tCaMKII leads to a kif17-dependent increase in disc shedding.

CONCLUSIONS: Taken together, our data support a model in which phosphorylation of KIF17 promotes its photoreceptor outer segment localization and disc shedding, a process essential for photoreceptor maintenance and homeostasis. While disc shedding has been predominantly studied in the context of the mechanisms underlying phagocytosis of outer segments by the retinal pigment epithelium, this work implicates photoreceptor-derived signaling in the underlying mechanisms of disc shedding.}, } @article {pmid30458706, year = {2018}, author = {Zhang, C and Yu, D and Ke, F and Zhu, M and Xu, J and Zhang, M}, title = {Seedless mutant 'Wuzi Ougan' (Citrus suavissima Hort. ex Tanaka 'seedless') and the wild type were compared by iTRAQ-based quantitative proteomics and integratedly analyzed with transcriptome to improve understanding of male sterility.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {106}, pmid = {30458706}, issn = {1471-2156}, support = {LGN18C160005//Zhejiang Province Public Welfare Technology Application Research Project (CN)/ ; 31000897//National Natural Science Foundation of China (CN)/ ; 31301811//The National Natural Science Foundation of China/ ; 2016C02052-1//Department of Science and Technology of Zhejiang Province (CN)/ ; CARS-27//Earmarked Fund for China Agriculture Research System (CN)/ ; }, abstract = {BACKGROUND: Bud mutation is a vital method of citrus. 'Wuzi Ougan' (mutant type, MT) as a bud variant of 'Ougan' (wild type, WT) was first found in 1996 and has become popular because of its male sterility and seedless character. Previous analysis of its cytological sections and transcriptome revealed that the abnormal microsporogenesis that occurs before the tetrad stage of anther development might be the result of down-regulated oxidation-reduction biological processes in MT. To reveal the mechanism behind the male sterility in MT at the post-transcriptional stage, proteome profiling and integrative analysis on previously obtained transcriptome and proteome data were performed in two strains.

RESULTS: The proteome profiling was performed by iTRAQ (isobaric Tags for relative and absolute quantitation) analysis and 6201 high-confidence proteins were identified, among which there were 487 differentially expressed proteins (DEPs) in one or more developmental stages of anthers between MT and WT. The main functional subcategories associated with the main category biological process into which the DEPs were classified were sporopollenin biosynthesis process and pollen exine formation. The enriched pathways were phenylpropanoid biosynthesis, flavonoid biosynthesis, and phenylalanine metabolism. Moreover, there were eight pathways linked in terms of being related to phenylpropanoid metabolism. Eighteen important genes related to phenylpropanoid metabolism were also analysized by qRT-PCR (quantitative real time PCR). An integrative analysis of the fold change at the transcript (log2 FPKM ratios) and protein (log1.2 iTRAQ ratios) levels was performed to reveal the consistency of gene expression at transcriptional and proteomic level. In general, the expression of genes and proteins tended to be positively correlated, in which the correlation coefficients were 0.3414 (all genes and all proteins) and 0.5686 (DEPs and according genes).

CONCLUSION: This study is the first to offer a comprehensive understanding of the gene regulation in 'Wuzi Ougan' and its wild type, especially during the microsporocyte to meiosis stage. Specifically, the involved genes include those in phenylpropanoid biosynthesis, flavonoid biosynthesis, and phenylalanine metabolism, as determined by integrative transcriptome and proteome analysis.}, } @article {pmid30458705, year = {2018}, author = {Van Renne, N and Wei, R and Pochet, N and Nauwynck, HJ}, title = {Dissecting clinical outcome of porcine circovirus type 2 with in vivo derived transcriptomic signatures of host tissue responses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {831}, pmid = {30458705}, issn = {1471-2164}, support = {201406300044//China Scholarship Council (CN)/ ; }, abstract = {BACKGROUND: Porcine Circovirus Type 2 (PCV2) is a pathogen that has the ability to cause often devastating disease manifestations in pig populations with major economic implications. How PCV2 establishes subclinical persistence and why certain individuals progress to lethal lymphoid depletion remain to be elucidated.

RESULTS: Here we present PorSignDB, a gene signature database describing in vivo porcine tissue physiology that we generated from a large compendium of in vivo transcriptional profiles and that we subsequently leveraged for deciphering the distinct physiological states underlying PCV2-affected lymph nodes. This systems genomics approach indicated that subclinical PCV2 infections suppress a myeloid leukocyte mediated immune response. However, in contrast an inflammatory myeloid cell activation is promoted in PCV2 patients with clinical manifestations. Functional genomics further uncovered STAT3 as a druggable PCV2 host factor candidate. Moreover, IL-2 supplementation of primary lymphocytes enabled ex vivo study of PCV2 replication in its target cell, the lymphoblast.

CONCLUSION: Our systematic dissection of the mechanistic basis of PCV2 reveals that subclinical and clinical PCV2 display two diametrically opposed immunotranscriptomic recalibrations that represent distinct physiological states in vivo, which suggests a paradigm shift in this field. Finally, our PorSignDB signature database is publicly available as a community resource (http://www.vetvirology.ugent.be/PorSignDB/ , included in Gene Sets from Community Contributors http://software.broadinstitute.org/gsea/msigdb/contributed_genesets.jsp) and provides systems biologists with a valuable tool for catalyzing studies of human and veterinary disease. Finally, a primary porcine lymphoblast cell culture system paves the way for unraveling the impact of host genetics on PCV2 replication.}, } @article {pmid30458702, year = {2018}, author = {Li, KL and Zhang, L and Yang, XM and Fang, Q and Yin, XF and Wei, HM and Zhou, T and Li, YB and Chen, XL and Tang, F and Li, YH and Chang, JF and Li, W and Sun, F}, title = {Histone acetyltransferase CBP-related H3K23 acetylation contributes to courtship learning in Drosophila.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {20}, pmid = {30458702}, issn = {1471-213X}, support = {31330043//National Natural Science Foundation of China Grants/ ; 31671528//National Natural Science Foundation of China Grants/ ; 2017YFA0103301//National Key R&D Program of China/ ; 2016YFA0100403//National Key R&D Program of China/ ; 2015CB856204//973 program of the Ministry of Science and Technology of China/ ; 2014CB964603//973 program of the Ministry of Science and Technology of China/ ; 2015CB964802//973 program of the Ministry of Science and Technology of China/ ; }, abstract = {BACKGROUND: Histone modifications are critical in regulating neuronal processes. However, the impacts of individual histone modifications on learning and memory are elusive. Here, we investigated the contributions of histone H3 lysine modifications to learning and memory in Drosophila by using histone lysine-to-alanine mutants.

RESULTS: Behavioural analysis indicated that compared to the H3WT group, mutants overexpressing H3K23A displayed impaired courtship learning. Chromatin immunoprecipitation analysis of H3K23A mutants showed that H3K23 acetylation (H3K23ac) levels were decreased on learning-related genes. Knockdown of CREB-binding protein (CBP) decreased H3K23ac levels, attenuated the expression of learning-related genes, led to a courtship learning defect and altered development of the mushroom bodies. A decline in courtship learning ability was observed in both larvae and adult treatments with ICG-001. Furthermore, treatment of Drosophila overexpressing mutated H3K23A with a CBP inhibitor did not aggravate the learning defect.

CONCLUSIONS: H3K23ac, catalysed by the acetyltransferases dCBP, contributes to Drosophila learning, likely by controlling the expression of specific genes. This is a novel epigenetic regulatory mechanism underlying neuronal behaviours.}, } @article {pmid30458701, year = {2018}, author = {Banos, S and Lentendu, G and Kopf, A and Wubet, T and Glöckner, FO and Reich, M}, title = {A comprehensive fungi-specific 18S rRNA gene sequence primer toolkit suited for diverse research issues and sequencing platforms.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {190}, pmid = {30458701}, issn = {1471-2180}, abstract = {BACKGROUND: Several fungi-specific primers target the 18S rRNA gene sequence, one of the prominent markers for fungal classification. The design of most primers goes back to the last decades. Since then, the number of sequences in public databases increased leading to the discovery of new fungal groups and changes in fungal taxonomy. However, no reevaluation of primers was carried out and relevant information on most primers is missing. With this study, we aimed to develop an 18S rRNA gene sequence primer toolkit allowing an easy selection of the best primer pair appropriate for different sequencing platforms, research aims (biodiversity assessment versus isolate classification) and target groups.

RESULTS: We performed an intensive literature research, reshuffled existing primers into new pairs, designed new Illumina-primers, and annealing blocking oligonucleotides. A final number of 439 primer pairs were subjected to in silico PCRs. Best primer pairs were selected and experimentally tested. The most promising primer pair with a small amplicon size, nu-SSU-1333-5'/nu-SSU-1647-3' (FF390/FR-1), was successful in describing fungal communities by Illumina sequencing. Results were confirmed by a simultaneous metagenomics and eukaryote-specific primer approach. Co-amplification occurred in all sample types but was effectively reduced by blocking oligonucleotides.

CONCLUSIONS: The compiled data revealed the presence of an enormous diversity of fungal 18S rRNA gene primer pairs in terms of fungal coverage, phylum spectrum and co-amplification. Therefore, the primer pair has to be carefully selected to fulfill the requirements of the individual research projects. The presented primer toolkit offers comprehensive lists of 164 primers, 439 primer combinations, 4 blocking oligonucleotides, and top primer pairs holding all relevant information including primer's characteristics and performance to facilitate primer pair selection.}, } @article {pmid30458649, year = {2018}, author = {Robertson, JM and Kingsley, BE}, title = {Sexually Dimorphic Faciometrics in Black Racial Groups From Early Adulthood to Late Middle Age.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918811056}, doi = {10.1177/1474704918811056}, pmid = {30458649}, issn = {1474-7049}, abstract = {An increasing body of research focusing on gender-related traits has utilized faciometrics in order to consider sexual dimorphism: Aspects as diverse as social heuristics, facial attractiveness, sexual orientation, aggression, and trustworthiness have all been investigated. However, the majority of these studies have tended to focus on White or Caucasian student populations and have paid little regard to either older populations or racial background. The current study therefore investigated sexual dimorphism in 450 participants (225 women) from a Black population across four age groups (20s, 30s, 40s, and 50s). In line with much previous research using White or Caucasian faces, the expected sexual dimorphism was seen in the younger age-group in three of the four indices (cheekbone prominence, facial width to lower facial height, and lower face height to full face height). However, consistent with more recent literature, the facial width to height ratio (fWHR) was not found to be significantly different between men and women in this age-group. Contrary to previous research, when considering broader age groups, the three established measures of facial sexual dimorphism, when looked at independently, remained static over time, but this was not true for fWHR. It is concluded that facial structure does not follow the same aging trajectory in all populations and care should be taken in choice of facial metric, depending on the nature of the sample under investigation.}, } @article {pmid30458171, year = {2019}, author = {Dolan, CP and Yan, M and Zimmel, K and Yang, TJ and Leininger, E and Dawson, LA and Muneoka, K}, title = {Axonal regrowth is impaired during digit tip regeneration in mice.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {237-244}, doi = {10.1016/j.ydbio.2018.11.010}, pmid = {30458171}, issn = {1095-564X}, abstract = {Mice are intrinsically capable of regenerating the tips of their digits after amputation. Mouse digit tip regeneration is reported to be a peripheral nerve-dependent event. However, it is presently unknown what types of nerves and Schwann cells innervate the digit tip, and to what extent these cells regenerate in association with the regenerative response. Given the necessity of peripheral nerves for mammalian regeneration, we investigated the neuroanatomy of the unamputated, regenerating, and regenerated mouse digit tip. Using immunohistochemistry for β-III-tubulin (β3T) or neurofilament H (NFH), substance P (SP), tyrosine hydroxylase (TH), myelin protein zero (P0), and glial fibrillary acidic protein (GFAP), we identified peripheral nerve axons (sensory and sympathetic), and myelinating- and non-myelinating-Schwann cells. Our findings show that the digit tip is innervated by two digital nerves that each bifurcate into a bone marrow (BM) and connective tissue (CT) branch. The BM branches are composed of sympathetic axons that are ensheathed by non-myelinating-Schwann cells whereas the CT branches are composed of sensory and sympathetic axons and are ensheathed by myelinating- and non-myelinating-Schwann cells. The regenerated digit neuroanatomy differs from unamputated digit in several key ways. First, there is 7.5 fold decrease in CT branch axons in the regenerated digit compared to the unampuated digit. Second, there is a 5.6 fold decrease in myelinating-Schwann cells in the regenerated digit compared to the unamputated digit that is consistent with the decrease in CT branch axons. Importantly, we also find that the central portion of the regenerating digit blastema is aneural, with axons and Schwann cells restricted to peripheral and distal blastema regions. Finally, we show that even with impaired innervation, digits maintain the ability to regenerate after re-amputation. Taken together, these data indicate that nerve regeneration is impaired in the context of mouse digit tip regeneration.}, } @article {pmid30458170, year = {2018}, author = {Lu, Q and Bhattachan, P and Dong, B}, title = {Ascidian notochord elongation.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.11.009}, pmid = {30458170}, issn = {1095-564X}, abstract = {The elongation of embryo and tissue is a key morphogenetic event in embryogenesis and organogenesis. Notochord, a typical chordate organ, undergoes elongation to perform its regulatory roles and to form the structural support in the embryo. Notochord elongation is morphologically similar across all chordates, but ascidian has evolved distinct molecular and cellular processes. Here, we summarize the current understanding of ascidian notochord elongation. We divide the process into three phases and discuss the underlying molecular mechanisms in each phase. In the first phase, the notochord converges and extends through invagination and mediolateral intercalation, and partially elongates to form a single diameter cell column along the anterior-posterior axis. In the second phase, a cytokinesis-like actomyosin ring is constructed at the equator of each cell and drives notochord to elongate approximately two-fold. The molecular composition and architecture of the ascidian notochord contractile ring are similar to that of the cytokinetic ring. However, the notochord contractile ring does not impose cell division but only drives cell elongation followed by disassembly. We discuss the self-organizing property of the circumferential actomyosin ring, and why it disassembles when certain notochord length is achieved. The similar ring structures are also present in the elongation process of other organs in evolutionarily divergent animals such as Drosophila and C. elegans. We hereby propose that actomyosin ring-based circumferential contraction is a common mechanism adopted in diverse systems to drive embryo and tissue elongation. In the third phase, the notochord experiences tubulogenesis and the endothelial-like cells crawl bi-directionally on the notochord sheath to further lengthen the notochord. In this review, we also discuss extracellular matrix proteins, notochord sheath, and surrounding tissues that may contribute to notochord integrity and morphogenesis.}, } @article {pmid30457516, year = {2019}, author = {De Meyer, SE and Andrews, M and James, EK and Willems, A}, title = {Mesorhizobium carmichaelinearum sp. nov., isolated from Carmichaelineae spp. root nodules.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {146-152}, doi = {10.1099/ijsem.0.003120}, pmid = {30457516}, issn = {1466-5034}, abstract = {Five strains of Gram-stain-negative, rod-shaped bacteria were isolated from Carmichaelia and Montigena root nodules. Based on 16S rRNA gene phylogeny, they were shown to belong to the genus Mesorhizobium, and to be most closely related to Mesorhizobium jarvisii ATCC 33669T (100-99.6 % sequence similarity), Mesorhizobium huakuii IAM 14158T (99.9-99.6 %), Mesorhizobium japonicum MAFF303099T (99.8-99.6 %) and Mesorhizobium erdmanii USDA 3471T (99.8-99.5 %). Additionally, the strains formed distinct groups based on housekeeping gene analysis and were most closely related to M. jarvisii ATCC 33669T (89.6-89.5 and 97.6-97.3 % sequence similarity for glnII and recA, respectively), M. erdmanii USDA 3471T (94.3-94.0 and 94.9-94.1 %), M. japonicum MAFF303099T (90.0-89.9 and 96.7-96.2 %) and M. huakuii IAM 14158T (89.9-90.0 and 95.4-94.9 %). Chemotaxonomic data supported the assignment of the strains to the genus Mesorhizobium and DNA-DNA hybridizations, average nucleotide identity analysis, matrix-assisted laser desorption ionization time-of-flight MS analysis, physiological and biochemical tests differentiated them genotypically and phenotypically from their nearest neighbouring species. Therefore, these strains are considered to represent a novel species, for which the name Mesorhizobium carmichaelinearum sp. nov. is proposed. The type strain is ICMP 18942T (=MonP1N1T=LMG 28414T).}, } @article {pmid30457514, year = {2019}, author = {Kim, JH and Kanjanasuntree, R and Kim, DH and Lee, JS and Sukhoom, A and Kantachote, D and Kim, W}, title = {Arenibacillus arenosus gen. nov., sp. nov., a member of the family Rhodobacteraceae isolated from sea sand.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {153-158}, doi = {10.1099/ijsem.0.003121}, pmid = {30457514}, issn = {1466-5034}, abstract = {A Gram-stain-negative, aerobic, non-motile, non-spore-forming, rod-shaped bacterial strain, designated CAU 1304T, was isolated from sea sand. Strain CAU 1304T grew optimally at pH 8.5 and 30 °C and in the presence of 1 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CAU 1304T belonged to the family Rhodobacteraceae, and was most closely related to Roseicitreum antarcticum ZS2-28T (96.54 % similarity) and Rhodobacter veldkampii ATCC 35703T (96.46 %). The major fatty acid was C18 : 1ω7c and the respiratory quinone was Q-10. The polar lipids were composed of phosphatidylglycerol, phosphatidylcholine and an unidentified aminolipid. The DNA G+C content was 55.9 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analysis, it is proposed that strain CAU 1304T represents a novel species of a new genus of the family Rhodobacteraceae, for which the name Arenibacillus arenosus gen. nov., sp. nov. is proposed. The type strain of Arenibacillus arenosus is CAU 1304T (=KCTC 42827T=NBRC 113022T).}, } @article {pmid30457513, year = {2019}, author = {Wang, XT and Han, JR and Zheng, WS and Zhang, XK and Du, ZJ}, title = {Aliidiomarina celeris sp. nov., isolated from coastal sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {171-176}, doi = {10.1099/ijsem.0.003123}, pmid = {30457513}, issn = {1466-5034}, abstract = {A Gram-stain-negative, heterotrophic, facultative anaerobic, gliding and motile bacterium, approximately 0.6-0.9 µm wide and 1.5-2.6 µm long, designated F3105T, was isolated from a marine sediment sample collected along the coast of Rongcheng, China . The growth of strain F3105T occurred on media with 1.0-8.0 % (w/v) NaCl (optimum, 2.0-3.0 %) and a pH of 6.5-9.5 (optimum, pH 7.5) at 4-45 °C (optimum, 37 °C). The phylogenetic analysis of the 16S rRNA gene and chemotaxonomic data revealed that the isolate belonged to the genus Aliidiomarina, and is closely related to Aliidiomarina shirensis (95.9 % sequence similarity). The sole isoprenoid quinone was Q-8. The major cellular fatty acids of the isolate were iso-C15 : 0, iso-C17 : 1ω9c and iso-C17 : 0, and its polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminolipid, two unidentified lipids and two unidentified aminophospholipids. The DNA G+C content of strain F3105T was 49.5 mol%. On the basis of phenotypic distinctiveness and phylogenetic divergence, strain F3105T is considered to represent a novel species of the genus Aliidiomarina, for which the name Aliidiomarinaceleris sp. nov. is proposed. The type strain is F3105T (=MCCC 1H00223T=KCTC 52891T).}, } @article {pmid30457512, year = {2018}, author = {Timilsina, S and Kara, S and Jacques, MA and Potnis, N and Minsavage, GV and Vallad, GE and Jones, JB and Fischer-Le Saux, M}, title = {Reclassification of Xanthomonas gardneri (ex Šutič 1957) Jones et al. 2006 as a later heterotypic synonym of Xanthomonas cynarae Trébaol et al. 2000 and description of X. cynarae pv. cynarae and X. cynarae pv. gardneri based on whole genome analyses.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003104}, pmid = {30457512}, issn = {1466-5034}, abstract = {Multilocus sequence analysis of Xanthomonas species revealed a very close relationship between Xanthomonas cynarae, an artichoke pathogen and Xanthomonas gardneri, a tomato and pepper pathogen. Results of whole genome sequence comparisons using average nucleotide identity between representative strains of X. gardneri and X. cynarae were well above the threshold of 95-96 %. Inoculations of X. gardneri strains in artichoke leaves caused mild disease symptoms, but only weak symptoms were observed in the bracts. Both X. cynarae and X. gardneri grew equally and caused typical bacterial spot symptoms in pepper after artificial inoculation. However, X. cynarae induced a hypersensitive reaction in tomato, while X. gardneri strains were virulent. Pathogenicity-associated gene clusters, including the protein secretion systems, type III effector profiles, and lipopolysaccharide cluster were nearly identical between the two species. Based on our results from whole genome sequence comparison, X. gardneri and X. cynarae belong to the same species. The name X. cynarae has priority and X. gardneri should be considered as a later heterotypic synonym. An emended description of X. cynarae (type strain=CFBP 4188T, =DSM 16794T) is given. However, due to the host specificity in artichoke and tomato, two pathovars, X. cynarae pv. cynarae and X. cynarae pv. gardneri, are proposed.}, } @article {pmid30457511, year = {2019}, author = {Leclercq, A and Moura, A and Vales, G and Tessaud-Rita, N and Aguilhon, C and Lecuit, M}, title = {Listeria thailandensis sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {74-81}, doi = {10.1099/ijsem.0.003097}, pmid = {30457511}, issn = {1466-5034}, abstract = {During a screening of Listeria species in food samples in Thailand, a Listeria-like bacterium was recovered from fried chicken and could not be assigned to any known species. Phylogenetic analysis based on the 16S rRNA gene and on 243 Listeria core genes placed the novel taxon within the Listeria aquatica, Listeria floridensis, Listeria fleishmannii and Listeria costaricensis clade (Listeria sensu lato), with highest similarity to L. floridensis (98.9 %) and L. costaricensis (98.8 %). Whole-genome sequence analyses based on the average nucleotide blast identity (ANI<86 %), the pairwise amino acid identity (AAI>64 %) and on the percentage of conserved proteins (POCP>77 %) with currently known Listeria species confirmed that the strain constituted a new taxon within the genus Listeria. At the phenotypical level, it differs from other Listeria species by the production of acid from d-tagatose and inositol. The name Listeria thailandensis sp. nov. is proposed for the novel species, and is represented by the type strain CLIP 2015/00305T (=CIP 111635T=DSM 107638T).}, } @article {pmid30457510, year = {2019}, author = {Phurbu, D and Lu, H and Xue, X and Tian, Y and Pema, Y and Ma, C and Xing, P}, title = {Flavobacterium tibetense sp. nov., isolated from a wetland.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {165-170}, doi = {10.1099/ijsem.0.003124}, pmid = {30457510}, issn = {1466-5034}, abstract = {A novel, Gram-stain-negative, non-motile and rod-shaped bacterium, designated YH5T, was isolated from the YonghuCo wetland on the Tibetan Plateau. The strain was able to grow optimally with 1 % (w/v) NaCl and tolerated up to 3 % NaCl. Growth occurred at pH 6-9 (optimum pH 7) and 10-37 °C (optimum 30 °C). Vitamins were not required for growth. The major polar lipid of strain YH5T was phosphatidylethanolamine. The predominant respiratory quinone was menaquinone 6 (MK-6). The major fatty acids were iso-C15 : 0, C16 : 0 10-methyl and/or iso-C17 : 1ω9c, iso-C17 : 0 3-OH, iso-C15 : 1 G and iso-C15 : 0 3-OH. Genome sequencing revealed a genome size of 2.74 Mbp and a G+C content of 33.3 mol%. Analysis of 16S rRNA gene sequences showed that strain YH5T belonged to the genus Flavobacterium, with the closest neighbours Flavobacterium luticocti xz20T (96.7 % similarity), Flavobacterium jejuense EC11T (96.4 %), Flavobacterium jumunjinense HME7102T (95.9 %) and Flavobacterium dongtanense LW30T (95.6 %). DNA-DNA relatedness between strain YH5T and the closest phylogenetically related strain F. luticocti xz20T was 27.0 %. Strain YH5T was clearly distinguished from the reference type strains based on phylogenetic analysis, DNA-DNA hybridization, fatty acid composition and a range of physiological and biochemical characteristics. Based on its phenotypic and chemotaxonomic characteristics, strain YH5T is classified as a representative of a novel species of the genus Flavobacterium, for which the name Flavobacterium tibetense sp. nov. is proposed. The type strain is YH5T (=CICC 24247T=KCTC 62174T).}, } @article {pmid30456442, year = {2018}, author = {Moros-Nicolás, C and Fouchécourt, S and Goudet, G and Monget, P}, title = {Genes Encoding Mammalian Oviductal Proteins Involved in Fertilization are Subjected to Gene Death and Positive Selection.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {655-667}, pmid = {30456442}, issn = {1432-1432}, support = {European Union's Horizon 2020 Research and Innovation Programme under grant agreement No. 677353//Horizon 2020 Framework Programme/ ; }, abstract = {Oviductal proteins play an important role in mammalian fertilization, as proteins from seminal fluid. However, in contrast with the latter, their phylogenetic evolution has been poorly studied. Our objective was to study in 16 mammals the evolution of 16 genes that encode oviductal proteins involved in at least one of the following steps: (1) sperm-oviduct interaction, (2) acrosome reaction, and/or (3) sperm-zona pellucida interaction. Most genes were present in all studied mammals. However, some genes were lost along the evolution of mammals and found as pseudogenes: annexin A5 (ANXA5) and deleted in malignant brain tumor 1 (DMBT1) in tarsier; oviductin (OVGP1) in megabat; and probably progestagen-associated endometrial protein (PAEP) in tarsier, mouse, rat, rabbit, dolphin, and megabat; prostaglandin D2 synthase (PTGDS) in microbat; and plasminogen (PLG) in megabat. Four genes [ANXA1, ANXA4, ANXA5, and heat shock 70 kDa protein 5 (HSPA5)] showed branch-site positive selection, whereas for seven genes [ANXA2, lactotransferrin (LTF), OVGP1, PLG, S100 calcium-binding protein A11 (S100A11), Sperm adhesion molecule 1 (SPAM1), and osteopontin (SPP1)] branch-site model and model-site positive selection were observed. These results strongly suggest that genes encoding oviductal proteins that are known to be important for gamete fertilization are subjected to positive selection during evolution, as numerous genes encoding proteins from mammalian seminal fluid. This suggests that such a rapid evolution may have as a consequence that two isolated populations become separate species more rapidly.}, } @article {pmid30456441, year = {2019}, author = {Serrano-Solís, V and Toscano Soares, PE and de Farías, ST}, title = {Genomic Signatures Among Acanthamoeba polyphaga Entoorganisms Unveil Evidence of Coevolution.}, journal = {Journal of molecular evolution}, volume = {87}, number = {1}, pages = {7-15}, doi = {10.1007/s00239-018-9877-1}, pmid = {30456441}, issn = {1432-1432}, abstract = {The definition of a genomic signature (GS) is "the total net response to selective pressure". Recent isolation and sequencing of naturally occurring organisms, hereby named entoorganisms, within Acanthamoeba polyphaga, raised the hypothesis of a common genomic signature despite their diverse and unrelated evolutionary origin. Widely accepted and implemented tests for GS detection are oligonucleotide relative frequencies (OnRF) and relative codon usage (RCU) surveys. A common pattern and strong correlations were unveiled from OnRFs among A. polyphaga's Mimivirus and virophage Sputnik. RCU showed a common A-T bias at third codon position. We expanded tests to the amoebal mitochondrial genome and amoeba-resistant bacteria, achieving strikingly coherent results to the aforementioned viral analyses. The GSs in these entoorganisms of diverse evolutionary origin are coevolutionarily conserved within an intracellular environment that provides sanctuary for species of ecological and biomedical relevance.}, } @article {pmid30456440, year = {2018}, author = {Runnels, CM and Lanier, KA and Williams, JK and Bowman, JC and Petrov, AS and Hud, NV and Williams, LD}, title = {Folding, Assembly, and Persistence: The Essential Nature and Origins of Biopolymers.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {598-610}, pmid = {30456440}, issn = {1432-1432}, support = {NNX16AJ28G and NNX16AJ29G//National Aeronautics and Space Administration (US)/ ; }, abstract = {Life as we know it requires three basic types of polymers: polypeptide, polynucleotide, and polysaccharide. Here we evaluate both universal and idiosyncratic characteristics of these biopolymers. We incorporate this information into a model that explains much about their origins, selection, and early evolution. We observe that all three biopolymer types are pre-organized, conditionally self-complementary, chemically unstable in aqueous media yet persistent because of kinetic trapping, with chiral monomers and directional chains. All three biopolymers are synthesized by dehydration reactions that are catalyzed by molecular motors driven by hydrolysis of phosphorylated nucleosides. All three biopolymers can access specific states that protect against hydrolysis. These protected states are folded, using self-complementary interactions among recurrent folding elements within a given biopolymer, or assembled, in associations between the same or different biopolymer types. Self-association in a hydrolytic environment achieves self-preservation. Heterogeneous association achieves partner-preservation. These universal properties support a model in which life's polymers emerged simultaneously and co-evolved in a common hydrolytic milieu where molecular persistence depended on folding and assembly. We believe that an understanding of the structure, function, and origins of any given type of biopolymer requires the context of other biopolymers.}, } @article {pmid30455951, year = {2018}, author = {Fedson, DS}, title = {Influenza, evolution, and the next pandemic.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {260-269}, pmid = {30455951}, issn = {2050-6201}, abstract = {Mortality rates in influenza appear to have been shaped by evolution. During the 1918 pandemic, mortality rates were lower in children compared with adults. This mortality difference occurs in a wide variety of infectious diseases. It has been replicated in mice and might be due to greater tolerance of infection, not greater resistance. Importantly, combination treatment with inexpensive and widely available generic drugs (e.g. statins and angiotensin receptor blockers) might change the damaging host response in adults to a more tolerant response in children. These drugs might work by modifying endothelial dysfunction, mitochondrial biogenesis and immunometabolism. Treating the host response might be the only practical way to reduce global mortality during the next influenza pandemic. It might also help reduce mortality due to seasonal influenza and other forms of acute critical illness. To realize these benefits, we need laboratory and clinical studies of host response treatment before and after puberty.}, } @article {pmid30455950, year = {2018}, author = {Rezzoagli, C and Wilson, D and Weigert, M and Wyder, S and Kümmerli, R}, title = {Probing the evolutionary robustness of two repurposed drugs targeting iron uptake in Pseudomonas aeruginosa.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {246-259}, pmid = {30455950}, issn = {2050-6201}, abstract = {Lay Summary: We probed the evolutionary robustness of two antivirulence drugs, gallium and flucytosine, targeting the iron-scavenging pyoverdine in the opportunistic pathogen Pseudomonas aeruginosa. Using an experimental evolution approach in human serum, we showed that antivirulence treatments are not evolutionarily robust per se, but vary in their propensity to select for resistance.

Background and objectives: Treatments that inhibit the expression or functioning of bacterial virulence factors hold great promise to be both effective and exert weaker selection for resistance than conventional antibiotics. However, the evolutionary robustness argument, based on the idea that antivirulence treatments disarm rather than kill pathogens, is controversial. Here, we probe the evolutionary robustness of two repurposed drugs, gallium and flucytosine, targeting the iron-scavenging pyoverdine of the opportunistic human pathogen Pseudomonas aeruginosa.

Methodology: We subjected replicated cultures of bacteria to two concentrations of each drug for 20 consecutive days in human serum as an ex vivo infection model. We screened evolved populations and clones for resistance phenotypes, including the restoration of growth and pyoverdine production, and the evolution of iron uptake by-passing mechanisms. We whole-genome sequenced evolved clones to identify the genetic basis of resistance.

Results: We found that mutants resistant against antivirulence treatments readily arose, but their selective spreading varied between treatments. Flucytosine resistance quickly spread in all populations due to disruptive mutations in upp, a gene encoding an enzyme required for flucytosine activation. Conversely, resistance against gallium arose only sporadically, and was based on mutations in transcriptional regulators, upregulating pyocyanin production, a redox-active molecule promoting siderophore-independent iron acquisition. The spread of gallium resistance was presumably hampered because pyocyanin-mediated iron delivery benefits resistant and susceptible cells alike.

Conclusions and implications: Our work highlights that antivirulence treatments are not evolutionarily robust per se. Instead, evolutionary robustness is a relative measure, with specific treatments occupying different positions on a continuous scale.}, } @article {pmid30455841, year = {2018}, author = {Jung, JH and Joe, MH and Kim, DH and Park, H and Choi, JI and Lim, S}, title = {Complete genome sequence of Planococcus sp. PAMC21323 isolated from Antarctica and its metabolic potential to detoxify pollutants.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {31}, pmid = {30455841}, issn = {1944-3277}, abstract = {The Planococcus sp. PAMC21323 is a yellow pigment-producing bacterium isolated from King George Island in Antarctica; it has a broad growth temperature range of 5-40 °C. Herein, we describe the complete genome sequence information of the genus Planococcus with its annotated sequence, genetic features for bioremediation, and oxidative stress capacity. The Planococcus sp. PAMC21323 possesses chromosomal DNA (3,196,500-bp) with plasmid DNA (3364-bp). The complete 3,199,864-bp of the genome consists of 3171 genes including 60 transfer RNAs and 24 ribosomal RNAs. Strain PAMC21323 encodes various genes associated with detoxification of heavy metal ions and aromatic hydrocarbons. Moreover, it is equipped with diverse stress response systems, which can be used to sense the internal and oxidative stresses caused by detoxification. This is the first report highlighting the genetic potential of Planococcus sp. PAMC21323 in bioremediation, suggesting application of this psychrotrophic strain in bioremediation in harsh environments.}, } @article {pmid30455472, year = {2019}, author = {Fujiwara, S and Hoshizaki, M and Ichida, Y and Lex, D and Kuroda, E and Ishii, KJ and Magi, S and Okada, M and Takao, H and Gandou, M and Imai, H and Hara, R and Herzog, H and Yoshimura, A and Okamura, H and Penninger, JM and Slutsky, AS and Uhlig, S and Kuba, K and Imai, Y}, title = {Pulmonary phagocyte-derived NPY controls the pathology of severe influenza virus infection.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {258-268}, doi = {10.1038/s41564-018-0289-1}, pmid = {30455472}, issn = {2058-5276}, abstract = {Crosstalk between the autonomic nervous system and the immune system by means of the sympathetic and parasympathetic pathways is a critical process in host defence. Activation of the sympathetic nervous system results in the release of catecholamines as well as neuropeptide Y (NPY). Here, we investigated whether phagocytes are capable of the de novo production of NPY, as has been described for catecholamines. We show that the synthesis of NPY and its Y1 receptor (Y1R) is increased in phagocytes in lungs following severe influenza virus infection. The genetic deletion of Npy or Y1r specifically in phagocytes greatly improves the pathology of severe influenza virus infection, which is characterized by excessive virus replication and pulmonary inflammation. Mechanistically, it is the induction of suppressor of cytokine signalling 3 (SOCS3) via NPY-Y1R activation that is responsible for impaired antiviral response and promoting pro-inflammatory cytokine production, thereby enhancing the pathology of influenza virus infection. Thus, direct regulation of the NPY-Y1R-SOCS3 pathway on phagocytes may act as a fine-tuner of an innate immune response to virus infection, which could be a therapeutic target for lethal influenza virus infection.}, } @article {pmid30455471, year = {2019}, author = {Goo, L and Debbink, K and Kose, N and Sapparapu, G and Doyle, MP and Wessel, AW and Richner, JM and Burgomaster, KE and Larman, BC and Dowd, KA and Diamond, MS and Crowe, JE and Pierson, TC}, title = {A protective human monoclonal antibody targeting the West Nile virus E protein preferentially recognizes mature virions.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {71-77}, doi = {10.1038/s41564-018-0283-7}, pmid = {30455471}, issn = {2058-5276}, support = {T32 AI112541/AI/NIAID NIH HHS/United States ; }, abstract = {West Nile virus (WNV), a member of the Flavivirus genus, is a leading cause of viral encephalitis in the United States1. The development of neutralizing antibodies against the flavivirus envelope (E) protein is critical for immunity and vaccine protection2. Previously identified candidate therapeutic mouse and human neutralizing monoclonal antibodies (mAbs) target epitopes within the E domain III lateral ridge and the domain I-II hinge region, respectively3. To explore the neutralizing antibody repertoire elicited by WNV infection for potential therapeutic application, we isolated ten mAbs from WNV-infected individuals. mAb WNV-86 neutralized WNV with a 50% inhibitory concentration of 2 ng ml-1, one of the most potently neutralizing flavivirus-specific antibodies ever isolated. WNV-86 targets an epitope in E domain II, and preferentially recognizes mature virions lacking an uncleaved form of the chaperone protein prM, unlike most flavivirus-specific antibodies4. In vitro selection experiments revealed a neutralization escape mechanism involving a glycan addition to E domain II. Finally, a single dose of WNV-86 administered two days post-infection protected mice from lethal WNV challenge. This study identifies a highly potent human neutralizing mAb with therapeutic potential that targets an epitope preferentially displayed on mature virions.}, } @article {pmid30455470, year = {2019}, author = {Kim, AS and Austin, SK and Gardner, CL and Zuiani, A and Reed, DS and Trobaugh, DW and Sun, C and Basore, K and Williamson, LE and Crowe, JE and Slifka, MK and Fremont, DH and Klimstra, WB and Diamond, MS}, title = {Protective antibodies against Eastern equine encephalitis virus bind to epitopes in domains A and B of the E2 glycoprotein.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {187-197}, pmid = {30455470}, issn = {2058-5276}, support = {R01 AI095436/AI/NIAID NIH HHS/United States ; }, abstract = {Eastern equine encephalitis virus (EEEV) is a mosquito-transmitted alphavirus with a high case mortality rate in humans. EEEV is a biodefence concern because of its potential for aerosol spread and the lack of existing countermeasures. Here, we identify a panel of 18 neutralizing murine monoclonal antibodies (mAbs) against the EEEV E2 glycoprotein, several of which have 'elite' activity with 50 and 99% effective inhibitory concentrations (EC50 and EC99) of less than 10 and 100 ng ml-1, respectively. Alanine-scanning mutagenesis and neutralization escape mapping analysis revealed epitopes for these mAbs in domains A or B of the E2 glycoprotein. A majority of the neutralizing mAbs blocked infection at a post-attachment stage, with several inhibiting viral membrane fusion. Administration of one dose of anti-EEEV mAb protected mice from lethal subcutaneous or aerosol challenge. These experiments define the mechanistic basis for neutralization by protective anti-EEEV mAbs and suggest a path forward for treatment and vaccine design.}, } @article {pmid30455469, year = {2019}, author = {Chittim, CL and Martínez Del Campo, A and Balskus, EP}, title = {Gut bacterial phospholipase Ds support disease-associated metabolism by generating choline.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {155-163}, doi = {10.1038/s41564-018-0294-4}, pmid = {30455469}, issn = {2058-5276}, abstract = {The essential nutrient choline is metabolized by gut bacteria to the disease-associated metabolite trimethylamine (TMA). However, most of the choline obtained via the diet and present in the human body is incorporated into larger metabolites, including the lipid phosphatidylcholine (PC). Here, we report that many choline-utilizing gut microorganisms can hydrolyse PC using a phospholipase D (PLD) enzyme and further convert the released choline to TMA. Genetic and in vitro characterization of the PLD from Escherichia coli MS 200-1 showed this enzyme is essential for bacterial hydrolysis of PC and prefers this substrate. PLDs are also found in gut bacterial isolates that are unable to convert choline to TMA, suggesting that additional members of the gut microbiota may influence access to this substrate. Unexpectedly, this PLD is only distantly related to characterized PLDs from pathogenic bacteria, suggesting a distinct evolutionary history. Together, these results reveal a previously underappreciated role for gut microorganisms in phospholipid metabolism and a potential target for inhibiting TMA production.}, } @article {pmid30455444, year = {2018}, author = {Malinsky, M and Svardal, H and Tyers, AM and Miska, EA and Genner, MJ and Turner, GF and Durbin, R}, title = {Whole-genome sequences of Malawi cichlids reveal multiple radiations interconnected by gene flow.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1940-1955}, doi = {10.1038/s41559-018-0717-x}, pmid = {30455444}, issn = {2397-334X}, abstract = {The hundreds of cichlid fish species in Lake Malawi constitute the most extensive recent vertebrate adaptive radiation. Here we characterize its genomic diversity by sequencing 134 individuals covering 73 species across all major lineages. The average sequence divergence between species pairs is only 0.1-0.25%. These divergence values overlap diversity within species, with 82% of heterozygosity shared between species. Phylogenetic analyses suggest that diversification initially proceeded by serial branching from a generalist Astatotilapia-like ancestor. However, no single species tree adequately represents all species relationships, with evidence for substantial gene flow at multiple times. Common signatures of selection on visual and oxygen transport genes shared by distantly related deep-water species point to both adaptive introgression and independent selection. These findings enhance our understanding of genomic processes underlying rapid species diversification, and provide a platform for future genetic analysis of the Malawi radiation.}, } @article {pmid30455443, year = {2018}, author = {Damschen, EI}, title = {Decoding plant communities across scales.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1844-1845}, doi = {10.1038/s41559-018-0739-4}, pmid = {30455443}, issn = {2397-334X}, } @article {pmid30455442, year = {2018}, author = {Doughty, CE and Santos-Andrade, PE and Shenkin, A and Goldsmith, GR and Bentley, LP and Blonder, B and Díaz, S and Salinas, N and Enquist, BJ and Martin, RE and Asner, GP and Malhi, Y}, title = {Tropical forest leaves may darken in response to climate change.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1918-1924}, doi = {10.1038/s41559-018-0716-y}, pmid = {30455442}, issn = {2397-334X}, support = {NE/J023418/1//Natural Environment Research Council (NERC)/ ; }, abstract = {Tropical forest leaf albedo (reflectance) greatly impacts how much energy the planet absorbs; however; little is known about how it might be impacted by climate change. Here, we measure leaf traits and leaf albedo at ten 1-ha plots along a 3,200-m elevation gradient in Peru. Leaf mass per area (LMA) decreased with warmer temperatures along the elevation gradient; the distribution of LMA was positively skewed at all sites indicating a shift in LMA towards a warmer climate and future reduced tropical LMA. Reduced LMA was significantly (P < 0.0001) correlated with reduced leaf near-infrared (NIR) albedo; community-weighted mean NIR albedo significantly (P < 0.01) decreased as temperature increased. A potential future 2 °C increase in tropical temperatures could reduce lowland tropical leaf LMA by 6-7 g m-2 (5-6%) and reduce leaf NIR albedo by 0.0015-0.002 units. Reduced NIR albedo means that leaves are darker and absorb more of the Sun's energy. Climate simulations indicate this increased absorbed energy will warm tropical forests more at high CO2 conditions with proportionately more energy going towards heating and less towards evapotranspiration and cloud formation.}, } @article {pmid30455441, year = {2019}, author = {Vullioud, C and Davidian, E and Wachter, B and Rousset, F and Courtiol, A and Höner, OP}, title = {Social support drives female dominance in the spotted hyaena.}, journal = {Nature ecology & evolution}, volume = {3}, number = {1}, pages = {71-76}, doi = {10.1038/s41559-018-0718-9}, pmid = {30455441}, issn = {2397-334X}, abstract = {Identifying how dominance within and between the sexes is established is pivotal to understanding sexual selection and sexual conflict. In many species, members of one sex dominate those of the other in one-on-one interactions. Whether this results from a disparity in intrinsic attributes, such as strength and aggressiveness, or in extrinsic factors, such as social support, is currently unknown. We assessed the effects of both mechanisms on dominance in the spotted hyaena (Crocuta crocuta), a species where sexual size dimorphism is low and females often dominate males. We found that individuals with greater potential social support dominated one-on-one interactions in all social contexts, irrespective of their body mass and sex. Female dominance emerged from a disparity in social support in favour of females. This disparity was a direct consequence of male-biased dispersal and the disruptive effect of dispersal on social bonds. Accordingly, the degree of female dominance varied with the demographic and kin structure of the social groups, ranging from male and female co-dominance to complete female dominance. Our study shows that social support can drive sex-biased dominance and provides empirical evidence that a sex-role-defining trait can emerge without the direct effect of sex.}, } @article {pmid30455440, year = {2018}, author = {Gogarty, B and Kirkpatrick, J and Fitzgerald, N and Jarman, S and McCormack, P and Marthick, J}, title = {Commercial tourism in Tasmania's wilderness threatens the attraction it exploits.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1826}, doi = {10.1038/s41559-018-0723-z}, pmid = {30455440}, issn = {2397-334X}, } @article {pmid30455439, year = {2018}, author = {Hiltunen, T and Cairns, J and Frickel, J and Jalasvuori, M and Laakso, J and Kaitala, V and Künzel, S and Karakoc, E and Becks, L}, title = {Dual-stressor selection alters eco-evolutionary dynamics in experimental communities.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1974-1981}, doi = {10.1038/s41559-018-0701-5}, pmid = {30455439}, issn = {2397-334X}, abstract = {Recognizing when and how rapid evolution drives ecological change is fundamental for our understanding of almost all ecological and evolutionary processes such as community assembly, genetic diversification and the stability of communities and ecosystems. Generally, rapid evolutionary change is driven through selection on genetic variation and is affected by evolutionary constraints, such as tradeoffs and pleiotropic effects, all contributing to the overall rate of evolutionary change. Each of these processes can be influenced by the presence of multiple environmental stressors reducing a population's reproductive output. Potential consequences of multistressor selection for the occurrence and strength of the link from rapid evolution to ecological change are unclear. However, understanding these is necessary for predicting when rapid evolution might drive ecological change. Here we investigate how the presence of two stressors affects this link using experimental evolution with the bacterium Pseudomonas fluorescens and its predator Tetrahymena thermophila. We show that the combination of predation and sublethal antibiotic concentrations delays the evolution of anti-predator defence and antibiotic resistance compared with the presence of only one of the two stressors. Rapid defence evolution drives stabilization of the predator-prey dynamics but this link between evolution and ecology is weaker in the two-stressor environment, where defence evolution is slower, leading to less stable population dynamics. Tracking the molecular evolution of whole populations over time shows further that mutations in different genes are favoured under multistressor selection. Overall, we show that selection by multiple stressors can significantly alter eco-evolutionary dynamics and their predictability.}, } @article {pmid30455438, year = {2018}, author = {Smith-Paredes, D and Núñez-León, D and Soto-Acuña, S and O'Connor, J and Botelho, JF and Vargas, AO}, title = {Dinosaur ossification centres in embryonic birds uncover developmental evolution of the skull.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1966-1973}, doi = {10.1038/s41559-018-0713-1}, pmid = {30455438}, issn = {2397-334X}, abstract = {Radical transformation of the skull characterizes bird evolution. An increase in the relative size of the brain and eyes was presumably related to the loss of two bones surrounding the eye, the prefrontal and postorbital. We report that ossification centres of the prefrontal and postorbital are still formed in bird embryos, which then fuse seamlessly to the developing nasal and frontal bones, respectively, becoming undetectable in the adult. The presence of a dinosaur-like ossification pattern in bird embryos is more than a trace of their evolutionary past: we show how persistent modularity of ossification centres has allowed for evolutionary re-organization of skull architecture in evolution. Our findings also demonstrate that enigmatic mesodermal cells forming the posterior region of the avian frontal correspond to the ossification centre of the postorbital, not the parietal, and link its failure to develop into an adult bone to its incorporation into the expanded braincase of birds.}, } @article {pmid30455437, year = {2018}, author = {Bruelheide, H and Dengler, J and Purschke, O and Lenoir, J and Jiménez-Alfaro, B and Hennekens, SM and Botta-Dukát, Z and Chytrý, M and Field, R and Jansen, F and Kattge, J and Pillar, VD and Schrodt, F and Mahecha, MD and Peet, RK and Sandel, B and van Bodegom, P and Altman, J and Alvarez-Dávila, E and Arfin Khan, MAS and Attorre, F and Aubin, I and Baraloto, C and Barroso, JG and Bauters, M and Bergmeier, E and Biurrun, I and Bjorkman, AD and Blonder, B and Čarni, A and Cayuela, L and Černý, T and Cornelissen, JHC and Craven, D and Dainese, M and Derroire, G and De Sanctis, M and Díaz, S and Doležal, J and Farfan-Rios, W and Feldpausch, TR and Fenton, NJ and Garnier, E and Guerin, GR and Gutiérrez, AG and Haider, S and Hattab, T and Henry, G and Hérault, B and Higuchi, P and Hölzel, N and Homeier, J and Jentsch, A and Jürgens, N and Kącki, Z and Karger, DN and Kessler, M and Kleyer, M and Knollová, I and Korolyuk, AY and Kühn, I and Laughlin, DC and Lens, F and Loos, J and Louault, F and Lyubenova, MI and Malhi, Y and Marcenò, C and Mencuccini, M and Müller, JV and Munzinger, J and Myers-Smith, IH and Neill, DA and Niinemets, Ü and Orwin, KH and Ozinga, WA and Penuelas, J and Pérez-Haase, A and Petřík, P and Phillips, OL and Pärtel, M and Reich, PB and Römermann, C and Rodrigues, AV and Sabatini, FM and Sardans, J and Schmidt, M and Seidler, G and Silva Espejo, JE and Silveira, M and Smyth, A and Sporbert, M and Svenning, JC and Tang, Z and Thomas, R and Tsiripidis, I and Vassilev, K and Violle, C and Virtanen, R and Weiher, E and Welk, E and Wesche, K and Winter, M and Wirth, C and Jandt, U}, title = {Global trait-environment relationships of plant communities.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1906-1917}, doi = {10.1038/s41559-018-0699-8}, pmid = {30455437}, issn = {2397-334X}, abstract = {Plant functional traits directly affect ecosystem functions. At the species level, trait combinations depend on trade-offs representing different ecological strategies, but at the community level trait combinations are expected to be decoupled from these trade-offs because different strategies can facilitate co-existence within communities. A key question is to what extent community-level trait composition is globally filtered and how well it is related to global versus local environmental drivers. Here, we perform a global, plot-level analysis of trait-environment relationships, using a database with more than 1.1 million vegetation plots and 26,632 plant species with trait information. Although we found a strong filtering of 17 functional traits, similar climate and soil conditions support communities differing greatly in mean trait values. The two main community trait axes that capture half of the global trait variation (plant stature and resource acquisitiveness) reflect the trade-offs at the species level but are weakly associated with climate and soil conditions at the global scale. Similarly, within-plot trait variation does not vary systematically with macro-environment. Our results indicate that, at fine spatial grain, macro-environmental drivers are much less important for functional trait composition than has been assumed from floristic analyses restricted to co-occurrence in large grid cells. Instead, trait combinations seem to be predominantly filtered by local-scale factors such as disturbance, fine-scale soil conditions, niche partitioning and biotic interactions.}, } @article {pmid30455424, year = {2018}, author = {Li, D and Xue, W and Li, M and Dong, M and Wang, J and Wang, X and Li, X and Chen, K and Zhang, W and Wu, S and Zhang, Y and Gao, L and Chen, Y and Chen, J and Zhou, BO and Zhou, Y and Yao, X and Li, L and Wu, D and Pan, W}, title = {VCAM-1+ macrophages guide the homing of HSPCs to a vascular niche.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {119-124}, doi = {10.1038/s41586-018-0709-7}, pmid = {30455424}, issn = {1476-4687}, support = {R35 HL135805/HL/NHLBI NIH HHS/United States ; }, abstract = {Haematopoietic stem and progenitor cells (HSPCs) give rise to all blood lineages that support the entire lifespan of vertebrates1. After HSPCs emerge from endothelial cells within the developing dorsal aorta, homing allows the nascent cells to anchor in their niches for further expansion and differentiation2-5. Unique niche microenvironments, composed of various blood vessels as units of microcirculation and other niche components such as stromal cells, regulate this process6-9. However, the detailed architecture of the microenvironment and the mechanism for the regulation of HSPC homing remain unclear. Here, using advanced live imaging and a cell-labelling system, we perform high-resolution analyses of the HSPC homing in caudal haematopoietic tissue of zebrafish (equivalent to the fetal liver in mammals), and reveal the role of the vascular architecture in the regulation of HSPC retention. We identify a VCAM-1+ macrophage-like niche cell population that patrols the inner surface of the venous plexus, interacts with HSPCs in an ITGA4-dependent manner, and directs HSPC retention. These cells, named 'usher cells', together with caudal venous capillaries and plexus, define retention hotspots within the homing microenvironment. Thus, the study provides insights into the mechanism of HSPC homing and reveals the essential role of a VCAM-1+ macrophage population with patrolling behaviour in HSPC retention.}, } @article {pmid30455423, year = {2019}, author = {Hu, Y and Marwick, B and Zhang, JF and Rui, X and Hou, YM and Yue, JP and Chen, WR and Huang, WW and Li, B}, title = {Late Middle Pleistocene Levallois stone-tool technology in southwest China.}, journal = {Nature}, volume = {565}, number = {7737}, pages = {82-85}, doi = {10.1038/s41586-018-0710-1}, pmid = {30455423}, issn = {1476-4687}, abstract = {Levallois approaches are one of the best known variants of prepared-core technologies, and are an important hallmark of stone technologies developed around 300,000 years ago in Africa and west Eurasia1,2. Existing archaeological evidence suggests that the stone technology of east Asian hominins lacked a Levallois component during the late Middle Pleistocene epoch and it is not until the Late Pleistocene (around 40,000-30,000 years ago) that this technology spread into east Asia in association with a dispersal of modern humans. Here we present evidence of Levallois technology from the lithic assemblage of the Guanyindong Cave site in southwest China, dated to approximately 170,000-80,000 years ago. To our knowledge, this is the earliest evidence of Levallois technology in east Asia. Our findings thus challenge the existing model of the origin and spread of Levallois technologies in east Asia and its links to a Late Pleistocene dispersal of modern humans.}, } @article {pmid30455422, year = {2018}, author = {Hoyt, JR and Langwig, KE and White, JP and Kaarakka, HM and Redell, JA and Kurta, A and DePue, JE and Scullon, WH and Parise, KL and Foster, JT and Frick, WF and Kilpatrick, AM}, title = {Cryptic connections illuminate pathogen transmission within community networks.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {710-713}, doi = {10.1038/s41586-018-0720-z}, pmid = {30455422}, issn = {1476-4687}, abstract = {Understanding host interactions that lead to pathogen transmission is fundamental to the prediction and control of epidemics1-5. Although the majority of transmissions often occurs within social groups6-9, the contribution of connections that bridge groups and species to pathogen dynamics is poorly understood10-12. These cryptic connections-which are often indirect or infrequent-provide transmission routes between otherwise disconnected individuals and may have a key role in large-scale outbreaks that span multiple populations or species. Here we quantify the importance of cryptic connections in disease dynamics by simultaneously characterizing social networks and tracing transmission dynamics of surrogate-pathogen epidemics through eight communities of bats. We then compared these data to the invasion of the fungal pathogen that causes white-nose syndrome, a recently emerged disease that is devastating North American bat populations13-15. We found that cryptic connections increased links between individuals and between species by an order of magnitude. Individuals were connected, on average, to less than two per cent of the population through direct contact and to only six per cent through shared groups. However, tracing surrogate-pathogen dynamics showed that each individual was connected to nearly fifteen per cent of the population, and revealed widespread transmission between solitarily roosting individuals as well as extensive contacts among species. Connections estimated from surrogate-pathogen epidemics, which include cryptic connections, explained three times as much variation in the transmission of the fungus that causes white-nose syndrome as did connections based on shared groups. These findings show how cryptic connections facilitate the community-wide spread of pathogens and can lead to explosive epidemics.}, } @article {pmid30455421, year = {2018}, author = {Bronselaer, B and Winton, M and Griffies, SM and Hurlin, WJ and Rodgers, KB and Sergienko, OV and Stouffer, RJ and Russell, JL}, title = {Change in future climate due to Antarctic meltwater.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {53-58}, doi = {10.1038/s41586-018-0712-z}, pmid = {30455421}, issn = {1476-4687}, support = {PLR-1425989//National Science Foundation/International ; OPP-1246151//National Science Foundation/International ; }, abstract = {Meltwater from the Antarctic Ice Sheet is projected to cause up to one metre of sea-level rise by 2100 under the highest greenhouse gas concentration trajectory (RCP8.5) considered by the Intergovernmental Panel on Climate Change (IPCC). However, the effects of meltwater from the ice sheets and ice shelves of Antarctica are not included in the widely used CMIP5 climate models, which introduces bias into IPCC climate projections. Here we assess a large ensemble simulation of the CMIP5 model 'GFDL ESM2M' that accounts for RCP8.5-projected Antarctic Ice Sheet meltwater. We find that, relative to the standard RCP8.5 scenario, accounting for meltwater delays the exceedance of the maximum global-mean atmospheric warming targets of 1.5 and 2 degrees Celsius by more than a decade, enhances drying of the Southern Hemisphere and reduces drying of the Northern Hemisphere, increases the formation of Antarctic sea ice (consistent with recent observations of increasing Antarctic sea-ice area) and warms the subsurface ocean around the Antarctic coast. Moreover, the meltwater-induced subsurface ocean warming could lead to further ice-sheet and ice-shelf melting through a positive feedback mechanism, highlighting the importance of including meltwater effects in simulations of future climate.}, } @article {pmid30455415, year = {2019}, author = {Gould, RA and Aziz, H and Woods, CE and Seman-Senderos, MA and Sparks, E and Preuss, C and Wünnemann, F and Bedja, D and Moats, CR and McClymont, SA and Rose, R and Sobreira, N and Ling, H and MacCarrick, G and Kumar, AA and Luyckx, I and Cannaerts, E and Verstraeten, A and Björk, HM and Lehsau, AC and Jaskula-Ranga, V and Lauridsen, H and Shah, AA and Bennett, CL and Ellinor, PT and Lin, H and Isselbacher, EM and Lino Cardenas, CL and Butcher, JT and Hughes, GC and Lindsay, ME and , and , and Mertens, L and Franco-Cereceda, A and Verhagen, JMA and Wessels, M and Mohamed, SA and Eriksson, P and Mital, S and Van Laer, L and Loeys, BL and Andelfinger, G and McCallion, AS and Dietz, HC}, title = {ROBO4 variants predispose individuals to bicuspid aortic valve and thoracic aortic aneurysm.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {42-50}, doi = {10.1038/s41588-018-0265-y}, pmid = {30455415}, issn = {1546-1718}, support = {//Howard Hughes Medical Institute/United States ; T32 GM007814/GM/NIGMS NIH HHS/United States ; U54 HG006542/HG/NHGRI NIH HHS/United States ; }, abstract = {Bicuspid aortic valve (BAV) is a common congenital heart defect (population incidence, 1-2%)1-3 that frequently presents with ascending aortic aneurysm (AscAA)4. BAV/AscAA shows autosomal dominant inheritance with incomplete penetrance and male predominance. Causative gene mutations (for example, NOTCH1, SMAD6) are known for ≤1% of nonsyndromic BAV cases with and without AscAA5-8, impeding mechanistic insight and development of therapeutic strategies. Here, we report the identification of variants in ROBO4 (which encodes a factor known to contribute to endothelial performance) that segregate with disease in two families. Targeted sequencing of ROBO4 showed enrichment for rare variants in BAV/AscAA probands compared with controls. Targeted silencing of ROBO4 or mutant ROBO4 expression in endothelial cell lines results in impaired barrier function and a synthetic repertoire suggestive of endothelial-to-mesenchymal transition. This is consistent with BAV/AscAA-associated findings in patients and in animal models deficient for ROBO4. These data identify a novel endothelial etiology for this common human disease phenotype.}, } @article {pmid30455414, year = {2019}, author = {Sherman, RM and Forman, J and Antonescu, V and Puiu, D and Daya, M and Rafaels, N and Boorgula, MP and Chavan, S and Vergara, C and Ortega, VE and Levin, AM and Eng, C and Yazdanbakhsh, M and Wilson, JG and Marrugo, J and Lange, LA and Williams, LK and Watson, H and Ware, LB and Olopade, CO and Olopade, O and Oliveira, RR and Ober, C and Nicolae, DL and Meyers, DA and Mayorga, A and Knight-Madden, J and Hartert, T and Hansel, NN and Foreman, MG and Ford, JG and Faruque, MU and Dunston, GM and Caraballo, L and Burchard, EG and Bleecker, ER and Araujo, MI and Herrera-Paz, EF and Campbell, M and Foster, C and Taub, MA and Beaty, TH and Ruczinski, I and Mathias, RA and Barnes, KC and Salzberg, SL}, title = {Assembly of a pan-genome from deep sequencing of 910 humans of African descent.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {30-35}, doi = {10.1038/s41588-018-0273-y}, pmid = {30455414}, issn = {1546-1718}, support = {R01 HG006677/HG/NHGRI NIH HHS/United States ; R01 HL104608/HL/NHLBI NIH HHS/United States ; R01 HL129239/HL/NHLBI NIH HHS/United States ; }, abstract = {We used a deeply sequenced dataset of 910 individuals, all of African descent, to construct a set of DNA sequences that is present in these individuals but missing from the reference human genome. We aligned 1.19 trillion reads from the 910 individuals to the reference genome (GRCh38), collected all reads that failed to align, and assembled these reads into contiguous sequences (contigs). We then compared all contigs to one another to identify a set of unique sequences representing regions of the African pan-genome missing from the reference genome. Our analysis revealed 296,485,284 bp in 125,715 distinct contigs present in the populations of African descent, demonstrating that the African pan-genome contains ~10% more DNA than the current human reference genome. Although the functional significance of nearly all of this sequence is unknown, 387 of the novel contigs fall within 315 distinct protein-coding genes, and the rest appear to be intergenic.}, } @article {pmid30455320, year = {2018}, author = {Smith, FD and Omar, MH and Nygren, PJ and Soughayer, J and Hoshi, N and Lau, HT and Snyder, CG and Branon, TC and Ghosh, D and Langeberg, LK and Ting, AY and Santana, LF and Ong, SE and Navedo, MF and Scott, JD}, title = {Single nucleotide polymorphisms alter kinase anchoring and the subcellular targeting of A-kinase anchoring proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11465-E11474}, doi = {10.1073/pnas.1816614115}, pmid = {30455320}, issn = {1091-6490}, support = {R01 DK105542/DK/NIDDK NIH HHS/United States ; R01 DK119192/DK/NIDDK NIH HHS/United States ; R01 HL098200/HL/NHLBI NIH HHS/United States ; R01 HL121059/HL/NHLBI NIH HHS/United States ; }, abstract = {A-kinase anchoring proteins (AKAPs) shape second-messenger signaling responses by constraining protein kinase A (PKA) at precise intracellular locations. A defining feature of AKAPs is a helical region that binds to regulatory subunits (RII) of PKA. Mining patient-derived databases has identified 42 nonsynonymous SNPs in the PKA-anchoring helices of five AKAPs. Solid-phase RII binding assays confirmed that 21 of these amino acid substitutions disrupt PKA anchoring. The most deleterious side-chain modifications are situated toward C-termini of AKAP helices. More extensive analysis was conducted on a valine-to-methionine variant in the PKA-anchoring helix of AKAP18. Molecular modeling indicates that additional density provided by methionine at position 282 in the AKAP18γ isoform deflects the pitch of the helical anchoring surface outward by 6.6°. Fluorescence polarization measurements show that this subtle topological change reduces RII-binding affinity 8.8-fold and impairs cAMP responsive potentiation of L-type Ca2+ currents in situ. Live-cell imaging of AKAP18γ V282M-GFP adducts led to the unexpected discovery that loss of PKA anchoring promotes nuclear accumulation of this polymorphic variant. Targeting proceeds via a mechanism whereby association with the PKA holoenzyme masks a polybasic nuclear localization signal on the anchoring protein. This led to the discovery of AKAP18ε: an exclusively nuclear isoform that lacks a PKA-anchoring helix. Enzyme-mediated proximity-proteomics reveal that compartment-selective variants of AKAP18 associate with distinct binding partners. Thus, naturally occurring PKA-anchoring-defective AKAP variants not only perturb dissemination of local second-messenger responses, but also may influence the intracellular distribution of certain AKAP18 isoforms.}, } @article {pmid30455319, year = {2018}, author = {Wang, S and Zhuang, Q and Lähteenoja, O and Draper, FC and Cadillo-Quiroz, H}, title = {Potential shift from a carbon sink to a source in Amazonian peatlands under a changing climate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12407-12412}, doi = {10.1073/pnas.1801317115}, pmid = {30455319}, issn = {1091-6490}, abstract = {Amazonian peatlands store a large amount of soil organic carbon (SOC), and its fate under a future changing climate is unknown. Here, we use a process-based peatland biogeochemistry model to quantify the carbon accumulation for peatland and nonpeatland ecosystems in the Pastaza-Marañon foreland basin (PMFB) in the Peruvian Amazon from 12,000 y before present to AD 2100. Model simulations indicate that warming accelerates peat SOC loss, while increasing precipitation accelerates peat SOC accumulation at millennial time scales. The uncertain parameters and spatial variation of climate are significant sources of uncertainty to modeled peat carbon accumulation. Under warmer and presumably wetter conditions over the 21st century, SOC accumulation rate in the PMFB slows down to 7.9 (4.3-12.2) g⋅C⋅m-2⋅y-1 from the current rate of 16.1 (9.1-23.7) g⋅C⋅m-2⋅y-1, and the region may turn into a carbon source to the atmosphere at -53.3 (-66.8 to -41.2) g⋅C⋅m-2⋅y-1 (negative indicates source), depending on the level of warming. Peatland ecosystems show a higher vulnerability than nonpeatland ecosystems, as indicated by the ratio of their soil carbon density changes (ranging from 3.9 to 5.8). This is primarily due to larger peatlands carbon stocks and more dramatic responses of their aerobic and anaerobic decompositions in comparison with nonpeatland ecosystems under future climate conditions. Peatland and nonpeatland soils in the PMFB may lose up to 0.4 (0.32-0.52) Pg⋅C by AD 2100 with the largest loss from palm swamp. The carbon-dense Amazonian peatland may switch from a current carbon sink into a source in the 21st century.}, } @article {pmid30455318, year = {2018}, author = {}, title = {Correction to Supporting Information for Kwon et al., Coiled-coil structure-dependent interactions between polyQ proteins and Foxo lead to dendrite pathology and behavioral defects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11563}, doi = {10.1073/pnas.1818885115}, pmid = {30455318}, issn = {1091-6490}, } @article {pmid30455317, year = {2018}, author = {Fink, AL and Engle, K and Ursin, RL and Tang, WY and Klein, SL}, title = {Biological sex affects vaccine efficacy and protection against influenza in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12477-12482}, doi = {10.1073/pnas.1805268115}, pmid = {30455317}, issn = {1091-6490}, support = {U54 AG062333/AG/NIA NIH HHS/United States ; T32 CA009110/CA/NCI NIH HHS/United States ; HHSN272201400007C/AI/NIAID NIH HHS/United States ; }, abstract = {Biological sex affects adaptive immune responses, which could impact influenza infection and vaccine efficacy. Infection of mice with 2009 H1N1 induced antibody responses, CD4+ T cell and CD8+ T cell memory responses that were greater in females than males; both sexes, however, were equally protected against secondary challenge with an H1N1 drift variant virus. To test whether greater antibody in females is sufficient for protection against influenza, males and females were immunized with an inactivated H1N1 vaccine that induced predominantly antibody-mediated immunity. Following vaccination, females had greater antibody responses and protection against challenge with an H1N1 drift variant virus than males. Antibody derived from vaccinated females was better at protecting both naïve males and females than antibody from males, and this protection was associated with increased antibody specificity and avidity to the H1N1 virus. The expression of Tlr7 was greater in B cells from vaccinated females than males and was associated with reduced DNA methylation in the Tlr7 promoter region, higher neutralizing antibody, class switch recombination, and antibody avidity in females. Deletion of Tlr7 reduced sex differences in vaccine-induced antibody responses and protection following challenge and had a greater impact on responses in females than males. Taken together, these data illustrate that greater TLR7 activation and antibody production in females improves the efficacy of vaccination against influenza.}, } @article {pmid30455316, year = {2018}, author = {Cao, Y and Lei, X and Ribeiro, RM and Perelson, AS and Liang, J}, title = {Probabilistic control of HIV latency and transactivation by the Tat gene circuit.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12453-12458}, doi = {10.1073/pnas.1811195115}, pmid = {30455316}, issn = {1091-6490}, support = {P01 AI131365/AI/NIAID NIH HHS/United States ; R01 AI028433/AI/NIAID NIH HHS/United States ; R01 OD011095/OD/NIH HHS/United States ; R01 CA204962/CA/NCI NIH HHS/United States ; R35 GM127084/GM/NIGMS NIH HHS/United States ; R01 GM126558/GM/NIGMS NIH HHS/United States ; }, abstract = {The reservoir of HIV latently infected cells is the major obstacle for eradication of HIV infection. The "shock-and-kill" strategy proposed earlier aims to reduce the reservoir by activating cells out of latency. While the intracellular HIV Tat gene circuit is known to play important roles in controlling latency and its transactivation in HIV-infected cells, the detailed control mechanisms are not well understood. Here we study the mechanism of probabilistic control of the latent and the transactivated cell phenotypes of HIV-infected cells. We reconstructed the probability landscape, which is the probability distribution of the Tat gene circuit states, by directly computing the exact solution of the underlying chemical master equation. Results show that the Tat circuit exhibits a clear bimodal probability landscape (i.e., there are two distinct probability peaks, one associated with the latent cell phenotype and the other with the transactivated cell phenotype). We explore potential modifications to reactions in the Tat gene circuit for more effective transactivation of latent cells (i.e., the shock-and-kill strategy). Our results suggest that enhancing Tat acetylation can dramatically increase Tat and viral production, while increasing the Tat-transactivation response binding affinity can transactivate latent cells more rapidly than other manipulations. Our results further explored the "block and lock" strategy toward a functional cure for HIV. Overall, our study demonstrates a general approach toward discovery of effective therapeutic strategies and druggable targets by examining control mechanisms of cell phenotype switching via exactly computed probability landscapes of reaction networks.}, } @article {pmid30455315, year = {2018}, author = {}, title = {Correction for Zhao et al., Intestinal virome changes precede autoimmunity in type I diabetes-susceptible children.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11426}, doi = {10.1073/pnas.1817913115}, pmid = {30455315}, issn = {1091-6490}, } @article {pmid30455314, year = {2018}, author = {}, title = {Correction for Sago et al., High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11427}, doi = {10.1073/pnas.1818262115}, pmid = {30455314}, issn = {1091-6490}, } @article {pmid30455313, year = {2018}, author = {Kamelgarn, M and Chen, J and Kuang, L and Jin, H and Kasarskis, EJ and Zhu, H}, title = {ALS mutations of FUS suppress protein translation and disrupt the regulation of nonsense-mediated decay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {51}, pages = {E11904-E11913}, doi = {10.1073/pnas.1810413115}, pmid = {30455313}, issn = {1091-6490}, support = {I01 BX002149/BX/BLRD VA/United States ; R01 NS077284/NS/NINDS NIH HHS/United States ; T32 ES007266/ES/NIEHS NIH HHS/United States ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is an incurable neurodegenerative disease characterized by preferential motor neuron death. Approximately 15% of ALS cases are familial, and mutations in the fused in sarcoma (FUS) gene contribute to a subset of familial ALS cases. FUS is a multifunctional protein participating in many RNA metabolism pathways. ALS-linked mutations cause a liquid-liquid phase separation of FUS protein in vitro, inducing the formation of cytoplasmic granules and inclusions. However, it remains elusive what other proteins are sequestered into the inclusions and how such a process leads to neuronal dysfunction and degeneration. In this study, we developed a protocol to isolate the dynamic mutant FUS-positive cytoplasmic granules. Proteomic identification of the protein composition and subsequent pathway analysis led us to hypothesize that mutant FUS can interfere with protein translation. We demonstrated that the ALS mutations in FUS indeed suppressed protein translation in N2a cells expressing mutant FUS and fibroblast cells derived from FUS ALS cases. In addition, the nonsense-mediated decay (NMD) pathway, which is closely related to protein translation, was altered by mutant FUS. Specifically, NMD-promoting factors UPF1 and UPF3b increased, whereas a negative NMD regulator, UPF3a, decreased, leading to the disruption of NMD autoregulation and the hyperactivation of NMD. Alterations in NMD factors and elevated activity were also observed in the fibroblast cells of FUS ALS cases. We conclude that mutant FUS suppresses protein biosynthesis and disrupts NMD regulation, both of which likely contribute to motor neuron death.}, } @article {pmid30455312, year = {2018}, author = {Sá, JM and Kaslow, SR and Krause, MA and Melendez-Muniz, VA and Salzman, RE and Kite, WA and Zhang, M and Moraes Barros, RR and Mu, J and Han, PK and Mershon, JP and Figan, CE and Caleon, RL and Rahman, RS and Gibson, TJ and Amaratunga, C and Nishiguchi, EP and Breglio, KF and Engels, TM and Velmurugan, S and Ricklefs, S and Straimer, J and Gnädig, NF and Deng, B and Liu, A and Diouf, A and Miura, K and Tullo, GS and Eastman, RT and Chakravarty, S and James, ER and Udenze, K and Li, S and Sturdevant, DE and Gwadz, RW and Porcella, SF and Long, CA and Fidock, DA and Thomas, ML and Fay, MP and Sim, BKL and Hoffman, SL and Adams, JH and Fairhurst, RM and Su, XZ and Wellems, TE}, title = {Artemisinin resistance phenotypes and K13 inheritance in a Plasmodium falciparum cross and Aotus model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12513-12518}, doi = {10.1073/pnas.1813386115}, pmid = {30455312}, issn = {1091-6490}, support = {R01 AI109023/AI/NIAID NIH HHS/United States ; R01 AI117017/AI/NIAID NIH HHS/United States ; R01 AI094973/AI/NIAID NIH HHS/United States ; }, abstract = {Concerns about malaria parasite resistance to treatment with artemisinin drugs (ARTs) have grown with findings of prolonged parasite clearance t1/2s (>5 h) and their association with mutations in Plasmodium falciparum Kelch-propeller protein K13. Here, we describe a P. falciparum laboratory cross of K13 C580Y mutant with C580 wild-type parasites to investigate ART response phenotypes in vitro and in vivo. After genotyping >400 isolated progeny, we evaluated 20 recombinants in vitro: IC50 measurements of dihydroartemisinin were at similar low nanomolar levels for C580Y- and C580-type progeny (mean ratio, 1.00; 95% CI, 0.62-1.61), whereas, in a ring-stage survival assay, the C580Y-type progeny had 19.6-fold (95% CI, 9.76-39.2) higher average counts. In splenectomized Aotus monkeys treated with three daily doses of i.v. artesunate, t1/2 calculations by three different methods yielded mean differences of 0.01 h (95% CI, -3.66 to 3.67), 0.80 h (95% CI, -0.92 to 2.53), and 2.07 h (95% CI, 0.77-3.36) between C580Y and C580 infections. Incidences of recrudescence were 57% in C580Y (4 of 7) versus 70% in C580 (7 of 10) infections (-13% difference; 95% CI, -58% to 35%). Allelic substitution of C580 in a C580Y-containing progeny clone (76H10) yielded a transformant (76H10C580Rev) that, in an infected monkey, recrudesced regularly 13 times over 500 d. Frequent recrudescences of ART-treated P. falciparum infections occur with or without K13 mutations and emphasize the need for improved partner drugs to effectively eliminate the parasites that persist through the ART component of combination therapy.}, } @article {pmid30455311, year = {2018}, author = {Huang, C and Wang, Z and Quinn, D and Suresh, S and Hsia, KJ}, title = {Differential growth and shape formation in plant organs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12359-12364}, doi = {10.1073/pnas.1811296115}, pmid = {30455311}, issn = {1091-6490}, support = {R01 HD086325/HD/NICHD NIH HHS/United States ; }, abstract = {Morphogenesis is a phenomenon by which a wide variety of functional organs are formed in biological systems. In plants, morphogenesis is primarily driven by differential growth of tissues. Much effort has been devoted to identifying the role of genetic and biomolecular pathways in regulating cell division and cell expansion and in influencing shape formation in plant organs. However, general principles dictating how differential growth controls the formation of complex 3D shapes in plant leaves and flower petals remain largely unknown. Through quantitative measurements on live plant organs and detailed finite-element simulations, we show how the morphology of a growing leaf is determined by both the maximum value and the spatial distribution of growth strain. With this understanding, we develop a broad scientific framework for a morphological phase diagram that is capable of rationalizing four configurations commonly found in plant organs: twisting, helical twisting, saddle bending, and edge waving. We demonstrate the robustness of these findings and analyses by recourse to synthetic reproduction of all four configurations using controlled polymerization of a hydrogel. Our study points to potential approaches to innovative geometrical design and actuation in such applications as building architecture, soft robotics and flexible electronics.}, } @article {pmid30455310, year = {2018}, author = {Alameda, L and Fournier, M and Khadimallah, I and Griffa, A and Cleusix, M and Jenni, R and Ferrari, C and Klauser, P and Baumann, PS and Cuenod, M and Hagmann, P and Conus, P and Do, KQ}, title = {Redox dysregulation as a link between childhood trauma and psychopathological and neurocognitive profile in patients with early psychosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12495-12500}, doi = {10.1073/pnas.1812821115}, pmid = {30455310}, issn = {1091-6490}, abstract = {Exposure to childhood trauma (CT) increases the risk for psychosis and affects the development of brain structures, possibly through oxidative stress. As oxidative stress is also linked to psychosis, it may interact with CT, leading to a more severe clinical phenotype. In 133 patients with early psychosis (EPP), we explored the relationships between CT and hippocampal, amygdala, and intracranial volume (ICV); blood antioxidant defenses [glutathione peroxidase (GPx) and thioredoxin/peroxiredoxin (Trx/Prx)]; psychopathological results; and neuropsychological results. Nonadjusted hippocampal volume correlated negatively with GPx activity in patients with CT, but not in patients without CT. In patients with CT with high GPx activity (high-GPx+CT), hippocampal volume was decreased compared with that in patients with low-GPx+CT and patients without CT, who had similar hippocampal volumes. Patients with high-GPx+CT had more severe positive and disorganized symptoms than other patients. Interestingly, Trx and oxidized Prx levels correlated negatively with GPx only in patients with low-GPx+CT. Moreover, patients with low-GPx+CT performed better than other patients on cognitive tasks. Discriminant analysis combining redox markers, hippocampal volume, clinical scores, and cognitive scores allowed for stratification of the patients into subgroups. In conclusion, traumatized EPP with high peripheral oxidation status (high-GPx activity) had smaller hippocampal volumes and more severe symptoms, while those with lower oxidation status (low-GPx activity) showed better cognition and regulation of GPx and Trx/Prx systems. These results suggest that maintained regulation of various antioxidant systems allowed for compensatory mechanisms preventing long-term neuroanatomical and clinical impacts. The redox marker profile may thus represent important biomarkers for defining treatment strategies in patients with psychosis.}, } @article {pmid30455309, year = {2018}, author = {Zhao, B and Zheng, H and Wang, S and Smith, KR and Lu, X and Aunan, K and Gu, Y and Wang, Y and Ding, D and Xing, J and Fu, X and Yang, X and Liou, KN and Hao, J}, title = {Change in household fuels dominates the decrease in PM2.5 exposure and premature mortality in China in 2005-2015.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12401-12406}, doi = {10.1073/pnas.1812955115}, pmid = {30455309}, issn = {1091-6490}, abstract = {To tackle the severe fine particle (PM2.5) pollution in China, the government has implemented stringent control policies mainly on power plants, industry, and transportation since 2005, but estimates of the effectiveness of the policy and the temporal trends in health impacts are subject to large uncertainties. By adopting an integrated approach that combines chemical transport simulation, ambient/household exposure evaluation, and health-impact assessment, we find that the integrated population-weighted exposure to PM2.5 (IPWE) decreased by 47% (95% confidence interval, 37-55%) from 2005 [180 (146-219) μg/m3] to 2015 [96 (83-111) μg/m3]. Unexpectedly, 90% (86-93%) of such reduction is attributed to reduced household solid-fuel use, primarily resulting from rapid urbanization and improved incomes rather than specific control policies. The IPWE due to household fuels for both cooking and heating decreased, but the impact of cooking is significantly larger. The reduced household-related IPWE is estimated to avoid 0.40 (0.25-0.57) million premature deaths annually, accounting for 33% of the PM2.5-induced mortality in 2015. The IPWE would be further reduced by 63% (57-68%) if the remaining household solid fuels were replaced by clean fuels, which would avoid an additional 0.51 (0.40-0.64) million premature deaths. Such a transition to clean fuels, especially for heating, requires technology innovation and policy support to overcome the barriers of high cost of distribution systems, as is recently being attempted in the Beijing-Tianjin-Hebei area. We suggest that household-fuel use be more highly prioritized in national control policies, considering its effects on PM2.5 exposures.}, } @article {pmid30455308, year = {2018}, author = {Liao, X and Li, M and Liu, B and Yan, M and Yu, X and Zi, H and Liu, R and Yamamuro, C}, title = {Interlinked regulatory loops of ABA catabolism and biosynthesis coordinate fruit growth and ripening in woodland strawberry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11542-E11550}, doi = {10.1073/pnas.1812575115}, pmid = {30455308}, issn = {1091-6490}, abstract = {Fruit growth and ripening are controlled by multiple phytohormones. How these hormones coordinate and interact with each other to control these processes at the molecular level is unclear. We found in the early stages of Fragaria vesca (woodland strawberry) fruit development, auxin increases both widths and lengths of fruits, while gibberellin [gibberellic acid (GA)] mainly promotes their longitudinal elongation. Auxin promoted GA biosynthesis and signaling by activating GA biosynthetic and signaling genes, suggesting auxin function is partially dependent on GA function. To prevent the repressive effect of abscisic acid (ABA) on fruit growth, auxin and GA suppressed ABA accumulation during early fruit development by activating the expression of FveCYP707A4a encoding cytochrome P450 monooxygenase that catalyzes ABA catabolism. At the onset of fruit ripening, both auxin and GA levels decreased, leading to a steep increase in the endogenous level of ABA that drives fruit ripening. ABA repressed the expression of FveCYP707A4a but promoted that of FveNCED, a rate-limiting step in ABA biosynthesis. Accordingly, altering FveCYP707A4a expression changed the endogenous ABA levels and affected FveNCED expression. Hence, ABA catabolism and biosynthesis are tightly linked by feedback and feedforward loops to limit ABA contents for fruit growth and to quickly increase ABA contents for the onset of fruit ripening. These results indicate that FveCYP707A4a not only regulates ABA accumulation but also provides a hub to coordinate fruit size and ripening times by relaying auxin, GA, and ABA signals.}, } @article {pmid30455307, year = {2018}, author = {Zhang, Y and Chen, X and Zheng, B and Guo, X and Pan, Y and Chen, H and Li, H and Min, S and Guan, C and Huang, KW and Zheng, J}, title = {Structural analysis of transient reaction intermediate in formic acid dehydrogenation catalysis using two-dimensional IR spectroscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12395-12400}, doi = {10.1073/pnas.1809342115}, pmid = {30455307}, issn = {1091-6490}, abstract = {The molecular structure of a catalytically active key intermediate is determined in solution by employing 2D IR spectroscopy measuring vibrational cross-angles. The formate intermediate (2) in the formic acid dehydrogenation reaction catalyzed by a phosphorus-nitrogen PN3P-Ru catalyst is elucidated. Our spectroscopic studies show that the complex features a formate ion directly attached to the Ru center as a ligand, and a proton added to the imine arm of the dearomatized PN3P* ligand. During the catalytic process, the imine arms are not only reversibly protonated and deprotonated, but also interacting with the protic substrate molecules, effectively serving as the local proton buffer to offer remarkable stability with a turnover number (TON) over one million.}, } @article {pmid30455306, year = {2018}, author = {Tagawa, T and Gao, S and Koparde, VN and Gonzalez, M and Spouge, JL and Serquiña, AP and Lurain, K and Ramaswami, R and Uldrick, TS and Yarchoan, R and Ziegelbauer, JM}, title = {Discovery of Kaposi's sarcoma herpesvirus-encoded circular RNAs and a human antiviral circular RNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12805-12810}, doi = {10.1073/pnas.1816183115}, pmid = {30455306}, issn = {1091-6490}, mesh = {B-Lymphocytes/virology ; Castleman Disease/genetics/virology ; Cell Line ; Endothelial Cells/virology ; Gene Expression Profiling/methods ; Gene Expression Regulation, Viral/genetics ; Genes, Viral/genetics ; HEK293 Cells ; Herpesvirus 8, Human/*genetics ; Human Umbilical Vein Endothelial Cells ; Humans ; Lymphoma, Primary Effusion/genetics/virology ; MicroRNAs/genetics ; Open Reading Frames/genetics ; RNA/*genetics ; RNA, Viral/genetics ; Sarcoma, Kaposi/*genetics/*virology ; }, abstract = {Noncoding RNAs have substantial effects in host-virus interactions. Circular RNAs (circRNAs) are novel single-stranded noncoding RNAs which can decoy other RNAs or RNA-binding proteins to inhibit their functions. The role of circRNAs is largely unknown in the context of Kaposi's sarcoma herpesvirus (KSHV). We hypothesized that circRNAs influence viral infection by inhibiting host and/or viral factors. Transcriptome analysis of KSHV-infected primary endothelial cells and a B cell line identified human circRNAs that are differentially regulated upon infection. We confirmed the expression changes with divergent PCR primers and RNase R treatment of specific circRNAs. Ectopic expression of hsa_circ_0001400, a circRNA induced by infection, suppressed expression of key viral latent gene LANA and lytic gene RTA in KSHV de novo infections. Since human herpesviruses express noncoding RNAs like microRNAs, we searched for viral circRNAs encoded in the KSHV genome. We performed circRNA-Seq analysis with RNase R-treated, circRNA-enriched RNA from KSHV-infected cells. We identified multiple circRNAs encoded by the KSHV genome that are expressed in KSHV-infected endothelial cells and primary effusion lymphoma (PEL) cells. The KSHV circRNAs are located within ORFs of viral lytic genes, are up-regulated upon the induction of the lytic cycle, and alter cell growth. Viral circRNAs were also detected in lymph nodes from patients of KSHV-driven diseases such as PEL, Kaposi's sarcoma, and multicentric Castleman's disease. We revealed new host-virus interactions of circRNAs: human antiviral circRNAs are activated in response to KSHV infection, and viral circRNA expression is induced in the lytic phase of infection.}, } @article {pmid30455305, year = {2018}, author = {Pissaridou, P and Allsopp, LP and Wettstadt, S and Howard, SA and Mavridou, DAI and Filloux, A}, title = {The Pseudomonas aeruginosa T6SS-VgrG1b spike is topped by a PAAR protein eliciting DNA damage to bacterial competitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12519-12524}, doi = {10.1073/pnas.1814181115}, pmid = {30455305}, issn = {1091-6490}, support = {MR/K001930/1//Medical Research Council/United Kingdom ; MR/N023250/1//Medical Research Council/United Kingdom ; BB/N002539/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/M009505/1//Medical Research Council/United Kingdom ; }, abstract = {The type VI secretion system (T6SS) is a supramolecular complex involved in the delivery of potent toxins during bacterial competition. Pseudomonas aeruginosa possesses three T6SS gene clusters and several hcp and vgrG gene islands, the latter encoding the spike at the T6SS tip. The vgrG1b cluster encompasses seven genes whose organization and sequences are highly conserved in P. aeruginosa genomes, except for two genes that we called tse7 and tsi7 We show that Tse7 is a Tox-GHH2 domain nuclease which is distinct from other T6SS nucleases identified thus far. Expression of this toxin induces the SOS response, causes growth arrest and ultimately results in DNA degradation. The cytotoxic domain of Tse7 lies at its C terminus, while the N terminus is a predicted PAAR domain. We find that Tse7 sits on the tip of the VgrG1b spike and that specific residues at the PAAR-VgrG1b interface are essential for VgrG1b-dependent delivery of Tse7 into bacterial prey. We also show that the delivery of Tse7 is dependent on the H1-T6SS cluster, and injection of the nuclease into bacterial competitors is deployed for interbacterial competition. Tsi7, the cognate immunity protein, protects the producer from the deleterious effect of Tse7 through a direct protein-protein interaction so specific that toxin/immunity pairs are effective only if they originate from the same P. aeruginosa isolate. Overall, our study highlights the diversity of T6SS effectors, the exquisite fitting of toxins on the tip of the T6SS, and the specificity in Tsi7-dependent protection, suggesting a role in interstrain competition.}, } @article {pmid30455304, year = {2018}, author = {Tokuyama, M and Kong, Y and Song, E and Jayewickreme, T and Kang, I and Iwasaki, A}, title = {ERVmap analysis reveals genome-wide transcription of human endogenous retroviruses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12565-12572}, doi = {10.1073/pnas.1814589115}, pmid = {30455304}, issn = {1091-6490}, abstract = {Endogenous retroviruses (ERVs) are integrated retroviral elements that make up 8% of the human genome. However, the impact of ERVs on human health and disease is not well understood. While select ERVs have been implicated in diseases, including autoimmune disease and cancer, the lack of tools to analyze genome-wide, locus-specific expression of proviral autonomous ERVs has hampered the progress in the field. Here we describe a method called ERVmap, consisting of an annotated database of 3,220 human proviral ERVs and a pipeline that allows for locus-specific genome-wide identification of proviral ERVs that are transcribed based on RNA-sequencing data, and provide examples of the utility of this tool. Using ERVmap, we revealed cell-type-specific ERV expression patterns in commonly used cell lines as well as in primary cells. We identified 124 unique ERV loci that are significantly elevated in the peripheral blood mononuclear cells of patients with systemic lupus erythematosus that represent an IFN-independent signature. Finally, we identified additional tumor-associated ERVs that correlate with cytolytic activity represented by granzyme and perforin expression in breast cancer tissue samples. The open-source code of ERVmap and the accompanied web tool are made publicly available to quantify proviral ERVs in RNA-sequencing data with ease. Use of ERVmap across a range of diseases and experimental conditions has the potential to uncover novel disease-associated antigens and effectors involved in human health that is currently missed by focusing on protein-coding sequences.}, } @article {pmid30455303, year = {2018}, author = {Swygert, SG and Senapati, S and Bolukbasi, MF and Wolfe, SA and Lindsay, S and Peterson, CL}, title = {SIR proteins create compact heterochromatin fibers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12447-12452}, doi = {10.1073/pnas.1810647115}, pmid = {30455303}, issn = {1091-6490}, support = {R01 AI117839/AI/NIAID NIH HHS/United States ; U54 CA143862/CA/NCI NIH HHS/United States ; }, abstract = {Heterochromatin is a silenced chromatin region essential for maintaining genomic stability and driving developmental processes. The complicated structure and dynamics of heterochromatin have rendered it difficult to characterize. In budding yeast, heterochromatin assembly requires the SIR proteins-Sir3, believed to be the primary structural component of SIR heterochromatin, and the Sir2-4 complex, responsible for the targeted recruitment of SIR proteins and the deacetylation of lysine 16 of histone H4. Previously, we found that Sir3 binds but does not compact nucleosomal arrays. Here we reconstitute chromatin fibers with the complete complement of SIR proteins and use sedimentation velocity, molecular modeling, and atomic force microscopy to characterize the stoichiometry and conformation of SIR chromatin fibers. In contrast to fibers with Sir3 alone, our results demonstrate that SIR arrays are highly compact. Strikingly, the condensed structure of SIR heterochromatin fibers requires both the integrity of H4K16 and an interaction between Sir3 and Sir4. We propose a model in which a dimer of Sir3 bridges and stabilizes two adjacent nucleosomes, while a Sir2-4 heterotetramer interacts with Sir3 associated with a nucleosomal trimer, driving fiber compaction.}, } @article {pmid30455302, year = {2018}, author = {Lagarde, A and Josserand, C and Protière, S}, title = {Oscillating path between self-similarities in liquid pinch-off.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12371-12376}, doi = {10.1073/pnas.1814242115}, pmid = {30455302}, issn = {1091-6490}, abstract = {Many differential equations involved in natural sciences show singular behaviors; i.e., quantities in the model diverge as the solution goes to zero. Nonetheless, the evolution of the singularity can be captured with self-similar solutions, several of which may exist for a given system. How to characterize the transition from one self-similar regime to another remains an open question. By studying the classic example of the pinch-off of a viscous liquid thread, we show experimentally that the geometry of the system and external perturbations play an essential role in the transition from a symmetric to an asymmetric solution. Moreover, this transient regime undergoes unexpected log-scale oscillations that delay dramatically the onset of the final self-similar solution. This result sheds light on the strong impact external constraints can have on predictions established to explain the formation of satellite droplets or on the rheological tests applied on a fluid, for example.}, } @article {pmid30455301, year = {2018}, author = {Galbiati, R and Henry, E and Jacquemet, N}, title = {Dynamic effects of enforcement on cooperation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12425-12428}, doi = {10.1073/pnas.1813502115}, pmid = {30455301}, issn = {1091-6490}, abstract = {In situations where social payoffs are not aligned with private incentives, enforcement with fines can be a way to sustain cooperation. In this paper we show, by the means of a laboratory experiment, that past fines can have an effect on current behavior even when no longer in force. We document two mechanisms: (i) Past fines affect directly individuals' future propensity to cooperate, and (ii) when fines for noncooperation are in place in the past, individuals experience higher levels of cooperation from partners and, consistent with indirect reciprocity motives, are in turn nicer toward others once these fines have been removed. This second mechanism is empirically prevalent and, in contrast with the first one, induces a snowball effect of past enforcement. Our results can inform the design of costly enforcement policies.}, } @article {pmid30455300, year = {2018}, author = {Nicewonger, MR and Aydin, M and Prather, MJ and Saltzman, ES}, title = {Large changes in biomass burning over the last millennium inferred from paleoatmospheric ethane in polar ice cores.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12413-12418}, doi = {10.1073/pnas.1807172115}, pmid = {30455300}, issn = {1091-6490}, abstract = {Biomass burning drives changes in greenhouse gases, climate-forcing aerosols, and global atmospheric chemistry. There is controversy about the magnitude and timing of changes in biomass burning emissions on millennial time scales from preindustrial to present and about the relative importance of climate change and human activities as the underlying cause. Biomass burning is one of two notable sources of ethane in the preindustrial atmosphere. Here, we present ice core ethane measurements from Antarctica and Greenland that contain information about changes in biomass burning emissions since 1000 CE (Common Era). The biomass burning emissions of ethane during the Medieval Period (1000-1500 CE) were higher than present day and declined sharply to a minimum during the cooler Little Ice Age (1600-1800 CE). Assuming that preindustrial atmospheric reactivity and transport were the same as in the modern atmosphere, we estimate that biomass burning emissions decreased by 30 to 45% from the Medieval Period to the Little Ice Age. The timing and magnitude of this decline in biomass burning emissions is consistent with that inferred from ice core methane stable carbon isotope ratios but inconsistent with histories based on sedimentary charcoal and ice core carbon monoxide measurements. This study demonstrates that biomass burning emissions have exceeded modern levels in the past and may be highly sensitive to changes in climate.}, } @article {pmid30455299, year = {2018}, author = {}, title = {Correction to Supporting Information for Nobori et al., Transcriptome landscape of a bacterial pathogen under plant immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11564}, doi = {10.1073/pnas.1818862115}, pmid = {30455299}, issn = {1091-6490}, } @article {pmid30455298, year = {2018}, author = {Woda, J and Wen, T and Oakley, D and Yoxtheimer, D and Engelder, T and Castro, MC and Brantley, SL}, title = {Detecting and explaining why aquifers occasionally become degraded near hydraulically fractured shale gas wells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12349-12358}, doi = {10.1073/pnas.1809013115}, pmid = {30455298}, issn = {1091-6490}, abstract = {Extensive development of shale gas has generated some concerns about environmental impacts such as the migration of natural gas into water resources. We studied high gas concentrations in waters at a site near Marcellus Shale gas wells to determine the geological explanations and geochemical implications. The local geology may explain why methane has discharged for 7 years into groundwater, a stream, and the atmosphere. Gas may migrate easily near the gas wells in this location where the Marcellus Shale dips significantly, is shallow (∼1 km), and is more fractured. Methane and ethane concentrations in local water wells increased after gas development compared with predrilling concentrations reported in the region. Noble gas and isotopic evidence are consistent with the upward migration of gas from the Marcellus Formation in a free-gas phase. This upflow results in microbially mediated oxidation near the surface. Iron concentrations also increased following the increase of natural gas concentrations in domestic water wells. After several months, both iron and SO42- concentrations dropped. These observations are attributed to iron and SO42- reduction associated with newly elevated concentrations of methane. These temporal trends, as well as data from other areas with reported leaks, document a way to distinguish newly migrated methane from preexisting sources of gas. This study thus documents both geologically risky areas and geochemical signatures of iron and SO42- that could distinguish newly leaked methane from older methane sources in aquifers.}, } @article {pmid30455297, year = {2018}, author = {Lee, G and Sherer, NA and Kim, NH and Rajic, E and Kaur, D and Urriola, N and Martini, KM and Xue, C and Goldenfeld, N and Kuhlman, TE}, title = {Testing the retroelement invasion hypothesis for the emergence of the ancestral eukaryotic cell.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12465-12470}, doi = {10.1073/pnas.1807709115}, pmid = {30455297}, issn = {1091-6490}, abstract = {Phylogenetic evidence suggests that the invasion and proliferation of retroelements, selfish mobile genetic elements that copy and paste themselves within a host genome, was one of the early evolutionary events in the emergence of eukaryotes. Here we test the effects of this event by determining the pressures retroelements exert on simple genomes. We transferred two retroelements, human LINE-1 and the bacterial group II intron Ll.LtrB, into bacteria, and find that both are functional and detrimental to growth. We find, surprisingly, that retroelement lethality and proliferation are enhanced by the ability to perform eukaryotic-like nonhomologous end-joining (NHEJ) DNA repair. We show that the only stable evolutionary consequence in simple cells is maintenance of retroelements in low numbers, suggesting how retrotransposition rates and costs in early eukaryotes could have been constrained to allow proliferation. Our results suggest that the interplay between NHEJ and retroelements may have played a fundamental and previously unappreciated role in facilitating the proliferation of retroelements, elements of which became the ancestors of the spliceosome components in eukaryotes.}, } @article {pmid30455296, year = {2018}, author = {}, title = {Correction for Tilman et al., Localized prosocial preferences, public goods, and common-pool resources.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11425}, doi = {10.1073/pnas.1818591115}, pmid = {30455296}, issn = {1091-6490}, } @article {pmid30455295, year = {2018}, author = {}, title = {Correction to Supporting Information for Alix-Garcia et al., Payments for environmental services supported social capital while increasing land management.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11562}, doi = {10.1073/pnas.1818895115}, pmid = {30455295}, issn = {1091-6490}, } @article {pmid30455294, year = {2018}, author = {}, title = {Correction to Supporting Information for Rohrback et al., Submegabase copy number variations arise during cerebral cortical neurogenesis as revealed by single-cell whole-genome sequencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11428}, doi = {10.1073/pnas.1818590115}, pmid = {30455294}, issn = {1091-6490}, } @article {pmid30455293, year = {2018}, author = {Huang, J and Levinson, D and Wang, J and Zhou, J and Wang, ZJ}, title = {Tracking job and housing dynamics with smartcard data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12710-12715}, doi = {10.1073/pnas.1815928115}, pmid = {30455293}, issn = {1091-6490}, abstract = {Residential locations, the jobs-housing relationship, and commuting patterns are key elements to understand urban spatial structure and how city dwellers live. Their successive interaction is important for various fields including urban planning, transport, intraurban migration studies, and social science. However, understanding of the long-term trajectories of workplace and home location, and the resulting commuting patterns, is still limited due to lack of year-to-year data tracking individual behavior. With a 7-y transit smartcard dataset, this paper traces individual trajectories of residences and workplaces. Based on in-metro travel times before and after job and/or home moves, we find that 45 min is an inflection point where the behavioral preference changes. Commuters whose travel time exceeds the point prefer to shorten commutes via moves, while others with shorter commutes tend to increase travel time for better jobs and/or residences. Moreover, we capture four mobility groups: home mover, job hopper, job-and-residence switcher, and stayer. This paper studies how these groups trade off travel time and housing expenditure with their job and housing patterns. Stayers with high job and housing stability tend to be home (apartment unit) owners subject to middle- to high-income groups. Home movers work at places similar to stayers, while they may upgrade from tenancy to ownership. Switchers increase commute time as well as housing expenditure via job and home moves, as they pay for better residences and work farther from home. Job hoppers mainly reside in the suburbs, suffer from long commutes, change jobs frequently, and are likely to be low-income migrants.}, } @article {pmid30455292, year = {2018}, author = {Melnikov, SV and van den Elzen, A and Stevens, DL and Thoreen, CC and Söll, D}, title = {Loss of protein synthesis quality control in host-restricted organisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11505-E11512}, doi = {10.1073/pnas.1815992115}, pmid = {30455292}, issn = {1091-6490}, support = {R35 GM122560/GM/NIGMS NIH HHS/United States ; }, abstract = {Intracellular organisms, such as obligate parasites and endosymbionts, typically possess small genomes due to continuous genome decay caused by an environment with alleviated natural selection. Previously, a few species with highly reduced genomes, including the intracellular pathogens Mycoplasma and Microsporidia, have been shown to carry degenerated editing domains in aminoacyl-tRNA synthetases. These defects in the protein synthesis machinery cause inaccurate translation of the genetic code, resulting in significant statistical errors in protein sequences that are thought to help parasites to escape immune response of a host. In this study we analyzed 10,423 complete bacterial genomes to assess conservation of the editing domains in tRNA synthetases, including LeuRS, IleRS, ValRS, ThrRS, AlaRS, and PheRS. We found that, while the editing domains remain intact in free-living species, they are degenerated in the overwhelming majority of host-restricted bacteria. Our work illustrates that massive genome erosion triggered by an intracellular lifestyle eradicates one of the most fundamental components of a living cell: the system responsible for proofreading of amino acid selection for protein synthesis. This finding suggests that inaccurate translation of the genetic code might be a general phenomenon among intercellular organisms with reduced genomes.}, } @article {pmid30455291, year = {2018}, author = {}, title = {Correction for Benej et al., Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11561}, doi = {10.1073/pnas.1818732115}, pmid = {30455291}, issn = {1091-6490}, } @article {pmid30455290, year = {2018}, author = {Noel, AC and Hu, DL}, title = {Cats use hollow papillae to wick saliva into fur.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12377-12382}, doi = {10.1073/pnas.1809544115}, pmid = {30455290}, issn = {1091-6490}, abstract = {The cat tongue is covered in sharp, rear-facing spines called papillae, the precise function of which is a mystery. In this combined experimental and theoretical study, we use high-speed film, grooming force measurements, and computed tomography (CT) scanning to elucidate the mechanism by which papillae are used to groom fur. We examine the tongues of six species of cats from domestic cat to lion, spanning 30-fold in body weight. The papillae of these cats each feature a hollow cavity at the tip that spontaneously wicks saliva from the mouth and then releases it onto hairs. The unique shape of the cat's papillae may inspire ways to clean complex hairy surfaces. We demonstrate one such application with the tongue-inspired grooming (TIGR) brush, which incorporates 3D-printed cat papillae into a silicone substrate. The TIGR brush experiences lower grooming forces than a normal hairbrush and is easier to clean.}, } @article {pmid30455289, year = {2018}, author = {Pang, Q and Zhou, L and Nazar, LF}, title = {Elastic and Li-ion-percolating hybrid membrane stabilizes Li metal plating.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12389-12394}, doi = {10.1073/pnas.1809187115}, pmid = {30455289}, issn = {1091-6490}, abstract = {Lithium metal batteries are capable of revolutionizing the battery marketplace for electrical vehicles, owing to the high capacity and low voltage offered by Li metal. Current exploitation of Li metal electrodes, however, is plagued by their exhaustive parasitic reactions with liquid electrolytes and dendritic growth, which pose concerns to both cell performance and safety. We demonstrate that a hybrid membrane, both elastic and Li+-ion percolating, can stabilize Li plating/stripping with high Coulombic efficiency. The compact packing of a Li+ solid electrolyte phase offers percolated Li+-conducting channels and the consequent infiltration of an elastic polymer endows membrane flexibility to accommodate volume changes. The protected electrode allows Li plating with 95.8% efficiency for 200 cycles and stable operation of an LTO|Li cell for 2,000 cycles. This rationally structured membrane represents an interface engineering approach toward stabilized Li metal electrodes.}, } @article {pmid30455288, year = {2018}, author = {Wiggins, EB and Czimczik, CI and Santos, GM and Chen, Y and Xu, X and Holden, SR and Randerson, JT and Harvey, CF and Kai, FM and Yu, LE}, title = {Smoke radiocarbon measurements from Indonesian fires provide evidence for burning of millennia-aged peat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12419-12424}, doi = {10.1073/pnas.1806003115}, pmid = {30455288}, issn = {1091-6490}, abstract = {In response to a strong El Niño, fires in Indonesia during September and October 2015 released a large amount of carbon dioxide and created a massive regional smoke cloud that severely degraded air quality in many urban centers across Southeast Asia. Although several lines of evidence indicate that peat burning was a dominant contributor to emissions in the region, El Niño-induced drought is also known to increase deforestation fires and agricultural waste burning in plantations. As a result, uncertainties remain with respect to partitioning emissions among different ecosystem and fire types. Here we measured the radiocarbon content (14C) of carbonaceous aerosol samples collected in Singapore from September 2014 through October 2015, with the aim of identifying the age and origin of fire-emitted fine particulate matter (particulate matter with an aerodynamic diameter less than or equal to 2.5 μm). The Δ14C of fire-emitted aerosol was -76 ± 51‰, corresponding to a carbon pool of combusted organic matter with a mean turnover time of 800 ± 420 y. Our observations indicated that smoke plumes reaching Singapore originated primarily from peat burning (∼85%), and not from deforestation fires or waste burning. Atmospheric transport modeling confirmed that fires in Sumatra and Borneo were dominant contributors to elevated PM2.5 in Singapore during the fire season. The mean age of the carbonaceous aerosol, which predates the Industrial Revolution, highlights the importance of improving peatland fire management during future El Niño events for meeting climate mitigation and air quality commitments.}, } @article {pmid30455219, year = {2018}, author = {Kharouba, HM and Lewthwaite, JMM and Guralnick, R and Kerr, JT and Vellend, M}, title = {Using insect natural history collections to study global change impacts: challenges and opportunities.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455219}, issn = {1471-2970}, abstract = {Over the past two decades, natural history collections (NHCs) have played an increasingly prominent role in global change research, but they have still greater potential, especially for the most diverse group of animals on Earth: insects. Here, we review the role of NHCs in advancing our understanding of the ecological and evolutionary responses of insects to recent global changes. Insect NHCs have helped document changes in insects' geographical distributions, phenology, phenotypic and genotypic traits over time periods up to a century. Recent work demonstrates the enormous potential of NHCs data for examining insect responses at multiple temporal, spatial and phylogenetic scales. Moving forward, insect NHCs offer unique opportunities to examine the morphological, chemical and genomic information in each specimen, thus advancing our understanding of the processes underlying species' ecological and evolutionary responses to rapid, widespread global changes.This article is part of the theme issue 'Biological collections for understanding biodiversity in the anthropocene'.}, } @article {pmid30455218, year = {2018}, author = {MacLean, HJ and Nielsen, ME and Kingsolver, JG and Buckley, LB}, title = {Using museum specimens to track morphological shifts through climate change.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455218}, issn = {1471-2970}, abstract = {Museum specimens offer a largely untapped resource for detecting morphological shifts in response to climate change. However, morphological shifts can be obscured by shifts in phenology or distribution or sampling biases. Additionally, interpreting phenotypic shifts requires distinguishing whether they result from plastic or genetic changes. Previous studies using collections have documented consistent historical size changes, but the limited studies of other morphological traits have often failed to support, or even test, hypotheses. We explore the potential of collections by investigating shifts in the functionally significant coloration of a montane butterfly, Colias meadii, over the past 60 years within three North American geographical regions. We find declines in ventral wing melanism, which correspond to reduced absorption of solar radiation and thus reduced risk of overheating, in two regions. However, contrary to expected responses to climate warming, we find melanism increases in the most thoroughly sampled region. Relationships among temperature, phenology and morphology vary across years and complicate the distinction between plastic and genetic responses. Differences in these relationships may account for the differing morphological shifts among regions. Our findings highlight the promise of using museum specimens to test mechanistic hypotheses for shifts in functional traits, which is essential for deciphering interacting responses to climate change.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455217, year = {2018}, author = {McAllister, CA and McKain, MR and Li, M and Bookout, B and Kellogg, EA}, title = {Specimen-based analysis of morphology and the environment in ecologically dominant grasses: the power of the herbarium.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455217}, issn = {1471-2970}, abstract = {Herbaria contain a cumulative sample of the world's flora, assembled by thousands of people over centuries. To capitalize on this resource, we conducted a specimen-based analysis of a major clade in the grass tribe Andropogoneae, including the dominant species of the world's grasslands in the genera Andropogon, Schizachyrium, Hyparrhenia and several others. We imaged 186 of the 250 named species of the clade, georeferenced the specimens and extracted climatic variables for each. Using semi- and fully automated image analysis techniques, we extracted spikelet morphological characters and correlated these with environmental variables. We generated chloroplast genome sequences to correct for phylogenetic covariance and here present a new phylogeny for 81 of the species. We confirm and extend earlier studies to show that Andropogon and Schizachyrium are not monophyletic. In addition, we find all morphological and ecological characters are homoplasious but variable among clades. For example, sessile spikelet length is positively correlated with awn length when all accessions are considered, but when separated by clade, the relationship is positive for three sub-clades and negative for three others. Climate variables showed no correlation with morphological variation in the spikelet pair; only very weak effects of temperature and precipitation were detected on macrohair density.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455216, year = {2018}, author = {Nic Lughadha, E and Walker, BE and Canteiro, C and Chadburn, H and Davis, AP and Hargreaves, S and Lucas, EJ and Schuiteman, A and Williams, E and Bachman, SP and Baines, D and Barker, A and Budden, AP and Carretero, J and Clarkson, JJ and Roberts, A and Rivers, MC}, title = {The use and misuse of herbarium specimens in evaluating plant extinction risks.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455216}, issn = {1471-2970}, abstract = {Herbarium specimens provide verifiable and citable evidence of the occurrence of particular plants at particular points in space and time, and are vital resources for assessing extinction risk in the tropics, where plant diversity and threats to plants are greatest. We reviewed approaches to assessing extinction risk in response to the Convention on Biological Diversity's Global Strategy for Plant Conservation Target 2: an assessment of the conservation status of all known plant species by 2020. We tested five alternative approaches, using herbarium-derived data for trees, shrubs and herbs in five different plant groups from temperate and tropical regions. All species were previously fully assessed for the IUCN Red List. We found significant variation in the accuracy with which different approaches classified species as threatened or not threatened. Accuracy was highest for the machine learning model (90%) but the least data-intensive approach also performed well (82%). Despite concerns about spatial, temporal and taxonomic biases and uncertainties in herbarium data, when specimens represent the best available evidence for particular species, their use as a basis for extinction risk assessment is appropriate, necessary and urgent. Resourcing herbaria to maintain, increase and disseminate their specimen data is essential to guide and focus conservation action.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455215, year = {2018}, author = {Beaulieu, C and Lavoie, C and Proulx, R}, title = {Bookkeeping of insect herbivory trends in herbarium specimens of purple loosestrife (Lythrum salicaria).}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455215}, issn = {1471-2970}, abstract = {The potential use of herbarium specimens to detect herbivory trends is enormous but largely untapped. The objective of this study was to reconstruct the long-term herbivory pressure on the Eurasian invasive plant, purple loosestrife (Lythrum salicaria), by evaluating leaf damage over 1323 specimens from southern Québec (Canada). The hypothesis tested is that that the prevalence of herbivory damage on purple loosestrife is low during the invasion phase and increases throughout the saturation phase. Historical trends suggest a gradual increase in hole feeding and margin feeding damage from 1883 to around 1940, followed by a period of relative stability. The percentage of specimens with window feeding damage did not begin to increase until the end of the twentieth century, from 3% (2-6%) in 1990 to 45% (14-81%) in 2015. Temporal changes in the frequency of window feeding damage support the hypothesis of an increasing herbivory pressure by recently introduced insects. This study shows that leaf damage made by insects introduced for the biocontrol of purple loosestrife, such as coleopterans of the Neogalerucella genus, can be assessed from voucher specimens. Herbaria are a rich source in information that can be used to answer questions related to plant-insect interactions in the context of biological invasions and biodiversity changes.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455214, year = {2018}, author = {Kling, MM and Mishler, BD and Thornhill, AH and Baldwin, BG and Ackerly, DD}, title = {Facets of phylodiversity: evolutionary diversification, divergence and survival as conservation targets.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455214}, issn = {1471-2970}, abstract = {Biodiversity is often described as having multiple facets, including species richness, functional diversity and phylogenetic diversity. In this paper, we argue that phylogenetic diversity itself has three distinct facets-lineage diversification, character divergence and survival time-that can be quantified using distinct branch length metrics on an evolutionary tree. Each dimension is related to different processes of macroevolution, has different spatial patterns and is tied to distinct goals for conserving biodiversity and protecting its future resilience and evolutionary potential. We compared the landscapes identified as top conservation priorities by each of these three metrics in a conservation gap analysis for California, a world biodiversity hotspot, using herbarium data on the biogeography and evolutionary relationships of more than 5000 native plant species. Our analysis incorporated a novel continuous metric of current land protection status, fine-scale data on landscape intactness and an optimization algorithm used to identify complementary priority sites containing concentrations of taxa that are evolutionarily unique, vulnerable due to small range size and/or poorly protected across their ranges. Top conservation priorities included pockets of coastal and northern California that ranked highly for all three phylodiversity dimensions and for species richness, as well as sites uniquely identified by each metric whose value may depend on whether properties such as genetic divergence, high net diversification or independent survival experience are most desirable in an Anthropocene flora.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455213, year = {2018}, author = {Daru, BH and Bowman, EA and Pfister, DH and Arnold, AE}, title = {A novel proof of concept for capturing the diversity of endophytic fungi preserved in herbarium specimens.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455213}, issn = {1471-2970}, abstract = {Herbarium specimens represent important records of morphological and genetic diversity of plants that inform questions relevant to global change, including species distributions, phenology and functional traits. It is increasingly appreciated that plant microbiomes can influence these aspects of plant biology, but little is known regarding the historic distribution of microbes associated with plants collected in the pre-molecular age. If microbiomes can be observed reliably in herbarium specimens, researchers will gain a new lens with which to examine microbial ecology, evolution, species interactions. Here, we describe a method for accessing historical plant microbiomes from preserved herbarium specimens, providing a proof of concept using two plant taxa from the imperiled boreal biome (Andromeda polifolia and Ledum palustre subsp. groenlandicum, Ericaceae). We focus on fungal endophytes, which occur within symptomless plant tissues such as leaves. Through a three-part approach (i.e. culturing, cloning and next-generation amplicon sequencing via the Illumina MiSeq platform, with extensive controls), we examined endophyte communities in dried, pressed leaves that had been processed as regular herbarium specimens and stored at room temperature in a herbarium for four years. We retrieved only one endophyte in culture, but cloning and especially the MiSeq analysis revealed a rich community of foliar endophytes. The phylogenetic distribution and diversity of endophyte assemblages, especially among the Ascomycota, resemble endophyte communities from fresh plants collected in the boreal biome. We could distinguish communities of endophytes in each plant species and differentiate likely endophytes from fungi that could be surface contaminants. Taxa found by cloning were observed in the larger MiSeq dataset, but species richness was greater when subsets of the same tissues were evaluated with the MiSeq approach. Our findings provide a proof of concept for capturing endophyte DNA from herbarium specimens, supporting the importance of herbarium records as roadmaps for understanding the dynamics of plant-associated microbial biodiversity in the Anthropocene.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455212, year = {2018}, author = {Park, DS and Breckheimer, I and Williams, AC and Law, E and Ellison, AM and Davis, CC}, title = {Herbarium specimens reveal substantial and unexpected variation in phenological sensitivity across the eastern United States.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455212}, issn = {1471-2970}, abstract = {Phenology is a key biological trait that can determine an organism's survival and provides one of the clearest indicators of the effects of recent climatic change. Long time-series observations of plant phenology collected at continental scales could clarify latitudinal and regional patterns of plant responses and illuminate drivers of that variation, but few such datasets exist. Here, we use the web tool CrowdCurio to crowdsource phenological data from over 7000 herbarium specimens representing 30 diverse flowering plant species distributed across the eastern United States. Our results, spanning 120 years and generated from over 2000 crowdsourcers, illustrate numerous aspects of continental-scale plant reproductive phenology. First, they support prior studies that found plant reproductive phenology significantly advances in response to warming, especially for early-flowering species. Second, they reveal that fruiting in populations from warmer, lower latitudes is significantly more phenologically sensitive to temperature than that for populations from colder, higher-latitude regions. Last, we found that variation in phenological sensitivities to climate within species between regions was of similar magnitude to variation between species. Overall, our results suggest that phenological responses to anthropogenic climate change will be heterogeneous within communities and across regions, with large amounts of regional variability driven by local adaptation, phenotypic plasticity and differences in species assemblages. As millions of imaged herbarium specimens become available online, they will play an increasingly critical role in revealing large-scale patterns within assemblages and across continents that ultimately can improve forecasts of the impacts of climatic change on the structure and function of ecosystems.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455211, year = {2018}, author = {Meineke, EK and Davies, TJ}, title = {Museum specimens provide novel insights into changing plant-herbivore interactions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455211}, issn = {1471-2970}, abstract = {Mounting evidence shows that species interactions may mediate how individual species respond to climate change. However, long-term anthropogenic effects on species interactions are poorly characterized owing to a lack of data. Insect herbivory is a major ecological process that represents the interaction between insect herbivores and their host plants, but historical data on insect damage to plants is particularly sparse. Here, we suggest that museum collections of insects and plants can fill key gaps in our knowledge on changing trophic interactions, including proximate mechanisms and the net outcomes of multiple global change drivers across diverse insect herbivore-plant associations. We outline theory on how global change may affect herbivores and their host plants and highlight the unique data that could be extracted from museum specimens to explore their shifting interactions. We aim to provide a framework for using museum specimens to explore how some of the most diverse co-evolved relationships are responding to climate and land use change.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455210, year = {2018}, author = {Andrew, C and Diez, J and James, TY and Kauserud, H}, title = {Fungarium specimens: a largely untapped source in global change biology and beyond.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455210}, issn = {1471-2970}, abstract = {For several hundred years, millions of fungal sporocarps have been collected and deposited in worldwide collections (fungaria) to support fungal taxonomy. Owing to large-scale digitization programs, metadata associated with the records are now becoming publicly available, including information on taxonomy, sampling location, collection date and habitat/substrate information. This metadata, as well as data extracted from the physical fungarium specimens themselves, such as DNA sequences and biochemical characteristics, provide a rich source of information not only for taxonomy but also for other lines of biological inquiry. Here, we highlight and discuss how this information can be used to investigate emerging topics in fungal global change biology and beyond. Fungarium data are a prime source of knowledge on fungal distributions and richness patterns, and for assessing red-listed and invasive species. Information on collection dates has been used to investigate shifts in fungal distributions as well as phenology of sporocarp emergence in response to climate change. In addition to providing material for taxonomy and systematics, DNA sequences derived from the physical specimens provide information about fungal demography, dispersal patterns, and are emerging as a source of genomic data. As DNA analysis technologies develop further, the importance of fungarium specimens as easily accessible sources of information will likely continue to grow.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455209, year = {2018}, author = {Nelson, G and Ellis, S}, title = {The history and impact of digitization and digital data mobilization on biodiversity research.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455209}, issn = {1471-2970}, abstract = {The first two decades of the twenty-first century have seen a rapid rise in the mobilization of digital biodiversity data. This has thrust natural history museums into the forefront of biodiversity research, underscoring their central role in the modern scientific enterprise. The advent of mobilization initiatives such as the United States National Science Foundation's Advancing Digitization of Biodiversity Collections (ADBC), Australia's Atlas of Living Australia (ALA), Mexico's National Commission for the Knowledge and Use of Biodiversity (CONABIO), Brazil's Centro de Referência em Informação (CRIA) and China's National Specimen Information Infrastructure (NSII) has led to a rapid rise in data aggregators and an exponential increase in digital data for scientific research and arguably provide the best evidence of where species live. The international Global Biodiversity Information Facility (GBIF) now serves about 131 million museum specimen records, and Integrated Digitized Biocollections (iDigBio) in the USA has amassed more than 115 million. These resources expose collections to a wider audience of researchers, provide the best biodiversity data in the modern era outside of nature itself and ensure the primacy of specimen-based research. Here, we provide a brief history of worldwide data mobilization, their impact on biodiversity research, challenges for ensuring data quality, their contribution to scientific publications and evidence of the rising profiles of natural history collections.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455208, year = {2018}, author = {Perez, TM and Valverde-Barrantes, O and Bravo, C and Taylor, TC and Fadrique, B and Hogan, JA and Pardo, CJ and Stroud, JT and Baraloto, C and Feeley, KJ}, title = {Botanic gardens are an untapped resource for studying the functional ecology of tropical plants.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455208}, issn = {1471-2970}, abstract = {Functional traits are increasingly used to understand the ecology of plants and to predict their responses to global changes. Unfortunately, trait data are unavailable for the majority of plant species. The lack of trait data is especially prevalent for hard-to-measure traits and for tropical plant species, potentially owing to the many inherent difficulties of working with species in remote, hyperdiverse rainforest systems. The living collections of botanic gardens provide convenient access to large numbers of tropical plant species and can potentially be used to quickly augment trait databases and advance our understanding of species' responses to climate change. In this review, we quantitatively assess the availability of trait data for tropical versus temperate species, the diversity of species available for sampling in several exemplar tropical botanic gardens and the validity of garden-based leaf and root trait measurements. Our analyses support the contention that the living collections of botanic gardens are a valuable scientific resource that can contribute significantly to research on plant functional ecology and conservation.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455207, year = {2018}, author = {Bartomeus, I and Stavert, JR and Ward, D and Aguado, O}, title = {Historical collections as a tool for assessing the global pollination crisis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455207}, issn = {1471-2970}, abstract = {There is increasing concern about the decline of pollinators worldwide. However, despite reports that pollinator declines are widespread, data are scarce and often geographically and taxonomically biased. These biases limit robust inference about any potential pollinator crisis. Non-structured and opportunistic historical specimen collection data provide the only source of historical information which can serve as a baseline for identifying pollinator declines. Specimens historically collected and preserved in museums not only provide information on where and when species were collected, but also contain other ecological information such as species interactions and morphological traits. Here, we provide a synthesis of how researchers have used historical data to identify long-term changes in biodiversity, species abundances, morphology and pollination services. Despite recent advances, we show that information on the status and trends of most pollinators is absent. We highlight opportunities and limitations to progress the assessment of pollinator declines globally. Finally, we demonstrate different approaches to analysing museum collection data using two contrasting case studies from distinct geographical regions (New Zealand and Spain) for which long-term pollinator declines have never been assessed. There is immense potential for museum specimens to play a central role in assessing the extent of the global pollination crisis.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455206, year = {2018}, author = {Soul, LC and Barclay, RS and Bolton, A and Wing, SL}, title = {Fossil Atmospheres: a case study of citizen science in question-driven palaeontological research.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455206}, issn = {1471-2970}, abstract = {Palaeontologists increasingly use large datasets of observations collected from museum specimens to address broad-scale questions about evolution and ecology on geological timescales. One such question is whether information from fossil organisms can be used as a robust proxy for atmospheric carbon dioxide through time. Here, we present the citizen science branch of 'Fossil Atmospheres', a project designed to refine stomatal index of Ginkgo leaves as a palaeo-CO2 proxy by involving citizen scientists in data collection through the Zooniverse website. Citizen science helped to overcome a barrier presented by the time taken to count cells in Ginkgo samples; however, a new set of challenges arose as a result. A beta-testing phase with Zooniverse volunteers provided an opportunity to improve instructions to ensure high fidelity data. Exploration of citizen scientists' estimates shows that volunteer counts of stomata are accurate with respect to counts made by the project's lead scientist. However, counts of epidermal cells have a wide range, and mean values tend to underestimate expert counts. We demonstrate a variety of approaches to reducing the inaccuracy in the calculated stomatal index that this variation causes. Zooniverse serves as an ideal tool for collection of palaeontological data where the distribution of fossils would be impossible, but where specimens can be easily imaged. Such an approach facilitates the collection of a large palaeontological dataset, as well as providing an opportunity for citizens to engage with climate research.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455205, year = {2018}, author = {Schmitt, CJ and Cook, JA and Zamudio, KR and Edwards, SV}, title = {Museum specimens of terrestrial vertebrates are sensitive indicators of environmental change in the Anthropocene.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455205}, issn = {1471-2970}, abstract = {Natural history museums and the specimen collections they curate are vital scientific infrastructure, a fact as true today as it was when biologists began collecting and preserving specimens over 200 years ago. The importance of museum specimens in studies of taxonomy, systematics, ecology and evolutionary biology is evidenced by a rich and abundant literature, yet creative and novel uses of specimens are constantly broadening the impact of natural history collections on biodiversity science and global sustainability. Excellent examples of the critical importance of specimens come from their use in documenting the consequences of environmental change, which is particularly relevant considering the alarming rate at which we now modify our planet in the Anthropocene. In this review, we highlight the important role of bird, mammal and amphibian specimens in documenting the Anthropocene and provide examples that underscore the need for continued collection of museum specimens.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455204, year = {2018}, author = {Meineke, EK and Davies, TJ and Daru, BH and Davis, CC}, title = {Biological collections for understanding biodiversity in the Anthropocene.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {374}, number = {1763}, pages = {}, pmid = {30455204}, issn = {1471-2970}, abstract = {Global change has become a central focus of modern biology. Yet, our knowledge of how anthropogenic drivers affect biodiversity and natural resources is limited by a lack of biological data spanning the Anthropocene. We propose that the hundreds of millions of plant, fungal and animal specimens deposited in natural history museums have the potential to transform the field of global change biology. We suggest that museum specimens are underused, particularly in ecological studies, given their capacity to reveal patterns that are not observable from other data sources. Increasingly, museum specimens are becoming mobilized online, providing unparalleled access to physiological, ecological and evolutionary data spanning decades and sometimes centuries. Here, we describe the diversity of collections data archived in museums and provide an overview of the diverse uses and applications of these data as discussed in the accompanying collection of papers within this theme issue. As these unparalleled resources are under threat owing to budget cuts and other institutional pressures, we aim to shed light on the unique discoveries that are possible in museums and, thus, the singular value of natural history collections in a period of rapid change.This article is part of the theme issue 'Biological collections for understanding biodiversity in the Anthropocene'.}, } @article {pmid30455112, year = {2018}, author = {Hotez, PJ and Bottazzi, ME and Bethony, J and Diemert, DD}, title = {Advancing the Development of a Human Schistosomiasis Vaccine.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.10.005}, pmid = {30455112}, issn = {1471-5007}, abstract = {Three vaccines against human schistosomiasis are in different phases of clinical development, and a fourth is expected to enter the clinic soon. Successful introduction of an efficacious preventive human schistosomiasis vaccine will require integration into existing health systems such as those that deliver childhood vaccines or mass drug administration programs.}, } @article {pmid30455081, year = {2018}, author = {Caron, DA and Hu, SK}, title = {Are We Overestimating Protistan Diversity in Nature?.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.10.009}, pmid = {30455081}, issn = {1878-4380}, abstract = {Documenting the immense diversity of single-celled, eukaryotic organisms (protists) has been a formidable challenge for ecologists. These species were originally defined by morphological criteria, but shortcomings of the morphospecies concept, and a bewildering array of sizes and cellular attributes, has made constructing a taxonomy that is useful for ecologists nearly impossible. Consequently, physiological and genetic information has been integrated to address these shortcomings, and to develop the framework of a unifying taxonomy. DNA sequence information, in particular, has revolutionized studies of protistan diversity. However, the exponential increase in sequence-based protistan species richness published from field surveys in recent years raises the question of whether we have moved beyond characterizing species-level diversity and begun to reveal intraspecies diversity. The answer to that question appears to be 'yes', at least for some protistan lineages. The need to document such microdiversity may be justified, but it is important for protistologists to recognize and acknowledge that possibility, and its consequences.}, } @article {pmid30454907, year = {2018}, author = {Boyer, DM and Harrington, AR}, title = {New estimates of blood flow rates in the vertebral artery of euarchontans and their implications for encephalic blood flow scaling: A response to Seymour and Snelling (2018).}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2018.10.002}, pmid = {30454907}, issn = {1095-8606}, } @article {pmid30454065, year = {2018}, author = {Petry, CJ and Ong, KK and Hughes, IA and Acerini, CL and Dunger, DB}, title = {The influence of maternal pregnancy glucose concentrations on associations between a fetal imprinted gene allele score and offspring size at birth.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {821}, pmid = {30454065}, issn = {1756-0500}, support = {RG1644//Wellbeing of Women/ ; 7500001180//Medical Research Council/United Kingdom ; MC_UU_12015/2//Medical Research Council/United Kingdom ; EW9035322//Evelyn Trust/ ; QLK4-1999-01422//Fifth Framework Programme/ ; 2004/03//world cancer research fund international (gb)/ ; 07/20//Newlife Foundation for Disabled Children/ ; G1001995//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; RG54608//Mothercare Charitable Foundation (GB)/ ; 11/0004241//Diabetes UK/United Kingdom ; }, abstract = {OBJECTIVE: Previously we found that certain fetal imprinted genes represented as an allele score are associated with maternal pregnancy glucose concentrations. Recently it was reported that fetal polymorphisms with strong associations with birth weight tend to mediate these independently of increases in maternal pregnancy glucose concentrations. We therefore investigated whether potential associations between the fetal allele score and birth weight were related to maternal glucose concentrations in the Cambridge Baby Growth Study.

RESULTS: The fetal imprinted gene allele score was positively associated with birth weight (β = 63 (17-109) g/risk allele, β' = 0.113, p = 7.6 × 10-3, n = 405). This association was partially attenuated by adjusting for maternal glucose concentrations (β = 50 (4-95) g/risk allele, β' = 0.089, p = 0.03, n = 405). The allele score was also positively associated with risk of being large for gestational age at birth (odds ratio 1.60 (1.19-2.15) per risk allele, p = 2.1 × 10-3, n = 660) and negatively associated with risk of being small for gestational age at birth (odds ratio 0.65 (0.44-0.96) per risk allele, p = 0.03, n = 660). The large for gestational age at birth association was also partially attenuated by maternal glucose concentrations. These results suggest that associations between the fetal imprinted gene allele score and size at birth are mediated through both glucose-dependent and glucose-independent mechanisms.}, } @article {pmid30454020, year = {2018}, author = {Kebede, AS and Muche, AA and Alene, AG}, title = {Factors associated with adverse pregnancy outcome in Debre Tabor town, Northwest Ethiopia: a case control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {820}, pmid = {30454020}, issn = {1756-0500}, abstract = {OBJECTIVE: The aim of this study was to assess the socioeconomic and demographic factors on adverse pregnancy outcomes.

RESULT: The mean age of cases was 42.2 (± 13.26) years and the mean age of controls was 34.5 (± 12.23) years. Advanced maternal age, low educational status, and early sexual debut showed a significant association with an adverse pregnancy outcome. Mothers in the age group 35-44 years, AOR 2.54 (95% CI 1.27, 5.06), 35-44 years, AOR 2.79 (95% CI 1.27, 6.16) and Mothers with age 55 years and above AOR 4.18 (95% CI 1.73, 9.13) were more likely to have an adverse pregnancy outcome compared to mothers in the age group ≤ 24 years. The low educational status was also found to have an implication on adverse pregnancy outcome. Those mothers with no formal education were two times more likely to develop adverse pregnancy outcome AOR 2.15 (95% CI 1.41, 2.81) and those in primary education AOR 1.6 (95% CI 1.06, 4.6) times more likely compared to those in higher education.}, } @article {pmid30454017, year = {2018}, author = {Mousazadeh, S and Yektatalab, S and Momennasab, M and Parvizy, S}, title = {Job satisfaction and related factors among Iranian intensive care unit nurses.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {823}, pmid = {30454017}, issn = {1756-0500}, abstract = {OBJECTIVES: The aim of this study is to determine the levels of job satisfaction and to collect information about the factors affecting job satisfaction of Iranian ICU hospital nurses.

RESULTS: The participants included 124 nurses working in the ICU section of hospitals in the city of Amol in Iran, who were selected by census method. The instruments for gathering the information included Demographic Information Questionnaire and also the Minnesota Satisfaction Questionnaire. The results revealed that the average score of job satisfaction among ICU nurses was 2.50 ± 0.51. Also job satisfaction among women was higher than men (P = 0.03, t = 0.4). One way analysis of variance showed a significant relation between job satisfaction level with employment status and overtime work. Also older nurses had higher levels of job satisfaction. Hospital directors and managers, can use the results of this study in order to have a deeper understanding of job satisfaction among nurses, and the factors affecting it.}, } @article {pmid30454013, year = {2018}, author = {Jikuzono, T and Horikawa, A and Ishikawa, T and Hirokawa, M and Sugitani, I and Inui, T and Ishibashi, O}, title = {Proteinase K treatment improves RNA recovery from thyroid cells fixed with liquid-based cytology solution.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {822}, pmid = {30454013}, issn = {1756-0500}, support = {JP15K10063//Japan Society for the Promotion of Science/ ; }, abstract = {OBJECTIVE: Fine-needle aspiration biopsy (FNAB), an important diagnostic tool given its simplicity, safety, and cost-effectiveness, is fast becoming a popular procedure in the diagnosis of thyroid diseases. Generally, cells isolated from biopsies are transferred directly to microscope slides to prepare smears for cytopathological examination; however, the technical difficulties of this procedure often cause poor reproducibility, which limits the accuracy of diagnostic results. Liquid-based cytology (LBC), in which isolated cells are collected in a fixative solution, is advantageous in that it facilitates the preparation of homogenous cytological specimens. However, LBC has not been applied to molecular diagnoses, such as RNA expression-based diagnosis, mainly because of difficulties in cell recovery and RNA isolation. This study was aimed to improve RNA extraction from papillary cancer-derived K1 cells and thyroid FNAB specimens suspended in LBC solutions.

RESULTS: K1 cells suspended in CytoRich-Red and CytoRich-Blue, fixatives for LBC, were efficiently recovered by trapping to glass-fiber filters. Importantly, subsequent Proteinase K treatment was essential for efficient RNA extraction from the fixed cells. This finding was also applicable to RNA extraction from CytoRich-Red-fixed thyroid FNAB specimens processed in the same way. Consistently, U6 small nuclear RNA was detected in these RNA samples by reverse transcription-polymerase chain reaction.}, } @article {pmid30453987, year = {2018}, author = {Leite, DMC and Brochet, X and Resch, G and Que, YA and Neves, A and Peña-Reyes, C}, title = {Computational prediction of inter-species relationships through omics data analysis and machine learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {420}, pmid = {30453987}, issn = {1471-2105}, mesh = {Algorithms ; Bacteria/virology ; Bacteriophages/genetics ; Computational Biology/*methods ; *Data Analysis ; *Genomics ; *Machine Learning ; Proteins/chemistry ; Species Specificity ; }, abstract = {BACKGROUND: Antibiotic resistance and its rapid dissemination around the world threaten the efficacy of currently-used medical treatments and call for novel, innovative approaches to manage multi-drug resistant infections. Phage therapy, i.e., the use of viruses (phages) to specifically infect and kill bacteria during their life cycle, is one of the most promising alternatives to antibiotics. It is based on the correct matching between a target pathogenic bacteria and the therapeutic phage. Nevertheless, correctly matching them is a major challenge. Currently, there is no systematic method to efficiently predict whether phage-bacterium interactions exist and these pairs must be empirically tested in laboratory. Herein, we present our approach for developing a computational model able to predict whether a given phage-bacterium pair can interact based on their genome.

RESULTS: Based on public data from GenBank and phagesDB.org, we collected more than a thousand positive phage-bacterium interactions with their complete genomes. In addition, we generated putative negative (i.e., non-interacting) pairs. We extracted, from the collected genomes, a set of informative features based on the distribution of predictive protein-protein interactions and on their primary structure (e.g. amino-acid frequency, molecular weight and chemical composition of each protein). With these features, we generated multiple candidate datasets to train our algorithms. On this base, we built predictive models exhibiting predictive performance of around 90% in terms of F1-score, sensitivity, specificity, and accuracy, obtained on the test set with 10-fold cross-validation.

CONCLUSION: These promising results reinforce the hypothesis that machine learning techniques may produce highly-predictive models accelerating the search of interacting phage-bacteria pairs.}, } @article {pmid30453943, year = {2018}, author = {Devailly, G and Joshi, A}, title = {Insights into mammalian transcription control by systematic analysis of ChIP sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {409}, pmid = {30453943}, issn = {1471-2105}, mesh = {Animals ; Base Sequence ; Chromatin Immunoprecipitation/*methods ; *Data Analysis ; Gene Expression Regulation ; Genetic Loci ; Genetic Predisposition to Disease ; Genome ; Humans ; Mammals/*genetics ; Mice ; Nucleotide Motifs/genetics ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; Transcription Factors/metabolism ; Transcription Initiation Site ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Transcription regulation is a major controller of gene expression dynamics during development and disease, where transcription factors (TFs) modulate expression of genes through direct or indirect DNA interaction. ChIP sequencing has become the most widely used technique to get a genome wide view of TF occupancy in a cell type of interest, mainly due to established standard protocols and a rapid decrease in the cost of sequencing. The number of available ChIP sequencing data sets in public domain is therefore ever increasing, including data generated by individual labs together with consortia such as the ENCODE project.

RESULTS: A total of 1735 ChIP-sequencing datasets in mouse and human cell types and tissues were used to perform bioinformatic analyses to unravel diverse features of transcription control. 1- We used the Heat*seq webtool to investigate global relations across the ChIP-seq samples. 2- We demonstrated that factors have a specific genomic location preferences that are, for most factors, conserved across species. 3- Promoter proximal binding of factors was more conserved across cell types while the distal binding sites are more cell type specific. 4- We identified combinations of factors preferentially acting together in a cellular context. 5- Finally, by integrating the data with disease-associated gene loci from GWAS studies, we highlight the value of this data to associate novel regulators to disease.

CONCLUSION: In summary, we demonstrate how ChIP sequencing data integration and analysis is powerful to get new insights into mammalian transcription control and demonstrate the utility of various bioinformatic tools to generate novel testable hypothesis using this public resource.}, } @article {pmid30453938, year = {2018}, author = {Hall-Swan, S and Crawford, J and Newman, R and Cowen, LJ}, title = {Retraction Note: detangling PPI networks to uncover functionally meaningful clusters.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {113}, pmid = {30453938}, issn = {1752-0509}, abstract = {The authors have retracted this article [1]. After publication they discovered a technical error in the Louvain algorithm with bounded cluster sizes. Correction of this error substantially changed the results for this algorithm and the conclusions drawn in the article were found to be incorrect. The authors will submit a new manuscript for peer review.}, } @article {pmid30453924, year = {2018}, author = {Shi, JY and Huang, H and Li, JX and Lei, P and Zhang, YN and Dong, K and Yiu, SM}, title = {TMFUF: a triple matrix factorization-based unified framework for predicting comprehensive drug-drug interactions of new drugs.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {411}, pmid = {30453924}, issn = {1471-2105}, support = {R03 AA016008/AA/NIAAA NIH HHS/United States ; }, mesh = {*Algorithms ; *Drug Interactions ; Humans ; Least-Squares Analysis ; ROC Curve ; Reproducibility of Results ; }, abstract = {BACKGROUND: A significant number of adverse drug reactions is caused by unexpected Drug-drug interactions (DDIs). The identification of DDIs becomes crucial before the co-prescription of multiple drugs is made. Such a task in clinics or in drug discovery usually requires high costs and numerous limitations, while computational approaches are able to predict potential DDIs effectively by utilizing diverse drug attributes (e.g. side effects). Nevertheless, they're incapable when required to predict enhancive and degressive DDIs, which change increasingly and decreasingly the pharmacological behavior of interacting drugs respectively. The pharmacological change of DDIs is one of the most important factors when making a multi-drug prescription.

RESULTS: In this work, we design a Triple Matrix Factorization-based Unified Framework (TMFUF) to address the above issue. By leveraging a group of side effect entries of drugs, TMFUF achieves the inspiring result (AUC = 0.842 and AUPR = 0.526) in the case of conventional DDI prediction under the traditional screening task. In the comparison with two state-of-the-art approaches, TMFUF demonstrates it superiority by ~ 7% and ~ 20% improvement in terms of AUC and AUPR respectively. More importantly, TMFUF shows its ability in the comprehensive DDI prediction under different screening tasks. Finally, a utilization TMFUF reveals the significant pairs of side effects, which contribute to form enhancive and degressive DDIs, for further clinical validation.

CONCLUSIONS: The proposed TMFUF is first capable to predict both conventional binary DDIs and comprehensive DDIs such that it captures the pharmacological changes caused by DDIs. Furthermore, it provides a unified solution of DDI prediction for two screening scenarios, which involves newly given drugs having no prior interaction. Another advantage is its ability to indicate how significantly the pairs of drug features contribute to form DDIs.}, } @article {pmid30453904, year = {2018}, author = {Salazar, JK and Carstens, CK and Ramachandran, P and Shazer, AG and Narula, SS and Reed, E and Ottesen, A and Schill, KM}, title = {Metagenomics of pasteurized and unpasteurized gouda cheese using targeted 16S rDNA sequencing.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {189}, pmid = {30453904}, issn = {1471-2180}, support = {U19 FD005322/FD/FDA HHS/United States ; U19FD005322//U.S. Food and Drug Administration/ ; }, abstract = {BACKGROUND: The microbiome of cheese is diverse, even within a variety. The metagenomics of cheese is dependent on a vast array of biotic and abiotic factors. Biotic factors include the population of microbiota and their resulting cellular metabolism. Abiotic factors, including the pH, water activity, fat, salt, and moisture content of the cheese matrix, as well as environmental conditions (temperature, humidity, and location of aging), influence the biotic factors. This study assessed the metagenomics of commercial Gouda cheese prepared using pasteurized or unpasteurized cow milk or pasteurized goat milk via 16S rDNA sequencing.

RESULTS: Results were analyzed and compared based on milk pasteurization and source, spatial variability (core, outer, and under the rind), and length of aging (2-4 up to 12-18 months). The dominant organisms in the Gouda cheeses, based on percentage of sequence reads identified at the family or genus levels, were Bacillaceae, Lactococcus, Lactobacillus, Streptococcus, and Staphylococcus. More genus- or family-level (e.g. Bacillaceae) identifications were observed in the Gouda cheeses prepared with unpasteurized cow milk (120) compared with those prepared with pasteurized cow milk (92). When assessing influence of spatial variability on the metagenomics of the cheese, more pronounced differences in bacterial genera were observed in the samples taken under the rind; Brachybacterium, Pseudoalteromonas, Yersinia, Klebsiella, and Weissella were only detected in these samples. Lastly, the aging length of the cheese greatly influenced the number of organisms observed. Twenty-seven additional genus-level identifications were observed in Gouda cheese aged for 12-18 months compared with cheese only aged 2-4 months.

CONCLUSIONS: Collectively, the results of this study are important in determining the typical microbiota associated with Gouda cheese and how the microbiome plays a role in safety and quality.}, } @article {pmid30453900, year = {2018}, author = {Jiménez-Ruiz, J and de la O Leyva-Pérez, M and Vidoy-Mercado, I and Barceló, A and Luque, F}, title = {Transcriptomic time-series analysis of early development in olive from germinated embryos to juvenile tree.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {824}, pmid = {30453900}, issn = {1471-2164}, support = {AGR-5948//Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía/ ; AGL2016-75729//Ministerio de Economía y Competitividad (MINECO)/Agencia Estatal de Investigación (co-financed by the European Regional Development Fund, ERDF)/ ; }, abstract = {BACKGROUND: Despite its relevance, almost no studies account for the genetic control in the early stages of tree development, i.e. from germination on. This study seeks to make a quite complete transcriptome for olive development and to elucidate the dynamic regulation of the transcriptomic response during the early-juvenile period by RNAseq time-series expression analysis. The transcriptome was made from 342,049,597 paired-end reads of 101 bp in length. The assembled transcriptome contained 109,125 unigenes (N50 = 1490 bp, average length = 839).

RESULTS: The time-series-expression analysis showed that, embryonic structures present at the first month after the induction of germination reached a more differentiated state in two-month-old seedlings. Once the plants were between three and four months old and reached a size around 6-7 nodes, the first developmental stages appeared to be complete and the developing seedling became a juvenile plant. In addition, an AGL-gene was rapidly downregulated during the induction of germination. The repression of this gene was very strong, as evidenced by the low levels of gene expression during plant development from the embryonic seedling to undetectable levels of expression in the adult tree. These results suggest that this gene may be involved in seed dormancy and could be a repressor of the germination. Also, an APL1-like olive gene was found to be expressed at high levels during flowering, and was also expressed during the cold incubation in the activation of embryo germination, suggesting a probable role in embryonic development.

CONCLUSIONS: The early development from germination to the juvenile stage of olive seedlings occurred when plants reached a size around 6-7 nodes, and general changes of relevant groups of genes involved in development are described. An AGL-gene was proposed to be involved in germination repression. An APL1-like gene was found to have a probable role in embryonic development.}, } @article {pmid30453896, year = {2018}, author = {Di Gangi, M and Lo Bosco, G and Rizzo, R}, title = {Deep learning architectures for prediction of nucleosome positioning from sequences data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {418}, pmid = {30453896}, issn = {1471-2105}, mesh = {Animals ; Base Sequence ; Databases, Nucleic Acid ; *Deep Learning ; Humans ; Neural Networks (Computer) ; Nucleosomes/*metabolism ; ROC Curve ; Reproducibility of Results ; Saccharomyces cerevisiae/genetics ; }, abstract = {BACKGROUND: Nucleosomes are DNA-histone complex, each wrapping about 150 pairs of double-stranded DNA. Their function is fundamental for one of the primary functions of Chromatin i.e. packing the DNA into the nucleus of the Eukaryote cells. Several biological studies have shown that the nucleosome positioning influences the regulation of cell type-specific gene activities. Moreover, computational studies have shown evidence of sequence specificity concerning the DNA fragment wrapped into nucleosomes, clearly underlined by the organization of particular DNA substrings. As the main consequence, the identification of nucleosomes on a genomic scale has been successfully performed by computational methods using a sequence features representation.

RESULTS: In this work, we propose a deep learning model for nucleosome identification. Our model stacks convolutional layers and Long Short-term Memories to automatically extract features from short- and long-range dependencies in a sequence. Using this model we are able to avoid the feature extraction and selection steps while improving the classification performances.

CONCLUSIONS: Results computed on eleven data sets of five different organisms, from Yeast to Human, show the superiority of the proposed method with respect to the state of the art recently presented in the literature.}, } @article {pmid30453895, year = {2018}, author = {Bushel, PR and Caiment, F and Wu, H and O'Lone, R and Day, F and Calley, J and Smith, A and Li, J}, title = {RATEmiRs: the rat atlas of tissue-specific and enriched miRNAs database.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {825}, pmid = {30453895}, issn = {1471-2164}, abstract = {BACKGROUND: MicroRNAs (miRNAs) regulate gene expression and have been targeted as indicators of environmental/toxicologic stressors. Using the data from our deep sequencing of miRNAs in an extensive sampling of rat tissues, we developed a database called RATEmiRs for the Rat Atlas of Tissue-specific and Enriched miRNAs to allow users to dynamically determine mature-, iso- and pre-miR expression abundance, enrichment and specificity in rat tissues and organs.

RESULTS: Illumina sequencing count data from mapped reads and meta data from the miRNA body atlas consisting of 21 and 23 tissues (14 organs) of toxicologic interest from 12 to 13 week old male and female Sprague Dawley rats respectively, were managed in a relational database with a user-friendly query interface. Data-driven pipelines are available to tailor the identification of tissue-enriched (TE) and tissue-specific (TS) miRNAs. Data-driven organ-specific (OS) pipelines reveal miRNAs that are expressed predominately in a given organ. A user-driven approach is also available to assess the tissue expression of user-specified miRNAs. Using one tissue vs other tissues and tissue(s) of an organ vs other organs, we illustrate the utility of RATEmiRs to facilitate the identification of candidate miRNAs. As a use case example, RATEmiRs revealed two TS miRNAs in the liver: rno-miR-122-3p and rno-miR-122-5p. When liver is compared to just the brain tissues for example, rno-miR-192-5p, rno-miR-193-3p, rno-miR-203b-3p, rno-miR-3559-5p, rno-miR-802-3p and rno-miR-802-5p are also detected as abundantly expressed in liver. As another example, 55 miRNAs from the RATEmiRs query of ileum vs brain tissues overlapped with miRNAs identified from the same comparison of tissues in an independent, publicly available dataset of 10 week old male rat microarray data suggesting that these miRNAs are likely not age-specific, platform-specific nor pipeline-dependent. Lastly, we identified 10 miRNAs that have conserved tissue/organ-specific expression between the rat and human species.

CONCLUSIONS: RATEmiRs provides a new platform for identification of TE, TS and OS miRNAs in a broad array of rat tissues. RATEmiRs is available at: https://www.niehs.nih.gov/ratemirs.}, } @article {pmid30453887, year = {2018}, author = {Corona-Santiago, DK and Domínguez-Domínguez, O and Tovar-Mora, L and Pardos-Blas, JR and Herrerías-Diego, Y and Pérez-Rodríguez, R and Doadrio, I}, title = {Historical biogeography reveals new independent evolutionary lineages in the Pantosteus plebeius-nebuliferus species-group (Actinopterygii: Catostomidae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {173}, pmid = {30453887}, issn = {1471-2148}, mesh = {Animals ; Cypriniformes/*classification/genetics ; Genetic Markers ; Genetic Variation ; Haplotypes/genetics ; Mexico ; *Phylogeny ; *Phylogeography ; Species Specificity ; Time Factors ; }, abstract = {BACKGROUND: The Pantosteus plebeius-nebuliferus species-group is a group of freshwater fishes distributed in endo- and exorheic drainage basins in the Mexican Sierra Madre Occidental mountain range system and central North Mexico. The geological history of this region is considered an important factor in explaining the evolutionary history of low vagility animals like freshwaters fishes. The aim of this study was to examine the phylogenetic relationships and describe the evolutionary history of the species-group. We hypothesized that the genetic structure and distribution of the main clades of Pantosteus plebeius-nebuliferus are associated with the geological history of Northern Mexico. To this end, we obtained DNA sequences of mitochondrial and nuclear genes and performed phylogenetic and phylogeographic analyses. Divergence time estimation and ancestral area reconstruction were also carried out to propose a biogeographical hypothesis, and species boundaries within the species-group were also tested.

RESULTS: We identified four clades within the Pantosteus plebeius-nebuliferus species-group in both markers. Divergence ranged from 5.9% to 9.2% for cytb and 0.1% to 0.9% for GHI. We observed significant genetic structure and no shared haplotypes between clades. We estimated that the clades diverged during the last 5.1 Myr, with a biogeographic scenario suggesting eight vicariant and four dispersal events through the historic range of the species-group. We found that the best species-delimitation model is when four species are assumed, which correspond to the main clades. We identified nine evolutionary significance units (ESUs), pertinent to the conservation of the group, each representing populations present in distinct drainage basins.

CONCLUSIONS: The evolutionary history of the Pantosteus plebeius-nebuliferus species-group is characterized by vicariant post-dispersal processes, linked to geological changes in the Sierra Madre Occidental and central Northern Mexico since the Pliocene. This is congruent with biogeographic patterns described for other co-distributed fish species. We propose a new phylogenetic hypothesis for the species-group, clarifying the taxonomy of this evolutionarily complex group. Our results suggest that the species-group consists of at least four clades with independent evolutionary histories, two of which may represent new undescribed species. Our identification of ESUs provides a basis upon which conservation measures can be developed for the species-group.}, } @article {pmid30453886, year = {2018}, author = {Nasution, MAF and Toepak, EP and Alkaff, AH and Tambunan, USF}, title = {Flexible docking-based molecular dynamics simulation of natural product compounds and Ebola virus Nucleocapsid (EBOV NP): a computational approach to discover new drug for combating Ebola.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {419}, pmid = {30453886}, issn = {1471-2105}, mesh = {Biological Products/*chemistry/pharmacokinetics/toxicity ; Carcinogenicity Tests ; *Drug Discovery ; Ebolavirus/*chemistry ; Hemorrhagic Fever, Ebola ; Humans ; Ligands ; *Molecular Docking Simulation ; *Molecular Dynamics Simulation ; Mutagenicity Tests ; Nucleocapsid/*chemistry ; Thermodynamics ; }, abstract = {BACKGROUND: Ebola still remains as one of the most problematic infectious diseases in Africa with a high rate of mortality. Although this disease has been known for an almost half-century, there are no vaccines and drugs available in the market to treat Ebola. Zaire ebolavirus (EBOV), a single-stranded RNA virus which belongs to Filoviridae family and Mononegavirales order, is one of the virus causing Ebola. As one of seven proteins that EBOV encodes, Ebola virus nucleoprotein (EBOV NP) plays an imperative role in EBOV proliferation cycle. Therefore, the development of a new Ebola treatment can be targeted towards EBOV NP.

RESULTS: In this work, we screened about 190,084 natural product compounds from ZINC15 database through in silico virtual screening and flexible docking simulation. Furthermore, the bioavailability and toxicity prediction have been conducted as well. Two best ligands according to the simulation and prediction tests were progressed into the molecular dynamics simulation.

CONCLUSION: In the end, we found that our proposed ligands, namely α-lipomycin (ZINC56874155) and 3-(((S)-1-amino-1,2,3,4-tetrahydroisoquinolin-5-yl)methyl)-5-((5-((5R,7S)-5,7-dihydroxy-3-oxodecyl)-2-hydroxyphenoxy) methyl)pyrrolo[3,4-b]pyrrol-5-ium (ZINC85628951), showed the promising results to be developed as a lead compounds for treating Ebola. Therefore, an experimental study is required to validate their inhibition activities against EBOV NP.}, } @article {pmid30453885, year = {2018}, author = {Sanz, H and Valim, C and Vegas, E and Oller, JM and Reverter, F}, title = {SVM-RFE: selection and visualization of the most relevant features through non-linear kernels.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {432}, pmid = {30453885}, issn = {1471-2105}, support = {MTM2015-64465-C2-1-R//MINECO/FEDER/ ; MTM2015-64465-C2-1-R//MINECO/FEDER/ ; }, mesh = {*Algorithms ; Biomarkers, Tumor/*genetics ; *Computer Graphics ; Humans ; Liver Cirrhosis, Biliary/genetics/*mortality ; Lung Neoplasms/genetics/*mortality ; Lymphoma, Large B-Cell, Diffuse/genetics/*mortality ; *Support Vector Machine ; Survival Rate ; }, abstract = {BACKGROUND: Support vector machines (SVM) are a powerful tool to analyze data with a number of predictors approximately equal or larger than the number of observations. However, originally, application of SVM to analyze biomedical data was limited because SVM was not designed to evaluate importance of predictor variables. Creating predictor models based on only the most relevant variables is essential in biomedical research. Currently, substantial work has been done to allow assessment of variable importance in SVM models but this work has focused on SVM implemented with linear kernels. The power of SVM as a prediction model is associated with the flexibility generated by use of non-linear kernels. Moreover, SVM has been extended to model survival outcomes. This paper extends the Recursive Feature Elimination (RFE) algorithm by proposing three approaches to rank variables based on non-linear SVM and SVM for survival analysis.

RESULTS: The proposed algorithms allows visualization of each one the RFE iterations, and hence, identification of the most relevant predictors of the response variable. Using simulation studies based on time-to-event outcomes and three real datasets, we evaluate the three methods, based on pseudo-samples and kernel principal component analysis, and compare them with the original SVM-RFE algorithm for non-linear kernels. The three algorithms we proposed performed generally better than the gold standard RFE for non-linear kernels, when comparing the truly most relevant variables with the variable ranks produced by each algorithm in simulation studies. Generally, the RFE-pseudo-samples outperformed the other three methods, even when variables were assumed to be correlated in all tested scenarios.

CONCLUSIONS: The proposed approaches can be implemented with accuracy to select variables and assess direction and strength of associations in analysis of biomedical data using SVM for categorical or time-to-event responses. Conducting variable selection and interpreting direction and strength of associations between predictors and outcomes with the proposed approaches, particularly with the RFE-pseudo-samples approach can be implemented with accuracy when analyzing biomedical data. These approaches, perform better than the classical RFE of Guyon for realistic scenarios about the structure of biomedical data.}, } @article {pmid30453884, year = {2018}, author = {Lee, SH and Ahn, WY and Seweryn, M and Sadee, W}, title = {Combined genetic influence of the nicotinic receptor gene cluster CHRNA5/A3/B4 on nicotine dependence.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {826}, pmid = {30453884}, issn = {1471-2164}, support = {U01 GM092655/GM/NIGMS NIH HHS/United States ; UL1 RR025755/RR/NCRR NIH HHS/United States ; U01 GM092655//National Institutes of Health/ ; }, abstract = {BACKGROUND: The CHRNA5/A3/B4 gene locus is associated with nicotine dependence and other smoking related disorders. While the non-synonymous CHRNA5 variant rs16969968 appears to be the main risk factor, linkage disequilibrium (LD) bins in the gene cluster carry frequent variants that regulate expression. Pairwise LD and haplotype analyses had identified at least three haplotype tagging SNPs including rs16969968 as main genetic risk factors. Searching for variants with evidence of regulatory functions, we have reported interactions between CHRNA5 and CHRNA3 enhancer variants (tagged by rs880395 and rs1948, respectively) and rs16969968, forming 3-SNP haplotypes and diplotypes that may more accurately reflect the cluster's combined effects on nicotine dependence (Barrie et al., Hum Mutat 38:112-9, 2017). Here we address further contributions by variants affecting CHRNB4, a possibly limiting component of nicotinic receptors.

RESULTS: We identify an LD bin (tagged by rs4887074) associated with expression of CHRNB4. Additive logistic regression models indicate that rs4887074 is associated with nicotine dependence and modulates the effect of rs16969968 in GWAS datasets (COGEND, UW-TTURC, SAGE). 4-SNP haplotype and diplotype analyses (rs880395-rs16969968-rs1948 -rs4887074) yield nicotine dependence risk values that further differentiate those obtained with the 3-SNP model. Moreover, both the main G allele of rs16969968 and the minor G allele of rs4887074 (associated with reduced expression of CHRNB4), residing predominantly on common haplotypes that are protective, represent significant allele-specific variance QTLs, indicating that they interact with each other.

CONCLUSIONS: These results indicate rs4887074 is associated with CHRNB4 expression, and along with two regulatory variants of CHRNA3 and CHRNA5, modulates the effect of rs16969968 on nicotine dependence risk. Assignable to individuals because of strong LD structures, 4-SNP haplotypes and diplotypes serve to assess the combined genetic influence of this multi-gene cluster on complex traits, accounting for complex LD relationships and tissue-specific genetic effects (CHRNA5/3) relevant to the traits analyzed. The 4-SNP haplotypes account at least in part for previous tagging SNPs, including the highly GWAS-significant rs6495308, located in a distinct pair-wise LD bin but included in protective 4-SNP haplotypes. Our approach refines and integrates the cluster's overall genetic influence, an important variable when integrating the genetics of multiple genomic loci.}, } @article {pmid30453883, year = {2018}, author = {Polychronidou, E and Kalamaras, I and Agathangelidis, A and Sutton, LA and Yan, XJ and Bikos, V and Vardi, A and Mochament, K and Chiorazzi, N and Belessi, C and Rosenquist, R and Ghia, P and Stamatopoulos, K and Vlamos, P and Chailyan, A and Overby, N and Marcatili, P and Hatzidimitriou, A and Tzovaras, D}, title = {Automated shape-based clustering of 3D immunoglobulin protein structures in chronic lymphocytic leukemia.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {414}, pmid = {30453883}, issn = {1471-2105}, mesh = {Amino Acid Sequence ; Automation ; Databases, Protein ; Humans ; *Imaging, Three-Dimensional ; Immunoglobulins/*chemistry ; Leukemia, Lymphocytic, Chronic, B-Cell/*metabolism ; Molecular Sequence Annotation ; }, abstract = {BACKGROUND: Although the etiology of chronic lymphocytic leukemia (CLL), the most common type of adult leukemia, is still unclear, strong evidence implicates antigen involvement in disease ontogeny and evolution. Primary and 3D structure analysis has been utilised in order to discover indications of antigenic pressure. The latter has been mostly based on the 3D models of the clonotypic B cell receptor immunoglobulin (BcR IG) amino acid sequences. Therefore, their accuracy is directly dependent on the quality of the model construction algorithms and the specific methods used to compare the ensuing models. Thus far, reliable and robust methods that can group the IG 3D models based on their structural characteristics are missing.

RESULTS: Here we propose a novel method for clustering a set of proteins based on their 3D structure focusing on 3D structures of BcR IG from a large series of patients with CLL. The method combines techniques from the areas of bioinformatics, 3D object recognition and machine learning. The clustering procedure is based on the extraction of 3D descriptors, encoding various properties of the local and global geometrical structure of the proteins. The descriptors are extracted from aligned pairs of proteins. A combination of individual 3D descriptors is also used as an additional method. The comparison of the automatically generated clusters to manual annotation by experts shows an increased accuracy when using the 3D descriptors compared to plain bioinformatics-based comparison. The accuracy is increased even more when using the combination of 3D descriptors.

CONCLUSIONS: The experimental results verify that the use of 3D descriptors commonly used for 3D object recognition can be effectively applied to distinguishing structural differences of proteins. The proposed approach can be applied to provide hints for the existence of structural groups in a large set of unannotated BcR IG protein files in both CLL and, by logical extension, other contexts where it is relevant to characterize BcR IG structural similarity. The method does not present any limitations in application and can be extended to other types of proteins.}, } @article {pmid30453881, year = {2018}, author = {Gorlov, IP and Pikielny, CW and Frost, HR and Her, SC and Cole, MD and Strohbehn, SD and Wallace-Bradley, D and Kimmel, M and Gorlova, OY and Amos, CI}, title = {Gene characteristics predicting missense, nonsense and frameshift mutations in tumor samples.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {430}, pmid = {30453881}, issn = {1471-2105}, support = {U19 CA148127/CA/NCI NIH HHS/United States ; DMS-1361411//National Science Foundation/ ; CA149462//National Institutes of Health/ ; K01 LM012426/LM/NLM NIH HHS/United States ; P01 CA206980/CA/NCI NIH HHS/United States ; R56 LM012371/LM/NLM NIH HHS/United States ; Pilot Project//Institutional Prouty Grant, Dartmouth College/ ; R01 CA149462/CA/NCI NIH HHS/United States ; CA206980-01A1//National Institutes of Health/ ; K01LM012426//National Institutes of Health/ ; U19 CA148127//National Institutes of Health/ ; }, mesh = {*Codon, Nonsense ; *Frameshift Mutation ; Humans ; Mutation Rate ; *Mutation, Missense ; Neoplasm Proteins/*genetics ; Neoplasms/*genetics ; }, abstract = {BACKGROUND: Because driver mutations provide selective advantage to the mutant clone, they tend to occur at a higher frequency in tumor samples compared to selectively neutral (passenger) mutations. However, mutation frequency alone is insufficient to identify cancer genes because mutability is influenced by many gene characteristics, such as size, nucleotide composition, etc. The goal of this study was to identify gene characteristics associated with the frequency of somatic mutations in the gene in tumor samples.

RESULTS: We used data on somatic mutations detected by genome wide screens from the Catalog of Somatic Mutations in Cancer (COSMIC). Gene size, nucleotide composition, expression level of the gene, relative replication time in the cell cycle, level of evolutionary conservation and other gene characteristics (totaling 11) were used as predictors of the number of somatic mutations. We applied stepwise multiple linear regression to predict the number of mutations per gene. Because missense, nonsense, and frameshift mutations are associated with different sets of gene characteristics, they were modeled separately. Gene characteristics explain 88% of the variation in the number of missense, 40% of nonsense, and 23% of frameshift mutations. Comparisons of the observed and expected numbers of mutations identified genes with a higher than expected number of mutations- positive outliers. Many of these are known driver genes. A number of novel candidate driver genes was also identified.

CONCLUSIONS: By comparing the observed and predicted number of mutations in a gene, we have identified known cancer-associated genes as well as 111 novel cancer associated genes. We also showed that adding the number of silent mutations per gene reported by genome/exome wide screens across all cancer type (COSMIC data) as a predictor substantially exceeds predicting accuracy of the most popular cancer gene predicting tool - MutsigCV.}, } @article {pmid30453880, year = {2018}, author = {Bian, X and Zhu, B and Wang, M and Hu, Y and Chen, Q and Nguyen, C and Hicks, B and Meerzaman, D}, title = {Comparing the performance of selected variant callers using synthetic data and genome segmentation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {429}, pmid = {30453880}, issn = {1471-2105}, mesh = {*Genome, Human ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Molecular Sequence Annotation ; *Mutation ; *Polymorphism, Single Nucleotide ; Precision Medicine ; }, abstract = {BACKGROUND: High-throughput sequencing has rapidly become an essential part of precision cancer medicine. But validating results obtained from analyzing and interpreting genomic data remains a rate-limiting factor. The gold standard, of course, remains manual validation by expert panels, which is not without its weaknesses, namely high costs in both funding and time as well as the necessarily selective nature of manual validation. But it may be possible to develop more economical, complementary means of validation. In this study we employed four synthetic data sets (variants with known mutations spiked into specific genomic locations) of increasing complexity to assess the sensitivity, specificity, and balanced accuracy of five open-source variant callers: FreeBayes v1.0, VarDict v11.5.1, MuTect v1.1.7, MuTect2, and MuSE v1.0rc. FreeBayes, VarDict, and MuTect were run in bcbio-next gen, and the results were integrated into a single Ensemble call set. The known mutations provided a level of "ground truth" against which we evaluated variant-caller performance. We further facilitated the comparison and evaluation by segmenting the whole genome into 10,000,000 base-pair fragments which yielded 316 segments.

RESULTS: Differences among the numbers of true positives were small among the callers, but the numbers of false positives varied much more when the tools were used to analyze sets one through three. Both FreeBayes and VarDict produced strikingly more false positives than did the others, although VarDict, somewhat paradoxically also produced the highest number of true positives. The Ensemble approach yielded results characterized by higher specificity and balanced accuracy and fewer false positives than did any of the five tools used alone. Sensitivity and specificity, however, declined for all five callers as the complexity of the data sets increased, but we did not uncover anything more than limited, weak correlations between caller performance and certain DNA structural features: gene density and guanine-cytosine content. Altogether, MuTect2 performed the best among the callers tested, followed by MuSE and MuTect.

CONCLUSIONS: Spiking data sets with specific mutations -single-nucleotide variations (SNVs), single-nucleotide polymorphisms (SNPs), or structural variations (SVs) in this study-at known locations in the genome provides an effective and economical way to compare data analyzed by variant callers with ground truth. The method constitutes a viable alternative to the prolonged, expensive, and noncomprehensive assessment by expert panels. It should be further developed and refined, as should other comparatively "lightweight" methods of assessing accuracy. Given that the scientific community has not yet established gold standards for validating NGS-related technologies such as variant callers, developing multiple alternative means for verifying variant-caller accuracy will eventually lead to the establishment of higher-quality standards than could be achieved by prematurely limiting the range of innovative methods explored by members of the community.}, } @article {pmid30453879, year = {2018}, author = {Boldi, P and Frasca, M and Malchiodi, D}, title = {Evaluating the impact of topological protein features on the negative examples selection.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {417}, pmid = {30453879}, issn = {1471-2105}, mesh = {Algorithms ; Animals ; Gene Ontology ; Gene Regulatory Networks ; Humans ; Mice ; Proteins/*chemistry ; Proteome/metabolism ; Saccharomyces cerevisiae/metabolism ; }, abstract = {BACKGROUND: Supervised machine learning methods when applied to the problem of automated protein-function prediction (AFP) require the availability of both positive examples (i.e., proteins which are known to possess a given protein function) and negative examples (corresponding to proteins not associated with that function). Unfortunately, publicly available proteome and genome data sources such as the Gene Ontology rarely store the functions not possessed by a protein. Thus the negative selection, consisting in identifying informative negative examples, is currently a central and challenging problem in AFP. Several heuristics have been proposed through the years to solve this problem; nevertheless, despite their effectiveness, to the best of our knowledge no previous existing work studied which protein features are more relevant to this task, that is, which protein features help more in discriminating reliable and unreliable negatives.

RESULTS: The present work analyses the impact of several features on the selection of negative proteins for the Gene Ontology (GO) terms. The analysis is network-based: it exploits the fact that proteins can be naturally structured in a network, considering the pairwise relationships coming from several sources of data, such as protein-protein and genetic interactions. Overall, the proposed protein features, including local and global graph centrality measures and protein multifunctionality, can be term-aware (i.e., depending on the GO term) and term-unaware (i.e., invariant across the GO terms). We validated the informativeness of each feature utilizing a temporal holdout in three different experiments on yeast, mouse and human proteomes: (i) feature selection to detect which protein features are more helpful for the negative selection; (ii) protein function prediction to verify whether the features considered are also useful to predict GO terms; (iii) negative selection by applying two different negative selection algorithms on proteins represented through the proposed features.

CONCLUSIONS: Term-aware features (with some exceptions) resulted more informative for problem (i), together with node betweenness, which is the most relevant among term-unaware features. The node positive neighborhood instead is the most predictive feature for the AFP problem, while experiment (iii) showed that the proposed features allow negative selection algorithms to select effectively negative instances in the temporal holdout setting, with better results when nonlinear combinations of features are also exploited.}, } @article {pmid30453878, year = {2018}, author = {Mier, P and Pérez-Pulido, AJ and Andrade-Navarro, MA}, title = {Automated selection of homologs to track the evolutionary history of proteins.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {431}, pmid = {30453878}, issn = {1471-2105}, support = {AN735/4-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {*Databases, Protein ; *Evolution, Molecular ; Humans ; Proteins/*metabolism ; Proteome/*analysis ; *Software ; }, abstract = {BACKGROUND: The selection of distant homologs of a query protein under study is a usual and useful application of protein sequence databases. Such sets of homologs are often applied to investigate the function of a protein and the degree to which experimental results can be transferred from one organism to another. In particular, a variety of databases facilitates static browsing for orthologs. However, these resources have a limited power when identifying orthologs between taxonomically distant species. In addition, in some situations, for a given query protein, it is advantageous to compare the sets of orthologs from different specific organisms: this recursive step-wise search might give an idea of the evolutionary path of the protein as a series of consecutive steps, for example gaining or losing domains. However, a step-wise orthology search is a time-consuming task if the number of steps is high.

RESULTS: To illustrate a solution for this problem, we present the web tool ProteinPathTracker, which allows to track the evolutionary history of a query protein by locating homologs in selected proteomes along several evolutionary paths. Additional functionalities include locking a region of interest to follow its evolution in the discovered homologous sequences and the study of the protein function evolution by analysis of the annotations of the homologs.

CONCLUSIONS: ProteinPathTracker is an easy-to-use web tool that automatises the practice of looking for selected homologs in distant species in a straightforward way for non-expert users.}, } @article {pmid30453877, year = {2018}, author = {Pérez-Serrano, J and Sandes, E and Magalhaes Alves de Melo, AC and Ujaldón, M}, title = {DNA sequences alignment in multi-GPUs: acceleration and energy payoff.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {421}, pmid = {30453877}, issn = {1471-2105}, mesh = {*Acceleration ; Algorithms ; Animals ; Base Sequence ; *Computer Graphics ; Electric Power Supplies ; Humans ; Pan troglodytes/genetics ; *Sequence Alignment ; Time Factors ; }, abstract = {BACKGROUND: We present a performance per watt analysis of CUDAlign 4.0, a parallel strategy to obtain the optimal pairwise alignment of huge DNA sequences in multi-GPU platforms using the exact Smith-Waterman method.

RESULTS: Our study includes acceleration factors, performance, scalability, power efficiency and energy costs. We also quantify the influence of the contents of the compared sequences, identify potential scenarios for energy savings on speculative executions, and calculate performance and energy usage differences among distinct GPU generations and models. For a sequence alignment on chromosome-wide scale (around 2 Petacells), we are able to reduce execution times from 9.5 h on a Kepler GPU to just 2.5 h on a Pascal counterpart, with energy costs cut by 60%.

CONCLUSIONS: We find GPUs to be an order of magnitude ahead in performance per watt compared to Xeon Phis. Finally, versus typical low-power devices like FPGAs, GPUs keep similar GFLOPS/w ratios in 2017 on a five times faster execution.}, } @article {pmid30453876, year = {2018}, author = {Li, Y and Maleki, M and Carruthers, NJ and Stemmer, PM and Ngom, A and Rueda, L}, title = {The predictive performance of short-linear motif features in the prediction of calmodulin-binding proteins.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {410}, pmid = {30453876}, issn = {1471-2105}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Bayes Theorem ; Calcium/metabolism ; Calmodulin-Binding Proteins/*chemistry ; Computational Biology/*methods ; Humans ; Probability ; Protein Structure, Quaternary ; Reproducibility of Results ; Support Vector Machine ; }, abstract = {BACKGROUND: The prediction of calmodulin-binding (CaM-binding) proteins plays a very important role in the fields of biology and biochemistry, because the calmodulin protein binds and regulates a multitude of protein targets affecting different cellular processes. Computational methods that can accurately identify CaM-binding proteins and CaM-binding domains would accelerate research in calcium signaling and calmodulin function. Short-linear motifs (SLiMs), on the other hand, have been effectively used as features for analyzing protein-protein interactions, though their properties have not been utilized in the prediction of CaM-binding proteins.

RESULTS: We propose a new method for the prediction of CaM-binding proteins based on both the total and average scores of known and new SLiMs in protein sequences using a new scoring method called sliding window scoring (SWS) as features for the prediction module. A dataset of 194 manually curated human CaM-binding proteins and 193 mitochondrial proteins have been obtained and used for testing the proposed model. The motif generation tool, Multiple EM for Motif Elucidation (MEME), has been used to obtain new motifs from each of the positive and negative datasets individually (the SM approach) and from the combined negative and positive datasets (the CM approach). Moreover, the wrapper criterion with random forest for feature selection (FS) has been applied followed by classification using different algorithms such as k-nearest neighbors (k-NN), support vector machines (SVM), naive Bayes (NB) and random forest (RF).

CONCLUSIONS: Our proposed method shows very good prediction results and demonstrates how information contained in SLiMs is highly relevant in predicting CaM-binding proteins. Further, three new CaM-binding motifs have been computationally selected and biologically validated in this study, and which can be used for predicting CaM-binding proteins.}, } @article {pmid30453875, year = {2018}, author = {Alborzi, SZ and Ritchie, DW and Devignes, MD}, title = {Computational discovery of direct associations between GO terms and protein domains.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {413}, pmid = {30453875}, issn = {1471-2105}, mesh = {Algorithms ; Amino Acid Sequence ; Area Under Curve ; Computational Biology/*methods ; Databases, Protein ; *Gene Ontology ; Molecular Sequence Annotation ; Protein Domains ; Proteins/*chemistry ; }, abstract = {BACKGROUND: Families of related proteins and their different functions may be described systematically using common classifications and ontologies such as Pfam and GO (Gene Ontology), for example. However, many proteins consist of multiple domains, and each domain, or some combination of domains, can be responsible for a particular molecular function. Therefore, identifying which domains should be associated with a specific function is a non-trivial task.

RESULTS: We describe a general approach for the computational discovery of associations between different sets of annotations by formalising the problem as a bipartite graph enrichment problem in the setting of a tripartite graph. We call this approach "CODAC" (for COmputational Discovery of Direct Associations using Common Neighbours). As one application of this approach, we describe "GODomainMiner" for associating GO terms with protein domains. We used GODomainMiner to predict GO-domain associations between each of the 3 GO ontology namespaces (MF, BP, and CC) and the Pfam, CATH, and SCOP domain classifications. Overall, GODomainMiner yields average enrichments of 15-, 41- and 25-fold GO-domain associations compared to the existing GO annotations in these 3 domain classifications, respectively.

CONCLUSIONS: These associations could potentially be used to annotate many of the protein chains in the Protein Databank and protein sequences in UniProt whose domain composition is known but which currently lack GO annotation.}, } @article {pmid30453874, year = {2018}, author = {Seoane, P and Espigares, M and Carmona, R and Polonio, Á and Quintana, J and Cretazzo, E and Bota, J and Pérez-García, A and Dios Alché, J and Gómez, L and Claros, MG}, title = {TransFlow: a modular framework for assembling and assessing accurate de novo transcriptomes in non-model organisms.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {416}, pmid = {30453874}, issn = {1471-2105}, mesh = {Base Pairing/genetics ; Fungi/genetics ; Gene Expression Profiling ; Plants/genetics ; Principal Component Analysis ; Reproducibility of Results ; *Sequence Analysis, RNA ; *Software ; Transcriptome/*genetics ; Workflow ; }, abstract = {BACKGROUND: The advances in high-throughput sequencing technologies are allowing more and more de novo assembling of transcriptomes from many new organisms. Some degree of automation and evaluation is required to warrant reproducibility, repetitivity and the selection of the best possible transcriptome. Workflows and pipelines are becoming an absolute requirement for such a purpose, but the issue of assembling evaluation for de novo transcriptomes in organisms lacking a sequenced genome remains unsolved. An automated, reproducible and flexible framework called TransFlow to accomplish this task is described.

RESULTS: TransFlow with its five independent modules was designed to build different workflows depending on the nature of the original reads. This architecture enables different combinations of Illumina and Roche/454 sequencing data, and can be extended to other sequencing platforms. Its capabilities are illustrated with the selection of reliable plant reference transcriptomes and the assembling six transcriptomes (three case studies for grapevine leaves, olive tree pollen, and chestnut stem, and other three for haustorium, epiphytic structures and their combination for the phytopathogenic fungus Podosphaera xanthii). Arabidopsis and poplar transcriptomes revealed to be the best references. A common result regarding de novo assemblies is that Illumina paired-end reads of 100 nt in length assembled with OASES can provide reliable transcriptomes, while the contribution of longer reads is noticeable only when they complement a set of short, single-reads.

CONCLUSIONS: TransFlow can handle up to 181 different assembling strategies. Evaluation based on principal component analyses allows its self-adaptation to different sets of reads to provide a suitable transcriptome for each combination of reads and assemblers. As a result, each case study has its own behaviour, prioritises evaluation parameters, and gives an objective and automated way for detecting the best transcriptome within a pool of them. Sequencing data type and quantity (preferably several hundred millions of 2×100 nt or longer), assemblers (OASES for Illumina, MIRA4 and EULER-SR reconciled with CAP3 for Roche/454) and strategy (preferably scaffolding with OASES, and probably merging with Roche/454 when available) arise as the most impacting factors.}, } @article {pmid30453873, year = {2018}, author = {Knight, VB and Serrano, EE}, title = {Expression analysis of RNA sequencing data from human neural and glial cell lines depends on technical replication and normalization methods.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {412}, pmid = {30453873}, issn = {1471-2105}, support = {R25 NS080685/NS/NINDS NIH HHS/United States ; }, mesh = {Base Sequence ; Cell Line ; Gene Expression Profiling ; *Gene Expression Regulation ; Humans ; Imaging, Three-Dimensional ; Metabolic Networks and Pathways ; Neural Stem Cells/metabolism ; Neuroglia/*metabolism ; Neurons/*metabolism ; Principal Component Analysis ; RNA/genetics ; Reproducibility of Results ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: The potential for astrocyte participation in central nervous system recovery is highlighted by in vitro experiments demonstrating their capacity to transdifferentiate into neurons. Understanding astrocyte plasticity could be advanced by comparing astrocytes with stem cells. RNA sequencing (RNA-seq) is ideal for comparing differences across cell types. However, this novel multi-stage process has the potential to introduce unwanted technical variation at several points in the experimental workflow. Quantitative understanding of the contribution of experimental parameters to technical variation would facilitate the design of robust RNA-Seq experiments.

RESULTS: RNA-Seq was used to achieve biological and technical objectives. The biological aspect compared gene expression between normal human fetal-derived astrocytes and human neural stem cells cultured in identical conditions. When differential expression threshold criteria of |log2 fold change| > 2 were applied to the data, no significant differences were observed. The technical component quantified variation arising from particular steps in the research pathway, and compared the ability of different normalization methods to reduce unwanted variance. To facilitate this objective, a liberal false discovery rate of 10% and a |log2 fold change| > 0.5 were implemented for the differential expression threshold. Data were normalized with RPKM, TMM, and UQS methods using JMP Genomics. The contributions of key replicable experimental parameters (cell lot; library preparation; flow cell) to variance in the data were evaluated using principal variance component analysis. Our analysis showed that, although the variance for every parameter is strongly influenced by the normalization method, the largest contributor to technical variance was library preparation. The ability to detect differentially expressed genes was also affected by normalization; differences were only detected in non-normalized and TMM-normalized data.

CONCLUSIONS: The similarity in gene expression between astrocytes and neural stem cells supports the potential for astrocytic transdifferentiation into neurons, and emphasizes the need to evaluate the therapeutic potential of astrocytes for central nervous system damage. The choice of normalization method influences the contributions to experimental variance as well as the outcomes of differential expression analysis. However irrespective of normalization method, our findings illustrate that library preparation contributed the largest component of technical variance.}, } @article {pmid30453872, year = {2018}, author = {Yaneske, E and Angione, C}, title = {The poly-omics of ageing through individual-based metabolic modelling.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 14}, pages = {415}, pmid = {30453872}, issn = {1471-2105}, mesh = {Adult ; Aging/*genetics/*metabolism ; Cluster Analysis ; Female ; *Genomics ; Humans ; Male ; Middle Aged ; *Models, Biological ; Principal Component Analysis ; Regression Analysis ; T-Lymphocytes/metabolism ; Young Adult ; }, abstract = {BACKGROUND: Ageing can be classified in two different ways, chronological ageing and biological ageing. While chronological age is a measure of the time that has passed since birth, biological (also known as transcriptomic) ageing is defined by how time and the environment affect an individual in comparison to other individuals of the same chronological age. Recent research studies have shown that transcriptomic age is associated with certain genes, and that each of those genes has an effect size. Using these effect sizes we can calculate the transcriptomic age of an individual from their age-associated gene expression levels. The limitation of this approach is that it does not consider how these changes in gene expression affect the metabolism of individuals and hence their observable cellular phenotype.

RESULTS: We propose a method based on poly-omic constraint-based models and machine learning in order to further the understanding of transcriptomic ageing. We use normalised CD4 T-cell gene expression data from peripheral blood mononuclear cells in 499 healthy individuals to create individual metabolic models. These models are then combined with a transcriptomic age predictor and chronological age to provide new insights into the differences between transcriptomic and chronological ageing. As a result, we propose a novel metabolic age predictor.

CONCLUSIONS: We show that our poly-omic predictors provide a more detailed analysis of transcriptomic ageing compared to gene-based approaches, and represent a basis for furthering our knowledge of the ageing mechanisms in human cells.}, } @article {pmid30453035, year = {2019}, author = {Meegaskumbura, M and Senevirathne, G and Manamendra-Arachchi, K and Pethiyagoda, R and Hanken, J and Schneider, CJ}, title = {Diversification of shrub frogs (Rhacophoridae, Pseudophilautus) in Sri Lanka - Timing and geographic context.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {14-24}, doi = {10.1016/j.ympev.2018.11.004}, pmid = {30453035}, issn = {1095-9513}, abstract = {Pseudophilautus comprises an endemic diversification predominantly associated with the wet tropical regions of Sri Lanka that provides an opportunity to examine the effects of geography and historical climate change on diversification. Using a time-calibrated multi-gene phylogeny, we analyze the tempo of diversification in the context of past climate and geography to identify historical drivers of current patterns of diversity and distribution. Molecular dating suggests that the diversification was seeded by migration across a land-bridge connection from India during a period of climatic cooling and drying, the Oi-1 glacial maximum around the Eocene-Oligocene boundary. Lineage-through-time plots suggest a gradual and constant rate of diversification, beginning in the Oligocene and extending through the late Miocene and early Pliocene with a slight burst in the Pleistocene. There is no indication of an early-burst phase of diversification characteristic of many adaptive radiations, nor were there bursts of diversification associated with favorable climate shifts such as the intensification of monsoons. However, a late Miocene (8.8 MYA) back-migration to India occurred following the establishment of the monsoon. The back migration did not trigger a diversification in India similar to that manifest in Sri Lanka, likely due to occupation of available habitat, and consequent lack of ecological opportunity, by the earlier radiation of a sister lineage of frogs (Raorchestes) with similar ecology. Phylogenetic area reconstructions show a pattern of sister species distributed across adjacent mountain ranges or from different parts of large montane regions, highlighting the importance of isolation and allopatric speciation. Hence, local species communities are composed of species from disparate clades that, in most cases, have been assembled through migration rather than in situ speciation. Lowland lineages are derived from montane lineages. Thus, the hills of Sri Lanka acted as species pumps as well as refuges throughout the 31 million years of evolution, highlighting the importance of tropical montane regions for both the generation and maintenance of biodiversity.}, } @article {pmid30452702, year = {2018}, author = {}, title = {IMPUTOR: Phylogenetically Aware Software for Imputation of Errors in Next-Generation Sequencing.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2931}, doi = {10.1093/gbe/evy221}, pmid = {30452702}, issn = {1759-6653}, } @article {pmid30452654, year = {2018}, author = {Bengoechea, JA and Pessoa, JS}, title = {Klebsiella pneumoniae infection biology: living to counteract host defences.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuy043}, pmid = {30452654}, issn = {1574-6976}, abstract = {Klebsiella species cause a wide range of diseases including pneumonia, UTIs, bloodstream infections, and sepsis. These infections are particularly a problem among neonates, elderly and immunocompromised individuals. Klebsiella is also responsible for a significant number of community-acquired infections. A defining feature of these infections is their morbidity and mortality, and the Klebsiella strains associated with them are considered hypervirulent. The increasing isolation of multidrug resistant strains has significantly narrowed, or in some settings completely removed, the therapeutic options for the treatment of Klebsiella infections. Not surprisingly, this pathogen has then been singled out as an 'urgent threat to human health' by several organizations. This review summarizes the tremendous progress has been made to uncover the sophisticated immune evasion strategies of K. pneumoniae. The co-evolution of Klebsiella in response to the challenge of an activated immune has made Klebsiella a formidable pathogen exploiting stealth strategies and actively suppressing innate immune defences to overcome host responses to survive in the tissues. A better understanding of Klebsiella immune evasion strategies in the context of the host-pathogen interactions is pivotal to develop new therapeutics, which can be based on antagonizing the anti-immune strategies of this pathogen.}, } @article {pmid30452121, year = {2018}, author = {Rhie, MN and Cho, YB and Lee, YJ and Kim, OB}, title = {High-affinity l-malate transporter DcuE of Actinobacillus succinogenes catalyses reversible exchange of C4-dicarboxylates.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12719}, pmid = {30452121}, issn = {1758-2229}, support = {NRF-2015R1A4A1041997//National Research Foundation of Korea/ ; NRF-2015R1C1A2A01053608//National Research Foundation of Korea/ ; }, abstract = {Actinobacillus succinogenes is a natural succinate producer, which is the result of fumarate respiration. Succinate production from anaerobic growth with C4 -dicarboxylates requires transporters catalysing uptake and efflux of C4 -dicarboxylates. Transporter Asuc_1999 (DcuE) found in A. succinogenes belongs to the Dcu family and was considered the main transporter for fumarate respiration. However, deletion of dcuE affected l-malate uptake of A. succinogenes rather than fumarate uptake. DcuE complemented anaerobic growth of Escherichia coli on l-malate or fumarate; thus, the transporter was characterized in E. coli heterologously. Time-dependent uptake and competitive inhibition assays demonstrated that l-malate is the most preferred substrate for uptake by DcuE. The Vmax of DcuE for l-malate was 20.04 μmol/gDW·min with Km of 57 μM. The Vmax for l-malate was comparable to that for fumarate, whereas the Km for l-malate was 8 times lower than that for fumarate. The catalytic efficiency of DcuE for l-malate was 7.3-fold higher than that for fumarate, showing high efficiency and high affinity for l-malate. Furthermore, DcuE catalysed the reversible exchange of three C4 -dicarboxylates - l-malate, fumarate and succinate - but the preferred substrate for uptake was l-malate. Under physiological conditions, the C4 -dicarboxylates were reduced to succinate. Therefore, DcuE is proposed as the l-malate/succinate antiporter in A. succinogenes.}, } @article {pmid30452116, year = {2019}, author = {Shi, Y and Pan, C and Cen, S and Fu, L and Cao, X and Wang, H and Wang, K and Wu, B}, title = {Comparative metabolomics reveals defence-related modification of citrinin by Penicillium citrinum within a synthetic Penicillium-Pseudomonas community.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {496-510}, doi = {10.1111/1462-2920.14482}, pmid = {30452116}, issn = {1462-2920}, support = {2018YFC0311002//National Key Research and Development Program of China/ ; 41876148//National Natural Science Foundation of China/ ; 81573306//National Natural Science Foundation of China/ ; }, abstract = {Co-occurring microorganisms have been proved to influence the performance of each other by metabolic means in nature. Here we generated a synthetic fungal-bacterial community comprising Penicillium citrinum and Pseudomonas aeruginosa employing the previously described membrane-separated co-culture device. By applying a newly designed molecular networking routine, new citrinin-related metabolites induced by the fungal-bacterial cross-talk were unveiled in trace amounts. A mechanically cycled co-culture setup with external pumping forces accelerating the chemically interspecies communication was then developed to boost the production of cross-talk-induced metabolites. Multivariate data analysis combined with molecular networking revealed the accumulation of a pair of co-culture-induced molecules whose productions were positively correlated to the exchange rate in the new co-cultures, facilitating the discovery of the previously undescribed antibiotic citrinolide with a novel skeleton. This highly oxidized citrinin adduct showed significantly enhanced antibiotic property against the partner strain P. aeruginosa than its precursor citrinin, suggesting a role in the microbial competition. Thus, we propose competitive-advantage-oriented structural modification driven by microbial defence response mechanism in the interspecies cross-talk might be a promising approach in the search for novel antibiotics. Besides, this study highlights the utility of MS-based metabolomics as an effective tool in the direct biochemical analysis of the community metabolism.}, } @article {pmid30452115, year = {2018}, author = {Balmonte, JP and Buckley, A and Hoarfrost, A and Ghobrial, S and Ziervogel, K and Teske, A and Arnosti, C}, title = {Community structural differences shape microbial responses to high molecular weight organic matter.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14485}, pmid = {30452115}, issn = {1462-2920}, support = {13328811736772//Division of Ocean Sciences/ ; }, abstract = {The extent to which differences in microbial community structure result in variations in organic matter (OM) degradation is not well understood. Here, we tested the hypothesis that distinct marine microbial communities from North Atlantic surface and bottom waters would exhibit varying compositional succession and functional shifts in response to the same pool of complex high molecular weight (HMW-OM). We also hypothesized that microbial communities would produce a broader spectrum of enzymes upon exposure to HMW-OM, indicating a greater potential to degrade these compounds than reflected by initial enzymatic activities. Our results show that community succession in amended mesocosms was congruent with cell growth, increased bacterial production and most notably, with substantial shifts in enzymatic activities. In all amended mesocosms, closely related taxa that were initially rare became dominant at time frames during which a broader spectrum of active enzymes were detected compared to initial timepoints, indicating a similar response among different communities. However, succession on the whole-community level, and the rates, spectra and progression of enzymatic activities, reveal robust differences among distinct communities from discrete water masses. These results underscore the crucial role of rare bacterial taxa in ocean carbon cycling and the importance of bacterial community structure for HMW-OM degradation.}, } @article {pmid30452113, year = {2018}, author = {Gisder, S and Möckel, N and Eisenhardt, D and Genersch, E}, title = {In vivo evolution of viral virulence: switching of deformed wing virus between hosts results in virulence changes and sequence shifts.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4612-4628}, doi = {10.1111/1462-2920.14481}, pmid = {30452113}, issn = {1462-2920}, support = {1234/2007//European Commission/ ; 1308/2013//European Commission/ ; SMARTBEES FP7-KBBE.2013.1.3-02//Seventh Framework Programme/ ; }, abstract = {The health of the Western honey bee is threatened by a global epidemic of deformed wing virus (DWV) infections driven by the ectoparasitic mite Varroa destructor acting as mechanical and biological virus vector. Three different variants of DWV, DWV-A, -B and -C exist. Virulence differences between these variants and their relation to V. destructor are still controversially discussed. We performed laboratory experiments to analyze the virulence of DWV directly isolated from crippled bees (DWVP0) or after one additional passage in bee pupae (DWVP1). We demonstrated that DWVP0 was more virulent than DWVP1 for pupae, when pupal mortality was taken as virulence marker, and for adult bees, when neurotropism and cognitive impairment were taken as virulence markers. Phylogenetic analysis supported that DWV exists as quasispecies and showed that DWVP0 clustered with DWV-B and DWVP1 with DWV-A when the phylogeny was based on the master sequences of the RNA-dependent RNA polymerase but not so when it was based on the VP3 region master sequences. We propose that switching of DWV between the bee and the mite host is accompanied by changes in viral sequence, tissue tropism and virulence and that the RNA-dependent RNA polymerase is involved in determining host range and virulence.}, } @article {pmid30452111, year = {2018}, author = {Berry, D and Mace, W and Rehner, SA and Grage, K and Dijkwel, PP and Young, CA and Scott, B}, title = {Orthologous peramine and pyrrolopyrazine-producing biosynthetic gene clusters in Metarhizium rileyi, Metarhizium majus and Cladonia grayi.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14483}, pmid = {30452111}, issn = {1462-2920}, support = {//Bio-Protection Research Centre/ ; //Massey University/ ; }, abstract = {Peramine is a non-ribosomal peptide-derived pyrrolopyrazine (PPZ)-containing molecule with anti-insect properties. Peramine is known to be produced by fungi from genus Epichloë, which form mutualistic endophytic associations with cool-season grass hosts. Peramine biosynthesis has been proposed to require only the two-module non-ribosomal peptide synthetase (NRPS) peramine synthetase (PerA), which is encoded by the 8.3 kb gene perA, though this has not been conclusively proven. Until recently, both peramine and perA were thought to be exclusive to fungi of genus Epichloë; however, a putative perA homologue was recently identified in the genome of the insect-pathogenic fungus Metarhizium rileyi. We use a heterologous expression system and a hydrophilic interaction chromatography-based analysis method to confirm that PerA is the only pathway-specific protein required for peramine biosynthesis. The perA homologue from M. rileyi (MR_perA) is shown to encode a functional peramine synthetase, establishing a precedent for distribution of perA orthologs beyond genus Epichloë. Furthermore, perA is part of a larger seven-gene PPZ cluster in M. rileyi, Metarhizium majus and the stalked-cup lichen fungus Cladonia grayi. These PPZ genes encode proteins predicted to derivatize peramine into more complex PPZ metabolites, with the orphaned perA gene of Epichloë spp. representing an example of reductive evolution.}, } @article {pmid30452102, year = {2019}, author = {Nesbø, CL and Charchuk, R and Pollo, SMJ and Budwill, K and Kublanov, IV and Haverkamp, THA and Foght, J}, title = {Genomic analysis of the mesophilic Thermotogae genus Mesotoga reveals phylogeographic structure and genomic determinants of its distinct metabolism.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {456-470}, doi = {10.1111/1462-2920.14477}, pmid = {30452102}, issn = {1462-2920}, support = {18-44-04024//Russian Science Foundation/ ; //Genome Canada/ ; 180444/V40//Research Council of Norway/ ; }, abstract = {The genus Mesotoga, the only described mesophilic Thermotogae lineage, is common in mesothermic anaerobic hydrocarbon-rich environments. Besides mesophily, Mesotoga displays lineage-specific phenotypes, such as no or little H2 production and dependence on sulfur-compound reduction, which may influence its ecological role. We used comparative genomics of 18 Mesotoga strains (pairwise 16S rRNA identity >99%) and a transcriptome of M. prima to investigate how life at moderate temperatures affects phylogeography and to interrogate the genomic features of its lineage-specific metabolism. We propose that Mesotoga accomplish H2 oxidation and thiosulfate reduction using a sulfide dehydrogenase and a hydrogenase-complex and that a pyruvate:ferredoxin oxidoreductase acquired from Clostridia is responsible for oxidizing acetate. Phylogenetic analysis revealed three distinct Mesotoga lineages (89.6%-99.9% average nucleotide identity [ANI] within lineages, 79.3%-87.6% ANI between lineages) having different geographic distribution patterns and high levels of intra-lineage recombination but little geneflow between lineages. Including data from metagenomes, phylogeographic patterns suggest that geographical separation historically has been more important for Mesotoga than hyperthermophilic Thermotoga and we hypothesize that distribution of Mesotoga is constrained by their anaerobic lifestyle. Our data also suggest that recent anthropogenic activities and environments (e.g., wastewater treatment, oil exploration) have expanded Mesotoga habitats and dispersal capabilities.}, } @article {pmid30452101, year = {2019}, author = {Bednarz, VN and van de Water, JAJM and Rabouille, S and Maguer, JF and Grover, R and Ferrier-Pagès, C}, title = {Diazotrophic community and associated dinitrogen fixation within the temperate coral Oculina patagonica.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {480-495}, doi = {10.1111/1462-2920.14480}, pmid = {30452101}, issn = {1462-2920}, abstract = {Dinitrogen (N2) fixing bacteria (diazotrophs) are an important source of new nitrogen in oligotrophic environments and represent stable members of the microbiome in tropical corals, while information on corals from temperate oligotrophic regions is lacking. Therefore, this study provides new insights into the diversity and activity of diazotrophs associated with the temperate coral Oculina patagonica from the Mediterranean Sea by combining metabarcoding sequencing of amplicons of both the 16S rRNA and nifH genes and 15 N2 stable isotope tracer analysis to assess diazotroph-derived nitrogen (DDN) assimilation by the coral. Results show that the diazotrophic community of O. patagonica is dominated by autotrophic bacteria (i.e. Cyanobacteria and Chlorobia). The majority of DDN was assimilated into the tissue and skeletal matrix, and DDN assimilation significantly increased in bleached corals. Thus, diazotrophs may constitute an additional nitrogen source for the coral host, when nutrient exchange with Symbiodinium is disrupted (e.g. bleaching) and external food supply is limited (e.g. oligotrophic summer season). Furthermore, we hypothesize that DDN can facilitate the fast proliferation of endolithic algae, which provide an alternative carbon source for bleached O. patagonica. Overall, O. patagonica could serve as a good model for investigating the importance of diazotrophs in coral recovery from bleaching.}, } @article {pmid30451981, year = {2018}, author = {Fedorov, AK and Kiktenko, EO and Lvovsky, AI}, title = {Quantum computers put blockchain security at risk.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {465-467}, doi = {10.1038/d41586-018-07449-z}, pmid = {30451981}, issn = {1476-4687}, } @article {pmid30451980, year = {2018}, author = {Lewis-Jones, H}, title = {The environment: what's in a word?.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {468-469}, doi = {10.1038/d41586-018-07463-1}, pmid = {30451980}, issn = {1476-4687}, } @article {pmid30451391, year = {2018}, author = {Zhao, Z and Peng, T and Oh, JI and Glaeser, J and Weber, L and Li, Q and Klug, G}, title = {A response regulator of the OmpR family is part of the regulatory network controlling the oxidative stress response of Rhodobacter sphaeroides.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12718}, pmid = {30451391}, issn = {1758-2229}, support = {2015RC27//Sichuan University of Science and Engineering/ ; Kl563/20//DFG/ ; }, abstract = {As a free-living bacterium Rhodobacter sphaeroides needs to respond to many environmental stresses. Oxidative stress, membrane stress or heat stress induce the ompR-1 gene encoding a protein of the OmpR family. Overexpression of OmpR-1 results in increased resistance to organic peroxides and diamide. Our data demonstrate that OmpR-1 positively affects expression of several sRNAs with an established role in R. sphaeroides stress defences and negatively affects the promoter of the rpoHI gene. The RpoHI sigma factor has a main role in the activation of many stress responses. Thus OmpR-1 has a balancing effect on the activation of the RpoHI regulon. We present a model with OmpR-1 as part of a regulatory network controlling stress defences in R. sphaeroides.}, } @article {pmid30451380, year = {2018}, author = {Le Guernic, A and Geffard, A and Rioult, D and Bonnard, I and Le Foll, F and Palos Ladeiro, M}, title = {First evidence of cytotoxic effects of human protozoan parasites on zebra mussel (Dreissena polymorpha) haemocytes.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12720}, pmid = {30451380}, issn = {1758-2229}, support = {//ANR MOBIDIC/ ; }, abstract = {The interaction between human protozoan parasites and the immune cells of bivalves, that can accumulate them, is poorly described. The purpose of this study is to consider the mechanisms of action of some of these protozoa on zebra mussel haemocytes, by evaluating their cytotoxic potential. Haemocytes were exposed to Toxoplasma gondii, Giardia duodenalis or Cryptosporidium parvum (oo)cysts. The results showed a cytotoxic potency of the two largest protozoa on haemocytes and suggested the formation of haemocyte aggregates. Thus, this study reveals the first signs of a haemocyte:protozoan interaction.}, } @article {pmid30451355, year = {2018}, author = {Liu, Y and Brandt, D and Ishino, S and Ishino, Y and Koonin, EV and Kalinowski, J and Krupovic, M and Prangishvili, D}, title = {New archaeal viruses discovered by metagenomic analysis of viral communities in enrichment cultures.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14479}, pmid = {30451355}, issn = {1462-2920}, support = {685778//European Union's Horizon 2020/ ; }, abstract = {Viruses infecting hyperthermophilic archaea of the phylum Crenarchaeota display enormous morphological and genetic diversity, and are classified into 12 families. Eight of these families include only one or two species, indicating sparse sampling of the crenarchaeal virus diversity. In an attempt to expand the crenarchaeal virome, we explored virus diversity in the acidic, hot spring Umi Jigoku in Beppu, Japan. Environmental samples were used to establish enrichment cultures under conditions favouring virus replication. The host diversity in the enrichment cultures was restricted to members of the order Sulfolobales. Metagenomic sequencing of the viral communities yielded seven complete or near-complete double-stranded DNA virus genomes. Six of these genomes could be attributed to polyhedral and filamentous viruses that were observed by electron microscopy in the enrichment cultures. Two icosahedral viruses represented species in the family Portogloboviridae. Among the filamentous viruses, two were identified as new species in the families Rudiviridae and Lipothrixviridae, whereas two other formed a group seemingly distinct from the known virus genera. No particle morphotype could be unequivocally assigned to the seventh viral genome, which apparently represents a new virus type. Our results suggest that filamentous viruses are globally distributed and are prevalent virus types in extreme geothermal environments.}, } @article {pmid30450831, year = {2018}, author = {Wackett, LP}, title = {Diverse final electron acceptors: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4194-4195}, doi = {10.1111/1462-2920.14464}, pmid = {30450831}, issn = {1462-2920}, } @article {pmid30450830, year = {2018}, author = {}, title = {A subunit of the HOPS endocytic tethering complex, FgVps41, is important for fungal development and plant infection in Fusarium graminearum.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4196}, doi = {10.1111/1462-2920.14460}, pmid = {30450830}, issn = {1462-2920}, } @article {pmid30450829, year = {2018}, author = {Kingsley, RA and Langridge, G and Smith, SE and Makendi, C and Fookes, M and Wileman, TM and El Ghany, MA and Keith Turner, A and Dyson, ZA and Sridhar, S and Pickard, D and Kay, S and Feasey, N and Wong, V and Barquist, L and Dougan, G}, title = {Functional analysis of Salmonella Typhi adaptation to survival in water.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4079-4090}, pmid = {30450829}, issn = {1462-2920}, support = {BB/R012504/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Wellcome Trust/ ; }, abstract = {Contaminated water is a major risk factor associated with the transmission of Salmonella enterica serovar Typhi (S. Typhi), the aetiological agent of human typhoid. However, little is known about how this pathogen adapts to living in the aqueous environment. We used transcriptome analysis (RNA-seq) and transposon mutagenesis (TraDIS) to characterize these adaptive changes and identify multiple genes that contribute to survival. Over half of the genes in the S. Typhi genome altered expression level within the first 24 h following transfer from broth culture to water, although relatively few did so in the first 30 min. Genes linked to central metabolism, stress associated with arrested proton motive force and respiratory chain factors changed expression levels. Additionally, motility and chemotaxis genes increased expression, consistent with a scavenging lifestyle. The viaB-associated gene tviC encoding a glcNAc epimerase that is required for Vi polysaccharide biosynthesis was, along with several other genes, shown to contribute to survival in water. Thus, we define regulatory adaptation operating in S. Typhi that facilitates survival in water.}, } @article {pmid30450723, year = {2018}, author = {Prazeres, M and Renema, W}, title = {Evolutionary significance of the microbial assemblages of large benthic Foraminifera.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12482}, pmid = {30450723}, issn = {1469-185X}, support = {//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NWO)/ ; }, abstract = {Large benthic Foraminifera (LBF) are major carbonate producers on coral reefs, and are hosts to a diverse symbiotic microbial community. During warm episodes in the geological past, these reef-building organisms expanded their geographical ranges as subtropical and tropical belts moved into higher latitudes. During these range-expansion periods, LBF were the most prolific carbonate producers on reefs, dominating shallow carbonate platforms over reef-building corals. Even though the fossil and modern distributions of groups of species that harbour different types of symbionts are known, the nature, mechanisms, and factors that influence their occurrence remain elusive. Furthermore, the presence of a diverse and persistent bacterial community has only recently gained attention. We examined recent advances in molecular identification of prokaryotic (i.e. bacteria) and eukaryotic (i.e. microalgae) associates, and palaeoecology, and place the partnership with bacteria and algae in the context of climate change. In critically reviewing the available fossil and modern data on symbiosis, we reveal a crucial role of microalgae in the response of LBF to ocean warming, and their capacity to colonise a variety of habitats, across both latitudes and broad depth ranges. Symbiont identity is a key factor enabling LBF to expand their geographic ranges when the sea-surface temperature increases. Our analyses showed that over the past 66 million years (My), diatom-bearing species were dominant in reef environments. The modern record shows that these species display a stable, persistent eukaryotic assemblage across their geographic distribution range, and are less dependent on symbiotic photosynthesis for survival. By contrast, dinoflagellate and chlorophytic species, which show a provincial distribution, tend to have a more flexible eukaryotic community throughout their range. This group is more dependent on their symbionts, and flexibility in their symbiosis is likely to be the driving force behind their evolutionary history, as they form a monophyletic group originating from a rhodophyte-bearing ancestor. The study of bacterial assemblages, while still in its infancy, is a promising field of study. Bacterial communities are likely to be shaped by the local environment, although a core bacterial microbiome is found in species with global distributions. Cryptic speciation is also an important factor that must be taken into consideration. As global warming intensifies, genetic divergence in hosts in addition to the range of flexibility/specificity within host-symbiont associations will be important elements in the continued evolutionary success of LBF species in a wide range of environments. Based on fossil and modern data, we conclude that the microbiome, which includes both algal and bacterial partners, is a key factor influencing the evolution of LBF. As a result, the microbiome assists LBF in colonising a wide range of habitats, and allowed them to become the most important calcifiers on shallow platforms worldwide during periods of ocean warming in the geologic past. Since LBF are crucial ecosystem engineers and prolific carbonate producers, the microbiome is a critical component that will play a central role in the responses of LBF to a changing ocean, and ultimately in shaping the future of coral reefs.}, } @article {pmid30450650, year = {2018}, author = {Schack, CR and Gordon, DP and Ryan, KG}, title = {Modularity is the mother of invention: a review of polymorphism in bryozoans.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12478}, pmid = {30450650}, issn = {1469-185X}, support = {80837//VUW/ ; }, abstract = {Modularity is a fundamental concept in biology. Most taxa within the colonial invertebrate phylum Bryozoa have achieved division of labour through the development of specialized modules (polymorphs), and this group is perhaps the most outstanding exemplar of the phenomenon. We provide a comprehensive description of the diversity, morphology and function of these polymorphs and the significance of modularity to the evolutionary success of the phylum, which has >21000 described fossil and living species. Modular diversity likely arose from heterogeneous microenvironmental conditions, and cormidia (repeated clusters of associated modules) are an emergent property of the cue thresholds governing zooid plasticity. Polymorphs in a colony have, during phylogeny, transitioned into associated non-zooidal structures (appendages), increasing colonial integration. While the level of module compartmentalization is important for the evolution of bryozoan polymorphism, it may be less influential for other colonial invertebrates.}, } @article {pmid30449717, year = {2019}, author = {Xu, L and Zhao, J and Liu, M and Kurath, G and Breyta, RB and Ren, G and Yin, J and Liu, H and Lu, T}, title = {Phylogeography and evolution of infectious hematopoietic necrosis virus in China.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {19-28}, doi = {10.1016/j.ympev.2018.10.030}, pmid = {30449717}, issn = {1095-9513}, abstract = {Infectious hematopoietic necrosis virus (IHNV) is a well-known rhabdoviral pathogen of salmonid fish. In this study, a comprehensive analysis of 40 IHNV viruses isolated from thirteen fish farms in nine geographically dispersed Chinese provinces during 2012 to 2017 is presented. Identity of nucleotide and amino acid sequences among all the complete glycoprotein (G) genes from Chinese isolates was 98.0-100% and 96.7-100%, respectively. Coalescent phylogenetic analyses revealed that all the Chinese IHN virus characterized in this study were in a monophyletic clade that had a most recent common ancestor with the J Nagano (JN) subgroup within the J genogroup of IHNV. Within the Chinese IHNV clade isolates obtained over successive years from the same salmon fish farm clustered in strongly supported subclades, suggesting maintenance and diversification of virus over time within individual farms. There was also evidence for regional virus transmission within provinces, and some cases of longer distance transmission between distant provinces, such as Gansu and Yunnan. The data demonstrated that IHNV has evolved into a new subgroup in salmon farm environments in China, and IHNV isolates are undergoing molecular evolution within fish farms. We suggest that Chinese IHNV comprises a separate JC subgroup within the J genogroup of IHNV.}, } @article {pmid30449304, year = {2018}, author = {Gaston, KJ and Soga, M and Duffy, JP and Garrett, JK and Gaston, S and Cox, DTC}, title = {Personalised Ecology.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {916-925}, doi = {10.1016/j.tree.2018.09.012}, pmid = {30449304}, issn = {1872-8383}, abstract = {The field of ecology has focused on understanding characteristics of natural systems in a manner as free as possible from biases of human observers. However, demand is growing for knowledge of human-nature interactions at the level of individual people. This is particularly driven by concerns around human health consequences due to changes in positive and negative interactions. This requires attention to the biased ways in which people encounter and experience other organisms. Here we define such a 'personalised ecology', and discuss its connections to other aspects of the field. We propose a framework of focal research topics, shaped by whether the unit of analysis is a single person, a single population, or multiple populations, and whether a human or nature perspective is foremost.}, } @article {pmid30449037, year = {2018}, author = {Edme, A and Zobač, P and Korsten, P and Albrecht, T and Schmoll, T and Krist, M}, title = {Moderate heritability and low evolvability of sperm morphology in a species with high risk of sperm competition, the collared flycatcher Ficedula albicollis.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13404}, pmid = {30449037}, issn = {1420-9101}, support = {P506/12/2472//Czech Republic/ ; //German Research Foundation (DFG)/ ; IGA_PrF_2018_016//IGA UPOL/ ; }, abstract = {Spermatozoa represent the morphologically most diverse type of animal cells and show remarkable variation in size across and also within species. To understand the evolution of this diversity, it is important to reveal to what degree this variation is genetic or environmental in origin and whether this depends on species' life histories. Here we applied quantitative genetic methods to a pedigreed multigenerational data set of the collared flycatcher Ficedula albicollis, a passerine bird with high levels of extra-pair paternity, to partition genetic and environmental sources of phenotypic variation in sperm dimensions for the first time in a natural population. Narrow-sense heritability (h2) of total sperm length amounted to 0.44 ± 0.14 SE, whereas the corresponding figure for evolvability (estimated as coefficient of additive genetic variation, CVa) was 0.02 ± 0.003 SE. We also found an increase in total sperm length within individual males between the arrival and nestling period. This seasonal variation may reflect constraints in the production of fully elongated spermatozoa shortly after arrival at the breeding grounds. There was no evidence of an effect of male age on sperm dimensions. In many previous studies on laboratory populations of several insect, mammal and avian species, heritabilities of sperm morphology were higher, whereas evolvabilities were similar. Explanations for the differences in heritability may include variation in the environment (laboratory vs. wild), intensity of sexual selection via sperm competition (high vs. low) and genetic architecture that involves unusual linkage disequilibrium coupled with overdominance in one of the studied species.}, } @article {pmid30448962, year = {2018}, author = {Gmiter, D and Czerwonka, G and Drewnowska, JM and Swiecicka, I and Kaca, W}, title = {Draft Genome Sequences of Proteus mirabilis K1609 and K670: A Model Strains for Territoriality Examination.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1598-6}, pmid = {30448962}, issn = {1432-0991}, support = {8636/E-342/SPUB/2016/2//Specific Scientific Equipment Programme/ ; POPW.01.03.00-20-034/09-00//Operational Program Development of Eastern Poland 2007-2013/ ; 612 529//BS UJK/ ; }, abstract = {Proteus mirabilis is a pathogenic Gram-negative bacterium characterized by its ability to swarm across surfaces, which frequently leads to colonization of the urinary tract and causes severe infections. P. mirabilis strains are also well known from their self-recognition phenomenon, referred to as Dienes phenomenon. In this study, we present novel aspect of self-recognition, which is a hierarchy in terms of strains territoriality. We report the draft genome sequences of P. mirabilis K1609 and K670 strains exhibiting the strongest and the weakest territoriality, respectively. Our results indicated that K1609 is closely related to strain BB2000, a model system for self-recognition, comparing with the K670. We annotated genes associated with recognition of kin and swarming initiation control and indicated polymorphisms by which observed differences in territoriality might results from. The phenotypic and genomic features of both strains reveal their application as a model organisms for studying not only the mechanisms of kin-recognition but also strains territoriality, thus providing new approach to the phenomenon. Availability of these genome sequences may facilitate understanding of the interactions between P. mirabilis strains.}, } @article {pmid30448771, year = {2018}, author = {Qi, Y and Dong, C}, title = {Incorrect policy interpretation affects conclusion on SO2 emissions by coal-fired power plants in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11429}, doi = {10.1073/pnas.1814665115}, pmid = {30448771}, issn = {1091-6490}, } @article {pmid30448440, year = {2019}, author = {Jena, MK and Jaswal, S and Kumar, S and Mohanty, AK}, title = {Molecular mechanism of mammary gland involution: An update.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {145-155}, doi = {10.1016/j.ydbio.2018.11.002}, pmid = {30448440}, issn = {1095-564X}, abstract = {The mammary gland (MG) is a unique organ responsible for milk synthesis, secretion, and involution to prepare the gland for subsequent lactation. The mammary epithelial cells (MECs), which are the milk synthesizing units of the MG, proliferate, differentiate, undergo apoptosis and regenerate following a cyclic pathway of lactation - involution - lactation, fine-tuning these molecular events through hormones, growth factors and other regulatory molecules. The developmental stages of the MG are embryonic, prepubertal, pubertal, pregnancy, lactation and involution, with major developmental processes occurring after puberty. The involution stage includes interesting physiological processes such as MEC apoptosis, matrix remodeling, and the generation of cells regaining the shape of a virgin MG. Signal transducer and activator of transcription 3 (STAT3) is the established master regulator of this process and aberrant expression of STAT3 leads to subnormal involution and may induce neoplasia. Several studies have reported on the molecular mechanism of MG involution with substantial knowledge being gained about this process; however, a deep understanding of this phenomenon has yet to be attained. This review focuses deeply on the molecular details of post-lactational regression, the signaling pathways involved in the lactation-involution cycle, and the latest developments in STAT3-associated MG neoplasia. Deep insight into the involution process will pave the way towards understanding the biology, apoptosis, and oncogenesis of the MG.}, } @article {pmid30448439, year = {2019}, author = {Simkin, JE and Zhang, D and Stamp, LA and Newgreen, DF}, title = {Fine scale differences within the vagal neural crest for enteric nervous system formation.}, journal = {Developmental biology}, volume = {446}, number = {1}, pages = {22-33}, doi = {10.1016/j.ydbio.2018.11.007}, pmid = {30448439}, issn = {1095-564X}, abstract = {The enteric nervous system is mostly derived from vagal neural crest (NC) cells adjacent to somites (s)1-7. We used in ovo focal fluorescent vital dyes and focal electroporation of fluorophore-encoding plasmids in quail embryos to investigate NC cell migration to the foregut initially and later throughout the entire gut. NC cells of different somite-level origins were largely separate until reaching the foregut at about QE2.5, when all routes converged. By QE3.5, NC cells of different somite-levels became mixed, although s1-s2 NC cells were mainly confined to rostral foregut. Mid-vagal NC-derived cells (s3 and s4 level) arrived earliest at the foregut, and occurred in greatest number. By QE6.5 ENS was present from foregut to hindgut. Mid-vagal NC-derived cells occurred in greatest numbers from foregut to distal hindgut. NC-derived cells of s2, s5, and s6 levels were fewer and were widely distributed but were never observed in the distal hindgut. Rostro-vagal (s1) and caudo-vagal (s7) levels were few and restricted to the foregut. Single somite levels of quail neural tube/NC from s1 to s8 were combined with chick aneural ChE4.5 midgut and hindgut and the ensemble was grown on the chorio-allantoic membrane for 6 days. This tests ENS-forming competence in the absence of intra-segmental competition between NC cells, of differential influences of segmental paraxial tissues, and of positional advantage. All vagal NC-levels, but not s8 level, furnished enteric plexuses in the recipient gut, but the density of both ENS cells in total and neurons was highest from mid-vagal level donors, as was the length colonised. We conclude that the fate and competence for ENS formation of vagal NC sub-levels is not uniform over the vagal level but is biased to favour mid-vagal levels. Overviewing this and prior studies suggests the vagal region is, as in its traditional sense, a natural unit but with complex sub-divisions.}, } @article {pmid30448198, year = {2018}, author = {Prasetyoputri, A and Jarrad, AM and Cooper, MA and Blaskovich, MAT}, title = {The Eagle Effect and Antibiotic-Induced Persistence: Two Sides of the Same Coin?.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.10.007}, pmid = {30448198}, issn = {1878-4380}, abstract = {The Eagle effect describes a phenomenon in which bacteria or fungi exposed to concentrations of antibiotic higher than an optimal bactericidal concentration (OBC) have paradoxically improved levels of survival than at the OBC due to a decreased net rate of cell death. Despite extensive observational reports of this effect in different microorganisms, its underlying mode of action is not well understood. Although aspects of the Eagle effect resemble persistence, there is strong evidence that these phenomena are substantially different phenotypic responses to antibiotic treatment. We present an overview of the microorganism and antimicrobial combinations in which the Eagle effect has been observed. Proposed underlying mechanism(s) are assessed, and the Eagle effect and microbial persistence are compared and contrasted. The clinical relevance of the Eagle effect is reviewed, incorporating evidence from experimental in vitro and in vivo studies, as well as clinical reports.}, } @article {pmid30447939, year = {2019}, author = {Gillson, L and Biggs, H and Smit, IPJ and Virah-Sawmy, M and Rogers, K}, title = {Finding Common Ground between Adaptive Management and Evidence-Based Approaches to Biodiversity Conservation.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {31-44}, doi = {10.1016/j.tree.2018.10.003}, pmid = {30447939}, issn = {1872-8383}, abstract = {Adaptive management (AM) and evidence-based conservation (EBC) have emerged as major decision-making frameworks for conservation management. AM deals with complexity and the importance of local context in making conservation decisions under conditions of high variability, uncertainty, and rapid environmental and social change. EBC seeks for generality from empirical data and aims to develop and enhance best practice. The goal of this review is to explore opportunities for finding common ground between AM and EBC. We propose a framework for distinguishing the subset of conservation problems that are amenable to an evidence-based approach, based on levels of uncertainty, complexity, and social agreement. We then suggest ways for combining multiple lines of evidence and developing greater opportunities for iteration and co-learning in EBC.}, } @article {pmid30447938, year = {2018}, author = {Fajardo, A and McIntire, EJB and Olson, ME}, title = {When Short Stature Is an Asset in Trees.}, journal = {Trends in ecology & evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tree.2018.10.011}, pmid = {30447938}, issn = {1872-8383}, abstract = {With their imposing grandeur, the small number of very tall tree species attract a disproportionate amount of scientific study. We right this bias by focusing here on the shorter trees, which often grow in the shade of the giants and many other places besides. That tall trees are so restricted in distribution indicates that there are far more habitats available for small trees. We discuss some leading candidates for the mechanisms that limit maximum plant height in any given habitat, as well as why every habitat has a range of plant sizes. At least two attributes - greater adaptation capacity and higher drought resistance - suggest that the forests of the future belong to short trees.}, } @article {pmid30447257, year = {2018}, author = {Li, R and Helbig, L and Fu, J and Bian, X and Herrmann, J and Baumann, M and Stewart, AF and Müller, R and Li, A and Zips, D and Zhang, Y}, title = {Expressing cytotoxic compounds in Escherichia coli Nissle 1917 for tumor-targeting therapy.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.11.001}, pmid = {30447257}, issn = {1769-7123}, abstract = {Abnormal blood vessels and hypoxic and necrotic regions are common features of solid tumors and related to the malignant phenotype and therapy resistance. Certain obligate or facultative anaerobic bacteria exhibit inherent ability to colonize and proliferate within solid tumors in vivo. Escherichia coli Nissle 1917 (EcN), a non-pathogenic probiotic in European markets, has been known to proliferate selectively in the interface between the viable and necrotic regions of solid tumors. The objective of this study was to establish a tumor-targeting therapy system using the genetically engineered EcN for targeted delivery of cytotoxic compounds, including colibactin, glidobactin and luminmide. Biosynthetic gene clusters of these cytotoxic compounds were introduced into EcN and the corresponding compounds were detected in the resultant recombinant EcN strains. The recombinant EcN showed significant cytotoxic activity in vitro and in vivo as well, and significantly suppressed the tumor growth. Together, this study confirmed efficient tumor-targeting colonization of EcN and demonstrated its potentiality in the tumor-specific delivery of cytotoxic compounds as a new tumor-targeting therapy system.}, } @article {pmid30447180, year = {2019}, author = {Kelu, JJ and Webb, SE and Galione, A and Miller, AL}, title = {Characterization of ADP-ribosyl cyclase 1-like (ARC1-like) activity and NAADP signaling during slow muscle cell development in zebrafish embryos.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {211-225}, doi = {10.1016/j.ydbio.2018.11.005}, pmid = {30447180}, issn = {1095-564X}, abstract = {We recently demonstrated the requirement of two-pore channel type 2 (TPC2)-mediated Ca2+ release during slow muscle cell differentiation and motor circuit maturation in intact zebrafish embryos. However, the upstream trigger(s) of TPC2/Ca2+ signaling during these developmental processes remains unclear. Nicotinic acid adenine dinucleotide phosphate (NAADP) is a potent Ca2+ mobilizing messenger, which is suggested to target TPC2 in mediating the release of Ca2+ from acidic vesicles. Here, we report the molecular cloning of the zebrafish ADP ribosyl cyclase (ARC) homolog (i.e., ARC1-like), which is a putative enzyme for generating NAADP. We characterized the expression of the arc1-like transcript and the NAADP levels between ~ 16 h post-fertilization (hpf) and ~ 48 hpf in whole zebrafish embryos. We showed that if ARC1-like (when fused with either EGFP or tdTomato) was overexpressed it localized in the plasma membrane, and associated with intracellular organelles, such as the acidic vesicles, Golgi complex and sarcoplasmic reticulum, in primary muscle cell cultures. Morpholino (MO)-mediated knockdown of arc1-like or pharmacological inhibition of ARC1-like (via treatment with nicotinamide), led to an attenuation of Ca2+ signaling and disruption of slow muscle cell development. In addition, the injection of arc1-like mRNA into ARC1-like morphants partially rescued the Ca2+ signals and slow muscle cell development. Together, our data might suggest a link between ARC1-like, NAADP, TPC2 and Ca2+ signaling during zebrafish myogenesis.}, } @article {pmid30446824, year = {2018}, author = {Morris, VB and Kable, E and Koop, D and Cisternas, P and Byrne, M}, title = {Early development of the feeding larva of the sea urchin Heliocidaris tuberculata: role of the small micromeres.}, journal = {Development genes and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00427-018-0622-y}, pmid = {30446824}, issn = {1432-041X}, abstract = {The two modes of development in sea urchins are direct development, in which the adult develops directly from the gastrula to the adult and does not feed, and indirect development, in which the adult develops indirectly through a feeding larva. In this account of the indirect, feeding larva of Heliocidaris tuberculata, the question raised is whether an evolutionary difference of unequal cell divisions contributes to the development of feeding structures in the indirect larva. In indirect development, the cell divisions at the fourth and fifth cell cycles of the zygote are unequal, with four small micromeres formed at the vegetal pole at the fifth cell division. In direct development, these cell divisions are not unequal. From their position at the head of the archenteron, the small micromeres are strategically located to contribute to the feeding tissues of the larva and the adult of H. tuberculata.}, } @article {pmid30446787, year = {2019}, author = {Ten, LN and Li, W and Lee, SY and Kang, IK and Cho, YJ and Kim, MK and Jung, HY}, title = {Hymenobacter pomorum sp. nov., Isolated from Apple Orchard Soil.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {117-123}, doi = {10.1007/s00284-018-1595-9}, pmid = {30446787}, issn = {1432-0991}, support = {2018H1D3A2065415//National Research Foundation of Korea/ ; }, abstract = {A Gram-stain-negative, non-motile, rod-shaped bacterial strain, designated 9-2-1-1T, was isolated from apple orchard soil in Daegu, Republic of Korea. Comparative 16S rRNA gene sequence analysis showed that the isolate belongs to the family Cytophagaceae, Bacteroidetes and it is most closely related to Hymenobacter metalli A2-91T (97.8% similarity) and Hymenobacter marinus KJ035T (96.6%). Growth of strain 9-2-1-1T was observed at 4-30 °C, pH 6-8, and in the presence of 0-1.0% NaCl. The G+C content of the genomic DNA was 62.0 mol%. The predominant respiratory quinone of the isolate was MK-7; the major fatty acids were C15:0 iso (29.3%), C16:1ω5c (15.4%), C15:0 anteiso (12.5%), summed feature 3 (C16:1ω7c/C16:1ω6c; 12.3%), and C16:0 (10.6%); and the major polar lipid was phosphatidylethanolamine. The phenotypic and chemotaxonomic data supported the affiliation of strain 9-2-1-1T with the genus Hymenobacter. However, the DNA-DNA relatedness between the isolate and H. metalli and H. marinus were 31.3% and 24.7%, respectively. The DNA-DNA hybridization result and the differentiating phenotypic properties clearly indicate that strain 9-2-1-1T is the representative of a novel species in the genus Hymenobacter, for which the name Hymenobacter pomorum sp. nov. is proposed. The type strain is 9-2-1-1T (=KCTC 52740T = JCM 32193T).}, } @article {pmid30446725, year = {2018}, author = {Baker, J}, title = {The Doctor Who theme and beyond: female pioneers of electronic music.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {470-471}, doi = {10.1038/d41586-018-07439-1}, pmid = {30446725}, issn = {1476-4687}, } @article {pmid30446724, year = {2018}, author = {Koch, C}, title = {Paul G. Allen (1953-2018).}, journal = {Nature}, volume = {563}, number = {7732}, pages = {474}, doi = {10.1038/d41586-018-07259-3}, pmid = {30446724}, issn = {1476-4687}, } @article {pmid30446618, year = {2018}, author = {Yan, X and Akiyama, H}, title = {Overestimation of N2O mitigation potential by water management in rice paddy fields.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11204-E11205}, pmid = {30446618}, issn = {1091-6490}, mesh = {Agriculture ; Climate ; *Nitrous Oxide ; *Oryza ; Water ; }, } @article {pmid30446617, year = {2018}, author = {Kritee, K and Rudek, J and Hamburg, SP and Adhya, TK and Loecke, T and Ahuja, R}, title = {Reply to Yan and Akiyama: Nitrous oxide emissions from rice and their mitigation potential depend on the nature of intermittent flooding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11206-E11207}, pmid = {30446617}, issn = {1091-6490}, mesh = {Climate ; Floods ; *Nitrous Oxide ; *Oryza ; Water ; }, } @article {pmid30446616, year = {2018}, author = {Einsle, JF and Eggeman, AS and Martineau, BH and Saghi, Z and Collins, SM and Blukis, R and Bagot, PAJ and Midgley, PA and Harrison, RJ}, title = {Nanomagnetic properties of the meteorite cloudy zone.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11436-E11445}, doi = {10.1073/pnas.1809378115}, pmid = {30446616}, issn = {1091-6490}, abstract = {Meteorites contain a record of their thermal and magnetic history, written in the intergrowths of iron-rich and nickel-rich phases that formed during slow cooling. Of intense interest from a magnetic perspective is the "cloudy zone," a nanoscale intergrowth containing tetrataenite-a naturally occurring hard ferromagnetic mineral that has potential applications as a sustainable alternative to rare-earth permanent magnets. Here we use a combination of high-resolution electron diffraction, electron tomography, atom probe tomography (APT), and micromagnetic simulations to reveal the 3D architecture of the cloudy zone with subnanometer spatial resolution and model the mechanism of remanence acquisition during slow cooling on the meteorite parent body. Isolated islands of tetrataenite are embedded in a matrix of an ordered superstructure. The islands are arranged in clusters of three crystallographic variants, which control how magnetic information is encoded into the nanostructure. The cloudy zone acquires paleomagnetic remanence via a sequence of magnetic domain state transformations (vortex to two domain to single domain), driven by Fe-Ni ordering at 320 °C. Rather than remanence being recorded at different times at different positions throughout the cloudy zone, each subregion of the cloudy zone records a coherent snapshot of the magnetic field that was present at 320 °C. Only the coarse and intermediate regions of the cloudy zone are found to be suitable for paleomagnetic applications. The fine regions, on the other hand, have properties similar to those of rare-earth permanent magnets, providing potential routes to synthetic tetrataenite-based magnetic materials.}, } @article {pmid30446615, year = {2018}, author = {Romney, ALT and Davis, EM and Corona, MM and Wagner, JT and Podrabsky, JE}, title = {Temperature-dependent vitamin D signaling regulates developmental trajectory associated with diapause in an annual killifish.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12763-12768}, doi = {10.1073/pnas.1804590115}, pmid = {30446615}, issn = {1091-6490}, mesh = {Animals ; Caenorhabditis elegans/metabolism ; Cholestenes/metabolism ; Dehydrocholesterols/metabolism ; Diapause/*physiology ; Drosophila/metabolism ; Ecdysone/metabolism ; Fundulidae/*metabolism ; Receptors, Calcitriol/metabolism ; Signal Transduction/*physiology ; Temperature ; Vitamin D/analogs & derivatives/*metabolism ; }, abstract = {The mechanisms that integrate environmental signals into developmental programs remain largely uncharacterized. Nuclear receptors (NRs) are ligand-regulated transcription factors that orchestrate the expression of complex phenotypes. The vitamin D receptor (VDR) is an NR activated by 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3], a hormone derived from 7-dehydrocholesterol (7-DHC). VDR signaling is best known for regulating calcium homeostasis in mammals, but recent evidence suggests a diversity of uncharacterized roles. In response to incubation temperature, embryos of the annual killifish Austrofundulus limnaeus can develop along two alternative trajectories: active development and diapause. These trajectories diverge early in development, from a biochemical, morphological, and physiological perspective. We manipulated incubation temperature to induce the two trajectories and profiled changes in gene expression using RNA sequencing and weighted gene coexpression network analysis. We report that transcripts involved in 1,25(OH)2D3 synthesis and signaling are expressed in a trajectory-specific manner. Furthermore, exposure of embryos to vitamin D3 analogs and Δ4-dafachronic acid directs continuous development under diapause-inducing conditions. Conversely, blocking synthesis of 1,25(OH)2D3 induces diapause in A. limnaeus and a diapause-like state in zebrafish, suggesting vitamin D signaling is critical for normal vertebrate development. These data support vitamin D signaling as a molecular pathway that can regulate developmental trajectory and metabolic dormancy in a vertebrate. Interestingly, the VDR is homologous to the daf-12 and ecdysone NRs that regulate dormancy in Caenorhabditis elegans and Drosophila We suggest that 7-DHC-derived hormones and their associated NRs represent a conserved pathway for the integration of environmental information into developmental programs associated with life history transitions in animals.}, } @article {pmid30446614, year = {2018}, author = {Wang, Q and Li, Y and Ishikawa, K and Kosami, KI and Uno, K and Nagawa, S and Tan, L and Du, J and Shimamoto, K and Kawano, Y}, title = {Resistance protein Pit interacts with the GEF OsSPK1 to activate OsRac1 and trigger rice immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11551-E11560}, doi = {10.1073/pnas.1813058115}, pmid = {30446614}, issn = {1091-6490}, abstract = {Resistance (R) genes encode intracellular nucleotide-binding/leucine-rich repeat-containing (NLR) family proteins that serve as critical plant immune receptors to induce effector-triggered immunity (ETI). NLR proteins possess a tripartite domain architecture consisting of an N-terminal variable region, a central nucleotide-binding domain, and a C-terminal leucine-rich repeat. N-terminal coiled-coil (CC) or Toll-interleukin 1 receptor (TIR) domains of R proteins appear to serve as platforms to trigger immune responses, because overexpression of the CC or TIR domain of some R proteins is sufficient to induce an immune response. Because direct downstream signaling molecules of R proteins remain obscure, the molecular mechanisms by which R proteins regulate downstream signaling are largely unknown. We reported previously that a rice R protein named Pit triggers ETI through a small GTPase, OsRac1, although how Pit activates OsRac1 is unclear. Here, we identified OsSPK1, a DOCK family guanine nucleotide exchange factor, as an interactor of Pit and activator for OsRac1. OsSPK1 contributes to signaling by two disease-resistance genes, Pit and Pia, against the rice blast fungus Magnaporthe oryzae and facilitates OsRac1 activation in vitro and in vivo. The CC domain of Pit is required for its binding to OsSPK1, OsRac1 activation, and the induction of cell death. Overall, we conclude that OsSPK1 is a direct and key signaling target of Pit-mediated immunity. Our results shed light on how R proteins trigger ETI through direct downstream molecules.}, } @article {pmid30446613, year = {2018}, author = {Cory, S}, title = {Phosphatidylserine hide-and-seek.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12092-12094}, pmid = {30446613}, issn = {1091-6490}, mesh = {Macrophages ; *Phosphatidylserines ; Phospholipids ; *Precursor Cells, B-Lymphoid ; }, } @article {pmid30446612, year = {2018}, author = {Ramsbottom, SA and Molinari, E and Srivastava, S and Silberman, F and Henry, C and Alkanderi, S and Devlin, LA and White, K and Steel, DH and Saunier, S and Miles, CG and Sayer, JA}, title = {Targeted exon skipping of a CEP290 mutation rescues Joubert syndrome phenotypes in vitro and in a murine model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12489-12494}, doi = {10.1073/pnas.1809432115}, pmid = {30446612}, issn = {1091-6490}, support = {MR/M012212/1//Medical Research Council/United Kingdom ; }, abstract = {Genetic treatments of renal ciliopathies leading to cystic kidney disease would provide a real advance in current therapies. Mutations in CEP290 underlie a ciliopathy called Joubert syndrome (JBTS). Human disease phenotypes include cerebral, retinal, and renal disease, which typically progresses to end stage renal failure (ESRF) within the first two decades of life. While currently incurable, there is often a period of years between diagnosis and ESRF that provides a potential window for therapeutic intervention. By studying patient biopsies, patient-derived kidney cells, and a mouse model, we identify abnormal elongation of primary cilia as a key pathophysiological feature of CEP290-associated JBTS and show that antisense oligonucleotide (ASO)-induced splicing of the mutated exon (41, G1890*) restores protein expression in patient cells. We demonstrate that ASO-induced splicing leading to exon skipping is tolerated, resulting in correct localization of CEP290 protein to the ciliary transition zone, and restoration of normal cilia length in patient kidney cells. Using a gene trap Cep290 mouse model of JBTS, we show that systemic ASO treatment can reduce the cystic burden of diseased kidneys in vivo. These findings indicate that ASO treatment may represent a promising therapeutic approach for kidney disease in CEP290-associated ciliopathy syndromes.}, } @article {pmid30446611, year = {2018}, author = {Coppock, A and Leeper, TJ and Mullinix, KJ}, title = {Generalizability of heterogeneous treatment effect estimates across samples.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12441-12446}, doi = {10.1073/pnas.1808083115}, pmid = {30446611}, issn = {1091-6490}, abstract = {The extent to which survey experiments conducted with nonrepresentative convenience samples are generalizable to target populations depends critically on the degree of treatment effect heterogeneity. Recent inquiries have found a strong correspondence between sample average treatment effects estimated in nationally representative experiments and in replication studies conducted with convenience samples. We consider here two possible explanations: low levels of effect heterogeneity or high levels of effect heterogeneity that are unrelated to selection into the convenience sample. We analyze subgroup conditional average treatment effects using 27 original-replication study pairs (encompassing 101,745 individual survey responses) to assess the extent to which subgroup effect estimates generalize. While there are exceptions, the overwhelming pattern that emerges is one of treatment effect homogeneity, providing a partial explanation for strong correspondence across both unconditional and conditional average treatment effect estimates.}, } @article {pmid30446610, year = {2018}, author = {Chouinard-Watkins, R and Bazinet, RP}, title = {ACSL6 is critical for maintaining brain DHA levels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12343-12345}, doi = {10.1073/pnas.1817557115}, pmid = {30446610}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {*Brain ; *Fatty Acids, Omega-3 ; }, } @article {pmid30446609, year = {2018}, author = {Camac, JS and Condit, R and FitzJohn, RG and McCalman, L and Steinberg, D and Westoby, M and Wright, SJ and Falster, DS}, title = {Partitioning mortality into growth-dependent and growth-independent hazards across 203 tropical tree species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12459-12464}, doi = {10.1073/pnas.1721040115}, pmid = {30446609}, issn = {1091-6490}, abstract = {Tree death drives population dynamics, nutrient cycling, and evolution within plant communities. Mortality variation across species is thought to be influenced by different factors relative to variation within species. The unified model provided here separates mortality rates into growth-dependent and growth-independent hazards. This model creates the opportunity to simultaneously estimate these hazards both across and within species. Moreover, it provides the ability to examine how species traits affect growth-dependent and growth-independent hazards. We derive this unified mortality model using cross-validated Bayesian methods coupled with mortality data collected over three census intervals for 203 tropical rainforest tree species at Barro Colorado Island (BCI), Panama. We found that growth-independent mortality tended to be higher in species with lower wood density, higher light requirements, and smaller maximum diameter at breast height (dbh). Mortality due to marginal carbon budget as measured by near-zero growth rate tended to be higher in species with lower wood density and higher light demand. The total mortality variation attributable to differences among species was large relative to variation explained by these traits, emphasizing that much remains to be understood. This additive hazards model strengthens our capacity to parse and understand individual-level mortality in highly diverse tropical forests and hence to predict its consequences.}, } @article {pmid30446608, year = {2018}, author = {Czajka, JJ and Abernathy, MH and Benites, VT and Baidoo, EEK and Deming, JW and Tang, YJ}, title = {Model metabolic strategy for heterotrophic bacteria in the cold ocean based on Colwellia psychrerythraea 34H.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12507-12512}, doi = {10.1073/pnas.1807804115}, pmid = {30446608}, issn = {1091-6490}, abstract = {Colwellia psychrerythraea 34H is a model psychrophilic bacterium found in the cold ocean-polar sediments, sea ice, and the deep sea. Although the genomes of such psychrophiles have been sequenced, their metabolic strategies at low temperature have not been quantified. We measured the metabolic fluxes and gene expression of 34H at 4 °C (the mean global-ocean temperature and a normal-growth temperature for 34H), making comparative analyses at room temperature (above its upper-growth temperature of 18 °C) and with mesophilic Escherichia coli When grown at 4 °C, 34H utilized multiple carbon substrates without catabolite repression or overflow byproducts; its anaplerotic pathways increased flux network flexibility and enabled CO2 fixation. In glucose-only medium, the Entner-Doudoroff (ED) pathway was the primary glycolytic route; in lactate-only medium, gluconeogenesis and the glyoxylate shunt became active. In comparison, E. coli, cold stressed at 4 °C, had rapid glycolytic fluxes but no biomass synthesis. At their respective normal-growth temperatures, intracellular concentrations of TCA cycle metabolites (α-ketoglutarate, succinate, malate) were 4-17 times higher in 34H than in E. coli, while levels of energy molecules (ATP, NADH, NADPH) were 10- to 100-fold lower. Experiments with E. coli mutants supported the thermodynamic advantage of the ED pathway at cold temperature. Heat-stressed 34H at room temperature (2 hours) revealed significant down-regulation of genes associated with glycolytic enzymes and flagella, while 24 hours at room temperature caused irreversible cellular damage. We suggest that marine heterotrophic bacteria in general may rely upon simplified metabolic strategies to overcome thermodynamic constraints and thrive in the cold ocean.}, } @article {pmid30446517, year = {2018}, author = {Karplus, VJ and Zhang, S and Almond, D}, title = {Reply to Qi and Dong: Policy clarification and robustness of effects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11430-E11431}, doi = {10.1073/pnas.1815003115}, pmid = {30446517}, issn = {1091-6490}, } @article {pmid30446409, year = {2019}, author = {Polishchuk, LV and Blanchard, JL}, title = {Uniting Discoveries of Abundance-Size Distributions from Soils and Seas.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {2-5}, doi = {10.1016/j.tree.2018.10.007}, pmid = {30446409}, issn = {1872-8383}, abstract = {Science is a search for patterns but there are few cross-habitat patterns in ecology. We propose key questions following the findings of consistent scaling of abundance versus body mass from bacteria to earthworms and whales, based on an almost forgotten study of soils and a well-known one from the open ocean.}, } @article {pmid30446408, year = {2019}, author = {Amodio, P and Boeckle, M and Schnell, AK and Ostojíc, L and Fiorito, G and Clayton, NS}, title = {Grow Smart and Die Young: Why Did Cephalopods Evolve Intelligence?.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {45-56}, doi = {10.1016/j.tree.2018.10.010}, pmid = {30446408}, issn = {1872-8383}, abstract = {Intelligence in large-brained vertebrates might have evolved through independent, yet similar processes based on comparable socioecological pressures and slow life histories. This convergent evolutionary route, however, cannot explain why cephalopods developed large brains and flexible behavioural repertoires: cephalopods have fast life histories and live in simple social environments. Here, we suggest that the loss of the external shell in cephalopods (i) caused a dramatic increase in predatory pressure, which in turn prevented the emergence of slow life histories, and (ii) allowed the exploitation of novel challenging niches, thus favouring the emergence of intelligence. By highlighting convergent and divergent aspects between cephalopods and large-brained vertebrates we illustrate how the evolution of intelligence might not be constrained to a single evolutionary route.}, } @article {pmid30446394, year = {2019}, author = {Fouet, C and Kamdem, C}, title = {Integrated Mosquito Management: Is Precision Control a Luxury or Necessity?.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {85-95}, doi = {10.1016/j.pt.2018.10.004}, pmid = {30446394}, issn = {1471-5007}, abstract = {The versatility of mosquito species that spread emerging arthropod-borne viruses such as Zika has highlighted the urgent need to re-evaluate mosquito-control standards. The prospect of using precise knowledge of the geographic distribution and vector status of local populations to guide targeted interventions has gained renewed attention, but the feasibility and utility of such an approach remain to be investigated. Using the example of mosquito management in the USA, we present ideas for designing, monitoring, and assessing precision vector control tailored to different environmental and epidemiological settings. We emphasize the technical adjustments that could be implemented in mosquito-control districts to enable targeted control while strengthening traditional management.}, } @article {pmid30446000, year = {2018}, author = {Kenmoe, S and Tagnouokam, PAN and Nde, CK and Mella-Tamko, GF and Njouom, R}, title = {Using dried blood spot for the detection of HBsAg and anti-HCV antibodies in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {818}, pmid = {30446000}, issn = {1756-0500}, support = {ANRS No 12289//Agence Nationale de Recherches sur le Sida et les Hépatites Virales (FR)/ ; }, abstract = {OBJECTIVE: Dried blood spots (DBS) offer multiple benefits for collecting, storing and shipping whole blood samples. Our objective was to compare, for the first time in Africa, the performance of DBS with respect to plasma in the detection of Hepatitis B surface antigen (HBsAg) and antibodies to Hepatitis C Virus (anti-HCV) using Architect, Abbott Diagnostics.

RESULTS: DBS had a sensitivity of 99%, a specificity of 100%, a positive predictive value of 99%, a negative predictive value of 100% and a kappa index of 0.99 for the detection of HBsAg. For anti-HCV detection, the sensitivity, specificity, positive predictive value, negative predictive value and kappa index were 99%, 98%, 98%, 99%, and 0.97, respectively. This study confirms that DBS may be a reliable alternative specimen type for HBV and HCV diagnosis.}, } @article {pmid30445997, year = {2018}, author = {Schmutz, C and Mäusezahl, D}, title = {The burden of gastroenteritis in Switzerland (BUGS) study: a research proposal for a 1-year, prospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {816}, pmid = {30445997}, issn = {1756-0500}, support = {15.030881//Bundesamt für Gesundheit/ ; 17.016481//Bundesamt für Gesundheit/ ; 4.17.02//Bundesamt für Lebensmittelsicherheit und Veterinärwesen/ ; }, abstract = {OBJECTIVES: Acute gastroenteritis (AG) is a usually self-limiting, but common disease worldwide. In Europe, incidence estimates range from 0.3-1.5 AG episodes/person-year. For Switzerland, available information on AG is restricted to notifiable foodborne diseases and findings from research studies starting at primary care level. The aims of this 1-year, population-based prospective cohort study are to assess the incidence, burden of disease, aetiology and socio-economic impact of AG in the Swiss general population. Additionally, the prevalence of bacterial gastrointestinal pathogens and bacteria harbouring antimicrobial resistances in the asymptomatic population shall be assessed.

RESULTS: Weekly follow-up of the cohort consisting of 3000 participants will provide incidence estimates of AG. Furthermore, information collected will be used to assess risk factors for experiencing an episode of AG, to explore determinants for help seeking, and to characterise the socio-economic impact of AG including absence from work and inability to perform daily activities. Aetiology of AG is determined by investigating stool samples from symptomatic participants. Finally, stool samples from participants collected during an asymptomatic period will be used to assess the prevalence of enterohaemorrhagic E. coli, Campylobacter spp., Salmonella spp. and Shigella spp. as well as of resistance to different antibiotics (extended-spectrum beta-lactamase-, fluoroquinolone- and carbapenemase-resistance).}, } @article {pmid30445994, year = {2018}, author = {Al Bahhawi, T and Doweri, AA and Sawadi, RM and Awaji, MY and Jarad, MM and Sulays, ZY and Madkor, KA}, title = {Consumption habits of pregnant women in the Jazan region, Saudi Arabia: a descriptive study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {817}, pmid = {30445994}, issn = {1756-0500}, abstract = {OBJECTIVE: Maternal nutritional habits are critical for the health of both mother and offspring. Postpartum outcomes for mother and infant are strongly influenced by the mother's nutritional status. Information about consumption habits among pregnant women in Saudi Arabia is scarce. Thus, this study aims to describe the consumption habits of pregnant women in the Jazan region, Saudi Arabia.

RESULTS: Meat, fish, and fruits were consumed by 97%, 86%, and 90% of the sample. Sugary desserts, fast food, and canned food were consumed by 90%, 81%, and 71% of the sample. Caffeine, juices, and milk were consumed by 75%, 92%, and 81% of the sample. Previous percentages show general higher consumption habits of food and beverages. Over-the-counter medication was used by only 17%. Folic acid, iron, and calcium use by 77%, 64%, and 58% of the sample, respectively. These percentage shows conservative use of Over-the-counter medication and sub-optimal use of important dietary supplements. Moreover, there was a positive association between caffeine intake and trimesters. Furthermore, there was negative association between education level and fish intake. Finally, canned foods consumption was higher among low income pregnant women.}, } @article {pmid30445991, year = {2018}, author = {Ayalew, TW and Nigatu, AM}, title = {Focused antenatal care utilization and associated factors in Debre Tabor Town, northwest Ethiopia, 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {819}, pmid = {30445991}, issn = {1756-0500}, abstract = {OBJECTIVE: Attending antenatal care helps to reduce the occurrence of maternal morbidity and mortality by providing chances for health promotion and information about danger signs, birth preparedness and where to seek care for pregnancy complications. Therefore identifying factors affecting the utilization of focused ANC service is of supreme importance.

RESULTS: A total of 317 mothers who had a history of antenatal care for their last birth during the previous 6 months were included in the study from which 112 (35.3%, 95% CI 30.6, 40.4) of mothers attended focused antenatal care services. Age of mother [AOR = 4.7, 95% CI 1.87, 11.88], Educational status [AOR = 2.5, 95% CI 1.00, 6.19], history of still birth [AOR = 13.1, 95% CI 2.14, 80.20] and planned pregnancy [AOR = 3.7, 95% CI 1.23, 11.12] were found to be major predictors for focused ANC service utilization. Proportion of focused antenatal care was low (35.3%). Age of mother, education, history of stillbirth and planned pregnancy were identified as predictors affecting focused antenatal care service utilization. Encouraging women's educational status, behavioral change communication at grass root level and improving the capacity and quality of ANC service are some of the recommendations forwarded.}, } @article {pmid30445921, year = {2018}, author = {Kondhare, KR and Malankar, NN and Devani, RS and Banerjee, AK}, title = {Genome-wide transcriptome analysis reveals small RNA profiles involved in early stages of stolon-to-tuber transitions in potato under photoperiodic conditions.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {284}, pmid = {30445921}, issn = {1471-2229}, support = {BT/PR8757/GET/119/5/2015//Department of Biotechnology , Ministry of Science and Technology/ ; }, mesh = {Gene Expression Profiling ; Genome, Plant/*genetics ; MicroRNAs/*genetics ; *Photoperiod ; Plant Stems/genetics/growth & development ; Plant Tubers/genetics/growth & development ; RNA, Plant/genetics ; RNA, Small Interfering/*genetics ; Solanum tuberosum/*genetics/growth & development ; }, abstract = {BACKGROUND: Small RNAs (sRNAs), especially miRNAs, act as crucial regulators of plant growth and development. Two other sRNA groups, trans-acting short-interfering RNAs (tasiRNAs) or phased siRNAs (phasiRNAs), are also emerging as potential regulators of plant development. Stolon-to-tuber transition in potato is an important developmental phase governed by many environmental, biochemical and hormonal cues. Among different environmental factors, photoperiod has a major influence on tuberization. Several mobile signals, mRNAs, proteins and transcription factors have been widely studied for their role in tuber formation in potato, however, no information is yet available that describes the molecular signals governing the early stages of stolon transitions or cell-fate changes at the stolon tip before it matures to potato. Stolon could be an interesting model for studying below ground organ development and we hypothesize that small RNAs might be involved in regulation of stolon-to-tuber transition process in potato. Also, there is no literature that describes the phased siRNAs in potato development.

RESULTS: We performed sRNA profiling of early stolon stages (4, 7 and 10 d) under long-day (LD; 16 h light, 8 h dark) and short-day (SD; 8 h light, 16 h dark) photoperiodic conditions. Altogether, 7 (out of 324) conserved and 12 (out of 311) novel miRNAs showed differential expression in early stolon stages under SD vs LD photoperiodic conditions. Key target genes (StGRAS, StTCP2/4 and StPTB6) exhibited differential expression in early stolon stages under SD vs LD photoperiodic conditions, indicative of their potential role in tuberization. Out of 830 TAS-like loci identified, 24 were cleaved by miRNAs to generate 190 phased siRNAs. Some of them targeted crucial tuberization genes such as StPTB1, POTH1 and StCDPKs. Two conserved TAS loci, referred as StTAS3 and StTAS5, which share close conservation with members of the Solanaceae family, were identified in our analysis. One TAS-like locus (StTm2) was validated for phased siRNA generation and one of its siRNA was predicted to cleave an important tuber marker gene StGA2ox1.

CONCLUSION: Our study suggests that sRNAs and their selective target genes could be associated with the regulation of early stages of stolon-to-tuber transitions in a photoperiod-dependent manner in potato.}, } @article {pmid30445920, year = {2018}, author = {Guo, DL and Li, Q and Lv, WQ and Zhang, GH and Yu, YH}, title = {MicroRNA profiling analysis of developing berries for 'Kyoho' and its early-ripening mutant during berry ripening.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {285}, pmid = {30445920}, issn = {1471-2229}, support = {31672106//National Natural Science Foundation of China/ ; U1504321//National Natural Science Foundation of China/ ; 194200510007//Zhongyuan Science and Technology Innovation Leaders/ ; }, mesh = {Fruit/*genetics/growth & development ; Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; Genome, Plant/*genetics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; RNA, Plant/*genetics ; Sequence Analysis, RNA ; Vitis/*genetics/growth & development ; }, abstract = {BACKGROUND: 'Fengzao' is an early-ripening bud mutant of 'Kyoho', which matures nearly 30 days earlier than 'Kyoho'. To gain a better understanding of the regulatory role of miRNAs in early-ripening of grape berry, high-throughput sequencing approach and quantitative RT-PCR validation were employed to identify miRNAs at the genome-wide level and profile the expression patterns of the miRNAs during berry development in 'Kyho' and 'Fengzao', respectively.

RESULTS: Nine independent small RNA libraries were constructed and sequenced in two varieties from key berry development stages. A total of 108 known miRNAs and 61 novel miRNAs were identified. Among that, 159 miRNAs identified in 'Fengzao' all completely expressed in 'Kyoho' and there were 10 miRNAs specifically expressed in 'Kyoho'. The expression profiles of known and novel miRNAs were quite similar between two varieties. As the major differentially expressed miRNAs, novel_144, vvi-miR3626-3p and vvi-miR3626-5p only expressed in 'Kyoho', vvi-miR399b and vvi-miR399e were down-regulated in 'Fengzao', while vvi-miR477b-3p up-regulated in 'Fengzao'. According to the expression analysis and previous reports, miR169-NF-Y subunit, miR398-CSD, miR3626-RNA helicase, miR399- phosphate transporter and miR477-GRAS transcription factor were selected as the candidates for further investigations of miRNA regulation role in the early-ripening of grape. The qRT-PCR analyses validated the contrasting expression patterns for these miRNAs and their target genes.

CONCLUSIONS: The miRNAome of the grape berry development of 'Kyoho', and its early-ripening bud mutant, 'Fengzao' were compared by high-throughput sequencing. The expression pattern of several key miRNAs and their target genes during grape berry development and ripening stages was examined. Our results provide valuable basis towards understanding the regulatory mechanisms of early-ripening of grape berry.}, } @article {pmid30445918, year = {2018}, author = {Wakita, Y and Shimomura, Y and Kitada, Y and Yamamoto, H and Ohashi, Y and Matsumoto, M}, title = {Taxonomic classification for microbiome analysis, which correlates well with the metabolite milieu of the gut.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {188}, pmid = {30445918}, issn = {1471-2180}, abstract = {BACKGROUND: 16S rRNA gene amplicon sequencing analysis (16S amplicon sequencing) has provided considerable information regarding the ecology of the intestinal microbiome. Recently, metabolomics has been used for investigating the crosstalk between the intestinal microbiome and the host via metabolites. In the present study, we determined the accuracy with which 16S rRNA gene data at different classification levels correspond to the metabolome data for an in-depth understanding of the intestinal environment.

RESULTS: Over 200 metabolites were identified using capillary electrophoresis and time-of-flight mass spectrometry (CE-TOFMS)-based metabolomics in the feces of antibiotic-treated and untreated mice. 16S amplicon sequencing, followed by principal component analysis (PCA) of the intestinal microbiome at each taxonomic rank, revealed differences between the antibiotic-treated and untreated groups in the first principal component in the family-, genus, and species-level analyses. These differences were similar to those observed in the PCA of the metabolome. Furthermore, a strong correlation between principal component (PC) scores of the metabolome and microbiome was observed in family-, genus-, and species-level analyses.

CONCLUSIONS: Lower taxonomic ranks such as family, genus, or species are preferable for 16S amplicon sequencing to investigate the correlation between the microbiome and metabolome. The correlation of PC scores between the microbiome and metabolome at lower taxonomic levels yield a simple method of integrating different "-omics" data, which provides insights regarding crosstalk between the intestinal microbiome and the host.}, } @article {pmid30445911, year = {2018}, author = {Garapati, HS and Mishra, K}, title = {Comparative genomics of nuclear envelope proteins.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {823}, pmid = {30445911}, issn = {1471-2164}, support = {BT BT/PR11752/BRB/10/685/2009//Department of Biotechnology , Ministry of Science and Technology/ ; SB/SO/BB-0045/2013//Science and Engineering Research Board/ ; }, abstract = {BACKGROUND: The nuclear envelope (NE) that encapsulates the nuclear genome is a double lipid bilayer with several integral and peripherally associated proteins. It is a characteristic feature of the eukaryotes and acts as a hub for a number of important nuclear events including transcription, repair, and regulated gene expression. The proteins associated with the nuclear envelope mediate the NE functions and maintain its structural integrity, which is crucial for survival. In spite of the importance of this structure, knowledge of the protein composition of the nuclear envelope and their function, are limited to very few organisms belonging to Opisthokonta and Archaeplastida supergroups. The NE composition is largely unknown in organisms outside these two supergroups.

RESULTS: In this study, we have taken a comparative sequence analysis approach to identify the NE proteome that is present across all five eukaryotic supergroups. We identified 22 proteins involved in various nuclear functions to be part of the core NE proteome. The presence of these proteins across eukaryotes, suggests that they are traceable to the Last Eukaryotic Common Ancestor (LECA). Additionally, we also identified the NE proteins that have evolved in a lineage specific manner and those that have been preserved only in a subset of organisms.

CONCLUSIONS: Our study identifies the conserved features of the nuclear envelope across eukaryotes and provides insights into the potential composition and the functionalities that were constituents of the LECA NE.}, } @article {pmid30445908, year = {2018}, author = {de Verdal, H and Vandeputte, M and Mekkawy, W and Chatain, B and Benzie, JAH}, title = {Quantifying the genetic parameters of feed efficiency in juvenile Nile tilapia Oreochromis niloticus.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {105}, pmid = {30445908}, issn = {1471-2156}, abstract = {BACKGROUND: Improving feed efficiency in fish is crucial at the economic, social and environmental levels with respect to developing a more sustainable aquaculture. The important contribution of genetic improvement to achieve this goal has been hampered by the lack of accurate basic information on the genetic parameters of feed efficiency in fish. We used video assessment of feed intake on individual fish reared in groups to estimate the genetic parameters of six growth traits, feed intake, feed conversion ratio (FCR) and residual feed intake in 40 pedigreed families of the GIFT strain of Nile tilapia, Oreochromis niloticus. Feed intake and growth were measured on juvenile fish (22.4 g mean body weight) during 13 consecutive meals, representing 7 days of measurements. We used these data to estimate the FCR response to different selection criteria to assess the potential of genetics as a means of increasing FCR in tilapia.

RESULTS: Our results demonstrate genetic control for FCR in tilapia, with a heritability estimate of 0.32 ± 0.11. Response to selection estimates showed FCR could be efficiently improved by selective breeding. Due to low genetic correlations, selection for growth traits would not improve FCR. However, weight loss at fasting has a high genetic correlation with FCR (0.80 ± 0.25) and a moderate heritability (0.23), and could be an easy to measure and efficient criterion to improve FCR by selective breeding in tilapia.

CONCLUSION: At this age, FCR is genetically determined in Nile tilapia. A selective breeding program could be possible and could help enabling the development of a more sustainable aquaculture production.}, } @article {pmid30445907, year = {2018}, author = {Jones, KE and Benitez, L and Angielczyk, KD and Pierce, SE}, title = {Adaptation and constraint in the evolution of the mammalian backbone.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {172}, pmid = {30445907}, issn = {1471-2148}, mesh = {*Adaptation, Physiological ; Anatomic Landmarks ; Animals ; *Biological Evolution ; Imaging, Three-Dimensional ; Locomotion ; Mammals/*anatomy & histology ; Phylogeny ; Principal Component Analysis ; Spine/*anatomy & histology ; }, abstract = {BACKGROUND: The axial skeleton consists of repeating units (vertebrae) that are integrated through their development and evolution. Unlike most tetrapods, vertebrae in the mammalian trunk are subdivided into distinct thoracic and lumbar modules, resulting in a system that is constrained in terms of count but highly variable in morphology. This study asks how thoracolumbar regionalization has impacted adaptation and evolvability across mammals. Using geometric morphometrics, we examine evolutionary patterns in five vertebral positions from diverse mammal species encompassing a broad range of locomotor ecologies. We quantitatively compare the effects of phylogenetic and allometric constraints, and ecological adaptation between regions, and examine their impact on evolvability (disparity and evolutionary rate) of serially-homologous vertebrae.

RESULTS: Although phylogenetic signal and allometry are evident throughout the trunk, the effect of locomotor ecology is partitioned between vertebral positions. Lumbar vertebral shape correlates most strongly with ecology, differentiating taxa based on their use of asymmetric gaits. Similarly, disparity and evolutionary rates are also elevated posteriorly, indicating a link between the lumbar region, locomotor adaptation, and evolvability.

CONCLUSION: Vertebral regionalization in mammals has facilitated rapid evolution of the posterior trunk in response to selection for locomotion and static body support.}, } @article {pmid30445906, year = {2018}, author = {Shen, Y and Kubben, N and Candia, J and Morozov, AV and Misteli, T and Losert, W}, title = {RefCell: multi-dimensional analysis of image-based high-throughput screens based on 'typical cells'.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {427}, pmid = {30445906}, issn = {1471-2105}, support = {Trans-NIH Center for Human Immunology (CHI), NIAID//National Institutes of Health/ ; FA9550-16-1-0052//Air Force Office of Scientific Research/ ; }, mesh = {High-Throughput Screening Assays/*methods ; Humans ; RNA, Small Interfering/*metabolism ; }, abstract = {BACKGROUND: Image-based high-throughput screening (HTS) reveals a high level of heterogeneity in single cells and multiple cellular states may be observed within a single population. Currently available high-dimensional analysis methods are successful in characterizing cellular heterogeneity, but suffer from the "curse of dimensionality" and non-standardized outputs.

RESULTS: Here we introduce RefCell, a multi-dimensional analysis pipeline for image-based HTS that reproducibly captures cells with typical combinations of features in reference states and uses these "typical cells" as a reference for classification and weighting of metrics. RefCell quantitatively assesses heterogeneous deviations from typical behavior for each analyzed perturbation or sample.

CONCLUSIONS: We apply RefCell to the analysis of data from a high-throughput imaging screen of a library of 320 ubiquitin-targeted siRNAs selected to gain insights into the mechanisms of premature aging (progeria). RefCell yields results comparable to a more complex clustering-based single-cell analysis method; both methods reveal more potential hits than a conventional analysis based on averages.}, } @article {pmid30445905, year = {2018}, author = {Tekle, YI and Wood, FC}, title = {A practical implementation of large transcriptomic data analysis to resolve cryptic species diversity problems in microbial eukaryotes.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {170}, pmid = {30445905}, issn = {1471-2148}, support = {R15 GM116103/GM/NIGMS NIH HHS/United States ; 1R15GM116103-01/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Biological Evolution ; DNA Barcoding, Taxonomic ; *Data Analysis ; Eukaryota/*genetics ; *Gene Expression Profiling ; Genetic Markers ; *Genetic Variation ; Genome ; Phylogeny ; Species Specificity ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Transcriptome sequencing has become a method of choice for evolutionary studies in microbial eukaryotes due to low cost and minimal sample requirements. Transcriptome data has been extensively used in phylogenomic studies to infer ancient evolutionary histories. However, its utility in studying cryptic species diversity is not well explored. An empirical investigation was conducted to test the applicability of transcriptome data in resolving two major types of discordances at lower taxonomic levels. These include cases where species have the same morphology but different genetics (cryptic species) and species of different morphologies but have the same genetics. We built a species comparison bioinformatic pipeline that takes into account the nature of transcriptome data in amoeboid microbes exemplifying such discordances.

RESULT: Our analyses of known or suspected cryptic species yielded consistent results regardless of the methods of culturing, RNA collection or sequencing. Over 95% of the single copy genes analyzed in samples of the same species sequenced using different methods and cryptic species had intra- and interspecific divergences below 2%. Only a minority of groups (2.91-4.87%) had high distances exceeding 2% in these taxa, which was likely caused by low data quality. This pattern was also observed in suspected genetically similar species with different morphologies. Transcriptome data consistently delineated all taxa above species level, including cryptically diverse species. Using our approach we were able to resolve cryptic species problems, uncover misidentification and discover new species. We also identified several potential barcode markers with varying evolutionary rates that can be used in lineages with different evolutionary histories.

CONCLUSION: Our findings demonstrate that transcriptome data is appropriate for understanding cryptic species diversity in microbial eukaryotes.}, } @article {pmid30445904, year = {2018}, author = {Mohapatra, S and Weisshaar, JC}, title = {Modified Pearson correlation coefficient for two-color imaging in spherocylindrical cells.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {428}, pmid = {30445904}, issn = {1471-2105}, support = {MCB 1512946//Division of Molecular and Cellular Biosciences/ ; }, mesh = {Cells/cytology/*metabolism ; Color ; Correlation of Data ; Humans ; Imaging, Three-Dimensional/*methods ; Microscopy, Fluorescence/*methods ; }, abstract = {The revolution in fluorescence microscopy enables sub-diffraction-limit ("superresolution") localization of hundreds or thousands of copies of two differently labeled proteins in the same live cell. In typical experiments, fluorescence from the entire three-dimensional (3D) cell body is projected along the z-axis of the microscope to form a 2D image at the camera plane. For imaging of two different species, here denoted "red" and "green", a significant biological question is the extent to which the red and green spatial distributions are positively correlated, anti-correlated, or uncorrelated. A commonly used statistic for assessing the degree of linear correlation between two image matrices R and G is the Pearson Correlation Coefficient (PCC). PCC should vary from - 1 (perfect anti-correlation) to 0 (no linear correlation) to + 1 (perfect positive correlation). However, in the special case of spherocylindrical bacterial cells such as E. coli or B. subtilis, we show that the PCC fails both qualitatively and quantitatively. PCC returns the same + 1 value for 2D projections of distributions that are either perfectly correlated in 3D or completely uncorrelated in 3D. The PCC also systematically underestimates the degree of anti-correlation between the projections of two perfectly anti-correlated 3D distributions. The problem is that the projection of a random spatial distribution within the 3D spherocylinder is non-random in 2D, whereas PCC compares every matrix element of R or G with the constant mean value [Formula: see text] or [Formula: see text]. We propose a modified Pearson Correlation Coefficient (MPCC) that corrects this problem for spherocylindrical cell geometry by using the proper reference matrix for comparison with R and G. Correct behavior of MPCC is confirmed for a variety of numerical simulations and on experimental distributions of HU and RNA polymerase in live E. coli cells. The MPCC concept should be generalizable to other cell shapes.}, } @article {pmid30445903, year = {2018}, author = {Iqbal, M and Dubey, M and Gudmundsson, M and Viketoft, M and Jensen, DF and Karlsson, M}, title = {Comparative evolutionary histories of fungal proteases reveal gene gains in the mycoparasitic and nematode-parasitic fungus Clonostachys rosea.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {171}, pmid = {30445903}, issn = {1471-2148}, mesh = {Animals ; Ascomycota/*enzymology/*genetics ; Conserved Sequence ; *Evolution, Molecular ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; *Genes, Fungal ; Nematoda/*microbiology/*parasitology ; Peptide Hydrolases/*genetics/metabolism ; Phylogeny ; }, abstract = {BACKGROUND: The ascomycete fungus Clonostachys rosea (order Hypocreales) can control several important plant diseases caused by plant pathogenic fungi and nematodes. Subtilisin-like serine proteases are considered to play an important role in pathogenesis in entomopathogenic, mycoparasitic, and nematophagous fungi used for biological control. In this study, we analysed the evolutionary histories of protease gene families, and investigated sequence divergence and regulation of serine protease genes in C. rosea.

RESULTS: Proteases of selected hypocrealean fungal species were classified into families based on the MEROPS peptidase database. The highest number of protease genes (590) was found in Fusarium solani, followed by C. rosea with 576 genes. Analysis of gene family evolution identified non-random changes in gene copy numbers in the five serine protease gene families S1A, S8A, S9X, S12 and S33. Four families, S1A, S8A, S9X, and S33, displayed gene gains in C. rosea. A gene-tree / species-tree reconciliation analysis of the S8A family revealed that the gene copy number increase in C. rosea was primarily associated with the S08.054 (proteinase K) subgroup. In addition, regulatory and predicted structural differences, including twelve sites evolving under positive selection, among eighteen C. rosea S8A serine protease paralog genes were also observed. The C. rosea S8A serine protease gene prs6 was induced during interaction with the plant pathogenic species F. graminearum.

CONCLUSIONS: Non-random increases in S8A, S9X and S33 serine protease gene numbers in the mycoparasitic species C. rosea, Trichoderma atroviride and T. virens suggests an involvement in fungal-fungal interactions. Regulatory and predicted structural differences between C. rosea S8A paralogs indicate that functional diversification is driving the observed increase in gene copy numbers. The induction of prs6 expression in C. rosea during confrontation with F. graminearum suggests an involvement of the corresponding protease in fungal-fungal interactions. The results pinpoint the importance of serine proteases for ecological niche adaptation in C. rosea, including a potential role in the mycoparasitic attack on fungal prey.}, } @article {pmid30445640, year = {2018}, author = {Li, C and Sun, X and Conover, JL and Zhang, Z and Wang, J and Wang, X and Deng, X and Wang, H and Liu, B and Wendel, JF and Gong, L}, title = {Cytonuclear coevolution following homoploid hybrid speciation in Aegilops tauschii.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy215}, pmid = {30445640}, issn = {1537-1719}, abstract = {The diploid D-genome lineage of the Triticum/Aegilops complex has an evolutionary history involving genomic contributions from ancient A- and B/S-genome species. We explored here the possible cytonuclear evolutionary responses to this history of hybridization. Phylogenetic analysis of chloroplast DNAs indicate that the D-genome lineage has a maternal origin of the A-genome or some other closely allied lineage. Analyses of the nuclear genome in the D-genome species Aegilops tauschii indicate that accompanying and/or following this ancient hybridization, there has been biased maintenance of maternal A-genome ancestry in nuclear genes encoding cytonuclear enzyme complexes (CECs). Our study provides insights into mechanisms of cytonuclear coevolution accompanying the evolution and eventual stabilization of homoploid hybrid species. We suggest that this coevolutionary process includes likely rapid fixation of A-genome CEC orthologs as well as biased retention of A-genome nucleotides in CEC homologs following population level recombination during the initial generations.}, } @article {pmid30445614, year = {2018}, author = {Teufel, AI and Johnson, MM and Laurent, JM and Kachroo, AH and Marcotte, EM and Wilke, CO}, title = {Withdrawn as Duplicate: The many nuanced evolutionary consequences of duplicated genes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {e1}, doi = {10.1093/molbev/msy216}, pmid = {30445614}, issn = {1537-1719}, } @article {pmid30445604, year = {2018}, author = {Zeibich, L and Schmidt, O and Drake, HL}, title = {Fermenters in the Earthworm Gut: Do Transients Matter?.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy221}, pmid = {30445604}, issn = {1574-6941}, abstract = {Earthworms have profound impact on soil-based ecosystems. Although theoretical considerations suggest that most microbes in the earthworm gut are likely ingested and transient, the non-responsiveness of soil microbes to a specific high value gut nutrient and anoxia has made it difficult to demonstrate that responsive gut fermenters are derived from soil. Therefore, soil and gut content of the model earthworm Lumbricus terrestris were examined for their fermentative capabilities. In unsupplemented anoxic microcosms, fermentation was negligible with soil but rapid with gut content. However, both soil and gut content facilitated robust fermentations when challenged with complex nutrients indicative of those released from gizzard-disrupted cells. Based on the relative abundances of 16S rRNA and 16S rRNA gene sequences, the responsive fermentative taxa in unsupplemented gut content treatments were negligible in unsupplemented soil treatments. In contrast, the responsive fermentative taxa in soil and gut content treatments supplemented with complex nutrients displayed marked similarities, with numerous Proteobacteria- and Firmicutes-affiliated phylotypes being dominant. These findings indicated that detectable differences between the fermentative taxa in soil and gut contents are due in part to the nutrient-dependent metabolic status of community members and reinforce the likelihood that ingested transient microbes contribute to fermentation in the alimentary canal.}, } @article {pmid30445533, year = {2018}, author = {Hu, XJ and Yang, J and Xie, XL and Lv, FH and Cao, YH and Li, WR and Liu, MJ and Wang, YT and Li, JQ and Liu, YG and Ren, YL and Shen, ZQ and Wang, F and Hehua, E and Han, JL and Li, MH}, title = {The genome landscape of Tibetan sheep reveals adaptive introgression from argali and the history of early human settlements on the Qinghai-Tibetan Plateau.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy208}, pmid = {30445533}, issn = {1537-1719}, abstract = {Tibetan sheep are the most common and widespread domesticated animals on the Qinghai-Tibetan Plateau (QTP), and have played an essential role in the permanent human occupation of this high-altitude region. However, the precise timing, route and process of sheep pastoralism in the QTP region remain poorly established, and little is known about the underlying genomic changes that occurred during the process. Here, we investigate the genomic variation in Tibetan sheep using whole-genome sequences, SNP arrays, mitochondrial DNA and Y-chromosomal variants in 986 samples throughout their distribution range. We detect strong signatures of selection in genes involved in the hypoxia and ultraviolet signaling pathways (e.g., HIF-1 pathway and HBB and MITF genes) and in genes associated with morphological traits such as horn size and shape (e.g., RXFP2). We identify clear signals of argali (Ovis ammon) introgression into sympatric Tibetan sheep, covering 5.23% - 5.79% of their genomes. The introgressed genomic regions are enriched in genes related to oxygen transportation system, sensory perception and morphological phenotypes, in particular the genes HBB and RXFP2 with strong signs of adaptive introgression. The spatial distribution of genomic diversity and demographic reconstruction of the history of Tibetan sheep shows a stepwise pattern of colonization with their initial spread onto the QTP from its northeastern part c. 3,100 years ago, followed by further southwest expansion to the central QTP c. 1,300 years ago. Together with archeological evidence, the date and route reveals the history of human expansions on the QTP by the Tang-Bo Ancient Road during the late-Holocene. Our findings contribute to a depth understanding of early pastoralism and the local adaptation of Tibetan sheep as well as the late-Holocene human occupation of the QTP.}, } @article {pmid30445510, year = {2018}, author = {Saxena, AS and Salomon, MP and Matsuba, C and Yeh, SD and Baer, CF}, title = {Evolution of the mutational process under relaxed selection in Caenorhabditis elegans.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy213}, pmid = {30445510}, issn = {1537-1719}, abstract = {The mutational process varies at many levels, from within genomes to among taxa. Many mechanisms have been linked to variation in mutation, but understanding of the evolution of the mutational process is rudimentary. Physiological condition is often implicated as a source of variation in microbial mutation rate and may contribute to mutation rate variation in multicellular organisms.Deleterious mutations are a ubiquitous source of variation in condition. We test the hypothesis that the mutational process depends on the underlying mutation load in two groups of Caenorhabditis elegans mutation accumulation (MA) lines that differ in their starting mutation loads. "First-Order MA" (O1MA) lines maintained under minimal selection for ∼250 generations were divided into high-fitness and low-fitness groups and sets of "second-order MA" (O2MA) lines derived from each O1MA line were maintained for ∼150 additional generations. Genomes of 48 O2MA lines and their progenitors were sequenced. There is significant variation among O2MA lines in base-substitution rate (µbs), but no effect of initial fitness; the indel rate is greater in high-fitness O2MA lines. Overall, µbs is positively correlated with recombination and proximity to short tandem repeats and negatively correlated with 10 bp and 1 Kb GC content. However, probability of mutation is sufficiently predicted by the three-nucleotide motif alone. ∼90% of the variance in standing nucleotide variation is explained by mutability. Total mutation rate increased in the O2MA lines, as predicted by the "drift barrier" model of mutation rate evolution. These data, combined with experimental estimates of fitness, suggest that epistasis is synergistic.}, } @article {pmid30445505, year = {2018}, author = {Parker, DJ and Bast, J and Jalvingh, K and Dumas, Z and Robinson-Rechavi, M and Schwander, T}, title = {Repeated evolution of asexuality involves convergent gene expression changes.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy217}, pmid = {30445505}, issn = {1537-1719}, abstract = {Asexual reproduction has evolved repeatedly from sexual ancestors across a wide range of taxa. While the costs and benefits associated with asexuality have received considerable attention, the molecular changes underpinning the evolution of asexual reproduction remain relatively unexplored. In particular, it is completely unknown whether the repeated evolution of asexual phenotypes involves similar molecular changes, as previous studies have focused on changes occurring in single lineages. Here we investigate the extent of convergent gene expression changes across five independent transitions to asexuality in stick insects. We compared gene expression of asexual females to females of close sexual relatives in whole-bodies, reproductive tracts, and legs. We identified a striking amount of convergent gene expression change (up to 8% of genes), greatly exceeding that expected by chance. Convergent changes were also tissue-specific, and most likely driven by selection for functional changes. Genes showing convergent changes in the reproductive tract were associated with meiotic spindle formation and centrosome organization. These genes are particularly interesting as they can influence the production of unreduced eggs, a key barrier to asexual reproduction. Changes in legs and whole-bodies were likely involved in female sexual trait decay, with enrichment in terms such as sperm-storage and pigmentation. By identifying changes occurring across multiple independent transitions to asexuality, our results provide a rare insight into the molecular basis of asexual phenotypes and suggest that the evolutionary path to asexuality is highly constrained, requiring repeated changes to the same key genes.}, } @article {pmid30445501, year = {2018}, author = {Holt, S and Miks, MH and de Carvalho, BT and Foulquié-Moreno, MR and Thevelein, JM}, title = {The molecular biology of fruity and floral aromas in beer and other alcoholic beverages.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuy041}, pmid = {30445501}, issn = {1574-6976}, abstract = {Aroma compounds provide attractiveness and variety to alcoholic beverages. We discuss the molecular biology of a major subset of beer aroma volatiles, fruity and floral compounds, originating from raw materials (malt and hops), or formed by yeast during fermentation. We introduce aroma perception, describe the most aroma-active, fruity and floral compounds in fruits and their presence and origin in beer. They are classified into categories based on their functional groups and biosynthesis pathways: 1) Higher alcohols and esters, 2) Polyfunctional thiols, 3) Lactones and furanones, and 4) Terpenoids. Yeast and hops are the main sources of fruity and flowery aroma compounds in beer. For yeast, the focus is on higher alcohols and esters, and particularly the complex regulation of the alcohol acetyl transferase ATF1 gene. We discuss the release of polyfunctional thiols and monoterpenoids from cysteine- and glutathione-S-conjugated compounds and glucosides, respectively, the primary biological functions of the yeast enzymes involved, their mode of action and mechanisms of regulation that control aroma compound production. Furthermore, we discuss biochemistry and genetics of terpenoid production and formation of non-volatile precursors in Humulus lupulus (hops). Insight in these pathways provides a toolbox for creating innovative products with a diversity of pleasant aromas.}, } @article {pmid30445055, year = {2019}, author = {Planques, A and Malem, J and Parapar, J and Vervoort, M and Gazave, E}, title = {Morphological, cellular and molecular characterization of posterior regeneration in the marine annelid Platynereis dumerilii.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {189-210}, doi = {10.1016/j.ydbio.2018.11.004}, pmid = {30445055}, issn = {1095-564X}, abstract = {Regeneration, the ability to restore body parts after an injury or an amputation, is a widespread but highly variable and complex phenomenon in animals. While having fascinated scientists for centuries, fundamental questions about the cellular basis of animal regeneration as well as its evolutionary history remain largely unanswered. Here, we present a study of regeneration of the marine annelid Platynereis dumerilii, an emerging comparative developmental biology model, which, like many other annelids, displays important regenerative abilities. When P. dumerilii worms are amputated, they are able to regenerate the posteriormost differentiated part of their body and a stem cell-rich growth zone that allows the production of new segments replacing the amputated ones. We show that posterior regeneration is a rapid process that follows a well reproducible path and timeline, going through specific stages that we thoroughly defined. Wound healing is achieved one day after amputation and a regeneration blastema forms one day later. At this time point, some tissue specification already occurs, and a functional posterior growth zone is re-established as early as three days after amputation. Regeneration timing is only influenced, in a minor manner, by worm size. Comparable regenerative abilities are found for amputations performed at different positions along the antero-posterior axis of the worm, except when amputation planes are very close to the pharynx. Regenerative abilities persist upon repeated amputations without important alterations of the process. We also show that intense cell proliferation occurs during regeneration and that cell divisions are required for regeneration to proceed normally. Finally, 5-ethynyl-2'-deoxyuridine (EdU) pulse and chase experiments suggest that blastemal cells mostly derive from the segment immediately abutting the amputation plane. The detailed characterization of P. dumerilii posterior body regeneration presented in this article provides the foundation for future mechanistic and comparative studies of regeneration in this species.}, } @article {pmid30444662, year = {2018}, author = {Mullon, C and Lehmann, L}, title = {Eco-Evolutionary Dynamics in Metacommunities: Ecological Inheritance, Helping within Species, and Harming between Species.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {664-686}, doi = {10.1086/700094}, pmid = {30444662}, issn = {1537-5323}, abstract = {Understanding selection on intra- and interspecific interactions that take place in dispersal-limited communities is a challenge for ecology and evolutionary biology. The problem is that local demographic stochasticity generates eco-evolutionary dynamics that are generally too complicated to make tractable analytical investigations. Here we circumvent this problem by approximating the selection gradient on a quantitative trait that influences local community dynamics, assuming that such dynamics are deterministic with a stable fixed point. The model nonetheless captures unavoidable kin selection effects arising from demographic stochasticity. Our approximation reveals that selection depends on how an individual expressing a trait change influences (1) its own fitness and the fitness of its current relatives and (2) the fitness of its downstream relatives through modifications of local ecological conditions (i.e., through ecological inheritance). Mathematically, the effects of ecological inheritance on selection are captured by dispersal-limited versions of press perturbations of community ecology. We use our approximation to investigate the evolution of helping within species and harming between species when these behaviors influence demography. We find that altruistic helping evolves more readily when intraspecific competition is for material resources rather than for space, because in this case the costs of kin competition tend to be paid by downstream relatives. Similarly, altruistic harming between species evolves when it alleviates downstream relatives from interspecific competition. Beyond these examples, our approximation can help better understand the influence of ecological inheritance on a variety of eco-evolutionary dynamics in metacommunities, from consumer-resource and predator-prey coevolution to selection on mating systems with demographic feedbacks.}, } @article {pmid30444661, year = {2018}, author = {Holding, T and Valletta, JJ and Recker, M}, title = {Multiscale Immune Selection and the Transmission-Diversity Feedback in Antigenically Diverse Pathogen Systems.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {E189-E201}, doi = {10.1086/699535}, pmid = {30444661}, issn = {1537-5323}, abstract = {Antigenic diversity is commonly used by pathogens to enhance their transmission success. Within-host clonal antigenic variation helps to maintain long infectious periods, whereas high levels of allelic diversity at the population level significantly expand the pool of susceptible individuals. Diversity, however, is not necessarily a static property of a pathogen population but in many cases is generated by the very act of infection and transmission, and it is therefore expected to respond dynamically to changes in transmission and immune selection. We hypothesized that this coupling creates a positive feedback whereby infection and disease transmission promote the generation of diversity, which itself facilitates immune evasion and further infections. To investigate this link in more detail, we considered the human malaria parasite Plasmodium falciparum, one of the most important antigenically diverse pathogens. We developed an individual-based model in which antigenic diversity emerges as a dynamic property from the underlying transmission processes. Our results show that the balance between stochastic extinction and the generation of new antigenic variants is intrinsically linked to within-host and between-host immune selection. This in turn determines the level of diversity that can be maintained in a given population. Furthermore, the transmission-diversity feedback can lead to temporal lags in the response to natural or intervention-induced perturbations in transmission rates. Our results therefore have important implications for monitoring and assessing the effectiveness of disease control efforts.}, } @article {pmid30444660, year = {2018}, author = {Rohner, PT and Blanckenhorn, WU}, title = {A Comparative Study of the Role of Sex-Specific Condition Dependence in the Evolution of Sexually Dimorphic Traits.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {E202-E215}, doi = {10.1086/700096}, pmid = {30444660}, issn = {1537-5323}, abstract = {Sexual selection can displace traits acting as ornaments or armaments from their viability optimum in one sex, ultimately giving rise to sexual dimorphism. The degree of dimorphism should not only mirror the strength of sexual selection but also the net viability costs of trait maintenance at equilibrium. As the ability of organisms to bear exaggerated traits will depend on their condition, more sexually dimorphic traits should also exhibit greater sex differences in condition dependence. While this has been demonstrated among traits within species, similar patterns are expected across the phylogeny. We investigated this prediction within and across 11 (sub)species of sepsid flies with varying mating systems. When estimating condition dependence for seven sexual and nonsexual traits that vary in their sexual dimorphism, we not only found a positive relationship between the sex difference in allometric slopes (our measure of condition dependence) and relative trait exaggeration within species but also across species for those traits expected to be under sexual selection. Species with more pronounced male aggression further had relatively larger and more condition-dependent male fore- and midlegs. Our comparative study suggests a common genetic/developmental basis of sexual dimorphism and sex-specific plasticity that evolves across the phylogeny-and that the evolution of size consistently alters scaling relationships and thus contributes to the allometric variation of sexual armaments or ornaments in animals.}, } @article {pmid30444659, year = {2018}, author = {Rebolleda-Gómez, M and Travisano, M}, title = {The Cost of Being Big: Local Competition, Importance of Dispersal, and Experimental Evolution of Reversal to Unicellularity.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {731-744}, doi = {10.1086/700095}, pmid = {30444659}, issn = {1537-5323}, abstract = {Multicellularity provides multiple benefits. Nonetheless, unicellularity is ubiquitous, and there have been multiple cases of evolutionary reversal to a unicellular organization. In this article, we explore some of the costs of multicellularity as well as the possibility and dynamics of evolutionary reversals to unicellularity. We hypothesize that recently evolved multicellular organisms would face a high cost of increased competition for local resources in spatially structured environments because of larger size and increased cell densities. To test this hypothesis we conducted competition assays, computer simulations, and selection experiments using isolates of Saccharomyces cerevisiae that recently evolved multicellularity. In well-mixed environments, multicellular isolates had lower growth rates relative to their unicellular ancestor because of limitations of space and resource acquisition. In structured environments with localized resources, cells in both multicellular and unicellular isolates grew at a similar rate. Despite similar growth, higher local density of cells in multicellular groups led to increased competition and higher fitness costs in spatially structured environments. In structured environments all of the multicellular isolates rapidly evolved a predominantly unicellular life cycle, while in well-mixed environments reversal was more gradual. Taken together, these results suggest that a lack of dispersal, leading to higher local competition, might have been one of the main constraints in the evolution of early multicellular forms.}, } @article {pmid30444658, year = {2018}, author = {Wadgymar, SM and Mactavish, RM and Anderson, JT}, title = {Transgenerational and Within-Generation Plasticity in Response to Climate Change: Insights from a Manipulative Field Experiment across an Elevational Gradient.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {698-714}, doi = {10.1086/700097}, pmid = {30444658}, issn = {1537-5323}, abstract = {Parental environmental effects-or transgenerational plasticity-can influence an individual's phenotype or fitness yet remain underexplored in the context of global change. Using the perennial self-pollinating plant Boechera stricta, we explored the effects of climate change on transgenerational and within-generation plasticity in dormancy, germination, growth, and survival. We first conducted a snow removal experiment in the field, in which we transplanted 16 families of known origin into three common gardens at different elevations and exposed half of the siblings to contemporary snow dynamics and half to early snow removal. We planted the offspring of these individuals in a factorial manipulation of temperature and water level in the growth chamber and reciprocally transplanted them across all parental environments in the field. The growth chamber experiment revealed that the effects of transgenerational plasticity persist in traits expressed after establishment, even when accounting for parental effects on seed mass. The field experiment showed that transgenerational and within-generation plasticity can interact and that plasticity varies clinally in populations distributed across elevations. These findings demonstrate that transgenerational plasticity can influence fitness-related traits and should be incorporated in studies of biological responses to climate change.}, } @article {pmid30444657, year = {2018}, author = {Sparks, AM and Watt, K and Sinclair, R and Pilkington, JG and Pemberton, JM and Johnston, SE and McNeilly, TN and Nussey, DH}, title = {Natural Selection on Antihelminth Antibodies in a Wild Mammal Population.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {745-760}, doi = {10.1086/700115}, pmid = {30444657}, issn = {1537-5323}, abstract = {An effective immune response is expected to confer fitness benefits through improved resistance to parasites but also incur energetic costs that negatively impact fitness-related traits, such as reproduction. The fitness costs and benefits of an immune response are likely to depend on host age, sex, and levels of parasite exposure. Few studies have examined the full extent to which patterns of natural selection on immune phenotypes vary across demographic groups and environments in the wild. Here, we assessed natural selection on plasma levels of three functionally distinct isotypes (IgA, IgE, and IgG) of antibodies against a prevalent nematode parasite measured in a wild Soay sheep population over 26 years. We found little support for environment-dependent selection or reproductive costs. However, antibody levels were negatively associated with parasite egg counts and positively associated with subsequent survival, albeit in a highly age- and isotype-dependent manner. Raised levels of antiparasite IgA best predicted reduced egg counts, but this did not predict survival in lambs. In adults increased antiparasite IgG predicted reduced egg counts, and in adult females IgG levels also positively predicted overwinter survival. Our results highlight the potential importance of age- and sex-dependent selection on immune phenotypes in nature and show that patterns of selection can vary even among functionally related immune markers.}, } @article {pmid30444656, year = {2018}, author = {Bernhardt, JR and Sunday, JM and O'Connor, MI}, title = {Metabolic Theory and the Temperature-Size Rule Explain the Temperature Dependence of Population Carrying Capacity.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {687-697}, doi = {10.1086/700114}, pmid = {30444656}, issn = {1537-5323}, abstract = {The temperature dependence of highly conserved subcellular metabolic systems affects ecological patterns and processes across scales, from organisms to ecosystems. Population density at carrying capacity plays an important role in evolutionary processes, biodiversity, and ecosystem function, yet how it varies with temperature-dependent metabolism remains unclear. Though the exponential effect of temperature on intrinsic population growth rate, r, is well known, we still lack clear evidence that population density at carrying capacity, K, declines with increasing per capita metabolic rate, as predicted by the metabolic theory of ecology (MTE). We experimentally tested whether temperature effects on photosynthesis propagate directly to population carrying capacity in a model species, the mobile phytoplankton Tetraselmis tetrahele. After maintaining populations at a fixed resource supply and fixed temperatures for 43 days, we found that carrying capacity declined with increasing temperature. This decline was predicted quantitatively when models included temperature-dependent metabolic rates and temperature-associated body-size shifts. Our results demonstrate that warming reduces carrying capacity and that temperature effects on body size and metabolic rate interact to determine how temperature affects population dynamics. These findings bolster efforts to relate metabolic temperature dependence to population and ecosystem patterns via MTE.}, } @article {pmid30444655, year = {2018}, author = {Simms, E and Caruso, C}, title = {Treasurer's Report, 2017: Statement of Activities For the year ending December 31, 2017.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {786-787}, doi = {10.1086/700554}, pmid = {30444655}, issn = {1537-5323}, } @article {pmid30444654, year = {2018}, author = {Brengdahl, M and Kimber, CM and Maguire-Baxter, J and Malacrinò, A and Friberg, U}, title = {Genetic Quality Affects the Rate of Male and Female Reproductive Aging Differently in Drosophila melanogaster.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {761-772}, doi = {10.1086/700117}, pmid = {30444654}, issn = {1537-5323}, abstract = {Males and females often maximize fitness by pursuing different reproductive strategies, with males commonly assumed to benefit more from increased resource allocation into current reproduction. Such investment should trade off with somatic maintenance and may explain why males frequently live shorter than females. It also predicts that males should experience faster reproductive aging. Here we investigate whether reproductive aging and life span respond to condition differently in male and female Drosophila melanogaster, as predicted if sexual selection has shaped male and female resource-allocation patterns. We manipulate condition through genetic quality by comparing individuals inbred or outbred for a major autosome. While genetic quality had a similar effect on condition in both sexes, condition had a much larger general effect on male reproductive output than on female reproductive output, as expected when sexual selection on vigor acts more strongly on males. We find no differences in reproductive aging between the sexes in low condition, but in high condition reproductive aging is relatively faster in males. No corresponding sex-specific change was found for life span. The sex difference in reproductive aging appearing in high condition was specifically due to a decreased aging rate in females rather than any change in males. Our results suggest that females age slower than males in high condition primarily because sexual selection has favored sex differences in resource allocation under high condition, with females allocating relatively more toward somatic maintenance than males.}, } @article {pmid30444653, year = {2018}, author = {Tinghitella, RM and Broder, ED and Gurule-Small, GA and Hallagan, CJ and Wilson, JD}, title = {Purring Crickets: The Evolution of a Novel Sexual Signal.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {773-782}, doi = {10.1086/700116}, pmid = {30444653}, issn = {1537-5323}, abstract = {Opportunities to observe contemporary signal change are incredibly rare but critical for understanding how diversity is created and maintained. We discovered a population of the Pacific field cricket (Teleogryllus oceanicus) with a newly evolved song (purring), different from any known cricket. Male crickets use song to attract females from afar and to court females once near. Teleogryllus oceanicus is well known for sexual signal evolution, as exemplified by a recent signal loss. In this study, we characterized the new purring sound and investigated the role of the purr in long-distance and short-distance communication. The purring sound differed from typical ancestral calls in peak frequency, amplitude, and bandwidth. Further, the long-distance purring song facilitated mate location, though the role of courtship purring song is less clear. Our discovery of purring male crickets is an unprecedented opportunity to watch the emergence of a newly evolved sexual signal unfold in real time and has potential to illuminate the mechanisms by which evolutionary novelties arise and coevolve between the sexes.}, } @article {pmid30444652, year = {2018}, author = {Bronstein, JL and Bolnick, DI}, title = {"Her Joyous Enthusiasm for Her Life-Work …": Early Women Authors in The American Naturalist.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {655-663}, doi = {10.1086/700119}, pmid = {30444652}, issn = {1537-5323}, abstract = {Women have long been underrepresented in the natural sciences, and although great progress has been made in recent decades, many subtle and not-so-subtle barriers persist. In this context, it is easy to get the impression that the early history of ecology and evolutionary biology was exclusively the domain of male researchers. In fact, a number of women made very substantial contributions to The American Naturalist in its first decades. In a follow-up to a series of retrospective essays celebrating 150 years of this journal, we highlight the scientific contributions of the women published in it during its first 50 years (1867-1916). We also discuss the diverse paths that their scientific careers took and the barriers they faced along the way.}, } @article {pmid30444651, year = {2018}, author = {Lau, J}, title = {Secretary's Report, 2018: American Society of Naturalists.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {783-785}, doi = {10.1086/700647}, pmid = {30444651}, issn = {1537-5323}, } @article {pmid30444650, year = {2018}, author = {O'Brien, AM and Sawers, RJH and Ross-Ibarra, J and Strauss, SY}, title = {Evolutionary Responses to Conditionality in Species Interactions across Environmental Gradients.}, journal = {The American naturalist}, volume = {192}, number = {6}, pages = {715-730}, doi = {10.1086/700118}, pmid = {30444650}, issn = {1537-5323}, abstract = {The outcomes of many species interactions are conditional on the environments in which they occur. Often, interactions grade from being more positive under stressful or low-resource conditions to more antagonistic or neutral under benign conditions. Here, we take predictions about two well-supported ecological theories on conditionality-limiting resource models and the stress-gradient hypothesis-and combine them with those from the geographic mosaic theory of coevolution (GMTC) to generate predictions for systematic patterns of adaptation and coadaptation between partners along abiotic gradients. When interactions become more positive in stressful environments, mutations that increase fitness in one partner may also increase fitness in the other; because fitnesses are aligned, selection should favor greater mutualistic adaptation and coadaptation between interacting species in stressful ends of environmental gradients. As a corollary, in benign environments antagonistic coadaptation could result in Red Queen or arms-race dynamics or the reduction of antagonism through character displacement and niche partitioning. Here, we distinguish between generally mutualistic or antagonistic adaptation (i.e., mutations in one partner that have similar effects across multiple populations of the other) and specific adaptations to sympatric partners (local adaptation), which can occur either alone or simultaneously. We then outline the kinds of data required to test these predictions, develop experimental designs and statistical methods, and demonstrate these using simulations based on GMTC models. Our methods can be applied to a range of conditional outcomes and may also be useful in assisted translocation approaches in the face of climate change.}, } @article {pmid30444563, year = {2018}, author = {Zeder, MA}, title = {Why evolutionary biology needs anthropology: Evaluating core assumptions of the extended evolutionary synthesis.}, journal = {Evolutionary anthropology}, volume = {27}, number = {6}, pages = {267-284}, doi = {10.1002/evan.21747}, pmid = {30444563}, issn = {1520-6505}, mesh = {Animals ; *Anthropology, Physical ; *Biological Evolution ; Heredity ; Humans ; Models, Biological ; }, abstract = {Anthropologists have a long history of applying concepts from evolutionary biology to cultural evolution. Evolutionary biologists, however, have been slow to turn to anthropology for insights about evolution. Recently, evolutionary biology has been engaged in a debate over the need to revise evolutionary theory to account for developments made in 60 years since the Modern Synthesis, the standard evolutionary paradigm, was framed. Revision proponents maintain these developments challenge central tenets of standard theory that can only be accounted for in an extended evolutionary synthesis (EES). Anthropology has much to offer to this debate. One important transition in human cultural evolution, the domestication of plants and animals, provides an ideal model system assessing core EES assumptions about directionality, causality, targets of selection, modes of inheritance, and pace of evolution. In so doing, anthropologists contribute to an overarching framework that brings together cultural and biological evolution.}, } @article {pmid30444473, year = {2019}, author = {Sun, Y and Jiang, ZM and Zhao, LL and Su, J and Yu, LY and Tian, YQ and Zhang, YQ}, title = {Allorhizocola rhizosphaerae gen. nov., sp. nov., a new member of Micromonosporaceae isolated from rhizosphere soil of the plant Calligonum mongolicum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {109-115}, doi = {10.1099/ijsem.0.003114}, pmid = {30444473}, issn = {1466-5034}, abstract = {The taxonomic position of an actinobacterium, designated CPCC 204380T, which was isolated from a rhizosphere soil sample of the plant Calligonum mongolicum collected from Xinjiang Province, China, was established using a polyphasic approach. Vegetative hyphae developed well and globose bodies formed from aged hyphae. Spore chains that differentiated from the vegetative hyphae contained non-motile rod-shaped spores. The peptidoglycan contained meso-diaminopimelic acid and 3-hydroxydiaminopimelic acid as the diagnostic amino acids. The acyl type of the peptidoglycan was glycolyl. Glucose, mannose, ribose and xylose were detected in whole-cell hydrolysates. The predominant menaquinone was MK-10(H8), followed by MK-10(H6) and MK-10(H4). The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. The major fatty acids were iso-C15 : 0, iso-C16 : 0 and C17 : 1ω9c. The genomic G+C content was 64.9 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CPCC 204380T should be placed in the family Micromonosporaceae, in which it formed a distinct lineage next to the genera Rhizocola, Catellatospora, Catelliglobosispora, Hamadaea and Allocatelliglobosispora. It shared the highest 16S rRNA gene sequence similarities with Rhizocola hellebori K12-0602T (96.1 %), Catellatospora chokoriensis 2-25/1T (95.9 %), Catelliglobosispora koreensis DSM 44566T (95.9 %), Hamadaea tsunoensis DSM 44101T (95.3 %) and Allocatelliglobosispora scoriae Sco-B14 T (94.2 %), and less than 94.0 % sequence similarity with other validly described species. The combination of phylogenetic analysis and phenotypic characteristics supported the proposal of strain CPCC 204380T as representing a novel species of a new genus in the family Micromonosporaceae, for which the name Allorhizocola rhizosphaerae gen. nov., sp. nov. is proposed. CPCC 204380T (=DSM 102292T=KCTC 39746 T) is the type strain of the type species.}, } @article {pmid30444472, year = {2019}, author = {Trujillo, ME and Oren, A and Garrity, GM}, title = {Preparation of the Validation Lists and the role of the List Editors.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {3-4}, doi = {10.1099/ijsem.0.003106}, pmid = {30444472}, issn = {1466-5034}, abstract = {Recently a number of queries were received about the ways in which requests for validation of names of taxa effectively published in journals other than the IJSEM are approved or denied and about the criteria used by the List Editors of the journal when deciding whether or not a validation request can be approved. As this process may be unclear to some authors of proposals, we would like to clarify the nature of the validation process and the role of the List Editors.}, } @article {pmid30444470, year = {2019}, author = {Duangupama, T and Pittayakhajonwut, P and Thawai, C}, title = {Thermocatellispora soli sp. nov., isolated from hot spring soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {134-138}, doi = {10.1099/ijsem.0.003115}, pmid = {30444470}, issn = {1466-5034}, abstract = {An aerobic, spore-forming, actinomycete, designated strain CHM3-46T, was isolated from soil in a hot spring pond located in Chiangmai province, Thailand. The strain exhibited taxonomic characteristics consistent with the genus Thermocatellispora. Strain CHM3-46T produced short, straight chains of warty spores on aerial mycelia. The presence of meso-diaminopimelic acid was observed in the cell-wall peptidoglycan. The whole-cell reducing sugars were glucose, mannose, galacose and ribose. The phospholipids comprised phosphatidylmethylethanolamine, hydroxyphosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol, four phosphoglycolipids and three unidentified phospholipids. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H8). 10-methyl C17 : 0, C16 : 0, C17 : 0 and iso-C16 : 0 were identified as the main cellular fatty acids. The G+C content of the genomic DNA was 73.2 mol%. Analysis of the 16S rRNA gene sequence showed that strain CHM3-46T belonged to the genus Thermocatellispora, exhibiting the highest similarity to Thermocatellispora tengchongensis YIM 77521T (98.5 %). Furthermore, a low DNA relatedness value (23.4 %±0.8) and several physiological and biochemical characteristic differences were detected between strain CHM3-46T and its closest relative. Based on the taxonomic data, strain CHM3-46T could be readily distinguished from its closest phylogenetic relative and represents a novel species, for which the name Thermocatellisporasoli sp. nov. is proposed. The type strain is CHM3-46T (=TBRC 7649T=NBRC 113148T).}, } @article {pmid30443803, year = {2018}, author = {Lemskaya, NA and Kulemzina, AI and Beklemisheva, VR and Biltueva, LS and Proskuryakova, AA and Hallenbeck, JM and Perelman, PL and Graphodatsky, AS}, title = {A combined banding method that allows the reliable identification of chromosomes as well as differentiation of AT- and GC-rich heterochromatin.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {4}, pages = {307-315}, doi = {10.1007/s10577-018-9589-9}, pmid = {30443803}, issn = {1573-6849}, support = {18-04-00826//Russian Foundation for Basic Research/ ; 16-14-10009//Russian Science Foundation/ ; }, abstract = {Сonstitutive heterochromatin areas are revealed by differential staining as C-positive chromosomal regions. These C-positive bands may greatly vary by location, size, and nucleotide composition. CBG-banding is the most commonly used method to detect structural heterochromatin in animals. The difficulty in identification of individual chromosomes represents an unresolved problem of this method as the body of the chromosome is stained uniformly and does not have banding pattern beyond C-bands. Here, we present the method that we called CDAG for sequential heterochromatin staining after differential GTG-banding. The method uses G-banding followed by heat denaturation in the presence of formamide with consecutive fluorochrome staining. The new technique is valid for the concurrent revealing of heterochromatin position due to differential banding of chromosomes and heterochromatin composition (AT-/GC-rich) in animal karyotyping.}, } @article {pmid30443686, year = {2018}, author = {Song, W and Wang, S and Shen, J and Zhu, B}, title = {Complete Genome Sequence of Massilia oculi sp. nov. CCUG 43427T (=DSM 26321T), the Type Strain of M. oculi, and Comparison with Genome Sequences of Other Massilia Strains.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1597-7}, pmid = {30443686}, issn = {1432-0991}, support = {2017YFD0201108//National Key R&D Program of China/ ; 2018YFD0201202//National Key R&D Program of China/ ; LY17C010006//Natural Zhejiang National Natural Science Foundation of China/ ; SKLOF201802//State Key Laboratory for Biology of Plant Diseases and Insect Pests/ ; }, abstract = {Massilia oculi sp. nov. of type strain CCUG 43427T is a Gram-negative, rod-shaped, nonspore-forming bacterium, which was recently isolated from the eye of a patient suffering from endophthalmitis and was described as novel species in Massilia genus. In this study, we present the complete genome sequence of this strain by using Pacbio SMRT cell platform and compare this sequence with the genomes of 30 Massilia representative strains. Also, a comprehensive search was conducted for genes and proteins involved in antibiotic resistance and pathogenicity. The genome of CCUG 43427T is 5,844,653 bp with 65.55% GC content. This genome contains four prophages and four genomic islands (GIs). The cobalt/zinc/cadmium transporter locus CzcABCD is included in these GIs. This GI was predicted to play important role in bacterial heavy-metal tolerance. The in silico genome analysis also revealed that this strain contains a lot of antibiotic resistance and pathogenicity related genes. This result suggested that this strain may has evolved a wide arsenal of weapons for pathogenicity and survival. Genome comparison among CCUG 43427T and other 30 Massilia strains revealed that more than 400 genes are unique in CCUG 43427T. Among these, one gene cluster, which was annotated to be important for LOS biosynthesis, catalytic mechanism and the substrate specificity of the enzyme, was predicted to be horizontally transferred by using phylogenies and biased GC content.}, } @article {pmid30443148, year = {2018}, author = {Kalthoff, DC and Green, JL}, title = {Feeding Ecology in Oligocene Mylodontoid Sloths (Mammalia, Xenarthra) as Revealed by Orthodentine Microwear Analysis.}, journal = {Journal of mammalian evolution}, volume = {25}, number = {4}, pages = {551-564}, pmid = {30443148}, issn = {1064-7554}, abstract = {Recently, dental microwear analysis has been successfully employed to xenarthran teeth. Here, we present new data on use wear features on 16 molariforms of Orophodon hapaloides and Octodontotherium grande. These taxa count among the earliest sloths and are known from the Deseadan SALMA (late Oligocene). Modern phylogenetic analyses classify Octodontotherium and Orophodon within Mylodontoidea with whom they share lobate cheek teeth with an outer layer of cementum and a thick layer of orthodentine. Similar target areas of 100μm2 were analyzed on the orthodentine surface of each tooth by stereomicroscopic microwear and by SEM microwear. Results were unlike those of extant sloths (stereomicroscopic microwear: Bradypus, Choloepus) and published data from fossil sloths (SEM microwear: Acratocnus, Megalonyx, Megatherium, Thinobadistes); thus, both approaches independently indicate a different feeding ecology for the Oligocene taxa. The unique microwear results suggest that both taxa fed on plant material with low to moderate intrinsic toughness (foliage, twigs) but also proposes intake of tougher food items (e.g., seeds). Frequent gouging of the tooth surfaces can be explained by exogenous influence on microwear, such as possible intake of abrasive grit. We suggest an unspecialized herbivorous diet for Octodontotherium and Orophodon utilizing diverse food resources of their habitat. These interpretations support the reconstruction of (1) Deseadan environments as open habitats with spreading savannas/grasslands and (2) both taxa as wide-muzzled bulk feeders at ground level.}, } @article {pmid30442811, year = {2018}, author = {Marchio, E}, title = {Climbing out of the bottle.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {862}, doi = {10.1126/science.362.6416.862}, pmid = {30442811}, issn = {1095-9203}, } @article {pmid30442810, year = {2018}, author = {Visnes, T and Cázares-Körner, A and Hao, W and Wallner, O and Masuyer, G and Loseva, O and Mortusewicz, O and Wiita, E and Sarno, A and Manoilov, A and Astorga-Wells, J and Jemth, AS and Pan, L and Sanjiv, K and Karsten, S and Gokturk, C and Grube, M and Homan, EJ and Hanna, BMF and Paulin, CBJ and Pham, T and Rasti, A and Berglund, UW and von Nicolai, C and Benitez-Buelga, C and Koolmeister, T and Ivanic, D and Iliev, P and Scobie, M and Krokan, HE and Baranczewski, P and Artursson, P and Altun, M and Jensen, AJ and Kalderén, C and Ba, X and Zubarev, RA and Stenmark, P and Boldogh, I and Helleday, T}, title = {Small-molecule inhibitor of OGG1 suppresses proinflammatory gene expression and inflammation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {834-839}, doi = {10.1126/science.aar8048}, pmid = {30442810}, issn = {1095-9203}, support = {P01 AI062885/AI/NIAID NIH HHS/United States ; }, abstract = {The onset of inflammation is associated with reactive oxygen species and oxidative damage to macromolecules like 7,8-dihydro-8-oxoguanine (8-oxoG) in DNA. Because 8-oxoguanine DNA glycosylase 1 (OGG1) binds 8-oxoG and because Ogg1-deficient mice are resistant to acute and systemic inflammation, we hypothesized that OGG1 inhibition may represent a strategy for the prevention and treatment of inflammation. We developed TH5487, a selective active-site inhibitor of OGG1, which hampers OGG1 binding to and repair of 8-oxoG and which is well tolerated by mice. TH5487 prevents tumor necrosis factor-α-induced OGG1-DNA interactions at guanine-rich promoters of proinflammatory genes. This, in turn, decreases DNA occupancy of nuclear factor κB and proinflammatory gene expression, resulting in decreased immune cell recruitment to mouse lungs. Thus, we present a proof of concept that targeting oxidative DNA repair can alleviate inflammatory conditions in vivo.}, } @article {pmid30442809, year = {2018}, author = {Chorev, DS and Baker, LA and Wu, D and Beilsten-Edmands, V and Rouse, SL and Zeev-Ben-Mordehai, T and Jiko, C and Samsudin, F and Gerle, C and Khalid, S and Stewart, AG and Matthews, SJ and Grünewald, K and Robinson, CV}, title = {Protein assemblies ejected directly from native membranes yield complexes for mass spectrometry.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {829-834}, doi = {10.1126/science.aau0976}, pmid = {30442809}, issn = {1095-9203}, support = {//European Research Council/International ; //Wellcome Trust/United Kingdom ; //CIHR/Canada ; }, abstract = {Membrane proteins reside in lipid bilayers and are typically extracted from this environment for study, which often compromises their integrity. In this work, we ejected intact assemblies from membranes, without chemical disruption, and used mass spectrometry to define their composition. From Escherichia coli outer membranes, we identified a chaperone-porin association and lipid interactions in the β-barrel assembly machinery. We observed efflux pumps bridging inner and outer membranes, and from inner membranes we identified a pentameric pore of TonB, as well as the protein-conducting channel SecYEG in association with F1FO adenosine triphosphate (ATP) synthase. Intact mitochondrial membranes from Bos taurus yielded respiratory complexes and fatty acid-bound dimers of the ADP (adenosine diphosphate)/ATP translocase (ANT-1). These results highlight the importance of native membrane environments for retaining small-molecule binding, subunit interactions, and associated chaperones of the membrane proteome.}, } @article {pmid30442808, year = {2018}, author = {Nicholson, CW and Lücke, A and Schmidt, WG and Puppin, M and Rettig, L and Ernstorfer, R and Wolf, M}, title = {Beyond the molecular movie: Dynamics of bands and bonds during a photoinduced phase transition.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {821-825}, doi = {10.1126/science.aar4183}, pmid = {30442808}, issn = {1095-9203}, abstract = {Ultrafast nonequilibrium dynamics offer a route to study the microscopic interactions that govern macroscopic behavior. In particular, photoinduced phase transitions (PIPTs) in solids provide a test case for how forces, and the resulting atomic motion along a reaction coordinate, originate from a nonequilibrium population of excited electronic states. Using femtosecond photoemission, we obtain access to the transient electronic structure during an ultrafast PIPT in a model system: indium nanowires on a silicon(111) surface. We uncover a detailed reaction pathway, allowing a direct comparison with the dynamics predicted by ab initio simulations. This further reveals the crucial role played by localized photoholes in shaping the potential energy landscape and enables a combined momentum- and real-space description of PIPTs, including the ultrafast formation of chemical bonds.}, } @article {pmid30442807, year = {2018}, author = {Lee, JS and Choi, SH and Yun, SJ and Kim, YI and Boandoh, S and Park, JH and Shin, BG and Ko, H and Lee, SH and Kim, YM and Lee, YH and Kim, KK and Kim, SM}, title = {Wafer-scale single-crystal hexagonal boron nitride film via self-collimated grain formation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {817-821}, doi = {10.1126/science.aau2132}, pmid = {30442807}, issn = {1095-9203}, abstract = {Although polycrystalline hexagonal boron nitride (PC-hBN) has been realized, defects and grain boundaries still cause charge scatterings and trap sites, impeding high-performance electronics. Here, we report a method of synthesizing wafer-scale single-crystalline hBN (SC-hBN) monolayer films by chemical vapor deposition. The limited solubility of boron (B) and nitrogen (N) atoms in liquid gold promotes high diffusion of adatoms on the surface of liquid at high temperature to provoke the circular hBN grains. These further evolve into closely packed unimodal grains by means of self-collimation of B and N edges inherited by electrostatic interaction between grains, eventually forming an SC-hBN film on a wafer scale. This SC-hBN film also allows for the synthesis of wafer-scale graphene/hBN heterostructure and single-crystalline tungsten disulfide.}, } @article {pmid30442806, year = {2018}, author = {Guo, J and Suástegui, M and Sakimoto, KK and Moody, VM and Xiao, G and Nocera, DG and Joshi, NS}, title = {Light-driven fine chemical production in yeast biohybrids.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {813-816}, pmid = {30442806}, issn = {1095-9203}, support = {R01 DK110770/DK/NIDDK NIH HHS/United States ; R01 GM047274/GM/NIGMS NIH HHS/United States ; }, abstract = {Inorganic-biological hybrid systems have potential to be sustainable, efficient, and versatile chemical synthesis platforms by integrating the light-harvesting properties of semiconductors with the synthetic potential of biological cells. We have developed a modular bioinorganic hybrid platform that consists of highly efficient light-harvesting indium phosphide nanoparticles and genetically engineered Saccharomyces cerevisiae, a workhorse microorganism in biomanufacturing. The yeast harvests photogenerated electrons from the illuminated nanoparticles and uses them for the cytosolic regeneration of redox cofactors. This process enables the decoupling of biosynthesis and cofactor regeneration, facilitating a carbon- and energy-efficient production of the metabolite shikimic acid, a common precursor for several drugs and fine chemicals. Our work provides a platform for the rational design of biohybrids for efficient biomanufacturing processes with higher complexity and functionality.}, } @article {pmid30442805, year = {2018}, author = {Cheng, KCK and Bedolla-Pantoja, MA and Kim, YK and Gregory, JV and Xie, F and de France, A and Hussal, C and Sun, K and Abbott, NL and Lahann, J}, title = {Templated nanofiber synthesis via chemical vapor polymerization into liquid crystalline films.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {804-808}, doi = {10.1126/science.aar8449}, pmid = {30442805}, issn = {1095-9203}, abstract = {Extrusion, electrospinning, and microdrawing are widely used to create fibrous polymer mats, but these approaches offer limited access to oriented arrays of nanometer-scale fibers with controlled size, shape, and lateral organization. We show that chemical vapor polymerization can be performed on surfaces coated with thin films of liquid crystals to synthesize organized assemblies of end-attached polymer nanofibers. The process uses low concentrations of radical monomers formed initially in the vapor phase and then diffused into the liquid-crystal template. This minimizes monomer-induced changes to the liquid-crystal phase and enables access to nanofiber arrays with complex yet precisely defined structures and compositions. The nanofiber arrays permit tailoring of a wide range of functional properties, including adhesion that depends on nanofiber chirality.}, } @article {pmid30442804, year = {2018}, author = {Hilton, MC and Zhang, X and Boyle, BT and Alegre-Requena, JV and Paton, RS and McNally, A}, title = {Heterobiaryl synthesis by contractive C-C coupling via P(V) intermediates.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {799-804}, doi = {10.1126/science.aas8961}, pmid = {30442804}, issn = {1095-9203}, support = {R01 GM124094/GM/NIGMS NIH HHS/United States ; }, abstract = {Heterobiaryls composed of pyridine and diazine rings are key components of pharmaceuticals and are often central to pharmacological function. We present an alternative approach to metal-catalyzed cross-coupling to make heterobiaryls using contractive phosphorus C-C couplings, also termed phosphorus ligand coupling reactions. The process starts by regioselective phosphorus substitution of the C-H bonds para to nitrogen in two successive heterocycles; ligand coupling is then triggered via acidic alcohol solutions to form the heterobiaryl bond. Mechanistic studies imply that ligand coupling is an asynchronous process involving migration of one heterocycle to the ipso position of the other around a central pentacoordinate P(V) atom. The strategy can be applied to complex drug-like molecules containing multiple reactive sites and polar functional groups, and also enables convergent coupling of drug fragments and late-stage heteroarylation of pharmaceuticals.}, } @article {pmid30442803, year = {2018}, author = {Burke, LM and Hawley, JA}, title = {Swifter, higher, stronger: What's on the menu?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {781-787}, doi = {10.1126/science.aau2093}, pmid = {30442803}, issn = {1095-9203}, abstract = {The exploits of elite athletes delight, frustrate, and confound us as they strive to reach their physiological, psychological, and biomechanical limits. We dissect nutritional approaches to optimal performance, showcasing the contribution of modern sports science to gold medals and world titles. Despite an enduring belief in a single, superior "athletic diet," diversity in sports nutrition practices among successful athletes arises from the specificity of the metabolic demands of different sports and the periodization of training and competition goals. Pragmatic implementation of nutrition strategies in real-world scenarios and the prioritization of important strategies when nutrition themes are in conflict add to this variation. Lastly, differences in athlete practices both promote and reflect areas of controversy and disagreement among sports nutrition experts.}, } @article {pmid30442802, year = {2018}, author = {Gentile, CL and Weir, TL}, title = {The gut microbiota at the intersection of diet and human health.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {776-780}, doi = {10.1126/science.aau5812}, pmid = {30442802}, issn = {1095-9203}, abstract = {Diet affects multiple facets of human health and is inextricably linked to chronic metabolic conditions such as obesity, type 2 diabetes, and cardiovascular disease. Dietary nutrients are essential not only for human health but also for the health and survival of the trillions of microbes that reside within the human intestines. Diet is a key component of the relationship between humans and their microbial residents; gut microbes use ingested nutrients for fundamental biological processes, and the metabolic outputs of those processes may have important impacts on human physiology. Studies in humans and animal models are beginning to unravel the underpinnings of this relationship, and increasing evidence suggests that it may underlie some of the broader effects of diet on human health and disease.}, } @article {pmid30442801, year = {2018}, author = {Di Francesco, A and Di Germanio, C and Bernier, M and de Cabo, R}, title = {A time to fast.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {770-775}, doi = {10.1126/science.aau2095}, pmid = {30442801}, issn = {1095-9203}, abstract = {Nutrient composition and caloric intake have traditionally been used to devise optimized diets for various phases of life. Adjustment of meal size and frequency have emerged as powerful tools to ameliorate and postpone the onset of disease and delay aging, whereas periods of fasting, with or without reduced energy intake, can have profound health benefits. The underlying physiological processes involve periodic shifts of metabolic fuel sources, promotion of repair mechanisms, and the optimization of energy utilization for cellular and organismal health. Future research endeavors should be directed to the integration of a balanced nutritious diet with controlled meal size and patterns and periods of fasting to develop better strategies to prevent, postpone, and treat the socioeconomical burden of chronic diseases associated with aging.}, } @article {pmid30442800, year = {2018}, author = {Ludwig, DS and Willett, WC and Volek, JS and Neuhouser, ML}, title = {Dietary fat: From foe to friend?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {764-770}, doi = {10.1126/science.aau2096}, pmid = {30442800}, issn = {1095-9203}, support = {K24 DK082730/DK/NIDDK NIH HHS/United States ; }, abstract = {For decades, dietary advice was based on the premise that high intakes of fat cause obesity, diabetes, heart disease, and possibly cancer. Recently, evidence for the adverse metabolic effects of processed carbohydrate has led to a resurgence in interest in lower-carbohydrate and ketogenic diets with high fat content. However, some argue that the relative quantity of dietary fat and carbohydrate has little relevance to health and that focus should instead be placed on which particular fat or carbohydrate sources are consumed. This review, by nutrition scientists with widely varying perspectives, summarizes existing evidence to identify areas of broad consensus amid ongoing controversy regarding macronutrients and chronic disease.}, } @article {pmid30442799, year = {2018}, author = {Ray, LB}, title = {Optimizing the diet.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {762-763}, doi = {10.1126/science.aav9415}, pmid = {30442799}, issn = {1095-9203}, } @article {pmid30442798, year = {2018}, author = {}, title = {NextGen VOICES: Transition challenges.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {760}, doi = {10.1126/science.362.6416.760}, pmid = {30442798}, issn = {1095-9203}, } @article {pmid30442797, year = {2018}, author = {Botkin, JR and Appelbaum, PS and Bakken, S and Brown, C and Burke, W and Fabsitz, R and Gamble, VN and Gonsalves, G and Kost, R and Leonard, DGB and McGuire, A and Nichols, JH and Patrick-Lake, B and Wilkins, CH and Zikmund-Fisher, BJ}, title = {Standardizing return of participant results.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {759-760}, doi = {10.1126/science.aav8095}, pmid = {30442797}, issn = {1095-9203}, } @article {pmid30442796, year = {2018}, author = {Valdés-Sosa, MJ and Foster, KR}, title = {Halt speculation on U.S. embassy in Cuba.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {758-759}, doi = {10.1126/science.aav5485}, pmid = {30442796}, issn = {1095-9203}, } @article {pmid30442795, year = {2018}, author = {Klein, T and Hartmann, H}, title = {Climate change drives tree mortality.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {758}, doi = {10.1126/science.aav6508}, pmid = {30442795}, issn = {1095-9203}, mesh = {*Climate Change ; Droughts ; Forests ; *Trees ; }, } @article {pmid30442794, year = {2018}, author = {Crowley, M and Shang, L and Dando, M}, title = {Preventing chemical weapons as sciences converge.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {753-755}, doi = {10.1126/science.aav5129}, pmid = {30442794}, issn = {1095-9203}, } @article {pmid30442792, year = {2018}, author = {Martínez, A}, title = {Polarimetry enabled by nanophotonics.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {750-751}, doi = {10.1126/science.aau7494}, pmid = {30442792}, issn = {1095-9203}, } @article {pmid30442791, year = {2018}, author = {Tasic, B and Nicovich, PR}, title = {Cell types behaving in their natural habitat.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {749-750}, doi = {10.1126/science.aav4841}, pmid = {30442791}, issn = {1095-9203}, } @article {pmid30442790, year = {2018}, author = {Samson, LD}, title = {A target to suppress inflammation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {748-749}, doi = {10.1126/science.aav4744}, pmid = {30442790}, issn = {1095-9203}, } @article {pmid30442789, year = {2018}, author = {Dejana, E and Lampugnani, MG}, title = {Endothelial cell transitions.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {746-747}, doi = {10.1126/science.aas9432}, pmid = {30442789}, issn = {1095-9203}, } @article {pmid30442788, year = {2018}, author = {Gaston, KJ}, title = {Lighting up the nighttime.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {744-746}, doi = {10.1126/science.aau8226}, pmid = {30442788}, issn = {1095-9203}, } @article {pmid30442787, year = {2018}, author = {Voosen, P}, title = {Ice age impact.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {738-742}, doi = {10.1126/science.362.6416.738}, pmid = {30442787}, issn = {1095-9203}, } @article {pmid30442786, year = {2018}, author = {Mann, A}, title = {Large galaxy found lurking on the Milky Way's far side.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {737}, doi = {10.1126/science.362.6416.737}, pmid = {30442786}, issn = {1095-9203}, } @article {pmid30442785, year = {2018}, author = {Servick, K}, title = {Reprogrammed cells could tackle brain damage.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {736-737}, doi = {10.1126/science.362.6416.736}, pmid = {30442785}, issn = {1095-9203}, } @article {pmid30442784, year = {2018}, author = {Vogel, G}, title = {Fresh fights roil evidence-based medicine group.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {735}, doi = {10.1126/science.362.6416.735}, pmid = {30442784}, issn = {1095-9203}, } @article {pmid30442783, year = {2018}, author = {Kaiser, J}, title = {Obesity gives unexpected boost to anticancer drugs.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {734}, doi = {10.1126/science.362.6416.734}, pmid = {30442783}, issn = {1095-9203}, } @article {pmid30442782, year = {2018}, author = {Gibbons, A}, title = {Eruption made 536 'the worst year to be alive'.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {733-734}, doi = {10.1126/science.362.6416.733}, pmid = {30442782}, issn = {1095-9203}, } @article {pmid30442781, year = {2018}, author = {Mervis, J}, title = {Vote heralds fresh start for science panel.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {731-732}, doi = {10.1126/science.362.6416.731}, pmid = {30442781}, issn = {1095-9203}, } @article {pmid30442780, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {728-730}, doi = {10.1126/science.362.6416.728}, pmid = {30442780}, issn = {1095-9203}, } @article {pmid30442779, year = {2018}, author = {Horvat, M}, title = {Reform and cooperation in China.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {727}, doi = {10.1126/science.aav9737}, pmid = {30442779}, issn = {1095-9203}, } @article {pmid30442778, year = {2018}, author = {Kory, N and Wyant, GA and Prakash, G and Uit de Bos, J and Bottanelli, F and Pacold, ME and Chan, SH and Lewis, CA and Wang, T and Keys, HR and Guo, YE and Sabatini, DM}, title = {SFXN1 is a mitochondrial serine transporter required for one-carbon metabolism.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {}, doi = {10.1126/science.aat9528}, pmid = {30442778}, issn = {1095-9203}, support = {R01 CA103866/CA/NCI NIH HHS/United States ; R01 CA129105/CA/NCI NIH HHS/United States ; R37 AI047389/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {One-carbon metabolism generates the one-carbon units required to synthesize many critical metabolites, including nucleotides. The pathway has cytosolic and mitochondrial branches, and a key step is the entry, through an unknown mechanism, of serine into mitochondria, where it is converted into glycine and formate. In a CRISPR-based genetic screen in human cells for genes of the mitochondrial pathway, we found sideroflexin 1 (SFXN1), a multipass inner mitochondrial membrane protein of unclear function. Like cells missing mitochondrial components of one-carbon metabolism, those null for SFXN1 are defective in glycine and purine synthesis. Cells lacking SFXN1 and one of its four homologs, SFXN3, have more severe defects, including being auxotrophic for glycine. Purified SFXN1 transports serine in vitro. Thus, SFXN1 functions as a mitochondrial serine transporter in one-carbon metabolism.}, } @article {pmid30442777, year = {2018}, author = {Estrada, JG and Ahneman, DT and Sheridan, RP and Dreher, SD and Doyle, AG}, title = {Response to Comment on "Predicting reaction performance in C-N cross-coupling using machine learning".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {}, doi = {10.1126/science.aat8763}, pmid = {30442777}, issn = {1095-9203}, mesh = {*Machine Learning ; *Models, Chemical ; }, abstract = {We demonstrate that the chemical-feature model described in our original paper is distinguishable from the nongeneralizable models introduced by Chuang and Keiser. Furthermore, the chemical-feature model significantly outperforms these models in out-of-sample predictions, justifying the use of chemical featurization from which machine learning models can extract meaningful patterns in the dataset, as originally described.}, } @article {pmid30442776, year = {2018}, author = {Chuang, KV and Keiser, MJ}, title = {Comment on "Predicting reaction performance in C-N cross-coupling using machine learning".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {}, doi = {10.1126/science.aat8603}, pmid = {30442776}, issn = {1095-9203}, abstract = {Ahneman et al (Reports, 13 April 2018) applied machine learning models to predict C-N cross-coupling reaction yields. The models use atomic, electronic, and vibrational descriptors as input features. However, the experimental design is insufficient to distinguish models trained on chemical features from those trained solely on random-valued features in retrospective and prospective test scenarios, thus failing classical controls in machine learning.}, } @article {pmid30442767, year = {2018}, author = {Torbert, RB and Burch, JL and Phan, TD and Hesse, M and Argall, MR and Shuster, J and Ergun, RE and Alm, L and Nakamura, R and Genestreti, KJ and Gershman, DJ and Paterson, WR and Turner, DL and Cohen, I and Giles, BL and Pollock, CJ and Wang, S and Chen, LJ and Stawarz, JE and Eastwood, JP and Hwang, KJ and Farrugia, C and Dors, I and Vaith, H and Mouikis, C and Ardakani, A and Mauk, BH and Fuselier, SA and Russell, CT and Strangeway, RJ and Moore, TE and Drake, JF and Shay, MA and Khotyaintsev, YV and Lindqvist, PA and Baumjohann, W and Wilder, FD and Ahmadi, N and Dorelli, JC and Avanov, LA and Oka, M and Baker, DN and Fennell, JF and Blake, JB and Jaynes, AN and Le Contel, O and Petrinec, SM and Lavraud, B and Saito, Y}, title = {Electron-scale dynamics of the diffusion region during symmetric magnetic reconnection in space.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1391-1395}, doi = {10.1126/science.aat2998}, pmid = {30442767}, issn = {1095-9203}, abstract = {Magnetic reconnection is an energy conversion process that occurs in many astrophysical contexts including Earth's magnetosphere, where the process can be investigated in situ by spacecraft. On 11 July 2017, the four Magnetospheric Multiscale spacecraft encountered a reconnection site in Earth's magnetotail, where reconnection involves symmetric inflow conditions. The electron-scale plasma measurements revealed (i) super-Alfvénic electron jets reaching 15,000 kilometers per second; (ii) electron meandering motion and acceleration by the electric field, producing multiple crescent-shaped structures in the velocity distributions; and (iii) the spatial dimensions of the electron diffusion region with an aspect ratio of 0.1 to 0.2, consistent with fast reconnection. The well-structured multiple layers of electron populations indicate that the dominant electron dynamics are mostly laminar, despite the presence of turbulence near the reconnection site.}, } @article {pmid30442766, year = {2018}, author = {Bigenzahn, JW and Collu, GM and Kartnig, F and Pieraks, M and Vladimer, GI and Heinz, LX and Sedlyarov, V and Schischlik, F and Fauster, A and Rebsamen, M and Parapatics, K and Blomen, VA and Müller, AC and Winter, GE and Kralovics, R and Brummelkamp, TR and Mlodzik, M and Superti-Furga, G}, title = {LZTR1 is a regulator of RAS ubiquitination and signaling.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1171-1177}, doi = {10.1126/science.aap8210}, pmid = {30442766}, issn = {1095-9203}, support = {R01 EY013256/EY/NEI NIH HHS/United States ; R01 GM102811/GM/NIGMS NIH HHS/United States ; }, abstract = {In genetic screens aimed at understanding drug resistance mechanisms in chronic myeloid leukemia cells, inactivation of the cullin 3 adapter protein-encoding leucine zipper-like transcription regulator 1 (LZTR1) gene led to enhanced mitogen-activated protein kinase (MAPK) pathway activity and reduced sensitivity to tyrosine kinase inhibitors. Knockdown of the Drosophila LZTR1 ortholog CG3711 resulted in a Ras-dependent gain-of-function phenotype. Endogenous human LZTR1 associates with the main RAS isoforms. Inactivation of LZTR1 led to decreased ubiquitination and enhanced plasma membrane localization of endogenous KRAS (V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog). We propose that LZTR1 acts as a conserved regulator of RAS ubiquitination and MAPK pathway activation. Because LZTR1 disease mutations failed to revert loss-of-function phenotypes, our findings provide a molecular rationale for LZTR1 involvement in a variety of inherited and acquired human disorders.}, } @article {pmid30442765, year = {2018}, author = {Díaz-Santos, T and Assef, RJ and Blain, AW and Aravena, M and Stern, D and Tsai, CW and Eisenhardt, P and Wu, J and Jun, HD and Dibert, K and Inami, H and Lansbury, G and Leclercq, F}, title = {The multiple merger assembly of a hyperluminous obscured quasar at redshift 4.6.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1034-1036}, doi = {10.1126/science.aap7605}, pmid = {30442765}, issn = {1095-9203}, abstract = {Galaxy mergers and gas accretion from the cosmic web drove the growth of galaxies and their central black holes at early epochs. We report spectroscopic imaging of a multiple merger event in the most luminous known galaxy, WISE J224607.56-052634.9 (W2246-0526), a dust-obscured quasar at redshift 4.6, 1.3 billion years after the Big Bang. Far-infrared dust continuum observations show three galaxy companions around W2246-0526 with disturbed morphologies, connected by streams of dust likely produced by the dynamical interaction. The detection of tidal dusty bridges shows that W2246-0526 is accreting its neighbors, suggesting that merger activity may be a dominant mechanism through which the most luminous galaxies simultaneously obscure and feed their central supermassive black holes.}, } @article {pmid30442764, year = {2018}, author = {Patel, AB and Louder, RK and Greber, BJ and Grünberg, S and Luo, J and Fang, J and Liu, Y and Ranish, J and Hahn, S and Nogales, E}, title = {Structure of human TFIID and mechanism of TBP loading onto promoter DNA.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {}, doi = {10.1126/science.aau8872}, pmid = {30442764}, issn = {1095-9203}, support = {R01 GM063072/GM/NIGMS NIH HHS/United States ; R01 GM053451/GM/NIGMS NIH HHS/United States ; P50 GM076547/GM/NIGMS NIH HHS/United States ; R21 CA175849/CA/NCI NIH HHS/United States ; T32 GM008295/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {The general transcription factor IID (TFIID) is a critical component of the eukaryotic transcription preinitiation complex (PIC) and is responsible for recognizing the core promoter DNA and initiating PIC assembly. We used cryo-electron microscopy, chemical cross-linking mass spectrometry, and biochemical reconstitution to determine the complete molecular architecture of TFIID and define the conformational landscape of TFIID in the process of TATA box-binding protein (TBP) loading onto promoter DNA. Our structural analysis revealed five structural states of TFIID in the presence of TFIIA and promoter DNA, showing that the initial binding of TFIID to the downstream promoter positions the upstream DNA and facilitates scanning of TBP for a TATA box and the subsequent engagement of the promoter. Our findings provide a mechanistic model for the specific loading of TBP by TFIID onto the promoter.}, } @article {pmid30442763, year = {2018}, author = {Bunting, PC and Atanasov, M and Damgaard-Møller, E and Perfetti, M and Crassee, I and Orlita, M and Overgaard, J and van Slageren, J and Neese, F and Long, JR}, title = {A linear cobalt(II) complex with maximal orbital angular momentum from a non-Aufbau ground state.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {}, doi = {10.1126/science.aat7319}, pmid = {30442763}, issn = {1095-9203}, abstract = {Orbital angular momentum is a prerequisite for magnetic anisotropy, although in transition metal complexes it is typically quenched by the ligand field. By reducing the basicity of the carbon donor atoms in a pair of alkyl ligands, we synthesized a cobalt(II) dialkyl complex, Co(C(SiMe2ONaph)3)2 (where Me is methyl and Naph is a naphthyl group), wherein the ligand field is sufficiently weak that interelectron repulsion and spin-orbit coupling play a dominant role in determining the electronic ground state. Assignment of a non-Aufbau (d x 2 -y 2 , d xy)3(d xz , d yz)3(d z 2)1 electron configuration is supported by dc magnetic susceptibility data, experimental charge density maps, and ab initio calculations. Variable-field far-infrared spectroscopy and ac magnetic susceptibility measurements further reveal slow magnetic relaxation via a 450-wave number magnetic excited state.}, } @article {pmid30442762, year = {2018}, author = {Steklov, M and Pandolfi, S and Baietti, MF and Batiuk, A and Carai, P and Najm, P and Zhang, M and Jang, H and Renzi, F and Cai, Y and Abbasi Asbagh, L and Pastor, T and De Troyer, M and Simicek, M and Radaelli, E and Brems, H and Legius, E and Tavernier, J and Gevaert, K and Impens, F and Messiaen, L and Nussinov, R and Heymans, S and Eyckerman, S and Sablina, AA}, title = {Mutations in LZTR1 drive human disease by dysregulating RAS ubiquitination.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1177-1182}, doi = {10.1126/science.aap7607}, pmid = {30442762}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The leucine zipper-like transcriptional regulator 1 (LZTR1) protein, an adaptor for cullin 3 (CUL3) ubiquitin ligase complex, is implicated in human disease, yet its mechanism of action remains unknown. We found that Lztr1 haploinsufficiency in mice recapitulates Noonan syndrome phenotypes, whereas LZTR1 loss in Schwann cells drives dedifferentiation and proliferation. By trapping LZTR1 complexes from intact mammalian cells, we identified the guanosine triphosphatase RAS as a substrate for the LZTR1-CUL3 complex. Ubiquitome analysis showed that loss of Lztr1 abrogated Ras ubiquitination at lysine-170. LZTR1-mediated ubiquitination inhibited RAS signaling by attenuating its association with the membrane. Disease-associated LZTR1 mutations disrupted either LZTR1-CUL3 complex formation or its interaction with RAS proteins. RAS regulation by LZTR1-mediated ubiquitination provides an explanation for the role of LZTR1 in human disease.}, } @article {pmid30442672, year = {2018}, author = {Lefebvre, G and Nioche, A and Bourgeois-Gironde, S and Palminteri, S}, title = {Contrasting temporal difference and opportunity cost reinforcement learning in an empirical money-emergence paradigm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11446-E11454}, doi = {10.1073/pnas.1813197115}, pmid = {30442672}, issn = {1091-6490}, abstract = {Money is a fundamental and ubiquitous institution in modern economies. However, the question of its emergence remains a central one for economists. The monetary search-theoretic approach studies the conditions under which commodity money emerges as a solution to override frictions inherent to interindividual exchanges in a decentralized economy. Although among these conditions, agents' rationality is classically essential and a prerequisite to any theoretical monetary equilibrium, human subjects often fail to adopt optimal strategies in tasks implementing a search-theoretic paradigm when these strategies are speculative, i.e., involve the use of a costly medium of exchange to increase the probability of subsequent and successful trades. In the present work, we hypothesize that implementing such speculative behaviors relies on reinforcement learning instead of lifetime utility calculations, as supposed by classical economic theory. To test this hypothesis, we operationalized the Kiyotaki and Wright paradigm of money emergence in a multistep exchange task and fitted behavioral data regarding human subjects performing this task with two reinforcement learning models. Each of them implements a distinct cognitive hypothesis regarding the weight of future or counterfactual rewards in current decisions. We found that both models outperformed theoretical predictions about subjects' behaviors regarding the implementation of speculative strategies and that the latter relies on the degree of the opportunity costs consideration in the learning process. Speculating about the marketability advantage of money thus seems to depend on mental simulations of counterfactual events that agents are performing in exchange situations.}, } @article {pmid30442671, year = {2018}, author = {Bor, B and McLean, JS and Foster, KR and Cen, L and To, TT and Serrato-Guillen, A and Dewhirst, FE and Shi, W and He, X}, title = {Rapid evolution of decreased host susceptibility drives a stable relationship between ultrasmall parasite TM7x and its bacterial host.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12277-12282}, pmid = {30442671}, issn = {1091-6490}, support = {R01 DE023810/DE/NIDCR NIH HHS/United States ; R01 DE026186/DE/NIDCR NIH HHS/United States ; R01 DE024468/DE/NIDCR NIH HHS/United States ; F32 DE025548/DE/NIDCR NIH HHS/United States ; K99 DE027719/DE/NIDCR NIH HHS/United States ; R37 DE016937/DE/NIDCR NIH HHS/United States ; R01 DE020102/DE/NIDCR NIH HHS/United States ; T90 DE022734/DE/NIDCR NIH HHS/United States ; }, abstract = {Around one-quarter of bacterial diversity comprises a single radiation with reduced genomes, known collectively as the Candidate Phyla Radiation. Recently, we coisolated TM7x, an ultrasmall strain of the Candidate Phyla Radiation phylum Saccharibacteria, with its bacterial host Actinomyces odontolyticus strain XH001 from human oral cavity and stably maintained as a coculture. Our current work demonstrates that within the coculture, TM7x cells establish a long-term parasitic association with host cells by infecting only a subset of the population, which stay viable yet exhibit severely inhibited cell division. In contrast, exposure of a naïve A. odontolyticus isolate, XH001n, to TM7x cells leads to high numbers of TM7x cells binding to each host cell, massive host cell death, and a host population crash. However, further passaging reveals that XH001n becomes less susceptible to TM7x over time and enters a long-term stable relationship similar to that of XH001. We show that this reduced susceptibility is driven by rapid host evolution that, in contrast to many forms of phage resistance, offers only partial protection. The result is a stalemate where infected hosts cannot shed their parasites; nevertheless, parasite load is sufficiently low that the host population persists. Finally, we show that TM7x can infect and form stable long-term relationships with other species in a single clade of Actinomyces, displaying a narrow host range. This system serves as a model to understand how parasitic bacteria with reduced genomes such as those of the Candidate Phyla Radiation have persisted with their hosts and ultimately expanded in their diversity.}, } @article {pmid30442670, year = {2018}, author = {Gao, X and Castro-Gomez, S and Grendel, J and Graf, S and Süsens, U and Binkle, L and Mensching, D and Isbrandt, D and Kuhl, D and Ohana, O}, title = {Arc/Arg3.1 mediates a critical period for spatial learning and hippocampal networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12531-12536}, doi = {10.1073/pnas.1810125115}, pmid = {30442670}, issn = {1091-6490}, abstract = {During early postnatal development, sensory regions of the brain undergo periods of heightened plasticity which sculpt neural networks and lay the foundation for adult sensory perception. Such critical periods were also postulated for learning and memory but remain elusive and poorly understood. Here, we present evidence that the activity-regulated and memory-linked gene Arc/Arg3.1 is transiently up-regulated in the hippocampus during the first postnatal month. Conditional removal of Arc/Arg3.1 during this period permanently alters hippocampal oscillations and diminishes spatial learning capacity throughout adulthood. In contrast, post developmental removal of Arc/Arg3.1 leaves learning and network activity patterns intact. Long-term memory storage continues to rely on Arc/Arg3.1 expression throughout life. These results demonstrate that Arc/Arg3.1 mediates a critical period for spatial learning, during which Arc/Arg3.1 fosters maturation of hippocampal network activity necessary for future learning and memory storage.}, } @article {pmid30442669, year = {2018}, author = {Paschalis, EI and Lei, F and Zhou, C and Kapoulea, V and Dana, R and Chodosh, J and Vavvas, DG and Dohlman, CH}, title = {Permanent neuroglial remodeling of the retina following infiltration of CSF1R inhibition-resistant peripheral monocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11359-E11368}, pmid = {30442669}, issn = {1091-6490}, support = {P30 EY003790/EY/NEI NIH HHS/United States ; P30 EY014104/EY/NEI NIH HHS/United States ; R01 EY025362/EY/NEI NIH HHS/United States ; R21 EY023079/EY/NEI NIH HHS/United States ; }, abstract = {Previous studies have demonstrated that ocular injury can lead to prompt infiltration of bone-marrow-derived peripheral monocytes into the retina. However, the ability of these cells to integrate into the tissue and become microglia has not been investigated. Here we show that such peripheral monocytes that infiltrate into the retina after ocular injury engraft permanently, migrate to the three distinct microglia strata, and adopt a microglia-like morphology. In the absence of ocular injury, peripheral monocytes that repopulate the retina after depletion with colony-stimulating factor 1 receptor (CSF1R) inhibitor remain sensitive to CSF1R inhibition and can be redepleted. Strikingly, consequent to ocular injury, the engrafted peripheral monocytes are resistant to depletion by CSF1R inhibitor and likely express low CSF1R. Moreover, these engrafted monocytes remain proinflammatory, expressing high levels of MHC-II, IL-1β, and TNF-α over the long term. The observed permanent neuroglia remodeling after injury constitutes a major immunological change that may contribute to progressive retinal degeneration. These findings may also be relevant to other degenerative conditions of the retina and the central nervous system.}, } @article {pmid30442668, year = {2018}, author = {Lin, H and Gao, D and Hu, MM and Zhang, M and Wu, XX and Feng, L and Xu, WH and Yang, Q and Zhong, X and Wei, J and Xu, ZS and Zhang, HX and Song, ZM and Zhou, Q and Ye, W and Liu, Y and Li, S and Shu, HB}, title = {MARCH3 attenuates IL-1β-triggered inflammation by mediating K48-linked polyubiquitination and degradation of IL-1RI.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12483-12488}, doi = {10.1073/pnas.1806217115}, pmid = {30442668}, issn = {1091-6490}, abstract = {The proinflammatory cytokine IL-1β plays critical roles in inflammatory and autoimmune diseases. IL-1β signaling is tightly regulated to avoid excessive inflammatory response. In this study, we identified the E3 ubiquitin ligase membrane-associated RING-CH-type finger 3 (MARCH3) as a critical negative regulator of IL-1β-triggered signaling. Overexpression of MARCH3 inhibited IL-1β-triggered activation of NF-κB as well as expression of inflammatory genes, whereas MARCH3 deficiency had the opposite effects. MARCH3-deficient mice produced higher levels of serum inflammatory cytokines and were more sensitive to inflammatory death upon IL-1β injection or Listeria monocytogenes infection. Mechanistically, MARCH3 was associated with IL-1 receptor I (IL-1RI) and mediated its K48-linked polyubiquitination at K409 and lysosomal-dependent degradation. Furthermore, IL-1β stimulation triggered dephosphorylation of MARCH3 by CDC25A and activation of its E3 ligase activity. Our findings suggest that MARCH3-mediated IL-1RI degradation is an important mechanism for attenuating IL-1β-triggered inflammatory response.}, } @article {pmid30442667, year = {2018}, author = {Dias, J and Boulouis, C and Gorin, JB and van den Biggelaar, RHGA and Lal, KG and Gibbs, A and Loh, L and Gulam, MY and Sia, WR and Bari, S and Hwang, WYK and Nixon, DF and Nguyen, S and Betts, MR and Buggert, M and Eller, MA and Broliden, K and Tjernlund, A and Sandberg, JK and Leeansyah, E}, title = {The CD4-CD8- MAIT cell subpopulation is a functionally distinct subset developmentally related to the main CD8+ MAIT cell pool.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11513-E11522}, doi = {10.1073/pnas.1812273115}, pmid = {30442667}, issn = {1091-6490}, support = {R01 DK108350/DK/NIDDK NIH HHS/United States ; }, abstract = {Mucosa-associated invariant T (MAIT) cells are unconventional innate-like T cells that recognize microbial riboflavin metabolites presented by the MHC class I-like protein MR1. Human MAIT cells predominantly express the CD8α coreceptor (CD8+), with a smaller subset lacking both CD4 and CD8 (double-negative, DN). However, it is unclear if these two MAIT cell subpopulations distinguished by CD8α represent functionally distinct subsets. Here, we show that the two MAIT cell subsets express divergent transcriptional programs and distinct patterns of classic T cell transcription factors. Furthermore, CD8+ MAIT cells have higher levels of receptors for IL-12 and IL-18, as well as of the activating receptors CD2, CD9, and NKG2D, and display superior functionality following stimulation with riboflavin-autotrophic as well as riboflavin-auxotrophic bacterial strains. DN MAIT cells display higher RORγt/T-bet ratio, and express less IFN-γ and more IL-17. Furthermore, the DN subset displays enrichment of an apoptosis gene signature and higher propensity for activation-induced apoptosis. During development in human fetal tissues, DN MAIT cells are more mature and accumulate over gestational time with reciprocal contraction of the CD8+ subset. Analysis of the T cell receptor repertoire reveals higher diversity in CD8+ MAIT cells than in DN MAIT cells. Finally, chronic T cell receptor stimulation of CD8+ MAIT cells in an in vitro culture system supports the accumulation and maintenance of the DN subpopulation. These findings define human CD8+ and DN MAIT cells as functionally distinct subsets and indicate a derivative developmental relationship.}, } @article {pmid30442666, year = {2018}, author = {McAlpine, W and Sun, L and Wang, KW and Liu, A and Jain, R and San Miguel, M and Wang, J and Zhang, Z and Hayse, B and McAlpine, SG and Choi, JH and Zhong, X and Ludwig, S and Russell, J and Zhan, X and Choi, M and Li, X and Tang, M and Moresco, EMY and Beutler, B and Turer, E}, title = {Excessive endosomal TLR signaling causes inflammatory disease in mice with defective SMCR8-WDR41-C9ORF72 complex function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11523-E11531}, doi = {10.1073/pnas.1814753115}, pmid = {30442666}, issn = {1091-6490}, support = {K08 DK107886/DK/NIDDK NIH HHS/United States ; R01 AI125581/AI/NIAID NIH HHS/United States ; U19 AI100627/AI/NIAID NIH HHS/United States ; R37 GM036659/GM/NIGMS NIH HHS/United States ; }, abstract = {The SMCR8-WDR41-C9ORF72 complex is a regulator of autophagy and lysosomal function. Autoimmunity and inflammatory disease have been ascribed to loss-of-function mutations of Smcr8 or C9orf72 in mice. In humans, autoimmunity has been reported to precede amyotrophic lateral sclerosis caused by mutations of C9ORF72 However, the cellular and molecular mechanisms underlying autoimmunity and inflammation caused by C9ORF72 or SMCR8 deficiencies remain unknown. Here, we show that splenomegaly, lymphadenopathy, and activated circulating T cells observed in Smcr8-/- mice were rescued by triple knockout of the endosomal Toll-like receptors (TLRs) TLR3, TLR7, and TLR9. Myeloid cells from Smcr8-/- mice produced excessive inflammatory cytokines in response to endocytosed TLR3, TLR7, or TLR9 ligands administered in the growth medium and in response to TLR2 or TLR4 ligands internalized by phagocytosis. These defects likely stem from prolonged TLR signaling caused by accumulation of LysoTracker-positive vesicles and by delayed phagosome maturation, both of which were observed in Smcr8-/- macrophages. Smcr8-/- mice also showed elevated susceptibility to dextran sodium sulfate-induced colitis, which was not associated with increased TLR3, TLR7, or TLR9 signaling. Deficiency of WDR41 phenocopied loss of SMCR8. Our findings provide evidence that excessive endosomal TLR signaling resulting from prolonged ligand-receptor contact causes inflammatory disease in SMCR8-deficient mice.}, } @article {pmid30442665, year = {2018}, author = {Hong, L and Vani, BP and Thiede, EH and Rust, MJ and Dinner, AR}, title = {Molecular dynamics simulations of nucleotide release from the circadian clock protein KaiC reveal atomic-resolution functional insights.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11475-E11484}, doi = {10.1073/pnas.1812555115}, pmid = {30442665}, issn = {1091-6490}, support = {R01 GM109455/GM/NIGMS NIH HHS/United States ; R01 EY025957/EY/NEI NIH HHS/United States ; R01 GM107369/GM/NIGMS NIH HHS/United States ; S10 OD018495/OD/NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; }, abstract = {The cyanobacterial clock proteins KaiA, KaiB, and KaiC form a powerful system to study the biophysical basis of circadian rhythms, because an in vitro mixture of the three proteins is sufficient to generate a robust ∼24-h rhythm in the phosphorylation of KaiC. The nucleotide-bound states of KaiC critically affect both KaiB binding to the N-terminal domain (CI) and the phosphotransfer reactions that (de)phosphorylate the KaiC C-terminal domain (CII). However, the nucleotide exchange pathways associated with transitions among these states are poorly understood. In this study, we integrate recent advances in molecular dynamics methods to elucidate the structure and energetics of the pathway for Mg·ADP release from the CII domain. We find that nucleotide release is coupled to large-scale conformational changes in the KaiC hexamer. Solvating the nucleotide requires widening the subunit interface leading to the active site, which is linked to extension of the A-loop, a structure implicated in KaiA binding. These results provide a molecular hypothesis for how KaiA acts as a nucleotide exchange factor. In turn, structural parallels between the CI and CII domains suggest a mechanism for allosteric coupling between the domains. We relate our results to structures observed for other hexameric ATPases, which perform diverse functions.}, } @article {pmid30442664, year = {2018}, author = {Otieno, SA and Hanz, SZ and Chakravorty, B and Zhang, A and Klees, LM and An, M and Qiang, W}, title = {pH-dependent thermodynamic intermediates of pHLIP membrane insertion determined by solid-state NMR spectroscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12194-12199}, pmid = {30442664}, issn = {1091-6490}, abstract = {The applications of the pH low insertion peptide (pHLIP) in cancer diagnosis and cross-membrane cargo delivery have drawn increasing attention in the past decade. With its origin as the transmembrane (TM) helix C of bacteriorhodopsin, pHLIP is also an important model for understanding how pH can affect the folding and topogenesis of a TM α-helix. Protonations of multiple D/E residues transform pHLIP from an unstructured coil at membrane surface (known as state II, at pH ≥ 7) to a TM α-helix (state III, pH ≤ 5.3). While these initial and end states of pHLIP insertion have been firmly established, what happens at the intervening pH values is less clear. However, the intervening pH range is most relevant to pHLIP-cell interactions in the acidic extracellular tumor environment (and in the endosomes within cells). Here, using advanced solid-state NMR spectroscopy with palmitoyl-2-oleoyl-sn-glycerol-3-phosphocholine unilamellar vesicles as the model membrane, we systematically examined the state of pHLIP-membrane interactions (in terms of the membrane locations of D/E residues, as well as lipid dynamics) at the intervening pH values of 6.4, 6.1, and 5.8, along with the known states at pH 7.4 and 5.3. Thermodynamic intermediate states distinct from the initial and end states were discovered to exist at each of the intervening pH examined. They support a multistage model of pHLIP insertion in which the D/E titrations occur in a defined sequence at distinct intermediate pH values. This multistage model has important ramifications in pHLIP applications.}, } @article {pmid30442663, year = {2018}, author = {Shen, H and Marino, RAM and McDevitt, RA and Bi, GH and Chen, K and Madeo, G and Lee, PT and Liang, Y and De Biase, LM and Su, TP and Xi, ZX and Bonci, A}, title = {Genetic deletion of vesicular glutamate transporter in dopamine neurons increases vulnerability to MPTP-induced neurotoxicity in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11532-E11541}, doi = {10.1073/pnas.1800886115}, pmid = {30442663}, issn = {1091-6490}, abstract = {A subset of midbrain dopamine (DA) neurons express vesicular glutamate transporter 2 (VgluT2), which facilitates synaptic vesicle loading of glutamate. Recent studies indicate that such expression can modulate DA-dependent reward behaviors, but little is known about functional consequences of DA neuron VgluT2 expression in neurodegenerative diseases like Parkinson's disease (PD). Here, we report that selective deletion of VgluT2 in DA neurons in conditional VgluT2-KO (VgluT2-cKO) mice abolished glutamate release from DA neurons, reduced their expression of brain-derived neurotrophic factor (BDNF) and tyrosine receptor kinase B (TrkB), and exacerbated the pathological effects of exposure to the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Furthermore, viral rescue of VgluT2 expression in DA neurons of VglutT2-cKO mice restored BDNF/TrkB expression and attenuated MPTP-induced DA neuron loss and locomotor impairment. Together, these findings indicate that VgluT2 expression in DA neurons is neuroprotective. Genetic or environmental factors causing reduced expression or function of VgluT2 in DA neurons may place some individuals at increased risk for DA neuron degeneration. Therefore, maintaining physiological expression and function of VgluT2 in DA neurons may represent a valid molecular target for the development of preventive therapeutic interventions for PD.}, } @article {pmid30442662, year = {2018}, author = {Alexander, EJ and Ghanbari Niaki, A and Zhang, T and Sarkar, J and Liu, Y and Nirujogi, RS and Pandey, A and Myong, S and Wang, J}, title = {Ubiquilin 2 modulates ALS/FTD-linked FUS-RNA complex dynamics and stress granule formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11485-E11494}, doi = {10.1073/pnas.1811997115}, pmid = {30442662}, issn = {1091-6490}, support = {R01 NS074324/NS/NINDS NIH HHS/United States ; R01 NS089616/NS/NINDS NIH HHS/United States ; T32 CA009110/CA/NCI NIH HHS/United States ; }, abstract = {The ubiquitin-like protein ubiquilin 2 (UBQLN2) has been genetically and pathologically linked to the neurodegenerative diseases amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), but its normal cellular functions are not well understood. In a search for UBQLN2-interacting proteins, we found an enrichment of stress granule (SG) components, including ALS/FTD-linked heterogeneous ribonucleoprotein fused in sarcoma (FUS). Through the use of an optimized SG detection method, we observed UBQLN2 and its interactors at SGs. A low complexity, Sti1-like repeat region in UBQLN2 was sufficient for its localization to SGs. Functionally, UBQLN2 negatively regulated SG formation. UBQLN2 increased the dynamics of FUS-RNA interaction and promoted the fluidity of FUS-RNA complexes at a single-molecule level. This solubilizing effect corresponded to a dispersal of FUS liquid droplets in vitro and a suppression of FUS SG formation in cells. ALS-linked mutations in UBQLN2 reduced its association with FUS and impaired its function in regulating FUS-RNA complex dynamics and SG formation. These results reveal a previously unrecognized role for UBQLN2 in regulating the early stages of liquid-liquid phase separation by directly modulating the fluidity of protein-RNA complexes and the dynamics of SG formation.}, } @article {pmid30442661, year = {2018}, author = {Tsolakos, N and Durrant, TN and Chessa, T and Suire, SM and Oxley, D and Kulkarni, S and Downward, J and Perisic, O and Williams, RL and Stephens, L and Hawkins, PT}, title = {Quantitation of class IA PI3Ks in mice reveals p110-free-p85s and isoform-selective subunit associations and recruitment to receptors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12176-12181}, pmid = {30442661}, issn = {1091-6490}, support = {MR/R000409/1//Medical Research Council/United Kingdom ; BB/J004456/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; WT085889MA//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; MC_U105184308//Medical Research Council/United Kingdom ; }, abstract = {Class IA PI3Ks have many roles in health and disease. The rules that govern intersubunit and receptor associations, however, remain unclear. We engineered mouse lines in which individual endogenous class IA PI3K subunits were C-terminally tagged with 17aa that could be biotinylated in vivo. Using these tools we quantified PI3K subunits in streptavidin or PDGFR pull-downs and cell lysates. This revealed that p85α and β bound equivalently to p110α or p110β but p85α bound preferentially to p110δ. p85s were found in molar-excess over p110s in a number of contexts including MEFs (p85β, 20%) and liver (p85α, 30%). In serum-starved MEFs, p110-free-p85s were preferentially, compared with heterodimeric p85s, bound to PDGFRs, consistent with in vitro assays that demonstrated they bound PDGFR-based tyrosine-phosphorylated peptides with higher affinity and co-operativity; suggesting they may act to tune a PI3K activation threshold. p110α-heterodimers were recruited 5-6× more efficiently than p110β-heterodimers to activated PDGFRs in MEFs or to PDGFR-based tyrosine-phosphorylated peptides in MEF-lysates. This suggests that PI3Kα has a higher affinity for relevant tyrosine-phosphorylated motifs than PI3Kβ. Nevertheless, PI3Kβ contributes substantially to acute PDGF-stimulation of PIP3 and PKB in MEFs because it is synergistically, and possibly sequentially, activated by receptor-recruitment and small GTPases (Rac/CDC42) via its RBD, whereas parallel activation of PI3Kα is independent of its RBD. These results begin to provide molecular clarity to the rules of engagement between class IA PI3K subunits in vivo and past work describing "excess p85," p85α as a tumor suppressor, and differential receptor activation of PI3Kα and PI3Kβ.}, } @article {pmid30442660, year = {2018}, author = {Berthonneau, J and Obliger, A and Valdenaire, PL and Grauby, O and Ferry, D and Chaudanson, D and Levitz, P and Kim, JJ and Ulm, FJ and Pellenq, RJ}, title = {Mesoscale structure, mechanics, and transport properties of source rocks' organic pore networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12365-12370}, doi = {10.1073/pnas.1808402115}, pmid = {30442660}, issn = {1091-6490}, abstract = {Organic matter is responsible for the generation of hydrocarbons during the thermal maturation of source rock formation. This geochemical process engenders a network of organic hosted pores that governs the flow of hydrocarbons from the organic matter to fractures created during the stimulation of production wells. Therefore, it can be reasonably assumed that predictions of potentially recoverable confined hydrocarbons depend on the geometry of this pore network. Here, we analyze mesoscale structures of three organic porous networks at different thermal maturities. We use electron tomography with subnanometric resolution to characterize their morphology and topology. Our 3D reconstructions confirm the formation of nanopores and reveal increasingly tortuous and connected pore networks in the process of thermal maturation. We then turn the binarized reconstructions into lattice models including information from atomistic simulations to derive mechanical and confined fluid transport properties. Specifically, we highlight the influence of adsorbed fluids on the elastic response. The resulting elastic energy concentrations are localized at the vicinity of macropores at low maturity whereas these concentrations present more homogeneous distributions at higher thermal maturities, due to pores' topology. The lattice models finally allow us to capture the effect of sorption on diffusion mechanisms with a sole input of network geometry. Eventually, we corroborate the dominant impact of diffusion occurring within the connected nanopores, which constitute the limiting factor of confined hydrocarbon transport in source rocks.}, } @article {pmid30442659, year = {2018}, author = {Liu, S and Cheloha, RW and Watanabe, T and Gardella, TJ and Gellman, SH}, title = {Receptor selectivity from minimal backbone modification of a polypeptide agonist.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12383-12388}, doi = {10.1073/pnas.1815294115}, pmid = {30442659}, issn = {1091-6490}, support = {R01 GM056414/GM/NIGMS NIH HHS/United States ; P30 AR066261/AR/NIAMS NIH HHS/United States ; T32 GM008349/GM/NIGMS NIH HHS/United States ; }, abstract = {Human parathyroid hormone (PTH) and N-terminal fragments thereof activate two receptors, hPTHR1 and hPTHR2, which share ∼51% sequence similarity. A peptide comprising the first 34 residues of PTH is fully active at both receptors and is used to treat osteoporosis. We have used this system to explore the hypothesis that backbone modification of a promiscuous peptidic agonist can provide novel receptor-selective agonists. We tested this hypothesis by preparing a set of variants of PTH(1-34)-NH2 that contained a single β-amino-acid residue replacement at each of the first eight positions. These homologs, each containing one additional backbone methylene unit relative to PTH(1-34)-NH2 itself, displayed a wide range of potencies in cell-based assays for PTHR1 or PTHR2 activation. The β-scan series allowed us to identify two homologs, each containing two α→β replacements, that were highly selective, one for PTHR1 and the other for PTHR2. These findings suggest that backbone modification of peptides may provide a general strategy for achieving activation selectivity among polypeptide-modulated receptors, and that success requires consideration of both β2- and β3-residues, which differ in terms of side-chain location.}, } @article {pmid30442534, year = {2019}, author = {Ebner, P and Götz, F}, title = {Bacterial Excretion of Cytoplasmic Proteins (ECP): Occurrence, Mechanism, and Function.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {176-187}, doi = {10.1016/j.tim.2018.10.006}, pmid = {30442534}, issn = {1878-4380}, abstract = {The excretion of cytoplasmic and signal-peptide-less proteins (ECP) by microorganisms and eukaryotes remains a fascinating topic. In principle, it appears to be a waste of energy. However, it turns out that - extracellularly - some cytoplasmic proteins (CPs) exert a completely different function such as contributing to pathogenicity or evasion of the immune system. Such CPs have been referred to as 'moonlighting' proteins. ECP is boosted by many endogenous or external factors that impair the membrane or cell wall structure. There are also differences regarding their mode of release. In some microorganisms they appear to be released directly, while in others they are embedded in membrane vesicles, or bound to the cell envelope. Some CPs might be promising candidates for vaccine developments against major bacterial pathogens.}, } @article {pmid30442527, year = {2019}, author = {McFadden, GI}, title = {Plasmodium: More Don'ts.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {4-6}, doi = {10.1016/j.pt.2018.10.002}, pmid = {30442527}, issn = {1471-5007}, } @article {pmid30442195, year = {2018}, author = {Ngassam, E and Azabji-Kenfack, M and Tankeu, AT and Mfeukeu-Kuate, L and Nganou-Gnindjio, CN and Mba, C and Katte, JC and Dehayem, MY and Mbanya, JC and Sobngwi, E}, title = {Heart rate variability in hyperthyroidism on sub Saharan African patients: a case-control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {814}, pmid = {30442195}, issn = {1756-0500}, abstract = {OBJECTIVE: We aimed to determine heart rate variability in freshly diagnosed untreated hyperthyroidism patients. We enrolled 10 patients (9 females) and 10 matched controls for sex and age. Each eligible patient underwent five different tests according to Ewing battery tests for cardiac autonomic dysfunction assessment. HRV was assessed during each maneuver and on 24 h using a continuous electrocardiogram with automatic estimation of SDNN, RMSSD, LF HF and HF/LH ratio. Results of tests were compared between hyperthyroidism patients and matched controls using the non-parametric test of Mann-Whitney.

RESULTS: Heart rate was significantly higher in patients with thyrotoxicosis (82.91 ± 10.99 vs 67.04 ± 6.80; 0.006) compared to their controls. On time-domain analysis, there was a trend towards reduction in SDNN (39.52 vs. 63.75; p = 0.2) as well as the RMSSD (30.44 vs 64.03; p = 0.09) in patients with hyperthyroidism. The frequency-domain analysis showed non-significant higher values for the LF (43.87 vs 38.85 ± 12.85; p = 0.8) and lower for the HF (32.54 vs 43.39; p = 0.3). Test's results were mostly impaired in hyperthyroid patients and all patients presented abnormal results for parasympathetic activity. Untreated and recently diagnosed hyperthyroidism is associated to an altered parasympathetic activity in sub Saharan African patients.}, } @article {pmid30442192, year = {2018}, author = {Fjellaksel, R and Oteiza, A and Martin-Armas, M and Riss, PJ and Hjelstuen, OK and Kuttner, S and Hansen, JH and Sundset, R}, title = {First in vivo evaluation of a potential SPECT brain radiotracer for the gonadotropin releasing hormone receptor.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {811}, pmid = {30442192}, issn = {1756-0500}, support = {SFP1196-14//Helse Nord RHF/ ; }, abstract = {OBJECTIVES: In vivo evaluations of a gonadotropin releasing hormone-receptor single photon emission computed tomography radiotracer for non-invasive detection of gonadotropin releasing homone-receptors in brain.

RESULTS: We have used a simple, robust and high-yielding procedure to radiolabel an alpha-halogenated bioactive compound with high radiochemical yield. Literature findings showed similar alpha-halogenated compounds suitable for in vivo evaluations. The compound was found to possess nano molar affinity for the gonadotropin releasing hormone-receptor in a competition dependent inhibition study. Furthermore, liquid chromatography-mass spectrometry analysis in saline, human and rat serum resulted in 46%, 52% and 44% stability after incubation for 1 h respectively. In addition, rat brain single photon emission computed tomography and biodistribution studies gave further insight into the nature of the compound as a radiotracer.}, } @article {pmid30442187, year = {2018}, author = {Schell, C and Godinho, A and Kushnir, V and Cunningham, JA}, title = {To send or not to send: weighing the costs and benefits of mailing an advance letter to participants before a telephone survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {813}, pmid = {30442187}, issn = {1756-0500}, support = {704949//Canadian Cancer Society/ ; }, abstract = {OBJECTIVE: A letter was mailed to half the participants (Letter = 137; No Letter = 138) of a 5-year follow-up survey regarding smoking cessation before attempting contact for a telephone interview. The primary outcome was the number of completed surveys per group (response rate). Secondary analyses of the number of telephone calls placed and a cost analysis were performed.

RESULTS: No conclusive effect was found on the response rates per group (59.1% Letter, 50.0% No Letter; p = 0.147). Additionally, a logistic regression, controlling for demographics, revealed that there was no direct effect of sending the letter on response rate (p = 0.369). Non-parametric analysis showed significantly fewer calls (U = 7962.5, z = - 2.274, p < 0.05 two-tailed) and significantly lower costs (U = 11112.00, z = 2.521, p < 0.05 two-tailed) in reaching participants in the Letter group. Mailing an advance letter to participants did not appear to effect response rates between the groups, even when controlling for demographics. However, further analysis examining the number of call attempts and the costs per group revealed the letter may have had other effects. These findings suggest that additional analyses may be merited when evaluating the effectiveness of methods to increase participation, such as an advance letter, especially in cases where the literature largely supports its effectual use. Trial registration ClinicalTrials.gov NCT03097445. Registered 31 March 2017.}, } @article {pmid30442183, year = {2018}, author = {Jackson, C and Barrett, DW and Shumake, J and Gonzales, E and Gonzalez-Lima, F and Lane, MA}, title = {Maternal omega-3 fatty acid intake during neurodevelopment does not affect pup behavior related to depression, novelty, or learning.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {812}, pmid = {30442183}, issn = {1756-0500}, abstract = {OBJECTIVE: Previously, we showed that consumption of a diet supplemented with omega-3 polyunsaturated fatty acids (n-3FAs) for two rounds of gestation and lactation increased the ability of rat dams to cope with stress when compared to dams that ingested a diet lacking n-3FAs. The objective of this study was to determine if the diets of these dams affected the behavior of their pups later in life. To isolate the neurodevelopmental effects of n-3FAs, pups from the second gestation were weaned to a diet adequate in n-3FAs. Pup testing began at 8 weeks of age and consisted of the forced swim, open field, and hole board tests to examine depression-related behavior, reaction to novelty, and learning and memory, respectively.

RESULTS: Given the considerable difference in the n-3FA content of the maternal diet, we expected a large effect size, however with the exception of rearing duration, maternal diet did not affect behavior in any of the tests conducted. These results suggest that maternal n-3FA supplementation during neurodevelopment likely does not affect offspring behavior when a diet adequate in n-3FA is provided post-weaning. Rather, we hypothesize that brain n-3FAs at the time of testing confer altered behavior and corroborate the need for additional research.}, } @article {pmid30442182, year = {2018}, author = {Abdelgader, EA and Eltayeb, NH and Eltahir, TA and Altayeb, OA and Fadul, EA and Abdel Rahman, EM and Merghani, TH}, title = {Evaluation of CD38 expression in Sudanese patients with chronic lymphocytic leukemia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {815}, pmid = {30442182}, issn = {1756-0500}, abstract = {OBJECTIVE: The objective of this study was to evaluate the cluster of differentiation-38 (CD38) expression in Sudanese patients with chronic lymphocytic leukemia (CLL) and to determine its association with clinical and laboratory characteristics of the disease.

RESULTS: We conducted a cross-sectional study on 99 patients diagnosed with CLL in Khartoum Oncology Hospital in Khartoum, Sudan. Immunophenotyping and CD38 expression levels were measured with four-color flowcytometry. The results of physical examination and blood analyses were used for assigning a modified Rai clinical staging system. The collected data were analyzed using the Statistical Package for the Social Science, version 22 (SPSS Inc., Chicago, IL, USA). According to our findings, the frequencies of 7%, 20%, and 30% cutoff levels of CD38 expressions were 68.7%, 41.4%, and 36.4% respectively. CD38 cutoff level of 7% showed a significant association with hemoglobin concentration (P = 0.04), whereas other cutoff levels showed insignificant results. All the three cutoff levels showed insignificant associations with the other clinical and laboratory variables. In conclusion, the CD38 expression at a cutoff level of 7% seems to be more valuable clinically than higher cutoff levels in Sudanese CLL patients.}, } @article {pmid30442124, year = {2018}, author = {Yang, X and Vingron, M}, title = {Classifying human promoters by occupancy patterns identifies recurring sequence elements, combinatorial binding, and spatial interactions.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {138}, pmid = {30442124}, issn = {1741-7007}, abstract = {BACKGROUND: Characterizing recurring sequence patterns in human promoters has been a challenging undertaking even nowadays where a near-complete overview of promoters exists. However, with the more recent availability of genomic location (ChIP-seq) data, one can approach that question through the identification of characteristic patterns of transcription factor occupancy and histone modifications.

RESULTS: Based on the ENCODE annotation and integration of sequence motifs as well as three-dimensional chromatin data, we have undertaken a re-analysis of occupancy and sequence patterns in human promoters. We identify clear groups of CAAT-box and E-box sequence motif containing promoters, as well as a group of promoters whose interaction with an enhancer appears to be mediated by CCCTC-binding factor (CTCF) binding on the promoter. We also extend our analysis to inactive promoters, showing that only a surprisingly small number of inactive promoters is repressed by the polycomb complex. We also identify combinatorial patterns of transcription factor interactions indicated by the ChIP-seq signals.

CONCLUSION: Our analysis defines subgroups of promoters characterized by stereotypic patterns of transcription factor occupancy, and combinations of specific sequence patterns which are required for their binding. This grouping provides new hypotheses concerning the assembly and dynamics of transcription factor complexes at their respective promoter groups, as well as questions on the evolutionary origin of these groups.}, } @article {pmid30442116, year = {2018}, author = {Ryan, BC and Lowe, K and Hanson, L and Gil, T and Braun, L and Howard, PL and Chow, RL}, title = {Mapping the Pax6 3' untranslated region microRNA regulatory landscape.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {820}, pmid = {30442116}, issn = {1471-2164}, abstract = {BACKGROUND: PAX6 is a homeodomain transcription factor that acts in a highly dosage-sensitive manner to regulate the development and function of the eyes, nose, central nervous system, gut, and endocrine pancreas. Several individual microRNAs (miRNA) have been implicated in regulating PAX6 in different cellular contexts, but a more general view of how they contribute to the fine-tuning and homeostasis of PAX6 is poorly understood.

RESULTS: Here, a comprehensive analysis of the Pax6 3' untranslated region was performed to map potential miRNA recognition elements and served as a backdrop for miRNA expression profiling experiments to identify potential cell/tissue-specific miRNA codes. Pax6 3'UTR pull-down studies identified a cohort of miRNA interactors in pancreatic αTC1-6 cells that, based on the spacing of their recognition sites in the Pax6 3'UTR, revealed 3 clusters where cooperative miRNA regulation may occur. Some of these interacting miRNAs have been implicated in α cell function but have not previously been linked to Pax6 function and may therefore represent novel PAX6 regulators.

CONCLUSIONS: These findings reveal a regulatory landscape upon which miRNAs may participate in the developmental control, fine-tuning and/or homeostasis of PAX6 levels.}, } @article {pmid30442113, year = {2018}, author = {McAtee, PA and Brian, L and Curran, B and van der Linden, O and Nieuwenhuizen, NJ and Chen, X and Henry-Kirk, RA and Stroud, EA and Nardozza, S and Jayaraman, J and Rikkerink, EHA and Print, CG and Allan, AC and Templeton, MD}, title = {Re-programming of Pseudomonas syringae pv. actinidiae gene expression during early stages of infection of kiwifruit.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {822}, pmid = {30442113}, issn = {1471-2164}, support = {C11X1205//New Zealand Ministry for Business, Innovation and Employment/ ; N/A//Bioprotection Centre for Research Excellence (NZ)/ ; }, abstract = {BACKGROUND: Pseudomonas syringae is a widespread bacterial species complex that includes a number of significant plant pathogens. Amongst these, P. syringae pv. actinidiae (Psa) initiated a worldwide pandemic in 2008 on cultivars of Actinidia chinensis var. chinensis. To gain information about the expression of genes involved in pathogenicity we have carried out transcriptome analysis of Psa during the early stages of kiwifruit infection.

RESULTS: Gene expression in Psa was investigated during the first five days after infection of kiwifruit plantlets, using RNA-seq. Principal component and heatmap analyses showed distinct phases of gene expression during the time course of infection. The first phase was an immediate transient peak of induction around three hours post inoculation (HPI) that included genes that code for a Type VI Secretion System and nutrient acquisition (particularly phosphate). This was followed by a significant commitment, between 3 and 24 HPI, to the induction of genes encoding the Type III Secretion System (T3SS) and Type III Secreted Effectors (T3SE). Expression of these genes collectively accounted for 6.3% of the bacterial transcriptome at this stage. There was considerable variation in the expression levels of individual T3SEs but all followed the same temporal expression pattern, with the exception of hopAS1, which peaked later in expression at 48 HPI. As infection progressed over the time course of five days, there was an increase in the expression of genes with roles in sugar, amino acid and sulfur transport and the production of alginate and colanic acid. These are both polymers that are major constituents of extracellular polysaccharide substances (EPS) and are involved in biofilm production. Reverse transcription-quantitative PCR (RT-qPCR) on an independent infection time course experiment showed that the expression profile of selected bacterial genes at each infection phase correlated well with the RNA-seq data.

CONCLUSIONS: The results from this study indicate that there is a complex remodeling of the transcriptome during the early stages of infection, with at least three distinct phases of coordinated gene expression. These include genes induced during the immediate contact with the host, those involved in the initiation of infection, and finally those responsible for nutrient acquisition.}, } @article {pmid30442111, year = {2018}, author = {Zhang, X and Lai, Y and Zhang, W and Ahmad, J and Qiu, Y and Zhang, X and Duan, M and Liu, T and Song, J and Wang, H and Li, X}, title = {MicroRNAs and their targets in cucumber shoot apices in response to temperature and photoperiod.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {819}, pmid = {30442111}, issn = {1471-2164}, support = {2016YFD0100204//National Key Research and Development Program of China/ ; CAAS-ASTIP-IVFCAAS//Science and Technology Innovation Program of the Chinese Academy of Agricultural Sciences/ ; 31171961//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: The cucumber is one of the most important vegetables worldwide and is used as a research model for study of phloem transport, sex determination and temperature-photoperiod physiology. The shoot apex is the most important plant tissue in which the cell fate and organ meristems have been determined. In this study, a series of whole-genome small RNA, degradome and transcriptome analyses were performed on cucumber shoot apical tissues treated with high vs. low temperature and long vs. short photoperiod.

RESULTS: A total of 164 known miRNAs derived from 68 families and 203 novel miRNAs from 182 families were identified. Their 4611 targets were predicted using psRobot and TargetFinder, amongst which 349 were validated by degradome sequencing. Fourteen targets of six miRNAs were differentially expressed between the treatments. A total of eight known and 16 novel miRNAs were affected by temperature and photoperiod. Functional annotations revealed that "Plant hormone signal transduction" pathway was significantly over-represented in the miRNA targets. The miR156/157/SBP-Boxes and novel-mir153/ethylene-responsive transcription factor/senescence-related protein/aminotransferase/acyl-CoA thioesterase are the two most credible miRNA/targets combinations modulating the plant's responsive processes to the temperature-photoperiod changes. Moreover, the newly evolved, cucumber-specific novel miRNA (novel-mir153) was found to target 2087 mRNAs by prediction and has 232 targets proven by degradome analysis, accounting for 45.26-58.88% of the total miRNA targets in this plant. This is the largest sum of genes targeted by a single miRNA to the best of our knowledge.

CONCLUSIONS: These results contribute to a better understanding of the miRNAs mediating plant adaptation to combinations of temperature and photoperiod and sheds light on the recent evolution of new miRNAs in cucumber.}, } @article {pmid30442098, year = {2018}, author = {Thomas-Bulle, C and Piednoël, M and Donnart, T and Filée, J and Jollivet, D and Bonnivard, É}, title = {Mollusc genomes reveal variability in patterns of LTR-retrotransposons dynamics.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {821}, pmid = {30442098}, issn = {1471-2164}, abstract = {BACKGROUND: The three superfamilies of Long Terminal Repeat (LTR) retrotransposons are a widespread kind of transposable element and a major factor in eukaryotic genome evolution. In metazoans, recent studies suggested that Copia LTR-retrotransposons display specific dynamic compared to the more abundant and diverse Gypsy elements. Indeed, Copia elements show a relative scarcity and the prevalence of only a few clades in specific hosts. Thus, BEL/Pao seems to be the second most abundant superfamily. However, the generality of these assumptions remains to be assessed. Therefore, we carried out the first large-scale comparative genomic analysis of LTR-retrotransposons in molluscs. The aim of this study was to analyse the diversity, copy numbers, genomic proportions and distribution of LTR-retrotransposons in a large host phylum.

RESULTS: We compare nine genomes of molluscs and further added LTR-retrotransposons sequences detected in databases for 47 additional species. We identified 1709 families, which enabled us to define 31 clades. We show that clade richness was highly dependent on the considered superfamily. We found only three Copia clades, including GalEa and Hydra which appear to be widely distributed and highly dominant as they account for 96% of the characterised Copia elements. Among the seven BEL/Pao clades identified, Sparrow and Surcouf are characterised for the first time. We find no BEL or Pao elements, but the rare clades Dan and Flow are present in molluscs. Finally, we characterised 21 Gypsy clades, only five of which had been previously described, the C-clade being the most abundant one. Even if they are found in the same number of host species, Copia elements are clearly less abundant than BEL/Pao elements in copy number or genomic proportions, while Gypsy elements are always the most abundant ones whatever the parameter considered.

CONCLUSIONS: Our analysis confirms the contrasting dynamics of Copia and Gypsy elements in metazoans and indicates that BEL/Pao represents the second most abundant superfamily, probably reflecting an intermediate dynamic. Altogether, the data obtained in several taxa highly suggest that these patterns can be generalised for most metazoans. Finally, we highlight the importance of using database information in complement of genome analyses when analyzing transposable element diversity.}, } @article {pmid30442092, year = {2018}, author = {Cross, I and Portela-Bens, S and García-Angulo, A and Merlo, MA and Rodríguez, ME and Liehr, T and Rebordinos, L}, title = {A preliminary integrated genetic map distinguishes every chromosome pair and locates essential genes related to abiotic adaptation of Crassostrea angulata/gigas.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {104}, pmid = {30442092}, issn = {1471-2156}, support = {SOE 2/ P1/E287//INTERREG IVB SUDOE/ ; BIO-219//Agencia de Innovación y Desarrollo de Andalucía/ ; }, abstract = {BACKGROUND: The re-sequencing of C. angulata has revealed many polymorphisms in candidate genes related to adaptation to abiotic stress that are not present in C. gigas; these genes, therefore, are probably related to the ability of this oyster to retain high concentrations of toxic heavy metals. There is, in addition, an unresolved controversy as to whether or not C. angulata and C. gigas are the same species or subspecies. Both oysters have 20 metacentric chromosomes of similar size that are morphologically indistinguishable. From a genomic perspective, as a result of the great variation and selection for heterozygotes in C. gigas, the assembly of its draft genome was difficult: it is fragmented in more than seven thousand scaffolds.

RESULTS: In this work sixty BAC sequences of C. gigas downloaded from NCBI were assembled in BAC-contigs and assigned to BACs that were used as probes for mFISH in C. angulata and C. gigas. In addition, probes of H3, H4 histone, 18S and 5S rDNA genes were also used. Hence we obtained markers identifying 8 out the 10 chromosomes constituting the karyotype. Chromosomes 1 and 9 can be distinguished morphologically. The bioinformatic analysis carried out with the BAC-contigs annotated 88 genes. As a result, genes associated with abiotic adaptation, such as metallothioneins, have been positioned in the genome. The gene ontology analysis has also shown many molecular functions related to metal ion binding, a phenomenon associated with detoxification processes that are characteristic in oysters. Hence the provisional integrated map obtained in this study is a useful complementary tool for the study of oyster genomes.

CONCLUSIONS: In this study 8 out of 10 chromosome pairs of Crassostrea angulata/gigas were identified using BAC clones as probes. As a result all chromosomes can now be distinguished. Moreover, FISH showed that H3 and H4 co-localized in two pairs of chromosomes different that those previously escribed. 88 genes were annotated in the BAC-contigs most of them related with Molecular Functions of protein binding, related to the resistance of the species to abiotic stress. An integrated genetic map anchored to the genome has been obtained in which the BAC-contigs structure were not concordant with the gene structure of the C. gigas scaffolds displayed in the Genomicus database.}, } @article {pmid30442091, year = {2018}, author = {Redmond, AK and Macqueen, DJ and Dooley, H}, title = {Phylotranscriptomics suggests the jawed vertebrate ancestor could generate diverse helper and regulatory T cell subsets.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {169}, pmid = {30442091}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Biological Evolution ; Female ; Fishes/genetics ; Genome ; Jaw/*anatomy & histology ; Lymphocyte Subsets/*metabolism ; *Phylogeny ; Sharks/genetics ; T-Lymphocytes, Regulatory/*metabolism ; Transcription Factors/chemistry/metabolism ; Transcriptome/*genetics ; Vertebrates/*genetics ; }, abstract = {BACKGROUND: The cartilaginous fishes diverged from other jawed vertebrates ~ 450 million years ago (mya). Despite this key evolutionary position, the only high-quality cartilaginous fish genome available is for the elephant shark (Callorhinchus milii), a chimaera whose ancestors split from the elasmobranch lineage ~ 420 mya. Initial analysis of this resource led to proposals that key components of the cartilaginous fish adaptive immune system, most notably their array of T cell subsets, was primitive compared to mammals. This proposal is at odds with the robust, antigen-specific antibody responses reported in elasmobranchs following immunization. To explore this discrepancy, we generated a multi-tissue transcriptome for small-spotted catshark (Scyliorhinus canicula), a tractable elasmobranch model for functional studies. We searched this, and other newly available sequence datasets, for CD4+ T cell subset-defining genes, aiming to confirm the presence or absence of each subset in cartilaginous fishes.

RESULTS: We generated a new transcriptome based on a normalised, multi-tissue RNA pool, aiming to maximise representation of tissue-specific and lowly expressed genes. We utilized multiple transcriptomic datasets and assembly variants in phylogenetic reconstructions to unambiguously identify several T cell subset-specific molecules in cartilaginous fishes for the first time, including interleukins, interleukin receptors, and key transcription factors. Our results reveal the inability of standard phylogenetic reconstruction approaches to capture the site-specific evolutionary processes of fast-evolving immune genes but show that site-heterogeneous mixture models can adequately do so.

CONCLUSIONS: Our analyses reveal that cartilaginous fishes are capable of producing a range of CD4+ T cell subsets comparable to that of mammals. Further, that the key molecules required for the differentiation and functioning of these subsets existed in the jawed vertebrate ancestor. Additionally, we highlight the importance of considering phylogenetic diversity and, where possible, utilizing multiple datasets for individual species, to accurately infer gene presence or absence at higher taxonomic levels.}, } @article {pmid30442086, year = {2018}, author = {Abbasi, WA and Asif, A and Ben-Hur, A and Minhas, FUAA}, title = {Learning protein binding affinity using privileged information.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {425}, pmid = {30442086}, issn = {1471-2105}, support = {1564840//Directorate for Biological Sciences/ ; 6085//National Research Program for Universities (NRPU), HEC, Pakistan/ ; }, mesh = {*Algorithms ; Amino Acid Sequence ; Computational Biology/*methods ; Ligands ; *Machine Learning ; Protein Binding ; Proteins/chemistry/*metabolism ; ROC Curve ; Reproducibility of Results ; Support Vector Machine ; }, abstract = {BACKGROUND: Determining protein-protein interactions and their binding affinity are important in understanding cellular biological processes, discovery and design of novel therapeutics, protein engineering, and mutagenesis studies. Due to the time and effort required in wet lab experiments, computational prediction of binding affinity from sequence or structure is an important area of research. Structure-based methods, though more accurate than sequence-based techniques, are limited in their applicability due to limited availability of protein structure data.

RESULTS: In this study, we propose a novel machine learning method for predicting binding affinity that uses protein 3D structure as privileged information at training time while expecting only protein sequence information during testing. Using the method, which is based on the framework of learning using privileged information (LUPI), we have achieved improved performance over corresponding sequence-based binding affinity prediction methods that do not have access to privileged information during training. Our experiments show that with the proposed framework which uses structure only during training, it is possible to achieve classification performance comparable to that which is obtained using structure-based features. Evaluation on an independent test set shows improved performance over the PPA-Pred2 method as well.

CONCLUSIONS: The proposed method outperforms several baseline learners and a state-of-the-art binding affinity predictor not only in cross-validation, but also on an additional validation dataset, demonstrating the utility of the LUPI framework for problems that would benefit from classification using structure-based features. The implementation of LUPI developed for this work is expected to be useful in other areas of bioinformatics as well.}, } @article {pmid30439685, year = {2018}, author = {Banla, LI and Salzman, NH and Kristich, CJ}, title = {Colonization of the mammalian intestinal tract by enterococci.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {26-31}, doi = {10.1016/j.mib.2018.10.005}, pmid = {30439685}, issn = {1879-0364}, support = {R21 AI121552/AI/NIAID NIH HHS/United States ; R21 AI128219/AI/NIAID NIH HHS/United States ; R21 AI132927/AI/NIAID NIH HHS/United States ; R01 GM099526/GM/NIGMS NIH HHS/United States ; R35 GM122503/GM/NIGMS NIH HHS/United States ; }, abstract = {Enterococci are colonizers of the mammalian gastrointestinal tract (GIT) and normally live in healthy association with their human host. However, enterococci are also major causes of healthcare-acquired infections, prompting the US Centers for Disease Control and Prevention to declare vancomycin-resistant enterococci (VRE) a serious threat to public health. Because of both intrinsic and acquired antibiotic resistance, enterococci proliferate in the GIT during antibiotic therapy, leading to dissemination and disease. The recognition that colonization of the GIT is a pre-requisite for enterococcal infections has prompted research to study mechanisms used by enterococci to colonize this niche. This review discusses major findings of recent research to understand GIT colonization by enterococci using diverse experimental models, each of which exhibits unique strengths. This work has revealed enterococcal transcriptional reprogramming in the GIT, contributions of specific enterococcal genes encoded by the core genome to GIT colonization, the impact of genome plasticity, and roles for intra-species and inter-species interactions in modulation of GIT colonization.}, } @article {pmid30439356, year = {2019}, author = {Niimi, Y and Imai, A and Nishimura, H and Yui, K and Kikuchi, A and Koike, H and Saga, Y and Suzuki, A}, title = {Essential role of mouse Dead end1 in the maintenance of spermatogonia.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {103-112}, doi = {10.1016/j.ydbio.2018.11.003}, pmid = {30439356}, issn = {1095-564X}, abstract = {Dead end is a vertebrate-specific RNA-binding protein implicated in germ cell development. We have previously shown that mouse Dead end1 (DND1) is expressed in male embryonic germ cells and directly interacts with NANOS2 to cooperatively promote sexual differentiation of fetal germ cells. In addition, we have also reported that NANOS2 is expressed in self-renewing spermatogonial stem cells and is required for the maintenance of the stem cell state. However, it remains to be determined whether DND1 works with NANOS2 in the spermatogonia. Here, we show that DND1 is expressed in a subpopulation of differentiating spermatogonia and undifferentiated spermatogonia, including NANOS2-positive spermatogonia. Conditional disruption of DND1 depleted both differentiating and undifferentiated spermatogonia; however, the numbers of Asingle and Apaired spermatogonia were preferentially decreased as compared with those of Aaligned spermatogonia. Finally, we found that postnatal DND1 associates with NANOS2 in vivo, independently of RNA, and interacts with some of NANOS2-target mRNAs. These data not only suggest that DND1 is a partner of NANOS2 in undifferentiated spermatogonia as well as in male embryonic germ cells, but also show that DND1 plays an essential role in the survival of differentiating spermatogonia.}, } @article {pmid30431422, year = {2019}, author = {Son, JS and Hwang, YJ and Lee, SY and Ghim, SY}, title = {Bacillus salidurans sp. nov., isolated from salt-accumulated pepper rhizospheric soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {116-122}, doi = {10.1099/ijsem.0.003110}, pmid = {30431422}, issn = {1466-5034}, abstract = {A Gram-stain-positive, facultatively anaerobic, motile and rod-shaped bacterium, designated KNUC7312T, was isolated from salt-accumulated rhizospheric soil in a pepper greenhouse in Miryang city, Republic of Korea. Cell growth of strain KNUC7312T occurred at 10-45 °C (optimum, 30 °C) and pH 7-12 (optimum, pH 7). In addition, this strain was able to tolerate 0-12 % NaCl (w/v) concentration (optimum, 0-1 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain KNUC7312T clustered together with other species of the genus Bacillus and was most closely related to Bacillus humi DSM 16318T (98.0 %). The predominant respiratory quinone was menaquinone-7 (MK-7). The major cellular fatty acids were anteiso C15 : 0, iso-C15 : 0 and iso-C14 : 0. The polar lipid profile contained the major components diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and two unidentified aminolipids. The cell-wall peptidoglycan contained meso-diaminopimelic acid as the major diagnostic diamino acid. Strain KNUC7312T showed a low DNA-DNA relatedness value (47.36 %) with B. humi DSM 16318T, which supported that this strain represents a novel Bacillusspecies. On the basis of phenotypic, chemotaxonomic and phylogenetic evidence, strain KNUC7312T represents a novel species within the genera Bacillus. The name Bacillus salildurans sp. nov. is proposed. The type strain is KNUC7312T (KCTC 33852T=CGMCC 1.13629T).}, } @article {pmid30431420, year = {2019}, author = {Phurbu, D and Pema, Y and Ma, C and Lu, H and Li, H and Tian, Y and Xing, P}, title = {Nitrincola tibetensis sp. nov., isolated from Lake XuguoCo on the Tibetan Plateau.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {123-128}, doi = {10.1099/ijsem.0.003111}, pmid = {30431420}, issn = {1466-5034}, abstract = {A novel Gram-stain-negative, motile and rod-shaped bacterium, designated xg18T, was isolated from Lake XuguoCo on the Tibetan Plateau. The strain was able to grow optimally at 0-2 % NaCl and tolerate up to 6 % NaCl. Growth occurred at pH 7.0-11.0 (optimum, pH 9.0-10.0) and 15-40 °C (optimum, 37 °C). Vitamins were not required for growth. The major polar lipids of strain xg18T were phosphatidyl ethanolamine and phosphatidylglycerol. The predominant respiratory quinone was Q-8. The major fatty acids were summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The G+C content of genomic DNA was 46.1 mol%. Analysis of 16S rRNA sequences showed that strain xg18T belongs to the genus Nitrincola, with Nitrincola alkalisediminis MEB087T (KC822363, 98.6 %) as its closest neighbour. The DNA-DNA relatedness value of strain xg18T with its closest phylogenetic neighbour, N. alkalisediminis JCM 19317T, was 43.1±3.2 %. Strain xg18T was clearly distinguishable from the type strain of the genus Nitrincola through phylogenetic analysis, fatty acid composition data and a range of physiological and biochemical characteristics comparisons. Based on its phenotypic and chemotaxonomic characteristics, strain xg18T could be classified as a representative of a novel species of the genus for which the name Nitrincola tibetensis sp. nov. is proposed. The type strain is xg18T (=CICC 24457T=KCTC 62401T).}, } @article {pmid30431417, year = {2019}, author = {Thanh, VN and Hien, DD}, title = {Moniliella floricola sp. nov., a species of black yeast isolated from flowers.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {87-92}, doi = {10.1099/ijsem.0.003099}, pmid = {30431417}, issn = {1466-5034}, abstract = {Moniliella yeasts were isolated from flower samples collected in Vietnam using an enrichment medium containing 50 % (w/w) glucose. The yeasts were identified as M. byzovii, M. dehoogii, M. megachiliensis, M. mellis, M. nigrescens and M. spathulata. A group of 20 strains representing a hitherto undescribed species of Moniliella was detected. ITS sequences indicated the presence of four genetic variants differing from each other by 4-14 nt. The strains, however, were identical in the TEF1 sequences and shared 1-2 nt differences in the D1/D2 regions. In the ITS-D1/D2 phylogenetic tree, the strains grouped together and formed a well-supported clade with insect-associated Moniliella species, including M. pollinis, M. megachiliensis and M. oedocephalis. The new group was most closely related to M. pollinis but differed from the latter by 95 nt (58 substitutions, 37 indels) in the ITS, 36 nt (31 substitutions, five indels) in the D1/D2, and 30 nt (30 substitutions) in the TEF1 sequences. Moniliella floricola sp. nov. is proposed to accommodate this group of isolates. The type strain and MycoBank number of M. floricola sp. nov. are TBY 30.1T (=CBS 12758T=NRRL Y-63660T) and MB 825274, respectively.}, } @article {pmid30431416, year = {2018}, author = {Perez-Lopez, E and Vincent, C and Moreau, D and Hammond, C and Town, J and Dumonceaux, TJ}, title = {A novel 'Candidatus Phytoplasma asteris' subgroup 16SrI-(E/AI)AI associated with blueberry stunt disease in eastern Canada.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003100}, pmid = {30431416}, issn = {1466-5034}, abstract = {Phytoplasmas ('Candidatus Phytoplasma' species) are phytopathogenic bacteria vectored by insects and are associated with crop diseases that cause severe yield losses by affecting reproductive tissue development. Infection of northern highbush blueberry plants (Vaccinium corymbosum; Ericaceae) with phytoplasma leads to yield losses by altering plant development resulting in stunting and subsequent plant death. Samples collected from symptomatic blueberry plants in two important blueberry-producing areas in Canada, in the provinces of Québec and Nova Scotia, were analysed for the presence of DNA sequences associated with phytoplasma. Analysis of the 16S rRNA gene sequences demonstrated that the plants were infected with a strain of 'Candidatus Phytoplasma asteris', which was previously identified as blueberry stunt phytoplasma (BBS; 16SrI-E). Examination of further bacterial sequences revealed that two distinct 16S rRNA-encoding gene sequences were present in each sample in combination with a single chaperonin-60 (cpn60) sequence and a single rpoperon sequence, suggesting that this strain displays 16S rRNA-encoding gene sequence heterogeneity. Two distinct rrnoperons, rrnE and the newly described rrnAI, were identified in samples analysed from all geographic locations. We propose, based on the sequences obtained, delineating the new subgroup 16SrI-(E/AI)AI, following the nomenclature proposed for heterogeneous subgroups. To our knowledge, this is the first report of a heterogeneous phytoplasma strain affecting blueberry plants and associated with blueberry stunt disease.}, } @article {pmid30431415, year = {2019}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 10 of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {10-12}, doi = {10.1099/ijsem.0.003107}, pmid = {30431415}, issn = {1466-5034}, } @article {pmid30431413, year = {2019}, author = {Shi, YL and Sun, Y and Jiang, ZM and Ruan, ZY and Su, J and Yu, LY and Zhang, YQ}, title = {Simplicispira lacusdiani sp. nov., a novel betaproteobacterium isolated from a freshwater reservoir.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {129-133}, doi = {10.1099/ijsem.0.003112}, pmid = {30431413}, issn = {1466-5034}, abstract = {A Gram-stain-negative, motile, rod-shaped bacterium, designated CPCC 100842T, was isolated from a freshwater reservoir in south-west China. The 16S rRNA gene sequence comparison of strain CPCC 100842T with the available sequences in the GenBank database showed that the isolate was closely related to members of the family Comamonadaceae, with the highest similarities to Simplicispira metamorpha DSM 1837T (98.05 %), Simplicispira limi KCTC 12608T (97.86 %), Simplicispira psychrophila LMG 5408T (97.04 %) and Simplicispira piscis JCM 19291T (97.0 %). In the phylogenetic tree based on 16S rRNA gene sequences, strain CPCC 100842T formed a distinct phylogenetic subclade within the genus Simplicispira. The major cellular fatty acids were as C16 : 0 and summed feature 3 (C16 : 1 ω7c/C16 : 1ω6c). Q-8 was detected as the only respiratory quinone. Phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, aminophospholipid and glycolipid were found in the polar lipid extraction. The genomic DNA G+C content was 67.4 mol%. The average nucleotide identity value was 80.4 % by comparing the draft genome sequences of strain CPCC 100842T and S. metamorpha DSM 1837T. The DNA-DNA hybridization result between strain CPCC 100842T and S. metamorpha DSM 1837T showed 37±3 % genomic relatedness. On the basis of the genotypic analysis and phenotypic characteristics, we propose that strain CPCC 100842T represents a novel species of the genus Simplicispira in the family Comamonadaceae with the name Simplicispira lacusdiani sp. nov. Strain CPCC 100842T (=KCTC 52093T=DSM 102231T) is the type strain of the species.}, } @article {pmid30431239, year = {2019}, author = {Berry, D}, title = {Up-close-and-personal with the human microbiome.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {17-19}, doi = {10.1111/1758-2229.12709}, pmid = {30431239}, issn = {1758-2229}, } @article {pmid30431224, year = {2019}, author = {Koskella, B}, title = {New approaches to characterizing bacteria-phage interactions in microbial communities and microbiomes.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {15-16}, doi = {10.1111/1758-2229.12706}, pmid = {30431224}, issn = {1758-2229}, } @article {pmid30430551, year = {2019}, author = {Wahl, LM and Betti, MI and Dick, DW and Pattenden, T and Puccini, AJ}, title = {Evolutionary stability of the lysis-lysogeny decision: Why be virulent?.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {92-98}, doi = {10.1111/evo.13648}, pmid = {30430551}, issn = {1558-5646}, support = {RPGIN 238389//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Lytic viruses infect and kill host cells, producing a large number of viral copies. Temperate viruses, in contrast, are able to integrate viral genetic material into the host cell DNA, leaving a viable host cell. The evolutionary advantage of this strategy, lysogeny, has been demonstrated in complex environments that include spatial structure, oscillating population dynamics, or periodic environmental collapse. Here, we examine the evolutionary stability of the lysis-lysogeny decision, that is, we predict the long-term outcome of the evolution of lysogeny rates. We demonstrate that viruses with high rates of lysogeny are stable against invasion by more virulent viral strains even in simple environments, as long as the pool of susceptible hosts is not unlimited. This mirrors well-known results in both r-K selection theory and virulence evolution: although virulent viruses have a faster potential growth rate, temperate strains are able to maintain positive growth on a lower density of the limiting resource, susceptible hosts. We then outline scenarios in which the rate of lysogeny is predicted to evolve either toward full lysogeny or full lysis. Finally, we demonstrate conditions under which intermediate rates of lysogeny, as observed in temperate viruses in nature, can be sustained long-term. In general, intermediate lysogeny rates persist when the coupling between susceptible host density and virus density is relaxed.}, } @article {pmid30430240, year = {2018}, author = {Fujimoto, K and Hasebe, T and Kajita, M and Ishizuya-Oka, A}, title = {Expression of hyaluronan synthases upregulated by thyroid hormone is involved in intestinal stem cell development during Xenopus laevis metamorphosis.}, journal = {Development genes and evolution}, volume = {228}, number = {6}, pages = {267-273}, pmid = {30430240}, issn = {1432-041X}, support = {JP17K07475//JSPS KAKENHI Grant/ ; JP18K06320//JSPS KAKENHI Grant/ ; }, abstract = {During amphibian intestinal remodeling, thyroid hormone (TH) induces adult stem cells, which newly generate the absorptive epithelium analogous to the mammalian one. We have previously shown that hyaluronan (HA) is newly synthesized and plays an essential role in the development of the stem cells via its major receptor CD44 in the Xenopus laevis intestine. We here focused on HA synthase (HAS) and examined how the expression of HAS family genes is regulated during natural and TH-induced metamorphosis. Our quantitative RT-PCR analysis indicated that the mRNA expression of HAS2 and HAS3, but not that of HAS1 and HAS-rs, a unique Xenopus HAS-related sequence, is upregulated concomitantly with the development of adult epithelial primordia consisting of the stem/progenitor cells during the metamorphic climax. In addition, our in situ hybridization analysis indicated that the HAS3 mRNA is specifically expressed in the adult epithelial primordia, whereas HAS2 mRNA is expressed in both the adult epithelial primordia and nearby connective tissue cells during this period. Furthermore, by treating X. laevis tadpoles with 4-methylumbelliferone, a HA synthesis inhibitor, we have experimentally shown that inhibition of HA synthesis leads to suppression of TH-upregulated expression of leucine-rich repeat-containing G protein-coupled 5 (LGR5), an intestinal stem cell marker, CD44, HAS2, HAS3, and gelatinase A in vivo. These findings suggest that HA newly synthesized by HAS2 and/or HAS3 is required for intestinal stem cell development through a positive feedback loop and is involved in the formation of the stem cell niche during metamorphosis.}, } @article {pmid30430010, year = {2018}, author = {Klein, LD and Huang, J and Quinn, EA and Martin, MA and Breakey, AA and Gurven, M and Kaplan, H and Valeggia, C and Jasienska, G and Scelza, B and Lebrilla, CB and Hinde, K}, title = {Variation among populations in the immune protein composition of mother's milk reflects subsistence pattern.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {230-245}, pmid = {30430010}, issn = {2050-6201}, abstract = {Lay Summary: Adaptive immune proteins in mothers' milk are more variable than innate immune proteins across populations and subsistence strategies. These results suggest that the immune defenses in milk are shaped by a mother's environment throughout her life.

Background and objectives: Mother's milk contains immune proteins that play critical roles in protecting the infant from infection and priming the infant's developing immune system during early life. The composition of these molecules in milk, particularly the acquired immune proteins, is thought to reflect a mother's immunological exposures throughout her life. In this study, we examine the composition of innate and acquired immune proteins in milk across seven populations with diverse disease and cultural ecologies.

Methodology: Milk samples (n = 164) were collected in Argentina, Bolivia, Nepal, Namibia, Philippines, Poland and the USA. Populations were classified as having one of four subsistence patterns: urban-industrialism, rural-shop, horticulturalist-forager or agro-pastoralism. Milk innate (lactalbumin, lactoferrin and lysozyme) and acquired (Secretory IgA, IgG and IgM) protein concentrations were determined using triple-quadrupole mass spectrometry.

Results: Both innate and acquired immune protein composition in milk varied among populations, though the acquired immune protein composition of milk differed more among populations. Populations living in closer geographic proximity or having similar subsistence strategies (e.g. agro-pastoralists from Nepal and Namibia) had more similar milk immune protein compositions. Agro-pastoralists had different milk innate immune protein composition from horticulturalist-foragers and urban-industrialists. Acquired immune protein composition differed among all subsistence strategies except horticulturist-foragers and rural-shop.

Conclusions and implications: Our results reveal fundamental variation in milk composition that has not been previously explored in human milk research. Further study is needed to understand what specific aspects of the local environment influence milk composition and the effects this variation may have on infant health outcomes.}, } @article {pmid30429615, year = {2018}, author = {Matthews, BJ and Dudchenko, O and Kingan, SB and Koren, S and Antoshechkin, I and Crawford, JE and Glassford, WJ and Herre, M and Redmond, SN and Rose, NH and Weedall, GD and Wu, Y and Batra, SS and Brito-Sierra, CA and Buckingham, SD and Campbell, CL and Chan, S and Cox, E and Evans, BR and Fansiri, T and Filipović, I and Fontaine, A and Gloria-Soria, A and Hall, R and Joardar, VS and Jones, AK and Kay, RGG and Kodali, VK and Lee, J and Lycett, GJ and Mitchell, SN and Muehling, J and Murphy, MR and Omer, AD and Partridge, FA and Peluso, P and Aiden, AP and Ramasamy, V and Rašić, G and Roy, S and Saavedra-Rodriguez, K and Sharan, S and Sharma, A and Smith, ML and Turner, J and Weakley, AM and Zhao, Z and Akbari, OS and Black, WC and Cao, H and Darby, AC and Hill, CA and Johnston, JS and Murphy, TD and Raikhel, AS and Sattelle, DB and Sharakhov, IV and White, BJ and Zhao, L and Aiden, EL and Mann, RS and Lambrechts, L and Powell, JR and Sharakhova, MV and Tu, Z and Robertson, HM and McBride, CS and Hastie, AR and Korlach, J and Neafsey, DE and Phillippy, AM and Vosshall, LB}, title = {Improved reference genome of Aedes aegypti informs arbovirus vector control.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {501-507}, doi = {10.1038/s41586-018-0692-z}, pmid = {30429615}, issn = {1476-4687}, support = {U01 HL130010/HL/NHLBI NIH HHS/United States ; UL1 TR000043/TR/NCATS NIH HHS/United States ; R35 GM118336/GM/NIGMS NIH HHS/United States ; K22 AI113060/AI/NIAID NIH HHS/United States ; UM1 HG009375/HG/NHGRI NIH HHS/United States ; R01 DC014247/DC/NIDCD NIH HHS/United States ; R01 AI101112/AI/NIAID NIH HHS/United States ; R01 AI123338/AI/NIAID NIH HHS/United States ; DP2 OD008540/OD/NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; R21 AI121853/AI/NIAID NIH HHS/United States ; R21 AI123937/AI/NIAID NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; }, abstract = {Female Aedes aegypti mosquitoes infect more than 400 million people each year with dangerous viral pathogens including dengue, yellow fever, Zika and chikungunya. Progress in understanding the biology of mosquitoes and developing the tools to fight them has been slowed by the lack of a high-quality genome assembly. Here we combine diverse technologies to produce the markedly improved, fully re-annotated AaegL5 genome assembly, and demonstrate how it accelerates mosquito science. We anchored physical and cytogenetic maps, doubled the number of known chemosensory ionotropic receptors that guide mosquitoes to human hosts and egg-laying sites, provided further insight into the size and composition of the sex-determining M locus, and revealed copy-number variation among glutathione S-transferase genes that are important for insecticide resistance. Using high-resolution quantitative trait locus and population genomic analyses, we mapped new candidates for dengue vector competence and insecticide resistance. AaegL5 will catalyse new biological insights and intervention strategies to fight this deadly disease vector.}, } @article {pmid30429614, year = {2018}, author = {Liang, Q and Monetti, C and Shutova, MV and Neely, EJ and Hacibekiroglu, S and Yang, H and Kim, C and Zhang, P and Li, C and Nagy, K and Mileikovsky, M and Gyongy, I and Sung, HK and Nagy, A}, title = {Linking a cell-division gene and a suicide gene to define and improve cell therapy safety.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {701-704}, doi = {10.1038/s41586-018-0733-7}, pmid = {30429614}, issn = {1476-4687}, abstract = {Human pluripotent cell lines hold enormous promise for the development of cell-based therapies. Safety, however, is a crucial prerequisite condition for clinical applications. Numerous groups have attempted to eliminate potentially harmful cells through the use of suicide genes1, but none has quantitatively defined the safety level of transplant therapies. Here, using genome-engineering strategies, we demonstrate the protection of a suicide system from inactivation in dividing cells. We created a transcriptional link between the suicide gene herpes simplex virus thymidine kinase (HSV-TK) and a cell-division gene (CDK1); this combination is designated the safe-cell system. Furthermore, we used a mathematical model to quantify the safety level of the cell therapy as a function of the number of cells that is needed for the therapy and the type of genome editing that is performed. Even with the highly conservative estimates described here, we anticipate that our solution will rapidly accelerate the entry of cell-based medicine into the clinic.}, } @article {pmid30429613, year = {2018}, author = {Fadrique, B and Báez, S and Duque, Á and Malizia, A and Blundo, C and Carilla, J and Osinaga-Acosta, O and Malizia, L and Silman, M and Farfán-Ríos, W and Malhi, Y and Young, KR and Cuesta C, F and Homeier, J and Peralvo, M and Pinto, E and Jadan, O and Aguirre, N and Aguirre, Z and Feeley, KJ}, title = {Widespread but heterogeneous responses of Andean forests to climate change.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {207-212}, doi = {10.1038/s41586-018-0715-9}, pmid = {30429613}, issn = {1476-4687}, support = {DEB-1350125//US National Science Foundation/International ; DEB-1754647//US National Science Foundation/International ; DEB-1258112//US National Science Foundation/International ; EAR-1338694//US National Science Foundation/International ; }, abstract = {Global warming is forcing many species to shift their distributions upward, causing consequent changes in the compositions of species that occur at specific locations. This prediction remains largely untested for tropical trees. Here we show, using a database of nearly 200 Andean forest plot inventories spread across more than 33.5° latitude (from 26.8° S to 7.1° N) and 3,000-m elevation (from 360 to 3,360 m above sea level), that tropical and subtropical tree communities are experiencing directional shifts in composition towards having greater relative abundances of species from lower, warmer elevations. Although this phenomenon of 'thermophilization' is widespread throughout the Andes, the rates of compositional change are not uniform across elevations. The observed heterogeneity in thermophilization rates is probably because of different warming rates and/or the presence of specialized tree communities at ecotones (that is, at the transitions between distinct habitats, such as at the timberline or at the base of the cloud forest). Understanding the factors that determine the directions and rates of compositional changes will enable us to better predict, and potentially mitigate, the effects of climate change on tropical forests.}, } @article {pmid30429612, year = {2018}, author = {Sawangjit, A and Oyanedel, CN and Niethard, N and Salazar, C and Born, J and Inostroza, M}, title = {The hippocampus is crucial for forming non-hippocampal long-term memory during sleep.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {109-113}, doi = {10.1038/s41586-018-0716-8}, pmid = {30429612}, issn = {1476-4687}, abstract = {There is a long-standing division in memory research between hippocampus-dependent memory and non-hippocampus-dependent memory, as only the latter can be acquired and retrieved in the absence of normal hippocampal function1,2. Consolidation of hippocampus-dependent memory, in particular, is strongly supported by sleep3-5. Here we show that the formation of long-term representations in a rat model of non-hippocampus-dependent memory depends not only on sleep but also on activation of a hippocampus-dependent mechanism during sleep. Rats encoded non-hippocampus-dependent (novel-object recognition6-8) and hippocampus-dependent (object-place recognition) memories before a two-hour period of sleep or wakefulness. Memory was tested either immediately thereafter or remotely (after one or three weeks). Whereas object-place recognition memory was stronger for rats that had slept after encoding (rather than being awake) at both immediate and remote testing, novel-object recognition memory profited from sleep only three weeks after encoding, at which point it was preserved in rats that had slept after encoding but not in those that had been awake. Notably, inactivation of the hippocampus during post-encoding sleep by intrahippocampal injection of muscimol abolished the sleep-induced enhancement of remote novel-object recognition memory. By contrast, muscimol injection before remote retrieval or memory encoding had no effect on test performance, confirming that the encoding and retrieval of novel-object recognition memory are hippocampus-independent. Remote novel-object recognition memory was associated with spindle activity during post-encoding slow-wave sleep, consistent with the view that neuronal memory replay during slow-wave sleep contributes to long-term memory formation. Our results indicate that the hippocampus has an important role in long-term consolidation during sleep even for memories that have previously been considered hippocampus-independent.}, } @article {pmid30429611, year = {2018}, author = {Lax, G and Eglit, Y and Eme, L and Bertrand, EM and Roger, AJ and Simpson, AGB}, title = {Hemimastigophora is a novel supra-kingdom-level lineage of eukaryotes.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {410-414}, doi = {10.1038/s41586-018-0708-8}, pmid = {30429611}, issn = {1476-4687}, abstract = {Almost all eukaryote life forms have now been placed within one of five to eight supra-kingdom-level groups using molecular phylogenetics1-4. The 'phylum' Hemimastigophora is probably the most distinctive morphologically defined lineage that still awaits such a phylogenetic assignment. First observed in the nineteenth century, hemimastigotes are free-living predatory protists with two rows of flagella and a unique cell architecture5-7; to our knowledge, no molecular sequence data or cultures are currently available for this group. Here we report phylogenomic analyses based on high-coverage, cultivation-independent transcriptomics that place Hemimastigophora outside of all established eukaryote supergroups. They instead comprise an independent supra-kingdom-level lineage that most likely forms a sister clade to the 'Diaphoretickes' half of eukaryote diversity (that is, the 'stramenopiles, alveolates and Rhizaria' supergroup (Sar), Archaeplastida and Cryptista, as well as other major groups). The previous ranking of Hemimastigophora as a phylum understates the evolutionary distinctiveness of this group, which has considerable importance for investigations into the deep-level evolutionary history of eukaryotic life-ranging from understanding the origins of fundamental cell systems to placing the root of the tree. We have also established the first culture of a hemimastigote (Hemimastix kukwesjijk sp. nov.), which will facilitate future genomic and cell-biological investigations into eukaryote evolution and the last eukaryotic common ancestor.}, } @article {pmid30429610, year = {2018}, author = {Lei, Z and Liu, X and Wu, Y and Wang, H and Jiang, S and Wang, S and Hui, X and Wu, Y and Gault, B and Kontis, P and Raabe, D and Gu, L and Zhang, Q and Chen, H and Wang, H and Liu, J and An, K and Zeng, Q and Nieh, TG and Lu, Z}, title = {Enhanced strength and ductility in a high-entropy alloy via ordered oxygen complexes.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {546-550}, doi = {10.1038/s41586-018-0685-y}, pmid = {30429610}, issn = {1476-4687}, abstract = {Oxygen, one of the most abundant elements on Earth, often forms an undesired interstitial impurity or ceramic phase (such as an oxide particle) in metallic materials. Even when it adds strength, oxygen doping renders metals brittle1-3. Here we show that oxygen can take the form of ordered oxygen complexes, a state in between oxide particles and frequently occurring random interstitials. Unlike traditional interstitial strengthening4,5, such ordered interstitial complexes lead to unprecedented enhancement in both strength and ductility in compositionally complex solid solutions, the so-called high-entropy alloys (HEAs)6-10. The tensile strength is enhanced (by 48.5 ± 1.8 per cent) and ductility is substantially improved (by 95.2 ± 8.1 per cent) when doping a model TiZrHfNb HEA with 2.0 atomic per cent oxygen, thus breaking the long-standing strength-ductility trade-off11. The oxygen complexes are ordered nanoscale regions within the HEA characterized by (O, Zr, Ti)-rich atomic complexes whose formation is promoted by the existence of chemical short-range ordering among some of the substitutional matrix elements in the HEAs. Carbon has been reported to improve strength and ductility simultaneously in face-centred cubic HEAs12, by lowering the stacking fault energy and increasing the lattice friction stress. By contrast, the ordered interstitial complexes described here change the dislocation shear mode from planar slip to wavy slip, and promote double cross-slip and thus dislocation multiplication through the formation of Frank-Read sources (a mechanism explaining the generation of multiple dislocations) during deformation. This ordered interstitial complex-mediated strain-hardening mechanism should be particularly useful in Ti-, Zr- and Hf-containing alloys, in which interstitial elements are highly undesirable owing to their embrittlement effects, and in alloys where tuning the stacking fault energy and exploiting athermal transformations13 do not lead to property enhancement. These results provide insight into the role of interstitial solid solutions and associated ordering strengthening mechanisms in metallic materials.}, } @article {pmid30429609, year = {2018}, author = {Houbaert, A and Zhang, C and Tiwari, M and Wang, K and de Marcos Serrano, A and Savatin, DV and Urs, MJ and Zhiponova, MK and Gudesblat, GE and Vanhoutte, I and Eeckhout, D and Boeren, S and Karimi, M and Betti, C and Jacobs, T and Fenoll, C and Mena, M and de Vries, S and De Jaeger, G and Russinova, E}, title = {POLAR-guided signalling complex assembly and localization drive asymmetric cell division.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {574-578}, doi = {10.1038/s41586-018-0714-x}, pmid = {30429609}, issn = {1476-4687}, abstract = {Stomatal cell lineage is an archetypal example of asymmetric cell division (ACD), which is necessary for plant survival1-4. In Arabidopsis thaliana, the GLYCOGEN SYNTHASE KINASE3 (GSK3)/SHAGGY-like kinase BRASSINOSTEROID INSENSITIVE 2 (BIN2) phosphorylates both the mitogen-activated protein kinase (MAPK) signalling module5,6 and its downstream target, the transcription factor SPEECHLESS (SPCH)7, to promote and restrict ACDs, respectively, in the same stomatal lineage cell. However, the mechanisms that balance these mutually exclusive activities remain unclear. Here we identify the plant-specific protein POLAR as a stomatal lineage scaffold for a subset of GSK3-like kinases that confines them to the cytosol and subsequently transiently polarizes them within the cell, together with BREAKING OF ASYMMETRY IN THE STOMATAL LINEAGE (BASL), before ACD. As a result, MAPK signalling is attenuated, enabling SPCH to drive ACD in the nucleus. Moreover, POLAR turnover requires phosphorylation on specific residues, mediated by GSK3. Our study reveals a mechanism by which the scaffolding protein POLAR ensures GSK3 substrate specificity, and could serve as a paradigm for understanding regulation of GSK3 in plants.}, } @article {pmid30429608, year = {2018}, author = {Shen, SY and Singhania, R and Fehringer, G and Chakravarthy, A and Roehrl, MHA and Chadwick, D and Zuzarte, PC and Borgida, A and Wang, TT and Li, T and Kis, O and Zhao, Z and Spreafico, A and Medina, TDS and Wang, Y and Roulois, D and Ettayebi, I and Chen, Z and Chow, S and Murphy, T and Arruda, A and O'Kane, GM and Liu, J and Mansour, M and McPherson, JD and O'Brien, C and Leighl, N and Bedard, PL and Fleshner, N and Liu, G and Minden, MD and Gallinger, S and Goldenberg, A and Pugh, TJ and Hoffman, MM and Bratman, SV and Hung, RJ and De Carvalho, DD}, title = {Sensitive tumour detection and classification using plasma cell-free DNA methylomes.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {579-583}, doi = {10.1038/s41586-018-0703-0}, pmid = {30429608}, issn = {1476-4687}, abstract = {The use of liquid biopsies for cancer detection and management is rapidly gaining prominence1. Current methods for the detection of circulating tumour DNA involve sequencing somatic mutations using cell-free DNA, but the sensitivity of these methods may be low among patients with early-stage cancer given the limited number of recurrent mutations2-5. By contrast, large-scale epigenetic alterations-which are tissue- and cancer-type specific-are not similarly constrained6 and therefore potentially have greater ability to detect and classify cancers in patients with early-stage disease. Here we develop a sensitive, immunoprecipitation-based protocol to analyse the methylome of small quantities of circulating cell-free DNA, and demonstrate the ability to detect large-scale DNA methylation changes that are enriched for tumour-specific patterns. We also demonstrate robust performance in cancer detection and classification across an extensive collection of plasma samples from several tumour types. This work sets the stage to establish biomarkers for the minimally invasive detection, interception and classification of early-stage cancers based on plasma cell-free DNA methylation patterns.}, } @article {pmid30429607, year = {2018}, author = {Poillet-Perez, L and Xie, X and Zhan, L and Yang, Y and Sharp, DW and Hu, ZS and Su, X and Maganti, A and Jiang, C and Lu, W and Zheng, H and Bosenberg, MW and Mehnert, JM and Guo, JY and Lattime, E and Rabinowitz, JD and White, E}, title = {Autophagy maintains tumour growth through circulating arginine.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {569-573}, pmid = {30429607}, issn = {1476-4687}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; R01 CA193970/CA/NCI NIH HHS/United States ; K22 CA190521/CA/NCI NIH HHS/United States ; R01 CA163591/CA/NCI NIH HHS/United States ; S10 OD016400/OD/NIH HHS/United States ; R50 CA211437/CA/NCI NIH HHS/United States ; R01 CA130893/CA/NCI NIH HHS/United States ; R01 CA188096/CA/NCI NIH HHS/United States ; }, abstract = {Autophagy captures intracellular components and delivers them to lysosomes, where they are degraded and recycled to sustain metabolism and to enable survival during starvation1-5. Acute, whole-body deletion of the essential autophagy gene Atg7 in adult mice causes a systemic metabolic defect that manifests as starvation intolerance and gradual loss of white adipose tissue, liver glycogen and muscle mass1. Cancer cells also benefit from autophagy. Deletion of essential autophagy genes impairs the metabolism, proliferation, survival and malignancy of spontaneous tumours in models of autochthonous cancer6,7. Acute, systemic deletion of Atg7 or acute, systemic expression of a dominant-negative ATG4b in mice induces greater regression of KRAS-driven cancers than does tumour-specific autophagy deletion, which suggests that host autophagy promotes tumour growth1,8. Here we show that host-specific deletion of Atg7 impairs the growth of multiple allografted tumours, although not all tumour lines were sensitive to host autophagy status. Loss of autophagy in the host was associated with a reduction in circulating arginine, and the sensitive tumour cell lines were arginine auxotrophs owing to the lack of expression of the enzyme argininosuccinate synthase 1. Serum proteomic analysis identified the arginine-degrading enzyme arginase I (ARG1) in the circulation of Atg7-deficient hosts, and in vivo arginine metabolic tracing demonstrated that serum arginine was degraded to ornithine. ARG1 is predominantly expressed in the liver and can be released from hepatocytes into the circulation. Liver-specific deletion of Atg7 produced circulating ARG1, and reduced both serum arginine and tumour growth. Deletion of Atg5 in the host similarly regulated [corrected] circulating arginine and suppressed tumorigenesis, which demonstrates that this phenotype is specific to autophagy function rather than to deletion of Atg7. Dietary supplementation of Atg7-deficient hosts with arginine partially restored levels of circulating arginine and tumour growth. Thus, defective autophagy in the host leads to the release of ARG1 from the liver and the degradation of circulating arginine, which is essential for tumour growth; this identifies a metabolic vulnerability of cancer.}, } @article {pmid30429606, year = {2018}, author = {Beier, J and Anthes, N and Wahl, J and Harvati, K}, title = {Similar cranial trauma prevalence among Neanderthals and Upper Palaeolithic modern humans.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {686-690}, doi = {10.1038/s41586-018-0696-8}, pmid = {30429606}, issn = {1476-4687}, abstract = {Neanderthals are commonly depicted as leading dangerous lives and permanently struggling for survival. This view largely relies on the high incidences of trauma that have been reported1,2 and have variously been attributed to violent social behaviour3,4, highly mobile hunter-gatherer lifestyles2 or attacks by carnivores5. The described Neanderthal pattern of predominantly cranial injuries is further thought to reflect violent encounters with large prey mammals, resulting from the use of close-range hunting weapons1. These interpretations directly shape our understanding of Neanderthal lifestyles, health and hunting abilities, yet mainly rest on descriptive, case-based evidence. Quantitative, population-level studies of traumatic injuries are rare. Here we reassess the hypothesis of higher cranial trauma prevalence among Neanderthals using a population-level approach-accounting for preservation bias and other contextual data-and an exhaustive fossil database. We show that Neanderthals and early Upper Palaeolithic anatomically modern humans exhibit similar overall incidences of cranial trauma, which are higher for males in both taxa, consistent with patterns shown by later populations of modern humans. Beyond these similarities, we observed species-specific, age-related variation in trauma prevalence, suggesting that there were differences in the timing of injuries during life or that there was a differential mortality risk of trauma survivors in the two groups. Finally, our results highlight the importance of preservation bias in studies of trauma prevalence.}, } @article {pmid30429575, year = {2018}, author = {Evangelou, E and Warren, HR and Mosen-Ansorena, D and Mifsud, B and Pazoki, R and Gao, H and Ntritsos, G and Dimou, N and Cabrera, CP and Karaman, I and Ng, FL and Evangelou, M and Witkowska, K and Tzanis, E and Hellwege, JN and Giri, A and Velez Edwards, DR and Sun, YV and Cho, K and Gaziano, JM and Wilson, PWF and Tsao, PS and Kovesdy, CP and Esko, T and Mägi, R and Milani, L and Almgren, P and Boutin, T and Debette, S and Ding, J and Giulianini, F and Holliday, EG and Jackson, AU and Li-Gao, R and Lin, WY and Luan, J and Mangino, M and Oldmeadow, C and Prins, BP and Qian, Y and Sargurupremraj, M and Shah, N and Surendran, P and Thériault, S and Verweij, N and Willems, SM and Zhao, JH and Amouyel, P and Connell, J and de Mutsert, R and Doney, ASF and Farrall, M and Menni, C and Morris, AD and Noordam, R and Paré, G and Poulter, NR and Shields, DC and Stanton, A and Thom, S and Abecasis, G and Amin, N and Arking, DE and Ayers, KL and Barbieri, CM and Batini, C and Bis, JC and Blake, T and Bochud, M and Boehnke, M and Boerwinkle, E and Boomsma, DI and Bottinger, EP and Braund, PS and Brumat, M and Campbell, A and Campbell, H and Chakravarti, A and Chambers, JC and Chauhan, G and Ciullo, M and Cocca, M and Collins, F and Cordell, HJ and Davies, G and de Borst, MH and de Geus, EJ and Deary, IJ and Deelen, J and Del Greco M, F and Demirkale, CY and Dörr, M and Ehret, GB and Elosua, R and Enroth, S and Erzurumluoglu, AM and Ferreira, T and Frånberg, M and Franco, OH and Gandin, I and Gasparini, P and Giedraitis, V and Gieger, C and Girotto, G and Goel, A and Gow, AJ and Gudnason, V and Guo, X and Gyllensten, U and Hamsten, A and Harris, TB and Harris, SE and Hartman, CA and Havulinna, AS and Hicks, AA and Hofer, E and Hofman, A and Hottenga, JJ and Huffman, JE and Hwang, SJ and Ingelsson, E and James, A and Jansen, R and Jarvelin, MR and Joehanes, R and Johansson, Å and Johnson, AD and Joshi, PK and Jousilahti, P and Jukema, JW and Jula, A and Kähönen, M and Kathiresan, S and Keavney, BD and Khaw, KT and Knekt, P and Knight, J and Kolcic, I and Kooner, JS and Koskinen, S and Kristiansson, K and Kutalik, Z and Laan, M and Larson, M and Launer, LJ and Lehne, B and Lehtimäki, T and Liewald, DCM and Lin, L and Lind, L and Lindgren, CM and Liu, Y and Loos, RJF and Lopez, LM and Lu, Y and Lyytikäinen, LP and Mahajan, A and Mamasoula, C and Marrugat, J and Marten, J and Milaneschi, Y and Morgan, A and Morris, AP and Morrison, AC and Munson, PJ and Nalls, MA and Nandakumar, P and Nelson, CP and Niiranen, T and Nolte, IM and Nutile, T and Oldehinkel, AJ and Oostra, BA and O'Reilly, PF and Org, E and Padmanabhan, S and Palmas, W and Palotie, A and Pattie, A and Penninx, BWJH and Perola, M and Peters, A and Polasek, O and Pramstaller, PP and Nguyen, QT and Raitakari, OT and Ren, M and Rettig, R and Rice, K and Ridker, PM and Ried, JS and Riese, H and Ripatti, S and Robino, A and Rose, LM and Rotter, JI and Rudan, I and Ruggiero, D and Saba, Y and Sala, CF and Salomaa, V and Samani, NJ and Sarin, AP and Schmidt, R and Schmidt, H and Shrine, N and Siscovick, D and Smith, AV and Snieder, H and Sõber, S and Sorice, R and Starr, JM and Stott, DJ and Strachan, DP and Strawbridge, RJ and Sundström, J and Swertz, MA and Taylor, KD and Teumer, A and Tobin, MD and Tomaszewski, M and Toniolo, D and Traglia, M and Trompet, S and Tuomilehto, J and Tzourio, C and Uitterlinden, AG and Vaez, A and van der Most, PJ and van Duijn, CM and Vergnaud, AC and Verwoert, GC and Vitart, V and Völker, U and Vollenweider, P and Vuckovic, D and Watkins, H and Wild, SH and Willemsen, G and Wilson, JF and Wright, AF and Yao, J and Zemunik, T and Zhang, W and Attia, JR and Butterworth, AS and Chasman, DI and Conen, D and Cucca, F and Danesh, J and Hayward, C and Howson, JMM and Laakso, M and Lakatta, EG and Langenberg, C and Melander, O and Mook-Kanamori, DO and Palmer, CNA and Risch, L and Scott, RA and Scott, RJ and Sever, P and Spector, TD and van der Harst, P and Wareham, NJ and Zeggini, E and Levy, D and Munroe, PB and Newton-Cheh, C and Brown, MJ and Metspalu, A and Hung, AM and O'Donnell, CJ and Edwards, TL and , and Psaty, BM and Tzoulaki, I and Barnes, MR and Wain, LV and Elliott, P and Caulfield, MJ}, title = {Publisher Correction: Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1755}, doi = {10.1038/s41588-018-0297-3}, pmid = {30429575}, issn = {1546-1718}, abstract = {In the version of this article originally published, the name of author Martin H. de Borst was coded incorrectly in the XML. The error has now been corrected in the HTML version of the paper.}, } @article {pmid30429573, year = {2018}, author = {}, title = {Keystone pipeline blocked, statistics prize and horse cull.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {298-299}, doi = {10.1038/d41586-018-07349-2}, pmid = {30429573}, issn = {1476-4687}, } @article {pmid30429572, year = {2018}, author = {Abbott, A}, title = {In the Palestinian territories, science struggles against all odds.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {308-311}, doi = {10.1038/d41586-018-07350-9}, pmid = {30429572}, issn = {1476-4687}, } @article {pmid30429571, year = {2018}, author = {Eisenstein, M}, title = {Lymphoma: 4 big questions.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S55}, doi = {10.1038/d41586-018-07367-0}, pmid = {30429571}, issn = {1476-4687}, } @article {pmid30429570, year = {2018}, author = {Ainsworth, C}, title = {Building a better lymphoma vaccine.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S52-S54}, doi = {10.1038/d41586-018-07366-1}, pmid = {30429570}, issn = {1476-4687}, } @article {pmid30429569, year = {2018}, author = {DeWeerdt, S}, title = {How dogs are teaching researchers new tricks for treating cancer.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S50-S51}, doi = {10.1038/d41586-018-07365-2}, pmid = {30429569}, issn = {1476-4687}, } @article {pmid30429568, year = {2018}, author = {Nogrady, B}, title = {Genetically modified T cells target lymphoma.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S42-S43}, doi = {10.1038/d41586-018-07361-6}, pmid = {30429568}, issn = {1476-4687}, } @article {pmid30429567, year = {2018}, author = {Drew, L}, title = {Towards the better diagnosis of lymphoma.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S38-S40}, doi = {10.1038/d41586-018-07360-7}, pmid = {30429567}, issn = {1476-4687}, } @article {pmid30429566, year = {2018}, author = {Dolgin, E}, title = {Precision therapies take aim at non-Hodgkin's lymphoma.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S46-S47}, doi = {10.1038/d41586-018-07363-4}, pmid = {30429566}, issn = {1476-4687}, } @article {pmid30429565, year = {2018}, author = {Eisenstein, M}, title = {The cost of surviving cancer.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S44-S45}, doi = {10.1038/d41586-018-07362-5}, pmid = {30429565}, issn = {1476-4687}, } @article {pmid30429564, year = {2018}, author = {Arney, K}, title = {Solving lymphoma's stem-cell problem.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S48-S49}, doi = {10.1038/d41586-018-07364-3}, pmid = {30429564}, issn = {1476-4687}, } @article {pmid30429563, year = {2018}, author = {Brody, H}, title = {Lymphoma.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {S37}, doi = {10.1038/d41586-018-07359-0}, pmid = {30429563}, issn = {1476-4687}, } @article {pmid30429562, year = {2018}, author = {Shillington, DJ}, title = {Water takes a deep dive into an oceanic tectonic plate.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {335-336}, doi = {10.1038/d41586-018-07335-8}, pmid = {30429562}, issn = {1476-4687}, mesh = {*Water ; }, } @article {pmid30429561, year = {2018}, author = {Rajagopalan, S and Long, EO}, title = {Cell atlas reveals the landscape of early pregnancy.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {337-338}, doi = {10.1038/d41586-018-07317-w}, pmid = {30429561}, issn = {1476-4687}, mesh = {*Gene Expression Profiling ; Humans ; Pregnancy ; *Transcriptome ; }, } @article {pmid30429560, year = {2018}, author = {Díaz, RF}, title = {A key piece in the exoplanet puzzle.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {329-330}, doi = {10.1038/d41586-018-07328-7}, pmid = {30429560}, issn = {1476-4687}, mesh = {Earth (Planet) ; *Planets ; *Snow ; }, } @article {pmid30429559, year = {2018}, author = {Marin da Fonte, LF}, title = {3D print so more scholars can access unique specimens.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {325}, doi = {10.1038/d41586-018-07385-y}, pmid = {30429559}, issn = {1476-4687}, } @article {pmid30429558, year = {2018}, author = {Bernstein, E and Meissner, A and Ramalho-Santos, M}, title = {Paying PIs from grants blocks talent and diversity.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {325}, doi = {10.1038/d41586-018-07382-1}, pmid = {30429558}, issn = {1476-4687}, mesh = {Biomedical Research ; Financing, Organized ; *National Institutes of Health (U.S.) ; Salaries and Fringe Benefits ; United States ; *Workforce ; }, } @article {pmid30429557, year = {2018}, author = {Hagerty, S and Barger, N and Taylor, S and Carter, J and Gruber, J}, title = {Written lab agreements improve mentoring.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {325}, doi = {10.1038/d41586-018-07383-0}, pmid = {30429557}, issn = {1476-4687}, } @article {pmid30429556, year = {2018}, author = {Baghi, HB}, title = {Networks and mentors help female scientists in Africa and Middle East.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {325}, doi = {10.1038/d41586-018-07381-2}, pmid = {30429556}, issn = {1476-4687}, } @article {pmid30429555, year = {2018}, author = {Lymbery, P}, title = {Governments should unite to curb meat consumption.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {325}, doi = {10.1038/d41586-018-07384-z}, pmid = {30429555}, issn = {1476-4687}, } @article {pmid30429554, year = {2018}, author = {Lingen, M}, title = {Say it with mastodons.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {436}, doi = {10.1038/d41586-018-07338-5}, pmid = {30429554}, issn = {1476-4687}, } @article {pmid30429553, year = {2018}, author = {Sohn, E}, title = {How to turn your interests into a career.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {431-433}, doi = {10.1038/d41586-018-07357-2}, pmid = {30429553}, issn = {1476-4687}, } @article {pmid30429552, year = {2018}, author = {Ribas, I and Tuomi, M and Reiners, A and Butler, RP and Morales, JC and Perger, M and Dreizler, S and Rodríguez-López, C and González Hernández, JI and Rosich, A and Feng, F and Trifonov, T and Vogt, SS and Caballero, JA and Hatzes, A and Herrero, E and Jeffers, SV and Lafarga, M and Murgas, F and Nelson, RP and Rodríguez, E and Strachan, JBP and Tal-Or, L and Teske, J and Toledo-Padrón, B and Zechmeister, M and Quirrenbach, A and Amado, PJ and Azzaro, M and Béjar, VJS and Barnes, JR and Berdiñas, ZM and Burt, J and Coleman, G and Cortés-Contreras, M and Crane, J and Engle, SG and Guinan, EF and Haswell, CA and Henning, T and Holden, B and Jenkins, J and Jones, HRA and Kaminski, A and Kiraga, M and Kürster, M and Lee, MH and López-González, MJ and Montes, D and Morin, J and Ofir, A and Pallé, E and Rebolo, R and Reffert, S and Schweitzer, A and Seifert, W and Shectman, SA and Staab, D and Street, RA and Suárez Mascareño, A and Tsapras, Y and Wang, SX and Anglada-Escudé, G}, title = {A candidate super-Earth planet orbiting near the snow line of Barnard's star.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {365-368}, doi = {10.1038/s41586-018-0677-y}, pmid = {30429552}, issn = {1476-4687}, abstract = {Barnard's star is a red dwarf, and has the largest proper motion (apparent motion across the sky) of all known stars. At a distance of 1.8 parsecs1, it is the closest single star to the Sun; only the three stars in the α Centauri system are closer. Barnard's star is also among the least magnetically active red dwarfs known2,3 and has an estimated age older than the Solar System. Its properties make it a prime target for planetary searches; various techniques with different sensitivity limits have been used previously, including radial-velocity imaging4-6, astrometry7,8 and direct imaging9, but all ultimately led to negative or null results. Here we combine numerous measurements from high-precision radial-velocity instruments, revealing the presence of a low-amplitude periodic signal with a period of 233 days. Independent photometric and spectroscopic monitoring, as well as an analysis of instrumental systematic effects, suggest that this signal is best explained as arising from a planetary companion. The candidate planet around Barnard's star is a cold super-Earth, with a minimum mass of 3.2 times that of Earth, orbiting near its snow line (the minimum distance from the star at which volatile compounds could condense). The combination of all radial-velocity datasets spanning 20 years of measurements additionally reveals a long-term modulation that could arise from a stellar magnetic-activity cycle or from a more distant planetary object. Because of its proximity to the Sun, the candidate planet has a maximum angular separation of 220 milliarcseconds from Barnard's star, making it an excellent target for direct imaging and astrometric observations in the future.}, } @article {pmid30429551, year = {2018}, author = {Zhang, W and Villarini, G and Vecchi, GA and Smith, JA}, title = {Urbanization exacerbated the rainfall and flooding caused by hurricane Harvey in Houston.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {384-388}, doi = {10.1038/s41586-018-0676-z}, pmid = {30429551}, issn = {1476-4687}, support = {AGS-1349827//National Science Foundation/International ; EAR-1520683//National Science Foundation/International ; AGS-1522492/AG/NIA NIH HHS/United States ; CBET-1444758//National lScience Foundation/International ; }, abstract = {Category 4 landfalling hurricane Harvey poured more than a metre of rainfall across the heavily populated Houston area, leading to unprecedented flooding and damage. Although studies have focused on the contribution of anthropogenic climate change to this extreme rainfall event1-3, limited attention has been paid to the potential effects of urbanization on the hydrometeorology associated with hurricane Harvey. Here we find that urbanization exacerbated not only the flood response but also the storm total rainfall. Using the Weather Research and Forecast model-a numerical model for simulating weather and climate at regional scales-and statistical models, we quantify the contribution of urbanization to rainfall and flooding. Overall, we find that the probability of such extreme flood events across the studied basins increased on average by about 21 times in the period 25-30 August 2017 because of urbanization. The effect of urbanization on storm-induced extreme precipitation and flooding should be more explicitly included in global climate models, and this study highlights its importance when assessing the future risk of such extreme events in highly urbanized coastal areas.}, } @article {pmid30429550, year = {2018}, author = {Patricola, CM and Wehner, MF}, title = {Anthropogenic influences on major tropical cyclone events.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {339-346}, doi = {10.1038/s41586-018-0673-2}, pmid = {30429550}, issn = {1476-4687}, support = {DE-AC02-05CH11231//US Department of Energy/International ; }, abstract = {There is no consensus on whether climate change has yet affected the statistics of tropical cyclones, owing to their large natural variability and the limited period of consistent observations. In addition, projections of future tropical cyclone activity are uncertain, because they often rely on coarse-resolution climate models that parameterize convection and hence have difficulty in directly representing tropical cyclones. Here we used convection-permitting regional climate model simulations to investigate whether and how recent destructive tropical cyclones would change if these events had occurred in pre-industrial and in future climates. We found that, relative to pre-industrial conditions, climate change so far has enhanced the average and extreme rainfall of hurricanes Katrina, Irma and Maria, but did not change tropical cyclone wind-speed intensity. In addition, future anthropogenic warming would robustly increase the wind speed and rainfall of 11 of 13 intense tropical cyclones (of 15 events sampled globally). Additional regional climate model simulations suggest that convective parameterization introduces minimal uncertainty into the sign of projected changes in tropical cyclone intensity and rainfall, which allows us to have confidence in projections from global models with parameterized convection and resolution fine enough to include tropical cyclones.}, } @article {pmid30429549, year = {2018}, author = {Cai, C and Wiens, DA and Shen, W and Eimer, M}, title = {Water input into the Mariana subduction zone estimated from ocean-bottom seismic data.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {389-392}, doi = {10.1038/s41586-018-0655-4}, pmid = {30429549}, issn = {1476-4687}, support = {OCE-0841074//Natioinal Science Foundation/International ; }, abstract = {The water cycle at subduction zones remains poorly understood, although subduction is the only mechanism for water transport deep into Earth. Previous estimates of water flux1-3 exhibit large variations in the amount of water that is subducted deeper than 100 kilometres. The main source of uncertainty in these calculations is the initial water content of the subducting uppermost mantle. Previous active-source seismic studies suggest that the subducting slab may be pervasively hydrated in the plate-bending region near the oceanic trench4-7. However, these studies do not constrain the depth extent of hydration and most investigate young incoming plates, leaving subduction-zone water budgets for old subducting plates uncertain. Here we present seismic images of the crust and uppermost mantle around the central Mariana trench derived from Rayleigh-wave analysis of broadband ocean-bottom seismic data. These images show that the low mantle velocities that result from mantle hydration extend roughly 24 kilometres beneath the Moho discontinuity. Combined with estimates of subducting crustal water, these results indicate that at least 4.3 times more water subducts than previously calculated for this region3. If other old, cold subducting slabs contain correspondingly thick layers of hydrous mantle, as suggested by the similarity of incoming plate faulting across old, cold subducting slabs, then estimates of the global water flux into the mantle at depths greater than 100 kilometres must be increased by a factor of about three compared to previous estimates3. Because a long-term net influx of water to the deep interior of Earth is inconsistent with the geological record8, estimates of water expelled at volcanic arcs and backarc basins probably also need to be revised upwards9.}, } @article {pmid30429548, year = {2018}, author = {Vento-Tormo, R and Efremova, M and Botting, RA and Turco, MY and Vento-Tormo, M and Meyer, KB and Park, JE and Stephenson, E and Polański, K and Goncalves, A and Gardner, L and Holmqvist, S and Henriksson, J and Zou, A and Sharkey, AM and Millar, B and Innes, B and Wood, L and Wilbrey-Clark, A and Payne, RP and Ivarsson, MA and Lisgo, S and Filby, A and Rowitch, DH and Bulmer, JN and Wright, GJ and Stubbington, MJT and Haniffa, M and Moffett, A and Teichmann, SA}, title = {Single-cell reconstruction of the early maternal-fetal interface in humans.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {347-353}, doi = {10.1038/s41586-018-0698-6}, pmid = {30429548}, issn = {1476-4687}, support = {MR/R006237/1//Wellcome Trust/United Kingdom ; }, abstract = {During early human pregnancy the uterine mucosa transforms into the decidua, into which the fetal placenta implants and where placental trophoblast cells intermingle and communicate with maternal cells. Trophoblast-decidual interactions underlie common diseases of pregnancy, including pre-eclampsia and stillbirth. Here we profile the transcriptomes of about 70,000 single cells from first-trimester placentas with matched maternal blood and decidual cells. The cellular composition of human decidua reveals subsets of perivascular and stromal cells that are located in distinct decidual layers. There are three major subsets of decidual natural killer cells that have distinctive immunomodulatory and chemokine profiles. We develop a repository of ligand-receptor complexes and a statistical tool to predict the cell-type specificity of cell-cell communication via these molecular interactions. Our data identify many regulatory interactions that prevent harmful innate or adaptive immune responses in this environment. Our single-cell atlas of the maternal-fetal interface reveals the cellular organization of the decidua and placenta, and the interactions that are critical for placentation and reproductive success.}, } @article {pmid30429547, year = {2018}, author = {Samant, RS and Livingston, CM and Sontag, EM and Frydman, J}, title = {Distinct proteostasis circuits cooperate in nuclear and cytoplasmic protein quality control.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {407-411}, doi = {10.1038/s41586-018-0678-x}, pmid = {30429547}, issn = {1476-4687}, support = {1F32CA162919-01A1/CA/NCI NIH HHS/United States ; R37 GM056433/GM/NIGMS NIH HHS/United States ; F32 NS086253/NS/NINDS NIH HHS/United States ; }, abstract = {Protein misfolding is linked to a wide array of human disorders, including Alzheimer's disease, Parkinson's disease and type II diabetes1,2. Protective cellular protein quality control (PQC) mechanisms have evolved to selectively recognize misfolded proteins and limit their toxic effects3-9, thus contributing to the maintenance of the proteome (proteostasis). Here we examine how molecular chaperones and the ubiquitin-proteasome system cooperate to recognize and promote the clearance of soluble misfolded proteins. Using a panel of PQC substrates with distinct characteristics and localizations, we define distinct chaperone and ubiquitination circuitries that execute quality control in the cytoplasm and nucleus. In the cytoplasm, proteasomal degradation of misfolded proteins requires tagging with mixed lysine 48 (K48)- and lysine 11 (K11)-linked ubiquitin chains. A distinct combination of E3 ubiquitin ligases and specific chaperones is required to achieve each type of linkage-specific ubiquitination. In the nucleus, however, proteasomal degradation of misfolded proteins requires only K48-linked ubiquitin chains, and is thus independent of K11-specific ligases and chaperones. The distinct ubiquitin codes for nuclear and cytoplasmic PQC appear to be linked to the function of the ubiquilin protein Dsk2, which is specifically required to clear nuclear misfolded proteins. Our work defines the principles of cytoplasmic and nuclear PQC as distinct, involving combinatorial recognition by defined sets of cooperating chaperones and E3 ligases. A better understanding of how these organelle-specific PQC requirements implement proteome integrity has implications for our understanding of diseases linked to impaired protein clearance and proteostasis dysfunction.}, } @article {pmid30429546, year = {2018}, author = {Thume, K and Gebser, B and Chen, L and Meyer, N and Kieber, DJ and Pohnert, G}, title = {The metabolite dimethylsulfoxonium propionate extends the marine organosulfur cycle.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {412-415}, doi = {10.1038/s41586-018-0675-0}, pmid = {30429546}, issn = {1476-4687}, support = {OCE-1756907//National Science Foundation/International ; }, abstract = {Algae produce massive amounts of dimethylsulfoniopropionate (DMSP), which fuel the organosulfur cycle1,2. On a global scale, several petagrams of this sulfur species are produced annually, thereby driving fundamental processes and the marine food web1. An important DMSP transformation product is dimethylsulfide, which can be either emitted to the atmosphere3,4 or oxidized to dimethylsulfoxide (DMSO) and other products5. Here we report the discovery of a structurally unusual metabolite, dimethylsulfoxonium propionate (DMSOP), that is synthesized by several DMSP-producing microalgae and marine bacteria. As with DMSP, DMSOP is a low-molecular-weight zwitterionic metabolite that carries both a positively and a negatively charged functional group. Isotope labelling studies demonstrate that DMSOP is produced from DMSP, and is readily metabolized to DMSO by marine bacteria. DMSOP was found in near nanomolar amounts in field samples and in algal culture media, and thus represents-to our knowledge-a previously undescribed biogenic source for DMSO in the marine environment. The estimated annual oceanic production of oxidized sulfur from this pathway is in the teragram range, similar to the calculated dimethylsulfide flux to the atmosphere3. This sulfoxonium metabolite is therefore a key metabolite of a previously undescribed pathway in the marine sulfur cycle. These findings highlight the importance of DMSOP in the marine organosulfur cycle.}, } @article {pmid30429545, year = {2018}, author = {Srinivas, V and Lebrette, H and Lundin, D and Kutin, Y and Sahlin, M and Lerche, M and Eirich, J and Branca, RMM and Cox, N and Sjöberg, BM and Högbom, M}, title = {Metal-free ribonucleotide reduction powered by a DOPA radical in Mycoplasma pathogens.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {416-420}, doi = {10.1038/s41586-018-0653-6}, pmid = {30429545}, issn = {1476-4687}, abstract = {Ribonucleotide reductase (RNR) catalyses the only known de novo pathway for the production of all four deoxyribonucleotides that are required for DNA synthesis1,2. It is essential for all organisms that use DNA as their genetic material and is a current drug target3,4. Since the discovery that iron is required for function in the aerobic, class I RNR found in all eukaryotes and many bacteria, a dinuclear metal site has been viewed as necessary to generate and stabilize the catalytic radical that is essential for RNR activity5-7. Here we describe a group of RNR proteins in Mollicutes-including Mycoplasma pathogens-that possess a metal-independent stable radical residing on a modified tyrosyl residue. Structural, biochemical and spectroscopic characterization reveal a stable 3,4-dihydroxyphenylalanine (DOPA) radical species that directly supports ribonucleotide reduction in vitro and in vivo. This observation overturns the presumed requirement for a dinuclear metal site in aerobic ribonucleotide reductase. The metal-independent radical requires new mechanisms for radical generation and stabilization, processes that are targeted by RNR inhibitors. It is possible that this RNR variant provides an advantage under metal starvation induced by the immune system. Organisms that encode this type of RNR-some of which are developing resistance to antibiotics-are involved in diseases of the respiratory, urinary and genital tracts. Further characterization of this RNR family and its mechanism of cofactor generation will provide insight into new enzymatic chemistry and be of value in devising strategies to combat the pathogens that utilize it. We propose that this RNR subclass is denoted class Ie.}, } @article {pmid30429544, year = {2018}, author = {Goban, A and Hutson, RB and Marti, GE and Campbell, SL and Perlin, MA and Julienne, PS and D'Incao, JP and Rey, AM and Ye, J}, title = {Emergence of multi-body interactions in a fermionic lattice clock.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {369-373}, doi = {10.1038/s41586-018-0661-6}, pmid = {30429544}, issn = {1476-4687}, support = {NSF-1734006//National Science Foundation/International ; PHY-1607204//National Science Foundation/International ; }, abstract = {Alkaline-earth atoms have metastable 'clock' states with minute-long optical lifetimes, high-spin nuclei and SU(N)-symmetric interactions, making them powerful platforms for atomic clocks1, quantum information processing2 and quantum simulation3. Few-particle systems of such atoms provide opportunities to observe the emergence of complex many-body phenomena with increasing system size4. Multi-body interactions among particles are emergent phenomena, which cannot be broken down into sums over underlying pairwise interactions. They could potentially be used to create exotic states of quantum matter5,6, but have yet to be explored in ultracold fermions. Here we create arrays of isolated few-body systems in an optical clock based on a three-dimensional lattice of fermionic 87Sr atoms. We use high-resolution clock spectroscopy to directly observe the onset of elastic and inelastic multi-body interactions among atoms. We measure the frequency shifts of the clock transition for varying numbers of atoms per lattice site, from n = 1 to n = 5, and observe nonlinear interaction shifts characteristic of elastic multi-body effects. These measurements, combined with theory, elucidate an emergence of SU(N)-symmetric multi-body interactions, which are unique to fermionic alkaline-earth atoms. To study inelastic multi-body effects, we use these frequency shifts to isolate n-occupied sites in the lattice and measure the corresponding lifetimes of the clock states. This allows us to access the short-range few-body physics without experiencing the systematic effects that are encountered in a bulk gas. The lifetimes that we measure in the isolated few-body systems agree very well with numerical predictions based on a simple model for the interatomic potential, suggesting a universality in ultracold collisions. By connecting these few-body systems through tunnelling, the favourable energy and timescales of the interactions will allow our system to be used for studies of high-spin quantum magnetism7,8 and the Kondo effect3,9.}, } @article {pmid30429543, year = {2018}, author = {Hepting, M and Chaix, L and Huang, EW and Fumagalli, R and Peng, YY and Moritz, B and Kummer, K and Brookes, NB and Lee, WC and Hashimoto, M and Sarkar, T and He, JF and Rotundu, CR and Lee, YS and Greene, RL and Braicovich, L and Ghiringhelli, G and Shen, ZX and Devereaux, TP and Lee, WS}, title = {Three-dimensional collective charge excitations in electron-doped copper oxide superconductors.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {374-378}, doi = {10.1038/s41586-018-0648-3}, pmid = {30429543}, issn = {1476-4687}, support = {DE-AC02-76SF00515//US Department of Energy/International ; DMR-1708334//National Science Foundation/International ; DE-AC02-05CH11231//Department of Energy/International ; }, abstract = {High-temperature copper oxide superconductors consist of stacked CuO2 planes, with electronic band structures and magnetic excitations that are primarily two-dimensional1,2, but with superconducting coherence that is three-dimensional. This dichotomy highlights the importance of out-of-plane charge dynamics, which has been found to be incoherent in the normal state3,4 within the limited range of momenta accessible by optics. Here we use resonant inelastic X-ray scattering to explore the charge dynamics across all three dimensions of the Brillouin zone. Polarization analysis of recently discovered collective excitations (modes) in electron-doped copper oxides5-7 reveals their charge origin, that is, without mixing with magnetic components5-7. The excitations disperse along both the in-plane and out-of-plane directions, revealing its three-dimensional nature. The periodicity of the out-of-plane dispersion corresponds to the distance between neighbouring CuO2 planes rather than to the crystallographic c-axis lattice constant, suggesting that the interplane Coulomb interaction is responsible for the coherent out-of-plane charge dynamics. The observed properties are hallmarks of the long-sought 'acoustic plasmon', which is a branch of distinct charge collective modes predicted for layered systems8-12 and argued to play a substantial part in mediating high-temperature superconductivity10-12.}, } @article {pmid30429333, year = {2018}, author = {Snyder, BER and Bols, ML and Rhoda, HM and Vanelderen, P and Böttger, LH and Braun, A and Yan, JJ and Hadt, RG and Babicz, JT and Hu, MY and Zhao, J and Alp, EE and Hedman, B and Hodgson, KO and Schoonheydt, RA and Sels, BF and Solomon, EI}, title = {Mechanism of selective benzene hydroxylation catalyzed by iron-containing zeolites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12124-12129}, pmid = {30429333}, issn = {1091-6490}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; }, abstract = {A direct, catalytic conversion of benzene to phenol would have wide-reaching economic impacts. Fe zeolites exhibit a remarkable combination of high activity and selectivity in this conversion, leading to their past implementation at the pilot plant level. There were, however, issues related to catalyst deactivation for this process. Mechanistic insight could resolve these issues, and also provide a blueprint for achieving high performance in selective oxidation catalysis. Recently, we demonstrated that the active site of selective hydrocarbon oxidation in Fe zeolites, named α-O, is an unusually reactive Fe(IV)=O species. Here, we apply advanced spectroscopic techniques to determine that the reaction of this Fe(IV)=O intermediate with benzene in fact regenerates the reduced Fe(II) active site, enabling catalytic turnover. At the same time, a small fraction of Fe(III)-phenolate poisoned active sites form, defining a mechanism for catalyst deactivation. Density-functional theory calculations provide further insight into the experimentally defined mechanism. The extreme reactivity of α-O significantly tunes down (eliminates) the rate-limiting barrier for aromatic hydroxylation, leading to a diffusion-limited reaction coordinate. This favors hydroxylation of the rapidly diffusing benzene substrate over the slowly diffusing (but more reactive) oxygenated product, thereby enhancing selectivity. This defines a mechanism to simultaneously attain high activity (conversion) and selectivity, enabling the efficient oxidative upgrading of inert hydrocarbon substrates.}, } @article {pmid30429332, year = {2018}, author = {Hou, J and Shi, X and Chen, C and Islam, MS and Johnson, AF and Kanno, T and Huettel, B and Yen, MR and Hsu, FM and Ji, T and Chen, PY and Matzke, M and Matzke, AJM and Cheng, J and Birchler, JA}, title = {Global impacts of chromosomal imbalance on gene expression in Arabidopsis and other taxa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11321-E11330}, pmid = {30429332}, issn = {1091-6490}, abstract = {Changes in dosage of part of the genome (aneuploidy) have long been known to produce much more severe phenotypic consequences than changes in the number of whole genomes (ploidy). To examine the basis of these differences, global gene expression in mature leaf tissue for all five trisomies and in diploids, triploids, and tetraploids of Arabidopsis thaliana was studied. The trisomies displayed a greater spread of expression modulation than the ploidy series. In general, expression of genes on the varied chromosome ranged from compensation to dosage effect, whereas genes from the remainder of the genome ranged from no effect to reduced expression approaching the inverse level of chromosomal imbalance (2/3). Genome-wide DNA methylation was examined in each genotype and found to shift most prominently with trisomy 4 but otherwise exhibited little change, indicating that genetic imbalance is generally mechanistically unrelated to DNA methylation. Independent analysis of gene functional classes demonstrated that ribosomal, proteasomal, and gene body methylated genes were less modulated compared with all classes of genes, whereas transcription factors, signal transduction components, and organelle-targeted protein genes were more tightly inversely affected. Comparing transcription factors and their targets in the trisomies and in expression networks revealed considerable discordance, illustrating that altered regulatory stoichiometry is a major contributor to genetic imbalance. Reanalysis of published data on gene expression in disomic yeast and trisomic mouse cells detected similar stoichiometric effects across broad phylogenetic taxa, and indicated that these effects reflect normal gene regulatory processes.}, } @article {pmid30429331, year = {2018}, author = {Ando, H and Hirose, M and Mikoshiba, K}, title = {Aberrant IP3 receptor activities revealed by comprehensive analysis of pathological mutations causing spinocerebellar ataxia 29.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12259-12264}, pmid = {30429331}, issn = {1091-6490}, abstract = {Spinocerebellar ataxia type 29 (SCA29) is autosomal dominant congenital ataxia characterized by early-onset motor delay, hypotonia, and gait ataxia. Recently, heterozygous missense mutations in an intracellular Ca2+ channel, inositol 1,4,5-trisphosphate (IP3) receptor type 1 (IP3R1), were identified as a cause of SCA29. However, the functional impacts of these mutations remain largely unknown. Here, we determined the molecular mechanisms by which pathological mutations affect IP3R1 activity and Ca2+ dynamics. Ca2+ imaging using IP3R-null HeLa cells generated by genome editing revealed that all SCA29 mutations identified within or near the IP3-binding domain of IP3R1 completely abolished channel activity. Among these mutations, R241K, T267M, T267R, R269G, R269W, S277I, K279E, A280D, and E497K impaired IP3 binding to IP3R1, whereas the T579I and N587D mutations disrupted channel activity without affecting IP3 binding, suggesting that T579I and N587D compromise channel gating mechanisms. Carbonic anhydrase-related protein VIII (CA8) is an IP3R1-regulating protein abundantly expressed in cerebellar Purkinje cells and is a causative gene of congenital ataxia. The SCA29 mutation V1538M within the CA8-binding site of IP3R1 completely eliminated its interaction with CA8 and CA8-mediated IP3R1 inhibition. Furthermore, pathological mutations in CA8 decreased CA8-mediated suppression of IP3R1 by reducing protein stability and the interaction with IP3R1. These results demonstrated the mechanisms by which pathological mutations cause IP3R1 dysfunction, i.e., the disruption of IP3 binding, IP3-mediated gating, and regulation via the IP3R-modulatory protein. The resulting aberrant Ca2+ homeostasis may contribute to the pathogenesis of cerebellar ataxia.}, } @article {pmid30429330, year = {2018}, author = {Barth, A and Hendrix, J and Fried, D and Barak, Y and Bayer, EA and Lamb, DC}, title = {Dynamic interactions of type I cohesin modules fine-tune the structure of the cellulosome of Clostridium thermocellum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11274-E11283}, pmid = {30429330}, issn = {1091-6490}, abstract = {Efficient degradation of plant cell walls by selected anaerobic bacteria is performed by large extracellular multienzyme complexes termed cellulosomes. The spatial arrangement within the cellulosome is organized by a protein called scaffoldin, which recruits the cellulolytic subunits through interactions between cohesin modules on the scaffoldin and dockerin modules on the enzymes. Although many structural studies of the individual components of cellulosomal scaffoldins have been performed, the role of interactions between individual cohesin modules and the flexible linker regions between them are still not entirely understood. Here, we report single-molecule measurements using FRET to study the conformational dynamics of a bimodular cohesin segment of the scaffoldin protein CipA of Clostridium thermocellum We observe compacted structures in solution that persist on the timescale of milliseconds. The compacted conformation is found to be in dynamic equilibrium with an extended state that shows distance fluctuations on the microsecond timescale. Shortening of the intercohesin linker does not destabilize the interactions but reduces the rate of contact formation. Upon addition of dockerin-containing enzymes, an extension of the flexible state is observed, but the cohesin-cohesin interactions persist. Using all-atom molecular-dynamics simulations of the system, we further identify possible intercohesin binding modes. Beyond the view of scaffoldin as "beads on a string," we propose that cohesin-cohesin interactions are an important factor for the precise spatial arrangement of the enzymatic subunits in the cellulosome that leads to the high catalytic synergy in these assemblies and should be considered when designing cellulosomes for industrial applications.}, } @article {pmid30429329, year = {2018}, author = {Kim, JS and Liu, L and Fitzsimmons, LF and Wang, Y and Crawford, MA and Mastrogiovanni, M and Trujillo, M and Till, JKA and Radi, R and Dai, S and Vázquez-Torres, A}, title = {DksA-DnaJ redox interactions provide a signal for the activation of bacterial RNA polymerase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11780-E11789}, doi = {10.1073/pnas.1813572115}, pmid = {30429329}, issn = {1091-6490}, support = {I01 BX002073/BX/BLRD VA/United States ; R01 AI136520/AI/NIAID NIH HHS/United States ; R56 AI054959/AI/NIAID NIH HHS/United States ; T32 AI052066/AI/NIAID NIH HHS/United States ; F31 AI118223/AI/NIAID NIH HHS/United States ; R01 AI054959/AI/NIAID NIH HHS/United States ; }, abstract = {RNA polymerase is the only known protein partner of the transcriptional regulator DksA. Herein, we demonstrate that the chaperone DnaJ establishes direct, redox-based interactions with oxidized DksA. Cysteine residues in the zinc finger of DksA become oxidized in Salmonella exposed to low concentrations of hydrogen peroxide (H2O2). The resulting disulfide bonds unfold the globular domain of DksA, signaling high-affinity interaction of the C-terminal α-helix to DnaJ. Oxidoreductase and chaperone activities of DnaJ reduce the disulfide bonds of its client and promote productive interactions between DksA and RNA polymerase. Simultaneously, guanosine tetraphosphate (ppGpp), which is synthesized by RelA in response to low concentrations of H2O2, binds at site 2 formed at the interface of DksA and RNA polymerase and synergizes with the DksA/DnaJ redox couple, thus activating the transcription of genes involved in amino acid biosynthesis and transport. However, the high concentrations of ppGpp produced by Salmonella experiencing oxidative stress oppose DksA/DnaJ-dependent transcription. Cumulatively, the interplay of DksA, DnaJ, and ppGpp on RNA polymerase protects Salmonella from the antimicrobial activity of the NADPH phagocyte oxidase. Our research has identified redox-based signaling that activates the transcriptional activity of the RNA polymerase regulator DksA.}, } @article {pmid30429328, year = {2018}, author = {Yang, K and Park, D and Tretyakova, NY and Greenberg, MM}, title = {Histone tails decrease N7-methyl-2'-deoxyguanosine depurination and yield DNA-protein cross-links in nucleosome core particles and cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11212-E11220}, pmid = {30429328}, issn = {1091-6490}, support = {R01 ES023350/ES/NIEHS NIH HHS/United States ; R01 GM063028/GM/NIGMS NIH HHS/United States ; }, abstract = {Monofunctional alkylating agents preferentially react at the N7 position of 2'-deoxyguanosine in duplex DNA. Methylated DNA, such as that produced by methyl methanesulfonate (MMS) and temozolomide, exists for days in organisms. The predominant consequence of N7-methyl-2'-deoxyguanosine (MdG) is widely believed to be abasic site (AP) formation via hydrolysis, a process that is slow in free DNA. Examination of MdG reactivity within nucleosome core particles (NCPs) provided two general observations. MdG depurination rate constants are reduced in NCPs compared with when the identical DNA sequence is free in solution. The magnitude of the decrease correlates with proximity to the positively charged histone tails, and experiments in NCPs containing histone variants reveal that positively charged amino acids are responsible for the decreased rate of abasic site formation from MdG. In addition, the lysine-rich histone tails form DNA-protein cross-links (DPCs) with MdG. Cross-link formation is reversible and is ascribed to nucleophilic attack at the C8 position of MdG. DPC and retarded abasic site formation are observed in NCPs randomly damaged by MMS, indicating that these are general processes. Histone-MdG cross-links were also detected by mass spectrometry in chromatin isolated from V79 Chinese hamster lung cells treated with MMS. The formation of DPCs following damage by a monofunctional alkylating agent has not been reported previously. These observations reveal the possibility that such DPCs may contribute to the cytotoxicity of monofunctional alkylating agents, such as MMS, N-methyl-N-nitrosourea, and temozolomide.}, } @article {pmid30429327, year = {2018}, author = {Smith, KL and Ruhl, HA and Huffard, CL and Messié, M and Kahru, M}, title = {Episodic organic carbon fluxes from surface ocean to abyssal depths during long-term monitoring in NE Pacific.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12235-12240}, pmid = {30429327}, issn = {1091-6490}, abstract = {Growing evidence suggests substantial quantities of particulate organic carbon (POC) produced in surface waters reach abyssal depths within days during episodic flux events. A 29-year record of in situ observations was used to examine episodic peaks in POC fluxes and sediment community oxygen consumption (SCOC) at Station M (NE Pacific, 4,000-m depth). From 1989 to 2017, 19% of POC flux at 3,400 m arrived during high-magnitude episodic events (≥mean + 2 σ), and 43% from 2011 to 2017. From 2011 to 2017, when high-resolution SCOC data were available, time lags between changes in satellite-estimated export flux (EF), POC flux, and SCOC on the sea floor varied between six flux events from 0 to 70 days, suggesting variable remineralization rates and/or particle sinking speeds. Half of POC flux pulse events correlated with prior increases in EF and/or subsequent SCOC increases. Peaks in EF overlying Station M frequently translated to changes in POC flux at abyssal depths. A power-law model (Martin curve) was used to estimate abyssal fluxes from EF and midwater temperature variation. While the background POC flux at 3,400-m depth was described well by the model, the episodic events were significantly underestimated by ∼80% and total flux by almost 50%. Quantifying episodic pulses of organic carbon into the deep sea is critical in modeling the depth and intensity of POC sequestration and understanding the global carbon cycle.}, } @article {pmid30429326, year = {2018}, author = {Krause, MD and Huang, RT and Wu, D and Shentu, TP and Harrison, DL and Whalen, MB and Stolze, LK and Di Rienzo, A and Moskowitz, IP and Civelek, M and Romanoski, CE and Fang, Y}, title = {Genetic variant at coronary artery disease and ischemic stroke locus 1p32.2 regulates endothelial responses to hemodynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11349-E11358}, pmid = {30429326}, issn = {1091-6490}, support = {T32 HL007605/HL/NHLBI NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; T32 HL007381/HL/NHLBI NIH HHS/United States ; F32 HL134288/HL/NHLBI NIH HHS/United States ; R01 HL138223/HL/NHLBI NIH HHS/United States ; R00 HL123485/HL/NHLBI NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; R00 HL121172/HL/NHLBI NIH HHS/United States ; R01 HL136765/HL/NHLBI NIH HHS/United States ; }, abstract = {Biomechanical cues dynamically control major cellular processes, but whether genetic variants actively participate in mechanosensing mechanisms remains unexplored. Vascular homeostasis is tightly regulated by hemodynamics. Exposure to disturbed blood flow at arterial sites of branching and bifurcation causes constitutive activation of vascular endothelium contributing to atherosclerosis, the major cause of coronary artery disease (CAD) and ischemic stroke (IS). Conversely, unidirectional flow promotes quiescent endothelium. Genome-wide association studies (GWAS) have identified chromosome 1p32.2 as strongly associated with CAD/IS; however, the causal mechanism related to this locus remains unknown. Using statistical analyses, assay of transposase accessible chromatin with whole-genome sequencing (ATAC-seq), H3K27ac/H3K4me2 ChIP with whole-genome sequencing (ChIP-seq), and CRISPR interference in human aortic endothelial cells (HAECs), our results demonstrate that rs17114036, a common noncoding polymorphism at 1p32.2, is located in an endothelial enhancer dynamically regulated by hemodynamics. CRISPR-Cas9-based genome editing shows that rs17114036-containing region promotes endothelial quiescence under unidirectional shear stress by regulating phospholipid phosphatase 3 (PLPP3). Chromatin accessibility quantitative trait locus (caQTL) mapping using HAECs from 56 donors, allelic imbalance assay from 7 donors, and luciferase assays demonstrate that CAD/IS-protective allele at rs17114036 in PLPP3 intron 5 confers increased endothelial enhancer activity. ChIP-PCR and luciferase assays show that CAD/IS-protective allele at rs17114036 creates a binding site for transcription factor Krüppel-like factor 2 (KLF2), which increases the enhancer activity under unidirectional flow. These results demonstrate that a human SNP contributes to critical endothelial mechanotransduction mechanisms and suggest that human haplotypes and related cis-regulatory elements provide a previously unappreciated layer of regulatory control in cellular mechanosensing mechanisms.}, } @article {pmid30429325, year = {2018}, author = {Cartella, A and Nova, TF and Fechner, M and Merlin, R and Cavalleri, A}, title = {Parametric amplification of optical phonons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12148-12151}, pmid = {30429325}, issn = {1091-6490}, abstract = {We use coherent midinfrared optical pulses to resonantly excite large-amplitude oscillations of the Si-C stretching mode in silicon carbide. When probing the sample with a second pulse, we observe parametric optical gain at all wavelengths throughout the reststrahlen band. This effect reflects the amplification of light by phonon-mediated four-wave mixing and, by extension, of optical-phonon fluctuations. Density functional theory calculations clarify aspects of the microscopic mechanism for this phenomenon. The high-frequency dielectric permittivity and the phonon oscillator strength depend quadratically on the lattice coordinate; they oscillate at twice the frequency of the optical field and provide a parametric drive for the lattice mode. Parametric gain in phononic four-wave mixing is a generic mechanism that can be extended to all polar modes of solids, as a means to control the kinetics of phase transitions, to amplify many-body interactions or to control phonon-polariton waves.}, } @article {pmid30429324, year = {2018}, author = {Bigi, R and Landis, JT and An, H and Caro-Vegas, C and Raab-Traub, N and Dittmer, DP}, title = {Epstein-Barr virus enhances genome maintenance of Kaposi sarcoma-associated herpesvirus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11379-E11387}, pmid = {30429324}, issn = {1091-6490}, support = {P01 CA019014/CA/NCI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 DE018304/DE/NIDCR NIH HHS/United States ; }, abstract = {Primary effusion lymphoma (PEL) is a B cell lymphoma that is always associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and in many cases also with Epstein-Barr virus (EBV); however, the requirement for EBV coinfection is not clear. Here, we demonstrate that adding exogenous EBV to KSHV+ single-positive PEL leads to increased KSHV genome maintenance and KSHV latency-associated nuclear antigen (LANA) expression. To show that EBV was necessary for naturally coinfected PEL, we nucleofected KSHV+/EBV+ PEL cell lines with an EBV-specific CRISPR/Cas9 plasmid to delete EBV and observed a dramatic decrease in cell viability, KSHV genome copy number, and LANA expression. This phenotype was reversed by expressing Epstein-Barr nuclear antigen 1 (EBNA-1) in trans, even though EBNA-1 and LANA do not colocalize in infected cells. This work reveals that EBV EBNA-1 plays an essential role in the pathogenesis of PEL by increasing KSHV viral load and LANA expression.}, } @article {pmid30429323, year = {2018}, author = {Tseng, WC and Pryde, DC and Yoger, KE and Padilla, KM and Antonio, BM and Han, S and Shanmugasundaram, V and Gerlach, AC}, title = {TRPA1 ankyrin repeat six interacts with a small molecule inhibitor chemotype.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12301-12306}, pmid = {30429323}, issn = {1091-6490}, abstract = {TRPA1, a member of the transient receptor potential channel (TRP) family, is genetically linked to pain in humans, and small molecule inhibitors are efficacious in preclinical animal models of inflammatory pain. These findings have driven significant interest in development of selective TRPA1 inhibitors as potential analgesics. The majority of TRPA1 inhibitors characterized to date have been reported to interact with the S5 transmembrane helices forming part of the pore region of the channel. However, the development of many of these inhibitors as clinical drug candidates has been prevented by high lipophilicity, low solubility, and poor pharmacokinetic profiles. Identification of alternate compound interacting sites on TRPA1 provides the opportunity to develop structurally distinct modulators with novel structure-activity relationships and more desirable physiochemical properties. In this paper, we have identified a previously undescribed potent and selective small molecule thiadiazole structural class of TRPA1 inhibitor. Using species ortholog chimeric and mutagenesis strategies, we narrowed down the site of interaction to ankyrinR #6 within the distal N-terminal region of TRPA1. To identify the individual amino acid residues involved, we generated a computational model of the ankyrinR domain. This model was used predictively to identify three critical amino acids in human TRPA1, G238, N249, and K270, which were confirmed by mutagenesis to account for compound activity. These findings establish a small molecule interaction region on TRPA1, expanding potential avenues for developing TRPA1 inhibitor analgesics and for probing the mechanism of channel gating.}, } @article {pmid30429322, year = {2018}, author = {Castaño, C and Kalko, S and Novials, A and Párrizas, M}, title = {Obesity-associated exosomal miRNAs modulate glucose and lipid metabolism in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12158-12163}, pmid = {30429322}, issn = {1091-6490}, abstract = {Obesity is frequently associated with metabolic disease. Here, we show that obesity changes the miRNA profile of plasma exosomes in mice, including increases in miR-122, miR-192, miR-27a-3p, and miR-27b-3p Importantly, treatment of lean mice with exosomes isolated from obese mice induces glucose intolerance and insulin resistance. Moreover, administration of control exosomes transfected with obesity-associated miRNA mimics strongly induces glucose intolerance in lean mice and results in central obesity and hepatic steatosis. Expression of the candidate target gene Ppara is decreased in white adipose tissue but not in the liver of mimic-treated (MIMIC) mice, and this is accompanied by increased circulating free fatty acids and hypertriglyceridemia. Treatment with a specific siRNA targeting Ppara transfected into exosomes recapitulates the phenotype induced by obesity-associated miRNAs. Importantly, simultaneously reducing free fatty acid plasma levels in MIMIC mice with either the lipolysis inhibitor acipimox or the PPARα agonist fenofibrate partially protects against these metabolic alterations. Overall, our data highlight the central role of obesity-associated exosomal miRNAs in the etiopathogeny of glucose intolerance and dyslipidemia.}, } @article {pmid30429321, year = {2018}, author = {Oishi, H and Takemura, H and Aoki, SC and Fujita, I and Amano, K}, title = {Microstructural properties of the vertical occipital fasciculus explain the variability in human stereoacuity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12289-12294}, pmid = {30429321}, issn = {1091-6490}, abstract = {Stereopsis is a fundamental visual function that has been studied extensively. However, it is not clear why depth discrimination (stereoacuity) varies more significantly among people than other modalities. Previous studies have reported the involvement of both dorsal and ventral visual areas in stereopsis, implying that not only neural computations in cortical areas but also the anatomical properties of white matter tracts connecting those areas can impact stereopsis. Here, we studied how human stereoacuity relates to white matter properties by combining psychophysics, diffusion MRI (dMRI), and quantitative MRI (qMRI). We performed a psychophysical experiment to measure stereoacuity and, in the same participants, we analyzed the microstructural properties of visual white matter tracts on the basis of two independent measurements, dMRI (fractional anisotropy, FA) and qMRI (macromolecular tissue volume; MTV). Microstructural properties along the right vertical occipital fasciculus (VOF), a major tract connecting dorsal and ventral visual areas, were highly correlated with measures of stereoacuity. This result was consistent for both FA and MTV, suggesting that the behavioral-structural relationship reflects differences in neural tissue density, rather than differences in the morphological configuration of fibers. fMRI confirmed that binocular disparity stimuli activated the dorsal and ventral visual regions near VOF endpoints. No other occipital tracts explained the variance in stereoacuity. In addition, the VOF properties were not associated with differences in performance on a different psychophysical task (contrast detection). These series of experiments suggest that stereoscopic depth discrimination performance is, at least in part, constrained by dorso-ventral communication through the VOF.}, } @article {pmid30429320, year = {2018}, author = {Hilbe, C and Schmid, L and Tkadlec, J and Chatterjee, K and Nowak, MA}, title = {Indirect reciprocity with private, noisy, and incomplete information.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12241-12246}, pmid = {30429320}, issn = {1091-6490}, abstract = {Indirect reciprocity is a mechanism for cooperation based on shared moral systems and individual reputations. It assumes that members of a community routinely observe and assess each other and that they use this information to decide who is good or bad, and who deserves cooperation. When information is transmitted publicly, such that all community members agree on each other's reputation, previous research has highlighted eight crucial moral systems. These "leading-eight" strategies can maintain cooperation and resist invasion by defectors. However, in real populations individuals often hold their own private views of others. Once two individuals disagree about their opinion of some third party, they may also see its subsequent actions in a different light. Their opinions may further diverge over time. Herein, we explore indirect reciprocity when information transmission is private and noisy. We find that in the presence of perception errors, most leading-eight strategies cease to be stable. Even if a leading-eight strategy evolves, cooperation rates may drop considerably when errors are common. Our research highlights the role of reliable information and synchronized reputations to maintain stable moral systems.}, } @article {pmid30429319, year = {2018}, author = {Sossin, WS}, title = {"Fragile" equilibrium between translation and transcription.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12086-12088}, pmid = {30429319}, issn = {1091-6490}, mesh = {Animals ; Cell Differentiation ; *Fragile X Mental Retardation Protein ; Fragile X Syndrome ; Mice ; *RNA, Messenger ; }, } @article {pmid30429318, year = {2018}, author = {Li, B and Dou, SX and Yuan, JW and Liu, YR and Li, W and Ye, F and Wang, PY and Li, H}, title = {Intracellular transport is accelerated in early apoptotic cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12118-12123}, pmid = {30429318}, issn = {1091-6490}, abstract = {Intracellular transport of cellular proteins and organelles is critical for establishing and maintaining intracellular organization and cell physiology. Apoptosis is a process of programmed cell death with dramatic changes in cell morphology and organization, during which signaling molecules are transported between different organelles within the cells. However, how the intracellular transport changes in cells undergoing apoptosis remains unknown. Here, we study the dynamics of intracellular transport by using the single-particle tracking method and find that both directed and diffusive motions of endocytic vesicles are accelerated in early apoptotic cells. With careful elimination of other factors involved in the intracellular transport, the reason for the acceleration is attributed to the elevation of adenosine triphosphate (ATP) concentration. More importantly, we show that the accelerated intracellular transport is critical for apoptosis, and apoptosis is delayed when the dynamics of intracellular transport is regulated back to the normal level. Our results demonstrate the important role of transport dynamics in apoptosis and shed light on the apoptosis mechanism from a physical perspective.}, } @article {pmid30429317, year = {2018}, author = {Plikus, MV and Andersen, B}, title = {Skin as a window to body-clock time.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12095-12097}, pmid = {30429317}, issn = {1091-6490}, support = {R01 AR067273/AR/NIAMS NIH HHS/United States ; R01 AR044882/AR/NIAMS NIH HHS/United States ; U01 AR073159/AR/NIAMS NIH HHS/United States ; R01 AR069653/AR/NIAMS NIH HHS/United States ; R01 AR056439/AR/NIAMS NIH HHS/United States ; R21 AR069962/AR/NIAMS NIH HHS/United States ; }, mesh = {Humans ; *Period Circadian Proteins ; *Skin ; }, } @article {pmid30429316, year = {2018}, author = {Karp, AT and Behrensmeyer, AK and Freeman, KH}, title = {Grassland fire ecology has roots in the late Miocene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12130-12135}, pmid = {30429316}, issn = {1091-6490}, abstract = {That fire facilitated the late Miocene C4 grassland expansion is widely suspected but poorly documented. Fire potentially tied global climate to this profound biosphere transition by serving as a regional-to-local driver of vegetation change. In modern environments, seasonal extremes in moisture amplify the occurrence of fire, disturbing forest ecosystems to create niche space for flammable grasses, which in turn provide fuel for frequent fires. On the Indian subcontinent, C4 expansion was accompanied by increased seasonal extremes in rainfall (evidenced by δ18Ocarbonate), which set the stage for fuel accumulation and fire-linked clearance during wet-to-dry seasonal transitions. Here, we test the role of fire directly by examining the abundance and distribution patterns of fire-derived polycyclic aromatic hydrocarbons (PAHs) and terrestrial vegetation signatures in n-alkane carbon isotopes from paleosol samples of the Siwalik Group (Pakistan). Two million years before the C4 grassland transition, fire-derived PAH concentrations increased as conifer vegetation declined, as indicated by a decrease in retene. This early increase in molecular fire signatures suggests a transition to more fire-prone vegetation such as a C3 grassland and/or dry deciduous woodland. Between 8.0 and 6.0 million years ago, fire, precipitation seasonality, and C4-grass dominance increased simultaneously (within resolution) as marked by sharp increases in fire-derived PAHs, δ18Ocarbonate, and 13C enrichment in n-alkanes diagnostic of C4 grasses. The strong association of evidence for fire occurrence, vegetation change, and landscape opening indicates that a dynamic fire-grassland feedback system was both a necessary precondition and a driver for grassland ecology during the first emergence of C4 grasslands.}, } @article {pmid30429315, year = {2018}, author = {Willis, IM and Moir, RD and Hernandez, N}, title = {Metabolic programming a lean phenotype by deregulation of RNA polymerase III.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12182-12187}, pmid = {30429315}, issn = {1091-6490}, support = {P30 CA013330/CA/NCI NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; P30 DK026687/DK/NIDDK NIH HHS/United States ; R01 GM120358/GM/NIGMS NIH HHS/United States ; }, abstract = {As a master negative regulator of RNA polymerase (Pol) III, Maf1 modulates transcription in response to nutrients and stress to balance the production of highly abundant tRNAs, 5S rRNA, and other small noncoding RNAs with cell growth and maintenance. This regulation of Pol III transcription is important for energetic economy as mice lacking Maf1 are lean and resist weight gain on normal and high fat diets. The lean phenotype of Maf1 knockout (KO) mice is attributed in part to metabolic inefficiencies which increase the demand for cellular energy and elevate catabolic processes, including autophagy/lipophagy and lipolysis. A futile RNA cycle involving increased synthesis and turnover of Pol III transcripts has been proposed as an important driver of these changes. Here, using targeted metabolomics, we find changes in the liver of fed and fasted Maf1 KO mice consistent with the function of mammalian Maf1 as a chronic Pol III repressor. Differences in long-chain acylcarnitine levels suggest that energy demand is higher in the fed state of Maf1 KO mice versus the fasted state. Quantitative metabolite profiling supports increased activity in the TCA cycle, the pentose phosphate pathway, and the urea cycle and reveals changes in nucleotide levels and the creatine system. Metabolite profiling also confirms key predictions of the futile RNA cycle hypothesis by identifying changes in many metabolites involved in nucleotide synthesis and turnover. Thus, constitutively high levels of Pol III transcription in Maf1 KO mice reprogram central metabolic pathways and waste metabolic energy through a futile RNA cycle.}, } @article {pmid30429314, year = {2018}, author = {Chin, AS and Worley, KE and Ray, P and Kaur, G and Fan, J and Wan, LQ}, title = {Epithelial Cell Chirality Revealed by Three-Dimensional Spontaneous Rotation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12188-12193}, pmid = {30429314}, issn = {1091-6490}, support = {DP2 HD083961/HD/NICHD NIH HHS/United States ; }, abstract = {Our understanding of the left-right (LR) asymmetry of embryonic development, in particular the contribution of intrinsic handedness of the cell or cell chirality, is limited due to the confounding systematic and environmental factors during morphogenesis and a ack of physiologically relevant in vitro 3D platforms. Here we report an efficient two-layered biomaterial platform for determining the chirality of individual cells, cell aggregates, and self-organized hollow epithelial spheroids. This bioengineered niche provides a uniform defined axis allowing for cells to rotate spontaneously with a directional bias toward either clockwise or counterclockwise directions. Mechanistic studies reveal an actin-dependent, cell-intrinsic property of 3D chirality that can be mediated by actin cross-linking via α-actinin-1. Our findings suggest that the gradient of extracellular matrix is an important biophysicochemical cue influencing cell polarity and chirality. Engineered biomaterial systems can serve as an effective platform for studying developmental asymmetry and screening for environmental factors causing birth defects.}, } @article {pmid30429313, year = {2018}, author = {Pineda, JJ and Miller, MA and Song, Y and Kuhn, H and Mikula, H and Tallapragada, N and Weissleder, R and Mitchison, TJ}, title = {Site occupancy calibration of taxane pharmacology in live cells and tissues.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11406-E11414}, pmid = {30429313}, issn = {1091-6490}, support = {K99 CA207744/CA/NCI NIH HHS/United States ; U01 CA206997/CA/NCI NIH HHS/United States ; F31 GM117882/GM/NIGMS NIH HHS/United States ; R01 GM039565/GM/NIGMS NIH HHS/United States ; R37 GM039565/GM/NIGMS NIH HHS/United States ; }, abstract = {Drug receptor site occupancy is a central pharmacology parameter that quantitatively relates the biochemistry of drug binding to the biology of drug action. Taxanes and epothilones bind to overlapping sites in microtubules (MTs) and stabilize them. They are used to treat cancer and are under investigation for neurodegeneration. In cells, they cause concentration-dependent inhibition of MT dynamics and perturbation of mitosis, but the degree of site occupancy required to trigger different effects has not been measured. We report a live cell assay for taxane-site occupancy, and relationships between site occupancy and biological effects across four drugs and two cell lines. By normalizing to site occupancy, we were able to quantitatively compare drug activities and cell sensitivities independent of differences in drug affinity and uptake/efflux kinetics. Across all drugs and cells tested, we found that inhibition of MT dynamics, postmitotic micronucleation, and mitotic arrest required successively higher site occupancy. We also found interesting differences between cells and drugs, for example, insensitivity of the spindle assembly checkpoint to site occupancy. By extending our assay to a mouse xenograft tumor model, we estimated the initial site occupancy required for paclitaxel to completely prevent tumor growth as 80%. The most important cellular action of taxanes for cancer treatment may be formation of micronuclei, which occurs over a broad range of site occupancies.}, } @article {pmid30429047, year = {2018}, author = {Conix, S}, title = {Radical pluralism, classificatory norms and the legitimacy of species classifications.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.shpsc.2018.11.002}, pmid = {30429047}, issn = {1879-2499}, abstract = {Moderate pluralism is a popular position in contemporary philosophy of biology. Despite its popularity, various authors have argued that it tends to slide off into a radical form of pluralism that is both normatively and descriptively unacceptable. This paper looks at the case of biological species classification, and evaluates a popular way of avoiding radical pluralism by relying on the shared aims and norms of a discipline. The main contention is that while these aims and norms may play an important role in the legitimacy of species classifications, they fail to fend off radical pluralism. It follows from this that the legitimacy of species classifications is also determined by local decisions about the aims of research and how to operationalize and balance these. This is important, I argue, because it means that any acceptable view on the legitimacy of classification should be able to account for these local decisions.}, } @article {pmid30428919, year = {2018}, author = {Darré, T and Saka, B and Walla, A and Ekouévi, KD and Folligan, K}, title = {Sexuality, sexually transmitted infections and contraception among health sciences students in university of Lomé, Togo.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {808}, pmid = {30428919}, issn = {1756-0500}, abstract = {OBJECTIVES: Evaluate the practice of sexuality, contraception and the risk of sexually transmitted infections among students in the Faculty of Health Sciences, University of Lomé, Togo.

RESULTS: Three hundred and sixteen (316) students were interviewed, with a response rate of 43.3%. The average age of students completing the form was 21.4 ± 2.7 years and their sex ratio was 2.2. Of this number of students who completed the form, 51.8% have already had sex. The mean age of first intercourse was 17.9 ± 3.2 years; 70.3% were heterosexual. Regarding the number of sexual partners, 48.5% of students had more than one partner, of whom 15.9% had at least 5 sexual partners. 21.5% of these students had only one sexual intercourse per month. Regarding contraception among students with the card, 67.5% of students used a method of contraception. Among those using contraceptives, it was a 55.3% condom, followed by the Ogino method at 14.1%. Some of our respondents used more than one method of contraception and 28.5% of respondents indicated that their partners used a method of contraception. For STIs, 10.8% of students completing the form were already infected. Gonorrhea was reported in 30.4% of cases, candidiasis in 26.1% of cases.}, } @article {pmid30428917, year = {2018}, author = {Aguilar-Luis, MA and Palacios-Cuervo, F and Espinal-Reyes, F and Calderón-Rivera, A and Levy-Blitchtein, S and Palomares-Reyes, C and Silva-Caso, W and Zavaleta-Gavidia, V and Bazán-Mayra, J and Cornejo-Tapia, A and Del Valle-Mendoza, J and Del Valle, LJ}, title = {Highly clarithromycin-resistant Helicobacter pylori infection in asymptomatic children from a rural community of Cajamarca-Peru.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {809}, pmid = {30428917}, issn = {1756-0500}, support = {Grant:UPC-EXP 004-2016. Lima-Peru.//4th Incentive for Research of the Universidad Peruana de Ciencias Aplicadas./ ; }, abstract = {OBJECTIVE: The objective of this study was to determine the prevalence of clarithromycin-resistant Helicobacter pylori in asymptomatic children in a rural community of Cajamarca (northern Peru).

RESULTS: Helicobacter pylori was detected in 17.2% (49/285) of the samples. Unboiled water consumption the most frequent associated factor in patients with positive PCR for H. pylori infection (93.9%). Clarithromycin resistant mutations were found in 79.6% (39/49) of the positive samples for H. pylori. The most frequent mutation was A2142G (46.9%), followed by the double-mutation A2142G-A2143G (28.6%).}, } @article {pmid30428904, year = {2018}, author = {Arteaga-Tlecuitl, R and Sanchez-Sandoval, AL and Ramirez-Cordero, BE and Rosendo-Pineda, MJ and Vaca, L and Gomora, JC}, title = {Increase of CaV3 channel activity induced by HVA β1b-subunit is not mediated by a physical interaction.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {810}, pmid = {30428904}, issn = {1756-0500}, support = {167790//Consejo Nacional de Ciencia y Tecnología/ ; IN206917//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, abstract = {OBJECTIVE: Low voltage-activated (LVA) calcium channels are crucial for regulating oscillatory behavior in several types of neurons and other excitable cells. LVA channels dysfunction has been implicated in epilepsy, neuropathic pain, cancer, among other diseases. Unlike for High Voltage-Activated (HVA) channels, voltage-dependence and kinetics of currents carried by recombinant LVA, i.e., CaV3 channels, are quite similar to those observed in native currents. Therefore, whether these channels are regulated by HVA auxiliary subunits, remain controversial. Here, we used the α1-subunits of CaV3.1, CaV3.2, and CaV3.3 channels, together with HVA auxiliary β-subunits to perform electrophysiological, confocal microscopy and immunoprecipitation experiments, in order to further explore this possibility.

RESULTS: Functional expression of CaV3 channels is up-regulated by all four β-subunits, although most consistent effects were observed with the β1b-subunit. The biophysical properties of CaV3 channels were not modified by any β-subunit. Furthermore, although β1b-subunits increased colocalization of GFP-tagged CaV3 channels and the plasma membrane of HEK-293 cells, western blots analysis revealed the absence of physical interaction between CaV3.3 and β1b-subunits as no co-immunoprecipitation was observed. These results provide solid evidence that the up-regulation of LVA channels in the presence of HVA-β1b subunit is not mediated by a high affinity interaction between both proteins.}, } @article {pmid30428854, year = {2018}, author = {García-Angulo, A and Merlo, MA and Portela-Bens, S and Rodríguez, ME and García, E and Al-Rikabi, A and Liehr, T and Rebordinos, L}, title = {Evidence for a Robertsonian fusion in Solea senegalensis (Kaup, 1858) revealed by zoo-FISH and comparative genome analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {818}, pmid = {30428854}, issn = {1471-2164}, support = {AGL2014-51860-C2-1-P//Spanish Ministerio de Ciencia e Innovación-FEDER/ ; }, abstract = {BACKGROUND: Solea senegalensis (Kaup, 1858) is a commercially important flatfish species, belonging to the Pleuronectiformes order. The taxonomy of this group has long been controversial, and the karyotype of the order presents a high degree of variability in diploid number, derived from chromosomal rearrangements such as Robertsonian fusions. Previously it has been proposed that the large metacentric chromosome of S. senegalensis arises from this kind of chromosome rearrangement and that this is a proto-sex chromosome.

RESULTS: In this work, the Robertsonian origin of the large metacentric chromosome of S. senegalensis has been tested by the Zoo-FISH technique applied to two species of the Soleidae family (Dicologlossa cuneata and Dagetichthys lusitanica), and by comparative genome analysis with Cynoglossus semilaevis. From the karyotypic analysis we were able to determine a chromosome complement comprising 2n = 50 (FN = 54) in D. cuneata and 2n = 42 (FN = 50) in D. lusitanica. The large metacentric painting probe gave consistent signals in four acrocentric chromosomes of the two Soleidae species; and the genome analysis proved a common origin with four chromosome pairs of C. semilaevis. As a result of the genomic analysis, up to 61 genes were annotated within the thirteen Bacterial Artificial Chromosome clones analysed.

CONCLUSIONS: These results confirm that the large metacentric chromosome of S. senegalensis originated from a Robertsonian fusion and provide new data about the chromosome evolution of S. senegalensis in particular, and of Pleuronectiformes in general.}, } @article {pmid30428853, year = {2018}, author = {Baccarella, A and Williams, CR and Parrish, JZ and Kim, CC}, title = {Empirical assessment of the impact of sample number and read depth on RNA-Seq analysis workflow performance.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {423}, pmid = {30428853}, issn = {1471-2105}, support = {R01 NS076614//National Institute of Neurological Disorders and Stroke/ ; U19 AI089674//National Institute of Allergy and Infectious Diseases/ ; Research Innovation Award//University of Washington/ ; P30 DK063720//National Institute of Diabetes and Digestive and Kidney Diseases/ ; P30 AI027763//University of California, San Francisco, Center for AIDS Research/ ; Community Health Foundation Summer Scholarship//ACCMA/ ; R21 AI114916//National Institute of Allergy and Infectious Diseases/ ; U10 EY008057//National Eye Institute/ ; DGE1256032//National Science Foundation (US)/ ; F31- NS106775-01//National Institute of Neurological Disorders and Stroke/ ; F31 NS106775/NS/NINDS NIH HHS/United States ; }, mesh = {Gene Expression Profiling/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; RNA/*genetics ; Sequence Analysis, RNA/*methods ; *Workflow ; }, abstract = {BACKGROUND: RNA-Sequencing analysis methods are rapidly evolving, and the tool choice for each step of one common workflow, differential expression analysis, which includes read alignment, expression modeling, and differentially expressed gene identification, has a dramatic impact on performance characteristics. Although a number of workflows are emerging as high performers that are robust to diverse input types, the relative performance characteristics of these workflows when either read depth or sample number is limited-a common occurrence in real-world practice-remain unexplored.

RESULTS: Here, we evaluate the impact of varying read depth and sample number on the performance of differential gene expression identification workflows, as measured by precision, or the fraction of genes correctly identified as differentially expressed, and by recall, or the fraction of differentially expressed genes identified. We focus our analysis on 30 high-performing workflows, systematically varying the read depth and number of biological replicates of patient monocyte samples provided as input. We find that, in general for most workflows, read depth has little effect on workflow performance when held above two million reads per sample, with reduced workflow performance below this threshold. The greatest impact of decreased sample number is seen below seven samples per group, when more heterogeneity in workflow performance is observed. The choice of differential expression identification tool, in particular, has a large impact on the response to limited inputs.

CONCLUSIONS: Among the tested workflows, the recall/precision balance remains relatively stable at a range of read depths and sample numbers, although some workflows are more sensitive to input restriction. At ranges typically recommended for biological studies, performance is more greatly impacted by the number of biological replicates than by read depth. Caution should be used when selecting analysis workflows and interpreting results from low sample number experiments, as all workflows exhibit poorer performance at lower sample numbers near typically reported values, with variable impact on recall versus precision. These analyses highlight the performance characteristics of common differential gene expression workflows at varying read depths and sample numbers, and provide empirical guidance in experimental and analytical design.}, } @article {pmid30428844, year = {2018}, author = {Ta, KN and Khong, NG and Ha, TL and Nguyen, DT and Mai, DC and Hoang, TG and Phung, TPN and Bourrie, I and Courtois, B and Tran, TTH and Dinh, BY and LA, TN and DO, NV and Lebrun, M and Gantet, P and Jouannic, S}, title = {A genome-wide association study using a Vietnamese landrace panel of rice (Oryza sativa) reveals new QTLs controlling panicle morphological traits.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {282}, pmid = {30428844}, issn = {1471-2229}, support = {106-NN.02-2016.60//Nafosted/ ; EVOREPRICE 1201-004//Agropolis Fondation/ ; }, mesh = {Flowers/anatomy & histology/genetics/growth & development ; *Genome-Wide Association Study ; Genotyping Techniques ; Meristem/anatomy & histology/genetics/growth & development ; Oryza/anatomy & histology/*genetics/growth & development ; Phenotype ; Plant Breeding ; Quantitative Trait Loci/*genetics ; }, abstract = {CONTEXT: Yield improvement is an important issue for rice breeding. Panicle architecture is one of the key components of rice yield and exhibits a large diversity. To identify the morphological and genetic determinants of panicle architecture, we performed a detailed phenotypic analysis and a genome-wide association study (GWAS) using an original panel of Vietnamese landraces.

RESULTS: Using a newly developed image analysis tool, morphological traits of the panicles were scored over two years: rachis length; primary, secondary and tertiary branch number; average length of primary and secondary branches; average length of internode on rachis and primary branch. We observed a high contribution of spikelet number and secondary branch number per panicle to the overall phenotypic diversity in the dataset. Twenty-nine stable QTLs associated with seven traits were detected through GWAS over the two years. Some of these QTLs were associated with genes already implicated in panicle development. Importantly, the present study revealed the existence of new QTLs associated with the spikelet number, secondary branch number and primary branch number traits.

CONCLUSIONS: Our phenotypic analysis of panicle architecture variation suggests that with the panel of samples used, morphological diversity depends largely on the balance between indeterminate vs. determinate axillary meristem fate on primary branches, supporting the notion of differences in axillary meristem fate between rachis and primary branches. Our genome-wide association study led to the identification of numerous genomic sites covering all the traits studied and will be of interest for breeding programs aimed at improving yield. The new QTLs detected in this study provide a basis for the identification of new genes controlling panicle development and yield in rice.}, } @article {pmid30428842, year = {2018}, author = {Huang, X and Cheng, X and Sun, P and Tang, C and Ni, F and Liu, G}, title = {Characteristics of NDM-1-producing Klebsiella pneumoniae ST234 and ST1412 isolates spread in a neonatal unit.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {186}, pmid = {30428842}, issn = {1471-2180}, support = {ZDXKB2016005//the Project of the Key Laboratory for Laboratory Medicine of Jiangsu Province/ ; SJLX15_0436//the innovation project for postgraduate education of Jiangsu Province/ ; }, abstract = {BACKGROUND: The emergence of carbapenem-resistant Klebsiella pneumoniae (CR-KP) has become a significant problem worldwide and also being a major threat to children and newborns. Here we report an outbreak of NDM-1-producing K. pneumoniae in a neonatal unit.

RESULTS: Six CR-KP strains, isolated from neonates with symptoms of infection, were identified using a VITEK-2 compact system, and the clinical data were retrieved from the electronic case records. In vitro susceptibility testing with broth dilution method showed that all six K. pneumoniae isolates were resistant to carbapenems and susceptible to colistin, aminoglycosides, fluoroquinolones and tigecycline. Based on the polymerase chain reaction results, each isolate was found to be blaNDM-1 gene positive. Clonal relationships were analysed using pulsed-field gel electrophoresis (PFGE) and multilocus sequence typing (MLST) and showed that two different PFGE patterns were formed, which belonged to sequence types ST234 and ST1412. Plasmids carrying blaNDM-1 were successfully transferred from four of the six isolates to an Escherichia coli recipient through conjugative assays. S1-PFGE and Southern blot hybridization showed that four NDM-1-producing K. pneumoniae were clonal and carried blaNDM-1 on the same plasmid. The outbreak was effectively controlled by reducing the potential infection sources. All the patients were successfully treated and recovered after receiving an increased dose of carbapenems. Although the source of this outbreak was not clear, comprehensive measures were carried out and the outbreak was effectively controlled.

CONCLUSIONS: ST234 and ST1412 of NDM-1-producing Klebsiella pneumoniae are the resistant clone spread in the neonatal unit, comprehensive infection control measures and optimized carbapenem therapy played an important role in controlling this NDM-1-producing K. pneumoniae outbreak.}, } @article {pmid30428831, year = {2018}, author = {Kolberg, L and Kuzmin, I and Adler, P and Vilo, J and Peterson, H}, title = {funcExplorer: a tool for fast data-driven functional characterisation of high-throughput expression data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {817}, pmid = {30428831}, issn = {1471-2164}, support = {PSG59//Eesti Teadusagentuur/ ; IUT34-4//Eesti Teadusagentuur (EE)/ ; EXCITE//European Regional Development Fund/ ; No 2014-2020.4.01.16-0271, ELIXIR)//European Union through the Structural Fund/ ; }, abstract = {BACKGROUND: A widely applied approach to extract knowledge from high-throughput genomic data is clustering of gene expression profiles followed by functional enrichment analysis. This type of analysis, when done manually, is highly subjective and has limited reproducibility. Moreover, this pipeline can be very time-consuming and resource-demanding as enrichment analysis is done for tens to hundreds of clusters at a time. Thus, the task often needs programming skills to form a pipeline of different software tools or R packages to enable an automated approach. Furthermore, visualising the results can be challenging.

RESULTS: We developed a web tool, funcExplorer, which automatically combines hierarchical clustering and enrichment analysis to detect functionally related gene clusters. The functional characterisation is achieved using structured knowledge from data sources such as Gene Ontology, KEGG and Reactome pathways, Human Protein Atlas, and Human Phenotype Ontology. funcExplorer includes various measures for finding biologically meaningful clusters, provides a modern graphical user interface, and has wide-ranging data export and sharing options as well as software transparency by open-source code. The results are presented in a visually compact and interactive format, enabling users to explore the biological essence of the data. We compared our results with previously published gene clusters to demonstrate that funcExplorer can perform the data characterisation equally well, but without requiring labour-intensive manual interference.

CONCLUSIONS: The open-source web tool funcExplorer enables scientists with high-throughput genomic data to obtain a preliminary interactive overview of the expression patterns, gene names, and shared functionalities in their dataset in a visually pleasing format. funcExplorer is publicly available at https://biit.cs.ut.ee/funcexplorer.}, } @article {pmid30428830, year = {2018}, author = {Choo-Wosoba, H and Albert, PS and Zhu, B}, title = {hsegHMM: hidden Markov model-based allele-specific copy number alteration analysis accounting for hypersegmentation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {424}, pmid = {30428830}, issn = {1471-2105}, mesh = {*Alleles ; DNA Copy Number Variations/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Somatic copy number alternation (SCNA) is a common feature of the cancer genome and is associated with cancer etiology and prognosis. The allele-specific SCNA analysis of a tumor sample aims to identify the allele-specific copy numbers of both alleles, adjusting for the ploidy and the tumor purity. Next generation sequencing platforms produce abundant read counts at the base-pair resolution across the exome or whole genome which is susceptible to hypersegmentation, a phenomenon where numerous regions with very short length are falsely identified as SCNA.

RESULTS: We propose hsegHMM, a hidden Markov model approach that accounts for hypersegmentation for allele-specific SCNA analysis. hsegHMM provides statistical inference of copy number profiles by using an efficient E-M algorithm procedure. Through simulation and application studies, we found that hsegHMM handles hypersegmentation effectively with a t-distribution as a part of the emission probability distribution structure and a carefully defined state space. We also compared hsegHMM with FACETS which is a current method for allele-specific SCNA analysis. For the application, we use a renal cell carcinoma sample from The Cancer Genome Atlas (TCGA) study.

CONCLUSIONS: We demonstrate the robustness of hsegHMM to hypersegmentation. Furthermore, hsegHMM provides the quantification of uncertainty in identifying allele-specific SCNAs over the entire chromosomes. hsegHMM performs better than FACETS when read depth (coverage) is uneven across the genome.}, } @article {pmid30428829, year = {2018}, author = {Baig, MA and Ahmad, J and Bagheri, R and Ali, AA and Al-Huqail, AA and Ibrahim, MM and Qureshi, MI}, title = {Proteomic and ecophysiological responses of soybean (Glycine max L.) root nodules to Pb and hg stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {283}, pmid = {30428829}, issn = {1471-2229}, support = {RGP231//Deanship of Scientific Research, King Saud University, Riyadh (SA)/ ; }, mesh = {Antioxidants/metabolism ; Ascorbate Peroxidases/metabolism ; Catalase/metabolism ; Glutathione Transferase/metabolism ; Lead/*toxicity ; Mercury/*toxicity ; Oxidative Stress ; Plant Leaves/anatomy & histology/drug effects/genetics/physiology ; Plant Proteins/metabolism ; *Proteomics ; Root Nodules, Plant/anatomy & histology/drug effects/genetics/physiology ; Soybeans/anatomy & histology/drug effects/genetics/*physiology ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Lead (Pb) and mercury (Hg) are persistent hazardous metals in industrially polluted soils which can be toxic in low quantities. Metal toxicity can cause changes at cellular and molecular level which should be studied for better understanding of tolerance mechanism in plants. Soybean (Glycine max L.) is an important oilseed crop of the world including India. Indian soils growing soybean are often contaminated by Pb and Hg. The aim of this study was to explore how soybean root nodule responds to Pb and Hg through proteomic and ecophysiological alterations in order to enhance tolerance to metal stress.

RESULTS: Soybean plants were exposed to Pb (30 ppm PbCl2) and Hg (0.5 ppm HgCl2) to study histological, histochemical, biochemical and molecular response of N2-fixing symbiotic nodules. Both Pb and Hg treatment increased the level of oxidative stress in leaves and nodules. Chlorosis in leaves and morphological/anatomical changes in nodules were observed. Activities of ascorbate peroxidase, glutathione reductase and catalase were also modulated. Significant changes were observed in abundance of 76 proteins by Pb and Hg. Pb and Hg influenced abundance of 33 proteins (17 up and 16 down) and 43 proteins (33 up and 10 down), respectively. MS/MS ion search identified 55 proteins which were functionally associated with numerous cellular functions. Six crucial proteins namely catalase (CAT), allene oxide synthase (AOS), glutathione S-transferase (GST), calcineurin B like (CBL), calmodulin like (CML) and rapid alkalinisation factor (RAF) were selected for transcript abundance estimation. The qRT-PCR based real time expression exhibited a positive correlation with proteomics expression except for GST and RAF.

CONCLUSION: Soybean root nodule responds to metal stress by increased abundance of defence, development and repair related proteins. An efficient proteomic modulation might lead to metal-induced stress tolerance in N2-fixing nodules. Although concentrations of Pb and Hg used in the study cannot be considered equimolar, yet Hg seems to induce more changes in nodule proteomic profile, and higher damage to both bacteroides and root anatomy.}, } @article {pmid30428828, year = {2018}, author = {Mutai, WC and Muigai, AWT and Waiyaki, P and Kariuki, S}, title = {Multi-drug resistant Salmonella enterica serovar Typhi isolates with reduced susceptibility to ciprofloxacin in Kenya.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {187}, pmid = {30428828}, issn = {1471-2180}, abstract = {BACKGROUND: Typhoid fever remains a public health concern in developing countries especially among the poor who live in informal settlements devoid of proper sanitation and clean water supply. In addition antimicrobial resistance poses a major challenge in management of the disease. This study assessed the antimicrobial susceptibility patterns of Salmonella enterica serotype Typhi (S. Typhi) isolated from typhoid fever cases (2004-2007).

METHODS: A cross sectional study was conducted on 144 archived S. Typhi isolates (2004-2007) tested against 11 antimicrobial agents by quality controlled disk diffusion technique. Isolates resistant to ampicillin, chloramphenicol, and cotrimoxazole were considered Multidrug resistant (MDR). Thirty MDR isolates were selected randomly and further tested using minimum inhibitory concentration (MIC) E-test.

RESULTS: Sixteen percent (23/144) of the isolates were susceptible to all the antibiotics tested while 68% were resistant to three or more of the 11 antibiotics tested. The isolates showed a high susceptibility to ceftriaxone (94%) and gentamicin (97%). A high percentage of resistance was observed for the conventional first-line antibiotics; ampicillin (72%), chloramphenicol (72%), and cotrimoxazole (70%). Sixty-nine percent of the isolates (100/144) showed reduced susceptibility to ciprofloxacin. All the 30 (100%) isolates selected for MIC test were susceptible to amoxicillin-clavulanic acid. All except one of the 30 isolates were susceptible to ceftriaxone while majority 21 (70%) recorded an intermediate susceptibility to ciprofloxacin with MIC of 0.12-0.5 μg/mL.

CONCLUSION: A large proportion of S. Typhi isolates were MDR and also showed reduced susceptibility to ciprofloxacin. Fluoroquinolone resistance is emerging and this may pose a challenge in treatment of typhoid in future. There is need for routine surveillance to monitor this phenotype in clinical settings.}, } @article {pmid30428700, year = {2018}, author = {March, E and Van Doorn, G and Grieve, R}, title = {Netflix and Chill? What Sex Differences Can Tell Us About Mate Preferences in (Hypothetical) Booty-Call Relationships.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918812138}, doi = {10.1177/1474704918812138}, pmid = {30428700}, issn = {1474-7049}, abstract = {The booty-call relationship is defined by both sexual characteristics and emotional involvement. In the current study, men's and women's preferences for a booty-call mate were explored. Men and women were predicted to exhibit different mate preferences depending on whether they considered a booty-call relationship a short- or long-term relationship. Participants (N = 559, 74% women) completed an anonymous online questionnaire, designing their ideal booty-call mate using the mate dollars paradigm. Both sexes considered the physical attractiveness and kindness of a booty-call mate a necessity, expressing both short- and long-term mate preferences. The current study highlights the need to explore mate preferences outside the dichotomy of short- and long-term relationships, providing evidence of a compromise relationship.}, } @article {pmid30428072, year = {2018}, author = {Teufel, AI and Johnson, MM and Laurent, JM and Kachroo, AH and Marcotte, EM and Wilke, CO}, title = {The many nuanced evolutionary consequences of duplicated genes.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy210}, pmid = {30428072}, issn = {1537-1719}, support = {DP1 GM106408/GM/NIGMS NIH HHS/United States ; R35 GM122480/GM/NIGMS NIH HHS/United States ; }, abstract = {Gene duplication is seen as a major source of structural and functional divergence in genome evolution. Under the conventional models of sub- or neofunctionalizaton, functional changes arise in one of the duplicates after duplication. However, we suggest here that the presence of a duplicated gene can result in functional changes to its interacting partners. We explore this hypothesis by in-silico evolution of a heterodimer when one member of the interacting pair is duplicated. We examine how a range of selection pressures and protein structures leads to differential patterns of evolutionary divergence. We find that a surprising number of distinct evolutionary trajectories can be observed even in a simple three member system. Further, we observe that selection to correct dosage imbalance can affect the evolution of the initial function in several unexpected ways. For example, if a duplicate is under selective pressure to avoid binding its original binding partner, this can lead to changes in the binding interface of a non-duplicated interacting partner to exclude the duplicate. Hence, independent of the fate of the duplicate, its presence can impact how the original function operates. Additionally, we introduce a conceptual framework to describe how interacting partners cope with dosage imbalance after duplication. Contextualizing our results within this framework reveals that the evolutionary path taken by a duplicate's interacting partners is highly stochastic in nature. Consequently, the fate of duplicate genes may not only be controlled by their own ability to accumulate mutations but also by how interacting partners cope with them.}, } @article {pmid30428071, year = {2018}, author = {Hallmark, B and Karafet, TM and Hsieh, P and Osipova, LP and Watkins, JC and Hammer, MF}, title = {Genomic Evidence of Local Adaptation to Climate and Diet in Indigenous Siberians.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy211}, pmid = {30428071}, issn = {1537-1719}, abstract = {The indigenous inhabitants of Siberia live in some of the harshest environments on earth, experiencing extended periods of severe cold temperatures, dramatic variation in photoperiod, and limited and highly variable food resources. While the successful long-term settlement of this area by humans required multiple behavioral and cultural innovations, the nature of the underlying genetic changes has generally remained elusive. In this study, we used a three-part approach to identify putative targets of positive natural selection in Siberians. We first performed selection scans on whole exome and genome-wide SNP array data from multiple Siberian populations. We then annotated candidates in the tails of the empirical distributions, focusing on candidates with evidence linking them to biological processes and phenotypes previously identified as relevant to adaptation in circumpolar groups. The top candidates were then genotyped in additional populations to determine their spatial allele frequency distributions and associations with climate variables. Our analysis reveals missense mutations in three genes involved in lipid metabolism (PLA2G2A, PLIN1, ANGPTL8) that exhibit genomic and spatial patterns consistent with selection for cold climate and/or diet. These variants are unified by their connection to brown adipose tissue, and may help to explain previously observed physiological differences in Siberians such as low serum lipid levels and increased basal metabolic rate. These results support the hypothesis that indigenous Siberians have genetically adapted to their local environment by selection on multiple genes.}, } @article {pmid30428070, year = {2018}, author = {Zeng, K and Jackson, BC}, title = {Methods for estimating demography and detecting between-locus differences in the effective population size and mutation rate.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy212}, pmid = {30428070}, issn = {1537-1719}, abstract = {It is known that the effective population size (Ne) and the mutation rate (u) vary across the genome. Here we show that ignoring this heterogeneity may lead to biased estimates of past demography. To solve the problem, we develop new methods for jointly inferring past changes in population size and detecting variation in Ne and u between loci. These methods rely on either polymorphism data alone or both polymorphism and divergence data. In addition to inferring demography, we can use the methods to study a variety of questions: (1) comparing sex chromosomes to autosomes (for finding evidence for male-driven evolution, an unequal sex ratio, or sex-biased demographic changes); (2) analysing multi-locus data from within autosomes or sex chromosomes (for studying determinants of variability in Ne and u). Simulations suggest that the methods can provide accurate parameter estimates and have substantial statistical power for detecting difference in Ne and u. As an example, we use the methods to analyse a polymorphism dataset from Drosophila simulans. We find clear evidence for rapid population expansion. The results also indicate that the autosomes have a higher mutation rate than the X chromosome, and that the sex ratio is probably female-biased. The new methods have been implemented in a user-friendly package.}, } @article {pmid30427304, year = {2019}, author = {MacFadyen, AC and Drigo, I and Harrison, EM and Parkhill, J and Holmes, MA and Paterson, GK}, title = {Staphylococcus caeli sp. nov., isolated from air sampling in an industrial rabbit holding.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {82-86}, doi = {10.1099/ijsem.0.003098}, pmid = {30427304}, issn = {1466-5034}, abstract = {Strain 82T, a Gram-stain-positive, coagulase-negative staphylococcus was isolated from an air sample obtained from an industrial rabbit holding in Italy. It is phylogenetically closely related to the coagulase-negative species Staphylococcus saprophyticus, Staphylococcus xylosus and Staphylococcus edaphicus. However, it could be distinguished from these species by sequence differences between the 16S rRNA, hsp60, rpoB, dnaJ and gap genes. At the whole genome level, the isolate had an average nucleotide identity of <95 % and an inferred DNA-DNA hybridization of <70 % when compared to these species. Based on the genotypic results, it is proposed that this isolate is a novel species, with the name Staphylococcus caeli sp. nov. The type strain is 82BT (=NCTC 14063T=CCUG 71912T).}, } @article {pmid30427302, year = {2019}, author = {Xi, ZW and Huang, LN and Li, Y and Hui, FL}, title = {Vanrija jinghongensis sp. nov., an asexual basidiomycetous yeast from rotting wood.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {105-108}, doi = {10.1099/ijsem.0.003108}, pmid = {30427302}, issn = {1466-5034}, abstract = {Three strains of a novel basidiomycetous yeast were isolated from the Xishuangbanna Tropical Rainforest, Yunnan Province, PR China. Sequence analysis of the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) regions indicated that the novel species represents a member of the genus Vanrija. It differed from the most closely related known species, Vanrija albida CBS 2839T, by 1.5 % sequence divergence (seven substitutions and two gaps out of 597 bp) in the D1/D2 domains and by 7.4 % sequence divergence (17 substitutions and 20 gaps over 495 bp) in the ITS regions, respectively. The three strains of the novel species reproduced asexually, and no mating could be found. In contrast to V. albida, the novel yeast species was able to assimilate d-glucosamine, inulin, erythritol and galactitol and unable to assimilate raffinose. The name Vanrija jinghongensis sp. nov. is proposed to accommodate these strains, with NYNU 17910T (=CICC 33269=CBS 15229) as the type strain.}, } @article {pmid30427301, year = {2019}, author = {Li, L and Wang, J and Zhou, YJ and Lin, HW and Lu, YH}, title = {Streptomyces reniochalinae sp. nov. and Streptomyces diacarni sp. nov., from marine sponges.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {99-104}, doi = {10.1099/ijsem.0.003109}, pmid = {30427301}, issn = {1466-5034}, abstract = {Two marine actinomycete strains, LHW50302T and LHW51701T, were isolated from marine sponges collected in Sansha, Hainan Province, China. The morphological, chemotaxonomic and phylogenetic characteristics were consistent with their classification in the genus Streptomyces. The strains formed hooked and looped chains of arthrospores with smooth surfaces. The cell-wall hydrolysates of the strains contained ll-diaminopimelic acid as the diagnostic diamino acid. MK-9(H8) was the predominant menaquinone. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylinositol. Major fatty acids of the strains were iso-C16 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The 16S rRNA gene sequences indicated that the strains clustered together with Streptomyces albus CGMCC 4.1640T and Streptomyces qinglanensis CGMCC 4.6825T. Multilocus sequence analysis (MLSA) confirmed their relationship. Genome relatedness in forms of average nucleotide identity, digital DNA-DNA hybridization value and MLSA evolutionary distance between each of the strains and its closest relatives showed that they belonged to distinct species. On the basis of these results, strains LHW50302T and LHW51701T belong to two novel species in the genus Streptomyces, for which the names Streptomyces reniochalinae sp. nov. (type strain LHW50302T=CCTCC AA 2018013T=DSM 106194T) and Streptomyces diacarni sp. nov. (type strain LHW51701T=CCTCC AA 2018017T=DSM 106126T) are proposed, respectively.}, } @article {pmid30426469, year = {2018}, author = {Betancur-R, R and Arcila, D and Vari, RP and Hughes, LC and Oliveira, C and Sabaj, MH and Ortí, G}, title = {Phylogenomic incongruence, hypothesis testing, and taxonomic sampling: The monophyly of characiform fishes.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13649}, pmid = {30426469}, issn = {1558-5646}, support = {P20GM103475//INBRE/ ; //National Institute of General Medical Sciences/ ; //National Institutes of Health/ ; DEB-147184//National Science Foundation/ ; DEB-1541491//National Science Foundation/ ; DEB-1257813//National Science Foundation/ ; DEB-1457426//National Science Foundation/ ; DEB-1541554//National Science Foundation/ ; 306054/2006-0//CNPq/ ; 2014/26508-3//FAPESP/ ; }, abstract = {Phylogenomic studies using genome-wide datasets are quickly becoming the state of the art for systematics and comparative studies, but in many cases, they result in strongly supported incongruent results. The extent to which this conflict is real depends on different sources of error potentially affecting big datasets (assembly, stochastic, and systematic error). Here, we apply a recently developed methodology (GGI or gene genealogy interrogation) and data curation to new and published datasets with more than 1000 exons, 500 ultraconserved element (UCE) loci, and transcriptomic sequences that support incongruent hypotheses. The contentious non-monophyly of the order Characiformes proposed by two studies is shown to be a spurious outcome induced by sample contamination in the transcriptomic dataset and an ambiguous result due to poor taxonomic sampling in the UCE dataset. By exploring the effects of number of taxa and loci used for analysis, we show that the power of GGI to discriminate among competing hypotheses is diminished by limited taxonomic sampling, but not equally sensitive to gene sampling. Taken together, our results reinforce the notion that merely increasing the number of genetic loci for a few representative taxa is not a robust strategy to advance phylogenetic knowledge of recalcitrant groups. We leverage the expanded exon capture dataset generated here for Characiformes (206 species in 23 out of 24 families) to produce a comprehensive phylogeny and a revised classification of the order.}, } @article {pmid30426159, year = {2018}, author = {Mohanty, I and Rath, A and Swain, SP and Pradhan, N and Hazra, RK}, title = {Wolbachia Population in Vectors and Non-vectors: A Sustainable Approach Towards Dengue Control.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1596-8}, pmid = {30426159}, issn = {1432-0991}, support = {0//Lady Tata Memorial Trust/ ; }, abstract = {Wolbachia is gram negative obligate endosymbiont known for reproductive manipulation in the host. It is important to study the presence of natural Wolbachia in mosquitoes which can later help in understanding the effect of transfected strain on indigenous strain. With this view, the present study is undertaken to focus on the prevalence, diversity, infection frequencies, phylogeny and density of indigenous Wolbachia strains in wild mosquito species of Odisha. Our study confirms Wolbachia presence in Ae. albopictus, Cx. quinquefasciatus, Cx. vishnui, Cx. gelidus, Ar. subalbatus, Mn. uniformis, and Mn. indiana. Wolbachia in the above mosquitoes were separated into two supergroups (A and B). Ae. albopictus, the major vector of dengue and chikungungunya had both super-infection and mono-infection. The ovaries of Ae. albopictus were highest in density of Wolbachia as compared to midguts or salivary glands. wAlBA and wAlbB density were variable in mosquitoes of F1 generation for both the sex and at different age. We also found that Wolbachia super-infection in females tends to increase whereas wAlbA density reduced completely as compared to wAlbB in males when they grew old. Giemsa stained squashed ovaries revealed pink pleomorphic Wolbachia cells with different shapes and forms. This study is unique in its kind covering the major aspects of the endosymbiont Wolbachia and focusing on its potential as a biocontrol agent in arboviral outbreaks. Knowledge on potential of the indigenous strain and interactions between Wolbachia and viruses can be utilized further to reduce the global burden of vector borne diseases.}, } @article {pmid30426144, year = {2018}, author = {Toscani Field, J and Weinberg, J and Bensch, S and Matta, NE and Valkiūnas, G and Sehgal, RNM}, title = {Delineation of the Genera Haemoproteus and Plasmodium Using RNA-Seq and Multi-gene Phylogenetics.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {646-654}, pmid = {30426144}, issn = {1432-1432}, support = {SC3 GM118210/GM/NIGMS NIH HHS/United States ; MIP-045/2015//Research Council of Lithuania/ ; 1SC3GM118210-01A1//National Institutes of Health/ ; }, abstract = {Members of the order Haemosporida are protist parasites that infect mammals, reptiles and birds. This group includes the causal agents of malaria, Plasmodium parasites, the genera Leucocytozoon and Fallisia, as well as the species rich genus Haemoproteus with its two subgenera Haemoproteus and Parahaemoproteus. Some species of Haemoproteus cause severe disease in avian hosts, and these parasites display high levels of diversity worldwide. This diversity emphasizes the need for accurate evolutionary information. Most molecular studies of wildlife haemosporidians use a bar coding approach by sequencing a fragment of the mitochondrial cytochrome b gene. This method is efficient at differentiating parasite lineages but insufficient for accurate phylogenetic inferences in highly diverse taxa such as haemosporidians. Recent studies have utilized multiple mitochondrial genes (cyt b, cox1 and cox3), sometimes combined with a few apicoplast and nuclear genes. These studies have been highly successful with one notable exception: the evolutionary relationships of the genus Haemoproteus remain unresolved. Here we describe the transcriptome of Haemoproteus columbae and investigate its phylogenetic position recovered from a multi-gene dataset (600 genes). This genomic approach restricts the taxon sampling to 18 species of apicomplexan parasites. We employed Bayesian inference and maximum likelihood methods of phylogenetic analyses and found H. columbae and a representative from the subgenus Parahaemoproteus to be sister taxa. This result strengthens the hypothesis of genus Haemoproteus being monophyletic; however, resolving this question will require sequences of orthologs from, in particular, representatives of Leucocytozoon species.}, } @article {pmid30425375, year = {2018}, author = {}, title = {US elections signal a welcome change for science.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {294}, doi = {10.1038/d41586-018-07409-7}, pmid = {30425375}, issn = {1476-4687}, } @article {pmid30425374, year = {2018}, author = {Abbott, A}, title = {Italy's olive crisis intensifies as deadly tree disease spreads.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {306-307}, doi = {10.1038/d41586-018-07389-8}, pmid = {30425374}, issn = {1476-4687}, } @article {pmid30425373, year = {2018}, author = {Cyranoski, D}, title = {China's crackdown on genetics breaches could deter data sharing.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {301-302}, doi = {10.1038/d41586-018-07222-2}, pmid = {30425373}, issn = {1476-4687}, } @article {pmid30425372, year = {2018}, author = {Ledford, H}, title = {How Facebook and Twitter could be the next disruptive force in clinical trials.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {312-315}, doi = {10.1038/d41586-018-07351-8}, pmid = {30425372}, issn = {1476-4687}, } @article {pmid30425371, year = {2018}, author = {Laurance, W}, title = {If you can't build well, then build nothing at all.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {295}, doi = {10.1038/d41586-018-07348-3}, pmid = {30425371}, issn = {1476-4687}, } @article {pmid30425370, year = {2018}, author = {}, title = {How a simple 'thank you' could improve clinical trials.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {293-294}, doi = {10.1038/d41586-018-07410-0}, pmid = {30425370}, issn = {1476-4687}, } @article {pmid30425369, year = {2018}, author = {Alteri, E and Guizzaro, L}, title = {Be open about drug failures to speed up research.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {317-319}, doi = {10.1038/d41586-018-07352-7}, pmid = {30425369}, issn = {1476-4687}, } @article {pmid30425367, year = {2018}, author = {Reardon, S}, title = {'Invisible' mice reveal anatomical secrets.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {305-306}, doi = {10.1038/d41586-018-07336-7}, pmid = {30425367}, issn = {1476-4687}, } @article {pmid30425366, year = {2018}, author = {}, title = {A massive atom morphs with record-setting speed.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {296}, doi = {10.1038/d41586-018-07376-z}, pmid = {30425366}, issn = {1476-4687}, } @article {pmid30425365, year = {2018}, author = {}, title = {Oil foils corrosion in high-capacity batteries.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {297}, doi = {10.1038/d41586-018-07347-4}, pmid = {30425365}, issn = {1476-4687}, } @article {pmid30425364, year = {2018}, author = {}, title = {Heart-in-a-dish dances to the beat.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {297}, doi = {10.1038/d41586-018-07373-2}, pmid = {30425364}, issn = {1476-4687}, } @article {pmid30425363, year = {2018}, author = {Callaway, E}, title = {Ancient genomics is recasting the story of the Americas' first residents.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {303-304}, doi = {10.1038/d41586-018-07374-1}, pmid = {30425363}, issn = {1476-4687}, } @article {pmid30425362, year = {2018}, author = {Else, H}, title = {Sanger whistle-blowers dispute findings that cleared management of bullying.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {304-305}, doi = {10.1038/d41586-018-07339-4}, pmid = {30425362}, issn = {1476-4687}, } @article {pmid30425361, year = {2018}, author = {Lee, JJ and Maxmen, A and Rehm, J and Tollefson, J}, title = {Science candidates prevail in US midterm elections.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {302-303}, doi = {10.1038/d41586-018-07322-z}, pmid = {30425361}, issn = {1476-4687}, } @article {pmid30425360, year = {2018}, author = {}, title = {'Mining' Bitcoin takes more energy than mining gold.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {296}, doi = {10.1038/d41586-018-07283-3}, pmid = {30425360}, issn = {1476-4687}, } @article {pmid30425359, year = {2018}, author = {}, title = {Thar she blows! Whales seen exhaling from space.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {297}, doi = {10.1038/d41586-018-07284-2}, pmid = {30425359}, issn = {1476-4687}, } @article {pmid30425358, year = {2018}, author = {}, title = {Warming trend spoils Europe's winter wonderlands.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {297}, doi = {10.1038/d41586-018-07321-0}, pmid = {30425358}, issn = {1476-4687}, } @article {pmid30425357, year = {2018}, author = {}, title = {How Mongolia's milk-based empire got its start.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {296-297}, doi = {10.1038/d41586-018-07305-0}, pmid = {30425357}, issn = {1476-4687}, } @article {pmid30425356, year = {2018}, author = {Douglas, AE}, title = {Gut microbes alter the walking activity of fruit flies.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {331-332}, doi = {10.1038/d41586-018-07080-y}, pmid = {30425356}, issn = {1476-4687}, mesh = {Animals ; *Drosophila ; Gastrointestinal Microbiome ; *Walking ; }, } @article {pmid30425355, year = {2018}, author = {Parikh, SM}, title = {Increased synthesis of a coenzyme linked to longevity can combat disease.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {332-333}, doi = {10.1038/d41586-018-07088-4}, pmid = {30425355}, issn = {1476-4687}, mesh = {Coenzymes ; *Longevity ; *NAD ; Records ; }, } @article {pmid30425354, year = {2018}, author = {Lewin, SR}, title = {Combination treatment prevents HIV re-emergence in monkeys.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {333-335}, doi = {10.1038/d41586-018-06818-y}, pmid = {30425354}, issn = {1476-4687}, mesh = {Animals ; *Antibodies ; Extracellular Space ; HIV ; *Haplorhini ; Immunosuppressive Agents ; }, } @article {pmid30425353, year = {2018}, author = {Zhang, J and Zhang, X and Tang, H and Zhang, Q and Hua, X and Ma, X and Zhu, F and Jones, T and Zhu, X and Bowers, J and Wai, CM and Zheng, C and Shi, Y and Chen, S and Xu, X and Yue, J and Nelson, DR and Huang, L and Li, Z and Xu, H and Zhou, D and Wang, Y and Hu, W and Lin, J and Deng, Y and Pandey, N and Mancini, M and Zerpa, D and Nguyen, JK and Wang, L and Yu, L and Xin, Y and Ge, L and Arro, J and Han, JO and Chakrabarty, S and Pushko, M and Zhang, W and Ma, Y and Ma, P and Lv, M and Chen, F and Zheng, G and Xu, J and Yang, Z and Deng, F and Chen, X and Liao, Z and Zhang, X and Lin, Z and Lin, H and Yan, H and Kuang, Z and Zhong, W and Liang, P and Wang, G and Yuan, Y and Shi, J and Hou, J and Lin, J and Jin, J and Cao, P and Shen, Q and Jiang, Q and Zhou, P and Ma, Y and Zhang, X and Xu, R and Liu, J and Zhou, Y and Jia, H and Ma, Q and Qi, R and Zhang, Z and Fang, J and Fang, H and Song, J and Wang, M and Dong, G and Wang, G and Chen, Z and Ma, T and Liu, H and Dhungana, SR and Huss, SE and Yang, X and Sharma, A and Trujillo, JH and Martinez, MC and Hudson, M and Riascos, JJ and Schuler, M and Chen, LQ and Braun, DM and Li, L and Yu, Q and Wang, J and Wang, K and Schatz, MC and Heckerman, D and Van Sluys, MA and Souza, GM and Moore, PH and Sankoff, D and VanBuren, R and Paterson, AH and Nagai, C and Ming, R}, title = {Publisher Correction: Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1754}, doi = {10.1038/s41588-018-0293-7}, pmid = {30425353}, issn = {1546-1718}, abstract = {In the version of this article originally published, the accession codes listed in the data availability section were incorrect and the section was incomplete. The text for this section should have read "The genome assembly and gene annotation have been deposited in the NCBI database under accession number QVOL00000000, BioProject number PRJNA483885 and BioSample number SAMN09753102. The data can also be downloaded from the following link: http://www.life.illinois.edu/ming/downloads/Spontaneum_genome/ ." The errors have been corrected in the HTML and PDF versions of the article.}, } @article {pmid30425342, year = {2018}, author = {Riller, U and Poelchau, MH and Rae, ASP and Schulte, FM and Collins, GS and Melosh, HJ and Grieve, RAF and Morgan, JV and Gulick, SPS and Lofi, J and Diaw, A and McCall, N and Kring, DA and , }, title = {Author Correction: Rock fluidization during peak-ring formation of large impact structures.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {E36}, doi = {10.1038/s41586-018-0748-0}, pmid = {30425342}, issn = {1476-4687}, abstract = {In this Article, the middle initial of author Kosei E. Yamaguchi (of the IODP-ICDP Expedition 364 Science Party) was missing and his affiliation is to Toho University (not Tohu University). These errors have been corrected online.}, } @article {pmid30425333, year = {2018}, author = {Lewitus, E and Bittner, L and Malviya, S and Bowler, C and Morlon, H}, title = {Author Correction: Clade-specific diversification dynamics of marine diatoms since the Jurassic.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1993}, doi = {10.1038/s41559-018-0740-y}, pmid = {30425333}, issn = {2397-334X}, abstract = {In the version of this Article originally published, the authors did not give credit to David G. Mann for the four microscopic images used in Fig. 1a. This has now been amended in all versions of the Article.}, } @article {pmid30425181, year = {2018}, author = {Amundson, R and Biardeau, L}, title = {Opinion: Soil carbon sequestration is an elusive climate mitigation tool.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11652-11656}, pmid = {30425181}, issn = {1091-6490}, } @article {pmid30425178, year = {2018}, author = {Novembre, G and Iannetti, GD}, title = {Tagging the musical beat: Neural entrainment or event-related potentials?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11002-E11003}, pmid = {30425178}, issn = {1091-6490}, mesh = {Auditory Perception ; *Evoked Potentials ; *Music ; }, } @article {pmid30425177, year = {2018}, author = {Lenc, T and Keller, PE and Varlet, M and Nozaradan, S}, title = {Reply to Novembre and Iannetti: Conceptual and methodological issues.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11004}, pmid = {30425177}, issn = {1091-6490}, mesh = {*Music ; *Sound ; }, } @article {pmid30425176, year = {2018}, author = {Charra, F and Berthelot, P and Bergheau, F}, title = {Penicillins' defined daily doses must be changed.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11432}, doi = {10.1073/pnas.1816558115}, pmid = {30425176}, issn = {1091-6490}, mesh = {*Anti-Bacterial Agents ; *Penicillins ; Physiological Phenomena ; }, } @article {pmid30425175, year = {2018}, author = {Klein, EY and Tseng, KK and Levin, SA and Goossens, H and Laxminarayan, R}, title = {Reply to Charra et al.: Global longitudinal assessment of 2019 changes in defined daily doses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11433-E11435}, doi = {10.1073/pnas.1817182115}, pmid = {30425175}, issn = {1091-6490}, mesh = {*Anti-Bacterial Agents ; *Physiological Phenomena ; }, } @article {pmid30425174, year = {2018}, author = {O'Sullivan, JN}, title = {Is failure to develop due to fundamentally different economic pathways or simply too much population growth?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11200-E11201}, pmid = {30425174}, issn = {1091-6490}, } @article {pmid30425173, year = {2018}, author = {Cumming, GS and von Cramon-Taubadel, S}, title = {Reply to O'Sullivan: Wicked problems demand sophisticated understandings of complexity and feedbacks, not focus on a single variable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11202-E11203}, pmid = {30425173}, issn = {1091-6490}, } @article {pmid30425172, year = {2018}, author = {Wannier, TM and Gillespie, SK and Hutchins, N and McIsaac, RS and Wu, SY and Shen, Y and Campbell, RE and Brown, KS and Mayo, SL}, title = {Monomerization of far-red fluorescent proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11294-E11301}, pmid = {30425172}, issn = {1091-6490}, support = {R21 EB018579/EB/NIBIB NIH HHS/United States ; }, abstract = {Anthozoa-class red fluorescent proteins (RFPs) are frequently used as biological markers, with far-red (λem ∼ 600-700 nm) emitting variants sought for whole-animal imaging because biological tissues are more permeable to light in this range. A barrier to the use of naturally occurring RFP variants as molecular markers is that all are tetrameric, which is not ideal for cell biological applications. Efforts to engineer monomeric RFPs have typically produced dimmer and blue-shifted variants because the chromophore is sensitive to small structural perturbations. In fact, despite much effort, only four native RFPs have been successfully monomerized, leaving the majority of RFP biodiversity untapped in biomarker development. Here we report the generation of monomeric variants of HcRed and mCardinal, both far-red dimers, and describe a comprehensive methodology for the monomerization of red-shifted oligomeric RFPs. Among the resultant variants is mKelly1 (emission maximum, λem = 656 nm), which, along with the recently reported mGarnet2 [Matela G, et al. (2017) Chem Commun (Camb) 53:979-982], forms a class of bright, monomeric, far-red FPs.}, } @article {pmid30425171, year = {2018}, author = {Payne, S and McCarthy, S and Johnson, T and North, E and Blum, P}, title = {Nonmutational mechanism of inheritance in the Archaeon Sulfolobus solfataricus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12271-12276}, pmid = {30425171}, issn = {1091-6490}, abstract = {Epigenetic phenomena have not yet been reported in archaea, which are presumed to use a classical genetic process of heritability. Here, analysis of independent lineages of Sulfolobus solfataricus evolved for enhanced fitness implicated a non-Mendelian basis for trait inheritance. The evolved strains, called super acid-resistant Crenarchaeota (SARC), acquired traits of extreme acid resistance and genome stability relative to their wild-type parental lines. Acid resistance was heritable because it was retained regardless of extensive passage without selection. Despite the hereditary pattern, in one strain, it was impossible for these SARC traits to result from mutation because its resequenced genome had no mutation. All strains also had conserved, heritable transcriptomes implicated in acid resistance. In addition, they had improved genome stability with absent or greatly decreased mutation and transposition relative to a passaged control. A mechanism that would confer these traits without DNA sequence alteration could involve posttranslationally modified archaeal chromatin proteins. To test this idea, homologous recombination with isogenic DNA was used to perturb native chromatin structure. Recombination at up-regulated loci from the heritable SARC transcriptome reduced acid resistance and gene expression in the majority of recombinants. In contrast, recombination at a control locus that was not part of the heritable transcriptome changed neither acid resistance nor gene expression. Variation in the amount of phenotypic and expression changes across individuals was consistent with Rad54-dependent chromatin remodeling that dictated crossover location and branch migration. These data support an epigenetic model implicating chromatin structure as a contributor to heritable traits.}, } @article {pmid30425170, year = {2018}, author = {Breska, A and Ivry, RB}, title = {Double dissociation of single-interval and rhythmic temporal prediction in cerebellar degeneration and Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12283-12288}, pmid = {30425170}, issn = {1091-6490}, support = {R01 NS092079/NS/NINDS NIH HHS/United States ; R01 NS105839/NS/NINDS NIH HHS/United States ; }, abstract = {Predicting the timing of upcoming events is critical for successful interaction in a dynamic world, and is recognized as a key computation for attentional orienting. Temporal predictions can be formed when recent events define a rhythmic structure, as well as in aperiodic streams or even in isolation, when a specified interval is known from previous exposure. However, whether predictions in these two contexts are mediated by a common mechanism, or by distinct, context-dependent mechanisms, is highly controversial. Moreover, although the basal ganglia and cerebellum have been linked to temporal processing, the role of these subcortical structures in temporal orienting of attention is unclear. To address these issues, we tested individuals with cerebellar degeneration or Parkinson's disease, with the latter serving as a model of basal ganglia dysfunction, on temporal prediction tasks in the subsecond range. The participants performed a visual detection task in which the onset of the target was predictable, based on either a rhythmic stream of stimuli, or a single interval, specified by two events that occurred within an aperiodic stream. Patients with cerebellar degeneration showed no benefit from single-interval cuing but preserved benefit from rhythm cuing, whereas patients with Parkinson's disease showed no benefit from rhythm cuing but preserved benefit from single-interval cuing. This double dissociation provides causal evidence for functionally nonoverlapping mechanisms of rhythm- and interval-based temporal prediction for attentional orienting, and establishes the separable contributions of the cerebellum and basal ganglia to these functions, suggesting a mechanistic specialization across timing domains.}, } @article {pmid30424821, year = {2018}, author = {Singh, NK and Wood, JM and Karouia, F and Venkateswaran, K}, title = {Succession and persistence of microbial communities and antimicrobial resistance genes associated with International Space Station environmental surfaces.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {204}, pmid = {30424821}, issn = {2049-2618}, support = {19-12829-26//2012 Space Biology NNH12ZTT001N/ ; }, abstract = {BACKGROUND: The International Space Station (ISS) is an ideal test bed for studying the effects of microbial persistence and succession on a closed system during long space flight. Culture-based analyses, targeted gene-based amplicon sequencing (bacteriome, mycobiome, and resistome), and shotgun metagenomics approaches have previously been performed on ISS environmental sample sets using whole genome amplification (WGA). However, this is the first study reporting on the metagenomes sampled from ISS environmental surfaces without the use of WGA. Metagenome sequences generated from eight defined ISS environmental locations in three consecutive flights were analyzed to assess the succession and persistence of microbial communities, their antimicrobial resistance (AMR) profiles, and virulence properties. Metagenomic sequences were produced from the samples treated with propidium monoazide (PMA) to measure intact microorganisms.

RESULTS: The intact microbial communities detected in Flight 1 and Flight 2 samples were significantly more similar to each other than to Flight 3 samples. Among 318 microbial species detected, 46 species constituting 18 genera were common in all flight samples. Risk group or biosafety level 2 microorganisms that persisted among all three flights were Acinetobacter baumannii, Haemophilus influenzae, Klebsiella pneumoniae, Salmonella enterica, Shigella sonnei, Staphylococcus aureus, Yersinia frederiksenii, and Aspergillus lentulus. Even though Rhodotorula and Pantoea dominated the ISS microbiome, Pantoea exhibited succession and persistence. K. pneumoniae persisted in one location (US Node 1) of all three flights and might have spread to six out of the eight locations sampled on Flight 3. The AMR signatures associated with β-lactam, cationic antimicrobial peptide, and vancomycin were detected. Prominent virulence factors were cobalt-zinc-cadmium resistance and multidrug-resistance efflux pumps.

CONCLUSIONS: There was an increase in AMR and virulence gene factors detected over the period sampled, and metagenome sequences of human pathogens persisted over time. Comparative analysis of the microbial compositions of ISS with Earth analogs revealed that the ISS environmental surfaces were different in microbial composition. Metagenomics coupled with PMA treatment would help future space missions to estimate problematic risk group microbial pathogens. Cataloging AMR/virulence characteristics, succession, accumulation, and persistence of microorganisms would facilitate the development of suitable countermeasures to reduce their presence in the closed built environment.}, } @article {pmid30424806, year = {2018}, author = {Kaliannan, K and Robertson, RC and Murphy, K and Stanton, C and Kang, C and Wang, B and Hao, L and Bhan, AK and Kang, JX}, title = {Estrogen-mediated gut microbiome alterations influence sexual dimorphism in metabolic syndrome in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {205}, pmid = {30424806}, issn = {2049-2618}, abstract = {BACKGROUND: Understanding the mechanism of the sexual dimorphism in susceptibility to obesity and metabolic syndrome (MS) is important for the development of effective interventions for MS.

RESULTS: Here we show that gut microbiome mediates the preventive effect of estrogen (17β-estradiol) on metabolic endotoxemia (ME) and low-grade chronic inflammation (LGCI), the underlying causes of MS and chronic diseases. The characteristic profiles of gut microbiome observed in female and 17β-estradiol-treated male and ovariectomized mice, such as decreased Proteobacteria and lipopolysaccharide biosynthesis, were associated with a lower susceptibility to ME, LGCI, and MS in these animals. Interestingly, fecal microbiota-transplant from male mice transferred the MS phenotype to female mice, while antibiotic treatment eliminated the sexual dimorphism in MS, suggesting a causative role of the gut microbiome in this condition. Moreover, estrogenic compounds such as isoflavones exerted microbiome-modulating effects similar to those of 17β-estradiol and reversed symptoms of MS in the male mice. Finally, both expression and activity of intestinal alkaline phosphatase (IAP), a gut microbiota-modifying non-classical anti-microbial peptide, were upregulated by 17β-estradiol and isoflavones, whereas inhibition of IAP induced ME and LGCI in female mice, indicating a critical role of IAP in mediating the effects of estrogen on these parameters.

CONCLUSIONS: In summary, we have identified a previously uncharacterized microbiome-based mechanism that sheds light upon sexual dimorphism in the incidence of MS and that suggests novel therapeutic targets and strategies for the management of obesity and MS in males and postmenopausal women.}, } @article {pmid30424744, year = {2018}, author = {Li, P and Xin, W and Xia, S and Luo, Y and Chen, Z and Jin, D and Gao, S and Yang, H and Ji, B and Wang, H and Yan, Y and Kang, L and Wang, J}, title = {MALDI-TOF mass spectrometry-based serotyping of V. parahaemolyticus isolated from the Zhejiang province of China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {185}, pmid = {30424744}, issn = {1471-2180}, support = {R01 AA021402/AA/NIAAA NIH HHS/United States ; 2016YFC1202400//the Special Key Project of Biosafety Technologies for the National Major Research & Development Program of China/ ; 2014AA021402//the National Hi-Tech Research and Development (863) Program of China/ ; }, abstract = {BACKGROUND: Vibrio parahaemolyticus is as an important food-borne pathogen circulating in China. Since 1996, the core serotype has become O3:K6, which has specific genetic markers. This serotype causes the majority of outbreaks worldwide. Until now, nearly 21 serotypes were considered as serovariants of O3:K6. Among these, O4:K68, O1:K25 and O1:KUT have caused pandemic outbreaks. O4:K8, a serovariant of O3:K6, has become the second most dominant serotype circulating in China after O3:K6. In this study, we report the use of matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze and characterize 146 V. parahaemolyticus isolates belonging to 23 serotypes.

RESULTS: Upon mass spectral analysis, isolates belonging to O4:K8 formed a distinct group among the five main pandemic groups (O3:K6, O4:K8, O4:K68, O1:K25 and O1:KUT). Two major protein peaks (m/z 4383 and 4397) were significantly different between serotype O4:K8 and the four other pandemic strains. Both of these peaks were present in 32 out of 36 O4:K8 isolates, but were absent in 105 out of 110 non-O4:K8 isolates. These peaks were also absent in all 74 pandemic serotypes (O3:K6, O4:K68, O1:K25 and O1:KUT).

CONCLUSION: Our results highlight the threat of O4:K8 forming a distinct group, which differs significantly from pandemic serotypes on the proteomic level. The use of MALDI-TOF MS has not been reported before in a study of this nature. Mass spectrum peaks at m/z 4383 and 4397 may be specific for O4:K8. However, we cannot conclude that MALDI-TOF MS can be used to serotype V. parahaemolyticus.}, } @article {pmid30424734, year = {2018}, author = {Jung, JY and Ahn, JH and Schachtman, DP}, title = {CC-type glutaredoxins mediate plant response and signaling under nitrate starvation in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {281}, pmid = {30424734}, issn = {1471-2229}, support = {2017R1A2B3009624//National Research Foundation of Korea/ ; }, mesh = {Anion Transport Proteins/genetics/metabolism ; Arabidopsis/drug effects/*enzymology/genetics/physiology ; Arabidopsis Proteins/genetics/metabolism ; Chlorophyll/metabolism ; *Gene Expression Regulation, Plant ; Glutaredoxins/genetics/*metabolism ; Hydrogen Peroxide/pharmacology ; Nitrates/*metabolism ; Nitrogen/*metabolism ; Plant Roots/drug effects/enzymology/genetics/physiology ; Reactive Oxygen Species/metabolism ; Seedlings/drug effects/enzymology/genetics/physiology ; *Signal Transduction ; }, abstract = {BACKGROUND: Nitrogen is an essential nutrient in plants. Despite the importance of nitrogen for plant growth and agricultural productivity, signal transduction pathways in response to nitrate starvation have not been fully elucidated in plants.

RESULTS: Gene expression analysis and ectopic expression were used to discover that many CC-type glutaredoxins (ROXYs) are differentially expressed in response to nitrate deprivation. A gain-of-function approach showed that ROXYs may play a role in nutrient sensing through the regulation of chlorophyll content, root hair growth, and transcription of nitrate-related genes such as NRT2.1 under low or high nitrate conditions. Reactive oxygen species (ROS) were produced in plant roots under nitrate starvation and H2O2 treatment differentially regulated the expression of the ROXYs, suggesting the involvement of ROS in signaling pathways under nitrate deficiency.

CONCLUSION: This work adds to what is known about nitrogen sensing and signaling through the findings that the ROXYs and ROS are likely to be involved in the nitrate deprivation signaling pathway.}, } @article {pmid30424733, year = {2018}, author = {Jurak, E and Suzuki, H and van Erven, G and Gandier, JA and Wong, P and Chan, K and Ho, CY and Gong, Y and Tillier, E and Rosso, MN and Kabel, MA and Miyauchi, S and Master, ER}, title = {Dynamics of the Phanerochaete carnosa transcriptome during growth on aspen and spruce.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {815}, pmid = {30424733}, issn = {1471-2164}, support = {ORF-RE-05-005//Government of Ontario/ ; 648925//European Research Council/International ; }, abstract = {BACKGROUND: The basidiomycete Phanerochaete carnosa is a white-rot species that has been mainly isolated from coniferous softwood. Given the particular recalcitrance of softwoods to bioconversion, we conducted a comparative transcriptomic analysis of P. carnosa following growth on wood powder from one softwood (spruce; Picea glauca) and one hardwood (aspen; Populus tremuloides). P. carnosa was grown on each substrate for over one month, and mycelia were harvested at five time points for total RNA sequencing. Residual wood powder was also analyzed for total sugar and lignin composition.

RESULTS: Following a slightly longer lag phase of growth on spruce, radial expansion of the P. carnosa colony was similar on spruce and aspen. Consistent with this observation, the pattern of gene expression by P. carnosa on each substrate converged following the initial adaptation. On both substrates, highest transcript abundances were attributed to genes predicted to encode manganese peroxidases (MnP), along with auxiliary activities from carbohydrate-active enzyme (CAZy) families AA3 and AA5. In addition, a lytic polysaccharide monooxygenase from family AA9 was steadily expressed throughout growth on both substrates. P450 sequences from clans CPY52 and CYP64 accounted for 50% or more of the most highly expressed P450s, which were also the P450 clans that were expanded in the P. carnosa genome relative to other white-rot fungi.

CONCLUSIONS: The inclusion of five growth points and two wood substrates was important to revealing differences in the expression profiles of specific sequences within large glycoside hydrolase families (e.g., GH5 and GH16), and permitted co-expression analyses that identified new targets for study, including non-catalytic proteins and proteins with unknown function.}, } @article {pmid30424729, year = {2018}, author = {Song, H and Guo, Z and Chen, T and Sun, J and Yang, G}, title = {Genome-wide identification of LRR-containing sequences and the response of these sequences to nematode infection in Arachis duranensis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {279}, pmid = {30424729}, issn = {1471-2229}, mesh = {Amino Acid Sequence ; Animals ; Arachis/*genetics/parasitology ; *Disease Resistance ; Nematoda/*physiology ; Organ Specificity ; Phylogeny ; Plant Diseases/*immunology/parasitology ; Plant Proteins/genetics ; Protein Domains ; Proteins/genetics ; }, abstract = {BACKGROUND: Leucine-rich repeat (LRR)-containing genes are involved in responses to various diseases. Recently, RNA-seq data from A. duranensis after nematode (Meloidogyne arenaria) infection were released. However, the number of LRR-containing genes present in A. duranensis and the response of LRR-containing genes to nematode infection are poorly understood.

RESULTS: In this study, we found 509 amino acid sequences containing nine types of LRR domains in A. duranensis. The inferred phylogenetic relationships revealed that the nine types of LRR domains had two originations. The inferred selective pressure was mainly consistent with LRR domains undergoing purifying selection. Twenty-one LRR-containing genes were associated with possible resistance to nematode infection after 3, 6, and 9 days. Among them, Aradu.T5WNW, Aradu.JM17V, and Aradu.MKP1A were up-regulate at these three time points, while Aradu.QD5DS and Aradu.M0ENQ were up-regulated 6 and 9 days after nematode infection. The expression of the above mentioned five genes was significantly and negatively correlated with the number of LRR8 domain, indicating that fewer LRR8 domains are associated with the promotion of LRR-containing genes that resist nematode infection. Patterns of co-expression and cis-acting elements indicated that WRKY possibly regulate the responses of LRR-containing genes to nematode infection and that expansin genes may work together with LRR-containing genes in response to nematode infection.

CONCLUSIONS: We identified the number and type of LRR-containing genes in A. duranensis. The LRR-containing genes that were found appear to be involved in responses to nematode infection. The number of LRR8 domains was negatively correlated with expression after nematode infection. The WRKY transcription factor may regulate resistance to nematode infection based on LRR-containing genes. Our results could improve the understanding of resistance to nematodes and molecular breeding in peanuts.}, } @article {pmid30424728, year = {2018}, author = {Plummer, EL and Bulach, DM and Murray, GL and Jacobs, SE and Tabrizi, SN and Garland, SM and , }, title = {Gut microbiota of preterm infants supplemented with probiotics: sub-study of the ProPrems trial.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {184}, pmid = {30424728}, issn = {1471-2180}, support = {454629//National Health and Medical Research Council/ ; NA//The Royal Women's Hospital Foundation, Melbourne, Australia/ ; NA//Angior Family Foundation/ ; }, abstract = {BACKGROUND: The ProPrems trial, a multi-center, double-blind, placebo-controlled randomized trial, previously reported a 54% reduction in necrotizing enterocolitis (NEC) of Bell stage 2 or more from 4.4 to 2.0% in 1099 infants born before 32 completed weeks' gestation and weighing < 1500 g, receiving probiotic supplementation (with Bifidobacterium longum subsp. infantis BB-02, Streptococcus thermophilus TH-4 and Bifidobacterium animalis subsp. lactis BB-12). This sub-study investigated the effect of probiotic supplementation on the gut microbiota in a cohort of very preterm infants in ProPrems.

RESULTS: Bifidobacterium was found in higher abundance in infants who received the probiotics (AOR 17.22; 95% CI, 3.49-84.99, p < 0.001) as compared to the placebo group, and Enterococcus was reduced in infants receiving the probiotic during the supplementation period (AOR 0.27; 95% CI, 0.09-0.82, p = 0.02).

CONCLUSION: Probiotic supplementation with BB-02, TH-4 and BB-12 from soon after birth increased the abundance of Bifidobacterium in the gut microbiota of very preterm infants. Increased abundance of Bifidobacterium soon after birth may be associated with reducing the risk of NEC in very preterm infants.}, } @article {pmid30424726, year = {2018}, author = {Reis-Cunha, JL and Baptista, RP and Rodrigues-Luiz, GF and Coqueiro-Dos-Santos, A and Valdivia, HO and de Almeida, LV and Cardoso, MS and D'Ávila, DA and Dias, FHC and Fujiwara, RT and Galvão, LMC and Chiari, E and Cerqueira, GC and Bartholomeu, DC}, title = {Whole genome sequencing of Trypanosoma cruzi field isolates reveals extensive genomic variability and complex aneuploidy patterns within TcII DTU.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {816}, pmid = {30424726}, issn = {1471-2164}, abstract = {BACKGROUND: Trypanosoma cruzi, the etiologic agent of Chagas disease, is currently divided into six discrete typing units (DTUs), named TcI-TcVI. TcII is among the major DTUs enrolled in human infections in South America southern cone, where it is associated with severe cardiac and digestive symptoms. Despite the importance of TcII in Chagas disease epidemiology and pathology, so far, no genome-wide comparisons of the mitochondrial and nuclear genomes of TcII field isolates have been performed to track the variability and evolution of this DTU in endemic regions.

RESULTS: In the present work, we have sequenced and compared the whole nuclear and mitochondrial genomes of seven TcII strains isolated from chagasic patients from the central and northeastern regions of Minas Gerais, Brazil, revealing an extensive genetic variability within this DTU. A comparison of the phylogeny based on the nuclear or mitochondrial genomes revealed that the majority of branches were shared by both sequences. The subtle divergences in the branches are probably consequence of mitochondrial introgression events between TcII strains. Two T. cruzi strains isolated from patients living in the central region of Minas Gerais, S15 and S162a, were clustered in the nuclear and mitochondrial phylogeny analysis. These two strains were isolated from the other five by the Espinhaço Mountains, a geographic barrier that could have restricted the traffic of insect vectors during T. cruzi evolution in the Minas Gerais state. Finally, the presence of aneuploidies was evaluated, revealing that all seven TcII strains have a different pattern of chromosomal duplication/loss.

CONCLUSIONS: Analysis of genomic variability and aneuploidies suggests that there is significant genomic variability within Minas Gerais TcII strains, which could be exploited by the parasite to allow rapid selection of favorable phenotypes. Also, the aneuploidy patterns vary among T. cruzi strains and does not correlate with the nuclear phylogeny, suggesting that chromosomal duplication/loss are recent and frequent events in the parasite evolution.}, } @article {pmid30424724, year = {2018}, author = {Mourad, AMI and Sallam, A and Belamkar, V and Mahdy, E and Bakheit, B and Abo El-Wafaa, A and Stephen Baenziger, P}, title = {Genetic architecture of common bunt resistance in winter wheat using genome-wide association study.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {280}, pmid = {30424724}, issn = {1471-2229}, mesh = {Basidiomycota/*physiology ; Disease Resistance/*genetics ; *Genetic Variation ; *Genome-Wide Association Study ; Genotype ; Linkage Disequilibrium ; Molecular Sequence Annotation ; Phenotype ; Plant Diseases/*immunology/microbiology ; Quantitative Trait Loci/genetics ; Triticum/*genetics/immunology ; }, abstract = {BACKGROUND: Common bunt (caused by Tilletia caries and T. foetida) has been considered as a major disease in wheat (Triticum aestivum) following rust (Puccinia spp.) in the Near East and is economically important in the Great Plains, USA. Despite the fact that it can be easily controlled using seed treatment with fungicides, fungicides often cannot or may not be used in organic and low-input fields. Planting common bunt resistant genotypes is an alternative.

RESULTS: To identify resistance genes for Nebraska common bunt race, the global set of differential lines were inoculated. Nine differential lines carrying nine different genes had 0% infected heads and seemed to be resistant to Nebraska race. To understand the genetic basis of the resistance in Nebraska winter wheat, a set of 330 genotypes were inoculated and evaluated under field conditions in two locations. Out of the 330 genotypes, 62 genotypes had different degrees of resistance. Moreover, plant height, chlorophyll content and days to heading were scored in both locations. Using genome-wide association study, 123 SNPs located on fourteen chromosomes were identified to be associated with the resistance. Different degrees of linkage disequilibrium was found among the significant SNPs and they explained 1.00 to 9.00% of the phenotypic variance, indicating the presence of many minor QTLs controlling the resistance.

CONCLUSION: Based on the chromosomal location of some of the known genes, some SNPs may be associated with Bt1, Bt6, Bt11 and Bt12 resistance loci. The remaining significant SNPs may be novel alleles that were not reported previously. Common bunt resistance seems to be an independent trait as no correlation was found between a number of infected heads and chlorophyll content, days to heading or plant height.}, } @article {pmid30423441, year = {2019}, author = {de Mazancourt, V and Klotz, W and Marquet, G and Mos, B and Rogers, DC and Keith, P}, title = {The complex study of complexes: The first well-supported phylogeny of two species complexes within genus Caridina (Decapoda: Caridea: Atyidae) sheds light on evolution, biogeography, and habitat.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {164-180}, doi = {10.1016/j.ympev.2018.11.002}, pmid = {30423441}, issn = {1095-9513}, abstract = {Atyid shrimps, a key component of tropical freshwater ecosystems, face multiple anthropogenic threats and thus need special attention. With more than 300 described species, the genus Caridina is the most speciose of all the Caridea infra-order. Caridina spp. occupy diverse habitats in tropical freshwaters of the Indo-West Pacific region. Several species complexes have been recognized, based on common morphological features, but little is known about how well these morphological characteristics align with phylogenetic characteristics. Furthermore, no phylogeny of the genus Caridina published so far has provided well-resolved and supported relationships among different species, thus impeding the possibility of proposing evolutionary hypotheses. In this study we used next generation sequencing (NGS) to provide new insights into the phylogenetic relationships among the genus Caridina, focusing on two complexes: 'Caridina nilotica' and 'Caridina weberi'. We collected 92 specimens belonging to these two groups from most of their known geographical range, representing 50 species, for which we sequenced seven mitochondrial genes and two nuclear markers using ion torrent NGS. We performed a phylogenetic analysis, which yielded the first well-supported tree for the genus Caridina. On this tree were mapped the geographic ranges and the habitats used by the different species, and a time calibration was tested. We found the driving factors that most likely account for separation of clades are differences in habitat and to a lesser extent geography. This work provides new insights into the taxonomy of this group and identifies opportunities for further studies in order to fill knowledge gaps that currently impede the management and conservation of atyid species.}, } @article {pmid30423440, year = {2019}, author = {Margos, G and Becker, NS and Fingerle, V and Sing, A and Ramos, JA and Carvalho, IL and Norte, AC}, title = {Core genome phylogenetic analysis of the avian associated Borrelia turdi indicates a close relationship to Borrelia garinii.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {93-98}, doi = {10.1016/j.ympev.2018.10.044}, pmid = {30423440}, issn = {1095-9513}, abstract = {Borrelia burgdorferi sensu lato comprises a species complex of tick-transmitted bacteria that includes the agents of human Lyme borreliosis. Borrelia turdi is a genospecies of this complex that exists in cryptic transmission cycles mainly between ornithophilic tick vectors and their avian hosts. The species has been originally discovered in avian transmission cycles in Asia but has increasingly been found in Europe. Next generation sequencing was used to sequence the genome of B. turdi isolates obtained from ticks feeding on birds in Portugal to better understand the evolution and phylogenetic relationship of this avian and ornithophilic tick-associated genospecies. Here we use draft genomes of these B. turdi isolates for comparative analysis and to determine the taxonomic position within the B. burgdorferi s.l. species complex. The main chromosomes showed a maximum similarity of 93% to other Borrelia species whilst most plasmids had lower similarities. All three isolates had nine or 10 plasmids and, interestingly, one plasmid with a novel partitioning protein; this plasmid was termed lp30. Phylogenetic analysis of multilocus sequence typing housekeeping genes and 113 single copy orthologous genes revealed that the isolates clustered according to their classification as B. turdi. In phylogenies generated from these 113 genes the isolates cluster together with other Eurasian genospecies and form a sister clade to the avian associated B. garinii and the rodent associated B. bavariensis. These findings show that Borrelia species maintained in cryptic ecological cycles need to be included to fully understand the complex ecology and evolutionary history of this bacterial species complex.}, } @article {pmid30423439, year = {2019}, author = {Mikkelsen, NT and Todt, C and Kocot, KM and Halanych, KM and Willassen, E}, title = {Molecular phylogeny of Caudofoveata (Mollusca) challenges traditional views.}, journal = {Molecular phylogenetics and evolution}, volume = {132}, number = {}, pages = {138-150}, doi = {10.1016/j.ympev.2018.10.037}, pmid = {30423439}, issn = {1095-9513}, abstract = {The shell-less, worm-shaped Caudofoveata (=Chaetodermomorpha) is one of the least known groups of molluscs. The taxon consists of 141 recognized species found from intertidal environments to the deep-sea where they live burrowing in sediment. Evolutionary relationships of the group have been debated, but few studies based on morphological or molecular data have investigated the phylogeny of the group. Here we use molecular phylogenetics to resolve relationships among and within families of Caudofoveata. Phylogenetic analyses were performed using selected mitochondrial and nuclear genes from species from all recognized families of Caudofoveata. In resulting trees and contrary to traditional views, Prochaetodermatidae forms the sister clade to a clade containing the other two currently recognized families, Chaetodermatidae and Limifossoridae. The monophyly of Prochaetodermatidae is highly supported, but Limifossoridae and Chaetodermatidae are not recovered as monophyletic. Most of the caudofoveate genera are also not recovered as monophyletic in our analyses. Thus results from our molecular data suggest that the current classification of Caudofoveata is in need of revision, and indicate evolutionary scenarios that differ from previously proposed hypotheses based on morphology.}, } @article {pmid30423438, year = {2019}, author = {Espeland, M and Breinholt, JW and Barbosa, EP and Casagrande, MM and Huertas, B and Lamas, G and Marín, MA and Mielke, OHH and Miller, JY and Nakahara, S and Tan, D and Warren, AD and Zacca, T and Kawahara, AY and Freitas, AVL and Willmott, KR}, title = {Four hundred shades of brown: Higher level phylogeny of the problematic Euptychiina (Lepidoptera, Nymphalidae, Satyrinae) based on hybrid enrichment data.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {116-124}, doi = {10.1016/j.ympev.2018.10.039}, pmid = {30423438}, issn = {1095-9513}, abstract = {Relationships within satyrine butterflies have been notoriously difficult to resolve using both morphology and Sanger sequencing methods, and this is particularly true for the mainly Neotropical subtribe Euptychiina, which contains about 400 described species. Known larvae of Euptychiina feed on grasses and sedges, with the exception of the genus Euptychia, which feed on mosses and lycopsids, and the butterflies occur widely in rainforest, cloudforest and grassland habitats, where they are often abundant. Several previous molecular and morphological studies have made significant progress in tackling the systematics of the group, but many relationships remain unresolved, with long-branch-attraction artifacts being a major problem. Additionally, the monophyly of the clade remains uncertain, with Euptychia possibly not being closely related to the remainder of the clade. Here we present a backbone phylogeny of the subtribe based on 106 taxa, 368 nuclear loci, and over 180,000 bps obtained through hybrid enrichment. Using both concatenation and species tree approaches (IQ-TREE, EXABAYES, ASTRAL), we can for the first time strongly confirm the monophyly of Euptychiina with Euptychia being the sister group to the remainder of the clade. The Euptychiina is divided into nine well supported clades, but the placement of a few genera such as Hermeuptychia, Pindis and the Chloreuptychia catharina group still remain uncertain. As partially indicated in previous studies, the genera Cissia, Chloreuptychia, Magneuptychia, Megisto, Splendeuptychia and Euptychoides, among others, were found to be highly polyphyletic and revisions are in preparation. The phylogeny will provide a strong backbone for the analysis of datasets in development that are much more taxonomically comprehensive but have orders of magnitude fewer loci. This study therefore represents a critical step towards resolving the higher classification and studying the evolution of this highly diverse lineage.}, } @article {pmid30422392, year = {2018}, author = {Van den Beuken, TPG and Duinmeijer, CC and Smallegange, IM}, title = {Costs of weaponry: unarmed males sire more offspring than armed males in a male-dimorphic mite.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13402}, pmid = {30422392}, issn = {1420-9101}, support = {864.13.005//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, abstract = {Morphological structures used as weapons in male-male competition are not only costly to develop but are also probably costly to maintain during adulthood. Therefore, having weapons could reduce the energy available for other fitness-enhancing actions, such as post-copulatory investment. We tested the hypothesis that armed males make lower post-copulatory investments than unarmed males, and that this difference will be most pronounced under food-limited conditions. We performed two experiments using the male-dimorphic bulb mite Rhizoglyphus robini, in which males are either armed 'fighters' or unarmed 'scramblers'. Firstly, we tested whether fighters and scramblers differed in their reproductive output after being starved or fed for one or 2 weeks. Secondly, we measured the reproductive output of scramblers and fighters (starved or fed) after one, two or three consecutive matings. Scramblers sired more offspring than fighters after 1 week, but scramblers and fighters only sired a few offspring after 2 weeks. Scramblers also sired more offspring than fighters at the first mating, and males rarely sired offspring after consecutive matings. Contrary to our hypothesis, the fecundity of starved and fed males did not differ. The higher reproductive output of scramblers suggests that, regardless of nutritional state, scramblers make larger post-copulatory investments than fighters. Alternatively, (cryptic) female choice generally favours scramblers. Why the morphs differed in their reproductive output is unclear. Neither morph performed well relatively late in life or after multiple matings. It remains to be investigated to what extent the apparent scrambler advantage contributes to the maintenance and evolution of male morph expression.}, } @article {pmid30422105, year = {2019}, author = {Zhang, XJ and Yao, Q and Wang, YH and Yang, SZ and Feng, GD and Zhu, HH}, title = {Lysobacter silvisoli sp. nov., isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {93-98}, doi = {10.1099/ijsem.0.003105}, pmid = {30422105}, issn = {1466-5034}, abstract = {A yellow-pigmented, Gram-stain-negative, gliding and rod-shaped bacterial strain, designated zong2l5T, was isolated from a forest soil sample at Dinghu Mountain, Guangdong Province, PR China. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain zong2l5T belongs to the genus Lysobacter, and was most closely related to Lysobacter enzymogenes KCTC 12131T (97.7 %) and Lysobacter soli KCTC 22011T (97.6 %). The novel strain showed an average nucleotide identity (ANI) value of 81.5 % and a digital DNA-DNA hybridization (dDDH) value of 25.3 % with L. enzymogenes KCTC 12131T based on draft genome sequences, followed by L. soli KCTC 22011T with ANI and dDDH values of 79.4 % and 22.7 %, respectively. The DNA G+C content of strain zong2l5T based on the whole genome sequence was 69.2 mol%. The major fatty acids were iso-C15 : 0, iso-C17 : 0 and summed feature 9 (iso-C17 : 1ω9c and/or 10-methyl C16 : 0). Strain zong2l5T contained Q-8 as the major isoprenoid quinone and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidyl-N-methylethanolamine, phosphatidylethanolamine, three unidentified phospholipids and an unidentified aminolipid. The phenotypic, genotypic and chemotaxonomic anlyses clearly showed that strain zong2l5T represents a novel species of the genus Lysobacter, for which the name Lysobactersilvisoli sp. nov. is proposed. The type strain is zong2l5T (=GDMCC 1.1489T=KCTC 52923T).}, } @article {pmid30422104, year = {2018}, author = {Huang, SP and Chen, TY and Chen, JS and Wang, LT and Huang, L and Lin, ST and Wei, CL and Lin, S and Wang, PL and Chen, YM and Shieh, WY}, title = {Dongshaea marina gen. nov., sp. nov., a facultatively anaerobic marine bacterium that ferments glucose with gas production.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003080}, pmid = {30422104}, issn = {1466-5034}, abstract = {Two isolates of heterotrophic, facultatively anaerobic, marine bacteria, designated DM1 and DM2T, were recovered from a lagoon sediment sample of Dongsha Island, Taiwan. Cells were Gram-reaction-negative rods. Nearly all of the cells were non-motile and non-flagellated during the late exponential to early stationary phase of growth, while a few of the cells exhibited motility with monotrichous flagellation. The two isolates required NaCl for growth and grew optimally at about 30 °C, 2-3 % NaCl and pH 7-8. They grew aerobically and could achieve anaerobic growth by fermenting d-glucose or other carbohydrates with production of acids and the gases, including CO2 and H2. Ubiquinone Q-8 was the only respiratory quinone. Cellular fatty acids were predominated by C16 : 0, C18 : 1ω7c and C16 : 1ω7c. The major polar lipid was phosphatidylethanolamine. Strains DM1 and DM2T had DNA G+C contents of 52.0 and 51.8 mol%, respectively, as determined by HPLC analysis. Phylogenetic analyses based on 16S rRNA gene sequences clearly indicated that the two isolates formed a distinct genus-level lineage in the family Aeromonadaceae of the class Gammaproteobacteria and was an outgroup with respect to a stable supragenic clade comprising species of the genera Oceanimonas, Oceanisphaera and Zobellella. The phylogenetic data and those from chemotaxonomic, physiological and morphological characterizations support the establishment of a novel species and genus inside the family Aeromonadaceae, for which the name Dongshaea marina gen. nov., sp. nov. is proposed. The type strain is DM2T (=BCRC 81069T=JCM 32096T).}, } @article {pmid30421850, year = {2018}, author = {de Andrade Cavalcante, D and De-Souza, MT and de Orem, JC and de Magalhães, MIA and Martins, PH and Boone, TJ and Castillo, JA and Driks, A}, title = {Ultrastructural analysis of spores from diverse Bacillales species isolated from Brazilian soil.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12713}, pmid = {30421850}, issn = {1758-2229}, support = {//National Council for Scientific and Technological Development/ ; }, abstract = {Many species in the order Bacillales form a specialized cell type called a spore that is resistant to a range of environmental stresses. Transmission electron microscopy (TEM) reveals that the spore is comprised of a series of concentric shells, surrounding an interior compartment harbouring the spore DNA. The outermost of these shells varies considerably in morphology among species, likely reflecting adaptations to the highly diverse niches in which spores are found. To better characterize the variation in spore ultrastructure among diverse species, we used TEM to analyse spores from a collection of 23 aerobic spore-forming bacteria from the Solo do Distrito Federal (SDF strains), spanning the genera Bacillus, Lysinibacillus, Paenibacillus and Brevibacillus, isolated from soil from central Brazil. We found that the structures of these spores varied widely, as expected. Interestingly, even though these isolates are novel strains of each species, they were structurally very similar to the known examples of each species in the literature. Because in most cases, the species we analysed are poorly characterized, our data provide important evidence regarding which structural features are likely to be constant within a taxon and which are likely to vary.}, } @article {pmid30421788, year = {2019}, author = {Sousa, F and Neiva, J and Martins, N and Jacinto, R and Anderson, L and Raimondi, PT and Serrão, EA and Pearson, GA}, title = {Increased evolutionary rates and conserved transcriptional response following allopolyploidization in brown algae.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {59-72}, doi = {10.1111/evo.13645}, pmid = {30421788}, issn = {1558-5646}, support = {FCT/MEC to CCMAR - UID/Multi/04326/2013//David and Lucile Packard Foundation/ ; //Bureau of Ocean Energy Management, Pew Foundation/ ; PTDC/MAR- EST/6053/2014//Foundation for Science and Technology (FCT) of Portugal/ ; EXPL/BIA-EVF/2263/2013//Foundation for Science and Technology (FCT) of Portugal/ ; Biodiversa/0004/2015//Foundation for Science and Technology (FCT) of Portugal/ ; SFRH/BPD/88935/2012//Foundation for Science and Technology (FCT) of Portugal/ ; SFRH/BPD/122567/2016//Foundation for Science and Technology (FCT) of Portugal/ ; }, abstract = {Genome mergers between independently evolving lineages, via allopolyploidy, can potentially lead to instantaneous sympatric speciation. However, little is known about the consequences of allopolyploidy and the resultant "genome shock" on genome evolution and expression beyond the plant and fungal branches of the Tree of Life. The aim of this study was to compare substitution rates and gene expression patterns in two allopolyploid brown algae (Phaeophyceae and Heterokonta) and their progenitors in the genus Pelvetiopsis N. L. Gardner in the north-east Pacific, and to date their relationships. We used RNA-seq data, all potential orthologues, and putative single-copy loci for phylogenomic, divergence, and gene expression analyses. The multispecies coalescent placed the origin of allopolyploids in the late Pleistocene (0.35-0.05 Ma). Homoeologues displayed increased nonsynonymous divergence compared with parental orthologues, consistent with relaxed selective constraint following allopolyploidization, including for genes with no evidence of pseudogenization or neofunctionalization. Patterns of homoeologue-orthologue expression conservation and expression level dominance were largely shared with both natural plant and fungal allopolyploids. Our results provide further support for common cross-Kingdom patterns of allopolyploid genome evolution and transcriptional responses, here in the evolutionarily distinct marine heterokont brown algae.}, } @article {pmid30421572, year = {2018}, author = {Ebert, MK and Spanner, RE and de Jonge, R and Smith, DJ and Holthusen, J and Secor, GA and Thomma, BPHJ and Bolton, MD}, title = {Gene cluster conservation identifies melanin and perylenequinone biosynthesis pathways in multiple plant pathogenic fungi.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14475}, pmid = {30421572}, issn = {1462-2920}, support = {3060-22000-049//Agricultural Research Service/ ; ALTF 359-2013//European Molecular Biology Organization/ ; 12B8116N//Fonds Wetenschappelijk Onderzoek/ ; 833.13.007//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, abstract = {Perylenequinones are a family of structurally related polyketide fungal toxins with nearly universal toxicity. These photosensitizing compounds absorb light energy which enables them to generate reactive oxygen species that damage host cells. This potent mechanism serves as an effective weapon for plant pathogens in disease or niche establishment. The sugar beet pathogen Cercospora beticola secretes the perylenequinone cercosporin during infection. We have shown recently that the cercosporin toxin biosynthesis (CTB) gene cluster is present in several other phytopathogenic fungi, prompting the search for biosynthetic gene clusters (BGCs) of structurally similar perylenequinones in other fungi. Here, we report the identification of the elsinochrome and phleichrome BGCs of Elsinoë fawcettii and Cladosporium phlei, respectively, based on gene cluster conservation with the CTB and hypocrellin BGCs. Furthermore, we show that previously reported BGCs for elsinochrome and phleichrome are involved in melanin production. Phylogenetic analysis of the corresponding melanin polyketide synthases (PKSs) and alignment of melanin BGCs revealed high conservation between the established and newly identified C. beticola, E. fawcettii and C. phlei melanin BGCs. Mutagenesis of the identified perylenequinone and melanin PKSs in C. beticola and E. fawcettii coupled with mass spectrometric metabolite analyses confirmed their roles in toxin and melanin production.}, } @article {pmid30421557, year = {2019}, author = {Torregrosa-Crespo, J and Pire, C and Martínez-Espinosa, RM and Bergaust, L}, title = {Denitrifying haloarchaea within the genus Haloferax display divergent respiratory phenotypes, with implications for their release of nitrogenous gases.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {427-436}, doi = {10.1111/1462-2920.14474}, pmid = {30421557}, issn = {1462-2920}, support = {ACIF 2016/077//Generalitat Valenciana/ ; CTM2013-43147-R//Ministerio de Economía y Competitividad/ ; 231282//Norges Forskningsråd/ ; 275389//Norges Forskningsråd/ ; }, abstract = {Haloarchaea are extremophiles, generally thriving at high temperatures and salt concentrations, thus, with limited access to oxygen. As a strategy to maintain a respiratory metabolism, many halophilic archaea are capable of denitrification. Among them are members of the genus Haloferax, which are abundant in saline/hypersaline environments. Three reported haloarchaeal denitrifiers, Haloferax mediterranei, Haloferax denitrificans and Haloferax volcanii, were characterized with respect to their denitrification phenotype. A semi-automatic incubation system was used to monitor the depletion of electron acceptors and accumulation of gaseous intermediates in batch cultures under a range of conditions. Out of the species tested, only H. mediterranei was able to consistently reduce all available N-oxyanions to N2 , while the other two released significant amounts of NO and N2 O, which affect tropospheric and stratospheric chemistries respectively. The prevalence and magnitude of hypersaline ecosystems are on the rise due to climate change and anthropogenic activity. Thus, the biology of halophilic denitrifiers is inherently interesting, due to their contribution to the global nitrogen cycle, and potential application in bioremediation. This work is the first detailed physiological study of denitrification in haloarchaea, and as such a seed for our understanding of the drivers of nitrogen turnover in hypersaline systems.}, } @article {pmid30421540, year = {2018}, author = {Lavrov, AI and Bolshakov, FV and Tokina, DB and Ereskovsky, AV}, title = {Sewing up the wounds : The epithelial morphogenesis as a central mechanism of calcaronean sponge regeneration.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {6-7}, pages = {351-371}, doi = {10.1002/jez.b.22830}, pmid = {30421540}, issn = {1552-5015}, support = {16-04-00084//Russian Foundation for Basic Research/ ; 17-14-01089//Russian Science Foundation/ ; ANR-11-LABX-0061//A*MIDEX/ ; //Excellence Initiative of Aix-Marseille University-A*MIDEX/ ; }, abstract = {Sponges (Porifera) demonstrate prominent regeneration abilities and possess a wide variety of mechanisms, used during this process. In the current study, we combined in vivo observations with histological, immunohistochemical, and ultrastructural technics to elucidate the fine cellular mechanisms of the regeneration in the calcareous sponge Leucosolenia cf. variabilis. The regeneration of Leucosolenia cf. variabilis ends within 4-6 days. The crucial step of the process is the formation of the transient regenerative membrane, formed by the epithelial morphogenesis-spreading of the intact exopinacoderm and choanoderm. The spreading of the choanoderm is accompanied by the transdifferentiation of the choanocytes. The regenerative membrane develops without any contribution of the mesohyl cells. Subsequently, the membrane gradually transforms into the body wall. The cell proliferation is neither affected nor contributes to the regeneration at any stage. Thus, Leucosolenia cf. variabilis regeneration relies on the remodeling of the intact tissues through the epithelial morphogenesis, accompanied by the transdifferentiation of some differentiated cell types, which makes it similar to the regeneration in homoscleromorphs and eumetazoans.}, } @article {pmid30421490, year = {2019}, author = {Biessy, A and Novinscak, A and Blom, J and Léger, G and Thomashow, LS and Cazorla, FM and Josic, D and Filion, M}, title = {Diversity of phytobeneficial traits revealed by whole-genome analysis of worldwide-isolated phenazine-producing Pseudomonas spp.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {437-455}, doi = {10.1111/1462-2920.14476}, pmid = {30421490}, issn = {1462-2920}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; //New Brunswick Innovation Foundation/ ; }, abstract = {Plant-beneficial Pseudomonas spp. competitively colonize the rhizosphere and display plant-growth promotion and/or disease-suppression activities. Some strains within the P. fluorescens species complex produce phenazine derivatives, such as phenazine-1-carboxylic acid. These antimicrobial compounds are broadly inhibitory to numerous soil-dwelling plant pathogens and play a role in the ecological competence of phenazine-producing Pseudomonas spp. We assembled a collection encompassing 63 strains representative of the worldwide diversity of plant-beneficial phenazine-producing Pseudomonas spp. In this study, we report the sequencing of 58 complete genomes using PacBio RS II sequencing technology. Distributed among four subgroups within the P. fluorescens species complex, the diversity of our collection is reflected by the large pangenome which accounts for 25 413 protein-coding genes. We identified genes and clusters encoding for numerous phytobeneficial traits, including antibiotics, siderophores and cyclic lipopeptides biosynthesis, some of which were previously unknown in these microorganisms. Finally, we gained insight into the evolutionary history of the phenazine biosynthetic operon. Given its diverse genomic context, it is likely that this operon was relocated several times during Pseudomonas evolution. Our findings acknowledge the tremendous diversity of plant-beneficial phenazine-producing Pseudomonas spp., paving the way for comparative analyses to identify new genetic determinants involved in biocontrol, plant-growth promotion and rhizosphere competence.}, } @article {pmid30421486, year = {2019}, author = {Zhou, S and Zhang, P and Zhou, H and Liu, X and Li, SM and Guo, L and Li, K and Yin, WB}, title = {A new regulator RsdA mediating fungal secondary metabolism has a detrimental impact on asexual development in Pestalotiopsis fici.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {416-426}, doi = {10.1111/1462-2920.14473}, pmid = {30421486}, issn = {1462-2920}, support = {2016YFD0400105//National Key Research and Development Program/ ; 31700070//National Natural Science Foundation of China/ ; [2017]6052//Project Based Personnel Exchange Program/ ; }, abstract = {Secondary metabolite (SM) production and development are correlated processes in fungi that are often coordinated by pleiotropic regulators. The eukaryotic regulators are critical players in mediating SM production related to fungal development, yet little data are available to support this hypothesis. In this study, a global regulator, RsdA (regulation of secondary metabolism and development), was identified through genome-wide analysis and deletion of the regulator gene in the endophytic fungus Pestalotiopsis fici. Here, we established that RsdA regulation of SMs is accompanied by the repression of asexual development. Deletion of rsdA significantly reduces not only asexual development, resulting in low sporulation and abnormal conidia, but also the major SM production, while remarkably increasing the melanin production. Overproduction of melanin leads to the formation of unusual, heavily pigmented hyphae. Transcriptome analysis data provide the evidence that RsdA globally regulates genes involved in secondary metabolism and asexual development. Double deletion of rsdA and the melanin polyketide synthase gene PfmaE confirm that RsdA regulation of asexual development is independent of the melanin biosynthetic pathway. Finally, our results demonstrate that RsdA can be used for the discovery of secondary metabolites in filamentous fungi.}, } @article {pmid30421480, year = {2019}, author = {Schweizer, M and Warmuth, V and Alaei Kakhki, N and Aliabadian, M and Förschler, M and Shirihai, H and Suh, A and Burri, R}, title = {Parallel plumage colour evolution and introgressive hybridization in wheatears.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {100-110}, doi = {10.1111/jeb.13401}, pmid = {30421480}, issn = {1420-9101}, support = {2015-R14//Science of Life Laboratory Swedish Biodiversity Program/ ; 32567.3//Ferdowsi University of Mashhad/ ; 96010126//Iranian National Science Foundation/ ; //Ministry of Science, Research and Technology of the Islamic Republic of Iran/ ; }, abstract = {Genetic and phenotypic mosaics, in which various phenotypes and different genomic regions show discordant patterns of species or population divergence, offer unique opportunities to study the role of ancestral and introgressed genetic variation in phenotypic evolution. Here, we investigated the evolution of discordant phenotypic and genetic divergence in a monophyletic clade of four songbird taxa-pied wheatear (O. pleschanka), Cyprus wheatear (Oenanthe cypriaca), and western and eastern subspecies of black-eared wheatear (O. h. hispanica and O. h. melanoleuca). Phenotypically, black back and neck sides distinguish pied and Cyprus wheatears from the white-backed/necked black-eared wheatears. Meanwhile, mitochondrial variation only distinguishes western black-eared wheatear. In the absence of nuclear genetic data, and given frequent hybridization among eastern black-eared and pied wheatear, it remains unclear whether introgression is responsible for discordance between mitochondrial divergence patterns and phenotypic similarities, or whether plumage coloration evolved in parallel. Multispecies coalescent analyses of about 20,000 SNPs obtained from RAD data mapped to a draft genome assembly resolve the species tree, provide evidence for the parallel evolution of colour phenotypes and establish western and eastern black-eared wheatears as independent taxa that should be recognized as full species. The presence of the entire admixture spectrum in the Iranian hybrid zone and the detection of footprints of introgression from pied into eastern black-eared wheatear beyond the hybrid zone despite strong geographic structure of ancestry proportions furthermore suggest a potential role for introgression in parallel plumage colour evolution. Our results support the importance of standing heterospecific and/or ancestral variation in phenotypic evolution.}, } @article {pmid30421421, year = {2019}, author = {Patten, MM}, title = {The X chromosome favors males under sexually antagonistic selection.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {84-91}, doi = {10.1111/evo.13646}, pmid = {30421421}, issn = {1558-5646}, abstract = {The X chromosome is found twice as often in females as males. This has led to an intuition that X-linked genes for traits experiencing sexually antagonistic selection should tend to evolve toward the female optimum. However, this intuition has never been formally examined. In this paper, I present a simple mathematical model and ask whether the X chromosome is indeed biased toward effecting female-optimal phenotypes. Counter to the intuition, I find that the exact opposite bias exists; the X chromosome is revealed to be a welcome spot for mutations that benefit males at the expense of females. Not only do male-beneficial alleles have an easier time of invading and spreading through a population, but they also achieve higher equilibrium frequencies than comparable female-beneficial alleles. The X chromosome is therefore expected over evolutionary time to nudge phenotypes closer to the male optimum. Consequently, the X chromosome should find itself engaged in perpetual intragenomic conflicts with the autosomes and the mitochondria over developmental outcomes. The X chromosome's male bias and the intragenomic conflicts that ensue bear on the evolution of gene regulation, speciation, and our concept of organismality.}, } @article {pmid30421418, year = {2018}, author = {Gomes, ACR and Cardoso, GC}, title = {Choice of high-quality mates versus avoidance of low-quality mates.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2608-2616}, doi = {10.1111/evo.13630}, pmid = {30421418}, issn = {1558-5646}, support = {PTDC/BIA-EVF/4852/2014//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/129002/2017//Fundação para a Ciência e a Tecnologia/ ; SFRH/BPD/110165/2015//Fundação para a Ciência e a Tecnologia/ ; }, abstract = {Research in sexual selection assumes that individuals attempt to choose high-quality mates, and that sexual signals evolve to indicate high quality. But it may often be more important to instead discriminate and avoid low-quality mates, thus reducing the likelihood of large penalties in fitness. We show, using simulations, that avoidance of low-quality mates (i.e., rejecting low-quality and accepting either high- or medium-quality mates) evolves in socio-ecological circumstances such as monogamy with moderate opportunities for choice, costly choice, or abundant low-quality mates. We also show that this strategy is qualitatively different from choosing high-quality mates (i.e., preferring high-quality over medium- and low-quality mates). Rather than selecting signals that distinguish high- from low- and medium-quality mates, avoiding low-quality mates selects for signals or cues attuned at discriminating low-quality mates from the remaining (e.g., low-cost signals, absence of signaling mistakes). This may help explain the high diversity of sexual signals in nature, and their high evolutionary turnover with frequent losses and replacements (rather than reductions/increases of the same signal) over evolutionary time.}, } @article {pmid30421144, year = {2019}, author = {Brun, P and Bernabè, G and Filippini, R and Piovan, A}, title = {In Vitro Antimicrobial Activities of Commercially Available Tea Tree (Melaleuca alternifolia) Essential Oils.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {108-116}, doi = {10.1007/s00284-018-1594-x}, pmid = {30421144}, issn = {1432-0991}, abstract = {Melaleuca alternifolia tea tree oil (TTO) is largely used in cutaneous infections. Clinical observations reported antibacterial, antifungal, and antiviral activities, whereas in vitro experiments ascribed most of biological properties to terpinen-4-ol. Since different plant chemotypes and storage conditions result in variations of chemical composition of commercially available TTO, in this study we investigated the antimicrobial activity and the chemical profile of ten commercially available TTO products. The antimicrobial activity was assessed against Candida glabrata, Herpes simplex virus type 1 (HSV-1), methicillin-resistant Staphylococcus aureus (MRSA), and Pseudomonas aeruginosa grown in planktonic mode or biofilms. Only five out of ten TTO batches reported significant antimicrobial activity. The identified TTO products reduced bacterial survival in biofilms, generated oxidative damage in C. glabrata, and diminished HSV-1 infectivity. GC-MS analysis revealed that all the analyzed TTO batches fitted into the terpinen-4-ol chemotype even if we reported great variability in composition of nine major ISO-specified TTO components. Overall, we were not able to ascribe the antimicrobial activity to the content in terpinen-4-ol. We therefore conclude that the antimicrobial activity of TTO results from complex interaction among different components.}, } @article {pmid30421143, year = {2019}, author = {Wang, K and Liu, XF and Bu, QT and Zheng, Y and Chen, XA and Li, YQ and Mao, XM}, title = {Transcriptome-Based Identification of a Strong Promoter for Hyper-production of Natamycin in Streptomyces.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {95-99}, doi = {10.1007/s00284-018-1589-7}, pmid = {30421143}, issn = {1432-0991}, support = {2016YFD0400805//National Key Research and Development Program/ ; 31571284//National Natural Science Foundation of China/ ; 31470212//National Natural Science Foundation of China/ ; 31520103901//National Natural Science Foundation of China/ ; }, abstract = {Streptomyces are famed producers of secondary metabolites with diverse bioactivities and structures. However, biosynthesis of natural products will consume vast precursors from primary metabolism, and some secondary metabolites are toxic to the hosts. To overcome this circumstance and over-produce secondary metabolites, one of the strategies is to over-express biosynthetic genes under strong promoters specifically expressed during secondary metabolism. For this purpose, here based on Microarray and eGFP reporter assays, we obtained a promoter thlM4p, whose activity was undetectable in the first 2 days of fermentation, but sevenfold higher than the strong promoter ermE*p in the following days. Moreover, when the positive regulator gene scnRII was driven from thlM4p, natamycin yield increased 30% compared to ermE*p. Therefore, we provide a new way to identify promoters, which is silenced during primary metabolism while strongly expressed under secondary metabolism of Streptomyces.}, } @article {pmid30420785, year = {2019}, author = {Beerli, C and Yakimovich, A and Kilcher, S and Reynoso, GV and Fläschner, G and Müller, DJ and Hickman, HD and Mercer, J}, title = {Vaccinia virus hijacks EGFR signalling to enhance virus spread through rapid and directed infected cell motility.}, journal = {Nature microbiology}, volume = {4}, number = {2}, pages = {216-225}, doi = {10.1038/s41564-018-0288-2}, pmid = {30420785}, issn = {2058-5276}, abstract = {Cell motility is essential for viral dissemination1. Vaccinia virus (VACV), a close relative of smallpox virus, is thought to exploit cell motility as a means to enhance the spread of infection1. A single viral protein, F11L, contributes to this by blocking RhoA signalling to facilitate cell retraction2. However, F11L alone is not sufficient for VACV-induced cell motility, indicating that additional viral factors must be involved. Here, we show that the VACV epidermal growth factor homologue, VGF, promotes infected cell motility and the spread of viral infection. We found that VGF secreted from early infected cells is cleaved by ADAM10, after which it acts largely in a paracrine manner to direct cell motility at the leading edge of infection. Real-time tracking of cells infected in the presence of EGFR, MAPK, FAK and ADAM10 inhibitors or with VGF-deleted and F11-deleted viruses revealed defects in radial velocity and directional migration efficiency, leading to impaired cell-to-cell spread of infection. Furthermore, intravital imaging showed that virus spread and lesion formation are attenuated in the absence of VGF. Our results demonstrate how poxviruses hijack epidermal growth factor receptor-induced cell motility to promote rapid and efficient spread of infection in vitro and in vivo.}, } @article {pmid30420784, year = {2019}, author = {Full, F and van Gent, M and Sparrer, KMJ and Chiang, C and Zurenski, MA and Scherer, M and Brockmeyer, NH and Heinzerling, L and Stürzl, M and Korn, K and Stamminger, T and Ensser, A and Gack, MU}, title = {Centrosomal protein TRIM43 restricts herpesvirus infection by regulating nuclear lamina integrity.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {164-176}, pmid = {30420784}, issn = {2058-5276}, support = {R01 AI087846/AI/NIAID NIH HHS/United States ; R01 AI127774/AI/NIAID NIH HHS/United States ; R21 AI118509/AI/NIAID NIH HHS/United States ; T32 GM007183/GM/NIGMS NIH HHS/United States ; }, abstract = {Tripartite motif (TRIM) proteins mediate antiviral host defences by either directly targeting viral components or modulating innate immune responses. Here we identify a mechanism of antiviral restriction in which a TRIM E3 ligase controls viral replication by regulating the structure of host cell centrosomes and thereby nuclear lamina integrity. Through RNAi screening we identified several TRIM proteins, including TRIM43, that control the reactivation of Kaposi's sarcoma-associated herpesvirus. TRIM43 was distinguished by its ability to restrict a broad range of herpesviruses and its profound upregulation during herpesvirus infection as part of a germline-specific transcriptional program mediated by the transcription factor DUX4. TRIM43 ubiquitinates the centrosomal protein pericentrin, thereby targeting it for proteasomal degradation, which subsequently leads to alterations of the nuclear lamina that repress active viral chromatin states. Our study identifies a role of the TRIM43-pericentrin-lamin axis in intrinsic immunity, which may be targeted for therapeutic intervention against herpesviral infections.}, } @article {pmid30420783, year = {2019}, author = {Cheng, AZ and Yockteng-Melgar, J and Jarvis, MC and Malik-Soni, N and Borozan, I and Carpenter, MA and McCann, JL and Ebrahimi, D and Shaban, NM and Marcon, E and Greenblatt, J and Brown, WL and Frappier, L and Harris, RS}, title = {Epstein-Barr virus BORF2 inhibits cellular APOBEC3B to preserve viral genome integrity.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {78-88}, pmid = {30420783}, issn = {2058-5276}, support = {F30 CA200432/CA/NCI NIH HHS/United States ; R21 CA206309/CA/NCI NIH HHS/United States ; T32 CA009138/CA/NCI NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; T32 GM008244/GM/NIGMS NIH HHS/United States ; }, abstract = {The apolipoprotein B messenger RNA editing enzyme, catalytic polypeptide-like (APOBEC) family of single-stranded DNA (ssDNA) cytosine deaminases provides innate immunity against virus and transposon replication1-4. A well-studied mechanism is APOBEC3G restriction of human immunodeficiency virus type 1, which is counteracted by a virus-encoded degradation mechanism1-4. Accordingly, most work has focused on retroviruses with obligate ssDNA replication intermediates and it is unclear whether large double-stranded DNA (dsDNA) viruses may be similarly susceptible to restriction. Here, we show that the large dsDNA herpesvirus Epstein-Barr virus (EBV), which is the causative agent of infectious mononucleosis and multiple cancers5, utilizes a two-pronged approach to counteract restriction by APOBEC3B. Proteomics studies and immunoprecipitation experiments showed that the ribonucleotide reductase large subunit of EBV, BORF26,7, binds APOBEC3B. Mutagenesis mapped the interaction to the APOBEC3B catalytic domain, and biochemical studies demonstrated that BORF2 stoichiometrically inhibits APOBEC3B DNA cytosine deaminase activity. BORF2 also caused a dramatic relocalization of nuclear APOBEC3B to perinuclear bodies. On lytic reactivation, BORF2-null viruses were susceptible to APOBEC3B-mediated deamination as evidenced by lower viral titres, lower infectivity and hypermutation. The Kaposi's sarcoma-associated herpesvirus homologue, ORF61, also bound APOBEC3B and mediated relocalization. These data support a model where the genomic integrity of human γ-herpesviruses is maintained by active neutralization of the antiviral enzyme APOBEC3B.}, } @article {pmid30420782, year = {2019}, author = {Subramanian, K and Neill, DR and Malak, HA and Spelmink, L and Khandaker, S and Dalla Libera Marchiori, G and Dearing, E and Kirby, A and Yang, M and Achour, A and Nilvebrant, J and Nygren, PÅ and Plant, L and Kadioglu, A and Henriques-Normark, B}, title = {Pneumolysin binds to the mannose receptor C type 1 (MRC-1) leading to anti-inflammatory responses and enhanced pneumococcal survival.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {62-70}, doi = {10.1038/s41564-018-0280-x}, pmid = {30420782}, issn = {2058-5276}, abstract = {Streptococcus pneumoniae (the pneumococcus) is a major cause of mortality and morbidity globally, and the leading cause of death in children under 5 years old. The pneumococcal cytolysin pneumolysin (PLY) is a major virulence determinant known to induce pore-dependent pro-inflammatory responses. These inflammatory responses are driven by PLY-host cell membrane cholesterol interactions, but binding to a host cell receptor has not been previously demonstrated. Here, we discovered a receptor for PLY, whereby pro-inflammatory cytokine responses and Toll-like receptor signalling are inhibited following PLY binding to the mannose receptor C type 1 (MRC-1) in human dendritic cells and mouse alveolar macrophages. The cytokine suppressor SOCS1 is also upregulated. Moreover, PLY-MRC-1 interactions mediate pneumococcal internalization into non-lysosomal compartments and polarize naive T cells into an interferon-γlow, interleukin-4high and FoxP3+ immunoregulatory phenotype. In mice, PLY-expressing pneumococci colocalize with MRC-1 in alveolar macrophages, induce lower pro-inflammatory cytokine responses and reduce neutrophil infiltration compared with a PLY mutant. In vivo, reduced bacterial loads occur in the airways of MRC-1-deficient mice and in mice in which MRC-1 is inhibited using blocking antibodies. In conclusion, we show that pneumococci use PLY-MRC-1 interactions to downregulate inflammation and enhance bacterial survival in the airways. These findings have important implications for future vaccine design.}, } @article {pmid30420781, year = {2019}, author = {Gan, N and Nakayasu, ES and Hollenbeck, PJ and Luo, ZQ}, title = {Legionella pneumophila inhibits immune signalling via MavC-mediated transglutaminase-induced ubiquitination of UBE2N.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {134-143}, pmid = {30420781}, issn = {2058-5276}, support = {P41 GM103493/GM/NIGMS NIH HHS/United States ; R01 AI127465/AI/NIAID NIH HHS/United States ; R21 AI117205/AI/NIAID NIH HHS/United States ; }, abstract = {The bacterial pathogen Legionella pneumophila modulates host immunity using effectors translocated by its Dot/Icm transporter to facilitate its intracellular replication. A number of these effectors employ diverse mechanisms to interfere with protein ubiquitination, a post-translational modification essential for immunity. Here, we have found that L. pneumophila induces monoubiquitination of the E2 enzyme UBE2N by its Dot/Icm substrate MavC(Lpg2147). We demonstrate that MavC is a transglutaminase that catalyses covalent linkage of ubiquitin to Lys92 and Lys94 of UBE2N via Gln40. Similar to canonical transglutaminases, MavC possess deamidase activity that targets ubiquitin at Gln40. We identified Cys74 as the catalytic residue for both ubiquitination and deamidation activities. Furthermore, ubiquitination of UBE2N by MavC abolishes its activity in the formation of K63-type polyubiquitin chains, which dampens NF-κB signalling in the initial phase of bacterial infection. Our results reveal an unprecedented mechanism of modulating host immunity by modifying a key ubiquitination enzyme by ubiquitin transglutamination.}, } @article {pmid30420747, year = {2018}, author = {Navarro, A and López-Bao, JV}, title = {Towards a greener Common Agricultural Policy.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1830-1833}, doi = {10.1038/s41559-018-0724-y}, pmid = {30420747}, issn = {2397-334X}, } @article {pmid30420746, year = {2018}, author = {Murat, C and Payen, T and Noel, B and Kuo, A and Morin, E and Chen, J and Kohler, A and Krizsán, K and Balestrini, R and Da Silva, C and Montanini, B and Hainaut, M and Levati, E and Barry, KW and Belfiori, B and Cichocki, N and Clum, A and Dockter, RB and Fauchery, L and Guy, J and Iotti, M and Le Tacon, F and Lindquist, EA and Lipzen, A and Malagnac, F and Mello, A and Molinier, V and Miyauchi, S and Poulain, J and Riccioni, C and Rubini, A and Sitrit, Y and Splivallo, R and Traeger, S and Wang, M and Žifčáková, L and Wipf, D and Zambonelli, A and Paolocci, F and Nowrousian, M and Ottonello, S and Baldrian, P and Spatafora, JW and Henrissat, B and Nagy, LG and Aury, JM and Wincker, P and Grigoriev, IV and Bonfante, P and Martin, FM}, title = {Pezizomycetes genomes reveal the molecular basis of ectomycorrhizal truffle lifestyle.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1956-1965}, doi = {10.1038/s41559-018-0710-4}, pmid = {30420746}, issn = {2397-334X}, abstract = {Tuberaceae is one of the most diverse lineages of symbiotic truffle-forming fungi. To understand the molecular underpinning of the ectomycorrhizal truffle lifestyle, we compared the genomes of Piedmont white truffle (Tuber magnatum), Périgord black truffle (Tuber melanosporum), Burgundy truffle (Tuber aestivum), pig truffle (Choiromyces venosus) and desert truffle (Terfezia boudieri) to saprotrophic Pezizomycetes. Reconstructed gene duplication/loss histories along a time-calibrated phylogeny of Ascomycetes revealed that Tuberaceae-specific traits may be related to a higher gene diversification rate. Genomic features in Tuber species appear to be very similar, with high transposon content, few genes coding lignocellulose-degrading enzymes, a substantial set of lineage-specific fruiting-body-upregulated genes and high expression of genes involved in volatile organic compound metabolism. Developmental and metabolic pathways expressed in ectomycorrhizae and fruiting bodies of T. magnatum and T. melanosporum are unexpectedly very similar, owing to the fact that they diverged ~100 Ma. Volatile organic compounds from pungent truffle odours are not the products of Tuber-specific gene innovations, but rely on the differential expression of an existing gene repertoire. These genomic resources will help to address fundamental questions in the evolution of the truffle lifestyle and the ecology of fungi that have been praised as food delicacies for centuries.}, } @article {pmid30420745, year = {2018}, author = {Huang, K and Xia, J and Wang, Y and Ahlström, A and Chen, J and Cook, RB and Cui, E and Fang, Y and Fisher, JB and Huntzinger, DN and Li, Z and Michalak, AM and Qiao, Y and Schaefer, K and Schwalm, C and Wang, J and Wei, Y and Xu, X and Yan, L and Bian, C and Luo, Y}, title = {Enhanced peak growth of global vegetation and its key mechanisms.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1897-1905}, doi = {10.1038/s41559-018-0714-0}, pmid = {30420745}, issn = {2397-334X}, abstract = {The annual peak growth of vegetation is critical in characterizing the capacity of terrestrial ecosystem productivity and shaping the seasonality of atmospheric CO2 concentrations. The recent greening of global lands suggests an increasing trend of terrestrial vegetation growth, but whether or not the peak growth has been globally enhanced still remains unclear. Here, we use two global datasets of gross primary productivity (GPP) and a satellite-derived Normalized Difference Vegetation Index (NDVI) to characterize recent changes in annual peak vegetation growth (that is, GPPmax and NDVImax). We demonstrate that the peak in the growth of global vegetation has been linearly increasing during the past three decades. About 65% of the NDVImax variation is evenly explained by expanding croplands (21%), rising CO2 (22%) and intensifying nitrogen deposition (22%). The contribution of expanding croplands to the peak growth trend is substantiated by measurements from eddy-flux towers, sun-induced chlorophyll fluorescence and a global database of plant traits, all of which demonstrate that croplands have a higher photosynthetic capacity than other vegetation types. The large contribution of CO2 is also supported by a meta-analysis of 466 manipulative experiments and 15 terrestrial biosphere models. Furthermore, we show that the contribution of GPPmax to the change in annual GPP is less in the tropics than in other regions. These multiple lines of evidence reveal an increasing trend in the peak growth of global vegetation. The findings highlight the important roles of agricultural intensification and atmospheric changes in reshaping the seasonality of global vegetation growth.}, } @article {pmid30420744, year = {2018}, author = {Vicca, S}, title = {Global vegetation's CO2 uptake.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1840-1841}, doi = {10.1038/s41559-018-0730-0}, pmid = {30420744}, issn = {2397-334X}, } @article {pmid30420743, year = {2019}, author = {Robinson, JPW and Wilson, SK and Robinson, J and Gerry, C and Lucas, J and Assan, C and Govinden, R and Jennings, S and Graham, NAJ}, title = {Productive instability of coral reef fisheries after climate-driven regime shifts.}, journal = {Nature ecology & evolution}, volume = {3}, number = {2}, pages = {183-190}, doi = {10.1038/s41559-018-0715-z}, pmid = {30420743}, issn = {2397-334X}, abstract = {Tropical coastal communities are highly reliant on coral reefs, which provide nutrition and employment for millions of people. Climate-driven coral bleaching events are fundamentally changing coral reef ecosystems and are predicted to reduce productivity of coral reef fish and fisheries, with significant implications for food security and livelihoods. Yet evidence of long-term bleaching impacts on coral reef fishery productivity is lacking. Here, we analyse over 20 years of fish abundance, catch and habitat data to assess long-term impacts of climate-driven coral mass mortality and regime shifts on nearshore artisanal coral reef fisheries in the Seychelles. Contrary to expectations, total catch and mean catch rates were maintained or increased after coral bleaching, consistent with increasing abundance of herbivorous target species in underwater surveys, particularly on macroalgal-dominated reefs. Catch instability increased as habitats followed divergent post-disturbance trajectories and the distribution of target species became more spatially variable, potentially impacting fisher incomes and local market supply chains. Although coral bleaching increased fishery dependence on herbivore species, our results show that climate-impacted reefs can still provide livelihoods and fish protein for coastal communities.}, } @article {pmid30420697, year = {2018}, author = {Morken, JP}, title = {Practically simple reactions convert hydrocarbons to precious chemicals.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {336-337}, doi = {10.1038/d41586-018-07333-w}, pmid = {30420697}, issn = {1476-4687}, mesh = {*Alkenes ; Catalysis ; *Hydrocarbons ; }, } @article {pmid30420696, year = {2018}, author = {Turner, J}, title = {Why I became a mental-health first-aider at my research institute.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {433}, doi = {10.1038/d41586-018-07358-1}, pmid = {30420696}, issn = {1476-4687}, } @article {pmid30420650, year = {2018}, author = {Li, H and Courtois, ET and Sengupta, D and Tan, Y and Chen, KH and Goh, JJL and Kong, SL and Chua, C and Hon, LK and Tan, WS and Wong, M and Cima, I and Tan, MH and Wee, LJK and Hillmer, AM and Tan, IB and Robson, P and Prabhakar, S}, title = {Author Correction: Reference component analysis of single-cell transcriptomes elucidates cellular heterogeneity in human colorectal tumors.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1754}, doi = {10.1038/s41588-018-0299-1}, pmid = {30420650}, issn = {1546-1718}, abstract = {In the version of the article published, the author list is not accurate. Igor Cima and Min-Han Tan should have been authors, appearing after Mark Wong in the author list, while Paul Jongjoon Choi should not have been listed as an author. Igor Cima and Min-Han Tan both have the affiliation Institute of Bioengineering and Nanotechnology, Singapore, Singapore, and their contributions should have been noted in the Author Contributions section as "I.C. preprocessed Primary Cell Atlas data with inputs from M.-H.T." The following description of the contribution of Paul Jongjoon Choi should not have appeared: "P.J.C. supported the smFISH experiments." In the 'RCA: global panel' section of the Online Methods, the following sentence should have appeared as the second sentence, "An expression atlas of human primary cells (the Primary Cell Atlas) was preprocessed similarly to in ref. 55," with new reference 55 (Cima, I. et al. Tumor-derived circulating endothelial cell clusters in colorectal cancer. Science Transl. Med. 8, 345ra89, 2016).}, } @article {pmid30420649, year = {2019}, author = {Assi, SA and Imperato, MR and Coleman, DJL and Pickin, A and Potluri, S and Ptasinska, A and Chin, PS and Blair, H and Cauchy, P and James, SR and Zacarias-Cabeza, J and Gilding, LN and Beggs, A and Clokie, S and Loke, JC and Jenkin, P and Uddin, A and Delwel, R and Richards, SJ and Raghavan, M and Griffiths, MJ and Heidenreich, O and Cockerill, PN and Bonifer, C}, title = {Subtype-specific regulatory network rewiring in acute myeloid leukemia.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {151-162}, doi = {10.1038/s41588-018-0270-1}, pmid = {30420649}, issn = {1546-1718}, abstract = {Acute myeloid leukemia (AML) is a heterogeneous disease caused by a variety of alterations in transcription factors, epigenetic regulators and signaling molecules. To determine how different mutant regulators establish AML subtype-specific transcriptional networks, we performed a comprehensive global analysis of cis-regulatory element activity and interaction, transcription factor occupancy and gene expression patterns in purified leukemic blast cells. Here, we focused on specific subgroups of subjects carrying mutations in genes encoding transcription factors (RUNX1, CEBPα), signaling molecules (FTL3-ITD, RAS) and the nuclear protein NPM1). Integrated analysis of these data demonstrates that each mutant regulator establishes a specific transcriptional and signaling network unrelated to that seen in normal cells, sustaining the expression of unique sets of genes required for AML growth and maintenance.}, } @article {pmid30420648, year = {2018}, author = {Zhang, X and Jia, S and Chen, Z and Chong, YL and Xie, H and Feng, D and Wu, X and Song, DZ and Roy, S and Zhao, C}, title = {Cilia-driven cerebrospinal fluid flow directs expression of urotensin neuropeptides to straighten the vertebrate body axis.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1666-1673}, doi = {10.1038/s41588-018-0260-3}, pmid = {30420648}, issn = {1546-1718}, abstract = {Straightening of the body axis is a major morphogenetic event that produces the typical head-to-tail shape of the vertebrate embryo. Defects in axial straightening can lead to debilitating disorders such as idiopathic scoliosis, characterized by three-dimensional curvatures of the spine1. Although abnormal cerebrospinal fluid (CSF) flow has been implicated in the development of idiopathic scoliosis2, the molecular mechanisms operating downstream of CSF flow remain obscure. Here we show that, in zebrafish embryos, cilia-driven CSF flow transports adrenergic signals that induce urotensin neuropeptides in CSF-contacting neurons along the spinal cord. Urotensins activate their receptor on slow-twitch muscle fibers of the dorsal somite; the contraction of these fibers likely results in straightening of the body axis. Consistent with this, mutation of the urotensin receptor resulted in severe scoliosis in adult zebrafish, closely mimicking the human disorder. These findings suggest that disruption of urotensin signaling by impaired CSF flow could be a critical etiological factor underlying the pathology of idiopathic scoliosis.}, } @article {pmid30420647, year = {2019}, author = {Milner, SG and Jost, M and Taketa, S and Mazón, ER and Himmelbach, A and Oppermann, M and Weise, S and Knüpffer, H and Basterrechea, M and König, P and Schüler, D and Sharma, R and Pasam, RK and Rutten, T and Guo, G and Xu, D and Zhang, J and Herren, G and Müller, T and Krattinger, SG and Keller, B and Jiang, Y and González, MY and Zhao, Y and Habekuß, A and Färber, S and Ordon, F and Lange, M and Börner, A and Graner, A and Reif, JC and Scholz, U and Mascher, M and Stein, N}, title = {Genebank genomics highlights the diversity of a global barley collection.}, journal = {Nature genetics}, volume = {51}, number = {2}, pages = {319-326}, doi = {10.1038/s41588-018-0266-x}, pmid = {30420647}, issn = {1546-1718}, abstract = {Genebanks hold comprehensive collections of cultivars, landraces and crop wild relatives of all major food crops, but their detailed characterization has so far been limited to sparse core sets. The analysis of genome-wide genotyping-by-sequencing data for almost all barley accessions of the German ex situ genebank provides insights into the global population structure of domesticated barley and points out redundancies and coverage gaps in one of the world's major genebanks. Our large sample size and dense marker data afford great power for genome-wide association scans. We detect known and novel loci underlying morphological traits differentiating barley genepools, find evidence for convergent selection for barbless awns in barley and rice and show that a major-effect resistance locus conferring resistance to bymovirus infection has been favored by traditional farmers. This study outlines future directions for genomics-assisted genebank management and the utilization of germplasm collections for linking natural variation to human selection during crop evolution.}, } @article {pmid30420607, year = {2018}, author = {Martyn, I and Kanno, TY and Ruzo, A and Siggia, ED and Brivanlou, AH}, title = {Author Correction: Self-organization of a human organizer by combined Wnt and Nodal signalling.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {E10}, doi = {10.1038/s41586-018-0583-3}, pmid = {30420607}, issn = {1476-4687}, abstract = {Ref. 7 from Benvenisty and colleagues was inadvertently omitted; this has now been cited in the text and added to the reference list, and subsequent references have been renumbered. The Letter has been corrected online.}, } @article {pmid30420606, year = {2018}, author = {Keul, ND and Oruganty, K and Schaper Bergman, ET and Beattie, NR and McDonald, WE and Kadirvelraj, R and Gross, ML and Phillips, RS and Harvey, SC and Wood, ZA}, title = {The entropic force generated by intrinsically disordered segments tunes protein function.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {584-588}, doi = {10.1038/s41586-018-0699-5}, pmid = {30420606}, issn = {1476-4687}, support = {P41 GM103422/GM/NIGMS NIH HHS/United States ; R01 GM114298/GM/NIGMS NIH HHS/United States ; }, abstract = {Protein structures are dynamic and can explore a large conformational landscape1,2. Only some of these structural substates are important for protein function (such as ligand binding, catalysis and regulation)3-5. How evolution shapes the structural ensemble to optimize a specific function is poorly understood3,4. One of the constraints on the evolution of proteins is the stability of the folded 'native' state. Despite this, 44% of the human proteome contains intrinsically disordered peptide segments greater than 30 residues in length6, the majority of which have no known function7-9. Here we show that the entropic force produced by an intrinsically disordered carboxy terminus (ID-tail) shifts the conformational ensemble of human UDP-α-D-glucose-6-dehydrogenase (UGDH) towards a substate with a high affinity for an allosteric inhibitor. The function of the ID-tail does not depend on its sequence or chemical composition. Instead, the affinity enhancement can be accurately predicted based on the length of the intrinsically disordered segment, and is consistent with the entropic force generated by an unstructured peptide attached to the protein surface10-13. Our data show that the unfolded state of the ID-tail rectifies the dynamics and structure of UGDH to favour inhibitor binding. Because this entropic rectifier does not have any sequence or structural constraints, it is an easily acquired adaptation. This model implies that evolution selects for disordered segments to tune the energy landscape of proteins, which may explain the persistence of intrinsic disorder in the proteome.}, } @article {pmid30420555, year = {2018}, author = {Joutsen, J and Sistonen, L}, title = {Tailoring of Proteostasis Networks with Heat Shock Factors.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a034066}, pmid = {30420555}, issn = {1943-0264}, abstract = {Heat shock factors (HSFs) are the main transcriptional regulators of the heat shock response and indispensable for maintaining cellular proteostasis. HSFs mediate their protective functions through diverse genetic programs, which are composed of genes encoding molecular chaperones and other genes crucial for cell survival. The mechanisms that are used to tailor HSF-driven proteostasis networks are not yet completely understood, but they likely comprise from distinct combinations of both genetic and proteomic determinants. In this review, we highlight the versatile HSF-mediated cellular functions that extend from cellular stress responses to various physiological and pathological processes, and we underline the key advancements that have been achieved in the field of HSF research during the last decade.}, } @article {pmid30420518, year = {2018}, author = {Uchiyama, R and Kupkova, K and Shetty, SJ and Linford, AS and Pray-Grant, MG and Wagar, LE and Davis, MM and Haque, R and Gaultier, A and Mayo, MW and Grant, PA and Petri, WA and Bekiranov, S and Auble, DT}, title = {Histone H3 lysine 4 methylation signature associated with human undernutrition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11264-E11273}, pmid = {30420518}, issn = {1091-6490}, support = {R01 AI043596/AI/NIAID NIH HHS/United States ; R01 NS083542/NS/NINDS NIH HHS/United States ; }, abstract = {Chronically undernourished children become stunted during their first 2 years and thereafter bear burdens of ill health for the rest of their lives. Contributors to stunting include poor nutrition and exposure to pathogens, and parental history may also play a role. However, the epigenetic impact of a poor environment on young children is largely unknown. Here we show the unfolding pattern of histone H3 lysine 4 trimethylation (H3K4me3) in children and mothers living in an urban slum in Dhaka, Bangladesh. A pattern of chromatin modification in blood cells of stunted children emerges over time and involves a global decrease in methylation at canonical locations near gene start sites and increased methylation at ectopic sites throughout the genome. This redistribution occurs at metabolic and immune genes and was specific for H3K4me3, as it was not observed for histone H3 lysine 27 acetylation in the same samples. Methylation changes in stunting globally resemble changes that occur in vitro in response to altered methylation capacity, suggesting that reduced levels of one-carbon nutrients in the diet play a key role in stunting in this population. A network of differentially expressed genes in stunted children reveals effects on chromatin modification machinery, including turnover of H3K4me3, as well as posttranscriptional gene regulation affecting immune response pathways and lipid metabolism. Consistent with these changes, reduced expression of the endocytic receptor gene LDL receptor 1 (LRP1) is a driver of stunting in a mouse model, suggesting a target for intervention.}, } @article {pmid30420517, year = {2018}, author = {Lu, CL and Pai, JA and Nogueira, L and Mendoza, P and Gruell, H and Oliveira, TY and Barton, J and Lorenzi, JCC and Cohen, YZ and Cohn, LB and Klein, F and Caskey, M and Nussenzweig, MC and Jankovic, M}, title = {Relationship between intact HIV-1 proviruses in circulating CD4+ T cells and rebound viruses emerging during treatment interruption.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11341-E11348}, pmid = {30420517}, issn = {1091-6490}, support = {UM1 AI126620/AI/NIAID NIH HHS/United States ; UM1 AI100663/AI/NIAID NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; R01 AI129795/AI/NIAID NIH HHS/United States ; P30 AI124414/AI/NIAID NIH HHS/United States ; }, abstract = {Combination antiretroviral therapy controls but does not cure HIV-1 infection because a small fraction of cells harbor latent viruses that can produce rebound viremia when therapy is interrupted. The circulating latent virus reservoir has been documented by a variety of methods, most prominently by viral outgrowth assays (VOAs) in which CD4+ T cells are activated to produce virus in vitro, or more recently by amplifying proviral near full-length (NFL) sequences from DNA. Analysis of samples obtained in clinical studies in which individuals underwent analytical treatment interruption (ATI), showed little if any overlap between circulating latent viruses obtained from outgrowth cultures and rebound viruses from plasma. To determine whether intact proviruses amplified from DNA are more closely related to rebound viruses than those obtained from VOAs, we assayed 12 individuals who underwent ATI after infusion of a combination of two monoclonal anti-HIV-1 antibodies. A total of 435 intact proviruses obtained by NFL sequencing were compared with 650 latent viruses from VOAs and 246 plasma rebound viruses. Although, intact NFL and outgrowth culture sequences showed similar levels of stability and diversity with 39% overlap, the size of the reservoir estimated from NFL sequencing was larger than and did not correlate with VOAs. Finally, intact proviruses documented by NFL sequencing showed no sequence overlap with rebound viruses; however, they appear to contribute to recombinant viruses found in plasma during rebound.}, } @article {pmid30420516, year = {2018}, author = {Chen, Z and Diaz, G and Pollicino, T and Zhao, H and Engle, RE and Schuck, P and Shen, CH and Zamboni, F and Long, Z and Kabat, J and De Battista, D and Bock, KW and Moore, IN and Wollenberg, K and Soto, C and Govindarajan, S and Kwong, PD and Kleiner, DE and Purcell, RH and Farci, P}, title = {Role of humoral immunity against hepatitis B virus core antigen in the pathogenesis of acute liver failure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11369-E11378}, pmid = {30420516}, issn = {1091-6490}, abstract = {Hepatitis B virus (HBV)-associated acute liver failure (ALF) is a dramatic clinical syndrome leading to death or liver transplantation in 80% of cases. Due to the extremely rapid clinical course, the difficulties in obtaining liver specimens, and the lack of an animal model, the pathogenesis of ALF remains largely unknown. Here, we performed a comprehensive genetic and functional characterization of the virus and the host in liver tissue from HBV-associated ALF and compared the results with those of classic acute hepatitis B in chimpanzees. In contrast with acute hepatitis B, HBV strains detected in ALF livers displayed highly mutated HBV core antigen (HBcAg), associated with increased HBcAg expression ex vivo, which was independent of viral replication levels. Combined gene and miRNA expression profiling revealed a dominant B cell disease signature, with extensive intrahepatic production of IgM and IgG in germline configuration exclusively targeting HBcAg with subnanomolar affinities, and complement deposition. Thus, HBV ALF appears to be an anomalous T cell-independent, HBV core-driven B cell disease, which results from the rare and unfortunate encounter between a host with an unusual B cell response and an infecting virus with a highly mutated core antigen.}, } @article {pmid30420515, year = {2018}, author = {Katafuchi, T and Holland, WL and Kollipara, RK and Kittler, R and Mangelsdorf, DJ and Kliewer, SA}, title = {PPARγ-K107 SUMOylation regulates insulin sensitivity but not adiposity in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12102-12111}, pmid = {30420515}, issn = {1091-6490}, support = {P01 AG051459/AG/NIA NIH HHS/United States ; R01 DK067158/DK/NIDDK NIH HHS/United States ; R01 DK108833/DK/NIDDK NIH HHS/United States ; R01 DK112826/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {The nuclear receptor peroxisome proliferator-activated receptor γ (PPARγ) is a master regulator of adipocyte differentiation and is the target for the insulin-sensitizing thiazolidinedione (TZD) drugs used to treat type 2 diabetes. In cell-based in vitro studies, the transcriptional activity of PPARγ is inhibited by covalent attachment of small ubiquitin-related modifier (SUMOylation) at K107 in its N terminus. However, whether this posttranslational modification is relevant in vivo remains unclear. Here, using mice homozygous for a mutation (K107R) that prevents SUMOylation at this position, we demonstrate that PPARγ is SUMOylated at K107 in white adipose tissue. We further show that in the context of diet-induced obesity PPARγ-K107R-mutant mice have enhanced insulin sensitivity without the corresponding increase in adiposity that typically accompanies PPARγ activation by TZDs. Accordingly, the PPARγ-K107R mutation was weaker than TZD treatment in stimulating adipocyte differentiation in vitro. Moreover, we found that both the basal and TZD-dependent transcriptomes of inguinal and epididymal white adipose tissue depots were markedly altered in the K107R-mutant mice. We conclude that PPARγ SUMOylation at K107 is physiologically relevant and may serve as a pharmacologic target for uncoupling PPARγ's beneficial insulin-sensitizing effect from its adverse effect of weight gain.}, } @article {pmid30420514, year = {2018}, author = {Orlando, L}, title = {Late Bronze Age cultural origins of dairy pastoralism in Mongolia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12083-12085}, pmid = {30420514}, issn = {1091-6490}, mesh = {Mongolia ; *Population Dynamics ; }, } @article {pmid30420513, year = {2018}, author = {Nelsen, MP and Ree, RH and Moreau, CS}, title = {Ant-plant interactions evolved through increasing interdependence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12253-12258}, pmid = {30420513}, issn = {1091-6490}, abstract = {Ant-plant interactions are diverse and abundant and include classic models in the study of mutualism and other biotic interactions. By estimating a time-scaled phylogeny of more than 1,700 ant species and a time-scaled phylogeny of more than 10,000 plant genera, we infer when and how interactions between ants and plants evolved and assess their macroevolutionary consequences. We estimate that ant-plant interactions originated in the Mesozoic, when predatory, ground-inhabiting ants first began foraging arboreally. This served as an evolutionary precursor to the use of plant-derived food sources, a dietary transition that likely preceded the evolution of extrafloral nectaries and elaiosomes. Transitions to a strict, plant-derived diet occurred in the Cenozoic, and optimal models of shifts between strict predation and herbivory include omnivory as an intermediate step. Arboreal nesting largely evolved from arboreally foraging lineages relying on a partially or entirely plant-based diet, and was initiated in the Mesozoic, preceding the evolution of domatia. Previous work has suggested enhanced diversification in plants with specialized ant-associated traits, but it appears that for ants, living and feeding on plants does not affect ant diversification. Together, the evidence suggests that ants and plants increasingly relied on one another and incrementally evolved more intricate associations with different macroevolutionary consequences as angiosperms increased their ecological dominance.}, } @article {pmid30420512, year = {2018}, author = {Ravindran, S}, title = {QnAs with Steven A. Kliewer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12081-12082}, pmid = {30420512}, issn = {1091-6490}, } @article {pmid30420511, year = {2018}, author = {Cáliz, J and Triadó-Margarit, X and Camarero, L and Casamayor, EO}, title = {A long-term survey unveils strong seasonal patterns in the airborne microbiome coupled to general and regional atmospheric circulations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12229-12234}, pmid = {30420511}, issn = {1091-6490}, abstract = {Airborne microbes (bacteria, archaea, protists, and fungi) were surveyed over a 7-y period via high-throughput massive sequencing of 16S and 18S rRNA genes in rain and snow samples collected fortnightly at a high-elevation mountain Long-Term Ecological Research (LTER) Network site (LTER-Aigüestortes, Central Pyrenees, Spain). This survey constitutes the most comprehensive mountain-top aerobiology study reported to date. The air mass origins were tracked through modeled back-trajectories and analysis of rain water chemical composition. Consistent microbial seasonal patterns were observed with highly divergent summer and winter communities recurrent in time. Indicative microbial taxa were unveiled as a forensic signature, and ubiquitous taxa were observed as common atmosphere inhabitants, highlighting aerosols as a potentially successful mechanism for global microbial dispersal. Source-tracking analyses identified freshwater, cropland, and urban biomes as the most important sources for airborne bacteria in summer, while marine and forest biomes prevailed in winter, in agreement with air mass retrotrajectories and the prevailing general and regional atmospheric circulation.}, } @article {pmid30420510, year = {2018}, author = {Hein, AM and Gil, MA and Twomey, CR and Couzin, ID and Levin, SA}, title = {Conserved behavioral circuits govern high-speed decision-making in wild fish shoals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12224-12228}, pmid = {30420510}, issn = {1091-6490}, abstract = {To evade their predators, animals must quickly detect potential threats, gauge risk, and mount a response. Putative neural circuits responsible for these tasks have been isolated in laboratory studies. However, it is unclear whether and how these circuits combine to generate the flexible, dynamic sequences of evasion behavior exhibited by wild, freely moving animals. Here, we report that evasion behavior of wild fish on a coral reef is generated through a sequence of well-defined decision rules that convert visual sensory input into behavioral actions. Using an automated system to present visual threat stimuli to fish in situ, we show that individuals initiate escape maneuvers in response to the perceived size and expansion rate of an oncoming threat using a decision rule that matches dynamics of known loom-sensitive neural circuits. After initiating an evasion maneuver, fish adjust their trajectories using a control rule based on visual feedback to steer away from the threat and toward shelter. These decision rules accurately describe evasion behavior of fish from phylogenetically distant families, illustrating the conserved nature of escape decision-making. Our results reveal how the flexible behavioral responses required for survival can emerge from relatively simple, conserved decision-making mechanisms.}, } @article {pmid30420509, year = {2018}, author = {}, title = {Correction for Sormaz et al., Default mode network can support the level of detail in experience during active task states.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11198}, doi = {10.1073/pnas.1817966115}, pmid = {30420509}, issn = {1091-6490}, } @article {pmid30420508, year = {2018}, author = {}, title = {Correction to Supporting Information for Kim et al., Yin-and-yang bifurcation of opioidergic circuits for descending analgesia at the midbrain of the mouse.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11199}, doi = {10.1073/pnas.1818273115}, pmid = {30420508}, issn = {1091-6490}, } @article {pmid30420507, year = {2018}, author = {Sakai, Y and Kawamura, S and Kawata, M}, title = {Genetic and plastic variation in opsin gene expression, light sensitivity, and female response to visual signals in the guppy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12247-12252}, pmid = {30420507}, issn = {1091-6490}, abstract = {According to the sensory drive model, variation in visual properties can lead to diverse female preferences, which in turn results in a range of male nuptial colors by way of sexual selection. However, the cause of variation in visual properties and the mechanism by which variation drives female response to visual signals remain unclear. Here, we demonstrate that both differences in the long-wavelength-sensitive 1 (LWS-1) opsin genotype and the light environment during rearing lead to variation in opsin gene expression. Opsin expression variation affects the visual sensitivity threshold to long wavelengths of light. Moreover, a behavioral assay using digitally modified video images showed that the expression of multiple opsin genes is positively correlated with the female responsiveness to images of males with luminous orange spots. The findings suggest that genetic polymorphisms and light environment in habitats induce variations in opsin gene expression levels. The variations may facilitate variations in visual sensitivity and female responsiveness to male body colors within and among populations.}, } @article {pmid30420506, year = {2018}, author = {Button, B and Goodell, HP and Atieh, E and Chen, YC and Williams, R and Shenoy, S and Lackey, E and Shenkute, NT and Cai, LH and Dennis, RG and Boucher, RC and Rubinstein, M}, title = {Roles of mucus adhesion and cohesion in cough clearance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12501-12506}, doi = {10.1073/pnas.1811787115}, pmid = {30420506}, issn = {1091-6490}, support = {P30 DK065988/DK/NIDDK NIH HHS/United States ; R01 HL125280/HL/NHLBI NIH HHS/United States ; R01 HL136961/HL/NHLBI NIH HHS/United States ; P01 HL108808/HL/NHLBI NIH HHS/United States ; }, abstract = {Clearance of intrapulmonary mucus by the high-velocity airflow generated by cough is the major rescue clearance mechanism in subjects with mucoobstructive diseases and failed cilial-dependent mucus clearance, e.g., subjects with cystic fibrosis (CF) or chronic obstructive pulmonary disease (COPD). Previous studies have investigated the mechanical forces generated at airway surfaces by cough but have not considered the effects of mucus biophysical properties on cough efficacy. Theoretically, mucus can be cleared by cough from the lung by an adhesive failure, i.e., breaking mucus-cell surface adhesive bonds and/or by cohesive failure, i.e., directly fracturing mucus. Utilizing peel-testing technologies, mucus-epithelial surface adhesive and mucus cohesive strengths were measured. Because both mucus concentration and pH have been reported to alter mucus biophysical properties in disease, the effects of mucus concentration and pH on adhesion and cohesion were compared. Both adhesive and cohesive strengths depended on mucus concentration, but neither on physiologically relevant changes in pH nor bicarbonate concentration. Mucus from bronchial epithelial cultures and patient sputum samples exhibited similar adhesive and cohesive properties. Notably, the magnitudes of both adhesive and cohesive strength exhibited similar velocity and concentration dependencies, suggesting that viscous dissipation of energy within mucus during cough determines the efficiency of cough clearance of diseased, hyperconcentrated, mucus. Calculations of airflow-induced shear forces on airway mucus related to mucus concentration predicted substantially reduced cough clearance in small versus large airways. Studies designed to improve cough clearance in subjects with mucoobstructive diseases identified reductions of mucus concentration and viscous dissipation as key therapeutic strategies.}, } @article {pmid30420505, year = {2018}, author = {Stewart-Jones, GBE and Chuang, GY and Xu, K and Zhou, T and Acharya, P and Tsybovsky, Y and Ou, L and Zhang, B and Fernandez-Rodriguez, B and Gilardi, V and Silacci-Fregni, C and Beltramello, M and Baxa, U and Druz, A and Kong, WP and Thomas, PV and Yang, Y and Foulds, KE and Todd, JP and Wei, H and Salazar, AM and Scorpio, DG and Carragher, B and Potter, CS and Corti, D and Mascola, JR and Lanzavecchia, A and Kwong, PD}, title = {Structure-based design of a quadrivalent fusion glycoprotein vaccine for human parainfluenza virus types 1-4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12265-12270}, pmid = {30420505}, issn = {1091-6490}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; P41 GM103310/GM/NIGMS NIH HHS/United States ; }, abstract = {Parainfluenza virus types 1-4 (PIV1-4) are highly infectious human pathogens, of which PIV3 is most commonly responsible for severe respiratory illness in newborns, elderly, and immunocompromised individuals. To obtain a vaccine effective against all four PIV types, we engineered mutations in each of the four PIV fusion (F) glycoproteins to stabilize their metastable prefusion states, as such stabilization had previously enabled the elicitation of high-titer neutralizing antibodies against the related respiratory syncytial virus. A cryoelectron microscopy structure of an engineered PIV3 F prefusion-stabilized trimer, bound to the prefusion-specific antibody PIA174, revealed atomic-level details for how introduced mutations improved stability as well as how a single PIA174 antibody recognized the trimeric apex of prefusion PIV3 F. Nine combinations of six newly identified disulfides and two cavity-filling mutations stabilized the prefusion PIV3 F immunogens and induced 200- to 500-fold higher neutralizing titers in mice than were elicited by PIV3 F in the postfusion conformation. For PIV1, PIV2, and PIV4, we also obtained stabilized prefusion Fs, for which prefusion versus postfusion titers were 2- to 20-fold higher. Elicited murine responses were PIV type-specific, with little cross-neutralization of other PIVs. In nonhuman primates (NHPs), quadrivalent immunization with prefusion-stabilized Fs from PIV1-4 consistently induced potent neutralizing responses against all four PIVs. For PIV3, the average elicited NHP titer from the quadrivalent immunization was more than fivefold higher than any titer observed in a cohort of over 100 human adults, highlighting the ability of a prefusion-stabilized immunogen to elicit especially potent neutralization.}, } @article {pmid30420504, year = {2018}, author = {Geary, DC}, title = {Autism in the broader context of cognitive sex differences.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12089-12091}, pmid = {30420504}, issn = {1091-6490}, mesh = {*Autistic Disorder ; Brain ; Cognition ; Female ; Humans ; Male ; *Sex Characteristics ; }, } @article {pmid30420503, year = {2018}, author = {Greenberg, DM and Warrier, V and Allison, C and Baron-Cohen, S}, title = {Testing the Empathizing-Systemizing theory of sex differences and the Extreme Male Brain theory of autism in half a million people.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12152-12157}, pmid = {30420503}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; //Medical Research Council/United Kingdom ; }, abstract = {The Empathizing-Systemizing (E-S) theory of typical sex differences suggests that individuals may be classified based on empathy and systemizing. An extension of the E-S theory, the Extreme Male Brain (EMB) theory suggests that autistic people on average have a shift towards a more masculinized brain along the E-S dimensions. Both theories have been investigated in small sample sizes, limiting their generalizability. Here we leverage two large datasets (discovery n = 671,606, including 36,648 autistic individuals primarily; and validation n = 14,354, including 226 autistic individuals) to investigate 10 predictions of the E-S and the EMB theories. In the discovery dataset, typical females on average showed higher scores on short forms of the Empathy Quotient (EQ) and Sensory Perception Quotient (SPQ), and typical males on average showed higher scores on short forms of the Autism Spectrum Quotient (AQ) and Systemizing Quotient (SQ). Typical sex differences in these measures were attenuated in autistic individuals. Analysis of "brain types" revealed that typical females on average were more likely to be Type E (EQ > SQ) or Extreme Type E and that typical males on average were more likely to be Type S (SQ > EQ) or Extreme Type S. In both datasets, autistic individuals, regardless of their reported sex, on average were "masculinized." Finally, we demonstrate that D-scores (difference between EQ and SQ) account for 19 times more of the variance in autistic traits (43%) than do other demographic variables including sex. Our results provide robust evidence in support of both the E-S and EMB theories.}, } @article {pmid30420502, year = {2018}, author = {Krois, AS and Dyson, HJ and Wright, PE}, title = {Long-range regulation of p53 DNA binding by its intrinsically disordered N-terminal transactivation domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11302-E11310}, pmid = {30420502}, issn = {1091-6490}, support = {R01 CA096865/CA/NCI NIH HHS/United States ; R01 GM075995/GM/NIGMS NIH HHS/United States ; }, abstract = {Atomic resolution characterization of the full-length p53 tetramer has been hampered by its size and the presence of extensive intrinsically disordered regions at both the N and C termini. As a consequence, the structural characteristics and dynamics of the disordered regions are poorly understood within the context of the intact p53 tetramer. Here we apply trans-intein splicing to generate segmentally 15N-labeled full-length p53 constructs in which only the resonances of the N-terminal transactivation domain (NTAD) are visible in NMR spectra, allowing us to observe this region of p53 with unprecedented detail within the tetramer. The N-terminal region is dynamically disordered in the full-length p53 tetramer, fluctuating between states in which it is free and fully exposed to solvent and states in which it makes transient contacts with the DNA-binding domain (DBD). Chemical-shift changes and paramagnetic spin-labeling experiments reveal that the amphipathic AD1 and AD2 motifs of the NTAD interact with the DNA-binding surface of the DBD through primarily electrostatic interactions. Importantly, this interaction inhibits binding of nonspecific DNA to the DBD while having no effect on binding to a specific p53 recognition element. We conclude that the NTAD:DBD interaction functions to enhance selectivity toward target genes by inhibiting binding to nonspecific sites in genomic DNA. This work provides some of the highest-resolution data on the disordered N terminus of the nearly 180-kDa full-length p53 tetramer and demonstrates a regulatory mechanism by which the N terminus of p53 transiently interacts with the DBD to enhance target site discrimination.}, } @article {pmid30420501, year = {2018}, author = {Kernbach, JM and Yeo, BTT and Smallwood, J and Margulies, DS and Thiebaut de Schotten, M and Walter, H and Sabuncu, MR and Holmes, AJ and Gramfort, A and Varoquaux, G and Thirion, B and Bzdok, D}, title = {Subspecialization within default mode nodes characterized in 10,000 UK Biobank participants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12295-12300}, pmid = {30420501}, issn = {1091-6490}, abstract = {The human default mode network (DMN) is implicated in several unique mental capacities. In this study, we tested whether brain-wide interregional communication in the DMN can be derived from population variability in intrinsic activity fluctuations, gray-matter morphology, and fiber tract anatomy. In a sample of 10,000 UK Biobank participants, pattern-learning algorithms revealed functional coupling states in the DMN that are linked to connectivity profiles between other macroscopical brain networks. In addition, DMN gray matter volume was covaried with white matter microstructure of the fornix. Collectively, functional and structural patterns unmasked a possible division of labor within major DMN nodes: Subregions most critical for cortical network interplay were adjacent to subregions most predictive of fornix fibers from the hippocampus that processes memories and places.}, } @article {pmid30420500, year = {2018}, author = {Legrand, M and McConnell, JR and Preunkert, S and Arienzo, M and Chellman, N and Gleason, K and Sherwen, T and Evans, MJ and Carpenter, LJ}, title = {Alpine ice evidence of a three-fold increase in atmospheric iodine deposition since 1950 in Europe due to increasing oceanic emissions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12136-12141}, pmid = {30420500}, issn = {1091-6490}, abstract = {Iodine is an important nutrient and a significant sink of tropospheric ozone, a climate-forcing gas and air pollutant. Ozone interacts with seawater iodide, leading to volatile inorganic iodine release that likely represents the largest source of atmospheric iodine. Increasing ozone concentrations since the preindustrial period imply that iodine chemistry and its associated ozone destruction is now substantially more active. However, the lack of historical observations of ozone and iodine means that such estimates rely primarily on model calculations. Here we use seasonally resolved records from an Alpine ice core to investigate 20th century changes in atmospheric iodine. After carefully considering possible postdepositional changes in the ice core record, we conclude that iodine deposition over the Alps increased by at least a factor of 3 from 1950 to the 1990s in the summer months, with smaller increases during the winter months. We reproduce these general trends using a chemical transport model and show that they are due to increased oceanic iodine emissions, coupled to a change in iodine speciation over Europe from enhanced nitrogen oxide emissions. The model underestimates the increase in iodine deposition by a factor of 2, however, which may be due to an underestimate in the 20th century ozone increase. Our results suggest that iodine's impact on the Northern Hemisphere atmosphere accelerated over the 20th century and show a coupling between anthropogenic pollution and the availability of iodine as an essential nutrient to the terrestrial biosphere.}, } @article {pmid30420499, year = {2018}, author = {Shen, Z and Neil, TR and Robert, D and Drinkwater, BW and Holderied, MW}, title = {Biomechanics of a moth scale at ultrasonic frequencies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12200-12205}, pmid = {30420499}, issn = {1091-6490}, support = {BB/N009991/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The wings of moths and butterflies are densely covered in scales that exhibit intricate shapes and sculptured nanostructures. While certain butterfly scales create nanoscale photonic effects, moth scales show different nanostructures suggesting different functionality. Here we investigate moth-scale vibrodynamics to understand their role in creating acoustic camouflage against bat echolocation, where scales on wings provide ultrasound absorber functionality. For this, individual scales can be considered as building blocks with adapted biomechanical properties at ultrasonic frequencies. The 3D nanostructure of a full Bunaea alcinoe moth forewing scale was characterized using confocal microscopy. Structurally, this scale is double layered and endowed with different perforation rates on the upper and lower laminae, which are interconnected by trabeculae pillars. From these observations a parameterized model of the scale's nanostructure was formed and its effective elastic stiffness matrix extracted. Macroscale numerical modeling of scale vibrodynamics showed close qualitative and quantitative agreement with scanning laser Doppler vibrometry measurement of this scale's oscillations, suggesting that the governing biomechanics have been captured accurately. Importantly, this scale of B. alcinoe exhibits its first three resonances in the typical echolocation frequency range of bats, suggesting it has evolved as a resonant absorber. Damping coefficients of the moth-scale resonator and ultrasonic absorption of a scaled wing were estimated using numerical modeling. The calculated absorption coefficient of 0.50 agrees with the published maximum acoustic effect of wing scaling. Understanding scale vibroacoustic behavior helps create macroscopic structures with the capacity for broadband acoustic camouflage.}, } @article {pmid30420498, year = {2018}, author = {Demas, AR and Sharma, AI and Wong, W and Early, AM and Redmond, S and Bopp, S and Neafsey, DE and Volkman, SK and Hartl, DL and Wirth, DF}, title = {Mutations in Plasmodium falciparum actin-binding protein coronin confer reduced artemisinin susceptibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12799-12804}, doi = {10.1073/pnas.1812317115}, pmid = {30420498}, issn = {1091-6490}, support = {R01 AI099105/AI/NIAID NIH HHS/United States ; }, mesh = {4-Butyrolactone/*analogs & derivatives/genetics ; Antimalarials/pharmacology ; Artemisinins/*pharmacology ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Drug Resistance/genetics ; Gene Editing/methods ; Humans ; Malaria, Falciparum/drug therapy/parasitology ; Microfilament Proteins/*genetics ; Mutation/*genetics ; Plasmodium falciparum/*drug effects/*genetics ; WD40 Repeats/genetics ; }, abstract = {Drug resistance is an obstacle to global malaria control, as evidenced by the recent emergence and rapid spread of delayed artemisinin (ART) clearance by mutant forms of the PfKelch13 protein in Southeast Asia. Identifying genetic determinants of ART resistance in African-derived parasites is important for surveillance and for understanding the mechanism of resistance. In this study, we carried out long-term in vitro selection of two recently isolated West African parasites (from Pikine and Thiès, Senegal) with increasing concentrations of dihydroartemisinin (DHA), the biologically active form of ART, over a 4-y period. We isolated two parasite clones, one from each original isolate, that exhibited enhanced survival to DHA in the ring-stage survival assay. Whole-genome sequence analysis identified 10 mutations in seven different genes. We chose to focus on the gene encoding PfCoronin, a member of the WD40-propeller domain protein family, because mutations in this gene occurred in both independent selections, and the protein shares the β-propeller motif with PfKelch13 protein. For functional validation, when pfcoronin mutations were introduced into the parental parasites by CRISPR/Cas9-mediated gene editing, these mutations were sufficient to reduce ART susceptibility in the parental lines. The discovery of a second gene for ART resistance may yield insights into the molecular mechanisms of resistance. It also suggests that pfcoronin mutants could emerge as a nonkelch13 type of resistance to ART in natural settings.}, } @article {pmid30420497, year = {2018}, author = {Woods, R and Turvey, ST and Brace, S and MacPhee, RDE and Barnes, I}, title = {Ancient DNA of the extinct Jamaican monkey Xenothrix reveals extreme insular change within a morphologically conservative radiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {12769-12774}, doi = {10.1073/pnas.1808603115}, pmid = {30420497}, issn = {1091-6490}, mesh = {Adaptation, Physiological/genetics ; Animals ; Biodiversity ; Caribbean Region ; Cell Nucleus/genetics ; DNA, Ancient/*analysis ; Fossils ; Genome, Mitochondrial/genetics ; Haplorhini/*genetics ; Phylogeny ; Water ; }, abstract = {The insular Caribbean until recently contained a diverse mammal fauna including four endemic platyrrhine primate species, all of which died out during the Holocene. Previous morphological studies have attempted to establish how these primates are related to fossil and extant platyrrhines, whether they represent ancient or recent colonists, and whether they constitute a monophyletic group. These efforts have generated multiple conflicting hypotheses, from close sister-taxon relationships with several different extant platyrrhines to derivation from a stem platyrrhine lineage outside the extant Neotropical radiation. This diversity of opinion reflects the fact that Caribbean primates were morphologically extremely unusual, displaying numerous autapomorphies and apparently derived conditions present across different platyrrhine clades. Here we report ancient DNA data for an extinct Caribbean primate: a limited-coverage entire mitochondrial genome and seven regions of nuclear genome for the most morphologically derived taxon, the Jamaican monkey Xenothrix mcgregori We demonstrate that Xenothrix is part of the existing platyrrhine radiation rather than a late-surviving stem platyrrhine, despite its unusual adaptations, and falls within the species-rich but morphologically conservative titi monkey clade (Callicebinae) as sister to the newly recognized genus Cheracebus These results are not congruent with previous morphology-based hypotheses and suggest that even morphologically conservative lineages can exhibit phenetic plasticity in novel environments like those found on islands. Xenothrix and Cheracebus diverged ca. 11 Ma, but primates have been present in the Caribbean since 17.5-18.5 Ma, indicating that Caribbean primate diversity was generated by multiple over-water colonizations.}, } @article {pmid30420496, year = {2018}, author = {Boswell, RG and Sun, W and Suzuki, S and Kober, H}, title = {Training in cognitive strategies reduces eating and improves food choice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11238-E11247}, pmid = {30420496}, issn = {1091-6490}, support = {K12 DA000167/DA/NIDA NIH HHS/United States ; P50 DA009241/DA/NIDA NIH HHS/United States ; }, abstract = {Obesity rates continue to rise alarmingly, with dire health implications. One contributing factor is that individuals frequently forgo healthy foods in favor of inexpensive, high-calorie, unhealthy foods. One important mechanism underlying these choices is food craving: Craving increases with exposure to unhealthy foods (and food cues, such as advertisements) and prospectively predicts eating and weight. Prior work has shown that cognitive regulation strategies that emphasize the negative consequences of unhealthy foods reduce craving. In Studies 1 and 2, we show that cognitive strategies also increase craving for healthy foods by emphasizing their positive benefits, and change food valuation (willingness to pay) for both healthy and unhealthy foods. In Studies 3 and 4, we demonstrate that brief training in cognitive strategies ("Regulation of Craving Training"; ROC-T) increases subsequent healthy (vs. unhealthy) food choices. This was striking because this change in food choices generalized to nontrained items. Importantly, in Study 5, we show that brief training in cognitive strategies also reduces food consumption by 93-121 calories. Consumed calories correlated with changes in food choice. Finally, in Study 6, we show that the training component of ROC-T is necessary, above and beyond any effect of framing. Across all studies (NTOTAL = 1,528), we find that cognitive strategies substantially change craving and food valuation, and that training in cognitive strategies improves food choices by 5.4-11.2% and reduces unhealthy eating, including in obese individuals. Thus, these findings have important theoretical, public health, and clinical implications for obesity prevention and treatment.}, } @article {pmid30420495, year = {2018}, author = {Farrell, JM and Brown, SP}, title = {Evolution of bacterial trade in a two-species community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11874-11875}, pmid = {30420495}, issn = {1091-6490}, mesh = {Bacteria ; *Biological Evolution ; *Symbiosis ; }, } @article {pmid30420275, year = {2018}, author = {Dagg, JL}, title = {Motives and merits of counterfactual histories of science.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.shpsc.2018.11.001}, pmid = {30420275}, issn = {1879-2499}, abstract = {I consider the motives of historians devising counterfactual histories, analyze the narrative structure of these histories, and assess their merits. Richard Evans attacked counterfactual histories as motivated by wishful thinking. And he claimed that they could not contribute anything to the understanding of the past because they are concerned "with pointing out supposedly preferable alternatives." Both claims can be refuted with two particular counterfactual histories of biology. An analysis of the narrative structure of counterfactual histories suggests objective criteria that can distinguish those that have been designed, in order to reach a certain narrative ending, from those that were open-ended at the beginning. These criteria are then applied to two examples from the history of biology: Bowler's Darwin Deleted and Radick's 'Other Histories, Other Biologies.' Radick did not determine his counterfactual in advance, to meet a certain narrative ending. This refutes the first claim (wishful thinking). Bowler self-avowedly did design his counterfactual in advance, but its narrative ending still contributes to understanding. In particular, it shows that the idea of natural selection is not necessarily associated with its social discontents. This refutes the second claim (cannot contribute to understanding).}, } @article {pmid30419969, year = {2018}, author = {Wijesundara, M and Wijerathna, C and Wijerathna, K and Wijerathna, R and Wijethunga, S and Wijewardana, A and Wickramasinghe, A and Rathish, D}, title = {A significant association between examination results and self-satisfaction with English language proficiency: preliminary findings among pre-clinical undergraduates.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {807}, pmid = {30419969}, issn = {1756-0500}, abstract = {OBJECTIVES: Learning methods and other related factors influence the success of medical undergraduates. This study aims at finding factors associated with the end of pre-clinical stream examination results among medical undergraduates of the Rajarata University of Sri Lanka. The results of this study will inform the tutors to plan and implement teaching methods as well as to guide the social welfare of the undergraduates. In general, we believe this study has the potential to improve the medical undergraduate's academic performance.

RESULTS: Eighty-six per cent (112/130) of medical undergraduates have passed the examination and rest was referred. Logistic regression revealed a significant association between examination results and self-satisfaction for English language proficiency (P = 0.048). Passing the examination was more likely with high self-satisfaction for English language proficiency [odds ratio = 6.063 (95% CI 1.014 to 36.249)]. Also, a significant association between obtaining a class at the examination and using peer-revision notes (P = 0.019) was revealed. Obtaining a class at the examination was less likely with the frequent use of peer-revision notes [odds ratio = 0.228 (95% CI 0.066 to 0.790)].}, } @article {pmid30419962, year = {2018}, author = {Faghri, J and Nouri, S and Jalalifar, S and Zalipoor, M and Halaji, M}, title = {Investigation of antimicrobial susceptibility, class I and II integrons among Pseudomonas aeruginosa isolates from hospitalized patients in Isfahan, Iran.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {806}, pmid = {30419962}, issn = {1756-0500}, abstract = {OBJECTIVES: The role of integrons in the transfer of antibiotic resistance is one of the important issues, therefore, this study is aimed to investigate antibiotic resistance pattern and prevalence of class 1 and 2 integrons in P. aeruginosa isolated.

RESULTS: Out of 72 confirmed P. aeruginosa isolates, 50% were from ICU patients. Antibacterial susceptibility pattern showed that isolates were most resistant to ceftazidime (76.4%) and colistin was the most effective antibiotic (100%) and molecular analysis of class I and II integrons showed 55.5% and 29.1% of isolates were positive, respectively and the proportions of MDR isolates were significantly higher among integron-positive isolates with 73.6% compared to negative isolates with 22.9%. Our results showed that there was a correlation among class 1 and 2 integrons with MDR P. aeruginosa isolates. According to the importance of integrons in acquisition and dissemination of antibiotics resistance genes, the performance of antibiotic surveillance programs and investigating the role of integrons is recommended to control the spreading of antibiotics resistance genes.}, } @article {pmid30419949, year = {2018}, author = {Silverman, JD and Durand, HK and Bloom, RJ and Mukherjee, S and David, LA}, title = {Dynamic linear models guide design and analysis of microbiota studies within artificial human guts.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {202}, pmid = {30419949}, issn = {2049-2618}, support = {IIS-1320357//National Science Foundation (US)/ ; DMS1613261//National Science Foundation (US)/ ; DMS-1418261//National Science Foundation/ ; IIS-1546331//National Science Foundation/ ; 1R01DK116187//National Institutes of Health/ ; None//University of North Carolina Center for Gastrointestinal Biology and Disease/ ; NNX16AO69A//Translational Research Institute/ ; None//Hartwell Foundation/ ; DMS-1045153//National Science Foundation (US)/ ; }, abstract = {BACKGROUND: Artificial gut models provide unique opportunities to study human-associated microbiota. Outstanding questions for these models' fundamental biology include the timescales on which microbiota vary and the factors that drive such change. Answering these questions though requires overcoming analytical obstacles like estimating the effects of technical variation on observed microbiota dynamics, as well as the lack of appropriate benchmark datasets.

RESULTS: To address these obstacles, we created a modeling framework based on multinomial logistic-normal dynamic linear models (MALLARDs) and performed dense longitudinal sampling of four replicate artificial human guts over the course of 1 month. The resulting analyses revealed how the ratio of biological variation to technical variation from sample processing depends on sampling frequency. In particular, we find that at hourly sampling frequencies, 76% of observed variation could be ascribed to technical sources, which could also skew the observed covariation between taxa. We also found that the artificial guts demonstrated replicable trajectories even after a recovery from a transient feed disruption. Additionally, we observed irregular sub-daily oscillatory dynamics associated with the bacterial family Enterobacteriaceae within all four replicate vessels.

CONCLUSIONS: Our analyses suggest that, beyond variation due to sequence counting, technical variation from sample processing can obscure temporal variation from biological sources in artificial gut studies. Our analyses also supported hypotheses that human gut microbiota fluctuates on sub-daily timescales in the absence of a host and that microbiota can follow replicable trajectories in the presence of environmental driving forces. Finally, multiple aspects of our approach are generalizable and could ultimately be used to facilitate the design and analysis of longitudinal microbiota studies in vivo.}, } @article {pmid30419937, year = {2018}, author = {Derakhshani, H and Plaizier, JC and De Buck, J and Barkema, HW and Khafipour, E}, title = {Association of bovine major histocompatibility complex (BoLA) gene polymorphism with colostrum and milk microbiota of dairy cows during the first week of lactation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {203}, pmid = {30419937}, issn = {2049-2618}, abstract = {BACKGROUND: The interplay between host genotype and commensal microbiota at different body sites can have important implications for health and disease. In dairy cows, polymorphism of bovine major histocompatibility complex (BoLA) gene has been associated with susceptibility to several infectious diseases, most importantly mastitis. However, mechanisms underlying this association are yet poorly understood. In the present study, we sought to explore the association of BoLA gene polymorphism with the dynamics of mammary microbiota during the first week of lactation.

RESULTS: Colostrum and milk samples were collected from multiparous Holstein dairy cows at the day of calving and days 1 and 6 after calving. Microbiota profiling was performed using high-throughput sequencing of the V1-V2 regions of the bacterial 16S rRNA genes and ITS2 region of the fungal ribosomal DNA. Polymorphism of BoLA genes was determined using PCR-RFLP of exon 2 of the BoLA-DRB3. In general, transition from colostrum to milk resulted in increased species richness and diversity of both bacterial and fungal communities. The most dominant members of intramammary microbiota included Staphylococcus, Ruminococcaceae, and Clostridiales within the bacterial community and Alternaria, Aspergillus, Candida, and Cryptococcus within the fungal community. Comparing the composition of intramammary microbiota between identified BoLA-DRB3.2 variants (n = 2) revealed distinct clustering pattern on day 0, whereas this effect was not significant on the microbiota of milk samples collected on subsequent days. On day 0, proportions of several non-aureus Staphylococcus (NAS) OTUs, including those aligned to Staphylococcus equorum, Staphylococcus gallinarum, Staphylococcus sciuri, and Staphylococcus haemolyticus, were enriched within the microbiota of one of the BoLA-DRB3.2 variants, whereas lactic acid bacteria (LAB) including Lactobacillus and Enterococcus were enriched within the colostrum microbiota of the other variant.

CONCLUSION: Our results suggest a potential role for BoLA-gene polymorphism in modulating the composition of colostrum microbiota in dairy cows. Determining whether BoLA-mediated shifts in the composition of colostrum microbiota are regulated directly by immune system or indirectly by microbiota-derived colonization resistant can have important implications for future development of preventive/therapeutic strategies for controlling mastitis.}, } @article {pmid30419897, year = {2018}, author = {Martínez, JA and Rodriguez, A and Moreno, F and Flores, N and Lara, AR and Ramírez, OT and Gosset, G and Bolivar, F}, title = {Metabolic modeling and response surface analysis of an Escherichia coli strain engineered for shikimic acid production.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {102}, pmid = {30419897}, issn = {1752-0509}, support = {240519//Consejo Nacional de Ciencia y Tecnología/ ; IN209618//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, abstract = {BACKGROUND: Classic metabolic engineering strategies often induce significant flux imbalances to microbial metabolism, causing undesirable outcomes such as suboptimal conversion of substrates to products. Several mathematical frameworks have been developed to understand the physiological and metabolic state of production strains and to identify genetic modification targets for improved bioproduct formation. In this work, a modeling approach was applied to describe the physiological behavior and the metabolic fluxes of a shikimic acid overproducing Escherichia coli strain lacking the major glucose transport system, grown on complex media.

RESULTS: The obtained flux distributions indicate the presence of high fluxes through the pentose phosphate and Entner-Doudoroff pathways, which could limit the availability of erythrose-4-phosphate for shikimic acid production even with high flux redirection through the pentose phosphate pathway. In addition, highly active glyoxylate shunt fluxes and a pyruvate/acetate cycle are indicators of overflow glycolytic metabolism in the tested conditions. The analysis of the combined physiological and flux response surfaces, enabled zone allocation for different physiological outputs within variant substrate conditions. This information was then used for an improved fed-batch process designed to preserve the metabolic conditions that were found to enhance shikimic acid productivity. This resulted in a 40% increase in the shikimic acid titer (60 g/L) and 70% increase in volumetric productivity (2.45 gSA/L*h), while preserving yields, compared to the batch process.

CONCLUSIONS: The combination of dynamic metabolic modeling and experimental parameter response surfaces was a successful approach to understand and predict the behavior of a shikimic acid producing strain under variable substrate concentrations. Response surfaces were useful for allocating different physiological behavior zones with different preferential product outcomes. Both model sets provided information that could be applied to enhance shikimic acid production on an engineered shikimic acid overproducing Escherichia coli strain.}, } @article {pmid30419831, year = {2018}, author = {Bazzo, BR and de Carvalho, LM and Carazzolle, MF and Pereira, GAG and Colombo, CA}, title = {Development of novel EST-SSR markers in the macaúba palm (Acrocomia aculeata) using transcriptome sequencing and cross-species transferability in Arecaceae species.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {276}, pmid = {30419831}, issn = {1471-2229}, support = {2014/07265-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Arecaceae/*genetics ; Chromosome Mapping ; Expressed Sequence Tags ; Genetic Markers/genetics ; *Genetic Variation ; Genome, Plant/*genetics ; High-Throughput Nucleotide Sequencing ; Microsatellite Repeats/genetics ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: The macaúba palm is a novel feedstock for oil production suitable for multiple uses, including as biodiesel and in the food and cosmetic industries. As an efficient alternative, the macaúba palm has limited genomic resources, particularly expressed sequence tag (EST) markers. We report a comprehensive set of validated EST-simple sequence repeat (SSR) markers by using transcriptome sequencing, its application in genetic diversity analysis and cross transferability in other palm trees with environmental and economic importance.

RESULTS: In this study, a total of 418 EST-SSRs were identified to be unique for one transcript and region; 232 EST-SSRs were selected, with trinucleotide repeats being the most frequent motif, representing 380 (90.9%), followed by composited (4.5%), di- (3.6%), and hexanucleotides (3.6%). A total of 145 EST-SSRs (62.5%) were validated for consistent amplification in seventeen macaúba palm samples, and 100 were determined to be polymorphic with PIC values ranging from 0.25 to 0.77. Genetic diversity analysis was performed with the 20 most informative EST-SSR markers showing a distinct separation of the different groups of macaúba palm. Additionally, these 145 markers were transferred in six other palm species resulting in transferability rates of 99% (144) in Acrocomia intumescens, 98% (143) in Acrocomia totai, 80.7% (117 EST-EST) in African oil palm (Elaeis guineensis) and peach palm (Bactris gasipaes) samples, 70% (102) in the juçara palm (Euterpe edulis) and 71.7% (104) in the hat palm (Sabal causiarum). Analysis of genetic distance showed a high separation in accordance with geographic location, establishing distinct groups by genera.

CONCLUSIONS: The EST markers identified in our study are a valuable resource and provide a genomic tool for genetic mapping and further genetic studies, as well as evaluation of co-location between QTLs and functionally associated markers.}, } @article {pmid30419829, year = {2018}, author = {Davey, MP and Palmer, BG and Armitage, E and Vergeer, P and Kunin, WE and Woodward, FI and Quick, WP}, title = {Natural variation in tolerance to sub-zero temperatures among populations of Arabidopsis lyrata ssp. petraea.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {277}, pmid = {30419829}, issn = {1471-2229}, support = {NE/C507837/1//Natural Environment Research Council/ ; RPG-2017-077//Leverhulme Trust/ ; }, mesh = {*Acclimatization ; Arabidopsis/*physiology ; Chlorophyll/metabolism ; Fluorescence ; Freezing ; Photosynthesis/physiology ; Photosystem II Protein Complex/metabolism ; Plant Leaves/physiology ; }, abstract = {BACKGROUND: Temperature is one of the most important abiotic factors limiting plant growth and productivity. Many plants exhibit cold acclimation to prepare for the likelihood of freezing as temperatures decrease towards 0 °C. The physiological mechanisms associated with enabling increased tolerance to sub-zero temperatures vary between species and genotypes. Geographically and climatically diverse populations of Arabidopsis lyrata ssp. petraea were examined for their ability to survive, maintain functional photosynthetic parameters and cellular electrolyte leakage integrity after being exposed to sub-zero temperatures. The duration of cold acclimation prior to sub-zero temperatures was also manipulated (2 and 14 days).

RESULTS: We found that there was significant natural variation in tolerances to sub-zero temperatures among populations of A. petraea. The origin of the population affected the acclimation response and survival after exposure to sub-zero temperatures. Cold acclimation of plants prior to sub-zero temperatures affected the maximum quantum efficiency of photosystem II (PSII) (Fv/Fm) in that plants that were cold acclimated for longer periods had higher values of Fv/Fm as a result of sub-zero temperatures. The inner immature leaves were better able to recover Fv/Fm from sub-zero temperatures than mature outer leaves. The Irish population (Leitrim) acclimated faster, in terms of survival and electrolyte leakage than the Norwegian population (Helin).

CONCLUSION: The ability to survive, recover photosynthetic processes and cellular electrolyte leakage after exposure to sub-zero temperatures is highly dependent on the duration of cold acclimation.}, } @article {pmid30419826, year = {2018}, author = {Han, TT and Liu, WC and Lu, YT}, title = {General control non-repressible 20 (GCN20) functions in root growth by modulating DNA damage repair in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {274}, pmid = {30419826}, issn = {1471-2229}, support = {#31470378//National Natural Science Foundation of China/ ; }, mesh = {ATP-Binding Cassette Transporters/genetics/*metabolism ; Arabidopsis/cytology/*genetics/growth & development/radiation effects ; Arabidopsis Proteins/genetics/*metabolism ; Cell Cycle ; DNA Damage ; *DNA Repair ; DNA, Plant/genetics ; Genes, Reporter ; Meristem/cytology/genetics/growth & development/radiation effects ; Plant Roots/cytology/genetics/growth & development/radiation effects ; Plants, Genetically Modified ; Ultraviolet Rays ; }, abstract = {BACKGROUND: Most ABC transporters are engaged in transport of various compounds, but its subfamily F lacks transmembrane domain essential for chemical transportation. Thus the function of subfamily F remains further elusive.

RESULTS: Here, we identified General Control Non-Repressible 20 (GCN20), a member of subfamily F, as new factor for DNA damage repair in root growth. While gcn20-1 mutant had a short primary root with reduced meristem size and cell number, similar primary root lengths were assayed in both wild-type and GCN20::GCN20 gcn20-1 plants, indicating the involvement of GCN20 in root elongation. Further experiments with EdU incorporation and comet assay demonstrated that gcn20-1 displays increased cell cycle arrest at G2/M checkpoint and accumulates more damaged DNA. This is possible due to impaired ability of DNA repair in gcn20-1 since gcn20-1 seedlings are hypersensitive to DNA damage inducers MMC and MMS compared with the wild type plants. This note was further supported by the observation that gcn20-1 is more sensitive than the wild type when subjected to UV treatment in term of changes of both fresh weight and survival rate.

CONCLUSIONS: Our study indicates that GCN20 functions in primary root growth by modulating DNA damage repair in Arabidopsis. Our study will be useful to understand the functions of non-transporter ABC proteins in plant growth.}, } @article {pmid30419824, year = {2018}, author = {Sweet, ME and Cocciolo, A and Slavov, D and Jones, KL and Sweet, JR and Graw, SL and Reece, TB and Ambardekar, AV and Bristow, MR and Mestroni, L and Taylor, MRG}, title = {Transcriptome analysis of human heart failure reveals dysregulated cell adhesion in dilated cardiomyopathy and activated immune pathways in ischemic heart failure.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {812}, pmid = {30419824}, issn = {1471-2164}, support = {UL1 TR001082//National Institutes of Health/ ; R01 HL109209/HL/NHLBI NIH HHS/United States ; R01 HL069071/HL/NHLBI NIH HHS/United States ; R01 HL69071//National Institutes of Health/ ; 14-CVD 03//Fondation Leducq/ ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01 116906//National Institutes of Health/ ; R01 HL109209//National Institutes of Health/ ; }, abstract = {BACKGROUND: Current heart failure (HF) treatment is based on targeting symptoms and left ventricle dysfunction severity, relying on a common HF pathway paradigm to justify common treatments for HF patients. This common strategy may belie an incomplete understanding of heterogeneous underlying mechanisms and could be a barrier to more precise treatments. We hypothesized we could use RNA-sequencing (RNA-seq) in human heart tissue to delineate HF etiology-specific gene expression signatures.

RESULTS: RNA-seq from 64 human left ventricular samples: 37 dilated (DCM), 13 ischemic (ICM), and 14 non-failing (NF). Using a multi-analytic approach including covariate adjustment for age and sex, differentially expressed genes (DEGs) were identified characterizing HF and disease-specific expression. Pathway analysis investigated enrichment for biologically relevant pathways and functions. DCM vs NF and ICM vs NF had shared HF-DEGs that were enriched for the fetal gene program and mitochondrial dysfunction. DCM-specific DEGs were enriched for cell-cell and cell-matrix adhesion pathways. ICM-specific DEGs were enriched for cytoskeletal and immune pathway activation. Using the ICM and DCM DEG signatures from our data we were able to correctly classify the phenotypes of 24/31 ICM and 32/36 DCM samples from publicly available replication datasets.

CONCLUSIONS: Our results demonstrate the commonality of mitochondrial dysfunction in end-stage HF but more importantly reveal key etiology-specific signatures. Dysfunctional cell-cell and cell-matrix adhesion signatures typified DCM whereas signals related to immune and fibrotic responses were seen in ICM. These findings suggest that transcriptome signatures may distinguish end-stage heart failure, shedding light on underlying biological differences between ICM and DCM.}, } @article {pmid30419822, year = {2018}, author = {Kurepa, J and Shull, TE and Karunadasa, SS and Smalle, JA}, title = {Modulation of auxin and cytokinin responses by early steps of the phenylpropanoid pathway.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {278}, pmid = {30419822}, issn = {1471-2229}, support = {HATCH project 1009329//USDA National Institute of Food and Agriculture/ ; 1//Kentucky Tobacco Research and Development Center/ ; IOS-0919991//Division of Integrative Organismal Systems/ ; }, mesh = {Arabidopsis/genetics/growth & development/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Biosynthetic Pathways ; Cinnamates/metabolism ; Cytokinins/*metabolism ; F-Box Proteins/genetics/metabolism ; Genes, Reporter ; Indoleacetic Acids/*metabolism ; Kelch Repeat ; Phenylalanine Ammonia-Lyase/genetics/metabolism ; Phenylpropionates/*metabolism ; Plant Growth Regulators/*metabolism ; Plants, Genetically Modified ; Seedlings/genetics/growth & development/physiology ; *Signal Transduction ; Trans-Cinnamate 4-Monooxygenase/genetics/metabolism ; }, abstract = {BACKGROUND: The phenylpropanoid pathway is responsible for the synthesis of numerous compounds important for plant growth and responses to the environment. In the first committed step of phenylpropanoid biosynthesis, the enzyme phenylalanine ammonia-lyase (PAL) deaminates L-phenylalanine into trans-cinnamic acid that is then converted into p-coumaric acid by cinnamate-4-hydroxylase (C4H). Recent studies showed that the Kelch repeat F-box (KFB) protein family of ubiquitin ligases control phenylpropanoid biosynthesis by promoting the proteolysis of PAL. However, this ubiquitin ligase family, alternatively named Kiss Me Deadly (KMD), was also implicated in cytokinin signaling as it was shown to promote the degradation of type-B ARRs, including the key response activator ARR1. Considering that ubiquitin ligases typically have narrow target specificity, this dual targeting of structurally and functionally unrelated proteins appeared unusual.

RESULTS: Here we show that the KFBs indeed target PAL but not ARR1. Moreover, we show that changes in early phenylpropanoid biosynthesis alter cytokinin sensitivity - as reported earlier - but that the previously documented cytokinin growth response changes are primarily the result of altered auxin signaling. We found that reduced PAL accumulation decreased, whereas the loss of C4H function increased the strength of the auxin response. The combined loss of function of both enzymes led to a decrease in auxin sensitivity, indicating that metabolic events upstream of C4H control auxin sensitivity. This auxin/phenylpropanoid interaction impacts both shoot and root development and revealed an auxin-dependent stimulatory effect of trans-cinnamic acid feeding on leaf expansion and thus biomass accumulation.

CONCLUSIONS: Collectively, our results show that auxin-regulated plant growth is fine-tuned by early steps in phenylpropanoid biosynthesis and suggest that metabolites accumulating upstream of the C4H step impact the auxin response mechanism.}, } @article {pmid30419821, year = {2018}, author = {Szołtysek, K and Janus, P and Zając, G and Stokowy, T and Walaszczyk, A and Widłak, W and Wojtaś, B and Gielniewski, B and Cockell, S and Perkins, ND and Kimmel, M and Widlak, P}, title = {RRAD, IL4I1, CDKN1A, and SERPINE1 genes are potentially co-regulated by NF-κB and p53 transcription factors in cells exposed to high doses of ionizing radiation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {813}, pmid = {30419821}, issn = {1471-2164}, support = {2013/08/M/NZ1/00935//Narodowe Centrum Nauki (PL)/ ; 2014/13/B/NZ3/04650//Narodowe Centrum Nauki (PL)/ ; }, abstract = {BACKGROUND: The cellular response to ionizing radiation involves activation of p53-dependent pathways and activation of the atypical NF-κB pathway. The crosstalk between these two transcriptional networks include (co)regulation of common gene targets. Here we looked for novel genes potentially (co)regulated by p53 and NF-κB using integrative genomics screening in human osteosarcoma U2-OS cells irradiated with a high dose (4 and 10 Gy). Radiation-induced expression in cells with silenced TP53 or RELA (coding the p65 NF-κB subunit) genes was analyzed by RNA-Seq while radiation-enhanced binding of p53 and RelA in putative regulatory regions was analyzed by ChIP-Seq, then selected candidates were validated by qPCR.

RESULTS: We identified a subset of radiation-modulated genes whose expression was affected by silencing of both TP53 and RELA, and a subset of radiation-upregulated genes where radiation stimulated binding of both p53 and RelA. For three genes, namely IL4I1, SERPINE1, and CDKN1A, an antagonistic effect of the TP53 and RELA silencing was consistent with radiation-enhanced binding of both p53 and RelA. This suggested the possibility of a direct antagonistic (co)regulation by both factors: activation by NF-κB and inhibition by p53 of IL4I1, and activation by p53 and inhibition by NF-κB of CDKN1A and SERPINE1. On the other hand, radiation-enhanced binding of both p53 and RelA was observed in a putative regulatory region of the RRAD gene whose expression was downregulated both by TP53 and RELA silencing, which suggested a possibility of direct (co)activation by both factors.

CONCLUSIONS: Four new candidates for genes directly co-regulated by NF-κB and p53 were revealed.}, } @article {pmid30419820, year = {2018}, author = {Ebersbach, P and Stehle, F and Kayser, O and Freier, E}, title = {Chemical fingerprinting of single glandular trichomes of Cannabis sativa by Coherent anti-Stokes Raman scattering (CARS) microscopy.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {275}, pmid = {30419820}, issn = {1471-2229}, support = {031A360E//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Alkenes/chemistry/metabolism ; Cannabinoids/*chemistry/metabolism ; Cannabis/*chemistry ; Dronabinol/chemistry/metabolism ; Imaging, Three-Dimensional ; Microscopy, Electron, Scanning ; Monoterpenes/chemistry/metabolism ; Oils, Volatile/*metabolism ; Plants, Medicinal ; Secondary Metabolism ; Spectrum Analysis, Raman/*methods ; Terpenes/chemistry/metabolism ; Trichomes/*chemistry ; }, abstract = {BACKGROUND: Cannabis possesses a rich spectrum of phytochemicals i.e. cannabinoids, terpenes and phenolic compounds of industrial and medicinal interests. Most of these high-value plant products are synthesised in the disk cells and stored in the secretory cavity in glandular trichomes. Conventional trichome analysis was so far based on optical microscopy, electron microscopy or extraction based methods that are either limited to spatial or chemical information. Here we combine both information to obtain the spatial distribution of distinct secondary metabolites on a single-trichome level by applying Coherent anti-Stokes Raman scattering (CARS), a microspectroscopic technique, to trichomes derived from sepals of a drug- and a fibre-type.

RESULTS: Hyperspectral CARS imaging in combination with a nonlinear unmixing method allows to identify and localise Δ9-tetrahydrocannabinolic acid (THCA) in the secretory cavity of drug-type trichomes and cannabidiolic acid (CBDA)/myrcene in the secretory cavity of fibre-type trichomes, thus enabling an easy discrimination between high-THCA and high-CBDA producers. A unique spectral fingerprint is found in the disk cells of drug-type trichomes, which is most similar to cannabigerolic acid (CBGA) and is not found in fibre-type trichomes. Furthermore, we differentiate between different cell types by a combination of CARS with simultaneously acquired two-photon fluorescence (TPF) of chlorophyll a from chloroplasts and organic fluorescence mainly arising from cell walls enabling 3D visualisation of the essential oil distribution and cellular structures.

CONCLUSION: Here we demonstrate a label-free and non-destructive method to analyse the distribution of secondary metabolites and distinguish between different cell and chemo-types with high spatial resolution on a single trichome. The record of chemical fingerprints of single trichomes offers the possibility to optimise growth conditions as well as guarantee a direct process control for industrially cultivated medicinal Cannabis plants. Moreover, this method is not limited to Cannabis related issues but can be widely implemented for optimising and monitoring all kinds of natural or biotechnological production processes with simultaneous spatial and chemical information.}, } @article {pmid30419818, year = {2018}, author = {Jing, C and Liu, C and Liu, F and Gao, Y and Liu, Y and Guan, Z and Xuan, B and Yu, Y and Yang, G}, title = {Novel human monoclonal antibodies targeting the F subunit of leukocidins reduce disease progression and mortality caused by Staphylococcus aureus.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {181}, pmid = {30419818}, issn = {1471-2180}, support = {31370170//National Natural Science Foundation of China/ ; 7142119//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {BACKGROUND: Staphylococcus aureus is a leading cause of Gram-positive bacterial infections worldwide; however, the treatment of S. aureus infection has become increasingly difficult due to the prevalence of methicillin-resistant S. aureus strains, highlighting the urgent need for the development of novel strategies. The complexity of S. aureus pathogenesis relies on virulence factors. Recent studies have demonstrated that leukocidins expressed by the majority of clinical isolates play important roles in the pathogenesis of S. aureus.

RESULTS: In this study, we developed three human monoclonal antibodies against all F-components of leukocidins HlgABC, LukSF, and LukED with high affinity. These antibodies were found to be capable of blocking leukocidin-mediated cell lysis in vitro. Furthermore, the antibodies dramatically reduced disease progression and mortality after S. aureus infection in vivo.

CONCLUSIONS: Our findings revealed that neutralizing bicomponent leukocidins may be a promising strategy to combat infections caused by S. aureus.}, } @article {pmid30419816, year = {2018}, author = {Li, J and Liu, J and Campanile, G and Plastow, G and Zhang, C and Wang, Z and Cassandro, M and Gasparrini, B and Salzano, A and Hua, G and Liang, A and Yang, L}, title = {Novel insights into the genetic basis of buffalo reproductive performance.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {814}, pmid = {30419816}, issn = {1471-2164}, support = {CARS-37-04B//Modern Agro- industry Technology Research System/ ; 31772602 and 31772604//International Cooperation and Exchange Programme/ ; }, abstract = {BACKGROUND: Fertility is a complex trait that has a major impact on the development of the buffalo industry. Genome-wide association study (GWAS) has increased the ability to detect genes influencing complex traits, and many important genes related to reproductive traits have been identified in ruminants. However, reproductive traits are influenced by many factors. The development of the follicle is one of the most important internal processes affecting fertility. Genes found by GWAS to be associated with follicular development may directly affect fertility. The present study combined GWAS and RNA-seq of follicular granulosa cells to identify important genes which may affect fertility in the buffalo.

RESULTS: The 90 K Affymetrix Axiom Buffalo SNP Array was used to identify the SNPs, genomic regions, and genes that were associated with reproductive traits. A total of 40 suggestive loci (related to 28 genes) were identified to be associated with six reproductive traits (first, second and third calving age, calving interval, the number of services per conception and open days). Interestingly, the mRNA expressions of 25 of these genes were also observed in buffalo follicular granulosa cells. The IGFBP7 gene showed high level of expression during whole antral follicle growth. The knockdown of IGFBP7 in buffalo granulosa cells promoted cell apoptosis and hindered cell proliferation, and increased the production of progesterone and estradiol. Furthermore, a notable signal was detected at 2.3-2.7 Mb on the equivalent of bovine chromosome 5 associated with age at second calving, calving interval, and open days.

CONCLUSIONS: The genes associated with buffalo reproductive traits in this study may have effect on fertility by regulating of follicular growth. These results may have important implications for improving buffalo breeding programs through application of genomic information.}, } @article {pmid30419815, year = {2018}, author = {Cheung, CT and Pasquier, J and Bouleau, A and Nguyen, T and Chesnel, F and Guiguen, Y and Bobe, J}, title = {Double maternal-effect: duplicated nucleoplasmin 2 genes, npm2a and npm2b, with essential but distinct functions are shared by fish and tetrapods.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {167}, pmid = {30419815}, issn = {1471-2148}, mesh = {Animals ; Conserved Sequence/genetics ; Evolution, Molecular ; Female ; Fishes/*genetics ; Gene Duplication ; Gene Expression Profiling ; *Genes, Duplicate ; Genome ; Humans ; Nucleoplasmins/*genetics/metabolism ; Peptides/chemistry ; Phylogeny ; Protein Domains ; Synteny/genetics ; Zebrafish/embryology/genetics ; Zebrafish Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: Nucleoplasmin 2 (npm2) is an essential maternal-effect gene that mediates early embryonic events through its function as a histone chaperone that remodels chromatin. Recently, two npm2 (npm2a and npm2b) genes have been annotated in zebrafish. Thus, we examined the evolution of npm2a and npm2b in a variety of vertebrates, their potential phylogenetic relationships, and their biological functions using knockout models via the CRISPR/cas9 system.

RESULTS: We demonstrated that the two npm2 duplicates exist in a wide range of vertebrates, including sharks, ray-finned fish, amphibians, and sauropsids, while npm2a was lost in coelacanth and mammals, as well as some specific teleost lineages. Using phylogeny and synteny analyses, we traced their origins to the early stages of vertebrate evolution. Our findings suggested that npm2a and npm2b resulted from an ancient local gene duplication, and their functions diverged although key protein domains were conserved. We then investigated their functions by examining their tissue distribution in a wide variety of species and found that they shared ovarian-specific expression, a key feature of maternal-effect genes. We also demonstrated that both npm2a and npm2b are maternally-inherited transcripts in vertebrates, and that they play essential, but distinct, roles in early embryogenesis using zebrafish knockout models. Both npm2a and npm2b function early during oogenesis and may play a role in cortical granule function that impact egg activation and fertilization, while npm2b is also involved in early embryogenesis.

CONCLUSION: These novel findings will broaden our knowledge on the evolutionary history of maternal-effect genes and underlying mechanisms that contribute to vertebrate reproductive success. In addition, our results demonstrate the existence of a newly described maternal-effect gene, npm2a, that contributes to egg competence, an area that still requires further comprehension.}, } @article {pmid30419812, year = {2018}, author = {Pan, Y and An, H and Fu, T and Zhao, S and Zhang, C and Xiao, G and Zhang, J and Zhao, X and Hu, G}, title = {Characterization of Streptococcus pluranimalium from a cattle with mastitis by whole genome sequencing and functional validation.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {182}, pmid = {30419812}, issn = {1471-2180}, support = {132102110126//Science and Technology Key Project Foundation of Henan Province/ ; U1504326//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Streptococcus pluranimalium is a new member of the Streptococcus genus isolated from multiple different animal hosts. It has been identified as a pathogen associated with subclinical mastitis, valvular endocarditis and septicaemia in animals. Moreover, this bacterium has emerged as a new pathogen for human infective endocarditis and brain abscess. However, the patho-biological properties of S. pluranimalium remain virtually unknown. The aim of this study was to determine the complete genome sequence of S. pluranimalium strain TH11417 isolated from a cattle with mastitis, and to characterize its antimicrobial resistance, virulence, and carbon catabolism.

RESULTS: The genome of S. pluranimalium TH11417, determined by single-molecule real-time (SMRT) sequencing, consists of 2,065,522 base pair (bp) with a G + C content of 38.65%, 2,007 predicted coding sequence (CDS), 58 transfer RNA (tRNA) genes and five ribosome RNA (rRNA) operons. It contains a novel ISSpl1 element (a memeber of the IS3 family) and a Ф11417.1 prophage that carries the mef(A), msr(D) and lnu(C) genes. Consistently, our antimicrobial susceptibility test confirmed that S. pluranimalium TH11417 was resistant to erythromycin and lincomycin. However, this strain did not show virulence in murine pneumonia (intranasal inoculation, 107 colony forming unit - CFU) and sepsis (intraperitoneal inoculation, 107 CFU) models. Additionally, this strain is able to grow with glucose, lactose or galactose as the sole carbon source, and possesses a lactose-specific phosphoenolpyruvate-dependent phosphotransferase system (PTS).

CONCLUSIONS: We reported the first whole genome sequence of S. pluranimalium isolated from a cattle with mastitis. It harbors a prophage carrying the mef(A), msr(D) and lnu(C) genes, and is avirulent in the murine infection model.}, } @article {pmid30419811, year = {2018}, author = {Bhoite, R and Onyemaobi, I and Si, P and Siddique, KHM and Yan, G}, title = {Identification and validation of QTL and their associated genes for pre-emergent metribuzin tolerance in hexaploid wheat (Triticum aestivum L.).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {102}, pmid = {30419811}, issn = {1471-2156}, abstract = {BACKGROUND: Herbicide tolerance is an important trait that allows effective weed management in wheat crops. Genetic knowledge of metribuzin tolerance in wheat is needed to develop new cultivars for the industry. Here, we evaluated metribuzin tolerance in a recombinant inbred line (RIL) mapping population derived from Synthetic W7984 and Opata 85 over two consecutive years to identify quantitative trait loci (QTL) contributing to the trait. Herbicide tolerance was measured by two chlorophyll traits, SPAD chlorophyll content index (CCI) and visual senescence score (SNS). The markers associated with major QTL from Synthetic W7984, positively contributing to reduced phytotoxic effects under herbicide treatment were validated in two F3/4 recombinant inbred populations developed from crosses of Synthetic W7984 × Westonia and Synthetic W7984 × Lang.

RESULTS: Composite interval mapping (CIM) identified four QTL, two on chromosome 4A and one each on chromosomes 2D and 1A. The chromosomal position of the two QTL mapped on 4A within 10 cM intervals was refined and validated by multiple interval mapping (MIM). The major QTL affecting both measures of tolerance jointly explained 42 and 45% of the phenotypic variation by percentage CCI reduction and SNS, respectively. The identified QTL have a pure additive effect. The metribuzin tolerant allele of markers, Xgwm33 and Xbarc343, conferred lower phytotoxicity and explained the maximum phenotypic variation of 28.8 and 24.5%, respectively. The approximate physical localization of the QTL revealed the presence of five candidate genes (ribulose-bisphosphate carboxylase, oxidoreductase (rbcS), glycosyltransferase, serine/threonine-specific protein kinase and phosphotransferase) with a direct role in photosynthesis and/or metabolic detoxification pathways.

CONCLUSION: Metribuzin causes photo-inhibition by interrupting electron flow in PSII. Consequently, chlorophyll traits enabled the measure of high proportion of genetic variability in the mapping population. The validated molecular markers associated with metribuzin tolerance mediating QTL may be used in marker-assisted breeding to select metribuzin tolerant lines. Alternatively, validated favourable alleles could be introgressed into elite wheat cultivars to enhance metribuzin tolerance and improve grain yield in dryland farming for sustainable wheat production.}, } @article {pmid30419810, year = {2018}, author = {Lowe, EK and Garm, AL and Ullrich-Lüter, E and Cuomo, C and Arnone, MI}, title = {The crowns have eyes: multiple opsins found in the eyes of the crown-of-thorns starfish Acanthaster planci.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {168}, pmid = {30419810}, issn = {1471-2148}, mesh = {Amino Acid Motifs ; Animals ; Base Sequence ; Bayes Theorem ; Biological Evolution ; Cilia/metabolism ; Eye/*metabolism ; Gene Expression Regulation ; Opsins/genetics/*metabolism ; Phylogeny ; Starfish/genetics/*metabolism ; }, abstract = {BACKGROUND: Opsins are G protein-coupled receptors used for both visual and non-visual photoreception, and these proteins evolutionarily date back to the base of the bilaterians. In the current sequencing age, phylogenomic analysis has proven to be a powerful tool, facilitating the increase in knowledge about diversity within the opsin subclasses and, so far, at least nine types of opsins have been identified. Within echinoderms, opsins have been studied in Echinoidea and Ophiuroidea, which do not possess proper image forming eyes, but rather widely dispersed dermal photoreceptors. However, most species of Asteroidea, the starfish, possess true eyes and studying them will shed light on the diversity of opsin usage within echinoderms and help resolve the evolutionary history of opsins.

RESULTS: Using high-throughput RNA sequencing, we have sequenced and analyzed the transcriptomes of different Acanthaster planci tissue samples: eyes, radial nerve, tube feet and a mixture of tissues from other organs. At least ten opsins were identified, and eight of them were found significantly differentially expressed in both eyes and radial nerve, with R-opsin being the most highly expressed in the eye.

CONCLUSION: This study provides new important insight into the involvement of opsins in visual and nonvisual photoreception. Of relevance, we found the first indication of an r-opsin photopigment expressed in a well-developed visual eye in a deuterostome animal. Additionally, we provided tissue specific A. planci transcriptomes that will aid in future Evo Devo studies.}, } @article {pmid30419809, year = {2018}, author = {Hu, J and Gao, Y and He, J and Zheng, Y and Shang, X}, title = {WebNetCoffee: a web-based application to identify functionally conserved proteins from Multiple PPI networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {422}, pmid = {30419809}, issn = {1471-2105}, support = {61772426//National Natural Science Foundation of China/ ; 61702420//National Natural Science Foundation of China/ ; 61332014//National Natural Science Foundation of China/ ; 2017M613203//Postdoctoral Research Foundation of China/ ; }, mesh = {Computational Biology/*methods ; Humans ; Protein Interaction Mapping/*methods ; }, abstract = {BACKGROUND: The discovery of functionally conserved proteins is a tough and important task in system biology. Global network alignment provides a systematic framework to search for these proteins from multiple protein-protein interaction (PPI) networks. Although there exist many web servers for network alignment, no one allows to perform global multiple network alignment tasks on users' test datasets.

RESULTS: Here, we developed a web server WebNetcoffee based on the algorithm of NetCoffee to search for a global network alignment from multiple networks. To build a series of online test datasets, we manually collected 218,339 proteins, 4,009,541 interactions and many other associated protein annotations from several public databases. All these datasets and alignment results are available for download, which can support users to perform algorithm comparison and downstream analyses.

CONCLUSION: WebNetCoffee provides a versatile, interactive and user-friendly interface for easily running alignment tasks on both online datasets and users' test datasets, managing submitted jobs and visualizing the alignment results through a web browser. Additionally, our web server also facilitates graphical visualization of induced subnetworks for a given protein and its neighborhood. To the best of our knowledge, it is the first web server that facilitates the performing of global alignment for multiple PPI networks.

AVAILABILITY: http://www.nwpu-bioinformatics.com/WebNetCoffee.}, } @article {pmid30419808, year = {2018}, author = {Miraee-Nedjad, S and Sims, PFG and Schwartz, JM and Doig, AJ}, title = {Effect of IAPP on the proteome of cultured Rin-5F cells.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {9}, pmid = {30419808}, issn = {1471-2091}, support = {BB/C008219/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Islet amyloid polypeptide (IAPP) or amylin deposits can be found in the islets of type 2 diabetes patients. The peptide is suggested to be involved in the etiology of the disease through formation of amyloid deposits and destruction of β islet cells, though the underlying molecular events leading from IAPP deposition to β cell death are still largely unknown.

RESULTS: We used OFFGEL™ proteomics to study how IAPP exposure affects the proteome of rat pancreatic insulinoma Rin-5F cells. The OFFGEL™ methodology is highly effective at generating quantitative data on hundreds of proteins affected by IAPP, with its accuracy confirmed by In Cell Western and Quantitative Real Time PCR results. Combining data on individual proteins identifies pathways and protein complexes affected by IAPP. IAPP disrupts protein synthesis and degradation, and induces oxidative stress. It causes decreases in protein transport and localization. IAPP disrupts the regulation of ubiquitin-dependent protein degradation and increases catabolic processes. IAPP causes decreases in protein transport and localization, and affects the cytoskeleton, DNA repair and oxidative stress.

CONCLUSIONS: Results are consistent with a model where IAPP aggregates overwhelm the ability of a cell to degrade proteins via the ubiquitin system. Ultimately this leads to apoptosis. IAPP aggregates may be also toxic to the cell by causing oxidative stress, leading to DNA damage or by decreasing protein transport. The reversal of any of these effects, perhaps by targeting proteins which alter in response to IAPP, may be beneficial for type II diabetes.}, } @article {pmid30419807, year = {2018}, author = {Xie, B and Liu, X and Yang, J and Cheng, J and Gu, J and Xue, S}, title = {PIAS1 protects against myocardial ischemia-reperfusion injury by stimulating PPARγ SUMOylation.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {24}, pmid = {30419807}, issn = {1471-2121}, support = {81670225//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Myocardial ischemia-reperfusion injury (IRI) has become one of the most serious complications after reperfusion therapy in patients with acute myocardial infarction. Small ubiquitin-like modification (SUMOylation) is a reversible process, including SUMO E1-, E2-, and E3-mediated SUMOylation and SUMO-specific protease-mediated deSUMOylation, with the latter having been shown to play a vital role in myocardial IRI previously. However, little is known about the function and regulation of SUMO E3 ligases in myocardial IRI.

RESULTS: In this study, we found dramatically decreased expression of PIAS1 after ischemia/reperfusion (I/R) in mouse myocardium and H9C2 cells. PIAS1 deficiency aggravated apoptosis and inflammation of cardiomyocytes via activating the NF-κB pathway after I/R. Mechanistically, we identified PIAS1 as a specific E3 ligase for PPARγ SUMOylation. Moreover, H9C2 cells treated with hypoxia/reoxygenation (H/R) displayed reduced PPARγ SUMOylation as a result of down-regulated PIAS1, and act an anti-apoptotic and anti-inflammatory function through repressing NF-κB activity. Finally, overexpression of PIAS1 in H9C2 cells could remarkably ameliorate I/R injury.

CONCLUSIONS: Collectively, our findings demonstrate the crucial role of PIAS1-mediated PPARγ SUMOylation in protecting against myocardial IRI.}, } @article {pmid30419805, year = {2018}, author = {Cai, Z and Villumsen, TM and Asp, T and Guldbrandtsen, B and Sahana, G and Lund, MS}, title = {SNP markers associated with body size and pelt length in American mink (Neovison vison).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {103}, pmid = {30419805}, issn = {1471-2156}, support = {0603-00519B//Innovation Fund Denmark/ ; }, abstract = {BACKGROUND: Identification of genes underlying production traits is a key aim of the mink research community. Recent availability of genomic tools have opened the possibility for faster genetic progress in mink breeding. Availability of mink genome assembly allows genome-wide association studies in mink.

RESULTS: In this study, we used genotyping-by-sequencing to obtain single nucleotide polymorphism (SNP) genotypes of 2496 mink. After multiple rounds of filtering, we retained 28,336 high quality SNPs and 2352 individuals for a genome-wide association study (GWAS). We performed the first GWAS for body weight, behavior, along with 10 traits related to fur quality in mink.

CONCLUSIONS: Combining association results with existing functional information of genes and mammalian phenotype databases, we proposed WWC3, MAP2K4, SLC7A1 and USP22 as candidate genes for body weight and pelt length in mink.}, } @article {pmid30418640, year = {2018}, author = {Cury, J and Oliveira, PH and de la Cruz, F and Rocha, EPC}, title = {Host Range and Genetic Plasticity Explain the Coexistence of Integrative and Extrachromosomal Mobile Genetic Elements.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2850}, doi = {10.1093/molbev/msy182}, pmid = {30418640}, issn = {1537-1719}, } @article {pmid30418639, year = {2018}, author = {Castellano, D and James, J and Eyre-Walker, A}, title = {Nearly Neutral Evolution across the Drosophila melanogaster Genome.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2685-2694}, doi = {10.1093/molbev/msy164}, pmid = {30418639}, issn = {1537-1719}, abstract = {Under the nearly neutral theory of molecular evolution, the proportion of effectively neutral mutations is expected to depend upon the effective population size (Ne). Here, we investigate whether this is the case across the genome of Drosophila melanogaster using polymorphism data from North American and African lines. We show that the ratio of the number of nonsynonymous and synonymous polymorphisms is negatively correlated to the number of synonymous polymorphisms, even when the nonindependence is accounted for. The relationship is such that the proportion of effectively neutral nonsynonymous mutations increases by ∼45% as Ne is halved. However, we also show that this relationship is steeper than expected from an independent estimate of the distribution of fitness effects from the site frequency spectrum. We investigate a number of potential explanations for this and show, using simulation, that this is consistent with a model of genetic hitchhiking: Genetic hitchhiking depresses diversity at neutral and weakly selected sites, but has little effect on the diversity of strongly selected sites.}, } @article {pmid30418109, year = {2019}, author = {Fidalgo, C and Proença, DN and Morais, PV and Henriques, I and Alves, A}, title = {The endosphere of the salt marsh plant Halimione portulacoides is a diversity hotspot for the genus Salinicola: description of five novel species Salinicola halimionae sp. nov., Salinicola aestuarinus sp. nov., Salinicola endophyticus sp. nov., Salinicola halophyticus sp. nov. and Salinicola lusitanus sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {46-62}, doi = {10.1099/ijsem.0.003061}, pmid = {30418109}, issn = {1466-5034}, abstract = {Seven endophytic strains were isolated from the halophyte Halimione portulacoides, collected from Ria de Aveiro, Portugal. To determine their exact taxonomic position, comparative analyses were performed with these strains and closely related type strains of Salinicola species. Genome sequencing and comparison indicated that five of the seven isolated strains comprised distinct and novel species (average nucleotide identity <0.95; in silico DNA-DNA hybridization <70 %; G+C difference >1 %). Multilocus sequence analysis was performed using gyrB, rpoD and 16S rRNA gene sequences from the novel and type strains to determine their phylogenetic positions. The novel strains are facultative anaerobes, mesophilic, facultative alkaliphic and halophilic, test positive for catalase and oxidase activities, for hydrolysis of Tween 20 and phosphate, for production of indole-3-acetic acid, but do not produce H2S. Ubiquinone UQ-9 is present in major amounts in all strains. The major fatty acids include C16 : 0 and the summed feature containing C18 : 1ω7c and/or C18 : 1ω6c. The DNA G+C content ranges from 60.6 to 65.8 mol%. Five strains were confirmed as new species belonging to the genus Salinicola, for which the names Salinicolahalimionae sp. nov. (type strain CPA60T=CECT 9338T=LMG 30107T), Salinicolaaestuarinus sp. nov. (type strain CPA62T=CECT 9339T=LMG 30108T), Salinicolaendophyticus sp. nov. (type strain CPA92T=CECT 9340T=LMG 30109T), Salinicolahalophyticus sp. nov. (type strain CR45T=CECT 9341T=LMG 30105T) and Salinicola lusitanus sp. nov. (type strain CR50T=CECT 9342T=LMG 30106T) are proposed.}, } @article {pmid30417945, year = {2019}, author = {Thomson, CE and Hadfield, JD}, title = {No evidence for sibling or parent-offspring coadaptation in a wild population of blue tits, despite high power.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {28-41}, doi = {10.1111/evo.13642}, pmid = {30417945}, issn = {1558-5646}, support = {//EPSRC/ ; UF150696//Royal Society/ ; UF100660//Royal Society/ ; NE/F015275/1//Natural Environment Research Council/ ; NE/P000924/1//Natural Environment Research Council/ ; }, abstract = {Parent and offspring behaviors are expected to act as both the agents and targets of selection. This may generate parent-offspring coadaptation in which parent and offspring behaviors become genetically correlated in a way that increases inclusive fitness. Cross-fostering has been used to study parent-offspring coadaptation, with the prediction that offspring raised by non-relatives, or parents raising non-relatives, should suffer fitness costs. Using long-term data from more than 400 partially crossed broods of blue tits (Cyanistes caeruleus), we show that there is no difference in mass or survival between crossed and non-crossed chicks. However, previous studies for which the evidence for parent-offspring coadaptation is strongest compare chicks from fully crossed broods with those from non-crossed broods. When parent-offspring coadaptation acts at the level of the brood then partial cross-fostering experiments are not expected to show evidence of coadaptation. To test this, we performed an additional experiment (163 broods) in which clutches were either fully crossed, non-crossed, or partially crossed. In agreement with the long-term data, there was no evidence for parent-offspring coadaptation on offspring fitness despite high power. In addition there was no evidence of effects on parental fitness, nor evidence of sibling coadaptation, although the power of these tests was more modest.}, } @article {pmid30417475, year = {2018}, author = {Grunst, AS and Grunst, ML and Gonser, RA and Tuttle, EM}, title = {Developmental stress and telomere dynamics in a genetically polymorphic species.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13400}, pmid = {30417475}, issn = {1420-9101}, support = {1R01GM084229//National Institutes of Health/ ; DUE-0934648//Division of Undergraduate Education/ ; }, abstract = {A central objective of evolutionary biology is understanding variation in life-history trajectories and the rate of aging, or senescence. Senescence can be affected by trade-offs and behavioural strategies in adults but may also be affected by developmental stress. Developmental stress can accelerate telomere degradation, with long-term longevity and fitness consequences. Little is known regarding whether variation in developmental stress and telomere dynamics contributes to patterns of senescence during adulthood. We investigated this question in the dimorphic white-throated sparrow (Zonotrichia albicollis), a species in which adults of the two morphs exhibit established differences in behavioural strategy and patterns of senescence, and also evaluated the relationship between oxidative stress and telomere length. Tan morph females, which exhibit high levels of unassisted parental care, display faster reproductive senescence than white females, and faster actuarial senescence than all of the other morph-sex classes. We hypothesized that high oxidative stress and telomere attrition in tan female nestlings could contribute to this pattern, since tan females are small and potentially at a competitive disadvantage even as nestlings. Nestlings that were smaller than nest mates had higher oxidative stress, and nestlings with high oxidative stress and fast growth rates displayed shorter telomeres. However, we found no consistent morph-sex differences in oxidative stress or telomere length. Results suggest that oxidative stress and fast growth contribute to developmental telomere attrition, with potential ramifications for adults, but that developmental oxidative stress and telomere dynamics do not account for morph-sex differences in senescence during adulthood.}, } @article {pmid30417348, year = {2018}, author = {Lasne, C and Van Heerwaarden, B and Sgrò, CM and Connallon, T}, title = {Quantifying the relative contributions of the X chromosome, autosomes, and mitochondrial genome to local adaptation.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13647}, pmid = {30417348}, issn = {1558-5646}, abstract = {During local adaptation with gene flow, some regions of the genome are inherently more responsive to selection than others. Recent theory predicts that X-linked genes should disproportionately contribute to local adaptation relative to other genomic regions, yet this prediction remains to be tested. We carried out a multigeneration crossing scheme, using two cline-end populations of Drosophila melanogaster, to estimate the relative contributions of the X chromosome, autosomes, and mitochondrial genome to divergence in four traits involved in local adaptation (wing size, resistance to heat, desiccation, and starvation stresses). We found that the mitochondrial genome and autosomes contributed significantly to clinal divergence in three of the four traits. In contrast, the X made no significant contribution to divergence in these traits. Given the small size of the mitochondrial genome, our results indicate that it plays a surprisingly large role in clinal adaptation. In contrast, the X, which represents roughly 20% of the Drosophila genome, contributes negligibly-a pattern that conflicts with theoretical predictions. These patterns reinforce recent work implying a central role of mitochondria in climatic adaptation, and suggest that different genomic regions may play fundamentally different roles in processes of divergence with gene flow.}, } @article {pmid30417345, year = {2018}, author = {Muñoz, MI}, title = {Digest: Early exposure to facial cues facilitates facial learning in paper wasps.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2830-2831}, doi = {10.1111/evo.13644}, pmid = {30417345}, issn = {1558-5646}, abstract = {Tibbetts et al. evaluated the influence of the rearing environment on the facial learning capacity of the paper wasp Polistes metricus. Wasps reared with cues signaling individual identity learned to discriminate faces more accurately than wasps reared in the absence of facial cues. These findings indicate that developmental plasticity plays a significant role in the evolution of animal communication systems.}, } @article {pmid30416000, year = {2019}, author = {Romer, KA and de Rooij, DG and Kojima, ML and Page, DC}, title = {Corrigendum to "Isolating mitotic and meiotic germ cells from male mice by developmental synchronization, staging, and sorting" [Dev. Biol. 443 (2018) 19-34].}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {113}, doi = {10.1016/j.ydbio.2018.10.021}, pmid = {30416000}, issn = {1095-564X}, } @article {pmid30415827, year = {2019}, author = {Estrela, S and Libby, E and Van Cleve, J and Débarre, F and Deforet, M and Harcombe, WR and Peña, J and Brown, SP and Hochberg, ME}, title = {Environmentally Mediated Social Dilemmas.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {6-18}, doi = {10.1016/j.tree.2018.10.004}, pmid = {30415827}, issn = {1872-8383}, abstract = {By consuming and producing environmental resources, organisms inevitably change their habitats. The consequences of such environmental modifications can be detrimental or beneficial not only to the focal organism but also to other organisms sharing the same environment. Social evolution theory has been very influential in studying how social interactions mediated by public 'goods' or 'bads' evolve by emphasizing the role of spatial structure. The environmental dimensions driving these interactions, however, are typically abstracted away. We propose here a new, environment-mediated taxonomy of social behaviors where organisms are categorized by their production or consumption of environmental factors that can help or harm others in the environment. We discuss microbial examples of our classification and highlight the importance of environmental intermediates more generally.}, } @article {pmid30415265, year = {2018}, author = {Köppl, C and Wilms, V and Russell, IJ and Nothwang, HG}, title = {Evolution of Endolymph Secretion and Endolymphatic Potential Generation in the Vertebrate Inner Ear.}, journal = {Brain, behavior and evolution}, volume = {92}, number = {1-2}, pages = {1-31}, doi = {10.1159/000494050}, pmid = {30415265}, issn = {1421-9743}, abstract = {The ear of extant vertebrates reflects multiple independent evolutionary trajectories. Examples include the middle ear or the unique specializations of the mammalian cochlea. Another striking difference between vertebrate inner ears concerns the differences in the magnitude of the endolymphatic potential. This differs both between the vestibular and auditory part of the inner ear as well as between the auditory periphery in different vertebrates. Here we provide a comparison of the cellular and molecular mechanisms in different endorgans across vertebrates. We begin with the lateral line and vestibular systems, as they likely represent plesiomorphic conditions, then review the situation in different vertebrate auditory endorgans. All three systems harbor hair cells bathed in a high (K+) environment. Superficial lateral line neuromasts are bathed in an electrogenically maintained high (K+) microenvironment provided by the complex gelatinous cupula. This is associated with a positive endocupular potential. Whether this is a special or a universal feature of lateral line and possibly vestibular cupulae remains to be discovered. The vestibular system represents a closed system with an endolymph that is characterized by an enhanced (K+) relative to the perilymph. Yet only in land vertebrates does (K+) exceed (Na+). The endolymphatic potential ranges from +1 to +11 mV, albeit we note intriguing reports of substantially higher potentials of up to +70 mV in the cupula of ampullae of the semicircular canals. Similarly, in the auditory system, a high (K+) is observed. However, in contrast to the vestibular system, the positive endolymphatic potential varies more substantially between vertebrates, ranging from near zero mV to approximately +100 mV. The tissues generating endolymph in the inner ear show considerable differences in cell types and location. So-called dark cells and the possibly homologous ionocytes in fish appear to be the common elements, but there is always at least one additional cell type present. To inspire research in this field, we propose a classification for these cell types and discuss potential evolutionary relationships. Their molecular repertoire is largely unknown and provides further fertile ground for future investigation. Finally, we propose that the ultimate selective pressure for an increased endolymphatic potential, as observed in mammals and to a lesser extent in birds, is specifically to maintain the AC component of the hair-cell receptor potential at high frequencies. In summary, we identify intriguing questions for future directions of research into the molecular and cellular basis of the endolymph in the different compartments of the inner ear. The answers will provide important insights into evolutionary and developmental processes in a sensory organ essential to many species, including humans.}, } @article {pmid30415261, year = {2018}, author = {Mann, MD and Frank, LG and Glickman, SE and Towe, AL}, title = {Brain and Body Size Relations among Spotted Hyenas (Crocuta crocuta).}, journal = {Brain, behavior and evolution}, volume = {92}, number = {1-2}, pages = {82-95}, doi = {10.1159/000494125}, pmid = {30415261}, issn = {1421-9743}, abstract = {The relationship between brain size and body size across species "from mouse to elephant" is described by a function of positive slope. Almost uniformly, the relationship between brain size and body size within a species has a positive slope, though this is less steep than across species. The spotted hyena, Crocuta crocuta, differs from most other mammals in a number of ways including the fact that, on average, adult females weigh more than adult males and occasionally display greater body lengths. Brains of 5 female and 4 male hyenas were weighed in the field near Moyale in Northern Kenya, and body weights and body lengths were obtained from the same animals. When our analyses of brain/body relationships in these animals revealed an unanticipated negative relationship between brain size and body length, we extended our measurements to include intracranial volume in 19 skulls (8 females and 11 males) from the collection at the Museum of Vertebrate Zoology, University of California Berkeley; body weights and lengths were also available. A third dataset was formed by measuring intracranial volumes in 60 spotted hyena skulls (27 females and 33 males) in the Natural History Museum, London, UK; body lengths and intracranial volumes were available. Brain/body size slopes, in general, were not significantly different from zero except in 3 cases: brain weight/body length for Moyale males alone and males and females together, and cranial volume/body weight for Museum of Vertebrate Zoology males and females together. Although most of the slopes were not significantly different from zero, they were all negative, and a statistical test which combined probabilities from the 3 datasets supports the conclusion that there is a negative relationship between brain size and body size in spotted hyenas. Possible explanations for the negative slopes are discussed, including costs and benefits of large brains and large bodies and physiological mechanisms.}, } @article {pmid30415023, year = {2018}, author = {Frajman, B and Záveská, E and Gamisch, A and Moser, T and , and Schönswetter, P}, title = {Integrating phylogenomics, phylogenetics, morphometrics, relative genome size and ecological niche modelling disentangles the diversification of Eurasian Euphorbia seguieriana s. l. (Euphorbiaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ympev.2018.10.046}, pmid = {30415023}, issn = {1095-9513}, abstract = {Next generation sequencing has revolutionised biology. Restriction-associated DNA sequencing (RADseq) has primarily been used to study infraspecific relationships but has also been applied in multi-species phylogenomic analyses. In this study, we used a combination of phylogenomic (with RADseq data) and phylogenetic (with sequences of the nuclear internal transcribed spacer, ITS) methods to explore relationships within the taxonomically intricate Euphorbia seguieriana s. l., one of the most widespread Euphorbia taxa inhabiting zonal and extrazonal steppes from Iberia to Central Asia. In the inferred phylogenies the southeastern Balkan and Anatolian populations were clearly separated, supporting the distinction of E. niciciana from E. seguieriana at the species level. Within E. seguieriana, the populations from the Caucasus, Iran, and easternmost Anatolia were sister to all other populations based on RADseq, making necessary the description of a new, morphologically divergent subspecies, E. seguieriana subsp. armeniaca. Conversely, additional studies are needed to understand the status of the E. seguieriana subsp. hohenackeri, which is sympatric with E. seguieriana subsp. armeniaca. Niche analyses indicated that differences in the climatic niche between E. niciciana and E. seguieriana are relatively small compared with the climatic differences between the regions over which they are distributed. Contrary to previous believes, E. niciciana and E. seguieriana are allopatric and have likely diverged during the Pleistocene in two different glacial refugia as suggested by distribution modelling. Euphorbia niciciana nowadays has a Submediterranean distribution, occupying habitats that are slightly warmer, moister, and less seasonal in temperature but more seasonal in precipitation than E. seguieriana, a characteristic species of continental steppes. Using flow cytometry, we demonstrate that the relative genome sizes of E. niciciana and E. seguieriana differ significantly. Additionally, multivariate morphometric analyses of 56 morphological characters indicated clear morphological divergence of the two species. Importantly, we also provide a revised taxonomic treatment including formal nomenclatural changes, an identification key and species descriptions. Our study demonstrates that an integrative approach, combining modern phylogenomic methods with traditional phylogenetic, cytogenetic, environmental and morphological analyses can result in satisfactorily resolved relationships in intricate groups of closely related species. Finally, phylogenetic inference using ITS sequences is still a useful tool for resolving relationships among the taxa at the species level, but the phylogenomic approach based on RADseq data certainly provides better resolution both among and within species.}, } @article {pmid30415022, year = {2019}, author = {Schnittler, M and Horn, K and Kaufmann, R and Rimgailė-Voicik, R and Klahr, A and Bog, M and Fuchs, J and Bennert, HW}, title = {Genetic diversity and hybrid formation in Central European club-mosses (Diphasiastrum, Lycopodiaceae) - New insights from cp microsatellites, two nuclear markers and AFLP.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {181-192}, doi = {10.1016/j.ympev.2018.11.001}, pmid = {30415022}, issn = {1095-9513}, abstract = {In Europe, the genus Diphasiastrum (Lycopodiophyta) forms a reticulate network of six diploid taxa, including three parent species (D. alpinum, D. complanatum and D. tristachyum) and three hybrids (D. × issleri, D. × oellgaardii and D. × zeilleri). It was not clear if the hybrids arose once or repeatedly, if they have reproductive competence and if backcrossing occurs. We addressed these questions by analysing 209 accessions for chloroplast microsatellites (cp), two nuclear markers (introns of the RPB and LFY genes) and AFLP. For D. complanatum we show a sexual life cycle with alternation of generations: the gametophytic DNA amount is half of that of the sporophyte. With the exception of a single accession all hybrids display one of the two parental cp haplotypes; their frequencies do not differ significantly from a 1:1 ratio. Genotypes of nuclear markers are species-specific, displaying 2/4/1 (RPB) and 1/8/1 alleles (LFY) for the three parents mentioned above; all hybrids have one allele from each parent. All three hybrid taxa apparently represent independent F1 crosses. Hybridisation occurs bidirectional; no evidence for recent backcrossing was found. Asexual reproduction via agamospory is at least rare, since AFLP showed all hybrid plants to be different.}, } @article {pmid30414844, year = {2019}, author = {Chang, CN and Singh, AJ and Gross, MK and Kioussi, C}, title = {Requirement of Pitx2 for skeletal muscle homeostasis.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {90-102}, pmid = {30414844}, issn = {1095-564X}, support = {R01 AR054406/AR/NIAMS NIH HHS/United States ; }, abstract = {Skeletal muscle is generated by the successive incorporation of primary (embryonic), secondary (fetal), and tertiary (adult) fibers into muscle. Conditional excision of Pitx2 function by an MCKCre driver resulted in animals with histological and ultrastructural defects in P30 muscles and fibers, respectively. Mutant muscle showed severe reduction in mitochondria and FoxO3-mediated mitophagy. Both oxidative and glycolytic energy metabolism were reduced. Conditional excision was limited to fetal muscle fibers after the G1-G0 transition and resulted in altered MHC, Rac1, MEF2a, and alpha-tubulin expression within these fibers. The onset of excision, monitored by a nuclear reporter gene, was observed as early as E16. Muscle at this stage was already severely malformed, but appeared to recover by P30 by the expansion of adjoining larger fibers. Our studies demonstrate that the homeodomain transcription factor Pitx2 has a postmitotic role in maintaining skeletal muscle integrity and energy homeostasis in fetal muscle fibers.}, } @article {pmid30414454, year = {2018}, author = {Liao, H and Zhong, X and Xu, L and Ma, Q and Wang, Y and Cai, Y and Guo, X}, title = {Quorum-sensing systems trigger catalase expression to reverse the oxyR deletion-mediated VBNC state in Salmonella typhimurium.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.10.004}, pmid = {30414454}, issn = {1769-7123}, abstract = {OxyR is an important regulatory protein that plays a key role in anti-oxygenation, and its deletion causes a special VBNC (Viable But Non-Culturable) state in many bacteria including Salmonella typhimurium. The S. typhimurium in the VBNC state can grow in LB broth but cannot grow on an LB plate unless its concentration is sufficiently high. However, the mechanism that reverses this state is not clear. In this study, conditioned media containing autoinducer collected from the wild type strain can restore the growth of low concentrations of the oxyR mutant strain on LB plates, and S. typhimurium collected from the plate has higher catalase activity than that from the broth, suggesting that a quorum-sensing system can trigger catalase expression to resuscitate the organism from the VBNC state independent of the OxyR regulon. We discovered a novel catalase (STM14_2049, Cat) whose expression is strictly concentration-dependent. The purified Cat protein has obvious catalase activity in vitro and in vivo and can restore the growth of the low concentration oxyR mutant strain. Thus, we believed Cat plays a role in VBNC resuscitation process. By understanding this mechanism, we can further understand the antioxidation and quorum-sensing systems in Salmonella typhimurium.}, } @article {pmid30414343, year = {2019}, author = {Whitlow, KR and Santini, F and Oufiero, CE}, title = {Convergent evolution of locomotor morphology but not performance in gymnotiform swimmers.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {76-88}, doi = {10.1111/jeb.13399}, pmid = {30414343}, issn = {1420-9101}, support = {//Towson Foundation/ ; //Towson University Foundation/ ; }, abstract = {Convergent evolution of a novel locomotor strategy implies that a fitness benefit may be associated with the new gait. Opportunities to study this phenomenon are often constrained by a lack of transitional taxa, but teleost fishes offer examples of extant species across such evolutionary shifts in gait. For instance, one species from Osteoglossiformes and the entire order of Gymnotiformes independently evolved a novel gait, gymnotiform locomotion, where thrust is produced by the undulation of an elongate anal fin. Here, we investigate whether this convergence in gait is also associated with similarities in shape, burst swimming abilities, and/or steady-swimming energetics. Specifically, we measured body and fin morphology of fish within Gymnotiformes and Osteoglossiformes, along with closely related Siluriformes and Cypriniformes, to examine the link between gymnotiform locomotion and morphology in a phylogenetic context. Second, we tested the burst swimming capabilities and oxygen consumption during endurance swimming of a subset of the same gymnotiform, osteoglossiform, and cypriniform species, including "transitional" Osteoglossiformes that exhibit intermediate gaits, to determine whether the evolution of this specialized gait is associated with a change in either of these performance metrics. Our results suggest that convergence on the gymnotiform gait is associated with morphological convergence, but does not constrain a fish's maximum sprinting speeds or their energetic demands during steady swimming.}, } @article {pmid30414330, year = {2019}, author = {Miller, M and Ratz, T and Richardson, J and Smiseth, PT}, title = {Interplay between age-based competitive asymmetries within the brood and direct competition between inbred and outbred offspring in a burying beetle.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {89-99}, doi = {10.1111/jeb.13398}, pmid = {30414330}, issn = {1420-9101}, support = {//University Of Edinburgh/ ; }, abstract = {Theory suggests that intraspecific competition associated with direct competition between inbred and outbred individuals should be an important determinant of the severity of inbreeding depression. The reason is that, if outbred individuals are stronger competitors than inbred ones, direct competition should have a disproportionate effect on the fitness of inbred individuals. However, an individual's competitive ability is not only determined by its inbreeding status but also by competitive asymmetries that are independent of an individual's inbreeding status. When this is the case, such competitive asymmetries may shape the outcome of direct competition between inbred and outbred individuals. Here, we investigate the interface between age-based competitive asymmetries within broods and direct competition between inbred and outbred offspring in the burying beetle Nicrophorus vespilloides. We found that inbred offspring had lower survival than outbred ones confirming that there was inbreeding depression. Furthermore, seniors (older larvae) grew to a larger size and had higher survival than juniors (younger larvae), confirming that there were age-based competitive asymmetries. Nevertheless, there was no evidence that direct competition between inbred and outbred larvae exacerbated inbreeding depression, no evidence that inbreeding depression was more severe in juniors and no evidence that inbred juniors suffered disproportionately due to competition from outbred seniors. Our results suggest that direct competition between inbred and outbred individuals does not necessarily exacerbate inbreeding depression and that inbred individuals are not always more sensitive to poor and stressful conditions than outbred ones.}, } @article {pmid30414283, year = {2018}, author = {Smith, NMA and Wade, C and Allsopp, MH and Harpur, BA and Zayed, A and Rose, SA and Engelstädter, J and Chapman, NC and Yagound, B and Oldroyd, BP}, title = {Strikingly high levels of heterozygosity despite 20 years of inbreeding in a clonal honey bee.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13397}, pmid = {30414283}, issn = {1420-9101}, support = {DP150101985//Australian Research/ ; }, abstract = {Inbreeding (the mating between closely related individuals) often has detrimental effects that are associated with loss of heterozygosity at overdominant loci, and the expression of deleterious recessive alleles. However, determining which loci are detrimental when homozygous, and the extent of their phenotypic effects, remains poorly understood. Here, we utilize a unique inbred population of clonal (thelytokous) honey bees, Apis mellifera capensis, to determine which loci reduce individual fitness when homozygous. This asexual population arose from a single worker ancestor approximately 20 years ago and has persisted for at least 100 generations. Thelytokous parthenogenesis results in a 1/3 of loss of heterozygosity with each generation. Yet, this population retains heterozygosity throughout its genome due to selection against homozygotes. Deep sequencing of one bee from each of the three known sub-lineages of the population revealed that 3766 of 10 884 genes (34%) have retained heterozygosity across all sub-lineages, suggesting that these genes have heterozygote advantage. The maintenance of heterozygosity in the same genes and genomic regions in all three sub-lineages suggests that nearly every chromosome carries genes that show sufficient heterozygote advantage to be selectively detrimental when homozygous.}, } @article {pmid30414183, year = {2019}, author = {Maxwell, CS and Mattox, K and Turissini, DA and Teixeira, MM and Barker, BM and Matute, DR}, title = {Gene exchange between two divergent species of the fungal human pathogen, Coccidioides.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {42-58}, doi = {10.1111/evo.13643}, pmid = {30414183}, issn = {1558-5646}, support = {R01GM121750//National Institute of General Medical Sciences/ ; T32-AI052080//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; }, abstract = {The fungal genus Coccidioides is composed of two species, Coccidioides immitis and Coccidioides posadasii. These two species are the causal agents of coccidioidomycosis, a pulmonary disease also known as valley fever. The two species are thought to have shared genetic material due to gene exchange in spite of their long divergence. To quantify the magnitude of shared ancestry between them, we analyzed the genomes of a population sample from each species. Next, we inferred what is the expected size of shared haplotypes that might be inherited from the last common ancestor of the two species and find a cutoff to find what haplotypes have conclusively been exchanged between species. Finally, we precisely identified the breakpoints of the haplotypes that have crossed the species boundary and measure the allele frequency of each introgression in this sample. We find that introgressions are not uniformly distributed across the genome. Most, but not all, of the introgressions segregate at low frequency. Our results show that divergent species can share alleles, that species boundaries can be porous, and highlight the need for a systematic exploration of gene exchange in fungal species.}, } @article {pmid30413770, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {334}, doi = {10.1038/d41586-018-07356-3}, pmid = {30413770}, issn = {1476-4687}, } @article {pmid30413626, year = {2018}, author = {Bergey, CM and Lopez, M and Harrison, GF and Patin, E and Cohen, JA and Quintana-Murci, L and Barreiro, LB and Perry, GH}, title = {Polygenic adaptation and convergent evolution on growth and cardiac genetic pathways in African and Asian rainforest hunter-gatherers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11256-E11263}, pmid = {30413626}, issn = {1091-6490}, support = {F32 GM125228/GM/NIGMS NIH HHS/United States ; R01 GM115656/GM/NIGMS NIH HHS/United States ; }, abstract = {Different human populations facing similar environmental challenges have sometimes evolved convergent biological adaptations, for example, hypoxia resistance at high altitudes and depigmented skin in northern latitudes on separate continents. The "pygmy" phenotype (small adult body size), characteristic of hunter-gatherer populations inhabiting both African and Asian tropical rainforests, is often highlighted as another case of convergent adaptation in humans. However, the degree to which phenotypic convergence in this polygenic trait is due to convergent versus population-specific genetic changes is unknown. To address this question, we analyzed high-coverage sequence data from the protein-coding portion of the genomes of two pairs of populations: Batwa rainforest hunter-gatherers and neighboring Bakiga agriculturalists from Uganda and Andamanese rainforest hunter-gatherers and Brahmin agriculturalists from India. We observed signatures of convergent positive selection between the rainforest hunter-gatherers across the set of genes with "growth factor binding" functions ([Formula: see text]). Unexpectedly, for the rainforest groups, we also observed convergent and population-specific signatures of positive selection in pathways related to cardiac development (e.g., "cardiac muscle tissue development"; [Formula: see text]). We hypothesize that the growth hormone subresponsiveness likely underlying the adult small body-size phenotype may have led to compensatory changes in cardiac pathways, in which this hormone also plays an essential role. Importantly, in the agriculturalist populations, we did not observe similar patterns of positive selection on sets of genes associated with growth or cardiac development, indicating our results most likely reflect a history of convergent adaptation to the similar ecology of rainforests rather than a more general evolutionary pattern.}, } @article {pmid30413625, year = {2018}, author = {Heck, R and Vuculescu, O and Sørensen, JJ and Zoller, J and Andreasen, MG and Bason, MG and Ejlertsen, P and Elíasson, O and Haikka, P and Laustsen, JS and Nielsen, LL and Mao, A and Müller, R and Napolitano, M and Pedersen, MK and Thorsen, AR and Bergenholtz, C and Calarco, T and Montangero, S and Sherson, JF}, title = {Remote optimization of an ultracold atoms experiment by experts and citizen scientists.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11231-E11237}, pmid = {30413625}, issn = {1091-6490}, abstract = {We introduce a remote interface to control and optimize the experimental production of Bose-Einstein condensates (BECs) and find improved solutions using two distinct implementations. First, a team of theoreticians used a remote version of their dressed chopped random basis optimization algorithm (RedCRAB), and second, a gamified interface allowed 600 citizen scientists from around the world to participate in real-time optimization. Quantitative studies of player search behavior demonstrated that they collectively engage in a combination of local and global searches. This form of multiagent adaptive search prevents premature convergence by the explorative behavior of low-performing players while high-performing players locally refine their solutions. In addition, many successful citizen science games have relied on a problem representation that directly engaged the visual or experiential intuition of the players. Here we demonstrate that citizen scientists can also be successful in an entirely abstract problem visualization. This is encouraging because a much wider range of challenges could potentially be opened to gamification in the future.}, } @article {pmid30413624, year = {2018}, author = {Bray, MS and Lenz, TK and Haynes, JW and Bowman, JC and Petrov, AS and Reddi, AR and Hud, NV and Williams, LD and Glass, JB}, title = {Multiple prebiotic metals mediate translation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12164-12169}, pmid = {30413624}, issn = {1091-6490}, abstract = {Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life's oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O2, high Fe2+, and high Mn2+) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg2+, Fe2+, and Mn2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ or Mn2+ could mediate protein production, and quantified ribosomal metal content. We found that (i) Mg2+, Fe2+, and Mn2+ had strikingly similar effects on rRNA folding; (ii) Fe2+ and Mn2+ can replace Mg2+ as the dominant divalent cation during translation of mRNA to functional protein; and (iii) Fe and Mn associate extensively with the ribosome. Given that the translation system originated and matured when Fe2+ and Mn2+ were abundant, these findings suggest that Fe2+ and Mn2+ played a role in early ribosomal evolution.}, } @article {pmid30413623, year = {2018}, author = {Klusmann, I and Wohlberedt, K and Magerhans, A and Teloni, F and Korbel, JO and Altmeyer, M and Dobbelstein, M}, title = {Chromatin modifiers Mdm2 and RNF2 prevent RNA:DNA hybrids that impair DNA replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11311-E11320}, pmid = {30413623}, issn = {1091-6490}, abstract = {The p53-Mdm2 system is key to tumor suppression. We have recently reported that p53 as well as Mdm2 are capable of supporting DNA replication fork progression. On the other hand, we found that Mdm2 is a modifier of chromatin, modulating polycomb repressor complex (PRC)-driven histone modifications. Here we show that, similar to Mdm2 knockdown, the depletion of PRC members impairs DNA synthesis, as determined in fiber assays. In particular, the ubiquitin ligase and PRC1 component RNF2/Ring1B is required to support DNA replication, similar to Mdm2. Moreover, the Ring finger domain of Mdm2 is not only essential for its ubiquitin ligase activity, but also for proper DNA replication. Strikingly, Mdm2 overexpression can rescue RNF2 depletion with regard to DNA replication fork progression, and vice versa, strongly suggesting that the two ubiquitin ligases perform overlapping functions in this context. H2A overexpression also rescues fork progression upon depletion of Mdm2 or RNF2, but only when the ubiquitination sites K118/K119 are present. Depleting the H2A deubiquitinating enzyme BAP1 reduces the fork rate, suggesting that both ubiquitination and deubiquitination of H2A are required to support fork progression. The depletion of Mdm2 elicits the accumulation of RNA/DNA hybrids, suggesting R-loop formation as a mechanism of impaired DNA replication. Accordingly, RNase H overexpression or the inhibition of the transcription elongation kinase CDK9 each rescues DNA replication upon depletion of Mdm2 or RNF2. Taken together, our results suggest that chromatin modification by Mdm2 and PRC1 ensures smooth DNA replication through the avoidance of R-loop formation.}, } @article {pmid30413622, year = {2018}, author = {Muhlemann, JK and Younts, TLB and Muday, GK}, title = {Flavonols control pollen tube growth and integrity by regulating ROS homeostasis during high-temperature stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11188-E11197}, pmid = {30413622}, issn = {1091-6490}, mesh = {Anthocyanins/genetics/metabolism ; Flavonols/genetics/*metabolism ; Heat-Shock Response/*physiology ; Hot Temperature ; Lycopersicon esculentum/*growth & development ; Pollen/metabolism ; Pollen Tube/*growth & development/*metabolism ; Pollination/physiology ; Reactive Oxygen Species/*metabolism ; Seeds/growth & development/metabolism ; Stress, Physiological/*physiology ; }, abstract = {Plant reproduction requires long-distance growth of a pollen tube to fertilize the female gametophyte. Prior reports suggested that mutations altering synthesis of flavonoids, plant specialized metabolites that include flavonols and anthocyanins, impair pollen development in several species, but the mechanism by which flavonols enhanced fertility was not defined. Here, we used genetic approaches to demonstrate that flavonols enhanced pollen development by reducing the abundance of reactive oxygen species (ROS). We further showed that flavonols reduced high-temperature stress-induced ROS accumulation and inhibition of pollen tube growth. The anthocyanin reduced (are) tomato mutant had reduced flavonol accumulation in pollen grains and tubes. This mutant produced fewer pollen grains and had impaired pollen viability, germination, tube growth, and tube integrity, resulting in reduced seed set. Consistent with flavonols acting as ROS scavengers, are had elevated levels of ROS. The pollen viability, tube growth and integrity defects, and ROS accumulation in are were reversed by genetic complementation. Inhibition of ROS synthesis or scavenging of excess ROS with an exogenous antioxidant treatment also reversed the are phenotypes, indicating that flavonols function by reducing ROS levels. Heat stress resulted in increased ROS in pollen tubes and inhibited tube growth, with more pronounced effects in the are mutant that could be rescued by antioxidant treatment. These results are consistent with increased ROS inhibiting pollen tube growth and with flavonols preventing ROS from reaching damaging levels. These results reveal that flavonol metabolites regulate plant sexual reproduction at both normal and elevated temperatures by maintaining ROS homeostasis.}, } @article {pmid30413621, year = {2018}, author = {Tian, P and Steward, A and Kudva, R and Su, T and Shilling, PJ and Nickson, AA and Hollins, JJ and Beckmann, R and von Heijne, G and Clarke, J and Best, RB}, title = {Folding pathway of an Ig domain is conserved on and off the ribosome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11284-E11293}, pmid = {30413621}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; WT095195//Wellcome Trust/United Kingdom ; }, abstract = {Proteins that fold cotranslationally may do so in a restricted configurational space, due to the volume occupied by the ribosome. How does this environment, coupled with the close proximity of the ribosome, affect the folding pathway of a protein? Previous studies have shown that the cotranslational folding process for many proteins, including small, single domains, is directly affected by the ribosome. Here, we investigate the cotranslational folding of an all-β Ig domain, titin I27. Using an arrest peptide-based assay and structural studies by cryo-EM, we show that I27 folds in the mouth of the ribosome exit tunnel. Simulations that use a kinetic model for the force dependence of escape from arrest accurately predict the fraction of folded protein as a function of length. We used these simulations to probe the folding pathway on and off the ribosome. Our simulations-which also reproduce experiments on mutant forms of I27-show that I27 folds, while still sequestered in the mouth of the ribosome exit tunnel, by essentially the same pathway as free I27, with only subtle shifts of critical contacts from the C to the N terminus.}, } @article {pmid30413620, year = {2018}, author = {Zhu, L and Stein, LR and Kim, D and Ho, K and Yu, GQ and Zhan, L and Larsson, TE and Mucke, L}, title = {Klotho controls the brain-immune system interface in the choroid plexus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11388-E11396}, pmid = {30413620}, issn = {1091-6490}, support = {F32 NS093766/NS/NINDS NIH HHS/United States ; R01 NS088532/NS/NINDS NIH HHS/United States ; }, abstract = {Located within the brain's ventricles, the choroid plexus produces cerebrospinal fluid and forms an important barrier between the central nervous system and the blood. For unknown reasons, the choroid plexus produces high levels of the protein klotho. Here, we show that these levels naturally decline with aging. Depleting klotho selectively from the choroid plexus via targeted viral vector-induced knockout in Klothoflox/flox mice increased the expression of multiple proinflammatory factors and triggered macrophage infiltration of this structure in young mice, simulating changes in unmanipulated old mice. Wild-type mice infected with the same Cre recombinase-expressing virus did not show such alterations. Experimental depletion of klotho from the choroid plexus enhanced microglial activation in the hippocampus after peripheral injection of mice with lipopolysaccharide. In primary cultures, klotho suppressed thioredoxin-interacting protein-dependent activation of the NLRP3 inflammasome in macrophages by enhancing fibroblast growth factor 23 signaling. We conclude that klotho functions as a gatekeeper at the interface between the brain and immune system in the choroid plexus. Klotho depletion in aging or disease may weaken this barrier and promote immune-mediated neuropathogenesis.}, } @article {pmid30413619, year = {2018}, author = {Benson, AR and Abebe, R and Schaub, MT and Jadbabaie, A and Kleinberg, J}, title = {Simplicial closure and higher-order link prediction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11221-E11230}, pmid = {30413619}, issn = {1091-6490}, abstract = {Networks provide a powerful formalism for modeling complex systems by using a model of pairwise interactions. But much of the structure within these systems involves interactions that take place among more than two nodes at once-for example, communication within a group rather than person to person, collaboration among a team rather than a pair of coauthors, or biological interaction between a set of molecules rather than just two. Such higher-order interactions are ubiquitous, but their empirical study has received limited attention, and little is known about possible organizational principles of such structures. Here we study the temporal evolution of 19 datasets with explicit accounting for higher-order interactions. We show that there is a rich variety of structure in our datasets but datasets from the same system types have consistent patterns of higher-order structure. Furthermore, we find that tie strength and edge density are competing positive indicators of higher-order organization, and these trends are consistent across interactions involving differing numbers of nodes. To systematically further the study of theories for such higher-order structures, we propose higher-order link prediction as a benchmark problem to assess models and algorithms that predict higher-order structure. We find a fundamental difference from traditional pairwise link prediction, with a greater role for local rather than long-range information in predicting the appearance of new interactions.}, } @article {pmid30413618, year = {2018}, author = {Zhao, Y and Thornton, JA and Pye, HOT}, title = {Quantitative constraints on autoxidation and dimer formation from direct probing of monoterpene-derived peroxy radical chemistry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12142-12147}, pmid = {30413618}, issn = {1091-6490}, abstract = {Organic peroxy radicals (RO2) are key intermediates in the atmospheric degradation of organic matter and fuel combustion, but to date, few direct studies of specific RO2 in complex reaction systems exist, leading to large gaps in our understanding of their fate. We show, using direct, speciated measurements of a suite of RO2 and gas-phase dimers from O3-initiated oxidation of α-pinene, that ∼150 gaseous dimers (C16-20H24-34O4-13) are primarily formed through RO2 cross-reactions, with a typical rate constant of 0.75-2 × 10-12 cm3 molecule-1 s-1 and a lower-limit dimer formation branching ratio of 4%. These findings imply a gaseous dimer yield that varies strongly with nitric oxide (NO) concentrations, of at least 0.2-2.5% by mole (0.5-6.6% by mass) for conditions typical of forested regions with low to moderate anthropogenic influence (i.e., ≤50-parts per trillion NO). Given their very low volatility, the gaseous C16-20 dimers provide a potentially important organic medium for initial particle formation, and alone can explain 5-60% of α-pinene secondary organic aerosol mass yields measured at atmospherically relevant particle mass loadings. The responses of RO2, dimers, and highly oxygenated multifunctional compounds (HOM) to reacted α-pinene concentration and NO imply that an average ∼20% of primary α-pinene RO2 from OH reaction and 10% from ozonolysis autoxidize at 3-10 s-1 and ≥1 s-1, respectively, confirming both oxidation pathways produce HOM efficiently, even at higher NO concentrations typical of urban areas. Thus, gas-phase dimer formation and RO2 autoxidation are ubiquitous sources of low-volatility organic compounds capable of driving atmospheric particle formation and growth.}, } @article {pmid30413617, year = {2018}, author = {Su, Z and Tang, Y and Ritchey, LE and Tack, DC and Zhu, M and Bevilacqua, PC and Assmann, SM}, title = {Genome-wide RNA structurome reprogramming by acute heat shock globally regulates mRNA abundance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12170-12175}, pmid = {30413617}, issn = {1091-6490}, abstract = {The heat shock response is crucial for organism survival in natural environments. RNA structure is known to influence numerous processes related to gene expression, but there have been few studies on the global RNA structurome as it prevails in vivo. Moreover, how heat shock rapidly affects RNA structure genome-wide in living systems remains unknown. We report here in vivo heat-regulated RNA structuromes. We applied Structure-seq chemical [dimethyl sulfate (DMS)] structure probing to rice (Oryza sativa L.) seedlings with and without 10 min of 42 °C heat shock and obtained structural data on >14,000 mRNAs. We show that RNA secondary structure broadly regulates gene expression in response to heat shock in this essential crop species. Our results indicate significant heat-induced elevation of DMS reactivity in the global transcriptome, revealing RNA unfolding over this biological temperature range. Our parallel Ribo-seq analysis provides no evidence for a correlation between RNA unfolding and heat-induced changes in translation, in contrast to the paradigm established in prokaryotes, wherein melting of RNA thermometers promotes translation. Instead, we find that heat-induced DMS reactivity increases correlate with significant decreases in transcript abundance, as quantified from an RNA-seq time course, indicating that mRNA unfolding promotes transcript degradation. The mechanistic basis for this outcome appears to be mRNA unfolding at both 5' and 3'-UTRs that facilitates access to the RNA degradation machinery. Our results thus reveal unexpected paradigms governing RNA structural changes and the eukaryotic RNA life cycle.}, } @article {pmid30413616, year = {2018}, author = {Jia, PF and Xue, Y and Li, HJ and Yang, WC}, title = {Golgi-localized LOT regulates trans-Golgi network biogenesis and pollen tube growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12307-12312}, pmid = {30413616}, issn = {1091-6490}, abstract = {The trans-Golgi network (TGN) is an essential tubular-vesicular organelle derived from the Golgi and functions as an independent sorting and trafficking hub within the cell. However, the molecular regulation of TGN biogenesis remains enigmatic. Here we identified an Arabidopsis mutant loss of TGN (lot) that is defective in TGN formation and sterile due to impaired pollen tube growth in the style. The mutation leads to overstacking of the Golgi cisternae and significant reduction in the number of TGNs and vesicles surrounding the Golgi in pollen, which is corroborated by the dispersed cytosolic distribution of TGN-localized proteins. Consistently, deposition of extracellular pectin and plasma membrane localization of kinases and phosphoinositide species are also impaired. Subcellular localization analysis suggests that LOT is localized on the periphery of the Golgi cisternae, but the mutation does not affect the localization of Golgi-resident proteins. Furthermore, the yeast complementation result suggests that LOT could functionally act as a component of the guanine nucleotide exchange factor (GEF) complex of small Rab GTPase Ypt6. Taken together, these findings suggest that LOT is a critical player for TGN biogenesis in the plant lineage.}, } @article {pmid30413615, year = {2018}, author = {Mehta, M and Brzostek, J and Chen, EW and Tung, DWH and Chen, S and Sankaran, S and Yap, J and Rybakin, V and Gascoigne, NRJ}, title = {Themis-associated phosphatase activity controls signaling in T cell development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11331-E11340}, pmid = {30413615}, issn = {1091-6490}, abstract = {Thymocyte-expressed molecule involved in selection (Themis) has been shown to be important for T cell selection by setting the threshold for positive versus negative selection. Themis interacts with the protein tyrosine phosphatase (PTP) Src-homology domain containing phosphatase-1 (Shp1), a negative regulator of the T cell receptor (TCR) signaling cascade. However, how Themis regulates Shp1 is still not clear. Here, using a very sensitive phosphatase assay on ex vivo thymocytes, we have found that Themis enhances Shp1 phosphatase activity by increasing its phosphorylation. This positive regulation of Shp1 activity by Themis is found in thymocytes, but not in peripheral T cells. Shp1 activity is modulated by different affinity peptide MHC ligand binding in thymocytes. Themis is also associated with phosphatase activity, due to its constitutive interaction with Shp1. In the absence of Shp1 in thymocytes, Themis interacts with Shp2, which leads to almost normal thymic development in Shp1 conditional knockout (cKO) mice. Double deletion of both Themis and Shp1 leads to a thymic phenotype similar to that of Themis KO. These findings demonstrate unequivocally that Themis positively regulates Shp1 phosphatase activity in TCR-mediated signaling in developing thymocytes.}, } @article {pmid30413190, year = {2018}, author = {Asmare, B and Taddele, M and Berihun, S and Wagnew, F}, title = {Nutritional status and correlation with academic performance among primary school children, northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {805}, pmid = {30413190}, issn = {1756-0500}, abstract = {OBJECTIVE: This study aimed to determine the association between nutritional status and academic performance among primary school children in Debre Markos Town, northwest Ethiopia, 2017.

RESULTS: The prevalence of stunting, underweight and wasting were 27.5% (95% CI 23.2-31.9%), 20.4% (95% CI 16.5-24.3%) and 8.7% (95% CI 6.2-11.5%), correspondingly. The low level of educational performance was significantly higher (p < 0.05) among the stunted, underweight and wasted children than that of the normal children. In multivariable logistic regression, age of the child (Adjusted Odds Ratio (AOR) = 0.177, 95% CI 0.07, 0.4), monthly income less < 1000.00 birr (AOR = 0.05, 95% Cl 0.02, 0.15), stunted children (AOR = 0.21, 95% CI 0.10, 0.43) and under-weight (AOR = 0.63, 95% CI 0.26, 0.84) were associated with academic performance. This study revealed that indicators of undernutrition were prevalent among school-age children. Thus, collaboration between the health and education sectors is required to alleviate the problem.}, } @article {pmid30413183, year = {2018}, author = {He, P and Wang, X and Zhang, X and Jiang, Y and Tian, W and Zhang, X and Li, Y and Sun, Y and Xie, J and Ni, J and He, G and Sang, X}, title = {Short and narrow flag leaf1, a GATA zinc finger domain-containing protein, regulates flag leaf size in rice (Oryza sativa).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {273}, pmid = {30413183}, issn = {1471-2229}, support = {2016YFD0100501//Ministry of Science and Technology of the People's Republic of China/ ; 2016ZX08001-002//National Transgenic Major Program of China/ ; cstc2016shms-ztzx80007//Chongqing Science and Technology Innovation Special Project/ ; cstc2017shms-xdny80057//Chongqing Science and Technology Innovation Special Project/ ; cstc2015jcyjA80008//Chongqing Research Program of Basic Research and Frontier Technology/ ; XDJK2015D031//Fundamental Research Funds for the Central Universities/ ; }, mesh = {*Alternative Splicing ; Cell Nucleus/metabolism ; Chromosome Mapping ; Edible Grain/genetics/growth & development ; GATA Transcription Factors/genetics/*metabolism ; Genes, Reporter ; Mutation ; Oryza/*genetics/growth & development ; Phenotype ; Plant Leaves/genetics/growth & development ; Plant Proteins/genetics/metabolism ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; Zinc Fingers ; }, abstract = {BACKGROUND: The flag leaf of rice (Oryza sativa L.) is an important determinant of plant type characteristics and grain yield. Identification of flag leaf mutants of rice is crucial to elucidate the molecular mechanism of flag-leaf development, and for exploitation of rice germplasm resources.

RESULTS: In this study, we describe a mutant designated short and narrow flag leaf 1 (snfl1). Histological analysis showed that the length of epidermal cells and number of longitudinal veins were decreased in the flag leaf of the snfl1 mutant. Map-based cloning indicated that a member of the GATA family of transcription factors is a candidate gene for SNFL1. A single-nucleotide transition at the last base in the single intron of snfl1 led to variation in alternative splicing and early termination of translation. Complemented transgenic plants harbouring the candidate SNFL1 gene rescued the snfl1 mutant. Analysis of RT-PCR and the SNFL1 promoter by means of a GUS fusion expression assay showed that abundance of SNFL1 transcripts was higher in the culm, leaf sheath, and root. Expression of the SNFL1-GFP fusion protein in rice protoplasts showed that SNFL1 was localized in nucleus.

CONCLUSIONS: We conclude that SNFL1 is an important regulator of leaf development, the identification of which might have important implications for future research on GATA transcription factors.}, } @article {pmid30413148, year = {2018}, author = {Caterino, MS and Langton-Myers, SS}, title = {Long-term population persistence of flightless weevils (Eurhoptus pyriformis) across old- and second-growth forests patches in southern Appalachia.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {165}, pmid = {30413148}, issn = {1471-2148}, mesh = {Animals ; Appalachian Region ; Bayes Theorem ; Biodiversity ; *Flight, Animal ; *Forests ; Phylogeny ; Phylogeography ; Population Dynamics ; Weevils/classification/genetics/*growth & development ; }, abstract = {BACKGROUND: Southern Appalachian forests are dominated by second-growth vegetation following decades of intensive forestry and agricultural use, although some old-growth patches remain. While it's been shown that second-growth areas may exhibit comparable species richness to old-growth in the area, the extent to which populations of arthropods in second-growth areas have persisted vs. recolonized from other areas remains unexamined. The implications for conservation of both classes of forest are significant. Here we analyze population diversity and relatedness across five old-growth and five second-growth populations of flightless, leaf litter-inhabiting beetles in the genus Eurhoptus (Coleoptera: Curculionidae: Cryptorhynchinae). Our main goal is asking whether second-growth areas show diminished diversity and/or signals of recolonization from old-growth sources.

RESULTS: Population genetic and phylogenetic analyses do not reveal any consistent differences in diversity between the old-growth and second-growth populations examined. Some second-growth populations retain substantial genetic diversity, while some old-growth populations appear relatively depauperate. There is no phylogenetic indication that second-growth populations have recolonized from old-growth source populations.

CONCLUSIONS: Most populations contain substantial and unique genetic diversity indicating long-term persistence in the majority of sites. The results support substantial resilience in second-growth populations, though the geographic scale of sampling may have hindered detection of recolonization patterns. Broad scale phylogeographic patterns reveal a deep break across the French Broad River basin, as has been reported in several other taxa of limited dispersal abilities. In Eurhoptus this break dates to ~ 2-6 Ma ago, on the older end of the range of previously estimated dates.}, } @article {pmid30413147, year = {2018}, author = {Wu, SD and Zhang, LJ and Lin, L and Yu, SX and Chen, ZD and Wang, W}, title = {Insights into the historical assembly of global dryland floras: the diversification of Zygophyllaceae.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {166}, pmid = {30413147}, issn = {1471-2148}, mesh = {Africa ; Asia ; Australia ; *Ecosystem ; Geography ; *Internationality ; Phylogeny ; Time Factors ; Zygophyllaceae/*classification ; }, abstract = {BACKGROUND: Drylands cover nearly 41% of Earth's land surface and face a high risk of degradation worldwide. However, the actual timeframe during which dryland floras rose on a global scale remains unknown. Zygophyllaceae, an important characteristic component of dryland floras worldwide, offers an ideal model group to investigate the diversification of dryland floras. Here, we used an integration of the phylogenetic, molecular dating, biogeographic, and diversification methods to investigate the timing and patterns of lineage accumulation for Zygophyllaceae overall and regionally. We then incorporated the data from other dominant components of dryland floras in different continents to investigate the historical construction of dryland floras on a global scale.

RESULTS: We provide the most comprehensive phylogenetic tree for Zygophyllaceae so far based on four plastid and nuclear markers. Detailed analyses indicate that Zygophyllaceae colonized Africa, Asia, Australia, and the New World at different periods, sometimes multiple times, but Zygophyllaceae lineages in the four regions all experienced a rapid accumulation beginning at the mid-late Miocene (~ 15-10 Ma). Other eleven essential elements of dryland floras become differentiated at the same time.

CONCLUSIONS: Our results suggest that the rise of global dryland floras is near-synchronous and began at the mid-late Miocene, possibly resulting from the mid-Miocene global cooling and regional orogenetic and climate changes. The mid-late Miocene is an essential period for the assembly and evolution of global dryland floras.}, } @article {pmid30412828, year = {2018}, author = {Ruhland, BR and Reniere, ML}, title = {Sense and sensor ability: redox-responsive regulators in Listeria monocytogenes.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {20-25}, doi = {10.1016/j.mib.2018.10.006}, pmid = {30412828}, issn = {1879-0364}, support = {R01 AI132356/AI/NIAID NIH HHS/United States ; }, abstract = {Listeria monocytogenes (Lm) is a Gram-positive bacterium that thrives in nature as a saprophyte and in the mammalian host as an intracellular pathogen. Both environments pose potential danger in the form of redox stress. In addition, endogenous reactive oxygen species (ROS) are continuously generated as by-products of aerobic metabolism. Redox stress from ROS can damage proteins, lipids, and DNA, making it highly advantageous for bacteria to evolve mechanisms to sense and detoxify ROS. This review focuses on the five redox-responsive regulators in Lm: OhrR (to sense organic hydroperoxides), PerR (peroxides), Rex (NAD+/NADH homeostasis), SpxA1/2 (disulfide stress), and PrfA (redox stress during infection).}, } @article {pmid30412702, year = {2019}, author = {Minor, PJ and Clarke, DN and Andrade López, JM and Fritzenwanker, JH and Gray, J and Lowe, CJ}, title = {I-SceI Meganuclease-mediated transgenesis in the acorn worm, Saccoglossus kowalevskii.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {8-15}, doi = {10.1016/j.ydbio.2018.10.022}, pmid = {30412702}, issn = {1095-564X}, support = {F32 NS098658/NS/NINDS NIH HHS/United States ; R01 HD073104/HD/NICHD NIH HHS/United States ; }, abstract = {Hemichordates are a phylum of marine invertebrate deuterostomes that are closely related to chordates, and represent one of the most promising models to provide insights into early deuterostome evolution. The genome of the hemichordate, Saccoglossus kowalevskii, reveals an extensive set of non-coding elements conserved across all three deuterostome phyla. Functional characterization and cross-phyla comparisons of these putative regulatory elements will enable a better understanding of enhancer evolution, and subsequently how changes in gene regulation give rise to morphological innovation. Here, we describe an efficient method of transgenesis for the characterization of non-coding elements in S. kowalevskii. We first test the capacity of an I-SceI transgenesis system to drive ubiquitous or regionalized gene expression, and to label specific cell types. Finally, we identified a minimal promoter that can be used to test the capacity of putative enhancers in S. kowalevskii. This work demonstrates that this I-SceI transgenesis technique, when coupled with an understanding of chromatin accessibility, can be a powerful tool for studying how evolutionary changes in gene regulatory mechanisms contributed to the diversification of body plans in deuterostomes.}, } @article {pmid30411517, year = {2018}, author = {Khullar, S and Sudhakara Reddy, M}, title = {Cadmium and arsenic responses in the ectomycorrhizal fungus Laccaria bicolor: glutathione metabolism and its role in metal(loid) homeostasis.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12712}, pmid = {30411517}, issn = {1758-2229}, support = {BT/PR8339/BCE/8/1045/2013//Department of Biotechnology , Ministry of Science and Technology/ ; }, abstract = {Ectomycorrhizal fungi play an important role in protecting their host plant from metal(loid) stresses by synthesizing various thiol rich compounds like metallothioneins and glutathione. We investigated the effect of cadmium (Cd) and arsenic (As) stress with a specific interest on glutathione (GSH) in the ectomycorrhizal fungus Laccaria bicolor. The total GSH levels inside the cell were significantly increased with increase in external metal(loid) stress. An analysis of the transcript levels of genes responsible for GSH synthesis, γ-glutamylcysteine synthetase (Lbγ-GCS) and glutathione synthetase (LbGS), using qPCR revealed that expression of both genes increased as a function of external metal(loid) concentration. The enzyme activity of both Lbγ-GCS and LbGS were increased with increase in external Cd and As concentration. Further, the functional role of Lbγ-GCS and LbGS genes in response to Cd and As stress was studied using their respective yeast mutant strains gsh1 Δ and gsh2 Δ . The mutant strains successfully expressed the two genes resulting in wild-type phenotype restoration of Cd and As tolerance. From these results, it was concluded that GSH act as a core component in the mycorrhizal defence system under Cd and As stress for metal(loid) homeostasis and detoxification.}, } @article {pmid30411512, year = {2018}, author = {Nanayakkara, BS and O'Brien, CL and Gordon, DM}, title = {Diversity and distribution of Klebsiella capsules in Escherichia coli.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12710}, pmid = {30411512}, issn = {1758-2229}, support = {LP120100327//Australian Research Council/ ; //Water Research Australia/ ; }, abstract = {E. coli strains responsible for elevated counts (blooms) in freshwater reservoirs in Australia carry a capsule originating from Klebsiella. The occurrence of Klebsiella capsules in E. coli was about 7% overall and 23 different capsule types were detected. Capsules were observed in strains from phylogroups A, B1 and C, but were absent from phylogroup B2, D, E and F strains. In general, few A, B1 or C lineages were capsule-positive, but when a lineage was encapsulated multiple different capsule types were present. All Klebsiella capsule-positive strains were of serogroups O8, O9 and O89. Regardless of the phylogroup, O9 strains were more likely to be capsule-positive than O8 strains. Given the sequence similarity, it appears that both the capsule region and the O-antigen gene region are transferred to E. coli from Klebsiella as a single block via horizontal gene transfer events. Pan genome analysis indicated that there were only modest differences between encapsulated and non-encapsulated strains belonging to phylogroup A. The possession of a Klebsiella capsule, but not the type of capsule, is likely a key determinant of the bloom status of a strain.}, } @article {pmid30411474, year = {2018}, author = {Lorenz, A and Preuße, M and Bruchmann, S and Pawar, V and Grahl, N and Pils, MC and Nolan, LM and Filloux, A and Weiss, S and Häussler, S}, title = {Importance of flagella in acute and chronic Pseudomonas aeruginosa infections.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14468}, pmid = {30411474}, issn = {1462-2920}, support = {IRTG 1273//Deutsche Forschungsgemeinschaft/ ; INDIGO-IPP2-060//INNO INDIGO Partnership Program/ ; //Seventh Framework Programme/ ; }, abstract = {Pseudomonas aeruginosa is an environmental microorganism and a causative agent of diverse acute and chronic, biofilm-associated infections. Advancing research-based knowledge on its adaptation to conditions within the human host is bound to reveal novel strategies and targets for therapeutic intervention. Here, we investigated the traits that P. aeruginosa PA14 as well as a virulence attenuated ΔlasR mutant need to survive in selected murine infection models. Experimentally, the genetic programs that the bacteria use to adapt to biofilm-associated versus acute infections were dissected by passaging transposon mutant libraries through mouse lungs (acute) or mouse tumours (biofilm-infection). Adaptive metabolic changes of P. aeruginosa were generally required during both infection processes. Counter-selection against flagella expression was observed during acute lung infections. Obviously, avoidance of flagella-mediated activation of host immunity is advantageous for the wildtype bacteria. For the ΔlasR mutant, loss of flagella did not confer a selective advantage. Apparently, other pathogenesis mechanisms are active in this virulence attenuated strain. In contrast, the infective process of P. aeruginosa in the chronic biofilm model apparently required expression of flagellin. Together, our findings imply that the host immune reactions against the infectious agent are very decisive for acuteness and duration of the infectious disease. They direct disease outcome.}, } @article {pmid30411473, year = {2019}, author = {Ortega-Arbulú, AS and Pichler, M and Vuillemin, A and Orsi, WD}, title = {Effects of organic matter and low oxygen on the mycobenthos in a coastal lagoon.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {374-388}, doi = {10.1111/1462-2920.14469}, pmid = {30411473}, issn = {1462-2920}, support = {//Ludwig-Maximilians Universität München Junior Researcher Fund/ ; }, abstract = {Fungi living in sediments ('mycobenthos') are hypothesized to play a role in the degradation of organic matter deposited at the land-sea interface, but the environmental factors influencing the mycobenthos are poorly understood. We used mock community calibrated Illumina sequencing to show that the mycobenthos community structure in a coastal lagoon was significantly changed after exposure to a lignocellulose extract and subsequent development of benthic anoxia over a relatively short (10 h) incubation. Saprotrophic taxa dominated and were selected for under benthic anoxia, specifically Aquamyces (Chytridiomycota) and Orbilia (Ascomycota), implicating these genera as important benthic saprotrophs. Protein encoding genes involved in energy and biomass production from Fungi and the fungal-analogue group Labyrinthulomycetes had the highest increase in expression with the added organic matter compared with all other groups, indicating that lignocellulose stimulates metabolic activity in the mycobenthos. Flavobacteria dominated the active bacterial community that grew rapidly with the lignocellulose extract and crashed sharply upon O2 depletion. Our findings indicate that the diversity, activity and trophic potential of the mycobenthos changes rapidly in response to organic matter and decreasing O2 concentrations, which together with heterotrophic Flavobacteria, undergo 'boom and bust' dynamics during lignocellulose degradation in estuarine ecosystems.}, } @article {pmid30411469, year = {2018}, author = {Corona, F and Martínez, JL and Nikel, PI}, title = {The global regulator Crc orchestrates the metabolic robustness underlying oxidative stress resistance in Pseudomonas aeruginosa.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14471}, pmid = {30411469}, issn = {1462-2920}, support = {B2017/BMD-3691//Autonomous Community of Madrid/ ; 8021-00039B//Det Frie Forskningsråd/ ; RD16/0016/0011//Instituto de Salud Carlos III/ ; BIO2017-83128-R//Spanish Ministry of Economy and Competitiveness/ ; NNF10CC1016517//The Novo Nordisk Foundation/ ; }, abstract = {The remarkable metabolic versatility of bacteria of the genus Pseudomonas enable their survival across very diverse environmental conditions. P. aeruginosa, one of the most relevant opportunistic pathogens, is a prime example of this adaptability. The interplay between regulatory networks that mediate these metabolic and physiological features is just starting to be explored in detail. Carbon catabolite repression, governed by the Crc protein, controls the availability of several enzymes and transporters involved in the assimilation of secondary carbon sources. Yet, the regulation exerted by Crc on redox metabolism of P. aeruginosa (hence, on the overall physiology) had hitherto been unexplored. In this study, we address the intimate connection between carbon catabolite repression and metabolic robustness of P. aeruginosa PAO1. In particular, we explored the interplay between oxidative stress, metabolic rearrangements in central carbon metabolism and the cellular redox state. By adopting a combination of quantitative physiology experiments, multiomic analyses, transcriptional patterns of key genes, measurement of metabolic activities in vitro and direct quantification of redox balances both in the wild-type strain and in an isogenic Δcrc derivative, we demonstrate that Crc orchestrates the overall response of P. aeruginosa to oxidative stress via reshaping of the core metabolic architecture in this bacterium.}, } @article {pmid30411468, year = {2019}, author = {Birrer, SC and Dafforn, KA and Sun, MY and Williams, RBH and Potts, J and Scanes, P and Kelaher, BP and Simpson, SL and Kjelleberg, S and Swarup, S and Steinberg, P and Johnston, EL}, title = {Using meta-omics of contaminated sediments to monitor changes in pathways relevant to climate regulation.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {389-401}, doi = {10.1111/1462-2920.14470}, pmid = {30411468}, issn = {1462-2920}, support = {LP130100364//Australian Research Council/ ; }, abstract = {Microbially mediated biogeochemical processes are crucial for climate regulation and may be disrupted by anthropogenic contaminants. To better manage contaminants, we need tools that make real-time causal links between stressors and altered microbial functions, and the potential consequences for ecosystem services such as climate regulation. In a manipulative field experiment, we used metatranscriptomics to investigate the impact of excess organic enrichment and metal contamination on the gene expression of nitrogen and sulfur metabolisms in coastal sediments. Our gene expression data suggest that excess organic enrichment results in (i) higher transcript levels of genes involved in the production of toxic ammonia and hydrogen sulfide and (ii) lower transcript levels associated with the degradation of a greenhouse gas (nitrous oxide). However, metal contamination did not have any significant impact on gene expression. We reveal the genetic mechanisms that may lead to altered productivity and greenhouse gas production in coastal sediments due to anthropogenic contaminants. Our data highlight the applicability of metatranscriptomics as a management tool that provides an immense breadth of information and can identify potentially impacted process measurements that need further investigation.}, } @article {pmid30411346, year = {2019}, author = {Nordén, KK and Faber, JW and Babarović, F and Stubbs, TL and Selly, T and Schiffbauer, JD and Peharec Štefanić, P and Mayr, G and Smithwick, FM and Vinther, J}, title = {Melanosome diversity and convergence in the evolution of iridescent avian feathers-Implications for paleocolor reconstruction.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {15-27}, doi = {10.1111/evo.13641}, pmid = {30411346}, issn = {1558-5646}, support = {PA-UB201506//The Palaeontological Association/ ; W245-12//Waitts Foundation/ ; NE/L002434/1//Natural Environment Research Council/ ; W245-12//National Geographic Society/ ; }, abstract = {Some of the most varied colors in the natural world are created by iridescent nanostructures in bird feathers, formed by layers of melanin-containing melanosomes. The morphology of melanosomes in iridescent feathers is known to vary, but the extent of this diversity, and when it evolved, is unknown. We use scanning electron microscopy to quantify the diversity of melanosome morphology in iridescent feathers from 97 extant bird species, covering 11 orders. In addition, we assess melanosome morphology in two Eocene birds, which are the stem lineages of groups that respectively exhibit hollow and flat melanosomes today. We find that iridescent feathers contain the most varied melanosome morphologies of all types of bird coloration sampled to date. Using our extended dataset, we predict iridescence in an early Eocene trogon (cf. Primotrogon) but not in the early Eocene swift Scaniacypselus, and neither exhibit the derived melanosome morphologies seen in their modern relatives. Our findings confirm that iridescence is a labile trait that has evolved convergently in several lineages extending down to paravian theropods. The dataset provides a framework to detect iridescence with more confidence in fossil taxa based on melanosome morphology.}, } @article {pmid30411338, year = {2018}, author = {Bruns, EL and Miller, I and Hood, ME and Carasso, V and Antonovics, J}, title = {The role of infectious disease in the evolution of females: Evidence from anther-smut disease on a gynodioecious alpine carnation.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13640}, pmid = {30411338}, issn = {1558-5646}, support = {1115765//Division of Environmental Biology/ ; 1115899//Division of Environmental Biology/ ; }, abstract = {In flowering plants, the evolution of females is widely hypothesized to be the first step in the evolutionary pathway to separate male and female sexes, or dioecy. Natural enemies have the potential to drive this evolution if they preferentially attack hermaphrodites over females. We studied sex-based differences in exposure to anther-smut (Microbotryum), a sterilizing pollinator-transmitted disease, in Dianthus pavonius, a gynodioecious perennial herb. We found that within a heavily diseased population, females consistently had lower levels of Microbotryum spore deposition relative to hermaphrodites and that this difference was driven by rapid floral closing in females following successful pollination. We further show that this protective closing behavior is frequency dependent; females close faster when they are rare. These results indicate that anther-smut disease is an important source of selection for females, especially since we found in a common garden experiment no evidence that females have any inherent fecundity advantages over hermaphrodites. Finally, we show that among populations, those where anther-smut is present have a significantly higher frequency of females than those where the disease is absent. Taken together our results indicate that anther-smut disease is likely an important biotic factor driving the evolution and maintenance of females in this gynodioecious species.}, } @article {pmid30411337, year = {2019}, author = {Caruso, CM and Eisen, KE and Martin, RA and Sletvold, N}, title = {A meta-analysis of the agents of selection on floral traits.}, journal = {Evolution; international journal of organic evolution}, volume = {73}, number = {1}, pages = {4-14}, doi = {10.1111/evo.13639}, pmid = {30411337}, issn = {1558-5646}, support = {EF-0905606//National Evolutionary Synthesis Center/ ; DGE-1650441//Division of Graduate Education/ ; Discovery Grant Awarded to CM Caruso//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Floral traits are hypothesized to evolve primarily in response to selection by pollinators. However, selection can also be mediated by other environmental factors. To understand the relative importance of pollinator-mediated selection and its variation among trait and pollinator types, we analyzed directional selection gradients on floral traits from experiments that manipulated the environment to identify agents of selection. Pollinator-mediated selection was stronger than selection by other biotic factors (e.g., herbivores), but similar in strength to selection by abiotic factors (e.g., soil water), providing partial support for the hypothesis that floral traits evolve primarily in response to pollinators. Pollinator-mediated selection was stronger on pollination efficiency traits than on other trait types, as expected if efficiency traits affect fitness via interactions with pollinators, but other trait types also affect fitness via other environmental factors. In addition to varying among trait types, pollinator-mediated selection varied among pollinator taxa: selection was stronger when bees, long-tongued flies, or birds were the primary visitors than when the primary visitors were Lepidoptera or multiple animal taxa. Finally, reducing pollinator access to flowers had a relatively small effect on selection on floral traits, suggesting that anthropogenic declines in pollinator populations would initially have modest effects on floral evolution.}, } @article {pmid30410762, year = {2018}, author = {Humphreys, M}, title = {The influenza of 1918: Evolutionary perspectives in a historical context.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {219-229}, pmid = {30410762}, issn = {2050-6201}, abstract = {The 1918 influenza pandemic was the deadliest in known human history. It spread globally to the most isolated of human communities, causing clinical disease in a third of the world's population, and infecting nearly every human alive at the time. Determination of mortality numbers is complicated by weak contemporary surveillance in the developing world, but recent estimates put the death toll at 50 million or even higher. This outbreak is of great interest to modern day epidemiologists, virologists, global health researchers and evolutionary biologists. They ask: Where did it come from? And if it happened once, could it happen again? Understanding how such a virulent epidemic emerged and spread offers hope for prevention and strategies of response. This review uses historical methodology and evolutionary perspectives to revisit the 1918 outbreak. Using the American military experience as a case study, it investigates the emergence of virulence in 1918 by focusing on key susceptibility factors that favored both the influenza virus and the subsequent pneumococcal invasion that took so many lives. This article explores the history of the epidemic and contemporary measures against it, surveys modern research on the virus, and considers what aspects of 1918 human and animal ecology most contributed to the emergence of this pandemic.}, } @article {pmid30410642, year = {2018}, author = {Pinto, C and Sousa, S and Froufe, H and Egas, C and Clément, C and Fontaine, F and Gomes, AC}, title = {Draft genome sequence of Bacillus amyloliquefaciens subsp. plantarum strain Fito_F321, an endophyte microorganism from Vitis vinifera with biocontrol potential.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {30}, pmid = {30410642}, issn = {1944-3277}, abstract = {Bacillus amyloliquefaciens subsp. plantarum strain Fito_F321 is a naturally occurring strain in vineyard, with the ability to colonise grapevine and which unveils a naturally antagonistic potential against phytopathogens of grapevine, including those responsible for the Botryosphaeria dieback, a GTD disease. Herein we report the draft genome sequence of B. amyloliquefaciens subsp. plantarum Fito_F321, isolated from the leaf of Vitis vinifera cv. Merlot at Bairrada appellation (Cantanhede, Portugal). The genome size is 3,856,229 bp, with a GC content of 46.54% that contains 3697 protein-coding genes, 86 tRNA coding genes and 5 rRNA genes. The draft genome of strain Fito_F321 allowed to predict a set of bioactive compounds as bacillaene, difficidin, macrolactin, surfactin and fengycin that due to their antimicrobial activity are hypothesized to be of utmost importance for biocontrol of grapevine diseases.}, } @article {pmid30410125, year = {2018}, author = {Kossin, JP}, title = {Author Correction: A global slowdown of tropical-cyclone translation speed.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {E11-E16}, doi = {10.1038/s41586-018-0585-1}, pmid = {30410125}, issn = {1476-4687}, abstract = {In this Letter, two errors in the methodology are corrected, leading to changes in Figs. 1-3 and Extended Data Figs. 1 and 2, although the essential results are not affected. The original Letter has been corrected online.}, } @article {pmid30410124, year = {2018}, author = {Seehawer, M and Heinzmann, F and D'Artista, L and Harbig, J and Roux, PF and Hoenicke, L and Dang, H and Klotz, S and Robinson, L and Doré, G and Rozenblum, N and Kang, TW and Chawla, R and Buch, T and Vucur, M and Roth, M and Zuber, J and Luedde, T and Sipos, B and Longerich, T and Heikenwälder, M and Wang, XW and Bischof, O and Zender, L}, title = {Author Correction: Necroptosis microenvironment directs lineage commitment in liver cancer.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {E9}, doi = {10.1038/s41586-018-0723-9}, pmid = {30410124}, issn = {1476-4687}, abstract = {In this Article, the pCaMIN construct consisted of 'mouse MYC and mouse NrasG12V' instead of 'mouse Myc and human NRASG12V; and the pCAMIA construct consisted of 'mouse Myc and human AKT1' instead of 'mouse Myc and Akt1' this has been corrected online.}, } @article {pmid30410104, year = {2018}, author = {Bayvel, P}, title = {Kuen Charles Kao (1933-2018).}, journal = {Nature}, volume = {563}, number = {7731}, pages = {326}, doi = {10.1038/d41586-018-07355-4}, pmid = {30410104}, issn = {1476-4687}, } @article {pmid30410103, year = {2018}, author = {Castelvecchi, D}, title = {The forgotten quantum pioneer who turned wartime spy.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {320-321}, doi = {10.1038/d41586-018-07267-3}, pmid = {30410103}, issn = {1476-4687}, } @article {pmid30410102, year = {2018}, author = {Spinney, L}, title = {Ancient cities rescued from rubble, bit by bit.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {321-322}, doi = {10.1038/d41586-018-07189-0}, pmid = {30410102}, issn = {1476-4687}, } @article {pmid30410089, year = {2018}, author = {Goldstein, T and Anthony, SJ and Gbakima, A and Bird, BH and Bangura, J and Tremeau-Bravard, A and Belaganahalli, MN and Wells, HL and Dhanota, JK and Liang, E and Grodus, M and Jangra, RK and DeJesus, VA and Lasso, G and Smith, BR and Jambai, A and Kamara, BO and Kamara, S and Bangura, W and Monagin, C and Shapira, S and Johnson, CK and Saylors, K and Rubin, EM and Chandran, K and Lipkin, WI and Mazet, JAK}, title = {Author Correction: The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1486}, doi = {10.1038/s41564-018-0315-3}, pmid = {30410089}, issn = {2058-5276}, abstract = {In the version of this Article originally published, the bat species for 12 individuals were incorrectly identified in Supplementary Table 1 and 2. After resequencing the MT-CytB and MT-CO1 segments and reviewing the data, the authors have corrected the errors for these 12 animals. In the amended version of the Supplementary Information, Supplementary Tables 1 and 2 have been replaced to include the corrected host species information. None of the 12 bats affected were positive for the Bombali virus, and the conclusions of the study are therefore unchanged.}, } @article {pmid30410022, year = {2018}, author = {Goymer, P}, title = {Evolutionary puppets.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1834-1835}, doi = {10.1038/s41559-018-0726-9}, pmid = {30410022}, issn = {2397-334X}, } @article {pmid30409886, year = {2018}, author = {Forte, BL}, title = {Finding peace with pencil.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {714}, doi = {10.1126/science.362.6415.714}, pmid = {30409886}, issn = {1095-9203}, } @article {pmid30409885, year = {2018}, author = {Shen, H and Fallas, JA and Lynch, E and Sheffler, W and Parry, B and Jannetty, N and Decarreau, J and Wagenbach, M and Vicente, JJ and Chen, J and Wang, L and Dowling, Q and Oberdorfer, G and Stewart, L and Wordeman, L and De Yoreo, J and Jacobs-Wagner, C and Kollman, J and Baker, D}, title = {De novo design of self-assembling helical protein filaments.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {705-709}, doi = {10.1126/science.aau3775}, pmid = {30409885}, issn = {1095-9203}, support = {R01 GM069429/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {We describe a general computational approach to designing self-assembling helical filaments from monomeric proteins and use this approach to design proteins that assemble into micrometer-scale filaments with a wide range of geometries in vivo and in vitro. Cryo-electron microscopy structures of six designs are close to the computational design models. The filament building blocks are idealized repeat proteins, and thus the diameter of the filaments can be systematically tuned by varying the number of repeat units. The assembly and disassembly of the filaments can be controlled by engineered anchor and capping units built from monomers lacking one of the interaction surfaces. The ability to generate dynamic, highly ordered structures that span micrometers from protein monomers opens up possibilities for the fabrication of new multiscale metamaterials.}, } @article {pmid30409884, year = {2018}, author = {Theisen, DJ and Davidson, JT and Briseño, CG and Gargaro, M and Lauron, EJ and Wang, Q and Desai, P and Durai, V and Bagadia, P and Brickner, JR and Beatty, WL and Virgin, HW and Gillanders, WE and Mosammaparast, N and Diamond, MS and Sibley, LD and Yokoyama, W and Schreiber, RD and Murphy, TL and Murphy, KM}, title = {WDFY4 is required for cross-presentation in response to viral and tumor antigens.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {694-699}, doi = {10.1126/science.aat5030}, pmid = {30409884}, issn = {1095-9203}, support = {U19 AI109948/AI/NIAID NIH HHS/United States ; F30 DK108498/DK/NIDDK NIH HHS/United States ; T32 CA009621/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 CA193318/CA/NCI NIH HHS/United States ; T32 AI007163/AI/NIAID NIH HHS/United States ; R01 CA190700/CA/NCI NIH HHS/United States ; U19 AI109725/AI/NIAID NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; }, abstract = {During the process of cross-presentation, viral or tumor-derived antigens are presented to CD8+ T cells by Batf3-dependent CD8α+/XCR1+ classical dendritic cells (cDC1s). We designed a functional CRISPR screen for previously unknown regulators of cross-presentation, and identified the BEACH domain-containing protein WDFY4 as essential for cross-presentation of cell-associated antigens by cDC1s in mice. However, WDFY4 was not required for major histocompatibility complex class II presentation, nor for cross-presentation by monocyte-derived dendritic cells. In contrast to Batf3-/- mice, Wdfy4-/- mice displayed normal lymphoid and nonlymphoid cDC1 populations that produce interleukin-12 and protect against Toxoplasma gondii infection. However, similar to Batf3-/- mice, Wdfy4-/- mice failed to prime virus-specific CD8+ T cells in vivo or induce tumor rejection, revealing a critical role for cross-presentation in antiviral and antitumor immunity.}, } @article {pmid30409883, year = {2018}, author = {El Meouche, I and Dunlop, MJ}, title = {Heterogeneity in efflux pump expression predisposes antibiotic-resistant cells to mutation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {686-690}, doi = {10.1126/science.aar7981}, pmid = {30409883}, issn = {1095-9203}, support = {R01 AI102922/AI/NIAID NIH HHS/United States ; R21 AI137843/AI/NIAID NIH HHS/United States ; }, abstract = {Antibiotic resistance is often the result of mutations that block drug activity; however, bacteria also evade antibiotics by transiently expressing genes such as multidrug efflux pumps. A crucial question is whether transient resistance can promote permanent genetic changes. Previous studies have established that antibiotic treatment can select tolerant cells that then mutate to achieve permanent resistance. Whether these mutations result from antibiotic stress or preexist within the population is unclear. To address this question, we focused on the multidrug pump AcrAB-TolC. Using time-lapse microscopy, we found that cells with higher acrAB expression have lower expression of the DNA mismatch repair gene mutS, lower growth rates, and higher mutation frequencies. Thus, transient antibiotic resistance from elevated acrAB expression can promote spontaneous mutations within single cells.}, } @article {pmid30409882, year = {2018}, author = {Crall, JD and Switzer, CM and Oppenheimer, RL and Ford Versypt, AN and Dey, B and Brown, A and Eyster, M and Guérin, C and Pierce, NE and Combes, SA and de Bivort, BL}, title = {Neonicotinoid exposure disrupts bumblebee nest behavior, social networks, and thermoregulation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {683-686}, doi = {10.1126/science.aat1598}, pmid = {30409882}, issn = {1095-9203}, abstract = {Neonicotinoid pesticides can negatively affect bee colonies, but the behavioral mechanisms by which these compounds impair colony growth remain unclear. Here, we investigate imidacloprid's effects on bumblebee worker behavior within the nest, using an automated, robotic platform for continuous, multicolony monitoring of uniquely identified workers. We find that exposure to field-realistic levels of imidacloprid impairs nursing and alters social and spatial dynamics within nests, but that these effects vary substantially with time of day. In the field, imidacloprid impairs colony thermoregulation, including the construction of an insulating wax canopy. Our results show that neonicotinoids induce widespread disruption of within-nest worker behavior that may contribute to impaired growth, highlighting the potential of automated techniques for characterizing the multifaceted, dynamic impacts of stressors on behavior in bee colonies.}, } @article {pmid30409881, year = {2018}, author = {Kubelka, V and Šálek, M and Tomkovich, P and Végvári, Z and Freckleton, RP and Székely, T}, title = {Global pattern of nest predation is disrupted by climate change in shorebirds.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {680-683}, doi = {10.1126/science.aat8695}, pmid = {30409881}, issn = {1095-9203}, abstract = {Ongoing climate change is thought to disrupt trophic relationships, with consequences for complex interspecific interactions, yet the effects of climate change on species interactions are poorly understood, and such effects have not been documented at a global scale. Using a single database of 38,191 nests from 237 populations, we found that shorebirds have experienced a worldwide increase in nest predation over the past 70 years. Historically, there existed a latitudinal gradient in nest predation, with the highest rates in the tropics; however, this pattern has been recently reversed in the Northern Hemisphere, most notably in the Arctic. This increased nest predation is consistent with climate-induced shifts in predator-prey relationships.}, } @article {pmid30409880, year = {2018}, author = {Drieu, C and Todorova, R and Zugaro, M}, title = {Nested sequences of hippocampal assemblies during behavior support subsequent sleep replay.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {675-679}, doi = {10.1126/science.aat2952}, pmid = {30409880}, issn = {1095-9203}, abstract = {Consolidation of spatial and episodic memories is thought to rely on replay of neuronal activity sequences during sleep. However, the network dynamics underlying the initial storage of memories during wakefulness have never been tested. Although slow, behavioral time scale sequences have been claimed to sustain sequential memory formation, fast ("theta") time scale sequences, nested within slow sequences, could be instrumental. We found that in rats traveling passively on a model train, place cells formed behavioral time scale sequences but theta sequences were degraded, resulting in impaired subsequent sleep replay. In contrast, when the rats actively ran on a treadmill while being transported on the train, place cells generated clear theta sequences and accurate trajectory replay during sleep. Our results support the view that nested sequences underlie the initial formation of memory traces subsequently consolidated during sleep.}, } @article {pmid30409879, year = {2018}, author = {Hopkins, BJ and Shao-Horn, Y and Hart, DP}, title = {Suppressing corrosion in primary aluminum-air batteries via oil displacement.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {658-661}, doi = {10.1126/science.aat9149}, pmid = {30409879}, issn = {1095-9203}, abstract = {Primary aluminum-air batteries boast high theoretical energy densities, but negative electrode corrosion irreversibly limits their shelf life. Most corrosion mitigation methods are insufficient or compromise power and energy density. We suppressed open-circuit corrosion by displacing electrolyte from the electrode surface with a nonconducting oil during battery standby. High power and energy density are enabled by displacing the oil with electrolyte for battery discharge. The underwater-oleophobic wetting properties of the designed cell surfaces allow for reversible oil displacement. We demonstrate this method in an aluminum-air cell that achieves a 420% increase in usable energy density and 99.99% reduction in corrosion, which lowers self-discharge to a rate of 0.02% a month and enables system energy densities of 700 watt-hours per liter and 900 watt-hours per kilogram.}, } @article {pmid30409878, year = {2018}, author = {Huang, H and Chang, F and Schwebel, DC and Ning, P and Cheng, P and Hu, G}, title = {Improve traffic death statistics in China.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {650}, doi = {10.1126/science.aav5117}, pmid = {30409878}, issn = {1095-9203}, } @article {pmid30409877, year = {2018}, author = {Carr, R and Coleman, J and Gratta, G and Heeger, K and Huber, P and Hor, Y and Kawasaki, T and Kim, SB and Kim, Y and Learned, J and Lindner, M and Nakajima, K and Seo, SH and Suekane, F and Vacheret, A and Wang, W and Zhan, L}, title = {Neutrino physics for Korean diplomacy.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {649-650}, doi = {10.1126/science.aav8136}, pmid = {30409877}, issn = {1095-9203}, } @article {pmid30409876, year = {2018}, author = {Langenegger, TW}, title = {Denuclearizing North Korea requires trust.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {649}, doi = {10.1126/science.aav4636}, pmid = {30409876}, issn = {1095-9203}, } @article {pmid30409875, year = {2018}, author = {Lodahl, P}, title = {Scaling up solid-state quantum photonics.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {646}, doi = {10.1126/science.aav3076}, pmid = {30409875}, issn = {1095-9203}, mesh = {*Diamond ; *Optics and Photonics ; Photons ; Quantum Theory ; }, } @article {pmid30409874, year = {2018}, author = {Scott, WG and Nagai, K}, title = {Recruiting more proteins to the RNA world.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {644-645}, doi = {10.1126/science.aav4743}, pmid = {30409874}, issn = {1095-9203}, mesh = {Proteins ; *RNA ; RNA, Transfer ; *Ribonuclease P ; Saccharomyces cerevisiae ; }, } @article {pmid30409873, year = {2018}, author = {Raine, NE}, title = {Pesticide affects social behavior of bees.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {643-644}, doi = {10.1126/science.aav5273}, pmid = {30409873}, issn = {1095-9203}, mesh = {Animals ; Bees ; Body Temperature Regulation ; *Neonicotinoids ; *Pesticides ; Social Behavior ; }, } @article {pmid30409872, year = {2018}, author = {Barbet, G and Blander, JM}, title = {A key ingredient for priming killer T cells.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {641-642}, doi = {10.1126/science.aav3683}, pmid = {30409872}, issn = {1095-9203}, mesh = {*Antigens, Neoplasm ; CD8-Positive T-Lymphocytes/immunology ; *Cross-Priming ; Cytotoxicity, Immunologic ; Dendritic Cells/immunology ; Killer Cells, Natural/immunology ; Lymphocyte Activation ; T-Lymphocytes, Cytotoxic/immunology ; }, } @article {pmid30409871, year = {2018}, author = {Levi-Schaffer, F and Scheffel, J}, title = {Dangerous liaisons in anaphylaxis.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {640-641}, doi = {10.1126/science.aav4505}, pmid = {30409871}, issn = {1095-9203}, } @article {pmid30409870, year = {2018}, author = {Wagner, W and Fisher, E and Pascual, P}, title = {Whose science? A new era in regulatory "science wars".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {636-639}, doi = {10.1126/science.aau3205}, pmid = {30409870}, issn = {1095-9203}, } @article {pmid30409869, year = {2018}, author = {Law, YH}, title = {Stopping the sting.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {631-635}, doi = {10.1126/science.362.6415.631}, pmid = {30409869}, issn = {1095-9203}, } @article {pmid30409868, year = {2018}, author = {Grimm, D}, title = {U.S. labs using a record number of monkeys.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {630}, doi = {10.1126/science.362.6415.630}, pmid = {30409868}, issn = {1095-9203}, } @article {pmid30409867, year = {2018}, author = {Rochmyaningsih, D}, title = {Indonesian fatwa causes immunization rates to drop.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {628-629}, doi = {10.1126/science.362.6415.628}, pmid = {30409867}, issn = {1095-9203}, } @article {pmid30409866, year = {2018}, author = {Wade, L}, title = {Ancient DNA tracks migrations around Americas.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {627-628}, doi = {10.1126/science.362.6415.627}, pmid = {30409866}, issn = {1095-9203}, } @article {pmid30409865, year = {2018}, author = {Curry, A}, title = {Early Mongolians ate dairy, but lacked the gene to digest it.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {626-627}, doi = {10.1126/science.362.6415.626}, pmid = {30409865}, issn = {1095-9203}, } @article {pmid30409864, year = {2018}, author = {Cho, A}, title = {World poised to adopt new metric units.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {625-626}, doi = {10.1126/science.362.6415.625}, pmid = {30409864}, issn = {1095-9203}, } @article {pmid30409863, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {622-624}, doi = {10.1126/science.362.6415.622}, pmid = {30409863}, issn = {1095-9203}, } @article {pmid30409862, year = {2018}, author = {Sahel, JA}, title = {Facing hatred.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {621}, doi = {10.1126/science.aav9391}, pmid = {30409862}, issn = {1095-9203}, } @article {pmid30409861, year = {2018}, author = {Bellmund, JLS and Gärdenfors, P and Moser, EI and Doeller, CF}, title = {Navigating cognition: Spatial codes for human thinking.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {}, doi = {10.1126/science.aat6766}, pmid = {30409861}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The hippocampal formation has long been suggested to underlie both memory formation and spatial navigation. We discuss how neural mechanisms identified in spatial navigation research operate across information domains to support a wide spectrum of cognitive functions. In our framework, place and grid cell population codes provide a representational format to map variable dimensions of cognitive spaces. This highly dynamic mapping system enables rapid reorganization of codes through remapping between orthogonal representations across behavioral contexts, yielding a multitude of stable cognitive spaces at different resolutions and hierarchical levels. Action sequences result in trajectories through cognitive space, which can be simulated via sequential coding in the hippocampus. In this way, the spatial representational format of the hippocampal formation has the capacity to support flexible cognition and behavior.}, } @article {pmid30409860, year = {2018}, author = {Blount, ZD and Lenski, RE and Losos, JB}, title = {Contingency and determinism in evolution: Replaying life's tape.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {}, doi = {10.1126/science.aam5979}, pmid = {30409860}, issn = {1095-9203}, abstract = {Historical processes display some degree of "contingency," meaning their outcomes are sensitive to seemingly inconsequential events that can fundamentally change the future. Contingency is what makes historical outcomes unpredictable. Unlike many other natural phenomena, evolution is a historical process. Evolutionary change is often driven by the deterministic force of natural selection, but natural selection works upon variation that arises unpredictably through time by random mutation, and even beneficial mutations can be lost by chance through genetic drift. Moreover, evolution has taken place within a planetary environment with a particular history of its own. This tension between determinism and contingency makes evolutionary biology a kind of hybrid between science and history. While philosophers of science examine the nuances of contingency, biologists have performed many empirical studies of evolutionary repeatability and contingency. Here, we review the experimental and comparative evidence from these studies. Replicate populations in evolutionary "replay" experiments often show parallel changes, especially in overall performance, although idiosyncratic outcomes show that the particulars of a lineage's history can affect which of several evolutionary paths is taken. Comparative biologists have found many notable examples of convergent adaptation to similar conditions, but quantification of how frequently such convergence occurs is difficult. On balance, the evidence indicates that evolution tends to be surprisingly repeatable among closely related lineages, but disparate outcomes become more likely as the footprint of history grows deeper. Ongoing research on the structure of adaptive landscapes is providing additional insight into the interplay of fate and chance in the evolutionary process.}, } @article {pmid30409859, year = {2018}, author = {Choi, HW and Suwanpradid, J and Kim, IH and Staats, HF and Haniffa, M and MacLeod, AS and Abraham, SN}, title = {Perivascular dendritic cells elicit anaphylaxis by relaying allergens to mast cells via microvesicles.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {}, doi = {10.1126/science.aao0666}, pmid = {30409859}, issn = {1095-9203}, support = {R01 AI096305/AI/NIAID NIH HHS/United States ; R21 AI128727/AI/NIAID NIH HHS/United States ; R56 DK095198/DK/NIDDK NIH HHS/United States ; U01 AI082107/AI/NIAID NIH HHS/United States ; }, abstract = {Anaphylactic reactions are triggered when allergens enter the blood circulation and activate immunoglobulin E (IgE)-sensitized mast cells (MCs), causing systemic discharge of prestored proinflammatory mediators. As MCs are extravascular, how they perceive circulating allergens remains a conundrum. Here, we describe the existence of a CD301b+ perivascular dendritic cell (DC) subset that continuously samples blood and relays antigens to neighboring MCs, which vigorously degranulate and trigger anaphylaxis. DC antigen transfer involves the active discharge of surface-associated antigens on 0.5- to 1.0-micrometer microvesicles (MVs) generated by vacuolar protein sorting 4 (VPS4). Antigen sharing by DCs is not limited to MCs, as neighboring DCs also acquire antigen-bearing MVs. This capacity of DCs to distribute antigen-bearing MVs to various immune cells in the perivascular space potentiates inflammatory and immune responses to blood-borne antigens.}, } @article {pmid30409809, year = {2018}, author = {Chong, L and Wen, J and Kubal, J and Sen, FG and Zou, J and Greeley, J and Chan, M and Barkholtz, H and Ding, W and Liu, DJ}, title = {Ultralow-loading platinum-cobalt fuel cell catalysts derived from imidazolate frameworks.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6420}, pages = {1276-1281}, doi = {10.1126/science.aau0630}, pmid = {30409809}, issn = {1095-9203}, abstract = {Achieving high catalytic performance with the lowest possible amount of platinum is critical for fuel cell cost reduction. Here we describe a method of preparing highly active yet stable electrocatalysts containing ultralow-loading platinum content by using cobalt or bimetallic cobalt and zinc zeolitic imidazolate frameworks as precursors. Synergistic catalysis between strained platinum-cobalt core-shell nanoparticles over a platinum-group metal (PGM)-free catalytic substrate led to excellent fuel cell performance under 1 atmosphere of O2 or air at both high-voltage and high-current domains. Two catalysts achieved oxygen reduction reaction (ORR) mass activities of 1.08 amperes per milligram of platinum (A mgPt-1) and 1.77 A mgPt-1 and retained 64% and 15% of initial values after 30,000 voltage cycles in a fuel cell. Computational modeling reveals that the interaction between platinum-cobalt nanoparticles and PGM-free sites improves ORR activity and durability.}, } @article {pmid30409808, year = {2018}, author = {Kim, JM and Seok, OH and Ju, S and Heo, JE and Yeom, J and Kim, DS and Yoo, JY and Varshavsky, A and Lee, C and Hwang, CS}, title = {Formyl-methionine as an N-degron of a eukaryotic N-end rule pathway.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {}, doi = {10.1126/science.aat0174}, pmid = {30409808}, issn = {1095-9203}, support = {R01 GM031530/GM/NIGMS NIH HHS/United States ; R01 DK039520/DK/NIDDK NIH HHS/United States ; }, abstract = {In bacteria, nascent proteins bear the pretranslationally generated N-terminal (Nt) formyl-methionine (fMet) residue. Nt-fMet of bacterial proteins is a degradation signal, termed fMet/N-degron. By contrast, proteins synthesized by cytosolic ribosomes of eukaryotes were presumed to bear unformylated Nt-Met. Here we found that the yeast formyltransferase Fmt1, although imported into mitochondria, could also produce Nt-formylated proteins in the cytosol. Nt-formylated proteins were strongly up-regulated in stationary phase or upon starvation for specific amino acids. This up-regulation strictly required the Gcn2 kinase, which phosphorylates Fmt1 and mediates its retention in the cytosol. We also found that the Nt-fMet residues of Nt-formylated proteins act as fMet/N-degrons and identified the Psh1 ubiquitin ligase as the recognition component of the eukaryotic fMet/N-end rule pathway, which destroys Nt-formylated proteins.}, } @article {pmid30409807, year = {2018}, author = {Moreno-Mayar, JV and Vinner, L and de Barros Damgaard, P and de la Fuente, C and Chan, J and Spence, JP and Allentoft, ME and Vimala, T and Racimo, F and Pinotti, T and Rasmussen, S and Margaryan, A and Iraeta Orbegozo, M and Mylopotamitaki, D and Wooller, M and Bataille, C and Becerra-Valdivia, L and Chivall, D and Comeskey, D and Devièse, T and Grayson, DK and George, L and Harry, H and Alexandersen, V and Primeau, C and Erlandson, J and Rodrigues-Carvalho, C and Reis, S and Bastos, MQR and Cybulski, J and Vullo, C and Morello, F and Vilar, M and Wells, S and Gregersen, K and Hansen, KL and Lynnerup, N and Mirazón Lahr, M and Kjær, K and Strauss, A and Alfonso-Durruty, M and Salas, A and Schroeder, H and Higham, T and Malhi, RS and Rasic, JT and Souza, L and Santos, FR and Malaspinas, AS and Sikora, M and Nielsen, R and Song, YS and Meltzer, DJ and Willerslev, E}, title = {Early human dispersals within the Americas.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {}, doi = {10.1126/science.aav2621}, pmid = {30409807}, issn = {1095-9203}, support = {R01 GM094402/GM/NIGMS NIH HHS/United States ; //European Research Council/International ; }, abstract = {Studies of the peopling of the Americas have focused on the timing and number of initial migrations. Less attention has been paid to the subsequent spread of people within the Americas. We sequenced 15 ancient human genomes spanning from Alaska to Patagonia; six are ≥10,000 years old (up to ~18× coverage). All are most closely related to Native Americans, including those from an Ancient Beringian individual and two morphologically distinct "Paleoamericans." We found evidence of rapid dispersal and early diversification that included previously unknown groups as people moved south. This resulted in multiple independent, geographically uneven migrations, including one that provides clues of a Late Pleistocene Australasian genetic signal, as well as a later Mesoamerican-related expansion. These led to complex and dynamic population histories from North to South America.}, } @article {pmid30409806, year = {2018}, author = {Martin, HC and Jones, WD and McIntyre, R and Sanchez-Andrade, G and Sanderson, M and Stephenson, JD and Jones, CP and Handsaker, J and Gallone, G and Bruntraeger, M and McRae, JF and Prigmore, E and Short, P and Niemi, M and Kaplanis, J and Radford, EJ and Akawi, N and Balasubramanian, M and Dean, J and Horton, R and Hulbert, A and Johnson, DS and Johnson, K and Kumar, D and Lynch, SA and Mehta, SG and Morton, J and Parker, MJ and Splitt, M and Turnpenny, PD and Vasudevan, PC and Wright, M and Bassett, A and Gerety, SS and Wright, CF and FitzPatrick, DR and Firth, HV and Hurles, ME and Barrett, JC and , }, title = {Quantifying the contribution of recessive coding variation to developmental disorders.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1161-1164}, doi = {10.1126/science.aar6731}, pmid = {30409806}, issn = {1095-9203}, abstract = {We estimated the genome-wide contribution of recessive coding variation in 6040 families from the Deciphering Developmental Disorders study. The proportion of cases attributable to recessive coding variants was 3.6% in patients of European ancestry, compared with 50% explained by de novo coding mutations. It was higher (31%) in patients with Pakistani ancestry, owing to elevated autozygosity. Half of this recessive burden is attributable to known genes. We identified two genes not previously associated with recessive developmental disorders, KDM5B and EIF3F, and functionally validated them with mouse and cellular models. Our results suggest that recessive coding variants account for a small fraction of currently undiagnosed nonconsanguineous individuals, and that the role of noncoding variants, incomplete penetrance, and polygenic mechanisms need further exploration.}, } @article {pmid30409805, year = {2018}, author = {Guo, A and Wang, Y and Chen, B and Wang, Y and Yuan, J and Zhang, L and Hall, D and Wu, J and Shi, Y and Zhu, Q and Chen, C and Thiel, WH and Zhan, X and Weiss, RM and Zhan, F and Musselman, CA and Pufall, M and Zhu, W and Au, KF and Hong, J and Anderson, ME and Grueter, CE and Song, LS}, title = {E-C coupling structural protein junctophilin-2 encodes a stress-adaptive transcription regulator.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {}, doi = {10.1126/science.aan3303}, pmid = {30409805}, issn = {1095-9203}, support = {P30 DK054759/DK/NIDDK NIH HHS/United States ; R01 HL090905/HL/NHLBI NIH HHS/United States ; R01 HL125436/HL/NHLBI NIH HHS/United States ; R01 HL130346/HL/NHLBI NIH HHS/United States ; }, abstract = {Junctophilin-2 (JP2) is a structural protein required for normal excitation-contraction (E-C) coupling. After cardiac stress, JP2 is cleaved by the calcium ion-dependent protease calpain, which disrupts the E-C coupling ultrastructural machinery and drives heart failure progression. We found that stress-induced proteolysis of JP2 liberates an N-terminal fragment (JP2NT) that translocates to the nucleus, binds to genomic DNA, and controls expression of a spectrum of genes in cardiomyocytes. Transgenic overexpression of JP2NT in mice modifies the transcriptional profile, resulting in attenuated pathological remodeling in response to cardiac stress. Conversely, loss of nuclear JP2NT function accelerates stress-induced development of hypertrophy and heart failure in mutant mice. These data reveal a self-protective mechanism in failing cardiomyocytes that transduce mechanical information (E-C uncoupling) into salutary transcriptional reprogramming in the stressed heart.}, } @article {pmid30409804, year = {2018}, author = {Fraiberger, SP and Sinatra, R and Resch, M and Riedl, C and Barabási, AL}, title = {Quantifying reputation and success in art.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {825-829}, doi = {10.1126/science.aau7224}, pmid = {30409804}, issn = {1095-9203}, abstract = {In areas of human activity where performance is difficult to quantify in an objective fashion, reputation and networks of influence play a key role in determining access to resources and rewards. To understand the role of these factors, we reconstructed the exhibition history of half a million artists, mapping out the coexhibition network that captures the movement of art between institutions. Centrality within this network captured institutional prestige, allowing us to explore the career trajectory of individual artists in terms of access to coveted institutions. Early access to prestigious central institutions offered life-long access to high-prestige venues and reduced dropout rate. By contrast, starting at the network periphery resulted in a high dropout rate, limiting access to central institutions. A Markov model predicts the career trajectory of individual artists and documents the strong path and history dependence of valuation in art.}, } @article {pmid30409803, year = {2018}, author = {Guinn, EJ and Tian, P and Shin, M and Best, RB and Marqusee, S}, title = {A small single-domain protein folds through the same pathway on and off the ribosome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12206-12211}, pmid = {30409803}, issn = {1091-6490}, support = {F32 GM110940/GM/NIGMS NIH HHS/United States ; R01 GM050945/GM/NIGMS NIH HHS/United States ; }, abstract = {In vivo, proteins fold and function in a complex environment subject to many stresses that can modulate a protein's energy landscape. One aspect of the environment pertinent to protein folding is the ribosome, since proteins have the opportunity to fold while still bound to the ribosome during translation. We use a combination of force and chemical denaturant (chemomechanical unfolding), as well as point mutations, to characterize the folding mechanism of the src SH3 domain both as a stalled ribosome nascent chain and free in solution. Our results indicate that src SH3 folds through the same pathway on and off the ribosome. Molecular simulations also indicate that the ribosome does not affect the folding pathway for this small protein. Taken together, we conclude that the ribosome does not alter the folding mechanism of this small protein. These results, if general, suggest the ribosome may exert a bigger influence on the folding of multidomain proteins or protein domains that can partially fold before the entire domain sequence is outside the ribosome exit tunnel.}, } @article {pmid30409802, year = {2018}, author = {Ungerer, J and Wendt, KE and Hendry, JI and Maranas, CD and Pakrasi, HB}, title = {Comparative genomics reveals the molecular determinants of rapid growth of the cyanobacterium Synechococcus elongatus UTEX 2973.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {50}, pages = {E11761-E11770}, doi = {10.1073/pnas.1814912115}, pmid = {30409802}, issn = {1091-6490}, abstract = {Cyanobacteria are emerging as attractive organisms for sustainable bioproduction. We previously described Synechococcus elongatus UTEX 2973 as the fastest growing cyanobacterium known. Synechococcus 2973 exhibits high light tolerance and an increased photosynthetic rate and produces biomass at three times the rate of its close relative, the model strain Synechococcus elongatus 7942. The two strains differ at 55 genetic loci, and some of these loci must contain the genetic determinants of rapid photoautotrophic growth and improved photosynthetic rate. Using CRISPR/Cpf1, we performed a comprehensive mutational analysis of Synechococcus 2973 and identified three specific genes, atpA, ppnK, and rpaA, with SNPs that confer rapid growth. The fast-growth-associated allele of each gene was then used to replace the wild-type alleles in Synechococcus 7942. Upon incorporation, each allele successively increased the growth rate of Synechococcus 7942; remarkably, inclusion of all three alleles drastically reduced the doubling time from 6.8 to 2.3 hours. Further analysis revealed that our engineering effort doubled the photosynthetic productivity of Synechococcus 7942. We also determined that the fast-growth-associated allele of atpA yielded an ATP synthase with higher specific activity, while that of ppnK encoded a NAD+ kinase with significantly improved kinetics. The rpaA SNPs cause broad changes in the transcriptional profile, as this gene is the master output regulator of the circadian clock. This pioneering study has revealed the molecular basis for rapid growth, demonstrating that limited genetic changes can dramatically improve the growth rate of a microbe by as much as threefold.}, } @article {pmid30409801, year = {2018}, author = {Martins, BMC and Tooke, AK and Thomas, P and Locke, JCW}, title = {Cell size control driven by the circadian clock and environment in cyanobacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11415-E11424}, pmid = {30409801}, issn = {1091-6490}, support = {BB/L014130/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {How cells maintain their size has been extensively studied under constant conditions. In the wild, however, cells rarely experience constant environments. Here, we examine how the 24-h circadian clock and environmental cycles modulate cell size control and division timings in the cyanobacterium Synechococcus elongatus using single-cell time-lapse microscopy. Under constant light, wild-type cells follow an apparent sizer-like principle. Closer inspection reveals that the clock generates two subpopulations, with cells born in the subjective day following different division rules from cells born in subjective night. A stochastic model explains how this behavior emerges from the interaction of cell size control with the clock. We demonstrate that the clock continuously modulates the probability of cell division throughout day and night, rather than solely applying an on-off gate to division, as previously proposed. Iterating between modeling and experiments, we go on to identify an effective coupling of the division rate to time of day through the combined effects of the environment and the clock on cell division. Under naturally graded light-dark cycles, this coupling narrows the time window of cell divisions and shifts divisions away from when light levels are low and cell growth is reduced. Our analysis allows us to disentangle, and predict the effects of, the complex interactions between the environment, clock, and cell size control.}, } @article {pmid30409800, year = {2018}, author = {Breier, RE and Lalescu, CC and Waas, D and Wilczek, M and Mazza, MG}, title = {Emergence of phytoplankton patchiness at small scales in mild turbulence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12112-12117}, pmid = {30409800}, issn = {1091-6490}, abstract = {Phytoplankton often encounter turbulence in their habitat. As most toxic phytoplankton species are motile, resolving the interplay of motility and turbulence has fundamental repercussions on our understanding of their own ecology and of the entire ecosystems they inhabit. The spatial distribution of motile phytoplankton cells exhibits patchiness at distances of decimeter to millimeter scales for numerous species with different motility strategies. The explanation of this general phenomenon remains challenging. Furthermore, hydrodynamic cell-cell interactions, which grow more relevant as the density in the patches increases, have been so far ignored. Here, we combine particle simulations and continuum theory to study the emergence of patchiness in motile microorganisms in three dimensions. By addressing the combined effects of motility, cell-cell interaction, and turbulent flow conditions, we uncover a general mechanism: The coupling of cell-cell interactions to the turbulent dynamics favors the formation of dense patches. Identification of the important length and time scales, independent from the motility mode, allows us to elucidate a general physical mechanism underpinning the emergence of patchiness. Our results shed light on the dynamical characteristics necessary for the formation of patchiness and complement current efforts to unravel planktonic ecological interactions.}, } @article {pmid30409229, year = {2018}, author = {Fernández Bustillo, JM and Fernández Pombo, A and Gómez Bahamonde, R and Sanmartín López, E and Gualillo, O}, title = {Vitamin D levels in a pediatric population of a primary care centre: a public health problem?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {801}, pmid = {30409229}, issn = {1756-0500}, abstract = {OBJECTIVE: Vitamin D deficiency is a public health problem that occurs more frequently than expected. The aim of this study is to evaluate the vitamin D levels of children attending the paediatrics unit of the Bertamiráns primary care centre (A Coruña NW Spain). This is an observational study carried out during 1 year on a random sample of the pediatric population aged between 5 and 15 years. The levels of vitamin D (25(OH)D) were determined by immunoassay (ADVIA Centaur Vitamin D®). The results were classified as sufficient (> 20 ng/ml), insufficient (10-20 ng/ml) and deficient (< 10 ng/ml).

RESULTS: 153 analyses of vitamin D were carried out (58.2% in girls and 41.8% in boys), distributed in two age groups: 5-10 (62) and 10-15 (91). 66% of the total of the sample presented some degree of vitamin D deficit (60.1% insufficient (92) and 5.9% (11) deficient). In Galicia, there is a high prevalence of vitamin D deficiency/insufficiency in the healthy population, which increases if the patients present some kind of chronic pathology, thus leading to a public health problem. It is advisable to increase the consumption of fortified foods and/or to reconsider the administration of vitamin supplements.}, } @article {pmid30409220, year = {2018}, author = {Poirier, S and Rué, O and Coeuret, G and Champomier-Vergès, MC and Loux, V and Chaillou, S}, title = {Detection of an amplification bias associated to Leuconostocaceae family with a universal primer routinely used for monitoring microbial community structures within food products.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {802}, pmid = {30409220}, issn = {1756-0500}, support = {ANR-16-CE21-0006//ANR/ ; }, abstract = {OBJECTIVES: Sequencing of 16S rDNA V3-V4 region is widely applied for food community profiling. However, two different universal forward primers (named here MUYZER-primer1 and KLINDWORTH-primer2) targeting an identical conservative sequence upstream of the V3 region of 16S rRNA gene, and only distinguished by a single mismatch are both used. This study was carried out to compare whether the accuracy of food microbiota analysis would depend on the choice of one of these two primers.

RESULTS: Alignment of both primers with common food-borne bacteria 16S sequences revealed that the mismatch between both primers might specifically affect the amplification of Leuconostoc, Oenococcus and Fructobacillus species but not Weissella species. Food products containing either Leuconostoc and/or Weissella were selected for a detection test. As expected from our in silico analysis, our study showed that this mismatch induced a strong biased amplification specifically associated to the OTUs belonging to the genus Leuconostoc but not to the genus Weissella. In presence of Muyzer-primer1, none of the sequences expected for Leuconostoc genus was detected whereas those sequences were correctly amplified with Klindworth-primer2. Since Leuconostoc is an important genus in food, agro-environments and in digestive tract of animals, we recommend that Muyzer-primer1 should thus be abandoned for the bacterial characterization of their associated microbiota.}, } @article {pmid30409208, year = {2018}, author = {Tadesse, S and Kahsay, T and Adhanom, G and Kahsu, G and Legese, H and G/Wahid, A and Derbie, A}, title = {Correction to: Prevalence, antimicrobial susceptibility profile and predictors of asymptomatic bacteriuria among pregnant women in Adigrat General Hospital, Northern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {798}, pmid = {30409208}, issn = {1756-0500}, abstract = {Following publication of the original article [1], the authors reported that one of the authors' names was spelled incorrectly. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.}, } @article {pmid30409206, year = {2018}, author = {Taye, S and Getachew, M and Desalegn, Z and Biratu, A and Mubashir, K}, title = {Bacterial profile, antibiotic susceptibility pattern and associated factors among pregnant women with Urinary Tract Infection in Goba and Sinana Woredas, Bale Zone, Southeast Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {799}, pmid = {30409206}, issn = {1756-0500}, abstract = {OBJECTIVE: Urinary tract infection (UTI) is one of the commonest infections affecting millions worldwide, especially pregnant women. It can lead to poor maternal and perinatal outcomes. Untreated UTI can be associated with serious obstetric complications. So the objective of present study was to determine the bacterial profile, antibiotic susceptibility pattern and associated factors of UTI among pregnant women in Goba and Sinana Woredas, Bale Zone, Southeast Ethiopia.

RESULTS: The overall prevalence of UTI was 44/169 (26%) with 18/51 (35.3%) in symptomatic and 26/118 (22%) in asymptomatic pregnant women, respectively. Of the 44 bacterial isolates, E. coli 12/44 (27.3%), K. pneumonia 9/44 (20.5%) and S. marcescens 4/44 (9.1%) were the commonest bacterial pathogens. C. freundii 3/44 (6.8%), M. morganii 3/44 (6.8%), P. aeruginosa 3/44 (6.8%) and S. enteritidis 3/44 (6.8%) isolates were the moderately identified bacterial species. K. oxytoca 1/44 (2.3%) was the least common bacterium to be detected. The antibiotic susceptibility pattern showed that 90.9%, 88.6% and 86.3% of the isolates were sensitive to amoxicillin/clavulanic acid, gentamycin and norfloxacin, respectively. Significant bacteriuria was associated with low educational status (p = 0.024; AOR = 6.617; CI = 1.87-9.94) and kidney problems (p = 0.018; AOR = 0.286; CI = 1.19-2.81).}, } @article {pmid30409183, year = {2018}, author = {Peltier, E and Sharma, V and Martí Raga, M and Roncoroni, M and Bernard, M and Jiranek, V and Gibon, Y and Marullo, P}, title = {Dissection of the molecular bases of genotype x environment interactions: a study of phenotypic plasticity of Saccharomyces cerevisiae in grape juices.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {772}, pmid = {30409183}, issn = {1471-2164}, support = {NA//Conseil Régional Aquitaine/ ; }, abstract = {BACKGROUND: The ability of a genotype to produce different phenotypes according to its surrounding environment is known as phenotypic plasticity. Within different individuals of the same species, phenotypic plasticity can vary greatly. This contrasting response is caused by gene-by-environment interactions (GxE). Understanding GxE interactions is particularly important in agronomy, since selected breeds and varieties may have divergent phenotypes according to their growing environment. Industrial microbes such as Saccharomyces cerevisiae are also faced with a large range of fermentation conditions that affect their technological properties. Finding the molecular determinism of such variations is a critical task for better understanding the genetic bases of phenotypic plasticity and can also be helpful in order to improve breeding methods.

RESULTS: In this study we implemented a QTL mapping program using two independent cross (~ 100 progeny) in order to investigate the molecular basis of yeast phenotypic response in a wine fermentation context. Thanks to whole genome sequencing approaches, both crosses were genotyped, providing saturated genetic maps of thousands of markers. Linkage analyses allowed the detection of 78 QTLs including 21 with significant interaction with the environmental conditions. Molecular dissection of a major QTL demonstrated that the sulfite pump Ssu1p has a pleiotropic effect and impacts the phenotypic plasticity of several traits.

CONCLUSIONS: The detection of QTLs and their interactions with environment emphasizes the complexity of yeast industrial traits. The validation of the interaction of SSU1 allelic variants with the nature of the fermented juice increases knowledge about the impact of the sulfite pump during fermentation. All together these results pave the way for exploiting and deciphering the genetic determinism of phenotypic plasticity.}, } @article {pmid30409177, year = {2018}, author = {Zhu, Q and Dupont, CL and Jones, MB and Pham, KM and Jiang, ZD and DuPont, HL and Highlander, SK}, title = {Visualization-assisted binning of metagenome assemblies reveals potential new pathogenic profiles in idiopathic travelers' diarrhea.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {201}, pmid = {30409177}, issn = {2049-2618}, support = {R21 DK099573/DK/NIDDK NIH HHS/United States ; R21DK099573//National Institute of Diabetes and Digestive and Kidney Diseases/ ; }, abstract = {BACKGROUND: Travelers' diarrhea (TD) is often caused by enterotoxigenic Escherichia coli, enteroaggregative E. coli, other bacterial pathogens, Norovirus, and occasionally parasites. Nevertheless, standard diagnostic methods fail to identify pathogens in more than 40% of TD patients. It is predicted that new pathogens may be causative agents of the disease.

RESULTS: We performed a comprehensive amplicon and whole genome shotgun (WGS) metagenomic study of the fecal microbiomes from 23 TD patients and seven healthy travelers, all of which were negative for the known etiologic agents of TD based on standard microbiological and immunological assays. Abnormal and diverse taxonomic profiles in TD samples were revealed. WGS reads were assembled and the resulting contigs were visualized using multiple query types. A semi-manual workflow was applied to isolate independent genomes from metagenomic pools. A total of 565 genome bins were extracted, 320 of which were complete enough to be characterized as cellular genomes; 160 were viral genomes. We made predictions of the etiology of disease for many of the individual subjects based on the properties and features of the recovered genomes. Multiple patients with low-diversity metagenomes were predominated by one to several E. coli strains. Functional annotation allowed prediction of pathogenic type in many cases. Five patients were co-infected with E. coli and other members of Enterobacteriaceae, including Enterobacter, Klebsiella, and Citrobacter; these may represent blooms of organisms that appear following secretory diarrhea. New "dark matter" microbes were observed in multiple samples. In one, we identified a novel TM7 genome that phylogenetically clustered with a sludge isolate; it carries genes encoding potential virulence factors. In multiple samples, we observed high proportions of putative novel viral genomes, some of which form clusters with the ubiquitous gut virus, crAssphage. The total relative abundance of viruses was significantly higher in healthy travelers versus TD patients.

CONCLUSION: Our study highlights the strength of assembly-based metagenomics, especially the manually curated, visualization-assisted binning of contigs, in resolving unusual and under-characterized pathogenic profiles of human-associated microbiomes. Results show that TD may be polymicrobial, with multiple novel cellular and viral strains as potential players in the diarrheal disease.}, } @article {pmid30409169, year = {2018}, author = {Ma, C and Sun, Z and Zeng, B and Huang, S and Zhao, J and Zhang, Y and Su, X and Xu, J and Wei, H and Zhang, H}, title = {Cow-to-mouse fecal transplantations suggest intestinal microbiome as one cause of mastitis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {200}, pmid = {30409169}, issn = {2049-2618}, support = {ID0E61AE8001//National Natural Science Foundation of China/ ; ID0EO2AE8002//Postdoctoral Science Foundation of Jiangsu Province/ ; }, abstract = {BACKGROUND: Mastitis, which affects nearly all lactating mammals including human, is generally thought to be caused by local infection of the mammary glands. For treatment, antibiotics are commonly prescribed, which however are of concern in both treatment efficacy and neonate safety. Here, using bovine mastitis which is the most costly disease in the dairy industry as a model, we showed that intestinal microbiota alone can lead to mastitis.

RESULTS: Fecal microbiota transplantation (FMT) from mastitis, but not healthy cows, to germ-free (GF) mice resulted in mastitis symptoms in mammary gland and inflammations in serum, spleen, and colon. Probiotic intake in parallel with FMT from diseased cows led to relieved mastitis symptoms in mice, by shifting the murine intestinal microbiota to a state that is functionally distinct from either healthy or diseased microbiota yet structurally similar to the latter. Despite conservation in mastitis symptoms, diseased cows and mice shared few mastitis-associated bacterial organismal or functional markers, suggesting striking divergence in mastitis-associated intestinal microbiota among lactating mammals. Moreover, an "amplification effect" of disease-health distinction in both microbiota structure and function was apparent during the cow-to-mouse FMT.

CONCLUSIONS: Hence, dysbiosis of intestinal microbiota may be one cause of mastitis, and probiotics that restore intestinal microbiota function are an effective and safe strategy to treat mastitis.}, } @article {pmid30409159, year = {2018}, author = {Watanabe, S and Aiba, Y and Tan, XE and Li, FY and Boonsiri, T and Thitiananpakorn, K and Cui, B and Sato'o, Y and Kiga, K and Sasahara, T and Cui, L}, title = {Complete genome sequencing of three human clinical isolates of Staphylococcus caprae reveals virulence factors similar to those of S. epidermidis and S. capitis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {810}, pmid = {30409159}, issn = {1471-2164}, support = {15H05654//Japan Society for the Promotion of Science (JSPS) KAKENHI/ ; 26460536//Japan Society for the Promotion of Science (JSPS) KAKENHI/ ; 17F17713//Japan Society for the Promotion of Science/ ; JP19fm0208028//Japan Agency for Medical Research and Development (AMED) J-PRIDE Grant/ ; }, abstract = {BACKGROUND: Staphylococcus caprae is an animal-associated bacterium regarded as part of goats' microflora. Recently, S. caprae has been reported to cause human nosocomial infections such as bacteremia and bone and joint infections. However, the mechanisms responsible for the development of nosocomial infections remain largely unknown. Moreover, the complete genome sequence of S. caprae has not been determined.

RESULTS: We determined the complete genome sequences of three methicillin-resistant S. caprae strains isolated from humans and compared these sequences with the genomes of S. epidermidis and S. capitis, both of which are closely related to S. caprae and are inhabitants of human skin capable of causing opportunistic infections. The genomes showed that S. caprae JMUB145, JMUB590, and JMUB898 strains contained circular chromosomes of 2,618,380, 2,629,173, and 2,598,513 bp, respectively. JMUB145 carried type V SCCmec, while JMUB590 and JMUB898 had type IVa SCCmec. A genome-wide phylogenetic SNP tree constructed using 83 complete genome sequences of 24 Staphylococcus species and 2 S. caprae draft genome sequences confirmed that S. caprae is most closely related to S. epidermidis and S. capitis. Comparative complete genome analysis of eight S. epidermidis, three S. capitis and three S. caprae strains revealed that they shared similar virulence factors represented by biofilm formation genes. These factors include wall teichoic acid synthesis genes, poly-gamma-DL-glutamic acid capsule synthesis genes, and other genes encoding nonproteinaceous adhesins. The 17 proteinases/adhesins and extracellular proteins known to be associated with biofilm formation in S. epidermidis were also conserved in these three species, and their biofilm formation could be detected in vitro. Moreover, two virulence-associated gene clusters, the type VII secretion system and capsular polysaccharide biosynthesis gene clusters, identified in S. aureus were present in S. caprae but not in S. epidermidis and S. capitis genomes.

CONCLUSION: The complete genome sequences of three methicillin-resistant S. caprae isolates from humans were determined for the first time. Comparative genome analysis revealed that S. caprae is closely related to S. epidermidis and S. capitis at the species level, especially in the ability to form biofilms, which may lead to increased virulence during the development of S. caprae infections.}, } @article {pmid30409158, year = {2018}, author = {Majalija, S and Luyombo, P and Tumwine, G}, title = {Sero-prevalence and associated risk factors of Brucellosis among Malaria negative febrile out-patients in Wakiso district, Central Uganda.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {803}, pmid = {30409158}, issn = {1756-0500}, support = {CGS 2/14/14//National Agricultural Research Organization/ ; }, abstract = {OBJECTIVE: Brucellosis is a zoonotic disease usually acquired through direct contact with the infected animals and consumption of contaminated milk and meat products. In humans Brucellosis presents similar signs with other febrile diseases like Malaria, typhoid and other febrile conditions. This study was carried out to determine the prevalence of Brucella abortus among patients with fever but were negative for Malaria.

RESULTS: A cross-sectional study was carried out in Namayumba Health Centre IV, Wakiso district involving 200 participants. Blood samples was screened for B. abortus using Serum Agglutination Test and confirmed with Tube Agglutination test. A questionnaire was used to collect data on socio-demographic characteristics and human Brucellosis related risk factors. Human B. abortus sero-prevalence was at 7.5% (n = 200). The prevalence was high among participants aged 18-35 years (13.3%), muslims 12 (14.0%), those with no formal education (33.3%) and divorced 2 (14.3%). Consuming of raw milk (OR 2.162, 95% CI 0.021-1.379) and being a Muslim (OR 6.101, 95% CI 1.601-23.248) were associated with increased risk of Brucella abortus. It was concluded that human Brucella infection due to Brucella abortus is commonly associated with consumers of raw milk products and muslims in Wakiso district.}, } @article {pmid30409155, year = {2018}, author = {Ernlund, AW and Schneider, RJ and Ruggles, KV}, title = {RIVET: comprehensive graphic user interface for analysis and exploration of genome-wide translatomics data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {809}, pmid = {30409155}, issn = {1471-2164}, support = {BCRF-16-143 (RJS)//Breast Cancer Research Foundation/ ; NIH RO1CA178509//National Institutes of Health/ ; R01 CA207893/CA/NCI NIH HHS/United States ; R01 CA178509/CA/NCI NIH HHS/United States ; NIH RO1CA207893//National Institutes of Health/ ; }, abstract = {BACKGROUND: Translatomics data, particularly genome-wide ribosome profiling and polysome profiling, provide multiple levels of gene regulatory information that can be used to assess general transcription and translation, as well translational efficiency. The increasing popularity of these techniques has resulted in multiple algorithms to detect translational regulation, typically distributed in the form of command line tools that require a basic level of programming ability. Additionally, due to the static nature of current software, dynamic transcriptional and translational comparative analysis cannot be adequately achieved. In order to streamline hypothesis generation, investigators must have the ability to manipulate and interact with their data in real-time.

RESULTS: To address the lack of integration in current software, we introduce RIVET, Ribosomal Investigation and Visualization to Evaluate Translation, an R shiny based graphical user interface for translatomics data exploration and differential analysis. RIVET can analyze either microarray or RNA sequencing data from polysome profiling and ribosome profiling experiments. RIVET provides multiple choices for statistical analysis as well as integration of transcription, translation, and translational efficiency data analytics and the ability to visualize all results dynamically.

CONCLUSIONS: RIVET is a user-friendly tool designed for bench scientists with little to no programming background. RIVET facilitates the data analysis of translatomics data allowing for dynamic generation of results based on user-defined inputs and publication ready visualization. We expect RIVET will allow for scientists to efficiently make more comprehensive data observations that will lead to more robust hypothesis regarding translational regulation.}, } @article {pmid30409148, year = {2018}, author = {Abate, TW and Tareke, M and Tirfie, M}, title = {Self-care practices and associated factors among diabetes patients attending the outpatient department in Bahir Dar, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {800}, pmid = {30409148}, issn = {1756-0500}, abstract = {OBJECTIVE: The aim of this study was to assess diabetes self-care practice and associated factors among diabetes patients attending Felege-Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia.

RESULT: Prevalence of desirable self-care behaviors toward Diabetes Mellitus was 28.4% (95% CI 24.0-32.7%). There were significant association between the combined treatment modality of tablet with insulin (AOR: 2.72; 95% CI 1.01, 7.40), primary and secondary education level (AOR: 4.82; 95% CI 1.88, 12.35 and AOR: 3.08; 95% CI 1.26, 7.53, respectively). A considerable number of the patients had poor self-care practice, especially lack of social support and treatment modality, which have critical roles in controlling diabetes. Therefore, attention should be given to improve self-care practice.}, } @article {pmid30409146, year = {2018}, author = {Barik, M and Bhattacharjee, I and Ghosh, A and Chandra, G}, title = {Larvivorous potentiality of Puntius tetrazona and Hyphessobrycon rosaceus against Culex vishnui subgroup in laboratory and field based bioassay.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {804}, pmid = {30409146}, issn = {1756-0500}, abstract = {OBJECTIVES: This study assessed the predatory potentiality of two unexplored fishes, Puntius tetrazona and Hyphessobrycon rosaceus on Culex vishnui subgroup larvae in order to utilize natural resources to diminish mosquito population. Larval feeding rate was evaluated in laboratory under varying prey density and volume of water. The experiment was extended to semi field condition.

RESULTS: Puntius tetrazona and H. rosaceus consumed from 66 to 600 and from 87 to 718 Cx. vishnui larvae respectively in laboratory condition at 10 prey density levels (100-1000 larvae) at an increment of 100 larvae at 2 l water volume. In semi field condition, a 78% reduction in larval density was observed at day 30 post introduction of P. tetrazona, whereas 91% reduction was noted on day 21 for H. rosaceus and in the subsequent samples no mosquito larvae were found in ditches. Withdrawal of predators from the ditches resulted gradual increase in larval density. Laboratory and semi field bioassay of both the species indicated their potentiality as efficient mosquito larval predator though H. rosaceus exhibited better performance than P. tetrazona. It is recommended to utilize these natural resources to diminish mosquito population in the countries of their native range.}, } @article {pmid30409135, year = {2018}, author = {Okada, M and Yoshida, K and Nishijima, R and Michikawa, A and Motoi, Y and Sato, K and Takumi, S}, title = {RNA-seq analysis reveals considerable genetic diversity and provides genetic markers saturating all chromosomes in the diploid wild wheat relative Aegilops umbellulata.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {271}, pmid = {30409135}, issn = {1471-2229}, support = {No. 17H05842//Ministry of Education, Culture, Sports, Science and Technology/ ; No. 16H04862//Ministry of Education, Culture, Sports, Science and Technology/ ; No. JPMJPR15QB//Japan Science and Technology Agency/ ; }, mesh = {Chromosome Mapping ; Chromosomes, Plant/*genetics ; Diploidy ; Genetic Linkage/genetics ; Genome, Plant/*genetics ; Hordeum/genetics ; Plant Breeding ; Poaceae/genetics ; Triticum/*genetics ; }, abstract = {BACKGROUND: Aegilops umbellulata Zhuk. (2n = 14), a wild diploid wheat relative, has been the source of trait improvement in wheat breeding. Intraspecific genetic variation of Ae. umbellulata, however, has not been well studied and the genomic information in this species is limited.

RESULTS: To develop novel genetic markers distributed over all chromosomes of Ae. umbellulata and to evaluate its genetic diversity, we performed RNA sequencing of 12 representative accessions and reconstructed transcripts by de novo assembly of reads for each accession. A large number of single nucleotide polymorphisms (SNPs) and insertions/deletions (indels) were obtained and anchored to the pseudomolecules of Ae. tauschii and barley (Hordeum vulgare L.), which were regarded as virtual chromosomes of Ae. umbellulata. Interestingly, genetic diversity in Ae. umbellulata was higher than in Ae. tauschii, despite the narrow habitat of Ae. umbellulata. Comparative analyses of nucleotide polymorphisms between Ae. umbellulata and Ae. tauschii revealed no clear lineage differentiation and existence of alleles with rarer frequencies predominantly in Ae. umbellulata, with patterns clearly distinct from those in Ae. tauschii.

CONCLUSIONS: The anchored SNPs, covering all chromosomes, provide sufficient genetic markers between Ae. umbellulata accessions. The alleles with rarer frequencies might be the main source of the high genetic diversity in Ae. umbellulata.}, } @article {pmid30409115, year = {2018}, author = {Zhao, F and Sun, M and Zhang, W and Jiang, C and Teng, J and Sheng, W and Li, M and Zhang, A and Duan, Y and Xue, J}, title = {Comparative transcriptome analysis of roots, stems and leaves of Isodon amethystoides reveals candidate genes involved in Wangzaozins biosynthesis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {272}, pmid = {30409115}, issn = {1471-2229}, mesh = {Isodon/*genetics/metabolism ; Molecular Sequence Annotation ; Plant Leaves/*genetics/metabolism ; Plant Roots/*genetics/metabolism ; Plant Stems/*genetics/metabolism ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Isodon amethystoides (Ben-th) Cy Wu et Hsuan is an important traditional medicinal plant endowed with pharmacological properties effective in the treatment of various diseases, including pulmonary tuberculosis. The tetracyclic diterpenoids, Wangzaozins (Wangzaozin A, glaucocalyxin A, glaucocalyxin B), are the major bioactive compounds of I. amethystoides. However, the molecular information about the biosynthesis of these compounds still remains unclear.

RESULTS: An examination of the accumulated levels of Wangzaozins in I. amethystoides revealed considerable variations in the root, stem, and leaf tissues of this plant, indicating possible differences in metabolite biosynthesis and accumulation among various tissues. To better elucidate the tetracyclic diterpenoid biosynthesis pathway, we generated transcriptome sequences from the root, stem, and leaf tissues, and performed de novo sequence assembly, yielding 230,974 transcripts and 114,488 unigenes, with average N50 lengths of 1914 and 1241 bp, respectively. Putative functions could be assigned to 73,693 transcripts (31.9%) based on BLAST searches against annotation databases, including GO, KEGG, Swiss-Prot, NR, and Pfam. Moreover, the candidate genes involving in the diterpenoid biosynthesis, such as CPS, KSL, were also analyzed. The expression profiles of eight transcripts, involving the tetracyclic diterpenoid biosynthesis, were validated in different I. amethystoides tissues by qRT-PCR, unraveling the gene expression profile of the pathway. The differential expressions of ISPD, ISPF and ISPH (MEP pathway), and IaCPS and IaKSL (diterpenoid pathway) candidate genes in leaves and roots, may contribute to the high accumulation of Wangzaozins in I. amethystoides leaves.

CONCLUSION: The genomic dataset and analyses reported here lay the foundations for further research on this important medicinal plant.}, } @article {pmid30409110, year = {2018}, author = {Kodama, M and Brinch-Pedersen, H and Sharma, S and Holme, IB and Joernsgaard, B and Dzhanfezova, T and Amby, DB and Vieira, FG and Liu, S and Gilbert, MTP}, title = {Identification of transcription factor genes involved in anthocyanin biosynthesis in carrot (Daucus carota L.) using RNA-Seq.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {811}, pmid = {30409110}, issn = {1471-2164}, support = {4105-00006A//Innovation Fund Denmark/ ; }, abstract = {BACKGROUND: Anthocyanins are water-soluble colored flavonoids present in multiple organs of various plant species including flowers, fruits, leaves, stems and roots. DNA-binding R2R3-MYB transcription factors, basic helix-loop-helix (bHLH) transcription factors, and WD40 repeat proteins are known to form MYB-bHLH-WD repeat (MBW) complexes, which activates the transcription of structural genes in the anthocyanin pathway. Although black cultivars of carrots (Daucus carota L.) can accumulate large quantities of anthocyanin in their storage roots, the regulatory genes responsible for their biosynthesis are not well characterized. The current study aimed to analyze global transcription profiles based on RNA sequencing (RNA-Seq), and mine MYB, bHLH and WD40 genes that may function as positive or negative regulators in the carrot anthocyanin biosynthesis pathways.

RESULTS: RNA was isolated from differently colored calli, as well as tissue samples from taproots of various black carrot cultivars across the course of development, and gene expression levels of colored and non-colored tissue and callus samples were compared. The expression of 32 MYB, bHLH and WD40 genes were significantly correlated with anthocyanin content in black carrot taproot. Of those, 11 genes were consistently up- or downregulated in a purple color-specific manner across various calli and cultivar comparisons. The expression of 10 out of these 11 genes was validated using real-time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR).

CONCLUSIONS: The results of this study provide insights into regulatory genes that may be responsible for carrot anthocyanin biosynthesis, and suggest that future focus on them may help improve our overall understanding of the anthocyanin synthesis pathway.}, } @article {pmid30407903, year = {2019}, author = {Paek, J and Shin, Y and Kook, JK and Chang, YH}, title = {Blautia argi sp. nov., a new anaerobic bacterium isolated from dog faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {33-38}, doi = {10.1099/ijsem.0.002981}, pmid = {30407903}, issn = {1466-5034}, abstract = {Two isolates of a Gram-positive, non-motile, coccoid or oval-shaped anaerobic bacterium, designated strains N6H1-15T and YH1_16, were isolated from faecal samples obtained from a mature dog. Analysis of 16S rRNA gene sequences indicated that the isolates belonged to the Blautia coccoidesrRNA gene group (cluster XIVa) and were closely related to Blautia hansenii KCTC 5951T, Blautia stercoris KCTC 5981T, Blautia producta producta KCTC 3695T and B. coccoides DSM 15327T, with 96.7, 94.4, 94.2 and 93.9 % sequence similarity, respectively. The two isolates contained m-diaminopimelic acid within their peptidoglycans. The major polar lipids were diphosphatidylglycerol and phosphatidylglycerol, and the major fatty acids were C16 : 0 (18.5 %), C16 : 0 (18.0 %) and C18 : 1cis 9 (16.2 %). The predominant metabolic end products of glucose fermentation were acetic and lactic acids, and the G+C content was 44.2 mol%. Thus, the polyphasic data suggest that the two new isolates represent a new species, proposed as Blautia argi sp. nov. The type strain is N6H1-15T (=KCTC 15426=JCM 31394).}, } @article {pmid30407540, year = {2018}, author = {Kado, T and Innan, H}, title = {Horizontal Gene Transfer in Five Parasite Plant Species in Orobanchaceae.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3196-3210}, doi = {10.1093/gbe/evy219}, pmid = {30407540}, issn = {1759-6653}, abstract = {We sequenced genomes of five parasite species in family Orobanchaceae to explore the evolutionary role of horizontal gene transfer in plants. Orobanche minor and Aeginetia indica are obligate parasites with no photosynthetic activity, whereas the other three (Pedicularis keiskei, Phtheirospermum japonicum, and Melampyrum roseum) are facultative parasites. By using reference genome sequences and/or transcriptomes of 14 species from Fabaceae and Poaceae, their major host families, we detected 106 horizontally transferred genes (HGT genes), only in the genomes of the two obligate parasites (22 and 84 for Oro. minor and Ae. indica, respectively), whereas none in the three facultative parasites. The HGT genes, respectively, account for roughly 0.1% and 0.2% of the coding genes in the two species. We found that almost all HGT genes retained introns at the same locations as their homologs in potential host species, indicating a crucial role of DNA-mediated gene transfer, rather than mRNA mediated retro transfer. Furthermore, some of the HGT genes might have transferred simultaneously because they located very closely in the host reference genome, indicating that the length of transferred DNA could exceed 100 kb. We confirmed that almost all introns are spliced in the current genome of the parasite species, and that about half HGT genes do not have any missense mutations or frameshift-causing indels, suggesting that some HGT genes may be still functional. Evolutionary analyses revealed that the nonsynonymous-synonymous substitution ratio is on average elevated on the lineage leading to HGT genes, due to either relaxation of selection or positive selection.}, } @article {pmid30407531, year = {2018}, author = {Artur, MAS and Zhao, T and Ligterink, W and Schranz, ME and Hilhorst, HWM}, title = {Dissecting the genomic diversification of LATE EMBRYOGENESIS ABUNDANT (LEA) protein gene families in plants.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evy248}, pmid = {30407531}, issn = {1759-6653}, abstract = {Late Embryogenesis Abundant (LEA) proteins include eight multi-gene families that are expressed in response to water loss during seed maturation and in vegetative tissues of desiccation tolerant species. To elucidate LEA proteins evolution and diversification, we performed a comprehensive synteny and phylogenetic analyses of the eight gene families across 60 complete plant genomes. Our integrated comparative genomic approach revealed that synteny conservation and diversification contributed to LEA family expansion and functional diversification in plants. We provide examples that: 1) the genomic diversification of the Dehydrin family contributed to differential evolution of amino acid sequences, protein biochemical properties, and gene expression patterns, and led to the appearance of a novel functional motif in angiosperms; 2) ancient genomic diversification contributed to the evolution of distinct intrinsically disordered regions of LEA_1 proteins; 3) recurrent tandem-duplications contributed to the large expansion of LEA_2; and, 4) dynamic synteny diversification played a role on the evolution of LEA_4 and its function on plant desiccation tolerance. Taken together, these results show that multiple evolutionary mechanisms have not only led to genomic diversification, but also to structural and functional plasticity among LEA proteins which have jointly contributed to the adaptation of plants to water-limiting environments.}, } @article {pmid30406864, year = {2018}, author = {Fulka, H and Langerova, A}, title = {Nucleoli in embryos: a central structural platform for embryonic chromatin remodeling?.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9590-3}, pmid = {30406864}, issn = {1573-6849}, support = {17-08605S//Grantová Agentura České Republiky/ ; }, abstract = {Nucleoli are the site of ribosomal RNA production and subunit assembly. In contrast to active nucleoli in somatic cells, where three basic sub-compartments can be observed, mammalian oocytes and early embryos contain atypical nucleoli termed "nucleolus-like bodies" or "nucleolus precursor bodies", respectively. Unlike their somatic counterparts, these structures are composed of dense homogenous fibrillar material and exhibit no polymerase activity. Irrespective of these unusual properties, they have been shown to be absolutely essential for embryonic development, as their microsurgical removal results in developmental arrest. Historically, nucleolus-like and nucleolus precursor bodies have been perceived as passive storage sites of nucleolar material, which is gradually utilized by embryos to construct fully functional nucleoli once they have activated their genome and have started to produce ribosomes. For decades, researchers have been trying to elucidate the composition of these organelles and provide the evidence for their repository role. However, only recently has it become clear that the function of these atypical nucleoli is altogether different, and rather than being involved in ribosome biogenesis, they participate in parental chromatin remodeling, and strikingly, the artificial introduction of a single NPB component is sufficient to rescue the developmental arrest elicited by the NPB removal. In this review, we will describe and summarize the experiments that led to the change in our understanding of these unique structures.}, } @article {pmid30405246, year = {2018}, author = {Ramanjulu, JM and Pesiridis, GS and Yang, J and Concha, N and Singhaus, R and Zhang, SY and Tran, JL and Moore, P and Lehmann, S and Eberl, HC and Muelbaier, M and Schneck, JL and Clemens, J and Adam, M and Mehlmann, J and Romano, J and Morales, A and Kang, J and Leister, L and Graybill, TL and Charnley, AK and Ye, G and Nevins, N and Behnia, K and Wolf, AI and Kasparcova, V and Nurse, K and Wang, L and Li, Y and Klein, M and Hopson, CB and Guss, J and Bantscheff, M and Bergamini, G and Reilly, MA and Lian, Y and Duffy, KJ and Adams, J and Foley, KP and Gough, PJ and Marquis, RW and Smothers, J and Hoos, A and Bertin, J}, title = {Design of amidobenzimidazole STING receptor agonists with systemic activity.}, journal = {Nature}, volume = {564}, number = {7736}, pages = {439-443}, doi = {10.1038/s41586-018-0705-y}, pmid = {30405246}, issn = {1476-4687}, abstract = {Stimulator of interferon genes (STING) is a receptor in the endoplasmic reticulum that propagates innate immune sensing of cytosolic pathogen-derived and self DNA1. The development of compounds that modulate STING has recently been the focus of intense research for the treatment of cancer and infectious diseases and as vaccine adjuvants2. To our knowledge, current efforts are focused on the development of modified cyclic dinucleotides that mimic the endogenous STING ligand cGAMP; these have progressed into clinical trials in patients with solid accessible tumours amenable to intratumoral delivery3. Here we report the discovery of a small molecule STING agonist that is not a cyclic dinucleotide and is systemically efficacious for treating tumours in mice. We developed a linking strategy to synergize the effect of two symmetry-related amidobenzimidazole (ABZI)-based compounds to create linked ABZIs (diABZIs) with enhanced binding to STING and cellular function. Intravenous administration of a diABZI STING agonist to immunocompetent mice with established syngeneic colon tumours elicited strong anti-tumour activity, with complete and lasting regression of tumours. Our findings represent a milestone in the rapidly growing field of immune-modifying cancer therapies.}, } @article {pmid30405245, year = {2018}, author = {Cronin, SJF and Seehus, C and Weidinger, A and Talbot, S and Reissig, S and Seifert, M and Pierson, Y and McNeill, E and Longhi, MS and Turnes, BL and Kreslavsky, T and Kogler, M and Hoffmann, D and Ticevic, M and da Luz Scheffer, D and Tortola, L and Cikes, D and Jais, A and Rangachari, M and Rao, S and Paolino, M and Novatchkova, M and Aichinger, M and Barrett, L and Latremoliere, A and Wirnsberger, G and Lametschwandtner, G and Busslinger, M and Zicha, S and Latini, A and Robson, SC and Waisman, A and Andrews, N and Costigan, M and Channon, KM and Weiss, G and Kozlov, AV and Tebbe, M and Johnsson, K and Woolf, CJ and Penninger, JM}, title = {The metabolite BH4 controls T cell proliferation in autoimmunity and cancer.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {564-568}, doi = {10.1038/s41586-018-0701-2}, pmid = {30405245}, issn = {1476-4687}, support = {R01 DK108894/DK/NIDDK NIH HHS/United States ; R21 CA221702/CA/NCI NIH HHS/United States ; R37 NS039518/NS/NINDS NIH HHS/United States ; R35 NS105076/NS/NINDS NIH HHS/United States ; }, abstract = {Genetic regulators and environmental stimuli modulate T cell activation in autoimmunity and cancer. The enzyme co-factor tetrahydrobiopterin (BH4) is involved in the production of monoamine neurotransmitters, the generation of nitric oxide, and pain1,2. Here we uncover a link between these processes, identifying a fundamental role for BH4 in T cell biology. We find that genetic inactivation of GTP cyclohydrolase 1 (GCH1, the rate-limiting enzyme in the synthesis of BH4) and inhibition of sepiapterin reductase (the terminal enzyme in the synthetic pathway for BH4) severely impair the proliferation of mature mouse and human T cells. BH4 production in activated T cells is linked to alterations in iron metabolism and mitochondrial bioenergetics. In vivo blockade of BH4 synthesis abrogates T-cell-mediated autoimmunity and allergic inflammation, and enhancing BH4 levels through GCH1 overexpression augments responses by CD4- and CD8-expressing T cells, increasing their antitumour activity in vivo. Administration of BH4 to mice markedly reduces tumour growth and expands the population of intratumoral effector T cells. Kynurenine-a tryptophan metabolite that blocks antitumour immunity-inhibits T cell proliferation in a manner that can be rescued by BH4. Finally, we report the development of a potent SPR antagonist for possible clinical use. Our data uncover GCH1, SPR and their downstream metabolite BH4 as critical regulators of T cell biology that can be readily manipulated to either block autoimmunity or enhance anticancer immunity.}, } @article {pmid30405244, year = {2018}, author = {Shen, MW and Arbab, M and Hsu, JY and Worstell, D and Culbertson, SJ and Krabbe, O and Cassa, CA and Liu, DR and Gifford, DK and Sherwood, RI}, title = {Predictable and precise template-free CRISPR editing of pathogenic variants.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {646-651}, doi = {10.1038/s41586-018-0686-x}, pmid = {30405244}, issn = {1476-4687}, support = {1R01HG010372/NH/NIH HHS/United States ; RM1 HG009490/HG/NHGRI NIH HHS/United States ; R01 EB022376/EB/NIBIB NIH HHS/United States ; R35 GM118062/GM/NIGMS NIH HHS/United States ; R01 HG008363/HG/NHGRI NIH HHS/United States ; R01 HG008754/HG/NHGRI NIH HHS/United States ; K01 DK101684/DK/NIDDK NIH HHS/United States ; }, abstract = {Following Cas9 cleavage, DNA repair without a donor template is generally considered stochastic, heterogeneous and impractical beyond gene disruption. Here, we show that template-free Cas9 editing is predictable and capable of precise repair to a predicted genotype, enabling correction of disease-associated mutations in humans. We constructed a library of 2,000 Cas9 guide RNAs paired with DNA target sites and trained inDelphi, a machine learning model that predicts genotypes and frequencies of 1- to 60-base-pair deletions and 1-base-pair insertions with high accuracy (r = 0.87) in five human and mouse cell lines. inDelphi predicts that 5-11% of Cas9 guide RNAs targeting the human genome are 'precise-50', yielding a single genotype comprising greater than or equal to 50% of all major editing products. We experimentally confirmed precise-50 insertions and deletions in 195 human disease-relevant alleles, including correction in primary patient-derived fibroblasts of pathogenic alleles to wild-type genotype for Hermansky-Pudlak syndrome and Menkes disease. This study establishes an approach for precise, template-free genome editing.}, } @article {pmid30405243, year = {2018}, author = {Lauber, F and Deme, JC and Lea, SM and Berks, BC}, title = {Type 9 secretion system structures reveal a new protein transport mechanism.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {77-82}, doi = {10.1038/s41586-018-0693-y}, pmid = {30405243}, issn = {1476-4687}, support = {107929/Z/15/Z//Wellcome Trust/United Kingdom ; 100298/Z/12/Z//Wellcome Trust/United Kingdom ; 201536/Z/16/Z//Wellcome Trust/United Kingdom ; }, abstract = {The type 9 secretion system (T9SS) is the protein export pathway of bacteria of the Gram-negative Fibrobacteres-Chlorobi-Bacteroidetes superphylum and is an essential determinant of pathogenicity in severe periodontal disease. The central element of the T9SS is a so-far uncharacterized protein-conducting translocon located in the bacterial outer membrane. Here, using cryo-electron microscopy, we provide structural evidence that the translocon is the T9SS protein SprA. SprA forms an extremely large (36-strand) single polypeptide transmembrane β-barrel. The barrel pore is capped on the extracellular end, but has a lateral opening to the external membrane surface. Structures of SprA bound to different components of the T9SS show that partner proteins control access to the lateral opening and to the periplasmic end of the pore. Our results identify a protein transporter with a distinctive architecture that uses an alternating access mechanism in which the two ends of the protein-conducting channel are open at different times.}, } @article {pmid30405242, year = {2018}, author = {Aubert, M and Setiawan, P and Oktaviana, AA and Brumm, A and Sulistyarto, PH and Saptomo, EW and Istiawan, B and Ma'rifat, TA and Wahyuono, VN and Atmoko, FT and Zhao, JX and Huntley, J and Taçon, PSC and Howard, DL and Brand, HEA}, title = {Palaeolithic cave art in Borneo.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {254-257}, doi = {10.1038/s41586-018-0679-9}, pmid = {30405242}, issn = {1476-4687}, abstract = {Figurative cave paintings from the Indonesian island of Sulawesi date to at least 35,000 years ago (ka) and hand-stencil art from the same region has a minimum date of 40 ka1. Here we show that similar rock art was created during essentially the same time period on the adjacent island of Borneo. Uranium-series analysis of calcium carbonate deposits that overlie a large reddish-orange figurative painting of an animal at Lubang Jeriji Saléh-a limestone cave in East Kalimantan, Indonesian Borneo-yielded a minimum date of 40 ka, which to our knowledge is currently the oldest date for figurative artwork from anywhere in the world. In addition, two reddish-orange-coloured hand stencils from the same site each yielded a minimum uranium-series date of 37.2 ka, and a third hand stencil of the same hue has a maximum date of 51.8 ka. We also obtained uranium-series determinations for cave art motifs from Lubang Jeriji Saléh and three other East Kalimantan karst caves, which enable us to constrain the chronology of a distinct younger phase of Pleistocene rock art production in this region. Dark-purple hand stencils, some of which are decorated with intricate motifs, date to about 21-20 ka and a rare Pleistocene depiction of a human figure-also coloured dark purple-has a minimum date of 13.6 ka. Our findings show that cave painting appeared in eastern Borneo between 52 and 40 ka and that a new style of parietal art arose during the Last Glacial Maximum. It is now evident that a major Palaeolithic cave art province existed in the eastern extremity of continental Eurasia and in adjacent Wallacea from at least 40 ka until the Last Glacial Maximum, which has implications for understanding how early rock art traditions emerged, developed and spread in Pleistocene Southeast Asia and further afield.}, } @article {pmid30405241, year = {2018}, author = {Kern, J and Chatterjee, R and Young, ID and Fuller, FD and Lassalle, L and Ibrahim, M and Gul, S and Fransson, T and Brewster, AS and Alonso-Mori, R and Hussein, R and Zhang, M and Douthit, L and de Lichtenberg, C and Cheah, MH and Shevela, D and Wersig, J and Seuffert, I and Sokaras, D and Pastor, E and Weninger, C and Kroll, T and Sierra, RG and Aller, P and Butryn, A and Orville, AM and Liang, M and Batyuk, A and Koglin, JE and Carbajo, S and Boutet, S and Moriarty, NW and Holton, JM and Dobbek, H and Adams, PD and Bergmann, U and Sauter, NK and Zouni, A and Messinger, J and Yano, J and Yachandra, VK}, title = {Structures of the intermediates of Kok's photosynthetic water oxidation clock.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {421-425}, doi = {10.1038/s41586-018-0681-2}, pmid = {30405241}, issn = {1476-4687}, support = {R01 GM126289/GM/NIGMS NIH HHS/United States ; GM117126/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; GM116423-02/GM/NIGMS NIH HHS/United States ; R01 GM110501/GM/NIGMS NIH HHS/United States ; R01 GM124149/GM/NIGMS NIH HHS/United States ; R01 GM117126/GM/NIGMS NIH HHS/United States ; P30 GM124169/GM/NIGMS NIH HHS/United States ; R01 GM055302/GM/NIGMS NIH HHS/United States ; }, abstract = {Inspired by the period-four oscillation in flash-induced oxygen evolution of photosystem II discovered by Joliot in 1969, Kok performed additional experiments and proposed a five-state kinetic model for photosynthetic oxygen evolution, known as Kok's S-state clock or cycle1,2. The model comprises four (meta)stable intermediates (S0, S1, S2 and S3) and one transient S4 state, which precedes dioxygen formation occurring in a concerted reaction from two water-derived oxygens bound at an oxo-bridged tetra manganese calcium (Mn4CaO5) cluster in the oxygen-evolving complex3-7. This reaction is coupled to the two-step reduction and protonation of the mobile plastoquinone QB at the acceptor side of PSII. Here, using serial femtosecond X-ray crystallography and simultaneous X-ray emission spectroscopy with multi-flash visible laser excitation at room temperature, we visualize all (meta)stable states of Kok's cycle as high-resolution structures (2.04-2.08 Å). In addition, we report structures of two transient states at 150 and 400 µs, revealing notable structural changes including the binding of one additional 'water', Ox, during the S2→S3 state transition. Our results suggest that one water ligand to calcium (W3) is directly involved in substrate delivery. The binding of the additional oxygen Ox in the S3 state between Ca and Mn1 supports O-O bond formation mechanisms involving O5 as one substrate, where Ox is either the other substrate oxygen or is perfectly positioned to refill the O5 position during O2 release. Thus, our results exclude peroxo-bond formation in the S3 state, and the nucleophilic attack of W3 onto W2 is unlikely.}, } @article {pmid30405240, year = {2018}, author = {Vander Weele, CM and Siciliano, CA and Matthews, GA and Namburi, P and Izadmehr, EM and Espinel, IC and Nieh, EH and Schut, EHS and Padilla-Coreano, N and Burgos-Robles, A and Chang, CJ and Kimchi, EY and Beyeler, A and Wichmann, R and Wildes, CP and Tye, KM}, title = {Dopamine enhances signal-to-noise ratio in cortical-brainstem encoding of aversive stimuli.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {397-401}, doi = {10.1038/s41586-018-0682-1}, pmid = {30405240}, issn = {1476-4687}, support = {R01 MH102441/MH/NIMH NIH HHS/United States ; DP2-DK-102256-01/DK/NIDDK NIH HHS/United States ; DP1 AT009925/AT/NCCIH NIH HHS/United States ; DP1 AT009925/AT/NCCIH NIH HHS/United States ; T32 GM007484/GM/NIGMS NIH HHS/United States ; F32 MH111216/MH/NIMH NIH HHS/United States ; K99 DA045103/DA/NIDA NIH HHS/United States ; }, abstract = {Dopamine modulates medial prefrontal cortex (mPFC) activity to mediate diverse behavioural functions1,2; however, the precise circuit computations remain unknown. One potentially unifying model by which dopamine may underlie a diversity of functions is by modulating the signal-to-noise ratio in subpopulations of mPFC neurons3-6, where neural activity conveying sensory information (signal) is amplified relative to spontaneous firing (noise). Here we demonstrate that dopamine increases the signal-to-noise ratio of responses to aversive stimuli in mPFC neurons projecting to the dorsal periaqueductal grey (dPAG). Using an electrochemical approach, we reveal the precise time course of pinch-evoked dopamine release in the mPFC, and show that mPFC dopamine biases behavioural responses to aversive stimuli. Activation of mPFC-dPAG neurons is sufficient to drive place avoidance and defensive behaviours. mPFC-dPAG neurons display robust shock-induced excitations, as visualized by single-cell, projection-defined microendoscopic calcium imaging. Finally, photostimulation of dopamine terminals in the mPFC reveals an increase in the signal-to-noise ratio in mPFC-dPAG responses to aversive stimuli. Together, these data highlight how dopamine in the mPFC can selectively route sensory information to specific downstream circuits, representing a potential circuit mechanism for valence processing.}, } @article {pmid30405239, year = {2018}, author = {Manolaridis, I and Jackson, SM and Taylor, NMI and Kowal, J and Stahlberg, H and Locher, KP}, title = {Cryo-EM structures of a human ABCG2 mutant trapped in ATP-bound and substrate-bound states.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {426-430}, doi = {10.1038/s41586-018-0680-3}, pmid = {30405239}, issn = {1476-4687}, abstract = {ABCG2 is a transporter protein of the ATP-binding-cassette (ABC) family that is expressed in the plasma membrane in cells of various tissues and tissue barriers, including the blood-brain, blood-testis and maternal-fetal barriers1-4. Powered by ATP, it translocates endogenous substrates, affects the pharmacokinetics of many drugs and protects against a wide array of xenobiotics, including anti-cancer drugs5-12. Previous studies have revealed the architecture of ABCG2 and the structural basis of its inhibition by small molecules and antibodies13,14. However, the mechanisms of substrate recognition and ATP-driven transport are unknown. Here we present high-resolution cryo-electron microscopy (cryo-EM) structures of human ABCG2 in a substrate-bound pre-translocation state and an ATP-bound post-translocation state. For both structures, we used a mutant containing a glutamine replacing the catalytic glutamate (ABCG2EQ), which resulted in reduced ATPase and transport rates and facilitated conformational trapping for structural studies. In the substrate-bound state, a single molecule of estrone-3-sulfate (E1S) is bound in a central, hydrophobic and cytoplasm-facing cavity about halfway across the membrane. Only one molecule of E1S can bind in the observed binding mode. In the ATP-bound state, the substrate-binding cavity has collapsed while an external cavity has opened to the extracellular side of the membrane. The ATP-induced conformational changes include rigid-body shifts of the transmembrane domains, pivoting of the nucleotide-binding domains (NBDs), and a change in the relative orientation of the NBD subdomains. Mutagenesis and in vitro characterization of transport and ATPase activities demonstrate the roles of specific residues in substrate recognition, including a leucine residue that forms a 'plug' between the two cavities. Our results show how ABCG2 harnesses the energy of ATP binding to extrude E1S and other substrates, and suggest that the size and binding affinity of compounds are important for distinguishing substrates from inhibitors.}, } @article {pmid30405238, year = {2018}, author = {Luo, J and Wang, X and Li, S and Liu, J and Guo, Y and Niu, G and Yao, L and Fu, Y and Gao, L and Dong, Q and Zhao, C and Leng, M and Ma, F and Liang, W and Wang, L and Jin, S and Han, J and Zhang, L and Etheridge, J and Wang, J and Yan, Y and Sargent, EH and Tang, J}, title = {Efficient and stable emission of warm-white light from lead-free halide double perovskites.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {541-545}, doi = {10.1038/s41586-018-0691-0}, pmid = {30405238}, issn = {1476-4687}, support = {DE-EE0006712//US Department of Energy/International ; DMR-1807818//National Science Foundation/International ; DE-AC02-05CH11231//US Department of Energy/International ; }, abstract = {Lighting accounts for one-fifth of global electricity consumption1. Single materials with efficient and stable white-light emission are ideal for lighting applications, but photon emission covering the entire visible spectrum is difficult to achieve using a single material. Metal halide perovskites have outstanding emission properties2,3; however, the best-performing materials of this type contain lead and have unsatisfactory stability. Here we report a lead-free double perovskite that exhibits efficient and stable white-light emission via self-trapped excitons that originate from the Jahn-Teller distortion of the AgCl6 octahedron in the excited state. By alloying sodium cations into Cs2AgInCl6, we break the dark transition (the inversion-symmetry-induced parity-forbidden transition) by manipulating the parity of the wavefunction of the self-trapped exciton and reduce the electronic dimensionality of the semiconductor4. This leads to an increase in photoluminescence efficiency by three orders of magnitude compared to pure Cs2AgInCl6. The optimally alloyed Cs2(Ag0.60Na0.40)InCl6 with 0.04 per cent bismuth doping emits warm-white light with 86 ± 5 per cent quantum efficiency and works for over 1,000 hours. We anticipate that these results will stimulate research on single-emitter-based white-light-emitting phosphors and diodes for next-generation lighting and display technologies.}, } @article {pmid30405237, year = {2018}, author = {Rainò, G and Becker, MA and Bodnarchuk, MI and Mahrt, RF and Kovalenko, MV and Stöferle, T}, title = {Superfluorescence from lead halide perovskite quantum dot superlattices.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {671-675}, doi = {10.1038/s41586-018-0683-0}, pmid = {30405237}, issn = {1476-4687}, abstract = {An ensemble of emitters can behave very differently from its individual constituents when they interact coherently via a common light field. After excitation of such an ensemble, collective coupling can give rise to a many-body quantum phenomenon that results in short, intense bursts of light-so-called superfluorescence1. Because this phenomenon requires a fine balance of interactions between the emitters and their decoupling from the environment, together with close identity of the individual emitters, superfluorescence has thus far been observed only in a limited number of systems, such as certain atomic and molecular gases and a few solid-state systems2-7. The generation of superfluorescent light in colloidal nanocrystals (which are bright photonic sources practically suited for optoelectronics8,9) has been precluded by inhomogeneous emission broadening, low oscillator strength, and fast exciton dephasing. Here we show that caesium lead halide (CsPbX3, X = Cl, Br) perovskite nanocrystals10-13 that are self-organized into highly ordered three-dimensional superlattices exhibit key signatures of superfluorescence. These are dynamically red-shifted emission with more than 20-fold accelerated radiative decay, extension of the first-order coherence time by more than a factor of four, photon bunching, and delayed emission pulses with Burnham-Chiao ringing behaviour14 at high excitation density. These mesoscopically extended coherent states could be used to boost the performance of opto-electronic devices15 and enable entangled multi-photon quantum light sources16,17.}, } @article {pmid30405236, year = {2018}, author = {Ménez, B and Pisapia, C and Andreani, M and Jamme, F and Vanbellingen, QP and Brunelle, A and Richard, L and Dumas, P and Réfrégiers, M}, title = {Abiotic synthesis of amino acids in the recesses of the oceanic lithosphere.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {59-63}, doi = {10.1038/s41586-018-0684-z}, pmid = {30405236}, issn = {1476-4687}, abstract = {Abiotic hydrocarbons and carboxylic acids are known to be formed on Earth, notably during the hydrothermal alteration of mantle rocks. Although the abiotic formation of amino acids has been predicted both from experimental studies and thermodynamic calculations, its occurrence has not been demonstrated in terrestrial settings. Here, using a multimodal approach that combines high-resolution imaging techniques, we obtain evidence for the occurrence of aromatic amino acids formed abiotically and subsequently preserved at depth beneath the Atlantis Massif (Mid-Atlantic Ridge). These aromatic amino acids may have been formed through Friedel-Crafts reactions catalysed by an iron-rich saponite clay during a late alteration stage of the massif serpentinites. Demonstrating the potential of fluid-rock interactions in the oceanic lithosphere to generate amino acids abiotically gives credence to the hydrothermal theory for the origin of life, and may shed light on ancient metabolisms and the functioning of the present-day deep biosphere.}, } @article {pmid30405235, year = {2018}, author = {}, title = {Farewell to Kepler, India's neutrino observatory and an Ebola warning.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {160-161}, doi = {10.1038/d41586-018-07288-y}, pmid = {30405235}, issn = {1476-4687}, } @article {pmid30405234, year = {2018}, author = {Eisenstein, M}, title = {Ulcerative colitis: towards remission.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {S33}, doi = {10.1038/d41586-018-07276-2}, pmid = {30405234}, issn = {1476-4687}, } @article {pmid30405233, year = {2018}, author = {Eisenstein, M}, title = {Gut reaction.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {S34-S35}, doi = {10.1038/d41586-018-07277-1}, pmid = {30405233}, issn = {1476-4687}, } @article {pmid30405232, year = {2018}, author = {Powell, K}, title = {How biologists are creating life-like cells from scratch.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {172-175}, doi = {10.1038/d41586-018-07289-x}, pmid = {30405232}, issn = {1476-4687}, } @article {pmid30405231, year = {2018}, author = {}, title = {Bottom-up biology.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {171}, doi = {10.1038/d41586-018-07290-4}, pmid = {30405231}, issn = {1476-4687}, } @article {pmid30405229, year = {2018}, author = {Schiermeier, Q}, title = {Why a European agency post can be an excellent destination for researchers.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {281-283}, doi = {10.1038/d41586-018-07296-y}, pmid = {30405229}, issn = {1476-4687}, } @article {pmid30405228, year = {2018}, author = {Eigen, C and Glidden, JAP and Lopes, R and Cornell, EA and Smith, RP and Hadzibabic, Z}, title = {Universal prethermal dynamics of Bose gases quenched to unitarity.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {221-224}, doi = {10.1038/s41586-018-0674-1}, pmid = {30405228}, issn = {1476-4687}, abstract = {Understanding strongly correlated phases of matter, such as the quark-gluon plasma and neutron stars, and in particular the dynamics of such systems, for example, following a Hamiltonian quench (a sudden change in some Hamiltonian parameter, such as the strength of interparticle interactions) is a fundamental challenge in modern physics. Ultracold atomic gases are excellent quantum simulators for these problems, owing to their tunable interparticle interactions and experimentally resolvable intrinsic timescales. In particular, they provide access to the unitary regime, in which the interactions are as strong as allowed by quantum mechanics. This regime has been extensively studied in Fermi gases1,2. The less-explored unitary Bose gases3-11 offer possibilities12 such as universal physics controlled solely by the gas density13,14 and new forms of superfluidity15-17. Here, through momentum- and time-resolved studies, we explore degenerate and thermal homogeneous Bose gases quenched to unitarity. In degenerate samples, we observe universal post-quench dynamics in agreement with the emergence of a prethermal state18-24 with a universal non-zero condensed fraction22,24. In thermal gases, the dynamic and thermodynamic properties generally depend on the gas density and the temperature, but we find that they can still be expressed in terms of universal dimensionless functions. Surprisingly, we find that the total quench-induced correlation energy is independent of the gas temperature. These measurements provide quantitative benchmarks and challenges for the theory of unitary Bose gases.}, } @article {pmid30405227, year = {2018}, author = {Erne, S and Bücker, R and Gasenzer, T and Berges, J and Schmiedmayer, J}, title = {Universal dynamics in an isolated one-dimensional Bose gas far from equilibrium.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {225-229}, doi = {10.1038/s41586-018-0667-0}, pmid = {30405227}, issn = {1476-4687}, abstract = {Understanding the behaviour of isolated quantum systems far from equilibrium and their equilibration is one of the most pressing problems in quantum many-body physics1,2. There is strong theoretical evidence that sufficiently far from equilibrium a wide variety of systems-including the early Universe after inflation3-6, quark-gluon matter generated in heavy-ion collisions7-9, and cold quantum gases4,10-14-exhibit universal scaling in time and space during their evolution, independent of their initial state or microscale properties. However, direct experimental evidence is lacking. Here we demonstrate universal scaling in the time-evolving momentum distribution of an isolated, far-from-equilibrium, one-dimensional Bose gas, which emerges from a three-dimensional ultracold Bose gas by means of a strong cooling quench. Within the scaling regime, the time evolution of the system at low momenta is described by a time-independent, universal function and a single scaling exponent. The non-equilibrium scaling describes the transport of an emergent conserved quantity towards low momenta, which eventually leads to the build-up of a quasi-condensate. Our results establish universal scaling dynamics in an isolated quantum many-body system, which is a crucial step towards characterizing time evolution far from equilibrium in terms of universality classes. Universality would open the possibility of using, for example, cold-atom set-ups at the lowest energies to simulate important aspects of the dynamics of currently inaccessible systems at the highest energies, such as those encountered in the inflationary early Universe.}, } @article {pmid30405226, year = {2018}, author = {Prüfer, M and Kunkel, P and Strobel, H and Lannig, S and Linnemann, D and Schmied, CM and Berges, J and Gasenzer, T and Oberthaler, MK}, title = {Observation of universal dynamics in a spinor Bose gas far from equilibrium.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {217-220}, doi = {10.1038/s41586-018-0659-0}, pmid = {30405226}, issn = {1476-4687}, abstract = {Predicting the dynamics of quantum systems far from equilibrium represents one of the most challenging problems in theoretical many-body physics1,2. While the evolution of a many-body system is in general intractable in all its details, relevant observables can become insensitive to microscopic system parameters and initial conditions. This is the basis of the phenomenon of universality. Far from equilibrium, universality is identified through the scaling of the spatio-temporal evolution of the system, captured by universal exponents and functions. Theoretically, this has been studied in examples as different as the reheating process in inflationary Universe cosmology3,4, the dynamics of nuclear collision experiments described by quantum chromodynamics5,6, and the post-quench dynamics in dilute quantum gases in non-relativistic quantum field theory7-11. However, an experimental demonstration of such scaling evolution in space and time in a quantum many-body system has been lacking. Here we observe the emergence of universal dynamics by evaluating spatially resolved spin correlations in a quasi-one-dimensional spinor Bose-Einstein condensate12-16. For long evolution times we extract the scaling properties from the spatial correlations of the spin excitations. From this we find the dynamics to be governed by an emergent conserved quantity and the transport of spin excitations towards low momentum scales. Our results establish an important class of non-stationary systems whose dynamics is encoded in time-independent scaling exponents and functions, signalling the existence of non-thermal fixed points10,17,18. We confirm that the non-thermal scaling phenomenon involves no fine-tuning of parameters, by preparing different initial conditions and observing the same scaling behaviour. Our analogue quantum simulation approach provides the basis with which to reveal the underlying mechanisms and characteristics of non-thermal universality classes. One may use this universality to learn, from experiments with ultracold gases, about fundamental aspects of dynamics studied in cosmology and quantum chromodynamics.}, } @article {pmid30405225, year = {2018}, author = {Koss, MJ and Blecha, L and Bernhard, P and Hung, CL and Lu, JR and Trakthenbrot, B and Treister, E and Weigel, A and Sartori, LF and Mushotzky, R and Schawinski, K and Ricci, C and Veilleux, S and Sanders, DB}, title = {A population of luminous accreting black holes with hidden mergers.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {214-216}, doi = {10.1038/s41586-018-0652-7}, pmid = {30405225}, issn = {1476-4687}, support = {NNH16CT03C/NASA/NASA/United States ; }, abstract = {Major galaxy mergers are thought to play an important part in fuelling the growth of supermassive black holes1. However, observational support for this hypothesis is mixed, with some studies showing a correlation between merging galaxies and luminous quasars2,3 and others showing no such association4,5. Recent observations have shown that a black hole is likely to become heavily obscured behind merger-driven gas and dust, even in the early stages of the merger, when the galaxies are well separated6-8 (5 to 40 kiloparsecs). Merger simulations further suggest that such obscuration and black-hole accretion peaks in the final merger stage, when the two galactic nuclei are closely separated9 (less than 3 kiloparsecs). Resolving this final stage requires a combination of high-spatial-resolution infrared imaging and high-sensitivity hard-X-ray observations to detect highly obscured sources. However, large numbers of obscured luminous accreting supermassive black holes have been recently detected nearby (distances below 250 megaparsecs) in X-ray observations10. Here we report high-resolution infrared observations of hard-X-ray-selected black holes and the discovery of obscured nuclear mergers, the parent populations of supermassive-black-hole mergers. We find that obscured luminous black holes (bolometric luminosity higher than 2 × 1044 ergs per second) show a significant (P < 0.001) excess of late-stage nuclear mergers (17.6 per cent) compared to a sample of inactive galaxies with matching stellar masses and star formation rates (1.1 per cent), in agreement with theoretical predictions. Using hydrodynamic simulations, we confirm that the excess of nuclear mergers is indeed strongest for gas-rich major-merger hosts of obscured luminous black holes in this final stage.}, } @article {pmid30405223, year = {2018}, author = {Ngor, PB and Lek, S and McCann, KS and Hogan, ZS}, title = {Dams threaten world's largest inland fishery.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {184}, doi = {10.1038/d41586-018-07304-1}, pmid = {30405223}, issn = {1476-4687}, } @article {pmid30405222, year = {2018}, author = {Aldeen AlRyalat, S}, title = {Open data are a boon for underfunded researchers.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {184}, doi = {10.1038/d41586-018-07310-3}, pmid = {30405222}, issn = {1476-4687}, } @article {pmid30405221, year = {2018}, author = {Krummel, M}, title = {Nobel notes value of basic research for new drugs.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {184}, doi = {10.1038/d41586-018-07307-y}, pmid = {30405221}, issn = {1476-4687}, } @article {pmid30405220, year = {2018}, author = {Liao, SE}, title = {Mentorship training curbs academic abuse.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {184}, doi = {10.1038/d41586-018-07308-x}, pmid = {30405220}, issn = {1476-4687}, } @article {pmid30405219, year = {2018}, author = {Chen, J and Li, Z}, title = {Chinese pilot project tracks progress towards SDGs.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {184}, doi = {10.1038/d41586-018-07309-w}, pmid = {30405219}, issn = {1476-4687}, } @article {pmid30405217, year = {2018}, author = {Kolodrubetz, M}, title = {Quenching our thirst for universality.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {191-192}, doi = {10.1038/d41586-018-07272-6}, pmid = {30405217}, issn = {1476-4687}, } @article {pmid30405215, year = {2018}, author = {Dixon, KO and Das, M and Kuchroo, VK}, title = {Human disease mutations highlight the inhibitory function of TIM-3.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1640-1641}, doi = {10.1038/s41588-018-0289-3}, pmid = {30405215}, issn = {1546-1718}, } @article {pmid30404918, year = {2018}, author = {Liu, Y and Mondello, P and Erazo, T and Tannan, NB and Asgari, Z and de Stanchina, E and Nanjangud, G and Seshan, VE and Wang, S and Wendel, HG and Younes, A}, title = {NOXA genetic amplification or pharmacologic induction primes lymphoma cells to BCL2 inhibitor-induced cell death.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12034-12039}, pmid = {30404918}, issn = {1091-6490}, support = {P50 CA192937/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Apoptosis Regulatory Proteins/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Female ; Gene Amplification/drug effects ; Histone Deacetylase Inhibitors/pharmacology/therapeutic use ; Humans ; Lymphoma, Large B-Cell, Diffuse/*drug therapy/*genetics/metabolism/pathology ; Mice ; Mice, Nude ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Panobinostat/pharmacology ; Proto-Oncogene Proteins c-bcl-2/*antagonists & inhibitors/*genetics/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Although diffuse large B cell lymphoma (DLBCL) cells widely express the BCL2 protein, they rarely respond to treatment with BCL2-selective inhibitors. Here we show that DLBCL cells harboring PMAIP1/NOXA gene amplification were highly sensitive to BCL2 small-molecule inhibitors. In these cells, BCL2 inhibition induced cell death by activating caspase 9, which was further amplified by caspase-dependent cleavage and depletion of MCL1. In DLBCL cells lacking NOXA amplification, BCL2 inhibition was associated with an increase in MCL1 protein abundance in a BIM-dependent manner, causing a decreased antilymphoma efficacy. In these cells, dual inhibition of MCL1 and BCL2 was required for enhanced killing. Pharmacologic induction of NOXA, using the histone deacetylase inhibitor panobinostat, decreased MCL1 protein abundance and increased lymphoma cell vulnerability to BCL2 inhibitors in vitro and in vivo. Our data provide a mechanistic rationale for combination strategies to disrupt lymphoma cell codependency on BCL2 and MCL1 proteins in DLBCL.}, } @article {pmid30404917, year = {2018}, author = {Doupé, DP and Marshall, OJ and Dayton, H and Brand, AH and Perrimon, N}, title = {Drosophila intestinal stem and progenitor cells are major sources and regulators of homeostatic niche signals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12218-12223}, pmid = {30404917}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; P50 CA127003/CA/NCI NIH HHS/United States ; R01 GM084947/GM/NIGMS NIH HHS/United States ; BB/L00786X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 092545//Wellcome Trust/United Kingdom ; 092096//Wellcome Trust/United Kingdom ; C6946/A14492//Cancer Research UK/United Kingdom ; 103792//Wellcome Trust/United Kingdom ; }, abstract = {Epithelial homeostasis requires the precise balance of epithelial stem/progenitor proliferation and differentiation. While many signaling pathways that regulate epithelial stem cells have been identified, it is probable that other regulators remain unidentified. Here, we use gene-expression profiling by targeted DamID to identify the stem/progenitor-specific transcription and signaling factors in the Drosophila midgut. Many signaling pathway components, including ligands of most major pathways, exhibit stem/progenitor-specific expression and have regulatory regions bound by both intrinsic and extrinsic transcription factors. In addition to previously identified stem/progenitor-derived ligands, we show that both the insulin-like factor Ilp6 and TNF ligand eiger are specifically expressed in the stem/progenitors and regulate normal tissue homeostasis. We propose that intestinal stem cells not only integrate multiple signals but also contribute to and regulate the homeostatic signaling microenvironmental niche through the expression of autocrine and paracrine factors.}, } @article {pmid30404916, year = {2018}, author = {Yu, H and Dalby, PA}, title = {Coupled molecular dynamics mediate long- and short-range epistasis between mutations that affect stability and aggregation kinetics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11043-E11052}, pmid = {30404916}, issn = {1091-6490}, mesh = {Amino Acid Substitution/genetics ; Epistasis, Genetic/*genetics ; Escherichia coli/enzymology/*genetics ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Mutation/genetics ; Protein Engineering/*methods ; Protein Structure, Secondary/genetics ; Thermodynamics ; Transketolase/*genetics ; }, abstract = {Multiple mutations are typically required to significantly improve protein stability or aggregation kinetics. However, when several substitutions are made in a single protein, the mutations can potentially interact in a nonadditive manner, resulting in epistatic effects, which can hamper protein-engineering strategies to improve thermostability or aggregation kinetics. Here, we have examined the role of protein dynamics in mediating epistasis between pairs of mutations. With Escherichia coli transketolase (TK) as a model, we explored the epistatic interactions between two single variants H192P and A282P, and also between the double-mutant H192P/A282P and two single variants, I365L or G506A. Epistasis was determined for several measures of protein stability, including the following: the free-energy barrier to kinetic inactivation, ∆∆G‡; thermal transition midpoint temperatures, Tm; and aggregation onset temperatures, Tagg Nonadditive epistasis was observed between neighboring mutations as expected, but also for distant mutations located in the surface and core regions of different domains. Surprisingly, the epistatic behaviors for each measure of stability were often different for any given pairwise recombination, highlighting that kinetic and thermodynamic stabilities do not always depend on the same structural features. Molecular-dynamics simulations and a pairwise cross-correlation analysis revealed that mutations influence the dynamics of their local environment, but also in some cases the dynamics of regions distant in the structure. This effect was found to mediate epistatic interactions between distant mutations and could therefore be exploited in future protein-engineering strategies.}, } @article {pmid30404915, year = {2018}, author = {Gao, A and Shrinivas, K and Lepeudry, P and Suzuki, HI and Sharp, PA and Chakraborty, AK}, title = {Evolution of weak cooperative interactions for biological specificity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11053-E11060}, pmid = {30404915}, issn = {1091-6490}, support = {P01 CA042063/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Cell Physiological Phenomena ; *Computer Simulation ; Humans ; *Models, Biological ; Protein Domains/physiology ; Proteins/metabolism ; }, abstract = {A hallmark of biological systems is that particular functions and outcomes are realized in specific contexts, such as when particular signals are received. One mechanism for mediating specificity is described by Fisher's "lock and key" metaphor, exemplified by enzymes that bind selectively to a particular substrate via specific finely tuned interactions. Another mechanism, more prevalent in multicellular organisms, relies on multivalent weak cooperative interactions. Its importance has recently been illustrated by the recognition that liquid-liquid phase transitions underlie the formation of membraneless condensates that perform specific cellular functions. Based on computer simulations of an evolutionary model, we report that the latter mechanism likely became evolutionarily prominent when a large number of tasks had to be performed specifically for organisms to function properly. We find that the emergence of weak cooperative interactions for mediating specificity results in organisms that can evolve to accomplish new tasks with fewer, and likely less lethal, mutations. We argue that this makes the system more capable of undergoing evolutionary changes robustly, and thus this mechanism has been repeatedly positively selected in increasingly complex organisms. Specificity mediated by weak cooperative interactions results in some useful cross-reactivity for related tasks, but at the same time increases susceptibility to misregulation that might lead to pathologies.}, } @article {pmid30404914, year = {2018}, author = {Liu, H and Hofmann, J and Fish, I and Schaake, B and Eitel, K and Bartuschat, A and Kaindl, J and Rampp, H and Banerjee, A and Hübner, H and Clark, MJ and Vincent, SG and Fisher, JT and Heinrich, MR and Hirata, K and Liu, X and Sunahara, RK and Shoichet, BK and Kobilka, BK and Gmeiner, P}, title = {Structure-guided development of selective M3 muscarinic acetylcholine receptor antagonists.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12046-12050}, pmid = {30404914}, issn = {1091-6490}, support = {R35 GM122481/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetylcholine/metabolism ; Amino Acid Sequence ; Crystallography, X-Ray ; Drug Design ; Humans ; Molecular Docking Simulation/methods ; Muscarinic Antagonists/chemistry/metabolism ; Receptor, Muscarinic M2/antagonists & inhibitors/metabolism ; Receptor, Muscarinic M3/*antagonists & inhibitors/*genetics ; }, abstract = {Drugs that treat chronic obstructive pulmonary disease by antagonizing the M3 muscarinic acetylcholine receptor (M3R) have had a significant effect on health, but can suffer from their lack of selectivity against the M2R subtype, which modulates heart rate. Beginning with the crystal structures of M2R and M3R, we exploited a single amino acid difference in their orthosteric binding pockets using molecular docking and structure-based design. The resulting M3R antagonists had up to 100-fold selectivity over M2R in affinity and over 1,000-fold selectivity in vivo. The crystal structure of the M3R-selective antagonist in complex with M3R corresponded closely to the docking-predicted geometry, providing a template for further optimization.}, } @article {pmid30404913, year = {2018}, author = {Persi, E and Wolf, YI and Leiserson, MDM and Koonin, EV and Ruppin, E}, title = {Criticality in tumor evolution and clinical outcome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11101-E11110}, pmid = {30404913}, issn = {1091-6490}, mesh = {Humans ; Models, Genetic ; Mutation/*genetics ; *Mutation Accumulation ; Neoplasms/*genetics/mortality/pathology ; Proteome/*genetics ; Selection, Genetic/*genetics ; Treatment Outcome ; }, abstract = {How mutation and selection determine the fitness landscape of tumors and hence clinical outcome is an open fundamental question in cancer biology, crucial for the assessment of therapeutic strategies and resistance to treatment. Here we explore the mutation-selection phase diagram of 6,721 tumors representing 23 cancer types by quantifying the overall somatic point mutation load (ML) and selection (dN/dS) in the entire proteome of each tumor. We show that ML strongly correlates with patient survival, revealing two opposing regimes around a critical point. In low-ML cancers, a high number of mutations indicates poor prognosis, whereas high-ML cancers show the opposite trend, presumably due to mutational meltdown. Although the majority of cancers evolve near neutrality, deviations are observed at extreme MLs. Melanoma, with the highest ML, evolves under purifying selection, whereas in low-ML cancers, signatures of positive selection are observed, demonstrating how selection affects tumor fitness. Moreover, different cancers occupy specific positions on the ML-dN/dS plane, revealing a diversity of evolutionary trajectories. These results support and expand the theory of tumor evolution and its nonlinear effects on survival.}, } @article {pmid30404912, year = {2018}, author = {Kiaris, H and Chatzistamou, I}, title = {Inhibition of tumor growth by agonists of growth hormone-releasing hormone.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11876-11878}, pmid = {30404912}, issn = {1091-6490}, mesh = {*Gonadotropin-Releasing Hormone ; *Growth Hormone-Releasing Hormone ; Humans ; Neoplasms ; }, } @article {pmid30404911, year = {2018}, author = {Khan, Y and Han, D and Pierre, A and Ting, J and Wang, X and Lochner, CM and Bovo, G and Yaacobi-Gross, N and Newsome, C and Wilson, R and Arias, AC}, title = {A flexible organic reflectance oximeter array.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11015-E11024}, pmid = {30404911}, issn = {1091-6490}, mesh = {Adult ; Equipment Design ; Forearm/*blood supply ; Forehead/*blood supply ; Humans ; Ischemia/blood ; Models, Theoretical ; Oximetry/*instrumentation/*methods ; Oxygen/*blood ; Oxyhemoglobins/analysis/metabolism ; }, abstract = {Transmission-mode pulse oximetry, the optical method for determining oxygen saturation in blood, is limited to only tissues that can be transilluminated, such as the earlobes and the fingers. The existing sensor configuration provides only single-point measurements, lacking 2D oxygenation mapping capability. Here, we demonstrate a flexible and printed sensor array composed of organic light-emitting diodes and organic photodiodes, which senses reflected light from tissue to determine the oxygen saturation. We use the reflectance oximeter array beyond the conventional sensing locations. The sensor is implemented to measure oxygen saturation on the forehead with 1.1% mean error and to create 2D oxygenation maps of adult forearms under pressure-cuff-induced ischemia. In addition, we present mathematical models to determine oxygenation in the presence and absence of a pulsatile arterial blood signal. The mechanical flexibility, 2D oxygenation mapping capability, and the ability to place the sensor in various locations make the reflectance oximeter array promising for medical sensing applications such as monitoring of real-time chronic medical conditions as well as postsurgery recovery management of tissues, organs, and wounds.}, } @article {pmid30404910, year = {2018}, author = {Medeiros, LP and Garcia, G and Thompson, JN and Guimarães, PR}, title = {The geographic mosaic of coevolution in mutualistic networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12017-12022}, pmid = {30404910}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; Biological Coevolution/*genetics ; Biological Evolution ; Ecosystem ; Gene Flow/genetics ; Geography ; Models, Genetic ; Pollination ; Symbiosis ; }, abstract = {Ecological interactions shape adaptations through coevolution not only between pairs of species but also through entire multispecies assemblages. Local coevolution can then be further altered through spatial processes that have been formally partitioned in the geographic mosaic theory of coevolution. A major current challenge is to understand the spatial patterns of coadaptation that emerge across ecosystems through the interplay between gene flow and selection in networks of interacting species. Here, we combine a coevolutionary model, network theory, and empirical information on species interactions to investigate how gene flow and geographical variation in selection affect trait patterns in mutualistic networks. We show that gene flow has the surprising effect of favoring trait matching, especially among generalist species in species-rich networks typical of pollination and seed dispersal interactions. Using an analytical approximation of our model, we demonstrate that gene flow promotes trait matching by making the adaptive landscapes of different species more similar to each other. We use this result to show that the progressive loss of gene flow associated with habitat fragmentation may undermine coadaptation in mutualisms. Our results therefore provide predictions of how spatial processes shape the evolution of species-rich interactions and how the widespread fragmentation of natural landscapes may modify the coevolutionary process.}, } @article {pmid30404659, year = {2018}, author = {Green, SB and Markaki, A}, title = {Interprofessional palliative care education for pediatric oncology clinicians: an evidence-based practice review.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {797}, pmid = {30404659}, issn = {1756-0500}, abstract = {OBJECTIVE: Clinician education and expertise in palliative care varies widely across pediatric oncology programs. The purpose of this evidence-based practice review was to identify interprofessional palliative care education models applicable to pediatric oncology settings as well as methods for evaluating their impact on clinical practice.

RESULTS: Based on a literature search in PubMed, CINAHL and Embase, which identified 13 articles meeting inclusion/exclusion criteria, the following three themes emerged: (1) establishment of effective modalities and teaching strategies, (2) development of an interprofessional palliative care curriculum, and (3) program evaluation to assess impact on providers' self-perceived comfort in delivering palliative care and patient/family perceptions of care received. Remarkably, health professionals reported receiving limited palliative care training, with little evidence of systematic evaluation of practice changes following training completion. Improving palliative care delivery was linked to the development and integration of an interprofessional palliative care curriculum. Suggested evaluation strategies included: (1) eliciting patient and family feedback, (2) standardizing care delivery measures, and (3) evaluating outcomes of care.}, } @article {pmid30404617, year = {2018}, author = {Ross, KG and Shoemaker, D}, title = {Unexpected patterns of segregation distortion at a selfish supergene in the fire ant Solenopsis invicta.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {101}, pmid = {30404617}, issn = {1471-2156}, support = {1354479//National Science Foundation/ ; }, abstract = {BACKGROUND: The Sb supergene in the fire ant Solenopsis invicta determines the form of colony social organization, with colonies whose inhabitants bear the element containing multiple reproductive queens and colonies lacking it containing only a single queen. Several features of this supergene - including suppressed recombination, presence of deleterious mutations, association with a large centromere, and "green-beard" behavior - suggest that it may be a selfish genetic element that engages in transmission ratio distortion (TRD), defined as significant departures in progeny allele frequencies from Mendelian inheritance ratios. We tested this possibility by surveying segregation ratios in embryo progenies of 101 queens of the "polygyne" social form (3512 embryos) using three supergene-linked markers and twelve markers outside the supergene.

RESULTS: Significant departures from Mendelian ratios were observed at the supergene loci in 3-5 times more progenies than expected in the absence of TRD and than found, on average, among non-supergene loci. Also, supergene loci displayed the greatest mean deviations from Mendelian ratios among all study loci, although these typically were modest. A surprising feature of the observed inter-progeny variation in TRD was that significant deviations involved not only excesses of supergene alleles but also similarly frequent excesses of the alternate alleles on the homologous chromosome. As expected given the common occurrence of such "drive reversal" in this system, alleles associated with the supergene gain no consistent transmission advantage over their alternate alleles at the population level. Finally, we observed low levels of recombination and incomplete gametic disequilibrium across the supergene, including between adjacent markers within a single inversion.

CONCLUSIONS: Our data confirm the prediction that the Sb supergene is a selfish genetic element capable of biasing its own transmission during reproduction, yet counterselection for suppressor loci evidently has produced an evolutionary stalemate in TRD between the variant homologous haplotypes on the "social chromosome". Evidence implicates prezygotic segregation distortion as responsible for the TRD we document, with "true" meiotic drive the most likely mechanism. Low levels of recombination and incomplete gametic disequilibrium across the supergene suggest that selection does not preserve a single uniform supergene haplotype responsible for inducing polygyny.}, } @article {pmid30404613, year = {2018}, author = {Patrone, V and Minuti, A and Lizier, M and Miragoli, F and Lucchini, F and Trevisi, E and Rossi, F and Callegari, ML}, title = {Differential effects of coconut versus soy oil on gut microbiota composition and predicted metabolic function in adult mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {808}, pmid = {30404613}, issn = {1471-2164}, abstract = {BACKGROUND: Animal studies show that high fat (HF) diet-induced gut microbiota contributes to the development of obesity. Oil composition of high-fat diet affects metabolic inflammation differently with deleterious effects by saturated fat. The aim of the present study was to examine the diversity and metabolic capacity of the cecal bacterial community in C57BL/6 N mice administered two different diets, enriched respectively with coconut oil (HFC, high in saturated fat) or soy oil (HFS, high in polyunsaturated fat). The relative impact of each hypercaloric diet was evaluated after 2 and 8 weeks of feeding, and compared with that of a low-fat, control diet (LF).

RESULTS: The HFC diet induced the same body weight gain and fat storage as the HFS diet, but produced higher plasma cholesterol levels after 8 weeks of treatment. At the same time point, the cecal microbiota of HFC diet-fed mice was characterized by an increased relative abundance of Allobaculum, Anaerofustis, F16, Lactobacillus reuteri and Deltaproteobacteria, and a decreased relative abundance of Akkermansia muciniphila compared to HFS mice. Comparison of cecal microbiota of high-fat fed mice versus control mice indicated major changes that were shared between the HFC and the HFS diet, including the increase in Lactobacillus plantarum, Lutispora, and Syntrophomonas, while some other shifts were specifically associated to either coconut or soy oil. Prediction of bacterial gene functions showed that the cecal microbiota of HFC mice was depleted of pathways involved in fatty acid metabolism, amino acid metabolism, xenobiotic degradation and metabolism of terpenoids and polyketides compared to mice on HFS diet. Correlation analysis revealed remarkable relationships between compositional changes in the cecal microbiota and alterations in the metabolic and transcriptomic phenotypes of high-fat fed mice.

CONCLUSIONS: The study highlights significant differences in cecal microbiota composition and predictive functions of mice consuming a diet enriched in coconut vs soy oil. The correlations established between specific bacterial taxa and various traits linked to host lipid metabolism and energy storage give insights into the role and functioning of the gut microbiota that may contribute to diet-induced metabolic disorders.}, } @article {pmid30404611, year = {2018}, author = {Dimitrakopoulou, K and Wik, E and Akslen, LA and Jonassen, I}, title = {Deblender: a semi-/unsupervised multi-operational computational method for complete deconvolution of expression data from heterogeneous samples.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {408}, pmid = {30404611}, issn = {1471-2105}, support = {223250//Norges Forskningsråd/ ; }, mesh = {Algorithms ; Computational Biology/*methods ; Gene Expression/*genetics ; Humans ; }, abstract = {BACKGROUND: Towards discovering robust cancer biomarkers, it is imperative to unravel the cellular heterogeneity of patient samples and comprehend the interactions between cancer cells and the various cell types in the tumor microenvironment. The first generation of 'partial' computational deconvolution methods required prior information either on the cell/tissue type proportions or the cell/tissue type-specific expression signatures and the number of involved cell/tissue types. The second generation of 'complete' approaches allowed estimating both of the cell/tissue type proportions and cell/tissue type-specific expression profiles directly from the mixed gene expression data, based on known (or automatically identified) cell/tissue type-specific marker genes.

RESULTS: We present Deblender, a flexible complete deconvolution tool operating in semi-/unsupervised mode based on the user's access to known marker gene lists and information about cell/tissue composition. In case of no prior knowledge, global gene expression variability is used in clustering the mixed data to substitute marker sets with cluster sets. In addition, we integrate a model selection criterion to predict the number of constituent cell/tissue types. Moreover, we provide a tailored algorithmic scheme to estimate mixture proportions for realistic experimental cases where the number of involved cell/tissue types exceeds the number of mixed samples. We assess the performance of Deblender and a set of state-of-the-art existing tools on a comprehensive set of benchmark and patient cancer mixture expression datasets (including TCGA).

CONCLUSION: Our results corroborate that Deblender can be a valuable tool to improve understanding of gene expression datasets with implications for prediction and clinical utilization. Deblender is implemented in MATLAB and is available from (https://github.com/kondim1983/Deblender/).}, } @article {pmid30404610, year = {2018}, author = {Ning, L and Lin, Z and Gu, J and Gan, L and Li, Y and Wang, H and Miao, L and Zhang, L and Wang, B and Li, M}, title = {The initial deficiency of protein processing and flavonoids biosynthesis were the main mechanisms for the male sterility induced by SX-1 in Brassica napus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {806}, pmid = {30404610}, issn = {1471-2164}, support = {31471532//National Natural Science Foundation of China/ ; NCET110172//New Century Talents Support Program by the Ministry of Education of China/ ; }, abstract = {BACKGROUND: Rapeseed (Brassica napus) is an important oil seed crop in the Brassicaceae family. Chemical induced male sterility (CIMS) is one of the widely used method to produce the hybrids in B. napus. Identification of the key genes and pathways that involved in CIMS were important to understand the underlying molecular mechanism. In the present report, a multi-omics integrative analysis, including of the proteomic, transcriptomic and miRNAs, combined with morphological and physiological analysis were conducted.

RESULTS: Earlier degeneration of the tapetosomes and elaioplasts, aberrantly stacking in tapetal cells and incompletely deposition in tryphine of pollen wall were observed in chemical hybridization agent (CHA) of SX-1 treated B. napus through SEM and TEM analysis. It was revealed that the deficiencies in protein processing in endoplasmic reticulum (ER) and flavonoids biosynthesis were occurred at early stage in the SX-1 treated materials. Subsequently, plant hormone signal transduction, biosynthesis of amino acids, fatty acids and steroid in anther at later stages were identified down-regulated after SX-1 treatment. 144 transcript factors (TFs) were also indentified to down-regulated at early stage, which suggested the early regulation in anther and pollen wall development were disordered in CHA treated B. napus. In addition, 7 important miRNAs were identified and 2 of the predicted target genes of miRNAs were Rf-like genes.

CONCLUSIONS: Taken together, an interaction network of candidate genes and the putative metabolism pathways were constructed based on the multi-omics integrative analysis, it provided a new insight into the male sterility induced by CHA of SX-1 in B. napus.}, } @article {pmid30404602, year = {2018}, author = {Cheng, Q and Bai, S and Ge, G and Li, P and Liu, L and Zhang, C and Jia, Y}, title = {Study on differentially expressed genes related to defoliation traits in two alfalfa varieties based on RNA-Seq.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {807}, pmid = {30404602}, issn = {1471-2164}, support = {31572461//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Alfalfa (Medicago sativa) is a widely cultivated, essential commercial forage crop. The protein content in its leaves is the critical factor in determining the quality of alfalfa. Thus far, the understanding of the molecular mechanism of alfalfa defoliation traits remains unclear. The transcriptome database created by RNA-Seq is used to identify critical genes related to defoliation traits.

RESULTS: In this study, we sequenced the transcriptomes of the Zhungeer variety (with easy leaf abscission) and WL319HQ variety (without easy leaf abscission). Among the identified 66,734 unigenes, 706 differentially expressed genes (DEGs) upregulated, and 392 unigenes downregulated in the Zhungeer vs WL319HQ leaf. KEGG pathway annotations showed that 8,414 unigenes were annotated to 87 pathways and contained 281 DEGs. Six DEGs belonging to the "Carotenoid biosynthesis", "Plant hormone signal transduction" and "Circadian rhythm-plant" pathways involved in defoliation traits were identified and validated by RT-qPCR analyses.

CONCLUSIONS: This study used RNA-Seq to discover genes associated with defoliation traits between two alfalfa varieties. Our transcriptome data dramatically enriches alfalfa functional genomic studies. In addition, these data provide theoretical guidance for field production practice and genetic breeding, as well as references for future study of defoliation traits in alfalfa.}, } @article {pmid30404601, year = {2018}, author = {Hu, W and Hua, X and Zhang, Q and Wang, J and Shen, Q and Zhang, X and Wang, K and Yu, Q and Lin, YR and Ming, R and Zhang, J}, title = {New insights into the evolution and functional divergence of the SWEET family in Saccharum based on comparative genomics.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {270}, pmid = {30404601}, issn = {1471-2229}, support = {31201260//National Natural Science Foundation of China/ ; 2013AA102604//National High-tech R&D Program/ ; KLa17073A//Program for New Century Excellent Talents in Fujian Province/ ; 2016NZ0001//Science and Technology Major Project of Fujian Province/ ; }, mesh = {Gene Expression Regulation, Plant ; Genomics/methods ; Haplotypes/genetics ; Phylogeny ; Plant Proteins/genetics ; Saccharum/*genetics ; }, abstract = {BACKGROUND: The SWEET (Sugars Will Eventually be Exported Transporters) gene family is a recently identified group of sugar transporters that play an indispensable role in sugar efflux, phloem loading, plant-pathogen interaction, nectar secretion, and reproductive tissue development. However, little information on Saccharum SWEET is available for this crop with a complex genetic background.

RESULTS: In this study, 22 SWEET genes were identified from Saccharum spontaneum Bacterial Artificial Chromosome libraries sequences. Phylogenetic analyses of SWEETs from 11 representative plant species showed that gene expansions of the SWEET family were mainly caused by the recent gene duplication in dicot plants, while these gene expansions were attributed to the ancient whole genome duplication (WGD) in monocot plant species. Gene expression profiles were obtained from RNA-seq analysis. SWEET1a and SWEET2s had higher expression levels in the transitional zone and maturing zone than in the other analyzed zones. SWEET1b was mainly expressed in the leaf tissues and the mature zone of the leaf of both S. spontaneum and S. officinarum, and displayed a peak in the morning and was undetectable in both sclerenchyma and parenchyma cells from the mature stalks of S. officinarum. SsSWEET4a\4b had higher expression levels than SWEET4c and were mainly expressed in the stems of seedlings and mature plants. SWEET13s are recently duplicated genes, and the expression of SWEET13s dramatically increased from the maturing to mature zones. SWEET16b's expression was not detected in S. officinarum, but displayed a rhythmic diurnal expression pattern.

CONCLUSIONS: Our study revealed the gene evolutionary history of SWEETs in Saccharum and SWEET1b was found to be a sucrose starvation-induced gene involved in the sugar transportation in the high photosynthetic zones. SWEET13c was identified as the key player in the efflux of sugar transportation in mature photosynthetic tissues. SWEET4a\4b were found to be mainly involved in sugar transportation in the stalk. SWEET1a\2a\4a\4b\13a\16b were suggested to be the genes contributing to the differences in sugar contents between S. spontaneum and S. officinarum. Our results are valuable for further functional analysis of SWEET genes and utilization of the SWEET genes for genetic improvement of Saccharum for biofuel production.}, } @article {pmid30404596, year = {2018}, author = {Atanasova, L and Dubey, M and Grujić, M and Gudmundsson, M and Lorenz, C and Sandgren, M and Kubicek, CP and Jensen, DF and Karlsson, M}, title = {Evolution and functional characterization of pectate lyase PEL12, a member of a highly expanded Clonostachys rosea polysaccharide lyase 1 family.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {178}, pmid = {30404596}, issn = {1471-2180}, abstract = {BACKGROUND: Pectin is one of the major and most complex plant cell wall components that needs to be overcome by microorganisms as part of their strategies for plant invasion or nutrition. Microbial pectinolytic enzymes therefore play a significant role for plant-associated microorganisms and for the decomposition and recycling of plant organic matter. Recently, comparative studies revealed significant gene copy number expansion of the polysaccharide lyase 1 (PL1) pectin/pectate lyase gene family in the Clonostachys rosea genome, while only low numbers were found in Trichoderma species. Both of these fungal genera are widely known for their ability to parasitize and kill other fungi (mycoparasitism) and certain species are thus used for biocontrol of plant pathogenic fungi.

RESULTS: In order to understand the role of the high number of pectin degrading enzymes in Clonostachys, we studied diversity and evolution of the PL1 gene family in C. rosea compared with other Sordariomycetes with varying nutritional life styles. Out of 17 members of C. rosea PL1, we could only detect two to be secreted at acidic pH. One of them, the pectate lyase pel12 gene was found to be strongly induced by pectin and, to a lower degree, by polygalacturonic acid. Heterologous expression of the PEL12 in a PL1-free background of T. reesei revealed direct enzymatic involvement of this protein in utilization of pectin at pH 5 without a requirement for Ca2+. The mutants showed increased utilization of pectin compounds, but did not increase biocontrol ability in detached leaf assay against the plant pathogen Botrytis cinerea compared to the wild type.

CONCLUSIONS: In this study, we aimed to gain insight into diversity and evolution of the PL1 gene family in C. rosea and other Sordariomycete species in relation to their nutritional modes. We show that C. rosea PL1 expansion does not correlate with its mycoparasitic nutritional mode and resembles those of strong plant pathogenic fungi. We further investigated regulation, specificity and function of the C. rosea PEL12 and show that this enzyme is directly involved in degradation of pectin and pectin-related compounds, but not in C. rosea biocontrol.}, } @article {pmid30403586, year = {2018}, author = {Hu, Y and Wei, L and Feng, Y and Xie, Y and Zong, Z}, title = {Klebsiella huaxiensis sp. nov., recovered from human urine.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003102}, pmid = {30403586}, issn = {1466-5034}, abstract = {A strain of a member of the genus Klebsiella, WCHKl090001, was recovered from a human urine sample in PR China in 2017. Phylogenetic analysis based on gyrA and rpoB housekeeping genes revealed that the strain was distinct from any previously described species of the genus Klebsiella though it was clustered with the Klebsiella oxytoca phylogroup, including Klebsiella grimontii, Klebsiella michiganensis and Klebsiella oxytoca. The whole-genome sequence of strain WCHKl090001 has an up to 87.18 % average nucleotide identity with those of type strains of all known species of the genus Klebsiella. In silico DNA-DNA hybridization (isDDH) values between strain WCHKl090001 and type strains of all known species of the genus Klebsiella ranged from 22.3 to 35.2 %. Strain WCHKl090001 could be distinguished from species of the Klebsiella oxytocaphylogroup by its negative Voges-Proskauer reaction. Genotypic and phenotypic characteristics from this study indicate that strain WCHKl090001 should be considered to represent a novel species of the genus Klebsiella, for which the name Klebsiellahuaxiensis sp. nov. is proposed. The type strain is WCHKl090001T (=GDMCC 1.1379T=CNCTC 7650T).}, } @article {pmid30403585, year = {2018}, author = {Khan, IU and Habib, N and Asem, MD and Salam, N and Xiao, M and Zhou, EM and Zhi, XY and Li, WJ}, title = {Aquabacterium tepidiphilum sp. nov., a moderately thermophilic bacterium isolated from a hot spring.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003103}, pmid = {30403585}, issn = {1466-5034}, abstract = {A Gram-stain-negative, aerobic, non-spore-forming and rod-shaped bacterium, designated YIM 730274T, was isolated from a sediment sample collected from a hot spring located in Tibet, PR China, and was characterized by using a polyphasic taxonomy approach. Cells were motile by means of a polar flagellum. The strain was oxidase- and catalase-positive, and contained polyalkanoates and polyphosphate as storage polymers. Growth occurred at 25-50 °C, at pH 6.0-8.5 and with 0.5-1.0 % NaCl. The major fatty acids (>10 %) were summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The known polar lipids comprised of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and phosphatidylserine. The isoprenoid quinone was Q-8. The G+C content of genomic DNA was 70.7 mol%. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that the strain forms a monophyletic branch at the periphery of the evolutionary radiation occupied by the genus Aquabacterium in the class Betaproteobacteria. The most closely related phylogenetic neighbours were Aquabacterium limnoticumABP-4T (97.8 % 16S rRNA gene sequence identity) and Aquabacterium communeB8T (97.2 % 16SrRNA gene sequence identity). DNA-DNA relatedness values between YIM 730274T and A. limnoticum KCTC 23306T (46.4±0.4 %) and A. commune DSM 11901T (42.2±1.2 %) were well below the 70 % limit for species identification. YIM 730274T was distinguishable from other members of the genus Aquabacterium by the differences in phenotypic, chemotaxonomic and genotypic characteristics. YIM 730274T merits recognition as a representative of a novel species of the genus Aquabacterium. It is proposed that the isolate should be classified in the genus Aquabacterium as representing a novel species, Aquabacteriumtepidiphilum sp. nov. The type strain is YIM 730274T (=KCTC 52716T=CCTCC AB 2016295T).}, } @article {pmid30403584, year = {2019}, author = {Li, C and Shi, K and Zhang, Y and Wang, G}, title = {Nocardioides silvaticus sp. nov., isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {68-73}, doi = {10.1099/ijsem.0.003079}, pmid = {30403584}, issn = {1466-5034}, abstract = {A Gram-stain-positive, non-motile, rod-shaped bacterial strain S-34T was isolated from forest soil. According to 16S rRNA gene sequence analysis, strain S-34T was related to Nocardioides members and showed the highest similarities to Nocardioides thalensis NCCP-696T (97.3 %) and Nocardioides panacisoliGsoil 346T (97.0 %), Nocardioides litorisoli X-2T (96.5 %) and Nocardioides immobilis FLL521T (96.4 %). Phylogenetic trees showed that strain S-34T fell within the cluster containing strain S-34T and N. immobilis FLL521T. The levels of DNA-DNA relatedness between strain S-34T and N. thalensis CCTCC AB 2016296T and between strain S-34T and N. panacisoli KCTC 19470T were 50.6 and 58.8 %, respectively. The genome orthoANI value between strain S-34T and N. immobilis CCTCC AB 2017083T was 82.4 %. Strain S-34T had ll-diaminopimelic acid in the cell-wall peptidoglycan, diphosphatidylglycerol, phosphatidylglycerol, four unknown phospholipids and one unknown lipid as the polar lipids, meanquinone-8(H4) as the only respiratory quinone and iso-C16 : 0, C17:1ω8c, C17:1ω6c, C17 : 0 and C17 : 0 10-methyl (tbsa) as the major fatty acids. The genome length of strain S-34T was 4.53 Mb containing 52 contigs and with a DNA G+C content of 71.2 mol%. Strain S-34T could be distinguished from the other Nocardioides members mainly based on the data of phylogenetic analyses, DNA-DNA hybridization, polar lipids and some biochemical differences. Therefore, strain S-34T represents a novel species of the genus Nocardioides, for which the name Nocardioidessilvaticus sp. nov. is proposed. The type strain is S-34T (=KCTC 49137T=CCTCC AB 2018079T).}, } @article {pmid30403583, year = {2019}, author = {Li, Y and Zheng, MH and Wang, HM and Lin, CL and Wang, XZ}, title = {Brenneria corticis sp. nov., isolated from symptomatic bark of Populus×euramericana canker.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {69}, number = {1}, pages = {63-67}, doi = {10.1099/ijsem.0.003077}, pmid = {30403583}, issn = {1466-5034}, abstract = {A Gram-stain-negative, facultatively anaerobic, motile bacterial strain, designated gBX10-1-2T, was isolated from symptomatic bark of Populus×euramericana canker in China. Phylogenetic analysis based on its 16S rRNA gene sequence showed that the novel isolate belonged to the genus Brenneria, and shared the highest sequence similarity to Brenneria nigrifluens LMG 2694T (98.3 %). In the phylogenetic trees based on the four housekeeping genes sequences, the novel strain formed a separate branch different from B. nigrifluens LMG 2694T, indicating that the novel strain should be classified as a novel species. The genome sequence-derived average nucleotide identity (ANI) values between the novel isolate and B. nigrifluens LMG 2694T, Brenneria roseaesubsp. roseae FRB 222T and Brenneria roseaesubsp. americana FRB 223T were less than 85 %, lower than the proposed species boundary ANI cut-off value (95-96 %). The DNA G+C content was 56.2 mol%, and the main fatty acids were C16 : 0, C16 : 1ω7c, C18 : 1ω7c and C17 : 0cyclo. Based on the phenotypic and genotypic characteristics, strain gBX10-1-2T represents a novel species of genus Brenneria, for which the name Brenneria corticis sp. nov. is proposed. The type strain is gBX10-1-2T (=CFCC 11842T=KCTC 42840T).}, } @article {pmid30401984, year = {2018}, author = {O'Connor, LJ and Price, AL}, title = {Author Correction: Distinguishing genetic correlation from causation across 52 diseases and complex traits.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1753}, doi = {10.1038/s41588-018-0296-4}, pmid = {30401984}, issn = {1546-1718}, abstract = {In the version of this article originally published, there were errors in equations. In the HTML and PDF, the initial term of equation 10 was estimated GCP but should have been estimated standard error, while a 'hat' was missing from the first alpha in the second term of the expression at the end of the paragraph following equation (6) in the Methods. In addition, in the abstract in the PDF, a subscript 1 was used instead of a subscript 2 for the final term of the first fourth-moment expression. These errors have been corrected in the HTML, PDF and print versions of the paper.}, } @article {pmid30401860, year = {2018}, author = {}, title = {Why the Bank of England should put a female scientist on its next £50 note.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {156}, doi = {10.1038/d41586-018-07324-x}, pmid = {30401860}, issn = {1476-4687}, mesh = {*Banking, Personal ; *Research Personnel ; *Science ; Sex Factors ; United Kingdom ; Workforce ; }, } @article {pmid30401859, year = {2018}, author = {}, title = {Life on Earth to have its DNA analysed in the name of conservation.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {155-156}, doi = {10.1038/d41586-018-07323-y}, pmid = {30401859}, issn = {1476-4687}, mesh = {Animals ; *Biodiversity ; Conservation of Natural Resources/*methods ; Extinction, Biological ; Genome/*genetics ; Genomics/*trends ; }, } @article {pmid30401858, year = {2018}, author = {Figgener, C}, title = {What I learnt pulling a straw out of a turtle's nose.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {157}, doi = {10.1038/d41586-018-07287-z}, pmid = {30401858}, issn = {1476-4687}, mesh = {Animals ; Ecology/*methods ; Nose ; *Public Opinion ; Research Personnel/education/*psychology ; *Social Change ; Social Media/*statistics & numerical data ; *Turtles/anatomy & histology ; Video Recording ; Water Pollution/*prevention & control ; }, } @article {pmid30401857, year = {2018}, author = {Bhadelia, N}, title = {Lessons from the Ebola front lines.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {180-181}, doi = {10.1038/d41586-018-07294-0}, pmid = {30401857}, issn = {1476-4687}, } @article {pmid30401856, year = {2018}, author = {Botham, CM and Evans, TM}, title = {How to design a winning fellowship proposal.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {283}, doi = {10.1038/d41586-018-07297-x}, pmid = {30401856}, issn = {1476-4687}, } @article {pmid30401855, year = {2018}, author = {Fletcher, D}, title = {Which biological systems should be engineered?.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {177-179}, doi = {10.1038/d41586-018-07291-3}, pmid = {30401855}, issn = {1476-4687}, } @article {pmid30401854, year = {2018}, author = {Good, M and Trepat, X}, title = {Cell parts to complex processes, from the bottom up.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {188-189}, doi = {10.1038/d41586-018-07246-8}, pmid = {30401854}, issn = {1476-4687}, } @article {pmid30401853, year = {2018}, author = {}, title = {Swarm of microscopic corkscrews speeds through the eyeball.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {159}, doi = {10.1038/d41586-018-07278-0}, pmid = {30401853}, issn = {1476-4687}, mesh = {*Vitreous Body ; }, } @article {pmid30401852, year = {2018}, author = {Morton, A}, title = {Coral scientists decry loss of funding for leading Australian reef institute.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {165}, doi = {10.1038/d41586-018-07270-8}, pmid = {30401852}, issn = {1476-4687}, mesh = {Animals ; *Anthozoa ; Australia ; Climate Change ; Coral Reefs ; Ecosystem ; *Global Warming ; }, } @article {pmid30401851, year = {2018}, author = {Marris, E}, title = {US Supreme Court allows historic kids' climate lawsuit to go forward.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {163-164}, doi = {10.1038/d41586-018-07214-2}, pmid = {30401851}, issn = {1476-4687}, mesh = {Adolescent ; Age Factors ; Child ; *Federal Government ; Global Warming/*legislation & jurisprudence/*prevention & control ; Human Activities ; Human Rights/*legislation & jurisprudence ; Humans ; *Liability, Legal ; *Supreme Court Decisions ; United States ; Young Adult ; }, } @article {pmid30401850, year = {2018}, author = {Witze, A}, title = {Argentina's mega-storms attract army of meteorologists.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {166}, doi = {10.1038/d41586-018-07268-2}, pmid = {30401850}, issn = {1476-4687}, } @article {pmid30401849, year = {2018}, author = {}, title = {Dark space cloud caught donning halo of hydrogen molecules.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {158}, doi = {10.1038/d41586-018-07280-6}, pmid = {30401849}, issn = {1476-4687}, } @article {pmid30401848, year = {2018}, author = {Wild, S}, title = {South Africa's invasive species guzzle precious water and cost US$450 million a year.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {164-165}, doi = {10.1038/d41586-018-07286-0}, pmid = {30401848}, issn = {1476-4687}, } @article {pmid30401847, year = {2018}, author = {Castelvecchi, D}, title = {Holy Cow! Astronomers agog at mysterious new supernova.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {168-169}, doi = {10.1038/d41586-018-07260-w}, pmid = {30401847}, issn = {1476-4687}, } @article {pmid30401846, year = {2018}, author = {}, title = {Humans indulged a taste for chocolate a millennium earlier than realized.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {158}, doi = {10.1038/d41586-018-07226-y}, pmid = {30401846}, issn = {1476-4687}, mesh = {*Cacao ; *Chocolate ; Domestication ; Food Preferences ; Humans ; Taste ; }, } @article {pmid30401845, year = {2018}, author = {}, title = {Randy pandas utter come-hither bleats.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {159}, doi = {10.1038/d41586-018-07219-x}, pmid = {30401845}, issn = {1476-4687}, mesh = {Animals ; Female ; Male ; *Sexual Behavior, Animal ; Ursidae/*physiology ; Vocalization, Animal/*physiology ; }, } @article {pmid30401844, year = {2018}, author = {}, title = {Life in a distant land triggers upheaval in immigrants' microbiomes.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {158}, doi = {10.1038/d41586-018-07223-1}, pmid = {30401844}, issn = {1476-4687}, mesh = {Emigrants and Immigrants ; *Emigration and Immigration ; *Gastrointestinal Microbiome ; Humans ; Microbiota ; }, } @article {pmid30401843, year = {2018}, author = {Maxmen, A}, title = {Machine learning spots natural selection at work in human genome.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {167}, doi = {10.1038/d41586-018-07225-z}, pmid = {30401843}, issn = {1476-4687}, } @article {pmid30401842, year = {2018}, author = {Witze, A}, title = {Embattled Thirty Meter Telescope scores big win in Hawaii's highest court.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {168}, doi = {10.1038/d41586-018-04444-2}, pmid = {30401842}, issn = {1476-4687}, } @article {pmid30401841, year = {2018}, author = {}, title = {A once-lush country on the verge of total deforestation.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {159}, doi = {10.1038/d41586-018-07230-2}, pmid = {30401841}, issn = {1476-4687}, mesh = {Biodiversity ; *Conservation of Natural Resources ; *Forests ; Haiti ; Trees ; }, } @article {pmid30401840, year = {2018}, author = {}, title = {Slot machine jingles encourage gamblers to raise the stakes.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {159}, doi = {10.1038/d41586-018-07224-0}, pmid = {30401840}, issn = {1476-4687}, mesh = {Choice Behavior ; *Cues ; *Gambling ; Humans ; Risk ; }, } @article {pmid30401839, year = {2018}, author = {Polovinkin, L and Hassaine, G and Perot, J and Neumann, E and Jensen, AA and Lefebvre, SN and Corringer, PJ and Neyton, J and Chipot, C and Dehez, F and Schoehn, G and Nury, H}, title = {Conformational transitions of the serotonin 5-HT3 receptor.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {275-279}, doi = {10.1038/s41586-018-0672-3}, pmid = {30401839}, issn = {1476-4687}, abstract = {The serotonin 5-HT3 receptor is a pentameric ligand-gated ion channel (pLGIC). It belongs to a large family of receptors that function as allosteric signal transducers across the plasma membrane1,2; upon binding of neurotransmitter molecules to extracellular sites, the receptors undergo complex conformational transitions that result in transient opening of a pore permeable to ions. 5-HT3 receptors are therapeutic targets for emesis and nausea, irritable bowel syndrome and depression3. In spite of several reported pLGIC structures4-8, no clear unifying view has emerged on the conformational transitions involved in channel gating. Here we report four cryo-electron microscopy structures of the full-length mouse 5-HT3 receptor in complex with the anti-emetic drug tropisetron, with serotonin, and with serotonin and a positive allosteric modulator, at resolutions ranging from 3.2 Å to 4.5 Å. The tropisetron-bound structure resembles those obtained with an inhibitory nanobody5 or without ligand9. The other structures include an 'open' state and two ligand-bound states. We present computational insights into the dynamics of the structures, their pore hydration and free-energy profiles, and characterize movements at the gate level and cation accessibility in the pore. Together, these data deepen our understanding of the gating mechanism of pLGICs and capture ligand binding in unprecedented detail.}, } @article {pmid30401838, year = {2018}, author = {Chang, L and Azzolin, L and Di Biagio, D and Zanconato, F and Battilana, G and Lucon Xiccato, R and Aragona, M and Giulitti, S and Panciera, T and Gandin, A and Sigismondo, G and Krijgsveld, J and Fassan, M and Brusatin, G and Cordenonsi, M and Piccolo, S}, title = {The SWI/SNF complex is a mechanoregulated inhibitor of YAP and TAZ.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {265-269}, doi = {10.1038/s41586-018-0658-1}, pmid = {30401838}, issn = {1476-4687}, abstract = {Inactivation of ARID1A and other components of the nuclear SWI/SNF protein complex occurs at very high frequencies in a variety of human malignancies, suggesting a widespread role for the SWI/SNF complex in tumour suppression1. However, the underlying mechanisms remain poorly understood. Here we show that ARID1A-containing SWI/SNF complex (ARID1A-SWI/SNF) operates as an inhibitor of the pro-oncogenic transcriptional coactivators YAP and TAZ2. Using a combination of gain- and loss-of-function approaches in several cellular contexts, we show that YAP/TAZ are necessary to induce the effects of the inactivation of the SWI/SNF complex, such as cell proliferation, acquisition of stem cell-like traits and liver tumorigenesis. We found that YAP/TAZ form a complex with SWI/SNF; this interaction is mediated by ARID1A and is alternative to the association of YAP/TAZ with the DNA-binding platform TEAD. Cellular mechanotransduction regulates the association between ARID1A-SWI/SNF and YAP/TAZ. The inhibitory interaction of ARID1A-SWI/SNF and YAP/TAZ is predominant in cells that experience low mechanical signalling, in which loss of ARID1A rescues the association between YAP/TAZ and TEAD. At high mechanical stress, nuclear F-actin binds to ARID1A-SWI/SNF, thereby preventing the formation of the ARID1A-SWI/SNF-YAP/TAZ complex, in favour of an association between TEAD and YAP/TAZ. We propose that a dual requirement must be met to fully enable the YAP/TAZ responses: promotion of nuclear accumulation of YAP/TAZ, for example, by loss of Hippo signalling, and inhibition of ARID1A-SWI/SNF, which can occur either through genetic inactivation or because of increased cell mechanics. This study offers a molecular framework in which mechanical signals that emerge at the tissue level together with genetic lesions activate YAP/TAZ to induce cell plasticity and tumorigenesis.}, } @article {pmid30401837, year = {2018}, author = {Basak, S and Gicheru, Y and Rao, S and Sansom, MSP and Chakrapani, S}, title = {Cryo-EM reveals two distinct serotonin-bound conformations of full-length 5-HT3A receptor.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {270-274}, pmid = {30401837}, issn = {1476-4687}, support = {P30 EY011373/EY/NEI NIH HHS/United States ; R01 GM108921/GM/NIGMS NIH HHS/United States ; }, abstract = {The 5-HT3A serotonin receptor1, a cationic pentameric ligand-gated ion channel (pLGIC), is the clinical target for management of nausea and vomiting associated with radiation and chemotherapies2. Upon binding, serotonin induces a global conformational change that encompasses the ligand-binding extracellular domain (ECD), the transmembrane domain (TMD) and the intracellular domain (ICD), the molecular details of which are unclear. Here we present two serotonin-bound structures of the full-length 5-HT3A receptor in distinct conformations at 3.32 Å and 3.89 Å resolution that reveal the mechanism underlying channel activation. In comparison to the apo 5-HT3A receptor, serotonin-bound states underwent a large twisting motion in the ECD and TMD, leading to the opening of a 165 Å permeation pathway. Notably, this motion results in the creation of lateral portals for ion permeation at the interface of the TMD and ICD. Combined with molecular dynamics simulations, these structures provide novel insights into conformational coupling across domains and functional modulation.}, } @article {pmid30401836, year = {2018}, author = {Latorre, E and Kale, S and Casares, L and Gómez-González, M and Uroz, M and Valon, L and Nair, RV and Garreta, E and Montserrat, N and Del Campo, A and Ladoux, B and Arroyo, M and Trepat, X}, title = {Active superelasticity in three-dimensional epithelia of controlled shape.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {203-208}, doi = {10.1038/s41586-018-0671-4}, pmid = {30401836}, issn = {1476-4687}, abstract = {Fundamental biological processes are carried out by curved epithelial sheets that enclose a pressurized lumen. How these sheets develop and withstand three-dimensional deformations has remained unclear. Here we combine measurements of epithelial tension and shape with theoretical modelling to show that epithelial sheets are active superelastic materials. We produce arrays of epithelial domes with controlled geometry. Quantification of luminal pressure and epithelial tension reveals a tensional plateau over several-fold areal strains. These extreme strains in the tissue are accommodated by highly heterogeneous strains at a cellular level, in seeming contradiction to the measured tensional uniformity. This phenomenon is reminiscent of superelasticity, a behaviour that is generally attributed to microscopic material instabilities in metal alloys. We show that in epithelial cells this instability is triggered by a stretch-induced dilution of the actin cortex, and is rescued by the intermediate filament network. Our study reveals a type of mechanical behaviour-which we term active superelasticity-that enables epithelial sheets to sustain extreme stretching under constant tension.}, } @article {pmid30401835, year = {2018}, author = {Shi, H and Zhang, X and Weng, YL and Lu, Z and Liu, Y and Lu, Z and Li, J and Hao, P and Zhang, Y and Zhang, F and Wu, Y and Delgado, JY and Su, Y and Patel, MJ and Cao, X and Shen, B and Huang, X and Ming, GL and Zhuang, X and Song, H and He, C and Zhou, T}, title = {m6A facilitates hippocampus-dependent learning and memory through YTHDF1.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {249-253}, pmid = {30401835}, issn = {1476-4687}, support = {P01 NS097206/NS/NINDS NIH HHS/United States ; R35 NS097370/NS/NINDS NIH HHS/United States ; RM1 HG008935/HG/NHGRI NIH HHS/United States ; R37 NS047344/NS/NINDS NIH HHS/United States ; R56 NS047344/NS/NINDS NIH HHS/United States ; R01 NS047344/NS/NINDS NIH HHS/United States ; R01 DA043361/DA/NIDA NIH HHS/United States ; R01 GM113194/GM/NIGMS NIH HHS/United States ; R21 NS103159/NS/NINDS NIH HHS/United States ; R01 MH105128/MH/NIMH NIH HHS/United States ; }, abstract = {N6-methyladenosine (m6A), the most prevalent internal RNA modification on mammalian messenger RNAs, regulates the fates and functions of modified transcripts through m6A-specific binding proteins1-5. In the nervous system, m6A is abundant and modulates various neural functions6-11. Whereas m6A marks groups of mRNAs for coordinated degradation in various physiological processes12-15, the relevance of m6A for mRNA translation in vivo remains largely unknown. Here we show that, through its binding protein YTHDF1, m6A promotes protein translation of target transcripts in response to neuronal stimuli in the adult mouse hippocampus, thereby facilitating learning and memory. Mice with genetic deletion of Ythdf1 show learning and memory defects as well as impaired hippocampal synaptic transmission and long-term potentiation. Re-expression of YTHDF1 in the hippocampus of adult Ythdf1-knockout mice rescues the behavioural and synaptic defects, whereas hippocampus-specific acute knockdown of Ythdf1 or Mettl3, which encodes the catalytic component of the m6A methyltransferase complex, recapitulates the hippocampal deficiency. Transcriptome-wide mapping of YTHDF1-binding sites and m6A sites on hippocampal mRNAs identified key neuronal genes. Nascent protein labelling and tether reporter assays in hippocampal neurons showed that YTHDF1 enhances protein synthesis in a neuronal-stimulus-dependent manner. In summary, YTHDF1 facilitates translation of m6A-methylated neuronal mRNAs in response to neuronal stimulation, and this process contributes to learning and memory.}, } @article {pmid30401834, year = {2018}, author = {Mizuhashi, K and Ono, W and Matsushita, Y and Sakagami, N and Takahashi, A and Saunders, TL and Nagasawa, T and Kronenberg, HM and Ono, N}, title = {Resting zone of the growth plate houses a unique class of skeletal stem cells.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {254-258}, pmid = {30401834}, issn = {1476-4687}, support = {P01 DK011794/DK/NIDDK NIH HHS/United States ; R00 DE022564/DE/NIDCR NIH HHS/United States ; R01 DE026666/DE/NIDCR NIH HHS/United States ; R03 DE027421/DE/NIDCR NIH HHS/United States ; }, abstract = {Skeletal stem cells regulate bone growth and homeostasis by generating diverse cell types, including chondrocytes, osteoblasts and marrow stromal cells. The emerging concept postulates that there exists a distinct type of skeletal stem cell that is closely associated with the growth plate1-4, which is a type of cartilaginous tissue that has critical roles in bone elongation5. The resting zone maintains the growth plate by expressing parathyroid hormone-related protein (PTHrP), which interacts with Indian hedgehog (Ihh) that is released from the hypertrophic zone6-10, and provides a source of other chondrocytes11. However, the identity of skeletal stem cells and how they are maintained in the growth plate are unknown. Here we show, in a mouse model, that skeletal stem cells are formed among PTHrP-positive chondrocytes within the resting zone of the postnatal growth plate. PTHrP-positive chondrocytes expressed a panel of markers for skeletal stem and progenitor cells, and uniquely possessed the properties of skeletal stem cells in cultured conditions. Cell-lineage analysis revealed that PTHrP-positive chondrocytes in the resting zone continued to form columnar chondrocytes in the long term; these chondrocytes underwent hypertrophy, and became osteoblasts and marrow stromal cells beneath the growth plate. Transit-amplifying chondrocytes in the proliferating zone-which was concertedly maintained by a forward signal from undifferentiated cells (PTHrP) and a reverse signal from hypertrophic cells (Ihh)-provided instructive cues to maintain the cell fates of PTHrP-positive chondrocytes in the resting zone. Our findings unravel a type of somatic stem cell that is initially unipotent and acquires multipotency at the post-mitotic stage, underscoring the malleable nature of the skeletal cell lineage. This system provides a model in which functionally dedicated stem cells and their niches are specified postnatally, and maintained throughout tissue growth by a tight feedback regulation system.}, } @article {pmid30401810, year = {2018}, author = {Lai, B and Gao, W and Cui, K and Xie, W and Tang, Q and Jin, W and Hu, G and Ni, B and Zhao, K}, title = {Publisher Correction: Principles of nucleosome organization revealed by single-cell micrococcal nuclease sequencing.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {E17}, doi = {10.1038/s41586-018-0690-1}, pmid = {30401810}, issn = {1476-4687}, abstract = {Change history: In Fig. 1c of this Letter, the two graphs were duplicates. The right panel of Fig. 1c has been corrected online.}, } @article {pmid30401758, year = {2018}, author = {Mann, A}, title = {Inner Workings: Hunting for microbial life throughout the solar system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11348-11350}, pmid = {30401758}, issn = {1091-6490}, } @article {pmid30401743, year = {2018}, author = {Engelhardt, SC and Kingma, SA and Taborsky, M}, title = {No evidence for a heritable altruism polymorphism in Tibetan ground tits.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11208-E11209}, pmid = {30401743}, issn = {1091-6490}, mesh = {*Altruism ; Gene Frequency ; *Polymorphism, Genetic ; Tibet ; }, } @article {pmid30401742, year = {2018}, author = {Wang, C and Lu, X}, title = {Reply to Engelhardt et al.: Inclusive fitness does maintain a heritable altruism polymorphism in Tibetan ground tits.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11210-E11211}, pmid = {30401742}, issn = {1091-6490}, mesh = {*Altruism ; Game Theory ; *Genetic Fitness ; Tibet ; }, } @article {pmid30401741, year = {2018}, author = {Rogers, RD and Gurau, G}, title = {Is "choline and geranate" an ionic liquid or deep eutectic solvent system?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E10999}, pmid = {30401741}, issn = {1091-6490}, mesh = {*Choline ; Insulin ; *Ionic Liquids ; Pharmaceutical Preparations ; Solvents ; }, } @article {pmid30401740, year = {2018}, author = {Banerjee, A and Ibsen, K and Brown, T and Chen, R and Agatemor, C and Mitragotri, S}, title = {Reply to Rogers and Gurau: Definitions of ionic liquids and deep eutectic solvents.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11000-E11001}, pmid = {30401740}, issn = {1091-6490}, mesh = {Insulin ; *Ionic Liquids ; *Solvents ; }, } @article {pmid30401739, year = {2018}, author = {Zhou, H and Helliker, BR and Huber, M and Dicks, A and Akçay, E}, title = {C4 photosynthesis and climate through the lens of optimality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12057-12062}, pmid = {30401739}, issn = {1091-6490}, mesh = {Biological Evolution ; Carbon/metabolism ; Carbon Cycle ; Carbon Dioxide/analysis ; Climate ; Computer Simulation ; Models, Biological ; Nitrogen/metabolism ; Paleontology/*methods ; Photosynthesis/genetics/*physiology ; Plant Leaves/chemistry ; Plant Transpiration/physiology ; Water ; }, abstract = {CO2, temperature, water availability, and light intensity were all potential selective pressures that determined the competitive advantage and expansion of the C4 photosynthetic carbon-concentrating mechanism over the last ∼30 My. To tease apart how selective pressures varied along the ecological trajectory of C4 expansion and dominance, we coupled hydraulics to photosynthesis models while optimizing photosynthesis over stomatal resistance and leaf/fine-root allocation. We further examined the importance of nitrogen reallocation from the dark to the light reactions. We show here that the primary selective pressures favoring C4 dominance changed through the course of C4 evolution. The higher stomatal resistance and leaf-to-root ratios enabled by C4 led to an advantage without any initial difference in hydraulic properties. We further predict a reorganization of the hydraulic system leading to higher turgor-loss points and possibly lower hydraulic conductance. Selection on nitrogen reallocation varied with CO2 concentration. Through paleoclimate model simulations, we find that water limitation was the primary driver for a C4 advantage, with atmospheric CO2 as high as 600 ppm, thus confirming molecular-based estimates for C4 evolution in the Oligocene. Under these high-CO2 conditions, nitrogen reallocation was necessary. Low CO2 and high light, but not nitrogen reallocation, were the primary drivers for the mid- to late-Miocene global expansion of C4 We also predicted the timing and spatial distribution for origins of C4 ecological dominance. The predicted origins are broadly consistent with prior estimates, but expand upon them to include a center of origin in northwest Africa and a Miocene-long origin in Australia.}, } @article {pmid30401738, year = {2018}, author = {Fernandez, RF and Kim, SQ and Zhao, Y and Foguth, RM and Weera, MM and Counihan, JL and Nomura, DK and Chester, JA and Cannon, JR and Ellis, JM}, title = {Acyl-CoA synthetase 6 enriches the neuroprotective omega-3 fatty acid DHA in the brain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12525-12530}, doi = {10.1073/pnas.1807958115}, pmid = {30401738}, issn = {1091-6490}, abstract = {Docosahexaenoic acid (DHA) is an omega-3 fatty acid that is highly abundant in the brain and confers protection against numerous neurological diseases, yet the fundamental mechanisms regulating the enrichment of DHA in the brain remain unknown. Here, we have discovered that a member of the long-chain acyl-CoA synthetase family, Acsl6, is required for the enrichment of DHA in the brain by generating an Acsl6-deficient mouse (Acsl6-/-). Acsl6 is highly enriched in the brain and lipid profiling of Acsl6-/- tissues reveals consistent reductions in DHA-containing lipids in tissues highly abundant with Acsl6. Acsl6-/- mice demonstrate motor impairments, altered glutamate metabolism, and increased astrogliosis and microglia activation. In response to a neuroinflammatory lipopolysaccharide injection, Acsl6-/- brains show similar increases in molecular and pathological indices of astrogliosis compared with controls. These data demonstrate that Acsl6 is a key mediator of neuroprotective DHA enrichment in the brain.}, } @article {pmid30401737, year = {2018}, author = {Gold-Parker, A and Gehring, PM and Skelton, JM and Smith, IC and Parshall, D and Frost, JM and Karunadasa, HI and Walsh, A and Toney, MF}, title = {Acoustic phonon lifetimes limit thermal transport in methylammonium lead iodide.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11905-11910}, pmid = {30401737}, issn = {1091-6490}, abstract = {Hybrid organic-inorganic perovskites (HOIPs) have become an important class of semiconductors for solar cells and other optoelectronic applications. Electron-phonon coupling plays a critical role in all optoelectronic devices, and although the lattice dynamics and phonon frequencies of HOIPs have been well studied, little attention has been given to phonon lifetimes. We report high-precision momentum-resolved measurements of acoustic phonon lifetimes in the hybrid perovskite methylammonium lead iodide (MAPI), using inelastic neutron spectroscopy to provide high-energy resolution and fully deuterated single crystals to reduce incoherent scattering from hydrogen. Our measurements reveal extremely short lifetimes on the order of picoseconds, corresponding to nanometer mean free paths and demonstrating that acoustic phonons are unable to dissipate heat efficiently. Lattice-dynamics calculations using ab initio third-order perturbation theory indicate that the short lifetimes stem from strong three-phonon interactions and a high density of low-energy optical phonon modes related to the degrees of freedom of the organic cation. Such short lifetimes have significant implications for electron-phonon coupling in MAPI and other HOIPs, with direct impacts on optoelectronic devices both in the cooling of hot carriers and in the transport and recombination of band edge carriers. These findings illustrate a fundamental difference between HOIPs and conventional photovoltaic semiconductors and demonstrate the importance of understanding lattice dynamics in the effort to develop metal halide perovskite optoelectronic devices.}, } @article {pmid30401736, year = {2018}, author = {Yeom, KH and Mitchell, S and Linares, AJ and Zheng, S and Lin, CH and Wang, XJ and Hoffmann, A and Black, DL}, title = {Polypyrimidine tract-binding protein blocks miRNA-124 biogenesis to enforce its neuronal-specific expression in the mouse.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11061-E11070}, pmid = {30401736}, issn = {1091-6490}, support = {R00 MH096807/MH/NIMH NIH HHS/United States ; R01 MH116220/MH/NIMH NIH HHS/United States ; U01 HG007912/HG/NHGRI NIH HHS/United States ; R01 GM049662/GM/NIGMS NIH HHS/United States ; T32 NS048004/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Embryonic Stem Cells/metabolism ; Gene Expression Regulation/*genetics ; Gene Knockout Techniques ; Heterogeneous-Nuclear Ribonucleoproteins/*metabolism ; Mice ; MicroRNAs/*biosynthesis/*genetics ; Models, Theoretical ; Neuroblastoma/metabolism ; Neurogenesis/genetics ; Neurons/*cytology ; Polypyrimidine Tract-Binding Protein/*metabolism ; RNA Processing, Post-Transcriptional/genetics ; Ribonuclease III/metabolism ; }, abstract = {MicroRNA (miRNA)-124 is expressed in neurons, where it represses genes inhibitory for neuronal differentiation, including the RNA binding protein PTBP1. PTBP1 maintains nonneuronal splicing patterns of mRNAs that switch to neuronal isoforms upon neuronal differentiation. We find that primary (pri)-miR-124-1 is expressed in mouse embryonic stem cells where mature miR-124 is absent. PTBP1 binds to this precursor RNA upstream of the miRNA stem-loop to inhibit mature miR-124 expression in vivo and DROSHA cleavage of pri-miR-124-1 in vitro. This function for PTBP1 in repressing miR-124 biogenesis defines an additional regulatory loop in the already intricate interplay between these two molecules. Applying mathematical modeling to examine the dynamics of this regulation, we find that the pool of pri-miR-124 whose maturation is blocked by PTBP1 creates a robust and self-reinforcing transition in gene expression as PTBP1 is depleted during early neuronal differentiation. While interlocking regulatory loops are often found between miRNAs and transcriptional regulators, our results indicate that miRNA targeting of posttranscriptional regulators also reinforces developmental decisions. Notably, induction of neuronal differentiation observed upon PTBP1 knockdown likely results from direct derepression of miR-124, in addition to indirect effects previously described.}, } @article {pmid30400996, year = {2018}, author = {Mujuni, F and Andrew, V and Mngumi, EB and Chibwe, E and Mshana, SE and Mirambo, MM}, title = {Predominance of Brucella abortus antibodies among women with spontaneous abortion in the city of Mwanza: unrecognized link or coincidence?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {792}, pmid = {30400996}, issn = {1756-0500}, abstract = {OBJECTIVE: This study investigated the association of Brucella seropositivity and spontaneous abortions in human population in the city of Mwanza, Tanzania.

RESULTS: A comparative cross sectional study which used 148 sera from women with spontaneous abortion and 250 sera from full-term delivered women was conducted in July 2017. Detection of Brucella abortus and Brucella melitensis antibodies was done using slide agglutination test. Data were analyzed using STATA version 13 software. The median age of the study participants was 25 (interquartile range 21-30) years. The overall seropositivity of Brucella antibodies was significantly higher among sera from women with spontaneous abortion than full term delivered women; (86/148, 58.1%: 95% CI 50-66 vs. 65/250, 26%: 95% CI 18-33, P < 0.001). Seropositivity of B. abortus was significantly higher among sera from women with spontaneous abortion than full-term delivered women (31.8% vs. 10.8%, P < 0.001). Women with abortion had 3.59 odds of being brucella seropositive compared to full term women (OR: 3.59, 95% CI; 2.25-5.74, P < 0.001). Seropositivity of Brucella antibodies is significantly higher among women with spontaneous abortion than full-term delivered women necessitating a need to investigate the relationship between Brucellosis and adverse pregnancy outcomes.}, } @article {pmid30400994, year = {2018}, author = {Zarova, C and Chiwaridzo, M and Tadyanemhandu, C and Machando, D and Dambi, JM}, title = {The impact of social support on the health-related quality of life of adult patients with tuberculosis in Harare, Zimbabwe: a cross-sectional survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {795}, pmid = {30400994}, issn = {1756-0500}, abstract = {OBJECTIVE: Tuberculosis (TB) is the second prime cause of mortality in Sub-Saharan Africa and remains a major worldwide public health problem. Unfortunately, patients with TB are at risk of poor mental health. However, patients who receive an adequate amount of social support are likely to have improved health outcomes. The study was done to establish how social support influences the health-related quality of life (HRQoL) of patients with TB in Harare, Zimbabwe. Data were collected from 332 TB patients and were analysed through structural equation modelling.

RESULTS: The mean age of the participants was 40.1 (SD 12.5) years and most were; males (53%), married (57.8%), educated (97.3%), unemployed (40.7%), stayed with family (74.4%), and reported of less than average levels of income (51.5%). Patients received the most significant amount of social support from the family. Patients also presented with lower HRQoL as they considerably reported of pain, anxiety and depression. The final model accounted for 68.8% of the variance. Despite methodological limitations, the study findings suggest that social support optimises patients' HRQoL. Based on the patients' responses, it was noted that patients presented with lower mental health, therefore, there is a need to develop and implement patient wellness interventions.}, } @article {pmid30400980, year = {2018}, author = {Ferede, ZT and Tullu, KD and Derese, SG and Yeshanew, AG}, title = {Prevalence and antimicrobial susceptibility pattern of Enterococcus species isolated from different clinical samples at Black Lion Specialized Teaching Hospital, Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {793}, pmid = {30400980}, issn = {1756-0500}, support = {1//Addis Ababa University/ ; }, abstract = {OBJECTIVE: Enterococci which are parts of the normal intestinal flora are opportunistic human pathogens. Their increasing importance is largely due to their resistance to antimicrobials. So the aim this study was to determine the prevalence and antimicrobial pattern of Enterococcus spp.

RESULT: From the total of 422 samples processed, 15 Enterococcus species were isolated. In this study, linezolid were the drug of choice for Enterococcus species, which showed 100% sensitive followed by vancomycin 93.3% sensitive. In contrast, highly resistance (80%) was observed for ampicillin followed by doxycycline (73.3%). All of isolated Enterococci were sensitive to linezolid, however, resistance was observed to common antibiotics. The presence of multidrug resistant Enterococci in our study should be considered as an alarm for Enterococcal infections.}, } @article {pmid30400979, year = {2018}, author = {Regina Pedrosa Soares, C and de Lira, CR and Cunha, MAH and Romão de Souza Junior, V and Lopes de Melo, F and de Araújo, PSR and Maciel, MAV}, title = {Prevalence of nasal colonization by methicillin-resistant Staphylococcus aureus in outpatients living with HIV/AIDS in a Referential Hospital of the Northeast of Brazil.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {794}, pmid = {30400979}, issn = {1756-0500}, abstract = {OBJECTIVE: The purpose of this study is to investigate the prevalence of MRSA among people living with HIV/AIDS (PLHA) being monitored in a tertiary outpatient hospital in the state of Pernambuco, in the Brazilian Northeast.

RESULTS: Staphylococcus aureus was isolated from a nasal swab and found in 31.4% of the individuals (95% CI 27.3-35.5), of whom 4.4% (95% CI 8.5-19.5) were MRSA, as confirmed by the presence of the mecA gene. For individuals whose S. aureus was recovered, the mean age was 41.5 years; 93.6% were on antiretroviral treatment. This group had CD4 cell counts > 200 (92%) and viral load ≤ 100 copies (79.1%). Use of antimicrobial agents in the past 12 months was found among 21% of the individuals, and 24.2% reported use of illicit drugs at lease once in their lifetime. Prevalence of nasal colonization by MSSA (26.7%) and MRSA (4.4%) was higher in comparison to other studies of this population; nevertheless, we were unable to establish factors associated with risk.}, } @article {pmid30400961, year = {2018}, author = {Mayala, HA and Bakari, KH and Mkangala, A and Magesa, M and Mghanga, FP and ZhaoHui, W}, title = {The association of 18F-FDG PET/CT and biomarkers in confirming coronary microvascular dysfunction.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {796}, pmid = {30400961}, issn = {1756-0500}, abstract = {OBJECTIVE: The purpose of this study is to evaluate the association between PET/CT CFR and biomarkers combined in confirming the diagnosis of coronary microvascular dysfunction.

RESULTS: A total of 28 patients (21 males and 7 females) were included in this descriptive observational study (both qualitative and quantitative). The mean patient age was 55.50 ± 10.21 years (range 27-70 years) and the median was 56.5 years (range 49-63 years). All patients underwent Echo, CAG and PET/CT scan. Chest tightness was the most common symptom in our study. Most patients had normal blood pressure (n = 18, 64.3%) while only (n = 10, 37.5%) had hypertension, and (n = 1, 3.6%) had diabetes mellitus. The mean HDL in CMVD (n = 25) and non-CMVD (n = 3) were 1.30 ± 0.39 and 1.08 ± 0.95, respectively, indicating that the difference between the groups was statistically significant (p = 0.04). Similarly, the mean HBA1c- (glycated haemoglobin) in CMVD (n = 25) and non-CMVD (n = 3) were 5.6 ± 0.53 and 5.0 ± 0.26, respectively, with (p = 0.03). Our findings managed to show the association between biomarkers and PET/CT CFR in confirming the diagnosis of coronary microvascular dysfunction.}, } @article {pmid30400929, year = {2018}, author = {Oduor, CO and Karanja, NK and Onwonga, RN and Mureithi, SM and Pelster, D and Nyberg, G}, title = {Enhancing soil organic carbon, particulate organic carbon and microbial biomass in semi-arid rangeland using pasture enclosures.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {45}, pmid = {30400929}, issn = {1472-6785}, abstract = {BACKGROUND: Rehabilitation of degraded rangelands through the establishment of enclosures (fencing grazing lands) is believed to improve soil quality and livelihoods, and enhance the sustainability of rangelands. Grazing dominated enclosure (GDE) and contractual grazing enclosure (CGE) are the common enclosure management systems in West Pokot County, Kenya. Under CGE, a farmer owning few animals leases the enclosure to households with relatively more livestock, while GDE is where the livestock utilizing the enclosure are purely owned by the farmer. Livestock management in both systems is via the free-range system. This study evaluated the effect of enclosure management on total soil organic carbon (SOC), particulate organic carbon (POC) and microbial biomass carbon (MBC) and nitrogen (MBN) as key indicators of soil degradation at 0-40 cm depth. The two enclosure systems were selected based on three age classes (3-10, 11-20 and > 20 years since establishment) (n = 3). The adjacent open grazing area (OGR) was used as a reference (n = 9).

RESULTS: Relative to OGR, the pasture enclosures significantly decreased soil bulk density and increased the concentrations of total organic C, POC, MBC and MBN compared to the degraded OGR (P < 0.001). Significantly higher concentrations of POC and MBC was recorded in GDE than CGE (P = 0.01). The POC accounted for 24.5-29.5% of the total SOC. MBC concentrations ranged from 32.05 ± 7.25 to 96.63 ± 5.31 µg C g-1 of soil in all grazing systems, and was positively correlated with total SOC and POC (P < 0.001). The proportional increase in POC and MBC was higher in GDE (56.6 and 30.5% respectively) compared to CGE (39.2 and 13.9% for POC and MBC respectively).

CONCLUSIONS: This study demonstrated that controlling livestock grazing through the establishment of pasture enclosures is the key strategy to enhance total SOC, POC, MBC, and MBN in degraded rangelands; a precondition for improving soil quality. Therefore, the establishment of enclosures is an effective restoration approach to restore degraded soils in semi-arid rangelands.}, } @article {pmid30400870, year = {2018}, author = {Ting, JJ and Cutter, AD}, title = {Demographic consequences of reproductive interference in multi-species communities.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {46}, pmid = {30400870}, issn = {1472-6785}, abstract = {BACKGROUND: Reproductive interference can mediate interference competition between species through sexual interactions that reduce the fitness of one species by another. Theory shows that the positive frequency-dependent effects of such costly errors in mate recognition can dictate species coexistence or exclusion even with countervailing resource competition differences between species. While usually framed in terms of pre-mating or post-zygotic costs, reproductive interference manifests between individual Caenorhabditis nematodes from negative interspecies gametic interactions: sperm cells from interspecies matings can migrate ectopically to induce female sterility and premature death. The potential for reproductive interference to exert population level effects on Caenorhabditis trait evolution and community structure, however, remains unknown.

RESULTS: Here we test whether a species that is superior in individual-level reproductive interference (C. nigoni) can exact negative demographic effects on competitor species that are superior in resource competition (C. briggsae and C. elegans). We observe coexistence over six generations and find evidence of demographic reproductive interference even under conditions unfavorable to its influence. C. briggsae and C. elegans show distinct patterns of reproductive interference in competitive interactions with C. nigoni.

CONCLUSIONS: These results affirm that individual level negative effects of reproductive interference mediated by gamete interactions can ramify to population demography, with the potential to influence patterns of species coexistence separately from the effects of direct resource competition.}, } @article {pmid30400867, year = {2018}, author = {Lai, YS and Shen, D and Zhang, W and Zhang, X and Qiu, Y and Wang, H and Dou, X and Li, S and Wu, Y and Song, J and Ji, G and Li, X}, title = {Temperature and photoperiod changes affect cucumber sex expression by different epigenetic regulations.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {268}, pmid = {30400867}, issn = {1471-2229}, support = {31171961//National Natural Science Foundation of China/ ; }, mesh = {Cucumis sativus/*genetics/physiology ; DNA Methylation/genetics ; Epigenesis, Genetic/*genetics ; Gene Expression Regulation, Plant/genetics ; Photoperiod ; Plant Proteins/genetics ; Temperature ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Cucumbers (Cucumis sativus) are known for their plasticity in sex expression. DNA methylation status determines gene activity but is susceptible to environmental condition changes. Thus, DNA methylation-based epigenetic regulation may at least partially account for the instability of cucumber sex expression. Do temperature and photoperiod that are the two most important environmental factors have equal effect on cucumber sex expression by similar epigenetic regulation mechanism? To answer this question, we did a two-factor experiment of temperature and photoperiod and generated methylome and transcriptome data from cucumber shoot apices.

RESULTS: The seasonal change in the femaleness of a cucumber core germplasm collection was investigated over five consecutive years. As a result, 71.3% of the 359 cucumber accessions significantly decreased their femaleness in early autumn when compared with spring. High temperature and long-day photoperiod treatments, which mimic early autumn conditions, are both unfavorable for female flower formation, and temperature is the predominant factor. High temperatures and long-day treatments both predominantly resulted in hypermethylation compared to demethylation, and temperature effect was decisive. The targeted cytosines shared in high-temperature and long-day photoperiod treatment showed the same change in DNA methylation level. Moreover, differentially expressed TEs (DETs) and the predicted epiregulation sites were clustered across chromosomes, and importantly, these sites were reproducible among different treatments. Essentially, the photoperiod treatment preferentially and significantly influenced flower development processes, while temperature treatment produced stronger responses from phytohormone-pathway-related genes. Cucumber AGAMOUS was likely epicontrolled exclusively by photoperiod while CAULIFLOWER A and CsACO3 were likely epicontrolled by both photoperiod and temperature.

CONCLUSIONS: Seasonal change of sex expression is a germplasm-wide phenomenon in cucumbers. High temperature and long-day photoperiod might have the same effect on the methylome via the same mechanism of gene-TE interaction but resulted in different epicontrol sites that account for different mechanisms between temperature- and photoperiod-dependent sex expression changes.}, } @article {pmid30400866, year = {2018}, author = {Yakir, E and Zhangjun, F and Sela, N and Xu, Y and Singh, V and Dagar, A and Joshi, JR and Müller, M and Munné-Bosch, S and Giovannoni, JJ and Vrebalov, J and Friedman, H}, title = {MaMADS2 repression in banana fruits modifies hormone synthesis and signalling pathways prior to climacteric stage.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {267}, pmid = {30400866}, issn = {1471-2229}, support = {OS-1322714 (NSF BSF 2012837) and IOS-1539831//National Science Foundation/ ; IS-4371-10C//United States - Israel Binational Agricultural Research and Development Fund/ ; }, mesh = {Cyclopentanes/metabolism ; Fruit/*metabolism ; Gene Expression Regulation, Plant/physiology ; Gibberellins/metabolism ; Musa/*metabolism ; Oxylipins/metabolism ; Plant Growth Regulators/metabolism ; Plant Proteins/*metabolism ; Salicylic Acid/metabolism ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: While the role of ethylene in fruit ripening has been widely studied, the contributions of additional plant hormones are less clear. Here we examined the interactions between the transcription factor MaMADS2-box which plays a major role in banana fruit ripening and hormonal regulation. Specifically, we used MaMADS2 repressed lines in transcriptome and hormonal analyses throughout ripening and assessed hormone and gene expression perturbations as compared to wild-type (WT) control fruit.

RESULTS: Our analyses revealed major differences in hormones levels and in expression of hormone synthesis and signaling genes mediated by MaMADS2 especially in preclimacteric pulp. Genes encoding ethylene biosynthesis enzymes had lower expression in the pulp of the repressed lines, consistent with reduced ethylene production. Generally, the expression of other hormone (auxin, gibberellins, abscisic acid, jasmonic acid and salicylic acid) response pathway genes were down regulated in the WT pulp prior to ripening, but remained high in MaMADS2 repressed lines. Hormone levels of abscisic acid were also higher, however, active gibberellin levels were lower and auxin levels were similar with MaMADS2 repression as compared to WT. Although abscisic level was higher in MaMADS2 repression, exogenous abscisic acid shortened the time to ethylene production and increased MaMADS2 mRNA accumulation in WT. Exogenous ethylene did not influence abscisic acid level. CRE - a cytokinin receptor, increased its expression during maturation in WT and was lower especially at prebreaker in the repressed line and zeatin level was lower at mature green of the repressed line in comparison to WT.

CONCLUSIONS: In addition to previously reported effects of MaMADS2 on ethylene, this transcription factor also influences other plant hormones, particularly at the pre-climacteric stage. The cytokinin pathway may play a previously unanticipated role via MaMADS2 in banana ripening. Finally, abscisic acid enhances MaMADS2 expression to promote ripening, but the transcription factor in turn auto inhibits ABA synthesis and signaling. Together, these results demonstrate a complex interaction of plant hormones and banana fruit ripening mediated by MaMADS2.}, } @article {pmid30400863, year = {2018}, author = {Zhu, J and Wang, X and Xu, Q and Zhao, S and Tai, Y and Wei, C}, title = {Global dissection of alternative splicing uncovers transcriptional diversity in tissues and associates with the flavonoid pathway in tea plant (Camellia sinensis).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {266}, pmid = {30400863}, issn = {1471-2229}, support = {31171608//National Natural Science Foundation of China/ ; 15czs08032//Special Innovative Province Construction in Anhui Province/ ; 2016080503B024//Special Project for Central Guiding Science and Technology Innovatio of Region in Anhui Province/ ; IRT1101//Programme for Changjiang Scholars and Innovative Research Team in University/ ; }, mesh = {Alternative Splicing/genetics/*physiology ; Camellia sinensis/genetics/*metabolism ; Catechin/metabolism ; Flavonoids/*metabolism ; Flowers/genetics/metabolism ; Gene Expression Regulation, Plant/genetics/physiology ; Plant Leaves/genetics/*metabolism ; Plant Proteins/*genetics/metabolism ; Transcription Factors/*genetics/metabolism ; }, abstract = {BACKGROUND: Alternative splicing (AS) regulates mRNA at the post-transcriptional level to change gene function in organisms. However, little is known about the AS and its roles in tea plant (Camellia sinensis), widely cultivated for making a popular beverage tea.

RESULTS: In our study, the AS landscape and dynamics were characterized in eight tissues (bud, young leaf, summer mature leaf, winter old leaf, stem, root, flower, fruit) of tea plant by Illumina RNA-Seq and confirmed by Iso-Seq. The most abundant AS (~ 20%) was intron retention and involved in RNA processes. The some alternative splicings were found to be tissue specific in stem and root etc. Thirteen co-expressed modules of AS transcripts were identified, which revealed a similar pattern between the bud and young leaves as well as a distinct pattern between seasons. AS events of structural genes including anthocyanidin reductase and MYB transcription factors were involved in biosynthesis of flavonoid, especially in vegetative tissues. The AS isoforms rather than the full-length ones were the major transcripts involved in flavonoid synthesis pathway, and is positively correlated with the catechins content conferring the tea taste. We propose that the AS is an important functional mechanism in regulating flavonoid metabolites.

CONCLUSION: Our study provides the insight into the AS events underlying tea plant's uniquely different developmental process and highlights the important contribution and efficacy of alternative splicing regulatory function to biosynthesis of flavonoids.}, } @article {pmid30400862, year = {2018}, author = {Hu, C and Yang, H and Jiang, K and Wang, L and Yang, B and Hsieh, T and Lan, S and Huang, W}, title = {Development of polymorphic microsatellite markers by using de novo transcriptome assembly of Calanthe masuca and C. sinica (Orchidaceae).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {800}, pmid = {30400862}, issn = {1471-2164}, support = {SAJC201607//The Sino-Africa Joint Center research project/ ; G152431//Shanghai Municipal Administration of Forestation and City Appearances/ ; 2013TW2SA0003//Chinese Academy of Sciences/ ; 2015TW1SA0001//Chinese Academy of Sciences/ ; G182418//Shanghai Municipal Adminastration of Forestation and City Appearances(CN)/ ; }, abstract = {BACKGROUND: Calanthe masuca and C. sinica are two genetically closely related species in Orchidaceae. C. masuca is widely distributed in Asia, whereas C. sinica is restricted to Yunnan and Guangxi Provinces in southwest China. Both play important roles in horticulture and are under the pressure of population decline. Understanding their genetic background can greatly help us develop effective conservation strategies for these species. Simple sequence repeats (SSRs) are useful for genetic diversity analysis, presumably providing key information for the study and preservation of the wild populations of the two species we are interested in.

RESULTS: In this study, we performed RNA-seq analysis on the leaves of C. masuca and C. sinica, obtaining 40,916 and 71,618 unigenes for each species, respectively. In total, 2,019/3,865 primer pairs were successfully designed from 3,764/7,189 putative SSRs, among which 197 polymorphic SSRs were screened out according to orthologous gene pairs. After mononucleotide exclusion, a subset of 129 SSR primers were analysed, and 13 of them were found to have high polymorphism levels. Further analysis demonstrated that they were feasible and effective against C. masuca and C. sinica as well as transferable to another species in Calanthe. Molecular evolutionary analysis revealed functional pathways commonly enriched in unigenes with similar evolutionary rates in the two species, as well as pathways specific to each species, implicating species-specific adaptation. The divergence time between the two closely related species was tentatively determined to be 3.42 ± 1.86 Mya.

CONCLUSIONS: We completed and analysed the transcriptomes of C. masuca and C. sinica, assembling large numbers of unigenes and generating effective polymorphic SSR markers. This is the first report of the development of expressed sequence tag (EST)-SSR markers for Calanthe. In addition, our study could enable further genetic diversity analysis and functional and comparative genomic studies on Calanthe.}, } @article {pmid30400857, year = {2018}, author = {Yu, F and Huang, Y and Luo, L and Li, X and Wu, J and Chen, R and Zhang, M and Deng, Z}, title = {An improved suppression subtractive hybridization technique to develop species-specific repetitive sequences from Erianthus arundinaceus (Saccharum complex).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {269}, pmid = {30400857}, issn = {1471-2229}, support = {31571730//National Natural Science Foundation of China/ ; 31401440//National Natural Science Foundation of China/ ; 31771863//National Natural Science Foundation of China/ ; CARS-170106//Modern Agriculture Technology of China/ ; 2015A030310286//Natural Science Foundation of Guangdong Province of China/ ; }, mesh = {Hybridization, Genetic ; In Situ Hybridization, Fluorescence ; Saccharum/*genetics ; Subtractive Hybridization Techniques/*methods ; }, abstract = {BACKGROUND: Sugarcane has recently attracted increased attention for its potential as a source of bioethanol and methane. However, a narrow genetic base has limited germplasm enhancement of sugarcane. Erianthus arundinaceus is an important wild genetic resource that has many excellent traits for improving cultivated sugarcane via wide hybridization. Species-specific repetitive sequences are useful for identifying genome components and investigating chromosome inheritance in noblization between sugarcane and E. arundinaceus. Here, suppression subtractive hybridization (SSH) targeting E. arundinaceus-specific repetitive sequences was performed. The five critical components of the SSH reaction system, including enzyme digestion of genomic DNA (gDNA), adapters, digested gDNA concentrations, primer concentrations, and LA Taq polymerase concentrations, were improved using a stepwise optimization method to establish a SSH system suitable for obtaining E. arundinaceus-specific gDNA fragments.

RESULTS: Specificity of up to 85.42% was confirmed for the SSH method as measured by reverse dot blot (RDB) of an E. arundinaceus subtractive library. Furthermore, various repetitive sequences were obtained from the E. arundinaceus subtractive library via fluorescence in situ hybridization (FISH), including subtelomeric and centromeric regions. EaCEN2-166F/R and EaSUB1-127F/R primers were then designed as species-specific markers to accurately validate E. arundinaceus authenticity.

CONCLUSIONS: This is the first report that E. arundinaceus-specific repetitive sequences were obtained via an improved SSH method. These results suggested that this novel SSH system could facilitate screening of species-specific repetitive sequences for species identification and provide a basis for development of similar applications for other plant species.}, } @article {pmid30400856, year = {2018}, author = {Engqvist, MKM}, title = {Correlating enzyme annotations with a large set of microbial growth temperatures reveals metabolic adaptations to growth at diverse temperatures.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {177}, pmid = {30400856}, issn = {1471-2180}, abstract = {BACKGROUND: The ambient temperature of all habitats is a key physical property that shapes the biology of microbes inhabiting them. The optimal growth temperature (OGT) of a microbe, is therefore a key piece of data needed to understand evolutionary adaptations manifested in their genome sequence. Unfortunately there is no growth temperature database or easily downloadable dataset encompassing the majority of cultured microorganisms. We are thus limited in interpreting genomic data to identify temperature adaptations in microbes.

RESULTS: In this work I significantly contribute to closing this gap by mining data from major culture collection centres to obtain growth temperature data for a nonredundant set of 21,498 microbes. The dataset (https://doi.org/10.5281/zenodo.1175608) contains mainly bacteria and archaea and spans psychrophiles, mesophiles, thermophiles and hyperthermophiles. Using this data a full 43% of all protein entries in the UniProt database can be annotated with the growth temperature of the species from which they originate. I validate the dataset by showing a Pearson correlation of up to 0.89 between growth temperature and mean enzyme optima, a physiological property directly influenced by the growth temperature. Using the temperature dataset I correlate the genomic occurance of enzyme functional annotations with growth temperature. I identify 319 enzyme functions that either increase or decrease in occurrence with temperature. Eight metabolic pathways were statistically enriched for these enzyme functions. Furthermore, I establish a correlation between 33 domains of unknown function (DUFs) with growth temperature in microbes, four of which (DUF438, DUF1524, DUF1957 and DUF3458_C) were significant in both archaea and bacteria.

CONCLUSIONS: The growth temperature dataset enables large-scale correlation analysis with enzyme function- and domain-level annotations. Growth-temperature dependent changes in their occurrence highlight potential evolutionary adaptations. A few of the identified changes are previously known, such as the preference for menaquinone biosynthesis through the futalosine pathway in bacteria growing at high temperatures. Others represent important starting points for future studies, such as DUFs where their occurrence change with temperature. The growth temperature dataset should become a valuable community resource and will find additional, important, uses in correlating genomic, transcriptomic, proteomic, metabolomic, phenotypic or taxonomic properties with temperature in future studies.}, } @article {pmid30400854, year = {2018}, author = {Jin, SW and Rahim, MA and Afrin, KS and Park, JI and Kang, JG and Nou, IS}, title = {Transcriptome profiling of two contrasting ornamental cabbage (Brassica oleracea var. acephala) lines provides insights into purple and white inner leaf pigmentation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {797}, pmid = {30400854}, issn = {1471-2164}, support = {Grant no. 213007-05-2-CG100//The Golden Seed Project (Center for Horticultural Seed Development, Ministry of Agriculture, Food and Rural affairs in the Republic of Korea (MAFRA))/ ; }, abstract = {BACKGROUND: Ornamental cabbage (Brassica oleracea var. acephala) is an attractive landscape plant that remains colorful at low temperatures during winter. Its key feature is its inner leaf coloration, which can include red, pink, lavender, blue, violet and white. Some ornamental cabbages exhibit variation in leaf color pattern linked to leaf developmental stage. However, little is known about the molecular mechanism underlying changes in leaf pigmentation pattern between developmental stages.

RESULTS: The transcriptomes of six ornamental cabbage leaf samples were obtained using Illumina sequencing technology. A total of 339.75 million high-quality clean reads were assembled into 46,744 transcripts and 46,744 unigenes. Furthermore, 12,771 genes differentially expressed across the different lines and stages were identified by pairwise comparison. We identified 74 and 13 unigenes as differentially expressed genes related to the anthocyanin biosynthetic pathway and chlorophyll metabolism, respectively. Among them, three unigenes (BoC4H2, BoUGT9, and BoGST21) and six unigenes (BoHEMA1, BoCRD1, BoPORC1, BoPORC2, BoCAO, and BoCLH1) were found as candidates for the genes encoding enzymes in the anthocyanin biosynthetic pathway and chlorophyll metabolism, respectively. In addition, two unigenes (BoRAX3 and BoTRB1) as MYB candidates, two unigenes (BoMUTE1, and BHLH168-like) as bHLH candidates were identified for purple pigmentation in ornamental cabbage.

CONCLUSION: Our results indicate that the purple inner leaves of purple ornamental cabbage result from a high level of anthocyanin biosynthesis, a high level of chlorophyll degradation and an extremely low level of chlorophyll biosynthesis, whereas the bicolor (purple/green) outer leaves are due to a moderate level of anthocyanin biosynthesis, a high level of chlorophyll degradation and a very low level of chlorophyll biosynthesis. In white ornamental cabbage, the white inner leaves are due to an extremely low level or absence of anthocyanin biosynthesis, a high level of chlorophyll degradation and a very low level of chlorophyll biosynthesis, whereas the bicolor (white/green) leaves are due to a high level of chlorophyll degradation and a low level of chlorophyll biosynthesis and absence of anthocyanin biosynthesis. These results provide insight into the molecular mechanisms underlying inner and bicolor leaf pigmentation in ornamental cabbage and offer a platform for assessing related ornamental species.}, } @article {pmid30400851, year = {2018}, author = {Zhang, D and He, JY and Haddadi, P and Zhu, JH and Yang, ZH and Ma, L}, title = {Genome sequence of the potato pathogenic fungus Alternaria solani HWC-168 reveals clues for its conidiation and virulence.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {176}, pmid = {30400851}, issn = {1471-2180}, abstract = {BACKGROUND: Alternaria solani is a known air-born deuteromycete fungus with a polycyclic life cycle and is the causal agent of early blight that causes significant yield losses of potato worldwide. However, the molecular mechanisms underlying the conidiation and pathogenicity remain largely unknown.

RESULTS: We produced a high-quality genome assembly of A. solani HWC-168 that was isolated from a major potato-producing region of Northern China, which facilitated a comprehensive gene annotation, the accurate prediction of genes encoding secreted proteins and identification of conidiation-related genes. The assembled genome of A. solani HWC-168 has a genome size 32.8 Mb and encodes 10,358 predicted genes that are highly similar with related Alternaria species including Alternaria arborescens and Alternaria brassicicola. We identified conidiation-related genes in the genome of A. solani HWC-168 by searching for sporulation-related homologues identified from Aspergillus nidulans. A total of 975 secreted protein-encoding genes, which might act as virulence factors, were identified in the genome of A. solani HWC-168. The predicted secretome of A. solani HWC-168 possesses 261 carbohydrate-active enzymes (CAZy), 119 proteins containing RxLx[EDQ] motif and 27 secreted proteins unique to A. solani.

CONCLUSIONS: Our findings will facilitate the identification of conidiation- and virulence-related genes in the genome of A. solani. This will permit new insights into understanding the molecular mechanisms underlying the A. solani-potato pathosystem and will add value to the global fungal genome database.}, } @article {pmid30400848, year = {2018}, author = {Warris, S and Schijlen, E and van de Geest, H and Vegesna, R and Hesselink, T and Te Lintel Hekkert, B and Sanchez Perez, G and Medvedev, P and Makova, KD and de Ridder, D}, title = {Correcting palindromes in long reads after whole-genome amplification.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {798}, pmid = {30400848}, issn = {1471-2164}, support = {DBI-1356529//National Science Foundation/ ; 1T32GM102057-0A1//National Institutes of Health/ ; IIS-1421908//National Science Foundation/ ; DBI-ABI 0965596//National Science Foundation/ ; CCF-1439057//National Science Foundation/ ; IIS-1453527//National Science Foundation/ ; T32 GM102057/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Next-generation sequencing requires sufficient DNA to be available. If limited, whole-genome amplification is applied to generate additional amounts of DNA. Such amplification often results in many chimeric DNA fragments, in particular artificial palindromic sequences, which limit the usefulness of long sequencing reads.

RESULTS: Here, we present Pacasus, a tool for correcting such errors. Two datasets show that it markedly improves read mapping and de novo assembly, yielding results similar to these that would be obtained with non-amplified DNA.

CONCLUSIONS: With Pacasus long-read technologies become available for sequencing targets with very small amounts of DNA, such as single cells or even single chromosomes.}, } @article {pmid30400819, year = {2018}, author = {Noviello, TMR and Di Liddo, A and Ventola, GM and Spagnuolo, A and D'Aniello, S and Ceccarelli, M and Cerulo, L}, title = {Detection of long non-coding RNA homology, a comparative study on alignment and alignment-free metrics.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {407}, pmid = {30400819}, issn = {1471-2105}, support = {FIRB2012-RBFR12QW4I//FIRB2012/ ; }, mesh = {Animals ; *Conserved Sequence ; *Gene Expression Regulation ; *Genome ; Humans ; Mice ; RNA, Long Noncoding/*genetics ; Sequence Alignment/*methods ; Zebrafish/genetics ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) represent a novel class of non-coding RNAs having a crucial role in many biological processes. The identification of long non-coding homologs among different species is essential to investigate such roles in model organisms as homologous genes tend to retain similar molecular and biological functions. Alignment-based metrics are able to effectively capture the conservation of transcribed coding sequences and then the homology of protein coding genes. However, unlike protein coding genes the poor sequence conservation of long non-coding genes makes the identification of their homologs a challenging task.

RESULTS: In this study we compare alignment-based and alignment-free string similarity metrics and look at promoter regions as a possible source of conserved information. We show that promoter regions encode relevant information for the conservation of long non-coding genes across species and that such information is better captured by alignment-free metrics. We perform a genome wide test of this hypothesis in human, mouse, and zebrafish.

CONCLUSIONS: The obtained results persuaded us to postulate the new hypothesis that, unlike protein coding genes, long non-coding genes tend to preserve their regulatory machinery rather than their transcribed sequence. All datasets, scripts, and the prediction tools adopted in this study are available at https://github.com/bioinformatics-sannio/lncrna-homologs .}, } @article {pmid30400817, year = {2018}, author = {Lindfors, E and van Dam, JCJ and Lam, CMC and Zondervan, NA and Martins Dos Santos, VAP and Suarez-Diez, M}, title = {SyNDI: synchronous network data integration framework.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {403}, pmid = {30400817}, issn = {1471-2105}, support = {305340//FP7 Health (BE)/ ; }, mesh = {Algorithms ; Animals ; Computational Biology/*methods ; *Gene Expression Regulation, Bacterial ; *Gene Regulatory Networks ; Humans ; Mice ; Models, Biological ; Mycobacterium tuberculosis/*genetics ; *Software ; Staphylococcus aureus/*genetics ; }, abstract = {BACKGROUND: Systems biology takes a holistic approach by handling biomolecules and their interactions as big systems. Network based approach has emerged as a natural way to model these systems with the idea of representing biomolecules as nodes and their interactions as edges. Very often the input data come from various sorts of omics analyses. Those resulting networks sometimes describe a wide range of aspects, for example different experiment conditions, species, tissue types, stimulating factors, mutants, or simply distinct interaction features of the same network produced by different algorithms. For these scenarios, synchronous visualization of more than one distinct network is an excellent mean to explore all the relevant networks efficiently. In addition, complementary analysis methods are needed and they should work in a workflow manner in order to gain maximal biological insights.

RESULTS: In order to address the aforementioned needs, we have developed a Synchronous Network Data Integration (SyNDI) framework. This framework contains SyncVis, a Cytoscape application for user-friendly synchronous and simultaneous visualization of multiple biological networks, and it is seamlessly integrated with other bioinformatics tools via the Galaxy platform. We demonstrated the functionality and usability of the framework with three biological examples - we analyzed the distinct connectivity of plasma metabolites in networks associated with high or low latent cardiovascular disease risk; deeper insights were obtained from a few similar inflammatory response pathways in Staphylococcus aureus infection common to human and mouse; and regulatory motifs which have not been reported associated with transcriptional adaptations of Mycobacterium tuberculosis were identified.

CONCLUSIONS: Our SyNDI framework couples synchronous network visualization seamlessly with additional bioinformatics tools. The user can easily tailor the framework for his/her needs by adding new tools and datasets to the Galaxy platform.}, } @article {pmid30400816, year = {2018}, author = {Saito, T and Hirano, T and Prozorova, L and Tu Do, V and Sulikowska-Drozd, A and Sitnikova, T and Surenkhorloo, P and Yamazaki, D and Morii, Y and Kameda, Y and Fukuda, H and Chiba, S}, title = {Phylogeography of freshwater planorbid snails reveals diversification patterns in Eurasian continental islands.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {164}, pmid = {30400816}, issn = {1471-2148}, mesh = {Animals ; Bayes Theorem ; *Biodiversity ; DNA, Mitochondrial/genetics ; *Fresh Water ; *Islands ; Likelihood Functions ; Phylogeny ; *Phylogeography ; Snails/*classification/genetics ; Species Specificity ; Time Factors ; }, abstract = {BACKGROUND: Islands have traditionally been the centre of evolutionary biological research, but the dynamics of immigration and differentiation at continental islands have not been well studied. Therefore, we focused on the Japanese archipelago, the continental islands located at the eastern end of the Eurasian continent. While the Japanese archipelago is characterised by high biodiversity and rich freshwater habitats, the origin and formation mechanisms of its freshwater organisms are not clear. In order to clarify the history of the planorbid gastropod fauna, we conducted phylogenetic analysis, divergence time estimation, ancestral state reconstruction, and lineage diversity estimations.

RESULTS: Our analyses revealed the formation process of the planorbid fauna in the Japanese archipelago. Most lineages in the Japanese archipelago have closely related lineages on the continent, and the divergence within the Japanese lineages presumably occurred after the late Pliocene. In addition, each lineage is characterised by different phylogeographical patterns, suggesting that immigration routes from the continent to the Japanese archipelago differ among lineages. Furthermore, a regional lineage diversity plot showed that the present diversity in the Japanese archipelago potentially reflects the differentiation of lineages within the islands after the development of the Japanese archipelago.

CONCLUSIONS: Although additional taxon sampling and genetic analysis focused on each lineage are needed, our results suggest that immigration from multiple routes just prior to the development of the Japanese archipelago and subsequent diversification within the islands are major causes of the present-day diversity of the Japanese planorbid fauna.}, } @article {pmid30400815, year = {2018}, author = {Lu, M and Seeve, CM and Loopstra, CA and Krutovsky, KV}, title = {Exploring the genetic basis of gene transcript abundance and metabolite levels in loblolly pine (Pinus taeda L.) using association mapping and network construction.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {100}, pmid = {30400815}, issn = {1471-2156}, support = {2011-68002-30185//USDA National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: Identifying genetic variations that shape important complex traits is fundamental to the genetic improvement of important forest tree species, such as loblolly pine (Pinus taeda L.), which is one of the most commonly planted forest tree species in the southern U.S. Gene transcripts and metabolites are important regulatory intermediates that link genetic variations to higher-order complex traits such as wood development and drought response. A few prior studies have associated intermediate phenotypes including mRNA expression and metabolite levels with a limited number of molecular markers, but the identification of genetic variations that regulate intermediate phenotypes needs further investigation.

RESULTS: We identified 1841 single nucleotide polymorphisms (SNPs) associated with 191 gene expression mRNA phenotypes and 524 SNPs associated with 53 metabolite level phenotypes using 2.8 million exome-derived SNPs. The identified SNPs reside in genes with a wide variety of functions. We further integrated the identified SNPs and the associated expressed genes and metabolites into networks. We described the SNP-SNP interactions that significantly impacted the gene transcript abundance and metabolite level in the networks. Key loci and genes in the wood development and drought response networks were identified and analyzed.

CONCLUSIONS: This work provides new candidate genes for research on the genetic basis of gene expression and metabolism linked to wood development and drought response in loblolly pine and highlights the efficiency of using association-mapping-based networks to discover candidate genes with important roles in complex biological processes.}, } @article {pmid30400814, year = {2018}, author = {Tang, YT and Huang, YY and Li, JH and Qin, SH and Xu, Y and An, TX and Liu, CC and Wang, Q and Zheng, L}, title = {Alterations in exosomal miRNA profile upon epithelial-mesenchymal transition in human lung cancer cell lines.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {802}, pmid = {30400814}, issn = {1471-2164}, support = {81371901//National Natural Science Foundation of China (CN)/ ; 81702273//National Natural Science Foundation of China/ ; 1563000220//Science and Technology Program of Guangzhou/ ; }, abstract = {BACKGROUND: Epithelial-mesenchymal transition (EMT) is regarded as a critical event during tumor metastasis. Recent studies have revealed changes and the contributions of proteins in/on exosomes during EMT. Besides proteins, microRNA (miRNA) is another important functional component of exosomes. We hypothesized that the miRNA profile of exosomes may change following EMT and these exosomal miRNAs may in return promote EMT, migration and invasion of cancer cells.

RESULTS: The small RNA profile of exosomes was altered following EMT. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that the specific miRNAs of M-exosomes have the potential to drive signal transduction networks in EMT and cancer progression. Co-culture experiments confirmed that M-exosomes can enter epithelial cells and promote migration, invasion and expression of mesenchymal markers in the recipient cells.

CONCLUSION: Our results reveal changes in the function and miRNA profile of exosomes upon EMT. M-exosomes can promote transfer of the malignant (mesenchymal) phenotype to epithelial recipient cells. Further, the miRNAs specifically expressed in M-exosomes are associated with EMT and metastasis, and may serve as new biomarkers for EMT-like processes in lung cancer.}, } @article {pmid30400813, year = {2018}, author = {Chen, Y and Li, X and Su, L and Chen, X and Zhang, S and Xu, X and Zhang, Z and Chen, Y and XuHan, X and Lin, Y and Lai, Z}, title = {Genome-wide identification and characterization of long non-coding RNAs involved in the early somatic embryogenesis in Dimocarpus longan Lour.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {805}, pmid = {30400813}, issn = {1471-2164}, support = {20151104//New Century Excellent Talents in Fujian Province University/ ; 2015J06004//the Natural Science Funds for Distinguished Young Scholars in Fujian Province/ ; 31672127//the National Natural Science Foundation of China/ ; 31572088//the National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in variable cleavage, transcriptional interference, regulation of DNA methylation and protein modification. However, the regulation of lncRNAs in plant somatic embryos remains unclear. The longan (Dimocarpus longan) somatic embryogenesis (SE) system is a good system for research on longan embryo development.

RESULTS: In this study, 7643 lncRNAs obtained during early SE in D. longan were identified by high-throughput sequencing, among which 6005 lncRNAs were expressed. Of the expressed lncRNAs, 4790 were found in all samples and 160 were specifically expressed in embryogenic callus (EC), 154 in incomplete embryogenic compact structures (ICpECs), and 376 in globular embryos (GEs). We annotated the 6005 expressed lncRNAs, and 1404 lncRNAs belonged to 506 noncoding RNA (ncRNA) families and 4682 lncRNAs were predicted to target protein-coding genes. The target genes included 5051 cis-regulated target genes (5712 pairs) and 1605 trans-regulated target genes (3618 pairs). KEGG analysis revealed that most of the differentially expressed target genes (mRNAs) of the lncRNAs were enriched in the "plant-pathogen interaction" and "plant hormone signaling" pathways during early longan SE. Real-time quantitative PCR confirmed that 20 selected lncRNAs showed significant differences in expression and that five lncRNAs were related to auxin response factors. Compared with the FPKM expression trends, 16 lncRNA expression trends were the same in qPCR. In lncRNA-miRNA-mRNA relationship prediction, 40 lncRNAs were predicted to function as eTMs for 15 miRNAs and 7 lncRNAs were identified as potential miRNA precursors. In addition, we verified the lncRNA-miRNA-mRNA regulatory relationships by transient expression of miRNAs (miR172a, miR159a.1 and miR398a).

CONCLUSION: Analyses of lncRNAs during early longan SE showed that differentially expressed lncRNAs were involved in expression regulation at each SE stage, and may form a regulatory network with miRNAs and mRNAs. These findings provide new insights into lncRNAs and lay a foundation for future functional analysis of lncRNAs during early longan SE.}, } @article {pmid30400812, year = {2018}, author = {Kumar, MS and Slud, EV and Okrah, K and Hicks, SC and Hannenhalli, S and Corrada Bravo, H}, title = {Analysis and correction of compositional bias in sparse sequencing count data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {799}, pmid = {30400812}, issn = {1471-2164}, support = {K99 HG009007/HG/NHGRI NIH HHS/United States ; R01 RR021967/RR/NCRR NIH HHS/United States ; GM114267//National Institutes of Health/ ; R01 GM083084/GM/NIGMS NIH HHS/United States ; HG005220//National Institutes of Health/ ; R01 HG005220/HG/NHGRI NIH HHS/United States ; R21 GM107683/GM/NIGMS NIH HHS/United States ; 1564785//National Science Foundation (US)/ ; R01 GM114267/GM/NIGMS NIH HHS/United States ; GM083084//National Institutes of Health/ ; R01 GM103552/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Count data derived from high-throughput deoxy-ribonucliec acid (DNA) sequencing is frequently used in quantitative molecular assays. Due to properties inherent to the sequencing process, unnormalized count data is compositional, measuring relative and not absolute abundances of the assayed features. This compositional bias confounds inference of absolute abundances. Commonly used count data normalization approaches like library size scaling/rarefaction/subsampling cannot correct for compositional or any other relevant technical bias that is uncorrelated with library size.

RESULTS: We demonstrate that existing techniques for estimating compositional bias fail with sparse metagenomic 16S count data and propose an empirical Bayes normalization approach to overcome this problem. In addition, we clarify the assumptions underlying frequently used scaling normalization methods in light of compositional bias, including scaling methods that were not designed directly to address it.

CONCLUSIONS: Compositional bias, induced by the sequencing machine, confounds inferences of absolute abundances. We present a normalization technique for compositional bias correction in sparse sequencing count data, and demonstrate its improved performance in metagenomic 16s survey data. Based on the distribution of technical bias estimates arising from several publicly available large scale 16s count datasets, we argue that detailed experiments specifically addressing the influence of compositional bias in metagenomics are needed.}, } @article {pmid30400811, year = {2018}, author = {Moné, Y and Nhim, S and Gimenez, S and Legeai, F and Seninet, I and Parrinello, H and Nègre, N and d'Alençon, E}, title = {Characterization and expression profiling of microRNAs in response to plant feeding in two host-plant strains of the lepidopteran pest Spodoptera frugiperda.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {804}, pmid = {30400811}, issn = {1471-2164}, support = {ANR-12-BSV7-0004-01//Agence Nationale de la Recherche/ ; ANR-10-INBS-09//Agence Nationale de la Recherche/ ; }, abstract = {BACKGROUND: A change in the environment may impair development or survival of living organisms leading them to adapt to the change. The resulting adaptation trait may reverse, or become fixed in the population leading to evolution of species. Deciphering the molecular basis of adaptive traits can thus give evolutionary clues. In phytophagous insects, a change in host-plant range can lead to emergence of new species. Among them, Spodoptera frugiperda is a major agricultural lepidopteran pest consisting of two host-plant strains having diverged 3 MA, based on mitochondrial markers. In this paper, we address the role of microRNAs, important gene expression regulators, in response to host-plant change and in adaptive evolution.

RESULTS: Using small RNA sequencing, we characterized miRNA repertoires of the corn (C) and rice (R) strains of S. frugiperda, expressed during larval development on two different host-plants, corn and rice, in the frame of reciprocal transplant experiments. We provide evidence for 76 and 68 known miRNAs in C and R strains and 139 and 171 novel miRNAs. Based on read counts analysis, 34 of the microRNAs were differentially expressed in the C strain larvae fed on rice as compared to the C strain larvae fed on corn. Twenty one were differentially expressed on rice compared to corn in R strain. Nine were differentially expressed in the R strain compared to C strain when reared on corn. A similar ratio of microRNAs was differentially expressed between strains on rice. We could validate experimentally by QPCR, variation in expression of the most differentially expressed candidates. We used bioinformatics methods to determine the target mRNAs of known microRNAs. Comparison with the mRNA expression profile during similar reciprocal transplant experiment revealed potential mRNA targets of these host-plant regulated miRNAs.

CONCLUSIONS: In the current study, we performed the first systematic analysis of miRNAs in Lepidopteran pests feeding on host-plants. We identified a set of the differentially expressed miRNAs that respond to the plant diet, or differ constitutively between the two host plant strains. Among the latter, the ones that are also deregulated in response to host-plant are molecular candidates underlying a complex adaptive trait.}, } @article {pmid30400810, year = {2018}, author = {Pornsukarom, S and van Vliet, AHM and Thakur, S}, title = {Whole genome sequencing analysis of multiple Salmonella serovars provides insights into phylogenetic relatedness, antimicrobial resistance, and virulence markers across humans, food animals and agriculture environmental sources.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {801}, pmid = {30400810}, issn = {1471-2164}, support = {NPB-556678//National Pork Board/ ; CPS-201400969-01//Center for Produce Safety/ ; }, abstract = {BACKGROUND: Salmonella enterica is a significant foodborne pathogen, which can be transmitted via several distinct routes, and reports on acquisition of antimicrobial resistance (AMR) are increasing. To better understand the association between human Salmonella clinical isolates and the potential environmental/animal reservoirs, whole genome sequencing (WGS) was used to investigate the epidemiology and AMR patterns within Salmonella isolates from two adjacent US states.

RESULTS: WGS data of 200 S. enterica isolates recovered from human (n = 44), swine (n = 32), poultry (n = 22), and farm environment (n = 102) were used for in silico prediction of serovar, distribution of virulence genes, and phylogenetically clustered using core genome single nucleotide polymorphism (SNP) and feature frequency profiling (FFP). Furthermore, AMR was studied both by genotypic prediction using five curated AMR databases, and compared to phenotypic AMR using broth microdilution. Core genome SNP-based and FFP-based phylogenetic trees showed consistent clustering of isolates into the respective serovars, and suggested clustering of isolates based on the source of isolation. The overall correlation of phenotypic and genotypic AMR was 87.61% and 97.13% for sensitivity and specificity, respectively. AMR and virulence genes clustered with the Salmonella serovars, while there were also associations between the presence of virulence genes in both animal/environmental isolates and human clinical samples.

CONCLUSIONS: WGS is a helpful tool for Salmonella phylogenetic analysis, AMR and virulence gene predictions. The clinical isolates clustered closely with animal and environmental isolates, suggesting that animals and environment are potential sources for dissemination of AMR and virulence genes between Salmonella serovars.}, } @article {pmid30400809, year = {2018}, author = {Foroutan, M and Bhuva, DD and Lyu, R and Horan, K and Cursons, J and Davis, MJ}, title = {Single sample scoring of molecular phenotypes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {404}, pmid = {30400809}, issn = {1471-2105}, support = {NBCF-ECF-043-14//National Breast Cancer Foundation/ ; Melbourne Research Scholarship//University of Melbourne/ ; Melbourne Research Scholarship//University of Melbourne/ ; APP1128609//National Health and Medical Research Council/ ; AP1141361//National Health and Medical Research Council/ ; }, mesh = {Computational Biology/*methods ; Gene Expression Profiling/methods ; Humans ; Neoplasms/*genetics/*pathology ; *Phenotype ; *Precision Medicine ; *Transcriptome ; }, abstract = {BACKGROUND: Gene set scoring provides a useful approach for quantifying concordance between sample transcriptomes and selected molecular signatures. Most methods use information from all samples to score an individual sample, leading to unstable scores in small data sets and introducing biases from sample composition (e.g. varying numbers of samples for different cancer subtypes). To address these issues, we have developed a truly single sample scoring method, and associated R/Bioconductor package singscore (https://bioconductor.org/packages/singscore).

RESULTS: We use multiple cancer data sets to compare singscore against widely-used methods, including GSVA, z-score, PLAGE, and ssGSEA. Our approach does not depend upon background samples and scores are thus stable regardless of the composition and number of samples being scored. In contrast, scores obtained by GSVA, z-score, PLAGE and ssGSEA can be unstable when less data are available (NS < 25). The singscore method performs as well as the best performing methods in terms of power, recall, false positive rate and computational time, and provides consistently high and balanced performance across all these criteria. To enhance the impact and utility of our method, we have also included a set of functions implementing visual analysis and diagnostics to support the exploration of molecular phenotypes in single samples and across populations of data.

CONCLUSIONS: The singscore method described here functions independent of sample composition in gene expression data and thus it provides stable scores, which are particularly useful for small data sets or data integration. Singscore performs well across all performance criteria, and includes a suite of powerful visualization functions to assist in the interpretation of results. This method performs as well as or better than other scoring approaches in terms of its power to distinguish samples with distinct biology and its ability to call true differential gene sets between two conditions. These scores can be used for dimensional reduction of transcriptomic data and the phenotypic landscapes obtained by scoring samples against multiple molecular signatures may provide insights for sample stratification.}, } @article {pmid30400808, year = {2018}, author = {Hu, R and Xiao, J and Gu, T and Yu, X and Zhang, Y and Chang, J and Yang, G and He, G}, title = {Genome-wide identification and analysis of WD40 proteins in wheat (Triticum aestivum L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {803}, pmid = {30400808}, issn = {1471-2164}, support = {2016ZX08010004-004//National Genetically Modified New Varieties of Major Projects of China/ ; No. 31771418, 31570261//National Natural Science Foundation of China/ ; 2017AHB041//Key Project of Hubei Province/ ; }, abstract = {BACKGROUND: WD40 domains are abundant in eukaryotes, and they are essential subunits of large multiprotein complexes, which serve as scaffolds. WD40 proteins participate in various cellular processes, such as histone modification, transcription regulation, and signal transduction. WD40 proteins are regarded as crucial regulators of plant development processes. However, the systematic identification and analysis of WD40 proteins have yet to be reported in wheat.

RESULTS: In this study, a total of 743 WD40 proteins were identified in wheat, and they were grouped into 5 clusters and 11 subfamilies. Their gene structures, chromosomal locations, and evolutionary relationships were analyzed. Among them, 39 and 46 pairs of TaWD40s were distinguished as tandem duplication and segmental duplication genes. The 123 OsWD40s were identified to exhibit synteny with TaWD40s. TaWD40s showed the specific characteristics at the reproductive developmental stage, and numerous TaWD40s were involved in responses to stresses, including cold, heat, drought, and powdery mildew infection pathogen, based on the result of RNA-seq data analysis. The expression profiles of some TaWD40s in wheat seed development were confirmed through qRT-PCR technique.

CONCLUSION: In this study, 743 TaWD40s were identified from the wheat genome. As the main driving force of evolution, duplication events were observed, and homologous recombination was another driving force of evolution. The expression profiles of TaWD40s revealed their importance for the growth and development of wheat and their response to biotic and abiotic stresses. Our study also provided important information for further functional characterization of some WD40 proteins in wheat.}, } @article {pmid30400807, year = {2018}, author = {Salari, F and Zare-Mirakabad, F and Sadeghi, M and Rokni-Zadeh, H}, title = {Assessing the impact of exact reads on reducing the error rate of read mapping.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {406}, pmid = {30400807}, issn = {1471-2105}, support = {BS-1397-01-02//Institute for Research in Fundamental Sciences (IR)/ ; }, mesh = {*Algorithms ; Chromosome Mapping ; Computational Biology/*methods ; Escherichia coli/*genetics ; Escherichia coli Proteins/*genetics ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/methods ; Software ; }, abstract = {BACKGROUND: Nowadays, according to valuable resources of high-quality genome sequences, reference-based assembly methods with high accuracy and efficiency are strongly required. Many different algorithms have been designed for mapping reads onto a genome sequence which try to enhance the accuracy of reconstructed genomes. In this problem, one of the challenges occurs when some reads are aligned to multiple locations due to repetitive regions in the genomes.

RESULTS: In this paper, our goal is to decrease the error rate of rebuilt genomes by resolving multi-mapping reads. To achieve this purpose, we reduce the search space for the reads which can be aligned against the genome with mismatches, insertions or deletions to decrease the probability of incorrect read mapping. We propose a pipeline divided to three steps: ExactMapping, InExactMapping, and MergingContigs, where exact and inexact reads are aligned in two separate phases. We test our pipeline on some simulated and real data sets by applying some read mappers. The results show that the two-step mapping of reads onto the contigs generated by a mapper such as Bowtie2, BWA and Yara is effective in improving the contigs in terms of error rate.

CONCLUSIONS: Assessment results of our pipeline suggest that reducing the error rate of read mapping, not only can improve the genomes reconstructed by reference-based assembly in a reasonable running time, but can also have an impact on improving the genomes generated by de novo assembly. In fact, our pipeline produces genomes comparable to those of a multi-mapping reads resolution tool, namely MMR by decreasing the number of multi-mapping reads. Consequently, we introduce EIM as a post-processing step to genomes reconstructed by mappers.}, } @article {pmid30400805, year = {2018}, author = {Tchechmedjiev, A and Abdaoui, A and Emonet, V and Zevio, S and Jonquet, C}, title = {SIFR annotator: ontology-based semantic annotation of French biomedical text and clinical notes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {405}, pmid = {30400805}, issn = {1471-2105}, support = {ANR-12-JS02-01001//Agence Nationale de la Recherche (FR)/ ; ANR-15-CE23-0028//Agence Nationale de la Recherche (FR)/ ; 701771//H2020 European Research Council/ ; }, mesh = {*Abstracting and Indexing as Topic ; *Biological Ontologies ; *Data Analysis ; France ; Gene Expression Profiling ; *Health Records, Personal ; Humans ; Information Storage and Retrieval ; MEDLINE ; *Medical Informatics ; *Natural Language Processing ; *Semantics ; }, abstract = {BACKGROUND: Despite a wide adoption of English in science, a significant amount of biomedical data are produced in other languages, such as French. Yet a majority of natural language processing or semantic tools as well as domain terminologies or ontologies are only available in English, and cannot be readily applied to other languages, due to fundamental linguistic differences. However, semantic resources are required to design semantic indexes and transform biomedical (text)data into knowledge for better information mining and retrieval.

RESULTS: We present the SIFR Annotator (http://bioportal.lirmm.fr/annotator), a publicly accessible ontology-based annotation web service to process biomedical text data in French. The service, developed during the Semantic Indexing of French Biomedical Data Resources (2013-2019) project is included in the SIFR BioPortal, an open platform to host French biomedical ontologies and terminologies based on the technology developed by the US National Center for Biomedical Ontology. The portal facilitates use and fostering of ontologies by offering a set of services -search, mappings, metadata, versioning, visualization, recommendation- including for annotation purposes. We introduce the adaptations and improvements made in applying the technology to French as well as a number of language independent additional features -implemented by means of a proxy architecture- in particular annotation scoring and clinical context detection. We evaluate the performance of the SIFR Annotator on different biomedical data, using available French corpora -Quaero (titles from French MEDLINE abstracts and EMEA drug labels) and CépiDC (ICD-10 coding of death certificates)- and discuss our results with respect to the CLEF eHealth information extraction tasks.

CONCLUSIONS: We show the web service performs comparably to other knowledge-based annotation approaches in recognizing entities in biomedical text and reach state-of-the-art levels in clinical context detection (negation, experiencer, temporality). Additionally, the SIFR Annotator is the first openly web accessible tool to annotate and contextualize French biomedical text with ontology concepts leveraging a dictionary currently made of 28 terminologies and ontologies and 333 K concepts. The code is openly available, and we also provide a Docker packaging for easy local deployment to process sensitive (e.g., clinical) data in-house (https://github.com/sifrproject).}, } @article {pmid30399431, year = {2019}, author = {Kim, JI and Park, S and Chu, H and Lee, I and Bae, JY and Yoo, K and Kim, J and Lee, JY and Lee, N and Kim, M and Kim, JS and Hong, KW and Jun, KR and Lee, JN and Kim, K and Park, MS}, title = {Distinct molecular evolution of influenza H3N2 strains in the 2016/17 season and its implications for vaccine effectiveness.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {29-34}, doi = {10.1016/j.ympev.2018.10.042}, pmid = {30399431}, issn = {1095-9513}, abstract = {Influenza virus is a respiratory pathogen that causes seasonal epidemics by resulting in a considerable number of influenza-like illness (ILI) patients. During the 2016/17 season, ILI rates increased unusually earlier and higher than previous seasons in Korea, and most viral isolates were subtyped as H3N2 strains. Notably, the hemagglutinin (HA) of most Korean H3N2 strains retained newly introduced lysine signatures in HA antigenic sites A and D, compared with that of clade 3C.2a vaccine virus, which affected antigenic distances to the standard vaccine antisera in a hemagglutination inhibition assay. The neuraminidase (NA) of Korean H3N2 strains also harbored amino acid mutations. However, neither consistent amino acid mutations nor common phylogenetic clustering patterns were observed. These suggest that Korean H3N2 strains of the 2016/17 season might be distantly related with the vaccine virus both in genotypic and phenotypic classifications, which would adversely affect vaccine effectiveness.}, } @article {pmid30399430, year = {2019}, author = {Tang, P and Zhu, JC and Zheng, BY and Wei, SJ and Sharkey, M and Chen, XX and Vogler, AP}, title = {Mitochondrial phylogenomics of the Hymenoptera.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {8-18}, doi = {10.1016/j.ympev.2018.10.040}, pmid = {30399430}, issn = {1095-9513}, abstract = {The insect order Hymenoptera presents marvelous morphological and ecological diversity. Higher-level hymenopteran relationships remain controversial, even after recent phylogenomic analyses, as their taxon sampling was limited. To shed light on the origin and diversification of Hymenoptera, in particular the poorly studied Parasitica, we undertook phylogenetic analyses of 40 newly and 43 previously sequenced mitochondrial genomes representing all major clades of Hymenoptera. Various Bayesian inferences using different data partitions and phylogenetic methods recovered similar phylogenetic trees with strong statistical support for almost all nodes. Novel findings of the mitogenomic phylogeny mainly affected the three infraorders Ichneumonomorpha, Proctotrupomorpha and Evaniomorpha, the latter of which was split into three clades. Basal relationships of Parasitica recovered Stephanoidea + (Gasteruptiidae + Aulacidae) as the sister group to Ichneumonomorpha + (Trigonalyoidea + Megalyroidea). This entire clade is sister to Proctotrupomorpha, and Ceraphronoidea + Evaniidae is sister to Aculeata (stinging wasps). Our divergence time analysis indicates that major hymenopteran lineages originated in the Mesozoic. The radiation of early apocritans may have been triggered by the Triassic-Jurassic mass extinction; all extant families were present by the Cretaceous.}, } @article {pmid30399429, year = {2019}, author = {Maul, K and Krug, M and Nickrent, DL and Müller, KF and Quandt, D and Wicke, S}, title = {Morphology, geographic distribution, and host preferences are poor predictors of phylogenetic relatedness in the mistletoe genus Viscum L.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {106-115}, doi = {10.1016/j.ympev.2018.10.041}, pmid = {30399429}, issn = {1095-9513}, abstract = {Besides their alleged therapeutic effects, mistletoes of the genus Viscum L. (Viscaceae) are keystone species in many ecosystems across Europe, Africa, Asia and Australia because of their complex faunal interactions. We here reconstructed the evolutionary history of Viscum based on plastid and nuclear DNA sequence data. We obtained a highly resolved phylogenetic tree with ten well-supported clades, which we used to understand the spatio-temporal evolution of these aerial parasites and evaluate the contribution of reproductive switches and shifts in host ranges to their distribution and diversification. The genus Viscum originated in the early Eocene in Africa and appeared to have diversified mainly through geographic isolation, in several cases apparently coinciding with shifts in host preferences. During its evolution, switches in the reproductive mode from ancestral dioecy to monoecy imply an important role in the long-distance dispersal of the parasites from Africa to continental Asia and Australia. We also observed multiple cases of photosynthetic surface reduction (evolution of scale leaves) within the genus, probably indicative of increasing specialization associated with the parasitic lifestyle. Even compared with other parasitic angiosperms, where more host generalists than specialists exist, Viscum species are characterized by extraordinarily broad host ranges. Specialization on only a few hosts from a single family or order occurs rarely and is restricted mostly to very recently evolved lineages. The latter mostly derive from or are closely related to generalist parasites, implying that niche shifting to a new host represents an at least temporary evolutionary advantage in Viscum.}, } @article {pmid30398651, year = {2018}, author = {Haryono, M and Tsai, YM and Lin, CT and Huang, FC and Ye, YC and Deng, WL and Hwang, HH and Kuo, CH}, title = {Presence of an Agrobacterium-Type Tumor-Inducing Plasmid in Neorhizobium sp. NCHU2750 and the Link to Phytopathogenicity.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3188-3195}, pmid = {30398651}, issn = {1759-6653}, abstract = {The genus Agrobacterium contains a group of plant-pathogenic bacteria that have been developed into an important tool for genetic transformation of eukaryotes. To further improve this biotechnology application, a better understanding of the natural genetic variation is critical. During the process of isolation and characterization of wild-type strains, we found a novel strain (i.e., NCHU2750) that resembles Agrobacterium phenotypically but exhibits high sequence divergence in several marker genes. For more comprehensive characterization of this strain, we determined its complete genome sequence for comparative analysis and performed pathogenicity assays on plants. The results demonstrated that this strain is closely related to Neorhizobium in chromosomal organization, gene content, and molecular phylogeny. However, unlike the characterized species within Neorhizobium, which all form root nodules with legume hosts and are potentially nitrogen-fixing mutualists, NCHU2750 is a gall-forming pathogen capable of infecting plant hosts across multiple families. Intriguingly, this pathogenicity phenotype could be attributed to the presence of an Agrobacterium-type tumor-inducing plasmid in the genome of NCHU2750. These findings suggest that these different lineages within the family Rhizobiaceae are capable of transitioning between ecological niches by having novel combinations of replicons. In summary, this work expanded the genomic resources available within Rhizobiaceae and provided a strong foundation for future studies of this novel lineage. With an infectivity profile that is different from several representative Agrobacterium strains, this strain may be useful for comparative analysis to better investigate the genetic determinants of host range among these bacteria.}, } @article {pmid30398645, year = {2018}, author = {Wu, B and Xu, Z and Knudson, A and Carlson, A and Chen, N and Kovaka, S and LaButti, K and Lipzen, A and Pennachio, C and Riley, R and Schakwitz, W and Umezawa, K and Ohm, RA and Grigoriev, IV and Nagy, LG and Gibbons, J and Hibbett, D}, title = {Genomics and Development of Lentinus tigrinus: A White-Rot Wood-Decaying Mushroom with Dimorphic Fruiting Bodies.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3250-3261}, doi = {10.1093/gbe/evy246}, pmid = {30398645}, issn = {1759-6653}, abstract = {Lentinus tigrinus is a species of wood-decaying fungi (Polyporales) that has an agaricoid form (a gilled mushroom) and a secotioid form (puffball-like, with enclosed spore-bearing structures). Previous studies suggested that the secotioid form is conferred by a recessive allele of a single locus. We sequenced the genomes of one agaricoid (Aga) strain and one secotioid (Sec) strain (39.53-39.88 Mb, with 15,581-15,380 genes, respectively). We mated the Sec and Aga monokaryons, genotyped the progeny, and performed bulked segregant analysis (BSA). We also fruited three Sec/Sec and three Aga/Aga dikaryons, and sampled transcriptomes at four developmental stages. Using BSA, we identified 105 top candidate genes with nonsynonymous SNPs that cosegregate with fruiting body phenotype. Transcriptome analyses of Sec/Sec versus Aga/Aga dikaryons identified 907 differentially expressed genes (DEGs) along four developmental stages. On the basis of BSA and DEGs, the top 25 candidate genes related to fruiting body development span 1.5 Mb (4% of the genome), possibly on a single chromosome, although the precise locus that controls the secotioid phenotype is unresolved. The top candidates include genes encoding a cytochrome P450 and an ATP-dependent RNA helicase, which may play a role in development, based on studies in other fungi.}, } @article {pmid30398642, year = {2018}, author = {Mughal, MR and DeGiorgio, M}, title = {Localizing and classifying adaptive targets with trend filtered regression.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy205}, pmid = {30398642}, issn = {1537-1719}, abstract = {Identifying genomic locations of natural selection from sequence data is an ongoing challenge in population genetics. Current methods utilizing information combined from several summary statistics typically assume no correlation of summary statistics regardless of the genomic location from which they are calculated. However, due to linkage disequilibrium, summary statistics calculated at nearby genomic positions are highly correlated. We introduce an approach termed Trendsetter that accounts for the similarity of statistics calculated from adjacent genomic regions through trend filtering, while reducing the effects of multicollinearity through regularization. Our penalized regression framework has high power to detect sweeps, is capable of classifying sweep regions as either hard or soft, and can be applied to other selection scenarios as well. We find that Trendsetter is robust to both extensive missing data and strong background selection, and has comparable power to similar current approaches. Moreover, the model learned by Trendsetter can be viewed as a set of curves modeling the spatial distribution of summary statistics in the genome. Application to human genomic data revealed positively-selectedregions previously discovered such as LCT in Europeans and EDAR in East Asians. We also identified a number of novel candidates and show that populations with greater relatedness share more sweep signals.}, } @article {pmid30398620, year = {2018}, author = {Zhao, X and Su, L and Schaack, S and Sadd, BM and Sun, C}, title = {Tandem Repeats Contribute to Coding Sequence Variation in Bumblebees (Hymenoptera: Apidae).}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3176-3187}, pmid = {30398620}, issn = {1759-6653}, abstract = {Tandem repeats (TRs) are highly dynamic regions of the genome. Mutations at these loci represent a significant source of genetic variation and can facilitate rapid adaptation. Bumblebees are important pollinating insects occupying a wide range of habitats. However, to date, molecular mechanisms underlying the potential adaptation of bumblebees to diverse habitats are largely unknown. In the present study, we investigate how TRs contribute to genetic variation in bumblebees, thus potentially facilitating adaptation. We identified 26,595 TRs from the assembled 18 chromosome sequences of the buff-tailed bumblebee (Bombus terrestris), 66.7% of which reside in genic regions. We also compared TRs found in B. terrestris with those present in the assembled genome sequence of a congener, B. impatiens. We found that a total of 1,137 TRs were variable in length between the two sequenced bumblebee species, and further analysis reveals that 101 of them are located within coding regions. These 101 TRs are responsible for coding sequence variation and correspond to protein sequence length variation between the two bumblebee species. The variability of identified TRs in coding regions between bumblebees was confirmed by PCR amplification of a subset of loci. Functional classification of bumblebee genes where coding sequences include variable-length TRs suggests that a majority of genes (87%) that could be assigned to a protein class are related to transcriptional regulation. Our results show that TRs contribute to coding sequence variation in bumblebees, and thus may facilitate the adaptation of bumblebees through diversifying proteins involved in controlling gene expression.}, } @article {pmid30398619, year = {2018}, author = {Hagen, R and Verhoeve, VI and Gillespie, JJ and Driscoll, TP}, title = {Conjugative Transposons and Their Cargo Genes Vary across Natural Populations of Rickettsia buchneri Infecting the Tick Ixodes scapularis.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3218-3229}, doi = {10.1093/gbe/evy247}, pmid = {30398619}, issn = {1759-6653}, support = {R01 AI017828/AI/NIAID NIH HHS/United States ; R01 AI126853/AI/NIAID NIH HHS/United States ; R21 AI126108/AI/NIAID NIH HHS/United States ; }, abstract = {Rickettsia buchneri (formerly Rickettsia endosymbiont of Ixodes scapularis, or REIS) is an obligate intracellular endoparasite of the black-legged tick, the primary vector of Lyme disease in North America. It is noteworthy among the rickettsiae for its relatively large genome (1.8 Mb) and extraordinary proliferation of mobile genetic elements (MGEs), which comprise nearly 35% of its genome. Previous analysis of the R. buchneri genome identified several integrative conjugative elements named Rickettsiales amplified genomic elements (RAGEs); the composition of these RAGEs suggests that continued genomic invasions by MGEs facilitated the proliferation of rickettsial genes related to an intracellular lifestyle. In this study, we compare the genomic diversity at RAGE loci among sequenced rickettsiae that infect three related Ixodes spp., including two strains of R. buchneri and Rickettsia endosymbiont of Ixodes pacificus strain Humboldt, as well as a closely related species R. tamurae infecting Amblyomma testudinarium ticks. We further develop a novel multiplex droplet digital PCR assay and use it to quantify copy number ratios of chromosomal R. buchneri RAGE-A and RAGE-B to the single-copy gene gltA within natural populations of I. scapularis. Our results reveal substantial diversity among R. buchneri at these loci, both within individual ticks as well as in the I. scapularis population at large, demonstrating that genomic rearrangement of MGEs is an active process in these intracellular bacteria.}, } @article {pmid30398478, year = {2018}, author = {Singh, SP and Inderjit, and Singh, JS and Majumdar, S and Moyano, J and Nuñez, MA and Richardson, DM}, title = {Insights on the persistence of pines (Pinus species) in the Late Cretaceous and their increasing dominance in the Anthropocene.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10345-10359}, pmid = {30398478}, issn = {2045-7758}, abstract = {Although gymnosperms were nearly swept away by the rise of the angiosperms in the Late Cretaceous, conifers, and pines (Pinus species) in particular, survived and regained their dominance in some habitats. Diversification of pines into fire-avoiding (subgenus Haploxylon) and fire-adapted (subgenus Diploxylon) species occurred in response to abiotic and biotic factors in the Late Cretaceous such as competition with emerging angiosperms and changing fire regimes. Adaptations/traits that evolved in response to angiosperm-fuelled fire regimes and stressful environments in the Late Cretaceous were key to pine success and are also contributing to a new "pine rise" in some areas in the Anthropocene. Human-mediated activities exert both positive and negative impacts of range size and expansion and invasions of pines. Large-scale afforestation with pines, human-mediated changes to fire regimes, and other ecosystem processes are other contributing factors. We discuss traits that evolved in response to angiosperm-mediated fires and stressful environments in the Cretaceous and that continue to contribute to pine persistence and dominance and the numerous ways in which human activities favor pines.}, } @article {pmid30397851, year = {2018}, author = {Schwartz, AW}, title = {"Man and his Mission".}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {3}, pages = {273}, doi = {10.1007/s11084-018-9565-6}, pmid = {30397851}, issn = {1573-0875}, mesh = {Biological Science Disciplines/*trends ; Humans ; *Origin of Life ; Space Flight/*trends ; United States ; United States National Aeronautics and Space Administration ; }, } @article {pmid30397470, year = {2018}, author = {Gardner, B and Sollmann, R and Kumar, NS and Jathanna, D and Karanth, KU}, title = {State space and movement specification in open population spatial capture-recapture models.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10336-10344}, pmid = {30397470}, issn = {2045-7758}, abstract = {With continued global changes, such as climate change, biodiversity loss, and habitat fragmentation, the need for assessment of long-term population dynamics and population monitoring of threatened species is growing. One powerful way to estimate population size and dynamics is through capture-recapture methods. Spatial capture (SCR) models for open populations make efficient use of capture-recapture data, while being robust to design changes. Relatively few studies have implemented open SCR models, and to date, very few have explored potential issues in defining these models. We develop a series of simulation studies to examine the effects of the state-space definition and between-primary-period movement models on demographic parameter estimation. We demonstrate the implications on a 10-year camera-trap study of tigers in India. The results of our simulation study show that movement biases survival estimates in open SCR models when little is known about between-primary-period movements of animals. The size of the state-space delineation can also bias the estimates of survival in certain cases.We found that both the state-space definition and the between-primary-period movement specification affected survival estimates in the analysis of the tiger dataset (posterior mean estimates of survival ranged from 0.71 to 0.89). In general, we suggest that open SCR models can provide an efficient and flexible framework for long-term monitoring of populations; however, in many cases, realistic modeling of between-primary-period movements is crucial for unbiased estimates of survival and density.}, } @article {pmid30397469, year = {2018}, author = {Török, P and Penksza, K and Tóth, E and Kelemen, A and Sonkoly, J and Tóthmérész, B}, title = {Vegetation type and grazing intensity jointly shape grazing effects on grassland biodiversity.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10326-10335}, pmid = {30397469}, issn = {2045-7758}, abstract = {In the Palaearctic steppe zone, overgrazing was identified as one of the key drivers of declining grassland biodiversity, which underlines the necessity of the functional evaluation of increased grazing pressure on grassland vegetation. We tested the following hypotheses: (a) The effect of grazing intensity on species and functional diversity is strongly dependent on grassland type. (b) The magnitude of diet selectivity of grazers decreases with increasing grazing intensity. (c) Increasing grazing intensity increases evenness and functional evenness of the subjected grasslands. We analyzed vegetation patterns in four types of grasslands (Dry alkali short-grass steppes, Dry loess steppes, Non-alkali wet and Alkali wet grasslands) along an intensity gradient of beef cattle grazing at 73 sites in Hungary. Species richness, Shannon diversity, evenness, and four leaf traits were analyzed. We calculated community-weighted means for each single trait, and multi-trait functional richness, functional evenness, and divergence for all leaf traits. All species and functional diversity metrics were significantly affected by the grassland type, except leaf dry matter content. The effect of interaction between grazing intensity and grassland type was also significant for functional richness, functional evenness, community-weighted means of leaf area, and for species richness and evenness. An upward trend of specific leaf area was detected in all grasslands with the highest scores for the overgrazed sites, but the change was also grassland type dependent. The detected trend suggests that with increased intensity the overall selectivity of grazing decreased. We found that evenness was affected but functional evenness was not affected by grazing intensity. Functional evenness scores were more related to the grassland type than to changes in grazing intensity, and displayed a high variability. We stress that one-size-fits-all strategies cannot be recommended and actions should be fine-tuned at least at the level of grassland type.}, } @article {pmid30397468, year = {2018}, author = {Katz, AD and Taylor, SJ and Davis, MA}, title = {At the confluence of vicariance and dispersal: Phylogeography of cavernicolous springtails (Collembola: Arrhopalitidae, Tomoceridae) codistributed across a geologically complex karst landscape in Illinois and Missouri.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10306-10325}, pmid = {30397468}, issn = {2045-7758}, abstract = {The processes of vicariance and dispersal are central to our understanding of diversification, yet determining the factors that influence these processes remains a significant challenge in evolutionary biology. Caves offer ideal systems for examining the mechanisms underlying isolation, divergence, and speciation. Intrinsic ecological differences among cavernicolous organisms, such as the degree of cave dependence, are thought to be major factors influencing patterns of genetic isolation in caves. Using a comparative phylogeographic approach, we employed mitochondrial and nuclear markers to assess the evolutionary history of two ecologically distinct groups of terrestrial cave-dwelling springtails (Collembola) in the genera Pygmarrhopalites (Arrhopalitidae) and Pogonognathellus (Tomoceridae) that are codistributed in caves throughout the Salem Plateau-a once continuous karst region, now bisected by the Mississippi River Valley in Illinois and Missouri. Contrasting phylogeographic patterns recovered for troglobiotic Pygmarrhopalites sp. and eutroglophilic Pogonognathellus sp. suggests that obligate associations with cave habitats can restrict dispersal across major geographic barriers such as rivers and valleys, but may also facilitate subterranean dispersal between neighboring cave systems. Pygmarrhopalites sp. populations spanning the Mississippi River Valley were estimated to have diverged 2.9-4.8 Ma, which we attribute to vicariance resulting from climatic and geological processes involved in Mississippi River Valley formation beginning during the late Pliocene/early Pleistocene. Lastly, we conclude that the detection of many deeply divergent, morphologically cryptic, and microendemic lineages highlights our poor understanding of microarthropod diversity in caves and exposes potential conservation concerns.}, } @article {pmid30397467, year = {2018}, author = {Arnold, TW}, title = {Using ring-recovery and within-season recapture data to estimate fecundity and population growth.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10298-10305}, pmid = {30397467}, issn = {2045-7758}, abstract = {Tag-recovery data from organisms captured and marked post breeding are commonly used to estimate juvenile and adult survival. If annual fecundity could also be estimated, tagging studies such as European and North American bird-ringing schemes could provide all parameters needed to estimate population growth. I modified existing tag-recovery models to allow estimation of annual fecundity using age composition and recapture probabilities obtained during routine banding operations of northern pintails (Anas acuta) and dark-eyed juncos (Junco hyemalis), and I conducted simulations to assess estimator performance in relation to sample size. For pintails, population growth rate from band-recovery data (λ = 0.93, SD: 0.06) was similar but less precise than count-based estimates from the Waterfowl Breeding Pair and Habitat Survey (λ: 0.945, SE: 0.001). Models with temporal variation in vital rates indicated that annual population growth in pintails was driven primarily by variation in fecundity. Juncos had lower survival but greater fecundity, and their estimated population growth rate (λ: 1.01, SD: 0.19) was consistent with count-based surveys (λ: 0.986). Simulations indicated that reliable (CV < 0.10) estimates of fecundity could be obtained with >1,000 within-season live encounters. Although precision of survival estimates depended primarily on numbers of adult recoveries, estimates of fecundity and population growth were most sensitive to total number of live encounters. Synthesis and applications: Large-scale ring-recovery programs could be used to estimate annual fecundity in many species of birds, but the approach requires better data curation, including accurate assessment of age, better reporting of banding totals, and greater emphasis on obtaining and reporting within-season live encounters.}, } @article {pmid30397466, year = {2018}, author = {Wilschut, RA and Kostenko, O and Koorem, K and van der Putten, WH}, title = {Nematode community responses to range-expanding and native plant communities in original and new range soils.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10288-10297}, pmid = {30397466}, issn = {2045-7758}, abstract = {Many plant species expand their range to higher latitudes in response to climate change. However, it is poorly understood how biotic interactions in the new range differ from interactions in the original range. Here, in a mesocosm experiment, we analyze nematode community responses in original and new range soils to plant communities with either (a) species native in both the original and new range, (b) range-expanding species related to these natives (related range expanders), or (c) range expanders without native congeneric species in the new range (unrelated range expanders). We hypothesized that nematode community shifts between ranges are strongest for unrelated range expanders and minimal for plant species that are native in both ranges. As a part of these community shifts, we hypothesized that range expanders, but not natives, would accumulate fewer root-feeding nematodes in their new range compared to their original range. Analyses of responses of nematodes from both original and new ranges and comparison between range expanders with and without close relatives have not been made before. Our study reveals that none of the plant communities experienced evident nematode community shifts between the original and new range. However, in soils from the new range, root-feeding nematode communities of natives and related range expanders were more similar than in soils from the original range, whereas the nematode community of unrelated range expanders was distinct from the communities of natives and related range expanders in soils from both ranges. The abundances of root-feeding nematodes were comparable between the original and new range for all plant communities. Unexpectedly, unrelated range expanders overall accumulated most root-feeding nematodes, whereas related range expanders accumulated fewest. We conclude that nematode communities associated with native and range-expanding plant species differ between the original and the new range, but that range-expanding plant species do not accumulate fewer root-feeding nematodes in their new than in their original range.}, } @article {pmid30397465, year = {2018}, author = {Ni, P and Li, S and Lin, Y and Xiong, W and Huang, X and Zhan, A}, title = {Methylation divergence of invasive Ciona ascidians: Significant population structure and local environmental influence.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10272-10287}, pmid = {30397465}, issn = {2045-7758}, abstract = {The geographical expansion of invasive species usually leads to temporary and/or permanent changes at multiple levels (genetics, epigenetics, gene expression, etc.) to acclimatize to abiotic and/or biotic stresses in novel environments. Epigenetic variation such as DNA methylation is often involved in response to diverse local environments, thus representing one crucial mechanism to promote invasion success. However, evidence is scant on the potential role of DNA methylation variation in rapid environmental response and invasion success during biological invasions. In particular, DNA methylation patterns and possible contributions of varied environmental factors to methylation differentiation have been largely unknown in many invaders, especially for invasive species in marine systems where extremely complex interactions exist between species and surrounding environments. Using the methylation-sensitive amplification polymorphism (MSAP) technique, here we investigated population methylation structure at the genome level in two highly invasive model ascidians, Ciona robusta and C. intestinalis, collected from habitats with varied environmental factors such as temperature and salinity. We found high intrapopulation methylation diversity and significant population methylation differentiation in both species. Multiple analyses, such as variation partitioning analysis, showed that both genetic variation and environmental factors contributed to the observed DNA methylation variation. Further analyses found that 24 and 20 subepiloci were associated with temperature and/or salinity in C. robusta and C. intestinalis, respectively. All these results clearly showed significant methylation divergence among populations of both invasive ascidians, and varied local environmental factors, as well as genetic variation, were responsible for the observed DNA methylation patterns. The consistent findings in both species here suggest that DNA methylation, coupled with genetic variation, may facilitate local environmental adaptation during biological invasions, and DNA methylation variation molded by local environments may contribute to invasion success.}, } @article {pmid30397464, year = {2018}, author = {Alhaddad, H and Alhajeri, BH}, title = {SamplEase: a simple application for collection and organization of biological specimen data in the field.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10266-10271}, pmid = {30397464}, issn = {2045-7758}, abstract = {Careful collection and organization of biological specimens and their associated data are at the core of field research (e.g., ecology, genetics). Fieldwork data are often collected by handwriting or unsystematically via an electronic device (e.g., laptop), a process that is time-intensive, disorganized, and may lead to transcription errors, as data are copied to a more permanent repository. SamplEase is an iOS and Android application that is designed to ease the process of collecting biological specimen data in the field (data associated with biological samples, such as location, age, and sex). In addition to biological specimen data, SamplEase allows for the assignment of photographs to each collected sample, which provides visual records of each specimen in its environment. SamplEase outputs biological specimen data in a tabular format, facilitating subsequent analyses and dissemination. Despite the simplicity of SamplEase, no similar data management application is readily available for researchers.}, } @article {pmid30397463, year = {2018}, author = {Crocker, KC and Hunter, MD}, title = {Social density, but not sex ratio, drives ecdysteroid hormone provisioning to eggs by female house crickets (Acheta domesticus).}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10257-10265}, pmid = {30397463}, issn = {2045-7758}, abstract = {Social environment profoundly influences the fitness of animals, affecting their probability of survival to adulthood, longevity, and reproductive output. The social conditions experienced by parents at the time of reproduction can predict the social environments that offspring will face. Despite clear challenges in predicting future environmental conditions, adaptive maternal effects provide a mechanism of passing environmental information from parent to offspring and are now considered pervasive in natural systems. Maternal effects have been widely studied in vertebrates, especially in the context of social environment, and are often mediated by steroid hormone (SH) deposition to eggs. In insects, although many species dramatically alter phenotype and life-history traits in response to social density, the mechanisms of these alterations, and the role of hormone deposition by insect mothers into their eggs, remains unknown. In the experiments described here, we assess the effects of social environment on maternal hormone deposition to eggs in house crickets (Acheta domesticus). Specifically, we tested the hypotheses that variable deposition of ecdysteroid hormones (ESH) to eggs is affected by both maternal (a) social density and (b) social composition. We found that while maternal hormone deposition to eggs does not respond to social composition (sex ratio), it does reflect social density; females provision their eggs with higher ESH doses under low-density conditions. This finding is consistent with the interpretation that variable ESH provisioning is an adaptive maternal response to social environment and congruent with similar patterns of variable maternal provisioning across the tree of life. Moreover, our results confirm that maternal hormone provisioning may mediate delayed density dependence by introducing a time lag in the response of offspring phenotype to population size.}, } @article {pmid30397462, year = {2018}, author = {Pearse, AR and Hamilton, RJ and Choat, JH and Pita, J and Almany, G and Peterson, N and Hamilton, GS and Peterson, EE}, title = {Giant coral reef fishes display markedly different susceptibility to night spearfishing.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10247-10256}, pmid = {30397462}, issn = {2045-7758}, abstract = {The humphead wrasse (Cheilinus undulatus) and bumphead parrotfish (Bolbometopon muricatum) are two of the largest, most iconic fishes of Indo-Pacific coral reefs. Both species form prized components of subsistence and commercial fisheries and are vulnerable to overfishing. C. undulatus is listed as Endangered and B. muricatum as Vulnerable on the IUCN Red List of Threatened Species. We investigated how night spearfishing pressure and habitat associations affected both species in a relatively lightly exploited setting; the Kia fishing grounds, Isabel Province, Solomon Islands. We used fisheries-independent data from underwater visual census surveys and negative binomial models to estimate abundances of adult C. undulatus and B. muricatum as a function of spearfishing pressure and reef strata. Our results showed that, in Kia, night spearfishing pressure from free divers had no measurable effect on C. undulatus abundances, but abundances of B. muricatum were 3.6 times lower in areas of high spearfishing pressure, after accounting for natural variations due to habitat preferences. It is likely the species' different nocturnal aggregation behaviors, combined with the fishers' use of night spearfishing by spot-checking underpin these species' varying susceptibility. Our study highlights that B. muricatum is extremely susceptible to night spearfishing; however, we do not intend to draw conservation attention away from C. undulatus. Our data relate only to the Kia fishing grounds, where human population density is low, the spot-checking strategy is effective for reliably spearing large numbers of fish, particularly B. muricatum, and fisheries have only recently begun to be commercialized; such conditions are increasingly rare. Instead, we recommend that regional managers assess the state of their fisheries and the dynamics affecting the vulnerability of the fishes to fishing pressure based on local-scale, fisheries-independent data, where resources permit.}, } @article {pmid30397461, year = {2018}, author = {Guerrero, J and Byrne, AW and Lavery, J and Presho, E and Kelly, G and Courcier, EA and O'Keeffe, J and Fogarty, U and O'Meara, DB and Ensing, D and McCormick, C and Biek, R and Skuce, RA and Allen, AR}, title = {The population and landscape genetics of the European badger (Meles meles) in Ireland.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10233-10246}, pmid = {30397461}, issn = {2045-7758}, abstract = {The population genetic structure of free-ranging species is expected to reflect landscape-level effects. Quantifying the role of these factors and their relative contribution often has important implications for wildlife management. The population genetics of the European badger (Meles meles) have received considerable attention, not least because the species acts as a potential wildlife reservoir for bovine tuberculosis (bTB) in Britain and Ireland. Herein, we detail the most comprehensive population and landscape genetic study of the badger in Ireland to date-comprised of 454 Irish badger samples, genotyped at 14 microsatellite loci. Bayesian and multivariate clustering methods demonstrated continuous clinal variation across the island, with potentially distinct differentiation observed in Northern Ireland. Landscape genetic analyses identified geographic distance and elevation as the primary drivers of genetic differentiation, in keeping with badgers exhibiting high levels of philopatry. Other factors hypothesized to affect gene flow, including earth worm habitat suitability, land cover type, and the River Shannon, had little to no detectable effect. By providing a more accurate picture of badger population structure and the factors effecting it, these data can guide current efforts to manage the species in Ireland and to better understand its role in bTB.}, } @article {pmid30397460, year = {2018}, author = {Takeuchi, H and Savitzky, AH and Ding, L and de Silva, A and Das, I and Nguyen, TT and Tsai, TS and Jono, T and Zhu, GX and Mahaulpatha, D and Tang, Y and Mori, A}, title = {Evolution of nuchal glands, unusual defensive organs of Asian natricine snakes (Serpentes: Colubridae), inferred from a molecular phylogeny.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10219-10232}, pmid = {30397460}, issn = {2045-7758}, abstract = {A large body of evidence indicates that evolutionary innovations of novel organs have facilitated the subsequent diversification of species. Investigation of the evolutionary history of such organs should provide important clues for understanding the basis for species diversification. An Asian natricine snake, Rhabdophis tigrinus, possesses a series of unusual organs, called nuchal glands, which contain cardiotonic steroid toxins known as bufadienolides. Rhabdophis tigrinus sequesters bufadienolides from its toad prey and stores them in the nuchal glands as a defensive mechanism. Among more than 3,500 species of snakes, only 17 Asian natricine species are known to possess nuchal glands or their homologues. These 17 species belong to three nominal genera, Balanophis, Macropisthodon, and Rhabdophis. In Macropisthodon and Rhabdophis, however, species without nuchal glands also exist. To infer the evolutionary history of the nuchal glands, we investigated the molecular phylogenetic relationships among Asian natricine species with and without nuchal glands, based on variations in partial sequences of Mt-CYB, Cmos, and RAG1 (total 2,767 bp). Results show that all species with nuchal glands belong to a single clade (NGC). Therefore, we infer that the common ancestor of this clade possessed nuchal glands with no independent origins of the glands within the members. Our results also imply that some species have secondarily lost the glands. Given the estimated divergence time of related species, the ancestor of the nuchal gland clade emerged 19.18 mya. Our study shows that nuchal glands are fruitful subjects for exploring the evolution of novel organs. In addition, our analysis indicates that reevaluation of the taxonomic status of the genera Balanophis and Macropisthodon is required. We propose to assign all species belonging to the NGC to the genus Rhabdophis, pending further study.}, } @article {pmid30397459, year = {2018}, author = {Hartikainen, SM and Jach, A and Grané, A and Robson, TM}, title = {Assessing scale-wise similarity of curves with a thick pen: As illustrated through comparisons of spectral irradiance.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10206-10218}, pmid = {30397459}, issn = {2045-7758}, abstract = {Forest canopies create dynamic light environments in their understorey, where spectral composition changes among patterns of shade and sunflecks, and through the seasons with canopy phenology and sun angle. Plants use spectral composition as a cue to adjust their growth strategy for optimal resource use. Quantifying the ever-changing nature of the understorey light environment is technically challenging with respect to data collection. Thus, to capture the simultaneous variation occurring in multiple regions of the solar spectrum, we recorded spectral irradiance from forest understoreys over the wavelength range 300-800 nm using an array spectroradiometer. It is also methodologically challenging to analyze solar spectra because of their multi-scale nature and multivariate lay-out. To compare spectra, we therefore used a novel method termed thick pen transform (TPT), which is simple and visually interpretable. This enabled us to show that sunlight position in the forest understorey (i.e., shade, semi-shade, or sunfleck) was the most important factor in determining shape similarity of spectral irradiance. Likewise, the contributions of stand identity and time of year could be distinguished. Spectra from sunflecks were consistently the most similar, irrespective of differences in global irradiance. On average, the degree of cross-dependence increased with increasing scale, sometimes shifting from negative (dissimilar) to positive (similar) values. We conclude that the interplay of sunlight position, stand identity, and date cannot be ignored when quantifying and comparing spectral composition in forest understoreys. Technological advances mean that array spectroradiometers, which can record spectra contiguously over very short time intervals, are being widely adopted, not only to measure irradiance under pollution, clouds, atmospheric changes, and in biological systems, but also spectral changes at small scales in the photonics industry. We consider that TPT is an applicable method for spectral analysis in any field and can be a useful tool to analyze large datasets in general.}, } @article {pmid30397458, year = {2018}, author = {Calvert, J and McGonigle, C and Sethi, SA and Harris, B and Quinn, R and Grabowski, J}, title = {Dynamic occupancy modeling of temperate marine fish in area-based closures.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10192-10205}, pmid = {30397458}, issn = {2045-7758}, abstract = {Species distribution models (SDMs) are commonly used to model the spatial structure of species in the marine environment, however, most fail to account for detectability of the target species. This can result in underestimates of occupancy, where nondetection is conflated with absence. The site occupancy model (SOM) overcomes this failure by treating occupancy as a latent variable of the model and incorporates a detection submodel to account for variability in detection rates. These have rarely been applied in the context of marine fish and never for the multiseason dynamic occupancy model (DOM). In this study, a DOM is developed for a designated species of concern, cusk (Brosme brosme), over a four-season period. Making novel use of a high-resolution 3-dimensional hydrodynamic model, detectability of cusk is considered as a function of current speed and algae cover. Algal cover on the seabed is measured from video surveys to divide the study area into two distinct regions: those with canopy forming species of algae and those without (henceforth bottom types). Modeled estimates of the proportion of sites occupied in each season are 0.88, 0.45, 0.74, and 0.83. These are significantly greater than the proportion of occupied sites measured from underwater video observations which are 0.57, 0.28, 0.43, and 0.57. Individual fish are detected more frequently with increasing current speed in areas lacking canopy and less frequently with increasing current speed in areas with canopy. The results indicate that, where possible, SDM studies for all marine species should take account of detectability to avoid underestimating the proportion of sites occupied at a given study area. Sampling closed areas or areas of conservation often requires the use of nonphysical, low impact sampling methods like camera surveys. These methods inherently result in detection probabilities less than one, an issue compounded by time-varying features of the environment that are rarely accounted for marine studies. This work highlights the use of modeled hydrodynamics as a tool to correct some of this imbalance.}, } @article {pmid30397457, year = {2018}, author = {Singh, M and Evans, D and Chevance, JB and Tan, BS and Wiggins, N and Kong, L and Sakhoeun, S}, title = {Evaluating the ability of community-protected forests in Cambodia to prevent deforestation and degradation using temporal remote sensing data.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10175-10191}, pmid = {30397457}, issn = {2045-7758}, abstract = {Community forests are known to play an important role in preserving forests in Cambodia, a country that has seen rapid deforestation in recent decades. The detailed evaluation of the ability of community-protected forests to retain forest cover and prevent degradation in Cambodia will help to guide future conservation management. In this study, a combination of remotely sensing data was used to compare the temporal variation in forest structure for six different community forests located in the Phnom Kulen National Park (PKNP) in Cambodia and to assess how these dynamics vary between community-protected forests and a wider study area. Medium-resolution Landsat, ALOS PALSAR data, and high-resolution LiDAR data were used to study the spatial distribution of forest degradation patterns and their impacts on above-ground biomass (AGB) changes. Analysis of the remotely sensing data acquired at different spatial resolutions revealed that between 2012 and 2015, the community forests had higher forest cover persistence and lower rates of forest cover loss compared to the entire study area. Furthermore, they faced lower encroachment from cashew plantations compared to the wider landscape. Four of the six community forests showed a recovery in canopy gap fractions and subsequently, an increase in the AGB stock. The levels of degradation decreased in forests that had an increase in AGB values. However, all community forests experienced an increase in understory damage as a result of selective tree removal, and the community forests with the sharpest increase in understory damage experienced AGB losses. This is the first time multitemporal high-resolution LiDAR data have been used to analyze the impact of human-induced forest degradation on forest structure and AGB. The findings of this work indicate that while community-protected forests can improve conservation outcomes to some extent, more interventions are needed to curb the illegal selective logging of valuable timber trees.}, } @article {pmid30397456, year = {2018}, author = {Iserbyt, A and Griffioen, M and Borremans, B and Eens, M and Müller, W}, title = {How to quantify animal activity from radio-frequency identification (RFID) recordings.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10166-10174}, pmid = {30397456}, issn = {2045-7758}, abstract = {Automated animal monitoring via radio-frequency identification (RFID) technology allows efficient and extensive data sampling of individual activity levels and is therefore commonly used for ecological research. However, processing RFID data is still a largely unresolved problem, which potentially leads to inaccurate estimates for behavioral activity. One of the major challenges during data processing is to isolate independent behavioral actions from a set of superfluous, nonindependent detections. As a case study, individual blue tits (Cyanistes caeruleus) were simultaneously monitored during reproduction with both video recordings and RFID technology. We demonstrated how RFID data can be processed based on the time spent in- and outside a nest box. We then validated the number and timing of nest visits obtained from the processed RFID dataset by calibration against video recordings. The video observations revealed a limited overlap between the time spent in- and outside the nest box, with the least overlap at 23 s for both sexes. We then isolated exact arrival times from redundant RFID registrations by erasing all successive registrations within 23 s after the preceding registration. After aligning the processed RFID data with the corresponding video recordings, we observed a high accuracy in three behavioral estimates of parental care (individual nest visit rates, within-pair alternation and synchronization of nest visits). We provide a clear guideline for future studies that aim to implement RFID technology in their research. We argue that our suggested RFID data processing procedure improves the precision of behavioral estimates, despite some inevitable drawbacks inherent to the technology. Our method is useful, not only for other cavity breeding birds, but for a wide range of (in)vertebrate species that are large enough to be fitted with a tag and that regularly pass near or through a fixed antenna.}, } @article {pmid30397455, year = {2018}, author = {Winter, S and Fennessy, J and Janke, A}, title = {Limited introgression supports division of giraffe into four species.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10156-10165}, pmid = {30397455}, issn = {2045-7758}, abstract = {All giraffe (Giraffa) were previously assigned to a single species (G. camelopardalis) and nine subspecies. However, multi-locus analyses of all subspecies have shown that there are four genetically distinct clades and suggest four giraffe species. This conclusion might not be fully accepted due to limited data and lack of explicit gene flow analyses. Here, we present an extended study based on 21 independent nuclear loci from 137 individuals. Explicit gene flow analyses identify less than one migrant per generation, including between the closely related northern and reticulated giraffe. Thus, gene flow analyses and population genetics of the extended dataset confirm four genetically distinct giraffe clades and support four independent giraffe species. The new findings support a revision of the IUCN classification of giraffe taxonomy. Three of the four species are threatened with extinction, and mostly occurring in politically unstable regions, and as such, require the highest conservation support possible.}, } @article {pmid30397454, year = {2018}, author = {Christianson, D and Becker, MS and Brennan, A and Creel, S and Dröge, E and M'soka, J and Mukula, T and Schuette, P and Smit, D and Watson, F}, title = {Foraging investment in a long-lived herbivore and vulnerability to coursing and stalking predators.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10147-10155}, pmid = {30397454}, issn = {2045-7758}, abstract = {Allocating resources to growth and reproduction requires grazers to invest time in foraging, but foraging promotes dental senescence and constrains expression of proactive antipredator behaviors such as vigilance. We explored the relationship between carnivore prey selection and prey foraging effort using incisors collected from the kills of coursing and stalking carnivores. We predicted that prey investing less effort in foraging would be killed more frequently by coursers, predators that often exploit physical deficiencies. However, such prey could expect delayed dental senescence. We predicted that individuals investing more effort in foraging would be killed more frequently by stalkers, predators that often exploit behavioral vulnerabilities. Further these prey could expect earlier dental senescence. We tested these predictions by comparing variation in age-corrected tooth wear, a proxy of cumulative foraging effort, in adult (3.4-11.9 years) wildebeest killed by coursing and stalking carnivores. Predator type was a strong predictor of age-corrected tooth wear within each gender. We found greater foraging effort and earlier expected dental senescence, equivalent to 2.6 additional years of foraging, in female wildebeest killed by stalkers than in females killed by coursers. However, male wildebeest showed the opposite pattern with the equivalent of 2.4 years of additional tooth wear in males killed by coursers as compared to those killed by stalkers. Sex-specific variation in the effects of foraging effort on vulnerability was unexpected and suggests that behavioral and physical aspects of vulnerability may not be subject to the same selective pressures across genders in multipredator landscapes.}, } @article {pmid30397453, year = {2018}, author = {Querejeta, M and Castresana, J}, title = {Evolutionary history of the endemic water shrew Neomys anomalus: Recurrent phylogeographic patterns in semi-aquatic mammals of the Iberian Peninsula.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10138-10146}, pmid = {30397453}, issn = {2045-7758}, abstract = {The Cabrera's water shrew (Neomys anomalus) is a small semi-aquatic mammal whose taxonomic status was recently elevated from subspecies to species; as a consequence of this change, this species is now endemic to the Iberian Peninsula. In this study, we looked at its evolutionary history by combining phylogeography, the spatial distribution of genetic diversity, and species distribution modeling. To perform these analyses, we used noninvasive samples collected across the species distribution range and sequenced partial mitochondrial cytochrome b and D-loop genes. Maximum-likelihood and Bayesian phylogenetic trees derived from these sequences indicated that N. anomalus is divided into two main phylogroups that correlate strongly with geography, with two contact zones between the groups that showed limited spatial mixing between them. River basins were responsible for only a small percentage of the structure of the genetic diversity of this species despite its riparian habitat. The nucleotide diversity variation map showed the highest genetic diversity to be in the north of the Iberian Peninsula. Finally, species distribution modeling allowed the inference of an optimal area during the Last Interglacial in the north of the Iberian Peninsula, and multiple glacial refugia during the Last Glacial Maximum. The phylogeographic pattern of N. anomalus is strikingly similar to that of another semi-aquatic Iberian mammal, the Pyrenean desman (Galemys pyrenaicus), revealing how Pleistocene glaciations could have had equivalent effects on species of similar ecology and distribution. This phylogeographic structure is consistent with N. anomalus having been isolated for long periods in multiple glacial refugia within the Iberian Peninsula, in agreement with the "refugia-within-refugia" hypothesis, and further supporting its status as a distinct species.}, } @article {pmid30397452, year = {2018}, author = {Pilskog, HE and Sverdrup-Thygeson, A and Evju, M and Framstad, E and Birkemoe, T}, title = {Long-lasting effects of logging on beetles in hollow oaks.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10126-10137}, pmid = {30397452}, issn = {2045-7758}, abstract = {There is growing evidence that biodiversity is important for ecosystem functions. Thus, identification of habitat requirements essential for current species richness and abundance to persist is crucial. Hollow oaks (Quercus spp.) are biodiversity hot spots for deadwood-dependent insect species, and the main objective of this paper was to test the effect of habitat history and current habitat distribution at various spatial scales on the associated beetle community. We used a gradient spanning 40 km from the coast to inland areas reflecting historical logging intensity (later and lower intensities inland) through 500 years in Southern Norway, to investigate whether the historical variation in oak density is influencing the structure of beetle communities in hollow oaks today. We trapped beetles in 32 hollow oaks along this gradient in forested and seminatural landscapes over two summers. We found higher species richness and total abundance inland consistent with our expectation based on historic logging intensity. Scale-specific environmental variables also affected the response; beetle abundances were controlled by local conditions, whereas beetle species richness responded to habitat on the landscape scale. This indicates that long time continuity as well as large areas of favorable habitat is necessary to maintain beetle species richness through time in these highly long-lasting structures.}, } @article {pmid30397451, year = {2018}, author = {Zong, N and Geng, S and Duan, C and Shi, P and Chai, X and Zhang, X}, title = {The effects of warming and nitrogen addition on ecosystem respiration in a Tibetan alpine meadow: The significance of winter warming.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10113-10125}, pmid = {30397451}, issn = {2045-7758}, abstract = {In recent decades, global warming has become an indisputable fact on the Tibetan Plateau. Alpine ecosystems are very sensitive to global warming, and the impact may depend on the degree of atmospheric nitrogen (N) deposition. The previous studies have paid more attention to year-round warming, but the effect of winter warming has been unstudied. In this study, a manipulative experiment was conducted, consisting of warming and N addition. It was carried out since 2010 in an alpine meadow, and three types of warming treatments were set up: no warming (NW), year-round (YW), and winter warming (WW). Warming significantly increased air and soil temperature, but decreased soil moisture. Under no N addition, YW showed significantly decreased ecosystem respiration (Reco) in 2012, and WW decreased Reco in 2014. Under N addition, neither YW nor WW had significant effects on Reco, indicating that N addition compensated the negative effect of warming on Reco. Annually, YW and WW decreased ecosystem carbon (C) emissions, and the extent of the reduction was even larger under WW. Under no N addition, both YW and WW significantly decreased aboveground biomass. Moreover, especially under no N, YW and WW significantly decreased soil inorganic N. WW also had negative effects on soil microbial biomass C. Structure equation modeling showed that soil moisture was the most important factors controlling Reco, and soil inorganic N content and microbial biomass C could explain 46.6% and 16.8% of the variation of Reco. The findings indicate that soil property changes under warming had substantial effects on ecosystem C efflux. The inhibitory effects of winter warming on ecosystem C efflux were mainly attributed to the decline of soil N and microbial biomass. Thus, the effects of winter warming on ecosystem C emissions in this semiarid alpine meadow are not as serious as expected and largely depend on N deposition.}, } @article {pmid30397450, year = {2018}, author = {Liu, J and Liu, D and Xu, K and Gao, LM and Ge, XJ and Burgess, KS and Cadotte, MW}, title = {Biodiversity explains maximum variation in productivity under experimental warming, nitrogen addition, and grazing in mountain grasslands.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10094-10112}, pmid = {30397450}, issn = {2045-7758}, abstract = {Anthropogenic global warming, nitrogen addition, and overgrazing alter plant communities and threaten plant biodiversity, potentially impacting community productivity, especially in sensitive mountain grassland ecosystems. However, it still remains unknown whether the relationship between plant biodiversity and community productivity varies across different anthropogenic influences, and especially how changes in multiple biodiversity facets drive these impacts on productivity. Here, we measured different facets of biodiversity including functional and phylogenetic richness and evenness in mountain grasslands along an environmental gradient of elevation in Yulong Mountain, Yunnan, China. We combined biodiversity metrics in a series of linear mixed-effect models to determine the most parsimonious predictors for productivity, which was estimated by aboveground biomass in community. We examined how biodiversity-productivity relationships were affected by experimental warming, nitrogen addition, and livestock-grazing. Species richness, phylogenetic diversity, and single functional traits (leaf nitrogen content, mg/g) represented the most parsimonious combination in these scenarios, supporting a consensus that single-biodiversity metrics alone cannot fully explain ecosystem function. The biodiversity-productivity relationships were positive and strong, but the effects of treatment on biodiversity-productivity relationship were negligible. Our findings indicate that the strong biodiversity-productivity relationships are consistent in various anthropogenic drivers of environmental change.}, } @article {pmid30397449, year = {2018}, author = {Siers, SR and Yackel Adams, AA and Reed, RN}, title = {Behavioral differences following ingestion of large meals and consequences for management of a harmful invasive snake: A field experiment.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10075-10093}, pmid = {30397449}, issn = {2045-7758}, abstract = {Many snakes are uniquely adapted to ingest large prey at infrequent intervals. Digestion of large prey is metabolically and aerobically costly, and large prey boluses can impair snake locomotion, increasing vulnerability to predation. Cessation of foraging and use of refugia with microclimates facilitating digestion are expected to be strategies employed by free-ranging snakes to cope with the demands of digestion while minimizing risk of predation. However, empirical observations of such submergent behavior from field experiments are limited. The brown treesnake (Serpentes: Colubridae: Boiga irregularis) is a nocturnal, arboreal, colubrid snake that was accidentally introduced to the island of Guam, with ecologically and economically costly consequences. Because tools for brown treesnake damage prevention generally rely on snakes being visible or responding to lures or baits while foraging, cessation of foraging activities after feeding would complicate management. We sought to characterize differences in brown treesnake activity, movement, habitat use, and detectability following feeding of large meals (rodents 33% of the snake's unfed body mass) via radio telemetry, trapping, and visual surveys. Compared to unfed snakes, snakes in the feeding treatment group showed drastic decreases in hourly and nightly activity rates, differences in refuge height and microhabitat type, and a marked decrease in detectability by trapping and visual surveys. Depression of activity lasted approximately 5-7 days, a period that corresponds to previous studies of brown treesnake digestion and cycles of detectability. Our results indicate that management strategies for invasive brown treesnakes need to account for cycles of unavailability and underscore the importance of preventing spread of brown treesnakes to new environments where large prey are abundant and periods of cryptic behavior are likely to be frequent. Characterization of postfeeding behavior changes provides a richer understanding of snake ecology and foraging models for species that consume large prey.}, } @article {pmid30397448, year = {2018}, author = {Raquin, V and Henri, H and Vallat, M and Leulier, F and Gibert, P and Kremer, N}, title = {Development of a PCR-RFLP assay to identify Drosophila melanogaster among field-collected larvae.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10067-10074}, pmid = {30397448}, issn = {2045-7758}, abstract = {The fruit fly Drosophila melanogaster is a model organism to study several aspects of metazoan biology. Most of the work has been conducted in adult fruit flies, including laboratory and field-derived specimens, but Drosophila melanogaster larvae recently became a valuable model to better understand animal physiology, development, or host-microbe interactions. While adult flies can be easily assigned to a given Drosophila species based on morphological characteristics, such visual identification is more intricate at the larval stage. This could explain the limited number of studies focusing on larvae, especially field-derived samples. Here, we developed a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay that discriminates D. melanogaster from other ecologically relevant Drosophila species at the larval stage. The method, which targets the cytochrome oxidase I (COI) gene, was validated using laboratory-derived larvae from seven D. melanogaster populations originating from different geographic areas as well as six Drosophila species. We further validated this PCR-RFLP assay in a natural context, by identifying wild larvae collected in two locations in France. Notably, among all PCR-RFLP profiles that matched the D. melanogaster species, 100% were correctly identified, as confirmed by COI sequencing. In summary, our work provides a rapid, simple, and accurate molecular tool to identify D. melanogaster from field-collected larvae.}, } @article {pmid30397447, year = {2018}, author = {Yamasaki, T and Aoki, S and Tokita, M}, title = {Allometry and integration do not strongly constrain beak shape evolution in large-billed (Corvus macrorhynchos) and carrion crows (Corvus corone).}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10057-10066}, pmid = {30397447}, issn = {2045-7758}, abstract = {A recent geometric morphometric study on certain landbird lineages revealed that a major part of the variation in beak shape is accounted for by skull size and cranial shape. The study interpreted this result as evidence for the presence of strong evolutionary constraints that severely prevented beak shape from evolving substantially away from predictions of allometry and morphological integration. However, there is another overlooked but similarly plausible explanation for this result: The reason why beak shape does not depart much from predictions might simply be that selection pressures favoring such changes in shape are themselves rare. Here, to evaluate the intensity of evolutionary constraints on avian beak shape more appropriately, we selected large-billed (Corvus macrorhynchos) and carrion crows (Corvus corone) as study objects. These landbird species seem to experience selection pressures favoring a departure from an allometric trajectory. A landmark-based geometric morphometric approach using three-dimensional reconstructions of CT scan images revealed that only 45.4% of the total shape variation was explained by allometry and beak-braincase integration. This suggests that when a selection pressure acts in a different direction to allometry and integration, avian beak shape can react to it and evolve flexibly. As traditionally considered, evolutionary constraints on avian beak shape might not be all that strong.}, } @article {pmid30397446, year = {2018}, author = {Doherty-Bone, TM and Dunn, AM and Brittain, J and Brown, LE}, title = {Invasive alien shredders clear up invasive alien leaf litter.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10049-10056}, pmid = {30397446}, issn = {2045-7758}, abstract = {Biological invasions have the potential to alter ecosystem processes profoundly, but invaders are rarely found alone. Interactions between different invasive alien species, and their cumulative impact on ecosystem functioning, have led to hypotheses of invasion meltdown whereby effects become additive leading to further ecosystem stress. Invasive riparian plants (e.g., Rhododendron ponticum) deposit leaf litter in freshwaters, which may be unconsumed by indigenous species, potentially affecting habitat heterogeneity and flow of energy to the food web. However, invasive alien decapod crustaceans are effective consumers of leaf litter, and it was hypothesized that they would also consume inputs of invasive riparian leaf litter. This study shows that invasive alien signal crayfish (Pacifastacus leniusculus) and Chinese mitten crab (Eriocheir sinensis) effectively break down different types of leaf litter, including invasive alien R. ponticum, at higher rates than indigenous white-clawed crayfish. Secondary products were more varied, with more fine particulate organic matter generated for the less palatable alien leaf litter species. Leaf species caused different changes in body mass of decapods but effects were heterogeneous by leaf and decapod: P. leniusculus showed lower mass loss when consuming R. ponticum while E. sinensis lost mass when consuming A. pseudoplatanus. Impacts of riparian invasions on detritus accumulation in freshwaters are thus potentially buffered by invasive alien decapods, illustrating a need for a more detailed consideration of both positive and negative interspecific feedbacks during biological invasions.}, } @article {pmid30397445, year = {2018}, author = {Lopes, IG and Araújo-Dairiki, TB and Kojima, JT and Val, AL and Portella, MC}, title = {Predicted 2100 climate scenarios affects growth and skeletal development of tambaqui (Colossoma macropomum) larvae.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10039-10048}, pmid = {30397445}, issn = {2045-7758}, abstract = {Climate changes driven by greenhouse gas emissions have been occurring in an accelerated degree, affecting environmental dynamics and living beings. Among all affected biomes, the Amazon is particularly subjected to adverse impacts, such as temperature rises and water acidification. This study aimed to evaluate the impacts of predicted climate change on initial growth and development of an important Amazonian food fish, the tambaqui. We analyzed growth performance, and monitored the initial osteogenic process and the emergence of skeletal anomalies, when larvae were exposed to three climate change scenarios: mild (B1, increase of 1.8°C, 200 ppm of CO2); moderate (A1B, 2.8°C, 400 ppm of CO2); and drastic (A2, 3.4°C, 850 ppm of CO2), in addition to a control room that simulated the current climatic conditions of a pristine tropical forest. The exposure to climate change scenarios (B1, A1B, and A2) resulted in low survival, especially for the animals exposed to A2, (24.7 ± 1.0%). Zootechnical performance under the B1 and A1B scenarios was higher when compared to current and A2, except for condition factor, which was higher in current (2.64 ± 0.09) and A1B (2.41 ± 0.14) scenarios. However, skeletal analysis revealed higher incidences of abnormalities in larvae exposed to A1B (34.82%) and A2 (39.91%) scenarios when compared to current (15.38%). Furthermore, the bone-staining process revealed that after 16 days posthatch (7.8 ± 0.01 mm total length), skeletal structures were still cartilaginous, showing no mineralization in all scenarios. We concluded that tambaqui larvae are well-adapted to high temperatures and may survive mild climate change. However, facing more severe climate conditions, its initial development may be compromised, resulting in high mortality rates and increased incidence of skeletal anomalies, giving evidence that global climate change will hamper tambaqui larvae growth and skeletal ontogeny.}, } @article {pmid30397444, year = {2018}, author = {Ma, ZS}, title = {DAR (diversity-area relationship): Extending classic SAR (species-area relationship) for biodiversity and biogeography analyses.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10023-10038}, pmid = {30397444}, issn = {2045-7758}, abstract = {I extend the classic SAR, which has achieved status of ecological law and plays a critical role in global biodiversity and biogeography analyses, to general DAR (diversity-area relationship). The extension was aimed to remedy a serious application limitation of the traditional SAR that only addressed one aspect of biodiversity scaling-species richness scaling over space, but ignoring species abundance information. The extension was further inspired by a recent consensus that Hill numbers offer the most appropriate measures for alpha-diversity and multiplicative beta-diversity. In particular, Hill numbers are essentially a series of Renyi's entropy values weighted differently along the rare-common-dominant spectrum of species abundance distribution and are in the units of effective number of species (or species equivalents such as OTUs). I therefore postulate that Hill numbers should follow the same or similar law of the traditional SAR. I test the postulation with the American gut microbiome project (AGP) dataset of 1,473 healthy North American individuals. I further propose three new concepts and develop their statistical estimation formulae based on the new DAR extension, including: (i) DAR profile-z-q relationship (DAR scaling parameter z at different diversity order q), (ii) PDO (pair-wise diversity overlap) profile-g-q relationship (PDO parameter g at order q, and (iii) MAD (maximal accrual diversity: Dmax) profile-Dmax-q. While the classic SAR is a special case of our new DAR profile, the PDO and MAD profiles offer novel tools for analyzing biodiversity (including alpha-diversity and beta-diversity) and biogeography over space.}, } @article {pmid30397443, year = {2018}, author = {Martinů, J and Hypša, V and Štefka, J}, title = {Host specificity driving genetic structure and diversity in ectoparasite populations: Coevolutionary patterns in Apodemus mice and their lice.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {10008-10022}, pmid = {30397443}, issn = {2045-7758}, abstract = {A degree of host specificity, manifested by the processes of host-parasite cospeciations and host switches, is assumed to be a major determinant of parasites' evolution. To understand these patterns and formulate appropriate ecological hypotheses, we need better insight into the coevolutionary processes at the intraspecific level, including the maintenance of genetic diversity and population structure of parasites and their hosts. Here, we address these questions by analyzing large-scale molecular data on the louse Polyplax serrata and its hosts, mice of the genus Apodemus, across a broad range of European localities. Using mitochondrial DNA sequences and microsatellite data, we demonstrate the general genetic correspondence of the Apodemus/Polyplax system to the scenario of the postglacial recolonization of Europe, but we also show several striking discrepancies. Among the most interesting are the evolution of different degrees of host specificity in closely related louse lineages in sympatry, or decoupled population structures of the host and parasites in central Europe. We also find strong support for the prediction that parasites with narrower host specificity possess a lower level of genetic diversity and a deeper pattern of interpopulation structure as a result of limited dispersal and smaller effective population size.}, } @article {pmid30397442, year = {2018}, author = {Zheng, J and She, W and Zhang, Y and Bai, Y and Qin, S and Wu, B}, title = {Nitrogen enrichment alters nutrient resorption and exacerbates phosphorus limitation in the desert shrub Artemisia ordosica.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {9998-10007}, pmid = {30397442}, issn = {2045-7758}, abstract = {Increasing nitrogen (N) deposition and precipitation are major drivers of global changes that are expected to influence plant nutrient resorption in desert ecosystems, where plant growth is often nutrient and water limited. However, knowledge on the effects of increased N and precipitation on them remain poorly understood. This study determined the effects of increased N (ambient, 60 kg N ha-1 year-1) and water supply (ambient, +20%, +40%), and their combination on the leaf nutrient resorption of Artemisia ordosica, a dominant shrub in the Mu Us Desert of northern China. After 2 years of treatments, only N addition significantly decreased the N resorption efficiency of A. ordosica. Both N and water addition had no effect on the phosphorus (P) resorption efficiency of this shrub, and there were no interactive effects of N and water availability on shrub nutrient resorption. The responses of shrub leaf N:P ratio tended to saturate as soil available N:P increased. The aboveground net primary productivity of A. ordosica was positively correlated with leaf P resorption efficiency, rather than N resorption efficiency. Our results suggest that N addition exacerbated the P limitation of the shrub growth and played a more fundamental role than water addition in controlling the nutrient resorption process of the desert shrub A. ordosica. This information contributes to understand the relationship between nutrient conservation strategy and plant growth of desert shrub species under global environmental changes.}, } @article {pmid30397441, year = {2018}, author = {Gopko, M and Chowdhury, MMR and Taskinen, J}, title = {Interactions between two parasites of brown trout (Salmo trutta): Consequences of preinfection.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {9986-9997}, pmid = {30397441}, issn = {2045-7758}, abstract = {Preinfection by one parasitic species may facilitate or by contrast hamper the subsequent penetration and/or establishment of other parasites in a host. The biology of interacting species, timing of preinfection, and dosage of subsequent parasite exposure are likely important variables in this multiparasite dynamic infection process. The increased vulnerability to subsequent infection can be an important and often overlooked factor influencing parasite virulence. We investigated how the preinfection by freshwater pearl mussel Margaritifera margaritifera glochidia could influence the success of subsequent infection by the common trematode Diplostomum pseudospathaceum in brown trout Salmo trutta and vice versa whether preinfection by the trematode made fish more susceptible to glochidia infection. The first experiment was repeated twice with different (low and high) exposure doses to initiate the subsequent trematode infection, while in the second experiment we varied the timing of the preinfection with trematodes. The preinfection with glochidia made fish more vulnerable to subsequent infection with trematodes. Since the trematodes penetrate through the gills, we suggest that increased host vulnerability was most likely the result of increased respiration caused by the freshwater pearl mussel glochidia encysted on gills. In turn, brown trout preinfected with trematodes were more vulnerable to the subsequent glochidial infection, but only if they were preinfected shortly before the subsequent infection (20 hr). Fish preinfected with trematodes earlier (2 weeks before the subsequent infection) did not differ in their vulnerability to glochidia. These effects were observed at moderate intensities of infections similar to those that occur in nature. Our study demonstrates how the timing and sequence of exposure to parasitic species can influence infection success in a host-multiparasite system. It indicates that the negative influence of glochidia on host fitness is likely to be underestimated and that this should be taken into consideration when organizing freshwater pearl mussel restoration procedures.}, } @article {pmid30397440, year = {2018}, author = {Sun, YX and Hao, YN and Yan, Y and Zhang, Y and Feng, Y and Liu, TX}, title = {Morphological and biological characterization of a light-colored mutant in the multicolored Asian lady beetle, Harmonia axyridis.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {9975-9985}, pmid = {30397440}, issn = {2045-7758}, abstract = {Insect cuticle color formed with melanin pigments has numerous types of mutants which usually cause pleiotropic effects. Melanism has been widely studied, but mutants with light-colored phenotype as well as the consequent fitness changes have rarely been reported.Here, in the laboratory strain of Harmonia axyridis, we found a novel mutant gr and confirmed that the mutation was inherited in a simple Mendelian autosomal recessive manner. This mutant (HAM) continuously displayed a light-colored pigmentation versus dark blackish in the wild phenotype (HAW). L-DOPA and dopamine are melanin precursors, and less L-DOPA was present in the cuticle of larval and adult HAM mutants compared to HAW wild type, but more dopamine was detected in the larval cuticle of HAM (p ≤ 0.0235). For the orange background of elytra, the composition as well as total concentration of carotenoids was different between HAM and HAW, which resulted in significantly lower saturation value but significantly higher hue value in HAM than in HAW (p < 0.0001).Extensive fitness changes were detected in HAM. (a) HAM larvae had similar predation capacity and preimaginal development time as HAW, but the newly emerged adults were much smaller (p < 0.0001). (b) Both fecundity and egg hatch rate in cross ♀(HAM) × ♂(HAM) were significantly lower than those in ♀(HAW) × ♂(HAW) (p ≤ 0.0087), but were not different with those in ♀(HAW) × ♂(HAM).}, } @article {pmid30397439, year = {2018}, author = {Hund, AK and Churchill, AC and Faist, AM and Havrilla, CA and Love Stowell, SM and McCreery, HF and Ng, J and Pinzone, CA and Scordato, ESC}, title = {Transforming mentorship in STEM by training scientists to be better leaders.}, journal = {Ecology and evolution}, volume = {8}, number = {20}, pages = {9962-9974}, pmid = {30397439}, issn = {2045-7758}, abstract = {Effective mentoring is a key component of academic and career success that contributes to overall measures of productivity. Mentoring relationships also play an important role in mental health and in recruiting and retaining students from groups underrepresented in STEM fields. Despite these clear and measurable benefits, faculty generally do not receive mentorship training, and feedback mechanisms and assessment to improve mentoring in academia are limited. Ineffective mentoring can negatively impact students, faculty, departments, and institutions via decreased productivity, increased stress, and the loss of valuable research products and talented personnel. Thus, there are clear incentives to invest in and implement formal training to improve mentorship in STEM fields. Here, we outline the unique challenges of mentoring in academia and present results from a survey of STEM scientists that support both the need and desire for more formal mentorship training. Using survey results and the primary literature, we identify common behaviors of effective mentors and outline a set of mentorship best practices. We argue that these best practices, as well as the key qualities of flexibility, communication, and trust, are skills that can be taught to prospective and current faculty. We present a model and resources for mentorship training based on our research, which we successfully implemented at the University of Colorado, Boulder, with graduate students and postdocs. We conclude that such training is an important and cost-effective step toward improving mentorship in STEM fields.}, } @article {pmid30397352, year = {2018}, author = {Lockyer, NS}, title = {Leon Lederman (1922-2018).}, journal = {Nature}, volume = {563}, number = {7730}, pages = {185}, doi = {10.1038/d41586-018-07295-z}, pmid = {30397352}, issn = {1476-4687}, } @article {pmid30397347, year = {2018}, author = {Da Mesquita, S and Louveau, A and Vaccari, A and Smirnov, I and Cornelison, RC and Kingsmore, KM and Contarino, C and Onengut-Gumuscu, S and Farber, E and Raper, D and Viar, KE and Powell, RD and Baker, W and Dabhi, N and Bai, R and Cao, R and Hu, S and Rich, SS and Munson, JM and Lopes, MB and Overall, CC and Acton, ST and Kipnis, J}, title = {Publisher Correction: Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {E7}, doi = {10.1038/s41586-018-0689-7}, pmid = {30397347}, issn = {1476-4687}, abstract = {Change history: In this Article, Extended Data Fig. 9 was appearing as Fig. 2 in the HTML, and in Fig. 2, the panel labels 'n' and 'o' overlapped the figure; these errors have been corrected online.}, } @article {pmid30397346, year = {2018}, author = {Borducchi, EN and Liu, J and Nkolola, JP and Cadena, AM and Yu, WH and Fischinger, S and Broge, T and Abbink, P and Mercado, NB and Chandrashekar, A and Jetton, D and Peter, L and McMahan, K and Moseley, ET and Bekerman, E and Hesselgesser, J and Li, W and Lewis, MG and Alter, G and Geleziunas, R and Barouch, DH}, title = {Publisher Correction: Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {E8}, doi = {10.1038/s41586-018-0721-y}, pmid = {30397346}, issn = {1476-4687}, abstract = {In Fig. 4b of this Article, the x-axis labels 'PGT121' and 'GS-9620' were inadvertently swapped in both graphs. In Fig. 5a, b, 'TLR7' should have been 'GS-9620'. These figures have been corrected online.}, } @article {pmid30397345, year = {2018}, author = {Negnevitsky, V and Marinelli, M and Mehta, KK and Lo, HY and Flühmann, C and Home, JP}, title = {Repeated multi-qubit readout and feedback with a mixed-species trapped-ion register.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {527-531}, doi = {10.1038/s41586-018-0668-z}, pmid = {30397345}, issn = {1476-4687}, abstract = {Quantum error correction is essential for realizing the full potential of large-scale quantum information processing devices1,2. Fundamental to its experimental realization is the repetitive detection of errors via projective measurements of quantum correlations among qubits, as well as corrections using conditional feedback3. Repetitive application of such tasks requires that they neither induce unwanted crosstalk nor impede further control operations, which is challenging owing to the need to dissipatively couple qubits to the classical world for detection and reinitialization. For trapped ions, state readout involves scattering large numbers of resonant photons, which increases the probability of stray light causing errors on nearby qubits and leads to undesirable recoil heating of the ion motion. Here we demonstrate up to 50 sequential measurements of correlations between two beryllium ion microwave qubits using an ancillary optical qubit in a calcium ion, and implement feedback that allows us to stabilize two-qubit subspaces as well as Bell states, a class of maximally entangled states. Multi-qubit mixed-species gates are used to transfer information within the register from the qubit to the ancilla, enabling readout with negligible crosstalk to the data qubits. Heating of the ion motion during detection is mitigated by recooling all three ions using light that interacts with only the calcium ion, known as sympathetic cooling. A key element of our experimental setup is a powerful classical control system that features flexible in-sequence processing for feedback control. The methods employed here provide essential tools for scaling trapped-ion quantum computing, quantum-state control and entanglement-enhanced quantum metrology4.}, } @article {pmid30397344, year = {2018}, author = {Kasahara, K and Krautkramer, KA and Org, E and Romano, KA and Kerby, RL and Vivas, EI and Mehrabian, M and Denu, JM and Bäckhed, F and Lusis, AJ and Rey, FE}, title = {Interactions between Roseburia intestinalis and diet modulate atherogenesis in a murine model.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1461-1471}, pmid = {30397344}, issn = {2058-5276}, support = {F30 DK108494/DK/NIDDK NIH HHS/United States ; P01 HL030568/HL/NHLBI NIH HHS/United States ; R01 DK108259/DK/NIDDK NIH HHS/United States ; T32 GM008692/GM/NIGMS NIH HHS/United States ; }, abstract = {Humans with metabolic and inflammatory diseases frequently harbour lower levels of butyrate-producing bacteria in their gut. However, it is not known whether variation in the levels of these organisms is causally linked with disease development and whether diet modifies the impact of these bacteria on health. Here we show that a prominent gut-associated butyrate-producing bacterial genus (Roseburia) is inversely correlated with atherosclerotic lesion development in a genetically diverse mouse population. We use germ-free apolipoprotein E-deficient mice colonized with synthetic microbial communities that differ in their capacity to generate butyrate to demonstrate that Roseburia intestinalis interacts with dietary plant polysaccharides to: impact gene expression in the intestine, directing metabolism away from glycolysis and toward fatty acid utilization; lower systemic inflammation; and ameliorate atherosclerosis. Furthermore, intestinal administration of butyrate reduces endotoxaemia and atherosclerosis development. Together, our results illustrate how modifiable diet-by-microbiota interactions impact cardiovascular disease, and suggest that interventions aimed at increasing the representation of butyrate-producing bacteria may provide protection against atherosclerosis.}, } @article {pmid30397343, year = {2019}, author = {Özcan, A and Pausch, P and Linden, A and Wulf, A and Schühle, K and Heider, J and Urlaub, H and Heimerl, T and Bange, G and Randau, L}, title = {Type IV CRISPR RNA processing and effector complex formation in Aromatoleum aromaticum.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {89-96}, doi = {10.1038/s41564-018-0274-8}, pmid = {30397343}, issn = {2058-5276}, abstract = {Type IV CRISPR-Cas modules belong to class 1 prokaryotic adaptive immune systems, which are defined by the presence of multisubunit effector complexes. They usually lack the known Cas proteins involved in adaptation and target cleavage, and their function has not been experimentally addressed. To investigate RNA and protein components of this CRISPR-Cas type, we located a complete type IV cas gene locus and an adjacent CRISPR array on a megaplasmid of Aromatoleum aromaticum EbN1, which contains an additional type I-C system on its chromosome. RNA sequencing analyses verified CRISPR RNA (crRNA) production and maturation for both systems. Type IV crRNAs were shown to harbour unusually short 7 nucleotide 5'-repeat tags and stable 3' hairpin structures. A unique Cas6 variant (Csf5) was identified that generates crRNAs that are specifically incorporated into type IV CRISPR-ribonucleoprotein (crRNP) complexes. Structures of RNA-bound Csf5 were obtained. Recombinant production and purification of the type IV Cas proteins, together with electron microscopy, revealed that Csf2 acts as a helical backbone for type IV crRNPs that include Csf5, Csf3 and a large subunit (Csf1). Mass spectrometry analyses identified protein-protein and protein-RNA contact sites. These results highlight evolutionary connections between type IV and type I CRISPR-Cas systems and demonstrate that type IV CRISPR-Cas systems employ crRNA-guided effector complexes.}, } @article {pmid30397342, year = {2019}, author = {Sorensen, JW and Dunivin, TK and Tobin, TC and Shade, A}, title = {Ecological selection for small microbial genomes along a temperate-to-thermal soil gradient.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {55-61}, doi = {10.1038/s41564-018-0276-6}, pmid = {30397342}, issn = {2058-5276}, abstract = {Small bacterial and archaeal genomes provide insights into the minimal requirements for life1 and are phylogenetically widespread2. However, the precise environmental pressures that constrain genome size in free-living microorganisms are unknown. A study including isolates has shown that thermophiles and other bacteria with high optimum growth temperatures often have small genomes3. It is unclear whether this relationship extends generally to microorganisms in nature4,5 and more specifically to microorganisms that inhabit complex and highly variable environments, such as soils3,6,7. To understand the genomic traits of thermally adapted microorganisms, here we investigated metagenomes from a 45 °C gradient of temperate-to-thermal soils that lie over the ongoing Centralia, Pennsylvania (USA) coal-seam fire. We found that hot soils harboured distinct communities with small genomes and small cell sizes relative to those in ambient soils. Hot soils notably lacked genes that encode known two-component regulatory systems, and antimicrobial production and resistance genes. Our results provide field evidence for the inverse relationship between microbial genome size and temperature in a diverse, free-living community over a wide range of temperatures that support microbial life.}, } @article {pmid30397341, year = {2019}, author = {Zheng, Q and Zhu, R and Xu, L and He, M and Yan, X and Liu, D and Yin, Z and Wu, Y and Li, Y and Yang, L and Hou, W and Li, S and Li, Z and Chen, Z and Li, Z and Yu, H and Gu, Y and Zhang, J and Baker, TS and Zhou, ZH and Graham, BS and Cheng, T and Li, S and Xia, N}, title = {Atomic structures of enterovirus D68 in complex with two monoclonal antibodies define distinct mechanisms of viral neutralization.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {124-133}, doi = {10.1038/s41564-018-0275-7}, pmid = {30397341}, issn = {2058-5276}, abstract = {Enterovirus D68 (EV-D68) undergoes structural transformation between mature, cell-entry intermediate (A-particle) and empty forms throughout its life cycle. Structural information for the various forms and antibody-bound capsids will facilitate the development of effective vaccines and therapeutics against EV-D68 infection, which causes childhood respiratory and paralytic diseases worldwide. Here, we report the structures of three EV-D68 capsid states representing the virus at major phases. We further describe two original monoclonal antibodies (15C5 and 11G1) with distinct structurally defined mechanisms for virus neutralization. 15C5 and 11G1 engage the capsid loci at icosahedral three-fold and five-fold axes, respectively. To block viral attachment, 15C5 binds three forms of capsids, and triggers mature virions to transform into A-particles, mimicking engagement by the functional receptor ICAM-5, whereas 11G1 exclusively recognizes the A-particle. Our data provide a structural and molecular explanation for the transition of picornavirus capsid conformations and demonstrate distinct mechanisms for antibody-mediated neutralization.}, } @article {pmid30397340, year = {2018}, author = {Pruneda, JN and Bastidas, RJ and Bertsoulaki, E and Swatek, KN and Santhanam, B and Clague, MJ and Valdivia, RH and Urbé, S and Komander, D}, title = {A Chlamydia effector combining deubiquitination and acetylation activities induces Golgi fragmentation.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1377-1384}, doi = {10.1038/s41564-018-0271-y}, pmid = {30397340}, issn = {2058-5276}, support = {R01 AI100759/AI/NIAID NIH HHS/United States ; U19 AI084044/AI/NIAID NIH HHS/United States ; }, abstract = {Pathogenic bacteria are armed with potent effector proteins that subvert host signalling processes during infection1. The activities of bacterial effectors and their associated roles within the host cell are often poorly understood, particularly for Chlamydia trachomatis2, a World Health Organization designated neglected disease pathogen. We identify and explain remarkable dual Lys63-deubiquitinase (DUB) and Lys-acetyltransferase activities in the Chlamydia effector ChlaDUB1. Crystal structures capturing intermediate stages of each reaction reveal how the same catalytic centre of ChlaDUB1 can facilitate such distinct processes, and enable the generation of mutations that uncouple the two activities. Targeted Chlamydia mutant strains allow us to link the DUB activity of ChlaDUB1 and the related, dedicated DUB ChlaDUB2 to fragmentation of the host Golgi apparatus, a key process in Chlamydia infection for which effectors have remained elusive. Our work illustrates the incredible versatility of bacterial effector proteins, and provides important insights towards understanding Chlamydia pathogenesis.}, } @article {pmid30397339, year = {2018}, author = {Cousminer, DL and Grant, SFA}, title = {Author Correction: Public resources aid diabetes gene discovery.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1753}, doi = {10.1038/s41588-018-0292-8}, pmid = {30397339}, issn = {1546-1718}, abstract = {In the version of this article originally published, the text was incorrect in the first paragraph of the 'Remaining challenges' section. The first two sentences appeared as "Even though this current study substantially increases the number of loci associated with T2D, only approximately 18% of the genetic component of T2D risk is explained by the total complement of genetic variants uncovered genome wide in Mahajan et al.6. Interestingly, only a small proportion of that heritability was explained by low-frequency or rare variants (~1.1%), thus potentially indicating that many more of these variants still remain to be characterized in even larger sample sizes." However, they should have read "Even though this current study substantially increases the number of loci associated with T2D, only a proportion of the genetic component of T2D risk is explained by the total complement of genetic variants uncovered genome wide in Mahajan et al.6. Interestingly, only a relatively small proportion of that heritability was explained by low-frequency or rare variants, thus potentially indicating that many more of these variants still remain to be characterized in even larger sample sizes." The text has been corrected in the HTML and PDF versions of the paper.}, } @article {pmid30397338, year = {2018}, author = {Jónsson, H and Sulem, P and Arnadottir, GA and Pálsson, G and Eggertsson, HP and Kristmundsdottir, S and Zink, F and Kehr, B and Hjorleifsson, KE and Jensson, BÖ and Jonsdottir, I and Marelsson, SE and Gudjonsson, SA and Gylfason, A and Jonasdottir, A and Jonasdottir, A and Stacey, SN and Magnusson, OT and Thorsteinsdottir, U and Masson, G and Kong, A and Halldorsson, BV and Helgason, A and Gudbjartsson, DF and Stefansson, K}, title = {Multiple transmissions of de novo mutations in families.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1674-1680}, doi = {10.1038/s41588-018-0259-9}, pmid = {30397338}, issn = {1546-1718}, abstract = {De novo mutations (DNMs) cause a large proportion of severe rare diseases of childhood. DNMs that occur early may result in mosaicism of both somatic and germ cells. Such early mutations can cause recurrence of disease. We scanned 1,007 sibling pairs from 251 families and identified 878 DNMs shared by siblings (ssDNMs) at 448 genomic sites. We estimated DNM recurrence probability based on parental mosaicism, sharing of DNMs among siblings, parent-of-origin, mutation type and genomic position. We detected 57.2% of ssDNMs in the parental blood. The recurrence probability of a DNM decreases by 2.27% per year for paternal DNMs and 1.78% per year for maternal DNMs. Maternal ssDNMs are more likely to be T>C mutations than paternal ssDNMs, and less likely to be C>T mutations. Depending on the properties of the DNM, the recurrence probability ranges from 0.011% to 28.5%. We have launched an online calculator to allow estimation of DNM recurrence probability for research purposes.}, } @article {pmid30397337, year = {2018}, author = {Ainscough, BJ and Barnell, EK and Ronning, P and Campbell, KM and Wagner, AH and Fehniger, TA and Dunn, GP and Uppaluri, R and Govindan, R and Rohan, TE and Griffith, M and Mardis, ER and Swamidass, SJ and Griffith, OL}, title = {A deep learning approach to automate refinement of somatic variant calling from cancer sequencing data.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1735-1743}, doi = {10.1038/s41588-018-0257-y}, pmid = {30397337}, issn = {1546-1718}, abstract = {Cancer genomic analysis requires accurate identification of somatic variants in sequencing data. Manual review to refine somatic variant calls is required as a final step after automated processing. However, manual variant refinement is time-consuming, costly, poorly standardized, and non-reproducible. Here, we systematized and standardized somatic variant refinement using a machine learning approach. The final model incorporates 41,000 variants from 440 sequencing cases. This model accurately recapitulated manual refinement labels for three independent testing sets (13,579 variants) and accurately predicted somatic variants confirmed by orthogonal validation sequencing data (212,158 variants). The model improves on manual somatic refinement by reducing bias on calls otherwise subject to high inter-reviewer variability.}, } @article {pmid30397336, year = {2018}, author = {Haney, MS and Bohlen, CJ and Morgens, DW and Ousey, JA and Barkal, AA and Tsui, CK and Ego, BK and Levin, R and Kamber, RA and Collins, H and Tucker, A and Li, A and Vorselen, D and Labitigan, L and Crane, E and Boyle, E and Jiang, L and Chan, J and Rincón, E and Greenleaf, WJ and Li, B and Snyder, MP and Weissman, IL and Theriot, JA and Collins, SR and Barres, BA and Bassik, MC}, title = {Identification of phagocytosis regulators using magnetic genome-wide CRISPR screens.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1716-1727}, doi = {10.1038/s41588-018-0254-1}, pmid = {30397336}, issn = {1546-1718}, abstract = {Phagocytosis is required for a broad range of physiological functions, from pathogen defense to tissue homeostasis, but the mechanisms required for phagocytosis of diverse substrates remain incompletely understood. Here, we developed a rapid magnet-based phenotypic screening strategy, and performed eight genome-wide CRISPR screens in human cells to identify genes regulating phagocytosis of distinct substrates. After validating select hits in focused miniscreens, orthogonal assays and primary human macrophages, we show that (1) the previously uncharacterized gene NHLRC2 is a central player in phagocytosis, regulating RhoA-Rac1 signaling cascades that control actin polymerization and filopodia formation, (2) very-long-chain fatty acids are essential for efficient phagocytosis of certain substrates and (3) the previously uncharacterized Alzheimer's disease-associated gene TM2D3 can preferentially influence uptake of amyloid-β aggregates. These findings illuminate new regulators and core principles of phagocytosis, and more generally establish an efficient method for unbiased identification of cellular uptake mechanisms across diverse physiological and pathological contexts.}, } @article {pmid30397335, year = {2018}, author = {Pattison, JM and Melo, SP and Piekos, SN and Torkelson, JL and Bashkirova, E and Mumbach, MR and Rajasingh, C and Zhen, HH and Li, L and Liaw, E and Alber, D and Rubin, AJ and Shankar, G and Bao, X and Chang, HY and Khavari, PA and Oro, AE}, title = {Retinoic acid and BMP4 cooperate with p63 to alter chromatin dynamics during surface epithelial commitment.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1658-1665}, pmid = {30397335}, issn = {1546-1718}, support = {F32 AR070565/AR/NIAMS NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 AR045192/AR/NIAMS NIH HHS/United States ; }, abstract = {Human embryonic stem cell (hESC) differentiation promises advances in regenerative medicine1-3, yet conversion of hESCs into transplantable cells or tissues remains poorly understood. Using our keratinocyte differentiation system, we employ a multi-dimensional genomics approach to interrogate the contributions of inductive morphogens retinoic acid and bone morphogenetic protein 4 (BMP4) and the epidermal master regulator p63 (encoded by TP63)4,5 during surface ectoderm commitment. In contrast to other master regulators6-9, p63 effects major transcriptional changes only after morphogens alter chromatin accessibility, establishing an epigenetic landscape for p63 to modify. p63 distally closes chromatin accessibility and promotes accumulation of H3K27me3 (trimethylated histone H3 lysine 27). Cohesin HiChIP10 visualizations of chromosome conformation show that p63 and the morphogens contribute to dynamic long-range chromatin interactions, as illustrated by TFAP2C regulation11. Our study demonstrates the unexpected dependency of p63 on morphogenetic signaling and provides novel insights into how a master regulator can specify diverse transcriptional programs based on the chromatin landscape induced by exposure to specific morphogens.}, } @article {pmid30397334, year = {2018}, author = {Bai, H and Guo, X and Narisu, N and Lan, T and Wu, Q and Xing, Y and Zhang, Y and Bond, SR and Pei, Z and Zhang, Y and Zhang, D and Jirimutu, J and Zhang, D and Yang, X and Morigenbatu, M and Zhang, L and Ding, B and Guan, B and Cao, J and Lu, H and Liu, Y and Li, W and Dang, N and Jiang, M and Wang, S and Xu, H and Wang, D and Liu, C and Luo, X and Gao, Y and Li, X and Wu, Z and Yang, L and Meng, F and Ning, X and Hashenqimuge, H and Wu, K and Wang, B and Suyalatu, S and Liu, Y and Ye, C and Wu, H and Leppälä, K and Li, L and Fang, L and Chen, Y and Xu, W and Li, T and Liu, X and Xu, X and Gignoux, CR and Yang, H and Brody, LC and Wang, J and Kristiansen, K and Burenbatu, B and Zhou, H and Yin, Y}, title = {Whole-genome sequencing of 175 Mongolians uncovers population-specific genetic architecture and gene flow throughout North and East Asia.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1696-1704}, doi = {10.1038/s41588-018-0250-5}, pmid = {30397334}, issn = {1546-1718}, abstract = {The genetic variation in Northern Asian populations is currently undersampled. To address this, we generated a new genetic variation reference panel by whole-genome sequencing of 175 ethnic Mongolians, representing six tribes. The cataloged variation in the panel shows strong population stratification among these tribes, which correlates with the diverse demographic histories in the region. Incorporating our results with the 1000 Genomes Project panel identifies derived alleles shared between Finns and Mongolians/Siberians, suggesting that substantial gene flow between northern Eurasian populations has occurred in the past. Furthermore, we highlight that North, East, and Southeast Asian populations are more aligned with each other than these groups are with South Asian and Oceanian populations.}, } @article {pmid30397333, year = {2019}, author = {, }, title = {Comparative genomics of the major parasitic worms.}, journal = {Nature genetics}, volume = {51}, number = {1}, pages = {163-174}, doi = {10.1038/s41588-018-0262-1}, pmid = {30397333}, issn = {1546-1718}, support = {R21 AI126466/AI/NIAID NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R01 AI081803/AI/NIAID NIH HHS/United States ; R01 GM097435/GM/NIGMS NIH HHS/United States ; }, abstract = {Parasitic nematodes (roundworms) and platyhelminths (flatworms) cause debilitating chronic infections of humans and animals, decimate crop production and are a major impediment to socioeconomic development. Here we report a broad comparative study of 81 genomes of parasitic and non-parasitic worms. We have identified gene family births and hundreds of expanded gene families at key nodes in the phylogeny that are relevant to parasitism. Examples include gene families that modulate host immune responses, enable parasite migration though host tissues or allow the parasite to feed. We reveal extensive lineage-specific differences in core metabolism and protein families historically targeted for drug development. From an in silico screen, we have identified and prioritized new potential drug targets and compounds for testing. This comparative genomics resource provides a much-needed boost for the research community to understand and combat parasitic worms.}, } @article {pmid30397305, year = {2018}, author = {Mommer, L and van Ruijven, J}, title = {Focus on a locus.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1838-1839}, doi = {10.1038/s41559-018-0736-7}, pmid = {30397305}, issn = {2397-334X}, } @article {pmid30397304, year = {2018}, author = {Thaker, M and Zambre, A and Bhosale, H}, title = {Wind farms have cascading impacts on ecosystems across trophic levels.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1854-1858}, doi = {10.1038/s41559-018-0707-z}, pmid = {30397304}, issn = {2397-334X}, abstract = {Wind farms are a cleaner alternative to fossil fuels for mitigating the effects of climate change, but they also have complex ecological consequences. In the biodiversity hotspot of the Western Ghats in India, we find that wind farms reduce the abundance and activity of predatory birds (for example, Buteo, Butastur and Elanus species), which consequently increases the density of lizards, Sarada superba. The cascading effects of wind turbines on lizards include changes in behaviour, physiology and morphology that reflect a combination of predator release and density-dependent competition. By adding an effective trophic level to the top of food webs, we find that wind farms have emerging impacts that are greatly underestimated. There is thus a strong need for an ecosystem-wide view when aligning green-energy goals with environment protection.}, } @article {pmid30397303, year = {2018}, author = {Wuest, SE and Niklaus, PA}, title = {A plant biodiversity effect resolved to a single chromosomal region.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1933-1939}, pmid = {30397303}, issn = {2397-334X}, abstract = {Despite extensive evidence that biodiversity promotes plant community productivity, progress towards understanding the mechanistic basis of this effect remains slow, impeding the development of predictive ecological theory and agricultural applications. Here, we analysed non-additive interactions between genetically divergent Arabidopsis accessions in experimental plant communities. By combining methods from ecology and quantitative genetics, we identify a major effect locus at which allelic differences between individuals increase the above-ground productivity of communities. In experiments with near-isogenic lines, we show that this diversity effect acts independently of other genomic regions and can be resolved to a single region representing less than 0.3% of the genome. Using plant-soil feedback experiments, we also demonstrate that allelic diversity causes genotype-specific soil legacy responses in a consecutive growing period, even after the original community has disappeared. Our work thus suggests that positive diversity effects can be linked to single Mendelian factors, and that a range of complex community properties can have a simple cause. This may pave the way to novel breeding strategies, focusing on phenotypic properties that manifest themselves beyond isolated individuals; that is, at a higher level of biological organization.}, } @article {pmid30397302, year = {2018}, author = {Smith, AMS and Kolden, CA and Bowman, DMJS}, title = {Biomimicry can help humans to coexist sustainably with fire.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1827-1829}, doi = {10.1038/s41559-018-0712-2}, pmid = {30397302}, issn = {2397-334X}, } @article {pmid30397301, year = {2018}, author = {Smith, JR and Letten, AD and Ke, PJ and Anderson, CB and Hendershot, JN and Dhami, MK and Dlott, GA and Grainger, TN and Howard, ME and Morrison, BML and Routh, D and San Juan, PA and Mooney, HA and Mordecai, EA and Crowther, TW and Daily, GC}, title = {A global test of ecoregions.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1889-1896}, doi = {10.1038/s41559-018-0709-x}, pmid = {30397301}, issn = {2397-334X}, abstract = {A foundational paradigm in biological and Earth sciences is that our planet is divided into distinct ecoregions and biomes demarking unique assemblages of species. This notion has profoundly influenced scientific research and environmental policy. Given recent advances in technology and data availability, however, we are now poised to ask whether ecoregions meaningfully delimit biological communities. Using over 200 million observations of plants, animals and fungi we show compelling evidence that ecoregions delineate terrestrial biodiversity patterns. We achieve this by testing two competing hypotheses: the sharp-transition hypothesis, positing that ecoregion borders divide differentiated biotic communities; and the gradual-transition hypothesis, proposing instead that species turnover is continuous and largely independent of ecoregion borders. We find strong support for the sharp-transition hypothesis across all taxa, although adherence to ecoregion boundaries varies across taxa. Although plant and vertebrate species are tightly linked to sharp ecoregion boundaries, arthropods and fungi show weaker affiliations to this set of ecoregion borders. Our results highlight the essential value of ecological data for setting conservation priorities and reinforce the importance of protecting habitats across as many ecoregions as possible. Specifically, we conclude that ecoregion-based conservation planning can guide investments that simultaneously protect species-, community- and ecosystem-level biodiversity, key for securing Earth's life support systems into the future.}, } @article {pmid30397300, year = {2018}, author = {Liu, Q and Ma, A and Wei, L and Pang, Y and Wu, B and Luo, T and Zhou, Y and Zheng, HX and Jiang, Q and Gan, M and Zuo, T and Liu, M and Yang, C and Jin, L and Comas, I and Gagneux, S and Zhao, Y and Pepperell, CS and Gao, Q}, title = {China's tuberculosis epidemic stems from historical expansion of four strains of Mycobacterium tuberculosis.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1982-1992}, doi = {10.1038/s41559-018-0680-6}, pmid = {30397300}, issn = {2397-334X}, support = {638553//European Research Council/International ; R01 AI113287/AI/NIAID NIH HHS/United States ; }, abstract = {A small number of high-burden countries account for the majority of tuberculosis cases worldwide. Detailed data are lacking from these regions. To explore the evolutionary history of Mycobacterium tuberculosis in China-the country with the third highest tuberculosis burden-we analysed a countrywide collection of 4,578 isolates. Little genetic diversity was detected, with 99.4% of the bacterial population belonging to lineage 2 and three sublineages of lineage 4. The deeply rooted phylogenetic positions and geographic restriction of these four genotypes indicate that their populations expanded in situ following a small number of introductions to China. Coalescent analyses suggest that these bacterial subpopulations emerged in China around 1,000 years ago, and expanded in parallel from the twelfth century onwards, and that the whole population peaked in the late eighteenth century. More recently, sublineage L2.3, which is indigenous to China and exhibited relatively high transmissibility and extensive global dissemination, came to dominate the population dynamics of M. tuberculosis in China. Our results indicate that historical expansion of four M. tuberculosis strains shaped the current tuberculosis epidemic in China, and highlight the long-term genetic continuity of the indigenous M. tuberculosis population.}, } @article {pmid30397299, year = {2018}, author = {Siqueira, T and Wunderlich, A}, title = {Dispersal dilemmas.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1836-1837}, doi = {10.1038/s41559-018-0720-2}, pmid = {30397299}, issn = {2397-334X}, } @article {pmid30397298, year = {2018}, author = {Fronhofer, EA and Legrand, D and Altermatt, F and Ansart, A and Blanchet, S and Bonte, D and Chaine, A and Dahirel, M and De Laender, F and De Raedt, J and di Gesu, L and Jacob, S and Kaltz, O and Laurent, E and Little, CJ and Madec, L and Manzi, F and Masier, S and Pellerin, F and Pennekamp, F and Schtickzelle, N and Therry, L and Vong, A and Winandy, L and Cote, J}, title = {Bottom-up and top-down control of dispersal across major organismal groups.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1859-1863}, doi = {10.1038/s41559-018-0686-0}, pmid = {30397298}, issn = {2397-334X}, abstract = {Ecology and evolution unfold in spatially structured communities, where dispersal links dynamics across scales. Because dispersal is multicausal, identifying general drivers remains challenging. In a coordinated distributed experiment spanning organisms from protozoa to vertebrates, we tested whether two fundamental determinants of local dynamics, top-down and bottom-up control, generally explain active dispersal. We show that both factors consistently increased emigration rates and use metacommunity modelling to highlight consequences on local and regional dynamics.}, } @article {pmid30397154, year = {2018}, author = {Jin, I and Udo, H and Nicholls, R and Zhu, H and Kandel, ER and Hawkins, RD}, title = {Autocrine signaling by an Aplysia neurotrophin forms a presynaptic positive feedback loop.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11168-E11177}, pmid = {30397154}, issn = {1091-6490}, support = {//Howard Hughes Medical Institute/International ; }, mesh = {Animals ; Aplysia/*physiology ; Autocrine Communication/*physiology ; Cyclic AMP-Dependent Protein Kinases/*metabolism ; Excitatory Postsynaptic Potentials/physiology ; Long-Term Potentiation/physiology ; Motor Neurons/physiology ; Nerve Growth Factors/*metabolism ; Neuronal Plasticity/physiology ; Presynaptic Terminals/physiology ; Receptor Protein-Tyrosine Kinases/*metabolism ; Sensory Receptor Cells/physiology ; Serotonin/metabolism ; Serotonin Plasma Membrane Transport Proteins/metabolism ; Signal Transduction/physiology ; Synapses/*physiology ; }, abstract = {Whereas short-term plasticity is often initiated on one side of the synapse, long-term plasticity involves coordinated changes on both sides, implying extracellular signaling. We have investigated the possible signaling role of an Aplysia neurotrophin (ApNT) in facilitation induced by serotonin (5HT) at sensory-to-motor neuron synapses in culture. ApNT is an ortholog of mammalian BDNF, which has been reported to act as either an anterograde, retrograde, or autocrine signal, so that its pre- and postsynaptic sources and targets remain unclear. We now report that ApNT acts as a presynaptic autocrine signal that forms part of a positive feedback loop with ApTrk and PKA. That loop stimulates spontaneous transmitter release, which recruits postsynaptic mechanisms, and presynaptic protein synthesis during the transition from short- to intermediate-term facilitation and may also initiate gene regulation to trigger the transition to long-term facilitation. These results suggest that a presynaptic ApNT feedback loop plays several key roles during consolidation of learning-related synaptic plasticity.}, } @article {pmid30397153, year = {2018}, author = {Smith, CN and Squire, LR}, title = {Awareness of what is learned as a characteristic of hippocampus-dependent memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11947-11952}, pmid = {30397153}, issn = {1091-6490}, mesh = {Aged ; Amnesia/physiopathology ; Awareness ; Eye Movement Measurements ; Eye Movements ; Female ; Hippocampus/*pathology ; Humans ; Learning/*physiology ; Male ; Memory/*physiology ; Memory Disorders ; Middle Aged ; Temporal Lobe/physiology ; }, abstract = {We explored the relationship between memory performance and conscious knowledge (or awareness) of what has been learned in memory-impaired patients with hippocampal lesions or larger medial temporal lesions. Participants viewed familiar scenes or familiar scenes where a change had been introduced. Patients identified many fewer of the changes than controls. Across all of the scenes, controls preferentially directed their gaze toward the regions that had been changed whenever they had what we term robust knowledge about the change: They could identify that a change occurred, report what had changed, and indicate where the change occurred. Preferential looking did not occur when they were unaware of the change or had only partial knowledge about it. The patients, overall, did not direct their gaze toward the regions that had been changed, but on the few occasions when they had robust knowledge about the change they (like controls) did exhibit this effect. Patients did not exhibit this effect when they were unaware of the change or had partial knowledge. The findings support the idea that awareness of what has been learned is a key feature of hippocampus-dependent memory.}, } @article {pmid30397152, year = {2018}, author = {Urban, MC}, title = {Escalator to extinction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11871-11873}, pmid = {30397152}, issn = {1091-6490}, mesh = {Animals ; Birds ; *Climate Change ; *Elevators and Escalators ; }, } @article {pmid30397151, year = {2018}, author = {Savinov, A and Block, SM}, title = {Self-cleavage of the glmS ribozyme core is controlled by a fragile folding element.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11976-11981}, pmid = {30397151}, issn = {1091-6490}, support = {R37 GM057035/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/metabolism ; Bacterial Proteins/metabolism ; Binding Sites/physiology ; Catalysis ; Catalytic Domain/physiology ; Ligands ; Nucleic Acid Conformation ; Optical Tweezers ; RNA, Catalytic/*chemistry/*metabolism ; Riboswitch/physiology ; Single Molecule Imaging/methods ; }, abstract = {Riboswitches modulate gene expression in response to small-molecule ligands. Switching is generally thought to occur via the stabilization of a specific RNA structure conferred by binding the cognate ligand. However, it is unclear whether any such stabilization occurs for riboswitches whose ligands also play functional roles, such as the glmS ribozyme riboswitch, which undergoes self-cleavage using its regulatory ligand, glucosamine 6-phosphate, as a catalytic cofactor. To address this question, it is necessary to determine both the conformational ensemble and its ligand dependence. We used optical tweezers to measure folding dynamics and cleavage rates for the core glmS ribozyme over a range of forces and ligand conditions. We found that the folding of a specific structural element, the P2.2 duplex, controls active-site formation and catalysis. However, the folded state is only weakly stable, regardless of cofactor concentration, supplying a clear exception to the ligand-based stabilization model of riboswitch function.}, } @article {pmid30397150, year = {2018}, author = {Fong, LY and Jing, R and Smalley, KJ and Wang, ZX and Taccioli, C and Fan, S and Chen, H and Alder, H and Huebner, K and Farber, JL and Fiehn, O and Croce, CM}, title = {Human-like hyperplastic prostate with low ZIP1 induced solely by Zn deficiency in rats.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11091-E11100}, pmid = {30397150}, issn = {1091-6490}, support = {R01 CA118560/CA/NCI NIH HHS/United States ; R35 CA197706/CA/NCI NIH HHS/United States ; U24 DK097154/DK/NIDDK NIH HHS/United States ; }, mesh = {Adenocarcinoma/genetics/*pathology ; Animals ; Cation Transport Proteins/*metabolism ; Cell Proliferation ; Citric Acid/metabolism ; Diet ; Disease Models, Animal ; Gene Expression Regulation, Neoplastic ; Humans ; Male ; MicroRNAs/biosynthesis ; Prostate/*pathology ; Prostatic Hyperplasia/genetics/*pathology ; Prostatic Neoplasms/genetics/*pathology ; Rats ; Rats, Sprague-Dawley ; Rats, Wistar ; Signal Transduction/genetics ; Transcription, Genetic/genetics ; Tumor Cells, Cultured ; Zinc/*deficiency/metabolism ; }, abstract = {Prostate cancer is a leading cause of cancer death in men over 50 years of age, and there is a characteristic marked decrease in Zn content in the malignant prostate cells. The cause and consequences of this loss have thus far been unknown. We found that in middle-aged rats a Zn-deficient diet reduces prostatic Zn levels (P = 0.025), increases cellular proliferation, and induces an inflammatory phenotype with COX-2 overexpression. This hyperplastic/inflammatory prostate has a human prostate cancer-like microRNA profile, with up-regulation of the Zn-homeostasis-regulating miR-183-96-182 cluster (fold change = 1.41-2.38; P = 0.029-0.0003) and down-regulation of the Zn importer ZIP1 (target of miR-182), leading to a reduction of prostatic Zn. This inverse relationship between miR-182 and ZIP1 also occurs in human prostate cancer tissue, which is known for Zn loss. The discovery that the Zn-depleted middle-aged rat prostate has a metabolic phenotype resembling that of human prostate cancer, with a 10-fold down-regulation of citric acid (P = 0.0003), links citrate reduction directly to prostatic Zn loss, providing the underlying mechanism linking dietary Zn deficiency with miR-183-96-182 overexpression, ZIP1 down-regulation, prostatic Zn loss, and the resultant citrate down-regulation, changes mimicking features of human prostate cancer. Thus, dietary Zn deficiency during rat middle age produces changes that mimic those of human prostate carcinoma and may increase the risk for prostate cancer, supporting the need for assessment of Zn supplementation in its prevention.}, } @article {pmid30397149, year = {2018}, author = {Davis, TH}, title = {QnAs with Emilio F. Moran.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11863-11864}, pmid = {30397149}, issn = {1091-6490}, } @article {pmid30397148, year = {2018}, author = {Sato, H and Takasaki, H and Takahashi, F and Suzuki, T and Iuchi, S and Mitsuda, N and Ohme-Takagi, M and Ikeda, M and Seo, M and Yamaguchi-Shinozaki, K and Shinozaki, K}, title = {Arabidopsis thaliana NGATHA1 transcription factor induces ABA biosynthesis by activating NCED3 gene during dehydration stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11178-E11187}, pmid = {30397148}, issn = {1091-6490}, mesh = {5' Untranslated Regions/genetics ; Abscisic Acid/*biosynthesis/genetics ; Arabidopsis/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Dioxygenases/genetics/*metabolism ; Droughts ; Gene Expression Regulation, Plant/*genetics ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified/genetics ; Promoter Regions, Genetic/genetics ; Stress, Physiological/*genetics/physiology ; Transcription Factors/genetics/*metabolism ; Transcriptional Activation/genetics ; }, abstract = {The plant hormone abscisic acid (ABA) is accumulated after drought stress and plays critical roles in the responses to drought stress in plants, such as gene regulation, stomatal closure, seed maturation, and dormancy. Although previous reports revealed detailed molecular roles of ABA in stress responses, the factors that contribute to the drought-stress responses-in particular, regulation of ABA accumulation-remain unclear. The enzyme NINE-CIS-EPOXYCAROTENOID DIOXYGENASE 3 (NCED3) is essential for ABA biosynthesis during drought stress, and the NCED3 gene is highly induced by drought stress. In the present study, we isolated NGATHAs (NGAs) as candidate transcriptional regulators of NCED3 through a screen of a plant library harboring the transcription factors fused to a chimeric repressor domain, SRDX. The NGA proteins were directly bound to a cis-element NGA-binding element (NBE) in the 5' untranslated region (5' UTR) of the NCED3 promoter and were suggested to be transcriptional activators of NCED3 Among the single-knockout mutants of four NGA family genes, we found that the NGATHA1 (NGA1) knockout mutant was drought-stress-sensitive with a decreased expression level of NCED3 during dehydration stress. These results suggested that NGA1 essentially functions as a transcriptional activator of NCED3 among the NGA family proteins. Moreover, the NGA1 protein was degraded under nonstressed conditions, and dehydration stress enhanced the accumulation of NGA1 proteins, even in ABA-deficient mutant plants, indicating that there should be ABA-independent posttranslational regulations. These findings emphasize the regulatory mechanisms of ABA biosynthesis during early drought stress.}, } @article {pmid30397147, year = {2018}, author = {Giddens, JP and Lomino, JV and DiLillo, DJ and Ravetch, JV and Wang, LX}, title = {Site-selective chemoenzymatic glycoengineering of Fab and Fc glycans of a therapeutic antibody.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12023-12027}, pmid = {30397147}, issn = {1091-6490}, support = {R01 GM080374/GM/NIGMS NIH HHS/United States ; R01 GM096973/GM/NIGMS NIH HHS/United States ; R35 CA196620/CA/NCI NIH HHS/United States ; }, mesh = {Antibodies, Monoclonal/chemistry ; Antibody-Dependent Cell Cytotoxicity/genetics/physiology ; Cetuximab/metabolism ; Glycoside Hydrolases/metabolism ; Glycosylation ; Humans ; Immunoglobulin Fab Fragments/*metabolism ; Immunoglobulin Fc Fragments/*metabolism ; Polysaccharides/metabolism ; Protein Engineering/*methods ; Substrate Specificity ; }, abstract = {The N-glycans attached to the Fab and Fc domains play distinct roles in modulating the functions of antibodies. However, posttranslational site-selective modifications of glycans in antibodies and other multiply glycosylated proteins remain a challenging task. Here, we report a chemoenzymatic method that permits independent manipulation of the Fab and Fc N-glycans, using cetuximab as a model therapeutic monoclonal antibody. Taking advantage of the substrate specificity of three endoglycosidases (Endo-S, Endo-S2, and Endo-F3) and their glycosynthase mutants, together with an unexpected substrate site-selectivity of a bacterial α1,6-fucosidase from Lactobacillus casei (AlfC), we were able to synthesize an optimal homogeneous glycoform of cetuximab in which the heterogeneous and immunogenic Fab N-glycans were replaced with a single sialylated N-glycan, and the core-fucosylated Fc N-glycans were remodeled with a nonfucosylated and fully galactosylated N-glycan. The glycoengineered cetuximab demonstrated increased affinity for the FcγIIIa receptor and significantly enhanced antibody-dependent cell-mediated cytotoxicity (ADCC) activity.}, } @article {pmid30397146, year = {2018}, author = {Glassman, SI and Weihe, C and Li, J and Albright, MBN and Looby, CI and Martiny, AC and Treseder, KK and Allison, SD and Martiny, JBH}, title = {Decomposition responses to climate depend on microbial community composition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11994-11999}, pmid = {30397146}, issn = {1091-6490}, mesh = {Altitude ; Bacteria/metabolism ; California ; Carbon Cycle/*physiology ; Climate Change ; Ecosystem ; Fungi/metabolism ; Microbiota/*physiology ; Plant Leaves/chemistry/microbiology ; }, abstract = {Bacteria and fungi drive decomposition, a fundamental process in the carbon cycle, yet the importance of microbial community composition for decomposition remains elusive. Here, we used an 18-month reciprocal transplant experiment along a climate gradient in Southern California to disentangle the effects of the microbial community versus the environment on decomposition. Specifically, we tested whether the decomposition response to climate change depends on the microbial community. We inoculated microbial decomposers from each site onto a common, irradiated leaf litter within "microbial cages" that prevent microbial exchange with the environment. We characterized fungal and bacterial composition and abundance over time and investigated the functional consequences through litter mass loss and chemistry. After 12 months, microbial communities altered both decomposition rate and litter chemistry. Further, the functional measurements depended on an interaction between the community and its climate in a manner not predicted by current theory. Moreover, microbial ecologists have traditionally considered fungi to be the primary agents of decomposition and for bacteria to play a minor role. Our results indicate that not only does climate change and transplantation have differential legacy effects among bacteria and fungi, but also that bacterial communities might be less functionally redundant than fungi with regards to decomposition. Thus, it may be time to reevaluate both the role of microbial community composition in its decomposition response to climate and the relative roles of bacterial and fungal communities in decomposition.}, } @article {pmid30397145, year = {2018}, author = {Moran, EF and Lopez, MC and Moore, N and Müller, N and Hyndman, DW}, title = {Sustainable hydropower in the 21st century.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11891-11898}, pmid = {30397145}, issn = {1091-6490}, abstract = {Hydropower has been the leading source of renewable energy across the world, accounting for up to 71% of this supply as of 2016. This capacity was built up in North America and Europe between 1920 and 1970 when thousands of dams were built. Big dams stopped being built in developed nations, because the best sites for dams were already developed and environmental and social concerns made the costs unacceptable. Nowadays, more dams are being removed in North America and Europe than are being built. The hydropower industry moved to building dams in the developing world and since the 1970s, began to build even larger hydropower dams along the Mekong River Basin, the Amazon River Basin, and the Congo River Basin. The same problems are being repeated: disrupting river ecology, deforestation, losing aquatic and terrestrial biodiversity, releasing substantial greenhouse gases, displacing thousands of people, and altering people's livelihoods plus affecting the food systems, water quality, and agriculture near them. This paper studies the proliferation of large dams in developing countries and the importance of incorporating climate change into considerations of whether to build a dam along with some of the governance and compensation challenges. We also examine the overestimation of benefits and underestimation of costs along with changes that are needed to address the legitimate social and environmental concerns of people living in areas where dams are planned. Finally, we propose innovative solutions that can move hydropower toward sustainable practices together with solar, wind, and other renewable sources.}, } @article {pmid30397144, year = {2018}, author = {Lapola, DM and Pinho, P and Quesada, CA and Strassburg, BBN and Rammig, A and Kruijt, B and Brown, F and Ometto, JPHB and Premebida, A and Marengo, JA and Vergara, W and Nobre, CA}, title = {Limiting the high impacts of Amazon forest dieback with no-regrets science and policy action.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11671-11679}, pmid = {30397144}, issn = {1091-6490}, mesh = {Brazil ; Climate Change ; Computer Simulation ; Conservation of Natural Resources/*economics ; Ecosystem ; Forestry/*economics/*methods ; Forests ; Policy ; Risk Assessment/methods ; Trees ; }, abstract = {Large uncertainties still dominate the hypothesis of an abrupt large-scale shift of the Amazon forest caused by climate change [Amazonian forest dieback (AFD)] even though observational evidence shows the forest and regional climate changing. Here, we assess whether mitigation or adaptation action should be taken now, later, or not at all in light of such uncertainties. No action/later action would result in major social impacts that may influence migration to large Amazonian cities through a causal chain of climate change and forest degradation leading to lower river-water levels that affect transportation, food security, and health. Net-present value socioeconomic damage over a 30-year period after AFD is estimated between US dollar (USD) $957 billion (×109) and $3,589 billion (compared with Gross Brazilian Amazon Product of USD $150 billion per year), arising primarily from changes in the provision of ecosystem services. Costs of acting now would be one to two orders of magnitude lower than economic damages. However, while AFD mitigation alternatives-e.g., curbing deforestation-are attainable (USD $64 billion), their efficacy in achieving a forest resilience that prevents AFD is uncertain. Concurrently, a proposed set of 20 adaptation measures is also attainable (USD $122 billion) and could bring benefits even if AFD never occurs. An interdisciplinary research agenda to fill lingering knowledge gaps and constrain the risk of AFD should focus on developing sound experimental and modeling evidence regarding its likelihood, integrated with socioeconomic assessments to anticipate its impacts and evaluate the feasibility and efficacy of mitigation/adaptation options.}, } @article {pmid30397143, year = {2018}, author = {Butler, EE and Mueller, ND and Huybers, P}, title = {Peculiarly pleasant weather for US maize.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11935-11940}, pmid = {30397143}, issn = {1091-6490}, mesh = {Agriculture/methods/*trends ; Climate Change ; Crops, Agricultural/growth & development ; Farmers ; Hot Temperature ; Seasons ; Temperature ; United States ; Weather ; Zea mays/*growth & development ; }, abstract = {Continuation of historical trends in crop yield are critical to meeting the demands of a growing and more affluent world population. Climate change may compromise our ability to meet these demands, but estimates vary widely, highlighting the importance of understanding historical interactions between yield and climate trends. The relationship between temperature and yield is nuanced, involving differential yield outcomes to warm ([Formula: see text]C) and hot ([Formula: see text]C) temperatures and differing sensitivity across growth phases. Here, we use a crop model that resolves temperature responses according to magnitude and growth phase to show that US maize has benefited from weather shifts since 1981. Improvements are related to lengthening of the growing season and cooling of the hottest temperatures. Furthermore, current farmer cropping schedules are more beneficial in the climate of the last decade than they would have been in earlier decades, indicating statistically significant adaptation to a changing climate of 13 kg·ha-1· decade-1 All together, the better weather experienced by US maize accounts for 28% of the yield trends since 1981. Sustaining positive trends in yield depends on whether improvements in agricultural climate continue and the degree to which farmers adapt to future climates.}, } @article {pmid30397142, year = {2018}, author = {York, RA and Patil, C and Abdilleh, K and Johnson, ZV and Conte, MA and Genner, MJ and McGrath, PT and Fraser, HB and Fernald, RD and Streelman, JT}, title = {Behavior-dependent cis regulation reveals genes and pathways associated with bower building in cichlid fishes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11081-E11090}, pmid = {30397142}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; Chromosome Mapping ; Cichlids/*genetics ; Gene Expression ; Gene Expression Regulation/genetics ; Genetic Variation/genetics ; Genome/genetics ; Genome-Wide Association Study ; Lakes ; Malawi ; Male ; }, abstract = {Many behaviors are associated with heritable genetic variation [Kendler and Greenspan (2006) Am J Psychiatry 163:1683-1694]. Genetic mapping has revealed genomic regions or, in a few cases, specific genes explaining part of this variation [Bendesky and Bargmann (2011) Nat Rev Gen 12:809-820]. However, the genetic basis of behavioral evolution remains unclear. Here we investigate the evolution of an innate extended phenotype, bower building, among cichlid fishes of Lake Malawi. Males build bowers of two types, pits or castles, to attract females for mating. We performed comparative genome-wide analyses of 20 bower-building species and found that these phenotypes have evolved multiple times with thousands of genetic variants strongly associated with this behavior, suggesting a polygenic architecture. Remarkably, F1 hybrids of a pit-digging and a castle-building species perform sequential construction of first a pit and then a castle bower. Analysis of brain gene expression in these hybrids showed that genes near behavior-associated variants display behavior-dependent allele-specific expression with preferential expression of the pit-digging species allele during pit digging and of the castle-building species allele during castle building. These genes are highly enriched for functions related to neurodevelopment and neural plasticity. Our results suggest that natural behaviors are associated with complex genetic architectures that alter behavior via cis-regulatory differences whose effects on gene expression are specific to the behavior itself.}, } @article {pmid30397141, year = {2018}, author = {Polato, NR and Gill, BA and Shah, AA and Gray, MM and Casner, KL and Barthelet, A and Messer, PW and Simmons, MP and Guayasamin, JM and Encalada, AC and Kondratieff, BC and Flecker, AS and Thomas, SA and Ghalambor, CK and Poff, NL and Funk, WC and Zamudio, KR}, title = {Narrow thermal tolerance and low dispersal drive higher speciation in tropical mountains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12471-12476}, doi = {10.1073/pnas.1809326115}, pmid = {30397141}, issn = {1091-6490}, abstract = {Species richness is greatest in the tropics, and much of this diversity is concentrated in mountains. Janzen proposed that reduced seasonal temperature variation selects for narrower thermal tolerances and limited dispersal along tropical elevation gradients [Janzen DH (1967) Am Nat 101:233-249]. These locally adapted traits should, in turn, promote reproductive isolation and higher speciation rates in tropical mountains compared with temperate ones. Here, we show that tropical and temperate montane stream insects have diverged in thermal tolerance and dispersal capacity, two key traits that are drivers of isolation in montane populations. Tropical species in each of three insect clades have markedly narrower thermal tolerances and lower dispersal than temperate species, resulting in significantly greater population divergence, higher cryptic diversity, higher tropical speciation rates, and greater accumulation of species over time. Our study also indicates that tropical montane species, with narrower thermal tolerance and reduced dispersal ability, will be especially vulnerable to rapid climate change.}, } @article {pmid30397140, year = {2018}, author = {Martin, PR and Bonier, F}, title = {Species interactions limit the occurrence of urban-adapted birds in cities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {E11495-E11504}, doi = {10.1073/pnas.1809317115}, pmid = {30397140}, issn = {1091-6490}, abstract = {Urbanization represents an extreme transformation of more natural systems. Populations of most species decline or disappear with urbanization, and yet some species persist and even thrive in cities. What determines which species persist or thrive in urban habitats? Direct competitive interactions among species can influence their distributions and resource use, particularly along gradients of environmental challenge. Given the challenges of urbanization, similar interactions may be important for determining which species persist or thrive in cities; however, their role remains poorly understood. Here, we use a global dataset to test among three alternative hypotheses for how direct competitive interactions and behavioral dominance may influence the breeding occurrence of birds in cities. We find evidence to support the competitive interference hypothesis: behaviorally dominant species were more widespread in urban habitats than closely related subordinate species, but only in taxa that thrive in urban environments (hereafter, urban adapted), and only when dominant and subordinate species overlapped their geographic ranges. This result was evident across diverse phylogenetic groups but varied significantly with a country's level of economic development. Urban-adapted, dominant species were more widespread than closely related subordinate species in cities in developed, but not developing, countries; countries in economic transition showed an intermediate pattern. Our results provide evidence that competitive interactions broadly influence species responses to urbanization, and that these interactions have asymmetric effects on subordinate species that otherwise could be widespread in urban environments. Results further suggest that economic development might accentuate the consequences of competitive interactions, thereby reducing local diversity in cities.}, } @article {pmid30397139, year = {2018}, author = {Hruschka, DJ and Medin, DL and Rogoff, B and Henrich, J}, title = {Pressing questions in the study of psychological and behavioral diversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11366-11368}, pmid = {30397139}, issn = {1091-6490}, } @article {pmid30397138, year = {2018}, author = {Hruschka, DJ and Munira, S and Jesmin, K and Hackman, J and Tiokhin, L}, title = {Learning from failures of protocol in cross-cultural research.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11428-11434}, pmid = {30397138}, issn = {1091-6490}, abstract = {The many tools that social and behavioral scientists use to gather data from their fellow humans have, in most cases, been honed on a rarefied subset of humanity: highly educated participants with unique capacities, experiences, motivations, and social expectations. Through this honing process, researchers have developed protocols that extract information from these participants with great efficiency. However, as researchers reach out to broader populations, it is unclear whether these highly refined protocols are robust to cultural differences in skills, motivations, and expected modes of social interaction. In this paper, we illustrate the kinds of mismatches that can arise when using these highly refined protocols with nontypical populations by describing our experience translating an apparently simple social discounting protocol to work in rural Bangladesh. Multiple rounds of piloting and revision revealed a number of tacit assumptions about how participants should perceive, understand, and respond to key elements of the protocol. These included facility with numbers, letters, abstract number lines, and 2D geometric shapes, and the treatment of decisions as a series of isolated events. Through on-the-ground observation and a collaborative refinement process, we developed a protocol that worked both in Bangladesh and among US college students. More systematic study of the process of adapting common protocols to new contexts will provide valuable information about the range of skills, motivations, and modes of interaction that participants bring to studies as we develop a more diverse and inclusive social and behavioral science.}, } @article {pmid30397137, year = {2018}, author = {Alcalá, L and Rogoff, B and López Fraire, A}, title = {Sophisticated collaboration is common among Mexican-heritage US children.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11377-11384}, pmid = {30397137}, issn = {1091-6490}, abstract = {In light of calls for improving people's skill in collaboration, this paper examines strengths in processes of collaboration of Mexican immigrant children. Sibling pairs (6-10 years old) in California were asked to collaborate in planning the shortest route through a model grocery store. On average, 14 sibling pairs with Mexican Indigenous-heritage backgrounds engaged together collaboratively as an ensemble, making decisions in common and fluidly building on each other's ideas, more often than 16 middle-class European American sibling pairs, who on average more often divided decision making into a solo activity (often ignoring the other or simply bossing the other). Siblings who spent more time collaborating fluidly as an ensemble in the shared planning task were also more likely to collaborate with initiative at home, according to their mothers, which suggests that family socialization practices may contribute to cultural differences in collaboration.}, } @article {pmid30397136, year = {2018}, author = {Miller, GE and Chen, E and Armstrong, CC and Carroll, AL and Ozturk, S and Rydland, KJ and Brody, GH and Parrish, TB and Nusslock, R}, title = {Functional connectivity in central executive network protects youth against cardiometabolic risks linked with neighborhood violence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12063-12068}, pmid = {30397136}, issn = {1091-6490}, support = {T32 NS047987/NS/NINDS NIH HHS/United States ; }, mesh = {Adaptation, Psychological/*physiology ; Adolescent ; Brain/diagnostic imaging/physiopathology ; Brain Mapping/methods ; Cerebral Cortex/physiopathology ; Child ; Connectome ; Executive Function/*physiology ; Female ; Heart Diseases/metabolism/*prevention & control ; Humans ; Male ; Metabolic Syndrome/metabolism/*prevention & control ; Nerve Net/diagnostic imaging/*physiopathology ; Obesity/metabolism/prevention & control ; Resilience, Psychological ; Risk ; Risk Factors ; Socioeconomic Factors ; *Violence ; }, abstract = {Although violent crime has declined in recent decades, it remains a recurring feature of daily life in some neighborhoods. Mounting evidence indicates that such violence has a long reach, which goes beyond family and friends of the victim and undermines the health of people in the surrounding community. However, like all forms of adversity, community violence elicits a heterogeneous response: Some remain healthy, but others deteriorate. Despite much scientific attention, the neural circuitries that contribute to differential adaptation remain poorly understood. Drawing on knowledge of the brain's intrinsic functional architecture, we predicted that individual differences in resting-state connectivity would explain variability in the strength of the association between neighborhood violence and cardiometabolic health. We enrolled 218 urban youth (age 12-14 years, 66% female; 65% black or Latino) and used geocoding to characterize their exposure to neighborhood murder over the past five years. Multiple aspects of cardiometabolic health were assessed, including obesity, insulin resistance, and metabolic syndrome. Functional MRI was used to quantify the connectivity of major intrinsic networks. Consistent with predictions, resting-state connectivity within the central executive network (CEN) emerged as a moderator of adaptation. Across six distinct outcomes, a higher neighborhood murder rate was associated with greater cardiometabolic risk, but this relationship was apparent only among youth who displayed lower CEN resting-state connectivity. By contrast, there was little evidence of moderation by the anterior salience and default mode networks. These findings advance basic and applied knowledge about adaptation by highlighting intrinsic CEN connectivity as a potential neurobiological contributor to resilience.}, } @article {pmid30397135, year = {2018}, author = {Majid, A and Roberts, SG and Cilissen, L and Emmorey, K and Nicodemus, B and O'Grady, L and Woll, B and LeLan, B and de Sousa, H and Cansler, BL and Shayan, S and de Vos, C and Senft, G and Enfield, NJ and Razak, RA and Fedden, S and Tufvesson, S and Dingemanse, M and Ozturk, O and Brown, P and Hill, C and Le Guen, O and Hirtzel, V and van Gijn, R and Sicoli, MA and Levinson, SC}, title = {Differential coding of perception in the world's languages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11369-11376}, pmid = {30397135}, issn = {1091-6490}, support = {R01 DC010997/DC/NIDCD NIH HHS/United States ; }, abstract = {Is there a universal hierarchy of the senses, such that some senses (e.g., vision) are more accessible to consciousness and linguistic description than others (e.g., smell)? The long-standing presumption in Western thought has been that vision and audition are more objective than the other senses, serving as the basis of knowledge and understanding, whereas touch, taste, and smell are crude and of little value. This predicts that humans ought to be better at communicating about sight and hearing than the other senses, and decades of work based on English and related languages certainly suggests this is true. However, how well does this reflect the diversity of languages and communities worldwide? To test whether there is a universal hierarchy of the senses, stimuli from the five basic senses were used to elicit descriptions in 20 diverse languages, including 3 unrelated sign languages. We found that languages differ fundamentally in which sensory domains they linguistically code systematically, and how they do so. The tendency for better coding in some domains can be explained in part by cultural preoccupations. Although languages seem free to elaborate specific sensory domains, some general tendencies emerge: for example, with some exceptions, smell is poorly coded. The surprise is that, despite the gradual phylogenetic accumulation of the senses, and the imbalances in the neural tissue dedicated to them, no single hierarchy of the senses imposes itself upon language.}, } @article {pmid30397134, year = {2018}, author = {Brady, LM and Fryberg, SA and Shoda, Y}, title = {Expanding the interpretive power of psychological science by attending to culture.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11406-11413}, pmid = {30397134}, issn = {1091-6490}, abstract = {A lack of interpretive power (i.e., the ability to understand individuals' experiences and behaviors in relation to their cultural contexts) undermines psychology's understanding of diverse psychological phenomena. Building interpretive power requires attending to cultural influences in research. We describe three characteristics of research that lacks interpretive power: normalizing and overgeneralizing from behaviors and processes of people in Western, educated, industrialized, rich, and democratic (WEIRD) contexts; making non-WEIRD people and processes invisible; and misapplying WEIRD findings in non-WEIRD contexts. We also describe research in which leveraging interpretive power prevented these negative consequences. Finally, using the culture-cycle framework, we outline a vision for creating culture change within psychology by implementing culture-conscious practices to guide the formation of research questions, empirical design, and data analysis and interpretation.}, } @article {pmid30397133, year = {2018}, author = {Puckerin, AA and Chang, DD and Shuja, Z and Choudhury, P and Scholz, J and Colecraft, HM}, title = {Engineering selectivity into RGK GTPase inhibition of voltage-dependent calcium channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12051-12056}, pmid = {30397133}, issn = {1091-6490}, support = {R01 HL084332/HL/NHLBI NIH HHS/United States ; T32 HL120826/HL/NHLBI NIH HHS/United States ; }, mesh = {Biophysical Phenomena ; Calcium/metabolism ; Calcium Channel Blockers/*metabolism ; Calcium Channels/*genetics/metabolism ; Calcium Channels, L-Type/metabolism ; Calcium Channels, N-Type/metabolism ; HEK293 Cells ; Humans ; Ion Channel Gating/physiology ; Monomeric GTP-Binding Proteins/*metabolism ; Myocytes, Cardiac/metabolism ; Neurons/metabolism ; Protein Engineering/methods ; Substrate Specificity/genetics ; ras Proteins/metabolism ; }, abstract = {Genetically encoded inhibitors for voltage-dependent Ca2+ (CaV) channels (GECCIs) are useful research tools and potential therapeutics. Rad/Rem/Rem2/Gem (RGK) proteins are Ras-like G proteins that potently inhibit high voltage-activated (HVA) Ca2+ (CaV1/CaV2 family) channels, but their nonselectivity limits their potential applications. We hypothesized that nonselectivity of RGK inhibition derives from their binding to auxiliary CaVβ-subunits. To investigate latent CaVβ-independent components of inhibition, we coexpressed each RGK individually with CaV1 (CaV1.2/CaV1.3) or CaV2 (CaV2.1/CaV2.2) channels reconstituted in HEK293 cells with either wild-type (WT) β2a or a mutant version (β2a,TM) that does not bind RGKs. All four RGKs strongly inhibited CaV1/CaV2 channels reconstituted with WT β2a By contrast, when channels were reconstituted with β2a,TM, Rem inhibited only CaV1.2, Rad selectively inhibited CaV1.2 and CaV2.2, while Gem and Rem2 were ineffective. We generated mutant RGKs (Rem[R200A/L227A] and Rad[R208A/L235A]) unable to bind WT CaVβ, as confirmed by fluorescence resonance energy transfer. Rem[R200A/L227A] selectively blocked reconstituted CaV1.2 while Rad[R208A/L235A] inhibited CaV1.2/CaV2.2 but not CaV1.3/CaV2.1. Rem[R200A/L227A] and Rad[R208A/L235A] both suppressed endogenous CaV1.2 channels in ventricular cardiomyocytes and selectively blocked 25 and 62%, respectively, of HVA currents in somatosensory neurons of the dorsal root ganglion, corresponding to their distinctive selectivity for CaV1.2 and CaV1.2/CaV2.2 channels. Thus, we have exploited latent β-binding-independent Rem and Rad inhibition of specific CaV1/CaV2 channels to develop selective GECCIs with properties unmatched by current small-molecule CaV channel blockers.}, } @article {pmid30397132, year = {2018}, author = {Janczura, KJ and Volmar, CH and Sartor, GC and Rao, SJ and Ricciardi, NR and Lambert, G and Brothers, SP and Wahlestedt, C}, title = {Inhibition of HDAC3 reverses Alzheimer's disease-related pathologies in vitro and in the 3xTg-AD mouse model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11148-E11157}, pmid = {30397132}, issn = {1091-6490}, support = {K99 DA040744/DA/NIDA NIH HHS/United States ; }, mesh = {Acetylation/drug effects ; Acrylamides/*pharmacology ; Alzheimer Disease/drug therapy/*pathology ; Amyloid beta-Peptides/*metabolism ; Animals ; Brain-Derived Neurotrophic Factor/metabolism ; Gene Silencing ; HEK293 Cells ; Histone Deacetylase Inhibitors/*pharmacology ; Histone Deacetylases/genetics/*metabolism ; Histones/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology ; Memory/*drug effects ; Mice ; Mice, Transgenic ; Neprilysin/blood ; Neurons/cytology ; Phenylenediamines/*pharmacology ; Phosphorylation/drug effects ; Spatial Learning/*drug effects ; tau Proteins/*metabolism ; }, abstract = {Alzheimer's disease (AD) is the leading cause of age-related dementia. Neuropathological hallmarks of AD include brain deposition of β-amyloid (Aβ) plaques and accumulation of both hyperphosphorylated and acetylated tau. RGFP-966, a brain-penetrant and selective HDAC3 inhibitor, or HDAC3 silencing, increases BDNF expression, increases histone H3 and H4 acetylation, decreases tau phosphorylation and tau acetylation at disease-associated sites, reduces β-secretase cleavage of the amyloid precursor protein (APP), and decreases Aβ1-42 accumulation in HEK-293 cells overexpressing APP with the double Swedish mutation (HEK/APPsw). In the triple transgenic AD mouse model (3xTg-AD), repeated administration of 3 and 10 mg/kg of RGFP-966 reverses pathological tau phosphorylation at Thr181, Ser202, and Ser396, increases levels of the Aβ degrading enzyme Neprilysin in plasma, decreases Aβ1-42 protein levels in the brain and periphery, and improves spatial learning and memory. Finally, we show that RGFP-966 decreases Aβ1-42 accumulation and both tau acetylation and phosphorylation at disease residues in neurons derived from induced pluripotent stem cells obtained from APOEε4-carrying AD patients. These data indicate that HDAC3 plays an important regulatory role in the expression and regulation of proteins associated with AD pathophysiology, supporting the notion that HDAC3 may be a disease-modifying therapeutic target.}, } @article {pmid30397131, year = {2018}, author = {Green, JP and Hatchwell, BJ}, title = {Inclusive fitness consequences of dispersal decisions in a cooperatively breeding bird, the long-tailed tit (Aegithalos caudatus).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12011-12016}, pmid = {30397131}, issn = {1091-6490}, mesh = {Animal Migration/*physiology ; Animals ; Behavior, Animal/physiology ; Biological Evolution ; Breeding ; Cooperative Behavior ; Female ; Gene Flow/physiology ; Male ; Mating Preference, Animal/*physiology ; Passeriformes/physiology ; Population Dynamics ; Reproduction ; Sexual Behavior, Animal/*physiology ; Songbirds/physiology ; }, abstract = {Natal dispersal is a demographic trait with profound evolutionary, ecological, and behavioral consequences. However, our understanding of the adaptive value of dispersal patterns is severely hampered by the difficulty of measuring the relative fitness consequences of alternative dispersal strategies in natural populations. This is especially true in social species, in which natal philopatry allows kin selection to operate, so direct and indirect components of inclusive fitness have to be considered when evaluating selection on dispersal. Here, we use lifetime reproductive success data from a long-term study of a cooperative breeder, the long-tailed tit Aegithalos caudatus, to quantify the direct and indirect components of inclusive fitness. We show that dispersal has a negative effect on the accrual of indirect fitness, and hence inclusive fitness, by males. In contrast, the inclusive, predominantly direct, fitness of females increases with dispersal distance. We conclude that the conflicting fitness consequences of dispersal in this species result in sexually antagonistic selection on this key demographic parameter.}, } @article {pmid30397130, year = {2018}, author = {Niwa, S and Takeda, K and Kosugi, M and Tsutsumi, E and Mogi, T and Miki, K}, title = {Crystal structure of heme A synthase from Bacillus subtilis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11953-11957}, pmid = {30397130}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Bacillus subtilis/metabolism ; Bacterial Proteins/*chemistry/metabolism/*ultrastructure ; Binding Sites ; Crystallography, X-Ray/methods ; Cytochrome b Group/*chemistry/*ultrastructure ; Heme/analogs & derivatives/metabolism ; Membrane Proteins/*chemistry/metabolism/*ultrastructure ; Models, Molecular ; Oxidoreductases/metabolism ; }, abstract = {Heme A is an essential cofactor for respiratory terminal oxidases and vital for respiration in aerobic organisms. The final step of heme A biosynthesis is formylation of the C-8 methyl group of heme molecule by heme A synthase (HAS). HAS is a heme-containing integral membrane protein, and its structure and reaction mechanisms have remained unknown. Thus, little is known about HAS despite of its importance. Here we report the crystal structure of HAS from Bacillus subtilis at 2.2-Å resolution. The N- and C-terminal halves of HAS consist of four-helix bundles and they align in a pseudo twofold symmetry manner. Each bundle contains a pair of histidine residues and forms a heme-binding domain. The C-half domain binds a cofactor-heme molecule, while the N-half domain is vacant. Many water molecules are found in the transmembrane region and around the substrate-binding site, and some of them interact with the main chain of transmembrane helix. Comparison of these two domain structures enables us to construct a substrate-heme binding state structure. This structure implies that a completely conserved glutamate, Glu57 in B. subtilis, is the catalytic residue for the formylation reaction. These results provide valuable suggestions of the substrate-heme binding mechanism. Our results present significant insight into the heme A biosynthesis.}, } @article {pmid30397129, year = {2018}, author = {Kubitza, C and Bittner, F and Ginsel, C and Havemeyer, A and Clement, B and Scheidig, AJ}, title = {Crystal structure of human mARC1 reveals its exceptional position among eukaryotic molybdenum enzymes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11958-11963}, pmid = {30397129}, issn = {1091-6490}, mesh = {Catalysis ; Coenzymes ; Crystallography, X-Ray/methods ; Eukaryotic Cells/metabolism ; Humans ; Metalloproteins ; Mitochondria/metabolism ; Mitochondrial Proteins/*chemistry/metabolism/*ultrastructure ; Molybdenum/metabolism ; Oxidation-Reduction ; Oxidoreductases/*chemistry/metabolism/*ultrastructure ; Protein Structure, Tertiary ; Pteridines ; }, abstract = {Biotransformation enzymes ensure a viable homeostasis by regulating reversible cycles of oxidative and reductive reactions. The metabolism of nitrogen-containing compounds is of high pharmaceutical and toxicological relevance because N-oxygenated metabolites derived from reactions mediated by cytochrome P450 enzymes or flavin-dependent monooxygenases are in some cases highly toxic or mutagenic. The molybdenum-dependent mitochondrial amidoxime-reducing component (mARC) was found to be an extremely efficient counterpart, which is able to reduce the full range of N-oxygenated compounds and thereby mediates detoxification reactions. However, the 3D structure of this enzyme was unknown. Here we present the high-resolution crystal structure of human mARC. We give detailed insight into the coordination of its molybdenum cofactor (Moco), the catalytic mechanism, and its ability to reduce a wide range of N-oxygenated compounds. The identification of two key residues will allow future discrimination between mARC paralogs and ensure correct annotation. Since our structural findings contradict in silico predictions that are currently made by online databases, we propose domain definitions for members of the superfamily of Moco sulfurase C-terminal (MOSC) domain-containing proteins. Furthermore, we present evidence for an evolutionary role of mARC for the emergence of the xanthine oxidase protein superfamily. We anticipate the hereby presented crystal structure to be a starting point for future descriptions of MOSC proteins, which are currently poorly structurally characterized.}, } @article {pmid30397128, year = {2018}, author = {Paudel, BP and Fiorini, E and Börner, R and Sigel, RKO and Rueda, DS}, title = {Optimal molecular crowding accelerates group II intron folding and maximizes catalysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11917-11922}, pmid = {30397128}, issn = {1091-6490}, support = {259092//European Research Council/International ; MC-A658-5TY10//Medical Research Council/United Kingdom ; }, mesh = {Catalysis/drug effects ; Cell Biology ; Computational Biology/methods ; Fluorescence Resonance Energy Transfer/methods ; Intracellular Space/*physiology ; Magnesium/metabolism ; Molecular Dynamics Simulation ; Nucleic Acid Conformation ; Polyethylene Glycols ; Protein Folding/drug effects ; RNA, Catalytic/metabolism/physiology ; RNA, Ribosomal, Self-Splicing/metabolism/*physiology ; }, abstract = {Unlike in vivo conditions, group II intron ribozymes are known to require high magnesium(II) concentrations ([Mg2+]) and high temperatures (42 °C) for folding and catalysis in vitro. A possible explanation for this difference is the highly crowded cellular environment, which can be mimicked in vitro by macromolecular crowding agents. Here, we combined bulk activity assays and single-molecule Förster Resonance Energy Transfer (smFRET) to study the influence of polyethylene glycol (PEG) on catalysis and folding of the ribozyme. Our activity studies reveal that PEG reduces the [Mg2+] required, and we found an "optimum" [PEG] that yields maximum activity. smFRET experiments show that the most compact state population, the putative active state, increases with increasing [PEG]. Dynamic transitions between folded states also increase. Therefore, this study shows that optimal molecular crowding concentrations help the ribozyme not only to reach the native fold but also to increase its in vitro activity to approach that in physiological conditions.}, } @article {pmid30397127, year = {2018}, author = {Lai, M and Obliger, A and Lu, D and Kley, CS and Bischak, CG and Kong, Q and Lei, T and Dou, L and Ginsberg, NS and Limmer, DT and Yang, P}, title = {Intrinsic anion diffusivity in lead halide perovskites is facilitated by a soft lattice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11929-11934}, pmid = {30397127}, issn = {1091-6490}, abstract = {Facile ionic transport in lead halide perovskites plays a critical role in device performance. Understanding the microscopic origins of high ionic conductivities has been complicated by indirect measurements and sample microstructural heterogeneities. Here, we report the direct visualization of halide anion interdiffusion in CsPbCl3-CsPbBr3 single crystalline perovskite nanowire heterojunctions using wide-field and confocal photoluminescence measurements. The combination of nanoscale imaging techniques with these single crystalline materials allows us to measure intrinsic anionic lattice diffusivities, free from complications of microscale inhomogeneity. Halide diffusivities were found to be between 10-13 and ∼10-12 cm2/second at about 100 °C, which are several orders of magnitudes lower than those reported in polycrystalline thin films. Spatially resolved photoluminescence lifetimes and surface potential measurements provide evidence of the central role of halide vacancies in facilitating ionic diffusion. Vacancy formation free energies computed from molecular simulation are small due to the easily deformable perovskite lattice, accounting for the high equilibrium vacancy concentration. Furthermore, molecular simulations suggest that ionic motion is facilitated by low-frequency lattice modes, resulting in low activation barriers for vacancy-mediated transport. This work elucidates the intrinsic solid-state ion diffusion mechanisms in this class of semisoft materials and offers guidelines for engineering materials with long-term stability in functional devices.}, } @article {pmid30397126, year = {2018}, author = {Jeffery, JE and Storrs, GW and Holland, T and Tabin, CJ and Ahlberg, PE}, title = {Unique pelvic fin in a tetrapod-like fossil fish, and the evolution of limb patterning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12005-12010}, pmid = {30397126}, issn = {1091-6490}, mesh = {Animal Fins/*anatomy & histology/embryology ; Animals ; Biological Evolution ; Body Patterning/*physiology ; Extremities/anatomy & histology/*embryology ; Femur/anatomy & histology ; Fishes/anatomy & histology/classification ; Fossils/anatomy & histology ; Phylogeny ; Skeleton ; }, abstract = {All living tetrapods have a one-to-two branching pattern in the embryonic proximal limb skeleton, with a single element at the base of the limb (the humerus or femur) that articulates distally with two parallel radials (the ulna and radius or the tibia and fibula). This pattern is also seen in the fossilized remains of stem-tetrapods, including the fishlike members of the group, in which despite the absence of digits, the proximal parts of the fin skeleton clearly resemble those of later tetrapods. However, little is known about the developmental mechanisms that establish and canalize this highly conserved pattern. We describe the well-preserved pelvic fin skeleton of Rhizodus hibberti, a Carboniferous sarcopterygian (lobe-finned) fish, and member of the tetrapod stem group. In this specimen, three parallel radials, each robust with a distinct morphology, articulate with the femur. We review this unexpected morphology in a phylogenetic and developmental context. It implies that the developmental patterning mechanisms seen in living tetrapods, now highly constrained, evolved from mechanisms flexible enough to accommodate variation in the zeugopod (even between pectoral and pelvic fins), while also allowing each element to have a unique morphology.}, } @article {pmid30397125, year = {2018}, author = {Jeong, C and Wilkin, S and Amgalantugs, T and Bouwman, AS and Taylor, WTT and Hagan, RW and Bromage, S and Tsolmon, S and Trachsel, C and Grossmann, J and Littleton, J and Makarewicz, CA and Krigbaum, J and Burri, M and Scott, A and Davaasambuu, G and Wright, J and Irmer, F and Myagmar, E and Boivin, N and Robbeets, M and Rühli, FJ and Krause, J and Frohlich, B and Hendy, J and Warinner, C}, title = {Bronze Age population dynamics and the rise of dairy pastoralism on the eastern Eurasian steppe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11248-E11255}, pmid = {30397125}, issn = {1091-6490}, support = {T32 ES007069/ES/NIEHS NIH HHS/United States ; }, abstract = {Recent paleogenomic studies have shown that migrations of Western steppe herders (WSH) beginning in the Eneolithic (ca. 3300-2700 BCE) profoundly transformed the genes and cultures of Europe and central Asia. Compared with Europe, however, the eastern extent of this WSH expansion is not well defined. Here we present genomic and proteomic data from 22 directly dated Late Bronze Age burials putatively associated with early pastoralism in northern Mongolia (ca. 1380-975 BCE). Genome-wide analysis reveals that they are largely descended from a population represented by Early Bronze Age hunter-gatherers in the Baikal region, with only a limited contribution (∼7%) of WSH ancestry. At the same time, however, mass spectrometry analysis of dental calculus provides direct protein evidence of bovine, sheep, and goat milk consumption in seven of nine individuals. No individuals showed molecular evidence of lactase persistence, and only one individual exhibited evidence of >10% WSH ancestry, despite the presence of WSH populations in the nearby Altai-Sayan region for more than a millennium. Unlike the spread of Neolithic farming in Europe and the expansion of Bronze Age pastoralism on the Western steppe, our results indicate that ruminant dairy pastoralism was adopted on the Eastern steppe by local hunter-gatherers through a process of cultural transmission and minimal genetic exchange with outside groups.}, } @article {pmid30397124, year = {2018}, author = {Roy, SG and Uchida, E and de Souza, SP and Blachly, B and Fox, E and Gardner, K and Gold, AJ and Jansujwicz, J and Klein, S and McGreavy, B and Mo, W and Smith, SMC and Vogler, E and Wilson, K and Zydlewski, J and Hart, D}, title = {A multiscale approach to balance trade-offs among dam infrastructure, river restoration, and cost.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12069-12074}, pmid = {30397124}, issn = {1091-6490}, mesh = {Conservation of Natural Resources/*methods ; Cost-Benefit Analysis/*methods ; Ecology ; Ecosystem ; Environmental Restoration and Remediation/*economics/methods ; New England ; Rivers/chemistry ; United States ; Water Supply/economics ; }, abstract = {Aging infrastructure and growing interests in river restoration have led to a substantial rise in dam removals in the United States. However, the decision to remove a dam involves many complex trade-offs. The benefits of dam removal for hazard reduction and ecological restoration are potentially offset by the loss of hydroelectricity production, water supply, and other important services. We use a multiobjective approach to examine a wide array of trade-offs and synergies involved with strategic dam removal at three spatial scales in New England. We find that increasing the scale of decision-making improves the efficiency of trade-offs among ecosystem services, river safety, and economic costs resulting from dam removal, but this may lead to heterogeneous and less equitable local-scale outcomes. Our model may help facilitate multilateral funding, policy, and stakeholder agreements by analyzing the trade-offs of coordinated dam decisions, including net benefit alternatives to dam removal, at scales that satisfy these agreements.}, } @article {pmid30397123, year = {2018}, author = {Meng, W and Clerico, EM and McArthur, N and Gierasch, LM}, title = {Allosteric landscapes of eukaryotic cytoplasmic Hsp70s are shaped by evolutionary tuning of key interfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11970-11975}, pmid = {30397123}, issn = {1091-6490}, mesh = {Allosteric Regulation/genetics ; Allosteric Site/genetics ; Animals ; Computational Biology/methods ; Cytoplasm/metabolism ; Cytosol/metabolism ; Escherichia coli/metabolism ; Escherichia coli Proteins/metabolism ; Eukaryota/genetics/metabolism ; Eukaryotic Cells/metabolism ; Evolution, Molecular ; HSC70 Heat-Shock Proteins/*metabolism ; HSP70 Heat-Shock Proteins/*metabolism ; Heat-Shock Proteins/genetics/metabolism ; Humans ; Models, Molecular ; Protein Conformation ; Protein Domains ; }, abstract = {The 70-kDa heat shock proteins (Hsp70s) are molecular chaperones that perform a wide range of critical cellular functions. They assist in the folding of newly synthesized proteins, facilitate assembly of specific protein complexes, shepherd proteins across membranes, and prevent protein misfolding and aggregation. Hsp70s perform these functions by a conserved mechanism that relies on allosteric cycles of nucleotide-modulated binding and release of client proteins. Current models for Hsp70 allostery have come from extensive study of the bacterial Hsp70, DnaK. Extending our understanding to eukaryotic Hsp70s is extremely important not only in providing a likely common mechanistic framework but also because of their central roles in cellular physiology. In this study, we examined the allosteric behaviors of the eukaryotic cytoplasmic Hsp70s, HspA1 and Hsc70, and found significant differences from that of DnaK. We found that HspA1 and Hsc70 favor a state in which the nucleotide-binding domain (NBD) and substrate-binding domain (SBD) are intimately docked significantly more as compared to DnaK. Past work established that the NBD-SBD interface and the helical lid-β-SBD interface govern the allosteric landscape of DnaK. Here, we identified sites on these interfaces that differ between eukaryotic cytoplasmic Hsp70s and DnaK. Our mutational analysis has revealed key evolutionary variations that account for the population shifts between the docked and undocked conformations. These results underline the tunability of Hsp70 functions by modulation of allosteric interfaces through evolutionary diversification and also suggest sites where the binding of small-molecule modulators could influence Hsp70 function.}, } @article {pmid30397122, year = {2018}, author = {Barat, E and Wirth, S and Duhamel, JR}, title = {Face cells in orbitofrontal cortex represent social categories.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11158-E11167}, pmid = {30397122}, issn = {1091-6490}, mesh = {Animals ; Emotions/*physiology ; Face/*physiology ; *Facial Expression ; Female ; *Interpersonal Relations ; Macaca mulatta ; Male ; Neurons/physiology ; Perception ; Prefrontal Cortex/*physiology ; Temporal Lobe/physiology ; Vocalization, Animal ; }, abstract = {Perceiving social and emotional information from faces is a critical primate skill. For this purpose, primates evolved dedicated cortical architecture, especially in occipitotemporal areas, utilizing face-selective cells. Less understood face-selective neurons are present in the orbitofrontal cortex (OFC) and are our object of study. We examined 179 face-selective cells in the lateral sulcus of the OFC by characterizing their responses to a rich set of photographs of conspecific faces varying in age, gender, and facial expression. Principal component analysis and unsupervised cluster analysis of stimulus space both revealed that face cells encode face dimensions for social categories and emotions. Categories represented strongly were facial expressions (grin and threat versus lip smack), juvenile, and female monkeys. Cluster analyses of a control population of nearby cells lacking face selectivity did not categorize face stimuli in a meaningful way, suggesting that only face-selective cells directly support face categorization in OFC. Time course analyses of face cell activity from stimulus onset showed that faces were discriminated from nonfaces early, followed by within-face categorization for social and emotion content (i.e., young and facial expression). Face cells revealed no response to acoustic stimuli such as vocalizations and were poorly modulated by vocalizations added to faces. Neuronal responses remained stable when paired with positive or negative reinforcement, implying that face cells encode social information but not learned reward value associated to faces. Overall, our results shed light on a substantial role of the OFC in the characterizations of facial information bearing on social and emotional behavior.}, } @article {pmid30397121, year = {2018}, author = {Keller, H}, title = {Universality claim of attachment theory: Children's socioemotional development across cultures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11414-11419}, pmid = {30397121}, issn = {1091-6490}, abstract = {The first part of this paper reviews the basic tenets of attachment theory with respect to differences in cultural socialization strategies. In one strategy infants have the lead, and the social environment is responsive to the infant's wishes and preferences. In another strategy the caregivers-children or adults-are experts who know what is best for a baby without exploring his or her mental states. Accordingly, the definition of attachment is conceived as a negotiable emotional bond or a network of responsibilities. Attachment theory represents the Western middle-class perspective, ignoring the caregiving values and practices in the majority of the world. However, attachment theory claims universality in all its components. Since the claim of universality implies moral judgments about good and bad parenting, ethical questions need to be addressed. These issues are discussed in the second part of the paper. It is first demonstrated that sensitive responsiveness in attachment theory is built on a different concept of the person and self than concepts of good caregiving in many rural subsistence-based farming families. Evaluating one system with the standards of another ignores different realities and different value systems. The common practice of large-scale interventions in rural subsistence-based contexts promoting Western-style parenting strategies without knowing the local culture positions a false understanding of scientific evidence against cultural knowledge. This practice is unethical. Diversity needs to be recognized as the human condition, and the recognition of diversity is an obligation for better science as well as for improving people's lives.}, } @article {pmid30397120, year = {2018}, author = {Berthier, A and Vinod, M and Porez, G and Steenackers, A and Alexandre, J and Yamakawa, N and Gheeraert, C and Ploton, M and Maréchal, X and Dubois-Chevalier, J and Hovasse, A and Schaeffer-Reiss, C and Cianférani, S and Rolando, C and Bray, F and Duez, H and Eeckhoute, J and Lefebvre, T and Staels, B and Lefebvre, P}, title = {Combinatorial regulation of hepatic cytoplasmic signaling and nuclear transcriptional events by the OGT/REV-ERBα complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11033-E11042}, pmid = {30397120}, issn = {1091-6490}, mesh = {Animals ; Cell Line, Tumor ; Circadian Clocks/physiology ; Gene Expression Regulation/genetics ; Glucose/metabolism ; HEK293 Cells ; Hep G2 Cells ; Humans ; Insulin/*metabolism ; Lipid Metabolism/physiology ; Liver/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; N-Acetylglucosaminyltransferases/genetics/*metabolism ; Nuclear Receptor Subfamily 1, Group D, Member 1/genetics/*metabolism ; Phosphorylation ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Sterol Regulatory Element Binding Protein 1/*biosynthesis/genetics ; }, abstract = {The nuclear receptor REV-ERBα integrates the circadian clock with hepatic glucose and lipid metabolism by nucleating transcriptional comodulators at genomic regulatory regions. An interactomic approach identified O-GlcNAc transferase (OGT) as a REV-ERBα-interacting protein. By shielding cytoplasmic OGT from proteasomal degradation and favoring OGT activity in the nucleus, REV-ERBα cyclically increased O-GlcNAcylation of multiple cytoplasmic and nuclear proteins as a function of its rhythmically regulated expression, while REV-ERBα ligands mostly affected cytoplasmic OGT activity. We illustrate this finding by showing that REV-ERBα controls OGT-dependent activities of the cytoplasmic protein kinase AKT, an essential relay in insulin signaling, and of ten-of-eleven translocation (TET) enzymes in the nucleus. AKT phosphorylation was inversely correlated to REV-ERBα expression. REV-ERBα enhanced TET activity and DNA hydroxymethylated cytosine (5hmC) levels in the vicinity of REV-ERBα genomic binding sites. As an example, we show that the REV-ERBα/OGT complex modulates SREBP-1c gene expression throughout the fasting/feeding periods by first repressing AKT phosphorylation and by epigenomically priming the Srebf1 promoter for a further rapid response to insulin. Conclusion: REV-ERBα regulates cytoplasmic and nuclear OGT-controlled processes that integrate at the hepatic SREBF1 locus to control basal and insulin-induced expression of the temporally and nutritionally regulated lipogenic SREBP-1c transcript.}, } @article {pmid30397119, year = {2018}, author = {Nzinga, K and Rapp, DN and Leatherwood, C and Easterday, M and Rogers, LO and Gallagher, N and Medin, DL}, title = {Should social scientists be distanced from or engaged with the people they study?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11435-11441}, pmid = {30397119}, issn = {1091-6490}, abstract = {This commentary focuses on two important contrasts in the behavioral sciences: (i) default versus nondefault study populations, where default samples have been used disproportionately (for psychology, the default is undergraduates at major research universities), and (ii) the adoption of a distant versus close (engaged) attitude toward study samples. Previous research has shown a strong correlation between these contrasts, where default samples and distant perspectives are the norm. Distancing is sometimes seen as necessary for objectivity, and an engaged orientation is sometimes criticized as biased, advocacy research, especially if the researcher shares a social group membership with the study population (e.g., a black male researcher studying black male students). The lack of diversity in study samples has been paralleled by a lack of diversity in the researchers themselves. The salience of default samples and distancing in prior research creates potential (and presumed) risk factors for engaged research with nondefault samples. However, a distant perspective poses risks as well, and particularly so for research with nondefault populations. We suggest that engaged research can usefully encourage attention to the study context and taking the perspective of study samples, both of which are good research practices. More broadly, we argue that social and educational sciences need skepticism, interestedness, and engagement, not distancing. Fostering an engaged perspective in research may also foster a more diverse population of social scientists.}, } @article {pmid30397118, year = {2018}, author = {Lenis, TL and Hu, J and Ng, SY and Jiang, Z and Sarfare, S and Lloyd, MB and Esposito, NJ and Samuel, W and Jaworski, C and Bok, D and Finnemann, SC and Radeke, MJ and Redmond, TM and Travis, GH and Radu, RA}, title = {Expression of ABCA4 in the retinal pigment epithelium and its implications for Stargardt macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11120-E11127}, pmid = {30397118}, issn = {1091-6490}, support = {R01 EY025002/EY/NEI NIH HHS/United States ; R01 EY011713/EY/NEI NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/biosynthesis/*genetics ; Animals ; Cells, Cultured ; Disease Models, Animal ; Lipofuscin/metabolism ; Lysosomes/metabolism ; Macular Degeneration/*congenital/genetics/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Phagocytosis/immunology ; Photoreceptor Cells/*metabolism ; Retina/pathology ; Retinal Degeneration/pathology ; Retinal Pigment Epithelium/*metabolism ; Retinaldehyde/*metabolism ; Rhodopsin/metabolism ; c-Mer Tyrosine Kinase/genetics ; }, abstract = {Recessive Stargardt disease (STGD1) is an inherited blinding disorder caused by mutations in the Abca4 gene. ABCA4 is a flippase in photoreceptor outer segments (OS) that translocates retinaldehyde conjugated to phosphatidylethanolamine across OS disc membranes. Loss of ABCA4 in Abca4-/- mice and STGD1 patients causes buildup of lipofuscin in the retinal pigment epithelium (RPE) and degeneration of photoreceptors, leading to blindness. No effective treatment currently exists for STGD1. Here we show by several approaches that ABCA4 is additionally expressed in RPE cells. (i) By in situ hybridization analysis and by RNA-sequencing analysis, we show the Abca4 mRNA is expressed in human and mouse RPE cells. (ii) By quantitative immunoblotting, we show that the level of ABCA4 protein in homogenates of wild-type mouse RPE is about 1% of the level in neural retina homogenates. (iii) ABCA4 immunofluorescence is present in RPE cells of wild-type and Mertk-/- but not Abca4-/- mouse retina sections, where it colocalizes with endolysosomal proteins. To elucidate the role of ABCA4 in RPE cells, we generated a line of genetically modified mice that express ABCA4 in RPE cells but not in photoreceptors. Mice from this line on the Abca4-/- background showed partial rescue of photoreceptor degeneration and decreased lipofuscin accumulation compared with nontransgenic Abca4-/- mice. We propose that ABCA4 functions to recycle retinaldehyde released during proteolysis of rhodopsin in RPE endolysosomes following daily phagocytosis of distal photoreceptor OS. ABCA4 deficiency in the RPE may play a role in the pathogenesis of STGD1.}, } @article {pmid30397117, year = {2018}, author = {}, title = {Correction for Belsky et al., Genetic analysis of social-class mobility in five longitudinal studies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10998}, doi = {10.1073/pnas.1817958115}, pmid = {30397117}, issn = {1091-6490}, } @article {pmid30397116, year = {2018}, author = {Trinkaus, E}, title = {An abundance of developmental anomalies and abnormalities in Pleistocene people.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11941-11946}, pmid = {30397116}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Bone and Bones/*abnormalities ; Fossils ; Hominidae/anatomy & histology/physiology/*psychology ; Humans ; Paleontology ; Skeleton/*abnormalities ; }, abstract = {Diverse developmental abnormalities and anomalous features are evident in the Pleistocene Homo fossil record, varying from minor but rare dental, vertebral, and carpal variants to exceptional systemic disorders. There are currently 75 documented anomalies or abnormalities from 66 individuals, spanning the Pleistocene but primarily from the Late Pleistocene Middle and Upper Paleolithic with their more complete skeletal remains. The expected probabilities of finding these variants or developmental disorders vary from <5% to <0.0001%, based on either recent human incidences or relevant Pleistocene sample distributions. Given the modest sample sizes available for the skeletal or dental elements in question, especially if the samples are appropriately limited in time and geography, the cumulative multiplicative probability of finding these developmental changes is vanishingly small. These data raise questions regarding social survival abilities, differing mortuary treatments of the biologically unusual, the role of ubiquitous stress among these Pleistocene foragers, and their levels of consanguinity. No single factor sufficiently accounts for the elevated level of these developmental variants or the low probability of finding them in the available paleontological record.}, } @article {pmid30397115, year = {2018}, author = {Brooks, BA and Hoff, K and Pandey, P}, title = {Cultural impediments to learning to cooperate: An experimental study of high- and low-caste men in rural India.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11385-11392}, pmid = {30397115}, issn = {1091-6490}, abstract = {We report experimental findings on how individuals from different cultures solve a repeated coordination game of common interest. The results overturn earlier findings that fixed pairs are almost assured to coordinate on an efficient and cooperative equilibrium. Subjects in the prior experiments were US university students, whereas the subjects in our study are men drawn from high and low castes in rural India. Most low-caste pairs quickly established an efficient and cooperative convention, but most high-caste pairs did not. The largest difference in behavior occurred when a player suffered a loss because he had tried to cooperate but his partner did not: In this situation, high-caste men were far less likely than low-caste men to continue trying to cooperate in the next period. Our interpretation is that for many high-caste men, the loss resulting from coordination failure triggered retaliation. Our results are robust to controls for education and wealth, and they hold by subcaste as well as by caste status. A survey we conducted supports the ethnographic evidence that more high-caste than low-caste men prefer to retaliate against a slight. We find no evidence that caste differences in trust or self-efficacy explain the caste gap in cooperation in our experiment. Our findings are of general interest because many societies throughout the world have cultures that lead individuals to (mis)perceive some actions as insults and to respond aggressively and dysfunctionally.}, } @article {pmid30397114, year = {2018}, author = {Rad, MS and Martingano, AJ and Ginges, J}, title = {Toward a psychology of Homo sapiens: Making psychological science more representative of the human population.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11401-11405}, pmid = {30397114}, issn = {1091-6490}, abstract = {Two primary goals of psychological science should be to understand what aspects of human psychology are universal and the way that context and culture produce variability. This requires that we take into account the importance of culture and context in the way that we write our papers and in the types of populations that we sample. However, most research published in our leading journals has relied on sampling WEIRD (Western, educated, industrialized, rich, and democratic) populations. One might expect that our scholarly work and editorial choices would by now reflect the knowledge that Western populations may not be representative of humans generally with respect to any given psychological phenomenon. However, as we show here, almost all research published by one of our leading journals, Psychological Science, relies on Western samples and uses these data in an unreflective way to make inferences about humans in general. To take us forward, we offer a set of concrete proposals for authors, journal editors, and reviewers that may lead to a psychological science that is more representative of the human condition.}, } @article {pmid30397113, year = {2018}, author = {van Leeuwen, EJC and Cronin, KA and Haun, DBM}, title = {Population-specific social dynamics in chimpanzees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11393-11400}, pmid = {30397113}, issn = {1091-6490}, abstract = {Understanding intraspecific variation in sociality is essential for characterizing the flexibility and evolution of social systems, yet its study in nonhuman animals is rare. Here, we investigated whether chimpanzees exhibit population-level differences in sociality that cannot be easily explained by differences in genetics or ecology. We compared social proximity and grooming tendencies across four semiwild populations of chimpanzees living in the same ecological environment over three consecutive years, using both linear mixed models and social network analysis. Results indicated temporally stable, population-level differences in dyadic-level sociality. Moreover, group cohesion measures capturing network characteristics beyond dyadic interactions (clustering, modularity, and social differentiation) showed population-level differences consistent with the dyadic indices. Subsequently, we explored whether the observed intraspecific variation in sociality could be attributed to cultural processes by ruling out alternative sources of variation including the influences of ecology, genetics, and differences in population demographics. We conclude that substantial variation in social behavior exists across neighboring populations of chimpanzees and that this variation is in part shaped by cultural processes.}, } @article {pmid30397112, year = {2018}, author = {Allolio, C and Magarkar, A and Jurkiewicz, P and Baxová, K and Javanainen, M and Mason, PE and Šachl, R and Cebecauer, M and Hof, M and Horinek, D and Heinz, V and Rachel, R and Ziegler, CM and Schröfel, A and Jungwirth, P}, title = {Arginine-rich cell-penetrating peptides induce membrane multilamellarity and subsequently enter via formation of a fusion pore.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11923-11928}, pmid = {30397112}, issn = {1091-6490}, mesh = {Arginine/metabolism/physiology ; Biological Transport ; Cell Membrane/metabolism ; Cell-Penetrating Peptides/*chemistry/*metabolism ; Kinetics ; Lipid Bilayers/chemistry ; Membrane Fusion/drug effects/*physiology ; Membranes/metabolism ; Molecular Dynamics Simulation ; Peptides/chemistry/physiology ; Pseudopodia/metabolism/physiology ; }, abstract = {Arginine-rich cell-penetrating peptides do not enter cells by directly passing through a lipid membrane; they instead passively enter vesicles and live cells by inducing membrane multilamellarity and fusion. The molecular picture of this penetration mode, which differs qualitatively from the previously proposed direct mechanism, is provided by molecular dynamics simulations. The kinetics of vesicle agglomeration and fusion by an iconic cell-penetrating peptide-nonaarginine-are documented via real-time fluorescence techniques, while the induction of multilamellar phases in vesicles and live cells is demonstrated by a combination of electron and fluorescence microscopies. This concert of experiments and simulations reveals that the identified passive cell penetration mechanism bears analogy to vesicle fusion induced by calcium ions, indicating that the two processes may share a common mechanistic origin.}, } @article {pmid30397111, year = {2018}, author = {Huang, M and Wang, G and Qin, J and Petranovic, D and Nielsen, J}, title = {Engineering the protein secretory pathway of Saccharomyces cerevisiae enables improved protein production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11025-E11032}, pmid = {30397111}, issn = {1091-6490}, mesh = {Endosomes/metabolism ; Golgi Apparatus/metabolism ; Histone Deacetylases/genetics ; Metabolic Engineering/*methods ; Protein Biosynthesis/*genetics ; Protein Transport/genetics ; Recombinant Proteins/genetics/*metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; Secretory Pathway/genetics/*physiology ; alpha-Amylases/*biosynthesis ; }, abstract = {Baker's yeast Saccharomyces cerevisiae is one of the most important and widely used cell factories for recombinant protein production. Many strategies have been applied to engineer this yeast for improving its protein production capacity, but productivity is still relatively low, and with increasing market demand, it is important to identify new gene targets, especially targets that have synergistic effects with previously identified targets. Despite improved protein production, previous studies rarely focused on processes associated with intracellular protein retention. Here we identified genetic modifications involved in the secretory and trafficking pathways, the histone deacetylase complex, and carbohydrate metabolic processes as targets for improving protein secretion in yeast. Especially modifications on the endosome-to-Golgi trafficking was found to effectively reduce protein retention besides increasing protein secretion. Through combinatorial genetic manipulations of several of the newly identified gene targets, we enhanced the protein production capacity of yeast by more than fivefold, and the best engineered strains could produce 2.5 g/L of a fungal α-amylase with less than 10% of the recombinant protein retained within the cells, using fed-batch cultivation.}, } @article {pmid30397110, year = {2018}, author = {Wijeratne, K and Ail, U and Brooke, R and Vagin, M and Liu, X and Fahlman, M and Crispin, X}, title = {Bulk electronic transport impacts on electron transfer at conducting polymer electrode-electrolyte interfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11899-11904}, pmid = {30397110}, issn = {1091-6490}, abstract = {Electrochemistry is an old but still flourishing field of research due to the importance of the efficiency and kinetics of electrochemical reactions in industrial processes and (bio-)electrochemical devices. The heterogeneous electron transfer from an electrode to a reactant in the solution has been well studied for metal, semiconductor, metal oxide, and carbon electrodes. For those electrode materials, there is little correlation between the electronic transport within the electrode material and the electron transfer occurring at the interface between the electrode and the solution. Here, we investigate the heterogeneous electron transfer between a conducting polymer electrode and a redox couple in an electrolyte. As a benchmark system, we use poly(3,4-ethylenedioxythiophene) (PEDOT) and the Ferro/ferricyanide redox couple in an aqueous electrolyte. We discovered a strong correlation between the electronic transport within the PEDOT electrode and the rate of electron transfer to the organometallic molecules in solution. We attribute this to a percolation-based charge transport within the polymer electrode directly involved in the electron transfer. We show the impact of this finding by optimizing an electrochemical thermogalvanic cell that transforms a heat flux into electrical power. The power generated by the cell increased by four orders of magnitude on changing the morphology and conductivity of the polymer electrode. As all conducting polymers are recognized to have percolation transport, we believe that this is a general phenomenon for this family of conductors.}, } @article {pmid30397109, year = {2018}, author = {Jacob, S and Laurent, E and Haegeman, B and Bertrand, R and Prunier, JG and Legrand, D and Cote, J and Chaine, AS and Loreau, M and Clobert, J and Schtickzelle, N}, title = {Habitat choice meets thermal specialization: Competition with specialists may drive suboptimal habitat preferences in generalists.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11988-11993}, pmid = {30397109}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Biota/*physiology ; Ciliophora/physiology ; Competitive Behavior/*physiology ; Ecosystem ; Specialization ; Species Specificity ; Temperature ; Territoriality ; Tetrahymena thermophila/*physiology ; }, abstract = {Limited dispersal is classically considered as a prerequisite for ecological specialization to evolve, such that generalists are expected to show greater dispersal propensity compared with specialists. However, when individuals choose habitats that maximize their performance instead of dispersing randomly, theory predicts dispersal with habitat choice to evolve in specialists, while generalists should disperse more randomly. We tested whether habitat choice is associated with thermal niche specialization using microcosms of the ciliate Tetrahymena thermophila, a species that performs active dispersal. We found that thermal specialists preferred optimal habitats as predicted by theory, a link that should make specialists more likely to track suitable conditions under environmental changes than expected under the random dispersal assumption. Surprisingly, generalists also performed habitat choice but with a preference for suboptimal habitats. Since this result challenges current theory, we developed a metapopulation model to understand under which circumstances such a preference for suboptimal habitats should evolve. We showed that competition between generalists and specialists may favor a preference for niche margins in generalists under environmental variability. Our results demonstrate that the behavioral dimension of dispersal-here, habitat choice-fundamentally alters our predictions of how dispersal evolve with niche specialization, making dispersal behaviors crucial for ecological forecasting facing environmental changes.}, } @article {pmid30397108, year = {2018}, author = {Gurven, MD}, title = {Broadening horizons: Sample diversity and socioecological theory are essential to the future of psychological science.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11420-11427}, pmid = {30397108}, issn = {1091-6490}, support = {R56 AG024119/AG/NIA NIH HHS/United States ; }, abstract = {The present lack of sample diversity and ecological theory in psychological science fundamentally limits generalizability and obstructs scientific progress. A focus on the role of socioecology in shaping the evolution of morphology, physiology, and behavior has not yet been widely applied toward psychology. To date, evolutionary approaches to psychology have focused more on finding universals than explaining variability. However, contrasts between small-scale, kin-based rural subsistence societies and large-scale urban, market-based populations, have not been well appreciated. Nor has the variability within high-income countries, or the socioeconomic and cultural transformations affecting even the most remote tribal populations today. Elucidating the causes and effects of such broad changes on psychology and behavior is a fundamental concern of the social sciences; expanding study participants beyond students and other convenience samples is necessary to improve understanding of flexible psychological reaction norms among and within populations. Here I highlight two examples demonstrating how socioecological variability can help explain psychological trait expression: (i) the role of environmental harshness and unpredictability on shaping time preference and related traits, such as impulsivity, vigilance, and self-efficacy; and (ii) the effects of industrialization, market integration, and niche complexity on personality structure. These cases illustrate how appropriate theory can be a powerful tool to help determine choices of diverse study populations and improve the social sciences.}, } @article {pmid30397107, year = {2018}, author = {Zigáčková, D and Vaňáčová, Š}, title = {The role of 3' end uridylation in RNA metabolism and cellular physiology.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397107}, issn = {1471-2970}, abstract = {Most eukaryotic RNAs are posttranscriptionally modified. The majority of modifications promote RNA maturation, others may regulate function and stability. The 3' terminal non-templated oligouridylation is a widespread modification affecting many cellular RNAs at some stage of their life cycle. It has diverse roles in RNA metabolism. The most prevalent is the regulation of stability and quality control. On the cellular and organismal level, it plays a critical role in a number of pathways, such as cell cycle regulation, cell death, development or viral infection. Defects in uridylation have been linked to several diseases. This review summarizes the current knowledge about the role of the 3' terminal oligo(U)-tailing in biology of various RNAs in eukaryotes and describes key factors involved in these pathways.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397106, year = {2018}, author = {Meaux, SA and Holmquist, CE and Marzluff, WF}, title = {Role of oligouridylation in normal metabolism and regulated degradation of mammalian histone mRNAs.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397106}, issn = {1471-2970}, abstract = {Metazoan replication-dependent histone mRNAs are the only known cellular mRNAs that are not polyadenylated. Histone mRNAs are present in large amounts only in S-phase cells, and their levels are coordinately regulated with the rate of DNA replication. In mammals, the stemloop at the 3' end of histone mRNA is bound to stemloop binding protein, a protein required for both synthesis and degradation of histone mRNA, and an exonuclease, 3'hExo (ERI1). Histone mRNAs are rapidly degraded when DNA synthesis is inhibited in S-phase cells and at the end of S-phase. Upf1 is also required for rapid degradation of histone mRNA as is the S-phase checkpoint. We report that Smg1 is required for histone mRNA degradation when DNA replication is inhibited, suggesting it is the PI-like kinase that activates Upf1 for histone mRNA degradation. We also show that some mutant Upf1 proteins are recruited to histone mRNAs when DNA replication is inhibited and act as dominant negative factors in histone mRNA degradation. We report that the pathway of rapid histone mRNA degradation when DNA replication is inhibited in S-phase cells that are activating the S-phase checkpoint is similar to the pathway of rapid degradation of histone mRNA at the end of S-phase.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397105, year = {2018}, author = {Tudek, A and Lloret-Llinares, M and Jensen, TH}, title = {The multitasking polyA tail: nuclear RNA maturation, degradation and export.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397105}, issn = {1471-2970}, abstract = {A polyA (pA) tail is an essential modification added to the 3' ends of a wide range of RNAs at different stages of their metabolism. Here, we describe the main sources of polyadenylation and outline their underlying biochemical interactions within the nuclei of budding yeast Saccharomyces cerevisiae, human cells and, when relevant, the fission yeast Schizosaccharomyces pombe Polyadenylation mediated by the S. cerevisiae Trf4/5 enzymes, and their human homologues PAPD5/7, typically leads to the 3'-end trimming or complete decay of non-coding RNAs. By contrast, the primary function of canonical pA polymerases (PAPs) is to produce stable and nuclear export-competent mRNAs. However, this dichotomy is becoming increasingly blurred, at least in S. pombe and human cells, where polyadenylation mediated by canonical PAPs may also result in transcript decay.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397104, year = {2018}, author = {Ugolini, I and Halic, M}, title = {Fidelity in RNA-based recognition of transposable elements.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397104}, issn = {1471-2970}, abstract = {Genomes are under constant threat of invasion by transposable elements and other genomic parasites. How can host genomes recognize these elements and target them for degradation? This requires a system that is highly adaptable, and at the same time highly specific. Current data suggest that perturbation of transcription patterns by transposon insertions could be detected by the RNAi surveillance pathway. Multiple transposon insertions might generate sufficient amounts of primal small RNAs to initiate generation of secondary small RNAs and silencing. At the same time primal small RNAs need to be constantly degraded to reduce the level of noise small RNAs below the threshold required for initiation of silencing. Failure in RNA degradation results in loss of fidelity of small RNA pathways and silencing of ectopic targets.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397103, year = {2018}, author = {Bednarek, S and Madan, V and Sikorski, PJ and Bartenschlager, R and Kowalska, J and Jemielity, J}, title = {mRNAs biotinylated within the 5' cap and protected against decapping: new tools to capture RNA-protein complexes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397103}, issn = {1471-2970}, abstract = {The 5'-terminus of eukaryotic mRNAs comprises a 7-methylguanosine cap linked to the first transcribed nucleotide via a 5'-5' triphosphate bond. This cap structure facilitates numerous interactions with molecules participating in mRNA processing, turnover and RNA translation. Here, we report the synthesis and biochemical properties of a set of biotin-labelled cap analogues modified within the triphosphate bridge and increasing mRNA stability while retaining biological activity. Successful co-transcriptional incorporation of the cap analogues allowed for the quantification of cap-dependent translation efficiency, capping efficiency and the susceptibility to decapping by Dcp2. The utility of such cap-biotinylated RNAs as molecular tool was demonstrated by ultraviolet-cross-linking and affinity capture of protein-RNA complexes. In conclusion, RNAs labelled with biotin via the 5' cap structure can be applied to a variety of biological experiments based on biotin-avidin interaction or by means of biotin-specific antibodies, including protein affinity purification, pull-down assays, in vivo visualization, cellular delivery and many others.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397102, year = {2018}, author = {Hajnsdorf, E and Kaberdin, VR}, title = {RNA polyadenylation and its consequences in prokaryotes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397102}, issn = {1471-2970}, abstract = {Post-transcriptional addition of poly(A) tails to the 3' end of RNA is one of the fundamental events controlling the functionality and fate of RNA in all kingdoms of life. Although an enzyme with poly(A)-adding activity was discovered in Escherichia coli more than 50 years ago, its existence and role in prokaryotic RNA metabolism were neglected for many years. As a result, it was not until 1992 that E. coli poly(A) polymerase I was purified to homogeneity and its gene was finally identified. Further work revealed that, similar to its role in surveillance of aberrant nuclear RNAs of eukaryotes, the addition of poly(A) tails often destabilizes prokaryotic RNAs and their decay intermediates, thus facilitating RNA turnover. Moreover, numerous studies carried out over the last three decades have shown that polyadenylation greatly contributes to the control of prokaryotic gene expression by affecting the steady-state level of diverse protein-coding and non-coding transcripts including antisense RNAs involved in plasmid copy number control, expression of toxin-antitoxin systems and bacteriophage development. Here, we review the main findings related to the discovery of polyadenylation in prokaryotes, isolation, and characterization and regulation of bacterial poly(A)-adding activities, and discuss the impact of polyadenylation on prokaryotic mRNA metabolism and gene expression.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397101, year = {2018}, author = {Charenton, C and Graille, M}, title = {mRNA decapping: finding the right structures.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397101}, issn = {1471-2970}, abstract = {In eukaryotes, the elimination of the m7GpppN mRNA cap, a process known as decapping, is a critical, largely irreversible and highly regulated step of mRNA decay that withdraws the targeted mRNAs from the pool of translatable templates. The decapping reaction is catalysed by a multi-protein complex formed by the Dcp2 catalytic subunit and its Dcp1 cofactor, a holoenzyme that is poorly active on its own and needs several accessory proteins (Lsm1-7 complex, Pat1, Edc1-2, Edc3 and/or EDC4) to be fully efficient. Here, we discuss the several crystal structures of Dcp2 domains bound to various partners (proteins or small molecules) determined in the last couple of years that have considerably improved our current understanding of how Dcp2, assisted by its various activators, is recruited to its mRNA targets and adopts its active conformation upon substrate recognition. We also describe how, over the years, elegant integrative structural biology approaches combined to biochemistry and genetics led to the identification of the correct structure of the active Dcp1-Dcp2 holoenzyme among the many available conformations trapped by X-ray crystallography.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397100, year = {2018}, author = {de Almeida, C and Scheer, H and Gobert, A and Fileccia, V and Martinelli, F and Zuber, H and Gagliardi, D}, title = {RNA uridylation and decay in plants.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397100}, issn = {1471-2970}, abstract = {RNA uridylation consists of the untemplated addition of uridines at the 3' extremity of an RNA molecule. RNA uridylation is catalysed by terminal uridylyltransferases (TUTases), which form a subgroup of the terminal nucleotidyltransferase family, to which poly(A) polymerases also belong. The key role of RNA uridylation is to regulate RNA degradation in a variety of eukaryotes, including fission yeast, plants and animals. In plants, RNA uridylation has been mostly studied in two model species, the green algae Chlamydomonas reinhardtii and the flowering plant Arabidopsis thaliana Plant TUTases target a variety of RNA substrates, differing in size and function. These RNA substrates include microRNAs (miRNAs), small interfering silencing RNAs (siRNAs), ribosomal RNAs (rRNAs), messenger RNAs (mRNAs) and mRNA fragments generated during post-transcriptional gene silencing. Viral RNAs can also get uridylated during plant infection. We describe here the evolutionary history of plant TUTases and we summarize the diverse molecular functions of uridylation during RNA degradation processes in plants. We also outline key points of future research.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397099, year = {2018}, author = {Warkocki, Z and Liudkovska, V and Gewartowska, O and Mroczek, S and Dziembowski, A}, title = {Terminal nucleotidyl transferases (TENTs) in mammalian RNA metabolism.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397099}, issn = {1471-2970}, abstract = {In eukaryotes, almost all RNA species are processed at their 3' ends and most mRNAs are polyadenylated in the nucleus by canonical poly(A) polymerases. In recent years, several terminal nucleotidyl transferases (TENTs) including non-canonical poly(A) polymerases (ncPAPs) and terminal uridyl transferases (TUTases) have been discovered. In contrast to canonical polymerases, TENTs' functions are more diverse; some, especially TUTases, induce RNA decay while others, such as cytoplasmic ncPAPs, activate translationally dormant deadenylated mRNAs. The mammalian genome encodes 11 different TENTs. This review summarizes the current knowledge about the functions and mechanisms of action of these enzymes.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397098, year = {2018}, author = {Toczydlowska-Socha, D and Zielinska, MM and Kurkowska, M and Astha, and Almeida, CF and Stefaniak, F and Purta, E and Bujnicki, JM}, title = {Human RNA cap1 methyltransferase CMTr1 cooperates with RNA helicase DHX15 to modify RNAs with highly structured 5' termini.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397098}, issn = {1471-2970}, abstract = {The 5'-cap structure, characteristic for RNA polymerase II-transcribed RNAs, plays important roles in RNA metabolism. In humans, RNA cap formation includes post-transcriptional modification of the first transcribed nucleotide by RNA cap1 methyltransferase (CMTr1). Here, we report that CMTr1 activity is hindered towards RNA substrates with highly structured 5' termini. We found that CMTr1 binds ATP-dependent RNA DHX15 helicase and that this interaction, mediated by the G-patch domain of CMTr1, has an advantageous effect on CMTr1 activity towards highly structured RNA substrates. The effect of DHX15 helicase activity is consistent with the strength of the secondary structure that has to be removed for CMTr1 to access the 5'-terminal residues in a single-stranded conformation. This is, to our knowledge, the first demonstration of the involvement of DHX15 in post-transcriptional RNA modification, and the first example of a molecular process in which DHX15 directly affects the activity of another enzyme. Our findings suggest a new mechanism underlying the regulatory role of DHX15 in the RNA capping process. RNAs with highly structured 5' termini constitute a significant fraction of the human transcriptome. Hence, CMTr1-DHX15 cooperation is likely to be important for the metabolism of RNA polymerase II-transcribed RNAs.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30397097, year = {2018}, author = {Gagliardi, D and Dziembowski, A}, title = {5' and 3' modifications controlling RNA degradation: from safeguards to executioners.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1762}, pages = {}, pmid = {30397097}, issn = {1471-2970}, abstract = {RNA degradation is a key process in the regulation of gene expression. In all organisms, RNA degradation participates in controlling coding and non-coding RNA levels in response to developmental and environmental cues. RNA degradation is also crucial for the elimination of defective RNAs. Those defective RNAs are mostly produced by 'mistakes' made by the RNA processing machinery during the maturation of functional transcripts from their precursors. The constant control of RNA quality prevents potential deleterious effects caused by the accumulation of aberrant non-coding transcripts or by the translation of defective messenger RNAs (mRNAs). Prokaryotic and eukaryotic organisms are also under the constant threat of attacks from pathogens, mostly viruses, and one common line of defence involves the ribonucleolytic digestion of the invader's RNA. Finally, mutations in components involved in RNA degradation are associated with numerous diseases in humans, and this together with the multiplicity of its roles illustrates the biological importance of RNA degradation. RNA degradation is mostly viewed as a default pathway: any functional RNA (including a successful pathogenic RNA) must be protected from the scavenging RNA degradation machinery. Yet, this protection must be temporary, and it will be overcome at one point because the ultimate fate of any cellular RNA is to be eliminated. This special issue focuses on modifications deposited at the 5' or the 3' extremities of RNA, and how these modifications control RNA stability or degradation.This article is part of the theme issue '5' and 3' modifications controlling RNA degradation'.}, } @article {pmid30396883, year = {2018}, author = {Preissler, S and Ron, D}, title = {Early Events in the Endoplasmic Reticulum Unfolded Protein Response.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a033894}, pmid = {30396883}, issn = {1943-0264}, abstract = {The physiological consequences of the unfolded protein response (UPR) are mediated by changes in gene expression. Underlying them are rapid processes involving preexisting components. We review recent insights gained into the regulation of the endoplasmic reticulum (ER) Hsp70 chaperone BiP, whose incorporation into inactive oligomers and reversible AMPylation and de-AMPylation present a first line of response to fluctuating levels of unfolded proteins. BiP activity is tied to the regulation of the UPR transducers by a recently discovered cycle of ER-localized, J protein-mediated formation of a repressive IRE1-BiP complex, whose working we contrast to an alternative model for UPR regulation that relies on direct recognition of unfolded proteins. We conclude with a discussion of mechanisms that repress messenger RNA (mRNA) translation to limit the flux of newly synthesized proteins into the ER, a rapid adaptation that does not rely on new macromolecule biosynthesis.}, } @article {pmid30396882, year = {2018}, author = {Ushioda, R and Nagata, K}, title = {Redox-Mediated Regulatory Mechanisms of Endoplasmic Reticulum Homeostasis.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a033910}, pmid = {30396882}, issn = {1943-0264}, abstract = {The endoplasmic reticulum (ER) is a dynamic organelle responsible for many cellular functions in eukaryotic cells. Proper redox conditions in the ER are necessary for the functions of many luminal pathways and the maintenance of homeostasis. The redox environment in the ER is oxidative compared with that of the cytosol, and a network of oxidoreductases centering on the protein disulfide isomerase (PDI)-Ero1α hub complex is constructed for efficient electron transfer. Although these oxidizing environments are advantageous for oxidative folding for protein maturation, electron transfer is strictly controlled by Ero1α structurally and spatially. The ER redox environment shifts to a reductive environment under certain stress conditions. In this review, we focus on the reducing reactions that maintain ER homeostasis and introduce their significance in an oxidative ER environment.}, } @article {pmid30396827, year = {2018}, author = {Varga, S}, title = {"Relaxed" natural kinds and psychiatric classification.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {72}, number = {}, pages = {49-54}, doi = {10.1016/j.shpsc.2018.10.001}, pmid = {30396827}, issn = {1879-2499}, mesh = {Humans ; Mental Disorders/*classification ; Psychiatry/*methods ; }, abstract = {This paper starts out highlighting a particular criticism that psychiatry faces and continues by investigating approaches to classification in psychiatry that operate with a "relaxed" (non-essentialist) notion of natural kind. Two accounts are examined, one by Rachel Cooper (2005; 2013) and one based on the work of Richard Boyd (1991; 1999; 2003; 2010). While these accounts do not directly pursue such a goal, the main aim is to probe whether deploying a "relaxed" notion of natural kind would be able to neutralize the criticism. While the conclusion is in the negative, the analysis raises doubts that it is possible to completely neutralize this criticism without assuming an overly simplistic view of the causal structure of the world.}, } @article {pmid30396685, year = {2019}, author = {Marshall, DJ and White, CR}, title = {Have We Outgrown the Existing Models of Growth?.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {2}, pages = {102-111}, doi = {10.1016/j.tree.2018.10.005}, pmid = {30396685}, issn = {1872-8383}, abstract = {Theories of growth have a long history in biology. Two major branches of theory (mechanistic and phenomenological) describe the dynamics of growth and explain variation in the size of organisms. Both theory branches usually assume that reproductive output scales proportionately with body size, in other words that reproductive output is isometric. A meta-analysis of hundreds of marine fishes contradicts this assumption, larger mothers reproduce disproportionately more in 95% of species studied, and patterns in other taxa suggest that reproductive hyperallometry is widespread. We argue here that reproductive hyperallometry represents a profound challenge to mechanistic theories of growth in particular, and that they should be revised accordingly. We suspect that hyperallometric reproduction drives growth trajectories in ways that are largely unanticipated by current theories.}, } @article {pmid30396371, year = {2018}, author = {Meisel, JS and Nasko, DJ and Brubach, B and Cepeda-Espinoza, V and Chopyk, J and Corrada-Bravo, H and Fedarko, M and Ghurye, J and Javkar, K and Olson, ND and Shah, N and Allard, SM and Bazinet, AL and Bergman, NH and Brown, A and Caporaso, JG and Conlan, S and DiRuggiero, J and Forry, SP and Hasan, NA and Kralj, J and Luethy, PM and Milton, DK and Ondov, BD and Preheim, S and Ratnayake, S and Rogers, SM and Rosovitz, MJ and Sakowski, EG and Schliebs, NO and Sommer, DD and Ternus, KL and Uritskiy, G and Zhang, SX and Pop, M and Treangen, TJ}, title = {Current progress and future opportunities in applications of bioinformatics for biodefense and pathogen detection: report from the Winter Mid-Atlantic Microbiome Meet-up, College Park, MD, January 10, 2018.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {197}, pmid = {30396371}, issn = {2049-2618}, support = {R01-AI-100947//National Institutes of Health/ ; U54CA143924//National Institutes of Health/ ; U54CA143925//National Institutes of Health/ ; IIS-1513615//National Science Foundation (US)/ ; 1565100//National Science Foundation (US)/ ; DEB1556574//National Science Foundation (US)/ ; W911NF-17-2-0089//Intelligence Advanced Research Projects Activity (US)/ ; R01 GM114267//National Institutes of Health (US)/ ; HSHQDC-15-C-00064//Science and Technology Directorate/ ; }, abstract = {The Mid-Atlantic Microbiome Meet-up (M3) organization brings together academic, government, and industry groups to share ideas and develop best practices for microbiome research. In January of 2018, M3 held its fourth meeting, which focused on recent advances in biodefense, specifically those relating to infectious disease, and the use of metagenomic methods for pathogen detection. Presentations highlighted the utility of next-generation sequencing technologies for identifying and tracking microbial community members across space and time. However, they also stressed the current limitations of genomic approaches for biodefense, including insufficient sensitivity to detect low-abundance pathogens and the inability to quantify viable organisms. Participants discussed ways in which the community can improve software usability and shared new computational tools for metagenomic processing, assembly, annotation, and visualization. Looking to the future, they identified the need for better bioinformatics toolkits for longitudinal analyses, improved sample processing approaches for characterizing viruses and fungi, and more consistent maintenance of database resources. Finally, they addressed the necessity of improving data standards to incentivize data sharing. Here, we summarize the presentations and discussions from the meeting, identifying the areas where microbiome analyses have improved our ability to detect and manage biological threats and infectious disease, as well as gaps of knowledge in the field that require future funding and focus.}, } @article {pmid30396369, year = {2018}, author = {Armstrong, AJS and Shaffer, M and Nusbacher, NM and Griesmer, C and Fiorillo, S and Schneider, JM and Preston Neff, C and Li, SX and Fontenot, AP and Campbell, T and Palmer, BE and Lozupone, CA}, title = {An exploration of Prevotella-rich microbiomes in HIV and men who have sex with men.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {198}, pmid = {30396369}, issn = {2049-2618}, support = {R01 DK108366//National Institute of Diabetes and Digestive and Kidney Diseases/ ; R01 DK104047//National Institute of Diabetes and Digestive and Kidney Diseases/ ; U01 HL098996//National Heart, Lung, and Blood Institute/ ; U01 HL121816//National Heart, Lung, and Blood Institute/ ; T32 AI052066//National Institute of Allergy and Infectious Diseases/ ; 2 T15 LM009451-06//U.S. National Library of Medicine/ ; }, abstract = {BACKGROUND: Gut microbiome characteristics associated with HIV infection are of intense research interest but a deep understanding has been challenged by confounding factors across studied populations. Notably, a Prevotella-rich microbiome described in HIV-infected populations is now understood to be common in men who have sex with men (MSM) regardless of HIV status, but driving factors and potential health implications are unknown.

RESULTS: Here, we further define the MSM-associated gut microbiome and describe compositional differences between the fecal microbiomes of Prevotella-rich MSM and non-MSM that may underlie observed pro-inflammatory properties. Furthermore, we show relatively subtle gut microbiome changes in HIV infection in MSM and women that include an increase in potential pathogens that is ameliorated with antiretroviral therapy (ART). Lastly, using a longitudinal cohort, we describe microbiome changes that happen after ART initiation.

CONCLUSIONS: This study provides an in-depth characterization of microbiome differences that occur in a US population infected with HIV and demonstrates the degree to which these differences may be driven by lifestyle factors, ART, and HIV infection itself. Understanding microbiome compositions that occur with sexual behaviors that are high risk for acquiring HIV and untreated and ART-treated HIV infection will guide the investigation of immune and metabolic functional implications to ultimately target the microbiome therapeutically.}, } @article {pmid30396360, year = {2018}, author = {Coleman, A and Wood, A and Bialasiewicz, S and Ware, RS and Marsh, RL and Cervin, A}, title = {The unsolved problem of otitis media in indigenous populations: a systematic review of upper respiratory and middle ear microbiology in indigenous children with otitis media.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {199}, pmid = {30396360}, issn = {2049-2618}, support = {APP1133366//National Health and Medical Research Council/ ; 1040830//National Health and Medical Research Council/ ; }, abstract = {BACKGROUND: Otitis media (OM) imposes a great burden of disease in indigenous populations around the world, despite a variety of treatment and prevention programs. Improved understanding of the pathogenesis of OM in indigenous populations is required to advance treatment and reduce prevalence. We conducted a systematic review of the literature exploring the upper airway and middle ear microbiota in relation to OM in indigenous children.

METHODS: Papers targeting microbiota in relation to OM in children < 18 years indigenous to Australia, New Zealand, North America, and Greenland were sought. MEDLINE, CINAHL, EMBASE, Cochrane Library, and Informit databases were searched using key words. Two independent reviewers screened titles, abstracts, and then full-text papers against inclusion criteria according to PRISMA guidelines.

RESULTS: Twenty-five papers considering indigenous Australian, Alaskan, and Greenlandic children were included. There were high rates of nasopharyngeal colonization with the three main otopathogens (Haemophilus influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis) in indigenous children with OM. Middle ear samples had lower rates of otopathogen detection, although detection rates increased when molecular methods were used. Pseudomonas aeruginosa and Staphylococcus aureus were commonly detected in middle ear discharge of children with chronic suppurative OM. There was a significant heterogeneity between studies, particularly in microbiological methods, which were largely limited to culture-based detection of the main otopathogens.

CONCLUSIONS: There are high rates of otopathogen colonization in indigenous children with OM. Chronic suppurative OM appears to be associated with a different microbial profile. Beyond the main otopathogens, the data are limited. Further research is required to explore the entire upper respiratory tract/middle ear microbiota in relation to OM, with the inclusion of healthy indigenous peers as controls.}, } @article {pmid30396338, year = {2018}, author = {Matheou, C and Bell, GP and Austin, P and Sousa, V and Kvajo, M}, title = {15 years of BMC Biology.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {135}, doi = {10.1186/s12915-018-0602-8}, pmid = {30396338}, issn = {1741-7007}, } @article {pmid30396330, year = {2018}, author = {Joo, S and Wang, MH and Lui, G and Lee, J and Barnas, A and Kim, E and Sudek, S and Worden, AZ and Lee, JH}, title = {Common ancestry of heterodimerizing TALE homeobox transcription factors across Metazoa and Archaeplastida.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {136}, pmid = {30396330}, issn = {1741-7007}, abstract = {BACKGROUND: Complex multicellularity requires elaborate developmental mechanisms, often based on the versatility of heterodimeric transcription factor (TF) interactions. Homeobox TFs in the TALE superclass are deeply embedded in the gene regulatory networks that orchestrate embryogenesis. Knotted-like homeobox (KNOX) TFs, homologous to animal MEIS, have been found to drive the haploid-to-diploid transition in both unicellular green algae and land plants via heterodimerization with other TALE superclass TFs, demonstrating remarkable functional conservation of a developmental TF across lineages that diverged one billion years ago. Here, we sought to delineate whether TALE-TALE heterodimerization is ancestral to eukaryotes.

RESULTS: We analyzed TALE endowment in the algal radiations of Archaeplastida, ancestral to land plants. Homeodomain phylogeny and bioinformatics analysis partitioned TALEs into two broad groups, KNOX and non-KNOX. Each group shares previously defined heterodimerization domains, plant KNOX-homology in the KNOX group and animal PBC-homology in the non-KNOX group, indicating their deep ancestry. Protein-protein interaction experiments showed that the TALEs in the two groups all participated in heterodimerization.

CONCLUSIONS: Our study indicates that the TF dyads consisting of KNOX/MEIS and PBC-containing TALEs must have evolved early in eukaryotic evolution. Based on our results, we hypothesize that in early eukaryotes, the TALE heterodimeric configuration provided transcription-on switches via dimerization-dependent subcellular localization, ensuring execution of the haploid-to-diploid transition only when the gamete fusion is correctly executed between appropriate partner gametes. The TALE switch then diversified in the several lineages that engage in a complex multicellular organization.}, } @article {pmid30396015, year = {2018}, author = {Ku, JW and Gan, YH}, title = {Modulation of bacterial virulence and fitness by host glutathione.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {8-13}, doi = {10.1016/j.mib.2018.10.004}, pmid = {30396015}, issn = {1879-0364}, abstract = {Glutathione is a low molecular weight thiol that is important for maintaining intracellular redox homeostasis. Some bacteria are able to import exogenous glutathione as a nutritional source and to counter oxidative stress. In cytosolic pathogens Burkholderia pseudomallei and Listeria monocytogenes, host glutathione regulates bacterial virulence. In B. pseudomallei, glutathione activates the membrane-bound histidine kinase sensor VirA that leads to activation of the Type VI Secretion System. In L. monocytogenes, host glutathione leads to the binding of bacterial glutathione to the master virulence regulator PrfA as an allosteric activator. Glutathione can also modulate virulence factors to control their activity by S-glutathionylation. Thus, host glutathione acts as a spacio-temporal cue for some pathogens to switch on their virulence programs at the right time and place.}, } @article {pmid30395937, year = {2019}, author = {Gaitán-Espitia, JD and González-Wevar, CA and Poulin, E and Cardenas, L}, title = {Antarctic and sub-Antarctic Nacella limpets reveal novel evolutionary characteristics of mitochondrial genomes in Patellogastropoda.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {1-7}, doi = {10.1016/j.ympev.2018.10.036}, pmid = {30395937}, issn = {1095-9513}, abstract = {Mitochondrial genomes (mitogenomes) provide valuable phylogenetic information and genome-level characters that are useful in resolving evolutionary relationships within major lineages of gastropods. However, for more than one decade, these relationships and the phylogenetic position of Patellogastropoda have been inferred based on the genomic architecture as well as the nucleotide and protein sequences of a single representative, the limpet Lottia digitalis. This mitogenome exhibits extensive rearrangements and several repetitive units that may not represent universal features for Patellogastropoda. Here, we sequenced the complete mitogenomes of three Nacella limpets, providing new insights into the dynamics of gene order and phylogenetic relationships of Patellogastropoda. Comparative analyses revealed novel gene rearrangements in Gastropoda, characterised by two main translocations that affect the KARNI and the MYCWQ clusters in Nacella limpets. Our phylogenetic reconstructions using combined sequence datasets of 13 mitochondrial protein-coding genes and two rRNAs, recovered Patellogastropoda, and Gastropoda in general, as non-monophyletic. These findings could be related to the long-branch attraction tendency of these groups, and/or taxon sampling bias. In our novel mitogenome-based phylogenetic hypothesis, L. digitalis is placed in a sister position to Bivalvia and Heterobranchia, whereas Nacella limpets are placed sister to a clade containing Caenogastropoda + Neritimorpha and Vetigastropoda + Neomphalina.}, } @article {pmid30395927, year = {2018}, author = {Gao, T and Ding, M and Yang, CH and Fan, H and Chai, Y and Li, Y}, title = {The phosphotransferase system gene ptsH plays an important role in MnSOD production, biofilm formation, swarming motility, and root colonization in Bacillus cereus 905.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.10.002}, pmid = {30395927}, issn = {1769-7123}, abstract = {The rhizosphere bacterium Bacillus cereus 905 is capable of promoting plant growth through effective colonization on plant roots. The sodA2-encoding manganese-containing superoxide dismutase (MnSOD2) is important for survival of B. cereus 905 in the wheat rhizosphere. However, the genes involved in regulating sodA2 expression and the mechanisms of rhizosphere colonization of B. cereus 905 are not well elucidated. In this study, we found that the deletion of the ptsH gene, which encodes the histidine-phosphorylatable protein (HPr), a component of the phosphotransferase system (PTS), causes a decrease of about 60% in the MnSOD2 expression. Evidences indicate that the ptsH dramatically influences resistance to oxidative stress, glucose uptake, as well as biofilm formation and swarming motility of B. cereus 905. Root colonization assay demonstrated that ΔptsH is defective in colonizing wheat roots, while complementation of the sodA2 gene could partially restore the ability in utilization of arabinose, a non-PTS sugar, and root colonization caused by the loss of the ptsH gene. In toto, based on the current findings, we propose that PtsH contributes to root colonization of B. cereus 905 through multiple indistinct mechanisms, involving PTS and uptake of PTS-sugars, up-regulation of MnSOD2 production, and promotion of biofilm formation and swarming motility.}, } @article {pmid30395805, year = {2018}, author = {Ten Tusscher, K}, title = {Of mice and plants: Comparative developmental systems biology.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.10.024}, pmid = {30395805}, issn = {1095-564X}, abstract = {Multicellular animals and plants represent independent evolutionary experiments with complex multicellular bodyplans. Differences in their life history, a mobile versus sessile lifestyle, and predominant embryonic versus postembryonic development, have led to the evolution of highly different body plans. However, also many intriguing parallels exist. Extension of the vertebrate body axis and its segmentation into somites bears striking resemblance to plant root growth and the concomittant prepatterning of lateral root competent sites. Likewise, plant shoot phyllotaxis displays similarities with vertebrate limb and digit patterning. Additionally, both plants and animals use complex signalling systems combining systemic and local signals to fine tune and coordinate organ growth across their body. Identification of these striking examples of convergent evolution provides support for the existence of general design principles: the idea that for particular patterning demands, evolution is likely to arrive at highly similar developmental patterning mechanisms. Furthermore, focussing on these parallels may aid in identifying core mechanistic principles, often obscured by the highly complex nature of multiscale patterning processes.}, } @article {pmid30395657, year = {2018}, author = {Schäffer, S and Stabentheiner, E and Shimano, S and Pfingstl, T}, title = {Leaving the tropics: The successful colonization of cold temperate regions by Dolicheremaeus dorni (Acari, Oribatida).}, journal = {Journal of zoological systematics and evolutionary research = Zeitschrift fur zoologische Systematik und Evolutionsforschung}, volume = {56}, number = {4}, pages = {505-518}, pmid = {30395657}, issn = {0947-5745}, support = {P 27843//Austrian Science Fund FWF/Austria ; }, abstract = {Species diversity is generally higher in the tropics compared to the temperate zones. The phenomenon that one species of an almost exclusively tropical living genus was able to adapt successfully to the cold northern regions is rather rare. However, the oribatid mite Dolicheremaeus dorni represents such a species and is in the focus of this study. While 180 Dolicheremaeus species are confined to the tropics and subtropics, only five species are known to occur in temperate climates and D. dorni represents the only species with a wider distribution in this climatic region. This species is distributed in Central and Southern Europe and was now recorded for the first time in Austria. A morphological and molecular genetic investigation of specimens from Austria, Poland and Croatia confirmed this distribution pattern and revealed specific geographic clades and haplotypes for each population and hence indicate low gene flow between populations. A further molecular genetic analysis of the 18S rRNA gene sequence of D. dorni confirmed its phylogenetic position within Carabodoidea. Based on record information, this species is associated with trees or tree habitats and seems to be rather a generalist than a specialist for a specific substrate (e.g., tree species) or food source.}, } @article {pmid30395254, year = {2018}, author = {Margres, MJ and Patton, A and Wray, KP and Hassinger, ATB and Ward, MJ and Lemmon, EM and Lemmon, AR and Rokyta, DR}, title = {Tipping the scales: the migration-selection balance leans toward selection in snake venoms.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy207}, pmid = {30395254}, issn = {1537-1719}, abstract = {The migration-selection interaction is the strongest determinant of whether a beneficial allele increases in frequency within a population. Results of empirical studies examining the role of gene adaptive context, however, have largely been equivocal, with examples of opposing outcomes being repeatedly documented (e.g., local adaptation with high levels of gene flow versus gene swamping). We compared neutral genomic and venom expression divergence for three sympatric pit vipers with differing ecologies to determine if and how migration-selection disequilibria result in local adaptation. We specifically tested whether neutral differentiation predicted phenotypic differentiation within an isolation-by-distance framework. The decoupling of neutral and phenotypic differentiation would indicate selection led to adaptive divergence irrespective of migration, whereas a significant relationship between neutral and venom expression differentiation would provide evidence in favor of the constraining force of gene flow. Neutral differentiation and geographic distance predicted phenotypic differentiation only in the generalist species, indicating that selection was the predominant mechanism in the migration-selection balance underlying adaptive venom evolution in both specialists. Dispersal is thought to be a stronger influence on genetic differentiation than specialization, but our results suggest the opposite. Greater specialization may lead to greater diversification rates, and extreme spatial and temporal variation in selective pressures can favor generalist phenotypes evolving under strong stabilizing selection. Our results are consistent with these expectations, suggesting that the equivocal findings of studies examining the role of gene flow in an adaptive context may be explained by ecological specialization theory.}, } @article {pmid30394871, year = {2018}, author = {Pérez-Cataluña, A and Salas-Massó, N and Figueras, MJ}, title = {Arcobacter lacus sp. nov. and Arcobacter caeni sp. nov., two novel species isolated from reclaimed water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003101}, pmid = {30394871}, issn = {1466-5034}, abstract = {Two strains (RW43-9T and RW17-10T) recovered from secondary treated wastewater from the Wastewater Treatment Plant (WWTP) in Reus (Spain) were characterized by a polyphasic taxonomic study, showing evidence that they represented two novel Arcobacter species. Based on the 16S rRNA gene for strain RW43-9T, the closest relative was Arcobacter butzleri LMG 10828T (99.9 % similarity), while for strain RW17-10T it was Arcobacter venerupis CECT 7836T (99.4 %). Additionally, multilocus phylogenetic analysis of five concatenated housekeeping genes (atpA, gyrA, gyrB, hsp60 and rpoB) showed that the two strains formed separate branches that are different from known Arcobacter species. Whole genome sequences of the two strains (RW43-9T and RW17-10T) were obtained and they were compared with those of the type strains of their nearest species. Using average nucleotide identity and in silico DNA-DNA hybridization gave values that were below 96 and 70 %, respectively. These results clearly confirm that they represent novel species. Additionally, the phenotypic characterization of the strains allowed their differentiation from other species. Therefore, the strains are proposed as representing two novel species with the names Arcobacter lacus sp. nov. (type strain RW43-9T=CECT 8994T=LMG 29062T) and Arcobacter caeni sp. nov. (type strain RW17-10T=CECT 9140T=LMG 29151T).}, } @article {pmid30394866, year = {2018}, author = {Kaminski, MA and Sobczak, A and Spolnik, G and Danikiewicz, W and Dziembowski, A and Lipinski, L}, title = {Sphingopyxis lindanitolerans sp. nov. strain WS5A3pT enriched from a pesticide disposal site.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3935-3941}, doi = {10.1099/ijsem.0.003094}, pmid = {30394866}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Hazardous Waste ; Nucleic Acid Hybridization ; *Pesticides ; Phospholipids/chemistry ; *Phylogeny ; Poland ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Sphingomonadaceae/*classification/genetics/isolation & purification ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {An aerobic, Gram-stain-negative, rod-shaped, non-motile, mesophilic soil bacterium, strain WS5A3pT, was isolated from a pesticide burial site in north-west Poland. The strain grew at 12-37 °C, at pH 8-9 and with 0-2 % (w/v) NaCl. The main fatty acids detected in WS5A3pT were summed feature 3, summed feature 8 and C16 : 0. The major respiratory quinone was Q-10 and major polar lipids were phosphatidylethanolamine, sphingoglycolipid and phosphatidylglycerol. The G+C content of the genome was 65.1 mol%. Phylogenetic pairwise distance analysis of the 16S rRNA gene placed this strain within the genus Sphingopyxis, with the highest similarity to Sphingopyxis witflariensis W-50T (98.8 %), Sphingopyxis bauzanensis BZ30T and Sphingopyxis ginsengisoli Gsoil 250T (98.3 %) and Sphingopyxis granuli NBRC 100800T (98.09 %). Genomic similarity analyses using ANIb and dDDH algorithms indicated levels of similarity of 81.44, 80.84 and 81.16 % between WS5A3pT and S. witflariensis, S. bauzanensisand S. granuli, respectively for average nucleotide identity and 25.90, 25.00 and 26.10 % for digital DNA-DNA hybridization. Based on the phylogenetic and phenotypic data, strain WS5A3pT should be considered as a representative of a novel Sphingopyxis species. The name Sphingopyxis lindanitolerans sp. nov. is proposed with the type strain WS5A3pT (=DSM 106274T=PCM 2932T).}, } @article {pmid30394865, year = {2018}, author = {Sakamoto, M and Ikeyama, N and Kunihiro, T and Iino, T and Yuki, M and Ohkuma, M}, title = {Mesosutterella multiformis gen. nov., sp. nov., a member of the family Sutterellaceae and Sutterella megalosphaeroides sp. nov., isolated from human faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3942-3950}, doi = {10.1099/ijsem.0.003096}, pmid = {30394865}, issn = {1466-5034}, mesh = {Alcaligenaceae/classification ; Bacterial Typing Techniques ; Base Composition ; Burkholderiales/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Feces/*microbiology ; Female ; Humans ; Japan ; Male ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Two novel, obligately anaerobic, Gram-stain-negative, rod or coccoid-shaped bacteria, designated strains 4NBBH2T and 6FBBBH3T, were isolated from faecal samples of a healthy Japanese woman and man. The 16S rRNA gene sequence analysis showed that these strains represent a distinct lineage within the family Sutterellaceae. Strain 4NBBH2T formed a monophyletic branch between the genera Parasutterella and Sutterella, with sequence similarity to Sutterella stercoricanis CCUG 47620T (92.6 %), followed by Sutterella wadsworthensis WAL 7877 (92.4 %), Sutterella parvirubra YIT 11816T (92.1 %) and Parasutterella secunda YIT 12071T (91.8 %). Strain 6FBBBH3T was affiliated to the genus Sutterella, with highest similarity to S. stercoricanis CCUG 47620T (97.1 %), followed by S. parvirubra YIT 11816T (96.6 %) and S. wadsworthensis WAL 7877 (95.2 %). Strains 4NBBH2T and 6FBBBH3T were asaccharolytic. Analysis of fatty acids revealed that strain 4NBBH2T could be differentiated from Sutterella species (including strain 6FBBBH3T) by the presence of a low concentration of C16 : 1ω7c. The major respiratory quinones of strain 4NBBH2T were menaquinone (MK)-6 and methylmenaquinone (MMK)-6, whereas those of strain 6FBBBH3T were MK-5 and MMK-5. The G+C content of the genomic DNA of strains 4NBBH2T and 6FBBBH3T were 56.9 and 62.8 mol%, respectively. On the basis of the collected data, strain 4NBBH2T represents a novel species in a novel genus of the family Sutterellaceae, for which the name Mesosutterella multiformis gen. nov., sp. nov. is proposed. The type strain is 4NBBH2T (=JCM 32464T=DSM 106860T). We also propose a novel Sutterella species, Sutterellamegalosphaeroides sp. nov., for strain 6FBBBH3T (=JCM 32470T=DSM 106861T).}, } @article {pmid30394664, year = {2019}, author = {Spang, A and Offre, P}, title = {Towards a systematic understanding of differences between archaeal and bacterial diversity.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {9-12}, doi = {10.1111/1758-2229.12701}, pmid = {30394664}, issn = {1758-2229}, support = {2016-03559//Swedish Research Council/ ; //NWO-I foundation of the Netherlands Organization for Scientific Research/ ; }, abstract = {In this crystal ball, we discuss emerging methodologies that can help reaching a synthesis on the biodiversity of Archaea and Bacteria and thereby inform a central enigma in microbiology, i.e. the fundamental split between these primary domains of life and the apparent lower diversity of the Archaea.}, } @article {pmid30394652, year = {2018}, author = {Borton, MA and Daly, RA and O'Banion, B and Hoyt, DW and Marcus, DN and Welch, S and Hastings, SS and Meulia, T and Wolfe, RA and Booker, AE and Sharma, S and Cole, DR and Wunch, K and Moore, JD and Darrah, TH and Wilkins, MJ and Wrighton, KC}, title = {Comparative genomics and physiology of the genus Methanohalophilus, a prevalent methanogen in hydraulically fractured shale.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4596-4611}, doi = {10.1111/1462-2920.14467}, pmid = {30394652}, issn = {1462-2920}, support = {1342701//National Science Foundation Dimensions of Biodiversity/ ; FE0024297//Department of Energy's National Energy Technology Laboratory/ ; //U.S. Department of Energy Joint Genome Institute/ ; DE-AC02-05CH11231//Office of Science of the U.S. Department of Energy/ ; }, abstract = {About 60% of natural gas production in the United States comes from hydraulic fracturing of unconventional reservoirs, such as shales or organic-rich micrites. This process inoculates and enriches for halotolerant microorganisms in these reservoirs over time, resulting in a saline ecosystem that includes methane producing archaea. Here, we survey the biogeography of methanogens across unconventional reservoirs, and report that members of genus Methanohalophilus are recovered from every hydraulically fractured unconventional reservoir sampled by metagenomics. We provide the first genomic sequencing of three isolate genomes, as well as two metagenome assembled genomes (MAGs). Utilizing six other previously sequenced isolate genomes and MAGs, we perform comparative analysis of the 11 genomes representing this genus. This genomic investigation revealed distinctions between surface and subsurface derived genomes that are consistent with constraints encountered in each environment. Genotypic differences were also uncovered between isolate genomes recovered from the same well, suggesting niche partitioning among closely related strains. These genomic substrate utilization predictions were then confirmed by physiological investigation. Fine-scale microdiversity was observed in CRISPR-Cas systems of Methanohalophilus, with genomes from geographically distinct unconventional reservoirs sharing spacers targeting the same viral population. These findings have implications for augmentation strategies resulting in enhanced biogenic methane production in hydraulically fractured unconventional reservoirs.}, } @article {pmid30394641, year = {2019}, author = {Schoeffler, M and Gaudin, AL and Ramel, F and Valette, O and Denis, Y and Hania, WB and Hirschler-Réa, A and Dolla, A}, title = {Growth of an anaerobic sulfate-reducing bacterium sustained by oxygen respiratory energy conservation after O2 -driven experimental evolution.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {360-373}, doi = {10.1111/1462-2920.14466}, pmid = {30394641}, issn = {1462-2920}, abstract = {Desulfovibrio species are representatives of microorganisms at the boundary between anaerobic and aerobic lifestyles, since they contain the enzymatic systems required for both sulfate and oxygen reduction. However, the latter has been shown to be solely a protective mechanism. By implementing the oxygen-driven experimental evolution of Desulfovibrio vulgaris Hildenborough, we have obtained strains that have evolved to grow with energy derived from oxidative phosphorylation linked to oxygen reduction. We show that a few mutations are sufficient for the emergence of this phenotype and reveal two routes of evolution primarily involving either inactivation or overexpression of the gene encoding heterodisulfide reductase. We propose that the oxygen respiration for energy conservation that sustains the growth of the O2 -evolved strains is associated with a rearrangement of metabolite fluxes, especially NAD+ /NADH, leading to an optimized O2 reduction. These evolved strains are the first sulfate-reducing bacteria that exhibit a demonstrated oxygen respiratory process that enables growth.}, } @article {pmid30394639, year = {2019}, author = {Flores, C and Santos, M and Pereira, SB and Mota, R and Rossi, F and De Philippis, R and Couto, N and Karunakaran, E and Wright, PC and Oliveira, P and Tamagnini, P}, title = {The alternative sigma factor SigF is a key player in the control of secretion mechanisms in Synechocystis sp. PCC 6803.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {343-359}, doi = {10.1111/1462-2920.14465}, pmid = {30394639}, issn = {1462-2920}, support = {POCI-01-0145-FEDER-029540//POCI/FEDER-FCT/ ; IF/00256/2015//FCT Investigator/ ; BB/M012166/1//BBSRC/ ; FP7/2007-2013//European Union Seventh Framework Programme/ ; SFRH/BD/119920/2016//Ministério da Ciência, Tecnologia e Ensino Superior/ ; SFRH/BD/99715/2014//Ministério da Ciência, Tecnologia e Ensino Superior/ ; POCI-01-0145-FEDER-007274//Fundação para a Ciência e a Tecnologia/ ; NORTE-01-0145-FEDER-000012//Fundo Europeu de Desenvolvimento Regional/ ; }, abstract = {Cyanobacterial alternative sigma factors are crucial players in environmental adaptation processes, which may involve bacterial responses related to maintenance of cell envelope and control of secretion pathways. Here, we show that the Group 3 alternative sigma factor F (SigF) plays a pleiotropic role in Synechocystis sp. PCC 6803 physiology, with a major impact on growth and secretion mechanisms, such as the production of extracellular polysaccharides, vesiculation and protein secretion. Although ΔsigF growth was significantly impaired, the production of released polysaccharides (RPS) increased threefold to fourfold compared with the wild-type. ΔsigF exhibits also impairment in formation of outer-membrane vesicles (OMVs) and pili, as well as several other cell envelope alterations. Similarly, the exoproteome composition of ΔsigF differs from the wild-type both in amount and type of proteins identified. Quantitative proteomics (iTRAQ) and an in silico analysis of SigF binding motifs revealed possible targets/pathways under SigF control. Besides changes in protein levels involved in secretion mechanisms, our results indicated that photosynthesis, central carbon metabolism and protein folding/degradation mechanisms are altered in ΔsigF. Overall, this work provided new evidences about the role of SigF on Synechocystis physiology and associates this regulatory element with classical and non-classical secretion pathways.}, } @article {pmid30394296, year = {2018}, author = {Zhu, JS and Li, YL and Yao, YS and Xie, WD}, title = {The multiple genotypes of Ophiocordyceps sinensis and the "ITS pseudogene" hypothesis.}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ympev.2018.10.034}, pmid = {30394296}, issn = {1095-9513}, } @article {pmid30393956, year = {2018}, author = {Albertson, C}, title = {Editorial.}, journal = {Evolution & development}, volume = {20}, number = {6}, pages = {191}, doi = {10.1111/ede.12274}, pmid = {30393956}, issn = {1525-142X}, mesh = {*Biological Evolution ; *Biology ; Editorial Policies ; *Periodicals as Topic ; }, } @article {pmid30393938, year = {2018}, author = {Winger, BM and Auteri, GG and Pegan, TM and Weeks, BC}, title = {A long winter for the Red Queen: rethinking the evolution of seasonal migration.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12476}, pmid = {30393938}, issn = {1469-185X}, abstract = {This paper advances an hypothesis that the primary adaptive driver of seasonal migration is maintenance of site fidelity to familiar breeding locations. We argue that seasonal migration is therefore principally an adaptation for geographic persistence when confronted with seasonality - analogous to hibernation, freeze tolerance, or other organismal adaptations to cyclically fluctuating environments. These ideas stand in contrast to traditional views that bird migration evolved as an adaptive dispersal strategy for exploiting new breeding areas and avoiding competitors. Our synthesis is supported by a large body of research on avian breeding biology that demonstrates the reproductive benefits of breeding-site fidelity. Conceptualizing migration as an adaptation for persistence places new emphasis on understanding the evolutionary trade-offs between migratory behaviour and other adaptations to fluctuating environments both within and across species. Seasonality-induced departures from breeding areas, coupled with the reproductive benefits of maintaining breeding-site fidelity, also provide a mechanism for explaining the evolution of migration that is agnostic to the geographic origin of migratory lineages (i.e. temperate or tropical). Thus, our framework reconciles much of the conflict in previous research on the historical biogeography of migratory species. Although migratory behaviour and geographic range change fluidly and rapidly in many populations, we argue that the loss of plasticity for migration via canalization is an overlooked aspect of the evolutionary dynamics of migration and helps explain the idiosyncratic distributions and migratory routes of long-distance migrants. Our synthesis, which revolves around the insight that migratory organisms travel long distances simply to stay in the same place, provides a necessary evolutionary context for understanding historical biogeographic patterns in migratory lineages as well as the ecological dynamics of migratory connectivity between breeding and non-breeding locations.}, } @article {pmid30393186, year = {2019}, author = {Rabiee, M and Sayyari, E and Mirarab, S}, title = {Multi-allele species reconstruction using ASTRAL.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {286-296}, doi = {10.1016/j.ympev.2018.10.033}, pmid = {30393186}, issn = {1095-9513}, abstract = {Genome-wide phylogeny reconstruction is becoming increasingly common, and one driving factor behind these phylogenomic studies is the promise that the potential discordance between gene trees and the species tree can be modeled. Incomplete lineage sorting is one cause of discordance that bridges population genetic and phylogenetic processes. ASTRAL is a species tree reconstruction method that seeks to find the tree with minimum quartet distance to an input set of inferred gene trees. However, the published ASTRAL algorithm only works with one sample per species. To account for polymorphisms in present-day species, one can sample multiple individuals per species to create multi-allele datasets. Here, we introduce how ASTRAL can handle multi-allele datasets. We show that the quartet-based optimization problem extends naturally, and we introduce heuristic methods for building the search space specifically for the case of multi-individual datasets. We study the accuracy and scalability of the multi-individual version of ASTRAL-III using extensive simulation studies and compare it to NJst, the only other scalable method that can handle these datasets. We do not find strong evidence that using multiple individuals dramatically improves accuracy. When we study the trade-off between sampling more genes versus more individuals, we find that sampling more genes is more effective than sampling more individuals, even under conditions that we study where trees are shallow (median length: ≈1Ne) and ILS is extremely high.}, } @article {pmid30393185, year = {2019}, author = {Liu, J and Guo, X and Chen, D and Li, J and Yue, B and Zeng, X}, title = {Diversification and historical demography of the rapid racerunner (Eremias velox) in relation to geological history and Pleistocene climatic oscillations in arid Central Asia.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {244-258}, doi = {10.1016/j.ympev.2018.10.029}, pmid = {30393185}, issn = {1095-9513}, abstract = {Late Cenozoic stepwise aridification has transformed Central Asia into an arid environment, and the Pleistocene climatic oscillations exerted further ecological impact. Therefore, both aridification and glaciation would have considerably influenced the evolution of many midlatitude species in arid Central Asia (ACA). However, strong biotic evidence supporting this role is still lacking. Here, we test this perspective using a phylogeographic study of Eremias velox, which is an arid-adapted lizard, across ACA using sequences from mitochondrial cytochrome b and 12S rRNA genes. Phylogenetic analyses of the concatenated data, including 595 specimens from 107 localities, revealed ten geographically correlated lineages that diverged by 1.1-15.4% for the cytochrome b gene and 1.0-10.3% for the 12S rRNA gene, which were estimated to have coalesced ∼6.23 million years ago. Ancestral area estimations suggested that E. velox originated from the Iranian Plateau and then dispersed into Central Asia. The intensification of aridification across Central Asia during the Late Pliocene may have facilitated the rapid radiation of this arid-adapted lizard throughout this vast territory. Subsequently, the geological events (e.g., uplift of the Kopet-Dagh, Tianshan and Greater Caucasus Mountains) and glacial oscillations during the Pleistocene triggered the progressive diversification of E. velox. The most recent common ancestor of the Caucasus-Central Asia clade was dated to approximately 2.05 Ma. Specifically, the diversification between the Caucasus clade (VI, VII) and the Central Asia clade (VIII, IX, X), and within the Central Asia clade may have been established and partially maintained by repeated transgressions of the Caspian Sea during the Pleistocene and Holocene. In contrast to demographic and/or range contractions in response to climatic changes during the Last Glacial Maximum (LGM) of the populations (Clades VI and X) from the Caucasus-Central Asia clade, mitochondrial evidence and ecological niche modeling support the signature of demographic and range expansions during the LGM for the Clade V populations (E. v. roborowskii, being endemic to the Turpan Depression). The effect of Pleistocene climatic changes on the historical demography of this arid-adapted species may be lineage-specific, depending predominantly on animal physiology and geography. Finally, we discuss the taxonomic implications, such as the appearance of the Turkmenistan populations as a distinct species, and E. v. roborowskii deserving a full species status.}, } @article {pmid30393184, year = {2019}, author = {Kennedy, M and Seneviratne, SS and Rawlence, NJ and Ratnayake, S and Spencer, HG}, title = {The phylogenetic placement of the enigmatic Indian Cormorant, Phalacrocorax fuscicollis (Phalacrocoracidae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {227-232}, doi = {10.1016/j.ympev.2018.10.019}, pmid = {30393184}, issn = {1095-9513}, abstract = {The Indian Cormorant (Phalacrocorax fuscicollis) is a common avian piscivore that occurs throughout the Indian subcontinent and east to southern Vietnam. Its evolutionary relationships, however, have remained obscure, largely because of a lack of material available for either osteological or genetic analysis. Here we show using DNA-sequence data from both nuclear and mitochondrial genes that this species is sister to the allopatric Little Black Cormorant (P. sulcirostris), which occurs from Java in the west through southern Indonesia and New Guinea to Australia and New Zealand in the south. We estimate this split to have happened 2.5-3.2 million years ago, during the late Pliocene. We also report on genetic variation within the mitochondrial control region, which suggests that this part of the genome may be useful in investigating if there is genetic structure across the geographical range of the Indian Cormorant.}, } @article {pmid30392840, year = {2018}, author = {Sharma, S and Wang, W and Stolfi, A}, title = {Single-cell transcriptome profiling of the Ciona larval brain.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.09.023}, pmid = {30392840}, issn = {1095-564X}, support = {R00 HD084814/HD/NICHD NIH HHS/United States ; }, abstract = {The tadpole-type larva of Ciona has emerged as an intriguing model system for the study of neurodevelopment. The Ciona intestinalis connectome has been recently mapped, revealing the smallest central nervous system (CNS) known in any chordate, with only 177 neurons. This minimal CNS is highly reminiscent of larger CNS of vertebrates, sharing many conserved developmental processes, anatomical compartments, neuron subtypes, and even specific neural circuits. Thus, the Ciona tadpole offers a unique opportunity to understand the development and wiring of a chordate CNS at single-cell resolution. Here we report the use of single-cell RNAseq to profile the transcriptomes of single cells isolated by fluorescence-activated cell sorting (FACS) from the whole brain of Ciona robusta (formerly intestinalis Type A) larvae. We have also compared these profiles to bulk RNAseq data from specific subsets of brain cells isolated by FACS using cell type-specific reporter plasmid expression. Taken together, these datasets have begun to reveal the compartment- and cell-specific gene expression patterns that define the organization of the Ciona larval brain.}, } @article {pmid30392839, year = {2019}, author = {Kikuchi, M and Nishimura, T and Saito, D and Shigenobu, S and Takada, R and Gutierrez-Triana, JA and Cerdán, JLM and Takada, S and Wittbrodt, J and Suyama, M and Tanaka, M}, title = {Novel components of germline sex determination acting downstream of foxl3 in medaka.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {80-89}, doi = {10.1016/j.ydbio.2018.10.019}, pmid = {30392839}, issn = {1095-564X}, abstract = {Germline sex determination is an essential process for the production of sexually dimorphic gametes. In medaka, Forkhead box L3 (foxl3) was previously identified as a germ cell-intrinsic regulator of sex determination that suppresses the initiation of spermatogenesis in female germ cells. To reveal the molecular mechanism of germline sex determination by foxl3, we conducted the following four analyses: Comparison of transcriptomes between wild-type and foxl3-mutant germ cells; epistatic analysis; identification of the FOXL3-binding motif; and ChIP-qPCR assay using a FOXL3-monoclonal antibody. We identified two candidate genes acting downstream of foxl3: Rec8a and fbxo47. It has been known that Rec8 regulates sister chromatid cohesion and Fbxo47 acts as a ubiquitin E3 ligase. These functions have not been, however, associated with sexual differentiation in germ cells. Our results uncover novel components acting downstream of foxl3, providing insights into the mechanism of germline sex determination.}, } @article {pmid30392838, year = {2019}, author = {Wang, L and Koppitch, K and Cutting, A and Dong, P and Kudtarkar, P and Zeng, J and Cameron, RA and Davidson, EH}, title = {Developmental effector gene regulation: Multiplexed strategies for functional analysis.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {68-79}, doi = {10.1016/j.ydbio.2018.10.018}, pmid = {30392838}, issn = {1095-564X}, support = {P01 HD037105/HD/NICHD NIH HHS/United States ; P40 OD010959/OD/NIH HHS/United States ; P41 HD071837/HD/NICHD NIH HHS/United States ; P41 HD095831/HD/NICHD NIH HHS/United States ; }, abstract = {The staggering complexity of the genome controls for developmental processes is revealed through massively parallel cis-regulatory analysis using new methods of perturbation and readout. The choice of combinations of these new methods is tailored to the system, question and resources at hand. Our focus is on issues that include the necessity or sufficiency of given cis-regulatory modules, cis-regulatory function in the normal spatial genomic context, and easily accessible high throughput and multiplexed analysis methods. In the sea urchin embryonic model, recombineered BACs offer new opportunities for consecutive modes of cis-regulatory analyses that answer these requirements, as we here demonstrate on a diverse suite of previously unstudied sea urchin effector genes expressed in skeletogenic cells. Positively active cis-regulatory modules were located in single Nanostring experiments per BAC containing the gene of interest, by application of our previously reported "barcode" tag vectors of which> 100 can be analyzed at one time. Computational analysis of DNA sequences that drive expression, based on the known skeletogenic regulatory state, then permitted effective identification of functional target site clusters. Deletion of these sub-regions from the parent BACs revealed module necessity, as simultaneous tests of the same regions in short constructs revealed sufficiency. Predicted functional inputs were then confirmed by site mutations, all generated and tested in multiplex formats. There emerged the simple conclusion that each effector gene utilizes a small subset of inputs from the skeletogenic GRN. These inputs may function to only adjust expression levels or in some cases necessary for expression. Since we know the GRN architecture upstream of the effector genes, we could then conceptually isolate and compare the wiring of the effector gene driver sub-circuits and identify the inputs whose removal abolish expression.}, } @article {pmid30392157, year = {2018}, author = {Syring, KE and Bosma, KJ and Oeser, JK and Shiota, M and O'Brien, RM}, title = {The Diabetes Susceptibility Gene SLC30A8 that Encodes the Zinc Transporter ZnT8 is a Pseudogene in Guinea Pigs Potentially Contributing to Low Guinea Pig Islet Zinc Content.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {613-617}, pmid = {30392157}, issn = {1432-1432}, support = {R01 DK092589/DK/NIDDK NIH HHS/United States ; R01 DK060667/DK/NIDDK NIH HHS/United States ; DK07563//National Institute of Diabetes and Digestive and Kidney Diseases/ ; DK92589//National Institute of Diabetes and Digestive and Kidney Diseases/ ; DK60667//National Institute of Diabetes and Digestive and Kidney Diseases/ ; T32 DK007563/DK/NIDDK NIH HHS/United States ; }, abstract = {In most mammals pancreatic islet beta cells have very high zinc levels that promote the crystallization and storage of insulin. Guinea pigs are unusual amongst mammals in that their islets have very low zinc content. The selectionist theory of insulin evolution proposes that low environmental zinc led to the selection of a mutation in Guinea pig insulin that negated the requirement for zinc binding. In mice deletion of the Slc30a8 gene, that encodes the zinc transporter ZnT8, markedly reduces islet zinc content. We show here that SLC30A8 is a pseudogene in Guinea pigs. We hypothesize that inactivation of the SLC30A8 gene led to low islet zinc content that allowed for the evolution of insulin that no longer bound zinc.}, } @article {pmid30391778, year = {2018}, author = {Kubori, T and Kitao, T and Nagai, H}, title = {Emerging insights into bacterial deubiquitinases.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {14-19}, doi = {10.1016/j.mib.2018.10.001}, pmid = {30391778}, issn = {1879-0364}, abstract = {Bacterial pathogens utilize eukaryotic cellular systems in various ways for their own benefits. To counteract host immune responses and survive in cells, bacteria modify host signaling pathways. For this aim, they have evolved virulence secretion systems. Bacteria-encoded effector proteins delivered via these secretion systems are the key players in bacterial pathogenesis. Ubiquitination is a post-translational modification that governs eukaryotic cellular systems. Recent studies have revealed that many bacterial effector proteins target the host ubiquitin system, often acting as ubiquitin-modulating enzymes such as ubiquitin ligases and deubiquitinases. Emerging lines of evidence have unveiled the diversity of bacterial deubiquitinases and have provided insights into the bacterial strategy to exploit the host ubiquitin system.}, } @article {pmid30391777, year = {2018}, author = {Tuli, A and Sharma, M}, title = {How to do business with lysosomes: Salmonella leads the way.}, journal = {Current opinion in microbiology}, volume = {47}, number = {}, pages = {1-7}, doi = {10.1016/j.mib.2018.10.003}, pmid = {30391777}, issn = {1879-0364}, support = {IA/I/14/2/501543//Wellcome Trust-DBT India Alliance/India ; }, abstract = {Pathogens have devised various strategies to alter the host endomembrane system towards building their replicative niche. This is aptly illustrated by Salmonella Typhimurium, whereby it remodels the host endolysosomal system to form a unique niche, also known as Salmonella-containing vacuole (SCV). Decades of research using in vitro cell-based infection studies have revealed intricate details of how Salmonella effectors target endocytic trafficking machinery of the host cell to acquire membrane and nutrients for bacterial replication. Unexpectedly, Salmonella requires host factors involved in endosome-lysosome fusion for its intravacuolar replication. Understanding how Salmonella obtains selective content from lysosomes, that is nutrients, but not active hydrolases, needs further exploration. Recent studies have described heterogeneity in the composition and pH of lysosomes, which will be highly relevant to explore, not only in the context of Salmonella infection, but also for other intracellular pathogens that interact with the endolysosomal pathway.}, } @article {pmid30391586, year = {2019}, author = {Morohoshi, A and Nakagawa, T and Nakano, S and Nagasawa, Y and Nakayama, K}, title = {The ubiquitin ligase subunit β-TrCP in Sertoli cells is essential for spermatogenesis in mice.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {178-188}, doi = {10.1016/j.ydbio.2018.10.023}, pmid = {30391586}, issn = {1095-564X}, abstract = {β-TrCP is the substrate recognition subunit of an SCF-type ubiquitin ligase. We recently showed that deletion of the genes for both β-TrCP1 and β-TrCP2 paralogs in germ cells of male mice resulted in accumulation of the transcription factor DMRT1 and spermatogenic failure, whereas systemic β-TrCP1 knockout combined with β-TrCP2 knockdown had previously been shown to lead to disruption of testicular organization and accumulation of the transcription factor SNAIL. Here we investigated β-TrCP function in Sertoli cells by generating mice with targeted deletion of the β-TrCP2 gene in Sertoli cells on a background of whole-body β-TrCP1 knockout. Loss of β-TrCP in Sertoli cells caused infertility due to a reduction in the number of mature sperm. Whereas spermatogonia were not affected, male germ cells entered meiosis prematurely and the number of round spermatids was reduced in the mutant mice. Extracts of Sertoli cells and of the testis from the mutant mice manifested accumulation of SNAIL, and expression of the SNAIL target gene for E-cadherin was down-regulated in Sertoli cells from these animals. Our results indicate that β-TrCP in Sertoli cells regulates Sertoli cell-germ cell interaction through degradation of SNAIL, with such regulation being critical for sperm development.}, } @article {pmid30391519, year = {2019}, author = {Bruyns, PV and Hanáček, P and Klak, C}, title = {Crassula, insights into an old, arid-adapted group of southern African leaf-succulents.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {35-47}, doi = {10.1016/j.ympev.2018.10.045}, pmid = {30391519}, issn = {1095-9513}, abstract = {The Crassulaceae is an important family in the Greater Cape Floristic Region of southern Africa and is the seventh largest family in the arid Succulent Karoo Biome. After the Aizoaceae it is the largest group of leaf-succulents in southern Africa. This is the first investigation of a broad selection (68%) of the ±170 species of Crassula. We used data from three chloroplast and two nuclear gene-regions, which yielded many informative characters and provided good resolution among the species. We show that only five of the 20 sections in Crassula are monophyletic. However, the clades recovered show close correlation with the two subgenera that were once recognized. Crassula contains more than 25 succulent annual species which are not closely related to each other but form early-diverging branches in each of the three major clades. One of these major clades contains far more perennial species than the others and is the greatest diversification within Crassula. This diversification mostly arose within the last 10 million years (my) and spread across much of southern Africa. Members of the smaller two major clades are often soft- and flat-leaved perennials (many with basic chromosome number x = 8, with high levels of polyploidy). Those in the largest diversification (where a basic chromosome number of x = 7 predominates) show other arid-adaptations (more highly succulent leaves with a dense covering of hairs or papillae or a smooth xeromorphic epidermis). Their flowers are also more variable in shape and bee-, moth- and butterfly-pollinated species are known among them. We establish that Crassula arose in the Greater Cape Floristic Region of southern Africa. While much of its diversity has evolved in the last 10 my, Crassula nevertheless contains species that are much older and itself arose ±46 my ago. Since all its species are succulent it is possible that they are part of an early arid-adapted flora that contributed to the Succulent Karoo Biome in the western part of southern Africa. Consequently this Biome may not be assembled only from 'young lineages' as is usually thought to be the case.}, } @article {pmid30391518, year = {2019}, author = {Simmons, MP and Sloan, DB and Springer, MS and Gatesy, J}, title = {Gene-wise resampling outperforms site-wise resampling in phylogenetic coalescence analyses.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {80-92}, doi = {10.1016/j.ympev.2018.10.001}, pmid = {30391518}, issn = {1095-9513}, abstract = {In summary ("two-step") coalescent analyses of empirical data, researchers typically apply the bootstrap to quantify branch support for clades inferred on the optimal species tree. We tested whether site-wise bootstrap analyses provide consistently more conservative support than gene-wise bootstrap analyses. We did so using data from three empirical phylogenomic studies and employed four coalescent methods (ASTRAL, MP-EST, NJst, and STAR). We demonstrate that application of site-wise bootstrapping generally resulted in gene-trees with substantial additional conflicts relative to the original data and this approach therefore cannot be relied upon to provide conservative support. Instead the site-wise bootstrap can provide high support for apparently incorrect clades. We provide a script (https://github.com/dbsloan/msc_tree_resampling) that implements gene-wise resampling, using either the bootstrap or the jackknife, for use with ASTRAL, MP-EST, NJst, and STAR. We demonstrate that the gene-wise bootstrap outperformed the site-wise bootstrap for the primary focal clades for all four coalescent methods that were applied to all three empirical studies. For summary coalescent analyses we suggest that gene-wise resampling support should be favored over gene + site or site-wise resampling when numerous genes are sampled because site-wise resampling causes substantially greater gene-tree-estimation error.}, } @article {pmid30391481, year = {2018}, author = {Edward, CJ and Kotsiopoulos, A and Harrison, STL}, title = {Low-level thiocyanate concentrations impact on iron oxidation activity and growth of Leptospirillum ferriphilum through inhibition and adaptation.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {576-581}, doi = {10.1016/j.resmic.2018.10.003}, pmid = {30391481}, issn = {1769-7123}, mesh = {Bacteria/genetics/growth & development/*metabolism ; Bacterial Proteins/genetics/metabolism ; Iron/*metabolism ; Osmotic Pressure ; Oxidation-Reduction ; Thiocyanates/analysis/*metabolism ; Waste Water/chemistry/microbiology ; }, abstract = {Leptospirillum ferriphilum is the dominant iron-oxidising bacterium in traditional microbial communities utilised in bioprocesses for gold recovery from sulfidic minerals. Ferrous iron oxidation activity and growth of unadapted and thiocyanate-adapted L. ferriphilum HT was studied in batch culture across increasing thiocyanate (SCN-) concentrations in the range 0-2 mg/L to assess the feasibility of recycling remediated cyanidation wastewaters. Thiocyanate concentrations of 1 mg/L and 1.4 mg/L induced an inhibitory effect in the unadapted culture wherein ferrous iron oxidation rate and cell growth were compromised. A substantial lag in the onset of ferrous iron oxidation occurred at concentrations above 0.5 mg/L SCN-, with no oxidation activity above 1.75 mg/L SCN-. The adapted culture, however, was uninhibited across the SCN- concentration range investigated and demonstrated a higher specific ferrous iron oxidation rate owing to reduced growth. It is postulated that SCN- exposure in the absence of adaptation induces osmotic stress. Moreover, upregulation of genes associated with the synthesis of osmo-protectants may be responsible for the preservation of activity observed in the adapted culture. As L. ferriphilum is dominant within the biooxidation tank community, evidence of sustained iron oxidation activity at low-level SCN- concentrations affirms the potential of recycling bioremediated cyanidation wastewater.}, } @article {pmid30391315, year = {2019}, author = {Homziak, NT and Breinholt, JW and Branham, MA and Storer, CG and Kawahara, AY}, title = {Anchored hybrid enrichment phylogenomics resolves the backbone of erebine moths.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {99-105}, doi = {10.1016/j.ympev.2018.10.038}, pmid = {30391315}, issn = {1095-9513}, abstract = {The subfamily Erebinae (Lepidoptera, Erebidae) includes approximately 10,000 species with many still undescribed. It is one of the most diverse clades within the moth superfamily Noctuoidea and encompasses a diversity of ecological habits. Erebine caterpillars feed on a broad range of host plants including several economically important crops. Adults possess a unique array of adaptations for predator defense, including some of the most sensitive hearing organs (tympana) across the Lepidoptera and striking wing coloration to startle visual predators. Despite the relevance of these moths to agriculture and ecological research, a robust phylogenetic framework is lacking. Here we used anchored hybrid enrichment, a relatively new approach in phylogenomics, to resolve relationships among the subfamily. Using the recently developed Lep1 anchored hybrid enrichment probe set, 658 gene fragments with an average length of 320 bp were captured from an exemplar set of 75 erebine species, representing 73 genera and 23 tribes. While the total number of erebine tribes is not firmly established, this represents at least 75% of known tribal level diversity. Anchored hybrid enrichment data were partitioned by locus and by codon position for maximum likelihood phylogenetic analysis and coalescent-based species-tree approaches. Results from our study provided strong nodal support (BP ≥ 95) for nearly all nodes in the partitioned ML tree, solidifying many relationships that were previously uncertain or moderately supported based on morphology or a smaller number of gene fragments. Likelihood analyses confidently resolved the placement of Acantholipini as a sister tribe to Sypnini and all other Erebinae. The remaining tribes were placed in a single, strongly supported clade split into two major subclades. Additionally, 25 tropical species that did not have previous tribal assignments are confidently placed on the phylogeny. Statistical comparisons with Shimodaira-Hasegawa (SH) tests found that our maximum likelihood trees were significantly more likely than alternative hypotheses. This study demonstrates the utility of anchored phylogenomics for resolving relationships within subfamilies of Lepidoptera.}, } @article {pmid30391314, year = {2019}, author = {Konecka, E and Olszanowski, Z}, title = {A new Cardinium group of bacteria found in Achipteria coleoptrata (Acari: Oribatida).}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {64-71}, doi = {10.1016/j.ympev.2018.10.043}, pmid = {30391314}, issn = {1095-9513}, abstract = {The understanding of the biology of arthropods requires an understanding of their bacterial associates. We determined the distribution of bacteria Wolbachia sp., Rickettsia sp., Cardinium sp., Spiroplasma sp., Arsenophonus sp., Hamiltonella sp., and Flavobacterium in oribatid mites (Acari: Oribatida). We identified Cardinium sp. in Achipteria coleoptrata. This is the first report of this bacterium in A. coleoptrata. Approximately 30% of the mite population was infected by Cardinium sp. The Cardinium 16S rDNA was examined for the presence of two sequences unique for this microorganism. One of them was noted in Cardinium sp. of A. coleoptrata. In the second sequence, we found nucleotide substitution in the 7th position: A instead of T. In our opinion, this demonstrated the unique nature of Cardinium sp. of A. coleoptrata. We also determined phylogenetic relationship between Cardinium sp., including the strain found in A. coleoptrata by studying the 16S rRNA and gyrB gene sequences. It revealed that Cardinium from A. coleoptrata did not cluster together with strains from groups A, B, C or D, and constituted a separate clade E. These observations make A. coleoptrata a unique Cardinium host in terms of the distinction of the strain.}, } @article {pmid30391303, year = {2018}, author = {Debarbieux, L and Forterre, P and Krupovic, M and Kutateladze, M and Prangishvili, D}, title = {Centennial celebration of the bacteriophage research.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {479-480}, doi = {10.1016/j.resmic.2018.10.001}, pmid = {30391303}, issn = {1769-7123}, mesh = {*Bacteriophages ; *Biomedical Research ; Humans ; }, } @article {pmid30391127, year = {2018}, author = {Baedke, J and Mc Manus, SF}, title = {From seconds to eons: Time scales, hierarchies, and processes in evo-devo.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {72}, number = {}, pages = {38-48}, doi = {10.1016/j.shpsc.2018.10.006}, pmid = {30391127}, issn = {1879-2499}, mesh = {*Biological Evolution ; Concept Formation ; *Developmental Biology ; *Time ; Time Factors ; }, abstract = {This paper addresses the role of time scales in conceptualizing biological hierarchies. So far, the concept of hierarchies in philosophy of science has been dominated by the idea of composition and parthood, respectively. However, this view does not exhaust the diversity of hierarchical descriptions in the biosciences. Therefore, we highlight a type of hierarchy usually overlooked by philosophers of science. It distinguishes processes based on the different time scales (i.e. rates, frequencies, and rhythms) on which they occur. These time scale hierarchies often are connected with assumptions defended in process ontology. Due to their ability to describe interlevel dynamics of various kinds, we call these hierarchies 'dynamic hierarchies.' In order to highlight and discuss their organization, explanatory roles, and epistemic virtues we focus on dynamic hierarchies in developmental biology and evolutionary developmental biology (evo-devo). In these fields, dynamic hierarchies offer crucial complementary information to descriptions of compositional hierarchies.}, } @article {pmid30391118, year = {2019}, author = {Ruzzante, L and Reijnders, MJMF and Waterhouse, RM}, title = {Of Genes and Genomes: Mosquito Evolution and Diversity.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {32-51}, doi = {10.1016/j.pt.2018.10.003}, pmid = {30391118}, issn = {1471-5007}, abstract = {Mosquitoes are widely despised for their exasperating buzzing and irritating bites, and more poignantly because, during blood-feeding, females may transmit pathogens that cause devastating diseases. However, the ability to transmit such viruses, filarial worms, or malaria parasites varies greatly amongst the ∼3500 recognised mosquito species. Applying omics technologies to sample this diversity and explore the biology underlying these variations is bringing increasingly greater resolution that enhances our understanding of mosquito evolution. Here we review the current status of mosquito omics, or 'mozomics', resources and recent advances in their applications to characterise mosquito biology and evolution, with a focus on the intersection of evolutionary and functional genomics to understand the putative links between gene and genome dynamism and mosquito diversity.}, } @article {pmid30390715, year = {2018}, author = {Khadka, P and Chapagain, G and Maharjan, G and Paudyal, P}, title = {A comparison of techniques to address the frequency of Helicobacter pylori positive dyspeptic patient.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {784}, pmid = {30390715}, issn = {1756-0500}, abstract = {OBJECTIVES: The study was aimed to compare the diagnostic techniques, for the detection of Helicobacter pylori infection, available in low-income countries, where molecular testing is not available or inaccessible to anyone.

RESULTS: Of total enrolled patient, with the mean age of 41.4 ± 13.33 years, 24 (14 female; 10 male) were diagnosed to have been infected. The diagnosis was established based upon the gold standard test [either two of three tests: Rapid Urease Test (RUT), culture and histological examinations]. Of clinical presentation, the epigastric pain (75%) was the commonest; nevertheless, the endoscopic findings had shown an equivocal specificity since the larger percentile (58.3%) reported as normal findings, in a presumed dyspepsia. Based on the premise-with calculated sensitivity, specificity, and predictive values; the accuracy order observed as histology > RUT > serology > stool antigen test, in H. pylori detection from the clinical samples. The accuracy order of the diagnostic test may vary depending upon the laboratory settings and study population. Therefore, in reference to low-income countries, the clinicians must resort any available positive test so that the supporting positive rudiments would be an ancillary in augmenting the diagnostic accuracy.}, } @article {pmid30390712, year = {2018}, author = {Efstathiou, G and Andreou, C and Tsangari, H and Dimitriadou, M and Papastavrou, E}, title = {Adaptation and validation of the Cyprus version of the Practice Environment Scale of the Nursing Work Index: a methodological study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {791}, pmid = {30390712}, issn = {1756-0500}, abstract = {OBJECTIVE: The purpose of this study was to adapt and validate the Revised Practice Environment Scale of the Nursing Work Index, to be utilized among the Cyprus nurses' population. Validated research scales are valuable tools in the hands of researchers in their attempt to recommend alterations within health care systems, especially during reform periods.

RESULTS: Internal consistency reliability of the scale was satisfactory (alpha = 0.94). Exploratory factor analysis produced a five-factor structure solution. Experts in the field provided further guidance. The findings demonstrated that the Cyprus version of the Revised Practice Environment Scale of the Nursing Work Index is a reliable and valid research instrument, however differences with previous studies on the factor structure were observed, mainly due to cultural reasons. As a valid and reliable scale, it can capture the views of nurses concerning their work environment. The Cyprus version of the Revised Practice Environment Scale of the Nursing Work Index can be used by nurse managers and policy makers to introduce changes that may improve the quality of nursing care provided and enhance the patients' satisfaction from the health system as a whole.}, } @article {pmid30390703, year = {2018}, author = {Gransjøen, AM and Wiig, S and Lysdahl, KB and Hofmann, BM}, title = {Development and conduction of an active re-implementation of the Norwegian musculoskeletal guidelines.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {785}, pmid = {30390703}, issn = {1756-0500}, abstract = {OBJECTIVE: Significant geographical variations in the use of diagnostic imaging have been demonstrated in Norway and elsewhere. Non-traumatic musculoskeletal conditions is one area where this has been demonstrated. A national musculoskeletal guideline was implemented in response by online publishing and postal dissemination in Norway in 2014 by national policy makers. The objective of our study was to develop and conduct an intervention as an active re-implementation of this guideline in one Norwegian county to investigate and facilitate guideline adherence. The development and implementation process is reported here, to facilitate understanding of the future evaluation results of this study.

RESULTS: The consolidated framework for implementation research guided the intervention development and implementation. The implementation development was also based on earlier reported success factors in combination with interviews with general practitioners and radiologists regarding facilitators and barriers to guideline adherence. A combined implementation strategy was developed, including educational meetings, shortening of the guideline and easier access. All the aspects of the implementation strategy were adapted towards general practitioners, radiological personnel and the Norwegian Labor and Welfare Administration. Sixteen educational meetings were held, and six educational videos were made for those unable to attend, or where meetings could not be held.}, } @article {pmid30390699, year = {2018}, author = {Witjaksono, F and Lukito, W and Wijaya, A and Annisa, NG and Jutamulia, J and Nurwidya, F and Simadibrata, M}, title = {The effect of breakfast with different macronutrient composition on PYY, ghrelin, and ad libitum intake 4 h after breakfast in Indonesian obese women.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {787}, pmid = {30390699}, issn = {1756-0500}, abstract = {OBJECTIVES: Gut hormones, such as PYY and ghrelin, are associated with appetite control and obesity. Protein is thought to be the most satiating nutrient and could affect the production of several gut hormones. The purpose of the current study was to find the effect of breakfast with different protein composition on PYY, ghrelin, and ad libitum intake 4 h after breakfast.

RESULTS: This clinical trial involves 22 obese women participants. Subjects were given three types of breakfast: low protein consumption (12.4% protein), medium protein (23.5% protein), and high protein (40.6% protein). PYY and ghrelin levels were measured at 0, 15, 60, 120, and 180 min after breakfast. Ad libitum meal was given 4 h after breakfast and measured after. This study found that there is no significant difference in PYY and ghrelin level at each measurement time between different type of breakfast. This study also found no significant difference of ad libitum energy intake between different type of breakfast. Trial registration ClinicalTrials.gov NCT03697486, 3 December 2018. Retrospectively registered.}, } @article {pmid30390697, year = {2018}, author = {Lindholm-Perry, AK and Kuehn, LA and McDaneld, TG and Miles, JR and Workman, AM and Chitko-McKown, CG and Keele, JW}, title = {Complete blood count data and leukocyte expression of cytokine genes and cytokine receptor genes associated with bovine respiratory disease in calves.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {786}, pmid = {30390697}, issn = {1756-0500}, abstract = {OBJECTIVE: The purpose of this study was to evaluate potential relationships between cytokine gene expression, complete blood counts (CBC) and animals that were sick or would become sick. The CBC and the transcript abundance of cytokines and their receptors expressed in leukocytes were measured from calves at two early timepoints, and again after diagnosis with bovine respiratory disease (BRD).

RESULTS: Blood was collected from calves at pre-conditioning (n = 796) and weaning (n = 791) for CBC. Blood counts were also measured for the calves with BRD (n = 13), and asymptomatic calves (n = 75) after weaning. The CBC were compared for these animals at 3 time points. At diagnosis, neutrophils were higher and basophils lower in sick animals (P < 0.05). To further characterize BRD responses, transcript abundance of 84 cytokine genes were evaluated in 5 calves with BRD and 9 asymptomatic animals at all time points. There was more data for CBC than transcript abundance; hence, animal and temporary environmental correlations between CBC and transcript abundance were exploited to improve the power of the transcript abundance data. Expression of CCL16, CXCR1, CCR1 was increased in BRD positive animals compared to controls (P-corrected < 0.1). Cytokine expression data may help to provide insight into an animal's health.}, } @article {pmid30390693, year = {2018}, author = {Sewale, Y and Hailu, G and Sintayehu, M and Moges, NA and Alebel, A}, title = {Magnitude of malnutrition and associated factors among HIV infected children attending HIV-care in three public hospitals in East and West Gojjam Zones, Amhara, Northwest, Ethiopia, 2017: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {788}, pmid = {30390693}, issn = {1756-0500}, abstract = {OBJECTIVE: The main aim of this study was to assess the magnitude of malnutrition and associated factors among HIV infected children in Amhara Regional State, and Northwest Ethiopia. This study is a result of single observation.

RESULTS: A total of 372 study participant were interviewed, of which 60.2%, 95% CI (55.90-65.60) were malnourished. Children who had good individual dietary diversity were 53% times less likely malnourished as compared to children who had fair/poor dietary diversity (AOR = 0.474, 95% CI (0.26, 0.86)). Sex of child, Age of the child, undiversified diet, comorbidity disease, oral ulcer, diarrhea and history of hospital admission were found statically significant associated with malnutrition. Magnitudes of malnutrition among HIV infected children were very high. The early detection and control progression of HIV, closely follow up to intervene this situation is highly recommended.}, } @article {pmid30390689, year = {2018}, author = {Tadesse, H and Desta, K and Kinde, S and Hassen, F and Gize, A}, title = {Clinical chemistry laboratory errors at St. Paul's Hospital Millennium Medical College (SPHMMC), Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {789}, pmid = {30390689}, issn = {1756-0500}, support = {1//Addis Ababa University/ ; }, abstract = {OBJECTIVE: This study was aimed to determine the magnitude of errors in clinical chemistry laboratory tests at different phases of the assay of clinical chemistry laboratory unit.

RESULTS: From the total 1633 clinical chemistry laboratory tests done, overall, 541 (33.1%) errors occurred which accounts that 392 (72.3%), 45 (8.3%), and 104 (19.2%) were pre analytical, analytical and post analytical phases of errors, respectively. Incomplete clinical data of patient was observed on 1185 (72.6%) of CLL tests. Name, gender, and age of patients were missed on 8 (0.5%), 190 (11.6%), and 257 (15.7%) forms of the requests, respectively. The physician's name existed only on 248 (15.2%) and signature on 1137 (69.6%) of the request forms. An essential patient data were incomplete, which needs emphasis on awareness creation. Such practice improves laboratory data interpretation and thereby prevent misdiagnose and mistreatment of patients.}, } @article {pmid30390678, year = {2018}, author = {Tufa, EG and Dake, SK and Bekru, ET and Tekle, HA and Bobe, TM and Angore, BN and Solomon, FB}, title = {Magnitude of wasting and underweight among children 6-59 months of age in Sodo Zuria District, South Ethiopia: a community based cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {790}, pmid = {30390678}, issn = {1756-0500}, abstract = {OBJECTIVES: The study aimed to determine the prevalence of wasting and underweight, and identify associated factors in Sodo Zuria district in South Ethiopia.

RESULTS: The prevalence of wasting and underweight were 11.1% and 14.0%, respectively. Wasting was significantly associated with male gender, diarrheal morbidity 2 weeks prior to the study and early initiation of complementary feeding. Predictors of underweight were diarrheal morbidity 2 weeks prior to the study and paternal illiteracy. The prevalence of wasting and underweight among under-five children is common in the study area. Diarrheal morbidity was associated with both wasting and underweight. Interventions targeting prevention of diarrheal morbidity through hygienic practices and creating awareness on infant feeding practices need to be implemented in the study area.}, } @article {pmid30390635, year = {2018}, author = {Caballero-Solares, A and Xue, X and Parrish, CC and Foroutani, MB and Taylor, RG and Rise, ML}, title = {Changes in the liver transcriptome of farmed Atlantic salmon (Salmo salar) fed experimental diets based on terrestrial alternatives to fish meal and fish oil.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {796}, pmid = {30390635}, issn = {1471-2164}, support = {GAPP #6604//Genome Canada/ ; GAPP #6604//Cargill/ ; GAPP #6604//Genome Atlantic/ ; }, abstract = {BACKGROUND: Dependence on marine natural resources threatens the sustainability of Atlantic salmon aquaculture. In the present study, Atlantic salmon fed for 14 weeks with an experimental diet based on animal by-products and vegetable oil (ABP) exhibited reduced growth performance compared with others fed a fish meal/fish oil based experimental diet (MAR) and a plant protein/vegetable oil-based experimental diet (VEG). To characterize the molecular changes underlying the differences in growth performance, we conducted a 44 K microarray study of the liver transcriptome of the three dietary groups.

RESULTS: The microarray experiment identified 122 differentially expressed features (Rank Products, PFP < 10%). Based on their associated Gene Ontology terms, 46 probes were classified as metabolic and growth-relevant genes, 25 as immune-related, and 12 as related to oxidation-reduction processes. The microarray results were validated by qPCR analysis of 29 microarray-identified transcripts. Diets significantly modulated the transcription of genes involved in carbohydrate metabolism (gck and pfkfb4), cell growth and proliferation (sgk2 and htra1), apoptosis (gadd45b), lipid metabolism (fabp3, idi1, sqs), and immunity (igd, mx, ifit5, and mhcI). Hierarchical clustering and linear correlation analyses were performed to find gene expression patterns among the qPCR-analyzed transcripts, and connections between them and muscle and liver lipid composition. Overall, our results indicate that changes in the liver transcriptome and tissue lipid composition were driven by cholesterol synthesis up-regulation by ABP and VEG diets, and the lower carbohydrate intake in the ABP group. Two of the microarray-identified genes (sgk2 and htra1) might be key to explaining glucose metabolism regulation and the dietary-modulation of the immune system in fish. To evaluate the potential of these genes as predictive biomarkers, we subjected the qPCR data to a stepwise discriminant analysis. Three sets of no more than four genes were found to be able to predict, with high accuracy (67-94%), salmon growth and fatty acid composition.

CONCLUSIONS: This study provides new findings on the impact of terrestrial animal and plant products on the nutrition and health of farmed Atlantic salmon, and a new method based on gene biomarkers for potentially predicting desired phenotypes, which could help formulate superior feeds for the Atlantic salmon aquaculture industry.}, } @article {pmid30390632, year = {2018}, author = {Wahl, SE and Wyatt, BH and Turner, SD and Dickinson, AJG}, title = {Transcriptome analysis of Xenopus orofacial tissues deficient in retinoic acid receptor function.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {795}, pmid = {30390632}, issn = {1471-2164}, support = {F32 HD091977/HD/NICHD NIH HHS/United States ; R01 DE023553/DE/NIDCR NIH HHS/United States ; 1F32HD091977-01//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; 5R01DE023553-04//National Institute of Dental and Craniofacial Research/ ; }, abstract = {BACKGROUND: Development of the face and mouth is orchestrated by a large number of transcription factors, signaling pathways and epigenetic regulators. While we know many of these regulators, our understanding of how they interact with each other and implement changes in gene expression during orofacial development is still in its infancy. Therefore, this study focuses on uncovering potential cooperation between transcriptional regulators and one important signaling pathway, retinoic acid, during development of the midface.

RESULTS: Transcriptome analyses was performed on facial tissues deficient for retinoic acid receptor function at two time points in development; early (35 hpf) just after the neural crest migrates and facial tissues are specified and later (60 hpf) when the mouth has formed and facial structures begin to differentiate. Functional and network analyses revealed that retinoic acid signaling could cooperate with novel epigenetic factors and calcium-NFAT signaling during early orofacial development. At the later stage, retinoic acid may work with WNT and BMP and regulate homeobox containing transcription factors. Finally, there is an overlap in genes dysregulated in Xenopus embryos with median clefts with human genes associated with similar orofacial defects.

CONCLUSIONS: This study uncovers novel signaling pathways required for orofacial development as well as pathways that could interact with retinoic acid signaling during the formation of the face. We show that frog faces are an important tool for studying orofacial development and birth defects.}, } @article {pmid30390629, year = {2018}, author = {Mandic, M and Ramon, ML and Gerstein, AC and Gracey, AY and Richards, JG}, title = {Variable gene transcription underlies phenotypic convergence of hypoxia tolerance in sculpins.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {163}, pmid = {30390629}, issn = {1471-2148}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Animals, Wild/genetics/physiology ; Fish Proteins/chemistry/metabolism ; Hypoxia/*genetics/*physiopathology ; Perciformes/*genetics/*physiology ; Phenotype ; RNA, Messenger/genetics/metabolism ; Time Factors ; *Transcription, Genetic ; }, abstract = {BACKGROUND: The degree by which mechanisms underlying phenotypic convergence are similar among taxa depends on the number of evolutionary paths available for selection to act upon. Likelihood of convergence will be influenced by an interplay of factors such as genetic architecture, phylogenetic history and population demography. To determine if there is convergence or divergence in mechanisms underlying phenotypic similarity, we assessed whether gene transcription patterns differed among species with similar levels of hypoxia tolerance.

RESULTS: Three species of marine fish from the superfamily Cottoidea (smoothhead sculpin [Artedius lateralis], sailfin sculpin [Nautichthys oculofasciatus] and Pacific staghorn sculpin [Leptocottus armatus]), all of which have previously been shown to share the same level of hypoxia tolerance, were exposed to short-(8 h) and longer-term (72 h) hypoxia and mRNA transcripts were assessed using a custom microarray. We examined hypoxia-induced transcription patterns in metabolic and protein production pathways and found that a high proportion of genes associated with these biological processes showed significant differences among the species. Specifically, the data suggest that the smoothhead sculpin, unlike the sailfin sculpin and the Pacific staghorn sculpin, relied on amino acid degradation rather than glycolysis or fatty acid oxidation to generate ATP during hypoxia exposure. There was also variation across the species in the transcription of genes involved in protein production (e.g. mRNA processing and protein translation), such that it increased in the smoothhead sculpin, decreased in the sailfin sculpin and was variable in the Pacific staghorn sculpin.

CONCLUSIONS: Changes in metabolic and protein production pathways are part of the key responses of fishes to exposures to environmental hypoxia. Yet, species with similar overall hypoxia tolerance exhibited different transcriptional responses in these pathways, indicating flexibility and complexity of interactions in the evolution of the mechanisms underlying the hypoxia tolerance phenotype. The variation in the hypoxia-induced transcription of genes across species with similar hypoxia tolerance suggests that similar whole-animal phenotypes can emerge from divergent evolutionary paths that may affect metabolically important functions.}, } @article {pmid30390627, year = {2018}, author = {Xie, XP and Xie, YF and Liu, YT and Wang, HQ}, title = {Adaptively capturing the heterogeneity of expression for cancer biomarker identification.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {401}, pmid = {30390627}, issn = {1471-2105}, support = {61374181//National Natural Science Foundation of China/ ; 61402010//National Natural Science Foundation of China/ ; 1408085MF133//Natural Science Foundation of Anhui Province/ ; }, mesh = {Biomarkers, Tumor/*genetics ; Computer Simulation ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; *Genetic Heterogeneity ; Humans ; Models, Genetic ; Neoplasms/*genetics ; Oligonucleotide Array Sequence Analysis ; Probability ; Sequence Analysis, RNA ; Software ; Transcriptome ; }, abstract = {BACKGROUND: Identifying cancer biomarkers from transcriptomics data is of importance to cancer research. However, transcriptomics data are often complex and heterogeneous, which complicates the identification of cancer biomarkers in practice. Currently, the heterogeneity still remains a challenge for detecting subtle but consistent changes of gene expression in cancer cells.

RESULTS: In this paper, we propose to adaptively capture the heterogeneity of expression across samples in a gene regulation space instead of in a gene expression space. Specifically, we transform gene expression profiles into gene regulation profiles and mathematically formulate gene regulation probabilities (GRPs)-based statistics for characterizing differential expression of genes between tumor and normal tissues. Finally, an unbiased estimator (aGRP) of GRPs is devised that can interrogate and adaptively capture the heterogeneity of gene expression. We also derived an asymptotical significance analysis procedure for the new statistic. Since no parameter needs to be preset, aGRP is easy and friendly to use for researchers without computer programming background. We evaluated the proposed method on both simulated data and real-world data and compared with previous methods. Experimental results demonstrated the superior performance of the proposed method in exploring the heterogeneity of expression for capturing subtle but consistent alterations of gene expression in cancer.

CONCLUSIONS: Expression heterogeneity largely influences the performance of cancer biomarker identification from transcriptomics data. Models are needed that efficiently deal with the expression heterogeneity. The proposed method can be a standalone tool due to its capacity of adaptively capturing the sample heterogeneity and the simplicity in use.

SOFTWARE AVAILABILITY: The source code of aGRP can be downloaded from https://github.com/hqwang126/aGRP .}, } @article {pmid30390625, year = {2018}, author = {Cruz, CD and Shah, S and Tammela, P}, title = {Defining conditions for biofilm inhibition and eradication assays for Gram-positive clinical reference strains.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {173}, pmid = {30390625}, issn = {1471-2180}, support = {304697//Academy of Finland/ ; 277001//Academy of Finland/ ; }, abstract = {BACKGROUND: Biofilms are formed by a complex bacterial community encapsulated by a polymeric matrix, with strong adherent properties and persistent phenotype. Biofilms are considered one of the most challenging areas of modern medicine. Existing antibiotics have been developed against free-floating bacterial cells, and thus, many treatments of biofilm-related infection fail. In this study, we compared the effects of different media on biofilm growth of clinical reference strains of Staphylococci and Enterococci, including multi-drug resistant representatives. Further, we optimized the resazurin-based assay for determining the minimal biofilm inhibitory concentration (MBIC) of standard antibiotics, and evaluated its use for the determination of minimal biofilm eradication concentration (MBEC).

RESULTS: We showed that tryptic soy broth supplemented with 1% glucose was an optimal media for maximum biofilm growth of all strains tested, with an extended incubation time for Enterococci. A range of parameters were tested for the resazurin assay, including concentration, temperature and time of incubation. Using quality parameters to analyze the assay's performance, the conditions for the resazurin assay were set as follows: 4 μg/mL and 8 μg/mL, with incubation at 25 °C for 20 min and 40 min for Staphylococci and Enterococci, respectively.

CONCLUSIONS: In summary, we defined conditions for optimal biofilm growth and for standardized resazurin assay for MBIC determination against six Gram-positive clinical reference strains. We also observed that MBEC determination by the resazurin-based assay is limited due to the poor detection limit of the assay. Complementary cell counting data is needed for precise determination of MBEC.}, } @article {pmid30390624, year = {2018}, author = {Khansefid, M and Pryce, JE and Bolormaa, S and Chen, Y and Millen, CA and Chamberlain, AJ and Vander Jagt, CJ and Goddard, ME}, title = {Comparing allele specific expression and local expression quantitative trait loci and the influence of gene expression on complex trait variation in cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {793}, pmid = {30390624}, issn = {1471-2164}, abstract = {BACKGROUND: The mutations changing the expression level of a gene, or expression quantitative trait loci (eQTL), can be identified by testing the association between genetic variants and gene expression in multiple individuals (eQTL mapping), or by comparing the expression of the alleles in a heterozygous individual (allele specific expression or ASE analysis). The aims of the study were to find and compare ASE and local eQTL in 4 bovine RNA-sequencing (RNA-Seq) datasets, validate them in an independent ASE study and investigate if they are associated with complex trait variation.

RESULTS: We present a novel method for distinguishing between ASE driven by polymorphisms in cis and parent of origin effects. We found that single nucleotide polymorphisms (SNPs) driving ASE are also often local eQTL and therefore presumably cis eQTL. These SNPs often, but not always, affect gene expression in multiple tissues and, when they do, the allele increasing expression is usually the same. However, there were systematic differences between ASE and local eQTL and between tissues and breeds. We also found that SNPs significantly associated with gene expression (p < 0.001) were likely to influence some complex traits (p < 0.001), which means that some mutations influence variation in complex traits by changing the expression level of genes.

CONCLUSION: We conclude that ASE detects phenomenon that overlap with local eQTL, but there are also systematic differences between the SNPs discovered by the two methods. Some mutations influencing complex traits are actually eQTL and can be discovered using RNA-Seq including eQTL in the genes CAST, CAPN1, LCORL and LEPROTL1.}, } @article {pmid30390623, year = {2018}, author = {Portugez, S and Martin, WF and Hazkani-Covo, E}, title = {Mosaic mitochondrial-plastid insertions into the nuclear genome show evidence of both non-homologous end joining and homologous recombination.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {162}, pmid = {30390623}, issn = {1471-2148}, mesh = {Base Sequence ; Cell Nucleus/*genetics ; DNA End-Joining Repair/*genetics ; DNA, Mitochondrial/genetics ; *Genome, Plant ; Homologous Recombination/*genetics ; Mitochondria/*genetics ; *Mosaicism ; Mutagenesis, Insertional/*genetics ; Plastids/*genetics ; }, abstract = {BACKGROUND: Mitochondrial and plastid DNA fragments are continuously transferred into eukaryotic nuclear genomes, giving rise to nuclear copies of mitochondrial DNA (numts) and nuclear copies of plastid DNA (nupts). Numts and nupts are classified as simple if they are composed of a single organelle fragment or as complex if they are composed of multiple fragments. Mosaic insertions are complex insertions composed of fragments of both mitochondrial and plastid DNA. Simple numts and nupts in eukaryotes have been extensively studied, their mechanism of insertion involves non-homologous end joining (NHEJ). Mosaic insertions have been less well-studied and their mechanisms of integration are unknown.

RESULTS: Here we estimated the number of nuclear mosaic insertions (numins) in nine plant genomes. We show that numins compose up to 10% of the total nuclear insertions of organelle DNA in these plant genomes. The NHEJ hallmarks typical for numts and nupts were also identified in mosaic insertions. However, the number of identified insertions that integrated via NHEJ mechanism is underestimated, as NHEJ signatures are conserved only in recent insertions and mutationally eroded in older ones. A few complex insertions show signatures of long homology that cannot be attributed to NHEJ, a novel observation that implicates gene conversion or single strand annealing mechanisms in organelle nuclear insertions.

CONCLUSIONS: The common NHEJ signature that was identified here reveals that, in plant cells, mitochondria and plastid fragments in numins must meet during or prior to integration into the nuclear genome.}, } @article {pmid30390622, year = {2018}, author = {Grzadkowski, MR and Sendorek, DH and P'ng, C and Huang, V and Boutros, PC}, title = {A comparative study of survival models for breast cancer prognostication revisited: the benefits of multi-gene models.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {400}, pmid = {30390622}, issn = {1471-2105}, support = {New Investigator Award//Canadian Institutes of Health Research/Canada ; New Investigator Award//Terry Fox Research Institute/ ; }, mesh = {Algorithms ; Biomarkers, Tumor/metabolism ; Breast Neoplasms/*genetics ; Databases, Genetic ; Female ; Humans ; *Models, Genetic ; Prognosis ; Survival Analysis ; }, abstract = {BACKGROUND: The development of clinical -omic biomarkers for predicting patient prognosis has mostly focused on multi-gene models. However, several studies have described significant weaknesses of multi-gene biomarkers. Indeed, some high-profile reports have even indicated that multi-gene biomarkers fail to consistently outperform simple single-gene ones. Given the continual improvements in -omics technologies and the availability of larger, better-powered datasets, we revisited this "single-gene hypothesis" using new techniques and datasets.

RESULTS: By deeply sampling the population of available gene sets, we compare the intrinsic properties of single-gene biomarkers to multi-gene biomarkers in twelve different partitions of a large breast cancer meta-dataset. We show that simple multi-gene models consistently outperformed single-gene biomarkers in all twelve partitions. We found 270 multi-gene biomarkers (one per ~11,111 sampled) that always made better predictions than the best single-gene model.

CONCLUSIONS: The single-gene hypothesis for breast cancer does not appear to retain its validity in the face of improved statistical models, lower-noise genomic technology and better-powered patient cohorts. These results highlight that it is critical to revisit older hypotheses in the light of newer techniques and datasets.}, } @article {pmid30390618, year = {2018}, author = {Davis, GS and Waits, K and Nordstrom, L and Grande, H and Weaver, B and Papp, K and Horwinski, J and Koch, B and Hungate, BA and Liu, CM and Price, LB}, title = {Antibiotic-resistant Escherichia coli from retail poultry meat with different antibiotic use claims.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {174}, pmid = {30390618}, issn = {1471-2180}, support = {W81XWH-11-1-0728//U.S. Department of Defense/ ; }, abstract = {BACKGROUND: We sought to determine if the prevalence of antibiotic-resistant Escherichia coli differed across retail poultry products and among major production categories, including organic, "raised without antibiotics", and conventional.

RESULTS: We collected all available brands of retail chicken and turkey-including conventional, "raised without antibiotic", and organic products-every two weeks from January to December 2012. In total, E. coli was recovered from 91% of 546 turkey products tested and 88% of 1367 chicken products tested. The proportion of samples contaminated with E. coli was similar across all three production categories. Resistance prevalence varied by meat type and was highest among E. coli isolates from turkey for the majority of antibiotics tested. In general, production category had little effect on resistance prevalence among E. coli isolates from chicken, although resistance to gentamicin and multidrug resistance did vary. In contrast, resistance prevalence was significantly higher for 6 of the antibiotics tested-and multidrug resistance-among isolates from conventional turkey products when compared to those labelled organic or "raised without antibiotics". E. coli isolates from chicken varied strongly in resistance prevalence among different brands within each production category.

CONCLUSION: The high prevalence of resistance among E. coli isolates from conventionally-raised turkey meat suggests greater antimicrobial use in conventional turkey production as compared to "raised without antibiotics" and organic systems. However, among E. coli from chicken meat, resistance prevalence was more strongly linked to brand than to production category, which could be caused by brand-level differences during production and/or processing, including variations in antimicrobial use.}, } @article {pmid30390617, year = {2018}, author = {Kwak, J and Park, J}, title = {What we can see from very small size sample of metagenomic sequences.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {399}, pmid = {30390617}, issn = {1471-2105}, mesh = {Base Composition/genetics ; Base Sequence ; *Metagenome ; *Metagenomics ; Molecular Sequence Annotation ; Phylogeny ; Sample Size ; }, abstract = {BACKGROUND: Since the analysis of a large number of metagenomic sequences costs heavy computing resources and takes long time, we examined a selected small part of metagenomic sequences as "sample"s of the entire full sequences, both for a mock community and for 10 different existing metagenomics case studies. A mock community with 10 bacterial strains was prepared, and their mixed genome were sequenced by Hiseq. The hits of BLAST search for reference genome of each strain were counted. Each of 176 different small parts selected from these sequences were also searched by BLAST and their hits were also counted, in order to compare them to the original search results from the full sequences. We also prepared small parts of sequences which were selected from 10 publicly downloadable research data of MG-RAST service, and analyzed these samples with MG-RAST.

RESULTS: Both the BLAST search tests of the mock community and the results from the publicly downloadable researches of MG-RAST show that sampling an extremely small part from sequence data is useful to estimate brief taxonomic information of the original metagenomic sequences. For 9 cases out of 10, the most annotated classes from the MG-RAST analyses of the selected partial sample sequences are the same as the ones from the originals.

CONCLUSIONS: When a researcher wants to estimate brief information of a metagenome's taxonomic distribution with less computing resources and within shorter time, the researcher can analyze a selected small part of metagenomic sequences. With this approach, we can also build a strategy to monitor metagenome samples of wider geographic area, more frequently.}, } @article {pmid30390616, year = {2018}, author = {Higareda-Almaraz, JC and Karbiener, M and Giroud, M and Pauler, FM and Gerhalter, T and Herzig, S and Scheideler, M}, title = {Norepinephrine triggers an immediate-early regulatory network response in primary human white adipocytes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {794}, pmid = {30390616}, issn = {1471-2164}, support = {FWF, P25729-B19//Austrian Science Fund/ ; }, abstract = {BACKGROUND: Norepinephrine (NE) signaling has a key role in white adipose tissue (WAT) functions, including lipolysis, free fatty acid liberation and, under certain conditions, conversion of white into brite (brown-in-white) adipocytes. However, acute effects of NE stimulation have not been described at the transcriptional network level.

RESULTS: We used RNA-seq to uncover a broad transcriptional response. The inference of protein-protein and protein-DNA interaction networks allowed us to identify a set of immediate-early genes (IEGs) with high betweenness, validating our approach and suggesting a hierarchical control of transcriptional regulation. In addition, we identified a transcriptional regulatory network with IEGs as master regulators, including HSF1 and NFIL3 as novel NE-induced IEG candidates. Moreover, a functional enrichment analysis and gene clustering into functional modules suggest a crosstalk between metabolic, signaling, and immune responses.

CONCLUSIONS: Altogether, our network biology approach explores for the first time the immediate-early systems level response of human adipocytes to acute sympathetic activation, thereby providing a first network basis of early cell fate programs and crosstalks between metabolic and transcriptional networks required for proper WAT function.}, } @article {pmid30390102, year = {2019}, author = {Huang, N and Pu, X and Zhang, J and Shen, H and Yang, Q and Wang, Z and Lin, B}, title = {In Vitro Formation of Dickeya zeae MS1 Biofilm.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {100-107}, doi = {10.1007/s00284-018-1593-y}, pmid = {30390102}, issn = {1432-0991}, support = {2015A030312002//Natural Science Foundation of Guangdong Province/ ; 2014J4500034//Guangzhou Science and Technology Projects (CN)/ ; 201515//President Foundation of the Guangdong Academy of Agricultural Sciences/ ; }, abstract = {Bacterial soft rot caused by Dickeya zeae MS1 (Erwinia chrysanthemi) is one of the most devastating banana diseases worldwide. However, knowledge of the development and ecological interactions of D. zeae MS1 biofilm is limited. Here, we visualized the development and architecture of D. zeae MS1 biofilm using confocal laser scanning microscopy, and we evaluated the ability of D. zeae MS1 to form biofilms under different environmental conditions (carbon sources, temperatures, pH levels and mineral elements) using a microtiter plate assay. We found that the development of D. zeae MS1 biofilm could be categorized into four phases and that mature biofilm consisted of a highly organized architecture of both bacterial cells and a self-produced matrix of extracellular polysaccharides. Furthermore, sucrose was the most suitable carbon source for supporting the growth of biofilm cells and that 32 °C and pH 7.0 were the most favorable of the temperatures and pH levels examined. Meanwhile, the addition of Ca2+, Fe2+, K+ and Na+ enhanced the formation of biofilm in minimal medium cultures, whereas 2.5 mM Cu2+ and Mn2+ was inhibitory. A better understanding of biofilm formation under different environmental parameters will improve our knowledge of the growth kinetics of D. zeae MS1 biofilm.}, } @article {pmid30390069, year = {2018}, author = {Théry, M and Asnacios, A}, title = {Cellular stretch reveals superelastic powers.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {192-194}, doi = {10.1038/d41586-018-07172-9}, pmid = {30390069}, issn = {1476-4687}, mesh = {Elasticity ; *Epithelium ; *Histone Deacetylase Inhibitors ; }, } @article {pmid30390068, year = {2018}, author = {Ransohoff, RM}, title = {Immune-cell crosstalk in multiple sclerosis.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {194-195}, doi = {10.1038/d41586-018-07063-z}, pmid = {30390068}, issn = {1476-4687}, } @article {pmid30390067, year = {2018}, author = {van Zuilen, MA}, title = {Proposed early signs of life not set in stone.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {190-191}, doi = {10.1038/d41586-018-06994-x}, pmid = {30390067}, issn = {1476-4687}, } @article {pmid30390058, year = {2018}, author = {Zhu, Z and Lee, PH and Chaffin, MD and Chung, W and Loh, PR and Lu, Q and Christiani, DC and Liang, L}, title = {Author Correction: A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1753}, doi = {10.1038/s41588-018-0284-8}, pmid = {30390058}, issn = {1546-1718}, abstract = {In the version of this article originally published, there were two errors in the text of the second paragraph of the Methods section. In the sentence "To identify genetic variants that contribute to doctor-diagnosed asthma and allergic diseases (detailed phenotype information described in the Supplementary Note) and link them with other conditions, we performed GWASs using phenotype measures in UK Biobank participants (N = 487,409)" the number of participants should have been 150,509. In the sentence "Thus, a total of 110,361 European descendants with high-quality genotyping and complete phenotype/covariate data were used for these analyses, including 25,685 allergic diseases subjects (hay fever/allergic rhinitis or eczema, without doctor-diagnosed asthma), 14,085 asthma subjects and 76,768 controls for the analysis" the phrase "without doctor-diagnosed asthma" should have read "some with doctor-diagnosed asthma." The errors have been corrected in the HTML and PDF versions of the article.}, } @article {pmid30390057, year = {2018}, author = {Iotchkova, V and Huang, J and Morris, JA and Jain, D and Barbieri, C and Walter, K and Min, JL and Chen, L and Astle, W and Cocca, M and Deelen, P and Elding, H and Farmaki, AE and Franklin, CS and Franberg, M and Gaunt, TR and Hofman, A and Jiang, T and Kleber, ME and Lachance, G and Luan, J and Malerba, G and Matchan, A and Mead, D and Memari, Y and Ntalla, I and Panoutsopoulou, K and Pazoki, R and Perry, JRB and Rivadeneira, F and Sabater-Lleal, M and Sennblad, B and Shin, SY and Southam, L and Traglia, M and van Dijk, F and van Leeuwen, EM and Zaza, G and Zhang, W and , and Amin, N and Butterworth, A and Chambers, JC and Dedoussis, G and Dehghan, A and Franco, OH and Franke, L and Frontini, M and Gambaro, G and Gasparini, P and Hamsten, A and Isaacs, A and Kooner, JS and Kooperberg, C and Langenberg, C and Marz, W and Scott, RA and Swertz, MA and Toniolo, D and Uitterlinden, AG and van Duijn, CM and Watkins, H and Zeggini, E and Maurano, MT and Timpson, NJ and Reiner, AP and Auer, PL and Soranzo, N}, title = {Author Correction: Discovery and refinement of genetic loci associated with cardiometabolic risk using dense imputation maps.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1752}, doi = {10.1038/s41588-018-0276-8}, pmid = {30390057}, issn = {1546-1718}, abstract = {In the version of the article published, the surname of author Aaron Isaacs is misspelled as Issacs.}, } @article {pmid30389709, year = {2018}, author = {Gibbs, EB and Kriwacki, RW}, title = {Linker histones as liquid-like glue for chromatin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11868-11870}, pmid = {30389709}, issn = {1091-6490}, mesh = {Adhesives ; Cell Nucleus ; *Chromatin ; DNA ; *Histones ; }, } @article {pmid30389708, year = {2018}, author = {Van Belleghem, JD and Bollyky, PL}, title = {Macrophages and innate immune memory against Staphylococcus skin infections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11865-11867}, pmid = {30389708}, issn = {1091-6490}, support = {R21 AI133370/AI/NIAID NIH HHS/United States ; }, mesh = {Immunity, Innate ; *Immunologic Memory ; *Macrophages ; Staphylococcus ; }, } @article {pmid30389707, year = {2018}, author = {Demers, EG and Biermann, AR and Masonjones, S and Crocker, AW and Ashare, A and Stajich, JE and Hogan, DA}, title = {Evolution of drug resistance in an antifungal-naive chronic Candida lusitaniae infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12040-12045}, pmid = {30389707}, issn = {1091-6490}, support = {P20 GM103413/GM/NIGMS NIH HHS/United States ; T32 GM008704/GM/NIGMS NIH HHS/United States ; R01 AI127548/AI/NIAID NIH HHS/United States ; F31 AI133956/AI/NIAID NIH HHS/United States ; S10 OD016290/OD/NIH HHS/United States ; R01 GM108492/GM/NIGMS NIH HHS/United States ; R01 HL122372/HL/NHLBI NIH HHS/United States ; }, mesh = {Alleles ; Antifungal Agents/*pharmacology ; Candida/*drug effects/*genetics ; Candidiasis/*drug therapy ; Chronic Disease ; Cystic Fibrosis/complications/microbiology ; Drug Resistance, Fungal ; Drug Resistance, Microbial ; Female ; Fluconazole/pharmacology ; Humans ; Microbial Sensitivity Tests ; Mutation ; Retrospective Studies ; Transcription Factors/metabolism ; }, abstract = {Management of the limited number of antimicrobials currently available requires the identification of infections that contain drug-resistant isolates and the discovery of factors that promote the evolution of drug resistance. Here, we report a single fungal infection in which we have identified numerous subpopulations that differ in their alleles of a single gene that impacts drug resistance. The diversity at this locus was markedly greater than the reported heterogeneity of alleles conferring antibiotic resistance in bacterial infections. Analysis of genomes from hundreds of Clavispora (Candida) lusitaniae isolates, through individual and pooled isolate sequencing, from a single individual with cystic fibrosis revealed at least 25 nonsynonymous mutations in MRR1, which encodes a transcription factor capable of inducing fluconazole (FLZ) resistance in Candida species. Isolates with high-activity Mrr1 variants were resistant to FLZ due to elevated expression of the MDR1-encoded efflux pump. We found that high Mrr1-regulated Mdr1 activity protected against host and bacterial factors, suggesting drug resistance can be selected for indirectly and perhaps explaining the Mrr1 heterogeneity in this individual who had no prior azole exposure. Regional analysis of C. lusitaniae populations from the upper and lower lobes of the right lung suggested intermingling of subpopulations throughout. Our retrospective characterization of sputum and lung populations by pooled sequencing found that alleles that confer FLZ resistance were a minority in each pool, possibly explaining why they were undetected before unsuccessful FLZ therapy. New susceptibility testing regimes may detect problematical drug-resistant subpopulations in heterogeneous single-species infections.}, } @article {pmid30389598, year = {2019}, author = {Myers, EA and Bryson, RW and Hansen, RW and Aardema, ML and Lazcano, D and Burbrink, FT}, title = {Exploring Chihuahuan Desert diversification in the gray-banded kingsnake, Lampropeltis alterna (Serpentes: Colubridae).}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {211-218}, doi = {10.1016/j.ympev.2018.10.031}, pmid = {30389598}, issn = {1095-9513}, abstract = {Within many biomes, the cause of phylogeographic structure remains unknown even across regions throughout North America, including within the biodiverse Chihuahuan Desert. For example, little is known about population structure or the timing of diversification of Chihuahuan endemics. This is due largely to the lack of population genomic studies within this region. We generated ultra-conserved element data for the gray-banded kingsnake (Lampropeltis alterna) to investigate lineage divergence and historical demography across the Chihuahuan Desert. We found three unique lineages corresponding to the Trans-Pecos and Mapimian biogeographic regions of the Chihuahuan Desert, and a distinct population in the Sierra Madre Occidental. Using several mutation rates to calibrate the timing of divergence among these lineages, we show that lineage divergence likely occurred during the Pleistocene, which indicates that careful consideration needs to be used when applying mutation rates to ultra-conserved elements. We suggest that biogeographic provinces within the Chihuahuan Desert may have served as allopatric refugia during climatic fluctuations of the Quaternary. This work serves as an important template for further testing biogeographic hypotheses within the region.}, } @article {pmid30389344, year = {2019}, author = {Eskildsen, TV and Ayoubi, S and Thomassen, M and Burton, M and Mandegar, MA and Conklin, BR and Jensen, CH and Andersen, DC and Sheikh, SP}, title = {MESP1 knock-down in human iPSC attenuates early vascular progenitor cell differentiation after completed primitive streak specification.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {1-7}, doi = {10.1016/j.ydbio.2018.10.020}, pmid = {30389344}, issn = {1095-564X}, abstract = {MESP1 is a key transcription factor in development of early cardiovascular tissue and it is required for induction of the cardiomyocyte (CM) gene expression program, but its role in vascular development is unclear. Here, we used inducible CRISPRi knock-down of MESP1 to analyze the molecular processes of the early differentiation stages of human induced pluripotent stem cells into mesoderm and subsequently vascular progenitor cells. We found that expression of the mesodermal marker, BRACHYURY (encoded by T) was unaffected in MESP1 knock-down cells as compared to wild type cells suggesting timely movement through the primitive streak whereas another mesodermal marker MIXL1 was slightly, but significantly decreased. In contrast, the expression of the vascular cell surface marker KDR was decreased and CD31 and CD34 expression were substantially reduced in MESP1 knock-down cells supporting inhibition or delay of vascular specification. In addition, mRNA microarray data revealed several other altered gene expressions including the EMT regulating transcription factors SNAI1 and TWIST1, which were both significantly decreased indicating that MESP1 knock-down cells are less likely to undergo EMT during vascular progenitor differentiation. Our study demonstrates that while leaving primitive streak markers unaffected, MESP1 expression is required for timely vascular progenitor specification. Thus, MESP1 expression is essential for the molecular features of early CM, EC and VSMC lineage specification.}, } @article {pmid30388264, year = {2018}, author = {Sharma, V and Hiller, M}, title = {Loss of Enzymes in the Bile Acid Synthesis Pathway Explains Differences in Bile Composition among Mammals.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3211-3217}, doi = {10.1093/gbe/evy243}, pmid = {30388264}, issn = {1759-6653}, abstract = {Bile acids are important for absorbing nutrients. Most mammals produce cholic and chenodeoxycholic bile acids. Here, we investigated genes in the bile acid synthesis pathway in four mammals that deviate from the usual mammalian bile composition. First, we show that naked-mole rats, elephants, and manatees repeatedly inactivated CYP8B1, an enzyme uniquely required for cholic acid synthesis, which explains the absence of cholic acid in these species. Second, no gene-inactivating mutations were found in any pathway gene in the rhinoceros, a species that lacks bile acids, indicating an evolutionarily recent change in its bile composition. Third, elephants and/or manatees that also lack bile acids altogether have lost additional nonessential enzymes (SLC27A5, ACOX2). Apart from uncovering genomic differences explaining deviations in bile composition, our analysis of bile acid enzymes in bile acid-lacking species suggests that essentiality prevents gene loss, while loss of pleiotropic genes is permitted if their other functions are compensated by functionally related proteins.}, } @article {pmid30388206, year = {2018}, author = {Shimizu, K and Kimura, K and Isowa, Y and Oshima, K and Ishikawa, M and Kagi, H and Kito, K and Hattori, M and Chiba, S and Endo, K}, title = {Insights into the evolution of shells and love darts of land snails revealed from their matrix proteins.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evy242}, pmid = {30388206}, issn = {1759-6653}, abstract = {Over the past decade, many skeletal matrix proteins that are possibly related to calcification have been reported in various calcifying animals. Molluscs are among the most diverse calcifying animals and some gastropods have adapted to terrestrial ecological niches. Although many shell matrix proteins have already been reported in molluscs, most reports have focused on marine molluscs, and the shell matrix proteins (SMPs) of terrestrial snails remain unclear. In addition, some terrestrial stylommatophoran snails have evolved an additional unique calcified character, called a "love dart", used for mating behavior. We identified 54 SMPs in the terrestrial snail Euhadra quaesita, and found that they contain specific domains that are widely conserved in molluscan SMPs. However, our results also suggest that some of them possibly have evolved independently by domain shuffling, domain recruitment, or gene co-option. We then identified four dart matrix proteins (DMPs), and found that two of them are the same proteins as those identified as SMPs. Our results suggest that some DMPs possibly have evolved by independent gene co-option from SMPs during dart evolution events. These results provide a new perspective on the evolution of SMPs and "love darts" in land snails.}, } @article {pmid30388027, year = {2018}, author = {Dong, M and Masuyer, G and Stenmark, P}, title = {Botulinum and Tetanus Neurotoxins.}, journal = {Annual review of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-biochem-013118-111654}, pmid = {30388027}, issn = {1545-4509}, abstract = {Botulinum neurotoxins (BoNTs) and tetanus neurotoxin (TeNT) are the most potent toxins known and cause botulism and tetanus, respectively. BoNTs are also widely utilized as therapeutic toxins. They contain three functional domains responsible for receptor-binding, membrane translocation, and proteolytic cleavage of host proteins required for synaptic vesicle exocytosis. These toxins also have distinct features: BoNTs exist within a progenitor toxin complex (PTC), which protects the toxin and facilitates its absorption in the gastrointestinal tract, whereas TeNT is uniquely transported retrogradely within motor neurons. Our increasing knowledge of these toxins has allowed the development of engineered toxins for medical uses. The discovery of new BoNTs and BoNT-like proteins provides additional tools to understand the evolution of the toxins and to engineer toxin-based therapeutics. This review summarizes the progress on our understanding of BoNTs and TeNT, focusing on the PTC, receptor recognition, new BoNT-like toxins, and therapeutic toxin engineering. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30387926, year = {2018}, author = {Faragalla, KM and Chernyshova, AM and Gallo, AJ and Thompson, GJ}, title = {From gene list to gene network: Recognizing functional connections that regulate behavioral traits.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {6-7}, pages = {317-329}, doi = {10.1002/jez.b.22829}, pmid = {30387926}, issn = {1552-5015}, support = {//Natural Sciences and Engineering Research Council (NSERC) of Canada Discovery Grant to GJT/ ; }, abstract = {The study of social breeding systems is often gene focused, and the field of insect sociobiology has been successful at assimilating tools and techniques from molecular biology. One common output from sociogenomic studies is a gene list. Gene lists are readily generated from microarray, RNA sequencing, or other molecular screens that typically aim to prioritize genes based on the differences in their expression. Gene lists, however, are often unsatisfying because the information they provide is simply tabular and does not explain how genes interact with each other, or how genetic interactions change in real time under social or environmental circumstances. Here, we promote a view that is relatively common to molecular systems biology, where gene lists are converted into gene networks that better describe the functional connections that regulate behavioral traits. We present a narrative related to honeybee worker sterility to show how network analysis can be used to reprioritize candidate genes based on connectivity rather than their freestanding expression values. Networks can also reveal multigene modules, motifs, clusters or other system-wide properties that might not be apparent from an ab initio list. We argue that because network analyses are not restricted to "genes" as nodes, their implementation can potentially connect multiple levels of biological organization into a single, progressively complex study system.}, } @article {pmid30387925, year = {2018}, author = {Abe, G and Li, IJ and Lee, SH and Ota, KG}, title = {A novel allele of the goldfish chdB gene: Functional evaluation and evolutionary considerations.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {6-7}, pages = {372-383}, doi = {10.1002/jez.b.22831}, pmid = {30387925}, issn = {1552-5015}, support = {106-2311-B-001-031-MY3//Ministry of Science and Technology, Taiwan/ ; JP18K06239//Japan Society for the Promotion of Science/ ; JP16K18546//Japan Society for the Promotion of Science/ ; CDA-103-L05//Academia Sinica, Career Development Award/ ; 106-2311-B-001-031-MY3//Ministry of Science and Technology/ ; }, abstract = {The twin tail of ornamental goldfish is known to be caused by a nonsense mutation in one chordin paralogue gene. Our previous molecular studies in goldfish revealed that the ancestral chordin gene was duplicated, creating the chdA and chdB genes, and the subsequent introduction of a stop codon allele in the chdA gene (chdA E127X) caused the twin-tail morphology. The chdA E127X allele was positively selected by breeders, and the allele was genetically fixed in the ornamental twin-tail goldfish population. However, little is known about the evolutionary history of the chdB paralogue, begging the question: are there the functionally distinct alleles at the chdB locus, and if so, how did they evolve? To address these questions, we conducted molecular sequencing of the chdB gene from five different goldfish strains and discovered two alleles at the chdB gene locus; the two alleles are designated chdB 1 and chdB 2 . The chdB 1 allele is the major allele and was found in all investigated goldfish strains, whereas the chdB 2 allele is minor, having only been found in one twin-tail strain. Genetic analyses further suggested that these two alleles are functionally different with regard to survivability (chdB 1 > chdB 2). These results led us to presume that in contrast to the chdA locus, the chdB locus has tended to be eliminated from the population. We also discuss how the chdB 2 allele was retained in the goldfish population, despite its disadvantageous function. This study provides empirical evidence of the long-term retention of a disadvantageous allele under domesticated conditions.}, } @article {pmid30387709, year = {2018}, author = {Liu, SW and Li, FN and Zheng, HY and Qi, X and Huang, DL and Xie, YY and Sun, CH}, title = {Planctomonas deserti gen. nov., sp. nov., a new member of the family Microbacteriaceae isolated from soil of the Taklamakan desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003095}, pmid = {30387709}, issn = {1466-5034}, abstract = {A Gram-staining-positive, aerobic, irregular coccoid- to ovoid-shaped, non-spore-forming and motile bacterium, designated strain 13S1-3T, was isolated from a soil sample from the rhizosphere of Tamarix collected in the Taklamakan desert in Xinjiang Uygur Autonomous Region, PR China. The strain was examined by a polyphasic approach to clarify its taxonomic position. Strain 13S1-3T grew optimally at 28-30 °C, pH 7.0 and with 0-1 % (w/v) NaCl. The cell-wall peptidoglycan was of the B2γ type and contained d-alanine, d-glutamic acid, glycine, d-2,4-diaminobutyric acid and l-2,4-diaminobutyric acid. Ribose, xylose, glucose and galactose were detected as cell-wall sugars. The acyl type of the muramic acid was acetyl. The predominant menaquinones were MK-12, MK-11, MK-13 and MK-10. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified glycolipids and one unidentified phospholipid. The major whole-cell fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The DNA G+C content was 70.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that 13S1-3T represented a member of the family Microbacteriaceae and showed the highest level of 16S rRNA gene sequence similarity with Frondihabitans australicus E1HC-02T (97.11 %). Phylogenetic trees revealed that 13S1-3T formed a distinct lineage with respect to closely related genera within the family Microbacteriaceae. On the basis of the results of phylogenetic, phenotypic and chemotaxonomic analyses, 13S1-3T is distinguishable from phylogenetically related genera in the family Microbacteriaceae, and represents a novel species of a new genus, for which the name Planctomonas deserti gen. nov., sp. nov. is proposed. The type strain is 13S1-3T (=KCTC 49115T=CGMCC 1.16554T).}, } @article {pmid30387708, year = {2018}, author = {Qin, J and Hu, Y and Feng, Y and Lv, X and Zong, Z}, title = {Acinetobacter sichuanensis sp. nov., recovered from hospital sewage in China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3897-3901}, doi = {10.1099/ijsem.0.003086}, pmid = {30387708}, issn = {1466-5034}, mesh = {Acinetobacter/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Genes, Bacterial ; Genotype ; *Hospitals ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; }, abstract = {A novel Acinetobacter strain, WCHAc060041T, was recovered from hospital sewage at West China Hospital in Chengdu, Sichuan Province, China. The strain was Gram-negative coccobacillus, non-spore-forming, non-motile and strictly aerobic. The genomic DNA G+C content was 37.02 mol%. The 16S rRNA and rpoB gene sequences of the strain were ≤98.2 and≤89.5 % identical to the type strains of all known Acinetobacter species, respectively. The strain formed a distinct branch based on the genus-wide comparison of whole-cell mass fingerprints generated by matrix-assisted laser desorption/ionization-time-of flight mass spectrometry. Strain WCHAc060041T was subjected to whole genome sequencing. The average nucleotide identity based on blast (ANIb) and in silico DNA-DNA hybridization (isDDH) values between strain WCHAc060041T and type strains of other Acinetobacter species were ≤82.7 and ≤26.9 %, respectively. Strain WCHAc060041T could be distinguished from all known Acinetobacter species by its ability to assimilate gentisate and levulinate, but not to citrate (Simmons'). Genotypic and phenotypic characteristics from this study indicate that strain WCHAc060041T represents a novel species of the genus Acinetobacter, for which the name Acinetobacter sichuanensis sp. nov. is proposed. The type strain is WCHAc060041T (=CCTCC AB 2018118T=GDMCC 1.1383T=KCTC 62575T).}, } @article {pmid30387707, year = {2018}, author = {Wu, W and Feng, Y and Zong, Z}, title = {Enterobacter sichuanensis sp. nov., recovered from human urine.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3922-3927}, doi = {10.1099/ijsem.0.003089}, pmid = {30387707}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Enterobacter/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Genes, Bacterial ; Humans ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Urine/*microbiology ; }, abstract = {An Enterobacter strain, WCHECL1597T, was recovered from the urine of a patient in China in 2016. Phylogenetic analysis based on its 16S rRNA gene sequence indicated the strain belongs to the genus Enterobacter, while multi-locus sequence analysis of the rpoB, gyrB, infB and atpD housekeeping genes revealed that the strain was distinct from any previously described Enterobacter species. The whole genome sequence of strain WCHECL1597T had a 79.81-91.49 % average nucleotide identity to those of type strains of all known Enterobacter species. In silico DNA-DNA hybridization values between strain WCHECL1597T and the type strains of all known Enterobacter species ranged from 22.8 to 45.2 %. The major cellular fatty acids of strain WCHECL1597T were C16 : 0, C17 : 0cyclo and C18 : 1ω7c, which are in the quantitative range of other Enterobacter species while differentiated by the relatively higher amount (12.3 %) of iso-c16 : 1 I/C14 : 0 3-OH. The genomic DNA G+C content was 55.2 mol%. Strain WCHECL1597T could be distinguished from all known Enterobacter species by its ability to ferment inositol but with a negative l-rhamnose and d-mannitol reaction. Genotypic and phenotypic characteristics from this study indicate that strain WCHECL1597T represents a novel species of the genus Enterobacter, for which the name Enterobactersichuanensis sp. nov. is proposed. The type strain is WCHECL1597T (=GDMCC1.1217T=CCTCC AB 2017104T=KCTC 52994T).}, } @article {pmid30387533, year = {2019}, author = {Gil, D and Alfonso-Iñiguez, S and Pérez-Rodríguez, L and Muriel, J and Monclús, R}, title = {Harsh conditions during early development influence telomere length in an altricial passerine: Links with oxidative stress and corticosteroids.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {111-125}, doi = {10.1111/jeb.13396}, pmid = {30387533}, issn = {1420-9101}, support = {//Universidad de Castilla-La Mancha/ ; 656522//H2020 Marie Skłodowska-Curie Actions/ ; CGL-201126318//Ministerio de Ciencia e Innovación/ ; //European Commission/ ; CGL2011-26318//Ministerio de Ciencia e Innovación/ ; BES-2012-055897//FPI/ ; BES-2009-021383//FPI/ ; //Spanish Ministry of Science and Innovation (MICINN)/ ; //University of Castilla-La Mancha/ ; //European Union's Horizon 2020 research and innovation programme/ ; 656522//Marie Skłodowska-Curie/ ; //Ayuntamiento de Soto del Real/ ; }, abstract = {Stress during early development can induce substantial long-term effects in organisms. In the case of birds, despite growth compensations, nestlings reared under harsh conditions typically show reduced survival chances in adulthood. It has been proposed that environmental early-life stressors could affect longevity via effects on telomere length, possibly mediated through oxidative stress. However, the link between these processes is not clear. In this study, we experimentally manipulated brood size in spotless starlings (Sturnus unicolor) to test the causal relationship between early stress, oxidative and corticosterone-mediated stress and telomere shortening. Our results show that experimentally enlarged brood sizes led to a reduction in morphometric development on nestlings, the effect being stronger for females than males. Additionally, basal corticosterone levels increased with increasing brood size in female nestlings. Neither plasma antioxidant status nor malondialdehyde levels (a marker of lipid peroxidation) were affected by experimental brood size, although the levels of a key intracellular antioxidant (glutathione) decreased with increasing brood size. We found that the treatment showed a quadratic effect on nestling telomere lengths: these were shortened either by increases or by decreases in the original brood size. Our study provides experimental evidence for a link between developmental stress and telomere length, but does not support a direct causal link of this reduction with corticosterone or oxidative stress. We suggest that future studies should focus on how telomere length responds to additional markers of allostatic load.}, } @article {pmid30387214, year = {2019}, author = {Rodrigues, JFM and Villalobos, F and Iverson, JB and Diniz-Filho, JAF}, title = {Climatic niche evolution in turtles is characterized by phylogenetic conservatism for both aquatic and terrestrial species.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {66-75}, doi = {10.1111/jeb.13395}, pmid = {30387214}, issn = {1420-9101}, support = {#380759/2017-9//Instituto Nacional de Ciência e Tecnologia Ecologia, Evolução e Conservação da Biodiversidade (INCT-EECBio) UFG/ ; #465610/2014-5//Instituto Nacional de Ciência e Tecnologia Ecologia, Evolução e Conservação da Biodiversidade (INCT-EECBio) UFG/ ; //Consejo Nacional de Ciencia y Tecnología/ ; //Fundação de Amparo à Pesquisa do Estado de Goiás/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Environmental Protection Agency/ ; //Joseph Moore Museum of Natural History/ ; //Earlham College/ ; DDI-9807898//National Science Foundation/ ; //Conservation International/ ; 380759/2017-9//National Institutes for Science and Technology (INCT) in Ecology/ ; 465610/2014-5//National Institutes for Science and Technology (INCT) in Ecology/ ; //CONACYT/ ; //FAPEG/ ; 465610/2014-5//MCTIC/CNPq/ ; }, abstract = {Understanding how the climatic niche of species evolved has been a topic of high interest in current theoretical and applied macroecological studies. However, little is known regarding how species traits might influence climatic niche evolution. Here, we evaluated patterns of climatic niche evolution in turtles (tortoises and freshwater turtles) and whether species habitat (terrestrial or aquatic) influences these patterns. We used phylogenetic, climatic and distribution data for 261 species to estimate their climatic niches. Then, we compared whether niche overlap between sister species was higher than between random species pairs and evaluated whether niche optima and rates varied between aquatic and terrestrial species. Sister species had higher values of niche overlap than random species pairs, suggesting phylogenetic climatic niche conservatism in turtles. The climatic niche evolution of the group followed an Ornstein-Uhlenbeck model with different optimum values for aquatic and terrestrial species, but we did not find consistent evidence of differences in their rates of climatic niche evolution. We conclude that phylogenetic climatic niche conservatism occurs among turtle species. Furthermore, terrestrial and aquatic species occupy different climatic niches but these seem to have evolved at similar evolutionary rates, reinforcing the importance of habitat in understanding species climatic niches and their evolution.}, } @article {pmid30386588, year = {2018}, author = {Young, S and Rode-Margono, J and Amin, R}, title = {Software to facilitate and streamline camera trap data management: A review.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9947-9957}, pmid = {30386588}, issn = {2045-7758}, abstract = {Improving technology and increasing affordability mean that camera trapping-the use of remotely triggered cameras to photograph wildlife-is becoming an increasingly common tool in the monitoring and conservation of wild populations. Each camera trap study generates a vast amount of data, which need to be processed and labeled before analysis. Traditionally, processing camera trap data has been performed manually by entering data into a spreadsheet. This is time-consuming, prone to human error, and data management may be inconsistent between projects, hindering collaboration. Recently, several programs have become available to facilitate and quicken data processing. Here, we review available software and assess their ability to better standardize camera trap data management and facilitate data sharing and collaboration. To identify available software for camera trap data management, we used internet searches and contacted researchers and practitioners working on large camera trap projects, as well as software developers. We tested all available programs against a range of software characteristics in addition to their ability to record a suite of important data variables extracted from images. We identified and reviewed 12 available programs for the management of camera trap data. These ranged from simple software assisting with the extraction of metadata from an image, through to comprehensive programs that facilitate data entry and analysis. Many of the programs tested were developed for use on specific studies and so do not cover all possible software or data collection requirements that different projects may have. We highlight the importance of a standardized software solution for camera trap data management. This approach would allow all possible data to be collected, enabling researchers to share data and contribute to other studies, as well as facilitating multi-project comparisons. By standardizing camera trap data collection and management in this way, future studies would be better placed to guide conservation policy on a global level.}, } @article {pmid30386587, year = {2018}, author = {Pirotta, E and Booth, CG and Costa, DP and Fleishman, E and Kraus, SD and Lusseau, D and Moretti, D and New, LF and Schick, RS and Schwarz, LK and Simmons, SE and Thomas, L and Tyack, PL and Weise, MJ and Wells, RS and Harwood, J}, title = {Understanding the population consequences of disturbance.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9934-9946}, pmid = {30386587}, issn = {2045-7758}, abstract = {Managing the nonlethal effects of disturbance on wildlife populations has been a long-term goal for decision makers, managers, and ecologists, and assessment of these effects is currently required by European Union and United States legislation. However, robust assessment of these effects is challenging. The management of human activities that have nonlethal effects on wildlife is a specific example of a fundamental ecological problem: how to understand the population-level consequences of changes in the behavior or physiology of individual animals that are caused by external stressors. In this study, we review recent applications of a conceptual framework for assessing and predicting these consequences for marine mammal populations. We explore the range of models that can be used to formalize the approach and we identify critical research gaps. We also provide a decision tree that can be used to select the most appropriate model structure given the available data. Synthesis and applications: The implementation of this framework has moved the focus of discussion of the management of nonlethal disturbances on marine mammal populations away from a rhetorical debate about defining negligible impact and toward a quantitative understanding of long-term population-level effects. Here we demonstrate the framework's general applicability to other marine and terrestrial systems and show how it can support integrated modeling of the proximate and ultimate mechanisms that regulate trait-mediated, indirect interactions in ecological communities, that is, the nonconsumptive effects of a predator or stressor on a species' behavior, physiology, or life history.}, } @article {pmid30386586, year = {2018}, author = {Hacking, JD and Stuart-Fox, D and Godfrey, SS and Gardner, MG}, title = {Specific MHC class I supertype associated with parasite infection and color morph in a wild lizard population.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9920-9933}, pmid = {30386586}, issn = {2045-7758}, abstract = {The major histocompatibility complex (MHC) is a large gene family that plays a central role in the immune system of all jawed vertebrates. Nonavian reptiles are underrepresented within the MHC literature and little is understood regarding the mechanisms maintaining MHC diversity in this vertebrate group. Here, we examined the relative roles of parasite-mediated selection and sexual selection in maintaining MHC class I diversity of a color polymorphic lizard. We discovered evidence for parasite-mediated selection acting via rare-allele advantage or fluctuating selection as ectoparasite load was significantly lower in the presence of a specific MHC supertype (functional clustering of alleles): supertype four. Based on comparisons between ectoparasite prevalence and load, and assessment of the impact of ectoparasite load on host fitness, we suggest that supertype four confers quantitative resistance to ticks or an intracellular tickborne parasite. We found no evidence for MHC-associated mating in terms of pair genetic distance, number of alleles, or specific supertypes. An association was uncovered between supertype four and male throat color morph. However, it is unlikely that male throat coloration acts as a signal of MHC genotype to conspecifics because we found no evidence to suggest that male throat coloration predicts male mating status. Overall, our results suggest that parasite-mediated selection plays a role in maintaining MHC diversity in this population via rare-allele advantage and/or fluctuating selection. Further work is required to determine whether sexual selection also plays a role in maintaining MHC diversity in agamid lizards.}, } @article {pmid30386585, year = {2018}, author = {Skarin, A and Sandström, P and Alam, M}, title = {Out of sight of wind turbines-Reindeer response to wind farms in operation.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9906-9919}, pmid = {30386585}, issn = {2045-7758}, abstract = {To meet the expanding land use required for wind energy development, a better understanding of the effects on terrestrial animals' responses to such development is required. Using GPS-data from 50 freely ranging female reindeer (Rangifer tarandus) in the Malå reindeer herding community, Sweden, we determined reindeer calving sites and estimated reindeer habitat selection using resource selection functions (RSF). RSFs were estimated at both second- (selection of home range) and third-order (selection within home range) scale in relation to environmental variables, wind farm (WF) development phase (before construction, construction, and operation), distance to the WFs and at the second-order scale whether the wind turbines were in or out of sight of the reindeer. We found that the distance between reindeer calving site and WFs increased during the operation phase, compared to before construction. At both scales of selection, we found a significant decrease in habitat selection of areas in proximity of the WFs, in the same comparison. The results also revealed a shift in home range selection away from habitats where wind turbines became visible toward habitats where the wind turbines were obscured by topography (increase in use by 79% at 5 km). We interpret the reindeer shift in home range selection as an effect of the wind turbines per se. Using topography and land cover information together with the positions of wind turbines could therefore help identify sensitive habitats for reindeer and improve the planning and placement of WFs. In addition, we found that operation phase of these WFs had a stronger adverse impact on reindeer habitat selection than the construction phase. Thus, the continuous running of the wind turbines making a sound both day and night seemed to have disturbed the reindeer more than the sudden sounds and increased human activity during construction work.}, } @article {pmid30386584, year = {2018}, author = {Schwarz, D and Spitzer, SM and Thomas, AC and Kohnert, CM and Keates, TR and Acevedo-Gutiérrez, A}, title = {Large-scale molecular diet analysis in a generalist marine mammal reveals male preference for prey of conservation concern.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9889-9905}, pmid = {30386584}, issn = {2045-7758}, abstract = {Sex-specific diet information is important in the determination of predator impacts on prey populations. Unfortunately, the diet of males and females can be difficult to describe, particularly when they are marine predators. We combined two molecular techniques to describe haul-out use and prey preferences of male and female harbor seals (Phoca vitulina) from Comox and Cowichan Bay (Canada) during 2012-2013. DNA metabarcoding quantified the diet proportions comprised of prey species in harbor seal scat, and qPCR determined the sex of the individual that deposited each scat. Using 287 female and 260 male samples, we compared the monthly sex ratio with GLMs and analyzed prey consumption relative to sex, season, site, and year with PERMANOVA. The sex ratio between monthly samples differed widely in both years (range = 12%-79% males) and showed different patterns at each haul-out site. Male and female diet differed across both years and sites: Females consumed a high proportion of demersal fish species while males consumed more salmonid species. Diet composition was related to both sex and season (PERMANOVA: R2 = 27%, p < 0.001; R2 = 24%, p < 0.001, respectively) and their interaction (PERMANOVA: R2 = 11%, p < 0.001). Diet differences between males and females were consistent across site and year, suggesting fundamental foraging differences, including that males may have a larger impact on salmonids than females. Our novel combination of techniques allowed for both prey taxonomic and spatiotemporal resolution unprecedented in marine predators.}, } @article {pmid30386583, year = {2018}, author = {Pietrzak, B and Grzesiuk, M and Dorosz, J and Mikulski, A}, title = {When males outlive females: Sex-specific effects of temperature on lifespan in a cyclic parthenogen.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9880-9888}, pmid = {30386583}, issn = {2045-7758}, abstract = {Lifespans of males and females frequently differ as a consequence of different life history strategies adopted to maximize fitness. It is well visible in cyclic parthenogens, such as water fleas of the genus Daphnia, where males appear in the population usually only for periods when receptive females are available. Moreover, even within one sex, different life history strategies and mechanisms regulating lifespan may exist. Previous studies suggested that Daphnia males may regulate their lifespan by staying in colder waters than females. We hypothesize that such behavioral mechanism should be associated with stronger reaction to low temperature-that is greater lifespan extension in males than in females. In this study, we monitored survivorship of Daphnia magna females and males of three clonal lines cultured at 16 or 20°C. The results did not provide a species-level corroboration of our hypothesis; instead, they revealed very strong intraspecific differences in the responses of male and female lifespan to temperature change. They further suggest the existence of parallel life history strategies, hypothesis whose tests would bring new insights into the ecology of males in cyclic parthenogens.}, } @article {pmid30386582, year = {2018}, author = {Coster, SS and Welsh, AB and Costanzo, G and Harding, SR and Anderson, JT and McRae, SB and Katzner, TE}, title = {Genetic analyses reveal cryptic introgression in secretive marsh bird populations.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9870-9879}, pmid = {30386582}, issn = {2045-7758}, abstract = {Hybridization is common in bird populations but can be challenging for management, especially if one of the two parent species is of greater conservation concern than the other. King rails (Rallus elegans) and clapper rails (R. crepitans) are two marsh bird species with similar morphologies, behaviors, and overlapping distributions. The two species are found along a salinity gradient with the king rail in freshwater marshes and the clapper in estuarine marshes. However, this separation is not absolute; they are occasionally sympatric, and there are reports of interbreeding. In Virginia, USA, both king and clapper rails are identified by the state as Species of Greater Conservation Need, although clappers are thought to be more abundant and king rails have a higher priority ranking. We used a mitochondrial DNA marker and 13 diagnostic nuclear single nucleotide polymorphisms (SNPs) to identify species, classify the degree of introgression, and explore the evolutionary history of introgression in two putative clapper rail focal populations along a salinity gradient in coastal Virginia. Genetic analyses revealed cryptic introgression with site-specific rates of admixture. We identified a pattern of introgression where clapper rail alleles predominate in brackish marshes. These results suggest clapper rails may be displacing king rails in Virginia coastal waterways, most likely as a result of ecological selection. As introgression can result in various outcomes from outbreeding depression to local adaptation, continued monitoring of these populations would allow further exploration of hybrid fitness and inform conservation management.}, } @article {pmid30386581, year = {2018}, author = {Vane, K and Larsen, T and Scholz-Böttcher, BM and Kopke, B and Ekau, W}, title = {Ontogenetic resource utilization and migration reconstruction with δ13C values of essential amino acids in the Cynoscion acoupa otolith.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9859-9869}, pmid = {30386581}, issn = {2045-7758}, abstract = {With the increasing anthropogenic impacts on fish habitats, it has become more important to understand which primary resources sustain fish populations. This resource utilization can differ between fish life stages, and individuals can migrate between habitats in search of resources. Such lifetime information is difficult to obtain due to the large spatial and temporal scales of fish behavior. The otolith organic matrix has the potential to indicate this resource utilization and migration with δ13C values of essential amino acids (EAAs), which are a direct indication of the primary producers. In a proof-of-concept study, we selected the Acoupa weakfish, Cynoscion acoupa, as a model fish species with distinct ontogenetic migration patterns. While it inhabits the Brazilian mangrove estuaries during juvenile stages, it moves to the coastal shelf as an adult. Thus, we expected that lifetime resource utilization and migration would be reflected in δ13CEAA patterns and baseline values in C. acoupa otoliths. By analyzing the C. acoupa otolith edges across a size range of 12-119 cm, we found that baseline δ13CEAA values increased with size, which indicated an estuarine to coastal shelf distribution. This trend is highly correlated with inorganic δ13C values. The δ13CEAA patterns showed that estuarine algae rather than mangrove-derived resources supported the juvenile C. acoupa populations. Around the juvenile size of 40 cm, resource utilization overlapped with those of adults and mean baseline δ13CEAA values increased. This trend was confirmed by comparing otolith core and edges, although with some individuals potentially migrating over longer distances than others. Hence, δ13CEAA patterns and baseline values in otoliths have great potential to reconstruct ontogenetic shifts in resource use and habitats. The insight could aid in predictions on how environmental changes affect fish populations by identifying the controlling factors at the base of the food web.}, } @article {pmid30386580, year = {2018}, author = {Whitehair, L and Fulé, PZ and Meador, AS and Azpeleta Tarancón, A and Kim, YS}, title = {Fire regime on a cultural landscape: Navajo Nation.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9848-9858}, pmid = {30386580}, issn = {2045-7758}, abstract = {Fire has played an important role in the evolutionary environment of global ecosystems, and Indigenous peoples have long managed natural resources in these fire-prone environments. We worked with the Navajo Nation Forestry Department to evaluate the historical role of fire on a 50 km2 landscape bisected by a natural mountain pass. We used fifty 5-ha circular plots to collect proxy fire history data on fire-scarred trees, stumps, logs, and snags in a coniferous forest centered on a key mountain pass. The fire history data were categorized into three groups: All (all 50 plots), Corridor (25 plots closest to Buffalo Pass drainage), and Outer (remaining 25 plots, farther from pass). We assessed spatial and temporal patterns of fire recurrence and fire-climate relationships. The landscape experienced frequent fires from 1644, the earliest fire date with sufficient sample depth, to 1920, after which fire occurrence was interrupted. The mean fire interval (MFI) for fire dates scarring 10% or more of the samples was 6.25 years; there were 13 large-scale fires identified with the 25% filter with an MFI of 22.6 years. Fire regimes varied over the landscape, with an early reduction in fire occurrence after 1829, likely associated with pastoralism, in the outer uplands away from the pass. In contrast, the pass corridor had continuing fire occurrence until the early 20th century.Synthesis. Fires were synchronized with large-scale top-down climatic oscillations (drought and La Niña), but the spatially explicit landscape sampling design allowed us to detect bottom-up factors of topography, livestock grazing, and human movement patterns that interacted in complex ways to influence the fire regime at fine scales. Since the early 20th century, however, fires have been completely excluded. Fuel accumulation in the absence of fire and warming climate present challenges for future management.}, } @article {pmid30386579, year = {2018}, author = {Cozzarolo, CS and Jenkins, T and Toews, DPL and Brelsford, A and Christe, P}, title = {Prevalence and diversity of haemosporidian parasites in the yellow-rumped warbler hybrid zone.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9834-9847}, pmid = {30386579}, issn = {2045-7758}, abstract = {Parasites can play a role in speciation, by exerting different selection pressures on different host lineages, leading to reproductive barriers in regions of possible interbreeding. Hybrid zones therefore offer an ideal system to study the effect of parasites on speciation. Here, we study a hybrid zone in the foothills of the Rocky Mountains where two yellow-rumped warbler subspecies, Setophaga coronata coronata and S. c. auduboni, interbreed. There is partial reproductive isolation between them, but no evidence of strong assortative mating within the hybrid zone, suggesting the existence of a postzygotic selection against hybrids. Here, we test whether haemosporidian parasites might play a role in selecting against hybrids between S. c. coronata and S. c. auduboni. We screened birds from five transects across the hybrid zone for three phylogenetic groupings of avian haemosporidians Plasmodium, Haemoproteus and Leucocytozoon parasites and quantified intensity of infection. Contrary to our prediction, hybrids did not have higher haemosporidian parasite prevalence. Variation in Haemoproteus prevalence was best explained by an interaction between a birds' hybrid index and elevation, while the probability of infection with Leucocytozoon parasites was only influenced by elevation. We also found no significant difference in the diversity of haemosporidian lineages between the warbler subspecies and their hybrids. Finally, intensity of infection by Haemoproteus increased significantly with elevation, but was not significantly linked to birds' hybrid index. In conclusion, our data suggest that haemosporidian parasites do not seem to play a major role in selecting against hybrids in this system.}, } @article {pmid30386578, year = {2018}, author = {Hansson, A and Olsson, M}, title = {Incubation temperature and parental identity determine sex in the Australian agamid lizard Ctenophorus pictus.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9827-9833}, pmid = {30386578}, issn = {2045-7758}, abstract = {Sex determination in Australian agamid lizards shows a complex framework of different mechanisms, varying even among closely related taxa. It is clear that discrete classification of these species as either having genetic (GSD) or environmental sex determination (ESD) does not agree with empirical data. Although many species in this group show temperature-dependent sex determination (TSD), recent evidence suggests additional genetic or epigenetic effects. A proposed model explaining the adaptive significance and evolution of TSD in short-lived agamids predicts that selection will favor temperature-biased sex ratios in species with intense male-male competition. Here, we use experimental incubation at (near) constant temperatures to test whether the sex of Australian painted dragons (Ctenophorus pictus) is influenced by temperature, building on previous research yet to have reached an agreement regarding the role of temperature in this species. In this study, incubation temperature and parental identity affected hatchling sex suggesting that environment and genetics may work in concert to determine sex in this species. Although our results are consistent with TSD, our data cannot rule out a temperature-by-sex effect on egg or hatchling mortality. However, our findings together with the observed differences of sex determination systems in closely related species within this genus may provide novel opportunities to address fundamental questions in the evolution of sex determination systems.}, } @article {pmid30386577, year = {2018}, author = {Pauli, NC and Paiva, F and Briski, E}, title = {Are Ponto-Caspian species able to cross salinity barriers? A case study of the gammarid Pontogammarus maeoticus.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9817-9826}, pmid = {30386577}, issn = {2045-7758}, abstract = {Recently, Ponto-Caspian species (i.e., area of Azov, Black, and Caspian Seas) have invaded brackish and freshwater habitats of the North and Baltic Seas and the Laurentian Great Lakes in much higher numbers than expected based on shipping frequency and environmental conditions among these regions. Therefore, it has been suggested that Ponto-Caspian species may have inherent advantages over other species in colonizing new habitats, or that they are of freshwater origin. Artificial selection offers the possibility to investigate phenotypic plasticity, shifts in environmental tolerance, and heritability of environmentally sensitive traits; therefore, in this study, we conducted artificial selection experiments on Ponto-Caspian amphipod Pontogammarus maeoticus collected from 10 PSU to evaluate adaptation capacity of this species to different salinities, and to shed additional light on a possible freshwater origin of Ponto-Caspian invaders. Our results indicated that selection to lower salinity than that of the population's ambient salinity is possible within few generations due to a likely existence of standing polymorphic variation for selection to act on. In contrast, selection to higher salinity was unsuccessful because the phenotypic variation was mainly caused by environmental variance and therefore might depend on new mutations. Consequently, the results of our study suggest that the tested species might be of freshwater origin and lacks necessary genetic background for adaptation to fully marine conditions. Further selection studies using more species and populations, as well as molecular techniques, should be conducted to elucidate if other Ponto-Caspian invaders are of freshwater origin as well.}, } @article {pmid30386576, year = {2018}, author = {Zhang, YM and Bass, AIH and Fernández, DC and Sharanowski, BJ}, title = {Habitat or temporal isolation: Unraveling herbivore-parasitoid speciation patterns using double digest RADseq.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9803-9816}, pmid = {30386576}, issn = {2045-7758}, abstract = {Ecological speciation is often observed in phytophagous insects and their parasitoids due to divergent selection caused by host-associated or temporal differences. Most previous studies have utilized limited genetic markers or distantly related species to look for reproductive barriers of speciation. In our study, we focus on closely related species of Lygus bugs and two sister species of Peristenus parasitoid wasps. Using mitochondrial DNA COI and genomewide SNPs generated using ddRADseq, we tested for potential effects of host-associated differentiation (HAD) or temporal isolation in this system. While three species of Lygus are clearly delineated with both COI and SNPs, no evidence of HAD or temporal differentiation was detected. Two Peristenus sister species were supported by both sets of markers and separated temporally, with P. mellipes emerging early in June and attacking the first generation of Lygus, while P. howardi emerging later in August and attacking the second generation of their hosts. This is one of the few studies to examine closely related hosts and parasitoids to examine drivers of diversification. Given the results of this study, the Lygus-Peristenus system demonstrates temporal isolation as a potential barrier to reproductive isolation for parasitoids, which could indicate higher parasitoid diversity in regions of multivoltine hosts. This study also demonstrates that incorporating systematics improves studies of parasitoid speciation, particularly by obtaining accurate host records through rearing, carefully delimiting cryptic species and examining population-level differences with genomic-scale data among closely related taxa.}, } @article {pmid30386575, year = {2018}, author = {Kreisinger, J and Schmiedová, L and Petrželková, A and Tomášek, O and Adámková, M and Michálková, R and Martin, JF and Albrecht, T}, title = {Fecal microbiota associated with phytohaemagglutinin-induced immune response in nestlings of a passerine bird.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9793-9802}, pmid = {30386575}, issn = {2045-7758}, abstract = {The vertebrate gastrointestinal tract is inhabited by a diverse community of bacteria, the so-called gut microbiota (GM). Research on captive mammalian models has revealed tight mutual interactions between immune functions and GM. However, our knowledge of GM versus immune system interactions in wild populations and nonmammalian species remains poor. Here, we focus on the association between GM community structure and immune response measured via the phytohaemagglutinin (PHA) skin swelling test in 12-day-old nestlings of a passerine bird, the barn swallow (Hirundo rustica). The PHA test, a widely used method in field ecoimmunology, assesses cell-mediated immunity. GM structure was inferred based on high-throughput 16S rRNA sequencing of microbial communities in fecal samples. We did not find any association between PHA response and GM diversity; however, our data revealed that the intensity of PHA response was correlated with differences in GM composition at the whole-community level. Ten bacterial operational taxonomic units corresponding to both putative commensal and pathogens were identified as drivers of the compositional variation. In conclusion, our study suggests existence of GM versus immune system interactions in a free-living nonmammalian species, which corresponds with previous research on captive vertebrates.}, } @article {pmid30386574, year = {2018}, author = {Kellner, A and Carver, S and Scorza, V and McKee, CD and Lappin, M and Crooks, KR and VandeWoude, S and Antolin, MF}, title = {Transmission pathways and spillover of an erythrocytic bacterial pathogen from domestic cats to wild felids.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9779-9792}, pmid = {30386574}, issn = {2045-7758}, abstract = {Many pathogens infect multiple hosts, and spillover from domestic to wild species poses a significant risk of spread of diseases that threaten wildlife and humans. Documentation of cross-species transmission, and unraveling the mechanisms that drive it, remains a challenge. Focusing on co-occurring domestic and wild felids, we evaluate possible transmission mechanisms and evidence of spillover of "Candidatus Mycoplasma haemominutum" (CMhm), an erythrocytic bacterial parasite of cats. We examine transmission and possibility of spillover by analyzing CMhm prevalence, modeling possible transmission pathways, deducing genotypes of CMhm pathogens infecting felid hosts based on sequences of the bacterial 16S rRNA gene, and conducting phylogenetic analyses with ancestral state reconstruction to identify likely cross-species transmission events. Model selection analyses suggest both indirect (i.e., spread via vectors) and direct (i.e., via interspecific predation) pathways may play a role in CMhm transmission. Phylogenetic analyses indicate that transmission of CMhm appears to predominate within host species, with occasional spillover, at unknown frequency, between species. These analyses are consistent with transmission by predation of smaller cats by larger species, with subsequent within-species persistence after spillover. Our results implicate domestic cats as a source of global dispersal and spillover to wild felids via predation. We contribute to the emerging documentation of predation as a common means of pathogen spillover from domestic to wild cats, including pathogens of global conservation significance. These findings suggest risks for top predators as bioaccumulators of pathogens from subordinate species.}, } @article {pmid30386573, year = {2018}, author = {Pickett, EP and Fraser, WR and Patterson-Fraser, DL and Cimino, MA and Torres, LG and Friedlaender, AS}, title = {Spatial niche partitioning may promote coexistence of Pygoscelis penguins as climate-induced sympatry occurs.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9764-9778}, pmid = {30386573}, issn = {2045-7758}, abstract = {Climate-induced range overlap can result in novel interactions between similar species and potentially lead to competitive exclusion. The West Antarctic Peninsula (WAP) is one of the most rapidly warming regions on Earth and is experiencing a poleward climate migration from a polar to subpolar environment. This has resulted in a range expansion of the ice-intolerant gentoo penguins (Pygoscelis papua) and a coincident decrease in ice-obligate Adélie penguins (P. adeliae) near Palmer Station, Anvers Island, WAP. Ecologically similar species that share a limited prey resource must occupy disparate foraging niches in order to co-exist. Therefore, we determined the extent of foraging and dietary niche segregation between Adélie and gentoo penguins during the austral breeding season near Palmer Station. This research was conducted across six breeding seasons, from 2009 to 2014, which allowed us to investigate niche overlap in the context of interannual resource variability. Using biotelemetry and diet sampling, we found substantial overlap in the diets of Adélie and gentoo penguins, who primarily consumed Antarctic krill (Euphausia superba); however, our results showed that Adélie and gentoo penguins partitioned this shared prey resource through horizontal segregation of their core foraging areas. We did not find evidence that Antarctic krill were a limiting resource during the breeding season or that climate-induced sympatry of Adélie and gentoo penguins resulted in competition for prey or caused the subsequent differing population trajectories. This apparent absence of resource competition between Adélie and gentoo penguins throughout this study implies that current population trends in this region are governed by other biological and physical factors. Our results highlight the importance of understanding the mechanistic processes that influence top predator populations in the context of climate-driven ecosystem shifts.}, } @article {pmid30386572, year = {2018}, author = {Gaitonde, N and Joshi, J and Kunte, K}, title = {Evolution of ontogenic change in color defenses of swallowtail butterflies.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9751-9763}, pmid = {30386572}, issn = {2045-7758}, abstract = {Natural selection by visually hunting predators has led to the evolution of color defense strategies such as masquerade, crypsis, and aposematism that reduce the risk of predation in prey species. These color defenses are not mutually exclusive, and switches between strategies with ontogenic development are widespread across taxa. However, the evolutionary dynamics of ontogenic color change are poorly understood. Using comparative phylogenetics, we studied the evolution of color defenses in the complex life cycles of swallowtail butterflies (family Papilionidae). We also tested the relative importance of life history traits, chemical and visual backgrounds, and ancestry on the evolution of protective coloration. We found that vulnerable early- and late-instar caterpillars of species that feed on sparsely vegetated, toxic plants were aposematic, whereas species that feed on densely vegetated, nontoxic plants had masquerading and cryptic caterpillars. Masquerading caterpillars resembled bird droppings at early instars and transitioned to crypsis with an increase in body size at late instars. The immobile pupae-safe from motion-detecting, visually hunting predators-retained the ancestral cryptic coloration in all lineages, irrespective of the toxic nature of the host plant. Thus, color defense strategy (masquerade, crypsis, or aposematism) at a particular lifestage in the life cycle of swallowtail butterflies was determined by the interaction between life history traits such as body size and motion levels, phytochemical and visual backgrounds, and ancestry. We show that ontogenic color change in swallowtail butterflies is an adaptive response to age-dependent vulnerability to predation.}, } @article {pmid30386571, year = {2018}, author = {Carroll, T and Gillingham, PK and Stafford, R and Bullock, JM and Diaz, A}, title = {Improving estimates of environmental change using multilevel regression models of Ellenberg indicator values.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9739-9750}, pmid = {30386571}, issn = {2045-7758}, abstract = {Ellenberg indicator values (EIVs) are a widely used metric in plant ecology comprising a semi-quantitative description of species' ecological requirements. Typically, point estimates of mean EIV scores are compared over space or time to infer differences in the environmental conditions structuring plant communities-particularly in resurvey studies where no historical environmental data are available. However, the use of point estimates as a basis for inference does not take into account variance among species EIVs within sampled plots and gives equal weighting to means calculated from plots with differing numbers of species. Traditional methods are also vulnerable to inaccurate estimates where only incomplete species lists are available.We present a set of multilevel (hierarchical) models-fitted with and without group-level predictors (e.g., habitat type)-to improve precision and accuracy of plot mean EIV scores and to provide more reliable inference on changing environmental conditions over spatial and temporal gradients in resurvey studies. We compare multilevel model performance to GLMMs fitted to point estimates of mean EIVs. We also test the reliability of this method to improve inferences with incomplete species lists in some or all sample plots. Hierarchical modeling led to more accurate and precise estimates of plot-level differences in mean EIV scores between time-periods, particularly for datasets with incomplete records of species occurrence. Furthermore, hierarchical models revealed directional environmental change within ecological habitat types, which less precise estimates from GLMMs of raw mean EIVs were inadequate to detect. The ability to compute separate residual variance and adjusted R2 parameters for plot mean EIVs and temporal differences in plot mean EIVs in multilevel models also allowed us to uncover a prominent role of hydrological differences as a driver of community compositional change in our case study, which traditional use of EIVs would fail to reveal. Assessing environmental change underlying ecological communities is a vital issue in the face of accelerating anthropogenic change. We have demonstrated that multilevel modeling of EIVs allows for a nuanced estimation of such from plant assemblage data changes at local scales and beyond, leading to a better understanding of temporal dynamics of ecosystems. Further, the ability of these methods to perform well with missing data should increase the total set of historical data which can be used to this end.}, } @article {pmid30386570, year = {2018}, author = {Biggins, JD and Thompson, JE and Birkhead, TR}, title = {Accurately quantifying the shape of birds' eggs.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9728-9738}, pmid = {30386570}, issn = {2045-7758}, abstract = {Describing the range of avian egg shapes quantitatively has long been recognized as difficult. A variety of approaches has been adopted, some of which aim to capture the shape accurately and some to provide intelligible indices of shape. The objectives here are to show that a (four-parameter) method proposed by Preston (1953, The Auk, 70, 160) is the best option for quantifying egg shape, to provide and document an R program for applying this method to suitable photographs of eggs, to illustrate that intelligible shape indices can be derived from the summary this method provides, to review shape indices that have been proposed, and to report on the errors introduced using photographs of eggs at rest rather than horizontal.}, } @article {pmid30386569, year = {2018}, author = {Suwal, MK and Huettmann, F and Regmi, GR and Vetaas, OR}, title = {Parapatric subspecies of Macaca assamensis show a marginal overlap in their predicted potential distribution: Some elaborations for modern conservation management.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9712-9727}, pmid = {30386569}, issn = {2045-7758}, abstract = {Phylogenetic niche conservatism implies that sister taxa will have similar niches, although the niches of disjunct subspecies may evolve differently. This study uses Macaca assamensis, subspecies assamensis and pelops, to investigate the similarities of realized climatic niches of two disjunct subspecies (separated by the Brahmaputra River) along with a similarity analysis of their respective regions' climate. Modeled distributions were used to quantify their potential distribution under current and future climate scenarios. The climatic similarity between regions of each subspecies was tested with principal component analysis (PCA), and the realized climatic niche overlap between two subspecies was tested with a multivariate analysis of variance (MANOVA) on a subset of the least correlated variables out of 24 publicly available topo-bioclimatic variables. Tukey's honest significance difference (HSD) was used to test the range differences (on all 24 variables) between subspecies. The potential distribution of both taxa in the current climate and projected future climate was model-predicted using MaxEnt and Random Forest. We found significantly different climatic ranges for 21 predictors (HSD; p < 0.05) for the two subspecies, significantly different climatic conditions for their regions (using PCA; p < 0.001), and significantly different realized climatic niches for the two subspecies (MANOVA; p < 0.001). The distribution models generated a larger potential area than the currently known distributions. Although literature show that the Brahmaputra River is an effective dispersal barrier, we found some of the neighboring geographic range for both subspecies appears to be potentially suitable for the other taxon. The projected future potential areas indicate that some parts of the currently occupied geography, mostly southern parts, may become climatically unsuitable, whereas other new geographical areas may become suitable. Most of these new potential areas will be toward the north where higher and fragmented mountains, which has conservation implications.}, } @article {pmid30386568, year = {2018}, author = {Soininen, EM and Henden, JA and Ravolainen, VT and Yoccoz, NG and Bråthen, KA and Killengreen, ST and Ims, RA}, title = {Transferability of biotic interactions: Temporal consistency of arctic plant-rodent relationships is poor.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9697-9711}, pmid = {30386568}, issn = {2045-7758}, abstract = {Variability in biotic interaction strength is an integral part of food web functioning. However, the consequences of the spatial and temporal variability of biotic interactions are poorly known, in particular for predicting species abundance and distribution. The amplitude of rodent population cycles (i.e., peak-phase abundances) has been hypothesized to be determined by vegetation properties in tundra ecosystems. We assessed the spatial and temporal predictability of food and shelter plants effects on peak-phase small rodent abundance during two consecutive rodent population peaks. Rodent abundance was related to both food and shelter biomass during the first peak, and spatial transferability was mostly good. Yet, the temporal transferability of our models to the next population peak was poorer. Plant-rodent interactions are thus temporally variable and likely more complex than simple one-directional (bottom-up) relationships or variably overruled by other biotic interactions and abiotic factors. We propose that parametrizing a more complete set of functional links within food webs across abiotic and biotic contexts would improve transferability of biotic interaction models. Such attempts are currently constrained by the lack of data with replicated estimates of key players in food webs. Enhanced collaboration between researchers whose main research interests lay in different parts of the food web could ameliorate this.}, } @article {pmid30386567, year = {2018}, author = {Nagaoka, L and Rick, T and Wolverton, S}, title = {The overkill model and its impact on environmental research.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9683-9696}, pmid = {30386567}, issn = {2045-7758}, abstract = {Research on human-environment interactions that informs ecological practices and guides conservation and restoration has become increasingly interdisciplinary over the last few decades. Fueled in part by the debate over defining a start date for the Anthropocene, historical disciplines like archeology, paleontology, geology, and history are playing an important role in understanding long-term anthropogenic impacts on the planet. Pleistocene overkill, the notion that humans overhunted megafauna near the end of the Pleistocene in the Americas, Australia, and beyond, is used as prime example of the impact that humans can have on the planet. However, the importance of the overkill model for explaining human-environment interactions and anthropogenic impacts appears to differ across disciplines. There is still considerable debate, particularly within archeology, about the extent to which people may have been the cause of these extinctions. To evaluate how different disciplines interpret and use the overkill model, we conducted a citation analysis of selected works of the main proponent of the overkill model, Paul Martin. We examined the ideas and arguments for which Martin's overkill publications were cited and how they differed between archeologists and ecologists. Archeologists cite overkill as one in a combination of causal mechanisms for the extinctions. In contrast, ecologists are more likely to accept that humans caused the extinctions. Aspects of the overkill argument are also treated as established ecological processes. For some ecologists, overkill provides an analog for modern-day human impacts and supports the argument that humans have "always" been somewhat selfish overconsumers. The Pleistocene rewilding and de-extinction movements are built upon these perspectives. The use of overkill in ecological publications suggests that despite increasing interdisciplinarity, communication with disciplines outside of ecology is not always reciprocal or even.}, } @article {pmid30386566, year = {2018}, author = {Heer, K and Ullrich, KK and Hiss, M and Liepelt, S and Schulze Brüning, R and Zhou, J and Opgenoorth, L and Rensing, SA}, title = {Detection of somatic epigenetic variation in Norway spruce via targeted bisulfite sequencing.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9672-9682}, pmid = {30386566}, issn = {2045-7758}, abstract = {Epigenetic mechanisms represent a possible mechanism for achieving a rapid response of long-lived trees to changing environmental conditions. However, our knowledge on plant epigenetics is largely limited to a few model species. With increasing availability of genomic resources for many tree species, it is now possible to adopt approaches from model species that permit to obtain single-base pair resolution data on methylation at a reasonable cost. Here, we used targeted bisulfite sequencing (TBS) to study methylation patterns in the conifer species Norway spruce (Picea abies). To circumvent the challenge of disentangling epigenetic and genetic differences, we focused on four clone pairs, where clone members were growing in different climatic conditions for 24 years. We targeted >26.000 genes using TBS and determined the performance and reproducibility of this approach. We characterized gene body methylation and compared methylation patterns between environments. We found highly comparable capture efficiency and coverage across libraries. Methylation levels were relatively constant across gene bodies, with 21.3 ± 0.3%, 11.0 ± 0.4% and 1.3 ± 0.2% in the CG, CHG, and CHH context, respectively. The variance in methylation profiles did not reveal consistent changes between environments, yet we could identify 334 differentially methylated positions (DMPs) between environments. This supports that changes in methylation patterns are a possible pathway for a plant to respond to environmental change. After this successful application of TBS in Norway spruce, we are confident that this approach can contribute to broaden our knowledge of methylation patterns in natural tree populations.}, } @article {pmid30386565, year = {2018}, author = {Solano, E and Hardersen, S and Audisio, P and Amorosi, V and Senczuk, G and Antonini, G}, title = {Asymmetric hybridization in Cordulegaster (Odonata: Cordulegastridae): Secondary postglacial contact and the possible role of mechanical constraints.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9657-9671}, pmid = {30386565}, issn = {2045-7758}, abstract = {Two Cordulegaster dragonflies present in Italy, the Palaearctic and northern distributed Cordulegaster boltonii and the endemic to the south of the peninsula Cordulegaster trinacriae, meet in central Italy and give rise to individuals of intermediate morphology. By means of mitochondrial and nuclear markers and of Geometric Morphometrics applied to sexual appendages, we defined i) the geographical boundaries between the two species in Italy and ii) we determined the presence, the extent, and the genetic characteristics of the hybridization. Genetic data evidenced asymmetric hybridization with the males of C. trinacriae able to mate both interspecifically and intraspecifically. The results contrast with expectations under neutral gene introgression and sexual selection. This data, along with the morphological evidence of significant differences in size and shape of sexual appendages between the males of the two species, seem indicative of the role of mechanical constraints in intraspecific matings. The origin of the two species is dated about to 1.32 Mya and the hybridization resulted related to range expansion of the two species after Last Glacial Maximum and this led to the secondary contact between the two taxa in central Italy. At last, our results indicate that the range of C. trinacriae, a threatened and protected species, has been moving northward probably driven by climate changes. As a result, the latter species is currently intruding into the range of C. boltonii. The hybrid area is quite extended and the hybrids seem well adapted to the environment. From a conservation point of view, even if C. trinacriae has a strong genetic identity, the discovery of hybridization between the two species should be considered in a future species management.}, } @article {pmid30386564, year = {2018}, author = {Piculell, BJ and Eckhardt, LG and Hoeksema, JD}, title = {Genetically determined fungal pathogen tolerance and soil variation influence ectomycorrhizal traits of loblolly pine.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9646-9656}, pmid = {30386564}, issn = {2045-7758}, abstract = {Selection on genetically correlated traits within species can create indirect effects on one trait by selection on another. The consequences of these trait correlations are of interest because they may influence how suites of traits within species evolve under differing selection pressures, both natural and artificial. By utilizing genetic families of loblolly pine either tolerant (t) or susceptible (s) to two different suites of pathogenic fungi responsible for causing either pine decline or fusiform rust disease, we investigated trait variation and trait correlations within loblolly pine (Pinus taeda L.) by determining how ectomycorrhizal (EM) colonization relates to pathogen susceptibility. We detected interactions between susceptibility to pathogenic fungi and soil inoculation source on loblolly pine compatibility with the EM fungi Thelephora, and on relative growth rate of loblolly pine. Additionally, we detected spatial variation in the loblolly pine-EM fungi interaction, and found that variation in colonization rates by some members of the EM community is not dictated by genetic variation in the host plant but rather soil inoculation source alone. The work presented here illustrates the potential for indirect selection on compatibility with symbiotic EM fungi as a result of selection for resistance to fungal pathogens. Additionally, we present evidence that the host plant does not have a single "mycorrhizal trait" governing interactions with all EM fungi, but rather that it can interact with different fungal taxa independently. Synthesis. An understanding of the genetic architecture of essential traits in focal species is crucial if we are to anticipate and manage the results of natural and artificial selection. As demonstrated here, an essential but often overlooked symbiosis (that between plants and mycorrhizal fungi) may be indirectly influenced by directed selection on the host plant.}, } @article {pmid30386563, year = {2018}, author = {Plumb, JM}, title = {A bioenergetics evaluation of temperature-dependent selection for the spawning phenology by Snake River fall Chinook salmon.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9633-9645}, pmid = {30386563}, issn = {2045-7758}, abstract = {High water temperatures can increase the energetic cost for salmon to migrate and spawn, which can be important for Snake River fall-run Chinook salmon because they migrate great distances (>500 km) at a time when river temperatures (18-24°C) can be above their optimum temperatures (16.5°C). Average river temperatures and random combinations of migration and spawning dates were used to simulate fish travel times and determine the energetic consequences of different thermal experiences during migration. An energy threshold criterion (4 kJ/g) was also imposed on survival and spawning success, which was used to determine how prevailing temperatures might select against certain migration dates and thermal experiences, and in turn, explain the selection for the current spawning phenology of the population. Scenarios of tributary use for thermal refugia under increasing water temperatures (1, 2, and 3°C) were also run to determine which combinations of migration dates, travel rates, and resulting thermal experiences might be most affected by energy exhaustion. As expected, when compared to observations, the model under existing conditions and energy use could explain the onset, but not the end of the observed spawning migration. Simulations of early migrants had greater energy loss than late migrants regardless of the river temperature scenario, but higher temperatures disproportionately selected against a larger fraction of early-migrating fish, although using cold-water tributaries during migration provided a buffer against higher energy use at higher temperatures. The fraction of simulated fish that exceeded the threshold for migration success increased from 58% to 72% as average seasonal river temperatures over baseline temperatures increased. The model supports the conclusion that increases in average seasonal river temperatures as little as 1°C could impose greater thermal constraints on the fish, select against early migrants, and in turn, truncate the onset of the current spawning migration.}, } @article {pmid30386562, year = {2018}, author = {Donovan, VM and Burnett, JL and Bielski, CH and Birgé, HE and Bevans, R and Twidwell, D and Allen, CR}, title = {Social-ecological landscape patterns predict woody encroachment from native tree plantings in a temperate grassland.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9624-9632}, pmid = {30386562}, issn = {2045-7758}, abstract = {Afforestation is often viewed as the purposeful planting of trees in historically nonforested grasslands, but an unintended consequence is woody encroachment, which should be considered part of the afforestation process. In North America's temperate grassland biome, Eastern redcedar (Juniperus virginiana L.) is a native species used in tree plantings that aggressively invades in the absence of controlling processes. Cedar is a well-studied woody encroacher, but little is known about the degree to which cedar windbreaks, which are advocated for in agroforestry programs, are contributing to woody encroachment, what factors are associated with cedar spread from windbreaks, nor where encroachment from windbreaks is occurring in contemporary social-ecological landscapes. We used remotely sensed imagery to identify the presence and pattern of woody encroachment from windbreaks in the Nebraska Sandhills. We used multimodel inference to compare three classes of models representing three hypotheses about factors that could influence cedar spread: (a) windbreak models based on windbreak structure and design elements; (b) abiotic models focused on local environmental conditions; and (c) landscape models characterizing coupled human-natural features within the broader matrix. Woody encroachment was evident for 23% of sampled windbreaks in the Nebraska Sandhills. Of our candidate models, our inclusive landscape model carried 92% of the model weight. This model indicated that encroachment from windbreaks was more likely near roadways and less likely near farmsteads, other cedar plantings, and waterbodies, highlighting strong social ties to the distribution of woody encroachment from tree plantings across contemporary landscapes. Our model findings indicate where additional investments into cedar control can be prioritized to prevent cedar spread from windbreaks. This approach can serve as a model in other temperate regions to identify where woody encroachment resulting from temperate agroforestry programs is emerging.}, } @article {pmid30386561, year = {2018}, author = {Barichievy, C and Angeler, DG and Eason, T and Garmestani, AS and Nash, KL and Stow, CA and Sundstrom, S and Allen, CR}, title = {A method to detect discontinuities in census data.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9614-9623}, pmid = {30386561}, issn = {2045-7758}, abstract = {The distribution of pattern across scales has predictive power in the analysis of complex systems. Discontinuity approaches remain a fruitful avenue of research in the quest for quantitative measures of resilience because discontinuity analysis provides an objective means of identifying scales in complex systems and facilitates delineation of hierarchical patterns in processes, structure, and resources. However, current discontinuity methods have been considered too subjective, too complicated and opaque, or have become computationally obsolete; given the ubiquity of discontinuities in ecological and other complex systems, a simple and transparent method for detection is needed. In this study, we present a method to detect discontinuities in census data based on resampling of a neutral model and provide the R code used to run the analyses. This method has the potential for advancing basic and applied ecological research.}, } @article {pmid30386560, year = {2018}, author = {Ayllón, D and Railsback, SF and Almodóvar, A and Nicola, GG and Vincenzi, S and Elvira, B and Grimm, V}, title = {Eco-evolutionary responses to recreational fishing under different harvest regulations.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9600-9613}, pmid = {30386560}, issn = {2045-7758}, abstract = {Harvesting alters demography and life histories of exploited populations, and there is mounting evidence that rapid phenotypic changes at the individual level can occur when harvest is intensive. Therefore, recreational fishing is expected to induce both ecological and rapid evolutionary changes in fish populations and consequently requires rigorous management. However, little is known about the coupled demographic and evolutionary consequences of alternative harvest regulations in managed freshwater fisheries. We used a structurally realistic individual-based model and implemented an eco-genetic approach that accounts for microevolution, phenotypic plasticity, adaptive behavior, density-dependent processes, and cryptic mortality sources (illegal harvest and hooking mortality after catch and release). We explored the consequences of a range of harvest regulations, involving different combinations of exploitation intensity and minimum and maximum-length limits, on the eco-evolutionary trajectories of a freshwater fish stock. Our 100-year simulations of size-selective harvest through recreational fishing produced negative demographic and structural changes in the simulated population, but also plastic and evolutionary responses that compensated for such changes and prevented population collapse even under intense fishing pressure and liberal harvest regulations. Fishing-induced demographic and evolutionary changes were driven by the harvest regime, and the strength of responses increased with increasing exploitation intensity and decreasing restriction in length limits. Cryptic mortality strongly amplified the impacts of harvest and might be exerting a selective pressure that opposes that of size-selective harvest. "Slot" limits on harvestable length had overall positive effects but lower than expected ability to buffer harvest impacts. Harvest regulations strongly shape the eco-evolutionary dynamics of exploited fish stocks and thus should be considered in setting management policies. Our findings suggest that plastic and evolutionary responses buffer the demographic impacts of fishing, but intense fishing pressure and liberal harvest regulations may lead to an unstructured, juvenescent population that would put the sustainability of the stock at risk. Our study also indicates that high rates of cryptic mortality may make harvest regulations based on harvest slot limits ineffective.}, } @article {pmid30386559, year = {2018}, author = {Yoshitake, Y and Inomata, N and Sano, M and Kato, Y and Itoh, M}, title = {The P element invaded rapidly and caused hybrid dysgenesis in natural populations of Drosophila simulans in Japan.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9590-9599}, pmid = {30386559}, issn = {2045-7758}, abstract = {Transposable elements not only can change genomic positions and disperse across the gene pool, but also can jump to another species through horizontal transmission. Of late, the P element, a DNA transposon in insects, was shown to cross the genetic boundary from Drosophila melanogaster to D. simulans in Europe around 2006. To understand the dynamics of transposable elements, especially in the early stages of invasion, we examined 63 lines of D. simulans from 11 natural populations in Japan established in 1976-2015. Based on PCR analyses, P elements were demonstrated to exist in Japan in 2008 and later. One copy of the full-length P element was identified and mapped to a site on chromosome 3 L in a genome. All of 18 copies of P elements examined shared "A" at the nucleotide position 2040, which is representative of the direct descendants of the original P element that invaded in D. simulans. We also found that some lines having P elements can induce intensive gonadal dysgenesis in D. simulans at 29°C. Our present results imply that P elements in D. simulans arrived at the east end of Asia just a few years later than or almost simultaneously to the initial invasion in Europe, Africa, and North America, suggesting a more astonishingly rapid spread than previously assumed.}, } @article {pmid30386558, year = {2018}, author = {Buettel, JC and Brook, BW and Cole, A and Dickey, J and Flies, EJ}, title = {Astro-ecology? Shifting the interdisciplinary collaboration paradigm.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9586-9589}, pmid = {30386558}, issn = {2045-7758}, abstract = {We present a case study whereby ecological research on fallen trees in forest plots was advanced by a collaboration with astronomers working on the vector fields of stars and gas, and we propose a framework by which such novel collaborations can progress.}, } @article {pmid30386557, year = {2018}, author = {Paine, CET and Fox, CW}, title = {The effectiveness of journals as arbiters of scientific impact.}, journal = {Ecology and evolution}, volume = {8}, number = {19}, pages = {9566-9585}, pmid = {30386557}, issn = {2045-7758}, abstract = {Academic publishers purport to be arbiters of knowledge, aiming to publish studies that advance the frontiers of their research domain. Yet the effectiveness of journal editors at identifying novel and important research is generally unknown, in part because of the confidential nature of the editorial and peer review process. Using questionnaires, we evaluated the degree to which journals are effective arbiters of scientific impact on the domain of Ecology, quantified by three key criteria. First, journals discriminated against low-impact manuscripts: The probability of rejection increased as the number of citations gained by the published paper decreased. Second, journals were more likely to publish high-impact manuscripts (those that obtained citations in 90th percentile for their journal) than run-of-the-mill manuscripts; editors were only 23% and 41% as likely to reject an eventual high-impact paper (pre- versus postreview rejection) compared to a run-of-the-mill paper. Third, editors did occasionally reject papers that went on to be highly cited. Error rates were low, however: Only 3.8% of rejected papers gained more citations than the median article in the journal that rejected them, and only 9.2% of rejected manuscripts went on to be high-impact papers in the (generally lower impact factor) publishing journal. The effectiveness of scientific arbitration increased with journal prominence, although some highly prominent journals were no more effective than much less prominent ones. We conclude that the academic publishing system, founded on peer review, appropriately recognizes the significance of research contained in manuscripts, as measured by the number of citations that manuscripts obtain after publication, even though some errors are made. We therefore recommend that authors reduce publication delays by choosing journals appropriate to the significance of their research.}, } @article {pmid30386456, year = {2018}, author = {Xia, X and Li, J and Zhou, Z and Wang, D and Huang, J and Wang, G}, title = {High-quality-draft genome sequence of the multiple heavy metal resistant bacterium Pseudaminobacter manganicus JH-7T.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {29}, pmid = {30386456}, issn = {1944-3277}, abstract = {Pseudaminobacter manganicus JH-7T (= KCTC 52258T = CCTCC AB 2016107T) is a Gram-staining-negative, aerobic and non-motile strain that was isolated from a manganese mine. The strain JH-7T shows multiple heavy metal resistance and can effectively remove Mn2+ and Cd2+. In addition, it is able to produce exopolysaccharides (EPS), which may contribute to metal remove/adsorption. Thus, strain JH-7T shows a great potential in bioremediation of heavy metal-contaminated environment. In this study, we report the draft genomic sequence of P. manganicus JH-7T and compare it to related genomes. Strain JH-7T has a 4,842,937 bp genome size with a G + C content of 61.2%, containing 4504 protein-coding genes and 71 RNA genes. A large number of putative genes associated with heavy metal resistance and EPS synthesis are found in the genome.}, } @article {pmid30385890, year = {2018}, author = {Lidgard, S and Love, AC}, title = {Rethinking Living Fossils.}, journal = {Bioscience}, volume = {68}, number = {10}, pages = {760-770}, pmid = {30385890}, issn = {0006-3568}, abstract = {Biologists would be mistaken if they relegated living fossils to paleontological inquiry or assumed that the concept is dead. It is now used to describe entities ranging from viruses to higher taxa, despite recent warnings of misleading inferences. Current work on character evolution illustrates how analyzing living fossils and stasis in terms of parts (characters) and wholes (e.g., organisms and lineages) advances our understanding of prolonged stasis at many hierarchical levels. Instead of viewing the concept's task as categorizing living fossils, we show how its primary role is to mark out what is in need of explanation, accounting for the persistence of both molecular and morphological traits. Rethinking different conceptions of living fossils as specific hypotheses reveals novel avenues for research that integrate phylogenetics, ecological and evolutionary modeling, and evo-devo to produce a more unified theoretical outlook.}, } @article {pmid30385636, year = {2018}, author = {Lycus, P and Soriano-Laguna, MJ and Kjos, M and Richardson, DJ and Gates, AJ and Milligan, DA and Frostegård, Å and Bergaust, L and Bakken, LR}, title = {A bet-hedging strategy for denitrifying bacteria curtails their release of N2O.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11820-11825}, pmid = {30385636}, issn = {1091-6490}, mesh = {Bacteria/metabolism ; Denitrification/*physiology ; Hypoxia/metabolism ; Nitrates/*metabolism ; Nitrous Oxide/metabolism ; Oxidoreductases/metabolism ; Oxygen/metabolism ; Paracoccus denitrificans/*metabolism ; }, abstract = {When oxygen becomes limiting, denitrifying bacteria must prepare for anaerobic respiration by synthesizing the reductases NAR (NO3- → NO2-), NIR (NO2- → NO), NOR (2NO → N2O), and NOS (N2O → N2), either en bloc or sequentially, to avoid entrapment in anoxia without energy. Minimizing the metabolic burden of this precaution is a plausible fitness trait, and we show that the model denitrifier Paracoccus denitrificans achieves this by synthesizing NOS in all cells, while only a minority synthesize NIR. Phenotypic diversification with regards to NIR is ascribed to stochastic initiation of gene transcription, which becomes autocatalytic via NO production. Observed gas kinetics suggest that such bet hedging is widespread among denitrifying bacteria. Moreover, in response to oxygenation, P. denitrificans preserves NIR in the poles of nongrowing persister cells, ready to switch to anaerobic respiration in response to sudden anoxia. Our findings add dimensions to the regulatory biology of denitrification and identify regulatory traits that decrease N2O emissions.}, } @article {pmid30385635, year = {2018}, author = {Jee, AY and Cho, YK and Granick, S and Tlusty, T}, title = {Catalytic enzymes are active matter.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10812-E10821}, pmid = {30385635}, issn = {1091-6490}, mesh = {*Biocatalysis ; Catalysis ; Chemotaxis/physiology ; Diffusion ; Enzymes/*metabolism ; Hydrodynamics ; Kinetics ; }, abstract = {Using a microscopic theory to analyze experiments, we demonstrate that enzymes are active matter. Superresolution fluorescence measurements-performed across four orders of magnitude of substrate concentration, with emphasis on the biologically relevant regime around or below the Michaelis-Menten constant-show that catalysis boosts the motion of enzymes to be superdiffusive for a few microseconds, enhancing their effective diffusivity over longer timescales. Occurring at the catalytic turnover rate, these fast ballistic leaps maintain direction over a duration limited by rotational diffusion, driving enzymes to execute wormlike trajectories by piconewton forces performing work of a few kB T against viscosity. The boosts are more frequent at high substrate concentrations, biasing the trajectories toward substrate-poor regions, thus exhibiting antichemotaxis, demonstrated here experimentally over a wide range of aqueous concentrations. Alternative noncatalytic, passive mechanisms that predict chemotaxis, cross-diffusion, and phoresis, are critically analyzed. We examine the physical interpretation of our findings, speculate on the underlying mechanism, and discuss the avenues they open with biological and technological implications. These findings violate the classical paradigm that chemical reaction and motility are distinct processes, and suggest reaction-motion coupling as a general principle of catalysis.}, } @article {pmid30385634, year = {2018}, author = {Loell, K and Nanda, V}, title = {Marginal protein stability drives subcellular proteome isoelectric point.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11778-11783}, pmid = {30385634}, issn = {1091-6490}, support = {80NSSC18K0093/ImNASA/Intramural NASA/United States ; DP2 OD006478/OD/NIH HHS/United States ; }, mesh = {Computer Simulation ; Databases, Protein ; Evolution, Molecular ; Humans ; Hydrogen-Ion Concentration ; Isoelectric Point ; Lysosomes/metabolism ; Protein Folding ; Protein Stability ; Proteome/*chemistry/metabolism ; Proteomics/*methods ; Subcellular Fractions/chemistry/metabolism ; }, abstract = {There exists a positive correlation between the pH of subcellular compartments and the median isoelectric point (pI) for the associated proteomes. Proteins in the human lysosome-a highly acidic compartment in the cell-have a median pI of ∼6.5, whereas proteins in the more basic mitochondria have a median pI of ∼8.0. Proposed mechanisms reflect potential adaptations to pH. For example, enzyme active site general acid/base residue pKs are likely evolved to match environmental pH. However, such effects would be limited to a few residues on specific proteins, and might not affect the proteome at large. A protein model that considers residue burial upon folding recapitulates the correlation between proteome pI and environmental pH. This correlation can be fully described by a neutral evolution process; no functional selection is included in the model. Proteins in acidic environments incur a lower energetic penalty for burying acidic residues than basic residues, resulting in a net accumulation of acidic residues in the protein core. The inverse is true under alkaline conditions. The pI distributions of subcellular proteomes are likely not a direct result of functional adaptations to pH, but a molecular spandrel stemming from marginal stability.}, } @article {pmid30385633, year = {2018}, author = {Krepel, D and Cheng, RR and Di Pierro, M and Onuchic, JN}, title = {Deciphering the structure of the condensin protein complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11911-11916}, pmid = {30385633}, issn = {1091-6490}, mesh = {Adenosine Triphosphatases/metabolism/*physiology/*ultrastructure ; Amino Acid Sequence ; Bacterial Proteins/metabolism/physiology ; Cell Cycle Proteins/metabolism/physiology ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosome Segregation/physiology ; Chromosomes/metabolism ; DNA-Binding Proteins/metabolism/*physiology/*ultrastructure ; Databases, Protein ; Multiprotein Complexes/metabolism/*physiology/*ultrastructure ; Nuclear Proteins/metabolism ; Protein Domains ; Structure-Activity Relationship ; }, abstract = {Protein assemblies consisting of structural maintenance of chromosomes (SMC) and kleisin subunits are essential for the process of chromosome segregation across all domains of life. Prokaryotic condensin belonging to this class of protein complexes is composed of a homodimer of SMC that associates with a kleisin protein subunit called ScpA. While limited structural data exist for the proteins that comprise the (SMC)-kleisin complex, the complete structure of the entire complex remains unknown. Using an integrative approach combining both crystallographic data and coevolutionary information, we predict an atomic-scale structure of the whole condensin complex, which our results indicate being composed of a single ring. Coupling coevolutionary information with molecular-dynamics simulations, we study the interaction surfaces between the subunits and examine the plausibility of alternative stoichiometries of the complex. Our analysis also reveals several additional configurational states of the condensin hinge domain and the SMC-kleisin interaction domains, which are likely involved with the functional opening and closing of the condensin ring. This study provides the foundation for future investigations of the structure-function relationship of the various SMC-kleisin protein complexes at atomic resolution.}, } @article {pmid30385632, year = {2018}, author = {Kim, H and Yoo, S and Zhou, R and Xu, A and Bernitz, JM and Yuan, Y and Gomes, AM and Daniel, MG and Su, J and Demicco, EG and Zhu, J and Moore, KA and Lee, DF and Lemischka, IR and Schaniel, C}, title = {Oncogenic role of SFRP2 in p53-mutant osteosarcoma development via autocrine and paracrine mechanism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11128-E11137}, pmid = {30385632}, issn = {1091-6490}, support = {F99 CA212489/CA/NCI NIH HHS/United States ; R00 CA181496/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bone Neoplasms/*genetics/pathology ; Carcinogenesis/*genetics ; Cell Line, Tumor ; Cysteine-Rich Protein 61/antagonists & inhibitors/genetics ; Forkhead Box Protein M1/antagonists & inhibitors/genetics ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Li-Fraumeni Syndrome/genetics/*pathology ; Male ; Membrane Proteins/antagonists & inhibitors/*genetics ; Mice ; Mice, Nude ; Neovascularization, Pathologic/genetics ; Osteoblasts/cytology ; Osteosarcoma/*genetics/pathology ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {Osteosarcoma (OS), the most common primary bone tumor, is highly metastatic with high chemotherapeutic resistance and poor survival rates. Using induced pluripotent stem cells (iPSCs) generated from Li-Fraumeni syndrome (LFS) patients, we investigate an oncogenic role of secreted frizzled-related protein 2 (SFRP2) in p53 mutation-associated OS development. Interestingly, we find that high SFRP2 expression in OS patient samples correlates with poor survival. Systems-level analyses identified that expression of SFRP2 increases during LFS OS development and can induce angiogenesis. Ectopic SFRP2 overexpression in normal osteoblast precursors is sufficient to suppress normal osteoblast differentiation and to promote OS phenotypes through induction of oncogenic molecules such as FOXM1 and CYR61 in a β-catenin-independent manner. Conversely, inhibition of SFRP2, FOXM1, or CYR61 represses the tumorigenic potential. In summary, these findings demonstrate the oncogenic role of SFRP2 in the development of p53 mutation-associated OS and that inhibition of SFRP2 is a potential therapeutic strategy.}, } @article {pmid30385631, year = {2018}, author = {Banerjee, NS and Moore, DW and Broker, TR and Chow, LT}, title = {Vorinostat, a pan-HDAC inhibitor, abrogates productive HPV-18 DNA amplification.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11138-E11147}, pmid = {30385631}, issn = {1091-6490}, mesh = {Apoptosis/drug effects ; Bcl-2-Like Protein 11/metabolism ; Cells, Cultured ; DNA Repair/drug effects ; DNA Replication/*drug effects ; DNA, Viral/genetics ; DNA-Binding Proteins/*metabolism ; Histone Deacetylase Inhibitors/*pharmacology ; Histones/metabolism ; Human papillomavirus 18/drug effects/*genetics ; Humans ; Hydroxamic Acids/pharmacology ; Keratinocytes/virology ; Mucous Membrane/virology ; Oncogene Proteins, Viral/*metabolism ; Panobinostat/pharmacology ; Papillomavirus Infections/*drug therapy/prevention & control/transmission ; Sulfonamides/pharmacology ; Tumor Suppressor Protein p53/metabolism ; Vorinostat/*pharmacology ; }, abstract = {Human papillomaviruses (HPVs) cause epithelial proliferative diseases. Persistent infection of the mucosal epithelia by the high-risk genotypes can progress to high-grade dysplasia and cancers. Viral transcription and protein activities are intimately linked to regulation by histone acetyltransferases and histone deacetylases (HDACs) that remodel chromatin and regulate gene expression. HDACs are also essential to remodel and repair replicating chromatin to enable the progression of replication forks. As such, Vorinostat (suberoylanilide hydroximic acid), and other pan-HDAC inhibitors, are used to treat lymphomas. Here, we investigated the effects of Vorinostat on productive infection of the high-risk HPV-18 in organotypic cultures of primary human keratinocytes. HPV DNA amplifies in the postmitotic, differentiated cells of squamous epithelia, in which the viral oncoproteins E7 and E6 establish a permissive milieu by destabilizing major tumor suppressors, the pRB family proteins and p53, respectively. We showed that Vorinostat significantly reduced these E6 and E7 activities, abrogated viral DNA amplification, and inhibited host DNA replication. The E7-induced DNA damage response, which is critical for both events, was also compromised. Consequently, Vorinostat exposure led to DNA damage and triggered apoptosis in HPV-infected, differentiated cells, whereas uninfected tissues were spared. Apoptosis was attributed to highly elevated proapoptotic Bim isoforms that are known to be repressed by EZH2 in a repressor complex containing HDACs. Two other HDAC inhibitors, Belinostat and Panobinostat, also inhibited viral DNA amplification and cause apoptosis. We suggest that HDAC inhibitors are promising therapeutic agents to treat benign HPV infections, abrogate progeny virus production, and hence interrupt transmission.}, } @article {pmid30385630, year = {2018}, author = {Lang, Z and Gong, Z}, title = {A role of OsROS1 in aleurone development and nutrient improvement in rice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11659-11660}, pmid = {30385630}, issn = {1091-6490}, mesh = {DNA ; Mutation ; *Nutrients ; *Oryza ; Plant Proteins ; }, } @article {pmid30385629, year = {2018}, author = {Boers, N and Ghil, M and Rousseau, DD}, title = {Ocean circulation, ice shelf, and sea ice interactions explain Dansgaard-Oeschger cycles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11005-E11014}, pmid = {30385629}, issn = {1091-6490}, abstract = {The last glacial interval experienced abrupt climatic changes called Dansgaard-Oeschger (DO) events. These events manifest themselves as rapid increases followed by slow decreases of oxygen isotope ratios in Greenland ice core records. Despite promising advances, a comprehensive theory of the DO cycles, with their repeated ups and downs of isotope ratios, is still lacking. Here, based on earlier hypotheses, we introduce a dynamical model that explains the DO variability by rapid retreat and slow regrowth of thick ice shelves and thin sea ice in conjunction with changing subsurface water temperatures due to insulation by the ice cover. Our model successfully reproduces observed features of the records, such as the sawtooth shape of the DO cycles, waiting times between DO events across the last glacial, and the shifted antiphase relationship between Greenland and Antarctic ice cores. Our results show that these features can be obtained via internal feedbacks alone. Warming subsurface waters could have also contributed to the triggering of Heinrich events. Our model thus offers a unified framework for explaining major features of multimillennial climate variability during glacial intervals.}, } @article {pmid30385607, year = {2018}, author = {Disney, MD and Dwyer, BG and Childs-Disney, JL}, title = {Drugging the RNA World.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a034769}, pmid = {30385607}, issn = {1943-0264}, support = {DP1 NS096898/NS/NINDS NIH HHS/United States ; P01 NS099114/NS/NINDS NIH HHS/United States ; R01 GM097455/GM/NIGMS NIH HHS/United States ; }, abstract = {SUMMARYAlthough we live in the remnants of an RNA world, the world of drug discovery and chemical probes is firmly protein-centric. Developing highly selective small molecules targeting RNA is often considered to be an insurmountable challenge. Our goal is to demystify the design of such compounds. In this review, we describe various approaches to design small molecules that target RNA from sequence and the application of these compounds in RNA biology, with a focus on inhibition of human RNA-protein complexes. We have developed a library-versus-library screening approach to define selective RNA-small-molecule binding partners and applied them to disease-causing RNAs, in particular noncoding oncogenic RNAs and expanded RNA repeats, to modulate their biology in cells and animals. We also describe the design of new types of small-molecule probes that could broadly decipher the mysteries of RNA in cells.}, } @article {pmid30385606, year = {2018}, author = {Zemmel, RW}, title = {A Career for Life Scientists in Management Consulting.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a032946}, pmid = {30385606}, issn = {1943-0264}, abstract = {Compared with life sciences, management consulting is a relatively new field. Nonetheless, leading firms have assumed a central role in the global business economy and command increasing influence as advisors to corporations and organizations in the public and social sectors. Offering robust analysis, independent and expert perspectives, and-in the best cases-valuable creative input, these companies focus on helping clients to improve their performance or more effectively execute their mission.Because the top firms tackle the most complex problems for the most successful organizations in the world, they attract top graduates. But the field is no longer the sole province of those with MBAs. In recent years, the profession has increasingly diversified and now actively recruits candidates with advanced degrees in a range of disciplines-including the life sciences.Those who join the field will find many parallels between the consulting approach and scientific inquiry. As a result, life scientists have many of the intrinsic skills needed to thrive in the industry, which can offer an extraordinary breadth of assignments, global experience, and an accelerated way to learn. At leading firms, the intensive training and development offered can pave the way for partnership, in which consultants counsel senior executives as peers. Many of those who leave become entrepreneurs or join top organizations-sometimes their former clients-at a leadership level.}, } @article {pmid30385605, year = {2018}, author = {Morisaki, T and Stasevich, TJ}, title = {Quantifying Single mRNA Translation Kinetics in Living Cells.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a032078}, pmid = {30385605}, issn = {1943-0264}, abstract = {SUMMARYOne of the last hurdles to quantifying the full central dogma of molecular biology in living cells with single-molecule resolution has been the imaging of single messenger RNA (mRNA) translation. Here we describe how recent advances in protein tagging and imaging technologies are being used to precisely visualize and quantify the synthesis of nascent polypeptide chains from single mRNA in living cells. We focus on recent applications of repeat-epitope tags and describe how they enable quantification of single mRNA ribosomal densities, translation initiation and elongation rates, and translation site mobility and higher-order structure. Together with complementary live-cell assays to monitor translation using fast-maturing fluorophores and mRNA-binding protein knockoff, single-molecule studies are beginning to uncover striking and unexpected heterogeneity in gene expression at the level of translation.}, } @article {pmid30385581, year = {2018}, author = {Larson, RC}, title = {What are you waiting for?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {610}, doi = {10.1126/science.362.6414.610}, pmid = {30385581}, issn = {1095-9203}, } @article {pmid30385580, year = {2018}, author = {Laursen, NS and Friesen, RHE and Zhu, X and Jongeneelen, M and Blokland, S and Vermond, J and van Eijgen, A and Tang, C and van Diepen, H and Obmolova, G and van der Neut Kolfschoten, M and Zuijdgeest, D and Straetemans, R and Hoffman, RMB and Nieusma, T and Pallesen, J and Turner, HL and Bernard, SM and Ward, AB and Luo, J and Poon, LLM and Tretiakova, AP and Wilson, JM and Limberis, MP and Vogels, R and Brandenburg, B and Kolkman, JA and Wilson, IA}, title = {Universal protection against influenza infection by a multidomain antibody to influenza hemagglutinin.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {598-602}, pmid = {30385580}, issn = {1095-9203}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; R56 AI117675/AI/NIAID NIH HHS/United States ; R56 AI127371/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Neutralizing/chemistry/*immunology/ultrastructure ; Antibodies, Viral/chemistry/*immunology/ultrastructure ; Camelids, New World/*immunology ; Crystallography, X-Ray ; Dogs ; Female ; Hemagglutinin Glycoproteins, Influenza Virus/*immunology ; Immunodominant Epitopes/chemistry/genetics/immunology ; Influenza A virus/*immunology ; Influenza B virus/*immunology ; Influenza Vaccines/*immunology ; Madin Darby Canine Kidney Cells ; Mice ; Mice, Inbred BALB C ; Neutralization Tests ; Orthomyxoviridae Infections/*prevention & control ; Peptide Library ; Recombinant Proteins/chemistry/genetics/immunology ; Single-Domain Antibodies ; }, abstract = {Broadly neutralizing antibodies against highly variable pathogens have stimulated the design of vaccines and therapeutics. We report the use of diverse camelid single-domain antibodies to influenza virus hemagglutinin to generate multidomain antibodies with impressive breadth and potency. Multidomain antibody MD3606 protects mice against influenza A and B infection when administered intravenously or expressed locally from a recombinant adeno-associated virus vector. Crystal and single-particle electron microscopy structures of these antibodies with hemagglutinins from influenza A and B viruses reveal binding to highly conserved epitopes. Collectively, our findings demonstrate that multidomain antibodies targeting multiple epitopes exhibit enhanced virus cross-reactivity and potency. In combination with adeno-associated virus-mediated gene delivery, they may provide an effective strategy to prevent infection with influenza virus and other highly variable pathogens.}, } @article {pmid30385579, year = {2018}, author = {Tso, GHW and Reales-Calderon, JA and Tan, ASM and Sem, X and Le, GTT and Tan, TG and Lai, GC and Srinivasan, KG and Yurieva, M and Liao, W and Poidinger, M and Zolezzi, F and Rancati, G and Pavelka, N}, title = {Experimental evolution of a fungal pathogen into a gut symbiont.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {589-595}, doi = {10.1126/science.aat0537}, pmid = {30385579}, issn = {1095-9203}, mesh = {*Adaptive Immunity ; Animals ; Biological Evolution ; Candida albicans/genetics/growth & development/*immunology/*pathogenicity ; Fungal Proteins/genetics ; Gastrointestinal Microbiome/*immunology ; Gastrointestinal Tract/*microbiology ; *Host-Pathogen Interactions ; Mice ; Mice, Inbred C57BL ; Mutation ; Symbiosis ; Transcription Factors/genetics ; Virulence Factors/genetics ; }, abstract = {Gut microbes live in symbiosis with their hosts, but how mutualistic animal-microbe interactions emerge is not understood. By adaptively evolving the opportunistic fungal pathogen Candida albicans in the mouse gastrointestinal tract, we selected strains that not only had lost their main virulence program but also protected their new hosts against a variety of systemic infections. This protection was independent of adaptive immunity, arose as early as a single day postpriming, was dependent on increased innate cytokine responses, and was thus reminiscent of "trained immunity." Because both the microbe and its new host gain some advantages from their interaction, this experimental system might allow direct study of the evolutionary forces that govern the emergence of mutualism between a mammal and a fungus.}, } @article {pmid30385578, year = {2018}, author = {Mimica, B and Dunn, BA and Tombaz, T and Bojja, VPTNCS and Whitlock, JR}, title = {Efficient cortical coding of 3D posture in freely behaving rats.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {584-589}, doi = {10.1126/science.aau2013}, pmid = {30385578}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Animals ; Back ; Behavior, Animal ; Head ; Imaging, Three-Dimensional ; Models, Animal ; Motor Cortex/*physiology ; Movement/physiology ; Neck ; Neurons/physiology ; Parietal Lobe/*physiology ; Posture/*physiology ; Rats ; }, abstract = {Animals constantly update their body posture to meet behavioral demands, but little is known about the neural signals on which this depends. We therefore tracked freely foraging rats in three dimensions while recording from the posterior parietal cortex (PPC) and the frontal motor cortex (M2), areas critical for movement planning and navigation. Both regions showed strong tuning to posture of the head, neck, and back, but signals for movement were much less dominant. Head and back representations were organized topographically across the PPC and M2, and more neurons represented postures that occurred less often. Simultaneous recordings across areas were sufficiently robust to decode ongoing behavior and showed that spiking in the PPC tended to precede that in M2. Both the PPC and M2 strongly represent posture by using a spatially organized, energetically efficient population code.}, } @article {pmid30385577, year = {2018}, author = {Zhang, H and Griffiths, ML and Chiang, JCH and Kong, W and Wu, S and Atwood, A and Huang, J and Cheng, H and Ning, Y and Xie, S}, title = {East Asian hydroclimate modulated by the position of the westerlies during Termination I.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {580-583}, doi = {10.1126/science.aat9393}, pmid = {30385577}, issn = {1095-9203}, abstract = {Speleothem oxygen isotope records have revolutionized our understanding of the paleo East Asian monsoon, yet there is fundamental disagreement on what they represent in terms of the hydroclimate changes. We report a multiproxy speleothem record of monsoon evolution during the last deglaciation from the middle Yangtze region, which indicates a wetter central eastern China during North Atlantic cooling episodes, despite the oxygen isotopic record suggesting a weaker monsoon. We show that this apparent contradiction can be resolved if the changes are interpreted as a lengthening of the Meiyu rains and shortened post-Meiyu stage, in accordance with a recent hypothesis. Model simulations support this interpretation and further reveal the role of the westerlies in communicating the North Atlantic influence to the East Asian climate.}, } @article {pmid30385576, year = {2018}, author = {Babayan, SA and Orton, RJ and Streicker, DG}, title = {Predicting reservoir hosts and arthropod vectors from evolutionary signatures in RNA virus genomes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {577-580}, doi = {10.1126/science.aap9072}, pmid = {30385576}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Arthropod Vectors/*genetics ; Biodiversity ; Communicable Diseases, Emerging/*prevention & control/virology ; Disease Reservoirs/*virology ; *Epidemiological Monitoring ; Evolution, Molecular ; Genome, Viral ; Genomics ; *Host-Pathogen Interactions ; Humans ; *Machine Learning ; RNA Virus Infections/*prevention & control/virology ; RNA Viruses/*classification/*genetics ; }, abstract = {Identifying the animal origins of RNA viruses requires years of field and laboratory studies that stall responses to emerging infectious diseases. Using large genomic and ecological datasets, we demonstrate that animal reservoirs and the existence and identity of arthropod vectors can be predicted directly from viral genome sequences via machine learning. We illustrate the ability of these models to predict the epidemiology of diverse viruses across most human-infective families of single-stranded RNA viruses, including 69 viruses with previously elusive or never-investigated reservoirs or vectors. Models such as these, which capitalize on the proliferation of low-cost genomic sequencing, can narrow the time lag between virus discovery and targeted research, surveillance, and management.}, } @article {pmid30385575, year = {2018}, author = {Wall, S and Yang, S and Vidas, L and Chollet, M and Glownia, JM and Kozina, M and Katayama, T and Henighan, T and Jiang, M and Miller, TA and Reis, DA and Boatner, LA and Delaire, O and Trigo, M}, title = {Ultrafast disordering of vanadium dimers in photoexcited VO2.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {572-576}, doi = {10.1126/science.aau3873}, pmid = {30385575}, issn = {1095-9203}, abstract = {Many ultrafast solid phase transitions are treated as chemical reactions that transform the structures between two different unit cells along a reaction coordinate, but this neglects the role of disorder. Although ultrafast diffraction provides insights into atomic dynamics during such transformations, diffraction alone probes an averaged unit cell and is less sensitive to randomness in the transition pathway. Using total scattering of femtosecond x-ray pulses, we show that atomic disordering in photoexcited vanadium dioxide (VO2) is central to the transition mechanism and that, after photoexcitation, the system explores a large volume of phase space on a time scale comparable to that of a single phonon oscillation. These results overturn the current understanding of an archetypal ultrafast phase transition and provide new microscopic insights into rapid evolution toward equilibrium in photoexcited matter.}, } @article {pmid30385574, year = {2018}, author = {Blanco-Redondo, A and Bell, B and Oren, D and Eggleton, BJ and Segev, M}, title = {Topological protection of biphoton states.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {568-571}, doi = {10.1126/science.aau4296}, pmid = {30385574}, issn = {1095-9203}, abstract = {The robust generation and propagation of multiphoton quantum states are crucial for applications in quantum information, computing, and communications. Although photons are intrinsically well isolated from the thermal environment, scaling to large quantum optical devices is still limited by scattering loss and other errors arising from random fabrication imperfections. The recent discoveries regarding topological phases have introduced avenues to construct quantum systems that are protected against scattering and imperfections. We experimentally demonstrate topological protection of biphoton states, the building block for quantum information systems. We provide clear evidence of the robustness of the spatial features and the propagation constant of biphoton states generated within a nanophotonics lattice with nontrivial topology and propose a concrete path to build robust entangled states for quantum gates.}, } @article {pmid30385573, year = {2018}, author = {Trost, BM and Huang, Z and Murhade, GM}, title = {Catalytic palladium-oxyallyl cycloaddition.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {564-568}, doi = {10.1126/science.aau4821}, pmid = {30385573}, issn = {1095-9203}, support = {R01 GM033049/GM/NIGMS NIH HHS/United States ; }, abstract = {Exploration of intermediates that enable chemoselective cycloaddition reactions and expeditious construction of fused- or bridged-ring systems is a continuous challenge for organic synthesis. As an intermediate of interest, the oxyallyl cation has been harnessed to synthesize architectures containing seven-membered rings via (4+3) cycloaddition. However, its potential to access five-membered skeletons is underdeveloped, largely due to the thermally forbidden (3+2) pathway. Here, the combination of a tailored precursor and a Pd(0) catalyst generates a Pd-oxyallyl intermediate that cyclizes with conjugated dienes to produce a diverse array of tetrahydrofuran skeletons. The cycloaddition overrides conventional (4+3) selectivity by proceeding through a stepwise pathway involving a Pd-allyl transfer and ring closure sequence. Subsequent treatment of the (3+2) adducts with a palladium catalyst converts the heterocycles to the carbocyclic cyclopentanones.}, } @article {pmid30385572, year = {2018}, author = {Ding, K and Cullen, DA and Zhang, L and Cao, Z and Roy, AD and Ivanov, IN and Cao, D}, title = {A general synthesis approach for supported bimetallic nanoparticles via surface inorganometallic chemistry.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {560-564}, doi = {10.1126/science.aau4414}, pmid = {30385572}, issn = {1095-9203}, abstract = {The synthesis of ultrasmall supported bimetallic nanoparticles (between 1 and 3 nanometers in diameter) with well-defined stoichiometry and intimacy between constituent metals remains a substantial challenge. We synthesized 10 different supported bimetallic nanoparticles via surface inorganometallic chemistry by decomposing and reducing surface-adsorbed heterometallic double complex salts, which are readily obtained upon sequential adsorption of target cations and anions on a silica substrate. For example, adsorption of tetraamminepalladium(II) [Pd(NH3)42+] followed by adsorption of tetrachloroplatinate [PtCl42-] was used to form palladium-platinum (Pd-Pt) nanoparticles. These supported bimetallic nanoparticles show enhanced catalytic performance in acetylene selective hydrogenation, which clearly demonstrates a synergistic effect between constituent metals.}, } @article {pmid30385571, year = {2018}, author = {Kinloch, IA and Suhr, J and Lou, J and Young, RJ and Ajayan, PM}, title = {Composites with carbon nanotubes and graphene: An outlook.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {547-553}, doi = {10.1126/science.aat7439}, pmid = {30385571}, issn = {1095-9203}, abstract = {Composite materials with carbon nanotube and graphene additives have long been considered as exciting prospects among nanotechnology applications. However, after nearly two decades of work in the area, questions remain about the practical impact of nanotube and graphene composites. This uncertainty stems from factors that include poor load transfer, interfacial engineering, dispersion, and viscosity-related issues that lead to processing challenges in such nanocomposites. Moreover, there has been little effort to identify selection rules for the use of nanotubes or graphene in composite matrices for specific applications. This review is a critical look at the status of composites for developing high-strength, low-density, high-conductivity materials with nanotubes or graphene. An outlook of the different approaches that can lead to practically useful nanotube and graphene composites is presented, pointing out the challenges and opportunities that exist in the field.}, } @article {pmid30385570, year = {2018}, author = {Eder, M and Amini, S and Fratzl, P}, title = {Biological composites-complex structures for functional diversity.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {543-547}, doi = {10.1126/science.aat8297}, pmid = {30385570}, issn = {1095-9203}, mesh = {Biocompatible Materials/*chemical synthesis/*chemistry ; Bioengineering ; Green Chemistry Technology ; Minerals/*chemistry ; Proteins/*chemistry ; Sugars/*chemistry ; }, abstract = {The bulk of Earth's biological materials consist of few base substances-essentially proteins, polysaccharides, and minerals-that assemble into large varieties of structures. Multifunctionality arises naturally from this structural complexity: An example is the combination of rigidity and flexibility in protein-based teeth of the squid sucker ring. Other examples are time-delayed actuation in plant seed pods triggered by environmental signals, such as fire and water, and surface nanostructures that combine light manipulation with mechanical protection or water repellency. Bioinspired engineering transfers some of these structural principles into technically more relevant base materials to obtain new, often unexpected combinations of material properties. Less appreciated is the huge potential of using bioinspired structural complexity to avoid unnecessary chemical diversity, enabling easier recycling and, thus, a more sustainable materials economy.}, } @article {pmid30385569, year = {2018}, author = {Mohanty, AK and Vivekanandhan, S and Pin, JM and Misra, M}, title = {Composites from renewable and sustainable resources: Challenges and innovations.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {536-542}, doi = {10.1126/science.aat9072}, pmid = {30385569}, issn = {1095-9203}, mesh = {Biocompatible Materials/*chemistry ; Biodegradation, Environmental ; *Green Chemistry Technology ; }, abstract = {Interest in constructing composite materials from biosourced, recycled materials; waste resources; and their combinations is growing. Biocomposites have attracted the attention of automakers for the design of lightweight parts. Hybrid biocomposites made of petrochemical-based and bioresourced materials have led to technological advances in manufacturing. Greener biocomposites from plant-derived fiber and crop-derived plastics with higher biobased content are continuously being developed. Biodegradable composites have shown potential for major uses in sustainable packaging. Recycled plastic materials originally destined for landfills can be redirected and repurposed for blending in composite applications, thus leading to reduced dependence on virgin petro-based materials. Studies on compatibility of recycled and waste materials with other components in composite structure for improved interface and better mechanical performance pose major scientific challenges. This research holds the promise of advancing a key global sustainability goal.}, } @article {pmid30385568, year = {2018}, author = {Lavine, M and Grocholski, B}, title = {Mixing and matching materials.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {534-535}, doi = {10.1126/science.aav7390}, pmid = {30385568}, issn = {1095-9203}, } @article {pmid30385567, year = {2018}, author = {Croft, DA}, title = {Evolution of teeth in South America.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {533}, doi = {10.1126/science.aav6745}, pmid = {30385567}, issn = {1095-9203}, mesh = {Biological Evolution ; *Fossils ; Phylogeny ; South America ; *Tooth ; }, } @article {pmid30385566, year = {2018}, author = {Delborne, J and Kokotovich, A and Barnhill-Dilling, SK}, title = {Engaging community with humility.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {532-533}, doi = {10.1126/science.aav4987}, pmid = {30385566}, issn = {1095-9203}, mesh = {*Stakeholder Participation ; }, } @article {pmid30385565, year = {2018}, author = {Horner-Devine, MC and Gonsalves, T and Margherio, C and Mizumori, SJ and Yen, JW}, title = {Beyond hierarchical one-on-one mentoring.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {532}, doi = {10.1126/science.aav7656}, pmid = {30385565}, issn = {1095-9203}, mesh = {*Mentoring ; *Mentors ; }, } @article {pmid30385564, year = {2018}, author = {Kofler, N and Collins, JP and Kuzma, J and Marris, E and Esvelt, K and Nelson, MP and Newhouse, A and Rothschild, LJ and Vigliotti, VS and Semenov, M and Jacobsen, R and Dahlman, JE and Prince, S and Caccone, A and Brown, T and Schmitz, OJ}, title = {Editing nature: Local roots of global governance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {527-529}, doi = {10.1126/science.aat4612}, pmid = {30385564}, issn = {1095-9203}, mesh = {Animals ; Anthozoa/genetics ; *Bioethical Issues ; *CRISPR-Cas Systems ; Conservation of Natural Resources/*methods ; Coral Reefs ; Gene Editing/*ethics/*methods ; *Gene-Environment Interaction ; }, } @article {pmid30385563, year = {2018}, author = {Cavalleri, A}, title = {Disorder at the border.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {525-526}, doi = {10.1126/science.aav2019}, pmid = {30385563}, issn = {1095-9203}, } @article {pmid30385562, year = {2018}, author = {Woolhouse, M}, title = {Sources of human viruses.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {524-525}, doi = {10.1126/science.aav4265}, pmid = {30385562}, issn = {1095-9203}, mesh = {Humans ; *Viruses ; }, } @article {pmid30385561, year = {2018}, author = {d'Enfert, C}, title = {Evolving a pathogen to be protective.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {523-524}, doi = {10.1126/science.aav3374}, pmid = {30385561}, issn = {1095-9203}, mesh = {*Host-Pathogen Interactions ; }, } @article {pmid30385560, year = {2018}, author = {Brundin, P and Wyse, R}, title = {Cancer enzyme affects Parkinson's disease.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {521-522}, doi = {10.1126/science.aav3986}, pmid = {30385560}, issn = {1095-9203}, mesh = {Humans ; Neoplasms/*enzymology ; *Parkinson Disease ; Poly Adenosine Diphosphate Ribose/*metabolism ; }, } @article {pmid30385559, year = {2018}, author = {Chen, G}, title = {Identifying posture cells in the brain.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {520-521}, doi = {10.1126/science.aav3819}, pmid = {30385559}, issn = {1095-9203}, mesh = {*Brain ; *Posture ; }, } @article {pmid30385558, year = {2018}, author = {McGee, D}, title = {Shifting summer rains.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {518-520}, doi = {10.1126/science.aav5280}, pmid = {30385558}, issn = {1095-9203}, mesh = {*Rain ; *Seasons ; }, } @article {pmid30385557, year = {2018}, author = {Voosen, P}, title = {Moments to spare.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {514-517}, doi = {10.1126/science.362.6414.514}, pmid = {30385557}, issn = {1095-9203}, } @article {pmid30385556, year = {2018}, author = {Kaiser, J}, title = {Suspect science leads to pause in stem cell trial.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {513}, doi = {10.1126/science.362.6414.513}, pmid = {30385556}, issn = {1095-9203}, mesh = {Clinical Trials as Topic ; Heart Diseases/*therapy ; Humans ; Myocardium ; Regeneration ; *Scientific Misconduct ; *Stem Cell Transplantation ; *Stem Cells ; }, } @article {pmid30385555, year = {2018}, author = {Cartlidge, E}, title = {Europe's €1 billion quantum flagship announces grants.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {512}, doi = {10.1126/science.362.6414.512}, pmid = {30385555}, issn = {1095-9203}, } @article {pmid30385554, year = {2018}, author = {Cohen, J}, title = {Llama antibodies inspire gene spray to prevent all flus.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {511}, doi = {10.1126/science.362.6414.511}, pmid = {30385554}, issn = {1095-9203}, } @article {pmid30385553, year = {2018}, author = {Rabesandratana, T}, title = {Microbiome conservancy stores global fecal samples.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {510-511}, doi = {10.1126/science.362.6414.510}, pmid = {30385553}, issn = {1095-9203}, mesh = {Feces/*microbiology ; Humans ; *Microbiota ; Niger ; *Preservation, Biological ; Rwanda ; *Specimen Handling ; }, } @article {pmid30385552, year = {2018}, author = {Service, RF}, title = {Advances in flow batteries promise cheap backup power.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {508-509}, doi = {10.1126/science.362.6414.508}, pmid = {30385552}, issn = {1095-9203}, } @article {pmid30385551, year = {2018}, author = {Rosen, J}, title = {Seafloor mappers to compete for XPRIZE.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {507-508}, doi = {10.1126/science.362.6414.507}, pmid = {30385551}, issn = {1095-9203}, } @article {pmid30385550, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {504-506}, doi = {10.1126/science.362.6414.504}, pmid = {30385550}, issn = {1095-9203}, } @article {pmid30385549, year = {2018}, author = {Shah, T and Ray, C and Lele, U}, title = {How to clean up the Ganges?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {503}, doi = {10.1126/science.aav8261}, pmid = {30385549}, issn = {1095-9203}, mesh = {*Environmental Restoration and Remediation ; India ; *Rivers ; *Sewage ; Sri Lanka ; Water Pollution/*prevention & control ; }, } @article {pmid30385548, year = {2018}, author = {Kam, TI and Mao, X and Park, H and Chou, SC and Karuppagounder, SS and Umanah, GE and Yun, SP and Brahmachari, S and Panicker, N and Chen, R and Andrabi, SA and Qi, C and Poirier, GG and Pletnikova, O and Troncoso, JC and Bekris, LM and Leverenz, JB and Pantelyat, A and Ko, HS and Rosenthal, LS and Dawson, TM and Dawson, VL}, title = {Poly(ADP-ribose) drives pathologic α-synuclein neurodegeneration in Parkinson's disease.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {}, doi = {10.1126/science.aat8407}, pmid = {30385548}, issn = {1095-9203}, support = {R37 NS067525/NS/NINDS NIH HHS/United States ; U01 NS100610/NS/NINDS NIH HHS/United States ; U01 NS082133/NS/NINDS NIH HHS/United States ; R01 NS082205/NS/NINDS NIH HHS/United States ; U01 NS097049/NS/NINDS NIH HHS/United States ; P50 NS038377/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Benzimidazoles/pharmacology ; Brain/metabolism/pathology ; Cell Death ; Dopaminergic Neurons/metabolism/pathology ; Enzyme Activation ; Gene Knockout Techniques ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nitric Oxide/metabolism ; Parkinson Disease/*metabolism/*pathology ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors/genetics/*metabolism ; Poly Adenosine Diphosphate Ribose/*metabolism ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Recombinant Proteins/genetics/metabolism ; alpha-Synuclein/genetics/*metabolism ; }, abstract = {The pathologic accumulation and aggregation of α-synuclein (α-syn) underlies Parkinson's disease (PD). The molecular mechanisms by which pathologic α-syn causes neurodegeneration in PD are not known. Here, we found that pathologic α-syn activates poly(adenosine 5'-diphosphate-ribose) (PAR) polymerase-1 (PARP-1), and PAR generation accelerates the formation of pathologic α-syn, resulting in cell death via parthanatos. PARP inhibitors or genetic deletion of PARP-1 prevented pathologic α-syn toxicity. In a feed-forward loop, PAR converted pathologic α-syn to a more toxic strain. PAR levels were increased in the cerebrospinal fluid and brains of patients with PD, suggesting that PARP activation plays a role in PD pathogenesis. Thus, strategies aimed at inhibiting PARP-1 activation could hold promise as a disease-modifying therapy to prevent the loss of dopamine neurons in PD.}, } @article {pmid30385547, year = {2018}, author = {Cheng, Z and Zhou, H and Lu, Q and Gao, H and Lu, L}, title = {Extra strengthening and work hardening in gradient nanotwinned metals.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {}, doi = {10.1126/science.aau1925}, pmid = {30385547}, issn = {1095-9203}, abstract = {Gradient structures exist ubiquitously in nature and are increasingly being introduced in engineering. However, understanding structural gradient-related mechanical behaviors in all gradient structures, including those in engineering materials, has been challenging. We explored the mechanical performance of a gradient nanotwinned structure with highly tunable structural gradients in pure copper. A large structural gradient allows for superior work hardening and strength that can exceed those of the strongest component of the gradient structure. We found through systematic experiments and atomistic simulations that this unusual behavior is afforded by a unique patterning of ultrahigh densities of dislocations in the grain interiors. These observations not only shed light on gradient structures, but may also indicate a promising route for improving the mechanical properties of materials through gradient design.}, } @article {pmid30385546, year = {2018}, author = {Sievers, QL and Petzold, G and Bunker, RD and Renneville, A and Słabicki, M and Liddicoat, BJ and Abdulrahman, W and Mikkelsen, T and Ebert, BL and Thomä, NH}, title = {Defining the human C2H2 zinc finger degrome targeted by thalidomide analogs through CRBN.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {}, doi = {10.1126/science.aat0572}, pmid = {30385546}, issn = {1095-9203}, support = {P50 CA206963/CA/NCI NIH HHS/United States ; R01 HL082945/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P01 CA066996/CA/NCI NIH HHS/United States ; R01 HL082941/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; *CYS2-HIS2 Zinc Fingers ; HEK293 Cells ; Humans ; Ikaros Transcription Factor/metabolism ; Lenalidomide/*pharmacology ; Peptide Hydrolases/*metabolism ; Proteolysis/*drug effects ; Proteome/metabolism ; Thalidomide/*analogs & derivatives/pharmacology ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination/*drug effects ; }, abstract = {The small molecules thalidomide, lenalidomide, and pomalidomide induce the ubiquitination and proteasomal degradation of the transcription factors Ikaros (IKZF1) and Aiolos (IKZF3) by recruiting a Cys2-His2 (C2H2) zinc finger domain to Cereblon (CRBN), the substrate receptor of the CRL4CRBN E3 ubiquitin ligase. We screened the human C2H2 zinc finger proteome for degradation in the presence of thalidomide analogs, identifying 11 zinc finger degrons. Structural and functional characterization of the C2H2 zinc finger degrons demonstrates how diverse zinc finger domains bind the permissive drug-CRBN interface. Computational zinc finger docking and biochemical analysis predict that more than 150 zinc fingers bind the drug-CRBN complex in vitro, and we show that selective zinc finger degradation can be achieved through compound modifications. Our results provide a rationale for therapeutically targeting transcription factors that were previously considered undruggable.}, } @article {pmid30385465, year = {2018}, author = {Ablain, J and Xu, M and Rothschild, H and Jordan, RC and Mito, JK and Daniels, BH and Bell, CF and Joseph, NM and Wu, H and Bastian, BC and Zon, LI and Yeh, I}, title = {Human tumor genomics and zebrafish modeling identify SPRED1 loss as a driver of mucosal melanoma.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1055-1060}, doi = {10.1126/science.aau6509}, pmid = {30385465}, issn = {1095-9203}, support = {R35 CA220481/CA/NCI NIH HHS/United States ; R01 CA103846/CA/NCI NIH HHS/United States ; K99 CA201465/CA/NCI NIH HHS/United States ; U24 CA196067/CA/NCI NIH HHS/United States ; T32 HL007627/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Melanomas originating from mucosal surfaces have low mutation burden, genomic instability, and poor prognosis. To identify potential driver genes, we sequenced hundreds of cancer-related genes in 43 human mucosal melanomas, cataloging point mutations, amplifications, and deletions. The SPRED1 gene, which encodes a negative regulator of mitogen-activated protein kinase (MAPK) signaling, was inactivated in 37% of the tumors. Four distinct genotypes were associated with SPRED1 loss. Using a rapid, tissue-specific CRISPR technique to model these genotypes in zebrafish, we found that SPRED1 functions as a tumor suppressor, particularly in the context of KIT mutations. SPRED1 knockdown caused MAPK activation, increased cell proliferation, and conferred resistance to drugs inhibiting KIT tyrosine kinase activity. These findings provide a rationale for MAPK inhibition in SPRED1-deficient melanomas and introduce a zebrafish modeling approach that can be used more generally to dissect genetic interactions in cancer.}, } @article {pmid30385464, year = {2018}, author = {Moffitt, JR and Bambah-Mukku, D and Eichhorn, SW and Vaughn, E and Shekhar, K and Perez, JD and Rubinstein, ND and Hao, J and Regev, A and Dulac, C and Zhuang, X}, title = {Molecular, spatial, and functional single-cell profiling of the hypothalamic preoptic region.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {}, doi = {10.1126/science.aau5324}, pmid = {30385464}, issn = {1095-9203}, support = {R01 MH113094/MH/NIMH NIH HHS/United States ; R01 MH111502/MH/NIMH NIH HHS/United States ; R01 HD082131/HD/NICHD NIH HHS/United States ; K99 HD092542/HD/NICHD NIH HHS/United States ; K99 EY028625/EY/NEI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {The hypothalamus controls essential social behaviors and homeostatic functions. However, the cellular architecture of hypothalamic nuclei-including the molecular identity, spatial organization, and function of distinct cell types-is poorly understood. Here, we developed an imaging-based in situ cell-type identification and mapping method and combined it with single-cell RNA-sequencing to create a molecularly annotated and spatially resolved cell atlas of the mouse hypothalamic preoptic region. We profiled ~1 million cells, identified ~70 neuronal populations characterized by distinct neuromodulatory signatures and spatial organizations, and defined specific neuronal populations activated during social behaviors in male and female mice, providing a high-resolution framework for mechanistic investigation of behavior circuits. The approach described opens a new avenue for the construction of cell atlases in diverse tissues and organisms.}, } @article {pmid30385309, year = {2019}, author = {Gerlach, ADCL and Toprak, Z and Naciri, Y and Caviró, EA and da Silveira, RMB and Clerc, P}, title = {New insights into the Usnea cornuta aggregate (Parmeliaceae, lichenized Ascomycota): Molecular analysis reveals high genetic diversity correlated with chemistry.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {125-137}, doi = {10.1016/j.ympev.2018.10.035}, pmid = {30385309}, issn = {1095-9513}, abstract = {Biological processes such as hybridization, incomplete lineage sorting and gene flow can obscure the recognition of distinct evolutionary lineages, particularly in groups of organisms that have recently diverged. Therefore, compiling pieces of evidence from diverse data sources is critical to accurately assess species boundaries in such groups. The increasing availability of DNA sequence data allows for a much deeper understanding of diversification and speciation processes and their consequences on biodiversity. In this study, we applied an integrative approach based on DNA sequence, chemical, geographic and morphological data to attempt to define species boundaries in the lichen-forming genus Usnea (Parmeliaceae), particularly the U. cornuta aggregate, a cosmopolitan species group. We provide the first species delimitation for this group in the neotropics based on the multispecies coalescent (MSC) model. Using ITS rDNA and two protein-coding genes, Mcm7 and RPB1, we estimated the species tree under the MSC model in a Bayesian framework using STACEY. Our results indicate that at least nine strongly supported distinct lineages coexist in the U. cornuta aggregate, which are well chemically characterized. Additionally, we found evidence for the polyphyly of three morphospecies, Usnea brasiliensis, U. cornuta and U. dasaea.}, } @article {pmid30385308, year = {2019}, author = {Crouch, NMA and Ramanauskas, K and Igić, B}, title = {Tip-dating and the origin of Telluraves.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {55-63}, doi = {10.1016/j.ympev.2018.10.006}, pmid = {30385308}, issn = {1095-9513}, abstract = {Despite a relatively vast accumulation of molecular data, the timing of diversification of modern bird lineages remains elusive. Accurate dating of the origination of Telluraves-a clade of birds defined by their arboreality-is of particular interest, as it contains the most species-rich avian group, the passerines. Historically, neontological studies have estimated a Cretaceous origin for the group, but more recent studies have recovered Cenozoic dates, closer to the oldest known fossils for the group. We employ total-evidence dating to estimate divergence times that are expected to be both less sensitive to prior assumptions and more accurate. Specifically, we use a large collection of morphological character data from arboreal bird fossils, along with combined molecular sequence and morphological character data from extant taxa. Our analyses recover a Late Cretaceous origin for crown Telluraves, with a few lineages crossing the K-Pg boundary. Following the K-Pg boundary, our results show the group underwent rapid diversification, likely benefiting from increased ecological opportunities in the aftermath of the extinction event. We find very little confidence for the precise topological placement of many extinct taxa, possibly due to rapid diversification, paucity of character data, and rapid morphological differentiation during the early history of the group.}, } @article {pmid30385275, year = {2018}, author = {Rosner, A and Kravchenko, O and Rinkevich, B}, title = {IAP genes partake weighty roles in the astogeny and whole body regeneration in the colonial urochordate Botryllus schlosseri.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.10.015}, pmid = {30385275}, issn = {1095-564X}, abstract = {Inhibitors of Apoptosis Protein (IAP) genes participate in processes like apoptosis, proliferation, innate immunity, inflammation, cell motility, differentiation and in malignancies. Here we reveal 25 IAP genes in the tunicate Botryllus schlosseri's genome and their functions in two developmental biology phenomena, a new mode of whole body regeneration (WBR) induced by budectomy, and blastogenesis, the four-staged cycles of botryllid ascidian astogeny. IAP genes that were specifically upregulated during these developmental phenomena were identified, and protein expression patterns of one of these genes, IAP28, were followed. Most of the IAP genes upregulation recorded at blastogenetic stages C/D was in concert with the upregulation at 100 μM H2O2 apoptotic-induced treatment and in parallel to expressions of AIF1, Bax, Mcl1, caspase 2 and two orthologues of caspase 7. Wnt agonist altered the takeover duration along with reduced IAP expressions, and displacement of IAP28+ phagocytes. WBR was initiated solely at blastogenetic stage D, where zooidal absorption was attenuated and regeneration centers were formed either from remains of partially absorbed zooids or from deformed ampullae. Subsequently, bud-bearing zooids developed, in concert with a massive IAP28-dependent phagocytic wave that eliminated the old zooids, then proceeded with the establishment of morphologically normal-looking colonies. IAP4, IAP14 and IAP28 were also involved in WBR, in conjunction with the expression of the pro-survival PI3K-Akt pathway. IAPs function deregulation by Smac mimetics resulted in severe morphological damages, attenuation in bud growth and differentiation, and in destabilization of colonial coordination. Longtime knockdown of IAP functions prior to the budectomy, resulted in colonial death.}, } @article {pmid30385274, year = {2019}, author = {Handara, G and Hetsch, FJA and Jüttner, R and Schick, A and Haupt, C and Rathjen, FG and Kröger, S}, title = {The role of agrin, Lrp4 and MuSK during dendritic arborization and synaptogenesis in cultured embryonic CNS neurons.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {54-67}, doi = {10.1016/j.ydbio.2018.10.017}, pmid = {30385274}, issn = {1095-564X}, abstract = {The role of agrin, Lrp4 and MuSK, key organizers of neuromuscular synaptogenesis, in the developing CNS is only poorly understood. We investigated the role of these proteins in cultured mouse embryonic cortical neurons from wildtype and from Lrp4- and MuSK-deficient mice. Neurons from Lrp4-deficient mice had fewer but longer primary dendrites and a decreased density of puncta containing excitatory and inhibitory synapse-associated proteins. Neurons from MuSK-deficient mice had an altered dendritic branching pattern but no change in the density of puncta stained by antibodies against synapse-associated proteins. Transfection of TM-agrin compensated the dendritic branching deficits in Lrp4-deficient but not in MuSK-deficient neurons. TM-agrin transfection increased the density of excitatory synaptic puncta in MuSK-deficient but not in Lrp4-deficient mice and reduced the number of inhibitory synaptic puncta irrespective of MuSK and Lrp4 expression. Addition of purified soluble agrin to microisland cultures of cortical neurons revealed an Lrp4-dependent increase in the size and density of glutamatergic synaptic puncta and in mEPSC but not in mIPSC frequency and amplitude. Thus, agrin induced an Lrp4-independent increase in dendritic branch complexity, an Lrp4-dependent increase of excitatory synaptic puncta and an Lrp4- and MuSK-independent decrease in the density of puncta containing inhibitory synapse-associated proteins. These results establish selective roles for agrin, Lrp4 and MuSK during dendritogenesis and synaptogenesis in cultured CNS neurons.}, } @article {pmid30385203, year = {2018}, author = {Kaiser, MI}, title = {ENCODE and the parts of the human genome.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {72}, number = {}, pages = {28-37}, doi = {10.1016/j.shpsc.2018.10.008}, pmid = {30385203}, issn = {1879-2499}, mesh = {*Genome, Human ; Genomics ; Humans ; *Metaphysics ; *Molecular Sequence Annotation ; *Transcription, Genetic ; }, abstract = {This paper examines a specific kind of part-whole relations that exist in the molecular genetic domain. The central question is under which conditions a particular molecule, such as a DNA sequence, is a biological part of the human genome. I address this question by analyzing how biologists in fact partition the human genome into parts. This paper thus presents a case study in the metaphysics of biological practice. I develop a metaphysical account of genomic parthood by analyzing the investigative and reasoning practices in the ENCODE (ENCyclopedia Of DNA Elements) project. My account reveals two conditions that determine whether a molecule is a part of the human genome (i.e., a genomic part). First, genomic parts must possess a causal role function in the genome as a whole, that is, their functions must contribute to the genome directing the overall functioning of the cell. Second, genomic parts must have a specific chemical structure and be actual segments of the DNA sequence of the genome.}, } @article {pmid30385077, year = {2018}, author = {Hoegh-Guldberg, O and Kennedy, EV and Beyer, HL and McClennen, C and Possingham, HP}, title = {Securing a Long-term Future for Coral Reefs.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {936-944}, doi = {10.1016/j.tree.2018.09.006}, pmid = {30385077}, issn = {1872-8383}, abstract = {Rapid ocean warming as a result of climate change poses a key risk for coral reefs. Even if the goals of the Paris Climate Agreement are achieved, coral reefs are likely to decline by 70-90% relative to their current abundance by midcentury. Although alarming, coral communities that survive will play a key role in the regeneration of reefs by mid-to-late century. Here, we argue for a coordinated, global coral reef conservation strategy that is centred on 50 large (500km2) regions that are the least vulnerable to climate change and which are positioned to facilitate future coral reef regeneration. The proposed strategy and actions should strengthen and expand existing conservation efforts for coral reefs as we face the long-term consequences of intensifying climate change.}, } @article {pmid30384859, year = {2018}, author = {Zaid, Y and Senhaji, N and Bakhtaoui, FZ and Serrano, A and Serbati, N and Karkouri, M and Badre, W and Oudghiri, M and Martin, J and Nadifi, S}, title = {The PTPN22 C1858T (R620W) functional polymorphism in inflammatory bowel disease.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {783}, pmid = {30384859}, issn = {1756-0500}, abstract = {OBJECTIVE: In view of the discrepant data regarding the association between the protein tyrosine phosphatase non-receptor 22 (PTPN22) rs2476601 (R620W, 1858C→T) polymorphism and susceptibility to autoimmune diseases including inflammatory bowel diseases (IBD), we investigated whether this functional single-nucleotide polymorphism influences IBD risk in a group of Moroccan patients.

RESULTS: This is the first report on the prevalence of PTPN22 (R620W) variant in a Moroccan cohort. No evidence of statistically significant differences was observed when the PTPN22 (R620W) allele and genotype distribution among IBD, Crohn's disease (CD), ulcerative colitis (UC) patients and healthy controls were compared. The frequency of the variant allele in healthy subjects was 1.77% compared to 2.56% in the IBD patients and 1.85% in CD patients. Furthermore, the frequency of this allele was increased in UC patients compared to controls (4.17% vs. 1.77%, OR = 2.42, 95% CI 0.82-7.08; P = 0.09), but the difference was not statistically significant. Our data suggest a lack of association between PTPN22 R620W variant and IBD susceptibility in Moroccan patients.}, } @article {pmid30384854, year = {2018}, author = {Hayashi, S and Yamaguchi, R and Mizuno, S and Komura, M and Miyano, S and Nakagawa, H and Imoto, S}, title = {ALPHLARD: a Bayesian method for analyzing HLA genes from whole genome sequence data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {790}, pmid = {30384854}, issn = {1471-2164}, support = {15H02775//Japan Society for the Promotion of Science/ ; 15H05912//Japan Society for the Promotion of Science/ ; }, abstract = {BACKGROUND: Although human leukocyte antigen (HLA) genotyping based on amplicon, whole exome sequence (WES), and RNA sequence data has been achieved in recent years, accurate genotyping from whole genome sequence (WGS) data remains a challenge due to the low depth. Furthermore, there is no method to identify the sequences of unknown HLA types not registered in HLA databases.

RESULTS: We developed a Bayesian model, called ALPHLARD, that collects reads potentially generated from HLA genes and accurately determines a pair of HLA types for each of HLA-A, -B, -C, -DPA1, -DPB1, -DQA1, -DQB1, and -DRB1 genes at 3rd field resolution. Furthermore, ALPHLARD can detect rare germline variants not stored in HLA databases and call somatic mutations from paired normal and tumor sequence data. We illustrate the capability of ALPHLARD using 253 WES data and 25 WGS data from Illumina platforms. By comparing the results of HLA genotyping from SBT and amplicon sequencing methods, ALPHLARD achieved 98.8% for WES data and 98.5% for WGS data at 2nd field resolution. We also detected three somatic point mutations and one case of loss of heterozygosity in the HLA genes from the WGS data.

CONCLUSIONS: ALPHLARD showed good performance for HLA genotyping even from low-coverage data. It also has a potential to detect rare germline variants and somatic mutations in HLA genes. It would help to fill in the current gaps in HLA reference databases and unveil the immunological significance of somatic mutations identified in HLA genes.}, } @article {pmid30384853, year = {2018}, author = {Lu, N and Mei, F and Wang, Z and Wang, N and Xiao, Y and Kong, L and Qu, G and Ma, W and Wang, J}, title = {Single-nucleotide polymorphisms(SNPs) in a sucrose synthase gene are associated with wood properties in Catalpa fargesii bur.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {99}, pmid = {30384853}, issn = {1471-2156}, support = {201404101//Forestry Industry Research Special Funds for Public Welfare Projects/ ; }, abstract = {BACKGROUND: Association study is a powerful means for identifying molecular markers, such as single-nucleotide polymorphisms (SNPs) associated with important traits in forest trees. Catalpa fargesii Bur is a valuable commercial tree in China and identifying SNPs that associate with wood property would make a foundation of the marker-assisted breeding in the future. However, related work has not been reported yet.

RESULTS: We cloned a 2887 bp long sucrose synthase (SUS) gene from the genome of C. fargesii, which is a key enzyme in sucrose metabolism and also associated to wood formation in trees, coding 806 amino acids that expressed mainly in young branches, xylem, and leaves according to real-time quantitative PCR. Then we identified allelic variations of CfSUS associated with nine wood quality associated traits in Catalpa fargesii Bur. Totally, 135 SNPs were identified through cloning and sequencing the CfSUS locus from a mapping population (including 93 unrelated individuals) and 47 of which were genotyped as common SNPs (minor allele frequency > 5%) in the association population that comprised of 125 unrelated individuals collected from main distribution area. Nucleotide diversity and linkage disequilibrium (LD) analysis showed CfSUS has a relative low SNP diversity (πT = 0.0034) and low LD (r2 dropped below 0.1 within 1600 bp). Using the association analysis, we found 11 common SNPs and 14 haplotypes were significantly associated with the traits (false discovery rate, Q<0.1), explaining 3.21-12.41% of the phenotypic variance. These results provide molecular markers above associated with wood basic density, pore rate, and six other traits of wood, which have potential applications in breeding of Catalpa fargesii Bur.

CONCLUSION: We first cloned a SUS gene in C. fargesii, then identified several SNPs and haplotypes that associated with wood properties within this gene, suggesting CfSUS participates in the wood formation of C. fargesii. Moreover, molecular markers we identified in this study may be applied into marker-assisted breeding of C. fargesii in the future.}, } @article {pmid30384851, year = {2018}, author = {Horodyska, J and Wimmers, K and Reyer, H and Trakooljul, N and Mullen, AM and Lawlor, PG and Hamill, RM}, title = {RNA-seq of muscle from pigs divergent in feed efficiency and product quality identifies differences in immune response, growth, and macronutrient and connective tissue metabolism.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {791}, pmid = {30384851}, issn = {1471-2164}, support = {No. 311794//FP7 International Cooperation/ ; }, abstract = {BACKGROUND: Feed efficiency (FE) is an indicator of efficiency in converting energy and nutrients from feed into a tissue that is of major environmental and economic significance. The molecular mechanisms contributing to differences in FE are not fully elucidated, therefore the objective of this study was to profile the porcine Longissimus thoracis et lumborum (LTL) muscle transcriptome, examine the product quality from pigs divergent in FE and investigate the functional networks underpinning the potential relationship between product quality and FE.

RESULTS: RNA-Seq (n = 16) and product quality (n = 40) analysis were carried out in the LTL of pigs differing in FE status. A total of 272 annotated genes were differentially expressed with a P < 0.01. Functional annotation revealed a number of biological events related to immune response, growth, carbohydrate & lipid metabolism and connective tissue indicating that these might be the key mechanisms governing differences in FE. Five most significant bio-functions altered in FE groups were 'haematological system development & function', 'lymphoid tissue structure & development', 'tissue morphology', 'cellular movement' and 'immune cell trafficking'. Top significant canonical pathways represented among the differentially expressed genes included 'IL-8 signalling', 'leukocyte extravasation signalling, 'sphingosine-1-phosphate signalling', 'PKCθ signalling in T lymphocytes' and 'fMLP signalling in neutrophils'. A minor impairment in the quality of meat, in relation to texture and water-holding capacity, produced by high-FE pigs was observed. High-FE pigs also had reduced intramuscular fat content and improved nutritional profile in terms of fatty acid composition.

CONCLUSIONS: Ontology analysis revealed enhanced activity of adaptive immunity and phagocytes in high-FE pigs suggesting more efficient conserving of resources, which can be utilised for other important biological processes. Shifts in carbohydrate conversion into glucose in FE-divergent muscle may underpin the divergent evolution of pH profile in meat from the FE-groups. Moreover, altered amino acid metabolism and increased mobilisation & flux of calcium may influence growth in FE-divergent muscle. Furthermore, decreased degradation of fibroblasts in FE-divergent muscle could impact on collagen turnover and alter tenderness of meat, whilst enhanced lipid degradation in high-FE pigs may potentially underlie a more efficient fat metabolism in these animals.}, } @article {pmid30384838, year = {2018}, author = {Lin, L and Yang, Z and Zheng, G and Zhuansun, Y and Wang, Y and Li, J and Chen, R and Tang, W}, title = {Analyses of changes in myocardial long non-coding RNA and mRNA profiles after severe hemorrhagic shock and resuscitation via RNA sequencing in a rat model.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {11}, pmid = {30384838}, issn = {1471-2199}, support = {No. 81000-42020004//a project of Leading Talents in Pearl River Talent Plan of Guangdong Province/ ; No. 201804010471//Guangzhou Science and Technology Plan/ ; }, abstract = {BACKGROUND: Ischemia-reperfusion injury has been proven to induce organ dysfunction and death, although the mechanism is not fully understood. Long non-coding RNAs (lncRNAs) have drawn wide attention with their important roles in the gene expression of some biological processes and diseases, including myocardial ischemia-reperfusion (I/R) injury. In this paper, a total of 26 Sprague-Dawley (SD) rats were randomized into two groups: sham and ischemia-reperfusion (I/R) injury. Hemorrhagic shock was induced by removing 45% of the estimated total blood volume followed by reinfusion of shed blood. High-throughput RNA sequencing was used to analyze differentially expressed (DE) lncRNAs and messenger RNAs (mRNAs) in the heart tissue 4 h after reperfusion. Myocardial function was also evaluated.

RESULTS: After resuscitation, the decline of myocardial function of shocked animals, expressed by cardiac output, ejection fraction, and myocardial performance index (MPI), was significant (p < 0.05). DE lncRNAs and mRNAs were identified by absolute value of fold change ≥ 2 and the false discovery rate ≤ 0.001. In rats from the I/R injury group, 851 lncRNAs and 1015 mRNAs were significantly up-regulated while 1533 lncRNAs and 1702 m RNAs were significantly down-regulated when compared to the sham group. Among the DE lncRNAs, we found 12 location-associated with some known apoptosis-related protein-coding genes which were up-regulated or down-regulated accordingly, including STAT3 and Il1r1. Real time PCR assays confirmed that the expression levels of five location-associated lncRNAs (NONRATT006032.2, NONRATT006033.2, NONRATT006034.2, NONRATT006035.2 and NONRATT029969.2) and their location-associated mRNAs (STAT3 and Il1r1) in the rats from the I/R injury group were all significantly up-regulated versus the sham group.

CONCLUSIONS: The DE lncRNAs (NONRATT006032.2, NONRATT006033.2, NONRATT006034.2 and NONRATT006035.2) could be compatible with their role in myocardial protection by stimulating their co-located gene (STAT3) after hemorrhagic shock and resuscitation. The final prognosis of I/R injury might be regulated by different genes, which is regarded as a complex network.}, } @article {pmid30384830, year = {2018}, author = {Gould, BA and Palacio-Mejia, JD and Jenkins, J and Mamidi, S and Barry, K and Schmutz, J and Juenger, TE and Lowry, DB}, title = {Population genomics and climate adaptation of a C4 perennial grass, Panicum hallii (Poaceae).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {792}, pmid = {30384830}, issn = {1471-2164}, support = {DE-SC0014156//U.S. Department of Energy/ ; IOS-0922457//Directorate for Biological Sciences/ ; IOS-0922457//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: Understanding how and why genetic variation is partitioned across geographic space is of fundamental importance to understanding the nature of biological species. How geographical isolation and local adaptation contribute to the formation of ecotypically differentiated groups of plants is just beginning to be understood through population genomic studies. We used whole genome sequencing combined with association study of climate to discover the drivers of differentiation in the perennial C4 grass Panicum hallii.

RESULTS: Sequencing of 89 natural accessions of P.hallii revealed complex population structure across the species range. Major population genomic separation was found between subspecies P.hallii var. hallii and var. filipes as well as between at least four major unrecognized subgroups within var. hallii. At least 139 genomic SNPs were significantly associated with temperature or precipitation across the range and these SNPs were enriched for non-synonymous substitutions. SNPs associated with temperature and aridity were more often found in or near genes than expected by chance and enriched for putative involvement in dormancy processes, seed maturation, response to hyperosmosis and salinity, abscisic acid metabolism, hormone metabolism, and drought recovery.

CONCLUSIONS: Both geography and climate adaptation contribute significantly to patterns of genome-wide variation in P.hallii. Population subgroups within P.hallii may represent early stages in the formation of ecotypes. Climate associated loci identified here represent promising targets for future research in this and other perennial grasses.}, } @article {pmid30383910, year = {2018}, author = {Guevara, EE and Lawler, RR}, title = {Epigenetic Clocks.}, journal = {Evolutionary anthropology}, volume = {27}, number = {6}, pages = {256-260}, doi = {10.1002/evan.21745}, pmid = {30383910}, issn = {1520-6505}, mesh = {Animals ; *Biological Clocks ; *Epigenesis, Genetic ; Humans ; Primates ; }, abstract = {Recent research has revealed clock-like patterns of epigenetic change across the life span in humans. Models describing these epigenetic changes have been dubbed "epigenetic clocks," and they can not only predict chronological age but also reveal biological age, which measures physiological homeostasis and deterioration over the life span. Comparative studies of the epigenetic clocks of different primate species are likely to provide insights into the evolution of life history schedules, as well as shed light on the physiological and genetic bases of aging and aging-related diseases. Chronological age estimation using clock-based calculators may also offer biological anthropologists a useful tool for applying to forensic and demographic studies.}, } @article {pmid30383523, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 8, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3394-3396}, doi = {10.1099/ijsem.0.002951}, pmid = {30383523}, issn = {1466-5034}, } @article {pmid30383522, year = {2018}, author = {Song, W and Duan, L and Zhao, J and Jiang, S and Guo, X and Xiang, W and Wang, X}, title = {Kribbella monticola sp. nov., a novel actinomycete isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3441-3446}, doi = {10.1099/ijsem.0.003007}, pmid = {30383522}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Genes, Bacterial ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinobacterium, designated strain NEAU-SW521T, was isolated from soil collected from Xianglu Mountain, Heilongjiang province, north PR China. The results of analysis of the 16S rRNA gene indicated that NEAU-SW521T represented a member of the genus Kribbella. The results of phylogenetic analyses using the 16S rRNA gene and multilocus sequence analysis using the concatenated gene sequences of the gyrB, rpoB, relA, recA and atpD genes all indicated that the strain formed a clade with Kribbella alba DSM 15500T (99.16 %), Kribbella ginsengisoli JCM 16928T (98.96 %), Kribbella catacumbae JCM 14968T (98.82 %), Kribbella sancticallisti JCM 14969T (98.62 %), Kribbella qitaiheensis NEAU-GQTH2-3T (98.61 %) and Kribbella koreensis JCM 10977T (98.47 %). The cell wall contained ll-diaminopimelic acid as the major diamino acid and the whole-cell hydrolysates were ribose, glucose and galactose. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid. The predominant menaquinone was MK-9(H4). Major fatty acids were iso-C16 : 0 and anteiso-C15 : 0. These chemotaxonomic data supported the affiliation of NEAU-SW521T to the genus Kribbella. The DNA G+C content was 67.8 mol%. Furthermore, the strain could be clearly distinguished by concatenated gene genetic distances, the combination of DNA-DNA hybridization results and some phenotypic characteristics. Therefore, it is proposed that NEAU-SW521T represents a novel species of the genus Kribbella, for which the name Kribbellamonticola sp. nov. is proposed. The type strain is NEAU-SW521T (=CGMCC 4.7465T=DSM 105770T).}, } @article {pmid30382927, year = {2018}, author = {Musuka, G and Teveredzi, V and Mutenherwa, F and Chingombe, I and Mapingure, M}, title = {Tuberculosis knowledge, misconceptions/myths in adults: findings from Lesotho, Malawi, Namibia and Zambia Demographic Health Surveys (2013-2016).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {778}, pmid = {30382927}, issn = {1756-0500}, abstract = {OBJECTIVE: To determine TB knowledge and misconceptions/myths amongst HIV positive and negative adults using Demographic Health Survey data from Lesotho, Malawi, Namibia and Zambia.

RESULTS: Overall 97% (n = 58,107) of both male and female respondents irrespective of their HIV status had heard of tuberculosis out of whom 82.6% knew that it can be cured. Knowledge that TB is spread in air when coughing or sneezing was 73.8%. Significantly higher proportions of HIV positive men and women than their HIV negative counterparts, had ever heard about TB, knew that it is transmitted through air when coughing and sneezing and also that it can be cured. However interestingly, significantly higher proportions of HIV positive men and women, than their HIV negative counterparts, had the misconception that TB is spread through sharing utensils or would overall say they did not know how it is spread. TB knowledge was significantly higher among individuals who are less than 26 years of age compared to those who were older.}, } @article {pmid30382925, year = {2018}, author = {Weinkove, D}, title = {On microbes, aging and the worm: an interview with David Weinkove.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {125}, pmid = {30382925}, issn = {1741-7007}, abstract = {David Weinkove is an associate professor at Durham University, UK, studying host-microbe interactions in the model organism Caenorhabditis elegans. David has been focusing on the way microbes affect the physiology of their hosts, including the process of aging. In this interview, he discusses the questions shaping his research, how they evolved over the years, and his guiding principles for leading a lab.}, } @article {pmid30382924, year = {2018}, author = {Monje, M}, title = {Open questions: why are babies rarely born with cancer?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {129}, pmid = {30382924}, issn = {1741-7007}, abstract = {Childhood cancer is fundamentally a disease of dysregulated development. Why does it rarely occur during the fetal period, a time of enormous growth and development?}, } @article {pmid30382918, year = {2018}, author = {Hurst, J}, title = {Communicating through scents: an interview with Jane Hurst.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {126}, pmid = {30382918}, issn = {1741-7007}, abstract = {Jane Hurst is a William Prescott Professor of Animal Science at the University of Liverpool, UK, studying scent communication in mammals and its role in behaviours. In this interview, Jane discusses how scents encode complex information in rodents, driving behaviours such as kinship interactions and choosing a mate, how understanding natural behaviours of animals can inform experimental designs, and what is the connection between Jane Austin and pheromones.}, } @article {pmid30382915, year = {2018}, author = {Dikic, I}, title = {Open questions: why should we care about ER-phagy and ER remodelling?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {131}, pmid = {30382915}, issn = {1741-7007}, abstract = {The endoplasmic reticulum (ER) is one of the most complex organelles in the eukaryotic cell. Recent findings suggest that a process called ER-phagy plays a major role in maintaining the ER's shape and function.}, } @article {pmid30382913, year = {2018}, author = {Khanal, L and Chalise, MK and Wan, T and Jiang, X}, title = {Riverine barrier effects on population genetic structure of the Hanuman langur (Semnopithecus entellus) in the Nepal Himalaya.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {159}, pmid = {30382913}, issn = {1471-2148}, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Colobinae/*genetics ; *Ecosystem ; Genetic Structures ; *Genetics, Population ; Geography ; Haplotypes/genetics ; Models, Theoretical ; Nepal ; Paleontology ; Phylogeny ; Polymorphism, Genetic ; *Rivers ; }, abstract = {BACKGROUND: Past climatological events and contemporary geophysical barriers shape the distribution, population genetic structure, and evolutionary history of many organisms. The Himalayan region, frequently referred to as the third pole of the Earth, has experienced large-scale climatic oscillations in the past and bears unique geographic, topographic, and climatic areas. The influences of the Pleistocene climatic fluctuations and present-day geographical barriers such as rivers in shaping the demographic history and population genetic structure of organisms in the Nepal Himalaya have not yet been documented. Hence, we examined the effects of late-Quaternary glacial-interglacial cycles and riverine barriers on the genetic composition of Hanuman langurs (Semnopithecus entellus), a colobine primate with a wide range of altitudinal distribution across the Nepalese Himalaya, using the mitochondrial DNA control region (CR, 1090 bp) and cytochrome B (CYTB, 1140 bp) sequences combined with paleodistribution modeling.

RESULTS: DNA sequences were successfully retrieved from 67 non-invasively collected fecal samples belonging to 18 wild Hanuman langur troops covering the entire distribution range of the species in Nepal. We identified 37 haplotypes from the concatenated CR + CYTB (2230 bp) sequences, with haplotype and nucleotide diversities of 0.958 ± 0.015 and 0.0237 ± 0.0008, respectively. The troops were clustered into six major clades corresponding to their river-isolated spatial distribution, with the significantly high genetic variation among these clades confirming the barrier effects of the snow-fed Himalayan rivers on genetic structuring. Analysis of demographic history projected a decrease in population size with the onset of the last glacial maximum (LGM); and, in accordance with the molecular analyses, paleodistribution modeling revealed a range shift in its suitable habitat downward/southward during the LGM. The complex genetic structure among the populations of central Nepal, and the stable optimal habitat through the last interglacial period to the present suggest that the central mid-hills of Nepal served as glacial refugia for the Hanuman langur.

CONCLUSIONS: Hanuman langurs of the Nepal Himalaya region exhibit high genetic diversity, with their population genetic structure is strongly shaped by riverine barrier effects beyond isolation by distance; hence, this species demands detailed future phylogenetic study.}, } @article {pmid30382907, year = {2018}, author = {Vernoux, T}, title = {Systems biology of meristems: an interview with Teva Vernoux.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {120}, doi = {10.1186/s12915-018-0591-7}, pmid = {30382907}, issn = {1741-7007}, abstract = {Teva Vernoux is a plant developmental biologist and holds positions as the Director of the Institute for Reproduction and Development of Plants at ENS de Lyon, and as a Research Director at Centre National de la Recherche Scientifique. Teva spoke to us about the need for multidisciplinary approaches to tackle multi-scale problems, how to go beyond a list of genes, and the importance of constructive reviews.}, } @article {pmid30382901, year = {2018}, author = {Hajissa, K and Muhajir, AEMA and Eshag, HA and Alfadel, A and Nahied, E and Dahab, R and Ali, SM and Mohammed, M and Gaafar, M and Mohamed, Z}, title = {Prevalence of schistosomiasis and associated risk factors among school children in Um-Asher Area, Khartoum, Sudan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {779}, pmid = {30382901}, issn = {1756-0500}, support = {SRIC/2017/RP761//Commission of Scientific Research and Innovation, Ministry of Higher Education and Scientific Research, Sudan/ ; }, abstract = {OBJECTIVE: Schistosomiasis remains one of the most common parasitic diseases worldwide. This is a cross-sectional study aimed to determine the prevalence of schistosomiasis and its associated risk factors among primary school children in Um-Asher area. The study was conducted among 170 primary school students in Um-Asher area from November 2017 to February 2018. Urine and stool samples were collected and examined for schistosomiasis infections. Moreover, data on sociodemographic characteristics and associated risk factors were obtained using a questionnaire.

RESULTS: The overall prevalence of Schistosoma haematobium was 12.9%, whereas that of Schistosoma mansoni was 2.95%. Additionally, the males had higher prevalence (60%) of S. mansoni than females (40%). However, both gender were equally infected with S. haematobium (50%). With regard to risk factors, distance of residence from water source and source of drinking water are relatively associated with the infection.}, } @article {pmid30382896, year = {2018}, author = {Calcino, AD and Fernandez-Valverde, SL and Taft, RJ and Degnan, BM}, title = {Diverse RNA interference strategies in early-branching metazoans.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {160}, pmid = {30382896}, issn = {1471-2148}, mesh = {Animals ; *Biological Evolution ; Ctenophora/genetics ; Drosophila/genetics ; Gene Library ; Genome ; MicroRNAs/genetics ; Molecular Sequence Annotation ; *RNA Interference ; RNA, Small Interfering/metabolism ; Sea Anemones/genetics ; }, abstract = {BACKGROUND: Micro RNAs (miRNAs) and piwi interacting RNAs (piRNAs), along with the more ancient eukaryotic endogenous small interfering RNAs (endo-siRNAs) constitute the principal components of the RNA interference (RNAi) repertoire of most animals. RNAi in non-bilaterians - sponges, ctenophores, placozoans and cnidarians - appears to be more diverse than that of bilaterians, and includes structurally variable miRNAs in sponges, an enormous number of piRNAs in cnidarians and the absence of miRNAs in ctenophores and placozoans.

RESULTS: Here we identify thousands of endo-siRNAs and piRNAs from the sponge Amphimedon queenslandica, the ctenophore Mnemiopsis leidyi and the cnidarian Nematostella vectensis using a computational approach that clusters mapped small RNA sequences and annotates each cluster based on the read length and relative abundance of the constituent reads. This approach was validated on 11 small RNA libraries in Drosophila melanogaster, demonstrating the successful annotation of RNAi-associated loci with properties consistent with previous reports. In the non-bilaterians we uncover seven new miRNAs from Amphimedon and four from Nematostella as well as sub-populations of candidate cis-natural antisense transcript (cis-NAT) endo-siRNAs. We confirmed the absence of miRNAs in Mnemiopsis but detected an abundance of endo-siRNAs in this ctenophore. Analysis of putative piRNA structure suggests that conserved localised secondary structures in primary transcripts may be important for the production of mature piRNAs in Amphimedon and Nematostella, as is also the case for endo-siRNAs.

CONCLUSION: Together, these findings suggest that the last common ancestor of extant animals did not have the entrained RNAi system that typifies bilaterians. Instead it appears that bilaterians, cnidarians, ctenophores and sponges express unique repertoires and combinations of miRNAs, piRNAs and endo-siRNAs.}, } @article {pmid30382892, year = {2018}, author = {Krasileva, K}, title = {From plant immunity to food security: an interview with Ksenia Krasileva.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {123}, pmid = {30382892}, issn = {1741-7007}, abstract = {Ksenia Krasileva is an Assistant Professor at UC Berkley, studying innate immunity in plants. Ksenia's work combines plant genomics and plant-microbe interactions with new technologies, spanning basic studies and translational research in agriculture. In this interview Ksenia shares her experience with research and leading a lab, as well as thoughts on innovations in publishing.}, } @article {pmid30382890, year = {2018}, author = {Nguyen, LT and Guo, M and Naugler, C and Rashid-Kolvear, F}, title = {Incidence of chronic myeloid leukemia in Calgary, Alberta, Canada.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {780}, pmid = {30382890}, issn = {1756-0500}, support = {RN254781-333204//Canadian Institutes of Health Research/Canada ; }, abstract = {OBJECTIVE: The epidemiology of chronic myeloid leukemia is shifting due to the aging global population and the recent discovery and availability of targeted treatment options. This study provides recent data regarding the incidence of CML in Calgary, a major Canadian city. Data from patients diagnosed with CML by bone marrow sample analysis from 2011 to 2015 were collected from the database of the sole centralized cytogenetics facility in service of Calgary and its surrounding area.

RESULTS: With an average of 10.2 newly diagnosed cases per year in Calgary from 2011 to 2015, the incidence rate was calculated to be 0.75 cases per 100,000 person-years (95% CI 0.57-0.99). With age standardization, the incidence was 0.87 cases per 100,000 person-years (95% CI 0.82-0.91) for the Canadian population, which was low compared to other developed Western nations. The highest incidence rates were observed in the older patient categories, however there was a broad age distribution for incident cases and the median age at diagnosis was 48. There was a general male bias for CML most pronounced at the younger ages. Our description of CML incidence will help to inform healthcare planners amidst the dramatically altered treatment of this hematological neoplasm.}, } @article {pmid30382888, year = {2018}, author = {Shiferaw, MB and Yismaw, G and Getachew, H}, title = {Specimen rejections among referred specimens through referral network to the Amhara Public Health Institute for laboratory testing, Bahir Dar, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {781}, pmid = {30382888}, issn = {1756-0500}, abstract = {OBJECTIVE: The aim of this study was to assess the magnitude, trend and reasons of rejection among referred specimens through referral network to the Amhara Public Health Institute (APHI) for laboratory testing.

RESULTS: A total of 42,923 specimens were received at APHI reference laboratories. Of which, 221 (0.5%) specimens were rejected. CD4, HIV viral load, genexpert and EID specimens' rejection rates were 0.7%, 0.6%, 0.3% and 0.2%, respectively. CD4 specimens were rejected due to wrong package (84.2%) and presence of clots (15.8%). Un-centrifuge (46.9%), hemolysis (19.8%) and use of wrong tube (17.7%) were the main rejection reasons for HIV viral load specimens. Although viral load specimen rejection was improved from 1.8 to 0% up to February/2018, the problem was reoccurred and continued to the end of May (1.3%) and June (0.3%) 2018. Moreover, CD4 specimen rejection (4.3%) was out of the established target in May, and exposed infant diagnosis (EID) specimen rejection became increased since March 2018. Hence, appropriate corrective and preventive actions and close follow up could reduce the problem of specimen referral network.}, } @article {pmid30382879, year = {2018}, author = {Waqas, A and Naveed, S and Aedma, KK and Tariq, M and Afzaal, T}, title = {Exploring clusters of defense styles, psychiatric symptoms and academic achievements among medical students: a cross-sectional study in Pakistan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {782}, pmid = {30382879}, issn = {1756-0500}, abstract = {OBJECTIVE: The clusters of participants with a homogeneous psychological make-up can be identified using sophisticated machine learning techniques such as the two-step clustering algorithm. It can also help us to identify the synergistic and additive effects of a range of psychometric variables. The identification of synergistic effect of this clustering of defense mechanism has significant practical implications as they share a certain variance. This study aims to identify the clusters of ego defenses and their relationship with academic performance and mental health outcome in medical students.

RESULTS: The high achievers scored higher on mature and neurotic defense styles and lower on immature than their counter parts. A higher proportion of medical students in high achievers group had normal scores on depressive symptoms than low achievers. While a majority among low achievers suffered from severe anxiety levels than high achievers group. High achievers scored higher on sublimation, humor, anticipation, suppression, pseudo-altruism, idealization, reaction formation, autistic fantasy, denial, and rationalization.}, } @article {pmid30382878, year = {2018}, author = {Walker, AW}, title = {Studying the microbiome and its complexities: an interview with Alan Walker.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {134}, pmid = {30382878}, issn = {1741-7007}, abstract = {Alan Walker is a Senior Lecturer at the University of Aberdeen, UK, studying the intestinal microbiota and its interactions with the host's diet. In this interview, Alan discusses his research interests, earlier studies of the ways contaminants can affect microbiome analyses, the excitement of experiments going well, and why science doesn't need to be combative.}, } @article {pmid30382870, year = {2018}, author = {Dacks, JB}, title = {Evolving eukaryotes: an interview with Joel Dacks.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {119}, pmid = {30382870}, issn = {1741-7007}, support = {R21 ES021028/ES/NIEHS NIH HHS/United States ; }, abstract = {Joel Dacks is an Associate Professor and Canada Research Chair in Evolutionary Cell Biology at the University of Alberta, a Scientific Associate at the Natural History Museum (London), and the current President of the International Society for Evolutionary Protistology. His research group studies the evolution and diversity of the eukaryotic membrane-trafficking system, from origins to potential disease therapeutics. In this interview, Joel shares some perspectives on gaining a balanced view of comparative cell biology and the importance of a constructive peer review process.}, } @article {pmid30382858, year = {2018}, author = {Stollewerk, A}, title = {Evolutionary development and morphological modifications of the brain: an interview with Angelika Stollewerk.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {117}, pmid = {30382858}, issn = {1741-7007}, abstract = {Angelika Stollewerk is a Reader at Queen Mary University of London, where her lab uses a diverse range of species to study the evolution of the arthropod nervous system. Angelika spoke to us about social spiders, the future of evo-devo, and open peer review.}, } @article {pmid30382848, year = {2018}, author = {Song, GQ and Walworth, A}, title = {An invaluable transgenic blueberry for studying chilling-induced flowering in woody plants.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {265}, pmid = {30382848}, issn = {1471-2229}, mesh = {Blueberry Plants/*genetics ; Cold Temperature ; Flowers/genetics/*physiology ; *Gene Expression Regulation, Plant ; Genome, Plant ; Mutation ; Phenotype ; *Plants, Genetically Modified ; Transgenes ; }, abstract = {BACKGROUND: Many deciduous woody crops require a minimum level of chilling to break dormancy and allow the seasonal growth of vegetative and floral buds. In this study, we report the discovery of an invaluable transgenic event of the blueberry cultivar 'Legacy' (hereafter, Mu-Legacy) for studying chilling-induced flowering in woody plants. Mu-legacy and its progeny provide a unique material to study the unknown mechanism of chilling-mediated flowering in woody plants.

RESULTS: Unlike nontransgenic 'Legacy' and plants of 48 other transgenic events, Mu-Legacy plants were able to flower under nonchilling conditions and had early flower bud formation, reduced plant size, and reduced chilling requirement for normal flowering. These characteristics were heritable and also observed in self-pollinated, transgenic T1 progenies of Mu-Legacy. A 47-Kbp genomic sequence surrounding the transgene insertion position was identified. RNA-sequencing data showed increased expression of a RESPONSE REGULATOR 2-like gene (VcRR2), located adjacent to the insertion position in Mu-Legacy and likely driven by the CaMV 35S promoter of the transgene. The Mu-Legacy showed 209 differentially expressed genes (DEGs) in nonchilled flower buds (compared to nontransgenic 'Legacy'), of which only four DEGs were in the flowering pathway. This suggests altered expression of these few genes, VcRR2 and four flowering DEGs, is sufficient to significantly change flowering behavior in Mu-Legacy.

CONCLUSIONS: The significance of VcRR2 in Mu-Legacy suggests that the VcRR2-involved cytokinin pathway likely contributes to the major differences in chilling-mediated flowering between woody and herbaceous plants. More importantly, Mu-Legacy shows increased yield potential, a decreased chilling requirement, and better winter hardiness than many low-chilling cultivars growing in southern warm winter conditions.}, } @article {pmid30382847, year = {2018}, author = {Couvreur, TLP}, title = {Unraveling rain forest biodiversity: an interview with Thomas Couvreur.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {127}, pmid = {30382847}, issn = {1741-7007}, abstract = {Thomas Couvreur is a researcher and botanist at the Institut de Recherche pour le Développement (IRD), based in Montpellier, France, studying tropical biosystems. He is using diverse approaches-from taxonomy, molecular phylogenetics, phylogeography, to modeling species distribution-to understand the evolution and resilience of biodiversity in rain forests. In this interview, Thomas describes the ongoing research in his lab, the most urgent challenges and opportunities in biodiversity research, and the importance of knowing how to code.}, } @article {pmid30382846, year = {2018}, author = {Ebert, D}, title = {Open questions: what are the genes underlying antagonistic coevolution?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {114}, pmid = {30382846}, issn = {1741-7007}, abstract = {Although the idea of coevolution was first presented 150 years ago, we still only vaguely understand the genetic basis of its workings. Identifying the genes responsible for coevolutionary interactions would enable us to distinguish between fundamentally different models of coevolution and would represent a milestone in population genetics and genomics.}, } @article {pmid30382844, year = {2018}, author = {Huang, KC}, title = {When a physicist wanders into biology…: an interview with KC Huang.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {130}, pmid = {30382844}, issn = {1741-7007}, abstract = {Kerwyn Casey ("KC") Huang is an Associate Professor at Stanford University, studying the physical nature of biological systems and the underpinnings of fundamental processes such as cell shape determination, cell division, and intracellular and microbial community organization. In this interview, KC discusses how the ability to pursue insights at scales from molecules to cellular communities can shed new light on longstanding questions, the necessity for new tools in exploring the microbiome, how to create an empowering lab environment, and why integrating chemistry with physics and biology can bring us closer to asking the right questions.}, } @article {pmid30382842, year = {2018}, author = {Zeller, MA and Anderson, TK and Walia, RW and Vincent, AL and Gauger, PC}, title = {ISU FLUture: a veterinary diagnostic laboratory web-based platform to monitor the temporal genetic patterns of Influenza A virus in swine.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {397}, pmid = {30382842}, issn = {1471-2105}, support = {721-18-17-IR-1710//Iowa State University (US) Presidential Interdisciplinary Research Initiative/ ; NA//USDA-ARS/ ; HHSN272201400008C/AI/NIAID NIH HHS/United States ; HHSN272201400008C//Center of Excellence in Influenza Research and Surveillance CEIRS/ ; DE-AC05-060R23100//Oak Ridge Institute for Science and Education/ ; }, mesh = {Animals ; Influenza A virus/*classification/genetics/isolation & purification ; *Internet ; Laboratories/*standards ; Molecular Diagnostic Techniques/*methods ; Orthomyxoviridae Infections/epidemiology/*veterinary/virology ; Phylogeny ; Swine ; Swine Diseases/*diagnosis/epidemiology/*virology ; United States/epidemiology ; }, abstract = {BACKGROUND: Influenza A Virus (IAV) causes respiratory disease in swine and is a zoonotic pathogen. Uncontrolled IAV in swine herds not only affects animal health, it also impacts production through increased costs associated with treatment and prevention efforts. The Iowa State University Veterinary Diagnostic Laboratory (ISU VDL) diagnoses influenza respiratory disease in swine and provides epidemiological analyses on samples submitted by veterinarians.

DESCRIPTION: To assess the incidence of IAV in swine and inform stakeholders, the ISU FLUture website was developed as an interactive visualization tool that allows the exploration of the ISU VDL swine IAV aggregate data in the clinical diagnostic database. The information associated with diagnostic cases has varying levels of completeness and is anonymous, but minimally contains: sample collection date, specimen type, and IAV subtype. Many IAV positive samples are sequenced, and in these cases, the hemagglutinin (HA) sequence and genetic classification are completed. These data are collected and presented on ISU FLUture in near real-time, and more than 6,000 IAV positive diagnostic cases and their epidemiological and evolutionary information since 2003 are presented to date. The database and web interface provides rapid and unique insight into the trends of IAV derived from both large- and small-scale swine farms across the United States of America.

CONCLUSION: ISU FLUture provides a suite of web-based tools to allow stakeholders to search for trends and correlations in IAV case metadata in swine from the ISU VDL. Since the database infrastructure is updated in near real-time and is integrated within a high-volume veterinary diagnostic laboratory, earlier detection is now possible for emerging IAV in swine that subsequently cause vaccination and control challenges. The access to real-time swine IAV data provides a link with the national USDA swine IAV surveillance system and allows veterinarians to make objective decisions regarding the management and control of IAV in swine. The website is publicly accessible at http://influenza.cvm.iastate.edu .}, } @article {pmid30382841, year = {2018}, author = {Tan, T and Xia, L and Tu, K and Tang, J and Yin, S and Dai, L and Lei, P and Dong, B and Hu, H and Fan, Y and Yu, Y and Xie, D}, title = {Improved Macaca fascicularis gene annotation reveals evolution of gene expression profiles in multiple tissues.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {787}, pmid = {30382841}, issn = {1471-2164}, support = {91631111//National Natural Science Foundation of China/ ; 31571327//National Natural Science Foundation of China/ ; 31771426//National Natural Science Foundation of China/ ; 91740111//National Natural Science Foundation of China/ ; 81570060//National Natural Science Foundation of China/ ; 2016YFA0502203//the National Key Research and Development Program/ ; 2017YFC0840100//the National Key Research and Development Program/ ; }, abstract = {BACKGROUNDS: Macaca fascicularis (M. fascicularis) is a primate model organism that played important role in studying human health. It is vital to better understand the similarity and differences of gene regulation between M. fascicularis and human. Current comparative study of gene regulation between the two species are limited by low quality of gene annotation and lack of regulatory element data on M. fascicularis genome.

RESULTS: In this study, we improved the M. fascicularis gene annotation with 57 gene expression data from multiple tissues and, more importantly, a manual curation procedure. The new annotation enabled us to map gene expression and identify gene location more accurately.

CONCLUSIONS: Comparing with human gene expression data from the same cell types, we characterized the evolution of expression patterns of homologous genes.}, } @article {pmid30382840, year = {2018}, author = {Vu, TN and Deng, W and Trac, QT and Calza, S and Hwang, W and Pawitan, Y}, title = {A fast detection of fusion genes from paired-end RNA-seq data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {786}, pmid = {30382840}, issn = {1471-2164}, abstract = {BACKGROUND: Fusion genes are known to be drivers of many common cancers, so they are potential markers for diagnosis, prognosis or therapy response. The advent of paired-end RNA sequencing enhances our ability to discover fusion genes. While there are available methods, routine analyses of large number of samples are still limited due to high computational demands.

RESULTS: We develop FuSeq, a fast and accurate method to discover fusion genes based on quasi-mapping to quickly map the reads, extract initial candidates from split reads and fusion equivalence classes of mapped reads, and finally apply multiple filters and statistical tests to get the final candidates. We apply FuSeq to four validated datasets: breast cancer, melanoma and glioma datasets, and one spike-in dataset. The results reveal high sensitivity and specificity in all datasets, and compare well against other methods such as FusionMap, TRUP, TopHat-Fusion, SOAPfuse and JAFFA. In terms of computational time, FuSeq is two-fold faster than FusionMap and orders of magnitude faster than the other methods.

CONCLUSIONS: With this advantage of less computational demands, FuSeq makes it practical to investigate fusion genes in large numbers of samples. FuSeq is implemented in C++ and R, and available at https://github.com/nghiavtr/FuSeq for non-commercial uses.}, } @article {pmid30382839, year = {2018}, author = {Troemel, E}, title = {Host-parasite interactions: an interview with Emily Troemel.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {133}, pmid = {30382839}, issn = {1741-7007}, support = {R01 AG052622/AG/NIA NIH HHS/United States ; R01 GM114139/GM/NIGMS NIH HHS/United States ; R56 AG052622/AG/NIA NIH HHS/United States ; }, abstract = {Emily Troemel is a Professor at the University of California San Diego, where her lab uses Caenorhabditis elegans to study host-pathogen interactions and the shaping of the immune response. In this interview, Emily shared her thoughts on peer review and its role in training future scientists, and the possibility of a new form of immunity in epithelia.}, } @article {pmid30382838, year = {2018}, author = {Terauchi, R}, title = {Dissecting the forces that shape crops: an interview with Ryohei Terauchi.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {132}, pmid = {30382838}, issn = {1741-7007}, abstract = {Ryohei Terauchi is a Professor at Kyoto University and a Group Leader at the Iwate Biotechnology Research Center, Japan, studying the evolution of crops and their pathogens. In this interview, Ryohei describes his research interests, how the revolution in sequencing technology helped improve our understanding of orphan crops, and who are the scientists that inspire him.}, } @article {pmid30382837, year = {2018}, author = {Ferrier, DEK}, title = {Horizons in evolutionary genomics: an interview with David Ferrier.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {124}, pmid = {30382837}, issn = {1741-7007}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {David Ferrier is a Reader at the University of St Andrews and Deputy Director of the Scottish Oceans Institute, where his lab studies how the diversity of form in the animal kingdom evolved, with an emphasis on using comparative genomics. In this interview, David shares his thoughts on how to escape the 'straitjacket' of traditional model systems, transparency in peer review, and the past and future of genome sequencing.}, } @article {pmid30382836, year = {2018}, author = {Hirst, J}, title = {Open questions: respiratory chain supercomplexes-why are they there and what do they do?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {111}, pmid = {30382836}, issn = {1741-7007}, support = {MC_U105663141//Medical Research Council/United Kingdom ; MC_UU_00015/2//Medical Research Council/United Kingdom ; }, abstract = {In the mitochondrial inner membrane the respiratory enzymes associate to form supramolecular assemblies known as supercomplexes. The existence of supercomplexes is now widely accepted-but what functional or structural advantages, if any, do they confer?}, } @article {pmid30382834, year = {2018}, author = {Hanage, WP}, title = {From bacterial genomics to clinical epidemiology: an interview with Bill Hanage.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {122}, pmid = {30382834}, issn = {1741-7007}, abstract = {Bill Hanage is an Associate Professor of Epidemiology at Harvard School of Public Health, where he studies fundamental and applied epidemiology using genomic and evolutionary methods. Bill spoke to us about the different types of selection that determine pathogen populations, asking reviewers to highlight positives of papers, and whether we're closer to a causal framework for studying the microbiome.}, } @article {pmid30382833, year = {2018}, author = {Burgess, HA}, title = {Startling responses of zebrafish: an interview with Harold Burgess.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {118}, doi = {10.1186/s12915-018-0589-1}, pmid = {30382833}, issn = {1741-7007}, abstract = {Harold Burgess is a Senior Investigator at the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health. Work in his lab combines genetic and imaging techniques to study neural circuits required for sensory guided behavior in zebrafish. In this interview Harold shares his thoughts on the changing field of neural development, pre-publication review, and 'Darwinian experiments' of peer review.}, } @article {pmid30382832, year = {2018}, author = {Pereira, GS and Garcia, AAF and Margarido, GRA}, title = {A fully automated pipeline for quantitative genotype calling from next generation sequencing data in autopolyploids.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {398}, pmid = {30382832}, issn = {1471-2105}, support = {#2012/25236-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; #2015/22993-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 312448/2013-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; #2008/52197-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Automation, Laboratory ; Genetic Markers ; Genotype ; Genotyping Techniques/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Medicago sativa/*genetics ; *Polymorphism, Single Nucleotide ; *Polyploidy ; *Software ; Solanum tuberosum/*genetics ; }, abstract = {BACKGROUND: Genotyping-by-sequencing (GBS) has been used broadly in genetic studies for several species, especially those with agricultural importance. However, its use is still limited in autopolyploid species because genotype calling software generally fails to properly distinguish heterozygous classes based on allele dosage.

RESULTS: VCF2SM is a Python script that integrates sequencing depth information of polymorphisms in variant call format (VCF) files and SUPERMASSA software for quantitative genotype calling. VCFs can be obtained from any variant discovery software that outputs exact allele sequencing depth, such as a modified version of the TASSEL-GBS pipeline provided here. VCF2SM was successfully applied in analyzing GBS data from diverse panels (alfalfa and potato) and full-sib mapping populations (alfalfa and switchgrass) of polyploid species.

CONCLUSIONS: We demonstrate that our approach can help plant geneticists working with autopolyploid species to advance their studies by distinguishing allele dosage from GBS data.}, } @article {pmid30382831, year = {2018}, author = {Min, B and Kim, S and Oh, YL and Kong, WS and Park, H and Cho, H and Jang, KY and Kim, JG and Choi, IG}, title = {Genomic discovery of the hypsin gene and biosynthetic pathways for terpenoids in Hypsizygus marmoreus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {789}, pmid = {30382831}, issn = {1471-2164}, abstract = {BACKGROUND: Hypsizygus marmoreus (Beech mushroom) is a popular ingredient in Asian cuisine. The medicinal effects of its bioactive compounds such as hypsin and hypsiziprenol have been reported, but the genetic basis or biosynthesis of these components is unknown.

RESULTS: In this study, we sequenced a reference strain of H. marmoreus (Haemi 51,987-8). We evaluated various assembly strategies, and as a result the Allpaths and PBJelly produced the best assembly. The resulting genome was 42.7 Mbp in length and annotated with 16,627 gene models. A putative gene (Hypma_04324) encoding the antifungal and antiproliferative hypsin protein with 75% sequence identity with the previously known N-terminal sequence was identified. Carbohydrate active enzyme analysis displayed the typical feature of white-rot fungi where auxiliary activity and carbohydrate-binding modules were enriched. The genome annotation revealed four terpene synthase genes responsible for terpenoid biosynthesis. From the gene tree analysis, we identified that terpene synthase genes can be classified into six clades. Four terpene synthase genes of H. marmoreus belonged to four different groups that implies they may be involved in the synthesis of different structures of terpenes. A terpene synthase gene cluster was well-conserved in Agaricomycetes genomes, which contained known biosynthesis and regulatory genes.

CONCLUSIONS: Genome sequence analysis of this mushroom led to the discovery of the hypsin gene. Comparative genome analysis revealed the conserved gene cluster for terpenoid biosynthesis in the genome. These discoveries will further our understanding of the biosynthesis of medicinal bioactive molecules in this edible mushroom.}, } @article {pmid30382829, year = {2018}, author = {Kawamura, E and Hamilton, GB and Miskiewicz, EI and MacPhee, DJ}, title = {Fermitin family homolog-2 (FERMT2) is highly expressed in human placental villi and modulates trophoblast invasion.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {19}, pmid = {30382829}, issn = {1471-213X}, support = {101051//Canadian Institutes of Health Research/Canada ; 2776//Saskatchewan Health Research Foundation/ ; 32512//Canada Foundation for Innovation/ ; 417785//Western College of Veterinary Medicine Research Trust/ ; }, abstract = {BACKGROUND: Integrins are transmembrane receptors that mediate cell-extracellular matrix (ECM) and cell-cell adhesion and trophoblast cells undergo changes in integrin expression as they differentiate. However, the mechanism(s) of integrin activation leading to integrin-mediated signaling in trophoblast cell differentiation is unknown. The Fermitin family proteins are integrin activators that help mediate integrin-mediated signaling, but have never been studied in detail within the human placenta. Thus, we examined the spatiotemporal pattern of expression of Fermitin family homolog-2 (FERMT2) in human chorionic villi throughout gestation and its role in trophoblast-substrate adhesion and invasion.

METHODS: Placental villous tissue was obtained from patients undergoing elective terminations by dilatation and curettage at weeks 8-12 (n = 10), weeks 13-14 (n = 8), as well as from term deliveries at weeks 37-40 (n = 6). Tissues were fixed, processed and sections utilized for immunofluorescence analysis of FERMT2 expression during gestation. Additionally, HTR8-SVneo human trophoblast cells were transfected by electroporation with FERMT2-specific siRNAs or non-targeting siRNAs (control) and used in cell-substrate adhesion as well as invasion assays.

RESULTS: FERMT2 was more commonly expressed in the basal domain of villous cytotrophoblast cells and prominently localized around the periphery of individual extravillous trophoblast cells. siRNA-mediated knockdown of FERMT2 in HTR8-SVneo cells resulted in significantly decreased trophoblast-substrate attachment (p < 0.05) as well as significantly decreased trophoblast invasion (p < 0.05) relative to control cells.

CONCLUSIONS: The detection of FERMT2 throughout extravillous trophoblast columns and the results of invasion assays demonstrated that this protein is likely an important regulator of integrin activation in extravillous cells to modulate migration and invasion.}, } @article {pmid30382825, year = {2018}, author = {Yang, Y and Xuan, L and Yu, C and Wang, Z and Xu, J and Fan, W and Guo, J and Yin, Y}, title = {High-density genetic map construction and quantitative trait loci identification for growth traits in (Taxodium distichum var. distichum × T. mucronatum) × T. mucronatum.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {263}, doi = {10.1186/s12870-018-1493-0}, pmid = {30382825}, issn = {1471-2229}, support = {31700588//National Youth Foundation of China/ ; BK20160601//Natural Science Foundation of Jiangsu Province/ ; BK20150551//Natural Science Foundation of Jiangsu Province/ ; CX(16)1005//Jiangsu Agriculture Science and Technology Innovation Fund/ ; }, mesh = {Crosses, Genetic ; Genetic Markers ; Genome, Plant ; *Quantitative Trait Loci ; Seedlings/genetics ; Taxodium/*genetics/*growth & development ; }, abstract = {BACKGROUND: 'Zhongshanshan' is the general designation for the superior interspecific hybrid clones of Taxodium species, which is widely grown for economic and ecological purposes in southern China. Growth is the priority objective in 'Zhongshanshan' tree improvement. A high-density linkage map is vital to efficiently identify key quantitative trait loci (QTLs) that affect growth.

RESULTS: In total, 403.16 Gb of data, containing 2016,336 paired-end reads, was obtained after preprocessing. The average sequencing depth was 28.49 in T. distichum var. distichum, 25.18 in T. mucronatum, and 11.12 in each progeny. In total, 524,662 high-quality SLAFs were detected, of which 249,619 were polymorphic, and 6166 of the polymorphic markers met the requirements for use in constructing a genetic map. The final map harbored 6156 SLAF markers on 11 linkage groups, and was 1137.86 cM in length, with an average distance of 0.18 cM between adjacent markers. Separate QTL analyses of traits in different years by CIM detected 7 QTLs. While combining multiple-year data, 13 QTLs were detected by ICIM. 5 QTLs were repeatedly detected by the two methods, and among them, 3 significant QTLs (q6-2, q4-2 and q2-1) were detected in at least two traits. Bioinformatic analysis discoveried a gene annotated as a leucine-rich repeat receptor-like kinase gene within q4-2.

CONCLUSIONS: This map is the most saturated one constructed in a Taxodiaceae species to date, and would provide useful information for future comparative mapping, genome assembly, and marker-assisted selection.}, } @article {pmid30382823, year = {2018}, author = {Steuer, P and Avilez, C and Tejeda, C and Gonzalez, N and Ramirez-Reveco, A and Ulloa, F and Mella, A and Grant, IR and Collins, MT and Salgado, M}, title = {In vitro inactivation of Mycobacterium avium subsp. paratuberculosis (MAP) by use of copper ions.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {172}, pmid = {30382823}, issn = {1471-2180}, support = {1161633//FONDECYT/ ; beca doctorado nacional//CONICYT/ ; }, abstract = {BACKGROUND: Mycobacterium avium subsp. paratuberculosis (MAP) is the causative agent of paratuberculosis, a contagious infectious disease that affects domestic and wild ruminants causing chronic inflammation of the intestine. MAP has proven to be very resistant to both physical and chemical processes, making it difficult to control this pathogen. Based on the recognized antimicrobial properties of copper, the objective of this study was to evaluate the effectiveness of copper ions to reduce MAP numbers and/or MAP viability in a fluid matrix. Besides, methicillin-resistant Staphylococcus aureus (MRSA), and Escherichia coli were used as controls of the effectiveness of copper ions. MAP-spiked PBS was subjected to copper ions treatment at 24 V for 5 min and the PBS suspensions were sampled before and after treatment. MAP viability and quantification were determined using three complementary techniques: a phage amplification assay, MGIT culture and qPCR.

RESULTS: Moderate numbers (103 CFU ml-1) of the two control bacteria were completely eliminated by treatment with copper ions. For MAP, copper ions treatment reduced both the viability and numbers of this pathogen. Phage assay information quickly showed that copper ions (24 V for 5 min) resulted in a significant reduction in viable MAP. MGIT culture results over time showed statistically significant differences in time-to-detection (TTD) values between PRE and POST treatment. MAP genome equivalent estimates for PBS suspensions indicated that MAP numbers were lower in samples POST-treatment with copper ions than PRE-treatment.

CONCLUSIONS: The use of copper ions resulted in a significant reduction of MAP in a liquid matrix, although some MAP survival on some occasions was observed.}, } @article {pmid30382818, year = {2018}, author = {Dubois, B and Bertin, P and Hautier, L and Muhovski, Y and Escarnot, E and Mingeot, D}, title = {Genetic and environmental factors affecting the expression of α-gliadin canonical epitopes involved in celiac disease in a wide collection of spelt (Triticum aestivum ssp. spelta) cultivars and landraces.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {262}, pmid = {30382818}, issn = {1471-2229}, mesh = {Celiac Disease/etiology/immunology ; Epitopes/*genetics ; Fertilizers ; Gene Expression Regulation, Plant ; Gliadin/genetics/*immunology ; Humans ; Nitrogen/metabolism ; Polymerase Chain Reaction/methods ; Triticum/*genetics/immunology ; }, abstract = {BACKGROUND: Celiac disease (CD) is an autoimmune disorder affecting genetically predisposed individuals whose dietary gluten proteins trigger an inflammatory reaction in the small intestine. Gluten is found in the seeds of cereals like bread wheat (Triticum aestivum ssp. aestivum) and spelt (Triticum aestivum ssp. spelta). The development of new varieties lacking immunogenic peptides is one of the strategies currently investigated to address the CD problem. Among gluten proteins, α-gliadins display the strongest immunogenicity with four main T-cell stimulatory epitopes. The objective of this work was to study the expression of α-gliadin epitopes related to CD in a wide collection of 121 spelt accessions (landraces and varieties, spring and winter accessions) from different provenances, and to analyze the correlation between the presence of epitope sequences in gDNA and their expression (cDNA). The effect of environmental factors (harvest year and N fertilization) on the epitope expression was also investigated.

RESULTS: TaqMan probes targeting the canonical form of the epitopes were used to evaluate the epitope expression levels. Significant variations in the amount of epitope transcripts were identified between accessions and according to the provenances. Spring accessions showed a significantly higher immunogenicity than winter ones and no influence of spelt breeding on the epitope expression levels could be assessed when comparing landraces and varieties from Northwestern Europe. No correlation was observed between quantitative PCR results obtained from cDNA and gDNA for 45 accessions tested, stressing the need to use markers focusing on epitope transcripts rather than on genomic sequences. A relative stability of the amount of epitopes expressed by a same accession across four harvest years was detected. The fertilization strategy, evaluated through seven N fertilization modalities applied to two commercial spelt varieties, did not influence the epitope expression of the first variety, whereas it had a slight effect for the second one.

CONCLUSIONS: The results obtained in this work showed that the CD-related epitope expression greatly fluctuated among the spelt accessions studied. This expression was not correlated to the epitope genomic occurrence and environmental factors had almost no influence on the amount of epitope transcripts.}, } @article {pmid30382816, year = {2018}, author = {Xu, X and Chen, Z and Shi, YF and Wang, HM and He, Y and Shi, L and Chen, T and Wu, JL and Zhang, XB}, title = {Functional inactivation of OsGCNT induces enhanced disease resistance to Xanthomonas oryzae pv. oryzae in rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {264}, pmid = {30382816}, issn = {1471-2229}, support = {31471572//National Natural Science Foundation of China/ ; 2016YFD0101104//Ministry of Science and Technology of the People's Republic of China/ ; }, mesh = {Cell Death/genetics ; Cloning, Molecular ; Cyclopentanes/metabolism ; Disease Resistance/genetics ; Gene Expression Regulation, Plant ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/genetics ; Mutation ; Oryza/*genetics/*microbiology ; Oxylipins/metabolism ; Phylogeny ; Plant Diseases/*microbiology ; Plant Immunity ; Plant Leaves/cytology/genetics/microbiology ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; Xanthomonas/*pathogenicity ; }, abstract = {BACKGROUND: Spotted-leaf mutants are important to reveal programmed cell death and defense-related pathways in rice. We previously characterized the phenotype performance of a rice spotted-leaf mutant spl21 and narrowed down the causal gene locus spl21(t) to an 87-kb region in chromosome 12 by map-based cloning.

RESULT: We showed that a single base substitution from A to G at position 836 in the coding sequence of Oryza sativa beta-1,6-N-acetylglucosaminyl transferase (OsGCNT), effectively mutating Tyr to Cys at position 279 in the translated protein sequence, was responsible for the spotted-leaf phenotype as it could be rescued by functional complementation. Compared to the wild type IR64, the spotted-leaf mutant spl21 exhibited loss of chlorophyll, breakdown of chloroplasts, down-regulation of photosynthesis-related genes, and up-regulation of senescence associated genes, which indicated that OsGCNT regulates premature leaf senescence. Moreover, the enhanced resistance to the bacterial leaf blight pathogen Xanthomonas oryzae pv. oryzae, up-regulation of pathogenesis-related genes and increased level of jasmonate which suggested that OsGCNT is a negative regulator of defense response in rice. OsGCNT was expressed constitutively in the leaves, sheaths, stems, roots, and panicles, and OsGCNT-GFP was localized to the Golgi apparatus. High throughput RNA sequencing analysis provided further evidence for the biological effects of loss of OsGCNT function on cell death, premature leaf senescence and enhanced disease resistance in rice. Thus, we demonstrated that the novel OsGCNT regulated rice innate immunity and immunity-associated leaf senescence probably by changing the jasmonate metabolic pathway.

CONCLUSIONS: These results reveal that a novel gene Oryza sativa beta-1,6-N-acetylglucosaminyl transferase (OsGCNT) is responsible for the spotted-leaf mutant spl21, and OsGCNT acts as a negative-regulator mediating defense response and immunity-associated premature leaf senescence probably by activating jasmonate signaling pathway.}, } @article {pmid30382814, year = {2018}, author = {Gui, LS and Raza, SHA and Garcia, M and Sun, YG and Ullah, I and Han, YC}, title = {Genetic variants in the SIRT6 transcriptional regulatory region affect gene activity and carcass quality traits in indigenous Chinese beef cattle (Bos taurus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {785}, pmid = {30382814}, issn = {1471-2164}, support = {(2014-NK-A6-2)//key scientific research programs of Qinghai province/ ; }, abstract = {BACKGROUND: The aim of this study was to analyze potential influences of polymorphisms within the regulatory region of the bovine SIRT6 gene on carcass quality traits. Expression analyses suggested that SIRT6 gene is predominately expressed in kidney, compared with other tissues. In 535 indigenous Chinese beef cattle, two novel single nucleotide polymorphisms (SNPs) were identified within the promoter region of the SIRT6 gene.

RESULTS: Association analysis indicated that G allele of the c.-1100 A > G had a positive effect on fat deposition, and the Hap4/4 diplotype had more favourable results than other dipoltypes with respect to the evaluation of carcass quality traits. Furthermore, promoter activity associated with the Hap3 haplotype was measured at higher levels than the Hap1 haplotype, which would be in agreement with the previously described association analysis.

CONCLUSION: The SIRT6 promoter variants significantly affect transcriptional levels and subsequently significantly influence bovine intramscular fat content.}, } @article {pmid30382813, year = {2018}, author = {Qiu, CZ and Zhou, QZ and Liu, TT and Fang, SM and Wang, YW and Fang, X and Huang, CL and Yu, QY and Chen, CH and Zhang, Z}, title = {Evidence of peripheral olfactory impairment in the domestic silkworms: insight from the comparative transcriptome and population genetics.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {788}, pmid = {30382813}, issn = {1471-2164}, support = {20152062//Promoting Cooperation of Scientific Research with the Region of America and Oceania and High-level Talents Training in Ministry of Education of China/ ; }, abstract = {BACKGROUND: The insect olfactory system is a highly specific and sensitive chemical detector, which plays important roles in feeding, mating and finding an appropriate oviposition site. The ecological niche of Bombyx mori has changed greatly since domestication from B. mandarina, and its olfactory response to environmental odorants clearly decreased. However, the mechanisms that result in the olfactory impairment are largely unknown.

RESULTS: The antennal transcriptomes were compared between the domestic and wild silkworms. Comparison of the same sex between the domestic and wild silkworms revealed 1410 and 1173 differentially expressed genes (DEGs) in males and females, respectively. To understand the olfactory impairment, we mainly focused on the olfactory-related genes. In total, 30 olfactory genes and 19 odorant-degrading enzymes (ODEs) showed differential expression in the two comparisons, in which 19 and 14 were down-regulated in the domestic silkworm, respectively. Based on population genomic data, the down-regulated odorant receptors (ORs) showed a higher ratio of unique non-synonymous polymorphisms to synonymous polymorphisms (N/S ratio) in the domestic populations than that in the wild silkworms. Furthermore, one deleterious mutation was found in OR30 of the domestic population, which was located in transmembrane helix 6 (TM6).

CONCLUSIONS: Our results suggested that down-regulation of the olfactory-related genes and relaxed selection might be the major reasons for olfactory impairment of the domestic silkworm reared completely indoor environment. Reversely, wild silkworm may increase expression and remove deleterious polymorphisms of olfactory-related genes to retain sensitive olfaction.}, } @article {pmid30382811, year = {2018}, author = {Argyriou, T and Giles, S and Friedman, M and Romano, C and Kogan, I and Sánchez-Villagra, MR}, title = {Internal cranial anatomy of Early Triassic species of †Saurichthys (Actinopterygii: †Saurichthyiformes): implications for the phylogenetic placement of †saurichthyiforms.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {161}, pmid = {30382811}, issn = {1471-2148}, mesh = {Animals ; Fishes/*anatomy & histology/*classification ; *Fossils ; Paleontology ; *Phylogeny ; Skull/*anatomy & histology/diagnostic imaging ; Time Factors ; Tomography ; }, abstract = {BACKGROUND: †Saurichthyiformes were a successful group of latest Permian-Middle Jurassic predatory actinopterygian fishes and constituted important, widely-distributed components of Triassic marine and freshwater faunas. Their systematic affinities have long been debated, with †saurichthyiforms often being aligned with chondrosteans, a group today comprising sturgeons and paddlefishes. However, their character-rich endocranial anatomy has not been investigated in detail since the first half of the 20th century. Since then, major advances have occurred in terms of our understanding of early actinopterygian anatomy, as well as techniques for extracting morphological data from fossils.

RESULTS: We used μCT to study the internal cranial anatomy of two of the stratigraphically oldest representatives of †Saurichthys, from the Early Triassic of East Greenland and Nepal. Our work revealed numerous previously unknown characters (e.g., cryptic oticooccipital fissure; intramural diverticula of braincase; nasobasal canals; lateral cranial canal; fused dermohyal), and permitted the reevalution of features relating to the structure of cranial fossae, basicranial circulation and opercular anatomy of the genus. Critically, we reinterpret the former †saurichthyiform opercle as an expanded subopercle. For comparison, we also produced the first digital models of a braincase and endocast of a sturgeon (A. brevirostrum). New information from these taxa was included in a broad phylogenetic analysis of Actinopterygii. †Saurichthyiforms are resolved as close relatives of †Birgeria, forming a clade that constitutes the immediate sister group of crown actinopterygians. However, these and other divergences near the actinopterygian crown node are weakly supported.

CONCLUSIONS: Our phylogeny disagrees with the historically prevalent hypothesis favoring the chondrostean affinities of †saurichthyiforms. Previously-proposed synapomorphies uniting the two clades, such as the closure of the oticooccipital fissure, the posterior extension of the parasphenoid, and the absence of an opercular process, are all widespread amongst actinopterygians. Others, like those relating to basicranial circulation, are found to be based on erroneous interpretations. Our work renders the †saurichthyiform character complex adequately understood, and permits detailed comparisons with other stem and crown actinopterygians. Our phylogenetic scheme highlights outstanding questions concerning the affinity of many early actinopterygians, such as the Paleozoic-early Mesozoic deep-bodied forms, which are largely caused by lack of endoskeletal data.}, } @article {pmid30382578, year = {2018}, author = {Dean, R and Hammer, C and Higham, V and Dowling, DK}, title = {Masculinization of gene expression is associated with male quality in Drosophila melanogaster.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2736-2748}, doi = {10.1111/evo.13618}, pmid = {30382578}, issn = {1558-5646}, support = {DE150101853//Australian Research Council/ ; DP120103205//Australian Research Council/ ; 655392//H2020 European Research Council/ ; }, abstract = {The signature of sexual selection has been revealed through the study of differences in patterns of genome-wide gene expression, both between the sexes and between alternative reproductive morphs within a single sex. What remains unclear, however, is whether differences in gene expression patterns between individuals of a given sex consistently map to variation in individual quality. Such a pattern, particularly if found in males, would provide unambiguous evidence that the phenotypic response to sexual selection is shaped through sex-specific alterations to the transcriptome. To redress this knowledge gap, we explored whether patterns of sex-biased gene expression are associated with variation in male reproductive quality in Drosophila melanogaster. We measured two male reproductive phenotypes, and their association with sex-biased gene expression, across a selection of inbred lines from the Drosophila Genetic Reference Panel. Genotypes with higher expression of male-biased genes produced males exhibiting shorter latencies to copulation, and higher capacity to inseminate females. Conversely, female-biased genes tended to show negative associations with these male reproductive traits across genotypes. We uncovered similar patterns, by reanalyzing a published dataset from a second D. melanogaster population. Our results reveal the footprint of sexual selection in masculinising the male transcriptome.}, } @article {pmid30382345, year = {2019}, author = {Huo, Y and Kang, JP and Ahn, JC and Yang, DU and Yang, DC}, title = {Ornithinimicrobium panacihumi sp. nov., Antagonistic Bacteria Against Root Rot Fungal Pathogens, Isolated from Cultivated Ginseng Soil.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {22-28}, doi = {10.1007/s00284-018-1579-9}, pmid = {30382345}, issn = {1432-0991}, abstract = {A Gram-positive bacterium (DCY118T) was isolated from ginseng-cultivated soil in Gochang-gun, Republic of Korea. This isolate was assigned to the genus Ornithinimicrobium and is closely related to Ornithinimicrobium kibberense K22-20T (98.8%), O. pekingense DSM 21552T (98.5%), O. algicola JC311T (98.2%), and O. humiphilum DSM 12362T (97.9%) based on 16S rRNA gene sequence analysis. However, strain DCY118T showed < 55% DNA-DNA homology with closely related reference strains. Cells were non-motile, non-sporulating, catalase- and oxidase-positive, aerobic, short rods, and cocci, and produced light-yellow, circular, and smooth colonies on TSA medium. MK-8(H4) was the predominant menaquinone. The major cellular fatty acids were iso-C15:0, anteiso-C15:0, and C16:0. The polar lipid profile consisted of diphosphatidylglycerol (DPG), phosphatidylglycerol (PG), phosphatidylinositol (PI), an unknown phospholipid (PL1), an unknown amino lipid (AL1), and unidentified polar lipids (L1-5). The genomic DNA G+C content was 71.1 mol%. The peptidoglycan contained L-ornithine as the diagnostic diamino acid. Whole-cell sugars were composed of glucose, arabinose, and xylose. Overall, data collected from phenotypic and genotypic tests during this study indicated that strain DCY118T could not be assigned to a recognized species. Strain DCY118T showed antagonistic activity against the fungal pathogens causing root rot in ginseng, i.e., Fusarium solani (KACC 44891T) and Cylindrocarpon destructans (KACC 44660T). The results from this study confirm the DCY118T strain as a new species within the genus Ornithinimicrobium, for which the name Ornithinimicrobium panacihumi is proposed. The type strain is DCY118T (=KCTC 39962T=JCM 32156T).}, } @article {pmid30382299, year = {2018}, author = {Lamolle, G and Musto, H}, title = {Why Prokaryotes Genomes Lack Genes with Introns Processed by Spliceosomes?.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {611-612}, pmid = {30382299}, issn = {1432-1432}, } @article {pmid30382233, year = {2018}, author = {}, title = {City links.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S8}, doi = {10.1038/d41586-018-07207-1}, pmid = {30382233}, issn = {1476-4687}, } @article {pmid30382232, year = {2018}, author = {Escobar, H}, title = {Standing firm.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S22-S23}, doi = {10.1038/d41586-018-07211-5}, pmid = {30382232}, issn = {1476-4687}, } @article {pmid30382231, year = {2018}, author = {Maisonobe, M and Jégou, L and Cabanac, G}, title = {Peripheral forces.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S18-S19}, doi = {10.1038/d41586-018-07210-6}, pmid = {30382231}, issn = {1476-4687}, } @article {pmid30382230, year = {2018}, author = {Jia, H}, title = {Discovery central.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S16-S17}, doi = {10.1038/d41586-018-07209-z}, pmid = {30382230}, issn = {1476-4687}, } @article {pmid30382229, year = {2018}, author = {Nordling, L}, title = {The cape of change.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S2-S3}, doi = {10.1038/d41586-018-07205-3}, pmid = {30382229}, issn = {1476-4687}, } @article {pmid30382228, year = {2018}, author = {Boytchev, H}, title = {A European heavyweight.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S14-S15}, doi = {10.1038/d41586-018-07208-0}, pmid = {30382228}, issn = {1476-4687}, } @article {pmid30382227, year = {2018}, author = {Bourzac, K}, title = {A venture under pressure.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S6-S7}, doi = {10.1038/d41586-018-07206-2}, pmid = {30382227}, issn = {1476-4687}, } @article {pmid30382226, year = {2018}, author = {Mallapaty, S}, title = {Counting capital costs.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S1}, doi = {10.1038/d41586-018-07204-4}, pmid = {30382226}, issn = {1476-4687}, } @article {pmid30382225, year = {2018}, author = {Watson, JEM and Venter, O and Lee, J and Jones, KR and Robinson, JG and Possingham, HP and Allan, JR}, title = {Protect the last of the wild.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {27-30}, doi = {10.1038/d41586-018-07183-6}, pmid = {30382225}, issn = {1476-4687}, mesh = {Animals ; Biodiversity ; Conservation of Natural Resources/*legislation & jurisprudence/*trends ; *Ecosystem ; Environmental Policy/*legislation & jurisprudence/trends ; Extinction, Biological ; Global Warming/prevention & control ; Human Activities/*legislation & jurisprudence ; International Cooperation/*legislation & jurisprudence ; Oceans and Seas ; *Wilderness ; }, } @article {pmid30382224, year = {2018}, author = {O'Meara, S}, title = {Taking the silk road to high-tech growth.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S25-S27}, doi = {10.1038/d41586-018-07202-6}, pmid = {30382224}, issn = {1476-4687}, } @article {pmid30382223, year = {2018}, author = {Fleming, N}, title = {How neuroscience is breaking out of the lab.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {S29-S31}, doi = {10.1038/d41586-018-07201-7}, pmid = {30382223}, issn = {1476-4687}, } @article {pmid30382222, year = {2018}, author = {Nowogrodzki, A}, title = {The world's strongest MRI machines are pushing human imaging to new limits.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {24-26}, doi = {10.1038/d41586-018-07182-7}, pmid = {30382222}, issn = {1476-4687}, mesh = {Humans ; Magnetic Fields ; Magnetic Resonance Imaging/economics/*instrumentation ; *Magnets/economics ; Male ; Minnesota ; Neuroimaging/economics/*instrumentation ; }, } @article {pmid30382221, year = {2018}, author = {Walker, D}, title = {Contagion in tranquil shades of grey.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {150}, doi = {10.1038/d41586-018-07200-8}, pmid = {30382221}, issn = {1476-4687}, } @article {pmid30382220, year = {2018}, author = {Venn, K}, title = {Evidence of ancient Milky Way merger.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {43-44}, doi = {10.1038/d41586-018-07193-4}, pmid = {30382220}, issn = {1476-4687}, mesh = {*Astronomical Phenomena ; *Astronomy ; }, } @article {pmid30382219, year = {2018}, author = {Bhaduri, A and Nowakowski, TJ}, title = {Single-cell sequencing paints diverse pictures of the brain.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {38-39}, doi = {10.1038/d41586-018-07027-3}, pmid = {30382219}, issn = {1476-4687}, mesh = {Brain ; *Neocortex ; *Transcriptome ; }, } @article {pmid30382218, year = {2018}, author = {Vanner, MR}, title = {Mechanical quantum systems controlled.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {39-40}, doi = {10.1038/d41586-018-07169-4}, pmid = {30382218}, issn = {1476-4687}, mesh = {Motion ; *Optics and Photonics ; *Physics ; Quantum Theory ; }, } @article {pmid30382217, year = {2018}, author = {}, title = {Brazil's controversial new president, academic freedom in Hungary and Australia, and name change for Hubble law.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {10-11}, doi = {10.1038/d41586-018-07180-9}, pmid = {30382217}, issn = {1476-4687}, } @article {pmid30382215, year = {2018}, author = {}, title = {Paralysed people walk again after spinal-cord stimulation.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {6}, doi = {10.1038/d41586-018-07237-9}, pmid = {30382215}, issn = {1476-4687}, mesh = {Humans ; Paralysis ; Spinal Cord ; *Spinal Cord Injuries ; Spinal Cord Stimulation ; *Walking ; }, } @article {pmid30382214, year = {2018}, author = {Bayry, J}, title = {Indian researchers must resist predatory open-access journals.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {35}, doi = {10.1038/d41586-018-07243-x}, pmid = {30382214}, issn = {1476-4687}, } @article {pmid30382213, year = {2018}, author = {Birkhead, TR}, title = {Brighten outlook for long-term seabird monitoring.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {35}, doi = {10.1038/d41586-018-07242-y}, pmid = {30382213}, issn = {1476-4687}, } @article {pmid30382212, year = {2018}, author = {Luckman, EA}, title = {Savvy leadership promotes ethical science.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {35}, doi = {10.1038/d41586-018-07241-z}, pmid = {30382212}, issn = {1476-4687}, mesh = {Happiness ; Laboratories/ethics ; *Leadership ; *Morals ; }, } @article {pmid30382211, year = {2018}, author = {Tubiello, FN}, title = {Make better use of UN food and agriculture stats.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {35}, doi = {10.1038/d41586-018-07239-7}, pmid = {30382211}, issn = {1476-4687}, } @article {pmid30382210, year = {2018}, author = {Bietz, A}, title = {WHO's embrace of traditional oriental medicines puts health and wildlife at risk.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {35}, doi = {10.1038/d41586-018-07240-0}, pmid = {30382210}, issn = {1476-4687}, mesh = {*Medicine, East Asian Traditional ; *World Health Organization ; }, } @article {pmid30382209, year = {2018}, author = {Landhuis, E}, title = {Tapping into the brain's star power.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {141-143}, doi = {10.1038/d41586-018-07197-0}, pmid = {30382209}, issn = {1476-4687}, } @article {pmid30382208, year = {2018}, author = {Finkbeiner, A}, title = {The covert politics of cold-war science.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {32-33}, doi = {10.1038/d41586-018-07184-5}, pmid = {30382208}, issn = {1476-4687}, } @article {pmid30382207, year = {2018}, author = {Helmi, A and Babusiaux, C and Koppelman, HH and Massari, D and Veljanoski, J and Brown, AGA}, title = {The merger that led to the formation of the Milky Way's inner stellar halo and thick disk.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {85-88}, doi = {10.1038/s41586-018-0625-x}, pmid = {30382207}, issn = {1476-4687}, abstract = {The assembly of our Galaxy can be reconstructed using the motions and chemistry of individual stars1,2. Chemo-dynamical studies of the stellar halo near the Sun have indicated the presence of multiple components3, such as streams4 and clumps5, as well as correlations between the stars' chemical abundances and orbital parameters6-8. Recently, analyses of two large stellar surveys9,10 revealed the presence of a well populated elemental abundance sequence7,11, two distinct sequences in the colour-magnitude diagram12 and a prominent, slightly retrograde kinematic structure13,14 in the halo near the Sun, which may trace an important accretion event experienced by the Galaxy15. However, the link between these observations and their implications for Galactic history is not well understood. Here we report an analysis of the kinematics, chemistry, age and spatial distribution of stars that are mainly linked to two major Galactic components: the thick disk and the stellar halo. We demonstrate that the inner halo is dominated by debris from an object that at infall was slightly more massive than the Small Magellanic Cloud, and which we refer to as Gaia-Enceladus. The stars that originate in Gaia-Enceladus cover nearly the full sky, and their motions reveal the presence of streams and slightly retrograde and elongated trajectories. With an estimated mass ratio of four to one, the merger of the Milky Way with Gaia-Enceladus must have led to the dynamical heating of the precursor of the Galactic thick disk, thus contributing to the formation of this component approximately ten billion years ago. These findings are in line with the results of galaxy formation simulations, which predict that the inner stellar halo should be dominated by debris from only a few massive progenitors2,16.}, } @article {pmid30382206, year = {2018}, author = {Rypdal, M and Fredriksen, HB and Rypdal, K and Steene, RJ}, title = {Emergent constraints on climate sensitivity.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {E4-E5}, doi = {10.1038/s41586-018-0639-4}, pmid = {30382206}, issn = {1476-4687}, } @article {pmid30382205, year = {2018}, author = {Po-Chedley, S and Proistosescu, C and Armour, KC and Santer, BD}, title = {Climate constraint reflects forced signal.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {E6-E9}, doi = {10.1038/s41586-018-0640-y}, pmid = {30382205}, issn = {1476-4687}, } @article {pmid30382204, year = {2018}, author = {Cox, PM and Williamson, MS and Nijsse, FJMM and Huntingford, C}, title = {Cox et al. reply.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {E10-E15}, doi = {10.1038/s41586-018-0641-x}, pmid = {30382204}, issn = {1476-4687}, } @article {pmid30382203, year = {2018}, author = {Brown, PT and Stolpe, MB and Caldeira, K}, title = {Assumptions for emergent constraints.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {E1-E3}, doi = {10.1038/s41586-018-0638-5}, pmid = {30382203}, issn = {1476-4687}, } @article {pmid30382202, year = {2018}, author = {Rossi, M and Mason, D and Chen, J and Tsaturyan, Y and Schliesser, A}, title = {Measurement-based quantum control of mechanical motion.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {53-58}, doi = {10.1038/s41586-018-0643-8}, pmid = {30382202}, issn = {1476-4687}, abstract = {Controlling a quantum system by using observations of its dynamics is complicated by the backaction of the measurement process-that is, the unavoidable quantum disturbance caused by coupling the system to a measurement apparatus. An efficient measurement is one that maximizes the amount of information gained per disturbance incurred. Real-time feedback can then be used to cancel the backaction of the measurement and to control the evolution of the quantum state. Such measurement-based quantum control has been demonstrated in the clean settings of cavity and circuit quantum electrodynamics, but its application to motional degrees of freedom has remained elusive. Here we demonstrate measurement-based quantum control of the motion of a millimetre-sized membrane resonator. An optomechanical transducer resolves the zero-point motion of the resonator in a fraction of its millisecond-scale coherence time, with an overall measurement efficiency close to unity. An electronic feedback loop converts this position record to a force that cools the resonator mode to its quantum ground state (residual thermal occupation of about 0.29). This occupation is nine decibels below the quantum-backaction limit of sideband cooling and six orders of magnitude below the equilibrium occupation of the thermal environment. We thus realize a long-standing goal in the field, adding position and momentum to the degrees of freedom that are amenable to measurement-based quantum control, with potential applications in quantum information processing and gravitational-wave detectors.}, } @article {pmid30382201, year = {2018}, author = {Resplandy, L and Keeling, RF and Eddebbar, Y and Brooks, MK and Wang, R and Bopp, L and Long, MC and Dunne, JP and Koeve, W and Oschlies, A}, title = {Quantification of ocean heat uptake from changes in atmospheric O2 and CO2 composition.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {105-108}, doi = {10.1038/s41586-018-0651-8}, pmid = {30382201}, issn = {1476-4687}, abstract = {The ocean is the main source of thermal inertia in the climate system1. During recent decades, ocean heat uptake has been quantified by using hydrographic temperature measurements and data from the Argo float program, which expanded its coverage after 20072,3. However, these estimates all use the same imperfect ocean dataset and share additional uncertainties resulting from sparse coverage, especially before 20074,5. Here we provide an independent estimate by using measurements of atmospheric oxygen (O2) and carbon dioxide (CO2)-levels of which increase as the ocean warms and releases gases-as a whole-ocean thermometer. We show that the ocean gained 1.33 ± 0.20 × 1022 joules of heat per year between 1991 and 2016, equivalent to a planetary energy imbalance of 0.83 ± 0.11 watts per square metre of Earth's surface. We also find that the ocean-warming effect that led to the outgassing of O2 and CO2 can be isolated from the direct effects of anthropogenic emissions and CO2 sinks. Our result-which relies on high-precision O2 measurements dating back to 19916-suggests that ocean warming is at the high end of previous estimates, with implications for policy-relevant measurements of the Earth response to climate change, such as climate sensitivity to greenhouse gases7 and the thermal component of sea-level rise8.}, } @article {pmid30382200, year = {2018}, author = {Economo, MN and Viswanathan, S and Tasic, B and Bas, E and Winnubst, J and Menon, V and Graybuck, LT and Nguyen, TN and Smith, KA and Yao, Z and Wang, L and Gerfen, CR and Chandrashekar, J and Zeng, H and Looger, LL and Svoboda, K}, title = {Distinct descending motor cortex pathways and their roles in movement.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {79-84}, doi = {10.1038/s41586-018-0642-9}, pmid = {30382200}, issn = {1476-4687}, support = {U01 MH105982/MH/NIMH NIH HHS/United States ; ZIA-MH002497-29/MH/NIMH NIH HHS/United States ; }, abstract = {Activity in the motor cortex predicts movements, seconds before they are initiated. This preparatory activity has been observed across cortical layers, including in descending pyramidal tract neurons in layer 5. A key question is how preparatory activity is maintained without causing movement, and is ultimately converted to a motor command to trigger appropriate movements. Here, using single-cell transcriptional profiling and axonal reconstructions, we identify two types of pyramidal tract neuron. Both types project to several targets in the basal ganglia and brainstem. One type projects to thalamic regions that connect back to motor cortex; populations of these neurons produced early preparatory activity that persisted until the movement was initiated. The second type projects to motor centres in the medulla and mainly produced late preparatory activity and motor commands. These results indicate that two types of motor cortex output neurons have specialized roles in motor control.}, } @article {pmid30382199, year = {2018}, author = {Burch, KS and Mandrus, D and Park, JG}, title = {Magnetism in two-dimensional van der Waals materials.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {47-52}, doi = {10.1038/s41586-018-0631-z}, pmid = {30382199}, issn = {1476-4687}, support = {DMR-1709987//National Science Foundation/International ; DMR-1410428//National Science Foundation/International ; }, abstract = {The discovery of materials has often introduced new physical paradigms and enabled the development of novel devices. Two-dimensional magnetism, which is associated with strong intrinsic spin fluctuations, has long been the focus of fundamental questions in condensed matter physics regarding our understanding and control of new phases. Here we discuss magnetic van der Waals materials: two-dimensional atomic crystals that contain magnetic elements and thus exhibit intrinsic magnetic properties. These cleavable materials provide the ideal platform for exploring magnetism in the two-dimensional limit, where new physical phenomena are expected, and represent a substantial shift in our ability to control and investigate nanoscale phases. We present the theoretical background and motivation for investigating this class of crystals, describe the material landscape and the current experimental status of measurement techniques as well as devices, and discuss promising future directions for the study of magnetic van der Waals materials.}, } @article {pmid30382198, year = {2018}, author = {Tasic, B and Yao, Z and Graybuck, LT and Smith, KA and Nguyen, TN and Bertagnolli, D and Goldy, J and Garren, E and Economo, MN and Viswanathan, S and Penn, O and Bakken, T and Menon, V and Miller, J and Fong, O and Hirokawa, KE and Lathia, K and Rimorin, C and Tieu, M and Larsen, R and Casper, T and Barkan, E and Kroll, M and Parry, S and Shapovalova, NV and Hirschstein, D and Pendergraft, J and Sullivan, HA and Kim, TK and Szafer, A and Dee, N and Groblewski, P and Wickersham, I and Cetin, A and Harris, JA and Levi, BP and Sunkin, SM and Madisen, L and Daigle, TL and Looger, L and Bernard, A and Phillips, J and Lein, E and Hawrylycz, M and Svoboda, K and Jones, AR and Koch, C and Zeng, H}, title = {Shared and distinct transcriptomic cell types across neocortical areas.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {72-78}, doi = {10.1038/s41586-018-0654-5}, pmid = {30382198}, issn = {1476-4687}, support = {R01 EY023173/EY/NEI NIH HHS/United States ; U01 MH105982/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/analysis ; Female ; GABAergic Neurons/metabolism ; *Gene Expression Profiling ; Glutamic Acid/metabolism ; Male ; Mice ; Motor Cortex/anatomy & histology/cytology/metabolism ; Neocortex/anatomy & histology/*cytology/*metabolism ; Organ Specificity ; Sequence Analysis, RNA ; Single-Cell Analysis ; Visual Cortex/anatomy & histology/cytology/metabolism ; }, abstract = {The neocortex contains a multitude of cell types that are segregated into layers and functionally distinct areas. To investigate the diversity of cell types across the mouse neocortex, here we analysed 23,822 cells from two areas at distant poles of the mouse neocortex: the primary visual cortex and the anterior lateral motor cortex. We define 133 transcriptomic cell types by deep, single-cell RNA sequencing. Nearly all types of GABA (γ-aminobutyric acid)-containing neurons are shared across both areas, whereas most types of glutamatergic neurons were found in one of the two areas. By combining single-cell RNA sequencing and retrograde labelling, we match transcriptomic types of glutamatergic neurons to their long-range projection specificity. Our study establishes a combined transcriptomic and projectional taxonomy of cortical cell types from functionally distinct areas of the adult mouse cortex.}, } @article {pmid30382197, year = {2018}, author = {Wagner, FB and Mignardot, JB and Le Goff-Mignardot, CG and Demesmaeker, R and Komi, S and Capogrosso, M and Rowald, A and Seáñez, I and Caban, M and Pirondini, E and Vat, M and McCracken, LA and Heimgartner, R and Fodor, I and Watrin, A and Seguin, P and Paoles, E and Van Den Keybus, K and Eberle, G and Schurch, B and Pralong, E and Becce, F and Prior, J and Buse, N and Buschman, R and Neufeld, E and Kuster, N and Carda, S and von Zitzewitz, J and Delattre, V and Denison, T and Lambert, H and Minassian, K and Bloch, J and Courtine, G}, title = {Targeted neurotechnology restores walking in humans with spinal cord injury.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {65-71}, doi = {10.1038/s41586-018-0649-2}, pmid = {30382197}, issn = {1476-4687}, abstract = {Spinal cord injury leads to severe locomotor deficits or even complete leg paralysis. Here we introduce targeted spinal cord stimulation neurotechnologies that enabled voluntary control of walking in individuals who had sustained a spinal cord injury more than four years ago and presented with permanent motor deficits or complete paralysis despite extensive rehabilitation. Using an implanted pulse generator with real-time triggering capabilities, we delivered trains of spatially selective stimulation to the lumbosacral spinal cord with timing that coincided with the intended movement. Within one week, this spatiotemporal stimulation had re-established adaptive control of paralysed muscles during overground walking. Locomotor performance improved during rehabilitation. After a few months, participants regained voluntary control over previously paralysed muscles without stimulation and could walk or cycle in ecological settings during spatiotemporal stimulation. These results establish a technological framework for improving neurological recovery and supporting the activities of daily living after spinal cord injury.}, } @article {pmid30382193, year = {2018}, author = {Roque, JB and Kuroda, Y and Göttemann, LT and Sarpong, R}, title = {Deconstructive diversification of cyclic amines.}, journal = {Nature}, volume = {564}, number = {7735}, pages = {244-248}, doi = {10.1038/s41586-018-0700-3}, pmid = {30382193}, issn = {1476-4687}, support = {R01 GM086374/GM/NIGMS NIH HHS/United States ; }, abstract = {Deconstructive functionalization involves carbon-carbon (C-C) bond cleavage followed by bond construction on one or more of the constituent carbons. For example, ozonolysis1 and olefin metathesis2,3 have allowed each carbon in C=C double bonds to be viewed as a functional group. Despite the substantial advances in deconstructive functionalization involving the scission of C=C double bonds, there are very few methods that achieve C(sp3)-C(sp3) single-bond cleavage and functionalization, especially in relatively unstrained cyclic systems. Here we report a deconstructive strategy to transform saturated nitrogen heterocycles such as piperidines and pyrrolidines, which are important moieties in bioactive molecules, into halogen-containing acyclic amine derivatives through sequential C(sp3)-N and C(sp3)-C(sp3) single-bond cleavage followed by C(sp3)-halogen bond formation. The resulting acyclic haloamines are versatile intermediates that can be transformed into various structural motifs through substitution reactions. In this way we achieve the skeletal remodelling of cyclic amines, an example of scaffold hopping. We demonstrate this deconstructive strategy by the late-stage diversification of proline-containing peptides.}, } @article {pmid30381462, year = {2018}, author = {Amelio, I and Mancini, M and Petrova, V and Cairns, RA and Vikhreva, P and Nicolai, S and Marini, A and Antonov, AA and Le Quesne, J and Baena Acevedo, JD and Dudek, K and Sozzi, G and Pastorino, U and Knight, RA and Mak, TW and Melino, G}, title = {p53 mutants cooperate with HIF-1 in transcriptional regulation of extracellular matrix components to promote tumor progression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10869-E10878}, pmid = {30381462}, issn = {1091-6490}, mesh = {Animals ; Carcinoma, Non-Small-Cell Lung/*genetics/metabolism/pathology ; Cell Hypoxia/genetics ; Cell Line, Tumor ; Extracellular Matrix ; Genes, p53 ; Heterografts ; Humans ; Hypoxia-Inducible Factor 1/*genetics/metabolism ; Lung Neoplasms/*genetics/metabolism/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mutation ; Transcriptional Activation ; Tumor Microenvironment ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Mutations in the TP53 gene and microenvironmentally driven activation of hypoxia-inducible factor-1 (HIF-1) typically occur in later stages of tumorigenesis. An ongoing challenge is the identification of molecular determinants of advanced cancer pathogenesis to design alternative last-line therapeutic options. Here, we report that p53 mutants influence the tumor microenvironment by cooperating with HIF-1 to promote cancer progression. We demonstrate that in non-small cell lung cancer (NSCLC), p53 mutants exert a gain-of-function (GOF) effect on HIF-1, thus regulating a selective gene expression signature involved in protumorigenic functions. Hypoxia-mediated activation of HIF-1 leads to the formation of a p53 mutant/HIF-1 complex that physically binds the SWI/SNF chromatin remodeling complex, promoting expression of a selective subset of hypoxia-responsive genes. Depletion of p53 mutants impairs the HIF-mediated up-regulation of extracellular matrix (ECM) components, including type VIIa1 collagen and laminin-γ2, thus affecting tumorigenic potential of NSCLC cells in vitro and in mouse models in vivo. Analysis of surgically resected human NSCLC revealed that expression of this ECM gene signature was highly correlated with hypoxic tumors exclusively in patients carrying p53 mutations and was associated with poor prognosis. Our data reveal a GOF effect of p53 mutants in hypoxic tumors and suggest synergistic activities of p53 and HIF-1. These findings have important implications for cancer progression and might provide innovative last-line treatment options for advanced NSCLC.}, } @article {pmid30381461, year = {2018}, author = {Lécrivain, AL and Le Rhun, A and Renault, TT and Ahmed-Begrich, R and Hahnke, K and Charpentier, E}, title = {In vivo 3'-to-5' exoribonuclease targetomes of Streptococcus pyogenes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11814-11819}, pmid = {30381461}, issn = {1091-6490}, mesh = {Exoribonucleases/*metabolism/physiology ; Gene Expression Regulation, Bacterial/genetics ; Polyribonucleotide Nucleotidyltransferase/metabolism ; RNA Stability/genetics/*physiology ; RNA, Bacterial/genetics ; RNA, Messenger/metabolism ; Streptococcus pyogenes/*genetics ; }, abstract = {mRNA decay plays an essential role in the control of gene expression in bacteria. Exoribonucleases (exoRNases), which trim transcripts starting from the 5' or 3' end, are particularly important to fully degrade unwanted transcripts and renew the pool of nucleotides available in the cell. While recent techniques have allowed genome-wide identification of ribonuclease (RNase) targets in bacteria in vivo, none of the 3'-to-5' exoRNase targetomes (i.e., global processing sites) have been studied so far. Here, we report the targetomes of YhaM, polynucleotide phosphorylase (PNPase), and RNase R of the human pathogen Streptococcus pyogenes We determined that YhaM is an unspecific enzyme that trims a few nucleotides and targets the majority of transcript ends, generated either by transcription termination or by endonucleolytic activity. The molecular determinants for YhaM-limited processivity are yet to be deciphered. We showed that PNPase clears the cell from mRNA decay fragments produced by endoribonucleases (endoRNases) and is the major 3'-to-5' exoRNase for RNA turnover in S. pyogenes In particular, PNPase is responsible for the degradation of regulatory elements from 5' untranslated regions. However, we observed little RNase R activity in standard culture conditions. Overall, our study sheds light on the very distinct features of S. pyogenes 3'-to-5' exoRNases.}, } @article {pmid30381460, year = {2018}, author = {Shi, L and Li, K and Guo, Y and Banerjee, A and Wang, Q and Lorenz, UM and Parlak, M and Sullivan, LC and Onyema, OO and Arefanian, S and Stelow, EB and Brautigan, DL and Bullock, TNJ and Brown, MG and Krupnick, AS}, title = {Modulation of NKG2D, NKp46, and Ly49C/I facilitates natural killer cell-mediated control of lung cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11808-11813}, pmid = {30381460}, issn = {1091-6490}, support = {R41 CA224520/CA/NCI NIH HHS/United States ; P30 CA044579/CA/NCI NIH HHS/United States ; R01 AI050072/AI/NIAID NIH HHS/United States ; P01 AI116501/AI/NIAID NIH HHS/United States ; I01 BX002299/BX/BLRD VA/United States ; }, mesh = {Animals ; Antigens, Ly/*immunology ; Cytotoxicity, Immunologic ; Down-Regulation ; Histocompatibility Antigens Class I/metabolism ; Killer Cells, Natural/*immunology ; Lung Neoplasms/*immunology/metabolism ; Mice ; Mice, Inbred C57BL ; NK Cell Lectin-Like Receptor Subfamily A/*immunology ; NK Cell Lectin-Like Receptor Subfamily K/*immunology ; Natural Cytotoxicity Triggering Receptor 1/*immunology ; Receptors, Immunologic/*immunology ; Receptors, Natural Killer Cell/*metabolism ; Up-Regulation ; }, abstract = {Natural killer (NK) cells play a critical role in controlling malignancies. Susceptibility or resistance to lung cancer, for example, specifically depends on NK cell function. Nevertheless, intrinsic factors that control NK cell-mediated clearance of lung cancer are unknown. Here we report that NK cells exposed to exogenous major histocompatibility class I (MHCI) provide a significant immunologic barrier to the growth and progression of malignancy. Clearance of lung cancer is facilitated by up-regulation of NKG2D, NKp46, and other activating receptors upon exposure to environmental MHCI. Surface expression of the inhibitory receptor Ly49C/I, on the other hand, is down-regulated upon exposure to tumor-bearing tissue. We thus demonstrate that NK cells exhibit dynamic plasticity in surface expression of both activating and inhibitory receptors based on the environmental context. Our data suggest that altering the activation state of NK cells may contribute to immunologic control of lung and possibly other cancers.}, } @article {pmid30381459, year = {2018}, author = {DiTommaso, T and Cole, JM and Cassereau, L and Buggé, JA and Hanson, JLS and Bridgen, DT and Stokes, BD and Loughhead, SM and Beutel, BA and Gilbert, JB and Nussbaum, K and Sorrentino, A and Toggweiler, J and Schmidt, T and Gyuelveszi, G and Bernstein, H and Sharei, A}, title = {Cell engineering with microfluidic squeezing preserves functionality of primary immune cells in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10907-E10914}, pmid = {30381459}, issn = {1091-6490}, support = {R44 GM116312/GM/NIGMS NIH HHS/United States ; U54 TR001012/TR/NCATS NIH HHS/United States ; }, mesh = {Cell Engineering/*methods ; Dendritic Cells/immunology ; Electroporation/methods ; Humans ; Microfluidics/*methods ; RNA, Messenger/metabolism ; T-Lymphocytes/immunology ; Transcriptome ; }, abstract = {The translational potential of cell-based therapies is often limited by complications related to effectively engineering and manufacturing functional cells. While the use of electroporation is widespread, the impact of electroporation on cell state and function has yet to be fully characterized. Here, we use a genome-wide approach to study optimized electroporation treatment and identify striking disruptions in the expression profiles of key functional transcripts of human T cells. These genetic disruptions result in concomitant perturbation of cytokine secretion including a 648-fold increase in IL-2 secretion (P < 0.01) and a 30-fold increase in IFN-γ secretion (P < 0.05). Ultimately, the effects at the transcript and protein level resulted in functional deficiencies in vivo, with electroporated T cells failing to demonstrate sustained antigen-specific effector responses when subjected to immunological challenge. In contrast, cells subjected to a mechanical membrane disruption-based delivery mechanism, cell squeezing, had minimal aberrant transcriptional responses [0% of filtered genes misregulated, false discovery rate (FDR) q < 0.1] relative to electroporation (17% of genes misregulated, FDR q < 0.1) and showed undiminished effector responses, homing capabilities, and therapeutic potential in vivo. In a direct comparison of functionality, T cells edited for PD-1 via electroporation failed to distinguish from untreated controls in a therapeutic tumor model, while T cells edited with similar efficiency via cell squeezing demonstrated the expected tumor-killing advantage. This work demonstrates that the delivery mechanism used to insert biomolecules affects functionality and warrants further study.}, } @article {pmid30381458, year = {2018}, author = {Sarhan, J and Liu, BC and Muendlein, HI and Li, P and Nilson, R and Tang, AY and Rongvaux, A and Bunnell, SC and Shao, F and Green, DR and Poltorak, A}, title = {Caspase-8 induces cleavage of gasdermin D to elicit pyroptosis during Yersinia infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10888-E10897}, pmid = {30381458}, issn = {1091-6490}, support = {R21 AI135369/AI/NIAID NIH HHS/United States ; T32 AI007077/AI/NIAID NIH HHS/United States ; T32 GM008448/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/physiology ; Apoptosis Regulatory Proteins/*metabolism ; Bacterial Proteins/metabolism ; Caspase 8/*metabolism ; Humans ; Interleukin-1/metabolism ; Lipopolysaccharides/pharmacology ; MAP Kinase Kinase Kinases/antagonists & inhibitors/metabolism ; Macrophages/metabolism ; Mice ; Mice, Inbred C57BL ; Pyroptosis/physiology ; Yersinia Infections/*metabolism/pathology ; Yersinia pseudotuberculosis/metabolism ; }, abstract = {Cell death and inflammation are intimately linked during Yersinia infection. Pathogenic Yersinia inhibits the MAP kinase TGFβ-activated kinase 1 (TAK1) via the effector YopJ, thereby silencing cytokine expression while activating caspase-8-mediated cell death. Here, using Yersinia pseudotuberculosis in corroboration with costimulation of lipopolysaccharide and (5Z)-7-Oxozeaenol, a small-molecule inhibitor of TAK1, we show that caspase-8 activation during TAK1 inhibition results in cleavage of both gasdermin D (GSDMD) and gasdermin E (GSDME) in murine macrophages, resulting in pyroptosis. Loss of GsdmD delays membrane rupture, reverting the cell-death morphology to apoptosis. We found that the Yersinia-driven IL-1 response arises from asynchrony of macrophage death during bulk infections in which two cellular populations are required to provide signal 1 and signal 2 for IL-1α/β release. Furthermore, we found that human macrophages are resistant to YopJ-mediated pyroptosis, with dampened IL-1β production. Our results uncover a form of caspase-8-mediated pyroptosis and suggest a hypothesis for the increased sensitivity of humans to Yersinia infection compared with the rodent reservoir.}, } @article {pmid30381457, year = {2018}, author = {Brito, C and Ikeda, H and Urbani, P and Wyart, M and Zamponi, F}, title = {Universality of jamming of nonspherical particles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11736-11741}, pmid = {30381457}, issn = {1091-6490}, abstract = {Amorphous packings of nonspherical particles such as ellipsoids and spherocylinders are known to be hypostatic: The number of mechanical contacts between particles is smaller than the number of degrees of freedom, thus violating Maxwell's mechanical stability criterion. In this work, we propose a general theory of hypostatic amorphous packings and the associated jamming transition. First, we show that many systems fall into a same universality class. As an example, we explicitly map ellipsoids into a system of "breathing" particles. We show by using a marginal stability argument that in both cases jammed packings are hypostatic and that the critical exponents related to the contact number and the vibrational density of states are the same. Furthermore, we introduce a generalized perceptron model which can be solved analytically by the replica method. The analytical solution predicts critical exponents in the same hypostatic jamming universality class. Our analysis further reveals that the force and gap distributions of hypostatic jamming do not show power-law behavior, in marked contrast to the isostatic jamming of spherical particles. Finally, we confirm our theoretical predictions by numerical simulations.}, } @article {pmid30381456, year = {2018}, author = {Jin, L and Wang, J and Guan, F and Zhang, J and Yu, S and Liu, S and Xue, Y and Li, L and Wu, S and Wang, X and Yang, Y and Abdelgaffar, H and Jurat-Fuentes, JL and Tabashnik, BE and Wu, Y}, title = {Dominant point mutation in a tetraspanin gene associated with field-evolved resistance of cotton bollworm to transgenic Bt cotton.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11760-11765}, pmid = {30381456}, issn = {1091-6490}, mesh = {Animals ; Animals, Genetically Modified/genetics ; Bacillus thuringiensis/genetics ; Bacterial Proteins/metabolism ; China ; Evolution, Molecular ; Genome-Wide Association Study ; Gossypium/genetics ; Insecticide Resistance/*genetics ; Insecticides/metabolism ; Larva/genetics/metabolism ; Moths/*genetics ; Pest Control, Biological ; Plants, Genetically Modified/genetics ; Point Mutation/genetics ; Tetraspanins/*genetics ; }, abstract = {Extensive planting of crops genetically engineered to produce insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) has suppressed some major pests, reduced insecticide sprays, enhanced pest control by natural enemies, and increased grower profits. However, rapid evolution of resistance in pests is reducing these benefits. Better understanding of the genetic basis of resistance to Bt crops is urgently needed to monitor, delay, and counter pest resistance. We discovered that a point mutation in a previously unknown tetraspanin gene in the cotton bollworm (Helicoverpa armigera), a devastating global pest, confers dominant resistance to Cry1Ac, the sole Bt protein produced by transgenic cotton planted in China. We found the mutation using a genome-wide association study, followed by fine-scale genetic mapping and DNA sequence comparisons between resistant and susceptible strains. CRISPR/Cas9 knockout of the tetraspanin gene restored susceptibility to a resistant strain, whereas inserting the mutation conferred 125-fold resistance in a susceptible strain. DNA screening of moths captured from 23 field sites in six provinces of northern China revealed a 100-fold increase in the frequency of this mutation, from 0.001 in 2006 to 0.10 in 2016. The correspondence between the observed trajectory of the mutation and the trajectory predicted from simulation modeling shows that the dominance of the mutation accelerated adaptation. Proactive identification and tracking of the tetraspanin mutation demonstrate the potential for genomic analysis, gene editing, and molecular monitoring to improve management of resistance.}, } @article {pmid30381455, year = {2018}, author = {Yu, D and Wang, J and Zou, H and Feng, T and Chen, L and Li, J and Qi, X and Li, Z and Duan, X and Xu, C and Zhang, L and Long, X and Lan, J and Chen, C and Wang, C and Xu, X and Ren, J and Zhao, Y and Hu, X and Lian, Z and Men, H and Pan, D and Li, N and Capecchi, MR and Du, X and Zhao, Y and Wu, S}, title = {Silencing of retrotransposon-derived imprinted gene RTL1 is the main cause for postimplantational failures in mammalian cloning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11071-E11080}, pmid = {30381455}, issn = {1091-6490}, mesh = {Animals ; DNA Methylation/*genetics ; Embryo Transfer/adverse effects ; Embryo, Mammalian/cytology ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/genetics ; Genomic Imprinting/*genetics ; Induced Pluripotent Stem Cells/*cytology ; Nuclear Transfer Techniques ; Pregnancy ; Pregnancy Complications/*genetics ; Repressor Proteins/*genetics ; Retroelements/*genetics ; Swine ; }, abstract = {Substantial rates of fetal loss plague all in vitro procedures involving embryo manipulations, including human-assisted reproduction, and are especially problematic for mammalian cloning where over 90% of reconstructed nuclear transfer embryos are typically lost during pregnancy. However, the epigenetic mechanism of these pregnancy failures has not been well described. Here we performed methylome and transcriptome analyses of pig induced pluripotent stem cells and associated cloned embryos, and revealed that aberrant silencing of imprinted genes, in particular the retrotransposon-derived RTL1 gene, is the principal epigenetic cause of pregnancy failure. Remarkably, restoration of RTL1 expression in pig induced pluripotent stem cells rescued fetal loss. Furthermore, in other mammals, including humans, low RTL1 levels appear to be the main epigenetic cause of pregnancy failure.}, } @article {pmid30381454, year = {2018}, author = {Jayawardena, N and Burga, LN and Easingwood, RA and Takizawa, Y and Wolf, M and Bostina, M}, title = {Structural basis for anthrax toxin receptor 1 recognition by Seneca Valley Virus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10934-E10940}, pmid = {30381454}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Antigens, Bacterial/metabolism ; Bacillus anthracis/metabolism ; Bacterial Toxins/metabolism ; Capsid Proteins/chemistry/metabolism ; Host Specificity ; Humans ; Models, Molecular ; Neoplasm Proteins/*chemistry/genetics/*metabolism ; Oncolytic Virotherapy ; Picornaviridae/genetics/*metabolism ; Protein Binding ; Receptors, Cell Surface/*chemistry/genetics/*metabolism ; Receptors, Peptide/genetics/metabolism ; Structure-Activity Relationship ; }, abstract = {Recently, the use of oncolytic viruses in cancer therapy has become a realistic therapeutic option. Seneca Valley Virus (SVV) is a newly discovered picornavirus, which has earned a significant reputation as a potent oncolytic agent. Anthrax toxin receptor 1 (ANTXR1), one of the cellular receptors for the protective antigen secreted by Bacillus anthracis, has been identified as the high-affinity cellular receptor for SVV. Here, we report the structure of the SVV-ANTXR1 complex determined by single-particle cryo-electron microscopy analysis at near-atomic resolution. This is an example of a shared receptor structure between a mammalian virus and a bacterial toxin. Our structure shows that ANTXR1 decorates the outer surface of the SVV capsid and interacts with the surface-exposed BC loop and loop II of VP1, "the puff" of VP2 and "the knob" of VP3. Comparison of the receptor-bound capsid structure with the native capsid structure reveals that receptor binding induces minor conformational changes in SVV capsid structure, suggesting the role of ANTXR1 as an attachment receptor. Furthermore, our results demonstrate that the capsid footprint on the receptor is not conserved in anthrax toxin receptor 2 (ANTXR2), thereby providing a molecular mechanism for explaining the exquisite selectivity of SVV for ANTXR1.}, } @article {pmid30380919, year = {2018}, author = {Hernández Blasi, C and Mondéjar, L}, title = {Testing the Kundera Hypothesis: Does Every Woman (But Not Every Man) Prefer Her Child to Her Mate?.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918808864}, doi = {10.1177/1474704918808864}, pmid = {30380919}, issn = {1474-7049}, abstract = {The context of a famous novel by Milan Kundera (Immortality) suggests that when faced with a life-or-death situation, every woman would prefer to save her child than her husband, left hanging whether every man would do the same. We labeled this as the Kundera hypothesis, and the purpose of this study was to test it empirically as we believe it raises a thought-provoking question in evolutionary terms. Specifically, 197 college students (92 women) were presented a questionnaire where they had to make different decisions about four dilemmas about who to save (their mate or their offspring) in two hypothetical life-or-death situations: a home fire and a car crash. These dilemmas involved two different mate ages (a 25- or a 40-year-old mate) and two offspring ages (1- or a 6-year-old child). For comparative purposes, we also included complementary life-or-death dilemmas on both a sibling and an offspring, and a sibling and a cousin. The results generally supported the Kundera hypothesis: Although the majority of men and women made the decision to save their offspring instead of their mate, about 18% of men on average (unlike the 5% of women) consistently decided to save their mate across the four dilemmas in the two life-or-death situations. These data were interpreted with reference to Hamilton's inclusive fitness theory, the preferential role of women as kin keepers, and the evolution of altruism toward friends and mates.}, } @article {pmid30380540, year = {2018}, author = {Catania, KC}, title = {How Not to Be Turned into a Zombie.}, journal = {Brain, behavior and evolution}, volume = {92}, number = {1-2}, pages = {32-46}, doi = {10.1159/000490341}, pmid = {30380540}, issn = {1421-9743}, abstract = {The emerald jewel wasp (Ampulex compressa) is renowned for its ability to zombify the American cockroach (Periplaneta americana) with a sting to the brain. When the venom takes effect, the cockroach becomes passive and can be led by its antenna into a hole, where the wasp deposits an egg and then seals the exit with debris. The cockroach has the ability to walk, run, or fly if properly stimulated, but it does not try to escape as it is slowly eaten alive by the developing wasp larva. Although the composition and effects of the wasp's venom have been investigated, no studies have detailed how cockroaches might prevent this grim fate. Here it is shown that many cockroaches deter wasps with a vigorous defense. Successful cockroaches elevated their bodies, bringing their neck out of reach, and kicked at the wasp with their spiny hind legs, often striking the wasp's head multiple times. Failing this, the elevated, "on-guard" position allowed cockroaches to detect and evade the wasp's lunging attack. If grasped, the cockroaches parried the stinger with their legs, used a "stiff-arm" defense to hold back the stinger, and could stab at, and dislodge, the wasp with tibial spines. Lastly, cockroaches bit at the abdomen of wasps delivering the brain sting. An aggressive defense from the outset was most successful. Thus, for a cockroach not to become a zombie, the best strategy is: be vigilant, protect your throat, and strike repeatedly at the head of the attacker.}, } @article {pmid30380054, year = {2018}, author = {Hofstatter, PG and Brown, MW and Lahr, DJG}, title = {Comparative Genomics Supports Sex and Meiosis in Diverse Amoebozoa.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3118-3128}, pmid = {30380054}, issn = {1759-6653}, abstract = {Sex and reproduction are often treated as a single phenomenon in animals and plants, as in these organisms reproduction implies mixis and meiosis. In contrast, sex and reproduction are independent biological phenomena that may or may not be linked in the majority of other eukaryotes. Current evidence supports a eukaryotic ancestor bearing a mating type system and meiosis, which is a process exclusive to eukaryotes. Even though sex is ancestral, the literature regarding life cycles of amoeboid lineages depicts them as asexual organisms. Why would loss of sex be common in amoebae, if it is rarely lost, if ever, in plants and animals, as well as in fungi? One way to approach the question of meiosis in the "asexuals" is to evaluate the patterns of occurrence of genes for the proteins involved in syngamy and meiosis. We have applied a comparative genomic approach to study the occurrence of the machinery for plasmogamy, karyogamy, and meiosis in Amoebozoa, a major amoeboid supergroup. Our results support a putative occurrence of syngamy and meiotic processes in all major amoebozoan lineages. We conclude that most amoebozoans may perform mixis, recombination, and ploidy reduction through canonical meiotic processes. The present evidence indicates the possibility of sexual cycles in many lineages traditionally held as asexual.}, } @article {pmid30378594, year = {2018}, author = {Muñoz-Cánoves, P and Huch, M}, title = {Definitions for adult stem cells debated.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {328-329}, doi = {10.1038/d41586-018-07175-6}, pmid = {30378594}, issn = {1476-4687}, } @article {pmid30378593, year = {2018}, author = {Warren, M}, title = {Rotating plots to form diamonds could prevent correlation-causation confusion.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-018-06912-1}, pmid = {30378593}, issn = {1476-4687}, } @article {pmid30378592, year = {2018}, author = {Rehm, J}, title = {US government failing to provide recovery plans for some endangered species.}, journal = {Nature}, volume = {}, number = {}, pages = {}, doi = {10.1038/d41586-018-06064-2}, pmid = {30378592}, issn = {1476-4687}, } @article {pmid30378251, year = {2019}, author = {Fillinger, L and Zhou, Y and Kellermann, C and Griebler, C}, title = {Non-random processes determine the colonization of groundwater sediments by microbial communities in a pristine porous aquifer.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {327-342}, doi = {10.1111/1462-2920.14463}, pmid = {30378251}, issn = {1462-2920}, support = {FKZ 3708 23 200//German Federal Environment Agency (UBA)/ ; FKZ 033W037A-J//German Federal Ministry of Education and Research (BMBF)/ ; }, abstract = {Sediments accommodate the dominating share of groundwater microbiomes, however the processes that govern the assembly and succession of sediment-attached microbial communities in groundwater aquifers are not well understood. To elucidate these processes, we followed the microbial colonization of sterile sediments in in situ microcosms that were exposed to groundwater for almost 1 year at two distant but hydrologically connected sites of a pristine, shallow, porous aquifer. Our results revealed intriguing similarities between the community succession on the newly-colonized sediments and succession patterns previously observed for biofilms in other more dynamic aquatic environments, indicating that the assembly of microbial communities on surfaces may be governed by similar underlying mechanisms across a wide range of different habitats. Null model simulations on spatiotemporally resolved 16S rRNA amplicon sequencing data further indicated selection of specific OTUs rather than random colonization as the main driver of community assembly. A small fraction of persistent OTUs that had established on the sediments during the first 115 days dominated the final communities (68%-85%), suggesting a key role of these early-colonizing organisms, in particular specific genera within the Comamonadaceae and Oxalobacteraceae, for community assembly and succession during the colonization of the sediments. Overall, our study suggests that differences between planktonic and sediment-attached communities often reported for groundwater environments are not the result of purely stochastic events, but that sediment surfaces select for specific groups of microorganisms that assemble over time in a reproducible, non-random way.}, } @article {pmid30377522, year = {2018}, author = {Fritts, SR and Grisham, BA and Cox, RD and Boal, CW and Haukos, DA and McDaniel, P and Hagen, CA and Greene, DU}, title = {Interactive effects of severe drought and grazing on the life history cycle of a bioindicator species.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9550-9562}, pmid = {30377522}, issn = {2045-7758}, abstract = {We used the lesser prairie-chicken (Tympanuchus pallidicinctus), an iconic grouse species that exhibits a boom-bust life history strategy, on the Southern High Plains, USA, as a bioindicator of main and interactive effects of severe drought and grazing. This region experienced the worst drought on record in 2011. We surveyed lesser prairie-chicken leks (i.e., communal breeding grounds) across 12 years that represented 7 years before the 2011 drought (predrought) and 4 years during and following the 2011 drought (postdrought). Grazing was annually managed with the objective of achieving ≤50% utilization of aboveground vegetation biomass. We used lek (n = 49) count data and covariates of weather and managed grazing to: (a) estimate long-term lesser prairie-chicken abundance and compare abundance predrought and postdrought; (b) examine the influence of annual and seasonal drought (modified Palmer drought index), temperature, and precipitation on long-term lesser prairie-chicken survival and recruitment; and (c) assess and compare the influence of grazing on lesser prairie-chicken population predrought and postdrought. Lesser prairie-chicken abundance was nearly seven times greater predrought than postdrought, and population declines were attributed to decreased survival and recruitment. The number of days with temperature >90th percentile had the greatest effect, particularly on recruitment. The population exhibited a substantial bust during 2011 and 2012 without a boom to recover in four postdrought years. Adaptive grazing positively influenced the population predrought, but had no effects postdrought. Results suggest that the severe drought in 2011 may have been beyond the range of environmental conditions to which lesser prairie-chickens, and likely other species, have adapted. Land management practices, such as grazing, should remain adaptive to ensure potential negative influences to all species are avoided. Increasing habitat quantity and quality by reducing habitat loss and fragmentation likely will increase resiliency of the ecosystem and individual species.}, } @article {pmid30377521, year = {2018}, author = {Almojil, D and Cliff, G and Spaet, JLY}, title = {Weak population structure of the Spot-tail shark Carcharhinus sorrah and the Blacktip shark C. limbatus along the coasts of the Arabian Peninsula, Pakistan, and South Africa.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9536-9549}, pmid = {30377521}, issn = {2045-7758}, abstract = {The increase in demand for shark meat and fins has placed shark populations worldwide under high fishing pressure. In the Arabian region, the spot-tail shark Carcharhinus sorrah and the Blacktip shark Carcharhinus limbatus are among the most exploited species. In this study, we investigated the population genetic structure of C. sorrah (n = 327) along the coasts of the Arabian Peninsula and of C. limbatus (n = 525) along the Arabian coasts, Pakistan, and KwaZulu-Natal, South Africa, using microsatellite markers (15 and 11 loci, respectively). Our findings support weak population structure in both species. Carcharhinus sorrah exhibited a fine structure, subdividing the area into three groups. The first group comprises all samples from Bahrain, the second from the UAE and Yemen, and the third from Oman. Similarly, C. limbatus exhibited population subdivision into three groups. The first group, comprising samples from Bahrain and Kuwait, was highly differentiated from the second and third groups, comprising samples from Oman, Pakistan, the UAE, and Yemen; and South Africa and the Saudi Arabian Red Sea, respectively. Population divisions were supported by pairwise FST values and discriminant analysis of principal components (DAPC), but not by STRUCTURE. We suggest that the mostly low but significant pairwise FST values in our study are suggestive of fine population structure, which is possibly attributable to behavioral traits such as residency in C. sorrah and site fidelity and philopatry in C. limbatus. However, for all samples obtained from the northern parts of the Gulf (Bahrain and/or Kuwait) in both species, the higher but significant pairwise FST values could possibly be a result of founder effects during the Tethys Sea closure. Based on DAPC and FST results, we suggest each population to be treated as independent management unit, as conservation concerns emerge.}, } @article {pmid30377520, year = {2018}, author = {Liang, D and He, C and Luo, X and Liu, Y and Goodale, E and Pagani-Núñez, E}, title = {Breath rate of passerines across an urbanization gradient supports the pace-of-life hypothesis and suggests diet-mediated responses to handling stress.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9526-9535}, pmid = {30377520}, issn = {2045-7758}, abstract = {The pace-of-life hypothesis predicts no impact of urbanization on stress responses. Accordingly, several studies have been inconsistent in showing differences in breath rate (BR), a proxy of acute stress responses to handling in passerines, between rural and urban areas. However, this evidence is limited to a single bird species and a limited geographic region (SW Europe). No study addressed whether this pattern is also apparent in other species or regions, such as in tropical environments, or whether it is dependent on the level of diet specialization, given that diet restriction and change influence stress responses. Here, we tested whether there were differences in BR between habitats and diet groups using eight highly diverse passerine assemblages experiencing different levels of anthropogenic disturbance (i.e., natural, rural, and urban locations) in SW China. We predicted that insectivores and herbivores (frugivores, nectarivores, and seed-eating species) would show higher BR than omnivores. We also predicted no differences in BR among habitat types. BR was a moderately repeatable trait, which showed a negative relationship with body mass and a positive relationship with the time of the day. We also recorded a relatively strong phylogenetic bias in the expression of this trait. Confirming our predictions, our results showed no differences in BR among natural, rural, and urban locations. Similarly, within species, there were no differences in BR between rural and urban locations. However, we also found that herbivores showed higher BR than omnivores. Overall, our results provide support to the pace-of-life hypothesis, but suggest acute stress responses can be diet-mediated, which may help to explain the marked decline of specialized trophic guilds around the world in response to anthropogenic disturbance.}, } @article {pmid30377519, year = {2018}, author = {Mobley, KB and Morrongiello, JR and Warr, M and Bray, DJ and Wong, BBM}, title = {Female ornamentation and the fecundity trade-off in a sex-role reversed pipefish.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9516-9525}, pmid = {30377519}, issn = {2045-7758}, abstract = {Sexual ornaments found only in females are a rare occurrence in nature. One explanation for this is that female ornaments are costly to produce and maintain and, therefore, females must trade-off resources related to reproduction to promote ornament expression. Here, we investigate whether a trade-off exists between female ornamentation and fecundity in the sex-role reversed, wide-bodied pipefish, Stigmatopora nigra. We measured two components of the disk-shaped, ventral-striped female ornament, body width, and stripe thickness. After controlling for the influence of body size, we found no evidence of a cost of belly width or stripe thickness on female fecundity. Rather, females that have larger ornaments have higher fecundity and thus accurately advertise their reproductive value to males without incurring a cost to fecundity. We also investigated the relationship between female body size and egg size and found that larger females suffer a slight decrease in egg size and fecundity, although this decrease was independent of female ornamentation. More broadly, considered in light of similar findings in other taxa, lack of an apparent fecundity cost of ornamentation in female pipefish underscores the need to revisit theoretical assumptions concerning the evolution of female ornamentation.}, } @article {pmid30377518, year = {2018}, author = {Matley, JK and Maes, GE and Devloo-Delva, F and Huerlimann, R and Chua, G and Tobin, AJ and Fisk, AT and Simpfendorfer, CA and Heupel, MR}, title = {Integrating complementary methods to improve diet analysis in fishery-targeted species.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9503-9515}, pmid = {30377518}, issn = {2045-7758}, abstract = {Developing efficient, reliable, cost-effective ways to identify diet is required to understand trophic ecology in complex ecosystems and improve food web models. A combination of techniques, each varying in their ability to provide robust, spatially and temporally explicit information can be applied to clarify diet data for ecological research. This study applied an integrative analysis of a fishery-targeted species group-Plectropomus spp. in the central Great Barrier Reef, Australia, by comparing three diet-identification approaches. Visual stomach content analysis provided poor identification with ~14% of stomachs sampled resulting in identification to family or lower. A molecular approach was successful with prey from ~80% of stomachs identified to genus or species, often with several unique prey in a stomach. Stable isotope mixing models utilizing experimentally derived assimilation data, identified similar prey as the molecular technique but at broader temporal scales, particularly when prior diet information was incorporated. Overall, Caesionidae and Pomacentridae were the most abundant prey families (>50% prey contribution) for all Plectropomus spp., highlighting the importance of planktivorous prey. Less abundant prey categories differed among species/color phases indicating possible niche segregation. This study is one of the first to demonstrate the extent of taxonomic resolution provided by molecular techniques, and, like other studies, illustrates that temporal investigations of dietary patterns are more accessible in combination with stable isotopes. The consumption of mainly planktivorous prey within this species group has important implications within coral reef food webs and provides cautionary information regarding the effects that changing resources could have in reef ecosystems.}, } @article {pmid30377517, year = {2018}, author = {Erkosar, B and Yashiro, E and Zajitschek, F and Friberg, U and Maklakov, AA and van der Meer, JR and Kawecki, TJ}, title = {Host diet mediates a negative relationship between abundance and diversity of Drosophila gut microbiota.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9491-9502}, pmid = {30377517}, issn = {2045-7758}, abstract = {Nutrient supply to ecosystems has major effects on ecological diversity, but it is unclear to what degree the shape of this relationship is general versus dependent on the specific environment or community. Although the diet composition in terms of the source or proportions of different nutrient types is known to affect gut microbiota composition, the relationship between the quantity of nutrients supplied and the abundance and diversity of the intestinal microbial community remains to be elucidated. Here, we address this relationship using replicate populations of Drosophila melanogaster maintained over multiple generations on three diets differing in the concentration of yeast (the only source of most nutrients). While a 6.5-fold increase in yeast concentration led to a 100-fold increase in the total abundance of gut microbes, it caused a major decrease in their alpha diversity (by 45-60% depending on the diversity measure). This was accompanied by only minor shifts in the taxonomic affiliation of the most common operational taxonomic units (OTUs). Thus, nutrient concentration in host diet mediates a strong negative relationship between the nutrient abundance and microbial diversity in the Drosophila gut ecosystem.}, } @article {pmid30377516, year = {2018}, author = {van Dijk, KJ and Bricker, E and van Tussenbroek, BI and Waycott, M}, title = {Range-wide population genetic structure of the Caribbean marine angiosperm Thalassia testudinum.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9478-9490}, pmid = {30377516}, issn = {2045-7758}, abstract = {Many marine species have widespread geographic ranges derived from their evolutionary and ecological history particularly their modes of dispersal. Seagrass (marine angiosperm) species have ranges that are unusually widespread, which is not unexpected following recent reviews of reproductive strategies demonstrating the potential for long-distance dispersal combined with longevity through clonality. An exemplar of these dual biological features is turtle grass (Thalassia testudinum) which is an ecologically important species throughout the tropical Atlantic region. Turtle grass has been documented to have long-distance dispersal via floating fruits and also extreme clonality and longevity. We hypothesize that across its range, Thalassia testudinum will have very limited regional population structure due to these characteristics and under typical models of population structure would expect to detect high levels of genetic connectivity. There are very few studies of range-wide genetic connectivity documented for seagrasses or other sessile marine species. This study presents a population genetic dataset that represents a geographic area exceeding 14,000 km2. Population genetic diversity was evaluated from 32 Thalassia testudinum populations sampled across the Caribbean and Gulf of Mexico. Genotypes were based on nine microsatellites, and haplotypes were based on chloroplast DNA sequences. Very limited phylogeographic signal from cpDNA reduced the potential comparative analyses possible. Multiple analytical clustering approaches on population genetic data revealed two significant genetic partitions: (a) the Caribbean and (b) the Gulf of Mexico. Genetic diversity was high (HE = 0.641), and isolation by distance was significant; gene flow and migration estimates across the entire range were however modest, we suggest that the frequency of successful recruitment across the range is uncommon. Thalassia testudinum maintains genetic diversity across its entire distribution range. The genetic split may be explained by genetic drift during recolonization from refugia following relatively recent reduction in available habitat such as the last glacial maxima.}, } @article {pmid30377515, year = {2018}, author = {Oliveira, T and Urra, F and López-Martín, JM and Ballesteros-Duperón, E and Barea-Azcón, JM and Moléon, M and Gil-Sánchez, JM and Alves, PC and Díaz-Ruíz, F and Ferreras, P and Monterroso, P}, title = {Females know better: Sex-biased habitat selection by the European wildcat.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9464-9477}, pmid = {30377515}, issn = {2045-7758}, abstract = {The interactions between animals and their environment vary across species, regions, but also with gender. Sex-specific relations between individuals and the ecosystem may entail different behavioral choices and be expressed through different patterns of habitat use. Regardless, only rarely sex-specific traits are addressed in ecological modeling approaches. The European wildcat (Felis silvestris silvestris) is a species of conservation concern in Europe, with a highly fragmented and declining distribution across most of its range. We assessed sex-specific habitat selection patterns for the European wildcat, at the landscape and home range levels, across its Iberian biogeographic distribution using a multipopulation approach. We developed resource selection functions in a use-availability framework using radio-telemetry data from five wildcat populations. At the landscape level, we observed that, while both genders preferentially established home ranges in areas close to broadleaf forests and far from humanized areas, females selected mid-range elevation areas with some topographic complexity, whereas males used lowland areas. At the home range level, both females and males selected areas dominated by scrublands or broadleaf forests, but habitat features were less important at this level. The strength of association to habitat features was higher for females at both spatial levels, suggesting a tendency to select habitats with higher quality that can grant them enhanced access to shelter and feeding resources. Based on our results, we hypothesize that sex-biased behavioral patterns may contribute to the resilience of wildcats' genetic integrity through influencing the directionality of hybridization with domestic cats. Our study provides information about European wildcats' habitat use in an Iberian context, relevant for the implementation of conservation plans, and highlights the ecological relevance of considering sex-related differences in environmental preferences.}, } @article {pmid30377514, year = {2018}, author = {Mengüllüoğlu, D and Ambarlı, H and Berger, A and Hofer, H}, title = {Foraging ecology of Eurasian lynx populations in southwest Asia: Conservation implications for a diet specialist.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9451-9463}, pmid = {30377514}, issn = {2045-7758}, abstract = {Intraspecific variation in key traits of widespread species can be hard to predict, if populations have been very little studied in most of the distribution range. Asian populations of the Eurasian lynx (Lynx lynx), one of the most widespread felids worldwide, are such a case in point. We investigated the diet of Eurasian lynx from feces collected Mediterranean, mixed forest-steppe, and subalpine ecosystems of Turkey. We studied prey preferences and functional responses using prey densities obtained from Random Encounter Modelling. Our analysis revealed that the main prey was brown hare (Lepus europaeus) in all three areas (78%-99% of biomass consumed) and lynx showed a strong preference for brown hare (Chesson's selectivity index, α = 0.90-0.99). Cannibalism contributed at least 5% in two study areas. The type II functional response of lynx populations in Turkey was similar to the Canada lynx (Lynx canadensis) and daily food intake in grams per lynx matched that of Canada lynx and Iberian lynx (Lynx pardinus), both lagomorph specialists, rather than those of Eurasian lynx from Europe. Therefore, lynx in Turkey may be better described as a lagomorph specialist even though it coexists with ungulate prey. We suggest that ungulate-based foraging ecology of Eurasian lynx in Europe may be a recent adjustment to the availability of high densities of ungulates and cannot be representative for other regions like Turkey. The status of lagomorphs should become an essential component of conservation activities targeted at Eurasian lynx or when using this species as a flagship species for landscape preservation.}, } @article {pmid30377513, year = {2018}, author = {Lin, H and Zhao, Y and Muyidong, N and Tian, K and He, Z and Kong, X and Sun, S and Tian, X}, title = {Secondary compounds of Pinus massoniana alter decomposers' effects on Quercus variabilis litter decomposition.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9439-9450}, pmid = {30377513}, issn = {2045-7758}, abstract = {A major gap to understand the effects of plant secondary compounds on litter decomposition in the brown food web is lack of information about how these secondary compounds modify the activities of soil decomposers. To address this question, we conducted an experiment where aqueous extracts and tannins prepared from Pinus massoniana needles were added to soils collected either from P. massoniana (pine soil) or Quercus variabilis (oak soil). Our objective was to investigate the cascading effects of the two compounds on isopod (Armadillidium vulgare) activity and subsequent change in Q. variabilis litter decomposition. We found that in pine soil, both aqueous extracts and tannins (especially at high concentrations) had positive effects on litter decomposition rates when isopods were present. While without isopods, litter decomposition was enhanced only by high concentrations of aqueous extracts, and tannins had no significant effect on decomposition. In oak soil, high concentrations of aqueous extracts and tannins inhibited litter decomposition and soil microbial biomass, regardless of whether isopods were present or not. Low concentrations of aqueous extracts increased litter decomposition rates and soil microbial biomass in oak soil in the absence of isopods. Based on our results, we suggest that the high concentration of secondary compounds in P. massoniana is a key factor influencing the effects of decomposers on litter decomposition rates, and tannins form a major part of secondary compounds. These funding particularly provide insight into form- and concentration-oriented effects of secondary compounds and promote our understanding of litter decomposition and soil nutrient cycling in forest ecosystem.}, } @article {pmid30377512, year = {2018}, author = {Josefson, AB and Loo, LO and Blomqvist, M and Rolandsson, J}, title = {Substantial changes in the depth distributions of benthic invertebrates in the eastern Kattegat since the 1880s.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9426-9438}, pmid = {30377512}, issn = {2045-7758}, abstract = {Bottom trawling and eutrophication are well known for their impacts on the marine benthic environment in the last decades. Evaluating the effects of these pressures is often restricted to contemporary benthic data, limiting the potential to observe change from an earlier (preimpact) state. In this study, we compared benthic species records from 1884 to 1886 by CGJ Petersen with recent data to investigate how benthic invertebrate species in the eastern Kattegat have changed since preimpact time. The study shows that species turnover between old and recent times was high, ca. 50%, and the species richness in the investigation area was either unchanged or higher in recent times, suggesting no net loss of species. Elements of metacommunity structure analysis of datasets from the 1880s, 1990s, and 2000s revealed a clear change in the depth distribution structure since the 1880s. The system changed from a Quasi-nested/Random pattern unrelated to depth in the 1880s with many species depth ranges over a major part of the studied depth interval, to a Clementsian pattern in recent times strongly positively correlated with depth. Around 30% of the 117 species recorded both in old and in recent times, including most trawling-sensitive species, that is large, semiemergent species, showed a decrease in maximal depth of occurrence from the deeper zone fished today to the shallower unfished zone, with on average 20 m. Concurrently, the species category remaining in the fished zone was dominated by species less sensitive to bottom trawling like infauna polychaetes and small-sized Peracarida crustaceans, most likely with short longevity. The depth interval and magnitude of the changes in depth distribution and the changes in species composition indicate impacts from bottom trawling rather than eutrophication. Furthermore, the high similarity of results from the recent datasets 10 years apart suggests chronic impact keeping the system in an altered state.}, } @article {pmid30377511, year = {2018}, author = {Mutton, TY and Fuller, SJ and Tucker, D and Baker, AM}, title = {Discovered and disappearing? Conservation genetics of a recently named Australian carnivorous marsupial.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9413-9425}, pmid = {30377511}, issn = {2045-7758}, abstract = {Five new species within the Australian carnivorous marsupial genus Antechinus have recently been named, at least two of which are threatened. Important facets of the habitat use and extinction risk of one of these new species, the buff-footed antechinus, A. mysticus, are not well understood. Previous research has suggested that the species utilizes a broad range of inter-connected forest habitats in southeast Queensland (Qld), Australia. Based on this potentially connected habitat, we predicted that A. mysticus should have low population genetic structure, particularly in relation to its congener, the spatially restricted, high altitude, closed-forest A. subtropicus. We genotyped nine microsatellite loci for six populations of A. mysticus, sampled throughout their known range in eastern Australia, and compared them with four proximate populations of A. subtropicus. Surprisingly, genetic structuring among southeast Qld populations of A. mysticus was moderate to high and similar to that between A. subtropicus populations. We postulate that all A. mysticus populations have declined recently (<100 generations), particularly the northernmost southeast Qld population, which may be at risk of extinction. Our results suggest that A. mysticus is limited to a more scattered and fragmented distribution than previously thought and may be in decline. The identification of population decline in this study and recently in other Antechinus suggests the extinction risk of many Australian mammals should be reassessed.}, } @article {pmid30377510, year = {2018}, author = {Doenz, CJ and Bittner, D and Vonlanthen, P and Wagner, CE and Seehausen, O}, title = {Rapid buildup of sympatric species diversity in Alpine whitefish.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9398-9412}, pmid = {30377510}, issn = {2045-7758}, abstract = {Adaptive radiations in postglacial fish offer excellent settings to study the evolutionary mechanisms involved in the rapid buildup of sympatric species diversity from a single lineage. Here, we address this by exploring the genetic and ecological structure of the largest Alpine whitefish radiation known, that of Lakes Brienz and Thun, using microsatellite data of more than 2000 whitefish caught during extensive species-targeted and habitat-randomized fishing campaigns. We find six strongly genetically and ecologically differentiated species, four of which occur in both lakes, and one of which was previously unknown. These four exhibit clines of genetic differentiation that are paralleled in clines of eco-morphological and reproductive niche differentiation, consistent with models of sympatric ecological speciation along environmental gradients. In Lake Thun, we find two additional species, a profundal specialist and a species introduced in the 1930s from another Alpine whitefish radiation. Strong genetic differentiation between this introduced species and all native species of Lake Thun suggests that reproductive isolation can evolve among allopatric whitefish species within 15,000 years and persist in secondary sympatry. Consistent with speciation theory, we find stronger correlations between genetic and ecological differentiation for sympatrically than for allopatrically evolved species.}, } @article {pmid30377509, year = {2018}, author = {Groner, ML and Hoenig, JM and Pradel, R and Choquet, R and Vogelbein, WK and Gauthier, DT and Friedrichs, MAM}, title = {Dermal mycobacteriosis and warming sea surface temperatures are associated with elevated mortality of striped bass in Chesapeake Bay.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9384-9397}, pmid = {30377509}, issn = {2045-7758}, abstract = {Temperature is hypothesized to alter disease dynamics, particularly when species are living at or near their thermal limits. When disease occurs in marine systems, this can go undetected, particularly if the disease is chronic and progresses slowly. As a result, population-level impacts of diseases can be grossly underestimated. Complex migratory patterns, stochasticity in recruitment, and data and knowledge gaps can hinder collection and analysis of data on marine diseases. New tools enabling quantification of disease impacts in marine environments include coupled biogeochemical hydrodynamic models (to hindcast key environmental data), and multievent, multistate mark-recapture (MMSMR) (to quantify the effects of environmental conditions on disease processes and assess population-level impacts). We used MMSMR to quantify disease processes and population impacts in an estuarine population of striped bass (Morone saxatilis) in Chesapeake Bay from 2005 to 2013. Our results supported the hypothesis that mycobacteriosis is chronic, progressive, and, frequently, lethal. Yearly disease incidence in fish age three and above was 89%, suggesting that this disease impacts nearly every adult striped bass. Mortality of diseased fish was high, particularly in severe cases, where it approached 80% in typical years. Severely diseased fish also had a 10-fold higher catchability than healthy fish, which could bias estimates of disease prevalence. For both healthy and diseased fish, mortality increased with the modeled average summer sea surface temperature (SST) at the mouth of the Rappahannock River; in warmer summers (average SST ≥ 29°C), a cohort is predicted to experience >90% mortality in 1 year. Regression of disease signs in mildly and moderately diseased fish was <2%. These results suggest that these fish are living at their maximum thermal tolerance and that this is driving increased disease and mortality. Management of this fishery should account for the effects of temperature and disease on impacted populations.}, } @article {pmid30377508, year = {2018}, author = {Flynn, DJH and Lynch, TP and Barrett, NS and Wong, LSC and Devine, C and Hughes, D}, title = {Gigapixel big data movies provide cost-effective seascape scale direct measurements of open-access coastal human use such as recreational fisheries.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9372-9383}, pmid = {30377508}, issn = {2045-7758}, abstract = {Collecting data on unlicensed open-access coastal activities, such as some types of recreational fishing, has often relied on telephone interviews selected from landline directories. However, this approach is becoming obsolete due to changes in communication technology such as a switch to unlisted mobile phones. Other methods, such as boat ramp interviews, are often impractical due to high labor cost. We trialed an autonomous, ultra-high-resolution photosampling method as a cost effect solution for direct measurements of a recreational fishery. Our sequential photosampling was batched processed using a novel software application to produce "big data" time series movies from a spatial subset of the fishery, and we validated this with a regional bus-route survey and interviews with participants at access points. We also compared labor costs between these two methods. Most trailer boat users were recreational fishers targeting tuna spp. Our camera system closely matched trends in temporal variation from the larger scale regional survey, but as the camera data were at much higher frequency, we could additionally describe strong, daily variability in effort. Peaks were normally associated with weekends, but consecutive weekend tuna fishing competitions led to an anomaly of high effort across the normal weekday lulls. By reducing field time and batch processing imagery, Monthly labor costs for the camera sampling were a quarter of the bus-route survey; and individual camera samples cost 2.5% of bus route samples to obtain. Gigapixel panoramic camera observations of fishing were representative of the temporal variability of regional fishing effort and could be used to develop a cost-efficient index. High-frequency sampling had the added benefit of being more likely to detect abnormal patterns of use. Combinations of remote sensing and on-site interviews may provide a solution to describing highly variable effort in recreational fisheries while also validating activity and catch.}, } @article {pmid30377507, year = {2018}, author = {Nakamura, H and Teshima, K and Tachida, H}, title = {Effects of cyclic changes in population size on neutral genetic diversity.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9362-9371}, pmid = {30377507}, issn = {2045-7758}, abstract = {Recurrent changes in population size are often observed in nature, influencing the efficiency of selection and consequently affecting organismal evolution. Thus, it is important to know whether such changes occurred in the past history of a focal population of evolutionary interests. Here, we focused on cyclic changes in population size and investigated the distributional properties of Tajima's D and its power to distinguish a cyclic change model compared with the standard neutral model, changing the frequency and magnitude of the cyclic change. With very low or very high frequencies of the cycle, the distribution of Tajima's D was similar to that in a constant size population, as demonstrated by previous theoretical works. Otherwise, its mean was negative or positive, and its variance was smaller or larger depending on the time of sampling. The detection rate of the cyclic change against the constancy in size by Tajima's D depended on the sample size, the number of loci, and the time of sampling in addition to the frequency and amplitude of the cycle. Using sequence data of several tens of loci, the detection rate was fairly high if the frequency was intermediate and the sampling was made when population size was large; otherwise, the detection rate was not high. We also found that cyclic change could be discriminated from simple expansion or shrinkage of a population by Tajima's D only if the frequency was in a limited range and the sampling was made when the population was large.}, } @article {pmid30377506, year = {2018}, author = {Voigt, CC and Rehnig, K and Lindecke, O and Pētersons, G}, title = {Migratory bats are attracted by red light but not by warm-white light: Implications for the protection of nocturnal migrants.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9353-9361}, pmid = {30377506}, issn = {2045-7758}, abstract = {The replacement of conventional lighting with energy-saving light emitting diodes (LED) is a worldwide trend, yet its consequences for animals and ecosystems are poorly understood. Strictly nocturnal animals such as bats are particularly sensitive to artificial light at night (ALAN). Past studies have shown that bats, in general, respond to ALAN according to the emitted light color and that migratory bats, in particular, exhibit phototaxis in response to green light. As red and white light is frequently used in outdoor lighting, we asked how migratory bats respond to these wavelength spectra. At a major migration corridor, we recorded the presence of migrating bats based on ultrasonic recorders during 10-min light-on/light-off intervals to red or warm-white LED, interspersed with dark controls. When the red LED was switched on, we observed an increase in flight activity for Pipistrellus pygmaeus and a trend for a higher activity for Pipistrellus nathusii. As the higher flight activity of bats was not associated with increased feeding, we rule out the possibility that bats foraged at the red LED light. Instead, bats may have flown toward the red LED light source. When exposed to warm-white LED, general flight activity at the light source did not increase, yet we observed an increased foraging activity directly at the light source compared to the dark control. Our findings highlight a response of migratory bats toward LED light that was dependent on light color. The most parsimonious explanation for the response to red LED is phototaxis and for the response to warm-white LED foraging. Our findings call for caution in the application of red aviation lighting, particularly at wind turbines, as this light color might attract bats, leading eventually to an increased collision risk of migratory bats at wind turbines.}, } @article {pmid30377505, year = {2018}, author = {Nystrand, M and Cassidy, EJ and Dowling, DK}, title = {The effects of a bacterial challenge on reproductive success of fruit flies evolved under low or high sexual selection.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9341-9352}, pmid = {30377505}, issn = {2045-7758}, abstract = {The capacity of individuals to cope with stress, for example, from pathogen exposure, might decrease with increasing levels of sexual selection, although it remains unclear which sex should be more sensitive. Here, we measured the ability of each sex to maintain high reproductive success following challenges with either heat-killed bacteria or procedural control, across replicate populations of Drosophila melanogaster evolved under either high or low levels of sexual selection. Our experiment was run across four separate sampling blocks. We found an interaction between bacterial treatment, sexual selection treatment, and sampling block on female reproductive success. Specifically, and only in the fourth block, we observed that bacterial-challenged females that had evolved under high sexual selection, exhibited lower reproductive success than bacterial-challenged females that had evolved under low sexual selection. Furthermore, we could trace this block-specific effect to a reduction in viscosity of the ovipositioning substrate in the fourth block, in which females laid around 50% more eggs than in previous blocks. In contrast, patterns of male reproductive success were consistent across blocks. Males that evolved under high sexual selection exhibited higher reproductive success than their low-selection counterparts, regardless of whether they were subjected to a bacterial challenge or not. Our results are consistent with the prediction that heightened sexual selection will invoke male-specific evolutionary increases in reproductive fitness. Furthermore, our findings suggest that females might pay fitness costs when exposed to high levels of sexual selection, but that these costs may lie cryptic, and only be revealed under certain environmental contexts.}, } @article {pmid30377504, year = {2018}, author = {Zheng, Y and Hu, J and Zeng, X}, title = {Examining the interglacial high-elevation refugia scenario in East Asian subtropical mountain systems with the frog species Leptobrachium liui.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9326-9340}, pmid = {30377504}, issn = {2045-7758}, abstract = {The effects of Quaternary climatic oscillations on the distributions of organisms in different parts of the world are not equally well understood, limiting the ability to understand the determinants of biodiversity. Compared with the mountain regions in southern Europe and southwestern North America, such effects on high-elevation species in the East Asian subtropical mountain systems located in southern and southeastern China have seldom been addressed. In this study, using Leptobrachium liui (Megophryidae), we made one of the earliest attempts to examine the interglacial high-elevation refugia scenario in these Asian mountains. Based on our current understanding of the study system, we formulated a hypothesis that these frogs of western origin were distributed more widely and continuously during glacial phases, allowing eastward dispersal, and that they are currently isolated in interglacial refugia at higher elevations. Microsatellite data and mitochondrial and nuclear sequence data were obtained with extensive sampling followed by the synthesis of phylogeographic and population genetic analyses and modeling of the species distribution. The analyses revealed a sequential eastward divergence of microsatellite clusters and gene lineages accompanied by a decline in genetic diversity. Molecular dating estimates revealed divergence events in the Pleistocene, and a reduction in local populations was inferred to have occurred at a time comparable to the end of the last glacial. Strong genetic isolation by distance reflecting a more continuous historical distribution was detected. Furthermore, environmental niche models inferred a wide planar distribution during the last glacial maximum, providing further support for the hypothesis.}, } @article {pmid30377503, year = {2018}, author = {Yan, Z and Teng, M and He, W and Wang, Y and Yang, J and Wang, P}, title = {Improving conservation effectiveness of nature reserve for golden snub-nosed monkey, a niche-based approach.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9315-9325}, pmid = {30377503}, issn = {2045-7758}, abstract = {Reserve selections are often opportunistic rather than strategic and coordinated, and consequently, many reserves are ineffective to achieve their intended goals of conservation. Here, we assessed the conservation effectiveness of a reserve for the golden snub-nosed monkeys (Rhinopithecus roxellana) with a niche-based approach. We assessed habitat usage of the monkeys in Shennongjia Nature Reserve (SNR) and attributes of 14 environmental variables that could potentially affect the monkeys' habitat use. Spatial distribution of potentially suitable habitat for the monkeys was then modeled with Maxent, a niche-based model, and conservation effectiveness of SNR was assessed by comparing the current boundary of the reserve with the spatial distribution of the modeled potential habitat and the current habitat area of the monkeys. Only 59% of the habitat area and 61% of the predicted potential habitat area were under the protection of SNR. To improve conservation effectiveness of SNR, we proposed that the current SNR be enlarged by 270 km2. The enlarged reserve would encompass 100% of the existing habitat area plus 89% of the predicted potential habitat area. Using the niche-based approach, we were able to integrate habitat usage data of the target species with that of remote sensing to identify areas potentially suitable as habitat for the species. This information can be used not only for improving conservation effectiveness of existing reserves but also for the effective planning and designing of new reserves.}, } @article {pmid30377502, year = {2018}, author = {Krauss, SL and Roberts, DG and Phillips, RD and Edwards, C}, title = {Effectiveness of camera traps for quantifying daytime and nighttime visitation by vertebrate pollinators.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9304-9314}, pmid = {30377502}, issn = {2045-7758}, abstract = {Identification of pollen vectors is a fundamental objective of pollination biology. The foraging and social behavior of these pollinators has profound effects on plant mating, making quantification of their behavior critical for understanding the ecological and evolutionary consequences of different pollinators for the plants they visit. However, accurate quantification of visitation may be problematic, especially for shy animals and/or when the temporal and spatial scale of observation desired is large. Sophisticated heat- and movement-triggered motion-sensor cameras ("camera trapping") provide new, underutilized tools to address these challenges. However, to date, there has been no rigorous evaluation of the sampling considerations needed for using camera trapping in pollination research.We measured the effectiveness of camera trapping for identifying vertebrate visitors and quantifying their visitation rates and foraging behavior on Banksia menziesii (Proteaceae). Multiple still cameras (Reconyx HC 500) and a video camera (Little Acorn LTL5210A) were deployed.From 2,753 recorded visits by vertebrates, we identified five species of nectarivorous honeyeater (Meliphagidae) and the honey possum (Tarsipedidae), with significant variation in the species composition of visitors among inflorescences. Species of floral visitor showed significant variation in their time of peak activity, duration of visits, and numbers of flowers probed per visit. Where multiple cameras were deployed on individual inflorescences, effectiveness of individual still cameras varied from 15% to 86% of all recorded visits. Methodological issues and solutions, and the future uses of camera traps in pollination biology, are discussed. Conclusions and wider implications: Motion-triggered cameras are promising tools for the quantification of vertebrate visitation and some aspects of behavior on flowers. However, researchers need to be mindful of the variation in effectiveness of individual camera traps in detecting animals. Pollinator studies using camera traps are in their infancy, and the full potential of this developing technology is yet to be realized.}, } @article {pmid30377501, year = {2018}, author = {Orlova-Bienkowskaja, MJ and Bieńkowski, AO}, title = {Modeling long-distance dispersal of emerald ash borer in European Russia and prognosis of spread of this pest to neighboring countries within next 5 years.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9295-9304}, pmid = {30377501}, issn = {2045-7758}, abstract = {Aim: To develop an approach to model the spatial dynamics of emerald ash borer Agrilus planipennis (Coleoptera: Buprestidae) in European Russia. This tree-killing pest was detected in Moscow 15 years ago and began to spread, posing a threat to ashes all over Europe. The aim was to determine its probable current range and to evaluate the probability of its dispersal to neighboring countries within the next 5 years.

Location: Cities and transport hubs of European Russia and neighboring countries. Ash trees in this region occur mainly in urban plantations and along highways.

Methods: Pairwise distances between all locations were used as the main parameter determining the probability of pest spread. For each location, the probability of detection of A. planipennis was calculated using three simulation recurrent models of long-distance dispersal. Parametrization was made by comparison with results of surveys in 2003-2015. Field data on the range of A. planipennis in 2016-2017 were mapped and used for model verification. A prognosis of spread of the pest by 2022 was made.

Results: A model based on fat-tailed kernel corresponds to both negative and positive results of surveys. According to the model, the current range is likely to be restricted to Russia, but probability of detection of the pest in the east of Belarus, Ukraine, Estonia, Latvia, and Lithuania by 2022 is 15%-40%.

Main conclusions: The forestry services of neighboring countries probably have about 5 years to prepare for the invasion of this pest, but regular surveys are necessary, since the pest can appear at any time. The case considered shows that the simple approach based on a fat-tailed kernel and just one parameter-pairwise distance between cities-can be used for modeling long-distance dispersal of alien pests of urban plantations.}, } @article {pmid30377500, year = {2018}, author = {Moran, RL and Zhou, M and Catchen, JM and Fuller, RC}, title = {Hybridization and postzygotic isolation promote reinforcement of male mating preferences in a diverse group of fishes with traditional sex roles.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9282-9294}, pmid = {30377500}, issn = {2045-7758}, abstract = {Behavioral isolation is thought to arise early in speciation due to differential sexual and/or natural selection favoring different preferences and traits in different lineages. Instead, behavioral isolation can arise due to reinforcement favoring traits and preferences that prevent maladaptive hybridization. In darters, female preference for male coloration has been hypothesized to drive speciation, because behavioral isolation evolves before F1 inviability. However, as with many long-lived organisms, the fitness of second-generation hybrids has not been assessed because raising animals to adulthood in the laboratory is challenging. Of late, reinforcement of male preferences has been implicated in darters because male preference for conspecific females is high in sympatry but absent in allopatry in multiple species pairs. The hypothesis that reinforcement accounts for behavioral isolation in sympatry assumes that hybridization and postzygotic isolation are present. Here, we used genomic and morphological data to demonstrate that hybridization is ongoing between orangethroat and rainbow darters and used hybrids collected from nature to measure postzygotic barriers across two hybrid generations. We observed sex ratio distortion in adult F1s and a dramatic reduction in backcross survival. Our findings indicate that selection to avoid hybridization promotes the evolution of male-driven behavioral isolation via reinforcement in this system.}, } @article {pmid30377499, year = {2018}, author = {Meichtry-Stier, KS and Duplain, J and Lanz, M and Lugrin, B and Birrer, S}, title = {The importance of size, location, and vegetation composition of perennial fallows for farmland birds.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9270-9281}, pmid = {30377499}, issn = {2045-7758}, abstract = {Across Europe, patches of un-cropped land (field margins, fallows, etc.) have been established and managed as part of agri-environment schemes (AES) to counteract the decrease in farmland biodiversity. Various studies demonstrate a positive impact of such un-cropped land on different taxa. However, there is potential to further improve the efficiency of fallow options for farmland birds. In a long-term monitoring, 12 breeding farmland bird species and sizes of perennial fallows were recorded from 1992 to 2015 in a 6.1 km2 area in Switzerland. Furthermore, habitat composition and fallow characteristics were mapped in 2012. We calculated population trends, analyzed habitat associations and revealed the impact of fallow habitat characteristics on territory density. The proportion of fallows in the study site increased from 1.4% (1992) to 8.5% (2012). Population trends of six of 12 censused species increased significantly over the same time, four species showed no trend and trends of two species decreased. Seven species were analyzed in more detail, for five of them fallows were overrepresented around their territory center points compared to arable fields and grassland. The overall territory density of these five species was higher in small fallows which were not placed next to a wood and which held bramble rubus spp., shrubs and the tall-growing forb goldenrod (Solidago canadensis and S. gigantea). Our study confirms that perennial fallows are a highly suitable option to support different farmland birds in arable landscapes. Yet, we recommend optimizing fallows through careful site selection and management, such that they are not established on shady locations and are structurally diverse by allowing brambles, shrubs, and tall-growing forbs to occur. We suggest adapting the Swiss AES in this regard. Biodiversity-related advisory services available for farmers could increase the probability that fallow options are implemented and managed properly for targeted species.}, } @article {pmid30377498, year = {2018}, author = {Thibault, M and Masse, F and Pujapujane, A and Lannuzel, G and Bordez, L and Potter, MA and Fogliani, B and Vidal, É and Brescia, F}, title = {"Liaisons dangereuses": The invasive red-vented bulbul (Pycnonotus cafer), a disperser of exotic plant species in New Caledonia.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9259-9269}, pmid = {30377498}, issn = {2045-7758}, abstract = {The biodiversity hotspot of New Caledonia hosts high levels of endemism (74% of flora) that is threatened increasingly by climate change, habitat reduction, and invasive species. The fruit-eating red-vented bulbul (Pycnonotus cafer) is currently invading the main island of the archipelago, and its recent dispersal out of urbanized habitats raises questions about its potential to disperse noxious plant seeds along urban corridors and beyond. Indeed, the red-vented bulbul is considered a vector of several introduced plant species in its alien range including Miconia calvescens, Lantana camara, and Schinus terebinthifolius. We conducted a quantitative assessment of the bulbul's fruits consumption by analyzing the gut contents of shot birds. We estimated gut passage times for four species of fruit found in gut contents (S. terebinthifolius, Myrtastrum rufopunctatum, Passiflora suberosa, and Ficus prolixa) and tested the effects of bird digestion on seed germination rates for two species. Finally, we monitored the movements of individual VHF radio-tagged red-vented bulbuls. All of the consumed fruit species we identified here have red fleshy diaspore, including fruit of the shrub M. rufopunctatum that occurred frequently (9.6%) in bulbul gut samples. Median gut passage times were short (15-41 min), corresponding to short-distance seed transportation (77-92 m). The effect of gut passage was positive for the germination of the invasive S. terebinthifolius and negative for the endemic M. rufopunctatum, suggesting a potential bias in the contribution to the dispersal toward alien species. This study provides the first integrated assessment of mechanisms involved in the seed dispersal effectiveness of this high-concern invasive bird species that is expected to face similar plant communities in most of its alien range in tropical islands. More generally, our results enhance knowledge of synergies between non-native frugivores and plant species dispersal.}, } @article {pmid30377497, year = {2018}, author = {Nykänen, M and Dillane, E and Englund, A and Foote, AD and Ingram, SN and Louis, M and Mirimin, L and Oudejans, M and Rogan, E}, title = {Quantifying dispersal between marine protected areas by a highly mobile species, the bottlenose dolphin, Tursiops truncatus.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9241-9258}, pmid = {30377497}, issn = {2045-7758}, abstract = {The functioning of marine protected areas (MPAs) designated for marine megafauna has been criticized due to the high mobility and dispersal potential of these taxa. However, dispersal within a network of small MPAs can be beneficial as connectivity can result in increased effective population size, maintain genetic diversity, and increase robustness to ecological and environmental changes making populations less susceptible to stochastic genetic and demographic effects (i.e., Allee effect). Here, we use both genetic and photo-identification methods to quantify gene flow and demographic dispersal between MPAs of a highly mobile marine mammal, the bottlenose dolphin Tursiops truncatus. We identify three populations in the waters of western Ireland, two of which have largely nonoverlapping core coastal home ranges and are each strongly spatially associated with specific MPAs. We find high site fidelity of individuals within each of these two coastal populations to their respective MPA. We also find low levels of demographic dispersal between the populations, but it remains unclear whether any new gametes are exchanged between populations through these migrants (genetic dispersal). The population sampled in the Shannon Estuary has a low estimated effective population size and appears to be genetically isolated. The second coastal population, sampled outside of the Shannon, may be demographically and genetically connected to other coastal subpopulations around the coastal waters of the UK. We therefore recommend that the methods applied here should be used on a broader geographically sampled dataset to better assess this connectivity.}, } @article {pmid30377496, year = {2018}, author = {Aylward, ML and Sullivan, AP and Perry, GH and Johnson, SE and Louis, EE}, title = {An environmental DNA sampling method for aye-ayes from their feeding traces.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9229-9240}, pmid = {30377496}, issn = {2045-7758}, abstract = {Noninvasive sampling is an important development in population genetic monitoring of wild animals. Particularly, the collection of environmental DNA (eDNA) which can be collected without needing to encounter the target animal facilitates the genetic analysis of endangered species. One method that has been applied to these sample types is target capture and enrichment which overcomes the issue of high proportions of exogenous (nonhost) DNA from these lower quality samples. We tested whether target capture of mitochondrial DNA from sampled feeding traces of the aye-aye, an endangered lemur species would yield mitochondrial DNA sequences for population genetic monitoring. We sampled gnawed wood where aye-ayes excavate wood-boring insect larvae from trees. We designed RNA probes complementary to the aye-aye's mitochondrial genome and used these to isolate aye-aye DNA from other nontarget DNA in these samples. We successfully retrieved six near-complete mitochondrial genomes from two sites within the aye-aye's geographic range that had not been sampled previously. Our method demonstrates the application of next-generation molecular techniques to species of conservation concern. This method can likely be applied to alternative foraged remains to sample endangered species other than aye-ayes.}, } @article {pmid30377495, year = {2018}, author = {Molina-García, L and Pérez, JM and Sarasa, M and Ureña-Gutiérrez, B and Espinosa, J and Azorit, C}, title = {HPLC-QTOF method for quantifying 11-ketoetiocholanolone, a cortisol metabolite, in ruminants' feces: Optimization and validation.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9218-9228}, pmid = {30377495}, issn = {2045-7758}, abstract = {Studies of animal ecology can benefit from a quantified understanding of eco-physiological processes and, in particular, of the physiological responses in free-ranging animals to potential stressors. The determination of fecal cortisol metabolites as a noninvasive method for monitoring stress has proved to be a powerful tool. High-performance liquid chromatography coupled with tandem mass spectrometry (HPLC-MS/MS) has emerged as the most accurate method for avoiding problems related to the nonspecificity of immunoassays. In this study, we optimize and validate a reliable method using HPLC-MS/MS for quantifying 11-ketoetiocholanolone (11-k), a representative fecal cortisol metabolite in ruminants. An appropriate extraction and purification procedure was developed taking into account the complex nature of feces. The final extract obtained was then analyzed with HPLC-MS/MS using a quadrupole-time-of-fly (QTOF) tandem mass spectrometer with an electrospray ionization interface operating in positive mode, which allowed an unequivocal determination of the metabolite due to its accurate mass capabilities. After rigorous optimization of both sample extraction and the HPLC-QTOF parameters, making use of feces from free-ranging Iberian ibex, ideal conditions were established. Matrix-matched standards were used to calibrate the method. The limit of detection and quantification was 13- and 40- ng/g, respectively. The validation of the method was performed with recoveries in the range of 85-110%, a figure much higher than the 60% obtained with the previous extraction methods used in our laboratory, and with relative standard deviations (RSDs) no higher than 15% for the complete analytical procedure, including extraction and analysis. The time required for the fecal 11-k analysis was greatly reduced in comparison with the previous work carried out in our laboratory. This is the first time that QTOF mass detection coupled with HPLC has been validated for 11-k quantification in feces from free-ranging ruminants such as Iberian ibex. Given the high selectivity and sensitivity attained, our method could become a useful tool for noninvasive stress quantification in ruminants.}, } @article {pmid30377494, year = {2018}, author = {Nuche-Pascual, MT and Lazo, JP and Ruiz-Cooley, RI and Herzka, SZ}, title = {Amino acid-specific δ15N trophic enrichment factors in fish fed with formulated diets varying in protein quantity and quality.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9192-9217}, pmid = {30377494}, issn = {2045-7758}, abstract = {Compound-specific isotope analysis (CSIA) of amino acids (AAs) in consumer tissues is a developing technique with wide-ranging applications for identifying nitrogen (N) sources and estimating animal trophic level. Controlled experiments are essential for determining which dietary conditions influence variability in N stable isotopes (δ15N) trophic enrichment factors in bulk tissue (TEFbulk) and AAs (TEFAA). To date, however, studies have not independently evaluated the effect of protein quantity and quality (digestibility) on TEFs, complicating the application of AA-δ15N values for estimating trophic levels. We conducted a 98-d feeding experiment using five formulated isoenergetic feeds prepared with a high-quality protein source to evaluate the effect of protein quantity and quality on TEFs of liver and muscle tissues of juvenile Pacific yellowtail (Seriola lalandi), a carnivorous fish species. We decreased protein digestibility using well-established protocols that do not change AA profiles. Growth rates were higher in diets with higher protein content, and isotopic equilibrium was reached for both fish tissues and all treatments. Protein quantity and quality influenced isotope discrimination depending on tissue type and AA. In liver tissue, bulk TEFs showed a limited but significant relationship with protein quality, but did not differ with protein quantity or quality in muscle. None of the pre-established source AAs (Lys, Met, Phe, and Gly) TEFs varied significantly with protein quantity or quality in liver tissue. However, in muscle tissue, TEFPhe increased significantly with protein content and decreased in response to reduced digestibility, indicating it may not serve as proxy for baseline isotopic values used to calculate trophic level. Among trophic AAs, TEFLeu decreased significantly with increasing protein quantity in liver tissue, while both Leu and Ile TEFs decreased with lower protein digestibility in muscle tissue. Our results indicate that CSIA-AA in liver tissue provides more robust source and trophic AA-δ15N values than in muscle.}, } @article {pmid30377493, year = {2018}, author = {Robinson, CV and Garcia de Leaniz, C and James, J and Cable, J and Orozco-terWengel, P and Consuegra, S}, title = {Genetic diversity and parasite facilitated establishment of the invasive signal crayfish (Pacifastacus leniusculus) in Great Britain.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9181-9191}, pmid = {30377493}, issn = {2045-7758}, abstract = {Successful establishment of non-native species is strongly influenced, among other factors, by the genetic variation of founding populations, which can be enhanced by multiple introductions through admixture. Coexisting pathogens can also facilitate the establishment of non-native species by detrimentally impacting on the native fauna acting as novel weapons. The signal crayfish (Pacifastacus leniusculus) is a highly invasive species, which has caused mass declines of native crayfish in Europe through displacement and transmission of the oomycete Aphanomyces astaci (crayfish plague), which is typically lethal to native European crayfish. However, whether Aphanomyces astaci may have facilitated the invasion of the signal crayfish is not known. We estimated the genetic diversity at microsatellite DNA loci, effective population size, and potential origins of seven infected and noninfected signal crayfish populations in Europe and one founder population in North America. Approximate Bayesian computation analysis and population structuring suggested multiple host introductions from diverse source populations, as well as higher heterozygosity among infected than uninfected populations, which could reflect a fitness advantage. Low effective population size, moderate heterozygosity, and lack of isolation by distance suggest that some invasive signal crayfish populations may not be fully established or that their genetic diversity may have been reduced by eradication attempts.}, } @article {pmid30377492, year = {2018}, author = {Edwards, S and Fischer, M and Wachter, B and Melzheimer, J}, title = {Coping with intrasexual behavioral differences: Capture-recapture abundance estimation of male cheetah.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9171-9180}, pmid = {30377492}, issn = {2045-7758}, abstract = {Population estimates are a fundamental requirement of ecology and conservation. While capture-recapture models are an established method for producing such estimates, their assumption of homogeneous capture probabilities is problematic given that heterogeneity in individual capture probability is inherent to most species. Such variation must be accounted for by abundance models; otherwise, biased estimates are risked.Here, we investigate the performance of four types of heterogeneity models for estimating abundance of male cheetah Acinonyx jubatus, a species with two distinct spatial tactics of territorial and nonterritorial (floater) males. The differences in spatial movements of territory holders and floaters are expected to result in intrasexual heterogeneous capture probabilities. Four heterogeneity models were used to model male abundance at five territories in central Namibia; (a) a spatial tactic model, (b) a finite mixture model, both run in program MARK, (c) a floater-only model, and (d) a heterogeneity Mh model, both run in the program CAPTURE. Camera trap data of cheetah, taken at frequently visited marking trees, were used to derive true abundance. Model results were compared to the true abundance to assess the accuracy of estimates.Only models (a), (b), and (c) were able to consistently produce accurate results. Mixture models do not require prior knowledge regarding spatial tactic of males, which might not always be available. Therefore, we recommend such models as the preferred model type for cheetahs.Results highlight the potential for mixture models in overcoming the challenges of capture probability heterogeneity and in particular their use with species where intrasexual behavioral differences exist.}, } @article {pmid30377491, year = {2018}, author = {Griffen, BD}, title = {Reproductive skipping as an optimal life history strategy in the southern elephant seal, Mirounga leonina.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9158-9170}, pmid = {30377491}, issn = {2045-7758}, abstract = {Intermittent breeding by which organisms skip some current reproductive opportunities in order to enhance future reproductive success is a common life history trade-off among long-lived, iteroparous species. The southern elephant seal Mirounga leonina engages in intermediate breeding when body condition is low. While it is anticipated that this strategy may increase the lifetime reproductive output of this species, the conditions under which reproductive skipping are predicted to occur are not clear. Here I develop a dynamic state variable model based on published data that examines when southern elephant seals are predicted to optimally skip reproduction in order to maximize lifetime reproductive output as a function of current body mass, maternal age, and survivorship. I demonstrate that the optimal reproductive strategy for this species can include reproductive skipping, and that the conditions where this is optimal depend on patterns of mass-dependent adult female survival. I further show that intermittent breeding can increase lifetime reproductive output, and that the magnitude of this benefit increases with the ability of individual animals to replenish depleted body mass through foraging. Finally, I show that when the environment is variable and foraging is reduced in bad years, the benefit of adopting an optimal strategy that includes reproductive skipping increases asymptotically with the frequency of bad years. These results highlight the importance of characterizing the pattern of adult survival in this species, as well as the need to identify other factors that may influence the prevalence and benefits of reproductive skipping.}, } @article {pmid30377490, year = {2018}, author = {Han, CS and Jablonski, PG}, title = {Increased female resistance to mating promotes the effect of mechanical constraints on latency to pair.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9152-9157}, pmid = {30377490}, issn = {2045-7758}, abstract = {Size-assortative mating, defined as a positive linear association of body size between members of mating pairs, can arise from mechanical constraints on pairing efficiency, particularly when mating success is affected by males' mate-grasping force. In this context, female resistance is predicted to have an important role in changing the threshold force necessary for males to hold females, thereby contributing to the effect of mechanical constraints. Thus, increased female resistance is expected to increase the paring success of an optimally sized male relative to the female body size (sexual size ratio = male body size/female body size = 0.86), which leads to positive size-assortative mating. However, very little is known about the extent to which female resistance affects mechanical constraints on mate grasping. Here, using the water strider Gerris gracilicornis (Hemiptera: Gerridae), we tested whether the level of female resistance affected the relationship between the sexual size ratio and latency to pair. We found that optimally sized males mated sooner than other males when females resisted a male's mating attempts. When females did not resist, an effect of sexual size ratio on latency to pair was not found. Our results thus imply that increased female resistance to male mating attempts may strengthen the pattern of size-assortative mating. We provide clear empirical evidence that female resistance to mating influences the effect of mechanical constraints on size-assortative mating under sexual conflict. This result further suggests that patterns of size-assortative mating can be altered by a variety of ecological circumstances that change female resistance to mating in many other animal species under sexual conflict.}, } @article {pmid30377489, year = {2018}, author = {Chapin, KJ and Winkler, DE and Wiencek, P and Agnarsson, I}, title = {Island biogeography and ecological modeling of the amblypygid Phrynus marginemaculatus in the Florida Keys archipelago.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9139-9151}, pmid = {30377489}, issn = {2045-7758}, abstract = {Aim: The biogeography of terrestrial organisms across the Florida Keys archipelago is poorly understood. We used population genetics and spatioecological modeling of the Amblypygi Phrynus marginemaculatus to understand the genetic structure and metapopulation dynamics of Keys populations that are otherwise isolated by human development and ocean.

Location: The Florida Keys archipelago and mainland Florida.

Methods: We sequenced a 1,238 bp fragment of mtDNA for 103 individuals of P. marginemaculatus from 13 sites in the Florida Keys and South Florida, binned into four regions. We used population genetic analyses to understand the population structure of the species throughout its US range. Furthermore, we used ecological modeling with climate, habitat, and human development data to develop habitat suitability estimates for the species.

Results: We found clear genetic structure between localities. The Lower Keys, in particular, support populations separate from those in other regions studied. Ecological modeling and genetic analyses showed the highest habitat suitability and genetic isolation in the Lower Keys, but urban development across the species range has resulted in the loss of most historical habitat.

Main conclusions: A mainland-metapopulation model best fits P. marginemaculatus gene flow patterns in the Florida Keys and mainland. Ocean currents likely play a role in metapopulation dynamics and gene flow for terrestrial Keys species like P. marginemaculatus, and genetic patterns also matched patterns consistent with geologic history. Suitable habitat, however, is limited and under threat of human destruction. The few remaining pockets of the most suitable habitat tend to occur in parks and protected areas. We argue that conservation efforts for this species and others in the terrestrial Florida Keys would benefit from a deeper understanding of the population genetic structure and ecology of the archipelago.}, } @article {pmid30377488, year = {2018}, author = {Penn, HJ and Crist, TO}, title = {From dispersal to predation: A global synthesis of ant-seed interactions.}, journal = {Ecology and evolution}, volume = {8}, number = {18}, pages = {9122-9138}, pmid = {30377488}, issn = {2045-7758}, abstract = {Ant-seed interactions take several forms, including dispersal, predation, and parasitism, whereby ants consume seed appendages without dispersal of seeds. We hypothesized that these interaction outcomes could be predicted by ant and plant traits and habitat, with outcomes falling along a gradient of cost and benefit to the plant. To test this hypothesis, we conducted a global literature review and classified over 6,000 pairs of ant-seed interactions from 753 studies across six continents. Linear models showed that seed and ant size, habitat, and dispersal syndrome were the most consistent predictors. Predation was less likely than parasitism and seed dispersal among myrmecochorous plants. A classification tree of the predicted outcomes from linear models revealed that dispersal and predation formed distinct categories based on habitat, ant size, and dispersal mode, with parasitism outcomes forming a distinct subgroup of predation based on seed size and shape. Multiple correspondence analysis indicated some combinations of ant genera and plant families were strongly associated with particular outcomes, whereas other ant-seed combinations were much more variable. Taken together, these results demonstrate that ant and plant traits are important overall predictors of potential seed fates in different habitat types.}, } @article {pmid30377476, year = {2018}, author = {Corwin, LA and Dolan, EL and Graham, MJ and Hanauer, DI and Pelaez, N}, title = {The Need to Be Sure About CUREs: Discovery and Relevance as Critical Elements of CUREs for Nonmajors.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377476}, issn = {1935-7877}, } @article {pmid30377475, year = {2018}, author = {Howell, ME and van Dijk, K and Booth, CS and Helikar, T and Couch, BA and Roston, RL}, title = {Visualizing the Invisible: A Guide to Designing, Printing, and Incorporating Dynamic 3D Molecular Models to Teach Structure-Function Relationships.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377475}, issn = {1935-7877}, } @article {pmid30377474, year = {2018}, author = {Genné-Bacon, EA and Bascom-Slack, CA}, title = {The PARE Project: A Short Course-Based Research Project for National Surveillance of Antibiotic-Resistant Microbes in Environmental Samples.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377474}, issn = {1935-7877}, abstract = {Course-based research experiences (CREs) have been proposed as an inclusive model to expose all students, including those at institutions without a strong research infrastructure, to research at an early stage. Converting an entire semester-long course can be time consuming for instructors and expensive for institutions, so we have developed a short CRE that can be implemented in a variety of life science course types. The Prevalence of Antibiotic Resistance in the Environment (PARE) project uses common microbiology methods and equipment to engage students in nationwide surveillance of environmental soil samples to document the prevalence of antibiotic-resistant bacteria. The project has been implemented at institutions ranging from community colleges to doctoral-granting institutions in 30 states plus Puerto Rico. Programmatic feedback was obtained from instructors over three iterations, and revisions were made based on this feedback. Student learning was measured by pre/post assessment in a subset of institutions. Outcomes indicate that students made significant gains in the project learning goals. Journal of Microbiology & Biology Education.}, } @article {pmid30377473, year = {2018}, author = {Govindan, B}, title = {Bacterial Survivor: An Interactive Game that Combats Misconceptions about Antibiotic Resistance.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377473}, issn = {1935-7877}, } @article {pmid30377472, year = {2018}, author = {Killpack, TL and Fulmer, SM}, title = {Development of a Tool to Assess Interrelated Experimental Design in Introductory Biology.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377472}, issn = {1935-7877}, abstract = {Designing experiments and applying the process of science are core competencies for many introductory courses and course-based undergraduate research experiences (CUREs). However, experimental design is a complex process that challenges many introductory students. We describe the development of a tool to assess interrelated experimental design (TIED) in an introductory biology lab course. We describe the interrater reliability of the tool, its effectiveness in detecting variability and growth in experimental-design skills, and its adaptability for use in various contexts. The final tool contained five components, each with multiple criteria in the form of a checklist such that a high-quality response-in which students align the different components of their experimental design-satisfies all criteria. The tool showed excellent interrater reliability and captured the full range of introductory-student skill levels, with few students hitting the assessment ceiling or floor. The scoring tool detected growth in student skills from the beginning to the end of the semester, with significant differences between pre- and post-assessment scores for the Total Score and for the Data Collection and Observations component scores. This authentic assessment task and scoring tool provide meaningful feedback to instructors about the strengths, gaps, and growth in introductory students' experimental-design skills and can be scored reliably by multiple instructors. The TIED can also be adapted to a number of experimental-design prompts and learning objectives, and therefore can be useful for a variety of introductory courses and CUREs.}, } @article {pmid30377471, year = {2018}, author = {Kolokithas, A and Calderón, O}, title = {A How-To Guide on Bringing Undergraduate Research to Community and Technical Colleges.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377471}, issn = {1935-7877}, abstract = {Increasing the interest and participation of students in STEM is a priority for colleges, universities, and the nation as a whole. As new generations of students embark in training and in learning novel technologies to deal with the challenges of emerging infectious diseases, crop and food production, and the development of new and better sustainable alternatives in the face of a changing environment on our planet, we must also evolve our approach to teaching and learning. One strategy that may be found helpful as students face the challenges ahead is to instill inquiry and problem-solving skills as part of their education as early as possible, whether they pursue a technical career or a graduate college degree. Although many existing technical and community colleges were built with the purpose of teaching a specific skill to supply the demand of a workforce in developing industries, the disappearance of some industries and evolution of others call for a different approach to teaching and learning at this level of education. Here, we present two alternatives to teaching and learning, by implementing scientific research that can result in the development of more holistic students, who are ready to tackle the challenges encountered as they graduate and enter the workforce. Journal of Microbiology & Biology Education.}, } @article {pmid30377470, year = {2018}, author = {Meyer, CA and Hall, H and Heise, N and Kaminski, K and Ivie, KR and Clapp, TR}, title = {A Systematic Approach to Teaching Case Studies and Solving Novel Problems.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377470}, issn = {1935-7877}, abstract = {Both research and practical experience in education support the use of case studies in the classroom to engage students and develop critical thinking skills. In particular, working through case studies in scientific disciplines encourages students to incorporate knowledge from a variety of backgrounds and apply a breadth of information. While it is recognized that critical thinking is important for student success in professional school and future careers, a specific strategy to tackle a novel problem is lacking in student training. We have developed a four-step systematic approach to solving case studies that improves student confidence and provides them with a definitive road map that is useful when solving any novel problem, both in and out of the classroom. This approach encourages students to define unfamiliar terms, create a timeline, describe the systems involved, and identify any unique features. This method allows students to solve complex problems by organizing and applying information in a logical progression. We have incorporated case studies in anatomy and neuroanatomy courses and are confident that this systematic approach will translate well to courses in various scientific disciplines.}, } @article {pmid30377469, year = {2018}, author = {Gubbels, JAA and Vitiello, SP}, title = {Creating and Teaching Science Lessons in K-12 Schools Increases Undergraduate Students' Science Identity.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377469}, issn = {1935-7877}, abstract = {Success and persistence in the life sciences is influenced by a student's self-efficacy, sense of belonging, and science identity. It has already been demonstrated that outreach experiences and service learning by graduate students in K-12 schools aid in the graduate students' confidence and intrinsic satisfaction. Others have shown the importance of engaging scientists in outreach activities, both for the benefit of the K-12 student and as a way to engage scientists with the community. We predicted it would also be beneficial for undergraduates to engage in service-learning activities during their coursework because working with K-12 students would solidify their scientific identity and sense of belonging while deepening their understanding of the course content. Consequently, we implemented service projects in our upper-level molecular biology and human physiology courses at a primarily undergraduate institution that focuses on five core values: Christian, Liberal Arts, Excellence, Community, and Service. Outcomes such as the undergraduate students' value of service, confidence in their knowledge of course content, ability to create effective lesson plans, and science identity were measured using anonymous surveys. Overall, students reported that they highly valued and enjoyed this unique experience. This type of activity could be used to increase future scientists' awareness of synergistic activities such as academic service and of the joy found in such activities. Future plans include measuring the effects on the participating high school and elementary school students and visiting schools with a high proportion of students from underserved populations.}, } @article {pmid30377468, year = {2018}, author = {Hageman, J and Krikken, AM}, title = {Single-Step Gene Knockout of the SUC2 Gene in Saccharomyces cerevisiae : A Laboratory Exercise for Undergraduate Students.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377468}, issn = {1935-7877}, } @article {pmid30377467, year = {2018}, author = {Winters, JM and Wang, H and Duwel, LE and Spudich, EA and Stanford, JS}, title = {Developing a Backup Plan: Implementing a Career-Planning Course for Undergraduate Biology Majors.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377467}, issn = {1935-7877}, abstract = {Career-planning courses are known to be effective career interventions for undergraduates, but their effect on developing alternate career plans was previously unknown. Forming alternate career plans increases the likelihood that students have viable career options available to them upon graduation because it encourages students to realistically consider multiple possibilities. Here we describe a one-term career-planning course developed in the context of an undergraduate biology curriculum. We assessed whether this course promoted development of primary and alternate career plans using a pre/post survey. We saw a significant increase in the percentage of students indicating they had plans aimed at achieving primary (increase of 37%) and alternate (increase of 48%) career goals from the beginning to the end of the course. Preliminary outcomes suggest that implementation of this course correlates with an increase in the percentage of students who indicate they have a job after graduation (increase of 16%). This type of course could be implemented in many other contexts to support career development in diverse fields.}, } @article {pmid30377466, year = {2018}, author = {Pape-Zambito, DA and Mostrom, AM}, title = {Improving Teaching through Triadic Course Alignment.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {3}, pages = {}, pmid = {30377466}, issn = {1935-7877}, abstract = {Triadic alignment is a pedagogical technique that instructors can use to improve their teaching and students' learning. It involves offering the course learning objectives, teaching and learning activities, and assessments at the same cognitive process level. Though it represents a best practice, few instructors have assessed the efficacy of triadic alignment. Previous research has demonstrated that General Biology courses are commonly misaligned relative to the objectives and assessments. However, little emphasis has been placed on assessing the teaching and learning activities as the third component of triadic alignment. In this article, we describe how a General Biology course was initially misaligned, the process that was taken to align it, and the improved student outcomes that resulted from triadic alignment. We expand our discussion to include types of misalignment and the benefits of triadic alignment for both the students and the faculty member.}, } @article {pmid30377333, year = {2018}, author = {}, title = {Brazil's new president adds to global threat to science.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {5-6}, doi = {10.1038/d41586-018-07236-w}, pmid = {30377333}, issn = {1476-4687}, mesh = {Brazil ; Environmental Policy/*legislation & jurisprudence ; *Federal Government ; *Politics ; Science/*legislation & jurisprudence ; }, } @article {pmid30377332, year = {2018}, author = {}, title = {US proposal for defining gender has no basis in science.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {5}, doi = {10.1038/d41586-018-07238-8}, pmid = {30377332}, issn = {1476-4687}, mesh = {*Anus, Imperforate ; Female ; *Hernia, Umbilical ; Humans ; Infant, Newborn ; Politics ; Science ; Sex Determination Analysis ; United States ; *Urogenital Abnormalities ; }, } @article {pmid30377331, year = {2018}, author = {Dance, A}, title = {Hungarian association wins prize for promoting participation of women in science.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {147-148}, doi = {10.1038/d41586-018-07199-y}, pmid = {30377331}, issn = {1476-4687}, mesh = {*Awards and Prizes ; Female ; Humans ; Hungary ; *Nobel Prize ; }, } @article {pmid30377330, year = {2018}, author = {Dance, A}, title = {Meet the space researcher smoothing the path for women in science across Africa.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {148}, doi = {10.1038/d41586-018-07198-z}, pmid = {30377330}, issn = {1476-4687}, } @article {pmid30377329, year = {2018}, author = {Perkel, JM}, title = {Web service makes big data available to neuroscientists.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {143}, doi = {10.1038/d41586-018-07195-2}, pmid = {30377329}, issn = {1476-4687}, } @article {pmid30377328, year = {2018}, author = {Del Bello, L}, title = {Mothballed Mount Everest climate observatory could reopen by early next year.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {17-18}, doi = {10.1038/d41586-018-06846-8}, pmid = {30377328}, issn = {1476-4687}, mesh = {Air Pollution/adverse effects/analysis ; *Altitude ; Atmosphere/chemistry ; *Climate ; Human Activities ; Italy ; Nepal ; Research/economics/*instrumentation/*trends ; }, } @article {pmid30377327, year = {2018}, author = {Warren, M}, title = {'Why didn't we think to do this earlier?' Chemists thrilled by speedy atomic structures.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {16-17}, doi = {10.1038/d41586-018-07213-3}, pmid = {30377327}, issn = {1476-4687}, mesh = {Chemistry, Organic/*methods ; Crystallography, X-Ray ; *Electrons ; Pharmaceutical Preparations/*chemistry ; Proteins/chemistry ; Time Factors ; }, } @article {pmid30377326, year = {2018}, author = {Castelvecchi, D}, title = {Europe shows first cards in €1-billion quantum bet.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {14-15}, doi = {10.1038/d41586-018-07216-0}, pmid = {30377326}, issn = {1476-4687}, } @article {pmid30377325, year = {2018}, author = {}, title = {Crystal-clear movies show the bustling activity inside a cell.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {8}, doi = {10.1038/d41586-018-07176-5}, pmid = {30377325}, issn = {1476-4687}, mesh = {Endoplasmic Reticulum/metabolism ; Fluorescent Dyes/analysis ; Imaging, Three-Dimensional/methods ; *Microscopy, Video ; Mitochondria/metabolism ; Molecular Imaging/*methods ; Organelles/*metabolism ; *Video Recording ; }, } @article {pmid30377324, year = {2018}, author = {}, title = {Space crews' grey matter shrivels during long stays in orbit.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {9}, doi = {10.1038/d41586-018-07163-w}, pmid = {30377324}, issn = {1476-4687}, mesh = {*Astronauts ; Cerebrospinal Fluid ; Gray Matter/*anatomy & histology/growth & development/*pathology ; Humans ; Organ Size ; *Space Flight ; Time Factors ; White Matter/anatomy & histology/pathology ; }, } @article {pmid30377323, year = {2018}, author = {}, title = {How tar making helped Vikings launch their fearsome fleets.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {9}, doi = {10.1038/d41586-018-07159-6}, pmid = {30377323}, issn = {1476-4687}, mesh = {History, Ancient ; Manufacturing Industry/*history ; Ships/*history/*instrumentation ; Wood/chemistry ; }, } @article {pmid30377322, year = {2018}, author = {Witze, A}, title = {Mars scientists edge closer to solving methane mystery.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {18-19}, doi = {10.1038/d41586-018-07177-4}, pmid = {30377322}, issn = {1476-4687}, } @article {pmid30377321, year = {2018}, author = {Maxmen, A}, title = {Rare genetic sequences illuminate early humans' history in Africa.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {13-14}, doi = {10.1038/d41586-018-07164-9}, pmid = {30377321}, issn = {1476-4687}, } @article {pmid30377320, year = {2018}, author = {}, title = {Salmon-hurling scientists enrich an ecosystem.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {9}, doi = {10.1038/d41586-018-07142-1}, pmid = {30377320}, issn = {1476-4687}, mesh = {Alaska ; Animals ; Diet/veterinary ; Fertilizers/*analysis ; *Food Chain ; Picea/*growth & development/*metabolism ; Rivers ; Salmon/*metabolism ; Ursidae/physiology ; }, } @article {pmid30377319, year = {2018}, author = {Wight, AJ}, title = {Strict EU ruling on gene-edited crops squeezes science.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {15-16}, doi = {10.1038/d41586-018-07166-7}, pmid = {30377319}, issn = {1476-4687}, mesh = {Agriculture/economics/*legislation & jurisprudence ; Animals ; Belgium ; Brazil ; Breeding/legislation & jurisprudence ; CRISPR-Cas Systems/genetics ; Crops, Agricultural/economics/*genetics ; *European Union ; Evaluation Studies as Topic ; France ; Gene Editing/*legislation & jurisprudence ; Humans ; Plants, Genetically Modified/*genetics ; }, } @article {pmid30377318, year = {2018}, author = {}, title = {Teleportation over a 6-kilometre cable, courtesy of quantum powers.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {9}, doi = {10.1038/d41586-018-07137-y}, pmid = {30377318}, issn = {1476-4687}, } @article {pmid30377317, year = {2018}, author = {}, title = {A deep-space camera that can spot a volcano's puffs.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {8}, doi = {10.1038/d41586-018-07127-0}, pmid = {30377317}, issn = {1476-4687}, } @article {pmid30377316, year = {2018}, author = {}, title = {Enzyme inspired by primeval molecules shows its superpowers.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {8}, doi = {10.1038/d41586-018-07134-1}, pmid = {30377316}, issn = {1476-4687}, mesh = {Animals ; Biocatalysis/drug effects ; Cytochrome P-450 Enzyme System/*chemistry/*metabolism ; Enzyme Stability/drug effects ; *Evolution, Molecular ; Solvents/chemistry/pharmacology ; Temperature ; }, } @article {pmid30377313, year = {2018}, author = {Kong, L and Sochacki, KA and Wang, H and Fang, S and Canagarajah, B and Kehr, AD and Rice, WJ and Strub, MP and Taraska, JW and Hinshaw, JE}, title = {Author Correction: Cryo-EM of the dynamin polymer assembled on lipid membrane.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {E6}, doi = {10.1038/s41586-018-0612-2}, pmid = {30377313}, issn = {1476-4687}, abstract = {In Figs. 2b and 3d of this Letter, the labels 'Dynamin 1' and 'Overlay' were inadvertently swapped. This has been corrected online.}, } @article {pmid30377312, year = {2018}, author = {Wisotzki, L and Bacon, R and Brinchmann, J and Cantalupo, S and Richter, P and Schaye, J and Schmidt, KB and Urrutia, T and Weilbacher, PM and Akhlaghi, M and Bouché, N and Contini, T and Guiderdoni, B and Herenz, EC and Inami, H and Kerutt, J and Leclercq, F and Marino, RA and Maseda, M and Monreal-Ibero, A and Nanayakkara, T and Richard, J and Saust, R and Steinmetz, M and Wendt, M}, title = {Author Correction: Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {E31}, doi = {10.1038/s41586-018-0664-3}, pmid = {30377312}, issn = {1476-4687}, abstract = {Change history: In this Letter, author M. Akhlaghi should be associated with affiliation (2) rather than (3). This error has been corrected online.}, } @article {pmid30377311, year = {2018}, author = {Roy Chowdhury, R and Vallania, F and Yang, Q and Lopez Angel, CJ and Darboe, F and Penn-Nicholson, A and Rozot, V and Nemes, E and Malherbe, ST and Ronacher, K and Walzl, G and Hanekom, W and Davis, MM and Winter, J and Chen, X and Scriba, TJ and Khatri, P and Chien, YH}, title = {Author Correction: A multi-cohort study of the immune factors associated with M. tuberculosis infection outcomes.}, journal = {Nature}, volume = {564}, number = {7734}, pages = {E5}, doi = {10.1038/s41586-018-0635-8}, pmid = {30377311}, issn = {1476-4687}, support = {R21 AI127128/AI/NIAID NIH HHS/United States ; }, abstract = {The spelling of author Qianting Yang was corrected; the affiliation of author Stephanus T. Malherbe was corrected; and graphs in Fig. 4b and c were corrected owing to reanalysis of the data into the correct timed intervals.}, } @article {pmid30377273, year = {2018}, author = {Kawakami, M and Mustachio, LM and Zheng, L and Chen, Y and Rodriguez-Canales, J and Mino, B and Kurie, JM and Roszik, J and Villalobos, PA and Thu, KL and Silvester, J and Cescon, DW and Wistuba, II and Mak, TW and Liu, X and Dmitrovsky, E}, title = {Reply to Oegema et al.: CFI-400945 and Polo-like kinase 4 inhibition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10810-E10811}, pmid = {30377273}, issn = {1091-6490}, support = {R01 CA190722/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Indazoles ; *Indoles ; Lung Neoplasms ; Polyploidy ; }, } @article {pmid30377272, year = {2018}, author = {Oegema, K and Davis, RL and Lara-Gonzalez, P and Desai, A and Shiau, AK}, title = {CFI-400945 is not a selective cellular PLK4 inhibitor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10808-E10809}, pmid = {30377272}, issn = {1091-6490}, support = {R01 GM074207/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Indazoles ; *Indoles ; Lung Neoplasms ; Polyploidy ; Protein-Serine-Threonine Kinases ; }, } @article {pmid30377271, year = {2018}, author = {Liu, Y and McGuire, AF and Lou, HY and Li, TL and Tok, JB and Cui, B and Bao, Z}, title = {Soft conductive micropillar electrode arrays for biologically relevant electrophysiological recording.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11718-11723}, pmid = {30377271}, issn = {1091-6490}, support = {R01 GM125737/GM/NIGMS NIH HHS/United States ; }, mesh = {Action Potentials/physiology ; Animals ; Cell Culture Techniques ; Elastic Modulus ; Electric Conductivity ; Electric Stimulation/*instrumentation ; Electrophysiological Phenomena/physiology ; Equipment Design/*instrumentation/methods ; Hydrogels/chemistry/metabolism ; Iridium ; Mice ; Microelectrodes ; Myocytes, Cardiac/physiology ; Neurons/physiology ; Signal-To-Noise Ratio ; }, abstract = {Multielectrode arrays (MEAs) are essential tools in neural and cardiac research as they provide a means for noninvasive, multiplexed recording of extracellular field potentials with high temporal resolution. To date, the mechanical properties of the electrode material, e.g., its Young's modulus, have not been taken into consideration in most MEA designs leaving hard materials as the default choice due to their established fabrication processes. However, the cell-electrode interface is known to significantly affect some aspects of the cell's behavior. In this paper, we describe the fabrication of a soft 3D micropillar electrode array. Using this array, we proceed to successfully record action potentials from monolayer cell cultures. Specifically, our conductive hydrogel micropillar electrode showed improved signal amplitude and signal-to-noise ratio, compared with conventional hard iridium oxide micropillar electrodes of the same diameter. Taken together, our fabricated soft micropillar electrode array will provide a tissue-like Young's modulus and thus a relevant mechanical microenvironment to fundamental cardiac and neural studies.}, } @article {pmid30377270, year = {2018}, author = {Li, Y and Junge, JA and Arnesano, C and Gross, GG and Miner, JH and Moats, R and Roberts, RW and Arnold, DB and Fraser, SE}, title = {Discs large 1 controls daughter-cell polarity after cytokinesis in vertebrate morphogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10859-E10868}, pmid = {30377270}, issn = {1091-6490}, mesh = {Anaphase ; Animals ; Cartilage/metabolism/physiology ; Cell Cycle ; Cell Polarity/*physiology ; Chick Embryo ; Chondrocytes/metabolism ; Cytokinesis/*physiology ; Discs Large Homolog 1 Protein/*metabolism/physiology ; Embryonic Development ; Fluorescence Resonance Energy Transfer/methods ; HEK293 Cells ; Humans ; Metaphase ; Mice ; Mice, Knockout ; Microscopy, Fluorescence/methods ; Mitosis/physiology ; Morphogenesis/physiology ; Vertebrates/metabolism ; }, abstract = {Vertebrate embryogenesis and organogenesis are driven by cell biological processes, ranging from mitosis and migration to changes in cell size and polarity, but their control and causal relationships are not fully defined. Here, we use the developing limb skeleton to better define the relationships between mitosis and cell polarity. We combine protein-tagging and -perturbation reagents with advanced in vivo imaging to assess the role of Discs large 1 (Dlg1), a membrane-associated scaffolding protein, in mediating the spatiotemporal relationship between cytokinesis and cell polarity. Our results reveal that Dlg1 is enriched at the midbody during cytokinesis and that its multimerization is essential for the normal polarity of daughter cells. Defects in this process alter tissue dimensions without impacting other cellular processes. Our results extend the conventional view that division orientation is established at metaphase and anaphase and suggest that multiple mechanisms act at distinct phases of the cell cycle to transmit cell polarity. The approach employed can be used in other systems, as it offers a robust means to follow and to eliminate protein function and extends the Phasor approach for studying in vivo protein interactions by frequency-domain fluorescence lifetime imaging microscopy of Förster resonance energy transfer (FLIM-FRET) to organotypic explant culture.}, } @article {pmid30377269, year = {2018}, author = {Jin, I and Udo, H and Kassabov, S and Kosmidis, S and Zhu, H and Kandel, ER and Hawkins, RD}, title = {Anterograde and retrograde signaling by an Aplysia neurotrophin forms a transsynaptic functional unit.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10951-E10960}, pmid = {30377269}, issn = {1091-6490}, support = {R01 NS083690/NS/NINDS NIH HHS/United States ; //Howard Hughes Medical Institute/International ; }, mesh = {Animals ; Aplysia/*metabolism ; Cells, Cultured ; Excitatory Postsynaptic Potentials ; Feedback, Physiological ; Motor Neurons/metabolism ; Neuronal Plasticity ; Neurons, Afferent/metabolism ; Prepulse Inhibition ; Presynaptic Terminals/metabolism ; Sensory Receptor Cells/metabolism ; Serotonin/metabolism ; Signal Transduction ; Synapses/*metabolism ; }, abstract = {Whereas short-term synaptic plasticity is often either pre- or postsynaptic, intermediate- and long-term plasticity generally require coordinated pre- and postsynaptic mechanisms. Thus, the transition from presynaptic short-term facilitation (STF) to intermediate-term facilitation (ITF) induced by 5HT at Aplysia sensory-to-motor neuron synapses requires the recruitment of postsynaptic mechanisms and activation of protein synthesis in both neurons. In the companion paper to this report, we found that presynaptic autocrine signaling by an Aplysia neurotrophin (ApNT) forms a positive feedback loop that drives the synapses from STF to ITF. Here we report that ApNT also acts through both anterograde and retrograde signaling to form a transsynaptic positive feedback loop that orchestrates cellular functions in both the presynaptic and postsynaptic neurons during the induction of ITF. These two feedback loops activate protein synthesis in each synaptic compartment, which in both cases depends on signaling from the other synaptic compartment. These results suggest that the pre- and postsynaptic compartments act as one functional unit during the consolidation of learning-related facilitation induced by 5HT.}, } @article {pmid30377268, year = {2018}, author = {Holzwart, E and Huerta, AI and Glöckner, N and Garnelo Gómez, B and Wanke, F and Augustin, S and Askani, JC and Schürholz, AK and Harter, K and Wolf, S}, title = {BRI1 controls vascular cell fate in the Arabidopsis root through RLP44 and phytosulfokine signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11838-11843}, pmid = {30377268}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/*metabolism/*physiology ; Brassinosteroids/metabolism ; Cell Differentiation/physiology ; Peptide Hormones/metabolism ; Phosphorylation ; Plant Proteins/metabolism ; Plant Roots/metabolism ; Plants, Genetically Modified/metabolism ; Protein Binding ; Protein Kinases/*metabolism/*physiology ; Protein-Serine-Threonine Kinases/metabolism ; Receptors, Cell Surface/metabolism ; Signal Transduction/physiology ; }, abstract = {Multicellularity arose independently in plants and animals, but invariably requires a robust determination and maintenance of cell fate that is adaptive to the environment. This is exemplified by the highly specialized water- and nutrient-conducting cells of the plant vasculature, the organization of which is already prepatterned close to the stem-cell niche, but can be modified according to extrinsic cues. Here, we show that the hormone receptor BRASSINOSTEROID INSENSITIVE 1 (BRI1) is required for root vascular cell-fate maintenance, as BRI1 mutants show ectopic xylem in procambial position. However, this phenotype seems unrelated to canonical brassinosteroid signaling outputs. Instead, BRI1 is required for the expression and function of its interacting partner RECEPTOR-LIKE PROTEIN 44 (RLP44), which, in turn, associates with the receptor for the peptide hormone phytosulfokine (PSK). We show that PSK signaling is required for the maintenance of procambial cell identity and quantitatively controlled by RLP44, which promotes complex formation between the PSK receptor and its coreceptor. Mimicking the loss of RLP44, PSK-related mutants show ectopic xylem in the position of the procambium, whereas rlp44 is rescued by exogenous PSK. Based on these findings, we propose that RLP44 controls cell fate by connecting BRI1 and PSK signaling, providing a mechanistic framework for the dynamic balancing of signaling mediated by the plethora of plant receptor-like kinases at the plasma membrane.}, } @article {pmid30377267, year = {2018}, author = {Wall, JS and Williams, AD and Foster, JS and Richey, T and Stuckey, A and Macy, S and Wooliver, C and Campagna, SR and Tague, ED and Farmer, AT and Lands, RH and Martin, EB and Heidel, RE and Kennel, SJ}, title = {Bifunctional amyloid-reactive peptide promotes binding of antibody 11-1F4 to diverse amyloid types and enhances therapeutic efficacy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10839-E10848}, pmid = {30377267}, issn = {1091-6490}, support = {R01 DK110038/DK/NIDDK NIH HHS/United States ; }, mesh = {Amyloid/metabolism ; Amyloidogenic Proteins/metabolism ; Amyloidosis/*metabolism/*therapy ; Animals ; Antibodies, Bispecific/immunology ; Antibodies, Monoclonal/immunology/*physiology ; Cadaver ; Epitopes/metabolism ; Humans ; Immunoglobulin Light Chains/immunology ; Mice ; Peptides/metabolism ; Positron Emission Tomography Computed Tomography ; Protein Binding ; Serum Amyloid A Protein/metabolism ; Tissue Distribution ; Treatment Outcome ; }, abstract = {Amyloidosis is a malignant pathology associated with the formation of proteinaceous amyloid fibrils that deposit in organs and tissues, leading to dysfunction and severe morbidity. More than 25 proteins have been identified as components of amyloid, but the most common form of systemic amyloidosis is associated with the deposition of amyloid composed of Ig light chains (AL). Clinical management of amyloidosis focuses on reducing synthesis of the amyloid precursor protein. However, recently, passive immunotherapy using amyloid fibril-reactive antibodies, such as 11-1F4, to remove amyloid from organs has been shown to be effective at restoring organ function in patients with AL amyloidosis. However, 11-1F4 does not bind amyloid in all AL patients, as evidenced by PET/CT imaging, nor does it efficiently bind the many other forms of amyloid. To enhance the reactivity and expand the utility of the 11-1F4 mAb as an amyloid immunotherapeutic, we have developed a pretargeting "peptope" comprising a multiamyloid-reactive peptide, p5+14, fused to a high-affinity peptide epitope recognized by 11-1F4. The peptope, known as p66, bound the 11-1F4 mAb in vitro with subnanomolar efficiency, exhibited multiamyloid reactivity in vitro and, using tissue biodistribution and SPECT imaging, colocalized with amyloid deposits in a mouse model of systemic serum amyloid A amyloidosis. Pretreatment with the peptope induced 11-1F4 mAb accumulation in serum amyloid A deposits in vivo and enhanced 11-1F4-mediated dissolution of a human AL amyloid extract implanted in mice.}, } @article {pmid30377266, year = {2018}, author = {Wu, G and Ruben, MD and Schmidt, RE and Francey, LJ and Smith, DF and Anafi, RC and Hughey, JJ and Tasseff, R and Sherrill, JD and Oblong, JE and Mills, KJ and Hogenesch, JB}, title = {Population-level rhythms in human skin with implications for circadian medicine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12313-12318}, pmid = {30377266}, issn = {1091-6490}, support = {R01 HG005220/HG/NHGRI NIH HHS/United States ; R01 NS054794/NS/NINDS NIH HHS/United States ; R21 NS101983/NS/NINDS NIH HHS/United States ; R35 GM124685/GM/NIGMS NIH HHS/United States ; }, abstract = {Skin is the largest organ in the body and serves important barrier, regulatory, and sensory functions. The epidermal layer shows rhythmic physiological responses to daily environmental variation (e.g., DNA repair). We investigated the role of the circadian clock in the transcriptional regulation of epidermis using a hybrid experimental design, in which a limited set of human subjects (n = 20) were sampled throughout the 24-h cycle and a larger population (n = 219) were sampled once. We found a robust circadian oscillator in human epidermis at the population level using pairwise correlations of clock and clock-associated genes in 298 epidermis samples. We then used CYCLOPS to reconstruct the temporal order of all samples, and identified hundreds of rhythmically expressed genes at the population level in human epidermis. We compared these results with published time-series skin data from mice and found a strong concordance in circadian phase across species for both transcripts and pathways. Furthermore, like blood, epidermis is readily accessible and a potential source of biomarkers. Using ZeitZeiger, we identified a biomarker set for human epidermis that is capable of reporting circadian phase to within 3 hours from a single sample. In summary, we show rhythms in human epidermis that persist at the population scale and describe a path to develop robust single-sample circadian biomarkers.}, } @article {pmid30377265, year = {2018}, author = {Kim, H and Kim, D and Choi, SA and Kim, CR and Oh, SK and Pyo, KE and Kim, J and Lee, SH and Yoon, JB and Zhang, Y and Baek, SH}, title = {KDM3A histone demethylase functions as an essential factor for activation of JAK2-STAT3 signaling pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11766-11771}, pmid = {30377265}, issn = {1091-6490}, mesh = {Epigenesis, Genetic ; HEK293 Cells/metabolism ; HeLa Cells ; Histones/metabolism ; Humans ; Interleukin-6/metabolism ; Janus Kinase 2/metabolism ; Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism ; Phosphorylation ; Protein-Tyrosine Kinases/metabolism ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Transcriptional Activation ; }, abstract = {Janus tyrosine kinase 2 (JAK2)-signal transducer and activator of transcription 3 (STAT3) signaling pathway is essential for modulating cellular development, differentiation, and homeostasis. Thus, dysregulation of JAK2-STAT3 signaling pathway is frequently associated with human malignancies. Here, we provide evidence that lysine-specific demethylase 3A (KDM3A) functions as an essential epigenetic enzyme for the activation of JAK2-STAT3 signaling pathway. KDM3A is tyrosine-phosphorylated by JAK2 in the nucleus and functions as a STAT3-dependent transcriptional coactivator. JAK2-KDM3A signaling cascade induced by IL-6 leads to alteration of histone H3K9 methylation as a predominant epigenetic event, thereby providing the functional and mechanistic link between activation of JAK2-STAT3 signaling pathway and its epigenetic control. Together, our findings demonstrate that inhibition of KDM3A phosphorylation could be a potent therapeutic strategy to control oncogenic effect of JAK2-STAT3 signaling pathway.}, } @article {pmid30377263, year = {2018}, author = {Beans, C}, title = {Inner Workings: Can robots make good teammates?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11106-11108}, doi = {10.1073/pnas.1814453115}, pmid = {30377263}, issn = {1091-6490}, mesh = {Cooperative Behavior ; Humans ; Robotics/*methods ; Work ; }, } @article {pmid30376988, year = {2018}, author = {Boulton, RA and Zuk, M and Shuker, DM}, title = {An Inconvenient Truth: The Unconsidered Benefits of Convenience Polyandry.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {904-915}, doi = {10.1016/j.tree.2018.10.002}, pmid = {30376988}, issn = {1872-8383}, abstract = {Polyandry, or multiple mating by females with different males, is commonplace. One explanation is that females engage in convenience polyandry, mating multiple times to reduce the costs of sexual harassment. Although the logic underlying convenience polyandry is clear, and harassment often seems to influence mating outcomes, it has not been subjected to as thorough theoretical or empirical attention as other explanations for polyandry. We re-examine here convenience polyandry in the light of new studies demonstrating previously unconsidered benefits of polyandry. We suggest that true convenience polyandry is likely to be a fleeting phenomenon, even though it can profoundly shape mating-system evolution via potential feedback loops between resistance to males and the costs and benefits of mating.}, } @article {pmid30376898, year = {2018}, author = {Leiby, JS and McCormick, K and Sherrill-Mix, S and Clarke, EL and Kessler, LR and Taylor, LJ and Hofstaedter, CE and Roche, AM and Mattei, LM and Bittinger, K and Elovitz, MA and Leite, R and Parry, S and Bushman, FD}, title = {Lack of detection of a human placenta microbiome in samples from preterm and term deliveries.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {196}, pmid = {30376898}, issn = {2049-2618}, support = {P30 AI045008//National Institute of Allergy and Infectious Diseases/ ; T32 AI007632//National Institute of Allergy and Infectious Diseases/ ; T32 AI007324//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: Historically, the human womb has been thought to be sterile in healthy pregnancies, but this idea has been challenged by recent studies using DNA sequence-based methods, which have suggested that the womb is colonized with bacteria. For example, analysis of DNA from placenta samples yielded small proportions of microbial sequences which were proposed to represent normal bacterial colonization. However, an analysis by our group showed no distinction between background negative controls and placenta samples. Also supporting the idea that the womb is sterile is the observation that germ-free mammals can be generated by sterile delivery of neonates into a sterile isolator, after which neonates remain germ-free, which would seem to provide strong data in support of sterility of the womb.

RESULTS: To probe this further and to investigate possible placental colonization associated with spontaneous preterm birth, we carried out another study comparing microbiota in placenta samples from 20 term and 20 spontaneous preterm deliveries. Both 16S rRNA marker gene sequencing and shotgun metagenomic sequencing were used to characterize placenta and control samples. We first quantified absolute amounts of bacterial 16S rRNA gene sequences using 16S rRNA gene quantitative PCR (qPCR). As in our previous study, levels were found to be low in the placenta samples and indistinguishable from negative controls. Analysis by DNA sequencing did not yield a placenta microbiome distinct from negative controls, either using marker gene sequencing as in our previous work, or with shotgun metagenomic sequencing. Several types of artifacts, including erroneous read classifications and barcode misattribution, needed to be identified and removed from the data to clarify this point.

CONCLUSIONS: Our findings do not support the existence of a consistent placental microbiome, in either placenta from term deliveries or spontaneous preterm births.}, } @article {pmid30376890, year = {2018}, author = {Ingersoll, B and Straiton, D and Casagrande, K and Pickard, K}, title = {Community providers' intentions to use a parent-mediated intervention for children with ASD following training: an application of the theory of planned behavior.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {777}, pmid = {30376890}, issn = {1756-0500}, abstract = {OBJECTIVES: The theory of planned behavior (TPB) suggests that attitudes, subjective norms, and perceived behavioral control influence intentions to perform a behavior, and that intentions predict behavior. The present studies examined whether the TPB is applicable to community providers' use of a parent-mediated intervention for children with autism spectrum disorder (ASD) following introductory training and whether TPB constructs can be modified with training.

RESULTS: Study 1 demonstrated that community providers' intentions to use the intervention post-training predicted their use of the intervention 6 months later [X2(1) = 8.03, p = .005]. Study 2 found that provider education (β = .23, t = 2.27, p = .025), attitudes (β = .21, t = 2.09, p = .039), and perceived behavioral control (β = .21, t = 2.15, p = .035) were all unique predictors of intentions. There was a significant increase in providers' ratings of subjective norms (Z = - 2.46, p = .014) and perceived behavioral control (Z = - 7.36, p < .001) from pre- to post-training. Attitudes towards parent-mediated interventions were highly favorable pre-training and did not significantly increase. Results expand on previous findings and demonstrate the applicability of attitudes and perceived behavioral control in understanding community providers' use of evidence-based practices for children with ASD.}, } @article {pmid30376882, year = {2018}, author = {Alemu, G and Mama, M and Siraj, M}, title = {Bacterial contamination of vegetables sold in Arba Minch Town, Southern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {775}, pmid = {30376882}, issn = {1756-0500}, abstract = {OBJECTIVE: Unhygienically handled fruits and vegetables which are usually consumed in raw serve to transmit various infectious diseases. Bacteria are among the common vegetable contaminants. However, the species of contaminants and rate of contamination depends on various environmental and human factors. Hence, a cross-sectional study was conducted to assess the level of bacterial contamination and associated factors among vegetables marketed in Arba Minch town from January to March, 2018. A structured questionnaire was used to collect data regarding factors associated with bacterial contamination of vegetables. Selected vegetables were purchased and processed for examination of bacterial contamination by standard culture technique following standard protocols. All data were analyzed using SPSS version 20.0.

RESULTS: A total of 347 vegetable samples were examined, of which 169 (48.7%) were positive for bacteria contamination. Cabbage (71.9%) was the most frequently contaminated vegetable. E. coli (31.4%) was the most frequent contaminant detected. Type of vegetables (p = 0.000) and market place (p = 0.039) show significant association with bacterial contamination. Bacterial contamination rate in the present study was significantly considerable. Therefore we recommend for the local health office to continuously monitor the contamination status of raw edible vegetables and take respective measures.}, } @article {pmid30376878, year = {2018}, author = {Shinozawa, E and Kawamura, M}, title = {Anti-thrombotic effect of a factor Xa inhibitor TAK-442 in a rabbit model of arteriovenous shunt thrombosis stimulated with tissue factor.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {776}, pmid = {30376878}, issn = {1756-0500}, abstract = {OBJECTIVE: Arterial thrombosis is triggered by tissue factor, which is a transmembrane glycoprotein can be released into the blood circulation after plaque rupture. Animal models with reflecting ruptured plaque lesions will be useful to understand efficacy of anticoagulant. In this study, we sought to improve a common arteriovenous shunt model in rabbits, aiming for a model of thrombosis stimulated with tissue factor, and to investigate the anti-thrombotic effect of a direct factor Xa inhibitor TAK-442 in the model.

RESULTS: In the model where thrombus was stimulated with a thrombogenic silk thread soaked with recombinant human tissue factor, thrombus formation was significantly reduced by TAK-442 at more than 37.5 µg/kg, accompanied with prolonged plasma hemostatic parameters. Although efficacious doses of anti-coagulants in ordinary arteriovenous thrombosis models are widely reported to be higher than those in venous thrombosis models, TAK-442 showed its efficacy in the present arteriovenous shunt thrombosis model, with equivalent sensitivity in a previously reported venous model. TAK-442 might be effective under conditions thrombus formed is more influenced by tissue factor pathway.}, } @article {pmid30376833, year = {2018}, author = {Ugelvig, LV and Drijfhout, FP and Kronauer, DJC and Boomsma, JJ and Pedersen, JS and Cremer, S}, title = {Correction to: The introduction history of invasive garden ants in Europe: integrating genetic, chemical and behavioural approaches.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {128}, pmid = {30376833}, issn = {1741-7007}, abstract = {Reinvestigation of the raw data revealed an unfortunate error in Ugelvig et al. 2008 [1].}, } @article {pmid30376820, year = {2018}, author = {Van Zyl, WF and Deane, SM and Dicks, LMT}, title = {In vivo bioluminescence imaging of the spatial and temporal colonization of lactobacillus plantarum 423 and enterococcus mundtii ST4SA in the intestinal tract of mice.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {171}, pmid = {30376820}, issn = {1471-2180}, support = {103843//National Research Foundation of South Africa/ ; }, abstract = {BACKGROUND: Lactic acid bacteria (LAB) are major inhabitants and part of the normal microflora of the gastrointestinal tract (GIT) of humans and animals. Despite substantial evidence supporting the beneficial properties of LAB, only a few studies have addressed the migration and colonization of probiotic bacteria in the GIT. The reason for this is mostly due to the limitations, or lack of, efficient reporter systems. Here we describe the development and application of a non-invasive in vivo bioluminescence reporter system to study, in real-time, the spatial and temporal persistence of Lactobacillus plantarum 423 and Enterococcus mundtii ST4SA in the intestinal tract of mice.

RESULTS: This study reports on the application of the firefly luciferase gene (ffluc) from Photinus pyralis to develop luciferase-expressing L. plantarum 423 and E. mundtii ST4SA, using a Lactococcus lactis NICE system on a high copy number plasmid (pNZ8048) and strong constitutive lactate dehydrogenase gene promoters (Pldh and STldh). The reporter system was used for in vivo and ex vivo monitoring of both probiotic LAB strains in the GIT of mice after single and multiple oral administrations. Enterococcus mundtii ST4SA reached the large intestine 45 min after gavage, while L. plantarum 423 reached the cecum/colon after 90 min. Both strains predominantly colonized the cecum and colon after five consecutive daily administrations. Enterococcus mundtii ST4SA persisted in faeces at higher numbers and for more days compared to L. plantarum 423.

CONCLUSIONS: Our findings demonstrate the efficiency of a high-copy number vector, constitutive promoters and bioluminescence imaging to study the colonization and persistence of L. plantarum 423 and E. mundtii ST4SA in the murine GIT. The system allowed us to differentiate between intestinal transit times of the two strains in the digestive tract. This is the first report of bioluminescence imaging of a luciferase-expressing E. mundtii strain to study colonization dynamics in the murine model. The bioluminescence system developed in this study may be used to study the in vivo colonization dynamics of other probiotic LAB.}, } @article {pmid30376807, year = {2018}, author = {Jing, T and Wang, F and Qi, F and Wang, Z}, title = {Insect anal droplets contain diverse proteins related to gut homeostasis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {784}, pmid = {30376807}, issn = {1471-2164}, support = {31370591//National Natural Science Foundation of China/ ; DL13CA07//Fundamental Research Funds for the Central Universities/ ; LBH-Q14012//Postdoctoral Science Start-up Foundation of the Heilongjiang Province/ ; }, abstract = {BACKGROUND: Insects share similar fundamental molecular principles with mammals in innate immunity. For modulating normal gut microbiota, insects produce phenoloxidase (PO), which is absent in all vertebrates, and reactive nitrogen species (ROS) and antimicrobial proteins (AMPs). However, reports on insect gut phagocytosis are very few. Furthermore, most previous studies measure gene expression at the transcription level. In this study, we provided proteomic evidence on gut modulation of normal microorganisms by investigating the anal droplets from a weevil, Cryptorhynchus lapathi.

RESULTS: The results showed that the anal droplets contained diverse proteins related to physical barriers, epithelium renewal, pattern recognition, phenoloxidase activation, oxidative defense and phagocytosis, but AMPs were not detected. According to annotations, Scarb1, integrin βν, Dscam, spondin or Thbs2s might mediate phagocytosis. As a possible integrin βν pathway, βν activates Rho by an unknown mechanism, and Rho induces accumulation of mDia, which then promotes actin polymerization.

CONCLUSIONS: Our results well demonstrated that insect anal droplets can be used as materials to investigate the defense of a host to gut microorganisms and supported to the hypothesis that gut phagocytosis occurs in insects.}, } @article {pmid30376669, year = {2018}, author = {Höhn, H}, title = {Michael Schmid (1948-2018): A Life Devoted to Science.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000494234}, pmid = {30376669}, issn = {1661-5433}, } @article {pmid30376068, year = {2018}, author = {Reis, M and Vieira, CP and Lata, R and Posnien, N and Vieira, J}, title = {Origin and Consequences of Chromosomal Inversions in the virilis Group of Drosophila.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3152-3166}, pmid = {30376068}, issn = {1759-6653}, abstract = {In Drosophila, large variations in rearrangement rate have been reported among different lineages and among Muller's elements. Nevertheless, the mechanisms that are involved in the generation of inversions, their increase in frequency, as well as their impact on the genome are not completely understood. This is in part due to the lack of comparative studies on species distantly related to Drosophila melanogaster. Therefore, we sequenced and assembled the genomes of two species of the virilis phylad (Drosophila novamexicana [15010-1031.00] and Drosophila americana [SF12]), which are diverging from D. melanogaster for more than 40 Myr. Based on these data, we identified the precise location of six novel inversion breakpoints. A molecular characterization provided clear evidence that DAIBAM (a miniature inverted-repeat transposable element) was involved in the generation of eight out of the nine inversions identified. In contrast to what has been previously reported for D. melanogaster and close relatives, ectopic recombination is thus the prevalent mechanism of generating inversions in species of the virilis phylad. Using pool-sequencing data for three populations of D. americana, we also show that common polymorphic inversions create a high degree of genetic differentiation between populations for chromosomes X, 4, and 5 over large physical distances. We did not find statistically significant differences in expression levels between D. americana (SF12) and D. novamexicana (15010-1031.00) strains for the three genes surveyed (CG9588, Fig 4, and fab1) flanking three inversion breakpoints.}, } @article {pmid30375503, year = {2018}, author = {Nshemereirwe, C}, title = {Tear down visa barriers that block scholarship.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {7}, doi = {10.1038/d41586-018-07179-2}, pmid = {30375503}, issn = {1476-4687}, mesh = {Emigration and Immigration/*legislation & jurisprudence ; Foreign Professional Personnel/*legislation & jurisprudence ; International Cooperation/*legislation & jurisprudence ; Panama ; Research Personnel/*legislation & jurisprudence ; Travel/*legislation & jurisprudence ; Uganda ; }, } @article {pmid30375502, year = {2018}, author = {Perkel, JM}, title = {Why Jupyter is data scientists' computational notebook of choice.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {145-146}, doi = {10.1038/d41586-018-07196-1}, pmid = {30375502}, issn = {1476-4687}, } @article {pmid30375501, year = {2018}, author = {Kaplan, M}, title = {Happy with a 20% chance of sadness.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {20-22}, doi = {10.1038/d41586-018-07181-8}, pmid = {30375501}, issn = {1476-4687}, mesh = {*Affect ; Algorithms ; Cell Phone/statistics & numerical data ; Depression/*diagnosis/psychology ; Female ; Forecasting/*methods ; Galvanic Skin Response ; *Happiness ; Humans ; Male ; *Mobile Applications ; Monitoring, Physiologic/*instrumentation ; Precision Medicine/instrumentation/methods ; Seizures/diagnosis ; *Suicidal Ideation ; Suicide/prevention & control/psychology ; *Wearable Electronic Devices ; }, } @article {pmid30375500, year = {2018}, author = {Kelly, S and Carrington, M}, title = {Chromatin clues to the trypanosome parasite's uniform coat.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {40-42}, doi = {10.1038/d41586-018-07008-6}, pmid = {30375500}, issn = {1476-4687}, mesh = {Animals ; Antigenic Variation ; *Chromatin ; DNA ; *Parasites ; Trypanosoma ; }, } @article {pmid30375499, year = {2018}, author = {Andersen, J and Pașca, SP}, title = {Absent forebrain replaced by embryonic stem cells.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {44-45}, doi = {10.1038/d41586-018-06933-w}, pmid = {30375499}, issn = {1476-4687}, mesh = {Animals ; Blastocyst ; Cell Differentiation ; *Embryonic Stem Cells ; Mice ; Organogenesis ; *Prosencephalon ; }, } @article {pmid30374977, year = {2018}, author = {Eisen, KE}, title = {Digest: Experimental evolution provides a window into the evolution of generalized pollination.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2825-2827}, doi = {10.1111/evo.13638}, pmid = {30374977}, issn = {1558-5646}, abstract = {Do plants with multiple pollinators evolve unique trait combinations or intermediate phenotypes compared to plants with one pollinator? Using experimental evolution, Schiestl et al. (2018) found that plants pollinated by bumblebees and hoverflies evolved trait values not observed in plants pollinated by one taxon, which provides evidence for the existence of a unique generalized pollination phenotype.}, } @article {pmid30374954, year = {2018}, author = {Mikula, P and Petrusková, T and Albrecht, T}, title = {Song complexity-no correlation between standard deviation of frequency and traditionally used song complexity metrics in passerines: A comment on Pearse et al. (2018).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2832-2835}, doi = {10.1111/evo.13634}, pmid = {30374954}, issn = {1558-5646}, support = {14-36098G//Czech Science Foundation/ ; }, abstract = {Recently, Pearse et al. explored the macroecology of passerine song using a large citizen science database of bird songs and machine learning techniques. They used standard deviation of frequency (SDF) as a surrogate for song complexity, finding only weak support for correlation between SDF and life-history traits such as monogamy and sexual dimorphism. Their finding that song complexity increases toward more productive environments and warmer areas seemingly contradicts several previous multitaxonomic studies. By comparing SDF scores with traditionally used song complexity metrics (syllable repertoire size and the number of syllable types per song), we found no evidence of any correlation. This may help to explain the discrepancy between their findings and findings of previous studies. While we agree that simple metrics that can be quantified and compared between multiple, highly variable species are crucial for progress in large-scale analysis of birdsong complexity, the biological relevance of SDF remains unclear and more research is needed to clarify its relevance for further studies of birdsong complexity.}, } @article {pmid30374762, year = {2018}, author = {Ge, J and Liu, C and Tan, J and Bian, L and Chen, S}, title = {Transcriptome analysis of scyphozoan jellyfish Rhopilema esculentum from polyp to medusa identifies potential genes regulating strobilation.}, journal = {Development genes and evolution}, volume = {228}, number = {6}, pages = {243-254}, pmid = {30374762}, issn = {1432-041X}, support = {31702327//national natural science foundation of China/ ; 2017YFE0111100-5//Key Program for International S&T Cooperation Projects of China/ ; }, abstract = {Strobilation is a unique asexual reproduction mode of scyphozoan jellyfish, through which benthic polyp develops into pelagic medusa. It is an orderly metamorphosis process triggered by environmental signals. However, the knowledges of molecular mechanisms under the drastic morphological and physiological changes are still limited. In this study, the transcriptomes from polyps to juvenile medusae at different stages were characterized by RNA-seq in scyphozoan jellyfish Rhopilema esculentum. Among 96,076 de novo assembled unigenes, 7090 differentially expressed genes (DEGs) were identified during the developmental stages. The co-expression pattern analysis of DEGs yielded 15 clusters with different expression patterns. Among them, a cluster with 388 unigenes was related to strobila. In this specific cluster, the GO terms related to "sequence-specific DNA binding transcription factor activity" and "sequence-specific DNA binding" were significantly enriched. Transcription factors, including segmentation protein even-skipped-like, segmentation polarity protein engrailed-like, homeobox proteins Otx-like, Twist-like and Cnox2-Pc-like, as well as genes such as RxR-like and Dmrtf-like, were identified to be potentially involved in strobilation. Their expression patterns and the other 11 TFs/genes involved in strobilation were confirmed with qRT-PCR methods. The present study pointed out the role of transcription factors in strobilation and produced a list of novel candidate genes for further studies. It could provide valuable information for understanding the molecular mechanisms of jellyfish strobilation.}, } @article {pmid30374404, year = {2018}, author = {Varas Enriquez, PJ and McKerracher, LJ and Elliot, MG}, title = {Pre-eclampsia and maternal-fetal conflict.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {217-218}, pmid = {30374404}, issn = {2050-6201}, } @article {pmid30374193, year = {2018}, author = {Romera, M and Talatchian, P and Tsunegi, S and Abreu Araujo, F and Cros, V and Bortolotti, P and Trastoy, J and Yakushiji, K and Fukushima, A and Kubota, H and Yuasa, S and Ernoult, M and Vodenicarevic, D and Hirtzlin, T and Locatelli, N and Querlioz, D and Grollier, J}, title = {Vowel recognition with four coupled spin-torque nano-oscillators.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {230-234}, doi = {10.1038/s41586-018-0632-y}, pmid = {30374193}, issn = {1476-4687}, abstract = {In recent years, artificial neural networks have become the flagship algorithm of artificial intelligence1. In these systems, neuron activation functions are static, and computing is achieved through standard arithmetic operations. By contrast, a prominent branch of neuroinspired computing embraces the dynamical nature of the brain and proposes to endow each component of a neural network with dynamical functionality, such as oscillations, and to rely on emergent physical phenomena, such as synchronization2-6, for solving complex problems with small networks7-11. This approach is especially interesting for hardware implementations, because emerging nanoelectronic devices can provide compact and energy-efficient nonlinear auto-oscillators that mimic the periodic spiking activity of biological neurons12-16. The dynamical couplings between oscillators can then be used to mediate the synaptic communication between the artificial neurons. One challenge for using nanodevices in this way is to achieve learning, which requires fine control and tuning of their coupled oscillations17; the dynamical features of nanodevices can be difficult to control and prone to noise and variability18. Here we show that the outstanding tunability of spintronic nano-oscillators-that is, the possibility of accurately controlling their frequency across a wide range, through electrical current and magnetic field-can be used to address this challenge. We successfully train a hardware network of four spin-torque nano-oscillators to recognize spoken vowels by tuning their frequencies according to an automatic real-time learning rule. We show that the high experimental recognition rates stem from the ability of these oscillators to synchronize. Our results demonstrate that non-trivial pattern classification tasks can be achieved with small hardware neural networks by endowing them with nonlinear dynamical features such as oscillations and synchronization.}, } @article {pmid30374174, year = {2018}, author = {Koerner, SE and Smith, MD and Burkepile, DE and Hanan, NP and Avolio, ML and Collins, SL and Knapp, AK and Lemoine, NP and Forrestel, EJ and Eby, S and Thompson, DI and Aguado-Santacruz, GA and Anderson, JP and Anderson, TM and Angassa, A and Bagchi, S and Bakker, ES and Bastin, G and Baur, LE and Beard, KH and Beever, EA and Bohlen, PJ and Boughton, EH and Canestro, D and Cesa, A and Chaneton, E and Cheng, J and D'Antonio, CM and Deleglise, C and Dembélé, F and Dorrough, J and Eldridge, DJ and Fernandez-Going, B and Fernández-Lugo, S and Fraser, LH and Freedman, B and García-Salgado, G and Goheen, JR and Guo, L and Husheer, S and Karembé, M and Knops, JMH and Kraaij, T and Kulmatiski, A and Kytöviita, MM and Lezama, F and Loucougaray, G and Loydi, A and Milchunas, DG and Milton, SJ and Morgan, JW and Moxham, C and Nehring, KC and Olff, H and Palmer, TM and Rebollo, S and Riginos, C and Risch, AC and Rueda, M and Sankaran, M and Sasaki, T and Schoenecker, KA and Schultz, NL and Schütz, M and Schwabe, A and Siebert, F and Smit, C and Stahlheber, KA and Storm, C and Strong, DJ and Su, J and Tiruvaimozhi, YV and Tyler, C and Val, J and Vandegehuchte, ML and Veblen, KE and Vermeire, LT and Ward, D and Wu, J and Young, TP and Yu, Q and Zelikova, TJ}, title = {Change in dominance determines herbivore effects on plant biodiversity.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1925-1932}, doi = {10.1038/s41559-018-0696-y}, pmid = {30374174}, issn = {2397-334X}, abstract = {Herbivores alter plant biodiversity (species richness) in many of the world's ecosystems, but the magnitude and the direction of herbivore effects on biodiversity vary widely within and among ecosystems. One current theory predicts that herbivores enhance plant biodiversity at high productivity but have the opposite effect at low productivity. Yet, empirical support for the importance of site productivity as a mediator of these herbivore impacts is equivocal. Here, we synthesize data from 252 large-herbivore exclusion studies, spanning a 20-fold range in site productivity, to test an alternative hypothesis-that herbivore-induced changes in the competitive environment determine the response of plant biodiversity to herbivory irrespective of productivity. Under this hypothesis, when herbivores reduce the abundance (biomass, cover) of dominant species (for example, because the dominant plant is palatable), additional resources become available to support new species, thereby increasing biodiversity. By contrast, if herbivores promote high dominance by increasing the abundance of herbivory-resistant, unpalatable species, then resource availability for other species decreases reducing biodiversity. We show that herbivore-induced change in dominance, independent of site productivity or precipitation (a proxy for productivity), is the best predictor of herbivore effects on biodiversity in grassland and savannah sites. Given that most herbaceous ecosystems are dominated by one or a few species, altering the competitive environment via herbivores or by other means may be an effective strategy for conserving biodiversity in grasslands and savannahs globally.}, } @article {pmid30374173, year = {2018}, author = {Denk, T and Zohner, CM and Grimm, GW and Renner, SS}, title = {Plant fossils reveal major biomes occupied by the late Miocene Old-World Pikermian fauna.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1864-1870}, doi = {10.1038/s41559-018-0695-z}, pmid = {30374173}, issn = {2397-334X}, abstract = {Reconstruction of palaeobiomes, ancient communities that exhibit a physiognomic and functional structure controlled by their environment, depends on proxies from different disciplines. Based on terrestrial mammal fossils, the late Miocene vegetation from China to the eastern Mediterranean and East Africa has been reconstructed as a single cohesive biome with increasingly arid conditions, with modern African savannahs the surviving remnant. Here, we test this reconstruction using plant fossils spanning 14-4 million years ago from sites in Greece, Bulgaria, Turkey, the Tian Shan Mountains and Baode County in China, and East Africa. The western Eurasian sites had a continuous forest cover of deciduous or evergreen angiosperms and gymnosperms, with 15% of 1,602 fossil occurrences representing conifers, which were present at all but one of the sites. Raup-Crick analyses reveal high floristic similarity between coeval eastern Mediterranean and Chinese sites, and low similarity between Eurasian and African sites. The disagreement between plant-based reconstructions, which imply that late Miocene western Eurasia was covered by evergreen needleleaf forests and mixed forests, and mammal-based reconstructions, which imply a savannah biome, throws into doubt the approach of inferring Miocene precipitation and open savannah habitats solely from mammalian dental traits. Organismal communities are constantly changing in their species composition, and neither animal nor plant traits by themselves are sufficient to infer entire ancient biomes. The plant fossil record, however, unambiguously rejects the existence of a cohesive savannah biome from eastern Asia to northeast Africa.}, } @article {pmid30374172, year = {2018}, author = {Zarrillo, S and Gaikwad, N and Lanaud, C and Powis, T and Viot, C and Lesur, I and Fouet, O and Argout, X and Guichoux, E and Salin, F and Solorzano, RL and Bouchez, O and Vignes, H and Severts, P and Hurtado, J and Yepez, A and Grivetti, L and Blake, M and Valdez, F}, title = {The use and domestication of Theobroma cacao during the mid-Holocene in the upper Amazon.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1879-1888}, doi = {10.1038/s41559-018-0697-x}, pmid = {30374172}, issn = {2397-334X}, abstract = {Cacao (Theobroma cacao L.) is an important economic crop, yet studies of its domestication history and early uses are limited. Traditionally, cacao is thought to have been first domesticated in Mesoamerica. However, genomic research shows that T. cacao's greatest diversity is in the upper Amazon region of northwest South America, pointing to this region as its centre of origin. Here, we report cacao use identified by three independent lines of archaeological evidence-cacao starch grains, absorbed theobromine residues and ancient DNA-dating from approximately 5,300 years ago recovered from the Santa Ana-La Florida (SALF) site in southeast Ecuador. To our knowledge, these findings constitute the earliest evidence of T. cacao use in the Americas and the first unequivocal archaeological example of its pre-Columbian use in South America. They also reveal the upper Amazon region as the oldest centre of cacao domestication yet identified.}, } @article {pmid30374171, year = {2018}, author = {Roberts, P and Stewart, M and Alagaili, AN and Breeze, P and Candy, I and Drake, N and Groucutt, HS and Scerri, EML and Lee-Thorp, J and Louys, J and Zalmout, IS and Al-Mufarreh, YSA and Zech, J and Alsharekh, AM and Al Omari, A and Boivin, N and Petraglia, M}, title = {Fossil herbivore stable isotopes reveal middle Pleistocene hominin palaeoenvironment in 'Green Arabia'.}, journal = {Nature ecology & evolution}, volume = {2}, number = {12}, pages = {1871-1878}, doi = {10.1038/s41559-018-0698-9}, pmid = {30374171}, issn = {2397-334X}, abstract = {Despite its largely hyper-arid and inhospitable climate today, the Arabian Peninsula is emerging as an important area for investigating Pleistocene hominin dispersals. Recently, a member of our own species was found in northern Arabia dating to ca. 90 ka, while stone tools and fossil finds have hinted at an earlier, middle Pleistocene, hominin presence. However, there remain few direct insights into Pleistocene environments, and associated hominin adaptations, that accompanied the movement of populations into this region. Here, we apply stable carbon and oxygen isotope analysis to fossil mammal tooth enamel (n = 21) from the middle Pleistocene locality of Ti's al Ghadah in Saudi Arabia associated with newly discovered stone tools and probable cutmarks. The results demonstrate productive grasslands in the interior of the Arabian Peninsula ca. 300-500 ka, as well as aridity levels similar to those found in open savannah settings in eastern Africa today. The association between this palaeoenvironmental information and the earliest traces for hominin activity in this part of the world lead us to argue that middle Pleistocene hominin dispersals into the interior of the Arabian Peninsula required no major novel adaptation.}, } @article {pmid30374170, year = {2018}, author = {Mondotte, JA and Gausson, V and Frangeul, L and Blanc, H and Lambrechts, L and Saleh, MC}, title = {Immune priming and clearance of orally acquired RNA viruses in Drosophila.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1394-1403}, doi = {10.1038/s41564-018-0265-9}, pmid = {30374170}, issn = {2058-5276}, abstract = {Immune responses in insects are differentially triggered depending on the infection route used by the pathogen. In most studies involving Drosophila melanogaster and viruses, infection is done by injection, while oral infection, which is probably the most common route of viral entry in nature, remains unexplored. Here, we orally infected adults and larvae from wild-type and RNA interference (RNAi) mutant flies with different RNA viruses. We found that, in contrast with what is observed following virus injection, oral infections initiated at larval or adult stages are cleared in adult flies. Virus elimination occurred despite a larger infectious dose than for injected flies and evidence of viral replication. RNAi mutant flies suffered greater mortality relative to wild-type flies following oral infection, but they also eliminated the virus, implying that RNAi is not essential for viral clearance and that other immune mechanisms act during oral infections. We further showed that information of infection by RNA viruses acquired orally leaves a trace under a DNA form, which confers protection against future reinfection by the same virus. Together, this work presents evidence of clearance and immune priming for RNA viruses in insects and challenges the current view of antiviral immunity in insects.}, } @article {pmid30374169, year = {2018}, author = {Olmo, RP and Ferreira, AGA and Izidoro-Toledo, TC and Aguiar, ERGR and de Faria, IJS and de Souza, KPR and Osório, KP and Kuhn, L and Hammann, P and de Andrade, EG and Todjro, YM and Rocha, MN and Leite, THJF and Amadou, SCG and Armache, JN and Paro, S and de Oliveira, CD and Carvalho, FD and Moreira, LA and Marois, E and Imler, JL and Marques, JT}, title = {Control of dengue virus in the midgut of Aedes aegypti by ectopic expression of the dsRNA-binding protein Loqs2.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1385-1393}, doi = {10.1038/s41564-018-0268-6}, pmid = {30374169}, issn = {2058-5276}, abstract = {Dengue virus (DENV) is an arbovirus transmitted to humans by Aedes mosquitoes1. In the insect vector, the small interfering RNA (siRNA) pathway is an important antiviral mechanism against DENV2-5. However, it remains unclear when and where the siRNA pathway acts during the virus cycle. Here, we show that the siRNA pathway fails to efficiently silence DENV in the midgut of Aedes aegypti although it is essential to restrict systemic replication. Accumulation of DENV-derived siRNAs in the midgut reveals that impaired silencing results from a defect downstream of small RNA biogenesis. Notably, silencing triggered by endogenous and exogenous dsRNAs remained effective in the midgut where known components of the siRNA pathway, including the double-stranded RNA (dsRNA)-binding proteins Loquacious and r2d2, had normal expression levels. We identified an Aedes-specific paralogue of loquacious and r2d2, hereafter named loqs2, which is not expressed in the midgut. Loqs2 interacts with Loquacious and r2d2 and is required to control systemic replication of DENV and also Zika virus. Furthermore, ectopic expression of Loqs2 in the midgut of transgenic mosquitoes is sufficient to restrict DENV replication and dissemination. Together, our data reveal a mechanism of tissue-specific regulation of the mosquito siRNA pathway controlled by Loqs2.}, } @article {pmid30374168, year = {2018}, author = {Reese, AT and Pereira, FC and Schintlmeister, A and Berry, D and Wagner, M and Hale, LP and Wu, A and Jiang, S and Durand, HK and Zhou, X and Premont, RT and Diehl, AM and O'Connell, TM and Alberts, SC and Kartzinel, TR and Pringle, RM and Dunn, RR and Wright, JP and David, LA}, title = {Microbial nitrogen limitation in the mammalian large intestine.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1441-1450}, pmid = {30374168}, issn = {2058-5276}, abstract = {Resource limitation is a fundamental factor governing the composition and function of ecological communities. However, the role of resource supply in structuring the intestinal microbiome has not been established and represents a challenge for mammals that rely on microbial symbionts for digestion: too little supply might starve the microbiome while too much might starve the host. We present evidence that microbiota occupy a habitat that is limited in total nitrogen supply within the large intestines of 30 mammal species. Lowering dietary protein levels in mice reduced their faecal concentrations of bacteria. A gradient of stoichiometry along the length of the gut was consistent with the hypothesis that intestinal nitrogen limitation results from host absorption of dietary nutrients. Nitrogen availability is also likely to be shaped by host-microbe interactions: levels of host-secreted nitrogen were altered in germ-free mice and when bacterial loads were reduced via experimental antibiotic treatment. Single-cell spectrometry revealed that members of the phylum Bacteroidetes consumed nitrogen in the large intestine more readily than other commensal taxa did. Our findings support a model where nitrogen limitation arises from preferential host use of dietary nutrients. We speculate that this resource limitation could enable hosts to regulate microbial communities in the large intestine. Commensal microbiota may have adapted to nitrogen-limited settings, suggesting one reason why excess dietary protein has been associated with degraded gut-microbial ecosystems.}, } @article {pmid30374149, year = {2018}, author = {Hofer, U}, title = {EV-D68 steps up its neurotropism.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {718-719}, doi = {10.1038/s41579-018-0114-0}, pmid = {30374149}, issn = {1740-1534}, } @article {pmid30374148, year = {2018}, author = {Du Toit, A}, title = {Sharing with your community.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {718-719}, doi = {10.1038/s41579-018-0113-1}, pmid = {30374148}, issn = {1740-1534}, } @article {pmid30374080, year = {2018}, author = {Rivest, S}, title = {A 'don't eat me' immune signal protects neuronal connections.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {42-43}, doi = {10.1038/d41586-018-07165-8}, pmid = {30374080}, issn = {1476-4687}, } @article {pmid30374075, year = {2018}, author = {Tarabichi, M and Martincorena, I and Gerstung, M and Leroi, AM and Markowetz, F and , and Spellman, PT and Morris, QD and Lingjærde, OC and Wedge, DC and Van Loo, P}, title = {Neutral tumor evolution?.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1630-1633}, doi = {10.1038/s41588-018-0258-x}, pmid = {30374075}, issn = {1546-1718}, } @article {pmid30374074, year = {2018}, author = {O'Connor, LJ and Price, AL}, title = {Distinguishing genetic correlation from causation across 52 diseases and complex traits.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1728-1734}, doi = {10.1038/s41588-018-0255-0}, pmid = {30374074}, issn = {1546-1718}, abstract = {Mendelian randomization, a method to infer causal relationships, is confounded by genetic correlations reflecting shared etiology. We developed a model in which a latent causal variable mediates the genetic correlation; trait 1 is partially genetically causal for trait 2 if it is strongly genetically correlated with the latent causal variable, quantified using the genetic causality proportion. We fit this model using mixed fourth moments [Formula: see text] and [Formula: see text] of marginal effect sizes for each trait; if trait 1 is causal for trait 2, then SNPs affecting trait 1 (large [Formula: see text]) will have correlated effects on trait 2 (large α1α2), but not vice versa. In simulations, our method avoided false positives due to genetic correlations, unlike Mendelian randomization. Across 52 traits (average n = 331,000), we identified 30 causal relationships with high genetic causality proportion estimates. Novel findings included a causal effect of low-density lipoprotein on bone mineral density, consistent with clinical trials of statins in osteoporosis.}, } @article {pmid30374073, year = {2018}, author = {Heide, T and Zapata, L and Williams, MJ and Werner, B and Caravagna, G and Barnes, CP and Graham, TA and Sottoriva, A}, title = {Reply to 'Neutral tumor evolution?'.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1633-1637}, doi = {10.1038/s41588-018-0256-z}, pmid = {30374073}, issn = {1546-1718}, support = {097319//Wellcome Trust/United Kingdom ; }, } @article {pmid30374071, year = {2018}, author = {Wallace, DC}, title = {Mitochondrial genetic medicine.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1642-1649}, doi = {10.1038/s41588-018-0264-z}, pmid = {30374071}, issn = {1546-1718}, abstract = {Inherited mitochondrial DNA (mtDNA) diseases were discovered 30 years ago, and their characterization has provided a new perspective on the etiology of the common metabolic and degenerative diseases, cancer, and aging. The maternally inherited mtDNA contains 37 critical bioenergetic genes that are present in hundreds of copies per cell, but the 'mitochondrial genome' encompasses an additional 1,000-2,000 nuclear DNA (nDNA) mitochondrial genes. The interaction between these two mitochondrial genetic systems provides explanations for phenomena such as the non-Mendelian transmission of the common 'complex' diseases, age-related disease risk and progression, variable penetrance and expressivity, and gene-environment interactions. Thus, mtDNA genetics contributes to the quantitative and environmental components of human genetics that cannot be explained by Mendelian genetics. Because mtDNA is maternally inherited and cytoplasmic, it has fostered the first germline gene therapy, nuclear transplantation. However, effective interventions are still lacking for existing patients with mitochondrial dysfunction.}, } @article {pmid30374070, year = {2018}, author = {Werner, B and Williams, MJ and Barnes, CP and Graham, TA and Sottoriva, A}, title = {Reply to 'Currently available bulk sequencing data do not necessarily support a model of neutral tumor evolution'.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1624-1626}, doi = {10.1038/s41588-018-0235-4}, pmid = {30374070}, issn = {1546-1718}, support = {097319//Wellcome Trust/United Kingdom ; }, } @article {pmid30374069, year = {2018}, author = {Styrkarsdottir, U and Lund, SH and Thorleifsson, G and Zink, F and Stefansson, OA and Sigurdsson, JK and Juliusson, K and Bjarnadottir, K and Sigurbjornsdottir, S and Jonsson, S and Norland, K and Stefansdottir, L and Sigurdsson, A and Sveinbjornsson, G and Oddsson, A and Bjornsdottir, G and Gudmundsson, RL and Halldorsson, GH and Rafnar, T and Jonsdottir, I and Steingrimsson, E and Norddahl, GL and Masson, G and Sulem, P and Jonsson, H and Ingvarsson, T and Gudbjartsson, DF and Thorsteinsdottir, U and Stefansson, K}, title = {Meta-analysis of Icelandic and UK data sets identifies missense variants in SMO, IL11, COL11A1 and 13 more new loci associated with osteoarthritis.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1681-1687}, doi = {10.1038/s41588-018-0247-0}, pmid = {30374069}, issn = {1546-1718}, abstract = {Osteoarthritis has a highly negative impact on quality of life because of the associated pain and loss of joint function. Here we describe the largest meta-analysis so far of osteoarthritis of the hip and the knee in samples from Iceland and the UK Biobank (including 17,151 hip osteoarthritis patients, 23,877 knee osteoarthritis patients, and more than 562,000 controls). We found 23 independent associations at 22 loci in the additive meta-analyses, of which 16 of the loci were novel: 12 for hip and 4 for knee osteoarthritis. Two associations are between rare or low-frequency missense variants and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds ratio (OR) = 2.8, P = 7.9 × 10-12, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%, OR = 1.30, P = 2.1 × 10-11, p.Arg112His). A common missense variant in the COL11A1 gene also associates with hip osteoarthritis (rs3753841, frequency 61%, P = 5.2 × 10-10, OR = 1.08, p.Pro1284Leu). In addition, using a recessive model, we confirm an association between hip osteoarthritis and a variant of CHADL1 (rs117018441, P = 1.8 × 10-25, OR = 5.9). Furthermore, we observe a complex relationship between height and risk of osteoarthritis.}, } @article {pmid30374068, year = {2018}, author = {Oudelaar, AM and Davies, JOJ and Hanssen, LLP and Telenius, JM and Schwessinger, R and Liu, Y and Brown, JM and Downes, DJ and Chiariello, AM and Bianco, S and Nicodemi, M and Buckle, VJ and Dekker, J and Higgs, DR and Hughes, JR}, title = {Single-allele chromatin interactions identify regulatory hubs in dynamic compartmentalized domains.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1744-1751}, pmid = {30374068}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; R01 HG003143/HG/NHGRI NIH HHS/United States ; }, abstract = {The promoters of mammalian genes are commonly regulated by multiple distal enhancers, which physically interact within discrete chromatin domains. How such domains form and how the regulatory elements within them interact in single cells is not understood. To address this we developed Tri-C, a new chromosome conformation capture (3C) approach, to characterize concurrent chromatin interactions at individual alleles. Analysis by Tri-C identifies heterogeneous patterns of single-allele interactions between CTCF boundary elements, indicating that the formation of chromatin domains likely results from a dynamic process. Within these domains, we observe specific higher-order structures that involve simultaneous interactions between multiple enhancers and promoters. Such regulatory hubs provide a structural basis for understanding how multiple cis-regulatory elements act together to establish robust regulation of gene expression.}, } @article {pmid30374067, year = {2018}, author = {McDonald, TO and Chakrabarti, S and Michor, F}, title = {Currently available bulk sequencing data do not necessarily support a model of neutral tumor evolution.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1620-1623}, doi = {10.1038/s41588-018-0217-6}, pmid = {30374067}, issn = {1546-1718}, } @article {pmid30374066, year = {2018}, author = {Gayden, T and Sepulveda, FE and Khuong-Quang, DA and Pratt, J and Valera, ET and Garrigue, A and Kelso, S and Sicheri, F and Mikael, LG and Hamel, N and Bajic, A and Dali, R and Deshmukh, S and Dervovic, D and Schramek, D and Guerin, F and Taipale, M and Nikbakht, H and Majewski, J and Moshous, D and Charlebois, J and Abish, S and Bole-Feysot, C and Nitschke, P and Bader-Meunier, B and Mitchell, D and Thieblemont, C and Battistella, M and Gravel, S and Nguyen, VH and Conyers, R and Diana, JS and McCormack, C and Prince, HM and Besnard, M and Blanche, S and Ekert, PG and Fraitag, S and Foulkes, WD and Fischer, A and Neven, B and Michonneau, D and de Saint Basile, G and Jabado, N}, title = {Germline HAVCR2 mutations altering TIM-3 characterize subcutaneous panniculitis-like T cell lymphomas with hemophagocytic lymphohistiocytic syndrome.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1650-1657}, doi = {10.1038/s41588-018-0251-4}, pmid = {30374066}, issn = {1546-1718}, abstract = {Subcutaneous panniculitis-like T cell lymphoma (SPTCL), a non-Hodgkin lymphoma, can be associated with hemophagocytic lymphohistiocytosis (HLH), a life-threatening immune activation that adversely affects survival1,2. T cell immunoglobulin mucin 3 (TIM-3) is a modulator of immune responses expressed on subgroups of T and innate immune cells. We identify in ~60% of SPTCL cases germline, loss-of-function, missense variants altering highly conserved residues of TIM-3, c.245A>G (p.Tyr82Cys) and c.291A>G (p.Ile97Met), each with specific geographic distribution. The variant encoding p.Tyr82Cys TIM-3 occurs on a potential founder chromosome in patients with East Asian and Polynesian ancestry, while p.Ile97Met TIM-3 occurs in patients with European ancestry. Both variants induce protein misfolding and abrogate TIM-3's plasma membrane expression, leading to persistent immune activation and increased production of inflammatory cytokines, including tumor necrosis factor-α and interleukin-1β, promoting HLH and SPTCL. Our findings highlight HLH-SPTCL as a new genetic entity and identify mutations causing TIM-3 alterations as a causative genetic defect in SPTCL. While HLH-SPTCL patients with mutant TIM-3 benefit from immunomodulation, therapeutic repression of the TIM-3 checkpoint may have adverse consequences.}, } @article {pmid30373845, year = {2018}, author = {Schally, AV and Wang, H and He, J and Cai, R and Sha, W and Popovics, P and Perez, R and Vidaurre, I and Zhang, X}, title = {Agonists of growth hormone-releasing hormone (GHRH) inhibit human experimental cancers in vivo by down-regulating receptors for GHRH.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12028-12033}, pmid = {30373845}, issn = {1091-6490}, mesh = {Alternative Splicing/drug effects ; Animals ; Apoptosis/drug effects ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cell Line, Tumor/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Down-Regulation/drug effects ; Female ; Growth Hormone-Releasing Hormone/agonists/pharmacology ; Humans ; Mice ; Mice, Nude ; RNA Splicing/drug effects ; Receptors, Neuropeptide/*drug effects ; Receptors, Pituitary Hormone-Regulating Hormone/*drug effects ; Sermorelin/*analogs & derivatives/metabolism/pharmacology ; Small Cell Lung Carcinoma/metabolism ; Xenograft Model Antitumor Assays/methods ; }, abstract = {The effects of the growth hormone-releasing hormone (GHRH) agonist MR409 on various human cancer cells were investigated. In H446 small cell lung cancer (SCLC) and HCC827 and H460 (non-SCLC) cells, MR409 promoted cell viability, reduced cell apoptosis, and induced the production of cellular cAMP in vitro. Western blot analyses showed that treatment of cancer cells with MR409 up-regulated the expression of cyclins D1 and D2 and cyclin-dependent kinases 4 and 6, down-regulated p27kip1, and significantly increased the expression of the pituitary-type GHRH receptor (pGHRH-R) and its splice-variant (SV1). Hence, in vitro MR409 exerts agonistic action on lung cancer cells in contrast to GHRH antagonists. However, in vivo, MR409 inhibited growth of lung cancers xenografted into nude mice. MR409 given s.c. at 5 μg/day for 4 to 8 weeks significantly suppressed growth of HCC827, H460, and H446 tumors by 48.2%, 48.7%, and 65.6%, respectively. This inhibition of tumor growth by MR409 was accompanied by the down-regulation of the expression of pGHRH-R and SV1 in the pituitary gland and tumors. Tumor inhibitory effects of MR409 in vivo were also observed in other human cancers, including gastric, pancreatic, urothelial, prostatic, mammary, and colorectal. This inhibition of tumor growth parallel to the down-regulation of GHRH-Rs is similar and comparable to the suppression of sex hormone-dependent cancers after the down-regulation of receptors for luteinizing hormone-releasing hormone (LHRH) by LHRH agonists. Further oncological investigations with GHRH agonists are needed to elucidate the underlying mechanisms.}, } @article {pmid30373844, year = {2018}, author = {Scheffer, M and Bolhuis, JE and Borsboom, D and Buchman, TG and Gijzel, SMW and Goulson, D and Kammenga, JE and Kemp, B and van de Leemput, IA and Levin, S and Martin, CM and Melis, RJF and van Nes, EH and Romero, LM and Olde Rikkert, MGM}, title = {Quantifying resilience of humans and other animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11883-11890}, pmid = {30373844}, issn = {1091-6490}, mesh = {Adaptation, Physiological/*physiology ; Animals ; Conservation of Natural Resources/methods ; Health/*classification ; Holistic Health ; Humans ; Resilience, Psychological/*classification ; }, abstract = {All life requires the capacity to recover from challenges that are as inevitable as they are unpredictable. Understanding this resilience is essential for managing the health of humans and their livestock. It has long been difficult to quantify resilience directly, forcing practitioners to rely on indirect static indicators of health. However, measurements from wearable electronics and other sources now allow us to analyze the dynamics of physiology and behavior with unsurpassed resolution. The resulting flood of data coincides with the emergence of novel analytical tools for estimating resilience from the pattern of microrecoveries observed in natural time series. Such dynamic indicators of resilience may be used to monitor the risk of systemic failure across systems ranging from organs to entire organisms. These tools invite a fundamental rethinking of our approach to the adaptive management of health and resilience.}, } @article {pmid30373843, year = {2018}, author = {Swift-Gallant, A and Jordan, CL and Breedlove, SM}, title = {Consequences of cesarean delivery for neural development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11664-11666}, pmid = {30373843}, issn = {1091-6490}, mesh = {Animals ; Brain ; Cell Death ; *Cesarean Section ; Female ; Mice ; Neurogenesis ; *Parturition ; Pregnancy ; }, } @article {pmid30373842, year = {2018}, author = {Qi, T and Seong, K and Thomazella, DPT and Kim, JR and Pham, J and Seo, E and Cho, MJ and Schultink, A and Staskawicz, BJ}, title = {NRG1 functions downstream of EDS1 to regulate TIR-NLR-mediated plant immunity in Nicotiana benthamiana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10979-E10987}, pmid = {30373842}, issn = {1091-6490}, mesh = {B-Lymphocyte Subsets/metabolism ; DNA-Binding Proteins ; NLR Proteins/metabolism ; Neuregulin-1/genetics/physiology ; Plant Diseases ; Plant Immunity ; Plant Proteins/genetics ; Protein Domains ; Proteins/genetics ; Pseudomonas ; Signal Transduction ; Tobacco/*genetics/*metabolism ; Transcriptome ; Xanthomonas ; }, abstract = {Effector-triggered immunity (ETI) in plants involves a large family of nucleotide-binding leucine-rich repeat (NLR) immune receptors, including Toll/IL-1 receptor-NLRs (TNLs) and coiled-coil NLRs (CNLs). Although various NLR immune receptors are known, a mechanistic understanding of NLR function in ETI remains unclear. The TNL Recognition of XopQ 1 (Roq1) recognizes the effectors XopQ and HopQ1 from Xanthomonas and Pseudomonas, respectively, which activates resistance to Xanthomonas euvesicatoria and Xanthomonas gardneri in an Enhanced Disease Susceptibility 1 (EDS1)-dependent way in Nicotiana benthamiana In this study, we found that the N. benthamiana N requirement gene 1 (NRG1), a CNL protein required for the tobacco TNL protein N-mediated resistance to tobacco mosaic virus, is also essential for immune signaling [including hypersensitive response (HR)] triggered by the TNLs Roq1 and Recognition of Peronospora parasitica 1 (RPP1), but not by the CNLs Bs2 and Rps2, suggesting that NRG1 may be a conserved key component in TNL signaling pathways. Besides EDS1, Roq1 and NRG1 are necessary for resistance to Xanthomonas and Pseudomonas in N. benthamiana NRG1 functions downstream of Roq1 and EDS1 and physically associates with EDS1 in mediating XopQ-Roq1-triggered immunity. Moreover, RNA sequencing analysis showed that XopQ-triggered gene-expression profile changes in N. benthamiana were almost entirely mediated by Roq1 and EDS1 and were largely regulated by NRG1. Overall, our study demonstrates that NRG1 is a key component that acts downstream of EDS1 to mediate various TNL signaling pathways, including Roq1 and RPP1-mediated HR, resistance to Xanthomonas and Pseudomonas, and XopQ-regulated transcriptional changes in N. benthamiana.}, } @article {pmid30373841, year = {2018}, author = {}, title = {Correction for Bang et al., Biophysical and functional characterization of Norrin signaling through Frizzled4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10807}, doi = {10.1073/pnas.1817333115}, pmid = {30373841}, issn = {1091-6490}, } @article {pmid30373840, year = {2018}, author = {Spanò, G and Gómez, RL and Demara, BI and Alt, M and Cowen, SL and Edgin, JO}, title = {REM sleep in naps differentially relates to memory consolidation in typical preschoolers and children with Down syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11844-11849}, pmid = {30373840}, issn = {1091-6490}, mesh = {Attention ; Child ; Child, Preschool ; Down Syndrome/physiopathology ; Female ; Humans ; Learning/physiology ; Male ; Memory Consolidation/*physiology ; Sleep/*physiology ; Sleep, REM/*physiology ; Verbal Learning/physiology ; Wakefulness/physiology ; }, abstract = {Sleep is recognized as a physiological state associated with learning, with studies showing that knowledge acquisition improves with naps. Little work has examined sleep-dependent learning in people with developmental disorders, for whom sleep quality is often impaired. We examined the effect of natural, in-home naps on word learning in typical young children and children with Down syndrome (DS). Despite similar immediate memory retention, naps benefitted memory performance in typical children but hindered performance in children with DS, who retained less when tested after a nap, but were more accurate after a wake interval. These effects of napping persisted 24 h later in both groups, even after an intervening overnight period of sleep. During naps in typical children, memory retention for object-label associations correlated positively with percent of time in rapid eye movement (REM) sleep. However, in children with DS, a population with reduced REM, learning was impaired, but only after the nap. This finding shows that a nap can increase memory loss in a subpopulation, highlighting that naps are not universally beneficial. Further, in healthy preschooler's naps, processes in REM sleep may benefit learning.}, } @article {pmid30373839, year = {2018}, author = {Mehta, AP and Supekova, L and Chen, JH and Pestonjamasp, K and Webster, P and Ko, Y and Henderson, SC and McDermott, G and Supek, F and Schultz, PG}, title = {Engineering yeast endosymbionts as a step toward the evolution of mitochondria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11796-11801}, pmid = {30373839}, issn = {1091-6490}, support = {P41 GM103445/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/metabolism ; Amino Acid Sequence ; Bioengineering/*methods ; Biological Evolution ; Escherichia coli/genetics/metabolism ; Mitochondria/*genetics/metabolism ; Models, Biological ; Saccharomyces cerevisiae/genetics/metabolism ; Symbiosis/*genetics ; Thiamine/metabolism ; }, abstract = {It has been hypothesized that mitochondria evolved from a bacterial ancestor that initially became established in an archaeal host cell as an endosymbiont. Here we model this first stage of mitochondrial evolution by engineering endosymbiosis between Escherichia coli and Saccharomyces cerevisiae An ADP/ATP translocase-expressing E. coli provided ATP to a respiration-deficient cox2 yeast mutant and enabled growth of a yeast-E. coli chimera on a nonfermentable carbon source. In a reciprocal fashion, yeast provided thiamin to an endosymbiotic E. coli thiamin auxotroph. Expression of several SNARE-like proteins in E. coli was also required, likely to block lysosomal degradation of intracellular bacteria. This chimeric system was stable for more than 40 doublings, and GFP-expressing E. coli endosymbionts could be observed in the yeast by fluorescence microscopy and X-ray tomography. This readily manipulated system should allow experimental delineation of host-endosymbiont adaptations that occurred during evolution of the current, highly reduced mitochondrial genome.}, } @article {pmid30373838, year = {2018}, author = {Vaughn, TL and Bell, CS and Pickering, CK and Schwietzke, S and Heath, GA and Pétron, G and Zimmerle, DJ and Schnell, RC and Nummedal, D}, title = {Temporal variability largely explains top-down/bottom-up difference in methane emission estimates from a natural gas production region.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11712-11717}, pmid = {30373838}, issn = {1091-6490}, abstract = {This study spatially and temporally aligns top-down and bottom-up methane emission estimates for a natural gas production basin, using multiscale emission measurements and detailed activity data reporting. We show that episodic venting from manual liquid unloadings, which occur at a small fraction of natural gas well pads, drives a factor-of-two temporal variation in the basin-scale emission rate of a US dry shale gas play. The midafternoon peak emission rate aligns with the sampling time of all regional aircraft emission studies, which target well-mixed boundary layer conditions present in the afternoon. A mechanistic understanding of emission estimates derived from various methods is critical for unbiased emission verification and effective greenhouse gas emission mitigation. Our results demonstrate that direct comparison of emission estimates from methods covering widely different timescales can be misleading.}, } @article {pmid30373837, year = {2018}, author = {Sulpis, O and Boudreau, BP and Mucci, A and Jenkins, C and Trossman, DS and Arbic, BK and Key, RM}, title = {Current CaCO3 dissolution at the seafloor caused by anthropogenic CO2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11700-11705}, pmid = {30373837}, issn = {1091-6490}, mesh = {Calcium Carbonate/analysis/*chemistry ; Carbon Dioxide/*adverse effects/analysis ; Ecosystem ; Human Activities ; Hydrogen-Ion Concentration ; Oceans and Seas ; Pacific Ocean ; Seawater/analysis/*chemistry ; Solubility ; Water ; }, abstract = {Oceanic uptake of anthropogenic CO2 leads to decreased pH, carbonate ion concentration, and saturation state with respect to CaCO3 minerals, causing increased dissolution of these minerals at the deep seafloor. This additional dissolution will figure prominently in the neutralization of man-made CO2 However, there has been no concerted assessment of the current extent of anthropogenic CaCO3 dissolution at the deep seafloor. Here, recent databases of bottom-water chemistry, benthic currents, and CaCO3 content of deep-sea sediments are combined with a rate model to derive the global distribution of benthic calcite dissolution rates and obtain primary confirmation of an anthropogenic component. By comparing preindustrial with present-day rates, we determine that significant anthropogenic dissolution now occurs in the western North Atlantic, amounting to 40-100% of the total seafloor dissolution at its most intense locations. At these locations, the calcite compensation depth has risen ∼300 m. Increased benthic dissolution was also revealed at various hot spots in the southern extent of the Atlantic, Indian, and Pacific Oceans. Our findings place constraints on future predictions of ocean acidification, are consequential to the fate of benthic calcifiers, and indicate that a by-product of human activities is currently altering the geological record of the deep sea.}, } @article {pmid30373836, year = {2018}, author = {Tushingham, S and Snyder, CM and Brownstein, KJ and Damitio, WJ and Gang, DR}, title = {Biomolecular archaeology reveals ancient origins of indigenous tobacco smoking in North American Plateau.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11742-11747}, pmid = {30373836}, issn = {1091-6490}, mesh = {American Native Continental Ancestry Group/genetics ; Archaeology/*methods ; Gas Chromatography-Mass Spectrometry/methods ; History, Ancient ; Humans ; Indians, North American/history ; Nicotine/analysis ; North America ; Tobacco/genetics/metabolism ; Tobacco Smoking/*history ; United States ; }, abstract = {Chemical analysis of residues contained in the matrix of stone smoking pipes reveal a substantial direct biomolecular record of ancient tobacco (Nicotiana) smoking practices in the North American interior northwest (Plateau), in an area where tobacco was often portrayed as a Euro-American-introduced postcontact trade commodity. Nicotine, a stimulant alkaloid and biomarker for tobacco, was identified via ultra-performance liquid chromatography-mass spectrometry in 8 of 12 analyzed pipes and pipe fragments from five sites in the Columbia River Basin, southeastern Washington State. The specimens date from 1200 cal BP to historic times, confirming the deep time continuity of intoxicant use and indigenous smoking practices in northwestern North America. The results indicate that hunting and gathering communities in the region, including ancestral Nez Perce peoples, established a tobacco smoking complex of wild (indigenous) tobacco well before the main domesticated tobacco (Nicotiana tabacum) was introduced by contact-era fur traders and settlers after the 1790s. This is the longest continuous biomolecular record of ancient tobacco smoking from a single region anywhere in the world-initially during an era of pithouse development, through the late precontact equestrian era, and into the historic period. This contradicts some ethnohistorical data indicating that kinnikinnick, or bearberry (Arctostaphylos uva-ursi) was the primary precontact smoke plant in the study area. Early use likely involved the management and cultivation of indigenous tobaccos (Nicotiana quadrivalvis or Nicotiana attenuata), species that are today exceedingly rare in the region and seem to have been abandoned as smoke plants after the entry of trade tobacco.}, } @article {pmid30373835, year = {2018}, author = {Pearson, AR and Schuldt, JP and Romero-Canyas, R and Ballew, MT and Larson-Konar, D}, title = {Diverse segments of the US public underestimate the environmental concerns of minority and low-income Americans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12429-12434}, doi = {10.1073/pnas.1804698115}, pmid = {30373835}, issn = {1091-6490}, abstract = {In a nationally representative survey experiment, diverse segments of the US public underestimated the environmental concerns of nonwhite and low-income Americans and misperceived them as lower than those of white and more affluent Americans. Moreover, both whites and nonwhites and higher- and lower-income respondents associated the term "environmentalist" with whites and the well-educated, suggesting that shared cultural stereotypes may drive these misperceptions. This environmental belief paradox-a tendency to misperceive groups that are among the most environmentally concerned and most vulnerable to a wide range of environmental impacts as least concerned about the environment-was largely invariant across demographic groups and also extended to the specific issue of climate change. Suggesting these beliefs are malleable, exposure to images of a racially diverse (vs. nondiverse) environmental organization in an embedded randomized experiment reduced the perceived gap between whites' and nonwhites' environmental concerns and strengthened associations between nonwhites and the category "environmentalists" among minority respondents. These findings suggest that stereotypes about others' environmental attitudes may pose a barrier to broadening public engagement with environmental initiatives, particularly among populations most vulnerable to negative environmental impacts.}, } @article {pmid30373834, year = {2018}, author = {Chen, W and Jin, Y and Zhao, J and Liu, N and Cui, Y}, title = {Nickel-hydrogen batteries for large-scale energy storage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11694-11699}, pmid = {30373834}, issn = {1091-6490}, abstract = {Large-scale energy storage is of significance to the integration of renewable energy into electric grid. Despite the dominance of pumped hydroelectricity in the market of grid energy storage, it is limited by the suitable site selection and footprint impact. Rechargeable batteries show increasing interests in the large-scale energy storage; however, the challenging requirement of low-cost materials with long cycle and calendar life restricts most battery chemistries for use in the grid storage. Recently we introduced a concept of manganese-hydrogen battery with Mn2+/MnO2 redox cathode paired with H+/H2 gas anode, which has a long life of 10,000 cycles and with potential for grid energy storage. Here we expand this concept by replacing Mn2+/MnO2 redox with a nickel-based cathode, which enables ∼10× higher areal capacity loading, reaching ∼35 mAh cm-2 We also replace high-cost Pt catalyst on the anode with a low-cost, bifunctional nickel-molybdenum-cobalt alloy, which could effectively catalyze hydrogen evolution and oxidation reactions in alkaline electrolyte. Such a nickel-hydrogen battery exhibits an energy density of ∼140 Wh kg-1 (based on active materials) in aqueous electrolyte and excellent rechargeability with negligible capacity decay over 1,500 cycles. The estimated cost of the nickel-hydrogen battery based on active materials reaches as low as ∼$83 per kilowatt-hour, demonstrating attractive characteristics for large-scale energy storage.}, } @article {pmid30373833, year = {2018}, author = {Dutta, DJ and Woo, DH and Lee, PR and Pajevic, S and Bukalo, O and Huffman, WC and Wake, H and Basser, PJ and SheikhBahaei, S and Lazarevic, V and Smith, JC and Fields, RD}, title = {Regulation of myelin structure and conduction velocity by perinodal astrocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11832-11837}, pmid = {30373833}, issn = {1091-6490}, support = {ZIA HD000713/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/*physiology ; Axons/metabolism ; Humans ; Mice ; Mice, Transgenic ; Myelin Sheath/metabolism/*physiology ; Nerve Fibers, Myelinated/physiology ; Neural Conduction/physiology ; Neuroglia/metabolism ; Optic Nerve/metabolism ; Ranvier's Nodes/metabolism ; Structure-Activity Relationship ; Thrombin ; Vesicle-Associated Membrane Protein 2 ; }, abstract = {The speed of impulse transmission is critical for optimal neural circuit function, but it is unclear how the appropriate conduction velocity is established in individual axons. The velocity of impulse transmission is influenced by the thickness of the myelin sheath and the morphology of electrogenic nodes of Ranvier along axons. Here we show that myelin thickness and nodal gap length are reversibly altered by astrocytes, glial cells that contact nodes of Ranvier. Thrombin-dependent proteolysis of a cell adhesion molecule that attaches myelin to the axon (neurofascin 155) is inhibited by vesicular release of thrombin protease inhibitors from perinodal astrocytes. Transgenic mice expressing a dominant-negative fragment of VAMP2 in astrocytes, to reduce exocytosis by 50%, exhibited detachment of adjacent paranodal loops of myelin from the axon, increased nodal gap length, and thinning of the myelin sheath in the optic nerve. These morphological changes alter the passive cable properties of axons to reduce conduction velocity and spike-time arrival in the CNS in parallel with a decrease in visual acuity. All effects were reversed by the thrombin inhibitor Fondaparinux. Similar results were obtained by viral transfection of tetanus toxin into astrocytes of rat corpus callosum. Previously, it was unknown how the myelin sheath could be thinned and the functions of perinodal astrocytes were not well understood. These findings describe a form of nervous system plasticity in which myelin structure and conduction velocity are adjusted by astrocytes. The thrombin-dependent cleavage of neurofascin 155 may also have relevance to myelin disruption and repair.}, } @article {pmid30373832, year = {2018}, author = {Kohn, MJ and Castro, AE and Kerswell, BC and Ranero, CR and Spear, FS}, title = {Shear heating reconciles thermal models with the metamorphic rock record of subduction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11706-11711}, pmid = {30373832}, issn = {1091-6490}, abstract = {Some commonly referenced thermal-mechanical models of current subduction zones imply temperatures that are 100-500 °C colder at 30-80-km depth than pressure-temperature conditions determined thermobarometrically from exhumed metamorphic rocks. Accurately inferring subduction zone thermal structure, whether from models or rocks, is crucial for predicting metamorphic reactions and associated fluid release, subarc melting conditions, rheologies, and fault-slip phenomena. Here, we compile surface heat flow data from subduction zones worldwide and show that values are higher than can be explained for a frictionless subduction interface often assumed for modeling. An additional heat source--likely shear heating--is required to explain these forearc heat flow values. A friction coefficient of at least 0.03 and possibly as high as 0.1 in some cases explains these data, and we recommend a provisional average value of 0.05 ± 0.015 for modeling. Even small coefficients of friction can contribute several hundred degrees of heating at depths of 30-80 km. Adding such shear stresses to thermal models quantitatively reproduces the pressure-temperature conditions recorded by exhumed metamorphic rocks. Comparatively higher temperatures generally drive rock dehydration and densification, so, at a given depth, hotter rocks are denser than colder rocks, and harder to exhume through buoyancy mechanisms. Consequently--conversely to previous proposals--exhumed metamorphic rocks might overrepresent old-cold subduction where rocks at the slab interface are wetter and more buoyant than in young-hot subduction zones.}, } @article {pmid30373831, year = {2018}, author = {Carraro, L and Hartikainen, H and Jokela, J and Bertuzzo, E and Rinaldo, A}, title = {Estimating species distribution and abundance in river networks using environmental DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11724-11729}, pmid = {30373831}, issn = {1091-6490}, mesh = {Animal Distribution/classification ; Animals ; Biodiversity ; Biomass ; Computer Simulation ; DNA/*analysis ; Ecosystem ; Environmental Biomarkers/*genetics ; Hydrology/*methods ; Models, Theoretical ; Rivers ; Specimen Handling/methods ; }, abstract = {All organisms leave traces of DNA in their environment. This environmental DNA (eDNA) is often used to track occurrence patterns of target species. Applications are especially promising in rivers, where eDNA can integrate information about populations upstream. The dispersion of eDNA in rivers is modulated by complex processes of transport and decay through the dendritic river network, and we currently lack a method to extract quantitative information about the location and density of populations contributing to the eDNA signal. Here, we present a general framework to reconstruct the upstream distribution and abundance of a target species across a river network, based on observed eDNA concentrations and hydro-geomorphological features of the network. The model captures well the catchment-wide spatial biomass distribution of two target species: a sessile invertebrate (the bryozoan Fredericella sultana) and its parasite (the myxozoan Tetracapsuloides bryosalmonae). Our method is designed to easily integrate general biological and hydrological data and to enable spatially explicit estimates of the distribution of sessile and mobile species in fluvial ecosystems based on eDNA sampling.}, } @article {pmid30373830, year = {2018}, author = {Kersten, RD and Weng, JK}, title = {Gene-guided discovery and engineering of branched cyclic peptides in plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10961-E10969}, pmid = {30373830}, issn = {1091-6490}, mesh = {Amino Acid Sequence/genetics ; Biological Products/chemistry ; Gene Expression Profiling/*methods ; *Genes, Plant ; Genome ; Genomics/methods ; Lignans/biosynthesis ; Peptides/chemistry/genetics ; Peptides, Cyclic/*genetics/metabolism ; Plants/*genetics ; Protein Processing, Post-Translational ; Ribosomes/genetics/metabolism ; }, abstract = {The plant kingdom contains vastly untapped natural product chemistry, which has been traditionally explored through the activity-guided approach. Here, we describe a gene-guided approach to discover and engineer a class of plant ribosomal peptides, the branched cyclic lyciumins. Initially isolated from the Chinese wolfberry Lycium barbarum, lyciumins are protease-inhibiting peptides featuring an N-terminal pyroglutamate and a macrocyclic bond between a tryptophan-indole nitrogen and a glycine α-carbon. We report the identification of a lyciumin precursor gene from L. barbarum, which encodes a BURP domain and repetitive lyciumin precursor peptide motifs. Genome mining enabled by this initial finding revealed rich lyciumin genotypes and chemotypes widespread in flowering plants. We establish a biosynthetic framework of lyciumins and demonstrate the feasibility of producing diverse natural and unnatural lyciumins in transgenic tobacco. With rapidly expanding plant genome resources, our approach will complement bioactivity-guided approaches to unlock and engineer hidden plant peptide chemistry for pharmaceutical and agrochemical applications.}, } @article {pmid30373829, year = {2018}, author = {Lin, YC and Wang, J and Delhomme, N and Schiffthaler, B and Sundström, G and Zuccolo, A and Nystedt, B and Hvidsten, TR and de la Torre, A and Cossu, RM and Hoeppner, MP and Lantz, H and Scofield, DG and Zamani, N and Johansson, A and Mannapperuma, C and Robinson, KM and Mähler, N and Leitch, IJ and Pellicer, J and Park, EJ and Van Montagu, M and Van de Peer, Y and Grabherr, M and Jansson, S and Ingvarsson, PK and Street, NR}, title = {Functional and evolutionary genomic inferences in Populus through genome and population sequencing of American and European aspen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10970-E10978}, pmid = {30373829}, issn = {1091-6490}, mesh = {Biological Evolution ; DNA, Plant/genetics ; Evolution, Molecular ; Genetic Variation ; Genetics, Population/methods ; Genome, Plant ; Genomics ; Linkage Disequilibrium/genetics ; Phylogeny ; Populus/*genetics ; Selection, Genetic/genetics ; Sequence Analysis, DNA/methods ; Trees/genetics ; }, abstract = {The Populus genus is one of the major plant model systems, but genomic resources have thus far primarily been available for poplar species, and primarily Populus trichocarpa (Torr. & Gray), which was the first tree with a whole-genome assembly. To further advance evolutionary and functional genomic analyses in Populus, we produced genome assemblies and population genetics resources of two aspen species, Populus tremula L. and Populus tremuloides Michx. The two aspen species have distributions spanning the Northern Hemisphere, where they are keystone species supporting a wide variety of dependent communities and produce a diverse array of secondary metabolites. Our analyses show that the two aspens share a similar genome structure and a highly conserved gene content with P. trichocarpa but display substantially higher levels of heterozygosity. Based on population resequencing data, we observed widespread positive and negative selection acting on both coding and noncoding regions. Furthermore, patterns of genetic diversity and molecular evolution in aspen are influenced by a number of features, such as expression level, coexpression network connectivity, and regulatory variation. To maximize the community utility of these resources, we have integrated all presented data within the PopGenIE web resource (PopGenIE.org).}, } @article {pmid30373828, year = {2018}, author = {Bausch-Fluck, D and Goldmann, U and Müller, S and van Oostrum, M and Müller, M and Schubert, OT and Wollscheid, B}, title = {The in silico human surfaceome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10988-E10997}, pmid = {30373828}, issn = {1091-6490}, mesh = {Cell Membrane/*metabolism/physiology ; Computer Simulation ; Databases, Chemical ; Forecasting/*methods ; Humans ; Machine Learning ; Membrane Proteins/*metabolism/physiology ; Proteome/metabolism ; Proteomics/methods ; }, abstract = {Cell-surface proteins are of great biomedical importance, as demonstrated by the fact that 66% of approved human drugs listed in the DrugBank database target a cell-surface protein. Despite this biomedical relevance, there has been no comprehensive assessment of the human surfaceome, and only a fraction of the predicted 5,000 human transmembrane proteins have been shown to be located at the plasma membrane. To enable analysis of the human surfaceome, we developed the surfaceome predictor SURFY, based on machine learning. As a training set, we used experimentally verified high-confidence cell-surface proteins from the Cell Surface Protein Atlas (CSPA) and trained a random forest classifier on 131 features per protein and, specifically, per topological domain. SURFY was used to predict a human surfaceome of 2,886 proteins with an accuracy of 93.5%, which shows excellent overlap with known cell-surface protein classes (i.e., receptors). In deposited mRNA data, we found that between 543 and 1,100 surfaceome genes were expressed in cancer cell lines and maximally 1,700 surfaceome genes were expressed in embryonic stem cells and derivative lines. Thus, the surfaceome diversity depends on cell type and appears to be more dynamic than the nonsurface proteome. To make the predicted surfaceome readily accessible to the research community, we provide visualization tools for intuitive interrogation (wlab.ethz.ch/surfaceome). The in silico surfaceome enables the filtering of data generated by multiomics screens and supports the elucidation of the surfaceome nanoscale organization.}, } @article {pmid30373827, year = {2018}, author = {Pande, K and Donatelli, JJ and Malmerberg, E and Foucar, L and Bostedt, C and Schlichting, I and Zwart, PH}, title = {Ab initio structure determination from experimental fluctuation X-ray scattering data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11772-11777}, pmid = {30373827}, issn = {1091-6490}, support = {R01 GM109019/GM/NIGMS NIH HHS/United States ; }, mesh = {Chlorella ; Crystallography, X-Ray/*methods/statistics & numerical data ; Photoelectron Spectroscopy/*methods/statistics & numerical data ; Radiography/statistics & numerical data ; Research Design ; Scattering, Radiation ; X-Ray Diffraction ; X-Rays ; }, abstract = {Fluctuation X-ray scattering (FXS) is an emerging experimental technique in which X-ray solution scattering data are collected from particles in solution using ultrashort X-ray exposures generated by a free-electron laser (FEL). FXS experiments overcome the low data-to-parameter ratios associated with traditional solution scattering measurements by providing several orders of magnitude more information in the final processed data. Here we demonstrate the practical feasibility of FEL-based FXS on a biological multiple-particle system and describe data-processing techniques required to extract robust FXS data and significantly reduce the required number of snapshots needed by introducing an iterative noise-filtering technique. We showcase a successful ab initio electron density reconstruction from such an experiment, studying the Paramecium bursaria Chlorella virus (PBCV-1).}, } @article {pmid30373826, year = {2018}, author = {Kosack, S and Coscia, M and Smith, E and Albrecht, K and Barabási, AL and Hausmann, R}, title = {Functional structures of US state governments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11748-11753}, pmid = {30373826}, issn = {1091-6490}, abstract = {Governments in modern societies undertake an array of complex functions that shape politics and economics, individual and group behavior, and the natural, social, and built environment. How are governments structured to execute these diverse responsibilities? How do those structures vary, and what explains the differences? To examine these longstanding questions, we develop a technique for mapping Internet "footprint" of government with network science methods. We use this approach to describe and analyze the diversity in functional scale and structure among the 50 US state governments reflected in the webpages and links they have created online: 32.5 million webpages and 110 million hyperlinks among 47,631 agencies. We first verify that this extensive online footprint systematically reflects known characteristics: 50 hierarchically organized networks of state agencies that scale with population and are specialized around easily identifiable functions in accordance with legal mandates. We also find that the footprint reflects extensive diversity among these state functional hierarchies. We hypothesize that this variation should reflect, among other factors, state income, economic structure, ideology, and location. We find that government structures are most strongly associated with state economic structures, with location and income playing more limited roles. Voters' recent ideological preferences about the proper roles and extent of government are not significantly associated with the scale and structure of their state governments as reflected online. We conclude that the online footprint of governments offers a broad and comprehensive window on how they are structured that can help deepen understanding of those structures.}, } @article {pmid30373825, year = {2018}, author = {Freeman, BG and Scholer, MN and Ruiz-Gutierrez, V and Fitzpatrick, JW}, title = {Climate change causes upslope shifts and mountaintop extirpations in a tropical bird community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11982-11987}, pmid = {30373825}, issn = {1091-6490}, mesh = {Altitude ; Animal Distribution/*physiology ; Animal Migration/physiology ; Animals ; Biodiversity ; Birds/*physiology ; Climate Change ; Conservation of Natural Resources ; Ecosystem ; Extinction, Biological ; Forecasting ; Homing Behavior ; Peru ; Population Dynamics/*trends ; Temperature ; Tropical Climate ; }, abstract = {Montane species worldwide are shifting upslope in response to recent temperature increases. These upslope shifts are predicted to lead to mountaintop extinctions of species that live only near mountain summits, but empirical examples of populations that have disappeared are sparse. We show that recent warming constitutes an "escalator to extinction" for birds on a remote Peruvian mountain-high-elevation species have declined in both range size and abundance, and several previously common mountaintop residents have disappeared from the local community. Our findings support projections that warming will likely drive widespread extirpations and extinctions of high-elevation taxa in the tropical Andes. Such climate change-driven mountaintop extirpations may be more likely in the tropics, where temperature seems to exert a stronger control on species' range limits than in the temperate zone. In contrast, we show that lowland bird species at our study site are expanding in range size as they shift their upper limits upslope and may thus benefit from climate change.}, } @article {pmid30373824, year = {2018}, author = {Wang, J and Ho, WY and Lim, K and Feng, J and Tucker-Kellogg, G and Nave, KA and Ling, SC}, title = {Cell-autonomous requirement of TDP-43, an ALS/FTD signature protein, for oligodendrocyte survival and myelination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10941-E10950}, pmid = {30373824}, issn = {1091-6490}, mesh = {Amyotrophic Lateral Sclerosis/*metabolism/pathology ; Animals ; DNA-Binding Proteins/genetics/*metabolism ; Disease Models, Animal ; Female ; Frontotemporal Dementia/*metabolism/pathology ; Gray Matter/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Motor Neurons/cytology/metabolism ; Myelin Sheath/genetics/*metabolism ; Nerve Fibers, Myelinated/metabolism ; Neuroglia/cytology/metabolism ; Oligodendroglia/cytology/*metabolism ; Spinal Cord/metabolism ; White Matter/metabolism ; }, abstract = {TDP-43 aggregates in neurons and glia are the defining pathological hallmark of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), raising the possibility of glial damage in the disease pathogenesis. However, the normal physiological functions of TDP-43 in glia are largely unknown. To address how TDP-43 may be required for oligodendroglial functions we selectively deleted TDP-43 in mature oligodendrocytes in mice. Although mice with TDP-43 deleted in oligodendrocytes are born in an expected Mendelian ratio, they develop progressive neurological phenotypes leading to early lethality accompanied by a progressive reduction in myelination. The progressive myelin reduction is likely due to a combination of the cell-autonomous RIPK1-mediated necroptosis of mature oligodendrocytes and the TDP-43-dependent reduction in the expression of myelin genes. Strikingly, enhanced proliferation of NG2-positive oligodendrocyte precursor cells within the white matter, but not the gray matter, was able to replenish the loss of mature oligodendrocytes, indicating an intrinsic regeneration difference between the gray and white matter oligodendrocytes. By contrast, there was no loss of spinal cord motor neurons and no sign of denervation at the neuromuscular synapses. Taken together, our data demonstrate that TDP-43 is indispensable for oligodendrocyte survival and myelination, and loss of TDP-43 in oligodendrocytes exerts no apparent toxicity on motor neurons.}, } @article {pmid30373823, year = {2018}, author = {Abbasi, I and Trancoso Lopo de Queiroz, A and Kirstein, OD and Nasereddin, A and Horwitz, BZ and Hailu, A and Salah, I and Mota, TF and Fraga, DBM and Veras, PST and Poche, D and Poche, R and Yeszhanov, A and Brodskyn, C and Torres-Poche, Z and Warburg, A}, title = {Plant-feeding phlebotomine sand flies, vectors of leishmaniasis, prefer Cannabis sativa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11790-11795}, pmid = {30373823}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal ; Cannabis ; Female ; Herbivory/*physiology ; Insect Vectors/parasitology ; Leishmania/genetics ; Leishmaniasis/microbiology ; Male ; Psychodidae/metabolism/parasitology/*physiology ; Sex Factors ; }, abstract = {Blood-sucking phlebotomine sand flies (Diptera: Psychodidae) transmit leishmaniasis as well as arboviral diseases and bartonellosis. Sand fly females become infected with Leishmania parasites and transmit them while imbibing vertebrates' blood, required as a source of protein for maturation of eggs. In addition, both females and males consume plant-derived sugar meals as a source of energy. Plant meals may comprise sugary solutions such as nectar or honeydew (secreted by plant-sucking homopteran insects), as well as phloem sap that sand flies obtain by piercing leaves and stems with their needle-like mouthparts. Hence, the structure of plant communities can influence the distribution and epidemiology of leishmaniasis. We designed a next-generation sequencing (NGS)-based assay for determining the source of sand fly plant meals, based upon the chloroplast DNA gene ribulose bisphosphate carboxylase large chain (rbcL). Here, we report on the predilection of several sand fly species, vectors of leishmaniasis in different parts of the world, for feeding on Cannabis sativa We infer this preference based on the substantial percentage of sand flies that had fed on C. sativa plants despite the apparent "absence" of these plants from most of the field sites. We discuss the conceivable implications of the affinity of sand flies for C. sativa on their vectorial capacity for Leishmania and the putative exploitation of their attraction to C. sativa for the control of sand fly-borne diseases.}, } @article {pmid30373822, year = {2018}, author = {Jiang, P and Sun, K and Tong, YK and Cheng, SH and Cheng, THT and Heung, MMS and Wong, J and Wong, VWS and Chan, HLY and Chan, KCA and Lo, YMD and Chiu, RWK}, title = {Preferred end coordinates and somatic variants as signatures of circulating tumor DNA associated with hepatocellular carcinoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10925-E10933}, pmid = {30373822}, issn = {1091-6490}, mesh = {Adult ; Biomarkers, Tumor/blood/genetics ; Carcinoma, Hepatocellular/blood/*genetics/surgery ; Circulating Tumor DNA/blood/*genetics ; DNA, Neoplasm/blood/genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Liver Neoplasms/blood/*genetics/surgery ; Liver Transplantation ; Male ; Middle Aged ; Mutation ; }, abstract = {Circulating tumor-derived cell-free DNA (ctDNA) analysis offers an attractive noninvasive means for detection and monitoring of cancers. Evidence for the presence of cancer is dependent on the ability to detect features in the peripheral circulation that are deemed as cancer-associated. We explored approaches to improve the chance of detecting the presence of cancer based on sequence information present on ctDNA molecules. We developed an approach to detect the total pool of somatic mutations. We then investigated if there existed a class of ctDNA signature in the form of preferred plasma DNA end coordinates. Cell-free DNA fragmentation is a nonrandom process. Using plasma samples obtained from liver transplant recipients, we showed that liver contributed cell-free DNA molecules ended more frequently at certain genomic coordinates than the nonliver-derived molecules. The abundance of plasma DNA molecules with these liver-associated ends correlated with the liver DNA fractions in the plasma samples. Studying the DNA end characteristics in plasma of patients with hepatocellular carcinoma and chronic hepatitis B, we showed that there were millions of tumor-associated plasma DNA end coordinates in the genome. Abundance of plasma DNA molecules with tumor-associated DNA ends correlated with the tumor DNA fractions even in plasma samples of hepatocellular carcinoma patients that were subjected to shallow-depth sequencing analysis. Plasma DNA end coordinates may therefore serve as hallmarks of ctDNA that could be sampled readily and, hence, may improve the cost-effectiveness of liquid biopsy assessment.}, } @article {pmid30373821, year = {2018}, author = {Liu, B and Li, Y and Stackpole, EE and Novak, A and Gao, Y and Zhao, Y and Zhao, X and Richter, JD}, title = {Regulatory discrimination of mRNAs by FMRP controls mouse adult neural stem cell differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {E11397-E11405}, pmid = {30373821}, issn = {1091-6490}, support = {R01 MH080434/MH/NIMH NIH HHS/United States ; R21 NS095632/NS/NINDS NIH HHS/United States ; U54 HD082013/HD/NICHD NIH HHS/United States ; U54 HD090256/HD/NICHD NIH HHS/United States ; R01 MH078972/MH/NIMH NIH HHS/United States ; R01 NS079415/NS/NINDS NIH HHS/United States ; }, abstract = {Fragile X syndrome (FXS) is caused by the loss of fragile X mental retardation protein (FMRP), an RNA binding protein whose deficiency impacts many brain functions, including differentiation of adult neural stem cells (aNSCs). However, the mechanism by which FMRP influences these processes remains unclear. Here, we performed ribosome profiling and transcriptomic analysis of aNSCs in parallel from wild-type and Fmr1 knockout mice. Our data revealed diverse gene expression changes at both mRNA and translation levels. Many mitosis and neurogenesis genes were dysregulated primarily at the mRNA level, while numerous synaptic genes were mostly dysregulated at the translation level. Translational "buffering", whereby changes in ribosome association with mRNA are compensated by alterations in RNA abundance, was also evident. Knockdown of NECDIN, an FMRP-repressed transcriptional factor, rescued neuronal differentiation. In addition, we discovered that FMRP regulates mitochondrial mRNA expression and energy homeostasis. Thus, FMRP controls diverse transcriptional and posttranscriptional gene expression programs critical for neural differentiation.}, } @article {pmid30373820, year = {2018}, author = {Hedges, SB and Cohen, WB and Timyan, J and Yang, Z}, title = {Haiti's biodiversity threatened by nearly complete loss of primary forest.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11850-11855}, pmid = {30373820}, issn = {1091-6490}, mesh = {Amphibians ; Animal Distribution/physiology ; Animals ; Biodiversity ; Climate Change ; Conservation of Natural Resources/economics/*statistics & numerical data ; Ecosystem ; *Extinction, Biological ; *Forests ; Haiti ; Humans ; Reptiles ; Tropical Climate ; }, abstract = {Tropical forests hold most of Earth's biodiversity. Their continued loss through deforestation and agriculture is the main threat to species globally, more than disease, invasive species, and climate change. However, not all tropical forests have the same ability to sustain biodiversity. Those that have been disturbed by humans, including forests previously cleared and regrown (secondary growth), have lower levels of species richness compared with undisturbed (primary) forests. The difference is even greater considering extinctions that will later emanate from the disturbance (extinction debt). Here, we find that Haiti has less than 1% of its original primary forest and is therefore among the most deforested countries. Primary forest has declined over three decades inside national parks, and 42 of the 50 highest and largest mountains have lost all primary forest. Our surveys of vertebrate diversity (especially amphibians and reptiles) on mountaintops indicates that endemic species have been lost along with the loss of forest. At the current rate, Haiti will lose essentially all of its primary forest during the next two decades and is already undergoing a mass extinction of its biodiversity because of deforestation. These findings point to the need, in general, for better reporting of forest cover data of relevance to biodiversity, instead of "total forest" as defined by the United Nation's Food and Agricultural Organization. Expanded detection and monitoring of primary forest globally will improve the efficiency of conservation measures, inside and outside of protected areas.}, } @article {pmid30373819, year = {2018}, author = {Yuan, R and Lee, J and Su, HW and Levy, E and Khudiyev, T and Voldman, J and Fink, Y}, title = {Microfluidics in structured multimaterial fibers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10830-E10838}, pmid = {30373819}, issn = {1091-6490}, support = {R21 EB022729/EB/NIBIB NIH HHS/United States ; U24 AI118656/AI/NIAID NIH HHS/United States ; }, mesh = {Cell Separation ; Equipment Design/methods ; Hydrodynamics ; Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques/*methods ; Microfluidics/*instrumentation/*methods ; }, abstract = {Traditional fabrication techniques for microfluidic devices utilize a planar chip format that possesses limited control over the geometry of and materials placement around microchannel cross-sections. This imposes restrictions on the design of flow fields and external forces (electric, magnetic, piezoelectric, etc.) that can be imposed onto fluids and particles. Here we report a method of fabricating microfluidic channels with complex cross-sections. A scaled-up version of a microchannel is dimensionally reduced through a thermal drawing process, enabling the fabrication of meters-long microfluidic fibers with nonrectangular cross-sectional shapes, such as crosses, five-pointed stars, and crescents. In addition, by codrawing compatible materials, conductive domains can be integrated at arbitrary locations along channel walls. We validate this technology by studying unexplored regimes in hydrodynamic flow and by designing a high-throughput cell separation device. By enabling these degrees of freedom in microfluidic device design, fiber microfluidics provides a method to create microchannel designs that are inaccessible using planar techniques.}, } @article {pmid30373818, year = {2018}, author = {Cook, DM and Bennett, M and Friedman, B and Lawrimore, J and Yeh, E and Bloom, K}, title = {Fork pausing allows centromere DNA loop formation and kinetochore assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11784-11789}, pmid = {30373818}, issn = {1091-6490}, support = {R37 GM032238/GM/NIGMS NIH HHS/United States ; T32 CA201159/CA/NCI NIH HHS/United States ; }, mesh = {Cell Cycle Proteins ; Centromere/genetics/*physiology ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone ; DNA/metabolism ; DNA Damage/physiology ; DNA Repair/physiology ; DNA Replication/*physiology ; Kinetochores/metabolism/*physiology ; Phleomycins ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Spindle Apparatus/metabolism ; Thermodynamics ; }, abstract = {De novo kinetochore assembly, but not template-directed assembly, is dependent on COMA, the kinetochore complex engaged in cohesin recruitment. The slowing of replication fork progression by treatment with phleomycin (PHL), hydroxyurea, or deletion of the replication fork protection protein Csm3 can activate de novo kinetochore assembly in COMA mutants. Centromere DNA looping at the site of de novo kinetochore assembly can be detected shortly after exposure to PHL. Using simulations to explore the thermodynamics of DNA loops, we propose that loop formation is disfavored during bidirectional replication fork migration. One function of replication fork stalling upon encounters with DNA damage or other blockades may be to allow time for thermal fluctuations of the DNA chain to explore numerous configurations. Biasing thermodynamics provides a mechanism to facilitate macromolecular assembly, DNA repair, and other nucleic acid transactions at the replication fork. These loop configurations are essential for sister centromere separation and kinetochore assembly in the absence of the COMA complex.}, } @article {pmid30373817, year = {2018}, author = {Gemechu, Y and Millrine, D and Hashimoto, S and Prakash, J and Sanchenkova, K and Metwally, H and Gyanu, P and Kang, S and Kishimoto, T}, title = {Humanized cereblon mice revealed two distinct therapeutic pathways of immunomodulatory drugs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11802-11807}, pmid = {30373817}, issn = {1091-6490}, mesh = {Animals ; Humans ; Ikaros Transcription Factor/drug effects/metabolism ; Immunologic Factors/metabolism ; Immunomodulation/*drug effects/*physiology ; Mice ; Models, Animal ; Nerve Tissue Proteins/*drug effects/genetics/metabolism/physiology ; Peptide Hydrolases/genetics/metabolism ; Proteolysis/drug effects ; Substrate Specificity ; Ubiquitin-Protein Ligases/metabolism ; }, abstract = {Immunomodulatory drugs (IMiDs), including thalidomide derivatives such as lenalidomide and pomalidomide, offer therapeutic benefit in several hematopoietic malignancies and autoimmune/inflammatory diseases. However, it is difficult to study the IMiD mechanism of action in murine disease models because murine cereblon (CRBN), the substrate receptor for IMiD action, is resistant to some of IMiDs therapeutic effects. To overcome this difficulty, we generated humanized cereblon (CRBNI391V) mice thereby providing an animal model to unravel complex mechanisms of action in a murine physiological setup. In our current study, we investigated the degradative effect toward IKZF1 and CK-1α, a target substrate of IMiDs. Unlike WT mice which were resistant to lenalidomide and pomalidomide, T lymphocytes from CRBNI391V mice responded with a higher degree of IKZF1 and CK-1α protein degradation. Furthermore, IMiDs resulted in an increase in IL-2 among CRBNI391V mice but not in the WT group. We have also tested a thalidomide derivative, FPFT-2216, which showed an inhibitory effect toward IKZF1 protein level. As opposed to pomalidomide, FPFT-2216 and lenalidomide degrades CK-1α. Additionally, we assessed the potential therapeutic effects of IMiDs in dextran sodium sulfate (DSS)-induced colitis. In both WT and humanized mice, lenalidomide showed a significant therapeutic effect in the DSS model of colitis, while the effect of pomalidomide was less pronounced. Thus, while IMiDs' degradative effect on IKZF1 and CK-1α, and up-regulation of IL-2, is dependent on CRBN, the therapeutic benefit of IMiDs in a mouse model of inflammatory bowel disease occurs through a CRBN-IMiD binding region independent pathway.}, } @article {pmid30373816, year = {2018}, author = {Morgan, MG and Overgaard, M and Bowles, AE}, title = {The varied careers of Kenneth L. Bowles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {49}, pages = {12326-12330}, doi = {10.1073/pnas.1816519115}, pmid = {30373816}, issn = {1091-6490}, } @article {pmid30373815, year = {2018}, author = {Zhang, M and Wen, B and Anton, OM and Yao, Z and Dubois, S and Ju, W and Sato, N and DiLillo, DJ and Bamford, RN and Ravetch, JV and Waldmann, TA}, title = {IL-15 enhanced antibody-dependent cellular cytotoxicity mediated by NK cells and macrophages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10915-E10924}, pmid = {30373815}, issn = {1091-6490}, support = {N01CO12400/CA/NCI NIH HHS/United States ; }, mesh = {Alemtuzumab/administration & dosage ; Animals ; Antibodies, Monoclonal/immunology ; Antibody-Dependent Cell Cytotoxicity/drug effects/*immunology ; Antineoplastic Combined Chemotherapy Protocols/*pharmacology ; Cell Line, Tumor ; Female ; Humans ; Interleukin-15/*administration & dosage/immunology ; Killer Cells, Natural/drug effects/*immunology ; Macrophages/drug effects/*immunology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, SCID ; Rituximab/administration & dosage ; }, abstract = {The goal of cancer immunotherapy is to stimulate the host immune system to attack malignant cells. Antibody-dependent cellular cytotoxicity (ADCC) is a pivotal mechanism of antitumor action of clinically employed antitumor antibodies. IL-15 administered to patients with metastatic malignancy by continuous i.v. infusion at 2 μg/kg/d for 10 days was associated with a 38-fold increase in the number and activation status of circulating natural killer (NK) cells and activation of macrophages which together are ADCC effectors. We investigated combination therapy of IL-15 with rituximab in a syngeneic mouse model of lymphoma transfected with human CD20 and with alemtuzumab (Campath-1H) in a xenograft model of human adult T cell leukemia (ATL). IL-15 greatly enhanced the therapeutic efficacy of both rituximab and alemtuzumab in tumor models. The additivity/synergy was shown to be associated with augmented ADCC. Both NK cells and macrophages were critical elements in the chain of interacting effectors involved in optimal therapeutic responses mediated by rituximab with IL-15. We provide evidence supporting the hypothesis that NK cells interact with macrophages to augment the NK-cell activation and expression of FcγRIV and the capacity of these cells to become effectors of ADCC. The present study supports clinical trials of IL-15 combined with tumor-directed monoclonal antibodies.}, } @article {pmid30373814, year = {2018}, author = {Kreiner, CT and Nielsen, TH and Serena, BL}, title = {Role of income mobility for the measurement of inequality in life expectancy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11754-11759}, pmid = {30373814}, issn = {1091-6490}, mesh = {Databases, Factual ; Denmark ; Female ; *Health Status Disparities ; Humans ; Income/statistics & numerical data ; Life Expectancy/*ethnology ; Male ; Models, Theoretical ; Mortality ; Poverty/statistics & numerical data ; Social Class ; Socioeconomic Factors ; }, abstract = {This work proposes a method to compute the income gradient in period life expectancy that accounts for income mobility. Using income and mortality records of the Danish population over the period 1980-2013, we validate the method and provide estimates of the income gradient. The period life expectancy of individuals at a certain age, and belonging to a certain income class, is normally computed by using the mortality of older cohorts in the same income class. This approach does not take into account that a substantial fraction of the population moves away from their original income class, which leads to an upward bias in the estimation of the income gradient in life expectancy. For 40-y-olds in the bottom 5% of the income distribution, the risk of dying before age 60 is overestimated by 25%. For the top 5% income class, the risk of dying is underestimated by 20%. By incorporating a classic approach from the social mobility literature, we provide a method that predicts income mobility and future mortality simultaneously. With this method, the association between income and life expectancy is lower throughout the income distribution. Without accounting for income mobility, the estimated difference in life expectancy between persons in percentiles 20 and 80 in the income distribution is 4.6 y for males and 4.1 y for females, while it is only half as big when accounting for mobility. The estimated rise in life-expectancy inequality over time is also halved when accounting for income mobility.}, } @article {pmid30373813, year = {2018}, author = {Viaud, S and Ma, JSY and Hardy, IR and Hampton, EN and Benish, B and Sherwood, L and Nunez, V and Ackerman, CJ and Khialeeva, E and Weglarz, M and Lee, SC and Woods, AK and Young, TS}, title = {Switchable control over in vivo CAR T expansion, B cell depletion, and induction of memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10898-E10906}, pmid = {30373813}, issn = {1091-6490}, support = {R01 CA208398/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD19/immunology ; B-Lymphocytes/immunology ; Bioengineering/*methods ; Cytokines/metabolism ; Cytotoxicity, Immunologic/immunology ; Female ; Immunoglobulin Switch Region/genetics/immunology ; Immunotherapy, Adoptive/*methods ; Lymphocyte Activation/physiology ; Mice ; Mice, Inbred C57BL ; Models, Animal ; Models, Biological ; Receptors, Antigen, T-Cell/metabolism ; T-Lymphocytes/immunology ; }, abstract = {Chimeric antigen receptor (CAR) T cells with a long-lived memory phenotype are correlated with durable, complete remissions in patients with leukemia. However, not all CAR T cell products form robust memory populations, and those that do can induce chronic B cell aplasia in patients. To address these challenges, we previously developed a switchable CAR (sCAR) T cell system that allows fully tunable, on/off control over engineered cellular activity. To further evaluate the platform, we generated and assessed different murine sCAR constructs to determine the factors that afford efficacy, persistence, and expansion of sCAR T cells in a competent immune system. We find that sCAR T cells undergo significant in vivo expansion, which is correlated with potent antitumor efficacy. Most importantly, we show that the switch dosing regimen not only allows control over B cell populations through iterative depletion and repopulation, but that the "rest" period between dosing cycles is the key for induction of memory and expansion of sCAR T cells. These findings introduce rest as a paradigm in enhancing memory and improving the efficacy and persistence of engineered T cell products.}, } @article {pmid30373812, year = {2018}, author = {Li, Y and Jiang, J and Liu, W and Wang, H and Zhao, L and Liu, S and Li, P and Zhang, S and Sun, C and Wu, Y and Yu, S and Li, X and Zhang, H and Qian, H and Zhang, D and Guo, F and Zhai, Q and Ding, Q and Wang, L and Ying, H}, title = {microRNA-378 promotes autophagy and inhibits apoptosis in skeletal muscle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10849-E10858}, pmid = {30373812}, issn = {1091-6490}, mesh = {3-Phosphoinositide-Dependent Protein Kinases/metabolism ; Animals ; Apoptosis/physiology ; Autophagy/physiology ; Autophagy-Related Protein-1 Homolog/metabolism ; Caspase 9/metabolism ; Forkhead Box Protein O1/genetics/metabolism ; Male ; Mice ; Mice, Knockout ; MicroRNAs/genetics/*physiology ; Muscle Cells/metabolism ; Muscle, Skeletal/cytology/metabolism/*physiology ; Running ; Signal Transduction ; Stress, Physiological ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {The metabolic regulation of cell death is sophisticated. A growing body of evidence suggests the existence of multiple metabolic checkpoints that dictate cell fate in response to metabolic fluctuations. However, whether microRNAs (miRNAs) are able to respond to metabolic stress, reset the threshold of cell death, and attempt to reestablish homeostasis is largely unknown. Here, we show that miR-378/378* KO mice cannot maintain normal muscle weight and have poor running performance, which is accompanied by impaired autophagy, accumulation of abnormal mitochondria, and excessive apoptosis in skeletal muscle, whereas miR-378 overexpression is able to enhance autophagy and repress apoptosis in skeletal muscle of mice. Our in vitro data show that metabolic stress-responsive miR-378 promotes autophagy and inhibits apoptosis in a cell-autonomous manner. Mechanistically, miR-378 promotes autophagy initiation through the mammalian target of rapamycin (mTOR)/unc-51-like autophagy activating kinase 1 (ULK1) pathway and sustains autophagy via Forkhead box class O (FoxO)-mediated transcriptional reinforcement by targeting phosphoinositide-dependent protein kinase 1 (PDK1). Meanwhile, miR-378 suppresses intrinsic apoptosis initiation directly through targeting an initiator caspase-Caspase 9. Thus, we propose that miR-378 is a critical component of metabolic checkpoints, which integrates metabolic information into an adaptive response to reduce the propensity of myocytes to undergo apoptosis by enhancing the autophagic process and blocking apoptotic initiation. Lastly, our data suggest that inflammation-induced down-regulation of miR-378 might contribute to the pathogenesis of muscle dystrophy.}, } @article {pmid30373680, year = {2018}, author = {Nyoni, AM and Chiwaridzo, M and Tadyanemhandu, C and January, J and Dambi, JM}, title = {Profiling the mental health of diabetic patients: a cross-sectional survey of Zimbabwean patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {772}, pmid = {30373680}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Aged ; Comorbidity ; Cross-Sectional Studies ; Diabetes Mellitus/*epidemiology ; Diabetes Mellitus, Type 2/epidemiology ; Female ; Humans ; Male ; Mental Disorders/*epidemiology ; Middle Aged ; *Quality of Life ; *Social Support ; *Socioeconomic Factors ; Zimbabwe ; }, abstract = {OBJECTIVE: The burden of diabetes mellitus has exponentially increased in low resource settings. Patients with diabetes are more likely to exhibit poor mental health which negatively affects treatment outcomes. However, patients with high levels of social support (SS) are likely to report optimal mental health. We sought to determine how SS affects the report of psychiatric morbidity and health-related quality of life (HRQoL) in 108 diabetic patients in Harare, Zimbabwe.

RESULTS: The average age of participants was 54.1 (SD 18.6) years. Most of the participants were; females (69.4%), married (51.9%), and were of low level of income (43.5%). 37.1% of the participants exhibited signs of psychiatric morbidity [mean Shona Symptoms Questionnaire score-6.7 (SD 3.2)]. Further, patients also reported lower HRQoL [mean EQ-5D-VAS score-64.1 (SD 15.3)] and high levels of SS [mean Multidimensional Scale of Perceived Social Support score-43.7 (SD 11.5)]. Patients who received greater amount of SS had optimal mental health. Being female, unmarried, lower education attainment, having more comorbid conditions, being diagnosed with type 2 diabetes and having been diagnosed of diabetes for a longer duration were associated with poorer mental health. It is important to develop context-specific interventions to improve diabetic patients' mental health.}, } @article {pmid30373673, year = {2018}, author = {Cannon, MV and Bogale, H and Rutt, L and Humphrys, M and Korpe, P and Duggal, P and Ravel, J and Serre, D}, title = {A high-throughput sequencing assay to comprehensively detect and characterize unicellular eukaryotes and helminths from biological and environmental samples.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {195}, pmid = {30373673}, issn = {2049-2618}, support = {R25 GM055036/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Several of the most devastating human diseases are caused by eukaryotic parasites transmitted by arthropod vectors or through food and water contamination. These pathogens only represent a fraction of all unicellular eukaryotes and helminths that are present in the environment and many uncharacterized organisms might have subtle but pervasive effects on health, including by modifying the microbiome where they reside. Unfortunately, while we have modern molecular tools to characterize bacterial and, to a lesser extent, fungal communities, we lack suitable methods to comprehensively investigate and characterize most unicellular eukaryotes and helminths: the detection of these organisms often relies on microscopy that cannot differentiate related organisms, while molecular assays can only detect the pathogens specifically tested.

RESULTS: Here, we describe a novel sequencing-based assay, akin to bacterial 16S rRNA sequencing, that enables high-throughput detection and characterization of a wide range of unicellular eukaryotes and helminths, including those from taxonomical groups containing all common human parasites. We designed and evaluated taxon-specific PCR primer pairs that selectively amplify all species from eight taxonomical groups (Apicomplexa, Amoeba, Diplomonadida, Kinetoplastida, Parabasalia, Nematoda, Platyhelminthes, and Microsporidia). We then used these primers to screen DNA extracted from clinical, biological, and environmental samples, and after next-generation sequencing, identified both known and previously undescribed organisms from most taxa targeted.

CONCLUSIONS: This novel high-throughput assay enables comprehensive detection and identification of eukaryotic parasites and related organisms, from a wide range of complex biological and environmental samples. This approach can be easily deployed to many settings and will efficiently complement existing methods and provide a holistic perspective on the microbiome.}, } @article {pmid30373668, year = {2018}, author = {Gebretsadik, D and Metaferia, Y and Seid, A and Fenta, GM and Gedefie, A}, title = {Prevalence of intestinal parasitic infection among children under 5 years of age at Dessie Referral Hospital: cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {771}, pmid = {30373668}, issn = {1756-0500}, mesh = {Child ; Child, Preschool ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Hospitals/statistics & numerical data ; Humans ; Infant ; Intestinal Diseases, Parasitic/diagnosis/*epidemiology ; Male ; Prevalence ; }, abstract = {OBJECTIVE: Intestinal parasitic infection is a serious public health problem throughout the world particularly in developing countries. Like other countries in sub saran region epidemiological data regarding prevalence of intestinal parasites and their associated factors were limited in Ethiopia. So, the main objective of this study was to determine the prevalence of intestinal parasites and associated factors among under five children in Dessie Referral Hospital from August 1, 2017 to December 20, 2017.

RESULTS: In this research a total of 232 under five children were involved. Out of these study subjects 36 (15.5%) were infected with at least one intestinal parasites. A total of five intestinal parasites were examined and the dominant parasite was E. histolytica 15/232 (6.5%) followed by H. nana 11/232 (4.7%). All age groups were affected by intestinal parasites but children who were at the age of below 2 years and at the age between 2 and 3 years were 4.7 times and 2.6 times at risk of acquiring infection with intestinal parasites in comparison at the age of 3-5 years children.}, } @article {pmid30373667, year = {2018}, author = {Krishnaiah, S and Ramanathan, RV}, title = {Impact of blindness due to cataract in elderly fallers: findings from a cross-sectional study in Andhra Pradesh, South India.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {773}, pmid = {30373667}, issn = {1756-0500}, mesh = {Accidental Falls/prevention & control/*statistics & numerical data ; Aged ; Aged, 80 and over ; Blindness/*epidemiology/etiology ; Cataract/complications/*epidemiology ; Cataract Extraction ; Cross-Sectional Studies ; Female ; Humans ; India/epidemiology ; Male ; Middle Aged ; }, abstract = {OBJECTIVE: To estimate the prevalence of falls, frequency of falls, injury due to falls and to explore the relationship between cataract-related blindness and falls in older patients above or equal to 50 years of age.

RESULTS: A cross-sectional study was conducted to investigate the relationship between cataract related blindness and risk of fall. Details about any fall in the previous 12 months and systemic illness history were collected through a personal interview. Overall, 70 (18.3%; 95% confidence intervals (CI) 14.4%, 22.2%) of the 382 patients investigated had experienced falls. The history of recurrent falls were more commonly seen in patients with bilateral cataract (p = 0.023). The mean presenting Logarithm of the Minimum Angle of Resolution (LogMAR) visual acuity was significantly higher in fallers when compared to non-fallers: 0.81 ± 0.41 versus 0.65 ± 0.31 (p = 0.001). The prevalence of falls was significantly higher in patients with bilateral cataract blind; adjusted odds ratio (OR): 1.76 (p = 0.042). Timely diagnosis and surgical intervention in patients with bilateral blindness due to cataract may help prevent falls in older patients in Andhra Pradesh, South India.}, } @article {pmid30373663, year = {2018}, author = {Herath, HMMTB and Withana, M and Gamage, R and Rodrigo, C}, title = {Is there a delay in seeking medical care after the first seizure in "resource limited settings": a pilot study from Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {774}, pmid = {30373663}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Epilepsy/*diagnosis/*therapy ; Female ; Humans ; Male ; Middle Aged ; Patient Acceptance of Health Care/*statistics & numerical data ; Pilot Projects ; Seizures/*diagnosis/*therapy ; Sri Lanka ; Time-to-Treatment/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVES: Current guidelines suggest that patients presenting with the first seizure should be assessed by a specialist, preferably with investigations such as electroencephalography and imaging to reach a definitive diagnosis. We conducted a cross sectional study among patients with confirmed epilepsy, at a tertiary level neurology clinic in Sri Lanka with the aim of assessing delays in first contact with a medical doctor and in performing key investigations after the first seizure.

RESULTS: Majority had sought medical attention within 24 h of the first seizure (71.2%) and had seen a specialist within the 1st week since the seizure (61%). Also a significant proportion had completed key investigations such as electroencephalography (63.2%) and brain imaging within a month (51%) since the first medical consultation. Of many socio-demographic and illness related factors examined, only a non-generalized tonic-clonic presentation was significantly associated with delay in seeking medical help.}, } @article {pmid30373660, year = {2018}, author = {Tozaki, T and Karasawa, K and Minamijima, Y and Ishii, H and Kikuchi, M and Kakoi, H and Hirota, KI and Kusano, K and Nagata, SI}, title = {Detection of phosphorothioated (PS) oligonucleotides in horse plasma using a product ion (m/z 94.9362) derived from the PS moiety for doping control.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {770}, pmid = {30373660}, issn = {1756-0500}, support = {Japan Racing Association (2017-2019)//Japan Racing Association/ ; }, mesh = {Animals ; Blood Chemical Analysis/*veterinary ; Chromatography, Liquid ; *Doping in Sports ; *Genetic Therapy ; Horses/*blood ; Phosphorothioate Oligonucleotides/*blood ; Plasma/*chemistry ; Tandem Mass Spectrometry ; }, abstract = {OBJECTIVE: Clinical research on gene therapy has advanced the field of veterinary medicine, and gene doping, which is the illegal use of gene therapy, has become a major concern in horseracing. Since the International Federation of Horseracing Authorities defined the administration of oligonucleotides and its analogues as a genetic therapy in 2017, the development of therapeutic nucleotide-detection techniques has become an urgent need. Most currently marketed and developed oligonucleotide therapeutics for humans consist of modified nucleotides to increase stability, and phosphorothioate (PS) modification is common.

RESULTS: We demonstrated the specific detection of phosphorothioated oligonucleotides (PSOs) using LC/MS/MS. PSOs produce the specific product ion (m/z 94.9362) derived from PS moiety. PS is not derived from endogenous substances in animal body, and the product ion is a suitable marker for the detection of PSOs. With our strategy, reproducible target analyses were achieved for identifying the specific substances, with a LOD of 0.1 ng/mL and a quantification rage of 0.1-200 ng/mL in deproteinated plasma. Non-target analyses could also detect the presence of PSOs selectively with 100 ng/mL in the same matrix. These results suggested that the detection of PSOs in horse blood is possible by targeting the product ion using LC/MS/MS.}, } @article {pmid30373649, year = {2018}, author = {Elliott, RM and Burrell, AR and Harrigan, PW and Murgo, M and Rolls, KD and Sibbritt, DW and Iredell, JR and Elliott, D}, title = {Antimicrobial prescription patterns and ventilator associated pneumonia: findings from a 10-site prospective audit.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {769}, pmid = {30373649}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Drug Prescriptions/*statistics & numerical data ; Female ; Humans ; Incidence ; Intensive Care Units/*statistics & numerical data ; Male ; Medical Audit/statistics & numerical data ; Middle Aged ; Pneumonia, Ventilator-Associated/*epidemiology ; Practice Patterns, Physicians'/*statistics & numerical data ; Prevalence ; Prospective Studies ; }, abstract = {OBJECTIVE: To examine anti-microbial prescribing practices associated with ventilator-associated pneumonia from data gathered during an audit of practice and outcomes in intensive care units (ICUs) in a previously published study.

RESULTS: The patient sample of 169 was 65% male with an average age of 59.7 years, a mean APACHE II score of 20.6, and a median ICU stay of 11 days. While ventilator-associated pneumonia was identified using a specific 4-item checklist in 29 patients, agreement between the checklist and independent physician diagnosis was only 17%. Sputum microbe culture reporting was sparse. Approximately 75% of the sample was administered an antimicrobial (main indications: lung infection [54%] and prophylaxis [11%]). No clinical justification was documented for 20% of prescriptions. Piperacillin/tazobactam was most frequently prescribed (1/3rd of all antimicrobial prescriptions) with about half of those for prophylaxis. Variations in prescribing practices were identified, including apparent gaps in antimicrobial stewardship; particularly in relation to prescribing for prophylaxis and therapy de-escalation. Sputum microbe culture reports for VAP did not appear to contribute to prescribing decisions but physician suspicion of lung infection and empiric therapy rather than ventilator-associated pneumonia criteria and guideline concordance.}, } @article {pmid30373642, year = {2018}, author = {Ja'afar, JN and Bhore, SJ and Phua, KK}, title = {Non-specificity of sequence characterised amplified region as an alternative molecular epidemiology marker for the identification of Salmonella enterica subspecies enterica serovar Typhi.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {766}, pmid = {30373642}, issn = {1756-0500}, support = {1001/CIPPM/844078//Universiti Sains Malaysia (MY)/ ; 1001/PSKBP/86300111//Universiti Sains Malaysia/ ; }, mesh = {Bacterial Typing Techniques/*standards ; *Biomarkers ; Humans ; Malaysia ; Random Amplified Polymorphic DNA Technique/*standards ; *Salmonella typhi ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Identification of Salmonella Typhi by conventional culture techniques is labour-intensive, time consuming, and lack sensitivity and specificity unlike high-throughput epidemiological markers that are highly specific but are not affordable for low-resource settings. SCAR, obtained from RAPD technique, is an affordable, reliable and reproducible method for developing genetic markers. Hence, this study investigated the use of SCAR as an alternative molecular epidemiological marker for easy identification of S. Typhi in low-resource settings.

RESULTS: One hundred and twenty RAPD primers were screened through RAPD-PCR against a panel of common enterobacteriaceae for the best RAPD band pattern discrimination to develop SCAR primers that were used to develop a RAPD-SCAR PCR. Of this number, 10 were selected based on their calculated indices of discrimination. Four RAPD primers, SBSA02, SBSA03, SBSD08 and SBSD11 produced suitable bands ranging from 900 to 2500 bp. However, only SBSD11 was found to be specific for S. Typhi, and was cloned, sequenced and used to design new SCAR primers. The primers were used to amplify a panel of organisms to evaluate its specificity. However, the amplified regions were similar to other non-Typhi genomes denoting a lack of specificity of the primers as a marker for S. Typhi.}, } @article {pmid30373634, year = {2018}, author = {Belachew, A and Tewabe, T and Asmare, A and Hirpo, D and Zeleke, B and Muche, D}, title = {Prevalence of exclusive breastfeeding practice and associated factors among mothers having infants less than 6 months old, in Bahir Dar, Northwest, Ethiopia: a community based cross sectional study, 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {768}, pmid = {30373634}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Breast Feeding/*statistics & numerical data ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Humans ; Infant ; Infant, Newborn ; Mothers/*statistics & numerical data ; Prevalence ; Young Adult ; }, abstract = {BACKGROUND: Breast milk provides all the energy and nutrients that the infant needs for the first 6 months of life. Suboptimal breastfeeding especially lacks exclusive breastfeeding increase risk of severe acute malnutrition by 3.2-fold and major contributory factor for infant child mortality. Therefore, the objective of this study was to assess the prevalence of exclusive breastfeeding practice and associated factors among mothers having infants less than 6 months old in Bahir Dar city, Northwest, Ethiopia, 2017.

RESULT: The prevalence of exclusive breastfeeding practice 1 day before the survey was 86.4%. Mothers who; have young infant aged 0-1 month old [AOR = 5.702 (1.747, 18.613)], house wife [AOR = 2.995 (1.557, 5.690)] and are not influenced by culture [AOR = 11 (3.449, 35.165)] were more likely to practice exclusive breastfeeding than their counterparts.}, } @article {pmid30373632, year = {2018}, author = {Smyth, LJ and Maxwell, AP and Benson, KA and Kilner, J and McKay, GJ and McKnight, AJ}, title = {Validation of differentially methylated microRNAs identified from an epigenome-wide association study; Sanger and next generation sequencing approaches.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {767}, pmid = {30373632}, issn = {1756-0500}, mesh = {CpG Islands ; *DNA Methylation ; Diabetic Nephropathies/*genetics ; Epigenesis, Genetic/*genetics ; *Genome-Wide Association Study ; *High-Throughput Nucleotide Sequencing ; Humans ; Ireland ; MicroRNAs/*genetics ; Polymorphism, Single Nucleotide ; United Kingdom ; }, abstract = {OBJECTIVES: Altered DNA methylation and microRNA profiles are associated with diabetic kidney disease. This study compared different sequencing approaches to define the genetic and epigenetic architecture of sequences surrounding microRNAs associated with diabetic kidney disease.

RESULTS: We compared Sanger and next generation sequencing to validate microRNAs associated with diabetic kidney disease identified from an epigenome-wide association study (EWAS). These microRNAs demonstrated differential methylation levels in cases with diabetic kidney disease compared to controls with long duration of type 1 diabetes and no evidence of kidney disease (Padjusted < 10-5). Targeted next generation sequencing analysis of genomic DNA and matched cell-line transformed DNA samples identified four genomic variants within the microRNAs, two within miR-329-2 and two within miR-429. Sanger sequencing of genomic DNA replicated these findings and confirmed the altered methylation status of the CpG sites identified by the EWAS in bisulphite-treated DNA. This investigation successfully fine-mapped the genetic sequence around key microRNAs. Variants have been detected which may affect their methylation status and methylated CpG sites have been confirmed. Additionally, we explored both the fidelity of next generation sequencing analysis and the potential efficacy of cell-line transformed DNA samples in place of finite patient samples in discovery genetic and epigenetic research.}, } @article {pmid30373594, year = {2018}, author = {Cao, YF and Wang, SF and Li, X and Zhang, YL and Qiao, YJ}, title = {The anticancer mechanism investigation of Tanshinone IIA by pharmacological clustering in protein network.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {90}, pmid = {30373594}, issn = {1752-0509}, abstract = {BACKGROUND: Cancer is the second most common cause of death globally. The anticancer effects of Tanshinone IIA (Tan IIA) has been confirmed by numerous researches. However, the underlying mechanism remained to be integrated in systematic format. Systems biology embraced the complexity of cancer; therefore, a system study approach was proposed in the present study to explore the anticancer mechanism of Tan IIA based on network pharmacology.

METHOD: Agilent Literature Search (ALS), a text-mining tool, was used to pull protein targets of Tan IIA. Then, pharmacological clustering was applied to classify obtained hits, the anticancer module was analysed further. The top ten essential nodes in the anticancer module were obtained by ClusterONE. Functional units in the anticancer module were catalogued and validated by Gene Ontology (GO) analysis. Meanwhile, KEGG and Cell Signalling Technology Pathway were employed to provide pathway data for potential anticancer pathways construction. Finally, the pathways were plotted using Cytoscape 3.5.1. Furthermore, in vitro experiments with five carcinoma cell lines were conducted.

RESULTS: A total of 258 proteins regulated by Tan IIA were identified through ALS and were visualized by protein network. Pharmacological clustering further sorted 68 proteins that intimately involved in cancer pathogenesis based on Gene Ontology. Subsequently, pathways on anticancer effect of Tan IIA were delineated. Five functional units were clarified according to literature: including regulation on apoptosis, proliferation, sustained angiogenesis, autophagic cell death, and cell cycle. The GO analysis confirmed the classification was statistically significant. The inhibiting influence of Tan IIA on p70 S6K/mTOR pathway was revealed for the first time. The in vitro experiments displayed the selectivity of Tan IIA on HeLa, MDA-MB-231, HepG2, A549, and ACHN cell lines, the IC50 values were 0.54 μM, 4.63 μM, 1.42 μM, 17.30 μM and 204.00 μM, respectively. This result further reinforced the anticancer effect of Tan IIA treatment.

CONCLUSIONS: The current study provides a systematic methodology for discovering the coordination of the anticancer pathways regulated by Tan IIA via protein network. And it also offers a valuable guidance for systematic study on the therapeutic values of other herbs and their active compounds.}, } @article {pmid30373569, year = {2018}, author = {Dec, M and Nowaczek, A and Stępień-Pyśniak, D and Wawrzykowski, J and Urban-Chmiel, R}, title = {Identification and antibiotic susceptibility of lactobacilli isolated from turkeys.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {168}, pmid = {30373569}, issn = {1471-2180}, support = {2017/01/X/NZ8/00478//Narodowe Centrum Nauki/ ; }, abstract = {BACKGROUND: The aim of this study was to identify Lactobacillus isolates derived from turkeys from six Polish farms and to characterize their phenotypic and genotypic antibiotic resistance profiles.

RESULTS: Among 62 isolates identified by MALDI-TOF mass spectrometry and restriction analysis of 16S rDNA, the dominant species was L. salivarius (35%), followed by L. crispatus (21%), L. ingluviei (14.5%) and L. johnsonii (10%). A high prevalence of resistance to tetracycline (68% resistant isolates), lincomycin (64.5%) and enrofloxacin (60%) among the lactobacilli tested was observed. Fewer than 50% isolates were resistant to ampicillin (47%), erythromycin (45%), streptomycin (31%), chloramphenicol (29%) and gentamicin (10%). As many as 64,5% of the isolates showed multidrug resistance. High MIC values for ampicillin (≥64 μg/ml) were usually accompanied by elevated MICs for cephalosporins (≥16 μg/ml) and high MICs for tiamulin, i.e. ≥32 μg/ml, were noted in most of the turkey lactobacilli (61%). The occurrence of resistance genes was associated with phenotypic resistance, with the exception of five phenotypically susceptible isolates that contained the tetM, tetL, ermC, ermB or cat genes. The most frequently identified were ermB (45% isolates), tetL (40%), tetW (37%) and tetM (29%), and the occurrence of lnuA (18%), cat (10%), ermC (6%), ant(6)-Ia (5%) and aadE (5%) was less frequent. The mechanism of ampicillin resistance has not been elucidated, but the results of nitrocefin test confirmed that it is not involved in the production of beta-lactamases.

CONCLUSIONS: The high rate of antibiotic resistance observed in this study indicates the need to implement the principles of rational use of antibiotics in poultry. The presence of transmissible resistant genes in lactobacilli may contribute to the development of antibiotic resistant pathogenic strains that pose a threat to both poultry and consumers. The results of these studies may be useful for committees providing guidance on antibiotic susceptibility of microorganisms in order to revise and supplement current microbiological cut-offs values within the genus Lactobacillus.}, } @article {pmid30373534, year = {2018}, author = {Wang, P and Gao, L and Hu, Y and Li, F}, title = {Feature related multi-view nonnegative matrix factorization for identifying conserved functional modules in multiple biological networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {394}, pmid = {30373534}, issn = {1471-2105}, support = {61532014//National Natural Science Foundation of China/ ; 61432010//National Natural Science Foundation of China/ ; 61702397//National Natural Science Foundation of China/ ; }, mesh = {*Algorithms ; Cluster Analysis ; Computational Biology/*methods ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; Neoplasms/*genetics/metabolism ; *Protein Interaction Maps ; }, abstract = {BACKGROUND: Comprehensive analyzing multi-omics biological data in different conditions is important for understanding biological mechanism in system level. Multiple or multi-layer network model gives us a new insight into simultaneously analyzing these data, for instance, to identify conserved functional modules in multiple biological networks. However, because of the larger scale and more complicated structure of multiple networks than single network, how to accurate and efficient detect conserved functional biological modules remains a significant challenge.

RESULTS: Here, we propose an efficient method, named ConMod, to discover conserved functional modules in multiple biological networks. We introduce two features to characterize multiple networks, thus all networks are compressed into two feature matrices. The module detection is only performed in the feature matrices by using multi-view non-negative matrix factorization (NMF), which is independent of the number of input networks. Experimental results on both synthetic and real biological networks demonstrate that our method is promising in identifying conserved modules in multiple networks since it improves the accuracy and efficiency comparing with state-of-the-art methods. Furthermore, applying ConMod to co-expression networks of different cancers, we find cancer shared gene modules, the majority of which have significantly functional implications, such as ribosome biogenesis and immune response. In addition, analyzing on brain tissue-specific protein interaction networks, we detect conserved modules related to nervous system development, mRNA processing, etc. CONCLUSIONS: ConMod facilitates finding conserved modules in any number of networks with a low time and space complexity, thereby serve as a valuable tool for inference shared traits and biological functions of multiple biological system.}, } @article {pmid30373533, year = {2018}, author = {Yao, Y and Jin, Z and Lee, JH}, title = {An improved statistical model for taxonomic assignment of metagenomics.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {98}, pmid = {30373533}, issn = {1471-2156}, support = {R03 AG054186/AG/NIA NIH HHS/United States ; R56 AG051876/AG/NIA NIH HHS/United States ; AG054186//National Institutes of Health/ ; AG051876//National Institute on Aging/ ; }, abstract = {BACKGROUND: With the advances in the next-generation sequencing technologies, researchers can now rapidly examine the composition of samples from humans and their surroundings. To enhance the accuracy of taxonomy assignments in metagenomic samples, we developed a method that allows multiple mismatch probabilities from different genomes.

RESULTS: We extended the algorithm of taxonomic assignment of metagenomic sequence reads (TAMER) by developing an improved method that can set a different mismatch probability for each genome rather than imposing a single parameter for all genomes, thereby obtaining a greater degree of accuracy. This method, which we call TADIP (Taxonomic Assignment of metagenomics based on DIfferent Probabilities), was comprehensively tested in simulated and real datasets. The results support that TADIP improved the performance of TAMER especially in large sample size datasets with high complexity.

CONCLUSIONS: TADIP was developed as a statistical model to improve the estimate accuracy of taxonomy assignments. Based on its varying mismatch probability setting and correlated variance matrix setting, its performance was enhanced for high complexity samples when compared with TAMER.}, } @article {pmid30373532, year = {2018}, author = {Lai, YC and Liang, YC and Jiang, TX and Widelitz, RB and Wu, P and Chuong, CM}, title = {Transcriptome analyses of reprogrammed feather / scale chimeric explants revealed co-expressed epithelial gene networks during organ specification.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {780}, pmid = {30373532}, issn = {1471-2164}, support = {R01 AR047364/AR/NIAMS NIH HHS/United States ; R01 AR060306/AR/NIAMS NIH HHS/United States ; AR47364//National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; AR60306//National Institute of Arthritis and Musculoskeletal and Skin Diseases/ ; }, abstract = {BACKGROUND: The molecular mechanism controlling regional specific skin appendage phenotypes is a fundamental question that remains unresolved. We recently identified feather and scale primordium associated genes and with functional studies, proposed five major modules are involved in scale-to-feather conversion and their integration is essential to form today's feathers. Yet, how the molecular networks are wired and integrated at the genomic level is still unknown.

RESULTS: Here, we combine classical recombination experiments and systems biology technology to explore the molecular mechanism controlling cell fate specification. In the chimeric explant, dermal fate is more stable, while epidermal fate is reprogrammed to be similar to the original appendage type of the mesenchyme. We analyze transcriptome changes in both scale-to-feather and feather-to-scale transition in the epidermis. We found a highly interconnected regulatory gene network controlling skin appendage types. These gene networks are organized around two molecular hubs, β-catenin and retinoic acid (RA), which can bind to regulatory elements controlling downstream gene expression, leading to scale or feather fates. ATAC sequencing analyses revealed about 1000 altered widely distributed chromatin open sites. We find that perturbation of a key gene alters the expression of many other co-expressed genes in the same module.

CONCLUSIONS: Our findings suggest that these feather / scale fate specification genes form an interconnected network and rewiring of the gene network can lead to changes of appendage phenotypes, acting similarly to endogenous reprogramming at the tissue level. This work shows that key hub molecules, β-catenin and retinoic acid, regulate scale / feather fate specification gene networks, opening up new possibilities to understand the switches controlling organ phenotypes in a two component (epithelial and mesenchyme) system.}, } @article {pmid30373531, year = {2018}, author = {Hou, Q and Huang, Y and Liu, Y and Luo, Y and Wang, B and Deng, R and Zhang, S and Liu, F and Chen, D}, title = {Profiling the miRNA-mRNA-lncRNA interaction network in MSC osteoblast differentiation induced by (+)-cholesten-3-one.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {783}, pmid = {30373531}, issn = {1471-2164}, support = {2017A030312009//Natural Science Foundation of Guangdong Province/ ; 2017M612641//China Postdoctoral Science Foundation/ ; 20181095//Guangdong Provincial Traditional Chinese Medicine Research Project/ ; 20182043//Guangdong Provincial Traditional Chinese Medicine Research Project/ ; }, abstract = {BACKGROUND: Our previous study showed that (+)-cholesten-3-one (CN) has the potential to induce the osteoblastic differentiation of mesenchymal stem cells (MSCs). However, the roles of CN in targeting miRNA-mRNA-lncRNA interactions to regulate osteoblast differentiation remain poorly understood.

RESULTS: A total of 77 miRNAs (36 upregulated and 41 downregulated) and 295 lncRNAs (281 upregulated and 14 downregulated) were significantly differentially expressed during CN-induced MSC osteogenic differentiation. Bioinformatic analysis identified that several pathways may play vital roles in MSC osteogenic differentiation, such as the vitamin D receptor signalling, TNF signalling, PI3K-Akt signalling, calcium signalling, and mineral absorption pathways. Further bioinformatic analysis revealed 16 core genes, including 6 mRNAs (Vdr, Mgp, Fabp3, Fst, Cd38, and Col1a1), 5 miRNAs (miR-483, miR-298, miR-361, miR-92b and miR-155) and 5 lncRNAs (NR_046246.1, NR_046239.1, XR_086062.1, XR_145872.1 and XR_146737.1), that may play important roles in regulating the CN-induced osteogenic differentiation of MSCs. Verified by the luciferase reporter, AR-S, qRT-PCR and western blot assays, we identified one miRNA (miR-298) that may enhance the osteogenic differentiation potential of MSCs via the vitamin D receptor signalling pathway.

CONCLUSIONS: This study revealed the global expression profile of miRNAs and lncRNAs involved in the Chinese medicine active ingredient CN-induced osteoblast differentiation of MSCs for the first time and provided a foundation for future investigations of miRNA-mRNA-lncRNA interaction networks to completely illuminate the regulatory role of CN in MSC osteoblast differentiation.}, } @article {pmid30373525, year = {2018}, author = {Lu, Y and Feng, Z and Liu, X and Bian, L and Xie, H and Zhang, C and Mysore, KS and Liang, J}, title = {MiR393 and miR390 synergistically regulate lateral root growth in rice under different conditions.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {261}, pmid = {30373525}, issn = {1471-2229}, support = {31271623//National Natural Science Foundation of China/ ; }, mesh = {Abscisic Acid/metabolism/pharmacology ; Droughts ; Gene Expression Regulation, Plant/drug effects ; Indoleacetic Acids/metabolism ; Metals, Heavy/toxicity ; MicroRNAs/*genetics ; Oryza/drug effects/*genetics/*growth & development ; Plant Roots/genetics/*growth & development ; Plants, Genetically Modified ; RNA, Plant/genetics ; }, abstract = {BACKGROUND: Plants have evolved excellent ability of flexibly regulating the growth of organs to adapt to changing environment, for example, the modulation of lateral root development in response to environmental stresses. Despite of fundamental discovery that some microRNAs are involved in this process, the molecular mechanisms of how these microRNAs work together are still largely unknown.

RESULTS: Here we show that miR390 induced by auxin promotes lateral root growth in rice. However, this promotion can be suppressed by miR393, which is induced by various stresses and ABA (Abscisic Acid). Results that miR393 responded to ABA stronger and earlier than other stresses implied that ABA likely is authentic factor for inducing miR393. The transgenic lines respectively over-expressing miR393 and OsTAS3a (Oryza sativa Trans-Acting Short RNA precursor 3a) displayed opposite phenotypes in lateral root growth. MiR390 was found to be dominantly expressed at lateral root primordia and roots tips while miR393 mainly expressed in the base part of roots at very low level. When miR393 was up-regulated by various stresses, miR390 expression level fell down. However, the risen expression level of miR390 induced by auxin didn't affect the expression of miR393 and its target OsTIR1 (Transport Inhibitor Response 1). Together with analysis of the two transgenic lines, we provide a model of how the growth of lateral roots in rice is regulated distinctively by the 2 microRNAs.

CONCLUSION: We propose that miR390 induced by auxin triggers the lateral root growth under normal growth conditions, meanwhile miR393 just lurks as a potentially regulative role; Once plants suffer from stresses, miR393 will be induced to negatively regulate miR390-mediated growth of lateral roots in rice.}, } @article {pmid30373523, year = {2018}, author = {Thomas, SR and Leung, S and Knox, K and Wilkinson, TMA and Staples, KJ and Lestrate, P and Wauters, D and Gorringe, A and Taylor, SC}, title = {Development of flow cytometric opsonophagocytosis and antibody-mediated complement deposition assays for non-typeable Haemophilus influenzae.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {167}, pmid = {30373523}, issn = {1471-2180}, abstract = {BACKGROUND: Haemophilus influenzae is found in the nasopharynx of 80% of the human population. While colonisation with non-typeable Haemophilus influenzae (NTHi) is usually asymptomatic, it is capable of causing acute and chronic otitis media (OM) in infants, invasive disease in susceptible groups and is the leading cause of exacerbations of patients with chronic obstructive pulmonary disease (COPD). Current methods for assessing functional antibody immunity to NTHi are limited and labour intensive. Flow cytometric assays could provide an attractive alternative to evaluate immune responses to candidate vaccines in clinical trials.

RESULTS: We have developed a duplexed flow-cytometric uptake and oxidative burst opsonophagocytosis assay (fOPA). We have also developed a duplexed antibody-mediated complement C3b/iC3b and C5b-9 deposition assay (CDA). Antibody-mediated C3b/iC3b deposition correlated with opsonophagocytic uptake (r = 0.65) and with opsonophagocytic oxidative burst (r = 0.69). Both fOPA and CDA were reproducible, with the majority of samples giving a coefficient of variation (CV) of < 20% and overall assay CVs of 14% and 16% respectively.

CONCLUSIONS: The high-throughput flow cytometric assays developed here were successfully optimised for use with NTHi. Assays proved to be sensitive and highly reproducible for the measurement of bacterial uptake and oxidative burst opsonophagocytosis and antibody-mediated deposition of C3b/iC3b and C5b-9. These assays are useful tools for use in large scale epidemiological studies and to assist in the assessment of functional antibody induced by NTHi candidate vaccines.}, } @article {pmid30373521, year = {2018}, author = {Luo, M and Wang, L and Zhu, W and Fu, J and Song, F and Fang, M and Dong, J and Dong, Z}, title = {Identification and characterization of skin color microRNAs in Koi carp (Cyprinus carpio L.) by Illumina sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {779}, pmid = {30373521}, issn = {1471-2164}, support = {BRA2017083//"333 project" training fund project of Jiangsu province/ ; KYCX18_0738//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) are endogenous, small (21-25 nucleotide), non-coding RNAs that play important roles in numerous biological processes. Koi carp exhibit diverse color patterns, making it an ideal subject for studying the genetics of pigmentation. However, the influence of miRNAs on skin color regulation and variation in Koi carp is poorly understood.

RESULTS: Herein, we performed small RNA (sRNA) analysis of the three main skin colors in Koi carp by Illumina sequencing. The results revealed 330, 397, and 335 conserved miRNAs (belonging to 81 families) and 340, 353, and 351 candidate miRNAs in black, red, and white libraries, respectively. A total of 164 differentially expressed miRNAs (DEMs) and 14 overlapping DEMs were identified, including miR-196a, miR-125b, miR-202, miR-205-5p, miR-200b, and etc. Target prediction and functional analysis of color-related miRNAs such as miR-200b, miR-206, and miR-196a highlighted putative target genes, including Mitf, Mc1r, Foxd3, and Sox10 that are potentially related to pigmentation. Determination of reference miRNAs for relative quantification showed that let-7a was the most abundant single reference gene, and let-7a and miR-26b was the most abundant combination.

CONCLUSIONS: The findings provide novel insight into the molecular mechanisms determining skin color differentiation in Koi carp, and serve as a valuable reference for future studies on tissue-specific miRNA abundance in Koi carp.}, } @article {pmid30373517, year = {2018}, author = {Mediati, DG and Burke, CM and Ansari, S and Harry, EJ and Duggin, IG}, title = {High-throughput sequencing of sorted expression libraries reveals inhibitors of bacterial cell division.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {781}, pmid = {30373517}, issn = {1471-2164}, support = {FT160100010//Australian Research Council/ ; }, abstract = {BACKGROUND: Bacterial filamentation occurs when rod-shaped bacteria grow without dividing. To identify genetically encoded inhibitors of division that promote filamentation, we used cell sorting flow cytometry to enrich filamentous clones from an inducible expression library, and then identified the cloned DNA with high-throughput DNA sequencing. We applied the method to an expression library made from fragmented genomic DNA of uropathogenic E. coli UTI89, which undergoes extensive reversible filamentation in urinary tract infections and might encode additional regulators of division.

RESULTS: We identified 55 genomic regions that reproducibly caused filamentation when expressed from the plasmid vector, and then further localized the cause of filamentation in several of these to specific genes or sub-fragments. Many of the identified genomic fragments encode genes that are known to participate in cell division or its regulation, and others may play previously-unknown roles. Some of the prophage genes identified were previously implicated in cell division arrest. A number of the other fragments encoded potential short transcripts or peptides.

CONCLUSIONS: The results provided evidence of potential new links between cell division and distinct cellular processes including central carbon metabolism and gene regulation. Candidate regulators of the UTI-associated filamentation response or others were identified amongst the results. In addition, some genomic fragments that caused filamentation may not have evolved to control cell division, but may have applications as artificial inhibitors. Our approach offers the opportunity to carry out in depth surveys of diverse DNA libraries to identify new genes or sequences encoding the capacity to inhibit division and cause filamentation.}, } @article {pmid30373515, year = {2018}, author = {Park, J and Belden, WJ}, title = {Long non-coding RNAs have age-dependent diurnal expression that coincides with age-related changes in genome-wide facultative heterochromatin.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {777}, pmid = {30373515}, issn = {1471-2164}, support = {R01 GM101378/GM/NIGMS NIH HHS/United States ; GM101378//National Institute of General Medical Sciences/ ; NE1439//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: Disrupted diurnal rhythms cause accelerated aging and an increased incidence in age-related disease and morbidity. The circadian clock governs cell physiology and metabolism by controlling transcription and chromatin. The goal of this study is to further understand the mechanism of age-related changes to circadian chromatin with a focus on facultative heterochromatin and diurnal non-coding RNAs.

RESULTS: We performed a combined RNA-seq and ChIP-seq at two diurnal time-points for three different age groups to examine the connection between age-related changes to circadian transcription and heterochromatin in neuronal tissue. Our analysis focused on uncovering the relationships between long non-coding RNA (lncRNA) and age-related changes to histone H3 lysine 9 tri-methylation (H3K9me3), in part because the Period (Per) complex can direct facultative heterochromatin and models of aging suggest age-related changes to heterochromatin and DNA methylation. Our results reveal that lncRNAs and circadian output change dramatically with age, but the core clock genes remain rhythmic. Age-related changes in clock-controlled gene (ccg) expression indicate there are age-dependent circadian output that change from anabolic to catabolic processes during aging. In addition, there are diurnal and age-related changes in H3K9me3 that coincide with changes in transcription.

CONCLUSIONS: The data suggest a model where some age-related changes in diurnal expression are partially attributed to age-related alterations to rhythmic facultative heterochromatin. The changes in heterochromatin are potentially mediated by changes in diurnal lncRNA creating an interlocked circadian-chromatin regulatory network that undergoes age-dependent metamorphosis.}, } @article {pmid30373514, year = {2018}, author = {Liu, S and Xu, C and Zhang, Y and Liu, J and Yu, B and Liu, X and Dehmer, M}, title = {Feature selection of gene expression data for Cancer classification using double RBF-kernels.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {396}, pmid = {30373514}, issn = {1471-2105}, support = {ZR2015AM017//Natural Science Foundation of Shandong Province/ ; P26142//Austrian Science Funds/ ; Nos. 61877064//National Natural Science Foundation of China/ ; }, mesh = {*Algorithms ; Computational Biology/*methods ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Proteins/*genetics ; Neoplasms/*classification/*genetics ; Phenotype ; }, abstract = {BACKGROUND: Using knowledge-based interpretation to analyze omics data can not only obtain essential information regarding various biological processes, but also reflect the current physiological status of cells and tissue. The major challenge to analyze gene expression data, with a large number of genes and small samples, is to extract disease-related information from a massive amount of redundant data and noise. Gene selection, eliminating redundant and irrelevant genes, has been a key step to address this problem.

RESULTS: The modified method was tested on four benchmark datasets with either two-class phenotypes or multiclass phenotypes, outperforming previous methods, with relatively higher accuracy, true positive rate, false positive rate and reduced runtime.

CONCLUSIONS: This paper proposes an effective feature selection method, combining double RBF-kernels with weighted analysis, to extract feature genes from gene expression data, by exploring its nonlinear mapping ability.}, } @article {pmid30373513, year = {2018}, author = {Zhang, J and Hu, J and Shen, H and Zhang, Y and Sun, D and Pu, X and Yang, Q and Fan, Q and Lin, B}, title = {Genomic analysis of the Phalaenopsis pathogen Dickeya sp. PA1, representing the emerging species Dickeya fangzhongdai.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {782}, pmid = {30373513}, issn = {1471-2164}, support = {2015A030312002//Natural Science Foundation of Guangdong Province/ ; 31300118//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Dickeya sp. strain PA1 is the causal agent of bacterial soft rot in Phalaenopsis, an important indoor orchid in China. PA1 and a few other strains were grouped into a novel species, Dickeya fangzhongdai, and only the orchid-associated strains have been shown to cause soft rot symptoms.

METHODS: We constructed the complete PA1 genome sequence and used comparative genomics to explore the differences in genomic features between D. fangzhongdai and other Dickeya species.

RESULTS: PA1 has a 4,979,223-bp circular genome with 4269 predicted protein-coding genes. D. fangzhongdai was phylogenetically similar to Dickeya solani and Dickeya dadantii. The type I to type VI secretion systems (T1SS-T6SS), except for the stt-type T2SS, were identified in D. fangzhongdai. The three phylogenetically similar species varied significantly in terms of their T5SSs and T6SSs, as did the different D. fangzhongdai strains. Genomic island (GI) prediction and synteny analysis (compared to D. fangzhongdai strains) of PA1 also indicated the presence of T5SSs and T6SSs in strain-specific regions. Two typical CRISPR arrays were identified in D. fangzhongdai and in most other Dickeya species, except for D. solani. CRISPR-1 was present in all of these Dickeya species, while the presence of CRISPR-2 varied due to species differentiation. A large polyketide/nonribosomal peptide (PK/NRP) cluster, similar to the zeamine biosynthetic gene cluster in Dickeya zeae rice strains, was discovered in D. fangzhongdai and D. solani. The D. fangzhongdai and D. solani strains might recently have acquired this gene cluster by horizontal gene transfer (HGT).

CONCLUSIONS: Orchid-associated strains are the typical members of D. fangzhongdai. Genomic analysis of PA1 suggested that this strain presents the genomic characteristics of this novel species. Considering the absence of the stt-type T2SS, the presence of CRISPR loci and the zeamine biosynthetic gene cluster, D. fangzhongdai is likely a transitional form between D. dadantii and D. solani. This is supported by the later acquisition of the zeamine cluster and the loss of CRISPR arrays by D. solani. Comparisons of phylogenetic positions and virulence determinants could be helpful for the effective quarantine and control of this emerging species.}, } @article {pmid30373512, year = {2018}, author = {Wojciechowska, N and Marzec-Schmidt, K and Kalemba, EM and Zarzyńska-Nowak, A and Jagodziński, AM and Bagniewska-Zadworna, A}, title = {Autophagy counteracts instantaneous cell death during seasonal senescence of the fine roots and leaves in Populus trichocarpa.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {260}, pmid = {30373512}, issn = {1471-2229}, support = {2012/07/E/NZ9/00194//National Science Center, Poland/ ; 2016/23/N/NZ3/00073//National Science Center, Poland/ ; }, mesh = {Autophagy/*physiology ; Cell Survival ; Gene Expression Regulation, Plant ; Plant Cells/physiology ; Plant Leaves/*cytology/physiology ; Plant Proteins/genetics/metabolism ; Plant Roots/anatomy & histology/*cytology/physiology ; Populus/*cytology/*physiology ; Seasons ; }, abstract = {BACKGROUND: Senescence, despite its destructive character, is a process that is precisely-regulated. The control of senescence is required to achieve remobilization of resources, a principle aspect of senescence. Remobilization allows plants to recapture valuable resources that would otherwise be lost to the environment with the senescing organ. Autophagy is one of the critical processes that is switched on during senescence. This evolutionarily conserved process plays dual, antagonistic roles. On the one hand, it counteracts instantaneous cell death and allows the process of remobilization to be set in motion, while on the other hand, it participates in the degradation of cellular components. Autophagy has been demonstrated to occur in many plant species during the senescence of leaves and flower petals. Little is known, however, about the senescence process in other ephemeral organs, such as fine roots, whose lifespan is also relatively short. We hypothesized that, like the case of seasonal leaf senescence, autophagy also plays a role in the senescence of fine roots, and that both processes are synchronized in their timing.

RESULTS: We evaluated which morphological and cytological symptoms are universal or unique in the senescence of fine roots and leaves. The results of our study confirmed that autophagy plays a key role in the senescence of fine roots, and is associated also with the process of cellular components degradation. In both organs, structures related to autophagy were observed, such as autophagic bodies and autophagosomes. The role of autophagy in the senescence of these plant organs was further confirmed by an analysis of ATG gene expression and protein detection.

CONCLUSIONS: The present study is the first one to examine molecular mechanisms associated with the senescence of fine roots, and provide evidence that can be used to determine whether senescence of fine roots can be treated as another example of developmentally programmed cell death (dPCD). Our results indicate that there is a strong similarity between the senescence of fine roots and other ephemeral organs, suggesting that this process occurs by the same autophagy-related mechanisms in all plant ephemeral organs.}, } @article {pmid30373510, year = {2018}, author = {Maróti, Z and Boldogkői, Z and Tombácz, D and Snyder, M and Kalmár, T}, title = {Evaluation of whole exome sequencing as an alternative to BeadChip and whole genome sequencing in human population genetic analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {778}, pmid = {30373510}, issn = {1471-2164}, abstract = {BACKGROUND: Understanding the underlying genetic structure of human populations is of fundamental interest to both biological and social sciences. Advances in high-throughput genotyping technology have markedly improved our understanding of global patterns of human genetic variation. The most widely used methods for collecting variant information at the DNA-level include whole genome sequencing, which remains costly, and the more economical solution of array-based techniques, as these are capable of simultaneously genotyping a pre-selected set of variable DNA sites in the human genome. The largest publicly accessible set of human genomic sequence data available today originates from exome sequencing that comprises around 1.2% of the whole genome (approximately 30 million base pairs).

RESULTS: To unbiasedly compare the effect of SNP selection strategies in population genetic analysis we subsampled the variants of the same highly curated 1 K Genome dataset to mimic genome, exome sequencing and array data in order to eliminate the effect of different chemistry and error profiles of these different approaches. Next we compared the application of the exome dataset to the array-based dataset and to the gold standard whole genome dataset using the same population genetic analysis methods.

CONCLUSIONS: Our results draw attention to some of the inherent problems that arise from using pre-selected SNP sets for population genetic analysis. Additionally, we demonstrate that exome sequencing provides a better alternative to the array-based methods for population genetic analysis. In this study, we propose a strategy for unbiased variant collection from exome data and offer a bioinformatics protocol for proper data processing.}, } @article {pmid30373509, year = {2018}, author = {Sarfraz, Z and Iqbal, MS and Pan, Z and Jia, Y and He, S and Wang, Q and Qin, H and Liu, J and Liu, H and Yang, J and Ma, Z and Xu, D and Yang, J and Zhang, J and Gong, W and Geng, X and Li, Z and Cai, Z and Zhang, X and Zhang, X and Huang, A and Yi, X and Zhou, G and Li, L and Zhu, H and Qu, Y and Pang, B and Wang, L and Iqbal, MS and Jamshed, M and Sun, J and Du, X}, title = {Integration of conventional and advanced molecular tools to track footprints of heterosis in cotton.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {776}, pmid = {30373509}, issn = {1471-2164}, support = {31571716//National Natural Science Foundation of China/ ; 2016YFD0101401//The National Key Research and Development Program of China/ ; 2016YFD0100203//The National Key Research and Development Program of China/ ; 2013BAD01B03//The National Science and Technology Support Program of China/ ; }, abstract = {BACKGROUND: Heterosis, a multigenic complex trait extrapolated as sum total of many phenotypic features, is widely utilized phenomenon in agricultural crops for about a century. It is mainly focused on establishing vigorous cultivars with the fact that its deployment in crops necessitates the perspective of genomic impressions on prior selection for metric traits. In spite of extensive investigations, the actual mysterious genetic basis of heterosis is yet to unravel. Contemporary crop breeding is aimed at enhanced crop production overcoming former achievements. Leading cotton improvement programs remained handicapped to attain significant accomplishments.

RESULTS: In mentioned context, a comprehensive project was designed involving a large collection of cotton accessions including 284 lines, 5 testers along with their respective F1 hybrids derived from Line × Tester mating design were evaluated under 10 diverse environments. Heterosis, GCA and SCA were estimated from morphological and fiber quality traits by L × T analysis. For the exploration of elite marker alleles related to heterosis and to provide the material carrying such multiple alleles the mentioned three dependent variables along with trait phenotype values were executed for association study aided by microsatellites in mixed linear model based on population structure and linkage disequilibrium analysis. Highly significant 46 microsatellites were discovered in association with the fiber and yield related traits under study. It was observed that two-thirds of the highly significant associated microsatellites related to fiber quality were distributed on D sub-genome, including some with pleiotropic effect. Newly discovered 32 hQTLs related to fiber quality traits are one of prominent findings from current study. A set of 96 exclusively favorable alleles were discovered and C tester (A971Bt) posited a major contributor of these alleles primarily associated with fiber quality.

CONCLUSIONS: Hence, to uncover hidden facts lying within heterosis phenomenon, discovery of additional hQTLs is required to improve fibre quality. To grab prominent improvement in influenced fiber quality and yield traits, we suggest the A971 Bt cotton cultivar as fundamental element in advance breeding programs as a parent of choice.}, } @article {pmid30372699, year = {2018}, author = {Yabiku, RS and Guaragna, MS and de Sousa, LM and Fabbri-Scallet, H and Mazzola, TN and Piveta, CSC and de Souza, ML and Guerra-Júnior, G and de Mello, MP and Maciel-Guerra, AT}, title = {A Search for Disorders of Sex Development among Infertile Men.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000493877}, pmid = {30372699}, issn = {1661-5433}, abstract = {A retrospective cross-sectional study was performed in a DSD clinic at a tertiary service (University Hospital) to estimate the frequency of disorders of sex development (DSD) among men who seek medical care because of infertility. The sample included 84 men >20 years of age referred from 2010-2017 due to oligozoospermia or nonobstructive azoospermia of unknown etiology. Twelve cases (14%) were diagnosed as DSD, including Klinefelter Syndrome, 46,XX testicular DSD, and mild androgen insensitivity syndrome. Y chromosome microdeletions were detected in 2 patients. Among the remaining 70 cases there were patients with chromosome abnormalities which are not included in the DSD classification as well as rare NR5A1 variants of uncertain significance and hypergonadotropic hypogonadism and microorchidism in 46,XY subjects. In conclusion, the frequency of DSD in this study was 14%, consisting mainly of sex chromosome abnormalities but also 46,XX and 46,XY DSD. However, this figure may increase as further investigations are conducted in idiopathic cases with signs of primary testicular failure, which may present partial gonadal dysgenesis.}, } @article {pmid30372409, year = {2018}, author = {Xue, M and Wen, CQ and Liu, L and Fang, BZ and Salam, N and Huang, XM and Liu, YF and Xiao, M and Li, WJ}, title = {Halomonas litopenaei sp. nov., a moderately halophilic, exopolysaccharide-producing bacterium isolated from a shrimp hatchery.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3914-3921}, doi = {10.1099/ijsem.0.003090}, pmid = {30372409}, issn = {1466-5034}, mesh = {Animals ; *Aquaculture ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Decapoda (Crustacea) ; Fatty Acids/chemistry ; Halomonas/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {Two Gram-stain negative, moderately halophilic, exopolysaccharide-producing bacteria, designated strains SYSU ZJ2214T and SYSU XM8, were isolated from rearing water and larvae from shrimp hatcheries, respectively. Cells of the strains were aerobic, motile and short-rod-shaped. They grew at NaCl concentrations of 0.5-22 % (w/v), at 4-45 °C and at pH 6-9. Pairwise comparison of 16S rRNA gene sequences revealed that strains SYSU ZJ2214T and SYSU XM8 were most closely related to Halomonas denitrificans M29T (98.3 and 98.2 % similarity, respectively). Strains SYSU ZJ2214T and SYSU XM8 shared an average nucleotide identity of 99.9 % between them. The DNA G+C contents were calculated at 64.1 % for both strains from the draft genome information. The major cellular fatty acids (>5 %) were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C12 : 0 3-OH, and the predominant respiratory quinone was ubiquinone Q-9. Their main polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, four unidentified phospholipids and three unidentified lipids. On the basis of phenotypic, genotypic and phylogenetic data, strains SYSU ZJ2214T and SYSU XM8 merit recognition as representatives of a novel species of the genus Halomonas, for which the name Halomonas litopenaei sp. nov. is proposed. The type strain is SYSU ZJ2214T (=NBRC 111829T=KCTC 42974T).}, } @article {pmid30372407, year = {2018}, author = {Jeong, JJ and Sang, MK and Lee, DW and Choi, IG and Kim, KD}, title = {Chryseobacterium phosphatilyticum sp. nov., a phosphate-solubilizing endophyte isolated from cucumber (Cucumis sativus L.) root.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003091}, pmid = {30372407}, issn = {1466-5034}, abstract = {A bacterial strain, designated as ISE14T, with Gram-stain-negative and non-motile rod-shaped cells, was isolated from the root of a cucumber plant collected in a field in Iksan, Republic of Korea and was characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ISE14T represented a member of the genus Chryseobacterium and was closely related to Chryseobacterium viscerum 687B-08T (16S rRNA gene sequence similarity of 98.50 %), Chryseobacterium lactis NCTC 11390T (98.49 %), Chryseobacterium ureilyticum F-Fue-04IIIaaaaT (98.49 %) and Chryseobacterium oncorhynchi 701B-08T (98.04 %). Average nucleotide identity values between genome sequences of strain ISE14T and the closely related species ranged from 81.44 to 83.15 %, which were lower than the threshold of 95 % (corresponding to a DNA-DNA hybridization value of 70 %). The DNA G+C content of strain ISE14T was 36.3 mol%. The dominant fatty acids were iso-C15 : 0, summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl), summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c) and iso-C17 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, three unidentified aminolipids and eight unidentified lipids; the predominant respiratory quinone was MK-6. On the basis of the evidence presented in this study, strain ISE14T can be distinguished from closely related species belonging to the genus Chryseobacterium. Thus, strain ISE14T is a novel species of the genus Chryseobacterium, for which the name Chryseobacteriumphosphatilyticum sp. nov. is proposed. The type strain is ISE14T (=KACC 19820T=JCM 32876T).}, } @article {pmid30371775, year = {2018}, author = {Stam, R and Münsterkötter, M and Pophaly, SD and Fokkens, L and Sghyer, H and Güldener, U and Hückelhoven, R and Hess, M}, title = {A New Reference Genome Shows the One-Speed Genome Structure of the Barley Pathogen Ramularia collo-cygni.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3243-3249}, doi = {10.1093/gbe/evy240}, pmid = {30371775}, issn = {1759-6653}, abstract = {Ramularia leaf spot has recently emerged as a major threat to barley production world-wide, causing 25% yield loss in many barley growing regions. Here, we provide a new reference genome of the causal agent, the Dothideomycete Ramularia collo-cygni. The assembly of 32 Mb consists of 78 scaffolds. We used RNA-seq to identify 11,622 genes of which 1,303 and 282 are coding for predicted secreted proteins and putative effectors respectively.The pathogen separated from its nearest sequenced relative, Zymoseptoria tritici ∼27 Ma. We calculated the divergence of the two species on protein level and see remarkably high synonymous and nonsynonymous divergence. Unlike in many other plant pathogens, the comparisons of transposable elements and gene distributions, show a very homogeneous genome for R. collo-cygni. We see no evidence for higher selective pressure on putative effectors or other secreted proteins and repetitive sequences are spread evenly across the scaffolds. These findings could be associated to the predominantly endophytic life-style of the pathogen. We hypothesize that R. collo-cygni only recently became pathogenic and that therefore its genome does not yet show the typical pathogen characteristics. Because of its high scaffold length and improved CDS annotations, our new reference sequence provides a valuable resource for the community for future comparative genomics and population genetics studies.}, } @article {pmid30371772, year = {2018}, author = {Kono, N and Tomita, M and Arakawa, K}, title = {Accelerated Laboratory Evolution Reveals the Influence of Replication on the GC Skew in Escherichia coli.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3110-3117}, pmid = {30371772}, issn = {1759-6653}, abstract = {Most bacterial genomes display contrasting strand asymmetry in a variety of features, such as nucleotide composition and gene orientation, of the two replichores separated by the replication origin and terminus. The cause for the polarization is often attributed to mutations arising from the asymmetric replication machinery. Notably, a base compositional bias known as a GC skew is focused on as a footprint of the bacterial genome evolution driven by DNA replication. Previously, although a replication driven mutation pattern responsible for the GC skew formation or the related mathematical models have been well reported, an exact impact of the replication-related elements on the genomic structure is yet actively debated, and not confirmed experimentally. However, the GC skew formation is very time consuming and challenging in the laboratory. We, therefore, used cytosine deaminase as a DNA mutator, and by monitoring the mutations during an accelerated laboratory evolution procedure with Illumina sequencing, we enabled the trial and error of the GC skew formation in high resolution. Using this technology, we succeeded in reconfirming the influence of bacterial replication machinery on the genomic structure at high resolution.}, } @article {pmid30371768, year = {2018}, author = {Cho, H and Tripathi, BM and Moroenyane, I and Takahashi, K and Kerfahi, D and Dong, K and Adams, JM}, title = {Soil pH rather than elevation determines bacterial phylogenetic community assembly on Mt. Norikura, Japan.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy216}, pmid = {30371768}, issn = {1574-6941}, abstract = {There is considerable interest in the factors which may explain variation in microbial community assembly processes. In this study, we investigated bacterial community assembly, phylogenetic diversity and the relative role of deterministic and stochastic processes along environmental gradients on Mt. Norikura, Japan. DNA extracted from soil samples collected at a range of elevations was PCR amplified for bacterial 16S rRNA gene targeting the V3-V4 region, and sequenced using Illumina MiSeq. We hypothesized that elevation would be a strong predictor of phylogenetic community assembly, with communities being more phylogenetically clustered towards higher elevations, due to more extreme physiological conditions. We also hypothesized a greater role of stochasticity at the highest elevations, due to more frequent soil disturbance. Contrary to our hypotheses, we found that the strength of phylogenetic clustering and the role of stochasticity were strongly related to soil pH, with phylogenetic clustering and deterministic processes being strongest at lower soil pH values. Moreover, there was no trend towards stronger influence of phylogenetic clustering and stochasticity in the upper elevations of Mt. Norikura. These results reveal an overwhelming influence of soil pH on phylogenetic community assembly of soil bacteria, even when a range of other environmental gradients are present.}, } @article {pmid30370693, year = {2018}, author = {Baab, KL}, title = {Evolvability and craniofacial diversification in genus Homo.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2781-2791}, doi = {10.1111/evo.13637}, pmid = {30370693}, issn = {1558-5646}, support = {//Sigma Xi Foundation/ ; BCS 04-24262//National Science Foundation/ ; DBI 96-02234//National Science Foundation/ ; DGE 03-33425//National Science Foundation/ ; //L.S.B. Leakey Foundation/ ; }, abstract = {There is abundant theoretical and empirical evidence for the influence of variational properties of populations on microevolution, and more limited support for their lasting impact during macroevolution. This study applies evolutionary quantitative genetic approaches to assess the long-term impact of within-population phenotypic variation and covariation (the P matrix) on population divergence in recent humans and species diversification in genus Homo. Similarity between the primary axes of within- and between-population craniofacial variation confirms a role for pmax in human population divergence, although diversification is not constrained to be unidimensional. The long term impact of the P matrix on craniofacial evolution is supported by higher-than-average evolvabilities along most branches of the Homo tree, but statistical uncertainty inherent in the data reduce confidence in this conclusion. Higher evolvability is not statistically correlated with increased rate of evolution, although the relationship is in the predicted direction. This is due in part to the high evolutionary rate on the early modern human branch despite its moderate level of evolvability. There was evidence for neutral evolution as well as directional and stabilizing selection during evolution of our genus during the Plio-Pleistocene using generalized genetic distance as a test statistic.}, } @article {pmid30370653, year = {2018}, author = {Maestri, R}, title = {Digest: Adaptive radiations and the multidimensional niche.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2828-2829}, doi = {10.1111/evo.13635}, pmid = {30370653}, issn = {1558-5646}, abstract = {Adaptive radiations depend critically on ecological opportunity as a driver. Aristide et al. (2018) found that a model incorporating the multivariate niche explains the morphological divergence in New World monkeys better than models with a single ecological axis. This raises the question of whether other continental radiations would show signals of adaptive radiation if the niche is more accurately described.}, } @article {pmid30370648, year = {2018}, author = {DeCasien, AR and Thompson, NA and Williams, SA and Shattuck, MR}, title = {Encephalization and longevity evolved in a correlated fashion in Euarchontoglires but not in other mammals.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2617-2631}, doi = {10.1111/evo.13633}, pmid = {30370648}, issn = {1558-5646}, support = {DGE1342536//National Science Foundation/ ; }, abstract = {Across mammals, encephalization and longevity show a strong correlation. It is not clear, however, whether these traits evolved in a correlated fashion within mammalian orders, or when they do, whether one trait drives changes in the other. Here, we compared independent and correlated evolutionary models to identify instances of correlated evolution within six mammalian orders. In cases of correlated evolution, we subsequently examined transition patterns between small/large relative brain size and short/long lifespan. In four mammalian orders, these traits evolved independently. This may reflect constraints related to energy allocation, predation avoidance tactics, and reproductive strategies. Within both primates and rodents, and their parent clade Euarchontoglires, we found evidence for correlated evolution. In primates, transition patterns suggest relatively larger brains likely facilitated the evolution of long lifespans. Because larger brains prolong development and reduce fertility rates, they may be compensated for with longer lifespans. Furthermore, encephalization may enable cognitively-complex strategies that reduce extrinsic mortality. Rodents show an inverse pattern of correlated evolution, whereby long lifespans appear to have facilitated the evolution of relatively larger brains. This may be because longer lived organisms have more to gain from investment in encephalization. Together, our results provide evidence for the correlated evolution of encephalization and longevity, but only in some mammalian orders.}, } @article {pmid30370620, year = {2019}, author = {Li, Y and Chen, Z and He, JZ and Wang, Q and Shen, C and Ge, Y}, title = {Ectomycorrhizal fungi inoculation alleviates simulated acid rain effects on soil ammonia oxidizers and denitrifiers in Masson pine forest.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {299-313}, doi = {10.1111/1462-2920.14457}, pmid = {30370620}, issn = {1462-2920}, support = {41671254//National Natural Science Foundation of China/ ; CAFRIFEEP201402//National Natural Science Foundation of China/ ; CAFRIFEEP201402//the Public Welfare Project of the National Scientific Research Institution/ ; XDB15020200//Chinese Academy of Sciences/ ; }, abstract = {Acid rain can cause severe effects on soil biota and nutrient biogeochemical cycles in the forest ecosystem, but how plant-symbiotic ectomycorrhizal fungi will modulate the effects remains unknown. Here, we conducted a full factorial field experiment in a Masson pine forest by simultaneously controlling the acidity of the simulated rain (pH 5.6 vs. pH 3.5) and the ectomycorrhizal fungi Pisolithus tinctorius inoculation (non-inoculation vs. inoculation), to investigate the effects on ammonia oxidizers and denitrifiers. After 10 months, compared with the control (rain pH 5.6, and non-inoculation), simulated acid rain (pH 3.5) reduced soil nutrient content, decreased archaeal amoA gene abundance and inhibited denitrification enzyme activity. Also, simulated acid rain altered the community compositions of all the examined functional genes (archaeal amoA, bacterial amoA, nirK, nirS and nosZ). However, inoculation with ectomycorrhizal fungi under acid rain stress recovered soil nutrient content, archaeal amoA gene abundance and denitrification enzyme activity to levels comparable to the control, suggesting that ectomycorrhizal fungi inoculation ameliorates simulated acid rain effects. Taken together, ectomycorrhizal fungi inoculation - potentially through improving soil substrate availability - could alleviate the deleterious effects of acid rain on nitrogen cycling microbes in forest soils.}, } @article {pmid30370610, year = {2018}, author = {López-Pérez, M and Haro-Moreno, JM and de la Torre, JR and Rodriguez-Valera, F}, title = {Novel Caudovirales associated with Marine Group I Thaumarchaeota assembled from metagenomes.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14462}, pmid = {30370610}, issn = {1462-2920}, support = {APOSTD/2016/051//Valencian Consellería de Educació, Investigació, Cultura i Esport/ ; BES-2014-067828//Spanish Ministerio de Economía y Competitividad/ ; PROMETEO II/2014/012//Generalitat Valenciana/ ; CGL2015-71523-REDC//Spanish Ministerio de Economía, Industria y Competitividad/ ; VIREVO' CGL2016-76273-P [AEI/FEDER, EU]//FEDER funds/ ; MEDIMAX' BFPU2013-48007-P//FEDER funds/ ; }, abstract = {Marine Group I (MGI) Thaumarchaeota are some of the most abundant microorganisms in the deep ocean and responsible for much of the ammonia oxidation occurring in this environment. In this work, we present 35 sequences assembled from metagenomic samples of the first uncultivated Caudovirales viruses associated with Thaumarchaeota, which we designated marthavirus. Most of the sequences were obtained from cellular metagenomes confirming that they represent an important tool to study environmental viral communities due to cells retrieved while undergoing viral lysis. Metagenomic recruitment showed that this viral population is formed by very divergent entities with high intrapopulation homogeneity. However, metatranscriptomic analyses revealed the same differential expression profile with the capsid as major transcript, indicative of viruses during the lytic cycle. The cobalamine biosynthesis gene cobS, an auxiliary metabolic gene, was also highly expressed during the infection. These analyses expand our understanding of the global diversity of archaeal viruses.}, } @article {pmid30370586, year = {2018}, author = {Chen, Y and Li, B and Xu, X and Zhang, Z and Tian, S}, title = {The pH-responsive PacC transcription factor plays pivotal roles in virulence and patulin biosynthesis in Penicillium expansum.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4063-4078}, doi = {10.1111/1462-2920.14453}, pmid = {30370586}, issn = {1462-2920}, support = {2016YFD0400902//National Key R&D Program of China/ ; 31530057//National Natural Science Foundation of China/ ; 31722043//National Natural Science Foundation of China/ ; }, abstract = {The PacC (loss or reduction in phosphatase activity at acid but not at alkaline pH [Pac]) transcription factor regulates environmental adaptation, secondary metabolism and virulence in many fungal pathogens. Here, we report the functions of PacC in Penicillium expansum, a postharvest pathogenic fungus in horticultural crops, and ascertain that the gene expression and proteolytic processing of PePacC are strictly pH-dependent. Loss of PePacC resulted in an obvious decrease in growth and conidiation of P. expansum cultured in both acidic and alkaline conditions. The ΔPePacC mutant lost the ability of patulin production at pH values above 6.0 because expressions of all the genes in patulin cluster were significantly down-regulated. Additionally, virulence of the ΔPePacC mutant was obviously reduced in pear and apple fruits. Proteome analysis revealed that PePacC could function as an activator or repressor for different target proteins, including calreticulin (PeCRT) and sulfate adenylyltransferase (PeSAT), which were further proved to be involved in virulence of P. expansum. Our results demonstrate important roles for PePacC in patulin biosynthesis via limiting expressions of the genes in the cluster, and in pathogenesis via mediating a known virulence factor glucose oxidase (PeGOD) and new virulence factors, such as PeCRT and PeSAT.}, } @article {pmid30370577, year = {2018}, author = {Sun, J and Mausz, MA and Chen, Y and Giovannoni, SJ}, title = {Microbial trimethylamine metabolism in marine environments.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14461}, pmid = {30370577}, issn = {1462-2920}, abstract = {Trimethylamine (TMA) is common in marine environments. Although the presence of this compound in the oceans has been known for a long time, unlike the mammalian gastrointestinal tract, where TMA metabolism by microorganisms has been studied intensely, many questions remain unanswered about the microbial metabolism of marine TMA. This minireview summarizes what is currently known about the sources and fate of TMA in marine environments and the different pathways and enzymes involved in TMA metabolism in marine bacteria. This review also raises several questions about microbial TMA metabolism in the marine environments and proposes potential directions for future studies.}, } @article {pmid30370539, year = {2018}, author = {Pearse, WD and Morales-Castilla, I and James, LS and Farrell, M and Boivin, F and Davies, TJ}, title = {Complexity is complicated and so too is comparing complexity metrics-A response to Mikula et al. (2018).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2836-2838}, doi = {10.1111/evo.13636}, pmid = {30370539}, issn = {1558-5646}, support = {ABI-1759965//Division of Biological Infrastructure/ ; 168004//Fonds de Recherche du Québec - Nature et Technologies/ ; 18-CS-11046000-041//U.S. Forest Service/ ; //Natural Sciences and Engineering Research Council of Canada/ ; EF-1802605//Division of Emerging Frontiers/ ; }, abstract = {In a recent publication (Pearse et al. 2018b), we explored the macroevolution and macroecology of passerine song using a large citizen science database of bird songs and powerful machine learning tools. Mikula et al. (2018) examine a small subset (<8%) of the data we used, and suggest that our metric of song complexity, the SD of frequency (SDF), does not correlate to other metrics of birdsong complexity, specifically syllable repertoire size and syllable diversity. We comment on the diversity of complexity metrics that exist in the field at present, and, while acknowledging that metrics may differ, outline how this variety allows us to ask more biologically nuanced questions. We see no reason or need for all complexity metrics to be correlated. Since different complexity metrics have been, and will continue to be, used, we outline how metrics could be fairly compared in the future.}, } @article {pmid30370448, year = {2018}, author = {Vicens, A and Treviño, CL}, title = {Positive Selection in the Evolution of Mammalian CRISPs.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {635-645}, pmid = {30370448}, issn = {1432-1432}, support = {IN203116//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; IJCI-2016-29550//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; }, abstract = {Cysteine-RIch Secretory Proteins (CRISPs) constitute a versatile family, with functions in reptilian venom and mammalian reproduction. Mammals generally express three CRISPs, four in mice, and all are highly expressed in male reproductive tissues, either testis or accessory organs. Because reproductive proteins often evolve adaptively in response to post-copulatory sexual selection, we hypothesized that mammalian CRISPs, with important roles in male reproduction, could have undergone positive selection promoting their divergence. We explored the molecular adaptation of mammalian CRISPs applying phylogenetic methods. Our analyses revealed the evidence of positive selection in all mammalian CRISPs. The intensity of positive selection was heterogeneous among CRISP members, being stronger in CRISP3 than in CRISP1 and CRISP2, and also across functional domains, having stronger impact on Pathogenesis-Related 1 (PR-1) in CRISP2 and on Ion Channel Regulator (ICR) in CRISP1 and CRISP3. In addition, we discovered a new CRISP in some rodent species, suggesting that the acquisition of new CRISP components could contribute to male reproductive success or to acquire new physiological roles. Signatures of positive selection were not focused on any particular mammalian group, suggesting that adaptive evolution is a recurrent pattern in mammalian CRISPs. Our findings support a model of CRISP family diversification driven by episodes of duplication and posterior neofunctionalization, and provide potential adaptive changes responsible for interspecific differences in CRISPs activity.}, } @article {pmid30369007, year = {2018}, author = {Arriaza, B and Amarasiriwardena, D and Standen, V and Yáñez, J and Van Hoesen, J and Figueroa, L}, title = {Living in poisoning environments: Invisible risks and human adaptation.}, journal = {Evolutionary anthropology}, volume = {27}, number = {5}, pages = {188-196}, doi = {10.1002/evan.21720}, pmid = {30369007}, issn = {1520-6505}, support = {1170120//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; 1625004//NSF-MRI - DBI/ ; 1625004//National Science Foundation/ ; 0959028//National Science Foundation/ ; }, mesh = {Archaeology ; Arsenic/analysis/metabolism ; *Arsenic Poisoning ; Child ; *Environmental Exposure ; Humans ; Mummies ; Polydactyly ; Skin Diseases ; South America ; }, abstract = {This article describes the hidden natural chemical contaminants present in a unique desert environment and their health consequences on ancient populations. Currently, millions of people are affected worldwide by toxic elements such as arsenic. Using data gathered from Atacama Desert mummies, we discuss long-term exposure and biocultural adaptation to toxic elements. The rivers that bring life to the Atacama Desert are paradoxically laden with arsenic and other minerals that are invisible and tasteless. High intake of these toxic elements results in severe health and behavioral problems, and even death. We demonstrate that Inca colonies, from Camarones 9 site, were significantly affected by chemical contaminants in their food and water. It appears however, some modern-day Andean populations resist the elevated levels of arsenic exposure as a result of positive selection mediated via the arsenic methyltransferase enzyme and display more tolerance to high chemical doses. This article further debate the effects of natural pollution and biocultural adaptation of past populations.}, } @article {pmid30368655, year = {2018}, author = {Bahn, PR}, title = {The Tangled Tree: a Radical New History of Life by David Quammen, Simon & Schuster, 2018.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {3}, pages = {343-344}, doi = {10.1007/s11084-018-9566-5}, pmid = {30368655}, issn = {1573-0875}, mesh = {*Book Reviews as Topic ; Evolution, Molecular ; Humans ; *Origin of Life ; Phylogeny ; }, } @article {pmid30368244, year = {2018}, author = {Fontana, A and Kougias, PG and Treu, L and Kovalovszki, A and Valle, G and Cappa, F and Morelli, L and Angelidaki, I and Campanaro, S}, title = {Microbial activity response to hydrogen injection in thermophilic anaerobic digesters revealed by genome-centric metatranscriptomics.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {194}, pmid = {30368244}, issn = {2049-2618}, support = {12-132654//Innovation Fond/ ; }, abstract = {BACKGROUND: The expansion of renewable energy produced by windmills and photovoltaic panels has generated a considerable electricity surplus, which can be utilized in water electrolysis systems for hydrogen production. The resulting hydrogen can then be funneled to anaerobic digesters for biogas upgrading (biomethanation) purposes (power-to-methane) or to produce high value-added compounds such as short-chain fatty acids (power-to-chemicals). Genome-centric metagenomics and metatranscriptomic analyses were performed to better understand the metabolic dynamics associated with H2 injection in two different configurations of anaerobic digesters treating acidic wastes, specifically cheese manufacturing byproducts. These approaches revealed the key-genes involved in methanation and carbon fixation pathways at species level.

RESULTS: The biogas upgrading process in the single-stage configuration increased the CH4 content by 7%. The dominant methanogenic species responsible for the upregulation of the hydrogenotrophic pathway in this reactor was Methanothermobacter wolfeii UC0008. In the two-stage configuration, H2 injection induced an upregulation of CO2 fixation pathways producing short-chain fatty acids, mainly acetate and butyrate. In this configuration, the abundant species Anaerobaculum hydrogeniformans UC0046 and Defluviitoga tunisiensis UC0050 primarily upregulated genes related to electron transport chains, suggesting putative syntrophisms with hydrogen scavenger microbes. Interestingly, Tepidanaerobacter acetatoxydans UC0018 did not act as an acetate-oxidizer in either reactor configurations, and instead regulated pathways involved in acetate production and uptake. A putative syntrophic association between Coprothermobacter proteolyticus UC0011 and M. wolfeii UC0008 was proposed in the two-stage reactor. In order to support the transcriptomic findings regarding the hydrogen utilization routes, an advanced bioconversion model was adapted for the simulation of the single- and two-stage reactor setups.

CONCLUSIONS: This is the first study investigating biogas reactor metatranscriptome dynamics following hydrogen injection for biomethanation and carbon fixation to short-chain fatty acids purposes. The same microbes showed different patterns of metabolic regulation in the two reactor configurations. It was observed an effect of the specialized acidogenic reactor on the overall microbial consortium composition and activity in the two-stage digester. There were also suggested the main species responsible for methanation, short-chain fatty acids production, and electron transport chain mechanisms, in both reactor configurations.}, } @article {pmid30367976, year = {2019}, author = {Cole, TL and Rawlence, NJ and Dussex, N and Ellenberg, U and Houston, DM and Mattern, T and Miskelly, CM and Morrison, KW and Scofield, RP and Tennyson, AJD and Thompson, DR and Wood, JR and Waters, JM}, title = {Ancient DNA of crested penguins: Testing for temporal genetic shifts in the world's most diverse penguin clade.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {72-79}, doi = {10.1016/j.ympev.2018.10.025}, pmid = {30367976}, issn = {1095-9513}, abstract = {Human impacts have substantially reduced avian biodiversity in many parts of the world, particularly on isolated islands of the Pacific Ocean. The New Zealand archipelago, including its five subantarctic island groups, holds breeding grounds for a third of the world's penguin species, including several representatives of the diverse crested penguin genus Eudyptes. While this species-rich genus has been little studied genetically, recent population estimates indicate that several Eudyptes taxa are experiencing demographic declines. Although crested penguins are currently limited to southern regions of the New Zealand archipelago, prehistoric fossil and archaeological deposits suggest a wider distribution during prehistoric times, with breeding ranges perhaps extending to the North Island. Here, we analyse ancient, historic and modern DNA sequences to explore two hypotheses regarding the recent history of Eudyptes in New Zealand, testing for (1) human-driven extinction of Eudyptes lineages; and (2) reduced genetic diversity in surviving lineages. From 83 prehistoric bone samples, each tentatively identified as 'Eudyptes spp.', we genetically identified six prehistoric penguin taxa from mainland New Zealand, including one previously undescribed genetic lineage. Moreover, our Bayesian coalescent analyses indicated that, while the range of Fiordland crested penguin (E. pachyrhynchus) may have contracted markedly over the last millennium, genetic DNA diversity within this lineage has remained relatively constant. This result contrasts with human-driven biodiversity reductions previously detected in several New Zealand coastal vertebrate taxa.}, } @article {pmid30367975, year = {2019}, author = {Kearns, AM and Malloy, JF and Gobbert, MK and Thierry, A and Joseph, L and Driskell, AC and Omland, KE}, title = {Nuclear introns help unravel the diversification history of the Australo-Pacific Petroica robins.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {48-54}, doi = {10.1016/j.ympev.2018.10.024}, pmid = {30367975}, issn = {1095-9513}, abstract = {Australo-Pacific Petroica robins are known for their striking variability in sexual plumage coloration. Molecular studies in recent years have revised the taxonomy of species and subspecies boundaries across the southwest Pacific and New Guinea. However, these studies have not been able to resolve phylogenetic relationships within Petroica owing to limited sampling of the nuclear genome. Here, we sequence five nuclear introns across all species for which fresh tissue was available. Nuclear loci offer support for major geographic lineages that were first inferred from mtDNA. We find almost no shared nuclear alleles between currently recognized species within the New Zealand and Australian lineages, whereas the Pacific robin radiation has many shared alleles. Multilocus coalescent species trees based on nuclear loci support a sister relationship between the Australian lineage and the Pacific robin radiation-a node that is poorly supported by mtDNA. We also find discordance in support for a sister relationship between the similarly plumaged Rose Robin (P. rosea) and Pink Robin (P. rodinogaster). Our nuclear data complement previous mtDNA studies in suggesting that the phenotypically cryptic eastern and western populations of Australia's Scarlet Robin (P. boodang) are genetically distinct lineages at the early stages of divergence and speciation.}, } @article {pmid30367846, year = {2019}, author = {Pesch, YY and Hesse, R and Ali, T and Behr, M}, title = {A cell surface protein controls endocrine ring gland morphogenesis and steroid production.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {16-28}, doi = {10.1016/j.ydbio.2018.10.007}, pmid = {30367846}, issn = {1095-564X}, abstract = {Identification of signals for systemic adaption of hormonal regulation would help to understand the crosstalk between cells and environmental cues contributing to growth, metabolic homeostasis and development. Physiological states are controlled by precise pulsatile hormonal release, including endocrine steroids in human and ecdysteroids in insects. We show in Drosophila that regulation of genes that control biosynthesis and signaling of the steroid hormone ecdysone, a central regulator of developmental progress, depends on the extracellular matrix protein Obstructor-A (Obst-A). Ecdysone is produced by the prothoracic gland (PG), where sensory neurons projecting axons from the brain integrate stimuli for endocrine control. By defining the extracellular surface, Obst-A promotes morphogenesis and axonal growth in the PG. This process requires Obst-A-matrix reorganization by Clathrin/Wurst-mediated endocytosis. Our data identifies the extracellular matrix as essential for endocrine ring gland function, which coordinates physiology, axon morphogenesis, and developmental programs. As Obst-A and Wurst homologs are found among all arthropods, we propose that this mechanism is evolutionary conserved.}, } @article {pmid30367845, year = {2019}, author = {Nakao, H and Takasu, Y}, title = {Complexities in Bombyx germ cell formation process revealed by Bm-nosO (a Bombyx homolog of nanos) knockout.}, journal = {Developmental biology}, volume = {445}, number = {1}, pages = {29-36}, doi = {10.1016/j.ydbio.2018.10.012}, pmid = {30367845}, issn = {1095-564X}, abstract = {Inheritance (sequestration of a localized determinant: germplasm) and zygotic induction are two modes of metazoan primordial germ cell (PGC) specification. vasa and nanos homologs are evolutionarily conserved germline marker genes that have been used to examine the ontogeny of germ cells in various animals. In the lepidopteran insect Bombyx mori, although the lack of vasa homolog (BmVLG) protein localization as well as microscopic observation suggested the lack of germplasm, classical embryo manipulation studies and the localization pattern of Bm-nosO (one of the four nanos genes in Bombyx) maternal mRNA in the egg raised the possibility that an inheritance mode is operating in Bombyx. Here, we generated Bm-nosO knockouts to examine whether the localized mRNA acts as a localized germ cell determinant. Contrary to our expectations, Bm-nosO knockout lines could be established. However, these lines frequently produced abnormal eggs, which failed to hatch, to various extent depending on the individuals. We also found that Bm-nosO positively regulated BmVLG expression at least during embryonic stage, directly or indirectly, indicating that these genes were on the same developmental pathway for germ cell formation in Bombyx. These results suggest that these conserved genes are concerned with stable germ cell production. On the other hand, from the aspect of BmVLG as a PGC marker, we showed that maternal Bm-nosO product(s) as well as early zygotic Bm-nosO activity were redundantly involved in PGC specification; elimination of both maternal and zygotic gene activities (as in knockout lines) resulted in the apparent lack of PGCs, indicating that an inheritance mechanism indeed operates in Bombyx. This, however, together with the fact that germ cells are produced at all in Bm-nosO knockout lines, also suggests the possibility that, in Bombyx, not only this inheritance mechanism but also an inductive mechanism acts in concert to form germ cells or that loss of early PGCs are compensated for by germline regeneration: mechanisms that could enable the evolution of preformation. Thus, Bombyx could serve as an important organism in understanding the evolution of germ cell formation mechanisms; transition between preformation and inductive modes.}, } @article {pmid30367675, year = {2018}, author = {Grier, A and McDavid, A and Wang, B and Qiu, X and Java, J and Bandyopadhyay, S and Yang, H and Holden-Wiltse, J and Kessler, HA and Gill, AL and Huyck, H and Falsey, AR and Topham, DJ and Scheible, KM and Caserta, MT and Pryhuber, GS and Gill, SR}, title = {Neonatal gut and respiratory microbiota: coordinated development through time and space.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {193}, pmid = {30367675}, issn = {2049-2618}, support = {HHSN272201200005C/AI/NIAID NIH HHS/United States ; K08 AI108870/AI/NIAID NIH HHS/United States ; HHSN272201200005C//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: Postnatal development of early life microbiota influences immunity, metabolism, neurodevelopment, and infant health. Microbiome development occurs at multiple body sites, with distinct community compositions and functions. Associations between microbiota at multiple sites represent an unexplored influence on the infant microbiome. Here, we examined co-occurrence patterns of gut and respiratory microbiota in pre- and full-term infants over the first year of life, a period critical to neonatal development.

RESULTS: Gut and respiratory microbiota collected as longitudinal rectal, throat, and nasal samples from 38 pre-term and 44 full-term infants were first clustered into community state types (CSTs) on the basis of their compositional profiles. Multiple methods were used to relate the occurrence of CSTs to temporal microbiota development and measures of infant maturity, including gestational age (GA) at birth, week of life (WOL), and post-menstrual age (PMA). Manifestation of CSTs followed one of three patterns with respect to infant maturity: (1) chronological, with CST occurrence frequency solely a function of post-natal age (WOL), (2) idiosyncratic to maturity at birth, with the interval of CST occurrence dependent on infant post-natal age but the frequency of occurrence dependent on GA at birth, and (3) convergent, in which CSTs appear first in infants of greater maturity at birth, with occurrence frequency in pre-terms converging after a post-natal interval proportional to pre-maturity. The composition of CSTs was highly dissimilar between different body sites, but the CST of any one body site was highly predictive of the CSTs at other body sites. There were significant associations between the abundance of individual taxa at each body site and the CSTs of the other body sites, which persisted after stringent control for the non-linear effects of infant maturity. Canonical correlations exist between the microbiota composition at each pair of body sites, with the strongest correlations between proximal locations.

CONCLUSION: These findings suggest that early microbiota is shaped by neonatal innate and adaptive developmental responses. Temporal progression of CST occurrence is influenced by infant maturity at birth and post-natal age. Significant associations of microbiota across body sites reveal distal connections and coordinated development of the infant microbial ecosystem.}, } @article {pmid30367674, year = {2018}, author = {Murphy, AL and Gardner, DM}, title = {A simulated patient evaluation of pharmacist's performance in a men's mental health program.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {765}, pmid = {30367674}, issn = {1756-0500}, mesh = {Adult ; Community Pharmacy Services ; *Health Knowledge, Attitudes, Practice ; Health Promotion ; Humans ; Mental Disorders/*therapy ; *Patient Satisfaction ; *Patient Simulation ; Pharmacists/*standards ; *Professional-Patient Relations ; Program Evaluation ; Sleep Initiation and Maintenance Disorders/*drug therapy ; }, abstract = {OBJECTIVE: The Headstrong program, a pharmacy based men's mental health promotion program, was designed to enhance pharmacists' care of men with mental illness and addictions and was focused on six conditions. A simulated patient (SP) encounter on insomnia was used to evaluate pharmacist's performance as a part of the Headstrong program.

RESULTS: Six Headstrong pharmacists consented to participate in the SP encounter as part of the evaluation of the Headstrong program. Pharmacists' mean scores in most categories that were evaluated (e.g., pre-supply/assessment score, sleep score) were lower than expected. In assessing the SP during the encounter, pharmacists' mean score was 5.7 (SD 2.0) of a possible 13 points. No pharmacists asked about the SP's age, availability of other supports, allergies, and whether they had an existing relationship with a pharmacist. One pharmacist inquired about medical conditions, and two asked about pre-existing mental health conditions. Three pharmacists inquired about concurrent medications. The Headstrong program was discussed by half of the pharmacists and a resource recommended by the Headstrong program was suggested by one pharmacist. Several pharmacists used self-disclosure as a mechanism to support rapport building. Overall, the SP felt cared for and respected by the pharmacists and had confidence in their knowledge.}, } @article {pmid30367631, year = {2018}, author = {Liu, Q and Li, X and Yan, S and Yu, T and Yang, J and Dong, J and Zhang, S and Zhao, J and Yang, T and Mao, X and Zhu, X and Liu, B}, title = {OsWRKY67 positively regulates blast and bacteria blight resistance by direct activation of PR genes in rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {257}, pmid = {30367631}, issn = {1471-2229}, support = {31461143019//NSFC-IRRI project/ ; 2015B020231002//Science and Technology Project of Guangdong Province/ ; 2016A050502030//Science and Technology Project of Guangdong Province/ ; 2014B070706013//Science and Technology Project of Guangdong Province/ ; 2014A030310489//the Natural Science Foundation of Guangdong Province/ ; 2017LM2148//the Common Technical Innovation Team of Guangdong Province on Agricultural Seed Industry/ ; }, mesh = {Cell Nucleus/genetics ; Disease Resistance/genetics ; Gene Expression Regulation, Plant ; Gene Silencing ; Magnaporthe/pathogenicity ; Oryza/*genetics/metabolism/*microbiology ; Plant Diseases/genetics/*microbiology ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; Salicylic Acid/metabolism ; Xanthomonas/pathogenicity ; }, abstract = {BACKGROUND: WRKY proteins are one of the largest gene families and are well-known for their regulatory roles in many aspects of plant development, including plant response to both biotic and abiotic stresses. Although the roles of WRKY proteins in leaf blast resistance have been well-documented in rice, their functions in panicle blast, the most destructive type of blast disease, are still largely unknown.

RESULTS: Here, we identified that the transcription of OsWRKY67 was strongly activated by leaf and panicle blast infection. OsWRKY67 is ubiquitously expressed and sub-localized in the nucleus. Rice plants overexpressing OsWRKY67 showed quantitatively enhanced resistance to leaf blast, panicle blast and bacterial blight. In contrast, silencing of OsWRKY67 increased the susceptibility to blast and bacterial blight diseases. RNA-seq analysis indicated that OsWRKY67 induces the transcription of a set of defense-related genes including the ones involved in the salicylic acid (SA)-dependent pathway. Consistent with this, the OsWRKY67-overexpressing plants accumulated higher amounts of endogenous SA, whereas lower endogenous SA levels were observed in OsWRKY67-silenced plants relative to wild-type Nipponbare plants before and after pathogen attack. Moreover, we also observed that OsWRKY67 directly binds to the promoters of PR1a and PR10 to activate their expression.

CONCLUSIONS: These results together suggest the positive role of OsWRKY67 in regulating rice responses to leaf blast, panicle blast and bacterial blight disease. Furthermore, conferring resistance to two major diseases makes it a good target of molecular breeding for crop improvement in rice.}, } @article {pmid30367630, year = {2018}, author = {Li, S and Chen, Z and Zhao, N and Wang, Y and Nie, H and Hua, J}, title = {The comparison of four mitochondrial genomes reveals cytoplasmic male sterility candidate genes in cotton.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {775}, pmid = {30367630}, issn = {1471-2164}, support = {31671741//National Natural Science Foundation of China/ ; 2016YFD0100203//National Key R & D Program for Crop Breeding/ ; }, abstract = {BACKGROUND: The mitochondrial genomes of higher plants vary remarkably in size, structure and sequence content, as demonstrated by the accumulation and activity of repetitive DNA sequences. Incompatibility between mitochondrial genome and nuclear genome leads to non-functional male reproductive organs and results in cytoplasmic male sterility (CMS). CMS has been used to produce F1 hybrid seeds in a variety of plant species.

RESULTS: Here we compared the mitochondrial genomes (mitogenomes) of Gossypium hirsutum sterile male lines CMS-2074A and CMS-2074S, as well as their restorer and maintainer lines. First, we noticed the mitogenome organization and sequences were conserved in these lines. Second, we discovered the mitogenomes of 2074A and 2074S underwent large-scale substitutions and rearrangements. Actually, there were five and six unique chimeric open reading frames (ORFs) in 2074A and 2074S, respectively, which were derived from the recombination between unique repetitive sequences and nearby functional genes. Third, we found out four chimeric ORFs that were differentially transcribed in sterile line (2074A) and fertile-restored line.

CONCLUSIONS: These four novel and recombinant ORFs are potential candidates that confer CMS character in 2074A. In addition, our observations suggest that CMS in cotton is associated with the accelerated rates of rearrangement, and that novel expression products are derived from recombinant ORFs.}, } @article {pmid30367626, year = {2018}, author = {Gao, B and Chen, M and Li, X and Liang, Y and Zhu, F and Liu, T and Zhang, D and Wood, AJ and Oliver, MJ and Zhang, J}, title = {Evolution by duplication: paleopolyploidy events in plants reconstructed by deciphering the evolutionary history of VOZ transcription factors.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {256}, pmid = {30367626}, issn = {1471-2229}, support = {1638972//Directorate for Biological Sciences/ ; }, mesh = {*Evolution, Molecular ; Gene Duplication ; *Genome, Plant ; Phylogeny ; Plant Proteins/classification/*genetics ; *Polyploidy ; Solanaceae/genetics ; Species Specificity ; Transcription Factors/classification/*genetics ; }, abstract = {BACKGROUND: Facilitated by the rapid progress of sequencing technology, comparative genomic studies in plants have unveiled recurrent whole genome duplication (i.e. polyploidization) events throughout plant evolution. The evolutionary past of plant genes should be analyzed in a background of recurrent polyploidy events in distinctive plant lineages. The Vascular Plant One Zinc-finger (VOZ) gene family encode transcription factors associated with a number of important traits including control of flowering time and photoperiodic pathways, but the evolutionary trajectory of this gene family remains uncharacterized.

RESULTS: In this study, we deciphered the evolutionary history of the VOZ gene family by analyses of 107 VOZ genes in 46 plant genomes using integrated methods: phylogenic reconstruction, Ks-based age estimation and genomic synteny comparisons. By scrutinizing the VOZ gene family phylogeny the core eudicot γ event was well circumscribed, and relics of the precommelinid τ duplication event were detected by incorporating genes from oil palm and banana. The more recent T and ρ polyploidy events, closely coincident with the species diversification in Solanaceae and Poaceae, respectively, were also identified. Other important polyploidy events captured included the "salicoid" event in poplar and willow, the "early legume" and "soybean specific" events in soybean, as well as the recent polyploidy event in Physcomitrella patens. Although a small transcription factor gene family, the evolutionary history of VOZ genes provided an outstanding record of polyploidy events in plants. The evolutionary past of VOZ gene family demonstrated a close correlation with critical plant polyploidy events which generated species diversification and provided answer to Darwin's "abominable mystery".

CONCLUSIONS: We deciphered the evolutionary history of VOZ transcription factor family in plants and ancestral polyploidy events in plants were recapitulated simultaneously. This analysis allowed for the generation of an idealized plant gene tree demonstrating distinctive retention and fractionation patterns following polyploidy events.}, } @article {pmid30367619, year = {2018}, author = {Kiani, M and Szczepaniec, A}, title = {Effects of sugarcane aphid herbivory on transcriptional responses of resistant and susceptible sorghum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {774}, pmid = {30367619}, issn = {1471-2164}, support = {TEX09638//USDA NIFA/ ; 3072-22000-016-00D//USDA-ARS/ ; }, abstract = {BACKGROUND: Sugarcane aphid (Melanaphis sacchari) outbreaks in sorghum that were first reported in 2013 are now the most significant threat to this crop in all major sorghum production areas in the U.S. The outcomes of interactions between sugarcane aphid and sorghum and thus the severity of the outbreaks depend on sorghum genotype and potentially also on the phenology of sorghum. Mechanisms underlying these interactions are not known, however. Thus, the goal of this research was to characterize transcriptional changes in a commercially available resistant and a susceptible genotype of sorghum at 2- and 6-wk post-emergence exposed to M. sacchari herbivory. The effects of sorghum age and genotype on the daily change in aphid densities were also evaluated in separate greenhouse experiments.

RESULTS: A higher number of diffentially expressed genes (DEGs) was recovered from the 2-wk plants exposed to aphid herbivory compared to the 6-wk plants across genotypes. Further, gene ontology and pathway analysis indicated a suite of transcriptional changes in the resistant genotype that were weak or absent in the susceptible sorghum. Specifically, the aphid-resistant genotype exposed to M. sacchari up-regulated several genes involved in defense, which was particularly evident in the 2-wk plants that showed the most robust transcriptional responses. These transcriptional changes in the younger resistant sorghum were characterized by induction of hormone-signaling pathways, pathways coding for secondary metabolites, glutathion metabolism, and plant-pathogen interaction. Furthermore, the 2-wk resistant plants appeared to compensate for the effects of oxidative stress induced by sugarcane aphid herbivory with elevated expression of genes involved in detoxification. These transcriptional responses were reflected in the aphid population growth, which was significantly faster in the susceptible and older sorghum than in the resistant and younger plants.

CONCLUSION: This experiment provided the first insights into molecular mechanisms underlying lower population growth of M. sacchari on the resistant sorghum genotype. Further, it appears that the younger resistant sorghum was able to mount a robust defense response following aphid herbivory, which was much weaker in the older sorghum. Several pathways and specific genes provide specific clues into the mechanisms underlying host plant resistance to this invasive insect.}, } @article {pmid30367616, year = {2018}, author = {Sarker, U and Oba, S}, title = {Drought stress enhances nutritional and bioactive compounds, phenolic acids and antioxidant capacity of Amaranthus leafy vegetable.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {258}, pmid = {30367616}, issn = {1471-2229}, mesh = {Amaranthus/genetics/*physiology ; Antioxidants/*metabolism/pharmacology ; Ascorbic Acid/metabolism ; Bangladesh ; Carotenoids/metabolism ; Chlorophyll/metabolism ; Dehydration ; *Droughts ; Flavonoids/*metabolism ; Genotype ; Hydroxybenzoates/*metabolism ; Minerals/analysis ; Pigments, Biological/metabolism ; Plant Leaves/physiology ; Polyphenols/metabolism ; }, abstract = {BACKGROUND: Bioactive compounds, vitamins, phenolic acids, flavonoids of A. tricolor are the sources of natural antioxidant that had a great importance for the food industry as these detoxify ROS in the human body. These natural antioxidants protect human from many diseases such as cancer, arthritis, emphysema, retinopathy, neuro-degenerative cardiovascular diseases, atherosclerosis and cataracts. Moreover, previous literature has shown that drought stress elevated bioactive compounds, vitamins, phenolics, flavonoids and antioxidant activity in many leafy vegetables. Hence, we study the nutritional and bioactive compounds, phenolic acids, flavonoids and antioxidant capacity of amaranth under drought stress for evaluation of the significant contribution of these compounds in the human diet.

RESULTS: The genotype VA3 was assessed at four drought stress levels that significantly affected nutritional and bioactive compounds, phenolic acids, flavonoids and antioxidant capacity. Protein, ash, energy, dietary fiber, Ca, K, Cu, S, Mg, Mn, Mo, Na, B content, total carotenoids, TFC, vitamin C, TPC, TAC (DPPH), betacarotene, TAC (ABTS+), sixteen phenolic acids and flavonoids were remarkably increased with the severity of drought stress. At moderate and severe drought stress conditions, the increments of all these components were more preponderant. Trans-cinnamic acid was newly identified phenolic acid in A. tricolor. Salicylic acid, vanilic acid, gallic acid, chlorogenic acid, Trans-cinnamic acid, rutin, isoquercetin, m-coumaric acid and p-hydroxybenzoic acid were the most abundant phenolic compounds in this genotype.

CONCLUSIONS: In A. tricolor, drought stress enhanced the quantitative and qualitative improvement of nutritional and bioactive compounds, phenolic acids, flavonoids and antioxidants. Hence, farmers of semi-arid and dry areas of the world could be able to grow amaranth as a substitute crop.}, } @article {pmid30367612, year = {2018}, author = {Lu, PP and Zheng, WJ and Wang, CT and Shi, WY and Fu, JD and Chen, M and Chen, J and Zhou, YB and Xi, YJ and Xu, ZS}, title = {Wheat Bax Inhibitor-1 interacts with TaFKBP62 and mediates response to heat stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {259}, pmid = {30367612}, issn = {1471-2229}, support = {2018ZX0800909B//National Transgenic Key Project of the Ministry of Agriculture of China/ ; 2016ZX08002-002//National Transgenic Key Project of the Ministry of Agriculture of China/ ; 2014YB079//Fundamental Research Funds for the Central Universities/ ; 2016YFD0100600//National Key Research and Development Program of China/ ; }, mesh = {Arabidopsis/genetics/physiology ; Arabidopsis Proteins/genetics/metabolism ; Endoplasmic Reticulum/metabolism ; Gene Expression Regulation, Plant ; Heat-Shock Response/genetics/*physiology ; Intracellular Membranes/metabolism ; Membrane Proteins/genetics/metabolism ; Mutation ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; Protein Interaction Domains and Motifs ; Triticum/genetics/*physiology ; Up-Regulation ; }, abstract = {BACKGROUND: Heat stress is a severe environmental stress that affects plant growth and reduces yield. Bax inhibitor-1 (BI-1) is a cytoprotective protein that is involved in the response to biotic and abiotic stresses. The Arabidopsis (Arabidopsis thaliana) BI-1 mutants atbi1-1 and atbi1-2 are hypersensitive to heat stress, and AtBI-1 overexpression rescues thermotolerance deficiency in atbi1 plants. Nevertheless, the mechanism of BI-1 in plant thermotolerance is still unclear.

RESULTS: We identified a wheat (Triticum aestivum L.) BI-1 gene, TaBI-1.1, which was highly upregulated in an RNA sequencing (RNA-seq) analysis of heat-treated wheat. The upregulation of TaBI-1.1 under heat stress was further demonstrated by real time quantitative PCR (qRT-PCR) and β-glucuronidase (GUS) staining. Compared with the wild type Col-0, the atbi1-2 mutant is hypersensitive to heat stress, and constitutive expression of TaBI-1.1 in atbi1-2 (35S::TaBI-1.1/ atbi1-2) rescued the deficiency of atbi1-2 under heat stress. Furthermore, we identified TaFKBP62 as a TaBI-1.1-interacting protein that co-localized with TaBI-1.1 on the endoplasmic reticulum (ER) membrane and enhanced heat stress tolerance. Additionally, HSFA2, HSFB1, ROF1, HSP17.4B, HSP17.6A, HSP17.8, HSP70B, and HSP90.1 expression levels were suppressed in atbi1-2 plants under heat stress. In contrast, 35S::TaBI-1.1/atbi1-2 relieved the inhibitory effect of AtBI-1 loss of function.

CONCLUSIONS: TaBI-1.1 interacted with TaFKBP62 and co-localized with TaFKBP62 on the ER membrane. Both TaBI-1.1 and AtBI-1 regulated the expression of heat-responsive genes and were conserved in plant thermotolerance.}, } @article {pmid30367598, year = {2018}, author = {Shi, JY and Huang, H and Zhang, YN and Cao, JB and Yiu, SM}, title = {BMCMDA: a novel model for predicting human microbe-disease associations via binary matrix completion.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {281}, pmid = {30367598}, issn = {1471-2105}, mesh = {*Algorithms ; *Bacteria ; Bacterial Physiological Phenomena ; Computational Biology/*methods ; *Disease ; Host-Pathogen Interactions ; Humans ; *Microbiota ; *Models, Biological ; Risk Factors ; }, abstract = {BACKGROUND: Human Microbiome Project reveals the significant mutualistic influence between human body and microbes living in it. Such an influence lead to an interesting phenomenon that many noninfectious diseases are closely associated with diverse microbes. However, the identification of microbe-noninfectious disease associations (MDAs) is still a challenging task, because of both the high cost and the limitation of microbe cultivation. Thus, there is a need to develop fast approaches to screen potential MDAs. The growing number of validated MDAs enables us to meet the demand in a new insight. Computational approaches, especially machine learning, are promising to predict MDA candidates rapidly among a large number of microbe-disease pairs with the advantage of no limitation on microbe cultivation. Nevertheless, a few computational efforts at predicting MDAs are made so far.

RESULTS: In this paper, grouping a set of MDAs into a binary MDA matrix, we propose a novel predictive approach (BMCMDA) based on Binary Matrix Completion to predict potential MDAs. The proposed BMCMDA assumes that the incomplete observed MDA matrix is the summation of a latent parameterizing matrix and a noising matrix. It also assumes that the independently occurring subscripts of observed entries in the MDA matrix follows a binomial model. Adopting a standard mean-zero Gaussian distribution for the nosing matrix, we model the relationship between the parameterizing matrix and the MDA matrix under the observed microbe-disease pairs as a probit regression. With the recovered parameterizing matrix, BMCMDA deduces how likely a microbe would be associated with a particular disease. In the experiment under leave-one-out cross-validation, it exhibits the inspiring performance (AUC = 0.906, AUPR =0.526) and demonstrates its superiority by ~ 7% and ~ 5% improvements in terms of AUC and AUPR respectively in the comparison with the pioneering approach KATZHMDA.

CONCLUSIONS: Our BMCMDA provides an effective approach for predicting MDAs and can be also extended to other similar predicting tasks of binary relationship (e.g. protein-protein interaction, drug-target interaction).}, } @article {pmid30367597, year = {2018}, author = {Jackman, SD and Coombe, L and Chu, J and Warren, RL and Vandervalk, BP and Yeo, S and Xue, Z and Mohamadi, H and Bohlmann, J and Jones, SJM and Birol, I}, title = {Tigmint: correcting assembly errors using linked reads from large molecules.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {393}, pmid = {30367597}, issn = {1471-2105}, mesh = {Chromosomes, Human/genetics ; Genome, Human ; Genomics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Nanopores ; Repetitive Sequences, Nucleic Acid ; *Software ; }, abstract = {BACKGROUND: Genome sequencing yields the sequence of many short snippets of DNA (reads) from a genome. Genome assembly attempts to reconstruct the original genome from which these reads were derived. This task is difficult due to gaps and errors in the sequencing data, repetitive sequence in the underlying genome, and heterozygosity. As a result, assembly errors are common. In the absence of a reference genome, these misassemblies may be identified by comparing the sequencing data to the assembly and looking for discrepancies between the two. Once identified, these misassemblies may be corrected, improving the quality of the assembled sequence. Although tools exist to identify and correct misassemblies using Illumina paired-end and mate-pair sequencing, no such tool yet exists that makes use of the long distance information of the large molecules provided by linked reads, such as those offered by the 10x Genomics Chromium platform. We have developed the tool Tigmint to address this gap.

RESULTS: To demonstrate the effectiveness of Tigmint, we applied it to assemblies of a human genome using short reads assembled with ABySS 2.0 and other assemblers. Tigmint reduced the number of misassemblies identified by QUAST in the ABySS assembly by 216 (27%). While scaffolding with ARCS alone more than doubled the scaffold NGA50 of the assembly from 3 to 8 Mbp, the combination of Tigmint and ARCS improved the scaffold NGA50 of the assembly over five-fold to 16.4 Mbp. This notable improvement in contiguity highlights the utility of assembly correction in refining assemblies. We demonstrate the utility of Tigmint in correcting the assemblies of multiple tools, as well as in using Chromium reads to correct and scaffold assemblies of long single-molecule sequencing.

CONCLUSIONS: Scaffolding an assembly that has been corrected with Tigmint yields a final assembly that is both more correct and substantially more contiguous than an assembly that has not been corrected. Using single-molecule sequencing in combination with linked reads enables a genome sequence assembly that achieves both a high sequence contiguity as well as high scaffold contiguity, a feat not currently achievable with either technology alone.}, } @article {pmid30367596, year = {2018}, author = {Wang, D and Wang, L}, title = {GRSR: a tool for deriving genome rearrangement scenarios from multiple unichromosomal genome sequences.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {291}, doi = {10.1186/s12859-018-2268-1}, pmid = {30367596}, issn = {1471-2105}, mesh = {*Algorithms ; Chromosome Mapping/*methods ; *Gene Rearrangement ; *Genome, Bacterial ; Mycobacterium tuberculosis/*genetics ; Shewanella/*genetics ; Translocation, Genetic ; }, abstract = {BACKGROUND: Genome rearrangements describe changes in the genetic linkage relationship of large chromosomal regions, involving reversals, transpositions, block interchanges, deletions, insertions, fissions, fusions and translocations etc. Many algorithms for calculating rearrangement scenarios between two genomes have been proposed. Very often, the calculated rearrangement scenario is not unique for the same pair of permutations. Hence, how to decide which calculated rearrangement scenario is more biologically meaningful becomes an essential task. Up to now, several mechanisms for genome rearrangements have been studied. One important theory is that genome rearrangement may be mediated by repeats, especially for reversal events. Many reversal regions are found to be flanked by a pair of inverted repeats. As a result, whether there are repeats at the breakpoints of the calculated rearrangement events can shed a light on deciding whether the calculated rearrangement events is biologically meaningful. To our knowledge, there is no tool which can automatically identify rearrangement events and check whether there exist repeats at the breakpoints of each calculated rearrangement event.

RESULTS: In this paper, we describe a new tool named GRSR which allows us to compare multiple unichromosomal genomes to identify "independent" (obvious) rearrangement events such as reversals, (inverted) block interchanges and (inverted) transpositions and automatically searches for repeats at the breakpoints of each rearrangement event. We apply our tool on the complete genomes of 28 Mycobacterium tuberculosis strains and 24 Shewanella strains respectively. In both Mycobacterium tuberculosis and Shewanella strains, our tool finds many reversal regions flanked by a pair of inverted repeats. In particular, the GRSR tool also finds an inverted transposition and an inverted block interchange in Shewanella, where the repeats at the ends of rearrangement regions remain unchanged after the rearrangement event. To our knowledge, this is the first time such a phenomenon for inverted transposition and inverted block interchange is reported in Shewanella.

CONCLUSIONS: From the calculated results, there are many examples supporting the theory that the existence of repeats at the breakpoints of a rearrangement event can make the sequences at the breakpoints remain unchanged before and after the rearrangement events, suggesting that the conservation of ends could possibly be a popular phenomenon in many types of genome rearrangement events.}, } @article {pmid30367595, year = {2018}, author = {Kulkarni, N and Alessandrì, L and Panero, R and Arigoni, M and Olivero, M and Ferrero, G and Cordero, F and Beccuti, M and Calogero, RA}, title = {Reproducible bioinformatics project: a community for reproducible bioinformatics analysis pipelines.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {349}, doi = {10.1186/s12859-018-2296-x}, pmid = {30367595}, issn = {1471-2105}, mesh = {Computational Biology/*methods ; Humans ; MicroRNAs/genetics ; Reproducibility of Results ; Software ; User-Computer Interface ; Workflow ; }, abstract = {BACKGROUND: Reproducibility of a research is a key element in the modern science and it is mandatory for any industrial application. It represents the ability of replicating an experiment independently by the location and the operator. Therefore, a study can be considered reproducible only if all used data are available and the exploited computational analysis workflow is clearly described. However, today for reproducing a complex bioinformatics analysis, the raw data and the list of tools used in the workflow could be not enough to guarantee the reproducibility of the results obtained. Indeed, different releases of the same tools and/or of the system libraries (exploited by such tools) might lead to sneaky reproducibility issues.

RESULTS: To address this challenge, we established the Reproducible Bioinformatics Project (RBP), which is a non-profit and open-source project, whose aim is to provide a schema and an infrastructure, based on docker images and R package, to provide reproducible results in Bioinformatics. One or more Docker images are then defined for a workflow (typically one for each task), while the workflow implementation is handled via R-functions embedded in a package available at github repository. Thus, a bioinformatician participating to the project has firstly to integrate her/his workflow modules into Docker image(s) exploiting an Ubuntu docker image developed ad hoc by RPB to make easier this task. Secondly, the workflow implementation must be realized in R according to an R-skeleton function made available by RPB to guarantee homogeneity and reusability among different RPB functions. Moreover she/he has to provide the R vignette explaining the package functionality together with an example dataset which can be used to improve the user confidence in the workflow utilization.

CONCLUSIONS: Reproducible Bioinformatics Project provides a general schema and an infrastructure to distribute robust and reproducible workflows. Thus, it guarantees to final users the ability to repeat consistently any analysis independently by the used UNIX-like architecture.}, } @article {pmid30367594, year = {2018}, author = {Frasca, M and Grossi, G and Gliozzo, J and Mesiti, M and Notaro, M and Perlasca, P and Petrini, A and Valentini, G}, title = {A GPU-based algorithm for fast node label learning in large and unbalanced biomolecular networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {353}, doi = {10.1186/s12859-018-2301-4}, pmid = {30367594}, issn = {1471-2105}, mesh = {*Algorithms ; Animals ; *Computer Graphics ; Gene Ontology ; *Gene Regulatory Networks ; Humans ; Mice ; Protein Interaction Maps/genetics ; Proteins/genetics ; Saccharomyces cerevisiae/genetics ; Time Factors ; }, abstract = {BACKGROUND: Several problems in network biology and medicine can be cast into a framework where entities are represented through partially labeled networks, and the aim is inferring the labels (usually binary) of the unlabeled part. Connections represent functional or genetic similarity between entities, while the labellings often are highly unbalanced, that is one class is largely under-represented: for instance in the automated protein function prediction (AFP) for most Gene Ontology terms only few proteins are annotated, or in the disease-gene prioritization problem only few genes are actually known to be involved in the etiology of a given disease. Imbalance-aware approaches to accurately predict node labels in biological networks are thereby required. Furthermore, such methods must be scalable, since input data can be large-sized as, for instance, in the context of multi-species protein networks.

RESULTS: We propose a novel semi-supervised parallel enhancement of COSNET, an imbalance-aware algorithm build on Hopfield neural model recently suggested to solve the AFP problem. By adopting an efficient representation of the graph and assuming a sparse network topology, we empirically show that it can be efficiently applied to networks with millions of nodes. The key strategy to speed up the computations is to partition nodes into independent sets so as to process each set in parallel by exploiting the power of GPU accelerators. This parallel technique ensures the convergence to asymptotically stable attractors, while preserving the asynchronous dynamics of the original model. Detailed experiments on real data and artificial big instances of the problem highlight scalability and efficiency of the proposed method.

CONCLUSIONS: By parallelizing COSNET we achieved on average a speed-up of 180x in solving the AFP problem in the S. cerevisiae, Mus musculus and Homo sapiens organisms, while lowering memory requirements. In addition, to show the potential applicability of the method to huge biomolecular networks, we predicted node labels in artificially generated sparse networks involving hundreds of thousands to millions of nodes.}, } @article {pmid30367593, year = {2018}, author = {Kundu, S and Bansal, MS}, title = {On the impact of uncertain gene tree rooting on duplication-transfer-loss reconciliation.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {290}, doi = {10.1186/s12859-018-2269-0}, pmid = {30367593}, issn = {1471-2105}, mesh = {*Algorithms ; *Evolution, Molecular ; *Gene Duplication ; *Gene Transfer, Horizontal ; Genomics/*methods ; *Multigene Family ; *Phylogeny ; Software ; Uncertainty ; }, abstract = {BACKGROUND: Duplication-Transfer-Loss (DTL) reconciliation is a powerful and increasingly popular technique for studying the evolution of microbial gene families. DTL reconciliation requires the use of rooted gene trees to perform the reconciliation with the species tree, and the standard technique for rooting gene trees is to assign a root that results in the minimum reconciliation cost across all rootings of that gene tree. However, even though it is well understood that many gene trees have multiple optimal roots, only a single optimal root is randomly chosen to create the rooted gene tree and perform the reconciliation. This remains an important overlooked and unaddressed problem in DTL reconciliation, leading to incorrect evolutionary inferences. In this work, we perform an in-depth analysis of the impact of uncertain gene tree rooting on the computed DTL reconciliation and provide the first computational tools to quantify and negate the impact of gene tree rooting uncertainty on DTL reconciliation.

RESULTS: Our analysis of a large data set of over 4500 gene families from 100 species shows that a large fraction of gene trees have multiple optimal rootings, that these multiple roots often, but not always, appear closely clustered together in the same region of the gene tree, that many aspects of the reconciliation remain conserved across the multiple rootings, that gene tree error has a profound impact on the prevalence and structure of multiple optimal rootings, and that there are specific interesting patterns in the reconciliation of those gene trees that have multiple optimal roots.

CONCLUSIONS: Our results show that unrooted gene trees can be meaningfully reconciled and high-quality evolutionary information can be obtained from them even after accounting for multiple optimal rootings. In addition, the techniques and tools introduced in this paper make it possible to systematically avoid incorrect evolutionary inferences caused by incorrect or uncertain gene tree rooting. These tools have been implemented in the phylogenetic reconciliation software package RANGER-DTL 2.0, freely available from http://compbio.engr.uconn.edu/software/RANGER-DTL/ .}, } @article {pmid30367592, year = {2018}, author = {Fernández-Pérez, J and Nantón, A and Méndez, J}, title = {Sequence characterization of the 5S ribosomal DNA and the internal transcribed spacer (ITS) region in four European Donax species (Bivalvia: Donacidae).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {97}, pmid = {30367592}, issn = {1471-2156}, support = {AGL2016-75288-R AEI/FEDER, UE.//Ministerio de Economía y Competitividad (Spain)/ ; }, abstract = {BACKGROUND: The whole repeat unit of 5S rDNA and the internal transcribed spacer (ITS) of four European Donax species were analysed. After amplifying, cloning and sequencing several 5S and ITS units, their basic features and their variation were described. The phylogenetic usefulness of 5S and ITS sequences in the inference of evolutionary relationships among these wedge clams was also investigated.

RESULTS: The length of the 5S repeat presented little variation among species, except D. trunculus that differed from the rest of the Donax species in 170-210 bp. The deduced coding region covered 120 bp, and showed recognizable internal control regions (ICRs) involved in the transcription. The length of non-transcribed spacer region (NTS) ranged from 157 bp to 165 bp in Donax trunculus and from 335 bp to 367 bp in the other three species. The conservation degree of transcriptional regulatory regions was analysed revealing a conserved TATA-like box in the upstream region. Regarding ITS sequences, the four Donax species showed slight size differences among clones due to the variation occurring in the ITS1 and ITS2, except Donax variegatus did not display size differences in the ITS2. The total length of the ITS sequence ranged between 814 and 1014 bp. Resulting phylogenetic trees display that the two ribosomal DNA regions provide well-resolved phylogenies where the four European Donax species form a single clade receiving high support in nodes. The topology obtained with 5S sequences was in agreement with Donax evolutionary relationships inferred from several sequences of different nature in previous studies.

CONCLUSIONS: This is not only a basic research work, where new data and new knowledge is provided about Donax species, but also have allowed the authentication of these wedge clams and offers future applications to provide other genetic resources.}, } @article {pmid30367591, year = {2018}, author = {Kim, S and Choi, S and Yoon, JH and Kim, Y and Lee, S and Park, T}, title = {Drug response prediction model using a hierarchical structural component modeling method.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {288}, doi = {10.1186/s12859-018-2270-7}, pmid = {30367591}, issn = {1471-2105}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Antineoplastic Agents/pharmacology ; Biomarkers, Tumor/*metabolism ; Cohort Studies ; Female ; Humans ; Liver Neoplasms/drug therapy/*metabolism ; Male ; Mass Spectrometry/*methods ; Middle Aged ; *Models, Statistical ; Proteomics/*methods ; Sorafenib/*pharmacology ; }, abstract = {BACKGROUND: Component-based structural equation modeling methods are now widely used in science, business, education, and other fields. This method uses unobservable variables, i.e., "latent" variables, and structural equation model relationships between observable variables. Here, we applied this structural equation modeling method to biologically structured data. To identify candidate drug-response biomarkers, we first used proteomic peptide-level data, as measured by multiple reaction monitoring mass spectrometry (MRM-MS), for liver cancer patients. MRM-MS is a highly sensitive and selective method for proteomic targeted quantitation of peptide abundances in complex biological samples.

RESULTS: We developed a component-based drug response prediction model, having the advantage that it first combines collapsed peptide-level data into protein-level information, facilitating subsequent biological interpretation. Our model also uses an alternating least squares algorithm, to efficiently estimate both coefficients of peptides and proteins. This approach also considers correlations between variables, without constraint, by a multiple testing problem. Using estimated peptide and protein coefficients, we selected significant protein biomarkers by permutation testing, resulting in our model for predicting liver cancer response to the tyrosine kinase inhibitor sorafenib.

CONCLUSIONS: Using data from a cohort of liver cancer patients, we then "fine-tuned" our model to successfully predict drug responses, as demonstrated by a high area under the curve (AUC) score. Such drug response prediction models may eventually find clinical translation in identifying individual patients likely to respond to specific therapies.}, } @article {pmid30367590, year = {2018}, author = {Veeramani, B and Raymond, JW and Chanda, P}, title = {DeepSort: deep convolutional networks for sorting haploid maize seeds.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {289}, doi = {10.1186/s12859-018-2267-2}, pmid = {30367590}, issn = {1471-2105}, mesh = {*Algorithms ; Genotype ; *Haploidy ; *Neural Networks (Computer) ; Phenotype ; Plant Breeding ; Seeds/*genetics/growth & development ; Zea mays/*genetics/growth & development ; }, abstract = {BACKGROUND: Maize is a leading crop in the modern agricultural industry that accounts for more than 40% grain production worldwide. THe double haploid technique that uses fewer breeding generations for generating a maize line has accelerated the pace of development of superior commercial seed varieties and has been transforming the agricultural industry. In this technique the chromosomes of the haploid seeds are doubled and taken forward in the process while the diploids marked for elimination. Traditionally, selective visual expression of a molecular marker within the embryo region of a maize seed has been used to manually discriminate diploids from haploids. Large scale production of inbred maize lines within the agricultural industry would benefit from the development of computer vision methods for this discriminatory task. However the variability in the phenotypic expression of the molecular marker system and the heterogeneity arising out of the maize genotypes and image acquisition have been an enduring challenge towards such efforts.

RESULTS: In this work, we propose a novel application of a deep convolutional network (DeepSort) for the sorting of haploid seeds in these realistic settings. Our proposed approach outperforms existing state-of-the-art machine learning classifiers that uses features based on color, texture and morphology. We demonstrate the network derives features that can discriminate the embryo regions using the activations of the neurons in the convolutional layers. Our experiments with different architectures show that the performance decreases with the decrease in the depth of the layers.

CONCLUSION: Our proposed method DeepSort based on the convolutional network is robust to the variation in the phenotypic expression, shape of the corn seeds, and the embryo pose with respect to the camera. In the era of modern digital agriculture, deep learning and convolutional networks will continue to play an important role in advancing research and product development within the agricultural industry.}, } @article {pmid30367589, year = {2018}, author = {Tsao, HY and Chan, PY and Su, EC}, title = {Predicting diabetic retinopathy and identifying interpretable biomedical features using machine learning algorithms.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {283}, doi = {10.1186/s12859-018-2277-0}, pmid = {30367589}, issn = {1471-2105}, mesh = {Adult ; Aged ; Aged, 80 and over ; *Algorithms ; Decision Support Systems, Clinical ; Diabetes Mellitus, Type 2/*complications ; Diabetic Retinopathy/*diagnosis/etiology ; Female ; Humans ; *Machine Learning ; Male ; Middle Aged ; Neural Networks (Computer) ; ROC Curve ; Risk Factors ; }, abstract = {BACKGROUND: The risk factors of diabetic retinopathy (DR) were investigated extensively in the past studies, but it remains unknown which risk factors were more associated with the DR than others. If we can detect the DR related risk factors more accurately, we can then exercise early prevention strategies for diabetic retinopathy in the most high-risk population. The purpose of this study is to build a prediction model for the DR in type 2 diabetes mellitus using data mining techniques including the support vector machines, decision trees, artificial neural networks, and logistic regressions.

RESULTS: Experimental results demonstrated that prediction performance by support vector machines performed better than the other machine learning algorithms and achieved 79.5% and 0.839 in accuracy and area under the receiver operating characteristic curve using percentage split (i.e., data set divided into 80% as trainning and 20% as test), respectively. Evaluated by three-way data split scheme (i.e., data set divided into 60% as training, 20% as validation, and 20% as independent test), our method obtained slightly lower performance compared to percentage split, which suggested that three-way data split is a better way to evaluate the real performance and prevent overestimation. Moreover, we incorporated approaches proposed in previous studies to evaluate our data set and our prediction performance outperformed the other previous studies in most evaluation measures. This lends support to our assumption that appropriate machine learning algorithms combined with discriminative clinical features can effectively detect diabetic retinopathy.

CONCLUSIONS: Our method identifies use of insulin and duration of diabetes as novel interpretable features to assist with clinical decisions in identifying the high-risk populations for diabetic retinopathy. If duration of DM increases by 1 year, the odds ratio to have DMR is increased by 9.3%. The odds ratio to have DR is increased by 3.561 times for patients who use insulin compared to patients who do not use insulin. Our results can be used to facilitate development of clinical decision support systems for clinical practice in the future.}, } @article {pmid30367588, year = {2018}, author = {Casiraghi, E and Huber, V and Frasca, M and Cossa, M and Tozzi, M and Rivoltini, L and Leone, BE and Villa, A and Vergani, B}, title = {A novel computational method for automatic segmentation, quantification and comparative analysis of immunohistochemically labeled tissue sections.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {357}, doi = {10.1186/s12859-018-2302-3}, pmid = {30367588}, issn = {1471-2105}, mesh = {*Algorithms ; Biomarkers, Tumor/metabolism ; Computational Biology/*methods ; Decision Trees ; Humans ; Image Processing, Computer-Assisted/*methods ; Immunohistochemistry ; Software ; *Staining and Labeling ; Support Vector Machine ; }, abstract = {BACKGROUND: In the clinical practice, the objective quantification of histological results is essential not only to define objective and well-established protocols for diagnosis, treatment, and assessment, but also to ameliorate disease comprehension.

SOFTWARE: The software MIAQuant_Learn presented in this work segments, quantifies and analyzes markers in histochemical and immunohistochemical images obtained by different biological procedures and imaging tools. MIAQuant_Learn employs supervised learning techniques to customize the marker segmentation process with respect to any marker color appearance. Our software expresses the location of the segmented markers with respect to regions of interest by mean-distance histograms, which are numerically compared by measuring their intersection. When contiguous tissue sections stained by different markers are available, MIAQuant_Learn aligns them and overlaps the segmented markers in a unique image enabling a visual comparative analysis of the spatial distribution of each marker (markers' relative location). Additionally, it computes novel measures of markers' co-existence in tissue volumes depending on their density.

CONCLUSIONS: Applications of MIAQuant_Learn in clinical research studies have proven its effectiveness as a fast and efficient tool for the automatic extraction, quantification and analysis of histological sections. It is robust with respect to several deficits caused by image acquisition systems and produces objective and reproducible results. Thanks to its flexibility, MIAQuant_Learn represents an important tool to be exploited in basic research where needs are constantly changing.}, } @article {pmid30367587, year = {2018}, author = {A, M and Valle I, FD and G, C and D, R}, title = {Statistical modelling of CG interdistance across multiple organisms.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {355}, doi = {10.1186/s12859-018-2303-2}, pmid = {30367587}, issn = {1471-2105}, mesh = {Animals ; Chromosomes, Human/genetics ; DNA Methylation/genetics ; Dinucleoside Phosphates/*genetics ; Genome Size ; Humans ; Linear Models ; Mammals/genetics ; *Models, Statistical ; }, abstract = {BACKGROUND: Statistical approaches to genetic sequences have revealed helpful to gain deeper insight into biological and structural functionalities, using ideas coming from information theory and stochastic modelling of symbolic sequences. In particular, previous analyses on CG dinucleotide position along the genome allowed to highlight its epigenetic role in DNA methylation, showing a different distribution tail as compared to other dinucleotides. In this paper we extend the analysis to the whole CG distance distribution over a selected set of higher-order organisms. Then we apply the best fitting probability density function to a large range of organisms (>4400) of different complexity (from bacteria to mammals) and we characterize some emerging global features.

RESULTS: We find that the Gamma distribution is optimal for the selected subset as compared to a group of several distributions, chosen for their physical meaning or because recently used in literature for similar studies. The parameters of this distribution, when applied to our larger set of organisms, allows to highlight some biologically relavant features for the considered organism classes, that can be useful also for classification purposes.

CONCLUSIONS: The quantification of statistical properties of CG dinucleotide positioning along the genome is confirmed as a useful tool to characterize broad classes of organisms, spanning the whole range of biological complexity.}, } @article {pmid30367586, year = {2018}, author = {Zhou, X and Park, B and Choi, D and Han, K}, title = {A generalized approach to predicting protein-protein interactions between virus and host.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {568}, doi = {10.1186/s12864-018-4924-2}, pmid = {30367586}, issn = {1471-2164}, abstract = {BACKGROUND: Viral infection involves a large number of protein-protein interactions (PPIs) between virus and its host. These interactions range from the initial binding of viral coat proteins to host membrane receptor to the hijacking the host transcription machinery by viral proteins. Therefore, identifying PPIs between virus and its host helps understand the mechanism of viral infections and design antiviral drugs. Many computational methods have been developed to predict PPIs, but most of them are intended for PPIs within a species rather than PPIs across different species such as PPIs between virus and host.

RESULTS: In this study, we developed a prediction model of virus-host PPIs, which is applicable to new viruses and hosts. We tested the prediction model on independent datasets of virus-host PPIs, which were not used in training the model. Despite a low sequence similarity between proteins in training datasets and target proteins in test datasets, the prediction model showed a high performance comparable to the best performance of other methods for single virus-host PPIs.

CONCLUSIONS: Our method will be particularly useful to find PPIs between host and new viruses for which little information is available. The program and support data are available at http://bclab.inha.ac.kr/VirusHostPPI .}, } @article {pmid30367585, year = {2018}, author = {Bonnici, V and Caro, G and Constantino, G and Liuni, S and D'Elia, D and Bombieri, N and Licciulli, F and Giugno, R}, title = {Arena-Idb: a platform to build human non-coding RNA interaction networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {350}, doi = {10.1186/s12859-018-2298-8}, pmid = {30367585}, issn = {1471-2105}, mesh = {Databases, Genetic ; *Gene Regulatory Networks ; Humans ; RNA, Untranslated/*genetics ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: High throughput technologies have provided the scientific community an unprecedented opportunity for large-scale analysis of genomes. Non-coding RNAs (ncRNAs), for a long time believed to be non-functional, are emerging as one of the most important and large family of gene regulators and key elements for genome maintenance. Functional studies have been able to assign to ncRNAs a wide spectrum of functions in primary biological processes, and for this reason they are assuming a growing importance as a potential new family of cancer therapeutic targets. Nevertheless, the number of functionally characterized ncRNAs is still too poor if compared to the number of new discovered ncRNAs. Thus platforms able to merge information from available resources addressing data integration issues are necessary and still insufficient to elucidate ncRNAs biological roles.

RESULTS: In this paper, we describe a platform called Arena-Idb for the retrieval of comprehensive and non-redundant annotated ncRNAs interactions. Arena-Idb provides a framework for network reconstruction of ncRNA heterogeneous interactions (i.e., with other type of molecules) and relationships with human diseases which guide the integration of data, extracted from different sources, via mapping of entities and minimization of ambiguity.

CONCLUSIONS: Arena-Idb provides a schema and a visualization system to integrate ncRNA interactions that assists in discovering ncRNA functions through the extraction of heterogeneous interaction networks. The Arena-Idb is available at http://arenaidb.ba.itb.cnr.it.}, } @article {pmid30367584, year = {2018}, author = {Gao, J and Song, B and Hu, X and Yan, F and Wang, J}, title = {ConnectedAlign: a PPI network alignment method for identifying conserved protein complexes across multiple species.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {286}, doi = {10.1186/s12859-018-2271-6}, pmid = {30367584}, issn = {1471-2105}, mesh = {*Algorithms ; Animals ; Caenorhabditis elegans/metabolism ; Computational Biology/*methods ; Drosophila/metabolism ; Humans ; Protein Interaction Mapping/*methods ; Proteins/chemistry/*metabolism ; Saccharomyces cerevisiae/metabolism ; Species Specificity ; }, abstract = {BACKGROUND: In bioinformatics, network alignment algorithms have been applied to protein-protein interaction (PPI) networks to discover evolutionary conserved substructures at the system level. However, most previous methods aim to maximize the similarity of aligned proteins in pairwise networks, while concerning little about the feature of connectivity in these substructures, such as the protein complexes.

RESULTS: In this paper, we identify the problem of finding conserved protein complexes, which requires the aligned proteins in a PPI network to form a connected subnetwork. By taking the feature of connectivity into consideration, we propose ConnectedAlign, an efficient method to find conserved protein complexes from multiple PPI networks. The proposed method improves the coverage significantly without compromising of the consistency in the aligned results. In this way, the knowledge of protein complexes in well-studied species can be extended to that of poor-studied species.

CONCLUSIONS: We conducted extensive experiments on real PPI networks of four species, including human, yeast, fruit fly and worm. The experimental results demonstrate dominant benefits of the proposed method in finding protein complexes across multiple species.}, } @article {pmid30367583, year = {2018}, author = {Li, X and Chu, C and Pei, J and Măndoiu, I and Wu, Y}, title = {CircMarker: a fast and accurate algorithm for circular RNA detection.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {572}, doi = {10.1186/s12864-018-4926-0}, pmid = {30367583}, issn = {1471-2164}, abstract = {BACKGROUND: While RNA is often created from linear splicing during transcription, recent studies have found that non-canonical splicing sometimes occurs. Non-canonical splicing joins 3' and 5' and forms the so-called circular RNA. It is now believed that circular RNA plays important biological roles such as affecting susceptibility of some diseases. During the past several years, multiple experimental methods have been developed to enrich circular RNA while degrade linear RNA. Although several useful software tools for circular RNA detection have been developed as well, these tools are based on reads mapping may miss many circular RNA. Also, existing tools are slow for large data due to their dependence on reads mapping.

METHOD: In this paper, we present a new computational approach, named CircMarker, based on k-mers rather than reads mapping for circular RNA detection. CircMarker takes advantage of transcriptome annotation files to create the k-mer table for circular RNA detection.

RESULTS: Empirical results show that CircMarker outperforms existing tools in circular RNA detection on accuracy and efficiency in many simulated and real datasets.

CONCLUSIONS: We develop a new circular RNA detection method called CircMarker based on k-mer analysis. Our results on both simulation data and real data demonstrate that CircMarker runs much faster and can find more circular RNA with higher consensus-based sensitivity and high accuracy ratio compared with existing tools.}, } @article {pmid30367582, year = {2018}, author = {Chu, C and Pei, J and Wu, Y}, title = {An improved approach for reconstructing consensus repeats from short sequence reads.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {566}, doi = {10.1186/s12864-018-4920-6}, pmid = {30367582}, issn = {1471-2164}, abstract = {BACKGROUND: Repeat elements are important components of most eukaryotic genomes. Most existing tools for repeat analysis rely either on high quality reference genomes or existing repeat libraries. Thus, it is still challenging to do repeat analysis for species with highly repetitive or complex genomes which often do not have good reference genomes or annotated repeat libraries. Recently we developed a computational method called REPdenovo that constructs consensus repeat sequences directly from short sequence reads, which outperforms an existing tool called RepARK. One major issue with REPdenovo is that it doesn't perform well for repeats with relatively high divergence rates or low copy numbers. In this paper, we present an improved approach for constructing consensus repeats directly from short reads. Comparing with the original REPdenovo, the improved approach uses more repeat-related k-mers and improves repeat assembly quality using a consensus-based k-mer processing method.

RESULTS: We compare the performance of the new method with REPdenovo and RepARK on Human, Arabidopsis thaliana and Drosophila melanogaster short sequencing data. And the new method fully constructs more repeats in Repbase than the original REPdenovo and RepARK, especially for repeats of higher divergence rates and lower copy number. We also apply our new method on Hummingbird data which doesn't have a known repeat library, and it constructs many repeat elements that can be validated using PacBio long reads.

CONCLUSION: We propose an improved method for reconstructing repeat elements directly from short sequence reads. The results show that our new method can assemble more complete repeats than REPdenovo (and also RepARK). Our new approach has been implemented as part of the REPdenovo software package, which is available for download at https://github.com/Reedwarbler/REPdenovo .}, } @article {pmid30367581, year = {2018}, author = {Wu, G and Wan, X and Xu, B}, title = {A new estimation of protein-level false discovery rate.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {567}, doi = {10.1186/s12864-018-4923-3}, pmid = {30367581}, issn = {1471-2164}, abstract = {BACKGROUND: In mass spectrometry-based proteomics, protein identification is an essential task. Evaluating the statistical significance of the protein identification result is critical to the success of proteomics studies. Controlling the false discovery rate (FDR) is the most common method for assuring the overall quality of the set of identifications. Existing FDR estimation methods either rely on specific assumptions or rely on the two-stage calculation process of first estimating the error rates at the peptide-level, and then combining them somehow at the protein-level. We propose to estimate the FDR in a non-parametric way with less assumptions and to avoid the two-stage calculation process.

RESULTS: We propose a new protein-level FDR estimation framework. The framework contains two major components: the Permutation+BH (Benjamini-Hochberg) FDR estimation method and the logistic regression-based null inference method. In Permutation+BH, the null distribution of a sample is generated by searching data against a large number of permuted random protein database and therefore does not rely on specific assumptions. Then, p-values of proteins are calculated from the null distribution and the BH procedure is applied to the p-values to achieve the relationship of the FDR and the number of protein identifications. The Permutation+BH method generates the null distribution by the permutation method, which is inefficient for online identification. The logistic regression model is proposed to infer the null distribution of a new sample based on existing null distributions obtained from the Permutation+BH method.

CONCLUSIONS: In our experiment based on three public available datasets, our Permutation+BH method achieves consistently better performance than MAYU, which is chosen as the benchmark FDR calculation method for this study. The null distribution inference result shows that the logistic regression model achieves a reasonable result both in the shape of the null distribution and the corresponding FDR estimation result.}, } @article {pmid30367580, year = {2018}, author = {Wang, S and Wang, C and Wang, S and Ma, L}, title = {Big data analysis for evaluating bioinvasion risk.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {287}, doi = {10.1186/s12859-018-2272-5}, pmid = {30367580}, issn = {1471-2105}, mesh = {Animals ; Aquatic Organisms ; Data Mining/*methods ; *Ecosystem ; *Introduced Species ; *Models, Theoretical ; Oceans and Seas ; Ships ; *Transportation ; *Waste Disposal, Fluid ; }, abstract = {BACKGROUND: Global maritime trade plays an important role in the modern transportation industry. It brings significant economic profit along with bioinvasion risk. Species translocate and establish in a non-native area through ballast water and biofouling. Aiming at aquatic bioinvasion issue, people proposed various suggestions for bioinvasion management. Nonetheless, these suggestions only focus on the chance of a port been affected but ignore the port's ability to further spread the invaded species.

RESULTS: To tackle the issues of the existing work, we propose a biosecurity triggering mechanism, where the bioinvasion risk of a port is estimated according to both the invaded risk of a port and its power of being a stepping-stone. To compute the invaded risk, we utilize the automatic identification system data, the ballast water data and marine environmental data. According to the invaded risk of ports, we construct a species invasion network (SIN). The incoming bioinvasion risk is derived from invaded risk data while the invasion risk spreading capability of each port is evaluated by s-core decomposition of SIN.

CONCLUSIONS: We illustrate 100 ports in the world that have the highest bioinvasion risk when the invaded risk and stepping-stone bioinvasion risk are equally treated. There are two bioinvasion risk intensive regions, namely the Western Europe (including the Western European margin and the Mediterranean) and the Asia-Pacific, which are just the region with a high growth rate of non-indigenous species and the area that has been identified as a source for many of non-indigenous species discovered elsewhere (especially the Asian clam, which is assumed to be the most invasive species worldwide).}, } @article {pmid30367579, year = {2018}, author = {Peng, J and Xue, H and Hui, W and Lu, J and Chen, B and Jiang, Q and Shang, X and Wang, Y}, title = {An online tool for measuring and visualizing phenotype similarities using HPO.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {571}, doi = {10.1186/s12864-018-4927-z}, pmid = {30367579}, issn = {1471-2164}, abstract = {BACKGROUND: The Human Phenotype Ontology (HPO) is one of the most popular bioinformatics resources. Recently, HPO-based phenotype semantic similarity has been effectively applied to model patient phenotype data. However, the existing tools are revised based on the Gene Ontology (GO)-based term similarity. The design of the models are not optimized for the unique features of HPO. In addition, existing tools only allow HPO terms as input and only provide pure text-based outputs.

RESULTS: We present PhenoSimWeb, a web application that allows researchers to measure HPO-based phenotype semantic similarities using four approaches borrowed from GO-based similarity measurements. Besides, we provide a approach considering the unique properties of HPO. And, PhenoSimWeb allows text that describes phenotypes as input, since clinical phenotype data is always in text. PhenoSimWeb also provides a graphic visualization interface to visualize the resulting phenotype network.

CONCLUSIONS: PhenoSimWeb is an easy-to-use and functional online application. Researchers can use it to calculate phenotype similarity conveniently, predict phenotype associated genes or diseases, and visualize the network of phenotype interactions. PhenoSimWeb is available at http://120.77.47.2:8080.}, } @article {pmid30367578, year = {2018}, author = {Feng, H and Li, T and Zhang, X}, title = {Characterization of kinase gene expression and splicing profile in prostate cancer with RNA-Seq data.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {564}, doi = {10.1186/s12864-018-4925-1}, pmid = {30367578}, issn = {1471-2164}, abstract = {BACKGROUND: Alternative splicing is a ubiquitous post-transcriptional regulation mechanism in most eukaryotic genes. Aberrant splicing isoforms and abnormal isoform ratios can contribute to cancer development. Kinase genes are key regulators of multiple cellular processes. Many kinases are found to be oncogenic and have been intensively investigated in the study of cancer and drugs. RNA-Seq provides a powerful technology for genome-wide study of alternative splicing in cancer besides the conventional gene expression profiling. But this potential has not been fully demonstrated yet.

METHODS: We characterized the transcriptome profile of prostate cancer using RNA-Seq data from viewpoints of both differential expression and differential splicing, with an emphasis on kinase genes and their splicing variations. We built a pipeline to conduct differential expression and differential splicing analysis, followed by functional enrichment analysis. We performed kinase domain analysis to identify the functionally important candidate kinase gene in prostate cancer, and calculated the expression levels of isoforms to explore the function of isoform switching of kinase genes in prostate cancer.

RESULTS: We identified distinct gene groups from differential expression and splicing analyses, which suggested that alternative splicing adds another level to gene expression regulation. Enriched GO terms of differentially expressed and spliced kinase genes were found to play different roles in regulation of cellular metabolism. Function analysis on differentially spliced kinase genes showed that differentially spliced exons of these genes are significantly enriched in protein kinase domains. Among them, we found that gene CDK5 has isoform switching between prostate cancer and benign tissues, which may affect cancer development by changing androgen receptor (AR) phosphorylation. The observation was validated in another RNA-Seq dataset of prostate cancer cell lines.

CONCLUSIONS: Our work characterized the expression and splicing profiles of kinase genes in prostate cancer and proposed a hypothetical model on isoform switching of CDK5 and AR phosphorylation in prostate cancer. These findings bring new understanding to the role of alternatively spliced kinases in prostate cancer and also demonstrate the use of RNA-Seq data in studying alternative splicing in cancer.}, } @article {pmid30367577, year = {2018}, author = {Avni, E and Snir, S}, title = {Reconstruction of real and simulated phylogenies based on quartet plurality inference.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {570}, doi = {10.1186/s12864-018-4921-5}, pmid = {30367577}, issn = {1471-2164}, abstract = {BACKGROUND: Deciphering the history of life on Earth has long been regarded as one of the most central tasks in biology. In past years, widespread discordance between the evolutionary histories of different groups of orthologous genes of prokaryotes have been revealed, primarily due to horizontal gene transfers (HGTs). Nonetheless, evidence that support a strong tree-like signal of evolution have been uncovered, despite the presence of HGT events. Therefore, a challenging task is to distill this tree-like signal from the noise induced by all sources of non-tree-like events.

RESULTS: In this work we tackle this question, using real and simulated data. We first tighten a recent related theoretical result in this field. In a simulation study, we infer individual quartet topologies, and then use the inferred quartets to reconstruct simulated species trees. We demonstrate that accurate tree reconstruction is feasible despite surprisingly high rates of HGT. In a real data study, we construct phylogenies of two sets of prokaryotes, and show that our tree reconstruction scheme is comparable with (and complementary better than) other commonly used methods.

CONCLUSIONS: Using a blend of theoretical and empirical investigations, our study proves the feasibility of accurate quartet-based phylogenetic reconstruction, the vast impact of HGT events notwithstanding.}, } @article {pmid30367576, year = {2018}, author = {Yuan, Y and Shi, Y and Su, X and Zou, X and Luo, Q and Feng, DD and Cai, W and Han, ZG}, title = {Cancer type prediction based on copy number aberration and chromatin 3D structure with convolutional neural networks.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {565}, doi = {10.1186/s12864-018-4919-z}, pmid = {30367576}, issn = {1471-2164}, abstract = {BACKGROUND: With the developments of DNA sequencing technology, large amounts of sequencing data have been produced that provides unprecedented opportunities for advanced association studies between somatic mutations and cancer types/subtypes which further contributes to more accurate somatic mutation based cancer typing (SMCT). In existing SMCT methods however, the absence of high-level feature extraction is a major obstacle in improving the classification performance.

RESULTS: We propose DeepCNA, an advanced convolutional neural network (CNN) based classifier, which utilizes copy number aberrations (CNAs) and HiC data, to address this issue. DeepCNA first pre-process the CNA data by clipping, zero padding and reshaping. Then, the processed data is fed into a CNN classifier, which extracts high-level features for accurate classification. Experimental results on the COSMIC CNA dataset indicate that 2D CNN with both cell lines of HiC data lead to the best performance. We further compare DeepCNA with three widely adopted classifiers, and demonstrate that DeepCNA has at least 78% improvement of performance.

CONCLUSIONS: This paper demonstrates the advantages and potential of the proposed DeepCNA model for processing of somatic point mutation based gene data, and proposes that its usage may be extended to other complex genotype-phenotype association studies.}, } @article {pmid30367575, year = {2018}, author = {Moussa, M and Măndoiu, II}, title = {Single cell RNA-seq data clustering using TF-IDF based methods.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 6}, pages = {569}, doi = {10.1186/s12864-018-4922-4}, pmid = {30367575}, issn = {1471-2164}, abstract = {BACKGROUND: Single cell transcriptomics is critical for understanding cellular heterogeneity and identification of novel cell types. Leveraging the recent advances in single cell RNA sequencing (scRNA-Seq) technology requires novel unsupervised clustering algorithms that are robust to high levels of technical and biological noise and scale to datasets of millions of cells.

RESULTS: We present novel computational approaches for clustering scRNA-seq data based on the Term Frequency - Inverse Document Frequency (TF-IDF) transformation that has been successfully used in the field of text analysis.

CONCLUSIONS: Empirical experimental results show that TF-IDF methods consistently outperform commonly used scRNA-Seq clustering approaches.}, } @article {pmid30367574, year = {2018}, author = {Weitschek, E and Lauro, SD and Cappelli, E and Bertolazzi, P and Felici, G}, title = {CamurWeb: a classification software and a large knowledge base for gene expression data of cancer.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {354}, doi = {10.1186/s12859-018-2299-7}, pmid = {30367574}, issn = {1471-2105}, mesh = {Base Sequence ; *Gene Expression Regulation, Neoplastic ; Genes, Neoplasm ; Genome, Human ; Humans ; *Knowledge Bases ; Neoplasms/*genetics ; Sequence Analysis, RNA ; *Software ; }, abstract = {BACKGROUND: The high growth of Next Generation Sequencing data currently demands new knowledge extraction methods. In particular, the RNA sequencing gene expression experimental technique stands out for case-control studies on cancer, which can be addressed with supervised machine learning techniques able to extract human interpretable models composed of genes, and their relation to the investigated disease. State of the art rule-based classifiers are designed to extract a single classification model, possibly composed of few relevant genes. Conversely, we aim to create a large knowledge base composed of many rule-based models, and thus determine which genes could be potentially involved in the analyzed tumor. This comprehensive and open access knowledge base is required to disseminate novel insights about cancer.

RESULTS: We propose CamurWeb, a new method and web-based software that is able to extract multiple and equivalent classification models in form of logic formulas ("if then" rules) and to create a knowledge base of these rules that can be queried and analyzed. The method is based on an iterative classification procedure and an adaptive feature elimination technique that enables the computation of many rule-based models related to the cancer under study. Additionally, CamurWeb includes a user friendly interface for running the software, querying the results, and managing the performed experiments. The user can create her profile, upload her gene expression data, run the classification analyses, and interpret the results with predefined queries. In order to validate the software we apply it to all public available RNA sequencing datasets from The Cancer Genome Atlas database obtaining a large open access knowledge base about cancer. CamurWeb is available at http://bioinformatics.iasi.cnr.it/camurweb .

CONCLUSIONS: The experiments prove the validity of CamurWeb, obtaining many classification models and thus several genes that are associated to 21 different cancer types. Finally, the comprehensive knowledge base about cancer and the software tool are released online; interested researchers have free access to them for further studies and to design biological experiments in cancer research.}, } @article {pmid30367573, year = {2018}, author = {Zhu, K and Liu, X}, title = {A graph-based approach for proteoform identification and quantification using top-down homogeneous multiplexed tandem mass spectra.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {280}, doi = {10.1186/s12859-018-2273-4}, pmid = {30367573}, issn = {1471-2105}, mesh = {*Algorithms ; Chromatography, Liquid ; Histones/*metabolism ; Humans ; Molecular Weight ; *Protein Processing, Post-Translational ; Proteome/*analysis ; Proteomics/*methods ; Tandem Mass Spectrometry/*methods ; }, abstract = {BACKGROUND: Top-down homogeneous multiplexed tandem mass (HomMTM) spectra are generated from modified proteoforms of the same protein with different post-translational modification patterns. They are frequently observed in the analysis of ultramodified proteins, some proteoforms of which have similar molecular weights and cannot be well separated by liquid chromatography in mass spectrometry analysis.

RESULTS: We formulate the top-down HomMTM spectral identification problem as the minimum error k-splittable flow problem on graphs and propose a graph-based algorithm for the identification and quantification of proteoforms using top-down HomMTM spectra.

CONCLUSIONS: Experiments on a top-down mass spectrometry data set of the histone H4 protein showed that the proposed method identified many proteoform pairs that better explain the query spectra than single proteoforms.}, } @article {pmid30367572, year = {2018}, author = {Bonnici, V and Busato, F and Aldegheri, S and Akhmedov, M and Cascione, L and Carmena, AA and Bertoni, F and Bombieri, N and Kwee, I and Giugno, R}, title = {cuRnet: an R package for graph traversing on GPU.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {356}, doi = {10.1186/s12859-018-2310-3}, pmid = {30367572}, issn = {1471-2105}, mesh = {*Algorithms ; Computational Biology/*methods ; *Computer Graphics ; Computing Methodologies ; }, abstract = {BACKGROUND: R has become the de-facto reference analysis environment in Bioinformatics. Plenty of tools are available as packages that extend the R functionality, and many of them target the analysis of biological networks. Several algorithms for graphs, which are the most adopted mathematical representation of networks, are well-known examples of applications that require high-performance computing, and for which classic sequential implementations are becoming inappropriate. In this context, parallel approaches targeting GPU architectures are becoming pervasive to deal with the execution time constraints. Although R packages for parallel execution on GPUs are already available, none of them provides graph algorithms.

RESULTS: This work presents cuRnet, a R package that provides a parallel implementation for GPUs of the breath-first search (BFS), the single-source shortest paths (SSSP), and the strongly connected components (SCC) algorithms. The package allows offloading computing intensive applications to GPU devices for massively parallel computation and to speed up the runtime up to one order of magnitude with respect to the standard sequential computations on CPU. We have tested cuRnet on a benchmark of large protein interaction networks and for the interpretation of high-throughput omics data thought network analysis.

CONCLUSIONS: cuRnet is a R package to speed up graph traversal and analysis through parallel computation on GPUs. We show the efficiency of cuRnet applied both to biological network analysis, which requires basic graph algorithms, and to complex existing procedures built upon such algorithms.}, } @article {pmid30367571, year = {2018}, author = {Moscatelli, M and Manconi, A and Pessina, M and Fellegara, G and Rampoldi, S and Milanesi, L and Casasco, A and Gnocchi, M}, title = {An infrastructure for precision medicine through analysis of big data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {351}, doi = {10.1186/s12859-018-2300-5}, pmid = {30367571}, issn = {1471-2105}, mesh = {Algorithms ; Bayes Theorem ; *Big Data ; Biopsy ; Computer Simulation ; *Data Analysis ; Humans ; Machine Learning ; *Precision Medicine ; }, abstract = {BACKGROUND: Nowadays, the increasing availability of omics data, due to both the advancements in the acquisition of molecular biology results and in systems biology simulation technologies, provides the bases for precision medicine. Success in precision medicine depends on the access to healthcare and biomedical data. To this end, the digitization of all clinical exams and medical records is becoming a standard in hospitals. The digitization is essential to collect, share, and aggregate large volumes of heterogeneous data to support the discovery of hidden patterns with the aim to define predictive models for biomedical purposes. Patients' data sharing is a critical process. In fact, it raises ethical, social, legal, and technological issues that must be properly addressed.

RESULTS: In this work, we present an infrastructure devised to deal with the integration of large volumes of heterogeneous biological data. The infrastructure was applied to the data collected between 2010-2016 in one of the major diagnostic analysis laboratories in Italy. Data from three different platforms were collected (i.e., laboratory exams, pathological anatomy exams, biopsy exams). The infrastructure has been designed to allow the extraction and aggregation of both unstructured and semi-structured data. Data are properly treated to ensure data security and privacy. Specialized algorithms have also been implemented to process the aggregated information with the aim to obtain a precise historical analysis of the clinical activities of one or more patients. Moreover, three Bayesian classifiers have been developed to analyze examinations reported as free text. Experimental results show that the classifiers exhibit a good accuracy when used to analyze sentences related to the sample location, diseases presence and status of the illnesses.

CONCLUSIONS: The infrastructure allows the integration of multiple and heterogeneous sources of anonymized data from the different clinical platforms. Both unstructured and semi-structured data are processed to obtain a precise historical analysis of the clinical activities of one or more patients. Data aggregation allows to perform a series of statistical assessments required to answer complex questions that can be used in a variety of fields, such as predictive and precision medicine. In particular, studying the clinical history of patients that have developed similar pathologies can help to predict or individuate markers able to allow an early diagnosis of possible illnesses.}, } @article {pmid30367570, year = {2018}, author = {Peng, S and Cheng, M and Huang, K and Cui, Y and Zhang, Z and Guo, R and Zhang, X and Yang, S and Liao, X and Lu, Y and Zou, Q and Shi, B}, title = {Efficient computation of motif discovery on Intel Many Integrated Core (MIC) Architecture.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {282}, doi = {10.1186/s12859-018-2276-1}, pmid = {30367570}, issn = {1471-2105}, mesh = {Algorithms ; Computational Biology/*methods ; Computer Graphics ; Databases, Genetic ; Humans ; Internet ; *Nucleotide Motifs ; *Promoter Regions, Genetic ; *Regulatory Elements, Transcriptional ; *Software ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: Novel sequence motifs detection is becoming increasingly essential in computational biology. However, the high computational cost greatly constrains the efficiency of most motif discovery algorithms.

RESULTS: In this paper, we accelerate MEME algorithm targeted on Intel Many Integrated Core (MIC) Architecture and present a parallel implementation of MEME called MIC-MEME base on hybrid CPU/MIC computing framework. Our method focuses on parallelizing the starting point searching method and improving iteration updating strategy of the algorithm. MIC-MEME has achieved significant speedups of 26.6 for ZOOPS model and 30.2 for OOPS model on average for the overall runtime when benchmarked on the experimental platform with two Xeon Phi 3120 coprocessors.

CONCLUSIONS: Furthermore, MIC-MEME has been compared with state-of-arts methods and it shows good scalability with respect to dataset size and the number of MICs. Source code: https://github.com/hkwkevin28/MIC-MEME .}, } @article {pmid30367569, year = {2018}, author = {Li, L and Wan, J and Zheng, J and Wang, J}, title = {Biomedical event extraction based on GRU integrating attention mechanism.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {285}, doi = {10.1186/s12859-018-2275-2}, pmid = {30367569}, issn = {1471-2105}, mesh = {Attention ; Bacteria/*genetics/growth & development ; Data Mining/*methods ; *Environmental Microbiology ; Genes, Bacterial ; Humans ; *Natural Language Processing ; Publications ; }, abstract = {BACKGROUND: Biomedical event extraction is a crucial task in biomedical text mining. As the primary forum for international evaluation of different biomedical event extraction technologies, BioNLP Shared Task represents a trend in biomedical text mining toward fine-grained information extraction (IE). The fourth series of BioNLP Shared Task in 2016 (BioNLP-ST'16) proposed three tasks, in which the Bacteria Biotope event extraction (BB) task has been put forward in the earlier BioNLP-ST. Deep learning methods provide an effective way to automatically extract more complex features and achieve notable results in various natural language processing tasks.

RESULTS: The experimental results show that the presented approach can achieve an F-score of 57.42% in the test set, which outperforms previous state-of-the-art official submissions to BioNLP-ST 2016.

CONCLUSIONS: In this paper, we propose a novel Gated Recurrent Unit Networks framework integrating attention mechanism for extracting biomedical events between biotope and bacteria from biomedical literature, utilizing the corpus from the BioNLP'16 Shared Task on Bacteria Biotope task. The experimental results demonstrate the potential and effectiveness of the proposed framework.}, } @article {pmid30367568, year = {2018}, author = {Pai, TW and Li, KH and Yang, CH and Hu, CH and Lin, HJ and Wang, WD and Chen, YR}, title = {Multiple model species selection for transcriptomics analysis of non-model organisms.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 9}, pages = {284}, doi = {10.1186/s12859-018-2278-z}, pmid = {30367568}, issn = {1471-2105}, mesh = {Animals ; Bacteria/genetics ; Computational Biology/*methods ; Gene Expression Profiling/*methods ; Gene Ontology ; *Genome ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; *Models, Biological ; *Molecular Sequence Annotation ; Plants/genetics ; Reference Standards ; Species Specificity ; *Transcriptome ; }, abstract = {BACKGROUND: Transcriptomic sequencing (RNA-seq) related applications allow for rapid explorations due to their high-throughput and relatively fast experimental capabilities, providing unprecedented progress in gene functional annotation, gene regulation analysis, and environmental factor verification. However, with increasing amounts of sequenced reads and reference model species, the selection of appropriate reference species for gene annotation has become a new challenge.

METHODS: We proposed a novel approach for finding the most effective reference model species through taxonomic associations and ultra-conserved orthologous (UCO) gene comparisons among species. An online system for multiple species selection (MSS) for RNA-seq differential expression analysis was developed, and comprehensive genomic annotations from 291 reference model eukaryotic species were retrieved from the RefSeq, KEGG, and UniProt databases.

RESULTS: Using the proposed MSS pipeline, gene ontology and biological pathway enrichment analysis can be efficiently achieved, especially in the case of transcriptomic analysis of non-model organisms. The results showed that the proposed method solved problems related to limitations in annotation information and provided a roughly twenty-fold reduction in computational time, resulting in more accurate results than those of traditional approaches of using a single model reference species or the large non-redundant reference database.

CONCLUSIONS: Selection of appropriate reference model species helps to reduce missing annotation information, allowing for more comprehensive results than those obtained with a single model reference species. In addition, adequate model species selection reduces the computational time significantly while retaining the same order of accuracy. The proposed system indeed provides superior performance by selecting appropriate multiple species for transcriptomic analysis compared to traditional approaches.}, } @article {pmid30367567, year = {2018}, author = {Armano, G and Fotia, G and Manconi, A}, title = {BITS 2017: the annual meeting of the Italian Society of Bioinformatics.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 10}, pages = {352}, doi = {10.1186/s12859-018-2295-y}, pmid = {30367567}, issn = {1471-2105}, mesh = {*Computational Biology ; *Congresses as Topic ; Humans ; Italy ; Periodicals as Topic ; }, abstract = {This preface introduces the content of the BioMed Central journal Supplement related to the 14th annual meeting of the Bioinformatics Italian Society, held in Cagliari, Italy, from the 5th to the 7th of July, 2017.}, } @article {pmid30367177, year = {2018}, author = {}, title = {African genetics for human society.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1495}, doi = {10.1038/s41588-018-0277-7}, pmid = {30367177}, issn = {1546-1718}, } @article {pmid30367165, year = {2018}, author = {Rowley, MJ and Corces, VG}, title = {Organizational principles of 3D genome architecture.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {789-800}, doi = {10.1038/s41576-018-0060-8}, pmid = {30367165}, issn = {1471-0064}, support = {K99 GM127671/GM/NIGMS NIH HHS/United States ; R01 GM035463/GM/NIGMS NIH HHS/United States ; }, abstract = {Studies of 3D chromatin organization have suggested that chromosomes are hierarchically organized into large compartments composed of smaller domains called topologically associating domains (TADs). Recent evidence suggests that compartments are smaller than previously thought and that the transcriptional or chromatin state is responsible for interactions leading to the formation of small compartmental domains in all organisms. In vertebrates, CTCF forms loop domains, probably via an extrusion process involving cohesin. CTCF loops cooperate with compartmental domains to establish the 3D organization of the genome. The continuous extrusion of the chromatin fibre by cohesin may also be responsible for the establishment of enhancer-promoter interactions and stochastic aspects of the transcription process. These observations suggest that the 3D organization of the genome is an emergent property of chromatin and its components, and thus may not be only a determinant but also a consequence of its function.}, } @article {pmid30367164, year = {2018}, author = {Clyde, D}, title = {Spotlight on nucleosomes.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {738-739}, doi = {10.1038/s41576-018-0070-6}, pmid = {30367164}, issn = {1471-0064}, } @article {pmid30366952, year = {2018}, author = {Suren, T and Rutz, D and Mößmer, P and Merkel, U and Buchner, J and Rief, M}, title = {Single-molecule force spectroscopy reveals folding steps associated with hormone binding and activation of the glucocorticoid receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11688-11693}, pmid = {30366952}, issn = {1091-6490}, mesh = {Animals ; Heat-Shock Proteins/metabolism ; Humans ; Kinetics ; Ligands ; Molecular Chaperones/metabolism ; Protein Binding/physiology ; Protein Domains ; Protein Folding ; Receptors, Glucocorticoid/*metabolism/*ultrastructure ; Signal Transduction ; Single Molecule Imaging/*methods ; }, abstract = {The glucocorticoid receptor (GR) is a prominent nuclear receptor linked to a variety of diseases and an important drug target. Binding of hormone to its ligand binding domain (GR-LBD) is the key activation step to induce signaling. This process is tightly regulated by the molecular chaperones Hsp70 and Hsp90 in vivo. Despite its importance, little is known about GR-LBD folding, the ligand binding pathway, or the requirement for chaperone regulation. In this study, we have used single-molecule force spectroscopy by optical tweezers to unravel the dynamics of the complete pathway of folding and hormone binding of GR-LBD. We identified a "lid" structure whose opening and closing is tightly coupled to hormone binding. This lid is located at the N terminus without direct contacts to the hormone. Under mechanical load, apo-GR-LBD folds stably and readily without the need of chaperones with a folding free energy of [Formula: see text] The folding pathway is largely independent of the presence of hormone. Hormone binds only in the last step and lid closure adds an additional [Formula: see text] of free energy, drastically increasing the affinity. However, mechanical double-jump experiments reveal that, at zero force, GR-LBD folding is severely hampered by misfolding, slowing it to less than 1·s-1 From the force dependence of the folding rates, we conclude that the misfolding occurs late in the folding pathway. These features are important cornerstones for understanding GR activation and its tight regulation by chaperones.}, } @article {pmid30366951, year = {2018}, author = {Dutta, M and Diehl, MR and Onuchic, JN and Jana, B}, title = {Structural consequences of hereditary spastic paraplegia disease-related mutations in kinesin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10822-E10829}, pmid = {30366951}, issn = {1091-6490}, mesh = {Computational Biology/methods ; Computer Simulation ; Humans ; Kinesin/*genetics ; Models, Theoretical ; Mutation ; Protein Binding ; Spastic Paraplegia, Hereditary/*genetics ; }, abstract = {A wide range of mutations in the kinesin motor Kif5A have been linked to a neuronal disorder called hereditary spastic paraplegia (HSP). The position of these mutations can vary, and a range of different motile behaviors have been observed, indicating that the HSP mutants can alter distinct aspects of kinesin mechanochemistry. While focusing on four key HSP-associated mutants, this study examined the structural and dynamic perturbations that arise from these mutations using a series of different computational methods, ranging from bioinformatics analyses to all-atom simulations, that account for solvent effects explicitly. We show that two catalytic domain mutations (R280S and K253N) reduce the microtubule (MT) binding affinity of the kinesin head domains appreciably, while N256S has a much smaller impact. Bioinformatics analysis suggests that the stalk mutation A361V perturbs motor dimerization. Subsequent integration of these effects into a coarse-grained structure-based model of dimeric kinesin revealed that the order-disorder transition of the neck linker is substantially affected, indicating a hampered directionality and processivity of kinesin. The present analyses therefore suggest that, in addition to kinesin-MT binding and coiled-coil dimerization, HSP mutations affecting motor stepping transitions and processivity can lead to disease.}, } @article {pmid30366950, year = {2018}, author = {Brandvain, Y and Haig, D}, title = {Outbreeders pull harder in a parental tug-of-war.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11354-11356}, pmid = {30366950}, issn = {1091-6490}, } @article {pmid30366621, year = {2019}, author = {Escalera-Fanjul, X and Quezada, H and Riego-Ruiz, L and González, A}, title = {Whole-Genome Duplication and Yeast's Fruitful Way of Life.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {42-54}, doi = {10.1016/j.tig.2018.09.008}, pmid = {30366621}, issn = {0168-9525}, abstract = {Studies on the fate of Saccharomyces cerevisiae paralogous gene pairs that arose through a whole-genome duplication event have shown diversification of retained duplicated genes. Paralogous functional specialization often results in improved function and/or novel function that could contribute to the adaptation of the organism to a new lifestyle. Here, we analyze and discuss particular case studies of paralogous functional diversification that could have played a role in the acquisition of yeast fermentative metabolism.}, } @article {pmid30366310, year = {2018}, author = {Kanjee, U and Rangel, GW and Clark, MA and Duraisingh, MT}, title = {Molecular and cellular interactions defining the tropism of Plasmodium vivax for reticulocytes.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {109-115}, doi = {10.1016/j.mib.2018.10.002}, pmid = {30366310}, issn = {1879-0364}, abstract = {Plasmodium vivax is uniquely restricted to invading reticulocytes, the youngest of red blood cells. Parasite invasion relies on the sequential deployment of multiple parasite invasion ligands. Correct targeting of the host reticulocyte is mediated by two families of invasion ligands: the reticulocyte binding proteins (RBPs) and erythrocyte binding proteins (EBPs). The Duffy receptor has long been established as a key determinant for P. vivax invasion. However, recently, the RBP protein PvRBP2b has been shown to bind to transferrin receptor, which is expressed on reticulocytes but lost on normocytes, implicating the ligand-receptor in the reticulocyte tropism of P. vivax. Furthermore there is increasing evidence for P. vivax growth and sexual development in reticulocyte-enriched tissues such as the bone marrow.}, } @article {pmid30366088, year = {2019}, author = {Scott Chialvo, CH and White, BE and Reed, LK and Dyer, KA}, title = {A phylogenetic examination of host use evolution in the quinaria and testacea groups of Drosophila.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {233-243}, doi = {10.1016/j.ympev.2018.10.027}, pmid = {30366088}, issn = {1095-9513}, support = {R01 GM098856/GM/NIGMS NIH HHS/United States ; }, abstract = {Adaptive radiations provide an opportunity to examine complex evolutionary processes such as ecological specialization and speciation. While a well-resolved phylogenetic hypothesis is critical to completing such studies, the rapid rates of evolution in these groups can impede phylogenetic studies. Here we study the quinaria and testacea species groups of the immigrans-tripunctata radiation of Drosophila, which represent a recent adaptive radiation and are a developing model system for ecological genetics. We were especially interested in understanding host use evolution in these species. In order to infer a phylogenetic hypothesis for this group we sampled loci from both the nuclear genome and the mitochondrial DNA to develop a dataset of 43 protein-coding loci for these two groups along with their close relatives in the immigrans-tripunctata radiation. We used this dataset to examine their evolutionary relationships along with the evolution of feeding behavior. Our analysis recovers strong support for the monophyly of the testacea but not the quinaria group. Results from our ancestral state reconstruction analysis suggests that the ancestor of the testacea and quinaria groups exhibited mushroom-feeding. Within the quinaria group, we infer that transition to vegetative feeding occurred twice, and that this transition did not coincide with a genome-wide change in the rate of protein evolution.}, } @article {pmid30366087, year = {2019}, author = {Laakmann, S and Markhaseva, EL and Renz, J}, title = {Do molecular phylogenies unravel the relationships among the evolutionary young "Brafordian" families (Copepoda; Calanoida)?.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {330-345}, doi = {10.1016/j.ympev.2018.10.028}, pmid = {30366087}, issn = {1095-9513}, abstract = {Among the most derived calanoid copepod superfamily Clausocalanoidea about half of the genera belong to the so-called "Bradfordian" families that are defined by the presence of sensory setae at the maxilla and maxilliped. Many of these "Bradfordian" taxa are insufficiently well described, because their taxonomy is complicated and phylogenetic relationships are not completely resolved. We therefore aimed to unravel their phylogenetic relationships using molecular multi-gene analyses. We conducted molecular multi-gene analysis on 26 species from 15 genera representing all seven "Bradfordian" families using five gene fragments, the nuclear ribosomal 18S, 28S and internal transcribed spacer 2 DNA, and mitochondrial cytochrome c oxidase subunit I and cytochrome b. The monophyly of "Bradfordians" as one lineage in the superfamily Clausocalanoidea was supported by Maximum Likelihood and Bayesian Inference multi-gene analyses. Except for the support of species belonging to the same genus and specimens belonging to the same species, no phylogenetic relationships among genera and families were supported. The impossibility of resolving phylogenetic relationships among "Bradfordian" genera and families may be due to the young age or fast radiation of "Bradfordians" within the mostly derived calanoid superfamily Clausocalanoidea. Therefore, mutation rates might be not sufficient to track phylogenetic relationships. Evidence on phylogenetic relationships between genera and families remain unresolved after implementing integrated morphological and molecular taxonomic approaches.}, } @article {pmid30366086, year = {2019}, author = {Torres-Carvajal, O and Echevarría, LY and Lobos, SE and Venegas, PJ and Kok, PJR}, title = {Phylogeny, diversity and biogeography of Neotropical sipo snakes (Serpentes: Colubrinae: Chironius).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {315-329}, doi = {10.1016/j.ympev.2018.10.022}, pmid = {30366086}, issn = {1095-9513}, abstract = {Neotropical sipo snakes (Chironius) are large diurnal snakes with a long tail and big eyes that differ from other Neotropical snakes in having 10 or 12 dorsal scale rows at midbody. The 22 currently recognized species occur from Central America south to Uruguay and northeastern Argentina. Based on the largest geographical sampling to date including ∼90% of all species, we analyzed one nuclear and three mitochondrial genes using phylogenetic methods to (1) test the monophyly of Chironius and some of its widely distributed species; (2) identify lineages that could represent undescribed species; and (3) reconstruct ancestral distributions. Our best hypothesis placed C. grandisquamis (Chocoan Rainforest) + C. challenger (Pantepui) as sister to all other species. Based on phylogeny and geographic distribution, we identified 14 subclades as putative species within Chironius fuscus, C. multiventris (including C. foveatus and C. laurenti), C. monticola, and C. exoletus. Under current taxonomy, these species show nearly twice as much genetic diversity as other species of Chironius for ND4. Biogeographical analyses using BioGeoBEARS suggest that current distribution patterns of Chironius species across South America resulted from multiple range expansions. The MRCA of the clade C. challenger + C. grandisquamis was most likely distributed over the Pantepui region, the Andes, and the Chocoan Rainforest, whereas the remaining lineages probably evolved from an Amazonian ancestor.}, } @article {pmid30366085, year = {2019}, author = {Engelbrecht, HM and Branch, WR and Greenbaum, E and Alexander, GJ and Jackson, K and Burger, M and Conradie, W and Kusamba, C and Zassi-Boulou, AG and Tolley, KA}, title = {Diversifying into the branches: Species boundaries in African green and bush snakes, Philothamnus (Serpentes: Colubridae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {357-365}, doi = {10.1016/j.ympev.2018.10.023}, pmid = {30366085}, issn = {1095-9513}, abstract = {The African green and bush snakes of the genus Philothamnus currently comprises 21 species and three subspecies and occurs throughout sub-Saharan Africa. The genus has been the subject of previous taxonomic revisions based on traditional morphological characters and limited genetic assessment, and may not reflect their evolutionary history. Indeed, previous findings based on phylogenetics show discordant results of interspecific relationships and question the monophyly of the genus, although taxon sampling has been limited to date. We investigated phylogenetic affinities within Philothamnus with more inclusive genetic and geographical sampling, with the aim of better understanding their evolutionary history, so that future taxonomic revision of Philothamnus can be better informed. Species relationships were examined within a phylogenetic context and sampling included 133 ingroup samples from 16 taxa. Phylogenies were constructed in Bayesian and likelihood frameworks using three mitochondrial (16S, cyt b and ND4) and two nuclear (c-mos and RAG1) markers. Competing hypotheses relating to the monophyly of the genus were tested with a Shimodaira-Hasegawa test. To examine species boundaries, Bayesian General Mixed Yule-Coalescent Model and multi-rate Poisson Tree Processes analyses were conducted. In addition, a barcoding approach was used to further clarify species-level relationships by comparing frequency distributions between intra- and interspecific sequence divergence. The genus was recovered as monophyletic; however, species-delimitation results suggest that the current taxonomy does not reflect the evolutionary history of this group. For example, Philothamnus s. semivariegatus is paraphyletic, with at least four distinct clades. Philothamnus carinatus consists of two cryptic (sister) lineages from Central and West Africa that are deeply divergent, suggesting a long history of isolation between those regions. Furthermore, the subspecies P. n. natalensis and P. n. occidentalis show strong support for species-level divergence, which reflects their morphological and ecological differences. Accordingly, we elevate P. occidentalisnov. comb. to a full species. A fully informed taxonomic revision of these taxa will require additional morphological and ecological data for corroboration, but it seems that the morphological characters (e.g. scalation, dentition) used to describe these species to date are labile within and between species. This most likely has clouded our understanding of the species boundaries within the genus. Our phylogeny and species-delimitation analyses should provide a sounder framework for taxonomy, but may also prove useful toward understanding the morphological adaptations of these species to their respective habitats.}, } @article {pmid30365920, year = {2018}, author = {Ratcliffe, LE and Asiedu, EK and Pickett, CJ and Warburton, MA and Izzi, SA and Meedel, TH}, title = {The Ciona myogenic regulatory factor functions as a typical MRF but possesses a novel N-terminus that is essential for activity.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.10.010}, pmid = {30365920}, issn = {1095-564X}, support = {R15 HD047357/HD/NICHD NIH HHS/United States ; }, abstract = {Electroporation-based assays were used to test whether the myogenic regulatory factor (MRF) of Ciona intestinalis (CiMRF) interferes with endogenous developmental programs, and to evaluate the importance of its unusual N-terminus for muscle development. We found that CiMRF suppresses both notochord and endoderm development when it is expressed in these tissues by a mechanism that may involve activation of muscle-specific microRNAs. Because these results add to a large body of evidence demonstrating the exceptionally high degree of functional conservation among MRFs, we were surprised to discover that non-ascidian MRFs were not myogenic in Ciona unless they formed part of a chimeric protein containing the CiMRF N-terminus. Equally surprising, we found that despite their widely differing primary sequences, the N-termini of MRFs of other ascidian species could form chimeric MRFs that were also myogenic in Ciona. This domain did not rescue the activity of a Brachyury protein whose transcriptional activation domain had been deleted, and so does not appear to constitute such a domain. Our results indicate that ascidians have previously unrecognized and potentially novel requirements for MRF-directed myogenesis. Moreover, they provide the first example of a domain that is essential to the core function of an important family of gene regulatory proteins, one that, to date, has been found in only a single branch of the family.}, } @article {pmid30365879, year = {2018}, author = {}, title = {UK Biobank data on 500,000 people paves way to precision medicine.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {163-164}, doi = {10.1038/d41586-018-06950-9}, pmid = {30365879}, issn = {1476-4687}, mesh = {*Biological Specimen Banks ; Biomedical Research ; Genomics ; *Precision Medicine ; United Kingdom ; }, } @article {pmid30365878, year = {2018}, author = {}, title = {Brexit is already damaging European science.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {433-434}, doi = {10.1038/d41586-018-06826-y}, pmid = {30365878}, issn = {1476-4687}, } @article {pmid30364957, year = {2018}, author = {Lee, JM and Song, HJ and Park, SI and Lee, YM and Jeong, SY and Cho, TO and Kim, JH and Choi, HG and Choi, CG and Nelson, WA and Fredericq, S and Bhattacharya, D and Yoon, HS}, title = {Mitochondrial and Plastid Genomes from Coralline Red Algae Provide Insights into the Incongruent Evolutionary Histories of Organelles.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2961-2972}, pmid = {30364957}, issn = {1759-6653}, abstract = {Mitochondria and plastids are generally uniparentally inherited and have a conserved gene content over hundreds of millions of years, which makes them potentially useful phylogenetic markers. Organelle single gene-based trees have long been the basis for elucidating interspecies relationships that inform taxonomy. More recently, high-throughput genome sequencing has enabled the construction of massive organelle genome databases from diverse eukaryotes, and these have been used to infer species relationships in deep evolutionary time. Here, we test the idea that despite their expected utility, conflicting phylogenetic signal may exist in mitochondrial and plastid genomes from the anciently diverged coralline red algae (Rhodophyta). We generated complete organelle genome data from five coralline red algae (Lithothamnion sp., Neogoniolithon spectabile, Renouxia sp., Rhodogorgon sp., and Synarthrophyton chejuensis) for comparative analysis with existing organelle genome data from two other species (Calliarthron tuberculosum and Sporolithon durum). We find strong evidence for incongruent phylogenetic signal from both organelle genomes that may be explained by incomplete lineage sorting that has maintained anciently derived gene copies or other molecular evolutionary processes such as hybridization or gene flow during the evolutionary history of coralline red algae.}, } @article {pmid30364947, year = {2018}, author = {Hartasánchez, DA and Brasó-Vives, M and Heredia-Genestar, JM and Pybus, M and Navarro, A}, title = {Effect of Collapsed Duplications on Diversity Estimates: What to Expect.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2899-2905}, pmid = {30364947}, issn = {1759-6653}, abstract = {The study of segmental duplications (SDs) and copy-number variants (CNVs) is of great importance in the fields of genomics and evolution. However, SDs and CNVs are usually excluded from genome-wide scans for natural selection. Because of high identity between copies, SDs and CNVs that are not included in reference genomes are prone to be collapsed-that is, mistakenly aligned to the same region-when aligning sequence data from single individuals to the reference. Such collapsed duplications are additionally challenging because concerted evolution between duplications alters their site frequency spectrum and linkage disequilibrium patterns. To investigate the potential effect of collapsed duplications upon natural selection scans we obtained expectations for four summary statistics from simulations of duplications evolving under a range of interlocus gene conversion and crossover rates. We confirm that summary statistics traditionally used to detect the action of natural selection on DNA sequences cannot be applied to SDs and CNVs since in some cases values for known duplications mimic selective signatures. As a proof of concept of the pervasiveness of collapsed duplications, we analyzed data from the 1,000 Genomes Project. We find that, within regions identified as variable in copy number, diversity between individuals with the duplication is consistently higher than between individuals without the duplication. Furthermore, the frequency of single nucleotide variants (SNVs) deviating from Hardy-Weinberg Equilibrium is higher in individuals with the duplication, which strongly suggests that higher diversity is a consequence of collapsed duplications and incorrect evaluation of SNVs within these CNV regions.}, } @article {pmid30364940, year = {2018}, author = {Liu, X and Sun, Z and Dong, W and Wang, Z and Zhang, L}, title = {Expansion and Functional Divergence of the SHORT VEGETATIVE PHASE (SVP) Genes in Eudicots.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3026-3037}, pmid = {30364940}, issn = {1759-6653}, abstract = {SHORT VEGETATIVE PHASE (SVP) genes are members of the well-known MADS-box gene family that regulates vital developmental processes in plants. In Arabidopsis, there are two SVP paralogs, SVP/AGAMOUS-LIKE22 (SVP/AGL22) and AGL24. SVP protein suppresses the flowering process, whereas AGL24 acts as a flowering activator. Phylogenetic analysis of SVP genes representing most of the sequenced eudicot species showed that the SVP gene family could be divided into three major clades in eudicots (SVP1, SVP2, and SVP3), most likely resulting from an ancient whole-genome triplication in core eudicots. Among them, the SVP1 (SVP) and SVP2 (AGL24) clades are retained in nearly all species, whereas the SVP3 clade has been lost in Brassicaceae, Myrtaceae, and some species in other families. Reflecting lineage-specific tandem duplication and whole-genome duplication, SVP gene copy numbers ranged from 3 to 11 in the analyzed species. Sequence analysis showed that SVP3 proteins have obvious differences with SVP1 and SVP2 in the C-terminal (C) domain and intervening (I) domain. Positive selection analysis also showed that the ω (dN/dS) value was highest in the SVP3 clade, with 17 positive selection sites detected in the SVP3 clade. Promoter analysis for cis-regulatory elements showed that some genes in the SVP2 and SVP3 clades may be regulated by abscisic acid, ethylene, and gibberellin. RNA-seq data from grape, poplar, and apple revealed that genes in SVP3 group are highly expressed in vegetative organs such as buds, leaves, cotyledons, and dormant buds in particular, indicating the involvement of genes belong to SVP3 group in the dormancy process. Overall, the findings underscore the functional diversity of the SVP genes in eudicots.}, } @article {pmid30364489, year = {2018}, author = {Kim, B}, title = {How to Reveal Magnitude of Gene Signals: Hierarchical Hypergeometric Complementary Cumulative Distribution Function.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318797352}, pmid = {30364489}, issn = {1176-9343}, abstract = {This article introduces a new method for genome-wide association study (GWAS), hierarchical hypergeometric complementary cumulative distribution function (HH-CCDF). Existing GWAS methods, e.g. the linear model and hierarchical association coefficient algorithm, calculate the association between a marker variable and a phenotypic variable. The ideal GWAS practice is to calculate the association between a marker variable and a gene-signal variable. If the gene-signal variable and phenotypic variable are imperfectly proportional, the existing methods do not properly reveal the magnitude of the association between the gene-signal variable and marker variable. The HH-CCDF mitigates the impact of the imperfect proportionality between the phenotypic variable and gene-signal variable and thus better reveals the magnitude of gene signals. The HH-CCDF will provide new insights into GWAS approaches from the viewpoint of revealing the magnitude of gene signals.}, } @article {pmid30364468, year = {2018}, author = {Caetano-Anollés, G and Nasir, A and Kim, KM and Caetano-Anollés, D}, title = {Rooting Phylogenies and the Tree of Life While Minimizing Ad Hoc and Auxiliary Assumptions.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318805101}, pmid = {30364468}, issn = {1176-9343}, abstract = {Phylogenetic methods unearth evolutionary history when supported by three starting points of reason: (1) the continuity axiom begs the existence of a "model" of evolutionary change, (2) the singularity axiom defines the historical ground plan (phylogeny) in which biological entities (taxa) evolve, and (3) the memory axiom demands identification of biological attributes (characters) with historical information. Axiom consequences are interlinked, making the retrodiction enterprise an endeavor of reciprocal fulfillment. In particular, establishing direction of evolutionary change (character polarization) roots phylogenies and enables testing the existence of historical memory (homology). Unfortunately, rooting phylogenies, especially the "tree of life," generally follow narratives instead of integrating empirical and theoretical knowledge of retrodictive exploration. This stems mostly from a focus on molecular sequence analysis and uncertainties about rooting methods. Here, we review available rooting criteria, highlighting the need to minimize both ad hoc and auxiliary assumptions, especially argumentative ad hocness. We show that while the outgroup comparison method has been widely adopted, the generality criterion of nesting and additive phylogenetic change embodied in Weston rule offers the most powerful rooting approach. We also propose a change of focus, from phylogenies that describe the evolution of biological systems to those that describe the evolution of parts of those systems. This weakens violation of character independence, helps formalize the generality criterion of rooting, and provides new ways to study the problem of evolution.}, } @article {pmid30364450, year = {2018}, author = {Greenspan, NS}, title = {Autism, evolution, and the inadequacy of 'spectrum'.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {213-216}, pmid = {30364450}, issn = {2050-6201}, abstract = {Lay Summary: Individuals diagnosed with autism display variation in many traits, such as interest and ability in social interaction or resistance to change. Referring to this variation as a 'spectrum', defined as a range of values along an axis, understates the extent of such variation and can foster incorrect inferences. In psychiatry, the currently accepted term for a developmental disability characterized by variably impaired social and communicative skills, repetitive behaviors, and restricted interests is "autism spectrum disorder." "Spectrum," typically refers to values of a variable distributed along a single dimension, incorrectly suggesting people with autism can be simply ranked as more or less 'autistic.' In fact, there are multiple traits that pertain to autism and that can vary somewhat independently, in part due to the evolutionary mechanisms that give rise to risk alleles. Therefore, a new and more accurate clinical descriptor should be adopted. I propose: autism-related disorders (ARD).}, } @article {pmid30364335, year = {2018}, author = {Fitzpatrick, CL and Hobson, EA and Mendelson, TC and Rodríguez, RL and Safran, RJ and Scordato, ESC and Servedio, MR and Stern, CA and Symes, LB and Kopp, M}, title = {Theory Meets Empiry: A Citation Network Analysis.}, journal = {Bioscience}, volume = {68}, number = {10}, pages = {805-812}, pmid = {30364335}, issn = {0006-3568}, support = {T32 HD049336/HD/NICHD NIH HHS/United States ; }, abstract = {According to a recent survey, ecologists and evolutionary biologists feel that theoretical and empirical research should coexist in a tight feedback loop but believe that the two domains actually interact very little. We evaluate this perception using a citation network analysis for two data sets, representing the literature on sexual selection and speciation. Overall, 54%-60% of citations come from a paper's own category, whereas 17%-23% are citations across categories. These cross-citations tend to focus on highly cited papers, and we observe a positive correlation between the numbers of citations a study receives within and across categories. We find evidence that reviews can function as integrators between the two literatures, argue that theoretical models are analogous to specific empirical study systems, and complement our analyses by studying a cocitation network. We conclude that theoretical and empirical research are more tightly connected than generally thought but that avenues exist to further increase this integration.}, } @article {pmid30363817, year = {2018}, author = {Bolinska, A}, title = {Synthetic versus analytic approaches to protein and DNA structure determination.}, journal = {Biology & philosophy}, volume = {33}, number = {3}, pages = {26}, pmid = {30363817}, issn = {0169-3867}, abstract = {The structures of protein and DNA were discovered primarily by means of synthesizing component-level information about bond types, lengths, and angles, rather than analyzing X-ray diffraction photographs of these molecules. In this paper, I consider the synthetic and analytic approaches to exemplify alternative heuristics for approaching mid-twentieth-century macromolecular structure determination. I argue that the former was, all else being equal, likeliest to generate the correct structure in the shortest period of time. I begin by characterizing problem solving in these cases as proceeding via the elimination of candidate structures through the successive application of component-level information and interpretations of X-ray diffraction photographs, each of which serves as a kind of constraint on structure. Then, I argue that although each kind of constraint enables the elimination of a considerable proportion of candidate structures, component-level constraints are significantly more likely to do so correctly. Thus, considering them before X-ray diffraction photographs is a better heuristic than one that reverses this order. Because the synthetic approach that resulted in the determination of the protein and DNA structures exemplifies such a heuristic, its use can help account for these discoveries.}, } @article {pmid30362938, year = {2018}, author = {Sun, L and Liu, H and Chen, W and Huang, K and Lyu, W and Gao, X}, title = {Alsobacter soli sp. nov., a novel bacterium isolated from paddy soil, emended description of the genus Alsobacter and description of the family Alsobacteraceae fam. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3902-3907}, doi = {10.1099/ijsem.0.003088}, pmid = {30362938}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Oryza ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {Strain SH9T, an aerobic bacterium isolated from a paddy soil sample collected in Shanghai, China, was characterized using a polyphasic approach. It grew optimally at pH 7.0, temperatures of 30-35 °C and in the presence of 1 % (w/v) NaCl. Comparative analysis of 16S rRNA gene sequences showed that strain SH9T fell within the genus Alsobacter, forming a clear cluster with the type strain of Alsobacter metallidurans, with which it exhibited a 16S rRNA gene sequence similarity value of 98.5 %. Cells of strain SH9T were Gram-stain-negative, motile, non-spore-forming, rod-shaped, positive for catalase and oxidase activity, and negative for atmospheric nitrogen fixation and nitrate reduction. The strain was a chemo-organotrophic bacterium, incapable of growth on C1 substrates. The chemotaxonomic properties of strain SH9T were consistent with those of the genus Alsobacter: the predominant ubiquinone was Q-10, and the major fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and phosphatidylmonomethylethanolamine. The DNA G+C content was 68.5 mol%. Strain SH9T exhibited a DNA-DNA relatedness level of 20±2 % with A. metallidurans NBRC 107718T. Based on the data obtained, strain SH9T represents a novel species of the genus Alsobacter, for which the name Alsobactersoli sp. nov. is proposed. The type strain is SH9T (=JCM 32501T=CCTCC AB 2017284T). A new family, Alsobacteraceae fam. nov., is also proposed encompassing strain SH9T and Alsobacter metallidurans NBRC 107718T.}, } @article {pmid30362936, year = {2018}, author = {Li, YR and Zhu, ZN and Li, YQ and Xiao, M and Han, MX and Wadaan, MAM and Hozzein, WN and An, DD and Li, WJ}, title = {Microbacterium halophytorum sp. nov., a novel endophytic actinobacterium isolated from halophytes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3928-3934}, doi = {10.1099/ijsem.0.003092}, pmid = {30362936}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Endophytes/classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salt-Tolerant Plants/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {Two actinobacterial strains, YJYP 303T and YZYP 518, were isolated from two species of halophytes collected from the southern edge of the Gurbantunggut Desert. Cells were Gram-stain-positive, aerobic, short rods and without flagella. Growth of the two strains was found to occur at 4-44 °C, pH 6.0-12.0 and in the presence of up to 15 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the two strains are associated with members of the genus Microbacterium. In the phylogenetic tree, the two strains shared a clade with Microbacterium halotolerans YIM 70130T (97.58 % 16S rRNA gene sequence identity) and Microbacterium populi KCTC 29152T (96.54 %). The average nucleotide identity values of strain YJYP 303T and YZYP 518 to M. halotolerans YIM 70130T were determined to be 79.97 and 80.03 %, respectively. The genomic DNA G+C contents of strains YJYP 303T and YZYP 518 were 69.72 and 70.57 %, respectively. The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The predominant respiratory quinones was MK-11, followed by MK-10 and MK-12. The muramic acid type of peptidoglycan was N-glycolyl. The whole-cell sugars were mannose, ribose, rhamnose, glucose, galactose and two unidentified sugars. The cell-wall amino acids were glutamic acid, ornithine, glycine and alanine. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unidentified glycolipid. On the basis of the evidence presented in this study, strains YJYP 303T and YZYP 518 are characterized as members of a novel species in the genus Microbacterium, for which the name Microbacteriumhalophytorum sp. nov. is proposed. The type strain is YJYP 303T (=CGMCC 1.16264T=KCTC 49100T).}, } @article {pmid30362935, year = {2018}, author = {Cao, J and Lai, Q and Liu, P and Wei, Y and Wang, L and Liu, R and Fang, J}, title = {Salinimonas sediminis sp. nov., a piezophilic bacterium isolated from a deep-sea sediment sample from the New Britain Trench.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3766-3771}, doi = {10.1099/ijsem.0.003055}, pmid = {30362935}, issn = {1466-5034}, mesh = {Alteromonadaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cold Temperature ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Geologic Sediments/*microbiology ; Pacific Ocean ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A cold-adapted, piezophilic, slightly halophilic bacterium, designated as N102T, was isolated from a deep-sea (4700 m) sediment sample collected from the New Britain Trench. Strain N102T was Gram-stain-negative, rod-shaped, oxidase- and catalase-positive, and grew optimally at 28 °C (range, 4-40 °C), pH 7.0-7.5 (range, 6.0-9.0) and 3-4 %(w/v) NaCl (range, 2-15 %). The optimum pressure for growth was 10 MPa with tolerance up to 70 MPa. 16S rRNA gene sequence analysis showed that strain N102T was most closely related to Alteromonas addita R10SW13T (97.2 %), Alteromonas stellipolaris LMG 21861T (97.1 %), Alteromonas gracilis 9a2T (97.1 %), Salinimonas lutimaris DPSR-4T (96.1 %) and Salinimonas chungwhensis BH030046T (95.4 %). Phylogenetic analyses based on 16S rRNA gene, gyrB gene and whole-genome sequences placed strain N102T within the genus Salinimonas. Genomic comparisons based on average nucleotide identity and tetranucleotide signature frequencies corroborated the results of the phylogenetic analyses. The principal fatty acids were summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), C16 : 0 and summed feature 8 (C18 : 1ω7c/C18 : 1ω6c). The major respiratory quinone was ubiquinone 8. The predominant polar lipids were phosphatidylethanolamine, phosphatidylglycerol and an unidentified phospholipid. The G+C content of the genomic DNA was 48.2 mol%. On the basis of phenotypic, chemotaxonomic and molecular data, we conclude that strain N102T represents a novel species of the genus Salinimonas, for which the name Salinimonassediminis sp. nov. is proposed (type strain N102T=MCCC 1K03497T=KCTC 62440T).}, } @article {pmid30362934, year = {2018}, author = {Wang, X and Yang, J and Lu, S and Lai, XH and Jin, D and Pu, J and Zhang, G and Huang, Y and Zhu, W and Wu, X and Liang, H and Xu, J}, title = {Nocardioides houyundeii sp. nov., isolated from Tibetan antelope faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3874-3880}, doi = {10.1099/ijsem.0.003076}, pmid = {30362934}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Animals ; Antelopes/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Feces/*microbiology ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sheep ; Tibet ; }, abstract = {In the present study, we describe two novel Gram-stain-positive, irregular rod-shaped bacterial strains, 78T and 601, that had been isolated from the faeces of Tibetan antelopes at the Hoh Xil Nature Reserve, Qinghai-Tibet Plateau, China. The cells were aerobic, oxidase-negative and catalase-positive. When cultured on brain-heart infusion agar supplemented with 5 % sheep blood, colonies were cream in colour, circular, smooth and convex. Phylogenetic analysis based on the full-length 16S rRNA sequences revealed that type strain 78T and strain 601 belong to the genus Nocardioides, sharing the highest similarity to Nocardioides solisilvae JCM 31492T (98.3 %), Nocardioides gilvus XZ17T (97.4 %) and Nocardioides daejeonensis JCM 16922T (97.4 %). The average nucleotide identity values between the two novel strains and the three closely related type strains of the genus Nocardioides were lower than the 95-96 % threshold. The DNA G+C content of strains 78T and 601 were 71.2 and 71.3 mol% respectively. MK-8 (H4) was the predominant respiratory quinone and ll-2,6-diaminopimelic acid was the diagnostic diamino acid in its cell-wall peptidoglycan. Its polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, an unidentified phospholipid and an unidentified lipid. The main whole-cell sugars were rhamnose, xylose and galactose and the major fatty acids (>10 %) were C17 : 1ω8c, iso-C16 : 0 and C18 : 1ω9c. These data supported the affiliation of strains 78T and 601 to genus Nocardioides. Based on evidence collected from the phenotypic, genotypic and phylogenetic analyses, we propose a novel species named Nocardioideshouyundeii sp. nov. The type strain is 78T (=CGMCC 4.7461T=DSM 106424T).}, } @article {pmid30362527, year = {2018}, author = {}, title = {.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2272}, doi = {10.1111/evo.13568}, pmid = {30362527}, issn = {1558-5646}, } @article {pmid30362526, year = {2018}, author = {}, title = {EDITORIAL COMMENT.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2267}, doi = {10.1111/evo.13605}, pmid = {30362526}, issn = {1558-5646}, } @article {pmid30362300, year = {2019}, author = {Akkaya, Ö and Nikel, PI and Pérez-Pantoja, D and de Lorenzo, V}, title = {Evolving metabolism of 2,4-dinitrotoluene triggers SOS-independent diversification of host cells.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {314-326}, doi = {10.1111/1462-2920.14459}, pmid = {30362300}, issn = {1462-2920}, support = {//Danish Council for Independent Research/ ; //Novo Nordisk Foundation/ ; H2020-FET-OPEN-RIA-2017-1-766975//Ministry of Economy and Competitiveness/ ; EUH2020-BIOTEC-2014-2015-6335536//Ministry of Economy and Competitiveness/ ; }, abstract = {The molecular mechanisms behind the mutagenic effect of reactive oxygen species (ROS) released by defective metabolization of xenobiotic 2,4-dinitrotoluene (DNT) by a still-evolving degradation pathway were studied. To this end, the genes required for biodegradation of DNT from Burkholderia cepacia R34 were implanted in Escherichia coli and the effect of catabolizing the nitroaromatic compound monitored with stress-related markers and reporters. Such a proxy of the naturally-occurring scenario faithfully recreated the known accumulation of ROS caused by faulty metabolism of DNT and the ensuing onset of an intense mutagenesis regime. While ROS triggered an oxidative stress response, neither homologous recombination was stimulated nor the recA promoter activity increased during DNT catabolism. Analysis of single-nucleotide changes occurring in rpoB during DNT degradation suggested a relaxation of DNA replication fidelity rather than direct damage to DNA. Mutants frequencies were determined in strains defective in either converting DNA damage into mutagenesis or mediating inhibition of mismatch repair through a general stress response. The results revealed that the mutagenic effect of ROS was largely SOS-independent and stemmed instead from stress-induced changes of rpoS functionality. Evolution of novel metabolic properties thus resembles the way sublethal antibiotic concentrations stimulate the appearance of novel resistance genes.}, } @article {pmid30362296, year = {2019}, author = {Laverde Gomez, JA and Mukhopadhya, I and Duncan, SH and Louis, P and Shaw, S and Collie-Duguid, E and Crost, E and Juge, N and Flint, HJ}, title = {Formate cross-feeding and cooperative metabolic interactions revealed by transcriptomics in co-cultures of acetogenic and amylolytic human colonic bacteria.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {259-271}, doi = {10.1111/1462-2920.14454}, pmid = {30362296}, issn = {1462-2920}, support = {BB/L009951/1//BBSRC/ ; }, abstract = {Interspecies cross-feeding is a fundamental factor in anaerobic microbial communities. In the human colon, formate is produced by many bacterial species but is normally detected only at low concentrations. Ruminococcus bromii produces formate, ethanol and acetate in approximately equal molar proportions in pure culture on RUM-RS medium with 0.2% Novelose resistant starch (RS3) as energy source. Batch co-culturing on starch with the acetogen Blautia hydrogenotrophica however led to the disappearance of formate and increased levels of acetate, which is proposed to occur through the routing of formate via the Wood Ljungdahl pathway of B. hydrogenotrophica. We investigated these inter-species interactions further using RNAseq to examine gene expression in continuous co-cultures of R. bromii and B. hydrogenotrophica. Transcriptome analysis revealed upregulation of B. hydrogenotrophica genes involved in the Wood-Ljungdahl pathway and of a 10 gene cluster responsible for increased branched chain amino acid fermentation in the co-cultures. Cross-feeding between formate-producing species and acetogens may be a significant factor in short chain fatty acid formation in the colon contributing to high rates of acetate production. Transcriptome analysis also indicated competition for the vitamin thiamine and downregulation of dissimilatory sulfate reduction and key redox proteins in R. bromii in the co-cultures, thus demonstrating the wide-ranging consequences of inter-species interactions in this model system.}, } @article {pmid30362272, year = {2019}, author = {Liao, L and Liu, C and Zeng, Y and Zhao, B and Zhang, J and Chen, B}, title = {Multipartite genomes and the sRNome in response to temperature stress of an Arctic Pseudoalteromonas fuliginea BSW20308.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {272-285}, doi = {10.1111/1462-2920.14455}, pmid = {30362272}, issn = {1462-2920}, support = {CHINARE02-01CHINARE04-03//Chinese Polar Environment Comprehensive Investigation and Assessment Program/ ; 2018YFC14067012018YFC1406702//National Key Research and Development Plan of China/ ; 4140618141476171//National Natural Science Foundation of China/ ; }, abstract = {Little is known about the survival and effect of rapid climate warming on Pseudoalteromonas in the Arctic, although it is abundant and important in this ecosystem. Here, we investigated a cold-adapted Pseudoalteromonas fuliginea BSW20308 from the Arctic Ocean, from the genome to its transcriptomic responses towards temperature changes. It contained two circular chromosomes, with the second chromosome probably evolved from an ancestral plasmid. The evolution of multipartite genomes may be advantageous for its survival under changing environments. RNA-seq analysis revealed the extensive involvement of sRNome in response to temperature stress for the first time, especially tmRNA and a novel Pf1 sRNA strongly induced under heat stress. The present study makes significant contributions towards the understanding of Pseudoalteromonas in two aspects: the genome structure and evolution of its two chromosomes, and the important discovery of the sRNome in response to temperature stress.}, } @article {pmid30362214, year = {2019}, author = {Götz, F and Pjevac, P and Markert, S and McNichol, J and Becher, D and Schweder, T and Mussmann, M and Sievert, SM}, title = {Transcriptomic and proteomic insight into the mechanism of cyclooctasulfur- versus thiosulfate-oxidation by the chemolithoautotroph Sulfurimonas denitrificans.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {244-258}, doi = {10.1111/1462-2920.14452}, pmid = {30362214}, issn = {1462-2920}, support = {OCE-1559198//NSF/ ; //The Investment in Science Fund at WHOI/ ; //Institute of Marine Biotechnology e.V./ ; }, abstract = {Chemoautotrophic bacteria belonging to the genus Sulfurimonas (class Campylobacteria) were previously identified as key players in the turnover of zero-valence sulfur, a central intermediate in the marine sulfur cycle. S. denitrificans was further shown to be able to oxidize cyclooctasulfur (S8). However, at present the mechanism of activation and metabolism of cyclooctasulfur is not known. Here, we assessed the transcriptome and proteome of S. denitrificans grown with either thiosulfate or S8 as the electron donor. While the overall expression profiles under the two growth conditions were rather similar, distinct differences were observed that could be attributed to the utilization of S8 . This included a higher abundance of expressed genes related to surface attachment in the presence of S8 , and the differential regulation of the sulfur-oxidation multienzyme complex (SOX), which in S. denitrificans is encoded in two gene clusters: soxABXY 1 Z 1 and soxCDY 2 Z 2 . While the proteins of both clusters were present with thiosulfate, only proteins of the soxCDY 2 Z 2 were detected at significant levels with S8 . Based on these findings a model for the oxidation of S8 is proposed. Our results have implications for interpreting metatranscriptomic and -proteomic data and for the observed high level of diversification of soxY 2 Z 2 among sulfur-oxidizing Campylobacteria.}, } @article {pmid30361843, year = {2019}, author = {Newase, S and Kapadnis, BP and Shashidhar, R}, title = {Isolation and Genome Sequence Characterization of Bacteriophage vB_SalM_PM10, a Cba120virus, Concurrently Infecting Salmonella enterica Serovars Typhimurium, Typhi, and Enteritidis.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {86-94}, doi = {10.1007/s00284-018-1588-8}, pmid = {30361843}, issn = {1432-0991}, support = {No.F.6-6/2017-18/EMERITUS-2017-18-GEN-9819/(SA-II)//University Grants Commission (IN)/ ; GOI-E-156//Department of Atomic Energy, Government of India/ ; }, abstract = {The prevalence of multidrug-resistant Salmonella is ever increasing and calls for alternatives to antibiotics. The use of phages has been anticipated to reduce the multidrug-resistant human pathogens in food environment. Salmonella phage vB_SalM_PM10 (PM10) was isolated from sewage-polluted river in India. It shows an icosahedral head (94 ± 4 nm) along with a long contractile tail (106 ± 7 × 18 ± 2 nm), a morphotype of family Ackermannviridae. Additionally, the phage displayed the features resembling to existing Cba120viruses. Phage PM10 could infect S. enterica serovars Typhimurium, Typhi, and Enteritidis. The genome sequencing analysis of phage PM10 revealed circular 158.08 kb double-stranded DNA, with the GC content of 44.6%. Two hundred and nine ORFs, 171 putative promoters, 122 rho-independent terminators, and 5 transfer RNA encoding genes were found in the genome. The genome-wide comparisons and phylogenetic analyses showed that phage PM10 is closely related to Salmonella phage PhiSH19. Comparison of the tail-spike protein sequences encoded in PM10 and PhiSH19 genome showed the variation, which might have facilitated PM10's simultaneous infectivity to aforementioned S. enterica serovars. This is a varied host range than that of PhiSH19 or any other Cba120viruses.}, } @article {pmid30361751, year = {2018}, author = {Di Giulio, M}, title = {A Non-neutral Origin for Error Minimization in the Origin of the Genetic Code.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {593-597}, pmid = {30361751}, issn = {1432-1432}, abstract = {Massey (J Mol Evol 67:510-516, 2008; J Theor Biol 408:237-242, 2016; Nat Comput. https://doi.org/10.1007/s11047-017-9669-3, 2018) claims that the error minimization of the genetic code is derived by means of a neutral process and was not due to the action of natural selection. Here, I argue that this neutralist hypothesis of the origin of error minimization is not based directly on any neutral process but it could be only indirectly. On the contrary, it has been natural selection that has acted during the origin of the genetic code determining the property that similar amino acids are coded by similar codons within the genetic code table.}, } @article {pmid30361388, year = {2018}, author = {Budin, I and de Rond, T and Chen, Y and Chan, LJG and Petzold, CJ and Keasling, JD}, title = {Viscous control of cellular respiration by membrane lipid composition.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6419}, pages = {1186-1189}, doi = {10.1126/science.aat7925}, pmid = {30361388}, issn = {1095-9203}, abstract = {Lipid composition determines the physical properties of biological membranes and can vary substantially between and within organisms. We describe a specific role for the viscosity of energy-transducing membranes in cellular respiration. Engineering of fatty acid biosynthesis in Escherichia coli allowed us to titrate inner membrane viscosity across a 10-fold range by controlling the abundance of unsaturated or branched lipids. These fluidizing lipids tightly controlled respiratory metabolism, an effect that can be explained with a quantitative model of the electron transport chain (ETC) that features diffusion-coupled reactions between enzymes and electron carriers (quinones). Lipid unsaturation also modulated mitochondrial respiration in engineered budding yeast strains. Thus, diffusion in the ETC may serve as an evolutionary constraint for lipid composition in respiratory membranes.}, } @article {pmid30361387, year = {2018}, author = {Liénart, S and Merceron, R and Vanderaa, C and Lambert, F and Colau, D and Stockis, J and van der Woning, B and De Haard, H and Saunders, M and Coulie, PG and Savvides, SN and Lucas, S}, title = {Structural basis of latent TGF-β1 presentation and activation by GARP on human regulatory T cells.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {952-956}, doi = {10.1126/science.aau2909}, pmid = {30361387}, issn = {1095-9203}, abstract = {Transforming growth factor-β1 (TGF-β1) is one of very few cytokines produced in a latent form, requiring activation to exert any of its vastly diverse effects on development, immunity, and cancer. Regulatory T cells (Tregs) suppress immune cells within close proximity by activating latent TGF-β1 presented by GARP (glycoprotein A repetitions predominant) to integrin αVβ8 on their surface. We solved the crystal structure of GARP:latent TGF-β1 bound to an antibody that stabilizes the complex and blocks release of active TGF-β1. This finding reveals how GARP exploits an unusual medley of interactions, including fold complementation by the amino terminus of TGF-β1, to chaperone and orient the cytokine for binding and activation by αVβ8. Thus, this work further elucidates the mechanism of antibody-mediated blockade of TGF-β1 activation and immunosuppression by Tregs.}, } @article {pmid30361386, year = {2018}, author = {Gong, H and Li, J and Xu, A and Tang, Y and Ji, W and Gao, R and Wang, S and Yu, L and Tian, C and Li, J and Yen, HY and Man Lam, S and Shui, G and Yang, X and Sun, Y and Li, X and Jia, M and Yang, C and Jiang, B and Lou, Z and Robinson, CV and Wong, LL and Guddat, LW and Sun, F and Wang, Q and Rao, Z}, title = {An electron transfer path connects subunits of a mycobacterial respiratory supercomplex.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {}, doi = {10.1126/science.aat8923}, pmid = {30361386}, issn = {1095-9203}, abstract = {We report a 3.5-angstrom-resolution cryo-electron microscopy structure of a respiratory supercomplex isolated from Mycobacterium smegmatis. It comprises a complex III dimer flanked on either side by individual complex IV subunits. Complex III and IV associate so that electrons can be transferred from quinol in complex III to the oxygen reduction center in complex IV by way of a bridging cytochrome subunit. We observed a superoxide dismutase-like subunit at the periplasmic face, which may be responsible for detoxification of superoxide formed by complex III. The structure reveals features of an established drug target and provides a foundation for the development of treatments for human tuberculosis.}, } @article {pmid30361385, year = {2018}, author = {Sajadi, E and Palomaki, T and Fei, Z and Zhao, W and Bement, P and Olsen, C and Luescher, S and Xu, X and Folk, JA and Cobden, DH}, title = {Gate-induced superconductivity in a monolayer topological insulator.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {922-925}, doi = {10.1126/science.aar4426}, pmid = {30361385}, issn = {1095-9203}, abstract = {The layered semimetal tungsten ditelluride (WTe2) has recently been found to be a two-dimensional topological insulator (2D TI) when thinned down to a single monolayer, with conducting helical edge channels. We found that intrinsic superconductivity can be induced in this monolayer 2D TI by mild electrostatic doping at temperatures below 1 kelvin. The 2D TI-superconductor transition can be driven by applying a small gate voltage. This discovery offers possibilities for gate-controlled devices combining superconductivity and nontrivial topological properties, and could provide a basis for quantum information schemes based on topological protection.}, } @article {pmid30361384, year = {2018}, author = {Fatemi, V and Wu, S and Cao, Y and Bretheau, L and Gibson, QD and Watanabe, K and Taniguchi, T and Cava, RJ and Jarillo-Herrero, P}, title = {Electrically tunable low-density superconductivity in a monolayer topological insulator.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {926-929}, doi = {10.1126/science.aar4642}, pmid = {30361384}, issn = {1095-9203}, abstract = {Turning on superconductivity in a topologically nontrivial insulator may provide a route to search for non-Abelian topological states. However, existing demonstrations of superconductor-insulator switches have involved only topologically trivial systems. Here we report reversible, in situ electrostatic on-off switching of superconductivity in the recently established quantum spin Hall insulator monolayer tungsten ditelluride (WTe2). Fabricated into a van der Waals field-effect transistor, the monolayer's ground state can be continuously gate-tuned from the topological insulating to the superconducting state, with critical temperatures Tc up to ~1 kelvin. Our results establish monolayer WTe2 as a material platform for engineering nanodevices that combine superconducting and topological phases of matter.}, } @article {pmid30361383, year = {2018}, author = {Orning, P and Weng, D and Starheim, K and Ratner, D and Best, Z and Lee, B and Brooks, A and Xia, S and Wu, H and Kelliher, MA and Berger, SB and Gough, PJ and Bertin, J and Proulx, MM and Goguen, JD and Kayagaki, N and Fitzgerald, KA and Lien, E}, title = {Pathogen blockade of TAK1 triggers caspase-8-dependent cleavage of gasdermin D and cell death.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1064-1069}, doi = {10.1126/science.aau2818}, pmid = {30361383}, issn = {1095-9203}, support = {T32 AI007538/AI/NIAID NIH HHS/United States ; F30 AI129237/AI/NIAID NIH HHS/United States ; R01 AI067497/AI/NIAID NIH HHS/United States ; R01 AI083713/AI/NIAID NIH HHS/United States ; T32 AI095213/AI/NIAID NIH HHS/United States ; R01 AI139914/AI/NIAID NIH HHS/United States ; R01 AI075118/AI/NIAID NIH HHS/United States ; R25 HL092610/HL/NHLBI NIH HHS/United States ; }, abstract = {Limited proteolysis of gasdermin D (GSDMD) generates an N-terminal pore-forming fragment that controls pyroptosis in macrophages. GSDMD is processed via inflammasome-activated caspase-1 or -11. It is currently unknown whether macrophage GSDMD can be processed by other mechanisms. Here, we describe an additional pathway controlling GSDMD processing. The inhibition of TAK1 or IκB kinase (IKK) by the Yersinia effector protein YopJ elicits RIPK1- and caspase-8-dependent cleavage of GSDMD, which subsequently results in cell death. GSDMD processing also contributes to the NLRP3 inflammasome-dependent release of interleukin-1β (IL-1β). Thus, caspase-8 acts as a regulator of GSDMD-driven cell death. Furthermore, this study establishes the importance of TAK1 and IKK activity in the control of GSDMD cleavage and cytotoxicity.}, } @article {pmid30361376, year = {2018}, author = {Nielsen, KB}, title = {Putting my grad school angst to use.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {494}, doi = {10.1126/science.362.6413.494}, pmid = {30361376}, issn = {1095-9203}, } @article {pmid30361375, year = {2018}, author = {Zeng, WZ and Marshall, KL and Min, S and Daou, I and Chapleau, MW and Abboud, FM and Liberles, SD and Patapoutian, A}, title = {PIEZOs mediate neuronal sensing of blood pressure and the baroreceptor reflex.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {464-467}, doi = {10.1126/science.aau6324}, pmid = {30361375}, issn = {1095-9203}, support = {R01 DE022358/DE/NIDCR NIH HHS/United States ; R35 NS105067/NS/NINDS NIH HHS/United States ; DP1 AT009497/AT/NCCIH NIH HHS/United States ; OT2 OD023848/OD/NIH HHS/United States ; P01 HL014388/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Baroreflex/genetics/*physiology ; Blood Pressure/*physiology ; Ion Channels/genetics/*physiology ; Mechanotransduction, Cellular/genetics/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Neurons/*physiology ; Nodose Ganglion/physiology ; Optogenetics ; Pressoreceptors/*physiology ; }, abstract = {Activation of stretch-sensitive baroreceptor neurons exerts acute control over heart rate and blood pressure. Although this homeostatic baroreflex has been described for more than 80 years, the molecular identity of baroreceptor mechanosensitivity remains unknown. We discovered that mechanically activated ion channels PIEZO1 and PIEZO2 are together required for baroreception. Genetic ablation of both Piezo1 and Piezo2 in the nodose and petrosal sensory ganglia of mice abolished drug-induced baroreflex and aortic depressor nerve activity. Awake, behaving animals that lack Piezos had labile hypertension and increased blood pressure variability, consistent with phenotypes in baroreceptor-denervated animals and humans with baroreflex failure. Optogenetic activation of Piezo2-positive sensory afferents was sufficient to initiate baroreflex in mice. These findings suggest that PIEZO1 and PIEZO2 are the long-sought baroreceptor mechanosensors critical for acute blood pressure control.}, } @article {pmid30361374, year = {2018}, author = {Sallan, L and Friedman, M and Sansom, RS and Bird, CM and Sansom, IJ}, title = {The nearshore cradle of early vertebrate diversification.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {460-464}, doi = {10.1126/science.aar3689}, pmid = {30361374}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; Datasets as Topic ; Fishes/anatomy & histology/*classification ; *Fossils ; Fresh Water ; Jaw/anatomy & histology ; Phylogeny ; }, abstract = {Ancestral vertebrate habitats are subject to controversy and obscured by limited, often contradictory paleontological data. We assembled fossil vertebrate occurrence and habitat datasets spanning the middle Paleozoic (480 million to 360 million years ago) and found that early vertebrate clades, both jawed and jawless, originated in restricted, shallow intertidal-subtidal environments. Nearshore divergences gave rise to body plans with different dispersal abilities: Robust fishes shifted shoreward, whereas gracile groups moved seaward. Fresh waters were invaded repeatedly, but movement to deeper waters was contingent upon form and short-lived until the later Devonian. Our results contrast with the onshore-offshore trends, reef-centered diversification, and mid-shelf clustering observed for benthic invertebrates. Nearshore origins for vertebrates may be linked to the demands of their mobility and may have influenced the structure of their early fossil record and diversification.}, } @article {pmid30361373, year = {2018}, author = {Kratochwil, CF and Liang, Y and Gerwin, J and Woltering, JM and Urban, S and Henning, F and Machado-Schiaffino, G and Hulsey, CD and Meyer, A}, title = {Agouti-related peptide 2 facilitates convergent evolution of stripe patterns across cichlid fish radiations.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {457-460}, doi = {10.1126/science.aao6809}, pmid = {30361373}, issn = {1095-9203}, mesh = {Agouti-Related Protein/genetics/*physiology ; Animals ; *Biological Evolution ; CRISPR-Cas Systems ; Chromosome Mapping ; Cichlids/*anatomy & histology/genetics/*physiology ; Gene Knockout Techniques ; Genetic Loci ; Mutation ; *Skin Pigmentation/genetics ; }, abstract = {The color patterns of African cichlid fishes provide notable examples of phenotypic convergence. Across the more than 1200 East African rift lake species, melanic horizontal stripes have evolved numerous times. We discovered that regulatory changes of the gene agouti-related peptide 2 (agrp2) act as molecular switches controlling this evolutionarily labile phenotype. Reduced agrp2 expression is convergently associated with the presence of stripe patterns across species flocks. However, cis-regulatory mutations are not predictive of stripes across radiations, suggesting independent regulatory mechanisms. Genetic mapping confirms the link between the agrp2 locus and stripe patterns. The crucial role of agrp2 is further supported by a CRISPR-Cas9 knockout that reconstitutes stripes in a nonstriped cichlid. Thus, we unveil how a single gene affects the convergent evolution of a complex color pattern.}, } @article {pmid30361372, year = {2018}, author = {Moeller, AH and Suzuki, TA and Phifer-Rixey, M and Nachman, MW}, title = {Transmission modes of the mammalian gut microbiota.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {453-457}, doi = {10.1126/science.aat7164}, pmid = {30361372}, issn = {1095-9203}, support = {R01 GM074245/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacteria/classification/pathogenicity ; *Bacterial Physiological Phenomena ; Gastrointestinal Microbiome/*physiology ; Mice ; Mice, Inbred Strains ; }, abstract = {Mammals house a diversity of bacteria that affect health in various ways, but the routes by which bacterial lineages are transmitted between hosts remain poorly understood. We experimentally determined microbiota transmission modes by deriving 17 inbred mouse lines from two wild populations and monitoring their gut microbiotas for up to 11 host generations. Individual- and population-level microbiota compositions were maintained within mouse lines throughout the experiment, indicating predominantly vertical inheritance of the microbiota. However, certain bacterial taxa tended to be exchanged horizontally between mouse lines. Consistent with evolutionary theory, the degree of horizontal transmission predicted bacterial genera with pathogenic representatives responsible for human infections and hospitalizations.}, } @article {pmid30361371, year = {2018}, author = {Ripka, F and Kübler, H and Löw, R and Pfau, T}, title = {A room-temperature single-photon source based on strongly interacting Rydberg atoms.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {446-449}, doi = {10.1126/science.aau1949}, pmid = {30361371}, issn = {1095-9203}, abstract = {Tailored quantum states of light can be created via a transfer of collective quantum states of matter to light modes. Such collective quantum states emerge in interacting many-body systems if thermal fluctuations are overcome by sufficient interaction strengths. Therefore, ultracold temperatures or strong confinement are typically required. We show that the exaggerated interactions between Rydberg atoms allow for collective quantum states even above room temperature. The emerging Rydberg interactions lead both to suppression of multiple Rydberg state excitations and destructive interference due to polariton dephasing. We experimentally implemented a four-wave mixing scheme to demonstrate an on-demand single-photon source. The combination of glass cell technology, identical atoms, and operation around room temperature promises scalability and integrability. This approach has the potential for various applications in quantum information processing and communication.}, } @article {pmid30361370, year = {2018}, author = {Li, L and Lin, RB and Krishna, R and Li, H and Xiang, S and Wu, H and Li, J and Zhou, W and Chen, B}, title = {Ethane/ethylene separation in a metal-organic framework with iron-peroxo sites.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {443-446}, doi = {10.1126/science.aat0586}, pmid = {30361370}, issn = {1095-9203}, abstract = {The separation of ethane from its corresponding ethylene is an important, challenging, and energy-intensive process in the chemical industry. Here we report a microporous metal-organic framework, iron(III) peroxide 2,5-dioxido-1,4-benzenedicarboxylate [Fe2(O2)(dobdc) (dobdc4-: 2,5-dioxido-1,4-benzenedicarboxylate)], with iron (Fe)-peroxo sites for the preferential binding of ethane over ethylene and thus highly selective separation of C2H6/C2H4 Neutron powder diffraction studies and theoretical calculations demonstrate the key role of Fe-peroxo sites for the recognition of ethane. The high performance of Fe2(O2)(dobdc) for the ethane/ethylene separation has been validated by gas sorption isotherms, ideal adsorbed solution theory calculations, and simulated and experimental breakthrough curves. Through a fixed-bed column packed with this porous material, polymer-grade ethylene (99.99% pure) can be straightforwardly produced from ethane/ethylene mixtures during the first adsorption cycle, demonstrating the potential of Fe2(O2)(dobdc) for this important industrial separation with a low energy cost under ambient conditions.}, } @article {pmid30361369, year = {2018}, author = {Henstridge, M and Pfeiffer, C and Wang, D and Boltasseva, A and Shalaev, VM and Grbic, A and Merlin, R}, title = {Synchrotron radiation from an accelerating light pulse.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {439-442}, doi = {10.1126/science.aat5915}, pmid = {30361369}, issn = {1095-9203}, abstract = {Synchrotron radiation-namely, electromagnetic radiation produced by charges moving in a curved path-is regularly generated at large-scale facilities where giga-electron volt electrons move along kilometer-long circular paths. We use a metasurface to bend light and demonstrate synchrotron radiation produced by a subpicosecond pulse, which moves along a circular arc of radius 100 micrometers inside a nonlinear crystal. The emitted radiation, in the terahertz frequency range, results from the nonlinear polarization induced by the pulse. The generation of synchrotron radiation from a pulse revolving about a circular trajectory holds promise for the development of on-chip terahertz sources.}, } @article {pmid30361368, year = {2018}, author = {Legnani, L and Prina-Cerai, G and Delcaillau, T and Willems, S and Morandi, B}, title = {Efficient access to unprotected primary amines by iron-catalyzed aminochlorination of alkenes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {434-439}, doi = {10.1126/science.aat3863}, pmid = {30361368}, issn = {1095-9203}, abstract = {Primary amines are essential constituents of biologically active molecules and versatile intermediates in the synthesis of drugs and agrochemicals. However, their preparation from easily accessible alkenes remains challenging. Here, we report a general strategy to access primary amines from alkenes through an operationally simple iron-catalyzed aminochlorination reaction. A stable hydroxylamine derivative and benign sodium chloride act as the respective nitrogen and chlorine sources. The reaction proceeds at room temperature under air; tolerates a large scope of aliphatic and conjugated alkenes, including densely functionalized substrates; and provides excellent anti-Markovnikov regioselectivity with respect to the amino group. The reactivity of the 2-chloroalkylamine products, an understudied class of amphoteric molecules, enables facile access to linear or branched aliphatic amines, aziridines, aminonitriles, azido amines, and homoallylic amines.}, } @article {pmid30361367, year = {2018}, author = {Ren, S and Wang, Y and Yue, F and Cheng, X and Dang, R and Qiao, Q and Sun, X and Li, X and Jiang, Q and Yao, J and Qin, H and Wang, G and Liao, X and Gao, D and Xia, J and Zhang, J and Hu, B and Yan, J and Wang, Y and Xu, M and Han, Y and Tang, X and Chen, X and He, C and Hu, Z}, title = {The paraventricular thalamus is a critical thalamic area for wakefulness.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {429-434}, doi = {10.1126/science.aat2512}, pmid = {30361367}, issn = {1095-9203}, mesh = {Animals ; Electrophysiology/methods ; Female ; Glutamic Acid ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Midline Thalamic Nuclei/*physiology ; Neurons/physiology ; Nucleus Accumbens/physiology ; Optogenetics ; Orexins/genetics ; Photometry/methods ; Proto-Oncogene Proteins c-fos/metabolism ; Wakefulness/*physiology ; }, abstract = {Clinical observations indicate that the paramedian region of the thalamus is a critical node for controlling wakefulness. However, the specific nucleus and neural circuitry for this function remain unknown. Using in vivo fiber photometry or multichannel electrophysiological recordings in mice, we found that glutamatergic neurons of the paraventricular thalamus (PVT) exhibited high activities during wakefulness. Suppression of PVT neuronal activity caused a reduction in wakefulness, whereas activation of PVT neurons induced a transition from sleep to wakefulness and an acceleration of emergence from general anesthesia. Moreover, our findings indicate that the PVT-nucleus accumbens projections and hypocretin neurons in the lateral hypothalamus to PVT glutamatergic neurons' projections are the effector pathways for wakefulness control. These results demonstrate that the PVT is a key wakefulness-controlling nucleus in the thalamus.}, } @article {pmid30361366, year = {2018}, author = {Zhu, Y and Nachtrab, G and Keyes, PC and Allen, WE and Luo, L and Chen, X}, title = {Dynamic salience processing in paraventricular thalamus gates associative learning.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {423-429}, doi = {10.1126/science.aat0481}, pmid = {30361366}, issn = {1095-9203}, support = {T32 DA035165/DA/NIDA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Conditioning, Classical/*physiology ; Cues ; Male ; Mice ; Mice, Inbred C57BL ; Midline Thalamic Nuclei/*physiology ; Neurons/*physiology ; Reward ; }, abstract = {The salience of behaviorally relevant stimuli is dynamic and influenced by internal state and external environment. Monitoring such changes is critical for effective learning and flexible behavior, but the neuronal substrate for tracking the dynamics of stimulus salience is obscure. We found that neurons in the paraventricular thalamus (PVT) are robustly activated by a variety of behaviorally relevant events, including novel ("unfamiliar") stimuli, reinforcing stimuli and their predicting cues, as well as omission of the expected reward. PVT responses are scaled with stimulus intensity and modulated by changes in homeostatic state or behavioral context. Inhibition of the PVT responses suppresses appetitive or aversive associative learning and reward extinction. Our findings demonstrate that the PVT gates associative learning by providing a dynamic representation of stimulus salience.}, } @article {pmid30361365, year = {2018}, author = {Woodard, JD and Sherrick, BJ and Atwood, DM and Blair, R and Fogel, G and Goeser, N and Gold, B and Lewis, J and Mattson, C and Moseley, J and O'Mara, C and Piotti, J and Salas, B and Scarlett, L and Duncanson, KW and Yoder, F}, title = {The power of agricultural data.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {410-411}, doi = {10.1126/science.aav5002}, pmid = {30361365}, issn = {1095-9203}, mesh = {Agriculture/*legislation & jurisprudence ; *Data Collection ; United States ; United States Department of Agriculture/*legislation & jurisprudence ; }, } @article {pmid30361364, year = {2018}, author = {Adelman, ZN and Albritton, LM and Boris-Lawrie, K and Buchmeier, MJ and Cannon, P and Cho, M and DiGiusto, D and Donahue, JK and Federoff, HJ and Hammarskjold, ML and Hardison, AD and Hearing, P and Lee, B and Lee, DA and Porteus, MH and Ross, LF and Ross, SR and Wooley, DP and Zoloth, L}, title = {Protect NIH's DNA advisory committee.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {409-410}, doi = {10.1126/science.aav2483}, pmid = {30361364}, issn = {1095-9203}, mesh = {Advisory Committees/*standards ; Containment of Biohazards ; *DNA, Recombinant ; Genetic Therapy/*standards ; Guidelines as Topic ; Humans ; National Institutes of Health (U.S.)/*standards ; United States ; }, } @article {pmid30361363, year = {2018}, author = {Florens, FBV and Vincenot, CE}, title = {Broader conservation strategies needed.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {409}, doi = {10.1126/science.aav5161}, pmid = {30361363}, issn = {1095-9203}, mesh = {Animals ; Biodiversity ; *Chiroptera ; *Endangered Species ; Mauritania ; }, } @article {pmid30361362, year = {2018}, author = {Dos S Ribeiro, C and Koopmans, MP and Haringhuizen, GB}, title = {Threats to timely sharing of pathogen sequence data.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {404-406}, doi = {10.1126/science.aau5229}, pmid = {30361362}, issn = {1095-9203}, mesh = {Bacteria/*genetics/pathogenicity ; Base Sequence/genetics ; Biological Specimen Banks ; Communicable Diseases, Emerging/*microbiology/virology ; *Global Health ; Humans ; *Information Dissemination ; International Cooperation ; Public Health ; Viruses/*genetics/pathogenicity ; }, } @article {pmid30361361, year = {2018}, author = {Pimiento, C}, title = {Our shallow-water origins.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {402-403}, doi = {10.1126/science.aau8461}, pmid = {30361361}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Ecosystem ; *Vertebrates ; Water ; }, } @article {pmid30361360, year = {2018}, author = {Taipale, J}, title = {The chromatin of cancer.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {401-402}, doi = {10.1126/science.aav3494}, pmid = {30361360}, issn = {1095-9203}, mesh = {*Chromatin ; Chromatin Assembly and Disassembly ; Gene Expression Regulation, Neoplastic ; Histones/genetics ; Humans ; Neoplasms/*genetics ; }, } @article {pmid30361359, year = {2018}, author = {Lupini, AR and Oxley, MP and Kalinin, SV}, title = {Pushing the limits of electron ptychography.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {399-400}, doi = {10.1126/science.aau7620}, pmid = {30361359}, issn = {1095-9203}, } @article {pmid30361358, year = {2018}, author = {Ehmke, H}, title = {The mechanotransduction of blood pressure.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {398-399}, doi = {10.1126/science.aav3495}, pmid = {30361358}, issn = {1095-9203}, mesh = {*Blood Pressure ; Blood Pressure Determination ; *Mechanotransduction, Cellular ; Stress, Mechanical ; }, } @article {pmid30361357, year = {2018}, author = {Gante, HF}, title = {How fish get their stripes-again and again.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {396-397}, doi = {10.1126/science.aav3373}, pmid = {30361357}, issn = {1095-9203}, mesh = {Animals ; *Fishes ; }, } @article {pmid30361356, year = {2018}, author = {Oransky, I}, title = {Volunteer watchdogs pushed a small country up the rankings.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {395}, doi = {10.1126/science.362.6413.395}, pmid = {30361356}, issn = {1095-9203}, } @article {pmid30361355, year = {2018}, author = {McCook, A}, title = {Fallout for co-authors.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {394-395}, doi = {10.1126/science.362.6413.394-b}, pmid = {30361355}, issn = {1095-9203}, } @article {pmid30361354, year = {2018}, author = {Marcus, A}, title = {A scientist's fraudulent studies put patients at risk.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {394}, doi = {10.1126/science.362.6413.394-a}, pmid = {30361354}, issn = {1095-9203}, mesh = {Administration, Intravenous ; Biomedical Research/*ethics ; Humans ; Hydroxyethyl Starch Derivatives/administration & dosage/*adverse effects ; Kidney Diseases/*chemically induced ; *Patient Safety ; Pharmaceutical Solutions/administration & dosage/adverse effects ; Risk ; *Scientific Misconduct ; }, } @article {pmid30361353, year = {2018}, author = {McCook, A}, title = {One publisher, more than 7000 retractions.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {393}, doi = {10.1126/science.362.6413.393}, pmid = {30361353}, issn = {1095-9203}, } @article {pmid30361352, year = {2018}, author = {Brainard, J}, title = {Rethinking retractions.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {390-393}, doi = {10.1126/science.362.6413.390}, pmid = {30361352}, issn = {1095-9203}, } @article {pmid30361351, year = {2018}, author = {Service, RF}, title = {Molecular CT scan could speed drug discovery.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {389}, doi = {10.1126/science.362.6413.389}, pmid = {30361351}, issn = {1095-9203}, mesh = {Drug Discovery/*methods ; Microscopy, Electron, Scanning Transmission/*methods ; Molecular Structure ; X-Ray Diffraction/*methods ; }, } @article {pmid30361350, year = {2018}, author = {Pennisi, E}, title = {Restoring lost grazers could help blunt climate change.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {388}, doi = {10.1126/science.362.6413.388}, pmid = {30361350}, issn = {1095-9203}, mesh = {Animals ; *Climate Change ; Conservation of Natural Resources/*methods ; Forests ; Grassland ; *Herbivory ; Perissodactyla ; Reindeer ; Tundra ; Wildfires/*prevention & control ; }, } @article {pmid30361349, year = {2018}, author = {Rosen, J}, title = {Youth climate trial showcases science.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {386-387}, doi = {10.1126/science.362.6413.386}, pmid = {30361349}, issn = {1095-9203}, } @article {pmid30361348, year = {2018}, author = {Price, M}, title = {Giant study links DNA to same-sex experiences.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {385-386}, doi = {10.1126/science.362.6413.385}, pmid = {30361348}, issn = {1095-9203}, mesh = {Chromosomes, Human/genetics ; DNA/genetics ; Genetic Markers ; Genetic Variation ; *Genome-Wide Association Study ; Homosexuality/*psychology ; Humans ; }, } @article {pmid30361347, year = {2018}, author = {Normile, D}, title = {China fosters competition in its race to exascale computing.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {384-385}, doi = {10.1126/science.362.6413.384}, pmid = {30361347}, issn = {1095-9203}, } @article {pmid30361346, year = {2018}, author = {Servick, K}, title = {U.S. labs clamor for marmosets.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {383-384}, doi = {10.1126/science.362.6413.383}, pmid = {30361346}, issn = {1095-9203}, mesh = {*Animal Experimentation ; Animals ; Animals, Genetically Modified ; *Animals, Laboratory ; *Callithrix ; Disease Models, Animal ; *Nervous System Diseases ; }, } @article {pmid30361345, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {380-382}, doi = {10.1126/science.362.6413.380}, pmid = {30361345}, issn = {1095-9203}, } @article {pmid30361344, year = {2018}, author = {Berg, J}, title = {Imagine a world without facts.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {379}, doi = {10.1126/science.aav7494}, pmid = {30361344}, issn = {1095-9203}, } @article {pmid30361343, year = {2018}, author = {Hershkovitz, I and Duval, M and Grün, R and Mercier, N and Valladas, H and Ayalon, A and Bar-Matthews, M and Weber, GW and Quam, R and Zaidner, Y and Weinstein-Evron, M}, title = {Response to Comment on "The earliest modern humans outside Africa".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aat8964}, pmid = {30361343}, issn = {1095-9203}, mesh = {Africa ; Animals ; *Biological Evolution ; *Fossils ; Hominidae ; Humans ; Israel ; }, abstract = {Our original claim, based on three independent numerical dating methods, of an age of ~185,000 years for the Misliya-1 modern human hemi-maxilla from Mount Carmel, Israel, is little affected by discounting uranium-series dating of adhering crusts. It confirms a much earlier out-of-Africa Homo sapiens expansion than previously suggested by the considerably younger (90,000 to 120,000 years) Skhul/Qafzeh hominins.}, } @article {pmid30361342, year = {2018}, author = {Sharp, WD and Paces, JB}, title = {Comment on "The earliest modern humans outside Africa".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aat6598}, pmid = {30361342}, issn = {1095-9203}, mesh = {Africa ; Animals ; *Fossils ; *Hominidae ; Humans ; Maxilla ; Time ; }, abstract = {Hershkovitz et al (Reports, 26 January 2018, p. 456) interpreted the Misliya-1 fossil maxilla as evidence of the earliest known anatomically modern human outside Africa. However, the fossil's reported age of 177,000 to 194,000 years relies on flawed interpretations of uranium-series data. We contend that those data support a minimum age of no more than ~60,000 to 70,000 years.}, } @article {pmid30361341, year = {2018}, author = {Corces, MR and Granja, JM and Shams, S and Louie, BH and Seoane, JA and Zhou, W and Silva, TC and Groeneveld, C and Wong, CK and Cho, SW and Satpathy, AT and Mumbach, MR and Hoadley, KA and Robertson, AG and Sheffield, NC and Felau, I and Castro, MAA and Berman, BP and Staudt, LM and Zenklusen, JC and Laird, PW and Curtis, C and , and Greenleaf, WJ and Chang, HY}, title = {The chromatin accessibility landscape of primary human cancers.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aav1898}, pmid = {30361341}, issn = {1095-9203}, support = {U24 CA210978/CA/NCI NIH HHS/United States ; K99 AG059918/AG/NIA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U24 CA210950/CA/NCI NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; U24 CA210974/CA/NCI NIH HHS/United States ; U24 CA210989/CA/NCI NIH HHS/United States ; U24 CA210952/CA/NCI NIH HHS/United States ; U24 CA210949/CA/NCI NIH HHS/United States ; R35 CA209919/CA/NCI NIH HHS/United States ; U24 CA210969/CA/NCI NIH HHS/United States ; U24 CA210988/CA/NCI NIH HHS/United States ; U24 CA210990/CA/NCI NIH HHS/United States ; }, mesh = {Chromatin/genetics/*metabolism ; DNA Footprinting ; Enhancer Elements, Genetic ; *Gene Expression Regulation, Neoplastic ; Genetic Loci ; *Genetic Predisposition to Disease ; Humans ; Immunity/genetics ; Neoplasms/*genetics/*metabolism ; *Regulatory Sequences, Nucleic Acid ; Transcription Factors/metabolism ; Transposases/metabolism ; }, abstract = {We present the genome-wide chromatin accessibility profiles of 410 tumor samples spanning 23 cancer types from The Cancer Genome Atlas (TCGA). We identify 562,709 transposase-accessible DNA elements that substantially extend the compendium of known cis-regulatory elements. Integration of ATAC-seq (the assay for transposase-accessible chromatin using sequencing) with TCGA multi-omic data identifies a large number of putative distal enhancers that distinguish molecular subtypes of cancers, uncovers specific driving transcription factors via protein-DNA footprints, and nominates long-range gene-regulatory interactions in cancer. These data reveal genetic risk loci of cancer predisposition as active DNA regulatory elements in cancer, identify gene-regulatory interactions underlying cancer immune evasion, and pinpoint noncoding mutations that drive enhancer activation and may affect patient survival. These results suggest a systematic approach to understanding the noncoding genome in cancer to advance diagnosis and therapy.}, } @article {pmid30361340, year = {2018}, author = {Bintu, B and Mateo, LJ and Su, JH and Sinnott-Armstrong, NA and Parker, M and Kinrot, S and Yamaya, K and Boettiger, AN and Zhuang, X}, title = {Super-resolution chromatin tracing reveals domains and cooperative interactions in single cells.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aau1783}, pmid = {30361340}, issn = {1095-9203}, support = {R35 GM122487/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {CCCTC-Binding Factor/chemistry ; Cell Cycle Proteins/chemistry ; Chromatin/*chemistry/ultrastructure ; Chromosomal Proteins, Non-Histone/chemistry ; Genome, Human ; HCT116 Cells ; Humans ; In Situ Hybridization, Fluorescence ; Protein Binding ; Protein Domains ; Single-Cell Analysis/*methods ; }, abstract = {The spatial organization of chromatin is pivotal for regulating genome functions. We report an imaging method for tracing chromatin organization with kilobase- and nanometer-scale resolution, unveiling chromatin conformation across topologically associating domains (TADs) in thousands of individual cells. Our imaging data revealed TAD-like structures with globular conformation and sharp domain boundaries in single cells. The boundaries varied from cell to cell, occurring with nonzero probabilities at all genomic positions but preferentially at CCCTC-binding factor (CTCF)- and cohesin-binding sites. Notably, cohesin depletion, which abolished TADs at the population-average level, did not diminish TAD-like structures in single cells but eliminated preferential domain boundary positions. Moreover, we observed widespread, cooperative, multiway chromatin interactions, which remained after cohesin depletion. These results provide critical insight into the mechanisms underlying chromatin domain and hub formation.}, } @article {pmid30361339, year = {2018}, author = {Silveyra, JM and Ferrara, E and Huber, DL and Monson, TC}, title = {Soft magnetic materials for a sustainable and electrified world.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aao0195}, pmid = {30361339}, issn = {1095-9203}, abstract = {Soft magnetic materials are key to the efficient operation of the next generation of power electronics and electrical machines (motors and generators). Many new materials have been introduced since Michael Faraday's discovery of magnetic induction, when iron was the only option. However, as wide bandgap semiconductor devices become more common in both power electronics and motor controllers, there is an urgent need to further improve soft magnetic materials. These improvements will be necessary to realize the full potential in efficiency, size, weight, and power of high-frequency power electronics and high-rotational speed electrical machines. Here we provide an introduction to the field of soft magnetic materials and their implementation in power electronics and electrical machines. Additionally, we review the most promising choices available today and describe emerging approaches to create even better soft magnetic materials.}, } @article {pmid30361068, year = {2018}, author = {Pagel, M}, title = {Parameter Estimation in a Biogeographical Context.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {897-898}, doi = {10.1016/j.tree.2018.09.009}, pmid = {30361068}, issn = {1872-8383}, } @article {pmid30361058, year = {2018}, author = {Uecker, H}, title = {Effectively Evolution-proof Antibiotics?.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {969-970}, doi = {10.1016/j.tim.2018.09.002}, pmid = {30361058}, issn = {1878-4380}, } @article {pmid30361057, year = {2018}, author = {Bell, G and MacLean, C}, title = {Evolution-proof Antibiotics: Response to Uecker.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {970-971}, doi = {10.1016/j.tim.2018.10.001}, pmid = {30361057}, issn = {1878-4380}, } @article {pmid30360957, year = {2018}, author = {Hobbs, EC and Trevisan, C and Johansen, MV and Dorny, P and Gabriël, S}, title = {Value of Electronic Educational Media in Combatting Parasitic Diseases.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.10.001}, pmid = {30360957}, issn = {1471-5007}, abstract = {Parasitic diseases have plagued mankind throughout history, and even today parasites continue to cause disease, disability and death in millions of people worldwide. Targeted electronic educational media for bringing awareness to local inhabitants of endemic communities, including public health practitioners, are vital tools in the battle against parasitic diseases.}, } @article {pmid30359746, year = {2019}, author = {Sandoval-Huerta, ER and Beltrán-López, RG and Pedraza-Marrón, CR and Paz-Velásquez, MA and Angulo, A and Robertson, DR and Espinoza, E and Domínguez-Domínguez, O}, title = {The evolutionary history of the goby Elacatinus puncticulatus in the tropical eastern pacific: Effects of habitat discontinuities and local environmental variability.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {269-285}, doi = {10.1016/j.ympev.2018.10.020}, pmid = {30359746}, issn = {1095-9513}, abstract = {Habitat discontinuities, temperature gradients, upwelling systems, and ocean currents, gyres and fronts, can affect distributions of species with narrow environmental tolerance or motility and influence the dispersal of pelagic larvae, with effects ranging from the isolation of adjacent populations to connections between them. The coast of the Tropical Eastern Pacific (TEP) is a highly dynamic environment, with various large gyres and upwelling systems, alternating currents and large rocky-habitat discontinuities, which may greatly influence the genetic connectivity of populations in different parts of the coast. Elacatinus puncticulatus is a cryptic, shallow-living goby that is distributed along the continental shore of virtually the entire TEP, which makes it a good model for testing the influence of these environmental characteristics in the molecular evolution of widespread species in this region. A multilocus phylogeny was used to evaluate the influence of habitat gaps, and oceanographic processes in the evolutionary history of E. puncticulatus throughout its geographical range in the TEP. Two well-supported allopatric clades (one with two allopatric subclades) were recovered, the geographic distribution of which does not correspond to any previously proposed major biogeographic provinces. These populations show strong genetic structure and substantial genetic distances between clades and sub-clades (cytb 0.8-7.3%), with divergence times between them ranging from 0.53 to 4.88 Mya, and recent population expansions dated at 170-130 Kya. The ancestral area of all populations appears to be the Gulf of Panama, while several isolation events have formed the phylogeographic patterns evident in this species. Local and regional oceanographic processes as well as habitat discontinuities have shaped the distribution patterns of the genetic lineages along the continental TEP. Large genetic distances, high genetic differentiation, and the results of species-tree and phylogenetic analyses indicate that E. puncticulatus comprises a complex of three allopatric species with an unusual geographic arrangement.}, } @article {pmid30359745, year = {2019}, author = {Kieran, TJ and Gordon, ERL and Forthman, M and Hoey-Chamberlain, R and Kimball, RT and Faircloth, BC and Weirauch, C and Glenn, TC}, title = {Insight from an ultraconserved element bait set designed for hemipteran phylogenetics integrated with genomic resources.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {297-303}, doi = {10.1016/j.ympev.2018.10.026}, pmid = {30359745}, issn = {1095-9513}, abstract = {Target enrichment of conserved genomic regions facilitates collecting sequences of many orthologous loci from non-model organisms to address phylogenetic, phylogeographic, population genetic, and molecular evolution questions. Bait sets for sequence capture can simultaneously target thousands of loci, which opens new avenues of research on speciose groups. Current phylogenetic hypotheses on the >103,000 species of Hemiptera have failed to unambiguously resolve major nodes, suggesting that alternative datasets and more thorough taxon sampling may be required to resolve relationships. We use a recently designed ultraconserved element (UCE) bait set for Hemiptera, with a focus on the suborder Heteroptera, or the true bugs, to test previously proposed relationships. We present newly generated UCE data for 36 samples representing three suborders, all seven heteropteran infraorders, 23 families, and 34 genera of Hemiptera and one thysanopteran outgroup. To improve taxon sampling, we also mined additional UCE loci in silico from published hemipteran genomic and transcriptomic data. We obtained 2271 UCE loci for newly sequenced hemipteran taxa, ranging from 265 to 1696 (average 904) per sample. These were similar in number to the data mined from transcriptomes and genomes, but with fewer loci overall. The amount of missing data correlates with greater phylogenetic divergence from taxa used to design the baits. This bait set hybridizes to a wide range of hemipteran taxa and specimens of varying quality, including dried specimens as old as 1973. Our estimated phylogeny yielded topologies consistent with other studies for most nodes and was strongly-supported. We also demonstrate that UCE loci are almost exclusively from the transcribed portion of the genome, thus data can be successfully integrated with existing genomic and transcriptomic resources for more comprehensive phylogenetic sampling, an important feature in the era of phylogenomics. UCE approaches can be used by other researchers for additional studies on hemipteran evolution and other research that requires well resolved phylogenies.}, } @article {pmid30359560, year = {2019}, author = {Mehravar, M and Shirazi, A and Nazari, M and Banan, M}, title = {Mosaicism in CRISPR/Cas9-mediated genome editing.}, journal = {Developmental biology}, volume = {445}, number = {2}, pages = {156-162}, doi = {10.1016/j.ydbio.2018.10.008}, pmid = {30359560}, issn = {1095-564X}, abstract = {The CRISPR/Cas9 system is a rapid, simple, and often extremely efficient gene editing method. This method has been used in a variety of organisms and cell types over the past several years. However, using this technology for generating gene-edited animals involves a number of obstacles. One such obstacle is mosaicism, which is common in founder animals. This is especially the case when the CRISPR/Cas9 system is used in embryos. Here we review the pros and cons of mosaic mutations of gene-edited animals caused by using the CRISPR/Cas9 system in embryos. Furthermore, we will discuss the mechanisms underlying mosaic mutations resulting from the CRISPR/Cas9 system, as well as the possible strategies for reducing mosaicism. By developing ways to overcome mosaic mutations when using CRISPR/Cas9, genotyping for germline gene disruptions should become more reliable. This achievement will pave the way for using the CRISPR technology in the research and clinical applications where mosaicism is an issue.}, } @article {pmid30359301, year = {2018}, author = {Hii, SYF and Ahmad, N and Hashim, R and Liow, YL and Abd Wahab, MA and Mohd Khalid, MKN}, title = {A SNP-based phylogenetic analysis of Corynebacterium diphtheriae in Malaysia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {760}, pmid = {30359301}, issn = {1756-0500}, support = {NMRR id: 16-1421-32070 (JPP-IMR: 16-056)//Ministry of Health Malaysia/ ; }, mesh = {Corynebacterium diphtheriae/*classification/*genetics ; Diphtheria/*microbiology/*prevention & control ; *Diphtheria Toxoid/pharmacology ; Genome, Bacterial/*genetics ; Humans ; Malaysia ; *Phylogeny ; }, abstract = {OBJECTIVE: There is a lack of study in Corynebacterium diphtheriae isolates in Malaysia. The alarming surge of cases in year 2016 lead us to evaluate the local clinical C. diphtheriae strains in Malaysia. We conducted single nucleotide polymorphism phylogenetic analysis on the core and pan-genome as well as toxin and diphtheria toxin repressor (DtxR) genes of Malaysian C. diphtheriae isolates from the year 1986-2016.

RESULTS: The comparison between core and pan-genomic comparison showed variation in the distribution of C. diphtheriae. The local isolates portrayed a heterogenous trait and a close relationship between Malaysia's and Belarus's, Africa's and India's strains were observed. A toxigenic C. diphtheriae clone was noted to be circulating in the Malaysian population for nearly 30 years and from our study, the non-toxigenic and toxigenic C. diphtheriae strains can be differentiated significantly into two large clusters, A and B respectively. Analysis against vaccine strain, PW8 portrayed that the amino acid composition of toxin and DtxR in Malaysia's local strains are well-conserved and there was no functional defect noted. Hence, the change in efficacy of the currently used toxoid vaccine is unlikely to occur.}, } @article {pmid30359300, year = {2018}, author = {Twetman, S and Pedersen, AML and Yucel-Lindberg, T}, title = {Probiotic supplements containing Lactobacillus reuteri does not affect the levels of matrix metalloproteinases and interferons in oral wound healing.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {759}, pmid = {30359300}, issn = {1756-0500}, mesh = {Adult ; Aged ; Cross-Over Studies ; *Dietary Supplements ; Double-Blind Method ; Female ; Humans ; Interferons/*drug effects ; *Lactobacillus reuteri ; Male ; Matrix Metalloproteinases/*drug effects ; Middle Aged ; Mouth Mucosa/*drug effects/*injuries ; Pilot Projects ; Probiotics/administration & dosage/*pharmacology ; Treatment Failure ; Wound Healing/*drug effects ; Young Adult ; }, abstract = {OBJECTIVE: The use of beneficial bacteria may stimulate wound healing. We performed a randomized, placebo-controlled double-blind cross-over study comprising ten healthy volunteers. The aim was to investigate the impact of topical and systemic applications of probiotic lactobacilli (Lactobacillus reuteri) on the healing of standardized wounds (punch biopsies) in the oral mucosa. The expression of selected matrix metalloproteinases (MMP'S) and interferons (IFN's) was analyzed with multiplex immunoassays in the wound exudate during the first healing week (day 2, 5 and 8).

RESULTS: All participants completed the study and in all cases, the healing after the punch biopsies was uneventful. The concentrations of MMP-1, MMP-2, MMP-3 decreased with time in both the test- and control group. The MMP levels were consistently lower during the probiotic intervention when compared with placebo but the differences were not statistically significant. Likewise, the concentrations if IFN-alpha2, IFN-beta and IFN-gamma decreased with time with no significant differences between the test and placebo interventions. Within the limitations of this pilot study, we were unable to demonstrate an influence of probiotic supplements containing L. reuteri on the concentrations of selected matrix metalloproteinases and interferons from mucosal wounds within 1 week after a standardized punch biopsy. Trial registration ClinicalTrials.gov Identifier NCT03210779. Date of registration: July 7, 2017.}, } @article {pmid30359295, year = {2018}, author = {Chapleau, RR and Martin, CA and Hughes, SR and Baldwin, JC and Sladky, J and Sherman, PM and Grinkemeyer, M}, title = {Evaluating apolipoprotein E genotype status and neuroprotective effects against white matter hyperintensity development in high-altitude careers.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {764}, pmid = {30359295}, issn = {1756-0500}, mesh = {*Altitude ; Apolipoproteins E/*genetics ; Humans ; Leukoaraiosis/*etiology/*genetics ; Male ; Neuroprotection/*genetics ; Occupational Diseases/*etiology ; Pilots ; }, abstract = {OBJECTIVE: This study considers the use of a rapid molecular assay to evaluate apolipoprotein E (ApoE) status in military subjects who have been exposed to high altitude. We hypothesize that ApoE status may be protective against developing brain white matter hyperintensities (WMHs) after high altitude exposure.

RESULTS: We tested 92 subjects who had been exposed to altitudes above 25,000 ft mean sea level, either as pilots or as altitude chamber technicians. We determined subject genetic status using rapid Taqman-style polymerase chain reaction genotyping and evaluated the association of ApoE subtype versus brain lesions using t-tests and two-way analyses of variance. Our results indicate that there is no significant association between ApoE genotype status and the presence of WMHs after high altitude exposure. We did observe a significantly higher number of hours spent at altitude for subjects with the ApoE E2 allele; however, the mechanism by which this may occur is not determined in this study. To more fully elucidate this effect, larger populations would be required to observe greater numbers of subjects with the E2 and E4 alleles.}, } @article {pmid30359291, year = {2018}, author = {Meyerholz, DK and Beck, AP and Goeken, JA and Leidinger, MR and Ofori-Amanfo, GK and Brown, HC and Businga, TR and Stoltz, DA and Reznikov, LR and Flaherty, HA}, title = {Glycogen depletion can increase the specificity of mucin detection in airway tissues.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {763}, pmid = {30359291}, issn = {1756-0500}, support = {P01 HL091842/HL/NHLBI NIH HHS/United States ; UIOWA//Cystic Fibrosis Foundation/ ; R01 HL136813/HL/NHLBI NIH HHS/United States ; OT2 OD023854/OD/NIH HHS/United States ; P01 HL051670/HL/NHLBI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; R00 HL119560/HL/NHLBI NIH HHS/United States ; HL091842//National Heart, Lung, and Blood Institute/ ; DK54759//National Institute of Diabetes and Digestive and Kidney Diseases/ ; P30 DK054759/DK/NIDDK NIH HHS/United States ; HL136813//National Heart, Lung, and Blood Institute/ ; HL51670//National Heart, Lung, and Blood Institute/ ; HL119560//National Heart, Lung, and Blood Institute/ ; K99 HL119560/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Female ; Glycogen/*metabolism ; Liver/*metabolism ; Male ; Mice ; Mucins/*metabolism ; Periodic Acid-Schiff Reaction/*methods/standards ; Respiratory Mucosa/*metabolism ; Sensitivity and Specificity ; Staining and Labeling/*methods/standards ; Swine ; Trachea/*metabolism ; }, abstract = {OBJECTIVE: Mucin is an important parameter for detection and assessment in studies of airway disease including asthma and cystic fibrosis. Histochemical techniques are often used to evaluate mucin in tissues sections. Periodic acid Schiff (PAS) is a common technique to detect neutral mucins in tissue, but this technique also detects other tissue components including cellular glycogen. We tested whether depletion of glycogen, a common cellular constituent, could impact the detection of mucin in the surface epithelium of the trachea.

RESULTS: Normal tissues stained by PAS had significantly more staining than serial sections of glycogen-depleted tissue with PAS staining (i.e. dPAS technique) based on both quantitative analysis and semiquantitative scores. Most of the excess stain by the PAS technique was detected in ciliated cells adjacent to goblet cells. We also compared normal tissues using the Alcian blue technique, which does not have reported glycogen staining, with the dPAS technique. These groups had similar amounts of staining consistent with a high degree of mucin specificity. Our results suggest that when using PAS techniques to stain airways, the dPAS approach is preferred as it enhances the specificity for airway mucin.}, } @article {pmid30359290, year = {2018}, author = {Nabaggala, MS and Parkes-Ratanshi, R and Kasirye, R and Kiragga, A and Castlenuovo, B and Ochaka, I and Nakakawa, L and Bena, DA and Mujugira, A}, title = {Re-engagement in HIV care following a missed visit in rural Uganda.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {762}, pmid = {30359290}, issn = {1756-0500}, support = {CSF 01-10-003//CS Fund/ ; D43 TW009771/TW/FIC NIH HHS/United States ; K4 TW010695//Fogarty International Center/ ; K43 TW010695/TW/FIC NIH HHS/United States ; D43 TW009771//Fogarty International Center/ ; P30 AI027757/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Antiretroviral Therapy, Highly Active/*statistics & numerical data ; *Appointments and Schedules ; Female ; HIV Infections/*drug therapy/epidemiology ; Humans ; Male ; Patient Compliance/*statistics & numerical data ; Patient Dropouts/*statistics & numerical data ; Retrospective Studies ; Uganda/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: We conducted a retrospective cohort study to assess the effect of tracking People Living with HIV (PLHIV) after missed clinic visits and factors associated with return to care in rural Uganda. We assessed retention in care among 650 HIV-infected women and men. We used univariable and multivariable generalized linear models to assess demographic and self-reported factors associated with re-engagement in HIV care.

RESULTS: Of 381 PLHIV who ever missed a scheduled appointment, 68% were female and most (80%) had initiated ART. Most (70%) of those tracked returned to care. Relative to men, women (adjusted risk ratio [ARR] 1.23; 95% confidence interval (CI) 1.05-1.43; p = 0.009) were more likely to return to care after active tracking. PLHIV who missed scheduled visits for other reasons (forgetting, adequate drug supplies, or long distance to clinic) had reduced odds of return to care (ARR 0.41; 95% CI 0.28-0.59; p < 0.001). These data support close monitoring of patient retention in HIV care and active measures to re-engage those who miss an appointment. Furthermore, they highlight the need for targeted interventions to those more resistant to re-engagement such as men.}, } @article {pmid30359289, year = {2018}, author = {Tadege, M}, title = {Time to death predictors of HIV/AIDS infected patients on antiretroviral therapy in Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {761}, pmid = {30359289}, issn = {1756-0500}, mesh = {Acquired Immunodeficiency Syndrome/drug therapy/mortality ; Adult ; Antiretroviral Therapy, Highly Active/*statistics & numerical data ; Comorbidity ; Ethiopia/epidemiology ; Female ; HIV Infections/*drug therapy/*mortality ; Humans ; Male ; Severity of Illness Index ; Time Factors ; Tuberculosis/*mortality ; }, abstract = {OBJECTIVE: The purpose of this study was to identify the major risk factors, which contributed to shortened survival time to death of HIV patients on antiretroviral therapy. Six-hundred HIV patients were included from two hospitals and six health centers record from January 2003 to December 2017. Kaplan-Meier and Cox proportional hazard model were implemented.

RESULTS: From the Kaplan-Meier, log-rank test result indicated that there was a significant difference between tuberculosis comorbidity (P = .000), occupation (P = .027), and WHO clinical stage (P = .012) on the survival experience of patients at 5% statistical significance level. From the Cox regression result, the risk of death for patients who lived with tuberculosis was about 2.872-fold times higher than those patients who were negative. Most of the HIV/AIDS patients on antiretroviral therapy were died in a short period due to tuberculosis comorbidity, began with lower amount of CD4, being underweight, merchant, and being on WHO clinical stage IV.}, } @article {pmid30359256, year = {2018}, author = {de Filippo, C and Meyer, M and Prüfer, K}, title = {Quantifying and reducing spurious alignments for the analysis of ultra-short ancient DNA sequences.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {121}, pmid = {30359256}, issn = {1741-7007}, abstract = {BACKGROUND: The study of ancient DNA is hampered by degradation, resulting in short DNA fragments. Advances in laboratory methods have made it possible to retrieve short DNA fragments, thereby improving access to DNA preserved in highly degraded, ancient material. However, such material contains large amounts of microbial contamination in addition to DNA fragments from the ancient organism. The resulting mixture of sequences constitutes a challenge for computational analysis, since microbial sequences are hard to distinguish from the ancient sequences of interest, especially when they are short.

RESULTS: Here, we develop a method to quantify spurious alignments based on the presence or absence of rare variants. We find that spurious alignments are enriched for mismatches and insertion/deletion differences and lack substitution patterns typical of ancient DNA. The impact of spurious alignments can be reduced by filtering on these features and by imposing a sample-specific minimum length cutoff. We apply this approach to sequences from four ~ 430,000-year-old Sima de los Huesos hominin remains, which contain particularly short DNA fragments, and increase the amount of usable sequence data by 17-150%. This allows us to place a third specimen from the site on the Neandertal lineage.

CONCLUSIONS: Our method maximizes the sequence data amenable to genetic analysis from highly degraded ancient material and avoids pitfalls that are associated with the analysis of ultra-short DNA sequences.}, } @article {pmid30359242, year = {2018}, author = {Zhang, D and Lou, X and Yan, H and Pan, J and Mao, H and Tang, H and Shu, Y and Zhao, Y and Liu, L and Li, J and Chen, J and Zhang, Y and Ma, X}, title = {Metagenomic analysis of viral nucleic acid extraction methods in respiratory clinical samples.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {773}, pmid = {30359242}, issn = {1471-2164}, support = {2016YFC1202700//Ministry of Science and Technology of the People's Republic of China/ ; 2016YFC1200903//Ministry of Science and Technology of the People's Republic of China/ ; 2017YFC1200503//Ministry of Science and Technology of the People's Republic of China/ ; 2017ZX10103008-002//Ministry of Science and Technology of the People's Republic of China/ ; }, abstract = {BACKGROUND: Numerous protocols for viral enrichment and genome amplification have been created. However, the direct identification of viral genomes from clinical specimens using next-generation sequencing (NGS) still has its challenges. As a selected viral nucleic acid extraction method may determine the sensitivity and reliability of NGS, it is still valuable to evaluate the extraction efficiency of different extraction kits using clinical specimens directly.

RESULTS: In this study, we performed qRT-PCR and viral metagenomic analysis of the extraction efficiency of four commonly used Qiagen extraction kits: QIAamp Viral RNA Mini Kit (VRMK), QIAamp MinElute Virus Spin Kit (MVSK), RNeasy Mini Kit (RMK), and RNeasy Plus Micro Kit (RPMK), using a mixed respiratory clinical sample without any pre-treatment. This sample contained an adenovirus (ADV), influenza virus A (Flu A), human parainfluenza virus 3 (PIV3), human coronavirus OC43 (OC43), and human metapneumovirus (HMPV). The quantity and quality of the viral extracts were significantly different among these kits. The highest threshold cycle(Ct)values for ADV and OC43 were obtained by using the RPMK. The MVSK had the lowest Ct values for ADV and PIV3. The RMK revealed the lowest detectability for HMPV and PIV3. The most effective rate of NGS data at 67.47% was observed with the RPMK. The other three kits ranged between 12.1-26.79% effectiveness rates for the NGS data. Most importantly, compared to the other three kits the highest proportion of non-host reads was obtained by the RPMK. The MVSK performed best with the lowest Ct value of 20.5 in the extraction of ADV, while the RMK revealed the best extraction efficiency by NGS analysis.

CONCLUSIONS: The evaluation of viral nucleic acid extraction efficiency is different between NGS and qRT-PCR analysis. The RPMK was most applicable for the metagenomic analysis of viral RNA and enabled more sensitive identification of the RNA virus genome in respiratory clinical samples. In addition, viral RNA extraction kits were also applicable for metagenomic analysis of the DNA virus. Our results highlighted the importance of nucleic acid extraction kit selection, which has a major impact on the yield and number of viral reads by NGS analysis. Therefore, the choice of extraction method for a given viral pathogen needs to be carefully considered.}, } @article {pmid30359236, year = {2018}, author = {Zhang, X and Li, T and Chen, X and Wang, S and Liu, Z}, title = {Nystatin enhances the immune response against Candida albicans and protects the ultrastructure of the vaginal epithelium in a rat model of vulvovaginal candidiasis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {166}, pmid = {30359236}, issn = {1471-2180}, support = {81571394//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Vulvovaginal candidiasis (VVC) is a common infectious disease of the lower genital tract. Nystatin, a polyene fungicidal antibiotic, is used as a topical antifungal agent for VVC treatment. The aim of the current study was to investigate the possible immunomodulatory effects of nystatin on the vaginal mucosal immune response during Candida albicans infection and examine its role in protection of vaginal epithelial cell (VEC) ultrastructure.

RESULTS: Following infection with C. albicans, IFN-γ and IL-17 levels in VECs were significantly elevated, while the presence of IgG was markedly decreased as compared to uninfected controls (P < 0.05). No significant differences in IL4 expression were observed. After treatment with nystatin, the level of IFN-γ, IL-17 and IgG was dramatically increased in comparison to the untreated group (P < 0.05). Transmission electron microscopy revealed that C. albicans invades the vaginal epithelium by both induced endocytosis and active penetration. Nystatin treatment protects the ultrastructure of the vaginal epithelium. Compared with the untreated C. albicans-infected group, Flameng scores which measure mitochondrial damage of VECs were markedly decreased (P < 0.001) and the number of adhesive and invasive C. albicans was significantly reduced (P < 0.01) after treatment with nystatin.

CONCLUSIONS: Nystatin plays a protective role in the host defense against C. albicans by up-regulating the IFN-γ-related cellular response, the IL-17 signaling pathway and possibly through enhancing VEC-derived IgG-mediated immunity. Furthermore, nystatin notably improves the ultramorphology of the vaginal mucosa, partially through the protection of mitochondria ultrastructure in VECs and inhibition of adhesion and invasion by C. albicans. Together, these effects enhance the immune response of the vaginal mucosa against C. albicans and protect the ultrastructure of vaginal epithelium in VVC rats.}, } @article {pmid30359224, year = {2018}, author = {Das, R and Upadhyai, P}, title = {Correction to: Application of geographic population structure (GPS) algorithm for biogeographical analyses of populations with complex ancestries: a case study of South Asians from 1000 genomes project.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {96}, pmid = {30359224}, issn = {1471-2156}, abstract = {Following publication of the original article [1], the authors flagged that acknowledgment of their equal contribution is omitted in the article [1].}, } @article {pmid30359080, year = {2018}, author = {Elf, J and Barkefors, I}, title = {Single-Molecule Kinetics in Living Cells.}, journal = {Annual review of biochemistry}, volume = {}, number = {}, pages = {}, doi = {10.1146/annurev-biochem-013118-110801}, pmid = {30359080}, issn = {1545-4509}, abstract = {In the past decades, advances in microscopy have made it possible to study the dynamics of individual biomolecules in vitro and resolve intramolecular kinetics that would otherwise be hidden in ensemble averages. More recently, single-molecule methods have been used to image, localize, and track individually labeled macromolecules in the cytoplasm of living cells, allowing investigations of intermolecular kinetics under physiologically relevant conditions. In this review, we illuminate the particular advantages of single-molecule techniques when studying kinetics in living cells and discuss solutions to specific challenges associated with these methods. Expected final online publication date for the Annual Review of Biochemistry Volume 88 is June 20, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}, } @article {pmid30358527, year = {2018}, author = {Shin, Y and Paek, J and Son, AY and Kim, H and Kook, JK and Paek, WK and Chang, YH}, title = {Clostridium composti sp. nov., a new anaerobic bacteria isolated from compost.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3869-3873}, doi = {10.1099/ijsem.0.003074}, pmid = {30358527}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Clostridium/*classification/genetics/isolation & purification ; *Composting ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fermentation ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {Strain YH-tan31T is a Gram-stain-positive, obligately anaerobic, spore-forming and mesophilic bacterium. The cells are rod-shaped and motile by means of peritrichous flagella. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the isolate belongs to the genus Clostridium and is most closely related to Clostridium oryzae DSM 28571T (97 % sequence identity), followed by Clostridium cellulovorans DSM 3052T (92.4 %) and Clostridium butyricum KCTC 5387T (92.1 %). The G+C content of the isolate was 30.9 mol%. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The predominant fatty acids were C14 : 0, C16 : 0, C16 : 0 DMA,and C19 : 0cis 11,12 DMA. The major end products of glucose fermentation were butyrate, acetate and lactate. This isolate represents a new species within the genus Clostridium, for which we propose the name Clostridiumcomposti sp. nov. (type strain, YH-tan31T; =KCTC 15630T=JCM 32793T).}, } @article {pmid30356220, year = {2018}, author = {Hagai, T and Chen, X and Miragaia, RJ and Rostom, R and Gomes, T and Kunowska, N and Henriksson, J and Park, JE and Proserpio, V and Donati, G and Bossini-Castillo, L and Vieira Braga, FA and Naamati, G and Fletcher, J and Stephenson, E and Vegh, P and Trynka, G and Kondova, I and Dennis, M and Haniffa, M and Nourmohammad, A and Lässig, M and Teichmann, SA}, title = {Gene expression variability across cells and species shapes innate immunity.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {197-202}, doi = {10.1038/s41586-018-0657-2}, pmid = {30356220}, issn = {1476-4687}, abstract = {As the first line of defence against pathogens, cells mount an innate immune response, which varies widely from cell to cell. The response must be potent but carefully controlled to avoid self-damage. How these constraints have shaped the evolution of innate immunity remains poorly understood. Here we characterize the innate immune response's transcriptional divergence between species and variability in expression among cells. Using bulk and single-cell transcriptomics in fibroblasts and mononuclear phagocytes from different species, challenged with immune stimuli, we map the architecture of the innate immune response. Transcriptionally diverging genes, including those that encode cytokines and chemokines, vary across cells and have distinct promoter structures. Conversely, genes that are involved in the regulation of this response, such as those that encode transcription factors and kinases, are conserved between species and display low cell-to-cell variability in expression. We suggest that this expression pattern, which is observed across species and conditions, has evolved as a mechanism for fine-tuned regulation to achieve an effective but balanced response.}, } @article {pmid30356219, year = {2018}, author = {Gaudinier, A and Rodriguez-Medina, J and Zhang, L and Olson, A and Liseron-Monfils, C and Bågman, AM and Foret, J and Abbitt, S and Tang, M and Li, B and Runcie, DE and Kliebenstein, DJ and Shen, B and Frank, MJ and Ware, D and Brady, SM}, title = {Transcriptional regulation of nitrogen-associated metabolism and growth.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {259-264}, doi = {10.1038/s41586-018-0656-3}, pmid = {30356219}, issn = {1476-4687}, abstract = {Nitrogen is an essential macronutrient for plant growth and basic metabolic processes. The application of nitrogen-containing fertilizer increases yield, which has been a substantial factor in the green revolution1. Ecologically, however, excessive application of fertilizer has disastrous effects such as eutrophication2. A better understanding of how plants regulate nitrogen metabolism is critical to increase plant yield and reduce fertilizer overuse. Here we present a transcriptional regulatory network and twenty-one transcription factors that regulate the architecture of root and shoot systems in response to changes in nitrogen availability. Genetic perturbation of a subset of these transcription factors revealed coordinate transcriptional regulation of enzymes involved in nitrogen metabolism. Transcriptional regulators in the network are transcriptionally modified by feedback via genetic perturbation of nitrogen metabolism. The network, genes and gene-regulatory modules identified here will prove critical to increasing agricultural productivity.}, } @article {pmid30356218, year = {2018}, author = {Katsyuba, E and Mottis, A and Zietak, M and De Franco, F and van der Velpen, V and Gariani, K and Ryu, D and Cialabrini, L and Matilainen, O and Liscio, P and Giacchè, N and Stokar-Regenscheit, N and Legouis, D and de Seigneux, S and Ivanisevic, J and Raffaelli, N and Schoonjans, K and Pellicciari, R and Auwerx, J}, title = {De novo NAD+ synthesis enhances mitochondrial function and improves health.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {354-359}, doi = {10.1038/s41586-018-0645-6}, pmid = {30356218}, issn = {1476-4687}, abstract = {Nicotinamide adenine dinucleotide (NAD+) is a co-substrate for several enzymes, including the sirtuin family of NAD+-dependent protein deacylases. Beneficial effects of increased NAD+ levels and sirtuin activation on mitochondrial homeostasis, organismal metabolism and lifespan have been established across species. Here we show that α-amino-β-carboxymuconate-ε-semialdehyde decarboxylase (ACMSD), the enzyme that limits spontaneous cyclization of α-amino-β-carboxymuconate-ε-semialdehyde in the de novo NAD+ synthesis pathway, controls cellular NAD+ levels via an evolutionarily conserved mechanism in Caenorhabditis elegans and mouse. Genetic and pharmacological inhibition of ACMSD boosts de novo NAD+ synthesis and sirtuin 1 activity, ultimately enhancing mitochondrial function. We also characterize two potent and selective inhibitors of ACMSD. Because expression of ACMSD is largely restricted to kidney and liver, these inhibitors may have therapeutic potential for protection of these tissues from injury. In summary, we identify ACMSD as a key modulator of cellular NAD+ levels, sirtuin activity and mitochondrial homeostasis in kidney and liver.}, } @article {pmid30356217, year = {2018}, author = {Kraft-Todd, GT and Bollinger, B and Gillingham, K and Lamp, S and Rand, DG}, title = {Credibility-enhancing displays promote the provision of non-normative public goods.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {245-248}, doi = {10.1038/s41586-018-0647-4}, pmid = {30356217}, issn = {1476-4687}, support = {DE-EE0006128//US Department of Energy/International ; }, abstract = {Promoting the adoption of public goods that are not yet widely accepted is particularly challenging. This is because most tools for increasing cooperation-such as reputation concerns1 and information about social norms2-are typically effective only for behaviours that are commonly practiced, or at least generally agreed upon as being desirable. Here we examine how advocates can successfully promote non-normative (that is, rare or unpopular) public goods. We do so by applying the cultural evolutionary theory of credibility-enhancing displays3, which argues that beliefs are spread more effectively by actions than by words alone-because actions provide information about the actor's true beliefs. Based on this logic, people who themselves engage in a given behaviour will be more effective advocates for that behaviour than people who merely extol its virtues-specifically because engaging in a behaviour credibly signals a belief in its value. As predicted, a field study of a programme that promotes residential solar panel installation in 58 towns in the United States-comprising 1.4 million residents in total-found that community organizers who themselves installed through the programme recruited 62.8% more residents to install solar panels than community organizers who did not. This effect was replicated in three pre-registered randomized survey experiments (total n = 1,805). These experiments also support the theoretical prediction that this effect is specifically driven by subjects' beliefs about what the community organizer believes about solar panels (that is, second-order beliefs), and demonstrate generalizability to four other highly non-normative behaviours. Our findings shed light on how to spread non-normative prosocial behaviours, offer an empirical demonstration of credibility-enhancing displays and have substantial implications for practitioners and policy-makers.}, } @article {pmid30356216, year = {2018}, author = {Ransom, RC and Carter, AC and Salhotra, A and Leavitt, T and Marecic, O and Murphy, MP and Lopez, ML and Wei, Y and Marshall, CD and Shen, EZ and Jones, RE and Sharir, A and Klein, OD and Chan, CKF and Wan, DC and Chang, HY and Longaker, MT}, title = {Mechanoresponsive stem cells acquire neural crest fate in jaw regeneration.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {514-521}, doi = {10.1038/s41586-018-0650-9}, pmid = {30356216}, issn = {1476-4687}, support = {R01 DE026730/DE/NIDCR NIH HHS/United States ; U24 DE026914/DE/NIDCR NIH HHS/United States ; K08 DE024269/DE/NIDCR NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; }, abstract = {During both embryonic development and adult tissue regeneration, changes in chromatin structure driven by master transcription factors lead to stimulus-responsive transcriptional programs. A thorough understanding of how stem cells in the skeleton interpret mechanical stimuli and enact regeneration would shed light on how forces are transduced to the nucleus in regenerative processes. Here we develop a genetically dissectible mouse model of mandibular distraction osteogenesis-which is a process that is used in humans to correct an undersized lower jaw that involves surgically separating the jaw bone, which elicits new bone growth in the gap. We use this model to show that regions of newly formed bone are clonally derived from stem cells that reside in the skeleton. Using chromatin and transcriptional profiling, we show that these stem-cell populations gain activity within the focal adhesion kinase (FAK) signalling pathway, and that inhibiting FAK abolishes new bone formation. Mechanotransduction via FAK in skeletal stem cells during distraction activates a gene-regulatory program and retrotransposons that are normally active in primitive neural crest cells, from which skeletal stem cells arise during development. This reversion to a developmental state underlies the robust tissue growth that facilitates stem-cell-based regeneration of adult skeletal tissue.}, } @article {pmid30356215, year = {2018}, author = {Schretter, CE and Vielmetter, J and Bartos, I and Marka, Z and Marka, S and Argade, S and Mazmanian, SK}, title = {A gut microbial factor modulates locomotor behaviour in Drosophila.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {402-406}, pmid = {30356215}, issn = {1476-4687}, support = {R01 NS085910/NS/NINDS NIH HHS/United States ; }, abstract = {While research into the biology of animal behaviour has primarily focused on the central nervous system, cues from peripheral tissues and the environment have been implicated in brain development and function1. There is emerging evidence that bidirectional communication between the gut and the brain affects behaviours including anxiety, cognition, nociception and social interaction1-9. Coordinated locomotor behaviour is critical for the survival and propagation of animals, and is regulated by internal and external sensory inputs10,11. However, little is known about how the gut microbiome influences host locomotion, or the molecular and cellular mechanisms involved. Here we report that germ-free status or antibiotic treatment results in hyperactive locomotor behaviour in the fruit fly Drosophila melanogaster. Increased walking speed and daily activity in the absence of a gut microbiome are rescued by mono-colonization with specific bacteria, including the fly commensal Lactobacillus brevis. The bacterial enzyme xylose isomerase from L. brevis recapitulates the locomotor effects of microbial colonization by modulating sugar metabolism in flies. Notably, thermogenetic activation of octopaminergic neurons or exogenous administration of octopamine, the invertebrate counterpart of noradrenaline, abrogates the effects of xylose isomerase on Drosophila locomotion. These findings reveal a previously unappreciated role for the gut microbiome in modulating locomotion, and identify octopaminergic neurons as mediators of peripheral microbial cues that regulate motor behaviour in animals.}, } @article {pmid30356214, year = {2018}, author = {Liu, H and Zhang, H and Wu, X and Ma, D and Wu, J and Wang, L and Jiang, Y and Fei, Y and Zhu, C and Tan, R and Jungblut, P and Pei, G and Dorhoi, A and Yan, Q and Zhang, F and Zheng, R and Liu, S and Liang, H and Liu, Z and Yang, H and Chen, J and Wang, P and Tang, T and Peng, W and Hu, Z and Xu, Z and Huang, X and Wang, J and Li, H and Zhou, Y and Liu, F and Yan, D and Kaufmann, SHE and Chen, C and Mao, Z and Ge, B}, title = {Nuclear cGAS suppresses DNA repair and promotes tumorigenesis.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {131-136}, doi = {10.1038/s41586-018-0629-6}, pmid = {30356214}, issn = {1476-4687}, mesh = {Active Transport, Cell Nucleus ; Adult ; Animals ; Cell Cycle Proteins/antagonists & inhibitors/metabolism ; Cell Line, Tumor ; Cell Nucleus/enzymology/*metabolism ; Cell Transformation, Neoplastic/*pathology ; DNA Breaks, Double-Stranded ; DNA Damage ; Female ; HEK293 Cells ; Humans ; Intracellular Signaling Peptides and Proteins/antagonists & inhibitors/metabolism ; Male ; Membrane Proteins/metabolism ; Mice ; Mice, Inbred C57BL ; Neoplasm Proteins/metabolism ; Neoplasms/genetics/*metabolism/*pathology ; Nucleotidyltransferases/deficiency/*metabolism ; Phosphorylation ; Phthalazines/pharmacology ; Piperazines/pharmacology ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors/metabolism ; Protein Binding/drug effects ; *Recombinational DNA Repair/genetics ; src-Family Kinases/metabolism ; }, abstract = {Accurate repair of DNA double-stranded breaks by homologous recombination preserves genome integrity and inhibits tumorigenesis. Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that activates innate immunity by initiating the STING-IRF3-type I IFN signalling cascade1,2. Recognition of ruptured micronuclei by cGAS links genome instability to the innate immune response3,4, but the potential involvement of cGAS in DNA repair remains unknown. Here we demonstrate that cGAS inhibits homologous recombination in mouse and human models. DNA damage induces nuclear translocation of cGAS in a manner that is dependent on importin-α, and the phosphorylation of cGAS at tyrosine 215-mediated by B-lymphoid tyrosine kinase-facilitates the cytosolic retention of cGAS. In the nucleus, cGAS is recruited to double-stranded breaks and interacts with PARP1 via poly(ADP-ribose). The cGAS-PARP1 interaction impedes the formation of the PARP1-Timeless complex, and thereby suppresses homologous recombination. We show that knockdown of cGAS suppresses DNA damage and inhibits tumour growth both in vitro and in vivo. We conclude that nuclear cGAS suppresses homologous-recombination-mediated repair and promotes tumour growth, and that cGAS therefore represents a potential target for cancer prevention and therapy.}, } @article {pmid30356213, year = {2018}, author = {Bilyard, MK and Bailey, HJ and Raich, L and Gafitescu, MA and Machida, T and Iglésias-Fernández, J and Lee, SS and Spicer, CD and Rovira, C and Yue, WW and Davis, BG}, title = {Palladium-mediated enzyme activation suggests multiphase initiation of glycogenesis.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {235-240}, doi = {10.1038/s41586-018-0644-7}, pmid = {30356213}, issn = {1476-4687}, support = {092809/Z/10/Z//Wellcome Trust/United Kingdom ; }, abstract = {Biosynthesis of glycogen, the essential glucose (and hence energy) storage molecule in humans, animals and fungi1, is initiated by the glycosyltransferase enzyme, glycogenin (GYG). Deficiencies in glycogen formation cause neurodegenerative and metabolic disease2-4, and mouse knockout5 and inherited human mutations6 of GYG impair glycogen synthesis. GYG acts as a 'seed core' for the formation of the glycogen particle by catalysing its own stepwise autoglucosylation to form a covalently bound gluco-oligosaccharide chain at initiation site Tyr 195. Precise mechanistic studies have so far been prevented by an inability to access homogeneous glycoforms of this protein, which unusually acts as both catalyst and substrate. Here we show that unprecedented direct access to different, homogeneously glucosylated states of GYG can be accomplished through a palladium-mediated enzyme activation 'shunt' process using on-protein C-C bond formation. Careful mimicry of GYG intermediates recapitulates catalytic activity at distinct stages, which in turn allows discovery of triphasic kinetics and substrate plasticity in GYG's use of sugar substrates. This reveals a tolerant but 'proof-read' mechanism that underlies the precision of this metabolic process. The present demonstration of direct, chemically controlled access to intermediate states of active enzymes suggests that such ligation-dependent activation could be a powerful tool in the study of mechanism.}, } @article {pmid30356212, year = {2018}, author = {Curtin, NA and Bartlam-Brooks, HLA and Hubel, TY and Lowe, JC and Gardner-Medwin, AR and Bennitt, E and Amos, SJ and Lorenc, M and West, TG and Wilson, AM}, title = {Remarkable muscles, remarkable locomotion in desert-dwelling wildebeest.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {393-396}, doi = {10.1038/s41586-018-0602-4}, pmid = {30356212}, issn = {1476-4687}, abstract = {Large mammals that live in arid and/or desert environments can cope with seasonal and local variations in rainfall, food and climate1 by moving long distances, often without reliable water or food en route. The capacity of an animal for this long-distance travel is substantially dependent on the rate of energy utilization and thus heat production during locomotion-the cost of transport2-4. The terrestrial cost of transport is much higher than for flying (7.5 times) and swimming (20 times)4. Terrestrial migrants are usually large1-3 with anatomical specializations for economical locomotion5-9, because the cost of transport reduces with increasing size and limb length5-7. Here we used GPS-tracking collars10 with movement and environmental sensors to show that blue wildebeest (Connochaetes taurinus, 220 kg) that live in a hot arid environment in Northern Botswana walked up to 80 km over five days without drinking. They predominantly travelled during the day and locomotion appeared to be unaffected by temperature and humidity, although some behavioural thermoregulation was apparent. We measured power and efficiency of work production (mechanical work and heat production) during cyclic contractions of intact muscle biopsies from the forelimb flexor carpi ulnaris of wildebeest and domestic cows (Bos taurus, 760 kg), a comparable but relatively sedentary ruminant. The energetic costs of isometric contraction (activation and force generation) in wildebeest and cows were similar to published values for smaller mammals. Wildebeest muscle was substantially more efficient (62.6%) than the same muscle from much larger cows (41.8%) and comparable measurements that were obtained from smaller mammals (mouse (34%)11 and rabbit (27%)). We used the direct energetic measurements on intact muscle fibres to model the contribution of high working efficiency of wildebeest muscle to minimizing thermoregulatory challenges during their long migrations under hot arid conditions.}, } @article {pmid30356211, year = {2018}, author = {Awad, E and Dsouza, S and Kim, R and Schulz, J and Henrich, J and Shariff, A and Bonnefon, JF and Rahwan, I}, title = {The Moral Machine experiment.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {59-64}, doi = {10.1038/s41586-018-0637-6}, pmid = {30356211}, issn = {1476-4687}, abstract = {With the rapid development of artificial intelligence have come concerns about how machines will make moral decisions, and the major challenge of quantifying societal expectations about the ethical principles that should guide machine behaviour. To address this challenge, we deployed the Moral Machine, an online experimental platform designed to explore the moral dilemmas faced by autonomous vehicles. This platform gathered 40 million decisions in ten languages from millions of people in 233 countries and territories. Here we describe the results of this experiment. First, we summarize global moral preferences. Second, we document individual variations in preferences, based on respondents' demographics. Third, we report cross-cultural ethical variation, and uncover three major clusters of countries. Fourth, we show that these differences correlate with modern institutions and deep cultural traits. We discuss how these preferences can contribute to developing global, socially acceptable principles for machine ethics. All data used in this article are publicly available.}, } @article {pmid30356210, year = {2018}, author = {Malapit, CA and Bour, JR and Brigham, CE and Sanford, MS}, title = {Base-free nickel-catalysed decarbonylative Suzuki-Miyaura coupling of acid fluorides.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {100-104}, pmid = {30356210}, issn = {1476-4687}, support = {R01 GM073836/GM/NIGMS NIH HHS/United States ; }, mesh = {Boronic Acids/*chemistry ; Carboxylic Acids/*chemistry ; Catalysis ; Fluorides/*chemistry ; Indicators and Reagents/chemistry ; Nickel/*chemistry ; }, abstract = {The Suzuki-Miyaura cross-coupling of organoboron nucleophiles with aryl halide electrophiles is one of the most widely used carbon-carbon bond-forming reactions in organic and medicinal chemistry1,2. A key challenge associated with these transformations is that they generally require the addition of an exogenous base, the role of which is to enable transmetallation between the organoboron nucleophile and the metal catalyst3. This requirement limits the substrate scope of the reaction because the added base promotes competitive decomposition of many organoboron substrates3-5. As such, considerable research has focused on strategies for mitigating base-mediated side reactions6-12. Previous efforts have primarily focused either on designing strategically masked organoboron reagents (to slow base-mediated decomposition)6-8 or on developing highly active palladium precatalysts (to accelerate cross-coupling relative to base-mediated decomposition pathways)10-12. An attractive alternative approach involves identifying combinations of catalyst and electrophile that enable Suzuki-Miyaura-type reactions to proceed without an exogenous base12-14. Here we use this approach to develop a nickel-catalysed coupling of aryl boronic acids with acid fluorides15-17, which are formed in situ from readily available carboxylic acids18-22. This combination of catalyst and electrophile enables a mechanistic manifold in which a 'transmetallation-active' aryl nickel fluoride intermediate is generated directly in the catalytic cycle13,16. As such, this transformation does not require an exogenous base and is applicable to a wide range of base-sensitive boronic acids and biologically active carboxylic acids.}, } @article {pmid30356205, year = {2018}, author = {Larivière, V and Sugimoto, CR}, title = {Do authors comply when funders enforce open access to research?.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {483-486}, doi = {10.1038/d41586-018-07101-w}, pmid = {30356205}, issn = {1476-4687}, } @article {pmid30356204, year = {2018}, author = {Gibney, E}, title = {How to build a Moon base.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {474-478}, doi = {10.1038/d41586-018-07107-4}, pmid = {30356204}, issn = {1476-4687}, } @article {pmid30356203, year = {2018}, author = {Woolston, C}, title = {Satisfaction in science.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {611-614}, doi = {10.1038/d41586-018-07111-8}, pmid = {30356203}, issn = {1476-4687}, } @article {pmid30356202, year = {2018}, author = {Bajak, A}, title = {Meet the zoologist who discovered a new species in his native Colombia.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {S111}, doi = {10.1038/d41586-018-07114-5}, pmid = {30356202}, issn = {1476-4687}, } @article {pmid30356201, year = {2018}, author = {Bajak, A}, title = {Science in Colombia on the cusp of change.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {S109-S111}, doi = {10.1038/d41586-018-07113-6}, pmid = {30356201}, issn = {1476-4687}, } @article {pmid30356200, year = {2018}, author = {Holmes, J}, title = {Rebels of art and science: the empirical drive of the Pre-Raphaelites.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {490-491}, doi = {10.1038/d41586-018-07110-9}, pmid = {30356200}, issn = {1476-4687}, } @article {pmid30356199, year = {2018}, author = {}, title = {Medical chimps' retirement, Nobel laureates' Brexit warning and science mega-prizes.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {464-465}, doi = {10.1038/d41586-018-07105-6}, pmid = {30356199}, issn = {1476-4687}, } @article {pmid30356198, year = {2018}, author = {}, title = {Matters Arising: a venue for scientific comments.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {460}, doi = {10.1038/d41586-018-07150-1}, pmid = {30356198}, issn = {1476-4687}, } @article {pmid30356197, year = {2018}, author = {Maxmen, A}, title = {Self-driving car dilemmas reveal that moral choices are not universal.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {469-470}, doi = {10.1038/d41586-018-07135-0}, pmid = {30356197}, issn = {1476-4687}, } @article {pmid30356195, year = {2018}, author = {Mahmoudi, M}, title = {Improve reporting systems for academic bullying.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {494}, doi = {10.1038/d41586-018-07154-x}, pmid = {30356195}, issn = {1476-4687}, } @article {pmid30356194, year = {2018}, author = {Bubb, S and Cowan, K and Fiennes, C}, title = {Co-production to help charities and donors prioritize research topics.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {494}, doi = {10.1038/d41586-018-07145-y}, pmid = {30356194}, issn = {1476-4687}, } @article {pmid30356193, year = {2018}, author = {Calow, P}, title = {Co-producers help frame research questions, not answers.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {494}, doi = {10.1038/d41586-018-07155-w}, pmid = {30356193}, issn = {1476-4687}, } @article {pmid30356192, year = {2018}, author = {Baskin, TI}, title = {Keep authorship for writers.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {494}, doi = {10.1038/d41586-018-07156-9}, pmid = {30356192}, issn = {1476-4687}, } @article {pmid30356191, year = {2018}, author = {Holbrook, JB and Curry, S and Kamerlin, SCL}, title = {Debate on academic freedom and open access is healthy.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {494}, doi = {10.1038/d41586-018-07153-y}, pmid = {30356191}, issn = {1476-4687}, } @article {pmid30356190, year = {2018}, author = {Measey, J}, title = {Europe's plan S could raise everyone else's publication paywall.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {494}, doi = {10.1038/d41586-018-07152-z}, pmid = {30356190}, issn = {1476-4687}, } @article {pmid30356189, year = {2018}, author = {Folland, TG and Caldwell, JD}, title = {Precise control of infrared polarization using crystal vibrations.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {499-501}, doi = {10.1038/d41586-018-07087-5}, pmid = {30356189}, issn = {1476-4687}, } @article {pmid30356188, year = {2018}, author = {Serenelli, A}, title = {Solar neutrinos reveal how the Sun shines.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {496-497}, doi = {10.1038/d41586-018-07099-1}, pmid = {30356188}, issn = {1476-4687}, } @article {pmid30356187, year = {2018}, author = {Stewart, CJ and Ajami, NJ and O'Brien, JL and Hutchinson, DS and Smith, DP and Wong, MC and Ross, MC and Lloyd, RE and Doddapaneni, H and Metcalf, GA and Muzny, D and Gibbs, RA and Vatanen, T and Huttenhower, C and Xavier, RJ and Rewers, M and Hagopian, W and Toppari, J and Ziegler, AG and She, JX and Akolkar, B and Lernmark, A and Hyoty, H and Vehik, K and Krischer, JP and Petrosino, JF}, title = {Temporal development of the gut microbiome in early childhood from the TEDDY study.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {583-588}, doi = {10.1038/s41586-018-0617-x}, pmid = {30356187}, issn = {1476-4687}, support = {U01 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK063865/DK/NIDDK NIH HHS/United States ; UC4 DK063863/DK/NIDDK NIH HHS/United States ; U01 DK063836/DK/NIDDK NIH HHS/United States ; UC4 DK112243/DK/NIDDK NIH HHS/United States ; U01 DK063829/DK/NIDDK NIH HHS/United States ; UC4 DK095300/DK/NIDDK NIH HHS/United States ; U01 DK063865/DK/NIDDK NIH HHS/United States ; UC4 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK063829/DK/NIDDK NIH HHS/United States ; HHSN267200700014C/LM/NLM NIH HHS/United States ; UC4 DK063821/DK/NIDDK NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; UC4 DK063836/DK/NIDDK NIH HHS/United States ; HHSN267200700014C/DK/NIDDK NIH HHS/United States ; U01 DK063861/DK/NIDDK NIH HHS/United States ; U01 DK063863/DK/NIDDK NIH HHS/United States ; U01 DK063790/DK/NIDDK NIH HHS/United States ; UL1 TR000064/TR/NCATS NIH HHS/United States ; UC4 DK106955/DK/NIDDK NIH HHS/United States ; UC4 DK100238/DK/NIDDK NIH HHS/United States ; UC4 DK117483/DK/NIDDK NIH HHS/United States ; }, abstract = {The development of the microbiome from infancy to childhood is dependent on a range of factors, with microbial-immune crosstalk during this time thought to be involved in the pathobiology of later life diseases1-9 such as persistent islet autoimmunity and type 1 diabetes10-12. However, to our knowledge, no studies have performed extensive characterization of the microbiome in early life in a large, multi-centre population. Here we analyse longitudinal stool samples from 903 children between 3 and 46 months of age by 16S rRNA gene sequencing (n = 12,005) and metagenomic sequencing (n = 10,867), as part of the The Environmental Determinants of Diabetes in the Young (TEDDY) study. We show that the developing gut microbiome undergoes three distinct phases of microbiome progression: a developmental phase (months 3-14), a transitional phase (months 15-30), and a stable phase (months 31-46). Receipt of breast milk, either exclusive or partial, was the most significant factor associated with the microbiome structure. Breastfeeding was associated with higher levels of Bifidobacterium species (B. breve and B. bifidum), and the cessation of breast milk resulted in faster maturation of the gut microbiome, as marked by the phylum Firmicutes. Birth mode was also significantly associated with the microbiome during the developmental phase, driven by higher levels of Bacteroides species (particularly B. fragilis) in infants delivered vaginally. Bacteroides was also associated with increased gut diversity and faster maturation, regardless of the birth mode. Environmental factors including geographical location and household exposures (such as siblings and furry pets) also represented important covariates. A nested case-control analysis revealed subtle associations between microbial taxonomy and the development of islet autoimmunity or type 1 diabetes. These data determine the structural and functional assembly of the microbiome in early life and provide a foundation for targeted mechanistic investigation into the consequences of microbial-immune crosstalk for long-term health.}, } @article {pmid30356186, year = {2018}, author = {, }, title = {Comprehensive measurement of pp-chain solar neutrinos.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {505-510}, doi = {10.1038/s41586-018-0624-y}, pmid = {30356186}, issn = {1476-4687}, abstract = {About 99 per cent of solar energy is produced through sequences of nuclear reactions that convert hydrogen into helium, starting from the fusion of two protons (the pp chain). The neutrinos emitted by five of these reactions represent a unique probe of the Sun's internal working and, at the same time, offer an intense natural neutrino beam for fundamental physics. Here we report a complete study of the pp chain. We measure the neutrino-electron elastic-scattering rates for neutrinos produced by four reactions of the chain: the initial proton-proton fusion, the electron-capture decay of beryllium-7, the three-body proton-electron-proton (pep) fusion, here measured with the highest precision so far achieved, and the boron-8 beta decay, measured with the lowest energy threshold. We also set a limit on the neutrino flux produced by the 3He-proton fusion (hep). These measurements provide a direct determination of the relative intensity of the two primary terminations of the pp chain (pp-I and pp-II) and an indication that the temperature profile in the Sun is more compatible with solar models that assume high surface metallicity. We also determine the survival probability of solar electron neutrinos at different energies, thus probing simultaneously and with high precision the neutrino flavour-conversion paradigm, both in vacuum and in matter-dominated regimes.}, } @article {pmid30356185, year = {2018}, author = {Ma, W and Alonso-González, P and Li, S and Nikitin, AY and Yuan, J and Martín-Sánchez, J and Taboada-Gutiérrez, J and Amenabar, I and Li, P and Vélez, S and Tollan, C and Dai, Z and Zhang, Y and Sriram, S and Kalantar-Zadeh, K and Lee, ST and Hillenbrand, R and Bao, Q}, title = {In-plane anisotropic and ultra-low-loss polaritons in a natural van der Waals crystal.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {557-562}, doi = {10.1038/s41586-018-0618-9}, pmid = {30356185}, issn = {1476-4687}, abstract = {Polaritons-hybrid light-matter excitations-enable nanoscale control of light. Particularly large polariton field confinement and long lifetimes can be found in graphene and materials consisting of two-dimensional layers bound by weak van der Waals forces1,2 (vdW materials). These polaritons can be tuned by electric fields3,4 or by material thickness5, leading to applications including nanolasers6, tunable infrared and terahertz detectors7, and molecular sensors8. Polaritons with anisotropic propagation along the surface of vdW materials have been predicted, caused by in-plane anisotropic structural and electronic properties9. In such materials, elliptic and hyperbolic in-plane polariton dispersion can be expected (for example, plasmon polaritons in black phosphorus9), the latter leading to an enhanced density of optical states and ray-like directional propagation along the surface. However, observation of anisotropic polariton propagation in natural materials has so far remained elusive. Here we report anisotropic polariton propagation along the surface of α-MoO3, a natural vdW material. By infrared nano-imaging and nano-spectroscopy of semiconducting α-MoO3 flakes and disks, we visualize and verify phonon polaritons with elliptic and hyperbolic in-plane dispersion, and with wavelengths (up to 60 times smaller than the corresponding photon wavelengths) comparable to those of graphene plasmon polaritons and boron nitride phonon polaritons3-5. From signal oscillations in real-space images we measure polariton amplitude lifetimes of 8 picoseconds, which is more than ten times larger than that of graphene plasmon polaritons at room temperature10. They are also a factor of about four larger than the best values so far reported for phonon polaritons in isotopically engineered boron nitride11 and for graphene plasmon polaritons at low temperatures12. In-plane anisotropic and ultra-low-loss polaritons in vdW materials could enable directional and strong light-matter interactions, nanoscale directional energy transfer and integrated flat optics in applications ranging from bio-sensing to quantum nanophotonics.}, } @article {pmid30356184, year = {2018}, author = {Riller, U and Poelchau, MH and Rae, ASP and Schulte, FM and Collins, GS and Melosh, HJ and Grieve, RAF and Morgan, JV and Gulick, SPS and Lofi, J and Diaw, A and McCall, N and Kring, DA and , }, title = {Rock fluidization during peak-ring formation of large impact structures.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {511-518}, doi = {10.1038/s41586-018-0607-z}, pmid = {30356184}, issn = {1476-4687}, support = {OCE-1737351//National Science Foundation/International ; OCE-1450528//National Science Foundation/International ; OCE-1736826//National Science Foundation/International ; }, abstract = {Large meteorite impact structures on the terrestrial bodies of the Solar System contain pronounced topographic rings, which emerged from uplifted target (crustal) rocks within minutes of impact. To flow rapidly over large distances, these target rocks must have weakened drastically, but they subsequently regained sufficient strength to build and sustain topographic rings. The mechanisms of rock deformation that accomplish such extreme change in mechanical behaviour during cratering are largely unknown and have been debated for decades. Recent drilling of the approximately 200-km-diameter Chicxulub impact structure in Mexico has produced a record of brittle and viscous deformation within its peak-ring rocks. Here we show how catastrophic rock weakening upon impact is followed by an increase in rock strength that culminated in the formation of the peak ring during cratering. The observations point to quasi-continuous rock flow and hence acoustic fluidization as the dominant physical process controlling initial cratering, followed by increasingly localized faulting.}, } @article {pmid30356183, year = {2018}, author = {Vatanen, T and Franzosa, EA and Schwager, R and Tripathi, S and Arthur, TD and Vehik, K and Lernmark, Å and Hagopian, WA and Rewers, MJ and She, JX and Toppari, J and Ziegler, AG and Akolkar, B and Krischer, JP and Stewart, CJ and Ajami, NJ and Petrosino, JF and Gevers, D and Lähdesmäki, H and Vlamakis, H and Huttenhower, C and Xavier, RJ}, title = {The human gut microbiome in early-onset type 1 diabetes from the TEDDY study.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {589-594}, doi = {10.1038/s41586-018-0620-2}, pmid = {30356183}, issn = {1476-4687}, support = {U01 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK063863/DK/NIDDK NIH HHS/United States ; UL1 TR000064/TR/NCATS NIH HHS/United States ; U01 DK063836/DK/NIDDK NIH HHS/United States ; U01 DK063829/DK/NIDDK NIH HHS/United States ; U01 DK063865/DK/NIDDK NIH HHS/United States ; UC4 DK095300/DK/NIDDK NIH HHS/United States ; UC4 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK063829/DK/NIDDK NIH HHS/United States ; UC4 DK063821/DK/NIDDK NIH HHS/United States ; UC4 DK117483/DK/NIDDK NIH HHS/United States ; UC4 DK063836/DK/NIDDK NIH HHS/United States ; UC4 DK112243/DK/NIDDK NIH HHS/United States ; HHSN267200700014C/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; U01 DK063861/DK/NIDDK NIH HHS/United States ; UC4 DK063865/DK/NIDDK NIH HHS/United States ; U01 DK063863/DK/NIDDK NIH HHS/United States ; U01 DK063790/DK/NIDDK NIH HHS/United States ; UC4 DK106955/DK/NIDDK NIH HHS/United States ; UC4 DK100238/DK/NIDDK NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R24 DK110499/DK/NIDDK NIH HHS/United States ; }, abstract = {Type 1 diabetes (T1D) is an autoimmune disease that targets pancreatic islet beta cells and incorporates genetic and environmental factors1, including complex genetic elements2, patient exposures3 and the gut microbiome4. Viral infections5 and broader gut dysbioses6 have been identified as potential causes or contributing factors; however, human studies have not yet identified microbial compositional or functional triggers that are predictive of islet autoimmunity or T1D. Here we analyse 10,913 metagenomes in stool samples from 783 mostly white, non-Hispanic children. The samples were collected monthly from three months of age until the clinical end point (islet autoimmunity or T1D) in the The Environmental Determinants of Diabetes in the Young (TEDDY) study, to characterize the natural history of the early gut microbiome in connection to islet autoimmunity, T1D diagnosis, and other common early life events such as antibiotic treatments and probiotics. The microbiomes of control children contained more genes that were related to fermentation and the biosynthesis of short-chain fatty acids, but these were not consistently associated with particular taxa across geographically diverse clinical centres, suggesting that microbial factors associated with T1D are taxonomically diffuse but functionally more coherent. When we investigated the broader establishment and development of the infant microbiome, both taxonomic and functional profiles were dynamic and highly individualized, and dominated in the first year of life by one of three largely exclusive Bifidobacterium species (B. bifidum, B. breve or B. longum) or by the phylum Proteobacteria. In particular, the strain-specific carriage of genes for the utilization of human milk oligosaccharide within a subset of B. longum was present specifically in breast-fed infants. These analyses of TEDDY gut metagenomes provide, to our knowledge, the largest and most detailed longitudinal functional profile of the developing gut microbiome in relation to islet autoimmunity, T1D and other early childhood events. Together with existing evidence from human cohorts7,8 and a T1D mouse model9, these data support the protective effects of short-chain fatty acids in early-onset human T1D.}, } @article {pmid30356182, year = {2018}, author = {Rae, JWB and Burke, A and Robinson, LF and Adkins, JF and Chen, T and Cole, C and Greenop, R and Li, T and Littley, EFM and Nita, DC and Stewart, JA and Taylor, BJ}, title = {CO2 storage and release in the deep Southern Ocean on millennial to centennial timescales.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {569-573}, doi = {10.1038/s41586-018-0614-0}, pmid = {30356182}, issn = {1476-4687}, abstract = {The cause of changes in atmospheric carbon dioxide (CO2) during the recent ice ages is yet to be fully explained. Most mechanisms for glacial-interglacial CO2 change have centred on carbon exchange with the deep ocean, owing to its large size and relatively rapid exchange with the atmosphere1. The Southern Ocean is thought to have a key role in this exchange, as much of the deep ocean is ventilated to the atmosphere in this region2. However, it is difficult to reconstruct changes in deep Southern Ocean carbon storage, so few direct tests of this hypothesis have been carried out. Here we present deep-sea coral boron isotope data that track the pH-and thus the CO2 chemistry-of the deep Southern Ocean over the past forty thousand years. At sites closest to the Antarctic continental margin, and most influenced by the deep southern waters that form the ocean's lower overturning cell, we find a close relationship between ocean pH and atmospheric CO2: during intervals of low CO2, ocean pH is low, reflecting enhanced ocean carbon storage; and during intervals of rising CO2, ocean pH rises, reflecting loss of carbon from the ocean to the atmosphere. Correspondingly, at shallower sites we find rapid (millennial- to centennial-scale) decreases in pH during abrupt increases in CO2, reflecting the rapid transfer of carbon from the deep ocean to the upper ocean and atmosphere. Our findings confirm the importance of the deep Southern Ocean in ice-age CO2 change, and show that deep-ocean CO2 release can occur as a dynamic feedback to rapid climate change on centennial timescales.}, } @article {pmid30356154, year = {2018}, author = {Solden, LM and Naas, AE and Roux, S and Daly, RA and Collins, WB and Nicora, CD and Purvine, SO and Hoyt, DW and Schückel, J and Jørgensen, B and Willats, W and Spalinger, DE and Firkins, JL and Lipton, MS and Sullivan, MB and Pope, PB and Wrighton, KC}, title = {Interspecies cross-feeding orchestrates carbon degradation in the rumen ecosystem.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1274-1284}, doi = {10.1038/s41564-018-0225-4}, pmid = {30356154}, issn = {2058-5276}, abstract = {Because of their agricultural value, there is a great body of research dedicated to understanding the microorganisms responsible for rumen carbon degradation. However, we lack a holistic view of the microbial food web responsible for carbon processing in this ecosystem. Here, we sampled rumen-fistulated moose, allowing access to rumen microbial communities actively degrading woody plant biomass in real time. We resolved 1,193 viral contigs and 77 unique, near-complete microbial metagenome-assembled genomes, many of which lacked previous metabolic insights. Plant-derived metabolites were measured with NMR and carbohydrate microarrays to quantify the carbon nutrient landscape. Network analyses directly linked measured metabolites to expressed proteins from these unique metagenome-assembled genomes, revealing a genome-resolved three-tiered carbohydrate-fuelled trophic system. This provided a glimpse into microbial specialization into functional guilds defined by specific metabolites. To validate our proteomic inferences, the catalytic activity of a polysaccharide utilization locus from a highly connected metabolic hub genome was confirmed using heterologous gene expression. Viral detected proteins and linkages to microbial hosts demonstrated that phage are active controllers of rumen ecosystem function. Our findings elucidate the microbial and viral members, as well as their metabolic interdependencies, that support in situ carbon degradation in the rumen ecosystem.}, } @article {pmid30356153, year = {2018}, author = {}, title = {We need to talk about crapping.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1189}, doi = {10.1038/s41564-018-0287-3}, pmid = {30356153}, issn = {2058-5276}, } @article {pmid30356152, year = {2018}, author = {Cohen, SB and Urdahl, KB}, title = {Going beyond gamma for TB protection.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1194-1195}, doi = {10.1038/s41564-018-0266-8}, pmid = {30356152}, issn = {2058-5276}, } @article {pmid30356151, year = {2018}, author = {Riedl, W and Gack, MU}, title = {Dusting for flu's fingerprints.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1196-1197}, doi = {10.1038/s41564-018-0270-z}, pmid = {30356151}, issn = {2058-5276}, } @article {pmid30356150, year = {2018}, author = {Francetic, O}, title = {Tagging the type VI secretion system.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1190-1191}, doi = {10.1038/s41564-018-0277-5}, pmid = {30356150}, issn = {2058-5276}, } @article {pmid30356149, year = {2018}, author = {Economou, A}, title = {Breaching the wall.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1192-1193}, doi = {10.1038/s41564-018-0279-3}, pmid = {30356149}, issn = {2058-5276}, } @article {pmid30355772, year = {2018}, author = {Raugei, S and Seefeldt, LC and Hoffman, BM}, title = {Critical computational analysis illuminates the reductive-elimination mechanism that activates nitrogenase for N2 reduction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10521-E10530}, pmid = {30355772}, issn = {1091-6490}, support = {R01 GM111097/GM/NIGMS NIH HHS/United States ; }, abstract = {Recent spectroscopic, kinetic, photophysical, and thermodynamic measurements show activation of nitrogenase for N2 → 2NH3 reduction involves the reductive elimination (re) of H2 from two [Fe-H-Fe] bridging hydrides bound to the catalytic [7Fe-9S-Mo-C-homocitrate] FeMo-cofactor (FeMo-co). These studies rationalize the Lowe-Thorneley kinetic scheme's proposal of mechanistically obligatory formation of one H2 for each N2 reduced. They also provide an overall framework for understanding the mechanism of nitrogen fixation by nitrogenase. However, they directly pose fundamental questions addressed computationally here. We here report an extensive computational investigation of the structure and energetics of possible nitrogenase intermediates using structural models for the active site with a broad range in complexity, while evaluating a diverse set of density functional theory flavors. (i) This shows that to prevent spurious disruption of FeMo-co having accumulated 4[e-/H+] it is necessary to include: all residues (and water molecules) interacting directly with FeMo-co via specific H-bond interactions; nonspecific local electrostatic interactions; and steric confinement. (ii) These calculations indicate an important role of sulfide hemilability in the overall conversion of E0 to a diazene-level intermediate. (iii) Perhaps most importantly, they explain (iiia) how the enzyme mechanistically couples exothermic H2 formation to endothermic cleavage of the N≡N triple bond in a nearly thermoneutral re/oxidative-addition equilibrium, (iiib) while preventing the "futile" generation of two H2 without N2 reduction: hydride re generates an H2 complex, but H2 is only lost when displaced by N2, to form an end-on N2 complex that proceeds to a diazene-level intermediate.}, } @article {pmid30355771, year = {2018}, author = {Liu, G and Jin, S and Hu, Y and Jiang, Q}, title = {Disease status affects the association between rs4813620 and the expression of Alzheimer's disease susceptibility gene TRIB3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10519-E10520}, pmid = {30355771}, issn = {1091-6490}, } @article {pmid30355770, year = {2018}, author = {Sanchez, AM and Shuman, S and Schwer, B}, title = {RNA polymerase II CTD interactome with 3' processing and termination factors in fission yeast and its impact on phosphate homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10652-E10661}, pmid = {30355770}, issn = {1091-6490}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 GM052470/GM/NIGMS NIH HHS/United States ; R35 GM126945/GM/NIGMS NIH HHS/United States ; }, abstract = {The carboxy-terminal domain (CTD) code encrypted within the Y1S2P3T4S5P6S7 heptad repeats of RNA polymerase II (Pol2) is deeply rooted in eukaryal biology. Key steps to deciphering the code are identifying the events in gene expression that are governed by individual "letters" and then defining a vocabulary of multiletter "words" and their meaning. Thr4 and Ser7 exert opposite effects on the fission yeast pho1 gene, expression of which is repressed under phosphate-replete conditions by transcription of an upstream flanking long noncoding RNA (lncRNA). Here we attribute the derepression of pho1 by a CTD-S7A mutation to precocious termination of lncRNA synthesis, an effect that is erased by mutations of cleavage-polyadenylation factor (CPF) subunits Ctf1, Ssu72, Ppn1, Swd22, and Dis2 and termination factor Rhn1. By contrast, a CTD-T4A mutation hyperrepresses pho1, as do CPF subunit and Rhn1 mutations, implying that T4A reduces lncRNA termination. Moreover, CTD-T4A is synthetically lethal with ppn1∆ and swd22∆, signifying that Thr4 and the Ppn1•Swd22 module play important, functionally redundant roles in promoting Pol2 termination. We find that Ppn1 and Swd22 become essential for viability when the CTD array is curtailed and that S7A overcomes the need for Ppn1•Swd22 in the short CTD context. Mutational synergies highlight redundant essential functions of (i) Ppn1•Swd22 and Rhn1, (ii) Ppn1•Swd22 and Ctf1, and (iii) Ssu72 and Dis2 phosphatases. CTD alleles Y1F, S2A, and T4A have overlapping synthetic lethalities with ppn1∆ and swd22∆, suggesting that Tyr1-Ser2-Thr4 form a three-letter CTD word that abets termination, with Rhn1 being a likely "reader" of this word.}, } @article {pmid30355769, year = {2018}, author = {Guo, L and Cesari, S and de Guillen, K and Chalvon, V and Mammri, L and Ma, M and Meusnier, I and Bonnot, F and Padilla, A and Peng, YL and Liu, J and Kroj, T}, title = {Specific recognition of two MAX effectors by integrated HMA domains in plant immune receptors involves distinct binding surfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11637-11642}, pmid = {30355769}, issn = {1091-6490}, abstract = {The structurally conserved but sequence-unrelated MAX (Magnaporthe oryzae avirulence and ToxB-like) effectors AVR1-CO39 and AVR-PikD from the blast fungus M. oryzae are recognized by the rice nucleotide-binding domain and leucine-rich repeat proteins (NLRs) RGA5 and Pikp-1, respectively. This involves, in both cases, direct interaction of the effector with a heavy metal-associated (HMA) integrated domain (ID) in the NLR. Here, we solved the crystal structures of a C-terminal fragment of RGA5 carrying the HMA ID (RGA5_S), alone, and in complex with AVR1-CO39 and compared it to the structure of the Pikp1HMA/AVR-PikD complex. In both complexes, HMA ID/MAX effector interactions involve antiparallel alignment of β-sheets from each partner. However, effector-binding occurs at different surfaces in Pikp1HMA and RGA5HMA, indicating that these interactions evolved independently by convergence of these two MAX effectors to the same type of plant target proteins. Interestingly, the effector-binding surface in RGA5HMA overlaps with the surface that mediates RGA5HMA self-interaction. Mutations in the HMA-binding interface of AVR1-CO39 perturb RGA5HMA-binding, in vitro and in vivo, and affect the recognition of M. oryzae in a rice cultivar containing Pi-CO39 Our study provides detailed insight into the mechanisms of effector recognition by NLRs, which has substantial implications for future engineering of NLRs to expand their recognition specificities. In addition, we propose, as a hypothesis for the understanding of effector diversity, that in the structurally conserved MAX effectors the molecular mechanism of host target protein-binding is conserved rather than the host target proteins themselves.}, } @article {pmid30355768, year = {2018}, author = {Segawa, K and Yanagihashi, Y and Yamada, K and Suzuki, C and Uchiyama, Y and Nagata, S}, title = {Phospholipid flippases enable precursor B cells to flee engulfment by macrophages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {48}, pages = {12212-12217}, pmid = {30355768}, issn = {1091-6490}, abstract = {ATP11A and ATP11C, members of the P4-ATPases, are flippases that translocate phosphatidylserine (PtdSer) from the outer to inner leaflet of the plasma membrane. Using the W3 T lymphoma cell line, we found that Ca2+ ionophore-induced phospholipid scrambling caused prolonged PtdSer exposure in cells lacking both the ATP11A and ATP11C genes. ATP11C-null (ATP11C-/y) mutant mice exhibit severe B-cell deficiency. In wild-type mice, ATP11C was expressed at all B-cell developmental stages, while ATP11A was not expressed after pro-B-cell stages, indicating that ATP11C-/y early B-cell progenitors lacked plasma membrane flippases. The receptor kinases MerTK and Axl are known to be essential for the PtdSer-mediated engulfment of apoptotic cells by macrophages. MerTK-/- and Axl-/- double deficiency fully rescued the lymphopenia in the ATP11C-/y bone marrow. Many of the rescued ATP11C-/y pre-B and immature B cells exposed PtdSer, and these cells were engulfed alive by wild-type peritoneal macrophages, in a PtdSer-dependent manner. These results indicate that ATP11A and ATP11C in precursor B cells are essential for rapidly internalizing PtdSer from the cell surface to prevent the cells' engulfment by macrophages.}, } @article {pmid30355767, year = {2018}, author = {Chen, X and Liu, D and Zhou, D and Si, Y and Xu, D and Stamatkin, CW and Ghozayel, MK and Ripsch, MS and Obukhov, AG and White, FA and Meroueh, SO}, title = {Small-molecule CaVα1⋅CaVβ antagonist suppresses neuronal voltage-gated calcium-channel trafficking.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10566-E10575}, pmid = {30355767}, issn = {1091-6490}, support = {I01 BX002209/BX/BLRD VA/United States ; R01 HL115140/HL/NHLBI NIH HHS/United States ; }, abstract = {Extracellular calcium flow through neuronal voltage-gated CaV2.2 calcium channels converts action potential-encoded information to the release of pronociceptive neurotransmitters in the dorsal horn of the spinal cord, culminating in excitation of the postsynaptic central nociceptive neurons. The CaV2.2 channel is composed of a pore-forming α1 subunit (CaVα1) that is engaged in protein-protein interactions with auxiliary α2/δ and β subunits. The high-affinity CaV2.2α1⋅CaVβ3 protein-protein interaction is essential for proper trafficking of CaV2.2 channels to the plasma membrane. Here, structure-based computational screening led to small molecules that disrupt the CaV2.2α1⋅CaVβ3 protein-protein interaction. The binding mode of these compounds reveals that three substituents closely mimic the side chains of hot-spot residues located on the α-helix of CaV2.2α1 Site-directed mutagenesis confirmed the critical nature of a salt-bridge interaction between the compounds and CaVβ3 Arg-307. In cells, compounds decreased trafficking of CaV2.2 channels to the plasma membrane and modulated the functions of the channel. In a rodent neuropathic pain model, the compounds suppressed pain responses. Small-molecule α-helical mimetics targeting ion channel protein-protein interactions may represent a strategy for developing nonopioid analgesia and for treatment of other neurological disorders associated with calcium-channel trafficking.}, } @article {pmid30355399, year = {2018}, author = {Dazas, M and Badell, E and Carmi-Leroy, A and Criscuolo, A and Brisse, S}, title = {Taxonomic status of Corynebacterium diphtheriae biovar Belfanti and proposal of Corynebacterium belfantii sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3826-3831}, doi = {10.1099/ijsem.0.003069}, pmid = {30355399}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Corynebacterium diphtheriae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; France ; Genes, Bacterial ; Humans ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Respiratory System/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {Clinical isolates belonging to Corynebacterium diphtheriae biovar Belfanti were characterized by genomic sequencing and biochemical and chemotaxonomic analyses. Phylogenetic analyses indicated that biovar Belfanti represents a branch that is clearly demarcated from C. diphtheriae strains of biovars Mitis and Gravis. The average nucleotide identity of isolates of biovar Belfanti with C. diphtheriae type strain NCTC 11397T (biovar Gravis) was 94.85 %. The inability to reduce nitrate differentiated biovar Belfanti from other strains of C. diphtheriae. On the basis of these results, we propose the name Corynebacterium belfantii sp. nov. for the group of strains previously considered as C. diphtheriaebiovar Belfanti. The type strain of C. belfantii is FRC0043T (=CIP 111412T=DSM 105776T). Strains of C. belfantii were isolated mostly from human respiratory samples.}, } @article {pmid30355396, year = {2018}, author = {Bae, SS and Kim, MR and Jung, Y and Yang, SH and Kwon, KK and Baek, K}, title = {Flavobacterium sediminis sp. nov., a starch-degrading bacterium isolated from tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3886-3891}, doi = {10.1099/ijsem.0.003081}, pmid = {30355396}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A yellow-pigmented bacterium with the ability to degrade starch, designated MEBiC07310T, was isolated from tidal flat sediment collected in Taean County, Republic of Korea. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that strain MEBiC07310T was affiliated with the genus Flavobacterium in the phylum Bacteroidetes and showed that the strain was most closely related to Flavobacterium haoranii LQY-7T (96.8 % similarity), followed by Flavobacterium indicum GPTSA 100-9T (95.2 %) and Flavobacterium urocaniciphilum YIT 12746T (94.6 %). Genome-based analysis of the average nucleotide identity (ANI) and in silico DNA-DNA hybridization (DDH) of strain MEBiC07310T compared with F. haoranii LQY-7T and F. indicum GPTSA 100-9T yielded ANI values of 77.0 and 73.3 % and DDH values of 18.0±2.7 and 16.1±3.6 %, respectively. The DNA G+C content of strain MEBiC07310T was 35.2 mol%. Cells of the strain were aerobic, Gram-stain-negative and rod-shaped, and negative for flexirubin-type pigments. Growth was observed at 17-43 °C (optimum 32 °C), at pH 5.0-8.0 (optimum pH 7.0) and with 0-3 % (w/v) NaCl (optimum 1 %). The major fatty acids (>10 %) of strain MEBiC07310T were iso-C15 : 0, iso-C17 : 0 3-OH, summed feature 1 (iso-C15 : 1 H and/or C13 : 0 3-OH) and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The major respiratory quinone was menaquinone MK-6. Based on its phenotypic and genotypic characteristics, strain MEBiC07310T should be classified as representing a novel species of the genus Flavobacterium, for which the name Flavobacterium sediminis sp. nov. is proposed. The type strain is MEBiC07310T (=KCTC 62132T=JCM 32291T).}, } @article {pmid30355348, year = {2018}, author = {Tackmann, J and Arora, N and Schmidt, TSB and Rodrigues, JFM and von Mering, C}, title = {Ecologically informed microbial biomarkers and accurate classification of mixed and unmixed samples in an extensive cross-study of human body sites.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {192}, pmid = {30355348}, issn = {2049-2618}, abstract = {BACKGROUND: The identification of body site-specific microbial biomarkers and their use for classification tasks have promising applications in medicine, microbial ecology, and forensics. Previous studies have characterized site-specific microbiota and shown that sample origin can be accurately predicted by microbial content. However, these studies were usually restricted to single datasets with consistent experimental methods and conditions, as well as comparatively small sample numbers. The effects of study-specific biases and statistical power on classification performance and biomarker identification thus remain poorly understood. Furthermore, reliable detection in mixtures of different body sites or with noise from environmental contamination has rarely been investigated thus far. Finally, the impact of ecological associations between microbes on biomarker discovery was usually not considered in previous work.

RESULTS: Here we present the analysis of one of the largest cross-study sequencing datasets of microbial communities from human body sites (15,082 samples from 57 publicly available studies). We show that training a Random Forest Classifier on this aggregated dataset increases prediction performance for body sites by 35% compared to a single-study classifier. Using simulated datasets, we further demonstrate that the source of different microbial contributions in mixtures of different body sites or with soil can be detected starting at 1% of the total microbial community. We apply a biomarker selection method that excludes indirect environmental associations driven by microbe-microbe associations, yielding a parsimonious set of highly predictive taxa including novel biomarkers and excluding many previously reported taxa. We find a considerable fraction of unclassified biomarkers ("microbial dark matter") and observe that negatively associated taxa have a surprisingly high impact on classification performance. We further detect a significant enrichment of rod-shaped, motile, and sporulating taxa for feces biomarkers, consistent with a highly competitive environment.

CONCLUSIONS: Our machine learning model shows strong body site classification performance, both in single-source samples and mixtures, making it promising for tasks requiring high accuracy, such as forensic applications. We report a core set of ecologically informed biomarkers, inferred across a wide range of experimental protocols and conditions, providing the most concise, general, and least biased overview of body site-associated microbes to date.}, } @article {pmid30355342, year = {2018}, author = {Güven Gökmen, T and Kalayci, Y and Yaman, A and Köksal, F}, title = {Molecular characterization of methicillin-resistant Staphylococcus aureus strains by spa typing and pulsed field gel electrophoresis methods.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {155}, pmid = {30355342}, issn = {1471-2180}, abstract = {BACKGROUND: Rapid detection of sources and transmission routes by molecular methods provides key data for risk management of methicillin-resistant Staphylococcus aureus-induced infections acquired in both the community and hospitals. This study aimed to determine the clonal relationship of methicillin-resistant S. aureus strains isolated from our hospital by pulsed-field gel electrophoresis (PFGE) and Staphylococcal protein A (spa) typing methods and to identify the predominant clones in Cukurova Region, Turkey.

RESULTS: All isolates analyzed by PFGE were distributed among 11 clusters. Clusters A (n = 19) and B (n = 27) were 84.1% similar and accounted for 61% of all samples. All isolates were distributed among 18 spa types, with the most common type being t030 with 31 isolates (41.3%), followed by t223 with nine isolates (12%) and t127 with seven isolates (9.3%).

CONCLUSIONS: We found that t030 was the most common spa type in the area where the study was conducted, as also previously shown in studies undertaken in Turkey. However, the rate of t030 in our study was below the rates reported in the literature. We also detected some rare or sporadic spa types like t127, which has not been previously defined in our country. We consider that the spa typing and PFGE methods are useful for research on clonal relations in monitoring the changing prevalent clones in specific regions.}, } @article {pmid30355340, year = {2018}, author = {Mailhe, M and Ricaboni, D and Vitton, V and Gonzalez, JM and Bachar, D and Dubourg, G and Cadoret, F and Robert, C and Delerce, J and Levasseur, A and Fournier, PE and Angelakis, E and Lagier, JC and Raoult, D}, title = {Repertoire of the gut microbiota from stomach to colon using culturomics and next-generation sequencing.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {157}, pmid = {30355340}, issn = {1471-2180}, support = {Méditerranée Infection 10-IAHU-03//French Government through the Agence Nationale pour la Recherche/ ; }, abstract = {BACKGROUND: Most studies on the human microbiota have analyzed stool samples, although a large proportion of the absorption of nutrients takes place in upper gut tract. We collected samples from different locations along the entire gastrointestinal tract from six patients who had simultaneously undergone upper endoscopy and colonoscopy, to perform a comprehensive analysis using culturomics with matrix assisted laser desorption ionisation - time of flight (MALDI-TOF) identification and by metagenomics targeting the 16S ribosomal ribonucleic acid (rRNA) gene.

RESULTS: Using culturomics, we isolated 368 different bacterial species, including 37 new species. Fewer species were isolated in the upper gut: 110 in the stomach and 106 in the duodenum, while 235 were isolated from the left colon (p < 0.02). We isolated fewer aero-intolerant species in the upper gut: 37 from the stomach and 150 from the left colon (p < 0.004). Using metagenomics, 1,021 species were identified. The upper gut microbiota was revealed to be less rich than the lower gut microbiota, with 37,622 reads from the stomach, 28,390 from the duodenum, and 79,047 from the left colon (p < 0.009). There were fewer reads for aero-intolerant species in the upper gut (8,656 in the stomach, 5,188 in the duodenum and 72,262 in the left colon, p < 0.02). Patients taking proton pump inhibitors (PPI) were then revealed to have a higher stomach pH and a greater diversity of species in the upper digestive tract than patients not receiving treatment (p < 0.001).

CONCLUSION: Significant modifications in bacterial composition and diversity exist throughout the gastrointestinal tract. We suggest that the upper gut may be key to understanding the relationship between the gut microbiota and health.}, } @article {pmid30355338, year = {2018}, author = {Lin, SJ and Lu, TP and Yu, QY and Hsiao, CK}, title = {Probabilistic prioritization of candidate pathway association with pathway score.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {391}, pmid = {30355338}, issn = {1471-2105}, support = {MOST 106-2314-B-002 -097 -MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Bayes Theorem ; Breast Neoplasms/genetics ; Computer Simulation ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Genetic Association Studies ; Genetic Markers ; Humans ; *Probability ; *Signal Transduction ; }, abstract = {BACKGROUND: Current methods for gene-set or pathway analysis are usually designed to test the enrichment of a single gene-set. Once the analysis is carried out for each of the sets under study, a list of significant sets can be obtained. However, if one wishes to further prioritize the importance or strength of association of these sets, no such quantitative measure is available. Using the magnitude of p-value to rank the pathways may not be appropriate because p-value is not a measure for strength of significance. In addition, when testing each pathway, these analyses are often implicitly affected by the number of differentially expressed genes included in the set and/or affected by the dependence among genes.

RESULTS: Here we propose a two-stage procedure to prioritize the pathways/gene-sets. In the first stage we develop a pathway-level measure with three properties. First, it contains all genes (differentially expressed or not) in the same set, and summarizes the collective effect of all genes per sample. Second, this pathway score accounts for the correlation between genes by synchronizing their correlation directions. Third, the score includes a rank transformation to enhance the variation among samples as well as to avoid the influence of extreme heterogeneity among genes. In the second stage, all scores are included simultaneously in a Bayesian logistic regression model which can evaluate the strength of association for each set and rank the sets based on posterior probabilities. Simulations from Gaussian distributions and human microarray data, and a breast cancer study with RNA-Seq are considered for demonstration and comparison with other existing methods.

CONCLUSIONS: The proposed summary pathway score provides for each sample an overall evaluation of gene expression in a gene-set. It demonstrates the advantages of including all genes in the set and the synchronization of correlation direction. The simultaneous utilization of all pathway-level scores in a Bayesian model not only offers a probabilistic evaluation and ranking of the pathway association but also presents good accuracy in identifying the top-ranking pathways. The resulting recommendation list of ranked pathways can be a reference for potential target therapy or for future allocation of research resources.}, } @article {pmid30355324, year = {2018}, author = {Naorem, SS and Han, J and Zhang, SY and Zhang, J and Graham, LB and Song, A and Smith, CV and Rashid, F and Guo, H}, title = {Efficient transposon mutagenesis mediated by an IPTG-controlled conditional suicide plasmid.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {158}, pmid = {30355324}, issn = {1471-2180}, abstract = {BACKGROUND: Transposon mutagenesis is highly valuable for bacterial genetic and genomic studies. The transposons are usually delivered into host cells through conjugation or electroporation of a suicide plasmid. However, many bacterial species cannot be efficiently conjugated or transformed for transposon saturation mutagenesis. For this reason, temperature-sensitive (ts) plasmids have also been developed for transposon mutagenesis, but prolonged incubation at high temperatures to induce ts plasmid loss can be harmful to the hosts and lead to enrichment of mutants with adaptive genetic changes. In addition, the ts phenotype of a plasmid is often strain- or species-specific, as it may become non-ts or suicidal in different bacterial species.

RESULTS: We have engineered several conditional suicide plasmids that have a broad host range and whose loss is IPTG-controlled. One construct, which has the highest stability in the absence of IPTG induction, was then used as a curable vector to deliver hyperactive miniTn5 transposons for insertional mutagenesis. Our analyses show that these new tools can be used for efficient and regulatable transposon mutagenesis in Escherichia coli, Acinetobacter baylyi and Pseudomonas aeruginosa. In P. aeruginosa PAO1, we have used this method to generate a Tn5 insertion library with an estimated diversity of ~ 108, which is ~ 2 logs larger than the best transposon insertional library of PAO1 and related Pseudomonas strains previously reported.

CONCLUSION: We have developed a number of IPTG-controlled conditional suicide plasmids. By exploiting one of them for transposon delivery, a highly efficient and broadly useful mutagenesis system has been developed. As the assay condition is mild, we believe that our methodology will have broad applications in microbiology research.}, } @article {pmid30355315, year = {2018}, author = {Nishimura, M and Kawakami, S and Otsuka, H}, title = {Molecular cloning and characterization of vanillin dehydrogenase from Streptomyces sp. NL15-2K.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {154}, pmid = {30355315}, issn = {1471-2180}, abstract = {BACKGROUND: Streptomyces sp. NL15-2K, previously isolated from the forest soil, features an extensive catabolic network for lignin-derived aromatic compounds, including pathways transforming ferulic acid to vanillin, vanillic acid, and protocatechuic acid. To successfully use Streptomyces sp. NL15-2K as a biocatalyst for vanillin production, it is necessary to characterize the vanillin dehydrogenase (VDH) that degrades the produced vanillin to vanillic acid, as well as the gene encoding this enzyme. Here, we cloned the VDH-encoding gene (vdh) from strain NL15-2K and comprehensively characterized its gene product.

RESULTS: The vdh open reading frame contains 1488 bp and encodes a 496-amino-acid protein with a calculated molecular mass of 51,705 Da. Whereas the apparent native molecular mass of recombinant VDH was estimated to be 214 kDa by gel filtration analysis, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a subunit molecular mass of ca. 56 kDa, indicating that VDH is a homotetramer. The recombinant enzyme showed optimal activity at 45 °C and pH 9.5. The VDH substrate specificity followed this order: vanillin (100%) > protocatechualdehyde (91%) > benzaldehyde (79%) > p-hydroxybenzaldehyde (56%) > isovanillin (49%) ≈ salicylaldehyde (48%) > anisaldehyde (15%) ≈ veratraldehyde (12%). Although peptide mass fingerprinting and BLAST searches indicated that this enzyme is a salicylaldehyde dehydrogenase (SALDH), the determined kinetic parameters clearly demonstrated that the enzyme is a vanillin dehydrogenase. Lastly, phylogenetic analysis revealed that VDH from Streptomyces sp. NL15-2K forms an independent branch in the phylogenetic tree and, hence, is evolutionarily distinct from other VDHs and SALDHs whose activities have been confirmed experimentally.

CONCLUSIONS: Our findings not only enhance the understanding of the enzymatic properties of VDH and the characteristics of its amino acid sequence, but also contribute to the development of Streptomyces sp. NL15-2K into a biocatalyst for the biotransformation of ferulic acid to vanillin.}, } @article {pmid30355311, year = {2018}, author = {Guo, X and Tang, Y and Zhu, W}, title = {Distinct esophageal adenocarcinoma molecular subtype has subtype-specific gene expression and mutation patterns.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {769}, pmid = {30355311}, issn = {1471-2164}, support = {81602362//National Natural Science Foundation of China/ ; 162102310391//program for Science and Technology Development in Henan Province/ ; 2016GGJS-214//program for Young Key Teacher of Henan Province/ ; 18HASTIT048//program for Innovative Talents of Science and Technology in Henan Province/ ; 2015YBZR048//supporting grants of Henan University/ ; yqpy20170039//supporting grants of Henan University/ ; B2015151//supporting grants of Henan University/ ; H2016012//Yellow River Scholar Program/ ; }, abstract = {BACKGROUND: Esophageal carcinoma (EC), consists of two histological types, esophageal squamous carcinoma (ESCC) and esophageal adenocarcinoma (EAC). EAC accounted for 10% of EC for centuries; however, the prevalence of EAC has alarmingly risen 6 times and increased to about 50% of EC in recent 30 years in the western countries, while treatment options for EAC patients are still limited. Stratification of molecular subtypes by gene expression profiling methods had offered opportunities for targeted therapies. However, the molecular subtype in EAC has not been defined. Hence, Identification of EAC molecular subtypes is needed and will provide important insights for future new therapies.

RESULTS: We performed meta-analysis of gene expression profiling data on three independent EAC cohorts and showed that there are two common molecular subtypes in EAC. Each of the two EAC molecular subtypes has subtype specific expression patterns and mutation signatures. Genes which were over-expressed in subtype I EACs rather than subtype II EAC cases, were enriched in biological processes including epithelial cell differentiation, keratinocyte differentiation, and KEGG pathways including basal cell carcinoma. TP53 and CDKN2A are significantly mutated in both EAC subtypes. 24 genes including SMAD4 were found to be only significantly mutated in subtype I EAC cases, while 30 genes including ARID1A are only significantly mutated in subtype II EACs.

CONCLUSION: Two EAC molecular subtypes were defined and validated. This finding may offer new opportunities for targeted therapies.}, } @article {pmid30355308, year = {2018}, author = {Ma, D and Huang, X and Hou, J and Ma, Y and Han, Q and Hou, G and Wang, C and Guo, T}, title = {Quantitative analysis of the grain amyloplast proteome reveals differences in metabolism between two wheat cultivars at two stages of grain development.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {768}, pmid = {30355308}, issn = {1471-2164}, support = {2016YFD0300400//the National Key Research and Development Program of China/ ; 162300410137//the Natural Science Foundation of Henan Province/ ; }, abstract = {BACKGROUND: Wheat (Triticum aestivum L.) is one of the world's most important grain crops. The amyloplast, a specialized organelle, is the major site for starch synthesis and storage in wheat grain. Understanding the metabolism in amyloplast during grain development in wheat cultivars with different quality traits will provide useful information for potential yield and quality improvement.

RESULTS: Two wheat cultivars, ZM366 and YM49-198 that differ in kernel hardness and starch characteristics, were used to examine the metabolic changes in amyloplasts at 10 and 15 days after anthesis (DAA) using label-free-based proteome analysis. We identified 523 differentially expressed proteins (DEPs) between 10 DAA and 15 DAA, and 229 DEPs between ZM366 and YM49-198. These DEPs mainly participate in eight biochemical processes: carbohydrate metabolism, nitrogen metabolism, stress/defense, transport, energetics-related, signal transduction, protein synthesis/assembly/degradation, and nucleic acid-related processes. Among these proteins, the DEPs showing higher expression levels at 10 DAA are mainly involved in carbohydrate metabolism, stress/defense, and nucleic acid related processes, whereas DEPs with higher expression levels at 15 DAA are mainly carbohydrate metabolism, energetics-related, and transport-related proteins. Among the DEPs between the two cultivars, ZM366 had more up-regulated proteins than YM49-198, and these are mainly involved in carbohydrate metabolism, nucleic acid-related processes, and transport.

CONCLUSIONS: The results of our study indicate that wheat grain amyloplast has the broad metabolic capability. The DEPs involved in carbohydrate metabolism, nucleic acids, stress/defense, and transport processes, with grain development and cultivar differences, are possibly responsible for different grain characteristics, especially with respect to yield and quality-related traits.}, } @article {pmid30355304, year = {2018}, author = {Zhang, Z and Wang, J and Gong, Y and Li, Y}, title = {Contributions of substitutions and indels to the structural variations in ancient protein superfamilies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {771}, pmid = {30355304}, issn = {1471-2164}, support = {31670076//National Natural Science Foundation of China/ ; 31471183//National Natural Science Foundation of China/ ; ZR2016QZ002//Key Program of Shandong Natural Science Foundation/ ; }, abstract = {BACKGROUND: Quantitative evaluation of protein structural evolution is important for our understanding of protein biological functions and their evolutionary adaptation, and is useful in guiding protein engineering. However, compared to the models for sequence evolution, the quantitative models for protein structural evolution received less attention. Ancient protein superfamilies are often considered versatile, allowing genetic and functional diversifications during long-term evolution. In this study, we investigated the quantitative impacts of sequence variations on the structural evolution of homologues in 68 ancient protein superfamilies that exist widely in sequenced eukaryotic, bacterial and archaeal genomes.

RESULTS: We found that the accumulated structural variations within ancient superfamilies could be explained largely by a bilinear model that simultaneously considers amino acid substitution and insertion/deletion (indel). Both substitutions and indels are essential for explaining the structural variations within ancient superfamilies. For those ancient superfamilies with high bilinear multiple correlation coefficients, the influence of each unit of substitution or indel on structural variations is almost constant within each superfamily, but varies greatly among different superfamilies. The influence of each unit indel on structural variations is always larger than that of each unit substitution within each superfamily, but the accumulated contributions of indels to structural variations are lower than those of substitutions in most superfamilies. The total contributions of sequence indels and substitutions (46% and 54%, respectively) to the structural variations that result from sequence variations are slightly different in ancient superfamilies.

CONCLUSIONS: Structural variations within ancient protein superfamilies accumulated under the significantly bilinear influence of amino acid substitutions and indels in sequences. Both substitutions and indels are essential for explaining the structural variations within ancient superfamilies. For those structural variations resulting from sequence variations, the total contribution of indels is slightly lower than that of amino acid substitutions. The regular clock exists not only in protein sequences, but also probably in protein structures.}, } @article {pmid30355302, year = {2018}, author = {Bradwell, KR and Koparde, VN and Matveyev, AV and Serrano, MG and Alves, JMP and Parikh, H and Huang, B and Lee, V and Espinosa-Alvarez, O and Ortiz, PA and Costa-Martins, AG and Teixeira, MMG and Buck, GA}, title = {Genomic comparison of Trypanosoma conorhini and Trypanosoma rangeli to Trypanosoma cruzi strains of high and low virulence.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {770}, pmid = {30355302}, issn = {1471-2164}, support = {DEB-#080056//National Science Foundation/ ; #2013/14622-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, abstract = {BACKGROUND: Trypanosoma conorhini and Trypanosoma rangeli, like Trypanosoma cruzi, are kinetoplastid protist parasites of mammals displaying divergent hosts, geographic ranges and lifestyles. Largely nonpathogenic T. rangeli and T. conorhini represent clades that are phylogenetically closely related to the T. cruzi and T. cruzi-like taxa and provide insights into the evolution of pathogenicity in those parasites. T. rangeli, like T. cruzi is endemic in many Latin American countries, whereas T. conorhini is tropicopolitan. T. rangeli and T. conorhini are exclusively extracellular, while T. cruzi has an intracellular stage in the mammalian host.

RESULTS: Here we provide the first comprehensive sequence analysis of T. rangeli AM80 and T. conorhini 025E, and provide a comparison of their genomes to those of T. cruzi G and T. cruzi CL, respectively members of T. cruzi lineages TcI and TcVI. We report de novo assembled genome sequences of the low-virulent T. cruzi G, T. rangeli AM80, and T. conorhini 025E ranging from ~ 21-25 Mbp, with ~ 10,000 to 13,000 genes, and for the highly virulent and hybrid T. cruzi CL we present a ~ 65 Mbp in-house assembled haplotyped genome with ~ 12,500 genes per haplotype. Single copy orthologs of the two T. cruzi strains exhibited ~ 97% amino acid identity, and ~ 78% identity to proteins of T. rangeli or T. conorhini. Proteins of the latter two organisms exhibited ~ 84% identity. T. cruzi CL exhibited the highest heterozygosity. T. rangeli and T. conorhini displayed greater metabolic capabilities for utilization of complex carbohydrates, and contained fewer retrotransposons and multigene family copies, i.e. trans-sialidases, mucins, DGF-1, and MASP, compared to T. cruzi.

CONCLUSIONS: Our analyses of the T. rangeli and T. conorhini genomes closely reflected their phylogenetic proximity to the T. cruzi clade, and were largely consistent with their divergent life cycles. Our results provide a greater context for understanding the life cycles, host range expansion, immunity evasion, and pathogenesis of these trypanosomatids.}, } @article {pmid30355296, year = {2018}, author = {Nishihata, S and Kondo, T and Tanaka, K and Ishikawa, S and Takenaka, S and Kang, CM and Yoshida, KI}, title = {Bradyrhizobium diazoefficiens USDA110 PhaR functions for pleiotropic regulation of cellular processes besides PHB accumulation.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {156}, pmid = {30355296}, issn = {1471-2180}, abstract = {BACKGROUND: Bradyrhizobium diazoefficiens USDA110 nodulates soybeans for nitrogen fixation. It accumulates poly-3-hydroxybutyrate (PHB), which is of physiological importance as a carbon/energy source for survival during starvation, infection, and nitrogen fixation conditions. PHB accumulation is orchestrated by not only the enzymes for PHB synthesis but also PHB-binding phasin proteins (PhaPs) stabilizing the PHB granules. The transcription factor PhaR controls the phaP genes.

RESULTS: Inactivation of phaR led to decreases in PHB accumulation, less cell yield, increases in exopolysaccharide (EPS) production, some improvement in heat stress tolerance, and slightly better growth under microaerobic conditions. Changes in the transcriptome upon phaR inactivation were analyzed. PhaR appeared to be involved in the repression of various target genes, including some PHB-degrading enzymes and others involved in EPS production. Furthermore, in vitro gel shift analysis demonstrated that PhaR bound to the promoter regions of representative targets. For the phaP1 and phaP4 promoter regions, PhaR-binding sites were determined by DNase I footprinting, allowing us to deduce a consensus sequence for PhaR-binding as TGCRNYGCASMA (R: A or G, Y: C or T, S: C or G, M: A or C). We searched for additional genes associated with a PhaR-binding sequence and found that some genes involved in central carbon metabolism, such as pdhA for pyruvate dehydrogenase and pckA for phosphoenolpyruvate carboxykinase, may be regulated positively and directly by PhaR.

CONCLUSIONS: These results suggest that PhaR could regulate various genes not only negatively but also positively to coordinate metabolism holistically in response to PHB accumulation.}, } @article {pmid30355288, year = {2018}, author = {Gysi, DM and Voigt, A and Fragoso, TM and Almaas, E and Nowick, K}, title = {wTO: an R package for computing weighted topological overlap and a consensus network with integrated visualization tool.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {392}, pmid = {30355288}, issn = {1471-2105}, support = {GDE 204111/2014-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Algorithms ; Computational Biology/*methods ; *Consensus ; Escherichia coli/metabolism ; Gene Ontology ; *Gene Regulatory Networks ; Humans ; *Metabolic Networks and Pathways ; Metagenomics ; Oceans and Seas ; ROC Curve ; *Software ; Time Factors ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: Network analyses, such as of gene co-expression networks, metabolic networks and ecological networks have become a central approach for the systems-level study of biological data. Several software packages exist for generating and analyzing such networks, either from correlation scores or the absolute value of a transformed score called weighted topological overlap (wTO). However, since gene regulatory processes can up- or down-regulate genes, it is of great interest to explicitly consider both positive and negative correlations when constructing a gene co-expression network.

RESULTS: Here, we present an R package for calculating the weighted topological overlap (wTO), that, in contrast to existing packages, explicitly addresses the sign of the wTO values, and is thus especially valuable for the analysis of gene regulatory networks. The package includes the calculation of p-values (raw and adjusted) for each pairwise gene score. Our package also allows the calculation of networks from time series (without replicates). Since networks from independent datasets (biological repeats or related studies) are not the same due to technical and biological noise in the data, we additionally, incorporated a novel method for calculating a consensus network (CN) from two or more networks into our R package. To graphically inspect the resulting networks, the R package contains a visualization tool, which allows for the direct network manipulation and access of node and link information. When testing the package on a standard laptop computer, we can conduct all calculations for systems of more than 20,000 genes in under two hours. We compare our new wTO package to state of art packages and demonstrate the application of the wTO and CN functions using 3 independently derived datasets from healthy human pre-frontal cortex samples. To showcase an example for the time series application we utilized a metagenomics data set.

CONCLUSION: In this work, we developed a software package that allows the computation of wTO networks, CNs and a visualization tool in the R statistical environment. It is publicly available on CRAN repositories under the GPL -2 Open Source License (https://cran.r-project.org/web/packages/wTO/).}, } @article {pmid30355281, year = {2018}, author = {Sadre-Marandi, F and Dahdoul, T and Reed, MC and Nijhout, HF}, title = {Sex differences in hepatic one-carbon metabolism.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {89}, pmid = {30355281}, issn = {1752-0509}, support = {R21 MH109959/MH/NIMH NIH HHS/United States ; IOS-1557341//National Science Foundation/ ; 1R01MH106563-01A1//National Institutes of Health/ ; R01 MH106563/MH/NIMH NIH HHS/United States ; IOS-1562701//National Science Foundation/ ; EF-1038593//National Science Foundation/ ; 1R21MH109959-01A1//National Institutes of Health/ ; }, abstract = {BACKGROUND: There are large differences between men and women of child-bearing age in the expression level of 5 key enzymes in one-carbon metabolism almost certainly caused by the sex hormones. These male-female differences in one-carbon metabolism are greatly accentuated during pregnancy. Thus, understanding the origin and consequences of sex differences in one-carbon metabolism is important for precision medicine.

RESULTS: We have created a mathematical model of hepatic one-carbon metabolism based on the underlying physiology and biochemistry. We use the model to investigate the consequences of sex differences in gene expression. We give a mechanistic understanding of observed concentration differences in one-carbon metabolism and explain why women have lower S-andenosylmethionine, lower homocysteine, and higher choline and betaine. We give a new explanation of the well known phenomenon that folate supplementation lowers homocysteine and we show how to use the model to investigate the effects of vitamin deficiencies, gene polymorphisms, and nutrient input changes.

CONCLUSIONS: Our model of hepatic one-carbon metabolism is a useful platform for investigating the mechanistic reasons that underlie known associations between metabolites. In particular, we explain how gene expression differences lead to metabolic differences between males and females.}, } @article {pmid30353655, year = {2018}, author = {Li, XY and Kokko, H}, title = {Sex-biased dispersal: a review of the theory.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12475}, pmid = {30353655}, issn = {1469-185X}, support = {//Swiss National Science Foundation/ ; }, abstract = {Dispersal is ubiquitous throughout the tree of life: factors selecting for dispersal include kin competition, inbreeding avoidance and spatiotemporal variation in resources or habitat suitability. These factors differ in whether they promote male and female dispersal equally strongly, and often selection on dispersal of one sex depends on how much the other disperses. For example, for inbreeding avoidance it can be sufficient that one sex disperses away from the natal site. Attempts to understand sex-specific dispersal evolution have created a rich body of theoretical literature, which we review here. We highlight an interesting gap between empirical and theoretical literature. The former associates different patterns of sex-biased dispersal with mating systems, such as female-biased dispersal in monogamous birds and male-biased dispersal in polygynous mammals. The predominant explanation is traceable back to Greenwood's () ideas of how successful philopatric or dispersing individuals are at gaining mates or the resources required to attract them. Theory, however, has developed surprisingly independently of these ideas: models typically track how immigration and emigration change relatedness patterns and alter competition for limiting resources. The limiting resources are often considered sexually distinct, with breeding sites and fertilizable females limiting reproductive success for females and males, respectively. We show that the link between mating system and sex-biased dispersal is far from resolved: there are studies showing that mating systems matter, but the oft-stated association between polygyny and male-biased dispersal is not a straightforward theoretical expectation. Here, an important understudied factor is the extent to which movement is interpretable as an extension of mate-searching (e.g. are matings possible en route or do they only happen after settling in new habitat - or can females perhaps move with stored sperm). We also point out other new directions for bridging the gap between empirical and theoretical studies: there is a need to build Greenwood's influential yet verbal explanation into formal models, which also includes the possibility that an individual benefits from mobility as it leads to fitness gains in more than one final breeding location (a possibility not present in models with a very rigid deme structure). The order of life-cycle events is likewise important, as this impacts whether a departing individual leaves behind important resources for its female or male kin, or perhaps both, in the case of partially overlapping resource use.}, } @article {pmid30353215, year = {2019}, author = {Pannu, MK and Hudman, DA and Sargentini, NJ and Singh, VK}, title = {Role of SigB and Staphyloxanthin in Radiation Survival of Staphylococcus aureus.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {70-77}, doi = {10.1007/s00284-018-1586-x}, pmid = {30353215}, issn = {1432-0991}, support = {850-608//KCOM Biomedical Sciences Program/ ; }, abstract = {Staphylococcus aureus is a potent human pathogen. The virulence of this bacterium depends on a multitude of factors that it produces. One such virulence factor is the golden pigment, staphyloxanthin, which has been shown to protect the bacterium from oxidative stress. Expression of the staphyloxanthin biosynthetic pathway is dependent on SigB, a global stress response regulator in S. aureus. This study investigated the role of staphyloxanthin and SigB in protection of S. aureus from radiation damage. Using stationary-phase bacterial cells, it was determined that the staphyloxanthin-deficient (crt mutant) strain was significantly sensitive to UV radiation (~ threefold), but not sensitive to X-radiation. However, a SigB-deficient S. aureus that also lacks staphyloxanthin, was significantly sensitive to both UV- and X-radiation. To confirm that protection from X-radiation was due to hydroxyl radicals, effect of 3 M glycerol, a known hydroxyl scavenger, was also investigated. Glycerol increased the survival of the S. aureus sigB mutant to the wild-type level suggesting that the X-radiation sensitivity of these mutants was due to deficiency in scavenging hydroxyl radicals. In summary, SigB is critical for protection of S. aureus cells from radiation damage.}, } @article {pmid30353162, year = {2018}, author = {Irwin, A}, title = {No PhDs needed: how citizen science is transforming research.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {480-482}, doi = {10.1038/d41586-018-07106-5}, pmid = {30353162}, issn = {1476-4687}, } @article {pmid30353161, year = {2018}, author = {Ravilious, K}, title = {Italian earthquake data hint at possibility of forecasting one type of quake.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {470-471}, doi = {10.1038/d41586-018-07017-5}, pmid = {30353161}, issn = {1476-4687}, } @article {pmid30353160, year = {2018}, author = {}, title = {Back the idea of human capital with solid research.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {459-460}, doi = {10.1038/d41586-018-07151-0}, pmid = {30353160}, issn = {1476-4687}, } @article {pmid30353159, year = {2018}, author = {Parthasarathy, S}, title = {Use the patent system to regulate gene editing.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {486-488}, doi = {10.1038/d41586-018-07108-3}, pmid = {30353159}, issn = {1476-4687}, } @article {pmid30353158, year = {2018}, author = {Cisse, M}, title = {Look to Africa to advance artificial intelligence.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {461}, doi = {10.1038/d41586-018-07104-7}, pmid = {30353158}, issn = {1476-4687}, } @article {pmid30353157, year = {2018}, author = {Schiermeier, Q}, title = {British universities set up European outposts as Brexit looms.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {467-468}, doi = {10.1038/d41586-018-07121-6}, pmid = {30353157}, issn = {1476-4687}, } @article {pmid30353156, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {500}, doi = {10.1038/d41586-018-07100-x}, pmid = {30353156}, issn = {1476-4687}, } @article {pmid30353155, year = {2018}, author = {Reardon, S}, title = {Virus detectives test whole-body scans in search of HIV's hiding places.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {472-473}, doi = {10.1038/d41586-018-07115-4}, pmid = {30353155}, issn = {1476-4687}, } @article {pmid30353154, year = {2018}, author = {Witze, A}, title = {Double the fun: Mars scientists push NASA to send rock-harvesting rover to two sites.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {468-469}, doi = {10.1038/d41586-018-07064-y}, pmid = {30353154}, issn = {1476-4687}, } @article {pmid30353153, year = {2018}, author = {Cyranoski, D}, title = {China awaits controversial blacklist of 'poor quality' journals.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {471-472}, doi = {10.1038/d41586-018-07025-5}, pmid = {30353153}, issn = {1476-4687}, } @article {pmid30352870, year = {2018}, author = {Porsdam Mann, S and Donders, Y and Mitchell, C and Bradley, VJ and Chou, MF and Mann, M and Church, G and Porsdam, H}, title = {Opinion: Advocating for science progress as a human right.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10820-10823}, pmid = {30352870}, issn = {1091-6490}, mesh = {History, 20th Century ; History, 21st Century ; Human Rights/*history/*trends ; Humans ; Science/*history/*trends ; }, } @article {pmid30352858, year = {2018}, author = {Rees-Jones, A and Skowronek, S}, title = {An experimental investigation of preference misrepresentation in the residency match.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11471-11476}, pmid = {30352858}, issn = {1091-6490}, abstract = {The development and deployment of matching procedures that incentivize truthful preference reporting is considered one of the major successes of market design research. In this study, we test the degree to which these procedures succeed in eliminating preference misrepresentation. We administered an online experiment to 1,714 medical students immediately after their participation in the medical residency match-a leading field application of strategy-proof market design. When placed in an analogous, incentivized matching task, we find that 23% of participants misrepresent their preferences. We explore the factors that predict preference misrepresentation, including cognitive ability, strategic positioning, overconfidence, expectations, advice, and trust. We discuss the implications of this behavior for the design of allocation mechanisms and the social welfare in markets that use them.}, } @article {pmid30352857, year = {2018}, author = {Goldhill, DH and Te Velthuis, AJW and Fletcher, RA and Langat, P and Zambon, M and Lackenby, A and Barclay, WS}, title = {The mechanism of resistance to favipiravir in influenza.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11613-11618}, pmid = {30352857}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 206579/Z/17/Z//Wellcome Trust/United Kingdom ; 200187/Z/15/Z//Wellcome Trust/United Kingdom ; }, abstract = {Favipiravir is a broad-spectrum antiviral that has shown promise in treatment of influenza virus infections. While emergence of resistance has been observed for many antiinfluenza drugs, to date, clinical trials and laboratory studies of favipiravir have not yielded resistant viruses. Here we show evolution of resistance to favipiravir in the pandemic H1N1 influenza A virus in a laboratory setting. We found that two mutations were required for robust resistance to favipiravir. We demonstrate that a K229R mutation in motif F of the PB1 subunit of the influenza virus RNA-dependent RNA polymerase (RdRP) confers resistance to favipiravir in vitro and in cell culture. This mutation has a cost to viral fitness, but fitness can be restored by a P653L mutation in the PA subunit of the polymerase. K229R also conferred favipiravir resistance to RNA polymerases of other influenza A virus strains, and its location within a highly conserved structural feature of the RdRP suggests that other RNA viruses might also acquire resistance through mutations in motif F. The mutations identified here could be used to screen influenza virus-infected patients treated with favipiravir for the emergence of resistance.}, } @article {pmid30352856, year = {2018}, author = {Sasanuma, H and Tsuda, M and Morimoto, S and Saha, LK and Rahman, MM and Kiyooka, Y and Fujiike, H and Cherniack, AD and Itou, J and Callen Moreu, E and Toi, M and Nakada, S and Tanaka, H and Tsutsui, K and Yamada, S and Nussenzweig, A and Takeda, S}, title = {BRCA1 ensures genome integrity by eliminating estrogen-induced pathological topoisomerase II-DNA complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10642-E10651}, pmid = {30352856}, issn = {1091-6490}, abstract = {Women having BRCA1 germ-line mutations develop cancer in breast and ovary, estrogen-regulated tissues, with high penetrance. Binding of estrogens to the estrogen receptor (ER) transiently induces DNA double-strand breaks (DSBs) by topoisomerase II (TOP2) and controls gene transcription. TOP2 resolves catenated DNA by transiently generating DSBs, TOP2-cleavage complexes (TOP2ccs), where TOP2 covalently binds to 5' ends of DSBs. TOP2 frequently fails to complete its catalysis, leading to formation of pathological TOP2ccs. We have previously shown that the endonucleolytic activity of MRE11 plays a key role in removing 5' TOP2 adducts in G1 phase. We show here that BRCA1 promotes MRE11-mediated removal of TOP2 adducts in G1 phase. We disrupted the BRCA1 gene in 53BP1-deficient ER-positive breast cancer and B cells. The loss of BRCA1 caused marked increases of pathological TOP2ccs in G1 phase following exposure to etoposide, which generates pathological TOP2ccs. We conclude that BRCA1 promotes the removal of TOP2 adducts from DSB ends for subsequent nonhomologous end joining. BRCA1-deficient cells showed a decrease in etoposide-induced MRE11 foci in G1 phase, suggesting that BRCA1 repairs pathological TOP2ccs by promoting the recruitment of MRE11 to TOP2cc sites. BRCA1 depletion also leads to the increase of unrepaired DSBs upon estrogen treatment both in vitro in G1-arrested breast cancer cells and in vivo in epithelial cells of mouse mammary glands. BRCA1 thus plays a critical role in removing pathological TOP2ccs induced by estrogens as well as etoposide. We propose that BRCA1 suppresses tumorigenesis by removing estrogen-induced pathological TOP2ccs throughout the cell cycle.}, } @article {pmid30352855, year = {2018}, author = {Zhao, X and Jiang, Y and Li, J and Huq, E and Chen, ZJ and Xu, D and Deng, XW}, title = {COP1 SUPPRESSOR 4 promotes seedling photomorphogenesis by repressing CCA1 and PIF4 expression in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11631-11636}, pmid = {30352855}, issn = {1091-6490}, support = {R01 GM047850/GM/NIGMS NIH HHS/United States ; R01 GM109076/GM/NIGMS NIH HHS/United States ; R01 GM114297/GM/NIGMS NIH HHS/United States ; R37 GM047850/GM/NIGMS NIH HHS/United States ; }, abstract = {CONSTITUTIVELY PHOTOMORPHOGENIC 1 (COP1) and DE-ETIOLATED 1 (DET1) are founding components of two central repressor complexes of photomorphogenesis that trigger the degradation of a larger number of photomorphogenic-promoting factors in darkness. Here, we identify COP1 SUPPRESSOR 4 (CSU4) as a genetic suppressor of the cop1-6 mutation. Mutations in CSU4 largely rescued the constitutively photomorphogenic phenotype of cop1-6 and det1-1 in darkness. Loss of CSU4 function resulted in significantly longer hypocotyl in the light. Further biochemical studies revealed that CSU4 physically interacts with CIRCADIAN CLOCK-ASSOCIATED 1 (CCA1) and negatively regulates its transcriptional repression activity toward its targets. CSU4 represses the expression of CCA1 in the early morning and of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in the early evening. Our study suggests that CSU4 acts as a negative regulator of CCA1 via physically associating with CCA1, which in turn, likely serves to repress expression of CCA1 and PIF4 to promote photomorphogenesis.}, } @article {pmid30352854, year = {2018}, author = {Cai, G and Zhu, L and Chen, X and Sun, K and Liu, C and Sen, GC and Stark, GR and Qin, J and Li, X}, title = {TRAF4 binds to the juxtamembrane region of EGFR directly and promotes kinase activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11531-11536}, pmid = {30352854}, issn = {1091-6490}, support = {P01 CA062220/CA/NCI NIH HHS/United States ; P01 HL103453/HL/NHLBI NIH HHS/United States ; R01 HL058758/HL/NHLBI NIH HHS/United States ; }, abstract = {The activation of the epidermal growth factor receptor (EGFR) is crucial for triggering diverse cellular functions, including cell proliferation, migration, and differentiation, and up-regulation of EGFR expression or activity is a key factor in triggering the development of cancer. Here we show that overexpression of a scaffold protein, tumor necrosis factor receptor (TNF-R)-associated factor 4 (TRAF4), promotes EGF-induced autophosphorylation of EGFR (activation) and downstream signaling, whereas TRAF4 deficiency attenuates EGFR activation and EGF-driven cell proliferation. Using structure-based sequence alignment and NMR spectroscopy, we identified a TRAF4 binding site in the C-terminal half of the juxtamembrane (JM) segment of EGFR, a region known to promote asymmetric dimerization and subsequent activation. Deletion of the TRAF4 binding site led to dramatic defects in EGFR activation and EGF-driven cell proliferation. Specific point mutations in the TRAF4 binding site also resulted in significant attenuation of EGFR activation. Detailed structural examination of the inactive versus active forms of EGFR suggests that TRAF4 binding probably induces a conformational rearrangement of the JM region to promote EGFR dimerization. These results identify a novel mechanism of TRAF4-mediated EGFR activation and signaling.}, } @article {pmid30352853, year = {2018}, author = {Nguyen, PT and Lai, JY and Lee, AT and Kaiser, JT and Rees, DC}, title = {Noncanonical role for the binding protein in substrate uptake by the MetNI methionine ATP Binding Cassette (ABC) transporter.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10596-E10604}, pmid = {30352853}, issn = {1091-6490}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; P41 RR001209/RR/NCRR NIH HHS/United States ; }, abstract = {The Escherichia coli methionine ABC transporter MetNI exhibits both high-affinity transport toward l-methionine and broad specificity toward methionine derivatives, including d-methionine. In this work, we characterize the transport of d-methionine derivatives by the MetNI transporter. Unexpectedly, the N229A substrate-binding deficient variant of the cognate binding protein MetQ was found to support high MetNI transport activity toward d-selenomethionine. We determined the crystal structure at 2.95 Å resolution of the ATPγS-bound MetNIQ complex in the outward-facing conformation with the N229A apo MetQ variant. This structure revealed conformational changes in MetQ providing substrate access through the binding protein to the transmembrane translocation pathway. MetQ likely mediates uptake of methionine derivatives through two mechanisms: in the methionine-bound form delivering substrate from the periplasm to the transporter (the canonical mechanism) and in the apo form by facilitating ligand binding when complexed to the transporter (the noncanonical mechanism). This dual role for substrate-binding proteins is proposed to provide a kinetic strategy for ABC transporters to transport both high- and low-affinity substrates present in a physiological concentration range.}, } @article {pmid30352852, year = {2018}, author = {Steimle, JD and Rankin, SA and Slagle, CE and Bekeny, J and Rydeen, AB and Chan, SS and Kweon, J and Yang, XH and Ikegami, K and Nadadur, RD and Rowton, M and Hoffmann, AD and Lazarevic, S and Thomas, W and Boyle Anderson, EAT and Horb, ME and Luna-Zurita, L and Ho, RK and Kyba, M and Jensen, B and Zorn, AM and Conlon, FL and Moskowitz, IP}, title = {Evolutionarily conserved Tbx5-Wnt2/2b pathway orchestrates cardiopulmonary development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10615-E10624}, pmid = {30352852}, issn = {1091-6490}, support = {R01 HL114898/HL/NHLBI NIH HHS/United States ; R01 HD084409/HD/NICHD NIH HHS/United States ; R01 HL124836/HL/NHLBI NIH HHS/United States ; R21 LM012619/LM/NLM NIH HHS/United States ; R01 DK070858/DK/NIDDK NIH HHS/United States ; R01 HL126509/HL/NHLBI NIH HHS/United States ; R21 AG054770/AG/NIA NIH HHS/United States ; P01 HD093363/HD/NICHD NIH HHS/United States ; S10 OD018495/OD/NIH HHS/United States ; T32 HL007381/HL/NHLBI NIH HHS/United States ; T32 HD055164/HD/NICHD NIH HHS/United States ; R01 HL092153/HL/NHLBI NIH HHS/United States ; T32 GM007281/GM/NIGMS NIH HHS/United States ; R01 HD072598/HD/NICHD NIH HHS/United States ; T32 GM007197/GM/NIGMS NIH HHS/United States ; U01 HL100407/HL/NHLBI NIH HHS/United States ; R01 HD089275/HD/NICHD NIH HHS/United States ; T32 GM007183/GM/NIGMS NIH HHS/United States ; P40 OD010997/OD/NIH HHS/United States ; }, abstract = {Codevelopment of the lungs and heart underlies key evolutionary innovations in the transition to terrestrial life. Cardiac specializations that support pulmonary circulation, including the atrial septum, are generated by second heart field (SHF) cardiopulmonary progenitors (CPPs). It has been presumed that transcription factors required in the SHF for cardiac septation, e.g., Tbx5, directly drive a cardiac morphogenesis gene-regulatory network. Here, we report instead that TBX5 directly drives Wnt ligands to initiate a bidirectional signaling loop between cardiopulmonary mesoderm and the foregut endoderm for endodermal pulmonary specification and, subsequently, atrial septation. We show that Tbx5 is required for pulmonary specification in mice and amphibians but not for swim bladder development in zebrafish. TBX5 is non-cell-autonomously required for pulmonary endoderm specification by directly driving Wnt2 and Wnt2b expression in cardiopulmonary mesoderm. TBX5 ChIP-sequencing identified cis-regulatory elements at Wnt2 sufficient for endogenous Wnt2 expression domains in vivo and required for Wnt2 expression in precardiac mesoderm in vitro. Tbx5 cooperated with Shh signaling to drive Wnt2b expression for lung morphogenesis. Tbx5 haploinsufficiency in mice, a model of Holt-Oram syndrome, caused a quantitative decrement of mesodermal-to-endodermal Wnt signaling and subsequent endodermal-to-mesodermal Shh signaling required for cardiac morphogenesis. Thus, Tbx5 initiates a mesoderm-endoderm-mesoderm signaling loop in lunged vertebrates that provides a molecular basis for the coevolution of pulmonary and cardiac structures required for terrestrial life.}, } @article {pmid30352851, year = {2018}, author = {Giometto, A and Nelson, DR and Murray, AW}, title = {Physical interactions reduce the power of natural selection in growing yeast colonies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11448-11453}, pmid = {30352851}, issn = {1091-6490}, abstract = {Microbial populations often assemble in dense populations in which proliferating individuals exert mechanical forces on the nearby cells. Here, we use yeast strains whose doubling times depend differently on temperature to show that physical interactions among cells affect the competition between different genotypes in growing yeast colonies. Our experiments demonstrate that these physical interactions have two related effects: they cause the prolonged survival of slower-growing strains at the actively-growing frontier of the colony and cause faster-growing strains to increase their frequency more slowly than expected in the absence of physical interactions. These effects also promote the survival of slower-growing strains and the maintenance of genetic diversity in colonies grown in time-varying environments. A continuum model inspired by overdamped hydrodynamics reproduces the experiments and predicts that the strength of natural selection depends on the width of the actively growing layer at the colony frontier. We verify these predictions experimentally. The reduced power of natural selection observed here may favor the maintenance of drug-resistant cells in microbial populations and could explain the apparent neutrality of interclone competition within tumors.}, } @article {pmid30352850, year = {2018}, author = {Voon, CP and Guan, X and Sun, Y and Sahu, A and Chan, MN and Gardeström, P and Wagner, S and Fuchs, P and Nietzel, T and Versaw, WK and Schwarzländer, M and Lim, BL}, title = {ATP compartmentation in plastids and cytosol of Arabidopsis thaliana revealed by fluorescent protein sensing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10778-E10787}, pmid = {30352850}, issn = {1091-6490}, abstract = {Matching ATP:NADPH provision and consumption in the chloroplast is a prerequisite for efficient photosynthesis. In terms of ATP:NADPH ratio, the amount of ATP generated from the linear electron flow does not meet the demand of the Calvin-Benson-Bassham (CBB) cycle. Several different mechanisms to increase ATP availability have evolved, including cyclic electron flow in higher plants and the direct import of mitochondrial-derived ATP in diatoms. By imaging a fluorescent ATP sensor protein expressed in living Arabidopsis thaliana seedlings, we found that MgATP2- concentrations were lower in the stroma of mature chloroplasts than in the cytosol, and exogenous ATP was able to enter chloroplasts isolated from 4- and 5-day-old seedlings, but not chloroplasts isolated from 10- or 20-day-old photosynthetic tissues. This observation is in line with the previous finding that the expression of chloroplast nucleotide transporters (NTTs) in Arabidopsis mesophyll is limited to very young seedlings. Employing a combination of photosynthetic and respiratory inhibitors with compartment-specific imaging of ATP, we corroborate the dependency of stromal ATP production on mitochondrial dissipation of photosynthetic reductant. Our data suggest that, during illumination, the provision and consumption of ATP:NADPH in chloroplasts can be balanced by exporting excess reductants rather than importing ATP from the cytosol.}, } @article {pmid30352849, year = {2018}, author = {Ellis, GFR}, title = {Top-down causation and quantum physics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11661-11663}, pmid = {30352849}, issn = {1091-6490}, mesh = {*Quantum Theory ; }, } @article {pmid30352848, year = {2018}, author = {Díaz-Moreno, M and Armenteros, T and Gradari, S and Hortigüela, R and García-Corzo, L and Fontán-Lozano, Á and Trejo, JL and Mira, H}, title = {Noggin rescues age-related stem cell loss in the brain of senescent mice with neurodegenerative pathology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11625-11630}, pmid = {30352848}, issn = {1091-6490}, abstract = {Increasing age is the greatest known risk factor for the sporadic late-onset forms of neurodegenerative disorders such as Alzheimer's disease (AD). One of the brain regions most severely affected in AD is the hippocampus, a privileged structure that contains adult neural stem cells (NSCs) with neurogenic capacity. Hippocampal neurogenesis decreases during aging and the decrease is exacerbated in AD, but the mechanistic causes underlying this progressive decline remain largely unexplored. We here investigated the effect of age on NSCs and neurogenesis by analyzing the senescence accelerated mouse prone 8 (SAMP8) strain, a nontransgenic short-lived strain that spontaneously develops a pathological profile similar to that of AD and that has been employed as a model system to study the transition from healthy aging to neurodegeneration. We show that SAMP8 mice display an accelerated loss of the NSC pool that coincides with an aberrant rise in BMP6 protein, enhanced canonical BMP signaling, and increased astroglial differentiation. In vitro assays demonstrate that BMP6 severely impairs NSC expansion and promotes NSC differentiation into postmitotic astrocytes. Blocking the dysregulation of the BMP pathway and its progliogenic effect in vivo by intracranial delivery of the antagonist Noggin restores hippocampal NSC numbers, neurogenesis, and behavior in SAMP8 mice. Thus, manipulating the local microenvironment of the NSC pool counteracts hippocampal dysfunction in pathological aging. Our results shed light on interventions that may allow taking advantage of the brain's natural plastic capacity to enhance cognitive function in late adulthood and in chronic neurodegenerative diseases such as AD.}, } @article {pmid30352847, year = {2018}, author = {Imai, T and Matsumura, T and Mayer-Lambertz, S and Wells, CA and Ishikawa, E and Butcher, SK and Barnett, TC and Walker, MJ and Imamura, A and Ishida, H and Ikebe, T and Miyamoto, T and Ato, M and Ohga, S and Lepenies, B and van Sorge, NM and Yamasaki, S}, title = {Lipoteichoic acid anchor triggers Mincle to drive protective immunity against invasive group A Streptococcus infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10662-E10671}, pmid = {30352847}, issn = {1091-6490}, abstract = {Group A Streptococcus (GAS) is a Gram-positive bacterial pathogen that causes a range of diseases, including fatal invasive infections. However, the mechanisms by which the innate immune system recognizes GAS are not well understood. We herein report that the C-type lectin receptor macrophage inducible C-type lectin (Mincle) recognizes GAS and initiates antibacterial immunity. Gene expression analysis of myeloid cells upon GAS stimulation revealed the contribution of the caspase recruitment domain-containing protein 9 (CARD9) pathway to the antibacterial responses. Among receptors signaling through CARD9, Mincle induced the production of inflammatory cytokines, inducible nitric oxide synthase, and reactive oxygen species upon recognition of the anchor of lipoteichoic acid, monoglucosyldiacylglycerol (MGDG), produced by GAS. Upon GAS infection, Mincle-deficient mice exhibited impaired production of proinflammatory cytokines, severe bacteremia, and rapid lethality. GAS also possesses another Mincle ligand, diglucosyldiacylglycerol; however, this glycolipid interfered with MGDG-induced activation. These results indicate that Mincle plays a central role in protective immunity against acute GAS infection.}, } @article {pmid30352846, year = {2018}, author = {Geng, C and Li, J and Weiske, T and Schwarz, H}, title = {Ta2+-mediated ammonia synthesis from N2 and H2 at ambient temperature.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11680-11687}, pmid = {30352846}, issn = {1091-6490}, abstract = {In a full catalytic cycle, bare Ta2+ in the highly diluted gas phase is able to mediate the formation of ammonia in a Haber-Bosch-like process starting from N2 and H2 at ambient temperature. This finding is the result of extensive quantum chemical calculations supported by experiments using Fourier transform ion cyclotron resonance MS. The planar Ta2N2+, consisting of a four-membered ring of alternating Ta and N atoms, proved to be a key intermediate. It is formed in a highly exothermic process either by the reaction of Ta2+ with N2 from the educt side or with two molecules of NH3 from the product side. In the thermal reaction of Ta2+ with N2, the N≡N triple bond of dinitrogen is entirely broken. A detailed analysis of the frontier orbitals involved in the rate-determining step shows that this unexpected reaction is accomplished by the interplay of vacant and doubly occupied d-orbitals, which serve as both electron acceptors and electron donors during the cleavage of the triple bond of N≡N by the ditantalum center. The ability of Ta2+ to serve as a multipurpose tool is further shown by splitting the single bond of H2 in a less exothermic reaction as well. The insight into the microscopic mechanisms obtained may provide guidance for the rational design of polymetallic catalysts to bring about ammonia formation by the activation of molecular nitrogen and hydrogen at ambient conditions.}, } @article {pmid30352845, year = {2018}, author = {Kim, DK and Cho, YE and Komarow, HD and Bandara, G and Song, BJ and Olivera, A and Metcalfe, DD}, title = {Mastocytosis-derived extracellular vesicles exhibit a mast cell signature, transfer KIT to stellate cells, and promote their activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10692-E10701}, pmid = {30352845}, issn = {1091-6490}, abstract = {Extracellular vesicles (EVs) have been implicated in the development and progression of hematological malignancies. We thus examined serum samples from patients with systemic mastocytosis (SM) and found EVs with a mast cell signature including the presence of tryptase, FcεRI, MRGX2, and KIT. The concentration of these EVs correlated with parameters of disease including levels of serum tryptase, IL-6, and alkaline phosphatase and physical findings including hepatosplenomegaly. Given reports that EVs from one cell type may influence another cell's behavior, we asked whether SM-EVs might affect hepatic stellate cells (HSCs), based on the abnormal liver pathology associated with mastocytosis. We found that KIT was transferred from SM-EVs into an HSC line eliciting proliferation, cytokine production, and differentiation, processes that have been associated with liver pathology. These effects were reduced by KIT inhibition or neutralization and recapitulated by enforced expression of KIT or constitutively active D816V-KIT, a gain-of-function variant associated with SM. Furthermore, HSCs in liver from mice injected with SM-EVs had increased expression of α-SMA and human KIT, particularly around portal areas, compared with mice injected with EVs from normal individuals, suggesting that SM-EVs can also initiate HSC activation in vivo. Our data are thus consistent with the conclusion that SM-EVs have the potential to influence cells outside the hematological compartment and that therapeutic approaches for treatment of SM may be effective in part through inhibition of effects of EVs on target tissues, findings important both to understanding complex disease pathology and in developing interventional agents for the treatment of hematologic diseases.}, } @article {pmid30352628, year = {2018}, author = {Wilmoth, JL and Moran, MA and Thompson, A}, title = {Transient O2 pulses direct Fe crystallinity and Fe(III)-reducer gene expression within a soil microbiome.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {189}, pmid = {30352628}, issn = {2049-2618}, abstract = {BACKGROUND: Many environments contain redox transition zones, where transient oxygenation events can modulate anaerobic reactions that influence the cycling of iron (Fe) and carbon (C) on a global scale. In predominantly anoxic soils, this biogeochemical cycling depends on Fe mineral composition and the activity of mixed Fe(III)-reducer populations that may be altered by periodic pulses of molecular oxygen (O2).

METHODS: We repeatedly exposed anoxic (4% H2:96% N2) suspensions of soil from the Luquillo Critical Zone Observatory to 1.05 × 102, 1.05 × 103, and 1.05 × 104 mmol O2 kg-1 soil h-1 during pulsed oxygenation treatments. Metatranscriptomic analysis and 57Fe Mössbauer spectroscopy were used to investigate changes in Fe(III)-reducer gene expression and Fe(III) crystallinity, respectively.

RESULTS: Slow oxygenation resulted in soil Fe-(oxyhydr)oxides of higher crystallinity (38.1 ± 1.1% of total Fe) compared to fast oxygenation (30.6 ± 1.5%, P < 0.001). Transcripts binning to the genomes of Fe(III)-reducers Anaeromyxobacter, Geobacter, and Pelosinus indicated significant differences in extracellular electron transport (e.g., multiheme cytochrome c, multicopper oxidase, and type-IV pilin gene expression), adhesion/contact (e.g., S-layer, adhesin, and flagellin gene expression), and selective microbial competition (e.g., bacteriocin gene expression) between the slow and fast oxygenation treatments during microbial Fe(III) reduction. These data also suggest that diverse Fe(III)-reducer functions, including cytochrome-dependent extracellular electron transport, are associated with type-III fibronectin domains. Additionally, the metatranscriptomic data indicate that Methanobacterium was significantly more active in the reduction of CO2 to CH4 and in the expression of class(III) signal peptide/type-IV pilin genes following repeated fast oxygenation compared to slow oxygenation.

CONCLUSIONS: This study demonstrates that specific Fe(III)-reduction mechanisms in mixed Fe(III)-reducer populations are uniquely sensitive to the rate of O2 influx, likely mediated by shifts in soil Fe(III)-(oxyhydr)oxide crystallinity. Overall, we provide evidence that transient oxygenation events play an important role in directing anaerobic pathways within soil microbiomes, which is expected to alter Fe and C cycling in redox-dynamic environments.}, } @article {pmid30352625, year = {2018}, author = {Landi, L and De Miccolis Angelini, RM and Pollastro, S and Abate, D and Faretra, F and Romanazzi, G}, title = {Genome sequence of the brown rot fungal pathogen Monilinia fructigena.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {758}, pmid = {30352625}, issn = {1756-0500}, support = {246//Università Politecnica delle Marche/ ; 14//Regione Puglia/ ; }, abstract = {OBJECTIVES: Monilinia fructigena (phylum Ascomycota, family Sclerotiniaceae) is a plant pathogen that causes brown rot and blossom blight in pome fruit and stone fruit of the Rosaceae family, which can cause significant losses in the field and mainly postharvest. The aim of this study was to create a high-quality draft of the M. fructigena genome assembly and annotation that provides better understanding of the epidemiology of the pathogen and its interactions with the host(s) and will thus improve brown rot management.

DATA DESCRIPTION: We report here on the genome sequence of M. fructigena strain Mfrg269 that was collected from plum in southern Italy. This is assembled into 131 scaffolds, with a total size of 43.125 Mb, with 9960 unique protein-coding genes. The novel genomic resources allow improved genomic comparisons among the most important pathogens belonging to the Monilinia genus, with the aim being to improve the knowledge of their plant-pathogen interactions, population biology, and control.}, } @article {pmid30352623, year = {2018}, author = {Benler, S and Cobián-Güemes, AG and McNair, K and Hung, SH and Levi, K and Edwards, R and Rohwer, F}, title = {A diversity-generating retroelement encoded by a globally ubiquitous Bacteroides phage.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {191}, pmid = {30352623}, issn = {2049-2618}, abstract = {BACKGROUND: Diversity-generating retroelements (DGRs) are genetic cassettes that selectively mutate target genes to produce hypervariable proteins. First characterized in Bordetella bacteriophage BPP-1, the DGR creates a hypervariable phage tail fiber that enables host tropism switching. Subsequent surveys for DGRs conclude that the majority identified to date are bacterial or archaeal in origin. This work examines bacteriophage and bacterial genomes for novel phage-encoded DGRs.

RESULTS: This survey discovered 92 DGRs that were only found in phages exhibiting a temperate lifestyle. The majority of phage-encoded DGRs were identified as prophages in bacterial hosts from the phyla Bacteroidetes, Proteobacteria, and Firmicutes. Sequence reads from these previously unidentified prophages were present in viral metagenomes (viromes), indicating these prophages can produce functional viruses. Five phages possessed hypervariable proteins with structural similarity to the tail fiber of BPP-1, whereas the functions of the remaining DGR target proteins were unknown. A novel temperate phage that harbors a DGR cassette targeting a protein of unknown function was induced from Bacteroides dorei. This phage, here named Bacteroides dorei Hankyphage, lysogenizes 13 different Bacteroides species and was present in 34% and 21% of whole-community metagenomes and human-associated viromes, respectively.

CONCLUSIONS: Here, the number of known DGR-containing phages is increased from four to 92. All of these phages exhibit a temperate lifestyle, including a cosmopolitan human-associated phage. Targeted hypervariation by temperate phages may be a ubiquitous mechanism underlying phage-bacteria interaction in the human microbiome.}, } @article {pmid30352616, year = {2018}, author = {Taylor, I and Walker, JC}, title = {Transcriptomic evidence for distinct mechanisms underlying abscission deficiency in the Arabidopsis mutants haesa/haesa-like 2 and nevershed.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {754}, pmid = {30352616}, issn = {1756-0500}, abstract = {OBJECTIVE: In Arabidopsis, the abscission of floral organs is regulated by two related receptor-like protein kinases, HAESA and HAESA-like 2 (HAE/HSL2). Signaling by HAE/HSL2 leads to expression of genes encoding secreted cell wall remodeling and hydrolase enzymes. hae hsl2 mutants fail to induce expression of these genes and retain floral organs indefinitely. Mutants in the gene NEVERSHED (NEV) also fail to abscise floral organs and phenotypically resemble hae hsl2. NEV encodes an ADP-ribosylation factor GTPase-activating protein that localizes to the trans-Golgi network and early endosome. nev displays altered Golgi morphology and aberrations in vesicular trafficking. The mechanism by which nev fails to abscise is presently unknown. It has been hypothesized that nev fails to activate HAE/HSL2 signaling. In this study we use RNA-Sequencing to test this hypothesis.

RESULTS: We show that the transcriptional alterations in hae hsl2 and nev are highly divergent. hae hsl2 displays a clear reduction in expression of genes associated with cell wall remodeling and pectin degradation, while nev displays vast transcriptional changes associated with response to pathogens. These results suggest that the mechanism of the defect between hae hsl2 and nev are distinct.}, } @article {pmid30352614, year = {2018}, author = {Mojtabanezhad Shariatpanahi, A and Rokni, P and Shahabi, E and Varshoee Tabrizi, F and Kerachian, MA}, title = {Simple and cost-effective laboratory methods to evaluate and validate cell-free DNA isolation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {757}, pmid = {30352614}, issn = {1756-0500}, support = {Grant No. 961272//Mashhad University of Medical Sciences/ ; }, abstract = {OBJECTIVE: In the present study, we investigated different simple and cost effective methods to evaluate and validate cell free DNA (cfDNA) isolation. The ability of the QIAamp DNA Blood Mini Kit method to extract cfDNA was assessed by several approaches, including purification of endogenous cfDNA and exogenous spike-in control material, prior to plasma extraction, and followed by quantitative-PCR.

RESULTS: Using QIAamp DNA Blood Mini kit, nearly 27% (380 bp) to 35% (173 bp) cfDNA was recovered with a higher recovery of smaller size cfDNA (173 bp) in comparison to larger ones (380 bp). These simple laboratory methods can be used to assess the efficiency of any cfDNA isolation method.}, } @article {pmid30352612, year = {2018}, author = {Massey, WV and Ku, B and Stellino, MB}, title = {Observations of playground play during elementary school recess.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {755}, pmid = {30352612}, issn = {1756-0500}, abstract = {OBJECTIVE: The purpose of the current study was to examine reliability and validity evidence for an observational measure of playground play during recess. Observational data of what children played at recess were collected at 236 recess sessions across 26 urban elementary schools. An inductive content analysis of children's type of play and activity engagement during recess was conducted to categorize activities. Inter-rater reliability of observations was assessed at 49 points that spanned 22 unique recess periods at four different schools. Reliability data were collected during the winter and spring seasons. A multivariate analysis of variance was conducted to examine differences in play and activity patterns between genders, and between schools implementing recess interventions (e.g., structured play environment) and schools with no recess intervention.

RESULTS: Results of the content analysis yielded eight playground play and activity categories, all with high levels of inter-rater reliability (ICCs > .90). Significant differences in children's play and activity patterns emerged between genders and across recess intervention conditions. Engagement in 'sports and organized activities' and 'non-engagement in play' contributed most to the separation between boys and girls, while 'non-engagement in play' contributed most to the separation between recess intervention and non-intervention schools.}, } @article {pmid30352611, year = {2018}, author = {Earl, JP and Adappa, ND and Krol, J and Bhat, AS and Balashov, S and Ehrlich, RL and Palmer, JN and Workman, AD and Blasetti, M and Sen, B and Hammond, J and Cohen, NA and Ehrlich, GD and Mell, JC}, title = {Species-level bacterial community profiling of the healthy sinonasal microbiome using Pacific Biosciences sequencing of full-length 16S rRNA genes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {190}, pmid = {30352611}, issn = {2049-2618}, support = {U01 DK082316/DK/NIDDK NIH HHS/United States ; R01 DC013588/DC/NIDCD NIH HHS/United States ; R01 DC002148/DC/NIDCD NIH HHS/United States ; }, abstract = {BACKGROUND: Pan-bacterial 16S rRNA microbiome surveys performed with massively parallel DNA sequencing technologies have transformed community microbiological studies. Current 16S profiling methods, however, fail to provide sufficient taxonomic resolution and accuracy to adequately perform species-level associative studies for specific conditions. This is due to the amplification and sequencing of only short 16S rRNA gene regions, typically providing for only family- or genus-level taxonomy. Moreover, sequencing errors often inflate the number of taxa present. Pacific Biosciences' (PacBio's) long-read technology in particular suffers from high error rates per base. Herein, we present a microbiome analysis pipeline that takes advantage of PacBio circular consensus sequencing (CCS) technology to sequence and error correct full-length bacterial 16S rRNA genes, which provides high-fidelity species-level microbiome data.

RESULTS: Analysis of a mock community with 20 bacterial species demonstrated 100% specificity and sensitivity with regard to taxonomic classification. Examination of a 250-plus species mock community demonstrated correct species-level classification of > 90% of taxa, and relative abundances were accurately captured. The majority of the remaining taxa were demonstrated to be multiply, incorrectly, or incompletely classified. Using this methodology, we examined the microgeographic variation present among the microbiomes of six sinonasal sites, by both swab and biopsy, from the anterior nasal cavity to the sphenoid sinus from 12 subjects undergoing trans-sphenoidal hypophysectomy. We found greater variation among subjects than among sites within a subject, although significant within-individual differences were also observed. Propiniobacterium acnes (recently renamed Cutibacterium acnes) was the predominant species throughout, but was found at distinct relative abundances by site.

CONCLUSIONS: Our microbial composition analysis pipeline for single-molecule real-time 16S rRNA gene sequencing (MCSMRT, https://github.com/jpearl01/mcsmrt) overcomes deficits of standard marker gene-based microbiome analyses by using CCS of entire 16S rRNA genes to provide increased taxonomic and phylogenetic resolution. Extensions of this approach to other marker genes could help refine taxonomic assignments of microbial species and improve reference databases, as well as strengthen the specificity of associations between microbial communities and dysbiotic states.}, } @article {pmid30352610, year = {2018}, author = {Vorontsov, IE and Fedorova, AD and Yevshin, IS and Sharipov, RN and Kolpakov, FA and Makeev, VJ and Kulakovskiy, IV}, title = {Genome-wide map of human and mouse transcription factor binding sites aggregated from ChIP-Seq data.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {756}, pmid = {30352610}, issn = {1756-0500}, support = {17-74-10188//Russian Science Foundation/ ; 14-50-00060//Russian Science Foundation/ ; Program in molecular//Russian Academy of Sciences/ ; cellular biology//Russian Academy of Sciences/ ; Systems Biology Fellowship//Skolkovo Institute of Science and Technology/ ; Program of fundamental research for state academies for 2013-2020 years (No 01201363825)//Ministry of Education and Science of the Russian Federation/ ; }, abstract = {OBJECTIVES: Mammalian genomics studies, especially those focusing on transcriptional regulation, require information on genomic locations of regulatory regions, particularly, transcription factor (TF) binding sites. There are plenty of published ChIP-Seq data on in vivo binding of transcription factors in different cell types and conditions. However, handling of thousands of separate data sets is often impractical and it is desirable to have a single global map of genomic regions potentially bound by a particular TF in any of studied cell types and conditions.

DATA DESCRIPTION: Here we report human and mouse cistromes, the maps of genomic regions that are routinely identified as TF binding sites, organized by TF. We provide cistromes for 349 mouse and 599 human TFs. Given a TF, its cistrome regions are supported by evidence from several ChIP-Seq experiments or several computational tools, and, as an optional filter, contain occurrences of sequence motifs recognized by the TF. Using the cistrome, we provide an annotation of TF binding sites in the vicinity of human and mouse transcription start sites. This information is useful for selecting potential gene targets of transcription factors and detecting co-regulated genes in differential gene expression data.}, } @article {pmid30352578, year = {2018}, author = {Hühne, R and Kessler, V and Fürstberger, A and Kühlwein, S and Platzer, M and Sühnel, J and Lausser, L and Kestler, HA}, title = {3D Network exploration and visualisation for lifespan data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {390}, pmid = {30352578}, issn = {1471-2105}, support = {JenAge//Bundesministerium für Forschung und Technologie/ ; SyStaR//Bundesministerium für Forschung und Technologie/ ; SFB 1074, Project Z1//Deutsche Forschungsgemeinschaft/ ; e:Med, SYMBOL-HF, ID 01ZX1407A//Bundesministerium für Forschung und Technologie/ ; CAM-PaC, 602783//FP7 Ideas: European Research Council/ ; }, mesh = {Aging/*genetics ; *Computer Graphics ; *Databases, Factual ; Gene Ontology ; *Gene Regulatory Networks ; Humans ; Longevity/genetics ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: The Ageing Factor Database AgeFactDB contains a large number of lifespan observations for ageing-related factors like genes, chemical compounds, and other factors such as dietary restriction in different organisms. These data provide quantitative information on the effect of ageing factors from genetic interventions or manipulations of lifespan. Analysis strategies beyond common static database queries are highly desirable for the inspection of complex relationships between AgeFactDB data sets. 3D visualisation can be extremely valuable for advanced data exploration.

RESULTS: Different types of networks and visualisation strategies are proposed, ranging from basic networks of individual ageing factors for a single species to complex multi-species networks. The augmentation of lifespan observation networks by annotation nodes, like gene ontology terms, is shown to facilitate and speed up data analysis. We developed a new Javascript 3D network viewer JANet that provides the proposed visualisation strategies and has a customised interface for AgeFactDB data. It enables the analysis of gene lists in combination with AgeFactDB data and the interactive visualisation of the results.

CONCLUSION: Interactive 3D network visualisation allows to supplement complex database queries by a visually guided exploration process. The JANet interface allows gaining deeper insights into lifespan data patterns not accessible by common database queries alone. These concepts can be utilised in many other research fields.}, } @article {pmid30352567, year = {2018}, author = {Segura, A and Bertoni, M and Auffret, P and Klopp, C and Bouchez, O and Genthon, C and Durand, A and Bertin, Y and Forano, E}, title = {Transcriptomic analysis reveals specific metabolic pathways of enterohemorrhagic Escherichia coli O157:H7 in bovine digestive contents.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {766}, pmid = {30352567}, issn = {1471-2164}, support = {23000731//INRA-Région Auvergne/ ; ANR-10-INBS-09//ANR Investissement d'Avenir/ ; }, abstract = {BACKGROUND: The cattle gastrointestinal tract (GIT) is the main enterohemorrhagic Escherichia coli (EHEC) reservoir. In order to identify nutrients required for the survival or multiplication of EHEC in the bovine GIT, we compared the transcriptomes of the EHEC O157:H7 reference strain EDL933 cultured in vitro in bovine digestive contents (DCs) (rumen, small intestine and rectum) using RNA-sequencing.

RESULTS: Gene expression profiles showed that EHEC EDL933 activated common but also specific metabolic pathways to survive in the different bovine DCs. Mucus-derived carbohydrates seem important in EHEC nutrition in posterior DCs (small intestine and rectum) but not in rumen content. Additional carbohydrates (xylose, ribose, mannitol, galactitol) as well as gluconeogenic substrates (aspartate, serine, glycerol) would also be used by EHEC as carbon and/or nitrogen sources all along the bovine GIT including the rumen. However, xylose, GalNac, ribose and fucose transport and/or assimilation encoding genes were over-expressed during incubation in rectum content compared with rumen and intestine contents, and genes coding for maltose transport were only induced in rectum. This suggests a role for these carbohydrates in the colonization of the cattle rectum, considered as the major site for EHEC multiplication. In contrast, the transcription of the genes associated with the assimilation of ethanolamine, an important nitrogen source for EHEC, was poorly induced in EHEC growing in rectum content, suggesting that ethanolamine is mainly assimilated in the cattle rumen and small intestine. Respiratory flexibility would also be required for EHEC survival because of the redundancy of dehydrogenases and reductases simultaneously induced in the bovine DCs, probably in response to the availability of electron donors and acceptors.

CONCLUSION: EHEC EDL933 showed a high flexibility in the activation of genes involved in respiratory pathways and assimilation of carbon and nitrogen sources, most of them from animal origin. This may allow the bacterium to adapt and survive in the various bovine GIT compartments. Obtaining a better understanding of EHEC physiology in bovine GIT is a key step to ultimately propose strategies to limit EHEC carriage and shedding by cattle.}, } @article {pmid30352561, year = {2018}, author = {Straube, N and Li, C and Mertzen, M and Yuan, H and Moritz, T}, title = {A phylogenomic approach to reconstruct interrelationships of main clupeocephalan lineages with a critical discussion of morphological apomorphies.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {158}, pmid = {30352561}, issn = {1471-2148}, mesh = {Animals ; Base Sequence ; Bone and Bones/anatomy & histology ; DNA, Concatenated/genetics ; Fishes/*anatomy & histology/classification/*genetics ; *Genomics ; *Phylogeny ; }, abstract = {BACKGROUND: Previous molecular studies on the phylogeny and classification of clupeocephalan fishes revealed numerous new taxonomic entities. For re-analysing these taxa, we perform target gene capturing and subsequent next generation sequencing of putative ortholog exons of major clupeocephalan lineages. Sequence information for the RNA bait design was derived from publicly available genomes of bony fishes. Newly acquired sequence data comprising > 800 exon sequences was subsequently used for phylogenetic reconstructions.

RESULTS: Our results support monophyletic Otomorpha comprising Alepocephaliformes. Within Ostariophysi, Gonorynchiformes are sister to a clade comprising Cypriniformes, Characiformes, Siluriformes and Gymnotiformes, where the interrelationships of Characiformes, Siluriformes and Gymnotiformes remain enigmatic. Euteleosts comprise four major clades: Lepidogalaxiiformes, Protacanthopterygii, Stomiatii, and Galaxiiformes plus Neoteleostei. The monotypic Lepidogalaxiiformes form the sister-group to all remaining euteleosts. Protacanthopterygii, comprising Argentini-, Esoci- and Salmoniformes, is sister to Stomiatii (Osmeriformes and Stomiatiformes) and Galaxiiformes plus Neoteleostei.

CONCLUSIONS: Several proposed monophyla defined by morphological apomorphies within the Clupeocephalan phylogeny are confirmed by the phylogenetic estimates presented herein. However, other morphologically described groups cannot be reconciled with molecular phylogenies. Thus, numerous morphological apomoprhies of supposed monophyla are called into question. The interpretation of suggested morphological synapomorphies of otomorph fishes is strongly affected by the inclusion of deep-sea inhabiting, and to that effect morphologically adapted Alepocephaliformes. Our revision of these potential synapomorphies, in the context that Alepocephaliformes are otomorph fishes, reveals that only a single character of the total nine characters proposed as synapomorphic for the group is clearly valid for all otomorphs. Three further characters remain possible apomorphies since their status remains unclear in the deep-sea adapted Alepocephaliformes showing developmental lag and lacking a swim bladder. Further, our analysis places Galaxiiformes as sister group to neoteleosts, which contradicts some previous molecular phylogenetic studies. This needs further investigation from a morphological perspective, as suggested synapomophies for several euteleostean lineages are challenged or still lacking. For the verification of results presented herein, a denser phylogenomic-level taxon sampling should be applied.}, } @article {pmid30352553, year = {2018}, author = {Fritsch, TE and Siqueira, FM and Schrank, IS}, title = {Global analysis of sRNA target genes in Mycoplasma hyopneumoniae.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {767}, pmid = {30352553}, issn = {1471-2164}, support = {23038.010041/2013-13//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, abstract = {BACKGROUND: Small RNAs (sRNAs) are noncoding molecules that regulate different cellular activities in several bacteria. The role of sRNAs in gene expression regulation is poorly characterized in the etiological agent of porcine enzootic pneumonia Mycoplasma hyopneumoniae. We performed a global analysis of the sRNAs, sRNA target genes and regulatory elements previously identified in their genome and analyzed the expression of some sRNAs and their target genes by quantitative RT-PCR (qPCR) in three different culture conditions.

RESULTS: Seven of the 145 sRNA target genes are organized as monocistronic genes (mCs) while the other 138 sRNA target genes are organized into transcriptional units (TU). The identification of transcriptional regulatory elements (promoter motif, DNA repeat sequence or intrinsic terminator) was verified in 116 of the 145 sRNA target genes. Moreover, the 29 sRNA target genes without regulatory elements revealed the presence of at least one regulatory element in the boundaries of the TU or in other internal genes of the TU. We verified that 16 sRNAs showed differential expression, seven in heat shock condition and 14 in oxidative stress condition. Analysis of the differential expression of the sRNA target genes showed that the tested sRNAs possibly regulate gene expression. The sRNA target genes were up- or down-regulated possibly in response to sRNA only under oxidative stress condition. Moreover, the sRNA target genes are involved in diverse processes of the cell, some of which could be linked to transcription processes and cell homeostasis.

CONCLUSION: Our results indicate that bacterial sRNAs could regulate a number of targets with various outcomes, and different correlations between the levels of sRNA transcripts and their target gene mRNAs were found, which suggest that the regulation of gene expression via sRNAs may play an important role in mycoplasma.}, } @article {pmid30352551, year = {2018}, author = {Quan, S and Niu, J and Zhou, L and Xu, H and Ma, L and Qin, Y}, title = {Identification and characterization of NF-Y gene family in walnut (Juglans regia L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {255}, pmid = {30352551}, issn = {1471-2229}, support = {30560090//National Natural Science Foundation of China/ ; }, mesh = {CCAAT-Binding Factor/*genetics/metabolism ; Flowers/genetics ; Gene Expression Regulation, Plant ; Genome, Plant ; Juglans/*genetics ; Phylogeny ; Plant Leaves/genetics ; Plant Proteins/*genetics/metabolism ; Protein Interaction Maps ; }, abstract = {BACKGROUND: The eukaryotic transcription factor NF-Y (which consists of NF-YA, NF-YB and NF-YC subunits) is involved in many important plant development processes. There are many reports about the NF-Y family in Arabidopsis and other plant species. However, there are no reports about the NF-Y family in walnut (Juglans regia L.).

RESULTS: Thirty-three walnut NF-Y genes (JrNF-Ys) were identified and mapped on the walnut genome. The JrNF-Y gene family consisted of 17 NF-YA genes, 9 NF-YB genes, and 7 NF-YC genes. The structural features of the JrNF-Y genes were investigated by comparing their evolutionary relationship and motif distributions. The comparisons indicated the NF-Y gene structure was both conserved and altered during evolution. Functional prediction and protein interaction analysis were performed by comparing the JrNF-Y protein structure with that in Arabidopsis. Two differentially expressed JrNF-Y genes were identified. Their expression was compared with that of three JrCOs and two JrFTs using quantitative real-time PCR (qPCR). The results revealed that the expression of JrCO2 was positively correlated with the expression of JrNF-YA11 and JrNF-YA12. In contrast, JrNF-CO1 and JrNF-YA12 were negatively correlated.

CONCLUSIONS: Thirty-three JrNF-Ys were identified and their evolutionary, structure, biological function and expression pattern were analyzed. Two of the JrNF-Ys were screened out, their expression was differentially expressed in different development periods of female flower buds, and in different tissues (female flower buds and leaf buds). Based on prediction and experimental data, JrNF-Ys may be involved in flowering regulation by co-regulate the expression of flowering genes with other transcription factors (TFs). The results of this study may make contribution to the further investigation of JrNF-Y family.}, } @article {pmid30352217, year = {2018}, author = {Gao, X and Xie, XJ and Hsu, FN and Li, X and Liu, M and Hemba-Waduge, RU and Xu, W and Ji, JY}, title = {CDK8 mediates the dietary effects on developmental transition in Drosophila.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {62-70}, pmid = {30352217}, issn = {1095-564X}, support = {R01 DK095013/DK/NIDDK NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; }, abstract = {The complex interplay between genetic and environmental factors, such as diet and lifestyle, defines the initiation and progression of multifactorial diseases, including cancer, cardiovascular and metabolic diseases, and neurological disorders. Given that most of the studies have been performed in controlled experimental settings to ensure the consistency and reproducibility, the impacts of environmental factors, such as dietary perturbation, on the development of animals with different genotypes and the pathogenesis of these diseases remain poorly understood. By analyzing the cdk8 and cyclin C (cycC) mutant larvae in Drosophila, we have previously reported that the CDK8-CycC complex coordinately regulates lipogenesis by repressing dSREBP (sterol regulatory element-binding protein)-activated transcription and developmental timing by activating EcR (ecdysone receptor)-dependent gene expression. Here we report that dietary nutrients, particularly proteins and carbohydrates, modulate the developmental timing through the CDK8/CycC/EcR pathway. We observed that cdk8 and cycC mutants are sensitive to the levels of dietary proteins and seven amino acids (arginine, glutamine, isoleucine, leucine, methionine, threonine, and valine). Those mutants are also sensitive to dietary carbohydrates, and they are more sensitive to monosaccharides than disaccharides. These results suggest that CDK8-CycC mediates the dietary effects on lipid metabolism and developmental timing in Drosophila larvae.}, } @article {pmid30352216, year = {2018}, author = {Olesnicky, EC and Antonacci, S and Popitsch, N and Lybecker, MC and Titus, MB and Valadez, R and Derkach, PG and Marean, A and Miller, K and Mathai, SK and Killian, DJ}, title = {Shep interacts with posttranscriptional regulators to control dendrite morphogenesis in sensory neurons.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {116-128}, doi = {10.1016/j.ydbio.2018.09.022}, pmid = {30352216}, issn = {1095-564X}, support = {R25 NS080685/NS/NINDS NIH HHS/United States ; }, abstract = {RNA binding proteins (RBPs) mediate posttranscriptional gene regulatory events throughout development. During neurogenesis, many RBPs are required for proper dendrite morphogenesis within Drosophila sensory neurons. Despite their fundamental role in neuronal morphogenesis, little is known about the molecular mechanisms in which most RBPs participate during neurogenesis. In Drosophila, alan shepard (shep) encodes a highly conserved RBP that regulates dendrite morphogenesis in sensory neurons. Moreover, the C. elegans ortholog sup-26 has also been implicated in sensory neuron dendrite morphogenesis. Nonetheless, the molecular mechanism by which Shep/SUP-26 regulate dendrite development is not understood. Here we show that Shep interacts with the RBPs Trailer Hitch (Tral), Ypsilon schachtel (Yps), Belle (Bel), and Poly(A)-Binding Protein (PABP), to direct dendrite morphogenesis in Drosophila sensory neurons. Moreover, we identify a conserved set of Shep/SUP-26 target RNAs that include regulators of cell signaling, posttranscriptional gene regulators, and known regulators of dendrite development.}, } @article {pmid30351420, year = {2018}, author = {Aguilar-Rodríguez, J and Wagner, A}, title = {Metabolic Determinants of Enzyme Evolution in a Genome-Scale Bacterial Metabolic Network.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3076-3088}, pmid = {30351420}, issn = {1759-6653}, abstract = {Different genes and proteins evolve at very different rates. To identify the factors that explain these differences is an important aspect of research in molecular evolution. One such factor is the role a protein plays in a large molecular network. Here, we analyze the evolutionary rates of enzyme-coding genes in the genome-scale metabolic network of Escherichia coli to find the evolutionary constraints imposed by the structure and function of this complex metabolic system. Central and highly connected enzymes appear to evolve more slowly than less connected enzymes, but we find that they do so as a by-product of their high abundance, and not because of their position in the metabolic network. In contrast, enzymes catalyzing reactions with high metabolic flux-high substrate to product conversion rates-evolve slowly even after we account for their abundance. Moreover, enzymes catalyzing reactions that are difficult to by-pass through alternative pathways, such that they are essential in many different genetic backgrounds, also evolve more slowly. Our analyses show that an enzyme's role in the function of a metabolic network affects its evolution more than its place in the network's structure. They highlight the value of a system-level perspective for studies of molecular evolution.}, } @article {pmid30351396, year = {2018}, author = {Yu, G and Lam, TT and Zhu, H and Guan, Y}, title = {Two Methods for Mapping and Visualizing Associated Data on Phylogeny Using Ggtree.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {3041-3043}, pmid = {30351396}, issn = {1537-1719}, support = {HHSN272201400006C/AI/NIAID NIH HHS/United States ; }, abstract = {Ggtree is a comprehensive R package for visualizing and annotating phylogenetic trees with associated data. It can also map and visualize associated external data on phylogenies with two general methods. Method 1 allows external data to be mapped on the tree structure and used as visual characteristic in tree and data visualization. Method 2 plots the data with the tree side by side using different geometric functions after reordering the data based on the tree structure. These two methods integrate data with phylogeny for further exploration and comparison in the evolutionary biology context. Ggtree is available from http://www.bioconductor.org/packages/ggtree.}, } @article {pmid30351271, year = {2018}, author = {Yan, R and Fu, Y and Liu, D and Jiang, S and Ju, H and Guo, X and Guo, X and Wang, X and Zhang, J and Xiang, W}, title = {Arthrobacter silvisoli sp. nov., isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3892-3896}, doi = {10.1099/ijsem.0.003085}, pmid = {30351271}, issn = {1466-5034}, mesh = {Arthrobacter/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-positive, strictly aerobic strain, NEAU-SA1T, which showed a rod-coccus growth life cycle, was isolated from forest soil from Zhangjiajie, Hunan Province, China. The isolate grew at 10-40 °C (optimum 28 °C), at pH 5.0-10.0 (optimum pH 7.0) and in the presence of up to 5 % (w/v) NaCl, although NaCl was not required for growth. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NEAU-SA1T belonged to the genus Arthrobacter and was closely related to Arthrobacter cupressi DSM 24664T (98.1 % similarity). Average nucleotide identity values between NEAU-SA1T and A. cupressi DSM 24664T were 88.91 and 87.41 % by ANIm and ANIb analysis, respectively. The in silico DNA-DNA hybridization value between strain NEAU-SA1T and A. cupressi DSM 24664T was 34.20 %, again indicating they belong to different taxa. The genomic DNA G+C content was 66.74 mol%. The major cellular fatty acids (>10 %) were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and two unidentified glycolipids. The predominant menaquinone was MK-9(H2). The peptidoglycan type was A3α with an interpeptide bridge comprising l-Lys and l-Ala. Glucose, ribose and galactose were the whole-cell sugars. On the basis of morphological, physiological, biochemical and chemotaxonomic analysis, strain NEAU-SA1T was classified as representing a novel species in the genus Arthrobacter, for which the name Arthrobacter silvisoli sp. nov. is proposed. The type strain is NEAU-SA1T (=DSM 106716T=CCTCC AB 2017271T).}, } @article {pmid30351269, year = {2018}, author = {Lin, D and Chen, Y and Zhu, S and Yang, J and Chen, J}, title = {Alteromonas indica sp. nov., isolated from surface seawater from the Indian Ocean.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3881-3885}, doi = {10.1099/ijsem.0.003078}, pmid = {30351269}, issn = {1466-5034}, mesh = {Alteromonas/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Indian Ocean ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative bacterium, designated strain IO390401T, was isolated from a seawater sample from the sulphide region of the Indian Ocean. Phylogenetic trees based on 16S rRNA gene sequences showed that strain IO390401T is a member of the genus Alteromonas, sharing 97.0-97.4 % 16S rRNA gene sequence similarity with Alteromonas additaR10SW13T, A. stellipolaris LMG 21861T, A. naphthalenivorans JCM 17741T, A. gracilis 9a2T and A. australica H17T, and 94.8-96.8 % with the type strains of other species of the genus Alteromonas. Strain IO390401T contained ubiquinone-8 (Q-8) as the sole isoprenoid quinone, C16:0 and C16:1ω7c/C16:1ω6c as the dominant cellular fatty acids, and phosphatidylglycerol and phosphatidylethanolamine as the major polar lipids. The genome of strain IO390401T consists of a 4.4 Mb chromosome with a G+C content of 48.2 mol%. Average nucleotide identity values between strain IO390401T and the three closest phylogenetic neighbours, namely A. additaR10SW13T, A. stellipolaris LMG 21861T and A. naphthalenivorans JCM 17741T, were 70.5, 70.4 and 70.6 %, respectively, and the corresponding in silico DNA-DNA hybridization values were 20.6, 20.7 and 21.1 %. Phylogenetic distinctiveness and chemotaxonomic differences, together with phenotypic properties determined in this study, revealed that strain IO390401T could be differentiated from closely related species. It is therefore proposed as representing a novel species in the genus Alteromonas, for which the name Alteromonas indica sp. nov. is suggested. The type strain is IO390401T (=JCM 32638T=CGMCC 1.13554T=CCTCC AB 2018072T).}, } @article {pmid30351263, year = {2018}, author = {Meng, X and Lai, XH and Lu, S and Liu, S and Chen, C and Zhou, D and Yang, J and Jin, D and Xu, J}, title = {Actinomyces tangfeifanii sp. nov., isolated from the vulture Aegypius monachus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3701-3706}, doi = {10.1099/ijsem.0.003013}, pmid = {30351263}, issn = {1466-5034}, mesh = {Actinomyces/*classification/genetics/isolation & purification ; Animals ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Falconiformes/*microbiology ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rectum/microbiology ; Sequence Analysis, DNA ; }, abstract = {A novel, Gram-stain-positive, catalase-positive, non-spore-forming, short rod-shaped strain (VUL4_3T) was isolated from rectal swabs of Old World vultures (Aegypius monachus) from the Tibet-Qinghai Plateau, China. Based on the results of biochemical tests and 16S rRNA gene sequence comparison, strain VUL4_3T was determined to be a member of the genus Actinomyces that is closely related to the type strains of Actinomyces liubingyangii (97.7 % 16S rRNA gene sequence similarity) and Actinomyces marimammalium (96.5 %). Optimal growth occurred at 37 °C, pH 6-7 and with 1 % (w/v) NaCl. The typical major cellular fatty acids of strain VUL4_3T were C18 : 1ω9c, C16 : 0 and C18 : 0. The VUL4_3T genome contained 2 207 832 bp with an average G+C content of 51.9 mol%. DNA-DNA hybridization values between strain VUL4_3T and the above two species of the genus Actinomyces showed less than 32 % DNA-DNA relatedness, supporting a novel species status of strain VUL4_3T. Based on the phenotypic data and phylogenetic inference, the novel species Actinomycestangfeifanii sp. nov. is proposed. The type strain is VUL4_3T (=CGMCC 4.7369T=DSM 103436T).}, } @article {pmid30351261, year = {2018}, author = {Oren, A and Garrity, GM}, title = {List of new names and new combinations previously effectively, but not validly, published.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3379-3393}, doi = {10.1099/ijsem.0.003071}, pmid = {30351261}, issn = {1466-5034}, } @article {pmid30351260, year = {2018}, author = {Shetty, SA and Zuffa, S and Bui, TPN and Aalvink, S and Smidt, H and De Vos, WM}, title = {Reclassification of Eubacterium hallii as Anaerobutyricum hallii gen. nov., comb. nov., and description of Anaerobutyricum soehngenii sp. nov., a butyrate and propionate-producing bacterium from infant faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3741-3746}, doi = {10.1099/ijsem.0.003041}, pmid = {30351260}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Butyrates/metabolism ; DNA, Bacterial/genetics ; Eubacterium/*classification/metabolism ; Fatty Acids/chemistry ; Feces/*microbiology ; Humans ; Infant ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; Propionates/metabolism ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A bacterial strain designated L2-7T, phylogenetically related to Eubacterium hallii DSM 3353T, was previously isolated from infant faeces. The complete genome of strain L2-7T contains eight copies of the 16S rRNA gene with only 98.0-98.5 % similarity to the 16S rRNA gene of the previously described type strain E. hallii. The next closest validly described species is Anaerostipes hadrus DSM 3319T (90.7 % 16S rRNA gene similarity). A polyphasic taxonomic approach showed strain L2-7T to be a novel species, related to type strain E. hallii DSM 3353T. The experimentally observed DNA-DNA hybridization value between strain L2-7T and E. hallii DSM 3353T was 26.25 %, close to that calculated from the genomes (34.3 %). The G+C content of the chromosomal DNA of strain L2-7T was 38.6 mol%. The major fatty acids were C16 : 0, C16 : 1cis9 and a component with summed feature 10 (C18 : 1c11/t9/t6c). Strain L2-7T had higher amounts of C16 : 0 (30.6 %) compared to E. hallii DSM 3353T (19.5 %) and its membrane contained phosphatidylglycerol and phosphatidylethanolamine, which were not detected in E. hallii DSM 3353T. Furthermore, 16S rRNA gene phylogenetic analysis advocates that E. hallii DSM 3353T is misclassified, and its reclassification as a member of the family Lachnospiraceae is necessary. Using a polyphasic approach, we propose that E. hallii (=DSM 3353T=ATCC 27751T) be reclassified as the type strain of a novel genus Anaerobutyricum sp. nov., comb. nov. and we propose that strain L2-7T should be classified as a novel species, Anaerobutyricum soehngenii sp. nov. The type strain is L2-7T (=DSM 17630T=KCTC 15707T).}, } @article {pmid30349619, year = {2018}, author = {Yu, Z and Yang, G and Liu, X and Wang, Y and Zhuang, L and Zhou, S}, title = {Complete genome sequence of the nitrogen-fixing bacterium Azospirillum humicireducens type strain SgZ-5T.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {28}, pmid = {30349619}, issn = {1944-3277}, abstract = {The Azospirillum humicireducens strain SgZ-5T, belonging to the Order Rhodospirillales and the Family Rhodospirillaceae, was isolated from a microbial fuel cell inoculated with paddy soil. A previous work has shown that strain SgZ-5T was able to fix atmospheric nitrogen involved in plant growth promotion. Here we present the complete genome of A. humicireducens SgZ-5T, which consists of a circular chromosome and six plasmids with the total genome size of 6,834,379 bp and the average GC content of 67.55%. Genome annotations predicted 5969 protein coding and 85 RNA genes including 14 rRNA and 67 tRNA genes. By genomic analysis, we identified a complete set of genes that is potentially involved in nitrogen fixation and its regulation. This genome also harbors numerous genes that are likely responsible for phytohormones production. We anticipate that the A. humicireducens SgZ-5T genome will contribute insights into plant growth promoting properties of Azospirillum strains.}, } @article {pmid30349133, year = {2018}, author = {}, title = {When proteins stand on their heads for science.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {462}, doi = {10.1038/d41586-018-07102-9}, pmid = {30349133}, issn = {1476-4687}, } @article {pmid30349132, year = {2018}, author = {Fischer, G}, title = {Transforming the global food system.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {501-502}, doi = {10.1038/d41586-018-07094-6}, pmid = {30349132}, issn = {1476-4687}, } @article {pmid30349131, year = {2018}, author = {Abraham, M}, title = {Parrot patrol.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {499}, doi = {10.1038/d41586-018-07098-2}, pmid = {30349131}, issn = {1476-4687}, } @article {pmid30349130, year = {2018}, author = {Freeman, M}, title = {Ben Barres: neuroscience pioneer, gender champion.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {492}, doi = {10.1038/d41586-018-07109-2}, pmid = {30349130}, issn = {1476-4687}, } @article {pmid30349129, year = {2018}, author = {}, title = {Maize cob from prehistoric village reveals record-setting virus.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {462-463}, doi = {10.1038/d41586-018-07085-7}, pmid = {30349129}, issn = {1476-4687}, } @article {pmid30349128, year = {2018}, author = {}, title = {Why an elephant's tail is a feeble fly-swatter.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {463}, doi = {10.1038/d41586-018-07069-7}, pmid = {30349128}, issn = {1476-4687}, } @article {pmid30349127, year = {2018}, author = {}, title = {World's biggest plant shrinks as hungry deer move in.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {462}, doi = {10.1038/d41586-018-07066-w}, pmid = {30349127}, issn = {1476-4687}, } @article {pmid30349126, year = {2018}, author = {}, title = {A beetle's secret sauce prevents its diet of carrion from liquefying.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {462}, doi = {10.1038/d41586-018-07052-2}, pmid = {30349126}, issn = {1476-4687}, } @article {pmid30349125, year = {2018}, author = {}, title = {How the mighty Mekong River dug deep.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {463}, doi = {10.1038/d41586-018-07056-y}, pmid = {30349125}, issn = {1476-4687}, } @article {pmid30349124, year = {2018}, author = {}, title = {Cosmic bubble spawns one of the biggest galactic swarms ever seen.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {463}, doi = {10.1038/d41586-018-07028-2}, pmid = {30349124}, issn = {1476-4687}, } @article {pmid30349123, year = {2018}, author = {Bøggild, P}, title = {The war on fake graphene.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {502-503}, doi = {10.1038/d41586-018-06939-4}, pmid = {30349123}, issn = {1476-4687}, } @article {pmid30349122, year = {2018}, author = {Laird, DJ}, title = {How to lose your inheritance.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {497-498}, doi = {10.1038/d41586-018-06849-5}, pmid = {30349122}, issn = {1476-4687}, mesh = {Animals ; *Germ Cells ; *Heredity ; Mice ; Otx Transcription Factors ; }, } @article {pmid30349121, year = {2018}, author = {Penney, J and Tsai, LH}, title = {Elimination of senescent cells prevents neurodegeneration in mice.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {503-504}, doi = {10.1038/d41586-018-06677-7}, pmid = {30349121}, issn = {1476-4687}, mesh = {Animals ; *Cognitive Dysfunction ; Kinetics ; Mice ; *Neuroglia ; }, } @article {pmid30349119, year = {2018}, author = {Zink, F and Magnusdottir, DN and Magnusson, OT and Walker, NJ and Morris, TJ and Sigurdsson, A and Halldorsson, GH and Gudjonsson, SA and Melsted, P and Ingimundardottir, H and Kristmundsdottir, S and Alexandersson, KF and Helgadottir, A and Gudmundsson, J and Rafnar, T and Jonsdottir, I and Holm, H and Eyjolfsson, GI and Sigurdardottir, O and Olafsson, I and Masson, G and Gudbjartsson, DF and Thorsteinsdottir, U and Halldorsson, BV and Stacey, SN and Stefansson, K}, title = {Insights into imprinting from parent-of-origin phased methylomes and transcriptomes.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1542-1552}, doi = {10.1038/s41588-018-0232-7}, pmid = {30349119}, issn = {1546-1718}, abstract = {Imprinting is the preferential expression of one parental allele over the other. It is controlled primarily through differential methylation of cytosine at CpG dinucleotides. Here we combine 285 methylomes and 11,617 transcriptomes from peripheral blood samples with parent-of-origin phased haplotypes, to produce a new map of imprinted methylation and gene expression patterns across the human genome. We demonstrate how imprinted methylation is a continuous rather than a binary characteristic. We describe at high resolution the parent-of-origin methylation pattern at the 15q11.2 Prader-Willi/Angelman syndrome locus, with nearly confluent stochastic paternal methylation punctuated by 'spikes' of maternal methylation. We find examples of polymorphic imprinted methylation unrelated (at VTRNA2-1 and PARD6G) or related (at CHRNE) to nearby SNP genotypes. We observe RNA isoform-specific imprinted expression patterns suggestive of a methylation-sensitive transcriptional elongation block. Finally, we gain new insights into parent-of-origin-specific effects on phenotypes at the DLK1/MEG3 and GNAS loci.}, } @article {pmid30349118, year = {2018}, author = {Canela-Xandri, O and Rawlik, K and Tenesa, A}, title = {An atlas of genetic associations in UK Biobank.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1593-1599}, doi = {10.1038/s41588-018-0248-z}, pmid = {30349118}, issn = {1546-1718}, abstract = {Genome-wide association studies (GWAS) have identified many loci contributing to variation in complex traits, yet the majority of loci that contribute to the heritability of complex traits remain elusive. Large study populations with sufficient statistical power are required to detect the small effect sizes of the yet unidentified genetic variants. However, the analysis of huge cohorts, like UK Biobank, is challenging. Here, we present an atlas of genetic associations for 118 non-binary and 660 binary traits of 452,264 UK Biobank participants of European ancestry. Results are compiled in a publicly accessible database that allows querying genome-wide association results for 9,113,133 genetic variants, as well as downloading GWAS summary statistics for over 30 million imputed genetic variants (>23 billion phenotype-genotype pairs). Our atlas of associations (GeneATLAS, http://geneatlas.roslin.ed.ac.uk) will help researchers to query UK Biobank results in an easy and uniform way without the need to incur high computational costs.}, } @article {pmid30349117, year = {2018}, author = {Vesth, TC and Nybo, JL and Theobald, S and Frisvad, JC and Larsen, TO and Nielsen, KF and Hoof, JB and Brandl, J and Salamov, A and Riley, R and Gladden, JM and Phatale, P and Nielsen, MT and Lyhne, EK and Kogle, ME and Strasser, K and McDonnell, E and Barry, K and Clum, A and Chen, C and LaButti, K and Haridas, S and Nolan, M and Sandor, L and Kuo, A and Lipzen, A and Hainaut, M and Drula, E and Tsang, A and Magnuson, JK and Henrissat, B and Wiebenga, A and Simmons, BA and Mäkelä, MR and de Vries, RP and Grigoriev, IV and Mortensen, UH and Baker, SE and Andersen, MR}, title = {Investigation of inter- and intraspecies variation through genome sequencing of Aspergillus section Nigri.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1688-1695}, doi = {10.1038/s41588-018-0246-1}, pmid = {30349117}, issn = {1546-1718}, abstract = {Aspergillus section Nigri comprises filamentous fungi relevant to biomedicine, bioenergy, health, and biotechnology. To learn more about what genetically sets these species apart, as well as about potential applications in biotechnology and biomedicine, we sequenced 23 genomes de novo, forming a full genome compendium for the section (26 species), as well as 6 Aspergillus niger isolates. This allowed us to quantify both inter- and intraspecies genomic variation. We further predicted 17,903 carbohydrate-active enzymes and 2,717 secondary metabolite gene clusters, which we condensed into 455 distinct families corresponding to compound classes, 49% of which are only found in single species. We performed metabolomics and genetic engineering to correlate genotypes to phenotypes, as demonstrated for the metabolite aurasperone, and by heterologous transfer of citrate production to Aspergillus nidulans. Experimental and computational analyses showed that both secondary metabolism and regulation are key factors that are significant in the delineation of Aspergillus species.}, } @article {pmid30349116, year = {2018}, author = {Tome, JM and Tippens, ND and Lis, JT}, title = {Single-molecule nascent RNA sequencing identifies regulatory domain architecture at promoters and enhancers.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1533-1541}, doi = {10.1038/s41588-018-0234-5}, pmid = {30349116}, issn = {1546-1718}, support = {R01 GM025232/GM/NIGMS NIH HHS/United States ; T32 HD057854/HD/NICHD NIH HHS/United States ; UM1 HG009393/HG/NHGRI NIH HHS/United States ; }, abstract = {Eukaryotic RNA polymerase II (Pol II) has been found at both promoters and distal enhancers, suggesting additional functions beyond mRNA production. To understand this role, we sequenced nascent RNAs at single-molecule resolution to unravel the interplay between Pol II initiation, capping and pausing genome-wide. Our analyses identify two pause classes that are associated with different RNA capping profiles. More proximal pausing is associated with less complete capping, less elongation and a more enhancer-like complement of transcription factors than later pausing. Unexpectedly, transcription start sites (TSSs) are predominantly found in constellations composed of multiple divergent pairs. TSS clusters are intimately associated with precise arrays of nucleosomes and correspond with boundaries of transcription factor binding and chromatin modification at promoters and enhancers. TSS architecture is largely unchanged during the dramatic transcriptional changes induced by heat shock. Together, our results suggest that promoter- and enhancer-associated Pol II is a regulatory nexus for integrating information across TSS ensembles.}, } @article {pmid30349115, year = {2018}, author = {Kim, J and Piao, HL and Kim, BJ and Yao, F and Han, Z and Wang, Y and Xiao, Z and Siverly, AN and Lawhon, SE and Ton, BN and Lee, H and Zhou, Z and Gan, B and Nakagawa, S and Ellis, MJ and Liang, H and Hung, MC and You, MJ and Sun, Y and Ma, L}, title = {Long noncoding RNA MALAT1 suppresses breast cancer metastasis.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1705-1715}, pmid = {30349115}, issn = {1546-1718}, support = {R01 CA164346/CA/NCI NIH HHS/United States ; R01 CA166051/CA/NCI NIH HHS/United States ; R01 CA181029/CA/NCI NIH HHS/United States ; R01 CA181196/CA/NCI NIH HHS/United States ; R01 CA175486/CA/NCI NIH HHS/United States ; R01 CA190370/CA/NCI NIH HHS/United States ; R01 CA200703/CA/NCI NIH HHS/United States ; U24 CA209851/CA/NCI NIH HHS/United States ; }, abstract = {MALAT1 has previously been described as a metastasis-promoting long noncoding RNA (lncRNA). We show here, however, that targeted inactivation of the Malat1 gene in a transgenic mouse model of breast cancer, without altering the expression of its adjacent genes, promotes lung metastasis, and that this phenotype can be reversed by genetic add-back of Malat1. Similarly, knockout of MALAT1 in human breast cancer cells induces their metastatic ability, which is reversed by re-expression of Malat1. Conversely, overexpression of Malat1 suppresses breast cancer metastasis in transgenic, xenograft, and syngeneic models. Mechanistically, the MALAT1 lncRNA binds and inactivates the prometastatic transcription factor TEAD, preventing TEAD from associating with its co-activator YAP and target gene promoters. Moreover, MALAT1 levels inversely correlate with breast cancer progression and metastatic ability. These findings demonstrate that MALAT1 is a metastasis-suppressing lncRNA rather than a metastasis promoter in breast cancer, calling for rectification of the model for this highly abundant and conserved lncRNA.}, } @article {pmid30349114, year = {2018}, author = {Chu, T and Rice, EJ and Booth, GT and Salamanca, HH and Wang, Z and Core, LJ and Longo, SL and Corona, RJ and Chin, LS and Lis, JT and Kwak, H and Danko, CG}, title = {Chromatin run-on and sequencing maps the transcriptional regulatory landscape of glioblastoma multiforme.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1553-1564}, pmid = {30349114}, issn = {1546-1718}, support = {R01 GM025232/GM/NIGMS NIH HHS/United States ; R01 HG009309/HG/NHGRI NIH HHS/United States ; R37 GM025232/GM/NIGMS NIH HHS/United States ; }, abstract = {The human genome encodes a variety of poorly understood RNA species that remain challenging to identify using existing genomic tools. We developed chromatin run-on and sequencing (ChRO-seq) to map the location of RNA polymerase for almost any input sample, including samples with degraded RNA that are intractable to RNA sequencing. We used ChRO-seq to map nascent transcription in primary human glioblastoma (GBM) brain tumors. Enhancers identified in primary GBMs resemble open chromatin in the normal human brain. Rare enhancers that are activated in malignant tissue drive regulatory programs similar to the developing nervous system. We identified enhancers that regulate groups of genes that are characteristic of each known GBM subtype and transcription factors that drive them. Finally we discovered a core group of transcription factors that control the expression of genes associated with clinical outcomes. This study characterizes the transcriptional landscape of GBM and introduces ChRO-seq as a method to map regulatory programs that contribute to complex diseases.}, } @article {pmid30349095, year = {2018}, author = {Craine, JM and Elmore, AJ and Wang, L and Aranibar, J and Bauters, M and Boeckx, P and Crowley, BE and Dawes, MA and Delzon, S and Fajardo, A and Fang, Y and Fujiyoshi, L and Gray, A and Guerrieri, R and Gundale, MJ and Hawke, DJ and Hietz, P and Jonard, M and Kearsley, E and Kenzo, T and Makarov, M and Marañón-Jiménez, S and McGlynn, TP and McNeil, BE and Mosher, SG and Nelson, DM and Peri, PL and Roggy, JC and Sanders-DeMott, R and Song, M and Szpak, P and Templer, PH and Van der Colff, D and Werner, C and Xu, X and Yang, Y and Yu, G and Zmudczyńska-Skarbek, K}, title = {Isotopic evidence for oligotrophication of terrestrial ecosystems.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1735-1744}, doi = {10.1038/s41559-018-0694-0}, pmid = {30349095}, issn = {2397-334X}, abstract = {Human societies depend on an Earth system that operates within a constrained range of nutrient availability, yet the recent trajectory of terrestrial nitrogen (N) availability is uncertain. Examining patterns of foliar N concentrations and isotope ratios (δ15N) from more than 43,000 samples acquired over 37 years, here we show that foliar N concentration declined by 9% and foliar δ15N declined by 0.6-1.6‰. Examining patterns across different climate spaces, foliar δ15N declined across the entire range of mean annual temperature and mean annual precipitation tested. These results suggest declines in N supply relative to plant demand at the global scale. In all, there are now multiple lines of evidence of declining N availability in many unfertilized terrestrial ecosystems, including declines in δ15N of tree rings and leaves from herbarium samples over the past 75-150 years. These patterns are consistent with the proposed consequences of elevated atmospheric carbon dioxide and longer growing seasons. These declines will limit future terrestrial carbon uptake and increase nutritional stress for herbivores.}, } @article {pmid30349094, year = {2018}, author = {}, title = {Fungus focus.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1675}, doi = {10.1038/s41559-018-0721-1}, pmid = {30349094}, issn = {2397-334X}, } @article {pmid30349093, year = {2018}, author = {Milla, R and Bastida, JM and Turcotte, MM and Jones, G and Violle, C and Osborne, CP and Chacón-Labella, J and Sosinski, ÊE and Kattge, J and Laughlin, DC and Forey, E and Minden, V and Cornelissen, JHC and Amiaud, B and Kramer, K and Boenisch, G and He, T and Pillar, VD and Byun, C}, title = {Phylogenetic patterns and phenotypic profiles of the species of plants and mammals farmed for food.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1808-1817}, doi = {10.1038/s41559-018-0690-4}, pmid = {30349093}, issn = {2397-334X}, abstract = {The origins of agriculture were key events in human history, during which people came to depend for their food on small numbers of animal and plant species. However, the biological traits determining which species were domesticated for food provision, and which were not, are unclear. Here, we investigate the phylogenetic distribution of livestock and crops, and compare their phenotypic traits with those of wild species. Our results indicate that phylogenetic clustering is modest for crop species but more intense for livestock. Domesticated species explore a reduced portion of the phenotypic space occupied by their wild counterparts and have particular traits in common. For example, herbaceous crops are globally characterized by traits including high leaf nitrogen concentration and tall canopies, which make them fast-growing species and proficient competitors. Livestock species are relatively large mammals with low basal metabolic rates, which indicate moderate to slow life histories. Our study therefore reveals ecological differences in domestication potential between plants and mammals. Domesticated plants belong to clades with traits that are advantageous in intensively managed high-resource habitats, whereas domesticated mammals are from clades adapted to moderately productive environments. Combining comparative phylogenetic methods with ecologically relevant traits has proven useful to unravel the causes and consequences of domestication.}, } @article {pmid30349092, year = {2018}, author = {Lewitus, E and Bittner, L and Malviya, S and Bowler, C and Morlon, H}, title = {Clade-specific diversification dynamics of marine diatoms since the Jurassic.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1715-1723}, pmid = {30349092}, issn = {2397-334X}, abstract = {Diatoms are one of the most abundant and diverse groups of phytoplankton and play a major role in marine ecosystems and the Earth's biogeochemical cycles. Here we combine DNA metabarcoding data from the Tara Oceans expedition with palaeoenvironmental data and phylogenetic models of diversification to analyse the diversity dynamics of marine diatoms. We reveal a primary effect of variation in carbon dioxide partial pressure (pCO2) on early diatom diversification, followed by a major burst of diversification in the late Eocene epoch, after which diversification is chiefly affected by sea level, an influx of silica availability and competition with other planktonic groups. Our results demonstrate a remarkable heterogeneity of diversification dynamics across diatoms and suggest that a changing climate will favour some clades at the expense of others.}, } @article {pmid30349091, year = {2018}, author = {Qiu, B and Larsen, RS and Chang, NC and Wang, J and Boomsma, JJ and Zhang, G}, title = {Towards reconstructing the ancestral brain gene-network regulating caste differentiation in ants.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1782-1791}, pmid = {30349091}, issn = {2397-334X}, abstract = {Specialized queens and life-time unmated workers evolved once in the common ancestor of all ants, but whether caste development across ants continues to be at least partly regulated by a single core set of genes remains obscure. We analysed brain transcriptomes from five ant species (three subfamilies) and reconstructed the origins of genes with caste-biased expression. Ancient genes predating the Neoptera were more likely to regulate gyne (virgin queen) phenotypes, while the caste differentiation roles of younger, ant-lineage-specific genes varied. Transcriptome profiling showed that the ancestral network for caste-specific gene regulation has been maintained, but that signatures of common ancestry are obscured by later modifications. Adjusting for such differences, we identified a core gene-set that: (1) consistently displayed similar directions and degrees of caste-differentiated expression; and (2) have mostly not been reported as being involved in caste differentiation. These core regulatory genes exist in the genomes of ant species that secondarily lost the queen caste, but expression differences for reproductive and sterile workers are minor and similar to social paper wasps that lack differentiated castes. Many caste-biased ant genes have caste-differentiated expression in honeybees, but directions of caste bias were uncorrelated, as expected when permanent castes evolved independently in both lineages.}, } @article {pmid30349090, year = {2018}, author = {Ban, NC and Frid, A and Reid, M and Edgar, B and Shaw, D and Siwallace, P}, title = {Incorporate Indigenous perspectives for impactful research and effective management.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1680-1683}, doi = {10.1038/s41559-018-0706-0}, pmid = {30349090}, issn = {2397-334X}, } @article {pmid30349089, year = {2018}, author = {Kocher, SD}, title = {A toolkit for caste differentiation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1689-1690}, doi = {10.1038/s41559-018-0705-1}, pmid = {30349089}, issn = {2397-334X}, } @article {pmid30349083, year = {2018}, author = {Palleja, A and Mikkelsen, KH and Forslund, SK and Kashani, A and Allin, KH and Nielsen, T and Hansen, TH and Liang, S and Feng, Q and Zhang, C and Pyl, PT and Coelho, LP and Yang, H and Wang, J and Typas, A and Nielsen, MF and Nielsen, HB and Bork, P and Wang, J and Vilsbøll, T and Hansen, T and Knop, FK and Arumugam, M and Pedersen, O}, title = {Recovery of gut microbiota of healthy adults following antibiotic exposure.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1255-1265}, doi = {10.1038/s41564-018-0257-9}, pmid = {30349083}, issn = {2058-5276}, abstract = {To minimize the impact of antibiotics, gut microorganisms harbour and exchange antibiotics resistance genes, collectively called their resistome. Using shotgun sequencing-based metagenomics, we analysed the partial eradication and subsequent regrowth of the gut microbiota in 12 healthy men over a 6-month period following a 4-day intervention with a cocktail of 3 last-resort antibiotics: meropenem, gentamicin and vancomycin. Initial changes included blooms of enterobacteria and other pathobionts, such as Enterococcus faecalis and Fusobacterium nucleatum, and the depletion of Bifidobacterium species and butyrate producers. The gut microbiota of the subjects recovered to near-baseline composition within 1.5 months, although 9 common species, which were present in all subjects before the treatment, remained undetectable in most of the subjects after 180 days. Species that harbour β-lactam resistance genes were positively selected for during and after the intervention. Harbouring glycopeptide or aminoglycoside resistance genes increased the odds of de novo colonization, however, the former also decreased the odds of survival. Compositional changes under antibiotic intervention in vivo matched results from in vitro susceptibility tests. Despite a mild yet long-lasting imprint following antibiotics exposure, the gut microbiota of healthy young adults are resilient to a short-term broad-spectrum antibiotics intervention and their antibiotics resistance gene carriage modulates their recovery processes.}, } @article {pmid30349082, year = {2018}, author = {Aliprandini, E and Tavares, J and Panatieri, RH and Thiberge, S and Yamamoto, MM and Silvie, O and Ishino, T and Yuda, M and Dartevelle, S and Traincard, F and Boscardin, SB and Amino, R}, title = {Cytotoxic anti-circumsporozoite antibodies target malaria sporozoites in the host skin.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1224-1233}, doi = {10.1038/s41564-018-0254-z}, pmid = {30349082}, issn = {2058-5276}, abstract = {The circumsporozoite protein (CSP) is the major surface protein of malaria sporozoites (SPZs), the motile and invasive parasite stage inoculated in the host skin by infected mosquitoes. Antibodies against the central CSP repeats of different plasmodial species are known to block SPZ infectivity1-5, but the precise mechanism by which these effectors operate is not completely understood. Here, using a rodent Plasmodium yoelii malaria model, we show that sterile protection mediated by anti-P. yoelii CSP humoral immunity depends on the parasite inoculation into the host skin, where antibodies inhibit motility and kill P. yoelii SPZs via a characteristic 'dotty death' phenotype. Passive transfer of an anti-repeat monoclonal antibody (mAb) recapitulates the skin inoculation-dependent protection, in a complement- and Fc receptor γ-independent manner. This purified mAb also decreases motility and, notably, induces the dotty death of P. yoelii SPZs in vitro. Cytotoxicity is species-transcendent since cognate anti-CSP repeat mAbs also kill Plasmodium berghei and Plasmodium falciparum SPZs. mAb cytotoxicity requires the actomyosin motor-dependent translocation and stripping of the protective CSP surface coat, rendering the parasite membrane susceptible to the SPZ pore-forming-like protein secreted to wound and traverse the host cell membrane6. The loss of SPZ fitness caused by anti-P. yoelii CSP repeat antibodies is thus a dynamic process initiated in the host skin where SPZs either stop moving7, or migrate and traverse cells to progress through the host tissues7-9 at the eventual expense of their own life.}, } @article {pmid30349081, year = {2018}, author = {Sgro, GG and Costa, TRD and Cenens, W and Souza, DP and Cassago, A and Coutinho de Oliveira, L and Salinas, RK and Portugal, RV and Farah, CS and Waksman, G}, title = {Cryo-EM structure of the bacteria-killing type IV secretion system core complex from Xanthomonas citri.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1429-1440}, pmid = {30349081}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Type IV secretion (T4S) systems form the most common and versatile class of secretion systems in bacteria, capable of injecting both proteins and DNAs into host cells. T4S systems are typically composed of 12 components that form 2 major assemblies: the inner membrane complex embedded in the inner membrane and the core complex embedded in both the inner and outer membranes. Here we present the 3.3 Å-resolution cryo-electron microscopy model of the T4S system core complex from Xanthomonas citri, a phytopathogen that utilizes this system to kill bacterial competitors. An extensive mutational investigation was performed to probe the vast network of protein-protein interactions in this 1.13-MDa assembly. This structure expands our knowledge of the molecular details of T4S system organization, assembly and evolution.}, } @article {pmid30349080, year = {2018}, author = {Cartmell, A and Muñoz-Muñoz, J and Briggs, JA and Ndeh, DA and Lowe, EC and Baslé, A and Terrapon, N and Stott, K and Heunis, T and Gray, J and Yu, L and Dupree, P and Fernandes, PZ and Shah, S and Williams, SJ and Labourel, A and Trost, M and Henrissat, B and Gilbert, HJ}, title = {A surface endogalactanase in Bacteroides thetaiotaomicron confers keystone status for arabinogalactan degradation.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1314-1326}, pmid = {30349080}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Glycans are major nutrients for the human gut microbiota (HGM). Arabinogalactan proteins (AGPs) comprise a heterogenous group of plant glycans in which a β1,3-galactan backbone and β1,6-galactan side chains are conserved. Diversity is provided by the variable nature of the sugars that decorate the galactans. The mechanisms by which nutritionally relevant AGPs are degraded in the HGM are poorly understood. Here we explore how the HGM organism Bacteroides thetaiotaomicron metabolizes AGPs. We propose a sequential degradative model in which exo-acting glycoside hydrolase (GH) family 43 β1,3-galactanases release the side chains. These oligosaccharide side chains are depolymerized by the synergistic action of exo-acting enzymes in which catalytic interactions are dependent on whether degradation is initiated by a lyase or GH. We identified two GHs that establish two previously undiscovered GH families. The crystal structures of the exo-β1,3-galactanases identified a key specificity determinant and departure from the canonical catalytic apparatus of GH43 enzymes. Growth studies of Bacteroidetes spp. on complex AGP revealed 3 keystone organisms that facilitated utilization of the glycan by 17 recipient bacteria, which included B. thetaiotaomicron. A surface endo-β1,3-galactanase, when engineered into B. thetaiotaomicron, enabled the bacterium to utilize complex AGPs and act as a keystone organism.}, } @article {pmid30349002, year = {2018}, author = {Deng, Y and Yu, Y and Song, Y and Zhang, J and Wang, NZ and Sun, Z and Yi, Y and Wu, YZ and Wu, S and Zhu, J and Wang, J and Chen, XH and Zhang, Y}, title = {Gate-tunable room-temperature ferromagnetism in two-dimensional Fe3GeTe2.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {94-99}, doi = {10.1038/s41586-018-0626-9}, pmid = {30349002}, issn = {1476-4687}, abstract = {Materials research has driven the development of modern nano-electronic devices. In particular, research in magnetic thin films has revolutionized the development of spintronic devices1,2 because identifying new magnetic materials is key to better device performance and design. Van der Waals crystals retain their chemical stability and structural integrity down to the monolayer and, being atomically thin, are readily tuned by various kinds of gate modulation3,4. Recent experiments have demonstrated that it is possible to obtain two-dimensional ferromagnetic order in insulating Cr2Ge2Te6 (ref. 5) and CrI3 (ref. 6) at low temperatures. Here we develop a device fabrication technique and isolate monolayers from the layered metallic magnet Fe3GeTe2 to study magnetotransport. We find that the itinerant ferromagnetism persists in Fe3GeTe2 down to the monolayer with an out-of-plane magnetocrystalline anisotropy. The ferromagnetic transition temperature, Tc, is suppressed relative to the bulk Tc of 205 kelvin in pristine Fe3GeTe2 thin flakes. An ionic gate, however, raises Tc to room temperature, much higher than the bulk Tc. The gate-tunable room-temperature ferromagnetism in two-dimensional Fe3GeTe2 opens up opportunities for potential voltage-controlled magnetoelectronics7-11 based on atomically thin van der Waals crystals.}, } @article {pmid30348997, year = {2018}, author = {Bahcall, OG}, title = {UK Biobank - a new era in genomic medicine.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {737}, doi = {10.1038/s41576-018-0065-3}, pmid = {30348997}, issn = {1471-0064}, } @article {pmid30348880, year = {2018}, author = {Olofsson, J and Post, E}, title = {Effects of large herbivores on tundra vegetation in a changing climate, and implications for rewilding.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348880}, issn = {1471-2970}, abstract = {In contrast to that of the Pleistocene epoch, between approximately 2.6 million and 10 000 years before present, the extant community of large herbivores in Arctic tundra is species-poor predominantly due to human extinctions. We here discuss how this species-poor herbivore guild influences tundra ecosystems, especially in relation to the rapidly changing climate. We show that present herbivore assemblages have large effects on tundra ecosystem composition and function and suggest that the effect on thermophilic species expected to invade the tundra in a warmer climate is especially strong, and that herbivores slow ecosystem responses to climate change. We focus on the ability of herbivores to drive transitions between different vegetation states. One such transition is between tundra and forest. A second vegetation transition discussed is between grasslands and moss- and shrub-dominated tundra. Contemporary studies show that herbivores can drive such state shifts and that a more diverse herbivore assemblage would have even higher potential to do so. We conclude that even though many large herbivores, and especially the megaherbivores, are extinct, there is a potential to reintroduce large herbivores in many arctic locations, and that doing so would potentially reduce some of the unwanted effects of a warmer climate.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348879, year = {2018}, author = {Marjakangas, EL and Genes, L and Pires, MM and Fernandez, FAS and de Lima, RAF and de Oliveira, AA and Ovaskainen, O and Pires, AS and Prado, PI and Galetti, M}, title = {Estimating interaction credit for trophic rewilding in tropical forests.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348879}, issn = {1471-2970}, abstract = {Trophic rewilding has been suggested as a restoration tool to restore ecological interactions and reverse defaunation and its cascading effects on ecosystem functioning. One of the ecological processes that has been jeopardized by defaunation is animal-mediated seed dispersal. Here, we propose an approach that combines joint species distribution models with occurrence data and species interaction records to quantify the potential to restore seed-dispersal interactions through rewilding and apply it to the Atlantic Forest, a global biodiversity hotspot. Using this approach, we identify areas that should benefit the most from trophic rewilding and candidate species that could contribute to cash the credit of seed-dispersal interactions in a given site. We found that sites within large fragments bearing a great diversity of trees may have about 20 times as many interactions to be cashed through rewilding as small fragments in regions where deforestation has been pervasive. We also ranked mammal and bird species according to their potential to restore seed-dispersal interactions if reintroduced while considering the biome as a whole and at finer scales. The suggested approach can aid future conservation efforts in rewilding projects in defaunated tropical rainforests.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348878, year = {2018}, author = {Jepson, P and Schepers, F and Helmer, W}, title = {Governing with nature: a European perspective on putting rewilding principles into practice.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348878}, issn = {1471-2970}, abstract = {Academic interest in rewilding is moving from commentary to discussion on future research agendas. The quality of rewilding research design will be enhanced if it is informed by knowledge of the rewilding practice. Here, we describe the conceptual origins and six case study examples of a mode of rewilding that emerged in the Dutch Delta and is being promoted and supported by Rewilding Europe, an umbrella organization established in 2011. The case experiences presented help position this version of rewilding in relation to the US 3C's version and point towards a rewilding action philosophy characterized by pragmatic realism and pioneer projects around which multiactor networks interested in policy innovation and change form. We argue that scaling-up the models of rewilding presented is constrained by institutional cultures and will require innovations in conservation finance and business models. Nonetheless, we suggest that the expanding European Rewilding Network and associated facilities, such as the European Wildlife Bank, represent a valuable asset for natural science research, aimed at exploring the ecological impacts of grazing and the relationship between role of restored herbivore guilds and biotical expansion, and for social science research investigating concepts such as non-human agency and autonomy. Lastly, we ask applied scientists to view rewilding as an uncertain and unfolding conservation approach and to refrain from seeking to specify it as a management approach supporting the delivery of pre-determined targets and/or ideals. This is because such actions may constrain the transformative potential of rewilding practice.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348877, year = {2018}, author = {Torres, A and Fernández, N and Zu Ermgassen, S and Helmer, W and Revilla, E and Saavedra, D and Perino, A and Mimet, A and Rey-Benayas, JM and Selva, N and Schepers, F and Svenning, JC and Pereira, HM}, title = {Measuring rewilding progress.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348877}, issn = {1471-2970}, abstract = {Rewilding is emerging as a promising restoration strategy to enhance the conservation status of biodiversity and promote self-regulating ecosystems while re-engaging people with nature. Overcoming the challenges in monitoring and reporting rewilding projects would improve its practical implementation and maximize its conservation and restoration outcomes. Here, we present a novel approach for measuring and monitoring progress in rewilding that focuses on the ecological attributes of rewilding. We devised a bi-dimensional framework for assessing the recovery of processes and their natural dynamics through (i) decreasing human forcing on ecological processes and (ii) increasing ecological integrity of ecosystems. The rewilding assessment framework incorporates the reduction of material inputs and outputs associated with human management, as well as the restoration of natural stochasticity and disturbance regimes, landscape connectivity and trophic complexity. Furthermore, we provide a list of potential activities for increasing the ecological integrity after reviewing the evidence for the effectiveness of common restoration actions. For illustration purposes, we apply the framework to three flagship restoration projects in the Netherlands, Switzerland and Argentina. This approach has the potential to broaden the scope of rewilding projects, facilitate sound decision-making and connect the science and practice of rewilding.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348876, year = {2018}, author = {Bakker, ES and Svenning, JC}, title = {Trophic rewilding: impact on ecosystems under global change.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348876}, issn = {1471-2970}, } @article {pmid30348875, year = {2018}, author = {Derham, TT and Duncan, RP and Johnson, CN and Jones, ME}, title = {Hope and caution: rewilding to mitigate the impacts of biological invasions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348875}, issn = {1471-2970}, abstract = {Rewilding is a novel approach to ecological restoration. Trophic rewilding in particular aims to reinstate ecological functions, especially trophic interactions, through the introduction of animals. We consider the potential for trophic rewilding to address biological invasions. In this broad review, we note some of the important conceptual and ethical foundations of rewilding, including a focus on ecosystem function rather than composition, reliance on animal agency, and an appeal to an ethic of coexistence. Second, we use theory from invasion biology to highlight pathways by which rewilding might prevent or mitigate the impacts of an invasion, including increasing biotic resistance. Third, we use a series of case studies to illustrate how reintroductions can mitigate the impacts of invasions. These include reintroductions and positive management of carnivores and herbivores including European pine martens (Martes martes), Eurasian otters (Lutra lutra), dingoes (Canis dingo), Tasmanian devils (Sarcophilus harrisii) and tule elk (Cervus canadensis nannodes). Fourth, we consider the risk that rewilding may enable a biological invasion or aggravate its impacts. Lastly, we highlight lessons that rewilding science might take from invasion biology.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348874, year = {2018}, author = {Andriuzzi, WS and Wall, DH}, title = {Soil biological responses to, and feedbacks on, trophic rewilding.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348874}, issn = {1471-2970}, abstract = {Trophic rewilding-the (re)introduction of missing large herbivores and/or their predators-is increasingly proposed to restore biodiversity and biotic interactions, but its effects on soils have been largely neglected. The high diversity of soil organisms and the ecological functions they perform mean that the full impact of rewilding on ecosystems cannot be assessed considering only above-ground food webs. Here we outline current understanding on how animal species of rewilding interest affect soil structure, processes and communities, and how in turn soil biota may affect species above ground. We highlight considerable uncertainty in soil responses to and feedbacks on above-ground consumers, with potentially large implications for rewilding interactions with global change. For example, the impact of large herbivores on soil decomposers and plant-soil interactions could lead to reduced carbon sequestration, whereas herbivore interactions with keystone biota such as mycorrhizal fungi, dung beetles and bioturbators could promote native plants and ecosystem heterogeneity. Moreover, (re)inoculation of keystone soil biota could be considered as a strategy to meet some of the objectives of trophic rewilding. Overall, we call for the rewilding research community to engage more with soil ecology experts and consider above-ground-below-ground linkages as integral to assess potential benefits as well as pitfalls.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348873, year = {2018}, author = {Jarvie, S and Svenning, JC}, title = {Using species distribution modelling to determine opportunities for trophic rewilding under future scenarios of climate change.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348873}, issn = {1471-2970}, abstract = {Trophic rewilding, the (re)introduction of species to promote self-regulating biodiverse ecosystems, is a future-oriented approach to ecological restoration. In the twenty-first century and beyond, human-mediated climate change looms as a major threat to global biodiversity and ecosystem function. A critical aspect in planning trophic rewilding projects is the selection of suitable sites that match the needs of the focal species under both current and future climates. Species distribution models (SDMs) are currently the main tools to derive spatially explicit predictions of environmental suitability for species, but the extent of their adoption for trophic rewilding projects has been limited. Here, we provide an overview of applications of SDMs to trophic rewilding projects, outline methodological choices and issues, and provide a synthesis and outlook. We then predict the potential distribution of 17 large-bodied taxa proposed as trophic rewilding candidates and which represent different continents and habitats. We identified widespread climatic suitability for these species in the discussed (re)introduction regions under current climates. Climatic conditions generally remain suitable in the future, although some species will experience reduced suitability in parts of these regions. We conclude that climate change is not a major barrier to trophic rewilding as currently discussed in the literature.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348872, year = {2018}, author = {Tanentzap, AJ and Smith, BR}, title = {Unintentional rewilding: lessons for trophic rewilding from other forms of species introductions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348872}, issn = {1471-2970}, abstract = {Trophic rewilding involves adding species into ecosystems to restore extinct, top-down interactions, but limited quantitative data have prevented a systematic attempt to quantify its outcomes. Here, we exploit species introductions that have occurred for purposes other than restoration to inform trophic rewilding. We compiled 51 studies with 158 different responses of lower trophic levels to a species introduction that restored an extinct interaction, whether it intended to do so or not. Unintentional introductions were compared with checklists of extinct animals to identify potential analogues. Using the latest meta-analysis techniques, we found that the few cases of intentional rewilding had similar effects to unintentional rewilding, though there were large taxonomic and geographical biases. We also tested predictions from studies on trophic cascades about the factors that should influence rewilding. Unintentional rewilding was stronger where introduced consumers were non-invasive, but there was no effect of time that compared sites differed in introduction status, latitude or coevolution of responses with a taxonomically related analogue. Our study now shows that rewilding can reinstate extinct trophic interactions and highlights remaining data gaps that need closure to restore ecosystems across larger scales than has been previously possible.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348871, year = {2018}, author = {Willby, NJ and Law, A and Levanoni, O and Foster, G and Ecke, F}, title = {Rewilding wetlands: beaver as agents of within-habitat heterogeneity and the responses of contrasting biota.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348871}, issn = {1471-2970}, abstract = {Ecosystem engineers can increase biodiversity by creating novel habitat supporting species that would otherwise be absent. Their more routine activities further influence the biota occupying engineered habitats. Beavers are well-known for transforming ecosystems through dam building and are therefore increasingly being used for habitat restoration, adaptation to climate extremes and in long-term rewilding. Abandoned beaver ponds (BP) develop into meadows or forested wetlands that differ fundamentally from other terrestrial habitats and thus increase landscape diversity. Active BP, by contrast, are superficially similar to other non-engineered shallow wetlands, but ongoing use and maintenance might affect how BP contribute to aquatic biodiversity. We explored the 'within-habitat' effect of an ecosystem engineer by comparing active BP in southern Sweden with coexisting other wetlands (OW), using sedentary (plants) and mobile (water beetles) organisms as indicators. BP differed predictably from OW in environmental characteristics and were more heterogeneous. BP supported more plant species at plot (+15%) and site (+33%) scales, and plant beta diversity, based on turnover between plots, was 17% higher than in OW, contributing to a significantly larger species pool in BP (+17%). Beetles were not differentiated between BP and OW based on diversity measures but were 26% more abundant in BP. Independent of habitat creation beaver are thus significant agents of within-habitat heterogeneity that differentiates BP from other standing water habitat; as an integral component of the rewilding of wetlands re-establishing beaver should benefit aquatic biodiversity across multiple scales.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348870, year = {2018}, author = {Johnson, CN and Prior, LD and Archibald, S and Poulos, HM and Barton, AM and Williamson, GJ and Bowman, DMJS}, title = {Can trophic rewilding reduce the impact of fire in a more flammable world?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348870}, issn = {1471-2970}, abstract = {Large vertebrates affect fire regimes in several ways: by consuming plant matter that would otherwise accumulate as fuel; by controlling and varying the density of vegetation; and by engineering the soil and litter layer. These processes can regulate the frequency, intensity and extent of fire. The evidence for these effects is strongest in environments with intermediate rainfall, warm temperatures and graminoid-dominated ground vegetation. Probably, extinction of Quaternary megafauna triggered increased biomass burning in many such environments. Recent and continuing declines of large vertebrates are likely to be significant contributors to changes in fire regimes and vegetation that are currently being experienced in many parts of the world. To date, rewilding projects that aim to restore large herbivores have paid little attention to the value of large animals in moderating fire regimes. Rewilding potentially offers a powerful tool for managing the risks of wildfire and its impacts on natural and human values.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348869, year = {2018}, author = {Falcón, W and Hansen, DM}, title = {Island rewilding with giant tortoises in an era of climate change.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348869}, issn = {1471-2970}, abstract = {Replacing recently extinct endemic giant tortoises with extant, functional analogues provide the perhaps best examples of island rewilding to date. Yet, an efficient future application of this conservation action is challenging in an era of climate change. We here present and discuss a conceptual framework that can serve as a roadmap for the study and application of tortoise rewilding in an uncertain future. We focus on three main ecological functions mediated by giant tortoises, namely herbivory, seed dispersal and nutrient cycling, and discuss how climate change is likely to impact these. We then propose and discuss mitigation strategies such as artificial constructed shade sites and water holes that can help drive and maintain the ecosystem functions provided by the tortoises on a landscape scale. The application of the framework and the mitigation strategies are illustrated with examples from both wild and rewilded populations of the Aldabra giant tortoise, Aldabrachelys gigantea, in the Western Indian Ocean.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348868, year = {2018}, author = {van Klink, R and WallisDeVries, MF}, title = {Risks and opportunities of trophic rewilding for arthropod communities.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348868}, issn = {1471-2970}, abstract = {Trophic rewilding is a restoration strategy focusing on the restoration of trophic interactions to promote self-regulating, biodiverse ecosystems. It has been proposed as an alternative to traditional conservation management in abandoned or defaunated areas. Arthropods constitute the most species-rich group of eukaryotic organisms, but are rarely considered in rewilding. Here, we first present an overview of direct and indirect pathways by which large herbivores and predators affect arthropod communities. We then review the published evidence of the impacts of rewilding with large herbivores on arthropods, including grey literature. We find that systematic monitoring is rare and that a comparison with a relevant control treatment is usually lacking. Nevertheless, the available data suggest that when the important process of top-down control of large-herbivore populations is missing, arthropod diversity tends to decrease. To ensure that rewilding is supportive of biodiversity conservation, we propose that if natural processes can only partially be restored, substitutes for missing processes are applied. We also propose that boundaries of acceptable outcomes of rewilding actions should be defined a priori, particularly concerning biodiversity conservation, and that action is taken when these boundaries are transgressed. To evaluate the success of rewilding for biodiversity, monitoring of arthropod communities should be a key instrument.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348867, year = {2018}, author = {Cromsigt, JPGM and Te Beest, M and Kerley, GIH and Landman, M and le Roux, E and Smith, FA}, title = {Trophic rewilding as a climate change mitigation strategy?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348867}, issn = {1471-2970}, abstract = {The loss of megafauna at the terminal Pleistocene has been linked to a wide range of Earth-system-level changes, such as altered greenhouse gas budgets, fire regimes and biome-level vegetation changes. Given these influences and feedbacks, might part of the solution for mitigating anthropogenic climate change lie in the restoration of extant megafauna to ecosystems? Here, we explore the potential role of trophic rewilding on Earth's climate system. We first provide a novel synthesis of the various ways that megafauna interact with the major drivers of anthropogenic climate change, including greenhouse gas storage and emission, aerosols and albedo. We then explore the role of rewilding as a mitigation tool at two scales: (i) current and near-future opportunities for national or regional climate change mitigation portfolios, and (ii) more radical opportunities at the global scale. Finally, we identify major knowledge gaps that complicate the complete characterization of rewilding as a climate change mitigation strategy. Our perspective is urgent since we are losing the Earth's last remaining megafauna, and with it a potential option to address climate change.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348866, year = {2018}, author = {Bump, JK}, title = {Fertilizing riparian forests: nutrient repletion across ecotones with trophic rewilding.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348866}, issn = {1471-2970}, abstract = {Trophic rewilding maintains that large mammals are functionally important to resource subsidies and nutrient repletion, yet this prediction is understudied. Here, I report on the potential magnitude and variability of nitrogen that moose populations move from aquatic to terrestrial ecosystems. My aim is to provide justified approximations of the role of moose in the flux of a limiting nutrient across ecotones and to illustrate how this role is linked to wolf predation and climate warming. Using Isle Royale and northeastern Minnesota, USA as contrasting focal systems, I found that the long-term annual N gain for riparian forests likely ranges from 1 to 10 kg N ha-1 yr-1, depending on the heterogeneity of moose movements. For these systems, this range is equivalent to approximately 4-30% of net annual N mineralization, approximately 62-625% of annual N runoff, approximately 28-333% of annual atmospheric N deposition and approximately 31-312% of the N sequestered by trees. The N flux approximation is most sensitive to moose population levels and, as such, is influenced by wolves, climate warming and disease. The potential for other terrestrial ungulates that feed on aquatic plants to provide significant nutrient repletion across ecotones is unknown but important to examine in the context of trophic rewilding. The extent to which predators influence ungulate abundance indirectly impacts this nutrient repletion.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348865, year = {2018}, author = {Fuhlendorf, SD and Davis, CA and Elmore, RD and Goodman, LE and Hamilton, RG}, title = {Perspectives on grassland conservation efforts: should we rewild to the past or conserve for the future?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1761}, pages = {}, pmid = {30348865}, issn = {1471-2970}, abstract = {Grasslands are among the most imperilled biomes of the world. Identifying the most appropriate framework for restoring grasslands is dependent on the objectives of restoration, which is inherently determined by human priorities. Debates over the appropriate conservation model for grasslands have often focused on which species of herbivores should be the focus of restoration efforts. Here we discuss three perspectives of herbivore-based conservation in North American grasslands. First, the Pleistocene rewilding perspective is based upon the idea that early humans contributed to the demise of megafauna that were important to the evolution and development of many of North America's grasslands; therefore, their aim of restoration is rewilding of landscapes to pre-human times. Second, the bison rewilding perspective considers American bison a keystone herbivore that is culturally and ecologically important to North American grasslands. A third perspective focuses on restoring the pattern and processes of herbivory on grasslands and is less concerned about which herbivore is introduced to the landscape. We evaluate each of these three conservation perspectives in terms of a framework that includes a human domain, an herbivore domain and a biophysical domain. While all conservation perspectives partly address the three domains, they all fall short in key areas. Specifically, they fail to recognize that past, current and future humans are intimately linked to grassland patterns and processes and will continue to play a role in structuring grasslands. Furthermore, these perspectives seem to only superficially consider the role of fragmentation and climate change in influencing grassland patterns and processes. As such, we argue that future grassland conservation efforts must depend on the development of a model that better integrates societal, economic and policy objectives and recognizes climate change, fragmentation and humans as an integral part of these ecosystems.This article is part of the theme issue 'Trophic rewilding: consequences for ecosystems under global change'.}, } @article {pmid30348807, year = {2018}, author = {Meier, J and Zupan, A}, title = {Bridge trisections of knotted surfaces in 4-manifolds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10880-10886}, doi = {10.1073/pnas.1717171115}, pmid = {30348807}, issn = {1091-6490}, abstract = {We prove that every smoothly embedded surface in a 4-manifold can be isotoped to be in bridge position with respect to a given trisection of the ambient 4-manifold; that is, after isotopy, the surface meets components of the trisection in trivial disks or arcs. Such a decomposition, which we call a generalized bridge trisection, extends the authors' definition of bridge trisections for surfaces in [Formula: see text] Using this construction, we give diagrammatic representations called shadow diagrams for knotted surfaces in 4-manifolds. We also provide a low-complexity classification for these structures and describe several examples, including the important case of complex curves inside [Formula: see text] Using these examples, we prove that there exist exotic 4-manifolds with [Formula: see text]-trisections for certain values of g. We conclude by sketching a conjectural uniqueness result that would provide a complete diagrammatic calculus for studying knotted surfaces through their shadow diagrams.}, } @article {pmid30348806, year = {2018}, author = {Bisker, G and England, JL}, title = {Nonequilibrium associative retrieval of multiple stored self-assembly targets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10531-E10538}, pmid = {30348806}, issn = {1091-6490}, abstract = {Many biological systems rely on the ability to self-assemble different target structures using the same set of components. Equilibrium self-assembly suffers from a limited capacity in such cases, due to an increasing number of decoy states that grows rapidly with the number of targets encoded. Moreover, improving the kinetic stability of a target at equilibrium carries the price of introducing kinetic traps, leading to slower assembly. Using a toy physical model of interacting particles, we demonstrate that local driving can improve both the assembly time and kinetic stability of multitarget self-assembly, as well as reduce fluctuations around the target configuration. We further show that the local drive can result in a steady-state probability distribution over target structures that deviates from the Boltzmann distribution in a way that depends on the types of interactions that stabilize the targets. Our results illustrate the role that nonequilibrium driving plays in overcoming tradeoffs that are inherent to equilibrium assemblies.}, } @article {pmid30348805, year = {2018}, author = {Spering, M and Chow, HM}, title = {Rapid assessment of natural visual motion integration across primate species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11112-11114}, pmid = {30348805}, issn = {1091-6490}, mesh = {Animals ; *Callithrix ; Humans ; Longitudinal Studies ; *Macaca ; Motion ; Motion Perception ; Photic Stimulation ; Visual Cortex ; }, } @article {pmid30348804, year = {2018}, author = {Castro, NA and Gay, DT and Pinzón-Caicedo, J}, title = {Trisections of 4-manifolds with boundary.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10861-10868}, doi = {10.1073/pnas.1717170115}, pmid = {30348804}, issn = {1091-6490}, abstract = {Given a handle decomposition of a 4-manifold with boundary and an open book decomposition of the boundary, we show how to produce a trisection diagram of a trisection of the 4-manifold inducing the given open book. We do this by making the original proof of the existence of relative trisections more explicit in terms of handles. Furthermore, we extend this existence result to the case of 4-manifolds with multiple boundary components and show how trisected 4-manifolds with multiple boundary components glue together.}, } @article {pmid30348803, year = {2018}, author = {Feller, P and Klug, M and Schirmer, T and Zemke, D}, title = {Calculating the homology and intersection form of a 4-manifold from a trisection diagram.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10869-10874}, pmid = {30348803}, issn = {1091-6490}, abstract = {Given a diagram for a trisection of a 4-manifold X, we describe the homology and the intersection form of X in terms of the three subgroups of [Formula: see text] generated by the three sets of curves and the intersection pairing on [Formula: see text] This includes explicit formulas for the second and third homology groups of X as well an algorithm to compute the intersection form. Moreover, we show that all [Formula: see text]-trisections admit "algebraically trivial" diagrams.}, } @article {pmid30348802, year = {2018}, author = {Bethune, MT and Li, XH and Yu, J and McLaughlin, J and Cheng, D and Mathis, C and Moreno, BH and Woods, K and Knights, AJ and Garcia-Diaz, A and Wong, S and Hu-Lieskovan, S and Puig-Saus, C and Cebon, J and Ribas, A and Yang, L and Witte, ON and Baltimore, D}, title = {Isolation and characterization of NY-ESO-1-specific T cell receptors restricted on various MHC molecules.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10702-E10711}, pmid = {30348802}, issn = {1091-6490}, support = {P01 CA132681/CA/NCI NIH HHS/United States ; R35 CA197633/CA/NCI NIH HHS/United States ; }, abstract = {Tumor-specific T cell receptor (TCR) gene transfer enables specific and potent immune targeting of tumor antigens. Due to the prevalence of the HLA-A2 MHC class I supertype in most human populations, the majority of TCR gene therapy trials targeting public antigens have employed HLA-A2-restricted TCRs, limiting this approach to those patients expressing this allele. For these patients, TCR gene therapy trials have resulted in both tantalizing successes and lethal adverse events, underscoring the need for careful selection of antigenic targets. Broad and safe application of public antigen-targeted TCR gene therapies will require (i) selecting public antigens that are highly tumor-specific and (ii) targeting multiple epitopes derived from these antigens by obtaining an assortment of TCRs restricted by multiple common MHC alleles. The canonical cancer-testis antigen, NY-ESO-1, is not expressed in normal tissues but is aberrantly expressed across a broad array of cancer types. It has also been targeted with A2-restricted TCR gene therapy without adverse events or notable side effects. To enable the targeting of NY-ESO-1 in a broader array of HLA haplotypes, we isolated TCRs specific for NY-ESO-1 epitopes presented by four MHC molecules: HLA-A2, -B07, -B18, and -C03. Using these TCRs, we pilot an approach to extend TCR gene therapies targeting NY-ESO-1 to patient populations beyond those expressing HLA-A2.}, } @article {pmid30348801, year = {2018}, author = {Cáceres, R and Bojanala, N and Kelley, LC and Dreier, J and Manzi, J and Di Federico, F and Chi, Q and Risler, T and Testa, I and Sherwood, DR and Plastino, J}, title = {Forces drive basement membrane invasion in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11537-11542}, pmid = {30348801}, issn = {1091-6490}, support = {R01 GM079320/GM/NIGMS NIH HHS/United States ; R21 HD084290/HD/NICHD NIH HHS/United States ; R35 GM118049/GM/NIGMS NIH HHS/United States ; }, abstract = {During invasion, cells breach basement membrane (BM) barriers with actin-rich protrusions. It remains unclear, however, whether actin polymerization applies pushing forces to help break through BM, or whether actin filaments play a passive role as scaffolding for targeting invasive machinery. Here, using the developmental event of anchor cell (AC) invasion in Caenorhabditis elegans, we observe that the AC deforms the BM and underlying tissue just before invasion, exerting forces in the tens of nanonewtons range. Deformation is driven by actin polymerization nucleated by the Arp2/3 complex and its activators, whereas formins and cross-linkers are dispensable. Delays in invasion upon actin regulator loss are not caused by defects in AC polarity, trafficking, or secretion, as appropriate markers are correctly localized in the AC even when actin is reduced and invasion is disrupted. Overall force production emerges from this study as one of the main tools that invading cells use to promote BM disruption in C. elegans.}, } @article {pmid30348800, year = {2018}, author = {Bell, M and Hass, J and Rubinstein, JH and Tillmann, S}, title = {Computing trisections of 4-manifolds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10901-10907}, doi = {10.1073/pnas.1717173115}, pmid = {30348800}, issn = {1091-6490}, abstract = {We describe an algorithm to compute trisections of orientable four-manifolds using arbitrary triangulations as input. This results in explicit complexity bounds for the trisection genus of a 4-manifold in terms of the number of pentachora (4-simplices) in a triangulation.}, } @article {pmid30348799, year = {2018}, author = {Baykur, Rİ and Saeki, O}, title = {Simplified broken Lefschetz fibrations and trisections of 4-manifolds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10894-10900}, doi = {10.1073/pnas.1717175115}, pmid = {30348799}, issn = {1091-6490}, abstract = {Shapes of 4D spaces can be studied effectively via maps to standard surfaces. We explain, and illustrate by quintessential examples, how to simplify such generic maps on 4-manifolds topologically, to derive simple decompositions into much better-understood manifold pieces. Our methods not only allow us to produce various interesting families of examples but also to establish a correspondence between simplified broken Lefschetz fibrations and simplified trisections of closed, oriented 4-manifolds.}, } @article {pmid30348798, year = {2018}, author = {Garrigue, P and Tang, J and Ding, L and Bouhlel, A and Tintaru, A and Laurini, E and Huang, Y and Lyu, Z and Zhang, M and Fernandez, S and Balasse, L and Lan, W and Mas, E and Marson, D and Weng, Y and Liu, X and Giorgio, S and Iovanna, J and Pricl, S and Guillet, B and Peng, L}, title = {Self-assembling supramolecular dendrimer nanosystem for PET imaging of tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11454-11459}, pmid = {30348798}, issn = {1091-6490}, abstract = {Bioimaging plays an important role in cancer diagnosis and treatment. However, imaging sensitivity and specificity still constitute key challenges. Nanotechnology-based imaging is particularly promising for overcoming these limitations because nanosized imaging agents can specifically home in on tumors via the "enhanced permeation and retention" (EPR) effect, thus resulting in enhanced imaging sensitivity and specificity. Here, we report an original nanosystem for positron emission tomography (PET) imaging based on an amphiphilic dendrimer, which bears multiple PET reporting units at the terminals. This dendrimer is able to self-assemble into small and uniform nanomicelles, which accumulate in tumors for effective PET imaging. Benefiting from the combined dendrimeric multivalence and EPR-mediated passive tumor targeting, this nanosystem demonstrates superior imaging sensitivity and specificity, with up to 14-fold increased PET signal ratios compared with the clinical gold reference 2-fluorodeoxyglucose ([18F]FDG). Most importantly, this dendrimer system can detect imaging-refractory low-glucose-uptake tumors that are otherwise undetectable using [18F]FDG. In addition, it is endowed with an excellent safety profile and favorable pharmacokinetics for PET imaging. Consequently, this dendrimer nanosystem constitutes an effective and promising approach for cancer imaging. Our study also demonstrates that nanotechnology based on self-assembling dendrimers provides a fresh perspective for biomedical imaging and cancer diagnosis.}, } @article {pmid30348797, year = {2018}, author = {Aharonov, Y and Cohen, E and Tollaksen, J}, title = {Completely top-down hierarchical structure in quantum mechanics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11730-11735}, pmid = {30348797}, issn = {1091-6490}, abstract = {Can a large system be fully characterized using its subsystems via inductive reasoning? Is it possible to completely reduce the behavior of a complex system to the behavior of its simplest "atoms"? In this paper we answer these questions in the negative for a specific class of systems and measurements. After a general introduction of the topic, we present the main idea with a simple two-particle example, where strong correlations arise between two apparently empty boxes. This leads to surprising effects within atomic and electromagnetic systems. A general construction based on pre- and postselected ensembles is then suggested, wherein the N-body correlation can be genuinely perceived as a global property, as long as one is limited to performing measurements which we term "strictly local." We conclude that under certain boundary conditions, higher-order correlations within quantum mechanical systems can determine lower-order ones, but not vice versa. Surprisingly, the lower-order correlations provide no information whatsoever regarding the higher-order correlations. This supports a top-down structure in many-body quantum mechanics.}, } @article {pmid30348796, year = {2018}, author = {Meier, J and Zupan, A}, title = {Characterizing Dehn surgeries on links via trisections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10887-10893}, doi = {10.1073/pnas.1717187115}, pmid = {30348796}, issn = {1091-6490}, abstract = {We summarize and expand known connections between the study of Dehn surgery on links and the study of trisections of closed, smooth 4-manifolds. In particular, we propose a program in which trisections could be used to disprove the generalized property R conjecture, including a process that converts the potential counterexamples of Gompf, Scharlemann, and Thompson into genus four trisections of the standard 4-sphere that are unlikely to be standard. We also give an analog of the Casson-Gordon rectangle condition for trisections that obstructs reducibility of a given trisection.}, } @article {pmid30348795, year = {2018}, author = {Saintillan, D and Shelley, MJ and Zidovska, A}, title = {Extensile motor activity drives coherent motions in a model of interphase chromatin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11442-11447}, pmid = {30348795}, issn = {1091-6490}, support = {R00 GM104152/GM/NIGMS NIH HHS/United States ; }, abstract = {The 3D spatiotemporal organization of the human genome inside the cell nucleus remains a major open question in cellular biology. In the time between two cell divisions, chromatin-the functional form of DNA in cells-fills the nucleus in its uncondensed polymeric form. Recent in vivo imaging experiments reveal that the chromatin moves coherently, having displacements with long-ranged correlations on the scale of micrometers and lasting for seconds. To elucidate the mechanism(s) behind these motions, we develop a coarse-grained active polymer model where chromatin is represented as a confined flexible chain acted upon by molecular motors that drive fluid flows by exerting dipolar forces on the system. Numerical simulations of this model account for steric and hydrodynamic interactions as well as internal chain mechanics. These demonstrate that coherent motions emerge in systems involving extensile dipoles and are accompanied by large-scale chain reconfigurations and nematic ordering. Comparisons with experiments show good qualitative agreement and support the hypothesis that self-organizing long-ranged hydrodynamic couplings between chromatin-associated active motor proteins are responsible for the observed coherent dynamics.}, } @article {pmid30348794, year = {2018}, author = {Therkelsen, MD and Klose, T and Vago, F and Jiang, W and Rossmann, MG and Kuhn, RJ}, title = {Flaviviruses have imperfect icosahedral symmetry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11608-11612}, pmid = {30348794}, issn = {1091-6490}, support = {R01 AI073755/AI/NIAID NIH HHS/United States ; R01 AI076331/AI/NIAID NIH HHS/United States ; }, abstract = {Flaviviruses assemble initially in an immature, noninfectious state and undergo extensive conformational rearrangements to generate mature virus. Previous cryo-electron microscopy (cryo-EM) structural studies of flaviviruses assumed icosahedral symmetry and showed the concentric organization of the external glycoprotein shell, the lipid membrane, and the internal nucleocapsid core. We show here that when icosahedral symmetry constraints were excluded in calculating the cryo-EM reconstruction of an immature flavivirus, the nucleocapsid core was positioned asymmetrically with respect to the glycoprotein shell. The core was positioned closer to the lipid membrane at the proximal pole, and at the distal pole, the outer glycoprotein spikes and inner membrane leaflet were either perturbed or missing. In contrast, in the asymmetric reconstruction of a mature flavivirus, the core was positioned concentric with the glycoprotein shell. The deviations from icosahedral symmetry demonstrated that the core and glycoproteins have varied interactions, which likely promotes viral assembly and budding.}, } @article {pmid30348793, year = {2018}, author = {Kwon, MJ and Han, MH and Bagley, JA and Hyeon, DY and Ko, BS and Lee, YM and Cha, IJ and Kim, SY and Kim, DY and Kim, HM and Hwang, D and Lee, SB and Jan, YN}, title = {Coiled-coil structure-dependent interactions between polyQ proteins and Foxo lead to dendrite pathology and behavioral defects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10748-E10757}, pmid = {30348793}, issn = {1091-6490}, abstract = {Neurodegenerative disorders, such as Huntington's diseases and spinocerebellar ataxias (SCAs), are driven by proteins with expanded polyglutamine (polyQ) tracts. Recently, coiled-coil structures in polyQ regions of such proteins were shown to facilitate aggregate formation and ultimately lead to cell death. However, the molecular mechanism linking these structural domains to neuronal toxicity of polyQ proteins remains elusive. Here, we demonstrate that coiled-coil structures in the Q repeat region of SCA type 3 (SCA3) polyQ proteins confer protein toxicity in Drosophila neurons. To functionally characterize coiled-coil structures in the Q repeat regions, we generated three structural variants of SCA3 polyQ proteins: (i) MJDtr-76Q, containing both α-helical coiled-coil and β-sheet hairpin structures in the Q repeat region; (ii) MJDtr-70Q_cc0, possessing only α-helical coiled-coil structures due to the incorporation of β-sheet-breaking residues (Q-to-N or Q-to-E mutations); and (iii) MJDtr-70Q_pQp, with no secondary structure due to the introduced proline residues (Q-to-P mutations). Through comparative analysis of these variants, we found that coiled-coil structures facilitated nuclear localization of SCA3 polyQ proteins and induced dendrite defects in Drosophila dendritic arborization neurons. Furthermore, genetic and functional screening identified the transcription factor Foxo as a target of polyQ proteins, and coiled-coil-mediated interactions of Foxo and polyQ proteins in the nucleus resulted in the observed dendrite and behavioral defects in Drosophila These results demonstrate that coiled-coil structures of polyQ proteins are crucial for their neuronal toxicity, which is conferred through coiled-coil to coiled-coil interactions with the nuclear targets of these proteins.}, } @article {pmid30348792, year = {2018}, author = {Narango, DL and Tallamy, DW and Marra, PP}, title = {Nonnative plants reduce population growth of an insectivorous bird.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11549-11554}, pmid = {30348792}, issn = {1091-6490}, abstract = {Human-dominated landscapes represent one of the most rapidly expanding and least-understood ecosystems on earth. Yet, we know little about which features in these landscapes promote sustainable wildlife populations. Historically, in urban areas, landowners have converted native plant communities into habitats dominated by nonnative species that are not susceptible to pest damage and require little maintenance. However, nonnative plants are also poor at supporting insects that are critical food resources for higher order consumers. Despite the logical connection, no study has examined the impact of nonnative plants on subsequent population responses of vertebrate consumers. Here, we demonstrate that residential yards dominated by nonnative plants have lower arthropod abundance, forcing resident Carolina chickadees (Poecile carolinensis) to switch diets to less preferred prey and produce fewer young, or forgo reproduction in nonnative sites altogether. This leads to lower reproductive success and unsustainable population growth in these yards compared with those with >70% native plant biomass. Our results reveal that properties landscaped with nonnative plants function as population sinks for insectivorous birds. To promote sustainable food webs, urban planners and private landowners should prioritize native plant species.}, } @article {pmid30348791, year = {2018}, author = {Ahmed, F}, title = {QnAs with Helmut Schwarz.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11657-11658}, pmid = {30348791}, issn = {1091-6490}, } @article {pmid30348790, year = {2018}, author = {Krummel, MF and Mahale, JN and Uhl, LFK and Hardison, EA and Mujal, AM and Mazet, JM and Weber, RJ and Gartner, ZJ and Gérard, A}, title = {Paracrine costimulation of IFN-γ signaling by integrins modulates CD8 T cell differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11585-11590}, pmid = {30348790}, issn = {1091-6490}, support = {R01 AI052116/AI/NIAID NIH HHS/United States ; R01 AI114787/AI/NIAID NIH HHS/United States ; R03 AI119220/AI/NIAID NIH HHS/United States ; BB/R015651/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The cytokine IFN-γ is a critical regulator of immune system development and function. Almost all leukocytes express the receptor for IFN-γ, yet each cell type elicits a different response to this cytokine. Cell type-specific effects of IFN-γ make it difficult to predict the outcomes of the systemic IFN-γ blockade and limit its clinical application, despite many years of research. To better understand the cell-cell interactions and cofactors that specify IFN-γ functions, we focused on the function of IFN-γ on CD8 T cell differentiation. We demonstrated that during bacterial infection, IFN-γ is a dominant paracrine trigger that skews CD8 T cell differentiation toward memory. This skewing is preferentially driven by contact-dependent T cell-T cell (T-T) interactions and the localized IFN-γ secretion among activated CD8 T cells in a unique splenic microenvironment, and is less sensitive to concurrent IFN-γ production by other immune cell populations such as natural killer (NK) cells. Modulation of CD8 T cell differentiation by IFN-γ relies on a nonconventional IFN-γ outcome that occurs specifically within 24 hours following infection. This is driven by IFN-γ costimulation by integrins at T-T synapses, and leads to synergistic phosphorylation of the proximal STAT1 molecule and accelerated IL-2 receptor down-regulation. This study provides evidence of the importance of context-dependent cytokine signaling and gives another example of how cell clusters and the microenvironment drive unique biology.}, } @article {pmid30348789, year = {2018}, author = {Zichello, JM and Baab, KL and McNulty, KP and Raxworthy, CJ and Steiper, ME}, title = {Hominoid intraspecific cranial variation mirrors neutral genetic diversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11501-11506}, pmid = {30348789}, issn = {1091-6490}, abstract = {Natural selection, developmental constraint, and plasticity have all been invoked as explanations for intraspecific cranial variation in humans and apes. However, global patterns of human cranial variation are congruent with patterns of genetic variation, demonstrating that population history has influenced cranial variation in humans. Here we show that this finding is not unique to Homo sapiens but is also broadly evident across extant ape species. Specifically, taxa that exhibit greater intraspecific cranial shape variation also exhibit greater genetic diversity at neutral autosomal loci. Thus, cranial shape variation within hominoid taxa reflects the population history of each species. Our results suggest that neutral evolutionary processes such as mutation, gene flow, and genetic drift have played an important role in generating cranial variation within species. These findings are consistent with previous work on human cranial morphology and improve our understanding of the evolutionary processes that generate intraspecific cranial shape diversity within hominoids. This work has implications for the analysis of selective and developmental pressures on the cranium and for interpreting shape variation in fossil hominin crania.}, } @article {pmid30348788, year = {2018}, author = {}, title = {Correction to Supporting Information for Kwon et al., FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10515}, doi = {10.1073/pnas.1815642115}, pmid = {30348788}, issn = {1091-6490}, } @article {pmid30348787, year = {2018}, author = {Harcombe, WR and Chacón, JM and Adamowicz, EM and Chubiz, LM and Marx, CJ}, title = {Evolution of bidirectional costly mutualism from byproduct consumption.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {12000-12004}, pmid = {30348787}, issn = {1091-6490}, mesh = {Biological Evolution ; Carbon ; Escherichia coli/genetics/metabolism ; Evolution, Molecular ; Galactose/biosynthesis/metabolism ; Methionine/biosynthesis/genetics ; Microbial Interactions/*physiology ; Salmonella enterica/genetics/metabolism ; Symbiosis/*physiology ; }, abstract = {Mutualisms are essential for life, yet it is unclear how they arise. A two-stage process has been proposed for the evolution of mutualisms that involve exchanges of two costly resources. First, costly provisioning by one species may be selected for if that species gains a benefit from costless byproducts generated by a second species, and cooperators get disproportionate access to byproducts. Selection could then drive the second species to provide costly resources in return. Previously, a synthetic consortium evolved the first stage of this scenario: Salmonella enterica evolved costly production of methionine in exchange for costless carbon byproducts generated by an auxotrophic Escherichia coli Growth on agar plates localized the benefits of cooperation around methionine-secreting S. enterica Here, we report that further evolution of these partners on plates led to hypercooperative E. coli that secrete the sugar galactose. Sugar secretion arose repeatedly across replicate communities and is costly to E. coli producers, but enhances the growth of S. enterica The tradeoff between individual costs and group benefits led to maintenance of both cooperative and efficient E. coli genotypes in this spatially structured environment. This study provides an experimental example of de novo, bidirectional costly mutualism evolving from byproduct consumption. The results validate the plausibility of costly cooperation emerging from initially costless exchange, a scenario widely used to explain the origin of the mutualistic species interactions that are central to life on Earth.}, } @article {pmid30348786, year = {2018}, author = {Harder, N and Figueroa, L and Gillum, RM and Hangartner, D and Laitin, DD and Hainmueller, J}, title = {Multidimensional measure of immigrant integration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11483-11488}, pmid = {30348786}, issn = {1091-6490}, abstract = {The successful integration of immigrants into a host country's society, economy, and polity has become a major issue for policymakers in recent decades. Scientific progress in the study of immigrant integration has been hampered by the lack of a common measure of integration, which would allow for the accumulation of knowledge through comparison across studies, countries, and time. To address this fundamental problem, we propose the Immigration Policy Lab (IPL) Integration Index as a pragmatic and multidimensional measure of immigrant integration. The measure, both in the 12-item short form (IPL-12) and the 24-item long form (IPL-24), captures six dimensions of integration: psychological, economic, political, social, linguistic, and navigational. The measure can be used across countries, over time, and across different immigrant groups and can be administered through short questionnaires available in different modes. We report on four surveys we conducted to evaluate the empirical performance of our measure. The tests reveal that the measure distinguishes among immigrant groups with different expected levels of integration and also correlates with well-established predictors of integration.}, } @article {pmid30348785, year = {2018}, author = {Lindsey, PA and Miller, JRB and Petracca, LS and Coad, L and Dickman, AJ and Fitzgerald, KH and Flyman, MV and Funston, PJ and Henschel, P and Kasiki, S and Knights, K and Loveridge, AJ and Macdonald, DW and Mandisodza-Chikerema, RL and Nazerali, S and Plumptre, AJ and Stevens, R and Van Zyl, HW and Hunter, LTB}, title = {More than $1 billion needed annually to secure Africa's protected areas with lions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10788-E10796}, pmid = {30348785}, issn = {1091-6490}, abstract = {Protected areas (PAs) play an important role in conserving biodiversity and providing ecosystem services, yet their effectiveness is undermined by funding shortfalls. Using lions (Panthera leo) as a proxy for PA health, we assessed available funding relative to budget requirements for PAs in Africa's savannahs. We compiled a dataset of 2015 funding for 282 state-owned PAs with lions. We applied three methods to estimate the minimum funding required for effective conservation of lions, and calculated deficits. We estimated minimum required funding as $978/km2 per year based on the cost of effectively managing lions in nine reserves by the African Parks Network; $1,271/km2 based on modeled costs of managing lions at ≥50% carrying capacity across diverse conditions in 115 PAs; and $2,030/km2 based on Packer et al.'s [Packer et al. (2013) Ecol Lett 16:635-641] cost of managing lions in 22 unfenced PAs. PAs with lions require a total of $1.2 to $2.4 billion annually, or ∼$1,000 to 2,000/km2, yet received only $381 million annually, or a median of $200/km2 Ninety-six percent of range countries had funding deficits in at least one PA, with 88 to 94% of PAs with lions funded insufficiently. In funding-deficit PAs, available funding satisfied just 10 to 20% of PA requirements on average, and deficits total $0.9 to $2.1 billion. African governments and the international community need to increase the funding available for management by three to six times if PAs are to effectively conserve lions and other species and provide vital ecological and economic benefits to neighboring communities.}, } @article {pmid30348784, year = {2018}, author = {Wang, K and Holt, C and Lu, J and Brohus, M and Larsen, KT and Overgaard, MT and Wimmer, R and Van Petegem, F}, title = {Arrhythmia mutations in calmodulin cause conformational changes that affect interactions with the cardiac voltage-gated calcium channel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10556-E10565}, pmid = {30348784}, issn = {1091-6490}, support = {PJT-148632//Canadian Institutes of Health Research/International ; }, abstract = {Calmodulin (CaM) represents one of the most conserved proteins among eukaryotes and is known to bind and modulate more than a 100 targets. Recently, several disease-associated mutations have been identified in the CALM genes that are causative of severe cardiac arrhythmia syndromes. Although several mutations have been shown to affect the function of various cardiac ion channels, direct structural insights into any CaM disease mutation have been lacking. Here we report a crystallographic and NMR investigation of several disease mutant CaMs, linked to long-QT syndrome, in complex with the IQ domain of the cardiac voltage-gated calcium channel (CaV1.2). Surprisingly, two mutants (D95V, N97I) cause a major distortion of the C-terminal lobe, resulting in a pathological conformation not reported before. These structural changes result in altered interactions with the CaV1.2 IQ domain. Another mutation (N97S) reduces the affinity for Ca2+ by introducing strain in EF hand 3. A fourth mutant (F141L) shows structural changes in the Ca2+-free state that increase the affinity for the IQ domain. These results thus show that different mechanisms underlie the ability of CaM disease mutations to affect Ca2+-dependent inactivation of the voltage-gated calcium channel.}, } @article {pmid30348783, year = {2018}, author = {Young, LC and Hartig, N and Boned Del Río, I and Sari, S and Ringham-Terry, B and Wainwright, JR and Jones, GG and McCormick, F and Rodriguez-Viciana, P}, title = {SHOC2-MRAS-PP1 complex positively regulates RAF activity and contributes to Noonan syndrome pathogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10576-E10585}, pmid = {30348783}, issn = {1091-6490}, support = {R35 CA197709/CA/NCI NIH HHS/United States ; }, abstract = {Dephosphorylation of the inhibitory "S259" site on RAF kinases (S259 on CRAF, S365 on BRAF) plays a key role in RAF activation. The MRAS GTPase, a close relative of RAS oncoproteins, interacts with SHOC2 and protein phosphatase 1 (PP1) to form a heterotrimeric holoenzyme that dephosphorylates this S259 RAF site. MRAS and SHOC2 function as PP1 regulatory subunits providing the complex with striking specificity against RAF. MRAS also functions as a targeting subunit as membrane localization is required for efficient RAF dephosphorylation and ERK pathway regulation in cells. SHOC2's predicted structure shows remarkable similarities to the A subunit of PP2A, suggesting a case of convergent structural evolution with the PP2A heterotrimer. We have identified multiple regions in SHOC2 involved in complex formation as well as residues in MRAS switch I and the interswitch region that help account for MRAS's unique effector specificity for SHOC2-PP1. MRAS, SHOC2, and PPP1CB are mutated in Noonan syndrome, and we show that syndromic mutations invariably promote complex formation with each other, but not necessarily with other interactors. Thus, Noonan syndrome in individuals with SHOC2, MRAS, or PPPC1B mutations is likely driven at the biochemical level by enhanced ternary complex formation and highlights the crucial role of this phosphatase holoenzyme in RAF S259 dephosphorylation, ERK pathway dynamics, and normal human development.}, } @article {pmid30348782, year = {2018}, author = {Pifer, R and Russell, RM and Kumar, A and Curtis, MM and Sperandio, V}, title = {Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10712-E10719}, pmid = {30348782}, issn = {1091-6490}, support = {R01 AI114511/AI/NIAID NIH HHS/United States ; R01 AI077613/AI/NIAID NIH HHS/United States ; T32 AI007520/AI/NIAID NIH HHS/United States ; U01 AI077853/AI/NIAID NIH HHS/United States ; R01 AI053067/AI/NIAID NIH HHS/United States ; R37 AI053067/AI/NIAID NIH HHS/United States ; }, abstract = {The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagic Escherichia coli (EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection by Citrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.}, } @article {pmid30348781, year = {2018}, author = {VanderWaal, K and Deen, J}, title = {Global trends in infectious diseases of swine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11495-11500}, pmid = {30348781}, issn = {1091-6490}, abstract = {Pork accounts for more than one-third of meat produced worldwide and is an important component of global food security, agricultural economies, and trade. Infectious diseases are among the primary constraints to swine production, and the globalization of the swine industry has contributed to the emergence and spread of pathogens. Despite the importance of infectious diseases to animal health and the stability and productivity of the global swine industry, pathogens of swine have never been reviewed at a global scale. Here, we build a holistic global picture of research on swine pathogens to enhance preparedness and understand patterns of emergence and spread. By conducting a scoping review of more than 57,000 publications across 50 years, we identify priority pathogens globally and regionally, and characterize geographic and temporal trends in research priorities. Of the 40 identified pathogens, publication rates for eight pathogens increased faster than overall trends, suggesting that these pathogens may be emerging or constitute an increasing threat. We also compared regional patterns of pathogen prioritization in the context of policy differences, history of outbreaks, and differing swine health challenges faced in regions where swine production has become more industrialized. We documented a general increasing trend in importance of zoonotic pathogens and show that structural changes in the industry related to intensive swine production shift pathogen prioritization. Multinational collaboration networks were strongly shaped by region, colonial ties, and pig trade networks. This review represents the most comprehensive overview of research on swine infectious diseases to date.}, } @article {pmid30348780, year = {2018}, author = {Kirby, R and Thompson, A}, title = {A new invariant of 4-manifolds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10857-10860}, doi = {10.1073/pnas.1718953115}, pmid = {30348780}, issn = {1091-6490}, abstract = {We define an integer invariant [Formula: see text] of a smooth, compact, closed 4-manifold X by minimizing a certain complexity of a trisection of X over all trisections. The good feature of [Formula: see text] is that when [Formula: see text] and X is a homology 4-sphere, then X is diffeomorphic to the 4-sphere. Naturally, L is hard to compute.}, } @article {pmid30348779, year = {2018}, author = {Guo, JF and Zhang, L and Li, K and Mei, JP and Xue, J and Chen, J and Tang, X and Shen, L and Jiang, H and Chen, C and Guo, H and Wu, XL and Sun, SL and Xu, Q and Sun, QY and Chan, P and Shang, HF and Wang, T and Zhao, GH and Liu, JY and Xie, XF and Jiang, YQ and Liu, ZH and Zhao, YW and Zhu, ZB and Li, JD and Hu, ZM and Yan, XX and Fang, XD and Wang, GH and Zhang, FY and Xia, K and Liu, CY and Zhu, XW and Yue, ZY and Li, SC and Cai, HB and Zhang, ZH and Duan, RH and Tang, BS}, title = {Coding mutations in NUS1 contribute to Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11567-11572}, pmid = {30348779}, issn = {1091-6490}, abstract = {Whole-exome sequencing has been successful in identifying genetic factors contributing to familial or sporadic Parkinson's disease (PD). However, this approach has not been applied to explore the impact of de novo mutations on PD pathogenesis. Here, we sequenced the exomes of 39 early onset patients, their parents, and 20 unaffected siblings to investigate the effects of de novo mutations on PD. We identified 12 genes with de novo mutations (MAD1L1, NUP98, PPP2CB, PKMYT1, TRIM24, CEP131, CTTNBP2, NUS1, SMPD3, MGRN1, IFI35, and RUSC2), which could be functionally relevant to PD pathogenesis. Further analyses of two independent case-control cohorts (1,852 patients and 1,565 controls in one cohort and 3,237 patients and 2,858 controls in the other) revealed that NUS1 harbors significantly more rare nonsynonymous variants (P = 1.01E-5, odds ratio = 11.3) in PD patients than in controls. Functional studies in Drosophila demonstrated that the loss of NUS1 could reduce the climbing ability, dopamine level, and number of dopaminergic neurons in 30-day-old flies and could induce apoptosis in fly brain. Together, our data suggest that de novo mutations could contribute to early onset PD pathogenesis and identify NUS1 as a candidate gene for PD.}, } @article {pmid30348778, year = {2018}, author = {Foteinou, PT and Venkataraman, A and Francey, LJ and Anafi, RC and Hogenesch, JB and Doyle, FJ}, title = {Computational and experimental insights into the circadian effects of SIRT1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11643-11648}, pmid = {30348778}, issn = {1091-6490}, support = {R01 NS054794/NS/NINDS NIH HHS/United States ; }, abstract = {The circadian clock orchestrates 24-h rhythms in physiology in most living organisms. At the molecular level, the dogma is that circadian oscillations are based on a negative transcriptional feedback loop. Recent studies found the NAD+-dependent histone deacetylase, SIRT1, directly regulates acetylation status of clock components and influences circadian amplitude in cells. While Nakahata et al. [Nakahata Y, Kaluzova M (2008) Cell 134:329-340] reported that loss of SIRT1 increases amplitude through BMAL1 acetylation, Asher et al. [Asher G, Gatfield D (2008) Cell 134:317-328] reported that loss of SIRT1 decreases amplitude through an increase in acetylated PER2. To address this SIRT1 paradox, we developed a circadian enzymatic model. Predictions from this model and experimental validation strongly align with the findings of Asher et al., with PER2 as the primary target of SIRT1. Further, the model suggested SIRT1 influences BMAL1 expression through actions on PGC1α. We validated this finding experimentally. Thus, our computational and experimental approaches suggest SIRT1 positively regulates clock function through actions on PER2 and PGC1α.}, } @article {pmid30348777, year = {2018}, author = {}, title = {Correction for Su et al., Pyruvate cycle increases aminoglycoside efficacy and provides respiratory energy in bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1816299115}, pmid = {30348777}, issn = {1091-6490}, } @article {pmid30348776, year = {2018}, author = {Klug, M}, title = {Functoriality of group trisections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10875-10879}, doi = {10.1073/pnas.1717167115}, pmid = {30348776}, issn = {1091-6490}, abstract = {Building on work by Stallings, Jaco, and Hempel in three dimensions and a more recent four-dimensional analog by Abrams, Kirby, and Gay, we show how the splitting homomorphism and group trisection constructions can be extended to functors between appropriate categories. This further enhances the bridge between smooth four-dimensional topology and the group theory of free and surface groups.}, } @article {pmid30348775, year = {2018}, author = {Guo, Q and Yoshida, Y and Major, IT and Wang, K and Sugimoto, K and Kapali, G and Havko, NE and Benning, C and Howe, GA}, title = {JAZ repressors of metabolic defense promote growth and reproductive fitness in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10768-E10777}, pmid = {30348775}, issn = {1091-6490}, support = {R01 GM057795/GM/NIGMS NIH HHS/United States ; }, abstract = {Plant immune responses mediated by the hormone jasmonoyl-l-isoleucine (JA-Ile) are metabolically costly and often linked to reduced growth. Although it is known that JA-Ile activates defense responses by triggering the degradation of JASMONATE ZIM DOMAIN (JAZ) transcriptional repressor proteins, expansion of the JAZ gene family in vascular plants has hampered efforts to understand how this hormone impacts growth and other physiological tasks over the course of ontogeny. Here, we combined mutations within the 13-member Arabidopsis JAZ gene family to investigate the effects of chronic JAZ deficiency on growth, defense, and reproductive output. A higher-order mutant (jaz decuple, jazD) defective in 10 JAZ genes (JAZ1-7, -9, -10, and -13) exhibited robust resistance to insect herbivores and fungal pathogens, which was accompanied by slow vegetative growth and poor reproductive performance. Metabolic phenotypes of jazD discerned from global transcript and protein profiling were indicative of elevated carbon partitioning to amino acid-, protein-, and endoplasmic reticulum body-based defenses controlled by the JA-Ile and ethylene branches of immunity. Resource allocation to a strong defense sink in jazD leaves was associated with increased respiration and hallmarks of carbon starvation but no overt changes in photosynthetic rate. Depletion of the remaining JAZ repressors in jazD further exaggerated growth stunting, nearly abolished seed production and, under extreme conditions, caused spreading necrotic lesions and tissue death. Our results demonstrate that JAZ proteins promote growth and reproductive success at least in part by preventing catastrophic metabolic effects of an unrestrained immune response.}, } @article {pmid30348774, year = {2018}, author = {Altman, J and Ukhvatkina, ON and Omelko, AM and Macek, M and Plener, T and Pejcha, V and Cerny, T and Petrik, P and Srutek, M and Song, JS and Zhmerenetsky, AA and Vozmishcheva, AS and Krestov, PV and Petrenko, TY and Treydte, K and Dolezal, J}, title = {Poleward migration of the destructive effects of tropical cyclones during the 20th century.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11543-11548}, pmid = {30348774}, issn = {1091-6490}, abstract = {Determination of long-term tropical cyclone (TC) variability is of enormous importance to society; however, changes in TC activity are poorly understood owing to discrepancies among various datasets and limited span of instrumental records. While the increasing intensity and frequency of TCs have been previously documented on a long-term scale using various proxy records, determination of their poleward migration has been based mostly on short-term instrumental data. Here we present a unique tree-ring-based approach for determination of long-term variability in TC activity via forest disturbance rates in northeast Asia (33-45°N). Our results indicate significant long-term changes in TC activity, with increased rates of disturbances in the northern latitudes over the past century. The disturbance frequency was stable over time in the southern latitudes, however. Our findings of increasing disturbance frequency in the areas formerly situated at the edge of TC activity provide evidence supporting the broad relevance of poleward migration of TCs. Our results significantly enhance our understanding of the effects of climate change on TCs and emphasize the need for determination of long-term variation of past TC activity to improve future TC projections.}, } @article {pmid30348773, year = {2018}, author = {Parent, LR and Onofrei, D and Xu, D and Stengel, D and Roehling, JD and Addison, JB and Forman, C and Amin, SA and Cherry, BR and Yarger, JL and Gianneschi, NC and Holland, GP}, title = {Hierarchical spidroin micellar nanoparticles as the fundamental precursors of spider silks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11507-11512}, pmid = {30348773}, issn = {1091-6490}, support = {F32 EB021859/EB/NIBIB NIH HHS/United States ; }, abstract = {Many natural silks produced by spiders and insects are unique materials in their exceptional toughness and tensile strength, while being lightweight and biodegradable-properties that are currently unparalleled in synthetic materials. Myriad approaches have been attempted to prepare artificial silks from recombinant spider silk spidroins but have each failed to achieve the advantageous properties of the natural material. This is because of an incomplete understanding of the in vivo spidroin-to-fiber spinning process and, particularly, because of a lack of knowledge of the true morphological nature of spidroin nanostructures in the precursor dope solution and the mechanisms by which these nanostructures transform into micrometer-scale silk fibers. Herein we determine the physical form of the natural spidroin precursor nanostructures stored within spider glands that seed the formation of their silks and reveal the fundamental structural transformations that occur during the initial stages of extrusion en route to fiber formation. Using a combination of solution phase diffusion NMR and cryogenic transmission electron microscopy (cryo-TEM), we reveal direct evidence that the concentrated spidroin proteins are stored in the silk glands of black widow spiders as complex, hierarchical nanoassemblies (∼300 nm diameter) that are composed of micellar subdomains, substructures that themselves are engaged in the initial nanoscale transformations that occur in response to shear. We find that the established micelle theory of silk fiber precursor storage is incomplete and that the first steps toward liquid crystalline organization during silk spinning involve the fibrillization of nanoscale hierarchical micelle subdomains.}, } @article {pmid30348772, year = {2018}, author = {Chen, YH and Lee, HJ and Lee, MT and Wu, YT and Lee, YH and Hwang, LL and Hung, MS and Zimmer, A and Mackie, K and Chiou, LC}, title = {Median nerve stimulation induces analgesia via orexin-initiated endocannabinoid disinhibition in the periaqueductal gray.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10720-E10729}, pmid = {30348772}, issn = {1091-6490}, support = {K05 DA021696/DA/NIDA NIH HHS/United States ; R01 DA011322/DA/NIDA NIH HHS/United States ; }, abstract = {Adequate pain management remains an unmet medical need. We previously revealed an opioid-independent analgesic mechanism mediated by orexin 1 receptor (OX1R)-initiated 2-arachidonoylglycerol (2-AG) signaling in the ventrolateral periaqueductal gray (vlPAG). Here, we found that low-frequency median nerve stimulation (MNS) through acupuncture needles at the PC6 (Neiguan) acupoint (MNS-PC6) induced an antinociceptive effect that engaged this mechanism. In mice, MNS-PC6 reduced acute thermal nociceptive responses and neuropathy-induced mechanical allodynia, increased the number of c-Fos-immunoreactive hypothalamic orexin neurons, and led to higher orexin A and lower GABA levels in the vlPAG. Such responses were not seen in mice with PC6 needle insertion only or electrical stimulation of the lateral deltoid, a nonmedian nerve-innervated location. Directly stimulating the surgically exposed median nerve also increased vlPAG orexin A levels. MNS-PC6-induced antinociception (MNS-PC6-IA) was prevented by proximal block of the median nerve with lidocaine as well as by systemic or intravlPAG injection of an antagonist of OX1Rs or cannabinoid 1 receptors (CB1Rs) but not by opioid receptor antagonists. Systemic blockade of OX1Rs or CB1Rs also restored vlPAG GABA levels after MNS-PC6. A cannabinoid (2-AG)-dependent mechanism was also implicated by the observations that MNS-PC6-IA was prevented by intravlPAG inhibition of 2-AG synthesis and was attenuated in Cnr1-/- mice. These findings suggest that PC6-targeting low-frequency MNS activates hypothalamic orexin neurons, releasing orexins to induce analgesia through a CB1R-dependent cascade mediated by OX1R-initiated 2-AG retrograde disinhibition in the vlPAG. The opioid-independent characteristic of MNS-PC6-induced analgesia may provide a strategy for pain management in opioid-tolerant patients.}, } @article {pmid30348771, year = {2018}, author = {Lindsey, R and Daluiski, A and Chopra, S and Lachapelle, A and Mozer, M and Sicular, S and Hanel, D and Gardner, M and Gupta, A and Hotchkiss, R and Potter, H}, title = {Deep neural network improves fracture detection by clinicians.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11591-11596}, pmid = {30348771}, issn = {1091-6490}, abstract = {Suspected fractures are among the most common reasons for patients to visit emergency departments (EDs), and X-ray imaging is the primary diagnostic tool used by clinicians to assess patients for fractures. Missing a fracture in a radiograph often has severe consequences for patients, resulting in delayed treatment and poor recovery of function. Nevertheless, radiographs in emergency settings are often read out of necessity by emergency medicine clinicians who lack subspecialized expertise in orthopedics, and misdiagnosed fractures account for upward of four of every five reported diagnostic errors in certain EDs. In this work, we developed a deep neural network to detect and localize fractures in radiographs. We trained it to accurately emulate the expertise of 18 senior subspecialized orthopedic surgeons by having them annotate 135,409 radiographs. We then ran a controlled experiment with emergency medicine clinicians to evaluate their ability to detect fractures in wrist radiographs with and without the assistance of the deep learning model. The average clinician's sensitivity was 80.8% (95% CI, 76.7-84.1%) unaided and 91.5% (95% CI, 89.3-92.9%) aided, and specificity was 87.5% (95 CI, 85.3-89.5%) unaided and 93.9% (95% CI, 92.9-94.9%) aided. The average clinician experienced a relative reduction in misinterpretation rate of 47.0% (95% CI, 37.4-53.9%). The significant improvements in diagnostic accuracy that we observed in this study show that deep learning methods are a mechanism by which senior medical specialists can deliver their expertise to generalists on the front lines of medicine, thereby providing substantial improvements to patient care.}, } @article {pmid30348770, year = {2018}, author = {Uhl, GR and Martinez, MJ and Paik, P and Sulima, A and Bi, GH and Iyer, MR and Gardner, E and Rice, KC and Xi, ZX}, title = {Cocaine reward is reduced by decreased expression of receptor-type protein tyrosine phosphatase D (PTPRD) and by a novel PTPRD antagonist.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11597-11602}, pmid = {30348770}, issn = {1091-6490}, abstract = {Receptor-type protein tyrosine phosphatase D (PTPRD) is a neuronal cell-adhesion molecule/synaptic specifier that has been implicated in addiction vulnerability and stimulant reward by human genomewide association and mouse cocaine-conditioned place-preference data. However, there have been no reports of effects of reduced expression on cocaine self-administration. There have been no reports of PTPRD targeting by any small molecule. There are no data about behavioral effects of any PTPRD ligand. We now report (i) robust effects of heterozygous PTPRD KO on cocaine self-administration (These data substantially extend prior conditioned place-preference data and add to the rationale for PTPRD as a target for addiction therapeutics.); (ii) identification of 7-butoxy illudalic acid analog (7-BIA) as a small molecule that targets PTPRD and inhibits its phosphatase with some specificity; (iii) lack of toxicity when 7-BIA is administered to mice acutely or with repeated dosing; (iv) reduced cocaine-conditioned place preference when 7-BIA is administered before conditioning sessions; and (v) reductions in well-established cocaine self-administration when 7-BIA is administered before a session (in WT, not PTPRD heterozygous KOs). These results add to support for PTPRD as a target for medications to combat cocaine use disorders. 7-BIA provides a lead compound for addiction therapeutics.}, } @article {pmid30348769, year = {2018}, author = {Zhou, W and Cheung, K and Kyu, S and Wang, L and Guan, Z and Kurien, PA and Bickler, PE and Jan, LY}, title = {Activation of orexin system facilitates anesthesia emergence and pain control.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10740-E10747}, pmid = {30348769}, issn = {1091-6490}, support = {R01 NS069229/NS/NINDS NIH HHS/United States ; R01 NS100801/NS/NINDS NIH HHS/United States ; }, abstract = {Orexin (also known as hypocretin) neurons in the hypothalamus play an essential role in sleep-wake control, feeding, reward, and energy homeostasis. The likelihood of anesthesia and sleep sharing common pathways notwithstanding, it is important to understand the processes underlying emergence from anesthesia. In this study, we investigated the role of the orexin system in anesthesia emergence, by specifically activating orexin neurons utilizing the designer receptors exclusively activated by designer drugs (DREADD) chemogenetic approach. With injection of adeno-associated virus into the orexin-Cre transgenic mouse brain, we expressed the DREADD receptor hM3Dq specifically in orexin neurons and applied the hM3Dq ligand clozapine to activate orexin neurons. We monitored orexin neuronal activities by c-Fos staining and whole-cell patch-clamp recording and examined the consequence of orexin neuronal activation via EEG recording. Our results revealed that the orexin-DREADD mice with activated orexin neurons emerged from anesthesia with significantly shorter latency than the control mice. As an indication of reduced pain sensitivity, these orexin-DREADD mice took longer to respond to the 55 °C thermal stimuli in the hot plate test and exhibited significantly less frequent licking of the formalin-injected paw in the formalin test. Our study suggests that approaches to activate the orexin system can be beneficial in postoperative recovery.}, } @article {pmid30348768, year = {2018}, author = {Wang, X and O'Connor, JK and Maina, JN and Pan, Y and Wang, M and Wang, Y and Zheng, X and Zhou, Z}, title = {Archaeorhynchus preserving significant soft tissue including probable fossilized lungs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11555-11560}, pmid = {30348768}, issn = {1091-6490}, abstract = {We describe a specimen of the basal ornithuromorph Archaeorhynchus spathula from the Lower Cretaceous Jiufotang Formation with extensive soft tissue preservation. Although it is the fifth specimen to be described, unlike the others it preserves significant traces of the plumage, revealing a pintail morphology previously unrecognized among Mesozoic birds, but common in extant neornithines. In addition, this specimen preserves the probable remnants of the paired lungs, an identification supported by topographical and macro- and microscopic anatomical observations. The preserved morphology reveals a lung very similar to that of living birds. It indicates that pulmonary specializations such as exceedingly subdivided parenchyma that allow birds to achieve the oxygen acquisition capacity necessary to support powered flight were present in ornithuromorph birds 120 Mya. Among extant air breathing vertebrates, birds have structurally the most complex and functionally the most efficient respiratory system, which facilitates their highly energetically demanding form of locomotion, even in extremely oxygen-poor environments. Archaeorhynchus is commonly resolved as the most basal known ornithuromorph bird, capturing a stage of avian evolution in which skeletal indicators of respiration remain primitive yet the lung microstructure appears modern. This adds to growing evidence that many physiological modifications of soft tissue systems (e.g., digestive system and respiratory system) that characterize living birds and are key to their current success may have preceded the evolution of obvious skeletal adaptations traditionally tracked through the fossil record.}, } @article {pmid30348767, year = {2018}, author = {Roa, J and Barroso, A and Ruiz-Pino, F and Vázquez, MJ and Seoane-Collazo, P and Martínez-Sanchez, N and García-Galiano, D and Ilhan, T and Pineda, R and León, S and Manfredi-Lozano, M and Heras, V and Poutanen, M and Castellano, JM and Gaytan, F and Diéguez, C and Pinilla, L and López, M and Tena-Sempere, M}, title = {Metabolic regulation of female puberty via hypothalamic AMPK-kisspeptin signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10758-E10767}, pmid = {30348767}, issn = {1091-6490}, abstract = {Conditions of metabolic distress, from malnutrition to obesity, impact, via as yet ill-defined mechanisms, the timing of puberty, whose alterations can hamper later cardiometabolic health and even life expectancy. AMP-activated protein kinase (AMPK), the master cellular energy sensor activated in conditions of energy insufficiency, has a major central role in whole-body energy homeostasis. However, whether brain AMPK metabolically modulates puberty onset remains unknown. We report here that central AMPK interplays with the puberty-activating gene, Kiss1, to control puberty onset. Pubertal subnutrition, which delayed puberty, enhanced hypothalamic pAMPK levels, while activation of brain AMPK in immature female rats substantially deferred puberty. Virogenetic overexpression of a constitutively active form of AMPK, selectively in the hypothalamic arcuate nucleus (ARC), which holds a key population of Kiss1 neurons, partially delayed puberty onset and reduced luteinizing hormone levels. ARC Kiss1 neurons were found to express pAMPK, and activation of AMPK reduced ARC Kiss1 expression. The physiological relevance of this pathway was attested by conditional ablation of the AMPKα1 subunit in Kiss1 cells, which largely prevented the delay in puberty onset caused by chronic subnutrition. Our data demonstrate that hypothalamic AMPK signaling plays a key role in the metabolic control of puberty, acting via a repressive modulation of ARC Kiss1 neurons in conditions of negative energy balance.}, } @article {pmid30348766, year = {2018}, author = {Scoccimarro, E and Bellucci, A and Storto, A and Gualdi, S and Masina, S and Navarra, A}, title = {Remote subsurface ocean temperature as a predictor of Atlantic hurricane activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11460-11464}, pmid = {30348766}, issn = {1091-6490}, abstract = {Predicting North Atlantic hurricane activity months in advance is of great potential societal significance. The ocean temperature, both in terms of North Atlantic/tropical averages and upper ocean heat content, is demonstrated to be a significant predictor. To investigate the relationship between the thermal state of the Atlantic Ocean and the tropical cyclone (TC) activity in terms of accumulated cyclone energy (ACE), we use observed 1980-2015 TC records and a 1/4° resolution global ocean reanalysis. This paper highlights the nonlocal effect associated with eastern Atlantic Ocean temperature, via a reduction of wind shear, and provides additional predictive skill of TC activity, when considering subsurface temperature instead of sea surface temperature (SST) only. The most active TC seasons occur for lower than normal wind shear conditions over the main development region, which is also driven by reduced trade wind strength. A significant step toward operationally reliable TC activity predictions is gained after including upper ocean mean temperatures over the eastern Atlantic domain. Remote effects are found to provide potential skill of ACE up to 3 months in advance. These results indicate that consideration of the upper 40-m ocean average temperature improves upon a prediction of September Atlantic hurricane activity using only SST.}, } @article {pmid30348765, year = {2018}, author = {Shin, W and Kim, HJ}, title = {Intestinal barrier dysfunction orchestrates the onset of inflammatory host-microbiome cross-talk in a human gut inflammation-on-a-chip.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10539-E10547}, pmid = {30348765}, issn = {1091-6490}, abstract = {The initiation of intestinal inflammation involves complex intercellular cross-talk of inflammatory cells, including the epithelial and immune cells, and the gut microbiome. This multicellular complexity has hampered the identification of the trigger that orchestrates the onset of intestinal inflammation. To identify the initiator of inflammatory host-microbiome cross-talk, we leveraged a pathomimetic "gut inflammation-on-a-chip" undergoing physiological flow and motions that recapitulates the pathophysiology of dextran sodium sulfate (DSS)-induced inflammation in murine models. DSS treatment significantly impaired, without cytotoxic damage, epithelial barrier integrity, villous microarchitecture, and mucus production, which were rapidly recovered after cessation of DSS treatment. We found that the direct contact of DSS-sensitized epithelium and immune cells elevates oxidative stress, in which the luminal microbial stimulation elicited the production of inflammatory cytokines and immune cell recruitment. In contrast, an intact intestinal barrier successfully suppressed oxidative stress and inflammatory cytokine production against the physiological level of lipopolysaccharide or nonpathogenic Escherichia coli in the presence of immune elements. Probiotic treatment effectively reduced the oxidative stress, but it failed to ameliorate the epithelial barrier dysfunction and proinflammatory response when the probiotic administration happened after the DSS-induced barrier disruption. Maintenance of epithelial barrier function was necessary and sufficient to control the physiological oxidative stress and proinflammatory cascades, suggesting that "good fences make good neighbors." Thus, the modular gut inflammation-on-a-chip identifies the mechanistic contribution of barrier dysfunction mediated by intercellular host-microbiome cross-talk to the onset of intestinal inflammation.}, } @article {pmid30348764, year = {2018}, author = {Kirby, R}, title = {Trisections of 4-manifolds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10853-10856}, pmid = {30348764}, issn = {1091-6490}, } @article {pmid30348763, year = {2018}, author = {Powell, CJ and Ramaswamy, R and Kelsen, A and Hamelin, DJ and Warshaw, DM and Bosch, J and Burke, JE and Ward, GE and Boulanger, MJ}, title = {Structural and mechanistic insights into the function of the unconventional class XIV myosin MyoA from Toxoplasma gondii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10548-E10555}, pmid = {30348763}, issn = {1091-6490}, support = {P01 HL128192/HL/NHLBI NIH HHS/United States ; R01 AI054961/AI/NIAID NIH HHS/United States ; R01 GM094229/GM/NIGMS NIH HHS/United States ; R56 AI054961/AI/NIAID NIH HHS/United States ; 148596//Canadian Institutes of Health Research/International ; }, abstract = {Parasites of the phylum Apicomplexa are responsible for significant morbidity and mortality on a global scale. Central to the virulence of these pathogens are the phylum-specific, unconventional class XIV myosins that power the essential processes of parasite motility and host cell invasion. Notably, class XIV myosins differ from human myosins in key functional regions, yet they are capable of fast movement along actin filaments with kinetics rivaling previously studied myosins. Toward establishing a detailed molecular mechanism of class XIV motility, we determined the 2.6-Å resolution crystal structure of the Toxoplasma gondii MyoA (TgMyoA) motor domain. Structural analysis reveals intriguing strategies for force transduction and chemomechanical coupling that rely on a divergent SH1/SH2 region, the class-defining "HYAG"-site polymorphism, and the actin-binding surface. In vitro motility assays and hydrogen-deuterium exchange coupled with MS further reveal the mechanistic underpinnings of phosphorylation-dependent modulation of TgMyoA motility whereby localized regions of increased stability and order correlate with enhanced motility. Analysis of solvent-accessible pockets reveals striking differences between apicomplexan class XIV and human myosins. Extending these analyses to high-confidence homology models of Plasmodium and Cryptosporidium MyoA motor domains supports the intriguing potential of designing class-specific, yet broadly active, apicomplexan myosin inhibitors. The successful expression of the functional TgMyoA complex combined with our crystal structure of the motor domain provides a strong foundation in support of detailed structure-function studies and enables the development of small-molecule inhibitors targeting these devastating global pathogens.}, } @article {pmid30348762, year = {2018}, author = {Kim, B and Yoon, S and Nakajima, R and Lee, HJ and Lim, HJ and Lee, YK and Choi, JS and Yoon, BJ and Augustine, GJ and Baik, JH}, title = {Dopamine D2 receptor-mediated circuit from the central amygdala to the bed nucleus of the stria terminalis regulates impulsive behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10730-E10739}, pmid = {30348762}, issn = {1091-6490}, abstract = {Impulsivity is closely associated with addictive disorders, and changes in the brain dopamine system have been proposed to affect impulse control in reward-related behaviors. However, the central neural pathways through which the dopamine system controls impulsive behavior are still unclear. We found that the absence of the D2 dopamine receptor (D2R) increased impulsive behavior in mice, whereas restoration of D2R expression specifically in the central amygdala (CeA) of D2R knockout mice (Drd2-/-) normalized their enhanced impulsivity. Inhibitory synaptic output from D2R-expressing neurons in the CeA underlies modulation of impulsive behavior because optogenetic activation of D2R-positive inhibitory neurons that project from the CeA to the bed nucleus of the stria terminalis (BNST) attenuate such behavior. Our identification of the key contribution of D2R-expressing neurons in the CeA → BNST circuit to the control of impulsive behavior reveals a pathway that could serve as a target for approaches to the management of neuropsychiatric disorders associated with impulsivity.}, } @article {pmid30348761, year = {2018}, author = {Rubinstein, JH and Tillmann, S}, title = {Generalized trisections in all dimensions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10908-10913}, doi = {10.1073/pnas.1718961115}, pmid = {30348761}, issn = {1091-6490}, abstract = {This paper describes a generalization of Heegaard splittings of 3-manifolds and trisections of 4-manifolds to all dimensions, using triangulations as a key tool. In particular, every closed piecewise linear n-manifold can be divided into [Formula: see text] n-dimensional 1-handlebodies, where [Formula: see text] or [Formula: see text], such that intersections of the handlebodies have spines of small dimensions. Several applications, constructions, and generalizations of our approach are given.}, } @article {pmid30348760, year = {2018}, author = {Hrycaj, SM and Marty-Santos, L and Cebrian, C and Rasky, AJ and Ptaschinski, C and Lukacs, NW and Wellik, DM}, title = {Hox5 genes direct elastin network formation during alveologenesis by regulating myofibroblast adhesion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10605-E10614}, pmid = {30348760}, issn = {1091-6490}, support = {P30 CA046592/CA/NCI NIH HHS/United States ; R01 HL119215/HL/NHLBI NIH HHS/United States ; T32 HL007749/HL/NHLBI NIH HHS/United States ; UL1 TR002240/TR/NCATS NIH HHS/United States ; }, abstract = {Hox5 genes (Hoxa5, Hoxb5, Hoxc5) are exclusively expressed in the lung mesenchyme during embryogenesis, and the most severe phenotypes result from constitutive loss of function of all three genes. Because Hox5 triple null mutants exhibit perinatal lethality, the contribution of this paralogous group to postembryonic lung development is unknown. Intriguingly, expression of all three Hox5 genes peaks during the first 2 weeks after birth, reaching levels far exceeding those measured at embryonic stages, and surviving Hoxa5 single and Hox5 AabbCc compound mutants exhibit defects in the localization of alveolar myofibroblasts. To define the contribution of the entire Hox5 paralogous group to this process, we generated an Hoxa5 conditional allele to use with our existing null alleles for Hoxb5 and Hoxc5 Postnatally, mesenchymal deletion of Hoxa5 in an Hoxb5/Hoxc5 double-mutant background results in severe alveolar simplification. The elastin network required for alveolar formation is dramatically disrupted in Hox5 triple mutants, while the basal lamina, interstitial matrix, and fibronectin are normal. Alveolar myofibroblasts remain Pdgfrα+/SMA+ double positive and present in normal numbers, indicating that the irregular elastin network is not due to fibroblast differentiation defects. Rather, we observe that SMA+ myofibroblasts of Hox5 triple mutants are morphologically abnormal both in vivo and in vitro with highly reduced adherence to fibronectin. This loss of adhesion is a result of loss of the integrin heterodimer Itga5b1 in mutant fibroblasts. Collectively, these data show an important role for Hox5 genes in lung fibroblast adhesion necessary for proper elastin network formation during alveologenesis.}, } @article {pmid30348759, year = {2018}, author = {Magnuson, AM and Kiner, E and Ergun, A and Park, JS and Asinovski, N and Ortiz-Lopez, A and Kilcoyne, A and Paoluzzi-Tomada, E and Weissleder, R and Mathis, D and Benoist, C}, title = {Identification and validation of a tumor-infiltrating Treg transcriptional signature conserved across species and tumor types.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10672-E10681}, pmid = {30348759}, issn = {1091-6490}, support = {T32 CA079443/CA/NCI NIH HHS/United States ; }, abstract = {FoxP3+ T regulatory (Treg) cells are central elements of immunologic tolerance. They are abundant in many tumors, where they restrict potentially favorable antitumor responses. We used a three-pronged strategy to identify genes related to the presence and function of Tregs in the tumor microenvironment. Gene expression profiles were generated from tumor-infiltrating Tregs (TITRs) of both human and mouse tumors and were compared with those of Tregs of lymphoid organs or normal tissues from the same individuals. A computational deconvolution of whole-tumor datasets from the Cancer Genome Atlas (TCGA) was performed to identify transcripts specifically associated with Tregs across thousands of tumors from different stages and locations. We identified a set of TITR-differential transcripts with striking reproducibility between tumor types in mice, between mice and humans, and between different human patients spanning tumor stages. Many of the TITR-preferential transcripts were shared with "tissue Tregs" residing in nonlymphoid tissues, but a tumor-preferential segment could be identified. Many of these TITR signature transcripts were confirmed by mining of TCGA datasets, which also brought forth transcript modules likely representing the parenchymal attraction of, or response to, tumor Tregs. Importantly, the TITR signature included several genes encoding effective targets of tumor immunotherapy. A number of other targets were validated by CRISPR-based gene inactivation in mouse Tregs. These results confirm the validity of the signature, generating a wealth of leads for understanding the role of Tregs in tumor progression and identifying potential targets for cancer immunotherapy.}, } @article {pmid30348758, year = {2018}, author = {Grant, PR and Grant, BR}, title = {Role of sexual imprinting in assortative mating and premating isolation in Darwin's finches.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {E10879-E10887}, pmid = {30348758}, issn = {1091-6490}, mesh = {Animals ; Biodiversity ; Biological Evolution ; Ecology ; Ecosystem ; Ecuador ; Finches/genetics/physiology ; *Genetic Speciation ; Hybridization, Genetic/genetics ; Imprinting (Psychology)/*physiology ; Phenotype ; Reproduction/physiology ; Reproductive Isolation ; Sexual Behavior, Animal/*physiology ; Species Specificity ; Vocalization, Animal ; }, abstract = {Global biodiversity is being degraded at an unprecedented rate, so it is important to preserve the potential for future speciation. Providing for the future requires understanding speciation as a contemporary ecological process. Phylogenetically young adaptive radiations are a good choice for detailed study because diversification is ongoing. A key question is how incipient species become reproductively isolated from each other. Barriers to gene exchange have been investigated experimentally in the laboratory and in the field, but little information exists from the quantitative study of mating patterns in nature. Although the degree to which genetic variation underlying mate-preference learning is unknown, we provide evidence that two species of Darwin's finches imprint on morphological cues of their parents and mate assortatively. Statistical evidence of presumed imprinting is stronger for sons than for daughters and is stronger for imprinting on fathers than on mothers. In combination, morphology and species-specific song learned from the father constitute a barrier to interbreeding. The barrier becomes stronger the more the species diverge morphologically and ecologically. It occasionally breaks down, and the species hybridize. Hybridization is most likely to happen when species are similar to each other in adaptive morphological traits, e.g., body size and beak size and shape. Hybridization can lead to the formation of a new species reproductively isolated from the parental species as a result of sexual imprinting. Conservation of sufficiently diverse natural habitat is needed to sustain a large sample of extant biota and preserve the potential for future speciation.}, } @article {pmid30348757, year = {2018}, author = {Sun, YB and Fu, TT and Jin, JQ and Murphy, RW and Hillis, DM and Zhang, YP and Che, J}, title = {Species groups distributed across elevational gradients reveal convergent and continuous genetic adaptation to high elevations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10634-E10641}, pmid = {30348757}, issn = {1091-6490}, abstract = {Although many cases of genetic adaptations to high elevations have been reported, the processes driving these modifications and the pace of their evolution remain unclear. Many high-elevation adaptations (HEAs) are thought to have arisen in situ as populations rose with growing mountains. In contrast, most high-elevation lineages of the Qinghai-Tibetan Plateau appear to have colonized from low-elevation areas. These lineages provide an opportunity for studying recent HEAs and comparing them with ancestral low-elevation alternatives. Herein, we compare four frogs (three species of Nanorana and a close lowland relative) and four lizards (Phrynocephalus) that inhabit a range of elevations on or along the slopes of the Qinghai-Tibetan Plateau. The sequential cladogenesis of these species across an elevational gradient allows us to examine the gradual accumulation of HEA at increasing elevations. Many adaptations to high elevations appear to arise gradually and evolve continuously with increasing elevational distributions. Numerous related functions, especially DNA repair and energy metabolism pathways, exhibit rapid change and continuous positive selection with increasing elevations. Although the two studied genera are distantly related, they exhibit numerous convergent evolutionary changes, especially at the functional level. This functional convergence appears to be more extensive than convergence at the individual gene level, although we found 32 homologous genes undergoing positive selection for change in both high-elevation groups. We argue that species groups distributed along a broad elevational gradient provide a more powerful system for testing adaptations to high-elevation environments compared with studies that compare only pairs of high-elevation versus low-elevation species.}, } @article {pmid30348756, year = {2018}, author = {Hopping, KA and Chignell, SM and Lambin, EF}, title = {The demise of caterpillar fungus in the Himalayan region due to climate change and overharvesting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11489-11494}, pmid = {30348756}, issn = {1091-6490}, abstract = {Demand for traditional medicine ingredients is causing species declines globally. Due to this trade, Himalayan caterpillar fungus (Ophiocordyceps sinensis) has become one of the world's most valuable biological commodities, providing a crucial source of income for hundreds of thousands of collectors. However, the resulting harvesting boom has generated widespread concern over the sustainability of its collection. We investigate whether caterpillar fungus production is decreasing-and if so, why-across its entire range. To overcome the limitations of sparse quantitative data, we use a multiple evidence base approach that makes use of complementarities between local knowledge and ecological modeling. We find that, according to collectors across four countries, caterpillar fungus production has decreased due to habitat degradation, climate change, and especially overexploitation. Our statistical models corroborate that climate change is contributing to this decline. They indicate that caterpillar fungus is more productive under colder conditions, growing in close proximity to areas likely to have permafrost. With significant warming already underway throughout much of its range, we conclude that caterpillar fungus populations have been negatively affected by a combination of overexploitation and climate change. Our results underscore that harvesting is not the sole threat to economically valuable species, and that a collapse of the caterpillar fungus system under ongoing warming and high collection pressure would have serious implications throughout the Himalayan region.}, } @article {pmid30348471, year = {2019}, author = {Theodosopoulos, AN and Hund, AK and Taylor, SA}, title = {Parasites and Host Species Barriers in Animal Hybrid Zones.}, journal = {Trends in ecology & evolution}, volume = {34}, number = {1}, pages = {19-30}, doi = {10.1016/j.tree.2018.09.011}, pmid = {30348471}, issn = {1872-8383}, abstract = {Species barriers are tested in hybrid zones when gene flow occurs between hybridizing species. Hybridization can erode species barriers, lead to the introgression of adaptive traits, or remain stable through time. Outcomes in hybrid zones are influenced by divergence between the hybridizing taxa, behavior, ecology, and geography. Parasites and pathogens play a major role in host fitness and appear to have varied impacts on species barriers in hybrid zones. We comprehensively reviewed the literature on parasitism in animal hybrid zones and present an evolutionary framework within which to consider parasite-hybrid interactions. Parasites most frequently show potential to contribute to species barrier breakdown in hybrid zones, but also frequently show potential to facilitate the maintenance of species barriers. Incorporating eco-immunology, parasite community theory, and spatiotemporal approaches will be important as genomic tools allow researchers to examine parasites and hybrid zones at greater resolution and in a diversity of natural habitats.}, } @article {pmid30348226, year = {2018}, author = {Pittock, A and Hodges, L and Lawrie, SM}, title = {The effectiveness of internet-delivered cognitive behavioural therapy for those with bulimic symptoms: a systematic review : A review of iCBT treatment for bulimic symptoms.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {748}, pmid = {30348226}, issn = {1756-0500}, abstract = {OBJECTIVE: This review looked at internet-delivered cognitive behavioural therapy (iCBT) as a possible treatment for patients with bulimic symptoms. CBT has been established as an effective treatment; however, waiting lists lead to delayed initiation of treatment. iCBT is a possible delivery method to combat this. Medline, EMBASE and PsycInfo were searched for controlled trials using iCBT as a treatment for patients with bulimia nervosa (BN), subthreshold BN or 'eating disorders not otherwise specified' with bulimic characteristics (EDNOS-BN). The literature search returned 482 papers. 5 met the review criteria and were compared in characteristics, methodological quality and outcomes. Outcomes were analysed by calculation of effect sizes; iCBT was evaluated on reduction in binge eating and purging post treatment and at follow-up.

RESULTS: Participants were mostly female with an average age range of 23.7-31 years. 4 studies demonstrated good methodological quality. 1 did not report all of the outcome data, increasing the likelihood of bias. Only 1 study showed widespread benefit over waiting list controls. iCBT was shown to reduce behaviours but was not found to be superior to bibliotherapy or waiting list. Further large-scale studies are required to make conclusive recommendations.}, } @article {pmid30348225, year = {2018}, author = {Buchan, L and St Aubin, CR and Fisher, AL and Hellings, A and Castro, M and Al-Nakkash, L and Broderick, TL and Plochocki, JH}, title = {High-fat, high-sugar diet induces splenomegaly that is ameliorated with exercise and genistein treatment.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {752}, pmid = {30348225}, issn = {1756-0500}, abstract = {OBJECTIVE: We tested the effect of exercise training and genistein treatment on splenomegaly in mice fed a high-fat, high-sugar diet (HFSD).

RESULTS: Male and female C57BL6 mice fed HFSD containing 60% fat along with drinking water containing 42 g/L sugar (55% sucrose/45% fructose) for 12 weeks exhibited significant obesity, hyperglycemia, and elevated plasma IL-6 levels. This was accompanied by splenomegaly characterized by spleen weights 50% larger than mice fed standard chow (P < 0.05) with enlarged rad and white pulps. Mice fed HFSD and treated with a combination of exercise (30 min/day, 5 days/week) and genistein (600 mg genistein/kg diet) had reduced spleen weight (P < 0.05). The decrease in spleen weight was associated with a significant improvement in red-to-white pulp area ratio and plasma glucose and IL-6 (P < 0.05). Our findings indicate that reversal of splenomegaly by regular exercise and genistein treatment may be important in the clinical management of HFSD-induced obesity.}, } @article {pmid30348220, year = {2018}, author = {Akiyama, T and Gregorio, ER and Kobayashi, J}, title = {Youth sports activity and young people's well-being after a disaster: a trial with the Mastery Approach to Coaching (MAC) in the Philippines.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {747}, pmid = {30348220}, issn = {1756-0500}, support = {27A1//The Grant for National Center for Global Health and Medicine/ ; 24590800//JSPS KAKENHI/ ; }, abstract = {OBJECTIVE: Sports activities is broadly utilized to support well-being of youth after a disaster or conflict. However, scientific validation of programs have not been conducted. The Mastery Approach to Coaching (MAC) is a coaching-education program on sports activities. The MAC reported to have a positive effect on youngsters' self-esteem. As self-esteem is generally known to be beneficial for mental status, we tested the effect of a MAC program on students' self-esteem in a disaster-affected area: Leyte, Philippines. We recruited 10th grade students from three schools; one school was allocated to the MAC intervention and the two schools to the control group. All schools were encouraged to involve students in volleyball from January to February 2015. In January 2015, MAC workshop was conducted in the intervention school before the sports activity.

RESULTS: A total of 293 students completed the questionnaires. The intervention school (n = 51) showed a significant change in self-esteem, with the mean score increasing from 20.2 to 21.1 (p = 0.02). Neither school in the control group showed the significant change. The result showed the feasibility and a positive effect of sports activity with the MAC. However, further investigation should be conducted. Trial registration UMIN Clinical Trials Registry ID: UMIN000033197 on June 30th 2018. Retrospectively registered.}, } @article {pmid30348211, year = {2018}, author = {Fissehaye, T and Damte, A and Fantahun, A and Gebrekirstos, K}, title = {Health care seeking behaviour of mothers towards diarrheal disease of children less than 5 years in Mekelle city, North Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {749}, pmid = {30348211}, issn = {1756-0500}, abstract = {OBJECTIVE: To assess the health care seeking behavior of mothers on diarrheal disease of under five children and associated factors in Mekelle City, Northern Ethiopia.

RESULT: This study revealed that 72.5% (n = 58) of the mothers who reported their children had diarrhea had sought health care facilities. Three quarter, (75.9%) of them was seeking health in the public health care facility. Majority, 89.3% of those children who had severe diarrhea sought at health care facilities. In the multivariable analysis, severity of diarrhea (P = 0.04) and blood in stool) were the significantly associated factors with health seeking behavior of mothers for childhood diarrhea.}, } @article {pmid30348204, year = {2018}, author = {Noor, A and Walser, G and Wesseling, M and Giron, P and Laffra, AM and Haddouchi, F and De Grève, J and Kronenberger, P}, title = {Production of a mono-biotinylated EGFR nanobody in the E. coli periplasm using the pET22b vector.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {751}, pmid = {30348204}, issn = {1756-0500}, abstract = {OBJECTIVE: Our aim was to produce a mono-biotinylated single domain antibody ('nanobody') specific for the epidermal growth factor receptor (EGFR), which is overexpressed in many cancer cells. The binding of the nanobody and its function are tested in cancer cells. The construct could be used to carry variable therapeutic or diagnostic load using biotin-streptavidin bridging.

RESULTS: The EGFR-specific 7D12 nanobody was genetically fused to an IgA hinge linker and to a C-terminal biotin ligase acceptor sequence, allowing mono-biotinylation in E. coli. Expression was in strain BL21-DE3 from a T7 RNA polymerase driven pET22b vector. The biotinylated nanobody, isolated from the periplasm, was purified using streptavidin-mutein affinity chromatography. Final yields were up to 5 mg/l of cell culture. We showed that the construct could bind to EGFR expressing A431 epidermoid carcinoma cells, and to transiently transformed EGFR overexpressing HEK293T cells and not to EGFR negative control cells. The specificity for the EGFR was further demonstrated by immunoprecipitation. To test the functionality, PC9 non-small cell lung cancer cells were treated with mono-biotinylated nanobody or with streptavidin-coupled tetravalent nanobodies. Both were able to block mutant EGFR phosphorylation and slow down growth of PC9 cells. Tetravalent nanobodies were able to downregulate AKT phosphorylation.}, } @article {pmid30348201, year = {2018}, author = {Finocchario-Kessler, S and Goggin, K and Staggs, V and Wanyenze, RK and Beyeza-Kashesya, J and Mindry, D and Birungi, J and Wagner, GJ}, title = {High report of miscarriage among women living with HIV who want to conceive in Uganda.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {753}, pmid = {30348201}, issn = {1756-0500}, support = {R01 HD072633/HD/NICHD NIH HHS/United States ; 5R01HD072633-04//National Institute of Child Health and Human Development/ ; }, abstract = {OBJECTIVE: Data on early miscarriage incidence is limited due to various social and methodological barriers. We report on 24-month pregnancy outcomes of 299 female Ugandan HIV clients in committed relationships with an intention to conceive. Miscarriage data are reported as auxiliary findings to a larger study (5R01HD072633).

RESULTS: 127 (42%) participants reported a pregnancy during the study; among the remaining 172, 82 indicated they stopped trying to conceive, and 16 dropped out prior to month 24. Of the 127 pregnancies, 55 (43%) resulted in live births, 67 (53%) in spontaneous miscarriage, 1 (< 1%) in stillbirth, 1 (< 1%) in abortion, and 3 (2%) in unknown outcomes. Three-quarters (75%) of miscarriages for which time until miscarriage was available were reported to occur in the first trimester (mean = 11.3 weeks gestation). The 67 participants who reported a miscarriage tended to be older (mean 33 vs. 30 years), but the significance of age did not persist after adjusting for multiple tests. We observed relatively low rates of pregnancy and high rates of miscarriage among this cohort of HIV-positive women wanting to conceive. Rigorously designed studies are needed to better understand the observed high rate of early miscarriage among HIV-infected women.}, } @article {pmid30348198, year = {2018}, author = {Anson, E and Thompson, E and Karpen, SC and Odle, BL and Seier, E and Jeka, J and Panus, PC}, title = {Visual biofeedback training reduces quantitative drugs index scores associated with fall risk.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {750}, pmid = {30348198}, issn = {1756-0500}, support = {7R21AG041714//National Institutes of Health/ ; T32 DC000023/DC/NIDCD NIH HHS/United States ; Promotion of Doctoral Studies I//Foundation for Physical Therapy/ ; NIDCD T32 DC000023//National Institutes of Health/ ; II Scholarships//Foundation for Physical Therapy/ ; R21 AG041714/AG/NIA NIH HHS/United States ; }, abstract = {OBJECTIVE: Drugs increase fall risk and decrease performance on balance and mobility tests. Conversely, whether biofeedback training to reduce fall risk also decreases scores on a published drug-based fall risk index has not been documented. Forty-eight community-dwelling older adults underwent either treadmill gait training plus visual feedback (+VFB), or walked on a treadmill without feedback. The Quantitative Drug Index (QDI) was derived from each participant's drug list and is based upon all cause drug-associated fall risk. Analysis of covariance assessed changes in the QDI during the study, and data is presented as mean ± standard error of the mean.

RESULTS: The QDI scores decreased significantly (p = 0.031) for participants receiving treadmill gait training +VFB (- 0.259 ± 0.207), compared to participants who walked on the treadmill without VFB (0.463 ± 0.246). Changes in participants QDI scores were dependent in part upon their age, which was a significant covariate (p = 0.007). These preliminary results demonstrate that rehabilitation to reduce fall risk may also decrease use of drugs associated with falls. Determination of which drugs or drug classes that contribute to the reduction in QDI scores for participants receiving treadmill gait training +VFB, compared to treadmill walking only, will require a larger participant investigation. Trial Registration ISRNCT01690611, ClinicalTrials.gov #366151-1, initial 9/24/2012, completed 4/21/2016.}, } @article {pmid30348104, year = {2018}, author = {Roy, A and Sar, P and Sarkar, J and Dutta, A and Sarkar, P and Gupta, A and Mohapatra, B and Pal, S and Kazy, SK}, title = {Petroleum hydrocarbon rich oil refinery sludge of North-East India harbours anaerobic, fermentative, sulfate-reducing, syntrophic and methanogenic microbial populations.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {151}, pmid = {30348104}, issn = {1471-2180}, support = {BT/226/NE/TBP/2011//Department of Biotechnology , Ministry of Science and Technology/ ; }, abstract = {BACKGROUND: Sustainable management of voluminous and hazardous oily sludge produced by petroleum refineries remains a challenging problem worldwide. Characterization of microbial communities of petroleum contaminated sites has been considered as the essential prerequisite for implementation of suitable bioremediation strategies. Three petroleum refinery sludge samples from North Eastern India were analyzed using next-generation sequencing technology to explore the diversity and functional potential of inhabitant microorganisms and scope for their on-site bioremediation.

RESULTS: All sludge samples were hydrocarbon rich, anaerobic and reduced with sulfate as major anion and several heavy metals. High throughput sequencing of V3-16S rRNA genes from sludge metagenomes revealed dominance of strictly anaerobic, fermentative, thermophilic, sulfate-reducing bacteria affiliated to Coprothermobacter, Fervidobacterium, Treponema, Syntrophus, Thermodesulfovibrio, Anaerolinea, Syntrophobacter, Anaerostipes, Anaerobaculum, etc., which have been well known for hydrocarbon degradation. Relatively higher proportions of archaea were detected by qPCR. Archaeal 16S rRNA gene sequences showed presence of methanogenic Methanobacterium, Methanosaeta, Thermoplasmatales, etc. Detection of known hydrocarbon utilizing aerobic/facultative anaerobic (Mycobacterium, Pseudomonas, Longilinea, Geobacter, etc.), nitrate reducing (Gordonia, Novosphigobium, etc.) and nitrogen fixing (Azovibrio, Rhodobacter, etc.) bacteria suggested niche specific guilds with aerobic, facultative anaerobic and strict anaerobic populations. Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) predicted putative genetic repertoire of sludge microbiomes and their potential for hydrocarbon degradation; lipid-, nitrogen-, sulfur- and methane- metabolism. Methyl coenzyme M reductase A (mcrA) and dissimilatory sulfite reductase beta-subunit (dsrB) genes phylogeny confirmed methanogenic and sulfate-reducing activities within sludge environment endowed by hydrogenotrophic methanogens and sulfate-reducing Deltaproteobacteria and Firmicutes members.

CONCLUSION: Refinery sludge microbiomes were comprised of hydrocarbon degrading, fermentative, sulfate-reducing, syntrophic, nitrogen fixing and methanogenic microorganisms, which were in accordance with the prevailing physicochemical nature of the samples. Analysis of functional biomarker genes ascertained the activities of methanogenic and sulfate-reducing organisms within sludge environment. Overall data provided better insights on microbial diversity and activity in oil contaminated environment, which could be exploited suitably for in situ bioremediation of refinery sludge.}, } @article {pmid30348096, year = {2018}, author = {Čermák, V and Fischer, L}, title = {Pervasive read-through transcription of T-DNAs is frequent in tobacco BY-2 cells and can effectively induce silencing.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {252}, pmid = {30348096}, issn = {1471-2229}, support = {LO1417//Ministerstvo Školství, Mládeže a Tělovýchovy/ ; }, mesh = {Agrobacterium tumefaciens/*genetics ; Arabidopsis/*genetics ; Cell Line ; DNA, Bacterial/*genetics ; Genes, Reporter ; Inverted Repeat Sequences/genetics ; Plants, Genetically Modified ; Promoter Regions, Genetic/genetics ; RNA, Messenger/genetics ; Tobacco/*genetics ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Plant transformation via Agrobacterium tumefaciens is characterized by integration of commonly low number of T-DNAs at random positions in the genome. When integrated into an active gene region, promoterless reporter genes placed near the T-DNA border sequence are frequently transcribed and even translated to reporter proteins, which is the principle of promoter- and gene-trap lines.

RESULTS: Here we show that even internal promotorless regions of T-DNAs are often transcribed. Such spontaneous transcription was observed in the majority of independently transformed tobacco BY-2 lines (over 65%) and it could effectively induce silencing if an inverted repeat was present within the T-DNA. We documented that the transcription often occurred in both directions. It was not directly connected with any regulatory elements present within the T-DNAs and at least some of the transcripts were initiated outside of the T-DNA. The likeliness of this read-through transcription seemed to increase in lines with higher T-DNA copy number. Splicing and presence of a polyA tail in the transcripts indicated involvement of Pol II, but surprisingly, the transcription was able to run across two transcription terminators present within the T-DNA. Such pervasive transcription was observed with three different T-DNAs in BY-2 cells and with lower frequency was also detected in Arabidopsis thaliana.

CONCLUSIONS: Our results demonstrate unexpected pervasive read-through transcription of T-DNAs. We hypothesize that it was connected with a specific chromatin state of newly integrated DNA, possibly affected by the adjacent genomic region. Although this phenomenon can be easily overlooked, it can have significant consequences when working with highly sensitive systems like RNAi induction using an inverted repeat construct, so it should be generally considered when interpreting results obtained with the transgenic technology.}, } @article {pmid30348090, year = {2018}, author = {Ren, F and Li, X and Tang, H and Jiang, Q and Yun, X and Fang, L and Huang, P and Tang, Y and Li, Q and Huang, J and Jiao, XA}, title = {Insights into the impact of flhF inactivation on Campylobacter jejuni colonization of chick and mice gut.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {149}, pmid = {30348090}, issn = {1471-2180}, abstract = {BACKGROUND: Campylobacter jejuni (C. jejuni) is a leading cause of foodborne gastroenteritis worldwide. This bacterium lacks many of the classical virulence factors, and flagellum-associated persistent colonization has been shown to be crucial for its pathogenesis. The flagellum plays a multifunctional role in C. jejuni pathogenesis, and different flagellar elements make diverse contributions. The flhF gene encodes the flagellar biosynthesis regulator, which is important for flagellar biosynthesis. In this study, the influence of flhF on C. jejuni colonization was systematically studied, and the possible mechanisms were also analyzed.

RESULTS: The flhF gene has a significant influence on C. jejuni colonization, and its inactivation resulted in severe defects in the commensal colonization of chicks, with approximately 104- to 107-fold reductions (for NCTC 11168 and a C. jejuni isolate respectively) observed in the bacterial caecal loads. Similar effects were observed in mice where the flhF mutant strain completely lost the ability to continuously colonize mice, which cleared the isolate at 7 days post inoculation. Characterization of the phenotypic properties of C. jejuni that influence colonization showed that the adhesion and invasion abilities of the C. jejuni flhF mutant were reduced to approximately 52 and 27% of that of the wild-type strain, respectively. The autoagglutination and biofilm-formation abilities of the flhF mutant strain were also significantly decreased. Further genetic investigation revealed that flhF is continuously upregulated during the infection process, which indicates a close association of this gene with C. jejuni pathogenesis. The transcription of some other infection-related genes that are not directly involved in flagellar assembly were also influenced by its inactivation, with the flagellar coexpressed determinants (Feds) being apparently affected.

CONCLUSIONS: Inactivation of flhF has a significant influence on C. jejuni colonization in both birds and mammals. This defect may be caused by the decreased adhesion, invasion, autoagglutination and biofilm-formation abilities of the flhF mutant strain, as well as the influence on the transcription of other infection related genes, which provides insights into this virulence factor and the flagellum mediated co-regulation of C. jejuni pathogenesis.}, } @article {pmid30348089, year = {2018}, author = {Günther, J and Irmisch, S and Lackus, ND and Reichelt, M and Gershenzon, J and Köllner, TG}, title = {The nitrilase PtNIT1 catabolizes herbivore-induced nitriles in Populus trichocarpa.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {251}, pmid = {30348089}, issn = {1471-2229}, mesh = {Alanine/analogs & derivatives/metabolism ; Aminohydrolases/genetics/*metabolism ; Herbivory ; Nitriles/*metabolism ; Plant Leaves/enzymology/genetics ; Populus/*enzymology/genetics ; }, abstract = {BACKGROUND: Nitrilases are nitrile-converting enzymes commonly found within the plant kingdom that play diverse roles in nitrile detoxification, nitrogen recycling, and phytohormone biosynthesis. Although nitrilases are present in all higher plants, little is known about their function in trees. Upon herbivory, poplars produce considerable amounts of toxic nitriles such as benzyl cyanide, 2-methylbutyronitrile, and 3-methylbutyronitrile. In addition, as byproduct of the ethylene biosynthetic pathway upregulated in many plant species after herbivory, toxic β-cyanoalanine may accumulate in damaged poplar leaves. In this work, we studied the nitrilase gene family in Populus trichocarpa and investigated the potential role of the nitrilase PtNIT1 in the catabolism of herbivore-induced nitriles.

RESULTS: A BLAST analysis revealed three putative nitrilase genes (PtNIT1, PtNIT2, PtNIT3) in the genome of P. trichocarpa. While PtNIT1 was expressed in poplar leaves and showed increased transcript accumulation after leaf herbivory, PtNIT2 and PtNIT3 appeared not to be expressed in undamaged or herbivore-damaged leaves. Recombinant PtNIT1 produced in Escherichia coli accepted biogenic nitriles such as β-cyanoalanine, benzyl cyanide, and indole-3-acetonitrile as substrates in vitro and converted them into the corresponding acids. In addition to this nitrilase activity, PtNIT1 showed nitrile hydratase activity towards β-cyanoalanine, resulting in the formation of the amino acid asparagine. The kinetic parameters of PtNIT1 suggest that the enzyme utilizes β-cyanoalanine and benzyl cyanide as substrates in vivo. Indeed, β-cyanoalanine and benzyl cyanide were found to accumulate in herbivore-damaged poplar leaves. The upregulation of ethylene biosynthesis genes after leaf herbivory indicates that herbivore-induced β-cyanoalanine accumulation is likely caused by ethylene formation.

CONCLUSIONS: Our data suggest a role for PtNIT1 in the catabolism of herbivore-induced β-cyanoalanine and benzyl cyanide in poplar leaves.}, } @article {pmid30348088, year = {2018}, author = {Sinkov, V and Ogarkov, O and Mokrousov, I and Bukin, Y and Zhdanova, S and Heysell, SK}, title = {New epidemic cluster of pre-extensively drug resistant isolates of Mycobacterium tuberculosis Ural family emerging in Eastern Europe.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {762}, pmid = {30348088}, issn = {1471-2164}, support = {R01 DA044137/DA/NIDA NIH HHS/United States ; U01 AI115594/AI/NIAID NIH HHS/United States ; 17-54-30020//Russian Foundation for Basic Research/ ; 5U01AI115594-04//National Institutes of Health/ ; }, mesh = {Drug Resistance, Bacterial/*genetics ; *Epidemics ; Europe/epidemiology ; Genomics ; Genotype ; Humans ; Mycobacterium tuberculosis/drug effects/*genetics/*physiology ; Phylogeny ; Tuberculosis/*epidemiology ; }, abstract = {BACKGROUND: Ural genetic family is a part of the Euro-American lineage of Mycobacterium tuberculosis and is endemic in Northern Eurasia (former Soviet Union [FSU]). These strains were long described as drug susceptible and of low virulence, but recent studies reported an increasing circulation of the multidrug-resistant (MDR) and extensively drug-resistant (XDR) Ural strains. Here, we analyzed all publicly available whole genome sequence data of Ural genotype isolates, in order to elucidate their phylogenomic diversity with a special focus on MDR and potentially epidemic clones.

RESULTS: A total of 149 M. tuberculosis genomes of Ural isolates from FSU countries were mined from the GMTV database and TB-ARC project. We identified 6002 variable amino acid positions that were assessed for functional significance and used to build ML, NJ trees and for Bayesian TMRCA estimation. Three robust monophyletic clades were identified: Clade A (31 isolates from Russia, Belarus, Moldova), Clade B (52 isolates from Russia), and Clade C (37 isolates from Moldova, 2 from Belarus). Clade C was significantly associated with XDR or pre-XDR status compared to the pooled Clades A and B (33/39 versus 5/83, P < 0.0001). Time of origin was estimated for Clade A at 77.7-137 years ago and for Clade B at 56.3-99.2 years ago compared to the significantly more recent origin for Clade C. in silico spoligotyping identified signatures specific of the Clade A (spoligotype SIT35), and Clades B and C (both SIT262).

CONCLUSIONS: A genetically compact and evolutionarily young Ural Clade C, likely originated after collapse of the Soviet Union, and reached epidemic proportions in Moldova in the last 20 years. This epidemic pre-XDR clone (mostly rifampin, isoniazid and kanamycin resistant) is characterized by a specific combination of mutations: KatG Ser315Thr, fabG1 -15C > T, RpoB Ser450Leu, RpsL Lys88Arg, eis -12G > A and EmbB Ser297Ala/T > G. Its further dissemination may occur towards both Russia and European Union and should be taken into consideration by health authorities. The identified spoligotyping signatures can serve for rapid preliminary detection and surveillance of the more hazardous pre-XDR associated strains of the Ural family, both in populations from countries of their endemic circulation and migrant communities.}, } @article {pmid30348086, year = {2018}, author = {Kim, Y and Seo, CW and Khan, AL and Mun, BG and Shahzad, R and Ko, JW and Yun, BW and Park, SK and Lee, IJ}, title = {Exo-ethylene application mitigates waterlogging stress in soybean (Glycine max L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {254}, pmid = {30348086}, issn = {1471-2229}, support = {PJ01367301//Rural Development Administration/ ; }, mesh = {Antioxidants/metabolism ; Ethylenes/metabolism/*pharmacology ; Glutathione/metabolism ; Phenotype ; Photosynthesis/drug effects ; Plant Growth Regulators/*pharmacology ; Plant Roots/drug effects/physiology ; Reactive Nitrogen Species/metabolism ; Reactive Oxygen Species/metabolism ; Soybeans/*drug effects/physiology ; Stress, Physiological/*drug effects ; }, abstract = {BACKGROUND: Waterlogging (WL) is a key factor hindering soybean crop productivity worldwide. Plants utilize various hormones to avoid various stress conditions, including WL stress; however, the physiological mechanisms are still not fully understood.

RESULTS: To identify physiological mechanisms during WL stress, different phytohormones, such as ethephon (ETP; donor source of ethylene), abscisic acid, gibberellins, indole-3-acetic acid, kinetin, jasmonic acid, and salicylic acid were exogenously applied to soybean plants. Through this experiment, we confirmed the beneficial effects of ETP treatment. Thus, we selected ETP as a candidate hormone to mitigate WL. Further mechanistic investigation of the role of ETP in waterlogging tolerance was carried out. Results showed that ETP application mitigated WL stress, significantly improved the photosynthesis pigment, and increased the contents of endogenous GAs compared to those in untreated plants. The amino acid contents during WL stress were significantly activated by EPT treatments. The amino acid contents were significantly higher in the 100 μM ETP-treated soybean plants than in the control. ETP application induced adventitious root initiation, increased root surface area, and significantly increased the expressions of glutathione transferases and relative glutathione activity compared to those of non-ETP-treated plants. ETP-treated soybeans produced a higher up-regulation of protein content and glutathione S-transferase (GSTs) than did soybeans under the WL only treatment.

CONCLUSIONS: In conclusion, the current results suggest that ETP application enabled various biochemical and transcriptional modulations. In particular, ETP application could stimulate the higher expression of GST3 and GST8. Thus, increased GST3 and GST8 induced 1) increased GSH activity, 2) decreased reactive oxygen species (ROS), 3) mitigation of cell damage in photosynthetic apparatus, and 4) improved phenotype consecutively.}, } @article {pmid30348084, year = {2018}, author = {Jenkins, TG and Aston, KI and Cairns, B and Smith, A and Carrell, DT}, title = {Paternal germ line aging: DNA methylation age prediction from human sperm.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {763}, pmid = {30348084}, issn = {1471-2164}, support = {R01 HD082062/HD/NICHD NIH HHS/United States ; R01 HD082062//National Institute of Child Health and Human Development/ ; }, mesh = {Aging/*genetics ; *DNA Methylation ; Environment ; Epigenesis, Genetic ; *Fathers ; Humans ; Male ; Smoking/genetics/physiopathology ; Spermatozoa/*metabolism ; }, abstract = {BACKGROUND: The relationship between aging and epigenetic profiles has been highlighted in many recent studies. Models using somatic cell methylomes to predict age have been successfully constructed. However, gamete aging is quite distinct and as such age prediction using sperm methylomes is ineffective with current techniques.

RESULTS: We have produced a model that utilizes human sperm DNA methylation signatures to predict chronological age by utilizing methylation array data from a total of 329 samples. The dataset used for model construction includes infertile patients, sperm donors, and individuals from the general population. Our model is capable predicting age with an R2 of 0.89, a mean absolute error (MAE) of 2.04 years, and a mean absolute percent error (MAPE) of 6.28% in our data set. We additionally investigated the reproducibility of prediction with our model in an independent cohort where 6 technical replicates of 10 individual samples were tested on different arrays. We found very similar age prediction accuracy (MAE = 2.37 years; MAPE = 7.05%) with a high degree of precision between replicates (standard deviation of only 0.877 years). Additionally, we found that smokers trended toward increased age profiles when compared to 'never smokers' though this pattern was only striking in a portion of the samples screened.

CONCLUSIONS: The predictive model described herein was built to offer researchers the ability to assess "germ line age" by accessing sperm DNA methylation signatures at genomic regions affected by age. Our data suggest that this model can predict an individual's chronological age with a high degree of accuracy regardless of fertility status and with a high degree of repeatability. Additionally, our data suggest that the aging process in sperm may be impacted by environmental factors, though this effect appears to be quite subtle and future work is needed to establish this relationship.}, } @article {pmid30348083, year = {2018}, author = {Mo, Y and Pearce, S and Dubcovsky, J}, title = {Phenotypic and transcriptomic characterization of a wheat tall mutant carrying an induced mutation in the C-terminal PFYRE motif of RHT-B1b.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {253}, pmid = {30348083}, issn = {1471-2229}, support = {2017-67007-25939//National Institute of Food and Agriculture/ ; Continuous support//Howard Hughes Medical Institute/United States ; International Student Research fellowship//Howard Hughes Medical Institute/United States ; International Scholar//Monsanto Beachell-Borlaug/ ; }, mesh = {Alleles ; Amino Acid Motifs ; Cotyledon/genetics/growth & development ; Genotype ; Gibberellins/metabolism ; Mutation, Missense ; Organ Specificity ; Phenotype ; Plant Growth Regulators/metabolism ; Plant Leaves/genetics/growth & development ; Plant Proteins/*genetics ; Plant Shoots/genetics/growth & development ; Plant Stems/genetics/growth & development ; Seedlings/genetics/growth & development ; Sequence Analysis, RNA ; *Transcriptome ; Triticum/*genetics/growth & development ; }, abstract = {BACKGROUND: As central regulators of the gibberellic acid (GA) signaling pathway in plants, DELLA proteins function as growth repressors and affect diverse biological processes. The wheat RHT-B1b and RHT-D1b semi-dwarfing alleles, which encode GA-insensitive DELLA proteins, have been widely adopted in modern wheat varieties to improve lodging tolerance and harvest index. However, the molecular mechanisms by which DELLA modulates these responses in wheat remain largely unknown.

RESULTS: We identified a tall tetraploid wheat mutant line carrying an induced missense mutation (E529K) in the PFYRE motif of RHT-B1b that partially suppressed the semi-dwarf phenotype. The height-increasing effect of RHT-B1bE529K relative to RHT-B1b (19 cm or 21% increase) was significantly smaller than the effect of RHT-B1a (33 cm or 34% increase) relative to RHT-B1b in the same field experiment. The RHT-B1bE529K mutation was also associated with length increases in coleoptiles, seedling shoots, and stem internodes relative to the RHT-B1b allele. We detected no significant differences in germination rate, seedling root length, tiller number, flag leaf size, spike length, or yield components. Using RNA-seq, we compared gene expression profiles of plants encoding RHT-B1b and RHT-B1bE529K in coleoptile, first leaf, and elongating peduncles. We detected limited overlap among tissues of the genes differentially regulated by the two genotypes, and more genes upregulated (77%) than downregulated (23%) in RHT-B1bE529K relative to RHT-B1b. These results suggest that the wheat DELLA protein affects the transcriptome in a tissue-specific manner and that the mutation mainly eliminates or reduces repression functions of the RHT-B1 protein. Our study identified distinct sets of potential DELLA direct or indirect target genes involved in cell wall and carbohydrate metabolisms, cell cycle/division, and hormone pathways.

CONCLUSIONS: We identified the hypomorphic RHT-B1bE529K allele that confers an intermediate plant height and coleoptile elongation. This allele can be useful in rain-fed wheat breeding programs where the strong reduction in height and biomass associated with RHT-B1b has detrimental effects. Transcriptomic characterization of different tissues from the plants encoding RHT-B1bE529K and RHT-B1b provided valuable information for identifying DELLA downstream GA response genes in wheat.}, } @article {pmid30348081, year = {2018}, author = {Langhanki, L and Berger, P and Treffon, J and Catania, F and Kahl, BC and Mellmann, A}, title = {In vivo competition and horizontal gene transfer among distinct Staphylococcus aureus lineages as major drivers for adaptational changes during long-term persistence in humans.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {152}, pmid = {30348081}, issn = {1471-2180}, support = {SFB/TRR34 C7//Deutsche Forschungsgemeinschaft (DE)/ ; SFB/TRR34 C7//Deutsche Forschungsgemeinschaft (DE)/ ; }, abstract = {BACKGROUND: The airways of the majority of adolescent cystic fibrosis (CF) patients are persistently colonized or infected by Staphylococcus aureus. Using whole genome sequencing, we studied the evolutionary traits within a S. aureus population in the airways of a CF patient hypothesizing that horizontal gene transfer (HGT) and inter-bacterial interaction play a major role in adaptation during long-term persistence.

RESULTS: Whole genome sequencing of 21 S. aureus isolates spanning 13 years resulted in seven lineages defined by the spa types t012, t021, t331, t338, t364, t056, and t2351. Of these, the successfully persisting lineages t012 and t021 were closely related suggesting the evolution of t021 from t012, which was further corroborated by a nearly identical, syntenic set of mobile genetic elements. During transformation from t012 to t021, an increase of genomic changes including HGT from other S. aureus lineages was detected.

CONCLUSIONS: In summary, our in vivo data enabled us to conceptualize an evolutionary model showing the impact of HGT and inter-bacterial interaction on bacterial long-term adaptation to the human host during CF.}, } @article {pmid30348080, year = {2018}, author = {Paijmans, JLA and Barlow, A and Förster, DW and Henneberger, K and Meyer, M and Nickel, B and Nagel, D and Worsøe Havmøller, R and Baryshnikov, GF and Joger, U and Rosendahl, W and Hofreiter, M}, title = {Historical biogeography of the leopard (Panthera pardus) and its extinct Eurasian populations.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {156}, pmid = {30348080}, issn = {1471-2148}, mesh = {Animals ; Asia ; Calibration ; DNA, Mitochondrial/genetics ; Europe ; *Extinction, Biological ; Genome, Mitochondrial ; Panthera/*classification/genetics ; Phylogeny ; *Phylogeography ; }, abstract = {BACKGROUND: Resolving the historical biogeography of the leopard (Panthera pardus) is a complex issue, because patterns inferred from fossils and from molecular data lack congruence. Fossil evidence supports an African origin, and suggests that leopards were already present in Eurasia during the Early Pleistocene. Analysis of DNA sequences however, suggests a more recent, Middle Pleistocene shared ancestry of Asian and African leopards. These contrasting patterns led researchers to propose a two-stage hypothesis of leopard dispersal out of Africa: an initial Early Pleistocene colonisation of Asia and a subsequent replacement by a second colonisation wave during the Middle Pleistocene. The status of Late Pleistocene European leopards within this scenario is unclear: were these populations remnants of the first dispersal, or do the last surviving European leopards share more recent ancestry with their African counterparts?

RESULTS: In this study, we generate and analyse mitogenome sequences from historical samples that span the entire modern leopard distribution, as well as from Late Pleistocene remains. We find a deep bifurcation between African and Eurasian mitochondrial lineages (~ 710 Ka), with the European ancient samples as sister to all Asian lineages (~ 483 Ka). The modern and historical mainland Asian lineages share a relatively recent common ancestor (~ 122 Ka), and we find one Javan sample nested within these.

CONCLUSIONS: The phylogenetic placement of the ancient European leopard as sister group to Asian leopards suggests that these populations originate from the same out-of-Africa dispersal which founded the Asian lineages. The coalescence time found for the mitochondrial lineages aligns well with the earliest undisputed fossils in Eurasia, and thus encourages a re-evaluation of the identification of the much older putative leopard fossils from the region. The relatively recent ancestry of all mainland Asian leopard lineages suggests that these populations underwent a severe population bottleneck during the Pleistocene. Finally, although only based on a single sample, the unexpected phylogenetic placement of the Javan leopard could be interpreted as evidence for exchange of mitochondrial lineages between Java and mainland Asia, calling for further investigation into the evolutionary history of this subspecies.}, } @article {pmid30348079, year = {2018}, author = {Gurgul, A and Jasielczuk, I and Ropka-Molik, K and Semik-Gurgul, E and Pawlina-Tyszko, K and Szmatoła, T and Szyndler-Nędza, M and Bugno-Poniewierska, M and Blicharski, T and Szulc, K and Skrzypczak, E and Krupiński, J}, title = {A genome-wide detection of selection signatures in conserved and commercial pig breeds maintained in Poland.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {95}, pmid = {30348079}, issn = {1471-2156}, support = {BIOSTRATEG2/297267/14/NCBR/2016//National Research and Development Center (Poland)/ ; }, abstract = {BACKGROUND: Identification of selection signatures can provide a direct insight into the mechanism of artificial selection and allow further disclosure of the candidate genes related to the animals' phenotypic variation. Domestication and subsequent long-time selection have resulted in extensive phenotypic changes in domestic pigs, involving a number of traits, like behavior, body composition, disease resistance, reproduction and coat color. In this study, based on genotypes obtained from PorcineSNP60 Illumina assay we attempt to detect both diversifying and within-breed selection signatures in 530 pigs belonging to four breeds: Polish Landrace, Puławska, Złotnicka White and Złotnicka Spotted, of which the last three are a subject of conservative breeding and substantially represent the native populations.

RESULTS: A two largely complementary statistical methods were used for signatures detection, including: pairwise FST and relative extended haplotype homozygosity (REHH) test. Breed-specific diversifying selection signals included several genes involved in processes connected with fertility, growth and metabolism which are potentially responsible for different phenotypes of the studied breeds. The diversifying selection signals also comprised PPARD gene that was previously found to have a large effect on the shape of the external ear in pigs or two genes encoding neuropeptide Y receptors (Y2 and Y5) involved in fat deposition and stress response which are important features differentiating the studied breeds. REHH statistics allowed detecting several within-breed selection signatures overlapping with genes connected with a range of functions including, among others: metabolic pathways, immune system response or implantation and development of the embryo.

CONCLUSIONS: The study provides many potential candidate genes with implication for traits selected in the individual breeds and gives strong basis for further studies aiming at identification of sources of variation among the studied pig breeds.}, } @article {pmid30348078, year = {2018}, author = {Ogura, A and Akizuki, Y and Imoda, H and Mineta, K and Gojobori, T and Nagai, S}, title = {Comparative genome and transcriptome analysis of diatom, Skeletonema costatum, reveals evolution of genes for harmful algal bloom.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {765}, pmid = {30348078}, issn = {1471-2164}, support = {KAUST//King Abdullah University of Science and Technology/ ; Science and Technology Research Partnership for sustainable Development//Japan Science and Technology Agency/ ; }, mesh = {Diatoms/*genetics/*growth & development/metabolism ; *Evolution, Molecular ; *Gene Expression Profiling ; *Genomics ; *Harmful Algal Bloom ; Silicates/metabolism ; }, abstract = {BACKGROUND: Diatoms play a great role in carbon fixation with about 20% of the whole fixation in the world. However, harmful algal bloom as known as red tide is a major problem in environment and fishery industry. Even though intensive studies have been conducted so far, the molecular mechanism behind harmful algal bloom was not fully understood. There are two major diatoms have been sequenced, but more diatoms should be examined at the whole genome level, and evolutionary genome studies were required to understand the landscape of molecular mechanism of the harmful algal bloom.

RESULTS: Here we sequenced the genome of Skeletonema costatum, which is the dominant diatom in Japan causing a harmful algal bloom, and also performed RNA-sequencing analysis for conditions where harmful algal blooms often occur. As results, we found that both evolutionary genomic and comparative transcriptomic studies revealed genes for oxidative stress response and response to cytokinin is a key for the proliferation of the diatom.

CONCLUSIONS: Diatoms causing harmful algal blooms have gained multi-copy of genes related to oxidative stress response and response to cytokinin and obtained an ability to intensive gene expression at the blooms.}, } @article {pmid30348075, year = {2018}, author = {Wong, TKF and Ranjard, L and Lin, Y and Rodrigo, AG}, title = {HaploJuice : accurate haplotype assembly from a pool of sequences with known relative concentrations.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {389}, pmid = {30348075}, issn = {1471-2105}, support = {DP160103474//Australian Research Council (AU)/ ; }, mesh = {*Algorithms ; Base Sequence ; Computer Simulation ; Databases, Genetic ; Haplotypes/*genetics ; Humans ; }, abstract = {BACKGROUND: Pooling techniques, where multiple sub-samples are mixed in a single sample, are widely used to take full advantage of high-throughput DNA sequencing. Recently, Ranjard et al. (PLoS ONE 13:0195090, 2018) proposed a pooling strategy without the use of barcodes. Three sub-samples were mixed in different known proportions (i.e. 62.5%, 25% and 12.5%), and a method was developed to use these proportions to reconstruct the three haplotypes effectively.

RESULTS: HaploJuice provides an alternative haplotype reconstruction algorithm for Ranjard et al.'s pooling strategy. HaploJuice significantly increases the accuracy by first identifying the empirical proportions of the three mixed sub-samples and then assembling the haplotypes using a dynamic programming approach. HaploJuice was evaluated against five different assembly algorithms, Hmmfreq (Ranjard et al., PLoS ONE 13:0195090, 2018), ShoRAH (Zagordi et al., BMC Bioinformatics 12:119, 2011), SAVAGE (Baaijens et al., Genome Res 27:835-848, 2017), PredictHaplo (Prabhakaran et al., IEEE/ACM Trans Comput Biol Bioinform 11:182-91, 2014) and QuRe (Prosperi and Salemi, Bioinformatics 28:132-3, 2012). Using simulated and real data sets, HaploJuice reconstructed the true sequences with the highest coverage and the lowest error rate.

CONCLUSION: HaploJuice provides high accuracy in haplotype reconstruction, making Ranjard et al.'s pooling strategy more efficient, feasible, and applicable, with the benefit of reducing the sequencing cost.}, } @article {pmid30348074, year = {2018}, author = {Kin, K and Forbes, G and Cassidy, A and Schaap, P}, title = {Cell-type specific RNA-Seq reveals novel roles and regulatory programs for terminally differentiated Dictyostelium cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {764}, pmid = {30348074}, issn = {1471-2164}, support = {742288//H2020 European Research Council/ ; ALTF 295-2015//European Molecular Biology Organization/ ; H28-1002//Japan Society for the Promotion of Science/ ; }, mesh = {Dictyostelium/*cytology/*genetics/metabolism ; Gene Expression Regulation ; Gene Ontology ; Metabolic Networks and Pathways/genetics ; RNA, Protozoan/*genetics ; *Sequence Analysis, RNA ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: A major hallmark of multicellular evolution is increasing complexity by the evolution of new specialized cell types. During Dictyostelid evolution novel specialization occurred within taxon group 4. We here aim to retrace the nature and ancestry of the novel "cup" cells by comparing their transcriptome to that of other cell types.

RESULTS: RNA-Seq was performed on purified mature spore, stalk and cup cells and on vegetative amoebas. Clustering and phylogenetic analyses showed that cup cells were most similar to stalk cells, suggesting that they share a common ancestor. The affinity between cup and stalk cells was also evident from promoter-reporter studies of newly identified cell-type genes, which revealed late expression in cups of many stalk genes. However, GO enrichment analysis reveal the unexpected prominence of GTPase mediated signalling in cup cells, in contrast to enrichment of autophagy and cell wall synthesis related transcripts in stalk cells. Combining the cell type RNA-Seq data with developmental expression profiles revealed complex expression dynamics in each cell type as well as genes exclusively expressed during terminal differentiation. Most notable were nine related hssA-like genes that were highly and exclusively expressed in cup cells.

CONCLUSIONS: This study reveals the unique transcriptomes of the mature cup, stalk and spore cells of D. discoideum and provides insight into the ancestry of cup cells and roles in signalling that were not previously realized. The data presented in this study will serve as an important resource for future studies into the regulation and evolution of cell type specialization.}, } @article {pmid30347238, year = {2019}, author = {de Sá, RO and Tonini, JFR and van Huss, H and Long, A and Cuddy, T and Forlani, MC and Peloso, PLV and Zaher, H and Haddad, CFB}, title = {Multiple connections between Amazonia and Atlantic Forest shaped the phylogenetic and morphological diversity of Chiasmocleis Mehely, 1904 (Anura: Microhylidae: Gastrophryninae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {198-210}, doi = {10.1016/j.ympev.2018.10.021}, pmid = {30347238}, issn = {1095-9513}, abstract = {Chiasmocleis is the most species-rich genus of Neotropical microhylids. Herein, we provide the first comprehensive multilocus phylogeny for the genus, including all but 3 of the 34 recognized species and multiple individuals per species. We discuss cryptic speciation, species discovery, patterns of morphological evolution, and provide a historical biogeographic analysis to account for the current distribution of the genus. Diversification of Chiasmocleis from other New World microhylids began during the Eocene, app. 40 mya, in forested areas, and current diversity seems to be a product of recurrent connections between the Atlantic Forest and Amazonia. Small-sized species evolved independently three times in Chiasmocleis. Furthermore, the extremely small-bodied (i.e. miniaturized) species with associated loss of digits, phalanges, and pectoral girdle cartilages evolved only once and are restricted to Amazonia. Using the phylogeny, we recognized three subgenera within Chiasmocleis: Chiasmocleis Méhely, 1904, Relictus subg. nov., and Syncope Walker, 1973. The recognition of the subgenus Syncope informs future research on patterns of miniaturization in the genus, and the subgenus Relictus highlights isolation of an endemic and species-poor lineage to the Atlantic Forest, early (about 40 mya) in the history of Chiasmocleis.}, } @article {pmid30347187, year = {2018}, author = {Meserve, JH and Duronio, RJ}, title = {Fate mapping during regeneration: Cells that undergo compensatory proliferation in damaged Drosophila eye imaginal discs differentiate into multiple retinal accessory cell types.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {43-49}, pmid = {30347187}, issn = {1095-564X}, support = {R01 DA036897/DA/NIDA NIH HHS/United States ; R01 GM057859/GM/NIGMS NIH HHS/United States ; R01 GM058921/GM/NIGMS NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; F31 AG044957/AG/NIA NIH HHS/United States ; R01 GM124201/GM/NIGMS NIH HHS/United States ; }, abstract = {Regeneration of tissues that have been damaged by cell loss requires new growth, often via proliferation of precursor cells followed by differentiation to replace loss of specific cell types. When regeneration occurs after normal differentiation of the tissue is complete, developmental pathways driving differentiation must be re-activated. How proliferation and differentiation are induced and balanced during regeneration is not well understood. To investigate these processes, we utilized a paradigm for tissue damage and regeneration in the developing Drosophila melanogaster eye. Previous studies have demonstrated that tissue damage resulting from extensive cell death stimulates quiescent, undifferentiated cells in the developing larval eye to re-enter the cell cycle and proliferate. Whether these cells are restricted to certain fates or can contribute to all retinal cell types and thus potentially be fully regenerative is not known. Here we found by fate mapping experiments that these cells are competent to differentiate into all accessory cell types in the retina but do not differentiate into photoreceptors, likely because cell cycle re-entry in response to damage occurs after photoreceptor differentiation has completed. We conclude that the ability to re-enter the cell cycle in response to tissue damage in the developing Drosophila eye is not restricted to precursors of a specific cell type and that cell cycle re-entry following damage does not disrupt developmental programs that control differentiation.}, } @article {pmid30347186, year = {2018}, author = {Ravanelli, AM and Kearns, CA and Powers, RK and Wang, Y and Hines, JH and Donaldson, MJ and Appel, B}, title = {Sequential specification of oligodendrocyte lineage cells by distinct levels of Hedgehog and Notch signaling.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {93-106}, pmid = {30347186}, issn = {1095-564X}, support = {R01 NS046668/NS/NINDS NIH HHS/United States ; P30 NS048154/NS/NINDS NIH HHS/United States ; }, abstract = {During development of the central nervous system oligodendrocyte precursor cells (OPCs) give rise to both myelinating oligodendrocytes and NG2 glia, which are the most proliferative cells in the adult mammalian brain. NG2 glia retain characteristics of OPCs, and some NG2 glia produce oligodendrocytes, but many others persist throughout adulthood. Why some OPCs differentiate as oligodendrocytes during development whereas others persist as OPCs and acquire characteristics of NG2 glia is not known. Using zebrafish spinal cord as a model, we found that OPCs that differentiate rapidly as oligodendrocytes and others that remain as OPCs arise in sequential waves from distinct neural progenitors. Additionally, oligodendrocyte and persistent OPC fates are specified during a defined critical period by small differences in Shh signaling and Notch activity, which modulates Shh signaling response. Thus, our data indicate that OPCs fated to produce oligodendrocytes or remain as OPCs during development are specified as distinct cell types, raising the possibility that the myelinating potential of OPCs is set by graded Shh signaling activity.}, } @article {pmid30346661, year = {2018}, author = {Zanardini, E and May, E and Purdy, KJ and Murrell, JC}, title = {Nutrient cycling potential within microbial communities on culturally important stoneworks.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12707}, pmid = {30346661}, issn = {1758-2229}, support = {PIEF-GA-2009-235317//FP7 People: Marie-Curie Actions/ ; NE/J024503/1//Natural Environment Research Council/ ; }, abstract = {Previous studies on microbes associated with deterioration of cultural heritage (CH) stoneworks have revealed a diverse microbiota adapted to stresses such as low nutrients, aridity and high salinity, temperatures and radiation. However, the function of these pioneer microbial communities is still unclear. This study examines bacterial and archaeal diversity in exfoliated and dark encrustation sandstone from Portchester Castle (UK) by 16S rRNA and functional gene analyses. Bacterial and archaeal communities from the exfoliated sites were distinctly different from the dark encrustation. Detected genera were linked to extreme environmental conditions, various potential functional roles and degradation abilities. From these data it was possible to reconstruct almost complete nitrogen and sulfur cycles, as well as autotrophic carbon fixation and mineral transformation processes. Analysis of RNA showed that many of the detected genera in these nutrient cycles were probably active in situ. Thus, CH stonework microbial communities are highly diverse and potentially self-sustaining ecosystems capable of cycling carbon, nitrogen and sulfur as well as the stone biodeterioration processes that lead to alterations such as exfoliation and corrosion. These results highlight the importance of diversity and internal recycling capacity in the development of microbial communities in harsh and low energy systems.}, } @article {pmid30346656, year = {2018}, author = {Henríquez, T and Stein, NV and Jung, H}, title = {PvdRT-OpmQ and MdtABC-OpmB efflux systems are involved in pyoverdine secretion in Pseudomonas putida KT2440.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12708}, pmid = {30346656}, issn = {1758-2229}, support = {SPP1617 (JU 333/5-1, 2)//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Fluorescent pseudomonads produce and secrete a siderophore termed pyoverdine to capture iron when it becomes scarce. The molecular basis of pyoverdine secretion is only partially understood. Here, we investigate the role of the putative PvdRT-OpmQ and MdtABC-OpmB efflux systems in pyoverdine secretion in the soil bacterium Pseudomonas putida KT2440. Expression from the respective promoters is stimulated by iron limitation albeit to varying degrees. Deletion of pvdRT-opmQ leads to reduced amounts of pyoverdine in the medium and decreased growth under iron limitation. Deletion of mdtABC-opmB does not affect growth. However, when both systems are deleted, strong effects on growth and pyoverdine secretion (yellow colony phenotype, less pyoverdine in medium, more pyoverdine in the periplasm) are observed. Overexpression of pvdRT-opmQ causes the opposite effect. These results provide first evidence for an involvement of the multidrug efflux system MdtABC-OpmB in pyoverdine secretion. In addition, the PvdRT-OpmQ system was shown to contribute to pyoverdine secretion in P. putida KT2440, extending previous investigations on its role in Pseudomonas species. Since the double deletion mutant still secrets pyoverdine, at least one additional efflux system participates in the transport of the siderophore. Furthermore, our results suggest a contribution of both efflux systems to ampicillin resistance.}, } @article {pmid30346651, year = {2018}, author = {Erdmann, J and Preusse, M and Khaledi, A and Pich, A and Häussler, S}, title = {Environment-driven changes of mRNA and protein levels in Pseudomonas aeruginosa.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3952-3963}, doi = {10.1111/1462-2920.14419}, pmid = {30346651}, issn = {1462-2920}, support = {1616038C//German Federal Ministry of Education and Research/ ; 724290//European Research Council/International ; }, abstract = {Systems biology approaches address the challenge of translating sequence information into function. In this study, we described the Pseudomonas aeruginosa PA14 proteomic landscape and quantified environment-driven changes in protein levels by the use of LC-MS techniques. Previously recorded mRNA data allowed a comparison of RNA to protein ratios for each individual gene and, thus, to explore the relationship between an mRNA being differentially expressed between environmental conditions and the mRNA-protein correlation for that gene. We developed a Random Forest-based predictor for protein levels and found that the mRNA to protein correlation was higher for genes/proteins that undergo dynamic changes. One example of a discrepancy between protein and predicted protein levels was observed for a phage-related gene cluster, which was translated into low protein levels under standard growth conditions. However, under SOS-inducing conditions more protein was produced and the prediction of protein levels based on mRNA abundancy became more accurate. In conclusion, our systems biology approach sheds light on complex mRNA to protein level relationships and uncovered condition-dependent post-transcriptional regulatory events.}, } @article {pmid30346649, year = {2019}, author = {Wang, Q and Liu, H and Xu, H and Hei, R and Zhang, S and Jiang, C and Xu, JR}, title = {Independent losses and duplications of autophagy-related genes in fungal tree of life.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {226-243}, doi = {10.1111/1462-2920.14451}, pmid = {30346649}, issn = {1462-2920}, support = {2017YFD0200602-2//National Key R&D Program of China/ ; 31701747//National Natural Science Foundation of China/ ; 31601587//National Natural Science Foundation of China/ ; 2015M580884//China Postdoctoral Science Foundation/ ; 201471//National Excellent Doctoral Dissertations/ ; //US Wheat and Barley Scab Initiative/ ; }, abstract = {Autophagy is important for growth, development and pathogenesis in fungi. Although autophagic process is generally considered to be conserved, the conservation and evolution of ATG genes at kingdom-wide remains to be conducted. Here we systematically identified 41 known ATG genes in 331 species and analyzed their distribution across the fungal kingdom. In general, only 20 ATG genes are highly conserved, including most but not all the yeast core-autophagy-machinery genes. Four functional protein groups involved in autophagosome formation had conserved and non-conserved components, suggesting plasticity in autophagosome formation in fungi. All or majority of the key ATG genes were lost in several fungal groups with unique lifestyles and niches, such as Microsporidia, Pneumocystis and Malassezia. Moreover, majority of ATG genes had A-to-I RNA editing during sexual reproduction in two ascomycetes and deletion of FgATG11, the ATG gene with the most editing sites in Fusarium affected ascospore releasing. Duplication and divergence also was observed to several core ATG genes, such as highly divergent ATG8 paralogs in dermatophytes and multiple ATG15 duplications in mushrooms. Taken together, independent losses and duplications of ATG genes have occurred throughout the fungal kingdom and variations in autophagy exist among different lineages and possibly different developmental stages.}, } @article {pmid30346633, year = {2019}, author = {Castledine, M and Buckling, A and Padfield, D}, title = {A shared coevolutionary history does not alter the outcome of coalescence in experimental populations of Pseudomonas fluorescens.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {58-65}, doi = {10.1111/jeb.13394}, pmid = {30346633}, issn = {1420-9101}, support = {//Natural Environment Research Council/ ; }, abstract = {Community coalescence, the mixing of multiple communities, is ubiquitous in natural microbial communities. During coalescence, theory suggests the success of a population will be enhanced by the presence of species it has coevolved with (relative to foreign species), because coevolution will result in greater resource specialization to minimize competition. Thus, more coevolved communities should dominate over less coevolved communities during coalescence events. We test these hypotheses using the bacterium Pseudomonas fluorescens which diversifies into coexisting niche-specialist morphotypes. We first evolved replicate populations for ~40 generations and then isolated evolved genotypes. In a series of competition trials, we determined if using coevolved versus random genotypes affected the relative performance of "communities" of single and multiple genotypes. We found no effect of coevolutionary history on either genotype fitness or community performance, which suggests parallel (co)evolution between communities. However, fitness was enhanced by the presence of other genotypes of the same strain type (wild-type or an isogenic strain with a LacZ marker; the inclusion of the latter necessary to distinguish genotypes during competition), indicative of local adaptation with respect to genetic background. Our results are the first to investigate the effect of (co)evolution on the outcome of coalescence and suggest that when input populations are functionally similar and added at equal mixing ratios, the outcome community may not be asymmetrically dominated by either input population.}, } @article {pmid30346520, year = {2018}, author = {Gutiérrez, R and Markus, B and Carstens Marques de Sousa, K and Marcos-Hadad, E and Mugasimangalam, RC and Nachum-Biala, Y and Hawlena, H and Covo, S and Harrus, S}, title = {Prophage-Driven Genomic Structural Changes Promote Bartonella Vertical Evolution.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3089-3103}, pmid = {30346520}, issn = {1759-6653}, abstract = {Bartonella is a genetically diverse group of vector-borne bacteria. Over 40 species have been characterized to date, mainly from mammalian reservoirs and arthropod vectors. Rodent reservoirs harbor one of the largest Bartonella diversity described to date, and novel species and genetic variants are continuously identified from these hosts. Yet, it is still unknown if this significant genetic diversity stems from adaptation to different niches or from intrinsic high mutation rates. Here, we explored the vertical occurrence of spontaneous genomic alterations in 18 lines derived from two rodent-associated Bartonella elizabethae-like strains, evolved in nonselective agar plates under conditions mimicking their vector- and mammalian-associated temperatures, and the transmission cycles between them (i.e., 26 °C, 37 °C, and alterations between the two), using mutation accumulation experiments. After ∼1,000 generations, evolved genomes revealed few point mutations (average of one-point mutation per line), evidencing conserved single-nucleotide mutation rates. Interestingly, three large structural genomic changes (two large deletions and an inversion) were identified over all lines, associated with prophages and surface adhesin genes. Particularly, a prophage, deleted during constant propagation at 37 °C, was associated with an increased autonomous replication at 26 °C (the flea-associated temperature). Complementary molecular analyses of wild strains, isolated from desert rodents and their fleas, further supported the occurrence of structural genomic variations and prophage-associated deletions in nature. Our findings suggest that structural genomic changes represent an effective intrinsic mechanism to generate diversity in slow-growing bacteria and emphasize the role of prophages as promoters of diversity in nature.}, } @article {pmid30346517, year = {2018}, author = {Casola, C}, title = {From De Novo to "De Nono": The Majority of Novel Protein-Coding Genes Identified with Phylostratigraphy Are Old Genes or Recent Duplicates.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2906-2918}, pmid = {30346517}, issn = {1759-6653}, abstract = {The evolution of novel protein-coding genes from noncoding regions of the genome is one of the most compelling pieces of evidence for genetic innovations in nature. One popular approach to identify de novo genes is phylostratigraphy, which consists of determining the approximate time of origin (age) of a gene based on its distribution along a species phylogeny. Several studies have revealed significant flaws in determining the age of genes, including de novo genes, using phylostratigraphy alone. However, the rate of false positives in de novo gene surveys, based on phylostratigraphy, remains unknown. Here, I reanalyze the findings from three studies, two of which identified tens to hundreds of rodent-specific de novo genes adopting a phylostratigraphy-centered approach. Most putative de novo genes discovered in these investigations are no longer included in recently updated mouse gene sets. Using a combination of synteny information and sequence similarity searches, I show that ∼60% of the remaining 381 putative de novo genes share homology with genes from other vertebrates, originated through gene duplication, and/or share no synteny information with nonrodent mammals. These results led to an estimated rate of ∼12 de novo genes per million years in mouse. Contrary to a previous study (Wilson BA, Foy SG, Neme R, Masel J. 2017. Young genes are highly disordered as predicted by the preadaptation hypothesis of de novo gene birth. Nat Ecol Evol. 1:0146), I found no evidence supporting the preadaptation hypothesis of de novo gene formation. Nearly half of the de novo genes confirmed in this study are within older genes, indicating that co-option of preexisting regulatory regions and a higher GC content may facilitate the origin of novel genes.}, } @article {pmid30346514, year = {2018}, author = {Bansal, K and Kumar, S and Patil, PB}, title = {Complete Genome Sequence Reveals Evolutionary Dynamics of an Emerging and Variant Pathovar of Xanthomonas euvesicatoria.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3104-3109}, pmid = {30346514}, issn = {1759-6653}, abstract = {Xanthomonas, a complex group of pathogens, infects more than 400 plants, which is expanding to new hosts causing serious diseases. Genome-based studies are transforming our understanding on diversity and relationship of host-specific members, known as pathovars. In this study, we report complete genome sequence of a novel pathovar Xanthomonas axonopodis pv. commiphorae (Xcom) from India. It causes gumming disease of Commiphora wightii, a medicinally important plant. Genome-based phylogenetic and taxonomic investigation revealed that the pathovar belongs to Xanthomonas euvesicatoria and not X. axonopodis as reported earlier. Interestingly, it is a novel host and novel geographic origin for a X. euvesicatoria pathovar. A core-genome-based phylogenetic analysis resolved the pathovar complex of this species on the basis of their hosts. Interestingly, this pathovar harbors a unique 35-kb plasmid encoding type III effectors and toxin-antitoxin gene that is absent in other X. euvesicatoria pathovars and infects tomato, pepper, rose, onion, philodendron, alfalfa, and citrus plants. The pathovar contains two TAL (transcription activator-like) genes, one on plasmid and another on genomic region with an additional pseudo TAL gene flanked by IS elements in the plasmid. Further, Xcom has acquired a novel set of lipopolysaccharide biosynthesis genes after its divergence from the closely related pathovar that infects rose and supports the role of horizontal gene transfer in hypervariation at this locus in the species. Complete genome sequence of this variant pathovar has provided novel insights into evolution of an emerging pathovar in Xanthomonas and will be valuable resource in pathogenomics of X. euvesicatoria.}, } @article {pmid30346031, year = {2018}, author = {Touchon, JC and Robertson, JM}, title = {You cannot have it all: Heritability and constraints of predator-induced developmental plasticity in a Neotropical treefrog.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2758-2772}, doi = {10.1111/evo.13632}, pmid = {30346031}, issn = {1558-5646}, support = {DEB-0506043//Division of Environmental Biology/ ; DEB-0508811//Division of Environmental Biology/ ; //Smithsonian Tropical Research Institute/ ; //Boston University/ ; //Cornell University/ ; }, abstract = {Many organisms have evolved phenotypic plasticity but examples of a heritable genetic basis or genetic constraints for plasticity across environments remain scarce. Tadpoles of the Neotropical treefrog Dendropsophus ebraccatus alter tail coloration and shape differently in response to fish or aquatic insect predators. To assess the genetic basis of plasticity we raised 1020 tadpoles from 17 maternal half-sib pairs (34 unique families) individually with chemical cues of fish or aquatic insects, or with cue-free control water. We used Bayesian animal models to estimate narrow sense heritability of morphology and cross-trait genetic correlations in all three treatments, heritability of plasticity in response to each predator, and genetic correlations between responses to fish and insects. Families showed remarkably different responses to predators and heritability was often high (0.45-0.75), as was heritability of plasticity itself (0.42-0.62). We detected strong negative genetic correlations for responses to each predator (-0.45 and -0.59), providing clear evidence of a limit to plasticity. Most importantly, we show that prey genotypes are constrained in their capacity to respond to different types of predators, which likely maintains genetic variation for plasticity in a temporally and spatially dynamic landscape where there is no single adaptive peak.}, } @article {pmid30344890, year = {2018}, author = {Faye, P and Bertrand, C and Pédron, J and Barny, MA}, title = {Draft genomes of "Pectobacterium peruviense" strains isolated from fresh water in France.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {27}, pmid = {30344890}, issn = {1944-3277}, abstract = {Bacteria belonging to the genus Pectobacterium are responsible for soft rot disease on a wide range of cultivated crops. The "Pectobacterium peruviense" specie, recently proposed inside the Pectobacterium genus, gathers strains isolated from potato tubers cultivated in Peru at high altitude. Here we report the draft genome sequence of two strains belonging to "P. peruviense" isolated from river water in France indicating that the geographic distribution of this specie is likely to be larger than previously anticipated. We compared these genomes with the one published from the "P. peruviense" specie type strain isolated in Peru.}, } @article {pmid30344889, year = {2018}, author = {Fuentes-Valdés, JJ and Soto-Liebe, K and Pérez-Pantoja, D and Tamames, J and Belmar, L and Pedrós-Alió, C and Garrido, D and Vásquez, M}, title = {Draft genome sequences of Cylindrospermopsis raciborskii strains CS-508 and MVCC14, isolated from freshwater bloom events in Australia and Uruguay.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {26}, pmid = {30344889}, issn = {1944-3277}, abstract = {Members of the genus Cylindrospermopsis represent an important environmental and health concern. Strains CS-508 and MVCC14 of C. raciborskii were isolated from freshwater reservoirs located in Australia and Uruguay, respectively. While CS-508 has been reported as non-toxic, MVCC14 is a saxitoxin (STX) producer. We annotated the draft genomes of these C. raciborskii strains using the assembly of reads obtained from Illumina MiSeq sequencing. The final assemblies resulted in genome sizes close to 3.6 Mbp for both strains and included 3202 ORFs for CS-508 (in 163 contigs) and 3560 ORFs for MVCC14 (in 99 contigs). Finally, both the average nucleotide identity (ANI) and the similarity of gene content indicate that these two genomes should be considered as strains of the C. raciborskii species.}, } @article {pmid30344888, year = {2018}, author = {Daas, MS and Rosana, ARR and Acedo, JZ and Douzane, M and Nateche, F and Kebbouche-Gana, S and Vederas, JC}, title = {Insights into the draft genome sequence of bioactives-producing Bacillus thuringiensis DNG9 isolated from Algerian soil-oil slough.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {25}, pmid = {30344888}, issn = {1944-3277}, abstract = {Bacillus thuringiensis is widely used as a bioinsecticide due to its ability to form parasporal crystals containing proteinaceous toxins. It is a member of the Bacillus cereus sensu lato, a group with low genetic diversity but produces several promising antimicrobial compounds. B. thuringiensis DNG9, isolated from an oil-contaminated slough in Algeria, has strong antibacterial, antifungal and biosurfactant properties. Here, we report the 6.06 Mbp draft genome sequence of B. thuringiensis DNG9. The genome encodes several gene inventories for the biosynthesis of bioactive compounds such as zwittermycin A, petrobactin, insecticidal toxins, polyhydroxyalkanoates and multiple bacteriocins. We expect the genome information of strain DNG9 will provide another model system to study pathogenicity against insect pests, plant diseases, and antimicrobial compound mining and comparative phylogenesis among the Bacillus cereus sensu lato group.}, } @article {pmid30344640, year = {2018}, author = {Macková, L and Vít, P and Urfus, T}, title = {Crop-to-wild hybridization in cherries-Empirical evidence from Prunus fruticosa.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1748-1759}, pmid = {30344640}, issn = {1752-4571}, abstract = {Crop cultivation can lead to genetic swamping of indigenous species and thus pose a serious threat for biodiversity. The rare Eurasian tetraploid shrub Prunus fruticosa (ground cherry) is suspected of hybridizing with cultivated allochthonous tetraploid P. cerasus and autochthonous diploid P. avium. Three Prunus taxa (447 individuals of P. fruticosa, 43 of P. cerasus and 73 of P. avium) and their hybrids (198 individuals) were evaluated using analysis of absolute genome size/ploidy level and multivariate morphometrics. Flow cytometry revealed considerable differentiation in absolute genome size at the tetraploid level (average 2C of P. fruticosa = 1.30 pg, average 2C of P. cerasus = 1.42 pg, i.e., a 9.2% difference). The combination of methods used allowed us to ascertain the frequency of hybrids occurring under natural conditions in Central Europe. The morphological evaluation of leaves was based upon distance-based morphometrics supplemented by elliptic Fourier analysis. The results provided substantial evidence for ongoing hybridization (hybrids occurred in 39.5% of P. fruticosa populations). We detected homoploid introgressive hybridization with alien P. cerasus at the tetraploid level. We also found previously overlooked but frequent triploid hybrids resulting from heteroploid hybridization with indigenous P. avium, which, however, probably represent only the F1 generation. Although both hybrids differ in ploidy, they cannot be distinguished using morphometrics. Hybrids are frequent and may endanger wild populations of genuine P. fruticosa via direct niche competition or, alternatively or in addition, via introgression at the homoploid level (i.e., genetic swamping). The cultivation of cherries thus substantially threatens the existence of genuine P. fruticosa.}, } @article {pmid30344639, year = {2018}, author = {Hoey, JA and Pinsky, ML}, title = {Genomic signatures of environmental selection despite near-panmixia in summer flounder.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1732-1747}, pmid = {30344639}, issn = {1752-4571}, abstract = {Rapid environmental change is altering the selective pressures experienced by marine species. While adaptation to local environmental conditions depends on a balance between dispersal and natural selection across the seascape, the spatial scale of adaptation and the relative importance of mechanisms maintaining adaptation in the ocean are not well understood. Here, using population assignment tests, Approximate Bayesian Computation (ABC), and genome scans with double-digest restriction-site associated DNA sequencing data, we evaluated population structure and locus-environment associations in a commercially important species, summer flounder (Paralichthys dentatus), along the U.S. east coast. Based on 1,137 single nucleotide polymorphisms across 232 individuals spanning nearly 1,900 km, we found no indication of population structure across Cape Hatteras, North Carolina (FST = 0.0014) or of isolation by distance along the coast using individual relatedness. ABC estimated the probability of dispersal across the biogeographic break at Cape Hatteras to be high (95% credible interval: 7%-50% migration). However, we found 15 loci whose allele frequencies were associated with at least one of four environmental variables. Of those, 11 were correlated with bottom temperature. For summer flounder, our results suggest continued fisheries management as a single population and identify likely response mechanisms to climate change. Broadly speaking, our findings suggest that spatial balancing selection can manifest in adaptive divergence on regional scales in marine fish despite high dispersal, and that these conditions likely result in the widespread distribution of adaptive alleles and a high potential for future genetic adaptation in response to changing environmental conditions. In the context of a rapidly changing world, a landscape genomics perspective offers a useful approach for understanding the causes and consequences of genetic differentiation.}, } @article {pmid30344638, year = {2018}, author = {Summers, JL and Bernik, B and Saunders, CJ and McLachlan, JS and Blum, MJ}, title = {A century of genetic variation inferred from a persistent soil-stored seed bank.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1715-1731}, pmid = {30344638}, issn = {1752-4571}, abstract = {Stratigraphic accretion of dormant propagules in soil can result in natural archives useful for studying ecological and evolutionary responses to environmental change. Few attempts have been made, however, to use soil-stored seed banks as natural archives, in part because of concerns over nonrandom attrition and mixed stratification. Here, we examine the persistent seed bank of Schoenoplectus americanus, a foundational brackish marsh sedge, to determine whether it can serve as a resource for reconstructing historical records of demographic and population genetic variation. After assembling profiles of the seed bank from radionuclide-dated soil cores, we germinated seeds to "resurrect" cohorts spanning the 20th century. Using microsatellite markers, we assessed genetic diversity and differentiation among depth cohorts, drawing comparisons to extant plants at the study site and in nearby and more distant marshes. We found that seed density peaked at intermediate soil depths. We also detected genotypic differences among cohorts as well as between cohorts and extant plants. Genetic diversity did not decline with depth, indicating that the observed pattern of differentiation is not due to attrition. Patterns of differentiation within and among extant marshes also suggest that local populations persist as aggregates of small clones, likely reflecting repeated seedling recruitment and low immigration from admixed regional gene pools. These findings indicate that persistent and stratified soil-stored seed banks merit further consideration as resources for reconstructing decadal- to century-long records that can lend insight into the tempo and nature of ecological and evolutionary processes that shape populations over time.}, } @article {pmid30344637, year = {2018}, author = {Ashrafi, R and Bruneaux, M and Sundberg, LR and Pulkkinen, K and Valkonen, J and Ketola, T}, title = {Broad thermal tolerance is negatively correlated with virulence in an opportunistic bacterial pathogen.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1700-1714}, pmid = {30344637}, issn = {1752-4571}, abstract = {Predicting the effects of global increase in temperatures on disease virulence is challenging, especially for environmental opportunistic bacteria, because pathogen fitness may be differentially affected by temperature within and outside host environment. So far, there is very little empirical evidence on the connections between optimal temperature range and virulence in environmentally growing pathogens. Here, we explored whether the virulence of an environmentally growing opportunistic fish pathogen, Flavobacterium columnare, is malleable to evolutionary changes via correlated selection on thermal tolerance. To this end, we experimentally quantified the thermal performance curves (TPCs) for maximum biomass yield of 49 F. columnare isolates from eight different geographic locations in Finland over ten years (2003-2012). We also characterized virulence profiles of these strains in a zebra fish (Danio rerio) infection model. We show that virulence among the strains increased over the years, but thermal generalism, and in particular tolerance to higher temperatures, was negatively associated with virulence. Our data suggest that temperature has a strong effect on the pathogen genetic diversity and therefore presumably also on disease dynamics. However, the observed increase in frequency and severity of F. columnare epidemics over the last decade cannot be directly linked to bacterial evolution due to increased mean temperature, but is most likely associated with factors related to increased length of growing season, or other time-dependent change in environment. Our study demonstrates that complex interactions between the host, the pathogen and the environment influence disease virulence of an environmentally growing opportunistic pathogen.}, } @article {pmid30344636, year = {2018}, author = {Chen, Z and Farrell, AP and Matala, A and Hoffman, N and Narum, SR}, title = {Physiological and genomic signatures of evolutionary thermal adaptation in redband trout from extreme climates.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1686-1699}, pmid = {30344636}, issn = {1752-4571}, abstract = {Temperature is a master environmental factor that limits the geographical distribution of species, especially in ectotherms. To address challenges in biodiversity conservation under ongoing climate change, it is essential to characterize relevant functional limitations and adaptive genomic content at population and species levels. Here, we present evidence for adaptive divergence in cardiac function and genomic regions in redband trout (Oncorhynchus mykiss gairdneri) populations from desert and montane streams. Cardiac phenotypes of individual fish were measured in the field with a custom-built electrocardiogram apparatus. Maximum heart rate and its rate limiting temperature during acute warming were significantly higher in fish that have evolved in the extreme of a desert climate compared to a montane climate. Association mapping with 526,301 single nucleotide polymorphisms (SNPs) across the genome revealed signatures of thermal selection both within and among ecotypes. Among desert and montane populations, 435 SNPs were identified as putative outliers under natural selection and 20 of these loci showed significant association with average summer water temperatures among populations. Phenotypes for cardiac performance were variable within each ecotype, and 207 genomic regions were strongly associated with either maximum heart rate or rate limiting temperatures among individuals. Annotation of significant loci provided candidate genes that underlie thermal adaptation, including pathways associated with cardiac function (IRX5, CASQ1, CAC1D, and TITIN), neuroendocrine system (GPR17 and NOS), and stress response (SERPH). By integrating comparative physiology and population genomics, results here advance our knowledge on evolutionary processes of thermal adaptation in aquatic ectotherms.}, } @article {pmid30344635, year = {2018}, author = {Lavoie, C and Courcelle, M and Redivo, B and Derome, N}, title = {Structural and compositional mismatch between captive and wild Atlantic salmon (Salmo salar) parrs' gut microbiota highlights the relevance of integrating molecular ecology for management and conservation methods.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1671-1685}, pmid = {30344635}, issn = {1752-4571}, abstract = {Stocking methods are used in the Province of Quebec to restore Salmo salar populations. However, Atlantic salmon stocked juveniles show higher mortality rates than wild ones when introduced into nature. Hatchery environment, which greatly differs from the natural environment, is identified as the main driver of the phenotypic mismatch between captive and wild parrs. The latter is also suspected to impact the gut microbiota composition, which can be associated with essential metabolic functions for their host. We hypothesized that hatchery-raised parrs potentially recruit gut microbial communities that are different from those recruited in the wild. This study evaluated the impacts of artificial rearing on gut microbiota composition in 0+ parrs meant for stocking in two distinct Canadian rivers: Rimouski and Malbaie (Quebec, Canada). Striking differences between hatchery and wild-born parrs' gut microbiota suggest that microbiota could be another factor that could impact their survival in the targeted river, because the microbiome is narrowly related to host physiology. For instance, major commensals belonging to Enterobacteriaceae and Clostridiacea from wild parrs' gut microbiota were substituted in captive parrs by lactic acid bacteria from the Lactobacillaceae family. Overall, captive parrs host a generalist bacterial community whereas wild parrs' microbiota is much more specialized. This is the very first study demonstrating extensive impact of captive rearing on intestinal microbiota composition in Atlantic salmon intended for wild population stocking. Our results strongly suggest the need to implement microbial ecology concepts into conservation management of endangered salmon stocks supplemented with hatchery-reared parrs.}, } @article {pmid30344634, year = {2018}, author = {Lehnert, SJ and DiBacco, C and Jeffery, NW and Blakeslee, AMH and Isaksson, J and Roman, J and Wringe, BF and Stanley, RRE and Matheson, K and McKenzie, CH and Hamilton, LC and Bradbury, IR}, title = {Temporal dynamics of genetic clines of invasive European green crab (Carcinus maenas) in eastern North America.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1656-1670}, pmid = {30344634}, issn = {1752-4571}, abstract = {Two genetically distinct lineages of European green crabs (Carcinus maenas) were independently introduced to eastern North America, the first in the early 19th century and the second in the late 20th century. These lineages first came into secondary contact in southeastern Nova Scotia, Canada (NS), where they hybridized, producing latitudinal genetic clines. Previous studies have documented a persistent southward shift in the clines of different marker types, consistent with existing dispersal and recruitment pathways. We evaluated current clinal structure by quantifying the distribution of lineages and fine-scale hybridization patterns across the eastern North American range (25 locations, ~39 to 49°N) using informative single nucleotide polymorphisms (SNPs; n = 96). In addition, temporal changes in the genetic clines were evaluated using mitochondrial DNA and microsatellite loci (n = 9-11) over a 15-year period (2000-2015). Clinal structure was consistent with prior work demonstrating the existence of both northern and southern lineages with a hybrid zone occurring between southern New Brunswick (NB) and southern NS. Extensive later generation hybrids were detected in this region and in southeastern Newfoundland. Temporal genetic analysis confirmed the southward progression of clines over time; however, the rate of this progression was slower than predicted by forecasting models, and current clines for all marker types deviated significantly from these predictions. Our results suggest that neutral and selective processes contribute to cline dynamics, and ultimately, highlight how selection, hybridization, and dispersal can collectively influence invasion success.}, } @article {pmid30344633, year = {2018}, author = {Silva, NM and Rio, J and Kreutzer, S and Papageorgopoulou, C and Currat, M}, title = {Bayesian estimation of partial population continuity using ancient DNA and spatially explicit simulations.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1642-1655}, pmid = {30344633}, issn = {1752-4571}, abstract = {The retrieval of ancient DNA from osteological material provides direct evidence of human genetic diversity in the past. Ancient DNA samples are often used to investigate whether there was population continuity in the settlement history of an area. Methods based on the serial coalescent algorithm have been developed to test whether the population continuity hypothesis can be statistically rejected by analysing DNA samples from the same region but of different ages. Rejection of this hypothesis is indicative of a large genetic shift, possibly due to immigration occurring between two sampling times. However, this approach is only able to reject a model of full continuity model (a total absence of genetic input from outside), but admixture between local and immigrant populations may lead to partial continuity. We have recently developed a method to test for population continuity that explicitly considers the spatial and temporal dynamics of populations. Here, we extended this approach to estimate the proportion of genetic continuity between two populations, using ancient genetic samples. We applied our original approach to the question of the Neolithic transition in Central Europe. Our results confirmed the rejection of full continuity, but our approach represents an important step forward by estimating the relative contribution of immigrant farmers and of local hunter-gatherers to the final Central European Neolithic genetic pool. Furthermore, we show that a substantial proportion of genes brought by the farmers in this region were assimilated from other hunter-gatherer populations along the way from Anatolia, which was not detectable by previous continuity tests. Our approach is also able to jointly estimate demographic parameters, as we show here by finding both low density and low migration rate for pre-Neolithic hunter-gatherers. It provides a useful tool for the analysis of the numerous ancient DNA data sets that are currently being produced for many different species.}, } @article {pmid30344632, year = {2018}, author = {Moulton-Brown, CE and Friman, VP}, title = {Rapid evolution of generalized resistance mechanisms can constrain the efficacy of phage-antibiotic treatments.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1630-1641}, pmid = {30344632}, issn = {1752-4571}, abstract = {Antimicrobial resistance has been estimated to be responsible for over 700,000 deaths per year; therefore, new antimicrobial therapies are urgently needed. One way to increase the efficiency of antibiotics is to use them in combination with bacteria-specific parasitic viruses, phages, which have been shown to exert additive or synergistic effects in controlling bacteria. However, it is still unclear to what extent these combinatory effects are limited by rapid evolution of resistance, especially when the pathogen grows as biofilm on surfaces typical for many persistent and chronic infections. To study this, we used a microcosm system, where genetically isogenic populations of Pseudomonas aeruginosa PAO1 bacterial pathogen were exposed to a phage 14/1, gentamycin or a combination of them both in a spatially structured environment. We found that even though antibiotic and phage-antibiotic treatments were equally effective at controlling bacteria in the beginning of the experiment, combination treatment rapidly lost its efficacy in both planktonic and biofilm populations. In a mechanistic manner, this was due to rapid resistance evolution: While both antibiotic and phage selected for increased resistance on their own, phage selection correlated positively with increase in antibiotic resistance, while biofilm growth, which provided generalized resistance mechanism, was favoured most in the combination treatment. Only relatively small cost of resistance and weak evidence for coevolutionary dynamics were observed. Together, these results suggest that spatial heterogeneity can promote rapid evolution of generalized resistance mechanisms without corresponding increase in phage infectivity, which could potentially limit the effectiveness of phage-antibiotic treatments in the evolutionary timescale.}, } @article {pmid30344631, year = {2018}, author = {Diedericks, G and Henriques, R and von der Heyden, S and Weyl, OLF and Hui, C}, title = {The ghost of introduction past: Spatial and temporal variability in the genetic diversity of invasive smallmouth bass.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1609-1629}, pmid = {30344631}, issn = {1752-4571}, abstract = {Understanding the demographic history of introduced populations is essential for unravelling their invasive potential and adaptability to a novel environment. To this end, levels of genetic diversity within the native and invasive range of a species are often compared. Most studies, however, focus solely on contemporary samples, relying heavily on the premise that the historic population structure within the native range has been maintained over time. Here, we assess this assumption by conducting a three-way comparison of the genetic diversity of native (historic and contemporary) and invasive (contemporary) smallmouth bass (Micropterus dolomieu) populations. Analyses of a total of 572 M. dolomieu samples, representing the contemporary invasive South African range, contemporary and historical native USA range (dating back to the 1930s when these fish were first introduced into South Africa), revealed that the historical native range had higher genetic diversity levels when compared to both contemporary native and invasive ranges. These results suggest that both contemporary populations experienced a recent genetic bottleneck. Furthermore, the invasive range displayed significant population structure, whereas both historical and contemporary native US populations revealed higher levels of admixture. Comparison of contemporary and historical samples showed both a historic introduction of M. dolomieu and a more recent introduction, thereby demonstrating that undocumented introductions of this species have occurred. Although multiple introductions might have contributed to the high levels of genetic diversity in the invaded range, we discuss alternative factors that may have been responsible for the elevated levels of genetic diversity and highlight the importance of incorporating historic specimens into demographic analyses.}, } @article {pmid30344630, year = {2018}, author = {Tang, Q and Low, GW and Lim, JY and Gwee, CY and Rheindt, FE}, title = {Human activities and landscape features interact to closely define the distribution and dispersal of an urban commensal.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1598-1608}, pmid = {30344630}, issn = {1752-4571}, abstract = {The rock pigeon, Columba livia, is a cosmopolitan human commensal, domesticated thousands of years ago. However, the human-mediated factors governing its distribution and dispersal are not well understood. In this study, we performed (a) hierarchical distance sampling on ~400 island-wide point transects, (b) a population genomic inquiry based on ~7,000 SNPs from almost 150 individuals, and (c) landscape genomic analyses on the basis of extensive ecological and socio-economic databases to characterize the distribution and dispersal patterns of rock pigeons across Singapore. Our distance sampling results indicated that the volume of intentional "mercy feeding" and availability of high-rise buildings are the most reliable predictors of high pigeon densities in Singapore. Genomic analyses demonstrated that rock pigeons in Singapore form a single population possibly derived from rapid expansion from a genetically homogenous group of founder individuals. In specific, rock pigeons in Singapore lack sex-biased dispersal and are clustered with a genetic patch size of ~3 km. Landscape genomic analyses of great precision pointed to the presence of dense trees as agents of resistance to dispersal, whereas a high road density reduces this resistance. By pinpointing a range of ecological and socio-economic variables determining the distribution and dispersal of pigeons, our study provides urban planners with the tools for optimal management of this human commensal, such as a curtailment of the practice of mercy feeding and modifications to the urban landscape to reduce pigeon density and to lower the likelihood of repopulation by dispersal.}, } @article {pmid30344629, year = {2018}, author = {Guzinski, J and Ballenghien, M and Daguin-Thiébaut, C and Lévêque, L and Viard, F}, title = {Population genomics of the introduced and cultivated Pacific kelp Undaria pinnatifida: Marinas-not farms-drive regional connectivity and establishment in natural rocky reefs.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1582-1597}, pmid = {30344629}, issn = {1752-4571}, abstract = {Ports and farms are well-known primary introduction hot spots for marine non-indigenous species (NIS). The extent to which these anthropogenic habitats are sustainable sources of propagules and influence the evolution of NIS in natural habitats was examined in the edible seaweed Undaria pinnatifida, native to Asia and introduced to Europe in the 1970s. Following its deliberate introduction 40 years ago along the French coast of the English Channel, this kelp is now found in three contrasting habitat types: farms, marinas and natural rocky reefs. In the light of the continuous spread of this NIS, it is imperative to better understand the processes behind its sustainable establishment in the wild. In addition, developing effective management plans to curtail the spread of U. pinnatifida requires determining how the three types of populations interact with one another. In addition to an analysis using microsatellite markers, we developed, for the first time in a kelp, a ddRAD-sequencing technique to genotype 738 individuals sampled in 11 rocky reefs, 12 marinas, and two farms located along ca. 1,000 km of coastline. As expected, the RAD-seq panel showed more power than the microsatellite panel for identifying fine-grained patterns. However, both panels demonstrated habitat-specific properties of the study populations. In particular, farms displayed very low genetic diversity and no inbreeding conversely to populations in marinas and natural rocky reefs. In addition, strong, but chaotic regional genetic structure, was revealed, consistent with human-mediated dispersal (e.g., leisure boating). We also uncovered a tight relationship between populations in rocky reefs and those in nearby marinas, but not with nearby farms, suggesting spillover from marinas into the wild. At last, a temporal survey spanning 20 generations showed that wild populations are now self-sustaining, albeit there was no evidence for local adaptation to any of the three habitats. These findings highlight that limiting the spread of U. pinnatifida requires efficient management policies that also target marinas.}, } @article {pmid30344628, year = {2018}, author = {White, SL and Miller, WL and Dowell, SA and Bartron, ML and Wagner, T}, title = {Limited hatchery introgression into wild brook trout (Salvelinus fontinalis) populations despite reoccurring stocking.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1567-1581}, pmid = {30344628}, issn = {1752-4571}, abstract = {Due to increased anthropogenic pressures on many fish populations, supplementing wild populations with captive-raised individuals has become an increasingly common management practice. Stocking programs can be controversial due to uncertainty about the long-term fitness effects of genetic introgression on wild populations. In particular, introgression between hatchery and wild individuals can cause declines in wild population fitness, resiliency, and adaptive potential and contribute to local population extirpation. However, low survival and fitness of captive-raised individuals can minimize the long-term genetic consequences of stocking in wild populations, and to date the prevalence of introgression in actively stocked ecosystems has not been rigorously evaluated. We quantified the extent of introgression in 30 populations of wild brook trout (Salvelinus fontinalis) in a Pennsylvania watershed and examined the correlation between introgression and 11 environmental covariates. Genetic assignment tests were used to determine the origin (wild vs. captive-raised) for 1,742 wild-caught and 300 hatchery brook trout. To avoid assignment biases, individuals were assigned to two simulated populations that represented the average allele frequencies in wild and hatchery groups. Fish with intermediate probabilities of wild ancestry were classified as introgressed, with threshold values determined through simulation. Even with reoccurring stocking at most sites, over 93% of wild-caught individuals probabilistically assigned to wild origin, and only 5.6% of wild-caught fish assigned to introgressed. Models examining environmental drivers of introgression explained <3% of the among-population variability, and all estimated effects were highly uncertain. This was not surprising given overall low introgression observed in this study. Our results suggest that introgression of hatchery-derived genotypes can occur at low rates, even in actively stocked ecosystems and across a range of habitats. However, a cautious approach to stocking may still be warranted, as the potential effects of stocking on wild population fitness and the mechanisms limiting introgression are not known.}, } @article {pmid30344627, year = {2018}, author = {Littrell, KA and Ellis, D and Gephard, SR and MacDonald, AD and Palkovacs, EP and Scranton, K and Post, DM}, title = {Evaluating the potential for prezygotic isolation and hybridization between landlocked and anadromous alewife (Alosa pseudoharengus) following secondary contact.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1554-1566}, pmid = {30344627}, issn = {1752-4571}, abstract = {The recent increase in river restoration projects is altering habitat connectivity for many aquatic species, increasing the chance that previously isolated populations will come into secondary contact. Anadromous and landlocked alewife (Alosa pseudoharengus) are currently undergoing secondary contact as a result of a fishway installation at Rogers Lake in Old Lyme, Connecticut. To determine the degree of prezygotic isolation and potential for hybridization between alewife life history forms, we constructed spawning time distributions for two anadromous and three landlocked alewife populations using otolith-derived age estimates. In addition, we analyzed long-term data from anadromous alewife migratory spawning runs to look for trends in arrival date and spawning time. Our results indicated that anadromous alewife spawned earlier and over a shorter duration than landlocked alewife, but 3%-13% of landlocked alewife spawning overlapped with the anadromous alewife spawning period. The degree of spawning time overlap was primarily driven by annual and population-level variation in the timing of spawning by landlocked alewife, whereas the timing and duration of spawning for anadromous alewife were found to be relatively invariant among years in our study system. For alewife and many other anadromous fish species, the increase in fish passage river restoration projects in the coming decades will re-establish habitat connectivity and may bring isolated populations into contact. Hybridization between life history forms may occur when prezygotic isolating mechanisms are minimal, leading to potentially rapid ecological and evolutionary changes in restored habitats.}, } @article {pmid30344626, year = {2018}, author = {Bajda, S and Riga, M and Wybouw, N and Papadaki, S and Ouranou, E and Fotoukkiaii, SM and Vontas, J and Van Leeuwen, T}, title = {Fitness costs of key point mutations that underlie acaricide target-site resistance in the two-spotted spider mite Tetranychus urticae.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1540-1553}, pmid = {30344626}, issn = {1752-4571}, abstract = {The frequency of insecticide/acaricide target-site resistance is increasing in arthropod pest populations and is typically underpinned by single point mutations that affect the binding strength between the insecticide/acaricide and its target-site. Theory predicts that although resistance mutations clearly have advantageous effects under the selection pressure of the insecticide/acaricide, they might convey negative pleiotropic effects on other aspects of fitness. If such fitness costs are in place, target-site resistance is thus likely to disappear in the absence of insecticide/acaricide treatment, a process that would counteract the spread of resistance in agricultural crops. Hence, there is a great need to reliably quantify the various potential pleiotropic effects of target-site resistance point mutations on arthropod fitness. Here, we used near-isogenic lines of the spider mite pest Tetranychus urticae that carry well-characterized acaricide target-site resistance mutations to quantify potential fitness costs. Specifically, we analyzed P262T in the mitochondrial cytochrome b, the combined G314D and G326E substitutions in the glutamate-gated chloride channels, L1024V in the voltage-gated sodium channel, and I1017F in chitin synthase 1. Five fertility life table parameters and nine single-generation life-history traits were quantified and compared across a total of 15 mite lines. In addition, we monitored the temporal resistance level dynamics of populations with different starting frequency levels of the chitin synthase resistant allele to further support our findings. Three target-site resistance mutations, I1017F and the co-occurring G314D and G326E mutations, were shown to significantly and consistently alter certain fitness parameters in T. urticae. The other two mutations (P262T and L1024V) did not result in any consistent change in a fitness parameter analyzed in our study. Our findings are discussed in the context of the global spread of T. urticae pesticide resistance and integrated pest management.}, } @article {pmid30344625, year = {2018}, author = {Knutsen, H and Jorde, PE and Hutchings, JA and Hemmer-Hansen, J and Grønkjær, P and Jørgensen, KM and André, C and Sodeland, M and Albretsen, J and Olsen, EM}, title = {Stable coexistence of genetically divergent Atlantic cod ecotypes at multiple spatial scales.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1527-1539}, pmid = {30344625}, issn = {1752-4571}, abstract = {Coexistence in the same habitat of closely related yet genetically different populations is a phenomenon that challenges our understanding of local population structure and adaptation. Identifying the underlying mechanisms for such coexistence can yield new insight into adaptive evolution, diversification and the potential for organisms to adapt and persist in response to a changing environment. Recent studies have documented cryptic, sympatric populations of Atlantic cod (Gadus morhua) in coastal areas. We analysed genetic origin of 6,483 individual cod sampled annually over 14 years from 125 locations along the Norwegian Skagerrak coast and document stable coexistence of two genetically divergent Atlantic cod ecotypes throughout the study area and study period. A "fjord" ecotype dominated in numbers deep inside fjords while a "North Sea" ecotype was the only type found in offshore North Sea. Both ecotypes coexisted in similar proportions throughout coastal habitats at all spatial scales. The size-at-age of the North Sea ecotype on average exceeded that of the fjord ecotype by 20% in length and 80% in weight across all habitats. Different growth and size among individuals of the two types might be one of several ecologically significant variables that allow for stable coexistence of closely related populations within the same habitat. Management plans, biodiversity initiatives and other mitigation strategies that do not account for the mixture of species ecotypes are unlikely to meet objectives related to the sustainability of fish and fisheries.}, } @article {pmid30344624, year = {2018}, author = {Waples, RS and Lindley, ST}, title = {Genomics and conservation units: The genetic basis of adult migration timing in Pacific salmonids.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1518-1526}, pmid = {30344624}, issn = {1752-4571}, abstract = {It is now routinely possible to generate genomics-scale datasets for nonmodel species; however, many questions remain about how best to use these data for conservation and management. Some recent genomics studies of anadromous Pacific salmonids have reported a strong association between alleles at one or a very few genes and a key life history trait (adult migration timing) that has played an important role in defining conservation units. Publication of these results has already spurred a legal challenge to the existing framework for managing these species, which was developed under the paradigm that most phenotypic traits are controlled by many genes of small effect, and that parallel evolution of life history traits is common. But what if a key life history trait can only be expressed if a specific allele is present? Does the current framework need to be modified to account for the new genomics results, as some now propose? Although this real-world example focuses on Pacific salmonids, the issues regarding how genomics can inform us about the genetic basis of phenotypic traits, and what that means for applied conservation, are much more general. In this perspective, we consider these issues and outline a general process that can be used to help generate the types of additional information that would be needed to make informed decisions about the adequacy of existing conservation and management frameworks.}, } @article {pmid30344623, year = {2018}, author = {Valkonen, JK and Mäkelä, A and Mappes, J and López-Sepulcre, A}, title = {Evaluating the potential for evolutionary mismatch in Batesian mimics: A case study in the endangered smooth snake (Coronella austriaca).}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1512-1517}, pmid = {30344623}, issn = {1752-4571}, abstract = {Many harmless organisms gain a survival advantage by mimicking venomous species. This is the case of the endangered smooth snake (Coronella austriaca), which mimics venomous vipers. Although this may protect the smooth snake against most of its natural predators, it may render them at greater risk of mortality from humans, who are more inclined to kill species, such as vipers, that they consider dangerous. This may cause an evolutionary mismatch, whereby humans may counteract the natural advantage of mimicry. We explore this possibility of evaluating the willingness of humans to kill smooth snakes versus the adder (Vipera berus), as well as their ability to discern them in the Åland Islands. Our results show that, even when respondents did not wish to kill the smooth snakes, these were often mistaken for adders, which they were willing to kill. Altogether, viper mimicry brought about a 2.3-fold increase in the likelihood of smooth snakes being killed upon human encounter. These results open up the possibility that naturally selected mimicry can pose a threat to endangered snakes in human-influenced habitats. We discuss the potential for this to be the case, and highlight the importance of protecting entire mimicry complexes, rather than single species, when the endangered species is a mimic.}, } @article {pmid30344622, year = {2018}, author = {Nguyen, QH and Contamin, L and Nguyen, TVA and Bañuls, AL}, title = {Insights into the processes that drive the evolution of drug resistance in Mycobacterium tuberculosis.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1498-1511}, pmid = {30344622}, issn = {1752-4571}, abstract = {At present, the successful transmission of drug-resistant Mycobacterium tuberculosis, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) strains, in human populations, threatens tuberculosis control worldwide. Differently from many other bacteria, M. tuberculosis drug resistance is acquired mainly through mutations in specific drug resistance-associated genes. The panel of mutations is highly diverse, but depends on the affected gene and M. tuberculosis genetic background. The variety of genetic profiles observed in drug-resistant clinical isolates underlines different evolutionary trajectories towards multiple drug resistance, although some mutation patterns are prominent. This review discusses the intrinsic processes that may influence drug resistance evolution in M. tuberculosis, such as mutation rate, drug resistance-associated mutations, fitness cost, compensatory mutations and epistasis. This knowledge should help to better predict the risk of emergence of highly resistant M. tuberculosis strains and to develop new tools and strategies to limit the development and spread of MDR and XDR strains.}, } @article {pmid30344621, year = {2018}, author = {Kruitwagen, A and Beukeboom, LW and Wertheim, B}, title = {Optimization of native biocontrol agents, with parasitoids of the invasive pest Drosophila suzukii as an example.}, journal = {Evolutionary applications}, volume = {11}, number = {9}, pages = {1473-1497}, pmid = {30344621}, issn = {1752-4571}, abstract = {The development of biological control methods for exotic invasive pest species has become more challenging during the last decade. Compared to indigenous natural enemies, species from the pest area of origin are often more efficient due to their long coevolutionary history with the pest. The import of these well-adapted exotic species, however, has become restricted under the Nagoya Protocol on Access and Benefit Sharing, reducing the number of available biocontrol candidates. Finding new agents and ways to improve important traits for control agents ("biocontrol traits") is therefore of crucial importance. Here, we demonstrate the potential of a surprisingly under-rated method for improvement of biocontrol: the exploitation of intraspecific variation in biocontrol traits, for example, by selective breeding. We propose a four-step approach to investigate the potential of this method: investigation of the amount of (a) inter- and (b) intraspecific variation for biocontrol traits, (c) determination of the environmental and genetic factors shaping this variation, and (d) exploitation of this variation in breeding programs. We illustrate this approach with a case study on parasitoids of Drosophila suzukii, a highly invasive pest species in Europe and North America. We review all known parasitoids of D. suzukii and find large variation among and within species in their ability to kill this fly. We then consider which genetic and environmental factors shape the interaction between D. suzukii and its parasitoids to explain this variation. Insight into the causes of variation informs us on how and to what extent candidate agents can be improved. Moreover, it aids in predicting the effectiveness of the agent upon release and provides insight into the selective forces that are limiting the adaptation of indigenous species to the new pest. We use this knowledge to give future research directions for the development of selective breeding methods for biocontrol agents.}, } @article {pmid30343986, year = {2018}, author = {Dantas-Torres, F}, title = {Species Concepts: What about Ticks?.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1017-1026}, doi = {10.1016/j.pt.2018.09.009}, pmid = {30343986}, issn = {1471-5007}, abstract = {Since ancient times, philosophers and taxonomists have tried to classify forms of life. This is what taxonomy is about: the science of identifying, naming, classifying, and describing organisms. In this article I address the issue of the species concept in tick taxonomy. While the typological species concept is still the most widely used, the biological and phylogenetic species concepts are growing in popularity among tick taxonomists. The integrative approach is increasingly being used, but the question is how to define a tick species when using this approach, particularly if data are incongruent. The adoption of an integrative species concept is discussed, in light of recent advances in our understanding of the genetics, morphology, and biology of ticks.}, } @article {pmid30343674, year = {2018}, author = {Sims, S and Longmire, AG and Campo, DS and Ramachandran, S and Medrzycki, M and Ganova-Raeva, L and Lin, Y and Sue, A and Thai, H and Zelikovsky, A and Khudyakov, Y}, title = {Automated quality control for a molecular surveillance system.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 11}, pages = {358}, pmid = {30343674}, issn = {1471-2105}, mesh = {Automation ; Disease Outbreaks/*prevention & control ; Genotyping Techniques ; Hepacivirus/physiology ; Hepatitis C/epidemiology/virology ; Humans ; Population Surveillance/*methods ; Quality Control ; Reference Standards ; United States ; }, abstract = {BACKGROUND: Molecular surveillance and outbreak investigation are important for elimination of hepatitis C virus (HCV) infection in the United States. A web-based system, Global Hepatitis Outbreak and Surveillance Technology (GHOST), has been developed using Illumina MiSeq-based amplicon sequence data derived from the HCV E1/E2-junction genomic region to enable public health institutions to conduct cost-effective and accurate molecular surveillance, outbreak detection and strain characterization. However, as there are many factors that could impact input data quality to which the GHOST system is not completely immune, accuracy of epidemiological inferences generated by GHOST may be affected. Here, we analyze the data submitted to the GHOST system during its pilot phase to assess the nature of the data and to identify common quality concerns that can be detected and corrected automatically.

RESULTS: The GHOST quality control filters were individually examined, and quality failure rates were measured for all samples, including negative controls. New filters were developed and introduced to detect primer dimers, loss of specimen-specific product, or short products. The genotyping tool was adjusted to improve the accuracy of subtype calls. The identification of "chordless" cycles in a transmission network from data generated with known laboratory-based quality concerns allowed for further improvement of transmission detection by GHOST in surveillance settings. Parameters derived to detect actionable common quality control anomalies were incorporated into the automatic quality control module that rejects data depending on the magnitude of a quality problem, and warns and guides users in performing correctional actions. The guiding responses generated by the system are tailored to the GHOST laboratory protocol.

CONCLUSIONS: Several new quality control problems were identified in MiSeq data submitted to GHOST and used to improve protection of the system from erroneous data and users from erroneous inferences. The GHOST system was upgraded to include identification of causes of erroneous data and recommendation of corrective actions to laboratory users.}, } @article {pmid30343671, year = {2018}, author = {Zhao, K and Henderson, E and Bullard, K and Oberste, MS and Burns, CC and Jorba, J}, title = {PoSE: visualization of patterns of sequence evolution using PAML and MATLAB.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 11}, pages = {364}, pmid = {30343671}, issn = {1471-2105}, mesh = {Base Pairing/genetics ; Base Sequence ; Codon/genetics ; *Evolution, Molecular ; Phylogeny ; Poliovirus/genetics ; *Software ; }, abstract = {BACKGROUND: Determining patterns of nucleotide and amino acid substitution is the first step during sequence evolution analysis. However, it is not easy to visualize the different phylogenetic signatures imprinted in aligned nucleotide and amino acid sequences.

RESULTS: Here we present PoSE (Pattern of Sequence Evolution), a reliable resource for unveiling the evolutionary history of sequence alignments and for graphically displaying their contents. Substitutions are displayed by category (transitions and transversions), codon position, and phenotypic effect (synonymous and nonsynonymous). Visualization is accomplished using MATLAB scripts wrapped around PAML (Phylogenetic Analysis by Maximum Likelihood), implemented in an easy-to-use graphical user interface. The application displays inferred substitutions estimated by baseml or codeml, two programs included in the PAML software package. PoSE organizes patterns of substitution in eleven plots, including estimated non-synonymous/synonymous ratios (dN/dS) along the sequence alignment. In addition, PoSE provides visualization and annotation of patterns of amino acid substitutions along groups of related sequences that can be graphically inspected in a phylogenetic tree window.

CONCLUSIONS: PoSE is a useful tool to help determine major patterns during sequence evolution of protein-coding sequences, hypervariable regions, or changes in dN/dS ratios. PoSE is publicly available at https://github.com/CDCgov/PoSE.}, } @article {pmid30343669, year = {2018}, author = {Tsyvina, V and Campo, DS and Sims, S and Zelikovsky, A and Khudyakov, Y and Skums, P}, title = {Fast estimation of genetic relatedness between members of heterogeneous populations of closely related genomic variants.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 11}, pages = {360}, pmid = {30343669}, issn = {1471-2105}, support = {R01 EB025022/EB/NIBIB NIH HHS/United States ; }, mesh = {*Algorithms ; Base Sequence ; Entropy ; *Genetic Variation ; *Genome ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; *Phylogeny ; Reproducibility of Results ; Time Factors ; }, abstract = {BACKGROUND: Many biological analysis tasks require extraction of families of genetically similar sequences from large datasets produced by Next-generation Sequencing (NGS). Such tasks include detection of viral transmissions by analysis of all genetically close pairs of sequences from viral datasets sampled from infected individuals or studying of evolution of viruses or immune repertoires by analysis of network of intra-host viral variants or antibody clonotypes formed by genetically close sequences. The most obvious naïeve algorithms to extract such sequence families are impractical in light of the massive size of modern NGS datasets.

RESULTS: In this paper, we present fast and scalable k-mer-based framework to perform such sequence similarity queries efficiently, which specifically targets data produced by deep sequencing of heterogeneous populations such as viruses. It shows better filtering quality and time performance when comparing to other tools. The tool is freely available for download at https://github.com/vyacheslav-tsivina/signature-sj CONCLUSION: The proposed tool allows for efficient detection of genetic relatedness between genomic samples produced by deep sequencing of heterogeneous populations. It should be especially useful for analysis of relatedness of genomes of viruses with unevenly distributed variable genomic regions, such as HIV and HCV. For the future we envision, that besides applications in molecular epidemiology the tool can also be adapted to immunosequencing and metagenomics data.}, } @article {pmid30343665, year = {2018}, author = {Zare, F and Hosny, A and Nabavi, S}, title = {Noise cancellation using total variation for copy number variation detection.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 11}, pages = {361}, pmid = {30343665}, issn = {1471-2105}, support = {R00 LM011595/LM/NLM NIH HHS/United States ; }, mesh = {Algorithms ; Breast Neoplasms/genetics ; Computer Simulation ; DNA Copy Number Variations/*genetics ; Female ; Genomics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Signal Processing, Computer-Assisted ; Time Factors ; Wavelet Analysis ; }, abstract = {BACKGROUND: Due to recent advances in sequencing technologies, sequence-based analysis has been widely applied to detecting copy number variations (CNVs). There are several techniques for identifying CNVs using next generation sequencing (NGS) data, however methods employing depth of coverage or read depth (RD) have recently become a main technique to identify CNVs. The main assumption of the RD-based CNV detection methods is that the readcount value at a specific genomic location is correlated with the copy number at that location. However, readcount data's noise and biases distort the association between the readcounts and copy numbers. For more accurate CNV identification, these biases and noise need to be mitigated. In this work, to detect CNVs more precisely and efficiently we propose a novel denoising method based on the total variation approach and the Taut String algorithm.

RESULTS: To investigate the performance of the proposed denoising method, we computed sensitivities, false discovery rates and specificities of CNV detection when employing denoising, using both simulated and real data. We also compared the performance of the proposed denoising method, Taut String, with that of the commonly used approaches such as moving average (MA) and discrete wavelet transforms (DWT) in terms of sensitivity of detecting true CNVs and time complexity. The results show that Taut String works better than DWT and MA and has a better power to identify very narrow CNVs. The ability of Taut String denoising in preserving CNV segments' breakpoints and narrow CNVs increases the detection accuracy of segmentation algorithms, resulting in higher sensitivities and lower false discovery rates.

CONCLUSIONS: In this study, we proposed a new denoising method for sequence-based CNV detection based on a signal processing technique. Existing CNV detection algorithms identify many false CNV segments and fail in detecting short CNV segments due to noise and biases. Employing an effective and efficient denoising method can significantly enhance the detection accuracy of the CNV segmentation algorithms. Advanced denoising methods from the signal processing field can be employed to implement such algorithms. We showed that non-linear denoising methods that consider sparsity and piecewise constant characteristics of CNV data result in better performance in CNV detection.}, } @article {pmid30343664, year = {2018}, author = {Pawar, SD and Freas, C and Weber, IT and Harrison, RW}, title = {Analysis of drug resistance in HIV protease.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 11}, pages = {362}, pmid = {30343664}, issn = {1471-2105}, support = {R01 GM062920/GM/NIGMS NIH HHS/United States ; U01 GM062920/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Databases as Topic ; Drug Resistance, Viral/drug effects/*genetics ; Genotype ; HIV Infections/drug therapy ; HIV Protease/*genetics ; HIV Protease Inhibitors/chemistry/pharmacology ; Humans ; Machine Learning ; Principal Component Analysis ; }, abstract = {BACKGROUND: Drug resistance in HIV is the major problem limiting effective antiviral therapy. Computational techniques for predicting drug resistance profiles from genomic data can accelerate the appropriate choice of therapy. These techniques can also be used to select protease mutants for experimental studies of resistance and thereby assist in the development of next-generation therapies.

RESULTS: The machine learning produced highly accurate and robust classification of HIV protease resistance. Genotype data were mapped to the enzyme structure and encoded using Delaunay triangulation. Generative machine learning models trained on one inhibitor could classify resistance from other inhibitors with varying levels of accuracy. Generally, the accuracy was best when the inhibitors were chemically similar.

CONCLUSIONS: Restricted Boltzmann Machines are an effective machine learning tool for classification of genomic and structural data. They can also be used to compare resistance profiles of different protease inhibitors.}, } @article {pmid30343663, year = {2018}, author = {Campbell, F and Didelot, X and Fitzjohn, R and Ferguson, N and Cori, A and Jombart, T}, title = {outbreaker2: a modular platform for outbreak reconstruction.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 11}, pages = {363}, pmid = {30343663}, issn = {1471-2105}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Algorithms ; Biological Evolution ; *Disease Outbreaks ; Ebolavirus/physiology ; Hemorrhagic Fever, Ebola/epidemiology/virology ; Humans ; Markov Chains ; Models, Theoretical ; Monte Carlo Method ; *Software ; }, abstract = {BACKGROUND: Reconstructing individual transmission events in an infectious disease outbreak can provide valuable information and help inform infection control policy. Recent years have seen considerable progress in the development of methodologies for reconstructing transmission chains using both epidemiological and genetic data. However, only a few of these methods have been implemented in software packages, and with little consideration for customisability and interoperability. Users are therefore limited to a small number of alternatives, incompatible tools with fixed functionality, or forced to develop their own algorithms at considerable personal effort.

RESULTS: Here we present outbreaker2, a flexible framework for outbreak reconstruction. This R package re-implements and extends the original model introduced with outbreaker, but most importantly also provides a modular platform allowing users to specify custom models within an optimised inferential framework. As a proof of concept, we implement the within-host evolutionary model introduced with TransPhylo, which is very distinct from the original genetic model in outbreaker, and demonstrate how even complex model results can be successfully included with minimal effort.

CONCLUSIONS: outbreaker2 provides a valuable starting point for future outbreak reconstruction tools, and represents a unifying platform that promotes customisability and interoperability. Implemented in the R software, outbreaker2 joins a growing body of tools for outbreak analysis.}, } @article {pmid30343662, year = {2018}, author = {Camp, B and Mandivarapu, JK and Ramamurthy, N and Wingo, J and Bourgeois, AG and Cao, X and Sunderraman, R}, title = {A new cross-platform architecture for epi-info software suite.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 11}, pages = {359}, pmid = {30343662}, issn = {1471-2105}, mesh = {Databases, Factual ; Disease Outbreaks ; *Epidemiologic Studies ; Humans ; Public Health ; *Software ; User-Computer Interface ; Workflow ; }, abstract = {BACKGROUND: The Epi-Info software suite, built and maintained by the Centers for Disease Control and Prevention (CDC), is widely used by epidemiologists and public health researchers to collect and analyze public health data, especially in the event of outbreaks such as Ebola and Zika. As it exists today, Epi-Info Desktop runs only on the Windows platform, and the larger Epi-Info Suite of products consists of separate codebases for several different devices and use-cases. Software portability has become increasingly important over the past few years as it offers a number of obvious benefits. These include reduced development time, reduced cost, and simplified system architecture. Thus, there is a blatant need for continued research. Specifically, it is critical to fully understand any underlying negative performance issues which arise from platform-agnostic systems. Such understanding should allow for improved design, and thus result in substantial mitigation of reduced performance. In this paper, we present a viable cross-platform architecture for Epi-Info which solves many of these problems.

RESULTS: We have successfully generated executables for Linux, Mac, and Windows from a single code-base, and we have shown that performance need not be completely sacrificed when building a cross-platform application. This has been accomplished by using Electron as a wrapper for an AngularJS app, a Python analytics module, and a local, browser-based NoSQL database.

CONCLUSIONS: Promising results warrant future research. Specifically, the design allows for cross-platform form-design, data-collection, offline/online modes, scalable storage, automatic local-to-remote data sync, and fast analytics which rival more traditional approaches.}, } @article {pmid30343462, year = {2018}, author = {Porokhovnik, LN and Lyapunova, NA}, title = {Dosage effects of human ribosomal genes (rDNA) in health and disease.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9587-y}, pmid = {30343462}, issn = {1573-6849}, abstract = {Human ribosomal RNA genes encoding a pre-transcript of the three major ribosomal RNA (18S, 5.8S, and 28S rRNA) are tandemly repeated in human genome. Their total copy number varies from 250 to 670 per diploid genome with a mean of approximately 420 copies, but only a fraction of them is transcriptionally active. The functional consequences of human ribosomal RNA gene dosage are not widely known and often assumed to be negligible. Here, we review the facts of rRNA gene dosage effects on normal growth and aging, stress resistance of healthy individuals, and survivability of patients with chromosomal abnormalities, as well as on the risk and severity of some multifactorial diseases with proven genetic predisposition. An original hypothesis that rRNA gene dosage can be a modulating factor involved in the pathogenesis of schizophrenia and rheumatoid arthritis is put forward.}, } @article {pmid30343461, year = {2018}, author = {Pradillo, M and Santos, JL}, title = {Genes involved in miRNA biogenesis affect meiosis and fertility.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {4}, pages = {233-241}, doi = {10.1007/s10577-018-9588-x}, pmid = {30343461}, issn = {1573-6849}, support = {AGL2012-38852//Ministerio de Economía y Competitividad/ ; AGL2015-67349-P//Ministerio de Economía y Competitividad/ ; Meiosys-KBBE-2009-222883//FP7 Food, Agriculture and Fisheries, Biotechnology ()/ ; }, abstract = {MicroRNAs (miRNAs) are a class of small (containing about 22 nucleotides) single-stranded non-coding RNAs that regulate gene expression at the post-transcriptional level in plants and animals, being absent from unicellular organisms. They act on diverse key physiological and cellular processes, such as development and tissue differentiation, cell identity, cell cycle progression, and programmed cell death. They are also likely to be involved in a broad spectrum of human diseases. Particularly, this review examines and summarizes work characterizing the function of miRNAs in gametogenesis and fertility. Although numerous studies have elucidated the involvement of reproductive-specific small interfering RNAs (siRNAs) in regulating germ cell development and meiosis, less is known about the role of miRNAs in these processes. We focus on the study of hypomorphic and null alleles of genes encoding components of miRNA biogenesis in both plants (Arabidopsis thaliana) and mammals (Mus musculus). We compare the consequences of the presence of these mutations on male meiosis in both species.}, } @article {pmid30343327, year = {2019}, author = {Chen, X and Liu, J and Xu, Y and Wang, Y and Yan, X}, title = {Erythrobacter nanhaiensis sp. nov., A Novel Member of the Genus Erythrobacter Isolated from the South China Sea.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {57-62}, doi = {10.1007/s00284-018-1584-z}, pmid = {30343327}, issn = {1432-0991}, support = {41606134//NSFC project/ ; 2016YFA0601103//National Key Research and Development Program of China/ ; }, abstract = {A Gram-negative, motile, rod-shaped, aerobic bacterial strain with tufty polar flagella, JLT1363T, was isolated from the South China Sea. The bacteria formed yellow colonies on rich organic medium. The major cellular fatty acids present in JLT1363T were C18:1 ω7c and/or C18:1 ω6c (36.06%), C17:1 ω6c (17.04%), C14:0 2-OH (9.85%), and C16:0 (8.09%). The genome size was ~3.12 Mbps with a G+C content of 64.9%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain JLT1363T fell within the genus Erythrobacter. The 16S rRNA gene sequence similarity between strain JLT1363T and the type strains of Erythrobacter species ranged from 95.0% (with Erythromicrobium ramosum) to 98.7% (with Erythrobacter lutimaris). The Average Nucleotide Identity (ANI) value between genome sequences of strain JLT1363T and Erythrobacter lutimaris KCTC 42109T was 82.2%. Strain JLT1363T lacked bacteriochlorophyll a, and the major polar lipids were sphingoglycolipids, diphosphatidylglycerol, phosphatidylcholine, and phosphatidylglycerol. Phylogenetic and phenotypic properties indicated that strain JLT1363T represents a novel species of the genus Erythrobacter, for which the name Erythrobacter nanhaiensis sp. nov. is proposed. The type strain is JLT1363T (=CGMCC 1.7293T = LMG 24872T).}, } @article {pmid30343326, year = {2019}, author = {Che, L and Xu, W and Zhan, J and Zhang, L and Liu, L and Zhou, H}, title = {Complete Genome Sequence of Bacillus cereus CC-1, A Novel Marine Selenate/Selenite Reducing Bacterium Producing Metallic Selenides Nanomaterials.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {78-85}, doi = {10.1007/s00284-018-1587-9}, pmid = {30343326}, issn = {1432-0991}, support = {31500080//National Natural Science Foundation of China/ ; DUT17JC46//Fundamental Research Funds for the Central Universities/ ; }, abstract = {Metallic selenides nanomaterials are widely used in many fields, especially for photothermal therapy and thermoelectric devices. However, the traditional chemogenic methods are energy-intensive and environmentally unfriendly. In this study, the first complete genome data of a metallic selenides producing bacterium Bacillus cereus CC-1 was reported. This strain can not only reduce selenite and selenate into elemental selenium nanoparticles (SeNPs), but also synthesize several metallic selenides nanoparticles when adding metal ions (Pb2+, Ag+ and Bi3+) and selenite simultaneously. The size of the genome is 5,308,319 bp with 36.07% G+C content. Several putative genes responsible for heavy metal resistance, salt resistance, and selenate reduction were found. This genome data provide fundamental information, which support the use of this strain for the production of biocompatible photothermal and thermoelectric nanomaterials under mild conditions.}, } @article {pmid30343003, year = {2018}, author = {Hwa, T and Sauer, U}, title = {Editorial overview: Current Opinion in Microbiology 2018 Special issue 'Microbial systems biology, vol. 45'.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {vi-viii}, doi = {10.1016/j.mib.2018.09.005}, pmid = {30343003}, issn = {1879-0364}, } @article {pmid30342886, year = {2018}, author = {Eilertsen, M and Valen, R and Drivenes, Ø and Ebbesson, LOE and Helvik, JV}, title = {Transient photoreception in the hindbrain is permissive to the life history transition of hatching in Atlantic halibut.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {129-138}, doi = {10.1016/j.ydbio.2018.10.006}, pmid = {30342886}, issn = {1095-564X}, abstract = {In nonmammalian vertebrates, photoreception takes place in the deep brain already early in development, but knowledge is lacking about the functions of these nonvisual photoreceptive systems. Prior to hatching, Atlantic halibut has a transient bilateral cluster of photoreceptive cells in the hindbrain. The cluster is imbedded in a neuronal network projecting to the narrow belt of hatching glands in the yolk sac. In halibut, hatching is inhibited in light and activated by transfer to darkness and c-fos analysis during hatching shows that the hindbrain cluster and hatching glands have neural activation. Unexpectedly, the hindbrain cluster expresses dual photopigments, vertebrate ancient opsin and melanopsin. Evolutionarily, these opsins are believed to belong to different classes of photopigments found in rhabdomeric and ciliary photoreceptors. The concept that an organism develops transient light sensitivity to target critical aspects of life history transitions as hatching provides a fascinating landscape to investigate the timing of other biological events.}, } @article {pmid30342790, year = {2019}, author = {Hebbring, S}, title = {Genomic and Phenomic Research in the 21st Century.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {29-41}, doi = {10.1016/j.tig.2018.09.007}, pmid = {30342790}, issn = {0168-9525}, support = {K22 LM011938/LM/NLM NIH HHS/United States ; R01 GM114128/GM/NIGMS NIH HHS/United States ; }, abstract = {The field of human genomics has changed dramatically over time. Initial genomic studies were predominantly restricted to rare disorders in small families. Over the past decade, researchers changed course from family-based studies and instead focused on common diseases and traits in populations of unrelated individuals. With further advancements in biobanking, computer science, electronic health record (EHR) data, and more affordable high-throughput genomics, we are experiencing a new paradigm in human genomic research. Rapidly changing technologies and resources now make it possible to study thousands of diseases simultaneously at the genomic level. This review will focus on these advancements as scientists begin to incorporate phenome-wide strategies in human genomic research to understand the etiology of human diseases and develop new drugs to treat them.}, } @article {pmid30342578, year = {2018}, author = {Frierson, PR}, title = {Towards a research program in Kantian positive psychology.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {89-98}, doi = {10.1016/j.shpsa.2017.07.005}, pmid = {30342578}, issn = {0039-3681}, } @article {pmid30342577, year = {2018}, author = {Kraus, KT}, title = {The soul as the 'guiding idea' of psychology: Kant on scientific psychology, systematicity, and the idea of the soul.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {77-88}, doi = {10.1016/j.shpsa.2017.11.010}, pmid = {30342577}, issn = {0039-3681}, } @article {pmid30342576, year = {2018}, author = {van den Berg, H}, title = {Kant and the scope of analogy in the life sciences.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {67-76}, doi = {10.1016/j.shpsa.2017.07.007}, pmid = {30342576}, issn = {0039-3681}, abstract = {In the present paper I investigate the role that analogy plays in eighteenth-century biology and in Kant's philosophy of biology. I will argue that according to Kant, biology, as it was practiced in the eighteenth century, is fundamentally based on analogical reflection. However, precisely because biology is based on analogical reflection, biology cannot be a proper science. I provide two arguments for this interpretation. First, I argue that although analogical reflection is, according to Kant, necessary to comprehend the nature of organisms, it is also necessarily insufficient to fully comprehend the nature of organisms. The upshot of this argument is that for Kant our understanding of organisms is necessarily limited. Second, I argue that Kant did not take biology to be a proper science because biology was based on analogical arguments. I show that Kant stemmed from a philosophical tradition that did not assign analogical arguments an important justificatory role in natural science. Analogy, according to this conception, does not provide us with apodictically certain cognition. Hence, sciences based on analogical arguments cannot constitute proper sciences.}, } @article {pmid30342575, year = {2018}, author = {Cohen, A}, title = {Kant on science and normativity.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {6-12}, doi = {10.1016/j.shpsa.2018.03.002}, pmid = {30342575}, issn = {0039-3681}, abstract = {The aim of this paper is to explore Kant's account of normativity through the prism of the distinction between the natural and the human sciences. Although the pragmatic orientation of the human sciences is often defined in contrast with the theoretical orientation of the natural sciences, I show that they are in fact regulated by one and the same norm, namely reason's demand for autonomy.}, } @article {pmid30342574, year = {2018}, author = {De Bianchi, S}, title = {The stage on which our ingenious play is performed: Kant's epistemology of Weltkenntnis.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {58-66}, doi = {10.1016/j.shpsa.2018.06.006}, pmid = {30342574}, issn = {0039-3681}, abstract = {This paper focuses on Kant's account of physical geography and his theory of the Earth. In spelling out the epistemological foundations of Kant's physical geography, the paper examines 1) their connection to the mode of holding-to-be-true, mathematical construction and empirical certainty and 2) their implications for Kant's view of cosmopolitan right. Moreover, by showing the role played by the mathematical model of the Earth for the foundations of Kant's Doctrine of Right, the exact relationship between the latter and physical geography is highlighted. Finally, this paper shows how, in Kant's view, the progress of physical geography can be assured if and only if the free circulation of human beings is established and regulated by law. Therefore, examining the mutual relationship between the theory of Earth and the foundations of right opens new perspectives on the relationship between epistemology and practical philosophy within Kant's system.}, } @article {pmid30342573, year = {2018}, author = {Everett, J}, title = {A Kantian account of mathematical modelling and the rationality of scientific theory change: The role of the equivalence principle in the development of general relativity.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {45-57}, doi = {10.1016/j.shpsa.2018.06.009}, pmid = {30342573}, issn = {0039-3681}, } @article {pmid30342572, year = {2018}, author = {Pringe, H}, title = {Maimon's criticism of Kant's doctrine of mathematical cognition and the possibility of metaphysics as a science.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {35-44}, doi = {10.1016/j.shpsa.2017.07.006}, pmid = {30342572}, issn = {0039-3681}, abstract = {The aim of this paper is to discuss Maimon's criticism of Kant's doctrine of mathematical cognition. In particular, we will focus on the consequences of this criticism for the problem of the possibility of metaphysics as a science. Maimon criticizes Kant's explanation of the synthetic a priori character of mathematics and develops a philosophical interpretation of differential calculus according to which mathematics and metaphysics become deeply interwoven. Maimon establishes a parallelism between two relationships: on the one hand, the mathematical relationship between the integral and the differential and on the other, the metaphysical relationship between the sensible and the supersensible. Such a parallelism will be the clue to the Maimonian solution to the Kantian problem of the possibility of metaphysics as a science.}, } @article {pmid30342571, year = {2018}, author = {Engelhard, K}, title = {The problem of grounding natural modality in Kant's account of empirical laws of nature.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {24-34}, doi = {10.1016/j.shpsa.2018.06.007}, pmid = {30342571}, issn = {0039-3681}, abstract = {One of the central problems of Kant's account of the empirical laws of nature is: What grounds their necessity? In this article I discuss the three most important lines of interpretation and suggest a novel version of one of them. While the first interpretation takes the transcendental principles as the only sources of the empirical laws' necessity, the second interpretation takes the systematicity of the laws to guarantee their necessity. It is shown that both views involve serious problems. The third interpretation, the "causal powers interpretation", locates the source of the laws' necessity in the properties of natural objects. Although the second and third interpretations seem incompatible, I analyse why Kant held both views and I argue that they can be reconciled, because the metaphysical grounding project of the laws' necessity is accounted for by Kant's causal powers account, while his best system account explains our epistemic access to the empirical laws. If, however, causal powers are supposed to fulfil the grounding function for the laws' natural modality, then I suggest that a novel reading of the causal powers interpretation should be formulated along the lines of a genuine dispositionalist conception of the laws of nature.}, } @article {pmid30342570, year = {2018}, author = {Falkenburg, B}, title = {Kant and the scope of the analytic method.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {13-23}, doi = {10.1016/j.shpsa.2018.06.005}, pmid = {30342570}, issn = {0039-3681}, abstract = {The paper investigates Kant's pre-critical views on the use of analytic and synthetic methods in Newtonian science and in philosophical reasoning. In his 1755/56 writings, Kant made use of two variants of the analytic method, i.e., conceptual analysis in a Cartesian (or Leibnizean) sense, and analysis of the phenomena in a Newtonian sense. His Prize Essay (1764) defends Newton's analytic method of physics as appropriate for philosophy, in contradistinction to the synthetic method of mathematics. A closer look, however, shows that Kant does not identify Newton's method with conceptual analysis, but just suggests a methodological analogy between both methods. Kant's 1768 paper on incongruent counterparts also fits in with his pre-critical use of conceptual analysis. Here, Kant criticizes Leibniz' relational concept of space, arguing that it is incompatible with the phenomenon of chiral objects. Since this result was in conflict with his pre-critical views about space, Kant abandoned the analytic method of philosophy in favour of his critical method. The paper closes by comparing Kant's pre-critical analytic method and the way in which he once again took up the methodological analogy between Newtonian science and metaphysics, in the preface B to the Critique of Pure Reason, in the context of his thought experiment of pure reason.}, } @article {pmid30342569, year = {2018}, author = {De Bianchi, S and Kraus, K}, title = {Introduction to Kant's philosophy of science: Bridging the gap between the natural and the human sciences.}, journal = {Studies in history and philosophy of science}, volume = {71}, number = {}, pages = {1-5}, doi = {10.1016/j.shpsa.2018.08.001}, pmid = {30342569}, issn = {0039-3681}, } @article {pmid30342557, year = {2018}, author = {Lager, S and de Goffau, MC and Sovio, U and Peacock, SJ and Parkhill, J and Stephen Charnock-Jones, D and Smith, GCS}, title = {Correction to: Detecting eukaryotic microbiota with single-cell sensitivity in human tissue.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {188}, pmid = {30342557}, issn = {2049-2618}, abstract = {The author reported an error in an equation in the article [1].}, } @article {pmid30342550, year = {2018}, author = {Endalamaw, A and Engeda, EH and Tezera, N}, title = {Incidence of tuberculosis in children on antiretroviral therapy: a retrospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {745}, pmid = {30342550}, issn = {1756-0500}, mesh = {Adolescent ; Anti-Retroviral Agents/*therapeutic use ; Child ; Child, Preschool ; Comorbidity ; Ethiopia/epidemiology ; Female ; Follow-Up Studies ; HIV Infections/*drug therapy/*epidemiology ; Humans ; Infant ; Male ; Retrospective Studies ; Tuberculosis/*epidemiology ; }, abstract = {OBJECTIVES: Be aware of the burden of tuberculosis among high-risk population is important. Three hundred fifty-two children were participated in this study. Survival analysis was conducted. We assessed the incidence of tuberculosis and its predictors in children on ART.

RESULTS: Tuberculosis incidence rate in children on ART was 2.63 per 100 person-years. Those children who were on baseline World Health Organization clinical stages 3 and 4 (AHR (adjusted hazard ratio) = 3.0; 95% CI 1.2-7.7), "fair" and "poor" ART adherence (AHR = 4.0; 95% CI 1.5-10.8), late initiation of ART (AHR = 4.0; 95% CI 1.5-10.6), and less than 6 months duration on ART (AHR = 5.5; 95% CI 1.5-20.6) were more likely to develop tuberculosis infection. The incidence rate of TB in children on ART was high. This study suggests a need to give attention to advanced AIDS stages and improve timely initiation of ART and level of adherence to ART.}, } @article {pmid30342547, year = {2018}, author = {Sasaki, S and Ukawa, S and Okada, E and Wenjing, Z and Kishi, T and Sakamoto, A and Tamakoshi, A}, title = {Comparison of a new wrist-worn accelerometer with a commonly used triaxial accelerometer under free-living conditions.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {746}, pmid = {30342547}, issn = {1756-0500}, support = {15k21316//Grant-in-Aid for young Scientists from the Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Accelerometry/*instrumentation/methods/*standards ; Adult ; *Exercise ; Female ; Humans ; Male ; Middle Aged ; Monitoring, Ambulatory/*instrumentation/methods/*standards ; Reproducibility of Results ; }, abstract = {OBJECTIVE: The Life Microscope is a new wristband-based life recorder system that can identify various human movements. We aimed to compare physical activity data captured using the Life Microscope with data from a commonly used accelerometer.

RESULTS: Twenty-nine participants (34.6 ± 12.5 years) wore both the Life Microscope and an Active Style Pro accelerometer for 7 days. Physical activity categories were calculated by converting daily accelerometer data output into time spent at sedentary, light, moderate, and vigorous physical activity. Correlations between the physical activity category and step count data obtained from the two accelerometers were assessed using Pearson correlations, paired t-tests, intra-class coefficients, and the Bland-Altman method. Our results showed good reliability between the physical activity patterns and daily step counts obtained using both devices. Bland-Altman analysis showed good agreement between data from both accelerometers. In conclusion, both accelerometers were comparable in their measurement of step counts and time spent in different physical activity intensities under free-living conditions, and either could be used for population studies.}, } @article {pmid30342519, year = {2018}, author = {Conrad, T and Kniemeyer, O and Henkel, SG and Krüger, T and Mattern, DJ and Valiante, V and Guthke, R and Jacobsen, ID and Brakhage, AA and Vlaic, S and Linde, J}, title = {Module-detection approaches for the integration of multilevel omics data highlight the comprehensive response of Aspergillus fumigatus to caspofungin.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {88}, pmid = {30342519}, issn = {1752-0509}, abstract = {BACKGROUND: Omics data provide deep insights into overall biological processes of organisms. However, integration of data from different molecular levels such as transcriptomics and proteomics, still remains challenging. Analyzing lists of differentially abundant molecules from diverse molecular levels often results in a small overlap mainly due to different regulatory mechanisms, temporal scales, and/or inherent properties of measurement methods. Module-detecting algorithms identifying sets of closely related proteins from protein-protein interaction networks (PPINs) are promising approaches for a better data integration.

RESULTS: Here, we made use of transcriptome, proteome and secretome data from the human pathogenic fungus Aspergillus fumigatus challenged with the antifungal drug caspofungin. Caspofungin targets the fungal cell wall which leads to a compensatory stress response. We analyzed the omics data using two different approaches: First, we applied a simple, classical approach by comparing lists of differentially expressed genes (DEGs), differentially synthesized proteins (DSyPs) and differentially secreted proteins (DSePs); second, we used a recently published module-detecting approach, ModuleDiscoverer, to identify regulatory modules from PPINs in conjunction with the experimental data. Our results demonstrate that regulatory modules show a notably higher overlap between the different molecular levels and time points than the classical approach. The additional structural information provided by regulatory modules allows for topological analyses. As a result, we detected a significant association of omics data with distinct biological processes such as regulation of kinase activity, transport mechanisms or amino acid metabolism. We also found a previously unreported increased production of the secondary metabolite fumagillin by A. fumigatus upon exposure to caspofungin. Furthermore, a topology-based analysis of potential key factors contributing to drug-caused side effects identified the highly conserved protein polyubiquitin as a central regulator. Interestingly, polyubiquitin UbiD neither belonged to the groups of DEGs, DSyPs nor DSePs but most likely strongly influenced their levels.

CONCLUSION: Module-detecting approaches support the effective integration of multilevel omics data and provide a deep insight into complex biological relationships connecting these levels. They facilitate the identification of potential key players in the organism's stress response which cannot be detected by commonly used approaches comparing lists of differentially abundant molecules.}, } @article {pmid30342485, year = {2018}, author = {Avila, LM and Obeidat, W and Earl, H and Niu, X and Hargreaves, W and Lukens, L}, title = {Shared and genetically distinct Zea mays transcriptome responses to ongoing and past low temperature exposure.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {761}, pmid = {30342485}, issn = {1471-2164}, mesh = {*Cold Temperature ; Environment ; *Gene Expression Profiling ; Genotype ; Glucose/biosynthesis ; Photosynthesis/genetics ; RNA, Messenger/genetics/metabolism ; Signal Transduction/genetics ; Transcription, Genetic ; Up-Regulation ; Zea mays/cytology/enzymology/*genetics/metabolism ; }, abstract = {BACKGROUND: Cold temperatures and their alleviation affect many plant traits including the abundance of protein coding gene transcripts. Transcript level changes that occur in response to cold temperatures and their alleviation are shared or vary across genotypes. In this study we identify individual transcripts and groups of functionally related transcripts that consistently respond to cold and its alleviation. Genes that respond differently to temperature changes across genotypes may have limited functional importance. We investigate if these genes share functions, and if their genotype-specific gene expression levels change in magnitude or rank across temperatures.

RESULTS: We estimate transcript abundances from over 22,000 genes in two unrelated Zea mays inbred lines during and after cold temperature exposure. Genotype and temperature contribute to many genes' abundances. Past cold exposure affects many fewer genes. Genes up-regulated in cold encode many cytokinin glucoside biosynthesis enzymes, transcription factors, signalling molecules, and proteins involved in diverse environmental responses. After cold exposure, protease inhibitors and cuticular wax genes are newly up-regulated, and environmentally responsive genes continue to be up-regulated. Genes down-regulated in response to cold include many photosynthesis, translation, and DNA replication associated genes. After cold exposure, DNA replication and translation genes are still preferentially downregulated. Lignin and suberin biosynthesis are newly down-regulated. DNA replication, reactive oxygen species response, and anthocyanin biosynthesis genes have strong, genotype-specific temperature responses. The ranks of genotypes' transcript abundances often change across temperatures.

CONCLUSIONS: We report a large, core transcriptome response to cold and the alleviation of cold. In cold, many of the core suite of genes are up or downregulated to control plant growth and photosynthesis and limit cellular damage. In recovery, core responses are in part to prepare for future stress. Functionally related genes are consistently and greatly up-regulated in a single genotype in response to cold or its alleviation, suggesting positive selection has driven genotype-specific temperature responses in maize.}, } @article {pmid30342483, year = {2018}, author = {Hamvas, A and Feng, R and Bi, Y and Wang, F and Bhattacharya, S and Mereness, J and Kaushal, M and Cotten, CM and Ballard, PL and Mariani, TJ and , }, title = {Exome sequencing identifies gene variants and networks associated with extreme respiratory outcomes following preterm birth.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {94}, pmid = {30342483}, issn = {1471-2156}, support = {HHSN268201100037C/HL/NHLBI NIH HHS/United States ; R01 HL105702/HL/NHLBI NIH HHS/United States ; U01 HL101813/HL/NHLBI NIH HHS/United States ; HL101798//National Institute of Heart Lung & Blood/ ; U01 HL101798/HL/NHLBI NIH HHS/United States ; K08 AI108870/AI/NIAID NIH HHS/United States ; U01 HL101465/HL/NHLBI NIH HHS/United States ; U01 HL101800/HL/NHLBI NIH HHS/United States ; U01 HL101456/HL/NHLBI NIH HHS/United States ; U01 HL101794/HL/NHLBI NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; HHSN268201100037C//National Institute of Heart Lung & Blood/ ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, abstract = {BACKGROUND: Previous studies have identified genetic variants associated with bronchopulmonary dysplasia (BPD) in extremely preterm infants. However, findings with genome-wide significance have been rare, and not replicated. We hypothesized that whole exome sequencing (WES) of premature subjects with extremely divergent phenotypic outcomes could facilitate the identification of genetic variants or gene networks contributing disease risk.

RESULTS: The Prematurity and Respiratory Outcomes Program (PROP) recruited a cohort of > 765 extremely preterm infants for the identification of markers of respiratory morbidity. We completed WES on 146 PROP subjects (85 affected, 61 unaffected) representing extreme phenotypes of early respiratory morbidity. We tested for association between disease status and individual common variants, screened for rare variants exclusive to either affected or unaffected subjects, and tested the combined association of variants across gene loci. Pathway analysis was performed and disease-related expression patterns were assessed. Marginal association with BPD was observed for numerous common and rare variants. We identified 345 genes with variants unique to BPD-affected preterm subjects, and 292 genes with variants unique to our unaffected preterm subjects. Of these unique variants, 28 (19 in the affected cohort and 9 in unaffected cohort) replicate a prior WES study of BPD-associated variants. Pathway analysis of sets of variants, informed by disease-related gene expression, implicated protein kinase A, MAPK and Neuregulin/epidermal growth factor receptor signaling.

CONCLUSIONS: We identified novel genes and associated pathways that may play an important role in susceptibility/resilience for the development of lung disease in preterm infants.}, } @article {pmid30342477, year = {2018}, author = {Liu, X and Zhang, R and Ou, H and Gui, Y and Wei, J and Zhou, H and Tan, H and Li, Y}, title = {Comprehensive transcriptome analysis reveals genes in response to water deficit in the leaves of Saccharum narenga (Nees ex Steud.) hack.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {250}, pmid = {30342477}, issn = {1471-2229}, support = {31101195//National Natural Science Foundation of China/ ; 2013AA102604//National High Technology Research and Development Program of China/ ; 16-389-18//Guangxi Special Funds for Bagui Scholars and Distinguished Experts, Funds of Guangxi/ ; gjnytxgxcxtd-03//Fund for Guangxi Innovation Teams of Modern Agriculture Technology/ ; }, mesh = {Dehydration ; Droughts ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Gene Library ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; Molecular Sequence Annotation ; Plant Leaves/genetics/physiology ; Plant Proteins/genetics ; RNA, Plant/genetics ; Saccharum/*genetics/physiology ; Stress, Physiological ; *Transcriptome ; Water/physiology ; }, abstract = {BACKGROUND: Sugarcane is an important sugar and energy crop that is widely planted in the world. Among the environmental stresses, the water-deficit stress is the most limiting to plant productivity. Some groups have used PCR-based and microarray technologies to investigate the gene expression changes of multiple sugarcane cultivars under water stress. Our knowledge about sugarcane genes in response to water deficit is still poor.

RESULTS: A wild sugarcane type, Saccharum narenga, was selected and treated with drought stress for 22 days. Leaves from drought treated (DTS) and control (CK) plants were obtained for deep sequencing. Paired-end sequencing enabled us to assemble 104,644 genes (N50 = 1605 bp), of which 38,721 were aligned to other databases, such as UniProt, NR, GO, KEGG and Pfam. Single-end and paired-end sequencing identified 30,297 genes (> 5 TPM) in all samples. Compared to CK, 3389 differentially expressed genes (DEGs) were identified in DTS samples, comprising 1772 up-regulated and 1617 down-regulated genes. Functional analysis showed that the DEGs were involved in biological pathways like response to blue light, metabolic pathways and plant hormone signal transduction. We further observed the expression patterns of several important gene families, including aquaporins, late embryogenesis abundant proteins, auxin related proteins, transcription factors (TFs), heat shock proteins, light harvesting chlorophyll a-b binding proteins, disease resistance proteins, and ribosomal proteins. Interestingly, the regulation of genes varied among different subfamilies of aquaporin and ribosomal proteins. In addition, DIVARICATA and heat stress TFs were first reported in sugarcane leaves in response to water deficit. Further, we showed potential miRNAs that might be involved in the regulation of gene changes in sugarcane leaves under the water-deficit stress.

CONCLUSIONS: This is the first transcriptome study of Saccharum narenga and the assembled genes are a valuable resource for future research. Our findings will improve the understanding of the mechanism of gene regulation in sugarcane leaves under the water-deficit stress. The output of this study will also contribute to the sugarcane breeding program.}, } @article {pmid30342468, year = {2018}, author = {Deng, S and Lira, M and Huang, D and Wang, K and Valdez, C and Kinong, J and Rejto, PA and Bienkowska, J and Hardwick, J and Xie, T}, title = {TNER: a novel background error suppression method for mutation detection in circulating tumor DNA.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {387}, pmid = {30342468}, issn = {1471-2105}, mesh = {Circulating Tumor DNA/*genetics ; Computer Simulation ; DNA Mutational Analysis/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation/*genetics ; Neoplasms/genetics ; Normal Distribution ; ROC Curve ; Software ; }, abstract = {BACKGROUND: Ultra-deep next-generation sequencing of circulating tumor DNA (ctDNA) holds great promise as a tool for the early detection of cancer and for monitoring disease progression and therapeutic responses. However, the low abundance of ctDNA in the bloodstream coupled with technical errors introduced during library construction and sequencing complicates mutation detection.

RESULTS: To achieve high accuracy of variant calling via better distinguishing low-frequency ctDNA mutations from background errors, we introduce TNER (Tri-Nucleotide Error Reducer), a novel background error suppression method that provides a robust estimation of background noise to reduce sequencing errors. The results on both simulated data and real data from healthy subjects demonstrate that the proposed algorithm consistently outperforms a current, state-of-the-art, position-specific error polishing model, particularly when the sample size of healthy subjects is small.

CONCLUSIONS: TNER significantly enhances the specificity of downstream ctDNA mutation detection without sacrificing sensitivity. The tool is publicly available at https://github.com/ctDNA/TNER .}, } @article {pmid30342465, year = {2018}, author = {Singh, AK and Chaurasia, S and Kumar, S and Singh, R and Kumari, J and Yadav, MC and Singh, N and Gaba, S and Jacob, SR}, title = {Identification, analysis and development of salt responsive candidate gene based SSR markers in wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {249}, pmid = {30342465}, issn = {1471-2229}, support = {SERB/LS-8/2014//SERB/ ; National Innovations in Climate Resilient Agriculture (NICRA) Project code 1006607//Indian Council of Agricultural Research/ ; }, mesh = {Alleles ; Chromosome Mapping ; *Genetic Variation ; Genotype ; Microsatellite Repeats/genetics ; Phenotype ; Phylogeny ; Salinity ; Salt Tolerance ; Triticum/*genetics/physiology ; }, abstract = {BACKGROUND: Salinity severely limits wheat production in many parts of the world. Development of salt tolerant varieties represents the most practical option for enhancing wheat production from these areas. Application of marker assisted selection may assist in fast tracking development of salt tolerant wheat varieties. However, SSR markers available in the public domain are not specifically targeted to functional regions of wheat genome, therefore large numbers of these need to be analysed for identification of markers associated with traits of interest. With the availability of a fully annotated wheat genome assembly, it is possible to develop SSR markers specifically targeted to genic regions. We performed extensive analysis to identify candidate gene based SSRs and assessed their utility in characterizing molecular diversity in a panel of wheat genotypes.

RESULTS: Our analysis revealed, 161 SSR motifs in 94 salt tolerance candidate genes of wheat. These SSR motifs were nearly equally distributed on the three wheat sub-genomes; 29.8% in A, 35.7% in B and 34.4% in D sub-genome. The maximum number of SSR motifs was present in exons (31.1%) followed by promoters (29.8%), 5'UTRs (21.1%), introns (14.3%) and 3'UTRs (3.7%). Out of the 65 candidate gene based SSR markers selected for validation, 30 were found polymorphic based on initial screening and employed for characterizing genetic diversity in a panel of wheat genotypes including salt tolerant and susceptible lines. These markers generated an average of 2.83 alleles/locus. Phylogenetic analysis revealed four clusters. Salt susceptible genotypes were mainly represented in clusters I and III, whereas high and moderate salt tolerant genotypes were distributed in the remaining two clusters. Population structure analysis revealed two sub-populations, sub-population 1 contained the majority of salt tolerant whereas sub-population 2 contained majority of susceptible genotypes. Moreover, we observed reasonably higher transferability of SSR markers to related wheat species.

CONCLUSION: We have developed salt responsive gene based SSRs in wheat for the first time. These were highly useful in unravelling functional diversity among wheat genotypes with varying responses to salt stress. The identified gene based SSR markers will be valuable genomic resources for genetic/association mapping of salinity tolerance in wheat.}, } @article {pmid30342229, year = {2019}, author = {Visser, JH and Bennett, NC and Jansen van Vuuren, B}, title = {Evolutionary and ecological patterns within the South African Bathyergidae: Implications for taxonomy.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {181-197}, doi = {10.1016/j.ympev.2018.10.017}, pmid = {30342229}, issn = {1095-9513}, abstract = {The family Bathyergidae (comprising six genera) is a group of subterranean rodents endemic to sub-Saharan Africa. Our understanding of the evolution and species richness of the South African bathyergid genera Georychus, Bathyergus and Cryptomys is limited, with the majority of species listed as Least Concern by the IUCN Red List of Threatened Species. Genetic data suggest that several cryptic species may be present in these genera. To explore genetic and ecological distinctiveness, and evaluate taxonomic richness across the ranges of Georychus, Bathyergus and to a lesser degree, Cryptomys, as well as evaluate possible scenarios which have historically influenced evolutionary patterns, we employed four protein coding markers (one mitochondrial and three nuclear) along with distribution wide sampling schemes and large sample sizes. In addition, possible ecological differences among the different intra-generic clades were explored. Genera appear to have originated in the north-eastern interior of South Africa, following novel habitats created through the Post-African I erosion cycle and dramatic changes in climate and phytogeography. In each genus, multiple geographically discrete genetic lineages (clades) are supported by both the mitochondrial and nuclear data. These lineages bear signature of the fragmentation of wider historical distributions through major environmental changes since the middle Miocene (major uplift events, Post-African II erosion cycle, drainage evolution of major river systems, sea-level fluctuations as well as climatic changes and vegetation shifts), thereby leading to long-term isolation. Along with protracted periods of separation, it appears that ecological differences further delimit the lineages in relation to geology, phytogeographic preference, elevation, rainfall and temperature. As such, two lineages in Georychus (Clades 1 and 2) and one lineages in Cryptomys (Clade I) occur at higher elevations above the Great Escarpment (in older deposits harbouring grassland vegetation, with higher rainfall and lower daily temperatures), with the remaining lineages within these genera (Clades 3, 4 and 5 in Georychus and Clades III and IV in Cryptomys) occupying a low-land distribution with contrasting climatic and geological characteristics. Although significant differences in ecological variables were also observed between Bathyergus clades, these were not consistent, given their largely low-land distributions. Our results corroborate and expand previous suggestions that several cryptic species are present within the South African Bathyergidae.}, } @article {pmid30342038, year = {2018}, author = {Bartz, M and Gola, EM}, title = {Meristem development and activity in gametophytes of the model fern, Ceratopteris richardii.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {107-115}, doi = {10.1016/j.ydbio.2018.10.005}, pmid = {30342038}, issn = {1095-564X}, abstract = {Ceratopteris richardii is a model fern species widely used to analyze various developmental processes and their regulation in gametophytes. The form of mature C. richardii gametophytes depends on the activity of the marginal meristem, but knowledge on meristem formation and structure is limited. Therefore, we analyzed cellular events accompanying the development of gametophytes using cell lineage and proliferation analyses to explain the establishment and functioning of the marginal meristem. We show that: i) gametophytes are devoid of the apical initial cell or the apical cell-based meristem in the early developmental stages; ii) the cells that are predestined to form the marginal meristem divide according to a stable pattern; iii) only one transient initial cell is present in the marginal meristem, and the selection of a new functioning initial cell is related to a stable sequence of its divisions. Our results contribute to a better understanding of the developmental events underlying gametophyte growth and marginal meristem functioning in Ceratopteris. The principles, which were established in this study and enabled the identification of functioning initial cells, can be applied to analyze genetic and/or physiological mechanism(s) governing meristem maintenance in vascular plants, both in developmental and evolutionary contexts.}, } @article {pmid30341989, year = {2018}, author = {Furman, BLS and Dang, UJ and Evans, BJ and Golding, GB}, title = {Divergent subgenome evolution after allopolyploidization in African clawed frogs (Xenopus).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1945-1958}, doi = {10.1111/jeb.13391}, pmid = {30341989}, issn = {1420-9101}, support = {CGSD3-475567-2015//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2015-04477//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2017-05770//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN/283102-2012//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Whole genome duplication (WGD), the doubling of the nuclear DNA of a species, contributes to biological innovation by creating genetic redundancy. One mode of WGD is allopolyploidization, wherein each genome from two ancestral species becomes a 'subgenome' of a polyploid descendant species. The evolutionary trajectory of a duplicated gene that arises from WGD is influenced both by natural selection that may favour redundant, new or partitioned functions, and by gene silencing (pseudogenization). Here, we explored how these two phenomena varied over time and within allopolyploid genomes in several allotetraploid clawed frog species (Xenopus). Our analysis demonstrates that, across these polyploid genomes, purifying selection was greatly relaxed compared to a diploid outgroup, was asymmetric between each subgenome, and that coding regions are shorter in the subgenome with more relaxed purifying selection. As well, we found that the rate of gene loss was higher in the subgenome under weaker purifying selection and that this rate has remained relatively consistent over time after WGD. Our findings provide perspective from recently evolved vertebrates on the evolutionary forces that likely shape allopolyploid genomes on other branches of the tree of life.}, } @article {pmid30341452, year = {2019}, author = {Amberkar, U and Khandeparker, R and Parab, P}, title = {Nitrate Reductase Gene Expression in Idiomarina Strain cos21 Obtained from Oxygen Minimum Zone of Arabian Sea.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {63-69}, doi = {10.1007/s00284-018-1585-y}, pmid = {30341452}, issn = {1432-0991}, abstract = {This study analyses the induction and repression of nitrate reduction activity in a batch culture of Idiomarina strain cos21. On a change from aerobic to anaerobic respiration, the culture entered a stationary phase. The onset of this phase showed 3.75 fold increase in mRNA levels for the nitrate reductase enzyme. mRNA accumulated very rapidly during a short period, after which its overall concentration declined to reach a lower value. The level of nitrite reductase protein reached a maximum value at 36 h of growth when the oxygen concentration dropped below 10 µM. The data set provided here confer new insights into the understanding of the physiological response of Idiomarina strain cos21 to change in oxygen concentration allowing the bacterium to survive and adapt to a new environment by dissimilatory reduction of nitrate to nitrite, which serves to provide energy as the bacteria adapt to anaerobiosis. Main strategy used here is to induce, measure, and track the expression of microbial genes, while they grow in culture conditions to better mimic interaction in a natural environment. This study will help us with a better understanding of the nitrate reduction process in the oxygen minimum zone.}, } @article {pmid30341451, year = {2019}, author = {Fraunhofer, ME and Geißler, AJ and Behr, J and Vogel, RF}, title = {Comparative Genomics of Lactobacillus brevis Reveals a Significant Plasmidome Overlap of Brewery and Insect Isolates.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {37-47}, doi = {10.1007/s00284-018-1581-2}, pmid = {30341451}, issn = {1432-0991}, support = {AiF 18194 N//German Ministry of Economics/ ; }, abstract = {Lactobacillus (L.) brevis represents a versatile, ubiquitistic species of lactic acid bacteria, occurring in various foods, as well as plants and intestinal tracts. The ability to deal with considerably differing environmental conditions in the respective ecological niches implies a genomic adaptation to the particular requirements to use it as a habitat beyond a transient state. Given the isolation source, 24 L. brevis genomes were analyzed via comparative genomics to get a broad view of the genomic complexity and ecological versatility of this species. This analysis showed L. brevis being a genetically diverse species possessing a remarkably large pan genome. As anticipated, it proved difficult to draw a correlation between chromosomal settings and isolation source. However, on plasmidome level, brewery- and insect-derived strains grouped into distinct clusters, referable to a noteworthy gene sharing between both groups. The brewery-specific plasmidome is characterized by several genes, which support a life in the harsh environment beer, but 40% of the brewery plasmidome were found in insect-derived strains as well. This suggests a close interaction between these habitats. Further analysis revealed the presence of a truncated horC cluster version in brewery- and insect-associated strains. This disproves horC, the major contributor to survival in beer, as brewery isolate specific. We conclude that L. brevis does not perform rigorous chromosomal changes to live in different habitats. Rather it appears that the species retains a certain genetic diversity in the plasmidome and meets the requirements of a particular ecological niche with the acquisition of appropriate plasmids.}, } @article {pmid30341443, year = {2018}, author = {Zhernakova, DV and Le, TH and Kurilshikov, A and Atanasovska, B and Bonder, MJ and Sanna, S and Claringbould, A and Võsa, U and Deelen, P and Franke, L and de Boer, RA and Kuipers, F and Netea, MG and Hofker, MH and Wijmenga, C and Zhernakova, A and Fu, J and , and , }, title = {Author Correction: Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1752}, doi = {10.1038/s41588-018-0275-9}, pmid = {30341443}, issn = {1546-1718}, abstract = {In the version of this paper originally published, there was a typographical error. In the Discussion, the sentence "In line with this, Ep-CAM-deficient mice exhibited increased intestinal permeability and decreased ion transport60, which may contribute to CVD susceptibility risk59" originally read iron instead of ion transport. This error has been corrected in the HTML, PDF and print versions of the article.}, } @article {pmid30341441, year = {2018}, author = {Burgess, DJ}, title = {Navigating mouse cell types.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {739}, doi = {10.1038/s41576-018-0067-1}, pmid = {30341441}, issn = {1471-0064}, } @article {pmid30341440, year = {2018}, author = {Rees, HA and Liu, DR}, title = {Publisher Correction: Base editing: precision chemistry on the genome and transcriptome of living cells.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {801}, doi = {10.1038/s41576-018-0068-0}, pmid = {30341440}, issn = {1471-0064}, abstract = {The originally published article contained errors in reference numbering throughout table 1 (DNA base editors and their approximate editing windows) due to the unintended propagation of reference numbering from an earlier version of the table. The article has now been corrected online. The editors apologize for this error.}, } @article {pmid30341439, year = {2018}, author = {Koch, L}, title = {Altered splicing in Alzheimer transcriptomes.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {738-739}, doi = {10.1038/s41576-018-0064-4}, pmid = {30341439}, issn = {1471-0064}, } @article {pmid30341225, year = {2018}, author = {Ledgerwood, A}, title = {The preregistration revolution needs to distinguish between predictions and analyses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10516-E10517}, pmid = {30341225}, issn = {1091-6490}, } @article {pmid30341224, year = {2018}, author = {Nosek, BA and Ebersole, CR and DeHaven, AC and Mellor, DT}, title = {Reply to Ledgerwood: Predictions without analysis plans are inert.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10518}, pmid = {30341224}, issn = {1091-6490}, } @article {pmid30341223, year = {2018}, author = {Webster, DG}, title = {Strengthening sustainability through data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11118-11120}, pmid = {30341223}, issn = {1091-6490}, mesh = {*Fisheries ; }, } @article {pmid30341222, year = {2018}, author = {Atkins, JF}, title = {Culmination of a half-century quest reveals insight into mutant tRNA-mediated frameshifting after tRNA departure from the decoding site.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11121-11123}, pmid = {30341222}, issn = {1091-6490}, mesh = {Anticodon ; Codon ; *Frameshifting, Ribosomal ; Nucleic Acid Conformation ; RNA, Transfer/*genetics ; Ribosomes ; }, } @article {pmid30341221, year = {2018}, author = {Carruthers, P}, title = {Young children flexibly attribute mental states to others.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11351-11353}, pmid = {30341221}, issn = {1091-6490}, } @article {pmid30341220, year = {2018}, author = {Bhimsaria, D and Rodríguez-Martínez, JA and Pan, J and Roston, D and Korkmaz, EN and Cui, Q and Ramanathan, P and Ansari, AZ}, title = {Specificity landscapes unmask submaximal binding site preferences of transcription factors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10586-E10595}, pmid = {30341220}, issn = {1091-6490}, support = {R01 GM120625/GM/NIGMS NIH HHS/United States ; T32 HG002760/HG/NHGRI NIH HHS/United States ; }, abstract = {We have developed Differential Specificity and Energy Landscape (DiSEL) analysis to comprehensively compare DNA-protein interactomes (DPIs) obtained by high-throughput experimental platforms and cutting edge computational methods. While high-affinity DNA binding sites are identified by most methods, DiSEL uncovered nuanced sequence preferences displayed by homologous transcription factors. Pairwise analysis of 726 DPIs uncovered homolog-specific differences at moderate- to low-affinity binding sites (submaximal sites). DiSEL analysis of variants of 41 transcription factors revealed that many disease-causing mutations result in allele-specific changes in binding site preferences. We focused on a set of highly homologous factors that have different biological roles but "read" DNA using identical amino acid side chains. Rather than direct readout, our results indicate that DNA noncontacting side chains allosterically contribute to sculpt distinct sequence preferences among closely related members of transcription factor families.}, } @article {pmid30341219, year = {2018}, author = {Dethoff, EA and Boerneke, MA and Gokhale, NS and Muhire, BM and Martin, DP and Sacco, MT and McFadden, MJ and Weinstein, JB and Messer, WB and Horner, SM and Weeks, KM}, title = {Pervasive tertiary structure in the dengue virus RNA genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11513-11518}, pmid = {30341219}, issn = {1091-6490}, support = {R01 AI125416/AI/NIAID NIH HHS/United States ; F32 GM128330/GM/NIGMS NIH HHS/United States ; T32 CA009156/CA/NCI NIH HHS/United States ; F32 GM103180/GM/NIGMS NIH HHS/United States ; R35 GM122532/GM/NIGMS NIH HHS/United States ; R43 AI129095/AI/NIAID NIH HHS/United States ; T32 CA009111/CA/NCI NIH HHS/United States ; U54 AI057157/AI/NIAID NIH HHS/United States ; }, abstract = {RNA virus genomes are efficient and compact carriers of biological information, encoding information required for replication both in their primary sequences and in higher-order RNA structures. However, the ubiquity of RNA elements with higher-order folds-in which helices pack together to form complex 3D structures-and the extent to which these elements affect viral fitness are largely unknown. Here we used single-molecule correlated chemical probing to define secondary and tertiary structures across the RNA genome of dengue virus serotype 2 (DENV2). Higher-order RNA structures are pervasive and involve more than one-third of nucleotides in the DENV2 genomic RNA. These 3D structures promote a compact overall architecture and contribute to viral fitness. Disrupting RNA regions with higher-order structures leads to stable, nonreverting mutants and could guide the development of vaccines based on attenuated RNA viruses. The existence of extensive regions of functional RNA elements with tertiary folds in viral RNAs, and likely many other messenger and noncoding RNAs, means that there are significant regions with pocket-containing surfaces that may serve as novel RNA-directed drug targets.}, } @article {pmid30341218, year = {2018}, author = {Guerin, ME and Stirnemann, G and Giganti, D}, title = {Conformational entropy of a single peptide controlled under force governs protease recognition and catalysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11525-11530}, pmid = {30341218}, issn = {1091-6490}, abstract = {An immense repertoire of protein chemical modifications catalyzed by enzymes is available as proteomics data. Quantifying the impact of the conformational dynamics of the modified peptide remains challenging to understand the decisive kinetics and amino acid sequence specificity of these enzymatic reactions in vivo, because the target peptide must be disordered to accommodate the specific enzyme-binding site. Here, we were able to control the conformation of a single-molecule peptide chain by applying mechanical force to activate and monitor its specific cleavage by a model protease. We found that the conformational entropy impacts the reaction in two distinct ways. First, the flexibility and accessibility of the substrate peptide greatly increase upon mechanical unfolding. Second, the conformational sampling of the disordered peptide drives the specific recognition, revealing force-dependent reaction kinetics. These results support a mechanism of peptide recognition based on conformational selection from an ensemble that we were able to quantify with a torsional free-energy model. Our approach can be used to predict how entropy affects site-specific modifications of proteins and prompts conformational and mechanical selectivity.}, } @article {pmid30341217, year = {2018}, author = {Charlebois, DA and Hauser, K and Marshall, S and Balázsi, G}, title = {Multiscale effects of heating and cooling on genes and gene networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10797-E10806}, pmid = {30341217}, issn = {1091-6490}, support = {F31 GM101946/GM/NIGMS NIH HHS/United States ; R35 GM122561/GM/NIGMS NIH HHS/United States ; }, abstract = {Most organisms must cope with temperature changes. This involves genes and gene networks both as subjects and agents of cellular protection, creating difficulties in understanding. Here, we study how heating and cooling affect expression of single genes and synthetic gene circuits in Saccharomyces cerevisiae We discovered that nonoptimal temperatures induce a cell fate choice between stress resistance and growth arrest. This creates dramatic gene expression bimodality in isogenic cell populations, as arrest abolishes gene expression. Multiscale models incorporating population dynamics, temperature-dependent growth rates, and Arrhenius scaling of reaction rates captured the effects of cooling, but not those of heating in resistant cells. Molecular-dynamics simulations revealed how heating alters the conformational dynamics of the TetR repressor, fully explaining the experimental observations. Overall, nonoptimal temperatures induce a cell fate decision and corrupt gene and gene network function in computationally predictable ways, which may aid future applications of engineered microbes in nonstandard temperatures.}, } @article {pmid30340868, year = {2018}, author = {Götmark, F and Cafaro, P and O'Sullivan, J}, title = {Aging Human Populations: Good for Us, Good for the Earth.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {851-862}, doi = {10.1016/j.tree.2018.08.015}, pmid = {30340868}, issn = {1872-8383}, abstract = {As the nations of the world grapple with the task of creating sustainable societies, ending and in some cases reversing population growth will be necessary to succeed. Yet stable or declining populations are typically reported in the media as a problem, or even a crisis, due to demographic aging. This is misguided, as economic analyses show that the costs connected with aging societies are manageable, while the economic, social, and environmental benefits of smaller populations are substantial. Earth's human-carrying capacity has been exceeded; hence, population growth must end and aging societies are unavoidable. They should be embraced as part of a just and prosperous future for people and the other species with whom we share our planet.}, } @article {pmid30340649, year = {2018}, author = {Kadia, BM and Chichom-Mefire, A and Halle-Ekane, GE}, title = {Exploring the role of obesity and overweight in predicting postoperative outcome of abdominal surgery in a sub-Saharan African setting: a prospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {742}, pmid = {30340649}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Appendectomy/adverse effects/statistics & numerical data ; Cameroon/epidemiology ; Female ; *Herniorrhaphy/adverse effects/statistics & numerical data ; Humans ; Male ; Middle Aged ; Obesity/complications/epidemiology ; Overweight/*complications/epidemiology ; Postoperative Complications/epidemiology/*etiology ; Prospective Studies ; *Uterine Myomectomy/adverse effects/statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: Current literature on the role of excess weight in predicting surgical outcome is controversial. In sub-Saharan Africa, there is extreme paucity of data regarding this issue in spite of the increasing rates of obesity and overweight in the region. This prospective cohort study, carried out over a period of 4 months at Limbe Regional Hospital in the Southwest region of Cameroon, assessed 30-day postoperative outcome of abdominal surgery among consecutive adults with body mass index (BMI) ≥ 25 kg/m2. Adverse postoperative events were reported as per Clavien-Dindo classification.

RESULTS: A total of 103 patients were enrolled. Of these, 68.9% were female. The mean age was 38.2 ± 13.7 years. Sixty-four (62.1%) of the patients were overweight and the mean BMI was 29.2 ±4.3 kg/m2. The physical status scores of the patients were either I or II. Appendectomy, myomectomy and hernia repair were the most performed procedures. The overall complication rate was 13/103 (12.6%), with 61.5% being Clavien-Dindo grades II or higher. From the lowest to the highest BMI category, there was a significant increase in the proportion of patients with complications; 25-29.9 kg/m2: 6.25%, 30-34.9 kg/m2: 18.75%, 35-39.9 kg/m2: 25.0%, and ≥ 40 kg/m2: 66.70%; p = 0.0086.}, } @article {pmid30340646, year = {2018}, author = {Tadesse, S and Kahsay, T and Adhanom, G and Kahsu, G and Legese, H and G/Wahid, A and Derbie, A}, title = {Prevalence, antimicrobial susceptibility profile and predictors of asymptomatic bacteriuria among pregnant women in Adigrat General Hospital, Northern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {740}, pmid = {30340646}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; *Ampicillin Resistance ; Asymptomatic Infections/*epidemiology ; Bacteriuria/*epidemiology/*microbiology ; Ethiopia/epidemiology ; Female ; Hospitals, General ; Humans ; Microbial Sensitivity Tests ; Middle Aged ; Pregnancy ; Pregnancy Complications, Infectious/*epidemiology/*microbiology ; Prevalence ; *Vancomycin Resistance ; Young Adult ; }, abstract = {OBJECTIVE: Approach to asymptomatic bacteriuria among pregnant women in Ethiopia is mainly based on clinical grounds and urine strip and microscopy tests. On top of this, the treatment is also on an empirical basis which may leads to an increased antimicrobial resistance. The aim of this study was to assess the prevalence, antimicrobial susceptibility profile and associated factors of asymptomatic bacteriuria among pregnant women attending antenatal clinic in Adigrat Hospital, Northern Ethiopia.

RESULTS: Out of 259 pregnant women included in the study, the prevalence of asymptomatic bacteriuria was at 55 (21.2%). Gram negative bacteria, specifically Escherichia coli were the predominant isolates followed by Klebsiella species and Proteus mirabilis. Of the Gram positive identified bacteria, Staphylococcus aureus was main isolate. Age of the mother (18-25 years old) with [AOR = 8.5, 95% CI (2.2, 32.9)], family income (< 1000 ETB) with [AOR = 7.5, 95% CI = (2.4, 23.1)] and gestational period at 1st trimester [AOR = 11.9, 95% CI (4.4, 32.4)] and 2nd trimester [AOR; 5.6, 95% CI (2.0, 15.5%)] were predictors significantly associated with asymptomatic bacteriuria. All Gram negative isolates were found 100% resistance to Ampicllin. Moreover, all Gram positive isolates were found sensitive to Vancomycin at 100%.}, } @article {pmid30340634, year = {2018}, author = {Ikhsan, M and Hiedayati, N and Maeyama, K and Nurwidya, F}, title = {Nigella sativa as an anti-inflammatory agent in asthma.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {744}, pmid = {30340634}, issn = {1756-0500}, mesh = {Animals ; Anti-Inflammatory Agents/administration & dosage/*pharmacology ; Asthma/*drug therapy/prevention & control ; Ethanol ; Histamine/*metabolism ; Mast Cells/*drug effects ; *Nigella sativa ; Peritoneal Cavity ; Plant Extracts/administration & dosage/*pharmacology ; Rats ; Rats, Wistar ; Seeds ; }, abstract = {OBJECTIVE: Nigella sativa (N. sativa) has several pharmacological actions which include antioxidant, antidiabetic, anticancer, antitussive, immunomodulator, analgesic, antimicrobial, anti-inflammatory, spasmolytic, and bronchodilator. The purpose of this study is to measure the effectivity of N. sativa ethanol extract as anti-inflammation on peritoneal Wistar rat mast cells. The laboratory experiment was used to investigate the effectivity of N. sativa as an anti-inflammatory on mast cells. Six groups of mast cells were stimulated by C 48/80 to release histamine. Group 1 were without N. sativa, while group 2, 3, 4, 5, and 6 were given N. sativa with concentrations of 0.1 mg/ml, 0.2 mg/ml, 0.3 mg/ml, 0.4 mg/ml and 0.5 mg/ml, respectively. Histamine concentration was measured by high-performance liquid chromatography-fluorometry.

RESULT: The study showed that N. sativa ethanol extract effectively inhibit histamine release from peritoneal Wistar rat mast cells proportionally to its concentration. N. sativa is effective as an anti-inflammation on mast cells by inhibition of histamine release and has no toxic effect on mast cell. N. sativa could be considered as a potential therapy for asthma therapy and prevention.}, } @article {pmid30340631, year = {2018}, author = {Li, HY and Wang, H and Wang, HT and Xin, PY and Xu, XH and Ma, Y and Liu, WP and Teng, CY and Jiang, CL and Lou, LP and Arnold, W and Cralle, L and Zhu, YG and Chu, JF and Gilbert, JA and Zhang, ZJ}, title = {The chemodiversity of paddy soil dissolved organic matter correlates with microbial community at continental scales.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {187}, pmid = {30340631}, issn = {2049-2618}, abstract = {BACKGROUND: Paddy soil dissolved organic matter (DOM) represents a major hotspot for soil biogeochemistry, yet we know little about its chemodiversity let alone the microbial community that shapes it. Here, we leveraged ultrahigh-resolution mass spectrometry, amplicon, and metagenomic sequencing to characterize the molecular distribution of DOM and the taxonomic and functional microbial diversity in paddy soils across China. We hypothesized that variances in microbial community significantly associate with changes in soil DOM molecular composition.

RESULTS: We report that both microbial and DOM profiles revealed geographic patterns that were associated with variation in mean monthly precipitation, mean annual temperature, and pH. DOM molecular diversity was significantly correlated with microbial taxonomic diversity. An increase in DOM molecules categorized as peptides, carbohydrates, and unsaturated aliphatics, and a decrease in those belonging to polyphenolics and polycyclic aromatics, significantly correlated with proportional changes in some of the microbial taxa, such as Syntrophobacterales, Thermoleophilia, Geobacter, Spirochaeta, Gaiella, and Defluviicoccus. DOM composition was also associated with the relative abundances of the microbial metabolic pathways, such as anaerobic carbon fixation, glycolysis, lignolysis, fermentation, and methanogenesis.

CONCLUSIONS: Our study demonstrates the continental-scale distribution of DOM is significantly correlated with the taxonomic profile and metabolic potential of the rice paddy microbiome. Abiotic factors that have a distinct effect on community structure can also influence the chemodiversity of DOM and vice versa. Deciphering these associations and the underlying mechanisms can precipitate understanding of the complex ecology of paddy soils, as well as help assess the effects of human activities on biogeochemistry and greenhouse gas emissions in paddy soils.}, } @article {pmid30340629, year = {2018}, author = {Khalil, A and Omran, H and Alsheikh, F}, title = {Balance of pro- and anti-inflammatory cytokines in livers of high fat diet rats exposed to fractionated gamma irradiation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {741}, pmid = {30340629}, issn = {1756-0500}, mesh = {Animals ; Cytokines/*metabolism ; Diet, High-Fat/*adverse effects ; Disease Models, Animal ; Gamma Rays/*adverse effects ; Inflammation/*etiology/immunology/metabolism ; Liver/immunology/metabolism/*radiation effects ; Male ; Rats ; Rats, Wistar ; Whole-Body Irradiation/*adverse effects ; }, abstract = {OBJECTIVE: In this work, the effects of irradiation and high fat diet (HFD) intake have been examined in Wistar rat livers. HFD Wistar rats were exposed three times per week for 2 months to three different doses (0.5, 1, and 2 Gy) of a fractionated whole body gamma irradiation (FWBGI). Hepatic mRNA of these rats was evaluated for five cytokines, TNFα, IL1β, IL6, CRP and IL10. In addition, some critical protein levels were evaluated.

RESULTS: Results demonstrated that FWBGI was able to omit the inflammatory state already induced by the HFD through the depression of all pro-inflammatory genes. In addition, TNFα/IL10 IL1β/IL10, IL6/IL10 and CRP/IL10 ratios were less than 1 at all studied irradiation doses. IL6/IL10 ratio (mRNA and protein) was the best that represented an anti-inflammatory state with all used doses. Results could be of great importance in liver radiotherapy in HFD animal models and may give indicators about the inflammatory state improvement during FWBGI.}, } @article {pmid30340622, year = {2018}, author = {Haftu, A and Hagos, H and Mehari, MA and G/Her, B}, title = {Health care providers' adherence to immediate postpartum care guideline and associated factors among women who gave birth in Mekele public teaching hospitals, Tigray 2018.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {743}, pmid = {30340622}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Ethiopia ; Female ; Guideline Adherence/*statistics & numerical data ; Hospitals, Teaching/*statistics & numerical data ; Humans ; Midwifery/*statistics & numerical data ; Nurses/*statistics & numerical data ; Postnatal Care/*statistics & numerical data ; Pregnancy ; Prenatal Care/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: To assess health care providers adherence to immediate postpartum care and associated factors among women's who gave birth in Mekele teaching public hospitals, 2018.

RESULTS: The Health care providers' complete adherence to immediate postpartum care guideline was 22.8%. Health care providers who have complete adherence to prenatal care guideline were 93.3% less likely to have incomplete adherence to immediate postpartum care guideline (AOR 95% CI 0.067 (0.036-0.125)).}, } @article {pmid30340566, year = {2018}, author = {Vieira, VMNCS and Lopes, IE and Creed, JC}, title = {The biomass-density relationship in seagrasses and its use as an ecological indicator.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {44}, pmid = {30340566}, issn = {1472-6785}, support = {UID/EEA/50009/2013//Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa/International ; UID/EEA/50009/2013//Faculdade de Ciências e Tecnologia, Universidade Nova de Lisboa/International ; Ciências do Mar 1137/2010//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/International ; FAPERJ-E-26/111.574/2014//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/International ; E26/201.286/2014//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/International ; CNPq- 307117/2014-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; }, abstract = {BACKGROUND: Biomass-density relations have been at the centre of a search for an index which describes the health of seagrass meadows. However, this search has been complicated by the intricacy of seagrass demographics and their complex biomass-density relations, a consequence mainly of their modular growth and clonality. Concomitantly, biomass-density upper boundaries have been determined for terrestrial plants and algae, reflecting their asymptotic maximum efficiencies of space occupation. Each stand's distance to its respective biomass-density upper boundary reflects its effective efficiency in packing biomass, which has proved a reliable ecological indicator in order to discriminate between taxonomic groups, functional groups and clonal vs. non-clonal growth.

RESULTS: We gathered data from 32 studies on 10 seagrass species distributed worldwide and demonstrated that seagrasses are limited by their own boundary line, placed below the boundaries previously determined for algae and terrestrial plants. Then, we applied a new metric-dgrass: each stand's perpendicular distance to the seagrass boundary-and used this parameter to review fundamental aspects such as clonal growth patterns, depth distribution, seasonality, interspecific competition, and the effects of light, temperature and nutrients.

CONCLUSIONS: Seagrasses occupy space less efficiently than algae and terrestrial plants. Using only their biomass and density data we established a new and efficient tool to describe space occupation by seagrasses. This was used with success to evaluate their meadows as an ecological indicator for the health of coastal ecosystems.}, } @article {pmid30340540, year = {2018}, author = {Zhang, L and Wu, P and Lu, W and Lü, S}, title = {Molecular mechanism of the extended oil accumulation phase contributing to the high seed oil content for the genotype of tung tree (Vernicia fordii).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {248}, pmid = {30340540}, issn = {1471-2229}, support = {31500267//National Natural Science Foundation of China/ ; 2017YFD0600703//National Key R&D Program of China/ ; 631631k0231//Natural Science Foundation of Hubei Province/ ; }, mesh = {Aleurites/*genetics/metabolism ; Fatty Acids/analysis/*metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Genotype ; Plant Oils/analysis/*metabolism ; Seeds/genetics/metabolism ; Sequence Analysis, RNA ; *Transcriptome ; Trees ; }, abstract = {BACKGROUND: Oil from seeds of the tung tree (Vernicia fordii) has unique drying properties that are industrially important. We found that the extended oil accumulation period was related to the high seed oil content at maturity among tung tree population. In order to understand the molecular mechanism underlying the high oil content in tung tree seed, Tree H and L were adopted for the further investigation, with seed oil content of about 70 and 45%, respectively. We compared the transcriptomic changes of seed at various times during oil accumulation between the two trees.

RESULTS: Transcriptomes analysis revealed that many genes involved in glycolysis, fatty acid synthesis, and tri-acyl glyceride assembly still kept high expression in the late period of seed oil accumulation for Tree H only. Many genes in fatty acid degradation pathway were largely up regulated in the late period of seed oil accumulation for Tree L only. Four transcription factors related to fatty acid biosynthesis had different expression pattern in the seed oil accumulation period for the two trees. WRI1 was down regulated and kept the low expression in the late period of seed oil accumulation for the two trees. PII, LEC1 and LEC1-LIKE extended the high expression in the late period of seed oil accumulation in Tree H only.

CONCLUSIONS: The continued accumulation of oil in the late period of seed oil accumulation for Tree H was associated with relatively high expression of the relevant genes in glycolysis, fatty acid synthesis and tri-acyl glyceride assembly. PII, LEC1, and LEC1-LIKE rather than WRI1 should play an important role in the oil continual accumulation in the late period of seed oil accumulation in Tree H. This study provides novel insight into the variation in seed oil content and informs plant breeding strategies to maximize oil yield.}, } @article {pmid30340538, year = {2018}, author = {Tang, T and Wu, Y and Lin, H and Li, Y and Zuo, H and Gao, Q and Wang, C and Pei, X}, title = {The drug tolerant persisters of Riemerella anatipestifer can be eradicated by a combination of two or three antibiotics.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {137}, pmid = {30340538}, issn = {1471-2180}, support = {2016M602691//China Postdoctoral Science Foundation (CN)/ ; 2017JY0240//Department of Science and Technology of Sichuan Province/ ; 2016SCU11005//Sichuan University/ ; 2017ZX10103010-002//Ministry of Science and Technology of the People's Republic of China (CN)/ ; 31570924//Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Riemerella anatipestifer (RA), the causative agent of duck infectious serositis, leads to high mortality in duck flocks and great economic losses in duck industry. Previous studies on RA are largely focused on its detection, virulence factors, serology, epidemiology as well as antibiotic resistance. Neither drug tolerant persisters nor the persister level under the treatment of antibiotics has been revealed. The persisters are non-growing or dormant cells within an isogenic bacterial population; they play important roles in recurrent infection and formation of drug resistant mutants. The aim of this study is to detect the drug tolerant persisters from the exponentially grown population of RA reference strain (RA 11845) or RA clinical isolate (RA TQ3), and address whether a single antibiotic or a combination of two or three antimicrobials can eradicate the persisters at respective maximum serum/plasma concentration (Cmax).

RESULT: With the concentration of a test antibiotic increased, a small fraction of cells in the exponentially grown culture of RA reference strain (RA 11845) or RA clinical isolate (RA TQ3) always survived, irrespective of treatment time, indicating the presence of drug tolerant presisters. A single antibiotic cannot eradicate the persisters of both RA strains at respective Cmax, except that the Cmax of ceftiofur wiped out the population of the reference strain (RA 11845). Besides, the clinical isolate RA TQ3 presented a higher tolerance to ceftiofur in comparison to that of the reference strain (RA 11845). Combination of any two or three antimicrobials eliminated the drug tolerant persisters of RA TQ3 completely at respective Cmax.

CONCLUSION: A sub-community of drug tolerant persisters was present in RA population. Persisters of RA TQ3 are single drug tolerant and not multidrug tolerant persisters.}, } @article {pmid30340536, year = {2018}, author = {Verster, AJ and Borenstein, E}, title = {Competitive lottery-based assembly of selected clades in the human gut microbiome.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {186}, pmid = {30340536}, issn = {2049-2618}, support = {R01 GM124312/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: While the composition of the gut microbiome has now been well described by several large-scale studies, models that can account for the range of microbiome compositions that have been observed are still lacking. One model that has been well studied in macro communities and that could be useful for understanding microbiome assembly is the competitive lottery model. This model posits that groups of organisms from a regional pool of species are able to colonize the same niche and that the first species to arrive will take over the entire niche, excluding other group members.

RESULTS: Here, we examined whether this model also plays a role in the assembly of the human gut microbiome, defining measures to identify groups of organisms whose distribution across samples conforms to the competitive lottery schema. Applying this model to multiple datasets with thousands of human gut microbiome samples, we identified several taxonomic groups that exhibit a lottery-like distribution, including the Akkermansia, Dialister, and Phascolarctobacterium genera. We validated that these groups exhibit lottery-like assembly in multiple independent microbiome datasets confirming that this assembly schema is universal and not cohort specific. Examining the distribution of species from these groups in the gut microbiome of developing infants, we found that the initial lottery winner can be replaced by a different member of the group. We further found that species from lottery-like groups tend to have fewer genes in their genomes, suggesting more specialized species that are less able to engage in niche differentiation.

CONCLUSIONS: Combined, our findings highlight the complex and dynamic process through which microbial communities assemble and suggest that different phylogenetic groups may follow different models during this process.}, } @article {pmid30340527, year = {2018}, author = {Davis, RL and Choi, G and Kuiken, T and Quéré, P and Trapp, S and Short, KR and Richard, M}, title = {The culture of primary duck endothelial cells for the study of avian influenza.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {138}, pmid = {30340527}, issn = {1471-2180}, support = {DE180100512//Australian Research Council DECRA/ ; 727922//Horizon 2020/ ; }, abstract = {BACKGROUND: Endothelial cells play a major role in highly pathogenic avian influenza (HPAI) virus pathogenesis in gallinaceous poultry species (e.g. chicken, turkey and quail). Upon infection of gallinaceous poultry with HPAI viruses, endothelial cells throughout the body become rapidly infected, leading to systemic dissemination of the virus, disseminated intravascular coagulation, oedema and haemorrhaging. In contrast, the pathogenesis of HPAI viruses in most wild bird species (e.g. duck, goose and gull species) is not associated with endothelial tropism. Indeed, viral antigen is not found in the endothelial cells of most wild bird species following infection with HPAI viruses. This differential endothelial cell tropism in avian species is poorly understood, mainly due to the absence of appropriate cell culture systems.

RESULTS: Here, we describe the isolation and purification of primary duck endothelial cells from the aorta or bone marrow of Pekin duck embryos. Cells were differentiated in the presence of vascular endothelial growth factor and, if needed, enriched via fluorescent-activated cell sorting based on the uptake of acetylated low-density lipoprotein. The expression of von Willebrand factor, a key marker of endothelial cells, was confirmed by polymerase chain reaction. Monocultures of duck endothelial cells, either derived from the aorta or the bone marrow, were susceptible to infection with an H5N1 HPAI virus but to a much lesser extent than chicken endothelial cells.

CONCLUSIONS: The methods described herein to isolate and purify duck endothelial cells from the aorta or bone marrow could also be applied to obtain microvascular endothelial cells from other tissues and organs, such as the lung or the intestine, and represent a valuable tool to study the pathogenesis of avian viruses.}, } @article {pmid30340523, year = {2018}, author = {Abu Zaitoun, SY and Jamous, RM and Shtaya, MJ and Mallah, OB and Eid, IS and Ali-Shtayeh, MS}, title = {Characterizing Palestinian snake melon (Cucumis melo var. flexuosus) germplasm diversity and structure using SNP and DArTseq markers.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {246}, pmid = {30340523}, issn = {1471-2229}, support = {M32-016.//Middle East Regional Cooperation Program (MERC)-USAID/ ; }, mesh = {Bayes Theorem ; Cucumis melo/*genetics ; Gene Pool ; Genetic Markers ; *Genetic Variation ; Genotype ; Geography ; Polymorphism, Single Nucleotide/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Crop landraces embody a source of beneficial genes potentially providing endurance to environmental stress and other agronomic qualities including yield. Our study included 88 snake melon accessions (Cucumis melo var. flexuosus) collected from 9 districts in the Palestinian West-Bank. These accessions represent four landraces of Palestinian snake melon: Green, and White Baladi, and Green, and White Sahouri.

RESULTS: This is the first report on successful application of genotyping by sequencing in snake melon. Nine thousand seven hundred fifty single-nucleotide polymorphism (SNP) and 7400 DArTseq genetic markers were employed to evaluate genetic biodiversity and population structure of Palestinian snake melon germplasm collection. Clustering based on neighbor-joining-analysis, principle coordinate and Bayesian model implemented in Structure showed that patterns of genetic diversity of snake melon landraces depends on their geographical source and unraveled the presence of two major local landraces (Sahouri, and Baladi) with accessions from each group clustering together. A significant correlation was observed between both types of markers in Mantel correlation test. A significant association between genetic and geographic matrices (P < 0.0001) was also detected. AMOVA indicated that majority of variation (90%) was due to the difference within accessions.

CONCLUSION: The Palestinian landraces seem to have unique genes that may allow the enhancement of the global snake melon gene pool and developments of the plant production worldwide. Our subsequent objective is to detect genotypes with promising qualities and to conduct association mapping studies concentrating on Fusarium-wilt resistance, yield, and environmental stresses.}, } @article {pmid30340522, year = {2018}, author = {Ghaderifar, S and Najafpoor, AA and Zarrinfar, H and Esmaily, H and Hajialilo, E}, title = {Isolation and identification of Acanthamoeba from pond water of parks in a tropical and subtropical region in the Middle East, and its relation with physicochemical parameters.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {139}, pmid = {30340522}, issn = {1471-2180}, support = {Authors would like to thanks from MUMS for the financial support.//The current study is an approved proposal in Mashhad University of Medical Sciences (MUMS) with the code 940310./ ; }, abstract = {BACKGROUND: Free-living amoeba (FLA) are wide-spread protozoa that are found in different environmental sources including water, soil, dust, hospital units and ventilation areas. These amoebas can act as opportunistic or non-opportunistic pathogens. Among FLAs, some genera such as Acanthamoeba are important because of their potential pathogenic ability in humans. The purpose of this study is to identify of Acanthamoeba isolated from pond water of parks in a tropical and subtropical region in the Middle East, and its relation with physicochemical parameters.From August to December 2015, 90 samples were collected from pond water of parks of 13 regions of Mashhad City. Physicochemical parameters were measured in situ. After filtering, the samples were cultured on Bacto-agar enriched with Escherichia coli. PCR analysis was conducted on the culture-positive samples, and then the PCR products were sequenced. Statistical analysis was performed by SPSS software and Fisher's Exact and Mann-Whitney test.

RESULTS: Among the samples that were examined, 19 samples (21.1%) were positive for Acanthamoeba. The sequencing revealed that Acanthamoeba isolates belonged to T4 genotype of Acanthamoeba. There was no significant relationship between physicochemical parameters and the presence of Acanthamoeba.

CONCLUSION: The prevalence of Acanthamoeba in pond water of parks was relatively high, but there was no significant relationship between physicochemical parameters and the presence of Acanthamoeba.}, } @article {pmid30340521, year = {2018}, author = {Yang, T and Yu, Q and Xu, W and Li, DZ and Chen, F and Liu, A}, title = {Transcriptome analysis reveals crucial genes involved in the biosynthesis of nervonic acid in woody Malania oleifera oilseeds.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {247}, pmid = {30340521}, issn = {1471-2229}, support = {31700285 and 31571709//National Natural Science Foundation of China/ ; 2018FB037//Applied Basic Research Foundation of Yunnan Province/ ; }, mesh = {Fatty Acids, Monounsaturated/*metabolism ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; Lipid Metabolism ; Olacaceae/chemistry/*genetics ; Plant Oils/chemistry/*metabolism ; Seeds/chemistry/genetics ; Sequence Analysis, RNA ; *Transcriptome ; Triglycerides/metabolism ; }, abstract = {BACKGROUND: Malania oleifera Chun et Lee (Olacaceae), an evergreen broad-leaved woody tree native to southwest China, is an important oilseed tree. Its seed oil has a high level of nervonic acid (cis-tetracos-15-enoic acid, over 60%), which is essential for human health. M. oleifera seed oil is a promising source of nervonic acid, but little is known about the physiological and molecular mechanisms underlying its biosynthesis.

RESULTS: In this study, we recorded oil accumulation at four stages of seed development. Using a high-throughput RNA-sequencing technique, we obtained 55,843 unigenes, of which 29,176 unigenes were functionally annotated. By comparison, 22,833 unigenes had a two-fold or greater expression at the fast oil accumulation stage than at the initial stage. Of these, 198 unigenes were identified as being functionally involved in diverse lipid metabolism processes (including de novo fatty acid synthesis, carbon chain elongation and modification, and triacylglycerol assembly). Key genes (encoding KCS, KCR, HCD and ECR), putatively responsible for nervonic acid biosynthesis, were isolated and their expression profiles during seed development were confirmed by quantitative real-time PCR analysis. Also, we isolated regulatory factors (such as WRI1, ABI3 and FUS3) that are putatively involved in the regulation of oil biosynthesis and seed development.

CONCLUSION: Our results provide novel data on the physiological and molecular mechanisms of nervonic acid biosynthesis and oil accumulation in M. oleifera seeds, and will also serve as a starting point for biotechnological genetic engineering for the production of nervonic acid resources.}, } @article {pmid30340520, year = {2018}, author = {Feng, B and Zhang, C and Chen, T and Zhang, X and Tao, L and Fu, G}, title = {Salicylic acid reverses pollen abortion of rice caused by heat stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {245}, pmid = {30340520}, issn = {1471-2229}, support = {2017YFD0300106//National Food Science and Technology Project/ ; 31561143003//National Natural Science Foundation of China/ ; 31671619//National Natural Science Foundation of China/ ; LQ18C130003//Zhejiang Provincial Natural Science Foundation, China/ ; }, mesh = {Apoptosis ; *Heat-Shock Response ; Hot Temperature ; Hydrogen Peroxide/*metabolism ; Meiosis ; Oryza/*physiology ; Pollen/physiology ; Reactive Oxygen Species/metabolism ; Salicylic Acid/*metabolism ; Seeds/physiology ; }, abstract = {BACKGROUND: Extremely high temperatures are becoming an increasingly severe threat to crop yields. It is well documented that salicylic acid (SA) can enhance the stress tolerance of plants; however, its effect on the reproductive organs of rice plants has not been described before. To investigate the mechanism underlying the SA-mediated alleviation of the heat stress damage to rice pollen viability, a susceptible cultivar (Changyou1) was treated with SA at the pollen mother cell (PMC) meiosis stage and then subjected to heat stress of 40 °C for 10 d until 1d before flowering.

RESULTS: Under control conditions, no significant difference was found in pollen viability and seed-setting rate in SA treatments. However, under heat stress conditions, SA decreased the accumulation of reactive oxygen species (ROS) in anthers to prevent tapetum programmed cell death (PCD) and degradation. The genes related to tapetum development, such as EAT1 (Eternal Tapetum 1), MIL2 (Microsporeless 2), and DTM1 (Defective Tapetum and Meiocytese 1), were found to be involved in this process. When rice plants were exogenously sprayed with SA or paclobutrazol (PAC, a SA inhibitor) + H2O2 under heat stress, a significantly higher pollen viability was found compared to plants sprayed with H2O, PAC, or SA + dimethylthiourea (DMTU, an H2O2 and OH· scavenger). Additionally, a sharp increase in H2O2 was observed in the SA or PAC+ H2O2 treatment groups compared to other treatments.

CONCLUSION: We suggest that H2O2 may play an important role in mediating SA to prevent pollen abortion caused by heat stress through inhibiting the tapetum PCD.}, } @article {pmid30340512, year = {2018}, author = {Zhao, L and Han, L and Xiao, C and Lin, X and Xu, C and Yang, C}, title = {Rapid and pervasive development- and tissue-specific homeolog expression partitioning in newly formed inter-subspecific rice segmental allotetraploids.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {756}, pmid = {30340512}, issn = {1471-2164}, support = {31670218//National Natural Science Foundation of China/ ; 31300192//National Natural Science Foundation of China/ ; 20160520062JH//Youth Science Foundation of Technology of Technology Development plan of Jilin Provincial Government/ ; }, mesh = {*Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Hybridization, Genetic ; Oryza/*genetics/*growth & development ; *Polyploidy ; *Sequence Homology, Nucleic Acid ; Time Factors ; }, abstract = {BACKGROUND: In diverse plant taxa, whole-genome duplication (WGD) events are major sources of phenotypic novelty. Studies of gene expression in synthetic polyploids have shown immediate expression and functional partitioning of duplicated genes among different tissues. Many studies of the tissue-specific homeolog expression partitioning have focused on allopolyploids that have very different parental genomes, while few studies have focused on autopolyploids or allopolyploids that have similar parental genomes.

RESULTS: In this study, we used a set of reciprocal F1 hybrids and synthetic tetraploids constructed from subspecies (japonica and indica) of Asian rice (Oryza sativa L.) as a model to gain insights into the expression partitioning of homeologs among tissues in a developmental context. We assayed the tissue-specific silencing (TSS) of the parental homeologs of 30 key genes in the hybrids and tetraploids relative to the in vitro "hybrids" (parental mixes) using Sequenom MassARRAY. We found that the parental mix and synthetic tetraploids had higher frequencies of homeolog TSS than the F1, revealing an instantaneous role of WGD on homeolog expression partitioning.

CONCLUSIONS: Our observations contradicted those of previous studies in which newly formed allopolyploids had a low TSS frequency, similar to that of F1 hybrids, suggesting that the impact of WGD on homeolog expression requires a longer time to manifest. In addition, we found that the TSS frequency in the tetraploids varied at different growth stages and that roots had a much higher frequency of TSS than leaves, which indicated that developmental and metabolic traits may influence the expression states of duplicated genes in newly formed plant polyploids.}, } @article {pmid30340511, year = {2018}, author = {Tran, NTL and Huang, CH}, title = {MODSIDE: a motif discovery pipeline and similarity detector.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {755}, pmid = {30340511}, issn = {1471-2164}, support = {P200A130153//U.S. Department of Education Graduate Fellowships in Areas of National Need (GAANNs)/ ; }, mesh = {*Amino Acid Motifs ; Animals ; Computational Biology/*methods ; Humans ; Mice ; Sequence Alignment ; *Software ; }, abstract = {BACKGROUND: Previous studies demonstrate the usefulness of using multiple tools and methods for improving the accuracy of motif detection. Over the past years, numerous motif discovery pipelines have been developed. However, they typically report only the top ranked results either from individual motif finders or from a combination of multiple tools and algorithms.

RESULTS: Here we present MODSIDE, a motif discovery pipeline and similarity detector. The pipeline integrated four de novo motif finders: ChIPMunk, MEME, Weeder, and XXmotif. It also incorporated a motif similarity detection tool MOTIFSIM. MODSIDE was designed for delivering not only the predictive results from individual motif finders but also the comparison results for multiple tools. The results include the common significant motifs from multiple tools, the motifs detected by some tools but not by others, and the best matches for each motif in the motif collection of multiple tools. MODSIDE also possesses other useful features for merging similar motifs and clustering motifs into motif trees.

CONCLUSIONS: We evaluated MODSIDE and its adopted motif finders on 16 benchmark datasets. The statistical results demonstrate MODSIDE achieves better accuracy than individual motif finders. We also compared MODSIDE with two popular motif discovery pipelines: MEME-ChIP and RSAT peak-motifs. The comparison results reveal MODSIDE attains similar performance as RSAT peak-motifs but better accuracy than MEME-ChIP. In addition, MODSIDE is able to deliver various comparison results that are not offered by MEME-ChIP, RSAT peak-motifs, and other existing motif discovery pipelines.}, } @article {pmid30340510, year = {2018}, author = {Sharma, G and Parales, R and Singer, M}, title = {In silico characterization of a novel putative aerotaxis chemosensory system in the myxobacterium, Corallococcus coralloides.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {757}, pmid = {30340510}, issn = {1471-2164}, support = {IOS-1354562//Division of Integrative Organismal Systems/ ; }, mesh = {Chemotaxis/*genetics ; *Computer Simulation ; Cytoplasm/genetics ; Evolution, Molecular ; Genome, Bacterial/genetics ; Genomics ; Myxococcales/cytology/*genetics/*metabolism ; }, abstract = {BACKGROUND: An efficient signal transduction system allows a bacterium to sense environmental cues and then to respond positively or negatively to those signals; this process is referred to as taxis. In addition to external cues, the internal metabolic state of any bacterium plays a major role in determining its ability to reside and thrive in its current environment. Similar to external signaling molecules, cytoplasmic signals are also sensed by methyl-accepting chemotaxis proteins (MCPs) via diverse ligand binding domains. Myxobacteria are complex soil-dwelling social microbes that can perform a variety of physiologic and metabolic activities ranging from gliding motility, sporulation, biofilm formation, carotenoid and secondary metabolite biosynthesis, predation, and slime secretion. To live such complex lifestyles, they have evolved efficient signal transduction systems with numerous one- and two-component regulatory system along with a large array of chemosensory systems to perceive and integrate both external and internal cues.

RESULTS: Here we report the in silico characterization of a putative energy taxis cluster, Cc-5, which is present in only one amongst 34 known and sequenced myxobacterial genomes, Corallococcus coralloides. In addition, we propose that this energy taxis cluster is involved in oxygen sensing, suggesting that C. coralloides can sense (either directly or indirectly) and then respond to changing concentrations of molecular oxygen.

CONCLUSIONS: This hypothesis is based on the presence of a unique MCP encoded in this gene cluster that contains two different oxygen-binding sensor domains, PAS and globin. In addition, the two monooxygenases encoded in this cluster may contribute to aerobic respiration via ubiquinone biosynthesis, which is part of the cytochrome bc1 complex. Finally, we suggest that this cluster was acquired from Actinobacteria, Gammaproteobacteria or Cyanobacteria. Overall, this in silico study has identified a potentially innovative and evolved mechanism of energy taxis in only one of the myxobacteria, C. coralloides.}, } @article {pmid30340506, year = {2018}, author = {Han, YC and Lin, CM and Chen, TT}, title = {RNA-Seq analysis of differentially expressed genes relevant to innate and adaptive immunity in cecropin P1 transgenic rainbow trout (Oncorhynchus mykiss).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {760}, pmid = {30340506}, issn = {1471-2164}, mesh = {Adaptive Immunity/*genetics ; Animals ; Animals, Genetically Modified ; *Gene Expression Profiling ; Immunity, Innate/*genetics ; Molecular Sequence Annotation ; Oncorhynchus mykiss/*genetics/*immunology ; Peptides/genetics ; *Sequence Analysis, RNA ; }, abstract = {BACKGROUND: In the past years, our laboratory successfully generated transgenic rainbow trout bearing cecropin P1 transgene. These fish exhibited resistant characteristic to infection by Aeromonas salmonicida, Infectious Hematopoietic Necrosis Virus (IHNV) and Ceratomyxa shasta (a parasitic pathogen). Previously, treating rainbow trout macrophage cells (RTS-11) with cecropin B, pleurocidin and CF17, respectively, resulted in elevated expression of two pro-inflammatory genes, e.g. cyclooxygenase-2 (cox-2) and interleukin-1β (il-1β). In addition, a profiling of global gene expression by 44 k salmonid microarray analysis was conducted, and the results showed that immune relevant processes have been perturbed in cecopin P1 transgenic rainbow trout. Therefore, we hypothesized that cecropin P1 may not only eliminate pathogens directly, but also modulate the host immune systems, leading to increased resistance against pathogen infections. To confirm this hypothesis, we performed de novo mRNA deep sequencing (RNA-Seq) to analyze the transcriptomic expression profiles in three immune competent tissues of cecropin P1 transgenic rainbow trout.

RESULTS: De novo sequencing of mRNA of the rainbow trout spleen, liver and kidney tissues were conducted by second-generation Illumina system, followed by Trinity assembly. Tissue specific unigenes were obtained, and annotated according to the Gene Ontology (GO) and the Nucleotide Basic Local Alignment Search Tool (BLAST). Over 2000 differentially expressed genes (DEGs) were determined by normalized ratio of Reads Per Kilobase of transcript per million mapped reads (RPKM) among the transgenic and non-transgenic fish in a tissue specific manner, and there were 82 DEGs in common among the three tissues. In addition, the enrichment analysis according to Gene Ontology Biological Process (GO:BP), and Kyoto Encyclopedia of Genes and Genomes (KEGG) based pathway analysis associated with innate/adaptive immunity of fish were also performed to illustrate the altered immune-related functions in each tissue.

CONCLUSIONS: According to the RNA-Seq data, the correlations between alteration of gene expression profiles and the functional perturbations of the host immune processes were revealed. In comparison with the results of cDNA microarray analysis conducted by Lo et al., the overall results supported our hypothesis that the gene product of cecropin P1 transgene may not only directly eliminate pathogens, but also modulate the host immune system. Results of this study present valuable genetic information for Oncorhynchus mykiss, and will benefit future studies on the immunology of this fish species.}, } @article {pmid30340461, year = {2018}, author = {Stoney, RA and Schwartz, JM and Robertson, DL and Nenadic, G}, title = {Using set theory to reduce redundancy in pathway sets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {386}, pmid = {30340461}, issn = {1471-2105}, support = {BB/J014478/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Algorithms ; Databases, Genetic ; Gene Expression Profiling ; Humans ; Signal Transduction/*genetics ; }, abstract = {BACKGROUND: The consolidation of pathway databases, such as KEGG, Reactome and ConsensusPathDB, has generated widespread biological interest, however the issue of pathway redundancy impedes the use of these consolidated datasets. Attempts to reduce this redundancy have focused on visualizing pathway overlap or merging pathways, but the resulting pathways may be of heterogeneous sizes and cover multiple biological functions. Efforts have also been made to deal with redundancy in pathway data by consolidating enriched pathways into a number of clusters or concepts. We present an alternative approach, which generates pathway subsets capable of covering all of genes presented within either pathway databases or enrichment results, generating substantial reductions in redundancy.

RESULTS: We propose a method that uses set cover to reduce pathway redundancy, without merging pathways. The proposed approach considers three objectives: removal of pathway redundancy, controlling pathway size and coverage of the gene set. By applying set cover to the ConsensusPathDB dataset we were able to produce a reduced set of pathways, representing 100% of the genes in the original data set with 74% less redundancy, or 95% of the genes with 88% less redundancy. We also developed an algorithm to simplify enrichment data and applied it to a set of enriched osteoarthritis pathways, revealing that within the top ten pathways, five were redundant subsets of more enriched pathways. Applying set cover to the enrichment results removed these redundant pathways allowing more informative pathways to take their place.

CONCLUSION: Our method provides an alternative approach for handling pathway redundancy, while ensuring that the pathways are of homogeneous size and gene coverage is maximised. Pathways are not altered from their original form, allowing biological knowledge regarding the data set to be directly applicable. We demonstrate the ability of the algorithms to prioritise redundancy reduction, pathway size control or gene set coverage. The application of set cover to pathway enrichment results produces an optimised summary of the pathways that best represent the differentially regulated gene set.}, } @article {pmid30340458, year = {2018}, author = {Stacey, RG and Skinnider, MA and Chik, JHL and Foster, LJ}, title = {Context-specific interactions in literature-curated protein interaction databases.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {758}, pmid = {30340458}, issn = {1471-2164}, support = {214PRO//Genome Canada/ ; 214PRO//Genome British Columbia/ ; MOP77688//Canadian Institutes of Health Research/Canada ; }, mesh = {Computational Biology/*methods ; *Databases, Protein ; Protein Interaction Mapping/*methods ; }, abstract = {BACKGROUND: Databases of literature-curated protein-protein interactions (PPIs) are often used to interpret high-throughput interactome mapping studies and estimate error rates. These databases combine interactions across thousands of published studies and experimental techniques. Because the tendency for two proteins to interact depends on the local conditions, this heterogeneity of conditions means that only a subset of database PPIs are interacting during any given experiment. A typical use of these databases as gold standards in interactome mapping projects, however, assumes that PPIs included in the database are indeed interacting under the experimental conditions of the study.

RESULTS: Using raw data from 20 co-fractionation experiments and six published interactomes, we demonstrate that this assumption is often false, with up to 55% of purported gold standard interactions showing no evidence of interaction, on average. We identify a subset of CORUM database complexes that do show consistent evidence of interaction in co-fractionation studies, and we use this subset as gold standards to dramatically improve interactome mapping as judged by the number of predicted interactions at a given error rate.

CONCLUSIONS: We recommend using this CORUM subset as the gold standard set in future co-fractionation studies. More generally, we recommend using the subset of literature-curated PPIs that are specific to the experimental context whenever possible.}, } @article {pmid30340456, year = {2018}, author = {Levinstein Hallak, K and Tzur, S and Rosset, S}, title = {Big data analysis of human mitochondrial DNA substitution models: a regression approach.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {759}, pmid = {30340456}, issn = {1471-2164}, mesh = {Algorithms ; *Big Data ; DNA, Mitochondrial/*genetics ; Data Mining ; Humans ; *Models, Statistical ; Poisson Distribution ; RNA, Ribosomal/genetics ; RNA, Transfer/genetics ; Regression Analysis ; }, abstract = {BACKGROUND: We study Phylotree, a comprehensive representation of the phylogeny of global human mitochondrial DNA (mtDNA) variations, to better understand the mtDNA substitution mechanism and its most influential factors. We consider a substitution model, where a set of genetic features may predict the rate at which mtDNA substitutions occur. To find an appropriate model, an exhaustive analysis on the effect of multiple factors on the substitution rate is performed through Negative Binomial and Poisson regressions. We examine three different inclusion options for each categorical factor: omission, inclusion as an explanatory variable, and by-value partitioning. The examined factors include genes, codon position, a CpG indicator, directionality, nucleotide, amino acid, codon, and context (neighboring nucleotides), in addition to other site based factors. Partitioning a model by a factor's value results in several sub-models (one for each value), where the likelihoods of the sub-models can be combined to form a score for the entire model. Eventually, the leading models are considered as viable candidates for explaining mtDNA substitution rates.

RESULTS: Initially, we introduce a novel clustering technique on genes, based on three similarity tests between pairs of genes, supporting previous results regarding gene functionalities in the mtDNA. These clusters are then used as a factor in our models. We present leading models for the protein coding genes, rRNA and tRNA genes and the control region, showing it is disadvantageous to separate the models of transitions/transversions, or synonymous/non-synonymous substitutions. We identify a context effect that cannot be attributed solely to protein level constraints or CpG pairs. For protein-coding genes, we show that the substitution model should be partitioned into sub-models according to the codon position and input codon; additionally we confirm that gene identity and cluster have no significant effect once the above factors are accounted for.

CONCLUSIONS: We leverage the large, high-confidence Phylotree mtDNA phylogeny to develop a new statistical approach. We model the substitution rates using regressions, allowing consideration of many factors simultaneously. This admits the use of model selection tools helping to identify the set of factors best explaining the mutational dynamics when considered in tandem.}, } @article {pmid30340455, year = {2018}, author = {Patil, AS and Popovsky, S and Levy, Y and Chu, Y and Clevenger, J and Ozias-Akins, P and Hovav, R}, title = {Genetic insight and mapping of the pod constriction trait in Virginia-type peanut.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {93}, pmid = {30340455}, issn = {1471-2156}, support = {IS-5020-17//United States - Israel Binational Agricultural Research and Development Fund/ ; }, abstract = {BACKGROUND: Pod constriction is an important descriptive and agronomic trait of peanut. For the in-shell Virginia marketing-type, this trait has commercial importance as well, since deeply constricted pods have a tendency to break, which makes them unmarketable. Classical genetic studies have indicated that pod constriction in peanut is controlled by one to four genes, depending on the genetic background. In all of those studies, pod constriction was evaluated visually as opposed to quantitatively. Here, we examined the genetic nature of this trait in the Virginia-type background. Our study involved 195 recombinant inbred lines (F7RILs) derived from two closely related cultivars that differ in their degree of pod constriction. Pod constriction was evaluated visually and quantitatively in terms of the pod constriction index (PCI), calculated as the average ratio between the pod's waist and shoulders.

RESULTS: ANOVA and genetic parameters for PCI among the F7RILs in three blocks showed very significant genotypic effect (p(F) < 0.0001) and high heritability and genetic gain estimates (0.84 and 0.52, respectively). The mean PCI values of the different RILs had a bimodal distribution with an approximate 1:1 ratio between the two curves. Pod constriction was also determined visually (VPC) by grading the degree of each RIL as 'deep' or 'slight'. The χ2 test was found to not be significantly different from a 1:1 ratio (p = 0.79) as well. SNP-array-based technology was used to map this trait in the RIL population. A major locus for the pod constriction trait was found on chromosome B7, between B07_120,287,958 and B07_120,699,791, and the best-linked SNP explained 32% of the total variation within that region. Some discrepancy was found between the SNPs original location and the genetic mapping of the trait.

CONCLUSION: The trait distribution and mapping, together with data from F1 and F2 generations indicate that in this background the pod constriction is controlled by a major recessive gene. The identity of loci controlling the pod constriction trait will allow breeders to apply marker-assisted breeding approaches to shift allelic frequencies towards a slighter pod constriction and will facilitate future effort for map-based gene cloning.}, } @article {pmid30340454, year = {2018}, author = {Lopes-Marques, M and Kabeya, N and Qian, Y and Ruivo, R and Santos, MM and Venkatesh, B and Tocher, DR and Castro, LFC and Monroig, Ó}, title = {Retention of fatty acyl desaturase 1 (fads1) in Elopomorpha and Cyclostomata provides novel insights into the evolution of long-chain polyunsaturated fatty acid biosynthesis in vertebrates.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {157}, pmid = {30340454}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Fatty Acid Desaturases/chemistry/*genetics ; Fatty Acids, Unsaturated/*biosynthesis ; Fishes/*genetics/*metabolism ; Phylogeny ; Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: Provision of long-chain polyunsaturated fatty acids (LC-PUFA) in vertebrates occurs through the diet or via endogenous production from C18 precursors through consecutive elongations and desaturations. It has been postulated that the abundance of LC-PUFA in the marine environment has remarkably modulated the gene complement and function of Fads in marine teleosts. In vertebrates two fatty acyl desaturases, namely Fads1 and Fads2, encode ∆5 and ∆6 desaturases, respectively. To fully clarify the evolutionary history of LC-PUFA biosynthesis in vertebrates, we investigated the gene repertoire and function of Fads from species placed at key evolutionary nodes.

RESULTS: We demonstrate that functional Fads1Δ5 and Fads2∆6 arose from a tandem gene duplication in the ancestor of vertebrates, since they are present in the Arctic lamprey. Additionally, we show that a similar condition was retained in ray-finned fish such as the Senegal bichir and spotted gar, with the identification of fads1 genes in these lineages. Functional characterisation of the isolated desaturases reveals the first case of a Fads1 enzyme with ∆5 desaturase activity in the Teleostei lineage, the Elopomorpha. In contrast, in Osteoglossomorpha genomes, while no fads1 was identified, two separate fads2 duplicates with ∆6 and ∆5 desaturase activities respectively were uncovered.

CONCLUSIONS: We conclude that, while the essential genetic components involved LC-PUFA biosynthesis evolved in the vertebrate ancestor, the full completion of the LC-PUFA biosynthesis pathway arose uniquely in gnathostomes.}, } @article {pmid30339305, year = {2019}, author = {Santangelo, JS and Thompson, KA and Johnson, MTJ}, title = {Herbivores and plant defences affect selection on plant reproductive traits more strongly than pollinators.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {4-18}, doi = {10.1111/jeb.13392}, pmid = {30339305}, issn = {1420-9101}, support = {//National Research and Engineering Council of Canada/ ; //Ontario Graduate Scholarship/ ; //NSERC CGS-M/ ; //NSERC CGS-M/CSG-D/ ; //Queen Elizabeth II Graduate Scholarships in Science & Technology (QEII-GSST)/ ; //NSERC Discovery Grant/ ; }, abstract = {Pollinators and herbivores can both affect the evolutionary diversification of plant reproductive traits. However, plant defences frequently alter antagonistic and mutualistic interactions, and therefore, variation in plant defences may alter patterns of herbivore- and pollinator-mediated selection on plant traits. We tested this hypothesis by conducting a common garden field experiment using 50 clonal genotypes of white clover (Trifolium repens) that varied in a Mendelian-inherited chemical antiherbivore defence-the production of hydrogen cyanide (HCN). To evaluate whether plant defences alter herbivore- and/or pollinator-mediated selection, we factorially crossed chemical defence (25 cyanogenic and 25 acyanogenic genotypes), herbivore damage (herbivore suppression) and pollination (hand pollination). We found that herbivores weakened selection for increased inflorescence production, suggesting that large displays are costly in the presence of herbivores. In addition, herbivores weakened selection on flower size but only among acyanogenic plants, suggesting that plant defences reduce the strength of herbivore-mediated selection. Pollinators did not independently affect selection on any trait, although pollinators weakened selection for later flowering among cyanogenic plants. Overall, cyanogenic plant defences consistently increased the strength of positive directional selection on reproductive traits. Herbivores and pollinators both strengthened and weakened the strength of selection on reproductive traits, although herbivores imposed ~2.7× stronger selection than pollinators across all traits. Contrary to the view that pollinators are the most important agents of selection on reproductive traits, our data show that selection on reproductive traits is driven primarily by variation in herbivory and plant defences in this system.}, } @article {pmid30339293, year = {2019}, author = {van der Kooi, CJ and Ghali, K and Amptmeijer, D and Schwander, T}, title = {Niche differentiation among clones in asexual grass thrips.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {126-130}, doi = {10.1111/jeb.13393}, pmid = {30339293}, issn = {1420-9101}, support = {PP00P3_139013//Swiss National Science Foundation (SNSF)/ ; PP00P3_139013//Swiss National Science Foundation/ ; }, abstract = {Many asexual animal populations comprise a mixture of genetically different lineages, but to what degree this genetic diversity leads to ecological differences remains often unknown. Here, we test whether genetically different clonal lineages of Aptinothrips grass thrips differ in performance on a range of plants used as hosts in natural populations. We find a clear clone-by-plant species interactive effect on reproductive output, meaning that clonal lineages perform differently on different plant species and thus are characterized by disparate ecological niches. This implies that local clonal diversities can be driven and maintained by frequency-dependent selection and that resource heterogeneity can generate diverse clone assemblies.}, } @article {pmid30339119, year = {2018}, author = {Hetharua, B and Min, D and Liao, H and Lin, L and Xu, H and Tian, Y}, title = {Litorivita pollutaquae gen. nov., sp. nov., a marine bacterium in the family Rhodobacteraceae isolated from surface seawater of Xiamen Port, China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3908-3913}, doi = {10.1099/ijsem.0.003084}, pmid = {30339119}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative Rhodobacterales strain, designated as FSX-11T, was isolated from surface seawater of Xiamen port in China. Strain FSX-11T showed less than 96.5 % 16S rRNA gene sequence similarity to the type strains of species with validly published names. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the novel isolate formed a distinct monophyletic clade within the family Rhodobacteriaceae and clustered distantly with the genera Thalassobius and Marivita. Cells of strain FSX-11T were non-motile, oval-shaped and facultative anaerobic. Optimal growth occurred at 20-30 °C, at pH 7.0-8.0 and in the presence of 2-3 % NaCl (w/v). The major respiratory quinone was ubiquinone-10. Summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), 11-methyl C18 : 1ω7c and C16 : 0 were the major fatty acids. The DNA G+C content of strain FSX-11T was 58.7 mol%. On the basis of phylogenetic analysis, phenotypic and chemotaxonomic characteristics and 16S rRNA gene signature nucleotide patterns, strain FSX-11T represents a novel species in a novel genus within the family Rhodobacteraceae, for which the name Litorivita pollutaquae gen. nov., sp. nov. is proposed. The type strain is FSX-11T (=JCM 32715T=MCCC 1K03503T).}, } @article {pmid30339117, year = {2018}, author = {Efimov, BA and Chaplin, AV and Shcherbakova, VA and Suzina, NE and Podoprigora, IV and Shkoporov, AN}, title = {Prevotella rara sp. nov., isolated from human faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3818-3825}, doi = {10.1099/ijsem.0.003066}, pmid = {30339117}, issn = {1466-5034}, mesh = {Adult ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Feces/*microbiology ; Female ; Humans ; *Phylogeny ; Prevotella/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Russia ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {A strain of obligately anaerobic, Gram-stain-negative rods was isolated from human faeces and characterized both phenotypically and genotypically. Phylogenetic analysis based on 16S rRNA gene and whole-genome sequences revealed the strain to represent a member of the genus Prevotella, distant from the species with validly published names, with the closest relationship to Prevotella oryzae. The strain was moderately saccharolytic and proteolytic. The predominant menaquinones were MK-13 and MK-12. The major cellular long-chain fatty acids were anteiso-C15 : 0 and iso-C15 : 0. The genomic DNA G+C content was 45.7 mol%. On the basis of chemotaxonomic and genotypic properties, it was concluded that the strain represent a novel species within the genus Prevotella, for which the name Prevotellarara sp. nov. is proposed. The type strain of Prevotellarara is 109T (=VKM B-2992T=DSM 105141T).}, } @article {pmid30338910, year = {2018}, author = {Depaoli, MR and Hay, JC and Graier, WF and Malli, R}, title = {The enigmatic ATP supply of the endoplasmic reticulum.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12469}, pmid = {30338910}, issn = {1469-185X}, support = {I3716-B27//Austrian Science Fund/ ; P28529-B27//Austrian Science Fund/ ; //Nikon Austria/ ; }, abstract = {The endoplasmic reticulum (ER) is a functionally and morphologically complex cellular organelle largely responsible for a variety of crucial functions, including protein folding, maturation and degradation. Furthermore, the ER plays an essential role in lipid biosynthesis, dynamic Ca2+ storage, and detoxification. Malfunctions in ER-related processes are responsible for the genesis and progression of many diseases, such as heart failure, cancer, neurodegeneration and metabolic disorders. To fulfill many of its vital functions, the ER relies on a sufficient energy supply in the form of adenosine-5'-triphosphate (ATP), the main cellular energy source. Despite landmark discoveries and clarification of the functional principles of ER-resident proteins and key ER-related processes, the mechanism underlying ER ATP transport remains somewhat enigmatic. Here we summarize ER-related ATP-consuming processes and outline our knowledge about the nature and function of the ER energy supply.}, } @article {pmid30338909, year = {2018}, author = {Capobianco, A and Friedman, M}, title = {Vicariance and dispersal in southern hemisphere freshwater fish clades: a palaeontological perspective.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12473}, pmid = {30338909}, issn = {1469-185X}, support = {//Department of Earth and Environmental Sciences of the University of Michigan (Scott Turner Student Research Grant Award 2017)/ ; //Society of Systematic Biologists (2017 SSB Graduate Student Research Award)/ ; }, abstract = {Widespread fish clades that occur mainly or exclusively in fresh water represent a key target of biogeographical investigation due to limited potential for crossing marine barriers. Timescales for the origin and diversification of these groups are crucial tests of vicariant scenarios in which continental break-ups shaped modern geographic distributions. Evolutionary chronologies are commonly estimated through node-based palaeontological calibration of molecular phylogenies, but this approach ignores most of the temporal information encoded in the known fossil record of a given taxon. Here, we review the fossil record of freshwater fish clades with a distribution encompassing disjunct landmasses in the southern hemisphere. Palaeontologically derived temporal and geographic data were used to infer the plausible biogeographic processes that shaped the distribution of these clades. For seven extant clades with a relatively well-known fossil record, we used the stratigraphic distribution of their fossils to estimate confidence intervals on their times of origin. To do this, we employed a Bayesian framework that considers non-uniform preservation potential of freshwater fish fossils through time, as well as uncertainty in the absolute age of fossil horizons. We provide the following estimates for the origin times of these clades: Lepidosireniformes [125-95 million years ago (Ma)]; total-group Osteoglossomorpha (207-167 Ma); Characiformes (120-95 Ma; a younger estimate of 97-75 Ma when controversial Cenomanian fossils are excluded); Galaxiidae (235-21 Ma); Cyprinodontiformes (80-67 Ma); Channidae (79-43 Ma); Percichthyidae (127-69 Ma). These dates are mostly congruent with published molecular timetree estimates, despite the use of semi-independent data. Our reassessment of the biogeographic history of southern hemisphere freshwater fishes shows that long-distance dispersals and regional extinctions can confound and erode pre-existing vicariance-driven patterns. It is probable that disjunct distributions in many extant groups result from complex biogeographic processes that took place during the Late Cretaceous and Cenozoic. Although long-distance dispersals likely shaped the distributions of several freshwater fish clades, their exact mechanisms and their impact on broader macroevolutionary and ecological dynamics are still unclear and require further investigation.}, } @article {pmid30338027, year = {2018}, author = {Grouzdev, DS and Rysina, MS and Bryantseva, IA and Gorlenko, VM and Gaisin, VA}, title = {Draft genome sequences of 'Candidatus Chloroploca asiatica' and 'Candidatus Viridilinea mediisalina', candidate representatives of the Chloroflexales order: phylogenetic and taxonomic implications.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {24}, pmid = {30338027}, issn = {1944-3277}, abstract = {'Candidatus Chloroploca asiatica' B7-9 and 'Candidatus Viridilinea mediisalina' Kir15-3F are mesophilic filamentous anoxygenic phototrophic bacteria from alkaline aquatic environments. Both bacteria became available in the last few years and only in stable enrichment culture. In this study, we report the draft genomic sequences of 'Ca. Chloroploca asiatica' B7-9 and 'Ca. Viridilinea mediisalina' Kir15-3F, which were assembled from metagenomes of their cultures with a fold coverage 86.3× and 163.8×, respectively. The B7-9 (5.8 Mb) and the Kir15-3F (5.6 Mb) draft genome harbors 4818 and 4595 predicted protein-coding genes, respectively. In this article, we analyzed the phylogeny of representatives of the Chloroflexineae suborder in view of the appearance of new genomic data. These data were used for the revision of earlier published group-specific conserved signature indels and for searching for novel signatures for taxons in the Chloroflexineae suborder.}, } @article {pmid30338026, year = {2018}, author = {Yang, R and Liu, G and Chen, T and Zhang, W and Zhang, G and Chang, S}, title = {The complete genomic sequence of a novel cold-adapted bacterium, Planococcus maritimus Y42, isolated from crude oil-contaminated soil.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {23}, pmid = {30338026}, issn = {1944-3277}, abstract = {Planococcus maritimus Y42, isolated from the petroleum-contaminated soil of the Qaidam Basin, can use crude oil as its sole source of carbon and energy at 20 °C. The genome of P. maritimus strain Y42 has been sequenced to provide information on its properties. Genomic analysis shows that the genome of strain Y42 contains one circular DNA chromosome with a size of 3,718,896 bp and a GC content of 48.8%, and three plasmids (329,482; 89,073; and 12,282 bp). Although the strain Y42 did not show a remarkably higher ability in degrading crude oil than other oil-degrading bacteria, the existence of strain Y42 played a significant role to reducing the overall environmental impact as an indigenous oil-degrading bacterium. In addition, genome annotation revealed that strain Y42 has many genes responsible for hydrocarbon degradation. Structural features of the genomes might provide a competitive edge for P. maritimus strain Y42 to survive in oil-polluted environments and be worthy of further study in oil degradation for the recovery of crude oil-polluted environments.}, } @article {pmid30338025, year = {2018}, author = {Illikoud, N and Klopp, C and Roulet, A and Bouchez, O and Marsaud, N and Jaffrès, E and Zagorec, M}, title = {One complete and three draft genome sequences of four Brochothrix thermosphacta strains, CD 337, TAP 175, BSAS1 3 and EBP 3070.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {22}, pmid = {30338025}, issn = {1944-3277}, abstract = {Brochothrix thermosphacta is one of the dominant bacterial species associated with spoilage of chilled meat and seafood products through the production of various metabolites responsible for off-odors. However, metabolic pathways leading to meat and seafood spoilage are not all well known. The production of spoiling molecules seems to depend both on strains and on food matrix. Several B. thermosphacta genome sequences have been reported, all issued from meat isolates. Here, we report four genome sequences, one complete and three as drafts. The four B. thermosphacta strains CD 337, TAP 175, BSAS1 3, and EBP 3070 were isolated from different ecological niches (seafood or meat products either spoiled or not and bovine slaughterhouse). These strains known as phenotypically and genetically different were selected to represent intraspecies diversity. CD 337 genome is 2,594,337 bp long, complete and circular, containing 2593 protein coding sequences and 28 RNA genes. TAP 175, BSAS1 3, and EBP 3070 genomes are arranged in 57, 83, and 71 contigs, containing 2515, 2668, and 2611 protein-coding sequences, respectively. These genomes were compared with two other B. thermosphacta complete genome sequences. The main genome content differences between strains are phages, plasmids, restriction/modification systems, and cell surface functions, suggesting a similar metabolic potential but a different niche adaptation capacity.}, } @article {pmid30338024, year = {2018}, author = {Parise, D and Parise, MTD and Viana, MVC and Muñoz-Bucio, AV and Cortés-Pérez, YA and Arellano-Reynoso, B and Díaz-Aparicio, E and Dorella, FA and Pereira, FL and Carvalho, AF and Figueiredo, HCP and Ghosh, P and Barh, D and Gomide, ACP and Azevedo, VAC}, title = {First genome sequencing and comparative analyses of Corynebacterium pseudotuberculosis strains from Mexico.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {21}, pmid = {30338024}, issn = {1944-3277}, abstract = {Corynebacterium pseudotuberculosis is a pathogenic bacterium which has been rapidly spreading all over the world, causing economic losses in the agricultural sector and sporadically infecting humans. Six C. pseudotuberculosis strains were isolated from goats, sheep, and horses with distinct abscess locations. For the first time, Mexican genomes of this bacterium were sequenced and studied in silico. All strains were sequenced using Ion Personal Genome Machine sequencer, assembled using Newbler and SPAdes software. The automatic genome annotation was done using the software RAST and in-house scripts for transference, followed by manual curation using Artemis software and BLAST against NCBI and UniProt databases. The six genomes are publicly available in NCBI database. The analysis of nucleotide sequence similarity and the generated phylogenetic tree led to the observation that the Mexican strains are more similar between strains from the same host, but the genetic structure is probably more influenced by transportation of animals between farms than host preference. Also, a putative drug target was predicted and in silico analysis of 46 strains showed two gene clusters capable of differentiating the biovars equi and ovis: Restriction Modification system and CRISPR-Cas cluster.}, } @article {pmid30337711, year = {2018}, author = {Wang, Z and Yin, H and Fu, GC}, title = {Catalytic enantioconvergent coupling of secondary and tertiary electrophiles with olefins.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {379-383}, doi = {10.1038/s41586-018-0669-y}, pmid = {30337711}, issn = {1476-4687}, support = {R01 GM062871/GM/NIGMS NIH HHS/United States ; R37 GM062871/GM/NIGMS NIH HHS/United States ; }, abstract = {Carbon-carbon bonds, including those between sp3-hybridized carbon atoms (alkyl-alkyl bonds), typically comprise much of the framework of organic molecules. In the case of sp3-hybridized carbon, the carbon can be stereogenic and the particular stereochemistry can have implications for structure and function1-3. As a consequence, the development of methods that simultaneously construct alkyl-alkyl bonds and control stereochemistry is important, although challenging. Here we describe a strategy for enantioselective alkyl-alkyl bond formation, in which a racemic alkyl electrophile is coupled with an olefin in the presence of a hydrosilane, rather than via a traditional electrophile-nucleophile cross-coupling, through the action of a chiral nickel catalyst. We demonstrate that families of racemic alkyl halides-including secondary and tertiary electrophiles, which have not previously been shown to be suitable for enantioconvergent coupling with alkyl metal nucleophiles-cross-couple with olefins with good enantioselectivity and yield under very mild reaction conditions. Given the ready availability of olefins, our approach opens the door to developing more general methods for enantioconvergent alkyl-alkyl coupling.}, } @article {pmid30337485, year = {2018}, author = {Chen, M and Yan, R and Zhou, K and Li, X and Zhang, Y and Liu, C and Jiang, M and Ye, H and Meng, X and Pang, N and Zhao, L and Liu, J and Xiao, W and Hu, R and Cui, Q and Zhong, W and Zhao, Y and Zhu, M and Lin, A and Ruan, C and Dai, K}, title = {Akt-mediated platelet apoptosis and its therapeutic implications in immune thrombocytopenia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10682-E10691}, pmid = {30337485}, issn = {1091-6490}, abstract = {Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by low platelet count which can cause fatal hemorrhage. ITP patients with antiplatelet glycoprotein (GP) Ib-IX autoantibodies appear refractory to conventional treatments, and the mechanism remains elusive. Here we show that the platelets undergo apoptosis in ITP patients with anti-GPIbα autoantibodies. Consistent with these findings, the anti-GPIbα monoclonal antibodies AN51 and SZ2 induce platelet apoptosis in vitro. We demonstrate that anti-GPIbα antibody binding activates Akt, which elicits platelet apoptosis through activation of phosphodiesterase (PDE3A) and PDE3A-mediated PKA inhibition. Genetic ablation or chemical inhibition of Akt or blocking of Akt signaling abolishes anti-GPIbα antibody-induced platelet apoptosis. We further demonstrate that the antibody-bound platelets are removed in vivo through an apoptosis-dependent manner. Phosphatidylserine (PS) exposure on apoptotic platelets results in phagocytosis of platelets by macrophages in the liver. Notably, inhibition or genetic ablation of Akt or Akt-regulated apoptotic signaling or blockage of PS exposure protects the platelets from clearance. Therefore, our findings reveal pathogenic mechanisms of ITP with anti-GPIbα autoantibodies and, more importantly, suggest therapeutic strategies for thrombocytopenia caused by autoantibodies or other pathogenic factors.}, } @article {pmid30337484, year = {2018}, author = {Muchero, W and Sondreli, KL and Chen, JG and Urbanowicz, BR and Zhang, J and Singan, V and Yang, Y and Brueggeman, RS and Franco-Coronado, J and Abraham, N and Yang, JY and Moremen, KW and Weisberg, AJ and Chang, JH and Lindquist, E and Barry, K and Ranjan, P and Jawdy, S and Schmutz, J and Tuskan, GA and LeBoldus, JM}, title = {Association mapping, transcriptomics, and transient expression identify candidate genes mediating plant-pathogen interactions in a tree.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11573-11578}, pmid = {30337484}, issn = {1091-6490}, support = {P01 GM107012/GM/NIGMS NIH HHS/United States ; P41 GM103390/GM/NIGMS NIH HHS/United States ; }, abstract = {Invasive microbes causing diseases such as sudden oak death negatively affect ecosystems and economies around the world. The deployment of resistant genotypes for combating introduced diseases typically relies on breeding programs that can take decades to complete. To demonstrate how this process can be accelerated, we employed a genome-wide association mapping of ca 1,000 resequenced Populus trichocarpa trees individually challenged with Sphaerulina musiva, an invasive fungal pathogen. Among significant associations, three loci associated with resistance were identified and predicted to encode one putative membrane-bound L-type receptor-like kinase and two receptor-like proteins. A susceptibility-associated locus was predicted to encode a putative G-type D-mannose-binding receptor-like kinase. Multiple lines of evidence, including allele analysis, transcriptomics, binding assays, and overexpression, support the hypothesized function of these candidate genes in the P. trichocarpa response to S. musiva.}, } @article {pmid30337483, year = {2018}, author = {Bertzbach, LD and Laparidou, M and Härtle, S and Etches, RJ and Kaspers, B and Schusser, B and Kaufer, BB}, title = {Unraveling the role of B cells in the pathogenesis of an oncogenic avian herpesvirus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11603-11607}, pmid = {30337483}, issn = {1091-6490}, abstract = {Marek's disease virus (MDV) is a highly oncogenic alphaherpesvirus that causes immunosuppression, paralysis, and deadly lymphomas in chickens. In infected animals, B cells are efficiently infected and are thought to amplify the virus and transfer it to T cells. MDV subsequently establishes latency in T cells and transforms CD4+ T cells, resulting in fatal lymphomas. Despite many years of research, the exact role of the different B and T cell subsets in MDV pathogenesis remains poorly understood, mostly due to the lack of reverse genetics in chickens. Recently, Ig heavy chain J gene segment knockout (JH-KO) chickens lacking mature and peripheral B cells have been generated. To determine the role of these B cells in MDV pathogenesis, we infected JH-KO chickens with the very virulent MDV RB1B strain. Surprisingly, viral load in the blood of infected animals was not altered in the absence of B cells. More importantly, disease and tumor incidence in JH-KO chickens was comparable to wild-type animals, suggesting that both mature and peripheral B cells are dispensable for MDV pathogenesis. Intriguingly, MDV efficiently replicated in the bursa of Fabricius in JH-KO animals, while spread of the virus to the spleen and thymus was delayed. In the absence of B cells, MDV readily infected CD4+ and CD8+ T cells, allowing efficient virus replication in the lymphoid organs and transformation of T cells. Taken together, our data change the dogma of the central role of B cells, and thereby provide important insights into MDV pathogenesis.}, } @article {pmid30337482, year = {2018}, author = {Cooper, MA}, title = {Natural killer cells might adapt their inhibitory receptors for memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11357-11359}, pmid = {30337482}, issn = {1091-6490}, support = {R01 AI127752/AI/NIAID NIH HHS/United States ; }, } @article {pmid30337481, year = {2018}, author = {Horak, EH and Goldsmith, RH}, title = {Drumming up single-molecule beats.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11115-11117}, pmid = {30337481}, issn = {1091-6490}, mesh = {*Nanotechnology ; Physical Phenomena ; }, } @article {pmid30337480, year = {2018}, author = {Dai, WP and Zhou, D and McLaughlin, DW and Cai, D}, title = {Mechanisms underlying contrast-dependent orientation selectivity in mouse V1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11619-11624}, pmid = {30337480}, issn = {1091-6490}, abstract = {Recent experiments have shown that mouse primary visual cortex (V1) is very different from that of cat or monkey, including response properties-one of which is that contrast invariance in the orientation selectivity (OS) of the neurons' firing rates is replaced in mouse with contrast-dependent sharpening (broadening) of OS in excitatory (inhibitory) neurons. These differences indicate a different circuit design for mouse V1 than that of cat or monkey. Here we develop a large-scale computational model of an effective input layer of mouse V1. Constrained by experiment data, the model successfully reproduces experimentally observed response properties-for example, distributions of firing rates, orientation tuning widths, and response modulations of simple and complex neurons, including the contrast dependence of orientation tuning curves. Analysis of the model shows that strong feedback inhibition and strong orientation-preferential cortical excitation to the excitatory population are the predominant mechanisms underlying the contrast-sharpening of OS in excitatory neurons, while the contrast-broadening of OS in inhibitory neurons results from a strong but nonpreferential cortical excitation to these inhibitory neurons, with the resulting contrast-broadened inhibition producing a secondary enhancement on the contrast-sharpened OS of excitatory neurons. Finally, based on these mechanisms, we show that adjusting the detailed balances between the predominant mechanisms can lead to contrast invariance-providing insights for future studies on contrast dependence (invariance).}, } @article {pmid30337479, year = {2018}, author = {Brouwer, AF and Eisenberg, JNS and Pomeroy, CD and Shulman, LM and Hindiyeh, M and Manor, Y and Grotto, I and Koopman, JS and Eisenberg, MC}, title = {Epidemiology of the silent polio outbreak in Rahat, Israel, based on modeling of environmental surveillance data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {E10625-E10633}, pmid = {30337479}, issn = {1091-6490}, support = {U01 GM110712/GM/NIGMS NIH HHS/United States ; U54 GM111274/GM/NIGMS NIH HHS/United States ; }, abstract = {Israel experienced an outbreak of wild poliovirus type 1 (WPV1) in 2013-2014, detected through environmental surveillance of the sewage system. No cases of acute flaccid paralysis were reported, and the epidemic subsided after a bivalent oral polio vaccination (bOPV) campaign. As we approach global eradication, polio will increasingly be detected only through environmental surveillance. We developed a framework to convert quantitative polymerase chain reaction (qPCR) cycle threshold data into scaled WPV1 and OPV1 concentrations for inference within a deterministic, compartmental infectious disease transmission model. We used this approach to estimate the epidemic curve and transmission dynamics, as well as assess alternate vaccination scenarios. Our analysis estimates the outbreak peaked in late June, much earlier than previous estimates derived from analysis of stool samples, although the exact epidemic trajectory remains uncertain. We estimate the basic reproduction number was 1.62 (95% CI 1.04-2.02). Model estimates indicate that 59% (95% CI 9-77%) of susceptible individuals (primarily children under 10 years old) were infected with WPV1 over a little more than six months, mostly before the vaccination campaign onset, and that the vaccination campaign averted 10% (95% CI 1-24%) of WPV1 infections. As we approach global polio eradication, environmental monitoring with qPCR can be used as a highly sensitive method to enhance disease surveillance. Our analytic approach brings public health relevance to environmental data that, if systematically collected, can guide eradication efforts.}, } @article {pmid30337457, year = {2018}, author = {Martincorena, I and Fowler, JC and Wabik, A and Lawson, ARJ and Abascal, F and Hall, MWJ and Cagan, A and Murai, K and Mahbubani, K and Stratton, MR and Fitzgerald, RC and Handford, PA and Campbell, PJ and Saeb-Parsy, K and Jones, PH}, title = {Somatic mutant clones colonize the human esophagus with age.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {911-917}, doi = {10.1126/science.aau3879}, pmid = {30337457}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; MC_UU_12022/3//Medical Research Council/United Kingdom ; //Cancer Research UK/United Kingdom ; }, abstract = {The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with NOTCH1 and TP53 mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of NOTCH1 mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.}, } @article {pmid30337456, year = {2018}, author = {Guo, FS and Day, BM and Chen, YC and Tong, ML and Mansikkamäki, A and Layfield, RA}, title = {Magnetic hysteresis up to 80 kelvin in a dysprosium metallocene single-molecule magnet.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6421}, pages = {1400-1403}, doi = {10.1126/science.aav0652}, pmid = {30337456}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Single-molecule magnets (SMMs) containing only one metal center may represent the lower size limit for molecule-based magnetic information storage materials. Their current drawback is that all SMMs require liquid-helium cooling to show magnetic memory effects. We now report a chemical strategy to access the dysprosium metallocene cation [(Cp i Pr5)Dy(Cp*)]+ (Cp i Pr5, penta-iso-propylcyclopentadienyl; Cp*, pentamethylcyclopentadienyl), which displays magnetic hysteresis above liquid-nitrogen temperatures. An effective energy barrier to reversal of the magnetization of Ueff = 1541 wave number is also measured. The magnetic blocking temperature of TB = 80 kelvin for this cation overcomes an essential barrier toward the development of nanomagnet devices that function at practical temperatures.}, } @article {pmid30337455, year = {2018}, author = {Harrington, LB and Burstein, D and Chen, JS and Paez-Espino, D and Ma, E and Witte, IP and Cofsky, JC and Kyrpides, NC and Banfield, JF and Doudna, JA}, title = {Programmed DNA destruction by miniature CRISPR-Cas14 enzymes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {839-842}, doi = {10.1126/science.aav4294}, pmid = {30337455}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {CRISPR-Cas systems provide microbes with adaptive immunity to infectious nucleic acids and are widely employed as genome editing tools. These tools use RNA-guided Cas proteins whose large size (950 to 1400 amino acids) has been considered essential to their specific DNA- or RNA-targeting activities. Here we present a set of CRISPR-Cas systems from uncultivated archaea that contain Cas14, a family of exceptionally compact RNA-guided nucleases (400 to 700 amino acids). Despite their small size, Cas14 proteins are capable of targeted single-stranded DNA (ssDNA) cleavage without restrictive sequence requirements. Moreover, target recognition by Cas14 triggers nonspecific cutting of ssDNA molecules, an activity that enables high-fidelity single-nucleotide polymorphism genotyping (Cas14-DETECTR). Metagenomic data show that multiple CRISPR-Cas14 systems evolved independently and suggest a potential evolutionary origin of single-effector CRISPR-based adaptive immunity.}, } @article {pmid30337454, year = {2018}, author = {Jin, S and Huang, M and Kwon, Y and Zhang, L and Li, BW and Oh, S and Dong, J and Luo, D and Biswal, M and Cunning, BV and Bakharev, PV and Moon, I and Yoo, WJ and Camacho-Mojica, DC and Kim, YJ and Lee, SH and Wang, B and Seong, WK and Saxena, M and Ding, F and Shin, HJ and Ruoff, RS}, title = {Colossal grain growth yields single-crystal metal foils by contact-free annealing.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {1021-1025}, doi = {10.1126/science.aao3373}, pmid = {30337454}, issn = {1095-9203}, abstract = {Single-crystal metals have distinctive properties owing to the absence of grain boundaries and strong anisotropy. Commercial single-crystal metals are usually synthesized by bulk crystal growth or by deposition of thin films onto substrates, and they are expensive and small. We prepared extremely large single-crystal metal foils by "contact-free annealing" from commercial polycrystalline foils. The colossal grain growth (up to 32 square centimeters) is achieved by minimizing contact stresses, resulting in a preferred in-plane and out-of-plane crystal orientation, and is driven by surface energy minimization during the rotation of the crystal lattice followed by "consumption" of neighboring grains. Industrial-scale production of single-crystal metal foils is possible as a result of this discovery.}, } @article {pmid30337412, year = {2018}, author = {Lee, JM}, title = {Leaving my comfort zone.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {370}, doi = {10.1126/science.362.6412.370}, pmid = {30337412}, issn = {1095-9203}, } @article {pmid30337411, year = {2018}, author = {Del Fresno, C and Saz-Leal, P and Enamorado, M and Wculek, SK and Martínez-Cano, S and Blanco-Menéndez, N and Schulz, O and Gallizioli, M and Miró-Mur, F and Cano, E and Planas, A and Sancho, D}, title = {DNGR-1 in dendritic cells limits tissue damage by dampening neutrophil recruitment.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {351-356}, doi = {10.1126/science.aan8423}, pmid = {30337411}, issn = {1095-9203}, mesh = {Animals ; Candida albicans/*immunology ; Candidiasis/*pathology ; Dendritic Cells/*immunology ; Lectins, C-Type/genetics/*physiology ; Mice ; Mice, Mutant Strains ; Necrosis ; Neutrophil Infiltration/genetics/*immunology ; Pancreas/immunology/microbiology/*pathology ; Pancreatitis, Acute Necrotizing/microbiology/*pathology ; Receptors, Immunologic/genetics/*physiology ; }, abstract = {Host injury triggers feedback mechanisms that limit tissue damage. Conventional type 1 dendritic cells (cDC1s) express dendritic cell natural killer lectin group receptor-1 (DNGR-1), encoded by the gene Clec9a, which senses tissue damage and favors cross-presentation of dead-cell material to CD8+ T cells. Here we find that DNGR-1 additionally reduces host-damaging inflammatory responses induced by sterile and infectious tissue injury in mice. DNGR-1 deficiency leads to exacerbated caerulein-induced necrotizing pancreatitis and increased pathology during systemic Candida albicans infection without affecting fungal burden. This effect is B and T cell-independent and attributable to increased neutrophilia in DNGR-1-deficient settings. Mechanistically, DNGR-1 engagement activates SHP-1 and inhibits MIP-2 (encoded by Cxcl2) production by cDC1s during Candida infection. This consequently restrains neutrophil recruitment and promotes disease tolerance. Thus, DNGR-1-mediated sensing of injury by cDC1s serves as a rheostat for the control of tissue damage, innate immunity, and immunopathology.}, } @article {pmid30337410, year = {2018}, author = {Hie, B and Cho, H and Berger, B}, title = {Realizing private and practical pharmacological collaboration.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {347-350}, doi = {10.1126/science.aat4807}, pmid = {30337410}, issn = {1095-9203}, support = {R01 GM081871/GM/NIGMS NIH HHS/United States ; }, mesh = {Computer Simulation ; *Confidentiality ; Databases, Pharmaceutical/*legislation & jurisprudence ; *Drug Delivery Systems ; Humans ; Information Dissemination/*legislation & jurisprudence/*methods ; Pharmacology/*legislation & jurisprudence ; }, abstract = {Although combining data from multiple entities could power life-saving breakthroughs, open sharing of pharmacological data is generally not viable because of data privacy and intellectual property concerns. To this end, we leverage modern cryptographic tools to introduce a computational protocol for securely training a predictive model of drug-target interactions (DTIs) on a pooled dataset that overcomes barriers to data sharing by provably ensuring the confidentiality of all underlying drugs, targets, and observed interactions. Our protocol runs within days on a real dataset of more than 1 million interactions and is more accurate than state-of-the-art DTI prediction methods. Using our protocol, we discover previously unidentified DTIs that we experimentally validated via targeted assays. Our work lays a foundation for more effective and cooperative biomedical research.}, } @article {pmid30337409, year = {2018}, author = {Shellard, A and Szabó, A and Trepat, X and Mayor, R}, title = {Supracellular contraction at the rear of neural crest cell groups drives collective chemotaxis.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {339-343}, pmid = {30337409}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; //Medical Research Council/United Kingdom ; //European Research Council/International ; }, mesh = {Actomyosin/*physiology ; Animals ; Chemokine CXCL12 ; *Chemotaxis ; Embryonic Stem Cells/*physiology ; Neural Crest/*cytology ; Neural Stem Cells/*physiology ; Optogenetics ; Xenopus ; Zebrafish ; Zebrafish Proteins ; }, abstract = {Collective cell chemotaxis, the directed migration of cell groups along gradients of soluble chemical cues, underlies various developmental and pathological processes. We use neural crest cells, a migratory embryonic stem cell population whose behavior has been likened to malignant invasion, to study collective chemotaxis in vivo. Studying Xenopus and zebrafish, we have shown that the neural crest exhibits a tensile actomyosin ring at the edge of the migratory cell group that contracts in a supracellular fashion. This contractility is polarized during collective cell chemotaxis: It is inhibited at the front but persists at the rear of the cell cluster. The differential contractility drives directed collective cell migration ex vivo and in vivo through the intercalation of rear cells. Thus, in neural crest cells, collective chemotaxis works by rear-wheel drive.}, } @article {pmid30337408, year = {2018}, author = {Willke, P and Bae, Y and Yang, K and Lado, JL and Ferrón, A and Choi, T and Ardavan, A and Fernández-Rossier, J and Heinrich, AJ and Lutz, CP}, title = {Hyperfine interaction of individual atoms on a surface.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {336-339}, doi = {10.1126/science.aat7047}, pmid = {30337408}, issn = {1095-9203}, abstract = {Taking advantage of nuclear spins for electronic structure analysis, magnetic resonance imaging, and quantum devices hinges on knowledge and control of the surrounding atomic-scale environment. We measured and manipulated the hyperfine interaction of individual iron and titanium atoms placed on a magnesium oxide surface by using spin-polarized scanning tunneling microscopy in combination with single-atom electron spin resonance. Using atom manipulation to move single atoms, we found that the hyperfine interaction strongly depended on the binding configuration of the atom. We could extract atom- and position-dependent information about the electronic ground state, the state mixing with neighboring atoms, and properties of the nuclear spin. Thus, the hyperfine spectrum becomes a powerful probe of the chemical environment of individual atoms and nanostructures.}, } @article {pmid30337407, year = {2018}, author = {Tkalčić, H and Phạm, TS}, title = {Shear properties of Earth's inner core constrained by a detection of J waves in global correlation wavefield.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {329-332}, doi = {10.1126/science.aau7649}, pmid = {30337407}, issn = {1095-9203}, abstract = {Seismic J waves, shear waves that traverse Earth's inner core, provide direct constraints on the inner core's solidity and shear properties. However, these waves have been elusive in the direct seismic wavefield because of their small amplitudes. We devised a new method to detect J waves in the earthquake coda correlation wavefield. They manifest through the similarity with other compressional core-sensitive signals. The inner core is solid, but relatively soft, with shear-wave speeds and shear moduli of 3.42 ± 0.02 kilometers per second and 149.0 ± 1.6 gigapascals (GPa) near the inner core boundary and 3.58 ± 0.02 kilometers per second and 167.4 ± 1.6 GPa in Earth's center. The values are 2.5% lower than the widely used Preliminary Earth Reference Model. This provides new constraints on the dynamical interpretation of Earth's inner core.}, } @article {pmid30337406, year = {2018}, author = {Nam, Y and Ki, DK and Soler-Delgado, D and Morpurgo, AF}, title = {A family of finite-temperature electronic phase transitions in graphene multilayers.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {324-328}, doi = {10.1126/science.aar6855}, pmid = {30337406}, issn = {1095-9203}, support = {//Swiss National Science Foundation/Switzerland ; }, abstract = {Suspended Bernal-stacked graphene multilayers up to an unexpectedly large thickness exhibit a broken-symmetry ground state whose origin remains to be understood. We show that a finite-temperature second-order phase transition occurs in multilayers whose critical temperature (Tc) increases from 12 kelvins (K) in bilayers to 100 K in heptalayers. A comparison of the data with a phenomenological model inspired by a mean-field approach suggests that the transition is associated with the appearance of a self-consistent valley- and spin-dependent staggered potential that changes sign from one layer to the next, appearing at Tc and increasing upon cooling. The systematic evolution with thickness of several measured quantities imposes constraints on any microscopic theory aiming to analyze the nature of electronic correlations in this system.}, } @article {pmid30337405, year = {2018}, author = {Kitanosono, T and Xu, P and Kobayashi, S}, title = {Chiral Lewis acids integrated with single-walled carbon nanotubes for asymmetric catalysis in water.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {311-315}, doi = {10.1126/science.aap7883}, pmid = {30337405}, issn = {1095-9203}, abstract = {The development of highly reactive and stereoselective catalytic systems is required not only to improve existing synthetic methods but also to invent distinct chemical reactions. Herein, a homogenized combination of nickel-based Lewis acid-surfactant-combined catalysts and single-walled carbon nanotubes is shown to exhibit substantial activity in water. In addition to the enhanced reactivity, stereoselective performance and long-term stability were demonstrated in asymmetric conjugate addition reactions of aldoximes to furnish chiral nitrones in high yields with excellent selectivities. The practical and straightforward application of the designed catalysts in water provides an expedient, environmentally benign, and highly efficient pathway to access optically active compounds.}, } @article {pmid30337404, year = {2018}, author = {Bravyi, S and Gosset, D and König, R}, title = {Quantum advantage with shallow circuits.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {308-311}, doi = {10.1126/science.aar3106}, pmid = {30337404}, issn = {1095-9203}, abstract = {Quantum effects can enhance information-processing capabilities and speed up the solution of certain computational problems. Whether a quantum advantage can be rigorously proven in some setting or demonstrated experimentally using near-term devices is the subject of active debate. We show that parallel quantum algorithms running in a constant time period are strictly more powerful than their classical counterparts; they are provably better at solving certain linear algebra problems associated with binary quadratic forms. Our work gives an unconditional proof of a computational quantum advantage and simultaneously pinpoints its origin: It is a consequence of quantum nonlocality. The proposed quantum algorithm is a suitable candidate for near-future experimental realizations, as it requires only constant-depth quantum circuits with nearest-neighbor gates on a two-dimensional grid of qubits (quantum bits).}, } @article {pmid30337403, year = {2018}, author = {Zhou, Y and Liu, Y}, title = {China's fight against soil pollution.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {298}, doi = {10.1126/science.aav4061}, pmid = {30337403}, issn = {1095-9203}, mesh = {China ; *Conservation of Natural Resources ; Environmental Pollution/*prevention & control ; Human Activities ; Humans ; }, } @article {pmid30337402, year = {2018}, author = {Eisthen, HL and Halanych, KM and Kelley, DB and White, SA and Phelps, SM and , }, title = {New NSF policy will stifle innovation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {297-298}, doi = {10.1126/science.aav4793}, pmid = {30337402}, issn = {1095-9203}, mesh = {Biomedical Research/*economics ; Foundations ; Policy ; United States ; }, } @article {pmid30337401, year = {2018}, author = {Park, A}, title = {Ethics and politics of conservation triage.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {297}, doi = {10.1126/science.aav4382}, pmid = {30337401}, issn = {1095-9203}, mesh = {Ethics, Medical ; *Politics ; *Triage ; }, } @article {pmid30337400, year = {2018}, author = {Irving, JCE}, title = {Earth's soft heart.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {294}, doi = {10.1126/science.aav2296}, pmid = {30337400}, issn = {1095-9203}, mesh = {*Earth (Planet) ; *Heart ; }, } @article {pmid30337399, year = {2018}, author = {Salazar, F and Brown, GD}, title = {A friendly danger.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {292-293}, doi = {10.1126/science.aav3477}, pmid = {30337399}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; //Medical Research Council/United Kingdom ; //Arthritis Research UK/United Kingdom ; }, } @article {pmid30337398, year = {2018}, author = {Gill, ME and Peters, AHFM}, title = {Toward human egg-like cells in vitro.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {291-292}, doi = {10.1126/science.aav3479}, pmid = {30337398}, issn = {1095-9203}, mesh = {Humans ; *Ovum ; }, } @article {pmid30337397, year = {2018}, author = {Adameyko, I}, title = {Supracellular contractions propel migration.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {290-291}, doi = {10.1126/science.aav3376}, pmid = {30337397}, issn = {1095-9203}, } @article {pmid30337396, year = {2018}, author = {Montanaro, A}, title = {Computational complexity, step by step.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {289}, doi = {10.1126/science.aau9555}, pmid = {30337396}, issn = {1095-9203}, mesh = {*Algorithms ; *Computational Biology ; }, } @article {pmid30337395, year = {2018}, author = {Graham, C and Laffan, K and Pinto, S}, title = {Well-being in metrics and policy.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {287-288}, doi = {10.1126/science.aau5234}, pmid = {30337395}, issn = {1095-9203}, mesh = {African Americans/psychology ; *Economic Development ; European Continental Ancestry Group/psychology ; Female ; Gross Domestic Product ; *Happiness ; Hispanic Americans/psychology ; Humans ; *Life Expectancy ; Male ; *Personal Satisfaction ; Policy Making ; }, } @article {pmid30337394, year = {2018}, author = {Gerber, LR and Runge, MC and Maloney, RF and Iacona, GD and Drew, CA and Avery-Gomm, S and Brazill-Boast, J and Crouse, D and Epanchin-Niell, RS and Hall, SB and Maguire, LA and Male, T and Morgan, D and Newman, J and Possingham, HP and Rumpff, L and Weiss, KCB and Wilson, RS and Zablan, MA}, title = {Endangered species recovery: A resource allocation problem.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {284-286}, doi = {10.1126/science.aat8434}, pmid = {30337394}, issn = {1095-9203}, mesh = {Animals ; Endangered Species/*legislation & jurisprudence ; Environmental Policy/*legislation & jurisprudence ; United States ; }, } @article {pmid30337393, year = {2018}, author = {Couzin-Frankel, J}, title = {Toxin or treatment?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {278-282}, doi = {10.1126/science.362.6412.278}, pmid = {30337393}, issn = {1095-9203}, mesh = {Anxiety ; Arachis/*adverse effects ; Child ; Desensitization, Immunologic/adverse effects/*methods/psychology ; Humans ; Immunotherapy/*methods ; Male ; Peanut Hypersensitivity/*therapy ; Risk ; }, } @article {pmid30337392, year = {2018}, author = {Vogel, G}, title = {Outbreaks of poliolike disease pose a puzzle.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {277}, doi = {10.1126/science.362.6412.277}, pmid = {30337392}, issn = {1095-9203}, mesh = {*Disease Outbreaks ; *Enterovirus ; Enterovirus Infections/*epidemiology ; Humans ; Myelitis/*epidemiology/*virology ; Paralysis/*epidemiology/*virology ; United States/epidemiology ; }, } @article {pmid30337391, year = {2018}, author = {Normile, D}, title = {China narrows U.S. lead in R&D spending.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {276}, doi = {10.1126/science.362.6412.276}, pmid = {30337391}, issn = {1095-9203}, } @article {pmid30337390, year = {2018}, author = {Voosen, P}, title = {NASA's asteroid explorer Dawn soon to go dark.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {275}, doi = {10.1126/science.362.6412.275}, pmid = {30337390}, issn = {1095-9203}, } @article {pmid30337389, year = {2018}, author = {Clery, D}, title = {Planet hunter nears its end.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {274-275}, doi = {10.1126/science.362.6412.274}, pmid = {30337389}, issn = {1095-9203}, } @article {pmid30337388, year = {2018}, author = {Escobar, H}, title = {Scientists, environmentalists brace for Brazil's right turn.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {273-274}, doi = {10.1126/science.362.6412.273}, pmid = {30337388}, issn = {1095-9203}, mesh = {*Biodiversity ; Brazil ; Climate Change/*economics ; *Investments ; *Politics ; }, } @article {pmid30337387, year = {2018}, author = {Mervis, J}, title = {Scientists who beat the odds seek victory in November.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {271-273}, doi = {10.1126/science.362.6412.271}, pmid = {30337387}, issn = {1095-9203}, } @article {pmid30337386, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {268-270}, doi = {10.1126/science.362.6412.268}, pmid = {30337386}, issn = {1095-9203}, } @article {pmid30337385, year = {2018}, author = {Le Duc, JW and Yuan, Z}, title = {Network for safe and secure labs.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {267}, doi = {10.1126/science.aav7120}, pmid = {30337385}, issn = {1095-9203}, mesh = {China ; Containment of Biohazards/*methods ; Disease Outbreaks/*prevention & control ; Laboratories/*organization & administration ; United States ; }, } @article {pmid30337384, year = {2018}, author = {Falk, A and Hermle, J}, title = {Relationship of gender differences in preferences to economic development and gender equality.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {}, doi = {10.1126/science.aas9899}, pmid = {30337384}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {*Economic Development ; *Economics, Behavioral ; Female ; Humans ; Male ; Sex Factors ; *Social Desirability ; }, abstract = {Preferences concerning time, risk, and social interactions systematically shape human behavior and contribute to differential economic and social outcomes between women and men. We present a global investigation of gender differences in six fundamental preferences. Our data consist of measures of willingness to take risks, patience, altruism, positive and negative reciprocity, and trust for 80,000 individuals in 76 representative country samples. Gender differences in preferences were positively related to economic development and gender equality. This finding suggests that greater availability of and gender-equal access to material and social resources favor the manifestation of gender-differentiated preferences across countries.}, } @article {pmid30337383, year = {2018}, author = {Wehner, S and Elkouss, D and Hanson, R}, title = {Quantum internet: A vision for the road ahead.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {}, doi = {10.1126/science.aam9288}, pmid = {30337383}, issn = {1095-9203}, abstract = {The internet-a vast network that enables simultaneous long-range classical communication-has had a revolutionary impact on our world. The vision of a quantum internet is to fundamentally enhance internet technology by enabling quantum communication between any two points on Earth. Such a quantum internet may operate in parallel to the internet that we have today and connect quantum processors in order to achieve capabilities that are provably impossible by using only classical means. Here, we propose stages of development toward a full-blown quantum internet and highlight experimental and theoretical progress needed to attain them.}, } @article {pmid30337382, year = {2018}, author = {}, title = {Erratum for the Research Article "Recombination initiation maps of individual human genomes" by F. Pratto, K. Brick, P. Khil, F. Smagulova, G. V. Petukhova, R. D. Camerini-Otero.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {}, doi = {10.1126/science.aav6294}, pmid = {30337382}, issn = {1095-9203}, } @article {pmid30337381, year = {2018}, author = {Kremen, C and Merenlender, AM}, title = {Landscapes that work for biodiversity and people.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {}, doi = {10.1126/science.aau6020}, pmid = {30337381}, issn = {1095-9203}, mesh = {Agriculture ; *Biodiversity ; Climate Change ; *Conservation of Natural Resources ; Forestry ; Forests ; Humans ; }, abstract = {How can we manage farmlands, forests, and rangelands to respond to the triple challenge of the Anthropocene-biodiversity loss, climate change, and unsustainable land use? When managed by using biodiversity-based techniques such as agroforestry, silvopasture, diversified farming, and ecosystem-based forest management, these socioeconomic systems can help maintain biodiversity and provide habitat connectivity, thereby complementing protected areas and providing greater resilience to climate change. Simultaneously, the use of these management techniques can improve yields and profitability more sustainably, enhancing livelihoods and food security. This approach to "working lands conservation" can create landscapes that work for nature and people. However, many socioeconomic challenges impede the uptake of biodiversity-based land management practices. Although improving voluntary incentives, market instruments, environmental regulations, and governance is essential to support working lands conservation, it is community action, social movements, and broad coalitions among citizens, businesses, nonprofits, and government agencies that have the power to transform how we manage land and protect the environment.}, } @article {pmid30337380, year = {2018}, author = {Barbi, E and Lagona, F and Marsili, M and Vaupel, JW and Wachter, KW}, title = {Response to Comment on "The plateau of human mortality: Demography of longevity pioneers".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {}, doi = {10.1126/science.aav3229}, pmid = {30337380}, issn = {1095-9203}, mesh = {*Demography ; Humans ; Life Expectancy ; *Longevity ; Mortality ; Population Dynamics ; }, abstract = {Beltrán-Sánchez et al based their comment on misleading calculations of the maximum survival age. With realistic numbers of people attaining age 105 and the estimated plateau, the Jeanne Calment record is indeed plausible.}, } @article {pmid30337139, year = {2018}, author = {Lowe, JWE}, title = {Sequencing through thick and thin: Historiographical and philosophical implications.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {72}, number = {}, pages = {10-27}, doi = {10.1016/j.shpsc.2018.10.007}, pmid = {30337139}, issn = {1879-2499}, mesh = {Animals ; *Genome ; Genomics/*history ; *Historiography ; History, 21st Century ; *Philosophy ; Sequence Analysis, DNA/history/*veterinary ; Sus scrofa/*genetics ; }, abstract = {DNA sequencing has been characterised by scholars and life scientists as an example of 'big', 'fast' and 'automated' science in biology. This paper argues, however, that these characterisations are a product of a particular interpretation of what sequencing is, what I call 'thin sequencing'. The 'thin sequencing' perspective focuses on the determination of the order of bases in a particular stretch of DNA. Based upon my research on the pig genome mapping and sequencing projects, I provide an alternative 'thick sequencing' perspective, which also includes a number of practices that enable the sequence to travel across and be used in wider communities. If we take sequencing in the thin manner to be an event demarcated by the determination of sequences in automated sequencing machines and computers, this has consequences for the historical analysis of sequencing projects, as it focuses attention on those parts of the work of sequencing that are more centralised, fast (and accelerating) and automated. I argue instead that sequencing can be interpreted as a more open-ended process including activities such as the generation of a minimum tile path or annotation, and detail the historiographical and philosophical consequences of this move.}, } @article {pmid30336972, year = {2018}, author = {Chen, S and Bonifati, S and Qin, Z and St Gelais, C and Wu, L}, title = {SAMHD1 Suppression of Antiviral Immune Responses.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.09.009}, pmid = {30336972}, issn = {1878-4380}, support = {R01 AI104483/AI/NIAID NIH HHS/United States ; R01 AI120209/AI/NIAID NIH HHS/United States ; R01 GM128212/GM/NIGMS NIH HHS/United States ; }, abstract = {SAMHD1 is a host triphosphohydrolase that degrades intracellular deoxynucleoside triphosphates (dNTPs) to a lower level that restricts viral DNA synthesis, and thus prevents replication of diverse viruses in nondividing cells. Recent progress indicates that SAMHD1 negatively regulates antiviral innate immune responses and inflammation through interacting with various key proteins in immune signaling and DNA damage-repair pathways. SAMHD1 can also modulate antibody production in adaptive immune responses. In this review, we summarize how SAMHD1 regulates antiviral immune responses through distinct mechanisms, and discuss the implications of these new functions of SAMHD1. Furthermore, we propose important new questions and future directions that can advance functional and mechanistic studies of SAMHD1-mediated immune regulation during viral infections.}, } @article {pmid30336790, year = {2018}, author = {Liu, YR and Delgado-Baquerizo, M and Bi, L and Zhu, J and He, JZ}, title = {Consistent responses of soil microbial taxonomic and functional attributes to mercury pollution across China.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {183}, pmid = {30336790}, issn = {2049-2618}, abstract = {BACKGROUND: The ecological consequences of mercury (Hg) pollution-one of the major pollutants worldwide-on microbial taxonomic and functional attributes remain poorly understood and largely unexplored. Using soils from two typical Hg-impacted regions across China, here, we evaluated the role of Hg pollution in regulating bacterial abundance, diversity, and co-occurrence network. We also investigated the associations between Hg contents and the relative abundance of microbial functional genes by analyzing the soil metagenomes from a subset of those sites.

RESULTS: We found that soil Hg largely influenced the taxonomic and functional attributes of microbial communities in the two studied regions. In general, Hg pollution was negatively related to bacterial abundance, but positively related to the diversity of bacteria in two separate regions. We also found some consistent associations between soil Hg contents and the community composition of bacteria. For example, soil total Hg content was positively related to the relative abundance of Firmicutes and Bacteroidetes in both paddy and upland soils. In contrast, the methylmercury (MeHg) concentration was negatively correlated to the relative abundance of Nitrospirae in the two types of soils. Increases in soil Hg pollution correlated with drastic changes in the relative abundance of ecological clusters within the co-occurrence network of bacterial communities for the two regions. Using metagenomic data, we were also able to detect the effect of Hg pollution on multiple functional genes relevant to key soil processes such as element cycles and Hg transformations (e.g., methylation and reduction).

CONCLUSIONS: Together, our study provides solid evidence that Hg pollution has predictable and significant effects on multiple taxonomic and functional attributes including bacterial abundance, diversity, and the relative abundance of ecological clusters and functional genes. Our results suggest an increase in soil Hg pollution linked to human activities will lead to predictable shifts in the taxonomic and functional attributes in the Hg-impacted areas, with potential implications for sustainable management of agricultural ecosystems and elsewhere.}, } @article {pmid30336787, year = {2018}, author = {Hu, M and Li, J and Chen, R and Li, W and Feng, L and Shi, L and Xue, Y and Feng, X and Zhang, L and Zhou, J}, title = {Dickeya zeae strains isolated from rice, banana and clivia rot plants show great virulence differentials.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {136}, pmid = {30336787}, issn = {1471-2180}, support = {2015CB150600//National Key Project for Basic Research of China (973 Program)/ ; 2017A010105009//Science and Technology Planning Project of Guangdong Province, China/ ; 2016KZDXM026//Guangdong Province "Innovation and University Development" Project/ ; }, abstract = {BACKGROUND: Dickeya zeae is the causal agent of maize and rice foot rot diseases, but recently it was also found to infect banana and cause severe losses in China. Strains from different sources showed significant diversity in nature, implying complicated evolution history and pathogenic mechanisms.

RESULTS: D. zeae strains were isolated from soft rot banana plants and ornamental monocotyledonous Clivia miniata. Compared with D. zeae strain EC1 isolated from rice, clivia isolates did not show any antimicrobial activity, produced less extracellular enzymes, had a much narrow host ranges, but released higher amount of extracellular polysaccharides (EPS). In contrast, the banana isolates in general produced more extracellular enzymes and EPS than strain EC1. Furthermore, we provided evidence that the banana D. zeae isolate MS2 produces a new antibiotic/phytotoxin(s), which differs from the zeamine toxins produced by rice pathogen D. zeae strain EC1 genetically and in its antimicrobial potency.

CONCLUSIONS: The findings from this study expanded the natural host range of D. zeae and highlighted the genetic and phenotypic divergence of D. zeae strains. Conclusions can be drawn from a series of tests that at least two types of D. zeae strains could cause the soft rot disease of banana, with one producing antimicrobial compound while the other producing none, and the D. zeae clivia strains could only infect monocot hosts. D. zeae strains isolated from different sources have diverse virulence characteristics.}, } @article {pmid30336777, year = {2018}, author = {Li, P and Xue, Y and Shi, J and Pan, A and Tang, X and Ming, F}, title = {The response of dominant and rare taxa for fungal diversity within different root environments to the cultivation of Bt and conventional cotton varieties.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {184}, pmid = {30336777}, issn = {2049-2618}, abstract = {BACKGROUND: Bacillus thuringiensis (Bt) crops have been cultivated at a large scale over the past several decades, which have raised concern about unintended effects on natural environments. Microbial communities typically contain numerous rare taxa that make up the majority of community populations. However, the response of dominant and rare taxa for fungal diversity to the different root environments of Bt plants remains unclear.

RESULTS: We quantified fungal population sizes and community composition via quantitative PCR of ITS genes and 18S rRNA gene sequencing of, respectively, that were associated with Bt and conventional cotton variety rhizosphere soils from different plant growth stages. qPCR analyses indicated that fungal abundances reached their peak at the seedling stage and that the taproots and lateral root rhizospheres of the Bt cotton SGK321 were significantly different. However, no significant differences in population sizes were detected between the same root zones from Bt and the conventional cotton varieties. The overall patterns of fungal genera abundances followed that of the dominant genera, whereas overall patterns of fungal genera richness followed those of the rare genera. These results suggest that the dominant and rare taxa play different roles in the maintenance of rhizosphere microhabitat ecosystems. Cluster analyses indicated a separation of fungal communities based on the lateral roots or taproots from the three cotton varieties at the seedling stage, suggesting that root microhabitats had marked effects on fungal community composition. Redundancy analyses indicated that pH was more correlated to soil fungal community composition than Bt protein content.

CONCLUSIONS: In conclusion, these results indicate that dominant and rare fungal taxa differentially contribute to community dynamics in different root microhabitats of both Bt and conventional cotton varieties. Moreover, these results showed that the rhizosphere fungal community of Bt cotton did not respond significantly to the presence of Bt protein when compared to the two conventional cotton varieties.}, } @article {pmid30336775, year = {2018}, author = {Roguet, A and Eren, AM and Newton, RJ and McLellan, SL}, title = {Fecal source identification using random forest.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {185}, pmid = {30336775}, issn = {2049-2618}, support = {R01 AI091829/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Clostridiales and Bacteroidales are uniquely adapted to the gut environment and have co-evolved with their hosts resulting in convergent microbiome patterns within mammalian species. As a result, members of Clostridiales and Bacteroidales are particularly suitable for identifying sources of fecal contamination in environmental samples. However, a comprehensive evaluation of their predictive power and development of computational approaches is lacking. Given the global public health concern for waterborne disease, accurate identification of fecal pollution sources is essential for effective risk assessment and management. Here, we use random forest algorithm and 16S rRNA gene amplicon sequences assigned to Clostridiales and Bacteroidales to identify common fecal pollution sources. We benchmarked the accuracy, consistency, and sensitivity of our classification approach using fecal, environmental, and artificial in silico generated samples.

RESULTS: Clostridiales and Bacteroidales classifiers were composed mainly of sequences that displayed differential distributions (host-preferred) among sewage, cow, deer, pig, cat, and dog sources. Each classifier correctly identified human and individual animal sources in approximately 90% of the fecal and environmental samples tested. Misclassifications resulted mostly from false-positive identification of cat and dog fecal signatures in host animals not used to build the classifiers, suggesting characterization of additional animals would improve accuracy. Random forest predictions were highly reproducible, reflecting the consistency of the bacterial signatures within each of the animal and sewage sources. Using in silico generated samples, we could detect fecal bacterial signatures when the source dataset accounted for as little as ~ 0.5% of the assemblage, with ~ 0.04% of the sequences matching the classifiers. Finally, we developed a proxy to estimate proportions among sources, which allowed us to determine which sources contribute the most to observed fecal pollution.

CONCLUSION: Random forest classification with 16S rRNA gene amplicons offers a rapid, sensitive, and accurate solution for identifying host microbial signatures to detect human and animal fecal contamination in environmental samples.}, } @article {pmid30336771, year = {2018}, author = {van Dijk, J and Bompard, G and Cau, J and Kunishima, S and Rabeharivelo, G and Mateos-Langerak, J and Cazevieille, C and Cavelier, P and Boizet-Bonhoure, B and Delsert, C and Morin, N}, title = {Microtubule polyglutamylation and acetylation drive microtubule dynamics critical for platelet formation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {116}, pmid = {30336771}, issn = {1741-7007}, abstract = {BACKGROUND: Upon maturation in the bone marrow, polyploid megakaryocytes elongate very long and thin cytoplasmic branches called proplatelets. Proplatelets enter the sinusoids blood vessels in which platelets are ultimately released. Microtubule dynamics, bundling, sliding, and coiling, drive these dramatic morphological changes whose regulation remains poorly understood. Microtubule properties are defined by tubulin isotype composition and post-translational modification patterns. It remains unknown whether microtubule post-translational modifications occur in proplatelets and if so, whether they contribute to platelet formation.

RESULTS: Here, we show that in proplatelets from mouse megakaryocytes, microtubules are both acetylated and polyglutamylated. To bypass the difficulties of working with differentiating megakaryocytes, we used a cell model that allowed us to test the functions of these modifications. First, we show that α2bβ3integrin signaling in D723H cells is sufficient to induce β1tubulin expression and recapitulate the specific microtubule behaviors observed during proplatelet elongation and platelet release. Using this model, we found that microtubule acetylation and polyglutamylation occur with different spatio-temporal patterns. We demonstrate that microtubule acetylation, polyglutamylation, and β1tubulin expression are mandatory for proplatelet-like elongation, swelling formation, and cytoplast severing. We discuss the functional importance of polyglutamylation of β1tubulin-containing microtubules for their efficient bundling and coiling during platelet formation.

CONCLUSIONS: We characterized and validated a powerful cell model to address microtubule behavior in mature megakaryocytes, which allowed us to demonstrate the functional importance of microtubule acetylation and polyglutamylation for platelet release. Furthermore, we bring evidence of a link between the expression of a specific tubulin isotype, the occurrence of microtubule post-translational modifications, and the acquisition of specific microtubule behaviors. Thus, our findings could widen the current view of the regulation of microtubule behavior in cells such as osteoclasts, spermatozoa, and neurons, which express distinct tubulin isotypes and display specific microtubule activities during differentiation.}, } @article {pmid30336217, year = {2019}, author = {Denham, SS and Brignone, NF and Johnson, LA and Pozner, RE}, title = {Using integrative taxonomy and multispecies coalescent models for phylogeny reconstruction and species delimitation within the "Nastanthus-Gamocarpha" clade (Calyceraceae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {211-226}, doi = {10.1016/j.ympev.2018.10.015}, pmid = {30336217}, issn = {1095-9513}, abstract = {The Calyceraceae (47 spp.) is a small family of plants that is sister to the Asteraceae (∼ 25,000 spp.), one of the largest families of angiosperms. Most members of Calyceraceae are endemic to the Andes and Patagonia, representing an excellent model within which to study diversification patterns in these regions. The single phylogenetic study of Calyceraceae conducted to date revealed that the boundaries of most genera and several species of this family require further analyses, especially the "Nastanthus-Gamocarpha" clade. In this study, we reconstructed the phylogeny of the "Nastanthus-Gamocarpha" clade using multispecies coalescent models under BPP and StarBeast2 programs, sampling 63 individuals from 13 of the 14 species recognized to date. We then used this phylogenetic framework to delimit species using BFD and the A11 method implemented in BPP. Species limits suggested through a coalescent approach were then re-evaluated in the light of morphology, geography, and phenology. Coalescent-based methods indicated that most putative lineages could be recognized as distinct species. Morphological, geographical, ecological, and phenological data further supported species delimitation. Necessary taxonomic changes are proposed. Namely, the paraphyletic Nastanthus is synonymized under Gamocarpha, while five species of Boopis are transferred into Gamocarpha. We used an integrative taxonomic approach to recognize 13 species and one subspecies within the newly circumscribed genus Gamocarpha.}, } @article {pmid30336114, year = {2018}, author = {Suggs, BZ and Latham, AL and Dawes, AT and Chamberlin, HM}, title = {FACT complex gene duplicates exhibit redundant and non-redundant functions in C. elegans.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {71-82}, doi = {10.1016/j.ydbio.2018.10.002}, pmid = {30336114}, issn = {1095-564X}, support = {T32 GM086252/GM/NIGMS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; }, abstract = {FACT (facilitates chromatin transcription) is a histone chaperone complex important in genomic processes including transcription, DNA replication, and DNA repair. FACT is composed of two proteins, SSRP1 and SPT16, which are highly conserved across eukaryotes. While the mechanisms for FACT in nucleosome reorganization and its relationship to DNA processes is well established, how these roles impact coordination in multicellular animal development are less well understood. Here we characterize the genes encoding FACT complex proteins in the nematode C. elegans. We show that whereas C. elegans includes one SPT16 gene (spt-16), two genes (hmg-3 and hmg-4) encode SSRP1 proteins. Depletion of FACT complex genes interferes with embryonic cell division and cell cycle timing generally, with anterior pharynx development especially sensitive to these defects. hmg-3 and hmg-4 exhibit redundancy for these maternally-provided embryonic functions, but are each uniquely required zygotically for normal germline development. This work provides a framework to study FACT gene function in developmental processes, and identifies that distinct functional requirements for gene duplicates can be manifest within a single tissue.}, } @article {pmid30335146, year = {2018}, author = {Gnecchi-Ruscone, GA and Abondio, P and De Fanti, S and Sarno, S and Sherpa, MG and Sherpa, PT and Marinelli, G and Natali, L and Di Marcello, M and Peluzzi, D and Luiselli, D and Pettener, D and Sazzini, M}, title = {Evidence of Polygenic Adaptation to High Altitude from Tibetan and Sherpa Genomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2919-2930}, pmid = {30335146}, issn = {1759-6653}, support = {R01 HL119577/HL/NHLBI NIH HHS/United States ; }, abstract = {Although Tibetans and Sherpa present several physiological adjustments evolved to cope with selective pressures imposed by the high-altitude environment, especially hypobaric hypoxia, few selective sweeps at a limited number of hypoxia related genes were confirmed by multiple genomic studies. Nevertheless, variants at these loci were found to be associated only with downregulation of the erythropoietic cascade, which represents an indirect aspect of the considered adaptive phenotype. Accordingly, the genetic basis of Tibetan/Sherpa adaptive traits remains to be fully elucidated, in part due to limitations of selection scans implemented so far and mostly relying on the hard sweep model.In order to overcome this issue, we used whole-genome sequence data and several selection statistics as input for gene network analyses aimed at testing for the occurrence of polygenic adaptation in these high-altitude Himalayan populations. Being able to detect also subtle genomic signatures ascribable to weak positive selection at multiple genes of the same functional subnetwork, this approach allowed us to infer adaptive evolution at loci individually showing small effect sizes, but belonging to highly interconnected biological pathways overall involved in angiogenetic processes.Therefore, these findings pinpointed a series of selective events neglected so far, which likely contributed to the augmented tissue blood perfusion observed in Tibetans and Sherpa, thus uncovering the genetic determinants of a key biological mechanism that underlies their adaptation to high altitude.}, } @article {pmid30335145, year = {2018}, author = {Robertson, HM and Waterhouse, RM and Walden, KKO and Ruzzante, L and Reijnders, MJMF and Coates, BS and Legeai, F and Gress, JC and Biyiklioglu, S and Weaver, DK and Wanner, KW and Budak, H}, title = {Genome Sequence of the Wheat Stem Sawfly, Cephus cinctus, Representing an Early-Branching Lineage of the Hymenoptera, Illuminates Evolution of Hymenopteran Chemoreceptors.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2997-3011}, pmid = {30335145}, issn = {1759-6653}, abstract = {The wheat stem sawfly, Cephus cinctus, is a major pest of wheat and key ecological player in the grasslands of western North America. It also represents the distinctive Cephoidea superfamily of sawflies (Symphyta) that appeared early during the hymenopteran radiation, but after three early-branching eusymphytan superfamilies that form the base of the order Hymenoptera. We present a high-quality draft genome assembly of 162 Mb in 1,976 scaffolds with a scaffold N50 of 622 kb. Automated gene annotation identified 11,210 protein-coding gene models and 1,307 noncoding RNA models. Thirteen percent of the assembly consists of ∼58,000 transposable elements partitioned equally between Class-I and Class-II elements. Orthology analysis reveals that 86% of Cephus proteins have identifiable orthologs in other insects. Phylogenomic analysis of conserved subsets of these proteins supports the placement of the Cephoidea between the Eusymphyta and the parasitic woodwasp superfamily Orussoidea. Manual annotation and phylogenetic analysis of families of odorant, gustatory, and ionotropic receptors, plus odorant-binding proteins, shows that Cephus has representatives for most conserved and expanded gene lineages in the Apocrita (wasps, ants, and bees). Cephus has also maintained several insect gene lineages that have been lost from the Apocrita, most prominently the carbon dioxide receptor subfamily. Furthermore, Cephus encodes a few small lineage-specific chemoreceptor gene family expansions that might be involved in adaptations to new grasses including wheat. These comparative analyses identify gene family members likely to have been present in the hymenopteran ancestor and provide a new perspective on the evolution of the chemosensory gene repertoire.}, } @article {pmid30335144, year = {2018}, author = {Blakeway, LV and Tan, A and Lappan, R and Ariff, A and Pickering, JL and Peacock, CS and Blyth, CC and Kahler, CM and Chang, BJ and Lehmann, D and Kirkham, LS and Murphy, TF and Jennings, MP and Bakaletz, LO and Atack, JM and Peak, IR and Seib, KL}, title = {Moraxella catarrhalis Restriction-Modification Systems Are Associated with Phylogenetic Lineage and Disease.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2932-2946}, pmid = {30335144}, issn = {1759-6653}, support = {R01 DC012200/DC/NIDCD NIH HHS/United States ; N01AI30040/AI/NIAID NIH HHS/United States ; }, abstract = {Moraxella catarrhalis is a human-adapted pathogen, and a major cause of otitis media (OM) and exacerbations of chronic obstructive pulmonary disease. The species is comprised of two main phylogenetic lineages, RB1 and RB2/3. Restriction-modification (R-M) systems are among the few lineage-associated genes identified in other bacterial genera and have multiple functions including defense against foreign invading DNA, maintenance of speciation, and epigenetic regulation of gene expression. Here, we define the repertoire of R-M systems in 51 publicly available M. catarrhalis genomes and report their distribution among M. catarrhalis phylogenetic lineages. An association with phylogenetic lineage (RB1 or RB2/3) was observed for six R-M systems, which may contribute to the evolution of the lineages by restricting DNA transformation. In addition, we observed a relationship between a mutually exclusive Type I R-M system and a Type III R-M system at a single locus conserved throughout a geographically and clinically diverse set of M. catarrhalis isolates. The Type III R-M system at this locus contains the phase-variable Type III DNA methyltransferase, modM, which controls a phasevarion (phase-variable regulon). We observed an association between modM presence and OM-associated middle ear isolates, indicating a potential role for ModM-mediated epigenetic regulation in OM pathobiology.}, } @article {pmid30335126, year = {2018}, author = {Koh, C and Allen, SL and Herbert, RI and McGraw, EA and Chenoweth, SF}, title = {The Transcriptional Response of Aedes aegypti with Variable Extrinsic Incubation Periods for Dengue Virus.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3141-3151}, pmid = {30335126}, issn = {1759-6653}, abstract = {Dengue fever is the most prevalent arboviral disease globally. Dengue virus is transmitted primarily by the Aedes aegypti mosquito. One measure of the mosquito's efficiency as a vector is the extrinsic incubation period (EIP), which is the time between the ingestion of viremic blood and the emergence of virions in the saliva. The longer it takes virus to infect the midgut and traverse to the saliva, the fewer opportunities the mosquito will have to transmit the pathogen over its lifetime. We have shown previously that EIP for dengue virus is highly heritable and that it is negatively correlated with vector lifespan. Here, we examined the transcriptional profiles for mosquitoes that varied in their EIP phenotype and identified pathways associated with either short or long EIP. We found that mosquitoes with short EIP have less active immune responses but higher levels of protein translation and calcium ion homeostasis and that mosquitoes with longer EIP may have slower metabolism. These findings indicate a complex interplay between calcium ion distribution, ribosome biogenesis, and metabolism and reveal potential pathways that could be modified to slow the rate of viral progression and hence limit lifetime transmission capability.}, } @article {pmid30334341, year = {2018}, author = {Kiat, Y and Izhaki, I and Sapir, N}, title = {The effects of long-distance migration on the evolution of moult strategies in Western-Palearctic passerines.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12474}, pmid = {30334341}, issn = {1469-185X}, abstract = {Although feathers are the unifying characteristic of all birds, our understanding of the causes, mechanisms, patterns and consequences of the feather moult process lags behind that of other major avian life-history phenomena such as reproduction and long-distance migration. Migration, which evolved in many species of the temperate and arctic zones, requires high energy expenditure to endure long-distance journeys. About a third of Western-Palearctic passerines perform long-distance migrations of thousands of kilometres each year using various morphological, physiological, biomechanical, behavioural and life-history adaptations. The need to include the largely non-overlapping breeding, long-distance migration and feather moult processes within the annual cycle imposes a substantial constraint on the time over which the moult process can take place. Here, we review four feather-moult-related adaptations which, likely due to time constraints, evolved among long-distance Western-Palearctic migrants: (i) increased moult speed; (ii) increased overlap between moult and breeding or migration; (iii) decreased extent of plumage moult; and (iv) moult of part or all of the plumage during the over-wintering period in the tropics rather than in the breeding areas. We suggest that long-distance migration shaped the evolution of moult strategies and increased the diversity of these strategies among migratory passerines. In contrast to this variation, all resident passerines in the Western Palearctic moult immediately after breeding by renewing the entire plumage of adults and in some species also juveniles, while in other species juvenile moult is partial. We identify important gaps in our current understanding of the moult process that should be addressed in the future. Notably, previous studies suggested that the ancestral moult strategy is a post-breeding summer moult in the Western Palearctic breeding areas and that moult during the winter evolved due to the scheduling of long-distance migration immediately after breeding. We offer an alternative hypothesis based on the notion of southern ancestry, proposing that the ancestral moult strategy was a complete moult during the 'northern winter' in the Afro-tropical region in these species, for both adults and juveniles. An important aspect of the observed variation in moult strategies relates to their control mechanisms and we suggest that there is insufficient knowledge regarding the physiological mechanisms that are involved, and whether they are genetically fixed or shaped by environmental factors. Finally, research effort is needed on how global climate changes may influence avian annual routines by altering the scheduling of major processes such as long-distance migration and feather moult.}, } @article {pmid30334259, year = {2018}, author = {Smith, ML}, title = {Queenless honey bees build infrastructure for direct reproduction until their new queen proves her worth.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2810-2817}, doi = {10.1111/evo.13628}, pmid = {30334259}, issn = {1558-5646}, support = {1600775//National Science Foundation/ ; DGE-1144153//National Science Foundation/ ; }, abstract = {The terminal investment hypothesis predicts that individuals will alter their reproductive investments based on reproductive prospects. This hypothesis, however, has never been tested at the colony-level, where reproductive prospects for thousands of individuals can change instantly with the death of a single individual: the queen. A honey bee queen's death also changes the reproductive mechanism; if the queen is not replaced, then workers reproduce directly, by producing males in reproductive comb-drone comb-before the colony dies. To test how workers respond to reproductive uncertainty, I made colonies queenless and measured comb building throughout the stages of rearing a replacement queen. Queenless workers built only drone comb throughout queen rearing, even when the colony possessed a virgin or mated queen. Only when the new queen started laying fertilized eggs did workers stop building drone comb. Despite queenless colonies being more likely to eventually rear a replacement queen (88%), than to fail (12%), workers still built drone comb for direct reproduction, even when the colony was provided with ample drone comb. Therefore, workers "pessimistically" invest in drone comb to prepare for direct reproduction, even while rearing a replacement queen to prevent that outcome. When faced with reproductive uncertainty, honey bees may "hope" for the best, but they prepare for the worst.}, } @article {pmid30333630, year = {2018}, author = {Perraki, A and DeFalco, TA and Derbyshire, P and Avila, J and Séré, D and Sklenar, J and Qi, X and Stransfeld, L and Schwessinger, B and Kadota, Y and Macho, AP and Jiang, S and Couto, D and Torii, KU and Menke, FLH and Zipfel, C}, title = {Author Correction: Phosphocode-dependent functional dichotomy of a common co-receptor in plant signalling.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {E30}, doi = {10.1038/s41586-018-0663-4}, pmid = {30333630}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; }, abstract = {In Extended Data Fig. 5d of this Letter, the blots for anti-pS612 and anti-BAK1 were inadvertently duplicated. This figure has been corrected online.}, } @article {pmid30333629, year = {2018}, author = {Tanaka, M and Sun, F and Li, Y and Mooney, R}, title = {A mesocortical dopamine circuit enables the cultural transmission of vocal behaviour.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {117-120}, pmid = {30333629}, issn = {1476-4687}, support = {R01 NS099288/NS/NINDS NIH HHS/United States ; U01 NS103558/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cues ; Dopamine/*metabolism ; Dopaminergic Neurons/*metabolism ; Female ; Finches/*physiology ; Learning/*physiology ; Male ; Neural Pathways/*physiology ; Optogenetics ; Periaqueductal Gray/*cytology/*physiology ; Presynaptic Terminals/metabolism ; Signal Transduction ; Singing/physiology ; Vocalization, Animal/*physiology ; }, abstract = {The cultural transmission of behaviour depends on the ability of the pupil to identify and emulate an appropriate tutor1-4. How the brain of the pupil detects a suitable tutor and encodes the behaviour of the tutor is largely unknown. Juvenile zebra finches readily copy the songs of the adult tutors that they interact with, but not the songs that they listen to passively through a speaker5,6, indicating that social cues generated by the tutor facilitate song imitation. Here we show that neurons in the midbrain periaqueductal grey of juvenile finches are selectively excited by a singing tutor and-by releasing dopamine in the cortical song nucleus HVC-help to encode the song representations of the tutor used for vocal copying. Blocking dopamine signalling in the HVC of the pupil during tutoring blocked copying, whereas pairing stimulation of periaqueductal grey terminals in the HVC with a song played through a speaker was sufficient to drive copying. Exposure to a singing tutor triggered the rapid emergence of responses to the tutor song in the HVC of the pupil and a rapid increase in the complexity of the song of the pupil, an early signature of song copying7,8. These findings reveal that a dopaminergic mesocortical circuit detects the presence of a tutor and helps to encode the performance of the tutor, facilitating the cultural transmission of vocal behaviour.}, } @article {pmid30333628, year = {2018}, author = {Chen, HY and Fishbach, M and Holz, DE}, title = {A two per cent Hubble constant measurement from standard sirens within five years.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {545-547}, doi = {10.1038/s41586-018-0606-0}, pmid = {30333628}, issn = {1476-4687}, support = {PHY-1151836//National Science Foundation/International ; PHY-178081//National Science Foundation/International ; PHY-1125897//National Science Foundation/International ; DGE-1746045//National Science Foundation/International ; }, abstract = {Gravitational-wave detections provide a novel way to determine the Hubble constant1-3, which is the current rate of expansion of the Universe. This 'standard siren' method, with the absolute distance calibration provided by the general theory of relativity, was used to measure the Hubble constant using the gravitational-wave detection of the binary neutron-star merger, GW170817, by the Laser Interferometer Gravitational-Wave Observatory (LIGO) and Virgo4, combined with optical identification of the host galaxy5,6 NGC 4993. This independent measurement is of particular interest given the discrepancy between the value of the Hubble constant determined using type Ia supernovae via the local distance ladder (73.24 ± 1.74 kilometres per second per megaparsec) and the value determined from cosmic microwave background observations (67.4 ± 0.5 kilometres per second per megaparsec): these values differ7,8 by about 3σ. Local distance ladder observations may achieve a precision of one per cent within five years, but at present there are no indications that further observations will substantially reduce the existing discrepancies9. Here we show that additional gravitational-wave detections by LIGO and Virgo can be expected to constrain the Hubble constant to a precision of approximately two per cent within five years and approximately one per cent within a decade. This is because observing gravitational waves from the merger of two neutron stars, together with the identification of a host galaxy, enables a direct measurement of the Hubble constant independent of the systematics associated with other available methods. In addition to clarifying the discrepancy between existing low-redshift (local ladder) and high-redshift (cosmic microwave background) measurements, a precision measurement of the Hubble constant is of crucial value in elucidating the nature of dark energy10,11.}, } @article {pmid30333627, year = {2018}, author = {Tyner, JW and Tognon, CE and Bottomly, D and Wilmot, B and Kurtz, SE and Savage, SL and Long, N and Schultz, AR and Traer, E and Abel, M and Agarwal, A and Blucher, A and Borate, U and Bryant, J and Burke, R and Carlos, A and Carpenter, R and Carroll, J and Chang, BH and Coblentz, C and d'Almeida, A and Cook, R and Danilov, A and Dao, KT and Degnin, M and Devine, D and Dibb, J and Edwards, DK and Eide, CA and English, I and Glover, J and Henson, R and Ho, H and Jemal, A and Johnson, K and Johnson, R and Junio, B and Kaempf, A and Leonard, J and Lin, C and Liu, SQ and Lo, P and Loriaux, MM and Luty, S and Macey, T and MacManiman, J and Martinez, J and Mori, M and Nelson, D and Nichols, C and Peters, J and Ramsdill, J and Rofelty, A and Schuff, R and Searles, R and Segerdell, E and Smith, RL and Spurgeon, SE and Sweeney, T and Thapa, A and Visser, C and Wagner, J and Watanabe-Smith, K and Werth, K and Wolf, J and White, L and Yates, A and Zhang, H and Cogle, CR and Collins, RH and Connolly, DC and Deininger, MW and Drusbosky, L and Hourigan, CS and Jordan, CT and Kropf, P and Lin, TL and Martinez, ME and Medeiros, BC and Pallapati, RR and Pollyea, DA and Swords, RT and Watts, JM and Weir, SJ and Wiest, DL and Winters, RM and McWeeney, SK and Druker, BJ}, title = {Functional genomic landscape of acute myeloid leukaemia.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {526-531}, pmid = {30333627}, issn = {1476-4687}, support = {UL1 TR002369/TR/NCATS NIH HHS/United States ; U54 CA224019/CA/NCI NIH HHS/United States ; R01 CA214428/CA/NCI NIH HHS/United States ; KL2 TR000152/TR/NCATS NIH HHS/United States ; R01 CA183974/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 AI110985/AI/NIAID NIH HHS/United States ; T15 LM007088/LM/NLM NIH HHS/United States ; U01 CA217862/CA/NCI NIH HHS/United States ; P30 CA069533/CA/NCI NIH HHS/United States ; }, abstract = {The implementation of targeted therapies for acute myeloid leukaemia (AML) has been challenging because of the complex mutational patterns within and across patients as well as a dearth of pharmacologic agents for most mutational events. Here we report initial findings from the Beat AML programme on a cohort of 672 tumour specimens collected from 562 patients. We assessed these specimens using whole-exome sequencing, RNA sequencing and analyses of ex vivo drug sensitivity. Our data reveal mutational events that have not previously been detected in AML. We show that the response to drugs is associated with mutational status, including instances of drug sensitivity that are specific to combinatorial mutational events. Integration with RNA sequencing also revealed gene expression signatures, which predict a role for specific gene networks in the drug response. Collectively, we have generated a dataset-accessible through the Beat AML data viewer (Vizome)-that can be leveraged to address clinical, genomic, transcriptomic and functional analyses of the biology of AML.}, } @article {pmid30333626, year = {2018}, author = {Gao, Z and Davis, C and Thomas, AM and Economo, MN and Abrego, AM and Svoboda, K and De Zeeuw, CI and Li, N}, title = {A cortico-cerebellar loop for motor planning.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {113-116}, pmid = {30333626}, issn = {1476-4687}, support = {R21 NS104781/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cerebellum/cytology/*physiology ; Cues ; Female ; Frontal Lobe/cytology/*physiology ; Male ; Mice ; Movement/physiology ; Neural Pathways ; Neurons/physiology ; Psychomotor Performance/*physiology ; Thalamus/cytology/physiology ; }, abstract = {Persistent and ramping neural activity in the frontal cortex anticipates specific movements1-6. Preparatory activity is distributed across several brain regions7,8, but it is unclear which brain areas are involved and how this activity is mediated by multi-regional interactions. The cerebellum is thought to be primarily involved in the short-timescale control of movement9-12; however, roles for this structure in cognitive processes have also been proposed13-16. In humans, cerebellar damage can cause defects in planning and working memory13. Here we show that persistent representation of information in the frontal cortex during motor planning is dependent on the cerebellum. Mice performed a sensory discrimination task in which they used short-term memory to plan a future directional movement. A transient perturbation in the medial deep cerebellar nucleus (fastigial nucleus) disrupted subsequent correct responses without hampering movement execution. Preparatory activity was observed in both the frontal cortex and the cerebellar nuclei, seconds before the onset of movement. The silencing of frontal cortex activity abolished preparatory activity in the cerebellar nuclei, and fastigial activity was necessary to maintain cortical preparatory activity. Fastigial output selectively targeted the behaviourally relevant part of the frontal cortex through the thalamus, thus closing a cortico-cerebellar loop. Our results support the view that persistent neural dynamics during motor planning is maintained by neural circuits that span multiple brain regions17, and that cerebellar computations extend beyond online motor control13-15,18.}, } @article {pmid30333625, year = {2018}, author = {Deng, M and Gui, X and Kim, J and Xie, L and Chen, W and Li, Z and He, L and Chen, Y and Chen, H and Luo, W and Lu, Z and Xie, J and Churchill, H and Xu, Y and Zhou, Z and Wu, G and Yu, C and John, S and Hirayasu, K and Nguyen, N and Liu, X and Huang, F and Li, L and Deng, H and Tang, H and Sadek, AH and Zhang, L and Huang, T and Zou, Y and Chen, B and Zhu, H and Arase, H and Xia, N and Jiang, Y and Collins, R and You, MJ and Homsi, J and Unni, N and Lewis, C and Chen, GQ and Fu, YX and Liao, XC and An, Z and Zheng, J and Zhang, N and Zhang, CC}, title = {LILRB4 signalling in leukaemia cells mediates T cell suppression and tumour infiltration.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {605-609}, doi = {10.1038/s41586-018-0615-z}, pmid = {30333625}, issn = {1476-4687}, support = {P30 CA142543/CA/NCI NIH HHS/United States ; R01 CA172268/CA/NCI NIH HHS/United States ; }, abstract = {Immune checkpoint blockade therapy has been successful in treating some types of cancer but has not shown clinical benefits for treating leukaemia1. This result suggests that leukaemia uses unique mechanisms to evade this therapy. Certain immune inhibitory receptors that are expressed by normal immune cells are also present on leukaemia cells. Whether these receptors can initiate immune-related primary signalling in tumour cells remains unknown. Here we use mouse models and human cells to show that LILRB4, an immunoreceptor tyrosine-based inhibition motif-containing receptor and a marker of monocytic leukaemia, supports tumour cell infiltration into tissues and suppresses T cell activity via a signalling pathway that involves APOE, LILRB4, SHP-2, uPAR and ARG1 in acute myeloid leukaemia (AML) cells. Deletion of LILRB4 or the use of antibodies to block LILRB4 signalling impeded AML development. Thus, LILRB4 orchestrates tumour invasion pathways in monocytic leukaemia cells by creating an immunosuppressive microenvironment. LILRB4 represents a compelling target for the treatment of monocytic AML.}, } @article {pmid30333624, year = {2018}, author = {Müller, LSM and Cosentino, RO and Förstner, KU and Guizetti, J and Wedel, C and Kaplan, N and Janzen, CJ and Arampatzi, P and Vogel, J and Steinbiss, S and Otto, TD and Saliba, AE and Sebra, RP and Siegel, TN}, title = {Genome organization and DNA accessibility control antigenic variation in trypanosomes.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {121-125}, doi = {10.1038/s41586-018-0619-8}, pmid = {30333624}, issn = {1476-4687}, support = {098051//Wellcome Trust/United Kingdom ; }, mesh = {Antigenic Variation/*genetics ; Chromatin/*genetics/*metabolism ; DNA, Protozoan/genetics/*metabolism ; Genome/*genetics ; Haplotypes/genetics ; Histones/deficiency/genetics ; Multigene Family/genetics ; Protein Isoforms/biosynthesis/genetics ; Trypanosoma brucei brucei/*genetics/*immunology ; Variant Surface Glycoproteins, Trypanosoma/biosynthesis/genetics ; }, abstract = {Many evolutionarily distant pathogenic organisms have evolved similar survival strategies to evade the immune responses of their hosts. These include antigenic variation, through which an infecting organism prevents clearance by periodically altering the identity of proteins that are visible to the immune system of the host1. Antigenic variation requires large reservoirs of immunologically diverse antigen genes, which are often generated through homologous recombination, as well as mechanisms to ensure the expression of one or very few antigens at any given time. Both homologous recombination and gene expression are affected by three-dimensional genome architecture and local DNA accessibility2,3. Factors that link three-dimensional genome architecture, local chromatin conformation and antigenic variation have, to our knowledge, not yet been identified in any organism. One of the major obstacles to studying the role of genome architecture in antigenic variation has been the highly repetitive nature and heterozygosity of antigen-gene arrays, which has precluded complete genome assembly in many pathogens. Here we report the de novo haplotype-specific assembly and scaffolding of the long antigen-gene arrays of the model protozoan parasite Trypanosoma brucei, using long-read sequencing technology and conserved features of chromosome folding4. Genome-wide chromosome conformation capture (Hi-C) reveals a distinct partitioning of the genome, with antigen-encoding subtelomeric regions that are folded into distinct, highly compact compartments. In addition, we performed a range of analyses-Hi-C, fluorescence in situ hybridization, assays for transposase-accessible chromatin using sequencing and single-cell RNA sequencing-that showed that deletion of the histone variants H3.V and H4.V increases antigen-gene clustering, DNA accessibility across sites of antigen expression and switching of the expressed antigen isoform, via homologous recombination. Our analyses identify histone variants as a molecular link between global genome architecture, local chromatin conformation and antigenic variation.}, } @article {pmid30333623, year = {2018}, author = {Pennekamp, F and Pontarp, M and Tabi, A and Altermatt, F and Alther, R and Choffat, Y and Fronhofer, EA and Ganesanandamoorthy, P and Garnier, A and Griffiths, JI and Greene, S and Horgan, K and Massie, TM and Mächler, E and Palamara, GM and Seymour, M and Petchey, OL}, title = {Biodiversity increases and decreases ecosystem stability.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {109-112}, doi = {10.1038/s41586-018-0627-8}, pmid = {30333623}, issn = {1476-4687}, mesh = {*Aquatic Organisms ; *Biodiversity ; Biomass ; Ciliophora/*classification/*physiology ; Food Chain ; Microbiology ; Models, Biological ; }, abstract = {Losses and gains in species diversity affect ecological stability1-7 and the sustainability of ecosystem functions and services8-13. Experiments and models have revealed positive, negative and no effects of diversity on individual components of stability, such as temporal variability, resistance and resilience2,3,6,11,12,14. How these stability components covary remains poorly understood15. Similarly, the effects of diversity on overall ecosystem stability16, which is conceptually akin to ecosystem multifunctionality17,18, remain unknown. Here we studied communities of aquatic ciliates to understand how temporal variability, resistance and overall ecosystem stability responded to diversity (that is, species richness) in a large experiment involving 690 micro-ecosystems sampled 19 times over 40 days, resulting in 12,939 samplings. Species richness increased temporal stability but decreased resistance to warming. Thus, two stability components covaried negatively along the diversity gradient. Previous biodiversity manipulation studies rarely reported such negative covariation despite general predictions of the negative effects of diversity on individual stability components3. Integrating our findings with the ecosystem multifunctionality concept revealed hump- and U-shaped effects of diversity on overall ecosystem stability. That is, biodiversity can increase overall ecosystem stability when biodiversity is low, and decrease it when biodiversity is high, or the opposite with a U-shaped relationship. The effects of diversity on ecosystem multifunctionality would also be hump- or U-shaped if diversity had positive effects on some functions and negative effects on others. Linking the ecosystem multifunctionality concept and ecosystem stability can transform the perceived effects of diversity on ecological stability and may help to translate this science into policy-relevant information.}, } @article {pmid30333622, year = {2018}, author = {Sugita, Y and Matsunami, H and Kawaoka, Y and Noda, T and Wolf, M}, title = {Cryo-EM structure of the Ebola virus nucleoprotein-RNA complex at 3.6 Å resolution.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {137-140}, doi = {10.1038/s41586-018-0630-0}, pmid = {30333622}, issn = {1476-4687}, mesh = {*Cryoelectron Microscopy ; Ebolavirus/*chemistry/*ultrastructure ; HEK293 Cells ; Humans ; Models, Molecular ; Nucleocapsid/*chemistry/ultrastructure ; RNA, Viral/*chemistry/ultrastructure ; }, abstract = {Ebola virus causes haemorrhagic fever with a high fatality rate in humans and non-human primates. It belongs to the family Filoviridae in the order Mononegavirales, which are viruses that contain linear, non-segmented, negative-sense, single-stranded genomic RNA1,2. The enveloped, filamentous virion contains the nucleocapsid, consisting of the helical nucleoprotein-RNA complex, VP24, VP30, VP35 and viral polymerase1,3. The nucleoprotein-RNA complex acts as a scaffold for nucleocapsid formation and as a template for RNA replication and transcription by condensing RNA into the virion4,5. RNA binding and nucleoprotein oligomerization are synergistic and do not readily occur independently6. Although recent cryo-electron tomography studies have revealed the overall architecture of the nucleocapsid core4,5, there has been no high-resolution reconstruction of the nucleocapsid. Here we report the structure of a recombinant Ebola virus nucleoprotein-RNA complex expressed in mammalian cells without chemical fixation, at near-atomic resolution using single-particle cryo-electron microscopy. Our structure reveals how the Ebola virus nucleocapsid core encapsidates its viral genome, its sequence-independent coordination with RNA by nucleoprotein, and the dynamic transition between the RNA-free and RNA-bound states. It provides direct structural evidence for the role of the N terminus of nucleoprotein in subunit oligomerization, and for the hydrophobic and electrostatic interactions that lead to the formation of the helical assembly. The structure is validated as representative of the native biological assembly of the nucleocapsid core by consistent dimensions and symmetry with the full virion5. The atomic model provides a detailed mechanistic basis for understanding nucleocapsid assembly and highlights key structural features that may serve as targets for anti-viral drug development.}, } @article {pmid30333621, year = {2018}, author = {Allwood, AC and Rosing, MT and Flannery, DT and Hurowitz, JA and Heirwegh, CM}, title = {Reassessing evidence of life in 3,700-million-year-old rocks of Greenland.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {241-244}, doi = {10.1038/s41586-018-0610-4}, pmid = {30333621}, issn = {1476-4687}, abstract = {The Palaeoarchean supracrustal belts in Greenland contain Earth's oldest rocks and are a prime target in the search for the earliest evidence of life on Earth. However, metamorphism has largely obliterated original rock textures and compositions, posing a challenge to the preservation of biological signatures. A recent study of 3,700-million-year-old rocks of the Isua supracrustal belt in Greenland described a rare zone in which low deformation and a closed metamorphic system allowed preservation of primary sedimentary features, including putative conical and domical stromatolites1 (laminated accretionary structures formed by microbially mediated sedimentation). The morphology, layering, mineralogy, chemistry and geological context of the structures were attributed to the formation of microbial mats in a shallow marine environment by 3,700 million years ago, at the start of Earth's rock record. Here we report new research that shows a non-biological, post-depositional origin for the structures. Three-dimensional analysis of the morphology and orientation of the structures within the context of host rock fabrics, combined with texture-specific analyses of major and trace element chemistry, show that the 'stromatolites' are more plausibly interpreted as part of an assemblage of deformation structures formed in carbonate-altered metasediments long after burial. The investigation of the structures of the Isua supracrustal belt serves as a cautionary tale in the search for signs of past life on Mars, highlighting the importance of three-dimensional, integrated analysis of morphology, rock fabrics and geochemistry at appropriate scales.}, } @article {pmid30333605, year = {2018}, author = {Leeming, J}, title = {Western Australia's science finds strength in its isolation.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {S105-S107}, doi = {10.1038/d41586-018-07045-1}, pmid = {30333605}, issn = {1476-4687}, } @article {pmid30333603, year = {2018}, author = {Laursen, L}, title = {How building trust has proved central to overcoming malaria.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {S62-S63}, doi = {10.1038/d41586-018-06972-3}, pmid = {30333603}, issn = {1476-4687}, } @article {pmid30333602, year = {2018}, author = {Hodson, R}, title = {Science without borders.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {S57}, doi = {10.1038/d41586-018-06970-5}, pmid = {30333602}, issn = {1476-4687}, } @article {pmid30333601, year = {2018}, author = {Nordling, L}, title = {Paths to success for African scientists.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {S58-S61}, doi = {10.1038/d41586-018-06971-4}, pmid = {30333601}, issn = {1476-4687}, } @article {pmid30333600, year = {2018}, author = {Hodson, R}, title = {Science without borders: 4 big questions.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {S68}, doi = {10.1038/d41586-018-06975-0}, pmid = {30333600}, issn = {1476-4687}, } @article {pmid30333599, year = {2018}, author = {Schmidt, C}, title = {The fight against non-communicable disease in emerging economies.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {S65-S67}, doi = {10.1038/d41586-018-06974-1}, pmid = {30333599}, issn = {1476-4687}, } @article {pmid30333598, year = {2018}, author = {Laursen, L}, title = {A call for early-career scientists to build a global science accord.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {S64}, doi = {10.1038/d41586-018-06973-2}, pmid = {30333598}, issn = {1476-4687}, } @article {pmid30333597, year = {2018}, author = {Dolgin, E}, title = {What legal weed in Canada means for science.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {327-330}, doi = {10.1038/d41586-018-07037-1}, pmid = {30333597}, issn = {1476-4687}, } @article {pmid30333596, year = {2018}, author = {}, title = {Rocket crash, alcohol warnings and astronomy's leaky pipeline.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {312-313}, doi = {10.1038/d41586-018-07035-3}, pmid = {30333596}, issn = {1476-4687}, } @article {pmid30333595, year = {2018}, author = {}, title = {Progress on antibiotic resistance.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {307}, doi = {10.1038/d41586-018-07031-7}, pmid = {30333595}, issn = {1476-4687}, } @article {pmid30333594, year = {2018}, author = {}, title = {Revealed: the extraordinary flight of the dandelion.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {307-308}, doi = {10.1038/d41586-018-07032-6}, pmid = {30333594}, issn = {1476-4687}, } @article {pmid30333592, year = {2018}, author = {Spires, DAX}, title = {Ferromagnetism.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {454}, doi = {10.1038/d41586-018-07050-4}, pmid = {30333592}, issn = {1476-4687}, } @article {pmid30333591, year = {2018}, author = {Liu, L}, title = {Exploring the Universe with matter waves.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {351-352}, doi = {10.1038/d41586-018-07009-5}, pmid = {30333591}, issn = {1476-4687}, mesh = {Electromagnetic Phenomena ; Interferometry ; *Physics ; *Time ; }, } @article {pmid30333590, year = {2018}, author = {Jouary, A and Machens, CK}, title = {A living display system resolved pixel by pixel.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {350-351}, doi = {10.1038/d41586-018-05909-0}, pmid = {30333590}, issn = {1476-4687}, } @article {pmid30333589, year = {2018}, author = {Turchi, C}, title = {Cermet material could aid the development of future power plants.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {346-347}, doi = {10.1038/d41586-018-07005-9}, pmid = {30333589}, issn = {1476-4687}, mesh = {Ceramics ; *Cermet Cements ; *Hot Temperature ; Metals ; Power Plants ; }, } @article {pmid30333588, year = {2018}, author = {}, title = {Why China is a hotspot for international students.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {451}, doi = {10.1038/d41586-018-07048-y}, pmid = {30333588}, issn = {1476-4687}, } @article {pmid30333587, year = {2018}, author = {}, title = {Why fewer women than men ask questions at conferences.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {451}, doi = {10.1038/d41586-018-07049-x}, pmid = {30333587}, issn = {1476-4687}, } @article {pmid30333586, year = {2018}, author = {Stroud, JL}, title = {Co-produced data: open access tests trust.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {344}, doi = {10.1038/d41586-018-07059-9}, pmid = {30333586}, issn = {1476-4687}, } @article {pmid30333585, year = {2018}, author = {Moss, SE}, title = {No need for juvenile language in Nature.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {344}, doi = {10.1038/d41586-018-07061-1}, pmid = {30333585}, issn = {1476-4687}, } @article {pmid30333584, year = {2018}, author = {Bethke, N and Gellert, P and Seybold, J}, title = {Encourage early-career scientists to shape policy.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {344}, doi = {10.1038/d41586-018-07057-x}, pmid = {30333584}, issn = {1476-4687}, } @article {pmid30333583, year = {2018}, author = {, }, title = {Improved limit on the electric dipole moment of the electron.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {355-360}, doi = {10.1038/s41586-018-0599-8}, pmid = {30333583}, issn = {1476-4687}, abstract = {The standard model of particle physics accurately describes all particle physics measurements made so far in the laboratory. However, it is unable to answer many questions that arise from cosmological observations, such as the nature of dark matter and why matter dominates over antimatter throughout the Universe. Theories that contain particles and interactions beyond the standard model, such as models that incorporate supersymmetry, may explain these phenomena. Such particles appear in the vacuum and interact with common particles to modify their properties. For example, the existence of very massive particles whose interactions violate time-reversal symmetry, which could explain the cosmological matter-antimatter asymmetry, can give rise to an electric dipole moment along the spin axis of the electron. No electric dipole moments of fundamental particles have been observed. However, dipole moments only slightly smaller than the current experimental bounds have been predicted to arise from particles more massive than any known to exist. Here we present an improved experimental limit on the electric dipole moment of the electron, obtained by measuring the electron spin precession in a superposition of quantum states of electrons subjected to a huge intramolecular electric field. The sensitivity of our measurement is more than one order of magnitude better than any previous measurement. This result implies that a broad class of conjectured particles, if they exist and time-reversal symmetry is maximally violated, have masses that greatly exceed what can be measured directly at the Large Hadron Collider.}, } @article {pmid30333582, year = {2018}, author = {Oestringer, BP and Bolivar, JH and Hensen, M and Claridge, JK and Chipot, C and Dehez, F and Holzmann, N and Zitzmann, N and Schnell, JR}, title = {Re-evaluating the p7 viroporin structure.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {E8-E18}, doi = {10.1038/s41586-018-0561-9}, pmid = {30333582}, issn = {1476-4687}, support = {MR/K018590/1//Medical Research Council/United Kingdom ; }, } @article {pmid30333581, year = {2018}, author = {Chen, W and OuYang, B and Chou, JJ}, title = {Chen et al. reply.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {E19-E20}, doi = {10.1038/s41586-018-0562-8}, pmid = {30333581}, issn = {1476-4687}, } @article {pmid30333580, year = {2018}, author = {Caccia, M and Tabandeh-Khorshid, M and Itskos, G and Strayer, AR and Caldwell, AS and Pidaparti, S and Singnisai, S and Rohskopf, AD and Schroeder, AM and Jarrahbashi, D and Kang, T and Sahoo, S and Kadasala, NR and Marquez-Rossy, A and Anderson, MH and Lara-Curzio, E and Ranjan, D and Henry, A and Sandhage, KH}, title = {Ceramic-metal composites for heat exchangers in concentrated solar power plants.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {406-409}, doi = {10.1038/s41586-018-0593-1}, pmid = {30333580}, issn = {1476-4687}, support = {DE-EE0007117//US Department of Energy/International ; }, abstract = {The efficiency of generating electricity from heat using concentrated solar power plants (which use mirrors or lenses to concentrate sunlight in order to drive heat engines, usually involving turbines) may be appreciably increased by operating with higher turbine inlet temperatures, but this would require improved heat exchanger materials. By operating turbines with inlet temperatures above 1,023 kelvin using closed-cycle high-pressure supercritical carbon dioxide (sCO2) recompression cycles, instead of using conventional (such as subcritical steam Rankine) cycles with inlet temperatures below 823 kelvin1-3, the relative heat-to-electricity conversion efficiency may be increased by more than 20 per cent. The resulting reduction in the cost of dispatchable electricity from concentrated solar power plants (coupled with thermal energy storage4-6) would be an important step towards direct competition with fossil-fuel-based plants and a large reduction in greenhouse gas emissions7. However, the inlet temperatures of closed-cycle high-pressure sCO2 turbine systems are limited8 by the thermomechanical performance of the compact, metal-alloy-based, printed-circuit-type heat exchangers used to transfer heat to sCO2. Here we present a robust composite of ceramic (zirconium carbide, ZrC) and the refractory metal tungsten (W) for use in printed-circuit-type heat exchangers at temperatures above 1,023 kelvin9. This composite has attractive high-temperature thermal, mechanical and chemical properties and can be processed in a cost-effective manner. We fabricated ZrC/W-based heat exchanger plates with tunable channel patterns by the shape-and-size-preserving chemical conversion of porous tungsten carbide plates. The dense ZrC/W-based composites exhibited failure strengths of over 350 megapascals at 1,073 kelvin, and thermal conductivity values two to three times greater than those of iron- or nickel-based alloys at this temperature. Corrosion resistance to sCO2 at 1,023 kelvin and 20 megapascals was achieved10 by bonding a copper layer to the composite surface and adding 50 parts per million carbon monoxide to sCO2. Techno-economic analyses indicate that ZrC/W-based heat exchangers can strongly outperform nickel-superalloy-based printed-circuit heat exchangers at lower cost.}, } @article {pmid30333579, year = {2018}, author = {Cummins, C and Seale, M and Macente, A and Certini, D and Mastropaolo, E and Viola, IM and Nakayama, N}, title = {A separated vortex ring underlies the flight of the dandelion.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {414-418}, doi = {10.1038/s41586-018-0604-2}, pmid = {30333579}, issn = {1476-4687}, abstract = {Wind-dispersed plants have evolved ingenious ways to lift their seeds1,2. The common dandelion uses a bundle of drag-enhancing bristles (the pappus) that helps to keep their seeds aloft. This passive flight mechanism is highly effective, enabling seed dispersal over formidable distances3,4; however, the physics underpinning pappus-mediated flight remains unresolved. Here we visualized the flow around dandelion seeds, uncovering an extraordinary type of vortex. This vortex is a ring of recirculating fluid, which is detached owing to the flow passing through the pappus. We hypothesized that the circular disk-like geometry and the porosity of the pappus are the key design features that enable the formation of the separated vortex ring. The porosity gradient was surveyed using microfabricated disks, and a disk with a similar porosity was found to be able to recapitulate the flow behaviour of the pappus. The porosity of the dandelion pappus appears to be tuned precisely to stabilize the vortex, while maximizing aerodynamic loading and minimizing material requirements. The discovery of the separated vortex ring provides evidence of the existence of a new class of fluid behaviour around fluid-immersed bodies that may underlie locomotion, weight reduction and particle retention in biological and manmade structures.}, } @article {pmid30333578, year = {2018}, author = {Reiter, S and Hülsdunk, P and Woo, T and Lauterbach, MA and Eberle, JS and Akay, LA and Longo, A and Meier-Credo, J and Kretschmer, F and Langer, JD and Kaschube, M and Laurent, G}, title = {Elucidating the control and development of skin patterning in cuttlefish.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {361-366}, pmid = {30333578}, issn = {1476-4687}, abstract = {Few animals provide a readout that is as objective of their perceptual state as camouflaging cephalopods. Their skin display system includes an extensive array of pigment cells (chromatophores), each expandable by radial muscles controlled by motor neurons. If one could track the individual expansion states of the chromatophores, one would obtain a quantitative description-and potentially even a neural description by proxy-of the perceptual state of the animal in real time. Here we present the use of computational and analytical methods to achieve this in behaving animals, quantifying the states of tens of thousands of chromatophores at sixty frames per second, at single-cell resolution, and over weeks. We infer a statistical hierarchy of motor control, reveal an underlying low-dimensional structure to pattern dynamics and uncover rules that govern the development of skin patterns. This approach provides an objective description of complex perceptual behaviour, and a powerful means to uncover the organizational principles that underlie the function, dynamics and morphogenesis of neural systems.}, } @article {pmid30333577, year = {2018}, author = {Hoogakker, BAA and Lu, Z and Umling, N and Jones, L and Zhou, X and Rickaby, REM and Thunell, R and Cartapanis, O and Galbraith, E}, title = {Glacial expansion of oxygen-depleted seawater in the eastern tropical Pacific.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {410-413}, doi = {10.1038/s41586-018-0589-x}, pmid = {30333577}, issn = {1476-4687}, abstract = {Increased storage of carbon in the oceans has been proposed as a mechanism to explain lower concentrations of atmospheric carbon dioxide during ice ages; however, unequivocal signatures of this storage have not been found1. In seawater, the dissolved gases oxygen and carbon dioxide are linked via the production and decay of organic material, with reconstructions of low oxygen concentrations in the past indicating an increase in biologically mediated carbon storage. Marine sediment proxy records have suggested that oxygen concentrations in the deep ocean were indeed lower during the last ice age, but that near-surface and intermediate waters of the Pacific Ocean-a large fraction of which are poorly oxygenated at present-were generally better oxygenated during the glacial1-3. This vertical opposition could suggest a minimal net basin-integrated change in carbon storage. Here we apply a dual-proxy approach, incorporating qualitative upper-water-column and quantitative bottom-water oxygen reconstructions4,5, to constrain changes in the vertical extent of low-oxygen waters in the eastern tropical Pacific since the last ice age. Our tandem proxy reconstructions provide evidence of a downward expansion of oxygen depletion in the eastern Pacific during the last glacial, with no indication of greater oxygenation in the upper reaches of the water column. We extrapolate our quantitative deep-water oxygen reconstructions to show that the respired carbon reservoir of the glacial Pacific was substantially increased, establishing it as an important component of the coupled mechanism that led to low levels of atmospheric carbon dioxide during the glacial.}, } @article {pmid30333576, year = {2018}, author = {Becker, D and Lachmann, MD and Seidel, ST and Ahlers, H and Dinkelaker, AN and Grosse, J and Hellmig, O and Müntinga, H and Schkolnik, V and Wendrich, T and Wenzlawski, A and Weps, B and Corgier, R and Franz, T and Gaaloul, N and Herr, W and Lüdtke, D and Popp, M and Amri, S and Duncker, H and Erbe, M and Kohfeldt, A and Kubelka-Lange, A and Braxmaier, C and Charron, E and Ertmer, W and Krutzik, M and Lämmerzahl, C and Peters, A and Schleich, WP and Sengstock, K and Walser, R and Wicht, A and Windpassinger, P and Rasel, EM}, title = {Space-borne Bose-Einstein condensation for precision interferometry.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {391-395}, doi = {10.1038/s41586-018-0605-1}, pmid = {30333576}, issn = {1476-4687}, abstract = {Owing to the low-gravity conditions in space, space-borne laboratories enable experiments with extended free-fall times. Because Bose-Einstein condensates have an extremely low expansion energy, space-borne atom interferometers based on Bose-Einstein condensation have the potential to have much greater sensitivity to inertial forces than do similar ground-based interferometers. On 23 January 2017, as part of the sounding-rocket mission MAIUS-1, we created Bose-Einstein condensates in space and conducted 110 experiments central to matter-wave interferometry, including laser cooling and trapping of atoms in the presence of the large accelerations experienced during launch. Here we report on experiments conducted during the six minutes of in-space flight in which we studied the phase transition from a thermal ensemble to a Bose-Einstein condensate and the collective dynamics of the resulting condensate. Our results provide insights into conducting cold-atom experiments in space, such as precision interferometry, and pave the way to miniaturizing cold-atom and photon-based quantum information concepts for satellite-based implementation. In addition, space-borne Bose-Einstein condensation opens up the possibility of quantum gas experiments in low-gravity conditions1,2.}, } @article {pmid30333189, year = {2018}, author = {Quinn, CM and Wang, M and Fritz, MP and Runge, B and Ahn, J and Xu, C and Perilla, JR and Gronenborn, AM and Polenova, T}, title = {Dynamic regulation of HIV-1 capsid interaction with the restriction factor TRIM5α identified by magic-angle spinning NMR and molecular dynamics simulations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11519-11524}, pmid = {30333189}, issn = {1091-6490}, support = {F32 GM113452/GM/NIGMS NIH HHS/United States ; P30 GM103519/GM/NIGMS NIH HHS/United States ; P30 GM110758/GM/NIGMS NIH HHS/United States ; P50 GM082251/GM/NIGMS NIH HHS/United States ; }, abstract = {The host factor protein TRIM5α plays an important role in restricting the host range of HIV-1, interfering with the integrity of the HIV-1 capsid. TRIM5 triggers an antiviral innate immune response by functioning as a capsid pattern recognition receptor, although the precise mechanism by which the restriction is imposed is not completely understood. Here we used an integrated magic-angle spinning nuclear magnetic resonance and molecular dynamics simulations approach to characterize, at atomic resolution, the dynamics of the capsid's hexameric and pentameric building blocks, and the interactions with TRIM5α in the assembled capsid. Our data indicate that assemblies in the presence of the pentameric subunits are more rigid on the microsecond to millisecond timescales than tubes containing only hexamers. This feature may be of key importance for controlling the capsid's morphology and stability. In addition, we found that TRIM5α binding to capsid induces global rigidification and perturbs key intermolecular interfaces essential for higher-order capsid assembly, with structural and dynamic changes occurring throughout the entire CA polypeptide chain in the assembly, rather than being limited to a specific protein-protein interface. Taken together, our results suggest that TRIM5α uses several mechanisms to destabilize the capsid lattice, ultimately inducing its disassembly. Our findings add to a growing body of work indicating that dynamic allostery plays a pivotal role in capsid assembly and HIV-1 infectivity.}, } @article {pmid30333188, year = {2018}, author = {Sement, FM and Suematsu, T and Zhang, L and Yu, T and Huang, L and Aphasizheva, I and Aphasizhev, R}, title = {Transcription initiation defines kinetoplast RNA boundaries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10323-E10332}, pmid = {30333188}, issn = {1091-6490}, support = {R01 AI091914/AI/NIAID NIH HHS/United States ; R01 AI113157/AI/NIAID NIH HHS/United States ; R01 AI101057/AI/NIAID NIH HHS/United States ; R01 GM106003/GM/NIGMS NIH HHS/United States ; R01 GM074830/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA, Kinetoplast ; Mitochondria/genetics ; Polyadenylation/genetics ; Protozoan Proteins/genetics ; RNA Editing/genetics ; RNA, Antisense/genetics ; RNA, Protozoan/*genetics ; Transcription, Genetic/*genetics ; Trypanosoma brucei brucei/*genetics ; }, abstract = {Mitochondrial genomes are often transcribed into polycistronic RNAs punctuated by tRNAs whose excision defines mature RNA boundaries. Although kinetoplast DNA lacks tRNA genes, it is commonly held that in Trypanosoma brucei the monophosphorylated 5' ends of functional molecules typify precursor partitioning by an unknown endonuclease. On the contrary, we demonstrate that individual mRNAs and rRNAs are independently synthesized as 3'-extended precursors. The transcription-defined 5' terminus is converted into a monophosphorylated state by the pyrophosphohydrolase complex, termed the "PPsome." Composed of the MERS1 NUDIX enzyme, the MERS2 pentatricopeptide repeat RNA-binding subunit, and MERS3 polypeptide, the PPsome binds to specific sequences near mRNA 5' termini. Most guide RNAs lack PPsome-recognition sites and remain triphosphorylated. The RNA-editing substrate-binding complex stimulates MERS1 pyrophosphohydrolase activity and enables an interaction between the PPsome and the polyadenylation machinery. We provide evidence that both 5' pyrophosphate removal and 3' adenylation are essential for mRNA stabilization. Furthermore, we uncover a mechanism by which antisense RNA-controlled 3'-5' exonucleolytic trimming defines the mRNA 3' end before adenylation. We conclude that mitochondrial mRNAs and rRNAs are transcribed and processed as insulated units irrespective of their genomic location.}, } @article {pmid30333187, year = {2018}, author = {Yao, Q and Cao, G and Li, M and Wu, B and Zhang, X and Zhang, T and Guo, J and Yin, H and Shi, L and Chen, J and Yu, X and Zheng, L and Ma, J and Su, YQ}, title = {Ribonuclease activity of MARF1 controls oocyte RNA homeostasis and genome integrity in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11250-11255}, pmid = {30333187}, issn = {1091-6490}, mesh = {Animals ; Aspartic Acid/genetics ; Catalytic Domain/genetics ; Cell Cycle Proteins/*metabolism ; DNA Breaks, Double-Stranded ; Female ; Genome/*genetics ; Homeostasis/*genetics ; Infertility, Female/genetics/metabolism ; Meiosis/genetics ; Mice ; Mutation/genetics ; Oocytes/*metabolism ; Phenotype ; RNA/*genetics ; Retroelements/genetics ; Ribonuclease H/*metabolism ; }, abstract = {Producing normal eggs for fertilization and species propagation requires completion of meiosis and protection of the genome from the ravages of retrotransposons. Mutation of Marf1 (meiosis regulator and mRNA stability factor 1) results in defects in both these key processes in mouse oocytes and thus in infertility. MARF1 was predicted to have ribonuclease activity, but the structural basis for the function of MARF1 and the contribution of its putative ribonuclease domain to the mutant oocyte phenotype was unknown. Therefore, we resolved the crystal structures of key domains of MARF1 and demonstrated by biochemical and mutagenic analyses that the ribonuclease activity of MARF1 controls oocyte meiotic progression and retrotransposon surveillance. The N-terminal NYN domain of MARF1 resembles the nuclease domains of Vpa0982, T4 RNase H, and MCPIP1 and contains four conserved aspartate residues, D178, D215, D246, and D272. The C-terminal LOTUS domain of MARF1 adopts a winged helix-turn-helix fold and binds ssRNA and dsRNA. Purified MARF1 cleaved ssRNAs in vitro, but this cleavage activity was abolished by mutations of conserved aspartates in its NYN domain and truncation of the LOTUS domain. Furthermore, a point mutation in the D272 residue in vivo caused a female-only infertile phenotype in mice, with failure of meiotic resumption and elevation of Line1 and Iap retrotransposon transcripts and DNA double-strand breaks in oocytes. Therefore, the ribonuclease activity of MARF1 controls oocyte meiosis and genome integrity. This activity depends upon conserved aspartic residues in the catalytic NYN domain and the RNA-binding activity of the LOTUS domain.}, } @article {pmid30333186, year = {2018}, author = {Sharkey, LM and Safren, N and Pithadia, AS and Gerson, JE and Dulchavsky, M and Fischer, S and Patel, R and Lantis, G and Ashraf, N and Kim, JH and Meliki, A and Minakawa, EN and Barmada, SJ and Ivanova, MI and Paulson, HL}, title = {Mutant UBQLN2 promotes toxicity by modulating intrinsic self-assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10495-E10504}, pmid = {30333186}, issn = {1091-6490}, support = {R01 NS096785/NS/NINDS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Vesicular Transport/genetics/*metabolism ; Amyotrophic Lateral Sclerosis/genetics/metabolism ; Animals ; Frontotemporal Dementia/genetics/metabolism ; Gene Expression Regulation ; Mice ; Mice, Transgenic ; Mutation ; Neurons ; *Protein Aggregation, Pathological ; Protein Conformation ; Protein Domains ; Ubiquitin ; }, abstract = {UBQLN2 is one of a family of proteins implicated in ubiquitin-dependent protein quality control and integrally tied to human neurodegenerative disease. Whereas wild-type UBQLN2 accumulates in intraneuronal deposits in several common age-related neurodegenerative diseases, mutations in the gene encoding this protein result in X-linked amyotrophic lateral sclerosis/frontotemporal dementia associated with TDP43 accumulation. Using in vitro protein analysis, longitudinal fluorescence imaging and cellular, neuronal, and transgenic mouse models, we establish that UBQLN2 is intrinsically prone to self-assemble into higher-order complexes, including liquid-like droplets and amyloid aggregates. UBQLN2 self-assembly and solubility are reciprocally modulated by the protein's ubiquitin-like and ubiquitin-associated domains. Moreover, a pathogenic UBQLN2 missense mutation impairs droplet dynamics and favors amyloid-like aggregation associated with neurotoxicity. These data emphasize the critical link between UBQLN2's role in ubiquitin-dependent pathways and its propensity to self-assemble and aggregate in neurodegenerative diseases.}, } @article {pmid30333185, year = {2018}, author = {Jeevanjee, N and Romps, DM}, title = {Mean precipitation change from a deepening troposphere.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11465-11470}, pmid = {30333185}, issn = {1091-6490}, abstract = {Global climate models robustly predict that global mean precipitation should increase at roughly 2-3% [Formula: see text], but the origin of these values is not well understood. Here we develop a simple theory to help explain these values. This theory combines the well-known radiative constraint on precipitation, which says that condensation heating from precipitation is balanced by the net radiative cooling of the free troposphere, with an invariance of radiative cooling profiles when expressed in temperature coordinates. These two constraints yield a picture in which mean precipitation is controlled primarily by the depth of the troposphere, when measured in temperature coordinates. We develop this theory in idealized simulations of radiative-convective equilibrium and also demonstrate its applicability to global climate models.}, } @article {pmid30333068, year = {2018}, author = {Volodin, IA and Sibiryakova, OV and Vasilieva, NA and Volodina, EV and Matrosova, VA and Garcia, AJ and Pérez-Barbería, FJ and Gallego, L and Landete-Castillejos, T}, title = {Between-year vocal aging in female red deer (Cervus elaphus).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {737}, pmid = {30333068}, issn = {1756-0500}, support = {14-14-00237//Russian Science Foundation/ ; RTC-2016-5327-2//Ministerio de Economía, Industria y Competitividad, Gobierno de España/ ; }, mesh = {Acoustics ; Age Factors ; Aging/*physiology ; Animals ; Deer/*physiology ; Female ; Vocalization, Animal/*physiology ; }, abstract = {OBJECTIVES: Studying animal vocal aging has potential implication in the field of animal welfare and for modeling human voice aging. The objective was to examine, using a repeated measures approach, the between-year changes of weight, social discomfort score (bites of other hinds on hind pelt), body condition score (fat reserves) and acoustic variables of the nasal (closed-mouth) and the oral (open-mouth) contact calls produced by farmed red deer hinds (Cervus elaphus) toward their young.

RESULTS: Repeated measures ANOVA revealed that with an increase of hind age for 1 year, the acoustic variables of their nasal contact calls (the beginning and maximum fundamental frequencies, the depth of frequency modulation and the peak frequency) decreased, whereas in their oral contact calls only the end fundamental frequency decreased. Duration and power quartiles did not change in any call type. Body weight and body condition score increased between years, whereas discomfort score decreased. Results of this study revealed directly the short-term effects of aging on the acoustics of the nasal contact calls in the same hinds. This study also confirmed that elevated emotional arousal during emission of the oral contact masks the effects of aging on vocalization in female red deer.}, } @article {pmid30333060, year = {2018}, author = {Zemicheal, G and Mekonnen, Y}, title = {Antiplasmodial activity of Vernonia adoensis aqueous, methanol and chloroform leaf extracts against chloroquine sensitive strain of Plasmodium berghei in vivo in mice.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {736}, pmid = {30333060}, issn = {1756-0500}, mesh = {Animals ; Antiprotozoal Agents/administration & dosage/pharmacokinetics/*pharmacology ; Chloroform ; Disease Models, Animal ; Dose-Response Relationship, Drug ; Ethiopia ; Malaria/*drug therapy ; Methanol ; Mice ; Parasitemia/*drug therapy ; Plant Extracts/administration & dosage/pharmacokinetics/*pharmacology ; Plant Leaves ; Plasmodium berghei/*drug effects ; *Vernonia ; Water ; }, abstract = {OBJECTIVE: The aim of this study was to investigate the antiplasmodial effects of the crude aqueous, methanol and chloroform extracts of the leaves of Vernonia adoensis in Plasmodium berghei infected Swiss albino mice using Peters' 4-day suppressive test.

RESULTS: The number of mice used for the toxicity test was 20 (5/group) and for each extract and control groups 5 mice per group was used. The aqueous, methanol and chloroform extracts of V. adoensis leaves indicated statistically significant (P < 0.05) suppression of parasitaemia in the treated mice. The highest inhibition was that of the methanol extract treated mice (83.36%) followed by aqueous (72.26%) and chloroform (54.34%) at an oral dose of 600 mg/kg b.wt. Each extract prevented body weight loss and packed cell volume (PCV) reduction as compared to the negative control groups. The survival time of the mice treated with chloroform based on Kaplan-Meir analysis was 12.53 ± 0.37 at 600 mg/kg b.wt, while the negative control was 7.93 ± 0.37 days. The LD50 of the extracts was greater than 3000 mg/kg body weight. In conclusion, the crude leaves extract of V. adoensis have demonstrated antiplasmodial effect in vivo. P. berghei infection is suppressed in a dose-dependent manner showing relevance of the traditional use of the plant.}, } @article {pmid30333053, year = {2018}, author = {Takele, WW and Alemayehu, M and Derso, T and Tariku, A}, title = {Two-thirds of pregnant women attending antenatal care clinic at the University of Gondar Hospital are found with subclinical iodine deficiency, 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {738}, pmid = {30333053}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Hospitals, University ; Humans ; Iodine/deficiency/*metabolism/urine ; Middle Aged ; Pregnancy ; Pregnancy Complications/epidemiology/*metabolism/urine ; Prenatal Care ; Young Adult ; }, abstract = {OBJECTIVE: This study was aimed at determining the magnitude of prenatal iodine deficiency and its determinants among women attending antenatal care clinic at the University of Gondar Specialized Referral Hospital, Northwest Ethiopia. A cross-sectional study was conducted from March 13 to April 25/2017. Precisely, 378 pregnant women were included in the study selected via systematic random sampling technique. Urinary Iodine concentration was determined through spectrophotometer using Sandell-Kolthoff reaction. Iodine deficiency was defined as women having urinary iodine concentration of < 150 µg/L. Moreover, stool examination was done.

RESULTS: Subclinical iodine deficiency among pregnant women was 60.5% (95% CI 55%, 65.5%). The Median iodine concentration was 137 μg/L (IQR 80 μg/L). Being governmental employee [AOR = 0.42 (95% CI 0.1 = 20, 0.87)], cabbage consumption of twice or more times per week [AOR = 2.35 (95% CI 1.44, 3.82)], not consuming maize in the last 1 week [AOR = 0.29 (95% CI 0.18, 0.48)], poor household wealth status [AOR = 2.7 (95% CI 1.24, 5.89)], and second trimester of pregnancy [AOR = 2.43 (95% CI 1.37, 4.32)] were significantly associated with iodine deficiency. Prenatal iodine deficiency was high, which deemed a mild public Health problem. Therefore, improving household income, and nutrition education to minimize maize and cabbage consumption are recommended.}, } @article {pmid30333051, year = {2018}, author = {Fahimipour, AK and Hartmann, EM and Siemens, A and Kline, J and Levin, DA and Wilson, H and Betancourt-Román, CM and Brown, GZ and Fretz, M and Northcutt, D and Siemens, KN and Huttenhower, C and Green, JL and Van Den Wymelenberg, K}, title = {Daylight exposure modulates bacterial communities associated with household dust.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {175}, pmid = {30333051}, issn = {2049-2618}, support = {P50 GM098911/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Microbial communities associated with indoor dust abound in the built environment. The transmission of sunlight through windows is a key building design consideration, but the effects of light exposure on dust communities remain unclear. We report results of an experiment and computational models designed to assess the effects of light exposure and wavelengths on the structure of the dust microbiome. Specifically, we placed household dust in replicate model "rooms" with windows that transmitted visible, ultraviolet, or no light and measured taxonomic compositions, absolute abundances, and viabilities of the resulting bacterial communities.

RESULTS: Light exposure per se led to lower abundances of viable bacteria and communities that were compositionally distinct from dark rooms, suggesting preferential inactivation of some microbes over others under daylighting conditions. Differences between communities experiencing visible and ultraviolet light wavelengths were relatively minor, manifesting primarily in abundances of dead human-derived taxa. Daylighting was associated with the loss of a few numerically dominant groups of related microorganisms and apparent increases in the abundances of some rare groups, suggesting that a small number of microorganisms may have exhibited modest population growth under lighting conditions. Although biological processes like population growth on dust could have generated these patterns, we also present an alternate statistical explanation using sampling models from ecology; simulations indicate that artefactual, apparent increases in the abundances of very rare taxa may be a null expectation following the selective inactivation of dominant microorganisms in a community.

CONCLUSIONS: Our experimental and simulation-based results indicate that dust contains living bacterial taxa that can be inactivated following changes in local abiotic conditions and suggest that the bactericidal potential of ordinary window-filtered sunlight may be similar to ultraviolet wavelengths across dosages that are relevant to real buildings.}, } @article {pmid30333050, year = {2018}, author = {Gamboa, OA and Agudelo, SI and Maldonado, MJ and Leguizamón, DC and Cala, SM}, title = {Evaluation of two strategies for debriefing simulation in the development of skills for neonatal resuscitation: a randomized clinical trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {739}, pmid = {30333050}, issn = {1756-0500}, mesh = {Adult ; Asphyxia Neonatorum/*therapy ; Cardiopulmonary Resuscitation/*methods ; *Clinical Competence ; Female ; Hospitals, University ; Humans ; Infant, Newborn ; Intensive Care, Neonatal/*methods ; Male ; Meconium Aspiration Syndrome/*therapy ; Middle Aged ; Patient Care Team ; Personnel, Hospital/*education ; Respiratory Distress Syndrome, Newborn/*therapy ; Simulation Training/*methods ; Single-Blind Method ; Video Recording ; }, abstract = {OBJECTIVE: To evaluate two debriefing strategies for the development of neonatal resuscitation skills in health professionals responsible for the critical newborn care in a high-complexity university Hospital.

RESULTS: A simple blind randomized clinical trial was conducted. Twenty-four professionals (pediatricians, nurses, and respiratory therapists) were randomly assigned for two interventions; one group received oral debriefing and the other oral debriefing assisted by video. Three standardized clinical scenarios that were recorded on video were executed. A checklist was applied for the evaluation, administered by a reviewer blinded to the assignment of the type of debriefing. The two debriefing strategies increased the technical and behavioral neonatal resuscitation skills of the participants, without one being superior to the other. The coefficient of the difference in the compliance percentage between the two types of debriefing was - 3.6% (95% CI - 13.77% to 6.47%). When comparing the development of technical and behavioral skills among the professionals evaluated, no significant differences were found between the types of debriefing. The two debriefing strategies increase compliance percentages, reaching or approaching 100%. Trial Registration ClinicalTrials.gov NCT03606278. July 30, 2018. Retrospectively registered.}, } @article {pmid30333045, year = {2018}, author = {Devenney, LE and Coyle, KB and Verster, JC}, title = {The impact of expectancy on cognitive performance during alcohol hangover.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {730}, pmid = {30333045}, issn = {1756-0500}, mesh = {Adult ; Alcoholic Intoxication/complications/*physiopathology ; Anticipation, Psychological/drug effects/*physiology ; Attention/drug effects/*physiology ; Executive Function/drug effects/*physiology ; Female ; Humans ; Male ; Memory, Short-Term/drug effects/*physiology ; Psychomotor Performance/drug effects/*physiology ; Young Adult ; }, abstract = {OBJECTIVE: Knowing the purpose of a clinical study may provoke expectancies among subjects that may influence the study outcome. For example, expectancies about a drug effect may cause subjects to put in more effort to counteract these effects on performance tasks, or cause stress or other mood alterations in anticipation of expected adverse effects. The objective of this study was to investigate to what extent expectancy effects will influence the magnitude of cognitive performance decrement in the alcohol hangover state.

RESULTS: Forty subjects with a mean (SD) age of 24.0 (7.4) years old participated in a naturalistic study to examine the alcohol hangover effects on cognitive performance. Subjects in the expectancy group were informed of the purpose of the study. In the control group subjects were told that the purpose of the study was to investigate the effects of time of day on cognitive performance. Subjects consumed a mean (SD) of 12.9 (10.0) alcoholic drinks the night before testing. Cognitive tests included the Stroop test, Eriksen's flanker test, a divided attention test, intra-extra dimensional set shifting test, spatial working memory test, and free word recall test. Expectancy effects did not differentially affect cognitive performance in the alcohol hangover state.}, } @article {pmid30333010, year = {2018}, author = {Du, P and Li, L and Liu, H and Fu, L and Qin, L and Zhang, Z and Cui, C and Sun, Z and Han, S and Xu, J and Dai, X and Huang, B and Dong, W and Tang, F and Zhuang, L and Han, Y and Qi, Z and Zhang, X}, title = {High-resolution chromosome painting with repetitive and single-copy oligonucleotides in Arachis species identifies structural rearrangements and genome differentiation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {240}, pmid = {30333010}, issn = {1471-2229}, support = {CARS-13//the China Agriculture Research System/ ; S2012-05//the Henan Provincial Agriculture Research System, China/ ; 161100111000//the Major Technology Research and Development Program of Henan Province, China/ ; }, mesh = {Arachis/*genetics ; Chromosome Painting ; Chromosomes, Plant/*genetics ; DNA, Ribosomal ; *Gene Rearrangement ; Genome, Plant/*genetics ; In Situ Hybridization, Fluorescence ; Karyotyping ; Molecular Probes ; Oligonucleotides ; Repetitive Sequences, Nucleic Acid/genetics ; }, abstract = {BACKGROUND: Arachis contains 80 species that carry many beneficial genes that can be utilized in the genetic improvement of peanut (Arachis hypogaea L. 2n = 4x = 40, genome AABB). Chromosome engineering is a powerful technique by which these genes can be transferred and utilized in cultivated peanut. However, their small chromosomes and insufficient cytological markers have made chromosome identification and studies relating to genome evolution quite difficult. The development of efficient cytological markers or probes is very necessary for both chromosome engineering and genome discrimination in cultivated peanut.

RESULTS: A simple and efficient oligonucleotide multiplex probe to distinguish genomes, chromosomes, and chromosomal aberrations of peanut was developed based on eight single-stranded oligonucleotides (SSONs) derived from repetitive sequences. High-resolution karyotypes of 16 Arachis species, two interspecific F1 hybrids, and one radiation-induced M1 plant were then developed by fluorescence in situ hybridization (FISH) using oligonucleotide multiplex, 45S and 5S rDNAs, and genomic in situ hybridization (GISH) using total genomic DNA of A. duranensis (2n = 2x = 20, AA) and A. ipaënsis (2n = 2x = 20, BB) as probes. Genomes, chromosomes, and aberrations were clearly identifiable in the established karyotypes. All eight cultivars had similar karyotypes, whereas the eight wild species exhibited various chromosomal variations. In addition, a chromosome-specific SSON library was developed based on the single-copy sequence of chromosome 6A of A. duranensis. In combination with repetitive SSONs and rDNA FISH, the single-copy SSON library was applied to identify the corresponding A3 chromosome in the A. duranensis karyotype.

CONCLUSIONS: The development of repetitive and single-copy SSON probes for FISH and GISH provides useful tools for the differentiation of chromosomes and identification of structural chromosomal rearrangement. It facilitates the development of high-resolution karyotypes and detection of chromosomal variations in Arachis species. To our knowledge, the methodology presented in this study demonstrates for the first time the correlation between a sequenced chromosome region and a cytologically identified chromosome in peanut.}, } @article {pmid30332993, year = {2018}, author = {Zhang, B and Zhang, X and Liu, G and Guo, L and Qi, T and Zhang, M and Li, X and Wang, H and Tang, H and Qiao, X and Pei, W and Shahzad, K and Xing, C and Zhang, J and Wu, J}, title = {A combined small RNA and transcriptome sequencing analysis reveal regulatory roles of miRNAs during anther development of Upland cotton carrying cytoplasmic male sterile Gossypium harknessii (D2) cytoplasm.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {242}, pmid = {30332993}, issn = {1471-2229}, support = {2016YFD0101400//National Key Research and Development program of China/ ; 31621005//National Natural Science Foundation of China/ ; }, mesh = {Cytoplasm/metabolism ; Flowers/cytology/genetics/growth & development ; Gene Expression Regulation, Plant ; Gene Library ; Gene Ontology ; Gossypium/cytology/*genetics/growth & development ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; Plant Infertility/*genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Cytoplasmic male sterility (CMS) in flowering plants is usually caused by incompatibility between mitochondrial and nuclear genomes, and can be restored by nuclear genes known as restorer-of-fertility (Rf). Although the CMS/Rf system is useful and convenient for economic production of commercial hybrid seed, the molecular mechanisms of CMS occurrence and fertility restoration in cotton are unclear.

RESULTS: Here, a combined small RNA and transcriptome sequencing analysis was performed on floral buds at the meiosis stage in three-line hybrid cotton system, and differentially expressed microRNAs (DEMs) and their target genes were identified and further analyzed for a possible involvement in CMS and fertility restoration. Totally 10 and 30 differentially expressed miRNA-target gene pairs were identified in A-B and A-R comparison group, respectively. A putative regulatory network of CMS occurrence and fertility restoration-related miRNA-target pairs during anther development were then constructed. The RLM-RACE analysis showed that gra-miR7505b regulates a PPR gene (Gh_D05G3392) by cleaving precisely at the 643 nt and 748 nt sites. The further analysis indicated that the sequence variation in the binding regions of Gh_D05G3392 and Gh_D05G3356 may cause a lower cleavage efficiency of the PPR genes by miR7505b and miR7505 in R line, respectively, leading to the up-regulation of the PPR genes and fertility restoration. These results have established their genetic involvement in fertility restoration in the CMS-D2 system.

CONCLUSION: Our combined miRNA and transcriptome analysis in three-line hybrid cotton system provides new insights into the molecular mechanisms of CMS occurrence and fertility restoration, which will contribute to further hybrid breeding in cotton.}, } @article {pmid30332991, year = {2018}, author = {Song, H and Sun, W and Yang, G and Sun, J}, title = {WRKY transcription factors in legumes.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {243}, pmid = {30332991}, issn = {1471-2229}, mesh = {Evolution, Molecular ; Fabaceae/*genetics ; Phylogeny ; Plant Proteins/genetics ; Protein Domains ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: WRKY transcription factors, so named because of the WRKYGQK heptapeptide at the N-terminal end, are widely distributed in plants and play an important role in physiological changes and response to biotic and abiotic stressors. Many previous studies have focused on the evolution of WRKY transcription factors in a given plant; however, little is known about WRKY evolution in legumes. The gene expression pattern of duplicated WRKY transcription factors remains unclear.

RESULTS: We first identified the WRKY proteins in 12 legumes. We found that the WRKYGQK heptapeptide tended to mutate into WRKYGKK. The Q site in WRKYGQK preferentially mutated, while W, K, and Y were conserved. The phylogenetic tree shows that the WRKY proteins in legumes have multiple origins, especially group IIc. For example, WRKY64 from Lupinus angustifolius (LaWRKY64) contains three WRKY domains, of which the first two clustered together in the N-terminal WRKY domain of the group I WRKY protein, and the third WRKY domain grouped in the C-terminal WRKY domain of the group I WRKY protein. Orthologous WRKY genes have a faster evolutionary rate and are subject to constrained selective pressure, unlike paralogous WRKY genes. Different gene features were observed between duplicated WRKY genes and singleton WRKY genes. Duplicated Glycine max WRKY genes with similar gene features have gene expression divergence.

CONCLUSIONS: We analyzed the WRKY number and type in 12 legumes, concluding that the WRKY proteins have multiple origins. A novel WRKY protein, LaWRKY64, was found in L. angustifolius. The first two WRKY domains of LaWRKY64 have the same origin. The orthologous and paralogous WRKY proteins have different evolutionary rates. Duplicated WRKY genes have gene expression divergence under normal growth conditions in G. max. These results provide insight into understanding WRKY evolution and expression.}, } @article {pmid30332990, year = {2018}, author = {Mahé, P and Tournoud, M}, title = {Predicting bacterial resistance from whole-genome sequences using k-mers and stability selection.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {383}, pmid = {30332990}, issn = {1471-2105}, mesh = {*Algorithms ; Anti-Bacterial Agents/pharmacology ; Base Sequence ; Databases, Genetic ; Drug Resistance, Bacterial/drug effects/*genetics ; *Genome, Bacterial ; Logistic Models ; Models, Genetic ; Mycobacterium tuberculosis/drug effects/*genetics ; ROC Curve ; Reproducibility of Results ; Staphylococcus aureus/drug effects/*genetics ; *Whole Genome Sequencing ; }, abstract = {BACKGROUND: Several studies demonstrated the feasibility of predicting bacterial antibiotic resistance phenotypes from whole-genome sequences, the prediction process usually amounting to detecting the presence of genes involved in antibiotic resistance mechanisms, or of specific mutations, previously identified from a training panel of strains, within these genes. We address the problem from the supervised statistical learning perspective, not relying on prior information about such resistance factors. We rely on a k-mer based genotyping scheme and a logistic regression model, thereby combining several k-mers into a probabilistic model. To identify a small yet predictive set of k-mers, we rely on the stability selection approach (Meinshausen et al., J R Stat Soc Ser B 72:417-73, 2010), that consists in penalizing logistic regression models with a Lasso penalty, coupled with extensive resampling procedures.

RESULTS: Using public datasets, we applied the resulting classifiers to two bacterial species and achieved predictive performance equivalent to state of the art. The models are extremely sparse, involving 1 to 8 k-mers per antibiotic, hence are remarkably easy and fast to evaluate on new genomes (from raw reads to assemblies).

CONCLUSION: Our proof of concept therefore demonstrates that stability selection is a powerful approach to investigate bacterial genotype-phenotype relationships.}, } @article {pmid30332989, year = {2018}, author = {Wang, M and Ji, Y and Feng, S and Liu, C and Xiao, Z and Wang, X and Wang, Y and Xia, G}, title = {The non-random patterns of genetic variation induced by asymmetric somatic hybridization in wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {244}, pmid = {30332989}, issn = {1471-2229}, support = {2016YFD0102003//National Key Research and Development Project/ ; 31171175//National Natural Science Foundation of China/ ; 31430060//National Natural Science Foundation of China/ ; }, mesh = {Chromatin/genetics ; Expressed Sequence Tags ; *Genetic Variation ; INDEL Mutation ; Sequence Deletion ; Triticum/*genetics ; }, abstract = {BACKGROUND: Asymmetric somatic hybridization is an efficient crop breeding approach by introducing several exogenous chromatin fragments, which leads to genomic shock and therefore induces genome-wide genetic variation. However, the fundamental question concerning the genetic variation such as whether it occurs randomly and suffers from selection pressure remains unknown.

RESULTS: Here, we explored this issue by comparing expressed sequence tags of a common wheat cultivar and its asymmetric somatic hybrid line. Both nucleotide substitutions and indels (insertions and deletions) had lower frequencies in coding sequences than in un-translated regions. The frequencies of nucleotide substitutions and indels were both comparable between chromosomes with and without introgressed fragments. Nucleotide substitutions distributed unevenly and were preferential to indel-flanking sequences, and the frequency of nucleotide substitutions at 5'-flanking sequences of indels was obviously higher in chromosomes with introgressed fragments than in those without exogenous fragment. Nucleotide substitutions and indels both had various frequencies among seven groups of allelic chromosomes, and the frequencies of nucleotide substitutions were strongly negatively correlative to those of indels. Among three sets of genomes, the frequencies of nucleotide substitutions and indels were both heterogeneous, and the frequencies of nucleotide substitutions exhibited drastically positive correlation to those of indels.

CONCLUSIONS: Our work demonstrates that the genetic variation induced by asymmetric somatic hybridization is attributed to both whole genomic shock and local chromosomal shock, which is a predetermined and non-random genetic event being closely associated with selection pressure. Asymmetric somatic hybrids provide a worthwhile model to further investigate the nature of genomic shock induced genetic variation.}, } @article {pmid30332988, year = {2018}, author = {Sun, Y and Luo, W and Jain, A and Liu, L and Ai, H and Liu, X and Feng, B and Zhang, L and Zhang, Z and Guohua, X and Sun, S}, title = {OsPHR3 affects the traits governing nitrogen homeostasis in rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {241}, pmid = {30332988}, issn = {1471-2229}, support = {31672226//Chinese National Natural Science Foundation/ ; 2016yfd0100700//National Key Research and Development Program of China/ ; 2016ZX08009-003-005//National Program on R&D of Transgenic Plants/ ; BK20141367//Natural Science Foundation of Jiangsu Province (CN)/ ; IRT1256//Innovative Research Team Development Plan of the Ministry of Education/ ; 12009//111 Project/ ; }, mesh = {Arabidopsis/genetics/physiology ; Homeostasis ; Mutation ; Nitrogen/*metabolism ; Oryza/*genetics/physiology ; Phenotype ; Phosphates/*metabolism ; Plant Proteins/genetics/metabolism ; Seeds/genetics ; Signal Transduction ; Transcription Factors/genetics/*metabolism ; }, abstract = {BACKGROUND: Phosphate (Pi) and Nitrogen (N) are essential macronutrients required for plant growth and development. In Arabidopsis thaliana (Arabidopsis), the transcription factor PHR1 acts as a Pi central regulator. PHL1 is a homolog of PHR1 and also plays a role in maintaining Pi homeostasis. In rice (Oryza sativa), OsPHR1-4 are the orthologs of PHR1 and have been implicated in regulating sensing and signaling cascades governing Pi homeostasis.

RESULTS: Here the role of OsPHR3 was examined in regulating the homeostasis of N under different Pi regimes. Deficiencies of different variants of N exerted attenuating effects on the relative expression levels of OsPHR3 in a tissue-specific manner. For the functional characterization of OsPHR3, its Tos17 insertion homozygous mutants i.e., osphr3-1, osphr3-2, and osphr3-3 were compared with the wild-type for various morphophysiological and molecular traits during vegetative (hydroponics with different regimes of N variants) and reproductive (pot soil) growth phases. During vegetative growth phase, compared with the wild-type, OsPHR3 mutants showed significant variations in the adventitious root development, influx rates of 15N-NO3- and 15N-NH4+, concentrations of total N, NO3- and NH4+ in different tissues, and the relative expression levels of OsNRT1.1a, OsNRT2.4, OsAMT1;1, OsNia1 and OsNia2. The effects of the mutation in OsPHR3 was also explicit on the seed-set and grain yield during growth in a pot soil. Although Pi deficiency affected total N and NO3- concentration, the lateral root development and the relative expression levels of some of the NO3- and NH4+ transporter genes, its availability did not exert any notable regulatory influences on the traits governing N homeostasis.

CONCLUSIONS: OsPHR3 plays a pivotal role in regulating the homeostasis of N independent of Pi availability.}, } @article {pmid30332987, year = {2018}, author = {Tang, J and Liang, Y and Jiang, D and Li, L and Luo, Y and Shah, MMR and Daroch, M}, title = {Temperature-controlled thermophilic bacterial communities in hot springs of western Sichuan, China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {134}, pmid = {30332987}, issn = {1471-2180}, support = {31550110497//National Natural Science Foundation of China/ ; JCYJ20160122151433832//Shenzhen Municipal Government/ ; 2081917012//Chengdu University/ ; }, abstract = {BACKGROUND: Ganzi Prefecture in Western China is situated geographically at the transition regions between Tibetan Plateau and Sichuan Basin in a highly tectonically active boundary area between the India and Eurasia plates. The region hosts various hot springs that span a wide range of temperature from 30 to 98 °C and are located at high altitude (up to 4200 m above sea level) in the region of large geothermal anomalies and active Xianshuihe slip-fault that has been active since Holocene. The site represents a biodiversity reservoir for thermophiles, yet their diversity and relationship to geochemical parameters are largely unknown. In the present work, bacterial diversity and community structure in 14 hot springs of Ganzi were investigated using Illumina MiSeq sequencing.

RESULTS: Bacterial community compositions were evidently distinct among the 14 hot springs, and the bacterial communities in hot springs were majorly abundant in phyla Aquificae, Cyanobacteria and Proteobacteria. Both clustering and PCoA analysis suggested the existence of four bacterial community patterns in these hot springs. Temperature contributed to shaping bacterial community structure of hot springs as revealed by correlation analysis. Abundant unassigned-genus sequences detected in this study strongly implied the presence of novel genera or genetic resources in these hot springs.

CONCLUSION: The diversity of hot springs of Ganzi prefecture in Western Sichuan, China is evidently shaped by temperature. Interestingly disproportionally abundant unassigned-genus sequences detected in this study show indicate potential of novel genera or phylotypes. We hypothesize that frequent earthquakes and rapidly changing environment might have contributed to evolution of these potentially new lineages. Overall, this study provided first insight into the bacterial diversity of hot springs located in Western Sichuan, China and its comparison with other similar communities worldwide.}, } @article {pmid30332986, year = {2018}, author = {Kosoltanapiwat, N and Reamtong, O and Okabayashi, T and Ampawong, S and Rungruengkitkun, A and Thiangtrongjit, T and Thippornchai, N and Leaungwutiwong, P and Mahittikorn, A and Mori, H and Yoohanngoa, T and Yamwong, P}, title = {Mass spectrometry-based identification and whole-genome characterisation of the first pteropine orthoreovirus isolated from monkey faeces in Thailand.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {135}, pmid = {30332986}, issn = {1471-2180}, abstract = {BACKGROUND: The pteropine orthoreovirus (PRV) was isolated from monkey (Macaca fascicularis) faecal samples collected from human-inhabited areas in Lopburi Province, Thailand. These samples were initially obtained to survey for the presence of hepatitis E virus (HEV).

RESULTS: Two virus isolates were retrieved by virus culture of 55 monkey faecal samples. Liquid chromatography-tandem mass spectrometry (LC-MS/MS) was successfully used to identify the viruses as the segmented dsRNA orthoreovirus. Phylogenetic analysis of the Lopburi orthoreovirus whole-genomes revealed relationships with the well-characterised PRVs Pulau (segment L1), Cangyuan (segments L2, M3 and S3), Melaka (segments L3 and M2), Kampar (segments M1 and S2) and Sikamat (segments S1 and S4) of Southeast Asia and China with nucleotide sequence identities of 93.5-98.9%. RT-PCR showed that PRV was detected in 10.9% (6/55) and HEV was detected in 25.5% (14/55) of the monkey faecal samples.

CONCLUSIONS: PRV was isolated from monkey faeces for the first time in Thailand via viral culture and LC-MS/MS. The genetic diversity of the virus genome segments suggested a re-assortment within the PRV species group. The overall findings emphasise that monkey faeces can be sources of zoonotic viruses, including PRV and HEV, and suggest the need for active virus surveillance in areas of human and monkey co-habitation to prevent and control emerging zoonotic diseases in the future.}, } @article {pmid30332983, year = {2018}, author = {Bai, JF and Wang, YK and Wang, P and Yuan, SH and Gao, JG and Duan, WJ and Wang, N and Zhang, FT and Zhang, WJ and Qin, MY and Zhao, CP and Zhang, LP}, title = {Genome-wide identification and analysis of the COI gene family in wheat (Triticum aestivum L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {754}, pmid = {30332983}, issn = {1471-2164}, support = {2016YFD0101601//National Key Research Project/ ; 6182014//Natural Science Foundation of Beijing/ ; 2014BAD01B09//National Science and Technology Support Plan/ ; 31661143018//National Natural Science Foundation of China/ ; 31872881//National Natural Science Foundation of China/ ; GJHZ2018-1//International Cooperation Fund of Beijing Academy of Agricultural and Forestry Sciences/ ; }, mesh = {Cyclopentanes/metabolism ; Gene Expression Profiling ; Genome, Plant/genetics ; *Genomics ; Organ Specificity ; Oxylipins/metabolism ; Phylogeny ; Promoter Regions, Genetic/genetics ; Signal Transduction/genetics ; Triticum/cytology/*enzymology/*genetics ; Ubiquitin-Protein Ligases/*genetics ; }, abstract = {BACKGROUND: COI (CORONATINE INSENSITIVE), an F-box component of the Skp1-Cullin-F-box protein (SCFCOI1) ubiquitin E3 ligase, plays important roles in the regulation of plant growth and development. Recent studies have shown that COIs are involved in pollen fertility. In this study, we identified and characterized COI genes in the wheat genome and analyzed expression patterns under abiotic stress.

RESULTS: A total of 18 COI candidate sequences for 8 members of COI gene family were isolated in wheat (Triticum aestivum L.). Phylogenetic and structural analyses showed that these COI genes could be divided into seven distinct subfamilies. The COI genes showed high expression in stamens and glumes. The qRT-PCR results revealed that wheat COIs were involved in several abiotic stress responses and anther/glume dehiscence in the photoperiod-temperature sensitive genic male sterile (PTGMS) wheat line BS366.

CONCLUSIONS: The structural characteristics and expression patterns of the COI gene family in wheat as well as the stress-responsive and differential tissue-specific expression profiles of each TaCOI gene were examined in PTGMS wheat line BS366. In addition, we examined SA- and MeJA-induced gene expression in the wheat anther and glume to investigate the role of COI in the JA signaling pathway, involved in the regulation of abnormal anther dehiscence in the PTGMS wheat line. The results of this study contribute novel and detailed information about the TaCOI gene family in wheat and could be used as a benchmark for future studies of the molecular mechanisms of PTGMS in other crops.}, } @article {pmid30332609, year = {2018}, author = {Range, RC}, title = {Canonical and non-canonical Wnt signaling pathways define the expression domains of Frizzled 5/8 and Frizzled 1/2/7 along the early anterior-posterior axis in sea urchin embryos.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {83-92}, doi = {10.1016/j.ydbio.2018.10.003}, pmid = {30332609}, issn = {1095-564X}, support = {R15 HD088272/HD/NICHD NIH HHS/United States ; }, abstract = {The spatiotemporal expression of Frizzled receptors is critical for patterning along the early anterior-posterior axis during embryonic development in many animal species. However, the molecular mechanisms that regulate the expression of Frizzled receptors are incompletely understood in any species. In this study, I examine how the expression of two Frizzled receptors, Fzl1/2/7 and Fzl5/8, is controlled by the Wnt signaling network which directs specification and positioning of early regulatory states along the anterior-posterior (AP) axis of sea urchin embryos. I used a combination of morpholino- and dominant negative-mediated interference to knock down each Wnt signaling pathway involved in the AP Wnt signaling network. I found that the expression of zygotic fzl5/8 as well as that of the anterior neuroectoderm gene regulatory network (ANE GRN) is activated by an unknown broadly expressed regulatory state and that posterior Wnt/β-catenin signaling is necessary to down regulate fzl5/8's expression in posterior blastomeres. I show that zygotic expression of fzl1/2/7 in the equatorial ectodermal belt is dependent on an uncharacterized regulatory mechanism that works in the same cells receiving the TGF-β signals patterning this territory along the dorsal-ventral axis. In addition, my data indicate that Fzl1/2/7 signaling represses its own expression in a negative feedback mechanism. Finally, we discovered that a balance between the activities of posterior Wnt8 and anterior Dkk1 is necessary to establish the correct spatial expression of zygotic fzl12/7 expression in the equatorial ectodermal domain during blastula and gastrula stages. Together, these studies lead to a better understanding of the complex interactions among the three Wnt signaling pathway governing AP axis specification and patterning in sea urchin embryos.}, } @article {pmid30332588, year = {2018}, author = {Passy, SI and Larson, CA and Jamoneau, A and Budnick, W and Heino, J and Leboucher, T and Tison-Rosebery, J and Soininen, J}, title = {Biogeographical Patterns of Species Richness and Abundance Distribution in Stream Diatoms Are Driven by Climate and Water Chemistry.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {605-617}, doi = {10.1086/699830}, pmid = {30332588}, issn = {1537-5323}, abstract = {In this intercontinental study of stream diatoms, we asked three important but still unresolved ecological questions: (1) What factors drive the biogeography of species richness and species abundance distribution (SAD)? (2) Are climate-related hypotheses, which have dominated the research on the latitudinal and altitudinal diversity gradients, adequate in explaining spatial biotic variability? and (3) Is the SAD response to the environment independent of richness? We tested a number of climatic theories and hypotheses (i.e., the species-energy theory, the metabolic theory, the energy variability hypothesis, and the climatic tolerance hypothesis) but found no support for any of these concepts, as the relationships of richness with explanatory variables were nonexistent, weak, or unexpected. Instead, we demonstrated that diatom richness and SAD evenness generally increased with temperature seasonality and at mid- to high total phosphorus concentrations. The spatial patterns of diatom richness and the SAD-mainly longitudinal in the United States but latitudinal in Finland-were defined primarily by the covariance of climate and water chemistry with space. The SAD was not entirely controlled by richness, emphasizing its utility for ecological research. Thus, we found support for the operation of both climate and water chemistry mechanisms in structuring diatom communities, which underscores their complex response to the environment and the necessity for novel predictive frameworks.}, } @article {pmid30332587, year = {2018}, author = {Groner, ML and Shields, JD and Landers, DF and Swenarton, J and Hoenig, JM}, title = {Rising Temperatures, Molting Phenology, and Epizootic Shell Disease in the American Lobster.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {E163-E177}, doi = {10.1086/699478}, pmid = {30332587}, issn = {1537-5323}, abstract = {Phenological mismatch-maladaptive changes in phenology resulting from altered timing of environmental cues-is an increasing concern in many ecological systems, yet its effects on disease are poorly characterized. American lobster (Homarus americanus) is declining at its southern geographic limit. Rising seawater temperatures are associated with seasonal outbreaks of epizootic shell disease (ESD), which peaks in prevalence in the fall. We used a 34-year mark-recapture data set to investigate relationships between temperature, molting phenology, and ESD in Long Island Sound, where temperatures are increasing at 0.4°C per decade. Our analyses support the hypothesis that phenological mismatch is linked to the epidemiology of ESD. Warming spring temperatures are correlated with earlier spring molting. Lobsters lose diseased cuticle by molting, and early molting increases the intermolt period in the summer, when disease prevalence is increasing to a fall peak. In juvenile and adult male lobsters, September ESD prevalence was correlated with early molting, while October ESD prevalence was correlated with summer seawater temperature. This suggests that temperature-induced molting phenology affects the timing of the onset of ESD, but later in the summer this signal is swamped by the stronger signal of summer temperatures, which we hypothesize are associated with an increased rate of new infections. October ESD prevalence was ∼80% in years with hot summers and ∼30% in years with cooler summers. Yearly survival of diseased lobsters is <50% that of healthy lobsters. Thus, population impacts of ESD are expected to increase with increasing seawater temperatures.}, } @article {pmid30332586, year = {2018}, author = {Ivimey-Cook, E and Moorad, J}, title = {Disentangling Pre- and Postnatal Maternal Age Effects on Offspring Performance in an Insect with Elaborate Maternal Care.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {564-576}, doi = {10.1086/699654}, pmid = {30332586}, issn = {1537-5323}, abstract = {Maternal effect senescence has attracted much recent scientific interest. However, the age-related effects of pre- and postnatal maternal age are often conflated, as these naturally originate from the same individual. Additionally, many maternal effect senescence studies fail to account for potential biases associated with selective disappearance. Here we use a cross-fostered laboratory population of a burying beetle, Nicrophorus vespilloides, to examine both the effects of female pre- and postnatal maternal age on offspring life-history traits and the postcare outcomes of mothers while accounting for selective disappearance of postnatal caregivers. Neither pre- nor postnatal maternal age affected offspring longevity or larval weight at hatching, and postnatal age had no effect on postcare maternal outcomes except to confirm the presence of actuarial senescence. There was weak evidence for concave relationships between two larval traits (dispersal weight and survival) and the age of egg producers. Selective disappearance of caregivers had no clear effect on any of the measured offspring traits. Contrary to predictions from evolutionary theory, maternal effect senescence and reproductive effort increases do not always manifest, and current theory may be insufficient to account for the true diversity of aging patterns relating to maternal care.}, } @article {pmid30332585, year = {2018}, author = {Cailleau, A and Grimanelli, D and Blanchet, E and Cheptou, PO and Lenormand, T}, title = {Dividing a Maternal Pie among Half-Sibs: Genetic Conflicts and the Control of Resource Allocation to Seeds in Maize.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {577-592}, doi = {10.1086/699653}, pmid = {30332585}, issn = {1537-5323}, abstract = {Resource allocation to offspring is the battleground for various intrafamilial conflicts. Understanding these conflicts requires knowledge of how the different actors (mother, siblings with different paternal genotypes) influence resource allocation. In angiosperms, allocation of resources to seeds happens postfertilization, and the paternally inherited genome in offspring can therefore influence resource allocation. However, the precise mode of resource allocation-and, in particular, the occurrence of sibling rivalry-has rarely been investigated in plants. In this article, we develop a new method for analyzing the resource-allocation traits of the different actors (maternal sporophyte and half-sibs) using data obtained from a large-scale diallel cross experiment in maize involving mixed hand pollination and color markers to assess seed weight of known paternity. We found strong evidence for the occurrence of sibling rivalry: resources invested in an ear were allocated competitively, and offspring with different paternal genotypes aggressively competed for these resources, entailing a measurable direct cost to the mother. We also show how resource allocation can be described for each genotype by two maternal traits (source effect, average sink responsiveness) and two offspring traits (ability to attract maternal resources, competitive ability toward siblings). We will discuss how these findings help to understand how genetic conflicts shape resource-allocation traits in angiosperms.}, } @article {pmid30332584, year = {2018}, author = {Zaguri, M and Zohar, Y and Hawlena, D}, title = {Considerations Used by Desert Isopods to Assess Scorpion Predation Risk.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {630-643}, doi = {10.1086/699840}, pmid = {30332584}, issn = {1537-5323}, abstract = {Animals adjust behaviors to balance changes in predation risk against other vital needs. Animals must therefore collect sensory information and use a complex risk-assessment process that estimates risks and weighs costs and benefits entailed in different reactions. Studying this cognitive process is challenging, especially in nature, because it requires inferring sensory abilities and conscious decisions from behavioral reactions. Our goal was to address this empirical challenge by implementing psychophysical principles to field research that explores considerations used by desert isopods (Hemilepistus reaumuri) to assess the risk of scorpions that hunt exclusively from within their burrows. We introduced various combinations of chemical and physical cues to the vicinity of isopod burrows and recorded their detailed reactions on first encountering the cues. The isopods reacted defensively to scorpion odor but only when accompanied with excavated soil or other odors typically found near scorpion burrows. Isopods also reacted defensively to piles of excavated soil without scorpion olfactory cues, suggesting that isopods take precautions even against physical disturbances that do not necessarily reflect predator activity. Simultaneous presence of different cues provoked graded responses, possibly reflecting an additive increase in risk estimation. We conclude that wild isopods use defensive reactions toward environmental signals only when the integrated perceptual information implies an active scorpion burrow or when they lack data to refute this possibility.}, } @article {pmid30332583, year = {2018}, author = {Merrill, L and Grindstaff, JL}, title = {Early Life Stress Strengthens Trait Covariance: A Plastic Response That Results in Reduced Flexibility.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {593-604}, doi = {10.1086/699839}, pmid = {30332583}, issn = {1537-5323}, abstract = {Stress exposure during development can impact both the expression of individual traits and associations between traits, but whether stress results in stronger or weaker associations between traits is unclear. In this study, we examined within- and among-trait associations for morphological and physiological traits in zebra finches (Taeniopygia guttata) exposed to corticosterone (CORT) during the nestling and fledging stages as well as in control birds. Birds exposed to CORT exhibited stronger within-trait correlations over time and stronger associations among traits. We found preliminary evidence that birds that died before the median age of death had stronger within- and among-trait correlations independent of treatment, and among CORT-treated birds, smaller birds were more likely to survive beyond the median age than larger birds. These findings suggest that stress hormone exposure in early life can result in reduced developmental flexibility, with potential fitness ramifications, and that these costs may be greater for larger offspring. Furthermore, our results provide experimental evidence for pleiotropic effects of hormones during development through altered patterns of phenotypic correlation.}, } @article {pmid30332582, year = {2018}, author = {Winbourne, JB and Harrison, MT and Sullivan, BW and Alvarez-Clare, S and Lins, SR and Martinelli, L and Nasto, M and Piotto, D and Rolim, S and Wong, M and Porder, S}, title = {A New Framework for Evaluating Estimates of Symbiotic Nitrogen Fixation in Forests.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {618-629}, doi = {10.1086/699828}, pmid = {30332582}, issn = {1537-5323}, abstract = {Symbiotic nitrogen fixation (SNF) makes atmospheric nitrogen biologically available and regulates carbon storage in many terrestrial ecosystems. Despite its global importance, estimates of SNF rates are highly uncertain, particularly in tropical forests where rates are assumed to be high. Here we provide a framework for evaluating the uncertainty of sample-based SNF estimates and discuss its implications for quantifying SNF and thus understanding of forest function. We apply this framework to field data sets from six lowland tropical rainforests (mature and secondary) in Brazil and Costa Rica. We use this data set to estimate parameters influencing SNF estimation error, notably the root nodule abundance and variation in SNF rates among soil cores containing root nodules. We then use simulations to gauge the relationship between sampling effort and SNF estimation accuracy for a combination of parameters. Field data illuminate a highly right-skewed lognormal distribution of SNF rates among soil cores containing root nodules that were rare and spanned five orders of magnitude. Consequently, simulations demonstrated that sample sizes of hundreds to even thousands of soil cores are needed to obtain estimates of SNF that are within, for example, a factor of 2 of the actual rate with 75% probability. This represents sample sizes that are larger than most studies to date. As a result of this previously undescribed uncertainty, we suggest that current estimates of SNF in tropical forests are not sufficiently constrained to elucidate forest stand-level controls of SNF, which hinders our understanding of the impact of SNF on tropical forest ecosystem processes.}, } @article {pmid30332581, year = {2018}, author = {Lichtenstein, JLL and Kamath, A and Bengston, S and Avilés, L and Pruitt, JN}, title = {Female-Biased Sex Ratios Increase Colony Survival and Reproductive Output in the Spider Anelosimus studiosus.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {552-563}, doi = {10.1086/699838}, pmid = {30332581}, issn = {1537-5323}, abstract = {Negative frequency-dependent selection acting on the sexes is hypothesized to drive populations toward a balanced sex ratio. However, numerous examples of female-biased sex ratios pepper the arthropods. Theoretical examinations have proposed that female-biased populations or groups can have higher chances of surviving and propagating that may be advantageous. We evaluated this hypothesis in the semisocial spider Anelosimus studiosus by creating artificial colonies of varying sex ratios and sizes and observing colony performance at sites with high versus low group extinction rates. We also tested whether colony extinction rates and sex ratios were correlated across 25 collection sites, spanning 10° latitude. We found that colonies with female-biased sex ratios produced more egg cases and were more likely to survive the duration of a field season, suggesting that female-biased sex ratios confer both survival and reproductive advantages on colonies. The effect of sex ratio on colony survival and reproductive output was strongest for small colonies in high extinction areas. Moreover, we found that female-biased sex ratios correlated with greater extinction rates across 25 sites, indicating that female-biased sex ratios may have evolved at some sites in response to high extinction rates. These findings suggest that selection favoring groups with female-biased sex ratios may operate in A. studiosus, shedding light on some of the factors that may drive the evolution of biased sex ratios.}, } @article {pmid30332580, year = {2018}, author = {Gerchen, JF and Dufresnes, C and Stöck, M}, title = {Introgression across Hybrid Zones Is Not Mediated by Large X-Effects in Green Toads with Undifferentiated Sex Chromosomes.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {E178-E188}, doi = {10.1086/699162}, pmid = {30332580}, issn = {1537-5323}, abstract = {Divergence between incipient species remains an incompletely understood process. Hybrid zones provide great research potential, reflecting natural organismal genomic interactions and gene evolution in a variety of recombinants over generations. While sex chromosomes are known evolutionary drivers of reproductive isolation, empirical population genetics has mostly examined species with heteromorphic sex chromosomes. We recently reported restricted introgression at sex-linked markers in an amphibian system with homomorphic sex chromosomes (Hyla), consistent with a large X-effect, designating a greater role of sex chromosomes in driving hybrid incompatibilities. Here, using a similar approach, we examined two hybrid zones of Palearctic green toads (Bufo viridis subgroup), involving several lineages that arose at different times and form secondary contacts. We find no evidence for differential introgression of sex-linked versus autosomal markers across both zones. This absence of large X-effects in Bufo indicates that, unlike in Hyla, hybrid incompatibilities may not result from the faster-heterogametic sex and faster-male aspects of Haldane's rule. The recent suppression of XY recombination in Hyla but not in Bufo may have driven greater divergence between Hyla sex chromosomes, causing stronger reproductive isolation. Alternatively, stronger linkage among Hyla's sex-linked markers could restrict introgression. We hypothesize that the degree of sex-specific recombination may condition the importance of homomorphic sex chromosomes in speciation.}, } @article {pmid30332579, year = {2018}, author = {Waser, NM and CaraDonna, PJ and Price, MV}, title = {Atypical Flowers Can Be as Profitable as Typical Hummingbird Flowers.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {644-653}, doi = {10.1086/699836}, pmid = {30332579}, issn = {1537-5323}, abstract = {In western North America, hummingbirds can be observed systematically visiting flowers that lack the typical reddish color, tubular morphology, and dilute nectar of "hummingbird flowers." Curious about this behavior, we asked whether these atypical flowers are energetically profitable for hummingbirds. Our field measurements of nectar content and hummingbird foraging speeds, taken over four decades at multiple localities, show that atypical flowers can be as profitable as typical ones and suggest that the profit can support 24-h metabolic requirements of the birds. Thus, atypical flowers may contribute to successful migration of hummingbirds, enhance their population densities, and allow them to occupy areas seemingly depauperate in suitable resources. These results illustrate what can be gained by attending to the unexpected.}, } @article {pmid30332578, year = {2018}, author = {Gibson, AK and Delph, LF and Vergara, D and Lively, CM}, title = {Periodic, Parasite-Mediated Selection For and Against Sex.}, journal = {The American naturalist}, volume = {192}, number = {5}, pages = {537-551}, doi = {10.1086/699829}, pmid = {30332578}, issn = {1537-5323}, abstract = {Asexual lineages should rapidly replace sexual populations. Why sex then? The Red Queen hypothesis proposes that parasite-mediated selection against common host genotypes could counteract the per capita birth rate advantage of asexuals. Under the Red Queen hypothesis, fluctuations in parasite-mediated selection can drive fluctuations in the asexual population, leading to the coexistence of sexual and asexual reproduction. Does shifting selection by parasites drive fluctuations in the fitness and frequency of asexuals in nature? Combining long-term field data with mesocosm experiments, we detected a shift in the direction of parasite selection in the snail Potamopyrgus antipodarum and its coevolving parasite, Microphallus sp. In the early 2000s, asexuals were more infected than sexuals. A decade later, the asexuals had declined in frequency and were less infected than sexuals. Over time, the mean infection prevalence of asexuals equaled that of sexuals but varied far more. This variation in asexual infection prevalence suggests the potential for parasite-mediated fluctuations in asexual fitness. Accordingly, we detected fitness consequences of the shift in parasite selection: when they were less infected than sexuals, asexuals increased in frequency in the field and in paired mesocosms that isolated the effect of parasites. The match between field and experiment argues that coevolving parasites drive temporal change in the relative fitness and frequency of asexuals, potentially promoting the coexistence of reproductive modes in P. antipodarum.}, } @article {pmid30329193, year = {2019}, author = {Noguera, JC}, title = {Crickets increase sexual signalling and sperm protection but live shorter in the presence of rivals.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {49-57}, doi = {10.1111/jeb.13390}, pmid = {30329193}, issn = {1420-9101}, support = {IJI-2014-20246//Ministerio de Economía y Competitividad/ ; IJI-2014-20246//Juan de la Cierva contract/ ; }, abstract = {The sociosexual environment animals experience through their life can shape the evolution of key life history traits, including longevity. Male-male competition, for instance, may influence the resources allocated to traits involved in male reproductive success. Here, I test whether lifelong exposure to a competitor male influences male investment in pre- and post-copulatory sexual traits (calling effort and sperm quality) and how this affected the oxidative status and longevity of male field crickets (Gryllus bimaculatus). As expected, the visual exposure to a mating competitor promoted a higher calling effort in the male crickets but resulted in a decline in the haemolymph antioxidant content. The haemolymph antioxidant content negatively covaried with the antioxidant content of the sperm but interestingly, only when the males were exposed to a competitor. This suggests that when mating competition is high, males may prioritize sperm antioxidant protection against somatic maintenance. Finally, I provide evidence that male-male competition imposes additional costs to reproduction, as males exposed to a mating competitor lost a significant proportion of body antioxidant defences and body mass over time and in long term, had a reduced lifespan. Overall, this study strongly suggests that intrasexual competition may impose additional oxidative costs during reproduction for males, with negative consequences on lifespan. Moreover, the results highlight the role of oxidative stress as a physiological mechanism underlying the trade-off between reproduction-longevity and through which sexual selection may contribute to the evolution of senescence patterns.}, } @article {pmid30328805, year = {2018}, author = {Li, Y and Zhang, Z and Xu, Z and Fang, D and Wang, ET and Shao, S and Du, Z and Liu, W and Xie, Z}, title = {Jeotgalibacillus proteolyticus sp. nov., a protease-producing bacterium isolated from ocean sediments.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3790-3795}, doi = {10.1099/ijsem.0.003060}, pmid = {30328805}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Peptide Hydrolases ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Planococcaceae/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, rod-shaped bacterial strain, 22-7T, was isolated from ocean sediment of Laizhou Bay, China, and was characterized by using a polyphasic approach. Optimal growth was observed at 33 °C on a 2216E agar plate of pH 7.5 and with 2 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences identified it as a member of the genus Jeotgalibacillus, most similar to Jeotgalibacillus campisalis SF-57T (98.7 % similarity), Jeotgalibacillus marinus DSM 1297T (98.2 %) and Jeotgalibacillus soli P9T (97.1 %). Average nucleotide identity values and digital DNA-DNA hybridization values were less than 74.2 and 18.1 %, respectively, between strain 22-7T and the type strains of closely related species. The major polar lipids were aminophospholipid, phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol; the major fatty acids (>10 %) were anteiso-C15 : 0 and iso-C15 : 0; and the major menaquinone was MK-7. The peptidoglycan type of the cell wall was A1α linked through l-lysine as the diamino acid. Combined data from phenotypic, chemotaxonomic and genotypic characterizations demonstrated that strain 22-7T represents a novel Jeotgalibacillus species, for which the name Jeotgalibacillus proteolyticus sp. nov. is proposed. The type strain is 22-7T(=MCCC 1H00228T=KCTC 33930T).}, } @article {pmid30328687, year = {2018}, author = {Wackett, LP}, title = {Web Alert: Pseudomonas (a tribute to Noberto Palleroni): An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3902-3903}, doi = {10.1111/1462-2920.14438}, pmid = {30328687}, issn = {1462-2920}, } @article {pmid30328239, year = {2018}, author = {McGenity, TJ}, title = {2038 - When microbes rule the Earth.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4213-4220}, doi = {10.1111/1462-2920.14449}, pmid = {30328239}, issn = {1462-2920}, } @article {pmid30328113, year = {2018}, author = {Watanabe, J}, title = {Clade-specific evolutionary diversification along ontogenetic major axes in avian limb skeleton.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2632-2652}, doi = {10.1111/evo.13627}, pmid = {30328113}, issn = {1558-5646}, abstract = {The evolutionary diversification of birds has been facilitated by specializations for various locomotor modes, with which the proportion of the limb skeleton is closely associated. However, recent studies have identified phylogenetic signals in this system, suggesting the presence of historical factors that have affected its evolutionary variability. In this study, to explore potential roles of ontogenetic integration in biasing the evolution in the avian limb skeleton, evolutionary diversification patterns in six avian families (Anatidae, Procellariidae, Ardeidae, Phalacrocoracidae, Laridae, and Alcidae) were examined and compared to the postnatal ontogenetic trajectories in those taxa, based on measurement of 2641 specimens and recently collected ontogenetic series, supplemented by published data. Morphometric analyses of lengths of six limb bones (humerus, ulna, carpometacarpus, femur, tibiotarsus, and tarsometatarsus) demonstrated that: (1) ontogenetic trajectories are diverse among families; (2) evolutionary diversification is significantly anisotropic; and, most importantly, (3) major axes of evolutionary diversification are correlated with clade-specific ontogenetic major axes in the shape space. These results imply that the evolutionary variability of the avian limbs has been biased along the clade-specific ontogenetic trajectories. It may explain peculiar diversification patterns characteristic to some avian groups, including the long-leggedness in Ardeidae and tendency for flightlessness in Anatidae.}, } @article {pmid30327830, year = {2018}, author = {Zhu, K and Ge, D and Wen, Z and Xia, L and Yang, Q}, title = {Evolutionary Genetics of Hypoxia and Cold Tolerance in Mammals.}, journal = {Journal of molecular evolution}, volume = {86}, number = {9}, pages = {618-634}, pmid = {30327830}, issn = {1432-1432}, support = {2014FY110100//National Special Fund on Basic Research of Science and Technology of China/ ; Y229YX5105//Key Laboratory of Zoological Systematics and Evolution of the Chinese Academy of Sciences/ ; }, abstract = {Low oxygen and fluctuant ambient temperature pose serious challenges to mammalian survival. Physiological adaptations in mammals to hypoxia and low temperatures have been intensively investigated, yet their underlying molecular mechanisms need further exploration. Independent invasions of high-altitude plateaus, subterranean burrows and marine environments by different mammals provide opportunities to conduct such analyses. Here, we focused on six genes in the hypoxia inducible factor (HIF) pathway and two non-shivering thermogenesis (NST)-related genes [PPAR co-activator 1 (PGC-1) and uncoupling protein 1 (UCP1)] in representative species of pikas and other mammals to understand whether these loci were targeted by natural selection during independent invasions to conditions characterized by hypoxia and temperature fluctuations by high-altitude, subterranean and marine mammals. Our analyses revealed pervasive positive selection signals in the HIF pathway genes of mammals occupying high-altitude, subterranean and aquatic ecosystems; however, the mechanisms underlying their independent adaptations to hypoxic environments varied by taxa, since different genes were positively selected in each taxon and expression levels of individual genes varied among species. Additionally, parallel amino acid substitutions were also detected in hypoxia-tolerant mammals, indicating that convergent evolution may play a role in their independent adaptations to hypoxic environments. However, divergent evolutionary histories of NST-related genes were noted, since significant evidence of positive selection was observed in PGC-1 and UCP1 in high-altitude species and subterranean rodents; however, UCP1 may have already lost its function in diving cetaceans, which may be related to the thick blubber layer of adipose and connective tissue in these mammals.}, } @article {pmid30327575, year = {2018}, author = {York, A}, title = {Silencing Staphylococcus aureus with probiotics.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {715}, doi = {10.1038/s41579-018-0111-3}, pmid = {30327575}, issn = {1740-1534}, } @article {pmid30327573, year = {2018}, author = {Svardal, H and Jasinska, AJ and Apetrei, C and Coppola, G and Huang, Y and Schmitt, CA and Jacquelin, B and Ramensky, V and Müller-Trutwin, M and Antonio, M and Weinstock, G and Grobler, JP and Dewar, K and Wilson, RK and Turner, TR and Warren, WC and Freimer, NB and Nordborg, M}, title = {Publisher Correction: Ancient hybridization and strong adaptation to viruses across African vervet monkey populations.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1617}, doi = {10.1038/s41588-018-0124-x}, pmid = {30327573}, issn = {1546-1718}, abstract = {In the version of this article published, in the Online Methods eight citations to supplementary material refer to the wrong supplementary items. See the correction notice for full details.}, } @article {pmid30327530, year = {2018}, author = {}, title = {Journal blacklists: show your working.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {308}, doi = {10.1038/d41586-018-07033-5}, pmid = {30327530}, issn = {1476-4687}, } @article {pmid30327529, year = {2018}, author = {Curry, A}, title = {The internet of animals that could help to save vanishing wildlife.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {322-326}, doi = {10.1038/d41586-018-07036-2}, pmid = {30327529}, issn = {1476-4687}, } @article {pmid30327528, year = {2018}, author = {Schiermeier, Q}, title = {Tsunami scientists clash with Indonesian government over rules on foreign research.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {317-318}, doi = {10.1038/d41586-018-07030-8}, pmid = {30327528}, issn = {1476-4687}, } @article {pmid30327527, year = {2018}, author = {Larson, HJ}, title = {The biggest pandemic risk? Viral misinformation.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {309}, doi = {10.1038/d41586-018-07034-4}, pmid = {30327527}, issn = {1476-4687}, } @article {pmid30327526, year = {2018}, author = {Castelvecchi, D}, title = {All systems go for second-ever mission to enter Mercury's orbit.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {320-321}, doi = {10.1038/d41586-018-06996-9}, pmid = {30327526}, issn = {1476-4687}, } @article {pmid30327525, year = {2018}, author = {Pietrzyński, G}, title = {Twenty-five years of using microlensing to study dark matter.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {349-350}, doi = {10.1038/d41586-018-07006-8}, pmid = {30327525}, issn = {1476-4687}, } @article {pmid30327524, year = {2018}, author = {Warren, M}, title = {Climate change is about to make your beer more expensive.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {319-320}, doi = {10.1038/d41586-018-07015-7}, pmid = {30327524}, issn = {1476-4687}, } @article {pmid30327523, year = {2018}, author = {Baker, C}, title = {Promises and pitfalls of imaging the brain.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {340-342}, doi = {10.1038/d41586-018-07043-3}, pmid = {30327523}, issn = {1476-4687}, } @article {pmid30327520, year = {2018}, author = {Gewin, V}, title = {Real-life stories of online harassment - and how scientists got through it.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {449-450}, doi = {10.1038/d41586-018-07046-0}, pmid = {30327520}, issn = {1476-4687}, } @article {pmid30327519, year = {2018}, author = {Shang, L and Crowley, M and Dando, M}, title = {Act now to close chemical-weapons loophole.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {344}, doi = {10.1038/d41586-018-07058-w}, pmid = {30327519}, issn = {1476-4687}, } @article {pmid30327518, year = {2018}, author = {Röer, JP}, title = {All scientists deserve a break from e-mail on holiday - not just professors.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {344}, doi = {10.1038/d41586-018-07060-2}, pmid = {30327518}, issn = {1476-4687}, mesh = {Communication ; *Electronic Mail ; *Holidays ; Research ; Work-Life Balance ; }, } @article {pmid30327517, year = {2018}, author = {}, title = {Mouse, annotated: an atlas maps cells' fates as an embryo develops.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {310-311}, doi = {10.1038/d41586-018-07016-6}, pmid = {30327517}, issn = {1476-4687}, } @article {pmid30327516, year = {2018}, author = {}, title = {Material zips itself back together thanks to the power of attraction.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {310}, doi = {10.1038/d41586-018-07010-y}, pmid = {30327516}, issn = {1476-4687}, } @article {pmid30327515, year = {2018}, author = {Callaway, E}, title = {Supercharged crime-scene DNA analysis sparks privacy concerns.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {315-316}, doi = {10.1038/d41586-018-06997-8}, pmid = {30327515}, issn = {1476-4687}, } @article {pmid30327514, year = {2018}, author = {Catanzaro, M}, title = {Argentina's scientists struggle amid slipping peso and rising inflation.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {316-317}, doi = {10.1038/d41586-018-07003-x}, pmid = {30327514}, issn = {1476-4687}, } @article {pmid30327513, year = {2018}, author = {}, title = {World's littlest light-sensing gyroscope fits on a grain of rice.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {311}, doi = {10.1038/d41586-018-06992-z}, pmid = {30327513}, issn = {1476-4687}, } @article {pmid30327512, year = {2018}, author = {}, title = {An ordinary human recognizes thousands of faces.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {311}, doi = {10.1038/d41586-018-06998-7}, pmid = {30327512}, issn = {1476-4687}, } @article {pmid30327511, year = {2018}, author = {Butler, D}, title = {French plant biologist cleared of misconduct in new inquiry.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {318-319}, doi = {10.1038/d41586-018-06966-1}, pmid = {30327511}, issn = {1476-4687}, } @article {pmid30327510, year = {2018}, author = {}, title = {Polar bears turn to whale meat as their hunting grounds melt.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {310}, doi = {10.1038/d41586-018-06989-8}, pmid = {30327510}, issn = {1476-4687}, } @article {pmid30327509, year = {2018}, author = {}, title = {Six thousand pet dogs help find mutation for one breed's striking blue eyes.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {310}, doi = {10.1038/d41586-018-06987-w}, pmid = {30327509}, issn = {1476-4687}, } @article {pmid30327508, year = {2018}, author = {}, title = {Spacecraft beware: huge spines of ice might guard a glimmering moon.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {311}, doi = {10.1038/d41586-018-06985-y}, pmid = {30327508}, issn = {1476-4687}, } @article {pmid30327497, year = {2018}, author = {Winters, IP and Murray, CW and Winslow, MM}, title = {Publisher Correction: Towards quantitative and multiplexed in vivo functional cancer genomics.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {801}, doi = {10.1038/s41576-018-0062-6}, pmid = {30327497}, issn = {1471-0064}, abstract = {The originally published article failed to acknowledge the equal first authorship contribution of I. P. Winters and C. W. Murray. The article has now been corrected online. The editors apologize for this error.}, } @article {pmid30327492, year = {2018}, author = {Howard, NC and Marin, ND and Ahmed, M and Rosa, BA and Martin, J and Bambouskova, M and Sergushichev, A and Loginicheva, E and Kurepina, N and Rangel-Moreno, J and Chen, L and Kreiswirth, BN and Klein, RS and Balada-Llasat, JM and Torrelles, JB and Amarasinghe, GK and Mitreva, M and Artyomov, MN and Hsu, FF and Mathema, B and Khader, SA}, title = {Publisher Correction: Mycobacterium tuberculosis carrying a rifampicin drug resistance mutation reprograms macrophage metabolism through cell wall lipid changes.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1327}, doi = {10.1038/s41564-018-0281-9}, pmid = {30327492}, issn = {2058-5276}, support = {R01 AI081803/AI/NIAID NIH HHS/United States ; R01 GM097435/GM/NIGMS NIH HHS/United States ; }, abstract = {In the version of this Letter originally published, in Fig. 2d, in the third graph, the label for the y axis was incorrect as 'TNF-α (pg ml-1)'; it should have read 'IL-1β (pg ml-1)'. This has now been corrected.}, } @article {pmid30327388, year = {2018}, author = {Gilbert, N}, title = {News Feature: Deadly deficiency at the heart of an environmental mystery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10532-10536}, pmid = {30327388}, issn = {1091-6490}, mesh = {Animals ; *Environment ; Paralysis/*etiology ; *Reproduction ; Thiamine Deficiency/*complications ; }, } @article {pmid30327349, year = {2018}, author = {Kodama, T and Yi, J and Newberg, JY and Tien, JC and Wu, H and Finegold, MJ and Kodama, M and Wei, Z and Tamura, T and Takehara, T and Johnson, RL and Jenkins, NA and Copeland, NG}, title = {Molecular profiling of nonalcoholic fatty liver disease-associated hepatocellular carcinoma using SB transposon mutagenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10417-E10426}, pmid = {30327349}, issn = {1091-6490}, mesh = {Animals ; Apoptosis/genetics ; Carcinogenesis/genetics/pathology ; Carcinoma, Hepatocellular/*genetics/*pathology ; Cell Transformation, Neoplastic/genetics/pathology ; DNA Transposable Elements/*genetics ; Diet, High-Fat/adverse effects ; Liver/pathology ; Liver Neoplasms/*genetics/*pathology ; Mice ; Mutagenesis/genetics ; Non-alcoholic Fatty Liver Disease/*genetics/*pathology ; Oncogenes/genetics ; Signal Transduction/genetics ; Up-Regulation/genetics ; }, abstract = {Nonalcoholic fatty liver disease (NAFLD) is the fastest rising cause of hepatocellular carcinoma (HCC) in Western countries; however, the molecular mechanisms that cause NAFLD-HCC remain elusive. To identify molecular drivers of NAFLD-HCC, we performed Sleeping Beauty (SB) transposon mutagenesis screens in liver-specific Pten knockout and in high-fat diet-fed mice, which are murine models of NAFLD-HCC. SB mutagenesis accelerated liver tumor formation in both models and identified 588 and 376 candidate cancer genes (CCGs), respectively; 257 CCGs were common to both screens and were enriched in signaling pathways known to be important for human HCC. Comparison of these CCGs with those identified in a previous SB screen of hepatitis B virus-induced HCC identified a core set of 141 CCGs that were mutated in all screens. Forty-one CCGs appeared specific for NAFLD-HCC, including Sav1, a component of the Hippo signaling pathway and the most frequently mutated gene identified in both NAFLD-HCC screens. Liver-specific deletion of Sav1 was found to promote hepatic lipid accumulation, apoptosis, and fibrogenesis, leading to the acceleration of hepatocarcinogenesis in liver-specific Pten mutant mice. Sav1/Pten double-mutant livers also showed a striking up-regulation of markers of liver progenitor cells (LPCs), along with synergistic activation of Yap, which is a major downstream effector of Hippo signaling. Lastly, Yap activation, in combination with Pten inactivation, was found to accelerate cell growth and sphere formation of LPCs in vitro and induce their malignant transformation in allografts. Our forward genetic screens in mice have thus identified pathways and genes driving the development of NAFLD-HCC.}, } @article {pmid30327348, year = {2018}, author = {Zhao, H and Zhou, L and Li, L and Coon V, J and Chatterton, RT and Brooks, DC and Jiang, E and Liu, L and Xu, X and Dong, Z and DeMayo, FJ and Stulberg, JJ and Tourtellotte, WG and Bulun, SE}, title = {Shift from androgen to estrogen action causes abdominal muscle fibrosis, atrophy, and inguinal hernia in a transgenic male mouse model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10427-E10436}, pmid = {30327348}, issn = {1091-6490}, mesh = {Abdominal Muscles/*pathology ; Animals ; Aromatase/metabolism ; Estradiol/*metabolism ; Estrogen Receptor alpha ; Fibrosis/*pathology ; Gene Expression Regulation, Enzymologic ; Hernia, Inguinal/*pathology ; Male ; Mice ; Mice, Transgenic ; Models, Animal ; Muscle, Skeletal/pathology ; Muscular Atrophy/*metabolism/pathology ; Receptors, Androgen ; Testosterone/*metabolism ; }, abstract = {Inguinal hernia develops primarily in elderly men, and more than one in four men will undergo inguinal hernia repair during their lifetime. However, the underlying mechanisms behind hernia formation remain unknown. It is known that testosterone and estradiol can regulate skeletal muscle mass. We herein demonstrate that the conversion of testosterone to estradiol by the aromatase enzyme in lower abdominal muscle (LAM) tissue causes intense fibrosis, leading to muscle atrophy and inguinal hernia; an aromatase inhibitor entirely prevents this phenotype. LAM tissue is uniquely sensitive to estradiol because it expresses very high levels of estrogen receptor-α. Estradiol acts via estrogen receptor-α in LAM fibroblasts to activate pathways for proliferation and fibrosis that replaces atrophied myocytes, resulting in hernia formation. This is accompanied by decreased serum testosterone and decreased expression of the androgen receptor target genes in LAM tissue. These findings provide a mechanism for LAM tissue fibrosis and atrophy and suggest potential roles of future nonsurgical and preventive approaches in a subset of elderly men with a predisposition for hernia development.}, } @article {pmid30327347, year = {2018}, author = {Li, M and Reimers, JR and Dobson, JF and Gould, T}, title = {Faraday cage screening reveals intrinsic aspects of the van der Waals attraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10295-E10302}, pmid = {30327347}, issn = {1091-6490}, abstract = {General properties of the recently observed screening of the van der Waals (vdW) attraction between a silica substrate and silica tip by insertion of graphene are predicted using basic theory and first-principles calculations. Results are then focused on possible practical applications, as well as an understanding of the nature of vdW attraction, considering recent discoveries showing it competing against covalent and ionic bonding. The traditional view of the vdW attraction as arising from pairwise-additive London dispersion forces is considered using Grimme's "D3" method, comparing results to those from Tkatchenko's more general many-body dispersion (MBD) approach, all interpreted in terms of Dobson's general dispersion framework. Encompassing the experimental results, MBD screening of the vdW force between two silica bilayers is shown to scale up to medium separations as 1.25 de/d, where d is the bilayer separation and de is its equilibrium value, depicting antiscreening approaching and inside de Means of unifying this correlation effect with those included in modern density functionals are urgently required.}, } @article {pmid30327346, year = {2018}, author = {Cao, H and Yadav, RK and Aurnou, JM}, title = {Geomagnetic polar minima do not arise from steady meridional circulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11186-11191}, pmid = {30327346}, issn = {1091-6490}, abstract = {Observations of the Earth's magnetic field have revealed locally pronounced field minima near each pole at the core-mantle boundary (CMB). The existence of the polar magnetic minima has long been attributed to the supposed large-scale overturning circulation of molten metal in the outer core: Fluid upwells within the inner core tangent cylinder toward the poles and then diverges toward lower latitudes when it reaches the CMB, where Coriolis effects sweep the fluid into anticyclonic vortical flows. The diverging near-surface meridional circulation is believed to advectively draw magnetic flux away from the poles, resulting in the low intensity or even reversed polar magnetic fields. However, the interconnections between polar magnetic minima and meridional circulations have not to date been ascertained quantitatively. Here, we quantify the magnetic effects of steady, axisymmetric meridional circulation via numerically solving the axisymmetric magnetohydrodynamic equations for Earth's outer core under the magnetostrophic approximation. Extrapolated to core conditions, our results show that the change in polar magnetic field resulting from steady, large-scale meridional circulations in Earth's outer core is less than [Formula: see text] of the background field, significantly smaller than the [Formula: see text] polar magnetic minima observed at the CMB. This suggests that the geomagnetic polar minima cannot be produced solely by axisymmetric, steady meridional circulations and must depend upon additional tangent cylinder dynamics, likely including nonaxisymmetric, time-varying processes.}, } @article {pmid30327345, year = {2018}, author = {Dyballa, L and Hoseini, MS and Dadarlat, MC and Zucker, SW and Stryker, MP}, title = {Flow stimuli reveal ecologically appropriate responses in mouse visual cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11304-11309}, pmid = {30327345}, issn = {1091-6490}, support = {R01 EY002874/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Microelectrodes ; Neurons/*physiology ; Orientation/physiology ; Photic Stimulation/methods ; Space Perception/physiology ; Visual Cortex/*physiology ; }, abstract = {Assessments of the mouse visual system based on spatial-frequency analysis imply that its visual capacity is low, with few neurons responding to spatial frequencies greater than 0.5 cycles per degree. However, visually mediated behaviors, such as prey capture, suggest that the mouse visual system is more precise. We introduce a stimulus class-visual flow patterns-that is more like what the mouse would encounter in the natural world than are sine-wave gratings but is more tractable for analysis than are natural images. We used 128-site silicon microelectrodes to measure the simultaneous responses of single neurons in the primary visual cortex (V1) of alert mice. While holding temporal-frequency content fixed, we explored a class of drifting patterns of black or white dots that have energy only at higher spatial frequencies. These flow stimuli evoke strong visually mediated responses well beyond those predicted by spatial-frequency analysis. Flow responses predominate in higher spatial-frequency ranges (0.15-1.6 cycles per degree), many are orientation or direction selective, and flow responses of many neurons depend strongly on sign of contrast. Many cells exhibit distributed responses across our stimulus ensemble. Together, these results challenge conventional linear approaches to visual processing and expand our understanding of the mouse's visual capacity to behaviorally relevant ranges.}, } @article {pmid30327344, year = {2018}, author = {Zhang, Y and Wen, WH and Pu, JY and Tang, MC and Zhang, L and Peng, C and Xu, Y and Tang, GL}, title = {Extracellularly oxidative activation and inactivation of matured prodrug for cryptic self-resistance in naphthyridinomycin biosynthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11232-11237}, pmid = {30327344}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/*metabolism ; Naphthyridines/metabolism ; Oxidation-Reduction ; Oxidoreductases/metabolism ; Peptide Synthases/metabolism ; Prodrugs/*metabolism ; Streptomyces/*metabolism ; }, abstract = {Understanding how antibiotic-producing bacteria deal with highly reactive chemicals will ultimately guide therapeutic strategies to combat the increasing clinical resistance crisis. Here, we uncovered a distinctive self-defense strategy featured by a secreted oxidoreductase NapU to perform extracellularly oxidative activation and conditionally overoxidative inactivation of a matured prodrug in naphthyridinomycin (NDM) biosynthesis from Streptomyces lusitanus NRRL 8034. It was suggested that formation of NDM first involves a nonribosomal peptide synthetase assembly line to generate a prodrug. After exclusion and prodrug maturation, we identified a pharmacophore-inactivated intermediate, which required reactivation by NapU via oxidative C-H bond functionalization extracellularly to afford NDM. Beyond that, NapU could further oxidatively inactivate the NDM pharmacophore to avoid self-cytotoxicity if they coexist longer than necessary. This discovery represents an amalgamation of sophisticatedly temporal and spatial shielding mode conferring self-resistance in antibiotic biosynthesis from Gram-positive bacteria.}, } @article {pmid30327343, year = {2018}, author = {Cho, S and Muthukumar, AK and Stork, T and Coutinho-Budd, JC and Freeman, MR}, title = {Focal adhesion molecules regulate astrocyte morphology and glutamate transporters to suppress seizure-like behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11316-11321}, pmid = {30327343}, issn = {1091-6490}, support = {R01 NS053538/NS/NINDS NIH HHS/United States ; S10 RR027897/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/*metabolism ; Biological Transport/physiology ; Drosophila/metabolism ; Excitatory Amino Acid Transporter 1/metabolism ; Focal Adhesions/*metabolism ; Glutamates/*metabolism ; Neurons/metabolism ; Seizures/metabolism ; }, abstract = {Astrocytes are important regulators of neural circuit function and behavior in the healthy and diseased nervous system. We screened for molecules in Drosophila astrocytes that modulate neuronal hyperexcitability and identified multiple components of focal adhesion complexes (FAs). Depletion of astrocytic Tensin, β-integrin, Talin, focal adhesion kinase (FAK), or matrix metalloproteinase 1 (Mmp1), resulted in enhanced behavioral recovery from genetic or pharmacologically induced seizure. Overexpression of Mmp1, predicted to activate FA signaling, led to a reciprocal enhancement of seizure severity. Blockade of FA-signaling molecules in astrocytes at basal levels of CNS excitability resulted in reduced astrocytic coverage of the synaptic neuropil and expression of the excitatory amino acid transporter EAAT1. However, induction of hyperexcitability after depletion of FA-signaling components resulted in enhanced astrocyte coverage and an approximately twofold increase in EAAT1 levels. Our work identifies FA-signaling molecules as important regulators of astrocyte outgrowth and EAAT1 expression under normal physiological conditions. Paradoxically, in the context of hyperexcitability, this pathway negatively regulates astrocytic process outgrowth and EAAT1 expression, and their blockade leading to enhanced recovery from seizure.}, } @article {pmid30327342, year = {2018}, author = {Zuo, W and Jiang, S and Guo, Z and Feldman, MW and Tuljapurkar, S}, title = {Advancing front of old-age human survival.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11209-11214}, pmid = {30327342}, issn = {1091-6490}, mesh = {Aged ; Cause of Death ; Death ; Female ; Forecasting ; Global Health/statistics & numerical data ; Humans ; Life Expectancy/*trends ; Life Tables ; Male ; Mortality/*trends ; }, abstract = {Old-age mortality decline has driven recent increases in lifespans, but there is no agreement about trends in the age pattern of old-age deaths. Some argue that old-age deaths should become compressed at advanced ages, others argue that old-age deaths should become more dispersed with age, and yet others argue that old-age deaths are consistent with little change in dispersion. However, direct analysis of old-age deaths presents unusual challenges: Death rates at the oldest ages are always noisy, published life tables must assume an asymptotic age pattern of deaths, and the definition of "old-age" changes as lives lengthen. Here we use robust percentile-based methods to overcome some of these challenges and show, for five decades in 20 developed countries, that old-age survival follows an advancing front, like a traveling wave. The front lies between the 25th and 90th percentiles of old-age deaths, advancing with nearly constant long-term shape but annual fluctuations in speed. The existence of this front leads to several predictions that we verify, e.g., that advances in life expectancy at age 65 y are highly correlated with the advance of the 25th percentile, but not with distances between higher percentiles. Our unexpected result has implications for biological hypotheses about human aging and for future mortality change.}, } @article {pmid30327341, year = {2018}, author = {Mohamad, MA and Sapsis, TP}, title = {Sequential sampling strategy for extreme event statistics in nonlinear dynamical systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11138-11143}, pmid = {30327341}, issn = {1091-6490}, abstract = {We develop a method for the evaluation of extreme event statistics associated with nonlinear dynamical systems from a small number of samples. From an initial dataset of design points, we formulate a sequential strategy that provides the "next-best" data point (set of parameters) that when evaluated results in improved estimates of the probability density function (pdf) for a scalar quantity of interest. The approach uses Gaussian process regression to perform Bayesian inference on the parameter-to-observation map describing the quantity of interest. We then approximate the desired pdf along with uncertainty bounds using the posterior distribution of the inferred map. The next-best design point is sequentially determined through an optimization procedure that selects the point in parameter space that maximally reduces uncertainty between the estimated bounds of the pdf prediction. Since the optimization process uses only information from the inferred map, it has minimal computational cost. Moreover, the special form of the metric emphasizes the tails of the pdf. The method is practical for systems where the dimensionality of the parameter space is of moderate size and for problems where each sample is very expensive to obtain. We apply the method to estimate the extreme event statistics for a very high-dimensional system with millions of degrees of freedom: an offshore platform subjected to 3D irregular waves. It is demonstrated that the developed approach can accurately determine the extreme event statistics using a limited number of samples.}, } @article {pmid30327165, year = {2019}, author = {Molnar, A}, title = {Antimicrobial Resistance Awareness and Games.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {1-3}, doi = {10.1016/j.tim.2018.09.007}, pmid = {30327165}, issn = {1878-4380}, abstract = {Antibiotic resistance is an increasingly global problem that requires different approaches to be undertaken. This article argues that games could be used to complement existing antibiotic-resistance awareness campaigns as they have several characteristics that could help people engage with information.}, } @article {pmid30327160, year = {2019}, author = {Schurer, JM and Dang-Xuan, S and Farag, M}, title = {Just Enough Cooks in the Kitchen: Key Ingredients for International Collaboration.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {1-4}, doi = {10.1016/j.pt.2018.09.005}, pmid = {30327160}, issn = {1471-5007}, abstract = {Research approaches that cross disciplinary silos, industry sectors, and political borders are now increasingly prioritized for tackling issues of global concern. Nevertheless, team science can be challenging. The goal of this article is to help researchers proactively consider factors influencing conflicts and successes with an emphasis on the health sciences.}, } @article {pmid30326974, year = {2018}, author = {De Mel, S and Jayarajah, U and Seneviratne, SA}, title = {Medical undergraduates' perceptions on the end of course assessment in Surgery in a developing country in South Asia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {731}, pmid = {30326974}, issn = {1756-0500}, mesh = {Adult ; Education, Medical, Undergraduate/methods/*standards ; Educational Measurement/methods/*standards ; Feedback ; Female ; General Surgery/*education ; Humans ; Male ; Sri Lanka ; *Students, Medical ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: This study reports findings from a feedback assessment conducted among final year medical undergraduates on the end of course assessment in Surgery. A self-administered questionnaire was used among 201 final year medical undergraduates of the Faculty of Medicine Colombo to collect students' perceptions on clinical assessment (i.e. long and short cases), performance of examiners during clinical assessments and student perceptions on different types of undergraduate assessments in Surgery.

RESULTS: Approximately 90% of undergraduates perceived that both long and short case assessments were fair in assessing their knowledge and clinical skills. On the overall assessment in Surgery, approximately 90% agreed that tasks reflected those taught, assessment covered a wide area of knowledge and skills in Surgery and time given for assessment was adequate. Most felt long case to be the best method in assessing whether one is a safe doctor with good communication skills and ability to apply knowledge practically. Thus, a majority of students were satisfied with the current assessment system and most perceived the clinical component to be superior to all other components in assessing whether a student is suitable to become a good and a safe doctor.}, } @article {pmid30326972, year = {2018}, author = {Michailidis, L and Bergin, SM and Haines, TP and Williams, CM}, title = {Healing rates in diabetes-related foot ulcers using low frequency ultrasonic debridement versus non-surgical sharps debridement: a randomised controlled trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {732}, pmid = {30326972}, issn = {1756-0500}, mesh = {Adult ; Debridement/*methods ; Diabetic Foot/*therapy ; Humans ; *Outcome Assessment (Health Care) ; Ultrasonic Therapy/*methods ; }, abstract = {OBJECTIVE: Current clinical practice varies around debridement techniques used to promote healing of diabetes-related foot ulcers. This randomised controlled study will compare healing rates for diabetes-related foot ulcers treated with low frequency ultrasonic debridement versus non-surgical sharps debridement. Individuals with diabetes-related foot ulcers being managed by podiatry at a metropolitan hospital were screened against study criteria. Eligible participants were randomly allocated to either the non-surgical sharps debridement group or the low frequency ultrasonic debridement group and received weekly treatment for 6 months. Participants also completed a quality of life measure and visual analogue pain scale.

RESULTS: This trial was ended early due to recruitment issues. Ten participants with 14 ulcers participated. Results were analysed using a survival analysis approach. Ulcers treated with non-surgical sharps debridement healed more quickly (61.6 days ± 24.4) compared with low frequency ultrasonic debridement (117.6 days ± 40.3). In both groups, quality of life was observed to improve as ulcers healed and pain levels reduced as ulcers improved. Observations from this study found faster healing using non-surgical sharps debridement. However, these results are unable to be generalised due to the small sample size. Further research is recommended. Trial registration Australian New Zealand Clinical Trial Registry: ACTRN12612000490875.}, } @article {pmid30326961, year = {2018}, author = {Bazezew, MM and Yallew, WW and Belew, AK}, title = {Knowledge and practice of iodized salt utilization among reproductive women in Addis Ababa City.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {734}, pmid = {30326961}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; *Diet ; Ethiopia ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; *Iodine ; Middle Aged ; *Sodium Chloride, Dietary ; Young Adult ; }, abstract = {OBJECTIVE: The objective of this study was to assess knowledge and practice of iodized salt utilization among reproductive women in Addis Ababa city. A cross-sectional study was carried out on 549 households. A sample district was designated by using the simple random sampling techniques. Data were collected by a face-to-face interview and household salt was tested to check whether its practice was good. p < 0.2 in the bivariate logistic regression was entered into the multivariable logistic regression, and p < 0.05 was considered as significantly associated.

RESULTS: Mothers who had good knowledge and practice of iodized salt were 78% (95% CI 74.9, 81.2) and 76.3% (95% CI 72.7, 79.8), respectively. Monthly household income (AOR = 2.97; 95% CI 1.20, 7.37) was associated with knowledge of iodized salt of respondents. Similarly, educational status (AOR = 2.45; 95% CL 2.10, 6.43) of respondents was significantly associated with the practice of iodized salt. This study indicated that increasing the level of knowledge and practice of iodized salt was good. Monthly household income and educational status were associated with knowledge and practices of iodized salt of respondents. Hence, improving mothers' education is a highly recommended strategy for addressing public health problems of iodine deficiency.}, } @article {pmid30326957, year = {2018}, author = {Kondkar, AA and Sultan, T and Almobarak, FA and Kalantan, H and Abu-Amero, KK and Al-Obeidan, SA}, title = {Plexin domain containing 2 (PLXDC2) gene polymorphism rs7081455 may not influence POAG risk in a Saudi cohort.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {733}, pmid = {30326957}, issn = {1756-0500}, mesh = {Aged ; Case-Control Studies ; Female ; Glaucoma, Open-Angle/*genetics/*physiopathology ; Humans ; Male ; Middle Aged ; Polymorphism, Genetic ; Receptors, Cell Surface/*genetics ; Saudi Arabia ; }, abstract = {OBJECTIVE: Plexin domain containing 2 (PLXDC2), a cell surface transmembrane protein receptor for pigment epithelium derived factor, is expressed in many tissues including the eye. Polymorphism rs7081455 flanking PLXDC2 has been associated with primary open angle glaucoma (POAG) and its clinical phenotypes and may have a role in POAG. Rs7081455 was genotyped in POAG cases (n = 188) and non-glaucomatous controls (n = 164) of Saudi origin using Taq-Man® to determine any association of this variant with POAG and its endophenotypes.

RESULTS: The risk variant, 'G' allele, frequency was 0.56 and 0.52 in controls and POAG cases, respectively (p = 0.197) with was no significant deviation from Hardy-Weinberg equilibrium. Genotype analysis between cases and controls revealed no significant distribution under additive (p = 0.482), dominant (p = 0.590) and recessive models (p = 0.228). In addition, glaucoma specific phenotypic traits such as intraocular pressure (IOP) and cup/disc ratio; and number of anti-glaucoma medications, used to assess severity of the disease, were also statistically non-significant. Furthermore, regression analysis showed no significant effect of age, sex and genotype on disease outcome. Rs7081455 was not associated with POAG or its clinical phenotypes such as IOP and cup/disc ratio and hence may not be a significant risk factor for POAG patients of Saudi origin.}, } @article {pmid30326954, year = {2018}, author = {Korpela, K and Salonen, A and Vepsäläinen, O and Suomalainen, M and Kolmeder, C and Varjosalo, M and Miettinen, S and Kukkonen, K and Savilahti, E and Kuitunen, M and de Vos, WM}, title = {Probiotic supplementation restores normal microbiota composition and function in antibiotic-treated and in caesarean-born infants.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {182}, pmid = {30326954}, issn = {2049-2618}, abstract = {BACKGROUND: Infants born by caesarean section or receiving antibiotics are at increased risk of developing metabolic, inflammatory and immunological diseases, potentially due to disruption of normal gut microbiota at a critical developmental time window. We investigated whether probiotic supplementation could ameliorate the effects of antibiotic use or caesarean birth on infant microbiota in a double blind, placebo-controlled randomized clinical trial. Mothers were given a multispecies probiotic, consisting of Bifidobacterium breve Bb99 (Bp99 2 × 108 cfu) Propionibacterium freundenreichii subsp. shermanii JS (2 × 109cfu), Lactobacillus rhamnosus Lc705 (5 × 109 cfu) and Lactobacillus rhamnosus GG (5 × 109 cfu) (N = 168 breastfed and 31 formula-fed), or placebo supplement (N = 201 breastfed and 22 formula-fed) during pregnancy, and the infants were given the same supplement. Faecal samples of the infants were collected at 3 months and analyzed using taxonomic, metagenomic and metaproteomic approaches.

RESULTS: The probiotic supplement had a strong overall impact on the microbiota composition, but the effect depended on the infant's diet. Only breastfed infants showed the expected increase in bifidobacteria and reduction in Proteobacteria and Clostridia. In the placebo group, both birth mode and antibiotic use were significantly associated with altered microbiota composition and function, particularly reduced Bifidobacterium abundance. In the probiotic group, the effects of antibiotics and birth mode were either completely eliminated or reduced.

CONCLUSIONS: The results indicate that it is possible to correct undesired changes in microbiota composition and function caused by antibiotic treatments or caesarean birth by supplementing infants with a probiotic mixture together with at least partial breastfeeding.

TRIAL REGISTRATION: clinicaltrials.gov NCT00298337 . Registered March 2, 2006.}, } @article {pmid30326942, year = {2018}, author = {de Santana, NM and Dos Santos Figueiredo, FW and de Melo Lucena, DM and Soares, FM and Adami, F and de Carvalho Pádua Cardoso, L and Correa, JA}, title = {The burden of stroke in Brazil in 2016: an analysis of the Global Burden of Disease study findings.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {735}, pmid = {30326942}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Brain Ischemia/*epidemiology/mortality ; Brazil/epidemiology ; *Cost of Illness ; Disabled Persons/*statistics & numerical data ; Female ; Global Burden of Disease/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Quality-Adjusted Life Years ; Sex Factors ; Stroke/*epidemiology/mortality ; Young Adult ; }, abstract = {OBJECTIVE: To analyze the epidemiological stroke data of Brazil according to the Global Burden of Disease (GBD) study in 2016 and secondary data from the GBD database.

RESULTS: The highest percentage of deaths due to stroke in general occurred in individuals aged 70 years or over (60.2%; 95% confidence interval [CI] 59.9-60.5%) followed by that in men (52.9%; 95% CI 52.6-53.2%). Ischemic stroke was the most common type, accounting for 61.8% (95% CI 61.5-62.1%) of deaths due to stroke in 2016. Most of the epidemiological indicators (incidence, prevalence, mortality-to-incidence ratio, mortality, disability-adjusted life years, years lost due to disability, and years of life lost) of stroke in general or either type of stroke were higher in men and those aged 70 years or over. Stroke data in Brazil are a major concern and represent a real health challenge for the coming decades. Men and individuals aged 70 years or older appear to represent the groups with the highest epidemiological parameters and risk for the various stroke outcomes. However, this does not mean the female data are irrelevant, which, although representing a lower risk than the male data, also raise the need for policies aimed at prevention and improvement in the treatment of stroke and its sequelae.}, } @article {pmid30326850, year = {2018}, author = {Taïbi, K and Del Campo, AD and Vilagrosa, A and Bellés, JM and López-Gresa, MP and López-Nicolás, JM and Mulet, JM}, title = {Distinctive physiological and molecular responses to cold stress among cold-tolerant and cold-sensitive Pinus halepensis seed sources.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {236}, pmid = {30326850}, issn = {1471-2229}, support = {PAID-05-11//Universitat Politècnica de València/ ; PAID-05-11//Universitat Politècnica de València/ ; AGL2014-57431-P//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; BIO2016-77776-P//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; CGL2015-69773-C2-2-P MINECO/FEDER//Ministerio de Economía y Competitividad/ ; DESESTRES//Generalitat Valenciana/ ; AICO/2018/300//Generalitat Valenciana/ ; }, mesh = {Climate Change ; Cold Temperature ; Phenotype ; Photosynthesis/physiology ; Pinus/genetics/*physiology ; Plant Transpiration/physiology ; Seedlings/genetics/physiology ; Seeds/genetics/physiology ; *Stress, Physiological ; Water/physiology ; }, abstract = {BACKGROUND: Forest species ranges are confined by environmental limitations such as cold stress. The natural range shifts of pine forests due to climate change and proactive-assisted population migration may each be constrained by the ability of pine species to tolerate low temperatures, especially in northern latitudes or in high altitudes. The aim of this study is to characterize the response of cold-tolerant versus cold-sensitive Pinus halepensis (P. halepensis) seedlings at the physiological and the molecular level under controlled cold conditions to identify distinctive features which allow us to explain the phenotypic difference. With this objective gas-exchange and water potential was determined and the photosynthetic pigments, soluble sugars, glutathione and free amino acids content were measured in seedlings of different provenances under control and cold stress conditions.

RESULTS: Glucose and fructose content can be highlighted as a potential distinctive trait for cold-tolerant P. halepensis seedlings. At the amino acid level, there was a significant increase and accumulation of glutathione, proline, glutamic acid, histidine, arginine and tryptophan along with a significant decrease of glycine.

CONCLUSION: Our results established that the main difference between cold-tolerant and cold-sensitive seedlings of P. halepensis is the ability to accumulate the antioxidant glutathione and osmolytes such as glucose and fructose, proline and arginine.}, } @article {pmid30326849, year = {2018}, author = {Aprile, A and Sabella, E and Vergine, M and Genga, A and Siciliano, M and Nutricati, E and Rampino, P and De Pascali, M and Luvisi, A and Miceli, A and Negro, C and De Bellis, L}, title = {Activation of a gene network in durum wheat roots exposed to cadmium.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {238}, pmid = {30326849}, issn = {1471-2229}, support = {PON01_01145/1-ISCOCEM//MIUR/ ; 2I19HY5//Apulia Region/ ; }, mesh = {Azetidinecarboxylic Acid/analogs & derivatives/metabolism ; Biological Transport ; Biomass ; Cadmium/metabolism/*toxicity ; Edible Grain ; Gene Expression Regulation, Plant/*drug effects ; Gene Regulatory Networks/*drug effects ; Hydroponics ; Methionine/metabolism ; Plant Roots/drug effects/genetics/physiology ; Plant Shoots/drug effects/genetics/physiology ; Triticum/drug effects/*genetics/physiology ; }, abstract = {BACKGROUND: Among cereals, durum wheat (Triticum turgidum L. subsp. durum) accumulates cadmium (Cd) at higher concentration if grown in Cd-polluted soils. Since cadmium accumulation is a risk for human health, the international trade organizations have limited the acceptable concentration of Cd in edible crops. Therefore, durum wheat cultivars accumulating low cadmium in grains should be preferred by farmers and consumers. To identify the response of durum wheat to the presence of Cd, the transcriptomes of roots and shoots of Creso and Svevo cultivars were sequenced after a 50-day exposure to 0.5 μM Cd in hydroponic solution.

RESULTS: No phytotoxic effects or biomass reduction was observed in Creso and Svevo plants at this Cd concentration. Despite this null effect, cadmium was accumulated in root tissues, in shoots and in grains suggesting a good cadmium translocation rate among tissues. The mRNA sequencing revealed a general transcriptome rearrangement after Cd treatment and more than 7000 genes were found differentially expressed in root and shoot tissues. Among these, the up-regulated genes in roots showed a clear correlation with cadmium uptake and detoxification. In particular, about three hundred genes were commonly up-regulated in Creso and Svevo roots suggesting a well defined molecular strategy characterized by the transcriptomic activation of several transcription factors mainly belonging to bHLH and WRKY families. bHLHs are probably the activators of the strong up-regulation of three NAS genes, responsible for the synthesis of the phytosiderophore nicotianamine (NA). Moreover, we found the overall up-regulation of the methionine salvage pathway that is tightly connected with NA synthesis and supply the S-adenosyl methionine necessary for NA biosynthesis. Finally, several vacuolar NA chelating heavy metal transporters were vigorously activated.

CONCLUSIONS: In conclusion, the exposure of durum wheat to cadmium activates in roots a complex gene network involved in cadmium translocation and detoxification from heavy metals. These findings are confident with a role of nicotianamine and methionine salvage pathway in the accumulation of cadmium in durum wheat.}, } @article {pmid30326846, year = {2018}, author = {Kang, Y and Nam, SH and Park, KS and Kim, Y and Kim, JW and Lee, E and Ko, JM and Lee, KA and Park, I}, title = {DeviCNV: detection and visualization of exon-level copy number variants in targeted next-generation sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {381}, pmid = {30326846}, issn = {1471-2105}, support = {A120030//Ministry of Health and Welfare/ ; NRF-2017R1E1A1A03070512//Ministry of Education (KR)/ ; }, mesh = {DNA Copy Number Variations/*genetics ; Exons/*genetics ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; }, abstract = {BACKGROUND: Targeted next-generation sequencing (NGS) is increasingly being adopted in clinical laboratories for genomic diagnostic tests.

RESULTS: We developed a new computational method, DeviCNV, intended for the detection of exon-level copy number variants (CNVs) in targeted NGS data. DeviCNV builds linear regression models with bootstrapping for every probe to capture the relationship between read depth of an individual probe and the median of read depth values of all probes in the sample. From the regression models, it estimates the read depth ratio of the observed and predicted read depth with confidence interval for each probe which is applied to a circular binary segmentation (CBS) algorithm to obtain CNV candidates. Then, it assigns confidence scores to those candidates based on the reliability and strength of the CNV signals inferred from the read depth ratios of the probes within them. Finally, it also provides gene-centric plots with confidence levels of CNV candidates for visual inspection. We applied DeviCNV to targeted NGS data generated for newborn screening and demonstrated its ability to detect novel pathogenic CNVs from clinical samples.

CONCLUSIONS: We propose a new pragmatic method for detecting CNVs in targeted NGS data with an intuitive visualization and a systematic method to assign confidence scores for candidate CNVs. Since DeviCNV was developed for use in clinical diagnosis, sensitivity is increased by the detection of exon-level CNVs.}, } @article {pmid30326845, year = {2018}, author = {Richter, A and Hölscher, T and Pausch, P and Sehrt, T and Brockhaus, F and Bange, G and Kovács, ÁT}, title = {Hampered motility promotes the evolution of wrinkly phenotype in Bacillus subtilis.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {155}, pmid = {30326845}, issn = {1471-2148}, mesh = {Bacillus subtilis/cytology/genetics/*physiology ; Bacterial Proteins/genetics ; *Biological Evolution ; DNA, Bacterial/genetics ; Gene Expression Regulation, Bacterial ; Movement ; Mutation/genetics ; Mutation Rate ; Operator Regions, Genetic/genetics ; Operon ; Phenotype ; Selection, Genetic ; }, abstract = {BACKGROUND: Selection for a certain trait in microbes depends on the genetic background of the strain and the selection pressure of the environmental conditions acting on the cells. In contrast to the sessile state in the biofilm, various bacterial cells employ flagellum-dependent motility under planktonic conditions suggesting that the two phenotypes are mutually exclusive. However, flagellum dependent motility facilitates the prompt establishment of floating biofilms on the air-medium interface, called pellicles. Previously, pellicles of B. subtilis were shown to be preferably established by motile cells, causing a reduced fitness of non-motile derivatives in the presence of the wild type strain.

RESULTS: Here, we show that lack of active flagella promotes the evolution of matrix overproducers that can be distinguished by the characteristic wrinkled colony morphotype. The wrinkly phenotype is associated with amino acid substitutions in the master repressor of biofilm-related genes, SinR. By analyzing one of the mutations, we show that it alters the tetramerization and DNA binding properties of SinR, allowing an increased expression of the operon responsible for exopolysaccharide production. Finally, we demonstrate that the wrinkly phenotype is advantageous when cells lack flagella, but not in the wild type background.

CONCLUSIONS: Our experiments suggest that loss of function phenotypes could expose rapid evolutionary adaptation in bacterial biofilms that is otherwise not evident in the wild type strains.}, } @article {pmid30326842, year = {2018}, author = {Zoledowska, S and Motyka-Pomagruk, A and Sledz, W and Mengoni, A and Lojkowska, E}, title = {High genomic variability in the plant pathogenic bacterium Pectobacterium parmentieri deciphered from de novo assembled complete genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {751}, pmid = {30326842}, issn = {1471-2164}, support = {2014/14/M/NZ8/00501//Narodowe Centrum Nauki/ ; }, mesh = {Bacteriophages/physiology ; *Genetic Variation ; Genome, Bacterial/*genetics ; Genomics ; Molecular Sequence Annotation ; Pectobacterium/*genetics/virology ; Phenotype ; Plants/*microbiology ; }, abstract = {BACKGROUND: Pectobacterium parmentieri is a newly established species within the plant pathogenic family Pectobacteriaceae. Bacteria belonging to this species are causative agents of diseases in economically important crops (e.g. potato) in a wide range of different environmental conditions, encountered in Europe, North America, Africa, and New Zealand. Severe disease symptoms result from the activity of P. parmentieri virulence factors, such as plant cell wall degrading enzymes. Interestingly, we observe significant phenotypic differences among P. parmentieri isolates regarding virulence factors production and the abilities to macerate plants. To establish the possible genomic basis of these differences, we sequenced 12 genomes of P. parmentieri strains (10 isolated in Poland, 2 in Belgium) with the combined use of Illumina and PacBio approaches. De novo genome assembly was performed with the use of SPAdes software, while annotation was conducted by NCBI Prokaryotic Genome Annotation Pipeline.

RESULTS: The pan-genome study was performed on 15 genomes (12 de novo assembled and three reference strains: P. parmentieri CFBP 8475T, P. parmentieri SCC3193, P. parmentieri WPP163). The pan-genome includes 3706 core genes, a high number of accessory (1468) genes, and numerous unique (1847) genes. We identified the presence of well-known genes encoding virulence factors in the core genome fraction, but some of them were located in the dispensable genome. A significant fraction of horizontally transferred genes, virulence-related gene duplications, as well as different CRISPR arrays were found, which can explain the observed phenotypic differences. Finally, we found also, for the first time, the presence of a plasmid in one of the tested P. parmentieri strains isolated in Poland.

CONCLUSIONS: We can hypothesize that a large number of the genes in the dispensable genome and significant genomic variation among P. parmentieri strains could be the basis of the potential wide host range and widespread diffusion of P. parmentieri. The obtained data on the structure and gene content of P. parmentieri strains enabled us to speculate on the importance of high genomic plasticity for P. parmentieri adaptation to different environments.}, } @article {pmid30326841, year = {2018}, author = {Cadet, F and Fontaine, N and Vetrivel, I and Ng Fuk Chong, M and Savriama, O and Cadet, X and Charton, P}, title = {Application of fourier transform and proteochemometrics principles to protein engineering.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {382}, pmid = {30326841}, issn = {1471-2105}, mesh = {*Fourier Analysis ; Humans ; Protein Engineering/*methods ; Proteins/*chemistry ; }, abstract = {BACKGROUND: Connecting the dots between the protein sequence and its function is of fundamental interest for protein engineers. In-silico methods are useful in this quest especially when structural information is not available. In this study we propose a mutant library screening tool called iSAR (innovative Sequence Activity Relationship) that relies on the physicochemical properties of the amino acids, digital signal processing and partial least squares regression to uncover these sequence-function correlations.

RESULTS: We show that the digitalized representation of the protein sequence in the form of a Fourier spectrum can be used as an efficient descriptor to model the sequence-activity relationship of proteins. The iSAR methodology that we have developed identifies high fitness mutants from mutant libraries relying on physicochemical properties of the amino acids, digital signal processing and regression techniques. iSAR correlates variations caused by mutations in spectra with biological activity/fitness. It takes into account the impact of mutations on the whole spectrum and does not focus on local fitness alone. The utility of the method is illustrated on 4 datasets: cytochrome P450 for thermostability, TNF-alpha for binding affinity, GLP-2 for potency and enterotoxins for thermostability. The choice of the datasets has been made such as to illustrate the ability of the method to perform when limited training data is available and also when novel mutations appear in the test set, that have not been featured in the training set.

CONCLUSION: The combination of Fast Fourier Transform and Partial Least Squares regression is efficient in capturing the effects of mutations on the function of the protein. iSAR is a fast algorithm which can be implemented with limited computational resources and can make effective predictions even if the training set is limited in size.}, } @article {pmid30326838, year = {2018}, author = {Nigris, S and Baldan, E and Tondello, A and Zanella, F and Vitulo, N and Favaro, G and Guidolin, V and Bordin, N and Telatin, A and Barizza, E and Marcato, S and Zottini, M and Squartini, A and Valle, G and Baldan, B}, title = {Biocontrol traits of Bacillus licheniformis GL174, a culturable endophyte of Vitis vinifera cv. Glera.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {133}, pmid = {30326838}, issn = {1471-2180}, abstract = {BACKGROUND: Bacillus licheniformis GL174 is a culturable endophytic strain isolated from Vitis vinifera cultivar Glera, the grapevine mainly cultivated for the Prosecco wine production. This strain was previously demonstrated to possess some specific plant growth promoting traits but its endophytic attitude and its role in biocontrol was only partially explored. In this study, the potential biocontrol action of the strain was investigated in vitro and in vivo and, by genome sequence analyses, putative functions involved in biocontrol and plant-bacteria interaction were assessed.

RESULTS: Firstly, to confirm the endophytic behavior of the strain, its ability to colonize grapevine tissues was demonstrated and its biocontrol properties were analyzed. Antagonism test results showed that the strain could reduce and inhibit the mycelium growth of diverse plant pathogens in vitro and in vivo. The strain was demonstrated to produce different molecules of the lipopeptide class; moreover, its genome was sequenced, and analysis of the sequences revealed the presence of many protein-coding genes involved in the biocontrol process, such as transporters, plant-cell lytic enzymes, siderophores and other secondary metabolites.

CONCLUSIONS: This step-by-step analysis shows that Bacillus licheniformis GL174 may be a good biocontrol agent candidate, and describes some distinguished traits and possible key elements involved in this process. The use of this strain could potentially help grapevine plants to cope with pathogen attacks and reduce the amount of chemicals used in the vineyard.}, } @article {pmid30326837, year = {2018}, author = {Pian, C and Zhang, G and Wu, S and Li, F}, title = {Discovering the 'Dark matters' in expression data of miRNA based on the miRNA-mRNA and miRNA-lncRNA networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {379}, pmid = {30326837}, issn = {1471-2105}, support = {2016YFC1200600//National Key Research and Development Program/ ; V201308//The Science and Technology Research Project of the Ministry of Education/ ; }, mesh = {Gene Regulatory Networks/*genetics ; Humans ; MicroRNAs/*genetics ; RNA, Long Noncoding/*genetics ; }, abstract = {BACKGROUND: Since miRNAs can play important roles in different cancer types, how to discover cancer related miRNAs is an important issue. In general, the miRNAs with differential expression is the focus of attention. However, some important cancer related miRNAs are not excavated by differential expression analysis. We take this type of miRNAs as 'dark matters' (DM-miRNA). It is our great interests to develop an algorithm to discover DM-miRNAs.

RESULTS: An effective method was developed to find DM-miRNAs. This method is mainly for mining potential DM-miRNAs by building basic miRNA-mRNA network (BMMN) and miRNA-lncRNA network (BMLN). The results indicate that miRNA-mRNA and miRNA-lncRNA interactions can be used as novel cancer biomarkers.

CONCLUSIONS: The BMMN and BMLN can excavate the non-differentially expressed miRNAs which play an important role in the cancer. What's more, the edge biomarkers (miRNA-mRNA and miRNA-lncRNA interactions) contain more information than the node biomarkers. It will contribute to developing novel therapeutic candidates in cancers.}, } @article {pmid30326836, year = {2018}, author = {Zhang, YZ and Zhu, RW and Zhong, DL and Zhang, JQ}, title = {Nunataks or massif de refuge? A phylogeographic study of Rhodiola crenulata (Crassulaceae) on the world's highest sky islands.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {154}, pmid = {30326836}, issn = {1471-2148}, mesh = {Cell Nucleus/genetics ; China ; DNA, Chloroplast/genetics ; DNA, Ribosomal Spacer/genetics ; *Ecosystem ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; *Islands ; Phylogeny ; *Phylogeography ; Rhodiola/*classification ; Ribotyping ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: Quaternary climatic oscillations had tremendous effects on the current distribution of species. Here, we aim to elucidate the glacial history of Rhodiola crenulata, a perennial herb almost exclusively restricted to rock crevices on mountain peaks, and to test whether the nunatak or massif de refuge hypotheses could explain its distribution pattern.

RESULTS: Six haplotypes and six ribotypes were detected in the cpDNA data set and the ITS data set, respectively. The divergence of R. crenulata and its closest relatives was dated have occurred ca. 0.65 Mya, during the Naynayxungla glaciation on the QTP. Mismatch distribution analysis suggested that the species experienced a range expansion around 0.31 Mya. Populations with high genetic and haplotype diversity were found on the QTP platform as well in the Hengduan Mountains. The ecological niche modeling results showed that there were suitable habitats on both the QTP platform and in the Hengduan Mountains during the LGM.

CONCLUSION: Our results support a scenario that both nunataks and the massif de refuge hypotheses could explain the distribution of R. crenulata. We also confirmed that Quaternary climatic oscillations could promote plant speciation in some circumstances. This study adds to a growing body of evidence suggesting that the QTP plant lineages exhibited diverse reactions to the Quaternary climatic oscillations.}, } @article {pmid30326835, year = {2018}, author = {Li, Z and Zhu, M and Du, J and Ma, H and Jin, G and Dai, J}, title = {Genetic variants in nuclear DNA along with environmental factors modify mitochondrial DNA copy number: a population-based exome-wide association study.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {752}, pmid = {30326835}, issn = {1471-2164}, support = {BK20160095//Excellent Youth Foundation of Jiangsu/ ; PPZY2015A067//Top-notch Academic Programs Project of Jiangsu Higher Education Institutions/ ; }, mesh = {Adult ; Cell Nucleus/*genetics ; *DNA Copy Number Variations/drug effects ; DNA, Mitochondrial/*genetics ; *Environment ; Exome/*genetics ; Female ; *Genome-Wide Association Study ; Humans ; Leukocytes/drug effects/metabolism ; Male ; Middle Aged ; Molecular Sequence Annotation ; Particulate Matter/adverse effects ; Polymorphism, Single Nucleotide ; Smoking/adverse effects ; }, abstract = {BACKGROUND: Mitochondrial DNA (mtDNA) copy number has been found associated with multiple diseases, including cancers, diabetes and so on. Both environmental and genetic factors could affect the copy number of mtDNA. However, limited study was available about the relationship between genetic variants and mtDNA copy number. What's more, most of previous studies considered only environmental or genetic factors. Therefore, it's necessary to explore the genetic effects on mtDNA copy number with the consideration of PM2.5 exposure and smoking.

RESULTS: A multi-center population-based study was performed with 301 subjects from Zhuhai, Wuhan and Tianjin. Personal 24-h PM2.5 exposure levels, smoking and mtDNA copy number were evaluated. The Illumina Human Exome BeadChip, which contained 241,305 single nucleotide variants, was used for genotyping. The association analysis was conducted in each city and meta-analysis was adopted to combine the overall effect among three cities. Seven SNPs showed significant association with mtDNA copy number with P value less than 1.00E-04 after meta-analysis. The following joint analysis of our identified SNPs showed a significant allele-dosage association between the number of variants and mtDNA copy number (P = 5.02 × 10- 17). Further, 11 genes were identified associated with mtDNA copy number using gene-based analysis with a P value less than 0.01.

CONCLUSION: This study was the first attempt to evaluate the genetic effects on mtDNA copy number with the consideration of personal PM2.5 exposure level. Our findings could provide more evidences that genetic variants played important roles in modulating the copy number of mtDNA.}, } @article {pmid30326834, year = {2018}, author = {Hu, Y and Zhang, L and Wang, X and Sun, F and Kong, X and Dong, H and Xu, H}, title = {Two virulent sRNAs identified by genomic sequencing target the type III secretion system in rice bacterial blight pathogen.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {237}, pmid = {30326834}, issn = {1471-2229}, support = {31772247//National Natural Science Foundation of China/ ; 2017YFD0200901//national key research and development plan/ ; BK20150668//the Jiangsu Provincial Scientific Plan Program/ ; }, mesh = {Computational Biology ; Genome, Bacterial/*genetics ; High-Throughput Nucleotide Sequencing ; Mutation ; Oryza/*microbiology ; Plant Diseases/*microbiology ; RNA, Bacterial/genetics ; RNA, Small Untranslated/*genetics ; Sequence Analysis, RNA ; Tobacco/microbiology ; Type III Secretion Systems/*genetics ; Virulence/genetics ; Xanthomonas/genetics/*pathogenicity ; }, abstract = {BACKGROUND: Small non-coding RNA (sRNA) short sequences regulate various biological processes in all organisms, including bacteria that are animal or plant pathogens. Virulent or pathogenicity-associated sRNAs have been increasingly elucidated in animal pathogens but little is known about similar category of sRNAs in plant-pathogenic bacteria. This is particularly true regarding rice bacterial blight pathogen Xanthomonas oryzae pathovar oryzae (Xoo) as studies on the virulent role of Xoo sRNAs is very limited at present.

RESULTS: The number and genomic distribution of sRNAs in Xoo were determined by bioinformatics analysis based on high throughput sequencing (sRNA-Seq) of the bacterial cultures from virulence-inducing and standard growth media, respectively. A total of 601 sRNAs were identified in the Xoo genome and ten virulent sRNA candidates were screened out based on significant differences of their expression levels between the culture conditions. In addition, trans3287 and trans3288 were also selected as candidates due to high expression levels in both media. The differential expression of 12 sRNAs evidenced by the sRNA-Seq data was confirmed by a convincing quantitative method. Based on genetic analysis of Xoo ΔsRNA mutants generated by deletion of the 12 single sRNAs, trans217 and trans3287 were characterized as virulent sRNAs. They are essential not only for the formation of bacterial blight in a susceptible rice variety Nipponbare but also for the induction of hypersensitive response (HR) in nonhost plant tobacco. Xoo Δtrans217 and Δtrans3287 mutants fail to induce bacterial blight in Nipponbare and also fail to induce the HR in tobacco, whereas, genetic complementation restores both mutants to the wild type in the virulent performance and HR induction. Similar effects of gene knockout and complementation were found in the expression of hrpG and hrpX genes, which encode regulatory proteins of the type III secretion system. Consistently, secretion of a type III effector, PthXo1, is blocked in Δtrans217 or Δtrans3287 bacterial cultures but retrieved by genetic complementation to both mutants.

CONCLUSIONS: The genetic analysis characterizes trans217 and trans3287 as pathogenicity-associated sRNAs essential for the bacterial virulence on the susceptible rice variety and for the HR elicitation in the nonhost plant. The molecular evidence suggests that both virulent sRNAs regulate the bacterial virulence by targeting the type III secretion system.}, } @article {pmid30326833, year = {2018}, author = {Bacher, R and Leng, N and Chu, LF and Ni, Z and Thomson, JA and Kendziorski, C and Stewart, R}, title = {Trendy: segmented regression analysis of expression dynamics in high-throughput ordered profiling experiments.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {380}, pmid = {30326833}, issn = {1471-2105}, support = {U54 AI117924/AI/NIAID NIH HHS/United States ; R01 GM102756/GM/NIGMS NIH HHS/United States ; GM102756//National Institutes of Health/ ; 5U01HL099773//National Institutes of Health/ ; None//Marv Conney/ ; UH3 TR000506/TR/NCATS NIH HHS/United States ; U54 AI117924//National Institutes of Health/ ; 4UH3TR000506//National Institutes of Health/ ; U01 HL099773/HL/NHLBI NIH HHS/United States ; }, mesh = {Gene Expression Profiling/*methods ; High-Throughput Screening Assays/*methods ; Humans ; Software ; }, abstract = {BACKGROUND: High-throughput expression profiling experiments with ordered conditions (e.g. time-course or spatial-course) are becoming more common for studying detailed differentiation processes or spatial patterns. Identifying dynamic changes at both the individual gene and whole transcriptome level can provide important insights about genes, pathways, and critical time points.

RESULTS: We present an R package, Trendy, which utilizes segmented regression models to simultaneously characterize each gene's expression pattern and summarize overall dynamic activity in ordered condition experiments. For each gene, Trendy finds the optimal segmented regression model and provides the location and direction of dynamic changes in expression. We demonstrate the utility of Trendy to provide biologically relevant results on both microarray and RNA-sequencing (RNA-seq) datasets.

CONCLUSIONS: Trendy is a flexible R package which characterizes gene-specific expression patterns and summarizes changes of global dynamics over ordered conditions. Trendy is freely available on Bioconductor with a full vignette at https://bioconductor.org/packages/release/bioc/html/Trendy.html .}, } @article {pmid30326832, year = {2018}, author = {Li, W and Yang, Z and Yao, J and Li, J and Song, W and Yang, X}, title = {Cellulose synthase-like D1 controls organ size in maize.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {239}, pmid = {30326832}, issn = {1471-2229}, support = {2014CB147300//the National Basic Research '973' program of China/ ; }, mesh = {Alleles ; Chromosome Mapping ; Edible Grain ; *Genetic Variation ; Glucosyltransferases/genetics/*metabolism ; Organ Size/genetics ; Phenotype ; Plant Proteins/genetics/metabolism ; Quantitative Trait Loci/*genetics ; Zea mays/anatomy & histology/*enzymology/genetics ; }, abstract = {BACKGROUND: Plant architecture is a critical factor that affects planting density and, consequently, grain yield in maize. The genes or loci that determine organ size are the key regulators of plant architecture. Thus, understanding the genetic and molecular mechanisms of organ size will inform the use of a molecular manipulation approach to improve maize plant architecture and grain yield.

RESULTS: A total of 18 unique quantitative trait loci (QTLs) were identified for 11 agronomic traits in the F2 and F2:3 segregating populations derived from a cross between a double haploid line with a small plant architecture (MT03-1) and an inbred line with a large plant architecture (LEE-12). Subsequently, we showed that one QTL, qLW10, for multiple agronomic traits that relate to plant organ size reflects allelic variation in ZmCSLD1, which encodes a cellulose synthase-like D protein. ZmCSLD1 was localized to the trans-Golgi and was highly expressed in the rapidly growing regions. The loss of ZmCSLD1 function decreased cell division, which resulted in smaller organs with fewer cell numbers and, in turn, pleiotropic effects on multiple agronomic traits. In addition, intragenic complementation was investigated for two Zmcsld1 alleles with nonsynonymous SNPs in different functional domains, and the mechanism of this complementation was determined to be through homodimeric interactions.

CONCLUSIONS: Through positional cloning by using two populations and allelism tests, qLW10 for organ size was resolved to be a cellulose synthase-like D family gene, ZmCSLD1. ZmCSLD1 has pleiotropic effects on multiple agronomic traits that alter plant organ size by changing the process of cell division. These findings provide new insight into the regulatory mechanism that underlies plant organ development.}, } @article {pmid30326831, year = {2018}, author = {Akbarzadeh, A and Günther, OP and Houde, AL and Li, S and Ming, TJ and Jeffries, KM and Hinch, SG and Miller, KM}, title = {Developing specific molecular biomarkers for thermal stress in salmonids.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {749}, pmid = {30326831}, issn = {1471-2164}, mesh = {Animals ; Gene Expression Profiling ; Genetic Markers/*genetics ; Genetic Profile ; Gills/metabolism ; Heat-Shock Response/*genetics ; Salmonidae/*genetics/*physiology ; }, abstract = {BACKGROUND: Pacific salmon (Oncorhynchus spp.) serve as good biological indicators of the breadth of climate warming effects on fish because their anadromous life cycle exposes them to environmental challenges in both marine and freshwater environments. Our study sought to mine the extensive functional genomic studies in fishes to identify robust thermally-responsive biomarkers that could monitor molecular physiological signatures of chronic thermal stress in fish using non-lethal sampling of gill tissue.

RESULTS: Candidate thermal stress biomarkers for gill tissue were identified using comparisons among microarray datasets produced in the Molecular Genetics Laboratory, Pacific Biological Station, Nanaimo, BC, six external, published microarray studies on chronic and acute temperature stress in salmon, and a comparison of significant genes across published studies in multiple fishes using deep literature mining. Eighty-two microarray features related to 39 unique gene IDs were selected as candidate chronic thermal stress biomarkers. Most of these genes were identified both in the meta-analysis of salmon microarray data and in the literature mining for thermal stress markers in salmonids and other fishes. Quantitative reverse transcription PCR (qRT-PCR) assays for 32 unique genes with good efficiencies across salmon species were developed, and their activity in response to thermally challenged sockeye salmon (O. nerka) and Chinook salmon (O. tshawytscha) (cool, 13-14 °C and warm temperatures 18-19 °C) over 5-7 days was assessed. Eight genes, including two transcripts of each SERPINH1 and HSP90AA1, FKBP10, MAP3K14, SFRS2, and EEF2 showed strong and robust chronic temperature stress response consistently in the discovery analysis and both sockeye and Chinook salmon validation studies.

CONCLUSIONS: The results of both discovery analysis and gene expression showed that a panel of genes involved in chaperoning and protein rescue, oxidative stress, and protein biosynthesis were differentially activated in gill tissue of Pacific salmon in response to elevated temperatures. While individually, some of these biomarkers may also respond to other stressors or biological processes, when expressed in concert, we argue that a biomarker panel comprised of some or all of these genes could provide a reliable means to specifically detect thermal stress in field-caught salmon.}, } @article {pmid30326830, year = {2018}, author = {Matteoli, FP and Passarelli-Araujo, H and Reis, RJA and da Rocha, LO and de Souza, EM and Aravind, L and Olivares, FL and Venancio, TM}, title = {Genome sequencing and assessment of plant growth-promoting properties of a Serratia marcescens strain isolated from vermicompost.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {750}, pmid = {30326830}, issn = {1471-2164}, support = {E-26/111.827/2013//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; 449904/2014-8//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; PhD fellowship//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Biofilms ; Biological Transport/genetics ; Biomass ; *Composting ; Fusarium/growth & development ; Gene Transfer, Horizontal ; Genome, Bacterial/*genetics ; Manure/microbiology ; Pest Control, Biological ; Phenols/metabolism ; Phosphorus/chemistry/metabolism ; Serratia marcescens/*genetics/isolation & purification/metabolism/*physiology ; Solubility ; Spermidine/biosynthesis ; Zea mays/*growth & development/*microbiology ; Zinc/chemistry/metabolism ; }, abstract = {BACKGROUND: Plant-bacteria associations have been extensively studied for their potential in increasing crop productivity in a sustainable manner. Serratia marcescens is a species of Enterobacteriaceae found in a wide range of environments, including soil.

RESULTS: Here we describe the genome sequencing and assessment of plant growth-promoting abilities of S. marcescens UENF-22GI, a strain isolated from mature cattle manure vermicompost. In vitro, S. marcescens UENF-22GI is able to solubilize P and Zn, to produce indole compounds (likely IAA), to colonize hyphae and counter the growth of two phytopathogenic fungi. Inoculation of maize with this strain remarkably increased seedling growth and biomass under greenhouse conditions. The S. marcescens UENF-22GI genome has 5 Mb, assembled in 17 scaffolds comprising 4662 genes (4528 are protein-coding). No plasmids were identified. S. marcescens UENF-22GI is phylogenetically placed within a clade comprised almost exclusively of non-clinical strains. We identified genes and operons that are likely responsible for the interesting plant-growth promoting features that were experimentally described. The S. marcescens UENF-22GI genome harbors a horizontally-transferred genomic island involved in antibiotic production, antibiotic resistance, and anti-phage defense via a novel ADP-ribosyltransferase-like protein and possible modification of DNA by a deazapurine base, which likely contributes to its competitiveness against other bacteria.

CONCLUSIONS: Collectively, our results suggest that S. marcescens UENF-22GI is a strong candidate to be used in the enrichment of substrates for plant growth promotion or as part of bioinoculants for agriculture.}, } @article {pmid30326829, year = {2018}, author = {Zhang, T and Lv, W and Zhang, H and Ma, L and Li, P and Ge, L and Li, G}, title = {Genome-wide analysis of the basic Helix-Loop-Helix (bHLH) transcription factor family in maize.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {235}, pmid = {30326829}, issn = {1471-2229}, support = {2014CB147301//the State Key Basic Research/ ; 2016YFD0101003//Development Program of China/ ; ZR2014CQ055//the Natural Science Foundation of Shandong Province/ ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Chromosomes, Plant/*genetics ; Gene Regulatory Networks ; Genome, Plant/*genetics ; Introns/genetics ; Phylogeny ; Plant Leaves/genetics ; Plant Roots/genetics ; Promoter Regions, Genetic/genetics ; Seeds/genetics ; Sequence Alignment ; Zea mays/*genetics ; }, abstract = {BACKGROUND: In plants, the basic helix-loop-helix (bHLH) transcription factors play key roles in diverse biological processes. Genome-wide comprehensive and systematic analyses of bHLH proteins have been well conducted in Arabidopsis, rice, tomato and other plant species. However, only few of bHLH family genes have been functional characterized in maize.

RESULTS: In this study, our genome-wide analysis identified 208 putative bHLH family proteins (ZmbHLH proteins) in maize (Zea mays). We classified these proteins into 18 subfamilies by comparing the ZmbHLHs with Arabidopsis thaliana bHLH proteins. Phylogenetic analysis, conserved protein motifs, and exon-intron patterns further supported the evolutionary relationships among these bHLH proteins. Genome distribution analysis found that the 208 ZmbHLH loci were located non-randomly on the ten maize chromosomes. Further, analysis of conserved cis-elements in the promoter regions, protein interaction networks, and expression patterns in roots, leaves, and seeds across developmental stages, suggested that bHLH family proteins in maize are probably involved in multiple physiological processes in plant growth and development.

CONCLUSION: We performed a genome-wide, systematic analysis of bHLH proteins in maize. This comprehensive analysis provides a useful resource that enables further investigation of the physiological roles and molecular functions of the ZmbHLH transcription factors.}, } @article {pmid30326828, year = {2018}, author = {Kranz, A and Steinmann, A and Degner, U and Mengus-Kaya, A and Matamouros, S and Bott, M and Polen, T}, title = {Global mRNA decay and 23S rRNA fragmentation in Gluconobacter oxydans 621H.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {753}, pmid = {30326828}, issn = {1471-2164}, support = {No. 313/323-400-002 13//Ministry of Innovation, Science and Research within the framework of the NRW Strategieprojekt BioSC/ ; }, mesh = {Gluconobacter oxydans/*genetics ; Half-Life ; *RNA Stability ; RNA, Bacterial/*chemistry/*metabolism ; RNA, Messenger/chemistry/*metabolism ; RNA, Ribosomal, 23S/*chemistry/*metabolism ; Ribosomes/metabolism ; }, abstract = {BACKGROUND: Gluconobacter oxydans is a strictly aerobic Gram-negative acetic acid bacterium used industrially for oxidative biotransformations due to its exceptional type of catabolism. It incompletely oxidizes a wide variety of carbohydrates regio- and stereoselectively in the periplasm using membrane-bound dehydrogenases with accumulation of the products in the medium. As a consequence, only a small fraction of the carbon and energy source enters the cell, resulting in a low biomass yield. Additionally, central carbon metabolism is characterized by the absence of a functional glycolysis and absence of a functional tricarboxylic acid (TCA) cycle. Due to these features, G. oxydans is a highly interesting model organism. Here we analyzed global mRNA decay in G. oxydans to describe its characteristic features and to identify short-lived mRNAs representing potential bottlenecks in the metabolism for further growth improvement by metabolic engineering.

RESULTS: Using DNA microarrays we estimated the mRNA half-lives in G. oxydans. Overall, the mRNA half-lives ranged mainly from 3 min to 25 min with a global mean of 5.7 min. The transcripts encoding GroES and GroEL required for proper protein folding ranked at the top among transcripts exhibiting both long half-lives and high abundance. The F-type H+-ATP synthase transcripts involved in energy metabolism ranked among the transcripts with the shortest mRNA half-lives. RNAseq analysis revealed low expression levels for genes of the incomplete TCA cycle and also the mRNA half-lives of several of those were short and below the global mean. The mRNA decay analysis also revealed an apparent instability of full-length 23S rRNA. Further analysis of the ribosome-associated rRNA revealed a 23S rRNA fragmentation pattern exhibiting new cleavage regions in 23S rRNAs which were previously not known.

CONCLUSIONS: The very short mRNA half-lives of the H+-ATP synthase, which is likely responsible for the ATP-proton motive force interconversion in G. oxydans under many or most conditions, is notably in contrast to mRNA decay data from other bacteria. Together with the short mRNA half-lives and low expression of some other central metabolic genes it could limit intended improvements of G. oxydans' biomass yield by metabolic engineering. Also, further studies are needed to unravel the multistep process of the 23S rRNA fragmentation in G. oxydans.}, } @article {pmid30326406, year = {2018}, author = {Siddique, S and Grundler, FM}, title = {Parasitic nematodes manipulate plant development to establish feeding sites.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {102-108}, doi = {10.1016/j.mib.2018.09.004}, pmid = {30326406}, issn = {1879-0364}, abstract = {Cyst and root-knot nematodes, the two economically most important groups of plant parasitic nematodes, induce neoplastic feeding sites in the roots of their host plants. The formation of feeding sites is accompanied by large-scale transcriptomic, metabolomic, and structural changes in host plants. However, the mechanisms that lead to such remarkable changes have remained poorly understood until recently. Now, genomic and genetic analyses have greatly enhanced our understanding of all aspects of plant-nematode interaction. Here, we review some of the recent advances in understanding cyst and root-knot nematode parasitism. In particular, we highlight new findings on the role of plant hormones and small RNAs in nematode feeding site formation and function. Finally, we touch on our emerging understanding of the function of nematode-associated secretions.}, } @article {pmid30326288, year = {2019}, author = {Tong, Y and Binford, G and Rheims, CA and Kuntner, M and Liu, J and Agnarsson, I}, title = {Huntsmen of the Caribbean: Multiple tests of the GAARlandia hypothesis.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {259-268}, doi = {10.1016/j.ympev.2018.09.017}, pmid = {30326288}, issn = {1095-9513}, abstract = {The origin of the Caribbean biota remains debated, but amassing evidence suggests important roles of both dispersal and vicariance events in the colonization the archipelago. The most prominent vicariance hypothesis is colonization over the GAARlandia land bridge that putatively connected the Greater Antilles to South America around 33 mya. This hypothesis has received support from studies of individual lineages, but its main prediction-the simultaneous colonization of multiple lineages during that time window-requires further unambiguous corroboration. Here, we examine the phylogenetic structure of huntsman spiders (Sparassidae) of the Caribbean. Huntsman spiders are appropriate models for this question, as they are expected to be dispersal limited as substrate and foliage dwelling spiders that rarely balloon, yet are found on some volcanic islands, and thus at least some overwater dispersal must have occurred. We focus on the Caribbean endemic Neostasina, but also include Caribbean Olios, for a deeper biogeographical understanding. We use two mitochondrial and four nuclear markers to reconstruct dated phylogenetic trees and to test taxonomic and biogeographic hypotheses. Our analyses strongly support the monophyly of Neostasina and the polyphyly of Olios, with a new clade endemic to the Caribbean. Both Neostasina and Caribbean Olios occur on the Greater and Lesser Antilles and independently colonized the Caribbean around 36-28 mya. Hypothesis testing in BioGeoBEARS suggests a role of the GAARlandia landbridge in the colonization of both clades. The 'Olios-like' clade, in contrast, is restricted to the southern Lesser Antilles and shows a biogeographic history consistent with colonization from S. America, probably within the last 10 my. Thus, many spider lineages on the Greater Antilles seem to have colonized the Caribbean during a relatively short time span approximately coinciding with the proposed timing of GAARlandia. The synchronous colonization of multiple lineages suggests a temporary land connection. However, the main problem in concluding synchronous events across lineages in this study, as in most others, is the ambiguity in chronogram analyses meaning that many different patterns can be 'consistent' with GAARlandia, thus potentially providing a false positive result. Broad comparative biogeographical studies such as the CarBio project will offer the best opportunity to multiply test shared biogeographic patterns among independent lineages. The current paper contributes evidence from multiple lineages that will contribute to this synthesis.}, } @article {pmid30326287, year = {2019}, author = {Bossert, S and Murray, EA and Almeida, EAB and Brady, SG and Blaimer, BB and Danforth, BN}, title = {Combining transcriptomes and ultraconserved elements to illuminate the phylogeny of Apidae.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {121-131}, doi = {10.1016/j.ympev.2018.10.012}, pmid = {30326287}, issn = {1095-9513}, abstract = {Two increasingly popular approaches to reconstruct the Tree of Life involve whole transcriptome sequencing and the target capture of ultraconserved elements (UCEs). Both methods can be used to generate large, multigene datasets for analysis of phylogenetic relationships in non-model organisms. While targeted exon sequencing across divergent lineages is now a standard method, it is still not clear if UCE data can be readily combined with published transcriptomes. In this study, we evaluate the combination of UCEs and transcriptomes in a single analysis using genome-, transcriptome-, and UCE data for 79 bees in the largest and most biologically diverse bee family, Apidae. Using existing tools, we first developed a workflow to assemble phylogenomic data from different sources and produced two large nucleotide matrices of combined data. We then reconstructed the phylogeny of the Apidae using concatenation- and coalescent-based methods, and critically evaluated the resulting phylogenies in the context of previously published genetic, genomic, and morphological data sets. Our estimated phylogenetic trees are robustly supported and largely congruent with previous molecular hypotheses, from deep nodes to shallow species-level phylogenies. Moreover, the combined approach allows us to resolve controversial nodes of the apid Tree of Life, by clarifying the relationships among the genera of orchid bees (Euglossini) and the monophyly of the Centridini. Additionally, we present novel phylogenetic evidence supporting the monophyly of the diverse clade of cleptoparasitic Apidae and the placement of two enigmatic, oil-collecting genera (Ctenoplectra and Tetrapedia). Lastly, we propose a revised classification of the family Apidae that reflects our improved understanding of apid higher-level relationships.}, } @article {pmid30326286, year = {2018}, author = {Luíza Silva-Luz, C and Rubens Pirani, J and Daniel Mitchell, J and Daly, D and do Valle Capelli, N and Demarco, D and Pell, SK and Plunkett, GM}, title = {Phylogeny of Schinus L. (Anacardiaceae) with a new infrageneric classification and insights into evolution of spinescence and floral traits.}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ympev.2018.10.013}, pmid = {30326286}, issn = {1095-9513}, abstract = {Schinus, best known by its few cultivated and invasive species, is the largest genus of Anacardiaceae in southern South America. It is remarkably diverse compared to closely related genera, with approximately 42 species, most of which occur in several arid vegetation types and extend into Andean and Atlantic moist forests. The most comprehensive taxonomic revision of the genus dates to 1957, recognizing S. subg. Schinus and S. subg. Duvaua, the latter of which were further divided into two sections. Subsequent studies have highlighted morphological inconsistencies in this infrageneric classification, and species delimitation remains a challenge. Schinus has been poorly sampled in previous phylogenetic studies of Anacardiaceae, and thus any assumptions about its monophyly and relationships remain untested. We investigated the phylogenetic relationships of 44 Schinus taxa and sampled 122 specimens, including the outgroup, using nine nuclear and two plastid DNA sequence regions, most of them developed recently for Commiphora (Burseraceae, sister to Anacardiaceae). We used maximum parsimony, maximum likelihood, and Bayesian inference to infer relationships among species. We also constructed a morphological dataset, including vegetative anatomical features, and compared these characters to hypotheses based on molecular evidence in order to achieve a better understanding of the relationships among the species of Schinus and to related genera, aiming also to identify morphological characters and putative synapomorphies for major clades, and to discuss hypotheses regarding the evolution of structural traits in the genus. Our analyses strongly support the monophyly of Schinus, but also indicate that S. subg. Schinus and the sections of S. subg. Duvaua are polyphyletic. The phylogenetic relationships that emerged from our analyses include eight relatively well-supported lineages, but relationships among closely related species remain unclear in some clades. Ancestral state reconstructions demonstrate that several morphological and leaf-anatomical characters are valuable in characterizing some lineages. By contrast, most of the traits that have traditionally been used to circumscribe groups in Schinus show high levels of homoplasy. In light of these results, we present a novel sectional classification of Schinus based on a combination of character states associated with geographic distribution, corresponding to lineages that are mostly allopatric or at least ecologically distinct.}, } @article {pmid30326285, year = {2019}, author = {Schäfer, GG and Pedrini-Martha, V and Schnegg, R and Dallinger, R and Jackson, DJ and Lieb, B}, title = {Hemocyanin genes as indicators of habitat shifts in Panpulmonata?.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {99-103}, doi = {10.1016/j.ympev.2018.10.014}, pmid = {30326285}, issn = {1095-9513}, abstract = {Hemocyanin is the primary respiratory protein for the majority of the Mollusca and therefore directly interfaces with the physiological requirements of each species and the environments to which they are adapted. Hemocyanin is therefore likely to have been evolutionarily imprinted by significant habitat shifts. In the gastropod clade Panpulmonata (>30,000 species) major realm transitions have occurred multiple times independently and may have contributed to the diversification of this group. Yet, little is known about the adaptive changes linked to these habitat shifts. In order to gain deeper insight into the evolution of panpulmonate hemocyanins and to infer possible impacts associated with those scenarios, we have assembled and analysed hemocyanin isoforms from 4 panpulmonate species: (i) Helix pomatia, (ii) Cantareus aspersus (both Helicidae, Stylommatophora), (iii) Arion vulgaris (Arionidae, Stylommatophora) and (iv) Lymnaea stagnalis (Lymnaeidae, Hygrophila). Additionally, we describe a new hemocyanin isoform within the genome of the euopisthobranch Aplysia californica. Using these newly acquired hemocyanin data, we performed a phylogenetic analysis that reveals independent duplication events of hemocyanin within lineages that correlate with significant habitat shifts.}, } @article {pmid30326183, year = {2018}, author = {Hardy, K and Buckley, S and Copeland, L}, title = {Pleistocene dental calculus: Recovering information on Paleolithic food items, medicines, paleoenvironment and microbes.}, journal = {Evolutionary anthropology}, volume = {27}, number = {5}, pages = {234-246}, doi = {10.1002/evan.21718}, pmid = {30326183}, issn = {1520-6505}, mesh = {Animals ; Cooking ; Dental Calculus/*chemistry/history/*microbiology ; Diet/*history ; Environment ; Fossils ; History, Ancient ; Hominidae ; Neanderthals ; Starch/chemistry ; Vegetables/chemistry ; }, abstract = {Dental calculus is now widely used to recover information on items ingested in the past. It is particularly valuable in the earlier Paleolithic, where recovered data may represent the only evidence for plant use. Several recovery methods are used and each one produces different results. Biomolecular markers and genetic material recovered from dental calculus is providing new data on identifiable dietary and medicinal items and human microbial communities. The recovery of microfossils, in particular, starch granules, has triggered a new awareness of the role of plants in the diet throughout the Paleolithic. However, the minute amount of material recovered has little relationship with food eaten during a person's life, while salivary amylase breaks down cooked starch. Therefore, broader dietary interpretations and detection of cooked food are problematic. The study of ancient dental calculus holds great potential to recover information about past lives, within realistic parameters.}, } @article {pmid30325554, year = {2018}, author = {Robbins, MM and Robbins, AM}, title = {Variation in the social organization of gorillas: Life history and socioecological perspectives.}, journal = {Evolutionary anthropology}, volume = {27}, number = {5}, pages = {218-233}, doi = {10.1002/evan.21721}, pmid = {30325554}, issn = {1520-6505}, support = {//Max Planck Society/ ; }, mesh = {Animals ; Anthropology ; *Biological Evolution ; Female ; Gorilla gorilla/*physiology ; Male ; *Social Behavior ; }, abstract = {A focus of socioecological research is to understand how ecological, social, and life history factors influence the variability of social organization within and between species. The genus Gorilla exhibits variability in social organization with western gorilla groups being almost exclusively one-male, yet approximately 40% of mountain gorilla groups are multimale. We review five ultimate causes for the variability in social organization within and among gorilla populations: human disturbance, ecological constraints on group size, risk of infanticide, life history patterns, and population density. We find the most evidence for the ecological constraints and life history hypotheses, but an over-riding explanation remains elusive. The variability may hinge on variation in female dispersal patterns, as females seek a group of optimal size and with a good protector male. Our review illustrates the challenges of understanding why the social organization of closely related species may deviate from predictions based on socioecological and life history theory.}, } @article {pmid30325443, year = {2018}, author = {Skaldin, M and Tuittila, M and Zavialov, AV and Zavialov, AV}, title = {Secreted Bacterial Adenosine Deaminase Is an Evolutionary Precursor of Adenosine Deaminase Growth Factor.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2851-2861}, doi = {10.1093/molbev/msy193}, pmid = {30325443}, issn = {1537-1719}, abstract = {Adenosine deaminases (ADAs) play a pivotal role in regulating the level of adenosine, an important signaling molecule that controls a variety of cellular responses. Two distinct ADAs, ADA1 and adenosine deaminase growth factor (ADGF aka ADA2), are known. Cytoplasmic ADA1 plays a key role in purine metabolism and is widely distributed from prokaryotes to mammals. On the other hand, secreted ADGF/ADA2 is a cell-signaling protein that was thought to be present only in multicellular organisms. Here, we discovered a bacterial homologue of ADGF/ADA2. Bacterial and eukaryotic ADGF/ADA2 possess the dimerization and PRB domains characteristic for the family, have nearly identical catalytic sites, and show similar catalytic characteristics. Most surprisingly, the bacterial enzyme has a signal sequence similar to that of eukaryotic ADGF/ADA2 and is specifically secreted into the extracellular space, where it may potentially control the level of extracellular adenosine. This finding provides the first example of evolution of an extracellular eukaryotic signaling protein from a secreted bacterial analogue with identical activity and suggests a potential role of ADGF/ADA2 in bacterial communication.}, } @article {pmid30325298, year = {2018}, author = {Dong, X and Zhang, G and Xiong, Q and Liu, D and Wang, D and Liu, Y and Wu, G and Li, P and Luo, Y and Zhang, R}, title = {Paracoccus salipaludis sp. nov., isolated from saline-alkaline soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3812-3817}, doi = {10.1099/ijsem.0.003065}, pmid = {30325298}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Paracoccus/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salinity ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, short ovoid- to coccus-shaped, aerobic, non-flagellated, and nonmotile strain, designated WN007T, was isolated from the natural saline-alkali wetland soil. Growth occurred at 10-45 °C (optimum 33-37 °C), pH 6.5-10.0 (optimum, pH 7.5-8.0) and with 0-15 % (w/v) NaCl (optimum, 2-4 % NaCl). Catalase- and oxidase-positive. A comparison of the 16S rRNA gene sequence of WN007T showed the highest sequence similarities to Paracoccus chinensis (97.5 %) and Paracoccus niistensis (97.4 %). The major respiratory quinone of strain WN007T was Q10 and the fatty acid profile of strain WN007T contained a predominant amount of summed feature 7 and small quantities of C10 : 0 3OH, C16 : 00 and C18 : 00. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, glycolipid, aminolipid and lipid. The genome revealed that the G+C content was 63.9 mol% and the DNA-DNA relatedness values between strain WN007T and the type strains of P. chinensis CGMCC 1.7655Tand P. niistensis KCTC 22789T were 46.9±2.3 and 42.4±1.7 %, respectively. This was also confirmed by the low average nucleotide identity values (<83.5 %) between strain WN007T and the most closely related recognized Paracoccus species. According to these results, strain WN007T represents a novel species of the genus Paracoccus, for which the name Paracoccussalipaludis sp. nov. is proposed. The type strain is WN007T (=KCTC 52851T=ACCC 19972T).}, } @article {pmid30325296, year = {2018}, author = {Sun, C and Xu, L and Yu, XY and Zhao, Z and Wu, YH and Oren, A and Wang, CS and Xu, XW}, title = {Minwuia thermotolerans gen. nov., sp. nov., a marine bacterium forming a deep branch in the Alphaproteobacteria, and proposal of Minwuiaceae fam. nov. and Minwuiales ord. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3856-3862}, doi = {10.1099/ijsem.0.003073}, pmid = {30325296}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {Two Gram-stain-negative, strictly aerobic, non-motile, non-spore-forming, rod-shaped bacteria, designated as SY3-15Tand SY3-13, were isolated from a seawater sample of the South China Sea. Colonies were 0.5-1.0 mm in diameter, smooth, circular, convex and translucent after growth on marine agar at 37 °C for 3 days. The strains were found to grow at 20-50 °C (optimum, 42 °C), pH 6.0-8.5 (optimum, pH 6.5-7.5) and with 0.5-6.0 % (w/v) NaCl (optimum, 1.5-2.0 %). Chemotaxonomic analysis showed the sole respiratory quinone to be ubiquinone-10, the major fatty acids (>10 %) were C16 : 0 3-OH, C19 : 0cyclo ω9c, C18 : 1 3-OH and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), and the polar lipids were phosphatidylglycerol, two unidentified aminolipids and three unidentified lipids. The DNA G+C content was 67.2-67.4 mol% calculated by genome. The 16S rRNA gene sequences of strains SY3-15T and SY3-13 were identical and related to the genus Lutibaculum with a similarity of 92.1 %. The 16S rRNA gene phylogenetic trees reconstructed with neighbour-joining, maximum-parsimony and minimum-evolution methods showed that the strains constituted a deep and separated branch from other families of Alphaproteobacteria, and the phylogenetic trees based on concatenated 163 protein sequences from genome sequences showed that the clade in which strains SY3-15T and SY3-13 located was separated from the clade of the other orders of Alphaproteobacteria, indicating it may represent a novel family of a novel order. Based on their phenotypic properties and their phylogenetic distinctiveness, we propose strains SY3-15T (=MCCC 1K03467T=KCTC 62335T) and SY3-13 (=MCCC 1K03466=KCTC 62329) to represent a novel species of a novel genus with the name Minwuia thermotolerans gen. nov., sp. nov., and we propose Minwuiaceae fam. nov. and Minwuiales ord. nov. with Minwuia as the type genus.}, } @article {pmid30325294, year = {2018}, author = {Kittisrisopit, S and Pittayakhajonwut, P and Tadtong, S and Thawai, C}, title = {Microbispora soli sp. nov., isolated from soil of a hot spring.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3863-3868}, doi = {10.1099/ijsem.0.003075}, pmid = {30325294}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Hot Springs/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, strain RTBAU4-9T, which produced longitudinally paired spores on aerial mycelia, was isolated from a soil sample of a hot spring area. This strain exhibited chemotaxonomic and genotypic properties typical of the genus Microbispora, such as meso-diaminopimelic acid in the cell-wall peptidoglycan, glucose, ribose and trace amount of madurose as the characteristic whole-cell sugars, phosphatidylethanolamine, diphosphatidylglycerol and phosphoglycolipids as the membrane phospholipids, MK-9(H4), MK-9(H2) and MK-9(H0) as the characteristic menaquinones, and iso-C16 : 0 and anteiso-C17 : 0 as the main fatty acids. The G+C content of the genomic DNA was 70.2 mol%. The result of 16S rRNA gene sequence analysis revealed the strain was a member of the genus Microbispora and was most closely related to Microbispora hainanensis 211020T (98.3 % 16S rRNA gene sequence similarity). In addition, the low percentage of DNA-DNA relatedness (<28.1±1.2 %) and several phenotypic differences confirmed that strain RTBAU4-9T should be considered as representing a novel species of the genus Microbispora, for which the name Microbispora soli sp. nov. is proposed. The type strain is RTBAU4-9T (=TBRC 7648T=NBRC 113147T).}, } @article {pmid30325293, year = {2018}, author = {Dedysh, SN and Yilmaz, P}, title = {Refining the taxonomic structure of the phylum Acidobacteria.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3796-3806}, doi = {10.1099/ijsem.0.003062}, pmid = {30325293}, issn = {1466-5034}, mesh = {Acidobacteria/*classification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The phylum Acidobacteria was created in 1997 in order to accommodate a large number of 16S rRNA gene sequences retrieved from various environments in cultivation-independent studies. At present, 26 major sequence clades or subdivisions (SDs) are recognized within this phylum, but only seven of them (SDs 1, 3, 4, 6, 8, 10 and 23) are commonly addressed as containing taxonomically described representatives. Here, we examined the currently explored diversity within the Acidobacteria using the candidate taxonomic unit circumscription system. Based on this analysis, 26 subdivisions were assigned to 15 class-level units, five of which contain described members. These include three earlier established classes Acidobacteriia, Blastocatellia and Holophagae, as well as two as-yet-undescribed groups defined by SDs 6 and 23, which we propose to name Vicinamibacteria classis nov. and Thermoanaerobaculia classis nov., respectively. The former assignment of Thermotomaculum hydrothermale to SD10 was found to be incorrect. This bacterium, therefore, was placed in the family Thermotomaculaceae fam. nov., order Thermotomaculales ord. nov. within the class Holophagae. We also propose establishing a number of high-level taxa to accommodate described representatives of SDs 3, 4, 6 and 23. The family Bryobacteraceae of SD3 Acidobacteria is placed in the order Bryobacterales ord. nov. within the taxonomic range of the class Acidobacteriia. The order Vicinamibacteriales ord. nov. is proposed to accommodate the family Vicinamibacteriaceae of SD6 Acidobacteria. Finally, the family Thermoanaerobaculaceae fam. nov., the order Thermoanaerobaculales ord. nov. are proposed to accommodate the only described representative of SD23, Thermoanaerobaculum aquaticum.}, } @article {pmid30325092, year = {2019}, author = {Zhang, SY and Tsementzi, D and Hatt, JK and Bivins, A and Khelurkar, N and Brown, J and Tripathi, SN and Konstantinidis, KT}, title = {Intensive allochthonous inputs along the Ganges River and their effect on microbial community composition and dynamics.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {182-196}, doi = {10.1111/1462-2920.14439}, pmid = {30325092}, issn = {1462-2920}, support = {//Georgia Institute of Technology/ ; DEB 1241046//National Science Foundation/ ; }, abstract = {Little is known about microbial communities in the Ganges River, India and how they respond to intensive anthropogenic inputs. Here we applied shotgun metagenomics sequencing to study microbial community dynamics and function in planktonic samples collected along an approximately 700 km river transect, including urban cities and rural settings in upstream waters, before and after the monsoon rainy season. Our results showed that 11%-32% of the microbes represented terrestrial, sewage and human inputs (allochthonous). Sewage inputs significantly contributed to the higher abundance, by 13-fold of human gut microbiome (HG) associated sequences and 2-fold of antibiotic resistance genes (ARGs) in the Ganges relative to other riverine ecosystems in Europe, North and South America. Metagenome-assembled genome sequences (MAGs) representing allochthonous populations were detectable and tractable across the river after 1-2 days of (downstream) transport (> 200 km apart). Only approximately 8% of these MAGs were abundant in U.S. freshwater ecosystems, revealing distinct biodiversity for the Ganges. Microbial communities in the rainy season exhibited increased alpha-diversity and spatial heterogeneity and showed significantly weaker distance-decay patterns compared with the dry season. These results advance our understanding of the Ganges microbial communities and how they respond to anthropogenic pollution.}, } @article {pmid30323930, year = {2018}, author = {Buschman, AR and Rep, A}, title = {Pre-eclampsia: Understanding clinical complexity.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {211-212}, pmid = {30323930}, issn = {2050-6201}, } @article {pmid30323887, year = {2018}, author = {López-Leal, G and Cornejo-Granados, F and Hurtado-Ramírez, JM and Mendoza-Vargas, A and Ochoa-Leyva, A}, title = {Functional and taxonomic classification of a greenhouse water drain metagenome.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {20}, pmid = {30323887}, issn = {1944-3277}, abstract = {Microbiome sequencing has become the standard procedure in the study of new ecological and human-constructed niches. To our knowledge, this is the first report of a metagenome from the water of a greenhouse drain. We found that the greenhouse is not a diverse niche, mainly dominated by Rhizobiales and Rodobacterales. The analysis of the functions encoded in the metagenome showed enrichment of characteristic features of soil and root-associated bacteria such as ABC-transporters and hydrolase enzymes. Additionally, we found antibiotic resistances genes principally for spectinomycin, tetracycline, and aminoglycosides. This study aimed to identify the bacteria and functional gene composition of a greenhouse water drain sample and also provide a genomic resource to search novel proteins from a previously unexplored niche. All the metagenome proteins and their annotations are available to the scientific community via http://microbiomics.ibt.unam.mx/tools/metagreenhouse/.}, } @article {pmid30323312, year = {2018}, author = {Rees, HA and Liu, DR}, title = {Base editing: precision chemistry on the genome and transcriptome of living cells.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {770-788}, doi = {10.1038/s41576-018-0059-1}, pmid = {30323312}, issn = {1471-0064}, support = {R01 EB022376/EB/NIBIB NIH HHS/United States ; }, abstract = {RNA-guided programmable nucleases from CRISPR systems generate precise breaks in DNA or RNA at specified positions. In cells, this activity can lead to changes in DNA sequence or RNA transcript abundance. Base editing is a newer genome-editing approach that uses components from CRISPR systems together with other enzymes to directly install point mutations into cellular DNA or RNA without making double-stranded DNA breaks. DNA base editors comprise a catalytically disabled nuclease fused to a nucleobase deaminase enzyme and, in some cases, a DNA glycosylase inhibitor. RNA base editors achieve analogous changes using components that target RNA. Base editors directly convert one base or base pair into another, enabling the efficient installation of point mutations in non-dividing cells without generating excess undesired editing by-products. In this Review, we summarize base-editing strategies to generate specific and precise point mutations in genomic DNA and RNA, highlight recent developments that expand the scope, specificity, precision and in vivo delivery of base editors and discuss limitations and future directions of base editing for research and therapeutic applications.}, } @article {pmid30323288, year = {2018}, author = {Ma, J and Shrestha, R and Adelberg, J and Yeh, CY and Hossain, Z and Knightly, E and Jornet, JM and Mittleman, DM}, title = {Security and eavesdropping in terahertz wireless links.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {89-93}, doi = {10.1038/s41586-018-0609-x}, pmid = {30323288}, issn = {1476-4687}, abstract = {Resiliency against eavesdropping and other security threats has become one of the key design considerations for communication systems. As wireless systems become ubiquitous, there is an increasing need for security protocols at all levels, including software (such as encryption), hardware (such as trusted platform modules) and the physical layer (such as wave-front engineering)1-5. With the inevitable shift to higher carrier frequencies, especially in the terahertz range (above 100 gigahertz), an important consideration is the decreased angular divergence (that is, the increased directionality) of transmitted signals, owing to the reduced effects of diffraction on waves with shorter wavelengths. In recent years, research on wireless devices6-8 and systems9-11 that operate at terahertz frequencies has ramped up markedly. These high-frequency, narrow-angle broadcasts present a more challenging environment for eavesdroppers compared to the wide-area broadcasts used at lower frequencies12,13. However, despite the widespread assumption of improved security for high-frequency wireless data links14-16, the possibility of terahertz eavesdropping has not yet been characterized. A few recent studies have considered the issue at lower frequencies5,12,13,17,18, but generally with the idea that the eavesdropper's antenna must be located within the broadcast sector of the transmitting antenna, leading to the conclusion that eavesdropping becomes essentially impossible when the transmitted signal has sufficiently high directionality15. Here we demonstrate that, contrary to this expectation, an eavesdropper can intercept signals in line-of-sight transmissions, even when they are transmitted at high frequencies with narrow beams. The eavesdropper's techniques are different from those for lower-frequency transmissions, as they involve placing an object in the path of the transmission to scatter radiation towards the eavesdropper. We also discuss one counter-measure for this eavesdropping technique, which involves characterizing the backscatter of the channel. We show that this counter-measure can be used to detect some, although not all, eavesdroppers. Our work highlights the importance of physical-layer security in terahertz wireless networks and the need for transceiver designs that incorporate new counter-measures.}, } @article {pmid30323287, year = {2018}, author = {Taylor, MT and Nelson, JE and Suero, MG and Gaunt, MJ}, title = {A protein functionalization platform based on selective reactions at methionine residues.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {563-568}, pmid = {30323287}, issn = {1476-4687}, abstract = {Nature has a remarkable ability to carry out site-selective post-translational modification of proteins, therefore enabling a marked increase in their functional diversity1. Inspired by this, chemical tools have been developed for the synthetic manipulation of protein structure and function, and have become essential to the continued advancement of chemical biology, molecular biology and medicine. However, the number of chemical transformations that are suitable for effective protein functionalization is limited, because the stringent demands inherent to biological systems preclude the applicability of many potential processes2. These chemical transformations often need to be selective at a single site on a protein, proceed with very fast reaction rates, operate under biologically ambient conditions and should provide homogeneous products with near-perfect conversion2-7. Although many bioconjugation methods exist at cysteine, lysine and tyrosine, a method targeting a less-explored amino acid would considerably expand the protein functionalization toolbox. Here we report the development of a multifaceted approach to protein functionalization based on chemoselective labelling at methionine residues. By exploiting the electrophilic reactivity of a bespoke hypervalent iodine reagent, the S-Me group in the side chain of methionine can be targeted. The bioconjugation reaction is fast, selective, operates at low-micromolar concentrations and is complementary to existing bioconjugation strategies. Moreover, it produces a protein conjugate that is itself a high-energy intermediate with reactive properties and can serve as a platform for the development of secondary, visible-light-mediated bioorthogonal protein functionalization processes. The merger of these approaches provides a versatile platform for the development of distinct transformations that deliver information-rich protein conjugates directly from the native biomacromolecules.}, } @article {pmid30323286, year = {2018}, author = {Ortega, E and Rengachari, S and Ibrahim, Z and Hoghoughi, N and Gaucher, J and Holehouse, AS and Khochbin, S and Panne, D}, title = {Transcription factor dimerization activates the p300 acetyltransferase.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {538-544}, doi = {10.1038/s41586-018-0621-1}, pmid = {30323286}, issn = {1476-4687}, support = {16-0280//Worldwide Cancer Research/United Kingdom ; }, abstract = {The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin. Here we show that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using two model transcription factors, IRF3 and STAT1, we demonstrate that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. We describe a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighbouring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. Our data explain how cellular signalling and the activation and dimerization of transcription factors control the activation of p300, and therefore explain why gene transcription is associated with chromatin acetylation.}, } @article {pmid30323285, year = {2018}, author = {Bollong, MJ and Lee, G and Coukos, JS and Yun, H and Zambaldo, C and Chang, JW and Chin, EN and Ahmad, I and Chatterjee, AK and Lairson, LL and Schultz, PG and Moellering, RE}, title = {A metabolite-derived protein modification integrates glycolysis with KEAP1-NRF2 signalling.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {600-604}, doi = {10.1038/s41586-018-0622-0}, pmid = {30323285}, issn = {1476-4687}, support = {DP2 GM128199/GM/NIGMS NIH HHS/United States ; K99 CA175399/CA/NCI NIH HHS/United States ; R00 CA175399/CA/NCI NIH HHS/United States ; T32 GM007281/GM/NIGMS NIH HHS/United States ; }, abstract = {Mechanisms that integrate the metabolic state of a cell with regulatory pathways are necessary to maintain cellular homeostasis. Endogenous, intrinsically reactive metabolites can form functional, covalent modifications on proteins without the aid of enzymes1,2, and regulate cellular functions such as metabolism3-5 and transcription6. An important 'sensor' protein that captures specific metabolic information and transforms it into an appropriate response is KEAP1, which contains reactive cysteine residues that collectively act as an electrophile sensor tuned to respond to reactive species resulting from endogenous and xenobiotic molecules. Covalent modification of KEAP1 results in reduced ubiquitination and the accumulation of NRF27,8, which then initiates the transcription of cytoprotective genes at antioxidant-response element loci. Here we identify a small-molecule inhibitor of the glycolytic enzyme PGK1, and reveal a direct link between glycolysis and NRF2 signalling. Inhibition of PGK1 results in accumulation of the reactive metabolite methylglyoxal, which selectively modifies KEAP1 to form a methylimidazole crosslink between proximal cysteine and arginine residues (MICA). This posttranslational modification results in the dimerization of KEAP1, the accumulation of NRF2 and activation of the NRF2 transcriptional program. These results demonstrate the existence of direct inter-pathway communication between glycolysis and the KEAP1-NRF2 transcriptional axis, provide insight into the metabolic regulation of the cellular stress response, and suggest a therapeutic strategy for controlling the cytoprotective antioxidant response in several human diseases.}, } @article {pmid30323254, year = {2018}, author = {Cherrak, Y and Rapisarda, C and Pellarin, R and Bouvier, G and Bardiaux, B and Allain, F and Malosse, C and Rey, M and Chamot-Rooke, J and Cascales, E and Fronzes, R and Durand, E}, title = {Biogenesis and structure of a type VI secretion baseplate.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1404-1416}, doi = {10.1038/s41564-018-0260-1}, pmid = {30323254}, issn = {2058-5276}, abstract = {To support their growth in a competitive environment and cause pathogenesis, bacteria have evolved a broad repertoire of macromolecular machineries to deliver specific effectors and toxins. Among these multiprotein complexes, the type VI secretion system (T6SS) is a contractile nanomachine that targets both prokaryotic and eukaryotic cells. The T6SS comprises two functional subcomplexes: a bacteriophage-related tail structure anchored to the cell envelope by a membrane complex. As in other contractile injection systems, the tail is composed of an inner tube wrapped by a sheath and built on the baseplate. In the T6SS, the baseplate is not only the tail assembly platform, but also docks the tail to the membrane complex and hence serves as an evolutionary adaptor. Here we define the biogenesis pathway and report the cryo-electron microscopy (cryo-EM) structure of the wedge protein complex of the T6SS from enteroaggregative Escherichia coli (EAEC). Using an integrative approach, we unveil the molecular architecture of the whole T6SS baseplate and its interaction with the tail sheath, offering detailed insights into its biogenesis and function. We discuss architectural and mechanistic similarities but also reveal key differences with the T4 phage and Mu phage baseplates.}, } @article {pmid30323253, year = {2018}, author = {Dou, C and Xiong, J and Gu, Y and Yin, K and Wang, J and Hu, Y and Zhou, D and Fu, X and Qi, S and Zhu, X and Yao, S and Xu, H and Nie, C and Liang, Z and Yang, S and Wei, Y and Cheng, W}, title = {Structural and functional insights into the regulation of the lysis-lysogeny decision in viral communities.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1285-1294}, doi = {10.1038/s41564-018-0259-7}, pmid = {30323253}, issn = {2058-5276}, abstract = {Communication is vital for all organisms including microorganisms, which is clearly demonstrated by the bacterial quorum-sensing system. However, the molecular mechanisms underlying communication among viruses (phages) via the quorum-sensing-like 'arbitrium' system remain unclear. Viral or host densities are known to be related to an increased prevalence of lysogeny; however, how the switch from the lytic to the lysogenic pathway occurs is unknown. Thus, we sought to reveal mechanisms of communication among viruses and determine the lysogenic dynamics involved. Structural and functional analyses of the phage-derived SAIRGA and GMPRGA peptides and their corresponding receptors, phAimR and spAimR, indicated that SAIRGA directs the lysis-lysogeny decision of phi3T by modulating conformational changes in phAimR, whereas GMPRGA regulates the lysis-lysogeny pathway by stabilizing spAimR in the dimeric state. Although temperate viruses are thought to share a similar lytic-lysogenic cycle switch model, our study suggests the existence of alternative strain-specific mechanisms that regulate the lysis-lysogeny decision. Collectively, these findings provide insights into the molecular mechanisms underlying communication among viruses, offering theoretical applications for the treatment of infectious viral diseases.}, } @article {pmid30323252, year = {2018}, author = {Russ, D and Kishony, R}, title = {Additivity of inhibitory effects in multidrug combinations.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1339-1345}, doi = {10.1038/s41564-018-0252-1}, pmid = {30323252}, issn = {2058-5276}, support = {R01 GM081617/GM/NIGMS NIH HHS/United States ; }, abstract = {From natural ecology1-4 to clinical therapy5-8, cells are often exposed to mixtures of multiple drugs. Two competing null models are used to predict the combined effect of drugs: response additivity (Bliss) and dosage additivity (Loewe)9-11. Here, noting that these models diverge with increased number of drugs, we contrast their predictions with growth measurements of four phylogenetically distant microorganisms including Escherichia coli, Staphylococcus aureus, Enterococcus faecalis and Saccharomyces cerevisiae, under combinations of up to ten different drugs. In all species, as the number of drugs increases, Bliss maintains accuracy while Loewe systematically loses its predictive power. The total dosage required for growth inhibition, which Loewe predicts should be fixed, steadily increases with the number of drugs, following a square-root scaling. This scaling is explained by an approximation to Bliss where, inspired by R. A. Fisher's classical geometric model12, dosages of independent drugs add up as orthogonal vectors rather than linearly. This dose-orthogonality approximation provides results similar to Bliss, yet uses the dosage language as in Loewe and is hence easier to implement and intuit. The rejection of dosage additivity in favour of effect additivity and dosage orthogonality provides a framework for understanding how multiple drugs and stressors add up in nature and the clinic.}, } @article {pmid30323230, year = {2018}, author = {Gewin, V}, title = {Cancer researcher defends immigrant scientists.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {451}, doi = {10.1038/d41586-018-07047-z}, pmid = {30323230}, issn = {1476-4687}, } @article {pmid30323227, year = {2018}, author = {Guo, W and Gleditsch, K and Wilson, A}, title = {Retool AI to forecast and limit wars.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {331-333}, doi = {10.1038/d41586-018-07026-4}, pmid = {30323227}, issn = {1476-4687}, } @article {pmid30323226, year = {2018}, author = {Beisel, CL}, title = {CRISPR tool puts RNA on the record.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {347-349}, doi = {10.1038/d41586-018-06869-1}, pmid = {30323226}, issn = {1476-4687}, } @article {pmid30323225, year = {2018}, author = {Eme, L and Ettema, TJG}, title = {The eukaryotic ancestor shapes up.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {352-353}, doi = {10.1038/d41586-018-06868-2}, pmid = {30323225}, issn = {1476-4687}, mesh = {Actins ; *Archaea ; *Eukaryota ; Eukaryotic Cells ; Profilins ; }, } @article {pmid30323209, year = {2018}, author = {Mueller, RL and Jockusch, EL}, title = {Jumping genomic gigantism.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1687-1688}, doi = {10.1038/s41559-018-0703-3}, pmid = {30323209}, issn = {2397-334X}, } @article {pmid30323208, year = {2018}, author = {Belhabib, D and Le Billon, P}, title = {Tax havens are the tip of the iceberg.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1679}, doi = {10.1038/s41559-018-0704-2}, pmid = {30323208}, issn = {2397-334X}, } @article {pmid30323207, year = {2018}, author = {Zumberge, JA and Love, GD and Cárdenas, P and Sperling, EA and Gunasekera, S and Rohrssen, M and Grosjean, E and Grotzinger, JP and Summons, RE}, title = {Demosponge steroid biomarker 26-methylstigmastane provides evidence for Neoproterozoic animals.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1709-1714}, doi = {10.1038/s41559-018-0676-2}, pmid = {30323207}, issn = {2397-334X}, abstract = {Sterane biomarkers preserved in ancient sedimentary rocks hold promise for tracking the diversification and ecological expansion of eukaryotes. The earliest proposed animal biomarkers from demosponges (Demospongiae) are recorded in a sequence around 100 Myr long of Neoproterozoic-Cambrian marine sedimentary strata from the Huqf Supergroup, South Oman Salt Basin. This C30 sterane biomarker, informally known as 24-isopropylcholestane (24-ipc), possesses the same carbon skeleton as sterols found in some modern-day demosponges. However, this evidence is controversial because 24-ipc is not exclusive to demosponges since 24-ipc sterols are found in trace amounts in some pelagophyte algae. Here, we report a new fossil sterane biomarker that co-occurs with 24-ipc in a suite of late Neoproterozoic-Cambrian sedimentary rocks and oils, which possesses a rare hydrocarbon skeleton that is uniquely found within extant demosponge taxa. This sterane is informally designated as 26-methylstigmastane (26-mes), reflecting the very unusual methylation at the terminus of the steroid side chain. It is the first animal-specific sterane marker detected in the geological record that can be unambiguously linked to precursor sterols only reported from extant demosponges. These new findings strongly suggest that demosponges, and hence multicellular animals, were prominent in some late Neoproterozoic marine environments at least extending back to the Cryogenian period.}, } @article {pmid30323206, year = {2018}, author = {Botting, JP and Nettersheim, BJ}, title = {Searching for sponge origins.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1685-1686}, doi = {10.1038/s41559-018-0702-4}, pmid = {30323206}, issn = {2397-334X}, } @article {pmid30323177, year = {2018}, author = {Young, AI and Wauthier, FL and Donnelly, P}, title = {Identifying loci affecting trait variability and detecting interactions in genome-wide association studies.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1608-1614}, doi = {10.1038/s41588-018-0225-6}, pmid = {30323177}, issn = {1546-1718}, abstract = {Identification of genetic variants with effects on trait variability can provide insights into the biological mechanisms that control variation and can identify potential interactions. We propose a two-degree-of-freedom test for jointly testing mean and variance effects to identify such variants. We implement the test in a linear mixed model, for which we provide an efficient algorithm and software. To focus on biologically interesting settings, we develop a test for dispersion effects, that is, variance effects not driven solely by mean effects when the trait distribution is non-normal. We apply our approach to body mass index in the subsample of the UK Biobank population with British ancestry (n ~408,000) and show that our approach can increase the power to detect associated loci. We identify and replicate novel associations with significant variance effects that cannot be explained by the non-normality of body mass index, and we provide suggestive evidence for a connection between leptin levels and body mass index variability.}, } @article {pmid30322946, year = {2018}, author = {Leibovitch, EC and Caruso, B and Ha, SK and Schindler, MK and Lee, NJ and Luciano, NJ and Billioux, BJ and Guy, JR and Yen, C and Sati, P and Silva, AC and Reich, DS and Jacobson, S}, title = {Herpesvirus trigger accelerates neuroinflammation in a nonhuman primate model of multiple sclerosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11292-11297}, pmid = {30322946}, issn = {1091-6490}, mesh = {Animals ; Brain/virology ; Callithrix ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/virology ; Female ; Herpesvirus 6, Human/*pathogenicity ; Inflammation/*virology ; Male ; Multiple Sclerosis/*virology ; Primates/*virology ; Roseolovirus Infections/virology ; }, abstract = {Pathogens, particularly human herpesviruses (HHVs), are implicated as triggers of disease onset/progression in multiple sclerosis (MS) and other neuroinflammatory disorders. However, the time between viral acquisition in childhood and disease onset in adulthood complicates the study of this association. Using nonhuman primates, we demonstrate that intranasal inoculations with HHV-6A and HHV-6B accelerate an MS-like neuroinflammatory disease, experimental autoimmune encephalomyelitis (EAE). Although animals inoculated intranasally with HHV-6 (virus/EAE marmosets) were asymptomatic, they exhibited significantly accelerated clinical EAE compared with control animals. Expansion of a proinflammatory CD8 subset correlated with post-EAE survival in virus/EAE marmosets, suggesting that a peripheral (viral?) antigen-driven expansion may have occurred post-EAE induction. HHV-6 viral antigen in virus/EAE marmosets was markedly elevated and concentrated in brain lesions, similar to previously reported localizations of HHV-6 in MS brain lesions. Collectively, we demonstrate that asymptomatic intranasal viral acquisition accelerates subsequent neuroinflammation in a nonhuman primate model of MS.}, } @article {pmid30322945, year = {2018}, author = {Costa, DL and Yetter, N and DeSomer, H}, title = {Intergenerational transmission of paternal trauma among US Civil War ex-POWs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11215-11220}, pmid = {30322945}, issn = {1091-6490}, support = {P01 AG010120/AG/NIA NIH HHS/United States ; P2C HD041022/HD/NICHD NIH HHS/United States ; }, mesh = {Child ; Epigenomics/methods ; Fathers/psychology ; Female ; Humans ; Male ; Marriage/psychology ; Middle Aged ; Mothers/psychology ; Nuclear Family/psychology ; Parent-Child Relations ; Prisoners/*psychology ; Prisoners of War/*psychology ; Stress Disorders, Post-Traumatic/*etiology/genetics/*psychology ; Survivors/psychology ; Veterans/*psychology ; }, abstract = {We study whether paternal trauma is transmitted to the children of survivors of Confederate prisoner of war (POW) camps during the US Civil War (1861-1865) to affect their longevity at older ages, the mechanisms behind this transmission, and the reversibility of this transmission. We examine children born after the war who survived to age 45, comparing children whose fathers were non-POW veterans and ex-POWs imprisoned in very different camp conditions. We also compare children born before and after the war within the same family by paternal ex-POW status. The sons of ex-POWs imprisoned when camp conditions were at their worst were 1.11 times more likely to die than the sons of non-POWs and 1.09 times more likely to die than the sons of ex-POWs when camp conditions were better. Paternal ex-POW status had no impact on daughters. Among sons born in the fourth quarter, when maternal in utero nutrition was adequate, there was no impact of paternal ex-POW status. In contrast, among sons born in the second quarter, when maternal nutrition was inadequate, the sons of ex-POWs who experienced severe hardship were 1.2 times more likely to die than the sons of non-POWs and ex-POWs who fared better in captivity. Socioeconomic effects, family structure, father-specific survival traits, and maternal effects, including quality of paternal marriages, cannot explain our findings. While we cannot rule out fully psychological or cultural effects, our findings are most consistent with an epigenetic explanation.}, } @article {pmid30322944, year = {2018}, author = {Shaharabani, R and Ram-On, M and Talmon, Y and Beck, R}, title = {Pathological transitions in myelin membranes driven by environmental and multiple sclerosis conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11156-11161}, pmid = {30322944}, issn = {1091-6490}, mesh = {Cell Membrane/metabolism/*pathology ; Environment ; Humans ; Lipids/physiology ; Multiple Sclerosis/metabolism/*pathology ; Myelin Basic Protein/metabolism ; Myelin Sheath/metabolism/*pathology ; }, abstract = {Multiple sclerosis (MS) is an autoimmune disease, leading to the destruction of the myelin sheaths, the protective layers surrounding the axons. The etiology of the disease is unknown, although there are several postulated environmental factors that may contribute to it. Recently, myelin damage was correlated to structural phase transition from a healthy stack of lamellas to a diseased inverted hexagonal phase as a result of the altered lipid stoichiometry and low myelin basic protein (MBP) content. In this work, we show that environmental conditions, such as buffer salinity and temperature, induce the same pathological phase transition as in the case of the lipid composition in the absence of MBP. These phase transitions have different transition points, which depend on the lipid's compositions, and are ion specific. In extreme environmental conditions, we find an additional dense lamellar phase and that the native lipid composition results in similar pathology as the diseased composition. These findings demonstrate that several local environmental changes can trigger pathological structural changes. We postulate that these structural modifications result in myelin membrane vulnerability to the immune system attacks and thus can help explain MS etiology.}, } @article {pmid30322943, year = {2018}, author = {}, title = {Correction for Liao et al., Metal-insulator-transition engineering by modulation tilt-control in perovskite nickelates for room temperature optical switching.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10284}, doi = {10.1073/pnas.1816794115}, pmid = {30322943}, issn = {1091-6490}, } @article {pmid30322942, year = {2018}, author = {}, title = {Correction for Li et al., Mutually inhibitory Ras-PI(3,4)P2 feedback loops mediate cell migration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10286}, doi = {10.1073/pnas.1816155115}, pmid = {30322942}, issn = {1091-6490}, } @article {pmid30322941, year = {2018}, author = {Ames, BN}, title = {Prolonging healthy aging: Longevity vitamins and proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10836-10844}, pmid = {30322941}, issn = {1091-6490}, mesh = {Animals ; Avitaminosis/*diet therapy/epidemiology/*metabolism ; *Dietary Proteins ; Humans ; *Longevity ; *Models, Biological ; United States/epidemiology ; *Vitamins ; }, abstract = {It is proposed that proteins/enzymes be classified into two classes according to their essentiality for immediate survival/reproduction and their function in long-term health: that is, survival proteins versus longevity proteins. As proposed by the triage theory, a modest deficiency of one of the nutrients/cofactors triggers a built-in rationing mechanism that favors the proteins needed for immediate survival and reproduction (survival proteins) while sacrificing those needed to protect against future damage (longevity proteins). Impairment of the function of longevity proteins results in an insidious acceleration of the risk of diseases associated with aging. I also propose that nutrients required for the function of longevity proteins constitute a class of vitamins that are here named "longevity vitamins." I suggest that many such nutrients play a dual role for both survival and longevity. The evidence for classifying taurine as a conditional vitamin, and the following 10 compounds as putative longevity vitamins, is reviewed: the fungal antioxidant ergothioneine; the bacterial metabolites pyrroloquinoline quinone (PQQ) and queuine; and the plant antioxidant carotenoids lutein, zeaxanthin, lycopene, α- and β-carotene, β-cryptoxanthin, and the marine carotenoid astaxanthin. Because nutrient deficiencies are highly prevalent in the United States (and elsewhere), appropriate supplementation and/or an improved diet could reduce much of the consequent risk of chronic disease and premature aging.}, } @article {pmid30322940, year = {2018}, author = {Vogelsang, L and Gilad-Gutnick, S and Ehrenberg, E and Yonas, A and Diamond, S and Held, R and Sinha, P}, title = {Potential downside of high initial visual acuity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11333-11338}, pmid = {30322940}, issn = {1091-6490}, mesh = {Blindness/physiopathology ; Cataract/physiopathology ; Cerebral Cortex/physiology ; Facial Recognition/physiology ; Humans ; Pattern Recognition, Visual/physiology ; Photic Stimulation/methods ; Spatial Processing/physiology ; Visual Acuity/*physiology ; }, abstract = {Children who are treated for congenital cataracts later exhibit impairments in configural face analysis. This has been explained in terms of a critical period for the acquisition of normal face processing. Here, we consider a more parsimonious account according to which deficits in configural analysis result from the abnormally high initial retinal acuity that children treated for cataracts experience, relative to typical newborns. According to this proposal, the initial period of low retinal acuity characteristic of normal visual development induces extended spatial processing in the cortex that is important for configural face judgments. As a computational test of this hypothesis, we examined the effects of training with high-resolution or blurred images, and staged combinations, on the receptive fields and performance of a convolutional neural network. The results show that commencing training with blurred images creates receptive fields that integrate information across larger image areas and leads to improved performance and better generalization across a range of resolutions. These findings offer an explanation for the observed face recognition impairments after late treatment of congenital blindness, suggest an adaptive function for the acuity trajectory in normal development, and provide a scheme for improving the performance of computational face recognition systems.}, } @article {pmid30322939, year = {2018}, author = {Wada, S and Shen, B and Kawano-Yamashita, E and Nagata, T and Hibi, M and Tamotsu, S and Koyanagi, M and Terakita, A}, title = {Color opponency with a single kind of bistable opsin in the zebrafish pineal organ.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11310-11315}, pmid = {30322939}, issn = {1091-6490}, mesh = {Animals ; Color ; Color Vision/*physiology ; Fish Proteins/metabolism ; Light ; Pineal Gland/metabolism/*physiology ; Retinal Cone Photoreceptor Cells/metabolism/physiology ; Rod Opsins/metabolism/*physiology ; Ultraviolet Rays ; Zebrafish/metabolism/*physiology ; }, abstract = {Lower vertebrate pineal organs discriminate UV and visible light. Such color discrimination is typically considered to arise from antagonism between two or more spectrally distinct opsins, as, e.g., human cone-based color vision relies on antagonistic relationships between signals produced by red-, green-, and blue-cone opsins. Photosensitive pineal organs contain a bistable opsin (parapinopsin) that forms a signaling-active photoproduct upon UV exposure that may itself be returned to the signaling-inactive "dark" state by longer-wavelength light. Here we show the spectrally distinct parapinopsin states (with antagonistic impacts on signaling) allow this opsin alone to provide the color sensitivity of this organ. By using calcium imaging, we show that single zebrafish pineal photoreceptors held under a background light show responses of opposite signs to UV and visible light. Both such responses are deficient in zebrafish lacking parapinopsin. Expressing a UV-sensitive cone opsin in place of parapinopsin recovers UV responses but not color opponency. Changes in the spectral composition of white light toward enhanced UV or visible wavelengths respectively increased vs. decreased calcium signal in parapinopsin-sufficient but not parapinopsin-deficient photoreceptors. These data reveal color opponency from a single kind of bistable opsin establishing an equilibrium-like mixture of the two states with different signaling abilities whose fractional concentrations are defined by the spectral composition of incident light. As vertebrate visual color opsins evolved from a bistable opsin, these findings suggest that color opponency involving a single kind of bistable opsin might have been a prototype of vertebrate color opponency.}, } @article {pmid30322938, year = {2018}, author = {Yoon, T and Geary, RB and Ahmed, AA and Shadmehr, R}, title = {Control of movement vigor and decision making during foraging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10476-E10485}, pmid = {30322938}, issn = {1091-6490}, support = {R01 NS078311/NS/NINDS NIH HHS/United States ; R01 NS096083/NS/NINDS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *Decision Making ; Female ; Humans ; Male ; *Reaction Time ; *Saccades ; Young Adult ; }, abstract = {During foraging, animals decide how long to stay at a patch and harvest reward, and then, they move with certain vigor to another location. How does the brain decide when to leave, and how does it determine the speed of the ensuing movement? Here, we considered the possibility that both the decision-making and the motor control problems aimed to maximize a single normative utility: the sum of all rewards acquired minus all efforts expended divided by total time. This optimization could be achieved if the brain compared a local measure of utility with its history. To test the theory, we examined behavior of people as they gazed at images: they chose how long to look at the image (harvesting information) and then moved their eyes to another image, controlling saccade speed. We varied reward via image content and effort via image eccentricity, and then, we measured how these changes affected decision making (gaze duration) and motor control (saccade speed). After a history of low rewards, people increased gaze duration and decreased saccade speed. In anticipation of future effort, they lowered saccade speed and increased gaze duration. After a history of high effort, they elevated their saccade speed and increased gaze duration. Therefore, the theory presented a principled way with which the brain may control two aspects of behavior: movement speed and harvest duration. Our experiments confirmed many (but not all) of the predictions, suggesting that harvest duration and movement speed, fundamental aspects of behavior during foraging, may be governed by a shared principle of control.}, } @article {pmid30322937, year = {2018}, author = {Lowey, S and Bretton, V and Joel, PB and Trybus, KM and Gulick, J and Robbins, J and Kalganov, A and Cornachione, AS and Rassier, DE}, title = {Hypertrophic cardiomyopathy R403Q mutation in rabbit β-myosin reduces contractile function at the molecular and myofibrillar levels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11238-11243}, pmid = {30322937}, issn = {1091-6490}, support = {R21 HL111847/HL/NHLBI NIH HHS/United States ; P01 HL069779/HL/NHLBI NIH HHS/United States ; R01 AR053975/AR/NIAMS NIH HHS/United States ; R01 HL056370/HL/NHLBI NIH HHS/United States ; P01 HL110869/HL/NHLBI NIH HHS/United States ; //Canadian Institutes for Health Research/International ; }, mesh = {Actins/genetics ; Animals ; Animals, Genetically Modified/genetics ; Cardiomyopathy, Hypertrophic/*genetics ; Heart Ventricles/metabolism ; Mice ; Myocardial Contraction/*genetics ; Myocardium/metabolism ; Myofibrils/*genetics ; Myosin Heavy Chains/*genetics ; Myosins/*genetics ; Point Mutation/*genetics ; Rabbits ; }, abstract = {In 1990, the Seidmans showed that a single point mutation, R403Q, in the human β-myosin heavy chain (MHC) of heart muscle caused a particularly malignant form of familial hypertrophic cardiomyopathy (HCM) [Geisterfer-Lowrance AA, et al. (1990) Cell 62:999-1006.]. Since then, more than 300 mutations in the β-MHC have been reported, and yet there remains a poor understanding of how a single missense mutation in the MYH7 gene can lead to heart disease. Previous studies with a transgenic mouse model showed that the myosin phenotype depended on whether the mutation was in an α- or β-MHC backbone. This led to the generation of a transgenic rabbit model with the R403Q mutation in a β-MHC backbone. We find that the in vitro motility of heterodimeric R403Q myosin is markedly reduced, whereas the actin-activated ATPase activity of R403Q subfragment-1 is about the same as myosin from a nontransgenic littermate. Single myofibrils isolated from the ventricles of R403Q transgenic rabbits and analyzed by atomic force microscopy showed reduced rates of force development and relaxation, and achieved a significantly lower steady-state level of isometric force compared with nontransgenic myofibrils. Myofibrils isolated from the soleus gave similar results. The force-velocity relationship determined for R403Q ventricular myofibrils showed a decrease in the velocity of shortening under load, resulting in a diminished power output. We conclude that independent of whether experiments are performed with isolated molecules or with ordered molecules in the native thick filament of a myofibril, there is a loss-of-function induced by the R403Q mutation in β-cardiac myosin.}, } @article {pmid30322936, year = {2018}, author = {Castillo-Ruiz, A and Mosley, M and Jacobs, AJ and Hoffiz, YC and Forger, NG}, title = {Birth delivery mode alters perinatal cell death in the mouse brain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {46}, pages = {11826-11831}, pmid = {30322936}, issn = {1091-6490}, mesh = {Animals ; Brain/*embryology ; Cell Death/physiology ; Cesarean Section/*adverse effects ; Delivery, Obstetric/veterinary ; Female ; Gestational Age ; Labor, Obstetric/physiology ; Mice ; Mice, Inbred C57BL ; Paraventricular Hypothalamic Nucleus/physiology ; Parturition/*physiology ; Pregnancy ; }, abstract = {Labor and a vaginal delivery trigger changes in peripheral organs that prepare the mammalian fetus to survive ex utero. Surprisingly little attention has been given to whether birth also influences the brain, and to how alterations in birth mode affect neonatal brain development. These are important questions, given the high rates of cesarean section (C-section) delivery worldwide, many of which are elective. We examined the effect of birth mode on neuronal cell death, a widespread developmental process that occurs primarily during the first postnatal week in mice. Timed-pregnant dams were randomly assigned to C-section deliveries that were yoked to vaginal births to carefully match gestation length and circadian time of parturition. Compared with rates of cell death just before birth, vaginally-born offspring had an abrupt, transient decrease in cell death in many brain regions, suggesting that a vaginal delivery is neuroprotective. In contrast, cell death was either unchanged or increased in C-section-born mice. Effects of delivery mode on cell death were greatest for the paraventricular nucleus of the hypothalamus (PVN), which is central to the stress response and brain-immune interactions. The greater cell death in the PVN of C-section-delivered newborns was associated with a reduction in the number of PVN neurons expressing vasopressin at weaning. C-section-delivered mice also showed altered vocalizations in a maternal separation test and greater body mass at weaning. Our results suggest that vaginal birth acutely impacts brain development, and that alterations in birth mode may have lasting consequences.}, } @article {pmid30322935, year = {2018}, author = {Ma, Y and Choi, J and Hourlier-Fargette, A and Xue, Y and Chung, HU and Lee, JY and Wang, X and Xie, Z and Kang, D and Wang, H and Han, S and Kang, SK and Kang, Y and Yu, X and Slepian, MJ and Raj, MS and Model, JB and Feng, X and Ghaffari, R and Rogers, JA and Huang, Y}, title = {Relation between blood pressure and pulse wave velocity for human arteries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11144-11149}, pmid = {30322935}, issn = {1091-6490}, mesh = {Arteries/*physiology ; Blood Flow Velocity/*physiology ; Blood Pressure/*physiology ; Blood Pressure Determination/methods ; Electrocardiography/methods ; Humans ; Monitoring, Physiologic/methods ; Pulsatile Flow/*physiology ; Pulse Wave Analysis/methods ; }, abstract = {Continuous monitoring of blood pressure, an essential measure of health status, typically requires complex, costly, and invasive techniques that can expose patients to risks of complications. Continuous, cuffless, and noninvasive blood pressure monitoring methods that correlate measured pulse wave velocity (PWV) to the blood pressure via the Moens-Korteweg (MK) and Hughes Equations, offer promising alternatives. The MK Equation, however, involves two assumptions that do not hold for human arteries, and the Hughes Equation is empirical, without any theoretical basis. The results presented here establish a relation between the blood pressure P and PWV that does not rely on the Hughes Equation nor on the assumptions used in the MK Equation. This relation degenerates to the MK Equation under extremely low blood pressures, and it accurately captures the results of in vitro experiments using artificial blood vessels at comparatively high pressures. For human arteries, which are well characterized by the Fung hyperelastic model, a simple formula between P and PWV is established within the range of human blood pressures. This formula is validated by literature data as well as by experiments on human subjects, with applicability in the determination of blood pressure from PWV in continuous, cuffless, and noninvasive blood pressure monitoring systems.}, } @article {pmid30322934, year = {2018}, author = {Jin, Y and Zhou, L and Yu, J and Liang, J and Cai, W and Zhang, H and Zhu, S and Zhu, J}, title = {In operando plasmonic monitoring of electrochemical evolution of lithium metal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11168-11173}, pmid = {30322934}, issn = {1091-6490}, abstract = {The recent renaissance of lithium metal batteries as promising energy storage devices calls for in operando monitoring and control of electrochemical evolution of lithium metal morphologies. While the development of plasmonics has led to significant advancement in real-time and ultrasensitive chemical and biological sensing and surface-enhanced spectroscopies, alkali metals featured by ideal free electron gas models have long been regarded as promising plasmonic materials but seldom been explored due to their high chemical reactivity. Here, we demonstrate the in operando plasmonic monitoring of the electrochemical evolution of lithium metal during battery cycling by taking advantage of selective electrochemical deposition. The relationships between the evolving morphologies of lithium metal and in operando optical spectra are established both numerically and experimentally: Ordered growth of lithium particles shows clear size-dependent reflective dips due to hybrid surface plasmon resonances, while the formation of undesirable disordered lithium dendrites exhibits a flat spectroscopic profile with pure suppression in reflection intensity. Under the in operando plasmonic monitoring enabled by the microscopic morphology of metal, the differences of lithium evolutionary behaviors with different electrolytes can be conveniently identified without destruction. At the intersection of energy storage and plasmonics, it is expected that the ability to actively control and in operando plasmonically monitor electrochemical evolution of lithium metal can provide a promising platform for investigating lithium metal behavior during electrochemical cycling under various working conditions.}, } @article {pmid30322933, year = {2018}, author = {Shoenfelt, EM and Winckler, G and Lamy, F and Anderson, RF and Bostick, BC}, title = {Highly bioavailable dust-borne iron delivered to the Southern Ocean during glacial periods.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11180-11185}, pmid = {30322933}, issn = {1091-6490}, support = {P42 ES010349/ES/NIEHS NIH HHS/United States ; }, mesh = {Atmosphere/chemistry ; Carbon Dioxide/chemistry ; Climate ; Dust/*analysis ; Geologic Sediments/chemistry ; Ice Cover/chemistry ; Iron/*chemistry ; Minerals/chemistry ; Oceans and Seas ; Phytoplankton/*growth & development ; Seawater/chemistry ; Temperature ; }, abstract = {Changes in bioavailable dust-borne iron (Fe) supply to the iron-limited Southern Ocean may influence climate by modulating phytoplankton growth and CO2 fixation into organic matter that is exported to the deep ocean. The chemical form (speciation) of Fe impacts its bioavailability, and glacial weathering produces highly labile and bioavailable Fe minerals in modern dust sources. However, the speciation of dust-borne Fe reaching the iron-limited Southern Ocean on glacial-interglacial timescales is unknown, and its impact on the bioavailable iron supply over geologic time has not been quantified. Here we use X-ray absorption spectroscopy on subantarctic South Atlantic and South Pacific marine sediments to reconstruct dust-borne Fe speciation over the last glacial cycle, and determine the impact of glacial activity and glaciogenic dust sources on bioavailable Fe supply. We show that the Fe(II) content, as a percentage of total dust-borne Fe, increases from ∼5 to 10% in interglacial periods to ∼25 to 45% in glacial periods. Consequently, the highly bioavailable Fe(II) flux increases by a factor of ∼15 to 20 in glacial periods compared with the current interglacial, whereas the total Fe flux increases only by a factor of ∼3 to 5. The change in Fe speciation is dominated by primary Fe(II) silicates characteristic of glaciogenic dust. Our results suggest that glacial physical weathering increases the proportion of highly bioavailable Fe(II) in dust that reaches the subantarctic Southern Ocean in glacial periods, which represents a positive feedback between glacial activity and cold glacial temperatures.}, } @article {pmid30322932, year = {2018}, author = {Király, I and Oláh, K and Csibra, G and Kovács, ÁM}, title = {Retrospective attribution of false beliefs in 3-year-old children.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11477-11482}, pmid = {30322932}, issn = {1091-6490}, abstract = {A current debate in psychology and cognitive science concerns the nature of young children's ability to attribute and track others' beliefs. Beliefs can be attributed in at least two different ways: prospectively, during the observation of belief-inducing situations, and in a retrospective manner, based on episodic retrieval of the details of the events that brought about the beliefs. We developed a task in which only retrospective attribution, but not prospective belief tracking, would allow children to correctly infer that someone had a false belief. Eighteen- and 36-month-old children observed a displacement event, which was witnessed by a person wearing sunglasses (Experiment 1). Having later discovered that the sunglasses were opaque, 36-month-olds correctly inferred that the person must have formed a false belief about the location of the objects and used this inference in resolving her referential expressions. They successfully performed retrospective revision in the opposite direction as well, correcting a mistakenly attributed false belief when this was necessary (Experiment 3). Thus, children can compute beliefs retrospectively, based on episodic memories, well before they pass explicit false-belief tasks. Eighteen-month-olds failed in such a task, suggesting that they cannot retrospectively attribute beliefs or revise their initial belief attributions. However, an additional experiment provided evidence for prospective tracking of false beliefs in 18-month-olds (Experiment 2). Beyond identifying two different modes for tracking and updating others' mental states early in development, these results also provide clear evidence of episodic memory retrieval in young children.}, } @article {pmid30322931, year = {2018}, author = {Shukla, SP and Plata, C and Reichelt, M and Steiger, S and Heckel, DG and Kaltenpoth, M and Vilcinskas, A and Vogel, H}, title = {Microbiome-assisted carrion preservation aids larval development in a burying beetle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11274-11279}, pmid = {30322931}, issn = {1091-6490}, mesh = {Animals ; Bacteria/metabolism ; Biofilms/growth & development ; Cadaverine/metabolism ; Coleoptera/*growth & development/*microbiology ; Fungi/metabolism ; Larva/*growth & development/*microbiology ; Microbiota/*physiology ; Putrescine/metabolism ; Transcriptome/genetics ; }, abstract = {The ability to feed on a wide range of diets has enabled insects to diversify and colonize specialized niches. Carrion, for example, is highly susceptible to microbial decomposers, but is kept palatable several days after an animal's death by carrion-feeding insects. Here we show that the burying beetle Nicrophorus vespilloides preserves carrion by preventing the microbial succession associated with carrion decomposition, thus ensuring a high-quality resource for their developing larvae. Beetle-tended carcasses showed no signs of degradation and hosted a microbial community containing the beetles' gut microbiota, including the yeast Yarrowia In contrast, untended carcasses showed visual and olfactory signs of putrefaction, and their microbial community consisted of endogenous and soil-originating microbial decomposers. This regulation of the carcass' bacterial and fungal community and transcriptomic profile was associated with lower concentrations of putrescine and cadaverine (toxic polyamines associated with carcass putrefaction) and altered levels of proteases, lipases, and free amino acids. Beetle-tended carcasses develop a biofilm-like matrix housing the yeast, which, when experimentally removed, leads to reduced larval growth. Thus, tended carcasses hosted a mutualistic microbial community that promotes optimal larval development, likely through symbiont-mediated extraintestinal digestion and detoxification of carrion nutrients. The adaptive preservation of carrion coordinated by the beetles and their symbionts demonstrates a specialized resource-management strategy through which insects modify their habitats to enhance fitness.}, } @article {pmid30322930, year = {2018}, author = {Yang, B and Wu, H and Schnier, PD and Liu, Y and Liu, J and Wang, N and DeGrado, WF and Wang, L}, title = {Proximity-enhanced SuFEx chemical cross-linker for specific and multitargeting cross-linking mass spectrometry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11162-11167}, pmid = {30322930}, issn = {1091-6490}, support = {P01 AG002132/AG/NIA NIH HHS/United States ; RF1 MH114079/MH/NIMH NIH HHS/United States ; TL1 TR001871/TR/NCATS NIH HHS/United States ; R35 GM122603/GM/NIGMS NIH HHS/United States ; R01 GM118384/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acids/chemistry ; Cross-Linking Reagents/*chemistry ; Escherichia coli/metabolism ; Fluorides/*chemistry ; Lysine/chemistry ; Mass Spectrometry/methods ; Proteins/chemistry ; Succinimides/chemistry ; Sulfur Compounds/*chemistry ; }, abstract = {Chemical cross-linking mass spectrometry (CXMS) is being increasingly used to study protein assemblies and complex protein interaction networks. Existing CXMS chemical cross-linkers target only Lys, Cys, Glu, and Asp residues, limiting the information measurable. Here we report a "plant-and-cast" cross-linking strategy that employs a heterobifunctional cross-linker that contains a highly reactive succinimide ester as well as a less reactive sulfonyl fluoride. The succinimide ester reacts rapidly with surface Lys residues "planting" the reagent at fixed locations on protein. The pendant aryl sulfonyl fluoride is then "cast" across a limited range of the protein surface, where it can react with multiple weakly nucleophilic amino acid sidechains in a proximity-enhanced sulfur-fluoride exchange (SuFEx) reaction. Using proteins of known structures, we demonstrated that the heterobifunctional agent formed cross-links between Lys residues and His, Ser, Thr, Tyr, and Lys sidechains. This geometric specificity contrasts with current bis-succinimide esters, which often generate nonspecific cross-links between lysines brought into proximity by rare thermal fluctuations. Thus, the current method can provide diverse and robust distance restraints to guide integrative modeling. This work provides a chemical cross-linker targeting unactivated Ser, Thr, His, and Tyr residues using sulfonyl fluorides. In addition, this methodology yielded a variety of cross-links when applied to the complex Escherichia coli cell lysate. Finally, in combination with genetically encoded chemical cross-linking, cross-linking using this reagent markedly increased the identification of weak and transient enzyme-substrate interactions in live cells. Proximity-dependent cross-linking will dramatically expand the scope and power of CXMS for defining the identities and structures of protein complexes.}, } @article {pmid30322929, year = {2018}, author = {Paerl, RW and Sundh, J and Tan, D and Svenningsen, SL and Hylander, S and Pinhassi, J and Andersson, AF and Riemann, L}, title = {Prevalent reliance of bacterioplankton on exogenous vitamin B1 and precursor availability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10447-E10456}, pmid = {30322929}, issn = {1091-6490}, mesh = {Bacteria/genetics/*metabolism ; Fresh Water ; Gene Expression Regulation, Bacterial ; Genome, Bacterial ; Genomics/*methods ; Genotype ; Plankton ; Seawater ; Thiamine/*metabolism ; Transcriptome ; }, abstract = {Vitamin B1 (B1 herein) is a vital enzyme cofactor required by virtually all cells, including bacterioplankton, which strongly influence aquatic biogeochemistry and productivity and modulate climate on Earth. Intriguingly, bacterioplankton can be de novo B1 synthesizers or B1 auxotrophs, which cannot synthesize B1 de novo and require exogenous B1 or B1 precursors to survive. Recent isolate-based work suggests select abundant bacterioplankton are B1 auxotrophs, but direct evidence of B1 auxotrophy among natural communities is scant. In addition, it is entirely unknown if bulk bacterioplankton growth is ever B1-limited. We show by surveying for B1-related genes in estuarine, marine, and freshwater metagenomes and metagenome-assembled genomes (MAGs) that most naturally occurring bacterioplankton are B1 auxotrophs. Pyrimidine B1-auxotrophic bacterioplankton numerically dominated metagenomes, but multiple other B1-auxotrophic types and distinct uptake and B1-salvaging strategies were also identified, including dual (pyrimidine and thiazole) and intact B1 auxotrophs that have received little prior consideration. Time-series metagenomes from the Baltic Sea revealed pronounced shifts in the prevalence of multiple B1-auxotrophic types and in the B1-uptake and B1-salvaging strategies over time. Complementarily, we documented B1/precursor limitation of bacterioplankton production in three of five nutrient-amendment experiments at the same time-series station, specifically when intact B1 concentrations were ≤3.7 pM, based on bioassays with a genetically engineered Vibrio anguillarum B1-auxotrophic strain. Collectively, the data presented highlight the prevalent reliance of bacterioplankton on exogenous B1/precursors and on the bioavailability of the micronutrients as an overlooked factor that could influence bacterioplankton growth and succession and thereby the cycling of nutrients and energy in aquatic systems.}, } @article {pmid30322928, year = {2018}, author = {Arora, H and Panara, K and Kuchakulla, M and Kulandavelu, S and Burnstein, KL and Schally, AV and Hare, JM and Ramasamy, R}, title = {Alterations of tumor microenvironment by nitric oxide impedes castration-resistant prostate cancer growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11298-11303}, pmid = {30322928}, issn = {1091-6490}, support = {R01 HL107110/HL/NHLBI NIH HHS/United States ; UM1 HL113460/HL/NHLBI NIH HHS/United States ; R01 CA136387/CA/NCI NIH HHS/United States ; R01 HL137355/HL/NHLBI NIH HHS/United States ; R01 HL134558/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/physiology ; Cell Line, Tumor ; Cell Proliferation/*physiology ; Gene Expression Regulation, Neoplastic/physiology ; Inflammation/metabolism/pathology ; MAP Kinase Signaling System/physiology ; Macrophages/metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Nitric Oxide/*metabolism ; Nitric Oxide Donors/metabolism ; Prostatic Neoplasms, Castration-Resistant/*metabolism/*pathology ; Tumor Burden/physiology ; Tumor Microenvironment/*physiology ; Xenograft Model Antitumor Assays/methods ; }, abstract = {Immune targeted therapy of nitric oxide (NO) synthases are being considered as a potential frontline therapeutic to treat patients diagnosed with locally advanced and metastatic prostate cancer. However, the role of NO in castration-resistant prostate cancer (CRPC) is controversial because NO can increase in nitrosative stress while simultaneously possessing antiinflammatory properties. Accordingly, we tested the hypothesis that increased NO will lead to tumor suppression of CRPC through tumor microenvironment. S-nitrosoglutathione (GSNO), an NO donor, decreased the tumor burden in murine model of CRPC by targeting tumors in a cell nonautonomous manner. GSNO inhibited both the abundance of antiinflammatory (M2) macrophages and expression of pERK, indicating that tumor-associated macrophages activity is influenced by NO. Additionally, GSNO decreased IL-34, indicating suppression of tumor-associated macrophage differentiation. Cytokine profiling of CRPC tumor grafts exposed to GSNO revealed a significant decrease in expression of G-CSF and M-CSF compared with grafts not exposed to GSNO. We verified the durability of NO on CRPC tumor suppression by using secondary xenograft murine models. This study validates the significance of NO on inhibition of CRPC tumors through tumor microenvironment (TME). These findings may facilitate the development of previously unidentified NO-based therapy for CRPC.}, } @article {pmid30322927, year = {2018}, author = {Jenson, JM and Xue, V and Stretz, L and Mandal, T and Reich, LL and Keating, AE}, title = {Peptide design by optimization on a data-parameterized protein interaction landscape.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10342-E10351}, pmid = {30322927}, issn = {1091-6490}, support = {P30 GM124165/GM/NIGMS NIH HHS/United States ; R01 GM096466/GM/NIGMS NIH HHS/United States ; R01 GM110048/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Apoptosis Regulatory Proteins/metabolism ; Cell Line ; Escherichia coli/metabolism ; Humans ; Mice ; Myeloid Cell Leukemia Sequence 1 Protein/metabolism ; Peptides/*chemistry/*metabolism ; Protein Binding/physiology ; Protein Engineering/methods ; Proto-Oncogene Proteins c-bcl-2/metabolism ; Yeasts/metabolism ; bcl-X Protein/metabolism ; }, abstract = {Many applications in protein engineering require optimizing multiple protein properties simultaneously, such as binding one target but not others or binding a target while maintaining stability. Such multistate design problems require navigating a high-dimensional space to find proteins with desired characteristics. A model that relates protein sequence to functional attributes can guide design to solutions that would be hard to discover via screening. In this work, we measured thousands of protein-peptide binding affinities with the high-throughput interaction assay amped SORTCERY and used the data to parameterize a model of the alpha-helical peptide-binding landscape for three members of the Bcl-2 family of proteins: Bcl-xL, Mcl-1, and Bfl-1. We applied optimization protocols to explore extremes in this landscape to discover peptides with desired interaction profiles. Computational design generated 36 peptides, all of which bound with high affinity and specificity to just one of Bcl-xL, Mcl-1, or Bfl-1, as intended. We designed additional peptides that bound selectively to two out of three of these proteins. The designed peptides were dissimilar to known Bcl-2-binding peptides, and high-resolution crystal structures confirmed that they engaged their targets as expected. Excellent results on this challenging problem demonstrate the power of a landscape modeling approach, and the designed peptides have potential uses as diagnostic tools or cancer therapeutics.}, } @article {pmid30322926, year = {2018}, author = {}, title = {Correction for Kneller, Franck-Condon picture of incoherent neutron scattering.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10283}, doi = {10.1073/pnas.1816793115}, pmid = {30322926}, issn = {1091-6490}, } @article {pmid30322925, year = {2018}, author = {Kellner, JR and Hubbell, SP}, title = {Density-dependent adult recruitment in a low-density tropical tree.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11268-11273}, pmid = {30322925}, issn = {1091-6490}, mesh = {Bayes Theorem ; Ecosystem ; Forests ; Panama ; Population Density ; Population Dynamics ; Seedlings/growth & development ; Seeds/growth & development ; Tabebuia/*growth & development ; Tropical Climate ; }, abstract = {The Janzen-Connell hypothesis is a well-known explanation for why tropical forests have large numbers of tree species. A fundamental prediction of the hypothesis is that the probability of adult recruitment is less in regions of high conspecific adult density, a pattern mediated by density-dependent mortality in juvenile life stages. Although there is strong evidence in many tree species that seeds, seedlings, and saplings suffer conspecific density-dependent mortality, no study has shown that adult tree recruitment is negatively density dependent. Density-dependent adult recruitment is necessary for the Janzen-Connell mechanism to regulate tree populations. Here, we report density-dependent adult recruitment in the population of Handroanthus guayacan, a wind-dispersed Neotropical canopy tree species. We use data from high-resolution remote sensing to track individual trees with proven capacity to flower in a lowland moist forest landscape in Panama and analyze these data in a Bayesian framework similar to capture-recapture analysis. We independently quantify probabilities of adult tree recruitment and detection and show that adult recruitment is negatively density dependent. The annualized probability of adult recruitment was 3.03% ⋅ year-1 Despite the detection of negative density dependence in adult recruitment, it was insufficient to stabilize the adult population of H. guayacan, which increased significantly in size over the decade of observation.}, } @article {pmid30322924, year = {2018}, author = {Davis, M and Faurby, S and Svenning, JC}, title = {Mammal diversity will take millions of years to recover from the current biodiversity crisis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11262-11267}, pmid = {30322924}, issn = {1091-6490}, mesh = {Animals ; Biodiversity ; Biological Evolution ; Extinction, Biological ; Humans ; Mammals/*classification/genetics ; Phylogeny ; }, abstract = {The incipient sixth mass extinction that started in the Late Pleistocene has already erased over 300 mammal species and, with them, more than 2.5 billion y of unique evolutionary history. At the global scale, this lost phylogenetic diversity (PD) can only be restored with time as lineages evolve and create new evolutionary history. Given the increasing rate of extinctions however, can mammals evolve fast enough to recover their lost PD on a human time scale? We use a birth-death tree framework to show that even if extinction rates slow to preanthropogenic background levels, recovery of lost PD will likely take millions of years. These findings emphasize the severity of the potential sixth mass extinction and the need to avoid the loss of unique evolutionary history now.}, } @article {pmid30322923, year = {2018}, author = {Newton, K and Dugger, DL and Sengupta-Ghosh, A and Ferrando, RE and Chu, F and Tao, J and Lam, W and Haller, S and Chan, S and Sa, S and Dunlap, D and Eastham-Anderson, J and Ngu, H and Hung, J and French, DM and Webster, JD and Bolon, B and Liu, J and Reja, R and Kummerfeld, S and Chen, YJ and Modrusan, Z and Lewcock, JW and Dixit, VM}, title = {Ubiquitin ligase COP1 coordinates transcriptional programs that control cell type specification in the developing mouse brain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11244-11249}, pmid = {30322923}, issn = {1091-6490}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Brain/*metabolism ; DNA-Binding Proteins/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/*metabolism ; Proto-Oncogene Proteins c-ets/metabolism ; Proto-Oncogene Proteins c-jun/metabolism ; Transcription Factors/metabolism ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligases/*metabolism ; }, abstract = {The E3 ubiquitin ligase CRL4COP1/DET1 is active in the absence of ERK signaling, modifying the transcription factors ETV1, ETV4, ETV5, and c-JUN with polyubiquitin that targets them for proteasomal degradation. Here we show that this posttranslational regulatory mechanism is active in neurons, with ETV5 and c-JUN accumulating within minutes of ERK activation. Mice with constitutive photomorphogenesis 1 (Cop1) deleted in neural stem cells showed abnormally elevated expression of ETV1, ETV4, ETV5, and c-JUN in the developing brain and spinal cord. Expression of c-JUN target genes Vimentin and Gfap was increased, whereas ETV5 and c-JUN both contributed to an expanded number of cells expressing genes associated with gliogenesis, including Olig1, Olig2, and Sox10. The mice had subtle morphological abnormalities in the cerebral cortex, hippocampus, and cerebellum by embryonic day 18 and died soon after birth. Elevated c-JUN, ETV5, and ETV1 contributed to the perinatal lethality, as several Cop1-deficient mice also lacking c-Jun and Etv5, or lacking Etv5 and heterozygous for Etv1, were viable.}, } @article {pmid30322922, year = {2018}, author = {Lister, BC and Garcia, A}, title = {Climate-driven declines in arthropod abundance restructure a rainforest food web.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10397-E10406}, pmid = {30322922}, issn = {1091-6490}, mesh = {Animals ; Arthropods/*growth & development ; Biodiversity ; Biomass ; Birds/growth & development ; Ecosystem ; El Nino-Southern Oscillation/adverse effects ; Food Chain ; Forests ; Puerto Rico ; Rainforest ; Trees/growth & development ; Tropical Climate/*adverse effects ; }, abstract = {A number of studies indicate that tropical arthropods should be particularly vulnerable to climate warming. If these predictions are realized, climate warming may have a more profound impact on the functioning and diversity of tropical forests than currently anticipated. Although arthropods comprise over two-thirds of terrestrial species, information on their abundance and extinction rates in tropical habitats is severely limited. Here we analyze data on arthropod and insectivore abundances taken between 1976 and 2012 at two midelevation habitats in Puerto Rico's Luquillo rainforest. During this time, mean maximum temperatures have risen by 2.0 °C. Using the same study area and methods employed by Lister in the 1970s, we discovered that the dry weight biomass of arthropods captured in sweep samples had declined 4 to 8 times, and 30 to 60 times in sticky traps. Analysis of long-term data on canopy arthropods and walking sticks taken as part of the Luquillo Long-Term Ecological Research program revealed sustained declines in abundance over two decades, as well as negative regressions of abundance on mean maximum temperatures. We also document parallel decreases in Luquillo's insectivorous lizards, frogs, and birds. While El Niño/Southern Oscillation influences the abundance of forest arthropods, climate warming is the major driver of reductions in arthropod abundance, indirectly precipitating a bottom-up trophic cascade and consequent collapse of the forest food web.}, } @article {pmid30322921, year = {2018}, author = {Bajić, D and Vila, JCC and Blount, ZD and Sánchez, A}, title = {On the deformability of an empirical fitness landscape by microbial evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11286-11291}, pmid = {30322921}, issn = {1091-6490}, mesh = {Escherichia coli/*genetics ; Evolution, Molecular ; Genetic Fitness/*genetics ; Genotype ; Models, Genetic ; Mutation/genetics ; }, abstract = {A fitness landscape is a map between the genotype and its reproductive success in a given environment. The topography of fitness landscapes largely governs adaptive dynamics, constraining evolutionary trajectories and the predictability of evolution. Theory suggests that this topography can be deformed by mutations that produce substantial changes to the environment. Despite its importance, the deformability of fitness landscapes has not been systematically studied beyond abstract models, and little is known about its reach and consequences in empirical systems. Here we have systematically characterized the deformability of the genome-wide metabolic fitness landscape of the bacterium Escherichia coli Deformability is quantified by the noncommutativity of epistatic interactions, which we experimentally demonstrate in mutant strains on the path to an evolutionary innovation. Our analysis shows that the deformation of fitness landscapes by metabolic mutations rarely affects evolutionary trajectories in the short range. However, mutations with large environmental effects produce long-range landscape deformations in distant regions of the genotype space that affect the fitness of later descendants. Our results therefore suggest that, even in situations in which mutations have strong environmental effects, fitness landscapes may retain their power to forecast evolution over small mutational distances despite the potential attenuation of that power over longer evolutionary trajectories. Our methods and results provide an avenue for integrating adaptive and eco-evolutionary dynamics with complex genetics and genomics.}, } @article {pmid30322920, year = {2018}, author = {Marie, R and Pedersen, JN and Bærlocher, L and Koprowska, K and Pødenphant, M and Sabatel, C and Zalkovskij, M and Mironov, A and Bilenberg, B and Ashley, N and Flyvbjerg, H and Bodmer, WF and Kristensen, A and Mir, KU}, title = {Single-molecule DNA-mapping and whole-genome sequencing of individual cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11192-11197}, pmid = {30322920}, issn = {1091-6490}, mesh = {Cell Line, Tumor ; Chromosome Mapping/*methods ; Chromosomes, Human, Pair 19/genetics ; Chromosomes, Human, Pair 4/genetics ; Clonal Evolution/genetics ; Colorectal Neoplasms/genetics ; DNA/*genetics ; Genome/*genetics ; Genomics/methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/*methods ; Sequence Deletion/genetics ; }, abstract = {To elucidate cellular diversity and clonal evolution in tissues and tumors, one must resolve genomic heterogeneity in single cells. To this end, we have developed low-cost, mass-producible micro-/nanofluidic chips for DNA extraction from individual cells. These chips have modules that collect genomic DNA for sequencing or map genomic structure directly, on-chip, with denaturation-renaturation (D-R) optical mapping [Marie R, et al. (2013) Proc Natl Acad Sci USA 110:4893-4898]. Processing of single cells from the LS174T colorectal cancer cell line showed that D-R mapping of single molecules can reveal structural variation (SV) in the genome of single cells. In one experiment, we processed 17 fragments covering 19.8 Mb of the cell's genome. One megabase-large fragment aligned well to chromosome 19 with half its length, while the other half showed variable alignment. Paired-end single-cell sequencing supported this finding, revealing a region of complexity and a 50-kb deletion. Sequencing struggled, however, to detect a 20-kb gap that D-R mapping showed clearly in a megabase fragment that otherwise mapped well to the reference at the pericentromeric region of chromosome 4. Pericentromeric regions are complex and show substantial sequence homology between different chromosomes, making mapping of sequence reads ambiguous. Thus, D-R mapping directly, from a single molecule, revealed characteristics of the single-cell genome that were challenging for short-read sequencing.}, } @article {pmid30322919, year = {2018}, author = {Knöll, J and Pillow, JW and Huk, AC}, title = {Lawful tracking of visual motion in humans, macaques, and marmosets in a naturalistic, continuous, and untrained behavioral context.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10486-E10494}, pmid = {30322919}, issn = {1091-6490}, support = {R01 EY017366/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Callithrix/*physiology ; Eye Movements/*physiology ; Humans ; Macaca mulatta/*physiology ; Male ; Motion Perception/*physiology ; Photic Stimulation/methods ; Young Adult ; }, abstract = {Much study of the visual system has focused on how humans and monkeys integrate moving stimuli over space and time. Such assessments of spatiotemporal integration provide fundamental grounding for the interpretation of neurophysiological data, as well as how the resulting neural signals support perceptual decisions and behavior. However, the insights supported by classical characterizations of integration performed in humans and rhesus monkeys are potentially limited with respect to both generality and detail: Standard tasks require extensive amounts of training, involve abstract stimulus-response mappings, and depend on combining data across many trials and/or sessions. It is thus of concern that the integration observed in classical tasks involves the recruitment of brain circuits that might not normally subsume natural behaviors, and that quantitative analyses have limited power for characterizing single-trial or single-session processes. Here we bridge these gaps by showing that three primate species (humans, macaques, and marmosets) track the focus of expansion of an optic flow field continuously and without substantial training. This flow-tracking behavior was volitional and reflected substantial temporal integration. Most strikingly, gaze patterns exhibited lawful and nuanced dependencies on random perturbations in the stimulus, such that repetitions of identical flow movies elicited remarkably similar eye movements over long and continuous time periods. These results demonstrate the generality of spatiotemporal integration in natural vision, and offer a means for studying integration outside of artificial tasks while maintaining lawful and highly reliable behavior.}, } @article {pmid30322918, year = {2018}, author = {Good, BH and Martis, S and Hallatschek, O}, title = {Adaptation limits ecological diversification and promotes ecological tinkering during the competition for substitutable resources.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10407-E10416}, pmid = {30322918}, issn = {1091-6490}, support = {R01 GM115851/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*physiology ; Ecology/methods ; Ecosystem ; Ecotype ; Models, Biological ; Phenotype ; Population Dynamics ; Selection, Genetic/genetics ; }, abstract = {Microbial communities can evade competitive exclusion by diversifying into distinct ecological niches. This spontaneous diversification often occurs amid a backdrop of directional selection on other microbial traits, where competitive exclusion would normally apply. Yet despite their empirical relevance, little is known about how diversification and directional selection combine to determine the ecological and evolutionary dynamics within a community. To address this gap, we introduce a simple, empirically motivated model of eco-evolutionary feedback based on the competition for substitutable resources. Individuals acquire heritable mutations that alter resource uptake rates, either by shifting metabolic effort between resources or by increasing the overall growth rate. While these constitutively beneficial mutations are trivially favored to invade, we show that the accumulated fitness differences can dramatically influence the ecological structure and evolutionary dynamics that emerge within the community. Competition between ecological diversification and ongoing fitness evolution leads to a state of diversification-selection balance, in which the number of extant ecotypes can be pinned below the maximum capacity of the ecosystem, while the ecotype frequencies and genealogies are constantly in flux. Interestingly, we find that fitness differences generate emergent selection pressures to shift metabolic effort toward resources with lower effective competition, even in saturated ecosystems. We argue that similar dynamical features should emerge in a wide range of models with a mixture of directional and diversifying selection.}, } @article {pmid30322917, year = {2018}, author = {Mann, RP}, title = {Collective decision making by rational individuals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10387-E10396}, pmid = {30322917}, issn = {1091-6490}, mesh = {Animals ; Data Collection/methods ; Decision Making/*physiology ; Decision Theory ; Humans ; Interpersonal Relations ; Social Behavior ; }, abstract = {The patterns and mechanisms of collective decision making in humans and animals have attracted both empirical and theoretical attention. Of particular interest has been the variety of social feedback rules and the extent to which these behavioral rules can be explained and predicted from theories of rational estimation and decision making. However, models that aim to model the full range of social information use have incorporated ad hoc departures from rational decision-making theory to explain the apparent stochasticity and variability of behavior. In this paper I develop a model of social information use and collective decision making by fully rational agents that reveals how a wide range of apparently stochastic social decision rules emerge from fundamental information asymmetries both between individuals and between the decision makers and the observer of those decisions. As well as showing that rational decision making is consistent with empirical observations of collective behavior, this model makes several testable predictions about how individuals make decisions in groups and offers a valuable perspective on how we view sources of variability in animal, and human, behavior.}, } @article {pmid30322916, year = {2018}, author = {Flesch, T and Balaguer, J and Dekker, R and Nili, H and Summerfield, C}, title = {Comparing continual task learning in minds and machines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10313-E10322}, pmid = {30322916}, issn = {1091-6490}, mesh = {Adult ; Algorithms ; Artificial Intelligence ; Computer Simulation ; Female ; Humans ; Learning/*physiology ; Machine Learning ; Male ; Middle Aged ; Nerve Net/*physiology ; Neural Networks (Computer) ; Task Performance and Analysis ; Young Adult ; }, abstract = {Humans can learn to perform multiple tasks in succession over the lifespan ("continual" learning), whereas current machine learning systems fail. Here, we investigated the cognitive mechanisms that permit successful continual learning in humans and harnessed our behavioral findings for neural network design. Humans categorized naturalistic images of trees according to one of two orthogonal task rules that were learned by trial and error. Training regimes that focused on individual rules for prolonged periods (blocked training) improved human performance on a later test involving randomly interleaved rules, compared with control regimes that trained in an interleaved fashion. Analysis of human error patterns suggested that blocked training encouraged humans to form "factorized" representation that optimally segregated the tasks, especially for those individuals with a strong prior bias to represent the stimulus space in a well-structured way. By contrast, standard supervised deep neural networks trained on the same tasks suffered catastrophic forgetting under blocked training, due to representational interference in the deeper layers. However, augmenting deep networks with an unsupervised generative model that allowed it to first learn a good embedding of the stimulus space (similar to that observed in humans) reduced catastrophic forgetting under blocked training. Building artificial agents that first learn a model of the world may be one promising route to solving continual task performance in artificial intelligence research.}, } @article {pmid30322915, year = {2018}, author = {Fei, DL and Zhen, T and Durham, B and Ferrarone, J and Zhang, T and Garrett, L and Yoshimi, A and Abdel-Wahab, O and Bradley, RK and Liu, P and Varmus, H}, title = {Impaired hematopoiesis and leukemia development in mice with a conditional knock-in allele of a mutant splicing factor gene U2af1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10437-E10446}, pmid = {30322915}, issn = {1091-6490}, mesh = {Alleles ; Animals ; Core Binding Factor Alpha 2 Subunit/genetics/metabolism ; Ethylnitrosourea/toxicity ; Gene Expression Regulation/drug effects ; Genetic Predisposition to Disease ; Genotype ; Hematopoiesis/*genetics ; Humans ; Leukemia/*genetics ; Mice ; Mice, Transgenic ; Mutation ; Myelodysplastic Syndromes/genetics ; RNA Splicing ; Splicing Factor U2AF/genetics/*metabolism ; }, abstract = {Mutations affecting the spliceosomal protein U2AF1 are commonly found in myelodysplastic syndromes (MDS) and secondary acute myeloid leukemia (sAML). We have generated mice that carry Cre-dependent knock-in alleles of U2af1(S34F), the murine version of the most common mutant allele of U2AF1 encountered in human cancers. Cre-mediated recombination in murine hematopoietic lineages caused changes in RNA splicing, as well as multilineage cytopenia, macrocytic anemia, decreased hematopoietic stem and progenitor cells, low-grade dysplasias, and impaired transplantability, but without lifespan shortening or leukemia development. In an attempt to identify U2af1(S34F)-cooperating changes that promote leukemogenesis, we combined U2af1(S34F) with Runx1 deficiency in mice and further treated the mice with a mutagen, N-ethyl-N-nitrosourea (ENU). Overall, 3 of 16 ENU-treated compound transgenic mice developed AML. However, AML did not arise in mice with other genotypes or without ENU treatment. Sequencing DNA from the three AMLs revealed somatic mutations homologous to those considered to be drivers of human AML, including predicted loss- or gain-of-function mutations in Tet2, Gata2, Idh1, and Ikzf1 However, the engineered U2af1(S34F) missense mutation reverted to WT in two of the three AML cases, implying that U2af1(S34F) is dispensable, or even selected against, once leukemia is established.}, } @article {pmid30322914, year = {2018}, author = {Wang, Z and Okada, Y and O'Neal, J and Zhou, W and Walkup, D and Dhital, C and Hogan, T and Clancy, P and Kim, YJ and Hu, YF and Santos, LH and Wilson, SD and Trivedi, N and Madhavan, V}, title = {Disorder induced power-law gaps in an insulator-metal Mott transition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11198-11202}, pmid = {30322914}, issn = {1091-6490}, support = {//Canadian Institutes of Health Research/International ; }, abstract = {A correlated material in the vicinity of an insulator-metal transition (IMT) exhibits rich phenomenology and a variety of interesting phases. A common avenue to induce IMTs in Mott insulators is doping, which inevitably leads to disorder. While disorder is well known to create electronic inhomogeneity, recent theoretical studies have indicated that it may play an unexpected and much more profound role in controlling the properties of Mott systems. Theory predicts that disorder might play a role in driving a Mott insulator across an IMT, with the emergent metallic state hosting a power-law suppression of the density of states (with exponent close to 1; V-shaped gap) centered at the Fermi energy. Such V-shaped gaps have been observed in Mott systems, but their origins are as-yet unknown. To investigate this, we use scanning tunneling microscopy and spectroscopy to study isovalent Ru substitutions in Sr3(Ir1-xRux)2O7 (0 ≤ x ≤ 0.5) which drive the system into an antiferromagnetic, metallic state. Our experiments reveal that many core features of the IMT, such as power-law density of states, pinning of the Fermi energy with increasing disorder, and persistence of antiferromagnetism, can be understood as universal features of a disordered Mott system near an IMT and suggest that V-shaped gaps may be an inevitable consequence of disorder in doped Mott insulators.}, } @article {pmid30322913, year = {2018}, author = {Branciamore, S and Valo, Z and Li, M and Wang, J and Riggs, AD and Singer-Sam, J}, title = {Frequent monoallelic or skewed expression for developmental genes in CNS-derived cells and evidence for balancing selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10379-E10386}, pmid = {30322913}, issn = {1091-6490}, mesh = {Alleles ; Animals ; Astrocytes/physiology ; Cell Differentiation/genetics ; Central Nervous System/*physiology ; Female ; Gene Expression Regulation, Developmental/*genetics ; Genes, Developmental/*genetics ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/physiology ; Promoter Regions, Genetic/genetics ; Selection, Genetic/*genetics ; }, abstract = {Cellular mosaicism due to monoallelic autosomal expression (MAE), with cell selection during development, is becoming increasingly recognized as prevalent in mammals, leading to interest in understanding its extent and mechanism(s). We report here use of clonal cell lines derived from the CNS of adult female [Formula: see text] hybrid (C57BL/6 X JF1) mice to characterize MAE as neural stem cells (nscs) differentiate to astrocyte-like cells (asls). We found that different subsets of genes show MAE in the two populations of cells; in each case, there is strong enrichment for genes specific to the respective developmental state. Genes that exhibit MAE are 22% of nsc-specific genes and 26% of asl-specific genes. Moreover, the promoters of genes with MAE have reduced CpG dinucleotides but increased CpG differences between the two parental mouse strains. Extending the study of variability to wild populations of mice, we found evidence for balancing selection as a contributing force in evolution of those genes showing developmental specificity (i.e., expressed in either nsc or asl), not just for genes showing MAE. Furthermore, we found that genes showing skewed allelic expression (SKE) were similarly enriched among cell type-specific genes and also showed a heightened probability of balancing selection. Thus, developmental stage-specific genes and genes with MAE or SKE seem to make up overlapping classes subject to selection for increased diversity. The implications of these results for development and evolution are discussed in the context of a model with stochastic epigenetic modifications taking place only during a relatively brief developmental window.}, } @article {pmid30322912, year = {2018}, author = {}, title = {Correction for Baldwin and Mussweiler, The culture of social comparison.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10285}, doi = {10.1073/pnas.1816586115}, pmid = {30322912}, issn = {1091-6490}, } @article {pmid30322911, year = {2018}, author = {Abraham, R and Hauer, D and McPherson, RL and Utt, A and Kirby, IT and Cohen, MS and Merits, A and Leung, AKL and Griffin, DE}, title = {ADP-ribosyl-binding and hydrolase activities of the alphavirus nsP3 macrodomain are critical for initiation of virus replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10457-E10466}, pmid = {30322911}, issn = {1091-6490}, support = {R01 GM104135/GM/NIGMS NIH HHS/United States ; T32 CA009110/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Chikungunya virus/*genetics ; Gene Expression Regulation, Viral/*physiology ; Mutation ; Neurons/virology ; Protein Domains ; RNA, Viral ; Viral Nonstructural Proteins/genetics/*metabolism ; Viral Proteins/metabolism ; Virus Replication/*physiology ; }, abstract = {Alphaviruses are plus-strand RNA viruses that cause encephalitis, rash, and arthritis. The nonstructural protein (nsP) precursor polyprotein is translated from genomic RNA and processed into four nsPs. nsP3 has a highly conserved macrodomain (MD) that binds ADP-ribose (ADPr), which can be conjugated to protein as a posttranslational modification involving transfer of ADPr from NAD+ by poly ADPr polymerases (PARPs). The nsP3MD also removes ADPr from mono ADP-ribosylated (MARylated) substrates. To determine which aspects of alphavirus replication require nsP3MD ADPr-binding and/or hydrolysis function, we studied NSC34 neuronal cells infected with chikungunya virus (CHIKV). Infection induced ADP-ribosylation of cellular proteins without increasing PARP expression, and inhibition of MARylation decreased virus replication. CHIKV with a G32S mutation that reduced ADPr-binding and hydrolase activities was less efficient than WT CHIKV in establishing infection and in producing nsPs, dsRNA, viral RNA, and infectious virus. CHIKV with a Y114A mutation that increased ADPr binding but reduced hydrolase activity, established infection like WT CHIKV, rapidly induced nsP translation, and shut off host protein synthesis with reduced amplification of dsRNA. To assess replicase function independent of virus infection, a transreplicase system was used. Mutant nsP3MDs D10A, G32E, and G112E with no binding or hydrolase activity had no replicase activity, G32S had little, and Y114A was intermediate to WT. Therefore, ADP ribosylation of proteins and nsP3MD ADPr binding are necessary for initiation of alphavirus replication, while hydrolase activity facilitates amplification of replication complexes. These observations are consistent with observed nsP3MD conservation and limited tolerance for mutation.}, } @article {pmid30322910, year = {2018}, author = {Eichstaedt, JC and Smith, RJ and Merchant, RM and Ungar, LH and Crutchley, P and Preoţiuc-Pietro, D and Asch, DA and Schwartz, HA}, title = {Facebook language predicts depression in medical records.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11203-11208}, pmid = {30322910}, issn = {1091-6490}, mesh = {Adult ; Depression/*psychology ; Depressive Disorder/*psychology ; Electronic Health Records/*statistics & numerical data ; Female ; Humans ; Language ; Male ; Social Media/*statistics & numerical data ; Surveys and Questionnaires ; }, abstract = {Depression, the most prevalent mental illness, is underdiagnosed and undertreated, highlighting the need to extend the scope of current screening methods. Here, we use language from Facebook posts of consenting individuals to predict depression recorded in electronic medical records. We accessed the history of Facebook statuses posted by 683 patients visiting a large urban academic emergency department, 114 of whom had a diagnosis of depression in their medical records. Using only the language preceding their first documentation of a diagnosis of depression, we could identify depressed patients with fair accuracy [area under the curve (AUC) = 0.69], approximately matching the accuracy of screening surveys benchmarked against medical records. Restricting Facebook data to only the 6 months immediately preceding the first documented diagnosis of depression yielded a higher prediction accuracy (AUC = 0.72) for those users who had sufficient Facebook data. Significant prediction of future depression status was possible as far as 3 months before its first documentation. We found that language predictors of depression include emotional (sadness), interpersonal (loneliness, hostility), and cognitive (preoccupation with the self, rumination) processes. Unobtrusive depression assessment through social media of consenting individuals may become feasible as a scalable complement to existing screening and monitoring procedures.}, } @article {pmid30322909, year = {2018}, author = {Bernhardt, ML and Stein, P and Carvacho, I and Krapp, C and Ardestani, G and Mehregan, A and Umbach, DM and Bartolomei, MS and Fissore, RA and Williams, CJ}, title = {TRPM7 and CaV3.2 channels mediate Ca2+ influx required for egg activation at fertilization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10370-E10378}, pmid = {30322909}, issn = {1091-6490}, support = {R01 HD051872/HD/NICHD NIH HHS/United States ; R01 HD092499/HD/NICHD NIH HHS/United States ; ZIA ES102985/ES/NIEHS NIH HHS/United States ; R37 GM051279/GM/NIGMS NIH HHS/United States ; ZIA ES103126/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Calcium Channels, T-Type/*metabolism ; Calcium Signaling/*physiology ; Cell Membrane/metabolism ; Cytoplasm/metabolism ; Female ; Fertilization/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Oocytes/metabolism ; Spermatozoa/metabolism ; Stromal Interaction Molecule 1/metabolism ; TRPM Cation Channels/*metabolism ; Zygote/*metabolism ; }, abstract = {The success of mammalian development following fertilization depends on a series of transient increases in egg cytoplasmic Ca2+, referred to as Ca2+ oscillations. Maintenance of these oscillations requires Ca2+ influx across the plasma membrane, which is mediated in part by T-type, CaV3.2 channels. Here we show using genetic mouse models that TRPM7 channels are required to support this Ca2+ influx. Eggs lacking both TRPM7 and CaV3.2 stop oscillating prematurely, indicating that together they are responsible for the majority of Ca2+ influx immediately following fertilization. Fertilized eggs lacking both channels also frequently display delayed resumption of Ca2+ oscillations, which appears to require sperm-egg fusion. TRPM7 and CaV3.2 channels almost completely account for Ca2+ influx observed following store depletion, a process previously attributed to canonical store-operated Ca2+ entry mediated by STIM/ORAI interactions. TRPM7 serves as a membrane sensor of extracellular Mg2+ and Ca2+ concentrations and mediates the effects of these ions on Ca2+ oscillation frequency. When bred to wild-type males, female mice carrying eggs lacking TRPM7 and CaV3.2 are subfertile, and their offspring have increased variance in postnatal weight. These in vivo findings confirm previous observations linking in vitro experimental alterations in Ca2+ oscillatory patterns with developmental potential and offspring growth. The identification of TRPM7 and CaV3.2 as key mediators of Ca2+ influx following fertilization provides a mechanistic basis for the rational design of culture media that optimize developmental potential in research animals, domestic animals, and humans.}, } @article {pmid30322908, year = {2018}, author = {Sumner, CJ and Wells, TT and Bergevin, C and Sollini, J and Kreft, HA and Palmer, AR and Oxenham, AJ and Shera, CA}, title = {Mammalian behavior and physiology converge to confirm sharper cochlear tuning in humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11322-11326}, pmid = {30322908}, issn = {1091-6490}, support = {R01 DC003687/DC/NIDCD NIH HHS/United States ; R01 DC012262/DC/NIDCD NIH HHS/United States ; MC_UU_00010/1//Medical Research Council/United Kingdom ; U135097127//Medical Research Council/United Kingdom ; }, mesh = {Acoustic Stimulation/methods ; Acoustics ; Animals ; Auditory Threshold/physiology ; Cochlea/*physiology ; Hearing/physiology ; Humans ; Mammals/*physiology ; Otoacoustic Emissions, Spontaneous/physiology ; Perceptual Masking/physiology ; Sound ; }, abstract = {Frequency analysis of sound by the cochlea is the most fundamental property of the auditory system. Despite its importance, the resolution of this frequency analysis in humans remains controversial. The controversy persists because the methods used to estimate tuning in humans are indirect and have not all been independently validated in other species. Some data suggest that human cochlear tuning is considerably sharper than that of laboratory animals, while others suggest little or no difference between species. We show here in a single species (ferret) that behavioral estimates of tuning bandwidths obtained using perceptual masking methods, and objective estimates obtained using otoacoustic emissions, both also employed in humans, agree closely with direct physiological measurements from single auditory-nerve fibers. Combined with human behavioral data, this outcome indicates that the frequency analysis performed by the human cochlea is of significantly higher resolution than found in common laboratory animals. This finding raises important questions about the evolutionary origins of human cochlear tuning, its role in the emergence of speech communication, and the mechanisms underlying our ability to separate and process natural sounds in complex acoustic environments.}, } @article {pmid30322907, year = {2018}, author = {Ron, R and Fragman-Sapir, O and Kadmon, R}, title = {Dispersal increases ecological selection by increasing effective community size.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11280-11285}, pmid = {30322907}, issn = {1091-6490}, mesh = {Biodiversity ; Biological Evolution ; Demography/statistics & numerical data ; *Ecology ; *Ecosystem ; *Population Density ; Population Dynamics/*trends ; }, abstract = {Selection and drift are universally accepted as the cornerstones of evolutionary changes. Recent theories extend this view to ecological changes, arguing that any change in species composition is driven by deterministic fitness differences among species (enhancing selection) and/or stochasticity in birth and death rates of individuals within species (enhancing drift). These forces have contrasting effects on the predictability of ecological dynamics, and thus understanding the factors affecting their relative importance is crucial for understanding ecological dynamics. Here we test the hypothesis that dispersal increases the relative importance of ecological selection by increasing the effective size of the community (i.e., the size relevant for competitive interactions and drift). According to our hypothesis, dispersal increases the effective size of the community by mixing individuals from different localities. This effect diminishes the relative importance of demographic stochasticity, thereby reducing drift and increasing the relative importance of selective forces as drivers of species composition. We tested our hypothesis, which we term the "effective community size" hypothesis, using two independent experiments focusing on annual plants: a field experiment in which we manipulated the magnitude of dispersal and a mesocosm experiment in which we directly manipulated the effective size of the communities. Both experiments, as well as related model simulations, were consistent with the hypothesis that increasing dispersal increases the role of selective forces as drivers of species composition. This finding has important implications for our understanding of the fundamental forces affecting community dynamics, as well as the management of species diversity, particularly in patchy and fragmented environments.}, } @article {pmid30322906, year = {2018}, author = {Bastiaansen, R and Jaïbi, O and Deblauwe, V and Eppinga, MB and Siteur, K and Siero, E and Mermoz, S and Bouvet, A and Doelman, A and Rietkerk, M}, title = {Multistability of model and real dryland ecosystems through spatial self-organization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11256-11261}, pmid = {30322906}, issn = {1091-6490}, mesh = {Biomass ; Conservation of Natural Resources/methods ; Diffusion ; *Ecosystem ; *Models, Biological ; }, abstract = {Spatial self-organization of dryland vegetation constitutes one of the most promising indicators for an ecosystem's proximity to desertification. This insight is based on studies of reaction-diffusion models that reproduce visual characteristics of vegetation patterns observed on aerial photographs. However, until now, the development of reliable early warning systems has been hampered by the lack of more in-depth comparisons between model predictions and real ecosystem patterns. In this paper, we combined topographical data, (remotely sensed) optical data, and in situ biomass measurements from two sites in Somalia to generate a multilevel description of dryland vegetation patterns. We performed an in-depth comparison between these observed vegetation pattern characteristics and predictions made by the extended-Klausmeier model for dryland vegetation patterning. Consistent with model predictions, we found that for a given topography, there is multistability of ecosystem states with different pattern wavenumbers. Furthermore, observations corroborated model predictions regarding the relationships between pattern wavenumber, total biomass, and maximum biomass. In contrast, model predictions regarding the role of slope angles were not corroborated by the empirical data, suggesting that inclusion of small-scale topographical heterogeneity is a promising avenue for future model development. Our findings suggest that patterned dryland ecosystems may be more resilient to environmental change than previously anticipated, but this enhanced resilience crucially depends on the adaptive capacity of vegetation patterns.}, } @article {pmid30322905, year = {2018}, author = {Ravindran, S}, title = {Profile of Julian I. Schroeder.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11109-11111}, pmid = {30322905}, issn = {1091-6490}, mesh = {Humans ; *Laboratory Personnel ; Plants ; Research ; }, } @article {pmid30322887, year = {2018}, author = {Denny, SK and Greenleaf, WJ}, title = {Linking RNA Sequence, Structure, and Function on Massively Parallel High-Throughput Sequencers.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032300}, pmid = {30322887}, issn = {1943-0264}, abstract = {SUMMARYHigh-throughput sequencing methods have revolutionized our ability to catalog the diversity of RNAs and RNA-protein interactions that can exist in our cells. However, the relationship between RNA sequence, structure, and function is enormously complex, demonstrating the need for methods that can provide quantitative thermodynamic and kinetic measurements of macromolecular interaction with RNA, at a scale commensurate with the sequence diversity of RNA. Here, we discuss a class of methods that extend the core functionality of DNA sequencers to enable high-throughput measurements of RNA folding and RNA-protein interactions. Topics discussed include a description of the method and multiple applications to RNA-binding proteins, riboswitch design and engineering, and RNA tertiary structure energetics.}, } @article {pmid30322750, year = {2018}, author = {Duron, O and Doublet, P and Vavre, F and Bouchon, D}, title = {The Importance of Revisiting Legionellales Diversity.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1027-1037}, doi = {10.1016/j.pt.2018.09.008}, pmid = {30322750}, issn = {1471-5007}, abstract = {Bacteria of the order Legionellales, such as Legionella pneumophila, the agent of Legionnaires' disease, and Coxiella burnetii, the agent of Q fever, are widely recognized as human pathogens. While our view of the Legionellales is often limited to clinical isolates, ecological surveys are continually uncovering new members of the Legionellales that do not fall into the recognized pathogenic species. Here we emphasize that most of these Legionellales are nonpathogenic forms that have evolved symbiotic lifestyles with nonvertebrate hosts. The diversity of nonpathogenic forms remains, however, largely underexplored. We conjecture that its characterization, once contrasted with the data on pathogenic species, will reveal novel highlights on the mechanisms underlying lifestyle transitions of intracellular bacteria, including the emergence of pathogenesis and mutualism, transmission routes, and host specificity.}, } @article {pmid30322741, year = {2018}, author = {Kilcher, S and Loessner, MJ}, title = {Engineering Bacteriophages as Versatile Biologics.}, journal = {Trends in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.tim.2018.09.006}, pmid = {30322741}, issn = {1878-4380}, abstract = {Viruses of bacteria (bacteriophages or phages) are highly evolved nanomachines that recognize bacterial cell walls, deliver genetic information, and kill or transform their targets with unparalleled specificity. For a long time, the use of genetically modified phages was limited to phage display approaches and fundamental research. This is mostly because phage engineering has been a complex and time-consuming task, applicable for only a few well characterized model phages. Recent advances in sequencing technology and molecular biology gave rise to rapid and precise tools that enable modification of less-well-characterized phages. These methods will pave the way for the development of modular designer-phages as versatile biologics that efficiently control multidrug-resistant bacteria and provide novel tools for pathogen detection, drug development, and beyond.}, } @article {pmid30322659, year = {2018}, author = {Key, A and Merritt, SR and Kivell, TL}, title = {Hand grip diversity and frequency during the use of Lower Palaeolithic stone cutting-tools.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {137-158}, doi = {10.1016/j.jhevol.2018.08.006}, pmid = {30322659}, issn = {1095-8606}, abstract = {The suite of anatomical features contributing to the unique gripping capabilities of the modern human hand evolved alongside the proliferation of Lower Palaeolithic flaked tool technologies across the Old World. Experimental studies investigating their potential co-evolution suggest that the use of flakes, handaxes, and other stone tools is facilitated by manipulative capabilities consistent with the evolutionary trajectory of the hominin hand during this period. Grip analyses have provided important contributions to this understanding. To date, however, there has been no large-scale investigation of grip diversity during flaked stone-tool use, empirical comparative analyses of grip use frequencies, or examination of ergonomic relationships between grip choice and stone tool type and form. Here, we conduct four experimental studies, using replica Lower Palaeolithic stone tools in a series of actualistic and laboratory-based contexts, to record grip type and frequency of grip use during 1067 stone tool-use events by 123 individuals. Using detailed morphometric data recorded from each tool, we demonstrate how grip choice varies according to the type and form of stone tool used, and how these relationships differ between tool-use contexts. We identify 29 grip types across all tool-use events, with significant differences recorded in their frequency of use dependent on tool type, tool form, and the context of use. Despite the influence of these three factors, there is consistency in the frequent use of a limited number (≤4) of grip types within each experiment and the consistent and seemingly forceful recruitment of the thumb and index finger. Accordingly, we argue that there are deep-rooted, ergonomically-related, regularities in how stone tools are gripped during their use, that these regularities may have been present during the use of stone tools by Plio-Pleistocene hominins, and any subsequent selective pressures would likely have been focused on the first and second digit.}, } @article {pmid30322384, year = {2018}, author = {Weiss, RA}, title = {Open questions: knowing who's who in multicellular animals is not always as simple as we imagine.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {115}, pmid = {30322384}, issn = {1741-7007}, abstract = {The ability of certain tumor cells of mammals and molluscs to spread from the original host to others reopens the question of distinguishing self from non-self. It is part of a wider phenomenon of cellular parasitism and cell chimerism including germ cells.}, } @article {pmid30321698, year = {2019}, author = {Dinis, M and Merabet, K and Martínez-Freiría, F and Steinfartz, S and Vences, M and Burgon, JD and Elmer, KR and Donaire, D and Hinckley, A and Fahd, S and Joger, U and Fawzi, A and Slimani, T and Velo-Antón, G}, title = {Allopatric diversification and evolutionary melting pot in a North African Palearctic relict: The biogeographic history of Salamandra algira.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {81-91}, doi = {10.1016/j.ympev.2018.10.018}, pmid = {30321698}, issn = {1095-9513}, abstract = {North Africa is a climatically and topographically complex region with unique biotic assemblages resulting from the combination of multiple biogeographic realms. Here, we assess the role of climate in promoting intra-specific diversification in a Palearctic relict, the North African fire salamander, Salamandra algira, using a combination of phylogenetic and population genetic analyses, paleoclimatic modelling and niche overlap tests. We used mitochondrial DNA (Cyt-b), 9838 ddRADseq loci, and 14 microsatellite loci to characterize patterns of genetic diversity and population structure. Phylogenetic analyses recover two major clades, each including several lineages with mito-nuclear discordances suggesting introgressive patterns between lineages in the Middle Atlas, associated with a melting pot of genetic diversity. Paleoclimatic modelling identified putative climatic refugia, largely matching areas of high genetic diversity, and supports the role of aridity in promoting allopatric diversification associated with ecological niche conservatism. Overall, our results highlight the role of climatic microrefugia as drivers of populations' persistence and diversification in the face of climatic oscillations in North Africa, and stress the importance of accounting for different genomic regions when reconstructing biogeographic processes from molecular markers.}, } @article {pmid30321697, year = {2019}, author = {Krásová, J and Mikula, O and Mazoch, V and Bryja, J and Říčan, O and Šumbera, R}, title = {Evolution of the Grey-bellied pygmy mouse group: Highly structured molecular diversity with predictable geographic ranges but morphological crypsis.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {143-155}, doi = {10.1016/j.ympev.2018.10.016}, pmid = {30321697}, issn = {1095-9513}, abstract = {The grey-bellied pygmy mouse (Mus triton) from the endemic African subgenus Nannomys is a widespread rodent species inhabiting the highlands of eastern and central Africa. Although it has long been considered as a single species, recent data has suggested the existence of a species complex. In order to evaluate the geographical structure and current taxonomy of M. triton, we analysed one mitochondrial and six nuclear genes from individuals covering most of its distribution range. Our analysis revealed the existence of at least five distinct genetic lineages with only marginal overlaps among their distributional ranges. Morphological comparisons, however, showed large overlaps in external body measurements and only a weak differentiation in skull form. Therefore, we suggest maintaining M. triton as a single taxon with pronounced intraspecific genetic structure. Divergence dating analysis placed the most recent common ancestor of the extant lineages of M. triton to the early Pleistocene (about 2.0 Ma). The phylogeographic structure of the species was likely shaped by Pleistocene climatic oscillations and the highly diverse topography of eastern Africa.}, } @article {pmid30321696, year = {2019}, author = {Cai, T and Cibois, A and Alström, P and Moyle, RG and Kennedy, JD and Shao, S and Zhang, R and Irestedt, M and Ericson, PGP and Gelang, M and Qu, Y and Lei, F and Fjeldså, J}, title = {Near-complete phylogeny and taxonomic revision of the world's babblers (Aves: Passeriformes).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {346-356}, doi = {10.1016/j.ympev.2018.10.010}, pmid = {30321696}, issn = {1095-9513}, abstract = {The babblers are a diverse group of passerine birds comprising 452 species. The group was long regarded as a "scrap basket" in taxonomic classification schemes. Although several studies have assessed the phylogenetic relationships for subsets of babblers during the past two decades, a comprehensive phylogeny of this group has been lacking. In this study, we used five mitochondrial and seven nuclear loci to generate a dated phylogeny for babblers. This phylogeny includes 402 species (ca. 89% of the overall clade) from 75 genera (97%) and all five currently recognized families, providing a robust basis for taxonomic revision. Our phylogeny supports seven major clades and reveals several non-monophyletic genera. Divergence time estimates indicate that the seven major clades diverged around the same time (18-20 million years ago, Ma) in the early Miocene. We use the phylogeny in a consistent way to propose a new taxonomy, with seven families and 64 genera of babblers, and a new linear sequence of names.}, } @article {pmid30321695, year = {2019}, author = {Stervander, M and Ryan, PG and Melo, M and Hansson, B}, title = {The origin of the world's smallest flightless bird, the Inaccessible Island Rail Atlantisia rogersi (Aves: Rallidae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {92-98}, doi = {10.1016/j.ympev.2018.10.007}, pmid = {30321695}, issn = {1095-9513}, abstract = {Rails (Aves: Rallidae) are renowned for their extreme dispersal capability, which has given rise to numerous island lineages. Many insular species lost the ability to fly as a response to release from predator pressure-a feature causing rapid extinction when humans subsequently introduced mammals. The world's smallest extant flightless bird, the Inaccessible Island Rail Atlantisia rogersi, is endemic to Inaccessible Island, Tristan da Cunha archipelago, in the central South Atlantic Ocean. It is placed in a monotypic genus, but its taxonomic affinity, as well as geographic origin, are disputed. Contrary to its suggested Old World origin, we demonstrate that the Inaccessible Island Rail is nested within the mainly South American 'Laterallus clade' and that it colonized ≥3 million-year-old Inaccessible Island from South America c. 1.5 million years ago. The taxonomy of rails has traditionally been based on morphology, and convergent evolution has caused many cases of misclassification. We suggest a re-classification within the 'Laterallus clade' and call for extended coverage of taxon sampling for DNA sequencing.}, } @article {pmid30321694, year = {2019}, author = {Tamashiro, RA and White, ND and Braun, MJ and Faircloth, BC and Braun, EL and Kimball, RT}, title = {What are the roles of taxon sampling and model fit in tests of cyto-nuclear discordance using avian mitogenomic data?.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {132-142}, doi = {10.1016/j.ympev.2018.10.008}, pmid = {30321694}, issn = {1095-9513}, abstract = {Conflicts between nuclear and mitochondrial phylogenies have led to uncertainty for some relationships within the tree of life. These conflicts have led some to question the value of mitochondrial DNA in phylogenetics now that genome-scale nuclear data can be readily obtained. However, since mitochondrial DNA is maternally inherited and does not recombine, its phylogeny should be closer to the species tree. Additionally, its rapid evolutionary rate may drive accumulation of mutations along short internodes where relevant information from nuclear loci may be limited. In this study, we examine the mitochondrial phylogeny of Cavitaves to elucidate its congruence with recently published nuclear phylogenies of this group of birds. Cavitaves includes the orders Trogoniformes (trogons), Bucerotiformes (hornbills), Coraciiformes (kingfishers and allies), and Piciformes (woodpeckers and allies). We hypothesized that sparse taxon sampling in previously published mitochondrial trees was responsible for apparent cyto-nuclear discordance. To test this hypothesis, we assembled 27 additional Cavitaves mitogenomes and estimated phylogenies using seven different taxon sampling schemes ranging from five to 42 ingroup species. We also tested the role that partitioning and model choice played in the observed discordance. Our analyses demonstrated that improved taxon sampling could resolve many of the disagreements. Similarly, partitioning was valuable in improving congruence with the topology from nuclear phylogenies, though the model used to generate the mitochondrial phylogenies had less influence. Overall, our results suggest that the mitochondrial tree is trustworthy when partitioning is used with suitable taxon sampling.}, } @article {pmid30321355, year = {2018}, author = {McGrath, C}, title = {Highlight: The Evolutionary Arsenal of Aphids.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2734-2735}, pmid = {30321355}, issn = {1759-6653}, } @article {pmid30321345, year = {2018}, author = {Ward, CM and Baxter, SW}, title = {Assessing Genomic Admixture between Cryptic Plutella Moth Species following Secondary Contact.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2973-2985}, pmid = {30321345}, issn = {1759-6653}, abstract = {Cryptic species are genetically distinct taxa without obvious variation in morphology and are occasionally discovered using molecular or sequence data sets of populations previously thought to be a single species. The world-wide Brassica pest, Plutella xylostella (diamondback moth), has been a problematic insect in Australia since 1882, yet a morphologically cryptic species with apparent endemism (P. australiana) was only recognized in 2013. Plutella xylostella and P. australiana are able to hybridize under laboratory conditions, and it was unknown whether introgression of adaptive traits could occur in the field to improve fitness and potentially increase pressure on agriculture. Phylogenetic reconstruction of 29 nuclear genomes confirmed P. xylostella and P. australiana are divergent, and molecular dating with 13 mitochondrial genes estimated a common Plutella ancestor 1.96 ± 0.175 Ma. Sympatric Australian populations and allopatric Hawaiian P. xylostella populations were used to test whether neutral or adaptive introgression had occurred between the two Australian species. We used three approaches to test for genomic admixture in empirical and simulated data sets including 1) the f3 statistic at the level of the population, 2) pairwise comparisons of Nei's absolute genetic divergence (dXY) between populations, and 3) changes in phylogenetic branch lengths between individuals across 50-kb genomic windows. These complementary approaches all supported reproductive isolation of the Plutella species in Australia, despite their ability to hybridize. Finally, we highlight the most divergent genomic regions between the two cryptic Plutella species and find they contain genes involved with processes including digestion, detoxification, and DNA binding.}, } @article {pmid30321344, year = {2018}, author = {Carriel, D and Simon Garcia, P and Castelli, F and Lamourette, P and Fenaille, F and Brochier-Armanet, C and Elsen, S and Gutsche, I}, title = {A Novel Subfamily of Bacterial AAT-Fold Basic Amino Acid Decarboxylases and Functional Characterization of Its First Representative: Pseudomonas aeruginosa LdcA.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3058-3075}, pmid = {30321344}, issn = {1759-6653}, abstract = {Polyamines are small amino-acid derived polycations capable of binding negatively charged macromolecules. Bacterial polyamines are structurally and functionally diverse, and are mainly produced biosynthetically by pyridoxal-5-phosphate-dependent amino acid decarboxylases referred to as Lysine-Arginine-Ornithine decarboxylases (LAOdcs). In a phylogenetically limited group of bacteria, LAOdcs are also induced in response to acid stress. Here, we performed an exhaustive phylogenetic analysis of the AAT-fold LAOdcs which showcased the ancient nature of their short forms in Cyanobacteria and Firmicutes, and emergence of distinct subfamilies of long LAOdcs in Proteobacteria. We identified a novel subfamily of lysine decarboxylases, LdcA, ancestral in Betaproteobacteria and Pseudomonadaceae. We analyzed the expression of LdcA from Pseudomonas aeruginosa, and uncovered its role, intimately linked to cadaverine (Cad) production, in promoting growth and reducing persistence of this multidrug resistant human pathogen during carbenicillin treatment. Finally, we documented a certain redundancy in the function of the three main polyamines-Cad, putrescine (Put), and spermidine (Spd)-in P. aeruginosa by demonstrating the link between their intracellular level, as well as the capacity of Put and Spd to complement the growth phenotype of the ldcA mutant.}, } @article {pmid30321343, year = {2018}, author = {Margres, MJ and Ruiz-Aravena, M and Hamede, R and Jones, ME and Lawrance, MF and Hendricks, SA and Patton, A and Davis, BW and Ostrander, EA and McCallum, H and Hohenlohe, PA and Storfer, A}, title = {The Genomic Basis of Tumor Regression in Tasmanian Devils (Sarcophilus harrisii).}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3012-3025}, pmid = {30321343}, issn = {1759-6653}, support = {P30 GM103324/GM/NIGMS NIH HHS/United States ; R01 GM126563/GM/NIGMS NIH HHS/United States ; }, abstract = {Understanding the genetic basis of disease-related phenotypes, such as cancer susceptibility, is crucial for the advancement of personalized medicine. Although most cancers are somatic in origin, a small number of transmissible cancers have been documented. Two such cancers have emerged in the Tasmanian devil (Sarcophilus harrisii) and now threaten the species with extinction. Recently, cases of natural tumor regression in Tasmanian devils infected with the clonally contagious cancer have been detected. We used whole-genome sequencing and FST-based approaches to identify the genetic basis of tumor regression by comparing the genomes of seven individuals that underwent tumor regression with those of three infected individuals that did not. We found three highly differentiated candidate genomic regions containing several genes related to immune response and/or cancer risk, indicating that the genomic basis of tumor regression was polygenic. Within these genomic regions, we identified putative regulatory variation in candidate genes but no nonsynonymous variation, suggesting that natural tumor regression may be driven, at least in part, by differential host expression of key loci. Comparative oncology can provide insight into the genetic basis of cancer risk, tumor development, and the pathogenicity of cancer, particularly due to our limited ability to monitor natural, untreated tumor progression in human patients. Our results support the hypothesis that host immune response is necessary for triggering tumor regression, providing candidate genes that may translate to novel treatments in human and nonhuman cancers.}, } @article {pmid30321329, year = {2018}, author = {Marek, A and Tomala, K}, title = {The Contribution of Purifying Selection, Linkage, and Mutation Bias to the Negative Correlation between Gene Expression and Polymorphism Density in Yeast Populations.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2986-2996}, pmid = {30321329}, issn = {1759-6653}, abstract = {The negative correlation between the rate of protein evolution and expression level of a gene has been recognized as a universal law of the evolutionary biology (Koonin 2011). In our study, we apply a population-based approach to systematically investigate the relative importance of unequal mutation rate, linkage, and selection in the origin of the expression-polymorphism anticorrelation. We analyzed the DNA sequence of protein coding genes of 24 Saccharomyces cerevisiae and 58 Schizosaccharomyces pombe strains. We found that highly expressed genes had a substantially decreased number of polymorphic sites when compared with genes transcribed less extensively. This expression-dependent reduction was especially strong in the nonsynonymous sites, although it was also present in the synonymous sites and untranslated regions, both up and down of a gene. Most importantly, no such trend was found in introns. We used these observations, as well as analyses of site frequency spectra and data from mutation accumulation experiments, to show that the purifying selection acting on nonsynonymous sites was the main, but not exclusive, factor impeding molecular evolution within the coding sequences of highly expressed genes. Linkage could not fully explain the observed pattern of polymorphism within the untranslated regions and synonymous sites, although the contribution of selection acting directly on synonymous variants was extremely small. Finally, we found that the impact of mutational bias was rather negligible.}, } @article {pmid30321324, year = {2018}, author = {Rouard, M and Droc, G and Martin, G and Sardos, J and Hueber, Y and Guignon, V and Cenci, A and Geigle, B and Hibbins, MS and Yahiaoui, N and Baurens, FC and Berry, V and Hahn, MW and D'Hont, A and Roux, N}, title = {Three New Genome Assemblies Support a Rapid Radiation in Musa acuminata (Wild Banana).}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3129-3140}, pmid = {30321324}, issn = {1759-6653}, abstract = {Edible bananas result from interspecific hybridization between Musa acuminata and Musa balbisiana, as well as among subspecies in M. acuminata. Four particular M. acuminata subspecies have been proposed as the main contributors of edible bananas, all of which radiated in a short period of time in southeastern Asia. Clarifying the evolution of these lineages at a whole-genome scale is therefore an important step toward understanding the domestication and diversification of this crop. This study reports the de novo genome assembly and gene annotation of a representative genotype from three different subspecies of M. acuminata. These data are combined with the previously published genome of the fourth subspecies to investigate phylogenetic relationships. Analyses of shared and unique gene families reveal that the four subspecies are quite homogenous, with a core genome representing at least 50% of all genes and very few M. acuminata species-specific gene families. Multiple alignments indicate high sequence identity between homologous single copy-genes, supporting the close relationships of these lineages. Interestingly, phylogenomic analyses demonstrate high levels of gene tree discordance, due to both incomplete lineage sorting and introgression. This pattern suggests rapid radiation within Musa acuminata subspecies that occurred after the divergence with M. balbisiana. Introgression between M. a. ssp. malaccensis and M. a. ssp. burmannica was detected across the genome, though multiple approaches to resolve the subspecies tree converged on the same topology. To support evolutionary and functional analyses, we introduce the PanMusa database, which enables researchers to exploration of individual gene families and trees.}, } @article {pmid30320546, year = {2018}, author = {Noda, S and Sakamoto, M and Aihara, C and Yuki, M and Katsuhara, M and Ohkuma, M}, title = {Lactococcus termiticola sp. nov., isolated from the gut of the wood-feeding higher termite Nasutitermes takasagoensis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3832-3836}, doi = {10.1099/ijsem.0.003068}, pmid = {30320546}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Isoptera/*microbiology ; Lactococcus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Wood ; }, abstract = {A strain of lactic acid bacteria, designated NtB2T, isolated from the gut of the wood-feeding higher termite Nasutitermes takasagoensis, was characterized genetically and phenotypically. Strain NtB2T was related to Lactococcus lacti subsp. tructae JCM 31125T isolated from brown trout, showing 93.2 and 81.0 % similarity in 16S rRNA gene and rpoB gene sequences, respectively. Furthermore, genomic comparisons using pairwise average nucleotide identity analysis and the Genome-to-Genome Distance Calculator between strain NtB2T and L. lacti subsp. tructae JCM 31125T gave values of 81.0 and 23.2 %, respectively. Major cellular fatty acids produced by strain NtB2T were C18 : 1ω9c and C16 : 0. The cell-wall peptidoglycan type of strain NtB2T was A3α, Lys-Gly-Ser-Ala2. Based on the data presented, the isolate represents a novel species of the genus Lactococcus, for which the name Lactococcus termiticola sp. nov. is proposed. The type strain is NtB2T (=JCM 32569T=DSM 107259T).}, } @article {pmid30320544, year = {2018}, author = {Sheu, SY and Su, CL and Chen, WM}, title = {Flavobacterium riviphilum sp. nov., isolated from a freshwater creek.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3844-3850}, doi = {10.1099/ijsem.0.003070}, pmid = {30320544}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Polyamines/chemistry ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; Taiwan ; Vitamin K 2/analogs & derivatives/chemistry ; Water Microbiology ; }, abstract = {A novel bacterium, designated strain TAPY6T, was isolated from a freshwater creek in Taiwan. The strain was Gram-stain-negative, strictly aerobic, motile-by-gliding, rod-shaped and formed translucent yellow colonies. Optimal growth occurred at 20-30 °C, pH 6 and in the absence of NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TAPY6T belonged to the genus Flavobacterium and was most closely related to Flavobacterium succinicans LMG 10402T (97.3 % sequence similarity) and Flavobacterium glycines Gm-149T (96.3 %). Strain TAPY6T contained C15 : 0 and iso-C15 : 0 as the predominant fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, five uncharacterized aminophospholipids, two uncharacterized phospholipids and one uncharacterized aminolipid. The major polyamine was homospermidine. The major isoprenoid quinone was MK-6. The DNA G+C content of the genomic DNA was 39.8 mol%. Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Flavobacterium. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain TAPY6T represents a novel species in the genus Flavobacterium, for which the name Flavobacterium riviphilum sp. nov. is proposed. The type strain is TAPY6T (=BCRC 81007T=LMG 29728T=KCTC 52444T).}, } @article {pmid30320543, year = {2018}, author = {Baek, C and Shin, SK and Yi, H}, title = {Flavobacterium magnum sp. nov., Flavobacterium pallidum sp. nov., Flavobacterium crocinum sp. nov. and Flavobacterium album sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3837-3843}, doi = {10.1099/ijsem.0.003067}, pmid = {30320543}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification ; Lakes/*microbiology ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Water Microbiology ; }, abstract = {Four new limnic bacterial strains, namely HYN0048T, HYN0049T, HYN0056T and HYN0059T, were isolated from two lakes in the Nakdong River water system in Korea. 16S rRNA gene sequence analyses indicated that strains HYN0048T, HYN0049T, HYN0056T and HYN0059T belonged to the genus Flavobacterium by showing the highest sequence similarities with the type strains of F. soli (94.9 %), F. keumense (95.1 %), F. dispersum (97.7 %) and F. hauense (97.6 %), respectively. The low sequence similarities and tree topologies implied the novelty of the four isolates, as novel genomic species of the genus Flavobacterium. Numerous physiological and biochemical features also supported the distinctiveness of the isolates from previously known bacterial species. On the basis of the phylogenetic and phenotypic data presented in this study, four novel species are suggested with the following names: Flavobacterium magnum sp. nov. (type strain HYN0048T=KACC 19180T=NBRC 112740T), Flavobacterium pallidum sp. nov. (HYN0049T=KACC 19181T=NBRC 112741T), Flavobacterium crocinum sp. nov. (HYN0056T=KACC 19182T=NBRC 112743T) and Flavobacterium album sp. nov. (HYN0059T=KACC 19183T=NBRC 112744T).}, } @article {pmid30319239, year = {2018}, author = {von Rueden, C and Alami, S and Kaplan, H and Gurven, M}, title = {Sex differences in political leadership in an egalitarian society.}, journal = {Evolution and human behavior : official journal of the Human Behavior and Evolution Society}, volume = {39}, number = {4}, pages = {402-411}, pmid = {30319239}, issn = {1090-5138}, support = {R01 AG024119/AG/NIA NIH HHS/United States ; }, abstract = {We test the contribution of sex differences in physical formidability, education, and cooperation to the acquisition of political leadership in a small-scale society. Among forager-farmers from the Bolivian Amazon, we find that men are more likely to exercise different forms of political leadership, including verbal influence during community meetings, coordination of community projects, and dispute resolution. We show that these differences in leadership are not due to gender per se but are associated with men's greater number of cooperation partners, greater access to schooling, and greater body size and physical strength. Men's advantage in cooperation partner number is tied to their participation in larger groups and to the opportunity costs of women's intrahousehold labor. We argue these results highlight the mutual influence of sexual selection and the sexual division of labor in shaping how women and men acquire leadership.}, } @article {pmid30318817, year = {2018}, author = {Cai, M and Ma, S and Hu, R and Tomberlin, JK and Thomashow, LS and Zheng, L and Li, W and Yu, Z and Zhang, J}, title = {Rapidly mitigating antibiotic resistant risks in chicken manure by Hermetia illucens bioconversion with intestinal microflora.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4051-4062}, doi = {10.1111/1462-2920.14450}, pmid = {30318817}, issn = {1462-2920}, support = {41603110//National Natural Science Foundation of China/ ; 2017YFD0800200//National Key Technology R & D Program of China/ ; 2018YFF0213503//National Key Technology R & D Program of China/ ; 2018YFD0500203//National Key Technology R & D Program of China/ ; }, abstract = {Antibiotic resistance genes (ARGs) in animal manure are an environmental concern due to naturally occurring bacteria being exposed to these wastes and developing multidrug resistance. The bioconversion of manure with fly larvae is a promising alternative for recycling these wastes while attenuating ARGs. We investigated the impact of black soldier fly (BSF, Hermetia illucens) larval bioconversion of chicken manure on the persistence of associated ARGs. Compared with traditional composting or sterile larval treatments (by 48.4% or 88.7%), non-sterile BSF larval treatments effectively reduced ARGs and integrin genes by 95.0% during 12 days, due to rapid decreases in concentrations of the genes and associated bacteria as they passed through the larval gut and were affected by intestinal microbes. After larval treatments, bacterial community composition differed significantly, with the percentage of Firmicutes possibly carrying ARGs reduced by 65.5% or more. On average, human pathogenic bacteria populations declined by 70.7%-92.9%, effectively mitigating risks of these bacteria carrying ARGs. Environmental pH, nitrogen content and antibiotic concentrations were closely related to both bacterial community composition and targeted gene attenuation in larval systems. Selective pressures of larval gut environments with intestinal microbes, larval bacteriostasis and reformulation of manure due to larval digestion contributed to ARG attenuation.}, } @article {pmid30318768, year = {2018}, author = {Forchhammer, K and Schwarz, R}, title = {Nitrogen chlorosis in unicellular cyanobacteria - a developmental program for surviving nitrogen deprivation.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14447}, pmid = {30318768}, issn = {1462-2920}, support = {1708//GRK/ ; ISF 1245/10//Israel Science Foundation/ ; }, abstract = {Cyanobacteria evolved sophisticated mechanisms allowing them to cope with environmental depletion of combined nitrogen. Here, we describe progress in understanding the processes involved in acclimation of nondiazotrophic cyanobacteria to nitrogen shortage, known as nitrogen chlorosis. The process includes immediate metabolic changes and degradation of light harvesting complexes as well as long-term acclimation responses. Consequently, quiescent cells substantially differing from vegetative cells are obtained. Thus, the process leading to these considerable metabolic and morphological changes is referred to as a developmental program. Current understanding of the relevant regulatory processes depicts an intricate mechanism involving modulation of transcription activators by proteinaceous interacting components, as well as by small metabolites reporting the energy status and carbon-nitrogen balance of the cell. In addition, we describe in detail the quiescent state characterizing cells under prolonged starvation and the process of recovery from this dormant chlorotic state. Accumulated data provide an in depth understanding of the mechanisms accompanying the cycling of cyanobacterial cells between vegetative growth, the quiescent-state and the recovery program, allowing them to regain proliferative growth upon nutrient replenishment.}, } @article {pmid30318710, year = {2018}, author = {Liu, Y and Qin, Q and Defoirdt, T}, title = {Does quorum sensing interference affect the fitness of bacterial pathogens in the real world?.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3918-3926}, doi = {10.1111/1462-2920.14446}, pmid = {30318710}, issn = {1462-2920}, support = {//Special Research Fund of Ghent University/ ; 218043//Scientific Research Startup Fund of South China Agricultural University/ ; }, abstract = {Many bacterial pathogens rely on quorum sensing to control virulence gene expression. Based on numerous experiments conducted under well-defined conditions, quorum sensing interference is considered as a promising strategy to tackle infections and thus might have the potential to (partially) replace antibiotics. Despite the promising results in well-defined (artificial) laboratory experiments, there still is a lack of knowledge with respect to the impact of quorum sensing interference on the fitness of pathogens in more realistic scenarios, including interactions with a host, the external environment and complex microbial communities. In this article, we critically evaluate the current knowledge with respect to these three facets of the real world that can affect the fitness of quorum sensing bacterial pathogens. We argue that further research is needed in order to determine how these factors interplay with quorum sensing and to what extent they can influence the selective pressure that might be exerted by quorum sensing interference (and thus determine the risk of resistance development against quorum sensing interference). This kind of information is indispensable in order to optimize quorum sensing interference-based therapeutic strategies.}, } @article {pmid30318588, year = {2018}, author = {Velotta, JP and Ivy, CM and Wolf, CJ and Scott, GR and Cheviron, ZA}, title = {Maladaptive phenotypic plasticity in cardiac muscle growth is suppressed in high-altitude deer mice.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2712-2727}, doi = {10.1111/evo.13626}, pmid = {30318588}, issn = {1558-5646}, support = {NSERC Discovery Grant 418202-//Natural Sciences and Engineering Research Council of Canada/ ; 2012//Natural Sciences and Engineering Research Council of Canada/ ; IOS-1354934//Division of Integrative Organismal Systems/ ; IOS-1444161//Division of Integrative Organismal Systems/ ; OIA-1736249//Division of Integrative Organismal Systems/ ; F32 HL136124/HL/NHLBI NIH HHS/United States ; }, abstract = {How often phenotypic plasticity acts to promote or inhibit adaptive evolution is an ongoing debate among biologists. Recent work suggests that adaptive phenotypic plasticity promotes evolutionary divergence, though several studies have also suggested that maladaptive plasticity can potentiate adaptation. The role of phenotypic plasticity, adaptive, or maladaptive, in evolutionary divergence remains controversial. We examined the role of plasticity in evolutionary divergence between two species of Peromyscus mice that differ in native elevations. We used cardiac mass as a model phenotype, since ancestral hypoxia-induced responses of the heart may be both adaptive and maladaptive at high-altitude. While left ventricle growth should enhance oxygen delivery to tissues, hypertrophy of the right ventricle can lead to heart failure and death. We compared left- and right-ventricle plasticity in response to hypoxia between captive-bred P. leucopus (representing the ancestral lowland condition) and P. maniculatus from high-altitude. We found that maladaptive ancestral plasticity in right ventricle hypertrophy is reduced in high-altitude deer mice. Analysis of the heart transcriptome suggests that changes in expression of inflammatory signaling genes, particularly interferon regulatory factors, contribute to the suppression of right ventricle hypertrophy. We found weak evidence that adaptive plasticity of left ventricle mass contributes to evolution. Our results suggest that selection to suppress ancestral maladaptive plasticity plays a role in adaptation.}, } @article {pmid30318316, year = {2018}, author = {Subramanian, A and Sarkar, RR}, title = {Perspectives on Leishmania Species and Stage-specific Adaptive Mechanisms.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1068-1081}, doi = {10.1016/j.pt.2018.09.004}, pmid = {30318316}, issn = {1471-5007}, abstract = {The hurdles in drug and vaccine development pipelines for leishmaniasis, a complex, multifaceted disease, are largely due to the digenetic lifecycle, differential clinical manifestations of the parasite, and the incomplete understanding of its adaptations within its hosts. Here, we discuss the distinct computational and experimental techniques employed to identify the species and stage-specific adaptive mechanisms at different levels of biological organization, the progress made so far, and limitations in comprehending leishmaniasis as a systems biology disease. Based on the available perspectives, we also provide suggestions and requirements to tackle the growing challenges for bridging the genotype with the phenotype. A systems perspective can be instrumental in understanding the complexities of the disease and can provide insights for targeted control.}, } @article {pmid30318277, year = {2018}, author = {Tee, SH}, title = {Mechanism diagrams and abstraction-by-aggregation.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {71}, number = {}, pages = {17-25}, doi = {10.1016/j.shpsc.2018.10.003}, pmid = {30318277}, issn = {1879-2499}, mesh = {*Biological Science Disciplines ; Computer Graphics ; *Knowledge ; Models, Biological ; Research/*instrumentation ; *Research Design ; }, abstract = {Mechanism diagrams exhibit visually the organized parts and operations of a biological mechanism. A mechanism diagram can facilitate mechanistic research by providing a mechanistic explanation of the phenomenon of interest. Much research has been focusing on the mechanistic explanation and the explanatory mechanistic models. As a specific type of scientific diagram, a simple mechanism diagram can be explanatory by drawing on the rich explanatory resources of non-depicted background knowledge. The relationship between the visually depicted and the background knowledge is underexplored. It is unclear how the non-depicted background knowledge of a mechanism diagram contributes to providing a better-informed explanation of the phenomenon of interest in biological sciences. With the aim to explore this relationship, I articulate that a mechanism diagram provides a mechanistic explanation by a process called abstraction-by-aggregation. Through visual cues, the unified relevant background knowledge provides an epistemic access to a better-informed explanation.}, } @article {pmid30318266, year = {2019}, author = {Irwin, NAT and Tikhonenkov, DV and Hehenberger, E and Mylnikov, AP and Burki, F and Keeling, PJ}, title = {Phylogenomics supports the monophyly of the Cercozoa.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {416-423}, doi = {10.1016/j.ympev.2018.09.004}, pmid = {30318266}, issn = {1095-9513}, abstract = {The phylum Cercozoa consists of a diverse assemblage of amoeboid and flagellated protists that forms a major component of the supergroup, Rhizaria. However, despite its size and ubiquity, the phylogeny of the Cercozoa remains unclear as morphological variability between cercozoan species and ambiguity in molecular analyses, including phylogenomic approaches, have produced ambiguous results and raised doubts about the monophyly of the group. Here we sought to resolve these ambiguities using a 161-gene phylogenetic dataset with data from newly available genomes and deeply sequenced transcriptomes, including three new transcriptomes from Aurigamonas solis, Abollifer prolabens, and a novel species, Lapot gusevi n. gen. n. sp. Our phylogenomic analysis strongly supported a monophyletic Cercozoa, and approximately-unbiased tests rejected the paraphyletic topologies observed in previous studies. The transcriptome of L. gusevi represents the first transcriptomic data from the large and recently characterized Aquavolonidae-Treumulida-'Novel Clade 12' group, and phylogenomics supported its position as sister to the cercozoan subphylum, Endomyxa. These results provide insights into the phylogeny of the Cercozoa and the Rhizaria as a whole.}, } @article {pmid30317689, year = {2019}, author = {Briolat, ES and Zagrobelny, M and Olsen, CE and Blount, JD and Stevens, M}, title = {No evidence of quantitative signal honesty across species of aposematic burnet moths (Lepidoptera: Zygaenidae).}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {31-48}, doi = {10.1111/jeb.13389}, pmid = {30317689}, issn = {1420-9101}, support = {1355867//BBSRC/ ; DFF-1323-00088//Danish Council for Independent Research/ ; }, abstract = {Many defended species use conspicuous visual warning signals to deter potential predators from attacking. Traditional theory holds that these signals should converge on similar forms, yet variation in visual traits and the levels of defensive chemicals is common, both within and between species. It is currently unclear how the strength of signals and potency of defences might be related: conflicting theories suggest that aposematic signals should be quantitatively honest, or, in contrast, that investment in one component should be prioritized over the other, while empirical tests have yielded contrasting results. Here, we advance this debate by examining the relationship between defensive chemicals and signal properties in a family of aposematic Lepidoptera, accounting for phylogenetic relationships and quantifying coloration from the perspective of relevant predators. We test for correlations between toxin levels and measures of wing colour across 14 species of day-flying burnet and forester moths (Lepidoptera: Zygaenidae), protected by highly aversive cyanogenic glucosides, and find no clear evidence of quantitative signal honesty. Significant relationships between toxin levels and coloration vary between sexes and sampling years, and several trends run contrary to expectations for signal honesty. Although toxin concentration is positively correlated with increasing luminance contrast in forewing pattern in 1 year, higher toxin levels are also associated with paler and less chromatically salient markings, at least in females, in another year. Our study also serves to highlight important factors, including sex-specific trends and seasonal variation, that should be accounted for in future work on signal honesty in aposematic species.}, } @article {pmid30317405, year = {2019}, author = {Xu, Y and Lv, J and Xie, C and Sun, S and Ke, L and Chen, S}, title = {Halorubrum glutamatedens sp. nov., a Halophilic Archaeon Isolated from a Rock Salt.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {52-56}, doi = {10.1007/s00284-018-1583-0}, pmid = {30317405}, issn = {1432-0991}, support = {31460003//National Natural Science Foundation of China/ ; 591601//Anhui Provincial Key Laboratory of the Conservation and Exploitation of Biological Resources/ ; KJ2017A318//University Natural Science Research Project of Anhui Province (CN)/ ; gxyqZD2017011//Anhui Department of Education (CN)/ ; }, abstract = {An extremely halophilic archaeon, strain ZY8T, was isolated from a rock salt of Yunnan salt mine. It was able to grow at 12-30% (w/v) NaCl (optimum, 15-20%), pH 7.0-9.0 (optimum, pH 8.5), and 20-45 °C (optimum, 42 °C). Sequence similarity search of its 16S rRNA gene showed that strain ZY8T belonged to the genus Halorubrum, and it is closely related to species of H. aethiopicum SAH-A6T (98.6%), H. aquaticum EN-2T (98.6%), and H. halodurans Cb34T (98.5%), respectively. Strain ZY8T contained phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and phosphatidylglycerol sulfate as its major phospholipids, and a sulfated diglycosyl diether as its major glycolipid. The DNA G+C content was 66.7 mol%. DNA-DNA relatedness between strains ZY8T and closely related species were far below 70%. Based on the phenotypic and phylogenetic analyses, it is proposed that strain ZY8T represents a novel species of the genus Halorubrum, for which the name Halorubrum glutamatedens sp. nov. is proposed. The type strain is ZY8T (=CGMCC 1.16026T=NBRC 112866T).}, } @article {pmid30317152, year = {2018}, author = {De Niz, M and Heussler, VT}, title = {Rodent malaria models: insights into human disease and parasite biology.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {93-101}, doi = {10.1016/j.mib.2018.09.003}, pmid = {30317152}, issn = {1879-0364}, abstract = {The use of rodents as model organisms to study human disease is based on the genetic and physiological similarities between the species. Successful molecular methods to generate transgenic reporter or humanized rodents has rendered rodents as powerful tools for understanding biological processes and host-pathogen interactions relevant to humans. In malaria research, rodent models have been pivotal for the study of liver stages, syndromes arising from blood stages of infection, and malaria transmission to and from the mammalian host. Importantly, many in vivo findings are comparable to pathology observed in humans only when adequate combinations of rodent strains and Plasmodium parasites are used.}, } @article {pmid30317151, year = {2018}, author = {Blank, ML and Boyle, JP}, title = {Effector variation at tandem gene arrays in tissue-dwelling coccidia: who needs antigenic variation anyway?.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {86-92}, doi = {10.1016/j.mib.2018.09.001}, pmid = {30317151}, issn = {1879-0364}, support = {R01 AI114655/AI/NIAID NIH HHS/United States ; }, abstract = {Locus expansion and diversification is pervasive in apicomplexan genomes and is predominantly found in loci encoding secreted proteins that interact with factors outside of the parasite. Key for understanding the impact of each of these loci on the host requires identification and functional characterization of their protein products, but these repetitive loci often are refractory to genome assembly. In this review we focus on Toxoplasma gondii and its nearest relatives to highlight the known impact of duplicated and diversified loci on our understanding of the host-pathogen molecular arms race. We describe current tools used for the identification and characterization of these loci, and review the most recent examples of how gene-expansion driven diversification can lead to novel gene functions.}, } @article {pmid30317150, year = {2018}, author = {Musah-Eroje, M and Flynn, RJ}, title = {Fasciola hepatica, TGF-β and host mimicry: the enemy within.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {80-85}, doi = {10.1016/j.mib.2018.09.002}, pmid = {30317150}, issn = {1879-0364}, abstract = {Helminths parasites undergo developmental changes and migration within their definitive host, in addition to establishing chronic infection. Essential to this is the evasion of host immune responses; the canonical Th2 response is effective at removing parasites resident in the intestine. Conversely, helminths also promote the development of antigen-specific anergy and regulation. This often limits pathology but allows parasite survival, parasite effectors mediating this are the subject of intense study. They may be useful as future vaccine targets or xenogenic therapeutics. Fasciola hepatica possesses a family of TGF-like molecules of which one member, FhTLM, is capable of promoting intrinsic and extrinsic effects. Here we review the extrinsic effects of FhTLM on the host macrophage and its consequences for protective immunity. This review also discusses the specificities of FhTLM in light a very recent description of a nematode TGF-β mimic and the effects of endogenous TGF-β.}, } @article {pmid30316948, year = {2019}, author = {Wei, C and Dong, L and Li, SH and Alström, P and Liu, Y and Xia, C and Yao, CT and Zhang, Y}, title = {From the Himalayas to a continental Island: Integrative species delimitation in the Brownish-flanked Bush Warbler Horornis fortipes complex.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {219-227}, doi = {10.1016/j.ympev.2018.10.009}, pmid = {30316948}, issn = {1095-9513}, abstract = {As species serve as basic units of study in many fields of biology, assessments of species limits are fundamental for such studies. Here, we used a multilocus dataset and different coalescent-based methods to analyze species delimitation and phylogenetic relationships in the Brownish-flanked Bush Warbler Horornis fortipes complex, which is widespread in the Sino-Himalayan region. We also examined the vocal and morphometric divergence within this complex. Our genetic results suggested that Horornis fortipes is composed of at least three independently evolving lineages, which diverged 1.1-1.8 million years ago. However, these lineages have hardly diverged in song or morphometrics and only very slightly in plumage. Our result indicate that there are three incipient species in Horonis fortipes complex diverged in central Himalayas and Hengduan Mountains, but not between the continent and Taiwan island.}, } @article {pmid30316947, year = {2019}, author = {Galaska, MP and Li, Y and Kocot, KM and Mahon, AR and Halanych, KM}, title = {Conservation of mitochondrial genome arrangements in brittle stars (Echinodermata, Ophiuroidea).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {115-120}, doi = {10.1016/j.ympev.2018.10.002}, pmid = {30316947}, issn = {1095-9513}, abstract = {Brittle stars are conspicuous members of benthic ecosystems, fill many ecological niches and are the most speciose of all classes of echinoderms. With high levels of biodiversity, elucidating the evolutionary history of this group is important. Understanding of higher-level relationships within Ophiuroidea has been aided by multilocus nuclear data and DNA barcoding. However, the degree of consistency between mitochondrial and nuclear data within ophiuroids remains unclear and deserves further assessment. In this study, 17 mitochondrial genomes spanning the taxonomic breadth of Ophiuroidea were utilized to explore evolutionary relationships through maximum likelihood analyses, Bayesian inference and comparative assessment of gene order. Our phylogenetic analyses, based on both nucleotide and amino acid residues, support recent findings based on multilocus nuclear data and morphology, in that the brittle star clades Ophintegrida and Euryophiurida were recovered as monophyletic with the latter comprising Euyalida, Ophiuridae and Ophiopyrgidae. Only three different arrangements of the 13 protein coding and 2 ribosomal RNA genes were observed. As expected, tRNA genes were more likely to have undergone rearrangement but the order of all 37 genes was found to be conserved in all sampled Euryalida and Ophiuridae. Both Euryalida and the clade comprised of Ophiuridae and Ophiopyrgidae, each had their own conserved rearrangement of protein coding genes and ribosomal genes, after divergence from their last common ancestor. Euryalida has a rearrangement of the two ribosomal RNA genes, rrnS and rrnL, in contrast to Ophiuridae and Ophiopyrgidae, which had an inversion of the genes nad1, nad2, and cob relative to Ophintegrida. Further, our data support the gene order found in all sampled Euryalida as the most likely ancestral order for all Ophiuroidea.}, } @article {pmid30316946, year = {2019}, author = {Kise, H and Maeda, T and Reimer, JD}, title = {A phylogeny and the evolution of epizoism within the family Hydrozoanthidae with description of a new genus and two new species.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {304-314}, doi = {10.1016/j.ympev.2018.10.011}, pmid = {30316946}, issn = {1095-9513}, abstract = {The Family Hydrozoanthidae are macrocnemic zoantharians, however their phylogenetic position is closer to brachycnemic zoantharians than to other macrocnemic zoantharians. Previous studies have indicated the presence of undescribed Hydrozoanthidae species from various locations in the Indo-Pacific Ocean. In this study, two new Hydrozoanthidae species, Aenigmanthus segoi gen. n., sp. n. and Hydrozoanthus sils sp. n., are described from Japanese and Palauan waters based on combined morphological and molecular phylogenetic analyses utilizing multiple genetic markers. Additionally, Hydrozoanthidae consists of species with an obligate epizoic relationship with hydroids (Hydrozoanthus) and of species with facultative epizoic relationships (Aenigmanthus gen. n. and Terrazoanthus). Results of ancestral state reconstruction analyses indicate that Hydrozoanthus gained obligate epizoic relationships in their evolutionary history perhaps due to structural differences of host invertebrates.}, } @article {pmid30316580, year = {2018}, author = {Goldstrohm, AC and Hall, TMT and McKenney, KM}, title = {Post-transcriptional Regulatory Functions of Mammalian Pumilio Proteins.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {12}, pages = {972-990}, pmid = {30316580}, issn = {0168-9525}, support = {R01 GM105707/GM/NIGMS NIH HHS/United States ; Z01 ES050165-11/NULL/Intramural NIH HHS/United States ; ZIA ES050165-21/NULL/Intramural NIH HHS/United States ; }, abstract = {Mammalian Pumilio proteins, PUM1 and PUM2, are members of the PUF family of sequence-specific RNA-binding proteins. In this review, we explore their mechanisms, regulatory networks, biological functions, and relevance to diseases. Pumilio proteins bind an extensive network of mRNAs and repress protein expression by inhibiting translation and promoting mRNA decay. Opposingly, in certain contexts, they can activate protein expression. Pumilio proteins also regulate noncoding (nc)RNAs. The ncRNA, ncRNA activated by DNA damage (NORAD), can in turn modulate Pumilio activity. Genetic analysis provides new insights into Pumilio protein function. They are essential for growth and development. They control diverse processes, including stem cell fate, and neurological functions, such as behavior and memory formation. Novel findings show that their dysfunction contributes to neurodegeneration, epilepsy, movement disorders, intellectual disability, infertility, and cancer.}, } @article {pmid30316297, year = {2018}, author = {Jo, Y and Cho, WK}, title = {RNA viromes of the oriental hybrid lily cultivar "Sorbonne".}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {748}, pmid = {30316297}, issn = {1471-2164}, support = {117120-01//Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries/ ; NRF-2018R1D1A1B07043597//National Research Foundation of Korea/ ; }, mesh = {Gene Expression Profiling ; Genome, Viral/genetics ; *Hybridization, Genetic ; Lilium/*virology ; Mutation ; Phylogeny ; Plant Viruses/*genetics ; RNA, Viral/*genetics ; }, abstract = {BACKGROUND: The lily is a perennial flowering plant belonging to the genus Lilium in the family Liliaceae. Most cultivated lily plants are propagated by bulbs. Therefore, numerous lily bulbs are frequently infected by diverse viruses causing viral diseases. To date, no study has examined the viromes of plants of one type with identical genetic backgrounds collected from different geographical regions.

RESULTS: Here, we examined different viromes of the lily cultivar "Sorbonne" using 172 gigabytes of transcriptome data composed of 23 libraries from four different projects for the cultivar "Sorbonne." We identified 396 virus-associated contigs from all but one library. We identified six different viruses, including Plantago asiatica mosaic virus (PlAMV), Cucumber mosaic virus (CMV), Lily symptomless virus (LSV), Tulip virus X (TVX), Lily mottle virus (LMoV), and Tobacco rattle virus (TRV). Of them, PlAMV was the most common virus infecting the lily. Scale and flower samples possessed a high number of virus-associated reads. We assembled 32 nearly complete genomes for the six identified viruses possessing the polyadenylate tails. Genomes of all six viruses were highly conserved in the lily cultivar "Sorbonne" based on mutation analysis. We identified defective RNAs from LSV, TVX, and PlAMV localized in the triple gene block region. Phylogenetic analyses showed that virus genomes are highly correlated with geographical regions and host plants.

CONCLUSIONS: We conducted comprehensive virome analyses of a single lily cultivar, "Sorbonne," using transcriptome data. Our results shed light on an array of lily virome-associated topics, including virus identification, the dominant virus, virus accumulation in different plant tissues, virus genome assembly, virus mutation, identification of defective RNAs, and phylogenetic relationships of identified viruses. Taken together, we provide very useful methods and valuable results that can be applied in other virome-associated studies.}, } @article {pmid30316294, year = {2018}, author = {Wu, S and Zhu, P and Jia, B and Yang, J and Shen, Y and Cai, X and Sun, X and Zhu, Y and Sun, M}, title = {A Glycine soja group S2 bZIP transcription factor GsbZIP67 conferred bicarbonate alkaline tolerance in Medicago sativa.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {234}, pmid = {30316294}, issn = {1471-2229}, support = {31671596//National Natural Science Foundation of China/ ; 31500204//National Natural Science Foundation of China/ ; UNPYSCT-2017105//Program for Young Scholars with Creative Talents in Heilongjiang Province/ ; 2017T100253//China Postdoctoral Science Foundation/ ; 2015M581494//China Postdoctoral Science Foundation/ ; }, mesh = {Alkalies/toxicity ; Amino Acid Sequence ; Basic-Leucine Zipper Transcription Factors/genetics/*metabolism ; Bicarbonates/*toxicity ; Cell Nucleus/metabolism ; *Gene Expression Regulation, Plant ; Genes, Reporter ; Medicago sativa/genetics/*physiology ; Phenotype ; Phylogeny ; Plant Proteins/genetics/metabolism ; Plant Roots/genetics/physiology ; Plant Shoots/genetics/physiology ; Plants, Genetically Modified ; Protein Transport ; Sequence Alignment ; Soybeans/*genetics ; Stress, Physiological ; }, abstract = {BACKGROUND: Even though bicarbonate alkaline stress is a serious threat to crop growth and yields, it attracts much fewer researches than high salinity stress. The basic leucine zipper (bZIP) transcription factors have been well demonstrated to function in diverse abiotic stresses; however, their biological role in alkaline tolerance still remains elusive. In this study, we functionally characterized a bZIP gene from Glycine soja GsbZIP67 in bicarbonate alkaline stress responses.

RESULTS: GsbZIP67 was initially identified as a putative bicarbonate responsive gene, on the basis of previous RNA-seq data of 50 mM NaHCO3-treated Glycine soja roots. GsbZIP67 protein possessed a conserved bZIP domain, and belonged to the group S2 bZIP, which is yet less well-studied. Our studies showed that GsbZIP67 targeted to nucleus in Arabidopsis protoplasts, and displayed transcriptional activation activity in yeast cells. The quantitative real-time PCR analyses unraveled the bicarbonate stress responsive expression and tissue specific expression of GsbZIP67 in wild soybean. Further phenotypic analysis illustrated that GsbZIP67 overexpression in alfalfa promoted plant growth under bicarbonate alkaline stress, as evidenced by longer roots and shoots. Furthermore, GsbZIP67 overexpression also modified the physiological indices of transgenic alfalfa under bicarbonate alkaline stress. In addition, the expression levels of several stress responsive genes were also augmented by GsbZIP67 overexpression.

CONCLUSIONS: Collectively, in this study, we demonstrated that GsbZIP67 acted as a positive regulator of plant tolerance to bicarbonate alkaline stress. These results provide direct genetic evidence of group S2 bZIPs in bicarbonate alkaline stress, and will facilitate further studies concerning the cis-elements and/or downstream genes targeted by GsbZIP67 in stress responses.}, } @article {pmid30315582, year = {2018}, author = {Sun, Y and Abbott, RJ and Lu, Z and Mao, K and Zhang, L and Wang, X and Ru, D and Liu, J}, title = {Reticulate evolution within a spruce (Picea) species complex revealed by population genomic analysis.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2669-2681}, doi = {10.1111/evo.13624}, pmid = {30315582}, issn = {1558-5646}, support = {2017YFC0505203//National Key Research and Development Program/ ; 31590821//National Natural Science Foundation of China/ ; 31670665//National Natural Science Foundation of China/ ; 91731301//National Natural Science Foundation of China/ ; 2014CB954100//National Key Project for Basic Research/ ; //1000 Youth Talents Plan/ ; //CAS "Light of West China" Program/ ; }, abstract = {The role of reticulation in the rapid diversification of organisms is attracting greater attention in evolutionary biology. Evidence of genetic exchange between diverging taxa is reported frequently, although most studies fail to show how hybridization and introgression contribute to the adaptation and differentiation of introgressed taxa. Here, we report a population genomics approach to test the role of hybridization and introgression in the evolution of the Picea likiangensis species complex, which comprises four taxa occurring in the biodiversity hotspot of the Hengduan-Himalayan mountains. Based on 84,793 SNPs detected in transcriptomes of 82 trees collected from 35 localities, we identified 18 hybrids (including backcrosses) distributed within the range boundaries of the four taxa. Coalescent simulations, for each pair of taxa and for all taxa taken together, rejected several tree-like divergence models and supported instead a reticulate evolution model with secondary contacts occurring during Pleistocene glacial cycles after initial divergence in the late Pliocene. Significant gene flow occurred among some taxa after secondary contact according to an analysis based on modified ABBA-BABA statistics that accommodated a rapid diversification scenario. A novel finding was that introgression between certain taxa can contribute to increasing divergence (and possibly reproductive isolation) between those taxa and other taxa within a complex at some loci. These results illuminate the reticulate nature of evolution within the P. likiangensis complex and highlight the value of population genomic data in detecting the effects of introgression in the rapid diversification of related taxa.}, } @article {pmid30315323, year = {2019}, author = {Ding, K and Zhang, C and Li, J and Chen, S and Liao, C and Cheng, X and Yu, C and Yu, Z and Jia, Y}, title = {cAMP Receptor Protein of Salmonella enterica Serovar Typhimurium Modulate Glycolysis in Macrophages to Induce Cell Apoptosis.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {1-6}, doi = {10.1007/s00284-018-1574-1}, pmid = {30315323}, issn = {1432-0991}, abstract = {We studied the role of glycolysis in the mechanism of cAMP receptor protein-induced macrophage cell death of Salmonella enterica serovar Typhimurium (S. Typhimurium). Cell apoptosis, caspase-3, -8, -9 enzyme activity, and pyruvic acid, lactic acid, ATP, and hexokinase (HK) contents were determined after infection of macrophages with S. Typhimurium SL1344 wild-type and a cAMP receptor protein mutant strain. While cell apoptosis, caspase-3, -8, -9 enzyme activity, lactic acid, hexokinase, and ATP levels significantly changed by infection with crp mutants compared to the wild-type strain (P < 0.05). Our data suggest that the cAMP receptor protein of S. Typhimurium can modulate macrophage death by effecting glycolysis levels. This finding may help to elucidate the mechanisms of S. Typhimurium pathogenesis.}, } @article {pmid30315222, year = {2018}, author = {Osuna, CE and Lim, SY and Kublin, JL and Apps, R and Chen, E and Mota, TM and Huang, SH and Ren, Y and Bachtel, ND and Tsibris, AM and Ackerman, ME and Jones, RB and Nixon, DF and Whitney, JB}, title = {Publisher Correction: Evidence that CD32a does not mark the HIV-1 latent reservoir.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {E33}, doi = {10.1038/s41586-018-0611-3}, pmid = {30315222}, issn = {1476-4687}, abstract = {In this Brief Communications Arising Comment, the first three authors (Osuna, Lim and Kublin) should have been listed as equally contributing authors; this has been corrected online.}, } @article {pmid30315216, year = {2018}, author = {Du Toit, A}, title = {Time to split.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {716-717}, doi = {10.1038/s41579-018-0108-y}, pmid = {30315216}, issn = {1740-1534}, } @article {pmid30315215, year = {2018}, author = {Hepp, C and Robb, NC}, title = {Coming together during viral assembly.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {721}, doi = {10.1038/s41579-018-0102-4}, pmid = {30315215}, issn = {1740-1534}, } @article {pmid30315147, year = {2018}, author = {Masse, NY and Grant, GD and Freedman, DJ}, title = {Alleviating catastrophic forgetting using context-dependent gating and synaptic stabilization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10467-E10475}, pmid = {30315147}, issn = {1091-6490}, support = {R01 EY019041/EY/NEI NIH HHS/United States ; R01 MH092927/MH/NIMH NIH HHS/United States ; }, mesh = {Algorithms ; *Machine Learning ; Memory ; *Neural Networks (Computer) ; Task Performance and Analysis ; }, abstract = {Humans and most animals can learn new tasks without forgetting old ones. However, training artificial neural networks (ANNs) on new tasks typically causes them to forget previously learned tasks. This phenomenon is the result of "catastrophic forgetting," in which training an ANN disrupts connection weights that were important for solving previous tasks, degrading task performance. Several recent studies have proposed methods to stabilize connection weights of ANNs that are deemed most important for solving a task, which helps alleviate catastrophic forgetting. Here, drawing inspiration from algorithms that are believed to be implemented in vivo, we propose a complementary method: adding a context-dependent gating signal, such that only sparse, mostly nonoverlapping patterns of units are active for any one task. This method is easy to implement, requires little computational overhead, and allows ANNs to maintain high performance across large numbers of sequentially presented tasks, particularly when combined with weight stabilization. We show that this method works for both feedforward and recurrent network architectures, trained using either supervised or reinforcement-based learning. This suggests that using multiple, complementary methods, akin to what is believed to occur in the brain, can be a highly effective strategy to support continual learning.}, } @article {pmid30314917, year = {2018}, author = {Eisenhauer, N and Herrmann, S and Hines, J and Buscot, F and Siebert, J and Thakur, MP}, title = {The Dark Side of Animal Phenology.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {898-901}, doi = {10.1016/j.tree.2018.09.010}, pmid = {30314917}, issn = {1872-8383}, abstract = {Research exploring the timing of recurring biological events has shown that anthropogenic climate change dramatically alters the phenology of many plants and animals. However, we still lack studies on how climate change might alter the phenology of soil invertebrates as well as how this can subsequently affect ecosystem functions.}, } @article {pmid30314916, year = {2018}, author = {Bálint, M and Pfenninger, M and Grossart, HP and Taberlet, P and Vellend, M and Leibold, MA and Englund, G and Bowler, D}, title = {Environmental DNA Time Series in Ecology.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {945-957}, doi = {10.1016/j.tree.2018.09.003}, pmid = {30314916}, issn = {1872-8383}, abstract = {Ecological communities change in time and space, but long-term dynamics at the century-to-millennia scale are poorly documented due to lack of relevant data sets. Nevertheless, understanding long-term dynamics is important for explaining present-day biodiversity patterns and placing conservation goals in a historical context. Here, we use recent examples and new perspectives to highlight how environmental DNA (eDNA) is starting to provide a powerful new source of temporal data for research questions that have so far been overlooked, by helping to resolve the ecological dynamics of populations, communities, and ecosystems over hundreds to thousands of years. We give examples of hypotheses that may be addressed by temporal eDNA biodiversity data, discuss possible research directions, and outline related challenges.}, } @article {pmid30314915, year = {2018}, author = {Bullock, JM and Bonte, D and Pufal, G and da Silva Carvalho, C and Chapman, DS and García, C and García, D and Matthysen, E and Delgado, MM}, title = {Human-Mediated Dispersal and the Rewiring of Spatial Networks.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {958-970}, doi = {10.1016/j.tree.2018.09.008}, pmid = {30314915}, issn = {1872-8383}, abstract = {Humans fundamentally affect dispersal, directly by transporting individuals and indirectly by altering landscapes and natural vectors. This human-mediated dispersal (HMD) modifies long-distance dispersal, changes dispersal paths, and overall benefits certain species or genotypes while disadvantaging others. HMD is leading to radical changes in the structure and functioning of spatial networks, which are likely to intensify as human activities increase in scope and extent. Here, we provide an overview to guide research into HMD and the resulting rewiring of spatial networks, making predictions about the ecological and evolutionary consequences and how these vary according to spatial scale and the traits of species. Future research should consider HMD holistically, assessing the range of direct and indirect processes to understand the complex impacts on eco-evolutionary dynamics.}, } @article {pmid30314807, year = {2018}, author = {White, MW and Suvorova, ES}, title = {Apicomplexa Cell Cycles: Something Old, Borrowed, Lost, and New: (Trends in Parasitology 34, 759-771; 2018).}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {1012-1013}, doi = {10.1016/j.pt.2018.09.002}, pmid = {30314807}, issn = {1471-5007}, } @article {pmid30314806, year = {2018}, author = {Zimmer, SL}, title = {Revisiting Trypanosome Mitochondrial Genome Mysteries: Broader and Deeper.}, journal = {Trends in parasitology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.pt.2018.09.006}, pmid = {30314806}, issn = {1471-5007}, abstract = {What do the products of a genome do, and when and why are they needed? For the protein products of the trypanosomatid parasites' mitochondrial genomes, the total expressed protein repertoire and the identities of the more difficult-to-characterize products have been challenging to acquire. Comparative genomics and new technologies may resolve that.}, } @article {pmid30314682, year = {2018}, author = {Monteiro, FP}, title = {The "sick dancers": The construction of medical knowledge about the "epidemic of dance" in Itapagipe, Salvador, Bahia (1882-1901).}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {71}, number = {}, pages = {32-40}, doi = {10.1016/j.shpsc.2018.10.005}, pmid = {30314682}, issn = {1879-2499}, mesh = {Brazil/epidemiology ; Chorea/epidemiology/*history/psychology ; Dancing/*history ; *Health Knowledge, Attitudes, Practice ; History, 19th Century ; Humans ; Motor Skills Disorders/epidemiology/*history/psychology ; }, abstract = {The goal of this paper is to analyze a little-known set of documents referring to a "Dancing Epidemic" that took place in Itapagipe, a suburb of Salvador, capital of the province of Bahia, Brazil, in 1882. Through the studies of a group of physicians, especially Raimundo Nina Rodrigues (1862-1906), a psychiatrist and anthropologist from the Bahia School of Medicine, the medical knowledge built on this unique phenomenon in Brazilian history is examined. The case in particular involved a crowd that spread through the streets of Itapagipe, attracting the interest of the medical classes, who were intrigued by the symptoms of motor incoordination the patients manifested. Inspired by foreign literature, but developing their own theories, Rodrigues and colleagues created a unique body of knowledge about the infirmity.}, } @article {pmid30314529, year = {2018}, author = {Khanal, S and Khan, SA and Baral, D and Shrestha, S and Baral, N and Lamsal, M}, title = {Oxidant-antioxidant status and assessment of cardiovascular morbidity in Pan Masala containing Tobacco users: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {727}, pmid = {30314529}, issn = {1756-0500}, mesh = {Adult ; Antioxidants/*metabolism ; Ascorbic Acid/*blood ; Cardiovascular Diseases/*blood/*chemically induced ; Cross-Sectional Studies ; Female ; Humans ; Male ; Malondialdehyde/*blood ; Middle Aged ; Nepal ; Oxidative Stress/*drug effects ; Tobacco, Smokeless/*adverse effects ; Vitamin E/*blood ; }, abstract = {OBJECTIVE: Pan Masala containing Tobacco (PMT) use contributes significantly to the overall world tobacco burden especially in south Asian country like Nepal. Oxidative stress caused by it may leads to cardiovascular disease, peripheral vascular disease, hypertension, etc. Therefore, this work proposes to study the antioxidant and oxidative stress along with cardiovascular morbidity in PMT users.

RESULTS: Hundred PMT users and 80 non-user controls with age and sex matched were enrolled. There was a significant difference in blood pressure, albumin, uric acid, vitamin C, vitamin E, malondialdehyde (MDA), total cholesterol, triglycerides, low density lipoprotein cholesterol between the two groups (p < 0.001). We observed statistically significant (p < 0.001) decrease in antioxidant and increase oxidative stress in PMT users. Duration and quantity of PMT user were significantly associated with the MDA level.}, } @article {pmid30314502, year = {2018}, author = {Vallersnes, OM and Jacobsen, D and Ekeberg, Ø and Brekke, M}, title = {Factors associated with rapidly repeated acute poisoning by substances of abuse: a prospective observational cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {724}, pmid = {30314502}, issn = {1756-0500}, support = {-//The Norwegian Research Fund for General Practice/ ; }, mesh = {Adult ; Analgesics, Opioid/*poisoning ; Emergency Medical Services/*statistics & numerical data ; Ethanol/*poisoning ; Female ; Homeless Persons/*statistics & numerical data ; Humans ; Male ; Norway/epidemiology ; Patient Dropouts/*statistics & numerical data ; Poisoning/*epidemiology ; Primary Health Care/*statistics & numerical data ; Prospective Studies ; Substance-Related Disorders/*epidemiology ; *Suicidal Ideation ; }, abstract = {OBJECTIVE: We have previously found that 9% of patients treated for acute poisoning by substances of abuse in a primary care emergency outpatient setting presented with a new poisoning within a week. We now identify factors associated with rapidly repeated acute poisoning by substances of abuse.

RESULTS: In 169/1952 (9%) cases of acute poisoning by substances of abuse included consecutively from October 2011 through September 2012 at a primary care emergency outpatient clinic in Oslo, Norway, the patient re-presented within a week with a new poisoning. Homeless patients were more likely to re-present, adjusted odds ratio (AOR) 2.0 (95% confidence interval (CI) 1.3-3.2, p = 0.003), as were self-discharging patients, AOR 1.7 (95% CI 1.2-2.4, p = 0.007), and patients with an opioid as main toxic agent, AOR 1.5 (95% CI 1.0-2.3, p = 0.028). There was no statistically significant association between rapid re-presentation and severe mental illness or suicidal intention.}, } @article {pmid30314484, year = {2018}, author = {Sagar, A and LeCover, R and Shoemaker, C and Varner, J}, title = {Dynamic Optimization with Particle Swarms (DOPS): a meta-heuristic for parameter estimation in biochemical models.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {87}, pmid = {30314484}, issn = {1752-0509}, support = {W911NF-10-1-0376//U.S. Army/ ; }, abstract = {BACKGROUND: Mathematical modeling is a powerful tool to analyze, and ultimately design biochemical networks. However, the estimation of the parameters that appear in biochemical models is a significant challenge. Parameter estimation typically involves expensive function evaluations and noisy data, making it difficult to quickly obtain optimal solutions. Further, biochemical models often have many local extrema which further complicates parameter estimation. Toward these challenges, we developed Dynamic Optimization with Particle Swarms (DOPS), a novel hybrid meta-heuristic that combined multi-swarm particle swarm optimization with dynamically dimensioned search (DDS). DOPS uses a multi-swarm particle swarm optimization technique to generate candidate solution vectors, the best of which is then greedily updated using dynamically dimensioned search.

RESULTS: We tested DOPS using classic optimization test functions, biochemical benchmark problems and real-world biochemical models. We performed [Formula: see text] = 25 trials with [Formula: see text] = 4000 function evaluations per trial, and compared the performance of DOPS with other commonly used meta-heuristics such as differential evolution (DE), simulated annealing (SA) and dynamically dimensioned search (DDS). On average, DOPS outperformed other common meta-heuristics on the optimization test functions, benchmark problems and a real-world model of the human coagulation cascade.

CONCLUSIONS: DOPS is a promising meta-heuristic approach for the estimation of biochemical model parameters in relatively few function evaluations. DOPS source code is available for download under a MIT license at http://www.varnerlab.org .}, } @article {pmid30314469, year = {2018}, author = {Colby, SM and McClure, RS and Overall, CC and Renslow, RS and McDermott, JE}, title = {Improving network inference algorithms using resampling methods.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {376}, pmid = {30314469}, issn = {1471-2105}, support = {NA//Biological and Environmental Research/ ; }, mesh = {Algorithms ; Gene Expression/*genetics ; Gene Regulatory Networks/*genetics ; Humans ; }, abstract = {BACKGROUND: Relatively small changes to gene expression data dramatically affect co-expression networks inferred from that data which, in turn, can significantly alter the subsequent biological interpretation. This error propagation is an underappreciated problem that, while hinted at in the literature, has not yet been thoroughly explored. Resampling methods (e.g. bootstrap aggregation, random subspace method) are hypothesized to alleviate variability in network inference methods by minimizing outlier effects and distilling persistent associations in the data. But the efficacy of the approach assumes the generalization from statistical theory holds true in biological network inference applications.

RESULTS: We evaluated the effect of bootstrap aggregation on inferred networks using commonly applied network inference methods in terms of stability, or resilience to perturbations in the underlying expression data, a metric for accuracy, and functional enrichment of edge interactions.

CONCLUSION: Bootstrap aggregation results in improved stability and, depending on the size of the input dataset, a marginal improvement to accuracy assessed by each method's ability to link genes in the same functional pathway.}, } @article {pmid30314467, year = {2018}, author = {Ma, X and Zhao, X and Zhang, Z and Guo, J and Guan, L and Li, J and Mi, M and Huang, Y and Tong, D}, title = {Differentially expressed non-coding RNAs induced by transmissible gastroenteritis virus potentially regulate inflammation and NF-κB pathway in porcine intestinal epithelial cell line.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {747}, pmid = {30314467}, issn = {1471-2164}, support = {Grant No. 31472167//National Natural Science Foundation of China/ ; Grant No. 2015M570860//China Postdoctoral Science Foundation/ ; Grant No. K3360217060//The Central Project of Major Agricultural Technology Promotion Funds/ ; Grant No. 2018ZDXM-NY-064//Key Research and Development Project in Shaanxi Province/ ; Grant No. 2018NY-35//Science and Technology Planning Project of Yangling demonstration zone/ ; }, mesh = {Animals ; Base Sequence ; Cell Line ; *Gene Expression Profiling ; Gene Regulatory Networks ; Inflammation/genetics/virology ; Intestinal Mucosa/*cytology ; NF-kappa B/*metabolism ; RNA, Messenger/genetics ; RNA, Untranslated/*genetics ; Sequence Analysis, RNA ; Swine ; Transmissible gastroenteritis virus/*physiology ; }, abstract = {BACKGROUND: Transmissible gastroenteritis virus (TGEV) infection can activate NF-κB pathway in porcine intestinal epithelial cells and result in severe inflammation. Non-coding RNAs (ncRNAs) are not translated into proteins and play an important role in many biological and pathological processes such as inflammation, viral infection, and mitochondrial damage. However, whether ncRNAs participate in TGEV-induced inflammation in porcine intestinal epithelial cells is largely unknown.

RESULTS: In this study, the next-generation sequencing (NGS) technology was used to analyze the profiles of mRNAs, miRNAs, and circRNAs in Mock- and TGEV-infected intestinal porcine epithelial cell-jejunum 2 (IPEC-J2) cell line. A total of 523 mRNAs, 65 microRNAs (miRNAs), and 123 circular RNAs (circRNAs) were differentially expressed. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis showed differentially expressed mRNAs were linked to inflammation-related pathways, including NF-κB, Toll-like receptor, NOD-like receptor, Jak-STAT, TNF, and RIG-I-like receptor pathways. The interactions among mRNA, miRNA, and circRNA were analyzed. The data showed that ssc_circ_009380 and miR-22 might have interaction relationship. Dual-luciferase reporter assay confirmed that miR-22 directly bound to ssc_circ_009380. We also observed that overexpression of miR-22 led to a reduction of p-IκB-α and accumulation of p65 in nucleus in TGEV-infected IPEC-J2 cells. In contrast, inhibition of miR-22 had the opposite effects. Moreover, silencing of ssc_circ_009380 inhibited accumulation of p65 in nucleus and phosphorylation of IκB-α.

CONCLUSIONS: The data revealed that differentially expressed mRNAs and ncRNAs were primarily enriched in inflammation-related pathways and ssc_circ_009380 promoted activation of NF-κB pathway by binding miR-22 during TGEV-induced inflammation.}, } @article {pmid30314466, year = {2018}, author = {Liu, L and Li, Y and She, G and Zhang, X and Jordan, B and Chen, Q and Zhao, J and Wan, X}, title = {Metabolite profiling and transcriptomic analyses reveal an essential role of UVR8-mediated signal transduction pathway in regulating flavonoid biosynthesis in tea plants (Camellia sinensis) in response to shading.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {233}, pmid = {30314466}, issn = {1471-2229}, support = {31700611//National Natural Science Foundation of China/ ; 1808085QC93//Natural Science Foundation of Anhui Province/ ; 2017B233//Anhui Province Postdoctoral Science Foundation/ ; KJ2017A126//Science Foundation for Anhui Province/ ; }, mesh = {Biosynthetic Pathways ; Caffeine/metabolism ; Camellia sinensis/genetics/*physiology/radiation effects ; Catechin/metabolism ; Chlorophyll/metabolism ; Flavonoids/*metabolism ; Gene Expression Profiling ; Glutamates/metabolism ; Light ; *Metabolome ; Metabolomics ; Plant Leaves/genetics/physiology/radiation effects ; Plant Proteins/genetics/*metabolism ; *Signal Transduction ; Tea ; *Transcriptome ; }, abstract = {BACKGROUND: Tea is the most popular nonalcoholic beverage worldwide for its pleasant characteristics and healthful properties. Catechins, theanine and caffeine are the major natural products in tea buds and leaves that determine tea qualities such as infusion colors, tastes and fragrances, as well as their health benefits. Shading is a traditional and effective practice to modify natural product accumulation and to enhance the tea quality in tea plantation. However, the mechanism underlying the shading effects is not fully understood. This study aims to explore the regulation of flavonoid biosynthesis in Camellia sinensis under shading by using both metabolomic and transcriptional analyses.

RESULTS: While shading enhanced chlorophyll accumulation, major catechins, including C, EC, GC and EGC, decreased significantly in tea buds throughout the whole shading period. The reduction of catechins and flavonols were consistent with the simultaneous down-regulation of biosynthetic genes and TFs associated with flavonoid biosynthesis. Of 16 genes involved in the flavonoid biosynthetic pathway, F3'H and FLS significantly decreased throughout shading while the others (PAL, CHSs, DFR, ANS, ANR and LAR, etc.) temporally decreased in early or late shading stages. Gene co-expression cluster analysis suggested that a number of photoreceptors and potential genes involved in UV-B signal transductions (UVR8_L, HY5, COP1 and RUP1/2) showed decreasing expression patterns consistent with structural genes (F3'H, FLS, ANS, ANR, LAR, DFR and CHSs) and potential TFs (MYB4, MYB12, MYB14 and MYB111) involved in flavonoid biosynthesis, when compared with genes in the UV-A/blue and red/far-red light signal transductions. The KEGG enrichment and matrix correlation analyses also attributed the regulation of catechin biosynthesis to the UVR8-mediated signal transduction pathway. Further UV-B treatment in the controlled environment confirmed UV-B induction on flavonols and EGCG accumulation in tea leaves.

CONCLUSIONS: We proposed that catechin biosynthesis in C. sinensis leaves is predominantly regulated by UV through the UVR8-mediated signal transduction pathway to MYB12/MYB4 downstream effectors, to modulate flavonoid accumulation. Our study provides new insights into our understanding of regulatory mechanisms for shading-enhanced tea quality.}, } @article {pmid30314465, year = {2018}, author = {Xiao, G and Li, B and Chen, H and Chen, W and Wang, Z and Mao, B and Gui, R and Guo, X}, title = {Overexpression of PvCO1, a bamboo CONSTANS-LIKE gene, delays flowering by reducing expression of the FT gene in transgenic Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {232}, pmid = {30314465}, issn = {1471-2229}, support = {30901155//the National Natural Science Foundation of China/ ; }, mesh = {Alleles ; Arabidopsis/genetics/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Bambusa/*genetics ; Cell Nucleus/metabolism ; Circadian Rhythm ; DNA-Binding Proteins/genetics/*metabolism ; Flowers/genetics/physiology ; Gene Expression ; Gene Expression Regulation, Plant ; Multigene Family ; Organ Specificity ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified ; Protein Transport ; Time Factors ; Transcription Factors/genetics/*metabolism ; Two-Hybrid System Techniques ; }, abstract = {BACKGROUND: In Arabidopsis, a long day flowering plant, CONSTANS (CO) acts as a transcriptional activator of flowering under long day (LD) condition. In rice, a short day flowering plant, Hd1, the ortholog of CO, plays dual functions in respond to day-length, activates flowering in short days and represses flowering in long days. In addition, alleles of Hd1 account for ~ 44% of the variation in flowering time observed in cultivated rice and sorghum. How does it work in bamboo? The function of CO in bamboo is similar to that in Arabidopsis?

RESULTS: Two CO homologous genes, PvCO1 and PvCO2, in Phyllostachys violascens were identified. Alignment analysis showed that the two PvCOLs had the highest sequence similarity to rice Hd1. Both PvCO1 and PvCO2 expressed in specific tissues, mainly in leaf. The PvCO1 gene had low expression before flowering, high expression during the flowering stage, and then declined to low expression again after flowering. In contrast, expression of PvCO2 was low during the flowering stage, but rapidly increased to a high level after flowering. The mRNA levels of both PvCOs exhibited a diurnal rhythm. Both PvCO1 and PvCO2 proteins were localized in nucleus of cells. PvCO1 could interact with PvGF14c protein which belonged to 14-3-3 gene family through B-box domain. Overexpression of PvCO1 in Arabidopsis significantly caused late flowering by reducing the expression of AtFT, whereas, transgenic plants overexpressing PvCO2 showed a similar flowering time with WT under LD conditions. Taken together, these results suggested that PvCO1 was involved in the flowering regulation, and PvCO2 may either not have a role in regulating flowering or act redundantly with other flowering regulators in Arabidopsis. Our data also indicated regulatory divergence between PvCOLs in Ph. violascens and CO in Arabidopsis as well as Hd1 in Oryza sativa. Our results will provide useful information for elucidating the regulatory mechanism of COLs involved in the flowering.

CONCLUSIONS: Unlike to the CO gene in Arabidopsis, PvCO1 was a negative regulator of flowering in transgenic Arabidopsis under LD condition. It was likely that long period of vegetative growth of this bamboo species was related with the regulation of PvCO1.}, } @article {pmid30314459, year = {2018}, author = {Aarthy, T and Mulani, FA and Pandreka, A and Kumar, A and Nandikol, SS and Haldar, S and Thulasiram, HV}, title = {Tracing the biosynthetic origin of limonoids and their functional groups through stable isotope labeling and inhibition in neem tree (Azadirachta indica) cell suspension.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {230}, pmid = {30314459}, issn = {1471-2229}, mesh = {Azadirachta/chemistry/*metabolism ; *Biosynthetic Pathways ; Cells, Cultured ; Erythritol/analogs & derivatives ; Isotope Labeling ; Limonins/*biosynthesis/chemistry/metabolism ; Mevalonic Acid/chemistry/*metabolism ; Plant Leaves/chemistry/metabolism ; Seedlings/chemistry/metabolism ; Sugar Phosphates ; Terpenes/chemistry/*metabolism ; }, abstract = {BACKGROUND: Neem tree serves as a cornucopia for triterpenoids called limonoids that are of profound interest to humans due to their diverse biological activities. However, the biosynthetic pathway that plant employs for the production of limonoids remains unexplored for this wonder tree.

RESULTS: Herein, we report the tracing of limonoid biosynthetic pathway through feeding experiments using 13C isotopologues of glucose in neem cell suspension. Growth and development specific limonoid spectrum of neem seedling and time dependent limonoid biosynthetic characteristics of cell lines were established. Further to understand the role of mevalonic acid (MVA) and methylerythritol phosphate (MEP) pathways in limonoid biosynthesis, Ultra Performance Liquid Chromatography (UPLC)- tandem mass spectrometry based structure-fragment relationship developed for limonoids and their isotopologues have been utilized. Analyses of labeled limonoid extract lead to the identification of signature isoprenoid units involved in azadirachtin and other limonoid biosynthesis, which are found to be formed through mevalonate pathway. This was further confirmed by treatment of cell suspension with mevinolin, a specific inhibitor for MVA pathway, which resulted in drastic decrease in limonoid levels whereas their biosynthesis was unaffected with fosmidomycin mediated plastidial methylerythritol 4-phosphate (MEP) pathway inhibition. This was also conspicuous, as the expression level of genes encoding for the rate-limiting enzyme of MVA pathway, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGR) was comparatively higher to that of deoxyxylulose-phosphate synthase (DXS) of MEP pathway in different tissues and also in the in vitro grown cells. Thus, this study will give a comprehensive understanding of limonoid biosynthetic pathway with differential contribution of MVA and MEP pathways.

CONCLUSIONS: Limonoid biosynthesis of neem tree and cell lines have been unraveled through comparative quantification of limonoids with that of neem tree and through 13C limonoid isotopologues analysis. The undifferentiated cell lines of neem suspension produced a spectrum of C-seco limonoids, similar to parental tissue, kernel. Azadirachtin, a C-seco limonoid is produced in young tender leaves of plant whereas in the hard mature leaves of tree, ring intact limonoid nimocinol accumulates in high level. Furthermore, mevalonate pathway exclusively contributes for isoprene units of limonoids as evidenced through stable isotope labeling and no complementation of MEP pathway was observed with mevalonate pathway dysfunction, using chemical inhibitors.}, } @article {pmid30314458, year = {2018}, author = {Melicher, D and Su, KFY and Meier, R and Bowsher, JH}, title = {Comparative analysis reveals the complex role of histoblast nest size in the evolution of novel insect abdominal appendages in Sepsidae (Diptera).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {151}, pmid = {30314458}, issn = {1471-2148}, support = {1210097//National Science Foundation/International ; 0811239//National Science Foundation/International ; R-154-000-A62-112//Ministry of Education - Singapore/International ; }, mesh = {Abdomen/*anatomy & histology ; Animals ; *Biological Evolution ; Body Size ; Cell Count ; Diptera/*anatomy & histology/classification/cytology ; Female ; Larva/anatomy & histology ; Male ; Phylogeny ; Sex Characteristics ; Species Specificity ; }, abstract = {BACKGROUND: The males of some sepsid species (Sepsidae: Diptera) have abdominal appendages that are remarkable in several ways. They are sexually dimorphic, have a complex evolutionary history of gain and loss, and can be jointed and thus highly mobile. The sternite brushes are used extensively in complex courtship behaviors that differ considerably between species and during mating. The abdominal appendages have a novel developmental pathway developing from histoblast nests rather than imaginal discs.

RESULTS: We focus on the evolution of cell number, nest area, and segment length in both sexes to understand how this tissue relates to the formation of novel abdominal appendages. We map histoblast nest size of wandering-phase larvae of 17 species across 10 genera to a phylogenetic tree of Sepsidae and demonstrate that abdominal appendages require significant increases of histoblast nest size and cell number in most species while one species produces small appendages even without such modifications. In species with particularly large appendages, not only the nests on the fourth, but nests in neighboring segments are enlarged (Themira biloba, Themira putris). The loss of abdominal appendages corresponds to the loss of an enlarged fourth histoblast nest, although one species showed an exception to this pattern. One species that constitutes an independent origin of abdominal appendages (Perochaeta dikowi) uses an unusual developmental mechanism in that the histoblast nest sizes are not sexually dimorphic.

CONCLUSIONS: The surprisingly high diversity in histoblast size and degree of sexual dimorphism suggests that the developmental mechanism used for abdominal appendage formation in sepsids is highly adaptable. The presence of appendages usually correlate with increased histoblast cell number and in most cases appendage loss results in a return to ancestral histoblast morphology. However, we also identify several exceptions that indicate the abdominal appendages have a malleable developmental origin that is responsive to selection.}, } @article {pmid30314450, year = {2018}, author = {Song, W and Cao, LJ and Li, BY and Gong, YJ and Hoffmann, AA and Wei, SJ}, title = {Multiple refugia from penultimate glaciations in East Asia demonstrated by phylogeography and ecological modelling of an insect pest.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {152}, pmid = {30314450}, issn = {1471-2148}, support = {31472025//National Natural Science Foundation of China/International ; 6162010//Natural Science Foundation of Beijing Municipality/International ; BZ0432//Beijing Key Laboratory of Environmentally Friendly Pest Management on Northern Fruits/International ; }, mesh = {Animals ; Bayes Theorem ; Discriminant Analysis ; *Ecosystem ; Far East ; Gene Flow ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; *Ice Cover ; Microsatellite Repeats/genetics ; *Models, Theoretical ; Moths/genetics/*physiology ; Multigene Family ; Phylogeny ; *Phylogeography ; Principal Component Analysis ; *Refugium ; }, abstract = {BACKGROUND: Refugial populations in Quaternary glaciations are critical to understanding the evolutionary history and climatic interactions of many extant species. Compared with the well-studied areas of Europe and Northern America, refugia of species in eastern Asia remain largely unknown. Here, we investigated the phylogeographic history of a globally important insect pest, the oriental fruit moth Grapholita molesta, in its native range of China.

RESULTS: Genetic structure analyses unveiled three distinct groups and a set of populations with admixture. Approximate Bayesian Computation (ABC) analyses support range expansion of this moth from southwest groups of Yunnan and Sichuan to northern and eastern China. A set of admixed populations was found around these two ancestral groups. This pattern of genetic structure points to two refugia located in the Yunnan region and Sichuan Basin. The split of the two refugia was dated to 329.2 thousand years ago in the penultimate glacial period. One of the lineages was exclusively found around the Sichuan Basin, indicating the formation of endemic populations in this refugium. Ecological niche model analysis suggested a shrinking distribution from the LIG period to the MID period in the Sichuan lineage but a wide and stable distribution in the other lineage.

CONCLUSIONS: Our results for the first time suggest that Yunnan and Sichuan jointly served as two large-scale refugia in eastern Asia in Quaternary glaciations, helping to maintain genetic diversity overall.}, } @article {pmid30314449, year = {2018}, author = {Shen, E and Zhu, X and Hua, S and Chen, H and Ye, C and Zhou, L and Liu, Q and Zhu, QH and Fan, L and Chen, X}, title = {Genome-wide identification of oil biosynthesis-related long non-coding RNAs in allopolyploid Brassica napus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {745}, pmid = {30314449}, issn = {1471-2164}, support = {2015CB150200//the National Basic Research Program of China/ ; B17039//the 111 Project/ ; }, mesh = {Brassica napus/*genetics/*metabolism ; Conserved Sequence ; Genome, Plant/*genetics ; Genomics ; Plant Oils/*metabolism ; *Polyploidy ; RNA, Long Noncoding/*genetics ; }, abstract = {BACKGROUND: Long noncoding RNAs (lncRNAs) are transcripts longer than 200 bp that do not encode proteins but nonetheless have been shown to play important roles in various biological processes in plants. Brassica napus is an important seed oil crop worldwide and the target of many genetic improvement activities. To understand better the function of lncRNAs in regulating plant metabolic activities, we carried out a genome-wide lncRNA identification of lncRNAs in Brassica napus with a focus on lncRNAs involved in lipid metabolism. Twenty ribosomal RNA depleted strand specific RNA-seq (ssRNA-seq) datasets were generatred using RNAs isolated from B. napus seeds at four developmental stages. For comparison we also included 30 publically available RNA-seq datasets generated from poly(A) enriched mRNAs isolated from from various Brassica napus tissues in our analysis.

RESULTS: A total of 8905 lncRNA loci were identified, including 7100 long intergenic noncoding RNA (lincRNA) loci and 1805 loci generating long noncoding natural antisense transcript (lncNAT). Many lncRNAs were identified only in the ssRNA-seq and poly(A) RNA-seq dataset, suggesting that B. napus has a large lncRNA repertoire and it is necessary to use libraries prepared from different tissues and developmental stages as well as different library preparation approaches to capture the whole spectrum of lncRNAs. Analysis of coexpression networks revealed that among the regulatory modules are networks containing lncRNAs and protein-coding genes related to oil biosynthesis indicating a possible role of lncRNAs in the control of lipid metabolism. One such example is that several lncRNAs are potential regulators of BnaC08g11970D that encodes oleosin1, a protein found in oil bodies and involved in seed lipid accumulation. We also observed that the expression levels of B. napus lncRNAs is positively correlated with their conservation levels.

CONCLUSIONS: We demonstrated that the B. napus genome has a large number of lncRNA and that these lncRNAs are expressed broadly across many developmental times and in different tissue types. We also provide evidence indicating that specific lncRNAs appear to be important regulators of lipid biosynthesis forming regulatory networks with transcripts involved in lipid biosynthesis. We also provide evidence that these lncRNAs are conserved in other species of the Brassicaceae family.}, } @article {pmid30314447, year = {2018}, author = {Bobay, LM and Ochman, H}, title = {Factors driving effective population size and pan-genome evolution in bacteria.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {153}, pmid = {30314447}, issn = {1471-2148}, support = {R35GM118038/NH/NIH HHS/United States ; R01GM108657/NH/NIH HHS/United States ; }, mesh = {Archaea/genetics ; Bacteria/*genetics/growth & development ; *Evolution, Molecular ; Genome Size ; *Genome, Bacterial ; Phylogeny ; Population Density ; Recombination, Genetic/genetics ; }, abstract = {BACKGROUND: Knowledge of population-level processes is essential to understanding the efficacy of selection operating within a species. However, attempts at estimating effective population sizes (Ne) are particularly challenging in bacteria due to their extremely large census populations sizes, varying rates of recombination and arbitrary species boundaries.

RESULTS: In this study, we estimated Ne for 153 species (152 bacteria and one archaeon) defined under a common framework and found that ecological lifestyle and growth rate were major predictors of Ne; and that contrary to theoretical expectations, Ne was unaffected by recombination rate. Additionally, we found that Ne shapes the evolution and diversity of total gene repertoires of prokaryotic species.

CONCLUSION: Together, these results point to a new model of genome architecture evolution in prokaryotes, in which pan-genome sizes, not individual genome sizes, are governed by drift-barrier evolution.}, } @article {pmid30314446, year = {2018}, author = {Penzar, D and Krivozubov, M and Spirin, S}, title = {PQ, a new program for phylogeny reconstruction.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {374}, pmid = {30314446}, issn = {1471-2105}, support = {16-14-10319//Russian Science Foundation/ ; 16-14-10319//Russian Science Foundation/ ; }, mesh = {Algorithms ; *Phylogeny ; Software ; }, abstract = {BACKGROUND: Many algorithms and programs are available for phylogenetic reconstruction of families of proteins. Methods used widely at present use either a number of distance-based principles or character-based principles of maximum parsimony or maximum likelihood.

RESULTS: We developed a novel program, named PQ, for reconstructing protein and nucleic acid phylogenies following a new character-based principle. Being tested on natural sequences PQ improves upon the results of maximum parsimony and maximum likelihood. Working with alignments of 10 and 15 sequences, it also outperforms the FastME program, which is based on one of the distance-based principles. Among all tested programs PQ is proved to be the least susceptible to long branch attraction. FastME outperforms PQ when processing alignments of 45 sequences, however. We confirm a recent result that on natural sequences FastME outperforms maximum parsimony and maximum likelihood. At the same time, both PQ and FastME are inferior to maximum parsimony and maximum likelihood on simulated sequences. PQ is open source and available to the public via an online interface.

CONCLUSIONS: The software we developed offers an open-source alternative for phylogenetic reconstruction for relatively small sets of proteins and nucleic acids, with up to a few tens of sequences.}, } @article {pmid30314445, year = {2018}, author = {Colicchio, JM and Kelly, JK and Hileman, LC}, title = {Parental experience modifies the Mimulus methylome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {746}, pmid = {30314445}, issn = {1471-2164}, support = {IOS-0951254//National Science Foundation/ ; P20-GM103418//Kansas-INBRE/ ; }, mesh = {DNA Methylation ; DNA Transposable Elements/genetics ; *Epigenesis, Genetic ; Gene Expression Profiling ; *Genomics ; Mimulus/*genetics/physiology ; Molecular Sequence Annotation ; Plant Leaves/genetics ; Stress, Physiological/genetics ; }, abstract = {BACKGROUND: Transgenerational plasticity occurs when the environmental experience of an organism modifies the growth and development of its progeny. Leaf damage in Mimulus guttatus exhibits transgenerational plasticity mediated through differential expression of hundreds of genes. The epigenetic mechanisms that facilitate this response have yet to be described.

RESULTS: We performed whole genome bisulfite sequencing in the progeny of genetically identical damaged and control plants and developed a pipeline to compare differences in the mean and variance of methylation between treatment groups. We find that parental damage increases the variability of CG and CHG methylation among progeny, but does not alter the overall mean methylation. Instead it has positive effects in some regions and negative in others. We find 3,396 CHH, 203 CG, and 54 CHG Differentially Methylated Regions (DMRs) ranging from tens to thousands of base pairs scattered across the genome. CHG and CHH DMRs tended to overlap with transposable elements. CG DMRs tended to overlap with gene coding regions, many of which were previously found to be differentially expressed.

CONCLUSIONS: Genome-wide increases in methylome variation suggest that parental conditions can increase epigenetic diversity in response to stress. Additionally, the potential association between CG DMRs and differentially expressed genes supports the hypothesis that differential methylation is a mechanistic component of transgenerational plasticity in M. guttatus.}, } @article {pmid30314444, year = {2018}, author = {Kiba, T}, title = {Novel codons in rat Pdx-1 complementary DNA.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {726}, pmid = {30314444}, issn = {1756-0500}, mesh = {Animals ; *Codon ; *DNA, Complementary ; Female ; *Homeodomain Proteins ; Rats ; Rats, Wistar ; *Trans-Activators ; }, abstract = {OBJECTIVES: Pancreatic and duodenal homeobox-1 (Pdx-1) is a homeodomain-containing transcription factor essential for pancreatic development, beta-cell differentiation and the maintenance of mature beta cell function. To transfect the expression vectors of Pdx-1 in the mammalian cells, the complementary DNA (cDNA) of Pdx-1 was conducted.

RESULTS: Novel codons and amino acids sequences were detected in rat Pdx-1 cDNA. Comparing the previous reports regarding rat Pdx-1 cDNA, 3 novel codons (ACA141CCA, AAG720CCG, GTT742GCT) were detected. The amino acids sequences based on the detected cDNA sequences confirmed those, which were already available in public databases. The present study described novel codons in rat Pdx-1 cDNA. The results may be useful for an effective research against pancreatic development, regeneration or carcinogenesis regarding Pdx-1 expressions.}, } @article {pmid30314443, year = {2018}, author = {Ayele, Y and Melaku, K and Dechasa, M and Ayalew, MB and Horsa, BA}, title = {Assessment of drug related problems among type 2 diabetes mellitus patients with hypertension in Hiwot Fana Specialized University Hospital, Harar, Eastern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {728}, pmid = {30314443}, issn = {1756-0500}, mesh = {Adult ; Antihypertensive Agents/*adverse effects ; Comorbidity ; Diabetes Complications/*drug therapy/epidemiology ; Diabetes Mellitus, Type 2/*drug therapy/epidemiology ; Drug-Related Side Effects and Adverse Reactions/epidemiology/*etiology ; Ethiopia/epidemiology ; Female ; Hospitals, University ; Humans ; Hypertension/*drug therapy/epidemiology ; Hypoglycemic Agents/*adverse effects ; Male ; Middle Aged ; }, abstract = {OBJECTIVE: This study was conducted to assess magnitude and pattern of drug related problems among patients with type 2 diabetes mellitus (T2DM) and hypertension.

RESULTS: This study identified 364 drug related problems (DRPs) across the three categories of drug related problems, giving an average of 1.8 DRPs per patient. The effect of drug treatment being not optimal 179 (49.2%), untreated indication and symptoms 77 (21.1%), unnecessary drug-treatment 39 (10.7%) and adverse drug reactions 69 (19%) were the most frequent categories of DRPs identified. In general, high prevalence of drug-related problems was identified among patients with T2DM hypertension. The effect of drug treatment being not optimal, untreated indication and symptoms, unnecessary drug-treatment and adverse drug reactions were the most frequent categories of drug related problems identified. Therefore, the clinicians should work to improve patient care through prevention and resolving drug related problems since it can affect the quality of the care significantly.}, } @article {pmid30314442, year = {2018}, author = {Almeida, MC and Pina, ES and Hernandes, C and Zingaretti, SM and Taleb-Contini, SH and Salimena, FRG and Slavov, SN and Haddad, SK and França, SC and Pereira, AMS and Bertoni, BW}, title = {Genetic diversity and chemical variability of Lippia spp. (Verbenaceae).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {725}, pmid = {30314442}, issn = {1756-0500}, support = {2011/11756-3//FAPESP/ ; }, mesh = {Brazil ; Genetic Variation/*genetics ; Lippia/*classification/*genetics ; *Phylogeny ; *Phytotherapy ; }, abstract = {BACKGROUND: The genus Lippia comprises 150 species, most of which have interesting medicinal properties. Lippia sidoides (syn. L. origanoides) exhibits strong antimicrobial activity and is included in the phytotherapy program implemented by the Brazilian Ministry of Health. Since species of Lippia are morphologically very similar, conventional taxonomic methods are sometimes insufficient for the unambiguous identification of plant material that is required for the production of certified phytomedicines. Therefore, genetic and chemical analysis with chemotype identification will contribute to a better characterization of Lippia species.

METHODS: Amplified Length Polymorphism and Internal Transcribed Spacer molecular markers were applied to determine the plants' genetic variability, and the chemical variability of Lippia spp. was determined by essential oil composition.

RESULTS: Amplified Length Polymorphism markers were efficient in demonstrating the intra and inter-specific genetic variability of the genus and in separating the species L. alba, L. lupulina and L. origanoides into distinct groups. Phylogenetic analysis using Amplified Length Polymorphism and markers produced similar results and confirmed that L. alba and L. lupulina shared a common ancestor that differ from L. origanoides. Carvacrol, endo-fenchol and thymol were the most relevant chemical descriptors.

CONCLUSION: Based on the phylogenetic analysis it is proposed that L. grata should be grouped within L. origanoides due to its significant genetic similarity. Although Amplified Length Polymorphism and Internal Transcribed Spacer markers enabled the differentiation of individuals, the genotype selection for the production of certified phytomedicines must also consider the chemotype classification that reflects their real medicinal properties.}, } @article {pmid30314441, year = {2018}, author = {Musa, IR and Ali, NI and Elseed, SA and Osman, OE and Adam, I}, title = {Reference intervals of thyroid hormones in Khartoum, Sudan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {729}, pmid = {30314441}, issn = {1756-0500}, mesh = {Adult ; Age Factors ; Aged ; Humans ; Middle Aged ; Radioimmunoassay ; Reference Values ; Sex Factors ; Sudan ; Thyrotropin/*blood ; Thyroxine/*blood ; Triiodothyronine/*blood ; Young Adult ; }, abstract = {OBJECTIVES: This study aimed to establish the reference intervals (RIs) of thyroid function test among the adult Sudanese population in Khartoum, Sudan. A multi-stage survey stratified sampling method was used. Total triiodothyronine (TT3), total thyroxine (TT4) level and thyroid stimulating hormone (TSH) levels were measured using radioimmunoassay gamma counter (Riostad, Germany) to determine the reference intervals.

RESULT: A total of 390 adults aged 20-75 years (male: 40.5%, female: 59.5%) were recruited. The median (95% intervals) serum TSH, TT4 and TT3 levels were 1.2 (0.50-3.1) mIU/L, 103.0 (63.0-159.0) nmol/L and 1.4 (0.8-2.7) nmol/L respectively. Compared with males; females had significantly lower TSH level and significantly higher TT4 level, but there was no significant difference when the TT3 level was assessed. While there was no significant difference in the level of TSH and T3 in the age group, T4 levels have shown a progressive increase with age. In summary the RIs for TSH, TT4 and TT3 in this setting were different from the levels provided by the manufacturers. A significant different was observed in TSH and FT4 when considering gender issue. The RIs were not different in the different age groups except for FT4.}, } @article {pmid30314432, year = {2018}, author = {Glassen, TJ and Oertzen, TV and Konovalov, DA}, title = {Finding the mean in a partition distribution.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {375}, pmid = {30314432}, issn = {1471-2105}, mesh = {Algorithms ; *Bayes Theorem ; Humans ; }, abstract = {BACKGROUND: Bayesian clustering algorithms, in particular those utilizing Dirichlet Processes (DP), return a sample of the posterior distribution of partitions of a set. However, in many applied cases a single clustering solution is desired, requiring a 'best' partition to be created from the posterior sample. It is an open research question which solution should be recommended in which situation. However, one such candidate is the sample mean, defined as the clustering with minimal squared distance to all partitions in the posterior sample, weighted by their probability. In this article, we review an algorithm that approximates this sample mean by using the Hungarian Method to compute the distance between partitions. This algorithm leaves room for further processing acceleration.

RESULTS: We highlight a faster variant of the partition distance reduction that leads to a runtime complexity that is up to two orders of magnitude lower than the standard variant. We suggest two further improvements: The first is deterministic and based on an adapted dynamical version of the Hungarian Algorithm, which achieves another runtime decrease of at least one order of magnitude. The second improvement is theoretical and uses Monte Carlo techniques and the dynamic matrix inverse. Thereby we further reduce the runtime complexity by nearly the square root of one order of magnitude.

CONCLUSIONS: Overall this results in a new mean partition algorithm with an acceleration factor reaching beyond that of the present algorithm by the size of the partitions. The new algorithm is implemented in Java and available on GitHub (Glassen, Mean Partition, 2018).}, } @article {pmid30314430, year = {2018}, author = {Groß, C and de Ridder, D and Reinders, M}, title = {Predicting variant deleteriousness in non-human species: applying the CADD approach in mouse.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {373}, pmid = {30314430}, issn = {1471-2105}, support = {14283//Stichting voor de Technische Wetenschappen/ ; }, mesh = {Animals ; Genetic Variation/*genetics ; Genomics/*methods ; Humans ; Mice ; Molecular Sequence Annotation/*methods ; }, abstract = {BACKGROUND: Predicting the deleteriousness of observed genomic variants has taken a step forward with the introduction of the Combined Annotation Dependent Depletion (CADD) approach, which trains a classifier on the wealth of available human genomic information. This raises the question whether it can be done with less data for non-human species. Here, we investigate the prerequisites to construct a CADD-based model for a non-human species.

RESULTS: Performance of the mouse model is competitive with that of the human CADD model and better than established methods like PhastCons conservation scores and SIFT. Like in the human case, performance varies for different genomic regions and is best for coding regions. We also show the benefits of generating a species-specific model over lifting variants to a different species or applying a generic model. With fewer genomic annotations, performance on the test set as well as on the three validation sets is still good.

CONCLUSIONS: It is feasible to construct species-specific CADD models even when annotations such as epigenetic markers are not available. The minimal requirement for these models is the availability of a set of genomes of closely related species that can be used to infer an ancestor genome and substitution rates for the data generation.}, } @article {pmid30314429, year = {2018}, author = {Farré, P and Heurteau, A and Cuvier, O and Emberly, E}, title = {Dense neural networks for predicting chromatin conformation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {372}, pmid = {30314429}, issn = {1471-2105}, support = {DEQ20160334940//Fondation pour la Recherche Médicale/ ; }, mesh = {Chromatin/*chemistry ; Molecular Conformation ; *Neural Networks (Computer) ; }, abstract = {BACKGROUND: DNA inside eukaryotic cells wraps around histones to form the 11nm chromatin fiber that can further fold into higher-order DNA loops, which may depend on the binding of architectural factors. Predicting how the DNA will fold given a distribution of bound factors, here viewed as a type of sequence, is currently an unsolved problem and several heterogeneous polymer models have shown that many features of the measured structure can be reproduced from simulations. However a model that determines the optimal connection between sequence and structure and that can rapidly assess the effects of varying either one is still lacking.

RESULTS: Here we train a dense neural network to solve for the local folding of chromatin, connecting structure, represented as a contact map, to a sequence of bound chromatin factors. The network includes a convolutional filter that compresses the large number of bound chromatin factors into a single 1D sequence representation that is optimized for predicting structure. We also train a network to solve the inverse problem, namely given only structural information in the form of a contact map, predict the likely sequence of chromatin states that generated it.

CONCLUSIONS: By carrying out sensitivity analysis on both networks, we are able to highlight the importance of chromatin contexts and neighborhoods for regulating long-range contacts, along with critical alterations that affect contact formation. Our analysis shows that the networks have learned physical insights that are informative and intuitive about this complex polymer problem.}, } @article {pmid30312413, year = {2018}, author = {Van Geel, M and Yu, K and Ceulemans, T and Peeters, G and van Acker, K and Geerts, W and Ramos, MA and Serafim, C and Kastendeuch, P and Najjar, G and Ameglio, T and Ngao, J and Saudreau, M and Waud, M and Lievens, B and Castro, PM and Somers, B and Honnay, O}, title = {Variation in ectomycorrhizal fungal communities associated with Silver linden (Tilia tomentosa) within and across urban areas.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy207}, pmid = {30312413}, issn = {1574-6941}, abstract = {Trees in urban areas face harsh environmental conditions. Ectomycorrhizal fungi (EcM) form a symbiosis with many tree species and provide a range of benefits to their host through their extraradical hyphal network. Although our understanding of the environmental drivers and large scale geographical variation of EcM communities in natural ecosystems is growing, our knowledge of EcM communities within and across urban areas is still limited. Here, we characterized EcM communities using Illumina miseq sequencing on 175 root samples of the urban tree Tilia tomentosa from three European cities, namely Leuven (Belgium), Strasbourg (France) and Porto (Portugal). We found strong differences in EcM richness and community composition between cities. Soil acidity, organic matter and moisture content were significantly associated with EcM community composition. In agreement, the explained variability in EcM communities was mostly attributed to general soil characteristics, whereas very little variation was explained by city and heavy metal pollution. Overall, our results suggest that EcM communities in urban areas are significantly associated with soil characteristics, while heavy metal pollution and biogeography had little or no impact. These findings deliver new insights into EcM distribution patterns in urban areas and contribute to specific inoculation strategies to improve urban tree vitality.}, } @article {pmid30311879, year = {2018}, author = {Chen, S and Sun, S and Xu, Y and Liu, HC}, title = {Halococcus salsus sp. nov., a novel halophilic archaeon isolated from rock salt.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3754-3759}, doi = {10.1099/ijsem.0.003051}, pmid = {30311879}, issn = {1466-5034}, mesh = {Base Composition ; Bolivia ; China ; DNA, Archaeal/genetics ; Halococcus/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Organophosphorus Compounds/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Sodium Chloride ; }, abstract = {Two pink-pigmented halophilic archaea, designated strains ZJ1T and J81, were isolated from rock salt of Yunnan Salt Mine, China, and commercial salt imported from Bolivia, respectively. Cells were non-motile, coccoid, approximately 0.8-1.6 µm in diameter, stained Gram-negative and often occurred in pairs. Colonies were wet, opaque and smooth-edged. Strain ZJ1T grew optimally with 20 % (w/v) NaCl, at pH 7.5 and at 38-40 °C, which was the same as for strain J81. 16S rRNA gene sequence similarity between strains ZJ1T and J81 was 99.7 %. Sequence similarity searches based on the 16S rRNA gene and cell morphology suggested that strains ZJ1T and J81 belong to the genus Halococcus in the family Halococcaceae. The major polar lipids of the type strain, ZJ1T, were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and sulfated diglycosyl-diether-1. The profile of polar lipids, cell shape, motility and lack of lysis of cells in distilled water show that strains ZJ1T and J81 were similar to other members of the genus Halococcus. Strain ZJ1T shared the highest 16S rRNA gene and rpoB' gene sequence similarities of 99.0 and 95.3 % with Halococcus hamelinensis 100A6T, respectively, followed by less than 94.6 % with sequences of other species in the genus Halococcus. DNA-DNA relatedness between strains ZJ1T and J81 was 90.1±0.7 %, while 27±0.5 % was found between strain ZJ1T and H. hamelinensis JCM 12892T (=100A6T), and 29.0±0.5 % between strains J81 and H. hamelinensis JCM 12892T. The DNA G+C content of strain ZJ1T was 66.5 mol% (Tm). The stable phylogenetic position, differential physiological and biochemical properties and extensive sequence divergence suggest that strains ZJ1T and J81 represent a novel species, for which the name Halococcus salsus sp. nov. is proposed. The type strain is ZJ1T (=CGMCC 1.16025T=NBRC 112867T).}, } @article {pmid30311876, year = {2018}, author = {Kim, BJ and Kim, BR and Jeong, J and Lim, JH and Park, SH and Lee, SH and Kim, CK and Kook, YH and Kim, BJ}, title = {A description of Mycobacterium chelonae subsp. gwanakae subsp. nov., a rapidly growing mycobacterium with a smooth colony phenotype due to glycopeptidolipids.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3772-3780}, doi = {10.1099/ijsem.0.003056}, pmid = {30311876}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Humans ; Multilocus Sequence Typing ; Mycobacterium Infections/microbiology ; Mycobacterium chelonae/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Sputum/*microbiology ; }, abstract = {Three rapidly growing mycobacterial strains, MOTTH4W, MOTT36WT and MOTT68W, were isolated from the sputa of three independent Korean patients co-infected with Mycobacterium yongonense Type II strains. The 16S rRNA gene sequences of all three strains were unique, which were closest to that of Mycobacterium chelonae subsp. bovis KCTC 39630T (99.9 % similarity). Multilocus sequence typing analysis targeting 10 housekeeping genes including hsp65 and rpoB revealed the distinct phylogenetic location of these strains, which were clustered with M. chelonae subsp. chelonae ATCC 35752T and M. chelonae subsp. bovis KCTC 39630T. Phylogenetic analysis based on whole genome sequences revealed a 95.89 % average nucleotide identity (ANI) value with M. chelonae subsp. chelonae, slightly higher than the 95.0 % ANI criterion for determining a novel species. In addition, phenotypic characteristics such as a smooth colony morphology and growth inhibition at 37 °C, distinct MALDI-TOF MS profiles of extracted total lipids due to surface glycopeptidolipids, and distinct drug susceptibility profiles further supported the taxonomic characterization of these strains as representing a novel subspecies of Mycobacterium chelonae. Mycobacterium chelonae subsp. gwanakae subsp. nov. is proposed and the type strain is MOTT36WT (=KCTC 29127T=JCM 32454T).}, } @article {pmid30311869, year = {2018}, author = {Song, Z and Sun, QW and Liang, LX and Zhang, XX and Li, LB and Liu, L}, title = {Zobellella endophytica sp. nov., isolated from the roots of Phragmites communis in the Kumtag Desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3807-3811}, doi = {10.1099/ijsem.0.003064}, pmid = {30311869}, issn = {1466-5034}, mesh = {Aeromonadaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Desert Climate ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; Poaceae/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-negative, aerobic, non-spore-forming, rod-shaped, motile bacterium, named strain 59N8T, was isolated from Phragmites communis roots in the Kumtag Desert. Phylogenetic analysis based on the 16S rRNA gene sequence showed that the isolate belongs to the genus Zobellella within the family Aeromonadaceae. The analysis showed that strain 59N8T was most closely related to Zobellella taiwanensis ZT1T. The average nucleotide identity value with Zobellella taiwanensis ZT1T was 88.2 %, and the digital DNA-DNA hybridization value was 29.7±2.4 %, which was calculated using the Genome-to-Genome Distance Calculator. The G+C content of strain 59N8T was 62.8 mol%. Strain 59N8T grew at 0-5 % (w/v) NaCl (optimum, 0-4 %), pH 6.0-9.0 (optimum, 7.0-8.0) and at 10-45 °C. The major cellular fatty acids were summed feature 8 (C18 : 1ω7c/C18 : 1ω6c), summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) and C16 : 0. The major polar lipids in strain 59N8T were phosphatidylethanolamine and phosphatidylglycerol. Based on the chemotaxonomic, phylogenetic and phenotypic data, strain 59N8T represents a novel species in the genus Zobellella, for which the name Zobellellaendophytica sp. nov. is proposed. The type strain is 59N8T (=ACCC 60074T=KCTC 62456T).}, } @article {pmid30311711, year = {2019}, author = {Richardson, J and Smiseth, PT}, title = {Effects of variation in resource acquisition during different stages of the life cycle on life-history traits and trade-offs in a burying beetle.}, journal = {Journal of evolutionary biology}, volume = {32}, number = {1}, pages = {19-30}, doi = {10.1111/jeb.13388}, pmid = {30311711}, issn = {1420-9101}, support = {NE/L002558/1//Natural Environment Research Council/ ; }, abstract = {Individual variation in resource acquisition should have consequences for life-history traits and trade-offs between them because such variation determines how many resources can be allocated to different life-history functions, such as growth, survival and reproduction. Since resource acquisition can vary across an individual's life cycle, the consequences for life-history traits and trade-offs may depend on when during the life cycle resources are limited. We tested for differential and/or interactive effects of variation in resource acquisition in the burying beetle Nicrophorus vespilloides. We designed an experiment in which individuals acquired high or low amounts of resources across three stages of the life cycle: larval development, prior to breeding and the onset of breeding in a fully crossed design. Resource acquisition during larval development and prior to breeding affected egg size and offspring survival, respectively. Meanwhile, resource acquisition at the onset of breeding affected size and number of both eggs and offspring. In addition, there were interactive effects between resource acquisition at different stages on egg size and offspring survival. However, only when females acquired few resources at the onset of breeding was there evidence for a trade-off between offspring size and number. Our results demonstrate that individual variation in resource acquisition during different stages of the life cycle has important consequences for life-history traits but limited effects on trade-offs. This suggests that in species that acquire a fixed-sized resource at the onset of breeding, the size of this resource has larger effects on life-history trade-offs than resources acquired at earlier stages.}, } @article {pmid30311708, year = {2018}, author = {Sandre, SL and Kaart, T and Morehouse, N and Tammaru, T}, title = {Weak and inconsistent associations between melanic darkness and fitness-related traits in an insect.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1959-1968}, doi = {10.1111/jeb.13387}, pmid = {30311708}, issn = {1420-9101}, support = {IUT20-33//Estonian Ministry of Education and Research/ ; }, abstract = {The idea that the fitness value of body coloration may be affected by biochemically mediated trade-offs has received much research attention. For example, melanization is believed to interact with other fitness-related traits via competition for substrates, costs associated with the synthesis of melanin or pleiotropic effects of the involved genes. However, genetic correlations between coloration and fitness-related traits remain poorly understood. Here, we present a quantitative-genetic study of a coloration trait correlated to melanin-based cuticular darkness ('darkness', hereafter) in a geometrid moth, Ematurga atomaria. This species has considerable variation in larval appearance. We focus on correlations between larval darkness and fitness-related growth performance traits. Both a half-sib analysis and an 'animal model' approach revealed moderately high heritabilities of larval darkness and indices of growth performance. Heritability estimates of darkness derived from the animal model were, however, considerably higher than those based on the half-sib model suggesting that the determination of coloration includes genetic interactions and epigenetic effects. Importantly, on the host plant with the largest sample size, we found no evidence for either genetic or environmental correlations between darkness and growth parameters. On an alternative host plant, there was some indication of positive genetic and negative environmental correlation between these traits. This shows that respective relationships are environment-specific. Nevertheless, the overall pattern of weak and inconsistent correlations between larval coloration and growth parameters does not support universal trade-offs between these traits and suggests that physiological costs of producing colour patterns do not necessarily interfere with adaptive evolution of coloration.}, } @article {pmid30311625, year = {2018}, author = {Nawaz, A and Mäkinen, A and Pärnänen, P and Meurman, JH}, title = {Proteolytic activity of non-albicans Candida and Candida albicans in oral cancer patients.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {296-301}, pmid = {30311625}, issn = {1121-7138}, abstract = {Oral Candida infections can be life-threatening in medically compromised patients. In particular non-albicans Candida strains are virulent. However, our knowledge is sparse on how proteolytic these strains are in patients with oral cancer. Our study aimed to investigate differences in proteolytic activity of non-albicans Candida and Candida albicans isolated from oral cancer patients. The hypothesis was based on anticipated different invasive capacity of the strains. Clinical and reference yeast samples from our laboratory were used for analyses. Candida strains were grown in yeast peptone glucose and the activity of Candida proteinases of broken cell fractions were analysed by MDPF-gelatin zymography. Fluorometric assay was used to compare activities of proteolytic enzymes and degradation assays were performed using CLDN 4 and plasma fibronectin. Clear differences were seen in the proteolytic activity between the studied non-albicans Candida and C. albicans strains. C. tropicalis had the highest proteolytic activity followed by strains of C. krusei and C. glabrata. The results confirmed our study hypothesis by showing differences between the non-albicans Candida and Candida albicans strains studied. Higher proteolytic activity may thus have an effect on the virulence of non-albicans Candida strains in oral cancer patients.}, } @article {pmid30311624, year = {2018}, author = {Loïez, C and Wallet, F}, title = {Is the Unyvero i60 ITI multiplex PCR system a promising test in the diagnosis of infective endocarditis from heart valves?.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {291-295}, pmid = {30311624}, issn = {1121-7138}, abstract = {The aim of this study was to evaluate the new commercial Unyvero i60 ITI multiplex PCR system (Curetis, Holzgerlingen, Germany) on native cardiac valves in comparison with made in-house 16S rRNA PCR amplification (91E/13BS primers) and conventional microbiological techniques. Forty-four patients (30 men, 14 women) with suspected infective endocarditis (IE) were included in this evaluation corresponding to 30 aortic valves and 14 mitral valves. IE was definite for 40 patients using the modified Duke criteria. 16S rRNA PCR amplification was successful in 22 patients (55%). The Unyvero i60 ITI cartridge yielded a positive result in 16 patients (40%). Among the 40 cases, the etiological agent was not included in the panel of Unyvero i60 ITI cartridge for 14 cases. Moreover, for S. aureus, the Unyvero i60 ITI cartridge quickly yielded the susceptibility to meticillin. The result of the experiment was available after 5 hours whereas 16S rRNA PCR amplification-sequencing needs 14 hours of manipulation. If the manufacturer incorporates new targets able to detect more endocarditis agents such as viridans streptococci, the Unyvero i60 ITI cartridge may be a promising and easy-to-use test.}, } @article {pmid30311623, year = {2018}, author = {Lanzafame, M and Nicole, S and Rizzardo, S and Piacentini, D and Chiesi, S and Lattuada, E and Diani, E and Carelli, M and Vento, S and Gibellini, D}, title = {Immunovirological outcome and HIV-1 DNA decay in a small cohort of HIV-1-infected patients deintensificated from Abacavir/Lamivudine/Dolutegravir to Lamivudine plus Dolutegravir.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {262-267}, pmid = {30311623}, issn = {1121-7138}, abstract = {Combination abacavir/lamivudine/dolutegravir (ABC/3TC/DTG) is approved as a first-line treatment for antiretroviral naïve patients. This report investigated the immunovirological outcome and total HIV-1 DNA decay in a small cohort of naïve HIV-1-positive patients treated with this regimen. In the presence of viral suppression and increased lymphocyte T CD4+ cells, the quantitative analysis of total HIV-1 DNA content revealed a significant decay after 12 months of treatment. Subsequently, we deintensificated the treatment of these patients from (ABC/3TC/DTG) to lamivudine plus dolutegravir (3TC/DTG) after 12 months of virological suppression, as a strategy of "induction-maintenance" therapy. The analysis of HIV-1 RNA viral load, total HIV-1 DNA, CD4+ T lymphocyte count and CD8+ HLA-DR+ T lymphocyte percentage after a mean 3.5 months of therapy deintensification showed no significant difference with respect to data detected after 12 months of ABC/3TC/DTG treatment in the presence of continuous viral suppression. These results indicate that the deintensification of highly active antiretroviral therapy (HAART) from ABC/ 3TC/DTG to 3TC/DTG effectively controls HIV-1 replication and in the early period does not induce any significant variations of total HIV-1 DNA. This suggests that HAART deintensification might be proposed as a therapeutic evolution in the treatment of HIV-1 infection.}, } @article {pmid30311622, year = {2018}, author = {Cama, BAV and Ceccarelli, M and Venanzi Rullo, E and Ferraiolo, F and Paolucci, IA and Maranto, D and Mondello, P and Lo Presti Costantino, MR and Marano, F and D'Andrea, G and Di Marco, V and Puglisi, G and Valenzise, M and D'Angelo, G and Mondello, L and Strano, G and Condorelli, F and Spicola, D and Nunnari, G and Pellicanò, GF}, title = {Outbreak of Brucella melitensis infection in Eastern Sicily: risk factors, clinical characteristics and complication rate.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {}, pmid = {30311622}, issn = {1121-7138}, abstract = {Brucellosis is one of the most common zoonoses in the world, especially in Southern Italy, where many cases are still recorded every year. 128 cases of brucellosis were observed in Messina (Sicily) in 2016, representing a tenfold increase in the number of cases of brucellosis expected. The aim of this multicenter retrospective study was to analyze clinical and microbiological aspects of a brucellosis outbreak in the province of Messina in 2016, the incidence of its complications and the treatment combinations applied. The principal transmission route was through the ingestion of unpasteurized fresh cheese. The mean latency period between the onset of the symptoms and diagnosis was 35.58 ± 42.75 days. A late diagnosis increases the risk of developing complications. Drug-resistant strains of B. melitensis to Trimethoprim/Sulfamethoxazole and Ciprofloxacin were found in blood cultures of 58.4% patients. Brucellosis is still present in Sicily. A diagnostic delay predisposes to complications requiring prolonged therapies. The finding of Brucella melitensis strains resistant to the most widespread treatments is worrisome and needs further investigation. Moreover, the use of alternative combination antibiotic therapy is recommended.}, } @article {pmid30310969, year = {2019}, author = {Jia, T and Wang, RH and Chai, BF}, title = {Various Phyllosphere and Soil Bacterial Communities of Natural Grasses and the Impact Factors in a Copper Tailings Dam.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {7-14}, doi = {10.1007/s00284-018-1575-0}, pmid = {30310969}, issn = {1432-0991}, support = {31600308//National Natural Science Foundation of China/ ; 2016-006//Shanxi Scholarship Council of China/ ; 201601D021101//Shanxi Province Science Foundation for Youths/ ; }, abstract = {Copper mining caused severe damage to the ecological environment of mining areas. The combination of microbe and plant remediation has an application potential in improving the absorption and transformation efficiency of heavy metals. The phyllosphere is the largest biointerface on the planet, and bacteria are the dominant microbial inhabitants of the phyllosphere, believed to be critical to plant growth and health. This study investigated the phyllospheric and soil bacteria communities using high-throughput sequencing, and endophyte infection statuses of four natural grasses by toluidine blue heparin assay. Results showed variation in phyllospheric bacterial community structure. Gammaproteobacteria were the most abundant bacterial population. Bacilli were found in the phyllosphere of Bothriochloa ischaemum and Imperata cylindrica, while Clostridia were only found in Calamagrostis epigejos. Alphaproteobacteria were the dominant bacteria in soil. In addition, bacterial communities were influenced by endophytic infection statuses. Oxalobacteraceae was associated with soil carbon and sulfur. Enterobacteriaceae had negative correlation with the ratio of soil carbon and nitrogen, and had positive correlation with Cd content. These results offer useful insights into phyllospheric bacterial community variance in four different natural grasses in a copper tailings dam.}, } @article {pmid30310968, year = {2019}, author = {Markantonatou, AM and Samaras, K and Yannaki, E and Zachrou, E and Vyzantiadis, TA}, title = {Aspergillus galactomannan detection: Trichoderma as a cause of positive results.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {48-51}, doi = {10.1007/s00284-018-1582-1}, pmid = {30310968}, issn = {1432-0991}, abstract = {Aspergillus galactomannan immunoassay is a main diagnostic and monitoring tool in medical mycology. However, the specificity of the method can be skewered by the presence of several other fungi. Trying to diagnose a possible fungal infection of the lower respiratory tract in a haematology patient, it appeared that the fungus Trichoderma longibrachiatum is an additional probable cause of positive galactomannan results. Although, that Trichoderma is a rare but emerging pathogen in immunocompromised patients, the above information could be a caution point in the clinical evaluation of diagnostic results.}, } @article {pmid30309964, year = {2018}, author = {Liu, P and Rojo de la Vega, M and Sammani, S and Mascarenhas, JB and Kerins, M and Dodson, M and Sun, X and Wang, T and Ooi, A and Garcia, JGN and Zhang, DD}, title = {RPA1 binding to NRF2 switches ARE-dependent transcriptional activation to ARE-NRE-dependent repression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10352-E10361}, pmid = {30309964}, issn = {1091-6490}, support = {P01 HL134610/HL/NHLBI NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; P42 ES004940/ES/NIEHS NIH HHS/United States ; R01 DK109555/DK/NIDDK NIH HHS/United States ; R01 ES026845/ES/NIEHS NIH HHS/United States ; R01 HL125615/HL/NHLBI NIH HHS/United States ; P01 HL126609/HL/NHLBI NIH HHS/United States ; R01 HL091889/HL/NHLBI NIH HHS/United States ; }, mesh = {A549 Cells ; Animals ; Cell Line ; Cell Line, Tumor ; DNA-Binding Proteins/genetics ; Genome/genetics ; Humans ; Mice ; NF-E2-Related Factor 2/*genetics ; Promoter Regions, Genetic/genetics ; Replication Protein A/*genetics ; Repressor Proteins/*genetics ; Response Elements/genetics ; Transcription, Genetic/*genetics ; Transcriptional Activation/*genetics ; }, abstract = {NRF2 regulates cellular redox homeostasis, metabolic balance, and proteostasis by forming a dimer with small musculoaponeurotic fibrosarcoma proteins (sMAFs) and binding to antioxidant response elements (AREs) to activate target gene transcription. In contrast, NRF2-ARE-dependent transcriptional repression is unreported. Here, we describe NRF2-mediated gene repression via a specific seven-nucleotide sequence flanking the ARE, which we term the NRF2-replication protein A1 (RPA1) element (NRE). Mechanistically, RPA1 competes with sMAF for NRF2 binding, followed by interaction of NRF2-RPA1 with the ARE-NRE and eduction of promoter activity. Genome-wide in silico and RNA-seq analyses revealed this NRF2-RPA1-ARE-NRE complex mediates negative regulation of many genes with diverse functions, indicating that this mechanism is a fundamental cellular process. Notably, repression of MYLK, which encodes the nonmuscle myosin light chain kinase, by the NRF2-RPA1-ARE-NRE complex disrupts vascular integrity in preclinical inflammatory lung injury models, illustrating the translational significance of NRF2-mediated transcriptional repression. Our findings reveal a gene-suppressive function of NRF2 and a subset of negatively regulated NRF2 target genes, underscoring the broad impact of NRF2 in physiological and pathological settings.}, } @article {pmid30309963, year = {2018}, author = {Armon, S and Bull, MS and Aranda-Diaz, A and Prakash, M}, title = {Ultrafast epithelial contractions provide insights into contraction speed limits and tissue integrity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10333-E10341}, pmid = {30309963}, issn = {1091-6490}, mesh = {Actins/metabolism ; Animals ; Aquatic Organisms/metabolism/*physiology ; Cells, Cultured ; Epithelial Cells/metabolism/*physiology ; Epithelium/metabolism/*physiology ; Myosins/metabolism ; Placozoa/metabolism/*physiology ; }, abstract = {By definition of multicellularity, all animals need to keep their cells attached and intact, despite internal and external forces. Cohesion between epithelial cells provides this key feature. To better understand fundamental limits of this cohesion, we study the epithelium mechanics of an ultrathin (∼25 μm) primitive marine animal Trichoplax adhaerens, composed essentially of two flat epithelial layers. With no known extracellular matrix and no nerves or muscles, T. adhaerens has been claimed to be the "simplest known living animal," yet is still capable of coordinated locomotion and behavior. Here we report the discovery of the fastest epithelial cellular contractions known in any metazoan, to be found in T. adhaerens dorsal epithelium (50% shrinkage of apical cell area within one second, at least an order of magnitude faster than other known examples). Live imaging reveals emergent contractile patterns that are mostly sporadic single-cell events, but also include propagating contraction waves across the tissue. We show that cell contraction speed can be explained by current models of nonmuscle actin-myosin bundles without load, while the tissue architecture and unique mechanical properties are softening the tissue, minimizing the load on a contracting cell. We propose a hypothesis, in which the physiological role of the contraction dynamics is to resist external stresses while avoiding tissue rupture ("active cohesion"), a concept that can be further applied to engineering of active materials.}, } @article {pmid30309962, year = {2018}, author = {Pandey, V and Wang, B and Mohan, CD and Raquib, AR and Rangappa, S and Srinivasa, V and Fuchs, JE and Girish, KS and Zhu, T and Bender, A and Ma, L and Yin, Z and Basappa, and Rangappa, KS and Lobie, PE}, title = {Discovery of a small-molecule inhibitor of specific serine residue BAD phosphorylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10505-E10514}, pmid = {30309962}, issn = {1091-6490}, mesh = {Antineoplastic Agents/chemistry/*pharmacology ; Apoptosis ; Benzamides/chemistry/*pharmacology ; Cell Proliferation ; Cell Survival/*drug effects ; Databases, Factual ; Drug Delivery Systems ; Drug Discovery ; Humans ; MCF-7 Cells ; Phosphorylation ; Piperazines/chemistry/*pharmacology ; RNA Interference ; Serine/*chemistry ; Small Molecule Libraries ; Surface Plasmon Resonance ; bcl-Associated Death Protein/*antagonists & inhibitors ; }, abstract = {Human BCL-2-associated death promoter (hBAD) is an apoptosis-regulatory protein mediating survival signals to carcinoma cells upon phosphorylation of Ser99, among other residues. Herein, we screened multiple small-molecule databases queried in a Laplacian-modified naive Bayesian-based cheminformatics platform and identified a Petasis reaction product as a site-specific inhibitor for hBAD phosphorylation. Based on apoptotic efficacy against mammary carcinoma cells, N-cyclopentyl-3-((4-(2,3-dichlorophenyl) piperazin-1-yl) (2-hydroxyphenyl) methyl) benzamide (NPB) was identified as a potential lead compound. In vitro biochemical analyses demonstrated that NPB inhibited the phosphorylation of hBAD specifically on Ser99. NPB was observed to exert this effect independently of AKT and other kinase activities despite the demonstration of AKT-mediated BAD-Ser99 phosphorylation. Using a structure-based bioinformatics platform, we observed that NPB exhibited predicted interactions with hBAD in silico and verified the same by direct binding kinetics. NPB reduced phosphorylation of BAD-Ser99 and enhanced caspase 3/7 activity with associated loss of cell viability in various human cancer cell lines derived from mammary, endometrial, ovarian, hepatocellular, colon, prostatic, and pancreatic carcinoma. Furthermore, by use of a xenograft model, it was observed that NPB, as a single agent, markedly diminished BAD phosphorylation in tumor tissue and significantly inhibited tumor growth. Similar doses of NPB utilized in acute toxicity studies in mice did not exhibit significant effects. Hence, we report a site-specific inhibitor of BAD phosphorylation with efficacy in tumor models.}, } @article {pmid30309961, year = {2018}, author = {Du, B and Zielinski, DC and Monk, JM and Palsson, BO}, title = {Thermodynamic favorability and pathway yield as evolutionary tradeoffs in biosynthetic pathway choice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11339-11344}, pmid = {30309961}, issn = {1091-6490}, mesh = {Biological Evolution ; Biomass ; Biosynthetic Pathways/*genetics ; Databases, Genetic ; Genome/genetics ; Metabolic Networks and Pathways/genetics ; Phylogeny ; Thermodynamics ; }, abstract = {The structure of the metabolic network contains myriad organism-specific variations across the tree of life, but the selection basis for pathway choices in different organisms is not well understood. Here, we examined the metabolic capabilities with respect to cofactor use and pathway thermodynamics of all sequenced organisms in the Kyoto Encyclopedia of Genes and Genomes Database. We found that (i) many biomass precursors have alternate synthesis routes that vary substantially in thermodynamic favorability and energy cost, creating tradeoffs that may be subject to selection pressure; (ii) alternative pathways in amino acid synthesis are characteristically distinguished by the use of biosynthetically unnecessary acyl-CoA cleavage; (iii) distinct choices preferring thermodynamic-favorable or cofactor-use-efficient pathways exist widely among organisms; (iv) cofactor-use-efficient pathways tend to have a greater yield advantage under anaerobic conditions specifically; and (v) lysine biosynthesis in particular exhibits temperature-dependent thermodynamics and corresponding differential pathway choice by thermophiles. These findings present a view on the evolution of metabolic network structure that highlights a key role of pathway thermodynamics and cofactor use in determining organism pathway choices.}, } @article {pmid30309960, year = {2018}, author = {Pająk, G and Longa, L and Chrzanowska, A}, title = {Nematic twist-bend phase in an external field.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10303-E10312}, pmid = {30309960}, issn = {1091-6490}, abstract = {The response of the nematic twist-bend ([Formula: see text]) phase to an applied field can provide important insight into the structure of this liquid and may bring us closer to understanding mechanisms generating mirror symmetry breaking in a fluid of achiral molecules. Here we investigate theoretically how an external uniform field can affect structural properties and the stability of [Formula: see text] Assuming that the driving force responsible for the formation of this phase is packing entropy, we show, within Landau-de Gennes theory, that [Formula: see text] can undergo a rich sequence of structural changes with the field. For the systems with positive anisotropy of permittivity, we first observe a decrease of the tilt angle of [Formula: see text] until it transforms through a field-induced phase transition to the ordinary prolate uniaxial nematic phase (N). Then, at very high fields, this nematic phase develops polarization perpendicular to the field ([Formula: see text]). For systems with negative anisotropy of permittivity, the results reveal new modulated structures. Even an infinitesimally small field transforms [Formula: see text] to its elliptical counterpart ([Formula: see text]), where the circular base of the cone of the main director becomes elliptic. With stronger fields, the ellipse degenerates to a line, giving rise to a nonchiral periodic structure, the nematic splay-bend ([Formula: see text]), where the two nematic directors are restricted to a plane. The three structures-[Formula: see text], [Formula: see text], and [Formula: see text]-with a modulated polar order are globally nonpolar. But further increase of the field induces phase transitions into globally polar structures with nonvanishing polarization along the field's direction. We found two such structures, one of which is a polar and chiral modification of [Formula: see text], where splay and bend deformations are accompanied by weak twist deformations ([Formula: see text]). Further increase of the field unwinds this structure into a polar nematic ([Formula: see text]) of polarization parallel to the field.}, } @article {pmid30309959, year = {2018}, author = {Palmer, CM and Alper, HS}, title = {Navigating genetic diversity by painting the bacteria red.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10824-10826}, pmid = {30309959}, issn = {1091-6490}, mesh = {Bacteria/genetics ; Chromosome Painting ; *Genetic Variation ; *Paintings ; }, } @article {pmid30309958, year = {2018}, author = {Dunlop, K and Liston, C}, title = {Stress response regulation and the hemodynamic response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10827-10829}, pmid = {30309958}, issn = {1091-6490}, support = {R01 MH109685/MH/NIMH NIH HHS/United States ; }, mesh = {*Blood Pressure ; *Hemodynamics ; Stress, Psychological ; }, } @article {pmid30309955, year = {2018}, author = {Nikolaeva, S}, title = {A normal student parent.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {258}, doi = {10.1126/science.362.6411.258}, pmid = {30309955}, issn = {1095-9203}, } @article {pmid30309954, year = {2018}, author = {Wei, DS and van der Sar, T and Lee, SH and Watanabe, K and Taniguchi, T and Halperin, BI and Yacoby, A}, title = {Electrical generation and detection of spin waves in a quantum Hall ferromagnet.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {229-233}, doi = {10.1126/science.aar4061}, pmid = {30309954}, issn = {1095-9203}, abstract = {Spin waves are collective excitations of magnetic systems. An attractive setting for studying long-lived spin-wave physics is the quantum Hall (QH) ferromagnet, which forms spontaneously in clean two-dimensional electron systems at low temperature and in a perpendicular magnetic field. We used out-of-equilibrium occupation of QH edge channels in graphene to excite and detect spin waves in magnetically ordered QH states. Our experiments provide direct evidence for long-distance spin-wave propagation through different ferromagnetic phases in the N = 0 Landau level, as well as across the insulating canted antiferromagnetic phase. Our results will enable experimental investigation of the fundamental magnetic properties of these exotic two-dimensional electron systems.}, } @article {pmid30309953, year = {2018}, author = {Wang, L and Lear, JM and Rafferty, SM and Fosu, SC and Nagib, DA}, title = {Ketyl radical reactivity via atom transfer catalysis.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {225-229}, doi = {10.1126/science.aau1777}, pmid = {30309953}, issn = {1095-9203}, support = {R35 GM119812/GM/NIGMS NIH HHS/United States ; }, abstract = {Single-electron reduction of a carbonyl to a ketyl enables access to a polarity-reversed platform of reactivity for this cornerstone functional group. However, the synthetic utility of the ketyl radical is hindered by the strong reductants necessary for its generation, which also limit its reactivity to net reductive mechanisms. We report a strategy for net redox-neutral generation and reaction of ketyl radicals. The in situ conversion of aldehydes to α-acetoxy iodides lowers their reduction potential by more than 1 volt, allowing for milder access to the corresponding ketyl radicals and an oxidative termination event. Upon subjecting these iodides to a dimanganese decacarbonyl precatalyst and visible light irradiation, an atom transfer radical addition (ATRA) mechanism affords a broad scope of vinyl iodide products with high Z-selectivity.}, } @article {pmid30309952, year = {2018}, author = {Urban, MW and Davydovich, D and Yang, Y and Demir, T and Zhang, Y and Casabianca, L}, title = {Key-and-lock commodity self-healing copolymers.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {220-225}, doi = {10.1126/science.aat2975}, pmid = {30309952}, issn = {1095-9203}, abstract = {Self-healing materials are notable for their ability to recover from physical or chemical damage. We report that commodity copolymers, such as poly(methyl methacrylate)/n-butyl acrylate [p(MMA/nBA)] and their derivatives, can self-heal upon mechanical damage. This behavior occurs in a narrow compositional range for copolymer topologies that are preferentially alternating with a random component (alternating/random) and is attributed to favorable interchain van der Waals forces forming key-and-lock interchain junctions. The use of van der Waals forces instead of supramolecular or covalent rebonding or encapsulated reactants eliminates chemical and physical alterations and enables multiple recovery upon mechanical damage without external intervention. Unlike other self-healing approaches, perturbation of ubiquitous van der Waals forces upon mechanical damage is energetically unfavorable for interdigitated alternating/random copolymer motifs that facilitate self-healing under ambient conditions.}, } @article {pmid30309951, year = {2018}, author = {Schreyer, L and Kaib, PSJ and Wakchaure, VN and Obradors, C and Properzi, R and Lee, S and List, B}, title = {Confined acids catalyze asymmetric single aldolizations of acetaldehyde enolates.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {216-219}, doi = {10.1126/science.aau0817}, pmid = {30309951}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Reactions that form a product with the same reactive functionality as that of one of the starting compounds frequently end in oligomerization. As a salient example, selective aldol coupling of the smallest, though arguably most useful, enolizable aldehyde, acetaldehyde, with just one partner substrate has proven to be extremely challenging. Here, we report a highly enantioselective Mukaiyama aldol reaction with the simple triethylsilyl (TES) and tert-butyldimethylsilyl (TBS) enolates of acetaldehyde and various aliphatic and aromatic acceptor aldehydes. The reaction is catalyzed by recently developed, strongly acidic imidodiphosphorimidates (IDPi), which, like enzymes, display a confined active site but, like small-molecule catalysts, have a broad substrate scope. The process is scalable, fast, efficient (0.5 to 1.5 mole % catalyst loading), and greatly simplifies access to highly valuable silylated acetaldehyde aldols.}, } @article {pmid30309950, year = {2018}, author = {Magnin, Y and Amara, H and Ducastelle, F and Loiseau, A and Bichara, C}, title = {Entropy-driven stability of chiral single-walled carbon nanotubes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {212-215}, doi = {10.1126/science.aat6228}, pmid = {30309950}, issn = {1095-9203}, abstract = {Single-walled carbon nanotubes are hollow cylinders that can grow centimeters long via carbon incorporation at the interface with a catalyst. They display semiconducting or metallic characteristics, depending on their helicity, which is determined during their growth. To support the quest for a selective synthesis, we develop a thermodynamic model that relates the tube-catalyst interfacial energies, temperature, and the resulting tube chirality. We show that nanotubes can grow chiral because of the configurational entropy of their nanometer-sized edge, thus explaining experimentally observed temperature evolutions of chiral distributions. Taking the chemical nature of the catalyst into account through interfacial energies, we derive structural maps and phase diagrams that will guide a rational choice of a catalyst and growth parameters toward a better selectivity.}, } @article {pmid30309949, year = {2018}, author = {Chen, J and Quiles-Puchalt, N and Chiang, YN and Bacigalupe, R and Fillol-Salom, A and Chee, MSJ and Fitzgerald, JR and Penadés, JR}, title = {Genome hypermobility by lateral transduction.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {207-212}, doi = {10.1126/science.aat5867}, pmid = {30309949}, issn = {1095-9203}, support = {BB/I013873/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/M003876/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Chromosomes, Bacterial/genetics/virology ; DNA Packaging ; Genome, Bacterial ; Lysogeny/genetics/physiology ; Prophages/genetics/physiology ; Staphylococcus Phages/genetics/*physiology ; Staphylococcus aureus/genetics/*virology ; *Transduction, Genetic ; Virus Activation/genetics/physiology ; Virus Replication ; }, abstract = {Genetic transduction is a major evolutionary force that underlies bacterial adaptation. Here we report that the temperate bacteriophages of Staphylococcus aureus engage in a distinct form of transduction we term lateral transduction. Staphylococcal prophages do not follow the previously described excision-replication-packaging pathway but instead excise late in their lytic program. Here, DNA packaging initiates in situ from integrated prophages, and large metameric spans including several hundred kilobases of the S. aureus genome are packaged in phage heads at very high frequency. In situ replication before DNA packaging creates multiple prophage genomes so that lateral-transducing particles form during normal phage maturation, transforming parts of the S. aureus chromosome into hypermobile regions of gene transfer.}, } @article {pmid30309948, year = {2018}, author = {De, K and Kasliwal, MM and Ofek, EO and Moriya, TJ and Burke, J and Cao, Y and Cenko, SB and Doran, GB and Duggan, GE and Fender, RP and Fransson, C and Gal-Yam, A and Horesh, A and Kulkarni, SR and Laher, RR and Lunnan, R and Manulis, I and Masci, F and Mazzali, PA and Nugent, PE and Perley, DA and Petrushevska, T and Piro, AL and Rumsey, C and Sollerman, J and Sullivan, M and Taddia, F}, title = {A hot and fast ultra-stripped supernova that likely formed a compact neutron star binary.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {201-206}, doi = {10.1126/science.aas8693}, pmid = {30309948}, issn = {1095-9203}, abstract = {Compact neutron star binary systems are produced from binary massive stars through stellar evolution involving up to two supernova explosions. The final stages in the formation of these systems have not been directly observed. We report the discovery of iPTF 14gqr (SN 2014ft), a type Ic supernova with a fast-evolving light curve indicating an extremely low ejecta mass (≈0.2 solar masses) and low kinetic energy (≈2 × 1050 ergs). Early photometry and spectroscopy reveal evidence of shock cooling of an extended helium-rich envelope, likely ejected in an intense pre-explosion mass-loss episode of the progenitor. Taken together, we interpret iPTF 14gqr as evidence for ultra-stripped supernovae that form neutron stars in compact binary systems.}, } @article {pmid30309947, year = {2018}, author = {Briscoe, SD and Ragsdale, CW}, title = {Homology, neocortex, and the evolution of developmental mechanisms.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {190-193}, doi = {10.1126/science.aau3711}, pmid = {30309947}, issn = {1095-9203}, support = {T32 GM007183/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Birds ; Cognition/physiology ; Gene Regulatory Networks ; Mice ; Neocortex/*cytology/*embryology/physiology ; Neural Pathways ; Neurons/*physiology ; }, abstract = {The six-layered neocortex of the mammalian pallium has no clear homolog in birds or non-avian reptiles. Recent research indicates that although these extant amniotes possess a variety of divergent and nonhomologous pallial structures, they share a conserved set of neuronal cell types and circuitries. These findings suggest a principle of brain evolution: that natural selection preferentially preserves the integrity of information-processing pathways, whereas other levels of biological organization, such as the three-dimensional architectures of neuronal assemblies, are less constrained. We review the similarities of pallial neuronal cell types in amniotes, delineate candidate gene regulatory networks for their cellular identities, and propose a model of developmental evolution for the divergence of amniote pallial structures.}, } @article {pmid30309946, year = {2018}, author = {Thion, MS and Ginhoux, F and Garel, S}, title = {Microglia and early brain development: An intimate journey.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {185-189}, doi = {10.1126/science.aat0474}, pmid = {30309946}, issn = {1095-9203}, mesh = {Animals ; Apoptosis ; Brain/*embryology/*immunology ; Cell Communication ; Mice ; Microbiota/physiology ; Microglia/*immunology ; Neurons/*immunology ; }, abstract = {Cross-talk between the nervous and immune systems has been well described in the context of adult physiology and disease. Recent advances in our understanding of immune cell ontogeny have revealed a notable interplay between neurons and microglia during the prenatal and postnatal emergence of functional circuits. This Review focuses on the brain, where the early symbiotic relationship between microglia and neuronal cells critically regulates wiring, contributes to sex-specific differences in neural circuits, and relays crucial information from the periphery, including signals derived from the microbiota. These observations underscore the importance of studying neurodevelopment as part of a broader framework that considers nervous system interactions with microglia in a whole-body context.}, } @article {pmid30309945, year = {2018}, author = {Allen, NJ and Lyons, DA}, title = {Glia as architects of central nervous system formation and function.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {181-185}, pmid = {30309945}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; R01 NS089791/NS/NINDS NIH HHS/United States ; R01 NS105742/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Movement ; Central Nervous System/blood supply/*cytology/*embryology ; Mice ; Neurogenesis ; Neuroglia/cytology/*physiology ; Neuronal Plasticity ; Neurons/cytology/physiology ; Synapses ; Synaptic Transmission ; }, abstract = {Glia constitute roughly half of the cells of the central nervous system (CNS) but were long-considered to be static bystanders to its formation and function. Here we provide an overview of how the diverse and dynamic functions of glial cells orchestrate essentially all aspects of nervous system formation and function. Radial glia, astrocytes, oligodendrocyte progenitor cells, oligodendrocytes, and microglia each influence nervous system development, from neuronal birth, migration, axon specification, and growth through circuit assembly and synaptogenesis. As neural circuits mature, distinct glia fulfill key roles in synaptic communication, plasticity, homeostasis, and network-level activity through dynamic monitoring and alteration of CNS structure and function. Continued elucidation of glial cell biology, and the dynamic interactions of neurons and glia, will enrich our understanding of nervous system formation, health, and function.}, } @article {pmid30309944, year = {2018}, author = {Holguera, I and Desplan, C}, title = {Neuronal specification in space and time.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {176-180}, doi = {10.1126/science.aas9435}, pmid = {30309944}, issn = {1095-9203}, support = {R01 EY013012/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Cell Count ; Cell Division ; Mice ; *Neural Pathways ; Neural Stem Cells/*physiology ; Neurons/*physiology ; Organ Specificity ; Single-Cell Analysis ; Somatosensory Cortex/cytology/*growth & development/physiology ; }, abstract = {To understand how neurons assemble to form functional circuits, it is necessary to obtain a detailed knowledge of their diversity and to define the developmental specification programs that give rise to this diversity. Invertebrates and vertebrates appear to share common developmental principles of neuronal specification in which cascades of transcription factors temporally pattern progenitors, while spatial cues modify the outcomes of this temporal patterning. Here, we highlight these conserved mechanisms and describe how they are used in distinct neural structures. We present the questions that remain for a better understanding of neuronal specification. Single-cell RNA profiling approaches will potentially shed light on these questions, allowing not only the characterization of neuronal diversity in adult brains, but also the investigation of the developmental trajectories leading to the generation and maintenance of this diversity.}, } @article {pmid30309943, year = {2018}, author = {Furfaro, H and , }, title = {A fragile existence.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {172-175}, doi = {10.1126/science.362.6411.172}, pmid = {30309943}, issn = {1095-9203}, mesh = {Cities ; Colombia ; Female ; Fragile X Syndrome/*genetics ; Humans ; Male ; Membrane Glycoproteins/*genetics ; Mosaicism ; Mucins/*genetics ; Mutation ; Pedigree ; Receptors, G-Protein-Coupled/*genetics ; }, } @article {pmid30309942, year = {2018}, author = {Hines, PJ}, title = {Mind-boggling brain development.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {170-171}, doi = {10.1126/science.aav5687}, pmid = {30309942}, issn = {1095-9203}, mesh = {Brain/cytology/*growth & development/physiology ; Humans ; *Neurogenesis ; Neuroglia/physiology ; Neurons/physiology ; }, } @article {pmid30309941, year = {2018}, author = {Lerner, TN}, title = {The effortless custody of automatism.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {169}, doi = {10.1126/science.aav1250}, pmid = {30309941}, issn = {1095-9203}, mesh = {Animals ; *Automatism ; Corpus Striatum/cytology/*metabolism ; Dopamine/*metabolism ; Dopaminergic Neurons/*metabolism ; *Habits ; *Signal Transduction ; }, } @article {pmid30309940, year = {2018}, author = {Nowakowski, TJ}, title = {Building blocks of the human brain.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {169}, doi = {10.1126/science.aav1252}, pmid = {30309940}, issn = {1095-9203}, mesh = {Cerebral Cortex/*cytology/*physiology ; *Cortical Excitability ; Humans ; Neuroglia/cytology/*physiology ; Neurons/cytology/*physiology ; }, } @article {pmid30309939, year = {2018}, author = {Kohl, J}, title = {Circuits for care.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {168-169}, doi = {10.1126/science.aav1249}, pmid = {30309939}, issn = {1095-9203}, mesh = {Animals ; Galanin/metabolism ; Models, Neurological ; Neural Pathways/*physiology ; Neurons/metabolism/*physiology ; *Parenting ; Preoptic Area/cytology/*physiology ; }, } @article {pmid30309938, year = {2018}, author = {Miner, K and Wayant, N and Ward, H}, title = {Preventing chemical release in hurricanes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {166}, doi = {10.1126/science.aav3822}, pmid = {30309938}, issn = {1095-9203}, mesh = {*Cyclonic Storms ; Disaster Planning ; *Disasters ; }, } @article {pmid30309937, year = {2018}, author = {Aguilar, XF and Fine, AE and Pruvot, M and Njeumi, F and Walzer, C and Kock, R and Shiilegdamba, E}, title = {PPR virus threatens wildlife conservation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {165-166}, doi = {10.1126/science.aav4096}, pmid = {30309937}, issn = {1095-9203}, mesh = {Animals ; *Conservation of Natural Resources ; Peste-des-Petits-Ruminants/*epidemiology/*virology ; *Peste-des-petits-ruminants virus ; *Ruminants ; }, } @article {pmid30309936, year = {2018}, author = {Berg, J}, title = {Editor's note: Harassment policy.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {165}, doi = {10.1126/science.aav6183}, pmid = {30309936}, issn = {1095-9203}, mesh = {Editorial Policies ; *Harassment, Non-Sexual ; *Periodicals as Topic ; *Sexual Harassment ; }, } @article {pmid30309935, year = {2018}, author = {Wolf, SM and Evans, BJ}, title = {Return of results and data to study participants.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {159-160}, doi = {10.1126/science.aav0005}, pmid = {30309935}, issn = {1095-9203}, support = {R01 HG008605/HG/NHGRI NIH HHS/United States ; }, mesh = {Access to Information/*ethics ; *Bioethical Issues ; Biomedical Research/*ethics ; Confidentiality/*ethics ; Humans ; }, } @article {pmid30309934, year = {2018}, author = {Blackburn, JM and Roizen, JL}, title = {Easy access to elusive radical reactions.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {157-158}, doi = {10.1126/science.aav0574}, pmid = {30309934}, issn = {1095-9203}, } @article {pmid30309933, year = {2018}, author = {Koonin, EV and Makarova, KS}, title = {Anti-CRISPRs on the march.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {156-157}, doi = {10.1126/science.aav2440}, pmid = {30309933}, issn = {1095-9203}, mesh = {*Clustered Regularly Interspaced Short Palindromic Repeats ; *Genome, Bacterial ; Sequence Analysis, DNA ; }, } @article {pmid30309932, year = {2018}, author = {Bluestone, JA and Tang, Q}, title = {Treg cells-the next frontier of cell therapy.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {154-155}, doi = {10.1126/science.aau2688}, pmid = {30309932}, issn = {1095-9203}, mesh = {Adoptive Transfer/*methods ; Autoimmune Diseases/*therapy ; Cell- and Tissue-Based Therapy/*methods ; Clinical Trials as Topic ; Humans ; T-Lymphocytes, Regulatory/*immunology/transplantation ; }, } @article {pmid30309931, year = {2018}, author = {Davidson, AR}, title = {A common trick for transferring bacterial DNA.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {152-153}, doi = {10.1126/science.aav1723}, pmid = {30309931}, issn = {1095-9203}, support = {//CIHR/Canada ; }, mesh = {*DNA, Bacterial ; }, } @article {pmid30309930, year = {2018}, author = {Herhaus, L and Dikic, I}, title = {Dimerization quality control via ubiquitylation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {151-152}, doi = {10.1126/science.aav1391}, pmid = {30309930}, issn = {1095-9203}, mesh = {*Dimerization ; Quality Control ; Ubiquitin ; *Ubiquitination ; }, } @article {pmid30309929, year = {2018}, author = {Sumerlin, BS}, title = {Next-generation self-healing materials.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {150-151}, doi = {10.1126/science.aau6453}, pmid = {30309929}, issn = {1095-9203}, } @article {pmid30309928, year = {2018}, author = {Ignatieva, M and Hedblom, M}, title = {An alternative urban green carpet.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {148-149}, doi = {10.1126/science.aau6974}, pmid = {30309928}, issn = {1095-9203}, mesh = {*Climate Change ; Environmental Monitoring ; Gardens ; *Grassland ; Parks, Recreational ; *Urban Renewal ; }, } @article {pmid30309927, year = {2018}, author = {Stokstad, E}, title = {Vive la resistant vines!.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {146}, doi = {10.1126/science.362.6411.146}, pmid = {30309927}, issn = {1095-9203}, mesh = {*Disease Resistance/genetics ; France ; Pesticides/*toxicity ; Plant Diseases/*microbiology ; Vitis/*microbiology ; *Wine ; }, } @article {pmid30309926, year = {2018}, author = {Stokstad, E}, title = {A new leaf.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {144-147}, doi = {10.1126/science.362.6411.144}, pmid = {30309926}, issn = {1095-9203}, mesh = {Copper Sulfate/toxicity ; *Crops, Agricultural/economics/microbiology/parasitology ; Food Safety ; France ; Herbicides/economics/*toxicity ; Insecticides/economics/*toxicity ; Plant Diseases/microbiology/parasitology/*prevention & control ; Plant Leaves/microbiology/parasitology ; }, } @article {pmid30309925, year = {2018}, author = {Service, RF}, title = {DNA printers poised to jump from paragraphs to pages.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {143}, doi = {10.1126/science.362.6411.143}, pmid = {30309925}, issn = {1095-9203}, mesh = {DNA/*biosynthesis/chemistry ; DNA Nucleotidylexotransferase/*chemistry ; Synthetic Biology/*methods ; }, } @article {pmid30309924, year = {2018}, author = {Service, RF}, title = {Protein evolution earns chemistry Nobel.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {142}, doi = {10.1126/science.362.6411.142}, pmid = {30309924}, issn = {1095-9203}, mesh = {*Chemistry ; *Directed Molecular Evolution ; *Nobel Prize ; Proteins/*chemistry ; }, } @article {pmid30309923, year = {2018}, author = {Leslie, M}, title = {Replumbing the lymphatic system.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {140-141}, doi = {10.1126/science.362.6411.140}, pmid = {30309923}, issn = {1095-9203}, mesh = {Clinical Trials, Phase I as Topic ; Female ; Genetic Therapy/methods ; Humans ; *Lymph ; Lymphatic Vessels/physiology/*physiopathology ; Lymphedema/etiology/physiopathology/*therapy ; Regeneration ; Vascular Endothelial Growth Factor C/genetics ; }, } @article {pmid30309922, year = {2018}, author = {Voosen, P}, title = {NASA's next Mars rover aims to explore two promising sites.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {139-140}, doi = {10.1126/science.362.6411.139}, pmid = {30309922}, issn = {1095-9203}, } @article {pmid30309921, year = {2018}, author = {Cartlidge, E}, title = {Leaks put Italy's underground lab in jeopardy.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {138-139}, doi = {10.1126/science.362.6411.138}, pmid = {30309921}, issn = {1095-9203}, mesh = {*Chemical Safety ; *Drinking Water ; Italy ; Laboratories ; *Water Pollution ; *Water Supply ; }, } @article {pmid30309920, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {134-136}, doi = {10.1126/science.362.6411.134}, pmid = {30309920}, issn = {1095-9203}, } @article {pmid30309919, year = {2018}, author = {Murakami, Y and Borgonovi, F}, title = {Japan needs gender equality.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {133}, doi = {10.1126/science.aav6236}, pmid = {30309919}, issn = {1095-9203}, mesh = {Japan ; Medicine/*trends ; *Physicians ; *Sexism ; *Women's Rights ; *Workforce ; }, } @article {pmid30309918, year = {2018}, author = {Willhoft, O and Ghoneim, M and Lin, CL and Chua, EYD and Wilkinson, M and Chaban, Y and Ayala, R and McCormack, EA and Ocloo, L and Rueda, DS and Wigley, DB}, title = {Structure and dynamics of the yeast SWR1-nucleosome complex.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {}, doi = {10.1126/science.aat7716}, pmid = {30309918}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; //Cancer Research UK/United Kingdom ; //Medical Research Council/United Kingdom ; }, mesh = {Adenosine Triphosphatases/*chemistry/ultrastructure ; Adenosine Triphosphate/metabolism ; Chromatin Assembly and Disassembly ; Cryoelectron Microscopy ; Nucleosomes/*chemistry/ultrastructure ; Protein Domains ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/ultrastructure ; }, abstract = {The yeast SWR1 complex exchanges histone H2A in nucleosomes with Htz1 (H2A.Z in humans). The cryo-electron microscopy structure of the SWR1 complex bound to a nucleosome at 3.6-angstrom resolution reveals details of the intricate interactions between components of the SWR1 complex and its nucleosome substrate. Interactions between the Swr1 motor domains and the DNA wrap at superhelical location 2 distort the DNA, causing a bulge with concomitant translocation of the DNA by one base pair, coupled to conformational changes of the histone core. Furthermore, partial unwrapping of the DNA from the histone core takes place upon binding of nucleosomes to SWR1 complex. The unwrapping, as monitored by single-molecule data, is stabilized and has its dynamics altered by adenosine triphosphate binding but does not require hydrolysis.}, } @article {pmid30309917, year = {2018}, author = {}, title = {Erratum for the Research Article "Saturn's magnetic field revealed by the Cassini Grand Finale" by M. K. Dougherty, H. Cao, K. K. Khurana, G. J. Hunt, G. Provan, S. Kellock, M. E. Burton, T. A. Burk, E. J. Bunce, S. W. H. Cowley, M. G. Kivelson, C. T. Russell, D. J. Southwood.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {}, doi = {10.1126/science.aav6732}, pmid = {30309917}, issn = {1095-9203}, } @article {pmid30309916, year = {2018}, author = {Eldred, KC and Hadyniak, SE and Hussey, KA and Brenerman, B and Zhang, PW and Chamling, X and Sluch, VM and Welsbie, DS and Hattar, S and Taylor, J and Wahlin, K and Zack, DJ and Johnston, RJ}, title = {Thyroid hormone signaling specifies cone subtypes in human retinal organoids.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {}, pmid = {30309916}, issn = {1095-9203}, support = {R01 EY025598/EY/NEI NIH HHS/United States ; T32 GM007231/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {CRISPR-Cas Systems ; Cell Line ; Embryonic Stem Cells/metabolism ; *Gene Expression Regulation, Developmental ; Humans ; Mutation ; Organoids/*growth & development/metabolism ; Proteolysis ; Retina/cytology/*growth & development ; Retinal Cone Photoreceptor Cells/*classification ; Thyroid Hormones/*metabolism ; }, abstract = {The mechanisms underlying specification of neuronal subtypes within the human nervous system are largely unknown. The blue (S), green (M), and red (L) cones of the retina enable high-acuity daytime and color vision. To determine the mechanism that controls S versus L/M fates, we studied the differentiation of human retinal organoids. Organoids and retinas have similar distributions, expression profiles, and morphologies of cone subtypes. S cones are specified first, followed by L/M cones, and thyroid hormone signaling controls this temporal switch. Dynamic expression of thyroid hormone-degrading and -activating proteins within the retina ensures low signaling early to specify S cones and high signaling late to produce L/M cones. This work establishes organoids as a model for determining mechanisms of human development with promising utility for therapeutics and vision repair.}, } @article {pmid30309915, year = {2018}, author = {Cristescu, R and Mogg, R and Ayers, M and Albright, A and Murphy, E and Yearley, J and Sher, X and Liu, XQ and Lu, H and Nebozhyn, M and Zhang, C and Lunceford, JK and Joe, A and Cheng, J and Webber, AL and Ibrahim, N and Plimack, ER and Ott, PA and Seiwert, TY and Ribas, A and McClanahan, TK and Tomassini, JE and Loboda, A and Kaufman, D}, title = {Pan-tumor genomic biomarkers for PD-1 checkpoint blockade-based immunotherapy.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {}, doi = {10.1126/science.aar3593}, pmid = {30309915}, issn = {1095-9203}, mesh = {Antibodies, Monoclonal, Humanized/*therapeutic use ; Antineoplastic Agents, Immunological/*therapeutic use ; Biomarkers, Tumor/*genetics ; Cell Cycle Checkpoints ; Genetic Markers ; Humans ; Immunotherapy ; Inflammation/genetics ; Molecular Targeted Therapy/*methods ; Mutation ; Neoplasms/*genetics/*therapy ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; T-Lymphocytes/immunology ; Transcriptome ; Tumor Burden/genetics ; }, abstract = {Programmed cell death protein-1 (PD-1) and programmed cell death ligand-1 (PD-L1) checkpoint blockade immunotherapy elicits durable antitumor effects in multiple cancers, yet not all patients respond. We report the evaluation of >300 patient samples across 22 tumor types from four KEYNOTE clinical trials. Tumor mutational burden (TMB) and a T cell-inflamed gene expression profile (GEP) exhibited joint predictive utility in identifying responders and nonresponders to the PD-1 antibody pembrolizumab. TMB and GEP were independently predictive of response and demonstrated low correlation, suggesting that they capture distinct features of neoantigenicity and T cell activation. Analysis of The Cancer Genome Atlas database showed TMB and GEP to have a low correlation, and analysis by joint stratification revealed biomarker-defined patterns of targetable-resistance biology. These biomarkers may have utility in clinical trial design by guiding rational selection of anti-PD-1 monotherapy and combination immunotherapy regimens.}, } @article {pmid30309914, year = {2018}, author = {Hoffmann, DL and Standish, CD and García-Diez, M and Pettitt, PB and Milton, JA and Zilhão, J and Alcolea-González, JJ and Cantalejo-Duarte, P and Collado, H and de Balbín, R and Lorblanchet, M and Ramos-Muñoz, J and Weniger, GC and Pike, AWG}, title = {Response to Comment on "U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art".}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {}, doi = {10.1126/science.aau1736}, pmid = {30309914}, issn = {1095-9203}, mesh = {Carbonates ; *Caves ; *Neanderthals ; Reproducibility of Results ; Spain ; }, abstract = {Slimak et al challenge the reliability of our oldest (>65,000 years) U-Th dates on carbonates associated with cave paintings in Spain. They cite a supposed lack of parietal art for the 25,000 years following this date, along with potential methodological issues relating to open-system behavior and corrections to detrital or source water 230Th. We show that their criticisms are unfounded.}, } @article {pmid30309909, year = {2018}, author = {Meier, EJ and An, FA and Dauphin, A and Maffei, M and Massignan, P and Hughes, TL and Gadway, B}, title = {Observation of the topological Anderson insulator in disordered atomic wires.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6417}, pages = {929-933}, doi = {10.1126/science.aat3406}, pmid = {30309909}, issn = {1095-9203}, abstract = {Topology and disorder have a rich combined influence on quantum transport. To probe their interplay, we synthesized one-dimensional chiral symmetric wires with controllable disorder via spectroscopic Hamiltonian engineering, based on the laser-driven coupling of discrete momentum states of ultracold atoms. Measuring the bulk evolution of a topological indicator after a sudden quench, we observed the topological Anderson insulator phase, in which added disorder drives the band structure of a wire from topologically trivial to nontrivial. In addition, we observed the robustness of topologically nontrivial wires to weak disorder and measured the transition to a trivial phase in the presence of strong disorder. Atomic interactions in this quantum simulation platform may enable realizations of strongly interacting topological fluids.}, } @article {pmid30309908, year = {2018}, author = {de la Peña, AH and Goodall, EA and Gates, SN and Lander, GC and Martin, A}, title = {Substrate-engaged 26S proteasome structures reveal mechanisms for ATP-hydrolysis-driven translocation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6418}, pages = {}, doi = {10.1126/science.aav0725}, pmid = {30309908}, issn = {1095-9203}, support = {DP2 EB020402/EB/NIBIB NIH HHS/United States ; R01 GM094497/GM/NIGMS NIH HHS/United States ; S10 OD021634/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {The 26S proteasome is the primary eukaryotic degradation machine and thus is critically involved in numerous cellular processes. The heterohexameric adenosine triphosphatase (ATPase) motor of the proteasome unfolds and translocates targeted protein substrates into the open gate of a proteolytic core while a proteasomal deubiquitinase concomitantly removes substrate-attached ubiquitin chains. However, the mechanisms by which ATP hydrolysis drives the conformational changes responsible for these processes have remained elusive. Here we present the cryo-electron microscopy structures of four distinct conformational states of the actively ATP-hydrolyzing, substrate-engaged 26S proteasome. These structures reveal how mechanical substrate translocation accelerates deubiquitination and how ATP-binding, -hydrolysis, and phosphate-release events are coordinated within the AAA+ (ATPases associated with diverse cellular activities) motor to induce conformational changes and propel the substrate through the central pore.}, } @article {pmid30309907, year = {2018}, author = {Erlich, Y and Shor, T and Pe'er, I and Carmi, S}, title = {Identity inference of genomic data using long-range familial searches.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {690-694}, doi = {10.1126/science.aau4832}, pmid = {30309907}, issn = {1095-9203}, abstract = {Consumer genomics databases have reached the scale of millions of individuals. Recently, law enforcement authorities have exploited some of these databases to identify suspects via distant familial relatives. Using genomic data of 1.28 million individuals tested with consumer genomics, we investigated the power of this technique. We project that about 60% of the searches for individuals of European descent will result in a third-cousin or closer match, which theoretically allows their identification using demographic identifiers. Moreover, the technique could implicate nearly any U.S. individual of European descent in the near future. We demonstrate that the technique can also identify research participants of a public sequencing project. On the basis of these results, we propose a potential mitigation strategy and policy implications for human subject research.}, } @article {pmid30309906, year = {2018}, author = {Shim, J and Bae, SH and Kong, W and Lee, D and Qiao, K and Nezich, D and Park, YJ and Zhao, R and Sundaram, S and Li, X and Yeon, H and Choi, C and Kum, H and Yue, R and Zhou, G and Ou, Y and Lee, K and Moodera, J and Zhao, X and Ahn, JH and Hinkle, C and Ougazzaden, A and Kim, J}, title = {Controlled crack propagation for atomic precision handling of wafer-scale two-dimensional materials.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {665-670}, doi = {10.1126/science.aat8126}, pmid = {30309906}, issn = {1095-9203}, abstract = {Although flakes of two-dimensional (2D) heterostructures at the micrometer scale can be formed with adhesive-tape exfoliation methods, isolation of 2D flakes into monolayers is extremely time consuming because it is a trial-and-error process. Controlling the number of 2D layers through direct growth also presents difficulty because of the high nucleation barrier on 2D materials. We demonstrate a layer-resolved 2D material splitting technique that permits high-throughput production of multiple monolayers of wafer-scale (5-centimeter diameter) 2D materials by splitting single stacks of thick 2D materials grown on a single wafer. Wafer-scale uniformity of hexagonal boron nitride, tungsten disulfide, tungsten diselenide, molybdenum disulfide, and molybdenum diselenide monolayers was verified by photoluminescence response and by substantial retention of electronic conductivity. We fabricated wafer-scale van der Waals heterostructures, including field-effect transistors, with single-atom thickness resolution.}, } @article {pmid30309905, year = {2018}, author = {Real, R and Peter, M and Trabalza, A and Khan, S and Smith, MA and Dopp, J and Barnes, SJ and Momoh, A and Strano, A and Volpi, E and Knott, G and Livesey, FJ and De Paola, V}, title = {In vivo modeling of human neuron dynamics and Down syndrome.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {}, doi = {10.1126/science.aau1810}, pmid = {30309905}, issn = {1095-9203}, abstract = {Harnessing the potential of human stem cells for modeling the physiology and diseases of cortical circuitry requires monitoring cellular dynamics in vivo. We show that human induced pluripotent stem cell (iPSC)-derived cortical neurons transplanted into the adult mouse cortex consistently organized into large (up to ~100 mm3) vascularized neuron-glia territories with complex cytoarchitecture. Longitudinal imaging of >4000 grafted developing human neurons revealed that neuronal arbors refined via branch-specific retraction; human synaptic networks substantially restructured over 4 months, with balanced rates of synapse formation and elimination; and oscillatory population activity mirrored the patterns of fetal neural networks. Lastly, we found increased synaptic stability and reduced oscillations in transplants from two individuals with Down syndrome, demonstrating the potential of in vivo imaging in human tissue grafts for patient-specific modeling of cortical development, physiology, and pathogenesis.}, } @article {pmid30309904, year = {2018}, author = {Turren-Cruz, SH and Hagfeldt, A and Saliba, M}, title = {Methylammonium-free, high-performance, and stable perovskite solar cells on a planar architecture.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {449-453}, doi = {10.1126/science.aat3583}, pmid = {30309904}, issn = {1095-9203}, abstract = {Currently, perovskite solar cells (PSCs) with high performances greater than 20% contain bromine (Br), causing a suboptimal bandgap, and the thermally unstable methylammonium (MA) molecule. Avoiding Br and especially MA can therefore result in more optimal bandgaps and stable perovskites. We show that inorganic cation tuning, using rubidium and cesium, enables highly crystalline formamidinium-based perovskites without Br or MA. On a conventional, planar device architecture, using polymeric interlayers at the electron- and hole-transporting interface, we demonstrate an efficiency of 20.35% (stabilized), one of the highest for MA-free perovskites, with a drastically improved stability reached without the stabilizing influence of mesoporous interlayers. The perovskite is not heated beyond 100°C. Going MA-free is a new direction for perovskites that are inherently stable and compatible with tandems or flexible substrates, which are the main routes commercializing PSCs.}, } @article {pmid30309754, year = {2018}, author = {Yeung, J and Naef, F}, title = {Rhythms of the Genome: Circadian Dynamics from Chromatin Topology, Tissue-Specific Gene Expression, to Behavior.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {12}, pages = {915-926}, doi = {10.1016/j.tig.2018.09.005}, pmid = {30309754}, issn = {0168-9525}, abstract = {Circadian rhythms in physiology and behavior evolved to resonate with daily cycles in the external environment. In mammals, organs orchestrate temporal physiology over the 24-h day, which requires extensive gene expression rhythms targeted to the right tissue. Although a core set of gene products oscillates across virtually all cell types, gene expression profiling across tissues over the 24-h day showed that rhythmic gene expression programs are tissue specific. We highlight recent progress in uncovering how the circadian clock interweaves with tissue-specific gene regulatory networks involving functions such as xenobiotic metabolism, glucose homeostasis, and sleep. This progress hinges on not only comprehensive experimental approaches but also computational methods for multivariate analysis of periodic functional genomics data. We emphasize dynamic chromatin interactions as a novel regulatory layer underlying circadian gene transcription, core clock functions, and ultimately behavior. Finally, we discuss perspectives on extending the knowledge of the circadian clock in animals to human chronobiology.}, } @article {pmid30309615, year = {2018}, author = {Borensztejn, A and Mascaro, A and Wharton, KA}, title = {Corrigendum to "JAK/STAT signaling prevents excessive apoptosis to ensure maintenance of the interfollicular stalk critical for Drosophila oogenesis" [Dev. Biol. 438 (2018) 1-9].}, journal = {Developmental biology}, volume = {444}, number = {1}, pages = {41}, doi = {10.1016/j.ydbio.2018.09.020}, pmid = {30309615}, issn = {1095-564X}, support = {R01 GM068118/GM/NIGMS NIH HHS/United States ; }, } @article {pmid30309394, year = {2018}, author = {Tozaki, T and Gamo, S and Takasu, M and Kikuchi, M and Kakoi, H and Hirota, KI and Kusano, K and Nagata, SI}, title = {Digital PCR detection of plasmid DNA administered to the skeletal muscle of a microminipig: a model case study for gene doping detection.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {708}, pmid = {30309394}, issn = {1756-0500}, support = {2017-2019//JAPAN RACING ASSOCIATION/ ; }, mesh = {Animals ; DNA Fragmentation ; Doping in Sports/methods/*prevention & control ; Erythropoietin/blood/*genetics/pharmacokinetics ; Gene Expression ; Horses ; Humans ; Injections, Intramuscular ; Male ; Plasmids/administration & dosage/*chemistry/metabolism ; Polymerase Chain Reaction/*methods ; Recombinant Proteins/blood/genetics/pharmacokinetics ; Sensitivity and Specificity ; Swine ; Swine, Miniature ; Transgenes ; }, abstract = {OBJECTIVE: Doping control is an important and indispensable aspect of fair horse racing; genetic doping has been recently included to this. In this study, we aimed to develop a detection method of gene doping. A plasmid cloned with human erythropoietin gene (p.hEPO, 250 μg/head) was intramuscularly injected into a microminipig. Subsequently, p.hEPO was extracted from 1 mL of plasma and detected by droplet digital polymerase chain reaction.

RESULTS: The results confirmed that the maximum amount of plasmid was detected at 15 min after administration and the majority of the plasmid was degraded in the bloodstream within 1-2 days after administration. In contrast, low amounts of p.hEPO were detected at 2-3 weeks after administration. These results suggest that the proposed method to detect gene doping can help obtain information for experiments using horses.}, } @article {pmid30309393, year = {2018}, author = {Kopczynska, M and Sharif, B and Cleaver, S and Spencer, N and Kurani, A and Lee, C and Davis, J and Durie, C and Joseph-Gubral, J and Sharma, A and Allen, L and Atkins, B and Gordon, A and Jones, L and Noble, A and Bradley, M and Atkinson, H and Inns, J and Penney, H and Gilbert, C and Walford, R and Pike, L and Edwards, R and Howcroft, R and Preston, H and Gee, J and Doyle, N and Maden, C and Smith, C and Nik Azis, NS and Vadivale, N and Szakmany, T and , }, title = {Sepsis-related deaths in the at-risk population on the wards: attributable fraction of mortality in a large point-prevalence study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {720}, pmid = {30309393}, issn = {1756-0500}, support = {2016//Fiona Elizabeth Agnew Trust Features Award/ ; 2015//Welsh Intensive Care Society/ ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cause of Death/*trends ; Cross-Sectional Studies ; Emergency Service, Hospital/*statistics & numerical data ; Female ; Hospital Mortality/*trends ; Hospitals/statistics & numerical data ; Humans ; Male ; Middle Aged ; Organ Dysfunction Scores ; Patients' Rooms/*statistics & numerical data ; Prevalence ; Risk Factors ; Sepsis/epidemiology/*mortality/pathology ; United Kingdom/epidemiology ; }, abstract = {OBJECTIVE: Sepsis mortality is reported to be high worldwide, however recently the attributable fraction of mortality due to sepsis (AFsepsis) has been questioned. If improvements in treatment options are to be evaluated, it is important to know what proportion of deaths are potentially preventable or modifiable after a sepsis episode. The aim of the study was to establish the fraction of deaths directly related to the sepsis episode on the general wards and emergency departments.

RESULTS: 839 patients were recruited over the two 24-h periods in 2016 and 2017. 521 patients fulfilled SEPSIS-3 criteria. 166 patients (32.4%) with sepsis and 56 patients (17.6%) without sepsis died within 90 days. Out of the 166 sepsis deaths 12 (7.2%) could have been directly related to sepsis, 28 (16.9%) possibly related and 96 (57.8%) were not related to sepsis. Overall AFsepsis was 24.1%. Upon analysis of the 40 deaths likely to be attributable to sepsis, we found that 31 patients (77.5%) had the Clinical Frailty Score ≥ 6, 28 (70%) had existing DNA-CPR order and 17 had limitations of care orders (42.5%).}, } @article {pmid30309386, year = {2018}, author = {Signorile, PG and Severino, A and Santoro, M and Spyrou, M and Viceconte, R and Baldi, A}, title = {Methylation analysis of HOXA10 regulatory elements in patients with endometriosis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {722}, pmid = {30309386}, issn = {1756-0500}, mesh = {Adult ; Cohort Studies ; CpG Islands ; *DNA Methylation ; Endometriosis/*genetics/metabolism/pathology ; Endometrium/metabolism/pathology ; *Epigenesis, Genetic ; Female ; Homeodomain Proteins/*genetics/metabolism ; Humans ; *Promoter Regions, Genetic ; }, abstract = {OBJECTIVE: The pathogenesis of endometriosis is still mysterious, being retrograde menstruation and coelomic metaplasia the most accepted hypotheses. Recently, it has been proposed that endometriosis is caused by fine-tuning alterations of the female genital system development during the foetal life and that in utero exposition to endocrine disruptors can be one of the factors causing the disease, possibly acting on the methylation status of the genome. In this study, we have evaluated the methylation status of HOXA10 gene regulation regions in a cohort of 22 endometriosis patients respect to a control group of 6 healthy women.

RESULTS: The methylation study was carried out on three CpG islands, previously described hypermethylated in the endometrium of endometriosis patients and include 22 CpG sites, 21 CpG sites and 10 CpG sites, respectively identified through the online platform MethPrimer. The analysis did not find significant differences between patients with endometriosis and healthy control individuals. These results confirm previous studies on genome wide methylation analysis in endometriosis patients. Therefore, other epigenetically altered genes should be considered more related to the pathogenesis of endometriosis.}, } @article {pmid30309385, year = {2018}, author = {Mbange, AE and Kaba, D and Diouara, AAM and Diop-Ndiaye, H and Ngom-Ngueye, NF and Dieng, A and Lo, S and Toure, KN and Fall, M and Mbacham, WF and Diallo, MS and Cisse, M and Mboup, S and Kane, CT}, title = {Surveillance of transmitted HIV-1 antiretroviral drug resistance in the context of decentralized HIV care in Senegal and the Ebola outbreak in Guinea.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {723}, pmid = {30309385}, issn = {1756-0500}, support = {1049-WANETAM EDCTP-RegNet-2015//European and Developing Countries Clinical Trials Partnership/ ; }, mesh = {Adult ; Anti-HIV Agents/*supply & distribution ; *Disease Outbreaks ; Drug Resistance, Viral/*genetics ; Ebolavirus/pathogenicity ; Female ; Genotyping Techniques ; Guinea/epidemiology ; HIV Infections/*epidemiology/transmission ; HIV-1/classification/*genetics/isolation & purification ; Hemorrhagic Fever, Ebola/*epidemiology ; Humans ; Male ; Middle Aged ; Mutation ; Phylogeny ; Public Health Surveillance/methods ; Senegal/epidemiology ; }, abstract = {OBJECTIVES: Disruption in HIV care provision may enhance the development and spread of drug resistance due to inadequate antiretroviral therapy. This study thus determined the prevalence of HIV-1 transmitted drug resistance (TDR) in settings of decentralized therapy and care in Senegal and, the Ebola outbreak in Guinea. Antiretroviral-naïve patients were enrolled following a modified WHO TDR Threshold Survey method, implemented in Senegal (January-March 2015) and Guinea (August-September 2015). Plasma and dried blood spots specimens, respectively from Senegalese (n = 69) and Guinean (n = 50) patients, were collected for direct sequencing of HIV-1 pol genes. The Stanford Calibrated Population Resistance program v6.0 was used for Surveillance Drug Resistance Mutations (SDRMs).

RESULTS: Genotyping was successful from 54/69 (78.2%) and 31/50 (62.0%) isolates. In Senegal, TDR prevalence was 0% (mean duration since HIV diagnosis 4.08 ± 3.53 years). In Guinea, two patients exhibited SDRMs M184V (NRTI), T215F (TAM) and, G190A (NNRTI), respectively. TDR prevalence at this second site, however, could not be ascertained because of low sample size. Phylogenetic inference confirmed CRF02_AG predominance in Senegal (62.96%) and Guinea (77.42%). TDR prevalence in Senegal remains extremely low suggesting improved control measures. Continuous surveillance in both settings is mandatory and, should be done closest to diagnosis/transmission time and with larger sample size.}, } @article {pmid30309382, year = {2018}, author = {Wong, CKH and Siu, SC and Wong, KW and Yu, EYT and Lam, CLK}, title = {Five-year effectiveness of short messaging service (SMS) for pre-diabetes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {709}, pmid = {30309382}, issn = {1756-0500}, mesh = {Aged ; Blood Glucose/metabolism ; Blood Pressure/physiology ; Body Mass Index ; Cholesterol, HDL/blood ; Cholesterol, LDL/blood ; Female ; Humans ; Male ; Middle Aged ; Prediabetic State/blood/physiopathology/*prevention & control ; *Reminder Systems ; Retrospective Studies ; *Risk Reduction Behavior ; *Text Messaging ; Time Factors ; Treatment Outcome ; Triglycerides/blood ; }, abstract = {OBJECTIVE: An observational post-randomized controlled trial (RCT) design was adopted to evaluate the long-term sustainability and maintenance of improved glycemic control, lipid profile, reduced progression to diabetes at 3-year following a 2-year short messaging service (SMS). We performed a naturalistic follow-up to the 104 participants of SMS intervention, a 2-year randomized controlled trial comparing the SMS to non-SMS for pre-diabetes. All participants were arranged screening for diabetes at 5-year assessment. Primary outcome of this post-RCT study was cumulative incidence of diabetes whereas secondary outcomes were the change in biometric data over a 5-year period.

RESULTS: After a mean 57-month follow-up, 19 (18.3%) were lost to follow-up after the RCT period. Progression to diabetes occurred in 20 and 16 patients among the intervention and control group respectively, with no significant between-group difference (8.06 and 7.31 cases per 100 person years, respectively; Hazard Ratio in the intervention group, 1.184; 95% confidence interval, 0.612 to 2.288; p-value = 0.616). No significant effect of SMS on reduction in diabetes was observed in overall and pre-defined subgroups. The SMS intervention preserved the clinical benefits within the trial period but failed to transform from treatment efficacy to long-term effectiveness beyond 2 years after intervention. Trail registration ClinicalTrials.gov Identifier NCT01556880, retrospectively registered on March 16, 2012.}, } @article {pmid30309379, year = {2018}, author = {Hashmi, KA and Abbas, K and Hashmi, AA and Irfan, M and Edhi, MM and Ali, N and Khan, A}, title = {In-hospital mortality of patients with cardiogenic shock after acute myocardial infarction; impact of early revascularization.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {721}, pmid = {30309379}, issn = {1756-0500}, mesh = {Afghanistan ; Age Factors ; Aged ; Aged, 80 and over ; Coronary Artery Bypass/*statistics & numerical data ; Diabetes Mellitus/physiopathology ; Female ; Hospital Mortality/*trends ; Hospitals ; Humans ; Hypertension/physiopathology ; Male ; Middle Aged ; Myocardial Infarction/complications/*mortality/pathology/surgery ; Myocardial Revascularization/*statistics & numerical data ; Obesity/physiopathology ; Risk Factors ; Shock, Cardiogenic/complications/*mortality/pathology/surgery ; Thrombolytic Therapy/*statistics & numerical data ; }, abstract = {OBJECTIVES: The purpose of this study was to determine the frequency of in-hospital mortality in 351 patients who developed cardiogenic shock after acute myocardial infarction and by determining this; we might find that how efficiently we could manage this serious condition in our population by knowing the factors which are associated with high mortality after cardiogenic shock. Moreover impact of early revascularization like thrombolytic therapy or angioplasty was also evaluated.

RESULTS: Mean age was 65.41 ± 7.78 years in our study. In-hospital mortality with cardiogenic shock after acute myocardial infarction was found to be 44.73%. Significant association of in-hospital mortality was noted with age, hypertension, diabetes mellitus and BMI. Patients receiving early revascularization were noted to have lower in-hospital mortality compared to those in whom revascularization was not done due to delayed presentation. This study concluded that there is a high frequency (44.73%) of in-hospital mortality in patients with cardiogenic shock after acute myocardial in our population. So, we recommend that for achieving a good outcome and to reduce in-hospital mortality; in addition to rapid diagnosis of this condition, underlying risk factors like hypertension and diabetes should be evaluated and managed accordingly and early revascularization should be done when possible.}, } @article {pmid30309374, year = {2018}, author = {Hoppe, S and Breves, G and Klinger, S}, title = {Calcium-induced chloride secretion is decreased by Resveratrol in ileal porcine tissue.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {719}, pmid = {30309374}, issn = {1756-0500}, support = {KL 2882/2-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Calcium Chloride/*pharmacology ; Carbachol/pharmacology ; Chlorides/*metabolism ; Cyclic AMP/metabolism ; Cystic Fibrosis Transmembrane Conductance Regulator/*metabolism ; Diffusion Chambers, Culture ; Electric Conductivity ; Ileum/*drug effects/metabolism ; Ion Transport ; Jejunum/drug effects/metabolism ; Organ Specificity ; Resveratrol/*pharmacology ; Swine ; Tissue Culture Techniques ; }, abstract = {OBJECTIVE: Chloride (Cl-) secretion is crucial for intestinal fluid secretion. Therefore, effects of the polyphenol Resveratrol (RSV) on Cl- secretion have been investigated. In a previous study, we observed effects of RSV on forskolin-induced Cl- secretion in the porcine jejunum but not the ileum although RSV itself induced a transepithelial ion current that may represent Cl- secretion in the ileum. The aim of this study was to gain further insights regarding the effects of RSV on characteristics of Cl- secretion in the porcine ileum using the Ussing chamber technique (recording of short circuit currents (Isc) as a measure for epithelial net ion transfer).

RESULTS: RSV increased the Isc in the porcine ileum but not in the porcine jejunum as is already known. This increase was absent in a Cl--free buffer system, indicating that RSV indeed induces Cl- secretion. However, the carbachol-induced Isc was significantly inhibited by RSV indicating an inhibition of Ca2+-induced Cl- secretion. The cellular basis for these contradictory, segment specific results of RSV on Cl- secretion has to be subjected to further studies. The results also underline, that is difficult to generalize effects of RSV between different intestinal locations, organs, cell culture models or species.}, } @article {pmid30309354, year = {2018}, author = {Bhaduri, A and Nowakowski, TJ and Pollen, AA and Kriegstein, AR}, title = {Identification of cell types in a mouse brain single-cell atlas using low sampling coverage.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {113}, pmid = {30309354}, issn = {1741-7007}, support = {F32 NS103266/NS/NINDS NIH HHS/United States ; U01 MH105989/MH/NIMH NIH HHS/United States ; }, abstract = {BACKGROUND: High throughput methods for profiling the transcriptomes of single cells have recently emerged as transformative approaches for large-scale population surveys of cellular diversity in heterogeneous primary tissues. However, the efficient generation of such atlases will depend on sufficient sampling of diverse cell types while remaining cost-effective to enable a comprehensive examination of organs, developmental stages, and individuals.

RESULTS: To examine the relationship between sampled cell numbers and transcriptional heterogeneity in the context of unbiased cell type classification, we explored the population structure of a publicly available 1.3 million cell dataset from E18.5 mouse brain and validated our findings in published data from adult mice. We propose a computational framework for inferring the saturation point of cluster discovery in a single-cell mRNA-seq experiment, centered around cluster preservation in downsampled datasets. In addition, we introduce a "complexity index," which characterizes the heterogeneity of cells in a given dataset. Using Cajal-Retzius cells as an example of a limited complexity dataset, we explored whether the detected biological distinctions relate to technical clustering. Surprisingly, we found that clustering distinctions carrying biologically interpretable meaning are achieved with far fewer cells than the originally sampled, though technical saturation of rare populations such as Cajal-Retzius cells is not achieved. We additionally validated these findings with a recently published atlas of cell types across mouse organs and again find using subsampling that a much smaller number of cells recapitulates the cluster distinctions of the complete dataset.

CONCLUSIONS: Together, these findings suggest that most of the biologically interpretable cell types from the 1.3 million cell database can be recapitulated by analyzing 50,000 randomly selected cells, indicating that instead of profiling few individuals at high "cellular coverage," cell atlas studies may instead benefit from profiling more individuals, or many time points at lower cellular coverage and then further enriching for populations of interest. This strategy is ideal for scenarios where cost and time are limited, though extremely rare populations of interest (< 1%) may be identifiable only with much higher cell numbers.}, } @article {pmid30309345, year = {2018}, author = {Ptatscheck, C and Milne, PC and Traunspurger, W}, title = {Is stemflow a vector for the transport of small metazoans from tree surfaces down to soil?.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {43}, pmid = {30309345}, issn = {1472-6785}, abstract = {BACKGROUND: Stemflow is an essential hydrologic process shaping the soil of forests by providing a concentrated input of rainwater and solutions. However, the transport of metazoans by stemflow has yet to be investigated. This 8-week study documented the organisms (< 2 mm) present in the stemflow of different tree species. Because the texture of the tree bark is a crucial determination of stemflow, trees with smooth bark (Carpinus betulus and Fagus sylvatica) and rough bark (Quercus robur) were examined.

RESULTS: Up to 1170 individuals per liter of stemflow were collected. For rotifers and nematodes, a highly positive correlation between abundance and stemflow yield was determined. Both taxa were predominant (rotifers: up to 70%, nematodes: up to 13.5%) in the stemflow of smooth-barked trees whereas in that of the oak trees collembolans were the most abundant organisms (77.3%). The mean number of organisms collected per liter of stemflow from the two species of smooth-barked trees was very similar. A higher number of nematode species was found in the stemflow of these trees than in the stemflow of rough-barked oak and all were typical colonizers of soil- and bark-associated habitats.

CONCLUSION: This pilot study showed for the first time that stemflow is a transport vector for numerous small metazoans. By connecting tree habitats (e.g., bark, moss, lichens or water-filled tree holes) with soil, stemflow may influence the composition of soil fauna by mediating intensive organismal dispersal.}, } @article {pmid30309340, year = {2018}, author = {Deng, L and Wang, J and Xiao, Y and Wang, Z and Liu, H}, title = {Accurate prediction of protein-lncRNA interactions by diffusion and HeteSim features across heterogeneous network.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {370}, pmid = {30309340}, issn = {1471-2105}, support = {61672541//National Natural Science Foundation of China/ ; 61672113//National Natural Science Foundation of China/ ; 2017JJ3287//Natural Science Foundation of Hunan Province/ ; }, mesh = {Computer Simulation ; Databases, Genetic ; *Neural Networks (Computer) ; RNA, Long Noncoding/*genetics ; RNA-Binding Proteins/genetics ; }, abstract = {BACKGROUND: Identifying the interactions between proteins and long non-coding RNAs (lncRNAs) is of great importance to decipher the functional mechanisms of lncRNAs. However, current experimental techniques for detection of lncRNA-protein interactions are limited and inefficient. Many methods have been proposed to predict protein-lncRNA interactions, but few studies make use of the topological information of heterogenous biological networks associated with the lncRNAs.

RESULTS: In this work, we propose a novel approach, PLIPCOM, using two groups of network features to detect protein-lncRNA interactions. In particular, diffusion features and HeteSim features are extracted from protein-lncRNA heterogenous network, and then combined to build the prediction model using the Gradient Tree Boosting (GTB) algorithm. Our study highlights that the topological features of the heterogeneous network are crucial for predicting protein-lncRNA interactions. The cross-validation experiments on the benchmark dataset show that PLIPCOM method substantially outperformed previous state-of-the-art approaches in predicting protein-lncRNA interactions. We also prove the robustness of the proposed method on three unbalanced data sets. Moreover, our case studies demonstrate that our method is effective and reliable in predicting the interactions between lncRNAs and proteins.

AVAILABILITY: The source code and supporting files are publicly available at: http://denglab.org/PLIPCOM/ .}, } @article {pmid30309336, year = {2018}, author = {Dechow, CD and Liu, WS}, title = {DNA methylation patterns in peripheral blood mononuclear cells from Holstein cattle with variable milk yield.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {744}, pmid = {30309336}, issn = {1471-2164}, support = {2008-34437-19335//Cooperative State Research, Education, and Extension Service/ ; }, mesh = {Animals ; Cattle ; *DNA Methylation ; Genomics ; Leukocytes, Mononuclear/*metabolism ; Milk/*metabolism ; Phenotype ; }, abstract = {BACKGROUND: Milk yield for Holstein cows has doubled over five decades due to genetic selection and changes to management, but the molecular mechanisms that facilitated this increase are mostly unknown. Epigenetic modifications to the cattle genome are a plausible molecular mechanism to cause variation in milk yield and our objective was to describe genome-wide DNA methylation patterns in peripheral blood mononuclear cells (PBMC) from mature Holstein dairy cows with variable milk yield.

RESULTS: Whole genome MeDIP-seq was performed following DNA extraction from PBMC of 6 lactating dairy cows from 4 different herds that varied in milk yield from 13,556 kg to 23,105 kg per 305 day lactation. We describe methylation across the genome and for 13,677 protein coding genes. Repetitive element reads were primarily mapped to satellite (36.4%), SINE (29.1%), and LINE (23.7%) regions and the majority (78.4%) of CpG sites were sequenced at least once. DNA methylation was generally low upstream of genes with the nadir occurring 95 bp prior to the transcription start site (TSS). Methylation was lower in the first exon than in later exons, was highest for introns near the intron-exon junctions, and declined downstream as the distance from the gene increased. We identified 72 differentially methylated regions (DMR) between high milk yield cows and their control, and 252 DMR across herd environments.

CONCLUSIONS: This reference methylome for cattle with extreme variation in milk yield phenotype provides a resource to more fully evaluate relationships between DNA methylation and phenotype in populations subject to selection. The detection of DMR in cows of varying milk yield suggests potential to exploit epigenetic variation in cattle improvement programs.}, } @article {pmid30309330, year = {2018}, author = {Qian, W and Xiao, B and Wang, L and Hao, X and Yue, C and Cao, H and Wang, Y and Li, N and Yu, Y and Zeng, J and Yang, Y and Wang, X}, title = {CsINV5, a tea vacuolar invertase gene enhances cold tolerance in transgenic Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {228}, pmid = {30309330}, issn = {1471-2229}, support = {31770735//National Natural Science Foundation of China/ ; CARS-19//Earmarked Fund for China Agriculture Research System/ ; CAAS-ASTIP-2014-TRICAAS//Chinese Academy of Agricultural Sciences through an Innovation Project for Agricultural Sciences and Technology/ ; 2016QNRC001//Young Elite Scientist Sponsorship Program by CAST/ ; 31800588//Young Scientists Fund/ ; }, mesh = {Arabidopsis/genetics/*metabolism ; Cold Temperature ; Gene Expression Regulation, Plant ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified/genetics/*metabolism ; Tea/*enzymology ; beta-Fructofuranosidase/genetics/*metabolism ; }, abstract = {BACKGROUND: Vacuolar invertases (VINs) have been reported to regulate plant growth and development and respond to abiotic stresses such as drought and cold. With our best knowledge, the functions of VIN genes little have been reported in tea plant (Camellia sinensis L.). Therefore, it is necessary to develop research in this field.

RESULTS: Here, we identified a VIN gene, CsINV5, which was induced by cold acclimation and sugar treatments in the tea plant. Histochemical assays results showed that the 1154 bp 5'-flanking sequence of CsINV5 drove β-glucuronidase (GUS) gene expression in roots, stems, leaves, flowers and siliques of transgenic Arabidopsis during different developmental stages. Moreover, promoter deletion analysis results revealed that an LTRE-related motif (CCGAAA) and a WBOXHVISO1 motif (TGACT) within the promoter region of CsINV5 were the core cis-elements in response to low temperature and sugar signaling, respectively. In addition, overexpression of CsINV5 in Arabidopsis promoted taproot and lateral root elongation through glucose-mediated effects on auxin signaling. Based on physiological and RNA-seq analysis, we found that overexpression of CsINV5 improved cold tolerance in transgenic Arabidopsis mainly by increasing the contents of glucose and fructose, the corresponding ratio of hexose to sucrose, and the transcription of osmotic-stress-related genes (P5CS1, P5CS2, AtLEA3, COR413-PM1 and COR15B) to adjust its osmotic potential.

CONCLUSIONS: Comprehensive experimental results suggest that overexpression of CsINV5 may enhance the cold tolerance of plant through the modification of cellular sugar compounds contents and osmotic regulation related pathways.}, } @article {pmid30309323, year = {2018}, author = {Zi, C and Zeng, D and Ling, N and Dai, J and Xue, F and Jiang, Y and Li, B}, title = {An improved assay for rapid detection of viable Staphylococcus aureus cells by incorporating surfactant and PMA treatments in qPCR.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {132}, pmid = {30309323}, issn = {1471-2180}, support = {2017YFF0208600//This study was funded by the National Key Research and Development Program of China (2017YFF0208600), The National "Youth Top-notch Talent" Support Program (W0270187), Introduction of Nanjing Agricultural University Scientific Research Grants Project (804121), AQSIQ Research Projects (2017KJ46), Central Guidance for Local Science and Technology Development (No. YDZX20173100004528), Science and Technology Joint Project of the Yangzte River Delta (No.17395810102), Jiangsu Collaborative Innovation Center of Meat Production and Processing/ ; }, abstract = {BACKGROUND: Staphylococcus aureus is an important human pathogen causing a variety of life-threatening diseases. Rapid and accurate detection of Staphylococcus aureus is a necessity for prevention of outbreaks caused by this pathogen. PCR is a useful tool for rapid detection of foodborne pathogens, however, its inability to differentiate DNA from dead cells and live cells in amplification severely limits its application in pathogen detection. The aim of this study was to develop an improved assay was developed by incorporating the sample treatments with a surfactant and propidium monoazide (PMA) in qPCR for detection of viable S. aureus cells.

RESULTS: The cell toxic effect testing with the two surfactants showed that the viability of S. aureus was virtually not affected by the treatment with 0.5% triton x-100 or 0.025% sarkosyl. Triton x-100 was coupled with PMA for sample treatments for detection of viable S. aureus cells in artificially contaminated milk. The qPCR results indicated that the assay reached high an amplification efficiency of 98.44% and the live S. aureus cells were accurately detected from the triton-treated spiked milk samples by the PMA-qPCR assay.

CONCLUSIONS: The qPCR assay combined with treatments of PMA and surfactants offers a sensitive and accurate means for detection of viable S. aureus cells. Cell toxic effect testing with the two surfactants showed that the viability of S. aureus was virtually not affected by the treatment with 0.5% triton x-100 or 0.025% sarkosyl. The information on sample treatment with surfactants to improve the dead cell DNA removal efficiency in qPCR by increasing PMA's permeability to dead cells can be used for other pathogens, especially for Gram-positive bacteria.}, } @article {pmid30309320, year = {2018}, author = {Geshnizjani, N and Ghaderi-Far, F and Willems, LAJ and Hilhorst, HWM and Ligterink, W}, title = {Characterization of and genetic variation for tomato seed thermo-inhibition and thermo-dormancy.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {229}, pmid = {30309320}, issn = {1471-2229}, mesh = {Abscisic Acid/metabolism ; Gene Expression Regulation, Plant/genetics/physiology ; Gibberellins/metabolism ; Lycopersicon esculentum/genetics/*metabolism/*physiology ; Plant Dormancy/genetics/physiology ; Quantitative Trait Loci/genetics ; Seeds/genetics/metabolism/physiology ; Solanum/genetics/*metabolism/*physiology ; }, abstract = {BACKGROUND: Exposing imbibed seeds to high temperatures may lead to either thermo-inhibition of germination or thermo-dormancy responses. In thermo-inhibition, seed germination is inhibited but quickly resumed when temperatures are lowered. Upon prolonged exposure to elevated temperatures, thermo-dormancy may be induced and seeds are not able to germinate even at optimal temperatures. In order to explore underlying physiological and molecular aspects of thermo-induced secondary dormancy, we have investigated the physiological responses of tomato seeds to elevated temperatures and the molecular mechanisms that could explain the performance of tomato seeds at elevated temperature.

RESULTS: In order to investigate how tomato seeds respond to high temperature we used two distinct tomato accessions: Solanum lycopersicum (cv. Moneymaker) (MM) and Solanum pimpinellifolium accession CGN14498 (PI). MM seeds did not germinate under high temperature conditions while seeds of PI reached a maximum germination of 80%. Despite the high germination percentage of PI, germinated seeds did not produce healthy seedling at 37 °C. By using a candidate gene approach we have tested if similar molecular pathways (abscisic acid (ABA) and gibberellic acid (GA)) present in lettuce and Arabidopsis, are regulating thermo-inhibition and thermo-dormancy responses in tomato. We showed that the ABA biosynthesis pathway genes NCED1 and NCED9 were upregulated whereas two of the GA-biosynthesis regulators (GA3ox1 and GA20ox1) were downregulated in tomato thermo-dormant seeds at elevated temperature. To identify novel regulators of tomato seed performance under high temperature, we screened a Recombinant Inbred Line (RIL) population derived from a cross between the two tomato accessions MM and PI for thermo-inhibition and dormancy induction. Several QTLs were detected, particularly for thermo-dormancy, which may be caused by new regulators of thermo-inhibition and thermo-dormancy in tomato.

CONCLUSIONS: None of the genes studied in this research were co-locating with the detected QTLs. The new QTLs discovered in this study will therefore be useful to further elucidate the molecular mechanisms underlying the responses of tomato seeds to high temperature and eventually lead to identification of the causal genes regulating these responses.}, } @article {pmid30309317, year = {2018}, author = {Bouhaddani, SE and Uh, HW and Jongbloed, G and Hayward, C and Klarić, L and Kiełbasa, SM and Houwing-Duistermaat, J}, title = {Integrating omics datasets with the OmicsPLS package.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {371}, pmid = {30309317}, issn = {1471-2105}, support = {MC_PC_U127561128//Medical Research Council/United Kingdom ; 305280//European Union's Seventh Framework Programme/ ; }, mesh = {Genomics/*methods ; Humans ; Least-Squares Analysis ; Metabolomics/*methods ; Software ; }, abstract = {BACKGROUND: With the exponential growth in available biomedical data, there is a need for data integration methods that can extract information about relationships between the data sets. However, these data sets might have very different characteristics. For interpretable results, data-specific variation needs to be quantified. For this task, Two-way Orthogonal Partial Least Squares (O2PLS) has been proposed. To facilitate application and development of the methodology, free and open-source software is required. However, this is not the case with O2PLS.

RESULTS: We introduce OmicsPLS, an open-source implementation of the O2PLS method in R. It can handle both low- and high-dimensional datasets efficiently. Generic methods for inspecting and visualizing results are implemented. Both a standard and faster alternative cross-validation methods are available to determine the number of components. A simulation study shows good performance of OmicsPLS compared to alternatives, in terms of accuracy and CPU runtime. We demonstrate OmicsPLS by integrating genetic and glycomic data.

CONCLUSIONS: We propose the OmicsPLS R package: a free and open-source implementation of O2PLS for statistical data integration. OmicsPLS is available at https://cran.r-project.org/package=OmicsPLS and can be installed in R via install.packages("OmicsPLS").}, } @article {pmid30309315, year = {2018}, author = {Lamara, M and Parent, GJ and Giguère, I and Beaulieu, J and Bousquet, J and MacKay, JJ}, title = {Association genetics of acetophenone defence against spruce budworm in mature white spruce.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {231}, pmid = {30309315}, issn = {1471-2229}, mesh = {Acetophenones/*metabolism ; Animals ; Moths/*pathogenicity ; Phenol ; Picea/genetics/*metabolism/*parasitology ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: Outbreaks of spruce budworm (SBW, Choristoneura fumiferana Clem.) cause major recurrent damage in boreal conifers such as white spruce (Picea glauca [Moench] Voss) and large losses of forest biomass in North America. Although defensive phenolic compounds have recently been linked to chemical resistance against SBW, their genetic basis remains poorly understood in forest trees, especially in conifers. Here, we used diverse association genetics approaches to discover genes and their variants that may control the accumulation of acetophenones, and dissect the genetic architecture of these defence compounds against SBW in white spruce mature trees.

RESULTS: Out of 4747 single nucleotide polymorphisms (SNPs) from 2312 genes genotyped in a population of 211 unrelated individuals, genetic association analyses identified 35 SNPs in 33 different genes that were significantly associated with the defence traits by using single-locus, multi-locus and multi-trait approaches. The multi-locus approach was particularly effective at detecting SNP-trait associations that explained a large fraction of the phenotypic variance (from 20 to 43%). Significant genes were regulatory including the NAC transcription factor, or they were involved in carbohydrate metabolism, falling into the binding, catalytic or transporter activity functional classes. Most of them were highly expressed in foliage. Weak positive phenotypic correlations were observed between defence and growth traits, indicating little or no evidence of defence-growth trade-offs.

CONCLUSIONS: This study provides new insights on the genetic architecture of tree defence traits, contributing to our understanding of the physiology of resistance mechanisms to biotic factors and providing a basis for the genetic improvement of the constitutive defence of white spruce against SBW.}, } @article {pmid30309314, year = {2018}, author = {Gadissa, F and Tesfaye, K and Dagne, K and Geleta, M}, title = {Genetic diversity and population structure analyses of Plectranthus edulis (Vatke) Agnew collections from diverse agro-ecologies in Ethiopia using newly developed EST-SSRs marker system.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {92}, pmid = {30309314}, issn = {1471-2156}, abstract = {BACKGROUND: Plectranthus edulis (Vatke) Agnew (locally known as Ethiopian dinich or Ethiopian potato) is one of the most economically important edible tuber crops indigenous to Ethiopia. Evaluating the extent of genetic diversity within and among populations is one of the first and most important steps in breeding and conservation measures. Hence, this study was aimed at evaluating the genetic diversity and population structure of this crop using collections from diverse agro-ecologies in Ethiopia.

RESULTS: Twenty polymorphic expressed sequence tag based simple sequence repeat (EST-SSRs) markers were developed for P. edulis based on EST sequences of P. barbatus deposited in the GenBank. These markers were used for genetic diversity analyses of 287 individual plants representing 12 populations, and a total of 128 alleles were identified across the entire loci and populations. Different parameters were used to estimate the genetic diversity within populations; and gene diversity index (GD) ranged from 0.31 to 0.39 with overall mean of 0.35. Hierarchical analysis of molecular variance (AMOVA) showed significant but low population differentiation with only 3% of the total variation accounted for variation among populations. Likewise, cluster and STRUCTURE analyses did not group the populations into sharply distinct clusters, which could be attributed to historical and contemporary gene flow and the reproductive biology of the crop.

CONCLUSIONS: These newly developed EST-SSR markers are highly polymorphic within P. edulis and hence are valuable genetic tools that can be used to evaluate the extent of genetic diversity and population structure of not only P. edulis but also various other species within the Lamiaceae family. Among the 12 populations studied, populations collected from Wenbera, Awi and Wolaita showed a higher genetic diversity as compared to other populations, and hence these areas can be considered as hot spots for in-situ conservation as well as for identification of genotypes that can be used in breeding programs.}, } @article {pmid30308280, year = {2019}, author = {O'Hara, TD and Hugall, AF and Cisternas, PA and Boissin, E and Bribiesca-Contreras, G and Sellanes, J and Paulay, G and Byrne, M}, title = {Phylogenomics, life history and morphological evolution of ophiocomid brittlestars.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {67-80}, doi = {10.1016/j.ympev.2018.10.003}, pmid = {30308280}, issn = {1095-9513}, abstract = {Brittlestars in the family Ophiocomidae are large and colourful inhabitants of tropical shallow water habitats across the globe. Here we use targeted capture and next-generation sequencing to generate robust phylogenomic trees for 39 of the 43 species in order to test the monophyly of existing genera. The large genus Ophiocoma, as currently constituted, is paraphyletic on our trees and required revision. Four genera are recognised herein: an expanded Ophiomastix (now including Ophiocoma wendtii, O. occidentalis, O. endeani, O. macroplaca, and Ophiarthrum spp), Ophiocomella (now including the non-fissiparous Ophiocoma pumila, aethiops and valenciae) and Breviturma (now including Ophiocoma pica, O. pusilla, O. paucigranulata and O. longispina) and a restricted Ophiocoma. The resulting junior homonym Ophiomastix elegans is renamed O. brocki. The genus Ophiomastix exhibits relatively high rates of morphological disparity compared to other lineages. Ophiomastix flaccida and O. (formerly Ophiarthrum) pictum have divergent mitochondrial genomes, characterised by gene-order rearrangements, strand recoding, enriched GT base composition, and a corresponding divergence of nuclear mitochondrial protein genes. The new phylogeny indicates that larval and developmental transitions occurred rarely. Larval culture trials show that species with abbreviated lecithotrophic larval development occur only within Ophiomastix, although the possible monophyly of these species is obscured by the rapid early radiation within this genus. Asexual reproduction by fission is limited to one species-complex within Ophiocomella, also characterised by elevated levels of allelic heterozygosity, and which has achieved a relatively rapid global distribution. The crown ages of the new genera considerably predate the closure of the Tethyan seaway and all four are distributed in both the Atlantic and Indo-Pacific Oceans. Two species pairs appear to reflect the closure of the Panama Seaway, although their fossil-calibrated node ages (12-14 ± 6 my), derived from both concatenated sequence and multispecies coalescent analyses, considerably predate the terminal closure event. Ophiocoma erinaceus has crossed the East Pacific barrier and is recorded from Clipperton Island, SW of Mexico.}, } @article {pmid30308279, year = {2019}, author = {Vakati, V and Eyun, SI and Lee, W}, title = {Unraveling the intricate biodiversity of the benthic harpacticoid genus Nannopus (Copepoda, Harpacticoida, Nannopodidae) in Korean waters.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {366-379}, doi = {10.1016/j.ympev.2018.10.004}, pmid = {30308279}, issn = {1095-9513}, abstract = {Nannopus (Harpacticoida, Nannopodidae) species are abundant and widely distributed throughout the world across a variety of habitats. Nannopus is well known for high frequencies of misidentifications and thus may comprise several cryptic complexes and morphologically distinct species. Cryptic taxa are common in meiofauna communities. In this study, we aimed to identify Nannopus species using an integrative approach including molecular taxonomy. We adopted a non-destructive DNA extraction method so that morphological and molecular data could be obtained from the same specimen. We analyzed the molecular diversity and distributions of Nannopus using a total of 190 individuals. We sequenced the 190 mtCOI, 53 mtCYTB, 25 18SrDNA, and 43 28SrDNA genes from 190 individuals. Several species delimitation approaches were applied, including uncorrected p-distances for mtCOI, mtCYTB, 18SrDNA, and 28SrDNA, and Automatic Barcode Gap Discovery and Bayesian implemented Poisson tree processes for mtCOI and mtCYTB data. The maximum likelihood and Bayesian approaches were used to examine the phylogenetic relationships among individuals using the combined set of all four genes. Our species delimitation and phylogenetic analyses indicated the presence of three cryptic and six morphologically distinct species. All species are sympatric and widely distributed across mudflats ranging from the Yellow Sea to the South Sea in Korea. The divergence patterns of the four genes were not congruent. A phylogenetic tree based on the concatenated dataset was the most robust, was congruent with morphology, and suggested two major clades. We considered the validity of reinstating the genus Ilyophilus (Lilljeborg, 1902) and ultimately concluded that including all congeners in Nannopus until the type species (N. palustris Brady, 1880) is re-described was the most prudent approach.}, } @article {pmid30308278, year = {2019}, author = {Huang, XC and Su, JH and Ouyang, JX and Ouyang, S and Zhou, CH and Wu, XP}, title = {Towards a global phylogeny of freshwater mussels (Bivalvia: Unionida): Species delimitation of Chinese taxa, mitochondrial phylogenomics, and diversification patterns.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {45-59}, doi = {10.1016/j.ympev.2018.09.019}, pmid = {30308278}, issn = {1095-9513}, abstract = {The Yangtze River Basin in China is one of the global hotspots of freshwater mussel (order Unionida) diversity with 68 nominal species. Few studies have tested the validity of these nominal species. Some taxa from the Yangtze unionid fauna have not been adequately examined using molecular data and well-positioned phylogenetically with respect to the global Unionida. We evaluated species boundaries of Chinese freshwater mussels, and disentangled their phylogenetic relationships within the context of the global freshwater mussels based on the multi-locus data and complete mitochondrial genomes. Moreover, we produced the time-calibrated phylogeny of Unionida and explored patterns of diversification. COI barcode data suggested the existence of 41 phylogenetic distinct species from our sampled 40 nominal taxa inhabiting the middle and lower reaches of the Yangtze River. Maximum likelihood and Bayesian inference analyses on three loci (COI, 16S, and 28S) and complete mitochondrial genomes showed that the subfamily Unioninae sensu stricto was paraphyletic, and the subfamily Anodontinae should be subsumed under Unioninae. In addition, we described two new tribes (Aculamprotulini tribe nov. and Lepidodesmini tribe nov.) in the subfamily Unioninae and one new genus (Parvasolenaiagen. nov.) in the subfamily Gonideinae. Molecular dating analysis suggested freshwater mussels diversified at 346.1 Mya (HPD = 286.6-409.9). The global diversification rate for Unionida was estimated to be 0.025 species/Myr. Our study found only a single well-supported rate shift in Unionida diversification, occurring at the base of the subfamily Ambleminae. The evolution of active host-attraction may have triggered the burst of speciation in Ambleminae, and the environment and geography of the Mississippi River Basin likely sustained this radiation.}, } @article {pmid30308248, year = {2018}, author = {Hessler, T and Harrison, STL and Huddy, RJ}, title = {Stratification of microbial communities throughout a biological sulphate reducing up-flow anaerobic packed bed reactor, revealed through 16S metagenomics.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {543-551}, doi = {10.1016/j.resmic.2018.09.003}, pmid = {30308248}, issn = {1769-7123}, mesh = {Anaerobiosis ; Bacteria/classification/*genetics/isolation & purification/*metabolism ; Biodegradation, Environmental ; Biodiversity ; Bioreactors/*microbiology ; DNA, Bacterial/genetics ; Genome, Bacterial ; Metagenomics ; Oxidation-Reduction ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sulfur Compounds/*metabolism ; }, abstract = {Biological sulphate reduction (BSR) is a promising low-cost treatment of acid rock drainage effluents. In this paper, the system performance and microbial ecology of a lactate supplemented BSR up-flow anaerobic packed bed reactor (UAPBR) are evaluated across reactor height and compared to a continuous stirred tank reactor (CSTR). The biomass concentrations of planktonic and biofilm communities were quantified and subsequently characterised by 16S rRNA gene amplicon sequencing. The defined microbial communities were shown to correlate with differing availability of lactate, volatile fatty acids produced from lactate degradation and sulphate concentration. The UAPBR was able to achieve near complete sulphate conversion at a 4-day hydraulic residence time (HRT) at a sulphate feed concentration of 10.41 mM (1 g/L). The high volumetric sulphate reduction rate of 0.184 mM/L.h achieved in the first third of the reactor was attributed to OTUs present in the planktonic and biofilm communities. While the scavenging of sulphate within the final third of the UAPBR was attributed to an acetate oxidising genus of SRB which was not detected in the lactate-fed CSTR. The detailed analyses of the microbial communities throughout the UAPBR and CSTR contribute to the growing understanding of the impact of the microbial communities of BSR reactors on system performance.}, } @article {pmid30307541, year = {2018}, author = {Saito, Y and Sato, T and Nomoto, K and Tsuji, H}, title = {Erratum: Identification of phenol- and p-cresol-producing intestinal bacteria by using media supplemented with tyrosine and its metabolites.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy206}, pmid = {30307541}, issn = {1574-6941}, } @article {pmid30307390, year = {2018}, author = {Arroua, B and Grimaud, R and Hirschler-Réa, A and Bouriat, P and Magot, M and Urios, L and Ranchou-Peyruse, A}, title = {Pleomorphochaeta naphthae sp. nov., a new anaerobic fermentative bacterium isolated from an oil field.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3747-3753}, doi = {10.1099/ijsem.0.003048}, pmid = {30307390}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Congo ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Oil and Gas Fields/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spirochaetaceae/*classification/genetics/isolation & purification ; }, abstract = {A novel anaerobic fermentative bacterium, strain SEBR 4209T, was isolated from a water sample of a Congolese oil field. Strain SEBR 4209T is phylogenetically related to the genus Pleomorphochaeta, in the family Spirochaetaceae. Its closest relatives are Pleomorphochaeta caudata SEBR 4223T (94.5 % 16S rRNA gene sequence similarity) and Pleomorphochaeta multiformis MO-SPC2T (94.3 % similarity). Like the other members of this genus, cells have a pleomorphic morphology, in particular an annular shape and long stalks. Optimal growth was observed at 37 °C, at pH between 6.8 and 7.0, and with 40 g l-1 NaCl. This strain was only able to grow by fermentation of carbohydrates. The fermentation products from glucose utilization were acetate, ethanol, CO2 and H2. Predominant fatty acids were C14 : 0, C14 : 0 DMA, C16 : 0 and C16 : 1ω7c. The major polar lipids were phosphoglycolipids, phospholipids and glycolipids. The G+C content of the DNA was 29.6 mol%. Based on phenotypic characteristics and phylogenetic traits, strain SEBR 4209T is considered to represent a novel species of the genus Pleomorphochaeta, for which the name Pleomorphochaetanaphthae sp. nov. is proposed. The type strain is SEBR 4209T (=DSM 104684T=JCM 31871T).}, } @article {pmid30307389, year = {2018}, author = {Zhang, LL and Gan, LZ and Xu, ZB and Yang, F and Li, Y and Fan, XL and Liu, XF and Tian, YQ and Dai, YM}, title = {Pedobacter chitinilyticus sp. nov., a chitin-degrading bacterium isolated from wheat leaf tissue.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3713-3719}, doi = {10.1099/ijsem.0.003017}, pmid = {30307389}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Chitin/metabolism ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Pedobacter/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; Plant Leaves/microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Triticum/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A bacterium, designated strain CM134L-2T, was isolated from a chitin-enriched wheat leaf microbiome in Chengdu, Sichuan province, China. It was Gram-stain-negative, strictly aerobic, non-spore-forming, motile, rod-shaped, and bright yellow in colour. Strain CM134L-2T grew at 4-35 °C, at pH 6.0-9.0 and could use chitin as the only carbon resource. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CM134L-2T was most closely related to Pedobacter nanyangensis Q-4T (97.7 %) and Pedobacter zeaxanthinifaciens TDMA-5T (97.4 %). Digital DNA-DNA hybridization (dDDH) values between strain CM134L-2T with these two type strains were 26.8 and 20.8 %, respectively, and average nucleotide identity (ANI) values were 83.2 and 76.2 %; these values are lower than the proposed and generally accepted species boundaries of 70 % for dDDH and 95-96 % for ANI, which suggests strain CM134L-2T represents a novel species. The genomic DNA G+C content of strain CM134L-2T was 39.3 mol%, menaquinone-7 was the major respiratory quinone, phosphatidylethanolamine was the major polar lipid and the major components of the cellular fatty acids were iso-C15 : 0, and C16 : 1ω7c/C16 : 1ω6c (summed feature 3); these features supported the affiliation of strain CM134L-2T to the genus Pedobacter. Overall, strain CM134L-2T belongs to the genus Pedobacter, but can be classified as a novel species, for which the name Pedobacter chitinilyticus sp. nov. is proposed. The type strain is CM134L-2T (=CGMCC 1.16520T=KCTC 62643T).}, } @article {pmid30307388, year = {2018}, author = {Wu, M and Zong, Y and Guo, W and Wang, G and Li, M}, title = {Paenibacillus montanisoli sp. nov., isolated from mountain area soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3569-3575}, doi = {10.1099/ijsem.0.003036}, pmid = {30307388}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Genes, Bacterial ; Nucleic Acid Hybridization ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, motile, endospore-forming and rod-shaped bacterium, designated RA17T, was isolated from Dafan, Hubei Province, China. Based on 16S rRNA gene sequence similarity comparisons, strain RA17T was most closely related to Paenibacillus taihuensis THMBG22T (97.4 %), Paenibacillus rhizoryzae ACCC 1ZS3-5T (97.4 %) and Paenibacillus sacheonensis DSM SY01T (96.5 %). Analysis of the rpoB gene also indicated that RA17T had the highest similarity to P. rhizoryzae ACCC 1ZS3-5T (92.3 %), P. taihuensis THMBG22T (88.4 %) and P. sacheonensis DSM SY01T (85.5 %). The DNA-DNA hybridization values between strain RA17T and the two type strains, P. taihuensis THMBG22T and P. rhizoryzae ACCC 1ZS3-5T, were 36.8 and 22.9 %, respectively. Its genome size was 6.17 Mb, comprising 5677 predicted genes with a DNA G+C content of 52.82 mol %. The major cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphoglycolipid, four aminophospholipids, an unidentified phospholipid and an unidentified polar lipid. The major quinone was menaquinone 7. The diagnostic diamino acid of the cell wall was meso-diaminopimelic acid. The low DNA-DNA hybridization values, physiological and biochemical differences, such as growth at 4 °C, acid production from inositol, lack of α-chymotrypsin activity, no casein hydrolysis, and negative for acid production from d-fructose, melibiose and sucrose, could distinguish strain RA17T from its closely related species. Consequently, strain RA17T represents a novel species of the genus Paenibacillus, for which the name Paenibacillusmontanisoli sp. nov. is proposed, with RA17T (=KCTC 33894T=CCTCC AB 2017053T) as the type strain.}, } @article {pmid30307387, year = {2018}, author = {Diop, A and Barker, SC and Eberhard, M and Barker, D and Nguyen, TT and Di Pinto, F and Raoult, D and Mediannikov, O}, title = {Rickettsia fournieri sp. nov., a novel spotted fever group rickettsia from Argas lagenoplastis ticks in Australia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3781-3784}, doi = {10.1099/ijsem.0.003057}, pmid = {30307387}, issn = {1466-5034}, mesh = {Animals ; Argas/*microbiology ; Australia ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rickettsia/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Spotted Fever Group Rickettsiosis ; }, abstract = {Strain AUS118T was isolated from an Argas lagenoplastis tick collected from the nest of a Petrochelidon ariel (fairy martin) in Australia in 2013. Microscopic observation of infected cell cultures indicated this strain had a morphology and intracellular location typical of Rickettsiaspecies. Phylogenetic analysis of this strain based firstly on multi-locus sequence analysis and subsequently on whole genome analysis demonstrated that AUS118T was most closely related to, but divergent from Rickettsia japonica and Rickettsia heilongjiangensis. We therefore propose the creation of a novel species, Rickettsia fournieri sp. nov, with the type strain AUS118T (DSM 28985 and CSUR R501).}, } @article {pmid30307386, year = {2018}, author = {Song, L and Liu, H and Cai, S and Huang, Y and Dai, X and Zhou, Y}, title = {Alcanivorax indicus sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3785-3789}, doi = {10.1099/ijsem.0.003058}, pmid = {30307386}, issn = {1466-5034}, mesh = {Alcanivoraceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Indian Ocean ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-negative, motile, rod-shaped bacterium, designated SW127T, was isolated from a seawater sample collected from the Indian Ocean. Strain SW127T was aerobic, catalase- and oxidase-positive, and grew at 8-42 °C (optimum, 30 °C), at pH 5.5-9.0 (optimum, pH 7.5) and in the presence of 0.5-11.0 % (w/v) NaCl (optimum, 3.0-4.0 %). Comparative analysis of 16S rRNA gene sequences indicated that strain SW127T belonged to the genus Alcanivorax, and closely related to Alcanivorax pacificus MCCC 1A00474T (96.7 % sequence similarity). The predominant cellular fatty acids of strain SW127T were C16 : 0 and summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c). Strain SW127T contained phosphatidylethanolamine and phosphatidylglycerol as the major polar lipids. The genomic DNA G+C content of strain SW127T was 62.8 mol%. On the basis of its phenotypic characteristics and phylogenetic data, strain SW127T represents a novel species of the genus Alcanivorax, for which the name Alcanivorax indicus sp. nov. is proposed. The type strain is SW127T (=CGMCC 1.16233T=KCTC 62652T).}, } @article {pmid30307385, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Proposal to modify Rules 27 and 30(3)(b) of the International Code of Nomenclature of Prokaryotes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3951-3953}, doi = {10.1099/ijsem.0.003063}, pmid = {30307385}, issn = {1466-5034}, abstract = {We propose to modify Rules 27 and 30(3)(b) of the International Code of Nomenclature of Prokaryotes so that the formal description of new taxa (the 'protologue') will include a statement about the nomenclatural type, so that this information will be linked to the name of the taxon, the derivation (etymology) of the name, and the properties of the taxon.}, } @article {pmid30307384, year = {2018}, author = {Chen, RW and Wang, KX and Zhou, XF and Long, C and Tian, XP and Long, LJ}, title = {Indioceanicola profundi gen. nov., sp. nov., isolated from Indian Ocean sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3707-3712}, doi = {10.1099/ijsem.0.003016}, pmid = {30307384}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Indian Ocean ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Rhodospirillaceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A novel basophilic bacterial strain, designated as SCSIO 08040T, was recovered from a deep-sea sediment sample collected from the Indian Ocean. The strain was Gram-stain-negative, vibrioid or spiral, light pink, 0.6-1.0 µm wide and 1.0-2.5 µm long. Growth occurred at 20-45 °C, pH 7-11 and <5 % (w/v) NaCl, with optimum growth at 28-37 °C, pH 7 and 0-3 % (w/v) NaCl. Catalase-, oxidase and urease-positive, nitrate reduction-negative. Analysis of 16S rRNA gene sequencing revealed that strain SCSIO 08040T had the highest similarity of 95.3 % to Rhodocista pekingensis 3-pT. Phylogenetic analysis based on nearly complete 16S rRNA gene sequences showed that the novel isolate formed a distinct phylogenetic lineage in the family Rhodospirillaceae. The whole-cell hydrolysate contained meso-diaminopimelic acid, galactose, mannose and xylose. The total cellular fatty acid profile was dominated by C18:1ω7c and C19:0cycloω8c. Q-10 was the predominant ubiquinone. The major phospholipids were diphosphatidylglycerol, phosphatidylcholine and phosphatidylethanolamine. The DNA G+C content of strain SCSIO 08040T was 66.82 mol%. Based on these polyphasic data, a new genus, Indioceanicola gen. nov., is proposed in the family Rhodospirillaceae with the type species Indioceanicola profundi sp. nov. and the type strain SCSIO 08040T (=DSM 105146T=CGMCC 1.15812T).}, } @article {pmid30307121, year = {2018}, author = {Mukasa, Y and Kyamanywa, S and Sserumaga, JP and Otim, M and Tumuhaise, V and Erbaugh, M and Egonyu, JP}, title = {An atoxigenic L-strain of Aspergillus flavus (Eurotiales: Trichocomaceae) is pathogenic to the coffee twig borer, Xylosandrus compactus (Coleoptera: Curculionidea: Scolytinae).}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12705}, pmid = {30307121}, issn = {1758-2229}, support = {EPP-A-00-0400016-00//Integrated Pest Management Innovation Lab/ ; }, abstract = {This study isolated and evaluated virulence of fungal entomopathogens of Xylosandrus compactus - an important pest of Robusta coffee in Sub-Saharan Africa. A survey was conducted in five farming systems in Uganda to isolate entomopathogens associated with X. compactus. Four fungal isolates were screened for virulence against X. compactus in the laboratory at 1 × 107 conidia ml-1 where an atoxigenic L-strain of A. flavus killed 70%-100% of all stages of X. compactus compared with other unidentified isolates which caused 20%-70% mortalities. The time taken by A. flavus to kill 50% of X. compactus eggs, larvae, pupae and adults in the laboratory was 2-3 days; whereas the other unidentified fungal isolates took 4-7 days. The concentrations of A. flavus that killed 50% of different stages of X. compactus were 5 × 105 , 12 × 105 , 17 × 105 and 30 × 105 conidia ml-1 for larvae, eggs, pupae and adults respectively. A formulation of A. flavus in oil caused higher mortalities of X. compactus larvae, pupae and adults in the field (71%-79%) than its formulation in water (33%-47%). The atoxigenic strain of A. flavus could therefore be developed into a safe biopesticide against X. compactus.}, } @article {pmid30307107, year = {2019}, author = {Akroume, E and Maillard, F and Bach, C and Hossann, C and Brechet, C and Angeli, N and Zeller, B and Saint-André, L and Buée, M}, title = {First evidences that the ectomycorrhizal fungus Paxillus involutus mobilizes nitrogen and carbon from saprotrophic fungus necromass.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {197-208}, doi = {10.1111/1462-2920.14440}, pmid = {30307107}, issn = {1462-2920}, abstract = {Fungal succession in rotting wood shows a surprising abundance of ectomycorrhizal (EM) fungi during the late decomposition stages. To better understand the links between EM fungi and saprotrophic fungi, we investigated the potential capacities of the EM fungus Paxillus involutus to mobilize nutrients from necromass of Postia placenta, a wood rot fungus, and to transfer these elements to its host tree. In this aim, we used pure cultures of P. involutus in the presence of labelled Postia necromass (15 N/13 C) as nutrient source, and a monoxenic mycorrhized pine experiment composed of labelled Postia necromass and P. involutus culture in interaction with pine seedlings. The isotopic labelling was measured in both experiments. In pure culture, P. involutus was able to mobilize N, but C as well, from the Postia necromass. In the symbiotic interaction experiment, we measured high 15 N enrichments in all plant and fungal compartments. Interestingly, 13 C remains mainly in the mycelium and mycorrhizas, demonstrating that the EM fungus transferred essentially N from the necromass to the tree. These observations reveal that fungal organic matter could represent a significant N source for EM fungi and trees, but also a C source for mycorrhizal fungi, including in symbiotic lifestyle.}, } @article {pmid30307105, year = {2018}, author = {Chen, D and Wu, C and Hao, C and Huang, P and Liu, H and Bian, Z and Xu, JR}, title = {Sexual specific functions of Tub1 beta-tubulins require stage-specific RNA processing and expression in Fusarium graminearum.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4009-4021}, doi = {10.1111/1462-2920.14441}, pmid = {30307105}, issn = {1462-2920}, support = {//US Wheat and Barley Scab Initiative/ ; //National Science Foundation/ ; }, abstract = {The wheat head blight fungus Fusarium graminearum has two highly similar beta-tubulin genes with overlapping functions during vegetative growth but only TUB1 is important for sexual reproduction. To better understand their functional divergence during ascosporogenesis, in this study we characterized the sequence elements important for stage-specific functions of TUB1. Deletion of TUB1 blocked the late but not initial stages of perithecium formation. Perithecia formed by tub1 mutant had limited ascogenous hyphae and failed to develop asci. Silencing of TUB1 by MSUD also resulted in defects in ascospore formation. Interestingly, the 3'-UTR of TUB1 was dispensable for growth but essential for its function during sexual reproduction. RIP mutations that specifically affected Tub1 functions during sexual reproduction also were identified in two ascospore progeny. Furthermore, site-directed mutagenesis showed that whereas the non-editable mutations at three A-to-I RNA editing sites had no effects, the N347D (not T362D or I368V) edited mutation affected ascospore development. In addition, the F167Y, but not E198K or F200Y, mutation in TUB1 conferred tolerance to carbendazim and caused a minor defect in sexual reproduction. Taken together, our data indicate TUB1 plays an essential role in ascosporogenesis and sexual-specific functions of TUB1 require stage-specific RNA processing and Tub1 expression.}, } @article {pmid30307104, year = {2019}, author = {Florentino, AP and Pereira, IAC and Boeren, S and van den Born, M and Stams, AJM and Sánchez-Andrea, I}, title = {Insight into the sulfur metabolism of Desulfurella amilsii by differential proteomics.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {209-225}, doi = {10.1111/1462-2920.14442}, pmid = {30307104}, issn = {1462-2920}, support = {323009//H2020 European Research Council/ ; 024.002.002//Netherlands Ministry of Education, Culture and Science/ ; //Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Brazilian Government/ ; }, abstract = {Many questions regarding proteins involved in microbial sulfur metabolism remain unsolved. For sulfur respiration at low pH, the terminal electron acceptor is still unclear. Desulfurella amilsii is a sulfur-reducing bacterium that respires elemental sulfur (S0) or thiosulfate, and grows by S0 disproportionation. Due to its versatility, comparative studies on D. amilsii may shed light on microbial sulfur metabolism. Requirement of physical contact between cells and S0 was analyzed. Sulfide production decreased by around 50% when S0 was trapped in dialysis membranes, suggesting that contact between cells and S0 is beneficial, but not strictly needed. Proteome analysis was performed under the aforementioned conditions. A Mo-oxidoreductase suggested from genome analysis to act as sulfur reductase was not detected in any growth condition. Thiosulfate and sulfite reductases showed increased abundance in thiosulfate-reducing cultures, while rhodanese-like sulfurtransferases were highly abundant in all conditions. DsrE and DsrL were abundantly detected during thiosulfate reduction, suggesting a modified mechanism of sulfite reduction. Proteogenomics suggest a different disproportionation pathway from what has been reported. This work points to an important role of rhodaneses in sulfur processes and these proteins should be considered in searches for sulfur metabolism in broader fields like meta-omics.}, } @article {pmid30307102, year = {2018}, author = {Yang, J and Zeng, ZH and Yang, MJ and Cheng, ZX and Peng, XX and Li, H}, title = {NaCl promotes antibiotic resistance by reducing redox states in Vibrio alginolyticus.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4022-4036}, doi = {10.1111/1462-2920.14443}, pmid = {30307102}, issn = {1462-2920}, support = {2015A030308009//Key project of Natural Science foundation of Guangdong/ ; 31472283//NSFC project/ ; U1701235//NSFC project/ ; 2016YFD0501307//National Key Research and Development Plan/ ; }, abstract = {The development of antibiotic resistance in Vibrio alginolyticus represents a threat to human health and fish farming. Environmental NaCl regulation of bacterial physiology is well documented, but whether the regulation contributes to antibiotic resistance remains unknown. To explore this, we compared minimum inhibitory concentration (MIC) of V. alginolyticus cultured in different media with 0.5%-10% NaCl, and found that the MIC increased as the NaCl concentration increased, especially for aminoglycoside antibiotics. Consistent with this finding, internal NaCl also increased, while intracellular gentamicin level decreased. GC-MS-based metabolomics showed different distributions of pyruvate cycle intermediates among 0.5%, 4% and 10% NaCl. Differential activity of enzymes in the pyruvate cycle and altered expression of Na(+)-NQR led to a reducing redox state, characterized by decreased levels of NADH, proton motive force (PMF) and ATP. Meanwhile, NaCl negatively regulated PMF as a consequence of the reducing redox state. These together are responsible for the decreased intracellular gentamicin level with the increased external level of NaCl. Our study reveals a previously unknown redox state-dependent mechanism regulated by NaCl in V. alginolyticus that impacts antibiotic resistance.}, } @article {pmid30307099, year = {2018}, author = {Imlay, JA}, title = {Where in the world do bacteria experience oxidative stress?.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14445}, pmid = {30307099}, issn = {1462-2920}, support = {GM101012GM49640//National Institute of General Medical Sciences/ ; }, abstract = {Reactive oxygen species - superoxide, hydrogen peroxide and hydroxyl radicals - have long been suspected of constraining bacterial growth in important microbial habitats and indeed of shaping microbial communities. Over recent decades, studies of paradigmatic organisms such as Escherichia coli, Salmonella typhimurium, Bacillus subtilis and Saccharomyces cerevisiae have pinpointed the biomolecules that oxidants can damage and the strategies by which microbes minimize their injuries. What is lacking is a good sense of the circumstances under which oxidative stress actually occurs. In this MiniReview several potential natural sources of oxidative stress are considered: endogenous ROS formation, chemical oxidation of reduced species at oxic-anoxic interfaces, H2 O2 production by lactic acid bacteria, the oxidative burst of phagocytes and the redox-cycling of secreted small molecules. While all of these phenomena can be reproduced and verified in the lab, the actual quantification of stress in natural habitats remains lacking - and, therefore, we have a fundamental hole in our understanding of the role that oxidative stress actually plays in the biosphere.}, } @article {pmid30307098, year = {2018}, author = {Li, D and Pang, L and Yuan, P and Zheng, P and Huai, B and Yao, M and Kang, Z and Liu, J}, title = {A novel citrate synthase isoform contributes infection and stress resistance of the stripe rust fungus.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4037-4050}, doi = {10.1111/1462-2920.14444}, pmid = {30307098}, issn = {1462-2920}, support = {B07049//111 Project of the Ministry of Education of China/ ; 2452018151//Chinese Universities Scientific Fund/ ; 2016YFD0100602//National Key Research and Development Program of China/ ; }, abstract = {The early development of a rust fungus is dependent on the endogenous lipids stored in the urediniospores. After it establishes a parasitic relationship with the host, sugars absorbed from the host cells by haustoria become the primary nutrients. The tricarboxylic acid (TCA) cycle is essential to oxidize these nutrients. However, few studies have addressed the role of citrate synthase (CS), a rate-limiting enzyme of the TCA cycle, during the infection process of rust fungi. In this study, a CS gene from Puccinia striiformis f. sp. tritici (Pst), PsCS1, was cloned and characterized. Transcripts of PsCS1 and the enzyme activity of the CS were increased in the early Pst infection stage. Biochemical features and subcellular localization revealed that PsCS1 encoded a mitochondrial CS. Size exclusion chromatography, yeast two-hybrid and bimolecular fluorescence complementation experiments confirmed that PsCS1 could form a functional homo-octamer. The overexpression of PsCS1 enhanced the resistance of Escherichia coli to salt stress. The knockdown of PsCS1 using a host-induced gene silencing (HIGS) system blocked Pst growth in wheat. These results indicate that PsCS1 is required for nutrient metabolism in Pst and contributes to Pst infection by regulating ATP production and the supply of carbon sources.}, } @article {pmid30306740, year = {2018}, author = {Wackett, LP}, title = {Microbial chemolithotrophy: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {606-607}, doi = {10.1111/1758-2229.12699}, pmid = {30306740}, issn = {1758-2229}, } @article {pmid30306739, year = {2018}, author = {}, title = {PhyMet2 : a database and toolkit for phylogenetic and metabolic analyses of methanogens.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {605}, doi = {10.1111/1758-2229.12676}, pmid = {30306739}, issn = {1758-2229}, } @article {pmid30306205, year = {2018}, author = {Kovacs, NA and Penev, PI and Venapally, A and Petrov, AS and Williams, LD}, title = {Circular Permutation Obscures Universality of a Ribosomal Protein.}, journal = {Journal of molecular evolution}, volume = {86}, number = {8}, pages = {581-592}, pmid = {30306205}, issn = {1432-1432}, support = {NNX16AJ29G//NASA Astrobiology Institute/ ; NNX16AJ28G//National Aeronautics and Space Administration/ ; }, abstract = {Functions, origins, and evolution of the translation system are best understood in the context of unambiguous and phylogenetically based taxonomy and nomenclature. Here, we map ribosomal proteins onto the tree of life and provide a nomenclature for ribosomal proteins that is consistent with phylogenetic relationships. We have increased the accuracy of homology relationships among ribosomal proteins, providing a more informative picture of their lineages. We demonstrate that bL33 (bacteria) and eL42 (archaea/eukarya) are homologs with common ancestry and acute similarities in sequence and structure. Their similarities were previously obscured by circular permutation. The most likely mechanism of permutation between bL33 and eL42 is duplication followed by fusion and deletion of both the first and last β-hairpins. bL33 and eL42 are composed of zinc ribbon protein folds, one of the most common zinc finger fold-groups of, and most frequently observed in translation-related domains. Bacterial-specific ribosomal protein bL33 and archaeal/eukaryotic-specific ribosomal protein eL42 are now both assigned the name of uL33, indicating a universal ribosomal protein. We provide a phylogenetic naming scheme for all ribosomal proteins that is based on phylogenetic relationships to be used as a tool for studying the systemics, evolution, and origins of the ribosome.}, } @article {pmid30305867, year = {2018}, author = {Yun, JH and Sung, H and Kim, HS and Tak, EJ and Kang, W and Lee, JY and Hyun, DW and Kim, PS and Bae, JW}, title = {Complete genome sequence of the halophile bacterium Kushneria konosiri X49T, isolated from salt-fermented Konosirus punctatus.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {19}, pmid = {30305867}, issn = {1944-3277}, abstract = {Kushneria konosiri X49T is a member of the Halomonadaceae family within the order Oceanospirillales and can be isolated from salt-fermented larval gizzard shad. The genome of K. konosiri X49T reported here provides a genetic basis for its halophilic character. Diverse genes were involved in salt-in and -out strategies enabling adaptation of X49T to hypersaline environments. Due to resistance to high salt concentrations, genome research of K. konosiri X49T will contribute to the improvement of environmental and biotechnological usage by enhancing understanding of the osmotic equilibrium in the cytoplasm. Its genome consists of 3,584,631 bp, with an average G + C content of 59.1%, and 3261 coding sequences, 12 rRNAs, 66 tRNAs, and 8 miscRNAs.}, } @article {pmid30305760, year = {2018}, author = {}, title = {Economics Nobel for climate change, Hubble trouble and open-access ups and downs.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {168-169}, doi = {10.1038/d41586-018-06954-5}, pmid = {30305760}, issn = {1476-4687}, } @article {pmid30305759, year = {2018}, author = {Warren, M}, title = {The approach to predictive medicine that is taking genomics research by storm.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {181-183}, doi = {10.1038/d41586-018-06956-3}, pmid = {30305759}, issn = {1476-4687}, } @article {pmid30305758, year = {2018}, author = {Davis, B}, title = {An alternative Japan experience.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {S53-S55}, doi = {10.1038/d41586-018-06961-6}, pmid = {30305758}, issn = {1476-4687}, } @article {pmid30305756, year = {2018}, author = {Scheer, E and Belzig, W}, title = {Unexpected noise from hot electrons.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {200-201}, doi = {10.1038/d41586-018-06932-x}, pmid = {30305756}, issn = {1476-4687}, } @article {pmid30305755, year = {2018}, author = {Meredith, P and Armin, A}, title = {LED technology breaks performance barrier.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {197-198}, doi = {10.1038/d41586-018-06923-y}, pmid = {30305755}, issn = {1476-4687}, mesh = {*Calcium Compounds ; Optics and Photonics ; *Oxides ; Titanium ; }, } @article {pmid30305754, year = {2018}, author = {Cox, N}, title = {UK Biobank shares the promise of big data.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {194-195}, doi = {10.1038/d41586-018-06948-3}, pmid = {30305754}, issn = {1476-4687}, mesh = {*Big Data ; *Biological Specimen Banks ; Genomics ; Health Resources ; United Kingdom ; }, } @article {pmid30305753, year = {2018}, author = {Stekel, D}, title = {First report of antimicrobial resistance pre-dates penicillin.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {192}, doi = {10.1038/d41586-018-06983-0}, pmid = {30305753}, issn = {1476-4687}, } @article {pmid30305752, year = {2018}, author = {Nilsson, JA and Olofsson Bagge, R and Ny, L}, title = {Mouse avatars take off as cancer models.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {192}, doi = {10.1038/d41586-018-06982-1}, pmid = {30305752}, issn = {1476-4687}, } @article {pmid30305751, year = {2018}, author = {Bickmore, W and Cunningham-Burley, S and Frame, M}, title = {Funding mechanisms risk promoting conscious bias.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {192}, doi = {10.1038/d41586-018-06979-w}, pmid = {30305751}, issn = {1476-4687}, } @article {pmid30305750, year = {2018}, author = {Braben, D}, title = {Universities fund off-the-wall research from their own pockets.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {192}, doi = {10.1038/d41586-018-06980-3}, pmid = {30305750}, issn = {1476-4687}, } @article {pmid30305749, year = {2018}, author = {Sonne, C and Hansen, M and Olsen Alstrup, AK}, title = {Protect Denmark's groundwater from pesticides.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {192}, doi = {10.1038/d41586-018-06981-2}, pmid = {30305749}, issn = {1476-4687}, } @article {pmid30305748, year = {2018}, author = {White, EK}, title = {The best supervisor.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {297}, doi = {10.1038/d41586-018-06959-0}, pmid = {30305748}, issn = {1476-4687}, } @article {pmid30305747, year = {2018}, author = {Kwok, R}, title = {Why working as a travel guide or cruise lecturer can be an effective form of science outreach.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {295-297}, doi = {10.1038/d41586-018-06960-7}, pmid = {30305747}, issn = {1476-4687}, } @article {pmid30305746, year = {2018}, author = {Lux, Z}, title = {Mobile hack.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {300}, doi = {10.1038/d41586-018-06962-5}, pmid = {30305746}, issn = {1476-4687}, } @article {pmid30305745, year = {2018}, author = {Lumbroso, OS and Simine, L and Nitzan, A and Segal, D and Tal, O}, title = {Electronic noise due to temperature differences in atomic-scale junctions.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {240-244}, doi = {10.1038/s41586-018-0592-2}, pmid = {30305745}, issn = {1476-4687}, support = {CHE1665291//National Science Foundation/International ; }, abstract = {Since the discovery a century ago1-3 of electronic thermal noise and shot noise, these forms of fundamental noise have had an enormous impact on science and technology research and applications. They can be used to probe quantum effects and thermodynamic quantities4-11, but they are also regarded as undesirable in electronic devices because they obscure the target signal. Electronic thermal noise is generated at equilibrium at finite (non-zero) temperature, whereas electronic shot noise is a non-equilibrium current noise that is generated by partial transmission and reflection (partition) of the incoming electrons8. Until now, shot noise has been stimulated by a voltage, either applied directly8 or activated by radiation12,13. Here we report measurements of a fundamental electronic noise that is generated by temperature differences across nanoscale conductors, which we term 'delta-T noise'. We experimentally demonstrate this noise in atomic and molecular junctions, and analyse it theoretically using the Landauer formalism8,14. Our findings show that delta-T noise is distinct from thermal noise and voltage-activated shot noise8. Like thermal noise, it has a purely thermal origin, but delta-T noise is generated only out of equilibrium. Delta-T noise and standard shot noise have the same partition origin, but are activated by different stimuli. We infer that delta-T noise in combination with thermal noise can be used to detect temperature differences across nanoscale conductors without the need to fabricate sophisticated local probes. Thus it can greatly facilitate the study of heat transport at the nanoscale. In the context of modern electronics, temperature differences are often generated unintentionally across electronic components. Taking into account the contribution of delta-T noise in these cases is likely to be essential for the design of efficient nanoscale electronics at the quantum limit.}, } @article {pmid30305744, year = {2018}, author = {Luyssaert, S and Marie, G and Valade, A and Chen, YY and Njakou Djomo, S and Ryder, J and Otto, J and Naudts, K and Lansø, AS and Ghattas, J and McGrath, MJ}, title = {Trade-offs in using European forests to meet climate objectives.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {259-262}, pmid = {30305744}, issn = {1476-4687}, abstract = {The Paris Agreement promotes forest management as a pathway towards halting climate warming through the reduction of carbon dioxide (CO2) emissions1. However, the climate benefits from carbon sequestration through forest management may be reinforced, counteracted or even offset by concurrent management-induced changes in surface albedo, land-surface roughness, emissions of biogenic volatile organic compounds, transpiration and sensible heat flux2-4. Consequently, forest management could offset CO2 emissions without halting global temperature rise. It therefore remains to be confirmed whether commonly proposed sustainable European forest-management portfolios would comply with the Paris Agreement-that is, whether they can reduce the growth rate of atmospheric CO2, reduce the radiative imbalance at the top of the atmosphere, and neither increase the near-surface air temperature nor decrease precipitation by the end of the twenty-first century. Here we show that the portfolio made up of management systems that locally maximize the carbon sink through carbon sequestration, wood use and product and energy substitution reduces the growth rate of atmospheric CO2, but does not meet any of the other criteria. The portfolios that maximize the carbon sink or forest albedo pass only one-different in each case-criterion. Managing the European forests with the objective of reducing near-surface air temperature, on the other hand, will also reduce the atmospheric CO2 growth rate, thus meeting two of the four criteria. Trade-off are thus unavoidable when using European forests to meet climate objectives. Furthermore, our results demonstrate that if present-day forest cover is sustained, the additional climate benefits achieved through forest management would be modest and local, rather than global. On the basis of these findings, we argue that Europe should not rely on forest management to mitigate climate change. The modest climate effects from changes in forest management imply, however, that if adaptation to future climate were to require large-scale changes in species composition and silvicultural systems over Europe5,6, the forests could be adapted to climate change with neither positive nor negative climate effects.}, } @article {pmid30305743, year = {2018}, author = {Bycroft, C and Freeman, C and Petkova, D and Band, G and Elliott, LT and Sharp, K and Motyer, A and Vukcevic, D and Delaneau, O and O'Connell, J and Cortes, A and Welsh, S and Young, A and Effingham, M and McVean, G and Leslie, S and Allen, N and Donnelly, P and Marchini, J}, title = {The UK Biobank resource with deep phenotyping and genomic data.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {203-209}, doi = {10.1038/s41586-018-0579-z}, pmid = {30305743}, issn = {1476-4687}, support = {090532/Z/09/Z//Wellcome Trust/United Kingdom ; 203141/Z/16/Z//Wellcome Trust/United Kingdom ; 095552/Z/11/Z//Wellcome Trust/United Kingdom ; 10956/Z/13Z//Wellcome Trust/United Kingdom ; 100308/Z/12/Z//Wellcome Trust/United Kingdom ; }, abstract = {The UK Biobank project is a prospective cohort study with deep genetic and phenotypic data collected on approximately 500,000 individuals from across the United Kingdom, aged between 40 and 69 at recruitment. The open resource is unique in its size and scope. A rich variety of phenotypic and health-related information is available on each participant, including biological measurements, lifestyle indicators, biomarkers in blood and urine, and imaging of the body and brain. Follow-up information is provided by linking health and medical records. Genome-wide genotype data have been collected on all participants, providing many opportunities for the discovery of new genetic associations and the genetic bases of complex traits. Here we describe the centralized analysis of the genetic data, including genotype quality, properties of population structure and relatedness of the genetic data, and efficient phasing and genotype imputation that increases the number of testable variants to around 96 million. Classical allelic variation at 11 human leukocyte antigen genes was imputed, resulting in the recovery of signals with known associations between human leukocyte antigen alleles and many diseases.}, } @article {pmid30305742, year = {2018}, author = {Cao, Y and Wang, N and Tian, H and Guo, J and Wei, Y and Chen, H and Miao, Y and Zou, W and Pan, K and He, Y and Cao, H and Ke, Y and Xu, M and Wang, Y and Yang, M and Du, K and Fu, Z and Kong, D and Dai, D and Jin, Y and Li, G and Li, H and Peng, Q and Wang, J and Huang, W}, title = {Perovskite light-emitting diodes based on spontaneously formed submicrometre-scale structures.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {249-253}, doi = {10.1038/s41586-018-0576-2}, pmid = {30305742}, issn = {1476-4687}, abstract = {Light-emitting diodes (LEDs), which convert electricity to light, are widely used in modern society-for example, in lighting, flat-panel displays, medical devices and many other situations. Generally, the efficiency of LEDs is limited by nonradiative recombination (whereby charge carriers recombine without releasing photons) and light trapping1-3. In planar LEDs, such as organic LEDs, around 70 to 80 per cent of the light generated from the emitters is trapped in the device4,5, leaving considerable opportunity for improvements in efficiency. Many methods, including the use of diffraction gratings, low-index grids and buckling patterns, have been used to extract the light trapped in LEDs6-9. However, these methods usually involve complicated fabrication processes and can distort the light-output spectrum and directionality6,7. Here we demonstrate efficient and high-brightness electroluminescence from solution-processed perovskites that spontaneously form submicrometre-scale structures, which can efficiently extract light from the device and retain wavelength- and viewing-angle-independent electroluminescence. These perovskites are formed simply by introducing amino-acid additives into the perovskite precursor solutions. Moreover, the additives can effectively passivate perovskite surface defects and reduce nonradiative recombination. Perovskite LEDs with a peak external quantum efficiency of 20.7 per cent (at a current density of 18 milliamperes per square centimetre) and an energy-conversion efficiency of 12 per cent (at a high current density of 100 milliamperes per square centimetre) can be achieved-values that approach those of the best-performing organic LEDs.}, } @article {pmid30305741, year = {2018}, author = {Lin, K and Xing, J and Quan, LN and de Arquer, FPG and Gong, X and Lu, J and Xie, L and Zhao, W and Zhang, D and Yan, C and Li, W and Liu, X and Lu, Y and Kirman, J and Sargent, EH and Xiong, Q and Wei, Z}, title = {Perovskite light-emitting diodes with external quantum efficiency exceeding 20 per cent.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {245-248}, doi = {10.1038/s41586-018-0575-3}, pmid = {30305741}, issn = {1476-4687}, abstract = {Metal halide perovskite materials are an emerging class of solution-processable semiconductors with considerable potential for use in optoelectronic devices1-3. For example, light-emitting diodes (LEDs) based on these materials could see application in flat-panel displays and solid-state lighting, owing to their potential to be made at low cost via facile solution processing, and could provide tunable colours and narrow emission line widths at high photoluminescence quantum yields4-8. However, the highest reported external quantum efficiencies of green- and red-light-emitting perovskite LEDs are around 14 per cent7,9 and 12 per cent8, respectively-still well behind the performance of organic LEDs10-12 and inorganic quantum dot LEDs13. Here we describe visible-light-emitting perovskite LEDs that surpass the quantum efficiency milestone of 20 per cent. This achievement stems from a new strategy for managing the compositional distribution in the device-an approach that simultaneously provides high luminescence and balanced charge injection. Specifically, we mixed a presynthesized CsPbBr3 perovskite with a MABr additive (where MA is CH3NH3), the differing solubilities of which yield sequential crystallization into a CsPbBr3/MABr quasi-core/shell structure. The MABr shell passivates the nonradiative defects that would otherwise be present in CsPbBr3 crystals, boosting the photoluminescence quantum efficiency, while the MABr capping layer enables balanced charge injection. The resulting 20.3 per cent external quantum efficiency represents a substantial step towards the practical application of perovskite LEDs in lighting and display.}, } @article {pmid30305740, year = {2018}, author = {Elliott, LT and Sharp, K and Alfaro-Almagro, F and Shi, S and Miller, KL and Douaud, G and Marchini, J and Smith, SM}, title = {Genome-wide association studies of brain imaging phenotypes in UK Biobank.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {210-216}, doi = {10.1038/s41586-018-0571-7}, pmid = {30305740}, issn = {1476-4687}, support = {MR/K006673/1//Medical Research Council/United Kingdom ; }, abstract = {The genetic architecture of brain structure and function is largely unknown. To investigate this, we carried out genome-wide association studies of 3,144 functional and structural brain imaging phenotypes from UK Biobank (discovery dataset 8,428 subjects). Here we show that many of these phenotypes are heritable. We identify 148 clusters of associations between single nucleotide polymorphisms and imaging phenotypes that replicate at P < 0.05, when we would expect 21 to replicate by chance. Notable significant, interpretable associations include: iron transport and storage genes, related to magnetic susceptibility of subcortical brain tissue; extracellular matrix and epidermal growth factor genes, associated with white matter micro-structure and lesions; genes that regulate mid-line axon development, associated with organization of the pontine crossing tract; and overall 17 genes involved in development, pathway signalling and plasticity. Our results provide insights into the genetic architecture of the brain that are relevant to neurological and psychiatric disorders, brain development and ageing.}, } @article {pmid30305738, year = {2018}, author = {Song, M and Sandoval, TA and Chae, CS and Chopra, S and Tan, C and Rutkowski, MR and Raundhal, M and Chaurio, RA and Payne, KK and Konrad, C and Bettigole, SE and Shin, HR and Crowley, MJP and Cerliani, JP and Kossenkov, AV and Motorykin, I and Zhang, S and Manfredi, G and Zamarin, D and Holcomb, K and Rodriguez, PC and Rabinovich, GA and Conejo-Garcia, JR and Glimcher, LH and Cubillos-Ruiz, JR}, title = {IRE1α-XBP1 controls T cell function in ovarian cancer by regulating mitochondrial activity.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {423-428}, pmid = {30305738}, issn = {1476-4687}, support = {R01 CA112663/CA/NCI NIH HHS/United States ; R01 CA184185/CA/NCI NIH HHS/United States ; 1S10 OD017992-01/OD/NIH HHS/United States ; }, abstract = {Tumours evade immune control by creating hostile microenvironments that perturb T cell metabolism and effector function1-4. However, it remains unclear how intra-tumoral T cells integrate and interpret metabolic stress signals. Here we report that ovarian cancer-an aggressive malignancy that is refractory to standard treatments and current immunotherapies5-8-induces endoplasmic reticulum stress and activates the IRE1α-XBP1 arm of the unfolded protein response9,10 in T cells to control their mitochondrial respiration and anti-tumour function. In T cells isolated from specimens collected from patients with ovarian cancer, upregulation of XBP1 was associated with decreased infiltration of T cells into tumours and with reduced IFNG mRNA expression. Malignant ascites fluid obtained from patients with ovarian cancer inhibited glucose uptake and caused N-linked protein glycosylation defects in T cells, which triggered IRE1α-XBP1 activation that suppressed mitochondrial activity and IFNγ production. Mechanistically, induction of XBP1 regulated the abundance of glutamine carriers and thus limited the influx of glutamine that is necessary to sustain mitochondrial respiration in T cells under glucose-deprived conditions. Restoring N-linked protein glycosylation, abrogating IRE1α-XBP1 activation or enforcing expression of glutamine transporters enhanced mitochondrial respiration in human T cells exposed to ovarian cancer ascites. XBP1-deficient T cells in the metastatic ovarian cancer milieu exhibited global transcriptional reprogramming and improved effector capacity. Accordingly, mice that bear ovarian cancer and lack XBP1 selectively in T cells demonstrate superior anti-tumour immunity, delayed malignant progression and increased overall survival. Controlling endoplasmic reticulum stress or targeting IRE1α-XBP1 signalling may help to restore the metabolic fitness and anti-tumour capacity of T cells in cancer hosts.}, } @article {pmid30305737, year = {2018}, author = {Rajakumar, R and Koch, S and Couture, M and Favé, MJ and Lillico-Ouachour, A and Chen, T and De Blasis, G and Rajakumar, A and Ouellette, D and Abouheif, E}, title = {Social regulation of a rudimentary organ generates complex worker-caste systems in ants.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {574-577}, doi = {10.1038/s41586-018-0613-1}, pmid = {30305737}, issn = {1476-4687}, abstract = {The origin of complex worker-caste systems in ants perplexed Darwin1 and has remained an enduring problem for evolutionary and developmental biology2-6. Ants originated approximately 150 million years ago, and produce colonies with winged queen and male castes as well as a wingless worker caste7. In the hyperdiverse genus Pheidole, the wingless worker caste has evolved into two morphologically distinct subcastes-small-headed minor workers and large-headed soldiers8. The wings of queens and males develop from populations of cells in larvae that are called wing imaginal discs7. Although minor workers and soldiers are wingless, vestiges or rudiments of wing imaginal discs appear transiently during soldier development7,9-11. Such rudimentary traits are phylogenetically widespread and are primarily used as evidence of common descent, yet their functional importance remains equivocal1,12-14. Here we show that the growth of rudimentary wing discs is necessary for regulating allometry-disproportionate scaling-between head and body size to generate large-headed soldiers in the genus Pheidole. We also show that Pheidole colonies have evolved the capacity to socially regulate the growth of rudimentary wing discs to control worker subcaste determination, which allows these colonies to maintain the ratio of minor workers to soldiers. Finally, we provide comparative and experimental evidence that suggests that rudimentary wing discs have facilitated the parallel evolution of complex worker-caste systems across the ants. More generally, rudimentary organs may unexpectedly acquire novel regulatory functions during development to facilitate adaptive evolution.}, } @article {pmid30305736, year = {2018}, author = {Piewngam, P and Zheng, Y and Nguyen, TH and Dickey, SW and Joo, HS and Villaruz, AE and Glose, KA and Fisher, EL and Hunt, RL and Li, B and Chiou, J and Pharkjaksu, S and Khongthong, S and Cheung, GYC and Kiratisin, P and Otto, M}, title = {Pathogen elimination by probiotic Bacillus via signalling interference.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {532-537}, pmid = {30305736}, issn = {1476-4687}, support = {Z01 AI000904-07//NULL/International ; ZIA AI000904/AI/NIAID NIH HHS/United States ; }, abstract = {Probiotic nutrition is frequently claimed to improve human health. In particular, live probiotic bacteria obtained with food are thought to reduce intestinal colonization by pathogens, and thus to reduce susceptibility to infection. However, the mechanisms that underlie these effects remain poorly understood. Here we report that the consumption of probiotic Bacillus bacteria comprehensively abolished colonization by the dangerous pathogen Staphylococcus aureus in a rural Thai population. We show that a widespread class of Bacillus lipopeptides, the fengycins, eliminates S. aureus by inhibiting S. aureus quorum sensing-a process through which bacteria respond to their population density by altering gene regulation. Our study presents a detailed molecular mechanism that underlines the importance of probiotic nutrition in reducing infectious disease. We also provide evidence that supports the biological significance of probiotic bacterial interference in humans, and show that such interference can be achieved by blocking a pathogen's signalling system. Furthermore, our findings suggest a probiotic-based method for S. aureus decolonization and new ways to fight S. aureus infections.}, } @article {pmid30305735, year = {2018}, author = {Satkunendrarajah, K and Karadimas, SK and Laliberte, AM and Montandon, G and Fehlings, MG}, title = {Cervical excitatory neurons sustain breathing after spinal cord injury.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {419-422}, doi = {10.1038/s41586-018-0595-z}, pmid = {30305735}, issn = {1476-4687}, abstract = {Dysfunctional breathing is the main cause of morbidity and mortality after traumatic injury of the cervical spinal cord1,2 and often necessitates assisted ventilation, thus stressing the need to develop strategies to restore breathing. Cervical interneurons that form synapses on phrenic motor neurons, which control the main inspiratory muscle, can modulate phrenic motor output and diaphragmatic function3-5. Here, using a combination of pharmacogenetics and respiratory physiology assays in different models of spinal cord injury, we show that mid-cervical excitatory interneurons are essential for the maintenance of breathing in mice with non-traumatic cervical spinal cord injury, and are also crucial for promoting respiratory recovery after traumatic spinal cord injury. Although these interneurons are not necessary for breathing under normal conditions, their stimulation in non-injured animals enhances inspiratory amplitude. Immediately after spinal cord injury, pharmacogenetic stimulation of cervical excitatory interneurons restores respiratory motor function. Overall, our results demonstrate a strategy to restore breathing after central nervous system trauma by targeting a neuronal subpopulation.}, } @article {pmid30305734, year = {2018}, author = {Chang, AN and Liang, Z and Dai, HQ and Chapdelaine-Williams, AM and Andrews, N and Bronson, RT and Schwer, B and Alt, FW}, title = {Neural blastocyst complementation enables mouse forebrain organogenesis.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {126-130}, doi = {10.1038/s41586-018-0586-0}, pmid = {30305734}, issn = {1476-4687}, support = {1U54HD090255/HD/NICHD NIH HHS/United States ; K01 AG043630/AG/NIA NIH HHS/United States ; }, abstract = {Genetically modified mice are commonly generated by the microinjection of pluripotent embryonic stem (ES) cells into wild-type host blastocysts1, producing chimeric progeny that require breeding for germline transmission and homozygosity of modified alleles. As an alternative approach and to facilitate studies of the immune system, we previously developed RAG2-deficient blastocyst complementation2. Because RAG2-deficient mice cannot undergo V(D)J recombination, they do not develop B or T lineage cells beyond the progenitor stage2: injecting RAG2-sufficient donor ES cells into RAG2-deficient blastocysts generates somatic chimaeras in which all mature lymphocytes derive from donor ES cells. This enables analysis, in mature lymphocytes, of the functions of genes that are required more generally for mouse development3. Blastocyst complementation has been extended to pancreas organogenesis4, and used to generate several other tissues or organs5-10, but an equivalent approach for brain organogenesis has not yet been achieved. Here we describe neural blastocyst complementation (NBC), which can be used to study the development and function of specific forebrain regions. NBC involves targeted ablation, mediated by diphtheria toxin subunit A, of host-derived dorsal telencephalic progenitors during development. This ablation creates a vacant forebrain niche in host embryos that results in agenesis of the cerebral cortex and hippocampus. Injection of donor ES cells into blastocysts with forebrain-specific targeting of diphtheria toxin subunit A enables donor-derived dorsal telencephalic progenitors to populate the vacant niche in the host embryos, giving rise to neocortices and hippocampi that are morphologically and neurologically normal with respect to learning and memory formation. Moreover, doublecortin-deficient ES cells-generated via a CRISPR-Cas9 approach-produced NBC chimaeras that faithfully recapitulated the phenotype of conventional, germline doublecortin-deficient mice. We conclude that NBC is a rapid and efficient approach to generate complex mouse models for studying forebrain functions; this approach could more broadly facilitate organogenesis based on blastocyst complementation.}, } @article {pmid30305733, year = {2018}, author = {Wiwatpanit, T and Lorenzen, SM and Cantú, JA and Foo, CZ and Hogan, AK and Márquez, F and Clancy, JC and Schipma, MJ and Cheatham, MA and Duggan, A and García-Añoveros, J}, title = {Trans-differentiation of outer hair cells into inner hair cells in the absence of INSM1.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {691-695}, pmid = {30305733}, issn = {1476-4687}, support = {R01 DC015903/DC/NIDCD NIH HHS/United States ; R25 GM079300/GM/NIGMS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R01 DC000089/DC/NIDCD NIH HHS/United States ; F31 DC012483/DC/NIDCD NIH HHS/United States ; }, abstract = {The mammalian cochlea contains two types of mechanosensory hair cell that have different and critical functions in hearing. Inner hair cells (IHCs), which have an elaborate presynaptic apparatus, signal to cochlear neurons and communicate sound information to the brain. Outer hair cells (OHCs) mechanically amplify sound-induced vibrations, providing enhanced sensitivity to sound and sharp tuning. Cochlear hair cells are solely generated during development, and hair cell death-most often of OHCs-is the most common cause of deafness. OHCs and IHCs, together with supporting cells, originate in embryos from the prosensory region of the otocyst, but how hair cells differentiate into two different types is unknown1-3. Here we show that Insm1, which encodes a zinc finger protein that is transiently expressed in nascent OHCs, consolidates their fate by preventing trans-differentiation into IHCs. In the absence of INSM1, many hair cells that are born as OHCs switch fates to become mature IHCs. To identify the genetic mechanisms by which Insm1 operates, we compared the transcriptomes of immature IHCs and OHCs, and of OHCs with and without INSM1. In OHCs that lack INSM1, a set of genes is upregulated, most of which are normally preferentially expressed by IHCs. The homeotic cell transformation of OHCs without INSM1 into IHCs reveals a mechanism by which these neighbouring mechanosensory cells begin to differ: INSM1 represses a core set of early IHC-enriched genes in embryonic OHCs and makes them unresponsive to an IHC-inducing gradient, so that they proceed to mature as OHCs. Without INSM1, some of the OHCs in which these few IHC-enriched transcripts are upregulated trans-differentiate into IHCs, identifying candidate genes for IHC-specific differentiation.}, } @article {pmid30305732, year = {2018}, author = {Shannon, RM and Macquart, JP and Bannister, KW and Ekers, RD and James, CW and Osłowski, S and Qiu, H and Sammons, M and Hotan, AW and Voronkov, MA and Beresford, RJ and Brothers, M and Brown, AJ and Bunton, JD and Chippendale, AP and Haskins, C and Leach, M and Marquarding, M and McConnell, D and Pilawa, MA and Sadler, EM and Troup, ER and Tuthill, J and Whiting, MT and Allison, JR and Anderson, CS and Bell, ME and Collier, JD and Gürkan, G and Heald, G and Riseley, CJ}, title = {The dispersion-brightness relation for fast radio bursts from a wide-field survey.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {386-390}, doi = {10.1038/s41586-018-0588-y}, pmid = {30305732}, issn = {1476-4687}, abstract = {Despite considerable efforts over the past decade, only 34 fast radio bursts-intense bursts of radio emission from beyond our Galaxy-have been reported1,2. Attempts to understand the population as a whole have been hindered by the highly heterogeneous nature of the searches, which have been conducted with telescopes of different sensitivities, at a range of radio frequencies, and in environments corrupted by different levels of radio-frequency interference from human activity. Searches have been further complicated by uncertain burst positions and brightnesses-a consequence of the transient nature of the sources and the poor angular resolution of the detecting instruments. The discovery of repeating bursts from one source3, and its subsequent localization4 to a dwarf galaxy at a distance of 3.7 billion light years, confirmed that the population of fast radio bursts is located at cosmological distances. However, the nature of the emission remains elusive. Here we report a well controlled, wide-field radio survey for these bursts. We found 20, none of which repeated during follow-up observations between 185-1,097 hours after the initial detections. The sample includes both the nearest and the most energetic bursts detected so far. The survey demonstrates that there is a relationship between burst dispersion and brightness and that the high-fluence bursts are the nearby analogues of the more distant events found in higher-sensitivity, narrower-field surveys5.}, } @article {pmid30305731, year = {2018}, author = {Springmann, M and Clark, M and Mason-D'Croz, D and Wiebe, K and Bodirsky, BL and Lassaletta, L and de Vries, W and Vermeulen, SJ and Herrero, M and Carlson, KM and Jonell, M and Troell, M and DeClerck, F and Gordon, LJ and Zurayk, R and Scarborough, P and Rayner, M and Loken, B and Fanzo, J and Godfray, HCJ and Tilman, D and Rockström, J and Willett, W}, title = {Options for keeping the food system within environmental limits.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {519-525}, doi = {10.1038/s41586-018-0594-0}, pmid = {30305731}, issn = {1476-4687}, abstract = {The food system is a major driver of climate change, changes in land use, depletion of freshwater resources, and pollution of aquatic and terrestrial ecosystems through excessive nitrogen and phosphorus inputs. Here we show that between 2010 and 2050, as a result of expected changes in population and income levels, the environmental effects of the food system could increase by 50-90% in the absence of technological changes and dedicated mitigation measures, reaching levels that are beyond the planetary boundaries that define a safe operating space for humanity. We analyse several options for reducing the environmental effects of the food system, including dietary changes towards healthier, more plant-based diets, improvements in technologies and management, and reductions in food loss and waste. We find that no single measure is enough to keep these effects within all planetary boundaries simultaneously, and that a synergistic combination of measures will be needed to sufficiently mitigate the projected increase in environmental pressures.}, } @article {pmid30305704, year = {2018}, author = {Geoghegan, JL and Holmes, EC}, title = {The phylogenomics of evolving virus virulence.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {756-769}, doi = {10.1038/s41576-018-0055-5}, pmid = {30305704}, issn = {1471-0064}, abstract = {How virulence evolves after a virus jumps to a new host species is central to disease emergence. Our current understanding of virulence evolution is based on insights drawn from two perspectives that have developed largely independently: long-standing evolutionary theory based on limited real data examples that often lack a genomic basis, and experimental studies of virulence-determining mutations using cell culture or animal models. A more comprehensive understanding of virulence mutations and their evolution can be achieved by bridging the gap between these two research pathways through the phylogenomic analysis of virus genome sequence data as a guide to experimental study.}, } @article {pmid30305426, year = {2018}, author = {Wong, MY and Chen, K and Antonopoulos, A and Kasper, BT and Dewal, MB and Taylor, RJ and Whittaker, CA and Hein, PP and Dell, A and Genereux, JC and Haslam, SM and Mahal, LK and Shoulders, MD}, title = {XBP1s activation can globally remodel N-glycan structure distribution patterns.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10089-E10098}, pmid = {30305426}, issn = {1091-6490}, support = {F32 HL099245/HL/NHLBI NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; U01 AI111598/AI/NIAID NIH HHS/United States ; BB/K016164/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Line ; Cell Line, Tumor ; HEK293 Cells ; HeLa Cells ; Humans ; Mannose/metabolism ; Polysaccharides/*metabolism ; Proteome/metabolism ; Signal Transduction/physiology ; Transcription, Genetic/physiology ; Unfolded Protein Response/physiology ; X-Box Binding Protein 1/*metabolism ; }, abstract = {Classically, the unfolded protein response (UPR) safeguards secretory pathway proteostasis. The most ancient arm of the UPR, the IRE1-activated spliced X-box binding protein 1 (XBP1s)-mediated response, has roles in secretory pathway maturation beyond resolving proteostatic stress. Understanding the consequences of XBP1s activation for cellular processes is critical for elucidating mechanistic connections between XBP1s and development, immunity, and disease. Here, we show that a key functional output of XBP1s activation is a cell type-dependent shift in the distribution of N-glycan structures on endogenous membrane and secreted proteomes. For example, XBP1s activity decreased levels of sialylation and bisecting GlcNAc in the HEK293 membrane proteome and secretome, while substantially increasing the population of oligomannose N-glycans only in the secretome. In HeLa cell membranes, stress-independent XBP1s activation increased the population of high-mannose and tetraantennary N-glycans, and also enhanced core fucosylation. mRNA profiling experiments suggest that XBP1s-mediated remodeling of the N-glycome is, at least in part, a consequence of coordinated transcriptional resculpting of N-glycan maturation pathways by XBP1s. The discovery of XBP1s-induced N-glycan structural remodeling on a glycome-wide scale suggests that XBP1s can act as a master regulator of N-glycan maturation. Moreover, because the sugars on cell-surface proteins or on proteins secreted from an XBP1s-activated cell can be molecularly distinct from those of an unactivated cell, these findings reveal a potential new mechanism for translating intracellular stress signaling into altered interactions with the extracellular environment.}, } @article {pmid30305425, year = {2018}, author = {Knecht, KM and Buzovetsky, O and Schneider, C and Thomas, D and Srikanth, V and Kaderali, L and Tofoleanu, F and Reiss, K and Ferreirós, N and Geisslinger, G and Batista, VS and Ji, X and Cinatl, J and Keppler, OT and Xiong, Y}, title = {The structural basis for cancer drug interactions with the catalytic and allosteric sites of SAMHD1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10022-E10031}, pmid = {30305425}, issn = {1091-6490}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; T32 GM007223/GM/NIGMS NIH HHS/United States ; R21 AI136737/AI/NIAID NIH HHS/United States ; T32 GM008283/GM/NIGMS NIH HHS/United States ; K99 AI120845/AI/NIAID NIH HHS/United States ; }, mesh = {Allosteric Site/*drug effects ; Antineoplastic Agents/pharmacology ; Catalytic Domain/*drug effects ; Cell Line, Tumor ; Crystallography, X-Ray/methods ; Drug Interactions/*physiology ; HL-60 Cells ; Humans ; Leukemia, Myeloid, Acute/drug therapy/*metabolism ; Nucleotides/pharmacology ; SAM Domain and HD Domain-Containing Protein 1/*metabolism ; Substrate Specificity ; }, abstract = {SAMHD1 is a deoxynucleoside triphosphate triphosphohydrolase (dNTPase) that depletes cellular dNTPs in noncycling cells to promote genome stability and to inhibit retroviral and herpes viral replication. In addition to being substrates, cellular nucleotides also allosterically regulate SAMHD1 activity. Recently, it was shown that high expression levels of SAMHD1 are also correlated with significantly worse patient responses to nucleotide analog drugs important for treating a variety of cancers, including acute myeloid leukemia (AML). In this study, we used biochemical, structural, and cellular methods to examine the interactions of various cancer drugs with SAMHD1. We found that both the catalytic and the allosteric sites of SAMHD1 are sensitive to sugar modifications of the nucleotide analogs, with the allosteric site being significantly more restrictive. We crystallized cladribine-TP, clofarabine-TP, fludarabine-TP, vidarabine-TP, cytarabine-TP, and gemcitabine-TP in the catalytic pocket of SAMHD1. We found that all of these drugs are substrates of SAMHD1 and that the efficacy of most of these drugs is affected by SAMHD1 activity. Of the nucleotide analogs tested, only cladribine-TP with a deoxyribose sugar efficiently induced the catalytically active SAMHD1 tetramer. Together, these results establish a detailed framework for understanding the substrate specificity and allosteric activation of SAMHD1 with regard to nucleotide analogs, which can be used to improve current cancer and antiviral therapies.}, } @article {pmid30305424, year = {2018}, author = {Sun, XX and Chen, Y and Su, Y and Wang, X and Chauhan, KM and Liang, J and Daniel, CJ and Sears, RC and Dai, MS}, title = {SUMO protease SENP1 deSUMOylates and stabilizes c-Myc.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10983-10988}, pmid = {30305424}, issn = {1091-6490}, support = {R01 CA100855/CA/NCI NIH HHS/United States ; R01 CA160474/CA/NCI NIH HHS/United States ; R01 CA186241/CA/NCI NIH HHS/United States ; }, mesh = {Breast Neoplasms/metabolism ; Cell Cycle Checkpoints/physiology ; Cell Line ; Cell Line, Tumor ; Cell Proliferation/physiology ; Cysteine Endopeptidases/*metabolism ; Female ; HCT116 Cells ; HEK293 Cells ; HeLa Cells ; Humans ; MCF-7 Cells ; Proteasome Endopeptidase Complex/metabolism ; Protein Processing, Post-Translational/physiology ; Proto-Oncogene Proteins c-myc/*metabolism ; SUMO-1 Protein/*metabolism ; Sumoylation/physiology ; Ubiquitination/physiology ; }, abstract = {Posttranslational modifications play a crucial role in the proper control of c-Myc protein stability and activity. c-Myc can be modified by small ubiquitin-like modifier (SUMO). However, how SUMOylation regulates c-Myc stability and activity remains to be elucidated. The deSUMOylation enzyme, SENP1, has recently been shown to have a prooncogenic role in cancer; however, mechanistic understanding of this is limited. Here we show that SENP1 is a c-Myc deSUMOylating enzyme. SENP1 interacts with and deSUMOylates c-Myc in cells and in vitro. Overexpression of wild-type SENP1, but not its catalytically inactive C603S mutant, markedly stabilizes c-Myc and increases its levels and activity. Knockdown of SENP1 reduces c-Myc levels, induces cell cycle arrest, and drastically suppresses cell proliferation. We further show that c-Myc can be comodified by both ubiquitination and SUMOylation. SENP1-mediated deSUMOylation reduces c-Myc polyubiquitination, suggesting that SUMOylation promotes c-Myc degradation through the proteasome system. Interestingly, SENP1-mediated deSUMOylation promotes the accumulation of monoubiquitinated c-Myc and its phosphorylation at serine 62 and threonine 58. SENP1 is frequently overexpressed, correlating with the high expression of c-Myc, in breast cancer tissues. Together, these results reveal that SENP1 is a crucial c-Myc deSUMOylating enzyme that positively regulates c-Myc's stability and activity.}, } @article {pmid30305186, year = {2018}, author = {Hailu, T and Nigus, K and Gidey, G and Hailu, B and Moges, Y}, title = {Assessment of partograph utilization and associated factors among obstetric care givers at public health institutions in central zone, Tigray, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {710}, pmid = {30305186}, issn = {1756-0500}, mesh = {Adult ; Caregivers/education/*psychology ; Cross-Sectional Studies ; Ethiopia ; Female ; Fetal Monitoring/*statistics & numerical data ; *Health Knowledge, Attitudes, Practice ; Humans ; Labor, Obstetric/*physiology ; Male ; Parturition/physiology ; Placental Function Tests/*statistics & numerical data ; Pregnancy ; Public Health/instrumentation ; Surveys and Questionnaires ; Uterine Monitoring/*statistics & numerical data ; }, abstract = {OBJECTIVES: Partograph is one of the best effective obstetric tools used to monitoring labor and prevent prolonged or obstructed labor which accounts for about 22% of maternal deaths in Ethiopia. This study was aimed to assess partograph utilization and associated factors among obstetric care givers. Facility based cross sectional study was used in the randomly selected health facilities. Total 220 obstetric care givers were selected using simple random sampling technique. Data were entered and analyzed using SPSS version 22.0. Bivariate and multivariate logistic regression analysis was used to identify the associations of each explanatory variable with the outcome variable. Finally, odds ratio with its 95% confidence interval and p-value of 0.05 was used to identify significant variables.

RESULT: Out of 198 obstetric care providers, 73.3% used partograph to monitor progress of labor. Those who were diploma holders (AOR = 3.8, CI = 2.2-6.2), receiving basic emergency obstetrics and new born care training (AOR = 5.6, CI 1.1-28.5), age between 20 and 29 years-old (AOR = 0.1, CI = 0.01-0.50), and male health care providers (AOR = 0.37, CI = 0.44-0.95) were factors significantly associated with partograph utilization. Partograph utilization in this study was below the WHO recommendation. Especial emphasizes and interventions should be given to increase partograph utilization.}, } @article {pmid30305181, year = {2018}, author = {Khashei, R and Malekzadegan, Y and Sedigh Ebrahim-Saraie, H and Razavi, Z}, title = {Phenotypic and genotypic characterization of macrolide, lincosamide and streptogramin B resistance among clinical isolates of staphylococci in southwest of Iran.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {711}, pmid = {30305181}, issn = {1756-0500}, support = {93-8690//Shiraz University of Medical Sciences/ ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*pharmacology ; Child ; Child, Preschool ; Cross-Sectional Studies ; Drug Resistance, Multiple, Bacterial/genetics ; Female ; *Genes, Bacterial ; Genotype ; Humans ; Infant ; Infant, Newborn ; Iran/epidemiology ; Lincosamides/*pharmacology ; Macrolides/*pharmacology ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Phenotype ; Staphylococcal Infections/drug therapy/epidemiology/microbiology ; Staphylococcus/classification/*drug effects/genetics/isolation & purification ; Staphylococcus aureus/classification/*drug effects/genetics/isolation & purification ; Streptogramin B/*pharmacology ; Tertiary Care Centers ; }, abstract = {OBJECTIVE: The present study aimed to determine the phenotypic and genotypic profile of macrolide, lincosamide and streptogramin B (MLSB) resistance in clinical isolates of staphylococci.

RESULTS: This cross-sectional study was conducted on 164 non-duplicated staphylococci isolates collected during August 2015 to February 2016 from two tertiary care hospitals in Shiraz, southwest of Iran. Of the 164 isolates, 86 erythromycin-resistant isolates consist of 35 Staphylococcus aureus and 51 coagulase negative staphylococci (CoNS) were included in the study. Of the 35 S. aureus, the prevalence of cMLS (constitutive), iMLS (inducible), and MS phenotypes were found 82.9%, 8.6% and 8.6%, respectively. Among 51 CoNS, the frequencies of cMLS, iMLS, and MS phenotypes were detected 66.7%, 11.8% and 21.6%, respectively. Among S. aureus isolates, the predominant genes were ermC in 82.9% isolates, followed by ermA in 57.1% and msrA in 28.6% of isolates. Among CoNS isolates, the most frequent genes were diagnosed ermC in 70.6% isolates followed by msrA in 68.6% and ermA in 11.8% of isolates. In conclusion, regarding the presence of MLSB resistance in our region, diagnosis of this resistance type on a routine basis in staphylococcal clinical isolates is of particular importance.}, } @article {pmid30305180, year = {2018}, author = {Zewdie, T and Azale, T and Shimeka, A and Lakew, AM}, title = {Self-medication during pregnancy and associated factors among pregnant women in Goba town, southeast Ethiopia: a community based cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {713}, pmid = {30305180}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Educational Status ; Ethiopia ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Patient Acceptance of Health Care/psychology/*statistics & numerical data ; Pregnancy ; Pregnant Women/*psychology ; Self Medication/psychology/*statistics & numerical data ; }, abstract = {OBJECTIVE: The use of self-medications during pregnancy results in serious structural as well as functional adverse effects on mothers and unborn children. But little is known about the practice of self-medication used during pregnancy in Ethiopia. Therefore, this research aimed to assess the prevalence of self-medication practice and associated factors during pregnancy among pregnant women in Goba town, southeast Ethiopia.

RESULTS: The prevalence of self-medication was 15.5% (95% CI 0.116, 0.195) in Goba town. Women who had health problems during pregnancy (AOR = 6.1, 95% CI 2.67, 13.9), women unable to read and write (AOR = 8.87, 95% CI 1.84, 41.95), those who can read and write (AOR = 5.26, 95% CI 1.34, 20.66) and had primary education (AOR = 3.57, 95% CI 1.42, 9.02) were more likely to use self-medication, while women who visited ANC for pregnancy (AOR = 0.028, 95% CI 0.09, 0.87) were less likely to indulge on such practices. In conclusion, the prevalence of self-medication noted in this work is medium compared to the react of other studies. Health institutions have to give health education to all pregnant women attending ANC services regardless of gestational age and types of health problem.}, } @article {pmid30305168, year = {2018}, author = {Letendre, C and Young, LJ and Old, JM}, title = {Limitations in the isolation and stimulation of splenic mononuclear cells in a dasyurid marsupial, Phascogale calura.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {712}, pmid = {30305168}, issn = {1756-0500}, mesh = {Animals ; Australia ; Cell Separation/*methods ; Female ; Leukocytes, Mononuclear/cytology/*drug effects/immunology ; Male ; Marsupialia/*immunology ; Phytohemagglutinins/*pharmacology ; Primary Cell Culture ; Spleen/cytology/drug effects/immunology ; }, abstract = {OBJECTIVE: Marsupials suffer from an increasing number of stressors in this changing world. Functional studies are thus needed to broaden our understanding of the marsupial immune system. The red-tailed phascogale (Phascogale calura) is a small Australian marsupial previously used in descriptive immunological studies. Here, we aimed to develop functional assays by isolating and stimulating blood and spleen mononuclear cells in vitro.

RESULTS: While peripheral blood mononuclear cell (PBMC) were relatively easy to isolate, only 105 mononuclear cells (> 90% purity and > 75% viability) could be recovered from the spleen, independently of the sex and age of the animal or the centrifugation time and speed tested. The pores of the mesh sieve used for tissue homogenization might have been too big to yield a single cell suspension. Nevertheless, in spite of the overall low number of cells recovered, PBMC and splenic mononuclear cells were successfully activated in preliminary trials with phytohemaglutinin. This activation state was evidenced by a change in shape and the presence of small cell aggregations in the mitogen-stimulated cultures. A non-radioactive colorimetric assay was also performed to confirm cell proliferation in these wells. This work highlights the importance of developing and reporting detailed methodological protocols in non-traditional research species.}, } @article {pmid30305166, year = {2018}, author = {Guyomar, C and Legeai, F and Jousselin, E and Mougel, C and Lemaitre, C and Simon, JC}, title = {Multi-scale characterization of symbiont diversity in the pea aphid complex through metagenomic approaches.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {181}, pmid = {30305166}, issn = {2049-2618}, abstract = {BACKGROUND: Most metazoans are involved in durable relationships with microbes which can take several forms, from mutualism to parasitism. The advances of NGS technologies and bioinformatics tools have opened opportunities to shed light on the diversity of microbial communities and to give some insights into the functions they perform in a broad array of hosts. The pea aphid is a model system for the study of insect-bacteria symbiosis. It is organized in a complex of biotypes, each adapted to specific host plants. It harbors both an obligatory symbiont supplying key nutrients and several facultative symbionts bringing additional functions to the host, such as protection against biotic and abiotic stresses. However, little is known on how the symbiont genomic diversity is structured at different scales: across host biotypes, among individuals of the same biotype, or within individual aphids, which limits our understanding on how these multi-partner symbioses evolve and interact.

RESULTS: We present a framework well adapted to the study of genomic diversity and evolutionary dynamics of the pea aphid holobiont from metagenomic read sets, based on mapping to reference genomes and whole genome variant calling. Our results revealed that the pea aphid microbiota is dominated by a few heritable bacterial symbionts reported in earlier works, with no discovery of new microbial associates. However, we detected a large and heterogeneous genotypic diversity associated with the different symbionts of the pea aphid. Partitioning analysis showed that this fine resolution diversity is distributed across the three considered scales. Phylogenetic analyses highlighted frequent horizontal transfers of facultative symbionts between host lineages, indicative of flexible associations between the pea aphid and its microbiota. However, the evolutionary dynamics of symbiotic associations strongly varied depending on the symbiont, reflecting different histories and possible constraints. In addition, at the intra-host scale, we showed that different symbiont strains may coexist inside the same aphid host.

CONCLUSIONS: We present a methodological framework for the detailed analysis of NGS data from microbial communities of moderate complexity and gave major insights into the extent of diversity in pea aphid-symbiont associations and the range of evolutionary trajectories they could take.}, } @article {pmid30305162, year = {2018}, author = {Quade, FSC and Preitz, B and Prpic, NM}, title = {A perforated anodised aluminium slide for improved specimen clearing and imaging for confocal laser scanning microscopy.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {716}, pmid = {30305162}, issn = {1756-0500}, support = {PR1109/6-1//Deutsche Forschungsgemeinschaft/ ; PR1109/6-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Aluminum/chemistry ; Animals ; Humans ; Male ; Microscopy, Confocal/*instrumentation ; Specimen Handling/*instrumentation/methods ; Spiders/anatomy & histology/*ultrastructure ; }, abstract = {OBJECTIVE: The bleaching, clearing and handling of tiny specimens with soft tissue and cuticular components for confocal laser scanning microscopy is difficult, because after cuticle bleaching and tissue clearing the specimens are virtually invisible. We have adjusted the design of the specimen container described by Smolla et al. (Arthropod Struct Dev 43:175-81, 2014) to handle tiny specimens.

RESULTS: We describe a perforated and anodised aluminium slide that was designed to hold the distal tips of the pedipalp appendages of the spider Parasteatoda tepidariorum during clearing, and that can then be used directly for confocal laser scanning microscopy. We believe that this slide design will be helpful for others who want to visualise specimens between 500 and 800 µm with confocal laser scanning microscopy.}, } @article {pmid30305159, year = {2018}, author = {Mochache, V and Lakhani, A and El-Busaidy, H and Temmerman, M and Gichangi, P}, title = {Correlates of facility-based delivery among women of reproductive age from the Digo community residing in Kwale, Kenya.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {715}, pmid = {30305159}, issn = {1756-0500}, support = {Grant Agreement #265448//European Commission Seventh Framework Programme/ ; Contract # DCI-NSAPVD/2011/276-298//Delegation of the European Commission in Kenya/ ; }, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Delivery, Obstetric/psychology/*statistics & numerical data ; *Educational Status ; Family Characteristics ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Kenya ; Middle Aged ; Parturition/psychology ; Pregnancy ; Prenatal Care/*statistics & numerical data ; Rural Population ; }, abstract = {OBJECTIVE: This study sought to describe factors associated with facility-based delivery among women of reproductive age in Kwale County, Kenya.

RESULTS: Between March and December 2015, 745 women from 15 villages were interviewed through a cross-sectional household survey. Respondents were selected using stratified, systematic sampling and completed a sexual and reproductive health questionnaire. Of 632 (85%) women who had a previous birth, 619 (98%) reported antenatal care attendance. Of these, 491 (79%) subsequently had a facility-based delivery. Factors associated with increased likelihood of facility delivery included respondent's education (odds ratio, OR = 2.0, 95% confidence interval, CI 1.2-3.2, P = 0.004), ideal antenatal care attendance (OR = 2.3, 95% CI 1.4-3.7, P = 0.001) and pregnancy intention (OR = 1.5, 95% CI 1.0-2.2, P = 0.040). Being in a polygamous relationship (OR = 0.6, 95% CI 0.3-0.9, P = 0.024) and having a husband ≥ 40 years (OR = 0.5, 95% CI 0.3-0.9, P = 0.013) were associated with reduced likelihood of facility delivery. Respondent's education (aOR = 1.9, 95% CI 1.1-3.3, P = 0.030) as well as ideal ANC attendance (aOR = 2.0, 95% CI 1.0-3.8, P = 0.040) remained significantly associated with facility delivery in multivariate analyses.}, } @article {pmid30305150, year = {2018}, author = {Manandhar, S and Singh, A and Varma, A and Pandey, S and Shrivastava, N}, title = {Evaluation of methods to detect in vitro biofilm formation by staphylococcal clinical isolates.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {714}, pmid = {30305150}, issn = {1756-0500}, mesh = {Biofilms/*growth & development ; Cross-Sectional Studies ; *Genes, Bacterial ; Genotype ; Humans ; Microbial Sensitivity Tests ; Nepal/epidemiology ; Phenotype ; Staphylococcal Infections/epidemiology/microbiology ; Staphylococcus/*classification/genetics/isolation & purification ; Staphylococcus aureus/*classification/genetics/isolation & purification ; Tertiary Care Centers ; }, abstract = {OBJECTIVE: Staphylococcus genus comprising both Staphylococcus aureus and coagulase negative staphylococci (CoNS) are widely distributed in nature and can infect diversity of hosts. Indeed, staphylococci are the major pathogens causing biofilm associated infections caused by contaminated hospital indwelling devices. These infections are persistent in nature being highly refractory to various stresses including antibiotics. Implementation of efficient diagnostic techniques for the biofilm production would help minimize the disease burden. Thus, early detection of pathogenic strains producing biofilms warrant the utmost importance in diagnostic laboratories especially in resource limited settings.

RESULT: Among 375 isolates collected from different clinical specimens, 214 (57%) were identified as coagulase negative staphylococci and 161 (43%) S. aureus. Detection of In-vitro biofilm formation in these isolates were carried out by three commonly used phenotypic assays and a genotypic assay. While evaluating the results, tissue-culture method with supplemented glucose and sucrose showed the best correlation with the results of genotypic assay.}, } @article {pmid30305145, year = {2018}, author = {Galal, NM and Meshaal, S and ElHawary, R and Nasr, E and Bassiouni, L and Ashghar, H and Farag, NH and Mach, O and Burns, C and Iber, J and Chen, Q and ElMarsafy, A}, title = {Poliovirus excretion following vaccination with live poliovirus vaccine in patients with primary immunodeficiency disorders: clinicians' perspectives in the endgame plan for polio eradication.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {717}, pmid = {30305145}, issn = {1756-0500}, mesh = {Carrier State/immunology/pathology/*virology ; Disease Eradication ; Egypt/epidemiology ; Feces/virology ; Female ; Humans ; Immunologic Deficiency Syndromes/epidemiology/immunology/mortality/*virology ; Infant ; Male ; Poliomyelitis/epidemiology/immunology/prevention & control/*transmission ; Poliovirus/immunology/pathogenicity ; Poliovirus Vaccine, Oral/administration & dosage/*adverse effects ; Public Health Surveillance ; Vaccination/*adverse effects ; *Virus Shedding ; }, abstract = {OBJECTIVE: Primary immunodeficiency (PID) patients are prone to developing viral infections and should not be vaccinated with live vaccines. In such patients, prolonged excretion and viral divergence may occur and they may subsequently act as reservoirs in the community introducing mutated virus and jeopardizing polio eradication. One hundred and thirty PID cases were included for poliovirus detection in stool with assessment of divergence of detected polioviruses from oral polio vaccine (OPV) virus. Clinical presentations of PID patients with detectable poliovirus in stool specimens are described.

RESULTS: Six PID patients (4.5%) had detectable vaccine-derived poliovirus (VDPV) excretion in stool specimens; of these, five patients had severe combined immunodeficiency (two with acute flaccid paralysis, one with meningoencephalitis and two without neurological manifestations), and one patient had X-linked agammaglobulinemia (paralysis developed shortly after diagnosis of immunodeficiency). All six case-patients received trivalent OPV. Five case-patients had type 2 immunodeficiency-related vaccine-derived polioviruses (iVDPV2) excretion; one had concomitant excretion of Sabin like type 3 virus and one was identified as iVDPV1 excretor. Surveillance for poliovirus excretion among PID patients is critical as these patients represent a potential source to reseed polioviruses into populations.}, } @article {pmid30305144, year = {2018}, author = {Syahrul, and Wibowo, S and Haryana, SM and Astuti, I and Nurwidya, F}, title = {The role of insulin receptor substrate 1 gene polymorphism Gly972Arg as a risk factor for ischemic stroke among Indonesian subjects.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {718}, pmid = {30305144}, issn = {1756-0500}, mesh = {Adult ; Aged ; Amino Acid Substitution ; Brain Ischemia/diagnostic imaging/*genetics/pathology ; Case-Control Studies ; Female ; Gene Expression ; Genetic Association Studies ; *Genetic Predisposition to Disease ; Humans ; Indonesia ; Insulin Receptor Substrate Proteins/*genetics ; Insulin Resistance ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Odds Ratio ; *Polymorphism, Genetic ; Risk Factors ; Stroke/diagnostic imaging/*genetics/pathology ; Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: The identification of new genetic-associated risk factor of ischemic stroke could improves strategies for stroke prevention. This study aims to identify insulin receptor substrate 1 (IRS-1) gene polymorphism Gly972Arg as the risk factor for ischemic stroke among Indonesian subjects. The case-control study was conducted by matching the gender and race on 85 cases of patients with ischemic stroke and 86 healthy non-stroke control subjects. Ischemic stroke was established by the complete neurology examination and brain computed tomography scan or magnetic resonance imaging. Polymerase chain reaction-Restriction Fragment Length Polymorphism was performed to analyze IRS-1 gene Gly972Arg genotype.

RESULTS: There were 85 ischemic stroke cases and 86 control subjects. The distribution of nucleotide IRS-1 gene polymorphism Gly972Arg in the ischemic stroke vs health controls for GG were 32.2% vs 41.5%, for GR were 16% vs 7.6%, and for RR were 0.5% vs 1.9%. IRS-1 gene polymorphism Gly972Arg was found as significant risk factor for ischemic stroke [odds ratio of 2.6 (1.27-5.27); CI 95%, p = 0.008]. Conclusively, the IRS-1 gene polymorphism Gly972Arg should be considered as an important factor in the prevention and treatment of ischemic stroke.}, } @article {pmid30305095, year = {2018}, author = {Rosa, JRBF and Mantello, CC and Garcia, D and de Souza, LM and da Silva, CC and Gazaffi, R and da Silva, CC and Toledo-Silva, G and Cubry, P and Garcia, AAF and de Souza, AP and Le Guen, V}, title = {QTL detection for growth and latex production in a full-sib rubber tree population cultivated under suboptimal climate conditions.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {223}, pmid = {30305095}, issn = {1471-2229}, support = {2012/50491-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2011/50188-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2009/52975//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2009/14068-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2013/20447-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 478701/2012-8; 402954/2012-2//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 6087-14-0//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 2343/15-0//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 1102-008//Agropolis Fondation/ ; ANR-10-LABX-001-01 Labex Agro//Agence Nationale de la Recherche/ ; }, mesh = {Brazil ; Climate ; Hevea/*genetics/metabolism ; Latex/*metabolism ; Microsatellite Repeats ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: Rubber tree is cultivated in mainly Southeast Asia and is by far the most significant source of natural rubber production worldwide. However, the genetic architecture underlying the primary agronomic traits of this crop has not been widely characterized. This study aimed to identify quantitative trait loci (QTLs) associated with growth and latex production using a biparental population established in suboptimal growth conditions in Brazil.

RESULTS: A full-sib population composed of 251 individuals was developed from crossing two high-producing Asiatic rubber tree cultivars, PR 255 and PB 217. This mapping population was genotyped with microsatellite markers from enriched genomic libraries or transcriptome datasets and single-nucleotide polymorphism (SNP) markers, leading to construction of a saturated multipoint integrated genetic map containing 354 microsatellite and 151 SNP markers. Height and circumference measurements repeated over a six-year period and registration of cumulative latex production during six consecutive months on the same individuals allowed in-depth characterization of the genetic values of several growth traits and precocious latex production. Growth traits, circumference and height, were overall positively correlated, whereas latex production was not correlated or even negatively correlated with growth traits. A total of 86 distinct QTLs were identified, most of which were detected for only one trait. Among these QTLs, 15 were linked to more than one phenotypic trait (up to 4 traits simultaneously). Latex production and circumference increments during the last wintering period were associated with the highest numbers of identified QTLs (eleven and nine, respectively), jointly explaining the most significantly observed phenotypic variances (44.1% and 44.4%, respectively). The most important QTL for latex production, located on linkage group 16, had an additive effect of the male parent PB 217 and corresponded to a QTL at the same position detected in a previous study carried out in Thailand for the biparental population RRIM 600 x PB 217.

CONCLUSIONS: Our results identified a set of significant QTLs for rubber tree, showing that the performance of modern Asiatic cultivars can still be improved and paving the way for further marker-assisted selection, which could accelerate breeding programs.}, } @article {pmid30305047, year = {2018}, author = {Zhang, X and Su, N and Jia, L and Tian, J and Li, H and Huang, L and Shen, Z and Cui, J}, title = {Transcriptome analysis of radish sprouts hypocotyls reveals the regulatory role of hydrogen-rich water in anthocyanin biosynthesis under UV-A.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {227}, pmid = {30305047}, issn = {1471-2229}, support = {31572169//National Natural Science Foundation of China/ ; }, mesh = {Anthocyanins/*biosynthesis/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Hydrogen/*metabolism ; Hypocotyl/genetics/metabolism ; Molecular Sequence Annotation ; Raphanus/*genetics/*metabolism ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Transcription Factors/genetics/metabolism ; Ultraviolet Rays ; Water/chemistry/metabolism ; }, abstract = {BACKGROUND: Hydrogen gas (H2) is the most abundant element in the universe, and has been reported to act as a novel beneficial gaseous molecule in plant adaptive responses. Radish sprouts are popular because they contain substantial amounts of antioxidants and health-promoting compounds, such as anthocyanin and glucosinolates. Although radish sprouts accumulated more anthocyanin under UV-A after treatment with hydrogen-rich water (HRW), the molecular mechanism responsible is still elusive. To explore these mechanisms, RNA-seq analysis was used.

RESULTS: Four cDNA libraries from radish sprout hypocotyls were constructed, and a total of 14,564 differentially expressed genes (DEGs) were identified through pairwise comparisons. By Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, these unigenes were found to be implicated in light signal perception and transduction, starch and sucrose metabolism, photosynthesis, nitrogen metabolism and biosynthesis of secondary metabolites. The MYB-bHLH-WD40 complex accounted for the majority of the transcription factors found to be involved in anthocyanin biosynthesis, and levels of transcripts for this complex were in accordance with the anthocyanin concentrations observed. In addition, other transcription factors (such as NAC, bZIP and TCP) might participate in HRW-promoted anthocyanin biosynthesis. Furthermore, the signaling processes of plant hormones, MAPKs and Ca2+ might be involved in HRW-promoted anthocyanin biosynthesis under UV-A. The expression patterns of 16 selected genes were confirmed using qRT-PCR analysis.

CONCLUSIONS: Taken together, the results of this study may expand our understanding of HRW-promoted anthocyanin accumulation under UV-A in radish sprouts.}, } @article {pmid30305032, year = {2018}, author = {Yang, C and Shen, W and Chen, H and Chu, L and Xu, Y and Zhou, X and Liu, C and Chen, C and Zeng, J and Liu, J and Li, Q and Gao, C and Charron, JB and Luo, M}, title = {Characterization and subcellular localization of histone deacetylases and their roles in response to abiotic stresses in soybean.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {226}, pmid = {30305032}, issn = {1471-2229}, support = {2017399//Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; 31671467//National Natural Science Foundation of China/ ; 31770048//National Natural Science Foundation of China/ ; C83025//China 1000-Talents Plan for young researchers/ ; 2018A030313350//Natural Science Foundation of Guangdong Province/ ; XDA13020603//the Strategic Priority Research Program of Chinese Academy of Sciences/ ; }, mesh = {Bacterial Proteins/genetics ; Chromosome Mapping ; Gene Duplication ; *Gene Expression Regulation, Plant ; Histone Deacetylases/genetics/*metabolism ; Luminescent Proteins/genetics ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified ; Soybeans/genetics/*physiology ; Stress, Physiological/*physiology ; }, abstract = {BACKGROUND: Histone deacetylases (HDACs) function as key epigenetic factors in repressing the expression of genes in multiple aspects of plant growth, development and plant response to abiotic or biotic stresses. To date, the molecular function of HDACs is well described in Arabidopsis thaliana, but no systematic analysis of this gene family in soybean (Glycine max) has been reported.

RESULTS: In this study, 28 HDAC genes from soybean genome were identified, which were asymmetrically distributed on 12 chromosomes. Phylogenetic analysis demonstrated that GmHDACs fall into three major groups previously named RPD3/HDA1, SIR2, and HD2. Subcellular localization analysis revealed that YFP-tagged GmSRT4, GmHDT2 and GmHDT4 were predominantly localized in the nucleus, whereas GmHDA6, GmHDA13, GmHDA14 and GmHDA16 were found in both the cytoplasm and nucleus. Real-time quantitative PCR showed that GmHDA6, GmHDA13, GmHDA14, GmHDA16 and GmHDT4 were broadly expressed across plant tissues, while GmHDA8, GmSRT2, GmSRT4 and GmHDT2 showed differential expression across various tissues. Interestingly, we measured differential changes in GmHDACs transcripts accumulation in response to several abiotic cues, indicating that these epigenetic modifiers could potentially be part of a dynamic transcriptional response to stress in soybean. Finally, we show that the levels of histone marks previously reported to be associated with plant HDACs are modulated by cold and heat in this legume.

CONCLUSION: We have identified and classified 28 HDAC genes in soybean. Our data provides insights into the evolution of the HDAC gene family and further support the hypothesis that these genes are important for the plant responses to environmental stress.}, } @article {pmid30305031, year = {2018}, author = {Rivera-Osorio, A and Osorio, A and Poggio, S and Dreyfus, G and Camarena, L}, title = {Architecture of divergent flagellar promoters controlled by CtrA in Rhodobacter sphaeroides.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {129}, pmid = {30305031}, issn = {1471-2180}, support = {B2014-235996//CONACyT/ ; PAPIIT-IN204317//DGAPA-UNAM/ ; }, abstract = {BACKGROUND: Rhodobacter sphaeroides has two sets of flagellar genes, fla1 and fla2, that are responsible for the synthesis of two different flagellar structures. The expression of the fla2 genes is under control of CtrA. In several α-proteobacteria CtrA is also required for the expression of the flagellar genes, but the architecture of CtrA-dependent promoters has only been studied in detail in Caulobacter crescentus. In many cases the expression of fla genes originates from divergent promoters located a few base pairs apart, suggesting a particular arrangement of the cis-acting sites.

RESULTS: Here we characterized several control regions of the R. sphaeroides fla2 genes and analyzed in detail two regions containing the divergent promoters flgB2p-fliI2p, and fliL2p-fliF2p. Binding sites for CtrA of these promoters were identified in silico and tested by site directed mutagenesis. We conclude that each one of these promoter regions has a particular arrangement, either a single CtrA binding site for activation of fliL2p and fliF2p, or two independent sites for activation of flgB2p and fliI2p. ChIP experiments confirmed that CtrA binds to the control region containing the flgB2 and fliI2 promoters, supporting the notion that CtrA directly controls the expression of the fla2 genes. The flgB and fliI genes are syntenic and show a short intercistronic region in closely related bacterial species. We analyzed these regions and found that the arrangement of the CtrA binding sites varies considerably.

CONCLUSIONS: The results in this work reveal the arrangement of the fla2 divergent promoters showing that CtrA promotes transcriptional activation using more than a single architecture.}, } @article {pmid30305030, year = {2018}, author = {Luo, P and Yun, L and Li, Y and Tian, Y and Liu, Q and Huang, W and Hu, C}, title = {Complete genomic sequence of the Vibrio alginolyticus bacteriophage Vp670 and characterization of the lysis-related genes, cwlQ and holA.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {741}, pmid = {30305030}, issn = {1471-2164}, support = {A201701B03//the Program of Fishery Problem Tackling of Guangdong Province/ ; 2015B020231007//the Science and Technology Planning Project of Guangdong Province/ ; XDA13000000//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, mesh = {Bacteriophages/*genetics/*physiology ; Genes, Viral/*genetics ; *Genomics ; Phylogeny ; Vibrio alginolyticus/*virology ; Virus Replication/genetics ; }, abstract = {BACKGROUND: Biocontrol of bacterial pathogens by bacteriophages (phages) represents a promising strategy. Vibrio alginolyticus, a gram-negative bacterium, is a notorious pathogen responsible for the loss of economically important farmed marine animals. To date, few V. alginolyticus phages have been successfully isolated, and only three complete genome sequences of them have been released. The limited available phage resources and poor genomic data hamper research on V. alginolyticus phages and their applications for the biocontrol of V. alginolyticus.

RESULTS: We isolated a phage, Vp670, against the V. alginolyticus strain E06333 and obtained its full genomic sequence. It contains 43,121 nucleotides with a GC content of 43.4%, and codes for 49 predicted open reading frames. Observation by electron microscope combined with phylogenetic analysis of DNA polymerase indicates that Vp670 belongs to the subfamily Autographivirinae in the family Podoviridae. orf3 (designated holA) and orf8 (designated cwlQ) are predicted to encode a holin (HolA) and an endolysin (CwlQ), respectively. Expression of holA alone or coexpression of holA and cwlQ from within arrested the growth of Escherichia coli and V. alginolyticus while the expression of cwlQ alone had no effect on the growth of them. Further observation by transmission electron microscopy revealed that the expression of holA vanished the outer membrane and caused the release of cellular contents of V. alginolyticus and the coexpression of holA and cwlQ directly burst the cells and caused a more drastic release of cellular contents. Expression of cwlQ alone in V. alginolyticus did not cause cytomorphological changes.

CONCLUSIONS: Phage Vp670 is a V. alginolyticus phage belonging to the family of Podoviridae. The genome of Vp670 contains a two-component lysis module, which is comprised of holA and cwlQ. holA is predicted to encode for the holin protein, HolA, and cwlQ is predicted to encode for the endolysin protein, CwlQ. Both holA and cwlQ likely play important roles during the release of phage progeny.}, } @article {pmid30305029, year = {2018}, author = {Jeyaraman, M and Robert, PSA}, title = {Bio efficacy of indigenous biological agents and selected fungicides against branch canker disease of (Macrophoma theicola) tea under field level.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {222}, pmid = {30305029}, issn = {1471-2229}, mesh = {Ascomycota/*pathogenicity ; Bacillus amyloliquefaciens ; Beauveria ; Biological Control Agents/*pharmacology ; Camellia sinensis/drug effects/*microbiology ; Copper/pharmacology ; Fungicides, Industrial/*pharmacology ; Gliocladium ; India ; Plant Diseases/microbiology ; Trichoderma ; }, abstract = {BACKGROUND: Branch canker caused by Macrophoma theicola is a major stem disease of tea plants (Camellia spp.). In tea plantations, this disease causes crop loss and it is one of the major limiting factor for yield stagnation. In very few instances it causes considerable damage in new clearings (about 3 or 4 years old) and large number of bushes have been killed. As there is no control measures for branch canker disease in south Indian tea plantation, this field study was conducted in naturally infected pruned tea field at UPASI Tea Research Institute (Good Agricultural Practice), Valparai, Tamil Nadu, India.

METHODS: The chemical fungicides, biological agents and bio products were evaluated under naturally infected field of seedling plants for two consecutive disease seasons (2014-2015) and there was 11 treatments with three applications. All the treatments were carried out in the time of February-March and October-November (2014-2015). The two set of application was conducted per year. Each set contains eight rounds during the month of February-March as well as October-November (2014-2015). The chemical fungicides, biological agents and commercial bio products were measured as per UPASI- TRF, recommendation viz., COC (50 g/ha and 0.2 g/plot), Companion (20 g/ha and 0.08 g/plot), biological agent of Bacillus amyloliquefaciens, Tichoderma harzianum, Gliocladium virens and Beauveria bassiana (5 kg/ha and 20.8 g/plot) and bio product of Tari (1 L/ha and 4.2 ml/plot) and Tricure (1 L/ha and 4.2 ml/plot).

RESULTS: The present investigation revealed the integrated application of Companion/Bacillus amyloliquefaciens showed superior control of branch canker disease followed by the treatment with Companion alone under field condition. Copper oxychloride/Bacillus amyloliquefaciens was moderately effective followed by Copper oxychloride. The significantly reduced canker size was recorded with treatment of Bacillus amyloliquefaciens followed by commercial organic fungicides of Tari (Organic Tea Special) and Tricure (0.03% Azadirachtin). The least canker size was observed with Gliocladium virens followed by Beauveria bassiana. Branch canker disease incidence was increased in untreated control plants when compared to treated plants.

CONCLUSION: Among these 11 treatments, the integrated treatment of companion at rate of 0.08 g and Bacillus amyloliquefaciens (20.8 g) showed the most significantly decreased canker size (DPL, 5.76) followed by another treatment with companion (0.08 g) (DPL, 4.11). The moderate reduction of canker size was observed by the treatment with Copper oxychloride (0.2 g)/Bacillus amyloliquefaciens (20.8 g) (DPL, 3.05) followed by the treatment of copper oxychloride alone (DPL, 1.74). Therefore, the integrated application of Companion/Bacillus amyloliquefaciens proved significantly effective in the management of branch canker disease under the field conditions.}, } @article {pmid30305028, year = {2018}, author = {Osti, JF and Rodrigues, A}, title = {Escovopsioides as a fungal antagonist of the fungus cultivated by leafcutter ants.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {130}, pmid = {30305028}, issn = {1471-2180}, support = {2014/24298-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, abstract = {BACKGROUND: Fungus gardens of fungus-growing (attine) ants harbor complex microbiomes in addition to the mutualistic fungus they cultivate for food. Fungi in the genus Escovopsioides were recently described as members of this microbiome but their role in the ant-fungus symbiosis is poorly known. In this study, we assessed the phylogenetic diversity of 21 Escovopsioides isolates obtained from fungus gardens of leafcutter ants (genera Atta and Acromyrmex) and non-leafcutter ants (genera Trachymyrmex and Apterostigma) sampled from several regions in Brazil.

RESULTS: Regardless of the sample locality or ant genera, phylogenetic analysis showed low genetic diversity among the 20 Escovopsisoides isolates examined, which prompted the identification as Escovopsioides nivea (the only described species in the genus). In contrast, one Escovopsioides isolate obtained from a fungus garden of Apterostigma megacephala was considered a new phylogenetic species. Dual-culture plate assays showed that Escovopsioides isolates inhibited the mycelium growth of Leucoagaricus gongylophorus, the mutualistic fungus cultivated by somes species of leafcutter ants. In addition, Escovopsioides growth experiments in fungus gardens with and without ant workers showed this fungus is detrimental to the ant-fungus symbiosis.

CONCLUSIONS: Here, we provide clues for the antagonism of Escovopsioides towards the mutualistic fungus of leafcutter ants.}, } @article {pmid30305027, year = {2018}, author = {Liu, W and Bai, S and Zhao, N and Jia, S and Li, W and Zhang, L and Wang, J}, title = {Non-target site-based resistance to tribenuron-methyl and essential involved genes in Myosoton aquaticum (L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {225}, pmid = {30305027}, issn = {1471-2229}, support = {No. 31601653//National Natural Science Foundation of China/ ; No.31772181//National Natural Science Foundation of China/ ; No.31471424//National Natural Science Foundation of China/ ; No. 2017M612311//Project funded by China Postdoctoral Science Foundation/ ; No. SYL2017XTTD11//Funds of "Shandong Double" Tops Program/ ; }, mesh = {Acetolactate Synthase/genetics ; Arylsulfonates/*pharmacology ; Caryophyllaceae/*drug effects/genetics/physiology ; Cytochrome P-450 Enzyme System/genetics ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Plant ; *Genes, Essential ; Herbicide Resistance/*physiology ; Herbicides/pharmacology ; Malathion/pharmacology ; Molecular Sequence Annotation ; Mutation ; Plant Proteins/genetics ; Plant Weeds/drug effects/physiology ; Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Water chickweed (Myosoton aquaticum (L.)) is a dicot broadleaf weed that is widespread in winter fields in China, and has evolved serious resistance to acetolactate synthase (ALS) inhibiting herbicides.

RESULTS: We identified a M. aquaticum population exhibiting moderate (6.15-fold) resistance to tribenuron-methyl (TM). Target-site ALS gene sequencing revealed no known resistance mutations in these plants, and the in vitro ALS activity assays showed no differences in enzyme sensitivity between susceptible and resistant populations; however, resistance was reversed by pretreatment with the cytochrome P450 (CYP) monooxygenase inhibitor malathion. An RNA sequencing transcriptome analysis was performed to identify candidate genes involved in metabolic resistance, and the unigenes obtained by de novo transcriptome assembly were annotated across seven databases. In total, 34 differentially expressed genes selected by digital gene expression analysis were validated by quantitative real-time (qRT)-PCR. Ten consistently overexpressed contigs, including four for CYP, four for ATP-binding cassette (ABC) transporter, and two for peroxidase were further validated by qRT-PCR using additional plants from resistant and susceptible populations. Three CYP genes (with homology to CYP734A1, CYP76C1, and CYP86B1) and one ABC transporter gene (with homology to ABCC10) were highly expressed in all resistant plants.

CONCLUSION: The mechanism of TM resistance in M. aquaticum is controlled by NTSR rather than TSR. Four genes, CYP734A1, CYP76C1, CYP86B1, and ABCC10 could play essential role in metabolic resistance to TM and justify further functional studies. To our knowledge, this is the first large-scale transcriptome analysis of genes associated with NTSR in M. aquaticum using the Illumina platform. Our data provide resource for M. aquaticum biology, and will facilitate the study of herbicide resistance mechanism at the molecular level in this species as well as in other weeds.}, } @article {pmid30305026, year = {2018}, author = {Han, BW and Ye, H and Wei, PP and He, B and Han, C and Chen, ZH and Chen, YQ and Wang, WT}, title = {Global identification and characterization of lncRNAs that control inflammation in malignant cholangiocytes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {735}, pmid = {30305026}, issn = {1471-2164}, support = {81772621//NSFC/ ; 81770174//NSFC/ ; }, mesh = {Bile Duct Neoplasms/*genetics/metabolism/pathology ; Carcinogenesis/genetics ; Cholangiocarcinoma/*genetics/metabolism/pathology ; Cytokines/metabolism ; *Gene Expression Profiling ; Humans ; Inflammation/genetics ; Oligonucleotide Array Sequence Analysis ; RNA, Long Noncoding/*genetics ; }, abstract = {BACKGROUND: Long noncoding RNAs (lncRNAs) are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA), a cholangiocyte malignancy with poor prognosis, and associated with chronic inflammation and damage to the biliary epithelium. This study determined whether lncRNAs were dysregulated and participated in disease diagnosis or pivotal inflammation pathways through a genome-wide lncRNA screening and functional analysis.

RESULTS: We firstly identified a large number of lncRNAs abnormally expressed between 9 pairs of cancerous and adjacent tissues of CCA, and between intra-hepatic CCA and extra-hepatic CCA through a genome-wide profiling. A set of aberrant differentially expressed lncRNAs were further validated in a training set (16 pairs) and a test set (11 pairs) of CCA patient samples. Following assessment of the diagnostic value of the 7 differentially expressed lncRNAs, we confirmed the optimal combination of H19, C3P1, AC005550.3, PVT1, and LPAL2 with area under the curve of 0.8828 [95% CI: 0.7441-1.021, P < 0.001], with 93.75% sensitivity and 81.25% specificity, at the cutoff point of - 0.2884 to distinguish the CCA tissue from the normal ones, suggesting that specific lncRNAs may have potential for detecting CCA. More importantly, the genome-wide locus and lncRNA/mRNA co-expression analyses revealed a set of lncRNAs that participated in inflammation and oxidative stress response pathways by regulating genes in cis or in trans. Finally, APOC1P1, PVT1, and LPAL2 were validated to regulate the migration and some pivotal inflammation genes under the CCA pathogenesis.

CONCLUSIONS: Our findings are the first to show that lncRNAs may not only be potential biomarkers of CCA progression but also respond to inflammation in CCA.}, } @article {pmid30305025, year = {2018}, author = {Wang, X and Gao, Q and Wang, W and Wang, X and Lei, C and Zhu, F}, title = {The gut bacteria across life stages in the synanthropic fly Chrysomya megacephala.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {131}, pmid = {30305025}, issn = {1471-2180}, support = {034082//EU-funded project PROteINSECT/ ; 2014PY059//Fundamental Research Funds for the Central Universities/ ; 2014bs01//HZAU-funded Doctoral research project/ ; }, abstract = {BACKGROUND: Gut bacteria are closely associated with host. Chrysomya megacephala, as a vector and resource insect, can transmit various pathogenic bacteria and consume manure to produce biofertilizer and larva biomass. However, the gut bacteria composition and abundance of C. megacephala remain unclear.

RESULTS: Illumina MiSeq platform was used to compare composition of gut bacterial community in eggs, 1-day-old larvae, 5-day-old larvae, pupae, adult females and males by sequencing with variation in V4 region of 16S ribosomal DNA gene. In total, 928 operational taxonomic units (OTUs) were obtained. These OTUs were annotated into 19 phyla, 42 classes, 77 orders, 153 families and 289 genera. More than 0.5% abundance of 32 OTU core genera were found across all life stages. At class level, Alphaproteobacteria, Bacilli, Bacteroidia, Betaproteobacteria, Flavobacteriia and Gammaproteobacteria were the most abundant in C. megacephala. Eight species were identified to have significantly different abundance between 1-d-larvae and 5-day-larvae and took 28.95% of shared species between these two groups. Sex-specific bacterial species were identified that Faecalibacterium prausnitzii was merely present in females, while Rhodococcus fascians was merely present in males.

CONCLUSION: Gut bacteria of C. megacephala varied across life stages. The composition and community structure of the bacterial community differed from young larvae to mature larvae, while that were similar in adult females and males. These data will provide an overall view of bacterial community across life stages in C. megacephala with attention on manure associated and pathogenic bacteria.}, } @article {pmid30305024, year = {2018}, author = {Li, Y and Li, RH and Ran, MX and Zhang, Y and Liang, K and Ren, YN and He, WC and Zhang, M and Zhou, GB and Qazi, IH and Zeng, CJ}, title = {High throughput small RNA and transcriptome sequencing reveal capacitation-related microRNAs and mRNA in boar sperm.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {736}, pmid = {30305024}, issn = {1471-2164}, support = {31570533//National Natural Science Foundation of China/ ; }, mesh = {Animals ; *Gene Expression Profiling ; Gene Ontology ; High-Throughput Nucleotide Sequencing ; Male ; MicroRNAs/*genetics ; RNA, Messenger/genetics ; Sperm Capacitation/*genetics ; Spermatozoa/*metabolism/physiology ; Swine ; }, abstract = {BACKGROUND: Capacitation, a prerequisite for oocyte fertilization, is a complex process involving series of structural and functional changes in sperms such as membrane modifications, modulation of enzyme activities, and protein phosphorylation. In order to penetrate and fertilize an oocyte, mammalian sperms must undergo capacitation. Nevertheless, the process of sperm capacitation remains poorly understood and requires further elucidation. In the current study, via high throughput sequencing, we identified and explored the differentially expressed microRNAs (miRNAs) and mRNAs involved in boar sperm capacitation.

RESULTS: We identified a total of 5342 mRNAs and 204 miRNAs that were differentially expressed in fresh and capacitated boar sperms. From these, 12 miRNAs (8 known and 4 newly identified miRNAs) and their differentially expressed target mRNAs were found to be involved in sperm capacitation-related PI3K-Akt, MAPK, cAMP-PKA and Ca2+signaling pathways.

CONCLUSIONS: Our study is first to provide the complete miRNA and transcriptome profiles of boar sperm. Our findings provide important insights for the understanding of the RNA profile in boar sperm and future elucidation of the underlying molecular mechanism relevant to mammalian sperm capacitation.}, } @article {pmid30305023, year = {2018}, author = {Struck, AK and Dierks, C and Braun, M and Hellige, M and Wagner, A and Oelmaier, B and Beineke, A and Metzger, J and Distl, O}, title = {A recessive lethal chondrodysplasia in a miniature zebu family results from an insertion affecting the chondroitin sulfat domain of aggrecan.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {91}, pmid = {30305023}, issn = {1471-2156}, abstract = {BACKGROUND: Congenital skeletal malformations represent a heterogeneous group of disorders affecting bone and cartilage development. In cattle, particular chondrodysplastic forms have been identified in several miniature breeds. In this study, a phenotypic characterization was performed of an affected Miniature Zebu calf using computed tomography, necropsy and histopathological examinations, whole genome sequencing of the case and its parents on an Illumina NextSeq 500 in 2 × 150 bp paired-end mode and validation using Sanger sequencing and a Kompetitive Allele Specific PCR assay. Samples from the family of an affected Miniature Zebu with bulldog syndrome including parents and siblings, 42 healthy Miniature Zebu not related with members of the herd and 88 individuals from eight different taurine cattle breeds were available for validation.

RESULTS: A bulldog-like Miniature Zebu calf showing a large bulging head, a short and compressed body and extremely short and stocky limbs was delivered after a fetotomy. Computed tomography and necropsy revealed severe craniofacial abnormalities including a shortening of the ventral nasal conchae, a cleft hard palate, rotated limbs as well as malformed and fused vertebrae and ribs. Histopathologic examination showed a disorganization of the physeal cartilage with disorderly arranged chondrocytes in columns and a multifocal closed epiphyseal plate. Whole-genome sequencing of this malformed Miniature Zebu calf, its dam and sire and subsequent comparative sequence analysis revealed a one base pair insertion (ACAN:c.5686insC) located within the cartilage development gene aggrecan (ACAN) exclusively homozygous in the affected calf and heterozygous in its parents. This variant was predicted to cause a frameshift (p.Val1898fsTer9) and thus a truncation of the chondroitin sulfate domain as well as a loss of the C-terminal globular domain of ACAN. It perfectly co-segregated with the lethal bulldog syndrome in Miniature Zebus.

CONCLUSIONS: We found a novel mutation in ACAN causing a recessive lethal chondrodysplasia in Miniature Zebu cattle. A diagnostic test for this mutation is now available for Miniature Zebu breeders preventing further cases of bulldog syndrome by targeted matings. To the authors' best knowledge, this is the first case of a Miniature Zebu associated with an ACAN mutation.}, } @article {pmid30305022, year = {2018}, author = {Ma, G and Zhang, W and Liu, L and Chao, WS and Gu, YQ and Qi, L and Xu, SS and Cai, X}, title = {Cloning and characterization of the homoeologous genes for the Rec8-like meiotic cohesin in polyploid wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {224}, pmid = {30305022}, issn = {1471-2229}, support = {0457356//Directorate for Biological Sciences/ ; }, mesh = {Alleles ; Cell Cycle Proteins/*genetics/metabolism ; Chromosomal Proteins, Non-Histone/*genetics/metabolism ; Chromosome Mapping ; Cloning, Molecular ; Exons ; Gene Expression Regulation, Plant ; Haploidy ; Introns ; Meiosis ; Plant Proteins/*genetics/metabolism ; Polyploidy ; Triticum/*genetics ; }, abstract = {BACKGROUND: Meiosis is a specialized cell division critical for gamete production in the sexual reproduction of eukaryotes. It ensures genome integrity and generates genetic variability as well. The Rec8-like cohesin is a cohesion protein essential for orderly chromosome segregation in meiotic cell division. The Rec8-like genes and cohesins have been cloned and characterized in diploid models, but not in polyploids. The present study aimed to clone the homoeologous genes (homoeoalleles) for Rec8-like cohesin in polyploid wheat, an important food crop for humans, and to characterize their structure and function under a polyploid condition.

RESULTS: We cloned two Rec8-like homoeoalleles from tetraploid wheat (TtRec8-A1 and TtRec8-B1) and one from hexaploid wheat (TaRec8-D1), and performed expression and functional analyses of the homoeoalleles. Also, we identified other two Rec8 homoeoalleles in hexaploid wheat (TaRec8-A1 and TaRec8-B1) and the one in Aegilops tauschii (AetRec8-D1) by referencing the DNA sequences of the Rec8 homoeoalleles cloned in this study. The coding DNA sequences (CDS) of these six Rec8 homoeoalleles are all 1,827 bp in length, encoding 608 amino acids. They differed from each other primarily in introns although single nucleotide polymorphisms were detected in CDS. Substantial difference was observed between the homoeoalleles from the subgenome B (TtRec8-B1 and TaRec8-B1) and those from the subgenomes A and D (TtRec8-A1, TaRec8-A1, and TaRec8-D1). TtRec8-A1 expressed dominantly over TtRec8-B1, but comparably to TaRec8-D1, in polyploid wheat. In addition, we developed the antibody against wheat Rec8 and used the antibody to detect Rec8 cohesin in the Western blotting and subcellular localization analyses.

CONCLUSIONS: The Rec8 homoeoalleles from the subgenomes A and D are transcriptionally more active than the one from the subgenome B in polyploid wheat. The structural variation and differential expression of the Rec8 homoeoalleles indicate a unique cross-genome coordination of the homoeologous genes in polyploid wheat, and imply the distinction of the wheat subgenome B from the subgenomes A and D in the origin and evolution.}, } @article {pmid30305021, year = {2018}, author = {Liu, J and Liang, G and Siegmund, KD and Lewinger, JP}, title = {Data integration by multi-tuning parameter elastic net regression.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {369}, pmid = {30305021}, issn = {1471-2105}, support = {P30 ES007048/ES/NIEHS NIH HHS/United States ; 5P01CA196569//National Cancer Institute/ ; P30 ES07048//National Institute of Environmental Health Sciences/ ; R01 HG006705//National Human Genome Research Institute/ ; P30 CA014089/CA/NCI NIH HHS/United States ; R01 HG006705/HG/NHGRI NIH HHS/United States ; 5P30 CA014089//National Cancer Institute/ ; P01 CA196569/CA/NCI NIH HHS/United States ; }, mesh = {*Data Analysis ; Genomics/*methods ; Humans ; Logistic Models ; Software ; }, abstract = {BACKGROUND: To integrate molecular features from multiple high-throughput platforms in prediction, a regression model that penalizes features from all platforms equally is commonly used. However, data from different platforms are likely to differ in effect sizes, the proportion of predictive features, and correlations structures. Subtle but important features may be missed by shrinking all features equally.

RESULTS: We propose an Elastic net (EN) model with separate tuning parameter penalties for each platform that is fit using standard software. In a comprehensive simulation study, we evaluated the performance of EN logistic regression with multiple tuning penalties. We found that when the number of informative features differs among the platforms, and when there is no notable correlation between the features from different platforms, the multi-tuning parameter EN yields more predictive models. Moreover, the multi-tuning parameter EN is robust, in the sense that there is no loss of predictivity relative to a single tuning parameter EN when features across all platforms have similar effects. We also investigated the performance of multi-tuning parameter EN using real cancer datasets.

CONCLUSION: The proposed multi-tuning parameter EN model, fit using standard penalized regression software, can achieve better prediction in sample classification when integrating multiple genomic platforms, compared to the traditional method where a single penalty parameter is used for all features in different platforms.}, } @article {pmid30305020, year = {2018}, author = {McCoski, SR and Vailes, MT and Owens, CE and Cockrum, RR and Ealy, AD}, title = {Exposure to maternal obesity alters gene expression in the preimplantation ovine conceptus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {737}, pmid = {30305020}, issn = {1471-2164}, support = {208-01-15//Commonwealth Health Research Board/ ; }, mesh = {Animals ; Blastocyst/*metabolism ; Female ; *Gene Expression Profiling ; Male ; *Mothers ; *Obesity ; Pregnancy ; Sheep/*genetics ; }, abstract = {BACKGROUND: Embryonic and fetal exposure to maternal obesity causes several maladaptive morphological and epigenetic changes in exposed offspring. The timing of these events is unclear, but changes can be observed even after a short exposure to maternal obesity around the time of conception. The hypothesis of this work is that maternal obesity influences the ovine preimplantation conceptus early in pregnancy, and this exposure will affect gene expression in embryonic and extraembryonic tissues.

RESULTS: Obese and lean ewe groups were established by overfeeding or normal feeding, respectively. Ewes were then bred to genetically similar rams. Conceptuses were collected at day 14 of gestation. Morphological assessments were made, conceptuses were sexed by genomic PCR analysis, and samples underwent RNA-sequencing analysis. While no obvious morphological differences existed between conceptuses, differentially expressed genes (≥ 2-fold; ≥ 0.2 RPKM; ≤ 0.05 FDR) were detected based on maternal obesity exposure (n = 21). Also, differential effects of maternal obesity were noted on each conceptus sex (n = 347). A large portion of differentially expressed genes were associated with embryogenesis and placental development.

CONCLUSIONS: Findings reveal that the preimplantation ovine conceptus genome responds to maternal obesity in a sex-dependent manner. The sexual dimorphism in response to the maternal environment coupled with changes in placental gene expression may explain aberrations in phenotype observed in offspring derived from obese females.}, } @article {pmid30305019, year = {2018}, author = {Mishra, AK and Duraisamy, GS and Khare, M and Kocábek, T and Jakse, J and Bříza, J and Patzak, J and Sano, T and Matoušek, J}, title = {Genome-wide transcriptome profiling of transgenic hop (Humulus lupulus L.) constitutively overexpressing HlWRKY1 and HlWDR1 transcription factors.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {739}, pmid = {30305019}, issn = {1471-2164}, support = {GACR 13-03037S//Czech Science Foundation (GACR)/ ; RVO:60077344//Institutional support/ ; }, mesh = {Gene Expression ; *Gene Expression Profiling ; *Genomics ; Humulus/*genetics ; Molecular Sequence Annotation ; Plant Proteins/*genetics ; Plants, Genetically Modified ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: The hop plant (Humulus lupulus L.) is a valuable source of several secondary metabolites, such as flavonoids, bitter acids, and essential oils. These compounds are widely implicated in the beer brewing industry and are having potential biomedical applications. Several independent breeding programs around the world have been initiated to develop new cultivars with enriched lupulin and secondary metabolite contents but met with limited success due to several constraints. In the present work, a pioneering attempt has been made to overexpress master regulator binary transcription factor complex formed by HlWRKY1 and HlWDR1 using a plant expression vector to enhance the level of prenylflavonoid and bitter acid content in the hop. Subsequently, we performed transcriptional profiling using high-throughput RNA-Seq technology in leaves of resultant transformants and wild-type hop to gain in-depth information about the genome-wide functional changes induced by HlWRKY1 and HlWDR1 overexpression.

RESULTS: The transgenic WW-lines exhibited an elevated expression of structural and regulatory genes involved in prenylflavonoid and bitter acid biosynthesis pathways. In addition, the comparative transcriptome analysis revealed a total of 522 transcripts involved in 30 pathways, including lipids and amino acids biosynthesis, primary carbon metabolism, phytohormone signaling and stress responses were differentially expressed in WW-transformants. It was apparent from the whole transcriptome sequencing that modulation of primary carbon metabolism and other pathways by HlWRKY1 and HlWDR1 overexpression resulted in enhanced substrate flux towards secondary metabolites pathway. The detailed analyses suggested that none of the pathways or genes, which have a detrimental effect on physiology, growth and development processes, were induced on a genome-wide scale in WW-transgenic lines.

CONCLUSIONS: Taken together, our results suggest that HlWRKY1 and HlWDR1 simultaneous overexpression positively regulates the prenylflavonoid and bitter acid biosynthesis pathways in the hop and thus these transgenes are presented as prospective candidates for achieving enhanced secondary metabolite content in the hop.}, } @article {pmid30305018, year = {2018}, author = {Phillips, MA and Rutledge, GA and Kezos, JN and Greenspan, ZS and Talbott, A and Matty, S and Arain, H and Mueller, LD and Rose, MR and Shahrestani, P}, title = {Effects of evolutionary history on genome wide and phenotypic convergence in Drosophila populations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {743}, pmid = {30305018}, issn = {1471-2164}, mesh = {Animals ; Beauveria/physiology ; Desiccation ; Drosophila melanogaster/*genetics/microbiology/physiology ; *Evolution, Molecular ; Fertility/genetics ; *Genomics ; Heterozygote ; *Phenotype ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Studies combining experimental evolution and next-generation sequencing have found that adaptation in sexually reproducing populations is primarily fueled by standing genetic variation. Consequently, the response to selection is rapid and highly repeatable across replicate populations. Some studies suggest that the response to selection is highly repeatable at both the phenotypic and genomic levels, and that evolutionary history has little impact. Other studies suggest that even when the response to selection is repeatable phenotypically, evolutionary history can have significant impacts at the genomic level. Here we test two hypotheses that may explain this discrepancy. Hypothesis 1: Past intense selection reduces evolutionary repeatability at the genomic and phenotypic levels when conditions change. Hypothesis 2: Previous intense selection does not reduce evolutionary repeatability, but other evolutionary mechanisms may. We test these hypotheses using D. melanogaster populations that were subjected to 260 generations of intense selection for desiccation resistance and have since been under relaxed selection for the past 230 generations.

RESULTS: We find that, with the exception of longevity and to a lesser extent fecundity, 230 generations of relaxed selection has erased the extreme phenotypic differentiation previously found. We also find no signs of genetic fixation, and only limited evidence of genetic differentiation between previously desiccation resistance selected populations and their controls.

CONCLUSION: Our findings suggest that evolution in our system is highly repeatable even when populations have been previously subjected to bouts of extreme selection. We therefore conclude that evolutionary repeatability can overcome past bouts of extreme selection in Drosophila experimental evolution, provided experiments are sufficiently long and populations are not inbred.}, } @article {pmid30305017, year = {2018}, author = {Sevillano, CA and Ten Napel, J and Guimarães, SEF and Silva, FF and Calus, MPL}, title = {Effects of alleles in crossbred pigs estimated for genomic prediction depend on their breed-of-origin.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {740}, pmid = {30305017}, issn = {1471-2164}, support = {W 08.250.102//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, mesh = {*Alleles ; Animals ; *Genomics ; Hybridization, Genetic/*genetics ; Male ; Mutation, Missense ; Polymorphism, Single Nucleotide ; Receptor, Melanocortin, Type 4/genetics ; Swine/*genetics ; }, abstract = {BACKGROUND: This study investigated if the allele effect of a given single nucleotide polymorphism (SNP) for crossbred performance in pigs estimated in a genomic prediction model differs depending on its breed-of-origin, and how these are related to estimated effects for purebred performance.

RESULTS: SNP-allele substitution effects were estimated for a commonly used SNP panel using a genomic best linear unbiased prediction model with breed-specific partial relationship matrices. Estimated breeding values for purebred and crossbred performance were converted to SNP-allele effects by breed-of-origin. Differences between purebred and crossbred, and between breeds-of-origin were evaluated by comparing percentage of variance explained by genomic regions for back fat thickness (BF), average daily gain (ADG), and residual feed intake (RFI). From ten regions explaining most additive genetic variance for crossbred performance, 1 to 5 regions also appeared in the top ten for purebred performance. The proportion of genetic variance explained by a genomic region and the estimated effect of a haplotype in such a region were different depending upon the breed-of-origin. To illustrate underlying mechanisms, we evaluated the estimated effects across breeds-of-origin for haplotypes associated to the melanocortin 4 receptor (MC4R) gene, and for the MC4Rsnp itself which is a missense mutation with a known effect on BF and ADG. Although estimated allele substitution effects of the MC4Rsnp mutation were very similar across breeds, explained genetic variance of haplotypes associated to the MC4R gene using a SNP panel that does not include the mutation, was considerably lower in one of the breeds where the allele frequency of the mutation was the lowest.

CONCLUSIONS: Similar regions explaining similar additive genetic variance were observed across purebred and crossbred performance. Moreover, there was some overlap across breeds-of-origin between regions that explained relatively large proportions of genetic variance for crossbred performance; albeit that the actual proportion of variance deviated across breeds-of-origin. Results based on a missense mutation in MC4R confirmed that even if a causal locus has similar effects across breeds-of-origin, estimated effects and explained variance in its region using a commonly used SNP panel can strongly depend on the allele frequency of the underlying causal mutation.}, } @article {pmid30305015, year = {2018}, author = {Yu, Y and Shi, J and Li, X and Liu, J and Geng, Q and Shi, H and Ke, Y and Sun, Q}, title = {Transcriptome analysis reveals the molecular mechanisms of the defense response to gray leaf spot disease in maize.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {742}, pmid = {30305015}, issn = {1471-2164}, support = {2015DFR31060//International Science & Technology Cooperation Program of China/ ; 2017NZ0007//The Key Research and Development Program of Sichuan/ ; }, mesh = {Ascomycota/physiology ; Carotenoids/metabolism ; Disease Resistance/*genetics ; *Gene Expression Profiling ; Gene Ontology ; Peroxidases/metabolism ; Plant Diseases/*microbiology ; Salicylic Acid/metabolism ; Zea mays/*genetics/immunology/metabolism/*microbiology ; }, abstract = {BACKGROUND: Gray leaf spot (GLS), which is caused by the necrotrophic fungi Cercospora zeae-maydis and Cercospora zeina, is one of the most impactful diseases in maize worldwide. The aim of the present study is to identify the resistance genes and understand the molecular mechanisms for GLS resistance.

RESULTS: Two cultivars, 'Yayu889' and 'Zhenghong532,' which are distinguished as resistant and susceptible cultivars, respectively, were challenged with the GLS disease and a RNA-seq experiment was conducted on infected plants at 81, 89, 91, and 93 days post planting (dap). Compared with the beginning stage at 81 dap, 4666, 1733, and 1166 differentially expressed genes (DEGs) were identified at 89, 91, and 93 dap, respectively, in 'Yayu889,' while relatively fewer, i.e., 4713, 881, and 722 DEGs, were identified in 'Zhenghong532.' Multiple pathways involved in the response of maize to GLS, including 'response to salicylic acid,' 'protein phosphorylation,' 'oxidation-reduction process,' and 'carotenoid biosynthetic process,' were enriched by combining differential expression analysis and Weighted Gene Co-expression Network Analysis (WGCNA). The expression of 12 candidate resistance proteins in these pathways were quantified by the multiple reaction monitoring (MRM) method. This approach identified two candidate resistance proteins, a calmodulin-like protein and a leucine-rich repeat receptor-like protein kinase with SNPs that were located in QTL regions for GLS resistance. Metabolic analysis showed that, compared with 'Zhenghong532,' the amount of salicylic acid (SA) and total carotenoids in 'Yayu889' increased, while peroxidase activity decreased during the early infection stages, suggesting that increased levels of SA, carotenoids, and reactive oxygen species (ROS) may enhance the defense response of 'Yayu889' to GLS.

CONCLUSION: By combining transcriptome and proteome analyses with comparisons of resistance QTL regions, calmodulin-like protein and leucine-rich repeat receptor-like protein kinase were identified as candidate GLS resistance proteins. Moreover, we found that the metabolic pathways for ROS, SA, and carotenoids are especially active in the resistant cultivar. These findings could lead to a better understanding of the GLS resistance mechanisms and facilitate the breeding of GLS-resistant maize cultivars.}, } @article {pmid30305014, year = {2018}, author = {Liu, Y and Wu, F and Zhang, L and Wu, X and Li, D and Xin, J and Xie, J and Kong, F and Wang, W and Wu, Q and Zhang, D and Wang, R and Gao, S and Li, W}, title = {Transcriptional defects and reprogramming barriers in somatic cell nuclear reprogramming as revealed by single-embryo RNA sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {734}, pmid = {30305014}, issn = {1471-2164}, support = {31372273//the National Natural Science Foundation of China/ ; 31201789//the National Natural Science Foundation of China/ ; 31501906//the National Natural Science Foundation of China/ ; gwfxZD2016171//the Leading Talent Introduction and Cultivation Plan Project in Anhui Province Colleges and Universities/ ; gxyqZD2016196//the Leading Talent Introduction and Cultivation Plan Project in Anhui Province Colleges and Universities/ ; [2015]49//Anhui university research innovation platform team project/ ; 2014//the Major Project of Biology Discipline Construction in Anhui Province/ ; }, mesh = {Animals ; Cell Line ; Embryo, Mammalian/*metabolism ; Female ; Mice ; *Nuclear Transfer Techniques ; Phosphorylation ; Protein Kinases/metabolism ; *Sequence Analysis, RNA ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Nuclear reprogramming reinstates totipotency or pluripotency in somatic cells by changing their gene transcription profile. This technology is widely used in medicine, animal husbandry and other industries. However, certain deficiencies severely restrict the applications of this technology.

RESULTS: Using single-embryo RNA-seq, our study provides complete transcriptome blueprints of embryos generated by cumulus cell (CC) donor nuclear transfer (NT), embryos generated by mouse embryonic fibroblast (MEF) donor NT and in vivo embryos at each stage (zygote, 2-cell, 4-cell, 8-cell, morula, and blastocyst). According to the results from further analyses, NT embryos exhibit RNA processing and translation initiation defects during the zygotic genome activation (ZGA) period, and protein kinase activity and protein phosphorylation are defective during blastocyst formation. Two thousand three constant genes are not able to be reprogrammed in CCs and MEFs. Among these constant genes, 136 genes are continuously mis-transcribed throughout all developmental stages. These 136 differential genes may be reprogramming barrier genes (RBGs) and more studies are needed to identify.

CONCLUSIONS: These embryonic transcriptome blueprints provide new data for further mechanistic studies of somatic nuclear reprogramming. These findings may improve the efficiency of somatic cell nuclear transfer.}, } @article {pmid30305013, year = {2018}, author = {Abrams, ZB and Zucker, M and Wang, M and Asiaee Taheri, A and Abruzzo, LV and Coombes, KR}, title = {Thirty biologically interpretable clusters of transcription factors distinguish cancer type.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {738}, pmid = {30305013}, issn = {1471-2164}, support = {P50 CA070907//National Cancer Institute/ ; P50 CA168505/CA/NCI NIH HHS/United States ; R01 CA182905//National Cancer Institute/ ; T15 LM011270//U.S. National Library of Medicine/ ; P50 CA070907/CA/NCI NIH HHS/United States ; R01 CA182905/CA/NCI NIH HHS/United States ; P50 CA016508//National Cancer Institute/ ; T15 LM011270/LM/NLM NIH HHS/United States ; P50 CA168505//National Cancer Institute/ ; }, mesh = {Cluster Analysis ; *Computational Biology ; Gene Expression Profiling ; Neoplasms/*classification/genetics/*metabolism ; Principal Component Analysis ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Transcription factors are essential regulators of gene expression and play critical roles in development, differentiation, and in many cancers. To carry out their regulatory programs, they must cooperate in networks and bind simultaneously to sites in promoter or enhancer regions of genes. We hypothesize that the mRNA co-expression patterns of transcription factors can be used both to learn how they cooperate in networks and to distinguish between cancer types.

RESULTS: We recently developed a new algorithm, Thresher, that combines principal component analysis, outlier filtering, and von Mises-Fisher mixture models to cluster genes (in this case, transcription factors) based on expression, determining the optimal number of clusters in the process. We applied Thresher to the RNA-Seq expression data of 486 transcription factors from more than 10,000 samples of 33 kinds of cancer studied in The Cancer Genome Atlas (TCGA). We found that 30 clusters of transcription factors from a 29-dimensional principal component space were able to distinguish between most cancer types, and could separate tumor samples from normal controls. Moreover, each cluster of transcription factors could be either (i) linked to a tissue-specific expression pattern or (ii) associated with a fundamental biological process such as cell cycle, angiogenesis, apoptosis, or cytoskeleton. Clusters of the second type were more likely also to be associated with embryonically lethal mouse phenotypes.

CONCLUSIONS: Using our approach, we have shown that the mRNA expression patterns of transcription factors contain most of the information needed to distinguish different cancer types. The Thresher method is capable of discovering biologically interpretable clusters of genes. It can potentially be applied to other gene sets, such as signaling pathways, to decompose them into simpler, yet biologically meaningful, components.}, } @article {pmid30305012, year = {2018}, author = {Vitkin, E and Solomon, O and Sultan, S and Yakhini, Z}, title = {Genome-wide analysis of fitness data and its application to improve metabolic models.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {368}, pmid = {30305012}, issn = {1471-2105}, mesh = {Exercise Test/*methods ; Genome-Wide Association Study/*methods ; Genomics/*methods ; Humans ; Models, Biological ; }, abstract = {BACKGROUND: Synthetic biology and related techniques enable genome scale high-throughput investigation of the effect on organism fitness of different gene knock-downs/outs and of other modifications of genomic sequence.

RESULTS: We develop statistical and computational pipelines and frameworks for analyzing high throughput fitness data over a genome scale set of sequence variants. Analyzing data from a high-throughput knock-down/knock-out bacterial study, we investigate differences and determinants of the effect on fitness in different conditions. Comparing fitness vectors of genes, across tens of conditions, we observe that fitness consequences strongly depend on genomic location and more weakly depend on gene sequence similarity and on functional relationships. In analyzing promoter sequences, we identified motifs associated with conditions studied in bacterial media such as Casaminos, D-glucose, Sucrose, and other sugars and amino-acid sources. We also use fitness data to infer genes associated with orphan metabolic reactions in the iJO1366 E. coli metabolic model. To do this, we developed a new computational method that integrates gene fitness and gene expression profiles within a given reaction network neighborhood to associate this reaction with a set of genes that potentially encode the catalyzing proteins. We then apply this approach to predict candidate genes for 107 orphan reactions in iJO1366. Furthermore - we validate our methodology with known reactions using a leave-one-out approach. Specifically, using top-20 candidates selected based on combined fitness and expression datasets, we correctly reconstruct 39.7% of the reactions, as compared to 33% based on fitness and to 26% based on expression separately, and to 4.02% as a random baseline. Our model improvement results include a novel association of a gene to an orphan cytosine nucleosidation reaction.

CONCLUSION: Our pipeline for metabolic modeling shows a clear benefit of using fitness data for predicting genes of orphan reactions. Along with the analysis pipelines we developed, it can be used to analyze similar high-throughput data.}, } @article {pmid30304531, year = {2018}, author = {Urantówka, AD and Kroczak, A and Silva, T and Padrón, RZ and Gallardo, NF and Blanch, J and Blanch, B and Mackiewicz, P}, title = {New Insight into Parrots' Mitogenomes Indicates That Their Ancestor Contained a Duplicated Region.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2989-3009}, pmid = {30304531}, issn = {1537-1719}, abstract = {Mitochondrial genomes of vertebrates are generally thought to evolve under strong selection for size reduction and gene order conservation. Therefore, a growing number of mitogenomes with duplicated regions changes our view on the genome evolution. Among Aves, order Psittaciformes (parrots) is especially noteworthy because of its large morphological, ecological, and taxonomical diversity, which offers an opportunity to study genome evolution in various aspects. Former analyses showed that tandem duplications comprising the control region with adjacent genes are restricted to several lineages in which the duplication occurred independently. However, using an appropriate polymerase chain reaction strategy, we demonstrate that early diverged parrot groups contain mitogenomes with the duplicated region. These findings together with mapping duplication data from other mitogenomes onto parrot phylogeny indicate that the duplication was an ancestral state for Psittaciformes. The state was inherited by main parrot groups and was lost several times in some lineages. The duplicated regions were subjected to concerted evolution with a frequency higher than the rate of speciation. The duplicated control regions may provide a selective advantage due to a more efficient initiation of replication or transcription and a larger number of replicating genomes per organelle, which may lead to a more effective energy production by mitochondria. The mitogenomic duplications were associated with phenotypic features and parrots with the duplicated region can live longer, show larger body mass as well as predispositions to a more active flight. The results have wider implications on the presence of duplications and their evolution in mitogenomes of other avian groups.}, } @article {pmid30304402, year = {2018}, author = {Kandler, NM and Abdul Wahab, MA and Noonan, SHC and Bell, JJ and Davy, SK and Webster, NS and Luter, HM}, title = {In situ responses of the sponge microbiome to ocean acidification.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy205}, pmid = {30304402}, issn = {1574-6941}, abstract = {Climate change is causing rapid changes in reef structure, biodiversity, and function, though most sponges are predicted to tolerate conditions projected for 2100. Sponges maintain intimate relationships with microbial symbionts, with previous studies suggesting that microbial flexibility may be pivotal to success under ocean acidification (OA). We performed a reciprocal transplantation of the coral reef sponges Coelocarteria singaporensis and Stylissa cf. flabelliformis between a control reef site and an adjacent CO2 vent site in Papua New Guinea to explore how the sponge microbiome responds to OA. Microbial communities of C. singaporensis, which differed initially between sites, did not shift towards characteristic control or vent microbiomes, even though relative abundances of Chloroflexi and Cyanobacteria increased and that of Thaumarchaeota decreased 7 months after transplantation to the control site. Microbial communities of S. cf. flabelliformis, which were initially stable between sites, did not respond specifically to transplantation but collectively exhibited a significant change over time, with a relative increase in Thaumarchaeota and decrease in Proteobacteria in all treatment groups. The lack of a community shift upon transplantation to the vent site suggests that microbial flexibility, at least in the adult life-history stage, does not necessarily underpin host survival under OA .}, } @article {pmid30304394, year = {2018}, author = {Lee, CC and Wang, J}, title = {Rapid Expansion of a Highly Germline-Expressed Mariner Element Acquired by Horizontal Transfer in the Fire Ant Genome.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3262-3278}, doi = {10.1093/gbe/evy220}, pmid = {30304394}, issn = {1759-6653}, abstract = {Transposable elements (TEs) are present in almost all organisms and affect the host in various ways. TE activity can increase genomic variation and thereby affect host evolution. Currently active TEs are particularly interesting because they are likely generating new genomic diversity. These active TEs have been poorly studied outside of model organisms. In this study, we aimed to identify currently active TEs of a notorious invasive species, the red imported fire ant Solenopsis invicta. Using RNA profiling of male and female germline tissues, we found that the majority of TE-containing transcripts in the fire ant germline belong to the IS630-Tc1-Mariner superfamily. Subsequent genomic characterization of fire ant mariner content, molecular evolution analysis, and population comparisons revealed a highly expressed and highly polymorphic mariner element that is rapidly expanding in the fire ant genome. Additionally, using comparative genomics of multiple insect species we showed that this mariner has undergone several recent horizontal transfer events (<5.1 My). Our results document a rare case of a currently active TE originating from horizontal transfer.}, } @article {pmid30303477, year = {2018}, author = {Saeng-In, P and Phongsopitanun, W and Savarajara, A and Tanasupawat, S}, title = {Streptomyces lichenis sp. nov., isolated from lichen.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3641-3646}, doi = {10.1099/ijsem.0.003052}, pmid = {30303477}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lichens/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptomyces/*classification/genetics/isolation & purification ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A new actinobacterial strain, LCR6-01T, was isolated from a lichen sample collected from Chiang Rai Province, Thailand. Its taxonomic position was determined using a polyphasic approach. The strain had morphological characteristics and chemotaxonomic properties identical to those of members of the genus Streptomyces. The predominant menaquinones were MK-9(H6) and MK-9(H8). The major fatty acids were anteiso-C15 : 0, iso-C15 : 0, iso-C16 : 0, iso-C14 : 0 and C16 : 0. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, an unidentified phosphoglycolipid, an unidentified phospholipid and an unidentified lipid. The genomic DNA G+C content was 74.5 mol%. Phylogenetic analysis based on 16S rRNA gene sequences suggested that the strain belonged to the genus Streptomyces. The strain showed highest 16S rRNA gene sequence similarity to Streptomyces palmae TBRC 1999T (98.6 %), Streptomyces misionensis JCM 4497T (98.6 %), Streptomyces matensis JCM 4268T (98.5 %), Streptomyces althioticus KCTC 9752T (98.5 %) and Streptomyces wuyuanensis KCTC 29112T (98.4 %). DNA-DNA relatedness values among the strain and closely related Streptomyces species were below 70 %. On the basis of the phenotypic characteristics and genotypic distinctiveness, strain LCR6-01T is considered to represent a novel species of the genus Streptomyces, for which the name Streptomyces lichenis sp. nov. is proposed. The type strain is LCR6-01T (=KCTC 39908T=TISTR 2500T).}, } @article {pmid30303476, year = {2018}, author = {He, RH and Liang, QY and Zhao, JX and Du, ZJ}, title = {Hanstruepera crassostreae sp. nov., a novel marine bacterium of the family Flavobacteriaceae isolated from an oyster.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3647-3651}, doi = {10.1099/ijsem.0.003053}, pmid = {30303476}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; China ; Crassostrea/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, non-motile, aerobic and orange-pigmented marine bacterium, designated strain L53T, was isolated from an oyster sample collected from the coast of Weihai, China (122.0° E 37.5° N). Growth of strain L53T occurred at 4-40 °C (optimum, 33 °C), at pH 6.5-8.0 (optimum, pH 7.5) and with 1.0-7.0 % (w/v) NaCl (optimum, 3.0 %). Phylogenetic analyses based on 16S rRNA gene sequences revealed that strain L53T was closely related to Bizionia echini KCTC 22015T (96.9 %) and Hanstruepera neustonica JCM 19743T (96.1 %). Strain L53T was located in a distinct phyletic lineage in a discrete clade associated with H. neustonica JCM 19743T. The DNA G+C content of strain L53T was 33.5 mol%. The sole menaquinone was MK-6. The polar lipids comprised one phosphatidylethanolamine, four unidentified aminolipids and four unidentified lipids. The major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 0 G. Based on morphological, physiological and molecular properties as well as on phylogenetic distinctiveness, strain L53T should be placed in the genus Hanstruepera as representing a novel species, for which the name Hanstruepera crassostreae sp. nov. is proposed. The type strain is L53T (=KCTC 62247T=MCCC 1H00246T).}, } @article {pmid30303475, year = {2018}, author = {Tsang, CC and Tang, JYM and Fong, JYH and Kinne, J and Lee, HH and Joseph, M and Jose, S and Schuster, RK and Tang, Y and Sivakumar, S and Chen, JHK and Teng, JLL and Lau, SKP and Wernery, U and Woo, PCY}, title = {Ignatzschineria cameli sp. nov., isolated from necrotic foot tissue of dromedaries (Camelus dromedarius) and associated maggots (Wohlfahrtia species) in Dubai.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3627-3634}, doi = {10.1099/ijsem.0.003046}, pmid = {30303475}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Camelus/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Foot/microbiology ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Genes, Bacterial ; Larva/*microbiology ; Necrosis/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sarcophagidae/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; United Arab Emirates ; }, abstract = {Five bacterial strains, UAE-HKU57T, UAE-HKU58, UAE-HKU59, UAE-HKU60 and UAE-HKU61, were isolated in Dubai, UAE, from necrotic foot tissue samples of four dromedaries (Camelus dromedarius) and associated maggots (Wohrlfartia species). They were non-sporulating, Gram-negative, non-motile bacilli. They grew well under aerobic conditions at 37 °C, but not anaerobically. The pH range for growth was pH 7.0-9.0 (optimum, pH 7.5-8.0) and the strains could tolerate NaCl concentrations (w/v) up to 2 % (optimum, 0.5 %). They were catalase- and cytochrome oxidase-positive, but caseinase-, gelatinase- and urease-negative. Their phenotypic characters were distinguishable from other closely related species. Phylogenetic analyses of the almost-complete 16S rRNA gene and partial 23S rRNA gene, gyrB, groEL and recA sequences revealed that the five isolates were most closely related to undescribed Ignatzschineria strain F8392 and Ignatzschineria indica, but in most phylogenies clustered separately from these close relatives. Average nucleotide identity analysis showed that genomes of the five isolates (2.47-2.52 Mb, G+C content 41.71-41.86 mol%) were 98.00-99.97% similar to each other, but ≤87.18 % similar to other Ignatzschineriaspecies/strains. Low DNA relatedness between the five isolates to other Ignatzschineriaspecies/strains was also supported by Genome-to-Genome Distance Calculator analysis. The chemotaxonomic traits of the five strains were highly similar. They were non-susceptible (intermediate or resistant) to tetracycline and resistant to trimethoprim/sulphamethoxazole. The name Ignatzschineria cameli sp. nov. is proposed to accommodate these five strains, with strain UAE-HKU57T (=CCOS1165T=NBRC 113042T) as the type strain.}, } @article {pmid30303474, year = {2018}, author = {Greub, G and Bavoil, P}, title = {International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of Chlamydiae. Minutes of the closed meeting, 7 September 2016, Oxford, UK.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3683-3684}, doi = {10.1099/ijsem.0.003049}, pmid = {30303474}, issn = {1466-5034}, } @article {pmid30303473, year = {2018}, author = {Xu, G and Chang, J and Xue, H and Guo, M and Piao, CG and Li, Y}, title = {Herbaspirillum piri sp. nov., isolated from bark of a pear tree.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3652-3656}, doi = {10.1099/ijsem.0.003050}, pmid = {30303473}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Herbaspirillum/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Plant Bark/*microbiology ; Pyrus/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, motile bacterial strain, shQ-4T, was isolated from a pear tree in Henan Province, China. The strain grew at 10-41 °C, at pH 4.0-8.0 and in the presence of 1-3 % (w/v) NaCl. It shared highest 16S rRNA gene sequence similarity (96.66 %) with Herbaspirillum chlorophenolicum CPW301T. The phylogenetic tree based on 16S rRNA gene sequences showed that strain shQ-4T formed a distinct branch next to reference species in the genus Herbaspirillum. The profile of major polar lipids of strain shQ-4T contained phosphatidylethanolamine (PE), diphosphatidylglycerol (DPG), phosphatidylglycerol (PG) and an unidentified aminophospholipid (APL). The major respiratory quinone was Q-8. The major fatty acids of this strain were C16 : 0, summed feature 3 (C16 : 1ω6c/C16 : 1ω7c), C17 : 0 cyclo and C18 : 0. Strain shQ-4T is considered to represent a novel species of the genus Herbaspirillum, with the proposed name Herbaspirillum piri sp. nov. The type strain is shQ-4T (=CFCC 14641T=KCTC 52804T).}, } @article {pmid30303472, year = {2018}, author = {Yu, Y and Fu, Y and Guo, X and Yan, R and Wang, H and Zhao, J and Wang, X and Zhang, J and Xiang, W}, title = {Streptomyces durbertensis sp. nov., isolated from saline-alkali soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3635-3640}, doi = {10.1099/ijsem.0.003047}, pmid = {30303472}, issn = {1466-5034}, mesh = {Alkalies ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salinity ; Sequence Analysis, DNA ; Soil/chemistry ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel strain of actinobacteria, designated NEAU-S1GS20T, was isolated from a saline-alkali soil collected from Heilongjiang Province, north-east China, and characterized using a polyphasic approach. Strain NEAU-S1GS20T exhibited morphological, cultural and chemotaxonomic features consistent with its classification as representing a member of the genus Streptomyces. Growth occurred at 18‒45 °C, at pH 6.0‒10.0 and in the presence of 10 % (w/v) NaCl. Whole-cell hydrolysates mainly contained glucose and ribose. The predominant menaquinones were MK-9(H4) and MK-9(H6). The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and two unidentified phospholipids. The major cellular fatty acids (>10 %) were iso-C16 : 0, iso-C17 : 0, anteiso-C17 : 0 and C16 : 0. The G+C content of the DNA was 72.8 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain NEAU-S1GS20T formed a distinct clade within the genus Streptomyces and was closely related to Streptomyces xinghaiensis CCTCC AA 208049T (98.4 % similarity), Streptomyces chumphonensis JCM 18522T (98.1 %) and Streptomyces palmae JCM 31289T (98.1 %). Multilocus sequence analysis (MLSA) using five housekeeping genes (atpD, gyrB, recA, rpoB and trpB) showed that the MLSA distance of strain NEAU-S1GS20T to the most closely related species was greater than the 0.007 threshold. A combination of DNA-DNA hybridization results and differences in certain phenotypic characteristics demonstrated that strain NEAU-S1GS20T could be distinguished from its closest phylogenetic relatives. Therefore, strain NEAU-S1GS20T represents a novel species of the genus Streptomyces, for which the name Streptomyces durbertensis sp. nov. is proposed. The type strain is NEAU-S1GS20T (=CCTCC AA 2017006T=DSM 104538T).}, } @article {pmid30302755, year = {2018}, author = {Magneville, C and Ratz, T and Richardson, J and Smiseth, PT}, title = {No evidence of sibling cooperation in the absence of parental care in Nicrophorus vespilloides.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2803-2809}, doi = {10.1111/evo.13622}, pmid = {30302755}, issn = {1558-5646}, support = {//University Of Edinburgh/ ; }, abstract = {Interactions among siblings fall on a continuum with competition and cooperation at opposite ends of the spectrum. Prior work on the burying beetle Nicrophorus vespilloides suggests that parental care shifts the balance between competition and cooperation by masking a density-dependent shift from cooperation to competition. However, these results should be interpreted with caution because they were based on correlational evidence for an association between larval density at dispersal and mean larval mass at dispersal. Here, we test for a causal effect of the initial density of larvae in a brood on the larvae's subsequent performance in the absence of care. We find no effect of the initial larval density on mean larval mass. Thus, our results provide no evidence for sibling cooperation in the absence of care in this species. However, using larval density at dispersal as a predictor of mean larval mass at dispersal, there was a significant correlation between larval density and mean larval mass. Our study highlights the importance of using experimental designs that exclude confounding effects due to shared environmental conditions that otherwise could be misinterpreted as evidence for sibling cooperation.}, } @article {pmid30302555, year = {2019}, author = {Soonsanga, S and Rungrod, A and Audtho, M and Promdonkoy, B}, title = {Tyrosine-776 of Vip3Aa64 from Bacillus thuringiensis is Important for Retained Larvicidal Activity During High-Temperature Storage.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {15-21}, doi = {10.1007/s00284-018-1578-x}, pmid = {30302555}, issn = {1432-0991}, support = {P-16-50913//Cluster and Program Management, National Science and Technology Development Agency, Thailand/ ; }, abstract = {Vip3Aa (vegetative insecticidal protein) secreted by Bacillus thuringiensis (Bt) is highly toxic to lepidopteran insects. The Bt isolate M190 produces Vip3Aa35 at high concentrations, and Vip3Aa35 was found to be very effective against Spodoptera exigua. Unfortunately, the use of Vip3Aa35 in pest control is limited by its short shelf life when stored at high temperatures, retaining activity for only 1 month at 37 °C. To find a more stable alternative, we screened 500 isolates of Bt collected from various locations in Thailand and discovered Bt isolate 294 which produced large amounts of Vip3Aa64 that exhibited high toxicity against S. exigua but could be stored at 37 °C for up to 3 months. Vip3Aa35 and Vip3Aa64 have only nine amino acid differences between them, with six of those residues being located at the C terminus. Vip3Aa35 and Vip3Aa64 chimeras revealed that the C-terminal sequence is important for the retained larvicidal activity observed with Vip3Aa64. Various single amino acid substitutions were created to identify the key amino acids responsible for this stability. A single residue, Tyr776, was found to be solely responsible, with the Vip3Aa35:N776Y acquiring thermostability similar to Vip3Aa64 while the Vip3Aa64:Y776N exhibited Vip3Aa35-like thermostability.}, } @article {pmid30302554, year = {2019}, author = {Chen, S and Cao, P and Lang, F and Wu, Z and Pan, D and Zeng, X and Lian, L}, title = {Adhesion-Related Immunomodulatory Activity of the Screened Lactobacillus plantarum from Sichuan Pickle.}, journal = {Current microbiology}, volume = {76}, number = {1}, pages = {29-36}, doi = {10.1007/s00284-018-1580-3}, pmid = {30302554}, issn = {1432-0991}, support = {31671869//National Natural Science Foundation of China/ ; 31601487//National Natural Science Foundation of China/ ; 31471598//National Natural Science Foundation of China/ ; LY19C200005//Natural Science Foundation of Zhejiang Province (CN)/ ; 2016C10022//Ningbo Municipal Bureau of Science and Technology/ ; ZX2015000928//Open Funding of the Key Laboratory of Animal Protein Deep Processing Technology of Zhejiang/ ; }, abstract = {Lactic acid bacteria are the majority fermentation starter in the traditional fermented foods. In this research, a promising Lactobacillus plantarum was isolated from Sichuan pickle and its adhesion properties were analyzed in simulated gastrointestinal fluid with different methods. Meanwhile, the immunomodulatory effect of this strain was also evaluated in the Caco-2 cells. Results found that adhesion-related mub genes and other genes like lsp and tuf were upregulated in different culture times. Furthermore, L. plantarum cultured at alkaline environment revealed some anti-inflammation activity through inhibited expression of cytokine IL-8 and increased expression of anti-inflammatory cytokine IL-10 in Caco-2 cells. The texture of yogurt after fermented by this kind of isolated strain was also investigated, which provides the foundation for the further development and application of this kind of strain in food production. More investigations need to be carried out to determine whether this probiotic contributes to regulation of intestinal flora and prevention of gut inflammation.}, } @article {pmid30302501, year = {2018}, author = {Akand, EH and Downard, KM}, title = {Ancestral and Compensatory Mutations that Promote Antiviral Resistance in Influenza N1 Neuraminidase Revealed by a Phylonumerics Approach.}, journal = {Journal of molecular evolution}, volume = {86}, number = {8}, pages = {546-553}, pmid = {30302501}, issn = {1432-1432}, abstract = {Implementation of a new phylonumerics approach to construct a mass tree representing over 6000 H1N1 human influenza strains has enabled ancestral and compensatory descendant mutations to be identified in N1 neuraminidase that promote antiviral resistance and restore viral fitness. Adjacent to the H275Y resistance mutation site, mutations S299A and S247N, respectively, lead the evolution of oseltamivir-resistant strains and restore viral fitness to those strains thereafter. Importantly the mass tree phylonumerics approach can identify such mutations globally, without any positional bias, so that functionally linked or compensatory mutations remote in the sequence or structure of the protein can be identified and interrogated. This is achieved using mass map datasets commonly employed for protein identification in proteomics applications, thus avoiding the need for either gene or protein sequences that are central to other phylogenetic methods.}, } @article {pmid30302001, year = {2018}, author = {}, title = {Governments must take heed of latest IPCC assessment.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {163}, doi = {10.1038/d41586-018-06952-7}, pmid = {30302001}, issn = {1476-4687}, mesh = {Animals ; Ecosystem ; Environmental Policy/*legislation & jurisprudence ; *Federal Government ; Global Warming/legislation & jurisprudence/*prevention & control/*statistics & numerical data ; Goals ; *Policy Making ; Politics ; *Research Report ; Time Factors ; }, } @article {pmid30302000, year = {2018}, author = {}, title = {Nobel committees must do more to achieve equality.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {164}, doi = {10.1038/d41586-018-06951-8}, pmid = {30302000}, issn = {1476-4687}, } @article {pmid30301999, year = {2018}, author = {Valian, V}, title = {Two Nobels for women - why so slow?.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {165}, doi = {10.1038/d41586-018-06953-6}, pmid = {30301999}, issn = {1476-4687}, } @article {pmid30301998, year = {2018}, author = {Gies, E}, title = {Fortresses of mud: how to protect the San Francisco Bay Area from rising seas.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {178-180}, doi = {10.1038/d41586-018-06955-4}, pmid = {30301998}, issn = {1476-4687}, } @article {pmid30301997, year = {2018}, author = {Guglielmi, G}, title = {Peer-reviewed homeopathy study sparks uproar in Italy.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {173-174}, doi = {10.1038/d41586-018-06967-0}, pmid = {30301997}, issn = {1476-4687}, } @article {pmid30301995, year = {2018}, author = {Klimburg, A}, title = {Trolling, hacking and the 2016 US presidential election.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {188-189}, doi = {10.1038/d41586-018-06942-9}, pmid = {30301995}, issn = {1476-4687}, } @article {pmid30301994, year = {2018}, author = {Tollefson, J}, title = {IPCC says limiting global warming to 1.5 °C will require drastic action.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {172-173}, doi = {10.1038/d41586-018-06876-2}, pmid = {30301994}, issn = {1476-4687}, } @article {pmid30301993, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {196}, doi = {10.1038/d41586-018-06949-2}, pmid = {30301993}, issn = {1476-4687}, } @article {pmid30301992, year = {2018}, author = {}, title = {Bionic algae barrel through blood to deliver drugs.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {167}, doi = {10.1038/d41586-018-06921-0}, pmid = {30301992}, issn = {1476-4687}, } @article {pmid30301991, year = {2018}, author = {}, title = {How to persuade a reluctant metal to take on a superpower.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {166}, doi = {10.1038/d41586-018-06964-3}, pmid = {30301991}, issn = {1476-4687}, } @article {pmid30301990, year = {2018}, author = {}, title = {Neanderthal liaisons bestowed virus-fighting genes on humans.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {166}, doi = {10.1038/d41586-018-06940-x}, pmid = {30301990}, issn = {1476-4687}, } @article {pmid30301989, year = {2018}, author = {Witze, A}, title = {Europe eyes fleet of tiny CO2-monitoring satellites to track global emissions.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {176-177}, doi = {10.1038/d41586-018-06963-4}, pmid = {30301989}, issn = {1476-4687}, } @article {pmid30301988, year = {2018}, author = {Tollefson, J}, title = {Brazil's presidential election could savage its science.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {171-172}, doi = {10.1038/d41586-018-06917-w}, pmid = {30301988}, issn = {1476-4687}, } @article {pmid30301987, year = {2018}, author = {Else, H}, title = {Architect of bold European open-access plan heads to Washington to garner US support.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {174}, doi = {10.1038/d41586-018-06936-7}, pmid = {30301987}, issn = {1476-4687}, } @article {pmid30301986, year = {2018}, author = {Reardon, S}, title = {Science and the Supreme Court: Cases to watch in 2018.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {175}, doi = {10.1038/d41586-018-06887-z}, pmid = {30301986}, issn = {1476-4687}, } @article {pmid30301985, year = {2018}, author = {}, title = {This miniature drug factory fits on a few lab benches.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {166-167}, doi = {10.1038/d41586-018-06929-6}, pmid = {30301985}, issn = {1476-4687}, } @article {pmid30301984, year = {2018}, author = {Gibney, E and Van Noorden, R and Ledford, H and Castelvecchi, D and Warren, M}, title = {'Test-tube' evolution wins Chemistry Nobel Prize.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {176}, doi = {10.1038/d41586-018-06753-y}, pmid = {30301984}, issn = {1476-4687}, } @article {pmid30301983, year = {2018}, author = {}, title = {Tapeworm DNA hints at discomforts of life in a medieval trading hub.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {167}, doi = {10.1038/d41586-018-06914-z}, pmid = {30301983}, issn = {1476-4687}, } @article {pmid30301982, year = {2018}, author = {}, title = {Gone to the dark side: bacteria thrive 600 metres below Earth's surface.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {167}, doi = {10.1038/d41586-018-06911-2}, pmid = {30301982}, issn = {1476-4687}, } @article {pmid30301981, year = {2018}, author = {}, title = {Extraordinary crystals hold secrets of Earth's infancy.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {167}, doi = {10.1038/d41586-018-06889-x}, pmid = {30301981}, issn = {1476-4687}, } @article {pmid30301977, year = {2018}, author = {York, A}, title = {An expanding fungal tree of life.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {719}, doi = {10.1038/s41579-018-0106-0}, pmid = {30301977}, issn = {1740-1534}, } @article {pmid30301976, year = {2018}, author = {York, A}, title = {A useful by-product.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {719}, doi = {10.1038/s41579-018-0105-1}, pmid = {30301976}, issn = {1740-1534}, } @article {pmid30301975, year = {2018}, author = {York, A}, title = {Plant probiotic supresses bacterial wilt.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {719}, doi = {10.1038/s41579-018-0104-2}, pmid = {30301975}, issn = {1740-1534}, } @article {pmid30301974, year = {2018}, author = {Lamont, RJ and Koo, H and Hajishengallis, G}, title = {The oral microbiota: dynamic communities and host interactions.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {745-759}, pmid = {30301974}, issn = {1740-1534}, support = {R37 DE026152/DE/NIDCR NIH HHS/United States ; R01 DE011111/DE/NIDCR NIH HHS/United States ; R01 DE015254/DE/NIDCR NIH HHS/United States ; R01 DE023193/DE/NIDCR NIH HHS/United States ; R01 DE025220/DE/NIDCR NIH HHS/United States ; R01 DE018023/DE/NIDCR NIH HHS/United States ; R01 DE025848/DE/NIDCR NIH HHS/United States ; R01 DE012505/DE/NIDCR NIH HHS/United States ; P01 AI068730/AI/NIAID NIH HHS/United States ; R01 DE024716/DE/NIDCR NIH HHS/United States ; R01 DE017921/DE/NIDCR NIH HHS/United States ; R01 DE024153/DE/NIDCR NIH HHS/United States ; }, abstract = {The dynamic and polymicrobial oral microbiome is a direct precursor of diseases such as dental caries and periodontitis, two of the most prevalent microbially induced disorders worldwide. Distinct microenvironments at oral barriers harbour unique microbial communities, which are regulated through sophisticated signalling systems and by host and environmental factors. The collective function of microbial communities is a major driver of homeostasis or dysbiosis and ultimately health or disease. Despite different aetiologies, periodontitis and caries are each driven by a feedforward loop between the microbiota and host factors (inflammation and dietary sugars, respectively) that favours the emergence and persistence of dysbiosis. In this Review, we discuss current knowledge and emerging mechanisms governing oral polymicrobial synergy and dysbiosis that have both enhanced our understanding of pathogenic mechanisms and aided the design of innovative therapeutic approaches for oral diseases.}, } @article {pmid30301871, year = {2018}, author = {Dance, A}, title = {Inner Workings: The mysterious parentage of the coveted black truffle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10188-10190}, pmid = {30301871}, issn = {1091-6490}, mesh = {Ascomycota/genetics/*physiology ; Fruiting Bodies, Fungal/genetics/*physiology ; Genome, Fungal ; Reproduction/*physiology ; Spores, Fungal/genetics ; }, } @article {pmid30301810, year = {2018}, author = {Turner, AL and Watson, M and Wilkins, OG and Cato, L and Travers, A and Thomas, JO and Stott, K}, title = {Highly disordered histone H1-DNA model complexes and their condensates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {11964-11969}, pmid = {30301810}, issn = {1091-6490}, support = {BB/D002257/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N022181/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Chromatin/metabolism ; Chromatin Assembly and Disassembly/physiology ; DNA/chemistry ; DNA-Binding Proteins ; Histones/*chemistry/*metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Nucleic Acid Conformation ; Phosphorylation ; Protein Binding ; Protein Conformation ; Protein Processing, Post-Translational ; }, abstract = {Disordered proteins play an essential role in a wide variety of biological processes, and are often posttranslationally modified. One such protein is histone H1; its highly disordered C-terminal tail (CH1) condenses internucleosomal linker DNA in chromatin in a way that is still poorly understood. Moreover, CH1 is phosphorylated in a cell cycle-dependent manner that correlates with changes in the chromatin condensation level. Here we present a model system that recapitulates key aspects of the in vivo process, and also allows a detailed structural and biophysical analysis of the stages before and after condensation. CH1 remains disordered in the DNA-bound state, despite its nanomolar affinity. Phase-separated droplets (coacervates) form, containing higher-order assemblies of CH1/DNA complexes. Phosphorylation at three serine residues, spaced along the length of the tail, has little effect on the local properties of the condensate. However, it dramatically alters higher-order structure in the coacervate and reduces partitioning to the coacervate phase. These observations show that disordered proteins can bind tightly to DNA without a disorder-to-order transition. Importantly, they also provide mechanistic insights into how higher-order structures can be exquisitely sensitive to perturbation by posttranslational modifications, thus broadening the repertoire of mechanisms that might regulate chromatin and other macromolecular assemblies.}, } @article {pmid30301809, year = {2018}, author = {Shi, G and Ozog, S and Torbett, BE and Compton, AA}, title = {mTOR inhibitors lower an intrinsic barrier to virus infection mediated by IFITM3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10069-E10078}, pmid = {30301809}, issn = {1091-6490}, support = {T32 GM007198/GM/NIGMS NIH HHS/United States ; }, mesh = {Antiviral Agents/*pharmacology ; Cell Line ; Cell Line, Tumor ; Endosomes/drug effects/metabolism/virology ; HEK293 Cells ; HeLa Cells ; Host-Pathogen Interactions/drug effects ; Humans ; Membrane Proteins/*metabolism ; Protein Transport/drug effects ; RNA-Binding Proteins/*metabolism ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/*antagonists & inhibitors ; Virus Diseases/*drug therapy/*metabolism/virology ; Virus Internalization/*drug effects ; }, abstract = {Rapamycin and its derivatives are specific inhibitors of mammalian target of rapamycin (mTOR) kinase and, as a result, are well-established immunosuppressants and antitumorigenic agents. Additionally, this class of drug promotes gene delivery by facilitating lentiviral vector entry into cells, revealing its potential to improve gene therapy efforts. However, the precise mechanism was unknown. Here, we report that mTOR inhibitor treatment results in down-regulation of the IFN-induced transmembrane (IFITM) proteins. IFITM proteins, especially IFITM3, are potent inhibitors of virus-cell fusion and are broadly active against a range of pathogenic viruses. We found that the effect of rapamycin treatment on lentiviral transduction is diminished upon IFITM silencing or knockout in primary and transformed cells, and the extent of transduction enhancement depends on basal expression of IFITM proteins, with a major contribution from IFITM3. The effect of rapamycin treatment on IFITM3 manifests at the level of protein, but not mRNA, and is selective, as many other endosome-associated transmembrane proteins are unaffected. Rapamycin-mediated degradation of IFITM3 requires endosomal trafficking, ubiquitination, endosomal sorting complex required for transport (ESCRT) machinery, and lysosomal acidification. Since IFITM proteins exhibit broad antiviral activity, we show that mTOR inhibition also promotes infection by another IFITM-sensitive virus, Influenza A virus, but not infection by Sendai virus, which is IFITM-resistant. Our results identify the molecular basis by which mTOR inhibitors enhance virus entry into cells and reveal a previously unrecognized immunosuppressive feature of these clinically important drugs. In addition, this study uncovers a functional convergence between the mTOR pathway and IFITM proteins at endolysosomal membranes.}, } @article {pmid30301808, year = {2018}, author = {Silva, S and Camino, LP and Aguilera, A}, title = {Human mitochondrial degradosome prevents harmful mitochondrial R loops and mitochondrial genome instability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11024-11029}, pmid = {30301808}, issn = {1091-6490}, mesh = {Cell Line, Tumor ; DEAD-box RNA Helicases/metabolism ; DNA, Mitochondrial/genetics ; DNA, Single-Stranded/genetics ; Endoribonucleases/*genetics ; Exosome Multienzyme Ribonuclease Complex/metabolism ; Genome, Mitochondrial/*genetics ; Genomic Instability/*genetics ; HeLa Cells ; Humans ; Mitochondria/*genetics/metabolism ; Multienzyme Complexes/*genetics ; Polyribonucleotide Nucleotidyltransferase/*genetics ; RNA Helicases/*genetics ; RNA Stability/genetics ; RNA, Double-Stranded/genetics ; Ribonucleases/metabolism ; }, abstract = {R loops are nucleic acid structures comprising an DNA-RNA hybrid and a displaced single-stranded DNA. These structures may occur transiently during transcription, playing essential biological functions. However, persistent R loops may become pathological as they are important drivers of genome instability and have been associated with human diseases. The mitochondrial degradosome is a functionally conserved complex from bacteria to human mitochondria. It is composed of the ATP-dependent RNA and DNA helicase SUV3 and the PNPase ribonuclease, playing a central role in mitochondrial RNA surveillance and degradation. Here we describe a new role for the mitochondrial degradosome in preventing the accumulation of pathological R loops in the mitochondrial DNA, in addition to preventing dsRNA accumulation. Our data indicate that, similar to the molecular mechanisms acting in the nucleus, RNA surveillance mechanisms in the mitochondria are crucial to maintain its genome integrity by counteracting pathological R-loop accumulation.}, } @article {pmid30301807, year = {2018}, author = {Weber, Y and Sinninghe Damsté, JS and Zopfi, J and De Jonge, C and Gilli, A and Schubert, CJ and Lepori, F and Lehmann, MF and Niemann, H}, title = {Redox-dependent niche differentiation provides evidence for multiple bacterial sources of glycerol tetraether lipids in lakes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10926-10931}, pmid = {30301807}, issn = {1091-6490}, mesh = {Bacteria/*metabolism ; Biomass ; Carbon/metabolism ; Carbon Isotopes/metabolism ; Ecology ; Geologic Sediments/microbiology ; Glycerol/*metabolism ; Lakes/*microbiology ; Lipids/*chemistry ; Methane/metabolism ; Oxidation-Reduction ; RNA, Ribosomal, 16S/metabolism ; }, abstract = {Terrestrial paleoclimate archives such as lake sediments are essential for our understanding of the continental climate system and for the modeling of future climate scenarios. However, quantitative proxies for the determination of paleotemperatures are sparse. The relative abundances of certain bacterial lipids, i.e., branched glycerol dialkyl glycerol tetraethers (brGDGTs), respond to changes in environmental temperature, and thus have great potential for climate reconstruction. Their application to lake deposits, however, is hampered by the lack of fundamental knowledge on the ecology of brGDGT-producing microbes in lakes. Here, we show that brGDGTs are synthesized by multiple groups of bacteria thriving under contrasting redox regimes in a deep meromictic Swiss lake (Lake Lugano). This niche partitioning is evidenced by highly distinct brGDGT inventories in oxic vs. anoxic water masses, and corresponding vertical patterns in bacterial 16S rRNA gene abundances, implying that sedimentary brGDGT records are affected by temperature-independent changes in the community composition of their microbial producers. Furthermore, the stable carbon isotope composition (δ13C) of brGDGTs in Lake Lugano and 34 other (peri-)Alpine lakes attests to the widespread heterotrophic incorporation of 13C-depleted, methane-derived biomass at the redox transition zone of mesotrophic to eutrophic lake systems. The brGDGTs produced under such hypoxic/methanotrophic conditions reflect near-bottom water temperatures, and are characterized by comparatively low δ13C values. Depending on climate zone and water depth, lake sediment archives predominated by deeper water/low-13C brGDGTs may provide more reliable records of climate variability than those where brGDGTs derive from terrestrial and/or aquatic sources with distinct temperature imprints.}, } @article {pmid30301806, year = {2018}, author = {Gorelik, A and Gebai, A and Illes, K and Piomelli, D and Nagar, B}, title = {Molecular mechanism of activation of the immunoregulatory amidase NAAA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10032-E10040}, pmid = {30301806}, issn = {1091-6490}, support = {MOP-133535//Canadian Institutes of Health Research/International ; }, mesh = {Amidohydrolases/*metabolism ; Analgesics/pharmacology ; Animals ; Catalytic Domain/drug effects ; Cell Line ; Drug Discovery/methods ; Enzyme Inhibitors/pharmacology ; Ethanolamines/metabolism ; Humans ; Inflammation/metabolism ; Ligands ; Mice ; Pain/drug therapy/metabolism ; Palmitic Acids/metabolism ; Rabbits ; Sf9 Cells ; Structure-Activity Relationship ; }, abstract = {Palmitoylethanolamide is a bioactive lipid that strongly alleviates pain and inflammation in animal models and in humans. Its signaling activity is terminated through degradation by N-acylethanolamine acid amidase (NAAA), a cysteine hydrolase expressed at high levels in immune cells. Pharmacological inhibitors of NAAA activity exert profound analgesic and antiinflammatory effects in rodent models, pointing to this protein as a potential target for therapeutic drug discovery. To facilitate these efforts and to better understand the molecular mechanism of action of NAAA, we determined crystal structures of this enzyme in various activation states and in complex with several ligands, including both a covalent and a reversible inhibitor. Self-proteolysis exposes the otherwise buried active site of NAAA to allow catalysis. Formation of a stable substrate- or inhibitor-binding site appears to be conformationally coupled to the interaction of a pair of hydrophobic helices in the enzyme with lipid membranes, resulting in the creation of a linear hydrophobic cavity near the active site that accommodates the ligand's acyl chain.}, } @article {pmid30301805, year = {2018}, author = {van der Kooij, MA and Jene, T and Treccani, G and Miederer, I and Hasch, A and Voelxen, N and Walenta, S and Müller, MB}, title = {Chronic social stress-induced hyperglycemia in mice couples individual stress susceptibility to impaired spatial memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10187-E10196}, pmid = {30301805}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/drug effects/*physiology ; Benzhydryl Compounds/pharmacology ; Brain/metabolism/physiopathology ; Chronic Disease/drug therapy/*psychology ; Glucose/metabolism ; Glucosides/pharmacology ; Hyperglycemia/drug therapy/metabolism/*physiopathology/psychology ; Male ; Memory Disorders/drug therapy/metabolism/*physiopathology/psychology ; Mice ; Mice, Inbred C57BL ; Social Desirability ; Spatial Memory/drug effects/*physiology ; Stress, Psychological/drug therapy/metabolism/*physiopathology/psychology ; }, abstract = {Stringent glucose demands render the brain susceptible to disturbances in the supply of this main source of energy, and chronic stress may constitute such a disruption. However, whether stress-associated cognitive impairments may arise from disturbed glucose regulation remains unclear. Here we show that chronic social defeat (CSD) stress in adult male mice induces hyperglycemia and directly affects spatial memory performance. Stressed mice developed hyperglycemia and impaired glucose metabolism peripherally as well as in the brain (demonstrated by PET and induced metabolic bioluminescence imaging), which was accompanied by hippocampus-related spatial memory impairments. Importantly, the cognitive and metabolic phenotype pertained to a subset of stressed mice and could be linked to early hyperglycemia 2 days post-CSD. Based on this criterion, ∼40% of the stressed mice had a high-glucose (glucose >150 mg/dL), stress-susceptible phenotype. The relevance of this biomarker emerges from the effects of the glucose-lowering sodium glucose cotransporter 2 inhibitor empagliflozin, because upon dietary treatment, mice identified as having high glucose demonstrated restored spatial memory and normalized glucose metabolism. Conversely, reducing glucose levels by empagliflozin in mice that did not display stress-induced hyperglycemia (resilient mice) impaired their default-intact spatial memory performance. We conclude that hyperglycemia developing early after chronic stress threatens long-term glucose homeostasis and causes spatial memory dysfunction. Our findings may explain the comorbidity between stress-related and metabolic disorders, such as depression and diabetes, and suggest that cognitive impairments in both types of disorders could originate from excessive cerebral glucose accumulation.}, } @article {pmid30301804, year = {2018}, author = {Mende, F and Hundahl, C and Plouffe, B and Skov, LJ and Sivertsen, B and Madsen, AN and Lückmann, M and Diep, TA and Offermanns, S and Frimurer, TM and Bouvier, M and Holst, B}, title = {Translating biased signaling in the ghrelin receptor system into differential in vivo functions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10255-E10264}, pmid = {30301804}, issn = {1091-6490}, support = {FDN148431//Canadian Institute for Health Research/International ; }, mesh = {Animals ; Eating/drug effects ; GTP-Binding Proteins/metabolism ; Ghrelin/*metabolism ; HEK293 Cells ; Humans ; Ligands ; Male ; Mice ; Piperidines/pharmacology ; Quinazolinones/pharmacology ; Rats ; Rats, Sprague-Dawley ; Receptors, Ghrelin/*metabolism ; Signal Transduction/drug effects/physiology ; beta-Arrestins/metabolism ; }, abstract = {Biased signaling has been suggested as a means of selectively modulating a limited fraction of the signaling pathways for G-protein-coupled receptor family members. Hence, biased ligands may allow modulation of only the desired physiological functions and not elicit undesired effects associated with pharmacological treatments. The ghrelin receptor is a highly sought antiobesity target, since the gut hormone ghrelin in humans has been shown to increase both food intake and fat accumulation. However, it also modulates mood, behavior, growth hormone secretion, and gastric motility. Thus, blocking all pathways of this receptor may give rise to potential side effects. In the present study, we describe a highly promiscuous signaling capacity for the ghrelin receptor. We tested selected ligands for their ability to regulate the various pathways engaged by the receptor. Among those, a biased ligand, YIL781, was found to activate the Gαq/11 and Gα12 pathways selectively without affecting the engagement of β-arrestin or other G proteins. YIL781 was further characterized for its in vivo physiological functions. In combination with the use of mice in which Gαq/11 was selectively deleted in the appetite-regulating AgRP neurons, this biased ligand allowed us to demonstrate that selective blockade of Gαq/11, without antagonism at β-arrestin or other G-protein coupling is sufficient to decrease food intake.}, } @article {pmid30301803, year = {2018}, author = {Crickard, JB and Kaniecki, K and Kwon, Y and Sung, P and Greene, EC}, title = {Meiosis-specific recombinase Dmc1 is a potent inhibitor of the Srs2 antirecombinase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10041-E10048}, pmid = {30301803}, issn = {1091-6490}, support = {P01 CA092584/CA/NCI NIH HHS/United States ; R01 ES007061/ES/NIEHS NIH HHS/United States ; R01 ES015632/ES/NIEHS NIH HHS/United States ; R35 GM118026/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/metabolism ; Cell Cycle Proteins/*metabolism ; Chromosome Segregation/drug effects ; DNA Helicases/*metabolism ; DNA-Binding Proteins/*metabolism ; Homologous Recombination/drug effects ; Meiosis/*drug effects ; Recombinases/*metabolism ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {Cross-over recombination products are a hallmark of meiosis because they are necessary for accurate chromosome segregation and they also allow for increased genetic diversity during sexual reproduction. However, cross-overs can also cause gross chromosomal rearrangements and are therefore normally down-regulated during mitotic growth. The mechanisms that enhance cross-over product formation upon entry into meiosis remain poorly understood. In Saccharomyces cerevisiae, the Superfamily 1 (Sf1) helicase Srs2, which is an ATP hydrolysis-dependent motor protein that actively dismantles recombination intermediates, promotes synthesis-dependent strand annealing, the result of which is a reduction in cross-over recombination products. Here, we show that the meiosis-specific recombinase Dmc1 is a potent inhibitor of Srs2. Biochemical and single-molecule assays demonstrate that Dmc1 acts by inhibiting Srs2 ATP hydrolysis activity, which prevents the motor protein from undergoing ATP hydrolysis-dependent translocation on Dmc1-bound recombination intermediates. We propose a model in which Dmc1 helps contribute to cross-over formation during meiosis by antagonizing the antirecombinase activity of Srs2.}, } @article {pmid30301802, year = {2018}, author = {Dubois, V and Viljoen, A and Laencina, L and Le Moigne, V and Bernut, A and Dubar, F and Blaise, M and Gaillard, JL and Guérardel, Y and Kremer, L and Herrmann, JL and Girard-Misguich, F}, title = {MmpL8MAB controls Mycobacterium abscessus virulence and production of a previously unknown glycolipid family.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10147-E10156}, pmid = {30301802}, issn = {1091-6490}, mesh = {Amoeba/microbiology ; Animals ; Bacterial Proteins/*metabolism ; Biological Transport/physiology ; Cell Line ; Cytosol/metabolism ; Glycolipids/*metabolism ; Humans ; Lipids ; Macrophages/metabolism/microbiology ; Membrane Proteins/metabolism ; Mice ; Mycobacterium abscessus/*metabolism ; Phagosomes/microbiology ; Virulence/*physiology ; Virulence Factors/*metabolism ; Zebrafish/microbiology ; }, abstract = {Mycobacterium abscessus is a peculiar rapid-growing Mycobacterium (RGM) capable of surviving within eukaryotic cells thanks to an arsenal of virulence genes also found in slow-growing mycobacteria (SGM), such as Mycobacterium tuberculosis A screen based on the intracellular survival in amoebae and macrophages (MΦ) of an M. abscessus transposon mutant library revealed the important role of MAB_0855, a yet uncharacterized Mycobacterial membrane protein Large (MmpL). Large-scale comparisons with SGM and RGM genomes uncovered MmpL12 proteins as putative orthologs of MAB_0855 and a locus-scale synteny between the MAB_0855 and Mycobacterium chelonae mmpL8 loci. A KO mutant of the MAB_0855 gene, designated herein as mmpL8MAB , had impaired adhesion to MΦ and displayed a decreased intracellular viability. Despite retaining the ability to block phagosomal acidification, like the WT strain, the mmpL8MAB mutant was delayed in damaging the phagosomal membrane and in making contact with the cytosol. Virulence attenuation of the mutant was confirmed in vivo by impaired zebrafish killing and a diminished propensity to induce granuloma formation. The previously shown role of MmpL in lipid transport prompted us to investigate the potential lipid substrates of MmpL8MAB Systematic lipid analysis revealed that MmpL8MAB was required for the proper expression of a glycolipid entity, a glycosyl diacylated nonadecyl diol (GDND) alcohol comprising different combinations of oleic and stearic acids. This study shows the importance of MmpL8MAB in modifying interactions between the bacteria and phagocytic cells and in the production of a previously unknown glycolipid family.}, } @article {pmid30301801, year = {2018}, author = {Kokotos, AC and Peltier, J and Davenport, EC and Trost, M and Cousin, MA}, title = {Activity-dependent bulk endocytosis proteome reveals a key presynaptic role for the monomeric GTPase Rab11.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10177-E10186}, pmid = {30301801}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 204954/Z/16/Z//Wellcome Trust/United Kingdom ; MC_UU_12016/5//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cytoskeleton/physiology ; Endocytosis/*physiology ; Endosomes/metabolism/physiology ; Female ; Nanoparticles/metabolism ; Neurons/metabolism/physiology ; Protein Transport/physiology ; Proteome/*metabolism ; Proteomics/methods ; Rats ; Rats, Sprague-Dawley ; Synaptic Transmission/physiology ; Synaptic Vesicles/*metabolism ; rab GTP-Binding Proteins/*metabolism ; }, abstract = {Activity-dependent bulk endocytosis (ADBE) is the dominant mode of synaptic vesicle endocytosis during high-frequency stimulation, suggesting it should play key roles in neurotransmission during periods of intense neuronal activity. However, efforts in elucidating the physiological role of ADBE have been hampered by the lack of identified molecules which are unique to this endocytosis mode. To address this, we performed proteomic analysis on purified bulk endosomes, which are a key organelle in ADBE. Bulk endosomes were enriched via two independent approaches, a classical subcellular fractionation method and isolation via magnetic nanoparticles. There was a 77% overlap in proteins identified via the two protocols, and these molecules formed the ADBE core proteome. Bioinformatic analysis revealed a strong enrichment in cell adhesion and cytoskeletal and signaling molecules, in addition to expected synaptic and trafficking proteins. Network analysis identified Rab GTPases as a central hub within the ADBE proteome. Subsequent investigation of a subset of these Rabs revealed that Rab11 both facilitated ADBE and accelerated clathrin-mediated endocytosis. These findings suggest that the ADBE proteome will provide a rich resource for the future study of presynaptic function, and identify Rab11 as a regulator of presynaptic function.}, } @article {pmid30301800, year = {2018}, author = {Yang, Z and Li, Q and Wang, X and Jiang, X and Zhao, D and Lin, X and He, F and Tang, L}, title = {C-type lectin receptor LSECtin-mediated apoptotic cell clearance by macrophages directs intestinal repair in experimental colitis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11054-11059}, pmid = {30301800}, issn = {1091-6490}, mesh = {Animals ; Apoptosis/*physiology ; Cell Proliferation/physiology ; Colitis/*metabolism/pathology ; Colon/metabolism/pathology ; Disease Models, Animal ; Epithelial Cells/metabolism/pathology ; Inflammatory Bowel Diseases/metabolism/pathology ; Intestinal Mucosa/metabolism/pathology ; Lectins, C-Type/*metabolism ; Macrophages/*metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Phagocytosis/physiology ; Receptors, Virus/*metabolism ; Signal Transduction/physiology ; }, abstract = {Epithelial barrier disruption is a major cause of inflammatory bowel disease (IBD); however, the cellular and molecular regulation of intestinal epithelial homeostasis remains largely undefined. Here, we show that the C-type lectin receptor LSECtin (Clec4g) on macrophages is required for protection against dextran sulfate sodium-induced colitis. Mechanistically, LSECtin promotes apoptotic cell clearance by macrophages and induces the production of antiinflammatory/tissue repair factors in an engulfment-dependent manner, which in turn stimulates epithelial cell proliferation. Deletion of LSECtin results in defective engulfment by colon macrophages, leading to aberrant proresolving factor production and impaired intestinal epithelium repair. Collectively, our findings suggest that LSECtin-dependent corpse clearance by macrophages can direct intestinal regeneration and maintenance of the mucosal barrier after injury.}, } @article {pmid30301799, year = {2018}, author = {Katsumura, KR and Mehta, C and Hewitt, KJ and Soukup, AA and Fraga de Andrade, I and Ranheim, EA and Johnson, KD and Bresnick, EH}, title = {Human leukemia mutations corrupt but do not abrogate GATA-2 function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10109-E10118}, pmid = {30301799}, issn = {1091-6490}, support = {R01 DK050107/DK/NIDDK NIH HHS/United States ; P30 CA014520/CA/NCI NIH HHS/United States ; K01 DK113117/DK/NIDDK NIH HHS/United States ; R01 DK068634/DK/NIDDK NIH HHS/United States ; R37 DK050107/DK/NIDDK NIH HHS/United States ; R56 DK068634/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; GATA2 Transcription Factor/*genetics ; Gene Expression Regulation/genetics ; Haploinsufficiency/genetics ; Hematopoiesis/genetics ; Humans ; Leukemia, Myeloid, Acute/*genetics ; Mice ; Mutation/*genetics ; Myelodysplastic Syndromes/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; Stem Cells/metabolism ; Zinc Fingers/genetics ; }, abstract = {By inducing the generation and function of hematopoietic stem and progenitor cells, the master regulator of hematopoiesis GATA-2 controls the production of all blood cell types. Heterozygous GATA2 mutations cause immunodeficiency, myelodysplastic syndrome, and acute myeloid leukemia. GATA2 disease mutations commonly disrupt amino acid residues that mediate DNA binding or cis-elements within a vital GATA2 intronic enhancer, suggesting a haploinsufficiency mechanism of pathogenesis. Mutations also occur in GATA2 coding regions distinct from the DNA-binding carboxyl-terminal zinc finger (C-finger), including the amino-terminal zinc finger (N-finger), and N-finger function is not established. Whether distinct mutations differentially impact GATA-2 mechanisms is unknown. Here, we demonstrate that N-finger mutations decreased GATA-2 chromatin occupancy and attenuated target gene regulation. We developed a genetic complementation assay to quantify GATA-2 function in myeloid progenitor cells from Gata2 -77 enhancer-mutant mice. GATA-2 complementation increased erythroid and myeloid differentiation. While GATA-2 disease mutants were not competent to induce erythroid differentiation of Lin-Kit+ myeloid progenitors, unexpectedly, they promoted myeloid differentiation and proliferation. As the myelopoiesis-promoting activity of GATA-2 mutants exceeded that of GATA-2, GATA2 disease mutations are not strictly inhibitory. Thus, we propose that the haploinsufficiency paradigm does not fully explain GATA-2-linked pathogenesis, and an amalgamation of qualitative and quantitative defects instigated by GATA2 mutations underlies the complex phenotypes of GATA-2-dependent pathologies.}, } @article {pmid30301798, year = {2018}, author = {Rogers, JM and Passioura, T and Suga, H}, title = {Nonproteinogenic deep mutational scanning of linear and cyclic peptides.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10959-10964}, pmid = {30301798}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Amino Acids/genetics ; Genetic Code/genetics ; Peptides, Cyclic/*genetics ; Protein Binding/genetics ; Proteins/genetics ; Structure-Activity Relationship ; Thermodynamics ; }, abstract = {High-resolution structure-activity analysis of polypeptides requires amino acid structures that are not present in the universal genetic code. Examination of peptide and protein interactions with this resolution has been limited by the need to individually synthesize and test peptides containing nonproteinogenic amino acids. We describe a method to scan entire peptide sequences with multiple nonproteinogenic amino acids and, in parallel, determine the thermodynamics of binding to a partner protein. By coupling genetic code reprogramming to deep mutational scanning, any number of amino acids can be exhaustively substituted into peptides, and single experiments can return all free energy changes of binding. We validate this approach by scanning two model protein-binding peptides with 21 diverse nonproteinogenic amino acids. Dense structure-activity maps were produced at the resolution of single aliphatic atom insertions and deletions. This permits rapid interrogation of interaction interfaces, as well as optimization of affinity, fine-tuning of physical properties, and systematic assessment of nonproteinogenic amino acids in binding and folding.}, } @article {pmid30301797, year = {2018}, author = {Li, S and Roy, P and Travesset, A and Zandi, R}, title = {Why large icosahedral viruses need scaffolding proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10971-10976}, pmid = {30301797}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Capsid/*metabolism ; Capsid Proteins/*metabolism ; Elasticity/physiology ; Virus Assembly/physiology ; Viruses/*metabolism ; }, abstract = {While small single-stranded viral shells encapsidate their genome spontaneously, many large viruses, such as the herpes simplex virus or infectious bursal disease virus (IBDV), typically require a template, consisting of either scaffolding proteins or an inner core. Despite the proliferation of large viruses in nature, the mechanisms by which hundreds or thousands of proteins assemble to form structures with icosahedral order (IO) is completely unknown. Using continuum elasticity theory, we study the growth of large viral shells (capsids) and show that a nonspecific template not only selects the radius of the capsid, but also leads to the error-free assembly of protein subunits into capsids with universal IO. We prove that as a spherical cap grows, there is a deep potential well at the locations of disclinations that later in the assembly process will become the vertices of an icosahedron. Furthermore, we introduce a minimal model and simulate the assembly of a viral shell around a template under nonequilibrium conditions and find a perfect match between the results of continuum elasticity theory and the numerical simulations. Besides explaining available experimental results, we provide a number of predictions. Implications for other problems in spherical crystals are also discussed.}, } @article {pmid30301796, year = {2018}, author = {Dewhirst, MW}, title = {A potential solution for eliminating hypoxia as a cause for radioresistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10548-10550}, pmid = {30301796}, issn = {1091-6490}, mesh = {Cell Hypoxia ; Cell Line, Tumor ; Humans ; *Hypoxia ; *Radiation Tolerance ; }, } @article {pmid30301795, year = {2018}, author = {Brunk, E and Chang, RL and Xia, J and Hefzi, H and Yurkovich, JT and Kim, D and Buckmiller, E and Wang, HH and Cho, BK and Yang, C and Palsson, BO and Church, GM and Lewis, NE}, title = {Characterizing posttranslational modifications in prokaryotic metabolism using a multiscale workflow.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11096-11101}, pmid = {30301795}, issn = {1091-6490}, support = {R01 GM057089/GM/NIGMS NIH HHS/United States ; R35 GM119850/GM/NIGMS NIH HHS/United States ; }, mesh = {Escherichia coli/metabolism ; Gene Editing/methods ; Metabolic Engineering/methods ; Prokaryotic Cells/*metabolism ; Protein Processing, Post-Translational/*genetics/physiology ; Proteins/metabolism ; Workflow ; }, abstract = {Understanding the complex interactions of protein posttranslational modifications (PTMs) represents a major challenge in metabolic engineering, synthetic biology, and the biomedical sciences. Here, we present a workflow that integrates multiplex automated genome editing (MAGE), genome-scale metabolic modeling, and atomistic molecular dynamics to study the effects of PTMs on metabolic enzymes and microbial fitness. This workflow incorporates complementary approaches across scientific disciplines; provides molecular insight into how PTMs influence cellular fitness during nutrient shifts; and demonstrates how mechanistic details of PTMs can be explored at different biological scales. As a proof of concept, we present a global analysis of PTMs on enzymes in the metabolic network of Escherichia coli Based on our workflow results, we conduct a more detailed, mechanistic analysis of the PTMs in three proteins: enolase, serine hydroxymethyltransferase, and transaldolase. Application of this workflow identified the roles of specific PTMs in observed experimental phenomena and demonstrated how individual PTMs regulate enzymes, pathways, and, ultimately, cell phenotypes.}, } @article {pmid30301794, year = {2018}, author = {Sharp, TA and Thomas, SL and Cubuk, ED and Schoenholz, SS and Srolovitz, DJ and Liu, AJ}, title = {Machine learning determination of atomic dynamics at grain boundaries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10943-10947}, pmid = {30301794}, issn = {1091-6490}, abstract = {In polycrystalline materials, grain boundaries are sites of enhanced atomic motion, but the complexity of the atomic structures within a grain boundary network makes it difficult to link the structure and atomic dynamics. Here, we use a machine learning technique to establish a connection between local structure and dynamics of these materials. Following previous work on bulk glassy materials, we define a purely structural quantity (softness) that captures the propensity of an atom to rearrange. This approach correctly identifies crystalline regions, stacking faults, and twin boundaries as having low likelihood of atomic rearrangements while finding a large variability within high-energy grain boundaries. As has been found in glasses, the probability that atoms of a given softness will rearrange is nearly Arrhenius. This indicates a well-defined energy barrier as well as a well-defined prefactor for the Arrhenius form for atoms of a given softness. The decrease in the prefactor for low-softness atoms indicates that variations in entropy exhibit a dominant influence on the atomic dynamics in grain boundaries.}, } @article {pmid30301793, year = {2018}, author = {Liang, W and Li, Q and Ferrara, N}, title = {Metastatic growth instructed by neutrophil-derived transferrin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11060-11065}, pmid = {30301793}, issn = {1091-6490}, mesh = {Animals ; Breast Neoplasms/metabolism/pathology ; Cell Proliferation/*physiology ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Humans ; Lung Neoplasms/metabolism/pathology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasm Metastasis/*pathology ; Neovascularization, Pathologic/metabolism/pathology ; Neutrophils/*metabolism/*pathology ; Receptors, Transferrin/metabolism ; Transferrin/*metabolism ; }, abstract = {The tumor-promoting functions of neutrophils have been mainly attributed to induction of tumor angiogenesis or suppression of anticancer immunity. However, a direct impact of neutrophils on tumor cell growth and metastasis remains largely uncharacterized. Here, we coupled a proteomic approach with a functional screen to interrogate the secretome of tumor-associated neutrophils. Surprisingly, the iron-transporting protein transferrin was identified as the major mitogen for tumor cells secreted by neutrophils. Depletion of neutrophils inhibited lung metastasis and transferrin production in the metastatic microenvironment. Deletion of transferrin receptor suppressed growth of lung-colonizing tumor cells. Also, media conditioned by neutrophils isolated from metastatic breast cancer patients stimulated growth of human breast cancer cells, an effect that was largely abolished by transferrin immunodepletion. We identified GM-CSF, which is produced primarily by tumor cells, as a selective inducer of de novo transferrin synthesis in neutrophils through the Jak/Stat5β pathway. GM-CSF neutralization or inhibition of Jak kinases curtailed neutrophil transferrin expression in vitro and in vivo as well as cancer metastasis. Thus, transferrin provides a mechanistic link between neutrophils and metastatic growth owing to the ability of tumor-infiltrating neutrophils to locally deliver this growth-promoting protein in response to GM-CSF stimulation. Our study identifies neutrophil-derived transferrin as a key regulator of metastatic tumor cell growth and a therapeutic target for antimetastatic treatment.}, } @article {pmid30301792, year = {2018}, author = {Guseman, AJ and Perez Goncalves, GM and Speer, SL and Young, GB and Pielak, GJ}, title = {Protein shape modulates crowding effects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10965-10970}, pmid = {30301792}, issn = {1091-6490}, support = {F31 GM126763/GM/NIGMS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; }, mesh = {Ficoll/chemistry ; Macromolecular Substances/chemistry ; Polyethylene Glycols/chemistry ; Polymers/chemistry ; Protein Interaction Maps/physiology ; Protein Multimerization/physiology ; Proteins/*chemistry ; }, abstract = {Protein-protein interactions are usually studied in dilute buffered solutions with macromolecule concentrations of <10 g/L. In cells, however, the macromolecule concentration can exceed 300 g/L, resulting in nonspecific interactions between macromolecules. These interactions can be divided into hard-core steric repulsions and "soft" chemical interactions. Here, we test a hypothesis from scaled particle theory; the influence of hard-core repulsions on a protein dimer depends on its shape. We tested the idea using a side-by-side dumbbell-shaped dimer and a domain-swapped ellipsoidal dimer. Both dimers are variants of the B1 domain of protein G and differ by only three residues. The results from the relatively inert synthetic polymer crowding molecules, Ficoll and PEG, support the hypothesis, indicating that the domain-swapped dimer is stabilized by hard-core repulsions while the side-by-side dimer shows little to no stabilization. We also show that protein cosolutes, which interact primarily through nonspecific chemical interactions, have the same small effect on both dimers. Our results suggest that the shape of the protein dimer determines the influence of hard-core repulsions, providing cells with a mechanism for regulating protein-protein interactions.}, } @article {pmid30301791, year = {2018}, author = {Zhang, J and Wang, N and Miao, Y and Hauser, F and McCammon, JA and Rappel, WJ and Schroeder, JI}, title = {Identification of SLAC1 anion channel residues required for CO2/bicarbonate sensing and regulation of stomatal movements.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11129-11137}, pmid = {30301791}, issn = {1091-6490}, support = {P41 GM103426/GM/NIGMS NIH HHS/United States ; R01 GM031749/GM/NIGMS NIH HHS/United States ; R01 GM060396/GM/NIGMS NIH HHS/United States ; }, mesh = {Abscisic Acid/pharmacology ; Animals ; Arabidopsis/metabolism ; Arabidopsis Proteins/*metabolism ; Bicarbonates/*metabolism ; Carbon Dioxide/*metabolism ; Cell Membrane/drug effects/metabolism ; Ion Transport/drug effects/physiology ; Membrane Proteins/*metabolism ; Mutation/drug effects/physiology ; Oocytes/drug effects/metabolism ; Plant Leaves/drug effects/metabolism ; Plant Stomata/drug effects/*metabolism ; Signal Transduction/drug effects/physiology ; Water/metabolism ; Xenopus/metabolism ; }, abstract = {Increases in CO2 concentration in plant leaves due to respiration in the dark and the continuing atmospheric [CO2] rise cause closing of stomatal pores, thus affecting plant-water relations globally. However, the underlying CO2/bicarbonate (CO2/HCO3-) sensing mechanisms remain unknown. [CO2] elevation in leaves triggers stomatal closure by anion efflux mediated via the SLAC1 anion channel localized in the plasma membrane of guard cells. Previous reconstitution analysis has suggested that intracellular bicarbonate ions might directly up-regulate SLAC1 channel activity. However, whether such a CO2/HCO3- regulation of SLAC1 is relevant for CO2 control of stomatal movements in planta remains unknown. Here, we computationally probe for candidate bicarbonate-interacting sites within the SLAC1 anion channel via long-timescale Gaussian accelerated molecular dynamics (GaMD) simulations. Mutations of two putative bicarbonate-interacting residues, R256 and R321, impaired the enhancement of the SLAC1 anion channel activity by CO2/HCO3- in Xenopus oocytes. Mutations of the neighboring charged amino acid K255 and residue R432 and the predicted gate residue F450 did not affect HCO3- regulation of SLAC1. Notably, gas-exchange experiments with slac1-transformed plants expressing mutated SLAC1 proteins revealed that the SLAC1 residue R256 is required for CO2 regulation of stomatal movements in planta, but not for abscisic acid (ABA)-induced stomatal closing. Patch clamp analyses of guard cells show that activation of S-type anion channels by CO2/HCO3-, but not by ABA, was impaired, indicating the relevance of R256 for CO2 signal transduction. Together, these analyses suggest that the SLAC1 anion channel is one of the physiologically relevant CO2/HCO3- sensors in guard cells.}, } @article {pmid30301469, year = {2018}, author = {Cadena, AM and Ma, Y and Ding, T and Bryant, M and Maiello, P and Geber, A and Lin, PL and Flynn, JL and Ghedin, E}, title = {Profiling the airway in the macaque model of tuberculosis reveals variable microbial dysbiosis and alteration of community structure.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {180}, pmid = {30301469}, issn = {2049-2618}, support = {R03 AI122067/AI/NIAID NIH HHS/United States ; T32 AI089443/AI/NIAID NIH HHS/United States ; R01 AI111871/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: The specific interactions of Mycobacterium tuberculosis (Mtb), the causative agent of tuberculosis (TB), and the lung microbiota in infection are entirely unexplored. Studies in cancer and other infectious diseases suggest that there are important exchanges occurring between host and microbiota that influence the immunological landscape. This can result in alterations in immune regulation and inflammation both locally and systemically. To assess whether Mtb infection modifies the lung microbiome, and identify changes in microbial abundance and diversity as a function of pulmonary inflammation, we compared infected and uninfected lung lobe washes collected serially from 26 macaques by bronchoalveolar lavage over the course of infection.

RESULTS: We found that Mtb induced an initial increase in lung microbial diversity at 1 month post infection that normalized by 5 months of infection across all macaques. Several core genera showed global shifts from baseline and throughout infection. Moreover, we identified several specific taxa normally associated with the oral microbiome that increased in relative abundance in the lung following Mtb infection, including SR1, Aggregatibacter, Leptotrichia, Prevotella, and Campylobacter. On an individual macaque level, we found significant heterogeneity in both the magnitude and duration of change within the lung microbial community that was unrelated to lung inflammation and lobe involvement as seen by positron emission tomography/computed tomography (PET/CT) imaging. By comparing microbial interaction networks pre- and post-infection using the predictive algorithm SPIEC-EASI, we observe that extra connections are gained by Actinomycetales, the order containing Mtb, in spite of an overall reduction in the number of interactions of the whole community post-infection, implicating Mtb-driven ecological reorganization within the lung.

CONCLUSIONS: This study is the first to probe the dynamic interplay between Mtb and host microbiota longitudinally and in the macaque lung. Our findings suggest that Mtb can alter the microbial landscape of infected lung lobes and that these interactions induce dysbiosis that can disrupt oral-airway boundaries, shift overall lung diversity, and modulate specific microbial relationships. We also provide evidence that this effect is heterogeneous across different macaques. Overall, however, the changes to the airway microbiota after Mtb infection were surprisingly modest, despite a range of Mtb-induced pulmonary inflammation in this cohort of macaques.}, } @article {pmid30301451, year = {2018}, author = {Hassan, M and Namasivayam, AA and DeBlasio, D and Fatima, N and Siranosian, B and Parra, RG and Cuypers, B and Shome, S and Monzon, AM and Fumey, J and Rahman, F}, title = {Reflections on a journey: a retrospective of the ISCB Student Council symposium series.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 12}, pages = {347}, pmid = {30301451}, issn = {1471-2105}, mesh = {*Computational Biology ; *Congresses as Topic ; Fellowships and Scholarships ; Humans ; Peer Review, Research ; Publications ; Research Support as Topic/economics ; *Students ; }, abstract = {This article describes the motivation, origin and evolution of the student symposia series organised by the ISCB Student Council. The meeting series started thirteen years ago in Madrid and has spread to four continents. The article concludes with the highlights of the most recent edition of annual Student Council Symposium held in conjunction with the 25th Conference on Intelligent Systems for Molecular Biology and the 16th European Conference on Computational Biology, in Prague, in July 2017.}, } @article {pmid30300123, year = {2018}, author = {Nouioui, I and Brunet, LR and Simpson, D and Klenk, HP and Goodfellow, M}, title = {Description of a novel species of fast growing mycobacterium: Mycobacterium kyogaense sp. nov., a scotochromogenic strain received as Mycobacterium vaccae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3726-3734}, doi = {10.1099/ijsem.0.003039}, pmid = {30300123}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Genes, Bacterial ; Mycobacterium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A polyphasic study was undertaken to determine the taxonomic status of a rapidly growing, scotochromogenic organism that had been received as Mycobacterium vaccaeNCTC 11659T. The organism was found to have chemotaxonomic and cultural properties in accord with its assignment to the genus Mycobacteriumand was distinguished from the type strain of Mycobacterium vaccaeand from other closely related reference strains on the basis of concatenated sequences of 16S rRNA, gyrB, hsp65, recA and rpoB genes. It was also distinguished from M. vaccaestrain DSM 43292T and from the type strain of Mycobacterium obuense, its nearest phylogenetic neighbour, on the basis of chemotaxonomic and phenotypic data and digital DNA -DNA relatedness values of 22.7 and 68.3 %, respectively. These datasets not only indicate that strain NCTC 11659T had been misclassified as M. vaccae but that it merits recognition as representing a novel species of the genus Mycobacterium. It is proposed that the organism be classified as Mycobacteriumkyogaense sp. nov.}, } @article {pmid30300120, year = {2018}, author = {Chen, RW and Wang, KX and Wang, FZ and He, YQ and Long, LJ and Tian, XP}, title = {Rubrobacter indicoceani sp. nov., a new marine actinobacterium isolated from Indian Ocean sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3487-3493}, doi = {10.1099/ijsem.0.003018}, pmid = {30300120}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Indian Ocean ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ultraviolet Rays ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel mesophilic marine actinobacterial strain, designated as SCSIO 08198T, was isolated from a deep-sea sediment sample collected from the Indian Ocean. The strain was Gram-stain-positive, rod-shaped and salmon pink in colour. Good growth occurred on marine agar with 1-5 % (w/v) NaCl and incubation at 28 °C for more than a fortnight. Sensitive to short ultraviolet radiation. Analysis of 16S rRNA gene sequences revealed that strain SCSIO 08198T had the highest similarity of 97.2 % to Rubrobacter radiotolerans DSM 5868T, and loosely related (<94.2 %) to all other species in the genus Rubrobacter. Phylogenetic analysis based on nearly complete 16S rRNA gene sequences revealed that the novel isolate shared a lineage with members of the genus Rubrobacter. The total cellular fatty acid profile was dominated by C16 : 0 12-methyl. MK-8 was the main menaquinone. The peptidoglycan type was A3α (l-Lys-l-Ala). The major phospholipids were diphosphatidylglycerol, phosphatidylglycerol and unidentified phospholipids. Based on the whole genome sequence analysis, the genome size is 3 078 689 bp with DNA G+C value of 63.8 mol%, including one circular chromosome and two plasmids. Based on these polyphasic data, a new species, Rubrobacterindicoceani sp. nov., is proposed, with the type strain SCSIO 08198T (=DSM 105148T=CGMCC 1.16398T).}, } @article {pmid30299474, year = {2018}, author = {Maroniche, GA and Diaz, PR and Borrajo, MP and Valverde, CF and Creus, CM}, title = {Friends or foes in the rhizosphere: traits of fluorescent Pseudomonas that hinder Azospirillum brasilense growth and root colonization.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy202}, pmid = {30299474}, issn = {1574-6941}, abstract = {Bacteria of the Azospirillum and Pseudomonas genera are ubiquitous members of the rhizosphere, where they stimulate plant growth. Given the outstanding capacity of pseudomonads to antagonize other microorganisms, we analyzed the interaction between these two bacterial groups to identify determinants of their compatibility. We could establish that, when in direct contact, certain Pseudomonas strains produce lethality on Azospirillum brasilense cells using an antibacterial type 6 secretion system. When analyzing the effect of Pseudomonas spp. diffusible metabolites on A. brasilense growth on King's B medium, we detected strong inhibitory effects, mostly mediated by siderophores. On Congo Red medium, both inhibitory and stimulatory effects were induced by unidentified compounds. Under this condition, Pseudomonas protegens CHA0 produced a Gac/Rsm-regulated antibiotic which specifically inhibited A. brasilense Sp7 but not Sp245. This effect was not associated with the production of 2,4-diacetylphloroglucinol. The three identified antagonism determinants were also active in vivo, producing a reduction of viable cells of A. brasilense in the roots of wheat seedlings when co-inoculated with pseudomonads. These results are relevant to the understanding of social dynamics in the rhizosphere and might aid in the selection of strains for mixed inoculants.}, } @article {pmid30299466, year = {2018}, author = {Ivancic, I and Paliaga, P and Pfannkuchen, M and Djakovac, T and Najdek, M and Steiner, P and Korlevic, M and Markovski, M and Baricevic, A and Tankovic, MS and Herndl, GJ}, title = {Seasonal variations in extracellular enzymatic activity in marine snow-associated microbial communities and their impact on the surrounding water.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy198}, pmid = {30299466}, issn = {1574-6941}, abstract = {Seasonal changes of microbial abundance and associated extracellular enzymatic activity in marine snow and in seawater were studied in the northern Adriatic during a three-year period. Marine snow was present during the entire period of investigation, although in higher concentrations during summer than during winter. Microorganisms densely colonized marine snow and aggregate-associated enzymatic activity was substantially higher (up to 105 times) than in seawater. Alkaline phosphatase activity (APA) and aminopeptidase activity in marine snow showed seasonal variations with higher values in late spring-summer than in autumn-winter, probably in response to changes in the quantity and quality of organic matter. The highest cell-specific bacterial activity was found for phosphatase, followed by peptidase, and the lowest was for glucosidases. Differential hydrolysis of marine snow-derived organic matter points to the well-known phosphorus limitation of the northern Adriatic and indicates preferential utilization of phosphorus- and nitrogen-rich organic compounds by microbes, while hydrolysis of polysaccharides seemed to be less important. In oligotrophic conditions during summer, organic matter released from marine snow might represent a significant source of substrate for free-living bacteria in seawater. For the first time microorganisms producing APA in marine snow were identified, revealing that dense populations of bacteria expressed APA, while cyanobacteria did not. Cyanobacteria proliferating in marine snow could benefit from phosphorus release by bacteria and nanoflagellates.}, } @article {pmid30298925, year = {2018}, author = {Singh, A and Punzalan, D}, title = {The strength of sex-specific selection in the wild.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2818-2824}, doi = {10.1111/evo.13625}, pmid = {30298925}, issn = {1558-5646}, support = {//NSERC Discovery Grant/ ; //University of Toronto Fellowship/ ; }, abstract = {Anisogamy predisposes the sexes to very different patterns of selection on shared traits. Selective differences between the sexes may manifest as changes in the direction or strength of selection acting on shared phenotypes. Although previous studies have found evidence for widespread differences in the direction of selection between the sexes, surprisingly little is known regarding potential differences in the magnitude of selection and whether such differences might be confined to specific components of fitness. We conducted a meta-analysis using 865 estimates of phenotypic selection from wild populations to characterize sex differences in the strength of selection and to ask whether different components of fitness exhibit differences in sex bias in the strength of selection. Overall, consistent with past results, we find evidence of male bias in the strength of selection, driven primarily by components of fitness related to mating success and we discuss several evolutionary implications.}, } @article {pmid30298918, year = {2018}, author = {Werry, N}, title = {Digest: The importance of genital morphology in Drosophila copulation.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2567-2568}, doi = {10.1111/evo.13621}, pmid = {30298918}, issn = {1558-5646}, abstract = {Drosophila is a common model organism in the study of reproductive isolation. In their 2018 work, Tanaka et al. used introgression to substitute D. mauritiana genomic segments into a D. simulans genetic background, creating lines with modified genital structures. These changes were found to significantly alter the copulation duration and motility of mating pairs by influencing genital coupling.}, } @article {pmid30298917, year = {2018}, author = {van Bergen, E and Lafuente, E}, title = {Digest: The guppy project: Predicting evolution in the wild.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2569-2570}, doi = {10.1111/evo.13620}, pmid = {30298917}, issn = {1558-5646}, } @article {pmid30298913, year = {2018}, author = {Bartlett, LJ and Wilfert, L and Boots, M}, title = {A genotypic trade-off between constitutive resistance to viral infection and host growth rate.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2749-2757}, doi = {10.1111/evo.13623}, pmid = {30298913}, issn = {1558-5646}, support = {NE/J009784/1//Natural Environment Research Council/ ; NE/K014617/1//Natural Environment Research Council/ ; NE/L002434/1//Natural Environment Research Council/ ; BB/L010879/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Genotypic trade-offs are fundamental to the understanding of the evolution of life-history traits. In particular, the evolution of optimal host defense and the maintenance of variation in defense against infectious disease is thought to be underpinned by such evolutionary trade-offs. However, empirical demonstrations of these trade-offs that satisfy the strict assumptions made by theoretical models are rare. Additionally, none of these trade-offs have yet been shown to be robustly replicable using a variety of different experimental approaches to rule out confounding issues with particular experimental designs. Here, we use inbred isolines as a novel experimental approach to test whether a trade-off between viral resistance and growth rate in Plodia interpunctella, previously demonstrated by multiple selection experiments, is robust and meets the strict criteria required to underpin theoretical work in this field. Critically, we demonstrate that this trade-off is both genetic and constitutive. This finding helps support the large body of theory that relies on these assumptions, and makes this trade-off for resistance unique in being replicated through multiple experimental approaches and definitively shown to be genetic and constitutive.}, } @article {pmid30298912, year = {2018}, author = {Greenspoon, PB and Spencer, HG}, title = {The evolution of epigenetically mediated adaptive transgenerational plasticity in a subdivided population.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2773-2780}, doi = {10.1111/evo.13619}, pmid = {30298912}, issn = {1558-5646}, support = {UOO1612//Marsden Fund of the Royal Society of New Zealand/ ; }, abstract = {Transgenerational plasticity (TGP) occurs when offspring exhibit plasticity in traits induced by the environments experienced by their parents, and represents a nongenetic mechanism of inheritance. Evidence that traits can be transmitted to future generations by means other than genetic inheritance has caused a surge of interest in epigenetic inheritance, but evidence for epigenetic modifications being both adaptive and heritable remains scarce. What features would make a species most prone to evolve a system of epigenetically mediated adaptive TGP? Here, we use population-genetic models modified to include epigenetic induction and inheritance to investigate if and when epigenetically mediated adaptive TGP would be expected to evolve for a population subdivided between two habitats connected by migration. We show that differences in the direction of selection between the two habitats drives the evolution of epigenetically mediated adaptive TGP. With low migration, the strength of indirect selection in favor of epigenetically mediated adaptive TGP increases with migration rate. Yet, with higher migration, the opposite trend is observed. We predict that species subdivided between habitats that differ in the direction of selection with moderate migration rates between the habitats would be most likely to evolve epigenetically mediated adaptive TGP if costs of producing such systems are not too high.}, } @article {pmid30298689, year = {2018}, author = {Terashima, M and Ohashi, K and Takasuka, TE and Kojima, H and Fukui, M}, title = {Antarctic heterotrophic bacterium Hymenobacter nivis P3T displays light-enhanced growth and expresses putative photoactive proteins.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12702}, pmid = {30298689}, issn = {1758-2229}, support = {//Institute of Fermentation, Osaka/ ; //Institute of Low Temperature Science/ ; //Hokkaido University/ ; }, abstract = {Hymenobacter nivis P3T is a heterotrophic bacterium isolated from Antarctic red snow generated by algal blooms. Despite being non-photosynthetic, H. nivis was dominantly found in the red snow environment that is exposed to high light and UV irradiation, suggesting that this species can flourish under such harsh conditions. In order to further understand the adaptive strategies on the snow surface environment of Antarctica, the genome of H. nivis P3T was sequenced and analyzed, which identified genes putatively encoding for light-reactive proteins such as proteorhodopsin, phytochrome, photolyase and several copies of cryptochromes. Culture-based experiments revealed that H. nivis P3T growth was significantly enhanced under light conditions, while dark conditions had increased extracellular polymeric substances. Furthermore, the expression of several putative light-reactive proteins was determined by proteomic analysis. These results indicate that H. nivis P3T is able to potentially utilize light, which may explain its dominance on the red snow surface environment of Antarctica. ORIGINALITY-SIGNIFICANCE STATEMENT: The role of proteorhodopsin in heterotrophic bacteria is not well-characterized, as only a handful of proteorhodopsin-harbouring isolates were shown to have a light-enhanced phenotype through culture-based experiments to date. This is the first study that demonstrates light-stimulated growth and protein expression evidence of photoactive proteins for a non-marine psychrophile and for a member of the genus Hymenobacter. It is also the first study that provides comprehensive proteome information for this genus. This study presents significant results in understanding the adaptive mechanism of a heterotrophic non-photosynthetic bacterium thriving on the snow surface environment of Antarctica as well as demonstrating the role of light-utilization in promoting growth, possibly through proteorhodopsin.}, } @article {pmid30298642, year = {2018}, author = {Humphreys, RK and Ruxton, GD}, title = {Dropping to escape: a review of an under-appreciated antipredator defence.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12466}, pmid = {30298642}, issn = {1469-185X}, abstract = {Dropping is a common antipredator defence that enables rapid escape from a perceived threat. However, despite its immediate effectiveness in predator-prey encounters (and against other dangers such as a parasitoid or an aggressive conspecific), it remains an under-appreciated defence strategy in the scientific literature. Dropping has been recorded in a wide range of taxa, from primates to lizards, but has been studied most commonly in insects. Insects have been found to utilise dropping in response to both biotic and abiotic stimuli, sometimes dependent on mechanical or chemical cues. Whatever the trigger for dropping, the decision to drop by prey will present a range of inter-related costs and benefits to the individual and so there will be subtle complexities in the trade-offs surrounding this defensive behaviour. In predatory encounters, dropping by prey will also impose varying costs and benefits on the predator - or predators - involved in the system. There may be important trade-offs involved in the decision made by predators regarding whether to pursue prey or not, but the predator perspective on dropping has been less explored at present. Beyond its function as an escape tactic, dropping has also been suggested to be an important precursor to flight in insects and further study could greatly improve understanding of its evolutionary importance. Dropping in insects could also prove of significant practical importance if an improved understanding can be applied to integrated pest-management strategies. Currently the non-consumptive effects of predators on their prey are under-appreciated in biological control and it may be that the dropping behaviour of many pest species could be exploited via management practices to improve crop protection. Overall, this review aims to provide a comprehensive synthesis of the current literature on dropping and to raise awareness of this fascinating and widespread behaviour. It also seeks to offer some novel hypotheses and highlight key avenues for future research.}, } @article {pmid30298597, year = {2018}, author = {D'Arrigo, I and Cardoso, JGR and Rennig, M and Sonnenschein, N and Herrgård, MJ and Long, KS}, title = {Analysis of Pseudomonas putida growth on non-trivial carbon sources using transcriptomics and genome-scale modelling.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12704}, pmid = {30298597}, issn = {1758-2229}, support = {317058//Novo Nordisk Foundation Center for Biosustainability/ ; 317058//European Union Seventh Framework Programme/ ; }, abstract = {Pseudomonas putida is characterized by a versatile metabolism and stress tolerance traits that allow the bacterium to cope with different environmental conditions. In this work, the mechanisms that allow P. putida KT2440 to grow in the presence of four sole carbon sources (glucose, citrate, ferulic acid, serine) were investigated by RNA sequencing (RNA-seq) and genome-scale metabolic modelling. Transcriptomic data identified uptake systems for the four carbon sources, and candidates were subjected to preliminary experimental characterization by mutant strain growth to test their involvement in substrate assimilation. The OpdH and BenF-like porins were involved in citrate and ferulic acid uptake respectively. The citrate transporter (encoded by PP_0147) and the TctABC system were important for supporting cell growth in citrate; PcaT and VanK were associated with ferulic acid uptake; and the ABC transporter AapJPQM was involved in serine transport. A genome-scale metabolic model of P. putida KT2440 was used to integrate and analyze the transcriptomic data, identifying and confirming the active catabolic pathways for each carbon source. This study reveals novel information about transporters that are essential for understanding bacterial adaptation to different environments.}, } @article {pmid30298570, year = {2019}, author = {Roux, S and Brum, JR}, title = {A viral reckoning: viruses emerge as essential manipulators of global ecosystems.}, journal = {Environmental microbiology reports}, volume = {11}, number = {1}, pages = {3-8}, doi = {10.1111/1758-2229.12700}, pmid = {30298570}, issn = {1758-2229}, support = {DE-AC02-05CH11231//U.S. Department of Energy/ ; //Lawrence Berkeley National Laboratory/ ; //Laboratory Directed Research and Development/ ; //Office of Science/ ; }, } @article {pmid30297971, year = {2018}, author = {Zhang, J and Zhang, X and Tang, H and Zhang, Q and Hua, X and Ma, X and Zhu, F and Jones, T and Zhu, X and Bowers, J and Wai, CM and Zheng, C and Shi, Y and Chen, S and Xu, X and Yue, J and Nelson, DR and Huang, L and Li, Z and Xu, H and Zhou, D and Wang, Y and Hu, W and Lin, J and Deng, Y and Pandey, N and Mancini, M and Zerpa, D and Nguyen, JK and Wang, L and Yu, L and Xin, Y and Ge, L and Arro, J and Han, JO and Chakrabarty, S and Pushko, M and Zhang, W and Ma, Y and Ma, P and Lv, M and Chen, F and Zheng, G and Xu, J and Yang, Z and Deng, F and Chen, X and Liao, Z and Zhang, X and Lin, Z and Lin, H and Yan, H and Kuang, Z and Zhong, W and Liang, P and Wang, G and Yuan, Y and Shi, J and Hou, J and Lin, J and Jin, J and Cao, P and Shen, Q and Jiang, Q and Zhou, P and Ma, Y and Zhang, X and Xu, R and Liu, J and Zhou, Y and Jia, H and Ma, Q and Qi, R and Zhang, Z and Fang, J and Fang, H and Song, J and Wang, M and Dong, G and Wang, G and Chen, Z and Ma, T and Liu, H and Dhungana, SR and Huss, SE and Yang, X and Sharma, A and Trujillo, JH and Martinez, MC and Hudson, M and Riascos, JJ and Schuler, M and Chen, LQ and Braun, DM and Li, L and Yu, Q and Wang, J and Wang, K and Schatz, MC and Heckerman, D and Van Sluys, MA and Souza, GM and Moore, PH and Sankoff, D and VanBuren, R and Paterson, AH and Nagai, C and Ming, R}, title = {Allele-defined genome of the autopolyploid sugarcane Saccharum spontaneum L.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1565-1573}, doi = {10.1038/s41588-018-0237-2}, pmid = {30297971}, issn = {1546-1718}, abstract = {Modern sugarcanes are polyploid interspecific hybrids, combining high sugar content from Saccharum officinarum with hardiness, disease resistance and ratooning of Saccharum spontaneum. Sequencing of a haploid S. spontaneum, AP85-441, facilitated the assembly of 32 pseudo-chromosomes comprising 8 homologous groups of 4 members each, bearing 35,525 genes with alleles defined. The reduction of basic chromosome number from 10 to 8 in S. spontaneum was caused by fissions of 2 ancestral chromosomes followed by translocations to 4 chromosomes. Surprisingly, 80% of nucleotide binding site-encoding genes associated with disease resistance are located in 4 rearranged chromosomes and 51% of those in rearranged regions. Resequencing of 64 S. spontaneum genomes identified balancing selection in rearranged regions, maintaining their diversity. Introgressed S. spontaneum chromosomes in modern sugarcanes are randomly distributed in AP85-441 genome, indicating random recombination among homologs in different S. spontaneum accessions. The allele-defined Saccharum genome offers new knowledge and resources to accelerate sugarcane improvement.}, } @article {pmid30297970, year = {2018}, author = {Cousminer, DL and Grant, SFA}, title = {Public resources aid diabetes gene discovery.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1499-1500}, doi = {10.1038/s41588-018-0242-5}, pmid = {30297970}, issn = {1546-1718}, } @article {pmid30297969, year = {2018}, author = {Mahajan, A and Taliun, D and Thurner, M and Robertson, NR and Torres, JM and Rayner, NW and Payne, AJ and Steinthorsdottir, V and Scott, RA and Grarup, N and Cook, JP and Schmidt, EM and Wuttke, M and Sarnowski, C and Mägi, R and Nano, J and Gieger, C and Trompet, S and Lecoeur, C and Preuss, MH and Prins, BP and Guo, X and Bielak, LF and Below, JE and Bowden, DW and Chambers, JC and Kim, YJ and Ng, MCY and Petty, LE and Sim, X and Zhang, W and Bennett, AJ and Bork-Jensen, J and Brummett, CM and Canouil, M and Ec Kardt, KU and Fischer, K and Kardia, SLR and Kronenberg, F and Läll, K and Liu, CT and Locke, AE and Luan, J and Ntalla, I and Nylander, V and Schönherr, S and Schurmann, C and Yengo, L and Bottinger, EP and Brandslund, I and Christensen, C and Dedoussis, G and Florez, JC and Ford, I and Franco, OH and Frayling, TM and Giedraitis, V and Hackinger, S and Hattersley, AT and Herder, C and Ikram, MA and Ingelsson, M and Jørgensen, ME and Jørgensen, T and Kriebel, J and Kuusisto, J and Ligthart, S and Lindgren, CM and Linneberg, A and Lyssenko, V and Mamakou, V and Meitinger, T and Mohlke, KL and Morris, AD and Nadkarni, G and Pankow, JS and Peters, A and Sattar, N and Stančáková, A and Strauch, K and Taylor, KD and Thorand, B and Thorleifsson, G and Thorsteinsdottir, U and Tuomilehto, J and Witte, DR and Dupuis, J and Peyser, PA and Zeggini, E and Loos, RJF and Froguel, P and Ingelsson, E and Lind, L and Groop, L and Laakso, M and Collins, FS and Jukema, JW and Palmer, CNA and Grallert, H and Metspalu, A and Dehghan, A and Köttgen, A and Abecasis, GR and Meigs, JB and Rotter, JI and Marchini, J and Pedersen, O and Hansen, T and Langenberg, C and Wareham, NJ and Stefansson, K and Gloyn, AL and Morris, AP and Boehnke, M and McCarthy, MI}, title = {Fine-mapping type 2 diabetes loci to single-variant resolution using high-density imputation and islet-specific epigenome maps.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1505-1513}, pmid = {30297969}, issn = {1546-1718}, support = {R01 DK078616/DK/NIDDK NIH HHS/United States ; MC_UU_12015/1//Medical Research Council/United Kingdom ; K24 DK080140/DK/NIDDK NIH HHS/United States ; U01 DK078616/DK/NIDDK NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; 098381//Wellcome Trust/United Kingdom ; }, abstract = {We expanded GWAS discovery for type 2 diabetes (T2D) by combining data from 898,130 European-descent individuals (9% cases), after imputation to high-density reference panels. With these data, we (i) extend the inventory of T2D-risk variants (243 loci, 135 newly implicated in T2D predisposition, comprising 403 distinct association signals); (ii) enrich discovery of lower-frequency risk alleles (80 index variants with minor allele frequency <5%, 14 with estimated allelic odds ratio >2); (iii) substantially improve fine-mapping of causal variants (at 51 signals, one variant accounted for >80% posterior probability of association (PPA)); (iv) extend fine-mapping through integration of tissue-specific epigenomic information (islet regulatory annotations extend the number of variants with PPA >80% to 73); (v) highlight validated therapeutic targets (18 genes with associations attributable to coding variants); and (vi) demonstrate enhanced potential for clinical translation (genome-wide chip heritability explains 18% of T2D risk; individuals in the extremes of a T2D polygenic risk score differ more than ninefold in prevalence).}, } @article {pmid30297968, year = {2018}, author = {Raj, T and Li, YI and Wong, G and Humphrey, J and Wang, M and Ramdhani, S and Wang, YC and Ng, B and Gupta, I and Haroutunian, V and Schadt, EE and Young-Pearse, T and Mostafavi, S and Zhang, B and Sklar, P and Bennett, DA and De Jager, PL}, title = {Integrative transcriptome analyses of the aging brain implicate altered splicing in Alzheimer's disease susceptibility.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1584-1592}, doi = {10.1038/s41588-018-0238-1}, pmid = {30297968}, issn = {1546-1718}, support = {U01 AG046152/AG/NIA NIH HHS/United States ; R01 AG054005/AG/NIA NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; P50 MH084053/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; P01 AG002219/AG/NIA NIH HHS/United States ; R01 MH093725/MH/NIMH NIH HHS/United States ; P50 AG005138/AG/NIA NIH HHS/United States ; HHSN271201300031C/MH/NIMH NIH HHS/United States ; P50 MH066392/MH/NIMH NIH HHS/United States ; R01 MH080405/MH/NIMH NIH HHS/United States ; R01 AG036836/AG/NIA NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; R01 AG015819/AG/NIA NIH HHS/United States ; }, abstract = {Here we use deep sequencing to identify sources of variation in mRNA splicing in the dorsolateral prefrontal cortex (DLPFC) of 450 subjects from two aging cohorts. Hundreds of aberrant pre-mRNA splicing events are reproducibly associated with Alzheimer's disease. We also generate a catalog of splicing quantitative trait loci (sQTL) effects: splicing of 3,006 genes is influenced by genetic variation. We report that altered splicing is the mechanism for the effects of the PICALM, CLU and PTK2B susceptibility alleles. Furthermore, we performed a transcriptome-wide association study and identified 21 genes with significant associations with Alzheimer's disease, many of which are found in known loci, whereas 8 are in novel loci. These results highlight the convergence of old and new genes associated with Alzheimer's disease in autophagy-lysosomal-related pathways. Overall, this study of the transcriptome of the aging brain provides evidence that dysregulation of mRNA splicing is a feature of Alzheimer's disease and is, in some cases, genetically driven.}, } @article {pmid30297967, year = {2018}, author = {Weiss, CV and Roop, JI and Hackley, RK and Chuong, JN and Grigoriev, IV and Arkin, AP and Skerker, JM and Brem, RB}, title = {Genetic dissection of interspecific differences in yeast thermotolerance.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1501-1504}, doi = {10.1038/s41588-018-0243-4}, pmid = {30297967}, issn = {1546-1718}, abstract = {Some of the most unique and compelling survival strategies in the natural world are fixed in isolated species1. To date, molecular insight into these ancient adaptations has been limited, as classic experimental genetics has focused on interfertile individuals in populations2. Here we use a new mapping approach, which screens mutants in a sterile interspecific hybrid, to identify eight housekeeping genes that underlie the growth advantage of Saccharomyces cerevisiae over its distant relative Saccharomyces paradoxus at high temperature. Pro-thermotolerance alleles at these mapped loci were required for the adaptive trait in S. cerevisiae and sufficient for its partial reconstruction in S. paradoxus. The emerging picture is one in which S. cerevisiae improved the heat resistance of multiple components of the fundamental growth machinery in response to selective pressure. Our study lays the groundwork for the mapping of genotype to phenotype in clades of sister species across Eukarya.}, } @article {pmid30297966, year = {2018}, author = {Gazal, S and Loh, PR and Finucane, HK and Ganna, A and Schoech, A and Sunyaev, S and Price, AL}, title = {Functional architecture of low-frequency variants highlights strength of negative selection across coding and non-coding annotations.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1600-1607}, pmid = {30297966}, issn = {1546-1718}, support = {U01 HG009379/HG/NHGRI NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; R01 MH101244/MH/NIMH NIH HHS/United States ; U01 HG009088/HG/NHGRI NIH HHS/United States ; R01 MH109978/MH/NIMH NIH HHS/United States ; }, abstract = {Common variant heritability has been widely reported to be concentrated in variants within cell-type-specific non-coding functional annotations, but little is known about low-frequency variant functional architectures. We partitioned the heritability of both low-frequency (0.5%≤ minor allele frequency <5%) and common (minor allele frequency ≥5%) variants in 40 UK Biobank traits across a broad set of functional annotations. We determined that non-synonymous coding variants explain 17 ± 1% of low-frequency variant heritability ([Formula: see text]) versus 2.1 ± 0.2% of common variant heritability ([Formula: see text]). Cell-type-specific non-coding annotations that were significantly enriched for [Formula: see text] of corresponding traits were similarly enriched for [Formula: see text] for most traits, but more enriched for brain-related annotations and traits. For example, H3K4me3 marks in brain dorsolateral prefrontal cortex explain 57 ± 12% of [Formula: see text] versus 12 ± 2% of [Formula: see text] for neuroticism. Forward simulations confirmed that low-frequency variant enrichment depends on the mean selection coefficient of causal variants in the annotation, and can be used to predict effect size variance of causal rare variants (minor allele frequency <0.5%).}, } @article {pmid30297873, year = {2018}, author = {Bertagnolli, AD and Stewart, FJ}, title = {Author Correction: Microbial niches in marine oxygen minimum zones.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {774}, doi = {10.1038/s41579-018-0103-3}, pmid = {30297873}, issn = {1740-1534}, abstract = {In Figure 3, 'Candidatus Scalindua' and Thaumarchaeota were erroneously shown to produce nitrous oxide (N2O). As neither group directly produces N2O, the arrows and products have been removed both online and in the pdf. The authors apologize for any confusion caused.}, } @article {pmid30297801, year = {2018}, author = {Biehs, B and Dijkgraaf, GJP and Piskol, R and Alicke, B and Boumahdi, S and Peale, F and Gould, SE and de Sauvage, FJ}, title = {A cell identity switch allows residual BCC to survive Hedgehog pathway inhibition.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {429-433}, doi = {10.1038/s41586-018-0596-y}, pmid = {30297801}, issn = {1476-4687}, abstract = {Despite the efficacy of Hedgehog pathway inhibitors in the treatment of basal cell carcinoma (BCC)1, residual disease persists in some patients and may contribute to relapse when treatment is discontinued2. Here, to study the effect of the Smoothened inhibitor vismodegib on tumour clearance, we have used a Ptch1-Trp53 mouse model of BCC3 and found that mice treated with vismodegib harbour quiescent residual tumours that regrow upon cessation of treatment. Profiling experiments revealed that residual BCCs initiate a transcriptional program that closely resembles that of stem cells of the interfollicular epidermis and isthmus, whereas untreated BCCs are more similar to the hair follicle bulge. This cell identity switch was enabled by a mostly permissive chromatin state accompanied by rapid Wnt pathway activation and reprogramming of super enhancers to drive activation of key transcription factors involved in cellular identity. Accordingly, treatment of BCC with both vismodegib and a Wnt pathway inhibitor reduced the residual tumour burden and enhanced differentiation. Our study identifies a resistance mechanism in which tumour cells evade treatment by adopting an alternative identity that does not rely on the original oncogenic driver for survival.}, } @article {pmid30297800, year = {2018}, author = {Klembt, S and Harder, TH and Egorov, OA and Winkler, K and Ge, R and Bandres, MA and Emmerling, M and Worschech, L and Liew, TCH and Segev, M and Schneider, C and Höfling, S}, title = {Exciton-polariton topological insulator.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {552-556}, doi = {10.1038/s41586-018-0601-5}, pmid = {30297800}, issn = {1476-4687}, abstract = {Topological insulators-materials that are insulating in the bulk but allow electrons to flow on their surface-are striking examples of materials in which topological invariants are manifested in robustness against perturbations such as defects and disorder1. Their most prominent feature is the emergence of edge states at the boundary between areas with different topological properties. The observable physical effect is unidirectional robust transport of these edge states. Topological insulators were originally observed in the integer quantum Hall effect2 (in which conductance is quantized in a strong magnetic field) and subsequently suggested3-5 and observed6 to exist without a magnetic field, by virtue of other effects such as strong spin-orbit interaction. These were systems of correlated electrons. During the past decade, the concepts of topological physics have been introduced into other fields, including microwaves7,8, photonic systems9,10, cold atoms11,12, acoustics13,14 and even mechanics15. Recently, topological insulators were suggested to be possible in exciton-polariton systems16-18 organized as honeycomb (graphene-like) lattices, under the influence of a magnetic field. Exciton-polaritons are part-light, part-matter quasiparticles that emerge from strong coupling of quantum-well excitons and cavity photons19. Accordingly, the predicted topological effects differ from all those demonstrated thus far. Here we demonstrate experimentally an exciton-polariton topological insulator. Our lattice of coupled semiconductor microcavities is excited non-resonantly by a laser, and an applied magnetic field leads to the unidirectional flow of a polariton wavepacket around the edge of the array. This chiral edge mode is populated by a polariton condensation mechanism. We use scanning imaging techniques in real space and Fourier space to measure photoluminescence and thus visualize the mode as it propagates. We demonstrate that the topological edge mode goes around defects, and that its propagation direction can be reversed by inverting the applied magnetic field. Our exciton-polariton topological insulator paves the way for topological phenomena that involve light-matter interaction, amplification and the interaction of exciton-polaritons as a nonlinear many-body system.}, } @article {pmid30297799, year = {2018}, author = {Sánchez-Danés, A and Larsimont, JC and Liagre, M and Muñoz-Couselo, E and Lapouge, G and Brisebarre, A and Dubois, C and Suppa, M and Sukumaran, V and Del Marmol, V and Tabernero, J and Blanpain, C}, title = {A slow-cycling LGR5 tumour population mediates basal cell carcinoma relapse after therapy.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {434-438}, doi = {10.1038/s41586-018-0603-3}, pmid = {30297799}, issn = {1476-4687}, abstract = {Basal cell carcinoma (BCC) is the most frequent cancer in humans and results from constitutive activation of the Hedgehog pathway1. Several Smoothened inhibitors are used to treat Hedgehog-mediated malignancies, including BCC and medulloblastoma2. Vismodegib, a Smoothened inhibitor, leads to BCC shrinkage in the majority of patients with BCC3, but the mechanism by which it mediates BCC regression is unknown. Here we used two genetically engineered mouse models of BCC4 to investigate the mechanisms by which inhibition of Smoothened mediates tumour regression. We found that vismodegib mediates BCC regression by inhibiting a hair follicle-like fate and promoting the differentiation of tumour cells. However, a small population of tumour cells persists and is responsible for tumour relapse following treatment discontinuation, mimicking the situation found in humans5. In both mouse and human BCC, this persisting, slow-cycling tumour population expresses LGR5 and is characterized by active Wnt signalling. Combining Lgr5 lineage ablation or inhibition of Wnt signalling with vismodegib treatment leads to eradication of BCC. Our results show that vismodegib induces tumour regression by promoting tumour differentiation, and demonstrates that the synergy between Wnt and Smoothened inhibitors is a clinically relevant strategy for overcoming tumour relapse in BCC.}, } @article {pmid30297798, year = {2018}, author = {Stern, B and Ji, X and Okawachi, Y and Gaeta, AL and Lipson, M}, title = {Battery-operated integrated frequency comb generator.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {401-405}, doi = {10.1038/s41586-018-0598-9}, pmid = {30297798}, issn = {1476-4687}, abstract = {Optical frequency combs are broadband sources that offer mutually coherent, equidistant spectral lines with unprecedented precision in frequency and timing for an array of applications1. Frequency combs generated in microresonators through the Kerr nonlinearity require a single-frequency pump laser and have the potential to provide highly compact, scalable and power-efficient devices2,3. Here we demonstrate a device-a laser-integrated Kerr frequency comb generator-that fulfils this potential through use of extremely low-loss silicon nitride waveguides that form both the microresonator and an integrated laser cavity. Our device generates low-noise soliton-mode-locked combs with a repetition rate of 194 gigahertz at wavelengths near 1,550 nanometres using only 98 milliwatts of electrical pump power. The dual-cavity configuration that we use combines the laser and microresonator, demonstrating the flexibility afforded by close integration of these components, and together with the ultra low power consumption should enable production of highly portable and robust frequency and timing references, sensors and signal sources. This chip-based integration of microresonators and lasers should also provide tools with which to investigate the dynamics of comb and soliton generation.}, } @article {pmid30297749, year = {2018}, author = {Gutiérrez-Preciado, A and Saghaï, A and Moreira, D and Zivanovic, Y and Deschamps, P and López-García, P}, title = {Functional shifts in microbial mats recapitulate early Earth metabolic transitions.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1700-1708}, pmid = {30297749}, issn = {2397-334X}, abstract = {Phototrophic microbial mats dominated terrestrial ecosystems for billions of years, largely causing, through cyanobacterial oxygenic photosynthesis, but also undergoing, the Great Oxidation Event approximately 2.5 billion years ago. Taking a space-for-time approach based on the universality of core metabolic pathways expressed at ecosystem level, we studied gene content and co-occurrence networks in high-diversity metagenomes from spatially close microbial mats along a steep redox gradient. The observed functional shifts suggest that anoxygenic photosynthesis was present but not predominant under early Precambrian conditions, being accompanied by other autotrophic processes. Our data also suggest that, in contrast to general assumptions, anoxygenic photosynthesis largely expanded in parallel with the subsequent evolution of oxygenic photosynthesis and aerobic respiration. Finally, our observations might represent space-for-time evidence that the Wood-Ljungdahl carbon fixation pathway dominated phototrophic mats in early ecosystems, whereas the Calvin cycle probably evolved from pre-existing variants before becoming the dominant contemporary form of carbon fixation.}, } @article {pmid30297748, year = {2018}, author = {Bloch, NI and Corral-López, A and Buechel, SD and Kotrschal, A and Kolm, N and Mank, JE}, title = {Early neurogenomic response associated with variation in guppy female mate preference.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1772-1781}, doi = {10.1038/s41559-018-0682-4}, pmid = {30297748}, issn = {2397-334X}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Understanding the evolution of mate choice requires dissecting the mechanisms of female preference, particularly how these differ among social contexts and preference phenotypes. Here, we studied the female neurogenomic response after only 10 min of mate exposure in both a sensory component (optic tectum) and a decision-making component (telencephalon) of the brain. By comparing the transcriptional response between females with and without preferences for colourful males, we identified unique neurogenomic elements associated with the female preference phenotype that are not present in females without preference. A network analysis revealed different properties for this response at the sensory-processing and the decision-making levels, and we show that this response is highly centralized in the telencephalon. Furthermore, we identified an additional set of genes that vary in expression across social contexts, beyond mate evaluation. We show that transcription factors among these loci are predicted to regulate the transcriptional response of the genes we found to be associated with female preference.}, } @article {pmid30297747, year = {2018}, author = {Chang, SL and Wang, HK and Tung, L and Chang, TH}, title = {Adaptive transcription-splicing resynchronization upon losing an essential splicing factor.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1818-1823}, doi = {10.1038/s41559-018-0684-2}, pmid = {30297747}, issn = {2397-334X}, abstract = {Essential genes form the core of a genome and are therefore thought to be indispensable for cellular viability. However, recent findings have challenged this notion in that cells may survive in the absence of some essential genes provided that relevant genetic modifiers are in existence. We therefore hypothesized that the loss of an essential gene may not always be fatefully detrimental; instead, it may pave the way towards genome evolution. We experimentally tested this hypothesis in the context of pre-messenger RNA splicing by evolving yeast cells harbouring a permanent loss of the essential splicing factor Prp28 in the presence of a genetic modifier. Here, we show that cellular fitness can be restored by compensatory mutations that alter either the splicing machinery per se or the Spt-Ada-Gcn5 acetyltransferase transcription co-activator complex in the cells with no Prp28. Biochemical and genetic analysis revealed that slowing down transcription compensates for splicing deficiency, which in turn boosts cellular fitness. In addition, we found that inefficient splicing also conversely decreases nascent RNA production. Taken together, our data suggest that transcription-splicing synchronization contributes to robustness in the gene-expression pathway and argue that the intrinsic interconnectivity within a biological system can be exploited for compensatory evolution and system re-optimization.}, } @article {pmid30297746, year = {2018}, author = {Brown, JH and Dennhardt, AJ}, title = {Brian Maurer (1954-2018).}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1684}, doi = {10.1038/s41559-018-0700-6}, pmid = {30297746}, issn = {2397-334X}, } @article {pmid30297745, year = {2018}, author = {Hara, Y and Yamaguchi, K and Onimaru, K and Kadota, M and Koyanagi, M and Keeley, SD and Tatsumi, K and Tanaka, K and Motone, F and Kageyama, Y and Nozu, R and Adachi, N and Nishimura, O and Nakagawa, R and Tanegashima, C and Kiyatake, I and Matsumoto, R and Murakumo, K and Nishida, K and Terakita, A and Kuratani, S and Sato, K and Hyodo, S and Kuraku, S}, title = {Shark genomes provide insights into elasmobranch evolution and the origin of vertebrates.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1761-1771}, doi = {10.1038/s41559-018-0673-5}, pmid = {30297745}, issn = {2397-334X}, abstract = {Modern cartilaginous fishes are divided into elasmobranchs (sharks, rays and skates) and chimaeras, and the lack of established whole-genome sequences for the former has prevented our understanding of early vertebrate evolution and the unique phenotypes of elasmobranchs. Here we present de novo whole-genome assemblies of brownbanded bamboo shark and cloudy catshark and an improved assembly of the whale shark genome. These relatively large genomes (3.8-6.7 Gbp) contain sparse distributions of coding genes and regulatory elements and exhibit reduced molecular evolutionary rates. Our thorough genome annotation revealed Hox C genes previously hypothesized to have been lost, as well as distinct gene repertories of opsins and olfactory receptors that would be associated with adaptation to unique underwater niches. We also show the early establishment of the genetic machinery governing mammalian homoeostasis and reproduction at the jawed vertebrate ancestor. This study, supported by genomic, transcriptomic and epigenomic resources, provides a foundation for the comprehensive, molecular exploration of phenotypes unique to sharks and insights into the evolutionary origins of vertebrates.}, } @article {pmid30297744, year = {2018}, author = {Ke, PJ and Letten, AD}, title = {Coexistence theory and the frequency-dependence of priority effects.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1691-1695}, doi = {10.1038/s41559-018-0679-z}, pmid = {30297744}, issn = {2397-334X}, abstract = {Priority effects are commonly used to describe a broad suite of phenomena capturing the influence of species arrival order on the diversity, composition and function of ecological communities. Several studies have suggested reframing priority effects around the stabilizing and equalizing concepts of coexistence theory. We show that the only compatible priority effects are those characterized by positive frequency-dependence, irrespective of whether they emerge in equilibrium or non-equilibrium systems.}, } @article {pmid30297742, year = {2018}, author = {Ahrendt, SR and Quandt, CA and Ciobanu, D and Clum, A and Salamov, A and Andreopoulos, B and Cheng, JF and Woyke, T and Pelin, A and Henrissat, B and Reynolds, NK and Benny, GL and Smith, ME and James, TY and Grigoriev, IV}, title = {Leveraging single-cell genomics to expand the fungal tree of life.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1417-1428}, doi = {10.1038/s41564-018-0261-0}, pmid = {30297742}, issn = {2058-5276}, abstract = {Environmental DNA surveys reveal that most fungal diversity represents uncultured species. We sequenced the genomes of eight uncultured species across the fungal tree of life using a new single-cell genomics pipeline. We show that, despite a large variation in genome and gene space recovery from each single amplified genome (SAG), ≥90% can be recovered by combining multiple SAGs. SAGs provide robust placement for early-diverging lineages and infer a diploid ancestor of fungi. Early-diverging fungi share metabolic deficiencies and show unique gene expansions correlated with parasitism and unculturability. Single-cell genomics holds great promise in exploring fungal diversity, life cycles and metabolic potential.}, } @article {pmid30297741, year = {2018}, author = {Dragoš, A and Martin, M and Falcón García, C and Kricks, L and Pausch, P and Heimerl, T and Bálint, B and Maróti, G and Bange, G and López, D and Lieleg, O and Kovács, ÁT}, title = {Collapse of genetic division of labour and evolution of autonomy in pellicle biofilms.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1451-1460}, doi = {10.1038/s41564-018-0263-y}, pmid = {30297741}, issn = {2058-5276}, abstract = {Closely related microorganisms often cooperate, but the prevalence and stability of cooperation between different genotypes remain debatable. Here, we track the evolution of pellicle biofilms formed through genetic division of labour and ask whether partially deficient partners can evolve autonomy. Pellicles of Bacillus subtilis rely on an extracellular matrix composed of exopolysaccharide (EPS) and the fibre protein TasA. In monocultures, ∆eps and ∆tasA mutants fail to form pellicles, but, facilitated by cooperation, they succeed in co-culture. Interestingly, cooperation collapses on an evolutionary timescale and ∆tasA gradually outcompetes its partner ∆eps. Pellicle formation can evolve independently from division of labour in ∆eps and ∆tasA monocultures, by selection acting on the residual matrix component, TasA or EPS, respectively. Using a set of interdisciplinary tools, we unravel that the TasA producer (∆eps) evolves via an unconventional but reproducible substitution in TasA that modulates the biochemical properties of the protein. Conversely, the EPS producer (ΔtasA) undergoes genetically variable adaptations, all leading to enhanced EPS secretion and biofilms with different biomechanical properties. Finally, we revisit the collapse of division of labour between Δeps and ΔtasA in light of a strong frequency versus exploitability trade-off that manifested in the solitarily evolving partners. We propose that such trade-off differences may represent an additional barrier to evolution of division of labour between genetically distinct microorganisms.}, } @article {pmid30297740, year = {2018}, author = {Yurkovetskiy, L and Guney, MH and Kim, K and Goh, SL and McCauley, S and Dauphin, A and Diehl, WE and Luban, J}, title = {Primate immunodeficiency virus proteins Vpx and Vpr counteract transcriptional repression of proviruses by the HUSH complex.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1354-1361}, pmid = {30297740}, issn = {2058-5276}, support = {DP1 DA034990/DA/NIDA NIH HHS/United States ; R01 AI111809/AI/NIAID NIH HHS/United States ; R01 AI117839/AI/NIAID NIH HHS/United States ; }, abstract = {Host factors that silence provirus transcription in CD4+ memory T cells help HIV-1 escape eradication by the host immune system and by antiviral drugs1. These same factors, however, must be overcome for HIV-1 to propagate. Here we show that Vpx and Vpr encoded by diverse primate immunodeficiency viruses activate provirus transcription. Vpx and Vpr are adaptor proteins for the DCAF1-CUL4A/B E3 ubiquitin ligase that degrade SAMHD1 and increase reverse transcription2-4. Nonetheless, Vpx and Vpr have effects on reporter gene expression that are not explained by SAMHD1 degradation5-8. A screen for factors that mimic these effects identified the human silencing hub (HUSH) complex, FAM208A (TASOR/RAP140), MPHOSPH8 (MPP8), PPHLN1 (PERIPHILIN) and MORC29-13. Vpx associated with the HUSH complex and decreased steady-state level of these proteins in a DCAF1/CUL4A/B/proteasome-dependent manner14,15. Replication kinetics of HIV-1 and SIVMAC was accelerated to a similar extent by vpx or FAM208A knockdown. Finally, vpx increased steady-state levels of LINE-1 ORF1p, as previously described for FAM208A disruption11. These results demonstrate that the HUSH complex represses primate immunodeficiency virus transcription, and that, to counteract this restriction, viral Vpx or Vpr proteins degrade the HUSH complex.}, } @article {pmid30297738, year = {2018}, author = {Levchenko, I and Keidar, M and Cantrell, J and Wu, YL and Kuninaka, H and Bazaka, K and Xu, S}, title = {Explore space using swarms of tiny satellites.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {185-187}, doi = {10.1038/d41586-018-06957-2}, pmid = {30297738}, issn = {1476-4687}, } @article {pmid30297737, year = {2018}, author = {Eisenstein, M}, title = {The clinical code-breakers.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {291-293}, doi = {10.1038/d41586-018-06958-1}, pmid = {30297737}, issn = {1476-4687}, } @article {pmid30297482, year = {2018}, author = {Craske, MG and Hermans, D and Vervliet, B}, title = {Correction to 'State-of-the-art and future directions for extinction as a translational model for fear and anxiety'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, doi = {10.1098/rstb.2018.0432}, pmid = {30297482}, issn = {1471-2970}, } @article {pmid30297481, year = {2018}, author = {Fontes, CG and Dawson, TE and Jardine, K and McDowell, N and Gimenez, BO and Anderegg, L and Negrón-Juárez, R and Higuchi, N and Fine, PVA and Araújo, AC and Chambers, JQ}, title = {Dry and hot: the hydraulic consequences of a climate change-type drought for Amazonian trees.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297481}, issn = {1471-2970}, abstract = {How plants respond physiologically to leaf warming and low water availability may determine how they will perform under future climate change. In 2015-2016, an unprecedented drought occurred across Amazonia with record-breaking high temperatures and low soil moisture, offering a unique opportunity to evaluate the performances of Amazonian trees to a severe climatic event. We quantified the responses of leaf water potential, sap velocity, whole-tree hydraulic conductance (Kwt), turgor loss and xylem embolism, during and after the 2015-2016 El Niño for five canopy-tree species. Leaf/xylem safety margins (SMs), sap velocity and Kwt showed a sharp drop during warm periods. SMs were negatively correlated with vapour pressure deficit, but had no significant relationship with soil water storage. Based on our calculations of canopy stomatal and xylem resistances, the decrease in sap velocity and Kwt was due to a combination of xylem cavitation and stomatal closure. Our results suggest that warm droughts greatly amplify the degree of trees' physiological stress and can lead to mortality. Given the extreme nature of the 2015-2016 El Niño and that temperatures are predicted to increase, this work can serve as a case study of the possible impact climate warming can have on tropical trees.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297480, year = {2018}, author = {Shenkin, A and Bolker, B and Peña-Claros, M and Licona, JC and Ascarrunz, N and Putz, FE}, title = {Interactive effects of tree size, crown exposure and logging on drought-induced mortality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297480}, issn = {1471-2970}, abstract = {Large trees in the tropics are reportedly more vulnerable to droughts than their smaller neighbours. This pattern is of interest due to what it portends for forest structure, timber production, carbon sequestration and multiple other values given that intensified El Niño Southern Oscillation (ENSO) events are expected to increase the frequency and intensity of droughts in the Amazon region. What remains unclear is what characteristics of large trees render them especially vulnerable to drought-induced mortality and how this vulnerability changes with forest degradation. Using a large-scale, long-term silvicultural experiment in a transitional Amazonian forest in Bolivia, we disentangle the effects of stem diameter, tree height, crown exposure and logging-induced degradation on risks of drought-induced mortality during the 2004/2005 ENSO event. Overall, tree mortality increased in response to drought in both logged and unlogged plots. Tree height was a much stronger predictor of mortality than stem diameter. In unlogged plots, tree height but not crown exposure was positively associated with drought-induced mortality, whereas in logged plots, neither tree height nor crown exposure was associated with drought-induced mortality. Our results suggest that, at the scale of a site, hydraulic factors related to tree height, not air humidity, are a cause of elevated drought-induced mortality of large trees in unlogged plots.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297479, year = {2018}, author = {Brum, M and Gutiérrez López, J and Asbjornsen, H and Licata, J and Pypker, T and Sanchez, G and Oiveira, RS}, title = {ENSO effects on the transpiration of eastern Amazon trees.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297479}, issn = {1471-2970}, abstract = {Tree transpiration is important in the recycling of precipitation in the Amazon and might be negatively affected by El Niño-Southern Oscillation (ENSO)-induced droughts. To investigate the relative importance of soil moisture deficits versus increasing atmospheric demand (VPD) and determine if these drivers exert different controls over tree transpiration during the wet season versus the dry season (DS), we conducted sap flow measurements in a primary lowland tropical forest in eastern Amazon during the most extreme ENSO-induced drought (2015/2016) recorded in the Amazon. We also assessed whether trees occupying different canopy strata contribute equally to the overall stand transpiration (Tstand). Canopy trees were the primary source of Tstand However, subcanopy trees are still important as they transpired an amount similar to other biomes around the globe. Tree water use was higher during the DS, indicating that during extreme drought trees did not reduce transpiration in response to low soil moisture. Photosynthetically active radiation and VPD exerted an overriding effect on water use patterns relative to soil moisture during extreme drought, indicating that light and atmospheric constraints play a critical role in controlling ecosystem fluxes of water. Our study highlights the importance of canopy and subcanopy trees to the regional water balance and highlights the resilience to droughts that these trees show during an extreme ENSO event.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297478, year = {2018}, author = {van Schaik, E and Killaars, L and Smith, NE and Koren, G and van Beek, LPH and Peters, W and van der Laan-Luijkx, IT}, title = {Changes in surface hydrology, soil moisture and gross primary production in the Amazon during the 2015/2016 El Niño.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297478}, issn = {1471-2970}, abstract = {The 2015/2016 El Niño event caused severe changes in precipitation across the tropics. This impacted surface hydrology, such as river run-off and soil moisture availability, thereby triggering reductions in gross primary production (GPP). Many biosphere models lack the detailed hydrological component required to accurately quantify anomalies in surface hydrology and GPP during droughts in tropical regions. Here, we take the novel approach of coupling the biosphere model SiBCASA with the advanced hydrological model PCR-GLOBWB to attempt such a quantification across the Amazon basin during the drought in 2015/2016. We calculate 30-40% reduced river discharge in the Amazon starting in October 2015, lagging behind the precipitation anomaly by approximately one month and in good agreement with river gauge observations. Soil moisture shows distinctly asymmetrical spatial anomalies with large reductions across the north-eastern part of the basin, which persisted into the following dry season. This added to drought stress in vegetation, already present owing to vapour pressure deficits at the leaf, resulting in a loss of GPP of 0.95 (0.69 to 1.20) PgC between October 2015 and March 2016 compared with the 2007-2014 average. Only 11% (10-12%) of the reduction in GPP was found in the (wetter) north-western part of the basin, whereas the north-eastern and southern regions were affected more strongly, with 56% (54-56%) and 33% (31-33%) of the total, respectively. Uncertainty on this anomaly mostly reflects the unknown rooting depths of vegetation.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297477, year = {2018}, author = {Silva, CVJ and Aragão, LEOC and Barlow, J and Espirito-Santo, F and Young, PJ and Anderson, LO and Berenguer, E and Brasil, I and Foster Brown, I and Castro, B and Farias, R and Ferreira, J and França, F and Graça, PMLA and Kirsten, L and Lopes, AP and Salimon, C and Scaranello, MA and Seixas, M and Souza, FC and Xaud, HAM}, title = {Drought-induced Amazonian wildfires instigate a decadal-scale disruption of forest carbon dynamics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297477}, issn = {1471-2970}, abstract = {Drought-induced wildfires have increased in frequency and extent over the tropics. Yet, the long-term (greater than 10 years) responses of Amazonian lowland forests to fire disturbance are poorly known. To understand post-fire forest biomass dynamics, and to assess the time required for fire-affected forests to recover to pre-disturbance levels, we combined 16 single with 182 multiple forest census into a unique large-scale and long-term dataset across the Brazilian Amazonia. We quantified biomass, mortality and wood productivity of burned plots along a chronosequence of up to 31 years post-fire and compared to surrounding unburned plots measured simultaneously. Stem mortality and growth were assessed among functional groups. At the plot level, we found that fire-affected forests have biomass levels 24.8 ± 6.9% below the biomass value of unburned control plots after 31 years. This lower biomass state results from the elevated levels of biomass loss through mortality, which is not sufficiently compensated for by wood productivity (incremental growth + recruitment). At the stem level, we found major changes in mortality and growth rates up to 11 years post-fire. The post-fire stem mortality rates exceeded unburned control plots by 680% (i.e. greater than 40 cm diameter at breast height (DBH); 5-8 years since last fire) and 315% (i.e. greater than 0.7 g cm-3 wood density; 0.75-4 years since last fire). Our findings indicate that wildfires in humid tropical forests can significantly reduce forest biomass for decades by enhancing mortality rates of all trees, including large and high wood density trees, which store the largest amount of biomass in old-growth forests. This assessment of stem dynamics, therefore, demonstrates that wildfires slow down or stall the post-fire recovery of Amazonian forests.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297476, year = {2018}, author = {Anderson, LO and Ribeiro Neto, G and Cunha, AP and Fonseca, MG and Mendes de Moura, Y and Dalagnol, R and Wagner, FH and de Aragão, LEOEC}, title = {Vulnerability of Amazonian forests to repeated droughts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297476}, issn = {1471-2970}, abstract = {Extreme droughts have been recurrent in the Amazon over the past decades, causing socio-economic and environmental impacts. Here, we investigate the vulnerability of Amazonian forests, both undisturbed and human-modified, to repeated droughts. We defined vulnerability as a measure of (i) exposure, which is the degree to which these ecosystems were exposed to droughts, and (ii) its sensitivity, measured as the degree to which the drought has affected remote sensing-derived forest greenness. The exposure was calculated by assessing the meteorological drought, using the standardized precipitation index (SPI) and the maximum cumulative water deficit (MCWD), which is related to vegetation water stress, from 1981 to 2016. The sensitivity was assessed based on the enhanced vegetation index anomalies (AEVI), derived from the newly available Moderate Resolution Imaging Spectroradiometer (MODIS)/Multi-Angle Implementation of Atmospheric Correction algorithm (MAIAC) product, from 2003 to 2016, which is indicative of forest's photosynthetic capacity. We estimated that 46% of the Brazilian Amazon biome was under severe to extreme drought in 2015/2016 as measured by the SPI, compared with 16% and 8% for the 2009/2010 and 2004/2005 droughts, respectively. The most recent drought (2015/2016) affected the largest area since the drought of 1981. Droughts tend to increase the variance of the photosynthetic capacity of Amazonian forests as based on the minimum and maximum AEVI analysis. However, the area showing a reduction in photosynthetic capacity prevails in the signal, reaching more than 400 000 km2 of forests, four orders of magnitude larger than areas with AEVI enhancement. Moreover, the intensity of the negative AEVI steadily increased from 2005 to 2016. These results indicate that during the analysed period drought impacts were being exacerbated through time. Forests in the twenty-first century are becoming more vulnerable to droughts, with larger areas intensively and negatively responding to water shortage in the region.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297475, year = {2018}, author = {Rifai, SW and Girardin, CAJ and Berenguer, E and Del Aguila-Pasquel, J and Dahlsjö, CAL and Doughty, CE and Jeffery, KJ and Moore, S and Oliveras, I and Riutta, T and Rowland, LM and Murakami, AA and Addo-Danso, SD and Brando, P and Burton, C and Ondo, FE and Duah-Gyamfi, A and Amézquita, FF and Freitag, R and Pacha, FH and Huasco, WH and Ibrahim, F and Mbou, AT and Mihindou, VM and Peixoto, KS and Rocha, W and Rossi, LC and Seixas, M and Silva-Espejo, JE and Abernethy, KA and Adu-Bredu, S and Barlow, J and da Costa, ACL and Marimon, BS and Marimon-Junior, BH and Meir, P and Metcalfe, DB and Phillips, OL and White, LJT and Malhi, Y}, title = {ENSO Drives interannual variation of forest woody growth across the tropics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297475}, issn = {1471-2970}, abstract = {Meteorological extreme events such as El Niño events are expected to affect tropical forest net primary production (NPP) and woody growth, but there has been no large-scale empirical validation of this expectation. We collected a large high-temporal resolution dataset (for 1-13 years depending upon location) of more than 172 000 stem growth measurements using dendrometer bands from across 14 regions spanning Amazonia, Africa and Borneo in order to test how much month-to-month variation in stand-level woody growth of adult tree stems (NPPstem) can be explained by seasonal variation and interannual meteorological anomalies. A key finding is that woody growth responds differently to meteorological variation between tropical forests with a dry season (where monthly rainfall is less than 100 mm), and aseasonal wet forests lacking a consistent dry season. In seasonal tropical forests, a high degree of variation in woody growth can be predicted from seasonal variation in temperature, vapour pressure deficit, in addition to anomalies of soil water deficit and shortwave radiation. The variation of aseasonal wet forest woody growth is best predicted by the anomalies of vapour pressure deficit, water deficit and shortwave radiation. In total, we predict the total live woody production of the global tropical forest biome to be 2.16 Pg C yr-1, with an interannual range 1.96-2.26 Pg C yr-1 between 1996-2016, and with the sharpest declines during the strong El Niño events of 1997/8 and 2015/6. There is high geographical variation in hotspots of El Niño-associated impacts, with weak impacts in Africa, and strongly negative impacts in parts of Southeast Asia and extensive regions across central and eastern Amazonia. Overall, there is high correlation (r = -0.75) between the annual anomaly of tropical forest woody growth and the annual mean of the El Niño 3.4 index, driven mainly by strong correlations with anomalies of soil water deficit, vapour pressure deficit and shortwave radiation.This article is part of the discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297474, year = {2018}, author = {Luo, X and Keenan, TF and Fisher, JB and Jiménez-Muñoz, JC and Chen, JM and Jiang, C and Ju, W and Perakalapudi, NV and Ryu, Y and Tadić, JM}, title = {The impact of the 2015/2016 El Niño on global photosynthesis using satellite remote sensing.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297474}, issn = {1471-2970}, abstract = {The El Niño-Southern Oscillation exerts a large influence on global climate regimes and on the global carbon cycle. Although El Niño is known to be associated with a reduction of the global total land carbon sink, results based on prognostic models or measurements disagree over the relative contribution of photosynthesis to the reduced sink. Here, we provide an independent remote sensing-based analysis on the impact of the 2015-2016 El Niño on global photosynthesis using six global satellite-based photosynthesis products and a global solar-induced fluorescence (SIF) dataset. An ensemble of satellite-based photosynthesis products showed a negative anomaly of -0.7 ± 1.2 PgC in 2015, but a slight positive anomaly of 0.05 ± 0.89 PgC in 2016, which when combined with observations of the growth rate of atmospheric carbon dioxide concentrations suggests that the reduction of the land residual sink was likely dominated by photosynthesis in 2015 but by respiration in 2016. The six satellite-based products unanimously identified a major photosynthesis reduction of -1.1 ± 0.52 PgC from savannahs in 2015 and 2016, followed by a highly uncertain reduction of -0.22 ± 0.98 PgC from rainforests. Vegetation in the Northern Hemisphere enhanced photosynthesis before and after the peak El Niño, especially in grasslands (0.33 ± 0.13 PgC). The patterns of satellite-based photosynthesis ensemble mean were corroborated by SIF, except in rainforests and South America, where the anomalies of satellite-based photosynthesis products also diverged the most. We found the inter-model variation of photosynthesis estimates was strongly related to the discrepancy between moisture forcings for models. These results highlight the importance of considering multiple photosynthesis proxies when assessing responses to climatic anomalies.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297473, year = {2018}, author = {Koren, G and van Schaik, E and Araújo, AC and Boersma, KF and Gärtner, A and Killaars, L and Kooreman, ML and Kruijt, B and van der Laan-Luijkx, IT and von Randow, C and Smith, NE and Peters, W}, title = {Widespread reduction in sun-induced fluorescence from the Amazon during the 2015/2016 El Niño.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297473}, issn = {1471-2970}, abstract = {The tropical carbon balance dominates year-to-year variations in the CO2 exchange with the atmosphere through photosynthesis, respiration and fires. Because of its high correlation with gross primary productivity (GPP), observations of sun-induced fluorescence (SIF) are of great interest. We developed a new remotely sensed SIF product with improved signal-to-noise in the tropics, and use it here to quantify the impact of the 2015/2016 El Niño Amazon drought. We find that SIF was strongly suppressed over areas with anomalously high temperatures and decreased levels of water in the soil. SIF went below its climatological range starting from the end of the 2015 dry season (October) and returned to normal levels by February 2016 when atmospheric conditions returned to normal, but well before the end of anomalously low precipitation that persisted through June 2016. Impacts were not uniform across the Amazon basin, with the eastern part experiencing much larger (10-15%) SIF reductions than the western part of the basin (2-5%). We estimate the integrated loss of GPP relative to eight previous years to be 0.34-0.48 PgC in the three-month period October-November-December 2015.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297472, year = {2018}, author = {Palmer, PI}, title = {The role of satellite observations in understanding the impact of El Niño on the carbon cycle: current capabilities and future opportunities.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297472}, issn = {1471-2970}, abstract = {The 2015/2016 El Niño was the first major climate variation when there were a range of satellite observations that simultaneously observed land, ocean and atmospheric properties associated with the carbon cycle. These data are beginning to provide new insights into the varied responses of land ecosystems to El Niño, but we are far from fully exploiting the information embodied by these data. Here, we briefly review the atmospheric and terrestrial satellite data that are available to study the carbon cycle. We also outline recommendations for future research, particularly the closer integration of satellite data with forest biometric datasets that provide detailed information about carbon dynamics on a range of timescales.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297471, year = {2018}, author = {Burton, C and Rifai, S and Malhi, Y}, title = {Inter-comparison and assessment of gridded climate products over tropical forests during the 2015/2016 El Niño.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297471}, issn = {1471-2970}, abstract = {To understand the impacts of extreme climate events, it is first necessary to understand the spatio-temporal characteristics of the event. Gridded climate products are frequently used to describe climate patterns but have been shown to perform poorly over data-sparse regions such as tropical forests. Often, they are uncritically employed in a wide range of studies linking tropical forest processes to large-scale climate variability. Here, we conduct an inter-comparison and assessment of near-surface air temperature fields supplied by four state-of-the-art reanalysis products, along with precipitation estimates supplied by four merged satellite-gauge rainfall products. Firstly, spatio-temporal patterns of temperature and precipitation anomalies during the 2015-2016 El Niño are shown for each product to characterize the impact of the El Niño on the tropical forest biomes of Equatorial Africa, Southeast Asia and South America. Using meteorological station data, a two-stage assessment is then conducted to determine which products most reliably model tropical climates during the 2015-2016 El Niño, and which perform best over the longer-term satellite observation period (1980-2016). Results suggest that eastern Amazonia, parts of the Congo Basin and mainland Southeast Asia all experienced significant monthly mean temperature anomalies during the El Niño, while northeastern Amazonia, eastern Borneo and southern New Guinea experienced significant precipitation deficits. Our results suggest ERA-Interim and MERRA2 are the most reliable air temperature datasets, while TRMM 3B42 V7 and CHIRPS v2.0 are the best-performing rainfall datasets.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297470, year = {2018}, author = {Eller, CB and Rowland, L and Oliveira, RS and Bittencourt, PRL and Barros, FV and da Costa, ACL and Meir, P and Friend, AD and Mencuccini, M and Sitch, S and Cox, P}, title = {Modelling tropical forest responses to drought and El Niño with a stomatal optimization model based on xylem hydraulics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297470}, issn = {1471-2970}, abstract = {The current generation of dynamic global vegetation models (DGVMs) lacks a mechanistic representation of vegetation responses to soil drought, impairing their ability to accurately predict Earth system responses to future climate scenarios and climatic anomalies, such as El Niño events. We propose a simple numerical approach to model plant responses to drought coupling stomatal optimality theory and plant hydraulics that can be used in dynamic global vegetation models (DGVMs). The model is validated against stand-scale forest transpiration (E) observations from a long-term soil drought experiment and used to predict the response of three Amazonian forest sites to climatic anomalies during the twentieth century. We show that our stomatal optimization model produces realistic stomatal responses to environmental conditions and can accurately simulate how tropical forest E responds to seasonal, and even long-term soil drought. Our model predicts a stronger cumulative effect of climatic anomalies in Amazon forest sites exposed to soil drought during El Niño years than can be captured by alternative empirical drought representation schemes. The contrasting responses between our model and empirical drought factors highlight the utility of hydraulically-based stomatal optimization models to represent vegetation responses to drought and climatic anomalies in DGVMs.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297469, year = {2018}, author = {Withey, K and Berenguer, E and Palmeira, AF and Espírito-Santo, FDB and Lennox, GD and Silva, CVJ and Aragão, LEOC and Ferreira, J and França, F and Malhi, Y and Rossi, LC and Barlow, J}, title = {Quantifying immediate carbon emissions from El Niño-mediated wildfires in humid tropical forests.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297469}, issn = {1471-2970}, abstract = {Wildfires produce substantial CO2 emissions in the humid tropics during El Niño-mediated extreme droughts, and these emissions are expected to increase in coming decades. Immediate carbon emissions from uncontrolled wildfires in human-modified tropical forests can be considerable owing to high necromass fuel loads. Yet, data on necromass combustion during wildfires are severely lacking. Here, we evaluated necromass carbon stocks before and after the 2015-2016 El Niño in Amazonian forests distributed along a gradient of prior human disturbance. We then used Landsat-derived burn scars to extrapolate regional immediate wildfire CO2 emissions during the 2015-2016 El Niño. Before the El Niño, necromass stocks varied significantly with respect to prior disturbance and were largest in undisturbed primary forests (30.2 ± 2.1 Mg ha-1, mean ± s.e.) and smallest in secondary forests (15.6 ± 3.0 Mg ha-1). However, neither prior disturbance nor our proxy of fire intensity (median char height) explained necromass losses due to wildfires. In our 6.5 million hectare (6.5 Mha) study region, almost 1 Mha of primary (disturbed and undisturbed) and 20 000 ha of secondary forest burned during the 2015-2016 El Niño. Covering less than 0.2% of Brazilian Amazonia, these wildfires resulted in expected immediate CO2 emissions of approximately 30 Tg, three to four times greater than comparable estimates from global fire emissions databases. Uncontrolled understorey wildfires in humid tropical forests during extreme droughts are a large and poorly quantified source of CO2 emissions.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297468, year = {2018}, author = {Meir, P and Mencuccini, M and Binks, O and da Costa, AL and Ferreira, L and Rowland, L}, title = {Short-term effects of drought on tropical forest do not fully predict impacts of repeated or long-term drought: gas exchange versus growth.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297468}, issn = {1471-2970}, abstract = {Are short-term responses by tropical rainforest to drought (e.g. during El Niño) sufficient to predict changes over the long-term, or from repeated drought? Using the world's only long-term (16-year) drought experiment in tropical forest we examine predictability from short-term measurements (1-2 years). Transpiration was maximized in droughted forest: it consumed all available throughfall throughout the 16 years of study. Leaf photosynthetic capacity [Formula: see text] was maintained, but only when averaged across tree size groups. Annual transpiration in droughted forest was less than in control, with initial reductions (at high biomass) imposed by foliar stomatal control. Tree mortality increased after year three, leading to an overall biomass loss of 40%; over the long-term, the main constraint on transpiration was thus imposed by the associated reduction in sapwood area. Altered tree mortality risk may prove predictable from soil and plant hydraulics, but additional monitoring is needed to test whether future biomass will stabilize or collapse. Allocation of assimilate differed over time: stem growth and reproductive output declined in the short-term, but following mortality-related changes in resource availability, both showed long-term resilience, with partial or full recovery. Understanding and simulation of these phenomena and related trade-offs in allocation will advance more effectively through greater use of optimization and probabilistic modelling approaches.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297467, year = {2018}, author = {Berenguer, E and Malhi, Y and Brando, P and Cardoso Nunes Cordeiro, A and Ferreira, J and França, F and Chesini Rossi, L and Maria Moraes de Seixas, M and Barlow, J}, title = {Tree growth and stem carbon accumulation in human-modified Amazonian forests following drought and fire.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297467}, issn = {1471-2970}, abstract = {Human-modified forests are an ever-increasing feature across the Amazon Basin, but little is known about how stem growth is influenced by extreme climatic events and the resulting wildfires. Here we assess for the first time the impacts of human-driven disturbance in combination with El Niño-mediated droughts and fires on tree growth and carbon accumulation. We found that after 2.5 years of continuous measurements, there was no difference in stem carbon accumulation between undisturbed and human-modified forests. Furthermore, the extreme drought caused by the El Niño did not affect carbon accumulation rates in surviving trees. In recently burned forests, trees grew significantly more than in unburned ones, regardless of their history of previous human disturbance. Wood density was the only significant factor that helped explain the difference in growth between trees in burned and unburned forests, with low wood-density trees growing significantly more in burned sites. Our results suggest stem carbon accumulation is resistant to human disturbance and one-off extreme drought events, and it is stimulated immediately after wildfires. However, these results should be seen with caution-without accounting for carbon losses, recruitment and longer-term changes in species composition, we cannot fully understand the impacts of drought and fire in the carbon balance of human-modified forests.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Nino on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297466, year = {2018}, author = {Nechita-Banda, N and Krol, M and van der Werf, GR and Kaiser, JW and Pandey, S and Huijnen, V and Clerbaux, C and Coheur, P and Deeter, MN and Röckmann, T}, title = {Monitoring emissions from the 2015 Indonesian fires using CO satellite data.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297466}, issn = {1471-2970}, abstract = {Southeast Asia, in particular Indonesia, has periodically struggled with intense fire events. These events convert substantial amounts of carbon stored as peat to atmospheric carbon dioxide (CO2) and significantly affect atmospheric composition on a regional to global scale. During the recent 2015 El Niño event, peat fires led to strong enhancements of carbon monoxide (CO), an air pollutant and well-known tracer for biomass burning. These enhancements were clearly observed from space by the Infrared Atmospheric Sounding Interferometer (IASI) and the Measurements of Pollution in the Troposphere (MOPITT) instruments. We use these satellite observations to estimate CO fire emissions within an inverse modelling framework. We find that the derived CO emissions for each sub-region of Indonesia and Papua are substantially different from emission inventories, highlighting uncertainties in bottom-up estimates. CO fire emissions based on either MOPITT or IASI have a similar spatial pattern and evolution in time, and a 10% uncertainty based on a set of sensitivity tests we performed. Thus, CO satellite data have a high potential to complement existing operational fire emission estimates based on satellite observations of fire counts, fire radiative power and burned area, in better constraining fire occurrence and the associated conversion of peat carbon to atmospheric CO2 A total carbon release to the atmosphere of 0.35-0.60 Pg C can be estimated based on our results.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297465, year = {2018}, author = {Bastos, A and Friedlingstein, P and Sitch, S and Chen, C and Mialon, A and Wigneron, JP and Arora, VK and Briggs, PR and Canadell, JG and Ciais, P and Chevallier, F and Cheng, L and Delire, C and Haverd, V and Jain, AK and Joos, F and Kato, E and Lienert, S and Lombardozzi, D and Melton, JR and Myneni, R and Nabel, JEMS and Pongratz, J and Poulter, B and Rödenbeck, C and Séférian, R and Tian, H and van Eck, C and Viovy, N and Vuichard, N and Walker, AP and Wiltshire, A and Yang, J and Zaehle, S and Zeng, N and Zhu, D}, title = {Impact of the 2015/2016 El Niño on the terrestrial carbon cycle constrained by bottom-up and top-down approaches.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297465}, issn = {1471-2970}, support = {610028//European Research Council/International ; }, abstract = {Evaluating the response of the land carbon sink to the anomalies in temperature and drought imposed by El Niño events provides insights into the present-day carbon cycle and its climate-driven variability. It is also a necessary step to build confidence in terrestrial ecosystems models' response to the warming and drying stresses expected in the future over many continents, and particularly in the tropics. Here we present an in-depth analysis of the response of the terrestrial carbon cycle to the 2015/2016 El Niño that imposed extreme warming and dry conditions in the tropics and other sensitive regions. First, we provide a synthesis of the spatio-temporal evolution of anomalies in net land-atmosphere CO2 fluxes estimated by two in situ measurements based on atmospheric inversions and 16 land-surface models (LSMs) from TRENDYv6. Simulated changes in ecosystem productivity, decomposition rates and fire emissions are also investigated. Inversions and LSMs generally agree on the decrease and subsequent recovery of the land sink in response to the onset, peak and demise of El Niño conditions and point to the decreased strength of the land carbon sink: by 0.4-0.7 PgC yr-1 (inversions) and by 1.0 PgC yr-1 (LSMs) during 2015/2016. LSM simulations indicate that a decrease in productivity, rather than increase in respiration, dominated the net biome productivity anomalies in response to ENSO throughout the tropics, mainly associated with prolonged drought conditions.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297464, year = {2018}, author = {Rödenbeck, C and Zaehle, S and Keeling, R and Heimann, M}, title = {History of El Niño impacts on the global carbon cycle 1957-2017: a quantification from atmospheric CO2 data.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297464}, issn = {1471-2970}, abstract = {Interannual variations in the large-scale net ecosystem exchange (NEE) of CO2 between the terrestrial biosphere and the atmosphere were estimated for 1957-2017 from sustained measurements of atmospheric CO2 mixing ratios. As the observations are sparse in the early decades, available records were combined into a 'quasi-homogeneous' dataset based on similarity in their signals, to minimize spurious variations from beginning or ending data records. During El Niño events, CO2 is anomalously released from the tropical band, and a few months later also in the northern extratropical band. This behaviour can approximately be represented by a linear relationship of the NEE anomalies and local air temperature anomalies, with sensitivity coefficients depending on geographical location and season. The apparent climate sensitivity of global total NEE against variations in pan-tropically averaged annual air temperature slowly changed over time during the 1957-2017 period, first increasing (though less strongly than in previous studies) but then decreasing again. However, only part of this change can be attributed to actual changes in local physiological or ecosystem processes, the rest probably arising from shifts in the geographical area of dominating temperature variations.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297463, year = {2018}, author = {Gloor, E and Wilson, C and Chipperfield, MP and Chevallier, F and Buermann, W and Boesch, H and Parker, R and Somkuti, P and Gatti, LV and Correia, C and Domingues, LG and Peters, W and Miller, J and Deeter, MN and Sullivan, MJP}, title = {Tropical land carbon cycle responses to 2015/16 El Niño as recorded by atmospheric greenhouse gas and remote sensing data.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297463}, issn = {1471-2970}, abstract = {The outstanding tropical land climate characteristic over the past decades is rapid warming, with no significant large-scale precipitation trends. This warming is expected to continue but the effects on tropical vegetation are unknown. El Niño-related heat peaks may provide a test bed for a future hotter world. Here we analyse tropical land carbon cycle responses to the 2015/16 El Niño heat and drought anomalies using an atmospheric transport inversion. Based on the global atmospheric CO2 and fossil fuel emission records, we find no obvious signs of anomalously large carbon release compared with earlier El Niño events, suggesting resilience of tropical vegetation. We find roughly equal net carbon release anomalies from Amazonia and tropical Africa, approximately 0.5 PgC each, and smaller carbon release anomalies from tropical East Asia and southern Africa. Atmospheric CO anomalies reveal substantial fire carbon release from tropical East Asia peaking in October 2015 while fires contribute only a minor amount to the Amazonian carbon flux anomaly. Anomalously large Amazonian carbon flux release is consistent with downregulation of primary productivity during peak negative near-surface water anomaly (October 2015 to March 2016) as diagnosed by solar-induced fluorescence. Finally, we find an unexpected anomalous positive flux to the atmosphere from tropical Africa early in 2016, coincident with substantial CO release.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297462, year = {2018}, author = {Betts, RA and Jones, CD and Knight, JR and Keeling, RF and Kennedy, JJ and Wiltshire, AJ and Andrew, RM and Aragão, LEOC}, title = {A successful prediction of the record CO2 rise associated with the 2015/2016 El Niño.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297462}, issn = {1471-2970}, abstract = {In early 2016, we predicted that the annual rise in carbon dioxide concentration at Mauna Loa would be the largest on record. Our forecast used a statistical relationship between observed and forecast sea surface temperatures in the Niño 3.4 region and the annual CO2 rise. Here, we provide a formal verification of that forecast. The observed rise of 3.4 ppm relative to 2015 was within the forecast range of 3.15 ± 0.53 ppm, so the prediction was successful. A global terrestrial biosphere model supports the expectation that the El Niño weakened the tropical land carbon sink. We estimate that the El Niño contributed approximately 25% to the record rise in CO2, with 75% due to anthropogenic emissions. The 2015/2016 CO2 rise was greater than that following the previous large El Niño in 1997/1998, because anthropogenic emissions had increased. We had also correctly predicted that 2016 would be the first year with monthly mean CO2 above 400 ppm all year round. We now estimate that atmospheric CO2 at Mauna Loa would have remained above 400 ppm all year round in 2016 even if the El Niño had not occurred, contrary to our previous expectations based on a simple extrapolation of previous trends.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297461, year = {2018}, author = {Jimenez, JC and Barichivich, J and Mattar, C and Takahashi, K and Santamaría-Artigas, A and Sobrino, JA and Malhi, Y}, title = {Spatio-temporal patterns of thermal anomalies and drought over tropical forests driven by recent extreme climatic anomalies.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297461}, issn = {1471-2970}, abstract = {The recent 2015-2016 El Niño (EN) event was considered as strong as the EN in 1997-1998. Given such magnitude, it was expected to result in extreme warming and moisture anomalies in tropical areas. Here we characterize the spatial patterns of temperature anomalies and drought over tropical forests, including tropical South America (Amazonia), Africa and Asia/Indonesia during the 2015-2016 EN event. These spatial patterns of warming and drought are compared with those observed in previous strong EN events (1982-1983 and 1997-1998) and other moderate to strong EN events (e.g. 2004-2005 and 2009-2010). The link between the spatial patterns of drought and sea surface temperature anomalies in the central and eastern Pacific is also explored. We show that indeed the EN2015-2016 led to unprecedented warming compared to the other EN events over Amazonia, Africa and Indonesia, as a consequence of the background global warming trend. Anomalous accumulated extreme drought area over Amazonia was found during EN2015-2016, but this value may be closer to extreme drought area extents in the other two EN events in 1982-1983 and 1997-1998. Over Africa, datasets disagree, and it is difficult to conclude which EN event led to the highest accumulated extreme drought area. Our results show that the highest values of accumulated drought area over Africa were obtained in 2015-2016 and 1997-1998, with a long-term drying trend not observed over the other tropical regions. Over Indonesia, all datasets suggest that EN 1982-1983 and EN 1997-1998 (or even the drought of 2005) led to a higher extreme drought area than EN2015-2016. Uncertainties in precipitation datasets hinder consistent estimates of drought severity over tropical regions, and improved reanalysis products and station records are required.This article is part of a discussion meeting issue 'The impact of the 2015/2016 El Niño on the terrestrial tropical carbon cycle: patterns, mechanisms and implications'.}, } @article {pmid30297460, year = {2018}, author = {Malhi, Y and Rowland, L and Aragão, LEOC and Fisher, RA}, title = {New insights into the variability of the tropical land carbon cycle from the El Niño of 2015/2016.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1760}, pages = {}, pmid = {30297460}, issn = {1471-2970}, } @article {pmid30297433, year = {2018}, author = {Nagahama, Y and Shimoda, M and Mao, G and Singh, SK and Kozakai, Y and Sun, X and Motooka, D and Nakamura, S and Tanaka, H and Satoh, T and Maeda, K and Akira, S}, title = {Regnase-1 controls colon epithelial regeneration via regulation of mTOR and purine metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11036-11041}, pmid = {30297433}, issn = {1091-6490}, mesh = {Animals ; Apoptosis/physiology ; Cell Proliferation/physiology ; Colitis/metabolism ; Colon/*metabolism ; Disease Models, Animal ; Epithelial Cells/*metabolism ; Inflammation/metabolism ; Inflammatory Bowel Diseases/metabolism ; Intestinal Mucosa/*metabolism ; Mice ; Purines/*metabolism ; Regeneration/*physiology ; Ribonucleases/*metabolism ; Signal Transduction/physiology ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {Damage to intestinal epithelial cell (IEC) layers during intestinal inflammation is associated with inflammatory bowel disease. Here we show that the endoribonuclease Regnase-1 controls colon epithelial regeneration by regulating protein kinase mTOR (the mechanistic target of rapamycin kinase) and purine metabolism. During dextran sulfate sodium-induced intestinal epithelial injury and acute colitis, Regnase-1∆IEC mice, which lack Regnase-1 specifically in the intestinal epithelium, were resistant to body weight loss, maintained an intact intestinal barrier, and showed increased cell proliferation and decreased epithelial apoptosis. Chronic colitis and tumor progression were also attenuated in Regnase-1∆IEC mice. Regnase-1 predominantly regulates mTORC1 signaling. Metabolic analysis revealed that Regnase-1 participates in purine metabolism and energy metabolism during inflammation. Furthermore, increased expression of ectonucleotidases contributed to the resolution of acute inflammation in Regnase-1∆IEC mice. These findings provide evidence that Regnase-1 deficiency has beneficial effects on the prevention and/or blocking of intestinal inflammatory disorders.}, } @article {pmid30297432, year = {2018}, author = {Knorr, DA and Dahan, R and Ravetch, JV}, title = {Toxicity of an Fc-engineered anti-CD40 antibody is abrogated by intratumoral injection and results in durable antitumor immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11048-11053}, pmid = {30297432}, issn = {1091-6490}, support = {P01 CA190174/CA/NCI NIH HHS/United States ; R35 CA196620/CA/NCI NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*immunology ; CD40 Antigens/*immunology ; CTLA-4 Antigen/immunology ; Cell Line, Tumor ; Humans ; Immunoglobulin Fc Fragments/*immunology ; Immunotherapy/methods ; Injections, Intralesional/methods ; Mice ; }, abstract = {Immune stimulation has emerged as a promising approach to the treatment of neoplastic diseases. Currently approved therapeutics, such as anti-CTLA4 and anti-PD1, are primarily aimed at blocking inhibitory signaling by immune cells. An alternative and potentially synergistic approach would involve activation of immune pathways by agonism of stimulatory receptors, such as CD40. Agonistic antibodies, while promising in principle, have encountered significant barriers in clinical trials limited by the systemic toxicity of such approaches. Using a mouse model humanized for both Fc receptors and CD40, we previously demonstrated enhanced antitumor activity with an Fc-modified antibody. We now demonstrate that this model recapitulates the platelet and hepatic toxicities seen with anti-CD40 antibodies in patients, providing a predictive measure of the dose-limiting activity of this approach. We further show that such toxicity can be circumvented and durable systemic antitumor immunity achieved by intratumoral delivery of an Fc-engineered anti-CD40 agonistic antibody.}, } @article {pmid30297431, year = {2018}, author = {Lian, B and Sun, XQ and Vaezi, A and Qi, XL and Zhang, SC}, title = {Topological quantum computation based on chiral Majorana fermions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10938-10942}, pmid = {30297431}, issn = {1091-6490}, abstract = {The chiral Majorana fermion is a massless self-conjugate fermion which can arise as the edge state of certain 2D topological matters. It has been theoretically predicted and experimentally observed in a hybrid device of a quantum anomalous Hall insulator and a conventional superconductor. Its closely related cousin, the Majorana zero mode in the bulk of the corresponding topological matter, is known to be applicable in topological quantum computations. Here we show that the propagation of chiral Majorana fermions leads to the same unitary transformation as that in the braiding of Majorana zero modes and propose a platform to perform quantum computation with chiral Majorana fermions. A Corbino ring junction of the hybrid device can use quantum coherent chiral Majorana fermions to implement the Hadamard gate and the phase gate, and the junction conductance yields a natural readout for the qubit state.}, } @article {pmid30297430, year = {2018}, author = {Denison, RN and Adler, WT and Carrasco, M and Ma, WJ}, title = {Humans incorporate attention-dependent uncertainty into perceptual decisions and confidence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11090-11095}, pmid = {30297430}, issn = {1091-6490}, support = {F32 EY025533/EY/NEI NIH HHS/United States ; T32 EY007136/EY/NEI NIH HHS/United States ; }, mesh = {Attention/*physiology ; Bayes Theorem ; Cognition/physiology ; Decision Making/*physiology ; Female ; Humans ; Male ; Orientation/physiology ; Task Performance and Analysis ; Uncertainty ; Visual Perception/physiology ; }, abstract = {Perceptual decisions are better when they take uncertainty into account. Uncertainty arises not only from the properties of sensory input but also from cognitive sources, such as different levels of attention. However, it is unknown whether humans appropriately adjust for such cognitive sources of uncertainty during perceptual decision-making. Here we show that, in a task in which uncertainty is relevant for performance, human categorization and confidence decisions take into account uncertainty related to attention. We manipulated uncertainty in an orientation categorization task from trial to trial using only an attentional cue. The categorization task was designed to disambiguate decision rules that did or did not depend on attention. Using formal model comparison to evaluate decision behavior, we found that category and confidence decision boundaries shifted as a function of attention in an approximately Bayesian fashion. This means that the observer's attentional state on each trial contributed probabilistically to the decision computation. This responsiveness of an observer's decisions to attention-dependent uncertainty should improve perceptual decisions in natural vision, in which attention is unevenly distributed across a scene.}, } @article {pmid30297429, year = {2018}, author = {Cai, S and Chen, C and Tan, ZY and Huang, Y and Shi, J and Gan, L}, title = {Cryo-ET reveals the macromolecular reorganization of S. pombe mitotic chromosomes in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10977-10982}, pmid = {30297429}, issn = {1091-6490}, mesh = {Chromatin/genetics ; Chromosomes/*genetics ; Cryoelectron Microscopy/methods ; Electron Microscope Tomography/methods ; Interphase/genetics ; Macromolecular Substances/*metabolism ; Mitosis/*genetics ; Nucleosomes/genetics ; Schizosaccharomyces/*genetics ; Transcription, Genetic/genetics ; Up-Regulation/genetics ; }, abstract = {Chromosomes condense during mitosis in most eukaryotes. This transformation involves rearrangements at the nucleosome level and has consequences for transcription. Here, we use cryo-electron tomography (cryo-ET) to determine the 3D arrangement of nuclear macromolecular complexes, including nucleosomes, in frozen-hydrated Schizosaccharomyces pombe cells. Using 3D classification analysis, we did not find evidence that nucleosomes resembling the crystal structure are abundant. This observation and those from other groups support the notion that a subset of fission yeast nucleosomes may be partially unwrapped in vivo. In both interphase and mitotic cells, there is also no evidence of monolithic structures the size of Hi-C domains. The chromatin is mingled with two features: pockets, which are positions free of macromolecular complexes; and "megacomplexes," which are multimegadalton globular complexes like preribosomes. Mitotic chromatin is more crowded than interphase chromatin in subtle ways. Nearest-neighbor distance analyses show that mitotic chromatin is more compacted at the oligonucleosome than the dinucleosome level. Like interphase, mitotic chromosomes contain megacomplexes and pockets. This uneven chromosome condensation helps explain a longstanding enigma of mitosis: a subset of genes is up-regulated.}, } @article {pmid30297428, year = {2018}, author = {Jorgenson, E and Matharu, N and Palmer, MR and Yin, J and Shan, J and Hoffmann, TJ and Thai, KK and Zhou, X and Hotaling, JM and Jarvik, GP and Ahituv, N and Wessells, H and Van Den Eeden, SK}, title = {Genetic variation in the SIM1 locus is associated with erectile dysfunction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11018-11023}, pmid = {30297428}, issn = {1091-6490}, support = {RC2 AG036607/AG/NIA NIH HHS/United States ; UM1 HG009408/HG/NHGRI NIH HHS/United States ; P01 HD084387/HD/NICHD NIH HHS/United States ; R01 MH109907/MH/NIMH NIH HHS/United States ; R01 DK104764/DK/NIDDK NIH HHS/United States ; R01 EY027004/EY/NEI NIH HHS/United States ; R01 DK090382/DK/NIDDK NIH HHS/United States ; R01 HL138424/HL/NHLBI NIH HHS/United States ; }, mesh = {Aged ; Alleles ; Body Mass Index ; Case-Control Studies ; Chromosomes, Human, Pair 6/genetics ; Cohort Studies ; Erectile Dysfunction/*genetics ; Genetic Predisposition to Disease/*genetics ; Genetic Variation/*genetics ; Humans ; Leptin/genetics ; Male ; Melanocortins/genetics ; Middle Aged ; Promoter Regions, Genetic/genetics ; }, abstract = {Erectile dysfunction affects millions of men worldwide. Twin studies support the role of genetic risk factors underlying erectile dysfunction, but no specific genetic variants have been identified. We conducted a large-scale genome-wide association study of erectile dysfunction in 36,649 men in the multiethnic Kaiser Permanente Northern California Genetic Epidemiology Research in Adult Health and Aging cohort. We also undertook replication analyses in 222,358 men from the UK Biobank. In the discovery cohort, we identified a single locus (rs17185536-T) on chromosome 6 near the single-minded family basic helix-loop-helix transcription factor 1 (SIM1) gene that was significantly associated with the risk of erectile dysfunction (odds ratio = 1.26, P = 3.4 × 10-25). The association replicated in the UK Biobank sample (odds ratio = 1.25, P = 6.8 × 10-14), and the effect is independent of known erectile dysfunction risk factors, including body mass index (BMI). The risk locus resides on the same topologically associating domain as SIM1 and interacts with the SIM1 promoter, and the rs17185536-T risk allele showed differential enhancer activity. SIM1 is part of the leptin-melanocortin system, which has an established role in body weight homeostasis and sexual function. Because the variants associated with erectile dysfunction are not associated with differences in BMI, our findings suggest a mechanism that is specific to sexual function.}, } @article {pmid30297427, year = {2018}, author = {Azar, B}, title = {Profile of Mary E. Hatten.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10537-10539}, pmid = {30297427}, issn = {1091-6490}, mesh = {Developmental Disabilities/*history ; History, 20th Century ; History, 21st Century ; Humans ; *Neurodevelopmental Disorders ; Neurosciences/*history ; }, } @article {pmid30297426, year = {2018}, author = {Zeng, H and Lu, B and Zamponi, R and Yang, Z and Wetzel, K and Loureiro, J and Mohammadi, S and Beibel, M and Bergling, S and Reece-Hoyes, J and Russ, C and Roma, G and Tchorz, JS and Capodieci, P and Cong, F}, title = {mTORC1 signaling suppresses Wnt/β-catenin signaling through DVL-dependent regulation of Wnt receptor FZD level.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10362-E10369}, pmid = {30297426}, issn = {1091-6490}, mesh = {Adaptor Protein Complex 2/metabolism ; Animals ; Cell Line ; Dishevelled Proteins/metabolism ; Down-Regulation/physiology ; Frizzled Receptors/*metabolism ; Gene Expression/physiology ; HEK293 Cells ; Humans ; Mice ; Receptors, Wnt/*metabolism ; TOR Serine-Threonine Kinases/*metabolism ; Wnt Proteins/*metabolism ; Wnt Signaling Pathway/*physiology ; beta Catenin/*metabolism ; }, abstract = {Wnt/β-catenin signaling plays pivotal roles in cell proliferation and tissue homeostasis by maintaining somatic stem cell functions. The mammalian target of rapamycin (mTOR) signaling functions as an integrative rheostat that orchestrates various cellular and metabolic activities that shape tissue homeostasis. Whether these two fundamental signaling pathways couple to exert physiological functions still remains mysterious. Using a genome-wide CRISPR-Cas9 screening, we discover that mTOR complex 1 (mTORC1) signaling suppresses canonical Wnt/β-catenin signaling. Deficiency in tuberous sclerosis complex 1/2 (TSC1/2), core negative regulators of mTORC1 activity, represses Wnt/β-catenin target gene expression, which can be rescued by RAD001. Mechanistically, mTORC1 signaling regulates the cell surface level of Wnt receptor Frizzled (FZD) in a Dishevelled (DVL)-dependent manner by influencing the association of DVL and clathrin AP-2 adaptor. Sustained mTORC1 activation impairs Wnt/β-catenin signaling and causes loss of stemness in intestinal organoids ex vivo and primitive intestinal progenitors in vivo. Wnt/β-catenin-dependent liver metabolic zonation gene expression program is also down-regulated by mTORC1 activation. Our study provides a paradigm that mTORC1 signaling cell autonomously regulates Wnt/β-catenin pathway to influence stem cell maintenance.}, } @article {pmid30297425, year = {2018}, author = {Rivas-Carrillo, SD and Pettersson, ME and Rubin, CJ and Jern, P}, title = {Whole-genome comparison of endogenous retrovirus segregation across wild and domestic host species populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11012-11017}, pmid = {30297425}, issn = {1091-6490}, mesh = {Animals ; Animals, Domestic/*virology ; Comparative Genomic Hybridization/methods ; DNA/genetics ; Endogenous Retroviruses/*genetics ; Genome, Viral/*genetics ; Genome-Wide Association Study/methods ; Genomics/methods ; Host Specificity/*genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Rabbits ; }, abstract = {Although recent advances in sequencing and computational analyses have facilitated use of endogenous retroviruses (ERVs) for deciphering coevolution among retroviruses and their hosts, sampling effects from different host populations present major challenges. Here we utilize available whole-genome data from wild and domesticated European rabbit (Oryctolagus cuniculus sp.) populations, sequenced as DNA pools by paired-end Illumina technology, for identifying segregating reference as well as nonreference ERV loci, to reveal their variation along the host phylogeny and domestication history. To produce new viruses, retroviruses must insert a proviral DNA copy into the host nuclear DNA. Occasional proviral insertions into the host germline have been passed down through generations as inherited ERVs during millions of years. These ERVs represent retroviruses that were active at the time of infection and thus present a remarkable record of historical virus-host associations. To examine segregating ERVs in host populations, we apply a reference library search strategy for anchoring ERV-associated short-sequence read pairs from pooled whole-genome sequences to reference genome assembly positions. We show that most ERVs segregate along host phylogeny but also uncover radiation of some ERVs, identified as segregating loci among wild and domestic rabbits. The study targets pertinent issues regarding genome sampling when examining virus-host evolution from the genomic ERV record and offers improved scope regarding common strategies for single-nucleotide variant analyses in host population comparative genomics.}, } @article {pmid30297424, year = {2018}, author = {Obradovich, N and Migliorini, R and Paulus, MP and Rahwan, I}, title = {Empirical evidence of mental health risks posed by climate change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10953-10958}, pmid = {30297424}, issn = {1091-6490}, mesh = {Climate Change ; Cross-Sectional Studies ; Cyclonic Storms ; Disasters ; Humans ; Mental Disorders/*etiology/*psychology ; Mental Health ; Prevalence ; Risk ; Weather ; }, abstract = {Sound mental health-a critical facet of human wellbeing-has the potential to be undermined by climate change. Few large-scale studies have empirically examined this hypothesis. Here, we show that short-term exposure to more extreme weather, multiyear warming, and tropical cyclone exposure each associate with worsened mental health. To do so, we couple meteorological and climatic data with reported mental health difficulties drawn from nearly 2 million randomly sampled US residents between 2002 and 2012. We find that shifting from monthly temperatures between 25 °C and 30 °C to >30 °C increases the probability of mental health difficulties by 0.5% points, that 1°C of 5-year warming associates with a 2% point increase in the prevalence of mental health issues, and that exposure to Hurricane Katrina associates with a 4% point increase in this metric. Our analyses provide added quantitative support for the conclusion that environmental stressors produced by climate change pose threats to human mental health.}, } @article {pmid30297423, year = {2018}, author = {Huning, LS and AghaKouchak, A}, title = {Mountain snowpack response to different levels of warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10932-10937}, pmid = {30297423}, issn = {1091-6490}, abstract = {Temperature variability impacts the distribution and persistence of the mountain snowpack, which critically provides snowmelt-derived water resources to large populations worldwide. Warmer temperatures decrease the amount of montane snow water equivalent (SWE), forcing its center of mass to higher elevations. We use a unique multivariate probabilistic framework to quantify the response of the 1 April SWE volume and its centroid to a 1.0 to 2.0 °C increase in winter air temperature across the Sierra Nevada (United States). A 1.0 °C increase reduces the probability of exceeding the long-term (1985-2016) average rangewide SWE volume (15.7 km3) by 20.7%. It correspondingly is 60.6% more likely for the centroid to be higher than its long-term average (2,540 m). We further show that a 1.5 and 2.0 °C increase in the winter temperature reduces the probability of exceeding the long-term average SWE volume by 31.0% and 41.1%, respectively, whereas it becomes 79.3% and 89.8% more likely that the centroid will be higher than 2,540 m for those respective temperature changes. We also characterize regional variability across the Sierra Nevada and show that the northwestern and southeastern regions of the mountain range are 30.3% and 14.0% less likely to have 1 April SWE volumes exceed their long-term average for a 1.0 °C increase about their respective average winter temperatures. Overall, the SWE in the northern Sierra Nevada exhibits higher hydrologic vulnerability to warming than in the southern region. Given the expected increases in mountain temperatures, the observed rates of change in SWE are expected to intensify in the future.}, } @article {pmid30297422, year = {2018}, author = {Ma, H and Leng, S and Aihara, K and Lin, W and Chen, L}, title = {Randomly distributed embedding making short-term high-dimensional data predictable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E9994-E10002}, pmid = {30297422}, issn = {1091-6490}, abstract = {Future state prediction for nonlinear dynamical systems is a challenging task, particularly when only a few time series samples for high-dimensional variables are available from real-world systems. In this work, we propose a model-free framework, named randomly distributed embedding (RDE), to achieve accurate future state prediction based on short-term high-dimensional data. Specifically, from the observed data of high-dimensional variables, the RDE framework randomly generates a sufficient number of low-dimensional "nondelay embeddings" and maps each of them to a "delay embedding," which is constructed from the data of a to be predicted target variable. Any of these mappings can perform as a low-dimensional weak predictor for future state prediction, and all of such mappings generate a distribution of predicted future states. This distribution actually patches all pieces of association information from various embeddings unbiasedly or biasedly into the whole dynamics of the target variable, which after operated by appropriate estimation strategies, creates a stronger predictor for achieving prediction in a more reliable and robust form. Through applying the RDE framework to data from both representative models and real-world systems, we reveal that a high-dimension feature is no longer an obstacle but a source of information crucial to accurate prediction for short-term data, even under noise deterioration.}, } @article {pmid30297421, year = {2018}, author = {Galloway, E and Hauck, T and Corlett, H and Pană, D and Schultz, R}, title = {Faults and associated karst collapse suggest conduits for fluid flow that influence hydraulic fracturing-induced seismicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10003-E10012}, pmid = {30297421}, issn = {1091-6490}, abstract = {During December 2011, a swarm of moderate-magnitude earthquakes was induced by hydraulic fracturing (HF) near Cardston, Alberta. Despite seismological associations linking these two processes, the hydrological and tectonic mechanisms involved remain unclear. In this study, we interpret a 3D reflection-seismic survey to delve into the geological factors related to these earthquakes. First, we document a basement-rooted fault on which the earthquake rupture occurred that extends above the targeted reservoir. Second, at the reservoir's stratigraphic level, anomalous subcircular features are recognized along the fault and are interpreted as resulting from fault-associated karst processes. These observations have implications for HF-induced seismicity, as they suggest hydraulic communication over a large (vertical) distance, reconciling the discrepancy between the culprit well trajectory and earthquake hypocenters. We speculate on how these newly identified geological factors could drive the sporadic appearance of induced seismicity and thus be utilized to avoid earthquake hazards.}, } @article {pmid30297420, year = {2018}, author = {Chen, C and Crivelli, C and Garrod, OGB and Schyns, PG and Fernández-Dols, JM and Jack, RE}, title = {Distinct facial expressions represent pain and pleasure across cultures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10013-E10021}, pmid = {30297420}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 107802/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Cross-Cultural Comparison ; Culture ; Emotions/*physiology ; Face/*physiology ; Facial Expression ; Female ; Humans ; Interpersonal Relations ; Male ; Pain/*physiopathology/*psychology ; Pleasure/*physiology ; Recognition (Psychology)/physiology ; Young Adult ; }, abstract = {Real-world studies show that the facial expressions produced during pain and orgasm-two different and intense affective experiences-are virtually indistinguishable. However, this finding is counterintuitive, because facial expressions are widely considered to be a powerful tool for social interaction. Consequently, debate continues as to whether the facial expressions of these extreme positive and negative affective states serve a communicative function. Here, we address this debate from a novel angle by modeling the mental representations of dynamic facial expressions of pain and orgasm in 40 observers in each of two cultures (Western, East Asian) using a data-driven method. Using a complementary approach of machine learning, an information-theoretic analysis, and a human perceptual discrimination task, we show that mental representations of pain and orgasm are physically and perceptually distinct in each culture. Cross-cultural comparisons also revealed that pain is represented by similar face movements across cultures, whereas orgasm showed distinct cultural accents. Together, our data show that mental representations of the facial expressions of pain and orgasm are distinct, which questions their nondiagnosticity and instead suggests they could be used for communicative purposes. Our results also highlight the potential role of cultural and perceptual factors in shaping the mental representation of these facial expressions. We discuss new research directions to further explore their relationship to the production of facial expressions.}, } @article {pmid30297419, year = {2018}, author = {Lu, CH and Yeh, HY and Su, GC and Ito, K and Kurokawa, Y and Iwasaki, H and Chi, P and Li, HW}, title = {Swi5-Sfr1 stimulates Rad51 recombinase filament assembly by modulating Rad51 dissociation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10059-E10068}, pmid = {30297419}, issn = {1091-6490}, mesh = {Animals ; DNA ; Homologous Recombination/physiology ; Mice ; Nuclear Proteins/*metabolism ; Nucleoproteins/metabolism ; Rad51 Recombinase/*metabolism ; Schizosaccharomyces/metabolism ; }, abstract = {Eukaryotic Rad51 protein is essential for homologous-recombination repair of DNA double-strand breaks. Rad51 recombinases first assemble onto single-stranded DNA to form a nucleoprotein filament, required for function in homology pairing and strand exchange. This filament assembly is the first regulation step in homologous recombination. Rad51 nucleation is kinetically slow, and several accessory factors have been identified to regulate this step. Swi5-Sfr1 (S5S1) stimulates Rad51-mediated homologous recombination by stabilizing Rad51 nucleoprotein filaments, but the mechanism of stabilization is unclear. We used single-molecule tethered particle motion experiments to show that mouse S5S1 (mS5S1) efficiently stimulates mouse RAD51 (mRAD51) nucleus formation and inhibits mRAD51 dissociation from filaments. We also used single-molecule fluorescence resonance energy transfer experiments to show that mS5S1 promotes stable nucleus formation by specifically preventing mRAD51 dissociation. This leads to a reduction of nucleation size from three mRAD51 to two mRAD51 molecules in the presence of mS5S1. Compared with mRAD51, fission yeast Rad51 (SpRad51) exhibits fast nucleation but quickly dissociates from the filament. SpS5S1 specifically reduces SpRad51 disassembly to maintain a stable filament. These results clearly demonstrate the conserved function of S5S1 by primarily stabilizing Rad51 on DNA, allowing both the formation of the stable nucleus and the maintenance of filament length.}, } @article {pmid30297418, year = {2018}, author = {Garrett, AM and Khalil, A and Walton, DO and Burgess, RW}, title = {DSCAM promotes self-avoidance in the developing mouse retina by masking the functions of cadherin superfamily members.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10216-E10224}, pmid = {30297418}, issn = {1091-6490}, support = {F32 EY021942/EY/NEI NIH HHS/United States ; P30 CA034196/CA/NCI NIH HHS/United States ; R01 NS054154/NS/NINDS NIH HHS/United States ; T32 HD007065/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cadherins/*metabolism ; Cell Adhesion/physiology ; Cell Adhesion Molecules/*metabolism ; Cell Line ; Cell Membrane/metabolism ; Choice Behavior/physiology ; Drosophila/metabolism ; Drosophila Proteins/metabolism ; HEK293 Cells ; Humans ; Mice ; Neural Cell Adhesion Molecules/metabolism ; Neurites/metabolism ; Neurogenesis/physiology ; Neurons/metabolism ; Retina/*metabolism ; }, abstract = {During neural development, self-avoidance ensures that a neuron's processes arborize to evenly fill a particular spatial domain. At the individual cell level, self-avoidance is promoted by genes encoding cell-surface molecules capable of generating thousands of diverse isoforms, such as Dscam1 (Down syndrome cell adhesion molecule 1) in Drosophila Isoform choice differs between neighboring cells, allowing neurons to distinguish "self" from "nonself". In the mouse retina, Dscam promotes self-avoidance at the level of cell types, but without extreme isoform diversity. Therefore, we hypothesize that DSCAM is a general self-avoidance cue that "masks" other cell type-specific adhesion systems to prevent overly exuberant adhesion. Here, we provide in vivo and in vitro evidence that DSCAM masks the functions of members of the cadherin superfamily, supporting this hypothesis. Thus, unlike the isoform-rich molecules tasked with self-avoidance at the individual cell level, here the diversity resides on the adhesive side, positioning DSCAM as a generalized modulator of cell adhesion during neural development.}, } @article {pmid30297417, year = {2018}, author = {Tollerson, R and Witzky, A and Ibba, M}, title = {Elongation factor P is required to maintain proteome homeostasis at high growth rate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11072-11077}, pmid = {30297417}, issn = {1091-6490}, support = {R01 GM065183/GM/NIGMS NIH HHS/United States ; T32 GM086252/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Escherichia coli/drug effects/*metabolism/*physiology ; Homeostasis/drug effects/*physiology ; Peptide Chain Elongation, Translational/physiology ; Peptide Elongation Factors/*metabolism ; Peptides/metabolism ; Phenotype ; Polyribosomes/metabolism ; Proteome/*metabolism ; Ribosomes/metabolism ; Virulence/physiology ; }, abstract = {Elongation factor P (EF-P) is a universally conserved translation factor that alleviates ribosome pausing at polyproline (PPX) motifs by facilitating peptide bond formation. In the absence of EF-P, PPX peptide bond formation can limit translation rate, leading to pleotropic phenotypes including slowed growth, increased antibiotic sensitivity, and loss of virulence. In this study, we observe that many of these phenotypes are dependent on growth rate. Limiting growth rate suppresses a variety of detrimental phenotypes associated with ribosome pausing at PPX motifs in the absence of EF-P. Polysome levels are also similar to wild-type under slow growth conditions, consistent with global changes in ribosome queuing in cells without EF-P when growth rate is decreased. Inversely, under high protein synthesis demands, we observe that Escherichia coli lacking EF-P have reduced fitness. Our data demonstrate that EF-P-mediated relief of ribosome queuing is required to maintain proteome homeostasis under conditions of high translational demands.}, } @article {pmid30297416, year = {2018}, author = {McKillop, H and Aoyama, K}, title = {Salt and marine products in the Classic Maya economy from use-wear study of stone tools.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10948-10952}, pmid = {30297416}, issn = {1091-6490}, mesh = {Animals ; Archaeology/*history ; Asian Continental Ancestry Group ; Belize ; Civilization/*history ; Fishes/*anatomy & histology ; History, Ancient ; Humans ; Meat/analysis ; Minority Groups ; Seafood/analysis ; Sodium Chloride/*chemistry ; Sodium Chloride, Dietary/*analysis ; }, abstract = {Microscopic study of the edges of Late to Terminal Classic Maya (AD 600-900) chert stone tools from the Paynes Creek Salt Works, Belize, indicates most tools were used for cutting fish or meat or working hide, which was unexpected, given the virtual absence of fish or other animal remains at this large salt-production complex. Use-wear study shows that a minority of stone tools have edge-wear from woodworking. Our study suggests that salting fish was a significant activity at the salt works, which corresponds to Roman, Chinese, and other East Asian civilizations, where salt and salted fish were critical components of food storage, trade, and state finance. Based on analogy with modern Maya salt producers at Sacapulas, Guatemala, we provide estimates of the amounts of salt and salted fish produced at the Paynes Creek Salt Works and the implications for the Classic Maya economy. Salt cakes and salted fish were preserved commodities that could be stored and traded in the marketplace.}, } @article {pmid30297415, year = {2018}, author = {Raveendra, BL and Swarnkar, S and Avchalumov, Y and Liu, XA and Grinman, E and Badal, K and Reich, A and Pascal, BD and Puthanveettil, SV}, title = {Long noncoding RNA GM12371 acts as a transcriptional regulator of synapse function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10197-E10205}, pmid = {30297415}, issn = {1091-6490}, support = {R21 DA039417/DA/NIDA NIH HHS/United States ; R21 MH108929/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Female ; Gene Expression Regulation/*genetics ; Hippocampus/physiology ; Mice ; Neurons/physiology ; Pregnancy ; RNA, Long Noncoding/*genetics ; Signal Transduction/genetics ; Synapses/*genetics ; Transcription, Genetic/*genetics ; Up-Regulation/genetics ; }, abstract = {Despite the growing evidence suggesting that long noncoding RNAs (lncRNAs) are critical regulators of several biological processes, their functions in the nervous system remain elusive. We have identified an lncRNA, GM12371, in hippocampal neurons that is enriched in the nucleus and necessary for synaptic communication, synapse density, synapse morphology, and dendritic tree complexity. Mechanistically, GM12371 regulates the expression of several genes involved in neuronal development and differentiation, as well as expression of specific lncRNAs and their cognate mRNA targets. Furthermore, we find that cAMP-PKA signaling up-regulates the expression of GM12371 and that its expression is essential for the activity-dependent changes in synaptic transmission in hippocampal neurons. Taken together, our data establish a key role for GM12371 in regulating synapse function.}, } @article {pmid30297414, year = {2018}, author = {Spees, WM and Lin, TH and Sun, P and Song, C and George, A and Gary, SE and Yang, HC and Song, SK}, title = {MRI-based assessment of function and dysfunction in myelinated axons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10225-E10234}, pmid = {30297414}, issn = {1091-6490}, support = {P01 NS059560/NS/NINDS NIH HHS/United States ; R01 NS047592/NS/NINDS NIH HHS/United States ; U01 EY025500/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Anura ; Axons/*pathology ; Brain Mapping/methods ; Diffusion ; Diffusion Magnetic Resonance Imaging/methods ; Diffusion Tensor Imaging/methods ; Image Processing, Computer-Assisted/methods ; Myelin Sheath/*pathology ; Nerve Fibers, Myelinated/*pathology ; Sciatic Nerve/pathology ; }, abstract = {Repetitive electrical activity produces microstructural alteration in myelinated axons, which may afford the opportunity to noninvasively monitor function of myelinated fibers in peripheral nervous system (PNS)/CNS pathways. Microstructural changes were assessed via two different magnetic-resonance-based approaches: diffusion fMRI and dynamic T2 spectroscopy in the ex vivo perfused bullfrog sciatic nerves. Using this robust, classical model as a platform for testing, we demonstrate that noninvasive diffusion fMRI, based on standard diffusion tensor imaging (DTI), can clearly localize the sites of axonal conduction blockage as might be encountered in neurotrauma or other lesion types. It is also shown that the diffusion fMRI response is graded in proportion to the total number of electrical impulses carried through a given locus. Dynamic T2 spectroscopy of the perfused frog nerves point to an electrical-activity-induced redistribution of tissue water and myelin structural changes. Diffusion basis spectrum imaging (DBSI) reveals a reversible shift of tissue water into a restricted isotropic diffusion signal component. Submyelinic vacuoles are observed in electron-microscopy images of tissue fixed during electrical stimulation. A slowing of the compound action potential conduction velocity accompanies repetitive electrical activity. Correlations between electrophysiology and MRI parameters during and immediately after stimulation are presented. Potential mechanisms and interpretations of these results are discussed.}, } @article {pmid30297413, year = {2018}, author = {Liu, Z and Lemmonds, S and Huang, J and Tyagi, M and Hong, L and Jain, N}, title = {Entropic contribution to enhanced thermal stability in the thermostable P450 CYP119.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10049-E10058}, pmid = {30297413}, issn = {1091-6490}, mesh = {Archaeal Proteins/*metabolism ; Cytochrome P-450 Enzyme System/*metabolism ; Entropy ; Magnetic Resonance Spectroscopy/methods ; Protein Denaturation ; Sulfolobus acidocaldarius/metabolism ; Temperature ; Thermodynamics ; }, abstract = {The enhanced thermostability of thermophilic proteins with respect to their mesophilic counterparts is often attributed to the enthalpy effect, arising from strong interactions between protein residues. Intuitively, these strong interresidue interactions will rigidify the biomolecules. However, the present work utilizing neutron scattering and solution NMR spectroscopy measurements demonstrates a contrary example that the thermophilic cytochrome P450, CYP119, is much more flexible than its mesophilic counterpart, CYP101A1, something which is not apparent just from structural comparison of the two proteins. A mechanism to explain this apparent contradiction is that higher flexibility in the folded state of CYP119 increases its conformational entropy and thereby reduces the entropy gain during denaturation, which will increase the free energy needed for unfolding and thus stabilize the protein. This scenario is supported by thermodynamic data on the temperature dependence of unfolding free energy, which shows a significant entropic contribution to the thermostability of CYP119 and lends an added dimension to enhanced stability, previously attributed only to presence of aromatic stacking interactions and salt bridge networks. Our experimental data also support the notion that highly thermophilic P450s such as CYP119 may use a mechanism that partitions flexibility differently from mesophilic P450s between ligand binding and thermal stability.}, } @article {pmid30297412, year = {2018}, author = {Owen, RB and Muiruri, VM and Lowenstein, TK and Renaut, RW and Rabideaux, N and Luo, S and Deino, AL and Sier, MJ and Dupont-Nivet, G and McNulty, EP and Leet, K and Cohen, A and Campisano, C and Deocampo, D and Shen, CC and Billingsley, A and Mbuthia, A}, title = {Progressive aridification in East Africa over the last half million years and implications for human evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11174-11179}, pmid = {30297412}, issn = {1091-6490}, mesh = {Africa, Eastern ; Animals ; *Biological Evolution ; Climate Change ; *Cultural Evolution ; Fossils ; Geologic Sediments ; Hominidae/physiology ; Humans ; Kenya ; Lakes ; Mammals/physiology ; Paleontology/methods ; }, abstract = {Evidence for Quaternary climate change in East Africa has been derived from outcrops on land and lake cores and from marine dust, leaf wax, and pollen records. These data have previously been used to evaluate the impact of climate change on hominin evolution, but correlations have proved to be difficult, given poor data continuity and the great distances between marine cores and terrestrial basins where fossil evidence is located. Here, we present continental coring evidence for progressive aridification since about 575 thousand years before present (ka), based on Lake Magadi (Kenya) sediments. This long-term drying trend was interrupted by many wet-dry cycles, with the greatest variability developing during times of high eccentricity-modulated precession. Intense aridification apparent in the Magadi record took place between 525 and 400 ka, with relatively persistent arid conditions after 350 ka and through to the present. Arid conditions in the Magadi Basin coincide with the Mid-Brunhes Event and overlap with mammalian extinctions in the South Kenya Rift between 500 and 400 ka. The 525 to 400 ka arid phase developed in the South Kenya Rift between the period when the last Acheulean tools are reported (at about 500 ka) and before the appearance of Middle Stone Age artifacts (by about 320 ka). Our data suggest that increasing Middle- to Late-Pleistocene aridification and environmental variability may have been drivers in the physical and cultural evolution of Homo sapiens in East Africa.}, } @article {pmid30297411, year = {2018}, author = {Nour, MM and Dahoun, T and Schwartenbeck, P and Adams, RA and FitzGerald, THB and Coello, C and Wall, MB and Dolan, RJ and Howes, OD}, title = {Dopaminergic basis for signaling belief updates, but not surprise, and the link to paranoia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10167-E10176}, pmid = {30297411}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MC-A656-5QD30//Medical Research Council/United Kingdom ; 094849/Z/10/Z//Wellcome Trust/United Kingdom ; 098362/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Bayes Theorem ; Brain/physiopathology ; Brain Mapping/methods ; Culture ; Dopamine/*metabolism ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Motivation/*physiology ; Paranoid Disorders/*metabolism/*physiopathology ; Psychotic Disorders/*metabolism/*physiopathology ; Receptors, Dopamine/metabolism ; }, abstract = {Distinguishing between meaningful and meaningless sensory information is fundamental to forming accurate representations of the world. Dopamine is thought to play a central role in processing the meaningful information content of observations, which motivates an agent to update their beliefs about the environment. However, direct evidence for dopamine's role in human belief updating is lacking. We addressed this question in healthy volunteers who performed a model-based fMRI task designed to separate the neural processing of meaningful and meaningless sensory information. We modeled participant behavior using a normative Bayesian observer model and used the magnitude of the model-derived belief update following an observation to quantify its meaningful information content. We also acquired PET imaging measures of dopamine function in the same subjects. We show that the magnitude of belief updates about task structure (meaningful information), but not pure sensory surprise (meaningless information), are encoded in midbrain and ventral striatum activity. Using PET we show that the neural encoding of meaningful information is negatively related to dopamine-2/3 receptor availability in the midbrain and dexamphetamine-induced dopamine release capacity in the striatum. Trial-by-trial analysis of task performance indicated that subclinical paranoid ideation is negatively related to behavioral sensitivity to observations carrying meaningful information about the task structure. The findings provide direct evidence implicating dopamine in model-based belief updating in humans and have implications for understating the pathophysiology of psychotic disorders where dopamine function is disrupted.}, } @article {pmid30297410, year = {2018}, author = {}, title = {Correction for Lee et al., Altered ER-mitochondria contact impacts mitochondria calcium homeostasis and contributes to neurodegeneration in vivo in disease models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9992}, doi = {10.1073/pnas.1815900115}, pmid = {30297410}, issn = {1091-6490}, } @article {pmid30297409, year = {2018}, author = {Kim, JH and Gangadharan, G and Byun, J and Choi, EJ and Lee, CJ and Shin, HS}, title = {Yin-and-yang bifurcation of opioidergic circuits for descending analgesia at the midbrain of the mouse.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11078-11083}, pmid = {30297409}, issn = {1091-6490}, mesh = {Analgesia/*methods ; Analgesics, Opioid/pharmacology ; Animals ; Male ; Mesencephalon/drug effects/*physiopathology ; Mice ; Mice, Inbred C57BL ; Morphine/pharmacology ; Neural Pathways/drug effects/physiology ; Neurons/drug effects/physiology ; Pain/physiopathology ; Pain Management/*methods ; Spinal Cord/drug effects/physiology ; Yin-Yang ; }, abstract = {In the descending analgesia pathway, opioids are known to disinhibit the projections from the periaqueductal gray (PAG) to the rostral ventromedial medulla (RVM), leading to suppression of pain signals at the spinal cord level. The locus coeruleus (LC) has been proposed to engage in the descending pathway through noradrenergic inputs to the spinal cord. Nevertheless, how the LC is integrated in the descending analgesia circuit has remained unknown. Here, we show that the opioidergic analgesia pathway is bifurcated in structure and function at the PAG. A knockout as well as a PAG-specific knockdown of phospholipase C β4 (PLCβ4), a signaling molecule for G protein-coupled receptors, enhanced swim stress-induced and morphine-induced analgesia in mice. Immunostaining after simultaneous retrograde labeling from the RVM and the LC revealed two mutually exclusive neuronal populations at the PAG, each projecting either to the LC or the RVM, with PLCβ4 expression only in the PAG-LC projecting cells that provide a direct synaptic input to LC-spinal cord (SC) projection neurons. The PAG-LC projection neurons in wild-type mice turned quiescent in response to opiates, but remained active in the PLCβ4 mutant, suggesting a possibility that an increased adrenergic function induced by the persistent PAG-LC activity underlies the enhanced opioid analgesia in the mutant. Indeed, the enhanced analgesia in the mutant was reversed by blocking α2-noradrenergic receptors. These findings indicate that opioids suppress descending analgesia through the PAG-LC pathway, while enhancing it through the PAG-RVM pathway, i.e., two distinct pathways with opposing effects on opioid analgesia. These results point to a therapeutic target in pain control.}, } @article {pmid30297408, year = {2018}, author = {Wada, M and Lokugamage, KG and Nakagawa, K and Narayanan, K and Makino, S}, title = {Interplay between coronavirus, a cytoplasmic RNA virus, and nonsense-mediated mRNA decay pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10157-E10166}, pmid = {30297408}, issn = {1091-6490}, support = {R01 AI099107/AI/NIAID NIH HHS/United States ; R01 AI114657/AI/NIAID NIH HHS/United States ; }, mesh = {3' Untranslated Regions/genetics ; Animals ; Coronavirus/*genetics ; Cytoplasm/*genetics ; Mice ; Nonsense Mediated mRNA Decay/*genetics ; Open Reading Frames/genetics ; RNA Stability/*genetics ; RNA Viruses/*genetics ; RNA, Messenger/*genetics ; Virus Replication/genetics ; }, abstract = {Coronaviruses (CoVs), including severe acute respiratory syndrome CoV and Middle East respiratory syndrome CoV, are enveloped RNA viruses that carry a large positive-sense single-stranded RNA genome and cause a variety of diseases in humans and domestic animals. Very little is known about the host pathways that regulate the stability of CoV mRNAs, which carry some unusual features. Nonsense-mediated decay (NMD) is a eukaryotic RNA surveillance pathway that detects mRNAs harboring aberrant features and targets them for degradation. Although CoV mRNAs are of cytoplasmic origin, the presence of several NMD-inducing features (including multiple ORFs with internal termination codons that create a long 3' untranslated region) in CoV mRNAs led us to explore the interplay between the NMD pathway and CoVs. Our study using murine hepatitis virus as a model CoV showed that CoV mRNAs are recognized by the NMD pathway as a substrate, resulting in their degradation. Furthermore, CoV replication induced the inhibition of the NMD pathway, and N protein (a viral structural protein) had an NMD inhibitory function that protected viral mRNAs from rapid decay. Our data further suggest that the NMD pathway interferes with optimal viral replication by degrading viral mRNAs early in infection, before sufficient accumulation of N protein. Our study presents clear evidence for the biological importance of the NMD pathway in controlling the stability of mRNAs and the efficiency of replication of a cytoplasmic RNA virus.}, } @article {pmid30297407, year = {2018}, author = {Scanlan, MM and Putman, NF and Pollock, AM and Noakes, DLG}, title = {Magnetic map in nonanadromous Atlantic salmon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10995-10999}, pmid = {30297407}, issn = {1091-6490}, mesh = {Animal Migration/physiology ; Animals ; Aquaculture/methods ; Magnetics/methods ; Maine ; Oregon ; Pacific Ocean ; Salmo salar/*physiology ; }, abstract = {Long-distance migrants, including Pacific salmon (Oncorhynchus spp), can use geomagnetic information to navigate. We tested the hypothesis that a "magnetic map" (i.e., an ability to extract positional information from Earth's magnetic field) also exists in a population of salmon that do not undertake oceanic migrations. This study examined juvenile Atlantic salmon (Salmo salar) originally from a nonanadromous population in Maine transferred ∼60 years ago to a lake in central Oregon. We exposed juveniles to magnetic displacements representative of locations at the latitudinal boundaries of the Pacific salmon oceanic range in the North Pacific and at the periphery of their ancestral oceanic range in the North Atlantic. Orientation differed among the magnetic treatments, indicating that Atlantic salmon detect map information from the geomagnetic field. Despite no recent history of ocean migration, these fish displayed adaptive orientation responses similar to those observed in native Pacific salmonids. These findings indicate that use of map information from the geomagnetic field is a shared ancestral character in the family Salmonidae and is not restricted to populations with anadromous life histories. Lastly, given that Atlantic salmon are transported throughout the world for capture fisheries and aquaculture, such a robust navigational system is of some concern. Escaped individuals may have greater potential to successfully navigate, and thus invade, introduced habitats than previously suspected.}, } @article {pmid30297406, year = {2018}, author = {Tavares, H and Whibley, A and Field, DL and Bradley, D and Couchman, M and Copsey, L and Elleouet, J and Burrus, M and Andalo, C and Li, M and Li, Q and Xue, Y and Rebocho, AB and Barton, NH and Coen, E}, title = {Selection and gene flow shape genomic islands that control floral guides.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11006-11011}, pmid = {30297406}, issn = {1091-6490}, support = {BBS/E/J/000PR9773//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/G009325/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Antirrhinum/genetics ; Chromosomes, Plant/genetics ; Color ; Flowers/*genetics ; Gene Flow/*genetics ; Genetic Speciation ; Genome, Plant/genetics ; Genomic Islands/*genetics ; Selection, Genetic/*genetics ; }, abstract = {Genomes of closely-related species or populations often display localized regions of enhanced relative sequence divergence, termed genomic islands. It has been proposed that these islands arise through selective sweeps and/or barriers to gene flow. Here, we genetically dissect a genomic island that controls flower color pattern differences between two subspecies of Antirrhinum majus, A.m.striatum and A.m.pseudomajus, and relate it to clinal variation across a natural hybrid zone. We show that selective sweeps likely raised relative divergence at two tightly-linked MYB-like transcription factors, leading to distinct flower patterns in the two subspecies. The two patterns provide alternate floral guides and create a strong barrier to gene flow where populations come into contact. This barrier affects the selected flower color genes and tightly-linked loci, but does not extend outside of this domain, allowing gene flow to lower relative divergence for the rest of the chromosome. Thus, both selective sweeps and barriers to gene flow play a role in shaping genomic islands: sweeps cause elevation in relative divergence, while heterogeneous gene flow flattens the surrounding "sea," making the island of divergence stand out. By showing how selective sweeps establish alternative adaptive phenotypes that lead to barriers to gene flow, our study sheds light on possible mechanisms leading to reproductive isolation and speciation.}, } @article {pmid30297405, year = {2018}, author = {}, title = {Correction for Sanchez et al., Near-term deployment of carbon capture and sequestration from biorefineries in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9991}, doi = {10.1073/pnas.1816158115}, pmid = {30297405}, issn = {1091-6490}, } @article {pmid30297404, year = {2018}, author = {Xu, R and Xu, Y and Huo, W and Lv, Z and Yuan, J and Ning, S and Wang, Q and Hou, M and Gao, G and Ji, J and Chen, J and Guo, R and Xu, D}, title = {Mitosis-specific MRN complex promotes a mitotic signaling cascade to regulate spindle dynamics and chromosome segregation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10079-E10088}, pmid = {30297404}, issn = {1091-6490}, mesh = {Cell Cycle Proteins/metabolism ; Cell Line ; Cell Line, Tumor ; Chromosome Segregation/*physiology ; DNA-Binding Proteins/*metabolism ; HCT116 Cells ; HEK293 Cells ; HeLa Cells ; Humans ; Kinesin/metabolism ; MRE11 Homologue Protein/*metabolism ; Microtubules/metabolism ; Mitosis/*physiology ; Nuclear Proteins/*metabolism ; Phosphorylation/physiology ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins/metabolism ; Spindle Apparatus/metabolism/*physiology ; }, abstract = {The MRE11-RAD50-NBS1 (MRN) complex is well known for participating in DNA damage response pathways in all phases of cell cycle. Here, we show that MRN constitutes a mitosis-specific complex, named mMRN, with a protein, MMAP. MMAP directly interacts with MRE11 and is required for optimal stability of the MRN complex during mitosis. MMAP colocalizes with MRN in mitotic spindles, and MMAP-deficient cells display abnormal spindle dynamics and chromosome segregation similar to MRN-deficient cells. Mechanistically, both MMAP and MRE11 are hyperphosphorylated by the mitotic kinase, PLK1; and the phosphorylation is required for assembly of the mMRN complex. The assembled mMRN complex enables PLK1 to interact with and activate the microtubule depolymerase, KIF2A, leading to spindle turnover and chromosome segregation. Our study identifies a mitosis-specific version of the MRN complex that acts in the PLK1-KIF2A signaling cascade to regulate spindle dynamics and chromosome distribution.}, } @article {pmid30297403, year = {2018}, author = {García, FC and Bestion, E and Warfield, R and Yvon-Durocher, G}, title = {Changes in temperature alter the relationship between biodiversity and ecosystem functioning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10989-10994}, pmid = {30297403}, issn = {1091-6490}, mesh = {*Biodiversity ; Biomass ; *Ecosystem ; Introduced Species ; Models, Biological ; Temperature ; }, abstract = {Global warming and the loss of biodiversity through human activities (e.g., land-use change, pollution, invasive species) are two of the most profound threats to the functional integrity of the Earth's ecosystems. These factors are, however, most frequently investigated separately, ignoring the potential for synergistic effects of biodiversity loss and environmental warming on ecosystem functioning. Here we use high-throughput experiments with microbial communities to investigate how changes in temperature affect the relationship between biodiversity and ecosystem functioning. We found that changes in temperature systematically altered the relationship between biodiversity and ecosystem functioning. As temperatures departed from ambient conditions the exponent of the diversity-functioning relationship increased, meaning that more species were required to maintain ecosystem functioning under thermal stress. This key result was driven by two processes linked to variability in the thermal tolerance curves of taxa. First, more diverse communities had a greater chance of including species with thermal traits that enabled them to maintain productivity as temperatures shifted from ambient conditions. Second, we found a pronounced increase in the contribution of complementarity to the net biodiversity effect at high and low temperatures, indicating that changes in species interactions played a critical role in mediating the impacts of temperature change on the relationship between biodiversity and ecosystem functioning. Our results highlight that if biodiversity loss occurs independently of species' thermal tolerance traits, then the additional impacts of environmental warming will result in sharp declines in ecosystem function.}, } @article {pmid30297402, year = {2018}, author = {Krause, DJ and Kominek, J and Opulente, DA and Shen, XX and Zhou, X and Langdon, QK and DeVirgilio, J and Hulfachor, AB and Kurtzman, CP and Rokas, A and Hittinger, CT}, title = {Functional and evolutionary characterization of a secondary metabolite gene cluster in budding yeasts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11030-11035}, pmid = {30297402}, issn = {1091-6490}, support = {T32 GM007133/GM/NIGMS NIH HHS/United States ; }, mesh = {Iron/metabolism ; Kluyveromyces/genetics ; Membrane Transport Proteins/genetics ; Multigene Family/*genetics ; Phylogeny ; Protein Biosynthesis/genetics ; Saccharomyces cerevisiae/genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; Saccharomycetales/*genetics/metabolism ; Secondary Metabolism/*genetics ; Siderophores/genetics ; Transcription Factors/genetics ; }, abstract = {Secondary metabolites are key in how organisms from all domains of life interact with their environment and each other. The iron-binding molecule pulcherrimin was described a century ago, but the genes responsible for its production in budding yeasts have remained uncharacterized. Here, we used phylogenomic footprinting on 90 genomes across the budding yeast subphylum Saccharomycotina to identify the gene cluster associated with pulcherrimin production. Using targeted gene replacements in Kluyveromyces lactis, we characterized the four genes that make up the cluster, which likely encode two pulcherriminic acid biosynthesis enzymes, a pulcherrimin transporter, and a transcription factor involved in both biosynthesis and transport. The requirement of a functional putative transporter to utilize extracellular pulcherrimin-complexed iron demonstrates that pulcherriminic acid is a siderophore, a chelator that binds iron outside the cell for subsequent uptake. Surprisingly, we identified homologs of the putative transporter and transcription factor genes in multiple yeast genera that lacked the biosynthesis genes and could not make pulcherrimin, including the model yeast Saccharomyces cerevisiae We deleted these previously uncharacterized genes and showed they are also required for pulcherrimin utilization in S. cerevisiae, raising the possibility that other genes of unknown function are linked to secondary metabolism. Phylogenetic analyses of this gene cluster suggest that pulcherrimin biosynthesis and utilization were ancestral to budding yeasts, but the biosynthesis genes and, subsequently, the utilization genes, were lost in many lineages, mirroring other microbial public goods systems that lead to the rise of cheater organisms.}, } @article {pmid30297401, year = {2018}, author = {}, title = {Correction for CaraDonna et al., Shifts in flowering phenology reshape a subalpine plant community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9993}, doi = {10.1073/pnas.1815637115}, pmid = {30297401}, issn = {1091-6490}, } @article {pmid30297400, year = {2018}, author = {Jonker, TR and Dimsdale-Zucker, H and Ritchey, M and Clarke, A and Ranganath, C}, title = {Neural reactivation in parietal cortex enhances memory for episodically linked information.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11084-11089}, pmid = {30297400}, issn = {1091-6490}, mesh = {Brain Mapping/methods ; Female ; Hippocampus/physiology ; Humans ; Image Processing, Computer-Assisted/methods ; Magnetic Resonance Imaging/methods ; Male ; Memory, Episodic ; Mental Recall/*physiology ; Nerve Net/*physiology ; Parietal Lobe/*physiology ; Reaction Time/physiology ; Temporal Lobe/physiology ; }, abstract = {Remembering is a complex process that involves recalling specific details, such as who you were with when you celebrated your last birthday, as well as contextual information, such as the place where you celebrated. It is well established that the act of remembering enhances long-term retention of the retrieved information, but the neural and cognitive mechanisms that drive memory enhancement are not yet understood. One possibility is that the process of remembering results in reactivation of the broader episodic context. Consistent with this idea, in two experiments, we found that multiple retrieval attempts enhanced long-term retention of both the retrieved object and the nontarget object that shared scene context, compared with a restudy control. Using representational similarity analysis of fMRI data in experiment 2, we found that retrieval resulted in greater neural reactivation of both the target objects and contextually linked objects compared with restudy. Furthermore, this reactivation occurred in a network of medial and lateral parietal lobe regions that have been linked to episodic recollection. The results demonstrate that retrieving a memory can enhance retention of information that is linked in the broader event context and the hippocampus and a posterior medial network of parietal cortical areas (also known as the Default Network) play complementary roles in supporting the reactivation of episodically linked information during retrieval.}, } @article {pmid30297399, year = {2018}, author = {Amoroso, RO and Pitcher, CR and Rijnsdorp, AD and McConnaughey, RA and Parma, AM and Suuronen, P and Eigaard, OR and Bastardie, F and Hintzen, NT and Althaus, F and Baird, SJ and Black, J and Buhl-Mortensen, L and Campbell, AB and Catarino, R and Collie, J and Cowan, JH and Durholtz, D and Engstrom, N and Fairweather, TP and Fock, HO and Ford, R and Gálvez, PA and Gerritsen, H and Góngora, ME and González, JA and Hiddink, JG and Hughes, KM and Intelmann, SS and Jenkins, C and Jonsson, P and Kainge, P and Kangas, M and Kathena, JN and Kavadas, S and Leslie, RW and Lewis, SG and Lundy, M and Makin, D and Martin, J and Mazor, T and Gonzalez-Mirelis, G and Newman, SJ and Papadopoulou, N and Posen, PE and Rochester, W and Russo, T and Sala, A and Semmens, JM and Silva, C and Tsolos, A and Vanelslander, B and Wakefield, CB and Wood, BA and Hilborn, R and Kaiser, MJ and Jennings, S}, title = {Bottom trawl fishing footprints on the world's continental shelves.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10275-E10282}, pmid = {30297399}, issn = {1091-6490}, mesh = {Alaska ; Animals ; Australia ; Biodiversity ; Chile ; Ecosystem ; Fisheries/*statistics & numerical data ; Invertebrates/physiology ; New Zealand ; Oceans and Seas ; Seafood/statistics & numerical data ; }, abstract = {Bottom trawlers land around 19 million tons of fish and invertebrates annually, almost one-quarter of wild marine landings. The extent of bottom trawling footprint (seabed area trawled at least once in a specified region and time period) is often contested but poorly described. We quantify footprints using high-resolution satellite vessel monitoring system (VMS) and logbook data on 24 continental shelves and slopes to 1,000-m depth over at least 2 years. Trawling footprint varied markedly among regions: from <10% of seabed area in Australian and New Zealand waters, the Aleutian Islands, East Bering Sea, South Chile, and Gulf of Alaska to >50% in some European seas. Overall, 14% of the 7.8 million-km2 study area was trawled, and 86% was not trawled. Trawling activity was aggregated; the most intensively trawled areas accounting for 90% of activity comprised 77% of footprint on average. Regional swept area ratio (SAR; ratio of total swept area trawled annually to total area of region, a metric of trawling intensity) and footprint area were related, providing an approach to estimate regional trawling footprints when high-resolution spatial data are unavailable. If SAR was ≤0.1, as in 8 of 24 regions, there was >95% probability that >90% of seabed was not trawled. If SAR was 7.9, equal to the highest SAR recorded, there was >95% probability that >70% of seabed was trawled. Footprints were smaller and SAR was ≤0.25 in regions where fishing rates consistently met international sustainability benchmarks for fish stocks, implying collateral environmental benefits from sustainable fishing.}, } @article {pmid30297398, year = {2018}, author = {Sossi, PA and Moynier, F and van Zuilen, K}, title = {Volatile loss following cooling and accretion of the Moon revealed by chromium isotopes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10920-10925}, pmid = {30297398}, issn = {1091-6490}, abstract = {Terrestrial and lunar rocks share chemical and isotopic similarities in refractory elements, suggestive of a common precursor. By contrast, the marked depletion of volatile elements in lunar rocks together with their enrichment in heavy isotopes compared with Earth's mantle suggests that the Moon underwent evaporative loss of volatiles. However, whether equilibrium prevailed during evaporation and, if so, at what conditions (temperature, pressure, and oxygen fugacity) remain unconstrained. Chromium may shed light on this question, as it has several thermodynamically stable, oxidized gas species that can distinguish between kinetic and equilibrium regimes. Here, we present high-precision Cr isotope measurements in terrestrial and lunar rocks that reveal an enrichment in the lighter isotopes of Cr in the Moon compared with Earth's mantle by 100 ± 40 ppm per atomic mass unit. This observation is consistent with Cr partitioning into an oxygen-rich vapor phase in equilibrium with the proto-Moon, thereby stabilizing the CrO2 species that is isotopically heavy compared with CrO in a lunar melt. Temperatures of 1,600-1,800 K and oxygen fugacities near the fayalite-magnetite-quartz buffer are required to explain the elemental and isotopic difference of Cr between Earth's mantle and the Moon. These temperatures are far lower than modeled in the aftermath of a giant impact, implying that volatile loss did not occur contemporaneously with impact but following cooling and accretion of the Moon.}, } @article {pmid30297397, year = {2018}, author = {Kowanetz, M and Zou, W and Gettinger, SN and Koeppen, H and Kockx, M and Schmid, P and Kadel, EE and Wistuba, I and Chaft, J and Rizvi, NA and Spigel, DR and Spira, A and Hirsch, FR and Cohen, V and Smith, D and Boyd, Z and Miley, N and Flynn, S and Leveque, V and Shames, DS and Ballinger, M and Mocci, S and Shankar, G and Funke, R and Hampton, G and Sandler, A and Amler, L and Mellman, I and Chen, DS and Hegde, PS}, title = {Differential regulation of PD-L1 expression by immune and tumor cells in NSCLC and the response to treatment with atezolizumab (anti-PD-L1).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10119-E10126}, pmid = {30297397}, issn = {1091-6490}, mesh = {Antibodies, Monoclonal/*therapeutic use ; B7-H1 Antigen/*immunology ; Carcinoma, Non-Small-Cell Lung/*immunology ; Humans ; Immunohistochemistry/methods ; Lung Neoplasms/drug therapy/*immunology ; Lymphocytes, Tumor-Infiltrating/drug effects ; Male ; Middle Aged ; T-Lymphocytes/drug effects/immunology ; }, abstract = {Programmed death-ligand 1 (PD-L1) expression on tumor cells (TCs) by immunohistochemistry is rapidly gaining importance as a diagnostic for the selection or stratification of patients with non-small cell lung cancer (NSCLC) most likely to respond to single-agent checkpoint inhibitors. However, at least two distinct patterns of PD-L1 expression have been observed with potential biological and clinical relevance in NSCLC: expression on TC or on tumor-infiltrating immune cells (ICs). We investigated the molecular and cellular characteristics associated with PD-L1 expression in these distinct cell compartments in 4,549 cases of NSCLC. PD-L1 expression on IC was more prevalent and likely reflected IFN-γ-induced adaptive regulation accompanied by increased tumor-infiltrating lymphocytes and effector T cells. High PD-L1 expression on TC, however, reflected an epigenetic dysregulation of the PD-L1 gene and was associated with a distinct histology described by poor immune infiltration, sclerotic/desmoplastic stroma, and mesenchymal molecular features. Importantly, durable clinical responses to atezolizumab (anti-PD-L1) were observed in patients with tumors expressing high PD-L1 levels on either TC alone [40% objective response rate (ORR)] or IC alone (22% ORR). Thus, PD-L1 expression on TC or IC can independently attenuate anticancer immunity and emphasizes the functional importance of IC in regulating the antitumor T cell response.}, } @article {pmid30297396, year = {2018}, author = {Wang, R and Li, Y and Tsung, A and Huang, H and Du, Q and Yang, M and Deng, M and Xiong, S and Wang, X and Zhang, L and Geller, DA and Cheng, B and Billiar, TR}, title = {iNOS promotes CD24+CD133+ liver cancer stem cell phenotype through a TACE/ADAM17-dependent Notch signaling pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10127-E10136}, pmid = {30297396}, issn = {1091-6490}, support = {R01 GM044100/GM/NIGMS NIH HHS/United States ; }, mesh = {AC133 Antigen/*metabolism ; ADAM17 Protein/*metabolism ; Biomarkers, Tumor/metabolism ; CD24 Antigen/*metabolism ; Cell Line, Tumor ; Female ; Humans ; Liver Neoplasms/*metabolism/pathology ; Male ; Middle Aged ; Neoplastic Stem Cells/*metabolism/pathology ; Nitric Oxide Synthase Type II/*metabolism ; Phenotype ; Receptors, Notch/*metabolism ; Signal Transduction/physiology ; Up-Regulation/physiology ; }, abstract = {The inducible nitric oxide synthase (iNOS) is associated with more aggressive solid tumors, including hepatocellular carcinoma (HCC). Notch signaling in cancer stem cells promotes cancer progression and requires Notch cleavage by ADAM (a disintegrin and metalloprotease) proteases. We hypothesized that iNOS/NO promotes Notch1 activation through TACE/ADAM17 activation in liver cancer stem cells (LCSCs), leading to a more aggressive cancer phenotype. Expression of the stem cell markers CD24 and CD133 in the tumors of patients with HCC was associated with greater iNOS expression and worse outcomes. The expression of iNOS in CD24+CD133+ LCSCs, but not CD24-CD133- LCSCs, promoted Notch1 signaling and stemness characteristics in vitro and in vivo, as well as accelerating HCC initiation and tumor formation in the mouse xenograft tumor model. iNOS/NO led to Notch1 signaling through a pathway involving the soluble guanylyl cyclase/cGMP/PKG-dependent activation of TACE/ADAM17 and up-regulation of iRhom2 in LCSCs. In patients with HCC, higher TACE/ADAM17 expression and Notch1 activation correlated with poor prognosis. These findings link iNOS to Notch1 signaling in CD24+CD133+ LCSCs through the activation of TACE/ADAM17 and identify a mechanism for how iNOS contributes to progression of CD24+CD133+ HCC.}, } @article {pmid30297395, year = {2018}, author = {Chan, LC and Rossetti, M and Miller, LS and Filler, SG and Johnson, CW and Lee, HK and Wang, H and Gjertson, D and Fowler, VG and Reed, EF and Yeaman, MR and , }, title = {Protective immunity in recurrent Staphylococcus aureus infection reflects localized immune signatures and macrophage-conferred memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {47}, pages = {E11111-E11119}, pmid = {30297395}, issn = {1091-6490}, support = {R01 AR069502/AR/NIAMS NIH HHS/United States ; U01 AI124319/AI/NIAID NIH HHS/United States ; R21 AI126896/AI/NIAID NIH HHS/United States ; R33 AI111661/AI/NIAID NIH HHS/United States ; }, mesh = {Adoptive Transfer ; Animals ; Chemokine CCL5/blood ; Chemokine CXCL10/blood ; Dendritic Cells/immunology ; Disease Models, Animal ; Homeodomain Proteins/genetics ; Immunity, Innate/*immunology ; Immunologic Memory/*immunology ; Interferon-gamma/blood ; Interleukin-17/blood ; Interleukin-6/blood ; Macrophages/*immunology/*transplantation ; Male ; Methicillin-Resistant Staphylococcus aureus/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Staphylococcal Skin Infections/*immunology/microbiology ; Th17 Cells/immunology ; }, abstract = {Staphylococcus aureus is the leading cause of skin and skin structure infection (SSSI), a primary portal of entry for invasive infection. Our prior studies discovered a role for protective innate memory against recurrent methicillin-resistant S. aureus (MRSA) SSSI. In the present study, the dynamics and mechanisms of this response were explored in recurrent SSSI in WT mice. Priming by prior infection reduced skin lesion severity and MRSA burden, and protected against dissemination at day 7 but not day 2. Cytokine and cellular signatures in SSSI differed at day 2 versus 7, and were distinct in skin versus blood or spleen. Cytokines associated with protection in skin included increased IL-17, IL-6, monokine inducible by IFN-γ (MIG), and RANTES, while increased IP-10 correlated with protection from dissemination. Cellular signatures of protection included increased Th17, M1 macrophage, and dendritic cell populations in abscesses, and total macrophages in lymph nodes. Priming potentiated S. aureus-specific phagocytic killing by bone marrow-derived macrophages in vitro, and their adoptive transfer into naïve skin afforded protective efficacy in vivo. Present findings indicate that protective immunity in recurrent S. aureus infection is locally targeted, and involves specific memory conferred by macrophages. These insights provide targets for vaccine and immunotherapeutic development against MRSA.}, } @article {pmid30297394, year = {2018}, author = {Tilman, AR and Dixit, AK and Levin, SA}, title = {Localized prosocial preferences, public goods, and common-pool resources.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802872115}, pmid = {30297394}, issn = {1091-6490}, abstract = {The presence of prosocial preferences is thought to reduce significantly the difficulty of solving societal collective action problems such as providing public goods (or reducing public bads). However, prosociality is often limited to members of an in-group. We present a general theoretical model where society is split into subgroups and people care more about the welfare of others in their own subgroup than they do about those in out-groups. Individual contributions to the public good spill over and benefit members in each group to different degrees. We then consider special cases of our general model under which we can examine the consequences of localized prosociality for the economic outcomes of society as a whole. We ask to what extent prosociality closes the welfare gap between the Nash equilibrium without prosociality and the social optimum. The answer depends on whether private and public inputs are good or poor substitutes in producing final output. Critically, the degree to which this welfare gap closes is a concave function of the level of prosociality in the case of poor substitutes, so even low levels of prosociality can lead to social welfare near the social optimum.}, } @article {pmid30297393, year = {2018}, author = {Das, P and Veazey, KJ and Van, HT and Kaushik, S and Lin, K and Lu, Y and Ishii, M and Kikuta, J and Ge, K and Nussenzweig, A and Santos, MA}, title = {Histone methylation regulator PTIP is required to maintain normal and leukemic bone marrow niches.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10137-E10146}, pmid = {30297393}, issn = {1091-6490}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bone Marrow/*metabolism ; Bone Marrow Cells/metabolism ; Bone and Bones/metabolism ; Carrier Proteins/*metabolism ; Cell Differentiation/physiology ; Epigenesis, Genetic/physiology ; Hematopoiesis/physiology ; Hematopoietic Stem Cells/metabolism ; Histones/*metabolism ; Leukemia/*metabolism ; Methylation ; Mice ; Nuclear Proteins/*metabolism ; Osteoclasts/metabolism ; Osteogenesis/physiology ; PPAR gamma/metabolism ; Stem Cell Niche/*physiology ; }, abstract = {The bone is essential for locomotion, calcium storage, and harboring the hematopoietic stem cells (HSCs) that supply the body with mature blood cells throughout life. HSCs reside at the interface of the bone and bone marrow (BM), where active bone remodeling takes place. Although the cellular components of the BM niche have been characterized, little is known about its epigenetic regulation. Here we find that the histone methylation regulator PTIP (Pax interaction with transcription-activation domain protein-1) is required to maintain the integrity of the BM niche by promoting osteoclast differentiation. PTIP directly promotes chromatin changes required for the expression of Pparγ (peroxisome proliferator-activated receptor-γ), a transcription factor essential for osteoclastogenesis. PTIP deletion leads to a drastic reduction of HSCs in the BM and induces extramedullary hematopoiesis. Furthermore, exposure of acute myeloid leukemia cells to a PTIP-deficient BM microenvironment leads to a reduction in leukemia-initiating cells and increased survival upon transplantation. Taken together, our data identify PTIP as an epigenetic regulator of osteoclastogenesis that is required for the integrity of the BM niche to sustain both normal hematopoiesis and leukemia.}, } @article {pmid30297392, year = {2018}, author = {Robson, MJ and Quinlan, MA and Margolis, KG and Gajewski-Kurdziel, PA and Veenstra-VanderWeele, J and Gershon, MD and Watterson, DM and Blakely, RD}, title = {p38α MAPK signaling drives pharmacologically reversible brain and gastrointestinal phenotypes in the SERT Ala56 mouse.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10245-E10254}, pmid = {30297392}, issn = {1091-6490}, support = {P50 MH096972/MH/NIMH NIH HHS/United States ; R01 NS015547/NS/NINDS NIH HHS/United States ; K08 DK093786/DK/NIDDK NIH HHS/United States ; T32 NS007491/NS/NINDS NIH HHS/United States ; R01 MH094527/MH/NIMH NIH HHS/United States ; U01 AG043415/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/metabolism ; Brain/*metabolism ; Gastrointestinal Tract/*metabolism ; Male ; Mice ; Mitogen-Activated Protein Kinase 14/*metabolism ; Phenotype ; Receptors, Serotonin, 5-HT2/*metabolism ; Serotonin/*metabolism ; Serotonin Plasma Membrane Transport Proteins/*metabolism ; Signal Transduction/physiology ; }, abstract = {Autism spectrum disorder (ASD) is a common neurobehavioral disorder with limited treatment options. Activation of p38 MAPK signaling networks has been identified in ASD, and p38 MAPK signaling elevates serotonin (5-HT) transporter (SERT) activity, effects mimicked by multiple, hyperfunctional SERT coding variants identified in ASD subjects. Mice expressing the most common of these variants (SERT Ala56) exhibit hyperserotonemia, a biomarker observed in ASD subjects, as well as p38 MAPK-dependent SERT hyperphosphorylation, elevated hippocampal 5-HT clearance, hypersensitivity of CNS 5-HT1A and 5-HT2A/2C receptors, and behavioral and gastrointestinal perturbations reminiscent of ASD. As the α-isoform of p38 MAPK drives SERT activation, we tested the hypothesis that CNS-penetrant, α-isoform-specific p38 MAPK inhibitors might normalize SERT Ala56 phenotypes. Strikingly, 1-week treatment of adult SERT Ala56 mice with MW150, a selective p38α MAPK inhibitor, normalized hippocampal 5-HT clearance, CNS 5-HT1A and 5-HT2A/2C receptor sensitivities, social interactions, and colonic motility. Conditional elimination of p38α MAPK in 5-HT neurons of SERT Ala56 mice restored 5-HT1A and 5-HT2A/2C receptor sensitivities as well as social interactions, mirroring effects of MW150. Our findings support ongoing p38α MAPK activity as an important determinant of the physiological and behavioral perturbations of SERT Ala56 mice and, more broadly, supports consideration of p38α MAPK inhibition as a potential treatment for core and comorbid phenotypes present in ASD subjects.}, } @article {pmid30297391, year = {2018}, author = {Keiser, DA and Kling, CL and Shapiro, JS}, title = {The low but uncertain measured benefits of US water quality policy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802870115}, pmid = {30297391}, issn = {1091-6490}, abstract = {US investment to decrease pollution in rivers, lakes, and other surface waters has exceeded $1.9 trillion since 1960, and has also exceeded the cost of most other US environmental initiatives. These investments come both from the 1972 Clean Water Act and the largely voluntary efforts to control pollution from agriculture and urban runoff. This paper reviews the methods and conclusions of about 20 recent evaluations of these policies. Surprisingly, most analyses estimate that these policies' benefits are much smaller than their costs; the benefit-cost ratio from the median study is 0.37. However, existing evidence is limited and undercounts many types of benefits. We conclude that it is unclear whether many of these regulations truly fail a benefit-cost test or whether existing evidence understates their net benefits; we also describe specific questions that when answered would help eliminate this uncertainty.}, } @article {pmid30297245, year = {2018}, author = {Thompson, KA and Rieseberg, LH and Schluter, D}, title = {Speciation and the City.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {815-826}, doi = {10.1016/j.tree.2018.08.007}, pmid = {30297245}, issn = {1872-8383}, abstract = {Many outstanding questions about speciation are difficult to test empirically because of a lack of suitable study systems. Here, we highlight studies of evolutionary ecology in urban environments to argue that cities provide ideal conditions that can be leveraged to study the speciation process. Considering general findings from these studies, we discuss the mechanisms of speciation that are likely to occur in cities. We also discuss fundamental questions about speciation that urban environments are uniquely suited to address, such as those about the earliest stages of divergence or the role of phenotypic plasticity. We conclude that the study of contemporary speciation in urban environments has promise to facilitate discoveries about the process of speciation as it occurs in the Anthropocene.}, } @article {pmid30297157, year = {2018}, author = {van den Berg, H}, title = {A blooming and buzzing confusion: Buffon, Reimarus, and Kant on animal cognition.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {72}, number = {}, pages = {1-9}, doi = {10.1016/j.shpsc.2018.10.002}, pmid = {30297157}, issn = {1879-2499}, mesh = {Animals ; *Cognition ; History, 18th Century ; History, 19th Century ; Philosophy/*history ; }, abstract = {Kant's views on animals have received much attention in recent years. According to some, Kant attributed the capacity for objective perceptual awareness to non-human animals, even though he denied that they have concepts. This position is difficult to square with a conceptualist reading of Kant, according to which objective perceptual awareness requires concepts. Others take Kant's views on animals to imply that the mental life of animals is a blooming, buzzing confusion. In this article I provide a historical reconstruction of Kant's views on animals, relating them to eighteenth-century debates on animal cognition. I reconstruct the views of Buffon and Reimarus and show that (i) both Buffon and Reimarus adopted a conceptualist position, according to which concepts structure the cognitive experience of adult humans, and (ii) that both described the mental life of animals as a blooming, buzzing confusion. Kant's position, I argue, is virtually identical to that of Reimarus. Hence Kant's views on animals support a conceptualist reading of Kant. The article further articulates the historical antecedents of the Kantian idea that concepts structure human cognitive experience and provides a novel account of how the ideas of similarity and difference were conceptualized in eighteenth-century debates on animal cognition.}, } @article {pmid30297117, year = {2018}, author = {Sandhu, BK and McBride, SM}, title = {.Clostridioides difficile.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {1049-1050}, doi = {10.1016/j.tim.2018.09.004}, pmid = {30297117}, issn = {1878-4380}, abstract = {Clostridioides difficile is a spore-forming, anaerobic, intestinal pathogen that causes severe diarrhea that can lead to death. In 2011, C. difficile infected ∼500000 people in the USA and killed ∼29000 people. C. difficile infection (CDI) is the most common healthcare-related infection in the USA, leading to increased healthcare costs of $4.8 billion. This pathogen transmits via the oral-fecal route as a highly contagious and resilient spore. Upon exposure to primary bile acids in the intestine, C. difficile germinates, and in the absence of colonization resistance from the normal microbiota, the bacterium colonizes the colon and produces toxins. These toxins inhibit actin polymerization in host cells, leading to cell death. C. difficile cells can then sporulate in the intestine and exit the body via diarrheal shedding. In culture, sporulation is induced at stationary phase in a nutrient-limiting environment, but the intestinal triggers of sporulation are still unknown.}, } @article {pmid30296941, year = {2018}, author = {Kaplan, REW and Webster, AK and Chitrakar, R and Dent, JA and Baugh, LR}, title = {Food perception without ingestion leads to metabolic changes and irreversible developmental arrest in C. elegans.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {112}, pmid = {30296941}, issn = {1741-7007}, support = {T32 GM007754/GM/NIGMS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R01 GM117408/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Developmental physiology is very sensitive to nutrient availability. For instance, in the nematode Caenorhabditis elegans, newly hatched L1-stage larvae require food to initiate postembryonic development. In addition, larvae arrested in the dauer diapause, a non-feeding state of developmental arrest that occurs during the L3 stage, initiate recovery when exposed to food. Despite the essential role of food in C. elegans development, the contribution of food perception versus ingestion on physiology has not been delineated.

RESULTS: We used a pharmacological approach to uncouple the effects of food (bacteria) perception and ingestion in C. elegans. Perception was not sufficient to promote postembryonic development in L1-stage larvae. However, L1 larvae exposed to food without ingestion failed to develop upon return to normal culture conditions, instead displaying an irreversible arrest phenotype. Inhibition of gene expression during perception rescued subsequent development, demonstrating that the response to perception without feeding is deleterious. Perception altered DAF-16/FOXO subcellular localization, reflecting activation of insulin/IGF signaling (IIS). The insulin-like peptide daf-28 was specifically required, suggesting perception in chemosensory neurons, where it is expressed, regulates peptide synthesis and possibly secretion. However, genetic manipulation of IIS did not modify the irreversible arrest phenotype caused by food perception, revealing that wild-type function of the IIS pathway is not required to produce this phenotype and that other pathways affected by perception of food in the absence of its ingestion are likely to be involved. Gene expression and Nile red staining showed that food perception could alter lipid metabolism and storage. We found that starved larvae sense environmental polypeptides, with similar molecular and developmental effects as perception of bacteria. Environmental polypeptides also promoted recovery from dauer diapause, suggesting that perception of polypeptides plays an important role in the life history of free-living nematodes.

CONCLUSIONS: We conclude that actual ingestion of food is required to initiate postembryonic development in C. elegans. We also conclude that polypeptides are perceived as a food-associated cue in this and likely other animals, initiating a signaling and gene regulatory cascade that alters metabolism in anticipation of feeding and development, but that this response is detrimental if feeding does not occur.}, } @article {pmid30296849, year = {2018}, author = {Lassek, WD and Gaulin, SJC}, title = {Do the Low WHRs and BMIs Judged Most Attractive Indicate Better Health?.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918803998}, doi = {10.1177/1474704918803998}, pmid = {30296849}, issn = {1474-7049}, abstract = {It is widely claimed that in well-nourished populations, very low female waist-hip ratios (WHRs) together with low body mass indices (BMIs) are judged attractive by men because these features reliably indicate superior health and fertility. However, studies show that mortality rates are higher in women with low BMIs than in women with average BMIs and are inversely related to BMI in subsistence populations. Measures of current health in women of reproductive age have not been similarly studied. We analyze large U.S. samples of reproductive-age women and show that controlling for other factors known to affect health, those with low BMIs (<20), WHRs, or waist/stature ratios did not have better health than those with values in the middle range, and there was no relationship between subsequent health outcomes and BMI in early adulthood. Lower self-reported BMIs were linked to poorer health and an increased risk of infection. However, based on recent U.S. natality data, primiparas with lower BMIs had a lower risk of an operative delivery and of gestational hypertension. Beyond these two parity-restricted effects, relevant studies and new tests fail to support the view that women with the very low BMIs and WHRs consistently judged attractive are generally healthier than women with average values; significant correlations were consistently in the opposite direction.}, } @article {pmid30296846, year = {2018}, author = {Lassek, WD and Gaulin, SJC}, title = {Do the Low WHRs and BMIs Judged Most Attractive Indicate Higher Fertility?.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918800063}, doi = {10.1177/1474704918800063}, pmid = {30296846}, issn = {1474-7049}, abstract = {We examine the widely accepted view that very low waist-hip ratios and low body mass indices (BMIs) in women in well-nourished populations are judged attractive by men because these features reliably indicate superior fertility. In both subsistence and well-nourished populations, relevant studies of fertility do not support this view. Rather studies indicate lower fertility in women with anthropometric values associated with high attractiveness. Moreover, low maternal BMI predisposes to conditions that compromise infant survival. Consistent with these findings from the literature, new data from a large U.S. sample of women past reproductive age show that women with lower BMIs in the late teens had fewer live births, controlling for education, marital history, and race. They also had later menarche and earlier menopause compared with women with higher youth BMIs. In addition, data from the 2013 U.S. natality database show that mothers with lower prepregnancy BMIs have an increased risk of producing both low-birth-weight and preterm infants controlling for other relevant variables-conditions that would have adversely affected fitness over almost all of human evolution. Thus, a review of the relevant literature and three new tests fail to support the view that highly attractive women are more fertile.}, } @article {pmid30296393, year = {2018}, author = {Lehmann, R}, title = {Introduction: Challenges for Science: A Retrospective.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {v-viii}, doi = {10.1146/annurev-cb-34-030918-100001}, pmid = {30296393}, issn = {1530-8995}, } @article {pmid30296392, year = {2018}, author = {Mountoufaris, G and Canzio, D and Nwakeze, CL and Chen, WV and Maniatis, T}, title = {Writing, Reading, and Translating the Clustered Protocadherin Cell Surface Recognition Code for Neural Circuit Assembly.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {471-493}, doi = {10.1146/annurev-cellbio-100616-060701}, pmid = {30296392}, issn = {1530-8995}, abstract = {The ability of neurites of individual neurons to distinguish between themselves and neurites from other neurons and to avoid self (self-avoidance) plays a key role in neural circuit assembly in both invertebrates and vertebrates. Similarly, when individual neurons of the same type project into receptive fields of the brain, they must avoid each other to maximize target coverage (tiling). Counterintuitively, these processes are driven by highly specific homophilic interactions between cell surface proteins that lead to neurite repulsion rather than adhesion. Among these proteins in vertebrates are the clustered protocadherins (Pcdhs), and key to their function is the generation of enormous cell surface structural diversity. Here we review recent advances in understanding how a Pcdh cell surface code is generated by stochastic promoter choice; how this code is amplified and read by homophilic interactions between Pcdh complexes at the surface of neurons; and, finally, how the Pcdh code is translated to cellular function, which mediates self-avoidance and tiling and thus plays a central role in the development of complex neural circuits. Not surprisingly, Pcdh mutations that diminish homophilic interactions lead to wiring defects and abnormal behavior in mice, and sequence variants in the Pcdh gene cluster are associated with autism spectrum disorders in family-based genetic studies in humans.}, } @article {pmid30296391, year = {2018}, author = {Parton, RG}, title = {Caveolae: Structure, Function, and Relationship to Disease.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {111-136}, doi = {10.1146/annurev-cellbio-100617-062737}, pmid = {30296391}, issn = {1530-8995}, abstract = {The plasma membrane of eukaryotic cells is not a simple sheet of lipids and proteins but is differentiated into subdomains with crucial functions. Caveolae, small pits in the plasma membrane, are the most abundant surface subdomains of many mammalian cells. The cellular functions of caveolae have long remained obscure, but a new molecular understanding of caveola formation has led to insights into their workings. Caveolae are formed by the coordinated action of a number of lipid-interacting proteins to produce a microdomain with a specific structure and lipid composition. Caveolae can bud from the plasma membrane to form an endocytic vesicle or can flatten into the membrane to help cells withstand mechanical stress. The role of caveolae as mechanoprotective and signal transduction elements is reviewed in the context of disease conditions associated with caveola dysfunction.}, } @article {pmid30296390, year = {2018}, author = {Wagner, CE and Wheeler, KM and Ribbeck, K}, title = {Mucins and Their Role in Shaping the Functions of Mucus Barriers.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {189-215}, doi = {10.1146/annurev-cellbio-100617-062818}, pmid = {30296390}, issn = {1530-8995}, abstract = {We review what is currently understood about how the structure of the primary solid component of mucus, the glycoprotein mucin, gives rise to the mechanical and biochemical properties of mucus that are required for it to perform its diverse physiological roles. Macroscale processes such as lubrication require mucus of a certain stiffness and spinnability, which are set by structural features of the mucin network, including the identity and density of cross-links and the degree of glycosylation. At the microscale, these same features affect the mechanical environment experienced by small particles and play a crucial role in establishing an interaction-based filter. Finally, mucin glycans are critical for regulating microbial interactions, serving as receptor binding sites for adhesion, as nutrient sources, and as environmental signals. We conclude by discussing how these structural principles can be used in the design of synthetic mucin-mimetic materials and provide suggestions for directions of future work in this field.}, } @article {pmid30295866, year = {2018}, author = {Booker, TR and Keightley, PD}, title = {Understanding the Factors That Shape Patterns of Nucleotide Diversity in the House Mouse Genome.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2971-2988}, pmid = {30295866}, issn = {1537-1719}, abstract = {A major goal of population genetics has been to determine the extent by which selection at linked sites influences patterns of neutral nucleotide diversity in the genome. Multiple lines of evidence suggest that diversity is influenced by both positive and negative selection. For example, in many species there are troughs in diversity surrounding functional genomic elements, consistent with the action of either background selection (BGS) or selective sweeps. In this study, we investigated the causes of the diversity troughs that are observed in the wild house mouse genome. Using the unfolded site frequency spectrum, we estimated the strength and frequencies of deleterious and advantageous mutations occurring in different functional elements in the genome. We then used these estimates to parameterize forward-in-time simulations of chromosomes, using realistic distributions of functional elements and recombination rate variation in order to determine whether selection at linked sites can explain the observed patterns of nucleotide diversity. The simulations suggest that BGS alone cannot explain the dips in diversity around either exons or conserved noncoding elements. A combination of BGS and selective sweeps produces deeper dips in diversity than BGS alone, but the inferred parameters of selection cannot fully explain the patterns observed in the genome. Our results provide evidence of sweeps shaping patterns of nucleotide diversity across the mouse genome and also suggest that infrequent, strongly advantageous mutations play an important role in this. The limitations of using the unfolded site frequency spectrum for inferring the frequency and effects of advantageous mutations are discussed.}, } @article {pmid30294844, year = {2018}, author = {Raffard, A and Santoul, F and Cucherousset, J and Blanchet, S}, title = {The community and ecosystem consequences of intraspecific diversity: a meta-analysis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12472}, pmid = {30294844}, issn = {1469-185X}, abstract = {Understanding the relationships between biodiversity and ecosystem functioning has major implications. Biodiversity-ecosystem functioning relationships are generally investigated at the interspecific level, although intraspecific diversity (i.e. within-species diversity) is increasingly perceived as an important ecological facet of biodiversity. Here, we provide a quantitative and integrative synthesis testing, across diverse plant and animal species, whether intraspecific diversity is a major driver of community dynamics and ecosystem functioning. We specifically tested (i) whether the number of genotypes/phenotypes (i.e. intraspecific richness) or the specific identity of genotypes/phenotypes (i.e. intraspecific variation) in populations modulate the structure of communities and the functioning of ecosystems, (ii) whether the ecological effects of intraspecific richness and variation are strong in magnitude, and (iii) whether these effects vary among taxonomic groups and ecological responses. We found a non-linear relationship between intraspecific richness and community and ecosystem dynamics that follows a saturating curve shape, as observed for biodiversity-function relationships measured at the interspecific level. Importantly, intraspecific richness modulated ecological dynamics with a magnitude that was equal to that previously reported for interspecific richness. Our results further confirm, based on a database containing more than 50 species, that intraspecific variation also has substantial effects on ecological dynamics. We demonstrated that the effects of intraspecific variation are twice as high as expected by chance, and that they might have been underestimated previously. Finally, we found that the ecological effects of intraspecific variation are not homogeneous and are actually stronger when intraspecific variation is manipulated in primary producers than in consumer species, and when they are measured at the ecosystem rather than at the community level. Overall, we demonstrated that the two facets of intraspecific diversity (richness and variation) can both strongly affect community and ecosystem dynamics, which reveals the pivotal role of within-species biodiversity for understanding ecological dynamics.}, } @article {pmid30293695, year = {2018}, author = {Le Morvan, P}, title = {Searle on the biology of seeing.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {71}, number = {}, pages = {26-31}, doi = {10.1016/j.shpsc.2018.10.004}, pmid = {30293695}, issn = {1879-2499}, mesh = {Cognitive Science/*history ; *Consciousness ; History, 20th Century ; History, 21st Century ; *Vision, Ocular ; }, abstract = {Searle offers an account of seeing as a conscious state not constituted by the object(s) seen. I focus in this article on his biological case for this thesis, and argue that the biological considerations he adduces neither establish his own position nor defeat a rival object-inclusive view. I show (among other things) that taking seeing to be a biological state is compatible with its being (partially) constituted by the object(s) seen.}, } @article {pmid30293086, year = {2018}, author = {Du Toit, A}, title = {Shaping human evolution.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {717}, doi = {10.1038/s41579-018-0099-8}, pmid = {30293086}, issn = {1740-1534}, } @article {pmid30292786, year = {2018}, author = {López, SH and Avetisyan, M and Wright, CM and Mesbah, K and Kelly, RG and Moon, AM and Heuckeroth, RO}, title = {Loss of Tbx3 in murine neural crest reduces enteric glia and causes cleft palate, but does not influence heart development or bowel transit.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.09.017}, pmid = {30292786}, issn = {1095-564X}, support = {R01 DK087715/DK/NIDDK NIH HHS/United States ; }, abstract = {Transcription factors that coordinate migration, differentiation or proliferation of enteric nervous system (ENS) precursors are not well defined. To identify novel transcriptional regulators of ENS development, we performed microarray analysis at embryonic day (E) 17.5 and identified many genes that were enriched in the ENS compared to other bowel cells. We decided to investigate the T-box transcription factor Tbx3, which is prominently expressed in developing and mature ENS. Haploinsufficiency for TBX3 causes ulnar-mammary syndrome (UMS) in humans, a multi-organ system disorder. TBX3 also regulates several genes known to be important for ENS development. To test the hypothesis that Tbx3 is important for ENS development or function, we inactivated Tbx3 in all neural crest derivatives, including ENS progenitors using Wnt1-Cre and a floxed Tbx3 allele. Tbx3 fl/fl; Wnt1-Cre conditional mutant mice die shortly after birth with cleft palate and difficulty feeding. The ENS of mutants was well-organized with a normal density of enteric neurons and nerve fiber bundles, but small bowel glial cell density was reduced. Despite this, bowel motility appeared normal. Furthermore, although Tbx3 is expressed in cardiac neural crest, Tbx3 fl/fl; Wnt1-Cre mice had structurally normal hearts. Thus, loss of Tbx3 within neural crest has selective effects on Tbx3-expressing neural crest derivatives.}, } @article {pmid30292694, year = {2019}, author = {Fouquet, A and Ferrier, B and Salmona, J and Tirera, S and Vacher, JP and Courtois, EA and Gaucher, P and Lima, JD and Nunes, PMS and de Souza, SM and Rodrigues, MT and Noonan, B and de Thoisy, B}, title = {Phenotypic and life-history diversification in Amazonian frogs despite past introgressions.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {169-180}, doi = {10.1016/j.ympev.2018.09.010}, pmid = {30292694}, issn = {1095-9513}, abstract = {The advent of genomics in phylogenetics and population genetics strengthened the perception that conflicts among gene trees are frequent and often due to introgression. However, hybridization occurs mostly among species that exhibit little phenotypic differentiation. A recent study delineating species in Anomaloglossus, a frog genus endemic to the Guiana Shield, identified an intriguing pattern in the A. baeobatrachus species complex. This complex occurs in French Guiana and Amapá (Brazil) and comprises two sympatric phenotypes contrasting not only in body size, habitat, and advertisement call, but also in larval development mode (endotrophic vs exotrophic tadpoles). However, molecular and phenotypic divergences are, in some cases, incongruent, i.e specimens sharing mtDNA haplotypes are phenotypically distinct, suggesting a complex evolutionary history. Therefore, we genotyped 106 Anomaloglossus individuals using ddRADseq to test whether this phenotype/genotype incongruence was a product of phenotypic plasticity, incomplete lineage sorting, multiple speciation events, or admixture. Based on more than 16,000 SNPs, phylogenetic and population genetic approaches demonstrated that exotrophic populations are paraphyletic. Species tree and admixture analyses revealed a strikingly reticulate pattern, suggesting multiple historical introgression events. The evolutionary history of one exotrophic population in northern French Guiana is particularly compelling given that it received genetic material from exotrophic ancestors but shows very strong genetic affinity with the nearby endotrophic populations. This suggests strong selection on larval development and mating call after secondary contact and hybridization. The case of A. baeobatrachus represents a striking example of introgression among lineages that are phenotypically distinct, even in their larval development mode, and highlights how high-resolution genomic data can unravel unexpectedly complex evolutionary scenarios.}, } @article {pmid30292693, year = {2019}, author = {Tomasello, S and Stuessy, TF and Oberprieler, C and Heubl, G}, title = {Ragweeds and relatives: Molecular phylogenetics of Ambrosiinae (Asteraceae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {104-114}, doi = {10.1016/j.ympev.2018.10.005}, pmid = {30292693}, issn = {1095-9513}, abstract = {Ambrosiinae are one of the most distinct subtribes in the Heliantheae alliance (Asteraceae), mainly due to specialization toward wind pollination. Taxa of the subtribe are principally native to the Americas, although some species have attained a cosmopolitan distribution. Members of subtribe Engelmanniinae are considered close to Ambrosiinae, due to shared morphological traits. However, the placement of Ambrosiinae within the Heliantheae alliance has not yet been corroborated by phylogenetic analyses. In the present study, we test the circumscription of subtribe Ambrosiinae and examine relationships among its genera. We used sequence information from three plastid (psbA-trnH, trnQ-rps16 and trnL-F) and two nuclear (ITS and D35) marker regions. Phylogenetic inference analyses were conducted, applying Bayesian Inference (BI) and Maximum Likelihood (ML). Subtribe Ambrosiinae is found monophyletic or nearly so in all analyses. The genera Dugesia and Rojasianthe (previously considered part of subtribe Engelmanniinae) in some cases cluster together with Ambrosiinae; these genera are clearly not part of Engelmanniinae. Within Ambrosiinae, the genera Parthenium and Parthenice occupy basal positions, whereas members of the genus Ambrosia are the most derived representatives of the subtribe. Previous subdivision of Ambrosiinae into "Iveae" (members having androgynous capitula and free achenes) and "Ambrosieae" (genera with unisexual heads and achenes enclosed in burs) is not corroborated. Results also allow consideration of relationships among species and subgeneric groups within Parthenium, Iva, and Ambrosia.}, } @article {pmid30292647, year = {2018}, author = {Zeng, B and Lai, Z and Sun, L and Zhang, Z and Yang, J and Li, Z and Lin, J and Zhang, Z}, title = {Structural and functional profiles of the gut microbial community in polycystic ovary syndrome with insulin resistance (IR-PCOS): a pilot study.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.09.002}, pmid = {30292647}, issn = {1769-7123}, abstract = {Polycystic ovary syndrome (PCOS) is a complex endocrine and metabolic disorder that affects 9-21% of reproductive-aged women. Affected women frequently display obesity, insulin resistance, and inflammation. Altered gut microbial community has been reported in PCOS and obese PCOS patients. However, the profile of the gut microbial community in insulin resistant PCOS (IR-PCOS) patients still remains unknown. In this study, next-generation sequencing based on the 16S rRNA gene was used to compare the gut microbial composition of women with IR-PCOS (n = 9, PCOS with insulin resistance), NIR-PCOS (n = 8, PCOS alone) and healthy controls (n = 8, HC). We assessed that the composition of the gut microbial communities in NIR-PCOS and IR-PCOS patients were significantly altered. The family Bacteroidaceae was prolific in the NIR-PCOS group and reached its highest level in the IR-PCOS group, while the Prevotellaceae dramatically decreased in PCOS patients, especially in the IR-PCOS group. Subsequent correlation analysis revealed that the increased clinical parameter levels, including insulin resistance, sex-hormones and inflammation, were positively associated with the abundance of Bacteroidaceae, but negatively associated with that of Prevotellaceae. In addition, IR-PCOS patients also displayed a significant difference in their amounts of Ruminococcaceae and Lachnospiraceae when compared to the NIR-PCOS group. Moreover, the functional prediction from PICRUSt revealed that 73 pathways are significantly changed in the gut microbial communities of PCOS patients. Specifically, 21 metabolism-associated pathways, including the steroid hormone biosynthesis and lipopolysaccharide biosynthesis pathways, are obviously changed in IR-PCOS when compared to NIR-PCOS and HC groups. Taking this into consideration, our present study suggests that the dysbiosis of gut microbial communities occurred most notably in IR-PCOS patients, and the difference in gut dysbiosis profile between the IR-PCOS and NIR-PCOS should be considered in clinical treatment for PCOS patients and future drugs development.}, } @article {pmid30292640, year = {2018}, author = {Bick, AJ and Hapgood, JP}, title = {HIV-1 Latency Is Maintained by the Estrogen Receptor.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {891-892}, doi = {10.1016/j.tim.2018.09.005}, pmid = {30292640}, issn = {1878-4380}, abstract = {Persistence of the latent reservoir remains a challenge to curing HIV infection. Using shRNA screening, new insights into the molecular mechanisms underlying latency regulation indicate that the estrogen receptor is a potent repressor of proviral reactivation and may serve as a promising therapeutic target in combination with other latency-reversing agents.}, } @article {pmid30292539, year = {2018}, author = {Hug, CB and Vaquerizas, JM}, title = {The Birth of the 3D Genome during Early Embryonic Development.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {12}, pages = {903-914}, doi = {10.1016/j.tig.2018.09.002}, pmid = {30292539}, issn = {0168-9525}, abstract = {The 3D structure of chromatin in the nucleus is important for the regulation of gene expression and the correct deployment of developmental programs. The differentiation of germ cells and early embryonic development (when the zygotic genome is activated and transcription is taking place for the first time) are accompanied by dramatic changes in gene expression and the epigenetic landscape. Recent studies used Hi-C to investigate the 3D chromatin organization during these developmental transitions, uncovering remarkable remodeling of the 3D genome. Here, we highlight the changes described so far and discuss some of the implications that these findings have for our understanding of the mechanisms and functionality of 3D chromatin architecture.}, } @article {pmid30292431, year = {2018}, author = {Brodie, JF and Redford, KH and Doak, DF}, title = {Ecological Function Analysis: Incorporating Species Roles into Conservation.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {840-850}, doi = {10.1016/j.tree.2018.08.013}, pmid = {30292431}, issn = {1872-8383}, abstract = {Effective conservation strategies must ensure that species remain not just extant, but able to maintain key roles in species interactions and in the maintenance of communities and ecosystems. Such ecological functions, however, have not been well incorporated into management or policy. We present a framework for quantifying ecological function that is complementary to population viability analysis (PVA) and that allows function to be integrated into strategic planning processes. Ecological function analysis (EFA) focuses on preventing secondary extinctions and maintaining ecosystem structure, biogeochemical processes, and resiliency. EFA can use a range of modeling approaches and, because most species interactions are relatively weak, EFA needs to be performed for relatively few species or functions, making it a realistic way to improve conservation management.}, } @article {pmid30291951, year = {2018}, author = {Maeno, S and Kajikawa, A and Dicks, L and Endo, A}, title = {Introduction of bifunctional alcohol/acetaldehyde dehydrogenase gene (adhE) in Fructobacillus fructosus settled its fructophilic characteristics.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.09.004}, pmid = {30291951}, issn = {1769-7123}, abstract = {Fructophilic lactic acid bacteria (FLAB) are unique in the sense that they prefer D-fructose over D-glucose as main carbon source. If D-glucose is metabolised, electron acceptors are required and significant levels of acetate are produced. These bacteria are found in environments rich in D-fructose, such as flowers, fruits and the gastrointestinal tract of insects feeding on fructose-rich diets. Fructobacillus spp. are representatives of this unique group, and their fructophilic characteristics are well conserved. In this study, the bifunctional alcohol/acetaldehyde dehydrogenase gene (adhE) from Leuconostoc mesenteroides NRIC 1541T was cloned into a plasmid and transferred to Fructobacillus fructosus NRIC 1058T. Differences in biochemical characteristics between the parental strain (NRIC 1058T) and the transformants were compared. Strain 1-11, transformed with the adhE gene, did not show any fructophilic characteristics, and the strain grew well on D-glucose without external electron acceptors. Accumulation of acetic acid, which was originally seen in the parental strain, was replaced with ethanol in the transformed strain. Furthermore, in silico analyses revealed that strain NRIC 1058T lacked the sugar transporters/permeases and enzymes required for conversion of metabolic intermediates. This may be the reason for poor carbohydrate metabolic properties recorded for FLAB.}, } @article {pmid30291657, year = {2018}, author = {Roulin, A and Uva, V and Romano, A}, title = {A melanin-based trait is more strongly related to body size in the tropics than in temperate regions in the globally distributed barn owl family.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1932-1944}, doi = {10.1111/jeb.13386}, pmid = {30291657}, issn = {1420-9101}, support = {31003A-120517//Swiss National Science Foundation/ ; IZKOZ3_150434//Swiss National Science Foundation/ ; //Wissenschaftskolleg zu Berlin/ ; }, abstract = {Life history traits differ between organisms living in the tropics, Northern and Southern Hemispheres, and sexual selection is thought to be stronger close to the equator than in temperate regions. Although birds are often supposed to be more brightly coloured in the tropics, the current evidence of geographic variation in the intensity of sexual selection and sex-specific natural selection is equivocal. Whether sex-specific traits signal aspects of individual quality better in the tropics than in the temperate regions of the Northern and Southern Hemispheres therefore remains an open question. We examined predictions of this hypothesis in the Tytonidae family (barn owls and their relatives) because females, on average, display larger black spots on the tip of their ventral body feathers than males, and this trait is associated with aspects of individual quality. We measured the size of melanic spots and the wing length of 7893 Tytonidae skins collected worldwide and preserved in natural history museums. The covariation between spot size and wing length was stronger in females than in males, in large- than small-spotted Tyto taxa and close to the equator than in temperate regions. This suggests that selection for spot size, which can be used by owls as an additional cue to assess individual body size and other aspects of phenotypic quality, is stronger in females than in males, particularly near the equator.}, } @article {pmid30291406, year = {2018}, author = {Liu, L and Fang, H and Ding, Y and Zheng, Y and Cai, L and Zheng, S and Zhang, Y}, title = {Transcriptional Regulation Between the Two Global Regulators RovA and CRP in Yersinia pestis biovar Microtus.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1634-1641}, pmid = {30291406}, issn = {1432-0991}, support = {2018CFB184//Natural Science Foundation of Hubei Province/ ; WJ2018H0070//Hubei Province health and family planning scientific research project/ ; 81801984//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Arvicolinae/*microbiology ; Bacterial Proteins/*genetics ; Biofilms ; Cyclic AMP Receptor Protein/*genetics ; Gene Expression Regulation, Bacterial/genetics ; Genes, Regulator/*genetics ; Regulon/genetics ; Transcription Factors/*genetics ; Transcription, Genetic/*genetics ; Virulence/genetics ; Yersinia pestis/*genetics ; }, abstract = {Yersinia pestis is a dangerous bacterial pathogen that can cause plague. Both RovA and cyclic AMP receptor protein (cAMP-CRP) are required for regulating biofilm- and virulence-related genes in Y. pestis. In this study, the transcriptional regulation between RovA and cAMP-CRP were analyzed by using primer extension, quantitative RT-PCR, LacZ fusion, and electrophoretic mobility shift assay. The results indicated that RovA repressed crp transcription in an indirect manner, while that RovA had no regulatory action on cyaA at the transcriptional level. In addition, cAMP-CRP did not regulate the transcription of rovA. Taken together with our previous results, complex regulatory interactions of RovA, cAMP-CRP, and PhoP/PhoQ in Y. pestis were revealed, which would promote us gain deeper understanding about coordinative modulation of biofilm- and virulence-related regulator genes.}, } @article {pmid30291357, year = {2018}, author = {Stein, JC and Yu, Y and Copetti, D and Zwickl, DJ and Zhang, L and Zhang, C and Chougule, K and Gao, D and Iwata, A and Goicoechea, JL and Wei, S and Wang, J and Liao, Y and Wang, M and Jacquemin, J and Becker, C and Kudrna, D and Zhang, J and Londono, CEM and Song, X and Lee, S and Sanchez, P and Zuccolo, A and Ammiraju, JSS and Talag, J and Danowitz, A and Rivera, LF and Gschwend, AR and Noutsos, C and Wu, CC and Kao, SM and Zeng, JW and Wei, FJ and Zhao, Q and Feng, Q and El Baidouri, M and Carpentier, MC and Lasserre, E and Cooke, R and da Rosa Farias, D and da Maia, LC and Dos Santos, RS and Nyberg, KG and McNally, KL and Mauleon, R and Alexandrov, N and Schmutz, J and Flowers, D and Fan, C and Weigel, D and Jena, KK and Wicker, T and Chen, M and Han, B and Henry, R and Hsing, YC and Kurata, N and de Oliveira, AC and Panaud, O and Jackson, SA and Machado, CA and Sanderson, MJ and Long, M and Ware, D and Wing, RA}, title = {Publisher Correction: Genomes of 13 domesticated and wild rice relatives highlight genetic conservation, turnover and innovation across the genus Oryza.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1618}, doi = {10.1038/s41588-018-0261-2}, pmid = {30291357}, issn = {1546-1718}, abstract = {This article was not made open access when initially published online, which was corrected before print publication. In addition, ORCID links were missing for 12 authors and have been added to the HTML and PDF versions of the article.}, } @article {pmid30291356, year = {2018}, author = {Goldmann, JM and Wong, WSW and Pinelli, M and Farrah, T and Bodian, D and Stittrich, AB and Glusman, G and Vissers, LELM and Hoischen, A and Roach, JC and Vockley, JG and Veltman, JA and Solomon, BD and Gilissen, C and Niederhuber, JE}, title = {Author Correction: Parent-of-origin-specific signatures of de novo mutations.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1615}, doi = {10.1038/s41588-018-0226-5}, pmid = {30291356}, issn = {1546-1718}, abstract = {In the version of this article published, the P values for the enrichment of single mutation categories were inadvertently not corrected for multiple testing. After multiple-testing correction, only two of the six mutation categories mentioned are still statistically significant. To reflect this, the text "More specifically, paternally derived DNMs are enriched in transitions in A[.]G contexts, especially ACG>ATG and ATG>ACG (Bonferroni-corrected P = 1.3 × 10-2 and P = 1 × 10-3, respectively). Additionally, we observed overrepresentation of ATA>ACA mutations (Bonferroni-corrected P = 4.28 × 10-2) for DNMs of paternal origin. Among maternally derived DNMs, CCA>CTA, GCA>GTA and TCT>TGT mutations were significantly overrepresented (Bonferroni-corrected P = 4 × 10-4, P = 5 × 10-4, P = 1 × 10-3, respectively)" should read "More specifically, CCA>CTA and GCA>GTA mutations were significantly overenriched on the maternal allele (Bonferroni-corrected P = 0.0192 and P = 0.048, respectively)." Additionally, the last sentence to the legend for Fig. 3b should read "Green boxes highlight the mutation categories that differ significantly" instead of "Green boxes highlight the mutation categories that differ more than 1% of mutation load with a bootstrapping P value <0.05." Corrected versions of Fig. 3b and Supplementary Table 25 appear with the Author Correction.}, } @article {pmid30291310, year = {2018}, author = {Whiten, A}, title = {Foraging skills develop over generations in the wild.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {198-200}, doi = {10.1038/d41586-018-06867-3}, pmid = {30291310}, issn = {1476-4687}, } @article {pmid30291309, year = {2018}, author = {Iruela-Arispe, ML}, title = {A dual origin for blood vessels.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {195-197}, doi = {10.1038/d41586-018-06199-2}, pmid = {30291309}, issn = {1476-4687}, } @article {pmid30291308, year = {2018}, author = {Chanock, SJ}, title = {Gene editing reveals the effect of thousands of variants in a key cancer gene.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {201-202}, doi = {10.1038/d41586-018-06022-y}, pmid = {30291308}, issn = {1476-4687}, } @article {pmid30291305, year = {2018}, author = {Du Toit, A}, title = {Diet and the mammary gland microbiome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {717}, doi = {10.1038/s41579-018-0101-5}, pmid = {30291305}, issn = {1740-1534}, } @article {pmid30291304, year = {2018}, author = {Du Toit, A}, title = {Profilin(g) Asgard archaea.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {717}, doi = {10.1038/s41579-018-0100-6}, pmid = {30291304}, issn = {1740-1534}, } @article {pmid30291191, year = {2018}, author = {Buono, S and Ross, JA and Tasfaout, H and Levy, Y and Kretz, C and Tayefeh, L and Matson, J and Guo, S and Kessler, P and Monia, BP and Bitoun, M and Ochala, J and Laporte, J and Cowling, BS}, title = {Reducing dynamin 2 (DNM2) rescues DNM2-related dominant centronuclear myopathy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11066-11071}, pmid = {30291191}, issn = {1091-6490}, support = {MR/N002768/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Dynamin II/*genetics ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/metabolism ; Mutation/genetics ; Myopathies, Structural, Congenital/*genetics ; Protein Tyrosine Phosphatases, Non-Receptor/genetics ; }, abstract = {Centronuclear myopathies (CNM) are a group of severe muscle diseases for which no effective therapy is currently available. We have previously shown that reduction of the large GTPase DNM2 in a mouse model of the X-linked form, due to loss of myotubularin phosphatase MTM1, prevents the development of the skeletal muscle pathophysiology. As DNM2 is mutated in autosomal dominant forms, here we tested whether DNM2 reduction can rescue DNM2-related CNM in a knock-in mouse harboring the p.R465W mutation (Dnm2RW/+) and displaying a mild CNM phenotype similar to patients with the same mutation. A single intramuscular injection of adeno-associated virus-shRNA targeting Dnm2 resulted in reduction in protein levels 5 wk post injection, with a corresponding improvement in muscle mass and fiber size distribution, as well as an improvement in histopathological CNM features. To establish a systemic treatment, weekly i.p. injections of antisense oligonucleotides targeting Dnm2 were administered to Dnm2RW/+mice for 5 wk. While muscle mass, histopathology, and muscle ultrastructure were perturbed in Dnm2RW/+mice compared with wild-type mice, these features were indistinguishable from wild-type mice after reducing DNM2. Therefore, DNM2 knockdown via two different strategies can efficiently correct the myopathy due to DNM2 mutations, and it provides a common therapeutic strategy for several forms of centronuclear myopathy. Furthermore, we provide an example of treating a dominant disease by targeting both alleles, suggesting that this strategy may be applied to other dominant diseases.}, } @article {pmid30291190, year = {2018}, author = {Shi, S and Markmann, J and Weissmüller, J}, title = {Verifying Larché-Cahn elasticity, a milestone of 20th-century thermodynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10914-10919}, pmid = {30291190}, issn = {1091-6490}, abstract = {Many materials phenomena are governed by the interaction between chemistry and mechanics. However, it was only in the second half of the 20th century that the theory of open system elasticity by Francis Larché and John W. Cahn concatenated the fields of solid mechanics and alloy chemistry. As the theory's central materials descriptors, the open system elastic parameters describe how solids deform under stress when solute can rearrange at equilibrium while the chemical potential is held constant. Here, we report experiments verifying the predictions for these parameters. We study the elasticity of nanoporous Pd-H and Pd-Au-H during load cycles imposed by a dynamic mechanical analyzer. Short diffusion paths afford fast equilibration of H in the local strain gradients that carry the macroscopic elastic deformation. The experiment is in excellent agreement with the theory, confirming a central prediction of one of the key contributions to 20th-century thermodynamics.}, } @article {pmid30291189, year = {2018}, author = {Wang, A and Huen, SC and Luan, HH and Baker, K and Rinder, H and Booth, CJ and Medzhitov, R}, title = {Glucose metabolism mediates disease tolerance in cerebral malaria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11042-11047}, pmid = {30291189}, issn = {1091-6490}, support = {K08 AI128745/AI/NIAID NIH HHS/United States ; K08 DK110424/DK/NIDDK NIH HHS/United States ; T32 AR007107/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Blood-Brain Barrier/immunology/metabolism/parasitology ; Brain/*immunology/*parasitology ; Disease Models, Animal ; Glucose/*immunology/*metabolism ; Immune Tolerance/*immunology ; Inflammation/immunology/metabolism/parasitology ; Malaria, Cerebral/*immunology/*metabolism/parasitology ; Male ; Mice ; Mice, Inbred C57BL ; Parasitemia/immunology ; Plasmodium berghei/immunology ; }, abstract = {Sickness behaviors are a conserved set of stereotypic responses to inflammatory diseases. We recently demonstrated that interfering with inflammation-induced anorexia led to metabolic changes that had profound effects on survival of acute inflammatory conditions. We found that different inflammatory states needed to be coordinated with corresponding metabolic programs to actuate tissue-protective mechanisms. Survival of viral inflammation required intact glucose utilization pathways, whereas survival of bacterial inflammation required alternative fuel substrates and ketogenic programs. We thus hypothesized that organismal metabolism would be important in other classes of infectious inflammation and sought to understand its role in the prototypic parasitic disease malaria. Utilizing the cerebral malaria model, Plasmodium berghei ANKA (PbA) infection in C57BL/6J male mice, we unexpectedly found that inhibition of glycolysis using 2-deoxy glucose (2DG) conferred protection from cerebral malaria. Unlike vehicle-treated animals, 2DG-treated animals did not develop cerebral malaria and survived until ultimately succumbing to fatal anemia. We did not find any differences in parasitemia or pathogen load in affected tissues. There were no differences in the kinetics of anemia. We also did not detect differences in immune infiltration in the brain or in blood-brain barrier permeability. Rather, on pathological analyses performed on the entire brain, we found that 2DG prevented the formation of thrombi and thrombotic complications. Using thromboelastography (TEG), we found that 2DG-treated animals formed clots that were significantly less strong and stable. Together, these data suggest that glucose metabolism is involved in inflammation-induced hemostasis and provide a potential therapeutic target in treatment of cerebral malaria.}, } @article {pmid30291188, year = {2018}, author = {Wang, K and Yang, Z and Qing, D and Ren, F and Liu, S and Zheng, Q and Liu, J and Zhang, W and Dai, C and Wu, M and Chehab, EW and Braam, J and Li, N}, title = {Quantitative and functional posttranslational modification proteomics reveals that TREPH1 plays a role in plant touch-delayed bolting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10265-E10274}, pmid = {30291188}, issn = {1091-6490}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; Gene Expression Regulation, Plant/genetics ; Mechanotransduction, Cellular/genetics ; Phosphoproteins/*genetics ; Phosphorylation/genetics ; Protein Processing, Post-Translational/*genetics ; Proteomics/methods ; Signal Transduction/genetics ; Transcription Factors/genetics ; }, abstract = {Environmental mechanical forces, such as wind and touch, trigger gene-expression regulation and developmental changes, called "thigmomorphogenesis," in plants, demonstrating the ability of plants to perceive such stimuli. In Arabidopsis, a major thigmomorphogenetic response is delayed bolting, i.e., emergence of the flowering stem. The signaling components responsible for mechanotransduction of the touch response are largely unknown. Here, we performed a high-throughput SILIA (stable isotope labeling in Arabidopsis)-based quantitative phosphoproteomics analysis to profile changes in protein phosphorylation resulting from 40 seconds of force stimulation in Arabidopsis thaliana Of the 24 touch-responsive phosphopeptides identified, many were derived from kinases, phosphatases, cytoskeleton proteins, membrane proteins, and ion transporters. In addition, the previously uncharacterized protein TOUCH-REGULATED PHOSPHOPROTEIN1 (TREPH1) became rapidly phosphorylated in touch-stimulated plants, as confirmed by immunoblots. TREPH1 fractionates as a soluble protein and is shown to be required for the touch-induced delay of bolting and gene-expression changes. Furthermore, a nonphosphorylatable site-specific isoform of TREPH1 (S625A) failed to restore touch-induced flowering delay of treph1-1, indicating the necessity of S625 for TREPH1 function and providing evidence consistent with the possible functional relevance of the touch-regulated TREPH1 phosphorylation. Taken together, these findings identify a phosphoprotein player in Arabidopsis thigmomorphogenesis regulation and provide evidence that TREPH1 and its touch-induced phosphorylation may play a role in touch-induced bolting delay, a major component of thigmomorphogenesis.}, } @article {pmid30290846, year = {2018}, author = {Dorà, NJ and Manuel, M and Kleinjan, DJ and Price, DJ and Collinson, JM and Hill, RE and West, JD}, title = {A conditional Pax6 depletion study with no morphological effect on the adult mouse corneal epithelium.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {705}, pmid = {30290846}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; 088876/Z/09/Z//Wellcome Trust/United Kingdom ; }, mesh = {Age Factors ; Animals ; Corneal Diseases/*metabolism/*pathology ; Epithelium, Corneal/*pathology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Transgenic ; PAX6 Transcription Factor/*deficiency ; }, abstract = {OBJECTIVE: The corneas of heterozygous Pax6+/- mice develop abnormally and deteriorate further after birth but it is not known whether the postnatal deterioration is predetermined by abnormal development. Our objective was to identify whether depletion of Pax6 in adult mice caused any corneal abnormalities, similar to those in Pax6+/- mice, where Pax6 levels are low throughout development and adulthood. We used two tamoxifen-inducible, Cre-loxP experimental strategies to deplete Pax6 either ubiquitously or in a restricted range of cell types.

RESULTS: In a preliminary study, ubiquitous depletion of Pax6 by tamoxifen treatment of E9.5 CAG-CreERTg/-;Pax6fl/fl embryos affected eye development. Tamoxifen treatment of 12-week old, adult CAG-CreERTg/-;Pax6fl/+ and CAG-CreERTg/-;Pax6fl/fl mice resulted in weak and/or patchy Pax6 immunostaining in the corneal epithelium but caused no corneal abnormalities. GFP staining in tamoxifen-treated CAG-CreERTg/-;RCE:loxP reporter mice was also patchy. We attribute patchy Pax6 staining to mosaic deletion of the Pax6fl allele, probably caused by mosaic CAG-CreERTg expression. In a parallel study, we treated adult Krt19-CreERTg/-;Pax6fl/+ mice with tamoxifen to try to deplete Pax6 in limbal epithelial stem cells (LESCs) which replenish the corneal epithelium. However, Pax6 staining remained strong after a 12-week chase period so the Krt19-CreERTg/- transgene may have failed to target LESCs.}, } @article {pmid30290844, year = {2018}, author = {Shitie, D and Zewde, T and Molla, Y}, title = {Anemia and other hematological profiles of pregnant women attending antenatal care in Debre Berhan Referral Hospital, North Shoa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {704}, pmid = {30290844}, issn = {1756-0500}, mesh = {Adult ; Anemia/blood/*epidemiology ; Ethiopia/epidemiology ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Hematologic/blood/*epidemiology ; Prenatal Care/*statistics & numerical data ; Thrombocytopenia/blood/*epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: The aim of the study was to determine level of anemia and other hematological profiles in pregnant women attending antenatal care clinic in Debre Berhan Referral Hospital, Ethiopia.

RESULTS: Prevalence of anemia was 2.8% and that of thrombocytopenia was 10.2%. Out of the anemic pregnant mothers, 5 (62.5%) were mildly anemic and 2 (25%) were severely anemic. The factor age < 20 years of mothers was significantly associated with anemia (P < 0.05). In addition, the occurrence of anemia in mothers who visited antenatal clinic two times is two times higher than those mother who visited the antenatal clinic three times. Moreover, the prevalence of anemia is two times more likely to occur in pregnant mothers who did not take iron supplements as compared to their counter parts. According to pregnancy periods; mean white blood cells count was (8.48 ± 3.09, 8.83 ± 2.73, 8.86 ± 2.67) × 109/L for the first, second and third trimesters, respectively. Red blood cells and platelet counts in the first trimester were significantly higher than their corresponding values in third trimester (P < 0.01), whereas mean hemoglobin and hematocrit values were not statistically significant within trimesters (P > 0.05).}, } @article {pmid30290837, year = {2018}, author = {Mungofa, P and Schumann, A and Waldo, L}, title = {Chemical crystal identification with deep learning machine vision.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {703}, pmid = {30290837}, issn = {1756-0500}, support = {2018-70016-27387//National Institute of Food and Agriculture/ ; }, mesh = {Agrochemicals ; *Deep Learning ; *Image Processing, Computer-Assisted ; *Microscopy ; *Pattern Recognition, Automated ; }, abstract = {OBJECTIVE: This study was carried out with the purpose of testing the ability of deep learning machine vision to identify microscopic objects and geometries found in chemical crystal structures.

RESULTS: A database of 6994 images taken with a light microscope showing microscopic crystal details of selected chemical compounds along with 180 images of an unknown chemical was created to train and test, respectively the deep learning models. The models used were GoogLeNet (22 layers deep network) and VGG-16 (16 layers deep network), based on the Caffe framework (University of California, Berkeley, CA) of the DIGITS platform (NVIDIA Corporation, Santa Clara, CA). The two models were successfully trained with the images, having validation accuracy values of 97.38% and 99.65% respectively. Finally, both models were able to correctly identify the unknown chemical sample with a high probability score of 93.34% (GoogLeNet) and 99.41% (VGG-16). The positive results found in this study can be further applied to other unknown sample identification tasks using light microscopy coupled with deep learning machine vision.}, } @article {pmid30290836, year = {2018}, author = {Laureno, R and Lamotte, G and Mark, AS}, title = {Sequential MRI in pontine and extrapontine myelinolysis following rapid correction of hyponatremia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {707}, pmid = {30290836}, issn = {1756-0500}, mesh = {Animals ; Dog Diseases/*diagnostic imaging/etiology/pathology ; Dogs ; Hyponatremia/*complications ; Magnetic Resonance Imaging/*methods ; Myelinolysis, Central Pontine/*diagnostic imaging/etiology/pathology ; }, abstract = {OBJECTIVE: This study describes the MRI changes associated with pontine and extrapontine myelinolysis secondary to rapid correction of hyponatremia in dogs. The authors discuss the relevance of the results for theories of pathogenesis and for diagnosis of patients.

RESULTS: MRI changes associated with pontine and extrapontine myelinolysis first occur on diffusion-weighted imaging. As a generalization, gadolinium enhancement, flair image change and T2 weighted image abnormality appear sequentially.}, } @article {pmid30290831, year = {2018}, author = {Wylie, KM and Blankenship, SA and Tuuli, MG and Macones, GA and Stout, MJ}, title = {Evaluation of patient- versus provider-collected vaginal swabs for microbiome analysis during pregnancy.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {706}, pmid = {30290831}, issn = {1756-0500}, support = {March of Dimes Prematurity Research Center at Washington University in St. Louis//March of Dimes Foundation/ ; T32 HD055172/HD/NICHD NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; K12 HD063086/HD/NICHD NIH HHS/United States ; }, mesh = {Cross-Sectional Studies ; Female ; Health Personnel ; Humans ; *Microbiota ; Pregnancy ; RNA, Ribosomal, 16S ; Self-Examination ; Sequence Analysis, DNA ; Vagina/*microbiology ; Vaginal Smears/methods/*standards ; }, abstract = {OBJECTIVE: We aimed to evaluate if patient- and provider-collected vaginal swabs in pregnant women reflect similar bacterial community characteristics. Pregnant patients performed a self-collected vaginal swab, then underwent a provider-collected swab via speculum exam. DNA pyrosequencing of the 16S rRNA gene V1V3 and V3V5 variable regions was performed. Relative abundance of taxa, alpha diversity, and beta diversity of patient- and provider-collected swabs were compared.

RESULTS: Ninety-four vaginal swabs from 47 women were analyzed. On non-metric multi-dimensional scaling plots, paired patient- and provider-collected swabs clustered closely. The median Pearson correlation coefficient was 0.993 (interquartile range 0.951-0.999) for V1V3 and 0.987 (interquartile range 0.902-0.999) for V3V5. Among paired V1V3 and V3V5 sequences, 83.0% and 73.9% showed strong Pearson correlation (> 0.9), respectively, between patient- and provider-collected swabs; V1V3 and V3V5 sequences with weaker Pearson correlation (< 0.9) had correlation coefficients 0.57-0.89 and 0.49-0.89, respectively. No taxa were preferentially detected by sampling method, with relative abundance of taxa highly conserved. No significant difference in Shannon diversity for V1V3 (p = 0.22) and V3V5 (p = 0.11) sequences among paired samples was seen. We demonstrate that bacterial communities defined from patient- and provider-collected vaginal swabs in pregnant women are similar, validating utilization of patient-collected swabs for vaginal bacterial microbiome sampling during pregnancy.}, } @article {pmid30290792, year = {2018}, author = {Santander, N and Lizama, C and Murgas, L and Contreras, S and Martin, AJM and Molina, P and Quiroz, A and Rivera, K and Salas-Pérez, F and Godoy, A and Rigotti, A and Busso, D}, title = {Transcriptional profiling of embryos lacking the lipoprotein receptor SR-B1 reveals a regulatory circuit governing a neurodevelopmental or metabolic decision during neural tube closure.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {731}, pmid = {30290792}, issn = {1471-2164}, support = {1150399//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; 21170306//CONICYT PhD Fellowship/ ; 1141236//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; 1180347//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; S10 OD010786/OD/NIH HHS/United States ; 1181089//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; 1140342//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; 21130444//CONICYT PhD Fellowship/ ; }, mesh = {Animals ; CD36 Antigens/*deficiency/*genetics ; *Gene Expression Profiling ; *Gene Knockout Techniques ; *Gene Regulatory Networks ; Humans ; Mice ; Neural Tube/*embryology/metabolism ; Neural Tube Defects/genetics/metabolism ; Phenotype ; *Transcription, Genetic ; Weaning ; }, abstract = {BACKGROUND: The high-density lipoprotein receptor SR-B1 mediates cellular uptake of several lipid species, including cholesterol and vitamin E. During early mouse development, SR-B1 is located in the maternal-fetal interface, where it facilitates vitamin E transport towards the embryo. Consequently, mouse embryos lacking SR-B1 are vitamin E-deficient, and around half of them fail to close the neural tube and show cephalic neural tube defects (NTD). Here, we used transcriptomic profiling to identify the molecular determinants of this phenotypic difference between SR-B1 deficient embryos with normal morphology or with NTD.

RESULTS: We used RNA-Seq to compare the transcriptomic profile of three groups of embryos retrieved from SR-B1 heterozygous intercrosses: wild-type E9.5 embryos (WT), embryos lacking SR-B1 that are morphologically normal, without NTD (KO-N) and SR-B1 deficient embryos with this defect (KO-NTD). We identified over 1000 differentially expressed genes: down-regulated genes in KO-NTD embryos were enriched for functions associated to neural development, while up-regulated genes in KO-NTD embryos were enriched for functions related to lipid metabolism. Feeding pregnant dams a vitamin E-enriched diet, which prevents NTD in SR-B1 KO embryos, resulted in mRNA levels for those differentially expressed genes that were more similar to KO-N than to KO-NTD embryos. We used gene regulatory network analysis to identify putative transcriptional regulators driving the different embryonic expression profiles, and identified a regulatory circuit controlled by the androgen receptor that may contribute to this dichotomous expression profile in SR-B1 embryos. Supporting this possibility, the expression level of the androgen receptor correlated strongly with the expression of several genes involved in neural development and lipid metabolism.

CONCLUSIONS: Our analysis shows that normal and defective embryos lacking SR-B1 have divergent expression profiles, explained by a defined set of transcription factors that may explain their divergent phenotype. We propose that distinct expression profiles may be relevant during early development to support embryonic nutrition and neural tube closure.}, } @article {pmid30290791, year = {2018}, author = {Fukui, Y and Aoki, K and Ishii, Y and Tateda, K}, title = {The palatine tonsil bacteriome, but not the mycobiome, is altered in HIV infection.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {127}, pmid = {30290791}, issn = {1471-2180}, abstract = {BACKGROUND: Microbial flora in several organs of HIV-infected individuals have been characterized; however, the palatine tonsil bacteriome and mycobiome and their relationship with each other remain unclear. Determining the palatine tonsil microbiome may provide a better understanding of the pathogenesis of oral and systemic complications in HIV-infected individuals. We conducted a cross-sectional study to characterize the palatine tonsil microbiome in HIV-infected individuals.

RESULTS: Palatine tonsillar swabs were collected from 46 HIV-infected and 20 HIV-uninfected individuals. The bacteriome and mycobiome were analyzed by amplicon sequencing using Illumina MiSeq. The palatine tonsil bacteriome of the HIV-infected individuals differed from that of HIV-uninfected individuals in terms of the decreased relative abundances of the commensal genera Neisseria and Haemophilus. At the species level, the relative abundances and presence of Capnocytophaga ochracea, Neisseria cinerea, and Selenomonas noxia were higher in the HIV-infected group than those in the HIV-uninfected group. In contrast, fungal diversity and composition did not differ significantly between the two groups. Microbial intercorrelation analysis revealed that Candida and Neisseria were negatively correlated with each other in the HIV-infected group. HIV immune status did not influence the palatine tonsil microbiome in the HIV-infected individuals.

CONCLUSIONS: HIV-infected individuals exhibit dysbiotic changes in their palatine tonsil bacteriome, independent of immunological status.}, } @article {pmid30290771, year = {2018}, author = {Rinne, PLH and Paul, LK and van der Schoot, C}, title = {Decoupling photo- and thermoperiod by projected climate change perturbs bud development, dormancy establishment and vernalization in the model tree Populus.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {220}, pmid = {30290771}, issn = {1471-2229}, support = {192013 and 263117//Norwegian Research Council/ ; }, mesh = {Climate Change ; Cold Temperature ; Fraxinus/genetics/physiology ; *Gene Expression Regulation, Plant ; Photoperiod ; Plant Leaves/physiology ; Plant Shoots/growth & development ; Populus/genetics/*physiology ; }, abstract = {BACKGROUND: The performance and survival of deciduous trees depends on their innate ability to anticipate seasonal change. A key event is the timely production of short photoperiod-induced terminal and axillary buds that are dormant and freezing-tolerant. Some observations suggest that low temperature contributes to terminal bud initiation and dormancy. This is puzzling because low temperatures in the chilling range universally release dormancy. It also raises the broader question if the projected climate instabilities, as well as the northward migration of trees, will affect winter preparations and survival of trees.

RESULTS: To gauge the response capacity of trees, we exposed juvenile hybrid aspens to a 10-h short photoperiod in combination with different day/night temperature regimes: high (24/24 °C), moderate (18/18 °C), moderate-low (18/12 °C) and low (12/12 °C), and analysed bud development, dormancy establishment, and marker gene expression. We found that low temperature during the bud formation period (pre-dormancy) upregulated dormancy-release genes of the gibberellin (GA) pathway, including the key GA biosynthesis genes GA20oxidase and GA3oxidase, the GA-receptor gene GID1, as well as GA-inducible enzymes of the 1,3-β-glucanase family that degrade callose at plasmodesmal Dormancy Sphincter Complexes. Simultaneously, this pre-dormancy low temperature perturbed the expression of flowering pathway genes, including CO, FT, CENL1, AGL14, LFY and AP1. In brief, pre-dormancy low temperature compromised bud development, dormancy establishment, and potentially vernalization. On the other hand, a high pre-dormancy temperature prevented dormancy establishment and resulted in flushing.

CONCLUSIONS: The results show that pre-dormancy low temperature represents a form of chilling that antagonizes dormancy establishment. Combined with available field data, this indicates that natural Populus ecotypes have evolved to avoid the adverse effects of high and low temperatures by initiating and completing dormant buds within an approximate temperature-window of 24-12 °C. Global warming and erratic temperature patterns outside this range can therefore endanger the successful propagation of deciduous perennials.}, } @article {pmid30290770, year = {2018}, author = {Wang, J and Ji, C and Li, Q and Zhou, Y and Wu, Y}, title = {Genome-wide analysis of the plant-specific PLATZ proteins in maize and identification of their general role in interaction with RNA polymerase III complex.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {221}, pmid = {30290770}, issn = {1471-2229}, support = {91635303//National Natural Science Foundation of China/ ; XDPB0401//Chinese Academy of Sciences/ ; XDA08020107//Chinese Academy of Sciences/ ; 2016YFD0100500//Ministry of Science and Technology of China/ ; }, mesh = {Arabidopsis/genetics ; Cloning, Molecular ; Gene Expression Regulation, Plant ; Genome, Plant ; Oryza/genetics ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Protein Domains ; Protein Interaction Maps ; RNA Polymerase III/genetics/*metabolism ; RNA, Ribosomal, 5S/metabolism ; RNA, Transfer/metabolism ; Zea mays/*genetics/metabolism ; }, abstract = {BACKGROUND: PLATZ proteins are a novel class of plant-specific zinc-dependent DNA-binding proteins that are classified as transcription factors (TFs). However, their common biochemical features and functions are poorly understood.

RESULT: Here, we identified and cloned 17 PLATZ genes in the maize (Zea mays) genome. All ZmPLATZs were located in nuclei, consistent with their predicted role as TFs. However, none of ZmPLATZs was found to have intrinsic activation properties in yeast. Our recent work shows that FL3 (ZmPLATZ12) interacts with RPC53 and TFC1, two critical factors in the RNA polymerase III (RNAPIII) transcription complex. Using the yeast two-hybrid assay, we determined that seven other PLATZs interacted with both RPC53 and TFC1, whereas three had no protein-protein interaction with these two factors. The other six PLATZs interacted with either RPC53 or TFC1. These findings indicate that ZmPLATZ proteins are generally involved in the modulation of RNAPIII-mediated small non-coding RNA transcription. We also identified all of the PLATZ members in rice (Oryza sativa) and Arabidopsis thaliana and constructed a Maximum likelihood phylogenetic tree for ZmPLATZs. The resulting tree included 44 members and 5 subfamilies.

CONCLUSIONS: This study provides insight into understanding of the phylogenetic relationship, protein structure, expression pattern and cellular localization of PLATZs in maize. We identified nine and thirteen ZmPLATZs that have protein-protein interaction with RPC53 and TFC1 in the current study, respectively. Overall, the characterization and functional analysis of the PLATZ family in maize will pave the way to understanding RNAPIII-mediated regulation in plant development.}, } @article {pmid30290767, year = {2018}, author = {Ren, W and Tao, J and Shi, D and Chen, W and Chen, C}, title = {Involvement of a dihydrodipicolinate synthase gene (FaDHDPS1) in fungal development, pathogenesis and stress responses in Fusarium asiaticum.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {128}, pmid = {30290767}, issn = {1471-2180}, abstract = {BACKGROUND: Dihydrodipicolinate synthase (DHDPS) is an allosteric enzyme, which catalyzes the first unique step of lysine biosynthesis in prokaryotes, higher plants and some fungi. To date, the biological roles of DHDPS in filamentous fungi are poorly understood.

RESULTS: In this study, on the basis of comparative genome resequencing, a DHDPS gene was found to be specific in Fusarium asiaticum, named FaDHDPS1, which showed high amino acid identity to that of entomopathogenic fungus. Subcellular localization of the FaDHDPS1-GFP fusion protein was mainly concentrated in the cytoplasm of conidia and dispersed in the cytoplasm during conidial germination. To reveal the biological functions, both deletion and complementation mutants of FaDHDPS1 were generated. The results showed that the FaDHDPS1 deletion mutant was defective in conidiation, virulence and DON biosynthesis. In addition, deletion of FaDHDPS1 resulted in tolerance to sodium pyruvate, lysine, low temperature and Congo red.

CONCLUSION: Results of this study indicate that FaDHDPS1 plays an important role in the regulation of vegetative differentiation, pathogenesis and adaption to multiple stresses in F. asiaticum.}, } @article {pmid30290758, year = {2018}, author = {Kim, OTP and Nguyen, PT and Shoguchi, E and Hisata, K and Vo, TTB and Inoue, J and Shinzato, C and Le, BTN and Nishitsuji, K and Kanda, M and Nguyen, VH and Nong, HV and Satoh, N}, title = {A draft genome of the striped catfish, Pangasianodon hypophthalmus, for comparative analysis of genes relevant to development and a resource for aquaculture improvement.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {733}, pmid = {30290758}, issn = {1471-2164}, mesh = {Animals ; *Aquaculture ; Catfishes/*genetics/*growth & development ; *Genomics ; Molecular Sequence Annotation ; Sex Determination Processes/genetics ; }, abstract = {BACKGROUND: The striped catfish, Pangasianodon hypophthalmus, is a freshwater and benthopelagic fish common in the Mekong River delta. Catfish constitute a valuable source of dietary protein. Therefore, they are cultured worldwide, and P. hypophthalmus is a food staple in the Mekong area. However, genetic information about the culture stock, is unavailable for breeding improvement, although genetics of the channel catfish, Ictalurus punctatus, has been reported. To acquire genome sequence data as a useful resource for marker-assisted breeding, we decoded a draft genome of P. hypophthalmus and performed comparative analyses.

RESULTS: Using the Illumina platform, we obtained both nuclear and mitochondrial DNA sequences. Molecular phylogeny using the mitochondrial genome confirmed that P. hypophthalmus is a member of the family Pangasiidae and is nested within a clade including the families Cranoglanididae and Ictaluridae. The nuclear genome was estimated at approximately 700 Mb, assembled into 568 scaffolds with an N50 of 14.29 Mbp, and was estimated to contain ~ 28,600 protein-coding genes, comparable to those of channel catfish and zebrafish. Interestingly, zebrafish produce gadusol, but genes for biosynthesis of this sunscreen compound have been lost from catfish genomes. The differences in gene contents between these two catfishes were found in genes for vitamin D-binding protein and cytosolic phospholipase A2, which have lost only in channel catfish. The Hox cluster in catfish genomes comprised seven paralogous groups, similar to that of zebrafish, and comparative analysis clarified catfish lineage-specific losses of A5a, B10a, and A11a. Genes for insulin-like growth factor (IGF) signaling were conserved between the two catfish genomes. In addition to identification of MHC class I and sex determination-related gene loci, the hypothetical chromosomes by comparison with the channel catfish demonstrated the usefulness of the striped catfish genome as a marker resource.

CONCLUSIONS: We developed genomic resources for the striped catfish. Possible conservation of genes for development and marker candidates were confirmed by comparing the assembled genome to that of a model fish, Danio rerio, and to channel catfish. Since the catfish genomic constituent resembles that of zebrafish, it is likely that zebrafish data for gene functions is applicable to striped catfish as well.}, } @article {pmid30290757, year = {2018}, author = {Modepalli, V and Kumar, A and Sharp, JA and Saunders, NR and Nicholas, KR and Lefèvre, C}, title = {Gene expression profiling of postnatal lung development in the marsupial gray short-tailed opossum (Monodelphis domestica) highlights conserved developmental pathways and specific characteristics during lung organogenesis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {732}, pmid = {30290757}, issn = {1471-2164}, support = {OPP10445915//Bill and Melinda Gates Foundation/ ; }, mesh = {Animals ; *Gene Expression Profiling ; Lung/*embryology/physiology ; Monodelphis/*genetics/*growth & development ; Organ Specificity ; Organogenesis/*genetics ; }, abstract = {BACKGROUND: After a short gestation, marsupials give birth to immature neonates with lungs that are not fully developed and in early life the neonate partially relies on gas exchange through the skin. Therefore, significant lung development occurs after birth in marsupials in contrast to eutherian mammals such as humans and mice where lung development occurs predominantly in the embryo. To explore the mechanisms of marsupial lung development in comparison to eutherians, morphological and gene expression analysis were conducted in the gray short-tailed opossum (Monodelphis domestica).

RESULTS: Postnatal lung development of Monodelphis involves three key stages of development: (i) transition from late canalicular to early saccular stages, (ii) saccular and (iii) alveolar stages, similar to developmental stages overlapping the embryonic and perinatal period in eutherians. Differentially expressed genes were identified and correlated with developmental stages. Functional categories included growth factors, extracellular matrix protein (ECMs), transcriptional factors and signalling pathways related to branching morphogenesis, alveologenesis and vascularisation. Comparison with published data on mice highlighted the conserved importance of extracellular matrix remodelling and signalling pathways such as Wnt, Notch, IGF, TGFβ, retinoic acid and angiopoietin. The comparison also revealed changes in the mammalian gene expression program associated with the initiation of alveologenesis and birth, pointing to subtle differences between the non-functional embryonic lung of the eutherian mouse and the partially functional developing lung of the marsupial Monodelphis neonates. The data also highlighted a subset of contractile proteins specifically expressed in Monodelphis during and after alveologenesis.

CONCLUSION: The results provide insights into marsupial lung development and support the potential of the marsupial model of postnatal development towards better understanding of the evolution of the mammalian bronchioalveolar lung.}, } @article {pmid30290031, year = {2018}, author = {Tibble, L and Carvalho, S}, title = {Rethinking the evolution of property and possession: A review and methodological proposition.}, journal = {Evolutionary anthropology}, volume = {27}, number = {6}, pages = {285-296}, doi = {10.1002/evan.21748}, pmid = {30290031}, issn = {1520-6505}, support = {PLP-2016-114//Leverhulme Trust/ ; }, mesh = {Animals ; Anthropology, Physical ; *Behavior, Animal ; *Biological Evolution ; Ethology ; Models, Biological ; Ownership ; Pan troglodytes/*physiology ; }, abstract = {Property is a key feature of modern human society; however, identifying the origin of this multifaceted behavior poses a formidable challenge. Here, we explore the methodologies for researching the origin of property. We discuss how an interdisciplinary approach can shed light on how our human ancestors shifted behaviorally from possessing an object to having exclusive property control over it. Possession occurs when social group members only respect an individual's claim to have exclusive access to an object when the individual has physical control over the object. Property occurs when an individual can claim exclusive access to an object, without challenge, regardless of whether the object is in their physical control or not. Researchers across different disciplines have asked what, if anything, distinguishes human property behavior from the behavior of other animals? Further, when and how did this behavior evolve in our lineage? Due to the considerable methodological challenges posed by researching this topic, few studies have been able to directly address these questions. In this review, we explore the challenges involved in defining property and possession and suggest a two-step approach to interdisciplinary definitions. Next, we evaluate four core approaches to the study of property behavior: evolutionary game theory, ethology, comparative cognition, and developmental psychology. Finally, we propose an empirical study, using an ethological approach to test the presence of property and possessive behavior in a natural setting, using our closest living relative, the chimpanzee (Pan troglodytes). Overall, we argue that this field of research is at a turning point, where the novel integration of various methods may provide an explanation to the origin of property.}, } @article {pmid30289611, year = {2018}, author = {Häggblom, MM and Song, B and Lalucat, J}, title = {Norberto J. Palleroni (1922-2018).}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3459-3461}, doi = {10.1111/1462-2920.14415}, pmid = {30289611}, issn = {1462-2920}, } @article {pmid30289472, year = {2018}, author = {Guillen-Guio, B and Lorenzo-Salazar, JM and González-Montelongo, R and Díaz-de Usera, A and Marcelino-Rodríguez, I and Corrales, A and Cabrera de León, A and Alonso, S and Flores, C}, title = {Genomic Analyses of Human European Diversity at the Southwestern Edge: Isolation, African Influence and Disease Associations in the Canary Islands.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {3010-3026}, pmid = {30289472}, issn = {1537-1719}, abstract = {Despite the genetic resemblance of Canary Islanders to other southern European populations, their geographical isolation and the historical admixture of aborigines (from North Africa) with sub-Saharan Africans and Europeans have shaped a distinctive genetic makeup that likely affects disease susceptibility and health disparities. Based on single nucleotide polymorphism array data and whole genome sequencing (30×), we inferred that the last African admixture took place ∼14 generations ago and estimated that up to 34% of the Canary Islander genome is of recent African descent. The length of regions in homozygosis and the ancestry-related mosaic organization of the Canary Islander genome support the view that isolation has been strongest on the two smallest islands. Furthermore, several genomic regions showed significant and large deviations in African or European ancestry and were significantly enriched in genes involved in prevalent diseases in this community, such as diabetes, asthma, and allergy. The most prominent of these regions were located near LCT and the HLA, two well-known targets of selection, at which 40‒50% of the Canarian genome is of recent African descent according to our estimates. Putative selective signals were also identified in these regions near the SLC6A11-SLC6A1, KCNMB2, and PCDH20-PCDH9 genes. Taken together, our findings provide solid evidence of a significant recent African admixture, population isolation, and adaptation in this part of Europe, with the favoring of African alleles in some chromosome regions. These findings may have medical implications for populations of recent African ancestry.}, } @article {pmid30289455, year = {2018}, author = {Wang, L and Jiang, S and Deng, Z and Dedon, PC and Chen, S}, title = {DNA phosphorothioate modification - a new multi-functional epigenetic system in bacteria.}, journal = {FEMS microbiology reviews}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsre/fuy036}, pmid = {30289455}, issn = {1574-6976}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; }, abstract = {Synthetic phosphorothioate (PT) internucleotide linkages, in which a nonbridging oxygen is replaced by a sulfur atom, share similar physical and chemical properties with phosphodiesters but confer enhanced nuclease tolerance on DNA/RNA, making PTs a valuable biochemical and pharmacological tool. Interestingly, PT modification was recently found to occur naturally in bacteria in a sequence-selective and RP configuration-specific manner. This oxygen-sulfur swap is catalysed by the gene products of dndABCDE, which constitute a defence barrier with DndFGH in some bacterial strains that can distinguish and attack non-PT-modified foreign DNA, resembling DNA methylation-based restriction-modification (R-M) systems. Despite their similar defensive mechanisms, PT- and methylation-based R-M systems have evolved to target different consensus contexts in the host cell because when they share the same recognition sequences, the protective function of each can be impeded. The redox and nucleophilic properties of PT sulfur render PT modification a versatile player in the maintenance of cellular redox homeostasis, epigenetic regulation and environmental fitness. The widespread presence of dnd systems is considered a consequence of extensive horizontal gene transfer, whereas the lability of PT during oxidative stress and the susceptibility of PT to PT-dependent endonucleases provide possible explanations for the ubiquitous but sporadic distribution of PT modification in the bacterial world.}, } @article {pmid30289448, year = {2018}, author = {Swierts, T and Cleary, DFR and de Voogd, NJ}, title = {Prokaryotic communities of Indo-Pacific giant barrel sponges are more strongly influenced by geography than host phylogeny.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, pmid = {30289448}, issn = {1574-6941}, abstract = {Sponges harbor complex communities of microorganisms that carry out essential roles for the functioning and survival of their hosts. In some cases, genetically related sponges from different geographic regions share microbes, while in other cases microbial communities are more similar in unrelated sponges collected from the same location. To better understand how geography and host phylogeny cause variation in the prokaryotic community of sponges, we compared the prokaryotic community of 44 giant barrel sponges (Xestospongia spp.). These sponges belonged to six reproductively isolated genetic groups from eight areas throughout the Indo-Pacific region. Using Illumina sequencing, we obtained 440 000 sequences of the 16S rRNA gene V3V4 variable region that were assigned to 3795 operational taxonomic units (OTUs). The prokaryotic community of giant barrel sponges was characterized by 71 core OTUs (i.e. OTUs present in each specimen) that represented 57.5% of the total number of sequences. The relative abundance of these core OTUs varied significantly among samples, and this variation was predominantly related to the geographic origin of the sample. These results show that in giant barrel sponges, the variation in the prokaryotic community is primarily associated with geography as opposed to phylogenetic relatedness.}, } @article {pmid30289447, year = {2018}, author = {Batista, AMM and Figueredo, CC and Giani, A}, title = {Variability in a permanent cyanobacterial bloom: species-specific responses to environmental drivers.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy197}, pmid = {30289447}, issn = {1574-6941}, abstract = {Cyanobacterial blooms are characterized by intense growth of one or few species that will dominate the phytoplankton community for periods of few months to an entire year or more. However, even during persistent blooms, important seasonal changes among dominant species can be observed. Pampulha reservoir is a tropical eutrophic reservoir presenting permanent blooms. To identify the main species in this environment, a closer analysis performed by microscopy and 16S-rRNA DGGE revealed Cylindrospermopsis raciborskii as highly dominant throughout the year. The second most abundant group comprised species belonging to the Microcystis genus. They followed a well-defined seasonal pattern described by interesting species-specific ecological trends. During thermal stratification in the rainy/warmer season, C. raciborskii dominated in the water column, while Microcystis spp. were abundant at the end of the dry season, a period characterized by higher total phosphorus concentrations. Phylogenetic analyses confirmed the two dominant taxa and their seasonal trends. The results showed that cyanobacteria major controlling factors were strongly species dependent, shifting from physical/climate related (stratification) to more chemical driven (nutrients/eutrophication). Identifying these drivers is therefore essential for the understanding of the bloom dynamics and the real risks associated with each species, and to eventually adopt the most appropriate and effective management strategies.}, } @article {pmid30289197, year = {2019}, author = {Ge, X and Vaccaro, BJ and Thorgersen, MP and Poole, FL and Majumder, EL and Zane, GM and De León, KB and Lancaster, WA and Moon, JW and Paradis, CJ and von Netzer, F and Stahl, DA and Adams, PD and Arkin, AP and Wall, JD and Hazen, TC and Adams, MWW}, title = {Iron- and aluminium-induced depletion of molybdenum in acidic environments impedes the nitrogen cycle.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {152-163}, doi = {10.1111/1462-2920.14435}, pmid = {30289197}, issn = {1462-2920}, support = {DE-AC02-05CH11231//U.S. Department of Energy/ ; }, abstract = {Anthropogenic nitrate contamination is a serious problem in many natural environments. Nitrate removal by microbial action is dependent on the metal molybdenum (Mo), which is required by nitrate reductase for denitrification and dissimilatory nitrate reduction to ammonium. The soluble form of Mo, molybdate (MoO42-), is incorporated into and adsorbed by iron (Fe) and aluminium (Al) (oxy) hydroxide minerals. Herein we used Oak Ridge Reservation (ORR) as a model nitrate-contaminated acidic environment to investigate whether the formation of Fe- and Al-precipitates could impede microbial nitrate removal by depleting Mo. We demonstrate that Fe and Al mineral formation that occurs as the pH of acidic synthetic groundwater is increased, decreases soluble Mo to low picomolar concentrations, a process proposed to mimic environmental diffusion of acidic contaminated groundwater. Analysis of ORR sediments revealed recalcitrant Mo in the contaminated core that co-occurred with Fe and Al, consistent with Mo scavenging by Fe/Al precipitates. Nitrate removal by ORR isolate Pseudomonas fluorescens N2A2 is virtually abolished by Fe/Al precipitate-induced Mo depletion. The depletion of naturally occurring Mo in nitrate- and Fe/Al-contaminated acidic environments like ORR or acid mine drainage sites has the potential to impede microbial-based nitrate reduction thereby extending the duration of nitrate in the environment.}, } @article {pmid30289193, year = {2018}, author = {Nerva, L and Chitarra, W and Siciliano, I and Gaiotti, F and Ciuffo, M and Forgia, M and Varese, GC and Turina, M}, title = {Mycoviruses mediate mycotoxin regulation in Aspergillus ochraceus.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14436}, pmid = {30289193}, issn = {1462-2920}, abstract = {To date, no demonstration of a direct correlation between the presence of mycoviruses and the quantitative or qualitative modulation of mycotoxins has been shown. In our study, we transfected a virus-free ochratoxin A (OTA)-producing isolate of Aspergillus ochraceus with purified mycoviruses from a different A. ochraceus isolate and from Penicillium aurantiogriseum. Among the mycoviruses tested, only Aspergillus ochraceus virus (AoV), a partitivirus widespread in A. ochraceus, caused a specific interaction that led to an overproduction of OTA, which is regulated by the European Commission and is the second most important contaminant of food and feed commodities. Gene expression analysis failed to reveal a specific viral upregulation of the mRNA of genes considered to play a role in the OTA biosynthetic pathway. Furthermore, AoOTApks1, a polyketide synthase gene considered essential for OTA production, is surprisingly absent in the genome of our OTA-producing isolate. The possible biological and evolutionary implications of the mycoviral regulation of mycotoxin production are discussed.}, } @article {pmid30289191, year = {2019}, author = {Liu, Z and Cichocki, N and Hübschmann, T and Süring, C and Ofiţeru, ID and Sloan, WT and Grimm, V and Müller, S}, title = {Neutral mechanisms and niche differentiation in steady-state insular microbial communities revealed by single cell analysis.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {164-181}, doi = {10.1111/1462-2920.14437}, pmid = {30289191}, issn = {1462-2920}, support = {//China Scholarship Council/ ; 100192205//European Regional Development Funds (EFRE-Europe Funds Saxony)/ ; INAR-ABOS, 16KN043222//Federal Ministry of Economic Affairs and Energy Germany (BMWi), Central Innovation Programme for SMEs (ZIM)/ ; //Helmholtz Association/ ; 100192205//European Regional Development Funds/ ; //China Scholarship Council (CSC)/ ; INAR-ABOS,16KN043222//Federal Ministry of Economic Affairs and Energy (BMWi)/ ; }, abstract = {In completely insular microbial communities, evolution of community structure cannot be shaped by the immigration of new members. In addition, when those communities are run in steady state, the influence of environmental factors on their assembly is reduced. Therefore, one would expect similar community structures under steady-state conditions. Yet, in parallel setups, variability does occur. To reveal ecological mechanisms behind this phenomenon, five parallel reactors were studied at the single-cell level for about 100 generations and community structure variations were quantified by ecological measures. Whether community variability can be controlled was tested by implementing soft temperature stressors as potential synchronizers. The low slope of the lognormal rank-order abundance curves indicated a predominance of neutral mechanisms, i.e., where species identity plays no role. Variations in abundance ranks of subcommunities and increase in inter-community pairwise β-diversity over time support this. Niche differentiation was also observed, as indicated by steeper geometric-like rank-order abundance curves and increased numbers of correlations between abiotic and biotic parameters during initial adaptation and after disturbances. Still, neutral forces dominated community assembly. Our findings suggest that complex microbial communities in insular steady-state environments can be difficult to synchronize and maintained in their original or desired structure, as they are non-equilibrium systems.}, } @article {pmid30288919, year = {2019}, author = {Onai, T}, title = {Canonical Wnt/β-catenin and Notch signaling regulate animal/vegetal axial patterning in the cephalochordate amphioxus.}, journal = {Evolution & development}, volume = {21}, number = {1}, pages = {31-43}, doi = {10.1111/ede.12273}, pmid = {30288919}, issn = {1525-142X}, abstract = {In bilaterians, animal/vegetal axial (A/V) patterning is a fundamental early developmental event for establishment of animal/vegetal polarity and following specification of the germ layers (ectoderm, mesoderm, endoderm), of which the evolutionary origin is enigmatic. Understanding A/V axial patterning in a basal animal from each phylum would help to reconstruct the ancestral state of germ layer specification in bilaterians and thus, the evolution of mesoderm, the third intermediate cell layer. Herein, data show that the canonical Wnt/β-catenin (cWnt) and Notch signaling pathways control mesoderm specification from the early endomesoderm in the basal chordate amphioxus. Amphioxus belongs to the deuterostome, one of the main superphyla in Bilateria. In the present study, genes (tcf, dsh, axin, gsk3β) encoding cWnt components were expressed in the endomesoderm during the gastrula stages. Excess cWnt signaling by BIO, a GSK3 inhibitor, expanded the expression domains of outer endomesodermal genes that include future mesodermal ones and suppressed inner endomesodermal and ectodermal genes. Interfering Notch signaling by DAPT, a γ-secretase inhibitor, resulted in decreased expression of ectodermal and endomesodermal markers. These results suggest that cWnt and Notch have important roles in mesoderm specification in amphioxus embryos. The evolution of the mesoderm is also discussed.}, } @article {pmid30287887, year = {2018}, author = {Liu, Y and Zhao, Q and Li, MH and Guan, JY and Zhang, Y and Bai, B and Zhang, W and Liu, WZ and Wu, C and Yuan, X and Li, H and Munro, WJ and Wang, Z and You, L and Zhang, J and Ma, X and Fan, J and Zhang, Q and Pan, JW}, title = {Device-independent quantum random-number generation.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {548-551}, doi = {10.1038/s41586-018-0559-3}, pmid = {30287887}, issn = {1476-4687}, abstract = {Randomness is important for many information processing applications, including numerical modelling and cryptography1,2. Device-independent quantum random-number generation (DIQRNG)3,4 based on the loophole-free violation of a Bell inequality produces genuine, unpredictable randomness without requiring any assumptions about the inner workings of the devices, and is therefore an ultimate goal in the field of quantum information science5-7. Previously reported experimental demonstrations of DIQRNG8,9 were not provably secure against the most general adversaries or did not close the 'locality' loophole of the Bell test. Here we present DIQRNG that is secure against quantum and classical adversaries10-12. We use state-of-the-art quantum optical technology to create, modulate and detect entangled photon pairs, achieving an efficiency of more than 78 per cent from creation to detection at a distance of about 200 metres that greatly exceeds the threshold for closing the 'detection' loophole of the Bell test. By independently and randomly choosing the base settings for measuring the entangled photon pairs and by ensuring space-like separation between the measurement events, we also satisfy the no-signalling condition and close the 'locality' loophole of the Bell test, thus enabling the realization of the loophole-free violation of a Bell inequality. This, along with a high-voltage, high-repetition-rate Pockels cell modulation set-up, allows us to accumulate sufficient data in the experimental time to extract genuine quantum randomness that is secure against the most general adversaries. By applying a large (137.90 gigabits × 62.469 megabits) Toeplitz-matrix hashing technique, we obtain 6.2469 × 107 quantum-certified random bits in 96 hours with a total failure probability (of producing a random number that is not guaranteed to be perfectly secure) of less than 10-5. Our demonstration is a crucial step towards transforming DIQRNG from a concept to a key aspect of practical applications that require high levels of security and thus genuine randomness7. Our work may also help to improve our understanding of the origin of randomness from a fundamental perspective.}, } @article {pmid30287663, year = {2018}, author = {Sheikhi, A}, title = {More than my publications.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {118}, doi = {10.1126/science.362.6410.118}, pmid = {30287663}, issn = {1095-9203}, } @article {pmid30287662, year = {2018}, author = {Park, JW and Lee, JK and Sheu, KM and Wang, L and Balanis, NG and Nguyen, K and Smith, BA and Cheng, C and Tsai, BL and Cheng, D and Huang, J and Kurdistani, SK and Graeber, TG and Witte, ON}, title = {Reprogramming normal human epithelial tissues to a common, lethal neuroendocrine cancer lineage.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {91-95}, doi = {10.1126/science.aat5749}, pmid = {30287662}, issn = {1095-9203}, support = {T32 GM008042/GM/NIGMS NIH HHS/United States ; R01 CA205001/CA/NCI NIH HHS/United States ; P50 CA092131/CA/NCI NIH HHS/United States ; R01 CA178415/CA/NCI NIH HHS/United States ; K99 CA218731/CA/NCI NIH HHS/United States ; P01 CA168585/CA/NCI NIH HHS/United States ; R01 CA172603/CA/NCI NIH HHS/United States ; }, mesh = {Carcinogenesis/*genetics ; Carcinoma, Neuroendocrine/genetics/*pathology ; Cell Line, Tumor ; Cell Lineage ; Cellular Reprogramming/*genetics ; Cellular Reprogramming Techniques ; Drug Delivery Systems ; Epithelial Cells/pathology ; Epithelium/pathology ; Humans ; Lung/*pathology ; Lung Neoplasms/*pathology ; Male ; Prostate/*pathology ; Prostatic Neoplasms/genetics/*pathology ; Retinoblastoma Protein/genetics ; Small Cell Lung Carcinoma/genetics/*pathology ; Tumor Suppressor Protein p53/genetics ; }, abstract = {The use of potent therapies inhibiting critical oncogenic pathways active in epithelial cancers has led to multiple resistance mechanisms, including the development of highly aggressive, small cell neuroendocrine carcinoma (SCNC). SCNC patients have a dismal prognosis due in part to a limited understanding of the molecular mechanisms driving this malignancy and the lack of effective treatments. Here, we demonstrate that a common set of defined oncogenic drivers reproducibly reprograms normal human prostate and lung epithelial cells to small cell prostate cancer (SCPC) and small cell lung cancer (SCLC), respectively. We identify shared active transcription factor binding regions in the reprogrammed prostate and lung SCNCs by integrative analyses of epigenetic and transcriptional landscapes. These results suggest that neuroendocrine cancers arising from distinct epithelial tissues may share common vulnerabilities that could be exploited for the development of drugs targeting SCNCs.}, } @article {pmid30287661, year = {2018}, author = {Kim, HB and Choi, S and Kim, B and Pop-Eleches, C}, title = {The role of education interventions in improving economic rationality.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {83-86}, doi = {10.1126/science.aar6987}, pmid = {30287661}, issn = {1095-9203}, mesh = {Adolescent ; *Choice Behavior ; Female ; Humans ; Random Allocation ; *Social Behavior ; Students ; *Teaching ; *Training Support ; }, abstract = {Schooling rewards people with labor market returns and nonpecuniary benefits in other realms of life. However, there is no experimental evidence showing that education interventions improve individual economic rationality. We examine this hypothesis by studying a randomized 1-year financial support program for education in Malawi that reduced absence and dropout rates and increased scores on a qualification exam of female secondary school students. We measure economic rationality 4 years after the intervention by using lab-in-the-field experiments to create scores of consistency with utility maximization that are derived from revealed preference theory. We find that students assigned to the intervention had higher scores of rationality. The results remain robust after controlling for changes in cognitive and noncognitive skills. Our results suggest that education enhances the quality of economic decision-making.}, } @article {pmid30287660, year = {2018}, author = {Huang, Y and Chen, Y and Castro-Izaguirre, N and Baruffol, M and Brezzi, M and Lang, A and Li, Y and Härdtle, W and von Oheimb, G and Yang, X and Liu, X and Pei, K and Both, S and Yang, B and Eichenberg, D and Assmann, T and Bauhus, J and Behrens, T and Buscot, F and Chen, XY and Chesters, D and Ding, BY and Durka, W and Erfmeier, A and Fang, J and Fischer, M and Guo, LD and Guo, D and Gutknecht, JLM and He, JS and He, CL and Hector, A and Hönig, L and Hu, RY and Klein, AM and Kühn, P and Liang, Y and Li, S and Michalski, S and Scherer-Lorenzen, M and Schmidt, K and Scholten, T and Schuldt, A and Shi, X and Tan, MZ and Tang, Z and Trogisch, S and Wang, Z and Welk, E and Wirth, C and Wubet, T and Xiang, W and Yu, M and Yu, XD and Zhang, J and Zhang, S and Zhang, N and Zhou, HZ and Zhu, CD and Zhu, L and Bruelheide, H and Ma, K and Niklaus, PA and Schmid, B}, title = {Impacts of species richness on productivity in a large-scale subtropical forest experiment.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {80-83}, doi = {10.1126/science.aat6405}, pmid = {30287660}, issn = {1095-9203}, mesh = {*Biodiversity ; Carbon/analysis ; *Climate Change ; *Extinction, Biological ; *Forests ; Phylogeny ; Trees/*classification/physiology ; }, abstract = {Biodiversity experiments have shown that species loss reduces ecosystem functioning in grassland. To test whether this result can be extrapolated to forests, the main contributors to terrestrial primary productivity, requires large-scale experiments. We manipulated tree species richness by planting more than 150,000 trees in plots with 1 to 16 species. Simulating multiple extinction scenarios, we found that richness strongly increased stand-level productivity. After 8 years, 16-species mixtures had accumulated over twice the amount of carbon found in average monocultures and similar amounts as those of two commercial monocultures. Species richness effects were strongly associated with functional and phylogenetic diversity. A shrub addition treatment reduced tree productivity, but this reduction was smaller at high shrub species richness. Our results encourage multispecies afforestation strategies to restore biodiversity and mitigate climate change.}, } @article {pmid30287659, year = {2018}, author = {Dalziel, BD and Kissler, S and Gog, JR and Viboud, C and Bjørnstad, ON and Metcalf, CJE and Grenfell, BT}, title = {Urbanization and humidity shape the intensity of influenza epidemics in U.S. cities.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {75-79}, doi = {10.1126/science.aat6030}, pmid = {30287659}, issn = {1095-9203}, mesh = {Antigens, Viral/genetics/immunology ; Cities/epidemiology ; *Epidemics ; Evolution, Molecular ; Humans ; *Humidity ; Incidence ; Influenza, Human/*epidemiology/*transmission/virology ; Orthomyxoviridae/genetics/immunology ; Population Density ; Spatio-Temporal Analysis ; United States/epidemiology ; *Urbanization ; }, abstract = {Influenza epidemics vary in intensity from year to year, driven by climatic conditions and by viral antigenic evolution. However, important spatial variation remains unexplained. Here we show predictable differences in influenza incidence among cities, driven by population size and structure. Weekly incidence data from 603 cities in the United States reveal that epidemics in smaller cities are focused on shorter periods of the influenza season, whereas in larger cities, incidence is more diffuse. Base transmission potential estimated from city-level incidence data is positively correlated with population size and with spatiotemporal organization in population density, indicating a milder response to climate forcing in metropolises. This suggests that urban centers incubate critical chains of transmission outside of peak climatic conditions, altering the spatiotemporal geometry of herd immunity.}, } @article {pmid30287658, year = {2018}, author = {Couzens, AMC and Prideaux, GJ}, title = {Rapid Pliocene adaptive radiation of modern kangaroos.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {72-75}, doi = {10.1126/science.aas8788}, pmid = {30287658}, issn = {1095-9203}, mesh = {*Adaptation, Biological ; Animals ; Australia ; Biodiversity ; *Climate Change ; Fossils ; Macropodidae/anatomy & histology/*classification/*physiology ; Molar/anatomy & histology ; Phylogeny ; Tooth Crown/anatomy & histology ; }, abstract = {Differentiating between ancient and younger, more rapidly evolved clades is important for determining paleoenvironmental drivers of diversification. Australia possesses many aridity-adapted lineages, the origins of which have been closely linked to late Miocene continental aridification. Using dental macrowear and molar crown height measurements, spanning the past 25 million years, we show that the most iconic Australian terrestrial mammals, "true" kangaroos (Macropodini), adaptively radiated in response to mid-Pliocene grassland expansion rather than Miocene aridity. In contrast, low-crowned, short-faced kangaroos radiated into predominantly browsing niches as the late Cenozoic became more arid, contradicting the view that this was an interval of global browser decline. Our results implicate warm-to-cool climatic oscillations as a trigger for adaptive radiation and refute arguments attributing Pleistocene megafaunal extinction to aridity-forced dietary change.}, } @article {pmid30287657, year = {2018}, author = {Zhou, L and Swearer, DF and Zhang, C and Robatjazi, H and Zhao, H and Henderson, L and Dong, L and Christopher, P and Carter, EA and Nordlander, P and Halas, NJ}, title = {Quantifying hot carrier and thermal contributions in plasmonic photocatalysis.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {69-72}, doi = {10.1126/science.aat6967}, pmid = {30287657}, issn = {1095-9203}, abstract = {Photocatalysis based on optically active, "plasmonic" metal nanoparticles has emerged as a promising approach to facilitate light-driven chemical conversions under far milder conditions than thermal catalysis. However, an understanding of the relation between thermal and electronic excitations has been lacking. We report the substantial light-induced reduction of the thermal activation barrier for ammonia decomposition on a plasmonic photocatalyst. We introduce the concept of a light-dependent activation barrier to account for the effect of light illumination on electronic and thermal excitations in a single unified picture. This framework provides insight into the specific role of hot carriers in plasmon-mediated photochemistry, which is critically important for designing energy-efficient plasmonic photocatalysts.}, } @article {pmid30287656, year = {2018}, author = {He, Y and Hashimoto, M and Song, D and Chen, SD and He, J and Vishik, IM and Moritz, B and Lee, DH and Nagaosa, N and Zaanen, J and Devereaux, TP and Yoshida, Y and Eisaki, H and Lu, DH and Shen, ZX}, title = {Rapid change of superconductivity and electron-phonon coupling through critical doping in Bi-2212.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {62-65}, doi = {10.1126/science.aar3394}, pmid = {30287656}, issn = {1095-9203}, abstract = {Electron-boson coupling plays a key role in superconductivity for many systems. However, in copper-based high-critical temperature (Tc) superconductors, its relation to superconductivity remains controversial despite strong spectroscopic fingerprints. In this study, we used angle-resolved photoemission spectroscopy to find a pronounced correlation between the superconducting gap and the bosonic coupling strength near the Brillouin zone boundary in Bi2Sr2CaCu2O8+δ The bosonic coupling strength rapidly increases from the overdoped Fermi liquid regime to the optimally doped strange metal, concomitant with the quadrupled superconducting gap and the doubled gap-to-Tc ratio across the pseudogap boundary. This synchronized lattice and electronic response suggests that the effects of electronic interaction and the electron-phonon coupling (EPC) reinforce each other in a positive-feedback loop upon entering the strange-metal regime, which in turn drives a stronger superconductivity.}, } @article {pmid30287655, year = {2018}, author = {Cook, KL and Andermann, C and Gimbert, F and Adhikari, BR and Hovius, N}, title = {Glacial lake outburst floods as drivers of fluvial erosion in the Himalaya.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {53-57}, doi = {10.1126/science.aat4981}, pmid = {30287655}, issn = {1095-9203}, abstract = {Himalayan rivers are frequently hit by catastrophic floods that are caused by the failure of glacial lake and landslide dams; however, the dynamics and long-term impacts of such floods remain poorly understood. We present a comprehensive set of observations that capture the July 2016 glacial lake outburst flood (GLOF) in the Bhotekoshi/Sunkoshi River of Nepal. Seismic records of the flood provide new insights into GLOF mechanics and their ability to mobilize large boulders that otherwise prevent channel erosion. Because of this boulder mobilization, GLOF impacts far exceed those of the annual summer monsoon, and GLOFs may dominate fluvial erosion and channel-hillslope coupling many tens of kilometers downstream of glaciated areas. Long-term valley evolution in these regions may therefore be driven by GLOF frequency and magnitude, rather than by precipitation.}, } @article {pmid30287654, year = {2018}, author = {Smith, KT}, title = {Diving within Saturn's rings.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {44-45}, doi = {10.1126/science.aav4175}, pmid = {30287654}, issn = {1095-9203}, } @article {pmid30287653, year = {2018}, author = {Reeves, RG and Voeneky, S and Caetano-Anollés, D and Beck, F and Boëte, C}, title = {Agricultural research, or a new bioweapon system?.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {35-37}, doi = {10.1126/science.aat7664}, pmid = {30287653}, issn = {1095-9203}, mesh = {Agriculture/*standards ; Animals ; *Biological Warfare ; *Gene Editing ; *Gene Transfer, Horizontal ; Insecta/genetics/*virology ; Lycopersicon esculentum ; *Social Control, Formal ; Viruses/*genetics ; Zea mays ; }, } @article {pmid30287652, year = {2018}, author = {Bello, MGD and Knight, R and Gilbert, JA and Blaser, MJ}, title = {Preserving microbial diversity.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {33-34}, doi = {10.1126/science.aau8816}, pmid = {30287652}, issn = {1095-9203}, mesh = {Biological Specimen Banks/*trends ; Gastrointestinal Microbiome/genetics/*physiology ; Global Health ; *Host Microbial Interactions ; Humans ; }, } @article {pmid30287651, year = {2018}, author = {Ong, NP}, title = {Quantum oscillations in an insulator.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {32-33}, doi = {10.1126/science.aau3840}, pmid = {30287651}, issn = {1095-9203}, mesh = {*Quantum Theory ; }, } @article {pmid30287650, year = {2018}, author = {Kareta, MS and Sage, J}, title = {Cancer origins-genetics rules the day.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {30-31}, doi = {10.1126/science.aav1044}, pmid = {30287650}, issn = {1095-9203}, support = {R01 CA206540/CA/NCI NIH HHS/United States ; }, } @article {pmid30287649, year = {2018}, author = {Wallinga, J}, title = {Metropolitan versus small-town influenza.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {29-30}, doi = {10.1126/science.aav1003}, pmid = {30287649}, issn = {1095-9203}, mesh = {Disease Outbreaks ; Environment ; Humans ; *Influenza A virus ; Influenza, Human/*epidemiology ; Social Environment ; }, } @article {pmid30287648, year = {2018}, author = {Cortés, E}, title = {Activating plasmonic chemistry.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {28-29}, doi = {10.1126/science.aav1133}, pmid = {30287648}, issn = {1095-9203}, } @article {pmid30287647, year = {2018}, author = {Sommer, A and Lemmon, MA}, title = {Smoothening out the patches.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {26-27}, doi = {10.1126/science.aav1025}, pmid = {30287647}, issn = {1095-9203}, mesh = {Hedgehog Proteins/*physiology ; *Signal Transduction ; }, } @article {pmid30287646, year = {2018}, author = {Polly, PD}, title = {Marsupial responses to global aridification.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {25-26}, doi = {10.1126/science.aav1602}, pmid = {30287646}, issn = {1095-9203}, mesh = {Animals ; *Marsupialia ; }, } @article {pmid30287645, year = {2018}, author = {Segal, L and Agarwal, D and Isaacson, KJ and Oehmke, TB and Kumar, B and Chen, JS and Cusimano, JM and Negi, S and Tiper, I and Bakermans, AJ and Jensen, MM and Sanganyado, E and Zaidi, SS and Romero-Molina, C and Martínez, SE and Anderson, SM and Santos, GM and De Lella Ezcurra, AL and Farragher, J and Sharma, V and Duncan, G and Dutton-Regester, K and Kim, SA and Yu, S and Schwendimann, BA and Reichardt, JKV and Halder, A and Dennis, AF and Ellwanger, JH and Chiu, YH and Kerman, BE}, title = {NextGen Voices: Quality mentoring.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {22-24}, doi = {10.1126/science.aav5914}, pmid = {30287645}, issn = {1095-9203}, } @article {pmid30287644, year = {2018}, author = {Hand, E}, title = {Sky rivers.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {16-21}, doi = {10.1126/science.362.6410.16}, pmid = {30287644}, issn = {1095-9203}, } @article {pmid30287643, year = {2018}, author = {Grimm, D}, title = {Airlines fight effort to force them to carry lab animals.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {15}, doi = {10.1126/science.362.6410.15}, pmid = {30287643}, issn = {1095-9203}, mesh = {Animal Rights/*legislation & jurisprudence ; Animals ; *Animals, Laboratory ; Aviation/*legislation & jurisprudence ; United States ; United States Government Agencies/legislation & jurisprudence ; }, } @article {pmid30287642, year = {2018}, author = {Wade, L}, title = {New science minister's activism sparks debate.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {14-15}, doi = {10.1126/science.362.6410.14}, pmid = {30287642}, issn = {1095-9203}, mesh = {Biodiversity ; Mexico ; *Plants, Genetically Modified ; *Political Activism ; *Zea mays ; }, } @article {pmid30287641, year = {2018}, author = {Kaiser, J and Couzin-Frankel, J}, title = {Cancer immunotherapy sweeps Nobel for medicine.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {13}, doi = {10.1126/science.362.6410.13}, pmid = {30287641}, issn = {1095-9203}, mesh = {Humans ; Immunotherapy/*methods ; Japan ; Neoplasms/*therapy ; *Nobel Prize ; United States ; }, } @article {pmid30287640, year = {2018}, author = {Cho, A}, title = {Trio earns physics Nobel for turning lasers into tools.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {12}, doi = {10.1126/science.362.6410.12}, pmid = {30287640}, issn = {1095-9203}, } @article {pmid30287639, year = {2018}, author = {Clery, D and Normile, D}, title = {BepiColombo set to probe Mercury's mysteries.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {11-12}, doi = {10.1126/science.362.6410.11}, pmid = {30287639}, issn = {1095-9203}, } @article {pmid30287638, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {8-10}, doi = {10.1126/science.362.6410.8}, pmid = {30287638}, issn = {1095-9203}, } @article {pmid30287637, year = {2018}, author = {Massol-Deyá, A and Stephens, JC and Colón, JL}, title = {Renewable energy for Puerto Rico.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {7}, doi = {10.1126/science.aav5576}, pmid = {30287637}, issn = {1095-9203}, } @article {pmid30287636, year = {2018}, author = {Dougherty, MK and Cao, H and Khurana, KK and Hunt, GJ and Provan, G and Kellock, S and Burton, ME and Burk, TA and Bunce, EJ and Cowley, SWH and Kivelson, MG and Russell, CT and Southwood, DJ}, title = {Saturn's magnetic field revealed by the Cassini Grand Finale.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {}, doi = {10.1126/science.aat5434}, pmid = {30287636}, issn = {1095-9203}, abstract = {During 2017, the Cassini fluxgate magnetometer made in situ measurements of Saturn's magnetic field at distances ~2550 ± 1290 kilometers above the 1-bar surface during 22 highly inclined Grand Finale orbits. These observations refine the extreme axisymmetry of Saturn's internal magnetic field and show displacement of the magnetic equator northward from the planet's physical equator. Persistent small-scale magnetic structures, corresponding to high-degree (>3) axisymmetric magnetic moments, were observed. This suggests secondary shallow dynamo action in the semiconducting region of Saturn's interior. Some high-degree magnetic moments could arise from strong high-latitude concentrations of magnetic flux within the planet's deep dynamo. A strong field-aligned current (FAC) system is located between Saturn and the inner edge of its D-ring, with strength comparable to the high-latitude auroral FACs.}, } @article {pmid30287635, year = {2018}, author = {Hsu, HW and Schmidt, J and Kempf, S and Postberg, F and Moragas-Klostermeyer, G and Seiß, M and Hoffmann, H and Burton, M and Ye, S and Kurth, WS and Horányi, M and Khawaja, N and Spahn, F and Schirdewahn, D and O'Donoghue, J and Moore, L and Cuzzi, J and Jones, GH and Srama, R}, title = {In situ collection of dust grains falling from Saturn's rings into its atmosphere.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {}, doi = {10.1126/science.aat3185}, pmid = {30287635}, issn = {1095-9203}, abstract = {Saturn's main rings are composed of >95% water ice, and the nature of the remaining few percent has remained unclear. The Cassini spacecraft's traversals between Saturn and its innermost D ring allowed its cosmic dust analyzer (CDA) to collect material released from the main rings and to characterize the ring material infall into Saturn. We report the direct in situ detection of material from Saturn's dense rings by the CDA impact mass spectrometer. Most detected grains are a few tens of nanometers in size and dynamically associated with the previously inferred "ring rain." Silicate and water-ice grains were identified, in proportions that vary with latitude. Silicate grains constitute up to 30% of infalling grains, a higher percentage than the bulk silicate content of the rings.}, } @article {pmid30287634, year = {2018}, author = {Waite, JH and Perryman, RS and Perry, ME and Miller, KE and Bell, J and Cravens, TE and Glein, CR and Grimes, J and Hedman, M and Cuzzi, J and Brockwell, T and Teolis, B and Moore, L and Mitchell, DG and Persoon, A and Kurth, WS and Wahlund, JE and Morooka, M and Hadid, LZ and Chocron, S and Walker, J and Nagy, A and Yelle, R and Ledvina, S and Johnson, R and Tseng, W and Tucker, OJ and Ip, WH}, title = {Chemical interactions between Saturn's atmosphere and its rings.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {}, doi = {10.1126/science.aat2382}, pmid = {30287634}, issn = {1095-9203}, abstract = {The Pioneer and Voyager spacecraft made close-up measurements of Saturn's ionosphere and upper atmosphere in the 1970s and 1980s that suggested a chemical interaction between the rings and atmosphere. Exploring this interaction provides information on ring composition and the influence on Saturn's atmosphere from infalling material. The Cassini Ion Neutral Mass Spectrometer sampled in situ the region between the D ring and Saturn during the spacecraft's Grand Finale phase. We used these measurements to characterize the atmospheric structure and material influx from the rings. The atmospheric He/H2 ratio is 10 to 16%. Volatile compounds from the rings (methane; carbon monoxide and/or molecular nitrogen), as well as larger organic-bearing grains, are flowing inward at a rate of 4800 to 45,000 kilograms per second.}, } @article {pmid30287633, year = {2018}, author = {Mitchell, DG and Perry, ME and Hamilton, DC and Westlake, JH and Kollmann, P and Smith, HT and Carbary, JF and Waite, JH and Perryman, R and Hsu, HW and Wahlund, JE and Morooka, MW and Hadid, LZ and Persoon, AM and Kurth, WS}, title = {Dust grains fall from Saturn's D-ring into its equatorial upper atmosphere.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {}, doi = {10.1126/science.aat2236}, pmid = {30287633}, issn = {1095-9203}, abstract = {The sizes of Saturn's ring particles range from meters (boulders) to nanometers (dust). Determination of the rings' ages depends on loss processes, including the transport of dust into Saturn's atmosphere. During the Grand Finale orbits of the Cassini spacecraft, its instruments measured tiny dust grains that compose the innermost D-ring of Saturn. The nanometer-sized dust experiences collisions with exospheric (upper atmosphere) hydrogen and molecular hydrogen, which forces it to fall from the ring into the ionosphere and lower atmosphere. We used the Magnetospheric Imaging Instrument to detect and characterize this dust transport and also found that diffusion dominates above and near the altitude of peak ionospheric density. This mechanism results in a mass deposition into the equatorial atmosphere of ~5 kilograms per second, constraining the age of the D-ring.}, } @article {pmid30287632, year = {2018}, author = {Lamy, L and Zarka, P and Cecconi, B and Prangé, R and Kurth, WS and Hospodarsky, G and Persoon, A and Morooka, M and Wahlund, JE and Hunt, GJ}, title = {The low-frequency source of Saturn's kilometric radiation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {}, doi = {10.1126/science.aat2027}, pmid = {30287632}, issn = {1095-9203}, abstract = {Understanding how auroral radio emissions are produced by magnetized bodies requires in situ measurements within their source region. Saturn's kilometric radiation (SKR) has been widely used as a remote proxy of Saturn's magnetosphere. We present wave and plasma measurements from the Cassini spacecraft during its ring-grazing high-inclination orbits, which passed three times through the high-altitude SKR emission region. Northern dawn-side, narrow-banded radio sources were encountered at frequencies of 10 to 20 kilohertz, within regions of upward currents mapping to the ultraviolet auroral oval. The kilometric waves were produced on the extraordinary mode by the cyclotron maser instability from 6- to 12-kilo-electron volt electron beams and radiated quasi-perpendicularly to the auroral magnetic field lines. The SKR low-frequency sources appear to be strongly controlled by time-variable magnetospheric electron densities.}, } @article {pmid30287631, year = {2018}, author = {Roussos, E and Kollmann, P and Krupp, N and Kotova, A and Regoli, L and Paranicas, C and Mitchell, DG and Krimigis, SM and Hamilton, D and Brandt, P and Carbary, J and Christon, S and Dialynas, K and Dandouras, I and Hill, ME and Ip, WH and Jones, GH and Livi, S and Mauk, BH and Palmaerts, B and Roelof, EC and Rymer, A and Sergis, N and Smith, HT}, title = {A radiation belt of energetic protons located between Saturn and its rings.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {}, doi = {10.1126/science.aat1962}, pmid = {30287631}, issn = {1095-9203}, abstract = {Saturn has a sufficiently strong dipole magnetic field to trap high-energy charged particles and form radiation belts, which have been observed outside its rings. Whether stable radiation belts exist near the planet and inward of the rings was previously unknown. The Cassini spacecraft's Magnetosphere Imaging Instrument obtained measurements of a radiation belt that lies just above Saturn's dense atmosphere and is decoupled from the rest of the magnetosphere by the planet's A- to C-rings. The belt extends across the D-ring and comprises protons produced through cosmic ray albedo neutron decay and multiple charge-exchange reactions. These protons are lost to atmospheric neutrals and D-ring dust. Strong proton depletions that map onto features on the D-ring indicate a highly structured and diverse dust environment near Saturn.}, } @article {pmid30287619, year = {2018}, author = {Freeman, R and Han, M and Álvarez, Z and Lewis, JA and Wester, JR and Stephanopoulos, N and McClendon, MT and Lynsky, C and Godbe, JM and Sangji, H and Luijten, E and Stupp, SI}, title = {Reversible self-assembly of superstructured networks.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {808-813}, doi = {10.1126/science.aat6141}, pmid = {30287619}, issn = {1095-9203}, support = {R01 EB018358/EB/NIBIB NIH HHS/United States ; }, abstract = {Soft structures in nature, such as protein assemblies, can organize reversibly into functional and often hierarchical architectures through noncovalent interactions. Molecularly encoding this dynamic capability in synthetic materials has remained an elusive goal. We report on hydrogels of peptide-DNA conjugates and peptides that organize into superstructures of intertwined filaments that disassemble upon the addition of molecules or changes in charge density. Experiments and simulations demonstrate that this response requires large-scale spatial redistribution of molecules directed by strong noncovalent interactions among them. Simulations also suggest that the chemically reversible structures can only occur within a limited range of supramolecular cohesive energies. Storage moduli of the hydrogels change reversibly as superstructures form and disappear, as does the phenotype of neural cells in contact with these materials.}, } @article {pmid30287618, year = {2018}, author = {Chen, X and Sun, X and Yang, W and Yang, B and Zhao, X and Chen, S and He, L and Chen, H and Yang, C and Xiao, L and Chang, Z and Guo, J and He, J and Zhang, F and Zheng, F and Hu, Z and Yang, Z and Lou, J and Zheng, W and Qi, H and Xu, C and Zhang, H and Shan, H and Zhou, XJ and Wang, Q and Shi, Y and Lai, L and Li, Z and Liu, W}, title = {An autoimmune disease variant of IgG1 modulates B cell activation and differentiation.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {700-705}, doi = {10.1126/science.aap9310}, pmid = {30287618}, issn = {1095-9203}, abstract = {The maintenance of autoreactive B cells in a quiescent state is crucial for preventing autoimmunity. Here we identify a variant of human immunoglobulin G1 (IgG1) with a Gly396→Arg substitution (hIgG1-G396R), which positively correlates with systemic lupus erythematosus. In induced lupus models, murine homolog Gly390→Arg (G390R) knockin mice generate excessive numbers of plasma cells, leading to a burst of broad-spectrum autoantibodies. This enhanced production of antibodies is also observed in hapten-immunized G390R mice, as well as in influenza-vaccinated human G396R homozygous carriers. This variant potentiates the phosphorylation of the IgG1 immunoglobulin tail tyrosine (ITT) motif. This, in turn, alters the availability of phospho-ITT to trigger longer adaptor protein Grb2 dwell times in immunological synapses, leading to hyper-Grb2-Bruton's tyrosine kinase (Btk) signaling upon antigen binding. Thus, the hIgG1-G396R variant is important for both lupus pathogenesis and antibody responses after vaccination.}, } @article {pmid30287617, year = {2018}, author = {Kujirai, T and Ehara, H and Fujino, Y and Shirouzu, M and Sekine, SI and Kurumizaka, H}, title = {Structural basis of the nucleosome transition during RNA polymerase II passage.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6414}, pages = {595-598}, doi = {10.1126/science.aau9904}, pmid = {30287617}, issn = {1095-9203}, mesh = {Chromatin/genetics ; Cryoelectron Microscopy ; DNA/chemistry/metabolism ; *Epigenesis, Genetic ; Histones/chemistry/metabolism ; Humans ; Nucleosomes/*chemistry/*metabolism/ultrastructure ; RNA Polymerase II/*chemistry/*metabolism/ultrastructure ; *Transcription, Genetic ; }, abstract = {Genomic DNA forms chromatin, in which the nucleosome is the repeating unit. The mechanism by which RNA polymerase II (RNAPII) transcribes the nucleosomal DNA remains unclear. Here we report the cryo-electron microscopy structures of RNAPII-nucleosome complexes in which RNAPII pauses at the superhelical locations SHL(-6), SHL(-5), SHL(-2), and SHL(-1) of the nucleosome. RNAPII pauses at the major histone-DNA contact sites, and the nucleosome interactions with the RNAPII subunits stabilize the pause. These structures reveal snapshots of nucleosomal transcription, in which RNAPII gradually tears DNA from the histone surface while preserving the histone octamer. The nucleosomes in the SHL(-1) complexes are bound to a "foreign" DNA segment, which might explain the histone transfer mechanism. These results provide the foundations for understanding chromatin transcription and epigenetic regulation.}, } @article {pmid30287488, year = {2018}, author = {Omari, S and Makareeva, E and Roberts-Pilgrim, A and Mirigian, L and Jarnik, M and Ott, C and Lippincott-Schwartz, J and Leikin, S}, title = {Noncanonical autophagy at ER exit sites regulates procollagen turnover.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10099-E10108}, pmid = {30287488}, issn = {1091-6490}, mesh = {3T3 Cells ; Animals ; Autophagy/*physiology ; Cell Line ; Collagen Type I/metabolism ; Endoplasmic Reticulum/*metabolism ; Golgi Apparatus/metabolism ; Lysosomes/metabolism ; Mice ; Osteoblasts/metabolism ; Procollagen/*metabolism ; Protein Transport/physiology ; }, abstract = {Type I collagen is the main component of bone matrix and other connective tissues. Rerouting of its procollagen precursor to a degradative pathway is crucial for osteoblast survival in pathologies involving excessive intracellular buildup of procollagen that is improperly folded and/or trafficked. What cellular mechanisms underlie this rerouting remains unclear. To study these mechanisms, we employed live-cell imaging and correlative light and electron microscopy (CLEM) to examine procollagen trafficking both in wild-type mouse osteoblasts and osteoblasts expressing a bone pathology-causing mutant procollagen. We found that although most procollagen molecules successfully trafficked through the secretory pathway in these cells, a subpopulation did not. The latter molecules appeared in numerous dispersed puncta colocalizing with COPII subunits, autophagy markers and ubiquitin machinery, with more puncta seen in mutant procollagen-expressing cells. Blocking endoplasmic reticulum exit site (ERES) formation suppressed the number of these puncta, suggesting they formed after procollagen entry into ERESs. The punctate structures containing procollagen, COPII, and autophagic markers did not move toward the Golgi but instead were relatively immobile. They appeared to be quickly engulfed by nearby lysosomes through a bafilomycin-insensitive pathway. CLEM and fluorescence recovery after photobleaching experiments suggested engulfment occurred through a noncanonical form of autophagy resembling microautophagy of ERESs. Overall, our findings reveal that a subset of procollagen molecules is directed toward lysosomal degradation through an autophagic pathway originating at ERESs, providing a mechanism to remove excess procollagen from cells.}, } @article {pmid30287487, year = {2018}, author = {Gal, A and Sorrentino, A and Kahil, K and Pereiro, E and Faivre, D and Scheffel, A}, title = {Native-state imaging of calcifying and noncalcifying microalgae reveals similarities in their calcium storage organelles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {11000-11005}, pmid = {30287487}, issn = {1091-6490}, mesh = {Acids/metabolism ; Calcification, Physiologic/*physiology ; Calcium/*metabolism ; Calcium Carbonate/metabolism ; Chlamydomonas reinhardtii/metabolism ; Haptophyta/metabolism ; Homeostasis/physiology ; Microalgae/*metabolism ; Minerals/metabolism ; Oceans and Seas ; Organelles/*metabolism ; Phosphorus/metabolism ; Polyphosphates/metabolism ; }, abstract = {Calcium storage organelles are common to all eukaryotic organisms and play a pivotal role in calcium signaling and cellular calcium homeostasis. In most organelles, the intraorganellar calcium concentrations rarely exceed micromolar levels. Acidic organelles called acidocalcisomes, which concentrate calcium into dense phases together with polyphosphates, are an exception. These organelles have been identified in diverse organisms, but, to date, only in cells that do not form calcium biominerals. Recently, a compartment storing molar levels of calcium together with phosphorous was discovered in an intracellularly calcifying alga, the coccolithophore Emiliania huxleyi, raising a possible connection between calcium storage organelles and calcite biomineralization. Here we used cryoimaging and cryospectroscopy techniques to investigate the anatomy and chemical composition of calcium storage organelles in their native state and at nanometer-scale resolution. We show that the dense calcium phase inside the calcium storage compartment of the calcifying coccolithophore Pleurochrysis carterae and the calcium phase stored in acidocalcisomes of the noncalcifying alga Chlamydomonas reinhardtii have common features. Our observations suggest that this strategy for concentrating calcium is a widespread trait and has been adapted for coccolith formation. The link we describe between acidocalcisomal calcium storage and calcium storage in coccolithophores implies that our physiological and molecular genetic understanding of acidocalcisomes could have relevance to the calcium pathway underlying coccolithophore calcification, offering a fresh entry point for mechanistic investigations on the adaptability of this process to changing oceanic conditions.}, } @article {pmid30287486, year = {2018}, author = {Seigneur, E and Polepalli, JS and Südhof, TC}, title = {Cbln2 and Cbln4 are expressed in distinct medial habenula-interpeduncular projections and contribute to different behavioral outputs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10235-E10244}, pmid = {30287486}, issn = {1091-6490}, support = {R37 MH052804/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; Habenula/*metabolism ; Male ; Maze Learning/physiology ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/*metabolism ; Neurons/metabolism ; Protein Precursors/*metabolism ; Spatial Learning/physiology ; Synapses/metabolism ; Synaptic Transmission/physiology ; }, abstract = {Cerebellins are important neurexin ligands that remain incompletely understood. Two critical questions in particular remain unanswered: do different cerebellins perform distinct functions, and do these functions act in the initial establishment of synapses or in rendering nascent synapses capable of normal synaptic transmission? Here we show that in mice, Cbln2 and Cbln4 are expressed in the medial habenula (MHb) nucleus in different types of neurons that project to distinct target neurons in the interpeduncular nucleus. Conditional genetic deletion of Cbln2 in the MHb impaired synaptic transmission at Cbln2+ synapses in the interpeduncular neurons within 3 wk, but decreased synapse numbers only after 3 mo, suggesting a functional, but not a structural, requirement for Cbln2 in synapses formed by Cbln2-expressing neurons. In contrast, genetic deletions of Cbln4 in the MHb had no major effect on synaptic transmission or synapse numbers in interpeduncular target neurons. Nevertheless, MHb ablation of both Cbln2 and Cbln4 significantly impaired behavioral responses in mice, but affected different types of behaviors. Specifically, Cbln2 MHb deletions decreased spatial learning, as measured in the water T-maze, whereas Cbln4 MHb deletions increased anxiety levels, as monitored in the open field test and elevated plus maze. Thus, Cbln2 and Cbln4 are expressed in distinct MHb neurons that contribute to different behaviors.}, } @article {pmid30287485, year = {2018}, author = {Dow, M and Pyke, RM and Tsui, BY and Alexandrov, LB and Nakagawa, H and Taniguchi, K and Seki, E and Harismendy, O and Shalapour, S and Karin, M and Carter, H and Font-Burgada, J}, title = {Integrative genomic analysis of mouse and human hepatocellular carcinoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9879-E9888}, pmid = {30287485}, issn = {1091-6490}, support = {R37 AI043477/AI/NIAID NIH HHS/United States ; P42 ES010337/ES/NIEHS NIH HHS/United States ; R01 DK085252/DK/NIDDK NIH HHS/United States ; T15 LM011271/LM/NLM NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 CA118165/CA/NCI NIH HHS/United States ; U01 AA022614/AA/NIAAA NIH HHS/United States ; R01 AI043477/AI/NIAID NIH HHS/United States ; DP5 OD017937/OD/NIH HHS/United States ; R00 CA191152/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomarkers, Tumor/*genetics ; Carcinoma, Hepatocellular/*genetics/pathology ; Disease Models, Animal ; *Gene Expression Profiling ; Genomics/*methods ; Humans ; Liver Neoplasms/*genetics/pathology ; Liver Neoplasms, Experimental/*genetics/pathology ; Mice ; Mice, Inbred C57BL ; Transcriptome ; }, abstract = {Cancer genomics has enabled the exhaustive molecular characterization of tumors and exposed hepatocellular carcinoma (HCC) as among the most complex cancers. This complexity is paralleled by dozens of mouse models that generate histologically similar tumors but have not been systematically validated at the molecular level. Accurate models of the molecular pathogenesis of HCC are essential for biomedical progress; therefore we compared genomic and transcriptomic profiles of four separate mouse models [MUP transgenic, TAK1-knockout, carcinogen-driven diethylnitrosamine (DEN), and Stelic Animal Model (STAM)] with those of 987 HCC patients with distinct etiologies. These four models differed substantially in their mutational load, mutational signatures, affected genes and pathways, and transcriptomes. STAM tumors were most molecularly similar to human HCC, with frequent mutations in Ctnnb1, similar pathway alterations, and high transcriptomic similarity to high-grade, proliferative human tumors with poor prognosis. In contrast, TAK1 tumors better reflected the mutational signature of human HCC and were transcriptionally similar to low-grade human tumors. DEN tumors were least similar to human disease and almost universally carried the Braf V637E mutation, which is rarely found in human HCC. Immune analysis revealed that strain-specific MHC-I genotype can influence the molecular makeup of murine tumors. Thus, different mouse models of HCC recapitulate distinct aspects of HCC biology, and their use should be adapted to specific questions based on the molecular features provided here.}, } @article {pmid30287212, year = {2018}, author = {daSilva, LLP and Mardones, GA}, title = {HIV/SIV-Nef: Pas de trois Choreographies to Evade Immunity.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {889-891}, doi = {10.1016/j.tim.2018.09.003}, pmid = {30287212}, issn = {1878-4380}, abstract = {Nef is a major pathogenic factor of human and simian immunodeficiency viruses that hijacks protein trafficking through physical interaction with vesicle coats. This alters the subcellular localization of proteins involved in immunity and neutralizes their function. Understanding the structural bases for these interactions could reveal new targets for antiviral intervention.}, } @article {pmid30287118, year = {2018}, author = {Harder, M and Reeves, W and Byers, C and Santiago, M and Veeman, M}, title = {Multiple inputs into a posterior-specific regulatory network in the Ciona notochord.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.09.021}, pmid = {30287118}, issn = {1095-564X}, abstract = {The gene regulatory networks underlying Ciona notochord fate specification and differentiation have been extensively investigated, but the regulatory basis for regionalized expression within the notochord is not understood. Here we identify three notochord-expressed genes, C11.331, C12.115 and C8.891, with strongly enriched expression in the secondary notochord cells at the posterior tip of the tail. C11.331 and C12.115 share a distinctive expression pattern that is highly enriched in the secondary notochord lineage but also graded within that lineage with the strongest expression at the posterior tip. Both genes show similar responses to pharmacological perturbations of Wnt and FGF signaling, consistent with an important role for Wnt and FGF ligands expressed at the tail tip. Reporter analysis indicates that the C11.331 cis-regulatory regions are extensively distributed, with multiple non-overlapping regions conferring posterior notochord-enriched expression. Fine-scale analysis of a minimal cis-regulatory module identifies discrete positive and negative elements including a strong silencer. Truncation of the silencer region leads to increased expression in the primary notochord, indicating that C11.331 expression is influenced by putative regulators of primary versus secondary notochord fate. The minimal CRM contains predicted ETS, GATA, LMX and Myb sites, all of which lead to reduced expression in secondary notochord when mutated. These results show that the posterior-enriched notochord expression of C11.331 depends on multiple inputs, including Wnt and FGF signals from the tip of the tail, multiple notochord-specific regulators, and yet-to-be identified regulators of regional identity within the notochord.}, } @article {pmid30287096, year = {2018}, author = {Wienert, B and Martyn, GE and Funnell, APW and Quinlan, KGR and Crossley, M}, title = {Wake-up Sleepy Gene: Reactivating Fetal Globin for β-Hemoglobinopathies.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {12}, pages = {927-940}, doi = {10.1016/j.tig.2018.09.004}, pmid = {30287096}, issn = {0168-9525}, abstract = {Disorders in hemoglobin (hemoglobinopathies) were the first monogenic diseases to be characterized and remain among the most common and best understood genetic conditions. Moreover, the study of the β-globin locus provides a textbook example of developmental gene regulation. The fetal γ-globin genes (HBG1/HBG2) are ordinarily silenced around birth, whereupon their expression is replaced by the adult β-globin genes (HBB primarily and HBD). Over 50 years ago it was recognized that mutations that cause lifelong persistence of fetal γ-globin expression ameliorate the debilitating effects of mutations in β-globin. Since then, research has focused on therapeutically reactivating the fetal γ-globin genes. Here, we summarize recent discoveries, focusing on the influence of genome editing technologies, including CRISPR-Cas9, and emerging gene therapy approaches.}, } @article {pmid30287080, year = {2018}, author = {Feinberg, DR and Jones, BC and Armstrong, MM}, title = {Sensory Exploitation, Sexual Dimorphism, and Human Voice Pitch.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {901-903}, doi = {10.1016/j.tree.2018.09.007}, pmid = {30287080}, issn = {1872-8383}, abstract = {Selection for low male voice pitch is generally assumed to occur because it is a valid cue of formidability. Here we summarize recent empirical challenges to this hypothesis. We also outline an alternative account in which selection for low male voice pitch is a byproduct of sensory exploitation.}, } @article {pmid30286807, year = {2018}, author = {Pérez-Losada, M and Authelet, KJ and Hoptay, CE and Kwak, C and Crandall, KA and Freishtat, RJ}, title = {Pediatric asthma comprises different phenotypic clusters with unique nasal microbiotas.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {179}, pmid = {30286807}, issn = {2049-2618}, support = {K12 HL119994/HL/NHLBI NIH HHS/United States ; K12 HD001399/HD/NICHD NIH HHS/United States ; UL1 TR000075/TR/NCATS NIH HHS/United States ; R01 MD007075/MD/NIMHD NIH HHS/United States ; }, abstract = {BACKGROUND: Pediatric asthma is the most common chronic childhood disease in the USA, currently affecting ~ 7 million children. This heterogeneous syndrome is thought to encompass various disease phenotypes of clinically observable characteristics, which can be statistically identified by applying clustering approaches to patient clinical information. Extensive evidence has shown that the airway microbiome impacts both clinical heterogeneity and pathogenesis in pediatric asthma. Yet, so far, airway microbiotas have been consistently neglected in the study of asthma phenotypes. Here, we couple extensive clinical information with 16S rRNA high-throughput sequencing to characterize the microbiota of the nasal cavity in 163 children and adolescents clustered into different asthma phenotypes.

RESULTS: Our clustering analyses identified three statistically distinct phenotypes of pediatric asthma. Four core OTUs of the pathogenic genera Moraxella, Staphylococcus, Streptococcus, and Haemophilus were present in at least 95% of the studied nasal microbiotas. Phyla (Proteobacteria, Actinobacteria, and Bacteroidetes) and genera (Moraxella, Corynebacterium, Dolosigranulum, and Prevotella) abundances, community composition, and structure varied significantly (0.05 < P ≤ 0.0001) across asthma phenotypes and one of the clinical variables (preterm birth). Similarly, microbial networks of co-occurrence of bacterial genera revealed different bacterial associations across asthma phenotypes.

CONCLUSIONS: This study shows that children and adolescents with different clinical characteristics of asthma also show different nasal bacterial profiles, which is indicative of different phenotypes of the disease. Our work also shows how clinical and microbial information could be integrated to validate and refine asthma classification systems and develop biomarkers of disease.}, } @article {pmid30286801, year = {2018}, author = {Asgedom, SW and Tesfaye, D and Nirayo, YL and Atey, TM}, title = {Time to death and risk factors among tuberculosis patients in Northern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {696}, pmid = {30286801}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Humans ; Infant ; Male ; Middle Aged ; Risk Factors ; Time Factors ; Tuberculosis/*diagnosis/*drug therapy/*mortality ; Young Adult ; }, abstract = {OBJECTIVE: The main objective of this study was to assess time to death and associated risk factors among tuberculosis (TB) patients.

RESULTS: A total of 769 TB patients were studied and of those, 87 (11.3%) patients died. All of the deaths occurred within 7 months of anti-tuberculosis therapy. Extra-pulmonary TB (AHR = 17.376, 95% CI; 3.88-77.86, p < 0.001) as compared to pulmonary TB and cotrimoxazole prophylaxis therapy (CPT) (AHR = 0.15, 95% CI; 0.03-0.74, p = 0.02) were found to be the predictors of mortality. We noticed higher rates of mortality. Extra-pulmonary TB patients have high risk and TB-HIV co-infected patients who received CPT have low risk of death. Improving early diagnosis of extra-pulmonary TB and early CPT initiation of TB-HIV co-infected patients could minimize patient's mortality.}, } @article {pmid30286796, year = {2018}, author = {Hasan, MI and Hassan, MZ and Bulbul, MMI and Joarder, T and Chisti, MJ}, title = {Iceberg of workplace violence in health sector of Bangladesh.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {702}, pmid = {30286796}, issn = {1756-0500}, mesh = {Adult ; Bangladesh/epidemiology ; Female ; Health Personnel/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Primary Health Care/*statistics & numerical data ; Tertiary Healthcare/*statistics & numerical data ; Workplace Violence/*statistics & numerical data ; }, abstract = {OBJECTIVES: 'Negligence of Physicians' and 'Wrong Treatment' have become commonly-used phrases in print and electronic media of Bangladesh, while violence against healthcare workers has always been under-reported. Unfortunately, there is little evidence regarding physical violence against healthcare workers, while there is no data on the magnitude of psychological violence. The objective of this study was to quantify and explore the magnitude of workplace violence in health sector of Bangladesh to guide future research and adopt preventive policies.

RESULTS: The Majority (96%, n = 54) of the violence cases were physical in nature and 91% violence (n = 51) took place in public healthcare settings. More than one-third (39%) of the violence cases occurred at primary healthcare level and one-third (39%) at tertiary healthcare level. It was mostly (61%) the entry-level physicians who were affected by violence. The report reveals the tip of the iceberg of workplace violence in health sector of Bangladesh. Further studies should be undertaken to assess the prevalence, magnitude, and associated factors for workplace violence against healthcare workers.}, } @article {pmid30286794, year = {2018}, author = {Serwer, P and Hunter, B and Wright, ET}, title = {Cell-gel interactions of in-gel propagating bacteria.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {699}, pmid = {30286794}, issn = {1756-0500}, mesh = {*Agar ; Bacillaceae/*physiology ; *Bacterial Physiological Phenomena ; Escherichia coli/*physiology ; *Gels ; *Microscopy, Electron ; }, abstract = {OBJECTIVE: Our immediate objective is to test the data-suggested possibility that in-agarose gel bacterial propagation causes gel fiber dislocation and alteration of cell distribution. We also test the further effect of lowering water activity. We perform these tests with both Gram-negative and Gram-positive bacteria. Data are obtained via electron microscopy of thin sections, which provides the first images of both bacteria and gel fibers in gel-supported bacterial lawns. The long-term objective is analysis of the effects of in-gel propagation on the DNA packaging of phages.

RESULTS: We find that agarose gel-supported cells in lawns of Escherichia coli and Lysinibacillus (1) are primarily in clusters that increase in size with time and are surrounded by gel fibers, and (2) sometimes undergo gel-induced, post-duplication rotation and translation. Bacterial growth-induced dislocation of gel fibers is observed. One reason for clustering is that clustering promotes growth by increasing the growth-derived force applied to the gel fibers. Reactive force exerted by gel on cells explains cell movement. Finally, addition to growth medium of 0.94 M sucrose causes cluster-associated E. coli cells to become more densely packed and polymorphic. Shape is determined, in part, by neighboring cells, a novel observation to our knowledge.}, } @article {pmid30286790, year = {2018}, author = {Masenga, SK and Mweemba, M and Kachele, A and Chalubemba, Y and Toloka, P and Hamooya, BM}, title = {Lessons from a comparison of immuno-chromatographic and chemiluminescent micro-particle immunoassay in the diagnosis of syphilis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {701}, pmid = {30286790}, issn = {1756-0500}, mesh = {Antibodies, Bacterial/*blood ; Chromatography/*standards ; Humans ; Immunoassay/*standards ; Luminescent Measurements/*standards ; Sensitivity and Specificity ; Syphilis/blood/*diagnosis ; Syphilis Serodiagnosis/methods/*standards ; Treponema pallidum/*immunology ; }, abstract = {OBJECTIVE: To synthesize lessons from comparison of results obtained from the immuno-chromatographic SD Bioline testing method and the chemiluminescent micro-particle immunoassay Architect in the diagnosis of syphilis at Livingstone Central hospital laboratory.

RESULTS: The specificity and sensitivity of SD Bioline syphilis 3.0 against the chemiluminescent immunoassay using the Architect syphilis Treponema pallidum (TP) was 85.3% and 91.3% respectively with substantial agreement between the two test methods (88%, ĸ = 0.76; p < 0.0005). We recommend further comprehensive study with a larger sample size and clinical details to ascertain the validity of our findings. We also recommend using a non-treponemal test with the current treponemal tests being used to aid diagnosis.}, } @article {pmid30286789, year = {2018}, author = {Denecker, T and Lelandais, G}, title = {Empowering the detection of ChIP-seq "basic peaks" (bPeaks) in small eukaryotic genomes with a web user-interactive interface.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {698}, pmid = {30286789}, issn = {1756-0500}, support = {ANR-14-CE14-0018-02//Agence Nationale de la Recherche/ ; }, mesh = {Binding Sites ; *Chromatin Immunoprecipitation ; Computational Biology/*methods ; Eukaryota/*genetics ; Genome/*genetics ; *High-Throughput Nucleotide Sequencing ; Internet ; Protein Binding ; User-Computer Interface ; }, abstract = {OBJECTIVE: bPeaks is a peak calling program to detect protein DNA-binding sites from ChIPseq data in small eukaryotic genomes. The simplicity of the bPeaks method is well appreciated by users, but its use via an R package is challenging and time-consuming for people without programming skills. In addition, user feedback has highlighted the lack of a convenient way to carefully explore bPeaks result files. In this context, the development of a web user interface represents an important added value for expanding the bPeaks user community.

RESULTS: We developed a new bPeaks application (bPeaks App). The application allows the user to perform all the peak-calling analysis steps with bPeaks in a few mouse clicks via a web browser. We added new features relative to the original R package, particularly the possibility to import personal annotation files to compare the location of the detected peaks with specific genomic elements of interest of the user, in any organism, and a new organization of the result files which are directly manageable via a user-interactive genome browser. This significantly improves the ability of the user to explore all detected basic peaks in detail.}, } @article {pmid30286786, year = {2018}, author = {Chiwaridzo, M and Chamarime, KJ and Dambi, JM}, title = {The burden of low back pain among undergraduate physiotherapy students at the University of Zimbabwe: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {697}, pmid = {30286786}, issn = {1756-0500}, support = {D43 TW010137/TW/FIC NIH HHS/United States ; }, mesh = {Adult ; Female ; Humans ; Low Back Pain/*epidemiology ; Male ; Occupational Diseases/*epidemiology ; Physical Therapy Specialty/*education ; Prevalence ; *Students, Health Occupations ; Universities/*statistics & numerical data ; Young Adult ; Zimbabwe/epidemiology ; }, abstract = {OBJECTIVE: Globally, non-specific low back pain (NSLBP) is a common cause of morbidity in all people including physiotherapy students. However, no study has investigated the problem among undergraduate physiotherapy students in Zimbabwe. This study was conducted, therefore, to provide evidence of the prevalence, clinical characteristics and consequences of recurrent NSLBP among undergraduate physiotherapy students at the University of Zimbabwe.

RESULTS: The final sample had 90 participants, giving a study response rate of 97.8%. The median age of the participants was 22 years. The lifetime prevalence of NSLBP was 56.7% (n = 51) and the mean age of onset for NSLBP was 19.7 years (SD = 1.64 years). The 12-month prevalence of recurrent NSLBP was 38.9% (n = 35). Of the 35, 20 (57.1%) experienced at least three episodes in the last 12 months. Each episode lasted for 1-7 days in most participants (n = 31, 88.6%). The mean intensity of recurrent episodes was 3.37 (SD = 1.43) measured on Visual Analogue Scale. Only 7 (20%) experienced at least one functional limitation due to recurrent NSLBP. Additionally, only 2 (5.7%) sought medical treatment for the pain. However, 6 (17.1%) had to be absent from the university secondary to recurrent NSLBP.}, } @article {pmid30286785, year = {2018}, author = {Teka, NT and Baye, AM}, title = {Counseling practice of community pharmacists for diabetes mellitus patients in Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {700}, pmid = {30286785}, issn = {1756-0500}, mesh = {Adult ; Community Pharmacy Services/*statistics & numerical data ; Counseling/*statistics & numerical data ; Diabetes Complications/*diagnosis ; Diabetes Mellitus/*drug therapy ; Ethiopia ; Female ; Humans ; Hypoglycemic Agents/*administration & dosage ; Male ; Middle Aged ; Pharmacists/*statistics & numerical data ; }, abstract = {OBJECTIVE: Pharmacists monitor diabetic patients more often than any other healthcare providers. It is important that they have appropriate counseling practice on diabetes mellitus management. The aim of this study is to assess the counseling practice of community pharmacists for diabetes mellitus patients in Addis Ababa, Ethiopia.

RESULTS: Among 300 community pharmacy professionals, 58.3% were male. Nearly half of the community pharmacy professionals delivered appropriate counselling service on the appropriate time to administer each oral anti-diabetic drug and missed oral dose. Only 15.3% of the community pharmacy professionals gave proper counselling on the importance of continuous screening for nephropathy, retinopathy, and neuropathy.}, } @article {pmid30286725, year = {2018}, author = {Liu, H and Zhou, H and Li, Q and Peng, Q and Zhao, Q and Wang, J and Liu, X}, title = {Molecular characteristics of extended-spectrum β-lactamase-producing Escherichia coli isolated from the rivers and lakes in Northwest China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {125}, pmid = {30286725}, issn = {1471-2180}, abstract = {BACKGROUND: Extended-spectrum β-lactamases (ESBLs)-producing Escherichia coli (E. coli) isolates in environment water become progressively a potential threat to public health, while the detailed information about the ESBL-producing E. coli isolates in the rivers and lakes in Northwest China is scarce. In the present study, it was aimed to characterize the ESBL-producing E. coli isolated from the surface waters in Northwest China.

RESULTS: A total of 2686 E. coli isolates were obtained from eleven rivers and lakes in Northwest China to screen for ESBL producers. Seventy-six (2.8%) isolates were classified as ESBL producers, and phylogenic groups D and A accounted for 59.2% of the ESBL producers. CTX-Ms were the predominant ESBLs genotype, and they were represented by seven blaCTX-M subtypes. blaCTX-M-14 was the most prevalent specific CTX-M gene, followed by blaCTX-M-9, blaCTX-M-123, blaCTX-M-15, blaCTX-M-27, blaCTX-M-1 and blaCTX-M-65. Moreover, 54 of the 76 ESBL producers carried at least one plasmid-mediated quinolone resistance (PMQR) gene, and aac(6')-Ib-cr was predominant. The overall occurrence of virulence factors ranged from 1.3% (eae) to 48.7% (traT). Thirty-seven sequence types (STs) were confirmed among the 76 ESBL producers, and the predominant was ST10, which was represented by 10 isolates; importantly, clone B2-ST131, associated with severe infections in humans and animals, was detected three times.

CONCLUSION: The prevalence of ESBL-producing E. coli from the rivers and lakes in Northwest China was low (2.8%), and the extraintestinal pathogenic E. coli (ExPEC) pathotype was the most commonly detected on the basis of the virulence factor profiles. 76.3% of ESBL producers harbored more than one β-lactamase gene, and blaCTX-M-14 was the predominant genotype. Notably, one ST131 isolate from Gaogan Canal simultaneously harbored blaCTX-M-9, blaCTX-M-15, blaCTX-M-123, blaKPC-2, blaNDM-1, blaOXA-2 as well as the PMQR genes qnrA, qnrS and aac(6')-Ib-cr.}, } @article {pmid30286722, year = {2018}, author = {Mancini, MV and Damiani, C and Accoti, A and Tallarita, M and Nunzi, E and Cappelli, A and Bozic, J and Catanzani, R and Rossi, P and Valzano, M and Serrao, A and Ricci, I and Spaccapelo, R and Favia, G}, title = {Estimating bacteria diversity in different organs of nine species of mosquito by next generation sequencing.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {126}, pmid = {30286722}, issn = {1471-2180}, abstract = {BACKGROUND: Symbiosis in insects is accumulating significant amount of studies: the description of a wide array of mutualistic associations across the evolutionary history of insects suggests that resident microbiota acts as a driving force by affecting several aspects of hosts biology. Among arthropods, mosquito midgut microbiota has been largely investigated, providing crucial insights on the role and implications of host-symbiont relationships. However, limited amount of studies addressed their efforts on the investigation of microbiota colonizing salivary glands and reproductive tracts, crucial organs for pathogen invasion and vertical transmission of symbiotic microorganisms. Using 16S rRNA gene sequencing-based approach, we analysed the microbiota of gut, salivary glands and reproductive tracts of several mosquito species, representing some of the main vectors of diseases, aiming at describing the dynamics of bacterial communities within the individual.

RESULTS: We identified a shared core microbiota between different mosquito species, although interesting inter- and intra-species differences were detected. Additionally, our results showed deep divergences between genera, underlining microbiota specificity and adaptation to their host.

CONCLUSIONS: The comprehensive landscape of the bacterial microbiota components may ultimately provide crucial insights and novel targets for possible application of symbionts in innovative strategies for the control of vector borne diseases, globally named Symbiotic Control (SC), and suggesting that the holobiont of different mosquito species may significantly vary. Moreover, mosquito species are characterized by distinctive microbiota in different organs, likely reflecting different functions and/or adaptation processes.}, } @article {pmid30286721, year = {2018}, author = {Li, BJ and Jiang, DL and Meng, ZN and Zhang, Y and Zhu, ZX and Lin, HR and Xia, JH}, title = {Genome-wide identification and differentially expression analysis of lncRNAs in tilapia.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {729}, pmid = {30286721}, issn = {1471-2164}, support = {No.31572612//National Natural Science Foundation of China/ ; 2017A030303008//Science and Technology Planning Project of Guangdong Province, China/ ; No. 201803020043//Science and Technology Program of Guangzhou, China/ ; }, mesh = {Animals ; *Gene Expression Profiling ; *Genomics ; Organ Specificity ; RNA, Long Noncoding/*genetics ; RNA, Messenger/genetics ; Stress, Physiological/genetics ; Tilapia/*genetics/physiology ; }, abstract = {BACKGROUND: Long noncoding RNAs (LncRNAs) play important roles in fundamental biological processes. However, knowledge about the genome-wide distribution and stress-related expression of lncRNAs in tilapia is still limited.

RESULTS: Genome-wide identification of lncRNAs in the tilapia genome was carried out in this study using bioinformatics tools. 103 RNAseq datasets that generated in our laboratory or collected from NCBI database were analyzed. In total, 72,276 high-confidence lncRNAs were identified. The averaged positive correlation coefficient (r_mean = 0.286) between overlapped lncRNA and mRNA pairs showed significant differences with the values for all lncRNA-mRNA pairs (r_mean = 0.176, z statistics = - 2.45, p value = 0.00071) and mRNA-mRNA pairs (r_mean = 0.186, z statistics = - 2.23, p value = 0.0129). Weighted correlation network analysis of the lncRNA and mRNA datasets from 12 tissues identified 21 modules and many interesting mRNA genes that clustered with lncRNAs. Overrepresentation test indicated that these mRNAs enriched in many biological processes, such as meiosis (p = 0.00164), DNA replication (p = 0.00246), metabolic process (p = 0.000838) and in molecular function, e.g., helicase activity (p = 0.000102) and catalytic activity (p = 0.0000612). Differential expression (DE) analysis identified 99 stress-related lncRNA genes and 1955 tissue-specific DE lncRNA genes. MiRNA-lncRNA interaction analysis detected 72,267 lncRNAs containing motifs with sequence complementary to 458 miRNAs.

CONCLUSIONS: This study provides an invaluable resource for further studies on molecular bases of lncRNAs in tilapia genomes. Further function analysis of the lncRNAs will help to elucidate their roles in regulating stress-related adaptation in tilapia.}, } @article {pmid30286719, year = {2018}, author = {Yang, M and Xu, Z and Zhao, W and Liu, Q and Li, Q and Lu, L and Liu, R and Zhang, X and Cui, F}, title = {Rice stripe virus-derived siRNAs play different regulatory roles in rice and in the insect vector Laodelphax striatellus.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {219}, pmid = {30286719}, issn = {1471-2229}, support = {2017YFD0200406, 2016YFC1200603, 2017YFD0200904//National Key Plan for Scientific Research and Development of China/ ; XDB11040000, XDB11050000//Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)/ ; 2016ZX08010001//Ministry of Agriculture transgenic major projects/ ; NSFC 91540116, 31772162, 31472051, 31471782//Natural Science Foundation of China/ ; Chinese IPM 1801, Chinese IPM 1605//Open Research Fund Program of State Key Laboratory of Integrated Management of Pest Insects and Rodents/ ; }, mesh = {Animals ; Gene Expression Regulation, Plant ; Gene Ontology ; Hemiptera/genetics/virology ; Host-Pathogen Interactions/*genetics ; Insect Proteins/genetics ; Insect Vectors/genetics/*virology ; Oryza/genetics/*virology ; Plant Diseases/virology ; Plant Proteins/genetics/metabolism ; RNA, Small Interfering/*genetics ; RNA, Viral ; Tenuivirus/*genetics/pathogenicity ; }, abstract = {BACKGROUND: Most plant viruses depend on vector insects for transmission. Upon viral infection, virus-derived small interfering RNAs (vsiRNAs) can target both viral and host transcripts. Rice stripe virus (RSV) is a persistent-propagative virus transmitted by the small brown planthopper (Laodelphax striatellus, Fallen) and can cause a severe disease on rice.

RESULTS: To investigate how vsiRNAs regulate gene expressions in the host plant and the insect vector, we analyzed the expression profiles of small RNAs (sRNAs) and mRNAs in RSV-infected rice and RSV-infected planthopper. We obtained 88,247 vsiRNAs in rice that were predominantly derived from the terminal regions of the RSV RNA segments, and 351,655 vsiRNAs in planthopper that displayed relatively even distributions on RSV RNA segments. 38,112 and 80,698 unique vsiRNAs were found only in rice and planthopper, respectively, while 14,006 unique vsiRNAs were found in both of them. Compared to mock-inoculated rice, 273 genes were significantly down-regulated genes (DRGs) in RSV-infected rice, among which 192 (70.3%) were potential targets of vsiRNAs based on sequence complementarity. Gene ontology (GO) analysis revealed that these 192 DRGs were enriched in genes involved in kinase activity, carbohydrate binding and protein binding. Similarly, 265 DRGs were identified in RSV-infected planthoppers, among which 126 (47.5%) were potential targets of vsiRNAs. These planthopper target genes were enriched in genes that are involved in structural constituent of cuticle, serine-type endopeptidase activity, and oxidoreductase activity.

CONCLUSIONS: Taken together, our results reveal that infection by the same virus can generate distinct vsiRNAs in different hosts to potentially regulate different biological processes, thus reflecting distinct virus-host interactions.}, } @article {pmid30286716, year = {2018}, author = {Zhang, S and Yang, R and Huo, Y and Liu, S and Yang, G and Huang, J and Zheng, C and Wu, C}, title = {Expression of cotton PLATZ1 in transgenic Arabidopsis reduces sensitivity to osmotic and salt stress for germination and seedling establishment associated with modification of the abscisic acid, gibberellin, and ethylene signalling pathways.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {218}, pmid = {30286716}, issn = {1471-2229}, support = {31471425//National Natural Science Foundation of China/ ; ZR2015CM002//Natural Science Foundation of Shandong Province/ ; }, mesh = {Abscisic Acid/metabolism ; Arabidopsis/genetics/*physiology ; Ethylenes/metabolism ; Gene Expression Regulation, Plant ; Gibberellins/genetics/metabolism ; Gossypium/*genetics ; Osmotic Pressure/*physiology ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; Salt Tolerance/genetics ; Seedlings/genetics ; Signal Transduction ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Zinc-finger transcription factors play central roles in plant growth, development and abiotic stress responses. PLATZ encodes a class of plant-specific zinc-finger transcription factor. However, biological functions or physiological mechanism controlled by PLATZ are currently limited.

RESULTS: GhPLATZ1 transcripts were considerably up-regulated by NaCl, mannitol, abscisic acid (ABA) and gibberellin (GA) treatments. Transgenic Arabidopsis by ectopic expression of GhPLATZ1 exhibited faster seed germination and higher seedling establishment under salt and mannitol stresses than those of wild type (WT), indicating enhanced osmotic insensitivity in GhPLATZ1 transgenic Arabidopsis. The ABA content in dry seeds of GhPLATZ1 transgenic Arabidopsis was lower than that of WT whereas the ABA content was not changed in germinating seeds under salt stress. Seed germination was faster than but the seedling establishment of transgenic Arabidopsis was similar to WT. Besides, GhPLATZ1 transgenic and WT Arabidopsis exhibited insensitivity to paclobutrazol (PAC), a GA biosynthesis inhibitor, whereas exogenous GA could eliminate the growth difference between GhPLATZ1 transgenic and WT Arabidopsis under salt stress. Moreover, exogenous 1-aminocyclopropane-1-carboxylic acid (ACC), an ethylene precursor, exerted similar effects to GA. Furthermore, ABI4 and ETO1 transcripts were significantly down-regulated, whereas ACS8 was up-regulated in GhPLATZ1 transgenic Arabidopsis under salt stress.

CONCLUSIONS: In conclusion, GhPLATZ1 had broad influence in responses to salt and mannitol stresses in transgenic Arabidopsis during seed germination and seedling establishment. The effect of GhPLATZ1 expression in transgenic Arabidopsis might be mediated by the ABA, GA, and ethylene pathways. Thus, this study provided new insights into the regulatory network in response to abiotic stresses in plants.}, } @article {pmid30286715, year = {2018}, author = {Li, D and Qiao, H and Qiu, W and Xu, X and Liu, T and Jiang, Q and Liu, R and Jiao, Z and Zhang, K and Bi, L and Chen, R and Kan, Y}, title = {Identification and functional characterization of intermediate-size non-coding RNAs in maize.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {730}, pmid = {30286715}, issn = {1471-2164}, support = {31172158//National Natural Science Foundation of China/ ; 31100938//National Natural Science Foundation of China/ ; 112102110158//Scientific and Technological Projects of Henan Province/ ; YESS 20150026//Young Elite Scientist Sponsorship Program by China Association for Science and Technology/ ; }, mesh = {Conserved Sequence ; Gene Expression Profiling ; Organ Specificity ; RNA, Untranslated/*genetics ; Seedlings/growth & development ; Species Specificity ; Stress, Physiological/genetics ; Zea mays/*genetics/growth & development/physiology ; }, abstract = {BACKGROUND: The majority of eukaryote genomes can be actively transcribed into non-coding RNAs (ncRNAs), which are functionally important in development and evolution. In the study of maize, an important crop for both humans and animals, aside from microRNAs and long non-coding RNAs, few studies have been conducted on intermediate-size ncRNAs.

RESULTS: We constructed a homogenized cDNA library of 50-500 nt RNAs in the maize inbred line Chang 7-2. Sequencing revealed 169 ncRNAs, which contained 58 known and 111 novel ncRNAs (including 70 snoRNAs, 27 snRNAs, 13 unclassified ncRNAs and one tRNA). Forty of the novel ncRNAs were specific to the Panicoideae, and 24% of them are located on sense-strand of the 5' or 3' terminus of protein coding genes on chromosome. Target site analysis found that 22 snoRNAs can guide to 38 2'-O-methylation and pseudouridylation modification sites of ribosomal RNAs and small nuclear RNAs. Expression analysis showed that 43 ncRNAs exhibited significantly altered expression in different tissues or developmental stages of maize seedlings, eight ncRNAs had tissue-specific expression and five ncRNAs were strictly accumulated in the early stage of leaf development. Further analysis showed that 3 of the 5 stage-specific ncRNAs (Zm-3, Zm-18, and Zm-73) can be highly induced under drought and salt stress, while one snoRNA Zm-8 can be repressed under PEG-simulated drought condition.

CONCLUSIONS: We provided a genome-wide identification and functional analysis of ncRNAs with a size range of 50-500 nt in maize. 111 novel ncRNAs were cloned and 40 ncRNAs were determined to be specific to Panicoideae. 43 ncRNAs changed significantly during maize development, three ncRNAs can be strongly induced under drought and salt stress, suggesting their roles in maize stress response. This work set a foundation for further study of intermediate-size ncRNAs in maize.}, } @article {pmid30286713, year = {2018}, author = {Topa, H and Honkela, A}, title = {GPrank: an R package for detecting dynamic elements from genome-wide time series.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {367}, pmid = {30286713}, issn = {1471-2105}, support = {294050//Academy of Finland/ ; 259440//Academy of Finland/ ; 310261//Academy of Finland/ ; }, mesh = {Genetic Variation/*genetics ; Genome/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Sequence Analysis, DNA/methods ; Software ; }, abstract = {BACKGROUND: Genome-wide high-throughput sequencing (HTS) time series experiments are a powerful tool for monitoring various genomic elements over time. They can be used to monitor, for example, gene or transcript expression with RNA sequencing (RNA-seq), DNA methylation levels with bisulfite sequencing (BS-seq), or abundances of genetic variants in populations with pooled sequencing (Pool-seq). However, because of high experimental costs, the time series data sets often consist of a very limited number of time points with very few or no biological replicates, posing challenges in the data analysis.

RESULTS: Here we present the GPrank R package for modelling genome-wide time series by incorporating variance information obtained during pre-processing of the HTS data using probabilistic quantification methods or from a beta-binomial model using sequencing depth. GPrank is well-suited for analysing both short and irregularly sampled time series. It is based on modelling each time series by two Gaussian process (GP) models, namely, time-dependent and time-independent GP models, and comparing the evidence provided by data under two models by computing their Bayes factor (BF). Genomic elements are then ranked by their BFs, and temporally most dynamic elements can be identified.

CONCLUSIONS: Incorporating the variance information helps GPrank avoid false positives without compromising computational efficiency. Fitted models can be easily further explored in a browser. Detection and visualisation of temporally most active dynamic elements in the genome can provide a good starting point for further downstream analyses for increasing our understanding of the studied processes.}, } @article {pmid30286712, year = {2018}, author = {Fostowicz-Frelik, Ł and Li, Q and Ni, X}, title = {Oldest ctenodactyloid tarsals from the Eocene of China and evolution of locomotor adaptations in early rodents.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {150}, pmid = {30286712}, issn = {1471-2148}, support = {2015/18/E/NZ8/00637//Narodowe Centrum Nauki/International ; 41572013//National Natural Science Foundation of China/International ; XDPB05//Strategic Priority Research Program of the Chinese Academy of Sciences/International ; }, mesh = {Acclimatization ; Adaptation, Physiological ; Animals ; *Biological Evolution ; Bone and Bones/anatomy & histology ; China ; *Fossils ; Mammals ; Phylogeny ; Principal Component Analysis ; Rodentia/*anatomy & histology/classification/*genetics/physiology ; }, abstract = {BACKGROUND: Tamquammys has been considered one of the basal ctenodactyloid rodents, which has been documented in the earliest to middle Eocene (~ 56.0-48.5 Ma) in China. It was the most abundant and widespread rodent genus in the Erlian Basin (Nei Mongol, China) and dominated Arshantan small-mammal faunas of that region. Here for the first time we describe the morphology of the astragalocalcaneal complex in Tamquammys robustus (larger) and T. wilsoni, and interpret it against the background of locomotor adaptations of basal Euarchontoglires (rodents, lagomorphs, tree shrews, and primates).

RESULTS: The comparative morphology of the tarsal elements in Tamquammys robustus and T. wilsoni shows overall slenderness of the bones and their similarity to the tarsal elements of Rattus, a generalist species, and those of small rock squirrels (e.g. Sciurotamias). The two species differ slightly in their cursorial ability; smaller T. wilsoni shows some adaptations to climbing. The results of principal component analysis of the calcaneus and astragalus support this observation and place T. robustus in-between Rattus and ground/rock squirrel morphospace, and T. wilsoni closer to euarchontans, Tupaia and Purgatorius.

CONCLUSIONS: The morphology of the tarsal elements in Tamquammys indicates a generalist rodent morphotype with no particular adaptations to arboreality. We suggest that Tamquammys as a basal ctenodactyloid is closer to the ancestral astragalocalcaneal morphology of rodents than that of more derived North American paramyines of similar age. Overall similarity in Tamquammys tarsal elements structure to Purgatorius, a basal primate, may point to the antiquity of the tarsal structure in Tamquammys and a generally unspecialized foot structure in early Euarchontoglires.}, } @article {pmid30286711, year = {2018}, author = {Helm, C and Bok, MJ and Hutchings, P and Kupriyanova, E and Capa, M}, title = {Developmental studies provide new insights into the evolution of sense organs in Sabellariidae (Annelida).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {149}, pmid = {30286711}, issn = {1471-2148}, support = {ES-TAF-7033//Synthesys/International ; HE 7224/2-1//Deutsche Forschungsgemeinschaft/International ; RYC-2016-20799//Ramon y Cajal program/International ; P30 ES007033/ES/NIEHS NIH HHS/United States ; 70184215//Norwegian Taxonomy Initiative/International ; BB/P011357/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 248799//Norges Forskningsråd/International ; }, mesh = {Animals ; Larva/growth & development ; Microscopy, Confocal ; Neurons/metabolism ; Neuropeptides/metabolism ; Polychaeta/classification/growth & development/*ultrastructure ; Sense Organs/anatomy & histology/metabolism/*ultrastructure ; }, abstract = {BACKGROUND: Sabellarids, also known as honeycomb or sandcastle worms, when building their tubes, produce chemical signals (free fatty acids) that are responsible for larval settlement and the formation of three-dimensional aggregations. The larval palps and the dorsal hump (becoming the median organ in adults) are presumed to participate in such a substrate selection during settlement. Notably, the sabellariid median organ is an apparently unique organ among annelids that has been attributed with a sensory function and perhaps with some affinities to the nuchal organs of other polychaetes. Nevertheless, detailed investigations of this prominent character complex including ultrastructural examinations are lacking so far.

RESULTS: Our comprehensive investigations provide data about the anterior sensory organs in Sabellariidae and inform about their transformation during pelagic larval development. We used a comparative approach including immunostaining with subsequent confocal laser scanning microscopy (clsm), histological sections as well as electron microscopy in a range of larval and adult stages of two sabellariid species. We find that the neuronal innervation as well as the ultrastructure of the sabellariid ciliary structures along the median organ are highly comparable with that of nuchal organs known from other polychaetes. Furthermore, the myoinhibitory protein (MIP) - a protein known to be also involved into chemo-sensation - was detected in the region of the larval median organ. Moreover, we reveal the presence of an unusual type of photoreceptor as part of the median organ in Idanthyrsus australiensis with a corrugated sensory membrane ultrastructure unlike those observed in the segmental ocelli of other polychaetes.

CONCLUSIONS: We are describing for the first time the nuchal organ-like structures in different developmental stages of two species of Sabellariidae. The external morphology, neuronal innervation, developmental fate and ultrastructure of the newly-discovered median organ-based ciliary pits are comparable with the characteristics known for annelid nuchal organs and therefore indicate a homology of both sensory complexes. The presence of myoinhibitory peptide (MIP) in the respective region supports such a hypothesis and exhibits the possibility of an involvement of the entire sabellariid median organ complex, and in particular the prominent ciliated pits, in chemo-sensation.}, } @article {pmid30286710, year = {2018}, author = {Kluin, RJC and Kemper, K and Kuilman, T and de Ruiter, JR and Iyer, V and Forment, JV and Cornelissen-Steijger, P and de Rink, I and Ter Brugge, P and Song, JY and Klarenbeek, S and McDermott, U and Jonkers, J and Velds, A and Adams, DJ and Peeper, DS and Krijgsman, O}, title = {XenofilteR: computational deconvolution of mouse and human reads in tumor xenograft sequence data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {366}, pmid = {30286710}, issn = {1471-2105}, support = {//Wellcome Trust/United Kingdom ; 319661//FP7 Ideas: European Research Council/ ; NKI-2013-5799//KWF Kankerbestrijding/ ; }, mesh = {Animals ; Computers ; Databases, Genetic ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mice ; }, abstract = {BACKGROUND: Mouse xenografts from (patient-derived) tumors (PDX) or tumor cell lines are widely used as models to study various biological and preclinical aspects of cancer. However, analyses of their RNA and DNA profiles are challenging, because they comprise reads not only from the grafted human cancer but also from the murine host. The reads of murine origin result in false positives in mutation analysis of DNA samples and obscure gene expression levels when sequencing RNA. However, currently available algorithms are limited and improvements in accuracy and ease of use are necessary.

RESULTS: We developed the R-package XenofilteR, which separates mouse from human sequence reads based on the edit-distance between a sequence read and reference genome. To assess the accuracy of XenofilteR, we generated sequence data by in silico mixing of mouse and human DNA sequence data. These analyses revealed that XenofilteR removes > 99.9% of sequence reads of mouse origin while retaining human sequences. This allowed for mutation analysis of xenograft samples with accurate variant allele frequencies, and retrieved all non-synonymous somatic tumor mutations.

CONCLUSIONS: XenofilteR accurately dissects RNA and DNA sequences from mouse and human origin, thereby outperforming currently available tools. XenofilteR is open source and available at https://github.com/PeeperLab/XenofilteR .}, } @article {pmid30285911, year = {2018}, author = {Asem, MD and Shi, L and Jiao, JY and Wang, D and Han, MX and Dong, L and Liu, F and Salam, N and Li, WJ}, title = {Desertimonas flava gen. nov., sp. nov. isolated from a desert soil, and proposal of Ilumatobacteraceae fam. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3593-3599}, doi = {10.1099/ijsem.0.003038}, pmid = {30285911}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; *Desert Climate ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A non-motile, coccobacilli-shaped and yellow-coloured bacterium, designated strain SYSU D60003T, was isolated from a desert soil sample. Cells were Gram-stain-positive, catalase-negative and oxidase-positive. The whole cell hydrolysates contained ll-diaminopimelic acid as the diagnostic amino acid. The major fatty acids were C16 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and iso-C16 : 0. The respiratory menaquinones were MK-9(H8), MK-9(H4) and MK-9(H6). The DNA G+C content was determined to be 70.2 % (genome). The polar lipids detected were diphosphatidylglycerol, an unidentified glycolipid and seven unidentified polar lipids. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain SYSU D60003T belonged to the order Acidimicrobiales (class Acidimicrobiia), but formed a clade closely linked to members of the genus Ilumatobacter. Data from a polyphasic taxonomy study suggested that the isolate represents a novel species of a novel genus in the order Acidimicrobiales, for which the name Desertimonas flava gen. nov., sp. nov. is proposed. The type strain of the proposed new taxon is SYSU D60003T (=KCTC 39917T=NBRC 112924T). Additionally, the new taxon along with the genus Ilumatobater (family unassigned) were distinctly separated from the related families Acidimicrobiaceae, Iamiaceae and 'Microtrichaceae' in the phylogenetic trees, besides presenting a unique 16S rRNA gene signature nucleotides. Therefore, we propose a new family Ilumatobacteraceae fam. nov. within the order Acidimicrobiales to accommodate members of these two genera.}, } @article {pmid30285910, year = {2018}, author = {Feng, Y and Stams, AJM and Sánchez-Andrea, I and de Vos, WM}, title = {Eubacterium maltosivorans sp. nov., a novel human intestinal acetogenic and butyrogenic bacterium with a versatile metabolism.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.003028}, pmid = {30285910}, issn = {1466-5034}, abstract = {A novel anaerobic, non-spore-forming bacterium was isolated from a faecal sample of a healthy adult. The isolate, designated strain YIT, was cultured in a basal liquid medium under a gas phase of H2/CO2 supplemented with yeast extract (0.1 g l-1). Cells of strain YIT were short rods (0.4-0.7×2.0-2.5 µm), appearing singly or in pairs, and stained Gram-positive. Catalase activity and gelatin hydrolysis were positive while oxidase activity, indole formation, urease activity and aesculin hydrolysis were negative. Growth was observed within a temperature range of 20-45 °C (optimum, 35-37 °C), and a pH range of 5.0-8.0 (optimum pH 7.0-7.5). Doubling time was 2.3 h when grown with glucose at pH 7.2 and 37 °C. Besides acetogenic growth, the isolate was able to ferment a large range of monomeric sugars with acetate and butyrate as the main end products. Strain YIT did not show respiratory growth with sulfate, sulfite, thiosulfate or nitrate as electron acceptors. The major cellular fatty acids of the isolate were C16 : 0 and C18 : 0. The genomic DNA G+C content was 47.8 mol%. Strain YIT is affiliated to the genus Eubacterium, sharing highest levels of 16S rRNA gene similarity with Eubacterium limosum ATCC 8486T (97.3 %), Eubacterium callanderi DSM 3662T (97.5 %), Eubacterium aggregans DSM 12183T (94.4 %) and Eubacterium barkeri DSM 1223T (94.8 %). Considering its physiological and phylogenetic characteristics, strain YIT represents a novel species within the genus Eubacterium, for which the name Eubacterium maltosivorans sp. nov. is proposed. The type strain is YIT (=DSM 105863T=JCM 32297T).}, } @article {pmid30285909, year = {2018}, author = {Cho, HY and Heo, J and Hong, SB and Kim, JS and Kwon, SW and Kim, SJ}, title = {Corrigendum: Simplicispira suum sp. nov., isolated from a dust collector at a pig farm.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3377}, doi = {10.1099/ijsem.0.002979}, pmid = {30285909}, issn = {1466-5034}, } @article {pmid30285907, year = {2018}, author = {Mekonnen, HS and Azagew, AW}, title = {Non-adherence to anti-tuberculosis treatment, reasons and associated factors among TB patients attending at Gondar town health centers, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {691}, pmid = {30285907}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Antitubercular Agents/*administration & dosage ; Ethiopia ; Female ; Humans ; Male ; Medication Adherence/*statistics & numerical data ; Middle Aged ; Tuberculosis/*drug therapy ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to assess the prevalence of non-adherence to anti-tuberculosis treatment, reasons and associated factors among TB patients attending at Gondar town health centers.

RESULT: A total of 314 participants were included with the response rate of 97.5%. The mean age of participants was 35.94 (SD ± 13.83) years. The overall rate of non-adherence to anti-TB treatment was 21.2% (95% CI 17.2, 26.1). Continuation phase of treatment (AOR = 2.27, 95% CI (1.54, 5.94)), presence of more than one co-morbidity (AOR = 6.22; 95% CI (2.21, 17.48)), poor knowledge about TB and anti-TB therapy (AOR = 4.11; 95% CI 1.57, 10.75), poor patient-provider relationship (AOR = 4.60, 95% CI 1.63, 12.97), and alcohol intake (AOR = 5.03; 95% CI 1.54, 16.40) were significantly associated with non-adherence. Forgetting 40 (23.1%), Being busy with other work 35 (20.2%), and being out of home/town 24 (13.9%) were the major reasons of participants for interruption of taking anti-TB medications.}, } @article {pmid30285899, year = {2018}, author = {Gebreyesus, LG and Aregay, AF and Gebrekidan, KG and Alemayehu, YH}, title = {Factors associated with treatment outcome of acute post streptococcal glomerulonephritis among patients less than 18 years in Mekelle City, Public Hospitals, North Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {693}, pmid = {30285899}, issn = {1756-0500}, mesh = {Acute Disease ; Adolescent ; Anti-Bacterial Agents/*therapeutic use ; Antihypertensive Agents/*therapeutic use ; Child ; Child, Preschool ; Cross-Sectional Studies ; Diuretics/*therapeutic use ; Drug Therapy, Combination ; Ethiopia/epidemiology ; Female ; Furosemide/*therapeutic use ; Glomerulonephritis/*etiology ; Humans ; Male ; Outcome Assessment (Health Care)/*statistics & numerical data ; Retrospective Studies ; Risk Factors ; Rural Population/statistics & numerical data ; Streptococcal Infections/*complications ; }, abstract = {OBJECTIVE: To assess factors associated treatment outcomes of acute post streptococcal glomerular nephritis among patients less than 18 years old in Mekelle City Public Hospitals.

RESULTS: About 334 medical records c of children with acute post streptococcal glomerular nephritis were revised during the study period. Of these 244 (73.1%) had a positive outcome. acute post streptococcal glomerular nephritis was found to be statically significant associated with age < 5 years, duration of infection, the source of infection and length of stay in Hospital.}, } @article {pmid30285897, year = {2018}, author = {Rutaro, K and Malinga, GM and Lehtovaara, VJ and Opoke, R and Nyeko, P and Roininen, H and Valtonen, A}, title = {Fatty acid content and composition in edible Ruspolia differens feeding on mixtures of natural food plants.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {687}, pmid = {30285897}, issn = {1756-0500}, support = {14956//Academy of Finland/ ; }, mesh = {Africa ; Animals ; *Diet ; *Fatty Acids, Monounsaturated ; *Fatty Acids, Omega-3 ; *Fatty Acids, Omega-6 ; *Fatty Acids, Unsaturated ; *Orthoptera ; *Plants, Edible ; }, abstract = {OBJECTIVES: To develop successful mass-rearing programs of edible insects, knowledge of the feeds and their influence on nutritional content is critical. We assessed the influence of natural food plants (grass inflorescences) and their mixtures on fatty acid profiles of edible Ruspolia differens. We reared neonate nymphs to adult on six dietary treatments consisting of one, and mixtures of two, three, five, six and eight plants.

RESULTS: The contents of saturated, monounsaturated and polyunsaturated fatty acids, omega-6/omega-3 ratio, and adult body weight did not differ among dietary treatments. However, the composition of fatty acids differed significantly among insects fed on six dietary treatments, but only for the rare fatty acids. Our results demonstrate that even if natural diets (grass inflorescences) do not strongly modify fatty acid contents or compositions of R. differens, when reared from neonate nymphs to adults, their n - 6/n - 3 fatty acid ratio is generally low and thus good for a healthy human diet.}, } @article {pmid30285895, year = {2018}, author = {Aboye, W and Berhe, T and Birhane, T and Gerensea, H}, title = {Prevalence and associated factors of low birth weight in Axum town, Tigray, North Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {684}, pmid = {30285895}, issn = {1756-0500}, mesh = {Adult ; Alcohol Drinking/*epidemiology ; Anemia/*epidemiology ; Ethiopia/epidemiology ; Female ; Humans ; *Infant, Low Birth Weight ; Infant, Newborn ; Pregnancy ; Pregnancy Complications/*epidemiology ; Prenatal Care/*statistics & numerical data ; Prevalence ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: Weight at birth is a good indicator of the newborn's chances for survival, growth, long-term health and psychosocial development. Therefore, the aimed of this study is to assess the prevalence and associated factors of low birth weight in Axum town, Tigray, North Ethiopia.

RESULT: The magnitude of low birth weight was 8.8%. Height of mother adjusted odds ratio (AOR) 4.607 (CI 1.34-15.8), gestational age AOR 4.7 (CI 1.08-20.44), anti-natal care (ANC) visit AOR 0.076 (CI 0.009-0.645), anemia during pregnancy AOR 14.5 (CI 3.821-55.6) and drinking alcohol AOR 6.4 (CI 1.235-33.94) were found to be significantly associated with low birth weight. Pre-conceptual counseling on nutrition, about the effect of short suture on birth outcome and personal maternal habit (drinking alcohol), effective treatment and prevention of anemia and awareness on the importance ANC follow up should be the target.}, } @article {pmid30285861, year = {2018}, author = {O'Neill, AM and Gallo, RL}, title = {Host-microbiome interactions and recent progress into understanding the biology of acne vulgaris.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {177}, pmid = {30285861}, issn = {2049-2618}, support = {R01 AR069653/AR/NIAMS NIH HHS/United States ; U19 AI117673/AI/NIAID NIH HHS/United States ; R01 AR064781/AR/NIAMS NIH HHS/United States ; R01 AI116576/AI/NIAID NIH HHS/United States ; }, abstract = {Acne is one of the most common skin diseases worldwide and results in major health care costs and significant morbidity to severely affected individuals. However, the pathophysiology of this disorder is not well understood. Host-microbiome interactions that affect both innate and adaptive immune homeostasis appear to be a central factor in this disease, with recent observations suggesting that the composition and activities of the microbiota in acne is perturbed. Staphylococcus epidermidis and Cutibacterium acnes (C. acnes; formerly Propionibacterium acnes) are two major inhabitants of the skin that are thought to contribute to the disease but are also known to promote health by inhibiting the growth and invasion of pathogens. Because C. acnes is ubiquitous in sebaceous-rich skin, it is typically labeled as the etiological agent of acne yet it fails to fulfill all of Koch's postulates. The outdated model of acne progression proposes that increased sebum production promotes over-proliferation of C. acnes in a plugged hair follicle, thereby driving inflammation. In contrast, growing evidence indicates that C. acnes is equally abundant in both unaffected and acne-affected follicles. Moreover, recent advances in metagenomic sequencing of the acne microbiome have revealed a diverse population structure distinct from healthy individuals, uncovering new lineage-specific virulence determinants. In this article, we review recent developments in the interactions of skin microbes with host immunity, discussing the contribution of dysbiosis to the immunobiology of acne and newly emerging skin microbiome-based therapeutics to treat acne.}, } @article {pmid30285857, year = {2018}, author = {Wu, Z and Lu, L and Du, J and Yang, L and Ren, X and Liu, B and Jiang, J and Yang, J and Dong, J and Sun, L and Zhu, Y and Li, Y and Zheng, D and Zhang, C and Su, H and Zheng, Y and Zhou, H and Zhu, G and Li, H and Chmura, A and Yang, F and Daszak, P and Wang, J and Liu, Q and Jin, Q}, title = {Comparative analysis of rodent and small mammal viromes to better understand the wildlife origin of emerging infectious diseases.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {178}, pmid = {30285857}, issn = {2049-2618}, support = {R01 AI110964/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Rodents represent around 43% of all mammalian species, are widely distributed, and are the natural reservoirs of a diverse group of zoonotic viruses, including hantaviruses, Lassa viruses, and tick-borne encephalitis viruses. Thus, analyzing the viral diversity harbored by rodents could assist efforts to predict and reduce the risk of future emergence of zoonotic viral diseases.

RESULTS: We used next-generation sequencing metagenomic analysis to survey for a range of mammalian viral families in rodents and other small animals of the orders Rodentia, Lagomorpha, and Soricomorpha in China. We sampled 3,055 small animals from 20 provinces and then outlined the spectra of mammalian viruses within these individuals and the basic ecological and genetic characteristics of novel rodent and shrew viruses among the viral spectra. Further analysis revealed that host taxonomy plays a primary role and geographical location plays a secondary role in determining viral diversity. Many viruses were reported for the first time with distinct evolutionary lineages, and viruses related to known human or animal pathogens were identified. Phylogram comparison between viruses and hosts indicated that host shifts commonly happened in many different species during viral evolutionary history.

CONCLUSIONS: These results expand our understanding of the viromes of rodents and insectivores in China and suggest that there is high diversity of viruses awaiting discovery in these species in Asia. These findings, combined with our previous bat virome data, greatly increase our knowledge of the viral community in wildlife in a densely populated country in an emerging disease hotspot.}, } @article {pmid30285851, year = {2018}, author = {Mehrshad, M and Salcher, MM and Okazaki, Y and Nakano, SI and Šimek, K and Andrei, AS and Ghai, R}, title = {Hidden in plain sight-highly abundant and diverse planktonic freshwater Chloroflexi.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {176}, pmid = {30285851}, issn = {2049-2618}, abstract = {BACKGROUND: Representatives of the phylum Chloroflexi, though reportedly highly abundant in the extensive deep water habitats of both marine (SAR202 up to 30% of total prokaryotes) and freshwater (CL500-11 up to 26% of total prokaryotes), remain uncultivated and uncharacterized. There are few metagenomic studies on marine Chloroflexi representatives, while the pelagic freshwater Chloroflexi community is largely unknown except for a single metagenome-assembled genome of CL500-11.

RESULTS: Here, we provide the first extensive examination of the community composition of this cosmopolitan phylum in a range of pelagic habitats (176 datasets) and highlight the impact of salinity and depth on their phylogenomic composition. Reconstructed genomes (53 in total) provide a perspective on the phylogeny, metabolism, and distribution of three novel classes and two family-level taxa within the phylum Chloroflexi. We unraveled a remarkable genomic diversity of pelagic freshwater Chloroflexi representatives that thrive not only in the hypolimnion as previously suspected, but also in the epilimnion. Our results suggest that the lake hypolimnion provides a globally stable habitat reflected in lower species diversity among hypolimnion-specific CL500-11 and TK10 clusters in distantly related lakes compared to a higher species diversity of the epilimnion-specific SL56 cluster. Cell volume analyses show that the CL500-11 are among the largest prokaryotic cells in the water column of deep lakes and with a biomass to abundance ratio of two they significantly contribute to the deep lake carbon flow. Metabolic insights indicate participation of JG30-KF-CM66 representatives in the global cobalamin production via cobinamide to cobalamin salvage pathway.

CONCLUSIONS: Extending phylogenomic comparisons to brackish and marine habitats suggests salinity as the major influencer of the community composition of the deep-dwelling Chloroflexi in marine (SAR202) and freshwater (CL500-11) habitats as both counterparts thrive in intermediate brackish salinity; however, freshwater habitats harbor the most phylogenetically diverse community of pelagic Chloroflexi representatives that reside both in epi- and hypolimnion.}, } @article {pmid30285846, year = {2018}, author = {Xiong, C and Wen, Z and Yu, J and Chen, J and Liu, CP and Zhang, X and Chen, P and Xu, RM and Li, G}, title = {UBN1/2 of HIRA complex is responsible for recognition and deposition of H3.3 at cis-regulatory elements of genes in mouse ES cells.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {110}, pmid = {30285846}, issn = {1741-7007}, support = {55008737/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {BACKGROUND: H3.3 is an ancient and conserved H3 variant and plays essential roles in transcriptional regulation. HIRA complex, which is composed of HIRA, UBN1 or UBN2, and Cabin1, is a H3.3 specific chaperone complex. However, it still remains largely uncharacterized how HIRA complex specifically recognizes and deposits H3.3 to the chromatin, such as promoters and enhancers.

RESULTS: In this study, we demonstrate that the UBN1 or UBN2 subunit is mainly responsible for specific recognition and direct binding of H3.3 by the HIRA complex. While the HIRA subunit can enhance the binding affinity of UBN1 toward H3.3, Cabin1 subunit cannot. We also demonstrate that both Ala87 and Gly90 residues of H3.3 are required and sufficient for the specific recognition and binding by UBN1. ChIP-seq studies reveal that two independent HIRA complexes (UBN1-HIRA and UBN2-HIRA) can cooperatively deposit H3.3 to cis-regulatory regions, including active promoters and active enhancers in mouse embryonic stem (mES) cells. Importantly, disruption of histone chaperone activities of UBN1 and UBN2 by FID/AAA mutation results in the defect of H3.3 deposition at promoters of developmental genes involved in neural differentiation, and subsequently causes the failure of activation of these genes during neural differentiation of mES cells.

CONCLUSION: Together, our results provide novel insights into the mechanism by which the HIRA complex specifically recognizes and deposits H3.3 at promoters and enhancers of developmental genes, which plays a critical role in neural differentiation of mES cells.}, } @article {pmid30285843, year = {2018}, author = {Ziganshina, EE and Mohammed, WS and Shagimardanova, EI and Shigapova, LH and Ziganshin, AM}, title = {Draft genome sequence of Staphylococcus sp. EZ-P03 isolated from a mesophilic anaerobic digester.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {694}, pmid = {30285843}, issn = {1756-0500}, support = {16-34-60093//Russian Foundation for Basic Research/ ; }, mesh = {Animals ; Chickens ; DNA, Bacterial/*genetics ; Databases, Genetic ; *Firmicutes ; Genome, Bacterial/*genetics ; Manure/*microbiology ; RNA, Ribosomal, 16S/*genetics ; Staphylococcus/*genetics ; }, abstract = {OBJECTIVES: Staphylococcus species of the family Staphylococcaceae are facultatively anaerobic Gram-positive cocci growing in clusters, pairs and occasionally in short chains. Staphylococci can be detected in different environments. They are common commensals, but some can also cause infections in humans. Hence, their investigation is required to understand ecology and genetics and to create an opportunity for comparative studies.

DATA DESCRIPTION: In this study, we report the determination of a draft genome sequence of Staphylococcus sp. strain EZ-P03 which was isolated from anaerobically digested chicken waste materials. The draft genome of Staphylococcus sp. EZ-P03 constituted a total of 62 contigs (> 500 bp) amounting to 2,689,358 bp with a G+C content of 37.3% and a N50 contig size of 126,562 bp. The whole genome shotgun project of Staphylococcus sp. strain EZ-P03 has been deposited at DDBJ/ENA/GenBank under the accession number QPMO00000000.}, } @article {pmid30285840, year = {2018}, author = {Carroll, P and Muwanguzi-Karugaba, J and Parish, T}, title = {Codon-optimized DsRed fluorescent protein for use in Mycobacterium tuberculosis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {685}, pmid = {30285840}, issn = {1756-0500}, support = {OPP42786//Bill and Melinda Gates Foundation/ ; }, mesh = {*Codon ; *Genes, Reporter ; *Luminescent Proteins ; *Mycobacterium tuberculosis ; }, abstract = {OBJECTIVE: We have previously codon-optimized a number of red fluorescent proteins for use in Mycobacterium tuberculosis (mCherry, tdTomato, Turbo-635). We aimed to expand this repertoire to include DsRed, another widely used and flexible red fluorescent protein.

RESULTS: We generated expression constructs with a full length DsRed under the control of one of three strong, constitutive promoters (Phsp60, PrpsA or PG13) for use in mycobacteria. We confirmed that full length DsRed (225 amino acids) was expressed and fluoresced brightly. In contrast to mCherry, truncated versions of DsRed lacking several amino acids at the N-terminus were not functional. Thus, we have expanded the repertoire of optimized fluorescent proteins for mycobacteria.}, } @article {pmid30285838, year = {2018}, author = {Mohd Hanafiah, K and Garcia, ML and Barnes, NC and Anderson, DA}, title = {Detection of virus-specific polymeric immunoglobulin A in acute hepatitis A, C, E virus serum samples using novel chimeric secretory component.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {688}, pmid = {30285838}, issn = {1756-0500}, mesh = {Biomarkers/blood ; Hepatitis A/*blood ; Hepatitis Antibodies/*blood ; Hepatitis C/*blood ; Hepatitis E/*blood ; Humans ; Immunoglobulin A/*analysis ; Proof of Concept Study ; Serologic Tests/*standards ; }, abstract = {OBJECTIVE: To conduct a proof-of-concept study on preferential binding of polymeric IgA (pIgA) using a novel recombinant rabbit/human chimeric secretory component (cSC) and preliminary assessment of the diagnostic potential of virus-specific pIgA in discriminating acute hepatitis A, E, and C (HAV, HEV, HCV) patients and uninfected controls using an indirect enzyme-linked immunoassay.

RESULTS: cSC binds > 0.06 μg/ml of purified human and mouse pIgA with negligible cross-reactivity against IgM and IgA. Virus-specific pIgA was significantly higher in serum of acute HAV (n = 6) and HEV (n = 12) patients than uninfected samples (HEV: p < 0.001; HAV: p = 0.001), and had low correlation with virus-specific IgM (HEV r: - 0.25, 95% CI - 0.88 to 0.71, p = 0.636; HAV r: 0.05, 95% CI - 0.54 to 0.60, p: 0.885). Anti-HCV pIgA peaked early in HCV seroconversion panels (n = 14), and was undetectable after 4 weeks post-primary bleed, even in ongoing infections, while serum anti-HCV IgA, IgG and IgM persisted. Patients with early acute HCV infection had significantly higher levels of anti-HCV pIgA compared to those with chronic infections (p < 0.01). The use of novel cSC demonstrates the presence of virus-specific pIgA in sera of patients with acute HAV, HEV, and HCV infection, and posits its potential utility as a diagnostic biomarker that warrants further validation on larger sample populations.}, } @article {pmid30285836, year = {2018}, author = {Thakur, M and Chandra, K and Sahajpal, V and Samanta, A and Sharma, A and Mitra, A}, title = {Functional validation of human-specific PowerPlex® 21 System (Promega, USA) in chimpanzee (Pan troglodytes).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {695}, pmid = {30285836}, issn = {1756-0500}, mesh = {Animals ; DNA Fingerprinting/*standards ; Female ; Genetic Loci/*genetics ; Genetics, Population ; Humans ; Male ; Microsatellite Repeats/*genetics ; Pan troglodytes/*genetics ; Reproducibility of Results ; }, abstract = {OBJECTIVE: This study was aimed to test the PowerPlex® 21 System (Promega, USA), used for human identification applications for its positive cross-species applicability in Chimpanzees (Pan troglodytes) in order to identify heterologous STRs which can be used for individual identification, paternity testing, relatedness establishment and reconstruction of pedigrees and studbook records for captive and wild chimpanzee breeding populations.

RESULTS: Of 21 STRs in PowerPlex® 21 System (Promega, USA), 19 loci amplified and found to be polymorphic. Locus Aml showed differential banding patterns in males and females similar to those seen for humans and correctly assigned sexes of known identity. Altogether, 58 different alleles were found with an average 3.05 ± 0.28 alleles per locus. Mean observed (Ho), and expected heterozygosity (He) were 0.93 ± 0.03 and 0.52 ± 0.05, respectively.}, } @article {pmid30285833, year = {2018}, author = {Alemu, G and Jemal, A and Zerdo, Z}, title = {Intestinal parasitosis and associated factors among diabetic patients attending Arba Minch Hospital, Southern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {689}, pmid = {30285833}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Comorbidity ; Cross-Sectional Studies ; Diabetes Mellitus/*epidemiology ; Ethiopia/epidemiology ; Female ; Humans ; Intestinal Diseases, Parasitic/*epidemiology ; Male ; Middle Aged ; Opportunistic Infections/*epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Local assessment of the magnitude of intestinal parasitic infections and associated factors among diabetic patients helps for good prognosis of diabetes. Hospital based cross-sectional study was conducted by recruiting 215 diabetic patients. A structured questionnaire was used to capture data about socio-demographic characteristics, clinical history and factors associated with intestinal parasitosis. Stool samples were collected and processed by direct wet mount, formol-ether concentration and modified ziehl-Neelson staining techniques. All data were analyzed using Statistical Package for Social Sciences software version 20.

RESULTS: The rate of intestinal parasitic infection among diabetic patients was 19.5%. Cryptosporidium parvum accounts the highest frequency (18, 8.4%) followed by Ascaris lumbricoides (8, 3.7%). Presence of domestic animals in the house (AOR = 2.857, 95% CI 1.290-6.330, p = 0.010), manifestation of abdominal pain (AOR = 3.716, 95% CI 1.632-8.459, p = 0.002) and farmer and labor occupation (AOR = 3.695, 95% CI 1.082-12.618, p = 0.037) were significantly associated with intestinal parasitosis. The magnitude of intestinal parasitosis among diabetic patients attending Arba Minch Hospital was considerable. Hence, we recommend routine screening and prompt treatment for intestinal parasitosis in order to improve the health of diabetic patients.}, } @article {pmid30285831, year = {2018}, author = {Chessman, J and Patterson, J and Nippita, T and Drayton, B and Ford, J}, title = {Haemoglobin concentration following postpartum haemorrhage and the association between blood transfusion and breastfeeding: a retrospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {686}, pmid = {30285831}, issn = {1756-0500}, support = {APP1094822//National Health and Medical Research Council/ ; FT120100069//Australian Research Council Future Fellowship/ ; }, mesh = {Adolescent ; Adult ; Breast Feeding/*statistics & numerical data ; Erythrocyte Transfusion/*statistics & numerical data ; Female ; Humans ; New South Wales/epidemiology ; Postpartum Hemorrhage/*blood/*therapy ; Pregnancy ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to determine the association between red blood cell transfusion and breastfeeding among women who have suffered a postpartum haemorrhage at birth taking into account post-birth haemoglobin concentrations.

RESULTS: Among 15,451 maternities with postpartum haemorrhage in New South Wales public hospitals between 2007 and 2010, 1828 (12%) received a red cell transfusion. Among transfused women, 686 (38%) had haemoglobin concentration pre-transfusion < 70 g/L, 792 (43%) had 70-90 g/L, and 350 (19%) had > 90 g/L. Rates and adjusted relative risks (aRR) for breastfeeding at hospital discharge were as follows: for women with haemoglobin concentrations < 70 g/L following birth and received a transfusion, 78.6% were breastfeeding and the aRR of breastfeeding compared to untransfused women was 0.90 (99% confidence interval (CI) 0.86-0.95); for women with haemoglobin concentrations 70-90 g/L, 81.3% were breastfeeding, aRR 0.94 (99% CI 0.90-0.98); and for women with haemoglobin concentrations > 90 g/L, 80.9% were breastfeeding, aRR 0.94 (99% CI 0.88-1.00).}, } @article {pmid30285827, year = {2018}, author = {Grum, T and Hintsa, S and Hagos, G}, title = {Dietary factors associated with preeclampsia or eclampsia among women in delivery care services in Addis Ababa, Ethiopia: a case control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {683}, pmid = {30285827}, issn = {1756-0500}, mesh = {Adult ; Case-Control Studies ; Counseling ; Diet/*statistics & numerical data ; Eclampsia/*epidemiology ; Ethiopia/epidemiology ; Female ; *Fruit ; Humans ; Pre-Eclampsia/*epidemiology ; Pregnancy ; Prenatal Care/*statistics & numerical data ; *Vegetables ; Young Adult ; }, abstract = {OBJECTIVE: Preeclampsia or eclampsia, which is one of the direct obstetric complication, results in maternal and child morbidity and mortality. The factors associated with it remains unclear. So, the aim of the study was to assess the dietary factors associated with preeclampsia or eclampsia among women in delivery care services in Addis Ababa, Ethiopia.

RESULTS: Factors which were investigated as protective for preeclampsia or eclampsia were: Fruit intake during pregnancy (AOR: 0.94, 95% CI 0.20, 4.32), vegetable intake during pregnancy (AOR: 0.95, 95% CI 0.01, 0.71) and receiving nutritional counseling during antenatal care (AOR: 0.17, 95% CI 0.05, 0.6). In the other side being nulliparous women was a risk factor for preeclampsia or eclampsia (AOR: 2.02, 95% CI 1.15, 3.55).}, } @article {pmid30285824, year = {2018}, author = {Parrish, KL and Hogan, PG and Clemons, AA and Fritz, SA}, title = {Spatial relationships among public places frequented by families plagued by methicillin-resistant Staphylococcus aureus.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {692}, pmid = {30285824}, issn = {1756-0500}, support = {R01 HS021736/HS/AHRQ HHS/United States ; R01-HS024269//Agency for Healthcare Research and Quality/ ; UL1-TR000448//National Center for Advancing Translational Sciences/ ; K23-AI091690//National Institutes of Allergy and Infectious Diseases/ ; R01 HS024269/HS/AHRQ HHS/United States ; K23 AI091690/AI/NIAID NIH HHS/United States ; R01-HS021736//Agency for Healthcare Research and Quality/ ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Community-Acquired Infections/*epidemiology ; Female ; *Geographic Mapping ; Humans ; Infant ; Male ; Methicillin-Resistant Staphylococcus aureus/*pathogenicity ; Middle Aged ; Missouri/epidemiology ; Soft Tissue Infections/*epidemiology ; Staphylococcal Infections/*epidemiology ; Staphylococcal Skin Infections/*epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: To understand factors associated with community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) acquisition and infection, we mapped public places (including personal service establishments, fitness centers, pools, schools, and daycares) visited by members of households affected by CA-MRSA skin and soft tissue infection.

RESULTS: From January 2012 to October 2015, households of children with CA-MRSA SSTI in metropolitan St. Louis were enrolled in the HOME: Household Observation of MRSA in the Environment study. Addresses of public places visited within 3 months of enrollment were reported by 671 participants and were analyzed using a geographic information system (GIS). The Nearest Neighbor Tool in ArcGIS assessed clustering of public places within the study region. Public places were significantly clustered within the study area compared to the expected distance between locations (p < 0.001). Additionally, one-third (48/150) of participating households visited at least one public place in common with other households. No significant relationship between participants visiting the public places within 3 months of enrollment and subsequent colonization or SSTI were found. Understanding community behavior is critical to informing public health initiatives to reduce the prevalence of CA-MRSA infections.}, } @article {pmid30285818, year = {2018}, author = {Fernandes, J and Brunton, I and Strudwick, G and Banik, S and Strauss, J}, title = {Physician experience with speech recognition software in psychiatry: usage and perspective.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {690}, pmid = {30285818}, issn = {1756-0500}, mesh = {Adult ; *Documentation ; Hospitals, Psychiatric/*statistics & numerical data ; Humans ; Medical Staff, Hospital/*statistics & numerical data ; Speech Recognition Software/*statistics & numerical data ; }, abstract = {OBJECTIVE: The purpose of this paper is to extend a previous study by evaluating the use of a speech recognition software in a clinical psychiatry milieu. Physicians (n = 55) at a psychiatric hospital participated in a limited implementation and were provided with training, licenses, and relevant devices. Post-implementation usage data was collected via the software. Additionally, a post-implementation survey was distributed 5 months after the technology was introduced.

RESULTS: In the first month, 45 out of 51 (88%) physicians were active users of the technology; however, after the full evaluation period only 53% were still active. The average active user minutes and the average active user lines dictated per month remained consistent throughout the evaluation. The use of speech recognition software within a psychiatric setting is of value to some physicians. Our results indicate a post-implementation reduction in adoption, with stable usage for physicians who remained active users. Future studies to identify characteristics of users and/or technology that contribute to ongoing use would be of value.}, } @article {pmid30285739, year = {2018}, author = {Bonin, F and Taouis, K and Azorin, P and Petitalot, A and Tariq, Z and Nola, S and Bouteille, N and Tury, S and Vacher, S and Bièche, I and Rais, KA and Pierron, G and Fuhrmann, L and Vincent-Salomon, A and Formstecher, E and Camonis, J and Lidereau, R and Lallemand, F and Driouch, K}, title = {VOPP1 promotes breast tumorigenesis by interacting with the tumor suppressor WWOX.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {109}, pmid = {30285739}, issn = {1741-7007}, abstract = {BACKGROUND: The WW domain-containing oxidoreductase (WWOX) gene, frequently altered in breast cancer, encodes a tumor suppressor whose function is mediated through its interactions with cancer-related proteins, such as the pro-apoptotic protein p73α.

RESULTS: To better understand the involvement of WWOX in breast tumorigenesis, we performed a yeast two-hybrid screen and co-immunoprecipitation assays to identify novel partners of this protein. We characterized the vesicular overexpressed in cancer pro-survival protein 1 (VOPP1) as a new regulator of WWOX. In breast cancer cells, VOPP1 sequestrates WWOX in lysosomes, impairs its ability to associate with p73α, and inhibits WWOX-dependent apoptosis. Overexpressed VOPP1 potentiates cellular transformation and enhances the growth of transplanted tumors in vivo. VOPP1 is overexpressed in breast tumors, especially in tumors that retain WWOX. Moreover, increased expression of VOPP1 is associated with reduced survival of patients with WWOX-positive, but not with WWOX-negative, tumors.

CONCLUSIONS: These findings emphasize the importance of the sequestration of WWOX by VOPP1 in addition to WWOX loss in breast tumors and define VOPP1 as a novel oncogene promoting breast carcinogenesis by inhibiting the anti-tumoral effect of WWOX.}, } @article {pmid30285730, year = {2018}, author = {Manzanedo, RD and Schanz, FR and Fischer, M and Allan, E}, title = {Fagus sylvatica seedlings show provenance differentiation rather than adaptation to soil in a transplant experiment.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {42}, pmid = {30285730}, issn = {1472-6785}, abstract = {BACKGROUND: Understanding and predicting the response of tree populations to climate change requires understanding the pattern and scale of their adaptation. Climate is often considered the major driver of local adaptation but, although biotic factors such as soil pathogens or mutualists could be as important, their role has typically been neglected. Biotic drivers might also interact with climate to affect performance and mycorrhizae, in particular, are likely to play a key role in determining drought resistance, which is important in the context of adaptation to future environmental change. To address these questions, we performed a fully reciprocal soil-plant transplant experiment using Fagus sylvatica seedlings and soils from three regions in Germany. To separate the biotic and abiotic effects of inoculation, half of the plants were inoculated with natural soil from the different origins, while the rest were grown on sterilized substrate. We also imposed a drought stress treatment to test for interactions between soil biota and climate. After 1 year of growth, we measured aboveground biomass of all seedlings, and quantified mycorrhizal colonization for a subset of the seedlings, which included all soil-plant combinations, to disentangle the effect of mycorrhiza from other agents.

RESULTS: We found that plant origin had the strongest effect on plant performance, but this interacted with soil origin. In general, trees showed a slight tendency to produce less aboveground biomass on local soils, suggesting soil antagonists could be causing trees to be maladapted to their local soils. Consistently, we found lower mycorrhizal colonization rate under local soil conditions. Across all soils, seedlings from low elevations produced more annual biomass than middle (+ 290%) and high (+ 97%) elevations. Interestingly, mycorrhizal colonization increased with drought in the two provenances that showed higher drought tolerance, which supports previous results showing that mycorrhizae can increase drought resistance.

CONCLUSIONS: Our findings suggest that soil communities play a role in affecting early performance of temperate trees, although this role may be smaller than that of seed origin. Also, other effects, such as the positive response to generalists or negative interactions with soil biota may be as important as the highly specialized mycorrhizal associations.}, } @article {pmid30285726, year = {2018}, author = {Cook, D and Achanta, S and Hoek, JB and Ogunnaike, BA and Vadigepalli, R}, title = {Cellular network modeling and single cell gene expression analysis reveals novel hepatic stellate cell phenotypes controlling liver regeneration dynamics.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {86}, pmid = {30285726}, issn = {1752-0509}, support = {T32 AA007463//National Institute on Alcohol Abuse and Alcoholism/ ; U01 EB023224//National Institute of Biomedical Imaging and Bioengineering/ ; R01 AA018873/AA/NIAAA NIH HHS/United States ; R01 AA018873//National Institute on Alcohol Abuse and Alcoholism/ ; F31 AA023445/AA/NIAAA NIH HHS/United States ; F31 AA023445//National Institute on Alcohol Abuse and Alcoholism/ ; EAGER 1747917//National Science Foundation/ ; T32 AA007463/AA/NIAAA NIH HHS/United States ; }, abstract = {BACKGROUND: Recent results from single cell gene and protein regulation studies are starting to uncover the previously underappreciated fact that individual cells within a population exhibit high variability in the expression of mRNA and proteins (i.e., molecular variability). By combining cellular network modeling, and high-throughput gene expression measurements in single cells, we seek to reconcile the high molecular variability in single cells with the relatively low variability in tissue-scale gene and protein expression and the highly coordinated functional responses of tissues to physiological challenges. In this study, we focus on relating the dynamic changes in distributions of hepatic stellate cell (HSC) functional phenotypes to the tightly regulated physiological response of liver regeneration.

RESULTS: We develop a mathematical model describing contributions of HSC functional phenotype populations to liver regeneration and test model predictions through isolation and transcriptional characterization of single HSCs. We identify and characterize four HSC transcriptional states contributing to liver regeneration, two of which are described for the first time in this work. We show that HSC state populations change in vivo in response to acute challenges (in this case, 70% partial hepatectomy) and chronic challenges (chronic ethanol consumption). Our results indicate that HSCs influence the dynamics of liver regeneration through steady-state tissue preconditioning prior to an acute insult and through dynamic control of cell state balances. Furthermore, our modeling approach provides a framework to understand how balances among cell states influence tissue dynamics.

CONCLUSIONS: Taken together, our combined modeling and experimental studies reveal novel HSC transcriptional states and indicate that baseline differences in HSC phenotypes as well as a dynamic balance of transitions between these phenotypes control liver regeneration responses.}, } @article {pmid30285717, year = {2018}, author = {Kvasnes, MAJ and Pedersen, HC and Nilsen, EB}, title = {Quantifying suitable late summer brood habitats for willow ptarmigan in Norway.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {41}, pmid = {30285717}, issn = {1472-6785}, abstract = {BACKGROUND: Habitat models provide information about which habitat management should target to avoid species extinctions or range contractions. The willow ptarmigan inhabits alpine- and arctic tundra habitats in the northern hemisphere and is listed as near threatened (NT) in the Norwegian red list due to declining population size. Habitat alteration is one of several factors affecting willow ptarmigan populations, but there is a lack of studies quantifying and describing habitat selection in willow ptarmigan. We used data from an extensive line transect survey program from 2014 to 2017 to develop resource selection functions (RSF) for willow ptarmigan in Norway. The selection coefficients for the RSF were estimated using a mixed-effects logistic regression model fitted with random intercepts for each area. We predicted relative probability of selection across Norway and quantile-binned the predictions in 10 RSF bins ranging from low-(1) to high-(10) relative probability of selection.

RESULTS: Random cross-validation suggest that our models were highly predictive, but validation based spatial blocking revealed that the predictability was better in southern parts of Norway compared to the northernmost region. Willow ptarmigan selected for herb-rich meadows and avoided lichen rich heathlands. There was generally stronger selection for vegetation types with dense field layer and for rich bogs and avoidance of vegetation types with sparse field layer cover and for lowland forest. Further, willow ptarmigan selected for areas around the timberline and for intermediate slopes. Mapping of the RSF showed that 60% of Norway is in the lowest ranked RSF bin and only 2% in the highest ranked RSF bin.

CONCLUSIONS: Willow ptarmigan selected for vegetation types with dense field layer and bogs at intermediate slopes around the timberline. Selection coincides with previous habitat selection studies on willow ptarmigan. This is the first attempt to assess and quantify habitat selection for willow ptarmigan at a large scale using data from line transect distance sampling surveys. Spatial variation in predictability suggests that habitat selection in late summer might vary from north to south. The resource selection map can be a useful tool when planning harvest quotas and habitat interventions in alpine areas.}, } @article {pmid30285707, year = {2018}, author = {Kamgang, SA and Bobo, KS and Maisels, F and Ambahe, RDD and Ambassa Ongono, DE and Gonder, MK and Johnson, P and Marino, J and Sinsin, B}, title = {The relationship between the abundance of the Nigeria-Cameroon chimpanzee (Pan troglodytes ellioti) and its habitat: a conservation concern in Mbam-Djerem National Park, Cameroon.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {40}, pmid = {30285707}, issn = {1472-6785}, support = {ST68//WWf Russel E.Train education Nature/International ; 13184_1//Rufford Foundation/International ; 20258_2//Rufford Foundation/International ; }, abstract = {BACKGROUND: Understanding the relationship between great apes and their habitat is essential for the development of successful conservation strategies. The chimpanzee Pan troglodytes ellioti is endemic to Nigeria and Cameroon, and occupies an ecologically diverse range of habitats from forests to forest-savannah mosaic in Mbam-Djerem National Park (MDNP) in Cameroon. The habitat variation in chimpanzees is poorly understood in MDNP which provides an excellent opportunity to assess ecological factors that shape the abundance and distribution patterns of P. t. ellioti over a small geographic scale.

RESULTS: We counted 249 nests along 132 km of transects in total. Of these, 119 nests along 68 km occurred in dense forest and 130 nests along 64 km in forest-savannah mosaic. Chimpanzee density was 0.88 [95% CI (0.55-1.41)] individuals/km2 in the dense forest and 0.59 [95% CI (0.19-1.76)] in the forest-savannah mosaic. Nest abundance varied with vegetation type and was higher in areas with dense canopy cover, steeper slopes and relatively higher altitudes.

CONCLUSIONS: Our estimates of chimpanzee densities were lower than reported in other studied populations in the range of the Nigeria-Cameroon chimpanzee. However, we found that habitat features, slope and altitude likely play a role in shaping patterns of chimpanzee nesting ecology. Further studies need to be focused on nest decay rates and phenology of useful plants in order to model chimpanzee abundance and distribution in Mbam-Djerem National Park.}, } @article {pmid30285698, year = {2018}, author = {Albaladejo, I and Egea, I and Morales, B and Flores, FB and Capel, C and Lozano, R and Bolarin, MC}, title = {Identification of key genes involved in the phenotypic alterations of res (restored cell structure by salinity) tomato mutant and its recovery induced by salt stress through transcriptomic analysis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {213}, pmid = {30285698}, issn = {1471-2229}, support = {AGL2015-64991-C3-2-R//Ministerio de Economía y Competitividad/ ; AGL2015-64991-C3-1-R//Ministerio de Economía y Competitividad/ ; Code TC0000100 from CSIC Open Access Publication Support Initiative, Unit of Information Resources for Research (URICI)//Consejo Superior de Investigaciones Científicas/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; Lycopersicon esculentum/cytology/drug effects/*physiology ; Mutation ; Phenotype ; Photosynthesis/genetics ; Plant Cells/physiology/ultrastructure ; Plant Growth Regulators/genetics/metabolism ; Plant Proteins/*genetics/metabolism ; Reproducibility of Results ; Salinity ; Salt Tolerance/*genetics/physiology ; Signal Transduction/genetics ; Sodium Chloride/pharmacology ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: The res (restored cell structure by salinity) mutant, recently identified as the first tomato mutant accumulating jasmonate in roots under non-stressful conditions, exhibits a remarkable growth inhibition and morphological alterations in roots and leaves, which are suppressed when the mutant plants are exposed to salinity. In order to understand the molecular basis of the phenotype recovery induced by salt stress in the res mutant, we carried out a comparative transcriptomic analysis in roots and leaves of wild-type and res plants in absence of stress (control) and when the phenotypic recovery of res mutant began to be observed upon salt stress (5 days of 200 mM NaCl).

RESULTS: The number of differentially expressed genes was three times greater in roots than in leaves of res vs WT plants grown in control, and included the down-regulation of growth-promoting genes and the up-regulation of genes involved in Ca2+ signalling, transcription factors and others related to stress responses. However, these expression differences were attenuated under salt stress, coinciding with the phenotypic normalisation of the mutant. Contrarily to the attenuated response observed in roots, an enhanced response was found in leaves under salt stress. This included drastic expression changes in several circadian clock genes, such as GIGANTEA1, which was down-regulated in res vs WT plants. Moreover, the higher photosynthetic efficiency of res leaves under salt stress was accompanied by specific salt-upregulation of the genes RUBISCO ACTIVASE1 and ALTERNATIVE OXIDASE1A. Very few genes were found to be differentially expressed in both tissues (root and leaf) and conditions (control and salt), but this group included SlWRKY39 and SlMYB14 transcription factors, as well as genes related to protein homeostasis, especially protease inhibitors such as METALLOCARBOXYPEPTIDASE INHIBITOR, which also seem to play a role in the phenotype recovery and salt tolerance of res mutant.

CONCLUSIONS: In summary, in this study we have identified genes which seem to have a prominent role in salt tolerance. Moreover, we think this work could contribute to future breeding of tomato crops with increased stress tolerance.}, } @article {pmid30285631, year = {2018}, author = {Oney-Birol, S and Fitz-Gibbon, S and Chen, JM and Gugger, PF and Sork, VL}, title = {Assessment of shared alleles in drought-associated candidate genes among southern California white oak species (Quercus sect. Quercus).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {88}, pmid = {30285631}, issn = {1471-2156}, abstract = {BACKGROUND: Hybridization and introgression are common phenomena among oak species. These processes can be beneficial by introducing favorable genetic variants across species (adaptive introgression). Given that drought is an important stress, impacting physiological and morphological variation and limiting distributions, our goal was to identify drought-related genes that might exhibit patterns of introgression influenced by natural selection. Using RNAseq, we sequenced whole transcriptomes of 24 individuals from three oaks in southern California: (Quercus engelmannii, Quercus berberidifolia, Quercus cornelius-mulleri) and identified genetic variants to estimate admixture rates of all variants and those in drought genes.

RESULTS: We found 398,042 variants across all loci and 4352 variants in 139 drought candidate genes. STRUCTURE analysis of all variants revealed the majority of our samples were assignable to a single species, but with several highly admixed individuals. When using drought-associated variants, the same individuals exhibited less admixture and their allele frequencies were more polarized between Engelmann and scrub oaks than when using the total gene set. These findings are consistent with the hypothesis that selection may act differently on functional genes, such as drought-associated genes, and point to candidate genes that are suggestive of divergent selection among species maintaining adaptive differences. For example, the drought genes that showed the strongest bias against engelmannii-fixed oak variants in scrub oaks were related to sugar transporter, coumarate-coA ligases, glutathione S-conjugation, and stress response.

CONCLUSION: This pilot study illustrates that whole transcriptomes of individuals will provide useful data for identifying functional genes that contribute to adaptive divergence among hybridizing species.}, } @article {pmid30285630, year = {2018}, author = {Kunzmann, P and Hamacher, K}, title = {Biotite: a unifying open source computational biology framework in Python.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {346}, pmid = {30285630}, issn = {1471-2105}, mesh = {*Aluminum Silicates ; Computational Biology/*methods ; *Ferrous Compounds ; Programming Languages ; Software ; }, abstract = {BACKGROUND: As molecular biology is creating an increasing amount of sequence and structure data, the multitude of software to analyze this data is also rising. Most of the programs are made for a specific task, hence the user often needs to combine multiple programs in order to reach a goal. This can make the data processing unhandy, inflexible and even inefficient due to an overhead of read/write operations. Therefore, it is crucial to have a comprehensive, accessible and efficient computational biology framework in a scripting language to overcome these limitations.

RESULTS: We have developed the Python package Biotite: a general computational biology framework, that represents sequence and structure data based on NumPyndarrays. Furthermore the package contains seamless interfaces to biological databases and external software. The source code is freely accessible at https://github.com/biotite-dev/biotite .

CONCLUSIONS: Biotite is unifying in two ways: At first it bundles popular tasks in sequence analysis and structural bioinformatics in a consistently structured package. Secondly it adresses two groups of users: novice programmers get an easy access to Biotite due to its simplicity and the comprehensive documentation. On the other hand, advanced users can profit from its high performance and extensibility. They can implement their algorithms upon Biotite, so they can skip writing code for general functionality (like file parsers) and can focus on what their software makes unique.}, } @article {pmid30285628, year = {2018}, author = {Ellison, AR and Uren Webster, TM and Rey, O and Garcia de Leaniz, C and Consuegra, S and Orozco-terWengel, P and Cable, J}, title = {Transcriptomic response to parasite infection in Nile tilapia (Oreochromis niloticus) depends on rearing density.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {723}, pmid = {30285628}, issn = {1471-2164}, support = {AquaWales//NRN-LCEE/ ; }, mesh = {Animals ; Cichlids/*genetics/growth & development/*parasitology ; *Gene Expression Profiling ; Gills/metabolism/parasitology ; Saprolegnia/*physiology ; Skin/metabolism/parasitology ; Survival Analysis ; }, abstract = {BACKGROUND: Captive animal populations, be it for food production or conservation programmes, are often maintained at densities far beyond those in natural environments, which can have profound effects on behaviour, immune and stress levels, and ultimately welfare. How such alterations impact transcriptional responses to pathogen infection is a 'different kettle of fish' and remains poorly understood. Here, we assessed survival and gene expression profiles of infected fish reared at two different densities to elucidate potential functional genomic mechanisms for density-related differences in disease susceptibility.

RESULTS: Utilising a whole-transcriptome sequencing (RNAseq) approach, we demonstrate that rearing density in tilapia (Oreochromis niloticus) significantly impacts susceptibility to the oomycete Saprolegnia parasitica, via altered transcriptional infection responses. Tilapia held at low densities have increased expression of genes related to stress, likely due to increased aggressive interactions. When challenged with Saprolegnia, low-density fish exhibit altered expression of inflammatory gene responses and enhanced levels of adaptive immune gene suppression compared to fish reared at higher density, resulting in significantly increased mortality rates. In addition, Saprolegnia infection substantially perturbs expression of circadian clock genes, with fish reared at low-density having higher levels of molecular clock dysregulation.

CONCLUSIONS: Our results reveal the wide-scale impact of stocking density on transcriptional responses to infection and highlight the need to incorporate circadian biology into our understanding of disease dynamics in managed animals.}, } @article {pmid30285626, year = {2018}, author = {Hernández-González, IL and Moreno-Hagelsieb, G and Olmedo-Álvarez, G}, title = {Environmentally-driven gene content convergence and the Bacillus phylogeny.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {148}, pmid = {30285626}, issn = {1471-2148}, support = {//CIHR/Canada ; }, mesh = {Bacillus/*classification/*genetics ; Cluster Analysis ; *Environment ; Evolution, Molecular ; *Genes, Bacterial ; Genomics ; Phylogeny ; }, abstract = {BACKGROUND: Members of the Bacillus genus have been isolated from a variety of environments. However, the relationship between potential metabolism and the niche from which bacteria of this genus have been isolated has not been extensively studied. The existence of a monophyletic aquatic Bacillus group, composed of members isolated from both marine and fresh water has been proposed. Here, we present a phylogenetic/phylogenomic analysis to investigate the potential relationship between the environment from which group members have been isolated and their evolutionary origin. We also carried out hierarchical clustering based on functional content to test for potential environmental effects on the genetic content of these bacteria.

RESULTS: The phylogenetic reconstruction showed that Bacillus strains classified as aquatic have evolutionary origins in different lineages. Although we observed the presence of a clade consisting exclusively of aquatic Bacillus, it is not comprised of the same strains previously reported. In contrast to phylogeny, clustering based on the functional categories of the encoded proteomes resulted in groups more compatible with the environments from which the organisms were isolated. This evidence suggests a detectable environmental influence on bacterial genetic content, despite their different evolutionary origins.

CONCLUSION: Our results suggest that aquatic Bacillus species have polyphyletic origins, but exhibit convergence at the gene content level.}, } @article {pmid30285625, year = {2018}, author = {Pacchioni, F and Esposito, A and Giacobazzi, E and Bettua, C and Struffi, P and Jousson, O}, title = {Air and waterborne microbiome of a pharmaceutical plant provide insights on spatiotemporal variations and community resilience after disturbance.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {124}, pmid = {30285625}, issn = {1471-2180}, abstract = {BACKGROUND: The presence of microrganisms in pharmaceutical production plant environments is typically monitored by cultural methods, however these cannot detect the unculturable fraction of the microbial community. To get more accurate information on the composition of these indoor microbial communities, both water and air microbiome from a pharmaceutical production plant were profiled by 16S amplicon sequencing.

RESULTS: In the water system, we found taxa which typically characterize surface freshwater, groundwater and oligotrophic environments. The airborne microbiome resulted dominated by taxa usually found in outdoor air in combination with human-associated taxa. The alpha- and beta- diversity values showed that the heat-based sanitization process of the water plant affects the composition of the water microbiome by transiently increasing both diversity and evenness. Taxonomic compositional shifts were also detected in response to sanitization, consisting in an increase of Firmicutes and α-Proteobacteria. On the other hand, seasonality seems to be the main driver of bacterial community composition in air of this work environment.

CONCLUSIONS: This approach resulted useful to describe the taxonomy of these indoor microbiomes and could be further applied to other built environments, in which the knowledge of the microbiome composition is of relevance. In addition, this study could assist in the design of new guidelines to improve microbiological quality control in indoor work environments.}, } @article {pmid30285624, year = {2018}, author = {Howells, RM and Craze, M and Bowden, S and Wallington, EJ}, title = {Efficient generation of stable, heritable gene edits in wheat using CRISPR/Cas9.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {215}, pmid = {30285624}, issn = {1471-2229}, support = {BB/J019356/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Agrobacterium/genetics ; *CRISPR-Cas Systems ; DNA, Bacterial ; Gene Editing/*methods ; Genome, Plant ; Hordeum/genetics ; Plant Breeding/methods ; Plants, Genetically Modified/genetics ; Transformation, Genetic ; Triticum/*genetics ; }, abstract = {BACKGROUND: The use of CRISPR/Cas9 systems could prove to be a valuable tool in crop research, providing the ability to fully knockout gene function in complex genomes or to precisely adjust gene function by knockout of individual alleles.

RESULTS: We compare gene editing in hexaploid wheat (Triticum aestivum) with diploid barley (Hordeum vulgare), using a combination of single genome and tri-genome targeting. High efficiency gene editing, 11-17% for single genome targeted guides and 5% for tri-genome targeted guides, was achieved in wheat using stable Agrobacterium-mediated transformation. Gene editing in wheat was shown to be predominantly heterozygous, edits were inherited in a Mendelian fashion over multiple generations and no off-target effects were observed. Comparison of editing between the two species demonstrated that more stable, heritable edits were produced in wheat, whilst barley exhibited continued and somatic editing.

CONCLUSION: Our work shows the potential to obtain stable edited transgene-free wheat lines in 36 weeks through only two generations and that targeted mutagenesis of individual homeologues within the wheat genome is achievable with a modest amount of effort, and without off-target mutations or the need for lengthy crossing strategies.}, } @article {pmid30285622, year = {2018}, author = {Nitarska, D and Stefanini, C and Haselmair-Gosch, C and Miosic, S and Walliser, B and Mikulic-Petkovsek, M and Regos, I and Slatnar, A and Debener, T and Terefe-Ayana, D and Vilperte, V and Hadersdorfer, J and Stich, K and Halbwirth, H}, title = {The rare orange-red colored Euphorbia pulcherrima cultivar 'Harvest Orange' shows a nonsense mutation in a flavonoid 3'-hydroxylase allele expressed in the bracts.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {216}, pmid = {30285622}, issn = {1471-2229}, support = {675657 - FLOWERPOWER - H2020-MSCA-ITN-2015/H2020-MSCA-ITN-2015//H2020 Marie Skłodowska-Curie Actions/ ; P 28134-B25//FWF/ ; P4-0013-0481//Javna Agencija za Raziskovalno Dejavnost RS/ ; }, mesh = {Alcohol Oxidoreductases/genetics ; Anthocyanins/genetics/metabolism ; Cloning, Molecular ; *Codon, Nonsense ; Cytochrome P-450 Enzyme System/*genetics ; Euphorbia/*genetics/metabolism ; Gene Expression Regulation, Plant ; Pigmentation/genetics ; Plant Proteins/*genetics ; Real-Time Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Commercially available poinsettia (Euphorbia pulcherrima) varieties prevalently accumulate cyanidin derivatives and show intense red coloration. Orange-red bract color is less common. We investigated four cultivars displaying four different red hues with respect to selected enzymes and genes of the anthocyanin pathway, putatively determining the color hue.

RESULTS: Red hues correlated with anthocyanin composition and concentration and showed common dark red coloration in cultivars 'Christmas Beauty' and 'Christmas Feeling' where cyanidin derivatives were prevalent. In contrast, orange-red bract color is based on the prevalent presence of pelargonidin derivatives that comprised 85% of the total anthocyanin content in cv. 'Premium Red' and 96% in cv. 'Harvest Orange' (synonym: 'Orange Spice'). cDNA clones of flavonoid 3'-hydroxylase (F3'H) and dihydroflavonol 4-reductase (DFR) were isolated from the four varieties, and functional activity and substrate specificity of the corresponding recombinant enzymes were studied. Kinetic studies demonstrated that poinsettia DFRs prefer dihydromyricetin and dihydroquercetin over dihydrokaempferol, and thus, favor the formation of cyanidin over pelargonidin. Whereas the F3'H cDNA clones of cultivars 'Christmas Beauty', 'Christmas Feeling', and 'Premium Red' encoded functionally active enzymes, the F3'H cDNA clone of cv. 'Harvest Orange' contained an insertion of 28 bases, which is partly a duplication of 20 bases found close to the insertion site. This causes a frameshift mutation with a premature stop codon after nucleotide 132 and, therefore, a non-functional enzyme. Heterozygosity of the F3'H was demonstrated in this cultivar, but only the mutated allele was expressed in the bracts. No correlation between F3'H-expression and the color hue could be observed in the four species.

CONCLUSIONS: Rare orange-red poinsettia hues caused by pelargonidin based anthocyanins can be achieved by different mechanisms. F3'H is a critical step in the establishment of orange red poinsettia color. Although poinsettia DFR shows a low substrate specificity for dihydrokaempferol, sufficient precursor for pelargonidin formation is available in planta, in the absence of F3'H activity.}, } @article {pmid30285621, year = {2018}, author = {Bruinsma, S and Burgess, J and Schlingman, D and Czyz, A and Morrell, N and Ballenger, C and Meinholz, H and Brady, L and Khanna, A and Freeberg, L and Jackson, RG and Mathonet, P and Verity, SC and Slatter, AF and Golshani, R and Grunenwald, H and Schroth, GP and Gormley, NA}, title = {Bead-linked transposomes enable a normalization-free workflow for NGS library preparation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {722}, pmid = {30285621}, issn = {1471-2164}, mesh = {DNA Transposable Elements/*genetics ; *Gene Library ; Genome, Human/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Magnets/chemistry ; *Microspheres ; Plasmids/genetics ; *Workflow ; }, abstract = {BACKGROUND: Transposome-based technologies have enabled the streamlined production of sequencer-ready DNA libraries; however, current methods are highly sensitive to the amount and quality of input nucleic acid.

RESULTS: We describe a new library preparation technology (Nextera DNA Flex) that utilizes a known concentration of transposomes conjugated directly to beads to bind a fixed amount of DNA, and enables direct input of blood and saliva using an integrated extraction protocol. We further report results from libraries generated outside the standard parameters of the workflow, highlighting novel applications for Nextera DNA Flex, including human genome builds and variant calling from below 1 ng DNA input, customization of insert size, and preparation of libraries from short fragments and severely degraded FFPE samples. Using this bead-linked library preparation method, library yield saturation was observed at an input amount of 100 ng. Preparation of libraries from a range of species with varying GC levels demonstrated uniform coverage of small genomes. For large and complex genomes, coverage across the genome, including difficult regions, was improved compared with other library preparation methods. Libraries were successfully generated from amplicons of varying sizes (from 50 bp to 11 kb), however, a decrease in efficiency was observed for amplicons smaller than 250 bp. This library preparation method was also compatible with poor-quality DNA samples, with sequenceable libraries prepared from formalin-fixed paraffin-embedded samples with varying levels of degradation.

CONCLUSIONS: In contrast to solution-based library preparation, this bead-based technology produces a normalized, sequencing-ready library for a wide range of DNA input types and amounts, largely obviating the need for DNA quantitation. The robustness of this bead-based library preparation kit and flexibility of input DNA facilitates application across a wide range of fields.}, } @article {pmid30285620, year = {2018}, author = {Wright, ES and Baum, DA}, title = {Exclusivity offers a sound yet practical species criterion for bacteria despite abundant gene flow.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {724}, pmid = {30285620}, issn = {1471-2164}, mesh = {*Gene Flow ; Gene Transfer, Horizontal ; Genes, Bacterial/genetics ; Phylogeny ; Streptomycetaceae/*classification/*genetics ; }, abstract = {BACKGROUND: The question of whether bacterial species objectively exist has long divided microbiologists. A major source of contention stems from the fact that bacteria regularly engage in horizontal gene transfer (HGT), making it difficult to ascertain relatedness and draw boundaries between taxa. A natural way to define taxa is based on exclusivity of relatedness, which applies when members of a taxon are more closely related to each other than they are to any outsider. It is largely unknown whether exclusive bacterial taxa exist when averaging over the genome or are rare due to rampant hybridization.

RESULTS: Here, we analyze a collection of 701 genomes representing a wide variety of environmental isolates from the family Streptomycetaceae, whose members are competent at HGT. We find that the presence/absence of auxiliary genes in the pan-genome displays a hierarchical (tree-like) structure that correlates significantly with the genealogy of the core-genome. Moreover, we identified the existence of many exclusive taxa, although individual genes often contradict these taxa. These conclusions were supported by repeating the analysis on 1,586 genomes belonging to the genus Bacillus. However, despite confirming the existence of exclusive groups (taxa), we were unable to identify an objective threshold at which to assign the rank of species.

CONCLUSIONS: The existence of bacterial taxa is justified by considering average relatedness across the entire genome, as captured by exclusivity, but is rejected if one requires unanimous agreement of all parts of the genome. We propose using exclusivity to delimit taxa and conventional genome similarity thresholds to assign bacterial taxa to the species rank. This approach recognizes species that are phylogenetically meaningful, while also establishing some degree of comparability across species-ranked taxa in different bacterial clades.}, } @article {pmid30285619, year = {2018}, author = {Feng, G and Xu, L and Wang, J and Nie, G and Bushman, BS and Xie, W and Yan, H and Yang, Z and Guan, H and Huang, L and Zhang, X}, title = {Integration of small RNAs and transcriptome sequencing uncovers a complex regulatory network during vernalization and heading stages of orchardgrass (Dactylis glomerata L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {727}, pmid = {30285619}, issn = {1471-2164}, support = {No.2014CB138705//National Basic Research Program (973 program) in China/ ; No. CARS-34//the earmarked fund for Modern Agro-industry Technology Research System/ ; NSFC 31872997//the National Natural Science Foundation of China/ ; }, mesh = {Dactylis/*genetics/*growth & development ; Flowers/*growth & development ; *Gene Expression Profiling ; *Gene Regulatory Networks ; MicroRNAs/*genetics ; Molecular Sequence Annotation ; }, abstract = {BACKGROUND: Flowering is a critical reproductive process in higher plants. Timing of optimal flowering depends upon the coordination among seasonal environmental cues. For cool season grasses, such as Dactylis glomerata, vernalization induced by low temperature provides competence to initiate flowering after prolonged cold. We combined analyses of the transcriptome and microRNAs (miRNAs) to generate a comprehensive resource for regulatory miRNAs and their target circuits during vernalization and heading stages.

RESULTS: A total of 3,846 differentially expressed genes (DEGs) and 69 differentially expressed miRNAs were identified across five flowering stages. The expression of miR395, miR530, miR167, miR396, miR528, novel_42, novel_72, novel_107, and novel_123 demonstrated significant variations during vernalization. These miRNA targeted genes were involved in phytohormones, transmembrane transport, and plant morphogenesis in response to vernalization. The expression patterns of DEGs related to plant hormones, stress responses, energy metabolism, and signal transduction changed significantly in the transition from vegetative to reproductive phases.

CONCLUSIONS: Five hub genes, c136110_g1 (BRI1), c131375_g1 (BZR1), c133350_g1 (VRN1), c139830_g1 (VIN3), and c125792_g2 (FT), might play central roles in vernalization response. Our comprehensive analyses have provided a useful platform for investigating consecutive transcriptional and post-transcriptional regulation of critical phases in D. glomerata and provided insights into the genetic engineering of flowering-control in cereal crops.}, } @article {pmid30285618, year = {2018}, author = {Tsikou, D and Ramirez, EE and Psarrakou, IS and Wong, JE and Jensen, DB and Isono, E and Radutoiu, S and Papadopoulou, KK}, title = {A Lotus japonicus E3 ligase interacts with the Nod Factor Receptor 5 and positively regulates nodulation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {217}, pmid = {30285618}, issn = {1471-2229}, support = {3817//Department of Biochemistry and Biotechnology/ ; 290713-031130//European Cooperation in Science and Technology/ ; DNRF79//Danmarks Grundforskningsfond/ ; }, mesh = {Gene Expression Regulation, Plant ; Lotus/*physiology ; Mesorhizobium/physiology ; Mutation ; Plant Proteins/genetics/*metabolism ; Plant Root Nodulation/*physiology ; Plants, Genetically Modified ; Protein-Serine-Threonine Kinases/metabolism ; Root Nodules, Plant/genetics/microbiology ; Symbiosis ; Ubiquitin-Protein Ligases/genetics/metabolism ; Ubiquitination ; }, abstract = {BACKGROUND: Post-translational modification of receptor proteins is involved in activation and de-activation of signalling systems in plants. Both ubiquitination and deubiquitination have been implicated in plant interactions with pathogens and symbionts.

RESULTS: Here we present LjPUB13, a PUB-ARMADILLO repeat E3 ligase that specifically ubiquitinates the kinase domain of the Nod Factor receptor NFR5 and has a direct role in nodule organogenesis events in Lotus japonicus. Phenotypic analyses of three LORE1 retroelement insertion plant lines revealed that pub13 plants display delayed and reduced nodulation capacity and retarded growth. LjPUB13 expression is spatially regulated during symbiosis with Mesorhizobium loti, with increased levels in young developing nodules.

CONCLUSION: LjPUB13 is an E3 ligase with a positive regulatory role during the initial stages of nodulation in L. japonicus.}, } @article {pmid30285617, year = {2018}, author = {Liley, J}, title = {Combining controls can improve power in two-stage association studies.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {89}, pmid = {30285617}, issn = {1471-2156}, support = {//Wellcome Trust/United Kingdom ; 107881//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: High dimensional case control studies are ubiquitous in the biological sciences, particularly genomics. To maximise power while constraining cost and to minimise type-1 error rates, researchers typically seek to replicate findings in a second experiment on independent cohorts before proceeding with further analyses. This can be an expensive procedure, particularly when control samples are difficult to recruit or ascertain; for example in inter-disease comparisons, or studies on degenerative diseases.

RESULTS: This paper presents a method in which control (or case) samples from the discovery cohort are re-used in a replication study. The theoretical implications of this method are discussed and simulated genome-wide association study (GWAS) tests are used to compare performance against the standard approach in a range of circumstances. Using similar methods, a procedure is proposed for 'partial replication' using a new independent cohort consisting of only controls. This methods can be used to provide some validation of findings when a full replication procedure is not possible. The new method has differing sensitivity to confounding in study cohorts compared to the standard procedure, which must be considered in its application. Type-1 error rates in these scenarios are analytically and empirically derived, and an online tool for comparing power and error rates is provided.

CONCLUSIONS: In several common study designs, a shared-control method allows a substantial improvement in power while retaining type-1 error rate control. Although careful consideration must be made of all necessary assumptions, this method can enable more efficient use of data in GWAS and other applications.}, } @article {pmid30285616, year = {2018}, author = {Dong, Y and Zhao, Q and Liu, X and Zhang, X and Qi, Z and Zhang, H and Zheng, X and Zhang, Z}, title = {Correction to: MoMyb1 is required for asexual development and tissue-specific infection in the rice blast fungus Magnaporthe oryzae.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {123}, pmid = {30285616}, issn = {1471-2180}, abstract = {Following the publication of this article [1], the authors noticed that they mistakenly introduced duplicate images in Figure 6A during the preparation of figures. They apologize for any confusion that brought to the readers and have corrected the figure. This correction does not change any statement or conclusion drawn from the data.}, } @article {pmid30285615, year = {2018}, author = {Zhao, YJ and Cao, Y and Wang, J and Xiong, Z}, title = {Transcriptome sequencing of Pinus kesiya var. langbianensis and comparative analysis in the Pinus phylogeny.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {725}, pmid = {30285615}, issn = {1471-2164}, support = {2015Y287//Project of Education Department of Yunnan Province/ ; 31660029//National Natural Science Foundation/ ; }, mesh = {Environment ; Evolution, Molecular ; *Gene Expression Profiling ; Geography ; Microsatellite Repeats/genetics ; *Phylogeny ; Pinus/*genetics ; Polymorphism, Single Nucleotide ; *Sequence Analysis ; Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: Pines are widely distributed in the Northern Hemisphere and have a long evolutionary history. The availability of transcriptome data has facilitated comparative transcriptomics for studying the evolutionary patterns associated with the different geographical distributions of species in the Pinus phylogeny.

RESULTS: The transcriptome of Pinus kesiya var. langbianensis was sequenced using the Illumina HiSeq 2000 platform, and a total of 68,881 unigenes were assembled by Trinity. Transcriptome sequences of another 12 conifer species were downloaded from public databases. All of the pairwise orthologues were identified by comparative transcriptome analysis in 13 conifer species, from which the rate of diversification was calculated and a phylogenetic tree inferred. All of the fast-evolving positive selection sequences were identified, and some salt-, drought-, and abscisic acid-resistance genes were discovered.

CONCLUSIONS: mRNA sequences of P. kesiya var. langbianensis were obtained by transcriptome sequencing, and a large number of simple sequence repeat and short nucleotide polymorphism loci were detected. These data can be used in molecular marker-assisted selected in pine breeding. Divergence times were estimated in the 13 conifer species using comparative transcriptomic analysis. A number of positive selection genes were found to be related to environmental factors. Salt- and abscisic acid-related genes exhibited different selection patterns between coastal and inland Pinus. Our findings help elucidate speciation patterns in the Pinus lineage.}, } @article {pmid30285614, year = {2018}, author = {Ahmad, M and Yan, X and Li, J and Yang, Q and Jamil, W and Teng, Y and Bai, S}, title = {Genome wide identification and predicted functional analyses of NAC transcription factors in Asian pears.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {214}, pmid = {30285614}, issn = {1471-2229}, support = {31772272//National Natural Science Foundation of China/ ; 31501736//National Natural Science Foundation of China/ ; 31471852//National Natural Science Foundation of China/ ; CARS-28//Earmarked Fund for China Agriculture Research System/ ; }, mesh = {Amino Acid Motifs ; Fruit/genetics/growth & development ; Gene Duplication ; Gene Expression Regulation, Plant ; Genome, Plant ; Multigene Family ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Pyrus/*genetics/*growth & development ; Sequence Analysis, RNA ; Stress, Physiological/genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {BACKGROUND: NAC proteins contribute to diverse plant developmental processes as well as tolerances to biotic and abiotic stresses. The pear genome had been decoded and provided the basis for the genome-wide analysis to find the evolution, duplication, gene structures and predicted functions of PpNAC transcription factors.

RESULTS: A total of 185 PpNAC genes were found in pear, of which 148 were mapped on chromosomes while 37 were on unanchored scaffolds. Phylogeny split the NAC genes into 6 clades (Group1- Group6) with their sub clades (~ subgroup A to subgroup H) and each group displayed common motifs with no/minor change. The numbers of exons in each group varied from 1 to 12 with an average of 3 while 44 pairs from all groups showed their duplication events. qPCR and RNA-Seq data analyses in different pear cultivars/species revealed some predicted functions of PpNAC genes i.e. PpNACs 37, 61, 70 (2A), 53, 151(2D), 10, 92, 130 and 154 (3D) were potentially involved in bud endodormancy, PpNACs 61, 70 (2A), 172, 176 and 23 (4E) were associated with fruit pigmentations in blue light, PpNACs 127 (1E), 46 (1G) and 56 (5A) might be related to early, middle and late fruit developments respectively. Besides, all genes from subgroups 2D and 3D were found to be related with abiotic stress (cold, salt and drought) tolerances by targeting the stress responsive genes in pear.

CONCLUSIONS: The present genome-wide analysis provided valuable information for understanding the classification, motif and gene structure, evolution and predicted functions of NAC gene family in pear as well as in higher plants. NAC TFs play diverse and multifunctional roles in biotic and abiotic stresses, growth and development and fruit ripening and pigmentation through multiple pathways in pear.}, } @article {pmid30285613, year = {2018}, author = {Jørgensen, KM and Wennevik, V and Eide Sørvik, AG and Unneland, L and Prusov, S and Ayllon, F and Glover, KA}, title = {Investigating the frequency of triploid Atlantic salmon in wild Norwegian and Russian populations.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {90}, pmid = {30285613}, issn = {1471-2156}, support = {212529//FP7 Food, Agriculture and Fisheries, Biotechnology/ ; KO197//European Regional Development Fund/ ; }, abstract = {BACKGROUND: Fish may display variations in ploidy, including three sets of chromosomes, known as triploidy. A recent study revealed a frequency of ~ 2% spontaneous (i.e., non-intentional) triploidy in domesticated Atlantic salmon produced in Norwegian aquaculture in the period 2007-2014. In contrast, the frequency of triploidy in wild salmon populations has not been studied thus far, and in wild populations of other organisms, it has been very rarely studied. In population genetic data sets, individuals that potentially display chromosome abnormalities, such as triploids with three alleles, are typically excluded on the premise that they may reflect polluted or otherwise compromised samples. Here, we critically re-investigated the microsatellite genetic profile of ~ 6000 wild Atlantic salmon sampled from 80 rivers in Norway and Russia, to investigate the frequency of triploid individuals in wild salmon populations for the first time.

RESULTS: We detected a single triploid salmon, and five individuals displaying three alleles at one of the loci, thus regarded as putatively trisomic. This gave an overall frequency of triploid and putatively trisomic individuals in the data set of 0.017 and 0.083% respectively. The triploid salmon was an adult female, and had spent 2 years in freshwater and 2 years in the sea.

CONCLUSIONS: We conclude that the frequency of naturally-occurring triploid Atlantic salmon in wild Norwegian and Russian populations is very low, and many-fold lower than the frequency of spontaneous triploids observed in aquaculture. Our results suggest that aquaculture rearing conditions substantially increase the probability of triploidy to develop, and/or permits greater survival of triploid individuals, in comparison to the wild.}, } @article {pmid30285612, year = {2018}, author = {Sánchez-Rangel, D and Hernández-Domínguez, EE and Pérez-Torres, CA and Ortiz-Castro, R and Villafán, E and Rodríguez-Haas, B and Alonso-Sánchez, A and López-Buenfil, A and Carrillo-Ortiz, N and Hernández-Ramos, L and Ibarra-Laclette, E}, title = {Environmental pH modulates transcriptomic responses in the fungus Fusarium sp. associated with KSHB Euwallacea sp. near fornicatus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {721}, pmid = {30285612}, issn = {1471-2164}, support = {2016-1//Secretaría de Agricultura, Ganadería, Desarrollo Rural, Pesca y Alimentación (SAGARPA) - Servicio Nacional de Sanidad, Inocuidad y Calidad Agroalimentaria (SENASICA)/ ; 292399//Fondo Institucional de Fomento Regional para el Desarrollo Científico, Tecnológico y de Innovación (FORDECYT)/ ; }, mesh = {Animals ; *Environment ; Fusaric Acid/biosynthesis ; Fusarium/*genetics/growth & development/metabolism/*physiology ; *Gene Expression Profiling ; Hydrogen-Ion Concentration ; Molecular Sequence Annotation ; Phylogeny ; Sequence Homology, Nucleic Acid ; Symbiosis ; Weevils/*microbiology ; }, abstract = {BACKGROUND: The Ambrosia Fusarium Clade phytopathogenic Fusarium fungi species have a symbiotic relationship with ambrosia beetles in the genus Euwallacea (Coleoptera: Curculionidae). Related beetle species referred to as Euwallacea sp. near fornicatus have been spread in California, USA and are recognized as the causal agents of Fusarium dieback, a disease that causes mortality of many plant species. Despite the importance of this fungi, no transcriptomic resources have been generated. The datasets described here represent the first ever transcripts available for these species. We focused our study on the isolated species of Fusarium that is associated with one of the cryptic species referred to as Kuroshio Shot Hole Borer (KSHB) Euwallacea sp. near fornicatus.

RESULTS: Hydrogen concentration is a critical signal in fungi for growth and host colonization, the aim of this study was to evaluate the effect of different pH conditions on growth and gene expression of the fungus Fusarium sp. associated with KSHB. An RNA-seq approach was used to compare the gene expression of the fungus grown for 2 weeks in liquid medium at three different pH levels (5.0, 6.0, and 7.0). An unbuffered treatment was included to evaluate the capability of the fungus to change the pH of its environment and the impact in gene expression. The results showed that the fungus can grow and modulate its genetic expression at different pH conditions; however, growth was stunted in acidic pH in comparison with neutral pH. The results showed a differential expression pattern in each pH condition even when acidic conditions prevailed at the end of the experiment. After comparing transcriptomics data from the three treatments, we found a total of 4,943 unique transcripts that were differentially expressed.

CONCLUSIONS: We identified transcripts related to pH signaling such as the conserved PAL/RIM pathway, some transcripts related to secondary metabolism and other transcripts that were differentially expressed. Our analysis suggests possible mechanisms involved in pathogenicity in this novel Fusarium species. This is the first report that shows transcriptomic data of this pathogen as well as the first report of genes and proteins involved in their metabolism identifying potential virulence factors.}, } @article {pmid30285611, year = {2018}, author = {Gao, H and Wang, Z and Li, S and Hou, M and Zhou, Y and Zhao, Y and Li, G and Zhao, H and Ma, H}, title = {Genome-wide survey of potato MADS-box genes reveals that StMADS1 and StMADS13 are putative downstream targets of tuberigen StSP6A.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {726}, pmid = {30285611}, issn = {1471-2164}, support = {31500159//National Natural Science Foundation of China/ ; 2015JQ3090//Natural Science Foundation of Shaanxi Province/ ; }, mesh = {Amino Acid Motifs ; Conserved Sequence ; Evolution, Molecular ; Genome, Plant/genetics ; *Genomics ; MADS Domain Proteins/chemistry/genetics/*metabolism ; Organ Specificity ; Phylogeny ; Plant Proteins/*metabolism ; Plant Tubers/growth & development/metabolism ; Solanum tuberosum/*genetics/growth & development/*metabolism ; }, abstract = {BACKGROUND: MADS-box genes encode transcription factors that are known to be involved in several aspects of plant growth and development, especially in floral organ specification. To date, the comprehensive analysis of potato MADS-box gene family is still lacking after the completion of potato genome sequencing. A genome-wide characterization, classification, and expression analysis of MADS-box transcription factor gene family was performed in this study.

RESULTS: A total of 153 MADS-box genes were identified and categorized into MIKC subfamily (MIKCC and MIKC*) and M-type subfamily (Mα, Mβ, and Mγ) based on their phylogenetic relationships to the Arabidopsis and rice MADS-box genes. The potato M-type subfamily had 114 members, which is almost three times of the MIKC members (39), indicating that M-type MADS-box genes have a higher duplication rate and/or a lower loss rate during potato genome evolution. Potato MADS-box genes were present on all 12 potato chromosomes with substantial clustering that mainly contributed by the M-type members. Chromosomal localization of potato MADS-box genes revealed that MADS-box genes, mostly MIKC, were located on the duplicated segments of the potato genome whereas tandem duplications mainly contributed to the M-type gene expansion. The potato MIKC subfamily could be further classified into 11 subgroups and the TT16-like, AGL17-like, and FLC-like subgroups found in Arabidopsis were absent in potato. Moreover, the expressions of potato MADS-box genes in various tissues were analyzed by using RNA-seq data and verified by quantitative real-time PCR, revealing that the MIKCC genes were mainly expressed in flower organs and several of them were highly expressed in stolon and tubers. StMADS1 and StMADS13 were up-regulated in the StSP6A-overexpression plants and down-regulated in the StSP6A-RNAi plant, and their expression in leaves and/or young tubers were associated with high level expression of StSP6A.

CONCLUSION: Our study identifies the family members of potato MADS-box genes and investigate the evolution history and functional divergence of MADS-box gene family. Moreover, we analyze the MIKCC expression patterns and screen for genes involved in tuberization. Finally, the StMADS1 and StMADS13 are most likely to be downstream target of StSP6A and involved in tuber development.}, } @article {pmid30285610, year = {2018}, author = {Causey, DR and Pohl, MAN and Stead, DA and Martin, SAM and Secombes, CJ and Macqueen, DJ}, title = {High-throughput proteomic profiling of the fish liver following bacterial infection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {719}, pmid = {30285610}, issn = {1471-2164}, support = {BB/M026345///Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Aeromonas salmonicida/*physiology ; Animals ; Fish Proteins/*metabolism ; Gene Ontology ; Liver/immunology/*metabolism/*microbiology ; Oncorhynchus mykiss/genetics/immunology/*metabolism/*microbiology ; Protein Interaction Mapping ; *Proteomics ; }, abstract = {BACKGROUND: High-throughput proteomics was used to determine the role of the fish liver in defense responses to bacterial infection. This was done using a rainbow trout (Oncorhynchus mykiss) model following infection with Aeromonas salmonicida, the causative agent of furunculosis. The vertebrate liver has multifaceted functions in innate immunity, metabolism, and growth; we hypothesize this tissue serves a dual role in supporting host defense in parallel to metabolic adjustments that promote effective immune function. While past studies have reported mRNA responses to A. salmonicida in salmonids, the impact of bacterial infection on the liver proteome remains uncharacterized in fish.

RESULTS: Rainbow trout were injected with A. salmonicida or PBS (control) and liver extracted 48 h later for analysis on a hybrid quadrupole-Orbitrap mass spectrometer. A label-free method was used for protein abundance profiling, which revealed a strong innate immune response along with evidence to support parallel rewiring of metabolic and growth systems. 3076 proteins were initially identified against all proteins (n = 71,293 RefSeq proteins) annotated in a single high-quality rainbow trout reference genome, of which 2433 were maintained for analysis post-quality filtering. Among the 2433 proteins, 109 showed significant differential abundance following A. salmonicida challenge, including many upregulated complement system and acute phase response proteins, in addition to molecules with putative functions that may support metabolic re-adjustments. We also identified novel expansions in the complement system due to gene and whole genome duplication events in salmonid evolutionary history, including eight C3 proteins showing differential changes in abundance.

CONCLUSIONS: This study provides the first high-throughput proteomic examination of the fish liver in response to bacterial challenge, revealing novel markers for the host defense response, and evidence of metabolic remodeling in conjunction with activation of innate immunity.}, } @article {pmid30285608, year = {2018}, author = {Al-Kofahi, Y and Zaltsman, A and Graves, R and Marshall, W and Rusu, M}, title = {A deep learning-based algorithm for 2-D cell segmentation in microscopy images.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {365}, pmid = {30285608}, issn = {1471-2105}, mesh = {Algorithms ; Humans ; Microscopy/*methods ; }, abstract = {BACKGROUND: Automatic and reliable characterization of cells in cell cultures is key to several applications such as cancer research and drug discovery. Given the recent advances in light microscopy and the need for accurate and high-throughput analysis of cells, automated algorithms have been developed for segmenting and analyzing the cells in microscopy images. Nevertheless, accurate, generic and robust whole-cell segmentation is still a persisting need to precisely quantify its morphological properties, phenotypes and sub-cellular dynamics.

RESULTS: We present a single-channel whole cell segmentation algorithm. We use markers that stain the whole cell, but with less staining in the nucleus, and without using a separate nuclear stain. We show the utility of our approach in microscopy images of cell cultures in a wide variety of conditions. Our algorithm uses a deep learning approach to learn and predict locations of the cells and their nuclei, and combines that with thresholding and watershed-based segmentation. We trained and validated our approach using different sets of images, containing cells stained with various markers and imaged at different magnifications. Our approach achieved a 86% similarity to ground truth segmentation when identifying and separating cells.

CONCLUSIONS: The proposed algorithm is able to automatically segment cells from single channel images using a variety of markers and magnifications.}, } @article {pmid30285607, year = {2018}, author = {Kong, L and Zhao, K and Gao, Y and Miao, L and Chen, C and Deng, H and Liu, Z and Yu, X}, title = {Comparative analysis of cytokinin response factors in Brassica diploids and amphidiploids and insights into the evolution of Brassica species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {728}, pmid = {30285607}, issn = {1471-2164}, support = {2016YFD0100204-31//the National Key Research and Development Program of China/ ; 2014-Z28//the 948 Project of Agricultural Ministry of China/ ; 31460521//National Natural Science Foundation of China/ ; 31700272//National Natural Science Foundation of China/ ; 31872110//National Natural Science Foundation of China/ ; 2016C02051-6-1//the Breeding Project of the Sci-tech Foundation of Zhejiang Province/ ; 2015C110008//the Project of the Sci-tech Foundation of Ningbo City/ ; LGN18C150003//the Project of Application on Public Welfare Technology in Zhejiang Province/ ; CLE02N1603//the Development Project of Wuxi City/ ; }, mesh = {Brassica/drug effects/*genetics/growth & development/physiology ; Chromosomes, Plant/genetics ; *Diploidy ; *Evolution, Molecular ; Phylogeny ; Plant Proteins/*genetics ; Plant Roots/growth & development ; *Polyploidy ; Promoter Regions, Genetic/genetics ; Salts/pharmacology ; Selection, Genetic ; Stress, Physiological/drug effects/genetics ; Synteny ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: Cytokinin is a classical phytohormone that plays important roles in numerous plant growth and development processes. In plants, cytokinin signals are transduced by a two-component system, which involves many genes, including cytokinin response factors (CRFs). Although CRFs take vital part in the growth of Arabidopsis thaliana and Solanum lycopersicum, little information of the CRFs in the Brassica U-triangle species has been known yet.

RESULTS: We identified and compared 141 CRFs in the diploids and amphidiploids of Brassica species, including B. rapa, B. oleracea, B. nigra, B. napus, and B. juncea. For all the 141 CRFs, the sequence and structure analysis, physiological and biochemical characteristics analysis were performed. Meanwhile, the Ka/Ks ratios of orthologous and paralogous gene pairs were calculated, which indicated the natural selective pressure upon the overall length or a certain part of the CRFs. The expression profiles of CRFs in different tissues and under various stresses were analyzed in B. oleracea, B. nigra, and B. napus. The similarities and differences in gene sequences and expression profiles among the homologous genes of these species were discussed. In addition, AtCRF11 and its ortholog BrCRF11a were identified to be related to primary root growth in Arabidopsis.

CONCLUSION: This study performed a genome-wide comparative analysis of the CRFs in the diploids and amphidiploids of the Brassica U-triangle species. Many similarities and differences in gene sequences and expression profiles existed among the CRF homologous genes of these species. In the bioinformatics analysis, we found the close relativity of the CRF homologous genes in the Brassica A and C genomes and the distinctiveness of those in the B genome, and the CRF homologous genes in B subgenome were considerably influenced by the A subgenome of B. juncea. In addition, we identified a new function of the Clade V CRFs related to root growth, which also clarified the functional conservation between Arabidopsis and B. rapa. These results not only offer useful information on the functional analysis of CRFs but also provide new insights into the evolution of Brassica species.}, } @article {pmid30285606, year = {2018}, author = {Freudenberg, JM and Dunham, I and Sanseau, P and Rajpal, DK}, title = {Uncovering new disease indications for G-protein coupled receptors and their endogenous ligands.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {345}, pmid = {30285606}, issn = {1471-2105}, mesh = {Disease/*genetics ; Drug Discovery/*methods ; Humans ; *Ligands ; Protein Binding/*physiology ; Receptors, G-Protein-Coupled/*metabolism ; }, abstract = {BACKGROUND: The Open Targets Platform integrates different data sources in order to facilitate identification of potential therapeutic drug targets to treat human diseases. It currently provides evidence for nearly 2.6 million potential target-disease pairs. G-protein coupled receptors are a drug target class of high interest because of the number of successful drugs being developed against them over many years. Here we describe a systematic approach utilizing the Open Targets Platform data to uncover and prioritize potential new disease indications for the G-protein coupled receptors and their ligands.

RESULTS: Utilizing the data available in the Open Targets platform, potential G-protein coupled receptor and endogenous ligand disease association pairs were systematically identified. Intriguing examples such as GPR35 for inflammatory bowel disease and CXCR4 for viral infection are used as illustrations of how a systematic approach can aid in the prioritization of interesting drug discovery hypotheses. Combining evidences for G-protein coupled receptors and their corresponding endogenous peptidergic ligands increases confidence and provides supportive evidence for potential new target-disease hypotheses. Comparing such hypotheses to the global pharma drug discovery pipeline to validate the approach showed that more than 93% of G-protein coupled receptor-disease pairs with a high overall Open Targets score involved receptors with an existing drug discovery program.

CONCLUSIONS: The Open Targets gene-disease score can be used to prioritize potential G-protein coupled receptors-indication hypotheses. In addition, availability of multiple different evidence types markedly increases confidence as does combining evidence from known receptor-ligand pairs. Comparing the top-ranked hypotheses to the current global pharma pipeline serves validation of our approach and identifies and prioritizes new therapeutic opportunities.}, } @article {pmid30285604, year = {2018}, author = {Crescente, JM and Zavallo, D and Helguera, M and Vanzetti, LS}, title = {MITE Tracker: an accurate approach to identify miniature inverted-repeat transposable elements in large genomes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {348}, pmid = {30285604}, issn = {1471-2105}, support = {PNBIO 1131043//Instituto Nacional de Tecnología Agropecuaria/ ; PNBIO 1131022//Instituto Nacional de Tecnología Agropecuaria/ ; }, mesh = {DNA Transposable Elements/*genetics ; Genomics/*methods ; Inverted Repeat Sequences/*genetics ; Oryza/*genetics ; Software ; }, abstract = {BACKGROUND: Miniature inverted-repeat transposable elements (MITEs) are short, non-autonomous class II transposable elements present in a high number of conserved copies in eukaryote genomes. An accurate identification of these elements can help to shed light on the mechanisms controlling genome evolution and gene regulation. The structure and distribution of these elements are well-defined and therefore computational approaches can be used to identify MITEs sequences.

RESULTS: Here we describe MITE Tracker, a novel, open source software program that finds and classifies MITEs using an efficient alignment strategy to retrieve nearby inverted-repeat sequences from large genomes. This program groups them into high sequence homology families using a fast clustering algorithm and finally filters only those elements that were likely transposed from different genomic locations because of their low scoring flanking sequence alignment.

CONCLUSIONS: Many programs have been proposed to find MITEs hidden in genomes. However, none of them are able to process large-scale genomes such as that of bread wheat. Furthermore, in many cases the existing methods perform high false-positive rates (or miss rates). The rice genome was used as reference to compare MITE Tracker against known tools. Our method turned out to be the most reliable in our tests. Indeed, it revealed more known elements, presented the lowest false-positive number and was the only program able to run with the bread wheat genome as input. In wheat, MITE Tracker discovered 6013 MITE families and allowed the first structural exploration of MITEs in the complete bread wheat genome.}, } @article {pmid30285603, year = {2018}, author = {Chen, G and Zou, Y and Hu, J and Ding, Y}, title = {Genome-wide analysis of the rice PPR gene family and their expression profiles under different stress treatments.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {720}, pmid = {30285603}, issn = {1471-2164}, support = {31471464//National Nature Science Foundation of China/ ; 2013CB126900//"973" Program of China/ ; }, mesh = {Chromosomes, Plant/genetics ; Droughts ; *Gene Expression Profiling ; Genome, Plant/genetics ; *Genomics ; Intracellular Space/metabolism ; MicroRNAs/genetics ; Oryza/drug effects/*genetics/metabolism/*physiology ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Protein Transport ; Salts/pharmacology ; Stress, Physiological/drug effects/*genetics ; Synteny ; }, abstract = {BACKGROUND: Pentatricopeptide-repeat proteins (PPRs) are characterized by tandem arrays of a degenerate 35-amino-acid (PPR motifs), which can bind RNA strands and participate in post-transcription. PPR proteins family is one of the largest families in land plants and play important roles in organelle RNA metabolism and plant development. However, the functions of PPR genes involved in biotic and abiotic stresses of rice (Oryza sativa L.) remain largely unknown.

RESULTS: In the present study, a comprehensive genome-wide analysis of PPR genes was performed. A total of 491 PPR genes were found in the rice genome, of which 246 PPR genes belong to the P subfamily, and 245 genes belong to the PLS subfamily. Gene structure analysis showed that most PPR genes lack intron. Chromosomal location analysis indicated that PPR genes were widely distributed in all 12 rice chromosomes. Phylogenetic relationship analysis revealed the distinct difference between the P and PLS subfamilies. Many PPR proteins are predicted to target chloroplasts or mitochondria, and a PPR protein (LOC_Os10g34310) was verified to localize in mitochondria. Furthermore, three PPR genes (LOC_Os03g17634,LOC_Os07g40820,LOC_Os04g51350) were verified as corresponding miRNA targets. The expression pattern analysis showed that many PPR genes could be induced under biotic and abiotic stresses. Finally, seven PPR genes were confirmed with their expression patterns under salinity or drought stress.

CONCLUSIONS: We found 491 PPR genes in the rice genome, and our genes structure analysis and syntenic analysis indicated that PPR genes might be derived from amplification by retro-transposition. The expression pattern present here suggested that PPR proteins have crucial roles in response to different abiotic stresses in rice. Taken together, our study provides a comprehensive analysis of the PPR gene family and will facilitate further studies on their roles in rice growth and development.}, } @article {pmid30285496, year = {2018}, author = {Wallace, JG and Rodgers-Melnick, E and Buckler, ES}, title = {On the Road to Breeding 4.0: Unraveling the Good, the Bad, and the Boring of Crop Quantitative Genomics.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {421-444}, doi = {10.1146/annurev-genet-120116-024846}, pmid = {30285496}, issn = {1545-2948}, abstract = {Understanding the quantitative genetics of crops has been and will continue to be central to maintaining and improving global food security. We outline four stages that plant breeding either has already achieved or will probably soon achieve. Top-of-the-line breeding programs are currently in Breeding 3.0, where inexpensive, genome-wide data coupled with powerful algorithms allow us to start breeding on predicted instead of measured phenotypes. We focus on three major questions that must be answered to move from current Breeding 3.0 practices to Breeding 4.0: (a) How do we adapt crops to better fit agricultural environments? (b) What is the nature of the diversity upon which breeding can act? (c) How do we deal with deleterious variants? Answering these questions and then translating them to actual gains for farmers will be a significant part of achieving global food security in the twenty-first century.}, } @article {pmid30285114, year = {2018}, author = {Pozo, MI and Bartlewicz, J and van Oystaeyen, A and Benavente, A and van Kemenade, G and Wäckers, F and Jacquemyn, H}, title = {Surviving in the absence of flowers: do nectar yeasts rely on overwintering bumblebee queens to complete their annual life cycle?.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy196}, pmid = {30285114}, issn = {1574-6941}, abstract = {Floral nectar represents an ephemeral habitat that is restricted in time and space to zoophilous flowering vegetation. To survive in these habitats, nectar-inhabiting microorganisms rely on animal vectors to disperse from one flower to the next. However, it remains unclear how nectar yeasts persist when flowers and nectar cease to be present. Here, we tested the hypothesis that hibernating bumblebee queens function as a reservoir for nectar yeasts in the absence of plants or pollinators during winter. Our results show that the nectar yeast, Metschnikowia reukaufii, was present in the gastrointestinal tract of wild bumblebee queens that emerged from hibernation and that it could persist inside the gut of hibernating queens under experimental conditions. However, no evidence for such persistence was found in the case of the second most frequent nectar yeast, M. gruessii. Furthermore, a phylloplane yeast that occasionally inhabits nectar, Rhodotorula mucilaginosa, was able to colonize the gut under experimental conditions. Two bumblebee-associated yeasts, Candida bombi and C. bombiphila, were successfully passed down generations after administration in commercial lab-reared bumblebees. Overall, these results demonstrate that bumblebees could act as a reservoir for nectar yeasts during winter when floral nectar is absent.}, } @article {pmid30285095, year = {2018}, author = {Lazarte, JN and Lopez, RP and Ghiringhelli, PD and Berón, CM}, title = {Bacillus wiedmannii biovar thuringiensis: A Specialized Mosquitocidal Pathogen with Plasmids from Diverse Origins.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2823-2833}, pmid = {30285095}, issn = {1759-6653}, abstract = {Bacillus cereus sensu lato also known as B. cereus group is composed of an ecologically diverse bacterial group with an increasing number of related species, some of which are medically or agriculturally important. Numerous efforts have been undertaken to allow presumptive differentiation of B. cereus group species from one another. FCC41 is a Bacillus sp. strain toxic against mosquito species like Aedes aegypti, Aedes (Ochlerotatus) albifasciatus, Culex pipiens, Culex quinquefasciatus, and Culex apicinus, some of them responsible for the transmission of vector-borne diseases. Here, we report the complete genome sequence of FCC41 strain, which consists of one circular chromosome and eight circular plasmids ranging in size from 8 to 490 kb. This strain harbors six crystal protein genes, including cry24Ca, two cry4-like and two cry52-like, a cry41-like parasporin gene and multiple virulence factors. The phylogenetic analysis of the whole-genome sequence of this strain with molecular approaches places this strain into the Bacillus wiedmannii cluster. However, according with phenotypical characteristics such as the mosquitocidal activity due to the presence of Cry proteins found in the parasporal body and cry genes encoded in plasmids of different sizes, indicate that this strain could be renamed as B. wiedmannii biovar thuringiensis strain FCC41.}, } @article {pmid30284733, year = {2018}, author = {Bywater, CL and Wilson, RS and Monro, K and White, CR}, title = {Legs of male fiddler crabs evolved to compensate for claw exaggeration and enhance claw functionality during waving displays.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2491-2502}, doi = {10.1111/evo.13617}, pmid = {30284733}, issn = {1558-5646}, abstract = {Many exaggerated morphological traits evolve under sexual selection. However, the optimal level of exaggeration is dictated by a trade-off between natural and sexual selection, representing a balance between its benefits and associated costs. Male fiddler crabs wave an enlarged major claw during behavioural displays that eliminates the need for direct combat, and determines courtship outcomes. The outcomes of these displays often depend on claw size, exposing males to selection for larger claws to improve mating and combat success. Applying phylogenetic comparative methods to 27 fiddler crab species, we examined the evolution of major claw morphologies, leg morphologies, and waving displays to determine whether these traits coevolved to optimise functioning of the exaggerated claw, or to mitigate potential metabolic or locomotor costs. We found legs to be sexually dimorphic, with males having longer legs than females. Legs were also longer in species that waved laterally rather than vertically, in species with larger major claws, and in species whose major claws were relatively elongate. These results suggest that leg morphology has coevolved with claw enlargement to enhance functionality of the major claw during waving displays, in addition to compensating for any negative effects of claw size.}, } @article {pmid30284242, year = {2018}, author = {Stitzer, MC and Brand, P}, title = {Digest: Hybrid incompatibilities and introgression in wild monkeyflowers.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2565-2566}, doi = {10.1111/evo.13616}, pmid = {30284242}, issn = {1558-5646}, abstract = {How are alleles that are detrimental to fitness maintained in natural populations? Zuellig and Sweigart (2018a) find that alleles from a two-locus hybrid incompatibility system segregate at considerable frequencies in two species of monkeyflowers, suggesting that despite providing a fitness cost, these alleles remain polymorphic as a consequence of gene flow between the two species. The system provides the potential to understand the evolutionary trajectory of hybrid incompatibilities and their role in speciation.}, } @article {pmid30283991, year = {2018}, author = {Atac, N and Kurt-Azap, O and Dolapci, I and Yesilkaya, A and Ergonul, O and Gonen, M and Can, F}, title = {The Role of AcrAB-TolC Efflux Pumps on Quinolone Resistance of E. coli ST131.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1661-1666}, pmid = {30283991}, issn = {1432-0991}, mesh = {Anti-Bacterial Agents/pharmacology ; Carrier Proteins/*genetics ; Drug Resistance, Multiple, Bacterial/*genetics ; Escherichia coli/*drug effects/*genetics ; Escherichia coli Infections/drug therapy ; Escherichia coli Proteins/*genetics ; Humans ; Microbial Sensitivity Tests/methods ; Multilocus Sequence Typing/methods ; Quinolones/*pharmacology ; Virulence Factors/genetics ; }, abstract = {Escherichia coli ST131 is a cause for global concern because of its high multidrug resistance and several virulence factors. In this study, the contribution of acrAB-TolC efflux system of E. coli ST131 to fluoroquinolone resistance was evaluated. A total of nonrepetitive 111 ciprofloxacin-resistant E. coli isolates were included in the study. Multilocus sequence typing was used for genotyping. Expressions of acrA, acrB, and TolC efflux pump genes were measured by RT-PCR. Mutations in marA, gyrA, parC, and aac(6')-lb-cr positivity were studied by Sanger sequencing. Sixty-four (57.7%) of the isolates were classified as ST131, and 52 (81.3%) of the ST131 isolates belonged to H30-Rx subclone. In ST131, CTX-M 15 positivity (73%) and aac(6')-lb-cr carriage (75%) were significantly higher than those in non-ST131 (12.8% and 51%, respectively) (P < 0.05). The ampicillin-sulbactam (83%) resistance was higher, and gentamicin resistance (20%) was lower in ST131 than that in non-ST131 (64% and 55%, respectively) (P = 0.001 and P = 0.0002). Numbers of the isolates with MDR or XDR profiles did not differ in both groups. Multiple in-dels (up to 16) were recorded in all quinolone-resistant isolates. However, marA gene was more overexpressed in ST131 compared to that in non-ST131 (median 5.98 vs. 3.99; P = 0.0007). Belonging to H30-Rx subclone, isolation site, ciprofloxacin MIC values did not correlate with efflux pump expressions. In conclusion, the marA regulatory gene of AcrAB-TolC efflux pump system has a significant impact on quinolone resistance and progression to MDR profile in ST131 clone. Efflux pump inhibitors might be alternative drugs for the treatment of infections caused by E. coli ST131 if used synergistically in combination with antibiotics.}, } @article {pmid30283979, year = {2018}, author = {Puzakov, MV and Puzakova, LV and Cheresiz, SV}, title = {An Analysis of IS630/Tc1/mariner Transposons in the Genome of a Pacific Oyster, Crassostrea gigas.}, journal = {Journal of molecular evolution}, volume = {86}, number = {8}, pages = {566-580}, pmid = {30283979}, issn = {1432-1432}, support = {AAAA-A18-118021490093-4//Russian Academy of Sciences/ ; }, abstract = {Transposable elements represent the DNA fragments capable of increasing their copy number and moving within the genome. Class II mobile elements represents the DNA transposons, which transpose via excision and the subsequent reinsertion at random genomic loci. The increase of their copy number occurs only when the transposition event is coupled with the replication. IS630/Tc1/mariner DNA transposon superfamily is one of the largest and widely distributed among the Class II elements. In this work, we provide a detailed analysis of IS630/Tc1/mariner DNA transposons from the Pacific oyster, Crassostrea gigas. IS630/Tc1/mariner transposons represented in the genome of the Pacific oyster belong to four families, Tc1 (DD34E), mariner (DD34D), pogo (DDxD), and rosa (DD41D). More than a half of IS630/Tc1/mariner elements from C. gigas belong to Tc1 family. Furthermore, Mariner-31_CGi element was shown to represent a new and previously unknown family with DD37E signature. We also discovered the full-size transcripts of eight elements from Tc1, mariner, and pogo families, three of which can, presumably, retain their transposition activity.}, } @article {pmid30283141, year = {2018}, author = {, and , and , and , and , and , and , and , and , and , }, title = {Single-cell transcriptomics of 20 mouse organs creates a Tabula Muris.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {367-372}, doi = {10.1038/s41586-018-0590-4}, pmid = {30283141}, issn = {1476-4687}, support = {DP1 LM012179/LM/NLM NIH HHS/United States ; P01 AG036695/AG/NIA NIH HHS/United States ; R01 AR073248/AR/NIAMS NIH HHS/United States ; DP1 AG053015/AG/NIA NIH HHS/United States ; R37 AG023806/AG/NIA NIH HHS/United States ; K08 DK101603/DK/NIDDK NIH HHS/United States ; I01 RX001222/RX/RRD VA/United States ; I01 BX002324/BX/BLRD VA/United States ; }, abstract = {Here we present a compendium of single-cell transcriptomic data from the model organism Mus musculus that comprises more than 100,000 cells from 20 organs and tissues. These data represent a new resource for cell biology, reveal gene expression in poorly characterized cell populations and enable the direct and controlled comparison of gene expression in cell types that are shared between tissues, such as T lymphocytes and endothelial cells from different anatomical locations. Two distinct technical approaches were used for most organs: one approach, microfluidic droplet-based 3'-end counting, enabled the survey of thousands of cells at relatively low coverage, whereas the other, full-length transcript analysis based on fluorescence-activated cell sorting, enabled the characterization of cell types with high sensitivity and coverage. The cumulative data provide the foundation for an atlas of transcriptomic cell biology.}, } @article {pmid30283140, year = {2018}, author = {Du, M and Yuan, Z and Yu, H and Henderson, N and Sarowar, S and Zhao, G and Werneburg, GT and Thanassi, DG and Li, H}, title = {Handover mechanism of the growing pilus by the bacterial outer-membrane usher FimD.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {444-447}, doi = {10.1038/s41586-018-0587-z}, pmid = {30283140}, issn = {1476-4687}, support = {R01 GM062987/GM/NIGMS NIH HHS/United States ; R01 GM111742/GM/NIGMS NIH HHS/United States ; }, abstract = {Pathogenic bacteria such as Escherichia coli assemble surface structures termed pili, or fimbriae, to mediate binding to host-cell receptors1. Type 1 pili are assembled via the conserved chaperone-usher pathway2-5. The outer-membrane usher FimD recruits pilus subunits bound by the chaperone FimC via the periplasmic N-terminal domain of the usher. Subunit translocation through the β-barrel channel of the usher occurs at the two C-terminal domains (which we label CTD1 and CTD2) of this protein. How the chaperone-subunit complex bound to the N-terminal domain is handed over to the C-terminal domains, as well as the timing of subunit polymerization into the growing pilus, have previously been unclear. Here we use cryo-electron microscopy to capture a pilus assembly intermediate (FimD-FimC-FimF-FimG-FimH) in a conformation in which FimD is in the process of handing over the chaperone-bound end of the growing pilus to the C-terminal domains. In this structure, FimF has already polymerized with FimG, and the N-terminal domain of FimD swings over to bind CTD2; the N-terminal domain maintains contact with FimC-FimF, while at the same time permitting access to the C-terminal domains. FimD has an intrinsically disordered N-terminal tail that precedes the N-terminal domain. This N-terminal tail folds into a helical motif upon recruiting the FimC-subunit complex, but reorganizes into a loop to bind CTD2 during handover. Because both the N-terminal and C-terminal domains of FimD are bound to the end of the growing pilus, the structure further suggests a mechanism for stabilizing the assembly intermediate to prevent the pilus fibre diffusing away during the incorporation of thousands of subunits.}, } @article {pmid30283139, year = {2018}, author = {Lin, Z and Liu, Y and Halim, U and Ding, M and Liu, Y and Wang, Y and Jia, C and Chen, P and Duan, X and Wang, C and Song, F and Li, M and Wan, C and Huang, Y and Duan, X}, title = {Solution-processable 2D semiconductors for high-performance large-area electronics.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {254-258}, doi = {10.1038/s41586-018-0574-4}, pmid = {30283139}, issn = {1476-4687}, support = {DE-SC0018828//US Department of Energy/International ; EFRI-1433541//National Science Foundation/International ; }, abstract = {Two-dimensional (2D) materials, consisting of atomically thin crystal layers bound by the van der Waals force, have attracted much interest because of their potential in diverse technologies, including electronics, optoelectronics and catalysis1-10. In particular, solution-processable 2D semiconductor (such as MoS2) nanosheets are attractive building blocks for large-area thin-film electronics. In contrast to conventional zero- and one-dimensional nanostructures (quantum dots and nanowires, respectively), which are typically plagued by surface dangling bonds and associated trapping states, 2D nanosheets have dangling-bond-free surfaces. Thin films created by stacking multiple nanosheets have atomically clean van der Waals interfaces and thus promise excellent charge transport11-15. However, preparing high-quality solution-processable 2D semiconductor nanosheets remains a challenge. For example, MoS2 nanosheets and thin films produced using lithium intercalation and exfoliation are plagued by the presence of the metallic 1T phase and poor electrical performance (mobilities of about 0.3 square centimetres per volt per second and on/off ratios of less than 10)2,12, and materials produced by liquid exfoliation exhibit an intrinsically broad thickness distribution, which leads to poor film quality and unsatisfactory thin-film electrical performance (mobilities of about 0.4 square centimetres per volt per second and on/off ratios of about 100)14,16,17. Here we report a general approach to preparing highly uniform, solution-processable, phase-pure semiconducting nanosheets, which involves the electrochemical intercalation of quaternary ammonium molecules (such as tetraheptylammonium bromide) into 2D crystals, followed by a mild sonication and exfoliation process. By precisely controlling the intercalation chemistry, we obtained phase-pure, semiconducting 2H-MoS2 nanosheets with a narrow thickness distribution. These nanosheets were then further processed into high-performance thin-film transistors, with room-temperature mobilities of about 10 square centimetres per volt per second and on/off ratios of 106 that greatly exceed those obtained for previous solution-processed MoS2 thin-film transistors. The scalable fabrication of large-area arrays of thin-film transistors enabled the construction of functional logic gates and computational circuits, including an inverter, NAND, NOR, AND and XOR gates, and a logic half-adder. We also applied our approach to other 2D materials, including WSe2, Bi2Se3, NbSe2, In2Se3, Sb2Te3 and black phosphorus, demonstrating its potential for generating versatile solution-processable 2D materials.}, } @article {pmid30283138, year = {2018}, author = {Borducchi, EN and Liu, J and Nkolola, JP and Cadena, AM and Yu, WH and Fischinger, S and Broge, T and Abbink, P and Mercado, NB and Chandrashekar, A and Jetton, D and Peter, L and McMahan, K and Moseley, ET and Bekerman, E and Hesselgesser, J and Li, W and Lewis, MG and Alter, G and Geleziunas, R and Barouch, DH}, title = {Antibody and TLR7 agonist delay viral rebound in SHIV-infected monkeys.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {360-364}, pmid = {30283138}, issn = {1476-4687}, support = {UM1 AI126603/AI/NIAID NIH HHS/United States ; U19 AI096040/AI/NIAID NIH HHS/United States ; R01 OD024917/OD/NIH HHS/United States ; UM1 AI124377/AI/NIAID NIH HHS/United States ; U19 AI128751/AI/NIAID NIH HHS/United States ; R01 AI129797/AI/NIAID NIH HHS/United States ; }, abstract = {The latent viral reservoir is the critical barrier for the development of a cure for HIV-1 infection. Previous studies have shown direct antiviral activity of potent HIV-1 Env-specific broadly neutralizing antibodies (bNAbs) administered when antiretroviral therapy (ART) was discontinued, but it remains unclear whether bNAbs can target the viral reservoir during ART. Here we show that administration of the V3 glycan-dependent bNAb PGT121 together with the Toll-like receptor 7 (TLR7) agonist vesatolimod (GS-9620) during ART delayed viral rebound following discontinuation of ART in simian-human immunodeficiency virus (SHIV)-SF162P3-infected rhesus monkeys in which ART was initiated during early acute infection. Moreover, in the subset of monkeys that were treated with both PGT121 and GS-9620 and that did not show viral rebound after discontinuation of ART, adoptive transfer studies and CD8-depletion studies also did not reveal virus. These data demonstrate the potential of bNAb administration together with innate immune stimulation as a possible strategy for targeting the viral reservoir.}, } @article {pmid30283137, year = {2018}, author = {Reich, PB and Sendall, KM and Stefanski, A and Rich, RL and Hobbie, SE and Montgomery, RA}, title = {Effects of climate warming on photosynthesis in boreal tree species depend on soil moisture.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {263-267}, doi = {10.1038/s41586-018-0582-4}, pmid = {30283137}, issn = {1476-4687}, support = {FG02-07ER64456//US Department of Energy/International ; }, abstract = {Climate warming will influence photosynthesis via thermal effects and by altering soil moisture1-11. Both effects may be important for the vast areas of global forests that fluctuate between periods when cool temperatures limit photosynthesis and periods when soil moisture may be limiting to carbon gain4-6,9-11. Here we show that the effects of climate warming flip from positive to negative as southern boreal forests transition from rainy to modestly dry periods during the growing season. In a three-year open-air warming experiment with juveniles of 11 temperate and boreal tree species, an increase of 3.4 °C in temperature increased light-saturated net photosynthesis and leaf diffusive conductance on average on the one-third of days with the wettest soils. In all 11 species, leaf diffusive conductance and, as a result, light-saturated net photosynthesis decreased during dry spells, and did so more sharply in warmed plants than in plants at ambient temperatures. Consequently, across the 11 species, warming reduced light-saturated net photosynthesis on the two-thirds of days with driest soils. Thus, low soil moisture may reduce, or even reverse, the potential benefits of climate warming on photosynthesis in mesic, seasonally cold environments, both during drought and in regularly occurring, modestly dry periods during the growing season.}, } @article {pmid30283136, year = {2018}, author = {Zhang, J and Zhang, M and Acampora, D and Vojtek, M and Yuan, D and Simeone, A and Chambers, I}, title = {OTX2 restricts entry to the mouse germline.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {595-599}, doi = {10.1038/s41586-018-0581-5}, pmid = {30283136}, issn = {1476-4687}, abstract = {The successful segregation of germ cells from somatic lineages is vital for sexual reproduction and species survival. In the mouse, primordial germ cells (PGCs), precursors of all germ cells, are induced from the post-implantation epiblast1. Induction requires BMP4 signalling to prospective PGCs2 and the intrinsic action of PGC transcription factors3-6. However, the molecular mechanisms that connect BMP4 to induction of the PGC transcription factors that are responsible for segregating PGCs from somatic lineages are unknown. Here we show that the transcription factor OTX2 is a key regulator of these processes. Downregulation of Otx2 precedes the initiation of the PGC programme both in vitro and in vivo. Deletion of Otx2 in vitro markedly increases the efficiency of PGC-like cell differentiation and prolongs the period of PGC competence. In the absence of Otx2 activity, differentiation of PGC-like cells becomes independent of the otherwise essential cytokine signals, with germline entry initiating even in the absence of the PGC transcription factor BLIMP1. Deletion of Otx2 in vivo increases PGC numbers. These data demonstrate that OTX2 functions repressively upstream of PGC transcription factors, acting as a roadblock to limit entry of epiblast cells to the germline to a small window in space and time, thereby ensuring correct numerical segregation of germline cells from the soma.}, } @article {pmid30283135, year = {2018}, author = {Schmidt, F and Cherepkova, MY and Platt, RJ}, title = {Transcriptional recording by CRISPR spacer acquisition from RNA.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {380-385}, doi = {10.1038/s41586-018-0569-1}, pmid = {30283135}, issn = {1476-4687}, abstract = {The ability to record transcriptional events within a cell over time would help to elucidate how molecular events give rise to complex cellular behaviours and states. However, current molecular recording technologies capture only a small set of defined stimuli. Here we use CRISPR spacer acquisition to capture and convert intracellular RNAs into DNA, enabling DNA-based storage of transcriptional information. In Escherichia coli, we show that defined stimuli, such as an RNA virus or arbitrary sequences, as well as complex stimuli, such as oxidative stress, result in quantifiable transcriptional records that are stored within a population of cells. We demonstrate that the transcriptional records enable us to classify and describe complex cellular behaviours and to identify the precise genes that orchestrate differential cellular responses. In the future, CRISPR spacer acquisition-mediated recording of RNA followed by deep sequencing (Record-seq) could be used to reconstruct transcriptional histories that describe complex cell behaviours or pathological states.}, } @article {pmid30283134, year = {2018}, author = {Beccari, L and Moris, N and Girgin, M and Turner, DA and Baillie-Johnson, P and Cossy, AC and Lutolf, MP and Duboule, D and Arias, AM}, title = {Multi-axial self-organization properties of mouse embryonic stem cells into gastruloids.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {272-276}, doi = {10.1038/s41586-018-0578-0}, pmid = {30283134}, issn = {1476-4687}, support = {//European Research Council/International ; }, abstract = {The emergence of multiple axes is an essential element in the establishment of the mammalian body plan. This process takes place shortly after implantation of the embryo within the uterus and relies on the activity of gene regulatory networks that coordinate transcription in space and time. Whereas genetic approaches have revealed important aspects of these processes1, a mechanistic understanding is hampered by the poor experimental accessibility of early post-implantation stages. Here we show that small aggregates of mouse embryonic stem cells (ESCs), when stimulated to undergo gastrulation-like events and elongation in vitro, can organize a post-occipital pattern of neural, mesodermal and endodermal derivatives that mimic embryonic spatial and temporal gene expression. The establishment of the three major body axes in these 'gastruloids'2,3 suggests that the mechanisms involved are interdependent. Specifically, gastruloids display the hallmarks of axial gene regulatory systems as exemplified by the implementation of collinear Hox transcriptional patterns along an extending antero-posterior axis. These results reveal an unanticipated self-organizing capacity of aggregated ESCs and suggest that gastruloids could be used as a complementary system to study early developmental events in the mammalian embryo.}, } @article {pmid30283133, year = {2018}, author = {Ma, D and Wang, Z and Merrikh, CN and Lang, KS and Lu, P and Li, X and Merrikh, H and Rao, Z and Xu, W}, title = {Crystal structure of a membrane-bound O-acyltransferase.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {286-290}, doi = {10.1038/s41586-018-0568-2}, pmid = {30283133}, issn = {1476-4687}, support = {DP2 GM110773/GM/NIGMS NIH HHS/United States ; R01 GM127316/GM/NIGMS NIH HHS/United States ; }, abstract = {Membrane-bound O-acyltransferases (MBOATs) are a superfamily of integral transmembrane enzymes that are found in all kingdoms of life1. In bacteria, MBOATs modify protective cell-surface polymers. In vertebrates, some MBOAT enzymes-such as acyl-coenzyme A:cholesterol acyltransferase and diacylglycerol acyltransferase 1-are responsible for lipid biosynthesis or phospholipid remodelling2,3. Other MBOATs, including porcupine, hedgehog acyltransferase and ghrelin acyltransferase, catalyse essential lipid modifications of secreted proteins such as Wnt, hedgehog and ghrelin, respectively4-10. Although many MBOAT proteins are important drug targets, little is known about their molecular architecture and functional mechanisms. Here we present crystal structures of DltB, an MBOAT responsible for the D-alanylation of cell-wall teichoic acid in Gram-positive bacteria11-16, both alone and in complex with the D-alanyl donor protein DltC. DltB contains a ring of 11 peripheral transmembrane helices, which shield a highly conserved extracellular structural funnel extending into the middle of the lipid bilayer. The conserved catalytic histidine residue is located at the bottom of this funnel and is connected to the intracellular DltC through a narrow tunnel. Mutation of either the catalytic histidine or the DltC-binding site of DltB abolishes the D-alanylation of lipoteichoic acid and sensitizes the Gram-positive bacterium Bacillus subtilis to cell-wall stress, which suggests cross-membrane catalysis involving the tunnel. Structure-guided sequence comparison among DltB and vertebrate MBOATs reveals a conserved structural core and suggests that MBOATs from different organisms have similar catalytic mechanisms. Our structures provide a template for understanding structure-function relationships in MBOATs and for developing therapeutic MBOAT inhibitors.}, } @article {pmid30283132, year = {2018}, author = {Akıl, C and Robinson, RC}, title = {Genomes of Asgard archaea encode profilins that regulate actin.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {439-443}, doi = {10.1038/s41586-018-0548-6}, pmid = {30283132}, issn = {1476-4687}, abstract = {The origin of the eukaryotic cell is unresolved1,2. Metagenomics sequencing has recently identified several potential eukaryotic gene homologues in Asgard archaea3,4, consistent with the hypothesis that the eukaryotic cell evolved from within the Archaea domain. However, many of these eukaryotic-like sequences are highly divergent and the organisms have yet to be imaged or cultivated, which brings into question the extent to which these archaeal proteins represent functional equivalents of their eukaryotic counterparts. Here we show that Asgard archaea encode functional profilins and thereby establish that this archaeal superphylum has a regulated actin cytoskeleton, one of the hallmarks of the eukaryotic cell5. Loki profilin-1, Loki profilin-2 and Odin profilin adopt the typical profilin fold and are able to interact with rabbit actin-an interaction that involves proteins from species that diverged more than 1.2 billion years ago6. Biochemical experiments reveal that mammalian actin polymerizes in the presence of Asgard profilins; however, Loki, Odin and Heimdall profilins impede pointed-end elongation. These archaeal profilins also retard the spontaneous nucleation of actin filaments, an effect that is reduced in the presence of phospholipids. Asgard profilins do not interact with polyproline motifs and the profilin-polyproline interaction therefore probably evolved later in the Eukarya lineage. These results suggest that Asgard archaea possess a primordial, polar, profilin-regulated actin system, which may be localized to membranes owing to the sensitivity of Asgard profilins to phospholipids. Because Asgard archaea are also predicted to encode potential eukaryotic-like genes involved in membrane-trafficking and endocytosis3,4, imaging is now necessary to elucidate whether these organisms are capable of generating eukaryotic-like membrane dynamics that are regulated by actin, such as are observed in eukaryotic cell movement, podosomes and endocytosis.}, } @article {pmid30283128, year = {2018}, author = {Savage, N}, title = {Expanding the reach of science.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S10-S11}, doi = {10.1038/d41586-018-06833-z}, pmid = {30283128}, issn = {1476-4687}, } @article {pmid30283127, year = {2018}, author = {Singh Chawla, D}, title = {Making children safer online.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S15-S16}, doi = {10.1038/d41586-018-06848-6}, pmid = {30283127}, issn = {1476-4687}, } @article {pmid30283126, year = {2018}, author = {Hatch, J}, title = {Better teachers are needed to improve science education.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S2-S4}, doi = {10.1038/d41586-018-06830-2}, pmid = {30283126}, issn = {1476-4687}, } @article {pmid30283125, year = {2018}, author = {Jones, N}, title = {Boosting the number of students from underrepresented groups in physics.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S12-S14}, doi = {10.1038/d41586-018-06834-y}, pmid = {30283125}, issn = {1476-4687}, } @article {pmid30283124, year = {2018}, author = {Owens, B}, title = {Science and technology education.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S1}, doi = {10.1038/d41586-018-06829-9}, pmid = {30283124}, issn = {1476-4687}, } @article {pmid30283123, year = {2018}, author = {Garramon Merkle, B}, title = {Drawn to science.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S8-S9}, doi = {10.1038/d41586-018-06832-0}, pmid = {30283123}, issn = {1476-4687}, } @article {pmid30283122, year = {2018}, author = {Jones, N}, title = {Simulated labs are booming.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S5-S7}, doi = {10.1038/d41586-018-06831-1}, pmid = {30283122}, issn = {1476-4687}, } @article {pmid30283121, year = {2018}, author = {Durose, C and Richardson, L and Perry, B}, title = {Craft metrics to value co-production.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {32-33}, doi = {10.1038/d41586-018-06860-w}, pmid = {30283121}, issn = {1476-4687}, } @article {pmid30283120, year = {2018}, author = {Willyard, C and Scudellari, M and Nordling, L}, title = {How three research groups are tearing down the ivory tower.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {24-28}, doi = {10.1038/d41586-018-06858-4}, pmid = {30283120}, issn = {1476-4687}, mesh = {Authorship ; *Biodiversity ; Child, Preschool ; *City Planning ; Climate Change ; *Community-Based Participatory Research ; Farmers ; Food Supply ; Health Promotion ; *Healthy Diet ; Humans ; Indians, North American ; Patient Participation ; Rain ; Sanitation ; *Stakeholder Participation ; Water Supply ; *Workforce ; Zambia ; }, } @article {pmid30283119, year = {2018}, author = {}, title = {The best research is produced when researchers and communities work together.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {7}, doi = {10.1038/d41586-018-06855-7}, pmid = {30283119}, issn = {1476-4687}, mesh = {*Research ; *Research Personnel ; }, } @article {pmid30283118, year = {2018}, author = {}, title = {Science shared.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {23}, doi = {10.1038/d41586-018-06859-3}, pmid = {30283118}, issn = {1476-4687}, mesh = {Caregivers ; Farmers ; Financing, Organized ; Humans ; *Patient Participation ; Patients ; *Research ; *Stakeholder Participation ; *Workforce ; }, } @article {pmid30283117, year = {2018}, author = {Hickey, G and Richards, T and Sheehy, J}, title = {Co-production from proposal to paper.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {29-31}, doi = {10.1038/d41586-018-06861-9}, pmid = {30283117}, issn = {1476-4687}, mesh = {Child ; Clinical Trials as Topic/economics ; Feedback ; Financing, Organized ; HIV Infections/drug therapy ; Humans ; *Patient Advocacy ; *Patient Participation ; Peer Review, Research/methods ; Regenerative Medicine/economics ; *Research ; *Stakeholder Participation ; *Workforce ; }, } @article {pmid30283116, year = {2018}, author = {Kiser, B}, title = {An ode to female space trainees, the creeping cost of climate change, and the fabric of history: Books in brief.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {35}, doi = {10.1038/d41586-018-06862-8}, pmid = {30283116}, issn = {1476-4687}, } @article {pmid30283115, year = {2018}, author = {Smaglik, P}, title = {Beating the odds to secure a permanent contract.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {S49-S51}, doi = {10.1038/d41586-018-06873-5}, pmid = {30283115}, issn = {1476-4687}, } @article {pmid30283114, year = {2018}, author = {}, title = {CERN's physics uproar, quantum-satellite plans and Yellowstone grizzly protections.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {12-13}, doi = {10.1038/d41586-018-06857-5}, pmid = {30283114}, issn = {1476-4687}, } @article {pmid30283113, year = {2018}, author = {}, title = {US Supreme Court should prevent execution of murderer who no longer remembers his crime.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {7-8}, doi = {10.1038/d41586-018-06916-x}, pmid = {30283113}, issn = {1476-4687}, mesh = {Capital Punishment/*legislation & jurisprudence ; Dementia, Vascular/*psychology ; History, 20th Century ; Homicide/history/*legislation & jurisprudence ; Humans ; Male ; Memory, Episodic ; Prisoners/history/*legislation & jurisprudence/*psychology ; Punishment/*psychology ; *Supreme Court Decisions ; United States ; }, } @article {pmid30283112, year = {2018}, author = {Nikel, W}, title = {Cerise sky memories.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {158}, doi = {10.1038/d41586-018-06874-4}, pmid = {30283112}, issn = {1476-4687}, } @article {pmid30283111, year = {2018}, author = {Cohen, RE}, title = {Ferroelectric polymers morph into action.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {48-49}, doi = {10.1038/d41586-018-06865-5}, pmid = {30283111}, issn = {1476-4687}, mesh = {*Physics ; *Polymers ; }, } @article {pmid30283110, year = {2018}, author = {Harris, J and Kotiaho, JS}, title = {New jargon seeping slowly into biodiversity world.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {39}, doi = {10.1038/d41586-018-06893-1}, pmid = {30283110}, issn = {1476-4687}, } @article {pmid30283109, year = {2018}, author = {Lin, J}, title = {China's electricity switch won't be swift or painless.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {39}, doi = {10.1038/d41586-018-06894-0}, pmid = {30283109}, issn = {1476-4687}, } @article {pmid30283108, year = {2018}, author = {Anderson, V and Jones, A and Read, R}, title = {United Kingdom should learn from global body for biodiversity.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {39}, doi = {10.1038/d41586-018-06892-2}, pmid = {30283108}, issn = {1476-4687}, mesh = {*Biodiversity ; Economics ; *Sociology ; United Kingdom ; }, } @article {pmid30283107, year = {2018}, author = {Leroy, G and Bonnett, BN and Mäki, K}, title = {Don't dismiss pet genomics - tests help breeders.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {39}, doi = {10.1038/d41586-018-06891-3}, pmid = {30283107}, issn = {1476-4687}, } @article {pmid30283106, year = {2018}, author = {Abeysekara, AU and Albert, A and Alfaro, R and Alvarez, C and Álvarez, JD and Arceo, R and Arteaga-Velázquez, JC and Avila Rojas, D and Ayala Solares, HA and Belmont-Moreno, E and BenZvi, SY and Brisbois, C and Caballero-Mora, KS and Capistrán, T and Carramiñana, A and Casanova, S and Castillo, M and Cotti, U and Cotzomi, J and Coutiño de León, S and De León, C and De la Fuente, E and Díaz-Vélez, JC and Dichiara, S and Dingus, BL and DuVernois, MA and Ellsworth, RW and Engel, K and Espinoza, C and Fang, K and Fleischhack, H and Fraija, N and Galván-Gámez, A and García-González, JA and Garfias, F and González-Muñoz, A and González, MM and Goodman, JA and Hampel-Arias, Z and Harding, JP and Hernandez, S and Hinton, J and Hona, B and Hueyotl-Zahuantitla, F and Hui, CM and Hüntemeyer, P and Iriarte, A and Jardin-Blicq, A and Joshi, V and Kaufmann, S and Kar, P and Kunde, GJ and Lauer, RJ and Lee, WH and León Vargas, H and Li, H and Linnemann, JT and Longinotti, AL and Luis-Raya, G and López-Coto, R and Malone, K and Marinelli, SS and Martinez, O and Martinez-Castellanos, I and Martínez-Castro, J and Matthews, JA and Miranda-Romagnoli, P and Moreno, E and Mostafá, M and Nayerhoda, A and Nellen, L and Newbold, M and Nisa, MU and Noriega-Papaqui, R and Pretz, J and Pérez-Pérez, EG and Ren, Z and Rho, CD and Rivière, C and Rosa-González, D and Rosenberg, M and Ruiz-Velasco, E and Salesa Greus, F and Sandoval, A and Schneider, M and Schoorlemmer, H and Seglar Arroyo, M and Sinnis, G and Smith, AJ and Springer, RW and Surajbali, P and Taboada, I and Tibolla, O and Tollefson, K and Torres, I and Vianello, G and Villaseñor, L and Weisgarber, T and Werner, F and Westerhoff, S and Wood, J and Yapici, T and Yodh, G and Zepeda, A and Zhang, H and Zhou, H}, title = {Very-high-energy particle acceleration powered by the jets of the microquasar SS 433.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {82-85}, doi = {10.1038/s41586-018-0565-5}, pmid = {30283106}, issn = {1476-4687}, abstract = {SS 433 is a binary system containing a supergiant star that is overflowing its Roche lobe with matter accreting onto a compact object (either a black hole or neutron star)1-3. Two jets of ionized matter with a bulk velocity of approximately 0.26c (where c is the speed of light in vacuum) extend from the binary, perpendicular to the line of sight, and terminate inside W50, a supernova remnant that is being distorted by the jets2,4-8. SS 433 differs from other microquasars (small-scale versions of quasars that are present within our own Galaxy) in that the accretion is believed to be super-Eddington9-11, and the luminosity of the system is about 1040 ergs per second2,9,12,13. The lobes of W50 in which the jets terminate, about 40 parsecs from the central source, are expected to accelerate charged particles, and indeed radio and X-ray emission consistent with electron synchrotron emission in a magnetic field have been observed14-16. At higher energies (greater than 100 gigaelectronvolts), the particle fluxes of γ-rays from X-ray hotspots around SS 433 have been reported as flux upper limits6,17-20. In this energy regime, it has been unclear whether the emission is dominated by electrons that are interacting with photons from the cosmic microwave background through inverse-Compton scattering or by protons that are interacting with the ambient gas. Here we report teraelectronvolt γ-ray observations of the SS 433/W50 system that spatially resolve the lobes. The teraelectronvolt emission is localized to structures in the lobes, far from the centre of the system where the jets are formed. We have measured photon energies of at least 25 teraelectronvolts, and these are certainly not Doppler-boosted, because of the viewing geometry. We conclude that the emission-from radio to teraelectronvolt energies-is consistent with a single population of electrons with energies extending to at least hundreds of teraelectronvolts in a magnetic field of about 16 microgauss.}, } @article {pmid30283105, year = {2018}, author = {Buermann, W and Forkel, M and O'Sullivan, M and Sitch, S and Friedlingstein, P and Haverd, V and Jain, AK and Kato, E and Kautz, M and Lienert, S and Lombardozzi, D and Nabel, JEMS and Tian, H and Wiltshire, AJ and Zhu, D and Smith, WK and Richardson, AD}, title = {Widespread seasonal compensation effects of spring warming on northern plant productivity.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {110-114}, doi = {10.1038/s41586-018-0555-7}, pmid = {30283105}, issn = {1476-4687}, abstract = {Climate change is shifting the phenological cycles of plants1, thereby altering the functioning of ecosystems, which in turn induces feedbacks to the climate system2. In northern (north of 30° N) ecosystems, warmer springs lead generally to an earlier onset of the growing season3,4 and increased ecosystem productivity early in the season5. In situ6 and regional7-9 studies also provide evidence for lagged effects of spring warmth on plant productivity during the subsequent summer and autumn. However, our current understanding of these lagged effects, including their direction (beneficial or adverse) and geographic distribution, is still very limited. Here we analyse satellite, field-based and modelled data for the period 1982-2011 and show that there are widespread and contrasting lagged productivity responses to spring warmth across northern ecosystems. On the basis of the observational data, we find that roughly 15 per cent of the total study area of about 41 million square kilometres exhibits adverse lagged effects and that roughly 5 per cent of the total study area exhibits beneficial lagged effects. By contrast, current-generation terrestrial carbon-cycle models predict much lower areal fractions of adverse lagged effects (ranging from 1 to 14 per cent) and much higher areal fractions of beneficial lagged effects (ranging from 9 to 54 per cent). We find that elevation and seasonal precipitation patterns largely dictate the geographic pattern and direction of the lagged effects. Inadequate consideration in current models of the effects of the seasonal build-up of water stress on seasonal vegetation growth may therefore be able to explain the differences that we found between our observation-constrained estimates and the model-constrained estimates of lagged effects associated with spring warming. Overall, our results suggest that for many northern ecosystems the benefits of warmer springs on growing-season ecosystem productivity are effectively compensated for by the accumulation of seasonal water deficits, despite the fact that northern ecosystems are thought to be largely temperature- and radiation-limited10.}, } @article {pmid30283104, year = {2018}, author = {Bertone, G and Tait, TMP}, title = {A new era in the search for dark matter.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {51-56}, doi = {10.1038/s41586-018-0542-z}, pmid = {30283104}, issn = {1476-4687}, support = {PHY-1316792//National Science Foundation/International ; }, abstract = {There is a growing sense of 'crisis' in the dark-matter particle community, which arises from the absence of evidence for the most popular candidates for dark-matter particles-such as weakly interacting massive particles, axions and sterile neutrinos-despite the enormous effort that has gone into searching for these particles. Here we discuss what we have learned about the nature of dark matter from past experiments and the implications for planned dark-matter searches in the next decade. We argue that diversifying the experimental effort and incorporating astronomical surveys and gravitational-wave observations is our best hope of making progress on the dark-matter problem.}, } @article {pmid30283103, year = {2018}, author = {Leonard, DJ and Ward, JW and Clayden, J}, title = {Asymmetric α-arylation of amino acids.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {105-109}, doi = {10.1038/s41586-018-0553-9}, pmid = {30283103}, issn = {1476-4687}, abstract = {Quaternary amino acids, in which the α-carbon that bears the amino and carboxyl groups also carries two carbon substituents, have an important role as modifiers of peptide conformation and bioactivity and as precursors of medicinally important compounds1,2. In contrast to enantioselective alkylation at this α-carbon, for which there are several methods3-8, general enantioselective introduction of an aryl substituent at the α-carbon is synthetically challenging9. Nonetheless, the resultant α-aryl amino acids and their derivatives are valuable precursors to bioactive molecules10,11. Here we describe the synthesis of quaternary α-aryl amino acids from enantiopure amino acid precursors by α-arylation without loss of stereochemical integrity. Our approach relies on the temporary formation of a second stereogenic centre in an N'-arylurea adduct12 of an imidazolidinone derivative6 of the precursor amino acid, and uses readily available enantiopure amino acids both as a precursor and as a source of asymmetry. It avoids the use of valuable transition metals, and enables arylation with electron-rich, electron-poor and heterocyclic substituents. Either enantiomer of the product can be formed from a single amino acid precursor. The method is practical and scalable, and provides the opportunity to produce α-arylated quaternary amino acids in multi-gram quantities.}, } @article {pmid30283102, year = {2018}, author = {Liu, Y and Aziguli, H and Zhang, B and Xu, W and Lu, W and Bernholc, J and Wang, Q}, title = {Ferroelectric polymers exhibiting behaviour reminiscent of a morphotropic phase boundary.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {96-100}, doi = {10.1038/s41586-018-0550-z}, pmid = {30283102}, issn = {1476-4687}, abstract = {Piezoelectricity-the direct interconversion between mechanical and electrical energies-is usually remarkably enhanced at the morphotropic phase boundary of ferroelectric materials1-4, which marks a transition region in the phase diagram of piezoelectric materials and bridges two competing phases with distinct symmetries1,5. Such enhancement has enabled the recent development of various lead and lead-free piezoelectric perovskites with outstanding piezoelectric properties for use in actuators, transducers, sensors and energy-harvesting applications5-8. However, the morphotropic phase boundary has never been observed in organic materials, and the absence of effective approaches to improving the intrinsic piezoelectric responses of polymers9,10 considerably hampers their application to flexible, wearable and biocompatible devices. Here we report stereochemically induced behaviour in ferroelectric poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) copolymers, which is similar to that observed at morphotropic phase boundaries in perovskites. We reveal that compositionally tailored tacticity (the stereochemical arrangement of chiral centres related to the TrFE monomers11,12) can lead to intramolecular order-to-disorder evolution in the crystalline phase and thus to an intermediate transition region that is reminiscent of the morphotropic phase boundary, where competing ferroelectric and relaxor properties appear simultaneously. Our first-principles calculations confirm the crucial role of chain tacticity in driving the formation of this transition region via structural competition between the trans-planar and 3/1-helical phases. We show that the P(VDF-TrFE) copolymer with the morphotropic composition exhibits a longitudinal piezoelectric coefficient of -63.5 picocoulombs per newton, outperforming state-of-the-art piezoelectric polymers10. Given the flexibility in the molecular design and synthesis of organic ferroelectric materials, this work opens up the way for the development of scalable, high-performance piezoelectric polymers.}, } @article {pmid30283055, year = {2018}, author = {Elliott, AM and Friedman, JM}, title = {The importance of genetic counselling in genome-wide sequencing.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {735-736}, doi = {10.1038/s41576-018-0057-3}, pmid = {30283055}, issn = {1471-0064}, } @article {pmid30283054, year = {2018}, author = {Escalona, M and Rocha, S and Posada, D}, title = {Author Correction: A comparison of tools for the simulation of genomic next-generation sequencing data.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {733}, doi = {10.1038/s41576-018-0058-2}, pmid = {30283054}, issn = {1471-0064}, abstract = {The originally published article contained errors in Fig. 1 (Decision tree for the selection of a suitable NGS genomic simulator), whereby the labels 'Variants' and 'No Variants' had been switched. The correct figure is presented in this notice.}, } @article {pmid30282744, year = {2018}, author = {Hsu, PK and Takahashi, Y and Munemasa, S and Merilo, E and Laanemets, K and Waadt, R and Pater, D and Kollist, H and Schroeder, JI}, title = {Abscisic acid-independent stomatal CO2 signal transduction pathway and convergence of CO2 and ABA signaling downstream of OST1 kinase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9971-E9980}, pmid = {30282744}, issn = {1091-6490}, support = {P42 ES010337/ES/NIEHS NIH HHS/United States ; }, mesh = {Abscisic Acid/*pharmacology ; Arabidopsis/drug effects/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Carbon Dioxide/*pharmacology ; Gene Expression Regulation, Plant/*drug effects ; Mutation ; Plant Growth Regulators/pharmacology ; Plant Stomata/drug effects/growth & development/*metabolism ; Protein Kinases/genetics/*metabolism ; Reactive Oxygen Species/metabolism ; Signal Transduction/*drug effects ; }, abstract = {Stomatal pore apertures are narrowing globally due to the continuing rise in atmospheric [CO2]. CO2 elevation and the plant hormone abscisic acid (ABA) both induce rapid stomatal closure. However, the underlying signal transduction mechanisms for CO2/ABA interaction remain unclear. Two models have been considered: (i) CO2 elevation enhances ABA concentrations and/or early ABA signaling in guard cells to induce stomatal closure and (ii) CO2 signaling merges with ABA at OST1/SnRK2.6 protein kinase activation. Here we use genetics, ABA-reporter imaging, stomatal conductance, patch clamp, and biochemical analyses to investigate these models. The strong ABA biosynthesis mutants nced3/nced5 and aba2-1 remain responsive to CO2 elevation. Rapid CO2-triggered stomatal closure in PYR/RCAR ABA receptor quadruple and hextuple mutants is not disrupted but delayed. Time-resolved ABA concentration monitoring in guard cells using a FRET-based ABA-reporter, ABAleon2.15, and ABA reporter gene assays suggest that CO2 elevation does not trigger [ABA] increases in guard cells, in contrast to control ABA exposures. Moreover, CO2 activates guard cell S-type anion channels in nced3/nced5 and ABA receptor hextuple mutants. Unexpectedly, in-gel protein kinase assays show that unlike ABA, elevated CO2 does not activate OST1/SnRK2 kinases in guard cells. The present study points to a model in which rapid CO2 signal transduction leading to stomatal closure occurs via an ABA-independent pathway downstream of OST1/SnRK2.6. Basal ABA signaling and OST1/SnRK2 activity are required to facilitate the stomatal response to elevated CO2 These findings provide insights into the interaction between CO2/ABA signal transduction in light of the continuing rise in atmospheric [CO2].}, } @article {pmid30282743, year = {2018}, author = {Roussigné, M and Wei, L and Tsingos, E and Kuchling, F and Alkobtawi, M and Tsalavouta, M and Wittbrodt, J and Carl, M and Blader, P and Wilson, SW}, title = {Left/right asymmetric collective migration of parapineal cells is mediated by focal FGF signaling activity in leading cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9812-E9821}, pmid = {30282743}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Animals, Genetically Modified/physiology ; *Body Patterning ; *Cell Movement ; Embryo, Nonmammalian/cytology/*physiology ; Fibroblast Growth Factors/genetics/*metabolism ; *Functional Laterality ; Gene Expression Regulation, Developmental ; Pineal Gland/cytology/*physiology ; Signal Transduction ; Zebrafish/embryology/*physiology ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {The ability of cells to collectively interpret surrounding environmental signals underpins their capacity to coordinate their migration in various contexts, including embryonic development and cancer metastasis. One tractable model for studying collective migration is the parapineal, a left-sided group of neurons that arises from bilaterally positioned precursors that undergo a collective migration to the left side of the brain. In zebrafish, the migration of these cells requires Fgf8 and, in this study, we resolve how FGF signaling correlates with-and impacts the migratory dynamics of-the parapineal cell collective. The temporal and spatial dynamics of an FGF reporter transgene reveal that FGF signaling is activated in only few parapineal cells usually located at the leading edge of the parapineal during its migration. Overexpressing a constitutively active Fgf receptor compromises parapineal migration in wild-type embryos, while it partially restores both parapineal migration and mosaic expression of the FGF reporter transgene in fgf8-/- mutant embryos. Focal activation of FGF signaling in few parapineal cells is sufficient to promote the migration of the whole parapineal collective. Finally, we show that asymmetric Nodal signaling contributes to the restriction and leftwards bias of FGF pathway activation. Our data indicate that the first overt morphological asymmetry in the zebrafish brain is promoted by FGF pathway activation in cells that lead the collective migration of the parapineal to the left. This study shows that cell-state differences in FGF signaling in front versus rear cells is required to promote migration in a model of FGF-dependent collective migration.}, } @article {pmid30282742, year = {2018}, author = {Lin, LC and Qu, Y and Telzer, EH}, title = {Intergroup social influence on emotion processing in the brain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10630-10635}, pmid = {30282742}, issn = {1091-6490}, mesh = {Adult ; Brain/*physiology ; Brain Mapping ; Emotions/*physiology ; Female ; *Group Processes ; Humans ; Magnetic Resonance Imaging ; Male ; Neural Pathways/*physiology ; Prejudice ; *Social Behavior ; *Social Perception ; Theory of Mind/*physiology ; Young Adult ; }, abstract = {Emotions usually occur in a social context; yet little is known about how similar and dissimilar others influence our emotions. In the current study, we examined whether ingroup and outgroup members have differential influence on emotion processing at the behavioral and neural levels. To this end, we recruited 45 participants to rate a series of images displaying people engaged in different emotional contexts. Participants then underwent an fMRI scan where they viewed the same images along with information on how ingroup and outgroup members rated them, and they were asked to rate the images again. We found that participants shifted their emotions to be more in alignment with the ingroup over the outgroup, and that neural regions implicated in positive valuation [ventral striatum (VS) and ventromedial prefrontal cortex (vmPFC)], mentalizing [dorsomedial prefrontal cortex (dmPFC), medial prefrontal cortex (mPFC), posterior superior temporal sulcus (pSTS), and temporal pole], as well as emotion processing and salience detection (amygdala and insula), linearly tracked this behavior such that the extent of neural activity in these regions paralleled changes in participants' emotions. Results illustrate the powerful impact that ingroup members have on our emotions.}, } @article {pmid30282741, year = {2018}, author = {Grant, L and Langpap, C}, title = {Private provision of public goods by environmental groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1805336115}, pmid = {30282741}, issn = {1091-6490}, abstract = {Many environmental nonprofit groups are assumed to provide public goods. While an extensive literature examines why donors join and give to nonprofits, none directly tests whether donations actually provide public goods. We seek such a test by using a common form of environmental organization: watershed groups. We find their increased presence resulted in lower dissolved oxygen deficiency and higher proportions of swimmable and fishable water bodies. Increased donations to and expenditures by the groups also improved water quality. Thus, private groups likely played a role in mitigating environmental problems. Overall, our results indicate private provision of a public good by nonprofit organizations.}, } @article {pmid30282740, year = {2018}, author = {Raunsgard, A and Opedal, ØH and Ekrem, RK and Wright, J and Bolstad, GH and Armbruster, WS and Pélabon, C}, title = {Intersexual conflict over seed size is stronger in more outcrossed populations of a mixed-mating plant.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11561-11566}, pmid = {30282740}, issn = {1091-6490}, abstract = {In polyandrous species, fathers benefit from attracting greater maternal investment toward their offspring at the expense of the offspring of other males, while mothers should usually allocate resources equally among offspring. This conflict can lead to an evolutionary arms race between the sexes, manifested through antagonistic genes whose expression in offspring depends upon the parent of origin. The arms race may involve an increase in the strength of maternally versus paternally derived alleles engaged in a "tug of war" over maternal provisioning or repeated "recognition-avoidance" coevolution where growth-enhancing paternally derived alleles evolve to escape recognition by maternal genes targeted to suppress their effect. Here, we develop predictions to distinguish between these two mechanisms when considering crosses among populations that have reached different equilibria in this intersexual arms race. We test these predictions using crosses within and among populations of Dalechampia scandens (Euphorbiaceae) that presumably have experienced different intensities of intersexual conflict, as inferred from their historical differences in mating system. In crosses where the paternal population was more outcrossed than the maternal population, hybrid seeds were larger than those normally produced in the maternal population, whereas when the maternal population was more outcrossed, hybrid seeds were smaller than normal. These results confirm the importance of mating systems in determining the intensity of intersexual conflict over maternal investment and provide strong support for a tug-of-war mechanism operating in this conflict. They also yield clear predictions for the fitness consequences of gene flow among populations with different mating histories.}, } @article {pmid30282739, year = {2018}, author = {Li, H and Sosa-Calvo, J and Horn, HA and Pupo, MT and Clardy, J and Rabeling, C and Schultz, TR and Currie, CR}, title = {Convergent evolution of complex structures for ant-bacterial defensive symbiosis in fungus-farming ants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10720-10725}, pmid = {30282739}, issn = {1091-6490}, support = {U19 AI109673/AI/NIAID NIH HHS/United States ; U19 TW009872/TW/FIC NIH HHS/United States ; }, mesh = {Actinobacteria/*physiology ; Animals ; Ants/*microbiology ; *Biological Evolution ; Fungi/*physiology ; *Host-Pathogen Interactions ; Phylogeny ; *Symbiosis ; }, abstract = {Evolutionary adaptations for maintaining beneficial microbes are hallmarks of mutualistic evolution. Fungus-farming "attine" ant species have complex cuticular modifications and specialized glands that house and nourish antibiotic-producing Actinobacteria symbionts, which in turn protect their hosts' fungus gardens from pathogens. Here we reconstruct ant-Actinobacteria evolutionary history across the full range of variation within subtribe Attina by combining dated phylogenomic and ultramorphological analyses. Ancestral-state analyses indicate the ant-Actinobacteria symbiosis arose early in attine-ant evolution, a conclusion consistent with direct observations of Actinobacteria on fossil ants in Oligo-Miocene amber. qPCR indicates that the dominant ant-associated Actinobacteria belong to the genus Pseudonocardia Tracing the evolutionary trajectories of Pseudonocardia-maintaining mechanisms across attine ants reveals a continuum of adaptations. In Myrmicocrypta species, which retain many ancestral morphological and behavioral traits, Pseudonocardia occur in specific locations on the legs and antennae, unassociated with any specialized structures. In contrast, specialized cuticular structures, including crypts and tubercles, evolved at least three times in derived attine-ant lineages. Conspicuous caste differences in Pseudonocardia-maintaining structures, in which specialized structures are present in worker ants and queens but reduced or lost in males, are consistent with vertical Pseudonocardia transmission. Although the majority of attine ants are associated with Pseudonocardia, there have been multiple losses of bacterial symbionts and bacteria-maintaining structures in different lineages over evolutionary time. The early origin of ant-Pseudonocardia mutualism and the multiple evolutionary convergences on strikingly similar anatomical adaptations for maintaining bacterial symbionts indicate that Pseudonocardia have played a critical role in the evolution of ant fungiculture.}, } @article {pmid30282738, year = {2018}, author = {Maidenbaum, S and Miller, J and Stein, JM and Jacobs, J}, title = {Grid-like hexadirectional modulation of human entorhinal theta oscillations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10798-10803}, pmid = {30282738}, issn = {1091-6490}, support = {R01 MH061975/MH/NIMH NIH HHS/United States ; R01 MH104606/MH/NIMH NIH HHS/United States ; }, mesh = {Action Potentials ; Entorhinal Cortex/*physiology ; Grid Cells/*physiology ; Humans ; *Models, Neurological ; Neurons/*physiology ; Space Perception/*physiology ; Spatial Memory ; Spatial Navigation ; Theta Rhythm/*physiology ; }, abstract = {The entorhinal cortex contains a network of grid cells that play a fundamental part in the brain's spatial system, supporting tasks such as path integration and spatial memory. In rodents, grid cells are thought to rely on network theta oscillations, but such signals are not evident in all species, challenging our understanding of the physiological basis of the grid network. We analyzed intracranial recordings from neurosurgical patients during virtual navigation to identify oscillatory characteristics of the human entorhinal grid network. The power of entorhinal theta oscillations showed six-fold modulation according to the virtual heading during navigation, which is a hypothesized signature of grid representations. Furthermore, modulation strength correlated with spatial memory performance. These results demonstrate the connection between theta oscillations and the human entorhinal grid network and show that features of grid-like neuronal representations can be identified from population electrophysiological recordings.}, } @article {pmid30282737, year = {2018}, author = {Julien, JD and Alim, K}, title = {Oscillatory fluid flow drives scaling of contraction wave with system size.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10612-10617}, pmid = {30282737}, issn = {1091-6490}, mesh = {Actin Cytoskeleton/*metabolism ; Actomyosin/*metabolism ; Animals ; *Mechanotransduction, Cellular ; *Models, Biological ; *Models, Theoretical ; Muscle Contraction/*physiology ; }, abstract = {Flows over remarkably long distances are crucial to the functioning of many organisms, across all kingdoms of life. Coordinated flows are fundamental to power deformations, required for migration or development, or to spread resources and signals. A ubiquitous mechanism to generate flows, particularly prominent in animals and amoebas, is actomyosin cortex-driven mechanical deformations that pump the fluid enclosed by the cortex. However, it is unclear how cortex dynamics can self-organize to give rise to coordinated flows across the largely varying scales of biological systems. Here, we develop a mechanochemical model of actomyosin cortex mechanics coupled to a contraction-triggering, soluble chemical. The chemical itself is advected with the flows generated by the cortex-driven deformations of the tubular-shaped cell. The theoretical model predicts a dynamic instability giving rise to stable patterns of cortex contraction waves and oscillatory flows. Surprisingly, simulated patterns extend beyond the intrinsic length scale of the dynamic instability-scaling with system size instead. Patterns appear randomly but can be robustly generated in a growing system or by flow-generating boundary conditions. We identify oscillatory flows as the key for the scaling of contraction waves with system size. Our work shows the importance of active flows in biophysical models of patterning, not only as a regulating input or an emergent output, but also as a full part of a self-organized machinery. Contractions and fluid flows are observed in all kinds of organisms, so this concept is likely to be relevant for a broad class of systems.}, } @article {pmid30282736, year = {2018}, author = {Tan, S and Xiao, Y and Yin, HH and Chen, AI and Soong, TW and Je, HS}, title = {Postnatal TrkB ablation in corticolimbic interneurons induces social dominance in male mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9909-E9915}, pmid = {30282736}, issn = {1091-6490}, support = {R01 MH112883/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Behavior, Animal ; Brain-Derived Neurotrophic Factor/genetics/*metabolism ; Cerebral Cortex/cytology/*physiology ; GABAergic Neurons/cytology/*physiology ; Interneurons/cytology/*physiology ; Limbic System/cytology/*physiology ; Male ; Membrane Glycoproteins/*physiology ; Mice ; Mice, Knockout ; Mice, Transgenic ; Prefrontal Cortex/cytology/physiology ; Protein-Tyrosine Kinases/*physiology ; Signal Transduction ; *Social Dominance ; }, abstract = {The tight balance between synaptic excitation and inhibition (E/I) within neocortical circuits in the mammalian brain is important for complex behavior. Many loss-of-function studies have demonstrated that brain-derived neurotrophic factor (BDNF) and its cognate receptor tropomyosin receptor kinase B (TrkB) are essential for the development of inhibitory GABAergic neurons. However, behavioral consequences of impaired BDNF/TrkB signaling in GABAergic neurons remain unclear, largely due to confounding motor function deficits observed in previous animal models. In this study, we generated conditional knockout mice (TrkB cKO) in which TrkB was ablated from a majority of corticolimbic GABAergic interneurons postnatally. These mice showed intact motor coordination and movement, but exhibited enhanced dominance over other mice in a group-housed setting. In addition, immature fast-spiking GABAergic neurons of TrkB cKO mice resulted in an E/I imbalance in layer 5 microcircuits within the medial prefrontal cortex (mPFC), a key region regulating social dominance. Restoring the E/I imbalance via optogenetic modulation in the mPFC of TrkB cKO mice normalized their social dominance behavior. Taken together, our results provide strong evidence for a role of BDNF/TrkB signaling in inhibitory synaptic modulation and social dominance behavior in mice.}, } @article {pmid30282735, year = {2018}, author = {Janes, J and Young, ME and Chen, E and Rogers, NH and Burgstaller-Muehlbacher, S and Hughes, LD and Love, MS and Hull, MV and Kuhen, KL and Woods, AK and Joseph, SB and Petrassi, HM and McNamara, CW and Tremblay, MS and Su, AI and Schultz, PG and Chatterjee, AK}, title = {The ReFRAME library as a comprehensive drug repurposing library and its application to the treatment of cryptosporidiosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10750-10755}, pmid = {30282735}, issn = {1091-6490}, support = {R01 GM089820/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antiprotozoal Agents/*pharmacology ; Cryptosporidiosis/*drug therapy/parasitology ; Cryptosporidium/*drug effects ; *Databases, Pharmaceutical ; *Drug Discovery ; Drug Evaluation, Preclinical/methods ; Drug Repositioning/*methods ; Female ; High-Throughput Screening Assays ; Humans ; Mice ; Mice, Inbred C57BL ; Small Molecule Libraries/*pharmacology ; }, abstract = {The chemical diversity and known safety profiles of drugs previously tested in humans make them a valuable set of compounds to explore potential therapeutic utility in indications outside those originally targeted, especially neglected tropical diseases. This practice of "drug repurposing" has become commonplace in academic and other nonprofit drug-discovery efforts, with the appeal that significantly less time and resources are required to advance a candidate into the clinic. Here, we report a comprehensive open-access, drug repositioning screening set of 12,000 compounds (termed ReFRAME; Repurposing, Focused Rescue, and Accelerated Medchem) that was assembled by combining three widely used commercial drug competitive intelligence databases (Clarivate Integrity, GVK Excelra GoStar, and Citeline Pharmaprojects), together with extensive patent mining of small molecules that have been dosed in humans. To date, 12,000 compounds (∼80% of compounds identified from data mining) have been purchased or synthesized and subsequently plated for screening. To exemplify its utility, this collection was screened against Cryptosporidium spp., a major cause of childhood diarrhea in the developing world, and two active compounds previously tested in humans for other therapeutic indications were identified. Both compounds, VB-201 and a structurally related analog of ASP-7962, were subsequently shown to be efficacious in animal models of Cryptosporidium infection at clinically relevant doses, based on available human doses. In addition, an open-access data portal (https://reframedb.org) has been developed to share ReFRAME screen hits to encourage additional follow-up and maximize the impact of the ReFRAME screening collection.}, } @article {pmid30282734, year = {2018}, author = {Lin, W and Su, F and Gautam, R and Wang, N and Zhang, Y and Wang, X}, title = {Raf kinase inhibitor protein negatively regulates FcεRI-mediated mast cell activation and allergic response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9859-E9868}, pmid = {30282734}, issn = {1091-6490}, mesh = {Anaphylaxis/*immunology/metabolism ; Animals ; Asthma/*immunology/metabolism ; Cell Degranulation ; Cells, Cultured ; Child ; Humans ; Mast Cells/*immunology/metabolism ; Mice ; Mice, Knockout ; Phosphatidylethanolamine Binding Protein/*physiology ; Receptors, IgE/*metabolism ; Signal Transduction ; }, abstract = {The signaling cascades triggered by the cross-linkage of immunoglobulin E (IgE) with its high-affinity receptor (FcεRI) on mast cells contribute to multiple allergic disorders, such as asthma, rhinitis, and atopic dermatitis. Restraint of intracellular signals for mast cell activation is essential to restore homeostasis. In this study, we found that Raf kinase inhibitor protein (RKIP) negatively regulated mast cell activation. RKIP-deficient mast cells showed greater IgE-FcεRI-mediated activation than wild-type mast cells. Consistently, RKIP deficiency in mast cells rendered mice more sensitive to IgE-FcεRI-mediated allergic responses and ovalbumin-induced airway inflammation. Mechanistically, RKIP interacts with the p85 subunit of PI3K, prevents it from binding to GRB2-associated binding protein 2 (Gab2), and eventually inhibits the activation of the PI3K/Akt/NF-κB complex and its downstream signaling. Furthermore, the expression of RKIP was significantly down-regulated in the peripheral blood of asthma patients and in the IgE-FcεRI-stimulated mast cells. Collectively, our findings not only suggest that RKIP plays an important role in controlling mast cell-mediated allergic responses but also provide insight into therapeutic targets for mast cell-related allergic diseases.}, } @article {pmid30282733, year = {2018}, author = {Leahy, IA and Lin, YP and Siegfried, PE and Treglia, AC and Song, JCW and Nandkishore, RM and Lee, M}, title = {Nonsaturating large magnetoresistance in semimetals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10570-10575}, pmid = {30282733}, issn = {1091-6490}, abstract = {The rapidly expanding class of quantum materials known as topological semimetals (TSMs) displays unique transport properties, including a striking dependence of resistivity on applied magnetic field, that are of great interest for both scientific and technological reasons. So far, many possible sources of extraordinarily large nonsaturating magnetoresistance have been proposed. However, experimental signatures that can identify or discern the dominant mechanism and connect to available theories are scarce. Here we present the magnetic susceptibility (χ), the tangent of the Hall angle ([Formula: see text]), along with magnetoresistance in four different nonmagnetic semimetals with high mobilities, NbP, TaP, NbSb2, and TaSb2, all of which exhibit nonsaturating large magnetoresistance (MR). We find that the distinctly different temperature dependences, [Formula: see text], and the values of [Formula: see text] in phosphides and antimonates serve as empirical criteria to sort the MR from different origins: NbP and TaP are uncompensated semimetals with linear dispersion, in which the nonsaturating magnetoresistance arises due to guiding center motion, while NbSb2 and TaSb2 are compensated semimetals, with a magnetoresistance emerging from nearly perfect charge compensation of two quadratic bands. Our results illustrate how a combination of magnetotransport and susceptibility measurements may be used to categorize the increasingly ubiquitous nonsaturating large magnetoresistance in TSMs.}, } @article {pmid30282470, year = {2018}, author = {Lehmann, GK and Elliot, AJ and Calin-Jageman, RJ}, title = {Meta-Analysis of the Effect of Red on Perceived Attractiveness.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {4}, pages = {1474704918802412}, doi = {10.1177/1474704918802412}, pmid = {30282470}, issn = {1474-7049}, abstract = {We conducted meta-analyses of studies that test the red-romance hypothesis, which is that the color red enhances heterosexual attraction in romantic contexts. For men rating women, we found a small, statistically significant effect (d = 0.26 [0.12, 0.40], p = .0004, N = 2,961), with substantial heterogeneity, Q(44) = 172.5, pQ < .0001, I2 = 89% [82, 94], and equivocal results regarding the possibility of upward bias in the estimate. For women rating men, we found a very small effect (d = 0.13 [0.01, 0.25], p = .03, N = 2,739), with substantial heterogeneity, Q(35) = 73.0, pQ = .0002, I2 = 53% [33, 80], and evidence of upward bias in the estimate. Moderator analyses suggest effect sizes may have declined over time (both genders), may be largest when an original shade of red is used (men only), and may be smaller in preregistered studies (women only). We present contrasting interpretations and suggestions for future research.}, } @article {pmid30281016, year = {2018}, author = {Maki, JJ and Looft, T}, title = {Megasphaera stantonii sp. nov., a butyrate-producing bacterium isolated from the cecum of a healthy chicken.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3409-3415}, doi = {10.1099/ijsem.0.002991}, pmid = {30281016}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Cecum/*microbiology ; Chickens/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Megasphaera/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A novel mesophilic, anaerobic, Gram-stain-negative bacterium was isolated from the cecum of a healthy white leghorn chicken, and designated AJH120T. Cells were coccoid or diplococcoid with an average size of 0.8-1.8 µm and were non-motile with no evidence of spores. Phylogenetic analysis of 16S rRNA gene sequences revealed this organism to be a member of the genus Megasphaera, with the closest relatives being Megasphaera elsdenii (95 % sequence identity) and Megasphaera cerevisiae (95 % sequence identity). Growth was observed between 30 and 50 °C and between pH 5.0 and 9.0. AJH120T utilized a variety of carbon sources, including succinate, gluconate, fructose, ribose and pyruvate, as well as many individual amino acids. The DNA G+C content for the genome sequence of AJH120T was 52.1 mol%. Digital DNA-DNA hybridization (dDDH), average nucleotide identity (ANI) and average amino acid identity (AAI) between AJH120T and close taxonomic relatives, indicated divergence consistent with the strain representing a novel species. The major fatty acid methyl esters of the organism were C12 : 0, C14 : 0 3-OH, C18 : 1ω9c, C16 : 0 and C16 : 1ω9c. AJH120T was able to produce several short chain fatty acids, including butyrate, acetate, propionate and isovalerate. Together, these data indicate that AJH120T represents a novel species within the genus Megasphaera. We propose the name Megasphaerastantonii sp. nov. for the species. The type strain of this species is AJH120T (=DSM 106750T=CCUG 71842T).}, } @article {pmid30281015, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 7, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3077-3079}, doi = {10.1099/ijsem.0.002901}, pmid = {30281015}, issn = {1466-5034}, } @article {pmid30280505, year = {2018}, author = {Kwak, HJ and Ryu, KB and Medina Jiménez, BI and Park, SC and Cho, SJ}, title = {Temporal and spatial expression of the Fox gene family in the Leech Helobdella austinensis.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {6-7}, pages = {341-350}, doi = {10.1002/jez.b.22828}, pmid = {30280505}, issn = {1552-5015}, support = {PJ011661//Cooperative Research Program for Agriculture Science & Technology Development/ ; NIBR201839201//National Institute of Biological Resources/ ; }, abstract = {The Forkhead box (Fox) gene family is an evolutionarily ancient gene family named after the Drosophila melanogaster forkhead gene (fkh). Fox genes are highly conserved transcription factors critical for embryogenesis and carcinogenesis. In the current study, we report a whole-genome survey of Fox genes and their expression patterns in the leech Helobdella austienesis. Phylogenetic analysis suggests that some Fox genes of leeches are correlated with other Lophotrochozoa and vertebrate Fox genes. Here we have performed semiquantitative reverse transcription polymerase chain reaction and whole-mount in situ hybridization of Fox genes throughout the embryonic development of H. austinensis. We found that each one of the leech Fox genes (FoxA1, FoxA3, FoxC, FoxL2, FoxO1, and FoxO2) is expressed in a specific set of cells or tissue type. From Stages 9-11, Hau-FoxA1 was expressed in the foregut of the anterior region, and Hau-FoxL2 was expressed in mesodermal muscle fiber. Hau-FoxA3 was temporally expressed in the ventral neuroectoderm. At Stage 11, Hau-FoxC was expressed in the foregut. Hau-FoxO genes have a ubiquitous expression. Our results provide more insight on the evolutionary linkage and role of the Fox gene function in Bilateria.}, } @article {pmid30280477, year = {2018}, author = {Bolam, FC and Grainger, MJ and Mengersen, KL and Stewart, GB and Sutherland, WJ and Runge, MC and McGowan, PJK}, title = {Using the Value of Information to improve conservation decision making.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12471}, pmid = {30280477}, issn = {1469-185X}, abstract = {Conservation decisions are challenging, not only because they often involve difficult conflicts among outcomes that people value, but because our understanding of the natural world and our effects on it is fraught with uncertainty. Value of Information (VoI) methods provide an approach for understanding and managing uncertainty from the standpoint of the decision maker. These methods are commonly used in other fields (e.g. economics, public health) and are increasingly used in biodiversity conservation. This decision-analytical approach can identify the best management alternative to select where the effectiveness of interventions is uncertain, and can help to decide when to act and when to delay action until after further research. We review the use of VoI in the environmental domain, reflect on the need for greater uptake of VoI, particularly for strategic conservation planning, and suggest promising areas for new research. We also suggest common reporting standards as a means of increasing the leverage of this powerful tool. The environmental science, ecology and biodiversity categories of the Web of Knowledge were searched using the terms 'Value of Information,' 'Expected Value of Perfect Information,' and the abbreviation 'EVPI.' Google Scholar was searched with the same terms, and additionally the terms decision and biology, biodiversity conservation, fish, or ecology. We identified 1225 papers from these searches. Included studies were limited to those that showed an application of VoI in biodiversity conservation rather than simply describing the method. All examples of use of VOI were summarised regarding the application of VoI, the management objectives, the uncertainties, the models used, how the objectives were measured, and the type of VoI. While the use of VoI appears to be on the increase in biodiversity conservation, the reporting of results is highly variable, which can make it difficult to understand the decision context and which uncertainties were considered. Moreover, it was unclear if, and how, the papers informed management and policy interventions, which is why we suggest a range of reporting standards that would aid the use of VoI. The use of VoI in conservation settings is at an early stage. There are opportunities for broader applications, not only for species-focussed management problems, but also for setting local or global research priorities for biodiversity conservation, making funding decisions, or designing or improving protected area networks and management. The long-term benefits of applying VoI methods to biodiversity conservation include a more structured and decision-focused allocation of resources to research.}, } @article {pmid30279605, year = {2018}, author = {}, title = {Super-tomato shows what plant scientists can do.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {8}, doi = {10.1038/d41586-018-06915-y}, pmid = {30279605}, issn = {1476-4687}, mesh = {Chromosome Mapping ; Gene Expression Regulation, Plant ; *Genome, Plant ; Lycopersicon esculentum/*genetics ; Plant Diseases ; Plant Leaves ; Plant Proteins/genetics ; }, } @article {pmid30279604, year = {2018}, author = {Cyranoski, D}, title = {China to train African scientists as part of $60-billion development plan.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {15-16}, doi = {10.1038/d41586-018-06722-5}, pmid = {30279604}, issn = {1476-4687}, mesh = {Africa ; Agriculture/economics/*education/methods ; China ; Commerce ; Congresses as Topic/economics/organization & administration ; Developing Countries/economics ; *Diplomacy ; Fellowships and Scholarships ; Investments ; Research/economics/*education/organization & administration ; Research Personnel/economics/*education ; Workforce ; }, } @article {pmid30279603, year = {2018}, author = {Fraser, B}, title = {Peru's oldest and largest Amazonian oil field poised for clean up.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {18-19}, doi = {10.1038/d41586-018-06886-0}, pmid = {30279603}, issn = {1476-4687}, mesh = {Animals ; Environmental Pollution/*prevention & control/*statistics & numerical data ; *Environmental Restoration and Remediation/trends ; *Oil and Gas Fields ; Peru ; }, } @article {pmid30279602, year = {2018}, author = {Castelvecchi, D and Gibney, E and Warren, M}, title = {Physics Nobel won by laser wizardry - laureates include first woman in 55 years.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {20}, doi = {10.1038/d41586-018-06752-z}, pmid = {30279602}, issn = {1476-4687}, mesh = {History, 20th Century ; History, 21st Century ; *Lasers/history ; *Nobel Prize ; *Optical Tweezers/history ; Physics/history/*standards ; Sex Factors ; Sexism/history/*statistics & numerical data ; }, } @article {pmid30279601, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {48}, doi = {10.1038/d41586-018-06866-4}, pmid = {30279601}, issn = {1476-4687}, } @article {pmid30279600, year = {2018}, author = {Ledford, H and Else, H and Warren, M}, title = {Cancer immunologists scoop medicine Nobel prize.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {20-21}, doi = {10.1038/d41586-018-06751-0}, pmid = {30279600}, issn = {1476-4687}, mesh = {Allergy and Immunology/history/*standards ; Animals ; CTLA-4 Antigen/antagonists & inhibitors/immunology ; History, 20th Century ; History, 21st Century ; Humans ; *Immunotherapy/history ; Ipilimumab/immunology/therapeutic use ; Japan ; Medicine/*standards ; Mice ; Neoplasms/*immunology/pathology/*therapy ; *Nobel Prize ; Programmed Cell Death 1 Receptor/antagonists & inhibitors/immunology ; United States ; }, } @article {pmid30279599, year = {2018}, author = {Matthews, D}, title = {Supercharge your data wrangling with a graphics card.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {151-152}, doi = {10.1038/d41586-018-06870-8}, pmid = {30279599}, issn = {1476-4687}, } @article {pmid30279598, year = {2018}, author = {}, title = {Degree completion linked to peer support.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {155}, doi = {10.1038/d41586-018-06872-6}, pmid = {30279598}, issn = {1476-4687}, } @article {pmid30279596, year = {2018}, author = {Gibney, E}, title = {What the Nobels are - and aren't - doing to encourage diversity.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {19}, doi = {10.1038/d41586-018-06879-z}, pmid = {30279596}, issn = {1476-4687}, mesh = {History, 20th Century ; History, 21st Century ; *Nobel Prize ; Sex Factors ; Sexism/history/*prevention & control/*statistics & numerical data/trends ; Stereotyping ; }, } @article {pmid30279595, year = {2018}, author = {Wild, S}, title = {South Africa's largest dinosaur upends theories of how four-legged walking began.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {17}, doi = {10.1038/d41586-018-06881-5}, pmid = {30279595}, issn = {1476-4687}, mesh = {Animals ; *Dinosaurs ; South Africa ; *Walking ; }, } @article {pmid30279594, year = {2018}, author = {Woolston, C}, title = {Why Canada's immigration regulations may be pushing postdocs out.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {155}, doi = {10.1038/d41586-018-06852-w}, pmid = {30279594}, issn = {1476-4687}, } @article {pmid30279593, year = {2018}, author = {Reardon, S}, title = {Trump administration launches sweeping review of fetal-tissue research.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {16-17}, doi = {10.1038/d41586-018-06841-z}, pmid = {30279593}, issn = {1476-4687}, mesh = {Animals ; Fetal Research/ethics/*legislation & jurisprudence ; Humans ; Mice ; National Institutes of Health (U.S.)/legislation & jurisprudence ; United States ; United States Dept. of Health and Human Services/*legislation & jurisprudence ; United States Food and Drug Administration/legislation & jurisprudence ; }, } @article {pmid30279576, year = {2018}, author = {Munschauer, M and Nguyen, CT and Sirokman, K and Hartigan, CR and Hogstrom, L and Engreitz, JM and Ulirsch, JC and Fulco, CP and Subramanian, V and Chen, J and Schenone, M and Guttman, M and Carr, SA and Lander, ES}, title = {Publisher Correction: The NORAD lncRNA assembles a topoisomerase complex critical for genome stability.}, journal = {Nature}, volume = {563}, number = {7733}, pages = {E32}, doi = {10.1038/s41586-018-0584-2}, pmid = {30279576}, issn = {1476-4687}, abstract = {A typo in the 'Reviewer information' section of this Letter was corrected online.}, } @article {pmid30279525, year = {2018}, author = {Trenkmann, M}, title = {Putting genetic variants to a fitness test.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {667}, doi = {10.1038/s41576-018-0056-4}, pmid = {30279525}, issn = {1471-0064}, } @article {pmid30279240, year = {2018}, author = {Shen, HH}, title = {Core Concept: Perineuronal nets gain prominence for their role in learning, memory, and plasticity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9813-9815}, pmid = {30279240}, issn = {1091-6490}, mesh = {Animals ; Humans ; Learning/*physiology ; Memory/*physiology ; Nerve Net/cytology/*physiology ; Neuronal Plasticity/*physiology ; }, } @article {pmid30279239, year = {2018}, author = {Ananthaswamy, A}, title = {Inner Workings: How fast is the universe expanding? Clashing measurements may point to new physics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9810-9812}, pmid = {30279239}, issn = {1091-6490}, } @article {pmid30279184, year = {2018}, author = {Rybicki, J and Kisdi, E and Anttila, JV}, title = {Model of bacterial toxin-dependent pathogenesis explains infective dose.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10690-10695}, pmid = {30279184}, issn = {1091-6490}, mesh = {Bacteria/*pathogenicity ; Bacterial Infections/*microbiology ; Bacterial Toxins/*administration & dosage/pharmacology ; Humans ; *Models, Theoretical ; *Virulence ; Virulence Factors/*administration & dosage/pharmacology ; }, abstract = {The initial amount of pathogens required to start an infection within a susceptible host is called the infective dose and is known to vary to a large extent between different pathogen species. We investigate the hypothesis that the differences in infective doses are explained by the mode of action in the underlying mechanism of pathogenesis: Pathogens with locally acting mechanisms tend to have smaller infective doses than pathogens with distantly acting mechanisms. While empirical evidence tends to support the hypothesis, a formal theoretical explanation has been lacking. We give simple analytical models to gain insight into this phenomenon and also investigate a stochastic, spatially explicit, mechanistic within-host model for toxin-dependent bacterial infections. The model shows that pathogens secreting locally acting toxins have smaller infective doses than pathogens secreting diffusive toxins, as hypothesized. While local pathogenetic mechanisms require smaller infective doses, pathogens with distantly acting toxins tend to spread faster and may cause more damage to the host. The proposed model can serve as a basis for the spatially explicit analysis of various virulence factors also in the context of other problems in infection dynamics.}, } @article {pmid30279183, year = {2018}, author = {Balcells, L and Torrats-Espinosa, G}, title = {Using a natural experiment to estimate the electoral consequences of terrorist attacks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10624-10629}, pmid = {30279183}, issn = {1091-6490}, mesh = {*Choice Behavior ; *Democracy ; Humans ; *Politics ; *Public Policy ; Spain ; Surveys and Questionnaires ; Terrorism/*psychology ; }, abstract = {This study investigates the consequences of terrorist attacks for political behavior by leveraging a natural experiment in Spain. We study eight attacks against civilians, members of the military, and police officers perpetrated between 1989 and 1997 by Euskadi Ta Askatasuna (ETA), a Basque terrorist organization that was active between 1958 and 2011. We use nationally and regionally representative surveys that were being fielded when the attacks occurred to estimate the causal effect of terrorist violence on individuals' intent to participate in democratic elections as well as on professed support for the incumbent party. We find that both lethal and nonlethal terrorist attacks significantly increase individuals' intent to participate in a future democratic election. The magnitude of this impact is larger when attacks are directed against civilians than when directed against members of the military or the police. We find no evidence that the attacks change support for the incumbent party. These results suggest that terrorist attacks enhance political engagement of citizens.}, } @article {pmid30279182, year = {2018}, author = {Li, Y and Fu, TM and Lu, A and Witt, K and Ruan, J and Shen, C and Wu, H}, title = {Cryo-EM structures of ASC and NLRC4 CARD filaments reveal a unified mechanism of nucleation and activation of caspase-1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {10845-10852}, pmid = {30279182}, issn = {1091-6490}, support = {DP1 HD087988/HD/NICHD NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 AI124491/AI/NIAID NIH HHS/United States ; }, mesh = {CARD Signaling Adaptor Proteins/*chemistry/genetics/metabolism ; Calcium-Binding Proteins/*chemistry/genetics/metabolism ; Caspase 1/*chemistry/genetics/metabolism ; *Cryoelectron Microscopy ; Enzyme Activation ; Humans ; Inflammasomes ; *Models, Molecular ; Multiprotein Complexes/*chemistry/genetics/metabolism/*ultrastructure ; }, abstract = {Canonical inflammasomes are cytosolic supramolecular complexes that activate caspase-1 upon sensing extrinsic microbial invasions and intrinsic sterile stress signals. During inflammasome assembly, adaptor proteins ASC and NLRC4 recruit caspase-1 through homotypic caspase recruitment domain (CARD) interactions, leading to caspase-1 dimerization and activation. Activated caspase-1 processes proinflammatory cytokines and Gasdermin D to induce cytokine maturation and pyroptotic cell death. Here, we present cryo-electron microscopy (cryo-EM) structures of NLRC4 CARD and ASC CARD filaments mediated by conserved three types of asymmetric interactions (types I, II, and III). We find that the CARDs of these two adaptor proteins share a similar assembly pattern, which matches that of the caspase-1 CARD filament whose structure we defined previously. These data indicate a unified mechanism for downstream caspase-1 recruitment through CARD-CARD interactions by both adaptors. Using structure modeling, we further show that full-length NLRC4 assembles via two separate symmetries at its CARD and its nucleotide-binding domain (NBD), respectively.}, } @article {pmid30279181, year = {2018}, author = {Jin, JJ and Lv, W and Xia, P and Xu, ZY and Zheng, AD and Wang, XJ and Wang, SS and Zeng, R and Luo, HM and Li, GL and Zuo, B}, title = {Long noncoding RNA SYISL regulates myogenesis by interacting with polycomb repressive complex 2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9802-E9811}, pmid = {30279181}, issn = {1091-6490}, mesh = {Animals ; CRISPR-Cas Systems ; Cell Differentiation ; *Epigenesis, Genetic ; Gene Silencing ; Mice ; Mice, Knockout ; Muscle Development/*physiology ; Polycomb Repressive Complex 2/genetics/*metabolism ; Promoter Regions, Genetic ; RNA, Long Noncoding/genetics/*metabolism ; }, abstract = {Although many long noncoding RNAs (lncRNAs) have been identified in muscle, their physiological function and regulatory mechanisms remain largely unexplored. In this study, we systematically characterized the expression profiles of lncRNAs during C2C12 myoblast differentiation and identified an intronic lncRNA, SYISL (SYNPO2 intron sense-overlapping lncRNA), that is highly expressed in muscle. Functionally, SYISL promotes myoblast proliferation and fusion but inhibits myogenic differentiation. SYISL knockout in mice results in significantly increased muscle fiber density and muscle mass. Mechanistically, SYISL recruits the enhancer of zeste homolog 2 (EZH2) protein, the core component of polycomb repressive complex 2 (PRC2), to the promoters of the cell-cycle inhibitor gene p21 and muscle-specific genes such as myogenin (MyoG), muscle creatine kinase (MCK), and myosin heavy chain 4 (Myh4), leading to H3K27 trimethylation and epigenetic silencing of target genes. Taken together, our results reveal that SYISL is a repressor of muscle development and plays a vital role in PRC2-mediated myogenesis.}, } @article {pmid30279180, year = {2018}, author = {Murray, DT and Zhou, X and Kato, M and Xiang, S and Tycko, R and McKnight, SL}, title = {Structural characterization of the D290V mutation site in hnRNPA2 low-complexity-domain polymers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9782-E9791}, pmid = {30279180}, issn = {1091-6490}, support = {U01 GM107623/GM/NIGMS NIH HHS/United States ; FI2 GM117604/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Aspartic Acid/*chemistry/genetics ; Heterogeneous-Nuclear Ribonucleoprotein Group A-B/*chemistry/*genetics ; Humans ; Mutagenesis, Site-Directed ; *Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Polymers/*chemistry ; Protein Conformation ; Protein Domains ; }, abstract = {Human genetic studies have given evidence of familial, disease-causing mutations in the analogous amino acid residue shared by three related RNA binding proteins causative of three neurological diseases. Alteration of aspartic acid residue 290 of hnRNPA2 to valine is believed to predispose patients to multisystem proteinopathy. Mutation of aspartic acid 262 of hnRNPA1 to either valine or asparagine has been linked to either amyotrophic lateral sclerosis or multisystem proteinopathy. Mutation of aspartic acid 378 of hnRNPDL to either asparagine or histidine has been associated with limb girdle muscular dystrophy. All three of these aspartic acid residues map to evolutionarily conserved regions of low-complexity (LC) sequence that may function in states of either intrinsic disorder or labile self-association. Here, we present a combination of solid-state NMR spectroscopy with segmental isotope labeling and electron microscopy on the LC domain of the hnRNPA2 protein. We show that, for both the wild-type protein and the aspartic acid 290-to-valine mutant, labile polymers are formed in which the LC domain associates into an in-register cross-β conformation. Aspartic acid 290 is shown to be charged at physiological pH and immobilized within the polymer core. Polymers of the aspartic acid 290-to-valine mutant are thermodynamically more stable than wild-type polymers. These observations give evidence that removal of destabilizing electrostatic interactions may be responsible for the increased propensity of the mutated LC domains to self-associate in disease-causing conformations.}, } @article {pmid30279179, year = {2018}, author = {Barcellos, SH and Carvalho, LS and Turley, P}, title = {Education can reduce health differences related to genetic risk of obesity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9765-E9772}, pmid = {30279179}, issn = {1091-6490}, support = {P30 AG024962/AG/NIA NIH HHS/United States ; RF1 AG055654/AG/NIA NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; R01 AG042568/AG/NIA NIH HHS/United States ; K01 AG050811/AG/NIA NIH HHS/United States ; }, mesh = {Adolescent ; *Body Mass Index ; Body Size ; Child ; Child, Preschool ; *Educational Status ; Genetic Predisposition to Disease ; Humans ; Infant ; Infant, Newborn ; *Multifactorial Inheritance ; Obesity/epidemiology/genetics/*prevention & control ; Risk Factors ; Social Determinants of Health ; }, abstract = {This work investigates whether genetic makeup moderates the effects of education on health. Low statistical power and endogenous measures of environment have been obstacles to the credible estimation of such gene-by-environment interactions. We overcome these obstacles by combining a natural experiment that generated variation in secondary education with polygenic scores for a quarter-million individuals. The additional schooling affected body size, lung function, and blood pressure in middle age. The improvements in body size and lung function were larger for individuals with high genetic predisposition to obesity. As a result, education reduced the gap in unhealthy body size between those in the top and bottom terciles of genetic risk of obesity from 20 to 6 percentage points.}, } @article {pmid30279178, year = {2018}, author = {Ajoy, A and Nazaryan, R and Liu, K and Lv, X and Safvati, B and Wang, G and Druga, E and Reimer, JA and Suter, D and Ramanathan, C and Meriles, CA and Pines, A}, title = {Enhanced dynamic nuclear polarization via swept microwave frequency combs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10576-10581}, pmid = {30279178}, issn = {1091-6490}, abstract = {Dynamic nuclear polarization (DNP) has enabled enormous gains in magnetic resonance signals and led to vastly accelerated NMR/MRI imaging and spectroscopy. Unlike conventional cw-techniques, DNP methods that exploit the full electron spectrum are appealing since they allow direct participation of all electrons in the hyperpolarization process. Such methods typically entail sweeps of microwave radiation over the broad electron linewidth to excite DNP but are often inefficient because the sweeps, constrained by adiabaticity requirements, are slow. In this paper, we develop a technique to overcome the DNP bottlenecks set by the slow sweeps, using a swept microwave frequency comb that increases the effective number of polarization transfer events while respecting adiabaticity constraints. This allows a multiplicative gain in DNP enhancement, scaling with the number of comb frequencies and limited only by the hyperfine-mediated electron linewidth. We demonstrate the technique for the optical hyperpolarization of 13C nuclei in powdered microdiamonds at low fields, increasing the DNP enhancement from 30 to 100 measured with respect to the thermal signal at 7T. For low concentrations of broad linewidth electron radicals [e.g., TEMPO ((2,2,6,6-tetramethylpiperidin-1-yl)oxyl)], these multiplicative gains could exceed an order of magnitude.}, } @article {pmid30279177, year = {2018}, author = {Krishnan, S and Prise, IE and Wemyss, K and Schenck, LP and Bridgeman, HM and McClure, FA and Zangerle-Murray, T and O'Boyle, C and Barbera, TA and Mahmood, F and Bowdish, DME and Zaiss, DMW and Grainger, JR and Konkel, JE}, title = {Amphiregulin-producing γδ T cells are vital for safeguarding oral barrier immune homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10738-10743}, pmid = {30279177}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; BB/M025977/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 097820/Z/11/B//Wellcome Trust/United Kingdom ; }, mesh = {Amphiregulin/*metabolism ; Animals ; *Homeostasis ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mouth/*immunology/metabolism ; Periodontitis/*immunology/metabolism/pathology ; Receptors, Antigen, T-Cell, gamma-delta/*physiology ; T-Lymphocyte Subsets/*immunology/metabolism ; }, abstract = {γδ T cells are enriched at barrier sites such as the gut, skin, and lung, where their roles in maintaining barrier integrity are well established. However, how these cells contribute to homeostasis at the gingiva, a key oral barrier and site of the common chronic inflammatory disease periodontitis, has not been explored. Here we demonstrate that the gingiva is policed by γδ T cells with a T cell receptor (TCR) repertoire that diversifies during development. Gingival γδ T cells accumulated rapidly after birth in response to barrier damage, and strikingly, their absence resulted in enhanced pathology in murine models of the oral inflammatory disease periodontitis. Alterations in bacterial communities could not account for the increased disease severity seen in γδ T cell-deficient mice. Instead, gingival γδ T cells produced the wound healing associated cytokine amphiregulin, administration of which rescued the elevated oral pathology of tcrδ-/- mice. Collectively, our results identify γδ T cells as critical constituents of the immuno-surveillance network that safeguard gingival tissue homeostasis.}, } @article {pmid30279176, year = {2018}, author = {Briseño, CG and Satpathy, AT and Davidson, JT and Ferris, ST and Durai, V and Bagadia, P and O'Connor, KW and Theisen, DJ and Murphy, TL and Murphy, KM}, title = {Notch2-dependent DC2s mediate splenic germinal center responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10726-10731}, pmid = {30279176}, issn = {1091-6490}, support = {T32 CA009621/CA/NCI NIH HHS/United States ; F30 DK108498/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 AI007163/AI/NIAID NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Antigen Presentation/immunology ; B-Lymphocytes/*immunology/metabolism ; Cell Differentiation ; Cells, Cultured ; Dendritic Cells/*immunology/metabolism ; Erythrocytes/*immunology ; Germinal Center/*immunology/metabolism ; Immunity, Humoral/immunology ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Receptor, Notch2/*physiology ; Sheep ; Signal Transduction ; Spleen/*immunology/metabolism ; T-Lymphocytes, Helper-Inducer/*immunology/metabolism ; }, abstract = {CD4+ T follicular helper (TFH) cells support germinal center (GC) reactions promoting humoral immunity. Dendritic cell (DC) diversification into genetically distinct subsets allows for specialization in promoting responses against several types of pathogens. Whether any classical DC (cDC) subset is required for humoral immunity is unknown, however. We tested several genetic models that selectively ablate distinct DC subsets in mice for their impact on splenic GC reactions. We identified a requirement for Notch2-dependent cDC2s, but not Batf3-dependent cDC1s or Klf4-dependent cDC2s, in promoting TFH and GC B cell formation in response to sheep red blood cells and inactivated Listeria monocytogenes This effect was mediated independent of Il2ra and several Notch2-dependent genes expressed in cDC2s, including Stat4 and Havcr2 Notch2 signaling during cDC2 development also substantially reduced the efficiency of cDC2s for presentation of MHC class II-restricted antigens, limiting the strength of CD4 T cell activation. Together, these results demonstrate a nonredundant role for the Notch2-dependent cDC2 subset in supporting humoral immune responses.}, } @article {pmid30279175, year = {2018}, author = {Hale, ME}, title = {Making sense of sparse data with neural encoding strategies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10545-10547}, pmid = {30279175}, issn = {1091-6490}, mesh = {*Algorithms ; Mechanotransduction, Cellular ; Neurons/*physiology ; Statistics as Topic ; }, } @article {pmid30278451, year = {2018}, author = {Radhakrishnan, S and Literman, R and Neuwald, JL and Valenzuela, N}, title = {Thermal Response of Epigenetic Genes Informs Turtle Sex Determination with and without Sex Chromosomes.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000492188}, pmid = {30278451}, issn = {1661-5433}, abstract = {Vertebrate sexual fate can be established by environmental cues (e.g., temperature-dependent sex determination, TSD) or by genetic content (genotypic sex determination, GSD). While methylation is implicated in TSD, the influence of broader epigenetic processes in sexual development remains obscure. Here, we investigated for the first time the embryonic gonadal expression of the genome-wide epigenetic machinery in turtles, including genes and noncoding RNAs (ncRNAs) involved in DNA/histone acetylation, methylation, ubiquitination, phosphorylation, and RNAi. This machinery was active and differentially thermosensitive in TSD versus GSD (ZZ/ZW) turtles. Methylation and histone acetylation genes responded the strongest. The results suggest these working hypotheses: (i) TSD might be mediated by epigenetically controlled hormonal pathways (via acetylation, methylation, and ncRNAs), or by (ii) hormonally controlled epigenetic processes, and (iii) key epigenetic events prior to the canonical thermosensitive period may explain differences between TSD and GSD. Novel epigenetic candidate regulators other than methylation were identified, including previously unknown ncRNAs that could potentially mediate gonadogenesis. These findings illuminate the molecular ecology of reptilian sex determination and permitted hypothesis building to help guide future functional studies on the epigenetic transduction of external cues in TSD versus GSD systems.}, } @article {pmid30278254, year = {2019}, author = {Wu, LW and Chiba, H and Lees, DC and Ohshima, Y and Jeng, ML}, title = {Unravelling relationships among the shared stripes of sailors: Mitogenomic phylogeny of Limenitidini butterflies (Lepidoptera, Nymphalidae, Limenitidinae), focusing on the genera Athyma and Limenitis.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {60-66}, doi = {10.1016/j.ympev.2018.09.020}, pmid = {30278254}, issn = {1095-9513}, abstract = {The phylogenetic relationships of the nymphalid butterfly tribe Limenitidini are best known for the genera Limenitis and Adelpha, model taxa for evolutionary processes such as Batesian mimicry and rapid adaptive radiations. Whereas these American limenitidines have received the most attention, phylogenetic relationships of their Asian relatives are still controversial and largely unexplored. Even one of the largest genera in Asia, Athyma, is polyphyletic. To clarify the phylogenetic relationships of these Asian Limenitidini, a total of 53 representatives were sampled; 37 have their mitogenomes sequenced for the first time. Our phylogenetic results confirm that mitogenomic data provides well-resolved relationships at most major levels of the phylogeny, even using different partition schemes or different inference methods. Interestingly, our results show that some Athyma taxa are embedded within the genus Limenitis, whereas the genus Tacola, previously considered to be a synonym of Athyma, needs to be recognized as a valid clade. Additionally, the other Limenitidini genera in Asia (namely Tarattia, Litinga, Sumalia, Pandita and Patsuia) are now grouped either within Athyma or Limenitis, so these genera need to be sunk. Importantly, we also show that the mainly Old World Limenitis and entirely New World Adelpha are sister groups, confirming the relevance of Asian lineages to global studies of Limenitis evolution.}, } @article {pmid30278253, year = {2019}, author = {Strong, EE and Puillandre, N and Beu, AG and Castelin, M and Bouchet, P}, title = {Frogs and tuns and tritons - A molecular phylogeny and revised family classification of the predatory gastropod superfamily Tonnoidea (Caenogastropoda).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {18-34}, doi = {10.1016/j.ympev.2018.09.016}, pmid = {30278253}, issn = {1095-9513}, abstract = {The Tonnoidea is a moderately diverse group of large, predatory gastropods with ∼360 valid species. Known for their ability to secrete sulfuric acid, they use it to prey on a diversity of invertebrates, primarily echinoderms. Tonnoideans currently are classified in seven accepted families: the comparatively well known, shallow water Bursidae, Cassidae, Personidae, Ranellidae, and Tonnidae, and the lesser-known, deep water Laubierinidae and Pisanianuridae. We assembled a mitochondrial and nuclear gene (COI, 16S, 12S, 28S) dataset for ∼80 species and 38 genera currently recognized as valid. Bayesian analysis of the concatenated dataset recovered a monophyletic Tonnoidea, with Ficus as its sister group. Unexpectedly, Thalassocyon, currently classified in the Ficidae, was nested within the ingroup as the sister group to Distorsionella. Among currently recognized families, Tonnidae, Cassidae, Bursidae and Personidae were supported as monophyletic but the Ranellidae and Ranellinae were not, with Cymatiinae, Ranella and Charonia supported as three unrelated clades. The Laubierinidae and Pisanianuridae together form a monophyletic group. Although not all currently accepted genera have been included in the analysis, the new phylogeny is sufficiently robust and stable to the inclusion/exclusion of nonconserved regions to establish a revised family-level classification with nine families: Bursidae, Cassidae, Charoniidae, Cymatiidae, Laubierinidae, Personidae, Ranellidae, Thalassocyonidae and Tonnidae. The results reveal that many genera as presently circumscribed are para- or polyphyletic and, in some cases support the rescue of several genus-group names from synonymy (Austrosassia, Austrotriton, Laminilabrum, Lampadopsis, Personella, Proxicharonia, Tritonoranella) or conversely, support their synonymization (Biplex with Gyrineum). Several species complexes are also revealed that merit further investigation (e.g., Personidae: Distorsio decipiens, D. reticularis; Bursidae: Bursa tuberosissima; Cassidae: Echinophoria wyvillei, Galeodea bituminata, and Semicassis bisulcata). Consequently, despite their teleplanic larvae, the apparently circumglobal distribution of some tonnoidean species is the result of excessive synonymy. The superfamily is estimated to have diverged during the early Jurassic (∼186 Ma), with most families originating during a narrow ∼20 My window in Albian-Aptian times as part of the Mesozoic Marine Revolution.}, } @article {pmid30278252, year = {2019}, author = {Cole, ML and Raheem, DC and Villet, MH}, title = {Molecular phylogeny of Chondrocyclus (Gastropoda: Cyclophoridae), a widespread genus of sedentary, restricted-range snails.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {193-210}, doi = {10.1016/j.ympev.2018.09.018}, pmid = {30278252}, issn = {1095-9513}, abstract = {The genus Chondrocyclus Ancey, 1898 contains the majority of southern African members of the Cyclophoridae, a large family of operculate land snails. We present the first molecular phylogeny of the genus based on two mitochondrial genes (16S and CO1) and complement this with an appraisal of morphological characters relating to the shell and soft parts. Worn shells on which some descriptions and records of different species were based appear to be indistinguishable morphologically, creating taxonomic confusion. We show that Chondrocyclus s.l. underwent two major radiations, one Afromontane and the other largely coastal. Accordingly, we recommend a revision recognising two genera. Chondrocyclus s.s. contains four monophyletic lineages, each characterized by a combination of morphological features. The Afromontane group is shown to be a species complex; relationships within this complex could not be resolved due to insufficient DNA sequence data. The molecular data confirms the monophyly of seven currently recognised species and provides evidence for at least twelve undescribed species; the morphological data are broadly consistent with this finding. The morphological data suggest that the two species from countries to the north of South Africa should be removed from the genus, and that Chondrocyclus sensu lato is endemic to South Africa. The historical biogeography of this group of microhabitat specialists with poor dispersal abilities contributes an additional, phylogenetically independent taxon to our understanding of the processes generating biodiversity in southern Africa, a natural laboratory for palaeobiogeography. All taxa are narrow-range endemics, underlining the importance of conserving South Africa's threatened forest habitats.}, } @article {pmid30277517, year = {2018}, author = {Smalla, K and Cook, K and Djordjevic, SP and Klümper, U and Gillings, M}, title = {Environmental dimensions of antibiotic resistance: assessment of basic science gaps.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy195}, pmid = {30277517}, issn = {1574-6941}, abstract = {Antibiotic resistance is one of the major problems facing medical practice in the 21st century. Historical approaches to managing antibiotic resistance have often focused on individual patients, specific pathogens and particular resistance phenotypes. However, it is increasingly recognized that antibiotic resistance is a complex ecological and evolutionary problem. As such, understanding the dynamics of antibiotic resistance requires integration of data on the diverse mobile genetic elements often associated with antibiotic resistance genes, and their dissemination by various mechanisms of horizontal gene transfer between bacterial cells and environments. Most important is understanding the fate and effects of antibiotics at sub-inhibitory concentrations, and co-selection. This opinion paper identifies key knowledge gaps in our understanding of resistance phenomena, and outlines research needs that should be addressed to help us manage resistance into the future.}, } @article {pmid30277320, year = {2018}, author = {Dittmann, KK and Sonnenschein, EC and Egan, S and Gram, L and Bentzon-Tilia, M}, title = {Impact of Phaeobacter inhibens on marine eukaryote-associated microbial communities.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12698}, pmid = {30277320}, issn = {1758-2229}, support = {//Augustinus Fonden/ ; //Christian og Ottilia Brorsons Rejselegat for yngre videnskabsmaend og -kvinder/ ; 0603-00515B//Danish Council for Strategic research in Health, Food and Welfare/ ; //Oticon Fonden/ ; VKR023285//Villum Fonden/ ; //Fabrikant P.A. Fiskers foundation/ ; //Augustinus foundation/ ; //IDAs og Berg-Nielsens Studie- og Støttefond/ ; //Oticon foundation/ ; DNRF137//Danish National Research Foundation/ ; 0603-00515B//Danish Council for Strategic Research, Committee for Strategic Research in Health, Food and Welfare/ ; VKR023285//Villum Kann Rasmussen foundation/ ; //Technical University of Denmark/ ; }, abstract = {Bacteria-host interactions are universal in nature and have significant effects on host functionality. Bacterial secondary metabolites are believed to play key roles in such interactions as well as in interactions within the host-associated microbial community. Hence, prominent secondary metabolite-producing bacteria may be strong drivers of microbial community composition in natural host-associated microbiomes. This has, however, not been rigorously tested, and the purpose of this study was to investigate how the secondary metabolite producer Phaeobacter inhibens affects the diversity and composition of microbiomes associated with the microalga Emiliania huxleyi and the European flat oyster, Ostrea edulis. Roseobacters were indigenous to both communities exhibiting relative abundances between 2.8% and 7.0%. Addition of P. inhibens caused substantial changes in the overall structure of the low-complexity microbiome of E. huxleyi, but did not shape microbial community structure to the same degree in the more complex oyster microbiomes. Species-specific interactions occurred in both microbiomes and specifically the abundances of other putative secondary metabolite-producers such as vibrios and pseudoalteromonads were reduced. Thus, the impact of a bioactive strain like P. inhibens on host-associated microbiomes depends on the complexity and composition of the existing microbiome.}, } @article {pmid30277319, year = {2018}, author = {Wang, N and Luo, YW and Polimene, L and Zhang, R and Zheng, Q and Cai, R and Jiao, N}, title = {Contribution of structural recalcitrance to the formation of the deep oceanic dissolved organic carbon reservoir.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {711-717}, doi = {10.1111/1758-2229.12697}, pmid = {30277319}, issn = {1758-2229}, abstract = {The origin of the recalcitrant dissolved organic carbon (RDOC) reservoir in the deep ocean remains enigmatic. The structural recalcitrance hypothesis suggests that RDOC is formed by molecules that are chemically resistant to bacterial degradation. The dilution hypothesis claims that RDOC is formed from a large diversity of labile molecules that escape bacterial utilization due to their low concentrations, termed as RDOCc . To evaluate the relative contributions of these two mechanisms in determining the long-term persistence of RDOC, we model the dynamics of both structurally recalcitrant DOC and RDOCc based on previously published data that describes deep oceanic DOC degradation experiments. Our results demonstrate that the majority of DOC (84.5 ± 2.2%) in the deep ocean is structurally recalcitrant. The intrinsically labile DOC (i.e., labile DOC that rapidly consumed and RDOCc) accounts for a relatively small proportion and is consumed rapidly in the incubation experiments, in which 47.8 ± 3.2% of labile DOC and 21.9 ± 4.6% of RDOCc are consumed in 40 days. Our results suggest that the recalcitrance of RDOC is largely related to its chemical properties, whereas dilution plays a minor role in determining the persistence of deep-ocean DOC.}, } @article {pmid30277308, year = {2018}, author = {Buerger, P and Weynberg, KD and Wood-Charlson, EM and Sato, Y and Willis, BL and van Oppen, MJH}, title = {Novel T4 bacteriophages associated with black band disease in corals.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14432}, pmid = {30277308}, issn = {1462-2920}, support = {17625//AIMS@JCU Postgraduate Research Funding/ ; FS110200034//Australian Research Council/ ; FT100100088//Australian Research Council/ ; }, abstract = {Research into causative agents underlying coral disease have focused primarily on bacteria, whereas potential roles of viruses have been largely unaddressed. Bacteriophages may contribute to diseases through the lysogenic introduction of virulence genes into bacteria, or prevent diseases through lysis of bacterial pathogens. To identify candidate phages that may influence the pathogenicity of black band disease (BBD), communities of bacteria (16S rRNA) and T4-bacteriophages (gp23) were simultaneously profiled with amplicon sequencing among BBD-lesions and healthy-coral-tissue of Montipora hispida, as well as seawater (study site: the central Great Barrier Reef). Bacterial community compositions were distinct among BBD-lesions, healthy coral tissue and seawater samples, as observed in previous studies. Surprisingly, however, viral beta diversities based on both operational taxonomic unit (OTU)-compositions and overall viral community compositions of assigned taxa did not differ statistically between the BBD-lesions and healthy coral tissue. Nonetheless, relative abundances of three bacteriophage OTUs, affiliated to Cyanophage PRSM6 and Prochlorococcus phages P-SSM2, were significantly higher in BBD-lesions than in healthy tissue. These OTUs associated with BBD samples suggest the presence of bacteriophages that infect members of the cyanobacteria-dominated BBD community, and thus have potential roles in BBD pathogenicity.}, } @article {pmid30277305, year = {2019}, author = {Jauffrais, T and LeKieffre, C and Schweizer, M and Geslin, E and Metzger, E and Bernhard, JM and Jesus, B and Filipsson, HL and Maire, O and Meibom, A}, title = {Kleptoplastidic benthic foraminifera from aphotic habitats: insights into assimilation of inorganic C, N and S studied with sub-cellular resolution.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {125-141}, doi = {10.1111/1462-2920.14433}, pmid = {30277305}, issn = {1462-2920}, support = {EC2CO/LEFE project "ForChlo"//Centre National de la Recherche Scientifique/ ; //Region Pays de Loire/ ; 200021_149333//Swiss National Science Foundation/ ; //Université d'Angers/ ; //Woods Hole Oceanographic Institution/ ; }, abstract = {The assimilation of inorganic compounds in foraminiferal metabolism compared to predation or organic matter assimilation is unknown. Here, we investigate possible inorganic-compound assimilation in Nonionellina labradorica, a common kleptoplastidic benthic foraminifer from Arctic and North Atlantic sublittoral regions. The objectives were to identify the source of the foraminiferal kleptoplasts, assess their photosynthetic functionality in light and darkness and investigate inorganic nitrogen and sulfate assimilation. We used DNA barcoding of a ~ 830 bp fragment from the SSU rDNA to identify the kleptoplasts and correlated transmission electron microscopy and nanometre-scale secondary ion mass spectrometry (TEM-NanoSIMS) isotopic imaging to study 13 C-bicarbonate, 15 N-ammonium and 34 S-sulfate uptake. In addition, respiration rate measurements were determined to assess the response of N. labradorica to light. The DNA sequences established that over 80% of the kleptoplasts belonged to Thalassiosira (with 96%-99% identity), a cosmopolitan planktonic diatom. TEM-NanoSIMS imaging revealed degraded cytoplasm and an absence of 13 C assimilation in foraminifera exposed to light. Oxygen measurements showed higher respiration rates under light than dark conditions, and no O2 production was detected. These results indicate that the photosynthetic pathways in N. labradorica are not functional. Furthermore, N. labradorica assimilated both 15 N-ammonium and 34 S-sulfate into its cytoplasm, which suggests that foraminifera might have several ammonium or sulfate assimilation pathways, involving either the kleptoplasts or bona fide foraminiferal pathway(s) not yet identified.}, } @article {pmid30277299, year = {2019}, author = {Olofsson, M and Kourtchenko, O and Zetsche, EM and Marchant, HK and Whitehouse, MJ and Godhe, A and Ploug, H}, title = {High single-cell diversity in carbon and nitrogen assimilations by a chain-forming diatom across a century.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {142-151}, doi = {10.1111/1462-2920.14434}, pmid = {30277299}, issn = {1462-2920}, support = {910 MSCA_IF_GA_660481//Maria Skłodowska Curie Action, project/ ; 019-2012-2070//Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning/ ; VR:2017-03746//Swedish Research Council/ ; }, abstract = {Almost a century ago Redfield discovered a relatively constant ratio between carbon, nitrogen and phosphorus in particulate organic matter and nitrogen and phosphorus of dissolved nutrients in seawater. Since then, the riverine export of nitrogen to the ocean has increased 20 fold. High abundance of resting stages in sediment layers dated more than a century back indicate that the common planktonic diatom Skeletonema marinoi has endured this eutrophication. We germinated unique genotypes from resting stages originating from isotope-dated sediment layers (15 and 80 years old) in a eutrophied fjord. Using secondary ion mass spectrometry (SIMS) combined with stable isotopic tracers, we show that the cell-specific carbon and nitrogen assimilation rates vary by an order of magnitude on a single-cell level but are significantly correlated during the exponential growth phase, resulting in constant assimilation quota in cells with identical genotypes. The assimilation quota varies largely between different clones independent of age. We hypothesize that the success of S. marinoi in coastal waters may be explained by its high diversity of nutrient demand not only at a clone-specific level but also at the single-cell level, whereby the population can sustain and adapt to dynamic nutrient conditions in the environment.}, } @article {pmid30276581, year = {2018}, author = {Gall, JG}, title = {Herbert Macgregor (1933-2018).}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {4}, pages = {225-231}, doi = {10.1007/s10577-018-9586-z}, pmid = {30276581}, issn = {1573-6849}, support = {R01 GM033397/GM/NIGMS NIH HHS/United States ; }, } @article {pmid30275902, year = {2018}, author = {Wu, C and Park, JY and Guan, W and Pan, W}, title = {An adaptive gene-based test for methylation data.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {60}, pmid = {30275902}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; R01 GM113250/GM/NIGMS NIH HHS/United States ; R01 HL105397/HL/NHLBI NIH HHS/United States ; R01 HL116720/HL/NHLBI NIH HHS/United States ; }, abstract = {DNA methylation plays an important role in normal human development and disease. In epigenome-wide association studies (EWAS), a univariate test for association between a phenotype and each cytosine-phosphate-guanine (CpG) site has been widely used. Given the number of CpG sites tested in EWAS, a stringent significance cutoff is required to adjust for multiple testing; in addition, multiple nearby CpG sites may be associated with the phenotype, which is ignored by a univariate test. These two factors may contribute to the power loss of a univariate test. As an alternative, we propose applying an adaptive gene-based test that is powerful in genome-wide association studies (GWAS), called aSPUw, to EWAS for simultaneous testing on multiple CpG sites within or near a gene. We show its application to the GAW20 methylation data set.}, } @article {pmid30275901, year = {2018}, author = {Piette, ER and Moore, JH}, title = {Identification of epistatic interactions between the human RNA demethylases FTO and ALKBH5 with gene set enrichment analysis informed by differential methylation.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {59}, pmid = {30275901}, issn = {1753-6561}, support = {R01 AI116794/AI/NIAID NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; R01 LM009012/LM/NLM NIH HHS/United States ; R01 LM010098/LM/NLM NIH HHS/United States ; }, abstract = {The Genetic Analysis Workshop (GAW) presents an opportunity to collaboratively evaluate methodology relevant to current issues in genetic epidemiology. The GAW20 data combine real clinical trial data with fictitious epigenetic drug response endpoints. Considering the evidence suggesting that networks of interactions between many genes underlie complex phenotypes, we utilize differential methylation status to identify a relevant gene set for enrichment analysis and use this to infer potential biological function underlying drug response. We highlight the pertinence of considering the potential for widespread epistatic interactions in the absence of main effects, and present evidence of epistasis between single-nucleotide polymorphisms (SNPs) on the two RNA demethylases FTO and ALKBH5.}, } @article {pmid30275900, year = {2018}, author = {Veenstra, J and Kalsbeek, A and Koster, K and Ryder, N and Bos, A and Huisman, J and VanderBerg, L and VanderWoude, J and Tintle, NL}, title = {Epigenome wide association study of SNP-CpG interactions on changes in triglyceride levels after pharmaceutical intervention: a GAW20 analysis.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {58}, pmid = {30275900}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; R15 HG006915/HG/NHGRI NIH HHS/United States ; }, abstract = {In the search for an understanding of how genetic variation contributes to the heritability of common human disease, the potential role of epigenetic factors, such as methylation, is being explored with increasing frequency. Although standard analyses test for associations between methylation levels at individual cytosine-phosphate-guanine (CpG) sites and phenotypes of interest, some investigators have begun testing for methylation and how methylation may modulate the effects of genetic polymorphisms on phenotypes. In our analysis, we used both a genome-wide and candidate gene approach to investigate potential single-nucleotide polymorphism (SNP)-CpG interactions on changes in triglyceride levels. Although we were able to identify numerous loci of interest when using an exploratory significance threshold, we did not identify any significant interactions using a strict genome-wide significance threshold. We were also able to identify numerous loci using the candidate gene approach, in which we focused on 18 genes with prior evidence of association of triglyceride levels. In particular, we identified GALNT2 loci as containing potential CpG sites that moderate the impact of genetic polymorphisms on triglyceride levels. Further work is needed to provide clear guidance on analytic strategies for testing SNP-CpG interactions, although leveraging prior biological understanding may be needed to improve statistical power in data sets with smaller sample sizes.}, } @article {pmid30275899, year = {2018}, author = {Chen, Y and Peloso, GM and Dupuis, J}, title = {Evaluation of a phenotype imputation approach using GAW20 simulated data.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {56}, pmid = {30275899}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Statistical power, which is the probability of correctly rejecting a false null hypothesis, is a limitation of genome-wide association studies (GWAS). Sample size is a major component of statistical power that can be easily affected by missingness in phenotypic data and restrain the ability to detect associated single-nucleotide polymorphisms (SNPs) with small effect sizes. Although some phenotypes are hard to collect because of cost and loss to follow-up, correlated phenotypes that are easily collected can be leveraged for association analysis. In this paper, we evaluate a phenotype imputation method that incorporates family structure and correlation between multiple phenotypes using GAW20 simulated data. The distribution of missing values is derived using information contained in the missing sample's relatives and additional correlated phenotypes. We show that this imputation method can improve power in the association analysis compared with excluding observations with missing data, while achieving the correct Type I error rate. We also examine factors that may affect the imputation accuracy.}, } @article {pmid30275898, year = {2018}, author = {Peralta, JM and Blackburn, NB and Porto, A and Blangero, J and Charlesworth, J}, title = {Genome-wide linkage scan for loci influencing plasma triglyceride levels.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {52}, pmid = {30275898}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {We conducted a genome-wide linkage scan to detect loci that influence the levels of fasting triglycerides in plasma. Fasting triglyceride levels were available at 4 time points (visits), 2 pre- and 2 post-fenofibrate intervention. Multipoint identity-by-descent (MIBD) matrices were derived from genotypes using IBDLD. Variance-component linkage analyses were then conducted using SOLAR (Sequential Oligogenic Linkage Analysis Routines). We found evidence of linkage (logarithm of odds [LOD] ≥3) at 5 chromosomal regions with triglyceride levels in plasma. The highest LOD scores were observed for linkage to the estimated genetic value (additive genetic component) of the log-normalized triglyceride levels in plasma. Our results suggest that a chromosome 10 locus at 37 cM (LODpre = 3.01, LODpost = 3.72) influences fasting triglyceride levels in plasma regardless of the fenofibrate intervention, and that loci in chromosomes 1 at 170 cM and 4 at 24 cM ceases to affect the triglyceride levels when fenofibrate is present, while the regions in chromosomes 6 at 136 to 162 cM and 11 at 39 to 40 cM appear to influence triglyceride levels in response to fenofibrate.}, } @article {pmid30275897, year = {2018}, author = {Porto, A and Peralta, JM and Blackburn, NB and Blangero, J}, title = {Reliability of genomic predictions of complex human phenotypes.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {51}, pmid = {30275897}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Genome-wide association studies have helped us identify a wealth of genetic variants associated with complex human phenotypes. Because most variants explain a small portion of the total phenotypic variation, however, marker-based studies remain limited in their ability to predict such phenotypes. Here, we show how modern statistical genetic techniques borrowed from animal breeding can be employed to increase the accuracy of genomic prediction of complex phenotypes and the power of genetic mapping studies. Specifically, using the triglyceride data of the GAW20 data set, we apply genomic-best linear unbiased prediction (G-BLUP) methods to obtain empirical genetic values (EGVs) for each triglyceride phenotype and each individual. We then study 2 different factors that influence the prediction accuracy of G-BLUP for the analysis of human data: (a) the choice of kinship matrix, and (b) the overall level of relatedness. The resulting genetic values represent the total genetic component for the phenotype of interest and can be used to represent a trait without its environmental component. Finally, using empirical data, we demonstrate how this method can be used to increase the power of genetic mapping studies. In sum, our results show that dense genome-wide data can be used in a wider scope than previously anticipated.}, } @article {pmid30275896, year = {2018}, author = {Vander Woude, J and Huisman, J and Vander Berg, L and Veenstra, J and Bos, A and Kalsbeek, A and Koster, K and Ryder, N and Tintle, NL}, title = {Evaluating the performance of gene-based tests of genetic association when testing for association between methylation and change in triglyceride levels at GAW20.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {50}, pmid = {30275896}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; R15 HG006915/HG/NHGRI NIH HHS/United States ; }, abstract = {Although methylation data continues to rise in popularity, much is still unknown about how to best analyze methylation data in genome-wide analysis contexts. Given continuing interest in gene-based tests for next-generation sequencing data, we evaluated the performance of novel gene-based test statistics on simulated data from GAW20. Our analysis suggests that most of the gene-based tests are detecting real signals and maintaining the Type I error rate. The minimum p value and threshold-based tests performed well compared to single-marker tests in many cases, especially when the number of variants was relatively large with few true causal variants in the set.}, } @article {pmid30275895, year = {2018}, author = {Yasmeen, S and Burger, P and Friedrichs, S and Papiol, S and Bickeböller, H}, title = {Relating drug response to epigenetic and genetic markers using a region-based kernel score test.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {47}, pmid = {30275895}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {In GAW20, we investigated the association of specific genetic regions of interest (ROIs) with log-transformed triglyceride (TG) levels following lipid-lowering medication using epigenetic and genetic markers. The goal was to incorporate kernels for cytosine-phosphate-guanine (CpG) markers and compare the kernels to a purely parametric model. Post-treatment TG levels were investigated for post-methylation data at CpG sites and region-specific SNPs and adjusted for pre-treatment TG levels and age, in independent individuals only (real data: n = 150; simulated data, replicate 84: n = 111). In both data sets, our single-CpG-marker results using kernels and linear regression were in good agreement. In the real data, we investigated the introns of the CPT1A gene previously reported as associated with TG levels as separate ROIs, and were able to find hints of an association of cg17058475 and cg00574958 with post-treatment TG levels. In the simulated data, we investigated a total of 10 regions, in which the 5 causal and 5 non-causal markers lie, respectively, with increased methylation variances, yielding plausible results for the 3 window sizes. Overall, this indicates that kernels for CpG markers are feasible. An interaction regression model for the causal SNP with the nearest CpG marker identified an effect for the SNPs with the three greatest heritabilities simulated. The simulation model assumed full SNP effect only for unmethylated regions decreasing to zero in the case of full methylation. Thus, in the context of a clear candidate setting, interaction between epigenetic and genetic data may enhance information, albeit nominally, even with small sample sizes. Relieving the burden of multiple testing, developing kernels further to analyze data from multiple omics jointly is well warranted.}, } @article {pmid30275894, year = {2018}, author = {Xu, Z and Duan, Q and Cui, J and Qiu, Y and Jia, Q and Wu, C and Clarke, J}, title = {Analysis of genetic and nongenetic factors influencing triglycerides-lowering drug effects based on paired observations.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {46}, pmid = {30275894}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Obesity is a risk factor for heart disease, stroke, diabetes, high blood pressure, and other chronic diseases. Some drugs, including fenofibrate, are used to treat obesity or excessive weight by lowering the level of specific triglycerides. However, different groups have different drug sensitivities and, consequently, there are differences in drug effects. In this study, we assessed both genetic and nongenetic factors that influence drug responses and stratified patients into groups based on differential drug effect and sensitivity. Our methodology of investigating genetic factors and nongenetic factors is applicable to studying differential effects of other drugs, such as statins, and provides an approach to the development of personalized medicine.}, } @article {pmid30275893, year = {2018}, author = {Cox, JW and Patel, D and Chung, J and Zhu, C and Lent, S and Fisher, V and Pitsillides, A and Farrer, L and Zhang, X}, title = {An efficient analytic approach in genome-wide identification of methylation quantitative trait loci response to fenofibrate treatment.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {44}, pmid = {30275893}, issn = {1753-6561}, support = {R01 AG048927/AG/NIA NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; U01 AG032984/AG/NIA NIH HHS/United States ; }, abstract = {Background: The study of DNA methylation quantitative trait loci (meQTLs) helps dissect regulatory mechanisms underlying genetic associations of human diseases. In this study, we conducted the first genome-wide examination of genetic drivers of methylation variation in response to a triglyceride-lowering treatment with fenofibrate (response-meQTL) by using an efficient analytic approach.

Methods: Subjects (n = 429) from the GAW20 real data set with genotype and both pre- (visit 2) and post- (visit 4) fenofibrate treatment methylation measurements were included. Following the quality control steps of removing certain cytosine-phosphate-guanine (CpG) probes, the post-/premethylation changes (post/pre) were log transformed and the association was performed on 208,449 CpG sites. An additive linear mixed-effects model was used to test the association between each CpG probe and single nucleotide polymorphisms (SNPs) around ±1 Mb region, with age, sex, smoke, batch effect, and principal components included as covariates. Bonferroni correction was applied to define the significance threshold (p < 5.6 × 10- 10, given a total of 89,217,303 tests). Finally, we integrated our response-meQTL (re-meQTL) findings with the published genome-wide association study (GWAS) catalog of human diseases/traits.

Results: We identified 1087 SNPs as cis re-meQTLs associated with 610 CpG probes/sites located in 351 unique gene loci. Among these 1087 cis re-meQTL SNPs, 229 were unique and 6 were co-localized at 8 unique disease/trait loci reported in the GWAS catalog (enrichment p = 1.51 × 10- 23). Specifically, a lipid SNP, rs10903129, located in intron regions of gene TMEM57, was a re-meQTL (p = 3.12 × 10- 36) associated with the CpG probe cg09222892, which is in the upstream region of the gene RHCE, indicating a new target gene for rs10903129. In addition, we found that SNP rs12710728 has a suggestive association with cg17097782 (p = 1.77 × 10- 4), and that this SNP is in high linkage disequilibrium (LD) (R2 > 0.8) with rs7443270, which was previously reported to be associated with fenofibrate response (p = 5.00 × 10- 6).

Conclusions: By using a novel analytic approach, we efficiently identified thousands of cis re-meQTLs that provide a unique resource for further characterizing functional roles and gene targets of the SNPs that are most responsive to fenofibrate treatment. Our efficient analytic approach can be extended to large response quantitative trait locus studies with large sample sizes and multiple time points data.}, } @article {pmid30275892, year = {2018}, author = {Cantor, R and Navarro, L and Pan, C}, title = {Identifying fenofibrate responsive CpG sites.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {43}, pmid = {30275892}, issn = {1753-6561}, support = {P01 HL028481/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {As part of GAW20, we analyzed the familiality and variability of methylation to identify cytosine-phosphate-guanine (CpG) sites responsive to treatment with fenofibrate. Methylation was measured at approximately 450,000 sites in pedigree members, prior to and after 3 weeks of treatment. Initially, we aimed to identify responsive sites by analyzing the pre- and posttreatment methylation changes within individuals, but these data exhibited a confounding treatment/batch effect. We applied an alternative indirect approach by searching for CpG sites whose methylation levels exhibit a genetic response to the drug. We reasoned that these sites would exhibit highly familial and variable methylation levels posttreatment, but not pretreatment. Using a 0.1% threshold, posttreatment sibling correlation (scor) and standard deviation (SD) distributions share 16 outliers, while the corresponding pretreatment distributions share none. Comparing the pre- and posttreatment CpG outliers, 36 (8%) of SD distributions, and 449/450 (nearly 100%) of scor distributions differ. Combined, these results identify methylation sites within the KIAA1804 and ANAPC2 genes. Each gene also has a highly significant methylation quantitative trait locus (meQTL) (KIAA1804: p < 1e-200; ANAPC2: p < 3e-248), indicating that methylation levels at these CpG sites are driven by meQTL and fenofibrate.}, } @article {pmid30275891, year = {2018}, author = {Das, S and Mondal, PK and Ghosh, S and Mukhopadhyay, I}, title = {Family-based genome-wide association of inflammation biomarkers and fenofibrate treatment response in the GOLDN study.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {41}, pmid = {30275891}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {In this paper we analyzed whole-genome genetic information provided by GAW20 from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study for family data. Lipid levels such as triglycerides (TGs) and high-density lipoprotein (HDL) are measured at different time points before and after administration of an anti-inflammatory drug fenofibrate. Apart from that, the data contain some covariates and whole-genome genotype information. We propose 2 novel approaches based on Henderson's iterative mixed model to identify associated loci corresponding to (a) inflammatory biomarkers like TGs and HDLs together over time, and (b) the response to fenofibrate treatment. We developed a mixed-model approach using both TG and HDL phenotypes at all 4 time points for a genetic association study whereas we used TGs only to study genetic association with response to the drug. We expect that use of complete family data in a longitudinal framework under a single model involving the appropriate correlation structures would be able to exploit the maximum possible information contained in the sample. Our analysis of whole-genome single nucleotide polymorphisms (SNPs) and genomic regions corresponding to drug treatment finds no significant locus after multiple correction. Arguably, the moderately small sample size of the data set, as compared to the sample size usually used in genome-wide association studies (GWAS), could be a reason for such a result. Nevertheless, we report the top 20 SNPs associated with the phenotypes, and the top 20 SNPs and genomic regions associated with a response to fenofibrate treatment. Application of our methods to larger GWAS and further functional validation of the reported top SNPs and genomic regions might provide important biological insight into the genetic constitution of the trait.}, } @article {pmid30275890, year = {2018}, author = {Zhou, W and Lo, SH}, title = {Analysis of genotype by methylation interactions through sparsity-inducing regularized regression.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {40}, pmid = {30275890}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {In this paper, we consider the use of the least absolute shrinkage and selection operator (LASSO)-type regression techniques to detect important genetic or epigenetic loci in genome-wide association studies (GWAS) and epigenome-wide association studies (EWAS). We demonstrate how these techniques can be adapted to provide quantifiable uncertainty using stability selection, including explicit control of the family-wise error rate. We also consider variants of the LASSO, such as the group LASSO, to study genetic and epigenetic interactions. We use these techniques to reproduce some existing results on the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) data set, which collects from 991 individuals blood triglyceride and differential methylation at 464,000 cytosine-phosphate-guanine (CpG) sites and 761,000 single-nucleotide polymorphisms (SNPs), and to identify new research directions. Epigenome-wide and genome-wide models based on the LASSO are considered, as well as an interaction model limited to chromosome 11. The analyses replicate findings concerning 2 CpGs in carnitine palmitoyltransferase 1A (CPT1A). Some suggestions are made regarding potentially interesting directions for the analysis of genetic and epigenetic interactions.}, } @article {pmid30275889, year = {2018}, author = {Kulkarni, H and Mukhopadhyay, I and Ghosh, S}, title = {Transmission-based association mapping of triglyceride levels in a longitudinal framework using quasi-likelihood.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {39}, pmid = {30275889}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Complex genetic traits are often characterized by multiple quantitative phenotypes. Because values of such phenotypes vary over time, it is thought that analyses of longitudinal data on the phenotypes may lead to increased power in detecting genetic association. In this paper, we extend a transmission-based association test applying quasi-likelihood that has been developed by us to the longitudinal framework and to carry out a genome-wide association analysis of triglyceride levels based on the data provided in GAW20. We consider different phenotype definitions based on administration of fenofibrate and obtain significant association findings within genes involved in heart diseases.}, } @article {pmid30275888, year = {2018}, author = {Cherlin, S and Howey, RAJ and Cordell, HJ}, title = {Using penalized regression to predict phenotype from SNP data.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {38}, pmid = {30275888}, issn = {1753-6561}, support = {//Wellcome Trust/United Kingdom ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: In a typical genome-enabled prediction problem there are many more predictor variables than response variables. This prohibits the application of multiple linear regression, because the unique ordinary least squares estimators of the regression coefficients are not defined. To overcome this problem, penalized regression methods have been proposed, aiming at shrinking the coefficients toward zero.

Methods: We explore prediction of phenotype from single nucleotide polymorphism (SNP) data in the GAW20 data set using a penalized regression approach (LASSO [least absolute shrinkage and selection operator] regression). We use 10-fold cross-validation to assess predictive performance and 10-fold nested cross-validation to specify a penalty parameter.

Results: By analyzing approximately 600,000 SNPs we find that, when the sample size comprises a few hundred individuals, SNP effects are heavily penalized, resulting in a poor predictive performance. Increasing the sample size to a few thousand individuals results in a much smaller penalization of the true effects, thus greatly improving the prediction.

Conclusions: LASSO regression results in a heavy shrinkage of the regression coefficients, and also requires large sample sizes (several thousand individuals) to achieve good prediction.}, } @article {pmid30275887, year = {2018}, author = {Hu, K and Li, J}, title = {Detection and analysis of CpG sites with multimodal DNA methylation level distributions and their relationships with SNPs.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {36}, pmid = {30275887}, issn = {1753-6561}, support = {R01 DC012380/DC/NIDCD NIH HHS/United States ; R03 HG008632/HG/NHGRI NIH HHS/United States ; }, abstract = {DNA methylation levels at cytosine-phosphate-guanine (CpG) sites with multimodal distributions among different samples have been reported recently. One possible explanation for such variability is that genetic variants might affect epigenetic variation. One obvious case is that mutations such as single-nucleotide polymorphisms (SNPs) interrupt CpG sites, resulting in different DNA methylation levels for different genotypes. However, the relationship between genetic variations and epigenetic differences has not been studied thoroughly, partially because of the lack of powerful and robust methods to survey genome-wide CpG sites with multimodal methylation level distributions (mmCpGs). In this article, we develop a Gaussian mixture-model clustering (GMMC)-based approach to systematically detect all mmCpGs across the genome based on the GAW20 data set. In total, 3785 and 3847 mmCpGs have been identified in pre- and posttreatment data sets, respectively. Result analysis shows that approximately 68 to 70% of mmCpGs detected from unrelated individuals either have direct overlaps with SNPs or have associations with nearby SNPs, suggesting a strong correlation between SNPs and mmCpGs. Comparison with an existing approach illustrates that our GMMC-based method is more consistent when the number of samples decreases. In conclusion, mmCpGs may reveal important connections between genetics and epigenetics and they should be carefully identified and evaluated.}, } @article {pmid30275886, year = {2018}, author = {Aslibekyan, S and Almasy, L and Province, MA and Absher, DM and Arnett, DK}, title = {Data for GAW20: genome-wide DNA sequence variation and epigenome-wide DNA methylation before and after fenofibrate treatment in a family study of metabolic phenotypes.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {35}, pmid = {30275886}, issn = {1753-6561}, support = {K01 HL136700/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; R01 HL091357/HL/NHLBI NIH HHS/United States ; R01 HL104135/HL/NHLBI NIH HHS/United States ; }, abstract = {GAW20 provided participants with an opportunity to comprehensively examine genetic and epigenetic variation among related individuals in the context of drug treatment response. GAW20 used data from 188 families (N = 1105) participating in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study (clinicaltrials.gov identifier NCT00083369), which included CD4+ T-cell DNA methylation at 463,995 cytosine-phosphate-guanine (CpG) sites measured before and after a 3-week treatment with fenofibrate, single-nucleotide variation at 906,600 loci, metabolic syndrome components ascertained before and after the drug intervention, and relevant covariates. All GOLDN participants were of European descent, with an average age of 48 years. In addition, approximately half were women and approximately 40% met the diagnostic criteria for metabolic syndrome. Unique advantages of the GAW20data set included longitudinal (3 weeks apart) measurements of DNA methylation, the opportunity to explore the contributions of both genotype and DNA methylation to the interindividual variability in drug treatment response, and the familial relationships between study participants. The principal disadvantage of GAW20/GOLDN data was the spurious correlation between batch effects and fenofibrate effects on methylation, which arose because the pre- and posttreatment methylation data were generated and normalized separately, and any attempts to remove time-dependent technical artifacts would also remove biologically meaningful changes brought on by fenofibrate. Despite this limitation, the GAW20 data set offered informative, multilayered omics data collected in a large population-based study of common disease traits, which resulted in creative approaches to integration and analysis of inherited human variation.}, } @article {pmid30275885, year = {2018}, author = {Fuady, AM and Tissier, RLM and Houwing-Duistermaat, JJ}, title = {Genome-wide analysis in multiple-case families: assessing the relationship between triglyceride and methylation.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {33}, pmid = {30275885}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {The main goal of this paper is to estimate the effect of triglyceride levels on methylation of cytosine-phosphate-guanine (CpG) sites in multiple-case families. These families are selected because they have 2 or more cases of metabolic syndrome (primary phenotype). The methylations at the CpG sites are the secondary phenotypes. Ascertainment corrections are needed when there is an association between the primary and secondary phenotype. We will apply the newly developed secondary phenotype analysis for multiple-case family studies to identify CpG sites where methylations are influenced by triglyceride levels. Our second goal is to compare the performance of the naïve approach, which ignores the sampling of the families, SOLAR (Sequential Oligogenic Linkage Analysis Routines), which adjusts for ascertainment via probands, and the secondary phenotype approach. The analysis of possible CpG sites associated with triglyceride levels shows results consistent with the literature when using the secondary phenotype approach. Overall, the secondary phenotype approach performed well, but the comparison of the different approaches does not show significant differences between them. However, for genome-wide applications, we recommend using the secondary phenotype approach when there is an association between primary and secondary phenotypes, and to use the naïve approach otherwise.}, } @article {pmid30275884, year = {2018}, author = {Canty, AJ and Paterson, AD}, title = {Evidence of batch effects masking treatment effect in GAW20 methylation data.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {32}, pmid = {30275884}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; R01 HL104135/HL/NHLBI NIH HHS/United States ; U01 HL072524/HL/NHLBI NIH HHS/United States ; }, abstract = {Using the real data set from GAW20, we examined changes in the distribution of DNA methylation before and after treatment. Paired analysis of differences in both mean and variance had grossly inflated type 1 error, suggesting either a very large number of changes across the entire epigenome or major non-biological issues, such as batch effects. Separate analysis of Infinium I and II probes indicated differences in the paired t-test statistics between these two types of probes. Examination of combined principal components showed that the first and fourth principal components discriminate between the before and after treatment measurements, further evidencing the presence of batch effects that make any conclusions about treatment effect suspect.}, } @article {pmid30275883, year = {2018}, author = {Nustad, HE and Page, CM and Reiner, AH and Zucknick, M and LeBlanc, M}, title = {A Bayesian mixed modeling approach for estimating heritability.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {31}, pmid = {30275883}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: A Bayesian mixed model approach using integrated nested Laplace approximations (INLA) allows us to construct flexible models that can account for pedigree structure. Using these models, we estimate genome-wide patterns of DNA methylation heritability (h2), which are currently not well understood, as well as h2 of blood lipid measurements.

Methods: We included individuals from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study with Infinium 450 K cytosine-phosphate-guanine (CpG) methylation and blood lipid data pre- and posttreatment with fenofibrate in families with up to three-generation pedigrees. For genome-wide patterns, we constructed 1 model per CpG with methylation as the response variable, with a random effect to model kinship, and age and gender as fixed effects.

Results: In total, 425,791 CpG sites pre-, but only 199,027 CpG sites posttreatment were found to have nonzero heritability. Across these CpG sites, the distributions of h2 estimates are similar in pre- and posttreatment (pre: median = 0.31, interquartile range [IQR] = 0.16; post: median = 0.34, IQR = 0.20). Blood lipid h2 estimates were similar pre- and posttreatment with overlapping 95% credibility intervals. Heritability was nonzero for treatment effect, that is, the difference between pre- and posttreatment blood lipids. Estimates for triglycerides h2 are 0.48 (pre), 0.42 (post), and 0.21 (difference); likewise for high-density lipoprotein cholesterol h2 the estimates are 0.61, 0.68, and 0.10.

Conclusions: We show that with INLA, a fully Bayesian approach to estimate DNA methylation h2 is possible on a genome-wide scale. This provides uncertainty assessment of the estimates, and allows us to perform model selection via deviance information criterion (DIC) to identify CpGs with strong evidence for nonzero heritability.}, } @article {pmid30275882, year = {2018}, author = {Wang, B and DeStefano, AL and Lin, H}, title = {Integrative methylation score to identify epigenetic modifications associated with lipid changes resulting from fenofibrate treatment in families.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {28}, pmid = {30275882}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Epigenome-wide association studies (EWAS) have traditionally focused on the association test of single epigenetic markers with complex traits. However, it is possible that multiple cytosine-phosphate-guanine (CpG) sites at the same locus could jointly exert their effects on human traits. Therefore, a region-based test that combines multiple markers could be more powerful. We used 2 different region-based tests to investigate the association between changes in DNA methylation and drug response, including the median methylation level test (MMLT) and sequence kernel association test (SKAT). No genes were found to be significantly associated with the drug response (for triglycerides, the false discovery rate ranged from 0.855 to 0.999; for high-density lipoprotein cholesterol, and the false discovery rate ranged from 0.584 to 0.915). Further evidence is needed to explore potential application of gene-level methylation association analysis.}, } @article {pmid30275881, year = {2018}, author = {Lim, E and Xu, H and Wu, P and Posner, D and Wu, J and Peloso, GM and Pitsillides, AN and DeStefano, AL and Adrienne Cupples, L and Liu, CT}, title = {Network analysis of drug effect on triglyceride-associated DNA methylation.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {27}, pmid = {30275881}, issn = {1753-6561}, support = {R01 DK089256/DK/NIDDK NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: DNA methylation, an epigenetic modification, can be affected by environmental factors and thus regulate gene expression levels that can lead to alterations of certain phenotypes. Network analysis has been used successfully to discover gene sets that are expressed differently across multiple disease states and suggest possible pathways of disease progression. We applied this framework to compare DNA methylation levels before and after lipid-lowering medication and to identify modules that differ topologically between the two time points, revealing the association between lipid medication and these triglyceride-related methylation sites.

Methods: We performed quality control using beta-mixture quantile normalization on 463,995 cytosine-phosphate-guanine (CpG) sites and deleted problematic sites, resulting in 423,004 probes. We identified 14,850 probes that were nominally associated with triglycerides prior to treatment and performed weighted gene correlation network analysis (WGCNA) to construct pre- and posttreatment methylation networks of these probes. We then applied both WGCNA module preservation and generalized Hamming distance (GHD) to identify modules with topological differences between the pre- and posttreatment. For modules with structural changes between 2 time points, we performed pathway-enrichment analysis to gain further insight into the biological function of the genes from these modules.

Results: Six triglyceride-associated modules were identified using pretreatment methylation probes. The same 3 modules were not preserved in posttreatment data using both the module-preservation and the GHD methods. Top-enriched pathways for the 3 differentially methylated modules are sphingolipid signaling pathway, proteoglycans in cancer, and metabolic pathways (p values < 0.005). One module in particular included an enrichment of lipid-related pathways among the top results.

Conclusions: The same 3 modules, which were differentially methylated between pre- and posttreatment, were identified using both WGCNA module-preservation and GHD methods. Pathway analysis revealed that triglyceride-associated modules contain groups of genes that are involved in lipid signaling and metabolism. These 3 modules may provide insight into the effect of fenofibrate on changes in triglyceride levels and these methylation sites.}, } @article {pmid30275880, year = {2018}, author = {Kraja, AT and An, P and Lenzini, P and Lin, SJ and Williams, C and Hicks, JE and Warwick Daw, E and Province, MA}, title = {Simulation of a medication and methylation effects on triglycerides in the Genetic Analysis Workshop 20.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {25}, pmid = {30275880}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; R01 HL117078/HL/NHLBI NIH HHS/United States ; }, abstract = {The GAW20 simulation data set is based upon the companion Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study fenofibrate clinical trial data set that forms the real data example for GAW20. The simulated data problem consists of 200 simulated replications of what might happen if we were to repeat the GOLDN clinical trial 200 independent times, for these exact same subjects, but using a new fictitious drug (called "genomethate") that has a pharmaco-epigenetic effect on triglyceride response. For each replication, the pre-genomethate values at visits 1 and 2 are constant (ie, pedigree structures, age, sex, all phenotypes, covariates, genome-wide association study (GWAS) genotypes, and visit 2 methylation values), the same as the real GOLDN data across all 200 replications. Only the post-genomethate treatment data (ie, methylation and triglyceride levels for visits 3 and 4) change across the 200 replications. We postulate a growth curve pharmaco-epigenetic response model, in which each patient's response to genomethate treatment is individualized, and is dependent upon their genotype as well as the methylation state for key genes.}, } @article {pmid30275879, year = {2018}, author = {Sayols-Baixeras, S and Tiwari, HK and Aslibekyan, SW}, title = {Disentangling associations between DNA methylation and blood lipids: a Mendelian randomization approach.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {23}, pmid = {30275879}, issn = {1753-6561}, support = {K01 HL136700/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: DNA methylation is an epigenetic mechanism that has been proposed as a possible link between genetic and environmental determinants of disease. Prior studies reported robust associations between the methylation of specific cytosine-phosphate-guanine (CpG) sites and plasma lipids, namely triglycerides (TGs) and high-density lipoprotein cholesterol (HDL-C). However, the causality of the observed association remains elusive, hampered by weak instrumental variables for methylation status.

Aim: We present a novel application of the elastic net approach to implement a bidirectional Mendelian randomization approach to inferring causal relationships between candidate CpGs and plasma lipids in GAW20 data.

Methods: We used DNA methylation, TGs, and HDL-C measured during the visit 2. Based on prior findings, we selected 5 methylation markers (cg00574958, cg07504977, cg06690548, cg19693031, and cg03717755) related to TGs, 2 markers (cg09572125 and cg02650017) related to HDL-C, and 2 markers (cg06500161 and cg11024682) related to both traits. We implemented an elastic net approach to improve the selection of the genetic instrument for the methylation markers, followed by bidirectional Mendelian randomization 2-stage least-squares regression.

Results: We observed causal effects of blood fasting TGs on the methylation levels of cg00574958 (CPT1A) and cg06690548 (SLC7A11). For cg00574958, our findings were also consistent with the reverse direction of association, that is, from CPT1A methylation to TGs.

Conclusions: Current evidence does not rule out either direction of association between the methylation of the cg00574958 CPT1A locus and plasma TGs, highlighting the complexity of lipid homeostasis. We also demonstrated a novel approach to improve instrument selection in DNA methylation studies.}, } @article {pmid30275878, year = {2018}, author = {Justice, AE and Howard, AG and Fernández-Rhodes, L and Graff, M and Tao, R and North, KE}, title = {Direct and indirect genetic effects on triglycerides through omics and correlated phenotypes.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {22}, pmid = {30275878}, issn = {1753-6561}, support = {K99 HL130580/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; T32 HD007168/HD/NICHD NIH HHS/United States ; T32 HL007055/HL/NHLBI NIH HHS/United States ; }, abstract = {Even though there has been great success in identifying lipid-associated single-nucleotide polymorphisms (SNPs), the mechanisms through which the SNPs act on each trait are poorly understood. The emergence of large, complex biological data sets in well-characterized cohort studies offers an opportunity to investigate the genetic effects on trait variability as a way of informing the causal genes and biochemical pathways that are involved in lipoprotein metabolism. However, methods for simultaneously analyzing multiple omics, environmental exposures, and longitudinally measured, correlated phenotypes are lacking. The purpose of our study was to demonstrate the utility of the structural equation modeling (SEM) approach to inform our understanding of the pathways by which genetic variants lead to disease risk. With the SEM method, we examine multiple pathways directly and indirectly through previously identified triglyceride (TG)-associated SNPs, methylation, and high-density lipoprotein (HDL), including sex, age, and smoking behavior, while adding in biologically plausible direct and indirect pathways. We observed significant SNP effects (P < 0.05 and directionally consistent) on TGs at visit 4 (TG4) for five loci, including rs645040 (DOCK7), rs964184 (ZPR1/ZNF259), rs4765127 (ZNF664), rs1121980 (FTO), and rs10401969 (SUGP1). Across these loci, we identify three with strong evidence of an indirect genetic effect on TG4 through HDL, one with evidence of pleiotropic effect on HDL and TG4, and one variant that acts on TG4 indirectly through a nearby methylation site. Such information can be used to prioritize candidate genes in regions of interest, inform mechanisms of action of methylation effects, and highlight possible genes with pleiotropic effects.}, } @article {pmid30275877, year = {2018}, author = {Jiang, L and Zhao, K and Klein, K and Canty, AJ and Oualkacha, K and Greenwood, CMT}, title = {Investigating potential causal relationships between SNPs, DNA methylation and HDL.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {20}, pmid = {30275877}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Using data on 680 patients from the GAW20 real data set, we conducted Mendelian randomization (MR) studies to explore the causal relationships between methylation levels at selected probes (cytosine-phosphate-guanine sites [CpGs]) and high-density lipoprotein (HDL) changes (ΔHDL) using single-nucleotide polymorphisms (SNPs) as instrumental variables. Several methods were used to estimate the causal effects at CpGs of interest on ΔHDL, including a newly developed method that we call constrained instrumental variables (CIV). CIV performs automatic SNP selection while providing estimates of causal effects adjusted for possible pleiotropy, when the potentially-pleiotropic phenotypes are measured. For CpGs in or near the 10 genes identified as associated with ΔHDL using a family-based VC-score test, we compared CIV to Egger regression and the two-stage least squares (TSLS) method. All 3 approaches selected at least 1CpG in 2 genes-RNMT;C18orf19 and C6orf141-as showing a causal relationship with ΔHDL.}, } @article {pmid30275876, year = {2018}, author = {Howey, RAJ and Cordell, HJ}, title = {Application of Bayesian networks to GAW20 genetic and blood lipid data.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {19}, pmid = {30275876}, issn = {1753-6561}, support = {//Wellcome Trust/United Kingdom ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: Bayesian networks have been proposed as a way to identify possible causal relationships between measured variables based on their conditional dependencies and independencies. We explored the use of Bayesian network analyses applied to the GAW20 data to identify possible causal relationships between differential methylation of cytosine-phosphate-guanine dinucleotides (CpGs), single-nucleotide polymorphisms (SNPs), and blood lipid trait (triglycerides [TGs]).

Methods: After initial exploratory linear regression analyses, 2 Bayesian networks analyses were performed. First, we used the real data and modeled the effects of 4 CpGs previously found to be associated with TGs in the Genetics of Lipid Lowering Drugs and Diet Network Study (GOLDN). Second, we used the simulated data and modeled the effect of a fictional lipid modifying drug with 5 known causal SNPs and 5 corresponding CpGs.

Results: In the real data we show that relationships are present between the CpGs, TGs, and other variables-age, sex, and center. In the simulated data, we show, using linear regression, that no CpGs and only 1 SNP were associated with a change in TG levels, and, using Bayesian network analysis, that relationships are present between the change in TG levels and most SNPs, but not with CpGs.

Conclusions: Even when the causal relationships between variables are known, as with the simulated data, if the relationships are not strong then it is challenging to reproduce them in a Bayesian network.}, } @article {pmid30275560, year = {2018}, author = {Vera, C}, title = {Farmers transformed how we investigate climate.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {9}, doi = {10.1038/d41586-018-06856-6}, pmid = {30275560}, issn = {1476-4687}, mesh = {Agriculture/*methods ; Animals ; Argentina ; Atlantic Ocean ; Atmosphere/chemistry ; *Climate ; Droughts/statistics & numerical data ; *Farmers ; Floods/statistics & numerical data ; Forecasting/methods ; Hydrology/*methods ; Rain ; *Research ; *Research Personnel ; Temperature ; Workforce ; }, } @article {pmid30275559, year = {2018}, author = {Dance, A}, title = {On the record.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {153-155}, doi = {10.1038/d41586-018-06871-7}, pmid = {30275559}, issn = {1476-4687}, mesh = {Career Choice ; *Mummies ; Skull ; *Stereolithography ; Tomography, X-Ray Computed ; }, } @article {pmid30275558, year = {2018}, author = {}, title = {Record-breaking battery saves sunshine for a rainy day.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {11}, doi = {10.1038/d41586-018-06839-7}, pmid = {30275558}, issn = {1476-4687}, } @article {pmid30275556, year = {2018}, author = {}, title = {Jupiter takes an annual pummelling from the Solar System.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {10}, doi = {10.1038/d41586-018-06851-x}, pmid = {30275556}, issn = {1476-4687}, } @article {pmid30275555, year = {2018}, author = {}, title = {An aggressive cancer's road to conquest.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {10}, doi = {10.1038/d41586-018-06823-1}, pmid = {30275555}, issn = {1476-4687}, } @article {pmid30275554, year = {2018}, author = {}, title = {Infants attuned to others' fear become altruistic toddlers.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {10}, doi = {10.1038/d41586-018-06797-0}, pmid = {30275554}, issn = {1476-4687}, } @article {pmid30275553, year = {2018}, author = {}, title = {Gene-snipping tool swats mosquitoes.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {11}, doi = {10.1038/d41586-018-06796-1}, pmid = {30275553}, issn = {1476-4687}, } @article {pmid30275552, year = {2018}, author = {}, title = {The hidden talent of a dangerous Icelandic volcano.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {11}, doi = {10.1038/d41586-018-06807-1}, pmid = {30275552}, issn = {1476-4687}, } @article {pmid30275551, year = {2018}, author = {Rabbany, SY and Rafii, S}, title = {Blood flow forces liver growth.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {42-43}, doi = {10.1038/d41586-018-06741-2}, pmid = {30275551}, issn = {1476-4687}, } @article {pmid30275550, year = {2018}, author = {Liblau, RS}, title = {Put to sleep by immune cells.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {46-48}, doi = {10.1038/d41586-018-06666-w}, pmid = {30275550}, issn = {1476-4687}, mesh = {Autoantigens ; Humans ; Narcolepsy ; Neurons ; *Orexins ; Sleep ; *T-Lymphocytes ; }, } @article {pmid30275549, year = {2018}, author = {Cahoon, LA and Freitag, NE}, title = {The electrifying energy of gut microbes.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {43-44}, doi = {10.1038/d41586-018-06180-z}, pmid = {30275549}, issn = {1476-4687}, mesh = {*Electrons ; Flavins ; *Gastrointestinal Tract ; Gram-Positive Bacteria ; }, } @article {pmid30275548, year = {2018}, author = {Pikarsky, E}, title = {Neighbourhood deaths cause a switch in cancer subtype.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {45-46}, doi = {10.1038/d41586-018-06217-3}, pmid = {30275548}, issn = {1476-4687}, mesh = {Death ; Humans ; Liver Neoplasms ; *Residence Characteristics ; *Socioeconomic Factors ; }, } @article {pmid30275531, year = {2018}, author = {Klarin, D and Damrauer, SM and Cho, K and Sun, YV and Teslovich, TM and Honerlaw, J and Gagnon, DR and DuVall, SL and Li, J and Peloso, GM and Chaffin, M and Small, AM and Huang, J and Tang, H and Lynch, JA and Ho, YL and Liu, DJ and Emdin, CA and Li, AH and Huffman, JE and Lee, JS and Natarajan, P and Chowdhury, R and Saleheen, D and Vujkovic, M and Baras, A and Pyarajan, S and Di Angelantonio, E and Neale, BM and Naheed, A and Khera, AV and Danesh, J and Chang, KM and Abecasis, G and Willer, C and Dewey, FE and Carey, DJ and , and , and , and , and Concato, J and Gaziano, JM and O'Donnell, CJ and Tsao, PS and Kathiresan, S and Rader, DJ and Wilson, PWF and Assimes, TL}, title = {Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1514-1523}, doi = {10.1038/s41588-018-0222-9}, pmid = {30275531}, issn = {1546-1718}, support = {K01 HL125751/HL/NHLBI NIH HHS/United States ; K08 HL140203/HL/NHLBI NIH HHS/United States ; R01 HL127564/HL/NHLBI NIH HHS/United States ; T32 HL007734/HL/NHLBI NIH HHS/United States ; }, abstract = {The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).}, } @article {pmid30275530, year = {2018}, author = {Lilue, J and Doran, AG and Fiddes, IT and Abrudan, M and Armstrong, J and Bennett, R and Chow, W and Collins, J and Collins, S and Czechanski, A and Danecek, P and Diekhans, M and Dolle, DD and Dunn, M and Durbin, R and Earl, D and Ferguson-Smith, A and Flicek, P and Flint, J and Frankish, A and Fu, B and Gerstein, M and Gilbert, J and Goodstadt, L and Harrow, J and Howe, K and Ibarra-Soria, X and Kolmogorov, M and Lelliott, CJ and Logan, DW and Loveland, J and Mathews, CE and Mott, R and Muir, P and Nachtweide, S and Navarro, FCP and Odom, DT and Park, N and Pelan, S and Pham, SK and Quail, M and Reinholdt, L and Romoth, L and Shirley, L and Sisu, C and Sjoberg-Herrera, M and Stanke, M and Steward, C and Thomas, M and Threadgold, G and Thybert, D and Torrance, J and Wong, K and Wood, J and Yalcin, B and Yang, F and Adams, DJ and Paten, B and Keane, TM}, title = {Sixteen diverse laboratory mouse reference genomes define strain-specific haplotypes and novel functional loci.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1574-1583}, pmid = {30275530}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; R01 DK074656/DK/NIDDK NIH HHS/United States ; U41 HG007234/HG/NHGRI NIH HHS/United States ; U42 OD010921/OD/NIH HHS/United States ; }, abstract = {We report full-length draft de novo genome assemblies for 16 widely used inbred mouse strains and find extensive strain-specific haplotype variation. We identify and characterize 2,567 regions on the current mouse reference genome exhibiting the greatest sequence diversity. These regions are enriched for genes involved in pathogen defence and immunity and exhibit enrichment of transposable elements and signatures of recent retrotransposition events. Combinations of alleles and genes unique to an individual strain are commonly observed at these loci, reflecting distinct strain phenotypes. We used these genomes to improve the mouse reference genome, resulting in the completion of 10 new gene structures. Also, 62 new coding loci were added to the reference genome annotation. These genomes identified a large, previously unannotated, gene (Efcab3-like) encoding 5,874 amino acids. Mutant Efcab3-like mice display anomalies in multiple brain regions, suggesting a possible role for this gene in the regulation of brain development.}, } @article {pmid30275521, year = {2018}, author = {Hofer, U}, title = {The majority is uncultured.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {716-717}, doi = {10.1038/s41579-018-0097-x}, pmid = {30275521}, issn = {1740-1534}, } @article {pmid30275520, year = {2018}, author = {York, A}, title = {Making matters worse.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {659}, doi = {10.1038/s41579-018-0094-0}, pmid = {30275520}, issn = {1740-1534}, } @article {pmid30275513, year = {2018}, author = {Santin, YG and Doan, T and Lebrun, R and Espinosa, L and Journet, L and Cascales, E}, title = {In vivo TssA proximity labelling during type VI secretion biogenesis reveals TagA as a protein that stops and holds the sheath.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1304-1313}, doi = {10.1038/s41564-018-0234-3}, pmid = {30275513}, issn = {2058-5276}, abstract = {The type VI secretion system (T6SS) is a multiprotein weapon used by bacteria to destroy competitor cells. The T6SS contractile sheath wraps an effector-loaded syringe that is injected into the target cell. This tail structure assembles onto the baseplate that is docked to the membrane complex. In enteroaggregative Escherichia coli, TssA plays a central role at each stage of the T6SS assembly pathway by stabilizing the baseplate and coordinating the polymerization of the tail. Here we adapted an assay based on APEX2-dependent biotinylation to identify the proximity partners of TssA in vivo. By using stage-blocking mutations, we define the temporal contacts of TssA during T6SS biogenesis. This proteomic mapping approach also revealed an additional partner of TssA, TagA. We show that TagA is a cytosolic protein tightly associated with the membrane. Analyses of sheath dynamics further demonstrate that TagA captures the distal end of the sheath to stop its polymerization and to maintain it under the extended conformation.}, } @article {pmid30275512, year = {2018}, author = {Bueno, E and Sit, B and Waldor, MK and Cava, F}, title = {Anaerobic nitrate reduction divergently governs population expansion of the enteropathogen Vibrio cholerae.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1346-1353}, doi = {10.1038/s41564-018-0253-0}, pmid = {30275512}, issn = {2058-5276}, abstract = {To survive and proliferate in the absence of oxygen, many enteric pathogens can undergo anaerobic respiration within the host by using nitrate (NO3-) as an electron acceptor1,2. In these bacteria, NO3- is typically reduced by a nitrate reductase to nitrite (NO2-), a toxic intermediate that is further reduced by a nitrite reductase3. However, Vibrio cholerae, the intestinal pathogen that causes cholera, lacks a nitrite reductase, leading to NO2- accumulation during nitrate reduction4. Thus, V. cholerae is thought to be unable to undergo NO3--dependent anaerobic respiration4. Here, we show that during hypoxic growth, NO3- reduction in V. cholerae divergently affects bacterial fitness in a manner dependent on environmental pH. Remarkably, in alkaline conditions, V. cholerae can reduce NO3- to support population growth. Conversely, in acidic conditions, accumulation of NO2- from NO3- reduction simultaneously limits population expansion and preserves cell viability by lowering fermentative acid production. Interestingly, other bacterial species such as Salmonella typhimurium, enterohaemorrhagic Escherichia coli (EHEC) and Citrobacter rodentium also reproduced this pH-dependent response, suggesting that this mechanism might be conserved within enteric pathogens. Our findings explain how a bacterial pathogen can use a single redox reaction to divergently regulate population expansion depending on the fluctuating environmental pH.}, } @article {pmid30275511, year = {2018}, author = {Omattage, NS and Deng, Z and Pinkner, JS and Dodson, KW and Almqvist, F and Yuan, P and Hultgren, SJ}, title = {Structural basis for usher activation and intramolecular subunit transfer in P pilus biogenesis in Escherichia coli.}, journal = {Nature microbiology}, volume = {3}, number = {12}, pages = {1362-1368}, pmid = {30275511}, issn = {2058-5276}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; R01 AI029549/AI/NIAID NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 AI048689/AI/NIAID NIH HHS/United States ; S10 OD021527/OD/NIH HHS/United States ; }, abstract = {Chaperone-usher pathway pili are extracellular proteinaceous fibres ubiquitously found on Gram-negative bacteria, and mediate host-pathogen interactions and biofilm formation critical in pathogenesis in numerous human diseases1. During pilus assembly, an outer membrane macromolecular machine called the usher catalyses pilus biogenesis from the individual subunits that are delivered as chaperone-subunit complexes in the periplasm. The usher orchestrates pilus assembly using all five functional domains: a 24-stranded transmembrane β-barrel translocation domain, a β-sandwich plug domain, an amino-terminal periplasmic domain and two carboxy-terminal periplasmic domains (CTD1 and CTD2)2-6. Despite extensive structural and functional characterization, the mechanism by which the usher is activated to initiate pilus biogenesis is unknown. Here, we present the crystal structure of the full-length PapC usher from Escherichia coli in complex with its cognate PapDG chaperone-subunit complex in a pre-activation state, elucidating molecular details of how the usher is specifically engaged by allosteric interactions with its substrate preceding activation and how the usher facilitates the transfer of subunits from the amino-terminal periplasmic domain to the CTDs during pilus assembly. This work elucidates the intricate workings of a molecular machine that catalyses chaperone-usher pathway pilus assembly and opens the door for the development of potent inhibitors to block pilus biogenesis.}, } @article {pmid30275480, year = {2018}, author = {Song, XP and Hansen, MC and Stehman, SV and Potapov, PV and Tyukavina, A and Vermote, EF and Townshend, JR}, title = {Author Correction: Global land change from 1982 to 2016.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {E26}, doi = {10.1038/s41586-018-0573-5}, pmid = {30275480}, issn = {1476-4687}, abstract = {In this Letter, errors in Supplementary Table 1 have been corrected.}, } @article {pmid30275479, year = {2018}, author = {Yamagishi, Y and Sakuno, T and Shimura, M and Watanabe, Y}, title = {Author Correction: Heterochromatin links to centromeric protection by recruiting shugoshin.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {E21}, doi = {10.1038/s41586-018-0529-9}, pmid = {30275479}, issn = {1476-4687}, abstract = {An Amendment to this Letter has been published and is linked from the HTML version of this paper.}, } @article {pmid30275478, year = {2018}, author = {Tada, K and Susumu, H and Sakuno, T and Watanabe, Y}, title = {Author Correction: Condensin association with histone H2A shapes mitotic chromosomes.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {E20}, doi = {10.1038/s41586-018-0528-x}, pmid = {30275478}, issn = {1476-4687}, abstract = {An Amendment to this Article has been published and is linked from the HTML version of this paper.}, } @article {pmid30275477, year = {2018}, author = {Kim, J and Ishiguro, KI and Nambu, A and Akiyoshi, B and Yokobayashi, S and Kagami, A and Ishiguro, T and Pendas, AM and Takeda, N and Sakakibara, Y and Kitajima, TS and Tanno, Y and Sakuno, T and Watanabe, Y}, title = {Author Correction: Meikin is a conserved regulator of meiosis-I-specific kinetochore function.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {E23}, doi = {10.1038/s41586-018-0530-3}, pmid = {30275477}, issn = {1476-4687}, abstract = {An Amendment to this Article has been published and is linked from the HTML version of this paper.}, } @article {pmid30275476, year = {2018}, author = {Wisotzki, L and Bacon, R and Brinchmann, J and Cantalupo, S and Richter, P and Schaye, J and Schmidt, KB and Urrutia, T and Weilbacher, PM and Akhlaghi, M and Bouché, N and Contini, T and Guiderdoni, B and Herenz, EC and Inami, H and Kerutt, J and Leclercq, F and Marino, RA and Maseda, M and Monreal-Ibero, A and Nanayakkara, T and Richard, J and Saust, R and Steinmetz, M and Wendt, M}, title = {Nearly all the sky is covered by Lyman-α emission around high-redshift galaxies.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {229-232}, doi = {10.1038/s41586-018-0564-6}, pmid = {30275476}, issn = {1476-4687}, abstract = {Galaxies are surrounded by large reservoirs of gas, mostly hydrogen, that are fed by inflows from the intergalactic medium and by outflows from galactic winds. Absorption-line measurements along the lines of sight to bright and rare background quasars indicate that this circumgalactic medium extends far beyond the starlight seen in galaxies, but very little is known about its spatial distribution. The Lyman-α transition of atomic hydrogen at a wavelength of 121.6 nanometres is an important tracer of warm (about 104 kelvin) gas in and around galaxies, especially at cosmological redshifts greater than about 1.6 at which the spectral line becomes observable from the ground. Tracing cosmic hydrogen through its Lyman-α emission has been a long-standing goal of observational astrophysics1-3, but the extremely low surface brightness of the spatially extended emission is a formidable obstacle. A new window into circumgalactic environments was recently opened by the discovery of ubiquitous extended Lyman-α emission from hydrogen around high-redshift galaxies4,5. Such measurements were previously limited to especially favourable systems6-8 or to the use of massive statistical averaging9,10 because of the faintness of this emission. Here we report observations of low-surface-brightness Lyman-α emission surrounding faint galaxies at redshifts between 3 and 6. We find that the projected sky coverage approaches 100 per cent. The corresponding rate of incidence (the mean number of Lyman-α emitters penetrated by any arbitrary line of sight) is well above unity and similar to the incidence rate of high-column-density absorbers frequently detected in the spectra of distant quasars11-14. This similarity suggests that most circumgalactic atomic hydrogen at these redshifts has now been detected in emission.}, } @article {pmid30275466, year = {2018}, author = {Firth, JA and Cole, EF and Ioannou, CC and Quinn, JL and Aplin, LM and Culina, A and McMahon, K and Sheldon, BC}, title = {Personality shapes pair bonding in a wild bird social system.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1696-1699}, pmid = {30275466}, issn = {2397-334X}, abstract = {Mated pair bonds are integral to many animal societies, yet how individual variation in behaviour influences their formation remains largely unknown. In a population of wild great tits (Parus major), we show that personality shapes pair bonding: proactive males formed stronger pre-breeding pair bonds by meeting their future partners sooner and increasing their relationship strength at a faster rate. As a result, proactive males sampled fewer potential mates. Thus, personality may have important implications for social relationship dynamics and emergent social structure.}, } @article {pmid30275465, year = {2018}, author = {Czorlich, Y and Aykanat, T and Erkinaro, J and Orell, P and Primmer, CR}, title = {Rapid sex-specific evolution of age at maturity is shaped by genetic architecture in Atlantic salmon.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1800-1807}, doi = {10.1038/s41559-018-0681-5}, pmid = {30275465}, issn = {2397-334X}, abstract = {Understanding the mechanisms by which populations adapt to their environments is a fundamental aim in biology. However, it remains challenging to identify the genetic basis of traits, provide evidence of genetic changes and quantify phenotypic responses. Age at maturity in Atlantic salmon represents an ideal trait to study contemporary adaptive evolution as it has been associated with a single locus in the vgll3 region and has also strongly changed in recent decades. Here, we provide an empirical example of contemporary adaptive evolution of a large-effect locus driving contrasting sex-specific evolutionary responses at the phenotypic level. We identified an 18% decrease in the vgll3 allele associated with late maturity in a large and diverse salmon population over 36 years, induced by sex-specific selection during sea migration. Those genetic changes resulted in a significant evolutionary response only in males, due to sex-specific dominance patterns and vgll3 allelic effects. The vgll3 allelic and dominance effects differed greatly in a second population and were likely to generate different selection and evolutionary patterns. Our study highlights the importance of knowledge of genetic architecture to better understand fitness trait evolution and phenotypic diversity. It also emphasizes the potential role of adaptive evolution in the trend towards earlier maturation observed in numerous Atlantic salmon populations worldwide.}, } @article {pmid30275338, year = {2018}, author = {Massana-Cid, H and Codina, J and Pagonabarraga, I and Tierno, P}, title = {Active apolar doping determines routes to colloidal clusters and gels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10618-10623}, pmid = {30275338}, issn = {1091-6490}, abstract = {Collections of interacting active particles, self-propelling or not, have shown remarkable phenomena including the emergence of dynamic patterns across different length scales, from animal groups to vibrated grains, microtubules, bacteria, and chemical- or field-driven colloids. Burgeoning experimental and simulation activities are now exploring the possibility of realizing solid and stable structures from passive elements that are assembled by a few active dopants. Here we show that such an elusive task may be accomplished by using a small amount of apolar dopants, namely synthetic active but not self-propelling units. We use blue light to rapidly assemble 2D colloidal clusters and gels via nonequilibrium diffusiophoresis, where microscopic hematite dockers form long-living interstitial bonds that strongly glue passive silica microspheres. By varying the relative fraction of doping, we uncover a rich phase diagram including ordered and disordered clusters, space-filling gels, and bicontinuous structures formed by filamentary dockers percolating through a solid network of silica spheres. We characterize the slow relaxation and dynamic arrest of the different phases via correlation and scattering functions. Our findings provide a pathway toward the rapid engineering of mesoscopic gels and clusters via active colloidal doping.}, } @article {pmid30275337, year = {2018}, author = {Ling, L and Raikhel, AS}, title = {Serotonin signaling regulates insulin-like peptides for growth, reproduction, and metabolism in the disease vector Aedes aegypti.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9822-E9831}, pmid = {30275337}, issn = {1091-6490}, support = {R01 AI036959/AI/NIAID NIH HHS/United States ; }, mesh = {Aedes/*physiology ; Animals ; CRISPR-Cas Systems ; Female ; Insect Proteins/*metabolism ; Insulin/*metabolism ; Mosquito Vectors/*physiology ; Peptide Fragments/*metabolism ; Receptors, Serotonin/chemistry/genetics/*metabolism ; *Reproduction ; Serotonin/*metabolism ; Signal Transduction ; }, abstract = {Disease-transmitting female mosquitoes require a vertebrate blood meal to produce their eggs. An obligatory hematophagous lifestyle, rapid reproduction, and existence of a large number of transmittable diseases make mosquitoes the world's deadliest animals. Attaining optimal body size and nutritional status is critical for mosquitoes to become reproductively competent and effective disease vectors. We report that blood feeding boosts serotonin concentration and elevates the serotonin receptor Aa5HT2B (Aedes aegypti 5-hydroxytryptamine receptor, type 2B) transcript level in the fat-body, an insect analog of the vertebrate liver and adipose tissue. Aa5HT2B gene disruption using the CRISPR-Cas9 gene-editing approach led to a decreased body size, postponed development, shortened lifespan, retarded ovarian growth, and dramatically diminished lipid accumulation. Expression of the insulin-like peptide (ILP) genes ilp2 and ilp6 was down-regulated while that of ilp5 and ilp4 was up-regulated in response to Aa5HT2B disruption. CRISPR-Cas9 disruption of ilp2 or ilp6 resulted in adverse phenotypes similar to those of Aa5HT2B disruption, while ilp5 CRISPR-Cas9 disruption had exactly the opposite effect on growth and metabolism, with significantly increased body size and elevated lipid stores. Simultaneous CRISPR-Cas9 disruption of Aa5HT2B and ilp5 rescued these phenotypic manifestations. Aa5HT2B RNAi silencing rendered ilp6 insensitive to serotonin treatment in the cultured fat-body, suggesting a regulatory link between Aa5HT2B and ILP6. Moreover, CRISPR-Cas9 ilp6 disruption affects expression of ilp-2, -5, and -4, pointing out on a possible role of ILP6 as a mediator of the Aa5HT2B action.}, } @article {pmid30275336, year = {2018}, author = {Sago, CD and Lokugamage, MP and Paunovska, K and Vanover, DA and Monaco, CM and Shah, NN and Gamboa Castro, M and Anderson, SE and Rudoltz, TG and Lando, GN and Munnilal Tiwari, P and Kirschman, JL and Willett, N and Jang, YC and Santangelo, PJ and Bryksin, AV and Dahlman, JE}, title = {High-throughput in vivo screen of functional mRNA delivery identifies nanoparticles for endothelial cell gene editing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9944-E9952}, pmid = {30275336}, issn = {1091-6490}, support = {T32 EB006343/EB/NIBIB NIH HHS/United States ; T32 EB021962/EB/NIBIB NIH HHS/United States ; T32 GM008433/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *CRISPR-Cas Systems ; Cells, Cultured ; Endothelial Cells/cytology/*metabolism ; *Gene Editing ; *Gene Transfer Techniques ; HEK293 Cells ; Hepatocytes/cytology/metabolism ; High-Throughput Screening Assays ; Humans ; Lipids/*chemistry ; Mice ; Mice, Inbred C57BL ; Nanoparticles/*administration & dosage/chemistry ; RNA, Guide/chemistry/*genetics ; RNA, Messenger/chemistry/*genetics ; }, abstract = {Dysfunctional endothelium causes more disease than any other cell type. Systemically administered RNA delivery to nonliver tissues remains challenging, in large part because there is no high-throughput method to identify nanoparticles that deliver functional mRNA to cells in vivo. Here we report a system capable of simultaneously quantifying how >100 lipid nanoparticles (LNPs) deliver mRNA that is translated into functional protein. Using this system (named FIND), we measured how >250 LNPs delivered mRNA to multiple cell types in vivo and identified 7C2 and 7C3, two LNPs that efficiently deliver siRNA, single-guide RNA (sgRNA), and mRNA to endothelial cells. The 7C3 delivered Cas9 mRNA and sgRNA to splenic endothelial cells as efficiently as hepatocytes, distinguishing it from LNPs that deliver Cas9 mRNA and sgRNA to hepatocytes more than other cell types. These data demonstrate that FIND can identify nanoparticles with novel tropisms in vivo.}, } @article {pmid30275335, year = {2018}, author = {Li, D and Wang, YL}, title = {Coordination of cell migration mediated by site-dependent cell-cell contact.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10678-10683}, pmid = {30275335}, issn = {1091-6490}, support = {R01 GM118998/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Adhesion ; *Cell Communication ; *Cell Movement ; Cells, Cultured ; *Contact Inhibition ; Kidney Tubules/cytology/*physiology ; Rats ; Wnt Signaling Pathway ; }, abstract = {Contact inhibition of locomotion (CIL), the repulsive response of cells upon cell-cell contact, has been the predominant paradigm for contact-mediated responses. However, it is difficult for CIL alone to account for the complex behavior of cells within a multicellular environment, where cells often migrate in cohorts such as sheets, clusters, and streams. Although cell-cell adhesion and mechanical interactions play a role, how individual cells coordinate their migration within a multicellular environment remains unclear. Using micropatterned substrates to guide cell migration and manipulate cell-cell contact, we show that contacts between different regions of cells elicit different responses. Repulsive responses were limited to interaction with the head of a migrating cell, while contact with the tail of a neighboring cell promoted migration toward the tail. The latter behavior, termed contact following of locomotion (CFL), required the Wnt signaling pathway. Inhibition of the Wnt pathway disrupted not only CFL but also collective migration of epithelial cells, without affecting the migration of individual cells. In contrast, inhibition of myosin II with blebbistatin disrupted the migration of both individual epithelial cells and collectives. We propose that CFL, in conjunction with CIL, plays a major role in guiding and coordinating cell migration within a multicellular environment.}, } @article {pmid30275334, year = {2018}, author = {Schick, A and Kassen, R}, title = {Rapid diversification of Pseudomonas aeruginosa in cystic fibrosis lung-like conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10714-10719}, pmid = {30275334}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; Biofilms/growth & development ; *Biological Evolution ; Cystic Fibrosis/epidemiology/*microbiology/pathology ; Humans ; Lung/*microbiology ; *Nutrition Assessment ; Phenotype ; Pseudomonas Infections/*complications/microbiology ; Pseudomonas aeruginosa/*classification/isolation & purification/*pathogenicity ; }, abstract = {Chronic infection of the cystic fibrosis (CF) airway by the opportunistic pathogen Pseudomonas aeruginosa is the leading cause of morbidity and mortality for adult CF patients. Prolonged infections are accompanied by adaptation of P. aeruginosa to the unique conditions of the CF lung environment, as well as marked diversification of the pathogen into phenotypically and genetically distinct strains that can coexist for years within a patient. Little is known, however, about the causes of this diversification and its impact on patient health. Here, we show experimentally that, consistent with ecological theory of diversification, the nutritional conditions of the CF airway can cause rapid and extensive diversification of P. aeruginosa Mucin, the substance responsible for the increased viscosity associated with the thick mucus layer in the CF airway, had little impact on within-population diversification but did promote divergence among populations. Furthermore, in vitro evolution recapitulated traits thought to be hallmarks of chronic infection, including reduced motility and increased biofilm formation, and the range of phenotypes observed in a collection of clinical isolates. Our results suggest that nutritional complexity and reduced dispersal can drive evolutionary diversification of P. aeruginosa independent of other features of the CF lung such as an active immune system or the presence of competing microbial species. We suggest that diversification, by generating extensive phenotypic and genetic variation on which selection can act, may be a key first step in the development of chronic infections.}, } @article {pmid30275333, year = {2018}, author = {Ghuman, AS and Fiez, JA}, title = {Parcellating the structure and function of the reading circuit.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10542-10544}, pmid = {30275333}, issn = {1091-6490}, support = {K18 DC014577/DC/NIDCD NIH HHS/United States ; R01 MH107797/MH/NIMH NIH HHS/United States ; }, mesh = {*Cerebral Cortex ; *Reading ; }, } @article {pmid30275332, year = {2018}, author = {Graef, M}, title = {Membrane tethering by the autophagy ATG2A-WIPI4 complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10540-10541}, pmid = {30275332}, issn = {1091-6490}, mesh = {*Autophagy ; *Autophagy-Related Proteins ; Membrane Fusion ; Phagosomes ; }, } @article {pmid30275331, year = {2018}, author = {Bertuzzi, M and Chang, W and Ampatzis, K}, title = {Adult spinal motoneurons change their neurotransmitter phenotype to control locomotion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9926-E9933}, pmid = {30275331}, issn = {1091-6490}, mesh = {Aging ; Animals ; Behavior, Animal ; Glutamic Acid/*metabolism ; *Locomotion ; Motor Neurons/cytology/*physiology ; Neuromuscular Junction/*physiology ; Neurotransmitter Agents/metabolism ; Phenotype ; Spinal Cord Injuries/*physiopathology ; Synapses/*physiology ; Zebrafish ; }, abstract = {A particularly essential determinant of a neuron's functionality is its neurotransmitter phenotype. While the prevailing view is that neurotransmitter phenotypes are fixed and determined early during development, a growing body of evidence suggests that neurons retain the ability to switch between different neurotransmitters. However, such changes are considered unlikely in motoneurons due to their crucial functional role in animals' behavior. Here we describe the expression and dynamics of glutamatergic neurotransmission in the adult zebrafish spinal motoneuron circuit assembly. We demonstrate that part of the fast motoneurons retain the ability to switch their neurotransmitter phenotype under physiological (exercise/training) and pathophysiological (spinal cord injury) conditions to corelease glutamate in the neuromuscular junctions to enhance animals' motor output. Our findings suggest that motoneuron neurotransmitter switching is an important plasticity-bestowing mechanism in the reconfiguration of spinal circuits that control movements.}, } @article {pmid30275330, year = {2018}, author = {Heusser, SA and Lycksell, M and Wang, X and McComas, SE and Howard, RJ and Lindahl, E}, title = {Allosteric potentiation of a ligand-gated ion channel is mediated by access to a deep membrane-facing cavity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10672-10677}, pmid = {30275330}, issn = {1091-6490}, mesh = {Allosteric Regulation ; Anesthetics, Intravenous/*pharmacology ; Binding Sites ; Cell Membrane/drug effects/*metabolism ; Cyanobacteria/drug effects/*metabolism ; Ion Channel Gating/*drug effects ; Ligand-Gated Ion Channels/chemistry/genetics/*metabolism ; Ligands ; Membrane Potentials ; Models, Molecular ; Molecular Dynamics Simulation ; Propofol/*pharmacology ; Protein Binding ; }, abstract = {Theories of general anesthesia have shifted in focus from bulk lipid effects to specific interactions with membrane proteins. Target receptors include several subtypes of pentameric ligand-gated ion channels; however, structures of physiologically relevant proteins in this family have yet to define anesthetic binding at high resolution. Recent cocrystal structures of the bacterial protein GLIC provide snapshots of state-dependent binding sites for the common surgical agent propofol (PFL), offering a detailed model system for anesthetic modulation. Here, we combine molecular dynamics and oocyte electrophysiology to reveal differential motion and modulation upon modification of a transmembrane binding site within each GLIC subunit. WT channels exhibited net inhibition by PFL, and a contraction of the cavity away from the pore-lining M2 helix in the absence of drug. Conversely, in GLIC variants exhibiting net PFL potentiation, the cavity was persistently expanded and proximal to M2. Mutations designed to favor this deepened site enabled sensitivity even to subclinical concentrations of PFL, and a uniquely prolonged mode of potentiation evident up to ∼30 min after washout. Dependence of these prolonged effects on exposure time implicated the membrane as a reservoir for a lipid-accessible binding site. However, at the highest measured concentrations, potentiation appeared to be masked by an acute inhibitory effect, consistent with the presence of a discrete, water-accessible site of inhibition. These results support a multisite model of transmembrane allosteric modulation, including a possible link between lipid- and receptor-based theories that could inform the development of new anesthetics.}, } @article {pmid30275329, year = {2018}, author = {So, M and Elso, CM and Tresoldi, E and Pakusch, M and Pathiraja, V and Wentworth, JM and Harrison, LC and Krishnamurthy, B and Thomas, HE and Rodda, C and Cameron, FJ and McMahon, J and Kay, TWH and Mannering, SI}, title = {Proinsulin C-peptide is an autoantigen in people with type 1 diabetes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10732-10737}, pmid = {30275329}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Autoantigens/*immunology ; C-Peptide/*immunology/*metabolism ; CD4-Positive T-Lymphocytes/*immunology ; Cells, Cultured ; Child ; Child, Preschool ; Diabetes Mellitus, Type 1/*diagnosis/immunology/metabolism ; HLA Antigens/*immunology ; Humans ; Islets of Langerhans/*immunology ; Middle Aged ; Proinsulin/*immunology ; Young Adult ; }, abstract = {Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing beta cells, found within the islets of Langerhans in the pancreas, are destroyed by islet-infiltrating T cells. Identifying the antigenic targets of beta-cell reactive T cells is critical to gain insight into the pathogenesis of T1D and develop antigen-specific immunotherapies. Several lines of evidence indicate that insulin is an important target of T cells in T1D. Because many human islet-infiltrating CD4+ T cells recognize C-peptide-derived epitopes, we hypothesized that full-length C-peptide (PI33-63), the peptide excised from proinsulin as it is converted to insulin, is a target of CD4+ T cells in people with T1D. CD4+ T cell responses to full-length C-peptide were detected in the blood of: 14 of 23 (>60%) people with recent-onset T1D, 2 of 15 (>13%) people with long-standing T1D, and 1 of 13 (<8%) HLA-matched people without T1D. C-peptide-specific CD4+ T cell clones, isolated from six people with T1D, recognized epitopes from the entire 31 amino acids of C-peptide. Eighty-six percent (19 of 22) of the C-peptide-specific clones were restricted by HLA-DQ8, HLA-DQ2, HLA-DQ8trans, or HLA-DQ2trans, HLA alleles strongly associated with risk of T1D. We also found that full-length C-peptide was a much more potent agonist of some CD4+ T cell clones than an 18mer peptide encompassing the cognate epitope. Collectively, our findings indicate that proinsulin C-peptide is a key target of autoreactive CD4+ T cells in T1D. Hence, full-length C-peptide is a promising candidate for antigen-specific immunotherapy in T1D.}, } @article {pmid30275328, year = {2018}, author = {Puente-Sánchez, F and Arce-Rodríguez, A and Oggerin, M and García-Villadangos, M and Moreno-Paz, M and Blanco, Y and Rodríguez, N and Bird, L and Lincoln, SA and Tornos, F and Prieto-Ballesteros, O and Freeman, KH and Pieper, DH and Timmis, KN and Amils, R and Parro, V}, title = {Viable cyanobacteria in the deep continental subsurface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10702-10707}, pmid = {30275328}, issn = {1091-6490}, mesh = {Biological Evolution ; Cyanobacteria/genetics/*growth & development/metabolism ; *Ecosystem ; Geologic Sediments/*analysis ; *Metagenomics ; *Microscopy, Fluorescence ; *Protein Array Analysis ; }, abstract = {Cyanobacteria are ecologically versatile microorganisms inhabiting most environments, ranging from marine systems to arid deserts. Although they possess several pathways for light-independent energy generation, until now their ecological range appeared to be restricted to environments with at least occasional exposure to sunlight. Here we present molecular, microscopic, and metagenomic evidence that cyanobacteria predominate in deep subsurface rock samples from the Iberian Pyrite Belt Mars analog (southwestern Spain). Metagenomics showed the potential for a hydrogen-based lithoautotrophic cyanobacterial metabolism. Collectively, our results suggest that they may play an important role as primary producers within the deep-Earth biosphere. Our description of this previously unknown ecological niche for cyanobacteria paves the way for models on their origin and evolution, as well as on their potential presence in current or primitive biospheres in other planetary bodies, and on the extant, primitive, and putative extraterrestrial biospheres.}, } @article {pmid30275327, year = {2018}, author = {Li, Y and Qin, B and Shen, Y and Zhang, F and Liu, C and You, H and Du, G and Tang, D and Cheng, Z}, title = {HEIP1 regulates crossover formation during meiosis in rice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10810-10815}, pmid = {30275327}, issn = {1091-6490}, mesh = {Chromosomes, Plant ; *Crossing Over, Genetic ; *Meiosis ; Oryza/*genetics ; Plant Proteins/*genetics ; Recombination, Genetic ; }, abstract = {During meiosis, the number of double-strand breaks (DSBs) far exceeds the final number of crossovers (COs). Therefore, to identify proteins involved in determining which of these DSBs repaired into COs is critical in understanding the mechanism of CO control. Across species, HEI10-related proteins play important roles in CO formation. Here, through screening for HEI10-interacting proteins via a yeast two-hybrid system, we identify a CO protein HEI10 Interaction Protein 1 (HEIP1) in rice. HEIP1 colocalizes with HEI10 in a dynamic fashion along the meiotic chromosomes and specially localizes onto crossover sites from late pachytene to diplotene. Between these two proteins, HEI10 is required for the loading of HEIP1, but not vice versa. Moreover, mutations of the HEIP1 gene cause the severe reduction of chiasma frequency, whereas early homologous recombination processes are not disturbed and synapsis proceeds normally. HEIP1 interacts directly with ZIP4 and MSH5. In addition, the loading of HEIP1 depends on ZIP4, but not on MER3, MSH4, or MSH5. Together, our results suggest that HEIP1 may be a member of the ZMM group and acts as a key element regulating CO formation.}, } @article {pmid30275326, year = {2018}, author = {Ji, Z and Zhang, H and Liu, H and Yaghi, OM and Yang, P}, title = {Cytoprotective metal-organic frameworks for anaerobic bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10582-10587}, pmid = {30275326}, issn = {1091-6490}, mesh = {Cell Survival ; *Cytoprotection ; Metal-Organic Frameworks/*chemistry ; Moorella/*growth & development ; Oxidative Stress ; Photosynthesis ; Surface Properties ; Zirconium/*chemistry ; }, abstract = {We report a strategy to uniformly wrap Morella thermoacetica bacteria with a metal-organic framework (MOF) monolayer of nanometer thickness for cytoprotection in artificial photosynthesis. The catalytic activity of the MOF enclosure toward decomposition of reactive oxygen species (ROS) reduces the death of strictly anaerobic bacteria by fivefold in the presence of 21% O2, and enables the cytoprotected bacteria to continuously produce acetate from CO2 fixation under oxidative stress. The high definition of the MOF-bacteria interface involving direct bonding between phosphate units on the cell surface and zirconium clusters on MOF monolayer, provides for enhancement of life throughout reproduction. The dynamic nature of the MOF wrapping allows for cell elongation and separation, including spontaneous covering of the newly grown cell surface. The open-metal sites on the zirconium clusters lead to 600 times more efficient ROS decomposition compared with zirconia nanoparticles.}, } @article {pmid30275325, year = {2018}, author = {Zheng, W and Gilleaudeau, GJ and Kah, LC and Anbar, AD}, title = {Mercury isotope signatures record photic zone euxinia in the Mesoproterozoic ocean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10594-10599}, pmid = {30275325}, issn = {1091-6490}, abstract = {Photic zone euxinia (PZE) is a condition where anoxic, H2S-rich waters occur in the photic zone (PZ). PZE has been invoked as an impediment to the evolution of complex life on early Earth and as a kill mechanism for Phanerozoic mass extinctions. Here, we investigate the potential application of mercury (Hg) stable isotopes in marine sedimentary rocks as a proxy for PZE by measuring Hg isotope compositions in late Mesoproterozoic (∼1.1 Ga) shales that have independent evidence of PZE during discrete intervals. Strikingly, a significantly negative shift of Hg mass-independent isotope fractionation (MIF) was observed during euxinic intervals, suggesting changes in Hg sources or transformations in oceans coincident with the development of PZE. We propose that the negative shift of Hg MIF was most likely caused by (i) photoreduction of Hg(II) complexed by reduced sulfur ligands in a sulfide-rich PZ, and (ii) enhanced sequestration of atmospheric Hg(0) to the sediments by thiols and sulfide that were enriched in the surface ocean as a result of PZE. This study thus demonstrates that Hg isotope compositions in ancient marine sedimentary rocks can be a promising proxy for PZE and therefore may provide valuable insights into changes in ocean chemistry and its impact on the evolution of life.}, } @article {pmid30275324, year = {2018}, author = {Sechet, E and Telford, E and Bonamy, C and Sansonetti, PJ and Sperandio, B}, title = {Natural molecules induce and synergize to boost expression of the human antimicrobial peptide β-defensin-3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9869-E9878}, pmid = {30275324}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Anti-Infective Agents/*pharmacology ; Anti-Inflammatory Agents/pharmacology ; Bacteria/*drug effects ; Biological Products/*pharmacology ; Cells, Cultured ; Chalcones/pharmacology ; Colon/cytology/drug effects/*metabolism ; Diterpenes/pharmacology ; Diterpenes, Kaurane/pharmacology ; Enzyme Inhibitors/pharmacology ; Epithelial Cells/cytology/drug effects/metabolism ; Gene Expression Regulation/*drug effects ; Humans ; Immunity, Innate/*drug effects ; beta-Defensins/*metabolism ; }, abstract = {Antimicrobial peptides (AMPs) are mucosal defense effectors of the human innate immune response. In the intestine, AMPs are produced and secreted by epithelial cells to protect the host against pathogens and to support homeostasis with commensals. The inducible nature of AMPs suggests that potent inducers could be used to increase their endogenous expression for the prevention or treatment of diseases. Here we aimed at identifying molecules from the natural pharmacopoeia that induce expression of human β-defensin-3 (HBD3), one of the most efficient AMPs, without modifying the production of proinflammatory cytokines. By screening, we identified three molecules isolated from medicinal plants, andrographolide, oridonin, and isoliquiritigenin, which induced HBD3 production in human colonic epithelial cells. This effect was observed without activation of the NF-κB pathway or the expression of associated proinflammatory cytokines. We identified the EGF receptor as the target of these compounds and characterized the downstream-activated MAPK pathways. At the chromatin level, molecules increased phosphorylation of histone H3 on serine S10 and recruitment of the c-Fos, c-Jun, and Elk1 or c-Myc transcription factors at the HBD3 promoter. Interestingly, stimulating cells with a combination of andrographolide and isoliquiritigenin synergistically enhanced HBD3 induction 10-fold more than observed with each molecule alone. Finally, we investigated the molecular basis governing the synergistic effect, confirmed our findings in human colonic primary cells, and demonstrated that synergism increased cellular antimicrobial activity. This work shows the capability of small molecules to achieve induction of epithelial antimicrobial defenses while simultaneously avoiding the deleterious risks of an inflammatory response.}, } @article {pmid30275323, year = {2018}, author = {Su, B and Huang, J and Fischer, T and Wang, Y and Kundzewicz, ZW and Zhai, J and Sun, H and Wang, A and Zeng, X and Wang, G and Tao, H and Gemmer, M and Li, X and Jiang, T}, title = {Drought losses in China might double between the 1.5 °C and 2.0 °C warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10600-10605}, pmid = {30275323}, issn = {1091-6490}, mesh = {China ; Droughts/prevention & control/*statistics & numerical data ; *Global Warming ; Humans ; *Models, Theoretical ; *Seasons ; Temperature ; Time Factors ; }, abstract = {We project drought losses in China under global temperature increase of 1.5 °C and 2.0 °C, based on the Standardized Precipitation Evapotranspiration Index (SPEI) and the Palmer Drought Severity Index (PDSI), a cluster analysis method, and "intensity-loss rate" function. In contrast to earlier studies, to project the drought losses, we predict the regional gross domestic product under shared socioeconomic pathways instead of using a static socioeconomic scenario. We identify increasing precipitation and evapotranspiration pattern for the 1.5 °C and 2.0 °C global warming above the preindustrial at 2020-2039 and 2040-2059, respectively. With increasing drought intensity and areal coverage across China, drought losses will soar. The estimated loss in a sustainable development pathway at the 1.5 °C warming level increases 10-fold in comparison with the reference period 1986-2005 and nearly threefold relative to the interval 2006-2015. However, limiting the temperature increase to 1.5 °C can reduce the annual drought losses in China by several tens of billions of US dollars, compared with the 2.0 °C warming.}, } @article {pmid30275322, year = {2018}, author = {Du, S and Pichoff, S and Kruse, K and Lutkenhaus, J}, title = {FtsZ filaments have the opposite kinetic polarity of microtubules.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10768-10773}, pmid = {30275322}, issn = {1091-6490}, support = {R01 GM029764/GM/NIGMS NIH HHS/United States ; R37 GM029764/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*metabolism ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Cytoskeletal Proteins/*chemistry/genetics/*metabolism ; Cytoskeleton/*metabolism ; Kinetics ; Microtubules/*chemistry/metabolism ; *Models, Statistical ; Mutation ; Polymerization ; Protein Conformation ; }, abstract = {FtsZ is the ancestral homolog of tubulin and assembles into the Z ring that organizes the division machinery to drive cell division in most bacteria. In contrast to tubulin that assembles into 13 stranded microtubules that undergo dynamic instability, FtsZ assembles into single-stranded filaments that treadmill to distribute the peptidoglycan synthetic machinery at the septum. Here, using longitudinal interface mutants of FtsZ, we demonstrate that the kinetic polarity of FtsZ filaments is opposite to that of microtubules. A conformational switch accompanying the assembly of FtsZ generates the kinetic polarity of FtsZ filaments, which explains the toxicity of interface mutants that function as a capper and reveals the mechanism of cooperative assembly. This approach can also be employed to determine the kinetic polarity of other filament-forming proteins.}, } @article {pmid30275321, year = {2018}, author = {Meyer, DE}, title = {From savannas to blue-phase LCD screens: Prospects and perils for child development in the Post-Modern Digital Information Age.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9845-9850}, pmid = {30275321}, issn = {1091-6490}, mesh = {Child ; *Child Development ; Child, Preschool ; Female ; Humans ; Infant ; *Information Technology ; Male ; *User-Computer Interface ; }, } @article {pmid30275320, year = {2018}, author = {Zhang, Y and Song, P and Chen, T and Liu, X and Chen, T and Wu, Z and Wang, Y and Xie, J and Xu, W}, title = {Unique size-dependent nanocatalysis revealed at the single atomically precise gold cluster level.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10588-10593}, pmid = {30275320}, issn = {1091-6490}, abstract = {Atomically precise metal clusters have attracted increasing interest owing to their unique size-dependent properties; however, little has been known about the effect of size on the catalytic properties of metal clusters at the single-cluster level. Here, by real-time monitoring with single-molecule fluorescence microscopy the size-dependent catalytic process of individual Au clusters at single-turnover resolution, we study the size-dependent catalytic behaviors of gold (Au) clusters at the single-cluster level, and then observe the strong size effect on the catalytic properties of individual Au clusters, in both catalytic product formation and dissociation processes. Surprisingly, indicated by both experiments and density functional theory (DFT) calculations, due to such a unique size effect, besides observing the different product dissociation behaviors on different-sized Au clusters, we also observe that small Au clusters [i.e., Au15(MPA)13; here, MPA denotes 3-mercaptopropionic acid] catalyze the product formation through a competitive Langmuir-Hinshelwood mechanism, while those relatively larger Au clusters [e.g., Au18(MPA)14 and Au25(MPA)18] or nanoparticles catalyze the same process through a noncompetitive Langmuir-Hinshelwood mechanism. Such a size effect on the nanocatalysis could be attributed intrinsically to the size-dependent electronic structure of Au clusters. Further analysis of dynamic activity fluctuation of Au clusters reveals more different catalytic properties between Au clusters and traditional Au nanoparticles due to their different size-dependent structures.}, } @article {pmid30275319, year = {2018}, author = {Christakis, DA and Ramirez, JSB and Ferguson, SM and Ravinder, S and Ramirez, JM}, title = {How early media exposure may affect cognitive function: A review of results from observations in humans and experiments in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9851-9858}, pmid = {30275319}, issn = {1091-6490}, mesh = {Animals ; *Attention Deficit Disorder with Hyperactivity/etiology/pathology/physiopathology ; Child ; Child, Preschool ; Disease Models, Animal ; Environmental Exposure/*adverse effects ; Humans ; Infant ; Mice ; }, abstract = {Attention deficit hyperactivity disorder (ADHD) is now among the most commonly diagnosed chronic psychological dysfunctions of childhood. By varying estimates, it has increased by 30% in the past 20 years. Environmental factors that might explain this increase have been explored. One such factor may be audiovisual media exposure during early childhood. Observational studies in humans have linked exposure to fast-paced television in the first 3 years of life with subsequent attentional deficits in later childhood. Although longitudinal and well controlled, the observational nature of these studies precludes definitive conclusions regarding a causal relationship. As experimental studies in humans are neither ethical nor practical, mouse models of excessive sensory stimulation (ESS) during childhood, akin to the enrichment studies that have previously shown benefits of stimulation in rodents, have been developed. Experimental studies using this model have corroborated that ESS leads to cognitive and behavioral deficits, some of which may be potentially detrimental. Given the ubiquity of media during childhood, these findings in humansand rodents perhaps have important implications for public health.}, } @article {pmid30275318, year = {2018}, author = {Beyens, I and Valkenburg, PM and Piotrowski, JT}, title = {Screen media use and ADHD-related behaviors: Four decades of research.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9875-9881}, pmid = {30275318}, issn = {1091-6490}, mesh = {Adolescent ; Age Factors ; Aggression/*psychology ; *Attention Deficit Disorder with Hyperactivity/physiopathology/psychology/therapy ; Child ; Child, Preschool ; Female ; Humans ; Male ; *Models, Psychological ; *Multimedia ; Sex Factors ; }, abstract = {The diagnosis of attention-deficit/hyperactivity disorder (ADHD) among children and adolescents has increased considerably over the past decades. Scholars and health professionals alike have expressed concern about the role of screen media in the rise in ADHD diagnosis. However, the extent to which screen media use and ADHD are linked remains a point of debate. To understand the current state of the field and, ultimately, move the field forward, we provide a systematic review of the literature on the relationship between children and adolescents' screen media use and ADHD-related behaviors (i.e., attention problems, hyperactivity, and impulsivity). Using the Differential Susceptibility to Media effects Model as a theoretical lens, we systematically organize the existing literature, identify potential shortcomings in this literature, and provide directions for future research. The available evidence suggests a statistically small relationship between media and ADHD-related behaviors. Evidence also suggests that individual child differences, such as gender and trait aggression, may moderate this relationship. There is a clear need for future research that investigates causality, underlying mechanisms, and differential susceptibility to the effects of screen media use on ADHD-related behaviors. It is only through a richer empirical body that we will be able to fully understand the media-ADHD relationship.}, } @article {pmid30275317, year = {2018}, author = {Wu, K and Oberstein, A and Wang, W and Shenk, T}, title = {Role of PDGF receptor-α during human cytomegalovirus entry into fibroblasts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9889-E9898}, pmid = {30275317}, issn = {1091-6490}, support = {F32 AI106175/AI/NIAID NIH HHS/United States ; R01 AI112951/AI/NIAID NIH HHS/United States ; }, mesh = {Cells, Cultured ; Cytomegalovirus/*physiology ; Cytomegalovirus Infections/metabolism/*virology ; Fibroblasts/cytology/metabolism/*virology ; Humans ; Lung/cytology/metabolism/*virology ; Receptor, Platelet-Derived Growth Factor alpha/*metabolism ; Viral Envelope Proteins/metabolism ; *Virion ; *Virus Internalization ; }, abstract = {Human CMV (HCMV) exhibits a broad cell tropism that depends on two virion glycoprotein complexes: a trimeric complex (gH/gL/gO) that facilitates viral infection primarily in fibroblasts and a pentameric complex (gH/gL/pUL128-pUL130-pUL131A) that mediates infection in epithelial and endothelial cells. We performed genome-wide CRISPR screens in which the PDGF receptor-α (PDGFRα) was identified as the most significant cellular gene product essential for infection by HCMV virions containing only trimeric complex (trimer-only virus). Trimer-only virus did not enter PDGFRα knockout fibroblasts. By using knockout fibroblasts, the extracellular domain of PDGFRα required for virus entry was mapped, and the intracellular tyrosine kinase domain was shown to be nonessential. In addition, direct cell-to-cell spread of virus from knockout cells transfected with trimer-only viral DNA was blocked, despite the production of infectious virus in the transfected cells. In contrast to trimer-only virus, wild-type HCMV virions containing both trimeric and pentameric complexes entered PDGFRα knockout cells, reinforcing the view that fibroblasts contain a second, independent receptor for the pentameric complex. Importantly, however, wild-type virus entered the knockout fibroblasts at reduced efficiency compared with parental fibroblasts, arguing that the cellular receptor for the virion pentameric complex is limiting or that virions are produced containing different relative amounts of the two glycoprotein complexes. Finally, ectopic expression of PDGFRα in ARPE-19 epithelial cells and THP-1 monocytic cells, which have little to no endogenous PDGFRα expression, markedly enhanced their susceptibility to trimer-only virions. In sum, our data clarify several key determinants of HCMV tropism.}, } @article {pmid30275316, year = {2018}, author = {Secor, PR and Michaels, LA and Ratjen, A and Jennings, LK and Singh, PK}, title = {Entropically driven aggregation of bacteria by host polymers promotes antibiotic tolerance in Pseudomonas aeruginosa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10780-10785}, pmid = {30275316}, issn = {1091-6490}, support = {K22 AI125282/AI/NIAID NIH HHS/United States ; K24 HL102246/HL/NHLBI NIH HHS/United States ; P20 GM103546/GM/NIGMS NIH HHS/United States ; R01 AI101307/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Biofilms ; *Drug Tolerance ; *Entropy ; Humans ; Microbial Sensitivity Tests ; Phenotype ; Pseudomonas Infections/*drug therapy/*microbiology ; Pseudomonas aeruginosa/*chemistry/*drug effects/isolation & purification ; }, abstract = {Bacteria causing chronic infections are generally observed living in cell aggregates suspended in polymer-rich host secretions, and bacterial phenotypes induced by aggregated growth may be key factors in chronic infection pathogenesis. Bacterial aggregation is commonly thought of as a consequence of biofilm formation; however the mechanisms producing aggregation in vivo remain unclear. Here we show that polymers that are abundant at chronic infection sites cause bacteria to aggregate by the depletion aggregation mechanism, which does not require biofilm formation functions. Depletion aggregation is mediated by entropic forces between uncharged or like-charged polymers and particles (e.g., bacteria). Our experiments also indicate that depletion aggregation of bacteria induces marked antibiotic tolerance that was dependent on the SOS response, a stress response activated by genotoxic stress. These findings raise the possibility that targeting conditions that promote depletion aggregation or mechanisms of depletion-mediated tolerance could lead to new therapeutic approaches to combat chronic bacterial infections.}, } @article {pmid30275315, year = {2018}, author = {Katz, B and Shah, P and Meyer, DE}, title = {How to play 20 questions with nature and lose: Reflections on 100 years of brain-training research.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9897-9904}, pmid = {30275315}, issn = {1091-6490}, mesh = {Animals ; Behavioral Research/*history/methods/*trends ; *Cognition ; History, 20th Century ; History, 21st Century ; Humans ; }, abstract = {Despite dozens of empirical studies and a growing body of meta-analytic work, there is little consensus regarding the efficacy of cognitive training. In this review, we examine why this substantial corpus has failed to answer the often-asked question, "Does cognitive training work?" We first define cognitive training and discuss the general principles underlying training interventions. Next, we review historical interventions and discuss how findings from this early work remain highly relevant for current cognitive-training research. We highlight a variety of issues preventing real progress in understanding the underlying mechanisms of training, including the lack of a coherent theoretical framework to guide training research and methodological issues across studies and meta-analyses. Finally, suggestions for correcting these issues are offered in the hope that we might make greater progress in the next 100 y of cognitive-training research.}, } @article {pmid30275314, year = {2018}, author = {Wang, XT and Cohen, AL and Luu, V and Ren, H and Su, Z and Haug, GH and Sigman, DM}, title = {Natural forcing of the North Atlantic nitrogen cycle in the Anthropocene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10606-10611}, pmid = {30275314}, issn = {1091-6490}, mesh = {Atlantic Ocean ; Atmosphere ; *Coral Reefs ; *Ecosystem ; Human Activities ; Humans ; Nitrogen/*analysis ; *Nitrogen Cycle ; North America ; Seawater/*analysis ; Temperature ; }, abstract = {Human alteration of the global nitrogen cycle intensified over the 1900s. Model simulations suggest that large swaths of the open ocean, including the North Atlantic and the western Pacific, have already been affected by anthropogenic nitrogen through atmospheric transport and deposition. Here we report an ∼130-year-long record of the 15N/14N of skeleton-bound organic matter in a coral from the outer reef of Bermuda, which provides a test of the hypothesis that anthropogenic atmospheric nitrogen has significantly augmented the nitrogen supply to the open North Atlantic surface ocean. The Bermuda 15N/14N record does not show a long-term decline in the Anthropocene of the amplitude predicted by model simulations or observed in a western Pacific coral 15N/14N record. Rather, the decadal variations in the Bermuda 15N/14N record appear to be driven by the North Atlantic Oscillation, most likely through changes in the formation rate of Subtropical Mode Water. Given that anthropogenic nitrogen emissions have been decreasing in North America since the 1990s, this study suggests that in the coming decades, the open North Atlantic will remain minimally affected by anthropogenic nitrogen deposition.}, } @article {pmid30275313, year = {2018}, author = {de Wit, M and George, GM and Ince, YÇ and Dankwa-Egli, B and Hersch, M and Zeeman, SC and Fankhauser, C}, title = {Changes in resource partitioning between and within organs support growth adjustment to neighbor proximity in Brassicaceae seedlings.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9953-E9961}, pmid = {30275313}, issn = {1091-6490}, mesh = {Arabidopsis/*growth & development/metabolism ; Brassicaceae/*growth & development/metabolism ; Carbon/*metabolism ; Cotyledon/*growth & development/metabolism ; Hypocotyl/*growth & development/metabolism ; Light ; Phytochrome ; Plant Leaves/*growth & development/metabolism ; Seedlings/*growth & development/metabolism ; Signal Transduction ; }, abstract = {In shade-intolerant plants, the perception of proximate neighbors rapidly induces architectural changes resulting in elongated stems and reduced leaf size. Sensing and signaling steps triggering this modified growth program have been identified. However, the underlying changes in resource allocation that fuel stem growth remain poorly understood. Through 14CO2 pulse labeling of Brassica rapa seedlings, we show that perception of the neighbor detection signal, low ratio of red to far-red light (R:FR), leads to increased carbon allocation from the major site of photosynthesis (cotyledons) to the elongating hypocotyl. While carbon fixation and metabolite levels remain similar in low R:FR, partitioning to all downstream carbon pools within the hypocotyl is increased. Genetic analyses using Arabidopsis thaliana mutants indicate that low-R:FR-induced hypocotyl elongation requires sucrose transport from the cotyledons and is regulated by a PIF7-dependent metabolic response. Moreover, our data suggest that starch metabolism in the hypocotyl has a growth-regulatory function. The results reveal a key mechanism by which metabolic adjustments can support rapid growth adaptation to a changing environment.}, } @article {pmid30275312, year = {2018}, author = {Uncapher, MR and Wagner, AD}, title = {Minds and brains of media multitaskers: Current findings and future directions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9889-9896}, pmid = {30275312}, issn = {1091-6490}, support = {R21 MH099812/MH/NIMH NIH HHS/United States ; R56 MH111672/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/*physiology ; Cognition/*physiology ; Female ; Humans ; Male ; *Multimedia ; }, abstract = {Media and technology are ubiquitous elements of our daily lives, and their use can offer many benefits and rewards. At the same time, decisions about how individuals structure their use of media can be informed by consideration of whether, and if so how, the mind and brain are shaped by different use patterns. Here we review the growing body of research that investigates the cognitive and neural profiles of individuals who differ in the extent to which they simultaneously engage with multiple media streams, or ‟media multitasking." While the literature is still sparse, and is marked by both convergent and divergent findings, the balance of evidence suggests that heavier media multitaskers exhibit poorer performance in a number of cognitive domains, relative to lighter media multitaskers (although many studies find no performance differences between groups). When evidence points to a relationship between media multitasking level and cognition, it is often on tasks that require or are influenced by fluctuations in sustained goal-directed attention. Given the real-world significance of such findings, further research is needed to uncover the mechanistic underpinnings of observed differences, to determine the direction of causality, to understand whether remediation efforts are needed and effective, and to determine how measurement heterogeneity relates to variable outcomes. Such efforts will ultimately inform decisions about how to minimize the potential costs and maximize the many benefits of our ever-evolving media landscape.}, } @article {pmid30275311, year = {2018}, author = {Huang, WH and Wang, DC and Allen, WE and Klope, M and Hu, H and Shamloo, M and Luo, L}, title = {Early adolescent Rai1 reactivation reverses transcriptional and social interaction deficits in a mouse model of Smith-Magenis syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10744-10749}, pmid = {30275311}, issn = {1091-6490}, support = {K99 HD092545/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Animals ; Dendritic Spines/metabolism/pathology ; *Disease Models, Animal ; *Haploinsufficiency ; Heterozygote ; Humans ; *Interpersonal Relations ; Male ; Mice ; Mutation ; Phenotype ; Smith-Magenis Syndrome/*genetics/pathology ; Social Behavior Disorders/genetics/*prevention & control ; Trans-Activators/*pharmacology ; }, abstract = {Haploinsufficiency of Retinoic Acid Induced 1 (RAI1) causes Smith-Magenis syndrome (SMS), a syndromic autism spectrum disorder associated with craniofacial abnormalities, intellectual disability, and behavioral problems. There is currently no cure for SMS. Here, we generated a genetic mouse model to determine the reversibility of SMS-like neurobehavioral phenotypes in Rai1 heterozygous mice. We show that normalizing the Rai1 level 3-4 wk after birth corrected the expression of genes related to neural developmental pathways and fully reversed a social interaction deficit caused by Rai1 haploinsufficiency. In contrast, Rai1 reactivation 7-8 wk after birth was not beneficial. We also demonstrated that the correct Rai1 dose is required in both excitatory and inhibitory neurons for proper social interactions. Finally, we found that Rai1 heterozygous mice exhibited a reduction of dendritic spines in the medial prefrontal cortex (mPFC) and that optogenetic activation of mPFC neurons in adults improved the social interaction deficit of Rai1 heterozygous mice. Together, these results suggest the existence of a postnatal temporal window during which restoring Rai1 can improve the transcriptional and social behavioral deficits in a mouse model of SMS. It is possible that circuit-level interventions would be beneficial beyond this critical window.}, } @article {pmid30275310, year = {2018}, author = {Grimaldi, C and Marcy, GW}, title = {Bayesian approach to SETI.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9755-E9764}, pmid = {30275310}, issn = {1091-6490}, abstract = {The search for technosignatures from hypothetical galactic civilizations is going through a new phase of intense activity. For the first time, a significant fraction of the vast search space is expected to be sampled in the foreseeable future, potentially bringing informative data about the abundance of detectable extraterrestrial civilizations or the lack thereof. Starting from the current state of ignorance about the galactic population of nonnatural electromagnetic signals, we formulate a Bayesian statistical model to infer the mean number of radio signals crossing Earth, assuming either nondetection or the detection of signals in future surveys of the Galaxy. Under fairly noninformative priors, we find that not detecting signals within about 1 kly from Earth, while suggesting the lack of galactic emitters or at best the scarcity thereof, is nonetheless still consistent with a probability exceeding 10% that typically over [Formula: see text] signals could be crossing Earth, with radiated power analogous to that of the Arecibo radar, but coming from farther in the Milky Way. The existence in the Galaxy of potentially detectable Arecibo-like emitters can be reasonably ruled out only if all-sky surveys detect no such signals up to a radius of about 40 kly, an endeavor requiring detector sensitivities thousands times higher than those of current telescopes. Conversely, finding even one Arecibo-like signal within [Formula: see text] light years, a possibility within reach of current detectors, implies almost certainly that typically more than [Formula: see text] signals of comparable radiated power cross the Earth, yet to be discovered.}, } @article {pmid30275309, year = {2018}, author = {Darby, RR and Joutsa, J and Burke, MJ and Fox, MD}, title = {Lesion network localization of free will.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10792-10797}, pmid = {30275309}, issn = {1091-6490}, support = {K23 NS083741/NS/NINDS NIH HHS/United States ; R01 MH113929/MH/NIMH NIH HHS/United States ; }, mesh = {Brain/*pathology ; Brain Diseases/*pathology ; Brain Mapping ; Gyrus Cinguli/*pathology ; Humans ; *Neural Pathways ; Neuroimaging ; *Personal Autonomy ; *Volition ; }, abstract = {Our perception of free will is composed of a desire to act (volition) and a sense of responsibility for our actions (agency). Brain damage can disrupt these processes, but which regions are most important for free will perception remains unclear. Here, we study focal brain lesions that disrupt volition, causing akinetic mutism (n = 28), or disrupt agency, causing alien limb syndrome (n = 50), to better localize these processes in the human brain. Lesion locations causing either syndrome were highly heterogeneous, occurring in a variety of different brain locations. We next used a recently validated technique termed lesion network mapping to determine whether these heterogeneous lesion locations localized to specific brain networks. Lesion locations causing akinetic mutism all fell within one network, defined by connectivity to the anterior cingulate cortex. Lesion locations causing alien limb fell within a separate network, defined by connectivity to the precuneus. Both findings were specific for these syndromes compared with brain lesions causing similar physical impairments but without disordered free will. Finally, our lesion-based localization matched network localization for brain stimulation locations that disrupt free will and neuroimaging abnormalities in patients with psychiatric disorders of free will without overt brain lesions. Collectively, our results demonstrate that lesions in different locations causing disordered volition and agency localize to unique brain networks, lending insight into the neuroanatomical substrate of free will perception.}, } @article {pmid30275308, year = {2018}, author = {Weng, PJ and Gao, Y and Gregory, MT and Wang, P and Wang, Y and Yang, W}, title = {Bypassing a 8,5'-cyclo-2'-deoxyadenosine lesion by human DNA polymerase η at atomic resolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10660-10665}, pmid = {30275308}, issn = {1091-6490}, support = {R01 CA210072/CA/NCI NIH HHS/United States ; }, mesh = {Base Pairing ; Calcium/chemistry/metabolism ; Crystallography, X-Ray ; *DNA Damage ; DNA Repair ; DNA Replication ; DNA-Directed DNA Polymerase/*chemistry/*metabolism ; Deoxyadenosines/*toxicity ; Humans ; Magnesium/chemistry/metabolism ; Manganese/chemistry/metabolism ; Models, Molecular ; Mutagens ; Nucleotides/chemistry/*metabolism ; Protein Conformation ; }, abstract = {Oxidatively induced DNA lesions 8,5'-cyclopurine-2'-deoxynucleosides (cdPus) are prevalent and cytotoxic by impeding DNA replication and transcription. Both the 5'R- and 5'S-diastereomers of cdPu can be removed by nucleotide excision repair; however, the 5'S-cdPu is more resistant to repair than the 5'R counterpart. Here, we report the crystal structures of human polymerase (Pol) η bypassing 5'S-8,5'-cyclo-2'-deoxyadenosine (cdA) in insertion and the following two extension steps. The cdA-containing DNA structures vary in response to the protein environment. Supported by the "molecular splint" of Pol η, the structure of 5'S-cdA at 1.75-Å resolution reveals that the backbone is pinched toward the minor groove and the adenine base is tilted. In the templating position, the cdA takes up the extra space usually reserved for the thymine dimer, and dTTP is efficiently incorporated by Pol η in the presence of Mn2+ Rigid distortions of the DNA duplex by cdA, however, prevent normal base pairing and hinder immediate primer extension by Pol η. Our results provide structural insights into the strong replication blockage effect and the mutagenic property of the cdPu lesions in cells.}, } @article {pmid30275307, year = {2018}, author = {Liu, J and Wu, X and Yao, X and Yu, R and Larkin, PJ and Liu, CM}, title = {Mutations in the DNA demethylase OsROS1 result in a thickened aleurone and improved nutritional value in rice grains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11327-11332}, pmid = {30275307}, issn = {1091-6490}, mesh = {Alleles ; DNA/*genetics ; DNA Methylation/*genetics ; Endosperm/genetics ; Gene Expression Regulation, Plant/genetics ; Introns/genetics ; Mutation/*genetics ; Nutritive Value/*genetics ; Oryza/*genetics ; Phenotype ; Plant Proteins/*genetics ; Seeds/genetics ; Starch/genetics ; Transcription Factors/genetics ; }, abstract = {The rice endosperm, consisting of an outer single-cell layer aleurone and an inner starchy endosperm, is an important staple food for humans. While starchy endosperm stores mainly starch, the aleurone is rich in an array of proteins, vitamins, and minerals. To improve the nutritional value of rice, we screened for mutants with thickened aleurones using a half-seed assay and identified thick aleurone 2-1 (ta2-1), in which the aleurone has 4.8 ± 2.2 cell layers on average. Except for starch, the contents of all measured nutritional factors, including lipids, proteins, vitamins, minerals, and dietary fibers, were increased in ta2-1 grains. Map-based cloning showed that TA2 encodes the DNA demethylase OsROS1. A point mutation in the 14th intron of OsROS1 led to alternative splicing that generated an extra transcript, mOsROS1, with a 21-nt insertion from the intron. Genetic analyses showed that the ta2-1 phenotype is inherited with an unusual gametophytic maternal effect, which is caused not by imprinted gene expression but rather by the presence of the mOsROS1 transcript. Five additional ta2 alleles with the increased aleurone cell layer and different inheritance patterns were identified by TILLING. Genome-wide bisulfite sequencing revealed general increases in CG and CHG methylations in ta2-1 endosperms, along with hypermethylation and reduced expression in two putative aleurone differentiation-related transcription factors. This study thus suggests that OsROS1-mediated DNA demethylation restricts the number of aleurone cell layers in rice and provides a way to improve the nutrition of rice.}, } @article {pmid30275306, year = {2018}, author = {Prescott, AT and Sargent, JD and Hull, JG}, title = {Metaanalysis of the relationship between violent video game play and physical aggression over time.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9882-9888}, pmid = {30275306}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Aggression/*psychology ; Child ; Female ; Humans ; Male ; *Models, Psychological ; Time Factors ; Video Games/*adverse effects ; Violence/*psychology ; }, abstract = {To clarify and quantify the influence of video game violence (VGV) on aggressive behavior, we conducted a metaanalysis of all prospective studies to date that assessed the relation between exposure to VGV and subsequent overt physical aggression. The search strategy identified 24 studies with over 17,000 participants and time lags ranging from 3 months to 4 years. The samples comprised various nationalities and ethnicities with mean ages from 9 to 19 years. For each study we obtained the standardized regression coefficient for the prospective effect of VGV on subsequent aggression, controlling for baseline aggression. VGV was related to aggression using both fixed [β = 0.113, 95% CI = (0.098, 0.128)] and random effects models [β = 0.106 (0.078, 0.134)]. When all available covariates were included, the size of the effect remained significant for both models [β = 0.080 (0.065, 0.094) and β = 0.078 (0.053, 0.102), respectively]. No evidence of publication bias was found. Ethnicity was a statistically significant moderator for the fixed-effects models (P ≤ 0.011) but not for the random-effects models. Stratified analyses indicated the effect was largest among Whites, intermediate among Asians, and nonsignificant among Hispanics. Discussion focuses on the implications of such findings for current debates regarding the effects of violent video games on physical aggression.}, } @article {pmid30275305, year = {2018}, author = {}, title = {Correction to Supporting Information for Reid-Bayliss and Loeb, Accurate RNA consensus sequencing for high-fidelity detection of transcriptional mutagenesis-induced epimutations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9754}, doi = {10.1073/pnas.1815350115}, pmid = {30275305}, issn = {1091-6490}, } @article {pmid30275304, year = {2018}, author = {Parent, B and Leclere, M and Lacube, S and Semenov, MA and Welcker, C and Martre, P and Tardieu, F}, title = {Maize yields over Europe may increase in spite of climate change, with an appropriate use of the genetic variability of flowering time.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10642-10647}, pmid = {30275304}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; Agriculture/*methods/trends ; *Climate Change ; Crops, Agricultural/*growth & development ; Europe ; Flowers/*growth & development ; Time Factors ; Zea mays/*growth & development ; }, abstract = {Projections based on invariant genotypes and agronomic practices indicate that climate change will largely decrease crop yields. The comparatively few studies considering farmers' adaptation result in a diversity of impacts depending on their assumptions. We combined experiments and process-based modeling for analyzing the consequences of climate change on European maize yields if farmers made the best use of the current genetic variability of cycle duration, based on practices they currently use. We first showed that the genetic variability of maize flowering time is sufficient for identifying a cycle duration that maximizes yield in a range of European climatic conditions. This was observed in six field experiments with a panel of 121 accessions and extended to 59 European sites over 36 years with a crop model. The assumption that farmers use optimal cycle duration and sowing date was supported by comparison with historical data. Simulations were then carried out for 2050 with 3 million combinations of crop cycle durations, climate scenarios, management practices, and modeling hypotheses. Simulated grain production over Europe in 2050 was stable (-1 to +1%) compared with the 1975-2010 baseline period under the hypotheses of unchanged cycle duration, whereas it was increased (+4-7%) when crop cycle duration and sowing dates were optimized in each local environment. The combined effects of climate change and farmer adaptation reduced the yield gradient between south and north of Europe and increased European maize production if farmers continued to make the best use of the genetic variability of crop cycle duration.}, } @article {pmid30275303, year = {2018}, author = {Kirkorian, HL and Anderson, DR}, title = {Effect of sequential video shot comprehensibility on attentional synchrony: A comparison of children and adults.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9867-9874}, pmid = {30275303}, issn = {1091-6490}, mesh = {Adult ; Attention/*physiology ; Child, Preschool ; Comprehension/*physiology ; Female ; Fixation, Ocular/*physiology ; Humans ; Male ; *Multimedia ; }, abstract = {To comprehend edited video, viewers must infer the meaning conveyed by successive video shots (i.e., continuous video segments separated by edit points, such as camera cuts). The central question here was whether comprehension-related top-down cognitive processes drive eye movements during sequential processing of video montage. Eye movements were recorded as 4 year olds and adults (n = 62) watched a video with the same constituent shots in either normal or random sequence. The key analyses compared eye movements to constituent shots when presented in normal order with those to the same shots presented in random order. The dependent variable was attentional synchrony or the extent to which viewers looked at the same location at the same time, indicating commonality of processing the video. This was calculated as the bivariate contour ellipse area within which points of gaze fell during each video frame. Results indicated that children were more scattered in their gaze locations than adults. Viewers became more similar to each other as normal vignettes unfolded over time; this was especially true in adults and possibly reflects a growing and shared understanding of the content. Conversely, adult attentional synchrony was reduced when watching random shot sequences. Thus, attentional synchrony during normal video viewing is driven not only by salient visual features, such as movement and areas of high contrast, but also, by the unfolding sequential comprehension of video montage, especially in adults. Differences between children and adults indicate that this top-down control of eye movements while watching video changes systematically over development.}, } @article {pmid30275302, year = {2018}, author = {Kumar, S and Suman, S and Fornace, AJ and Datta, K}, title = {Space radiation triggers persistent stress response, increases senescent signaling, and decreases cell migration in mouse intestine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9832-E9841}, pmid = {30275302}, issn = {1091-6490}, support = {P30 CA051008/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Movement/*radiation effects ; Cellular Senescence/*radiation effects ; Epithelial Cells/*radiation effects ; Gamma Rays/*adverse effects ; Intestines/*pathology/radiation effects ; Iron Radioisotopes/adverse effects ; Male ; Mice ; Mice, Inbred C57BL ; Signal Transduction/radiation effects ; Stress, Physiological/*radiation effects ; Whole-Body Irradiation/*adverse effects ; }, abstract = {Proliferative gastrointestinal (GI) tissue is radiation-sensitive, and heavy-ion space radiation with its high-linear energy transfer (high-LET) and higher damaging potential than low-LET γ-rays is predicted to compromise astronauts' GI function. However, much uncertainty remains in our understanding of how heavy ions affect coordinated epithelial cell migration and extrusion, which are essential for GI homeostasis. Here we show using mouse small intestine as a model and BrdU pulse labeling that cell migration along the crypt-villus axis is persistently decreased after a low dose of heavy-ion 56Fe radiation relative to control and γ-rays. Wnt/β-catenin and its downstream EphrinB/EphB signaling are key to intestinal epithelial cell (IEC) proliferation and positioning during migration, and both are up-regulated after 56Fe radiation. Conversely, factors involved in cell polarity and adhesion and cell-extracellular matrix interactions were persistently down-regulated after 56Fe irradiation-potentially altering cytoskeletal remodeling and cell extrusion. 56Fe radiation triggered a time-dependent increase in γH2AX foci and senescent cells but without a noticeable increase in apoptosis. Some senescent cells acquired the senescence-associated secretory phenotype, and this was accompanied by increased IEC proliferation, implying a role for progrowth inflammatory factors. Collectively, this study demonstrates a unique phenomenon of heavy-ion radiation-induced persistently delayed IEC migration involving chronic sublethal genotoxic and oncogenic stress-induced altered cytoskeletal dynamics, which were seen even a year later. When considered along with changes in barrier function and nutrient absorption factors as well as increased intestinal tumorigenesis, our in vivo data raise a serious concern for long-duration deep-space manned missions.}, } @article {pmid30275301, year = {2018}, author = {Chen, M and Fredrick, K}, title = {Measures of single- versus multiple-round translation argue against a mechanism to ensure coupling of transcription and translation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10774-10779}, pmid = {30275301}, issn = {1091-6490}, support = {R01 GM072528/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA-Directed RNA Polymerases/chemistry/genetics/*metabolism ; Escherichia coli/growth & development/*metabolism ; Models, Molecular ; Mutation ; *Protein Biosynthesis ; Protein Conformation ; Ribosomes/*metabolism ; *Transcription, Genetic ; }, abstract = {In prokaryotes, the synthesis of RNA and protein occurs simultaneously in the cytoplasm. A number of studies indicate that translation can strongly impact transcription, a phenomenon often attributed to physical coupling between RNA polymerase (RNAP) and the lead ribosome on the nascent mRNA. Whether there generally exists a mechanism to ensure or promote RNAP-ribosome coupling remains unclear. Here, we used an efficient hammerhead ribozyme and developed a reporter system to measure single- versus multiple-round translation in Escherichia coli Six pairs of cotranscribed and differentially translated genes were analyzed. For five of them, the stoichiometry of the two protein products came no closer to unity (1:1) when the rounds of translation were severely reduced in wild-type cells. Introduction of mutation rpoB(I572N), which slows RNAP elongation, could promote coupling, as indicated by stoichiometric SspA and SspB products in the single-round assay. These data are consistent with models of stochastic coupling in which the probability of coupling depends on the relative rates of transcription and translation and suggest that RNAP often transcribes without a linked ribosome.}, } @article {pmid30275300, year = {2018}, author = {Karney-Grobe, S and Russo, A and Frey, E and Milbrandt, J and DiAntonio, A}, title = {HSP90 is a chaperone for DLK and is required for axon injury signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9899-E9908}, pmid = {30275300}, issn = {1091-6490}, support = {F32 NS093962/NS/NINDS NIH HHS/United States ; F31 NS101827/NS/NINDS NIH HHS/United States ; R21 NS087562/NS/NINDS NIH HHS/United States ; R01 NS065053/NS/NINDS NIH HHS/United States ; R33 NS087562/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Axons/*physiology ; Cells, Cultured ; Drosophila/genetics/growth & development/metabolism ; Female ; HSP90 Heat-Shock Proteins/genetics/*metabolism ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Male ; Mice ; *Nerve Regeneration ; Neurites/*physiology ; Neurons/cytology/*physiology ; Presynaptic Terminals/*physiology ; }, abstract = {Peripheral nerve injury induces a robust proregenerative program that drives axon regeneration. While many regeneration-associated genes are known, the mechanisms by which injury activates them are less well-understood. To identify such mechanisms, we performed a loss-of-function pharmacological screen in cultured adult mouse sensory neurons for proteins required to activate this program. Well-characterized inhibitors were present as injury signaling was induced but were removed before axon outgrowth to identify molecules that block induction of the program. Of 480 compounds, 35 prevented injury-induced neurite regrowth. The top hits were inhibitors to heat shock protein 90 (HSP90), a chaperone with no known role in axon injury. HSP90 inhibition blocks injury-induced activation of the proregenerative transcription factor cJun and several regeneration-associated genes. These phenotypes mimic loss of the proregenerative kinase, dual leucine zipper kinase (DLK), a critical neuronal stress sensor that drives axon degeneration, axon regeneration, and cell death. HSP90 is an atypical chaperone that promotes the stability of signaling molecules. HSP90 and DLK show two hallmarks of HSP90-client relationships: (i) HSP90 binds DLK, and (ii) HSP90 inhibition leads to rapid degradation of existing DLK protein. Moreover, HSP90 is required for DLK stability in vivo, where HSP90 inhibitor reduces DLK protein in the sciatic nerve. This phenomenon is evolutionarily conserved in Drosophila Genetic knockdown of Drosophila HSP90, Hsp83, decreases levels of Drosophila DLK, Wallenda, and blocks Wallenda-dependent synaptic terminal overgrowth and injury signaling. Our findings support the hypothesis that HSP90 chaperones DLK and is required for DLK functions, including proregenerative axon injury signaling.}, } @article {pmid30275299, year = {2018}, author = {Stokes, EC and Seto, KC}, title = {Tradeoffs in environmental and equity gains from job accessibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9773-E9781}, pmid = {30275299}, issn = {1091-6490}, abstract = {Increasing job accessibility is considered key to urban sustainability progress, both from an environmental and from a social perspective. However, sustainability outcomes depend on the processes contributing to accessibility trends, not just the trends themselves. Here, we ask whether sustainability benefits have followed from accessibility trends in the United States. We measure changes in accessibility from 2002 to 2014 across 909 US urban areas and decompose these changes to understand underlying infrastructure and land use processes. Our results show that job accessibility has increased across 74% of urban areas for the average resident, using both cars and transit. However, most of these accessibility gains were not achieved in ways that are inherently beneficial to environmental or social sustainability. In some urban areas, accessibility increases were conducive to reducing emissions, while in others, accessibility increases were conducive to reducing social inequities. However, accessibility increases almost never created a simultaneous social and environmental "win-win," as is often assumed. Our findings highlight how the spatial patterns of urbanization create tradeoffs between different facets of sustainability. Identifying where social objectives take precedence over environmental objectives (or vice versa) could help determine how accessibility increases can be accomplished to contribute to a more sustainable urban future.}, } @article {pmid30275298, year = {2018}, author = {Lytle, SR and Garcia-Sierra, A and Kuhl, PK}, title = {Two are better than one: Infant language learning from video improves in the presence of peers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9859-9866}, pmid = {30275298}, issn = {1091-6490}, mesh = {*Computer Terminals ; Female ; Humans ; Infant ; Learning/*physiology ; Male ; *Multimedia ; }, abstract = {Studies show that young children learn new phonemes and words from humans significantly better than from machines. However, it is not clear why learning from video is ineffective or what might be done to improve learning from a screen. The present study, conducted with 9-month-old infants, utilized a manipulation-touch screen video-which allowed infants to control presentations of foreign-language video clips. We tested the hypothesis that infant learning from a screen would be enhanced in the presence of a peer, as opposed to learning alone. Brain measures of phonetic learning and detailed analyses of interaction during learning confirm the hypothesis that social partners enhance learning, even from screens.}, } @article {pmid30275297, year = {2018}, author = {Peters, K and Pazos, M and Edoo, Z and Hugonnet, JE and Martorana, AM and Polissi, A and VanNieuwenhze, MS and Arthur, M and Vollmer, W}, title = {Copper inhibits peptidoglycan LD-transpeptidases suppressing β-lactam resistance due to bypass of penicillin-binding proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10786-10791}, pmid = {30275297}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 GM113172/GM/NIGMS NIH HHS/United States ; 101824/Z/13/Z//Wellcome Trust/United Kingdom ; MR/N002679/1//Medical Research Council/United Kingdom ; }, mesh = {Aminoacyltransferases/*antagonists & inhibitors ; Anti-Bacterial Agents/pharmacology ; Cell Wall/chemistry/metabolism ; Copper/*pharmacology ; Enterococcus faecium/drug effects/*enzymology ; Escherichia coli/drug effects/*enzymology ; Microbial Sensitivity Tests ; Penicillin-Binding Proteins/*metabolism ; Peptidoglycan/*metabolism ; Substrate Specificity ; Trace Elements/pharmacology ; beta-Lactam Resistance/*drug effects ; beta-Lactams/pharmacology ; }, abstract = {The peptidoglycan (PG) layer stabilizes the bacterial cell envelope to maintain the integrity and shape of the cell. Penicillin-binding proteins (PBPs) synthesize essential 4-3 cross-links in PG and are inhibited by β-lactam antibiotics. Some clinical isolates and laboratory strains of Enterococcus faecium and Escherichia coli achieve high-level β-lactam resistance by utilizing β-lactam-insensitive LD-transpeptidases (LDTs) to produce exclusively 3-3 cross-links in PG, bypassing the PBPs. In E. coli, other LDTs covalently attach the lipoprotein Lpp to PG to stabilize the envelope and maintain the permeability barrier function of the outermembrane. Here we show that subminimal inhibitory concentration of copper chloride sensitizes E. coli cells to sodium dodecyl sulfate and impair survival upon LPS transport stress, indicating reduced cell envelope robustness. Cells grown in the presence of copper chloride lacked 3-3 cross-links in PG and displayed reduced covalent attachment of Braun's lipoprotein and reduced incorporation of a fluorescent d-amino acid, suggesting inhibition of LDTs. Copper dramatically decreased the minimal inhibitory concentration of ampicillin in E. coli and E. faecium strains with a resistance mechanism relying on LDTs and inhibited purified LDTs at submillimolar concentrations. Hence, our work reveals how copper affects bacterial cell envelope stability and counteracts LDT-mediated β-lactam resistance.}, } @article {pmid30275296, year = {2018}, author = {Obata-Ninomiya, K and Ishiwata, K and Nakano, H and Endo, Y and Ichikawa, T and Onodera, A and Hirahara, K and Okamoto, Y and Kanuka, H and Nakayama, T}, title = {CXCR6+ST2+ memory T helper 2 cells induced the expression of major basic protein in eosinophils to reduce the fecundity of helminth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9849-E9858}, pmid = {30275296}, issn = {1091-6490}, mesh = {Animals ; Eosinophils/*immunology/metabolism/parasitology ; Fertility/*immunology/physiology ; Immunologic Memory/*immunology ; Inflammation/immunology/metabolism/prevention & control ; Interleukin-1 Receptor-Like 1 Protein/*metabolism ; Lung/immunology/metabolism/parasitology ; Mice ; Mice, Inbred BALB C ; Myelin Basic Protein/*metabolism ; Nippostrongylus/*immunology ; Receptors, CXCR6/*metabolism ; Receptors, Interleukin/metabolism ; Strongylida Infections/complications/parasitology ; T-Lymphocytes, Regulatory/immunology ; Th1 Cells/immunology/metabolism ; Th2 Cells/*immunology/metabolism ; }, abstract = {Memory T helper (mTh) cells play important roles in the reinfection of pathogens and drive the pathogenesis of diseases. While recent studies have characterized the pathogenic mTh2 cell subpopulations driving allergic inflammation, those that induce immune responses against helminth infection remain unknown. We found that IL-5-producing CXCR6+ST2+CD44+ mTh2 cells play a crucial role in the IL-33-dependent inhibition of the fecundity of helminth, whereas other ST2- mTh2 cells do not. Although both cell types induced the infiltration of granulocytes, especially eosinophils, into the lungs in response to helminth infection, the ST2+ mTh2 cell-induced eosinophils expressed higher levels of major basic protein (MBP), which is important for reducing the fecundity of Nippostrongylus brasiliensis (Nb), than ST2- mTh2 cell-induced ones. Notably, we also found that ST2+ Treg cells but not ST2- Treg cells suppressed CXCR6+ST2+ mTh2 cell-mediated immune responses. Taken together, these findings show that we identified a mechanism against helminth elicited by a subpopulation of IL-5-producing mTh2 cells through the accumulation of eosinophils strongly expressing MBP in the lungs.}, } @article {pmid30275295, year = {2018}, author = {Ash, M and Boyce, JK}, title = {Racial disparities in pollution exposure and employment at US industrial facilities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10636-10641}, pmid = {30275295}, issn = {1091-6490}, mesh = {*Air Pollution ; *Continental Population Groups ; *Employment ; *Environmental Pollution ; *Health Status Disparities ; Humans ; Manufacturing and Industrial Facilities/*statistics & numerical data ; Minority Groups ; *Residence Characteristics ; Social Class ; United States ; }, abstract = {Proximity to industrial facilities can have positive employment effects as well as negative pollution exposure impacts on surrounding communities. Although racial disparities in exposure to industrial air pollution in the United States are well documented, there has been little empirical investigation of whether these disparities are mirrored by employment benefits. We use facility-level data from the US Environmental Protection Agency (EPA) Toxics Release Inventory (TRI) and the US Equal Employment Opportunity Commission EEO-1 database to assess the extent to which the racial and ethnic distribution of industrial employment corresponds to the distribution of exposure to air toxics emitted by the same facilities. The share of pollution risk accruing to minority groups generally exceeds their share of employment and exceeds their share of higher paying jobs by a wide margin. We find no evidence that facilities that create higher pollution risk for surrounding communities provide more jobs in aggregate.}, } @article {pmid30275294, year = {2018}, author = {Ledón-Rettig, CC and Moczek, AP and Ragsdale, EJ}, title = {Diplogastrellus nematodes are sexually transmitted mutualists that alter the bacterial and fungal communities of their beetle host.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10696-10701}, pmid = {30275294}, issn = {1091-6490}, mesh = {Animals ; Bacteria/*growth & development/metabolism ; Biological Evolution ; Coleoptera/growth & development/*microbiology/*parasitology ; Female ; Fungi/*physiology ; Male ; Nematoda/*physiology ; *Sexually Transmitted Diseases ; *Symbiosis ; }, abstract = {A recent accumulation of studies has demonstrated that nongenetic, maternally transmitted factors are often critical to the health and development of offspring and can therefore play a role in ecological and evolutionary processes. In particular, microorganisms such as bacteria have been championed as heritable, symbiotic partners capable of conferring fitness benefits to their hosts. At the same time, parents may also pass various nonmicrobial organisms to their offspring, yet the roles of such organisms in shaping the developmental environment of their hosts remain largely unexplored. Here, we show that the nematode Diplogastrellus monhysteroides is transgenerationally inherited and sexually transmitted by the dung beetle Onthophagus taurus By manipulating artificial chambers in which beetle offspring develop, we demonstrate that the presence of D. monhysteroides nematodes enhances the growth of beetle offspring, empirically challenging the paradigm that nematodes are merely commensal or even detrimental to their insect hosts. Finally, our research presents a compelling mechanism whereby the nematodes influence the health of beetle larvae: D. monhysteroides nematodes engineer the bacterial and fungal communities that also inhabit the beetle developmental chambers, including specific taxa known to be involved in biomass degradation, possibly allowing larval beetles better access to their otherwise recalcitrant, plant-based diet. Thus, our findings illustrate that nongenetic inheritance can include intermediately sized organisms that live and proliferate in close association with, and in certain cases enhance, the development of their hosts' offspring.}, } @article {pmid30275293, year = {2018}, author = {Raimondo, TM and Mooney, DJ}, title = {Functional muscle recovery with nanoparticle-directed M2 macrophage polarization in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10648-10653}, pmid = {30275293}, issn = {1091-6490}, support = {DP3 DK108224/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Proliferation ; Female ; Gold/*chemistry ; Inflammation/immunology/metabolism/*prevention & control ; Interleukin-4/*administration & dosage/chemistry ; Ischemia/immunology/metabolism/*prevention & control ; Macrophages/*cytology/drug effects/metabolism ; Metal Nanoparticles/*administration & dosage/chemistry ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/cytology/injuries/*physiology ; Phenotype ; Recovery of Function ; }, abstract = {Persistence of inflammation, and associated limits in tissue regeneration, are believed to be due in part to the imbalance of M1 over M2 macrophages. Here, we hypothesized that providing a sustained source of an antiinflammatory polarizing cytokine would shift the balance of macrophages at a site of tissue damage to improve functional regeneration. Specifically, IL-4-conjugated gold nanoparticles (PA4) were injected into injured murine skeletal muscle, resulting in improved histology and an ∼40% increase in muscle force compared with mice treated with vehicle only. Macrophages were the predominant infiltrating immune cell, and treatment with PA4 resulted in an approximately twofold increase in the percentage of macrophages expressing the M2a phenotype and an approximately twofold decrease in M1 macrophages, compared with mice treated with vehicle only. Intramuscular injection of soluble IL-4 did not shift macrophage polarization or result in functional muscle improvements. Depletion of monocytes/macrophages eliminated the therapeutic effects of PA4, suggesting that improvement in muscle function was the result of M2-shifted macrophage polarization. The ability of PA4 to direct macrophage polarization in vivo may be beneficial in the treatment of many injuries and inflammatory diseases.}, } @article {pmid30275292, year = {2018}, author = {}, title = {Correction for Mittal et al., Codon usage influences fitness through RNA toxicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9753}, doi = {10.1073/pnas.1815812115}, pmid = {30275292}, issn = {1091-6490}, } @article {pmid30275277, year = {2018}, author = {Patterson, AP and Groesch, ME and Shipp, AC and Viggiani, CJ}, title = {At the Crossroads of Science and Society: Careers in Science Policy.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a032854}, pmid = {30275277}, issn = {1943-0264}, abstract = {Science policy offers a challenging and rewarding career path for scientists interested in the social, ethical, and legal implications of their field. This topic encompasses a broad spectrum of activities all in support of advancing the scientific enterprise. Science policy spans various sectors, and policy careers are found in many different organizations, including the federal government, scientific societies, and professional organizations. Although their specific duties may vary greatly, science policy professionals generally apply their scientific training to ensure that the scientific enterprise advances in a responsible and ethical manner and to solve challenges with broad scientific and societal implications.}, } @article {pmid30275276, year = {2018}, author = {Herschlag, D and Bonilla, S and Bisaria, N}, title = {The Story of RNA Folding, as Told in Epochs.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a032433}, pmid = {30275276}, issn = {1943-0264}, abstract = {SUMMARYThe past decades have witnessed tremendous developments in our understanding of RNA biology. At the core of these advances have been studies aimed at discerning RNA structure and at understanding the forces that influence the RNA folding process. It is easy to take the present state of understanding for granted, but there is much to be learned by considering the path to our current understanding, which has been tortuous, with the birth and death of models, the adaptation of experimental tools originally developed for characterization of protein structure and catalysis, and the development of novel tools for probing RNA. In this review we tour the stages of RNA folding studies, considering them as "epochs" that can be generalized across scientific disciplines. These epochs span from the discovery of catalytic RNA, through biophysical insights into the putative primordial RNA World, to characterization of structured RNAs, the building and testing of models, and, finally, to the development of models with the potential to yield generalizable predictive and quantitative models for RNA conformational, thermodynamic, and kinetic behavior. We hope that this accounting will aid others as they navigate the many fascinating questions about RNA and its roles in biology, in the past, present, and future.}, } @article {pmid30275275, year = {2018}, author = {Bevilacqua, PC and Assmann, SM}, title = {Technique Development for Probing RNA Structure In Vivo and Genome-Wide.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a032250}, pmid = {30275275}, issn = {1943-0264}, abstract = {SUMMARYHow organisms perceive and respond to their surroundings is one of the great questions in biology. It is clear that RNA plays key roles in sensing. Cellular and environmental cues that RNA responds to include temperature, ions, metabolites, and biopolymers. Recent advances in next-generation sequencing and in vivo chemical probing have provided unprecedented insights into RNA folding in vivo and genome-wide. Patterns of chemical reactivity have implicated control of gene expression by RNA and aided prediction of RNA structure. Central to these advances has been development of molecular biological and chemical techniques. Key advances are improvements in the quality, cost, and throughput of library preparation; availability of a wider array of chemicals for probing RNA structure in vivo; and robustness and user friendliness of data analysis. Insights from probing transcriptomes and future directions are provided.}, } @article {pmid30274697, year = {2019}, author = {Salavati, R and Gazestani, VH}, title = {Gene Function Discovery for Kinetoplastid Pathogens.}, journal = {Trends in parasitology}, volume = {35}, number = {1}, pages = {8-12}, doi = {10.1016/j.pt.2018.09.003}, pmid = {30274697}, issn = {1471-5007}, abstract = {We propose to integrate the existing and new experimental data with computational tools to model interaction networks for the most prominent kinetoplastid pathogens. These interaction networks will vastly expand the functional annotation of the kinetoplastid genomes, which in turn are critical for identifying new routes of disease intervention.}, } @article {pmid30273757, year = {2019}, author = {Thirugnanasambandam, R and Inbakandan, D and Kumar, C and Subashni, B and Vasantharaja, R and Stanley Abraham, L and Ayyadurai, N and Sriyutha Murthy, P and Kirubagaran, R and Ajmal Khan, S and Balasubramanian, T}, title = {Genomic insights of Vibrio harveyi RT-6 strain, from infected "Whiteleg shrimp" (Litopenaeus vannamei) using Illumina platform.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {35-44}, doi = {10.1016/j.ympev.2018.09.015}, pmid = {30273757}, issn = {1095-9513}, abstract = {The pathogenicity of "Vibriosis" in shrimps imposes prominent menace to the sustainable growth of mariculture economy. Often the disease outbreak is associated speciously with Vibrio harveyi and its closely related species. The present study investigated the complete genome of the strain V. harveyi RT-6 to explore the molecular mechanism of pathogenesis. The genome of V. harveyi possesses a single chromosome of 6,374,398 bp in size, G + C content (44.7%) and 5730 protein coding genes. The reads of 1.3 Gb were retained from Illumina Hiseq 2500 sequencing method, assembled into 5912 predicted genes, 114 tRNAs genes, and 11 rRNAs genes. Unigenes were annotated by matching against Clusters of Orthologous Groups of proteins (COG)-5730, Gene ontology (GO)-1088, and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases-3401. Furthermore, 13 insertion sequences-(IS), virulence factors and prophage regions were also identified. A total of 94 pathogenic genes and 36 virulence factor genes were mainly identified using Virulence Factors Database (VFDB). Out of the 36 virulence factors, 23 genes responsible for encoding flagella-based motility protein were exclusively predicted to take part in pathogenic mechanism. The Whole Genome Sequencing (WGS) of the strain RT-6 (accession number: SRR5410471) highlighted the underlying genes and specifically accountable functional genes that were responsible for pathogenic infections in shrimps.}, } @article {pmid30273756, year = {2019}, author = {López-Estrada, EK and Sanmartín, I and García-París, M and Zaldívar-Riverón, A}, title = {High extinction rates and non-adaptive radiation explains patterns of low diversity and extreme morphological disparity in North American blister beetles (Coleoptera, Meloidae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {156-168}, doi = {10.1016/j.ympev.2018.09.014}, pmid = {30273756}, issn = {1095-9513}, abstract = {Untangling the relationship between morphological evolution and lineage diversification is key to explain global patterns of phenotypic disparity across the Tree of Life. Few studies have examined the relationship between high morphological disparity and extinction. In this study, we infer phylogenetic relationships and lineage divergence times within Eupomphini (Meloidae), a tribe of blister beetles endemic to the arid zone of North America, which exhibits a puzzling pattern of very low species richness but wild variation in morphological diversity across extant taxa. Using Bayesian and maximum likelihood inference, we estimate diversification and phenotypic evolutionary rates and infer the time and magnitude of extinction rate shifts and mass extinction events. Our results suggest that Eupomphini underwent an event of ancient radiation coupled with rapid morphological change, possibly linked to the loss of the evolutionary constraint in the elytral shape. A high extinction background associated to the Miocene-Pliocene transition decimated the diversity within each major clade, resulting in the species-poor genera observed today. Our study supports a connection between high extinction rates and patterns of decoupled phenotypic evolution and lineage diversification, and the possibility of a radiation in the absence of ecological release.}, } @article {pmid30272541, year = {2018}, author = {Luo, T and Liu, Y and Chen, C and Luo, Q and Rao, Q and Huang, M and Tu, J and Lin, Q and Weng, B}, title = {Chryseobacterium aurantiacum sp. nov., isolated from a freshwater pond used for Murray cod (Maccullochella peelii peelii) culture.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3397-3403}, doi = {10.1099/ijsem.0.002987}, pmid = {30272541}, issn = {1466-5034}, mesh = {Animals ; Aquaculture ; Bacterial Typing Techniques ; Base Composition ; China ; Chryseobacterium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Perciformes ; *Phylogeny ; Pigmentation ; Ponds/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A yellow-pigmented, Gram-staining-negative, aerobic, non-motile and rod-shaped bacterium, designated strain F30T, was isolated from fresh water of a diseased farmed Murray cod with a profound ulceration pond in Zhejiang province, PR China. Growth was observed at NaCl concentrations of 0.5-3.5 % (w/v) (optimum, 1.5-2.0 %), temperatures of 10-35 °C (optimum, 28 °C) and pH 5.0-9.0 (optimum, 6.5). Phylogenetic analysis based on 16S rRNA gene sequences indicated that F30T represented a member of the genus Chryseobacterium, showing the highest similarity to Chryseobacterium jejuense DSM 19299T (99.0 %) and Chryseobacterium nakagawai NCTC 13529T (99.0 %), and less than 98.7 % similarity to other species of the genus Chryseobacterium with validly published names. The average nucleotide identity and in silico DNA-DNA hybridization values between F30T and the reference strains were 78.4-90.5 % and 2.6-42.5 %, respectively. The results of chemotaxonomic analysis indicated that the fatty acids, as well as the polar lipid profiles of F30T were similar to those of species of the genus Chryseobacterium, and the sole respiratory quinone was MK-6. On the basis of its phylogenetic, chemotaxonomic and phenotypic data, strain F30T represents a novel species, for which the name Chryseobacteriumaurantiacum sp. nov. is proposed. The type strain is F30T (=KCTC 62135T=MCCC 1K03457T).}, } @article {pmid30272540, year = {2018}, author = {Liu, L and Liang, LX and Zhang, XX and Li, LB and Sun, QW}, title = {Mesorhizobium ephedrae sp. nov. isolated from the roots of Ephedra przewalskii in Kumtag desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3615-3620}, doi = {10.1099/ijsem.0.003044}, pmid = {30272540}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; *Desert Climate ; Ephedra/*microbiology ; Fatty Acids/chemistry ; Mesorhizobium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Strain 6GN-30T, a Gram-stain-negative, aerobic, non-spore-forming, rod-shaped, motile bacterium was isolated from Ephedra sinica roots in the Kumtag Desert. On the basis of the 16S rRNA gene sequence, the isolate represented a member of the genus Mesorhizobium of the family Phyllobacteriaceae. The results of a phylogenetic analysis indicated that 6GN-30T was phylogenetically related to Mesorhizobium soliNHI-8T. Strain 6GN-30T grew at a salinity of 0-1.0 % (w/v) NaCl (with optimum growth in the absence of NaCl), pH 6.0-9.0 (optimum 7.0-8.0) and 15-45 °C. The major cellular fatty acids were summed feature 8 (C18 : 1ω7c/C18 : 1ω6c), C19 : 0cyclo ω8c, iso-C17 : 0, C18 : 0, and C16 : 0. The draft genome of 6GN-30T was 6.11 Mb long, with a DNA G+C content of 66.4 mol%. The average nucleotide identity to M. soliNHI-8T was 84.32 %. The strain contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine,aminophospholipids and phospholipids. The chemotaxonomic, phylogenetic and phenotypic data indicate that 6GN-30T represents a novel species of the genus Mesorhizobiumfor which the name Mesorhizobiumephedrae sp. nov. is proposed. The type strain is 6GN-30T (=ACCC 60073T=KCTC 62410T).}, } @article {pmid30272539, year = {2018}, author = {Fogelson, SB and Camus, AC and Lorenz, W and Phillips, A and Bartlett, P and Sanchez, S}, title = {Mycobacterium syngnathidarum sp. nov., a rapidly growing mycobacterium identified in syngnathid fish.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3696-3700}, doi = {10.1099/ijsem.0.002978}, pmid = {30272539}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Genes, Bacterial ; Georgia ; Mycobacterium/*classification/genetics/isolation & purification ; Mycobacterium Infections/microbiology/*veterinary ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Smegmamorpha/*microbiology ; South Carolina ; }, abstract = {Two closely related isolates, 27335T and 24999, of rapidly growing, non-pigmented mycobacteria, were cultured from two clinically ill fish of the family Syngnathidae. Whole genome sequencing of the two isolates revealed low sequence homology to documented mycobacteria within public databases such as the NCBI. Evaluation of targeted housekeeping genes, including 16S rRNA, ITS, rpoB and hsp65, related the two bacteria distantly to Mycobacterium senegalense CK2 M4421 and Mycobacterium farcinogenes DSM 43637. Phenotypic, biochemical and dDNA-DNA hybridization tests demonstrated that Mycobacterium syngnathidarum is a new species distinct from other recognized rapidly growing mycobacterial species. Phenotypic, chemotaxonomic and phylogenetic data evaluation provided evidence that the two strains represent one novel species. We propose the formal recognition of Mycobacterium syngnathidarum sp. nov., with isolate 27335T as the type strain (=ATCC TSD-89T,=DSM 105112T).}, } @article {pmid30272210, year = {2018}, author = {Mathieson, S and Mathieson, I}, title = {FADS1 and the Timing of Human Adaptation to Agriculture.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2957-2970}, pmid = {30272210}, issn = {1537-1719}, abstract = {Variation at the FADS1/FADS2 gene cluster is functionally associated with differences in lipid metabolism and is often hypothesized to reflect adaptation to an agricultural diet. Here, we test the evidence for this relationship using both modern and ancient DNA data. We show that almost all the inhabitants of Europe carried the ancestral allele until the derived allele was introduced ∼8,500 years ago by Early Neolithic farming populations. However, we also show that it was not under strong selection in these populations. We find that this allele, and other proposed agricultural adaptations at LCT/MCM6 and SLC22A4, were not strongly selected until much later, perhaps as late as the Bronze Age. Similarly, increased copy number variation at the salivary amylase gene AMY1 is not linked to the development of agriculture although, in this case, the putative adaptation precedes the agricultural transition. Our analysis shows that selection at the FADS locus was not tightly linked to the initial introduction of agriculture and the Neolithic transition. Further, it suggests that the strongest signals of recent human adaptation in Europe did not coincide with the Neolithic transition but with more recent changes in environment, diet, or efficiency of selection due to increases in effective population size.}, } @article {pmid30271570, year = {2018}, author = {Peters, K and Gorzolka, K and Bruelheide, H and Neumann, S}, title = {Seasonal variation of secondary metabolites in nine different bryophytes.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9105-9117}, pmid = {30271570}, issn = {2045-7758}, abstract = {Bryophytes occur in almost all land ecosystems and contribute to global biogeochemical cycles, ecosystem functioning, and influence vegetation dynamics. As growth and biochemistry of bryophytes are strongly dependent on the season, we analyzed metabolic variation across seasons with regard to ecological characteristics and phylogeny. Using bioinformatics methods, we present an integrative and reproducible approach to connect ecology with biochemistry. Nine different bryophyte species were collected in three composite samples in four seasons. Untargeted liquid chromatography coupled with mass spectrometry (LC/MS) was performed to obtain metabolite profiles. Redundancy analysis, Pearson's correlation, Shannon diversity, and hierarchical clustering were used to determine relationships among species, seasons, ecological characteristics, and hierarchical clustering. Metabolite profiles of Marchantia polymorpha and Fissidens taxifolius which are species with ruderal life strategy (R-selected) showed low seasonal variability, while the profiles of the pleurocarpous mosses and Grimmia pulvinata which have characteristics of a competitive strategy (C-selected) were more variable. Polytrichum strictum and Plagiomnium undulatum had intermediary life strategies. Our study revealed strong species-specific differences in metabolite profiles between the seasons. Life strategies, growth forms, and indicator values for light and soil were among the most important ecological predictors. We demonstrate that untargeted Eco-Metabolomics provide useful biochemical insight that improves our understanding of fundamental ecological strategies.}, } @article {pmid30271569, year = {2018}, author = {Hloušková, M and Balogová, M and Kršáková, V and Gvoždík, L}, title = {No trade-offs in interspecific interference ability and predation susceptibility in newt larvae.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9095-9104}, pmid = {30271569}, issn = {2045-7758}, abstract = {Coexistence of species with similar requirements is allowed, among others, through trade-offs between competitive ability and other ecological traits. Although interspecific competition is based on two mechanisms, exploitation of resources and physical interference, trade-off studies largely consider only species' ability to exploit resources. Using a mesocosm experiment, we examined the trade-off between interference competition ability and susceptibility to predation in larvae of two newt species, Ichthyosaura alpestris and Lissotriton vulgaris. In the presence of heterospecifics, L. vulgaris larvae slowed somatic growth and developmental rates, and experienced a higher frequency of injuries than in conspecific environments which suggests asymmetrical interspecific interference. During short-term predation trials, L. vulgaris larvae suffered higher mortality than I. alpestris. Larvae of the smaller species, L. vulgaris, had both lower interference and antipredator performance than the larger I. alpestris, which suggests a lack of trade-off between interference competition ability and predator susceptibility. We conclude that interference competition may produce a positive rather than negative relationship with predation susceptibility, which may contribute to the elimination of subordinate species from common habitats.}, } @article {pmid30271568, year = {2018}, author = {Kotta, J and Valdivia, N and Kutser, T and Toming, K and Rätsep, M and Orav-Kotta, H}, title = {Predicting the cover and richness of intertidal macroalgae in remote areas: a case study in the Antarctic Peninsula.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9086-9094}, pmid = {30271568}, issn = {2045-7758}, abstract = {Antarctica is an iconic region for scientific explorations as it is remote and a critical component of the global climate system. Recent climate change causes a dramatic retreat of ice in Antarctica with associated impacts to its coastal ecosystem. These anthropogenic impacts have a potential to increase habitat availability for Antarctic intertidal assemblages. Assessing the extent and ecological consequences of these changes requires us to develop accurate biotic baselines and quantitative predictive tools. In this study, we demonstrated that satellite-based remote sensing, when used jointly with in situ ground-truthing and machine learning algorithms, provides a powerful tool to predict the cover and richness of intertidal macroalgae. The salient finding was that the Sentinel-based remote sensing described a significant proportion of variability in the cover and richness of Antarctic macroalgae. The highest performing models were for macroalgal richness and the cover of green algae as opposed to the model of brown and red algal cover. When expanding the geographical range of the ground-truthing, even involving only a few sample points, it becomes possible to potentially map other Antarctic intertidal macroalgal habitats and monitor their dynamics. This is a significant milestone as logistical constraints are an integral part of the Antarctic expeditions. The method has also a potential in other remote coastal areas where extensive in situ mapping is not feasible.}, } @article {pmid30271567, year = {2018}, author = {Odadi, WO and Charles, GK and Young, TP}, title = {Cattle select African savanna termite mound patches less when sharing habitat with wild herbivores.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9074-9085}, pmid = {30271567}, issn = {2045-7758}, abstract = {African savanna termite mounds function as nutrient-rich foraging hotspots for different herbivore species, but little is known about their effects on the interaction between domestic and wild herbivores. Understanding such effects is important for better management of these herbivore guilds in landscapes where they share habitats. Working in a central Kenyan savanna ecosystem, we compared selection of termite mound patches by cattle between areas cattle accessed exclusively and areas they shared with wild herbivores. Termite mound selection index was significantly lower in the shared areas than in areas cattle accessed exclusively. Furthermore, cattle used termite mounds in proportion to their availability when they were the only herbivores present, but used them less than their availability when they shared foraging areas with wild herbivores. These patterns were associated with reduced herbage cover on termite mounds in the shared foraging areas, partly indicating that cattle and wild herbivores compete for termite mound forage. However, reduced selection of termite mound patches was also reinforced by higher leafiness of Brachiaria lachnantha (the principal cattle diet forage species) off termite mounds in shared than in unshared areas. Taken together, these findings suggest that during wet periods, cattle can overcome competition for termite mounds by taking advantage of wildlife-mediated increased forage leafiness in the matrix surrounding termite mounds. However, this advantage is likely to dissipate during dry periods when forage conditions deteriorate across the landscape and the importance of termite mounds as nutrient hotspots increases for both cattle and wild herbivores. Therefore, we suggest that those managing for both livestock production and wildlife conservation in such savanna landscapes should adopt grazing strategies that could lessen competition for forage on termite mounds, such as strategically decreasing stock numbers during dry periods.}, } @article {pmid30271566, year = {2018}, author = {Garlovsky, MD and Snook, RR}, title = {Persistent postmating, prezygotic reproductive isolation between populations.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9062-9073}, pmid = {30271566}, issn = {2045-7758}, abstract = {Studying reproductive barriers between populations of the same species is critical to understand how speciation may proceed. Growing evidence suggests postmating, prezygotic (PMPZ) reproductive barriers play an important role in the evolution of early taxonomic divergence. However, the contribution of PMPZ isolation to speciation is typically studied between species in which barriers that maintain isolation may not be those that contributed to reduced gene flow between populations. Moreover, in internally fertilizing animals, PMPZ isolation is related to male ejaculate-female reproductive tract incompatibilities but few studies have examined how mating history of the sexes can affect the strength of PMPZ isolation and the extent to which PMPZ isolation is repeatable or restricted to particular interacting genotypes. We addressed these outstanding questions using multiple populations of Drosophila montana. We show a recurrent pattern of PMPZ isolation, with flies from one population exhibiting reproductive incompatibility in crosses with all three other populations, while those three populations were fully fertile with each other. Reproductive incompatibility is due to lack of fertilization and is asymmetrical, affecting female fitness more than males. There was no effect of male or female mating history on reproductive incompatibility, indicating that PMPZ isolation persists between populations. We found no evidence of variability in fertilization outcomes attributable to different female × male genotype interactions, and in combination with our other results, suggests that PMPZ isolation is not driven by idiosyncratic genotype × genotype interactions. Our results show PMPZ isolation as a strong, consistent barrier to gene flow early during speciation and suggest several targets of selection known to affect ejaculate-female reproductive tract interactions within species that may cause this PMPZ isolation.}, } @article {pmid30271565, year = {2018}, author = {Wirsing, AJ and Quinn, TP and Cunningham, CJ and Adams, JR and Craig, AD and Waits, LP}, title = {Alaskan brown bears (Ursus arctos) aggregate and display fidelity to foraging neighborhoods while preying on Pacific salmon along small streams.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9048-9061}, pmid = {30271565}, issn = {2045-7758}, abstract = {The interaction between brown bears (Ursus arctos) and Pacific salmon (Oncorhynchus spp.) is important to the population dynamics of both species and a celebrated example of consumer-mediated nutrient transport. Yet, much of the site-specific information we have about the bears in this relationship comes from observations at a few highly visible but unrepresentative locations and a small number of radio-telemetry studies. Consequently, our understanding of brown bear abundance and behavior at more cryptic locations where they commonly feed on salmon, including small spawning streams, remains limited. We employed a noninvasive genetic approach (barbed wire hair snares) over four summers (2012-2015) to document patterns of brown bear abundance and movement among six spawning streams for sockeye salmon, O. nerka, in southwestern Alaska. The streams were grouped into two trios on opposite sides of Lake Aleknagik. Thus, we predicted that most bears would forage within only one trio during the spawning season because of the energetic costs associated with swimming between them or traveling around the lake and show fidelity to particular trios across years because of the benefits of familiarity with local salmon dynamics and stream characteristics. Huggins closed-capture models based on encounter histories from genotyped hair samples revealed that as many as 41 individuals visited single streams during the annual 6-week sampling season. Bears also moved freely among trios of streams but rarely moved between these putative foraging neighborhoods, either during or between years. By implication, even small salmon spawning streams can serve as important resources for brown bears, and consistent use of stream neighborhoods by certain bears may play an important role in spatially structuring coastal bear populations. Our findings also underscore the efficacy of noninvasive hair snagging and genetic analysis for examining bear abundance and movements at relatively fine spatial and temporal scales.}, } @article {pmid30271564, year = {2018}, author = {Hunter, ME and Johnson, NA and Smith, BJ and Davis, MC and Butterfield, JSS and Snow, RW and Hart, KM}, title = {Cytonuclear discordance in the Florida Everglades invasive Burmese python (Python bivittatus) population reveals possible hybridization with the Indian python (P. molurus).}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9034-9047}, pmid = {30271564}, issn = {2045-7758}, abstract = {The invasive Burmese python (Python bivittatus) has been reproducing in the Florida Everglades since the 1980s. These giant constrictor snakes have caused a precipitous decline in small mammal populations in southern Florida following escapes or releases from the commercial pet trade. To better understand the invasion pathway and genetic composition of the population, two mitochondrial (mtDNA) loci across 1,398 base pairs were sequenced on 426 snakes and 22 microsatellites were assessed on 389 snakes. Concatenated mtDNA sequences produced six haplotypes with an average nucleotide and haplotype diversity of π = 0.002 and h = 0.097, respectively. Samples collected in Florida from morphologically identified P. bivittatus snakes were similar to published cytochrome oxidase 1 and cytochrome b sequences from both P. bivittatus and Python molurus and were highly divergent (genetic distances of 5.4% and 4.3%, respectively). The average number of microsatellite alleles and expected heterozygosity were NA = 5.50 and HE = 0.60, respectively. Nuclear Bayesian assignment tests supported two genetically distinct groups and an admixed group, not geographically differentiated. The effective population size (NE = 315.1) was lower than expected for a population this large, but reflected the low genetic diversity overall. The patterns of genetic diversity between mtDNA and microsatellites were disparate, indicating nuclear introgression of separate mtDNA lineages corresponding to cytonuclear discordance. The introgression likely occurred prior to the invasion, but genetic information on the native range and commercial trade is needed for verification. Our finding that the Florida python population is comprised of distinct lineages suggests greater standing variation for adaptation and the potential for broader areas of suitable habitat in the invaded range.}, } @article {pmid30271563, year = {2018}, author = {Ditmer, MA and Fieberg, JR and Moen, RA and Windels, SK and Stapleton, SP and Harris, TR}, title = {Moose movement rates are altered by wolf presence in two ecosystems.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9017-9033}, pmid = {30271563}, issn = {2045-7758}, abstract = {Predators directly impact prey populations through lethal encounters, but understanding nonlethal, indirect effects is also critical because foraging animals often face trade-offs between predator avoidance and energy intake. Quantifying these indirect effects can be difficult even when it is possible to monitor individuals that regularly interact. Our goal was to understand how movement and resource selection of a predator (wolves; Canis lupus) influence the movement behavior of a prey species (moose; Alces alces). We tested whether moose avoided areas with high predicted wolf resource use in two study areas with differing prey compositions, whether avoidance patterns varied seasonally, and whether daily activity budgets of moose and wolves aligned temporally. We deployed GPS collars on both species at two sites in northern Minnesota. We created seasonal resource selection functions (RSF) for wolves and modeled the relationship between moose first-passage time (FPT), a method that discerns alterations in movement rates, and wolf RSF values. Larger FPT values suggest rest/foraging, whereas shorter FPT values indicate travel/fleeing. We found that the movements of moose and wolves peaked at similar times of day in both study areas. Moose FPTs were 45% lower in areas most selected for by wolves relative to those avoided. The relationship between wolf RSF and moose FPT was nonlinear and varied seasonally. Differences in FPT between low and high RSF values were greatest in winter (-82.1%) and spring (-57.6%) in northeastern Minnesota and similar for all seasons in the Voyageurs National Park ecosystem. In northeastern Minnesota, where moose comprise a larger percentage of wolf diet, the relationship between moose FPT and wolf RSF was more pronounced (ave. across seasons: -60.1%) than the Voyageurs National Park ecosystem (-30.4%). These findings highlight the role wolves can play in determining moose behavior, whereby moose spend less time in areas with higher predicted likelihood of wolf resource selection.}, } @article {pmid30271562, year = {2018}, author = {Chen, M and Zhao, XY and Zuo, XA}, title = {Pollinator activity and pollination success of Medicago sativa L. in a natural and a managed population.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {9007-9016}, pmid = {30271562}, issn = {2045-7758}, abstract = {Medicago sativa L. is an important cash crop in the arid region of northwest China. Pollinator activity is an essential aspect of pollination success, but the relationships between pollinator visitation rate and seed set still need further study of M. sativa. We investigated the following characteristics of M. sativa in natural and managed populations: floral traits, pollinator activity, and breeding system. Our results indicated the management could affect the number of flowers produced; however, there was no detectable effect on the seed set per flower. We found the percentage of seeds among pollinated flowers in the managed population was significantly higher than that in the natural population. Moreover, the increase in the proportion of pollinated flowers could significantly increase seed set per flower, and pollinator visitation rate was the important limiting factor for seed set in both populations. Andrena lebedevi Popov was found to be the most frequent pollinator in both populations. Outcrossing was dominant in the breeding system and insect pollination played an important role in outcrossing. Our study suggested that proper management (artificial selection) could promote pollination success of M. sativa.}, } @article {pmid30271561, year = {2018}, author = {Dick, C and Hinh, J and Hayashi, CY and Reznick, DN}, title = {Convergent evolution of coloration in experimental introductions of the guppy (Poecilia reticulata).}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8999-9006}, pmid = {30271561}, issn = {2045-7758}, abstract = {Despite the multitude of examples of evolution in action, relatively fewer studies have taken a replicated approach to understand the repeatability of evolution. Here, we examine the convergent evolution of adaptive coloration in experimental introductions of guppies from a high-predation (HP) environment into four low-predation (LP) environments. LP introductions were replicated across 2 years and in two different forest canopy cover types. We take a complementary approach by examining both phenotypes and genetics. For phenotypes, we categorize the whole color pattern on the tail fin of male guppies and analyze evolution using a correspondence analysis. We find that coloration in the introduction sites diverged from the founding Guanapo HP site. Sites group together based on canopy cover, indicating convergence in response to light environment. However, the axis that explains the most variation indicates a lack of convergence. Therefore, evolution may proceed along similar phenotypic trajectories, but still maintain unique variation within sites. For the genetics underlying the divergent phenotypes, we examine expression levels of color genes. We find no evidence for differential expression, indicating that the genetic basis for the color changes remains undetermined.}, } @article {pmid30271560, year = {2018}, author = {Thalinger, B and Oehm, J and Zeisler, C and Vorhauser, J and Traugott, M}, title = {Sex-specific prey partitioning in breeding piscivorous birds examined via a novel, noninvasive approach.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8985-8998}, pmid = {30271560}, issn = {2045-7758}, abstract = {Piscivorous birds frequently display sex-specific differences in their hunting and feeding behavior, which lead to diverging impacts on prey populations. Cormorants (Phalacrocoracidae), for example, were previously studied to examine dietary differences between the sexes and males were found to consume larger fish in coastal areas during autumn and winter. However, information on prey partitioning during breeding and generally on sex-specific foraging in inland waters is missing. Here, we assess sex-specific prey choice of Great Cormorants (Phalacrocorax carbo) during two subsequent breeding seasons in the Central European Alpine foreland, an area characterized by numerous stagnant and flowing waters in close proximity to each other. We developed a unique, noninvasive approach and applied it to regurgitated pellets: molecular cormorant sexing combined with molecular fish identification and fish-length regression analysis performed on prey hard parts. Altogether, 364 pellets delivered information on both, bird sex, and consumed prey. The sexes differed significantly in their overall prey composition, even though Perca fluviatilis, Rutilus rutilus, and Coregonus spp. represented the main food source for both. Albeit prey composition did not indicate the use of different water bodies by the sexes, male diet was characterized by higher prey diversity within a pellet and the consumption of larger fish. The current findings show that female and male cormorants to some extent target the available prey spectrum at different levels. Finally, the comprehensive and noninvasive approach has great potential for application in studies of other piscivorous bird species.}, } @article {pmid30271559, year = {2018}, author = {Fitzer, SC and Torres Gabarda, S and Daly, L and Hughes, B and Dove, M and O'Connor, W and Potts, J and Scanes, P and Byrne, M}, title = {Coastal acidification impacts on shell mineral structure of bivalve mollusks.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8973-8984}, pmid = {30271559}, issn = {2045-7758}, abstract = {Ocean acidification is occurring globally through increasing CO 2 absorption into the oceans creating particular concern for calcifying species. In addition to ocean acidification, near shore marine habitats are exposed to the deleterious effects of runoff from acid sulfate soils which also decreases environmental pH. This coastal acidification is being exacerbated by climate change-driven sea-level rise and catchment-driven flooding. In response to reduction in habitat pH by ocean and coastal acidification, mollusks are predicted to produce thinner shells of lower structural integrity and reduced mechanical properties threatening mollusk aquaculture. Here, we present the first study to examine oyster biomineralization under acid sulfate soil acidification in a region where growth of commercial bivalve species has declined in recent decades. Examination of the crystallography of the shells of the Sydney rock oyster, Saccostrea glomerata, by electron back scatter diffraction analyses revealed that the signal of environmental acidification is evident in the structure of the biomineral. Saccostrea glomerata, shows phenotypic plasticity, as evident in the disruption of crystallographic control over biomineralization in populations living in coastal acidification sites. Our results indicate that reduced sizes of these oysters for commercial sale may be due to the limited capacity of oysters to biomineralize under acidification conditions. As the impact of this catchment source acidification will continue to be exacerbated by climate change with likely effects on coastal aquaculture in many places across the globe, management strategies will be required to maintain the sustainable culture of these key resources.}, } @article {pmid30271558, year = {2018}, author = {Russell, RE and Abbott, RC and Tripp, DW and Rocke, TE}, title = {Local factors associated with on-host flea distributions on prairie dog colonies.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8951-8972}, pmid = {30271558}, issn = {2045-7758}, abstract = {Outbreaks of plague, a flea-vectored bacterial disease, occur periodically in prairie dog populations in the western United States. In order to understand the conditions that are conducive to plague outbreaks and potentially predict spatial and temporal variations in risk, it is important to understand the factors associated with flea abundance and distribution that may lead to plague outbreaks. We collected and identified 20,041 fleas from 6,542 individual prairie dogs of four different species over a 4-year period along a latitudinal gradient from Texas to Montana. We assessed local climate and other factors associated with flea prevalence and abundance, as well as the incidence of plague outbreaks. Oropsylla hirsuta, a prairie dog specialist flea, and Pulex simulans, a generalist flea species, were the most common fleas found on our pairs. High elevation pairs in Wyoming and Utah had distinct flea communities compared with the rest of the study pairs. The incidence of prairie dogs with Yersinia pestis detections in fleas was low (n = 64 prairie dogs with positive fleas out of 5,024 samples from 4,218 individual prairie dogs). The results of our regression models indicate that many factors are associated with the presence of fleas. In general, flea abundance (number of fleas on hosts) is higher during plague outbreaks, lower when prairie dogs are more abundant, and reaches peak levels when climate and weather variables are at intermediate levels. Changing climate conditions will likely affect aspects of both flea and host communities, including population densities and species composition, which may lead to changes in plague dynamics. Our results support the hypothesis that local conditions, including host, vector, and environmental factors, influence the likelihood of plague outbreaks, and that predicting changes to plague dynamics under climate change scenarios will have to consider both host and vector responses to local factors.}, } @article {pmid30271557, year = {2018}, author = {Benevenuto, RF and Hegland, SJ and Töpper, JP and Rydgren, K and Moe, SR and Rodriguez-Saona, C and Seldal, T}, title = {Multiannual effects of induced plant defenses: Are defended plants good or bad neighbors?.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8940-8950}, pmid = {30271557}, issn = {2045-7758}, abstract = {Defenses induced by herbivore feeding or phytohormones such as methyl jasmonate (MeJA) can affect growth, reproduction, and herbivory, not only on the affected individual but also in its neighboring plants. Here, we report multiannual defense, growth, and reproductive responses of MeJA-treated bilberry (Vaccinium myrtillus) and neighboring ramets. In a boreal forest in western Norway, we treated bilberry ramets with MeJA and water (control) and measured responses over three consecutive years. We observed the treatment effects on variables associated with herbivory, growth, and reproduction in the MeJA-treated and untreated ramet and neighboring ramets distanced from 10 to 500 cm. MeJA-treated ramets had fewer grazed leaves and browsed shoots compared to control, with higher effects in 2014 and 2015, respectively. In 2013, growth of control ramets was greater than MeJA-treated ramets. However, MeJA-treated ramets had more flowers and berries than control ramets 2 years after the treatment. The level of insect and mammalian herbivory was also lower in untreated neighboring ramets distanced 10-150 cm and, consistent with responses of MeJA-treated ramets, the stronger effect was also one and 2 years delayed, respectively. The same neighboring ramets had fewer flowers and berries than untreated ramets, indicating a trade-off between defense and reproduction. Although plant-plant effects were observed across all years, the strength varied by the distance between the MeJA-treated ramets and its untreated neighbors. We document that induced defense in bilberry reduces both insect and mammalian herbivory, as well as growth, over multiple seasons. The defense responses occurred in a delayed manner with strongest effects one and 2 years after the induction. Additionally, our results indicate defense signaling between MeJA-treated ramets and untreated neighbors. In summary, this study shows that induced defenses are important ecological strategies not only for the induced individual plant but also for neighboring plants across multiple years in boreal forests.}, } @article {pmid30271556, year = {2018}, author = {Zhou, Y and Chen, S and Hu, G and Mwachala, G and Yan, X and Wang, Q}, title = {Species richness and phylogenetic diversity of seed plants across vegetation zones of Mount Kenya, East Africa.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8930-8939}, pmid = {30271556}, issn = {2045-7758}, abstract = {Mount Kenya is of ecological importance in tropical east Africa due to the dramatic gradient in vegetation types that can be observed from low to high elevation zones. However, species richness and phylogenetic diversity of this mountain have not been well studied. Here, we surveyed distribution patterns for a total of 1,335 seed plants of this mountain and calculated species richness and phylogenetic diversity across seven vegetation zones. We also measured phylogenetic structure using the net relatedness index (NRI) and the nearest species index (NTI). Our results show that lower montane wet forest has the highest level of species richness, density, and phylogenetic diversity of woody plants, while lower montane dry forest has the highest level of species richness, density, and phylogenetic diversity in herbaceous plants. In total plants, NRI and NTI of four forest zones were smaller than three alpine zones. In woody plants, lower montane wet forest and upper montane forest have overdispersed phylogenetic structures. In herbaceous plants, NRI of Afro-alpine zone and nival zone are smaller than those of bamboo zone, upper montane forest, and heath zone. We suggest that compared to open dry forest, humid forest has fewer herbaceous plants because of the closed canopy of woody plants. Woody plants may have climate-dominated niches, whereas herbaceous plants may have edaphic and microhabitat-dominated niches. We also proposed lower and upper montane forests with high species richness or overdispersed phylogenetic structures as the priority areas in conservation of Mount Kenya and other high mountains in the Eastern Afro-montane biodiversity hotspot regions.}, } @article {pmid30271555, year = {2018}, author = {Langeloh, L and Seppälä, O}, title = {Relative importance of chemical attractiveness to parasites for susceptibility to trematode infection.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8921-8929}, pmid = {30271555}, issn = {2045-7758}, abstract = {While the host immune system is often considered the most important physiological mechanism against parasites, precontact mechanisms determining exposure to parasites may also affect infection dynamics. For instance, chemical cues released by hosts can attract parasite transmission stages. We used the freshwater snail Lymnaea stagnalis and its trematode parasite Echinoparyphium aconiatum to examine the role of host chemical attractiveness, physiological condition, and immune function in determining its susceptibility to infection. We assessed host attractiveness through parasite chemo-orientation behavior; physiological condition through host body size, food consumption, and respiration rate; and immune function through two immune parameters (phenoloxidase-like and antibacterial activity of hemolymph) at an individual level. We found that, although snails showed high variation in chemical attractiveness to E. aconiatum cercariae, this did not determine their overall susceptibility to infection. This was because large body size increased attractiveness, but also increased metabolic activity that reduced overall susceptibility. High metabolic rate indicates fast physiological processes, including immune activity. The examined immune traits, however, showed no association with susceptibility to infection. Our results indicate that postcontact mechanisms were more likely to determine snail susceptibility to infection than variation in attractiveness to parasites. These may include localized immune responses in the target tissue of the parasite. The lack of a relationship between food consumption and attractiveness to parasites contradicts earlier findings that show food deprivation reducing snail attractiveness. This suggests that, although variation in resource level over space and time can alter infection dynamics, variation in chemical attractiveness may not contribute to parasite-induced fitness variation within populations when individuals experience similar environmental conditions.}, } @article {pmid30271554, year = {2018}, author = {Cahill, AE and Pearman, JK and Borja, A and Carugati, L and Carvalho, S and Danovaro, R and Dashfield, S and David, R and Féral, JP and Olenin, S and Šiaulys, A and Somerfield, PJ and Trayanova, A and Uyarra, MC and Chenuil, A}, title = {A comparative analysis of metabarcoding and morphology-based identification of benthic communities across different regional seas.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8908-8920}, pmid = {30271554}, issn = {2045-7758}, abstract = {In a world of declining biodiversity, monitoring is becoming crucial. Molecular methods, such as metabarcoding, have the potential to rapidly expand our knowledge of biodiversity, supporting assessment, management, and conservation. In the marine environment, where hard substrata are more difficult to access than soft bottoms for quantitative ecological studies, Artificial Substrate Units (ASUs) allow for standardized sampling. We deployed ASUs within five regional seas (Baltic Sea, Northeast Atlantic Ocean, Mediterranean Sea, Black Sea, and Red Sea) for 12-26 months to measure the diversity and community composition of macroinvertebrates. We identified invertebrates using a traditional approach based on morphological characters, and by metabarcoding of the mitochondrial cytochrome oxidase I (COI) gene. We compared community composition and diversity metrics obtained using the two methods. Diversity was significantly correlated between data types. Metabarcoding of ASUs allowed for robust comparisons of community composition and diversity, but not all groups were successfully sequenced. All locations were significantly different in taxonomic composition as measured with both kinds of data. We recovered previously known regional biogeographical patterns in both datasets (e.g., low species diversity in the Black and Baltic Seas, affinity between the Bay of Biscay and the Mediterranean). We conclude that the two approaches provide complementary information and that metabarcoding shows great promise for marine monitoring. However, until its pitfalls are addressed, the use of metabarcoding in monitoring of rocky benthic assemblages should be used in addition to classical approaches rather than instead of them.}, } @article {pmid30271553, year = {2018}, author = {Ruehl, CB and Vance-Chalcraft, H and Chalcraft, DR}, title = {Cooccurrence of prey species alters the impact of predators on prey performance through multiple mechanisms.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8894-8907}, pmid = {30271553}, issn = {2045-7758}, abstract = {When prey are differentially affected by intra and interspecific competition, the cooccurrence of multiple prey species alters the per capita availability of food for a particular prey species which could alter how prey respond to the threat of predation, and hence the overall-effect of predators. We conducted an experiment to examine the extent to which the nonconsumptive and overall effect of predatory water bugs on snail and tadpole traits (performance and morphology) depended on whether tadpoles and snails cooccurred. Tadpoles and snails differed in their relative susceptibility to intraspecific and interspecific competition, and predators affected both prey species via consumptive and nonconsumptive mechanisms. Furthermore, the overall effect of predators often depended on whether another prey species was present. The reasoning for why the overall effect of predators depended on whether prey species cooccurred, however, differed for each of the response variables. Predators affected snail body growth via nonconsumptive mechanisms, but the change in the overall effect of predators on snail body growth was attributable to how snails responded to competition in the absence of predators, rather than a change in how snails responded to the threat of predation. Predators did not affect tadpole body growth via nonconsumptive mechanisms, but the greater vulnerability of competitively superior prey (snails) to predators increased the strength of consumptive mechanisms (and hence the overall effect) through which predators affected tadpole growth. Predators affected tadpole morphology via nonconsumptive mechanisms, but the greater propensity for predators to kill competitively superior prey (snails) enhanced the ability of tadpoles to alter their morphology in response to the threat of predation by creating an environment where tadpoles had a higher per capita supply of food available to invest in the development of morphological defenses. Our work indicates that the mechanisms through which predators affect prey depends on the other members of the community.}, } @article {pmid30271552, year = {2018}, author = {Hoffmann, J and Wittchen, U and Berger, G and Stachow, U}, title = {Moving window growth-A method to characterize the dynamic growth of crops in the context of bird abundance dynamics with the example of Skylark (Alauda arvensis).}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8880-8893}, pmid = {30271552}, issn = {2045-7758}, abstract = {Agricultural field crops differ in their vegetation height, coverage, and temporal development, affecting the abundances of bird species, which are often used as bioindicators. Although this relationship has been observed, no significant methodology exists to describe the dynamics of field crop growth on a landscape scale in connection with the abundance of indicator bird species that allows meaningful interpretation of bird abundance data with respect to crop vegetation parameters during the breeding season. In a field observation program, we monitored 2,900 ha of agricultural landscape to represent both the crop growth processes and the bird abundances. We measured these two parameters in the study area, dominated by winter wheat, winter rapeseed, maize, and fallow fields, and adapted the moving window approach to a new method of "moving window growth" to describe the dynamic development of height and coverage of the crops over time. Simultaneously, Skylarks (Alauda arvensis) territorial behavior was measured concurrently on the same fields and crops. Their dynamic abundance was documented over the breeding season. To test the relationship between crop growth and development and bird abundance, we applied a generalized linear model (GLM) in two ways: (a) without differentiation of crop species and (b) with differentiation of crop species. We found significant relationships between bird abundance and vegetation height and coverage with respect to both individual parameters and their interactions, even without differentiation of the agricultural crops. In general, increasing vegetation height and coverage, especially the interaction, led to decreasing bird abundance values. The model quality increased significantly by including differentiation of specific crops as an explanatory variable indicating a non-homogenous situation between crops. Separate models for individual crop species revealed larger differences in model quality with best and least goodness of fit values for fallow fields and winter rapeseed, respectively. Because of the clear interactions between bird abundance, type of field crop, and vegetation height and coverage, it follows that both habitat suitability assessments of arable fields and the definition of favorable vegetation structures for farmland birds should be crop species-specific.}, } @article {pmid30271551, year = {2018}, author = {Fokkema, RW and Ubels, R and Both, C and de Felici, L and Tinbergen, JM}, title = {Reproductive effort and future parental competitive ability: A nest box removal experiment.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8865-8879}, pmid = {30271551}, issn = {2045-7758}, abstract = {The life history trade-off between current and future reproduction is a theoretically well-established concept. However, empirical evidence for the occurrence of a fitness cost of reproduction is mixed. Evidence indicates that parents only pay a cost of reproduction when local competition is high. In line with this, recent experimental work on a small passerine bird, the Great tit (Parus major) showed that reproductive effort negatively affected the competitive ability of parents, estimated through competition for high quality breeding sites in spring. In the current study, we further investigate the negative causal relationship between reproductive effort and future parental competitive ability, with the aim to quantify the consequences for parental fitness, when breeding sites are scarce. To this end, we (a) manipulated the family size of Great tit parents and (b) induced severe competition for nest boxes among the parents just before the following breeding season by means of a large-scale nest box removal experiment. Parents increased their feeding effort in response to our family size manipulation and we successfully induced competition among the parents the following spring. Against our expectation, we found no effect of last season's family size on the ability of parents to secure a scarce nest box for breeding. In previous years, if detected, the survival cost of reproduction was always paid after midwinter. In this year, parents did pay a survival cost of reproduction before midwinter and thus before the onset of the experiment in early spring. Winter food availability during our study year was exceptionally low, and thus, competition in early winter may have been extraordinarily high. We hypothesize that differences in parental competitive ability due to their previous reproductive effort might have played a role, but before the onset of our experiment and resulted in the payment of the survival cost of reproduction.}, } @article {pmid30271550, year = {2018}, author = {Wu, L and Liu, X and Xu, L and Li, L and Fu, P}, title = {Compound-specific 15N analysis of amino acids: A tool to estimate the trophic position of tropical seabirds in the South China Sea.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8853-8864}, pmid = {30271550}, issn = {2045-7758}, abstract = {Compound-specific 15N analysis of amino acids (AAs) is a powerful tool to determine the trophic position (TP) of organisms. However, it has only been used in a few studies of avian ecology because the AA patterns in the consumer-diet nitrogen trophic discrimination factor (TDFGlu-Phe = ∆15 NGlu-∆15 NPhe) were unknown in birds until recently, and tropical seabirds have never been investigated with this methodology. Here, we explore the application of this method to tropical seabirds. In this study, we recovered the fossilized bones of tropical seabirds from ornithogenic sediments on two coral islands in the Xisha Islands, South China Sea, as well as the bones and muscle of their predominant food source, flying fish (Exocoetus volitans). Compound-specific 15N and 13C analyses of AAs in both seabird and fish bone collagen were conducted. The TP of flying fish was calculated based on a widely used single TDFGlu-Phe approach. We then calculated the TP of tropical seabirds in three different ways: (a) according to the composition of their diet; (b) based on the single TDFGlu-Phe approach; and (c) using a multi-TDFGlu-Phe approach. The results of the multi-TDFGlu-Phe approach were much closer to the results based on the composition of the seabird diet than the results of the single TDFGlu-Phe approach, confirming its applicability for tropical seabirds. For seabird bone samples of different ages, TP determined from the multi-TDFGlu-Phe approach was most similar to that of bulk δ15N of bird collagen, with seabirds occupying higher TPs during the Little Ice Age, as previously shown. In addition, the 13C Suess effect was reflected in the AAs δ13C in our samples. This study applied a compound-specific 15N analysis of AAs to determine the TP of tropical seabirds that has potential to extend to all tropical seabirds many of which are widely distributed and play a key role in the evolution of coral island ecosystems.}, } @article {pmid30271549, year = {2018}, author = {Leys, BA and Marlon, JR and Umbanhowar, C and Vannière, B}, title = {Global fire history of grassland biomes.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8831-8852}, pmid = {30271549}, issn = {2045-7758}, abstract = {Grasslands are globally extensive; they exist in many different climates, at high and low elevations, on nutrient-rich and nutrient-poor soils. Grassland distributions today are closely linked to human activities, herbivores, and fire, but many have been converted to urban areas, forests, or agriculture fields. Roughly 80% of fires globally occur in grasslands each year, making fire a critical process in grassland dynamics. Yet, little is known about the long-term history of fire in grasslands. Here, we analyze sedimentary archives to reconstruct grassland fire histories during the Holocene. Given that grassland locations change over time, we compare several charcoal-based fire reconstructions based on alternative classification schemes: (a) sites from modern grassland locations; (b) sites that were likely grasslands during the mid-Holocene; and (c) sites based on author-derived classifications. We also compare fire histories from grassland sites, forested sites, and all sites globally over the past 12,000 years. Forested versus grassland sites show different trends: grassland burning increased from the early to mid-Holocene, reaching a maximum about 8000-6000 years ago, and subsequently declined, reaching a minimum around 4000 years ago. In contrast, biomass burning in forests increased during the Holocene until about 2000 years ago. Continental grassland fire history reconstructions show opposing Holocene trends in North versus South America, whereas grassland burning in Australia was highly variable in the early Holocene and much more stable after the mid-Holocene. The sharp differences in continental as well as forest versus grassland Holocene fire history trajectories have important implications for our understanding of global biomass burning and its emissions, the global carbon cycle, biodiversity, conservation, and land management.}, } @article {pmid30271548, year = {2018}, author = {Luhring, TM and Vavra, JM and Cressler, CE and DeLong, JP}, title = {Predators modify the temperature dependence of life-history trade-offs.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8818-8830}, pmid = {30271548}, issn = {2045-7758}, abstract = {Although life histories are shaped by temperature and predation, their joint influence on the interdependence of life-history traits is poorly understood. Shifts in one life-history trait often necessitate shifts in another-structured in some cases by trade-offs-leading to differing life-history strategies among environments. The offspring size-number trade-off connects three traits whereby a constant reproductive allocation (R) constrains how the number (O) and size (S) of offspring change. Increasing temperature and size-independent predation decrease size at and time to reproduction which can lower R through reduced time for resource accrual or size-constrained fecundity. We investigated how O, S, and R in a clonal population of Daphnia magna change across their first three clutches with temperature and size-independent predation risk. Early in ontogeny, increased temperature moved O and S along a trade-off curve (constant R) toward fewer larger offspring. Later in ontogeny, increased temperature reduced R in the no-predator treatment through disproportionate decreases in O relative to S. In the predation treatment, R likewise decreased at warmer temperatures but to a lesser degree and more readily traded off S for O whereby the third clutch showed a constant allocation strategy of O versus S with decreasing R. Ontogenetic shifts in S and O rotated in a counterclockwise fashion as temperature increased and more drastically under risk of predation. These results show that predation risk can alter the temperature dependence of traits and their interactions through trade-offs.}, } @article {pmid30271547, year = {2018}, author = {Liu, M and Rubenstein, DR and Cheong, SA and Shen, SF}, title = {Multitasking and the evolution of optimal clutch size in fluctuating environments.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8803-8817}, pmid = {30271547}, issn = {2045-7758}, abstract = {Adaptive studies of avian clutch size variation across environmental gradients have resulted in what has become known as the fecundity gradient paradox, the observation that clutch size typically decreases with increasing breeding season length along latitudinal gradients, but increases with increasing breeding season length along elevational gradients. These puzzling findings challenge the common belief that organisms should reduce their clutch size in favor of additional nesting attempts as the length of the breeding season increases, an approach typically described as a bet-hedging strategy. Here, we propose an alternative hypothesis-the multitasking hypothesis-and show that laying smaller clutches represents a multitasking strategy of switching between breeding and recovery from breeding. Both our individual-based and analytical models demonstrate that a small clutch size strategy is favored during shorter breeding seasons because less time and energy are wasted under the severe time constraints associated with breeding multiply within a season. Our model also shows that a within-generation bet-hedging strategy is not favored by natural selection, even under a high risk of predation and in long breeding seasons. Thus, saving time-wasting less time as a result of an inability to complete a breeding cycle at the end of breeding season-is likely to be the primary benefit favoring the evolution of small avian clutch sizes during short breeding seasons. We also synthesize the seasonality hypothesis (pronounced seasonality leads to larger clutch size) and clutch size-dependent predation hypothesis (larger clutch size causes higher predation risks) within our multitasking hypothesis to develop an integrative model to help resolve the paradox of contrasting patterns of clutch size along elevational and latitudinal gradients. Ultimately, our models provide a new perspective for understanding life-history evolution under fluctuating environments.}, } @article {pmid30271546, year = {2018}, author = {Lee, SR and Kim, BY and Kim, YD}, title = {Genetic diagnosis of a rare myrmecochorous species, Plagiorhegma dubium (Berberidaceae): Historical genetic bottlenecks and strong spatial structures among populations.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8791-8802}, pmid = {30271546}, issn = {2045-7758}, abstract = {Distribution of genetic variation over time and space is relevant to demographic histories and tightly linked to ecological disturbances as well as evolutionary potential of an organism. Therefore, understanding the pattern of genetic diversity is a primary step in conservation and management projects for rare and threatened plant species. We used eight microsatellite markers to examine the level of genetic diversity, spatial structure, and demographic history of Plagiorhegma dubium, a rare myrmecochorous herb, populations sampled across northeast Asia and Siberia. We found low within-population genetic variation associated with historical bottlenecks. Although pairwise FST values were not much higher than the ones found in similar life form species, STRUCTURE and PCoA revealed a clear broadscale spatial pattern of genetic structure. Bayesian clustering (best K = 6) and PCoA identified three populations that are distinctive from neighboring populations in the Korean peninsula, which suggests potential units for conservation and management plans in Korea. MIGRATE-N and BAYESASS showed that both contemporary (0.003-0.045) and historical migration rates (2 × e-5-4.6 × e-4) were low. Our findings provide a good example, where genetic considerations should be integrated for conservation and management plans of rare and threatened species.}, } @article {pmid30271545, year = {2018}, author = {Townsend, AK and Wheeler, SS and Freund, D and Sehgal, RNM and Boyce, WM}, title = {Links between blood parasites, blood chemistry, and the survival of nestling American crows.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8779-8790}, pmid = {30271545}, issn = {2045-7758}, abstract = {Many studies have used the avian hemosporidians (Leucocytozoon, Plasmodium, and Hemoproteus) to test hypotheses of host-parasite co-evolution, yet documented health and survival consequences of these blood parasites vary among studies and generalizations about their pathogenicity are debatable. In general, the negative effects of the hemosporidians are likely to be greatest during acute infections of young birds, yet most previous studies in wild passerines have examined chronic effects in adults. Here, we evaluated responses of nestling American crows (Corvus brachyrhynchos) to acute infection (prevalence and burden), as well as its short- and long-term survival consequences. We used panel of nine hematological and biochemical parameters that are regularly used to evaluate the health of domestic animals, including leukocyte profiles, hematocrit, and plasma proteins. We assessed the effects of infection on survival in a mark-recapture framework. Overall, 56% of crows (n = 321 samples) were infected by at least one of the three genera. Infections by all genera were associated with elevated plasma proteins and globulins, which could indicate an adaptive immune response. However, only Plasmodium infections were associated with low hematocrit (anemia) and lower fledging success, possibly mediated by the negative effect of low hematocrit values on body condition. Moreover, early Plasmodium infection (<40 days of age) had long-term survival implications: it was associated with lower apparent survival probability within 3 years after fledging. These results suggest that young crows mounted an adaptive immune response to all three genera. Short- and long-term pathological effects, however, were only apparent with Plasmodium infections.}, } @article {pmid30271544, year = {2018}, author = {Li, Y and Yang, Y and Yu, L and Du, X and Ren, G}, title = {Plastomes of nine hornbeams and phylogenetic implications.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8770-8778}, pmid = {30271544}, issn = {2045-7758}, abstract = {Poor phylogenetic resolution and inconsistency of gene trees are major complications when attempting to construct trees of life for various groups of organisms. In this study, we addressed these issues in analyses of the genus Carpinus (hornbeams) of the Betulaceae. We assembled and annotated the chloroplast (cp) genomes (plastomes) of nine hornbeams representing main clades previously distinguished in this genus. All nine plastomes are highly conserved, with four regions, and about 158-160 kb long, including 121-123 genes. Phylogenetic analyses of whole plastome sequences, noncoding sequences, and the well-aligned coding genes resulted in high resolution of the sampled species in contrast to the failure based on a few cpDNA markers. Phylogenetic relationships in a few clades based only on the coding genes are slightly inconsistent with those based on the noncoding and total plastome datasets. Moreover, these plastome trees are highly incongruent with those based on bi-parentally inherited internal transcribed spacer (ITS) sequence variations. Such high inconsistencies suggest widespread occurrence of incomplete lineage sorting and hybrid introgression during diversification of these hornbeams.}, } @article {pmid30271543, year = {2018}, author = {Kehoe, RC and Cruse, D and Sanders, D and Gaston, KJ and van Veen, FJF}, title = {Shifting daylength regimes associated with range shifts alter aphid-parasitoid community dynamics.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8761-8769}, pmid = {30271543}, issn = {2045-7758}, abstract = {With climate change leading to poleward range expansion of species, populations are exposed to new daylength regimes along latitudinal gradients. Daylength is a major factor affecting insect life cycles and activity patterns, so a range shift leading to new daylength regimes is likely to affect population dynamics and species interactions; however, the impact of daylength in isolation on ecological communities has not been studied so far. Here, we tested for the direct and indirect effects of two different daylengths on the dynamics of experimental multitrophic insect communities. We compared the community dynamics under "southern" summer conditions of 14.5-hr daylight to "northern" summer conditions of 22-hr daylight. We show that food web dynamics indeed respond to daylength with one aphid species (Acyrthosiphon pisum) reaching much lower population sizes at the northern daylength regime compared to under southern conditions. In contrast, in the same communities, another aphid species (Megoura viciae) reached higher population densities under northern conditions. This effect at the aphid level was driven by an indirect effect of daylength causing a change in competitive interaction strengths, with the different aphid species being more competitive at different daylength regimes. Additionally, increasing daylength also increased growth rates in M. viciae making it more competitive under summer long days. As such, the shift in daylength affected aphid population sizes by both direct and indirect effects, propagating through species interactions. However, contrary to expectations, parasitoids were not affected by daylength. Our results demonstrate that range expansion of whole communities due to climate change can indeed change interaction strengths between species within ecological communities with consequences for community dynamics. This study provides the first evidence of daylength affecting community dynamics, which could not be predicted from studying single species separately.}, } @article {pmid30271542, year = {2018}, author = {Jaworski, KE and Lattanzio, MS and Hickerson, CM and Anthony, CD}, title = {Male mate preference as an agent of fecundity selection in a polymorphic salamander.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8750-8760}, pmid = {30271542}, issn = {2045-7758}, abstract = {Color polymorphisms are associated with variation in other traits which may affect individual fitness, and these color-trait associations are expected to contribute to nonrandom mating in polymorphic species. The red-backed salamander (Plethodon cinereus) exhibits a polymorphism in dorsal pattern: striped and unstriped, and previous studies have suggested that they may mate nonrandomly. However, the mechanism(s) contributing to this behavior remain unclear. Here we consider the role that male preference may have in driving mating behavior in P. cinereus. We limit our focus to striped individuals because this morph is most likely to be choosy given their dominant, aggressive behavioral profiles relative to unstriped males. Specifically, we evaluated (a) whether striped males preferentially associate with females with respect to her dorsum color, size, and body condition and (b) if so, whether female traits are evaluated via visual or chemical cues. We also considered whether the frequency of another male social behavior, nose taps, was associated with mate preferences. We found that striped male P. cinereus nose tapped more often to preferred females. However, males only assessed potential mates via chemical cues, preferring larger females overall. Reproductive phenology data on a sample of gravid females drawn from the same population indicated that the color morphs do not differ in reproductive traits, but larger females have greater fecundity. Given our findings, we conclude that female P. cinereus are under fecundity selection, mediated by male preference. In this manner, male mating behavior contributes to observations of nonrandom mate associations in this population of P. cinereus.}, } @article {pmid30271541, year = {2018}, author = {Dussex, N and Taylor, HR and Stovall, WR and Rutherford, K and Dodds, KG and Clarke, SM and Gemmell, NJ}, title = {Reduced representation sequencing detects only subtle regional structure in a heavily exploited and rapidly recolonizing marine mammal species.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8736-8749}, pmid = {30271541}, issn = {2045-7758}, abstract = {Next-generation reduced representation sequencing (RRS) approaches show great potential for resolving the structure of wild populations. However, the population structure of species that have shown rapid demographic recovery following severe population bottlenecks may still prove difficult to resolve due to high gene flow between subpopulations. Here, we tested the effectiveness of the RRS method Genotyping-By-Sequencing (GBS) for describing the population structure of the New Zealand fur seal (NZFS, Arctocephalus forsteri), a species that was heavily exploited by the 19th century commercial sealing industry and has since rapidly recolonized most of its former range from a few isolated colonies. Using 26,026 neutral single nucleotide polymorphisms (SNPs), we assessed genetic variation within and between NZFS colonies. We identified low levels of population differentiation across the species range (<1% of variation explained by regional differences) suggesting a state of near panmixia. Nonetheless, we observed subtle population substructure between West Coast and Southern East Coast colonies and a weak, but significant (p = 0.01), isolation-by-distance pattern among the eight colonies studied. Furthermore, our demographic reconstructions supported severe bottlenecks with potential 10-fold and 250-fold declines in response to Polynesian and European hunting, respectively. Finally, we were able to assign individuals treated as unknowns to their regions of origin with high confidence (96%) using our SNP data. Our results indicate that while it may be difficult to detect population structure in species that have experienced rapid recovery, next-generation markers and methods are powerful tools for resolving fine-scale structure and informing conservation and management efforts.}, } @article {pmid30271540, year = {2018}, author = {Cross, PC and van Manen, FT and Viana, M and Almberg, ES and Bachen, D and Brandell, EE and Haroldson, MA and Hudson, PJ and Stahler, DR and Smith, DW}, title = {Estimating distemper virus dynamics among wolves and grizzly bears using serology and Bayesian state-space models.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8726-8735}, pmid = {30271540}, issn = {2045-7758}, abstract = {Many parasites infect multiple hosts, but estimating the transmission across host species remains a key challenge in disease ecology. We investigated the within and across host species dynamics of canine distemper virus (CDV) in grizzly bears (Ursus arctos) and wolves (Canis lupus) of the Greater Yellowstone Ecosystem (GYE). We hypothesized that grizzly bears may be more likely to be exposed to CDV during outbreaks in the wolf population because grizzly bears often displace wolves while scavenging carcasses. We used serological data collected from 1984 to 2014 in conjunction with Bayesian state-space models to infer the temporal dynamics of CDV. These models accounted for the unknown timing of pathogen exposure, and we assessed how different testing thresholds and the potential for testing errors affected our conclusions. We identified three main CDV outbreaks (1999, 2005, and 2008) in wolves, which were more obvious when we used higher diagnostic thresholds to qualify as seropositive. There was some evidence for increased exposure rates in grizzly bears in 2005, but the magnitude of the wolf effect on bear exposures was poorly estimated and depended upon our prior distributions. Grizzly bears were exposed to CDV prior to wolf reintroduction and during time periods outside of known wolf outbreaks, thus wolves are only one of several potential routes for grizzly bear exposures. Our modeling approach accounts for several of the shortcomings of serological data and is applicable to many wildlife disease systems, but is most informative when testing intervals are short. CDV circulates in a wide range of carnivore species, but it remains unclear whether the disease persists locally within the GYE carnivore community or is periodically reintroduced from distant regions with larger host populations.}, } @article {pmid30271539, year = {2018}, author = {Frantz, A and Perga, ME and Guillard, J}, title = {Parasitic versus nutritional regulation of natural fish populations.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8713-8725}, pmid = {30271539}, issn = {2045-7758}, abstract = {Although parasites are expected to affect their host's fitness, quantitative proof for impacts of parasitism on wild populations is hampered by confounding environmental factors, including dietary resource. Herein, we evaluate whether the physiological conditions of European perch (Perca fluviatilis) in three large peri-alpine lakes (Geneva, Annecy, and Bourget) depend on (a) the nutritional status of the juvenile fish, as revealed by stable isotope and fatty acid compositions, (b) the prevalence of the tapeworm Triaenophorus nodulosus, a parasite transmitted to perch through copepod preys, or (c) interactive effects of both factors. At the scale of lake populations, the deficit in growth and fat storage of juvenile perch during their first summer coincides with a high parasite prevalence and also a low quality of dietary resource. Yet, at the individual level, parasites had no evident effect on the growth of the juvenile perch, while impacts on fat storage appeared only at the highest prevalence of the most infected lake. Fatty acid and stable isotope analyses of fish tissue do not reveal any impact of T. nodulosus on diet, physiology, and feeding behaviour of fish within lakes. Overall, we found a low impact of parasitism on the physiological condition and trophic status of juvenile perch at the end of their first summer. We find instead that juvenile perch growth and fat storage, both factors tied to their winter survival, are under strong nutritional constraints. However, the coinciding nutritional constraints and parasite prevalence of perch juveniles in these three lakes may result from the indirect effect of lake nutrient concentrations, which, as a major control of zooplankton communities, simultaneously regulate both the dietary quality of fish prey and the host-parasite encounter rates.}, } @article {pmid30271538, year = {2018}, author = {Bylemans, J and Gleeson, DM and Hardy, CM and Furlan, E}, title = {Toward an ecoregion scale evaluation of eDNA metabarcoding primers: A case study for the freshwater fish biodiversity of the Murray-Darling Basin (Australia).}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8697-8712}, pmid = {30271538}, issn = {2045-7758}, abstract = {High-throughput sequencing of environmental DNA (i.e., eDNA metabarcoding) has become an increasingly popular method for monitoring aquatic biodiversity. At present, such analyses require target-specific primers to amplify DNA barcodes from co-occurring species, and this initial amplification can introduce biases. Understanding the performance of different primers is thus recommended prior to undertaking any metabarcoding initiative. While multiple software programs are available to evaluate metabarcoding primers, all programs have their own strengths and weaknesses. Therefore, a robust in silico workflow for the evaluation of metabarcoding primers will benefit from the use of multiple programs. Furthermore, geographic differences in species biodiversity are likely to influence the performance of metabarcoding primers and further complicate the evaluation process. Here, an in silico workflow is presented that can be used to evaluate the performance of metabarcoding primers on an ecoregion scale. This workflow was used to evaluate the performance of published and newly developed eDNA metabarcoding primers for the freshwater fish biodiversity of the Murray-Darling Basin (Australia). To validate the in silico workflow, a subset of the primers, including one newly designed primer pair, were used in metabarcoding analyses of an artificial DNA community and eDNA samples. The results show that the in silico workflow allows for a robust evaluation of metabarcoding primers and can reveal important trade-offs that need to be considered when selecting the most suitable primer. Additionally, a new primer pair was described and validated that allows for more robust taxonomic assignments and is less influenced by primer biases compared to commonly used fish metabarcoding primers.}, } @article {pmid30271537, year = {2018}, author = {Raine, EH and Gray, CL and Mann, DJ and Slade, EM}, title = {Tropical dung beetle morphological traits predict functional traits and show intraspecific differences across land uses.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8686-8696}, pmid = {30271537}, issn = {2045-7758}, abstract = {Functional traits and functional diversity measures are increasingly being used to examine land use effects on biodiversity and community assembly rules. Morphological traits are often used directly as functional traits. However, behavioral characteristics are more difficult to measure. Establishing methods to derive behavioral traits from morphological measurements is necessary to facilitate their inclusion in functional diversity analyses. We collected morphometric data from over 1,700 individuals of 12 species of dung beetle to establish whether morphological measurements can be used as predictors of behavioral traits. We also compared morphology among individuals collected from different land uses (primary forest, logged forest, and oil palm plantation) to identify whether intraspecific differences in morphology vary among land use types. We show that leg and eye measurements can be used to predict dung beetle nesting behavior and period of activity and we used this information to confirm the previously unresolved nesting behavior for Synapsis ritsemae. We found intraspecific differences in morphological traits across different land use types. Phenotypic plasticity was found for traits associated with dispersal (wing aspect ratio and wing loading) and reproductive capacity (abdomen size). The ability to predict behavioral functional traits from morphology is useful where the behavior of individuals cannot be directly observed, especially in tropical environments where the ecology of many species is poorly understood. In addition, we provide evidence that land use change can cause phenotypic plasticity in tropical dung beetle species. Our results reinforce recent calls for intraspecific variation in traits to receive more attention within community ecology.}, } @article {pmid30271536, year = {2018}, author = {Bernardi, G and Nelson, P and Paddack, M and Rulmal, J and Crane, N}, title = {Genomic islands of divergence in the Yellow Tang and the Brushtail Tang Surgeonfishes.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8676-8685}, pmid = {30271536}, issn = {2045-7758}, abstract = {The current ease of obtaining thousands of molecular markers challenges the notion that full phylogenetic concordance, as proposed by phylogenetic species concepts, is a requirement for defining species delimitations. Indeed, the presence of genomic islands of divergence, which may be the cause, or in some cases the consequence, of speciation, precludes concordance. Here, we explore this issue using thousands of RAD markers on two sister species of surgeonfishes (Teleostei: Acanthuridae), Zebrasoma flavescens and Z. scopas, and several populations within each species. Species are readily distinguished based on their colors (solid yellow and solid brown, respectively), yet populations and species are neither distinguishable using mitochondrial markers (cytochrome c oxidase 1), nor using 5193 SNPs (pairwise Φst = 0.034). In contrast, when using outlier loci, some of them presumably under selection, species delimitations, and strong population structure follow recognized taxonomic positions (pairwise Φst = 0.326). Species and population delimitation differences based on neutral and selected markers are likely due to local adaptation, thus being consistent with the idea that these genomic islands of divergence arose as a consequence of isolation. These findings, which are not unique, raise the question of a potentially important pathway of divergence based on local adaptation that is only evident when looking at thousands of loci.}, } @article {pmid30271535, year = {2018}, author = {Donnelly, K and Cavers, S and Cottrell, JE and Ennos, RA}, title = {Cryptic genetic variation and adaptation to waterlogging in Caledonian Scots pine, Pinus sylvestris L.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8665-8675}, pmid = {30271535}, issn = {2045-7758}, abstract = {Local adaptation occurs as the result of differential selection among populations. Observations made under common environmental conditions may reveal phenotypic differences between populations with an underlying genetic basis; however, exposure to a contrasting novel environment can trigger release of otherwise unobservable (cryptic) genetic variation. We conducted a waterlogging experiment on a common garden trial of Scots pine, Pinus sylvestris (L.), saplings originating from across a steep rainfall gradient in Scotland. A flood treatment was maintained for approximately 1 year; physiological responses were gauged periodically in terms of photochemical capacity as measured via chlorophyll fluorescence. During the treatment, flooded individuals experienced a reduction in photochemical capacity, Fv/Fm, this reduction being greater for material originating from drier, eastern sites. Phenotypic variance was increased under flooding, and this increase was notably smaller in saplings originating from western sites where precipitation is substantially greater and waterlogging is more common. We conclude that local adaptation has occurred with respect to waterlogging tolerance and that, under the flooding treatment, the greater increase in variability observed in populations originating from drier sites is likely to reflect a relative absence of past selection. In view of a changing climate, we note that comparatively maladapted populations may possess considerable adaptive potential, due to cryptic genetic variation, that should not be overlooked.}, } @article {pmid30271534, year = {2018}, author = {Birnbaum, C and Morald, TK and Tibbett, M and Bennett, RG and Standish, RJ}, title = {Effect of plant root symbionts on performance of native woody species in competition with an invasive grass in multispecies microcosms.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8652-8664}, pmid = {30271534}, issn = {2045-7758}, abstract = {The majority of terrestrial plants form mutualistic associations with arbuscular mycorrhizal fungi (AMF) and rhizobia (i.e., nitrogen-fixing bacteria). Understanding these associations has important implications for ecological theory and for restoration practice. Here, we tested whether the presence of AMF and rhizobia influences the performance of native woody plants invaded by a non-native grass in experimental microcosms. We planted eight plant species (i.e., Acacia acuminata, A. microbotrya, Eucalyptus loxophleba subsp. loxophleba, E. astringens, Calothamnus quadrifidus, Callistemon phoeniceus, Hakea lissocarpha and H. prostrata) in microcosms of field-conditioned soil with and without addition of AMF and rhizobia in a fully factorial experimental design. After seedling establishment, we seeded half the microcosms with an invasive grass Bromus diandrus. We measured shoot and root biomass of native plants and Bromus, and on roots, the percentage colonization by AMF, number of rhizobia-forming nodules and number of proteaceous root clusters. We found no effect of plant root symbionts or Bromus addition on performance of myrtaceous, and as predicted, proteaceous species as they rely little or not at all on AMF and rhizobia. Soil treatments with AMF and rhizobia had a strong positive effect (i.e., larger biomass) on native legumes (A. microbotrya and A. acuminata). However, the beneficial effect of root symbionts on legumes became negative (i.e., lower biomass and less nodules) if Bromus was present, especially for one legume, i.e., A. acuminata, suggesting a disruptive effect of the invader on the mutualism. We also found a stimulating effect of Bromus on root nodule production in A. microbotrya and AMF colonization in A. acuminata which could be indicative of legumes' increased resource acquisition requirement, i.e., for nitrogen and phosphorus, respectively, in response to the Bromus addition. We have demonstrated the importance of measuring belowground effects because the aboveground effects gave limited indication of the effects occurring belowground.}, } @article {pmid30271533, year = {2018}, author = {Yu, L and Nie, Y and Yan, L and Hu, Y and Wei, F}, title = {No evidence for MHC-based mate choice in wild giant pandas.}, journal = {Ecology and evolution}, volume = {8}, number = {17}, pages = {8642-8651}, pmid = {30271533}, issn = {2045-7758}, abstract = {Major histocompatibility complex genes (MHC), a gene cluster that controls the immune response to parasites, are regarded as an important determinant of mate choice. However, MHC-based mate choice studies are especially rare for endangered animals. The giant panda (Ailuropoda melanoleuca), a flagship species, has suffered habitat loss and fragmentation. We investigated the genetic variation of three MHC class II loci, including DRB1, DQA1, and DQA2, for 19 mating-pairs and 11 parent-pairs of wild giant pandas based on long-term field behavior observations and genetic samples. We tested four hypotheses of mate choice based on this MHC variation. We found no supporting evidence for the MHC-based heterosis, genetic diversity, genetic compatibility and "good gene" hypotheses. These results suggest that giant pandas may not use MHC-based signals to select mating partners, probably because limited mating opportunities or female-biased natal dispersal restricts selection for MHC-based mate choice, acknowledging the caveat of the small sample size often encountered in endangered animal studies. Our study provides insight into the mate choice mechanisms of wild giant pandas and highlights the need to increase the connectivity and facilitate dispersal among fragmented populations and habitats.}, } @article {pmid30270461, year = {2018}, author = {Law, CJ and Duran, E and Hung, N and Richards, E and Santillan, I and Mehta, RS}, title = {Effects of diet on cranial morphology and biting ability in musteloid mammals.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1918-1931}, doi = {10.1111/jeb.13385}, pmid = {30270461}, issn = {1420-9101}, support = {//National Science Foundation (NSF) Graduate Research Fellowship/ ; //NSF Doctoral Dissertation Improvement Grant/ ; //American Museum of Natural History/ ; //Field Museum/ ; //American Society of Mammalogists/ ; //Society for the Study of Evolution/ ; //Society of Integrative & Comparative Biology/ ; }, abstract = {Size and shape are often considered important variables that lead to variation in performance. In studies of feeding, size-corrected metrics of the skull are often used as proxies of biting performance; however, few studies have examined the relationship between cranial shape in its entirety and estimated bite force across species and how dietary ecologies may affect these variables differently. Here, we used geometric morphometric and phylogenetic comparative approaches to examine relationships between cranial morphology and estimated bite force in the carnivoran clade Musteloidea. We found a strong relationship between cranial size and estimated bite force but did not find a significant relationship between cranial shape and size-corrected estimated bite force. Many-to-one mapping of form to function may explain this pattern because a variety of evolutionary shape changes rather than a single shape change may have contributed to an increase in relative biting ability. We also found that dietary ecologies influenced cranial shape evolution but did not influence cranial size nor size-corrected bite force evolution. Although musteloids with different diets exhibit variation in cranial shapes, they have similar estimated bite forces suggesting that other feeding performance metrics and potentially nonfeeding traits are also important contributors to cranial evolution. We postulate that axial and appendicular adaptations and the interesting feeding behaviours reported for species within this group also facilitate different dietary ecologies between species. Future work integrating cranial, axial and appendicular form and function with behavioural observations will reveal further insights into the evolution of dietary ecologies and other ecological variables.}, } @article {pmid30270425, year = {2018}, author = {Joshi, J and Guttal, V}, title = {Demographic noise and cost of greenbeard can facilitate greenbeard cooperation.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2595-2607}, doi = {10.1111/evo.13615}, pmid = {30270425}, issn = {1558-5646}, support = {DBT-IISc partnership program//Department of Biotechnology , Ministry of Science and Technology/ ; DST-FIST//Department of Science and Technology, Ministry of Science and Technology/ ; Mathematical Biology Phase II (SR/S4/MS:799/12)//Department of Science and Technology, Ministry of Science and Technology/ ; ICTS/Prog-PGE2018/03//International Centre for Theoretical Sciences/ ; }, abstract = {Cooperation among organisms, where cooperators suffer a personal cost to benefit others, is ubiquitous in nature. Greenbeard is a key mechanism for the evolution of cooperation, where a single gene or a set of linked genes codes for both cooperation and a phenotypic tag (metaphorically called "green beard"). Greenbeard cooperation is typically thought to decline over time since defectors can also evolve the tag. However, models of tag-based cooperation typically ignore two key realistic features: populations are finite, and that phenotypic tags can be costly. We develop an analytical model for coevolutionary dynamics of two evolvable traits in finite populations with mutations: costly cooperation and a costly tag. We show that an interplay of demographic noise and cost of the tag can induce coevolutionary cycling, where the evolving population does not reach a steady state but spontaneously switches between cooperative tag-carrying and noncooperative tagless states. Such dynamics allows the tag to repeatedly reappear even after it is invaded by defectors. Thus, we highlight the surprising possibility that the cost of the tag, together with demographic noise, can facilitate the evolution of greenbeard cooperation. We discuss implications of these findings in the context of the evolution of quorum sensing and multicellularity.}, } @article {pmid30270172, year = {2018}, author = {Seppelt, R and Beckmann, M and Václavík, T and Volk, M}, title = {The Art of Scientific Performance.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {805-809}, doi = {10.1016/j.tree.2018.08.003}, pmid = {30270172}, issn = {1872-8383}, abstract = {Humanity builds upon scientific findings, but the credibility of science might be at risk in a 'postfactual' era of advanced information technologies. Here we propose a systemic change for science, to turn away from a growth paradigm and to refocus on quality, characterized by curiosity, surprise, discovery, and societal relevance.}, } @article {pmid30270122, year = {2019}, author = {Fraser, HB}, title = {Improving Estimates of Compensatory cis-trans Regulatory Divergence.}, journal = {Trends in genetics : TIG}, volume = {35}, number = {1}, pages = {3-5}, doi = {10.1016/j.tig.2018.09.003}, pmid = {30270122}, issn = {0168-9525}, abstract = {Interspecific hybrids have played a key role in research on gene expression regulation. A growing number of studies have measured genome-wide allele-specific expression in hybrids and observed that cis-regulatory changes often oppose trans-acting changes affecting the same genes, suggesting stabilizing selection for compensatory changes. However, the most common method for estimating these effects is biased, producing artifactual patterns of compensatory evolution. Here I introduce a simple modification leveraging biological replicates that ameliorates the bias.}, } @article {pmid30269289, year = {2018}, author = {Sibilska, I and Feng, Y and Li, L and Yin, J}, title = {Trimetaphosphate Activates Prebiotic Peptide Synthesis across a Wide Range of Temperature and pH.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {3}, pages = {277-287}, pmid = {30269289}, issn = {1573-0875}, support = {R01AI091646//National Institute of Allergy and Infectious Diseases/ ; U19AI0104317//National Institute of Allergy and Infectious Diseases/ ; R01DK071801//National Institute of Diabetes and Digestive and Kidney Diseases/ ; S10RR029531//National Center for Research Resources/ ; Robert Draper Technology Innovation Fund//Wisconsin Alumni Research Foundation (US)/ ; shared instrument grant//Wisconsin Alumni Research Foundation (US)/ ; Accelerator Fund grant//Wisconsin Alumni Research Foundation (US)/ ; Vilas Distinguished Achievement Professorship//University of Wisconsin-Madison (US)/ ; Vilas Distinguished Achievement Professorship//University of Wisconsin Madison/ ; Janis Apinis Professorship//School of Medicine and Public Health, University of Wisconsin-Madison/ ; }, mesh = {Adenosine Triphosphate/genetics/metabolism ; *Origin of Life ; Peptide Biosynthesis/*genetics ; Polyphosphates/metabolism ; *Prebiotics ; }, abstract = {The biochemical activation of amino acids by adenosine triphosphate (ATP) drives the synthesis of proteins that are essential for all life. On the early Earth, before the emergence of cellular life, the chemical condensation of amino acids to form prebiotic peptides or proteins may have been activated by inorganic polyphosphates, such as tri metaphosphate (TP). Plausible volcanic and other potential sources of TP are known, and TP readily activates amino acids for peptide synthesis. But de novo peptide synthesis also depends on pH, temperature, and processes of solvent drying, which together define a varied range of potential activating conditions. Although we cannot replay the tape of life on Earth, we can examine how activator, temperature, acidity and other conditions may have collectively shaped its prebiotic evolution. Here, reactions of two simple amino acids, glycine and alanine, were tested, with or without TP, over a wide range of temperature (0-100 °C) and acidity (pH 1-12), while open to the atmosphere. After 24 h, products were analyzed by HPLC and mass spectrometry. In the absence of TP, glycine and alanine readily formed peptides under harsh near-boiling temperatures, extremes of pH, and within dry solid residues. In the presence of TP, however, peptides arose over a much wider range of conditions, including ambient temperature, neutral pH, and in water. These results show how polyphosphates such as TP may have enabled the transition of peptide synthesis from harsh to mild early Earth environments, setting the stage for the emergence of more complex prebiotic chemistries.}, } @article {pmid30269253, year = {2018}, author = {Guo, R and Chen, D and Chen, H and Xiong, C and Zheng, Y and Hou, C and Du, Y and Geng, S and Wang, H and Dingding, Z and Yilong, G}, title = {Genome-Wide Identification of Circular RNAs in Fungal Parasite Nosema ceranae.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1655-1660}, pmid = {30269253}, issn = {1432-0991}, support = {CARS-44-KXJ7//Earmarked Fund for Modern Agro-industry Technology Research System/ ; 2018J05042//Science and Technology Planning Project of Fujian Province/ ; JAT170158//Education and Scientific Research Fund of Young Teachers of Fujian Educational Bureau/ ; CXZX2017342//Science and Technology Innovation Fund of Fujian Agriculture and Forestry University/ ; CXZX2017343//Science and Technology Innovation Fund of Fujian Agriculture and Forestry University/ ; 2017MFNZS02//Open Fund of Key Laboratory of Pollinating Insect Biology of Ministry of Agriculture and Rural Affairs/ ; }, mesh = {Animals ; DNA, Fungal/*genetics ; Gene Regulatory Networks/genetics ; High-Throughput Nucleotide Sequencing/methods ; MicroRNAs/genetics ; Nosema/*genetics ; Parasites/*genetics ; RNA/*genetics ; }, abstract = {Circular RNAs (circRNAs) are newly discovered endogenous non-coding RNAs (ncRNAs) that play key roles in microRNA function and transcriptional regulation. Though a large number of circRNAs had been identified in animals and plants, however, little is known regarding circRNAs in Nosema ceranae, a widespread fungal parasite of honeybee. In this study, using deep sequencing technology and bioinformatic analysis, we predicted 204 circRNAs from N. ceranae spore samples, including 174 exonic circRNAs and 30 intergenic circRNAs. In addition, the expression of seven N. ceranae circRNAs was confirmed by RT-PCR assay. Furthermore, regulation networks of circRNAs were constructed, and 15 circRNAs were found to act as sponges of the corresponding three miRNAs. GO categorization and pathway enrichment analysis suggested that the circRNAs are likely to play significant roles in N. ceranae spore. This is the first report of circRNAs generated by a microsporidia species. Our results provide novel insights into understanding the basic biology of N. ceranae.}, } @article {pmid30268714, year = {2018}, author = {Cole, ES and Dmytrenko, O and Chmelik, CJ and Li, M and Christensen, TA and Macon, EP and Nilsson, HJ and Blower, RJ and Reuter, TG and Beckman, JP and Remmers, BC and Smith, CL and O'Toole, E and Ozzello, C and Morgan, G and Giddings, T}, title = {Restoration of cellular integrity following "ballistic" pronuclear exchange during Tetrahymena conjugation.}, journal = {Developmental biology}, volume = {444}, number = {1}, pages = {33-40}, doi = {10.1016/j.ydbio.2018.09.019}, pmid = {30268714}, issn = {1095-564X}, abstract = {During sexual reproduction or conjugation, ciliates form a specialized cell adhesion zone for the purpose of exchanging gametic pronuclei. Hundreds of individual membrane fusion events transform the adhesion zone into a perforated membrane curtain, the mating junction. Pronuclei from each mating partner are propelled through this fenestrated membrane junction by a web of short, cris-crossing microtubules. Pronuclear passage results in the formation of two breaches in the membrane junction. Following pronuclear exchange and karyogamy (fertilization), cells seal these twin membrane breaches thereby re-establishing cellular independence. This would seem like a straightforward problem: simply grow membrane in from the edges of each breach in a fashion similar to how animal cells "grow" their cytokinetic furrows or how plant cells construct a cell wall during mitosis. Serial section electron microscopy and 3-D electron tomography reveal that the actual mechanism is less straightforward. Each of the two membrane breaches transforms into a bowed membrane assembly platform. The resulting membrane protrusions continue to grow into the cytoplasm of the mating partner, traverse the cytoplasm in anti-parallel directions and make contact with the plasma membrane that flanks the mating junction. This investigation reveals the details of a novel, developmentally-induced mechanism of membrane disruption and restoration associated with pronuclear exchange and fertilization in the ciliate, Tetrahymena thermophila.}, } @article {pmid30268524, year = {2018}, author = {Dudney, J and Hobbs, RJ and Heilmayr, R and Battles, JJ and Suding, KN}, title = {Navigating Novelty and Risk in Resilience Management.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {863-873}, doi = {10.1016/j.tree.2018.08.012}, pmid = {30268524}, issn = {1872-8383}, abstract = {Resilience theory is increasingly applied to the management of global change impacts. There is growing concern, however, that misapplications of resilience-based management (RBM) can sometimes lead to undesirable outcomes. We address here an inescapable conundrum in the application of resilience theory: systems will need to track environmental change, but management that aims to support adaptive capacity can introduce undesirable levels of change. We provide a framework that links concepts from novel ecosystems and resilience theory to inform management of ecosystem change. We highlight that resilience-based applications need to address risks associated with novel human impacts to improve management outcomes.}, } @article {pmid30268523, year = {2018}, author = {Meiri, S and Raia, P and Santos, AMC}, title = {Anagenesis and Cladogenesis Are Useful Island Biogeography Terms.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {895-896}, doi = {10.1016/j.tree.2018.09.005}, pmid = {30268523}, issn = {1872-8383}, } @article {pmid30268405, year = {2018}, author = {Presnyakova, D and Braun, DR and Conard, NJ and Feibel, C and Harris, JWK and Pop, CM and Schlager, S and Archer, W}, title = {Site fragmentation, hominin mobility and LCT variability reflected in the early Acheulean record of the Okote Member, at Koobi Fora, Kenya.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {159-180}, doi = {10.1016/j.jhevol.2018.07.008}, pmid = {30268405}, issn = {1095-8606}, abstract = {From its initial appearance at ∼1.7 Ma, the Acheulean was prevalent through a vast chronological span of hominin behavioural evolution that lasted nearly 1.5 million years. The origins and production patterns of large bifacial cutting tools ('LCTs') - the marker of the Acheulean techno-complex - and the systematic changes in this behaviour through time are gaining increasing interest in paleoanthropology. Here we provide a synthesis of early Acheulean LCT variation in a landscape context by analysing assemblages from four different quasi-contemporaneous (∼1.4 Ma) sites from the Koobi Fora Formation. We characterize this variation using both 3D geometric morphometric and descriptive approaches. The expansive lateral exposures of fluvial and lacustrine sediments, as well as the associated tephrostratigraphy of the Koobi Fora Formation provide the landscape context that enables these comparative analyses. Our study demonstrates that when multiple contemporaneous early Acheulean localities are analysed together, a broader picture of LCT variability is elucidated. Four sites at Koobi Fora appear to represent a single system of lithic economy, characterized by a discrete trajectory of changes in LCT size and shape. These sites have ranges of LCT forms which appear to represent different but overlapping stages on a single reduction trajectory. Certain sites exhibit the full reduction trajectory while others exhibit only fragments of this trajectory. Other inter-site lithic proxies further complement these patterns in LCT variability. We explore patterns of site function, mobility and hominin landscape use, all of which may be suggestive of a depth of planning in early Acheulean hominins wherein technological activities were undertaken in substantial anticipation of future needs.}, } @article {pmid30268116, year = {2018}, author = {Alaei, SR and Abrams, CK and Bulinski, JC and Hertzberg, EL and Freidin, MM}, title = {Acetylation of C-terminal lysines modulates protein turnover and stability of Connexin-32.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {22}, pmid = {30268116}, issn = {1471-2121}, support = {R01 GM088660/GM/NIGMS NIH HHS/United States ; 1RO1GM088660/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Cell Line ; Cell Membrane/drug effects/metabolism ; Cell Proliferation/drug effects ; Connexins/*metabolism ; Gap Junctions/drug effects/metabolism ; Histone Deacetylase 6/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Lysine/*metabolism ; Protein Stability/drug effects ; Rats ; Ubiquitination/drug effects ; }, abstract = {BACKGROUND: The gap junction protein, Connexin32 (Cx32), is expressed in various tissues including liver, exocrine pancreas, gastrointestinal epithelium, and the glia of the central and peripheral nervous system. Gap junction-mediated cell-cell communication and channel-independent processes of Cx32 contribute to the regulation of physiological and cellular activities such as glial differentiation, survival, and proliferation; maintenance of the hepatic epithelium; and axonal myelination. Mutations in Cx32 cause X-linked Charcot-Marie-Tooth disease (CMT1X), an inherited peripheral neuropathy. Several CMT1X causing mutations are found in the cytoplasmic domains of Cx32, a region implicated in the regulation of gap junction assembly, turnover and function. Here we investigate the roles of acetylation and ubiquitination in the C-terminus on Cx32 protein function. Cx32 protein turnover, ubiquitination, and response to deacetylase inhibitors were determined for wild-type and C-terminus lysine mutants using transiently transfected Neuro2A (N2a) cells.

RESULTS: We report here that Cx32 is acetylated in transfected N2a cells and that inhibition of the histone deacetylase, HDAC6, results in an accumulation of Cx32. We identified five lysine acetylation targets in the C-terminus. Mutational analysis demonstrates that these lysines are involved in the regulation of Cx32 ubiquitination and turnover. While these lysines are not required for functional Cx32 mediated cell-cell communication, BrdU incorporation studies demonstrate that their relative acetylation state plays a channel-independent role in Cx32-mediated control of cell proliferation.

CONCLUSION: Taken together these results highlight the role of post translational modifications and lysines in the C-terminal tail of Cx32 in the fine-tuning of Cx32 protein stability and channel-independent functions.}, } @article {pmid30268111, year = {2018}, author = {García-Jiménez, R and Pérez-García, JM and Margalida, A}, title = {Drivers of daily movement patterns affecting an endangered vulture flight activity.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {39}, pmid = {30268111}, issn = {1472-6785}, support = {CGL2015-66966-C2-2-R//Ministerio de Economía, Industria y Competitividad, Gobierno de España/International ; FPI/BES-2016-077510//Ministerio de Economía, Industria y Competitividad, Gobierno de España/International ; FJCI-2015-25632//Ministerio de Economía, Industria y Competitividad, Gobierno de España/International ; RYC-2012-11867//Ministerio de Economía, Industria y Competitividad, Gobierno de España/International ; }, abstract = {BACKGROUND: The development of satellite tracking technology enables the gathering of huge amounts of accurate data on animal movements over measured time intervals, to reveal essential information about species' patterns of spatial use. This information is especially important in optimizing the design of conservation and management strategies for endangered species. In this study, we analysed the main drivers of daily patterns in the flight activity of the threatened Bearded Vulture Gypaetus barbatus. We studied 19 Bearded Vultures tagged with solar-powered GPS transmitters from 2006 to 2016 in the Pyrenees (Spain). We assessed the relative influence of external factors (season and daylight time) and internal factors (sex, breeding season and territorial status) on their daily activity behaviour by computing mean hourly distance travelled, maximum displacement and cumulative distance travelled per hour.

RESULTS: Our findings showed a clear difference in all the estimators between territorial and non-territorial (floating) members of the population, showing that non-territorial individuals spent much longer in flight and travelled larger distances per day. We detected an important influence of daylight time and season on the daily rhythms of Bearded Vultures; flight activity increased during the last three quarters of daylight and was greatest in the spring. Breeding period and sex had also an effect on the maximum displacement and cumulative distance travelled. Individuals flew more during the breeding period and females tended to exhibit greater cumulative and maximum distances per hour than males regardless of breeding season.

CONCLUSIONS: Pyrenean Bearded Vultures flight daily activity was strongly influenced by daylight time, season, and territorial status, while individual sex and breeding season showed a milder effect on the birds' movement behaviour. This study gives a novel insight into how external factors act as main drivers of the daily flight activity pattern of a long-lived avian scavenger.}, } @article {pmid30268095, year = {2018}, author = {Zhu, H and Liu, W and Fang, H}, title = {Inflammation caused by peripheral immune cells across into injured mouse blood brain barrier can worsen postoperative cognitive dysfunction induced by isoflurane.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {23}, pmid = {30268095}, issn = {1471-2121}, support = {2017-1//University of Texas Medical Branch (US)/International ; }, mesh = {Animals ; Blood-Brain Barrier/*immunology/*injuries/pathology ; CD4-Positive T-Lymphocytes/immunology ; Cognitive Dysfunction/*chemically induced/*physiopathology ; Disease Models, Animal ; Hippocampus/pathology ; Inflammation/*immunology ; Isoflurane/*adverse effects ; Killer Cells, Natural/immunology ; Lymphocytes/*immunology ; Male ; Mice, Inbred C57BL ; Postoperative Complications/*etiology/immunology/physiopathology ; }, abstract = {BACKGROUND: Disruption to the blood brain barrier (BBB) is a leading factor associated with the development of postoperative cognitive dysfunction (POCD). Despite this, the underlying mechanism by which BBB disruption promotes POCD in the elderly population has not yet been not fully elucidated.

RESULTS: In this study, we established a POCD mice model using isoflurane, and observed the highly expressed occludin and claudin 5 in brain tissues concomitant with the increased enrichment of CD4 positive cells and NK cells in the hippocampus of POCD mice compared to normal and non-POCD control.

CONCLUSIONS: Our data suggests that peripheral immune cells may participate in the inflammatory reaction within the hippocampus, following the administration of anesthesia via inhalation with the destruction of the blood-brain barrier.}, } @article {pmid30268093, year = {2018}, author = {Ma, Q and Yi, R and Li, L and Liang, Z and Zeng, T and Zhang, Y and Huang, H and Zhang, X and Yin, X and Cai, Z and Mu, Y and Cheng, Y and Zeng, Q and Li, X and Nian, H}, title = {GsMATE encoding a multidrug and toxic compound extrusion transporter enhances aluminum tolerance in Arabidopsis thaliana.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {212}, pmid = {30268093}, issn = {1471-2229}, support = {31771816//the National Natural Sciences Foundation of China/ ; 31371642//the National Natural Sciences Foundation of China/ ; 30971814//the National Natural Sciences Foundation of China/ ; 2016ZX08004002-007//the Major Projects of New Varieties Cultivation of Genetically Modified Organisms/ ; CARS-04-PS09//the China Agricultural Research System/ ; 6900-32990369//the Research Project of Plant Biology for Undergraduate Students of South China Agricultural University/ ; 4100-M13024//the Research Project of the State Key Laboratory of Agricultural and Biological Resources Protection and Utilization in Subtropics/ ; }, mesh = {Aluminum/*toxicity ; Arabidopsis/*drug effects/genetics ; Carrier Proteins/genetics/metabolism ; Cloning, Molecular ; Gene Expression Regulation, Plant/drug effects ; Plant Proteins/*genetics/metabolism ; Plant Roots/drug effects/genetics/metabolism ; Plants, Genetically Modified ; Soybeans/drug effects/*genetics ; }, abstract = {BACKGROUND: Multidrug and toxic compound extrusion (MATE) transporters, which exist widely in plants, function as crucial regulators in plant resistance to aluminum (Al) toxicity by inducing citrate efflux. However, the functions of most MATE family members in soybean (Glycine soja) remain to be elucidated.

RESULTS: Expression pattern analysis showed that GsMATE was constitutively expressed in different soybean organs, with the highest level in root compared with those in stem, leaf and cotyledon. In addition, Al stress induced expression of GsMATE in soybean. Temporal analysis indicated that GsMATE expression was greatly enhanced by increasing concentrations of aluminum [Al3+] after short exposure, reaching the high levels detected in the BW69 (Al-resistant) and the JW81 (Al-sensitive) lines of Glycine soja of wild soybean at 6 h and 8 h, respectively. Furthermore, transient GsMATE expression in Arabidopsis protoplasts showed that GsMATE protein localized to the plasma membrane. Overexpression of GsMATE on an Arabidopsis columbia-0 (Col-0) background resulted in increased Al tolerance in transgenic plants. Analysis of hematoxylin staining showed that the roots of GsMATE transgenic lines were stained less intensely than those of the wild-type exposured to the same AlCl3 concentrations. Therefore, GsMATE enhanced the resistance of transgenic plants to Al toxicity by reducing Al accumulation in Arabidopsis roots.

CONCLUSIONS: In summary, our results indicate that GsMATE is responsive to aluminum stress and may participate in the regulation of sensitivity to Al toxicity in Arabidopsis. In addition, the GsMATE protein is an Al-induced citrate transporter of the MATE family and exerts an essential role in Al tolerance in Glycine soja.}, } @article {pmid30268091, year = {2018}, author = {Sambo, F and Finotello, F and Lavezzo, E and Baruzzo, G and Masi, G and Peta, E and Falda, M and Toppo, S and Barzon, L and Di Camillo, B}, title = {Optimizing PCR primers targeting the bacterial 16S ribosomal RNA gene.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {343}, pmid = {30268091}, issn = {1471-2105}, mesh = {Bacteria/*genetics ; DNA Primers/genetics/*standards ; Polymerase Chain Reaction/*standards ; RNA, Bacterial/*genetics ; RNA, Ribosomal, 16S/*genetics ; *Software ; }, abstract = {BACKGROUND: Targeted amplicon sequencing of the 16S ribosomal RNA gene is one of the key tools for studying microbial diversity. The accuracy of this approach strongly depends on the choice of primer pairs and, in particular, on the balance between efficiency, specificity and sensitivity in the amplification of the different bacterial 16S sequences contained in a sample. There is thus the need for computational methods to design optimal bacterial 16S primers able to take into account the knowledge provided by the new sequencing technologies.

RESULTS: We propose here a computational method for optimizing the choice of primer sets, based on multi-objective optimization, which simultaneously: 1) maximizes efficiency and specificity of target amplification; 2) maximizes the number of different bacterial 16S sequences matched by at least one primer; 3) minimizes the differences in the number of primers matching each bacterial 16S sequence. Our algorithm can be applied to any desired amplicon length without affecting computational performance. The source code of the developed algorithm is released as the mopo16S software tool (Multi-Objective Primer Optimization for 16S experiments) under the GNU General Public License and is available at http://sysbiobig.dei.unipd.it/?q=Software#mopo16S .

CONCLUSIONS: Results show that our strategy is able to find better primer pairs than the ones available in the literature according to all three optimization criteria. We also experimentally validated three of the primer pairs identified by our method on multiple bacterial species, belonging to different genera and phyla. Results confirm the predicted efficiency and the ability to maximize the number of different bacterial 16S sequences matched by primers.}, } @article {pmid30268090, year = {2018}, author = {Fu, D and Ortega-Hernández, J and Daley, AC and Zhang, X and Shu, D}, title = {Anamorphic development and extended parental care in a 520 million-year-old stem-group euarthropod from China.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {147}, pmid = {30268090}, issn = {1471-2148}, mesh = {Animals ; Arthropods/anatomy & histology/classification/*growth & development ; China ; *Fossils ; Time Factors ; }, abstract = {BACKGROUND: Extended parental care is a complex reproductive strategy in which progenitors actively look after their offspring up to - or beyond - the first juvenile stage in order to maximize their fitness. Although the euarthropod fossil record has produced several examples of brood-care, the appearance of extended parental care within this phylum remains poorly constrained given the scarcity of developmental data for Palaeozoic stem-group representatives that would link juvenile and adult forms in an ontogenetic sequence.

RESULTS: Here, we describe the post-embryonic growth of Fuxianhuia protensa from the early Cambrian Chengjiang Lagerstätte in South China. Our data demonstrate anamorphic post-embryonic development for F. protensa, in which new tergites were sequentially added from a posterior growth zone, the number of tergites varies from eight to 30. The growth of F. protensa is typified by the alternation between segment addition, followed by the depletion of the anteriormost abdominal segment into the thoracic region. The transformation of abdominal into thoracic tergite is demarcated by the development of laterally tergopleurae, and biramous walking legs. The new ontogeny data leads to the recognition of the rare Chengjiang euarthropod Pisinnocaris subconigera as a junior synonym of Fuxianhuia. Comparisons between different species of Fuxianhuia and with other genera within Fuxianhuiida suggest that heterochrony played a prominent role in the morphological diversification of fuxianhuiids. Functional analogy with the flexible trunk ontogeny of Cambrian and Silurian olenimorphic trilobites suggests an adaptation to sporadic low oxygen conditions in Chengjiang deposits for F. protensa. Finally, understanding the growth of F. protensa allows for the interpretation of an exceptional life assemblage consisting of a sexually mature adult alongside four ontogenetically coeval juveniles, which constitutes the oldest occurrence of extended parental care by prolonged cohabitation in the panarthropod fossil record.

CONCLUSIONS: Our findings constitute the most detailed characterization of the post-embryonic development in a soft-bodied upper stem-group euarthropod available to date. The new ontogeny data illuminates the systematics, trunk segmentation and palaeoecology of F. protensa, offers insights on the macroevolutionary processes involved in the diversification of this clade, and contributes towards an improved understanding of complex post-embryonic reproductive ecology in Cambrian euarthropods.}, } @article {pmid30268089, year = {2018}, author = {Luo, TJ and Zhou, CL and Chao, F}, title = {Exploring spatial-frequency-sequential relationships for motor imagery classification with recurrent neural network.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {344}, pmid = {30268089}, issn = {1471-2105}, support = {61673326//National Natural Science Foundation of China/ ; 61673322//National Natural Science Foundation of China/ ; 20720160126//Fundamental Research Funds for the Central Universities/ ; 2017J01128//Natural Science Foundation of Fujian Province of China/ ; 2017J01129//Natural Science Foundation of Fujian Province of China/ ; 663830//European Union's Horizon 2020 research and innovation programme/ ; 91746103//National Natural Science Foundation of China (CN)/ ; }, mesh = {Algorithms ; *Brain-Computer Interfaces ; Databases, Genetic ; Datasets as Topic ; Electroencephalography/*classification/*methods ; Humans ; Imagination/*physiology ; *Neural Networks (Computer) ; *Signal Processing, Computer-Assisted ; Support Vector Machine ; }, abstract = {BACKGROUND: Conventional methods of motor imagery brain computer interfaces (MI-BCIs) suffer from the limited number of samples and simplified features, so as to produce poor performances with spatial-frequency features and shallow classifiers.

METHODS: Alternatively, this paper applies a deep recurrent neural network (RNN) with a sliding window cropping strategy (SWCS) to signal classification of MI-BCIs. The spatial-frequency features are first extracted by the filter bank common spatial pattern (FB-CSP) algorithm, and such features are cropped by the SWCS into time slices. By extracting spatial-frequency-sequential relationships, the cropped time slices are then fed into RNN for classification. In order to overcome the memory distractions, the commonly used gated recurrent unit (GRU) and long-short term memory (LSTM) unit are applied to the RNN architecture, and experimental results are used to determine which unit is more suitable for processing EEG signals.

RESULTS: Experimental results on common BCI benchmark datasets show that the spatial-frequency-sequential relationships outperform all other competing spatial-frequency methods. In particular, the proposed GRU-RNN architecture achieves the lowest misclassification rates on all BCI benchmark datasets.

CONCLUSION: By introducing spatial-frequency-sequential relationships with cropping time slice samples, the proposed method gives a novel way to construct and model high accuracy and robustness MI-BCIs based on limited trials of EEG signals.}, } @article {pmid30268088, year = {2018}, author = {Trobajo-Sanmartín, C and Ezpeleta, G and Pais, C and Eraso, E and Quindós, G}, title = {Design and validation of a multiplex PCR protocol for microsatellite typing of Candida parapsilosis sensu stricto isolates.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {718}, pmid = {30268088}, issn = {1471-2164}, mesh = {Candida parapsilosis/*classification/genetics/isolation & purification ; Candidiasis, Invasive/diagnosis ; DNA, Fungal/analysis ; Genotyping Techniques ; Humans ; *Microsatellite Repeats ; Multiplex Polymerase Chain Reaction/methods ; Mycological Typing Techniques/*methods ; Sensitivity and Specificity ; }, abstract = {BACKGROUND: Analysis of polymorphic microsatellite markers (STR) is a helpful genotyping technique to differentiate Candida parapsilosis sensu stricto isolates. The aim of this study is to develop and perform an initial validation of an alternative protocol for the reliable and accurate microsatellite genotyping of C. parapsilosis sensu stricto isolates using high-throughput multiplex PCR. To achieve this, the results obtained using the new protocol were compared to the ones obtained using a previously described reference method. To that end, diagnostic accuracy, informativeness and discrimination parameters were estimated.

RESULTS: Our results showed good concordance between both methods (Kappa index: 0.920), leading to a high sensitivity (1; CI(95%) (0.991-1)) and specificity (1; CI(95%) (0.772-1)) after the validation of the new protocol. Moreover, the electropherograms profiles obtained with the new PCR scheme showed a high signal to noise ratio (SNR).

CONCLUSIONS: The new multiplex protocol is valuable for the differentiation of C. parapsilosis sensu stricto, with direct clinical applications. Besides, the new protocol represents a shortening the hands-on time, reducing the sample manipulation (dismissing the possibility of cross-contamination), maintaining the quality of the results (when compared to the ones obtained with the reference method), and helping to the standardization and simplification of the genotyping scheme.}, } @article {pmid30267554, year = {2018}, author = {Macartney, EL and Nicovich, PR and Bonduriansky, R and Crean, AJ}, title = {Developmental diet irreversibly shapes male post-copulatory traits in the neriid fly Telostylinus angusticollis.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1894-1902}, doi = {10.1111/jeb.13384}, pmid = {30267554}, issn = {1420-9101}, support = {//Australian Research Council/ ; }, abstract = {Nutrient availability has been shown to influence investment in many fitness-related traits, including male reproductive success. Many studies have demonstrated that a reduction in nutrient availability alters male post-copulatory trait expression, with some studies demonstrating an effect of developmental nutrients and others, an effect of adult nutrients. However, few studies have manipulated both developmental and adult nutrients in the same experiment. Therefore, it is not clear what life-stage has the greatest effect on post-copulatory trait expression, and if the effects of developmental and adult nutrients can interact. Here, we investigate effects of developmental and adult nutrition on male testes and accessory gland size, sperm movement within the female reproductive tract and sperm length in the neriid fly, Telostylinus angusticollis. We found that males fed a nutrient-poor developmental diet produced sperm with a reduced tail beat frequency and had smaller testes and accessory glands compared to males fed a nutrient-rich developmental diet. In contrast, we found no effects of adult nutrition on any traits measured, although sperm length was correlated with body size and male age but unaffected by nutrition at any stage. Therefore, investment in adult post-copulatory traits is determined early on by developmental nutrients in male neriid flies, and this effect is not altered by adult nutrient availability.}, } @article {pmid30267552, year = {2018}, author = {Amir, M and Kumar, V and Dohare, R and Islam, A and Ahmad, F and Hassan, MI}, title = {Sequence, structure and evolutionary analysis of cold shock domain proteins, a member of OB fold family.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1903-1917}, doi = {10.1111/jeb.13382}, pmid = {30267552}, issn = {1420-9101}, support = {//Department of Science and Technology, India/ ; //Council of Scientific & Industrial Research (CSIR)/ ; }, abstract = {The cold shock domain (CSD) belongs to the oligosaccharide/oligonucleotide-binding fold superfamily which is highly conserved from prokaryotes to higher eukaryotes, and appears to function as RNA chaperones. CSD is involved in diverse cellular processes, including adaptation to low temperatures, nutrient stress, cellular growth and developmental processes. Structural Classification of Proteins (SCOP) database broadly classifies OB fold proteins into 18 different superfamilies, including nucleic acid-binding superfamily (NAB). The NAB is further divided into 17 families together with cold shock DNA-binding protein family (CSDB). The CSDB have more than 240 000 sequences in UniProt database consisting of 32 domains including CSD. Among these domains, CSD is the second largest sequence contributor (> 40 398 sequences). Herein, we have systematically analysed the relative abundance and distribution of CSD proteins based on sequences, structures, repeats and gene ontology (GO) molecular functions in all domains of life. Analysis of sequence distribution suggesting that CSDs are largely found in bacteria (83-94%) with single CSD repeat. However, repeat distribution in eukaryota varies from 1 to 5 in combination with other auxiliary domain that makes CSD proteins functionally more diverse compared to the bacterial counterparts. Further, analysis of repeats distributions on evolutionary scale suggest that existence of CSD in multiple repeats is mainly driven through speciation, gene shuffling and gene duplication events.}, } @article {pmid30267420, year = {2018}, author = {Sheth, SN and Kulbaba, MW and Pain, RE and Shaw, RG}, title = {Expression of additive genetic variance for fitness in a population of partridge pea in two field sites.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2537-2545}, doi = {10.1111/evo.13614}, pmid = {30267420}, issn = {1558-5646}, support = {DEB 1257462//National Science Foundation/ ; 1016272//National Institute of Food and Agriculture/ ; 1257462//Division of Environmental Biology/ ; 1523866//Division of Biological Infrastructure/ ; }, abstract = {Despite the importance of adaptation in shaping biological diversity over many generations, little is known about populations' capacities to adapt at any particular time. Theory predicts that a population's rate of ongoing adaptation is the ratio of its additive genetic variance for fitness, V A (W) , to its mean absolute fitness, W ¯ . We conducted a transplant study to quantify W ¯ and standing V A (W) for a population of the annual legume Chamaecrista fasciculata in one field site from which we initially sampled it and another site where it does not currently occur naturally. We also examined genotype-by-environment interactions, G × E, as well as its components, differences between sites in V A (W) and in rank of breeding values for fitness. The mean fitness indicated population persistence in both sites, and there was substantial V A (W) for ongoing adaptation at both sites. Statistically significant G × E indicated that the adaptive process would differ between sites. We found a positive correlation between fitness of genotypes in the "home" and "away" environments, and G × E was more pronounced as the life-cycle proceeds. This study exemplifies an approach to assessing whether there is sufficient V A (W) to support evolutionary rescue in populations that are declining.}, } @article {pmid30267141, year = {2018}, author = {Detheridge, AP and Griffith, GW and Hopper, DJ}, title = {Genome Sequence Analysis of Two Pseudomonas putida Strains to Identify a 17-Hydroxylase Putatively Involved in Sparteine Degradation.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1649-1654}, pmid = {30267141}, issn = {1432-0991}, mesh = {Alkaloids/genetics ; Bacterial Proteins/*genetics ; Genome, Bacterial/*genetics ; Oxidoreductases Acting on CH-NH Group Donors/genetics ; Pseudomonas putida/*genetics ; Sequence Analysis/methods ; Sparteine/analogs & derivatives/*genetics ; Steroid 17-alpha-Hydroxylase/*genetics ; Whole Genome Sequencing/methods ; }, abstract = {Two strains of Pseudomonas putida, Psp-LUP and Psp-SPAR, capable of growth on the quinolizidine alkaloids, lupanine and sparteine respectively, were studied here. We report the isolation of Psp-SPAR and the complete genome sequencing of both bacteria. Both were confirmed to belong to P. putida, Psp-LUP close to the type isolate of the species (NBRC14164T) and Psp-SPAR close to strains KT2440 and F1. Psp-SPAR did not grow on lupanine but did contain a gene encoding a putative quinolizidine-17-hydroxylase peptide which exhibited high similarity (76%identity) to the lupanine-17-hydroxylase characterised from Psp-LUP.}, } @article {pmid30267031, year = {2018}, author = {Winters, IP and Murray, CW and Winslow, MM}, title = {Towards quantitative and multiplexed in vivo functional cancer genomics.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {12}, pages = {741-755}, doi = {10.1038/s41576-018-0053-7}, pmid = {30267031}, issn = {1471-0064}, abstract = {Large-scale sequencing of human tumours has uncovered a vast array of genomic alterations. Genetically engineered mouse models recapitulate many features of human cancer and have been instrumental in assigning biological meaning to specific cancer-associated alterations. However, their time, cost and labour-intensive nature limits their broad utility; thus, the functional importance of the majority of genomic aberrations in cancer remains unknown. Recent advances have accelerated the functional interrogation of cancer-associated alterations within in vivo models. Specifically, the past few years have seen the emergence of CRISPR-Cas9-based strategies to rapidly generate increasingly complex somatic alterations and the development of multiplexed and quantitative approaches to ascertain gene function in vivo.}, } @article {pmid30266994, year = {2018}, author = {York, A}, title = {Exploiting peroxisomes.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {659}, doi = {10.1038/s41579-018-0095-z}, pmid = {30266994}, issn = {1740-1534}, } @article {pmid30266993, year = {2018}, author = {York, A}, title = {Stronger together.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {659}, doi = {10.1038/s41579-018-0096-y}, pmid = {30266993}, issn = {1740-1534}, } @article {pmid30266795, year = {2018}, author = {Hedges, SB and Tao, Q and Walker, M and Kumar, S}, title = {Accurate timetrees require accurate calibrations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9510-E9511}, pmid = {30266795}, issn = {1091-6490}, support = {R01 GM126567/GM/NIGMS NIH HHS/United States ; }, mesh = {Calibration ; *Fossils ; *Phylogeny ; }, } @article {pmid30266794, year = {2018}, author = {Morris, JL and Puttick, MN and Clark, JW and Edwards, D and Kenrick, P and Pressel, S and Wellman, CH and Yang, Z and Schneider, H and Donoghue, PCJ}, title = {Reply to Hedges et al.: Accurate timetrees do indeed require accurate calibrations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9512-E9513}, pmid = {30266794}, issn = {1091-6490}, mesh = {*Biological Evolution ; Calibration ; Fossils ; Phylogeny ; *Plants ; }, } @article {pmid30266793, year = {2018}, author = {Zhu, H and Xie, W and Xu, D and Miki, D and Tang, K and Huang, CF and Zhu, JK}, title = {DNA demethylase ROS1 negatively regulates the imprinting of DOGL4 and seed dormancy in Arabidopsis thaliana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9962-E9970}, pmid = {30266793}, issn = {1091-6490}, mesh = {Arabidopsis/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; *DNA Methylation ; DNA, Plant/genetics ; DNA-Binding Proteins/genetics/*metabolism ; Epigenesis, Genetic ; Gene Expression Regulation, Plant ; *Genomic Imprinting ; Nuclear Proteins/genetics/*metabolism ; *Plant Dormancy ; Seeds/*physiology ; Transcription Factors/genetics/*metabolism ; }, abstract = {Genomic imprinting is a form of epigenetic regulation resulting in differential gene expression that reflects the parent of origin. In plants, imprinted gene expression predominantly occurs in the seed endosperm. Maternal-specific DNA demethylation by the DNA demethylase DME frequently underlies genomic imprinting in endosperm. Whether other more ubiquitously expressed DNA demethylases regulate imprinting is unknown. Here, we found that the DNA demethylase ROS1 regulates the imprinting of DOGL4DOGL4 is expressed from the maternal allele in endosperm and displays preferential methylation and suppression of the paternal allele. We found that ROS1 negatively regulates imprinting by demethylating the paternal allele, preventing its hypermethylation and complete silencing. Furthermore, we found that DOGL4 negatively affects seed dormancy and response to the phytohormone abscisic acid and that ROS1 controls these processes by regulating DOGL4 Our results reveal roles for ROS1 in mitigating imprinted gene expression and regulating seed dormancy.}, } @article {pmid30266792, year = {2018}, author = {Lukhtanov, VA and Dincă, V and Friberg, M and Šíchová, J and Olofsson, M and Vila, R and Marec, F and Wiklund, C}, title = {Versatility of multivalent orientation, inverted meiosis, and rescued fitness in holocentric chromosomal hybrids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9610-E9619}, pmid = {30266792}, issn = {1091-6490}, mesh = {Animals ; *Butterflies/genetics/metabolism ; *Chimera/genetics/metabolism ; *Chromatids/genetics/metabolism ; Chromosomes, Insect/genetics/metabolism ; Metaphase/*physiology ; }, abstract = {Chromosomal rearrangements (e.g., fusions/fissions) have the potential to drive speciation. However, their accumulation in a population is generally viewed as unlikely, because chromosomal heterozygosity should lead to meiotic problems and aneuploid gametes. Canonical meiosis involves segregation of homologous chromosomes in meiosis I and sister chromatid segregation during meiosis II. In organisms with holocentric chromosomes, which are characterized by kinetic activity distributed along almost the entire chromosome length, this order may be inverted depending on their metaphase I orientation. Here we analyzed the evolutionary role of this intrinsic versatility of holocentric chromosomes, which is not available to monocentric ones, by studying F1 to F4 hybrids between two chromosomal races of the Wood White butterfly (Leptidea sinapis), separated by at least 24 chromosomal fusions/fissions. We found that these chromosomal rearrangements resulted in multiple meiotic multivalents, and, contrary to the theoretical prediction, the hybrids displayed relatively high reproductive fitness (42% of that of the control lines) and regular behavior of meiotic chromosomes. In the hybrids, we also discovered inverted meiosis, in which the first and critical stage of chromosome number reduction was replaced by the less risky stage of sister chromatid separation. We hypothesize that the ability to invert the order of the main meiotic events facilitates proper chromosome segregation and hence rescues fertility and viability in chromosomal hybrids, potentially promoting dynamic karyotype evolution and chromosomal speciation.}, } @article {pmid30266791, year = {2018}, author = {Cira, NJ and Pearce, MT and Quake, SR}, title = {Neutral and selective dynamics in a synthetic microbial community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9842-E9848}, pmid = {30266791}, issn = {1091-6490}, mesh = {*Biodiversity ; *Ecosystem ; Microbial Consortia/*physiology ; *Models, Theoretical ; *Population Dynamics ; Species Specificity ; }, abstract = {Ecologists debate the relative importance of selective vs. neutral processes in understanding biodiversity. This debate is especially pertinent to microbial communities, which play crucial roles in areas such as health, disease, industry, and the environment. Here, we created a synthetic microbial community using heritable genetic barcodes and tracked community composition over repeated rounds of subculture with immigration. Consistent with theory, we find a transition exists between neutral and selective regimes, and the crossover point depends on the fraction of immigrants and the magnitude of fitness differences. Neutral models predict an increase in diversity with increased carrying capacity, while our selective model predicts a decrease in diversity. The community here lost diversity with an increase in carrying capacity, highlighting that using the correct model is essential for predicting community response to change. Together, these results emphasize the importance of including selection to obtain realistic models of even simple systems.}, } @article {pmid30266790, year = {2018}, author = {Katzelnick, LC and Ben-Shachar, R and Mercado, JC and Rodriguez-Barraquer, I and Elizondo, D and Arguello, S and Nuñez, A and Ojeda, S and Sanchez, N and Lopez Mercado, B and Gresh, L and Burger-Calderon, R and Kuan, G and Gordon, A and Balmaseda, A and Harris, E}, title = {Dynamics and determinants of the force of infection of dengue virus from 1994 to 2015 in Managua, Nicaragua.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10762-10767}, pmid = {30266790}, issn = {1091-6490}, support = {R42 AI062100/AI/NIAID NIH HHS/United States ; P01 AI106695/AI/NIAID NIH HHS/United States ; R41 AI062100/AI/NIAID NIH HHS/United States ; U54 AI065359/AI/NIAID NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; R01 AI099631/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Antibodies, Viral/*blood ; Child ; Child, Preschool ; Dengue/*epidemiology/*transmission/virology ; Dengue Virus/*isolation & purification ; Female ; Humans ; Male ; Nicaragua/epidemiology ; Prospective Studies ; Public Health Surveillance ; *Seroepidemiologic Studies ; Time Factors ; }, abstract = {Dengue virus (DENV) is the most prevalent human vector-borne viral disease. The force of infection (FoI), the rate at which susceptible individuals are infected in a population, is an important metric for infectious disease modeling. Understanding how and why the FoI of DENV changes over time is critical for developing immunization and vector control policies. We used age-stratified seroprevalence data from 12 years of the Pediatric Dengue Cohort Study in Nicaragua to estimate the annual FoI of DENV from 1994 to 2015. Seroprevalence data revealed a change in the rate at which children acquire DENV-specific immunity: in 2004, 50% of children age >4 years were seropositive, but by 2015, 50% seropositivity was reached only by age 11 years. We estimated a spike in the FoI in 1997-1998 and 1998-1999 and a gradual decline thereafter, and children age <4 years experienced a lower FoI. Two hypotheses to explain the change in the FoI were tested: (i) a transition from introduction of specific DENV serotypes to their endemic transmission and (ii) a population demographic transition due to declining birth rates and increasing life expectancy. We used mathematical models to simulate these hypotheses. We show that the initial high FoI can be explained by the introduction of DENV-3 in 1994-1998, and that the overall gradual decline in the FoI can be attributed to demographic shifts. Changes in immunity and demographics strongly impacted DENV transmission in Nicaragua. Population-level measures of transmission intensity are dynamic and thus challenging to use to guide vaccine implementation locally and globally.}, } @article {pmid30266789, year = {2018}, author = {Choi, BK and Dayaram, T and Parikh, N and Wilkins, AD and Nagarajan, M and Novikov, IB and Bachman, BJ and Jung, SY and Haas, PJ and Labrie, JL and Pickering, CR and Adikesavan, AK and Regenbogen, S and Kato, L and Lelescu, A and Buchovecky, CM and Zhang, H and Bao, SH and Boyer, S and Weber, G and Scott, KL and Chen, Y and Spangler, S and Donehower, LA and Lichtarge, O}, title = {Literature-based automated discovery of tumor suppressor p53 phosphorylation and inhibition by NEK2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10666-10671}, pmid = {30266789}, issn = {1091-6490}, support = {R01 GM079656/GM/NIGMS NIH HHS/United States ; T32 HD007495/HD/NICHD NIH HHS/United States ; U54 HD007495/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; T32 GM008307/GM/NIGMS NIH HHS/United States ; P30 HD007495/HD/NICHD NIH HHS/United States ; }, mesh = {*Abstracting and Indexing as Topic ; HCT116 Cells ; HEK293 Cells ; Humans ; NIMA-Related Kinases/genetics/*metabolism ; Natural Language Processing ; Phosphorylation ; PubMed ; Tumor Suppressor Protein p53/*antagonists & inhibitors/genetics/*metabolism ; }, abstract = {Scientific progress depends on formulating testable hypotheses informed by the literature. In many domains, however, this model is strained because the number of research papers exceeds human readability. Here, we developed computational assistance to analyze the biomedical literature by reading PubMed abstracts to suggest new hypotheses. The approach was tested experimentally on the tumor suppressor p53 by ranking its most likely kinases, based on all available abstracts. Many of the best-ranked kinases were found to bind and phosphorylate p53 (P value = 0.005), suggesting six likely p53 kinases so far. One of these, NEK2, was studied in detail. A known mitosis promoter, NEK2 was shown to phosphorylate p53 at Ser315 in vitro and in vivo and to functionally inhibit p53. These bona fide validations of text-based predictions of p53 phosphorylation, and the discovery of an inhibitory p53 kinase of pharmaceutical interest, suggest that automated reasoning using a large body of literature can generate valuable molecular hypotheses and has the potential to accelerate scientific discovery.}, } @article {pmid30266460, year = {2019}, author = {Feng, Y and Comes, HP and Zhou, XP and Qiu, YX}, title = {Phylogenomics recovers monophyly and early Tertiary diversification of Dipteronia (Sapindaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {9-17}, doi = {10.1016/j.ympev.2018.09.012}, pmid = {30266460}, issn = {1095-9513}, abstract = {Dipteronia (Sapindaceae) is an ancient relict woody genus, and contains just two extant species endemic to Southwestern and Central China. As sharing numerous morphological characters, Dipteronia and Acer have long been considered as sister groups forming the traditional family Aceraceae. However, molecular phylogenetics has generally not resolved the phylogenetic placement of Dipteronia, especially not in its expected position as sister to Acer. In this study, we present large-scale, phylogenomic data sets, incorporating complete chloroplast (cp) genome sequences and transcriptome data from 13 Sapindaceae species, to resolve the phylogenetic relationship between Dipteronia and Acer. Moreover, the impact of long-branch attraction (LBA) artefacts and robustness of inferred topologies are assessed by long-branch excluding and coalescent-based methods. Corroborating classical morphology-based classifications, both cp genome and nuclear datasets (2466 co-orthologous genes and 273 co-SCNGs) recover Dipteronia and Acer as mutually monophyletic groups. In addition, our fossil-calibrated molecular phylogenies date the crown of the two extant Dipteronia species to the Paleocene/Eocene boundary, implying that these morphologically highly similar taxa are amongst the oldest 'living fossils' of the East Asian Flora.}, } @article {pmid30266459, year = {2019}, author = {Nakada, T and Tsuchida, Y and Tomita, M}, title = {Improved taxon sampling and multigene phylogeny of unicellular chlamydomonads closely related to the colonial volvocalean lineage Tetrabaenaceae-Goniaceae-Volvocaceae (Volvocales, Chlorophyceae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {1-8}, doi = {10.1016/j.ympev.2018.09.013}, pmid = {30266459}, issn = {1095-9513}, abstract = {In the green algal order Volvocales (Chlorophyceae), flagellate colonial forms have evolved at least four times. One of these colonial lineages, Tetrabaenaceae-Goniaceae-Volvocaceae (TGV), which belongs to the clade Reinhardtinia, is closely related to several unicellular chlamydomonads in the genera Chlamydomonas and Vitreochlamys. However, the unicellular sister of TGV has not been specified. Here, the largest ever 18S rRNA phylogenetic tree of Reinhardtinia was constructed including several newly isolated chlamydomonads, and a clade (core-Reinhardtinia) including 32 unicellular lineages and three colonial families were recognized. Interrelationships within core-Reinhardtinia were barely resolved in the tree, and therefore combined 18S-atpB-psaA-psaB-psbC-rbcL gene phylogenetic analyses were performed with selected representatives of 29 of the 32 unicellular lineages and three colonial families. The 29 unicellular lineages were clustered into five metaclades and an unassigned lineage; the metaclade that includes Chlamydomonas pila was resolved, with moderate support, as the sister clade to TGV. To examine possible biases from specific gene(s), long-branch taxa, and the heterogeneous base composition, phylogenetic analyses using several smaller data sets were also performed. Light microscopy of C. pila and its relatives indicated that any early steps towards colony evolution appeared after divergence of TGV from the C. pila lineage.}, } @article {pmid30266447, year = {2018}, author = {Iritani, R and Sato, T}, title = {Host-Manipulation by Trophically Transmitted Parasites: The Switcher-Paradigm.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {934-944}, doi = {10.1016/j.pt.2018.08.005}, pmid = {30266447}, issn = {1471-5007}, abstract = {Host-manipulation by trophically transmitted parasites is thought to always predispose the intermediate hosts to enhanced predation by definitive hosts ('enhancement'). However, theory predicts that enhancement can disrupt stable, bottom-heavy predator-prey ratios, leading to fluctuation-driven extinction of intermediate hosts and parasites. How then can enhancement persist in nature despite this apparent instability? We address this paradox and conceptualize the 'switcher-paradigm', a novel framework incorporating sequential phases of reduced predation ('suppression') followed by enhancement. Theoretical models within the framework that consider 'switching' from suppression to enhancement indicate that switching likely increases parasite persistence and, in some circumstances, cancels out the effects of strong enhancement, leading to bottom-heavy predator-prey ratios. The switcher-paradigm confronts interdisciplinary research challenges, linking ecological processes across scales from within-host to community-wide dynamics.}, } @article {pmid30266259, year = {2018}, author = {Yaguchi, J and Yamazaki, A and Yaguchi, S}, title = {Meis transcription factor maintains the neurogenic ectoderm and regulates the anterior-posterior patterning in embryos of a sea urchin, Hemicentrotus pulcherrimus.}, journal = {Developmental biology}, volume = {444}, number = {1}, pages = {1-8}, doi = {10.1016/j.ydbio.2018.09.018}, pmid = {30266259}, issn = {1095-564X}, abstract = {Precise body axis formation is an essential step in the development of multicellular organisms, for most of which the molecular gradient and/or specifically biased localization of cell-fate determinants in eggs play important roles. In sea urchins, however, any biased proteins and mRNAs have not yet been identified in the egg except for vegetal cortex molecules, suggesting that sea urchin development is mostly regulated by uniformly distributed maternal molecules with contributions to axis formation that are not well characterized. Here, we describe that the maternal Meis transcription factor regulates anterior-posterior axis formation through maintenance of the most anterior territory in embryos of a sea urchin, Hemicentrotus pulcherrimus. Loss-of-function experiments revealed that Meis is intrinsically required for maintenance of the anterior neuroectoderm specifier foxQ2 after hatching and, consequently, the morphant lost anterior neuroectoderm characteristics. In addition, the expression patterns of univin and VEGF, the lateral ectoderm markers, and the mesenchyme-cell pattern shifted toward the anterior side in Meis morphants more than they did in control embryos, indicating that Meis contributes to the precise anteroposterior patterning by regulating the anterior neuroectodermal fate.}, } @article {pmid30266244, year = {2018}, author = {Miller, ET and Svanbäck, R and Bohannan, BJM}, title = {Microbiomes as Metacommunities: Understanding Host-Associated Microbes through Metacommunity Ecology.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {926-935}, doi = {10.1016/j.tree.2018.09.002}, pmid = {30266244}, issn = {1872-8383}, support = {P50 GM098911/GM/NIGMS NIH HHS/United States ; }, abstract = {Interest in host-associated microbiomes has skyrocketed recently, yet our ability to explain microbiome variation has remained stubbornly low. Considering scales of interaction beyond the level of the individual host could lead to new insights. Metacommunity theory has many of the tools necessary for modeling multiscale processes and has been successfully applied to host microbiomes. However, the biotic nature of the host requires an expansion of theory to incorporate feedback between the habitat patch (host) and their local (microbial) community. This feedback can have unexpected effects, is predicted to be common, and can arise through a variety of mechanisms, including developmental, ecological, and evolutionary processes. We propose a new way forward for both metacommunity theory and host microbiome research that incorporates this feedback.}, } @article {pmid30266243, year = {2018}, author = {Emerson, BC and Patiño, J}, title = {Babies, Bathwater, and Straw Men? Not Quite: A Response to Meiri et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {12}, pages = {896-897}, doi = {10.1016/j.tree.2018.09.004}, pmid = {30266243}, issn = {1872-8383}, } @article {pmid30266101, year = {2018}, author = {Alneberg, J and Karlsson, CMG and Divne, AM and Bergin, C and Homa, F and Lindh, MV and Hugerth, LW and Ettema, TJG and Bertilsson, S and Andersson, AF and Pinhassi, J}, title = {Genomes from uncultivated prokaryotes: a comparison of metagenome-assembled and single-amplified genomes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {173}, pmid = {30266101}, issn = {2049-2618}, support = {310039//European Research Council/International ; }, abstract = {BACKGROUND: Prokaryotes dominate the biosphere and regulate biogeochemical processes essential to all life. Yet, our knowledge about their biology is for the most part limited to the minority that has been successfully cultured. Molecular techniques now allow for obtaining genome sequences of uncultivated prokaryotic taxa, facilitating in-depth analyses that may ultimately improve our understanding of these key organisms.

RESULTS: We compared results from two culture-independent strategies for recovering bacterial genomes: single-amplified genomes and metagenome-assembled genomes. Single-amplified genomes were obtained from samples collected at an offshore station in the Baltic Sea Proper and compared to previously obtained metagenome-assembled genomes from a time series at the same station. Among 16 single-amplified genomes analyzed, seven were found to match metagenome-assembled genomes, affiliated with a diverse set of taxa. Notably, genome pairs between the two approaches were nearly identical (average 99.51% sequence identity; range 98.77-99.84%) across overlapping regions (30-80% of each genome). Within matching pairs, the single-amplified genomes were consistently smaller and less complete, whereas the genetic functional profiles were maintained. For the metagenome-assembled genomes, only on average 3.6% of the bases were estimated to be missing from the genomes due to wrongly binned contigs.

CONCLUSIONS: The strong agreement between the single-amplified and metagenome-assembled genomes emphasizes that both methods generate accurate genome information from uncultivated bacteria. Importantly, this implies that the research questions and the available resources are allowed to determine the selection of genomics approach for microbiome studies.}, } @article {pmid30266099, year = {2018}, author = {Rath, S and Rud, T and Karch, A and Pieper, DH and Vital, M}, title = {Pathogenic functions of host microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {174}, pmid = {30266099}, issn = {2049-2618}, abstract = {BACKGROUND: It is becoming evident that certain features of human microbiota, encoded by distinct autochthonous taxa, promote disease. As a result, borders between the so-called opportunistic pathogens, pathobionts, and commensals are increasingly blurred, and specific targets for manipulating microbiota to improve host health are becoming elusive.

RESULTS: In this study, we focus on the functions of host bacterial communities that have the potential to cause disease, proposing the term "pathogenic function (pathofunction)". The concept is presented via three distinct examples, namely, the formation of (i) trimethylamine, (ii) secondary bile acids, and (iii) hydrogen sulfide, which represent metabolites of the gut microbiota linked to the development of non-communicable diseases. Using publicly available metagenomic and metatranscriptomic data (n = 2975), we quantified those pathofunctions in health and disease and exposed the key players. Pathofunctions were ubiquitously present with increased abundances in patient groups. Overall, the three pathofunctions were detected at low mean concentrations (< 1% of total bacteria carried respective genes) and encompassed various taxa, including uncultured members.

CONCLUSIONS: We outline how this function-centric approach, where all members of a community exhibiting a particular pathofunction are redundant, can contribute to risk assessment and the development of precision treatment directing gut microbiota to increase host health.}, } @article {pmid30265315, year = {2018}, author = {Smith, HJ and Zelaya, AJ and De León, KB and Chakraborty, R and Elias, DA and Hazen, TC and Arkin, AP and Cunningham, AB and Fields, MW}, title = {Impact of hydrologic boundaries on microbial planktonic and biofilm communities in shallow terrestrial subsurface environments.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, pmid = {30265315}, issn = {1574-6941}, abstract = {Subsurface environments contain a large proportion of planetary microbial biomass and harbor diverse communities responsible for mediating biogeochemical cycles important to groundwater used by human society for consumption, irrigation, agriculture and industry. Within the saturated zone, capillary fringe and vadose zones, microorganisms can reside in two distinct phases (planktonic or biofilm), and significant differences in community composition, structure and activity between free-living and attached communities are commonly accepted. However, largely due to sampling constraints and the challenges of working with solid substrata, the contribution of each phase to subsurface processes is largely unresolved. Here, we synthesize current information on the diversity and activity of shallow freshwater subsurface habitats, discuss the challenges associated with sampling planktonic and biofilm communities across spatial, temporal and geological gradients, and discuss how biofilms may be constrained within shallow terrestrial subsurface aquifers. We suggest that merging traditional activity measurements and sequencing/-omics technologies with hydrological parameters important to sediment biofilm assembly and stability will help delineate key system parameters. Ultimately, integration will enhance our understanding of shallow subsurface ecophysiology in terms of bulk-flow through porous media and distinguish the respective activities of sessile microbial communities from more transient planktonic communities to ecosystem service and maintenance.}, } @article {pmid30265314, year = {2018}, author = {Zhao, R and Wang, H and Cheng, X and Yun, Y and Qiu, X}, title = {Upland soil cluster γ dominates the methanotroph communities in the karst Heshang Cave.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy192}, pmid = {30265314}, issn = {1574-6941}, abstract = {Microorganisms are thought to play a critical role in methane (CH4) consumption in karst caves and yet the presence and diversity of methane-oxidizing bacteria (MOB) remain a mystery. In Heshang Cave, CH4 concentration decreases from 1.9 ppm at the entrance to 0.65 ppm inside the cave. To explore the presence and diversity of MOB in this cave, weathered rocks and sediment samples were collected from the cave and subjected to molecular analysis. The abundances of MOB were 107-108 copies g-1 dry sample via quantification of the pmoA gene, which are comparable to or even higher than those reported in other terrestrial environments, and account for up to 20% of the total microbial communities. Phylogenetically, MOB communities were dominated by the 'high-affinity' upland soil cluster γ (USCγ), although the predominance of Type Ia MOB was also detected in the permanently waterlogged stream sediment. The estimated CH4 oxidation potential varied dramatically among samples in the range of 0.6-80 CH4 m-3 d-1. Collectively, this study provides compelling evidence that the high-affinity MOB capable of oxidizing CH4 at the atmospheric level are present in Heshang Cave, which may play an important role in the CH4 consumption, and supports karst caves as important atmospheric CH4 sinks.}, } @article {pmid30265295, year = {2018}, author = {Pereira, J and Lupas, AN}, title = {The Origin of Mitochondria-Specific Outer Membrane β-Barrels from an Ancestral Bacterial Fragment.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2759-2765}, pmid = {30265295}, issn = {1759-6653}, abstract = {Outer membrane β-barrels (OMBBs) are toroidal arrays of antiparallel β-strands that span the outer membrane of Gram-negative bacteria and eukaryotic organelles. Although homologous, most families of bacterial OMBBs evolved through the independent amplification of an ancestral ββ-hairpin. In mitochondria, one family (SAM50) has a clear bacterial ancestry; the origin of the other family, consisting of 19-stranded OMBBs found only in mitochondria (MOMBBs), is substantially unclear. In a large-scale comparison of mitochondrial and bacterial OMBBs, we find evidence that the common ancestor of all MOMBBs emerged by the amplification of a double ββ-hairpin of bacterial origin, probably at the time of the Last Eukaryotic Common Ancestor. Thus, MOMBBs are indeed descended from bacterial OMBBs, but their fold formed independently in the proto-mitochondria, possibly in response to the need for a general-purpose polypeptide importer. This occurred by a process of amplification, despite the final fold having a prime number of strands.}, } @article {pmid30265292, year = {2018}, author = {Pyrihová, E and Motycková, A and Voleman, L and Wandyszewska, N and Fišer, R and Seydlová, G and Roger, A and Kolísko, M and Doležal, P}, title = {A Single Tim Translocase in the Mitosomes of Giardia intestinalis Illustrates Convergence of Protein Import Machines in Anaerobic Eukaryotes.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2813-2822}, pmid = {30265292}, issn = {1759-6653}, support = {MOP-142349//CIHR/Canada ; }, abstract = {Mitochondria have evolved diverse forms across eukaryotic diversity in adaptation to anoxia. Mitosomes are the simplest and the least well-studied type of anaerobic mitochondria. Transport of proteins via TIM complexes, composed of three proteins of the Tim17 protein family (Tim17/22/23), is one of the key unifying aspects of mitochondria and mitochondria-derived organelles. However, multiple experimental and bioinformatic attempts have so far failed to identify the nature of TIM in mitosomes of the anaerobic metamonad protist, Giardia intestinalis, one of the few experimental models for mitosome biology. Here, we present the identification of a single G. intestinalis Tim17 protein (GiTim17), made possible only by the implementation of a metamonad-specific hidden Markov model. While very divergent in primary sequence and in predicted membrane topology, experimental data suggest that GiTim17 is an inner membrane mitosomal protein, forming a disulphide-linked dimer. We suggest that the peculiar GiTim17 sequence reflects adaptation to the unusual, detergent resistant, inner mitosomal membrane. Specific pull-down experiments indicate interaction of GiTim17 with mitosomal Tim44, the tethering component of the import motor complex. Analysis of TIM complexes across eukaryote diversity suggests that a "single Tim" translocase is a convergent adaptation of mitosomes in anaerobic protists, with Tim22 and Tim17 (but not Tim23), providing the protein backbone.}, } @article {pmid30265231, year = {2018}, author = {Gan, L and Zhang, Y and Zhang, L and Li, X and Wang, Z and He, L and Li, Z and Tian, Y}, title = {Planococcus halotolerans sp. nov., isolated from a saline soil sample in China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3500-3505}, doi = {10.1099/ijsem.0.003019}, pmid = {30265231}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Planococcus Bacteria/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; Soil/chemistry ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-positive, coccoid or short rod-shaped, moderate-orange-pigmented, halotolerant and psychrotolerant bacterium, designated strain SCU63T, was isolated from a saline soil sample in China, and characterized by a polyphasic taxonomic approach. 16S rRNA gene sequence similarity of strain SCU63T to species in the genera Planococcus and Planomicrobium ranged from 96.5 to 98.6 %. Phylogenetic trees as well as diagnostic signature nucleotides in the 16S rRNA gene sequence supported the view that this strain should be assigned to the genus Planococcus. Further, average nucleotide identity and digital DNA-DNA hybridization analyses confirmed the separate species status of strain SCU63T relative to the closely related taxa. The isolate grew at 0-40 °C (optimum, 30-35 °C), at pH 6.5-9.0 (pH 7.0-7.5) and in the presence of 0-15 % (w/v) NaCl (3 %). The principal fatty acids were anteiso-C15 : 0, C16 : 1ω7c alcohol, iso-C16 : 0 and iso-C14 : 0, and the dominant isoprenoid quinones were MK-8 and MK-7. The peptidoglycan type was determined to be A4α (l-Lys-d-Glu), and the polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminophospholipid and one unidentified lipid. The DNA G+C content was 44.6 mol%. Based on the genotypic, phenotypic and chemotaxonomic data, strain SCU63T can be classified as a novel species in the genus Planococcus, for which the name Planococcushalotolerans sp. nov. is proposed. The type strain is SCU63T (=CGMCC 1.13628T=KCTC 43001T).}, } @article {pmid30264932, year = {2018}, author = {Lehnert, SJ and Garver, KA and Richard, J and Devlin, RH and Lajoie, C and Pitcher, TE and Heath, DD}, title = {Significant differences in maternal carotenoid provisioning and effects on offspring fitness in Chinook salmon colour morphs.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1876-1893}, doi = {10.1111/jeb.13383}, pmid = {30264932}, issn = {1420-9101}, support = {//Natural Science and Engineering Research Council/ ; }, abstract = {In oviparous species, maternal carotenoid provisioning can deliver diverse fitness benefits to offspring via increased survival, growth and immune function. Despite demonstrated advantages of carotenoids, large intra- and interspecific variation in carotenoid utilization exists, suggesting trade-offs associated with carotenoids. In Chinook salmon (Oncorhynchus tshawytscha), extreme variation in carotenoid utilization delineates two colour morphs (red and white) that differ genetically in their ability to deposit carotenoids into tissues. Here, we take advantage of this natural variation to examine how large differences in maternal carotenoid provisioning influence offspring fitness. Using a full factorial breeding design crossing morphs and common-garden rearing, we measured differences in a suite of fitness-related traits, including survival, growth, viral susceptibility and host response, in offspring of red (carotenoid-rich eggs) and white (carotenoid-poor eggs) females. Eggs of red females had significantly higher carotenoid content than those of white females (6× more); however, this did not translate into measurable differences in offspring fitness. Given that white Chinook salmon may have evolved to counteract their maternal carotenoid deficiency, we also examined the relationship between egg carotenoid content and offspring fitness within each morph separately. Egg carotenoids only had a positive effect within the red morph on survival to eyed-egg (earliest measured trait), but not within the white morph. Although previous work shows that white females benefit from reduced egg predation, our study also supports a hypothesis that white Chinook salmon have evolved additional mechanisms to improve egg survival despite low carotenoids, providing novel insight into evolutionary mechanisms that maintain this stable polymorphism.}, } @article {pmid30264453, year = {2018}, author = {Wackett, LP}, title = {Antibiotic resistance: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3457-3458}, doi = {10.1111/1462-2920.14427}, pmid = {30264453}, issn = {1462-2920}, } @article {pmid30263054, year = {2018}, author = {Romanescu, RG and Espin-Garcia, O and Ma, J and Bull, SB}, title = {Integrating epigenetic, genetic, and phenotypic data to uncover gene-region associations with triglycerides in the GOLDN study.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {57}, pmid = {30263054}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: There has been significant interest in investigating genome-wide and epigenome-wide associations with lipids. Testing at the gene or region level may improve power in such studies.

Methods: We analyze chromosome 11 cytosine-phosphate-guanine (CpG) methylation levels and single-nucleotide polymorphism (SNP) genotypes from the original Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, aiming to explore the association between triglyceride levels and genetic/epigenetic factors. We apply region-based tests of association to methylation and genotype data, in turn, which seek to increase power by reducing the dimension of the gene-region variables. We also investigate whether integrating 2 omics data sets (methylation and genotype) into the triglyceride association analysis helps or hinders detection of candidate gene regions.

Results: Gene-region testing identified 1 CpG region that had been previously reported in the GOLDN study data and another 2 gene regions that are also associated with triglyceride levels. Testing on the combined genetic and epigenetic data detected the same genes as using epigenetic or genetic data alone.

Conclusions: Region-based testing can uncover additional association signals beyond those detected using single-variant testing.}, } @article {pmid30263053, year = {2018}, author = {Deng, X and Wang, B and Fisher, V and Peloso, G and Cupples, A and Liu, CT}, title = {Genome-wide association study for multiple phenotype analysis.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {55}, pmid = {30263053}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Genome-wide association studies often collect multiple phenotypes for complex diseases. Multivariate joint analyses have higher power to detect genetic variants compared with the marginal analysis of each phenotype and are also able to identify loci with pleiotropic effects. We extend the unified score-based association test to incorporate family structure, apply different approaches to analyze multiple traits in GAW20 real samples, and compare the results. Through simulation studies, we confirm that the Type I error rate of the pedigree-based unified score association test is appropriately controlled. In marginalanalysis of triglyceride levels, we found 1 subgenome-wide significant variant on chromosome 6. Joint analyses identified several suggestive genome-wide significant signals, with the pedigree-based unified score association test yielding the greatest number of significant results.}, } @article {pmid30263052, year = {2018}, author = {Zhou, X and Wang, M and Zhang, H and Stewart, WCL and Lin, S}, title = {Logistic Bayesian LASSO for detecting association combining family and case-control data.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {54}, pmid = {30263052}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Because of the limited information from the GAW20 samples when only case-control or trio data are considered, we propose eLBL, an extension of the Logistic Bayesian LASSO (least absolute shrinkage and selection operator) methodology so that both types of data can be analyzed jointly in the hope of obtaining an increased statistical power, especially for detecting association between rare haplotypes and complex diseases. The methodology is further extended to account for familial correlation among the case-control individuals and the trios. A 2-step analysis strategy was taken to first perform a genome-wise single single-nucleotide polymorphism (SNP) search using the Monte Carlo pedigree disequilibrium test (MCPDT) to determine interesting regions for the Adult Treatment Panel (ATP) binary trait. Then eLBL was applied to haplotype blocks covering the flagged SNPs in Step 1. Several significantly associated haplotypes were identified; most are in blocks contained in protein coding genes that appear to be relevant for metabolic syndrome. The results are further substantiated with a Type I error study and by an additional analysis using the triglyceride measurements directly as a quantitative trait.}, } @article {pmid30263051, year = {2018}, author = {Sun, R and Weng, H and Men, R and Xia, X and Chong, KC and Wu, WKK and Zee, BC and Wang, MH}, title = {Gene-methylation epistatic analyses via the W-test identifies enriched signals of neuronal genes in patients undergoing lipid-control treatment.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {53}, pmid = {30263051}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {An increasing number of studies are focused on the epigenetic regulation of DNA to affect gene expression without modifications to the DNA sequence. Methylation plays an important role in shaping disease traits; however, previous studies were mainly experiment, based, resulting in few reports that measured gene-methylation interaction effects via statistical means. In this study, we applied the data set adaptive W-test to measure gene-methylation interactions. Performance was evaluated by the ability to detect a given set of causal markers in the data set obtained from the GAW20. Results from simulation data analyses showed that the W-test was able to detect most markers. The method was also applied to chromosome 11 of the experimental data set and identified clusters of genes with neuronal and retinal functions, including MPPED2I, GUCY2E, NAV2, and ZBTB16. Genes from the TRIM family were also identified; these genes are potentially related to the regulation of triglyceride levels. Our results suggest that the W-test could be an efficient and effective method to detect gene-methylation interactions. Furthermore, the identified genes suggest an interesting relationship between lipid levels and the etiology of neurological disorders.}, } @article {pmid30263050, year = {2018}, author = {Gao, TH and Zhang, J and Miguelangel, DM and Wang, X}, title = {Methods to evaluate rare variants gene-age interaction for triglycerides.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {49}, pmid = {30263050}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Triglycerides are an important measure of heart health. Although more than 90 genes have been found to be associated to lipids, they only explain 12 to 15% of the variance in lipid levels. Evidence suggests that age may interact with the genetic effect on lipid levels. Existing methods to detect the main effect of rare variants cannot be readily applied for testing the gene environment interaction effect of rare variants, as those methods either have unstable results or inflated Type I error rates when the main effect exists. To overcome these difficulties, we developed two statistical methods: testing of optimally weighted combination of single-nucleotide polymorphism (SNP) environment interaction (TOW-SE) and a variable weight TOW-SE (VW-TOW-SE) to test the gene environment interaction effect of rare variants by grouping SNPs into biologically meaningful SNP-sets (SNPs in a gene or pathway) to improve power and interpretability. The proposed methods can be applied to either continuous or binary environmental variables, and to either continuous or binary outcomes. Simulation studies show that Type I error rates of the proposed methods are under control. Comparing the two methods with the existing interaction sequence kernel association test (iSKAT), the VW-TOW-SE is the most powerful test and the TOW-SE is the second most powerful test when gene environment interaction effect exists for both rare and common variants. The three tests were applied to the GAW20 simulated data, among the five regions in which the main effect of common SNPs was simulated and the gene-age interaction effect was not included. As expected, none of the tests indicated positive results.}, } @article {pmid30263049, year = {2018}, author = {Yu, JC and Hsu, FC and Chiu, YF}, title = {Assessment of fenofibrate-methylation interactions on triglycerides using longitudinal family data.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {48}, pmid = {30263049}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; }, abstract = {Background: Triglyceride (TG) concentrations decrease in response to fenofibrate treatment, and also are associated with DNA methylation. But how interactions between fenofibrate response and DNA methylation affect TGs remains unclear.

Methods: In the present study, we identified and compared differential methylation sites associated with TG concentrations in individuals before and after fenofibrate treatment. We then estimated interactions between fenofibrate treatment and methylation to identify differential methylation effects associated with fenofibrate treatment on TG concentrations using the entire longitudinal family sample. To account for within-family and within-individual corrections, the generalized estimating equations approach was used to estimate main and interaction effects between methylation sites and fenofibrate treatment, adjusting for potential confounders. Analyses were also performed with and without adjusting for high-density lipoprotein (HDL) concentrations.

Results: Prior to fenofibrate treatment, 23 cytosine-phosphate-guanine (CpG) sites were significantly associated with TG concentrations, while only 13 CpG sites were identified posttreatment, adjusting for HDL. Without adjusting for HDL, pretreatment, 20 CpG sites were significantly associated with TG concentrations, while only 12 CpG sites were identified posttreatment. Among these sites, only one differential site (cg19003390 in the CPT1A gene) overlapped from pre- and posttreatment measurements regardless of HDL adjustment. Furthermore, 11 methylation sites showed substantial interaction effects (p < 1.43 × 10-7with Bonferroni correction) with or without HDL adjustment when using the whole longitudinal data.

Conclusions: Our analyses suggest that DNA methylation likely modified the effect of fenofibrate on TG concentrations. Differential fenofibrate-associated methylation sites on TGs differed with and without adjusting for HDL concentrations, suggesting that these HDLs and TGs might share some common epigenetic processes.}, } @article {pmid30263048, year = {2018}, author = {Yang, HC and Chen, CW}, title = {Homozygosity disequilibrium associated with treatment response and its methylation regulation.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {45}, pmid = {30263048}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Homozygosity disequilibrium (HD), indicating a nonrandom pattern of sizable runs of homozygosity that deviates from a random allocation of homozygous and heterozygous genotypes in the genome, is an important phenomenon in population genomics and medical genomics. We performed the first genome-wide study investigating the roles of HD in pharmacogenomics and pharmacoepigenomics by analyzing GAW20 data. We inferred whole-genome profiles of homozygosity intensities and performed genome-wide homozygosity association analyses to identify regions of HD associated with triglyceride (TG) response to fenofibrate by using LOHAS (Loss-of-Heterozygosity Analysis Suite) software. The analysis identified a region of HD contained in MACROD2 at 20p12 to be significantly associated with TG response to fenofibrate. We also examined the common genetic component in TG and methylation responses to fenofibrate. The methylation response to fenofibrate was regarded as a methylation quantitative trait, and our methylation quantitative trait locus analysis identified a cis-acting regulation association with marginal significance between the homozygosity intensity of MACROD2 and the methylation response to fenofibrate. These findings may help delineate the genetic basis of pharmacogenomic and pharmacoepigenomic responses to fenofibrate intervention.}, } @article {pmid30263047, year = {2018}, author = {Hsu, Y and Auerbach, J and Zheng, T and Lo, SH}, title = {Coping with family structure in genome-wide association studies: a comparative evaluation.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {42}, pmid = {30263047}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {In this paper, a fully statistical investigation of the control of family structure as random effects is analyzed and discussed, using both the genome-wide association studies (GWAS) data and simulated data. Three modeling strategies are proposed and the analysis results suggest the hybrid use of results from all possible models should be combined in practice.}, } @article {pmid30263046, year = {2018}, author = {Daw, EW and Hicks, J and Lenzini, P and Lin, SJ and Wang, J and Williams, C and An, P and Province, MA and Kraja, AT}, title = {Methods for detecting methylation by SNP interaction in GAW20 simulation.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {37}, pmid = {30263046}, issn = {1753-6561}, support = {R01 HL104135/HL/NHLBI NIH HHS/United States ; R01 HL091357/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; U01 AG023746/AG/NIA NIH HHS/United States ; R01 HL117078/HL/NHLBI NIH HHS/United States ; }, abstract = {To examine whether single-nucleotide polymorphism (SNP) by methylation interactions can be detected, we analyzed GAW20 simulated triglycerides at visits 3 and 4 against baseline (visits 1 and 2) under 4 general linear models and 2 tree-based models in 200 replications of a sample of 680 individuals. Effects for SNPs, methylation cytosine-phosphate-guanine (CpG) effects, and interactions for SNP/CpG pairs were included. Causative SNPs/CpG pairs distributed on autosomal chromosomes 1 to 20 were tested to examine sensitivity. We also tested noncausative SNP/CpG pairs on chromosomes 21 and 22 to estimate the empirical null. We found reasonable power to detect the main causative loci, with the exact power depending on sample size and strength of effects at the SNP and CpG sites.}, } @article {pmid30263045, year = {2018}, author = {Blackburn, NB and Porto, A and Peralta, JM and Blangero, J}, title = {Heritability and genetic associations of triglyceride and HDL-C levels using pedigree-based and empirical kinships.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {34}, pmid = {30263045}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {The heritability of a phenotype is an estimation of the percent of variance in that phenotype that is attributable to additive genetic factors. Heritability is optimally estimated in family-based sample populations. Traditionally, this involves use of a pedigree-based kinship coefficient generated from the collected genealogical relationships between family members. An alternative, when dense genotype data are available, is to directly measure the empirical kinship between samples. This study compares the use of pedigree and empirical kinships in the GAW20 data set. Two phenotypes were assessed: triglyceride levels and high-density lipoprotein cholesterol (HDL-C) levels pre- and postintervention with the cholesterol-reducing drug fenofibrate. Using SOLAR (Sequential Oligogenic Linkage Analysis Routines), pedigree-based kinships and empirically calculated kinships (using IBDLD and LDAK) were used to calculate phenotype heritability. In addition, a genome-wide association study was conducted using each kinship model for each phenotype to identify genetic variants significantly associated with phenotypic variation. The variant rs247617 was significantly associated with HDL-C levels both pre- and post-fenofibrate intervention. Overall, the phenotype heritabilities calculated using pedigree based kinships or either of the empirical kinships generated using IBDLD or LDAK were comparable. Phenotype heritabilities estimated from empirical kinships generated using IBDLD were closest to the pedigree-based estimations. Given that there was not an appreciable amount of unknown relatedness between the pedigrees in this data set, a large increase in heritability in using empirical kinship was not expected, and our calculations support this. Importantly, these results demonstrate that when sufficient genotypic data are available, empirical kinship estimation is a practical alternative to using pedigree-based kinships.}, } @article {pmid30263044, year = {2018}, author = {Zhao, K and Jiang, L and Klein, K and Greenwood, CMT and Oualkacha, K}, title = {CpG-set association assessment of lipid concentration changes and DNA methylation.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {30}, pmid = {30263044}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Epigenome association studies that test a large number of methylation sites suffer from stringent multiple-testing corrections. This study's goals were to investigate region-based associations between DNA methylation sites and lipid-level changes in response to the treatment with fenofibrate in the GAW20 data and to investigate whether improvements in power could be obtained by taking into account correlations between DNA methylation at neighboring cytosine-phosphate-guanine (CpG) sites. To this end, we applied both a recently developed block-based data-dimension-reduction approach and a region-based variance-component (VC) linear mixed model to GAW20 data. We compared analyses of unrelated individuals with familial data. The region-based VC approach using unrelated (independent) individuals identified the gene LGALS9C as significantly associated with changes in triglycerides. However, univariate tests of individual CpG sites yielded no valid statistically significant results.}, } @article {pmid30263043, year = {2018}, author = {Almeida, M and Peralta, J and Garcia, J and Diego, V and Goring, H and Williams-Blangero, S and Blangero, J}, title = {Modeling methylation data as an additional genetic variance component.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {29}, pmid = {30263043}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {High-throughput platforms allow the characterization of thousands of previously known methylation sites. These platforms have great potential for investigating the epigenetic effects that are partially responsible for gene expression control. Methylation sites provide a bridge for the investigation of real-time environmental contributions on genomic events by the alteration of methylation status of those sites. Using the data provided by GAW20's organization committee, we calculated the heritability estimates of each cytosine-phosphate-guanine (CpG) island before and after the use of fenofibrate, a lipid-control drug. Surprisingly, we detected substantially high heritability estimates before drug usage. This somewhat unexpected high sample correlation was corrected by the use of principal components and the distributions of heritability estimates before and after fenofibrate treatment, which made the distributions comparable. The methylation sites located near a gene were collected and a genetic relationship matrix estimated to represent the overall correlation between samples. We implemented a random-effect association test to screen genes whose methylation patterns partially explain the observable high-density lipoprotein (HDL) heritability. Our leading association was observed for the TMEM52 gene that encodes a transmembrane protein, and is largely expressed in the liver, had not been previously associated with HDL until this manuscript. Using a variance component decomposition framework with the linear mixed model allows the integration of data from different sources, such as methylation, gene expression, metabolomics, and proteomics. The decomposition of the genetic variance component decomposition provides a flexible analytical approach for the challenges of this new omics era.}, } @article {pmid30263042, year = {2018}, author = {Tintle, NL and Fardo, DW and de Andrade, M and Aslibekyan, S and Bailey, JN and Bermejo, JL and Cantor, RM and Ghosh, S and Melton, P and Wang, X and MacCluer, JW and Almasy, L}, title = {GAW20: methods and strategies for the new frontiers of epigenetics and pharmacogenomics.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {26}, doi = {10.1186/s12919-018-0113-1}, pmid = {30263042}, issn = {1753-6561}, support = {R01 HL104135/HL/NHLBI NIH HHS/United States ; R15 HG006915/HG/NHGRI NIH HHS/United States ; K01 HL136700/HL/NHLBI NIH HHS/United States ; R01 HL091357/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {GAW20 provided a platform for developing and evaluating statistical methods to analyze human lipid-related phenotypes, DNA methylation, and single-nucleotide markers in a study involving a pharmaceutical intervention. In this article, we present an overview of the data sets and the contributions analyzing these data. The data, donated by the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) investigators, included data from 188 families (N = 1105) which included genome-wide DNA methylation data before and after a 3-week treatment with fenofibrate, single-nucleotide polymorphisms, metabolic syndrome components before and after treatment, and a variety of covariates. The contributions from individual research groups were extensively discussed prior, during, and after the Workshop in groups based on discussion themes, before being submitted for publication.}, } @article {pmid30263041, year = {2018}, author = {Datta, S and Fang, Y and Loh, JM}, title = {Joint screening of ultrahigh dimensional variables for family-based genetic studies.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {24}, pmid = {30263041}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: Mixed models are a useful tool for evaluating the association between an outcome variable and genetic variables from a family-based genetic study, taking into account the kinship coefficients. When there are ultrahigh dimensional genetic variables (ie, p ≫ n), it is challenging to fit any mixed effect model.

Methods: We propose a two-stage strategy, screening genetic variables in the first stage and then fitting the mixed effect model in the second stage to those variables that survive the screening. For the screening stage, we can use the sure independence screening (SIS) procedure, which fits the mixed effect model to one genetic variable at a time. Because the SIS procedure may fail to identify those marginally unimportant but jointly important genetic variables, we propose a joint screening (JS) procedure that screens all the genetic variables simultaneously. We evaluate the performance of the proposed JS procedure via a simulation study and an application to the GAW20 data.

Results: We perform the proposed JS procedure on the GAW20 representative simulated data set (n = 680 participant(s) and p = 463,995 CpG cytosine-phosphate-guanine [CpG] sites) and select the top d = ⌊n/ log(n)⌋ variables. Then we fit the mixed model using these top variables. Under significance level, 5%, 43 CpG sites are found to be significant. Some diagnostic analyses based on the residuals show the fitted mixed model is appropriate.

Conclusions: Although the GAW20 data set is ultrahigh dimensional and family-based having within group variances, we were successful in performing subset selection using a two-step strategy that is computationally simple and easy to understand.}, } @article {pmid30263040, year = {2018}, author = {Islam, MM and Tian, Y and Cheng, Y and Wang, Y and Hu, P}, title = {A deep neural network based regression model for triglyceride concentrations prediction using epigenome-wide DNA methylation profiles.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 9}, pages = {21}, pmid = {30263040}, issn = {1753-6561}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {Background: Epigenetic modification has an effect on gene expression under the environmental alteration, but it does not change corresponding genome sequence. DNA methylation (DNAm) is one of the important epigenetic mechanisms. DNAm variations could be used as epigenetic markers to predict and account for the change of many human phenotypic traits, such as cancer, diabetes, and high blood pressure. In this study, we built deep neural network (DNN) regression models to account for interindividual variation in triglyceride concentrations measured at different visits of peripheral blood samples using epigenome-wide DNAm profiles.

Results: We used epigenome-wide DNAm profiles of before and after medication interventions (called pretreatment and posttreatment, respectively) to predict triglyceride concentrations for peripheral blood draws at visit 2 (using pretreatment data) and at visit 4 (using both pretreatment and posttreatment data). Our experimental results showed that DNN models can predict triglyceride concentrations for blood draws at visit 4 using pretreatment and posttreatment DNAm data more accurately than for blood draws at visit 2 using pretreatment DNAm data. Furthermore, we got the best prediction results when we used pretreatment DNAm data to predict triglyceride concentrations for blood draws at visit 4, which suggests a long-term epigenetic effect on phenotypic traits. We compared the prediction performances of our proposed DNN models with that of support vector machine (SVM). This comparison showed that our DNN models achieved better prediction performance than did SVM.

Conclusions: We demonstrated the superiority of our proposed DNN models over the SVM model for predicting triglyceride concentrations. This study also suggests that the DNN approach has advantages over other traditional machine-learning methods to model high-dimensional epigenome-wide DNAm data and other genomic data.}, } @article {pmid30262844, year = {2018}, author = {York, A}, title = {Surf's up!.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {658-659}, doi = {10.1038/s41579-018-0093-1}, pmid = {30262844}, issn = {1740-1534}, } @article {pmid30262818, year = {2018}, author = {Lee, JK and Liu, Z and Sa, JK and Shin, S and Wang, J and Bordyuh, M and Cho, HJ and Elliott, O and Chu, T and Choi, SW and Rosenbloom, DIS and Lee, IH and Shin, YJ and Kang, HJ and Kim, D and Kim, SY and Sim, MH and Kim, J and Lee, T and Seo, YJ and Shin, H and Lee, M and Kim, SH and Kwon, YJ and Oh, JW and Song, M and Kim, M and Kong, DS and Choi, JW and Seol, HJ and Lee, JI and Kim, ST and Park, JO and Kim, KM and Song, SY and Lee, JW and Kim, HC and Lee, JE and Choi, MG and Seo, SW and Shim, YM and Zo, JI and Jeong, BC and Yoon, Y and Ryu, GH and Kim, NKD and Bae, JS and Park, WY and Lee, J and Verhaak, RGW and Iavarone, A and Lee, J and Rabadan, R and Nam, DH}, title = {Pharmacogenomic landscape of patient-derived tumor cells informs precision oncology therapy.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1399-1411}, doi = {10.1038/s41588-018-0209-6}, pmid = {30262818}, issn = {1546-1718}, abstract = {Outcomes of anticancer therapy vary dramatically among patients due to diverse genetic and molecular backgrounds, highlighting extensive intertumoral heterogeneity. The fundamental tenet of precision oncology defines molecular characterization of tumors to guide optimal patient-tailored therapy. Towards this goal, we have established a compilation of pharmacological landscapes of 462 patient-derived tumor cells (PDCs) across 14 cancer types, together with genomic and transcriptomic profiling in 385 of these tumors. Compared with the traditional long-term cultured cancer cell line models, PDCs recapitulate the molecular properties and biology of the diseases more precisely. Here, we provide insights into dynamic pharmacogenomic associations, including molecular determinants that elicit therapeutic resistance to EGFR inhibitors, and the potential repurposing of ibrutinib (currently used in hematological malignancies) for EGFR-specific therapy in gliomas. Lastly, we present a potential implementation of PDC-derived drug sensitivities for the prediction of clinical response to targeted therapeutics using retrospective clinical studies.}, } @article {pmid30262817, year = {2018}, author = {McDermott, U}, title = {Cancer cell lines as patient avatars for drug response prediction.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1350-1351}, doi = {10.1038/s41588-018-0245-2}, pmid = {30262817}, issn = {1546-1718}, } @article {pmid30262816, year = {2018}, author = {Kragesteen, BK and Spielmann, M and Paliou, C and Heinrich, V and Schöpflin, R and Esposito, A and Annunziatella, C and Bianco, S and Chiariello, AM and Jerković, I and Harabula, I and Guckelberger, P and Pechstein, M and Wittler, L and Chan, WL and Franke, M and Lupiáñez, DG and Kraft, K and Timmermann, B and Vingron, M and Visel, A and Nicodemi, M and Mundlos, S and Andrey, G}, title = {Dynamic 3D chromatin architecture contributes to enhancer specificity and limb morphogenesis.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1463-1473}, doi = {10.1038/s41588-018-0221-x}, pmid = {30262816}, issn = {1546-1718}, abstract = {The regulatory specificity of enhancers and their interaction with gene promoters is thought to be controlled by their sequence and the binding of transcription factors. By studying Pitx1, a regulator of hindlimb development, we show that dynamic changes in chromatin conformation can restrict the activity of enhancers. Inconsistent with its hindlimb-restricted expression, Pitx1 is controlled by an enhancer (Pen) that shows activity in forelimbs and hindlimbs. By Capture Hi-C and three-dimensional modeling of the locus, we demonstrate that forelimbs and hindlimbs have fundamentally different chromatin configurations, whereby Pen and Pitx1 interact in hindlimbs and are physically separated in forelimbs. Structural variants can convert the inactive into the active conformation, thereby inducing Pitx1 misexpression in forelimbs, causing partial arm-to-leg transformation in mice and humans. Thus, tissue-specific three-dimensional chromatin conformation can contribute to enhancer activity and specificity in vivo and its disturbance can result in gene misexpression and disease.}, } @article {pmid30262815, year = {2018}, author = {Marti-Renom, MA and Almouzni, G and Bickmore, WA and Bystricky, K and Cavalli, G and Fraser, P and Gasser, SM and Giorgetti, L and Heard, E and Nicodemi, M and Nollmann, M and Orozco, M and Pombo, A and Torres-Padilla, ME}, title = {Challenges and guidelines toward 4D nucleome data and model standards.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1352-1358}, doi = {10.1038/s41588-018-0236-3}, pmid = {30262815}, issn = {1546-1718}, support = {MC_PC_U127527202//Medical Research Council/United Kingdom ; }, abstract = {Due to recent advances in experimental and theoretical approaches, the dynamic three-dimensional organization (3D) of the nucleus has become a very active area of research in life sciences. We now understand that the linear genome is folded in ways that may modulate how genes are expressed during the basic functioning of cells. Importantly, it is now possible to build 3D models of how the genome folds within the nucleus and changes over time (4D). Because genome folding influences its function, this opens exciting new possibilities to broaden our understanding of the mechanisms that determine cell fate. However, the rapid evolution of methods and the increasing complexity of data can result in ambiguity and reproducibility challenges, which may hamper the progress of this field. Here, we describe such challenges ahead and provide guidelines to think about strategies for shared standardized validation of experimental 4D nucleome data sets and models.}, } @article {pmid30262814, year = {2018}, author = {}, title = {The measure of a healthy society.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1345}, doi = {10.1038/s41588-018-0249-y}, pmid = {30262814}, issn = {1546-1718}, } @article {pmid30262654, year = {2018}, author = {Rosch, RE and Wright, S and Cooray, G and Papadopoulou, M and Goyal, S and Lim, M and Vincent, A and Upton, AL and Baldeweg, T and Friston, KJ}, title = {NMDA-receptor antibodies alter cortical microcircuit dynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9916-E9925}, pmid = {30262654}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 106556/Z/14/Z//Wellcome Trust/United Kingdom ; 088130/Z/09/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Antibodies/*adverse effects ; Brain/*drug effects/immunology/metabolism ; Cerebral Cortex/*drug effects/immunology/metabolism ; Cortical Synchronization/*drug effects ; Encephalitis/*etiology/metabolism/pathology ; Excitatory Postsynaptic Potentials ; Humans ; Mice ; Receptors, N-Methyl-D-Aspartate/*immunology ; }, abstract = {NMDA-receptor antibodies (NMDAR-Abs) cause an autoimmune encephalitis with a diverse range of EEG abnormalities. NMDAR-Abs are believed to disrupt receptor function, but how blocking this excitatory synaptic receptor can lead to paroxysmal EEG abnormalities-or even seizures-is poorly understood. Here we show that NMDAR-Abs change intrinsic cortical connections and neuronal population dynamics to alter the spectral composition of spontaneous EEG activity and predispose brain dynamics to paroxysmal abnormalities. Based on local field potential recordings in a mouse model, we first validate a dynamic causal model of NMDAR-Ab effects on cortical microcircuitry. Using this model, we then identify the key synaptic parameters that best explain EEG paroxysms in pediatric patients with NMDAR-Ab encephalitis. Finally, we use the mouse model to show that NMDAR-Ab-related changes render microcircuitry critically susceptible to overt EEG paroxysms when these key parameters are changed, even though the same parameter fluctuations are tolerated in the in silico model of the control condition. These findings offer mechanistic insights into circuit-level dysfunction induced by NMDAR-Ab.}, } @article {pmid30262653, year = {2018}, author = {Micoli, F and Rondini, S and Alfini, R and Lanzilao, L and Necchi, F and Negrea, A and Rossi, O and Brandt, C and Clare, S and Mastroeni, P and Rappuoli, R and Saul, A and MacLennan, CA}, title = {Comparative immunogenicity and efficacy of equivalent outer membrane vesicle and glycoconjugate vaccines against nontyphoidal Salmonella.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10428-10433}, pmid = {30262653}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 206194//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Antibodies, Bacterial/blood/*immunology ; Glycoconjugates/*immunology ; Mice ; O Antigens/*immunology ; Salmonella Infections/*immunology/prevention & control ; Salmonella Vaccines/*therapeutic use ; Salmonella enteritidis/*immunology ; Salmonella typhimurium/*immunology ; Vaccination ; }, abstract = {Nontyphoidal Salmonellae cause a devastating burden of invasive disease in sub-Saharan Africa with high levels of antimicrobial resistance. Vaccination has potential for a major global health impact, but no licensed vaccine is available. The lack of commercial incentive makes simple, affordable technologies the preferred route for vaccine development. Here we compare equivalent Generalized Modules for Membrane Antigens (GMMA) outer membrane vesicles and O-antigen-CRM197 glycoconjugates to deliver lipopolysaccharide O-antigen in bivalent Salmonella Typhimurium and Enteritidis vaccines. Salmonella strains were chosen and tolR deleted to induce GMMA production. O-antigens were extracted from wild-type bacteria and conjugated to CRM197 Purified GMMA and glycoconjugates were characterized and tested in mice for immunogenicity and ability to reduce Salmonella infection. GMMA and glycoconjugate O-antigen had similar structural characteristics, O-acetylation, and glucosylation levels. Immunization with GMMA induced higher anti-O-antigen IgG than glycoconjugate administered without Alhydrogel adjuvant. With Alhydrogel, antibody levels were similar. GMMA induced a diverse antibody isotype profile with greater serum bactericidal activity than glycoconjugate, which induced almost exclusively IgG1. Immunization reduced bacterial colonization of mice subsequently infected with SalmonellaS Typhimurium numbers were lower in tissues of mice vaccinated with GMMA compared with glycoconjugate. S. Enteritidis burden in the tissues was similar in mice immunized with either vaccine. With favorable immunogenicity, low cost, and ability to induce functional antibodies and reduce bacterial burden, GMMA offer a promising strategy for the development of a nontyphoidal Salmonella vaccine compared with established glycoconjugates. GMMA technology is potentially attractive for development of vaccines against other bacteria of global health significance.}, } @article {pmid30262652, year = {2018}, author = {Horn, Z and Behesti, H and Hatten, ME}, title = {N-cadherin provides a cis and trans ligand for astrotactin that functions in glial-guided neuronal migration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10556-10563}, pmid = {30262652}, issn = {1091-6490}, mesh = {Animals ; Cadherins/*physiology ; *Cell Adhesion ; *Cell Movement ; Cells, Cultured ; Cerebellum/cytology/*physiology ; Glycoproteins/genetics/*metabolism ; Ligands ; Nerve Tissue Proteins/genetics/*metabolism ; Neurogenesis ; Neuroglia/cytology/*physiology ; Neurons/cytology/*physiology ; }, abstract = {Prior studies demonstrate that astrotactin (ASTN1) provides a neuronal receptor for glial-guided CNS migration. Here we report that ASTN1 binds N-cadherin (CDH2) and that the ASTN1:CDH2 interaction supports cell-cell adhesion. To test the function of ASTN1:CDH2 binding in glial-guided neuronal migration, we generated a conditional loss of Cdh2 in cerebellar granule cells and in glia. Granule cell migration was slowed in cerebellar slice cultures after a conditional loss of neuronal Cdh2, and more severe migration defects occurred after a conditional loss of glial Cdh2 Expression in granule cells of a mutant form of ASTN1 that does not bind CDH2 also slowed migration. Moreover, in vitro chimeras of granule cells and glia showed impaired neuron-glia attachment in the absence of glial, but not neuronal, Cdh2 Thus, cis and trans bindings of ASTN1 to neuronal and glial CDH2 form an asymmetric neuron-glial bridge complex that promotes glial-guided neuronal migration.}, } @article {pmid30262651, year = {2018}, author = {van Kerkoerle, T and Marik, SA and Meyer Zum Alten Borgloh, S and Gilbert, CD}, title = {Axonal plasticity associated with perceptual learning in adult macaque primary visual cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10464-10469}, pmid = {30262651}, issn = {1091-6490}, support = {R01 EY007968/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Axons/*physiology ; Learning/*physiology ; Macaca ; Neuronal Plasticity/*physiology ; Visual Cortex/*physiology ; Visual Perception/*physiology ; }, abstract = {Perceptual learning is associated with changes in the functional properties of neurons even in primary sensory areas. In macaque monkeys trained to perform a contour detection task, we have observed changes in contour-related facilitation of neuronal responses in primary visual cortex that track their improvement in performance on a contour detection task. We have previously explored the anatomical substrate of experience-dependent changes in the visual cortex based on a retinal lesion model, where we find sprouting and pruning of the axon collaterals in the cortical lesion projection zone. Here, we attempted to determine whether similar changes occur under normal visual experience, such as that associated with perceptual learning. We labeled the long-range horizontal connections in visual cortex by virally mediated transfer of genes expressing fluorescent probes, which enabled us to do longitudinal two-photon imaging of axonal arbors over the period during which animals improve in contour detection performance. We found that there are substantial changes in the axonal arbors of neurons in cortical regions representing the trained part of the visual field, with sprouting of new axon collaterals and pruning of preexisting axon collaterals. Our findings indicate that changes in the structure of axonal arbors are part of the circuit-level mechanism of perceptual learning, and further support the idea that the learned information is encoded at least in part in primary visual cortex.}, } @article {pmid30262650, year = {2018}, author = {Rohrback, S and April, C and Kaper, F and Rivera, RR and Liu, CS and Siddoway, B and Chun, J}, title = {Submegabase copy number variations arise during cerebral cortical neurogenesis as revealed by single-cell whole-genome sequencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10804-10809}, pmid = {30262650}, issn = {1091-6490}, support = {R01 AA021402/AA/NIAAA NIH HHS/United States ; T32 GM007752/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cerebral Cortex/*cytology/*metabolism ; *DNA Copy Number Variations ; Embryo, Mammalian/cytology/metabolism ; *Gene Expression Regulation, Developmental ; Genome ; Genomics ; Mice ; Mice, Inbred C57BL ; Neurogenesis/*genetics ; Single-Cell Analysis/*methods ; Whole Genome Sequencing/*methods ; }, abstract = {Somatic copy number variations (CNVs) exist in the brain, but their genesis, prevalence, forms, and biological impact remain unclear, even within experimentally tractable animal models. We combined a transposase-based amplification (TbA) methodology for single-cell whole-genome sequencing with a bioinformatic approach for filtering unreliable CNVs (FUnC), developed from machine learning trained on lymphocyte V(D)J recombination. TbA-FUnC offered superior genomic coverage and removed >90% of false-positive CNV calls, allowing extensive examination of submegabase CNVs from over 500 cells throughout the neurogenic period of cerebral cortical development in Mus musculus Thousands of previously undocumented CNVs were identified. Half were less than 1 Mb in size, with deletions 4× more common than amplification events, and were randomly distributed throughout the genome. However, CNV prevalence during embryonic cortical development was nonrandom, peaking at midneurogenesis with levels triple those found at younger ages before falling to intermediate quantities. These data identify pervasive small and large CNVs as early contributors to neural genomic mosaicism, producing genomically diverse cellular building blocks that form the highly organized, mature brain.}, } @article {pmid30262649, year = {2018}, author = {Hong, S and Sunita, S and Maehigashi, T and Hoffer, ED and Dunkle, JA and Dunham, CM}, title = {Mechanism of tRNA-mediated +1 ribosomal frameshifting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11226-11231}, pmid = {30262649}, issn = {1091-6490}, support = {P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 GM093278/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; }, mesh = {Bacteria/genetics ; Codon/genetics ; Frameshift Mutation/*genetics ; Frameshifting, Ribosomal/*genetics ; Peptide Elongation Factor G/genetics ; Protein Biosynthesis/genetics ; RNA, Messenger/genetics ; RNA, Ribosomal, 16S/genetics ; RNA, Transfer/*genetics ; Reading Frames/genetics ; Ribosomes/*genetics ; }, abstract = {Accurate translation of the genetic code is critical to ensure expression of proteins with correct amino acid sequences. Certain tRNAs can cause a shift out of frame (i.e., frameshifting) due to imbalances in tRNA concentrations, lack of tRNA modifications or insertions or deletions in tRNAs (called frameshift suppressors). Here, we determined the structural basis for how frameshift-suppressor tRNASufA6 (a derivative of tRNAPro) reprograms the mRNA frame to translate a 4-nt codon when bound to the bacterial ribosome. After decoding at the aminoacyl (A) site, the crystal structure of the anticodon stem-loop of tRNASufA6 bound in the peptidyl (P) site reveals ASL conformational changes that allow for recoding into the +1 mRNA frame. Furthermore, a crystal structure of full-length tRNASufA6 programmed in the P site shows extensive conformational rearrangements of the 30S head and body domains similar to what is observed in a translocation intermediate state containing elongation factor G (EF-G). The 30S movement positions tRNASufA6 toward the 30S exit (E) site disrupting key 16S rRNA-mRNA interactions that typically define the mRNA frame. In summary, this tRNA-induced 30S domain change in the absence of EF-G causes the ribosome to lose its grip on the mRNA and uncouples the canonical forward movement of the tRNAs during elongation.}, } @article {pmid30262635, year = {2018}, author = {Murakami, H and Levin, E and Delworth, TL and Gudgel, R and Hsu, PC}, title = {Dominant effect of relative tropical Atlantic warming on major hurricane occurrence.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6416}, pages = {794-799}, doi = {10.1126/science.aat6711}, pmid = {30262635}, issn = {1095-9203}, abstract = {Here we explore factors potentially linked to the enhanced major hurricane activity in the Atlantic Ocean during 2017. Using a suite of high-resolution model experiments, we show that the increase in 2017 major hurricanes was not primarily caused by La Niña conditions in the Pacific Ocean but rather triggered mainly by pronounced warm sea surface conditions in the tropical North Atlantic. Further, we superimpose a similar pattern of North Atlantic surface warming on data for long-term increasing sea surface temperature (a product of increases in greenhouse gas concentrations and decreases in aerosols) to show that this warming trend will likely lead to even higher numbers of major hurricanes in the future. The key factor controlling Atlantic major hurricane activity appears to be the degree to which the tropical Atlantic warms relative to the rest of the global ocean.}, } @article {pmid30262634, year = {2018}, author = {Gerber, T and Murawala, P and Knapp, D and Masselink, W and Schuez, M and Hermann, S and Gac-Santel, M and Nowoshilow, S and Kageyama, J and Khattak, S and Currie, JD and Camp, JG and Tanaka, EM and Treutlein, B}, title = {Single-cell analysis uncovers convergence of cell identities during axolotl limb regeneration.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aaq0681}, pmid = {30262634}, issn = {1095-9203}, mesh = {Ambystoma mexicanum ; Animals ; Cell Lineage ; Cell Tracking ; Cellular Reprogramming/*physiology ; Connective Tissue Cells/*physiology ; Forelimb/*physiology ; Genes, Reporter ; Integrases ; RNA, Messenger/genetics ; Regeneration/*physiology ; Sequence Analysis, RNA/methods ; Single-Cell Analysis ; Stem Cells/physiology ; }, abstract = {Amputation of the axolotl forelimb results in the formation of a blastema, a transient tissue where progenitor cells accumulate prior to limb regeneration. However, the molecular understanding of blastema formation had previously been hampered by the inability to identify and isolate blastema precursor cells in the adult tissue. We have used a combination of Cre-loxP reporter lineage tracking and single-cell messenger RNA sequencing (scRNA-seq) to molecularly track mature connective tissue (CT) cell heterogeneity and its transition to a limb blastema state. We have uncovered a multiphasic molecular program where CT cell types found in the uninjured adult limb revert to a relatively homogenous progenitor state that recapitulates an embryonic limb bud-like phenotype including multipotency within the CT lineage. Together, our data illuminate molecular and cellular reprogramming during complex organ regeneration in a vertebrate.}, } @article {pmid30262633, year = {2018}, author = {Lan, P and Tan, M and Zhang, Y and Niu, S and Chen, J and Shi, S and Qiu, S and Wang, X and Peng, X and Cai, G and Cheng, H and Wu, J and Li, G and Lei, M}, title = {Structural insight into precursor tRNA processing by yeast ribonuclease P.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {}, doi = {10.1126/science.aat6678}, pmid = {30262633}, issn = {1095-9203}, abstract = {Ribonuclease P (RNase P) is a universal ribozyme responsible for processing the 5'-leader of pre-transfer RNA (pre-tRNA). Here, we report the 3.5-angstrom cryo-electron microscopy structures of Saccharomyces cerevisiae RNase P alone and in complex with pre-tRNAPhe The protein components form a hook-shaped architecture that wraps around the RNA and stabilizes RNase P into a "measuring device" with two fixed anchors that recognize the L-shaped pre-tRNA. A universally conserved uridine nucleobase and phosphate backbone in the catalytic center together with the scissile phosphate and the O3' leaving group of pre-tRNA jointly coordinate two catalytic magnesium ions. Binding of pre-tRNA induces a conformational change in the catalytic center that is required for catalysis. Moreover, simulation analysis suggests a two-metal-ion SN2 reaction pathway of pre-tRNA cleavage. These results not only reveal the architecture of yeast RNase P but also provide a molecular basis of how the 5'-leader of pre-tRNA is processed by eukaryotic RNase P.}, } @article {pmid30262632, year = {2018}, author = {Mandal, J and Fu, Y and Overvig, AC and Jia, M and Sun, K and Shi, NN and Zhou, H and Xiao, X and Yu, N and Yang, Y}, title = {Hierarchically porous polymer coatings for highly efficient passive daytime radiative cooling.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {315-319}, doi = {10.1126/science.aat9513}, pmid = {30262632}, issn = {1095-9203}, abstract = {Passive daytime radiative cooling (PDRC) involves spontaneously cooling a surface by reflecting sunlight and radiating heat to the cold outer space. Current PDRC designs are promising alternatives to electrical cooling but are either inefficient or have limited applicability. We present a simple, inexpensive, and scalable phase inversion-based method for fabricating hierarchically porous poly(vinylidene fluoride-co-hexafluoropropene) [P(VdF-HFP)HP] coatings with excellent PDRC capability. High, substrate-independent hemispherical solar reflectances (0.96 ± 0.03) and long-wave infrared emittances (0.97 ± 0.02) allow for subambient temperature drops of ~6°C and cooling powers of ~96 watts per square meter (W m-2) under solar intensities of 890 and 750 W m-2, respectively. The performance equals or surpasses those of state-of-the-art PDRC designs, and the technique offers a paint-like simplicity.}, } @article {pmid30262504, year = {2018}, author = {Furnell, K}, title = {Breaking the silence.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1410}, doi = {10.1126/science.361.6409.1410}, pmid = {30262504}, issn = {1095-9203}, mesh = {*Disclosure ; Education, Graduate ; Female ; Humans ; *Mental Health ; Mentors/psychology ; Personality Disorders/*psychology ; *Social Stigma ; Students/*psychology ; }, } @article {pmid30262503, year = {2018}, author = {He, S and Del Viso, F and Chen, CY and Ikmi, A and Kroesen, AE and Gibson, MC}, title = {An axial Hox code controls tissue segmentation and body patterning in Nematostella vectensis.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1377-1380}, doi = {10.1126/science.aar8384}, pmid = {30262503}, issn = {1095-9203}, mesh = {Animals ; Bacterial Proteins ; Body Patterning/*genetics ; CRISPR-Associated Protein 9 ; CRISPR-Cas Systems ; Endoderm/cytology/growth & development ; Endonucleases ; *Gene Expression Regulation, Developmental ; Gene Knockdown Techniques/methods ; Genes, Homeobox/genetics/*physiology ; Larva/cytology/genetics/growth & development ; Mutagenesis ; RNA, Small Interfering/genetics ; Sea Anemones/cytology/genetics/*growth & development ; Transcription Factors/genetics/*physiology ; }, abstract = {Hox genes encode conserved developmental transcription factors that govern anterior-posterior (A-P) pattering in diverse bilaterian animals, which display bilateral symmetry. Although Hox genes are also present within Cnidaria, these simple animals lack a definitive A-P axis, leaving it unclear how and when a functionally integrated Hox code arose during evolution. We used short hairpin RNA (shRNA)-mediated knockdown and CRISPR-Cas9 mutagenesis to demonstrate that a Hox-Gbx network controls radial segmentation of the larval endoderm during development of the sea anemone Nematostella vectensis. Loss of Hox-Gbx activity also elicits marked defects in tentacle patterning along the directive (orthogonal) axis of primary polyps. On the basis of our results, we propose that an axial Hox code may have controlled body patterning and tissue segmentation before the evolution of the bilaterian A-P axis.}, } @article {pmid30262502, year = {2018}, author = {Desforges, JP and Hall, A and McConnell, B and Rosing-Asvid, A and Barber, JL and Brownlow, A and De Guise, S and Eulaers, I and Jepson, PD and Letcher, RJ and Levin, M and Ross, PS and Samarra, F and Víkingson, G and Sonne, C and Dietz, R}, title = {Predicting global killer whale population collapse from PCB pollution.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1373-1376}, doi = {10.1126/science.aat1953}, pmid = {30262502}, issn = {1095-9203}, mesh = {Animals ; *Endangered Species ; *Extinction, Biological ; Immunity/drug effects ; Polychlorinated Biphenyls/*toxicity ; Population ; Reproduction/drug effects ; Water Pollutants, Chemical/*toxicity ; Whale, Killer/immunology/*physiology ; }, abstract = {Killer whales (Orcinus orca) are among the most highly polychlorinated biphenyl (PCB)-contaminated mammals in the world, raising concern about the health consequences of current PCB exposures. Using an individual-based model framework and globally available data on PCB concentrations in killer whale tissues, we show that PCB-mediated effects on reproduction and immune function threaten the long-term viability of >50% of the world's killer whale populations. PCB-mediated effects over the coming 100 years predicted that killer whale populations near industrialized regions, and those feeding at high trophic levels regardless of location, are at high risk of population collapse. Despite a near-global ban of PCBs more than 30 years ago, the world's killer whales illustrate the troubling persistence of this chemical class.}, } @article {pmid30262501, year = {2018}, author = {Monos, TM and McAtee, RC and Stephenson, CRJ}, title = {Arylsulfonylacetamides as bifunctional reagents for alkene aminoarylation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1369-1373}, doi = {10.1126/science.aat2117}, pmid = {30262501}, issn = {1095-9203}, support = {R01 GM096129/GM/NIGMS NIH HHS/United States ; }, abstract = {Alkene aminoarylation with a single, bifunctional reagent is a concise synthetic strategy. We report a catalytic protocol for the addition of arylsulfonylacetamides across electron-rich alkenes with complete anti-Markovnikov regioselectivity and excellent diastereoselectivity to provide 2,2-diarylethylamines. In this process, single-electron alkene oxidation enables carbon-nitrogen bond formation to provide a key benzylic radical poised for a Smiles-Truce 1,5-aryl shift. This reaction is redox-neutral, exhibits broad functional group compatibility, and occurs at room temperature with loss of sulfur dioxide. As this process is driven by visible light, uses readily available starting materials, and demonstrates convergent synthesis, it is well suited for use in a variety of synthetic endeavors.}, } @article {pmid30262500, year = {2018}, author = {Ludwig, JR and Watson, RB and Nasrallah, DJ and Gianino, JB and Zimmerman, PM and Wiscons, RA and Schindler, CS}, title = {Interrupted carbonyl-olefin metathesis via oxygen atom transfer.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1363-1369}, doi = {10.1126/science.aar8238}, pmid = {30262500}, issn = {1095-9203}, support = {R01 GM118644/GM/NIGMS NIH HHS/United States ; }, abstract = {Some of the simplest and most powerful carbon-carbon bond forming strategies take advantage of readily accessible ubiquitous motifs: carbonyls and olefins. Here we report a fundamentally distinct mode of reactivity between carbonyls and olefins that differs from established acid-catalyzed carbonyl-ene, Prins, and carbonyl-olefin metathesis reaction paths. A range of epsilon, zeta-unsaturated ketones undergo Brønsted acid-catalyzed intramolecular cyclization to provide tetrahydrofluorene products via the formation of two new carbon-carbon bonds. Theoretical calculations and accompanying mechanistic studies suggest that this carbocyclization reaction proceeds through the intermediacy of a transient oxetane formed by oxygen atom transfer. The complex polycyclic frameworks in this product class appear as common substructures in organic materials, bioactive natural products, and recently developed pharmaceuticals.}, } @article {pmid30262499, year = {2018}, author = {Carlson, DR and Hickstein, DD and Zhang, W and Metcalf, AJ and Quinlan, F and Diddams, SA and Papp, SB}, title = {Ultrafast electro-optic light with subcycle control.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1358-1363}, doi = {10.1126/science.aat6451}, pmid = {30262499}, issn = {1095-9203}, abstract = {Light sources that are ultrafast and ultrastable enable applications like timing with subfemtosecond precision and control of quantum and classical systems. Mode-locked lasers have often given access to this regime, by using their high pulse energies. We demonstrate an adaptable method for ultrastable control of low-energy femtosecond pulses based on common electro-optic modulation of a continuous-wave laser light source. We show that we can obtain 100-picojoule pulse trains at rates up to 30 gigahertz and demonstrate sub-optical cycle timing precision and useful output spectra spanning the near infrared. Our source enters the few-cycle ultrafast regime without mode locking, and its high speed provides access to nonlinear measurements and rapid transients.}, } @article {pmid30262498, year = {2018}, author = {Brunson, JK and McKinnie, SMK and Chekan, JR and McCrow, JP and Miles, ZD and Bertrand, EM and Bielinski, VA and Luhavaya, H and Oborník, M and Smith, GJ and Hutchins, DA and Allen, AE and Moore, BS}, title = {Biosynthesis of the neurotoxin domoic acid in a bloom-forming diatom.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1356-1358}, pmid = {30262498}, issn = {1095-9203}, support = {P01 ES021921/ES/NIEHS NIH HHS/United States ; T32 GM112584/GM/NIGMS NIH HHS/United States ; }, mesh = {Diatoms/genetics/*metabolism ; *Eutrophication ; Kainic Acid/*analogs & derivatives/chemistry/metabolism ; Multigene Family ; Neurotoxins/*biosynthesis/genetics ; Recombinant Proteins/genetics/metabolism ; }, abstract = {Oceanic harmful algal blooms of Pseudo-nitzschia diatoms produce the potent mammalian neurotoxin domoic acid (DA). Despite decades of research, the molecular basis for its biosynthesis is not known. By using growth conditions known to induce DA production in Pseudo-nitzschia multiseries, we implemented transcriptome sequencing in order to identify DA biosynthesis genes that colocalize in a genomic four-gene cluster. We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA's diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis. Knowledge of the genetic basis for toxin production provides an orthogonal approach to bloom monitoring and enables study of environmental factors that drive oceanic DA production.}, } @article {pmid30262497, year = {2018}, author = {Frye, M and Harada, BT and Behm, M and He, C}, title = {RNA modifications modulate gene expression during development.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1346-1349}, doi = {10.1126/science.aau1646}, pmid = {30262497}, issn = {1095-9203}, support = {R01 GM071440/GM/NIGMS NIH HHS/United States ; F32 CA221007/CA/NCI NIH HHS/United States ; //Medical Research Council/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; //Cancer Research UK/United Kingdom ; RM1 HG008935/HG/NHGRI NIH HHS/United States ; MR/M01939X/1//Medical Research Council/United Kingdom ; }, mesh = {Adenosine/analogs & derivatives/metabolism ; Animals ; Cell Differentiation/genetics ; Disease/genetics ; *Gene Expression Regulation, Developmental ; Humans ; Methyltransferases/genetics ; Mice ; *RNA Processing, Post-Transcriptional ; RNA, Messenger/*metabolism ; RNA, Ribosomal/*metabolism ; RNA, Transfer/*metabolism ; Transcription, Genetic ; }, abstract = {RNA modifications have recently emerged as critical posttranscriptional regulators of gene expression programs. They affect diverse eukaryotic biological processes, and the correct deposition of many of these modifications is required for normal development. Messenger RNA (mRNA) modifications regulate various aspects of mRNA metabolism. For example, N6-methyladenosine (m6A) affects the translation and stability of the modified transcripts, thus providing a mechanism to coordinate the regulation of groups of transcripts during cell state maintenance and transition. Similarly, some modifications in transfer RNAs are essential for RNA structure and function. Others are deposited in response to external cues and adapt global protein synthesis and gene-specific translational accordingly and thereby facilitate proper development.}, } @article {pmid30262496, year = {2018}, author = {Furlong, EEM and Levine, M}, title = {Developmental enhancers and chromosome topology.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1341-1345}, doi = {10.1126/science.aau0320}, pmid = {30262496}, issn = {1095-9203}, support = {R35 GM118147/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chromatin/chemistry ; Chromosomes/chemistry/*ultrastructure ; Embryonic Development/*genetics ; *Enhancer Elements, Genetic ; *Gene Expression Regulation, Developmental ; Humans ; Mice ; *Promoter Regions, Genetic ; Protein Domains ; Transcription, Genetic ; }, abstract = {Developmental enhancers mediate on/off patterns of gene expression in specific cell types at particular stages during metazoan embryogenesis. They typically integrate multiple signals and regulatory determinants to achieve precise spatiotemporal expression. Such enhancers can map quite far-one megabase or more-from the genes they regulate. How remote enhancers relay regulatory information to their target promoters is one of the central mysteries of genome organization and function. A variety of contrasting mechanisms have been proposed over the years, including enhancer tracking, linking, looping, and mobilization to transcription factories. We argue that extreme versions of these mechanisms cannot account for the transcriptional dynamics and precision seen in living cells, tissues, and embryos. We describe emerging evidence for dynamic three-dimensional hubs that combine different elements of the classical models.}, } @article {pmid30262495, year = {2018}, author = {Luo, C and Hajkova, P and Ecker, JR}, title = {Dynamic DNA methylation: In the right place at the right time.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1336-1340}, pmid = {30262495}, issn = {1095-9203}, support = {U19 MH114830/MH/NIMH NIH HHS/United States ; U24 DK112348/DK/NIDDK NIH HHS/United States ; R21 MH112161/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 ES025585/ES/NIEHS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R21 HG009274/HG/NHGRI NIH HHS/United States ; U19 MH114831/MH/NIMH NIH HHS/United States ; R01 MH112763/MH/NIMH NIH HHS/United States ; }, mesh = {5-Methylcytosine/*metabolism ; Aging/*genetics ; Animals ; *DNA Methylation ; Disease/genetics ; Gene Editing ; *Gene Expression Regulation, Developmental ; Humans ; *Memory ; Neoplasms/genetics ; Single-Cell Analysis ; Transcription Factors/metabolism ; Transcription, Genetic ; }, abstract = {The classical model of cytosine DNA methylation (the presence of 5-methylcytosine, 5mC) regulation depicts this covalent modification as a stable repressive regulator of promoter activity. However, whole-genome analysis of 5mC reveals widespread tissue- and cell type-specific patterns and pervasive dynamics during mammalian development. Here we review recent findings that delineate 5mC functions in developmental stages and diverse genomic compartments as well as discuss the molecular mechanisms that connect transcriptional regulation and 5mC. Beyond the newly appreciated dynamics, regulatory roles for 5mC have been suggested in new biological contexts, such as learning and memory or aging. The use of new single-cell measurement techniques and precise editing tools will enable functional analyses of 5mC in gene expression, clarifying its role in various biological processes.}, } @article {pmid30262494, year = {2018}, author = {Yadav, T and Quivy, JP and Almouzni, G}, title = {Chromatin plasticity: A versatile landscape that underlies cell fate and identity.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1332-1336}, doi = {10.1126/science.aat8950}, pmid = {30262494}, issn = {1095-9203}, mesh = {Animals ; Chromatin/metabolism/*physiology/ultrastructure ; *Chromatin Assembly and Disassembly ; Histones/metabolism ; Humans ; Molecular Chaperones/metabolism ; Pluripotent Stem Cells/metabolism/*physiology ; }, abstract = {During development and throughout life, a variety of specialized cells must be generated to ensure the proper function of each tissue and organ. Chromatin plays a key role in determining cellular state, whether totipotent, pluripotent, multipotent, or differentiated. We highlight chromatin dynamics involved in the generation of pluripotent stem cells as well as their influence on cell fate decision and reprogramming. We focus on the capacity of histone variants, chaperones, modifications, and heterochromatin factors to influence cell identity and its plasticity. Recent technological advances have provided tools to elucidate the underlying chromatin dynamics for a better understanding of normal development and pathological conditions, with avenues for potential therapeutic application.}, } @article {pmid30262493, year = {2018}, author = {Purnell, BA and Mao, S and Zahn, LM}, title = {Forces behind form.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1330-1331}, doi = {10.1126/science.361.6409.1330}, pmid = {30262493}, issn = {1095-9203}, mesh = {Animals ; Cell Physiological Phenomena ; Dogs ; Gene Expression Regulation, Developmental ; Growth and Development/*genetics ; Histones/metabolism ; *Models, Anatomic ; }, } @article {pmid30262492, year = {2018}, author = {Ritchie, EG and Smith, BP and van Eeden, LM and Nimmo, DG}, title = {Species definitions shape policy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1324}, doi = {10.1126/science.aav3437}, pmid = {30262492}, issn = {1095-9203}, mesh = {Animals ; Australia ; Biodiversity ; Conservation of Natural Resources ; Wolves/*classification ; }, } @article {pmid30262491, year = {2018}, author = {Vink, JM and Schellekens, A}, title = {Relating addiction and psychiatric disorders.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1323-1324}, doi = {10.1126/science.aav3928}, pmid = {30262491}, issn = {1095-9203}, mesh = {Behavior, Addictive/*psychology ; Humans ; Mental Disorders/*psychology ; Substance-Related Disorders/psychology ; }, } @article {pmid30262490, year = {2018}, author = {Zamudio, KR and Kellner, A and Serejo, C and de Britto, MR and Castro, CB and Buckup, PA and Pires, DO and Couri, M and Kury, AB and Cardoso, IA and Monné, ML and Pombal, J and Patiu, CM and Padula, V and Pimenta, AD and Ventura, CRR and Hajdu, E and Zanol, J and Bruna, EM and Fitzpatrick, J and Rocha, LA}, title = {Lack of science support fails Brazil.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1322-1323}, doi = {10.1126/science.aav3296}, pmid = {30262490}, issn = {1095-9203}, mesh = {Brazil ; *Science ; }, } @article {pmid30262489, year = {2018}, author = {Berg, J}, title = {Editorial expression of concern.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1322}, doi = {10.1126/science.aav4528}, pmid = {30262489}, issn = {1095-9203}, } @article {pmid30262488, year = {2018}, author = {Song, M and Vogelstein, B and Giovannucci, EL and Willett, WC and Tomasetti, C}, title = {Cancer prevention: Molecular and epidemiologic consensus.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1317-1318}, pmid = {30262488}, issn = {1095-9203}, support = {R01 CA050385/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; UM1 CA176726/CA/NCI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; K99 CA215314/CA/NCI NIH HHS/United States ; R00 CA215314/CA/NCI NIH HHS/United States ; }, mesh = {Global Health ; Humans ; Neoplasms/*epidemiology/genetics/*prevention & control/therapy ; }, } @article {pmid30262487, year = {2018}, author = {Torres-Company, V}, title = {Electro-optic combs rise above the noise.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1316}, doi = {10.1126/science.aau7507}, pmid = {30262487}, issn = {1095-9203}, mesh = {*Electronics ; *Equipment Design ; Optics and Photonics ; }, } @article {pmid30262486, year = {2018}, author = {Aguirre-Ghiso, JA}, title = {How dormant cancer persists and reawakens.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1314-1315}, doi = {10.1126/science.aav0191}, pmid = {30262486}, issn = {1095-9203}, support = {R01 CA109182/CA/NCI NIH HHS/United States ; R01 CA216248/CA/NCI NIH HHS/United States ; R01 CA218024/CA/NCI NIH HHS/United States ; }, mesh = {Humans ; *Neoplasms ; }, } @article {pmid30262485, year = {2018}, author = {Ford, A and Horn, S}, title = {Above and below the Maya forest.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1313-1314}, doi = {10.1126/science.aav0887}, pmid = {30262485}, issn = {1095-9203}, mesh = {*Forests ; *Trees ; }, } @article {pmid30262484, year = {2018}, author = {Ahmad, K and Henikoff, S}, title = {No strand left behind.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1311-1312}, doi = {10.1126/science.aav0871}, pmid = {30262484}, issn = {1095-9203}, mesh = {*DNA Replication ; *Histones ; }, } @article {pmid30262483, year = {2018}, author = {Arendt, D}, title = {Hox genes and body segmentation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1310-1311}, doi = {10.1126/science.aav0692}, pmid = {30262483}, issn = {1095-9203}, mesh = {Body Patterning/*genetics ; Gene Expression Regulation, Developmental ; *Genes, Homeobox ; Homeodomain Proteins/genetics ; }, } @article {pmid30262482, year = {2018}, author = {Pohnert, G and Poulin, RX and Baumeister, TUH}, title = {The making of a plankton toxin.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1308-1309}, doi = {10.1126/science.aau9067}, pmid = {30262482}, issn = {1095-9203}, mesh = {Animals ; *Plankton ; *Toxins, Biological ; Zooplankton ; }, } @article {pmid30262481, year = {2018}, author = {Wade, L}, title = {Bridging the gap.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1304-1307}, doi = {10.1126/science.361.6409.1304}, pmid = {30262481}, issn = {1095-9203}, mesh = {Anthropology/*methods ; Ethnic Groups/*genetics ; Genomics/*education ; Humans ; }, } @article {pmid30262480, year = {2018}, author = {Service, RF}, title = {Cool paint job fights solar warmth.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1303}, doi = {10.1126/science.361.6409.1303}, pmid = {30262480}, issn = {1095-9203}, } @article {pmid30262479, year = {2018}, author = {Leslie, M}, title = {'Old' genome editors might treat mitochondrial diseases.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1302}, doi = {10.1126/science.361.6409.1302}, pmid = {30262479}, issn = {1095-9203}, mesh = {Animals ; Clustered Regularly Interspaced Short Palindromic Repeats ; DNA, Mitochondrial/*genetics ; Gene Editing/*methods ; Genetic Therapy/*methods ; Genome ; Humans ; Mitochondrial Diseases/*therapy ; Mutation ; RNA, Guide ; Transcription Activator-Like Effector Nucleases/*genetics ; Viruses ; Zinc Finger Nucleases/*genetics ; }, } @article {pmid30262478, year = {2018}, author = {Chen, S}, title = {Atomic arrays power quantum computers.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1300-1301}, doi = {10.1126/science.361.6409.1300}, pmid = {30262478}, issn = {1095-9203}, } @article {pmid30262477, year = {2018}, author = {Mervis, J and Kaiser, J}, title = {NSF issues sexual harassment policy as NIH promises action.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1299-1300}, doi = {10.1126/science.361.6409.1299}, pmid = {30262477}, issn = {1095-9203}, mesh = {Financing, Organized/*ethics ; Humans ; National Institutes of Health (U.S.) ; Policy ; *Sexual Harassment ; United States ; }, } @article {pmid30262476, year = {2018}, author = {Mlot, C}, title = {Classic wolf-moose study to be restarted on Isle Royale.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1298-1299}, doi = {10.1126/science.361.6409.1298}, pmid = {30262476}, issn = {1095-9203}, mesh = {Animals ; Climate Change ; *Food Chain ; Inbreeding ; Michigan ; Population ; *Ruminants ; *Wolves ; }, } @article {pmid30262474, year = {2018}, author = {Barbuy, B}, title = {Crisis in Brazil.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1293}, doi = {10.1126/science.aav4152}, pmid = {30262474}, issn = {1095-9203}, } @article {pmid30262473, year = {2018}, author = {Stewart, C and Leshchiner, I and Hess, J and Getz, G}, title = {Comment on "DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {}, doi = {10.1126/science.aas9824}, pmid = {30262473}, issn = {1095-9203}, mesh = {*Artifacts ; *DNA Damage ; High-Throughput Nucleotide Sequencing ; Humans ; Neoplasms/genetics ; Sequence Analysis, DNA ; }, abstract = {Chen et al (Reports, 17 February 2017, p. 752) highlight an important problem of sequencing artifacts caused by DNA damage at the time of sample processing. However, their manuscript contains several errors that led the authors to incorrect conclusions. Moreover, the same sequencing artifacts were previously described and mitigated in The Cancer Genome Atlas and other published sequencing projects.}, } @article {pmid30262472, year = {2018}, author = {Albrengues, J and Shields, MA and Ng, D and Park, CG and Ambrico, A and Poindexter, ME and Upadhyay, P and Uyeminami, DL and Pommier, A and Küttner, V and Bružas, E and Maiorino, L and Bautista, C and Carmona, EM and Gimotty, PA and Fearon, DT and Chang, K and Lyons, SK and Pinkerton, KE and Trotman, LC and Goldberg, MS and Yeh, JT and Egeblad, M}, title = {Neutrophil extracellular traps produced during inflammation awaken dormant cancer cells in mice.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {}, doi = {10.1126/science.aao4227}, pmid = {30262472}, issn = {1095-9203}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; R01 CA137050/CA/NCI NIH HHS/United States ; P30 ES023513/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Carcinogenesis/*metabolism ; DNA/metabolism ; Extracellular Traps/*enzymology ; Humans ; Inflammation/chemically induced/microbiology ; Integrin alpha3beta1/metabolism ; Lamins/*metabolism ; Leukocyte Elastase/metabolism ; Lipopolysaccharides ; Lung/pathology ; Lung Neoplasms/*pathology ; MCF-7 Cells ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Inbred BALB C ; Neoplasms, Experimental/pathology ; Neutrophils/*enzymology ; Pneumonia/chemically induced/microbiology/*pathology ; Pneumonia, Bacterial/etiology/pathology ; Protein-Arginine Deiminases/antagonists & inhibitors/metabolism ; Proteolysis ; Rats ; Signal Transduction ; Smoking ; Tobacco ; }, abstract = {Cancer cells from a primary tumor can disseminate to other tissues, remaining dormant and clinically undetectable for many years. Little is known about the cues that cause these dormant cells to awaken, resume proliferating, and develop into metastases. Studying mouse models, we found that sustained lung inflammation caused by tobacco smoke exposure or nasal instillation of lipopolysaccharide converted disseminated, dormant cancer cells to aggressively growing metastases. Sustained inflammation induced the formation of neutrophil extracellular traps (NETs), and these were required for awakening dormant cancer. Mechanistic analysis revealed that two NET-associated proteases, neutrophil elastase and matrix metalloproteinase 9, sequentially cleaved laminin. The proteolytically remodeled laminin induced proliferation of dormant cancer cells by activating integrin α3β1 signaling. Antibodies against NET-remodeled laminin prevented awakening of dormant cells. Therapies aimed at preventing dormant cell awakening could potentially prolong the survival of cancer patients.}, } @article {pmid30262471, year = {2018}, author = {Beltrán-Sánchez, H and Austad, SN and Finch, CE}, title = {Comment on "The plateau of human mortality: Demography of longevity pioneers".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {}, doi = {10.1126/science.aav1200}, pmid = {30262471}, issn = {1095-9203}, mesh = {Aging ; *Demography ; Humans ; Life Expectancy ; *Longevity ; Mortality ; }, abstract = {Barbi et al (Reports, 29 June 2018, p. 1459) reported that human mortality rate reached a "plateau" after the age of 105, suggesting there may be no limit to human longevity. We show, using their data, that potential lifespans cannot increase much beyond the current 122 years unless future biomedical advances alter the intrinsic rate of human aging.}, } @article {pmid30262470, year = {2018}, author = {Chen, L and Liu, P and Evans, TC and Ettwiller, LM}, title = {Response to Comment on "DNA damage is a pervasive cause of sequencing errors, directly confounding variant identification".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {}, doi = {10.1126/science.aat0958}, pmid = {30262470}, issn = {1095-9203}, mesh = {*DNA Damage ; Databases, Genetic ; Genome ; High-Throughput Nucleotide Sequencing ; Mutation ; Sequence Analysis, DNA ; *Software ; }, abstract = {Following the Comment of Stewart et al, we repeated our analysis on sequencing runs from The Cancer Genome Atlas (TCGA) using their suggested parameters. We found signs of oxidative damage in all sequence contexts and irrespective of the sequencing date, reaffirming that DNA damage affects mutation-calling pipelines in their ability to accurately identify somatic variations.}, } @article {pmid30262469, year = {2018}, author = {Canuto, MA and Estrada-Belli, F and Garrison, TG and Houston, SD and Acuña, MJ and Kováč, M and Marken, D and Nondédéo, P and Auld-Thomas, L and Castanet, C and Chatelain, D and Chiriboga, CR and Drápela, T and Lieskovský, T and Tokovinine, A and Velasquez, A and Fernández-Díaz, JC and Shrestha, R}, title = {Ancient lowland Maya complexity as revealed by airborne laser scanning of northern Guatemala.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {}, doi = {10.1126/science.aau0137}, pmid = {30262469}, issn = {1095-9203}, abstract = {Lowland Maya civilization flourished in the tropical region of the Yucatan peninsula and environs for more than 2500 years (~1000 BCE to 1500 CE). Known for its sophistication in writing, art, architecture, astronomy, and mathematics, Maya civilization still poses questions about the nature of its cities and surrounding populations because of its location in an inaccessible forest. In 2016, an aerial lidar survey across 2144 square kilometers of northern Guatemala mapped natural terrain and archaeological features over several distinct areas. We present results from these data, revealing interconnected urban settlement and landscapes with extensive infrastructural development. Studied through a joint international effort of interdisciplinary teams sharing protocols, this lidar survey compels a reevaluation of Maya demography, agriculture, and political economy and suggests future avenues of field research.}, } @article {pmid30261922, year = {2018}, author = {Roberts-Crowley, ML and Rittenhouse, AR}, title = {Modulation of CaV1.3b L-type calcium channels by M1 muscarinic receptors varies with CaVβ subunit expression.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {681}, pmid = {30261922}, issn = {1756-0500}, support = {R01 NS034195/NS/NINDS NIH HHS/United States ; T32 NS007366/NS/NINDS NIH HHS/United States ; NS-34195//National Institute of Neurological Disorders and Stroke/ ; TS-NS07366-09//National Institutes of Health/ ; }, mesh = {Calcium ; Calcium Channels, L-Type/*physiology ; HEK293 Cells ; Humans ; Receptor, Muscarinic M1/*physiology ; Receptors, Dopamine D2 ; Receptors, G-Protein-Coupled/*physiology ; }, abstract = {OBJECTIVES: We examined whether two G protein-coupled receptors (GPCRs), muscarinic M1 receptors (M1Rs) and dopaminergic D2 receptors (D2Rs), utilize endogenously released fatty acid to inhibit L-type Ca2+ channels, CaV1.3. HEK-293 cells, stably transfected with M1Rs, were used to transiently transfect D2Rs and CaV1.3b with different CaVβ-subunits, allowing for whole-cell current measurement from a pure channel population.

RESULTS: M1R activation with Oxotremorine-M inhibited currents from CaV1.3b coexpressed with α2δ-1 and a β1b, β2a, β3, or β4-subunit. Surprisingly, the magnitude of inhibition was less with β2a than with other CaVβ-subunits. Normalizing currents revealed kinetic changes after modulation with β1b, β3, or β4, but not β2a-containing channels. We then examined if D2Rs modulate CaV1.3b when expressed with different CaVβ-subunits. Stimulation with quinpirole produced little inhibition or kinetic changes for CaV1.3b coexpressed with β2a or β3. However, quinpirole inhibited N-type Ca2+ currents in a concentration-dependent manner, indicating functional expression of D2Rs. N-current inhibition by quinpirole was voltage-dependent and independent of phospholipase A2 (PLA2), whereas a PLA2 antagonist abolished M1R-mediated N-current inhibition. These findings highlight the specific regulation of Ca2+ channels by different GPCRs. Moreover, tissue-specific and/or cellular localization of CaV1.3b with different CaVβ-subunits could fine tune the response of Ca2+ influx following GPCR activation.}, } @article {pmid30261913, year = {2018}, author = {Yang, L and Jin, Y and Huang, W and Sun, Q and Liu, F and Huang, X}, title = {Full-length transcriptome sequences of ephemeral plant Arabidopsis pumila provides insight into gene expression dynamics during continuous salt stress.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {717}, pmid = {30261913}, issn = {1471-2164}, mesh = {Arabidopsis/drug effects/*genetics ; Arabidopsis Proteins/drug effects/*genetics ; China ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant/drug effects ; Gene Regulatory Networks ; Plant Leaves/drug effects/genetics ; Salinity ; Sequence Analysis, RNA ; Sodium Chloride/*pharmacology ; Stress, Physiological ; }, abstract = {BACKGROUND: Arabidopsis pumila is native to the desert region of northwest China and it is extraordinarily well adapted to the local semi-desert saline soil, thus providing a candidate plant system for environmental adaptation and salt-tolerance gene mining. However, understanding of the salt-adaptation mechanism of this species is limited because of genomic sequences scarcity. In the present study, the transcriptome profiles of A. pumila leaf tissues treated with 250 mM NaCl for 0, 0.5, 3, 6, 12, 24 and 48 h were analyzed using a combination of second-generation sequencing (SGS) and third-generation single-molecule real-time (SMRT) sequencing.

RESULTS: Correction of SMRT long reads by SGS short reads resulted in 59,328 transcripts. We found 8075 differentially expressed genes (DEGs) between salt-stressed tissues and controls, of which 483 were transcription factors and 1157 were transport proteins. Most DEGs were activated within 6 h of salt stress and their expression stabilized after 48 h; the number of DEGs was greatest within 12 h of salt stress. Gene annotation and functional analyses revealed that expression of genes associated with the osmotic and ionic phases rapidly and coordinately changed during the continuous salt stress in this species, and salt stress-related categories were highly enriched among these DEGs, including oxidation-reduction, transmembrane transport, transcription factor activity and ion channel activity. Orphan, MYB, HB, bHLH, C3H, PHD, bZIP, ARF and NAC TFs were most enriched in DEGs; ABCB1, CLC-A, CPK30, KEA2, KUP9, NHX1, SOS1, VHA-A and VP1 TPs were extensively up-regulated in salt-stressed samples, suggesting that they play important roles in slat tolerance. Importantly, further experimental studies identified a mitogen-activated protein kinase (MAPK) gene MAPKKK18 as continuously up-regulated throughout salt stress, suggesting its crucial role in salt tolerance. The expression patterns of the salt-responsive 24 genes resulted from quantitative real-time PCR were basically consistent with their transcript abundance changes identified by RNA-Seq.

CONCLUSION: The full-length transcripts generated in this study provide a more accurate depiction of gene transcription of A. pumila. We identified potential genes involved in salt tolerance of A. pumila. These data present a genetic resource and facilitate better understanding of salt-adaptation mechanism for ephemeral plants.}, } @article {pmid30261908, year = {2018}, author = {Dank, A and Smid, EJ and Notebaart, RA}, title = {CRISPR-Cas genome engineering of esterase activity in Saccharomyces cerevisiae steers aroma formation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {682}, pmid = {30261908}, issn = {1756-0500}, mesh = {*CRISPR-Cas Systems ; Carboxylic Ester Hydrolases ; Clustered Regularly Interspaced Short Palindromic Repeats ; Esterases/*genetics/metabolism ; Fermentation ; *Gene Editing ; Mutation ; *Odorants ; Saccharomyces cerevisiae/*enzymology ; Saccharomyces cerevisiae Proteins ; }, abstract = {OBJECTIVE: Saccharomyces cerevisiae is used worldwide for the production of ale-type beers. This yeast is responsible for the production of the characteristic fruity aroma compounds. Esters constitute an important group of aroma active secondary metabolites produced by S. cerevisiae. Previous work suggests that esterase activity, which results in ester degradation, may be the key factor determining the abundance of fruity aroma compounds. Here, we test this hypothesis by deletion of two S. cerevisiae esterases, IAH1 and TIP1, using CRISPR-Cas9 genome editing and by studying the effect of these deletions on esterase activity and extracellular ester pools.

RESULTS: Saccharomyces cerevisiae mutants were constructed lacking esterase IAH1 and/or TIP1 using CRISPR-Cas9 genome editing. Esterase activity using 5-(6)-carboxyfluorescein diacetate (cFDA) as substrate was found to be significantly lower for ΔIAH1 and ΔIAH1ΔTIP1 mutants compared to wild type (WT) activity (P < 0.05 and P < 0.001, respectively). As expected, we observed an increase in relative abundance of acetate and ethyl esters and an increase in ethyl esters in ΔIAH1 and ΔTIP1, respectively. Interestingly, the double gene disruption mutant ΔIAH1ΔTIP1 showed an aroma profile comparable to WT levels, suggesting the existence and activation of a complex regulatory mechanism to compensate multiple genomic alterations in aroma metabolism.}, } @article {pmid30261880, year = {2018}, author = {Sunagar, K and Columbus-Shenkar, YY and Fridrich, A and Gutkovich, N and Aharoni, R and Moran, Y}, title = {Cell type-specific expression profiling unravels the development and evolution of stinging cells in sea anemone.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {108}, pmid = {30261880}, issn = {1741-7007}, abstract = {BACKGROUND: Cnidocytes are specialized cells that define the phylum Cnidaria. They possess an "explosive" organelle called cnidocyst that is important for prey capture and anti-predator defense. An extraordinary morphological and functional complexity of the cnidocysts has inspired numerous studies to investigate their structure and development. However, the transcriptomes of the cells bearing these unique organelles are yet to be characterized, impeding our understanding of the genetic basis of their biogenesis.

RESULTS: In this study, we generated a nematocyte reporter transgenic line of the sea anemone Nematostella vectensis using the CRISPR/Cas9 system. By using a fluorescence-activated cell sorter (FACS), we have characterized cell type-specific transcriptomic profiles of various stages of cnidocyte maturation and showed that nematogenesis (the formation of functional cnidocysts) is underpinned by dramatic shifts in the spatiotemporal gene expression. Among the genes identified as upregulated in cnidocytes were Cnido-Jun and Cnido-Fos1-cnidarian-specific paralogs of the highly conserved c-Jun and c-Fos proteins of the stress-induced AP-1 transcriptional complex. The knockdown of the cnidocyte-specific c-Jun homolog by microinjection of morpholino antisense oligomer results in disruption of normal nematogenesis.

CONCLUSIONS: Here, we show that the majority of upregulated genes and enriched biochemical pathways specific to cnidocytes are uncharacterized, emphasizing the need for further functional research on nematogenesis. The recruitment of the metazoan stress-related transcription factor c-Fos/c-Jun complex into nematogenesis highlights the evolutionary ingenuity and novelty associated with the formation of these highly complex, enigmatic, and phyletically unique organelles. Thus, we provide novel insights into the biology, development, and evolution of cnidocytes.}, } @article {pmid30261869, year = {2018}, author = {Allman, BP and Kielland, K and Wagner, D}, title = {Leaf herbivory by insects during summer reduces overwinter browsing by moose.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {38}, pmid = {30261869}, issn = {1472-6785}, support = {DEB 1026415//National Science Foundation/International ; }, abstract = {BACKGROUND: Damage to plants by herbivores potentially affects the quality and quantity of the plant tissue available to other herbivore taxa that utilize the same host plants at a later time. This study addresses the indirect effects of insect herbivores on mammalian browsers, a particularly poorly-understood class of interactions. Working in the Alaskan boreal forest, we investigated the indirect effects of insect damage to Salix interior leaves during the growing season on the consumption of browse by moose during winter, and on quantity and quality of browse production.

RESULTS: Treatment with insecticide reduced leaf mining damage by the willow leaf blotch miner, Micrurapteryx salicifoliella, and increased both the biomass and proportion of the total production of woody tissue browsed by moose. Salix interior plants with experimentally-reduced insect damage produced significantly more stem biomass than controls, but did not differ in stem quality as indicated by nitrogen concentration or protein precipitation capacity, an assay of the protein-binding activity of tannins.

CONCLUSIONS: Insect herbivory on Salix, including the outbreak herbivore M. salicifoliella, affected the feeding behavior of moose. The results demonstrate that even moderate levels of leaf damage by insects can have surprisingly strong impacts on stem production and influence the foraging behavior of distantly related taxa browsing on woody tissue months after leaves have dropped.}, } @article {pmid30261844, year = {2018}, author = {Cao, FY and DeFalco, TA and Moeder, W and Li, B and Gong, Y and Liu, XM and Taniguchi, M and Lumba, S and Toh, S and Shan, L and Ellis, B and Desveaux, D and Yoshioka, K}, title = {Arabidopsis ETHYLENE RESPONSE FACTOR 8 (ERF8) has dual functions in ABA signaling and immunity.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {211}, pmid = {30261844}, issn = {1471-2229}, support = {A-1795//Robert A. Welch foundation/ ; }, mesh = {Abscisic Acid/*metabolism ; Amino Acid Motifs ; Arabidopsis/cytology/*physiology ; Arabidopsis Proteins/genetics/immunology/*metabolism ; Cell Death ; Gene Expression Regulation, Plant ; Mitogen-Activated Protein Kinases/genetics/metabolism ; Mutation ; Phosphorylation ; Plant Diseases ; Plant Immunity/*physiology ; Plants, Genetically Modified ; Pseudomonas syringae/pathogenicity ; Repressor Proteins/genetics/immunology/*metabolism ; Salicylic Acid/metabolism ; Serine/genetics ; Signal Transduction ; Tobacco/genetics ; }, abstract = {BACKGROUND: ETHYLENE RESPONSE FACTOR (ERF) 8 is a member of one of the largest transcription factor families in plants, the APETALA2/ETHYLENE RESPONSIVE FACTOR (AP2/ERF) superfamily. Members of this superfamily have been implicated in a wide variety of processes such as development and environmental stress responses.

RESULTS: In this study we demonstrated that ERF8 is involved in both ABA and immune signaling. ERF8 overexpression induced programmed cell death (PCD) in Arabidopsis and Nicotiana benthamiana. This PCD was salicylic acid (SA)-independent, suggesting that ERF8 acts downstream or independent of SA. ERF8-induced PCD was abolished by mutations within the ERF-associated amphiphilic repression (EAR) motif, indicating ERF8 induces cell death through its transcriptional repression activity. Two immunity-related mitogen-activated protein kinases, MITOGEN-ACTIVATED PROTEIN KINASE 4 (MPK4) and MPK11, were identified as ERF8-interacting proteins and directly phosphorylated ERF8 in vitro. Four putative MPK phosphorylation sites were identified in ERF8, one of which (Ser103) was determined to be the predominantly phosphorylated residue in vitro, while mutation of all four putative phosphorylation sites partially suppressed ERF8-induced cell death in N. benthamiana. Genome-wide transcriptomic analysis and pathogen growth assays confirmed a positive role of ERF8 in mediating immunity, as ERF8 knockdown or overexpression lines conferred compromised or enhanced resistance against the hemibiotrophic bacterial pathogen Pseudomonas syringae, respectively.

CONCLUSIONS: Together these data reveal that the ABA-inducible transcriptional repressor ERF8 has dual roles in ABA signaling and pathogen defense, and further highlight the complex influence of ABA on plant-microbe interactions.}, } @article {pmid30261842, year = {2018}, author = {Sanderson, ND and Street, TL and Foster, D and Swann, J and Atkins, BL and Brent, AJ and McNally, MA and Oakley, S and Taylor, A and Peto, TEA and Crook, DW and Eyre, DW}, title = {Real-time analysis of nanopore-based metagenomic sequencing from infected orthopaedic devices.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {714}, pmid = {30261842}, issn = {1471-2164}, mesh = {Bacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/analysis ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Joint Prosthesis/*microbiology ; Metagenomics/*methods ; Nanopores ; Pilot Projects ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Prosthetic joint infections are clinically difficult to diagnose and treat. Previously, we demonstrated metagenomic sequencing on an Illumina MiSeq replicates the findings of current gold standard microbiological diagnostic techniques. Nanopore sequencing offers advantages in speed of detection over MiSeq. Here, we report a real-time analytical pathway for Nanopore sequence data, designed for detecting bacterial composition of prosthetic joint infections but potentially useful for any microbial sequencing, and compare detection by direct-from-clinical-sample metagenomic nanopore sequencing with Illumina sequencing and standard microbiological diagnostic techniques.

RESULTS: DNA was extracted from the sonication fluids of seven explanted orthopaedic devices, and additionally from two culture negative controls, and was sequenced on the Oxford Nanopore Technologies MinION platform. A specific analysis pipeline was assembled to overcome the challenges of identifying the true infecting pathogen, given high levels of host contamination and unavoidable background lab and kit contamination. The majority of DNA classified (> 90%) was host contamination and discarded. Using negative control filtering thresholds, the species identified corresponded with both routine microbiological diagnosis and MiSeq results. By analysing sequences in real time, causes of infection were robustly detected within minutes from initiation of sequencing.

CONCLUSIONS: We demonstrate a novel, scalable pipeline for real-time analysis of MinION sequence data and use of this pipeline to show initial proof of concept that metagenomic MinION sequencing can provide rapid, accurate diagnosis for prosthetic joint infections. The high proportion of human DNA in prosthetic joint infection extracts prevents full genome analysis from complete coverage, and methods to reduce this could increase genome depth and allow antimicrobial resistance profiling. The nine samples sequenced in this pilot study have shown a proof of concept for sequencing and analysis that will enable us to investigate further sequencing to improve specificity and sensitivity.}, } @article {pmid30261838, year = {2018}, author = {Farlow, J and Bolkvadze, D and Leshkasheli, L and Kusradze, I and Kotorashvili, A and Kotaria, N and Balarjishvili, N and Kvachadze, L and Nikolich, M and Kutateladze, M}, title = {Correction to: Genomic characterization of three novel Basilisk-like phages infecting Bacillus anthracis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {713}, pmid = {30261838}, issn = {1471-2164}, abstract = {Following the publication of this article [1], the authors noted two typographical errors: one in Table 1 with regard to the location of the Basilisk Phage, which was incorrectly captured as "Kutaisis, country of Georgia Utah, USA" but should be "Utah, USA".}, } @article {pmid30261835, year = {2018}, author = {Polouliakh, N and Horton, P and Shibanai, K and Takata, K and Ludwig, V and Ghosh, S and Kitano, H}, title = {Sequence homology in eukaryotes (SHOE): interactive visual tool for promoter analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {715}, pmid = {30261835}, issn = {1471-2164}, mesh = {Animals ; Binding Sites ; Computational Biology/*methods ; DNA/chemistry/*metabolism ; Evolution, Molecular ; Gene Expression Regulation ; Humans ; Internet ; Mice ; Position-Specific Scoring Matrices ; *Promoter Regions, Genetic ; Rats ; Sequence Homology, Nucleic Acid ; Software ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Microarray and DNA-sequencing based technologies continue to produce enormous amounts of data on gene expression. This data has great potential to illuminate our understanding of biology and medicine, but the data alone is of limited value without computational tools to allow human investigators to visualize and interpret it in the context of their problem of interest.

RESULTS: We created a web server called SHOE that provides an interactive, visual presentation of the available evidence of transcriptional regulation and gene co-expression to facilitate its exploration and interpretation. SHOE predicts the likely transcription factor binding sites in orthologous promoters of humans, mice, and rats using the combined information of 1) transcription factor binding preferences (position-specific scoring matrix (PSSM) libraries such as Transfac32, Jaspar, HOCOMOCO, ChIP-seq, SELEX, PBM, and iPS-reprogramming factor), 2) evolutionary conservation of putative binding sites in orthologous promoters, and 3) co-expression tendencies of gene pairs based on 1,714 normal human cells selected from the Gene Expression Omnibus Database.

CONCLUSION: SHOE enables users to explore potential interactions between transcription factors and target genes via multiple data views, discover transcription factor binding motifs on top of gene co-expression, and visualize genes as a network of gene and transcription factors on its native gadget GeneViz, the CellDesigner pathway analyzer, and the Reactome database to search the pathways involved. As we demonstrate here when using the CREB1 and Nf-κB datasets, SHOE can reliably identify experimentally verified interactions and predict plausible novel ones, yielding new biological insights into the gene regulatory mechanisms involved. SHOE comes with a manual describing how to run it on a local PC or via the Garuda platform (www.garuda-alliance.org), where it joins other popular gadgets such as the CellDesigner pathway analyzer and the Reactome database, as part of analysis workflows to meet the growing needs of molecular biologists and medical researchers. SHOE is available from the following URL http://ec2-54-150-223-65.ap-northeast-1.compute.amazonaws.com A video demonstration of SHOE can be found here: https://www.youtube.com/watch?v=qARinNb9NtE.}, } @article {pmid30261834, year = {2018}, author = {Wang, R and Li, L and Huang, T and Huang, Y and Huang, W and Yang, X and Lei, A and Chen, M}, title = {Phylogenetic, comparative genomic and structural analyses of human Streptococcus agalactiae ST485 in China.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {716}, pmid = {30261834}, issn = {1471-2164}, support = {31460695//National Natural Science Foundation of China/ ; AA17204081-3//Guangxi innovation-driven development special funds/ ; 2016GXNSFDA380020//Guangxi Natural Science Foundation/ ; 2016-2018//the funds of Guangxi Key Laboratory for Aquatic Genetic Breeding and Healthy Aquaculture/ ; }, mesh = {Animals ; Cattle ; Cattle Diseases/microbiology ; China ; Evolution, Molecular ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Humans ; Phylogeny ; Recombination, Genetic ; Sequence Analysis, DNA/*methods ; Streptococcal Infections/*microbiology/veterinary ; Streptococcus agalactiae/*classification/genetics/isolation & purification ; }, abstract = {BACKGROUND: Streptococcus agalactiae (Group B Streptococcus, GBS) is a common bacteria species infecting both human and bovine. Previous studies have shown that the GBS isolated from human and bovine are mostly unrelated and belong to separate populations. However, recently, the bovine GBS CC103 has become the dominant epidemic strain and frequently isolated from human patients. In particular, the ST485 GBS, a member of CC103, has become the new dominant ST in China and exhibited very high pathogenicity. This phenomenon is not consistent with the established understanding about the relationship between bovine and human GBS, which needs to be re-investigated.

RESULTS: The genome-based phylogenetic analysis showed that the human and bovine GBS CC103 strains had very close genetic relationship and they were alternately distributed on the evolutionary tree. CC103 strains evolved into several branches, including the ST485, which exhibited high pathogenicity and specifically infected human. Compared to other CC103 strains, the ST485 lacked Lac.2 gene structure and acquired the CadDX gene structure in their genomes.

CONCLUSIONS: Our results indicate that GBS CC103 could propagate across human and bovine, and GBS ST485 might evolve from the ST103 that could infect both human and bovine. Moreover, the recombination of Lac.2 and CadDX gene structures might play an important role in the formation of highly pathogenic ST485 in China.}, } @article {pmid30259678, year = {2018}, author = {Ballen-Segura, M and Catalan, J and Felip, M}, title = {Experimental evidence of the quantitative relationship between the prokaryote ingestion rate and the food vacuole content in mixotrophic phytoflagellates.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {704-710}, doi = {10.1111/1758-2229.12696}, pmid = {30259678}, issn = {1758-2229}, abstract = {The verification that many phytoflagellates ingest prokaryotes has changed the view of the microbial loop in aquatic ecosystems. Still, progress is limited because the phagotrophic activity is difficult to quantify in natural assemblages. Linking the food vacuole content in protist with the ingestion rate of prokaryotes would provide a crucial step forward. In this study, using the catalysed reporter deposition - fluorescence in situ hybridization protocol (CARD-FISH), which allows the visualization of labelled prokaryotes inside protists without relying on incubation procedures, we experimentally relate the food vacuole content of prokaryotes (Vc) to the population-averaged ingestion rates (Ir) estimated using bacteria-size fluorescent microspheres. The two variables relate according to the equation Ir = 7.52 Vc0.9 , which indicates a prokaryote half-life of about 6 min in the protist vacuole. Five mixotrophic flagellate species from natural and culture populations were evaluated seven times during 24 h; they provided a broad range of average vacuole content (0.01 to 2.02 prokaryote protist-1) and ingestion rates (0.18 to 23 prokaryote protist-1 h-1). Consequently, the relationship found can be applied to quantify the mixotrophy activity in a large variety of field and experimental studies.}, } @article {pmid30259625, year = {2018}, author = {Moreno, E and Lenuzzi, M and Rödelsperger, C and Prabh, N and Witte, H and Roeseler, W and Riebesell, M and Sommer, RJ}, title = {DAF-19/RFX controls ciliogenesis and influences oxygen-induced social behaviors in Pristionchus pacificus.}, journal = {Evolution & development}, volume = {20}, number = {6}, pages = {233-243}, doi = {10.1111/ede.12271}, pmid = {30259625}, issn = {1525-142X}, mesh = {Animals ; Cilia/metabolism ; Oxygen/metabolism ; Regulatory Factor X1/*genetics/metabolism ; Rhabditida/classification/*cytology/*genetics/metabolism ; Social Behavior ; Transcription Factors/*genetics/metabolism ; }, abstract = {Cilia are complex organelles involved in sensory perception and motility with intraflagellar transport (IFT) proteins being essential for cilia assembly and function, but little is known about cilia in an evo-devo context. For example, recent comparisons revealed conservation and divergence of IFT components in the regulation of social feeding behaviors between the nematodes Caenorhabditis elegans and Pristionchus pacificus. Here, we focus on the P. pacificus RFX transcription factor daf-19, the master regulator of ciliogenesis in C. elegans. Two CRISPR/Cas9-induced Ppa-daf-19 mutants lack ciliary structures in amphid neurons and display chemosensory defects. In contrast to IFT mutants, Ppa-daf-19 mutants do not exhibit social behavior. However, they show weak locomotive responses to shifts in oxygen concentration, suggesting partial impairment in sensing or responding to oxygen. To identify targets of Ppa-daf-19 regulation we compared the transcriptomes of Ppa-daf-19 and wild-type animals and performed a bioinformatic search for the X-box RFX binding-site across the genome. The regulatory network of Ppa-DAF-19 involves IFT genes but also many taxonomically restricted genes. We identified a conserved X-box motif as the putative binding site, which was validated for the Ppa-dyf-1 gene. Thus, Ppa-DAF-19 controls ciliogenesis, influences oxygen-induced behaviors and displays a high turnover of its regulatory network.}, } @article {pmid30259619, year = {2018}, author = {Cerkvenik, U and Dodou, D and van Leeuwen, JL and Gussekloo, SWS}, title = {Functional principles of steerable multi-element probes in insects.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12467}, pmid = {30259619}, issn = {1469-185X}, support = {//NWO Domain Applied and Engineering Sciences (NWO TTW)/ ; }, abstract = {Hemipterans, mosquitoes, and parasitic wasps probe in a variety of substrates to find hosts for their larvae or food sources. Probes capable of sensing and precise steering enable insects to navigate through solid substrates without visual information and to reach targets that are hidden deep inside the substrate. The probes belong to non-related taxa and originate from abdominal structures (wasps) or mouthparts (hemipterans and mosquitoes), but nevertheless share several morphological characteristics. Although the transport function clearly differs (egg laying and acquisition of liquid food), the functional demands on the mechanical behaviour of the probe within the substrate tend to be similar. The probe needs to be thin to limit substrate deformation, and long, in order to attain substantial path lengths or depths. We linked the morphology across taxa to the different functional requirements, to provide insights into the biology of probing insects and the evolution of their probes. Current knowledge of insect probes is spread over many taxa, which offers the possibility to derive general characteristics of insect probing. Buckling during initial puncturing is limited by external support mechanisms. The probe itself consist of multiple (3-6) parts capable of sliding along one another. This multi-part construction presumably enables advancement and precise three-dimensional steering of the probe through the substrate with very low net external pushing forces, preventing buckling during substrate penetration. From a mechanical viewpoint, a minimum of three elements is required for 3D steering and volumetric exploration, as realised in the ovipositors of wasps. More elements, such as in six-element probes of mosquitoes, may enhance friction in soft substrates. Alternatively, additional elements can have functions other than 'drilling', such as saliva injection in mosquitoes. Despite the gross similarities, probes show differences in their cross sections, tip morphologies, relative lengths of their elements, and the shape of their interconnections. The hypothesis is that the probe morphology is influenced by the substrate properties, which are mostly unknown. Correlating the observed diversity to substrate-specific functional demands is therefore currently impossible. We conclude that a multipart probe with sliding elements is highly effective for volumetric substrate probing. Shared functional demands have led to an evolutionary convergence of slender multi-element probes in disparate insect taxa. To fully understand 3D probing, it is necessary to study the sensory and material properties, as well as the detailed kinematics and dynamics of the various probes in relation to the nature of the selective pressure originating from the species-specific substrates. Such knowledge will deepen our understanding of probing mechanisms and may support the development of slender, bio-inspired probes.}, } @article {pmid30259523, year = {2018}, author = {Tibbetts, EA and Pandit, S and Nondorf, D}, title = {Developmental plasticity and the origin of novel communication systems: Individual recognition in Polistes wasps.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2728-2735}, doi = {10.1111/evo.13613}, pmid = {30259523}, issn = {1558-5646}, support = {IOS-1557564//Division of Integrative Organismal Systems/ ; }, abstract = {Although developmental plasticity facilitates the evolutionary origin of many traits, the role of plasticity in the origin of novel communication systems has received little attention. If plasticity mediates the origin of new communication systems, exposure to a novel environment will induce new traits that could function as signals or receiver responses. Here, we test whether plasticity facilitates the origin of individual recognition. We reared a species of paper wasp that naturally lacks individual recognition (Polistes metricus) with a relative that has facial patterns that signal individual identity (Polistes fuscatus). We found P. metricus reared with individual identity signals learned unique wasp faces significantly more accurately than P. metricus reared without individual identity signals. However, exposure to individual identity signals was not sufficient to induce individual recognition in social contexts. These results suggest that if variable facial patterns arose in P. metricus, wasps would immediately improve their ability learn variable facial patterns, thereby facilitating the origin of individual face recognition. Improved learning is an initial step toward individual recognition that would need to be refined by selection to produce an established signaling system. Developmental plasticity may be an underappreciated factor facilitating the evolutionary origin of novel recognition systems.}, } @article {pmid30259522, year = {2018}, author = {Gamelon, M and Tufto, J and Nilsson, ALK and Jerstad, K and Røstad, OW and Stenseth, NC and Saether, BE}, title = {Environmental drivers of varying selective optima in a small passerine: A multivariate, multiepisodic approach.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2325-2342}, doi = {10.1111/evo.13610}, pmid = {30259522}, issn = {1558-5646}, support = {179569//Norges Forskningsråd/ ; 223257//Norges Forskningsråd/ ; }, abstract = {In changing environments, phenotypic traits are shaped by numerous agents of selection. The optimal phenotypic value maximizing the fitness of an individual thus varies through time and space with various environmental covariates. Selection may differ between different life-cycle stages and act on correlated traits inducing changes in the distribution of several traits simultaneously. Despite increasing interests in environmental sensitivity of phenotypic selection, estimating varying selective optima on various traits throughout the life cycle, while considering (a)biotic factors as potential selective agents has remained challenging. Here, we provide a statistical model to measure varying selective optima from longitudinal data. We apply our approach to analyze environmental sensitivity of phenotypic selection on egg-laying date and clutch size throughout the life cycle of a white-throated dipper population. We show the presence of a joint optimal phenotype that varies over the 35-year period, being dependent on altitude and temperature. We also find that optimal laying date is density-dependent, with high population density favoring earlier laying dates. By providing a flexible approach, widely applicable to free-ranging populations for which long-term data on individual phenotypes, fitness, and environmental factors are available, our study improves the understanding of phenotypic selection in varying environments.}, } @article {pmid30259084, year = {2018}, author = {Berrios, L and Ely, B}, title = {Achieving Accurate Sequence and Annotation Data for Caulobacter vibrioides CB13.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1642-1648}, pmid = {30259084}, issn = {1432-0991}, support = {R25 GM076277/GM/NIGMS NIH HHS/United States ; R25GM076277//National Institute of General Medical Sciences/ ; }, mesh = {Base Sequence/*genetics ; Caulobacter/*genetics ; Codon, Initiator/genetics ; Codon, Terminator/genetics ; Genome, Bacterial/*genetics ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Molecular Sequence Annotation/methods ; Open Reading Frames/genetics ; Pseudogenes/genetics ; }, abstract = {Annotated sequence data are instrumental in nearly all realms of biology. However, the advent of next-generation sequencing has rapidly facilitated an imbalance between accurate sequence data and accurate annotation data. To increase the annotation accuracy of the Caulobacter vibrioides CB13b1a (CB13) genome, we compared the PGAP and RAST annotations of the CB13 genome. A total of 64 unique genes were identified in the PGAP annotation that were either completely or partially absent in the RAST annotation, and a total of 16 genes were identified in the RAST annotation that were not included in the PGAP annotation. Moreover, PGAP identified 73 frameshifted genes and 22 genes with an internal stop. In contrast, RAST annotated the larger segment of these frameshifted genes without indicating a change in reading frame may have occurred. The RAST annotation did not include any genes with internal stop codons, since it chose start codons that were after the internal stop. To confirm the discrepancies between the two annotations and verify the accuracy of the CB13 genome sequence data, we re-sequenced and re-annotated the entire genome and obtained an identical sequence, except in a small number of homopolymer regions. A genome sequence comparison between the two versions allowed us to determine the correct number of bases in each homopolymer region, which eliminated frameshifts for 31 genes annotated as frameshifted genes and removed 24 pseudogenes from the PGAP annotation. Both annotation systems correctly identified genes that were missed by the other system. In addition, PGAP identified conserved gene fragments that represented the beginning of genes, but it employed no corrective method to adjust the reading frame of frameshifted genes or the start sites of genes harboring an internal stop codon. In doing so, the PGAP annotation identified a large number of pseudogenes, which may reflect evolutionary history but likely do not produce gene products. These results demonstrate that re-sequencing and annotation comparisons can be used to increase the accuracy of genomic data and the corresponding gene annotation.}, } @article {pmid30258232, year = {2018}, author = {Reimann, J and Schlauderer, S and Schmid, CP and Langer, F and Baierl, S and Kokh, KA and Tereshchenko, OE and Kimura, A and Lange, C and Güdde, J and Höfer, U and Huber, R}, title = {Subcycle observation of lightwave-driven Dirac currents in a topological surface band.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {396-400}, doi = {10.1038/s41586-018-0544-x}, pmid = {30258232}, issn = {1476-4687}, abstract = {Harnessing the carrier wave of light as an alternating-current bias may enable electronics at optical clock rates1. Lightwave-driven currents have been assumed to be essential for high-harmonic generation in solids2-6, charge transport in nanostructures7,8, attosecond-streaking experiments9-16 and atomic-resolution ultrafast microscopy17,18. However, in conventional semiconductors and dielectrics, the finite effective mass and ultrafast scattering of electrons limit their ballistic excursion and velocity. The Dirac-like, quasi-relativistic band structure of topological insulators19-29 may allow these constraints to be lifted and may thus open a new era of lightwave electronics. To understand the associated, complex motion of electrons, comprehensive experimental access to carrier-wave-driven currents is crucial. Here we report angle-resolved photoemission spectroscopy with subcycle time resolution that enables us to observe directly how the carrier wave of a terahertz light pulse accelerates Dirac fermions in the band structure of the topological surface state of Bi2Te3. While terahertz streaking of photoemitted electrons traces the electromagnetic field at the surface, the acceleration of Dirac states leads to a strong redistribution of electrons in momentum space. The inertia-free surface currents are protected by spin-momentum locking and reach peak densities as large as two amps per centimetre, with ballistic mean free paths of several hundreds of nanometres, opening up a realistic parameter space for all-coherent lightwave-driven electronic devices. Furthermore, our subcycle-resolution analysis of the band structure may greatly improve our understanding of electron dynamics and strong-field interaction in solids.}, } @article {pmid30258231, year = {2018}, author = {Plein, A and Fantin, A and Denti, L and Pollard, JW and Ruhrberg, C}, title = {Erythro-myeloid progenitors contribute endothelial cells to blood vessels.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {223-228}, pmid = {30258231}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; 095623/Z/11/Z//Wellcome Trust/United Kingdom ; MR/N011511/1//Medical Research Council/United Kingdom ; }, abstract = {The earliest blood vessels in mammalian embryos are formed when endothelial cells differentiate from angioblasts and coalesce into tubular networks. Thereafter, the endothelium is thought to expand solely by proliferation of pre-existing endothelial cells. Here we show that a complementary source of endothelial cells is recruited into pre-existing vasculature after differentiation from the earliest precursors of erythrocytes, megakaryocytes and macrophages, the erythro-myeloid progenitors (EMPs) that are born in the yolk sac. A first wave of EMPs contributes endothelial cells to the yolk sac endothelium, and a second wave of EMPs colonizes the embryo and contributes endothelial cells to intraembryonic endothelium in multiple organs, where they persist into adulthood. By demonstrating that EMPs constitute a hitherto unrecognized source of endothelial cells, we reveal that embryonic blood vascular endothelium expands in a dual mechanism that involves both the proliferation of pre-existing endothelial cells and the incorporation of endothelial cells derived from haematopoietic precursors.}, } @article {pmid30258230, year = {2018}, author = {Dennis, EJ and Dobosiewicz, M and Jin, X and Duvall, LB and Hartman, PS and Bargmann, CI and Vosshall, LB}, title = {A natural variant and engineered mutation in a GPCR promote DEET resistance in C. elegans.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {119-123}, doi = {10.1038/s41586-018-0546-8}, pmid = {30258230}, issn = {1476-4687}, abstract = {DEET (N,N-diethyl-meta-toluamide) is a synthetic chemical identified by the US Department of Agriculture in 1946 in a screen for repellents to protect soldiers from mosquito-borne diseases1,2. Since its discovery, DEET has become the world's most widely used arthropod repellent and is effective against invertebrates separated by millions of years of evolution-including biting flies3, honeybees4, ticks5, and land leeches3. In insects, DEET acts on the olfactory system5-12 and requires the olfactory receptor co-receptor Orco7,9-12, but exactly how it works remains controversial13. Here we show that the nematode Caenorhabditis elegans is sensitive to DEET and use this genetically tractable animal to study the mechanism of action of this chemical. We found that DEET is not a volatile repellent, but instead interferes selectively with chemotaxis to a variety of attractant and repellent molecules. In a forward genetic screen for DEET-resistant worms, we identified a gene that encodes a single G protein-coupled receptor, str-217, which is expressed in a single pair of chemosensory neurons that are responsive to DEET, called ADL neurons. Mis-expression of str-217 in another chemosensory neuron conferred responses to DEET. Engineered str-217 mutants, and a wild isolate of C. elegans that carries a str-217 deletion, are resistant to DEET. We found that DEET can interfere with behaviour by inducing an increase in average pause length during locomotion, and show that this increase in pausing requires both str-217 and ADL neurons. Finally, we demonstrated that ADL neurons are activated by DEET and that optogenetic activation of ADL neurons increased average pause length. This is consistent with the 'confusant' hypothesis, which proposes that DEET is not a simple repellent but that it instead modulates multiple olfactory pathways to scramble behavioural responses10,11. Our results suggest a consistent motif in the effectiveness of DEET across widely divergent taxa: an effect on multiple chemosensory neurons that disrupts the pairing between odorant stimulus and behavioural response.}, } @article {pmid30258229, year = {2018}, author = {Bjorkman, AD and Myers-Smith, IH and Elmendorf, SC and Normand, S and Rüger, N and Beck, PSA and Blach-Overgaard, A and Blok, D and Cornelissen, JHC and Forbes, BC and Georges, D and Goetz, SJ and Guay, KC and Henry, GHR and HilleRisLambers, J and Hollister, RD and Karger, DN and Kattge, J and Manning, P and Prevéy, JS and Rixen, C and Schaepman-Strub, G and Thomas, HJD and Vellend, M and Wilmking, M and Wipf, S and Carbognani, M and Hermanutz, L and Lévesque, E and Molau, U and Petraglia, A and Soudzilovskaia, NA and Spasojevic, MJ and Tomaselli, M and Vowles, T and Alatalo, JM and Alexander, HD and Anadon-Rosell, A and Angers-Blondin, S and Beest, MT and Berner, L and Björk, RG and Buchwal, A and Buras, A and Christie, K and Cooper, EJ and Dullinger, S and Elberling, B and Eskelinen, A and Frei, ER and Grau, O and Grogan, P and Hallinger, M and Harper, KA and Heijmans, MMPD and Hudson, J and Hülber, K and Iturrate-Garcia, M and Iversen, CM and Jaroszynska, F and Johnstone, JF and Jørgensen, RH and Kaarlejärvi, E and Klady, R and Kuleza, S and Kulonen, A and Lamarque, LJ and Lantz, T and Little, CJ and Speed, JDM and Michelsen, A and Milbau, A and Nabe-Nielsen, J and Nielsen, SS and Ninot, JM and Oberbauer, SF and Olofsson, J and Onipchenko, VG and Rumpf, SB and Semenchuk, P and Shetti, R and Collier, LS and Street, LE and Suding, KN and Tape, KD and Trant, A and Treier, UA and Tremblay, JP and Tremblay, M and Venn, S and Weijers, S and Zamin, T and Boulanger-Lapointe, N and Gould, WA and Hik, DS and Hofgaard, A and Jónsdóttir, IS and Jorgenson, J and Klein, J and Magnusson, B and Tweedie, C and Wookey, PA and Bahn, M and Blonder, B and van Bodegom, PM and Bond-Lamberty, B and Campetella, G and Cerabolini, BEL and Chapin, FS and Cornwell, WK and Craine, J and Dainese, M and de Vries, FT and Díaz, S and Enquist, BJ and Green, W and Milla, R and Niinemets, Ü and Onoda, Y and Ordoñez, JC and Ozinga, WA and Penuelas, J and Poorter, H and Poschlod, P and Reich, PB and Sandel, B and Schamp, B and Sheremetev, S and Weiher, E}, title = {Plant functional trait change across a warming tundra biome.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {57-62}, doi = {10.1038/s41586-018-0563-7}, pmid = {30258229}, issn = {1476-4687}, abstract = {The tundra is warming more rapidly than any other biome on Earth, and the potential ramifications are far-reaching because of global feedback effects between vegetation and climate. A better understanding of how environmental factors shape plant structure and function is crucial for predicting the consequences of environmental change for ecosystem functioning. Here we explore the biome-wide relationships between temperature, moisture and seven key plant functional traits both across space and over three decades of warming at 117 tundra locations. Spatial temperature-trait relationships were generally strong but soil moisture had a marked influence on the strength and direction of these relationships, highlighting the potentially important influence of changes in water availability on future trait shifts in tundra plant communities. Community height increased with warming across all sites over the past three decades, but other traits lagged far behind predicted rates of change. Our findings highlight the challenge of using space-for-time substitution to predict the functional consequences of future warming and suggest that functions that are tied closely to plant height will experience the most rapid change. They also reveal the strength with which environmental factors shape biotic communities at the coldest extremes of the planet and will help to improve projections of functional changes in tundra ecosystems with climate warming.}, } @article {pmid30258228, year = {2018}, author = {Niemi, MEK and Martin, HC and Rice, DL and Gallone, G and Gordon, S and Kelemen, M and McAloney, K and McRae, J and Radford, EJ and Yu, S and Gecz, J and Martin, NG and Wright, CF and Fitzpatrick, DR and Firth, HV and Hurles, ME and Barrett, JC}, title = {Common genetic variants contribute to risk of rare severe neurodevelopmental disorders.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {268-271}, doi = {10.1038/s41586-018-0566-4}, pmid = {30258228}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {There are thousands of rare human disorders that are caused by single deleterious, protein-coding genetic variants1. However, patients with the same genetic defect can have different clinical presentations2-4, and some individuals who carry known disease-causing variants can appear unaffected5. Here, to understand what explains these differences, we study a cohort of 6,987 children assessed by clinical geneticists to have severe neurodevelopmental disorders such as global developmental delay and autism, often in combination with abnormalities of other organ systems. Although the genetic causes of these neurodevelopmental disorders are expected to be almost entirely monogenic, we show that 7.7% of variance in risk is attributable to inherited common genetic variation. We replicated this genome-wide common variant burden by showing, in an independent sample of 728 trios (comprising a child plus both parents) from the same cohort, that this burden is over-transmitted from parents to children with neurodevelopmental disorders. Our common-variant signal is significantly positively correlated with genetic predisposition to lower educational attainment, decreased intelligence and risk of schizophrenia. We found that common-variant risk was not significantly different between individuals with and without a known protein-coding diagnostic variant, which suggests that common-variant risk affects patients both with and without a monogenic diagnosis. In addition, previously published common-variant scores for autism, height, birth weight and intracranial volume were all correlated with these traits within our cohort, which suggests that phenotypic expression in individuals with monogenic disorders is affected by the same variants as in the general population. Our results demonstrate that common genetic variation affects both overall risk and clinical presentation in neurodevelopmental disorders that are typically considered to be monogenic.}, } @article {pmid30258227, year = {2018}, author = {Lorenz, L and Axnick, J and Buschmann, T and Henning, C and Urner, S and Fang, S and Nurmi, H and Eichhorst, N and Holtmeier, R and Bódis, K and Hwang, JH and Müssig, K and Eberhard, D and Stypmann, J and Kuss, O and Roden, M and Alitalo, K and Häussinger, D and Lammert, E}, title = {Mechanosensing by β1 integrin induces angiocrine signals for liver growth and survival.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {128-132}, doi = {10.1038/s41586-018-0522-3}, pmid = {30258227}, issn = {1476-4687}, abstract = {Angiocrine signals derived from endothelial cells are an important component of intercellular communication and have a key role in organ growth, regeneration and disease1-4. These signals have been identified and studied in multiple organs, including the liver, pancreas, lung, heart, bone, bone marrow, central nervous system, retina and some cancers1-4. Here we use the developing liver as a model organ to study angiocrine signals5,6, and show that the growth rate of the liver correlates both spatially and temporally with blood perfusion to this organ. By manipulating blood flow through the liver vasculature, we demonstrate that vessel perfusion activates β1 integrin and vascular endothelial growth factor receptor 3 (VEGFR3). Notably, both β1 integrin and VEGFR3 are strictly required for normal production of hepatocyte growth factor, survival of hepatocytes and liver growth. Ex vivo perfusion of adult mouse liver and in vitro mechanical stretching of human hepatic endothelial cells illustrate that mechanotransduction alone is sufficient to turn on angiocrine signals. When the endothelial cells are mechanically stretched, angiocrine signals trigger in vitro proliferation and survival of primary human hepatocytes. Our findings uncover a signalling pathway in vascular endothelial cells that translates blood perfusion and mechanotransduction into organ growth and maintenance.}, } @article {pmid30258226, year = {2018}, author = {van den Eijnden, J and Degenaar, N and Russell, TD and Wijnands, R and Miller-Jones, JCA and Sivakoff, GR and Hernández Santisteban, JV}, title = {An evolving jet from a strongly magnetized accreting X-ray pulsar.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {233-235}, doi = {10.1038/s41586-018-0524-1}, pmid = {30258226}, issn = {1476-4687}, abstract = {Relativistic jets are observed throughout the Universe and strongly affect their surrounding environments on a range of physical scales, from Galactic binary systems1 to galaxies and clusters of galaxies2. All types of accreting black hole and neutron star have been observed to launch jets3, with the exception of neutron stars with strong magnetic fields4,5 (higher than 1012 gauss), leading to the conclusion that their magnetic field strength inhibits jet formation6. However, radio emission recently detected from two such objects could have a jet origin, among other possible explanations7,8, indicating that this long-standing idea might need to be reconsidered. But definitive observational evidence of such jets is still lacking. Here we report observations of an evolving jet launched by a strongly magnetized neutron star accreting above the theoretical maximum rate given by the Eddington limit. The radio luminosity of the jet is two orders of magnitude fainter than those seen in other neutron stars with similar X-ray luminosities9, implying an important role for the properties of the neutron star in regulating jet power. Our result also shows that the strong magnetic fields of ultra-luminous X-ray pulsars do not prevent such sources from launching jets.}, } @article {pmid30258225, year = {2018}, author = {Lai, B and Gao, W and Cui, K and Xie, W and Tang, Q and Jin, W and Hu, G and Ni, B and Zhao, K}, title = {Principles of nucleosome organization revealed by single-cell micrococcal nuclease sequencing.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {281-285}, doi = {10.1038/s41586-018-0567-3}, pmid = {30258225}, issn = {1476-4687}, support = {/HL/NHLBI NIH HHS/United States ; }, abstract = {Nucleosome positioning is critical to chromatin accessibility and is associated with gene expression programs in cells1-3. Previous nucleosome mapping methods assemble profiles from cell populations and reveal a cell-averaged pattern: nucleosomes are positioned and form a phased array that surrounds the transcription start sites of active genes3-6 and DNase I hypersensitive sites7. However, even in a homogenous population of cells, cells exhibit heterogeneity in expression in response to active signalling8,9 that may be related to heterogeneity in chromatin accessibility10-12. Here we report a technique, termed single-cell micrococcal nuclease sequencing (scMNase-seq), that can be used to simultaneously measure genome-wide nucleosome positioning and chromatin accessibility in single cells. Application of scMNase-seq to NIH3T3 cells, mouse primary naive CD4 T cells and mouse embryonic stem cells reveals two principles of nucleosome organization: first, nucleosomes in heterochromatin regions, or that surround the transcription start sites of silent genes, show large variation in positioning across different cells but are highly uniformly spaced along the nucleosome array; and second, nucleosomes that surround the transcription start sites of active genes and DNase I hypersensitive sites show little variation in positioning across different cells but are relatively heterogeneously spaced along the nucleosome array. We found a bimodal distribution of nucleosome spacing at DNase I hypersensitive sites, which corresponds to inaccessible and accessible states and is associated with nucleosome variation and variation in accessibility across cells. Nucleosome variation is smaller within single cells than across cells, and smaller within the same cell type than across cell types. A large fraction of naive CD4 T cells and mouse embryonic stem cells shows depleted nucleosome occupancy at the de novo enhancers detected in their respective differentiated lineages, revealing the existence of cells primed for differentiation to specific lineages in undifferentiated cell populations.}, } @article {pmid30258166, year = {2018}, author = {}, title = {Gravity glitch, biodefence plan and an asteroid first.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {438-439}, doi = {10.1038/d41586-018-06780-9}, pmid = {30258166}, issn = {1476-4687}, } @article {pmid30258165, year = {2018}, author = {Masood, E and Vesper, I and Van Noorden, R}, title = {Six months to Brexit: how scientists are preparing for the split.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {452-454}, doi = {10.1038/d41586-018-06781-8}, pmid = {30258165}, issn = {1476-4687}, } @article {pmid30258164, year = {2018}, author = {Willyard, C}, title = {The innovative therapies that could break the brain-cancer stalemate.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S59-S61}, doi = {10.1038/d41586-018-06713-6}, pmid = {30258164}, issn = {1476-4687}, } @article {pmid30258163, year = {2018}, author = {Savage, N}, title = {Searching for the roots of brain cancer.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S50-S51}, doi = {10.1038/d41586-018-06709-2}, pmid = {30258163}, issn = {1476-4687}, } @article {pmid30258162, year = {2018}, author = {Arney, K}, title = {Improving brain-cancer therapies through mathematical modelling.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S52-S53}, doi = {10.1038/d41586-018-06710-9}, pmid = {30258162}, issn = {1476-4687}, } @article {pmid30258161, year = {2018}, author = {DeWeerdt, S}, title = {The genomics of brain cancer.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S54-S55}, doi = {10.1038/d41586-018-06711-8}, pmid = {30258161}, issn = {1476-4687}, } @article {pmid30258160, year = {2018}, author = {Drew, L}, title = {The unexpected role of histones in childhood brain cancer.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S56-S58}, doi = {10.1038/d41586-018-06712-7}, pmid = {30258160}, issn = {1476-4687}, } @article {pmid30258159, year = {2018}, author = {Armstrong, T}, title = {See brain cancer as more than just the sum of biology.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S45}, doi = {10.1038/d41586-018-06706-5}, pmid = {30258159}, issn = {1476-4687}, } @article {pmid30258158, year = {2018}, author = {Nowogrodzki, A}, title = {How cerebral organoids are guiding brain-cancer research and therapies.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S48-S49}, doi = {10.1038/d41586-018-06708-3}, pmid = {30258158}, issn = {1476-4687}, } @article {pmid30258157, year = {2018}, author = {Bender, E}, title = {Getting cancer drugs into the brain.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S46-S47}, doi = {10.1038/d41586-018-06707-4}, pmid = {30258157}, issn = {1476-4687}, } @article {pmid30258156, year = {2018}, author = {Gould, J}, title = {Breaking down the epidemiology of brain cancer.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S40-S41}, doi = {10.1038/d41586-018-06704-7}, pmid = {30258156}, issn = {1476-4687}, } @article {pmid30258155, year = {2018}, author = {Eisenstein, M}, title = {Immunotherapy offers a promising bet against brain cancer.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S42-S44}, doi = {10.1038/d41586-018-06705-6}, pmid = {30258155}, issn = {1476-4687}, } @article {pmid30258154, year = {2018}, author = {Brody, H}, title = {Brain cancer.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {S39}, doi = {10.1038/d41586-018-06703-8}, pmid = {30258154}, issn = {1476-4687}, } @article {pmid30258152, year = {2018}, author = {Chang, AJ and Kim, NS and Hireed, H and de Arce, AD and Ortega, FE and Riegler, J and Madison, DV and Krasnow, MA}, title = {Chang et al. reply.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {E41}, doi = {10.1038/s41586-018-0547-7}, pmid = {30258152}, issn = {1476-4687}, } @article {pmid30258151, year = {2018}, author = {Torres-Torrelo, H and Ortega-Sáenz, P and Macías, D and Omura, M and Zhou, T and Matsunami, H and Johnson, RS and Mombaerts, P and López-Barneo, J}, title = {The role of Olfr78 in the breathing circuit of mice.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {E33-E40}, doi = {10.1038/s41586-018-0545-9}, pmid = {30258151}, issn = {1476-4687}, } @article {pmid30258150, year = {2018}, author = {Sipp, D and Robey, PG and Turner, L}, title = {Clear up this stem-cell mess.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {455-457}, doi = {10.1038/d41586-018-06756-9}, pmid = {30258150}, issn = {1476-4687}, } @article {pmid30258149, year = {2018}, author = {Cyranoski, D}, title = {Why Chinese medicine is heading for clinics around the world.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {448-450}, doi = {10.1038/d41586-018-06782-7}, pmid = {30258149}, issn = {1476-4687}, } @article {pmid30258148, year = {2018}, author = {Scott, GR}, title = {Last contact.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {574}, doi = {10.1038/d41586-018-06795-2}, pmid = {30258148}, issn = {1476-4687}, } @article {pmid30258147, year = {2018}, author = {Haigwood, NL}, title = {Antibodies pose a double threat to HIV.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {468-470}, doi = {10.1038/d41586-018-06773-8}, pmid = {30258147}, issn = {1476-4687}, support = {P51 OD011092/OD/NIH HHS/United States ; }, mesh = {Combined Modality Therapy ; *HIV Antibodies ; *HIV-1 ; }, } @article {pmid30258146, year = {2018}, author = {Praetorius, S}, title = {The price of grief.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {571}, doi = {10.1038/d41586-018-06793-4}, pmid = {30258146}, issn = {1476-4687}, } @article {pmid30258145, year = {2018}, author = {Woolston, C}, title = {The quest for postdoctoral independence.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {569-571}, doi = {10.1038/d41586-018-06794-3}, pmid = {30258145}, issn = {1476-4687}, } @article {pmid30258144, year = {2018}, author = {Zhang, S and Cicoira, F}, title = {Flexible self-powered biosensors.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {466-467}, doi = {10.1038/d41586-018-06788-1}, pmid = {30258144}, issn = {1476-4687}, mesh = {*Biosensing Techniques ; *Electronics ; }, } @article {pmid30258143, year = {2018}, author = {Howell, LL}, title = {Complex mechanical motion guided without external control.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {470-471}, doi = {10.1038/d41586-018-06787-2}, pmid = {30258143}, issn = {1476-4687}, } @article {pmid30258142, year = {2018}, author = {Catzeflis, FM}, title = {Mega mining project in French Guiana threatens Amazonian biodiversity.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {464}, doi = {10.1038/d41586-018-06803-5}, pmid = {30258142}, issn = {1476-4687}, } @article {pmid30258141, year = {2018}, author = {Carbone, M}, title = {Just a handful of publications can collect the prize.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {464}, doi = {10.1038/d41586-018-06816-0}, pmid = {30258141}, issn = {1476-4687}, } @article {pmid30258140, year = {2018}, author = {Ewers, RM}, title = {Do boring speakers really talk for longer?.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {464}, doi = {10.1038/d41586-018-06817-z}, pmid = {30258140}, issn = {1476-4687}, } @article {pmid30258139, year = {2018}, author = {Baru, C}, title = {How to deliver translational data-science benefits to science and society.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {464}, doi = {10.1038/d41586-018-06804-4}, pmid = {30258139}, issn = {1476-4687}, } @article {pmid30258138, year = {2018}, author = {Coulais, C and Sabbadini, A and Vink, F and van Hecke, M}, title = {Multi-step self-guided pathways for shape-changing metamaterials.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {512-515}, doi = {10.1038/s41586-018-0541-0}, pmid = {30258138}, issn = {1476-4687}, abstract = {Multi-step pathways-which consist of a sequence of reconfigurations of a structure-are central to the functionality of various natural and artificial systems. Such pathways execute autonomously in self-guided processes such as protein folding1 and self-assembly2-5, but have previously required external control to execute in macroscale mechanical systems, provided by, for example, actuators in robotics6-9 or manual folding in origami8,10-12. Here we demonstrate shape-changing, macroscale mechanical metamaterials that undergo self-guided, multi-step reconfiguration in response to global uniform compression. We avoid the need for external control by using metamaterials that are made purely of passive components. The design of the metamaterials combines nonlinear mechanical elements with a multimodal architecture that enables a sequence of topological reconfigurations caused by the formation of internal self-contacts between the elements of the metamaterial. We realize the metamaterials by using computer-controlled water-jet cutting of flexible materials, and show that the multi-step pathway and final configuration can be controlled by rational design of the nonlinear mechanical elements. We also demonstrate that the self-contacts suppress errors in the pathway. Finally, we create hierarchical architectures to extend the number of distinct reconfiguration steps. Our work establishes general principles for designing mechanical pathways, opening up new avenues for self-folding media11,12, pluripotent materials9,13 and pliable devices14 in areas such as stretchable electronics and soft robotics15.}, } @article {pmid30258137, year = {2018}, author = {Park, S and Heo, SW and Lee, W and Inoue, D and Jiang, Z and Yu, K and Jinno, H and Hashizume, D and Sekino, M and Yokota, T and Fukuda, K and Tajima, K and Someya, T}, title = {Self-powered ultra-flexible electronics via nano-grating-patterned organic photovoltaics.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {516-521}, doi = {10.1038/s41586-018-0536-x}, pmid = {30258137}, issn = {1476-4687}, abstract = {Next-generation biomedical devices1-9 will need to be self-powered and conformable to human skin or other tissue. Such devices would enable the accurate and continuous detection of physiological signals without the need for an external power supply or bulky connecting wires. Self-powering functionality could be provided by flexible photovoltaics that can adhere to moveable and complex three-dimensional biological tissues1-4 and skin5-9. Ultra-flexible organic power sources10-13 that can be wrapped around an object have proven mechanical and thermal stability in long-term operation13, making them potentially useful in human-compatible electronics. However, the integration of these power sources with functional electric devices including sensors has not yet been demonstrated because of their unstable output power under mechanical deformation and angular change. Also, it will be necessary to minimize high-temperature and energy-intensive processes10,12 when fabricating an integrated power source and sensor, because such processes can damage the active material of the functional device and deform the few-micrometre-thick polymeric substrates. Here we realize self-powered ultra-flexible electronic devices that can measure biometric signals with very high signal-to-noise ratios when applied to skin or other tissue. We integrated organic electrochemical transistors used as sensors with organic photovoltaic power sources on a one-micrometre-thick ultra-flexible substrate. A high-throughput room-temperature moulding process was used to form nano-grating morphologies (with a periodicity of 760 nanometres) on the charge transporting layers. This substantially increased the efficiency of the organophotovoltaics, giving a high power-conversion efficiency that reached 10.5 per cent and resulted in a high power-per-weight value of 11.46 watts per gram. The organic electrochemical transistors exhibited a transconductance of 0.8 millisiemens and fast responsivity above one kilohertz under physiological conditions, which resulted in a maximum signal-to-noise ratio of 40.02 decibels for cardiac signal detection. Our findings offer a general platform for next-generation self-powered electronics.}, } @article {pmid30258136, year = {2018}, author = {Mendoza, P and Gruell, H and Nogueira, L and Pai, JA and Butler, AL and Millard, K and Lehmann, C and Suárez, I and Oliveira, TY and Lorenzi, JCC and Cohen, YZ and Wyen, C and Kümmerle, T and Karagounis, T and Lu, CL and Handl, L and Unson-O'Brien, C and Patel, R and Ruping, C and Schlotz, M and Witmer-Pack, M and Shimeliovich, I and Kremer, G and Thomas, E and Seaton, KE and Horowitz, J and West, AP and Bjorkman, PJ and Tomaras, GD and Gulick, RM and Pfeifer, N and Fätkenheuer, G and Seaman, MS and Klein, F and Caskey, M and Nussenzweig, MC}, title = {Combination therapy with anti-HIV-1 antibodies maintains viral suppression.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {479-484}, pmid = {30258136}, issn = {1476-4687}, support = {UM1 AI126620/AI/NIAID NIH HHS/United States ; UM1 AI100663/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 AI129795/AI/NIAID NIH HHS/United States ; P30 AI124414/AI/NIAID NIH HHS/United States ; }, abstract = {Individuals infected with HIV-1 require lifelong antiretroviral therapy, because interruption of treatment leads to rapid rebound viraemia. Here we report on a phase 1b clinical trial in which a combination of 3BNC117 and 10-1074, two potent monoclonal anti-HIV-1 broadly neutralizing antibodies that target independent sites on the HIV-1 envelope spike, was administered during analytical treatment interruption. Participants received three infusions of 30 mg kg-1 of each antibody at 0, 3 and 6 weeks. Infusions of the two antibodies were generally well-tolerated. The nine enrolled individuals with antibody-sensitive latent viral reservoirs maintained suppression for between 15 and more than 30 weeks (median of 21 weeks), and none developed viruses that were resistant to both antibodies. We conclude that the combination of the anti-HIV-1 monoclonal antibodies 3BNC117 and 10-1074 can maintain long-term suppression in the absence of antiretroviral therapy in individuals with antibody-sensitive viral reservoirs.}, } @article {pmid30258135, year = {2018}, author = {Trowbridge, A and Reich, D and Gaunt, MJ}, title = {Multicomponent synthesis of tertiary alkylamines by photocatalytic olefin-hydroaminoalkylation.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {522-527}, doi = {10.1038/s41586-018-0537-9}, pmid = {30258135}, issn = {1476-4687}, abstract = {There is evidence to suggest that increasing the level of saturation (that is, the number of sp3-hybridized carbon atoms) of small molecules can increase their likelihood of success in the drug discovery pipeline1. Owing to their favourable physical properties, alkylamines have become ubiquitous among pharmaceutical agents, small-molecule biological probes and pre-clinical candidates2. Despite their importance, the synthesis of amines is still dominated by two methods: N-alkylation and carbonyl reductive amination3. Therefore, the increasing demand for saturated polar molecules in drug discovery has continued to drive the development of practical catalytic methods for the synthesis of complex alkylamines4-7. In particular, processes that transform accessible feedstocks into sp3-rich architectures provide a strategic advantage in the synthesis of complex alkylamines. Here we report a multicomponent, reductive photocatalytic technology that combines readily available dialkylamines, carbonyls and alkenes to build architecturally complex and functionally diverse tertiary alkylamines in a single step. This olefin-hydroaminoalkylation process involves a visible-light-mediated reduction of in-situ-generated iminium ions to selectively furnish previously inaccessible alkyl-substituted α-amino radicals, which subsequently react with alkenes to form C(sp3)-C(sp3) bonds. The operationally straightforward reaction exhibits broad functional-group tolerance, facilitates the synthesis of drug-like amines that are not readily accessible by other methods and is amenable to late-stage functionalization applications, making it of interest in areas such as pharmaceutical and agrochemical research.}, } @article {pmid30258134, year = {2018}, author = {Jiang, YF and Cantiello, M and Bildsten, L and Quataert, E and Blaes, O and Stone, J}, title = {Outbursts of luminous blue variable stars from variations in the helium opacity.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {498-501}, doi = {10.1038/s41586-018-0525-0}, pmid = {30258134}, issn = {1476-4687}, abstract = {Luminous blue variables are massive, evolved stars that exhibit large variations in luminosity and size on timescales from months to years, with high associated rates of mass loss1-5. In addition to this on-going variability, these stars exhibit outburst phases, during which their size increases and as a result their effective temperature decreases, typically to about 9,000 kelvin3,6. Outbursts are believed to be caused by the radiation force on the cooler, more opaque, outer layers of the star balancing or even exceeding the force of gravity, although the exact mechanisms are unknown and cannot be determined using one-dimensional, spherically symmetric models of stars because such models cannot determine the physical processes that occur in this regime7. Here we report three-dimensional simulations of massive, radiation-dominated stars, which show that helium opacity has an important role in triggering outbursts and setting the observed effective temperature during outbursts of about 9,000 kelvin. It probably also triggers the episodic mass loss at rates of 10-7 to 10-5 solar masses per year. The peak in helium opacity is evident in our three-dimensional simulations only because the density and temperature of the stellar envelope (the outer part of the star near the photosphere) need to be determined self-consistently with convection, which cannot be done in one-dimensional models that assume spherical symmetry. The simulations reproduce observations of long-timescale variability, and predict that convection causes irregular oscillations in the radii of the stars and variations in brightness of 10-30 per cent on a typical timescale of a few days. The amplitudes of these short-timescale variations are predicted to be even larger for cooler stars (in the outburst phase). This short-timescale variability should be observable with high-cadence observations.}, } @article {pmid30258110, year = {2018}, author = {Poynder, R}, title = {Open access - the movie.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {37-38}, doi = {10.1038/d41586-018-06140-7}, pmid = {30258110}, issn = {1476-4687}, } @article {pmid30257950, year = {2018}, author = {Yeon, JH and Park, CG and Hille, B and Suh, BC}, title = {Translocatable voltage-gated Ca2+ channel β subunits in α1-β complexes reveal competitive replacement yet no spontaneous dissociation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9934-E9943}, pmid = {30257950}, issn = {1091-6490}, support = {R37 NS008174/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Binding, Competitive ; Calcium Channels, L-Type/*metabolism ; Calcium Channels, N-Type/*metabolism ; Cytosol/metabolism ; Endoplasmic Reticulum/metabolism ; Ion Channel Gating/*physiology ; Mitochondria/metabolism ; Phosphatidylinositols/*metabolism ; Protein Isoforms ; Protein Subunits ; Protein Transport ; Rats ; Sirolimus/*metabolism ; }, abstract = {β subunits of high voltage-gated Ca2+ (CaV) channels promote cell-surface expression of pore-forming α1 subunits and regulate channel gating through binding to the α-interaction domain (AID) in the first intracellular loop. We addressed the stability of CaV α1B-β interactions by rapamycin-translocatable CaV β subunits that allow drug-induced sequestration and uncoupling of the β subunit from CaV2.2 channel complexes in intact cells. Without CaV α1B/α2δ1, all modified β subunits, except membrane-tethered β2a and β2e, are in the cytosol and rapidly translocate upon rapamycin addition to anchors on target organelles: plasma membrane, mitochondria, or endoplasmic reticulum. In cells coexpressing CaV α1B/α2δ1 subunits, the translocatable β subunits colocalize at the plasma membrane with α1B and stay there after rapamycin application, indicating that interactions between α1B and bound β subunits are very stable. However, the interaction becomes dynamic when other competing β isoforms are coexpressed. Addition of rapamycin, then, switches channel gating and regulation by phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] lipid. Thus, expression of free β isoforms around the channel reveals a dynamic aspect to the α1B-β interaction. On the other hand, translocatable β subunits with AID-binding site mutations are easily dissociated from CaV α1B on the addition of rapamycin, decreasing current amplitude and PI(4,5)P2 sensitivity. Furthermore, the mutations slow CaV2.2 current inactivation and shift the voltage dependence of activation to more positive potentials. Mutated translocatable β subunits work similarly in CaV2.3 channels. In sum, the strong interaction of CaV α1B-β subunits can be overcome by other free β isoforms, permitting dynamic changes in channel properties in intact cells.}, } @article {pmid30257949, year = {2018}, author = {Andreani, V and Ramamoorthy, S and Pandey, A and Lupar, E and Nutt, SL and Lämmermann, T and Grosschedl, R}, title = {Cochaperone Mzb1 is a key effector of Blimp1 in plasma cell differentiation and β1-integrin function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9630-E9639}, pmid = {30257949}, issn = {1091-6490}, mesh = {Animals ; Bone Marrow Cells/cytology/*metabolism ; Cell Differentiation/*physiology ; Immunoglobulin M/genetics/metabolism ; Integrin beta1/genetics/*metabolism ; Mice ; Mice, Knockout ; Molecular Chaperones/genetics/*metabolism ; Plasma Cells/cytology/*metabolism ; Positive Regulatory Domain I-Binding Factor 1/genetics/*metabolism ; }, abstract = {Plasma cell differentiation involves coordinated changes in gene expression and functional properties of B cells. Here, we study the role of Mzb1, a Grp94 cochaperone that is expressed in marginal zone (MZ) B cells and during the terminal differentiation of B cells to antibody-secreting cells. By analyzing Mzb1-/- Prdm1+/gfp mice, we find that Mzb1 is specifically required for the differentiation and function of antibody-secreting cells in a T cell-independent immune response. We find that Mzb1-deficiency mimics, in part, the phenotype of Blimp1 deficiency, including the impaired secretion of IgM and the deregulation of Blimp1 target genes. In addition, we find that Mzb1-/- plasmablasts show a reduced activation of β1-integrin, which contributes to the impaired plasmablast differentiation and migration of antibody-secreting cells to the bone marrow. Thus, Mzb1 function is required for multiple aspects of plasma cell differentiation.}, } @article {pmid30257948, year = {2018}, author = {Chernov, MM and Friedman, RM and Chen, G and Stoner, GR and Roe, AW}, title = {Functionally specific optogenetic modulation in primate visual cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10505-10510}, pmid = {30257948}, issn = {1091-6490}, support = {R21 AA020515/AA/NIAAA NIH HHS/United States ; R21 EY022853/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Channelrhodopsins/*genetics ; Haplorhini ; Neurons/cytology/*physiology ; *Optogenetics ; *Photic Stimulation ; Vision, Ocular/*physiology ; Visual Cortex/*physiology ; Visual Perception/*physiology ; }, abstract = {In primates, visual perception is mediated by brain circuits composed of submillimeter nodes linked together in specific networks that process different types of information, such as eye specificity and contour orientation. We hypothesized that optogenetic stimulation targeted to cortical nodes could selectively activate such cortical networks. We used viral transfection methods to confer light sensitivity to neurons in monkey primary visual cortex. Using intrinsic signal optical imaging and single-unit electrophysiology to assess effects of targeted optogenetic stimulation, we found that (i) optogenetic stimulation of single ocular dominance columns (eye-specific nodes) revealed preferential activation of nearby same-eye columns but not opposite-eye columns, and (ii) optogenetic stimulation of single orientation domains increased visual response of matching orientation domains and relatively suppressed nonmatching orientation selectivity. These findings demonstrate that optical stimulation of single nodes leads to modulation of functionally specific cortical networks related to underlying neural architecture.}, } @article {pmid30257947, year = {2018}, author = {Greenfield, R and Tabib, A and Keshet, I and Moss, J and Sabag, O and Goren, A and Cedar, H}, title = {Role of transcription complexes in the formation of the basal methylation pattern in early development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10387-10391}, pmid = {30257947}, issn = {1091-6490}, mesh = {Animals ; Blastocyst Inner Cell Mass/cytology/*metabolism ; CpG Islands ; *DNA Methylation ; DNA-Directed RNA Polymerases/metabolism ; Embryo, Mammalian/cytology/*metabolism ; *Gene Expression Regulation, Developmental ; Histones/*metabolism ; Mice ; Mice, Transgenic ; Transcription Factors/metabolism ; *Transcription, Genetic ; }, abstract = {Following erasure in the blastocyst, the entire genome undergoes de novo methylation at the time of implantation, with CpG islands being protected from this process. This bimodal pattern is then preserved throughout development and the lifetime of the organism. Using mouse embryonic stem cells as a model system, we demonstrate that the binding of an RNA polymerase complex on DNA before de novo methylation is predictive of it being protected from this modification, and tethering experiments demonstrate that the presence of this complex is, in fact, sufficient to prevent methylation at these sites. This protection is most likely mediated by the recruitment of enzyme complexes that methylate histone H3K4 over a local region and, in this way, prevent access to the de novo methylation complex. The topological pattern of H3K4me3 that is formed while the DNA is as yet unmethylated provides a strikingly accurate template for modeling the genome-wide basal methylation pattern of the organism. These results have far-reaching consequences for understanding the relationship between RNA transcription and DNA methylation.}, } @article {pmid30257946, year = {2018}, author = {Manganaro, L and Hong, P and Hernandez, MM and Argyle, D and Mulder, LCF and Potla, U and Diaz-Griffero, F and Lee, B and Fernandez-Sesma, A and Simon, V}, title = {IL-15 regulates susceptibility of CD4+ T cells to HIV infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9659-E9667}, pmid = {30257946}, issn = {1091-6490}, support = {R01 AI136916/AI/NIAID NIH HHS/United States ; U19 AI118610/AI/NIAID NIH HHS/United States ; R01 AI120998/AI/NIAID NIH HHS/United States ; R56 AI125173/AI/NIAID NIH HHS/United States ; R01 GM113886/GM/NIGMS NIH HHS/United States ; }, mesh = {CD4-Positive T-Lymphocytes/*immunology/pathology/virology ; Disease Susceptibility ; Female ; HEK293 Cells ; HIV Infections/*immunology/pathology ; HIV-1/*immunology ; Humans ; Interleukin-15/*immunology ; Janus Kinase 1/immunology ; Janus Kinase 2/immunology ; Male ; Memory, Short-Term ; Pyrazoles/pharmacology ; SAM Domain and HD Domain-Containing Protein 1/immunology ; }, abstract = {HIV integrates into the host genome to create a persistent viral reservoir. Stimulation of CD4+ memory T lymphocytes with common γc-chain cytokines renders these cells more susceptible to HIV infection, making them a key component of the reservoir itself. IL-15 is up-regulated during primary HIV infection, a time when the HIV reservoir established. Therefore, we investigated the molecular and cellular impact of IL-15 on CD4+ T-cell infection. We found that IL-15 stimulation induces SAM domain and HD domain-containing protein 1 (SAMHD1) phosphorylation due to cell cycle entry, relieving an early block to infection. Perturbation of the pathways downstream of IL-15 receptor (IL-15R) indicated that SAMHD1 phosphorylation after IL-15 stimulation is JAK dependent. Treating CD4+ T cells with Ruxolitinib, an inhibitor of JAK1 and JAK2, effectively blocked IL-15-induced SAMHD1 phosphorylation and protected CD4+ T cells from HIV infection. Using high-resolution single-cell immune profiling using mass cytometry by TOF (CyTOF), we found that IL-15 stimulation altered the composition of CD4+ T-cell memory populations by increasing proliferation of memory CD4+ T cells, including CD4+ T memory stem cells (TSCM). IL-15-stimulated CD4+ TSCM, harboring phosphorylated SAMHD1, were preferentially infected. We propose that IL-15 plays a pivotal role in creating a self-renewing, persistent HIV reservoir by facilitating infection of CD4+ T cells with stem cell-like properties. Time-limited interventions with JAK1 inhibitors, such as Ruxolitinib, should prevent the inactivation of the endogenous restriction factor SAMHD1 and protect this long-lived CD4+ T-memory cell population from HIV infection.}, } @article {pmid30257945, year = {2018}, author = {Liu, HW and Smith, CB and Schmidt, MS and Cambronne, XA and Cohen, MS and Migaud, ME and Brenner, C and Goodman, RH}, title = {Pharmacological bypass of NAD+ salvage pathway protects neurons from chemotherapy-induced degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10654-10659}, pmid = {30257945}, issn = {1091-6490}, support = {DP2 GM126897/GM/NIGMS NIH HHS/United States ; P30 CA086862/CA/NCI NIH HHS/United States ; P30 NS069305/NS/NINDS NIH HHS/United States ; R01 AG055431/AG/NIA NIH HHS/United States ; }, mesh = {Acrylamides/*pharmacology ; Animals ; Antineoplastic Agents, Phytogenic/toxicity ; Drug Combinations ; Francisella tularensis/enzymology ; Ganglia, Spinal/drug effects/metabolism/pathology ; NAD/*metabolism ; Nerve Degeneration/chemically induced/metabolism/*prevention & control ; Neurons/*drug effects/metabolism/pathology ; Niacinamide/*analogs & derivatives/pharmacology ; Nicotinamide Mononucleotide/*analogs & derivatives/metabolism ; Nicotinamide Phosphoribosyltransferase/antagonists & inhibitors/metabolism ; Piperidines/*pharmacology ; Vincristine/*toxicity ; }, abstract = {Axon degeneration, a hallmark of chemotherapy-induced peripheral neuropathy (CIPN), is thought to be caused by a loss of the essential metabolite nicotinamide adenine dinucleotide (NAD+) via the prodegenerative protein SARM1. Some studies challenge this notion, however, and suggest that an aberrant increase in a direct precursor of NAD+, nicotinamide mononucleotide (NMN), rather than loss of NAD+, is responsible. In support of this idea, blocking NMN accumulation in neurons by expressing a bacterial NMN deamidase protected axons from degeneration. We hypothesized that protection could similarly be achieved by reducing NMN production pharmacologically. To achieve this, we took advantage of an alternative pathway for NAD+ generation that goes through the intermediate nicotinic acid mononucleotide (NAMN), rather than NMN. We discovered that nicotinic acid riboside (NAR), a precursor of NAMN, administered in combination with FK866, an inhibitor of the enzyme nicotinamide phosphoribosyltransferase that produces NMN, protected dorsal root ganglion (DRG) axons against vincristine-induced degeneration as well as NMN deamidase. Introducing a different bacterial enzyme that converts NAMN to NMN reversed this protection. Collectively, our data indicate that maintaining NAD+ is not sufficient to protect DRG neurons from vincristine-induced axon degeneration, and elevating NMN, by itself, is not sufficient to cause degeneration. Nonetheless, the combination of FK866 and NAR, which bypasses NMN formation, may provide a therapeutic strategy for neuroprotection.}, } @article {pmid30257944, year = {2018}, author = {Alhadeff, R and Vorobyov, I and Yoon, HW and Warshel, A}, title = {Exploring the free-energy landscape of GPCR activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10327-10332}, pmid = {30257944}, issn = {1091-6490}, support = {R01 AI055926/AI/NIAID NIH HHS/United States ; R35 GM122472/GM/NIGMS NIH HHS/United States ; }, mesh = {Allosteric Regulation ; GTP-Binding Proteins/chemistry/metabolism ; Guanosine Diphosphate/metabolism ; *Models, Molecular ; Protein Conformation ; Receptors, Adrenergic, beta-2/*chemistry/*metabolism ; Receptors, G-Protein-Coupled/chemistry/metabolism ; Signal Transduction ; }, abstract = {G-protein-coupled receptors (GPCRs) are a large group of membrane-bound receptor proteins that are involved in a plethora of diverse processes (e.g., vision, hormone response). In mammals, and particularly in humans, GPCRs are involved in many signal transduction pathways and, as such, are heavily studied for their immense pharmaceutical potential. Indeed, a large fraction of drugs target various GPCRs, and drug-development is often aimed at GPCRs. Therefore, understanding the activation of GPCRs is a challenge of major importance both from fundamental and practical considerations. And yet, despite the remarkable progress in structural understanding, we still do not have a translation of the structural information to an energy-based picture. Here we use coarse-grained (CG) modeling to chart the free-energy landscape of the activation process of the β-2 adrenergic receptor (β2AR) as a representative GPCR. The landscape provides the needed tool for analyzing the processes that lead to activation of the receptor upon binding of the ligand (adrenaline) while limiting constitutive activation. Our results pave the way to better understand the biological mechanisms of action of the β2AR and GPCRs, from a physical chemistry point of view rather than simply by observing the receptor's behavior physiologically.}, } @article {pmid30257943, year = {2018}, author = {Yu, H and Lupoli, TJ and Kovach, A and Meng, X and Zhao, G and Nathan, CF and Li, H}, title = {ATP hydrolysis-coupled peptide translocation mechanism of Mycobacterium tuberculosis ClpB.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9560-E9569}, pmid = {30257943}, issn = {1091-6490}, support = {R01 AI070285/AI/NIAID NIH HHS/United States ; U19 AI111143/AI/NIAID NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/*chemistry/metabolism ; Bacterial Proteins/*chemistry/metabolism ; Endopeptidase Clp/*chemistry/metabolism ; Hydrolysis ; Mycobacterium tuberculosis/*enzymology ; Protein Domains ; Protein Transport ; }, abstract = {The protein disaggregase ClpB hexamer is conserved across evolution and has two AAA+-type nucleotide-binding domains, NBD1 and NBD2, in each protomer. In M. tuberculosis (Mtb), ClpB facilitates asymmetric distribution of protein aggregates during cell division to help the pathogen survive and persist within the host, but a mechanistic understanding has been lacking. Here we report cryo-EM structures at 3.8- to 3.9-Å resolution of Mtb ClpB bound to a model substrate, casein, in the presence of the weakly hydrolyzable ATP mimic adenosine 5'-[γ-thio]triphosphate. Mtb ClpB existed in solution in two closed-ring conformations, conformers 1 and 2. In both conformers, the 12 pore-loops on the 12 NTDs of the six protomers (P1-P6) were arranged similarly to a staircase around the bound peptide. Conformer 1 is a low-affinity state in which three of the 12 pore-loops (the protomer P1 NBD1 and NBD2 loops and the protomer P2 NBD1 loop) are not engaged with peptide. Conformer 2 is a high-affinity state because only one pore-loop (the protomer P2 NBD1 loop) is not engaged with the peptide. The resolution of the two conformations, along with their bound substrate peptides and nucleotides, enabled us to propose a nucleotide-driven peptide translocation mechanism of a bacterial ClpB that is largely consistent with several recent unfoldase structures, in particular with the eukaryotic Hsp104. However, whereas Hsp104's two NBDs move in opposing directions during one step of peptide translocation, in Mtb ClpB the two NBDs move only in the direction of translocation.}, } @article {pmid30257942, year = {2018}, author = {Soeller, C}, title = {Ryanodine receptor cluster size sets the tone in cerebral smooth muscle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10195-10197}, pmid = {30257942}, issn = {1091-6490}, support = {BB/P026508/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R022127/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Caffeine ; Calcium ; Calcium Signaling ; *Muscle, Smooth ; Muscle, Smooth, Vascular ; Ryanodine ; *Ryanodine Receptor Calcium Release Channel ; }, } @article {pmid30257941, year = {2018}, author = {Reese, JM and Bruinsma, ES and Nelson, AW and Chernukhin, I and Carroll, JS and Li, Y and Subramaniam, M and Suman, VJ and Negron, V and Monroe, DG and Ingle, JN and Goetz, MP and Hawse, JR}, title = {ERβ-mediated induction of cystatins results in suppression of TGFβ signaling and inhibition of triple-negative breast cancer metastasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9580-E9589}, pmid = {30257941}, issn = {1091-6490}, support = {P50 CA116201/CA/NCI NIH HHS/United States ; R01 AR068275/AR/NIAMS NIH HHS/United States ; MR/L00156X/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cell Line, Tumor ; Cystatins/genetics/*metabolism ; Estrogen Receptor beta/agonists/genetics/*metabolism ; Female ; Humans ; Mice ; *Signal Transduction ; Transforming Growth Factor beta/genetics/*metabolism ; Triple Negative Breast Neoplasms/drug therapy/genetics/*metabolism/pathology ; Tumor Suppressor Proteins/agonists/genetics/*metabolism ; }, abstract = {Triple-negative breast cancer (TNBC) accounts for a disproportionately high number of deaths due to a lack of targeted therapies and an increased likelihood of distant recurrence. Estrogen receptor beta (ERβ), a well-characterized tumor suppressor, is expressed in 30% of TNBCs, and its expression is associated with improved patient outcomes. We demonstrate that therapeutic activation of ERβ elicits potent anticancer effects in TNBC through the induction of a family of secreted proteins known as the cystatins, which function to inhibit canonical TGFβ signaling and suppress metastatic phenotypes both in vitro and in vivo. These data reveal the involvement of cystatins in suppressing breast cancer progression and highlight the value of ERβ-targeted therapies for the treatment of TNBC patients.}, } @article {pmid30257940, year = {2018}, author = {Jamrog, L and Chemin, G and Fregona, V and Coster, L and Pasquet, M and Oudinet, C and Rouquié, N and Prade, N and Lagarde, S and Cresson, C and Hébrard, S and Nguyen Huu, NS and Bousquet, M and Quelen, C and Brousset, P and Mancini, SJC and Delabesse, E and Khamlichi, AA and Gerby, B and Broccardo, C}, title = {PAX5-ELN oncoprotein promotes multistep B-cell acute lymphoblastic leukemia in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10357-10362}, pmid = {30257940}, issn = {1091-6490}, mesh = {Animals ; B-Lymphocytes/pathology/physiology ; Elastin/*genetics/metabolism ; Gene Expression Regulation, Leukemic ; Gene Knock-In Techniques ; Janus Kinase 3/genetics ; Mice, Transgenic ; Mutation ; Neoplasms, Experimental ; Oncogene Proteins, Fusion/*genetics/metabolism ; PAX5 Transcription Factor/*genetics/metabolism ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*genetics/*pathology ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics ; Proto-Oncogene Proteins p21(ras)/genetics ; }, abstract = {PAX5 is a well-known haploinsufficient tumor suppressor gene in human B-cell precursor acute lymphoblastic leukemia (B-ALL) and is involved in various chromosomal translocations that fuse a part of PAX5 with other partners. However, the role of PAX5 fusion proteins in B-ALL initiation and transformation is ill-known. We previously reported a new recurrent t(7;9)(q11;p13) chromosomal translocation in human B-ALL that juxtaposed PAX5 to the coding sequence of elastin (ELN). To study the function of the resulting PAX5-ELN fusion protein in B-ALL development, we generated a knockin mouse model in which the PAX5-ELN transgene is expressed specifically in B cells. PAX5-ELN-expressing mice efficiently developed B-ALL with an incidence of 80%. Leukemic transformation was associated with recurrent secondary mutations on Ptpn11, Kras, Pax5, and Jak3 genes affecting key signaling pathways required for cell proliferation. Our functional studies demonstrate that PAX5-ELN affected B-cell development in vitro and in vivo featuring an aberrant expansion of the pro-B cell compartment at the preleukemic stage. Finally, our molecular and computational approaches identified PAX5-ELN-regulated gene candidates that establish the molecular bases of the preleukemic state to drive B-ALL initiation. Hence, our study provides a new in vivo model of human B-ALL and strongly implicates PAX5 fusion proteins as potent oncoproteins in leukemia development.}, } @article {pmid30257939, year = {2018}, author = {Gicheru, Y and Chakrapani, S}, title = {Direct visualization of ion-channel gating in a native environment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10198-10200}, pmid = {30257939}, issn = {1091-6490}, support = {R01 GM108921/GM/NIGMS NIH HHS/United States ; }, mesh = {*Ion Channel Gating ; *Protein Conformation ; }, } @article {pmid30257938, year = {2018}, author = {Mach, J and Atkins, M and Gajewski, KM and Mottier-Pavie, V and Sansores-Garcia, L and Xie, J and Mills, RA and Kowalczyk, W and Van Huffel, L and Mills, GB and Halder, G}, title = {Modulation of the Hippo pathway and organ growth by RNA processing proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10684-10689}, pmid = {30257938}, issn = {1091-6490}, support = {P40 OD018537/OD/NIH HHS/United States ; R01 GM067997/GM/NIGMS NIH HHS/United States ; R01 GM084947/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*growth & development/metabolism ; *Gene Expression Regulation, Developmental ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/genetics/metabolism ; Heterogeneous-Nuclear Ribonucleoproteins/genetics/metabolism ; Nuclear Proteins/genetics/*metabolism ; Poly(A)-Binding Protein II/genetics/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Signal Transduction ; Trans-Activators/genetics/*metabolism ; }, abstract = {The Hippo tumor-suppressor pathway regulates organ growth, cell proliferation, and stem cell biology. Defects in Hippo signaling and hyperactivation of its downstream effectors-Yorkie (Yki) in Drosophila and YAP/TAZ in mammals-result in progenitor cell expansion and overgrowth of multiple organs and contribute to cancer development. Deciphering the mechanisms that regulate the activity of the Hippo pathway is key to understanding its function and for therapeutic targeting. However, although the Hippo kinase cascade and several other upstream inputs have been identified, the mechanisms that regulate Yki/YAP/TAZ activity are still incompletely understood. To identify new regulators of Yki activity, we screened in Drosophila for suppressors of tissue overgrowth and Yki activation caused by overexpression of atypical protein kinase C (aPKC), a member of the apical cell polarity complex. In this screen, we identified mutations in the heterogeneous nuclear ribonucleoprotein Hrb27C that strongly suppressed the tissue defects induced by ectopic expression of aPKC. Hrb27C was required for aPKC-induced tissue growth and Yki target gene expression but did not affect general gene expression. Genetic and biochemical experiments showed that Hrb27C affects Yki phosphorylation. Other RNA-binding proteins known to interact with Hrb27C for mRNA transport in oocytes were also required for normal Yki activity, although they suppressed Yki output. Based on the known functions of Hrb27C, we conclude that Hrb27C-mediated control of mRNA splicing, localization, or translation is essential for coordinated activity of the Hippo pathway.}, } @article {pmid30257937, year = {2018}, author = {Chia, S and Habchi, J and Michaels, TCT and Cohen, SIA and Linse, S and Dobson, CM and Knowles, TPJ and Vendruscolo, M}, title = {SAR by kinetics for drug discovery in protein misfolding diseases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10245-10250}, pmid = {30257937}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Alzheimer Disease/*drug therapy/metabolism ; Amyloid beta-Peptides/genetics/*metabolism ; Drug Discovery/*methods ; Humans ; Kinetics ; Peptide Fragments/genetics/*metabolism ; Protein Multimerization/drug effects ; Proteostasis Deficiencies/drug therapy ; Rhodanine/chemistry/pharmacology ; *Structure-Activity Relationship ; }, abstract = {To develop effective therapeutic strategies for protein misfolding diseases, a promising route is to identify compounds that inhibit the formation of protein oligomers. To achieve this goal, we report a structure-activity relationship (SAR) approach based on chemical kinetics to estimate quantitatively how small molecules modify the reactive flux toward oligomers. We use this estimate to derive chemical rules in the case of the amyloid beta peptide (Aβ), which we then exploit to optimize starting compounds to curtail Aβ oligomer formation. We demonstrate this approach by converting an inactive rhodanine compound into an effective inhibitor of Aβ oligomer formation by generating chemical derivatives in a systematic manner. These results provide an initial demonstration of the potential of drug discovery strategies based on targeting directly the production of protein oligomers.}, } @article {pmid30257679, year = {2018}, author = {Luo, X and Song, R and Acar, M}, title = {Multi-component gene network design as a survival strategy in diverse environments.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {85}, pmid = {30257679}, issn = {1752-0509}, support = {DP2 AG050461/AG/NIA NIH HHS/United States ; U54 CA209992/CA/NCI NIH HHS/United States ; 1DP2AG050461-01//National Institute on Aging (US)/ ; 1U54CA209992-01//National Cancer Institute/ ; }, abstract = {BACKGROUND: Gene-environment interactions are often mediated though gene networks in which gene expression products interact with other network components to dictate network activity levels, which in turn determines the fitness of the host cell in specific environments. Even though a gene network is the right context for studying gene-environment interactions, we have little understanding on how systematic genetic perturbations affects fitness in the context of a gene network.

RESULTS: Here we examine the effect of combinatorial gene dosage alterations on gene network activity and cellular fitness. Using the galactose utilization pathway as a model network in diploid yeast, we reduce the copy number of four regulatory genes (GAL2, GAL3, GAL4, GAL80) from two to one, and measure the activity of the perturbed networks. We integrate these results with competitive fitness measurements made in six different rationally-designed environments containing different galactose concentrations representing the natural induction spectrum of the galactose network. In the lowest galactose environment, we find a nonlinear relationship between gene expression and fitness while high galactose environments lead to a linear relationship between the two with a saturation regime reached at a sufficiently high galactose concentration. We further uncover environment-specific relevance of the different network components for dictating the relationship between the network activity and organismal fitness, indicating that none of the network components are redundant.

CONCLUSIONS: These results provide experimental support to the hypothesis that dynamic changes in the environment throughout natural evolution is key to structuring natural gene networks in a multi-component fashion, which robustly provides protection against population extinction in different environments.}, } @article {pmid30257674, year = {2018}, author = {Rowe, E and Palsson, BO and King, ZA}, title = {Escher-FBA: a web application for interactive flux balance analysis.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {84}, pmid = {30257674}, issn = {1752-0509}, support = {NNF10CC1016517//Novo Nordisk/ ; }, abstract = {BACKGROUND: Flux balance analysis (FBA) is a widely-used method for analyzing metabolic networks. However, most existing tools that implement FBA require downloading software and writing code. Furthermore, FBA generates predictions for metabolic networks with thousands of components, so meaningful changes in FBA solutions can be difficult to identify. These challenges make it difficult for beginners to learn how FBA works.

RESULTS: To meet this need, we present Escher-FBA, a web application for interactive FBA simulations within a pathway visualization. Escher-FBA allows users to set flux bounds, knock out reactions, change objective functions, upload metabolic models, and generate high-quality figures without downloading software or writing code. We provide detailed instructions on how to use Escher-FBA to replicate several FBA simulations that generate real scientific hypotheses.

CONCLUSIONS: We designed Escher-FBA to be as intuitive as possible so that users can quickly and easily understand the core concepts of FBA. The web application can be accessed at https://sbrg.github.io/escher-fba .}, } @article {pmid30257653, year = {2018}, author = {Sweetnam, C and Mocellin, S and Krauthammer, M and Knopf, N and Baertsch, R and Shrager, J}, title = {Prototyping a precision oncology 3.0 rapid learning platform.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {341}, pmid = {30257653}, issn = {1471-2105}, mesh = {Algorithms ; Education, Medical ; Humans ; *Medical Oncology ; *Precision Medicine ; Publications ; *Software ; }, abstract = {BACKGROUND: We describe a prototype implementation of a platform that could underlie a Precision Oncology Rapid Learning system.

RESULTS: We describe the prototype platform, and examine some important issues and details. In the Appendix we provide a complete walk-through of the prototype platform.

CONCLUSIONS: The design choices made in this implementation rest upon ten constitutive hypotheses, which, taken together, define a particular view of how a rapid learning medical platform might be defined, organized, and implemented.}, } @article {pmid30257651, year = {2018}, author = {Oliphant, A and Alexander, JL and Swain, MT and Webster, SG and Wilcockson, DC}, title = {Transcriptomic analysis of crustacean neuropeptide signaling during the moult cycle in the green shore crab, Carcinus maenas.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {711}, pmid = {30257651}, issn = {1471-2164}, support = {BB/L021242/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L021552/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Arthropod Proteins/genetics ; Brachyura/genetics/*growth & development ; Central Nervous System/chemistry ; Ecdysteroids/genetics ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental ; Molting ; Neuropeptides/*genetics ; Receptors, G-Protein-Coupled/*genetics ; Sequence Analysis, RNA/methods ; Signal Transduction ; }, abstract = {BACKGROUND: Ecdysis is an innate behaviour programme by which all arthropods moult their exoskeletons. The complex suite of interacting neuropeptides that orchestrate ecdysis is well studied in insects, but details of the crustacean ecdysis cassette are fragmented and our understanding of this process is comparatively crude, preventing a meaningful evolutionary comparison. To begin to address this issue we identified transcripts coding for neuropeptides and their putative receptors in the central nervous system (CNS) and Y-organs (YO) within the crab, Carcinus maenas, and mapped their expression profiles across accurately defined stages of the moult cycle using RNA-sequencing. We also studied gene expression within the epidermally-derived YO, the only defined role for which is the synthesis of ecdysteroid moulting hormones, to elucidate peptides and G protein-coupled receptors (GPCRs) that might have a function in ecdysis.

RESULTS: Transcriptome mining of the CNS transcriptome yielded neuropeptide transcripts representing 47 neuropeptide families and 66 putative GPCRs. Neuropeptide transcripts that were differentially expressed across the moult cycle included carcikinin, crustacean hyperglycemic hormone-2, and crustacean cardioactive peptide, whilst a single putative neuropeptide receptor, proctolin R1, was differentially expressed. Carcikinin mRNA in particular exhibited dramatic increases in expression pre-moult, suggesting a role in ecdysis regulation. Crustacean hyperglycemic hormone-2 mRNA expression was elevated post- and pre-moult whilst that for crustacean cardioactive peptide, which regulates insect ecdysis and plays a role in stereotyped motor activity during crustacean ecdysis, was elevated in pre-moult. In the YO, several putative neuropeptide receptor transcripts were differentially expressed across the moult cycle, as was the mRNA for the neuropeptide, neuroparsin-1. Whilst differential gene expression of putative neuropeptide receptors was expected, the discovery and differential expression of neuropeptide transcripts was surprising. Analysis of GPCR transcript expression between YO and epidermis revealed 11 to be upregulated in the YO and thus are now candidates for peptide control of ecdysis.

CONCLUSIONS: The data presented represent a comprehensive survey of the deduced C. maenas neuropeptidome and putative GPCRs. Importantly, we have described the differential expression profiles of these transcripts across accurately staged moult cycles in tissues key to the ecdysis programme. This study provides important avenues for the future exploration of functionality of receptor-ligand pairs in crustaceans.}, } @article {pmid30257650, year = {2018}, author = {Cheng, D and Tan, M and Yu, H and Li, L and Zhu, D and Chen, Y and Jiang, M}, title = {Comparative analysis of Cd-responsive maize and rice transcriptomes highlights Cd co-modulated orthologs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {709}, pmid = {30257650}, issn = {1471-2164}, support = {31271421//National Natural Science Foundation of China (CN)/ ; }, mesh = {Base Sequence ; Cadmium/*pharmacology ; Conserved Sequence ; Evolution, Molecular ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant/drug effects ; Gene Regulatory Networks/drug effects ; Oryza/drug effects/*genetics ; Plant Proteins/*genetics ; Sequence Analysis, RNA/methods ; Zea mays/drug effects/*genetics ; }, abstract = {BACKGROUND: Metal tolerance is often an integrative result of metal uptake and distribution, which are fine-tuned by a network of signaling cascades and metal transporters. Thus, with the goal of advancing the molecular understanding of such metal homeostatic mechanisms, comparative RNAseq-based transcriptome analysis was conducted to dissect differentially expressed genes (DEGs) in maize roots exposed to cadmium (Cd) stress.

RESULTS: To unveil conserved Cd-responsive genes in cereal plants, the obtained 5166 maize DEGs were compared with 2567 Cd-regulated orthologs in rice roots, and this comparison generated 880 universal Cd-responsive orthologs groups composed of 1074 maize DEGs and 981 rice counterparts. More importantly, most of the orthologous DEGs showed coordinated expression pattern between Cd-treated maize and rice, and these include one large orthologs group of pleiotropic drug resistance (PDR)-type ABC transporters, two clusters of amino acid transporters, and 3 blocks of multidrug and toxic compound extrusion (MATE) efflux family transporters, and 3 clusters of heavy metal-associated domain (HMAD) isoprenylated plant proteins (HIPPs), as well as all 4 groups of zinc/iron regulated transporter protein (ZIPs). Additionally, several blocks of tandem maize paralogs, such as germin-like proteins (GLPs), phenylalanine ammonia-lyases (PALs) and several enzymes involved in JA biosynthesis, displayed consistent co-expression pattern under Cd stress. Out of the 1074 maize DEGs, approximately 30 maize Cd-responsive genes such as ZmHIPP27, stress-responsive NAC transcription factor (ZmSNAC1) and 9-cis-epoxycarotenoid dioxygenase (NCED, vp14) were also common stress-responsive genes reported to be uniformly regulated by multiple abiotic stresses. Moreover, the aforementioned three promising Cd-upregulated genes with rice counterparts were identified to be novel Cd-responsive genes in maize. Meanwhile, one maize glutamate decarboxylase (ZmGAD1) with Cd co-modulated rice ortholog was selected for further analysis of Cd tolerance via heterologous expression, and the results suggest that ZmGAD1 can confer Cd tolerance in yeast and tobacco leaves.

CONCLUSIONS: These novel findings revealed the conserved function of Cd-responsive orthologs and paralogs, which would be valuable for elucidating the genetic basis of the plant response to Cd stress and unraveling Cd tolerance genes.}, } @article {pmid30257645, year = {2018}, author = {Awan, F and Dong, Y and Liu, J and Wang, N and Mushtaq, MH and Lu, C and Liu, Y}, title = {Comparative genome analysis provides deep insights into Aeromonas hydrophila taxonomy and virulence-related factors.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {712}, pmid = {30257645}, issn = {1471-2164}, support = {31372454//National Nature Science Foundation of China/ ; CX(17)2027//Independent Innovation Fund of Agricultural Science and Technology in Jiangsu Province/ ; D2017-3-1//Jiangsu fishery science and technology project/ ; }, mesh = {Aeromonas hydrophila/*classification/*genetics/pathogenicity ; Bacterial Proteins/*genetics ; Computational Biology ; Computer Simulation ; Drug Resistance, Bacterial ; Genome, Bacterial ; Molecular Typing ; Phylogeny ; Sequence Analysis, DNA/*methods ; Virulence Factors/genetics ; }, abstract = {BACKGROUND: Aeromonas hydrophila is a potential zoonotic pathogen and primary fish pathogen. With overlapping characteristics, multiple isolates are often mislabelled and misclassified. Moreover, the potential pathogenic factors among the publicly available genomes in A. hydrophila strains of different origins have not yet been investigated.

RESULTS: To identify the valid strains of A. hydrophila and their pathogenic factors, we performed a pan-genomic study. It revealed that there were 13 mislabelled strains and 49 valid strains that were further verified by Average nucleotide identity (ANI), digital DNA-DNA hybridization (dDDH) and in silico multiple locus strain typing (MLST). Multiple numbers of phages were detected among the strains and among them Aeromonas phi 018 was frequently present. The diversity in type III secretion system (T3SS) and conservation of type II and type VI secretion systems (T2SS and T6SS, respectively) among all the strains are important to study for designing future strategies. The most prevalent antibiotic resistances were found to be beta-lactamase, polymyxin and colistin resistances. The comparative analyses of sequence type (ST) 251 and other ST groups revealed that there were higher numbers of virulence factors in ST-251 than in other STs group.

CONCLUSION: Publicly available genomes have 13 mislabelled organisms, and there are only 49 valid A. hydrophila strains. This valid pan-genome identifies multiple prophages that can be further utilized. Different A. hydrophila strains harbour multiple virulence factors and antibiotic resistance genes. Identification of such factors is important for designing future treatment regimes.}, } @article {pmid30257644, year = {2018}, author = {Li, W and Liu, Y and Yang, Y and Xie, X and Lu, Y and Yang, Z and Jin, X and Dong, W and Suo, Z}, title = {Interspecific chloroplast genome sequence diversity and genomic resources in Diospyros.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {210}, pmid = {30257644}, issn = {1471-2229}, support = {LKZ201496-1-3//Shandong Provincial Agricultural/ ; }, mesh = {DNA, Chloroplast ; Diospyros/*genetics ; Genetic Markers ; Genetic Variation ; *Genome, Chloroplast ; *Phylogeny ; }, abstract = {BACKGROUND: Fruits of persimmon plants are traditional healthy food in China, Korea and Japan. However, due to the shortage of morphological and DNA markers, the development of persimmon industry has been heavily inhibited.

RESULTS: Chloroplast genomes of Diospyros cathayensis, D. virginiana, D. rhombifolia and D. deyangensis were newly sequenced. Comparative analyses of ten chloroplast genomes including six previously published chloroplast genomes of Diospyros provided new insights into the genome sequence diversity and genomic resources of the genus. Eight hyper-variable regions, trnH-psbA, rps16-trnQ, rpoB-trnC, rps4-trnT-trnL, ndhF, ndhF-rpl32-trnL, ycf1a, and ycf1b, were discovered and can be used as chloroplast DNA markers at/above species levels. The complete chloroplast genome sequences provided the best resolution at inter-specific level in comparison with different chloroplast DNA sequence datasets.

CONCLUSION: Diospyros oleifera, D. deyangensis, D. virginiana, D. glaucifolia, D. lotus and D. jinzaoshi are important wild species closely related to the cultivated persimmon D. kaki. The hyper-variable regions can be used as DNA markers for global genetic diversity detection of Diospyros. Deeper study on these taxa would be helpful for elucidating the origin of D. kaki.}, } @article {pmid30257643, year = {2018}, author = {Guo, J and Chen, J and Yang, J and Yu, Y and Yang, Y and Wang, W}, title = {Identification, characterization and expression analysis of the VQ motif-containing gene family in tea plant (Camellia sinensis).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {710}, pmid = {30257643}, issn = {1471-2164}, support = {2016M602873//China Postdoctoral Science Foundation/ ; 2452017074//Fundamental Research Funds for the Central Universities/ ; CARS-19//earmarked fund for Modern Agro-industry Technology Research System/ ; }, mesh = {Amino Acid Motifs ; Camellia sinensis/*genetics/growth & development ; Cell Nucleus/*metabolism ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Gene Regulatory Networks ; MicroRNAs/metabolism ; Multigene Family ; Plant Proteins/chemistry/genetics ; Trans-Activators/chemistry/*genetics/*metabolism ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: VQ motif-containing (VQ) proteins are plant-specific proteins that interact with WRKY transcription factors and play important roles in plant growth, development and stress response. To date, VQ gene families have been identified and characterized in many plant species, including Arabidopsis, rice and grapevine. However, the VQ gene family in tea plant has not been reported, and the biological functions of this family remain unknown.

RESULTS: In total, 25 CsVQ genes were identified based on the genome and transcriptome of tea plant, and a comprehensive bioinformatics analysis was performed. The CsVQ proteins all contained the typical conserved motif FxxhVQxhTG, and most proteins were localized in the nucleus. The phylogenetic analysis showed that the VQ proteins were classified into 5 groups (I, III-VI); the evolution of the CsVQ proteins is consistent with the evolutionary process of plants, and close proteins shared similar structures and functions. In addition, the expression analysis revealed that the CsVQ genes play important roles in the process of tea plant growth, development and response to salt and drought stress. Furthermore, a potential regulatory network including the interactions of CsVQ proteins with CsWRKY transcription factors and the regulation of upstream microRNA that is closely related to the above-mentioned processes is proposed.

CONCLUSIONS: The results of this study increase our understanding and characterization of CsVQ genes and their encoded proteins in tea plant. This systematic analysis provided comprehensive information for further studies investigating the biological functions of CsVQ proteins in various developmental processes of tea plants.}, } @article {pmid30257640, year = {2018}, author = {Sheikhizadeh Anari, S and de Ridder, D and Schranz, ME and Smit, S}, title = {Efficient inference of homologs in large eukaryotic pan-proteomes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {340}, pmid = {30257640}, issn = {1471-2105}, support = {3184519600//Experimental Plant Sciences/ ; }, mesh = {Algorithms ; Brassicaceae/genetics ; Cluster Analysis ; Databases, Protein ; Eukaryota/*metabolism ; Genes, Plant ; Genome ; Genomics ; Humans ; Proteome/*metabolism ; Sequence Homology, Amino Acid ; Software ; }, abstract = {BACKGROUND: Identification of homologous genes is fundamental to comparative genomics, functional genomics and phylogenomics. Extensive public homology databases are of great value for investigating homology but need to be continually updated to incorporate new sequences. As new sequences are rapidly being generated, there is a need for efficient standalone tools to detect homologs in novel data.

RESULTS: To address this, we present a fast method for detecting homology groups across a large number of individuals and/or species. We adopted a k-mer based approach which considerably reduces the number of pairwise protein alignments without sacrificing sensitivity. We demonstrate accuracy, scalability, efficiency and applicability of the presented method for detecting homology in large proteomes of bacteria, fungi, plants and Metazoa.

CONCLUSIONS: We clearly observed the trade-off between recall and precision in our homology inference. Favoring recall or precision strongly depends on the application. The clustering behavior of our program can be optimized for particular applications by altering a few key parameters. The program is available for public use at https://github.com/sheikhizadeh/pantools as an extension to our pan-genomic analysis tool, PanTools.}, } @article {pmid30257073, year = {2018}, author = {Smolla, M and Invernizzi, E and Bazhydai, M and Casoli, M and Deffner, D and Faria, GS and Jones, N and Kanwal, J and Staehler, AM and Uchiyama, R}, title = {Second annual workshop of the Association of Early-Career Social Learning Researchers in St Andrews, Scotland.}, journal = {Evolutionary anthropology}, volume = {27}, number = {5}, pages = {184-187}, doi = {10.1002/evan.21746}, pmid = {30257073}, issn = {1520-6505}, } @article {pmid30257046, year = {2018}, author = {Wilks, CEH and Blakey, KH}, title = {In the jungle of cultural complexity.}, journal = {Evolutionary anthropology}, volume = {27}, number = {5}, pages = {180-183}, doi = {10.1002/evan.21724}, pmid = {30257046}, issn = {1520-6505}, support = {648841 RATCHETCOG ERC-2014-CoG//European Research Council/International ; }, } @article {pmid30257042, year = {2018}, author = {Rajkov, J and Weber, AA and Salzburger, W and Egger, B}, title = {Immigrant and extrinsic hybrid inviability contribute to reproductive isolation between lake and river cichlid ecotypes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2553-2564}, doi = {10.1111/evo.13612}, pmid = {30257042}, issn = {1558-5646}, support = {31003A_156405//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; //Swiss Zoological Society/ ; }, abstract = {Understanding how reproductive barriers evolve and which barriers contribute to speciation requires the examination of organismal lineages that are still in the process of diversification and the study of the full range of reproductive barriers acting at different life stages. Lake and river ecotypes of the East African cichlid fish Astatotilapia burtoni show habitat-specific adaptations, despite different levels of genetic differentiation, and thus represent an ideal model to study the evolution of reproductive barriers. To evaluate the degree of reproductive isolation between genetically divergent lake and river populations, we performed a mesocosm mating experiment in a semi-natural setting at Lake Tanganyika. We assessed reproductive isolation in the presence of male-male competition by analyzing survival and growth rates of introduced adults and their reproductive success from genetic parentage of surviving offspring. The genetically divergent river population showed reduced fitness in terms of survival, growth rate, and mating success in a lake-like environment. Hybrid offspring between different populations showed intermediate survival consistent with extrinsic postzygotic reproductive barriers. Our results suggest that both prezygotic (immigrant inviability) and postzygotic reproductive barriers contribute to divergence, and highlight the value of assessing multiple reproductive barriers acting at different stages and in natural contexts to understand speciation mechanisms.}, } @article {pmid30257040, year = {2018}, author = {Budd, GE and Mann, RP}, title = {History is written by the victors: The effect of the push of the past on the fossil record.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2276-2291}, pmid = {30257040}, issn = {1558-5646}, support = {//Vetenskapsrådet/ ; }, abstract = {Survivorship biases can generate remarkable apparent rate heterogeneities through time in otherwise homogeneous birth-death models of phylogenies. They are a potential explanation for many striking patterns seen in the fossil record and molecular phylogenies. One such bias is the "push of the past": clades that survived a substantial length of time are likely to have experienced a high rate of early diversification. This creates the illusion of a secular rate slow-down through time that is, rather, a reversion to the mean. An extra effect increasing early rates of lineage generation is also seen in large clades. These biases are important but relatively neglected influences on many aspects of diversification patterns in the fossil record and elsewhere, such as diversification spikes after mass extinctions and at the origins of clades; they also influence rates of fossilization, changes in rates of phenotypic evolution and even molecular clocks. These inevitable features of surviving and/or large clades should thus not be generalized to the diversification process as a whole without additional study of small and extinct clades, and raise questions about many of the traditional explanations of the patterns seen in the fossil record.}, } @article {pmid30257033, year = {2018}, author = {Schiestl, FP and Balmer, A and Gervasi, DD}, title = {Real-time evolution supports a unique trajectory for generalized pollination.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2653-2668}, doi = {10.1111/evo.13611}, pmid = {30257033}, issn = {1558-5646}, support = {FP7/2007-2013//European Union's Seventh Framework Program/ ; FP7/2007-2011//European Union's Seventh Framework Program/ ; PDAMP3-127227/1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 281093//H2020 European Research Council/ ; }, abstract = {Whereas specialized pollination is well recognized to cause floral adaptation, we know little about the evolutionary impact of generalized pollination. For example, it is largely unknown whether such pollination can lead to adaptive floral divergence and to what degree pollinators with different effectiveness determine evolutionary trajectories. Here, we investigated the evolutionary consequences of combined bumblebee- and hoverfly-pollination ("generalized" pollination) in comparison with those of each individual pollinator species (specialized pollination), using fast-cycling Brassica rapa plants during seven generations of experimental evolution. Bumblebees were twice as efficient as hoverflies in pollinating B. rapa flowers, but phenotypic selection and evolutionary change in plants with generalized pollination was different from both bumblebee- and hoverfly-pollinated plants for several traits. After seven generations evolution, plants with generalized pollination resembled bumblebee-pollinated plants in having little spontaneous selfing and tall size, but were more similar to hoverfly-pollinated plants in having low floral scent emission. This unique trait combination supports the idea of a generalized-pollination ecotype, coined neither by the most efficient pollinator, nor by an evolutionary average between the changes caused by each individual pollinator. For a better understanding of such "nonadditive evolution," future research should target interactions of pollinators and their effect on phenotypic selection.}, } @article {pmid30256993, year = {2018}, author = {Langer, BE and Roscito, JG and Hiller, M}, title = {REforge Associates Transcription Factor Binding Site Divergence in Regulatory Elements with Phenotypic Differences between Species.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {3027-3040}, pmid = {30256993}, issn = {1537-1719}, abstract = {Elucidating the genomic determinants of morphological differences between species is key to understanding how morphological diversity evolved. While differences in cis-regulatory elements are an important genetic source for morphological evolution, it remains challenging to identify regulatory elements involved in phenotypic differences. Here, we present Regulatory Element forward genomics (REforge), a computational approach that detects associations between transcription factor binding site divergence in putative regulatory elements and phenotypic differences between species. By simulating regulatory element evolution in silico, we show that this approach has substantial power to detect such associations. To validate REforge on real data, we used known binding motifs for eye-related transcription factors and identified significant binding site divergence in vision-impaired subterranean mammals in 1% of all conserved noncoding elements. We show that these genomic regions are significantly enriched in regulatory elements that are specifically active in mouse eye tissues, and that several of them are located near genes, which are required for eye development and photoreceptor function and are implicated in human eye disorders. Thus, our genome-wide screen detects widespread divergence of eye-regulatory elements and highlights regulatory regions that likely contributed to eye degeneration in subterranean mammals. REforge has broad applicability to detect regulatory elements that could be involved in many other phenotypes, which will help to reveal the genomic basis of morphological diversity.}, } @article {pmid30256937, year = {2018}, author = {Romero, V and Nakaoka, H and Hosomichi, K and Inoue, I}, title = {High Order Formation and Evolution of Hornerin in Primates.}, journal = {Genome biology and evolution}, volume = {10}, number = {12}, pages = {3167-3175}, pmid = {30256937}, issn = {1759-6653}, abstract = {Genomic duplication or loss can accelerate evolution because the number of repeats could affect molecular pathways and phenotypes. We have previously reported that the repeated region of filaggrin (FLG), a crucial component of the outer layers of mammalian skin, had high levels of nucleotide diversity with species-specific divergence and expansion and that it evolved under the birth-and-death model. We focused on hornerin (HRNR), a member of the same gene family that harbor similar tandem repeats as FLG, and examined the formation process of repeated regions and the evolutional model that best fit the HRNR repeated region in the crab-eating macaque (Macaca fascicularis), orangutan (Pongo abelii), gorilla (Gorilla gorilla), and chimpanzee (Pan troglodytes) and compared them with the human (Homo sapiens) sequence. Paar et al. (2011) and Takaishi et al. (2005) have different theories as to the formation of the repeated region of HRNR; both groups share the longest repeat length of 1,404 bp (quartic or longest unit), but they differed in the process. We identified the formation described by Paar et al. {[("39 bp (primary) × 9" × 2 (secondary)) × 2 (tertiary)] × 5 (quartic)} to be conserved in all species except the crab-eating macaque. We detected high nucleotide diversities between the longest repeats, which fits the birth-and-death model. We concluded that the high order repeat formation of HRNR was conserved in primates except the crab-eating macaque. As previously identified in FLG, the longest repeats have high levels of nucleotide diversity, which could contribute to phenotypic differences between closely related species.}, } @article {pmid30256677, year = {2018}, author = {Galupa, R and Heard, E}, title = {X-Chromosome Inactivation: A Crossroads Between Chromosome Architecture and Gene Regulation.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {535-566}, doi = {10.1146/annurev-genet-120116-024611}, pmid = {30256677}, issn = {1545-2948}, abstract = {In somatic nuclei of female therian mammals, the two X chromosomes display very different chromatin states: One X is typically euchromatic and transcriptionally active, and the other is mostly silent and forms a cytologically detectable heterochromatic structure termed the Barr body. These differences, which arise during female development as a result of X-chromosome inactivation (XCI), have been the focus of research for many decades. Initial approaches to define the structure of the inactive X chromosome (Xi) and its relationship to gene expression mainly involved microscopy-based approaches. More recently, with the advent of genomic techniques such as chromosome conformation capture, molecular details of the structure and expression of the Xi have been revealed. Here, we review our current knowledge of the 3D organization of the mammalian X-chromosome chromatin and discuss its relationship with gene activity in light of the initiation, spreading, and maintenance of XCI, as well as escape from gene silencing.}, } @article {pmid30256489, year = {2018}, author = {Galván, I}, title = {Predation risk determines pigmentation phenotype in nuthatches by melanin-related gene expression effects.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1760-1771}, doi = {10.1111/jeb.13379}, pmid = {30256489}, issn = {1420-9101}, support = {//Spanish National Research Council (CSIC)/ ; CGL2015-67796-P//Spanish Ministry of Economy and Competitiveness (MINECO)/ ; RYC-2012-10237//Spanish Ministry of Economy and Competitiveness (MINECO)/ ; //Ramón y Cajal Fellowship/ ; }, abstract = {Pigments determine the appearance of organisms. However, pigment production can be associated with physiological constraints as in the case of pheomelanin, the sulphurated form of melanin whose synthesis in melanocytes consumes cysteine and consequently reduces the availability of glutathione (GSH) to exert antioxidant protection. Pheomelanogenesis may thus increase the susceptibility to suffer chronic oxidative stress. I investigated the possibility that environmental lability in the expression of genes regulating pheomelanogenesis protects from oxidative stress, a situation in which GSH is most required. By broadcasting adult alarm calls, I manipulated the perception of predation risk, a natural source of oxidative stress, in free-living Eurasian nuthatch Sitta europaea nestlings developing pheomelanin-pigmented flank feathers. The manipulation affected the consumption of GSH that resulted from the expression of two genes (Slc7a11 and Slc45a2) influencing cysteine/GSH availability in cells, as these genes were down-regulated in the feather melanocytes of the nestlings with lowest intracellular antioxidant capacity (i.e. lowest GSH levels). Systemic oxidative damage increased with Slc7a11 expression in feather melanocytes, suggesting that the observed down-regulation was physiologically advantageous. The nestlings exposed to an increased perception of predation risk developed flank feathers of reduced colour intensity. These results indicate that perceived predation risk can determine the pigmentation phenotype by (probably epigenetic) effects on gene expression that protect from physiological constraints imposed by pheomelanin production.}, } @article {pmid30256485, year = {2018}, author = {Ng, J and Smith, SD}, title = {Why are red flowers so rare? Testing the macroevolutionary causes of tippiness.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1863-1875}, doi = {10.1111/jeb.13381}, pmid = {30256485}, issn = {1420-9101}, support = {1413855//NSF-DEB/ ; 1553114//NSF-DEB/ ; CNS-0821794//National Science Foundation/ ; //University of Colorado Boulder/ ; }, abstract = {Traits that have arisen multiple times yet still remain rare present a curious paradox. A number of these rare traits show a distinct tippy pattern, where they appear widely dispersed across a phylogeny, are associated with short branches and differ between recently diverged sister species. This phylogenetic pattern has classically been attributed to the trait being an evolutionary dead end, where the trait arises due to some short-term evolutionary advantage, but it ultimately leads species to extinction. While the higher extinction rate associated with a dead end trait could produce such a tippy pattern, a similar pattern could appear if lineages with the trait speciated slower than other lineages, or if the trait was lost more often that it was gained. In this study, we quantify the degree of tippiness of red flowers in the tomato family, Solanaceae, and investigate the macroevolutionary processes that could explain the sparse phylogenetic distribution of this trait. Using a suite of metrics, we confirm that red-flowered lineages are significantly overdispersed across the tree and form smaller clades than expected under a null model. Next, we fit 22 alternative models using HiSSE (Hidden State Speciation and Extinction), which accommodates asymmetries in speciation, extinction and transition rates that depend on observed and unobserved (hidden) character states. Results of the model fitting indicated significant variation in diversification rates across the family, which is best explained by the inclusion of hidden states. Our best fitting model differs between the maximum clade credibility tree and when incorporating phylogenetic uncertainty, suggesting that the extreme tippiness and rarity of red Solanaceae flowers makes it difficult to distinguish among different underlying processes. However, both of the best models strongly support a bias towards the loss of red flowers. The best fitting HiSSE model when incorporating phylogenetic uncertainty lends some support to the hypothesis that lineages with red flowers exhibit reduced diversification rates due to elevated extinction rates. Future studies employing simulations or targeting population-level processes may allow us to determine whether red flowers in Solanaceae or other angiosperms clades are rare and tippy due to a combination of processes, or asymmetrical transitions alone.}, } @article {pmid30256481, year = {2018}, author = {Enriquez-Urzelai, U and Palacio, AS and Merino, NM and Sacco, M and Nicieza, AG}, title = {Hindered and constrained: limited potential for thermal adaptation in post-metamorphic and adult Rana temporaria along elevational gradients.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1852-1862}, doi = {10.1111/jeb.13380}, pmid = {30256481}, issn = {1420-9101}, support = {CGL2012-40246-C02-02//MINECO/ ; BES-2013-063203//MINECO/ ; }, abstract = {Adaptation to warming climates could counteract the effects of global warming. Thus, understanding how species cope with contrasting climates may inform us about their potential for thermal adaptation and which processes may hamper that ability (e.g. evolutionary trade-offs, phenology or behavioural thermoregulation). In addition to temperature, time constraints may also exert important selective pressures. Here, we compare the thermal sensitivity of locomotion of metamorphic and adult European common frogs (Rana temporaria) originating from populations along an elevational gradient. We employed the template mode of variation (TMV) analysis to decompose the thermal sensitivity of locomotion and explore the existence of trade-offs ('hotter is better' and 'specialist-generalist') and the degree of local adaptation. To that end, we studied the relationship between TMV parameters and local environmental conditions. Further, we compared preferred temperatures to assess whether behavioural thermoregulation could dampen the effects of thermal variation, reducing the intensity of selection and limiting thermal adaptation (i.e. 'Bogert effect'). We suggest that behavioural thermoregulation has promoted the conservatism of thermal sensitivity in R. temporaria. Yet, we observed a trend towards narrower thermal niches shifted towards warmer temperature in populations with severe temporal constraints, conforming to the 'generalist-specialist' trade-off. Apparently, this enables time-constrained populations - especially in the case of metamorphs - to effectively exploit resources during the warmest periods. The limited potential of R. temporaria for thermal adaptation suggests that forecasts of global warming should incorporate thermoregulation and explore its potential to buffer species from rising temperatures.}, } @article {pmid30255820, year = {2018}, author = {Cherlin, S and Wang, MH and Bickeböller, H and Cantor, RM}, title = {Detecting responses to treatment with fenofibrate in pedigrees.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {64}, pmid = {30255820}, issn = {1471-2156}, support = {//Wellcome Trust/United Kingdom ; P01 HL028481/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Fenofibrate (Fb) is a known treatment for elevated triglyceride (TG) levels. The Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study was designed to investigate potential contributors to the effects of Fb on TG levels. Here, we summarize the analyses of 8 papers whose authors had access to the GOLDN data and were grouped together because they pursued investigations into Fb treatment responses as part of GAW20. These papers report explorations of a variety of genetics, epigenetics, and study design questions. Data regarding treatment with 160 mg of micronized Fb per day for 3 weeks included pretreatment and posttreatment TG and methylation levels (ML) at approximately 450,000 epigenetic markers (cytosine-phosphate-guanine [CpG] sites). In addition, approximately 1 million single-nucleotide polymorphisms (SNPs) were genotyped or imputed in each of the study participants, drawn from 188 pedigrees.

RESULTS: The analyses of a variety of subsets of the GOLDN data used a number of analytic approaches such as linear mixed models, a kernel score test, penalized regression, and artificial neural networks.

CONCLUSIONS: Results indicate that (a) CpG ML are responsive to Fb; (b) CpG ML should be included in models predicting the TG level responses to Fb;}, } @article {pmid30255819, year = {2018}, author = {de Andrade, M and Warwick Daw, E and Kraja, AT and Fisher, V and Wang, L and Hu, K and Li, J and Romanescu, R and Veenstra, J and Sun, R and Weng, H and Zhou, W}, title = {The challenge of detecting genotype-by-methylation interaction: GAW20.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {81}, pmid = {30255819}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: GAW20 working group 5 brought together researchers who contributed 7 papers with the aim of evaluating methods to detect genetic by epigenetic interactions. GAW20 distributed real data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study, including single-nucleotide polymorphism (SNP) markers, methylation (cytosine-phosphate-guanine [CpG]) markers, and phenotype information on up to 995 individuals. In addition, a simulated data set based on the real data was provided.

RESULTS: The 7 contributed papers analyzed these data sets with a number of different statistical methods, including generalized linear mixed models, mediation analysis, machine learning, W-test, and sparsity-inducing regularized regression. These methods generally appeared to perform well. Several papers confirmed a number of causative SNPs in either the large number of simulation sets or the real data on chromosome 11. Findings were also reported for different SNPs, CpG sites, and SNP-CpG site interaction pairs.

CONCLUSIONS: In the simulation (200 replications), power appeared generally good for large interaction effects, but smaller effects will require larger studies or consortium collaboration for realizing a sufficient power.}, } @article {pmid30255818, year = {2018}, author = {Ghosh, S and Fardo, DW}, title = {Association analyses of repeated measures on triglyceride and high-density lipoprotein levels: insights from GAW20.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {73}, pmid = {30255818}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: The GAW20 group formed on the theme of methods for association analyses of repeated measures comprised 4sets of investigators. The provided "real" data set included genotypes obtained from a human whole-genome association study based on longitudinal measurements of triglycerides (TGs) and high-density lipoprotein in addition to methylation levels before and after administration of fenofibrate. The simulated data set contained 200 replications of methylation levels and posttreatment TGs, mimicking the real data set.

RESULTS: The different investigators in the group focused on the statistical challenges unique to family-based association analyses of phenotypes measured longitudinally and applied a wide spectrum of statistical methods such as linear mixed models, generalized estimating equations, and quasi-likelihood-based regression models. This article discusses the varying strategies explored by the group's investigators with the common goal of improving the power to detect association with repeated measures of a phenotype.

CONCLUSIONS: Although it is difficult to identify a common message emanating from the different contributions because of the diversity in the issues addressed, the unifying theme of the contributions lie in the search for novel analytic strategies to circumvent the limitations of existing methodologies to detect genetic association.}, } @article {pmid30255814, year = {2018}, author = {Wang, X and Boekstegers, F and Brinster, R}, title = {Methods and results from the genome-wide association group at GAW20.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {79}, pmid = {30255814}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: This paper summarizes the contributions from the Genome-wide Association Study group (GWAS group) of the GAW20. The GWAS group contributions focused on topics such as association tests, phenotype imputation, and application of empirical kinships. The goals of the GWAS group contributions were varied. A real or a simulated data set based on the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study was employed by different methods. Different outcomes and covariates were considered, and quality control procedures varied throughout the contributions.

RESULTS: The consideration of heritability and family structure played a major role in some contributions. The inclusion of family information and adaptive weights based on data were found to improve power in genome-wide association studies. It was proven that gene-level approaches are more powerful than single-marker analysis. Other contributions focused on the comparison between pedigree-based kinship and empirical kinship matrices, and investigated similar results in heritability estimation, association mapping, and genomic prediction. A new approach for linkage mapping of triglyceride levels was able to identify a novel linkage signal.

CONCLUSIONS: This summary paper reports on promising statistical approaches and findings of the members of the GWAS group applied on real and simulated data which encompass the current topics of epigenetic and pharmacogenomics.}, } @article {pmid30255799, year = {2018}, author = {Armañanzas, R}, title = {Revealing post-transcriptional microRNA-mRNA regulations in Alzheimer's disease through ensemble graphs.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {668}, pmid = {30255799}, issn = {1471-2164}, mesh = {Alzheimer Disease/*genetics/metabolism ; Bayes Theorem ; Case-Control Studies ; Female ; Gene Expression Profiling ; *Gene Regulatory Networks ; Humans ; Male ; MicroRNAs/*genetics ; Middle Aged ; Models, Biological ; *RNA Processing, Post-Transcriptional ; RNA, Messenger/genetics/*metabolism ; }, abstract = {BACKGROUND: In silico investigations on the integration of multiple datasets are in need of higher statistical power methods to unveil secondary findings that were hidden from the initial analyses. We present here a novel method for the network analysis of messenger RNA post-translational regulation by microRNA molecules. The method integrates expression data and sequence binding predictions through a set of sound machine learning techniques, forwarding all results to an ensemble graph of regulations.

RESULTS: Bayesian network classifiers are induced based on a pool of ensemble graphs with ascending order of complexity. Individual goodness-of-fit and classification performances are evaluated for each learned model. As a testbed, four Alzheimer's disease datasets are integrated using the new approach, achieving top values of 0.9794 ± 0.01 for the area under the receiver operating characteristic curve and 0.9439 ± 0.0234 for the prediction accuracy.

CONCLUSIONS: Post-transcriptional regulations found by the optimal network classifier concur with previous literature findings. Furthermore, additional network structures suggest previously unreported regulations in the state of the art of Alzheimer's research. The quantitative performance as well as sound biological findings provide confidence in the ensemble approach and encourage similar integrative analyses for other conditions.}, } @article {pmid30255791, year = {2018}, author = {Qiao, W and Akhter, N and Fang, X and Maximova, T and Plaku, E and Shehu, A}, title = {From mutations to mechanisms and dysfunction via computation and mining of protein energy landscapes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {671}, pmid = {30255791}, issn = {1471-2164}, mesh = {*Algorithms ; Computational Biology/methods ; Humans ; *Models, Molecular ; *Mutation ; Protein Conformation ; Proteins/chemistry/*genetics/*metabolism ; Thermodynamics ; }, abstract = {BACKGROUND: The protein energy landscape underscores the inherent nature of proteins as dynamic molecules interconverting between structures with varying energies. Reconstructing a protein's energy landscape holds the key to characterizing a protein's equilibrium conformational dynamics and its relationship to function. Many pathogenic mutations in protein sequences alter the equilibrium dynamics that regulates molecular interactions and thus protein function. In principle, reconstructing energy landscapes of a protein's healthy and diseased variants is a central step to understanding how mutations impact dynamics, biological mechanisms, and function.

RESULTS: Recent computational advances are yielding detailed, sample-based representations of protein energy landscapes. In this paper, we propose and describe two novel methods that leverage computed, sample-based representations of landscapes to reconstruct them and extract from them informative local structures that reveal the underlying organization of an energy landscape. Such structures constitute landscape features that, as we demonstrate here, can be utilized to detect alterations of landscapes upon mutation.

CONCLUSIONS: The proposed methods detect altered protein energy landscape features in response to sequence mutations. By doing so, the methods allow formulating hypotheses on the impact of mutations on specific biological activities of a protein. This work demonstrates that the availability of energy landscapes of healthy and diseased variants of a protein opens up new avenues to harness the quantitative information embedded in landscapes to summarize mechanisms via which mutations alter protein dynamics to percolate to dysfunction.}, } @article {pmid30255788, year = {2018}, author = {Yang, R and Zhu, D}, title = {A graph-based filtering method for top-down mass spectral identification.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {666}, pmid = {30255788}, issn = {1471-2164}, mesh = {*Algorithms ; *Computer Graphics ; Databases, Protein ; Escherichia coli/*metabolism ; Escherichia coli Proteins/*analysis ; Protein Processing, Post-Translational ; Proteome/*analysis ; Sequence Analysis, Protein/methods ; Tandem Mass Spectrometry/*methods ; }, abstract = {BACKGROUND: Database search has been the main approach for proteoform identification by top-down tandem mass spectrometry. However, when the target proteoform that produced the spectrum contains post-translational modifications (PTMs) and/or mutations, it is quite time consuming to align a query spectrum against all protein sequences without any PTMs and mutations in a large database. Consequently, it is essential to develop efficient and sensitive filtering algorithms for speeding up database search.

RESULTS: In this paper, we propose a spectrum graph matching (SGM) based protein sequence filtering method for top-down mass spectral identification. It uses the subspectra of a query spectrum to generate spectrum graphs and searches them against a protein database to report the best candidates. As the sequence tag and gaped tag approaches need the preprocessing step to extract and select tags, the SGM filtering method circumvents this preprocessing step, thus simplifying data processing. We evaluated the filtration efficiency of the SGM filtering method with various parameter settings on an Escherichia coli top-down mass spectrometry data set and compared the performances of the SGM filtering method and two tag-based filtering methods on a data set of MCF-7 cells.

CONCLUSIONS: Experimental results on the data sets show that the SGM filtering method achieves high sensitivity in protein sequence filtration. When coupled with a spectral alignment algorithm, the SGM filtering method significantly increases the number of identified proteoform spectrum-matches compared with the tag-based methods in top-down mass spectrometry data analysis.}, } @article {pmid30255786, year = {2018}, author = {Han, Y and He, F and Chen, Y and Liu, Y and Yu, H}, title = {SiRNA silencing efficacy prediction based on a deep architecture.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {669}, pmid = {30255786}, issn = {1471-2164}, mesh = {*Algorithms ; Computational Biology/*methods ; *Gene Silencing ; Gene Targeting/*methods ; Humans ; Machine Learning ; *Neural Networks (Computer) ; RNA, Messenger/genetics ; RNA, Small Interfering/chemistry/*genetics ; }, abstract = {BACKGROUND: Small interfering RNA (siRNA) can be used to post-transcriptional gene regulation by knocking down targeted genes. In functional genomics, biomedical research and cancer therapeutics, siRNA design is a critical research topic. Various computational algorithms have been developed to select the most effective siRNA, whereas the efficacy prediction accuracy is not so satisfactory. Many existing computational methods are based on feature engineering, which may lead to biased and incomplete features. Deep learning utilizes non-linear mapping operations to detect potential feature pattern and has been considered perform better than existing machine learning method.

RESULTS: In this paper, to further improve the prediction accuracy and facilitate gene functional studies, we developed a new powerful siRNA efficacy predictor based on a deep architecture. First, we extracted hidden feature patterns from two modalities, including sequence context features and thermodynamic property. Then, we constructed a deep architecture to implement the prediction. On the available largest siRNA database, the performance of our proposed method was measured with 0.725 PCC and 0.903 AUC value. The comparative experiment showed that our proposed architecture outperformed several siRNA prediction methods.

CONCLUSIONS: The results demonstrate that our deep architecture is stable and efficient to predict siRNA silencing efficacy. The method could help select candidate siRNA for targeted mRNA, and further promote the development of RNA interference.}, } @article {pmid30255785, year = {2018}, author = {Xie, L and He, S and Song, X and Bo, X and Zhang, Z}, title = {Deep learning-based transcriptome data classification for drug-target interaction prediction.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {667}, pmid = {30255785}, issn = {1471-2164}, mesh = {*Algorithms ; Computer Simulation ; Databases, Factual ; Drug Discovery ; *Drug Interactions ; Gene Expression Profiling/*methods ; Humans ; *Machine Learning ; Models, Theoretical ; Molecular Targeted Therapy ; Proteins/genetics/*metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: The ability to predict the interaction of drugs with target proteins is essential to research and development of drug. However, the traditional experimental paradigm is costly, and previous in silico prediction paradigms have been impeded by the wide range of data platforms and data scarcity.

RESULTS: In this paper, we modeled the prediction of drug-target interactions as a binary classification task. Using transcriptome data from the L1000 database of the LINCS project, we developed a framework based on a deep-learning algorithm to predict potential drug target interactions. Once fully trained, the model achieved over 98% training accuracy. The results of our research demonstrated that our framework could discover more reliable DTIs than found by other methods. This conclusion was validated further across platforms with a high percentage of overlapping interactions.

CONCLUSIONS: Our model's capacity of integrating transcriptome data from drugs and genes strongly suggests the strength of its potential for DTI prediction, thereby improving the drug discovery process.}, } @article {pmid30255784, year = {2018}, author = {Beltran, JA and Aguilera-Mendoza, L and Brizuela, CA}, title = {Optimal selection of molecular descriptors for antimicrobial peptides classification: an evolutionary feature weighting approach.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {672}, pmid = {30255784}, issn = {1471-2164}, mesh = {*Algorithms ; Anti-Infective Agents/chemistry/*classification/pharmacology ; Antimicrobial Cationic Peptides/chemistry/*classification/pharmacology ; Bacteria/*drug effects ; Computer Simulation ; *Evolution, Molecular ; Models, Molecular ; *Pattern Recognition, Automated ; Quantitative Structure-Activity Relationship ; }, abstract = {BACKGROUND: Antimicrobial peptides are a promising alternative for combating pathogens resistant to conventional antibiotics. Computer-assisted peptide discovery strategies are necessary to automatically assess a significant amount of data by generating models that efficiently classify what an antimicrobial peptide is, before its evaluation in the wet lab. Model's performance depends on the selection of molecular descriptors for which an efficient and effective approach has recently been proposed. Unfortunately, how to adapt this method to the selection of molecular descriptors for the classification of antimicrobial peptides and the performance it can achieve, have only preliminary been explored.

RESULTS: We propose an adaptation of this successful feature selection approach for the weighting of molecular descriptors and assess its performance. The evaluation is conducted on six high-quality benchmark datasets that have previously been used for the empirical evaluation of state-of-art antimicrobial prediction tools in an unbiased manner. The results indicate that our approach substantially reduces the number of required molecular descriptors, improving, at the same time, the performance of classification with respect to using all molecular descriptors. Our models also outperform state-of-art prediction tools for the classification of antimicrobial and antibacterial peptides.

CONCLUSIONS: The proposed methodology is an efficient approach for the development of models to classify antimicrobial peptides. Particularly in the generation of models for discrimination against a specific antimicrobial activity, such as antibacterial. One of our future directions is aimed at using the obtained classifier to search for antimicrobial peptides in various transcriptomes.}, } @article {pmid30255782, year = {2018}, author = {Hakguder, Z and Shu, J and Liao, C and Pan, K and Cui, J}, title = {Genome-scale MicroRNA target prediction through clustering with Dirichlet process mixture model.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {658}, pmid = {30255782}, issn = {1471-2164}, support = {P20 GM104320/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Bayes Theorem ; Binding Sites ; Computational Biology ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; *Genome, Human ; Humans ; Machine Learning ; MicroRNAs/*genetics ; Neoplasms/*genetics/metabolism/pathology ; RNA, Messenger/genetics/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: MicroRNA regulation is fundamentally responsible for fine-tuning the whole gene network in human and has been implicated in most physiological and pathological conditions. Studying regulatory impact of microRNA on various cellular and disease processes has resulted in numerous computational tools that investigate microRNA-mRNA interactions through the prediction of static binding site highly dependent on sequence pairing. However, what hindered the practical use of such target prediction is the interplay between competing and cooperative microRNA binding that complicates the whole regulatory process exceptionally.

RESULTS: We developed a new method for improved microRNA target prediction based on Dirichlet Process Gaussian Mixture Model (DPGMM) using a large collection of molecular features associated with microRNA, mRNA, and the interaction sites. Multiple validations based on microRNA-mRNA interactions reported in recent large-scale sequencing analyses and a screening test on the entire human transcriptome show that our model outperformed several state-of-the-art tools in terms of promising predictive power on binding sites specific to transcript isoforms with reduced false positive prediction. Last, we illustrated the use of predicted targets in constructing conditional microRNA-mediated gene regulation networks in human cancer.

CONCLUSION: The probability-based binding site prediction provides not only a useful tool for differentiating microRNA targets according to the estimated binding potential but also a capability highly important for exploring dynamic regulation where binding competition is involved.}, } @article {pmid30255780, year = {2018}, author = {Zhu, Y and Li, Y and Liu, J and Qin, L and Yu, JX}, title = {Discovering large conserved functional components in global network alignment by graph matching.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 7}, pages = {670}, pmid = {30255780}, issn = {1471-2164}, mesh = {*Algorithms ; Animals ; Computational Biology/*methods ; Computer Graphics ; Gene Ontology ; *Gene Regulatory Networks ; Humans ; Models, Theoretical ; *Protein Interaction Mapping ; Proteins/genetics/*metabolism ; }, abstract = {BACKGROUND: Aligning protein-protein interaction (PPI) networks is very important to discover the functionally conserved sub-structures between different species. In recent years, the global PPI network alignment problem has been extensively studied aiming at finding the one-to-one alignment with the maximum matching score. However, finding large conserved components remains challenging due to its NP-hardness.

RESULTS: We propose a new graph matching method GMAlign for global PPI network alignment. It first selects some pairs of important proteins as seeds, followed by a gradual expansion to obtain an initial matching, and then it refines the current result to obtain an optimal alignment result iteratively based on the vertex cover. We compare GMAlign with the state-of-the-art methods on the PPI network pairs obtained from the largest BioGRID dataset and validate its performance. The results show that our algorithm can produce larger size of alignment, and can find bigger and denser common connected subgraphs as well for the first time. Meanwhile, GMAlign can achieve high quality biological results, as measured by functional consistency and semantic similarity of the Gene Ontology terms. Moreover, we also show that GMAlign can achieve better results which are structurally and biologically meaningful in the detection of large conserved biological pathways between species.

CONCLUSIONS: GMAlign is a novel global network alignment tool to discover large conserved functional components between PPI networks. It also has many potential biological applications such as conserved pathway and protein complex discovery across species. The GMAlign software and datasets are avaialbile at https://github.com/yzlwhu/GMAlign .}, } @article {pmid30255779, year = {2018}, author = {Auerbach, J and Howey, R and Jiang, L and Justice, A and Li, L and Oualkacha, K and Sayols-Baixeras, S and Aslibekyan, SW}, title = {Causal modeling in a multi-omic setting: insights from GAW20.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {74}, pmid = {30255779}, issn = {1471-2156}, support = {K01 HL136700/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Increasingly available multilayered omics data on large populations has opened exciting analytic opportunities and posed unique challenges to robust estimation of causal effects in the setting of complex disease phenotypes. The GAW20 Causal Modeling Working Group has applied complementary approaches (eg, Mendelian randomization, structural equations modeling, Bayesian networks) to discover novel causal effects of genomic and epigenomic variation on lipid phenotypes, as well as to validate prior findings from observational studies.

RESULTS: Two Mendelian randomization studies have applied novel approaches to instrumental variable selection in methylation data, identifying bidirectional causal effects of CPT1A and triglycerides, as well as of RNMT and C6orf42, on high-density lipoprotein cholesterol response to fenofibrate. The CPT1A finding also emerged in a Bayesian network study. The Mendelian randomization studies have implemented both existing and novel steps to account for pleiotropic effects, which were independently detected in the GAW20 data via a structural equation modeling approach. Two studies estimated indirect effects of genomic variation (via DNA methylation and/or correlated phenotypes) on lipid outcomes of interest. Finally, a novel weighted R2 measure was proposed to complement other causal inference efforts by controlling for the influence of outlying observations.

CONCLUSIONS: The GAW20 contributions illustrate the diversity of possible approaches to causal inference in the multi-omic context, highlighting the promises and assumptions of each method and the benefits of integrating both across methods and across omics layers for the most robust and comprehensive insights into disease processes.}, } @article {pmid30255778, year = {2018}, author = {Nustad, HE and Almeida, M and Canty, AJ and LeBlanc, M and Page, CM and Melton, PE}, title = {Epigenetics, heritability and longitudinal analysis.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {77}, pmid = {30255778}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Longitudinal data and repeated measurements in epigenome-wide association studies (EWAS) provide a rich resource for understanding epigenetics. We summarize 7 analytical approaches to the GAW20 data sets that addressed challenges and potential applications of phenotypic and epigenetic data. All contributions used the GAW20 real data set and employed either linear mixed effect (LME) models or marginal models through generalized estimating equations (GEE). These contributions were subdivided into 3 categories: (a) quality control (QC) methods for DNA methylation data; (b) heritability estimates pretreatment and posttreatment with fenofibrate; and (c) impact of drug response pretreatment and posttreatment with fenofibrate on DNA methylation and blood lipids.

RESULTS: Two contributions addressed QC and identified large statistical differences with pretreatment and posttreatment DNA methylation, possibly a result of batch effects. Two contributions compared epigenome-wide heritability estimates pretreatment and posttreatment, with one employing a Bayesian LME and the other using a variance-component LME. Density curves comparing these studies indicated these heritability estimates were similar. Another contribution used a variance-component LME to depict the proportion of heritability resulting from a genetic and shared environment. By including environmental exposures as random effects, the authors found heritability estimates became more stable but not significantly different. Two contributions investigated treatment response. One estimated drug-associated methylation effects on triglyceride levels as the response, and identified 11 significant cytosine-phosphate-guanine (CpG) sites with or without adjusting for high-density lipoprotein. The second contribution performed weighted gene coexpression network analysis and identified 6 significant modules of at least 30 CpG sites, including 3 modules with topological differences pretreatment and posttreatment.

CONCLUSIONS: Four conclusions from this GAW20 working group are: (a) QC measures are an important consideration for EWAS studies that are investigating multiple time points or repeated measurements; (b) application of heritability estimates between time points for individual CpG sites is a useful QC measure for DNA methylation studies; (c) drug intervention demonstrated strong epigenome-wide DNA methylation patterns across the 2 time points; and (d) new statistical methods are required to account for the environmental contributions of DNA methylation across time. These contributions demonstrate numerous opportunities exist for the analysis of longitudinal data in future epigenetic studies.}, } @article {pmid30255777, year = {2018}, author = {Fuady, AM and Lent, S and Sarnowski, C and Tintle, NL}, title = {Application of novel and existing methods to identify genes with evidence of epigenetic association: results from GAW20.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {72}, pmid = {30255777}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; R15 HG006915/HG/NHGRI NIH HHS/United States ; T32 GM074905/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: The rise in popularity and accessibility of DNA methylation data to evaluate epigenetic associations with disease has led to numerous methodological questions. As part of GAW20, our working group of 8 research groups focused on gene searching methods.

RESULTS: Although the methods were varied, we identified 3 main themes within our group. First, many groups tackled the question of how best to use pedigree information in downstream analyses, finding that (a) the use of kinship matrices is common practice, (b) ascertainment corrections may be necessary, and (c) pedigree information may be useful for identifying parent-of-origin effects. Second, many groups also considered multimarker versus single-marker tests. Multimarker tests had modestly improved power versus single-marker methods on simulated data, and on real data identified additional associations that were not identified with single-marker methods, including identification of a gene with a strong biological interpretation. Finally, some of the groups explored methods to combine single-nucleotide polymorphism (SNP) and DNA methylation into a single association analysis.

CONCLUSIONS: A causal inference method showed promise at discovering new mechanisms of SNP activity; gene-based methods of summarizing SNP and DNA methylation data also showed promise. Even though numerous questions still remain in the analysis of DNA methylation data, our discussions at GAW20 suggest some emerging best practices.}, } @article {pmid30255776, year = {2018}, author = {Wei, R and Wu, Y}, title = {Modification effect of fenofibrate therapy, a longitudinal epigenomic-wide methylation study of triglycerides levels in the GOLDN study.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {75}, pmid = {30255776}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Identification of interactions between epigenetic factors and treatments might lead to personalized intervention of diseases. This paper aims to examine the modification effect of fenofibrate therapy on the association of methylation levels and fasting blood triglycerides (TG), and the related biological pathways among methylation sites.

RESULTS: Mixed-effects models were employed to assess pre- and posttreatment associations and drug modification effects simultaneously. Five cytosine-phosphate-guanine (CpG) sites were found to be associated with TG levels before and after the fenofibrate therapy: cg00574958, cg17058475, and cg01082498 on CPT1A gene, chromosome 11; cg03725309 on SARS, chromosome 1; and cg06500161 on ABCG1, chromosome 21. In addition, fenofibrate therapy modified the methylation levels on the following 4 CpG sites: cg20015535 (gene EGLN1, chromosome 1); cg24870738 (gene RNF220, chromosome 1); cg06891775 (gene LOC283050, chromosome 10); and cg00607630 (gene USP7, chromosome 16). Further, gene set enrichment analysis (GSEA) identified cancer- and metabolism-related pathways that were associated with TG-related CpG sites.

CONCLUSIONS: We identified modification effects of fenofibrate on the associations between blood TG levels and several CpG sites. Pathway enrichment analysis indicated the alternations in some metabolism and cancer-related pathways. Our findings have important implications for future research in pharmacoepigenetics and personalized medicine.}, } @article {pmid30255775, year = {2018}, author = {Lent, S and Xu, H and Wang, L and Wang, Z and Sarnowski, C and Hivert, MF and Dupuis, J}, title = {Comparison of novel and existing methods for detecting differentially methylated regions.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {84}, pmid = {30255775}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; T32 GM074905/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Single-probe analyses in epigenome-wide association studies (EWAS) have identified associations between DNA methylation and many phenotypes, but do not take into account information from neighboring probes. Methods to detect differentially methylated regions (DMRs) (clusters of neighboring probes associated with a phenotype) may provide more power to detect associations between DNA methylation and diseases or phenotypes of interest.

RESULTS: We proposed a novel approach, GlobalP, and perform comparisons with 3 methods-DMRcate, Bumphunter, and comb-p-to identify DMRs associated with log triglycerides (TGs) in real GAW20 data before and after fenofibrate treatment. We applied these methods to the summary statistics from an EWAS performed on the methylation data. Comb-p, DMRcate, and GlobalP detected very similar DMRs near the gene CPT1A on chromosome 11 in both the pre- and posttreatment data. In addition, GlobalP detected 2 DMRs before fenofibrate treatment in the genes ETV6 and ABCG1. Bumphunter identified several DMRs on chromosomes 1 and 20, which did not overlap with DMRs detected by other methods.

CONCLUSIONS: Our novel method detected the same DMR identified by two existing methods and detected two additional DMRs not identified by any of the existing methods we compared.}, } @article {pmid30255774, year = {2018}, author = {Darst, B and Engelman, CD and Tian, Y and Lorenzo Bermejo, J}, title = {Data mining and machine learning approaches for the integration of genome-wide association and methylation data: methodology and main conclusions from GAW20.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {76}, pmid = {30255774}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Multiple layers of genetic and epigenetic variability are being simultaneously explored in an increasing number of health studies. We summarize here different approaches applied in the Data Mining and Machine Learning group at the GAW20 to integrate genome-wide genotype and methylation array data.

RESULTS: We provide a non-intimidating introduction to some frequently used methods to investigate high-dimensional molecular data and compare the different approaches tried by group members: random forest, deep learning, cluster analysis, mixed models, and gene-set enrichment analysis. Group contributions were quite heterogeneous regarding investigated data sets (real vs simulated), conducted data quality control and assessed phenotypes (eg, metabolic syndrome vs relative differences of log-transformed triglyceride concentrations before and after fenofibrate treatment). However, some common technical issues were detected, leading to practical recommendations.

CONCLUSIONS: Different sources of correlation were identified by group members, including population stratification, family structure, batch effects, linkage disequilibrium and correlation of methylation values at neighboring cytosine-phosphate-guanine (CpG) sites, and the majority of applied approaches were able to take into account identified correlation structures. The ability to efficiently deal with high-dimensional omics data, and the model free nature of the approaches that did not require detailed model specifications were clearly recognized as the main strengths of applied methods. A limitation of random forest is its sensitivity to highly correlated variables. The parameter setup and the interpretation of results from deep learning methods, in particular deep neural networks, can be extremely challenging. Cluster analysis and mixed models may need some predimension reduction based on existing literature, data filtering, and supplementary statistical methods, and gene-set enrichment analysis requires biological insight.}, } @article {pmid30255773, year = {2018}, author = {Xia, X and Weng, H and Men, R and Sun, R and Zee, BCY and Chong, KC and Wang, MH}, title = {Incorporating methylation genome information improves prediction accuracy for drug treatment responses.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {78}, pmid = {30255773}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: An accumulation of evidence has revealed the important role of epigenetic factors in explaining the etiopathogenesis of human diseases. Several empirical studies have successfully incorporated methylation data into models for disease prediction. However, it is still a challenge to integrate different types of omics data into prediction models, and the contribution of methylation information to prediction remains to be fully clarified.

RESULTS: A stratified drug-response prediction model was built based on an artificial neural network to predict the change in the circulating triglyceride level after fenofibrate intervention. Associated single-nucleotide polymorphisms (SNPs), methylation of selected cytosine-phosphate-guanine (CpG) sites, age, sex, and smoking status, were included as predictors. The model with selected SNPs achieved a mean 5-fold cross-validation prediction error rate of 43.65%. After adding methylation information into the model, the error rate dropped to 41.92%. The combination of significant SNPs, CpG sites, age, sex, and smoking status, achieved the lowest prediction error rate of 41.54%.

CONCLUSIONS: Compared to using SNP data only, adding methylation data in prediction models slightly improved the error rate; further prediction error reduction is achieved by a combination of genome, methylation genome, and environmental factors.}, } @article {pmid30255772, year = {2018}, author = {Fernández-Rhodes, L and Howard, AG and Tao, R and Young, KL and Graff, M and Aiello, AE and North, KE and Justice, AE}, title = {Characterization of the contribution of shared environmental and genetic factors to metabolic syndrome methylation heritability and familial correlations.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {69}, pmid = {30255772}, issn = {1471-2156}, support = {K99 HL130580/HL/NHLBI NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; KL2 TR001109/TR/NCATS NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; T32 HD007168/HD/NICHD NIH HHS/United States ; P2C HD050924/HD/NICHD NIH HHS/United States ; T32 HL007055/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: Transgenerational epigenetic inheritance has been posited as a possible contributor to the observed heritability of metabolic syndrome (MetS). Yet the extent to which estimates of epigenetic inheritance for DNA methylation sites are inflated by environmental and genetic covariance within families is still unclear. We applied current methods to quantify the environmental and genetic contributors to the observed heritability and familial correlations of four previously associated MetS methylation sites at three genes (CPT1A, SOCS3 and ABCG1) using real data made available through the GAW20.

RESULTS: Our findings support the role of both shared environment and genetic variation in explaining the heritability of MetS and the four MetS cytosine-phosphate-guanine (CpG) sites, although the resulting heritability estimates were indistinguishable from one another. Familial correlations by type of relative pair generally followed our expectation based on relatedness, but in the case of sister and parent pairs we observed nonsignificant trends toward greater correlation than expected, as would be consistent with the role of shared environmental factors in the inflation of our estimated correlations.

CONCLUSIONS: Our work provides an interesting and flexible statistical framework for testing models of epigenetic inheritance in the context of human family studies. Future work should endeavor to replicate our findings and advance these methods to more robustly describe epigenetic inheritance patterns in human populations.}, } @article {pmid30255771, year = {2018}, author = {Sarnowski, C and Lent, S and Dupuis, J}, title = {Investigation of parent-of-origin effects induced by fenofibrate treatment on triglycerides levels.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {83}, pmid = {30255771}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Genome-wide association studies performed on triglycerides (TGs) have not accounted for epigenetic mechanisms that may partially explain trait heritability.

RESULTS: Parent-of-origin (POO) effect association analyses using an agnostic approach or a candidate approach were performed for pretreatment TG levels, posttreatment TG levels, and pre- and posttreatment TG-level differences in the real GAW20 family data set. We detected 22 genetic variants with suggestive POO effects with at least 1 phenotype (P ≤ 10- 5). We evaluated the association of these 22 significant genetic variants showing POO effects with close DNA methylation probes associated with TGs. A total of 18 DNA methylation probes located in the vicinity of the 22 SNPs were associated with at least 1 phenotype and 6 SNP-probe pairs were associated with DNA methylation probes at the nominal level of P < 0.05, among which 1 pair presented evidence of POO effect. Our analyses identified a paternal effect of SNP rs301621 on the difference between pre- and posttreatment TG levels (P = 1.2 × 10- 5). This same SNP showed evidence for a maternal effect on methylation levels of a nearby probe (cg10206250; P = 0.01). Using a causal inference test we established that the observed POO effect of rs301621 was not mediated by DNA methylation at cg10206250.

CONCLUSIONS: We performed POO effect association analyses of SNPs with TGs, as well as association analyses of SNPs with DNA methylation probes. These analyses, which were followed by a causal inference test, established that the paternal effect at the SNP rs301621 is induced by treatment and is not mediated by methylation level at cg10206250.}, } @article {pmid30255770, year = {2018}, author = {Park, JY and Wu, C and Pan, W}, title = {An adaptive gene-level association test for pedigree data.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {68}, pmid = {30255770}, issn = {1471-2156}, support = {R21 AG057038/AG/NIA NIH HHS/United States ; R01 GM113250/GM/NIGMS NIH HHS/United States ; R01 HL105397/HL/NHLBI NIH HHS/United States ; R01 HL116720/HL/NHLBI NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: We propose a gene-level association test that accounts for individual relatedness and population structures in pedigree data in the framework of linear mixed models (LMMs). Our method data-adaptively combines the results across a class of score-based tests, only requiring fitting a single null model (under the null hypothesis) for the whole genome, thereby being computationally efficient.

RESULTS: We applied our approach to test for association with the high-density lipoprotein (HDL) ratio of post- and pretreatments in GAW20 data. Using the LMM similar to that used by Aslibekyan et al. (PLos One, 7:48663, 2012), our method identified 2 nearly significant genes (APOA5 and ZNF259) near rs964184, whereas neither the other gene-level tests nor the standard test on each individual single-nucleotide polymorphism (SNP) detected any significant gene in a genome-wide scan.

CONCLUSIONS: Gene-level association testing can be a complementary approach to the SNP-level association testing and our method is adaptive and efficient compared to several other existing gene-level association tests.}, } @article {pmid30255769, year = {2018}, author = {Shen, X and Lu, Q}, title = {Joint analysis of genetic and epigenetic data using a conditional autoregressive model.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {71}, pmid = {30255769}, issn = {1471-2156}, support = {R01 DA043501/DA/NIDA NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; R01 LM012848/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Rapidly evolving high-throughput technology has made it cost-effective to collect multilevel omic data in clinical and biological studies. Different types of omic data collected from these studies provide both shared and complementary information, and can be integrated into association analysis to enhance the power of identifying novel disease-associated biomarkers. To model the joint effect of genetic markers and DNA methylation on the phenotype of interest, we propose a joint conditional autoregressive (JCAR) model. A linear score test is used for hypothesis testing and the corresponding p value can be obtained using the Davies method.

RESULTS: The JCAR model was applied to the GAW20 data from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) study. In our application of the JCAR model, we consider a baseline model and a full model. In the baseline model, we consider 3 different scenarios: a model with only genetic information, a model with only DNA methylation information at visit 2, and a model using both genetic and DNA methylation information at visit 2. For the full model, we consider both genetic and DNA methylation information at visit 2 and visit 4. The top 10 significant genes are reported for each model. Based on the results, we found that the gene MYO3B was significant as long as the methylation information was considered in the analysis.

CONCLUSIONS: JCAR is a useful tool for joint association analysis of genetic and epigenetic data. It is easy to implement and is computationally efficient. It can also be extended to analyze other types of omic data.}, } @article {pmid30255768, year = {2018}, author = {Li, L and Wang, C and Lu, T and Lin, S and Hu, YQ}, title = {Indirect effect inference and application to GAW20 data.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {67}, pmid = {30255768}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Association studies using a single type of omics data have been successful in identifying disease-associated genetic markers, but the underlying mechanisms are unaddressed. To provide a possible explanation of how these genetic factors affect the disease phenotype, integration of multiple omics data is needed.

RESULTS: We propose a novel method, LIPID (likelihood inference proposal for indirect estimation), that uses both single nucleotide polymorphism (SNP) and DNA methylation data jointly to analyze the association between a trait and SNPs. The total effect of SNPs is decomposed into direct and indirect effects, where the indirect effects are the focus of our investigation. Simulation studies show that LIPID performs better in various scenarios than existing methods. Application to the GAW20 data also leads to encouraging results, as the genes identified appear to be biologically relevant to the phenotype studied.

CONCLUSIONS: The proposed LIPID method is shown to be meritorious in extensive simulations and in real-data analyses.}, } @article {pmid30255767, year = {2018}, author = {Strickland, JC and Chen, IC and Wang, C and Fardo, DW}, title = {Longitudinal data methods for evaluating genome-by-epigenome interactions in families.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {82}, pmid = {30255767}, issn = {1471-2156}, support = {K25 AG043546/AG/NIA NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; R01 HL104135/HL/NHLBI NIH HHS/United States ; U01 HL072524/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: Longitudinal measurement is commonly employed in health research and provides numerous benefits for understanding disease and trait progression over time. More broadly, it allows for proper treatment of correlated responses within clusters. We evaluated 3 methods for analyzing genome-by-epigenome interactions with longitudinal outcomes from family data.

RESULTS: Linear mixed-effect models, generalized estimating equations, and quadratic inference functions were used to test a pharmacoepigenetic effect in 200 simulated posttreatment replicates. Adjustment for baseline outcome provided greater power and more accurate control of Type I error rates than computation of a pre-to-post change score.

CONCLUSIONS: Comparison of all modeling approaches indicated a need for bias correction in marginal models and similar power for each method, with quadratic inference functions providing a minor decrement in power compared to generalized estimating equations and linear mixed-effects models.}, } @article {pmid30255766, year = {2018}, author = {LeBlanc, M and Nustad, HE and Zucknick, M and Page, CM}, title = {Quality control for Illumina 450K methylation data in the absence of iDat files using correlation structure in pedigrees and repeated measures.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {66}, pmid = {30255766}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: An important feature in many genomic studies is quality control and normalization. This is particularly important when analyzing epigenetic data, where the process of obtaining measurements can be bias prone. The GAW20 data was from the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN), a study with multigeneration families, where DNA cytosine-phosphate-guanine (CpG) methylation was measured pre- and posttreatment with fenofibrate. We performed quality control assessment of the GAW20 DNA methylation data, including normalization, assessment of batch effects and detection of sample swaps.

RESULTS: We show that even after normalization, the GOLDN methylation data has systematic differences pre- and posttreatment. Through investigation of (a) CpGs sites containing a single nucleotide polymorphism, (b) the stability of breeding values for methylation across time points, and (c) autosomal gender-associated CpGs, 13 sample swaps were detected, 11 of which were posttreatment.

CONCLUSIONS: This paper demonstrates several ways to perform quality control of methylation data in the absence of raw data files and highlights the importance of normalization and quality control of the GAW20 methylation data from the GOLDN study.}, } @article {pmid30255765, year = {2018}, author = {Fisher, VA and Wang, L and Deng, X and Sarnowski, C and Cupples, LA and Liu, CT}, title = {Do changes in DNA methylation mediate or interact with SNP variation? A pharmacoepigenetic analysis.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {70}, pmid = {30255765}, issn = {1471-2156}, support = {R01 GM031575/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: In studies with multi-omics data available, there is an opportunity to investigate interdependent mechanisms of biological causality. The GAW20 data set includes both DNA genotype and methylation measures before and after fenofibrate treatment. Using change in triglyceride (TG) levels pre- to posttreatment as outcome, we present a mediation analysis that incorporates methylation. This approach allows us to simultaneously consider a mediation hypothesis that genotype affects change in TG level by means of its effect on methylation, and an interaction hypothesis that the effect of change in methylation on change in TG levels differs by genotype. We select 322 single-nucleotide polymorphism-cytosine-phosphate-guanine (SNP-CpG) site pairs for mediation analysis on the basis of proximity and marginal genome-wide association study (GWAS) and epigenome-wide association study (EWAS) significance, and present results from the real-data sample of 407 individuals with complete genotype, methylation, TG levels, and covariate data.

RESULTS: We identified 3 SNP-CpG site pairs with significant interaction effects at a Bonferroni-corrected significance threshold of 1.55E-4. None of the analyzed sites showed significant evidence of mediation. Power analysis by simulation showed that a sample size of at least 19,500 is needed to detect nominally significant indirect effects with true effect sizes equal to the point estimates at the locus with strongest evidence of mediation.

CONCLUSIONS: These results suggest that there is stronger evidence for interaction between genotype and methylation on change in triglycerides than for methylation mediating the effect of genotype.}, } @article {pmid30255764, year = {2018}, author = {Darst, BF and Malecki, KC and Engelman, CD}, title = {Using recursive feature elimination in random forest to account for correlated variables in high dimensional data.}, journal = {BMC genetics}, volume = {19}, number = {Suppl 1}, pages = {65}, pmid = {30255764}, issn = {1471-2156}, support = {P2C HD047873/HD/NICHD NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: Random forest (RF) is a machine-learning method that generally works well with high-dimensional problems and allows for nonlinear relationships between predictors; however, the presence of correlated predictors has been shown to impact its ability to identify strong predictors. The Random Forest-Recursive Feature Elimination algorithm (RF-RFE) mitigates this problem in smaller data sets, but this approach has not been tested in high-dimensional omics data sets.

RESULTS: We integrated 202,919 genotypes and 153,422 methylation sites in 680 individuals, and compared the abilities of RF and RF-RFE to detect simulated causal associations, which included simulated genotype-methylation interactions, between these variables and triglyceride levels. Results show that RF was able to identify strong causal variables with a few highly correlated variables, but it did not detect other causal variables.

CONCLUSIONS: Although RF-RFE decreased the importance of correlated variables, in the presence of many correlated variables, it also decreased the importance of causal variables, making both hard to detect. These findings suggest that RF-RFE may not scale to high-dimensional data.}, } @article {pmid30255564, year = {2019}, author = {Kong, L and Price, NM}, title = {Functional CTR-type Cu(I) transporters in an oceanic diatom.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {98-110}, doi = {10.1111/1462-2920.14428}, pmid = {30255564}, issn = {1462-2920}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Copper concentration is so low in some remote parts of the sea it limits phytoplankton growth, but may be high enough in coastal and estuarine regions to be toxic. Acclimation to variations in Cu concentration thus requires a tightly regulated Cu transport system to help maintain Cu homeostasis. In marine species, the molecular mechanisms of Cu transport are not known. We studied Cu-responsive genes and uptake in Thalassiosira oceanica at environmentally relevant Cu concentrations varying between 0.012 and 12 900 pmol Cu' l-1 . Copper uptake rate assessed at high Cu concentration was three-fold faster in Cu-limited than in Cu-replete cells, confirming the existence of an inducible uptake pathway in this diatom. Four putative CTR-type Cu transporters (ToCTR1, ToCTR2, ToCTR3a and ToCTR3b) identified in the transcriptome shared conserved features with known high-affinity Cu(I) transporters. Expression of the CTR genes was upregulated as Cu concentration declined and cells maintained maximum rates of growth. Further decreases in Cu led to decreased growth rate and increased abundance of ToCTR3a/b. Both ToCTR3a and 3b restored growth of a Cu transport mutant, Saccharomyces cerevisiae ctr1Δctr3Δ, in Cu-deficient medium and increased the uptake rates of Cu(I) and Cu(II). Thus, ToCTR3a/3b is a high-affinity Cu(I) transporter that, in conjunction with the other ToCTRs, may enable T. oceanica to survive in Cu-deplete ocean environments and respond to natural variation in Cu availability.}, } @article {pmid30255541, year = {2019}, author = {Cornejo-Castillo, FM and Muñoz-Marín, MDC and Turk-Kubo, KA and Royo-Llonch, M and Farnelid, H and Acinas, SG and Zehr, JP}, title = {UCYN-A3, a newly characterized open ocean sublineage of the symbiotic N2 -fixing cyanobacterium Candidatus Atelocyanobacterium thalassa.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {111-124}, doi = {10.1111/1462-2920.14429}, pmid = {30255541}, issn = {1462-2920}, support = {//Biosensomics to SGA (Convocatoria 2015 de ayudas Fundación BBVA a investigadores y creadores culturales)/ ; FPI (BES-2014-068285)//Consejo Superior de Investigaciones Científicas/ ; 493.01//Gordon and Betty Moore Foundation/ ; //Marie Curie International Outgoing Fellowship/ ; 329108//Simons Collaboration on Ocean Processes and Ecology (SCOPE)/ ; 545171//Simons Foundation/ ; //Spanish Ministry of Economy, Industry and Competitiveness/ ; VR 637-2013-7502//Svenska Forskningsrådet Formas/ ; }, abstract = {The symbiotic unicellular cyanobacterium Candidatus Atelocyanobacterium thalassa (UCYN-A) is one of the most abundant and widespread nitrogen (N2)-fixing cyanobacteria in the ocean. Although it remains uncultivated, multiple sublineages have been detected based on partial nitrogenase (nifH) gene sequences, including the four most commonly detected sublineages UCYN-A1, UCYN-A2, UCYN-A3 and UCYN-A4. However, very little is known about UCYN-A3 beyond the nifH sequences from nifH gene diversity surveys. In this study, single cell sorting, DNA sequencing, qPCR and CARD-FISH assays revealed discrepancies involving the identification of sublineages, which led to new information on the diversity of the UCYN-A symbiosis. 16S rRNA and nifH gene sequencing on single sorted cells allowed us to identify the 16S rRNA gene of the uncharacterized UCYN-A3 sublineage. We designed new CARD-FISH probes that allowed us to distinguish and observe UCYN-A2 in a coastal location (SIO Pier; San Diego) and UCYN-A3 in an open ocean location (Station ALOHA; Hawaii). Moreover, we reconstructed about 13% of the UCYN-A3 genome from Tara Oceans metagenomic data. Finally, our findings unveil the UCYN-A3 symbiosis in open ocean waters suggesting that the different UCYN-A sublineages are distributed along different size fractions of the plankton defined by the cell-size ranges of their prymnesiophyte hosts.}, } @article {pmid30254747, year = {2018}, author = {Basile, AJ and Schwartz, DB and Rigdon, J and Stapell, H}, title = {Status of evolutionary medicine within the field of nutrition and dietetics: A survey of professionals and students.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {201-210}, pmid = {30254747}, issn = {2050-6201}, abstract = {Lay Summary: Through an online survey of nutrition and dietetic professionals and students, we learned there is interest to incorporate evolutionary medicine into the nutrition and dietetics field and education programs.

Background and objectives: Evolutionary medicine is an emerging field that examines the evolutionary significance of modern disease to develop new preventative strategies or treatments. While many areas of interest in evolutionary medicine and public health involve diet, we currently lack an understanding of whether nutrition and dietetics professionals and students appreciate the potential of evolutionary medicine.

Methodology: Cross-sectional online survey to measure the level of appreciation, applicability and knowledge of evolutionary medicine among nutrition and dietetics professionals and students. We then examined the relationships between support of evolutionary medicine and (i) professionals and students, (ii) US region, (iii) religious belief and (iv) existing evolutionary knowledge.

Results: A total of 2039 people participated: students (n = 893) and professionals (n = 1146). The majority of the participants agree they are knowledgeable on the theory of evolution (59%), an understanding of evolution can aid the nutrition and dietetics field (58%), an evolutionary perspective would be beneficial in dietetics education (51%) and it is equally important to understand both the evolutionary and direct causes of disease (71%). Significant differences in responses between professionals and students suggest students are currently learning more about evolution and are also more supportive of using an evolutionary perspective. Whereas differences in responses by US region were minimal, differences by religious belief and prior evolutionary knowledge were significant; however, all responses were either neutral or supportive at varying strengths.

Conclusion and implications: There is interest among professionals and students to incorporate evolutionary medicine into the nutrition and dietetics field and education programs.}, } @article {pmid30254367, year = {2018}, author = {Du Toit, A}, title = {Folding unstable proteins.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {658}, doi = {10.1038/s41579-018-0092-2}, pmid = {30254367}, issn = {1740-1534}, } @article {pmid30254366, year = {2018}, author = {Du Toit, A}, title = {Increasing virulence factors.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {658}, doi = {10.1038/s41579-018-0091-3}, pmid = {30254366}, issn = {1740-1534}, } @article {pmid30254365, year = {2018}, author = {Du Toit, A}, title = {A class of its own.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {658}, doi = {10.1038/s41579-018-0090-4}, pmid = {30254365}, issn = {1740-1534}, } @article {pmid30254361, year = {2018}, author = {}, title = {The costs of climate inaction.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {433}, doi = {10.1038/d41586-018-06827-x}, pmid = {30254361}, issn = {1476-4687}, } @article {pmid30254360, year = {2018}, author = {}, title = {Discovery of Galileo's long-lost letter highlights the value of physical repositories.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {434}, doi = {10.1038/d41586-018-06825-z}, pmid = {30254360}, issn = {1476-4687}, } @article {pmid30254359, year = {2018}, author = {Baker, M}, title = {Cryo-electron microscopy shapes up.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {565-567}, doi = {10.1038/d41586-018-06791-6}, pmid = {30254359}, issn = {1476-4687}, } @article {pmid30254358, year = {2018}, author = {Kiser, GL}, title = {No more first authors, no more last authors.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {435}, doi = {10.1038/d41586-018-06779-2}, pmid = {30254358}, issn = {1476-4687}, } @article {pmid30254357, year = {2018}, author = {Comfort, N}, title = {Genetic determinism rides again.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {461-463}, doi = {10.1038/d41586-018-06784-5}, pmid = {30254357}, issn = {1476-4687}, } @article {pmid30254356, year = {2018}, author = {}, title = {Octopuses on ecstasy just want a cuddle.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {436}, doi = {10.1038/d41586-018-06746-x}, pmid = {30254356}, issn = {1476-4687}, } @article {pmid30254355, year = {2018}, author = {Maxmen, A}, title = {Discovery of vibrant deep-sea life prompts new worries over seabed mining.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {443-444}, doi = {10.1038/d41586-018-06771-w}, pmid = {30254355}, issn = {1476-4687}, } @article {pmid30254354, year = {2018}, author = {}, title = {How an atom forms a 'ghost' bond with a partner that isn't there.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {436}, doi = {10.1038/d41586-018-06745-y}, pmid = {30254354}, issn = {1476-4687}, } @article {pmid30254353, year = {2018}, author = {Abbott, A}, title = {Discovery of Galileo's long-lost letter shows he edited his heretical ideas to fool the Inquisition.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {441-442}, doi = {10.1038/d41586-018-06769-4}, pmid = {30254353}, issn = {1476-4687}, } @article {pmid30254352, year = {2018}, author = {}, title = {A daily aspirin might not be what the doctor ordered.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {437}, doi = {10.1038/d41586-018-06728-z}, pmid = {30254352}, issn = {1476-4687}, } @article {pmid30254351, year = {2018}, author = {}, title = {The multitasking cell that can build the parts of a human skeleton.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {437}, doi = {10.1038/d41586-018-06743-0}, pmid = {30254351}, issn = {1476-4687}, } @article {pmid30254350, year = {2018}, author = {Witze, A}, title = {Top US science agency unveils hotly anticipated harassment policy.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {444-445}, doi = {10.1038/d41586-018-06766-7}, pmid = {30254350}, issn = {1476-4687}, } @article {pmid30254349, year = {2018}, author = {Else, H}, title = {Prominent palaeontologist loses £1-million grant following bullying investigation.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {442-443}, doi = {10.1038/d41586-018-06764-9}, pmid = {30254349}, issn = {1476-4687}, mesh = {*Bullying ; *Research Support as Topic ; }, } @article {pmid30254348, year = {2018}, author = {Castelvecchi, D}, title = {Reimagining of Schrödinger's cat breaks quantum mechanics - and stumps physicists.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {446-447}, doi = {10.1038/d41586-018-06749-8}, pmid = {30254348}, issn = {1476-4687}, } @article {pmid30254347, year = {2018}, author = {Watson, T}, title = {Prehistoric children as young as eight worked as brickmakers and miners.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {445-446}, doi = {10.1038/d41586-018-06747-w}, pmid = {30254347}, issn = {1476-4687}, } @article {pmid30254346, year = {2018}, author = {}, title = {The exoplanet that could be Spock's home world.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {437}, doi = {10.1038/d41586-018-06725-2}, pmid = {30254346}, issn = {1476-4687}, } @article {pmid30254345, year = {2018}, author = {}, title = {Pathologists meet their match in tumour-spotting algorithm.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {436-437}, doi = {10.1038/d41586-018-06724-3}, pmid = {30254345}, issn = {1476-4687}, } @article {pmid30254344, year = {2018}, author = {}, title = {The devastating death toll forecast for Himalayan quakes.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {436}, doi = {10.1038/d41586-018-06702-9}, pmid = {30254344}, issn = {1476-4687}, } @article {pmid30254343, year = {2018}, author = {Samwer, M and Gerlich, DW}, title = {A core problem in nuclear assembly.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {467-468}, doi = {10.1038/d41586-018-06668-8}, pmid = {30254343}, issn = {1476-4687}, } @article {pmid30254342, year = {2018}, author = {Chica, RA}, title = {Designer proteins activate fluorescent molecules.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {471-472}, doi = {10.1038/d41586-018-06202-w}, pmid = {30254342}, issn = {1476-4687}, mesh = {Computational Biology ; *Fluorescence ; Proteins/*physiology ; }, } @article {pmid30254331, year = {2018}, author = {Chen, YX and Javid, B}, title = {More than merely drug resistance.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1078-1079}, doi = {10.1038/s41564-018-0250-3}, pmid = {30254331}, issn = {2058-5276}, } @article {pmid30254330, year = {2018}, author = {Martinez, J}, title = {Taming the beasts within.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1080-1081}, doi = {10.1038/s41564-018-0264-x}, pmid = {30254330}, issn = {2058-5276}, } @article {pmid30254329, year = {2018}, author = {}, title = {The importance of taking a break.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1077}, doi = {10.1038/s41564-018-0269-5}, pmid = {30254329}, issn = {2058-5276}, } @article {pmid30254328, year = {2018}, author = {Lee, B}, title = {Greasing the receptor.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1082-1083}, doi = {10.1038/s41564-018-0251-2}, pmid = {30254328}, issn = {2058-5276}, } @article {pmid30254178, year = {2018}, author = {Bayley, JS and Winther, CB and Andersen, MK and Grønkjær, C and Nielsen, OB and Pedersen, TH and Overgaard, J}, title = {Cold exposure causes cell death by depolarization-mediated Ca2+ overload in a chill-susceptible insect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9737-E9744}, pmid = {30254178}, issn = {1091-6490}, mesh = {Animals ; Calcium/*metabolism ; *Cell Death ; *Cold Temperature ; Hemolymph/*metabolism ; *Hyperkalemia ; Locusta migratoria/*physiology ; Membrane Potentials ; Muscles/cytology/*physiology ; Water-Electrolyte Balance ; }, abstract = {Cold tolerance of insects is arguably among the most important traits defining their geographical distribution. Even so, very little is known regarding the causes of cold injury in this species-rich group. In many insects it has been observed that cold injury coincides with a cellular depolarization caused by hypothermia and hyperkalemia that develop during chronic cold exposure. However, prior studies have been unable to determine if cold injury is caused by direct effects of hypothermia, by toxic effects of hyperkalemia, or by the depolarization that is associated with these perturbations. Here we use a fluorescent DNA-staining method to estimate cell viability of muscle and hindgut tissue from Locusta migratoria and show that the cellular injury is independent of the direct effects of hypothermia or toxic effects of hyperkalemia. Instead, we show that chill injury develops due to the associated cellular depolarization. We further hypothesized that the depolarization-induced injury was caused by opening of voltage-sensitive Ca2+ channels, causing a Ca2+ overload that triggers apoptotic/necrotic pathways. In accordance with this hypothesis, we show that hyperkalemic depolarization causes a marked increase in intracellular Ca2+ levels. Furthermore, using pharmacological manipulation of intra- and extracellular Ca2+ concentrations as well as Ca2+ channel conductance, we demonstrate that injury is prevented if transmembrane Ca2+ flux is prevented by removing extracellular Ca2+ or blocking Ca2+ influx. Together these findings demonstrate a causal relationship between cold-induced hyperkalemia, depolarization, and the development of chill injury through Ca2+-mediated necrosis/apoptosis.}, } @article {pmid30254177, year = {2018}, author = {Honda, T and Fujiyama, T and Miyoshi, C and Ikkyu, A and Hotta-Hirashima, N and Kanno, S and Mizuno, S and Sugiyama, F and Takahashi, S and Funato, H and Yanagisawa, M}, title = {A single phosphorylation site of SIK3 regulates daily sleep amounts and sleep need in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10458-10463}, pmid = {30254177}, issn = {1091-6490}, mesh = {Animals ; Homeostasis ; Male ; Mice ; Mice, Inbred C57BL ; *Mutation ; Neurons/cytology/*physiology ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Sleep/*physiology ; Wakefulness/*physiology ; }, abstract = {Sleep is an evolutionally conserved behavior from vertebrates to invertebrates. The molecular mechanisms that determine daily sleep amounts and the neuronal substrates for homeostatic sleep need remain unknown. Through a large-scale forward genetic screen of sleep behaviors in mice, we previously demonstrated that the Sleepy mutant allele of the Sik3 protein kinase gene markedly increases daily nonrapid-eye movement sleep (NREMS) amounts and sleep need. The Sleepy mutation deletes the in-frame exon 13 encoding a peptide stretch encompassing S551, a known PKA recognition site in SIK3. Here, we demonstrate that single amino acid changes at SIK3 S551 (S551A and S551D) reproduce the hypersomnia phenotype of the Sleepy mutant mice. These mice exhibit increased NREMS amounts and inherently increased sleep need, the latter demonstrated by increased duration of individual NREMS episodes and higher EEG slow-wave activity during NREMS. At the molecular level, deletion or mutation at SIK3 S551 reduces PKA recognition and abolishes 14-3-3 binding. Our results suggest that the evolutionally conserved S551 of SIK3 mediates, together with PKA and 14-3-3, the intracellular signaling crucial for the regulation of daily sleep amounts and sleep need at the organismal level.}, } @article {pmid30254176, year = {2018}, author = {Wen, J and Goyal, MS and Astafiev, SV and Raichle, ME and Yablonskiy, DA}, title = {Genetically defined cellular correlates of the baseline brain MRI signal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9727-E9736}, pmid = {30254176}, issn = {1091-6490}, support = {R01 AG054513/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Aged ; Brain/blood supply/*metabolism ; Brain Mapping ; Cerebrovascular Circulation ; Female ; *Gene Regulatory Networks ; *Genome, Human ; Humans ; Magnetic Resonance Imaging/*methods ; Male ; Middle Aged ; Young Adult ; }, abstract = {fMRI revolutionized neuroscience by allowing in vivo real-time detection of human brain activity. While the nature of the fMRI signal is understood as resulting from variations in the MRI signal due to brain-activity-induced changes in the blood oxygenation level (BOLD effect), these variations constitute a very minor part of a baseline MRI signal. Hence, the fundamental (and not addressed) questions are how underlying brain cellular composition defines this baseline MRI signal and how a baseline MRI signal relates to fMRI. Herein we investigate these questions by using a multimodality approach that includes quantitative gradient recalled echo (qGRE), volumetric and functional connectivity MRI, and gene expression data from the Allen Human Brain Atlas. We demonstrate that in vivo measurement of the major baseline component of a GRE signal decay rate parameter (R2t*) provides a unique genetic perspective into the cellular constituents of the human cortex and serves as a previously unidentified link between cortical tissue composition and fMRI signal. Data show that areas of the brain cortex characterized by higher R2t* have high neuronal density and have stronger functional connections to other brain areas. Interestingly, these areas have a relatively smaller concentration of synapses and glial cells, suggesting that myelinated cortical axons are likely key cortical structures that contribute to functional connectivity. Given these associations, R2t* is expected to be a useful signal in assessing microstructural changes in the human brain during development and aging in health and disease.}, } @article {pmid30254175, year = {2018}, author = {Steinbeck, J and Ross, IL and Rothnagel, R and Gäbelein, P and Schulze, S and Giles, N and Ali, R and Drysdale, R and Sierecki, E and Gambin, Y and Stahlberg, H and Takahashi, Y and Hippler, M and Hankamer, B}, title = {Structure of a PSI-LHCI-cyt b6f supercomplex in Chlamydomonas reinhardtii promoting cyclic electron flow under anaerobic conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10517-10522}, pmid = {30254175}, issn = {1091-6490}, mesh = {Anaerobiosis ; Chlamydomonas reinhardtii/growth & development/*metabolism ; Cytochrome b6f Complex/*chemistry/metabolism ; Electron Transport ; *Electrons ; Light-Harvesting Protein Complexes/*chemistry/metabolism ; Models, Molecular ; Multiprotein Complexes/*chemistry/metabolism ; Oxidation-Reduction ; *Photosynthesis ; Photosystem I Protein Complex/*chemistry/metabolism ; Protein Conformation ; }, abstract = {Photosynthetic linear electron flow (LEF) produces ATP and NADPH, while cyclic electron flow (CEF) exclusively drives photophosphorylation to supply extra ATP. The fine-tuning of linear and cyclic electron transport levels allows photosynthetic organisms to balance light energy absorption with cellular energy requirements under constantly changing light conditions. As LEF and CEF share many electron transfer components, a key question is how the same individual structural units contribute to these two different functional modes. Here, we report the structural identification of a photosystem I (PSI)-light harvesting complex I (LHCI)-cytochrome (cyt) b6f supercomplex isolated from the unicellular alga Chlamydomonas reinhardtii under anaerobic conditions, which induces CEF. This provides strong evidence for the model that enhanced CEF is induced by the formation of CEF supercomplexes, when stromal electron carriers are reduced, to generate additional ATP. The additional identification of PSI-LHCI-LHCII complexes is consistent with recent findings that both CEF enhancement and state transitions are triggered by similar conditions, but can occur independently from each other. Single molecule fluorescence correlation spectroscopy indicates a physical association between cyt b6f and fluorescent chlorophyll containing PSI-LHCI supercomplexes. Single particle analysis identified top-view projections of the corresponding PSI-LHCI-cyt b6f supercomplex. Based on molecular modeling and mass spectrometry analyses, we propose a model in which dissociation of LHCA2 and LHCA9 from PSI supports the formation of this CEF supercomplex. This is supported by the finding that a Δlhca2 knockout mutant has constitutively enhanced CEF.}, } @article {pmid30254174, year = {2018}, author = {Turner-Bridger, B and Jakobs, M and Muresan, L and Wong, HH and Franze, K and Harris, WA and Holt, CE}, title = {Single-molecule analysis of endogenous β-actin mRNA trafficking reveals a mechanism for compartmentalized mRNA localization in axons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9697-E9706}, pmid = {30254174}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 322817//European Research Council/International ; 102457/Z/13/A//Wellcome Trust/United Kingdom ; 085314/Z/08/Z//Wellcome Trust/United Kingdom ; }, mesh = {Actins/*metabolism ; Animals ; Biological Transport, Active/physiology ; Growth Cones/*metabolism ; *Models, Biological ; *Molecular Imaging ; Neurogenesis/*physiology ; RNA, Messenger/*metabolism ; Xenopus Proteins/*metabolism ; Xenopus laevis ; }, abstract = {During embryonic nervous system assembly, mRNA localization is precisely regulated in growing axons, affording subcellular autonomy by allowing controlled protein expression in space and time. Different sets of mRNAs exhibit different localization patterns across the axon. However, little is known about how mRNAs move in axons or how these patterns are generated. Here, we couple molecular beacon technology with highly inclined and laminated optical sheet microscopy to image single molecules of identified endogenous mRNA in growing axons. By combining quantitative single-molecule imaging with biophysical motion models, we show that β-actin mRNA travels mainly as single copies and exhibits different motion-type frequencies in different axonal subcompartments. We find that β-actin mRNA density is fourfold enriched in the growth cone central domain compared with the axon shaft and that a modicum of directed transport is vital for delivery of mRNA to the axon tip. Through mathematical modeling we further demonstrate that directional differences in motor-driven mRNA transport speeds are sufficient to generate β-actin mRNA enrichment at the growth cone. Our results provide insight into how mRNAs are trafficked in axons and a mechanism for generating different mRNA densities across axonal subcompartments.}, } @article {pmid30254173, year = {2018}, author = {Benoun, JM and Peres, NG and Wang, N and Pham, OH and Rudisill, VL and Fogassy, ZN and Whitney, PG and Fernandez-Ruiz, D and Gebhardt, T and Pham, QM and Puddington, L and Bedoui, S and Strugnell, RA and McSorley, SJ}, title = {Optimal protection against Salmonella infection requires noncirculating memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10416-10421}, pmid = {30254173}, issn = {1091-6490}, support = {P01 AI056172/AI/NIAID NIH HHS/United States ; R01 AI103422/AI/NIAID NIH HHS/United States ; R01 AI139410/AI/NIAID NIH HHS/United States ; T32 AI060555/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Female ; Immunization ; Immunologic Memory/*immunology ; Liver/*immunology/microbiology ; Mice ; Mice, Inbred C57BL ; Salmonella Infections/*immunology/microbiology/prevention & control ; Salmonella typhimurium/*immunology ; T-Lymphocytes/*immunology/microbiology ; Th1 Cells/*immunology/microbiology ; }, abstract = {While CD4 Th1 cells are required for resistance to intramacrophage infections, adoptive transfer of Th1 cells is insufficient to protect against Salmonella infection. Using an epitope-tagged vaccine strain of Salmonella, we found that effective protection correlated with expanded Salmonella-specific memory CD4 T cells in circulation and nonlymphoid tissues. However, naive mice that previously shared a blood supply with vaccinated partners lacked T cell memory with characteristics of tissue residence and did not acquire robust protective immunity. Using a YFP-IFN-γ reporter system, we identified Th1 cells in the liver of immunized mice that displayed markers of tissue residence, including P2X7, ARTC2, LFA-1, and CD101. Adoptive transfer of liver memory cells after ARTC2 blockade increased protection against highly virulent bacteria. Taken together, these data demonstrate that noncirculating memory Th1 cells are a vital component of immunity to Salmonella infection and should be the focus of vaccine strategies.}, } @article {pmid30254172, year = {2018}, author = {Ma, Y and Guo, H and Hu, L and Martinez, PP and Moschou, PN and Cevik, V and Ding, P and Duxbury, Z and Sarris, PF and Jones, JDG}, title = {Distinct modes of derepression of an Arabidopsis immune receptor complex by two different bacterial effectors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10218-10227}, pmid = {30254172}, issn = {1091-6490}, support = {BB/M008193/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L011646/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/*immunology/microbiology ; Arabidopsis Proteins/genetics/immunology/*metabolism ; Bacterial Proteins/*metabolism ; Fluorescence Resonance Energy Transfer ; Multiprotein Complexes/immunology ; Mutation ; Plant Diseases/immunology/microbiology ; Plant Immunity ; Plant Proteins/genetics/immunology/*metabolism ; Plants, Genetically Modified ; Protein Conformation ; Protein Domains ; Ralstonia solanacearum/pathogenicity ; Tobacco/genetics/immunology ; }, abstract = {Plant intracellular nucleotide-binding leucine-rich repeat (NLR) immune receptors often function in pairs to detect pathogen effectors and activate defense. The Arabidopsis RRS1-R-RPS4 NLR pair recognizes the bacterial effectors AvrRps4 and PopP2 via an integrated WRKY transcription factor domain in RRS1-R that mimics the effector's authentic targets. How the complex activates defense upon effector recognition is unknown. Deletion of the WRKY domain results in an RRS1 allele that triggers constitutive RPS4-dependent defense activation, suggesting that in the absence of effector, the WRKY domain contributes to maintaining the complex in an inactive state. We show the WRKY domain interacts with the adjacent domain 4, and that the inactive state of RRS1 is maintained by WRKY-domain 4 interactions before ligand detection. AvrRps4 interaction with the WRKY domain disrupts WRKY-domain 4 association, thus derepressing the complex. PopP2-triggered activation is less easily explained by such disruption and involves the longer C-terminal extension of RRS1-R. Furthermore, some mutations in RPS4 and RRS1 compromise PopP2 but not AvrRps4 recognition, suggesting that AvrRps4 and PopP2 derepress the complex differently. Consistent with this, a "reversibly closed" conformation of RRS1-R, engineered in a method exploiting the high affinity of colicin E9 and Im9 domains, reversibly loses AvrRps4, but not PopP2 responsiveness. Following RRS1 derepression, interactions between domain 4 and the RPS4 C-terminal domain likely contribute to activation. Simultaneous relief of autoinhibition and activation may contribute to defense activation in many immune receptors.}, } @article {pmid30254171, year = {2018}, author = {Scipion, CPM and Ghoshdastider, U and Ferrer, FJ and Yuen, TY and Wongsantichon, J and Robinson, RC}, title = {Structural evidence for the roles of divalent cations in actin polymerization and activation of ATP hydrolysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10345-10350}, pmid = {30254171}, issn = {1091-6490}, mesh = {Actins/*chemistry/*metabolism ; Adenosine Triphosphate/*metabolism ; Animals ; Cations, Divalent/*metabolism ; Crystallography, X-Ray ; Hydrolysis ; Magnesium/chemistry/metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Proteins/chemistry/metabolism ; Rabbits ; Water/chemistry ; }, abstract = {The structure of the actin filament is known at a resolution that has allowed the architecture of protein components to be unambiguously assigned. However, fully understanding the chemistry of the system requires higher resolution to identify the ions and water molecules involved in polymerization and ATP hydrolysis. Here, we find experimental evidence for the association of cations with the surfaces of G-actin in a 2.0-Å resolution X-ray structure of actin bound to a Cordon-Bleu WH2 motif and in previously determined high-resolution X-ray structures. Three of four reoccurring divalent cation sites were stable during molecular dynamics (MD) simulations of the filament, suggesting that these sites may play a functional role in stabilizing the filament. We modeled the water coordination at the ATP-bound Mg2+, which also proved to be stable during the MD simulations. Using this model of the filament with a hydrated ATP-bound Mg2+, we compared the cumulative probability of an activated hydrolytic water molecule approaching the γ-phosphorous of ATP, in comparison with G-actin, in the MD simulations. The cumulative probability increased in F-actin in line with the activation of actin's ATPase activity on polymerization. However, inclusion of the cations in the filament lowered cumulative probability, suggesting the rate of hydrolysis may be linked to filament flexibility. Together, these data extend the possible roles of Mg2+ in polymerization and the mechanism of polymerization-induced activation of actin's ATPase activity.}, } @article {pmid30254170, year = {2018}, author = {Osipov, VA and Kowalewski, M and Mukamel, S}, title = {Multiscale wavelet decomposition of time-resolved X-ray diffraction signals in cyclohexadiene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10269-10274}, pmid = {30254170}, issn = {1091-6490}, abstract = {We demonstrate how the wavelet transform, which is a powerful tool for compression, filtering, and scaling analysis of signals, may be used to separate large- and short-scale electron density features in X-ray diffraction patterns. Wavelets can isolate the electron density associated with delocalized bonds from the much stronger background of highly localized core electrons. The wavelet-processed signals clearly reveal the bond formation and breaking in the early steps of the photoinduced pericyclic ring opening reaction of 1,3-cyclohexadiene, which are not resolved in the bare signal.}, } @article {pmid30254169, year = {2018}, author = {Noack, A and Gericke, B and von Köckritz-Blickwede, M and Menze, A and Noack, S and Gerhauser, I and Osten, F and Naim, HY and Löscher, W}, title = {Mechanism of drug extrusion by brain endothelial cells via lysosomal drug trapping and disposal by neutrophils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9590-E9599}, pmid = {30254169}, issn = {1091-6490}, mesh = {ATP Binding Cassette Transporter, Subfamily B/metabolism ; Animals ; Blood-Brain Barrier/*metabolism/pathology ; Cell Line ; Endothelial Cells/*metabolism/pathology ; Humans ; Lysosomes/*metabolism/pathology ; Neutrophils/*metabolism/pathology ; Phagocytosis/*drug effects ; Swine ; Xenobiotics/*pharmacokinetics/pharmacology ; }, abstract = {The blood-brain barrier protects the brain against a variety of potentially toxic compounds. Barrier function results from tight junctions between brain capillary endothelial cells and high expression of active efflux transporters, including P-glycoprotein (Pgp), at the apical membrane of these cells. In addition to actively transporting drugs out of the cell, Pgp mediates lysosomal sequestration of chemotherapeutic drugs in cancer cells, thus contributing to drug resistance. Here, we describe that lysosomal sequestration of Pgp substrates, including doxorubicin, also occurs in human and porcine brain endothelial cells that form the blood-brain barrier. This is followed by shedding of drug-sequestering vesicular structures, which stay attached to the apical side of the plasma membrane and form aggregates ("barrier bodies") that ultimately undergo phagocytosis by neutrophils, thus constituting an as-yet-undescribed mechanism of drug disposal. These findings introduce a mechanism that might contribute to brain protection against potentially toxic xenobiotics, including therapeutically important chemotherapeutic drugs.}, } @article {pmid30254168, year = {2018}, author = {Lee, D and Takayama, S and Goldberg, AL}, title = {ZFAND5/ZNF216 is an activator of the 26S proteasome that stimulates overall protein degradation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9550-E9559}, pmid = {30254168}, issn = {1091-6490}, mesh = {Animals ; Cell-Free System/chemistry/metabolism ; DNA-Binding Proteins/*chemistry/genetics/metabolism ; Enzyme Activators/*chemistry/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Mice ; Mice, Transgenic ; Proteasome Endopeptidase Complex/*chemistry/genetics/metabolism ; Protein Domains ; *Proteolysis ; Recombinant Proteins/chemistry/genetics/metabolism ; Ubiquitination ; }, abstract = {ZFAND5/ZNF216, a member of the zinc finger AN1-type domain family, is abundant in heart and brain, but is induced in skeletal muscle during atrophy (although not in proteotoxic stress). Because mice lacking ZFAND5 exhibit decreased atrophy, a role in stimulating protein breakdown seemed likely. Addition of recombinant ZFAND5 to purified 26S proteasomes stimulated hydrolysis of ubiquitinated proteins, short peptides, and ATP. Mutating its C-terminal AN1 domain abolished the stimulation of proteasomal peptidase activity. Mutating its N-terminal zinc finger A20 domain, which binds ubiquitin chains, prevented the enhanced degradation of ubiquitinated proteins without affecting peptidase activity. Mouse embryonic fibroblast (MEF) cells lacking ZFAND5 had lower rates of protein degradation and proteasomal activity than WT MEFs. ZFAND5 addition to cell lysates stimulated proteasomal activity and protein degradation. Unlike other proteasome regulators, ZFAND5 enhances multiple 26S activities and overall cellular protein breakdown.}, } @article {pmid30254167, year = {2018}, author = {Sun, T and Hobbie, SE and Berg, B and Zhang, H and Wang, Q and Wang, Z and Hättenschwiler, S}, title = {Contrasting dynamics and trait controls in first-order root compared with leaf litter decomposition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10392-10397}, pmid = {30254167}, issn = {1091-6490}, mesh = {Carbon/metabolism ; Ecosystem ; Mycorrhizae/classification/*physiology ; Nitrogen/metabolism ; Phenotype ; Plant Leaves/*chemistry/metabolism ; Plant Roots/*chemistry/metabolism ; Soil/*chemistry ; Species Specificity ; }, abstract = {Decomposition is a key component of the global carbon (C) cycle, yet current ecosystem C models do not adequately represent the contributions of plant roots and their mycorrhizae to this process. The understanding of decomposition dynamics and their control by traits is particularly limited for the most distal first-order roots. Here we followed decomposition of first-order roots and leaf litter from 35 woody plant species differing in mycorrhizal type over 6 years in a Chinese temperate forest. First-order roots decomposed more slowly (k = 0.11 ± 0.01 years-1) than did leaf litter (0.35 ± 0.02 years-1), losing only 35% of initial mass on average after 6 years of exposure in the field. In contrast to leaf litter, nonlignin root C chemistry (nonstructural carbohydrates, polyphenols) accounted for 82% of the large interspecific variation in first-order root decomposition. Leaf litter from ectomycorrhizal (EM) species decomposed more slowly than that from arbuscular mycorrhizal (AM) species, whereas first-order roots of EM species switched, after 2 years, from having slower to faster decomposition compared with those from AM species. The fundamentally different dynamics and control mechanisms of first-order root decomposition compared with those of leaf litter challenge current ecosystem C models, the recently suggested dichotomy between EM and AM plants, and the idea that common traits can predict decomposition across roots and leaves. Aspects of C chemistry unrelated to lignin or nitrogen, and not presently considered in decomposition models, controlled first-order root decomposition; thus, current paradigms of ecosystem C dynamics and model parameterization require revision.}, } @article {pmid30254166, year = {2018}, author = {Fong, JJ and Tsai, CM and Saha, S and Nizet, V and Varki, A and Bui, JD}, title = {Siglec-7 engagement by GBS β-protein suppresses pyroptotic cell death of natural killer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10410-10415}, pmid = {30254166}, issn = {1091-6490}, support = {P01 HL107150/HL/NHLBI NIH HHS/United States ; R01 CA157885/CA/NCI NIH HHS/United States ; R01 GM032373/GM/NIGMS NIH HHS/United States ; }, mesh = {Antigens, Differentiation, Myelomonocytic/genetics/*metabolism ; Cells, Cultured ; DNA-Binding Proteins/genetics/*metabolism ; Humans ; Immunity, Innate/*immunology ; Inflammation Mediators/*metabolism ; Killer Cells, Natural/immunology/metabolism/*pathology ; Lectins/genetics/*metabolism ; *Pyroptosis ; }, abstract = {Natural killer (NK) cells are innate immune lymphocytes that recognize and destroy abnormal host cells, such as tumor cells or those infected by viral pathogens. To safely accomplish these functions, NK cells display activating receptors that detect stress molecules or viral ligands displayed at the cell surface, balanced by inhibitory receptors that bind to self-molecules. To date, such activating and inhibitory receptors on NK cells are not known to recognize bacterial determinants. Moreover, NK cell responses to direct interactions with extracellular bacteria are poorly explored. In this study, we observed the human neonatal pathogen group B Streptococcus (GBS) can directly engage human NK cells. The interaction was mediated through the B6N segment of streptococcal β-protein, binding to the inhibitory receptor Siglec-7 via its amino-terminal V-set domain. Unlike classical Siglec binding, the interaction is also independent of its sialic acid recognition property. In contrast to WT GBS, mutants lacking β-protein induced efficient pyroptosis of NK cells through the NLRP3 inflammasome, with production and secretion of the proinflammatory cytokine IL-1β and dissemination of the cytotoxic molecule granzyme B. We postulate that GBS evolved β-protein engagement of inhibitory human Siglec-7 to suppress the pyroptotic response of NK cells and thereby block recruitment of a broader innate immune response, i.e., by "silencing the sentinel."}, } @article {pmid30254165, year = {2018}, author = {Baker, SK and Chen, ZL and Norris, EH and Revenko, AS and MacLeod, AR and Strickland, S}, title = {Blood-derived plasminogen drives brain inflammation and plaque deposition in a mouse model of Alzheimer's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9687-E9696}, pmid = {30254165}, issn = {1091-6490}, support = {R01 NS106668/NS/NINDS NIH HHS/United States ; T32 GM066699/GM/NIGMS NIH HHS/United States ; }, mesh = {Alzheimer Disease/*blood/drug therapy/genetics/pathology ; Amyloid beta-Peptides/genetics/metabolism ; Animals ; Brain/*metabolism/pathology ; Disease Models, Animal ; Inflammation/drug therapy/genetics/metabolism/pathology ; Mice ; Mice, Transgenic ; Oligodeoxyribonucleotides, Antisense/pharmacology ; Plasminogen/antagonists & inhibitors/genetics/*metabolism ; }, abstract = {Two of the most predominant features of the Alzheimer's disease (AD) brain are deposition of β-amyloid (Aβ) plaques and inflammation. The mechanism behind these pathologies remains unknown, but there is evidence to suggest that inflammation may predate the deposition of Aβ. Furthermore, immune activation is increasingly being recognized as a major contributor to the pathogenesis of the disease, and disorders involving systemic inflammation, such as infection, aging, obesity, atherosclerosis, diabetes, and depression are risk factors for the development of AD. Plasminogen (PLG) is primarily a blood protein synthesized in the liver, which when cleaved into its active form, plasmin (PL), plays roles in fibrinolysis, wound healing, cell signaling, and inflammatory regulation. Here we show that PL in the blood is a regulator of brain inflammatory action and AD pathology. Depletion of PLG in the plasma of an AD mouse model through antisense oligonucleotide technology dramatically improved AD pathology and decreased glial cell activation in the brain, whereas an increase in PL activity through α-2-antiplasmin (A2AP) antisense oligonucleotide treatment exacerbated the brain's immune response and plaque deposition. These studies suggest a crucial role for peripheral PL in mediating neuroimmune cell activation and AD progression and could provide a link to systemic inflammatory risk factors that are known to be associated with AD development.}, } @article {pmid30254164, year = {2018}, author = {Hong, SH and Fang, S and Lu, BC and Nofsinger, R and Kawakami, Y and Castro, GL and Yin, Y and Lin, C and Yu, RT and Downes, M and Izpisúa Belmonte, JC and Shilatifard, A and Evans, RM}, title = {Corepressor SMRT is required to maintain Hox transcriptional memory during somitogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10381-10386}, pmid = {30254164}, issn = {1091-6490}, support = {R01 HL105278/HL/NHLBI NIH HHS/United States ; R37 DK057978/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology ; *Gene Expression Regulation ; Genes, Homeobox/*genetics ; Mice ; Mice, Inbred C57BL ; Neural Crest/cytology/physiology ; Nuclear Receptor Co-Repressor 2/*physiology ; Somites/cytology/drug effects/*physiology ; *Transcription, Genetic ; Tretinoin/*pharmacology ; }, abstract = {Nuclear hormone receptors (NRs), such as retinoic acid receptors (RARs), play critical roles in vertebrate development and homeostasis by regulating target gene transcription. Their activity is controlled by ligand-dependent release of corepressors and subsequent recruitment of coactivators, but how these individual receptor modes contribute to development are unknown. Here, we show that mice carrying targeted knockin mutations in the corepressor Silencing Mediator of Retinoid and Thyroid hormone receptor (SMRT) that specifically disable SMRT function in NR signaling (SMRTmRID), display defects in cranial neural crest cell-derived structures and posterior homeotic transformations of axial vertebrae. SMRTmRID embryos show enhanced transcription of RAR targets including Hox loci, resulting in respecification of vertebral identities. Up-regulated histone acetylation and decreased H3K27 methylation are evident in the Hox loci whose somitic expression boundaries are rostrally shifted. Furthermore, enhanced recruitment of super elongation complex is evident in rapidly induced non-Pol II-paused targets in SMRTmRID embryonic stem cells. These results demonstrate that SMRT-dependent repression of RAR is critical to establish and maintain the somitic Hox code and segmental identity during fetal development via epigenetic marking of target loci.}, } @article {pmid30254163, year = {2018}, author = {Bím, D and Maldonado-Domínguez, M and Rulíšek, L and Srnec, M}, title = {Beyond the classical thermodynamic contributions to hydrogen atom abstraction reactivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {E10287-E10294}, pmid = {30254163}, issn = {1091-6490}, abstract = {Hydrogen atom abstraction (HAA) reactions are cornerstones of chemistry. Various (metallo)enzymes performing the HAA catalysis evolved in nature and inspired the rational development of multiple synthetic catalysts. Still, the factors determining their catalytic efficiency are not fully understood. Herein, we define the simple thermodynamic factor η by employing two thermodynamic cycles: one for an oxidant (catalyst), along with its reduced, protonated, and hydrogenated form; and one for the substrate, along with its oxidized, deprotonated, and dehydrogenated form. It is demonstrated that η reflects the propensity of the substrate and catalyst for (a)synchronicity in concerted H+/e- transfers. As such, it significantly contributes to the activation energies of the HAA reactions, in addition to a classical thermodynamic (Bell-Evans-Polanyi) effect. In an attempt to understand the physicochemical interpretation of η, we discovered an elegant link between η and reorganization energy λ from Marcus theory. We discovered computationally that for a homologous set of HAA reactions, λ reaches its maximum for the lowest |η|, which then corresponds to the most synchronous HAA mechanism. This immediately implies that among HAA processes with the same reaction free energy, ΔG0, the highest barrier (≡ΔG≠) is expected for the most synchronous proton-coupled electron (i.e., hydrogen) transfer. As proof of concept, redox and acidobasic properties of nonheme FeIVO complexes are correlated with activation free energies for HAA from C-H and O-H bonds. We believe that the reported findings may represent a powerful concept in designing new HAA catalysts.}, } @article {pmid30254162, year = {2018}, author = {Lee, M and Bai, C and Feliks, M and Alhadeff, R and Warshel, A}, title = {On the control of the proton current in the voltage-gated proton channel Hv1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10321-10326}, pmid = {30254162}, issn = {1091-6490}, support = {R35 GM122472/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Membrane/metabolism ; Ion Channels/*chemistry/genetics/*metabolism ; Models, Molecular ; Molecular Dynamics Simulation ; Protons ; Recombinant Proteins/chemistry/genetics/metabolism ; }, abstract = {The nature of the action of voltage-activated proton transport proteins is a conundrum of great current interest. Here we approach this issue by exploring the action of Hv1, a voltage-gated proton channel found in different cells in humans and other organisms. Our study focuses on evaluating the free energy of transporting a proton through the channel, as well as the effect of the proton transfer through D112, in both the closed and open channel conformations. It is found that D112 allows a transported proton to bypass the electrostatic barrier of the open channel, while not being able to help in passing the barrier in the closed form. This reflects the change in position of the gating arginine residues relative to D112, upon voltage activation. Significantly, the effect of D112 accounts for the observed trend in selectivity by overcoming the electrostatic barrier at its highest point. Thus, the calculations provide a structure/function correlation for the Hv1 system. The present work also clarifies that the action of Hv1 is not controlled by a Grotthuss mechanism but, as is always the case, by the protein electrostatic potential at the rate-limiting barriers.}, } @article {pmid30254161, year = {2018}, author = {Kotani, T and Kirisako, H and Koizumi, M and Ohsumi, Y and Nakatogawa, H}, title = {The Atg2-Atg18 complex tethers pre-autophagosomal membranes to the endoplasmic reticulum for autophagosome formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10363-10368}, pmid = {30254161}, issn = {1091-6490}, mesh = {Autophagosomes/chemistry/*metabolism ; Autophagy-Related Proteins/genetics/*metabolism ; Endoplasmic Reticulum/*metabolism ; Intracellular Membranes/metabolism ; Membrane Proteins/genetics/*metabolism ; Multiprotein Complexes/chemistry/metabolism ; Phosphatidylinositol Phosphates/metabolism ; Protein Domains ; Saccharomyces cerevisiae/cytology/metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; }, abstract = {The biogenesis of double-membrane vesicles called autophagosomes, which sequester and transport intracellular material for degradation in lysosomes or vacuoles, is a central event in autophagy. This process requires a unique set of factors called autophagy-related (Atg) proteins. The Atg proteins assemble to organize the preautophagosomal structure (PAS), at which a cup-shaped membrane, the isolation membrane (or phagophore), forms and expands to become the autophagosome. The molecular mechanism of autophagosome biogenesis remains poorly understood. Previous studies have shown that Atg2 forms a complex with the phosphatidylinositol 3-phosphate (PI3P)-binding protein Atg18 and localizes to the PAS to initiate autophagosome biogenesis; however, the molecular function of Atg2 remains unknown. In this study, we show that Atg2 has two membrane-binding domains in the N- and C-terminal regions and acts as a membrane tether during autophagosome formation in the budding yeast Saccharomyces cerevisiae An amphipathic helix in the C-terminal region binds to membranes and facilitates Atg18 binding to PI3P to target the Atg2-Atg18 complex to the PAS. The N-terminal region of Atg2 is also involved in the membrane binding of this protein but is dispensable for the PAS targeting of the Atg2-Atg18 complex. Our data suggest that this region associates with the endoplasmic reticulum (ER) and is responsible for the formation of the isolation membrane at the PAS. Based on these results, we propose that the Atg2-Atg18 complex tethers the PAS to the ER to initiate membrane expansion during autophagosome formation.}, } @article {pmid30254160, year = {2018}, author = {O'Keeffe, NJ and Zheng, Z and Huppert, HE and Linden, PF}, title = {Symmetric coalescence of two hydraulic fractures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10228-10232}, pmid = {30254160}, issn = {1091-6490}, abstract = {The formation of a fracture network is a key process for many geophysical and industrial practices from energy resource recovery to induced seismic management. We focus on the initial stage of a fracture network formation using experiments on the symmetric coalescence of two equal coplanar, fluid-driven, penny-shaped fractures in a brittle elastic medium. Initially, the fractures propagate independently of each other. The fractures then begin to interact and coalesce, forming a bridge between them. Within an intermediate period after the initial contact, most of the fracture growth is localized along this bridge, perpendicular to the line connecting the injection sources. Using light attenuation and particle image velocimetry to measure both the fracture aperture and velocity field, we characterize the growth of this bridge. We model this behavior using a geometric volume conservation argument dependent on the symmetry of the interaction, with a 2D approximation for the bridge. We also verify experimentally the scaling for the bridge growth and the shape of the thickness profile along the bridge. The influence of elasticity and toughness of the solid, injection rate of the fluid, and initial location of the fractures are captured by our scaling.}, } @article {pmid30254159, year = {2018}, author = {Li, AG and Murphy, EC and Culhane, AC and Powell, E and Wang, H and Bronson, RT and Von, T and Giobbie-Hurder, A and Gelman, RS and Briggs, KJ and Piwnica-Worms, H and Zhao, JJ and Kung, AL and Kaelin, WG and Livingston, DM}, title = {BRCA1-IRIS promotes human tumor progression through PTEN blockade and HIF-1α activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9600-E9609}, pmid = {30254159}, issn = {1091-6490}, support = {P01 CA080111/CA/NCI NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; }, mesh = {*Alternative Splicing ; Animals ; BRCA1 Protein/genetics/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Mice ; Neoplasms/genetics/*metabolism/pathology ; PTEN Phosphohydrolase/genetics/*metabolism ; *Signal Transduction ; }, abstract = {BRCA1 is an established breast and ovarian tumor suppressor gene that encodes multiple protein products whose individual contributions to human cancer suppression are poorly understood. BRCA1-IRIS (also known as "IRIS"), an alternatively spliced BRCA1 product and a chromatin-bound replication and transcription regulator, is overexpressed in various primary human cancers, including breast cancer, lung cancer, acute myeloid leukemia, and certain other carcinomas. Its naturally occurring overexpression can promote the metastasis of patient-derived xenograft (PDX) cells and other human cancer cells in mouse models. The IRIS-driven metastatic mechanism results from IRIS-dependent suppression of phosphatase and tensin homolog (PTEN) transcription, which in turn perturbs the PI3K/AKT/GSK-3β pathway leading to prolyl hydroxylase-independent HIF-1α stabilization and activation in a normoxic environment. Thus, despite the tumor-suppressing genetic origin of IRIS, its properties more closely resemble those of an oncoprotein that, when spontaneously overexpressed, can, paradoxically, drive human tumor progression.}, } @article {pmid30254158, year = {2018}, author = {Chinthalapudi, K and Rangarajan, ES and Izard, T}, title = {The interaction of talin with the cell membrane is essential for integrin activation and focal adhesion formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10339-10344}, pmid = {30254158}, issn = {1091-6490}, mesh = {Allosteric Regulation ; Animals ; Binding Sites ; CHO Cells ; Cell Membrane/*metabolism ; Cricetulus ; Crystallography, X-Ray ; Focal Adhesions/*physiology ; Integrins/*metabolism ; Models, Molecular ; Phosphatidylinositol 4,5-Diphosphate/chemistry/metabolism ; Protein Conformation ; Protein Domains ; Talin/*chemistry/genetics/*metabolism ; }, abstract = {Multicellular organisms have well-defined, tightly regulated mechanisms for cell adhesion. Heterodimeric αβ integrin receptors play central roles in this function and regulate processes for normal cell functions, including signaling, cell migration, and development, binding to the extracellular matrix, and senescence. They are involved in hemostasis and the immune response, participate in leukocyte function, and have biological implications in angiogenesis and cancer. Proper control of integrin activation for cellular communication with the external environment requires several physiological processes. Perturbation of these equilibria may lead to constitutive integrin activation that results in bleeding disorders. Furthermore, integrins play key roles in cancer progression and metastasis in which certain tumor types exhibit higher levels of various integrins. Thus, the integrin-associated signaling complex is important for cancer therapy development. During inside-out signaling, the cytoskeletal protein talin plays a key role in regulating integrin affinity whereby the talin head domain activates integrin by binding to the cytoplasmic tail of β-integrin and acidic membrane phospholipids. To understand the mechanism of integrin activation by talin, we determined the crystal structure of the talin head domain bound to the acidic phospholipid phosphatidylinositol 4,5-bisphosphate (PIP2), allowing us to design a lipid-binding-deficient talin mutant. Our confocal microscopy with talin knockout cells suggests that the talin-cell membrane interaction seems essential for focal adhesion formation and stabilization. Basal integrin activation in Chinese hamster ovary cells suggests that the lipid-binding-deficient talin mutant inhibits integrin activation. Thus, membrane attachment of talin seems necessary for integrin activation and focal adhesion formation.}, } @article {pmid30254157, year = {2018}, author = {Seaton, DD and Toledo-Ortiz, G and Ganpudi, A and Kubota, A and Imaizumi, T and Halliday, KJ}, title = {Dawn and photoperiod sensing by phytochrome A.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10523-10528}, pmid = {30254157}, issn = {1091-6490}, support = {R01 GM079712/GM/NIGMS NIH HHS/United States ; BB/M025551/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N005147/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Anthocyanins/metabolism ; Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; *Circadian Rhythm ; Gene Expression Regulation, Plant ; Light ; *Photoperiod ; Phytochrome A/genetics/*metabolism ; Plants, Genetically Modified/genetics/growth & development/*metabolism ; }, abstract = {In plants, light receptors play a pivotal role in photoperiod sensing, enabling them to track seasonal progression. Photoperiod sensing arises from an interaction between the plant's endogenous circadian oscillator and external light cues. Here, we characterize the role of phytochrome A (phyA) in photoperiod sensing. Our metaanalysis of functional genomic datasets identified phyA as a principal regulator of morning-activated genes, specifically in short photoperiods. We demonstrate that PHYA expression is under the direct control of the PHYTOCHROME INTERACTING FACTOR transcription factors, PIF4 and PIF5. As a result, phyA protein accumulates during the night, especially in short photoperiods. At dawn, phyA activation by light results in a burst of gene expression, with consequences for physiological processes such as anthocyanin accumulation. The combination of complex regulation of PHYA transcript and the unique molecular properties of phyA protein make this pathway a sensitive detector of both dawn and photoperiod.}, } @article {pmid30254156, year = {2018}, author = {Labouesse, MA and Sartori, AM and Weinmann, O and Simpson, EH and Kellendonk, C and Weber-Stadlbauer, U}, title = {Striatal dopamine 2 receptor upregulation during development predisposes to diet-induced obesity by reducing energy output in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10493-10498}, pmid = {30254156}, issn = {1091-6490}, support = {R01 MH093672/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Corpus Striatum/*metabolism ; Diet/*adverse effects ; *Energy Metabolism ; Humans ; Male ; Mice ; Mice, Transgenic ; Neostriatum/*metabolism ; Obesity/*etiology/pathology ; Receptors, Dopamine D2/*physiology ; Weight Gain ; }, abstract = {Dopaminergic signaling in the striatum, particularly at dopamine 2 receptors (D2R), has been a topic of active investigation in obesity research in the past decades. However, it still remains unclear whether variations in striatal D2Rs modulate the risk for obesity and if so in which direction. Human studies have yielded contradictory findings that likely reflect a complex nonlinear relationship, possibly involving a combination of causal effects and compensatory changes. Animal work indicates that although chronic obesogenic diets reduce striatal D2R function, striatal D2R down-regulation does not lead to obesity. In this study, we evaluated the consequences of striatal D2R up-regulation on body-weight gain susceptibility and energy balance in mice. We used a mouse model of D2R overexpression (D2R-OE) in which D2Rs were selectively up-regulated in striatal medium spiny neurons. We uncover a pathological mechanism by which striatal D2R-OE leads to reduced brown adipose tissue thermogenesis, reduced energy expenditure, and accelerated obesity despite reduced eating. We also show that D2R-OE restricted to development is sufficient to promote obesity and to induce energy-balance deficits. Together, our findings indicate that striatal D2R-OE during development persistently increases the propensity for obesity by reducing energy output in mice. This suggests that early alterations in the striatal dopamine system could represent a key predisposition factor toward obesity.}, } @article {pmid30254155, year = {2018}, author = {Chien, MH and Brameshuber, M and Rossboth, BK and Schütz, GJ and Schmid, S}, title = {Single-molecule optical absorption imaging by nanomechanical photothermal sensing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11150-11155}, pmid = {30254155}, issn = {1091-6490}, mesh = {Gold/chemistry ; Lasers ; Light ; Microscopy/*methods ; Nanoparticles/*chemistry ; Nanostructures/chemistry ; Nanotechnology/*methods ; Optics and Photonics/*methods ; Scattering, Radiation ; Signal-To-Noise Ratio ; Silicon Compounds/chemistry ; Temperature ; }, abstract = {Absorption microscopy is a promising alternative to fluorescence microscopy for single-molecule imaging. So far, molecular absorption has been probed optically via the attenuation of a probing laser or via photothermal effects. The sensitivity of optical probing is not only restricted by background scattering but it is fundamentally limited by laser shot noise, which minimizes the achievable single-molecule signal-to-noise ratio. Here, we present nanomechanical photothermal microscopy, which overcomes the scattering and shot-noise limit by detecting the photothermal heating of the sample directly with a temperature-sensitive substrate. We use nanomechanical silicon nitride drums, whose resonant frequency detunes with local heating. Individual Au nanoparticles with diameters from 10 to 200 nm and single molecules (Atto 633) are scanned with a heating laser with a peak irradiance of 354 ± 45 µW/µm2 using 50× long-working-distance objective. With a stress-optimized drum we reach a sensitivity of 16 fW/Hz1/2 at room temperature, resulting in a single-molecule signal-to-noise ratio of >70. The high sensitivity combined with the inherent wavelength independence of the nanomechanical sensor presents a competitive alternative to established tools for the analysis and localization of nonfluorescent single molecules and nanoparticles.}, } @article {pmid30254154, year = {2018}, author = {Yan, Y and Zhaoping, L and Li, W}, title = {Bottom-up saliency and top-down learning in the primary visual cortex of monkeys.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10499-10504}, pmid = {30254154}, issn = {1091-6490}, mesh = {Animals ; Attention/*physiology ; Learning/*physiology ; Macaca mulatta ; Male ; Models, Neurological ; Orientation/*physiology ; Photic Stimulation ; Visual Cortex/*physiology ; Visual Perception/*physiology ; }, abstract = {Early sensory cortex is better known for representing sensory inputs but less for the effect of its responses on behavior. Here we explore the behavioral correlates of neuronal responses in primary visual cortex (V1) in a task to detect a uniquely oriented bar-the orientation singleton-in a background of uniformly oriented bars. This singleton is salient or inconspicuous when the orientation contrast between the singleton and background bars is sufficiently large or small, respectively. Using implanted microelectrodes, we measured V1 activities while monkeys were trained to quickly saccade to the singleton. A neuron's responses to the singleton within its receptive field had an early and a late component, both increased with the orientation contrast. The early component started from the outset of neuronal responses; it remained unchanged before and after training on the singleton detection. The late component started ∼40 ms after the early one; it emerged and evolved with practicing the detection task. Training increased the behavioral accuracy and speed of singleton detection and increased the amount of information in the late response component about a singleton's presence or absence. Furthermore, for a given singleton, faster detection performance was associated with higher V1 responses; training increased this behavioral-neural correlate in the early V1 responses but decreased it in the late V1 responses. Therefore, V1's early responses are directly linked with behavior and represent the bottom-up saliency signals. Learning strengthens this link, likely serving as the basis for making the detection task more reflexive and less top-down driven.}, } @article {pmid30254153, year = {2018}, author = {Koll, DDB and Cronin, TW}, title = {Earth's outgoing longwave radiation linear due to H2O greenhouse effect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10293-10298}, pmid = {30254153}, issn = {1091-6490}, abstract = {Satellite measurements and radiative calculations show that Earth's outgoing longwave radiation (OLR) is an essentially linear function of surface temperature over a wide range of temperatures (≳60 K). Linearity implies that radiative forcing has the same impact in warmer as in colder climates and is thus of fundamental importance for understanding past and future climate change. Although the evidence for a nearly linear relation was first pointed out more than 50 y ago, it is still unclear why this relation is valid and when it breaks down. Here we present a simple semianalytical model that explains Earth's linear OLR as an emergent property of an atmosphere whose greenhouse effect is dominated by a condensable gas. Linearity arises from a competition between the surface's increasing thermal emission and the narrowing of spectral window regions with warming and breaks down at high temperatures once continuum absorption cuts off spectral windows. Our model provides a way of understanding the longwave contribution to Earth's climate sensitivity and suggests that extrasolar planets with other condensable greenhouse gases could have climate dynamics similar to Earth's.}, } @article {pmid30254152, year = {2018}, author = {Roch, S and Rohe, K}, title = {Generalized least squares can overcome the critical threshold in respondent-driven sampling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10299-10304}, pmid = {30254152}, issn = {1091-6490}, abstract = {To sample marginalized and/or hard-to-reach populations, respondent-driven sampling (RDS) and similar techniques reach their participants via peer referral. Under a Markov model for RDS, previous research has shown that if the typical participant refers too many contacts, then the variance of common estimators does not decay like [Formula: see text], where n is the sample size. This implies that confidence intervals will be far wider than under a typical sampling design. Here we show that generalized least squares (GLS) can effectively reduce the variance of RDS estimates. In particular, a theoretical analysis indicates that the variance of the GLS estimator is [Formula: see text] We then derive two classes of feasible GLS estimators. The first class is based upon a Degree Corrected Stochastic Blockmodel for the underlying social network. The second class is based upon a rank-two model. It might be of independent interest that in both model classes, the theoretical results show that it is possible to estimate the spectral properties of the population network from a random walk sample of the nodes. These theoretical results point the way to entirely different classes of estimators that account for the network structure beyond node degree. Diagnostic plots help to identify situations where feasible GLS estimators are more appropriate. The computational experiments show the potential benefits and also indicate that there is room to further develop these estimators in practical settings.}, } @article {pmid30254151, year = {2018}, author = {Besley, T and Dixit, A}, title = {Environmental catastrophes and mitigation policies in a multiregion world.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802864115}, pmid = {30254151}, issn = {1091-6490}, abstract = {In this paper we present a simple model for assessing the willingness to pay for reductions in the risk associated with catastrophic climate change. The model is extremely tractable and applies to a multiregion world but with global externalities and has five key features: (i) Neither the occurrence nor the costs of a catastrophic event in any one year are precisely predictable; (ii) the probability of a catastrophe occurring in any one year increases as the levels of greenhouse gases in the atmosphere increase; (iii) greenhouse gases are a worldwide public bad with emissions from any one country or region increasing the risks for all; (iv) there is two-sided irreversibility; if nothing is done and the problem proves serious, the climate, economic activity, and human life will suffer permanent damage, but if we spend large sums on countermeasures and the problem turns out to be minor or even nonexistent, we will have wasted resources unnecessarily; and (v) technological progress may yield partial or even complete solutions. The framework that we propose can give a sense of the quantitative significance of mitigation strategies. We illustrate these for a core set of parameter values.}, } @article {pmid30254086, year = {2018}, author = {DeCicco, JM and Schlesinger, WH}, title = {Opinion: Reconsidering bioenergy given the urgency of climate protection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9642-9645}, pmid = {30254086}, issn = {1091-6490}, mesh = {*Biofuels ; Carbon Cycle ; Carbon Dioxide/metabolism ; *Climate Change ; Ecology ; Global Warming ; Research ; }, } @article {pmid30253785, year = {2018}, author = {Telles, S and Kala, N and Sharma, SK and Balkrishna, A}, title = {Anthropometric variables as predictors of aspects of quality of life in persons with central obesity.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {680}, pmid = {30253785}, issn = {1756-0500}, mesh = {Adult ; Anthropometry ; Body Mass Index ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2 ; Female ; Humans ; India ; Male ; Middle Aged ; Obesity ; Obesity, Abdominal/*complications ; *Quality of Life ; Risk Factors ; Waist Circumference ; Waist-Hip Ratio ; }, abstract = {OBJECTIVE: Central obesity has been shown to negatively influence the quality of life in centrally obese persons of both sexes. In a population of 740 centrally obese Asian-Indian adults, the present study was conducted to determine whether body mass index (BMI), waist circumference, hip circumference (HC), waist-hip ratio (WHR) and sagittal abdominal diameter (SAD) could predict different domains of quality of life. The differences based on gender and age were also determined. Linear regression analyses were carried out and the level of statistical significance (α) was set at 0.05.

RESULTS: Body mass index, HC, WHR and SAD were significant predictors for different domains of quality of life as well as for the summated total quality of life. BMI was found to be the most important predictor among all predictors across age groups and both sexes.}, } @article {pmid30253781, year = {2018}, author = {Olney, KC and Nyer, DB and Vargas, DA and Wilson Sayres, MA and Haynes, KA}, title = {The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {83}, pmid = {30253781}, issn = {1752-0509}, support = {K01 CA188164/CA/NCI NIH HHS/United States ; K01 CA188164//National Cancer Institute/ ; 14-082976//Arizona Biomedical Research Commission/ ; }, abstract = {BACKGROUND: Mounting evidence from genome-wide studies of cancer shows that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable evasion of the immune system. Drugging the cancer epigenome with small molecule inhibitors to release silenced genes from the repressed state has emerged as a powerful approach for cancer research and drug development. Targets of these inhibitors include chromatin-modifying enzymes that can acquire drug-resistant mutations. In order to directly target a generally conserved feature, elevated trimethyl-lysine 27 on histone H3 (H3K27me3), we developed the Polycomb-based Transcription Factor (PcTF), a fusion activator that targets methyl-histone marks via its N-terminal H3K27me3-binding motif, and co-regulates sets of silenced genes.

RESULTS: Here, we report transcriptome profiling analyses of PcTF-treated breast cancer model cell lines. We identified a set of 19 PcTF-upregulated genes, or PUGs, that were consistent across three distinct breast cancer cell lines. These genes are associated with the interferon response pathway.

CONCLUSIONS: Our results demonstrate for the first time a chromatin-mediated interferon-related transcriptional response driven by an engineered fusion protein that physically links repressive histone marks with active transcription.}, } @article {pmid30253762, year = {2018}, author = {Sonntag, M and Blosa, M and Schmidt, S and Reimann, K and Blum, K and Eckrich, T and Seeger, G and Hecker, D and Schick, B and Arendt, T and Engel, J and Morawski, M}, title = {Synaptic coupling of inner ear sensory cells is controlled by brevican-based extracellular matrix baskets resembling perineuronal nets.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {99}, pmid = {30253762}, issn = {1741-7007}, abstract = {BACKGROUND: Perineuronal nets (PNNs) are specialized aggregations of extracellular matrix (ECM) molecules surrounding specific neurons in the central nervous system (CNS). PNNs are supposed to control synaptic transmission and are frequently associated with neurons firing at high rates, including principal neurons of auditory brainstem nuclei. The origin of high-frequency activity of auditory brainstem neurons is the indefatigable sound-driven transmitter release of inner hair cells (IHCs) in the cochlea.

RESULTS: Here, we show that synaptic poles of IHCs are ensheathed by basket-like ECM complexes formed by the same molecules that constitute PNNs of neurons in the CNS, including brevican, aggreccan, neurocan, hyaluronan, and proteoglycan link proteins 1 and 4 and tenascin-R. Genetic deletion of brevican, one of the main components, resulted in a massive degradation of ECM baskets at IHCs, a significant impairment in spatial coupling of pre- and postsynaptic elements and mild impairment of hearing.

CONCLUSIONS: These ECM baskets potentially contribute to control of synaptic transmission at IHCs and might be functionally related to PNNs of neurons in the CNS.}, } @article {pmid30253757, year = {2018}, author = {Coate, TM and Conant, K}, title = {Brevican "nets" voltage-gated calcium channels at the hair cell ribbon synapse.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {105}, pmid = {30253757}, issn = {1741-7007}, support = {R00 DC013107/DC/NIDCD NIH HHS/United States ; R01 DC016595/DC/NIDCD NIH HHS/United States ; R01 NS108810/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Brevican ; *Calcium ; Extracellular Matrix ; Hair ; Synapses ; }, abstract = {During hearing in mammals, "sensorineural" inner hair cells convert sound wave-generated mechanical input into electrical activity, resulting in glutamate release onto type I spiral ganglion neurons (SGNs) at specialized synapses known as "ribbon synapses". New findings published here in BMC Biology by Sonntag and colleagues indicate a role for the proteoglycan Brevican in forming perineurounal net (PNN) baskets at these synapses and controlling the spatial distribution of presynaptic voltage-gated calcium channels that regulate glutamate release. These findings may provide insight into the mechanism by which individual ribbon synapses within a single hair cell can function in an independent manner to facilitate hearing within a broad dynamic range.}, } @article {pmid30253753, year = {2018}, author = {Dong, Q and Mao, K and Duan, D and Zhao, S and Wang, Y and Wang, Q and Huang, D and Li, C and Liu, C and Gong, X and Ma, F}, title = {Genome-wide analyses of genes encoding FK506-binding proteins reveal their involvement in abiotic stress responses in apple.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {707}, pmid = {30253753}, issn = {1471-2164}, support = {31330068//the State Key Program of the National Natural Science Foundation of China/ ; CARS-27//the China Agriculture Research System/ ; 31401852//the National Natural Science Foundation of China/ ; 31701894//the National Natural Science Foundation of China/ ; }, mesh = {Amino Acid Sequence ; Conserved Sequence ; Exons ; Genes, Plant ; Genome, Plant ; Introns ; Malus/*genetics/metabolism ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Promoter Regions, Genetic ; Protein Conformation ; Protein Domains ; Protein Interaction Mapping ; Sequence Alignment ; Stress, Physiological ; Tacrolimus Binding Proteins/chemistry/*genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: The FK506-binding proteins (FKBPs) play diverse roles in numerous critical processes for plant growth, development, and abiotic stress responses. However, the FKBP gene family in the important fruit crop apple (Malus × domestica Borkh.) has not been studied as thoroughly as in other species. Our research objective was to investigate the mechanisms by which apple FKBPs enable apple plants to tolerate the effects of abiotic stresses.

RESULTS: Using bioinformatics-based methods, RT-PCR, and qRT-PCR technologies, we identified 38 FKBP genes and cloned 16 of them in the apple genome. The phylogenetic analysis revealed three major groups within that family. The results from sequence alignments, 3-D structures, phylogenetics, and analyses of conserved domains indicated that apple FKBPs are highly and structurally conserved. Furthermore, genomics structure analysis showed that those genes are also highly and structurally conserved in several other species. Comprehensive qRT-PCR analysis found various expression patterns for MdFKBPs in different tissues and in plant responses to water-deficit and salt stresses. Based on the results from interaction network and co-expression analyses, we determined that the pairing in the MdFKBP62a/MdFKBP65a/b-mediated network is involved in water-deficit and salt-stress signaling, both of which are uniformly up-regulated through interactions with heat shock proteins in apple.

CONCLUSIONS: These results provide new insight for further study of FKBP genes and their functions in abiotic stress response and multiple metabolic and physiological processes in apple.}, } @article {pmid30253752, year = {2018}, author = {Romero, JP and Ortiz-Estévez, M and Muniategui, A and Carrancio, S and de Miguel, FJ and Carazo, F and Montuenga, LM and Loos, R and Pío, R and Trotter, MWB and Rubio, A}, title = {Comparison of RNA-seq and microarray platforms for splice event detection using a cross-platform algorithm.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {703}, pmid = {30253752}, issn = {1471-2164}, support = {PRE_2016_1_0194//Eusko Jaurlaritza/ ; PI14/00806//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; PI14/00806//Secretaría de Estado de Investigacion, Desarrollo e Innovacion/ ; GCB14-2170//Fundación Científica Asociación Española Contra el Cáncer/ ; }, mesh = {*Algorithms ; *Alternative Splicing ; Cell Line, Tumor ; *Gene Expression Profiling ; Humans ; *Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; *Sequence Analysis, RNA ; }, abstract = {BACKGROUND: RNA-seq is a reference technology for determining alternative splicing at genome-wide level. Exon arrays remain widely used for the analysis of gene expression, but show poor validation rate with regard to splicing events. Commercial arrays that include probes within exon junctions have been developed in order to overcome this problem. We compare the performance of RNA-seq (Illumina HiSeq) and junction arrays (Affymetrix Human Transcriptome array) for the analysis of transcript splicing events. Three different breast cancer cell lines were treated with CX-4945, a drug that severely affects splicing. To enable a direct comparison of the two platforms, we adapted EventPointer, an algorithm that detects and labels alternative splicing events using junction arrays, to work also on RNA-seq data. Common results and discrepancies between the technologies were validated and/or resolved by over 200 PCR experiments.

RESULTS: As might be expected, RNA-seq appears superior in cases where the technologies disagree and is able to discover novel splicing events beyond the limitations of physical probe-sets. We observe a high degree of coherence between the two technologies, however, with correlation of EventPointer results over 0.90. Through decimation, the detection power of the junction arrays is equivalent to RNA-seq with up to 60 million reads.

CONCLUSIONS: Our results suggest, therefore, that exon-junction arrays are a viable alternative to RNA-seq for detection of alternative splicing events when focusing on well-described transcriptional regions.}, } @article {pmid30253751, year = {2018}, author = {Sanglard, LP and Nascimento, M and Moriel, P and Sommer, J and Ashwell, M and Poore, MH and Duarte, MS and Serão, NVL}, title = {Impact of energy restriction during late gestation on the muscle and blood transcriptome of beef calves after preconditioning.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {702}, pmid = {30253751}, issn = {1471-2164}, mesh = {Animal Nutritional Physiological Phenomena ; Animals ; Cattle/blood/*genetics/growth & development/metabolism ; Female ; Gene Regulatory Networks ; Male ; Muscle, Skeletal/*metabolism ; Pregnancy ; *Transcriptome ; }, abstract = {BACKGROUND: Maternal nutrition has been highlighted as one of the main factors affecting intra-uterine environment. The increase in nutritional requirements by beef cows during late gestation can cause nutritional deficiency in the fetus and impact the fetal regulation of genes associated with myogenesis and immune response.

METHODS: Forty days before the expected calving date, cows were assigned to one of two diets: 100% (control) or 70% (restricted group) of the daily energy requirement. Muscle samples were collected from 12 heifers and 12 steers, and blood samples were collected from 12 steers. The objective of this work was to identify and to assess the biological relevance of differentially expressed genes (DEG) in the skeletal muscle and blood of beef calves born from cows that experienced [or not] a 30% energy restriction during the last 40 days of gestation.

RESULTS: A total of 160, 164, and 346 DEG (q-value< 0.05) were identified in the skeletal muscle for the effects of diet, sex, and diet-by-sex interaction, respectively. For blood, 452, 1392, and 155 DEG were identified for the effects of diet, time, and diet-by-time interaction, respectively. For skeletal muscle, results based on diet identified genes involved in muscle metabolism. In muscle, from the 10 most DEG down-regulated in the energy-restricted group (REST), we identified 5 genes associated with muscle metabolism and development: SLCO3A1, ATP6V0D1, SLC2A1, GPC4, and RASD2. In blood, among the 10 most DEG, we found genes related to response to stress up-regulated in the REST after weaning, such as SOD3 and INO80D, and to immune response down-regulated in the REST after vaccination, such as OASL, KLRF1, and LOC104968634.

CONCLUSION: In conclusion, maternal energy restriction during late gestation may limit the expression of genes in the muscle and increase expression in the blood of calves. In addition, enrichment analysis showed that a short-term maternal energy restriction during pregnancy affects the expression of genes related to energy metabolism and muscle contraction, and immunity and stress response in the blood. Therefore, alterations in the intra-uterine environment can modify prenatal development with lasting consequences to adult life.}, } @article {pmid30253747, year = {2018}, author = {Cooper, CI and Yao, D and Sendorek, DH and Yamaguchi, TN and P'ng, C and Houlahan, KE and Caloian, C and Fraser, M and , and Ellrott, K and Margolin, AA and Bristow, RG and Stuart, JM and Boutros, PC}, title = {Valection: design optimization for validation and verification studies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {339}, pmid = {30253747}, issn = {1471-2105}, support = {New Investigator Award//Canadian Institutes of Health Research/Canada ; RS2014-01//Movember Foundation (AU)/ ; R01CA180778//National Cancer Institute/ ; New Investigator Award//Terry Fox Research Institute/ ; R01 CA180778/CA/NCI NIH HHS/United States ; }, mesh = {Sequence Analysis, DNA/*methods ; *Software Validation ; }, abstract = {BACKGROUND: Platform-specific error profiles necessitate confirmatory studies where predictions made on data generated using one technology are additionally verified by processing the same samples on an orthogonal technology. However, verifying all predictions can be costly and redundant, and testing a subset of findings is often used to estimate the true error profile.

RESULTS: To determine how to create subsets of predictions for validation that maximize accuracy of global error profile inference, we developed Valection, a software program that implements multiple strategies for the selection of verification candidates. We evaluated these selection strategies on one simulated and two experimental datasets.

CONCLUSIONS: Valection is implemented in multiple programming languages, available at: http://labs.oicr.on.ca/boutros-lab/software/valection.}, } @article {pmid30253740, year = {2018}, author = {Jieensinue, S and Zhu, H and Li, G and Dong, K and Liang, M and Li, Y}, title = {Tanshinone IIA reduces SW837 colorectal cancer cell viability via the promotion of mitochondrial fission by activating JNK-Mff signaling pathways.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {21}, pmid = {30253740}, issn = {1471-2121}, mesh = {Apoptosis/drug effects ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Colorectal Neoplasms/*metabolism/*pathology ; Diterpenes, Abietane/*pharmacology ; Humans ; MAP Kinase Signaling System/*drug effects ; Membrane Proteins/*metabolism ; Mitochondria/drug effects/metabolism/pathology ; Mitochondrial Dynamics/*drug effects ; Mitochondrial Proteins/*metabolism ; }, abstract = {BACKGROUND: Mitochondrial homeostasis has been increasingly viewed as a potential target of cancer therapy, and mitochondrial fission is a novel regulator of mitochondrial function and apoptosis. The aim of our study was to determine the detailed role of mitochondrial fission in SW837 colorectal cancer cell viability, mobility and proliferation. In addition, the current study also investigated the therapeutic impact of Tanshinone IIA (Tan IIA), a type of anticancer adjuvant drug, on cancer mitochondrial homeostasis.

RESULTS: The results of our data illustrated that Tan IIA promoted SW837 cell death, impaired cell migration and mediated cancer proliferation arrest in a dose-dependent manner. Functional investigation exhibited that Tan IIA treatment evoked mitochondrial injury, as witnessed by mitochondrial ROS overproduction, mitochondrial potential collapse, antioxidant factor downregulation, mitochondrial pro-apoptotic protein upregulation, and caspase-9-dependent apoptotic pathway activation. Furthermore, we confirmed that Tan IIA mediated mitochondrial damage by activating mitochondrial fission, and the inhibition of mitochondrial fission abrogated the proapoptotic effects of Tan IIA on SW837 cells. To this end, our results demonstrated that Tan IIA modulated mitochondrial fission via the JNK-Mff pathways. The blockade of the JNK-Mff axis inhibited Tan IIA-mediated mitochondrial fission and promoted the survival of SW837 cells.

CONCLUSIONS: Altogether, our results identified mitochondrial fission as a new potential target to control cancer viability, mobility and proliferation. Furthermore, our findings demonstrate that Tan IIA is an effective drug to treat colorectal cancer by activating JNK-Mff-mitochondrial fission pathways.}, } @article {pmid30253738, year = {2018}, author = {Pirone-Davies, C and Chen, Y and Pightling, A and Ryan, G and Wang, Y and Yao, K and Hoffmann, M and Allard, MW}, title = {Genes significantly associated with lineage II food isolates of Listeria monocytogenes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {708}, pmid = {30253738}, issn = {1471-2164}, mesh = {Disease Outbreaks ; *Food Microbiology ; Genes, Bacterial ; Humans ; Listeria monocytogenes/classification/*genetics/isolation & purification/pathogenicity ; Listeriosis/epidemiology/microbiology ; Polymorphism, Single Nucleotide ; Serogroup ; Stress, Physiological/genetics ; Virulence/genetics ; }, abstract = {BACKGROUND: Listeria monocytogenes is a widespread foodborne pathogen that can cause listeriosis, a potentially fatal infection. L. monocytogenes is subdivided into four phylogenetic lineages, with the highest incidence of listeriosis occurring within lineage I followed by lineage II. Strains of L. monocytogenes differ in their phenotypic characteristics, including virulence. However, the genetic bases for these observed differences are not well understood, and current efforts to monitor L. monocytogenes in food consider all strains to be equally virulent. We use a comparative genomics approach to identify genes and single nucleotide polymorphisms (SNPs) in 174 clinical and food isolates of L. monocytogenes that potentially contribute to virulence or the capacity to adapt to food environments.

RESULTS: No SNPs are significantly associated with food or clinical isolates. No genes are significantly associated with food or clinical isolates from lineage I, but eight genes consisting of multiple homologues are associated with lineage II food isolates. These include three genes which encode hypothetical proteins, the cadmium resistance genes cadA and cadC, the multi-drug resistance gene ebrB, a quaternary ammonium compound resistance gene qac, and a regulatory gene. All eight genes are plasmid-borne, and most closed L. monocytogenes plasmids carry at least five of the genes (24/27). In addition, plasmids are more frequently associated with lineage II food isolates than with lineage II clinical isolates.

CONCLUSIONS: We identify eight genes that are significantly associated with food isolates in lineage II. Interestingly, the eight genes are virtually absent in lineage II outbreak isolates, are composed of homologues which show a nonrandom distribution among lineage I serotypes, and the sequences are highly conserved across 27 closed Listeria plasmids. The functions of these genes should be explored further and will contribute to our understanding of how L. monocytogenes adapts to the host and food environments. Moreover, these genes may also be useful as markers for risk assessment models of either pathogenicity or the ability to proliferate in food and the food processing environment.}, } @article {pmid30253736, year = {2018}, author = {Wu, Y and Ma, X and Pan, Z and Kale, SD and Song, Y and King, H and Zhang, Q and Presley, C and Deng, X and Wei, CI and Xiao, S}, title = {Comparative genome analyses reveal sequence features reflecting distinct modes of host-adaptation between dicot and monocot powdery mildew.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {705}, pmid = {30253736}, issn = {1471-2164}, support = {IOS-1457033//National Science Foundation/ ; 2955660//Institute for bioscience and biotechnology research/ ; 2955310//Maryland Agricultural Experiment Station/ ; 2956830//Maryland Agricultural Experiment Station/ ; }, mesh = {Adaptation, Physiological ; Ascomycota/classification/*genetics/pathogenicity ; Gene Deletion ; Gene Expression Profiling ; Genes, Fungal ; Genome Size ; *Genome, Fungal ; High-Throughput Nucleotide Sequencing ; Host Specificity/*genetics ; Mycelium/genetics/metabolism ; Mycological Typing Techniques ; Plant Diseases/*microbiology ; Poaceae/microbiology ; }, abstract = {BACKGROUND: Powdery mildew (PM) is one of the most important and widespread plant diseases caused by biotrophic fungi. Notably, while monocot (grass) PM fungi exhibit high-level of host-specialization, many dicot PM fungi display a broad host range. To understand such distinct modes of host-adaptation, we sequenced the genomes of four dicot PM biotypes belonging to Golovinomyces cichoracearum or Oidium neolycopersici.

RESULTS: We compared genomes of the four dicot PM together with those of Blumeria graminis f.sp. hordei (both DH14 and RACE1 isolates), B. graminis f.sp. tritici, and Erysiphe necator infectious on barley, wheat and grapevine, respectively. We found that despite having a similar gene number (6620-6961), the PM genomes vary from 120 to 222 Mb in size. This high-level of genome size variation is indicative of highly differential transposon activities in the PM genomes. While the total number of genes in any given PM genome is only about half of that in the genomes of closely related ascomycete fungi, most (~ 93%) of the ascomycete core genes (ACGs) can be found in the PM genomes. Yet, 186 ACGs were found absent in at least two of the eight PM genomes, of which 35 are missing in some dicot PM biotypes, but present in the three monocot PM genomes, indicating remarkable, independent and perhaps ongoing gene loss in different PM lineages. Consistent with this, we found that only 4192 (3819 singleton) genes are shared by all the eight PM genomes, the remaining genes are lineage- or biotype-specific. Strikingly, whereas the three monocot PM genomes possess up to 661 genes encoding candidate secreted effector proteins (CSEPs) with families containing up to 38 members, all the five dicot PM fungi have only 116-175 genes encoding CSEPs with limited gene amplification.

CONCLUSIONS: Compared to monocot (grass) PM fungi, dicot PM fungi have a much smaller effectorome. This is consistent with their contrasting modes of host-adaption: while the monocot PM fungi show a high-level of host specialization, which may reflect an advanced host-pathogen arms race, the dicot PM fungi tend to practice polyphagy, which might have lessened selective pressure for escalating an with a particular host.}, } @article {pmid30253735, year = {2018}, author = {Reig-Valiente, JL and Marqués, L and Talón, M and Domingo, C}, title = {Genome-wide association study of agronomic traits in rice cultivated in temperate regions.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {706}, pmid = {30253735}, issn = {1471-2164}, support = {RTA2014-00058-C03-00//Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria/ ; 01/14-FSE-0//European Social Fund/ ; IDI-20170652//Dirección General de Investigación Científica y Técnica/ ; }, mesh = {Agriculture ; Climate ; Genome-Wide Association Study ; Oryza/anatomy & histology/*genetics ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; }, abstract = {BACKGROUND: Rice plants are sensitive to the agro-climate conditions, being photoperiod one of main factor contributing to their adaptation to the region where they are grown. Dissecting the genetic bases underlying diversity in rice populations adapted to specific environmental conditions is a fundamental resource for breeding. In this study we have analysed a collection of japonica varieties adapted to temperate regions to perform association studies with traits of high agronomical interest such as heading date, plant height, number of panicles, panicle length and number of grains per panicle.

RESULTS: We have performed a genome wide association study using a panel of 1713 SNPs that, based on previous linkage disequilibrium estimations, provides a full coverage of the whole genome. We have found a total of 43 SNPs associated with variations in the different traits. The identified SNPs were distributed across the genome except in chromosome 12, where no associated SNPs were found. The inspection of the vicinity of these markers also revealed a set of genes associated with physiological functions strongly linked to agronomic traits. Of special relevance are two genes involved in gibberellin homeostasis that are associated with plant height and panicle length. We also detected novel associated sites with heading date, panicle length and number of grain per panicle.

CONCLUSION: We have identified loci associated with important agronomic traits among cultivars adapted to temperate conditions. Some of these markers co-localized with already known genes or QTLs, but the association also provided novel molecular markers that can be of help to elucidate the complicated genetic mechanism controlling important agronomic traits, as flowering regulation in the non-dependent photoperiod pathway. The detected associated markers may provide important tools for the genetic improvement of rice cultivars in temperate regions.}, } @article {pmid30253734, year = {2018}, author = {Arenas Gómez, CM and Woodcock, RM and Smith, JJ and Voss, RS and Delgado, JP}, title = {Using transcriptomics to enable a plethodontid salamander (Bolitoglossa ramosi) for limb regeneration research.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {704}, pmid = {30253734}, issn = {1471-2164}, support = {569(027-2013)//Departamento Administrativo de Ciencia, Tecnología e Innovación/ ; 567//Departamento Administrativo de Ciencia, Tecnología e Innovación/ ; sostenibilidad//Universidad de Antioquia/ ; R24OD010435//National Institutes of Health/ ; R24 OD010435/OD/NIH HHS/United States ; W911NF1410165//Army Research Office/ ; }, mesh = {Animals ; Extremities/*physiology ; *Gene Expression Profiling ; Models, Animal ; Real-Time Polymerase Chain Reaction ; Regeneration/*genetics ; Urodela/*genetics ; }, abstract = {BACKGROUND: Tissue regeneration is widely distributed across the tree of life. Among vertebrates, salamanders possess an exceptional ability to regenerate amputated limbs and other complex structures. Thus far, molecular insights about limb regeneration have come from a relatively limited number of species from two closely related salamander families. To gain a broader perspective on the molecular basis of limb regeneration and enhance the molecular toolkit of an emerging plethodontid salamander (Bolitoglossa ramosi), we used RNA-Seq to generate a de novo reference transcriptome and identify differentially expressed genes during limb regeneration.

RESULTS: Using paired-end Illumina sequencing technology and Trinity assembly, a total of 433,809 transcripts were recovered and we obtained functional annotation for 142,926 non-redundant transcripts of the B. ramosi de novo reference transcriptome. Among the annotated transcripts, 602 genes were identified as differentially expressed during limb regeneration. This list was further processed to identify a core set of genes that exhibit conserved expression changes between B. ramosi and the Mexican axolotl (Ambystoma mexicanum), and presumably their common ancestor from approximately 180 million years ago.

CONCLUSIONS: We identified genes from B. ramosi that are differentially expressed during limb regeneration, including multiple conserved protein-coding genes and possible putative species-specific genes. Comparative analyses reveal a subset of genes that show similar patterns of expression with ambystomatid species, which highlights the importance of developing comparative gene expression data for studies of limb regeneration among salamanders.}, } @article {pmid30253028, year = {2018}, author = {McNair, HM and Brzezinski, MA and Krause, JW}, title = {Diatom populations in an upwelling environment decrease silica content to avoid growth limitation.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4184-4193}, pmid = {30253028}, issn = {1462-2920}, support = {S10 OD010610/OD/NIH HHS/United States ; 1 S10 OD010610-01A1//National Institutes of Health/ ; OCE-1155663//National Science Foundation/ ; OD010610-01A1//National Science Foundation/ ; }, abstract = {A mix of adaptive strategies enable diatoms to sustain rapid growth in dynamic ocean regions, making diatoms one of the most productive primary producers in the world. We illustrate one such strategy off coastal California that facilitates continued, high, cell division rates despite silicic acid stress. Using a fluorescent dye to measure single-cell diatom silica production rates, silicification (silica per unit area) and growth rates we show diatoms decrease silicification and maintain growth rate when silicon concentration limits silica production rates. While this physiological response to silicon stress was similar across taxa, in situ silicic acid concentration limited silica production rates by varying degrees for taxa within the same community. Despite this variability among taxa, silicon stress did not alter the contribution of specific taxa to total community silica production or to community composition. Maintenance of division rate at the expense of frustule thickness decreases cell density which could affect regional biogeochemical cycles. The reduction in frustule silicification also creates an ecological tradeoff: thinner frustules increase susceptibility to predation but reducing Si quotas maximizes cell abundance for a given pulse of silicic acid, thereby favouring a larger eventual population size which facilitates diatom persistence in habitats with pulsed resource supplies.}, } @article {pmid30252927, year = {2018}, author = {Vicenti, I and Rossetti, B and Mariano, S and Saladini, F and Montagnani, F and Zazzi, M and De Luca, A}, title = {Distribution of different HBV DNA forms in plasma and peripheral blood mononuclear cells (PBMCs) of chronically infected patients with low or undetectable HBV plasma viremia.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {302-305}, pmid = {30252927}, issn = {1121-7138}, abstract = {Few studies have documented hepatitis B virus (HBV) DNA in peripheral blood mononuclear cells (PBMCs). We developed real-time PCR methods for differential amplification of covalently closed circular (cccDNA) and total HBV DNA (tDNA). The different distribution of cccDNA and tDNA in plasma and PBMCs was evaluated in 37 patients with low or undetectable viremia. Plasma tDNA measured by the Abbott reference system and the in-house assay correlated well (Spearman rho = 0.804; P<0.0001). tDNA was detected in four PBMC samples, all from patients with detectable plasma viremia (range 633-6,406 IU/ml), cccDNA was not detected in any sample. The reasons for apparently discrepant results need further investigation but possibly include the high diversification of HBV status and plasma viremia levels.}, } @article {pmid30252926, year = {2019}, author = {Schepisi, MS and Motta, I and Dore, S and Costa, C and Sotgiu, G and Girardi, E}, title = {Tuberculosis transmission among children and adolescents in schools and other congregate settings: a systematic review.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {282-290}, pmid = {30252926}, issn = {1121-7138}, abstract = {Children, especially those aged <5 years, and adolescents are at increased risk of progression to active TB disease when infected. Management of childhood TB outbreaks is crucial for TB elimination especially in low burden countries. We searched the electronic databases MEDLINE-CINHAL-EMBASE up to July 2017 for primary studies reporting on TB incidents which involved teacher/child-caregiver, relative or students diagnosed with TB in a school/childcare setting or in other congregate settings attended by children and adolescents. Out of 10,481 citations, 74 studies, published mostly in low TB burden countries from 1950 to 2017, describing 128 incident investigations, were included. Overall 5025 (14.2%) LTBI and 811 (2.3%) TB cases were diagnosed among 35,331 screened individuals. Incidents occurred mainly in schools (89.1%) where index cases were more frequently students (63.3%) than teachers/caregivers; almost all of the incidents exposing children aged 2-5 were attributable to a teacher/caregiver index case. In 68 individual contact investigations the pooled proportions of TB and LTBI among those exposed were 0.03 (95%CI 0.02-0.04) and 0.15 (95%CI 0.13- 0.18). The overall risk of developing TB disease in school-congregate settings seems slightly lower than in high-income country household settings. Public health interventions targeting school-congregate settings may be critical to overall TB control and towards TB elimination in low-burden countries.}, } @article {pmid30252925, year = {2018}, author = {Ferranti, M and Schiaroli, E and Palmieri, MI and Repetto, A and Vecchiarelli, A and Francisci, D and Mencacci, A and Monari, C}, title = {Carbapenemase-producing Enterobacteriaceae isolates resistant to last-line antibiotics in an Italian general hospital.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {274-281}, pmid = {30252925}, issn = {1121-7138}, abstract = {The global dissemination of carbapenemase-producing Enterobacteriaceae (CPE) is of great concern for public health. These bacteria have the potential for rapid dissemination in healthcare settings and cause infections associated with high rates of morbidity and mortality. A total of 221 carbapenem non-susceptible Enterobacteriaceae isolates were collected from patients admitted to an Italian general hospital from January 2016 to March 2017. Among these isolates, 78.3% were carbapenemase producers: 96% were positive for the blaKPC gene and the remainder for the blaVIM gene (allelic variant VIM-1). CPE isolates were mainly Klebsiella pneumoniae, but we also detected carbapenemase enzymes in Citrobacter freundii, Enterobacter cloacae and Escherichia coli. Among CPE isolates, 79.2% exhibited co-resistance to two or more non-b-lactam agents and 38% of these isolates (all KPC-positive) were resistant to colistin. This percentage reached 55% among CPE isolated from the bloodstream. All patients with colistin-resistant CPE isolates recovered from blood samples showed an unfavorable outcome within 7 days from the first positive blood culture. Our data show the dissemination of a high percentage of CPE isolates co-resistant to last-line antibiotics. In addition, we report the first identification in our hospital of CPE isolates harboring the blaVIM gene and Escherichia coli harboring the blaKPC gene. These results underline the need to implement antibiotic stewardship and infection control programs, and emphasize the need for novel antimicrobial agents active against CPE.}, } @article {pmid30252924, year = {2018}, author = {Mascellino, MT and Oliva, A and De Angelis, M and Pontone, S and Porowska, B}, title = {Helicobacter pylori infection: antibiotic resistance and eradication rate in patients with gastritis showing previous treatment failures.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {306-309}, pmid = {30252924}, issn = {1121-7138}, abstract = {Forty patients infected by Helicobacter pylori were studied. The treatment was based on the positivity or negativity of cultures (tailored therapy or empiric therapy). The eradication rate was 68% and 82% respectively. Genotypic susceptibility testing proved very useful in case of heteroresistance or mixed infections that represent a real problem possibly leading to a resistance underestimation. Real-time PCR detected the resistant population at a very low concentration not detectable by phenotypic tests. Bismuth quadruple therapy (PPI, bismuth, metronidazole, tetracycline, PBMT) was effective in the Hp eradication rate consistent with a high level of clarithromycin resistance.}, } @article {pmid30252923, year = {2018}, author = {Galizzi, N and Galli, L and Poli, A and Spagnuolo, V and Castagna, A and Gianotti, N}, title = {Glomerular filtration rate estimated by cystatin C formulas in HIV-1 patients treated with dolutegravir, rilpivirine or cobicistat.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {256-261}, pmid = {30252923}, issn = {1121-7138}, abstract = {As dolutegravir (DTG), rilpivirine (RPV) and cobicistat affect creatinine, but not cystatin C, tubular transport or serum concentration, the aim of the study was to compare estimated glomerular filtration rates (eGFRs) calculated by means of a standard creatinine formula with those calculated by means of the cystatin C formula in patients receiving these drugs. This was a cross-sectional study of HIV-1 infected patients with eGFR <90 ml/min/1.73 m2 (CKD-EPI-creatinine formula) on-treatment with regimens including DTG, RVP or cobicistat; cystatin C was measured after the switch to these regimens. eGFR was calculated by means of the CKD-EPI formulas (CKD-EPI-creatinine: eGFRcrea; CKD-EPI-cystatin C: eGFRcyst). eGFRcyst was compared with the last eGFR assessed before (eGFRcrea pre) and after the switch (eGFRcrea post). The primary end-point of the study was the difference between eGFRcyst and eGFRcrea post. One hundred and twenty patients were included. eGFRcrea pre was 80 (70-92) ml/min/1.73 m2. eGFRcrea post was significantly lower than eGFRcyst (65 [59-75] vs. 80 [69-95] mL/ min/1.73m2; p<0.001); eGFRcyst did not differ from eGFRcrea pre (p=0.544). The difference between eGFRcyst and eGFRcrea post was not significantly different among regimen groups (p=0.056). In HIV-patients with reduced eGFR treated with DTG, RPV or cobicistat, measuring eGFR by means of the CKD-EPI cystatin C formula is probably more relevant.}, } @article {pmid30252922, year = {2018}, author = {Fusco, FM and Vichi, F and Bisanzi, S and Sani, C and Degli Esposti, A and Blè, C and Rossi, R and Pompeo, G and Carozzi, F and Blanc, P}, title = {HPV infection and pre-neoplastic cervical lesions among 321 HIV+ women in Florence, Italy, 2006-2016: prevalence and associated factors.}, journal = {The new microbiologica}, volume = {41}, number = {4}, pages = {268-273}, pmid = {30252922}, issn = {1121-7138}, abstract = {Women living with HIV (WLWH) are at higher risk for HPV-related malignancies. To estimate the factors associated to HPV infection and to pre-neoplastic cervical lesions, we observed 321 WLWH in an HIV care-centre in Florence, Italy. In 2006-2016, WLWH followed at S. Maria Annunziata Hospital underwent to gynaecological examination including HPV-test, Pap-smear, colposcopy and, if needed, cervical biopsy. Demographical and clinical information were collected and linear logistic regression was performed. Among 321 WLWH, 161 (50.2%) resulted HPV+. Multiple genotypes were identified in 35%, and cancer high-risk genotypes in 61%. Younger age, not-caucasic origin, increasing number of partners, and shorter duration of HIV are associated with HPV infection. A colposcopy was performed in 154 HIV+/HPV+ women: histological lesions were present in 47 (30%). Among these, CIN1, CIN2 and CIN3 were present in 16, 4, and 1 patients, respectively. Being caucasic, smoking 1-20 cigarettes/day, having 2 partners in the last year, and being an injective-drug-user are associated with cervical lesions. The use of bi-valent, 4-valent and 9-valent HPV vaccines would potentially prevent lesions in 19%, 33%, and 48%. Among WLWH efficaciously in care for HIV, demographic and behavioral factors mainly contribute to acquisition of HPV and to development of cervical lesions.}, } @article {pmid30252645, year = {2018}, author = {Kaewkrajay, C and Limtong, S}, title = {Spencerozyma siamensis sp. nov., a novel anamorphic basidiomycetous yeast species in Puccinomycotina isolated from coral in Thailand.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3611-3614}, doi = {10.1099/ijsem.0.003043}, pmid = {30252645}, issn = {1466-5034}, mesh = {Animals ; Anthozoa/*microbiology ; Basidiomycota/*classification/genetics/isolation & purification ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Mycological Typing Techniques ; *Phylogeny ; Sequence Analysis, DNA ; Thailand ; }, abstract = {Strain DMKU13-2T, representing a novel anamorphic yeast species in the class Microbotryomycetes, subphylum Puccinomycotina, phylum Basidiomycota, was isolated from a soft coral collected in the sea off Ko Mu island, Thailand. The phylogenetic analysis based on the concatenated sequences of the internal transcribed spacer (ITS) region and the D1/D2 region of the large subunit ribosomal RNA (LSU rRNA) gene indicated that this strain was a novel species in the genus Spencerozyma and distant from Spencerozyma crocea, the only species of the genus. The novel species differed from the type of S. crocea (CBS 2029T) by 5.2 % nucleotides (31 nucleotide substitutions out of 594 bp) in the D1/D2 region of the LSU rRNA gene and 9.0 % nucleotides (66 nucleotide substitutions out of 735 bp) in the ITS region. The name Spencerozyma siamensis sp. nov. is proposed. The type is DMKU13-2T (=CBS 14683=TBRC 7039). The MycoBank number is MB 824889.}, } @article {pmid30252644, year = {2018}, author = {Park, C and Lee, YS and Park, SY and Park, W}, title = {Methylobacterium currus sp. nov., isolated from a car air conditioning system.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3621-3626}, doi = {10.1099/ijsem.0.003045}, pmid = {30252644}, issn = {1466-5034}, mesh = {*Air Conditioning ; *Automobiles ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Methylobacterium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A novel bacterial strain, designated PR1016AT, was isolated from a car air conditioning system. This rod-shaped strain showed catalase and oxidase activities, was aerobic and methylotrophic, and had a reddish pink colour. The genomic DNA G+C content of strain PR1016AT was 70.2 mol%, as determined by genome sequencing. Phylogenetic analysis based on 16S rRNA gene sequence similarity showed that strain PR1016AT was most closely related to Methylobacterium aquaticum GR16T (98.86 %), M. variabile GR3T (98.43 %), M. platani PMB 02T (98.36 %) and M. tarhaniae N4211T (98.14 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain PR1016AT and M. aquaticum GR16T, M. platani PMB02T and M. variabile GR3T were 88.61, 88.14 and 87.88 %, and 36.4, 35.8 and 34.7 %, respectively. Numerous insertion sequences are present in the genome of strain PR1016AT, which has a larger genome than the four Methylobacterium species described above. Cells grew at 18-42 °C (optimum, 30 °C), at pH 4.0-9.0 (optimum, pH 7.0) and in the presence of 0-1.0 % (w/v) NaCl (optimum, 0 %). The major respiratory quinone was Q10. Fatty acid methyl ester analysis revealed that summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) was the predominant cellular fatty acid in strain PR1016AT. Two-dimensional TLC indicated that the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and phosphatidylcholine. The genotypic and phenotypic characteristics indicate that strain PR1016AT represents a novel species of the genus Methylobacterium, for which the name Methylobacterium currus sp. nov. is proposed. The type strain is PR1016AT (=KACC 19662T=JCM 32670T).}, } @article {pmid30252641, year = {2018}, author = {Chen, L and Chen, WF and Xu, ZL and Li, W and Zhang, XY and Li, WJ and Wang, L}, title = {Sphingomonas oleivorans sp. nov., isolated from oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3720-3725}, doi = {10.1099/ijsem.0.003014}, pmid = {30252641}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Petroleum Pollution ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; *Soil Pollutants ; Sphingomonas/*classification/genetics/isolation & purification ; Ubiquinone/chemistry ; }, abstract = {Strain FW-11T was isolated from oil-contaminated soil from Panjin in Liaoning, China. It was a Gram-stain-negative, aerobic and rod-shaped bacterium. The strain was confirmed to be a member of the genus Sphingomonas based on phylogenetic inference and phenotypic characteristics. The best growth of strain FW-11T occurred at 30 °C and pH 6.0-7.0. The strain was non-spore-forming, catalase-negative and oxidase-negative. The main polar lipids were sphingoglycolipid, phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and unidentified lipids. The cell-wall peptidoglycan of strain FW-11T included alanine, glycine, glutamic acid, aspartic acid and meso-diaminopimelate. The predominant isoprenoid quinones were ubiquinone Q-10 (93.2 %) and Q-9 (6.8 %). The fatty acid profile (>5 %) included C18 : 1ω6c (43.1 %), C16 : 0 (14.6 %), C17 : 1ω6c (14.0 %) and C14 : 0 2-OH (11.1 %). The most similar neighbours of FW-11T were Sphingomonas fennica K101T (97.4 %) and Sphingomonas haloaromaticamans A175T (97.0 %). The average nucleotide identity relatedness values between strain FW-11T and the two type strains (S. fennica K101T and S. haloaromaticamans A175T) were 73.2 and 75.3 %, respectively. The genome size of FW-11T was 3.8 Mbp, comprising 3735 predicted genes with a DNA G+C content of 64.0 mol%. Based on phenotypic, chemotaxonomic and phylogenetic data, strain FW-11T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas oleivorans sp. nov. is proposed. The type strain is FW-11T (=LMG 29274T=HAMBI 3659T).}, } @article {pmid30252640, year = {2018}, author = {Yan, XR and Tuo, L}, title = {Paenibacillus paeoniae sp. nov., a novel endophytic bacterium isolated from leaf of Paeonia lactiflora Pall.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3606-3610}, doi = {10.1099/ijsem.0.003042}, pmid = {30252640}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Endophytes/classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Paenibacillus/*classification/genetics/isolation & purification ; Paeonia/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Plant Leaves/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, aerobic, rod-shaped, endospore-forming bacterium, designated strain M4BSY-1T, was originally isolated from a surface-sterilized leaf of Paeonia lactiflora Pall. in Guizhou, China. The bacterium was characterized by a polyphasic approach to determine its taxonomic position. 16S rRNA gene sequence comparison revealed that strain M4BSY-1T belongs to the genus Paenibacillus and most closely to Paenibacilluspinioli NB5T (98.31 % similarity). Neither substrate nor aerial mycelia formed, and no diffusible pigments were observed on the media tested. Strain M4BSY-1T grew in the pH range 7.0-13.0 (optimum, 7.0-8.0), at temperatures between 10-37 °C (optimum, 30 °C) and at 0-5 % (w/v) NaCl (optimum, 1-2 %). The predominant menaquinone was MK-7. The major fatty acids were anteiso-C15 : 0, C16 : 0 and iso-C16 : 0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified unknown aminophospholipids and three unidentified phospholipids. The DNA G+C content was 48.8 mol%. According to the phylogenetic, phenotypic and chemotaxonomic evidence, strain M4BSY-1T was clearly distinguishable from other species with validly published names in the genus Paenibacillus and should therefore be classified as a novel species, and we suggest the name Paenibacillus paeoniae sp. nov. The type strain is M4BSY-1T (=KCTC 33997T=CGMCC 1.13667T).}, } @article {pmid30252211, year = {2019}, author = {Gambari, C and Boyeldieu, A and Armitano, J and Méjean, V and Jourlin-Castelli, C}, title = {Control of pellicle biogenesis involves the diguanylate cyclases PdgA and PdgB, the c-di-GMP binding protein MxdA and the chemotaxis response regulator CheY3 in Shewanella oneidensis.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {81-97}, doi = {10.1111/1462-2920.14424}, pmid = {30252211}, issn = {1462-2920}, support = {//Aix-Marseille Université/ ; //Centre National de la Recherche Scientifique/ ; Grant N°152 660//HTS-BIO/ ; }, abstract = {Shewanella oneidensis is an aquatic proteobacterium with remarkable respiratory and chemotactic abilities. It is also capable of forming biofilms either associated to surfaces (SSA-biofilm) or at the air-liquid interface (pellicle). We have previously shown that pellicle biogenesis in S. oneidensis requires the flagellum and the chemotaxis regulatory system including CheA3 kinase and CheY3 response regulator. Here we searched for additional factors involved in pellicle development. Using a multicopy library of S. oneidensis chromosomal fragments, we identified two genes encoding putative diguanylate cyclases (pdgA and pdgB) and allowing pellicle formation in the non-pellicle-forming cheY3-deleted mutant. A mutant deleted of both pdgA and pdgB is affected during pellicle development. By overexpressing phosphodiesterase encoding genes, we confirmed the key role of c-di-GMP in pellicle biogenesis. The mxd operon, previously proposed to encode proteins involved in exopolysaccharide biosynthesis, is also essential for pellicle formation. In addition, we showed that the MxdA protein, containing a degenerate GGDEF motif, binds c-di-GMP and interacts with both CheY3 and PdgA. Therefore, we propose that pellicle biogenesis in S. oneidensis is controlled by a complex pathway that involves the chemotaxis response regulator CheY3, the two putative diguanylate cyclases PdgA and PdgB, and the c-di-GMP binding protein MxdA.}, } @article {pmid30252196, year = {2018}, author = {Kim, SK and Park, SJ and Li, XH and Choi, YS and Im, DS and Lee, JH}, title = {Bacterial ornithine lipid, a surrogate membrane lipid under phosphate-limiting conditions, plays important roles in bacterial persistence and interaction with host.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3992-4008}, doi = {10.1111/1462-2920.14430}, pmid = {30252196}, issn = {1462-2920}, support = {NRF-2016R1A2B4014963//National Research Foundation of Korea/ ; }, abstract = {Ornithine lipids (OLs) are bacteria-specific lipids that are found in the outer membrane of Gram (-) bacteria and increase as surrogates of phospholipids under phosphate-limited environmental conditions. We investigated the effects of OL increase in bacterial membranes on pathogen virulence and the host immune response. In Pseudomonas aeruginosa, we increased OL levels in membranes by overexpressing the OL-synthesizing operon (olsBA). These increases changed the bacterial surface charge and hydrophobicity, which reduced bacterial susceptibility to antibiotics and antimicrobial peptides (AMPs), interfered with the binding of macrophages to bacterial cells and enhanced bacterial biofilm formation. When grown under low phosphate conditions, P. aeruginosa became more persistent in the treatment of antibiotics and AMPs in an olsBA-dependent manner. While OLs increased persistence, they attenuated P. aeruginosa virulence; in host cells, they reduced the production of inflammatory factors (iNOS, COX-2, PGE2 and nitric oxide) and increased intracellular Ca2+ release. Exogenously added OL had similar effects on P. aeruginosa and host cells. Our results suggest that bacterial OL plays important roles in bacteria-host interaction in a way that enhances bacterial persistence and develops chronic adaptation to infection.}, } @article {pmid30252115, year = {2018}, author = {Glenfield, C and McLysaght, A}, title = {Pseudogenes Provide Evolutionary Evidence for the Competitive Endogenous RNA Hypothesis.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2886-2899}, pmid = {30252115}, issn = {1537-1719}, support = {309834//European Research Council/International ; }, abstract = {The competitive endogenous RNA (ceRNA) hypothesis is an attractively simple model to explain the biological role of many putatively functionless noncoding RNAs. Under this model, there exist transcripts in the cell whose role is to titrate out microRNAs such that the expression level of another target sequence is altered. That it is logistically possible for expression of one microRNA recognition element (MRE)-containing transcript to affect another is seen in the multiple examples of pathogenic effects of inappropriate expression of MRE-containing RNAs. However, the role, if any, of ceRNAs in normal biological processes and at physiological levels is disputed. By comparison of parent genes and pseudogenes we show, both for a specific example and genome-wide, that the pseudo-3' untranslated regions (3'UTRs) of expressed pseudogenes are frequently retained and are under selective constraint in mammalian genomes. We found that the pseudo-3'UTR of BRAFP1, a previously described oncogenic ceRNA, has reduced substitutions relative to its pseudo-coding sequence, and we show sequence constraint on MREs shared between the parent gene, BRAF, and the pseudogene. Investigation of RNA-seq data reveals expression of BRAFP1 in normal somatic tissues in human and in other primates, consistent with biological ceRNA functionality of this pseudogene in nonpathogenic cellular contexts. Furthermore, we find that on a genome-wide scale pseudo-3'UTRs of mammalian pseudogenes (n = 1,629) are under stronger selective constraint than their pseudo-coding sequence counterparts, and are more often retained and expressed. Our results suggest that many human pseudogenes, often considered nonfunctional, may have an evolutionarily constrained role, consistent with the ceRNA hypothesis.}, } @article {pmid30252081, year = {2018}, author = {Suzuki, H and Nishida, H and Kondo, H and Yoda, R and Iwata, T and Nakayama, K and Enomoto, T and Wu, J and Moriya-Ito, K and Miyazaki, M and Wakabayashi, Y and Kishida, T and Okabe, M and Suzuki, Y and Ito, T and Hirota, J and Nikaido, M}, title = {A Single Pheromone Receptor Gene Conserved across 400 My of Vertebrate Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2928-2939}, doi = {10.1093/molbev/msy186}, pmid = {30252081}, issn = {1537-1719}, abstract = {Pheromones are crucial for eliciting social and sexual behaviors in diverse animal species. The vomeronasal receptor type-1 (V1R) genes, encoding members of a pheromone receptor family, are highly variable in number and repertoire among mammals due to extensive gene gain and loss. Here, we report a novel pheromone receptor gene belonging to the V1R family, named ancient V1R (ancV1R), which is shared among most Osteichthyes (bony vertebrates) from the basal lineage of ray-finned fishes to mammals. Phylogenetic and syntenic analyses of ancV1R using 115 vertebrate genomes revealed that it represents an orthologous gene conserved for >400 My of vertebrate evolution. Interestingly, the loss of ancV1R in some tetrapods is coincident with the degeneration of the vomeronasal organ in higher primates, cetaceans, and some reptiles including birds and crocodilians. In addition, ancV1R is expressed in most mature vomeronasal sensory neurons in contrast with canonical V1Rs, which are sparsely expressed in a manner that is consistent with the "one neuron-one receptor" rule. Our results imply that a previously undescribed V1R gene inherited from an ancient Silurian ancestor may have played an important functional role in the evolution of vertebrate vomeronasal organ.}, } @article {pmid30252076, year = {2018}, author = {Bailey, SF and Guo, Q and Bataillon, T}, title = {Identifying Drivers of Parallel Evolution: A Regression Model Approach.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2801-2812}, pmid = {30252076}, issn = {1759-6653}, abstract = {Parallel evolution, defined as identical changes arising in independent populations, is often attributed to similar selective pressures favoring the fixation of identical genetic changes. However, some level of parallel evolution is also expected if mutation rates are heterogeneous across regions of the genome. Theory suggests that mutation and selection can have equal impacts on patterns of parallel evolution; however, empirical studies have yet to jointly quantify the importance of these two processes. Here, we introduce several statistical models to examine the contributions of mutation and selection heterogeneity to shaping parallel evolutionary changes at the gene-level. Using this framework, we analyze published data from forty experimentally evolved Saccharomyces cerevisiae populations. We can partition the effects of a number of genomic variables into those affecting patterns of parallel evolution via effects on the rate of arising mutations, and those affecting the retention versus loss of the arising mutations (i.e., selection). Our results suggest that gene-to-gene heterogeneity in both mutation and selection, associated with gene length, recombination rate, and number of protein domains drive parallel evolution at both synonymous and nonsynonymous sites. While there are still a number of parallel changes that are not well described, we show that allowing for heterogeneous rates of mutation and selection can provide improved predictions of the prevalence and degree of parallel evolution.}, } @article {pmid30252073, year = {2018}, author = {Kelleher, ES and Azevedo, RBR and Zheng, Y}, title = {The Evolution of Small-RNA-Mediated Silencing of an Invading Transposable Element.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {3038-3057}, doi = {10.1093/gbe/evy218}, pmid = {30252073}, issn = {1759-6653}, abstract = {Transposable elements (TEs) are genomic parasites that impose fitness costs on their hosts by producing deleterious mutations and disrupting gametogenesis. Host genomes avoid these costs by regulating TE activity, particularly in germline cells where new insertions are heritable and TEs are exceptionally active. However, the capacity of different TE-associated fitness costs to select for repression in the host, and the role of selection in the evolution of TE regulation more generally remain controversial. In this study, we use forward, individual-based simulations to examine the evolution of small-RNA-mediated TE regulation, a conserved mechanism for TE repression that is employed by both prokaryotes and eukaryotes. To design and parameterize a biologically realistic model, we drew on an extensive survey of empirical studies of the transposition and regulation of P-element DNA transposons in Drosophila melanogaster. We observed that even under conservative assumptions, where small-RNA-mediated regulation reduces transposition only, repression evolves rapidly and adaptively after the genome is invaded by a new TE in simulated populations. We further show that the spread of repressor alleles through simulated populations is greatly enhanced by two additional TE-imposed fitness costs: dysgenic sterility and ectopic recombination. Finally, we demonstrate that the adaptive mutation rate to repression is a critical parameter that influences both the evolutionary trajectory of host repression and the associated proliferation of TEs after invasion in simulated populations. Our findings suggest that adaptive evolution of TE regulation may be stronger and more prevalent than previously appreciated, and provide a framework for interpreting empirical data.}, } @article {pmid30251433, year = {2018}, author = {Sánchez-Hernández, J and Nunn, AD and Adams, CE and Amundsen, PA}, title = {Causes and consequences of ontogenetic dietary shifts: a global synthesis using fish models.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12468}, pmid = {30251433}, issn = {1469-185X}, support = {I2C//Consellería de Cultura, Educación e Ordenación Universitaria, Xunta de Galicia/ ; }, abstract = {Ontogenetic dietary shifts (ODSs), the changes in diet utilisation occurring over the life span of an individual consumer, are widespread in the animal kingdom. Understanding ODSs provides fundamental insights into the biological and ecological processes that function at the individual, population and community levels, and is critical for the development and testing of hypotheses around key concepts in trophic theory on model organisms. Here, we synthesise historic and contemporary research on ODSs in fishes, and identify where further research is required. Numerous biotic and abiotic factors can directly or indirectly influence ODSs, but the most influential of these may vary spatially, temporally and interspecifically. Within the constraints imposed by prey availability, we identified competition and predation risk as the major drivers of ODSs in fishes. These drivers do not directly affect the trophic ontogeny of fishes, but may have an indirect effect on diet trajectories through ontogenetic changes in habitat use and concomitant changes in prey availability. The synthesis provides compelling evidence that ODSs can have profound ecological consequences for fish by, for example, enhancing individual growth and lifetime reproductive output or reducing the risk of mortality. ODSs may also influence food-web dynamics and facilitate the coexistence of sympatric species through resource partitioning, but we currently lack a holistic understanding of the consequences of ODSs for population, community and ecosystem processes and functioning. Studies attempting to address these knowledge gaps have largely focused on theoretical approaches, but empirical research under natural conditions, including phylogenetic and evolutionary considerations, is required to test the concepts. Research focusing on inter-individual variation in ontogenetic trajectories has also been limited, with the complex relationships between individual behaviour and environmental heterogeneity representing a particularly promising area for future research.}, } @article {pmid30251365, year = {2018}, author = {Yoon, SJ and Park, YJ and Kim, JS and Lee, S and Lee, SH and Choi, S and Min, JK and Choi, I and Ryu, CM}, title = {Pseudomonas syringae evades phagocytosis by animal cells via type III effector-mediated regulation of actin filament plasticity.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3980-3991}, doi = {10.1111/1462-2920.14426}, pmid = {30251365}, issn = {1462-2920}, support = {NRF-2015M3A9E6028953//National Research Foundation of Korea/ ; PJ002015//Rural Development Administration/ ; }, abstract = {Certain animal and plant pathogenic bacteria have developed virulence factors including effector proteins that enable them to overcome host immunity. A plant pathogen, Pseudomonas syringae pv. tomato (Pto) secretes a large repertoire of effectors via a type III secretory apparatus, thereby suppressing plant immunity. Here, we show that Pto causes sepsis in mice. Surprisingly, the effector HopQ1 disrupted animal phagocytosis by inhibiting actin rearrangement via direct interaction with the LIM domain of the animal target protein LIM kinase, a key regulator of actin polymerization. The results provide novel insight into animal host-plant pathogen interactions. In addition, the current study firstly demonstrates that certain plant pathogenic bacteria such as Pto evade phagocytosis by animal cells due to cross-kingdom suppression of host immunity.}, } @article {pmid30251329, year = {2018}, author = {Buisson, E and Le Stradic, S and Silveira, FAO and Durigan, G and Overbeck, GE and Fidelis, A and Fernandes, GW and Bond, WJ and Hermann, JM and Mahy, G and Alvarado, ST and Zaloumis, NP and Veldman, JW}, title = {Resilience and restoration of tropical and subtropical grasslands, savannas, and grassy woodlands.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12470}, pmid = {30251329}, issn = {1469-185X}, support = {//French Embassy / UFMG Chairs 2015/ ; //CNRS PICS 2018-2020 [RESIGRASS]/ ; //Programme de mobilité entrante UAPV (Avignon Univ)/ ; 306170/2015-9, 310022/2015-0, 312292/2016-3, 477618/2013-8//CNPq (Conselho Nacional de Desenvolvimento Científico e Tecnológico)/ ; //FAPEMIG/ ; #2015/06743-0, #2014/12337-2, #2014/12728-1, #2016/13232-5, #2017/14236-7, #2018/03755-6//FAPESP (Fundação de Amparo à Pesquisa do Estado de São Paulo)/ ; 0950_20122//Fundação Boticário/ ; }, abstract = {Despite growing recognition of the conservation values of grassy biomes, our understanding of how to maintain and restore biodiverse tropical grasslands (including savannas and open-canopy grassy woodlands) remains limited. To incorporate grasslands into large-scale restoration efforts, we synthesised existing ecological knowledge of tropical grassland resilience and approaches to plant community restoration. Tropical grassland plant communities are resilient to, and often dependent on, the endogenous disturbances with which they evolved - frequent fires and native megafaunal herbivory. In stark contrast, tropical grasslands are extremely vulnerable to human-caused exogenous disturbances, particularly those that alter soils and destroy belowground biomass (e.g. tillage agriculture, surface mining); tropical grassland restoration after severe soil disturbances is expensive and rarely achieves management targets. Where grasslands have been degraded by altered disturbance regimes (e.g. fire exclusion), exotic plant invasions, or afforestation, restoration efforts can recreate vegetation structure (i.e. historical tree density and herbaceous ground cover), but species-diverse plant communities, including endemic species, are slow to recover. Complicating plant-community restoration efforts, many tropical grassland species, particularly those that invest in underground storage organs, are difficult to propagate and re-establish. To guide restoration decisions, we draw on the old-growth grassland concept, the novel ecosystem concept, and theory regarding tree cover along resource gradients in savannas to propose a conceptual framework that classifies tropical grasslands into three broad ecosystem states. These states are: (1) old-growth grasslands (i.e. ancient, biodiverse grassy ecosystems), where management should focus on the maintenance of disturbance regimes; (2) hybrid grasslands, where restoration should emphasise a return towards the old-growth state; and (3) novel ecosystems, where the magnitude of environmental change (i.e. a shift to an alternative ecosystem state) or the socioecological context preclude a return to historical conditions.}, } @article {pmid30251319, year = {2018}, author = {Martin, RM and Moniruzzaman, M and Mucci, NC and Willis, A and Woodhouse, JN and Xian, Y and Xiao, C and Brussaard, CPD and Wilhelm, SW}, title = {Cylindrospermopsis raciborskii Virus and host: genomic characterization and ecological relevance.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14425}, pmid = {30251319}, issn = {1462-2920}, support = {//Kenneth & Blaire Mossman Endowment/ ; //NIOZ/ ; LP130100311//ARC-Linkage/ ; //University of Tennessee/ ; DEB 1240870//National Science Foundation/ ; IOS 141528//National Science Foundation/ ; }, abstract = {Cylindrospermopsis (Raphidiopsis) raciborskii is an invasive, filamentous, nitrogen-fixing cyanobacterium that forms frequent blooms in freshwater habitats. While viruses play key roles in regulating the abundance, production and diversity of their hosts in aquatic ecosystems, the role(s) of viruses in the ecology of C. raciborskii is almost unexplored. Progress in this field has been hindered by the absence of a characterized virus-host system in C. raciborskii. To bridge this gap, we sequenced the genome of CrV-01T, a previously isolated cyanosiphovirus, and its host, C. raciborskii strain Cr2010. Analyses suggest that CrV-01T represents a distinct clade of siphoviruses infecting, and perhaps lysogenizing, filamentous cyanobacteria. Its genome contains unique features that include an intact CRISPR array and a 12 kb inverted duplication. Evidence suggests CrV-01T recently gained the ability to infect Cr2010 and recently lost the ability to form lysogens. The cyanobacterial host contains a CRISPR-Cas system with CRISPR spacers matching protospacers within the inverted duplication of the CrV-01T genome. Examination of metagenomes demonstrates that viruses with high genetic identity to CrV-01T, but lacking the inverted duplication, are present in C. raciborskii blooms in Australia. The unique genomic features of the CrV/Cr2010 system offers opportunities to investigate in more detail virus-host interactions in an ecologically important bloom-forming cyanobacterium.}, } @article {pmid30250738, year = {2018}, author = {Nunn, CL}, title = {The 1918 influenza pandemic: Ecological, historical, and evolutionary perspectives.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {199-200}, doi = {10.1093/emph/eoy021}, pmid = {30250738}, issn = {2050-6201}, } @article {pmid30250729, year = {2018}, author = {Aguilera, MA and Dobringer, J and Petit, IJ}, title = {Heterogeneity of ecological patterns, processes, and funding of marine manipulative field experiments conducted in Southeastern Pacific coastal ecosystems.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8627-8638}, pmid = {30250729}, issn = {2045-7758}, abstract = {Ecological manipulative experiments conducted in marine coastal ecosystems have substantially improved ecological theory during the last decades and have provided useful knowledge for the management and conservation of coastal ecosystems. Although different studies report global trends in ecological patterns worldwide, Southeastern Pacific coastal ecosystems have been poorly considered. Given that the SE Pacific coast encompasses diverse coastal ecosystems, consideration of studies conducted along this range can shed light on the heterogeneity of processes regulating coastal communities. We reviewed the biotic interactions and habitat type considered, as well as the complexity in terms of spatial and temporal extent of manipulative field experimental studies conducted along the SE Pacific coast from 0°S to 56°S (Ecuador to Chile). We test the effect of funding reported by different studies as a main factor limiting experimental complexity. From field ecological studies published from 1970 to 2016, we found that 81 studies were truly manipulative, in which one or multiple factors were "manipulated." Around 77% of these studies were located between 21°S and 40°S, and conducted in intertidal rocky habitats. An increase in experimental studies was observed between 2010 and 2015, especially focused on herbivore-alga interactions, although we found that both the temporal extent and spatial extent of these studies have shown a decrease in recent decades. Funding grant amount reported had a positive effect on elapsed time of field experiments, but no effect was observed on spatial extent or in the biotic interactions considered. Elapsed time of experiments was different among the main biotic interactions considered, that is, herbivory, predation, and competition. We suggest that to further progress in applied ecological knowledge, it will be necessary to consider pollution and urbanization processes explicitly using a field experimental framework. This information could improve our understanding of how ecosystems present along the SE Pacific coast respond to climate change and increased levels of human interventions.}, } @article {pmid30250728, year = {2018}, author = {Gutzat, F and Dormann, CF}, title = {Decaying trees improve nesting opportunities for cavity-nesting birds in temperate and boreal forests: A meta-analysis and implications for retention forestry.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8616-8626}, pmid = {30250728}, issn = {2045-7758}, abstract = {Many studies have dealt with the habitat requirements of cavity-nesting birds, but there is no meta-analysis on the subject and individual study results remain vague or contradictory. We conducted a meta-analysis to increase the available evidence for nest-site selection of cavity-nesting birds. Literature was searched in Web of Science and Google Scholar and included studies that provide data on the habitat requirements of cavity-nesting birds in temperate and boreal forests of varying naturalness. To compare nest and non-nest-tree characteristics, the following data were collected from the literature: diameter at breast height (DBH) and its standard deviation (SD), sample size of trees with and without active nest, amount of nest and available trees described as dead or with a broken crown, and amount of nest and available trees that were lacking these characteristics. Further collected data included bird species nesting in the cavities and nest-building type (nonexcavator/excavator), forest type (coniferous/deciduous/mixed), biome (temperate/boreal), and naturalness (managed/natural). From these data, three effect sizes were calculated that describe potential nest trees in terms of DBH, vital status (dead/alive), and crown status (broken/intact). These tree characteristics can be easily recognized by foresters. The results show that on average large-diameter trees, dead trees, and trees with broken crowns were selected for nesting. The magnitude of this effect varied depending primarily on bird species and the explanatory variables forest type and naturalness. Biome had lowest influence (indicated by ΔAIC). We conclude that diameter at breast height, vitality, and crown status can be used as tree characteristics for the selection of trees that should be retained in selectively harvested forests.}, } @article {pmid30250727, year = {2018}, author = {Kobayashi, S and Denda, T and Liao, CC and Lin, YH and Wu, SH and Izawa, M}, title = {Floral traits of mammal-pollinated Mucuna macrocarpa (Fabaceae): Implications for generalist-like pollination systems.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8607-8615}, pmid = {30250727}, issn = {2045-7758}, abstract = {Floral traits are adapted by plants to attract pollinators. Some of those plants that have different pollinators in different regions adapt to each pollinator in each region to maximize their pollination success. Mucuna macrocarpa (Fabaceae) limits the pollinators using its floral structure and is pollinated by different mammals in different regions. Here, we examine the relationships between floral traits of M. macrocarpa and the external morphology of mammalian pollinators in different regions of its distribution. Field surveys were conducted on Kyushu and Okinawajima Island in Japan, and in Taiwan, where the main pollinators are the Japanese macaque Macaca fuscata, Ryukyu flying fox Pteropus dasymallus, and red-bellied squirrel Callosciurus erythraeus, respectively. We measured the floral shapes, nectar secretion patterns, sugar components, and external morphology of the pollinators. Results showed that floral shape was slightly different among regions and that flower sizes were not correlated with the external morphology of the pollinators. Volume and sugar rate of nectar were not significantly different among the three regions and did not change throughout the day in any of the regions. However, nectar concentration was higher in Kyushu than in the other two regions. These results suggest that the floral traits of M. macrocarpa are not adapted to each pollinator in each region. Although this plant limits the number of pollinators using its flower structure, it has not adapted to specific mammals and may attract several species of mammals. Such generalist-like pollination system might have evolved in the Old World.}, } @article {pmid30250726, year = {2018}, author = {Manzanedo, RD and Ballesteros-Cánovas, J and Schenk, F and Stoffel, M and Fischer, M and Allan, E}, title = {Increase in CO2 concentration could alter the response of Hedera helix to climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8598-8606}, pmid = {30250726}, issn = {2045-7758}, abstract = {Increasing CO 2 concentration ([CO 2]) is likely to affect future species distributions, in interaction with other climate change drivers. However, current modeling approaches still seldom consider interactions between climatic factors and the importance of these interactions therefore remains mostly unexplored. Here, we combined dendrochronological and modeling approaches to study the interactive effects of increasing [CO 2] and temperature on the distribution of one of the main European liana species, Hedera helix. We combined a classical continent-wide species distribution modeling approach with a case study using H. helix and Quercus cerris tree rings, where we explored the long-term influence of a variety of climate drivers, including increasing [CO 2], and their interactions, on secondary growth. Finally, we explored how our findings could influence the model predictions. Climate-only model predictions showed a small decrease in habitat suitability for H. helix in Europe; however, this was accompanied by a strong shift in the distribution toward the north and east. Our growth ring data suggested that H. helix can benefit from high [CO 2] under warm conditions, more than its tree hosts, which showed a weaker response to [CO 2] coupled with higher cavitation risk under high temperature. Increasing [CO 2] might therefore offset the negative effects of high temperatures on H. helix, and we illustrate how this might translate into maintenance of H. helix in warmer areas. Our results highlight the need to consider carbon fertilization and interactions between climate variables in ecological modeling. Combining dendrochronological analyses with spatial distribution modeling may provide opportunities to refine predictions of how climate change will affect species distributions.}, } @article {pmid30250725, year = {2018}, author = {Amissah, L and Mohren, GMJ and Kyereh, B and Agyeman, VK and Poorter, L}, title = {Rainfall seasonality and drought performance shape the distribution of tropical tree species in Ghana.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8582-8597}, pmid = {30250725}, issn = {2045-7758}, abstract = {Tree species distribution in lowland tropical forests is strongly associated with rainfall amount and distribution. Not only plant water availability, but also irradiance, soil fertility, and pest pressure covary along rainfall gradients. To assess the role of water availability in shaping species distribution, we carried out a reciprocal transplanting experiment in gaps in a dry and a wet forest site in Ghana, using 2,670 seedlings of 23 tree species belonging to three contrasting rainfall distributions groups (dry species, ubiquitous species, and wet species). We evaluated seasonal patterns in climatic conditions, seedling physiology and performance (survival and growth) over a 2-year period and related seedling performance to species distribution along Ghana's rainfall gradient. The dry forest site had, compared to the wet forest, higher irradiance, and soil nutrient availability and experienced stronger atmospheric drought (2.0 vs. 0.6 kPa vapor pressure deficit) and reduced soil water potential (-5.0 vs. -0.6 MPa soil water potential) during the dry season. In both forests, dry species showed significantly higher stomatal conductance and lower leaf water potential, than wet species, and in the dry forest, dry species also realized higher drought survival and growth rate than wet species. Dry species are therefore more drought tolerant, and unlike the wet forest species, they achieve a home advantage. Species drought performance in the dry forest relative to the wet forest significantly predicted species position on the rainfall gradient in Ghana, indicating that the ability to grow and survive better in dry forests and during dry seasons may allow species to occur in low rainfall areas. Drought is therefore an important environmental filter that influences forest composition and dynamics. Currently, many tropical forests experience increase in frequency and intensity of droughts, and our results suggest that this may lead to reduction in tree productivity and shifts in species distribution.}, } @article {pmid30250724, year = {2018}, author = {Guyonnet, JP and Cantarel, AAM and Simon, L and Haichar, FEZ}, title = {Root exudation rate as functional trait involved in plant nutrient-use strategy classification.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8573-8581}, pmid = {30250724}, issn = {2045-7758}, abstract = {Plants adopt a variety of life history strategies to succeed in the Earth's diverse environments. Using functional traits which are defined as "morphological, biochemical, physiological, or phonological" characteristics measurable at the individual level, plants are classified according to their species' adaptative strategies, more than their taxonomy, from fast growing plant species to slower-growing conservative species. These different strategies probably influence the input and output of carbon (C)-resources, from the assimilation of carbon by photosynthesis to its release in the rhizosphere soil via root exudation. However, while root exudation was known to mediate plant-microbe interactions in the rhizosphere, it was not used as functional trait until recently. Here, we assess whether root exudate levels are useful plant functional traits in the classification of plant nutrient-use strategies and classical trait syndromes? For this purpose, we conducted an experiment with six grass species representing along a gradient of plant resource-use strategies, from conservative species, characterized by low biomass nitrogen (N) concentrations and a long lifespans, to exploitative species, characterized by high rates of photosynthesis and rapid rates of N acquisition. Leaf and root traits were measured for each grass and root exudate rate for each planted soil sample. Classical trait syndromes in plant ecology were found for leaf and root traits, with negative relationships observed between specific leaf area and leaf dry matter content or between specific root length and root dry matter content. However, a new root trait syndrome was also found with root exudation levels correlating with plant resource-use strategy patterns, specifically, between root exudation rate and root dry matter content. We therefore propose root exudation rate can be used as a key functional trait in plant ecology studies and plant strategy classification.}, } @article {pmid30250723, year = {2018}, author = {Olson, LE and Squires, JR and Roberts, EK and Ivan, JS and Hebblewhite, M}, title = {Sharing the same slope: Behavioral responses of a threatened mesocarnivore to motorized and nonmotorized winter recreation.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8555-8572}, pmid = {30250723}, issn = {2045-7758}, abstract = {Winter recreation is a widely popular activity and is expected to increase due to changes in recreation technology and human population growth. Wildlife are frequently negatively impacted by winter recreation, however, through displacement from habitat, alteration of activity patterns, or changes in movement behavior. We studied impacts of dispersed and developed winter recreation on Canada lynx (Lynx canadensis) at their southwestern range periphery in Colorado, USA. We used GPS collars to track movements of 18 adult lynx over 4 years, coupled with GPS devices that logged 2,839 unique recreation tracks to provide a detailed spatial estimate of recreation intensity. We assessed changes in lynx spatial and temporal patterns in response to motorized and nonmotorized recreation, as well as differences in movement rate and path tortuosity. We found that lynx decreased their movement rate in areas with high-intensity back-country skiing and snowmobiling, and adjusted their temporal patterns so that they were more active at night in areas with high-intensity recreation. We did not find consistent evidence of spatial avoidance of recreation: lynx exhibited some avoidance of areas with motorized recreation, but selected areas in close proximity to nonmotorized recreation trails. Lynx appeared to avoid high-intensity developed ski resorts, however, especially when recreation was most intense. We conclude that lynx in our study areas did not exhibit strong negative responses to dispersed recreation, but instead altered their behavior and temporal patterns in a nuanced response to recreation, perhaps to decrease direct interactions with recreationists. However, based on observed avoidance of developed recreation, there may be a threshold of human disturbance above which lynx cannot coexist with winter recreation.}, } @article {pmid30250722, year = {2018}, author = {Lin, X and Hu, S and Liu, S and Huang, H}, title = {Unexpected prey of juvenile spotted scat (Scatophagus argus) near a wharf: The prevalence of fouling organisms in stomach contents.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8547-8554}, pmid = {30250722}, issn = {2045-7758}, abstract = {A knowledge of fish diets can contribute to revealing the trophic role and ecological function of species in aquatic ecosystems. At present, however, there are no efficient or comprehensive methods for analyzing fish diets. In this study, we investigated the diets of juvenile Scatophagus argus collected near a wharf in Daya Bay, China, by dissection and high-throughput sequencing (HTS) using the 18S rDNA V4 region. Microscopy disclosed large amounts of bryozoans and unrecognizable detritus. In contrast, HTS analysis indicated that the fish diets were considerably more diverse than visual inspection suggested. After eliminating fish sequences, approximately 17,000 sequences from taxa in nine phyla (Ciliophora, Bryozoa, Annelida, Bacillariophyta, Chlorophyta, Arthropoda, Dinoflagellata, Tunicata, and Phaeophyta) were identified from the analysis of stomach contents. Twenty-one food categories were identified, most of which (95.2%) were benthic fouling organisms that could easily be collected around wharfs. These consisted of bryozoans (31.9%), ciliates (45.7%), polychaetes (14.6%), and green algae (3.0%). Therefore, to adapt to anthropogenic habitat modification, the fish had probably shifted from planktonic to benthic feeding. The prevalence of fouling organisms in the stomachs of juvenile S. argus indicates that the fish have responded to habitat changes by widening their food spectrum. This adaptation may have increased their chances of survival. The fouling organisms that inhabit highly perturbed coastal ecosystems could represent a food source for animals at higher trophic levels. Our results accordingly suggest that human activity might significantly influence fish feeding behavior and material transfer along the food chain.}, } @article {pmid30250721, year = {2018}, author = {Pagano, G and Johnson, C and Hahn, DC and Arsenault, RJ}, title = {A new tool for studying waterfowl immune and metabolic responses: Molecular level analysis using kinome profiling.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8537-8546}, pmid = {30250721}, issn = {2045-7758}, abstract = {Here, we describe the design of an Anas-specific kinome peptide array that can be used to study the immunometabolic responses of mallard and American black duck to pathogens, contaminants, and environmental stress. The peptide arrays contain 2,642 unique phosphorylate-able peptide sequences representing 1,900 proteins. These proteins cover a wide array of metabolic and immunological processes, and 758 Gene Ontology Biological processes are statistically significantly represented on the duck peptide array of those 164 contain the term "metabolic" and 25 "immune." In addition, we conducted a comparison of mallard to American black duck at a genetic and proteomic level. Our results show a significant genomic and proteomic overlap between these two duck species, so that we have designed a cross-reactive peptide array capable of studying both species. This is the first reported development of a wildlife species-specific kinome peptide array.}, } @article {pmid30250720, year = {2018}, author = {Yang, Y and Morden, CW and Sporck-Koehler, MJ and Sack, L and Wagner, WL and Berry, PE}, title = {Repeated range expansion and niche shift in a volcanic hotspot archipelago: Radiation of C4 Hawaiian Euphorbia subgenus Chamaesyce (Euphorbiaceae).}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8523-8536}, pmid = {30250720}, issn = {2045-7758}, abstract = {Woody perennial plants on islands have repeatedly evolved from herbaceous mainland ancestors. Although the majority of species in Euphorbia subgenus Chamaesyce section Anisophyllum (Euphorbiaceae) are small and herbaceous, a clade of 16 woody species diversified on the Hawaiian Islands. They are found in a broad range of habitats, including the only known C4 plants adapted to wet forest understories. We investigate the history of island colonization and habitat shift in this group. We sampled 153 individuals in 15 of the 16 native species of Hawaiian Euphorbia on six major Hawaiian Islands, plus 11 New World close relatives, to elucidate the biogeographic movement of this lineage within the Hawaiian island chain. We used a concatenated chloroplast DNA data set of more than eight kilobases in aligned length and applied maximum likelihood and Bayesian inference for phylogenetic reconstruction. Age and phylogeographic patterns were co-estimated using BEAST. In addition, we used nuclear ribosomal ITS and the low-copy genes LEAFY and G3pdhC to investigate the reticulate relationships within this radiation. Hawaiian Euphorbia first arrived on Kaua`i or Ni`ihau ca. 5 million years ago and subsequently diverged into 16 named species with extensive reticulation. During this process Hawaiian Euphorbia dispersed from older to younger islands through open vegetation that is disturbance-prone. Species that occur under closed vegetation evolved in situ from open vegetation of the same island and are only found on the two oldest islands of Kaua`i and O`ahu. The biogeographic history of Hawaiian Euphorbia supports a progression rule with within-island shifts from open to closed vegetation.}, } @article {pmid30250719, year = {2018}, author = {Pease, JE and Grabowski, TB and Pease, AA and Bean, PT}, title = {Changing environmental gradients over forty years alter ecomorphological variation in Guadalupe Bass Micropterus treculii throughout a river basin.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8508-8522}, pmid = {30250719}, issn = {2045-7758}, abstract = {Understanding the degree of intraspecific variation within and among populations is a key aspect of predicting the capacity of a species to respond to anthropogenic disturbances. However, intraspecific variation is usually assessed at either limited temporal, but broad spatial scales or vice versa, which can make assessing changes in response to long-term disturbances challenging. We evaluated the relationship between the longitudinal gradient of changing flow regimes and land use/land cover patterns since 1980 and morphological variation of Guadalupe Bass Micropterus treculii throughout the Colorado River Basin of central Texas. The Colorado River Basin in Texas has experienced major alterations to the hydrologic regime due to changing land- and water-use patterns. Historical collections of Guadalupe Bass prior to rapid human-induced change present the unique opportunity to study the response of populations to varying environmental conditions through space and time. Morphological differentiation of Guadalupe Bass associated with temporal changes in flow regimes and land use/land cover patterns suggests that they are exhibiting intraspecific trait variability, with contemporary individuals showing increased body depth, in response to environmental alteration through time (specifically related to an increase in herbaceous land cover, maximum flows, and the number of low pulses and high pulses). Additionally, individuals from tributaries with increased hydrologic alteration associated with urbanization or agricultural withdrawals tended to have a greater distance between the anal and caudal fin. These results reveal trait variation that may help to buffer populations under conditions of increased urbanization and sprawl, human population growth, and climate risk, all of which impose novel selective pressures, especially on endemic species like Guadalupe Bass. Our results contribute an understanding of the adaptability and capacity of an endemic population to respond to expected future changes based on demographic or climatic projection.}, } @article {pmid30250718, year = {2018}, author = {Wilson, RE and Ely, CR and Talbot, SL}, title = {Flyway structure in the circumpolar greater white-fronted goose.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8490-8507}, pmid = {30250718}, issn = {2045-7758}, support = {P20 RR016466/RR/NCRR NIH HHS/United States ; }, abstract = {Dispersal and migratory behavior are influential factors in determining how genetic diversity is distributed across the landscape. In migratory species, genetic structure can be promoted via several mechanisms including fidelity to distinct migratory routes. Particularly within North America, waterfowl management units have been delineated according to distinct longitudinal migratory flyways supported by banding data and other direct evidence. The greater white-fronted goose (Anser albifrons) is a migratory waterfowl species with a largely circumpolar distribution consisting of up to six subspecies roughly corresponding to phenotypic variation. We examined the rangewide population genetic structure of greater white-fronted geese using mtDNA control region sequence data and microsatellite loci from 23 locales across North America and Eurasia. We found significant differentiation in mtDNA between sampling locales with flyway delineation explaining a significant portion of the observed genetic variation (~12%). This is concordant with band recovery data which shows little interflyway or intercontinental movements. However, microsatellite loci revealed little genetic structure suggesting a panmictic population across most of the Arctic. As with many high-latitude species, Beringia appears to have played a role in the diversification of this species. A common Beringian origin of North America and Asian populations and a recent divergence could at least partly explain the general lack of structure at nuclear markers. Further, our results do not provide strong support for the various taxonomic proposals for this species except for supporting the distinctness of two isolated breeding populations within Cook Inlet, Alaska (A. a. elgasi) and Greenland (A. a. flavirostris), consistent with their subspecies status.}, } @article {pmid30250717, year = {2018}, author = {Muvengwi, J and Chikorowondo, G and Mbiba, M and Gandiwa, E}, title = {Diversity and abundance of macro-invertebrates on abandoned cattle kraals in a semi-arid savanna.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8477-8489}, pmid = {30250717}, issn = {2045-7758}, abstract = {Abandoned cattle (Bos taurus) kraals are sources of habitat heterogeneity in dystrophic semi-arid African savannas with a strong positive effect on soil nutrients and plant productivity. However, little is known regarding how macro-invertebrate assemblages vary between abandoned kraals and the surrounding savanna matrix. We tested whether herbaceous biomass and basal and aerial covers and soil nutrients have an effect on aboveground and belowground macro-invertebrate assemblages. Twelve abandoned kraals were contrasted with their paired control plots for soil characteristics, herbaceous productivity, and macro-invertebrate assemblages in Save Valley Conservancy, Zimbabwe. Abandoned kraals had significantly higher concentrations of soil nitrogen (N), phosphorus (P), potassium (K), and calcium (Ca) as well as herbaceous biomass and basal and aerial covers than control plots. Both aboveground and belowground macro-invertebrate species richness were higher on abandoned kraals. However, only belowground macro-invertebrate diversity (Shannon H' and Hill number 1) was significantly higher on abandoned kraals. Soil nutrients and herbaceous productivity had positive and significant correlations with the dominant taxa (Coleoptera, Hymenoptera, Hemiptera, Isoptera, and Myriapoda) on abandoned kraals. These results add to the growing body of evidence that abandoned kraals exert significant effects on savanna spatial heterogeneity years later, with implications on ecosystem processes and functioning.}, } @article {pmid30250716, year = {2018}, author = {Varma, V and Catherin, AM and Sankaran, M}, title = {Effects of increased N and P availability on biomass allocation and root carbohydrate reserves differ between N-fixing and non-N-fixing savanna tree seedlings.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8467-8476}, pmid = {30250716}, issn = {2045-7758}, abstract = {In mixed tree-grass ecosystems, tree recruitment is limited by demographic bottlenecks to seedling establishment arising from inter- and intra-life-form competition, and disturbances such as fire. Enhanced nutrient availability resulting from anthropogenic nitrogen (N) and phosphorus (P) deposition can alter the nature of these bottlenecks by changing seedling growth and biomass allocation patterns, and lead to longer-term shifts in tree community composition if different plant functional groups respond differently to increased nutrient availability. However, the extent to which tree functional types characteristic of savannas differ in their responses to increased N and P availability remains unclear. We quantified differences in above- and belowground biomass, and root carbohydrate contents in seedlings of multiple N-fixing and non-N-fixing tree species characteristic of Indian savanna and dry forest ecosystems in response to experimental N and P additions. These parameters are known to influence the ability of plants to compete, as well as survive and recover from fires. N-fixers in our study were co-limited by N and P availability, while non-N-fixers were N limited. Although both functional groups increased biomass production following fertilization, non-N-fixers were more responsive and showed greater relative increases in biomass with fertilization than N-fixers. N-fixers had greater baseline investment in belowground resources and root carbohydrate stocks, and while fertilization reduced root:shoot ratios in both functional groups, root carbohydrate content only reduced with fertilization in non-N-fixers. Our results indicate that, even within a given system, plants belonging to different functional groups can be limited by, and respond differentially to, different nutrients, suggesting that long-term consequences of nutrient deposition are likely to vary across savannas contingent on the relative amounts of N and P being deposited in sites.}, } @article {pmid30250715, year = {2018}, author = {Ladwig, LM and Damschen, EI and Rogers, DA}, title = {Sixty years of community change in the prairie-savanna-forest mosaic of Wisconsin.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8458-8466}, pmid = {30250715}, issn = {2045-7758}, abstract = {Biodiversity loss is a global concern, and maintaining habitat complexity in naturally patchy landscapes can help retain regional diversity. A mosaic of prairie, savanna, and forest historically occurred across central North America but currently is highly fragmented due to human land conversion. It is unclear how each habitat type now contributes to regional diversity. Using legacy data, we resurveyed savanna plant communities originally surveyed in the 1950s to compare change in savannas to that in remnant forests and prairies. Savanna community structure and composition changed substantially over the past 60 years. Tree canopy density nearly doubled and many prairie and savanna specialist species were replaced by forest and non-native species. All three habitats gained and lost many species since the 1950s, resulting in large changes in community composition from local colonizations and extinctions. Across all three habitats, regional species extinctions matched that of regional colonization resulting in no net change in regional species richness. Synthesis-Despite considerable species turnover within savannas, many species remain within the broader prairie-savanna-forest mosaic. Both regional extinctions and colonizations were high over the past 60 years, and maintaining the presence of all three community types-prairie, savanna and forest-on the landscape is critical to maintaining regional biodiversity.}, } @article {pmid30250714, year = {2018}, author = {Thoré, ESJ and Steenaerts, L and Philippe, C and Grégoir, A and Brendonck, L and Pinceel, T}, title = {Individual behavioral variation reflects personality divergence in the upcoming model organism Nothobranchius furzeri.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8448-8457}, pmid = {30250714}, issn = {2045-7758}, abstract = {In the animal kingdom, behavioral variation among individuals has often been reported. However, stable among-individual differences along a behavioral continuum-reflective of personality variation-have only recently become a key target of research. While a vast body of descriptive literature exists on animal personality, hypothesis-driven quantitative studies are largely deficient. One of the main constraints to advance the field is the lack of suitable model organisms. Here, we explore whether N. furzeri could be a valuable model to bridge descriptive and hypothesis-driven research to further unravel the causes, function and evolution of animal personality. As a first step toward this end, we perform a common garden laboratory experiment to examine if behavioral variation in the turquoise killifish Nothobranchius furzeri reflects personality divergence. Furthermore, we explore if multiple behavioral traits are correlated. We deliver "proof of principle" of personality variation among N. furzeri individuals in multiple behavioral traits. Because of the vast body of available genomic and physiological information, the well-characterized ecological background and an exceptionally short life cycle, N. furzeri is an excellent model organism to further elucidate the causes and implications of behavioral variation in an eco-evolutionary context.}, } @article {pmid30250713, year = {2018}, author = {Chinn, SM and Monson, DH and Tinker, MT and Staedler, MM and Crocker, DE}, title = {Lactation and resource limitation affect stress responses, thyroid hormones, immune function, and antioxidant capacity of sea otters (Enhydra lutris).}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8433-8447}, pmid = {30250713}, issn = {2045-7758}, abstract = {Lactation is the most energetically demanding stage of reproduction in female mammals. Increased energetic allocation toward current reproduction may result in fitness costs, although the mechanisms underlying these trade-offs are not well understood. Trade-offs during lactation may include reduced energetic allocation to cellular maintenance, immune response, and survival and may be influenced by resource limitation. As the smallest marine mammal, sea otters (Enhydra lutris) have the highest mass-specific metabolic rate necessitating substantial energetic requirements for survival. To provide the increased energy needed for lactation, female sea otters significantly increase foraging effort, especially during late-lactation. Caloric insufficiency during lactation is reflected in the high numbers of maternal deaths due to End-Lactation Syndrome in the California subpopulation. We investigated the effects of lactation and resource limitation on maternal stress responses, metabolic regulation, immune function, and antioxidant capacity in two subspecies of wild sea otters (northern: E. l. nereis and southern: E. l. kenyoni) within the California, Washington, and Alaska subpopulations. Lactation and resource limitation were associated with reduced glucocorticoid responses to acute capture stress. Corticosterone release was lower in lactating otters. Cortisol release was lower under resource limitation and suppression during lactation was only evident under resource limitation. Lactation and resource limitation were associated with alterations in thyroid hormones. Immune responses and total antioxidant capacity were not reduced by lactation or resource limitation. Southern sea otters exhibited higher concentrations of antioxidants, immunoglobulins, and thyroid hormones than northern sea otters. These data provide evidence for allocation trade-offs during reproduction and in response to nutrient limitation but suggest self-maintenance of immune function and antioxidant defenses despite energetic constraints. Income-breeding strategists may be especially vulnerable to the consequences of stress and modulation of thyroid function when food resources are insufficient to support successful reproduction and may come at a cost to survival, and thereby influence population trends.}, } @article {pmid30250712, year = {2018}, author = {Weterings, MJA and Moonen, S and Prins, HHT and van Wieren, SE and van Langevelde, F}, title = {Food quality and quantity are more important in explaining foraging of an intermediate-sized mammalian herbivore than predation risk or competition.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8419-8432}, pmid = {30250712}, issn = {2045-7758}, abstract = {During times of high activity by predators and competitors, herbivores may be forced to forage in patches of low-quality food. However, the relative importance in determining where and what herbivores forage still remains unclear, especially for small- and intermediate-sized herbivores. Our objective was to test the relative importance of predator and competitor activity, and forage quality and quantity on the proportion of time spent in a vegetation type and the proportion of time spent foraging by the intermediate-sized herbivore European hare (Lepus europaeus). We studied red fox (Vulpes vulpes) as a predator species and European rabbit (Oryctolagus cuniculus) as a competitor. We investigated the time spent at a location and foraging time of hare using GPS with accelerometers. Forage quality and quantity were analyzed based on hand-plucked samples of a selection of the locally most important plant species in the diet of hare. Predator activity and competitor activity were investigated using a network of camera traps. Hares spent a higher proportion of time in vegetation types that contained a higher percentage of fibers (i.e., NDF). Besides, hares spent a higher proportion of time in vegetation types that contained relatively low food quantity and quality of forage (i.e., high percentage of fibers) during days that foxes (Vulpes vulpes) were more active. Also during days that rabbits (Oryctolagus cuniculus) were more active, hares spent a higher proportion of time foraging in vegetation types that contained a relatively low quality of forage. Although predation risk affected space use and foraging behavior, and competition affected foraging behavior, our study shows that food quality and quantity more strongly affected space use and foraging behavior than predation risk or competition. It seems that we need to reconsider the relative importance of the landscape of food in a world of fear and competition.}, } @article {pmid30250711, year = {2018}, author = {Haelewaters, D and Page, RA and Pfister, DH}, title = {Laboulbeniales hyperparasites (Fungi, Ascomycota) of bat flies: Independent origins and host associations.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8396-8418}, pmid = {30250711}, issn = {2045-7758}, abstract = {The aim of this study was to explore the diversity of ectoparasitic fungi (Ascomycota, Laboulbeniales) that use bat flies (Diptera, Hippoboscoidea) as hosts. Bat flies themselves live as ectoparasites on the fur and wing membranes of bats (Mammalia, Chiroptera); hence this is a tripartite parasite system. Here, we collected bats, bat flies, and Laboulbeniales, and conducted phylogenetic analyses of Laboulbeniales to contrast morphology with ribosomal sequence data. Parasitism of bat flies by Laboulbeniales arose at least three times independently, once in the Eastern Hemisphere (Arthrorhynchus) and twice in the Western Hemisphere (Gloeandromyces, Nycteromyces). We hypothesize that the genera Arthrorhynchus and Nycteromyces evolved independently from lineages of ectoparasites of true bugs (Hemiptera). We assessed phylogenetic diversity of the genus Gloeandromyces by considering the LSU rDNA region. Phenotypic plasticity and position-induced morphological adaptations go hand in hand. Different morphotypes belong to the same phylogenetic species. Two species, G. pageanus and G. streblae, show divergence by host utilization. In our assessment of coevolution, we only observe congruence between the Old World clades of bat flies and Laboulbeniales. The other associations are the result of the roosting ecology of the bat hosts. This study has considerably increased our knowledge about bats and their associated ectoparasites and shown the necessity of including molecular data in Laboulbeniales taxonomy.}, } @article {pmid30250710, year = {2018}, author = {Tsuchiya, M and Chikaraishi, Y and Nomaki, H and Sasaki, Y and Tame, A and Uematsu, K and Ohkouchi, N}, title = {Compound-specific isotope analysis of benthic foraminifer amino acids suggests microhabitat variability in rocky-shore environments.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8380-8395}, pmid = {30250710}, issn = {2045-7758}, abstract = {The abundance and biomass of benthic foraminifera are high in intertidal rocky-shore habitats. However, the availability of food to support their high biomass has been poorly studied in these habitats compared to those at seafloor covered by sediments. Previous field and laboratory observations have suggested that there is diversity in the food preferences and modes of life among rocky-shore benthic foraminifera. In this study, we used the stable nitrogen isotopic composition of amino acids to estimate the trophic position, trophic niche, and feeding strategy of individual foraminifera species. We also characterized the configuration and structure of the endobiotic microalgae in foraminifera using transmission electron microscopy, and we identified the origin of endobionts based on nucleotide sequences. Our results demonstrated a large variation in the trophic positions of different foraminifera from the same habitat, a reflection of endobiotic features and the different modes of life and food preferences of the foraminifera. Foraminifera did not rely solely on exogenous food sources. Some species effectively used organic matter derived from endobionts in the cell cytoplasm. The high biomass and species density of benthic foraminifera found in intertidal rocky-shore habitats are thus probably maintained by the use of multiple nitrogen resources and by microhabitat segregation among species as a consequence.}, } @article {pmid30250709, year = {2018}, author = {Marion, L and Bergerot, B}, title = {Northern range shift may be due to increased competition induced by protection of species rather than to climate change alone.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8364-8379}, pmid = {30250709}, issn = {2045-7758}, abstract = {Few long-term, large-scale studies have been conducted about the factors likely to explain changes in species abundance and distribution in winter. Range shifts are generally attributed to the climate change or land use. This study shows that other factors such as species protection and the ensuing increasing numbers of individuals and competition could be involved. It details the progressive conquest of France, the most important European wintering area for great cormorant, in three decades as its legal protection by the EU Birds Directive. It is based on 13 exhaustive national counts. Cormorants first occupied the farthest areas (Atlantic and Mediterranean lagoons, then larger rivers) from the main-core European breeding area, with only progressive occupancy of the northeastern part later. This strategy mainly resulted from competition for optimal available feeding areas. Suboptimal areas (smaller wetlands harboring smaller night roosts, colder northeastern French areas) and progressive fragmentation of large night roosts into smaller, better located ones minimized flight costs. The coldest areas were occupied last, once other areas were saturated. Their occupancy was favored locally by the global climate change, but it played a minor role in these strategies. Both factors induced only a small NNE shift of the weighted centroid range of the wintering population (2.6 km/year) which mainly resulted from competition (buffer effect). Only the 2009 cold wave decreased the total number of wintering cormorants at the national scale, once the population had probably reached the carrying capacity of the country, while the previous cold waves had a minor effect. Comparatively, there was a greater SSE range shift of the weighted centroid of the breeding population (4.66 km/year). Range shifts of other recently protected species have been attributed to the sole climate change in the literature, but competition due to the saturation of usual wintering or breeding areas should be considered too.}, } @article {pmid30250708, year = {2018}, author = {Milner, AM and Picken, JL and Klaar, MJ and Robertson, AL and Clitherow, LR and Eagle, L and Brown, LE}, title = {River ecosystem resilience to extreme flood events.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8354-8363}, pmid = {30250708}, issn = {2045-7758}, abstract = {Floods have a major influence in structuring river ecosystems. Considering projected increases in high-magnitude rainfall events with climate change, major flooding events are expected to increase in many regions of the world. However, there is uncertainty about the effect of different flooding regimes and the importance of flood timing in structuring riverine habitats and their associated biotic communities. In addition, our understanding of community response is hindered by a lack of long-term datasets to evaluate river ecosystem resilience to flooding. Here we show that in a river ecosystem studied for 30 years, a major winter flood reset the invertebrate community to a community similar to one that existed 15 years earlier. The community had not recovered to the preflood state when recurrent summer flooding 9 years later reset the ecosystem back to an even earlier community. Total macroinvertebrate density was reduced in the winter flood by an order of magnitude more than the summer flood. Meiofaunal invertebrates were more resilient to the flooding than macroinvertebrates, possibly due to their smaller body size facilitating greater access to in-stream refugia. Pacific pink salmon escapement was markedly affected by the winter flood when eggs were developing in redds, compared to summer flooding, which occurred before the majority of eggs were laid. Our findings inform a proposed conceptual model of three possible responses to flooding by the invertebrate community in terms of switching to different states and effects on resilience to future flooding events. In a changing climate, understanding these responses is important for river managers to mitigate the biological impacts of extreme flooding effects.}, } @article {pmid30250707, year = {2018}, author = {Magro, A and Ramon-Portugal, F and Facon, B and Ducamp, C and Hemptinne, JL}, title = {The evolution of chemical defenses along invasion routes: Harmonia axyridis Pallas (Coccinellidae: Coleoptera) as a case study.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8344-8353}, pmid = {30250707}, issn = {2045-7758}, abstract = {The evolution of increased competitive ability (EICA) hypothesis (Blossey & Nötzold, 1995) postulates that escaping from coevolved enemies increases invaders fitness by energy reallocation from defenses and immunity to growth and reproduction. In this context, we evaluated the evidence of evolutionary change in invasive populations of Harmonia axyridis Pallas (Coccinellidae: Coleoptera). We measured egg defenses-cocktail of hydrocarbons on the egg's surface flagging egg toxicity and the concentration of the main alkaloid harmonine-in individuals from three populations along the invasion route (Japan: native, United States: introduced more than 30 years ago, South Africa: introduced in the early 2000s) in a common garden experiment. Our results support the EICA hypothesis: We found changes along the invasion route in the profiles of the hydrocarbons coating the eggs' surface and a decrease in the concentration of harmonine in eggs from the most recent invasive South African population compared to the long established in the United States and the native Japanese ones.}, } @article {pmid30250706, year = {2018}, author = {van Rees, CB and Reed, JM and Wilson, RE and Underwood, JG and Sonsthagen, SA}, title = {Landscape genetics identifies streams and drainage infrastructure as dispersal corridors for an endangered wetland bird.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8328-8343}, pmid = {30250706}, issn = {2045-7758}, abstract = {Anthropogenic alterations to landscape structure and composition can have significant impacts on biodiversity, potentially leading to species extinctions. Population-level impacts of landscape change are mediated by animal behaviors, in particular dispersal behavior. Little is known about the dispersal habits of rails (Rallidae) due to their cryptic behavior and tendency to occupy densely vegetated habitats. The effects of landscape structure on the movement behavior of waterbirds in general are poorly studied due to their reputation for having high dispersal abilities. We used a landscape genetic approach to test hypotheses of landscape effects on dispersal behavior of the Hawaiian gallinule (Gallinula galeata sandvicensis), an endangered subspecies endemic to the Hawaiian Islands. We created a suite of alternative resistance surfaces representing biologically plausible a priori hypotheses of how gallinules might navigate the landscape matrix and ranked these surfaces by their ability to explain observed patterns in genetic distance among 12 populations on the island of O`ahu. We modeled effective distance among wetland locations on all surfaces using both cumulative least-cost-path and resistance-distance approaches and evaluated relative model performance using Mantel tests, a causal modeling approach, and the mixed-model maximum-likelihood population-effects framework. Across all genetic markers, simulation methods, and model comparison metrics, surfaces that treated linear water features like streams, ditches, and canals as corridors for gallinule movement outperformed all other models. This is the first landscape genetic study on the movement behavior of any waterbird species to our knowledge. Our results indicate that lotic water features, including drainage infrastructure previously thought to be of minimal habitat value, contribute to habitat connectivity in this listed subspecies.}, } @article {pmid30250705, year = {2018}, author = {Kess, T and Galindo, J and Boulding, EG}, title = {Genomic divergence between Spanish Littorina saxatilis ecotypes unravels limited admixture and extensive parallelism associated with population history.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8311-8327}, pmid = {30250705}, issn = {2045-7758}, abstract = {The rough periwinkle, Littorina saxatilis, is a model system for studying parallel ecological speciation in microparapatry. Phenotypically parallel wave-adapted and crab-adapted ecotypes that hybridize within the middle shore are replicated along the northwestern coast of Spain and have likely arisen from two separate glacial refugia. We tested whether greater geographic separation corresponding to reduced opportunity for contemporary or historical gene flow between parallel ecotypes resulted in less parallel genomic divergence. We sequenced double-digested restriction-associated DNA (ddRAD) libraries from individual snails from upper, mid, and low intertidal levels of three separate sites colonized from two separate refugia. Outlier analysis of 4256 SNP markers identified 34.4% sharing of divergent loci between two geographically close sites; however, these sites each shared only 9.9%-15.1% of their divergent loci with a third more-distant site. STRUCTURE analysis revealed that genotypes from only three of 166 phenotypically intermediate mid-shore individuals appeared to result from recent hybridization, suggesting that hybrids cannot be reliably identified using shell traits. Hierarchical AMOVA indicated that the primary source of genomic differentiation was geographic separation, but also revealed greater similarity of the same ecotype across the two geographically close sites than previously estimated with dominant markers. These results from a model system for ecological speciation suggest that genomic parallelism is affected by the opportunity for historical or contemporary gene flow between populations.}, } @article {pmid30250704, year = {2018}, author = {Al-Kindi, KM and Al-Wahaibi, AK and Kwan, P and Andrew, NR and Welch, M and Al-Oufi, M and Al-Hinai, Z}, title = {Predicting the potential geographical distribution of parasitic natural enemies of the Dubas bug (Ommatissus lybicus de Bergevin) using geographic information systems.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8297-8310}, pmid = {30250704}, issn = {2045-7758}, abstract = {The Dubas bug (Ommatissus lybicus de Bergevin) is a pest species whose entire life cycle occurs on date palms, Phoenix dactylifera L, causing serious damage and reducing date palm growth and yield. Pseudoligosita babylonica Viggiani, Aprostocetus nr. Beatus, and Bocchus hyalinus Olmi are very important parasitic natural enemies of Ommatissus lybicus in northern Oman. In this study, random farms were selected to (a) model the link between occurrences of the Pseudoligosita babylonica, Aprostocetus nr beatus, and Bocchus hyalinus (dependent variables) with environmental, climatological, and Dubas bug infestation levels (the independent variables), and (b) produce distribution and predictive maps of these natural enemies in northern Oman. The multiple R2 values showed the model explained 63%, 89%, and 94% of the presence of P. babylonica, A. nr beatus, and Bocchus hyalinus, respectively. However, the distribution of each species appears to be influenced by distinct and geographically associated climatological and environmental factors, as well as habitat characteristics. This study reveals that spatial analysis and modeling can be highly useful for studying the distribution, the presence or absence of Dubas bugs, and their natural enemies. It is anticipated to help contribute to the reduction in the extent and costs of aerial and ground insecticidal spraying needed in date palm plantations.}, } @article {pmid30250703, year = {2018}, author = {Black, C and Collen, B and Lunn, D and Filby, D and Winnard, S and Hart, T}, title = {Time-lapse cameras reveal latitude and season influence breeding phenology durations in penguins.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8286-8296}, pmid = {30250703}, issn = {2045-7758}, abstract = {Variation in the phenology of avian taxa has long been studied to understand how a species reacts to environmental changes over both space and time. Penguins (Sphenicidae) serve as an important example of how biotic and abiotic factors influence certain stages of seabird phenology because of their large ranges and the extreme, dynamic conditions present in their Southern Ocean habitats. Here, we examined the phenology of gentoo (Pygoscelis papua) and chinstrap penguins (Pygoscelis antarctica) at 17 sites across the Scotia arc, including the first documented monitoring of phenology on the South Sandwich Islands, to determine which breeding phases are intrinsic, or rather vary across a species range and between years. We used a novel method to measure seabird breeding phenology and egg and chick survival: time-lapse cameras. Contrary to the long-standing theory that these phases are consistent between colonies, we found that latitude and season had a predominant influence on the length of the nest establishment, incubation, and guard durations. We observe a trend toward longer incubation times occurring farther south, where ambient temperatures are colder, which may indicate that exposure to cold slows embryo growth. Across species, in colonies located farther south, parents abandoned nests later when eggs were lost or chicks died and the latest record of eggs or chicks in the nest occurred earlier during the breeding period. The variation in both space and time observed in penguin phenology provides evidence that the duration of phases within the annual cycle of birds is not fundamental, or genetic, as previously understood. Additionally, the recorded phenology dates should inform field researchers on the best timing to count colonies at the peak of breeding, which is poorly understood.}, } @article {pmid30250702, year = {2018}, author = {Kesner, D and Kumschick, S}, title = {Gastropods alien to South Africa cause severe environmental harm in their global alien ranges across habitats.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8273-8285}, pmid = {30250702}, issn = {2045-7758}, abstract = {Alien gastropods have caused extensive harm to biodiversity and socioeconomic systems like agriculture and horticulture worldwide. For conservation and management purposes, information on impacts needs to be easily interpretable and comparable, and the factors that determine impacts understood. This study aimed to assess gastropods alien to South Africa to compare impact severity between species and understand how they vary between habitats and mechanisms. Furthermore, we explore the relationship between environmental and socioeconomic impacts, and both impact measures with life-history traits. We used the Environmental Impact Classification for Alien Taxa (EICAT) and Socio-Economic Impact Classification for Alien Taxa (SEICAT) to assess impacts of 34 gastropods alien to South Africa including evidence of impact from their entire alien range. We tested for correlations between environmental and socioeconomic impacts per species, and with fecundity and native latitude range using Kendall's tau tests. Kruskal-Wallis tests were used to compare impact magnitude among mechanisms and habitats, respectively. This study presents the first application of EICAT and SEICAT for invertebrates. There was no correlation between environmental impacts and socioeconomic impacts. Habitats did not differ regarding the severity of impacts recorded, but impacts via disease transmission were lower than other mechanisms. Neither fecundity nor native range latitude was correlated with impact magnitude. Despite gastropods being agricultural and horticultural pests globally, resilience of socioeconomic systems makes high impacts uncommon. Environmental systems may be vulnerable to gastropod impacts across habitats, having experienced multiple local extinctions of wetland island snail fauna. South Africa stands out as the only continental country that follows this trend. The knowledge gained on severity and nature of gastropod impacts is useful in risk assessment, which can aid conservation management. To make impact assessments more realistic, we suggest alternative ways of reporting impacts classified under EICAT and SEICAT.}, } @article {pmid30250701, year = {2018}, author = {Wang, H and Zheng, P and Aoki, D and Miyake, T and Yagami, S and Matsushita, Y and Fukushima, K and Nakagawa, M}, title = {Sexual and temporal variations in floral scent in the subdioecious shrub Eurya japonica Thunb.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8266-8272}, pmid = {30250701}, issn = {2045-7758}, abstract = {In many flowering plants, floral scents are a significant trait for visitors, playing an important role in attracting pollinators and/or detracting herbivores. The evolution of flowering plants from hermaphroditism to dioecy is often accompanied by sexual dimorphism in floral scent. In this study, floral scents emitted by different sexual morphs of the subdioecious shrub Eurya japonica Thunb. were collected using a dynamic headspace method, and sexual and temporal variations were evaluated by gas chromatography-mass spectrometry (GC-MS). Two volatiles, α-pinene and linalool, were identified as the major components of floral scents in females, hermaphrodites, and males. The males emit higher amounts of floral scents, particularly α-pinene, compared to females or hermaphrodites. Floral scents emitted by males generally decrease as flowers enter senescence, whereas those from females or hermaphrodites do not significantly differ. Intraspecific variations in floral scents of subdioecious species provided by this study would contribute to better understanding of sexual dimorphism in floral scent.}, } @article {pmid30250700, year = {2018}, author = {Ingram, T and Burns, ZD}, title = {Top-down control by an aquatic invertebrate predator increases with temperature but does not depend on individual behavioral type.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8256-8265}, pmid = {30250700}, issn = {2045-7758}, abstract = {Variation in behavioral traits among individuals within a population can have implications for food webs and ecosystems. Temperature change also alters food web structure and function, but potential interactions between warming and intraspecific behavioral variation are largely unexplored. We aimed to test how increased temperature, individual activity level of a predatory backswimmer (Anisops assimilis), and their interaction influenced the strength of top-down control of zooplankton and phytoplankton. We used stable isotopes to support our assumption that the study population of A. assimilis is zooplanktivorous, and behavioral trials to confirm that activity level is a repeatable trait. We established freshwater microcosms to test for effects of warming, backswimmer presence, and backswimmer behavioral type on zooplankton density, zooplankton composition, and phytoplankton chlorophyll a. Top-down control was present and was generally stronger at increased temperature. There was no indication that predator behavioral type influenced the strength of top-down control either on its own or interactively with temperature. Predator behavioral type may not be associated with ecologically important function in this species at the temporal and spatial scales addressed in this study, but the links between behavior, temperature, and food web processes are worthy of broader exploration.}, } @article {pmid30250699, year = {2018}, author = {Wagner, ND and Gramlich, S and Hörandl, E}, title = {RAD sequencing resolved phylogenetic relationships in European shrub willows (Salix L. subg. Chamaetia and subg. Vetrix) and revealed multiple evolution of dwarf shrubs.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8243-8255}, pmid = {30250699}, issn = {2045-7758}, abstract = {The large and diverse genus Salix L. is of particular interest for decades of biological research. However, despite the morphological plasticity, the reconstruction of phylogenetic relationships was so far hampered by the lack of informative molecular markers. Infrageneric classification based on morphology separates dwarf shrubs (subg. Chamaetia) and taller shrubs (subg. Vetrix), while previous phylogenetic studies placed species of these two subgenera just in one largely unresolved clade. Here we want to test the utility of genomic RAD sequencing markers for resolving relationships at different levels of divergence in Salix. Based on a sampling of 15 European species representing 13 sections of the two subgenera, we used five different RAD sequencing datasets generated by ipyrad to conduct phylogenetic analyses. Additionally we reconstructed the evolution of growth form and analyzed the genetic composition of the whole clade. The results showed fully resolved trees in both ML and BI analysis with high statistical support. The two subgenera Chamaetia and Vetrix were recognized as nonmonophyletic, which suggests that they should be merged. Within the Vetrix/Chamaetia clade, a division into three major subclades could be observed. All species were confirmed to be monophyletic. Based on our data, arctic-alpine dwarf shrubs evolved four times independently. The structure analysis showed five mainly uniform genetic clusters which are congruent in sister relationships observed in the phylogenies. Our study confirmed RAD sequencing as a useful genomic tool for the reconstruction of relationships on different taxonomic levels in the genus Salix.}, } @article {pmid30250698, year = {2018}, author = {Pillay, R and Hua, F and Loiselle, BA and Bernard, H and Fletcher, RJ}, title = {Multiple stages of tree seedling recruitment are altered in tropical forests degraded by selective logging.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8231-8242}, pmid = {30250698}, issn = {2045-7758}, abstract = {Tropical forest degradation is a global environmental issue. In degraded forests, seedling recruitment of canopy trees is vital for forest regeneration and recovery. We investigated how selective logging, a pervasive driver of tropical forest degradation, impacts canopy tree seedling recruitment, focusing on an endemic dipterocarp Dryobalanops lanceolata in Sabah, Borneo. During a mast-fruiting event in intensively logged and nearby unlogged forest, we examined four stages of the seedling recruitment process: seed production, seed predation, and negative density-dependent germination and seedling survival. Our results suggest that each stage of the seedling recruitment process is altered in logged forest. The seed crop of D. lanceolata trees in logged forest was one-third smaller than that produced by trees in unlogged forest. The functional role of vertebrates in seed predation increased in logged forest while that of non-vertebrates declined. Seeds in logged forest were less likely to germinate than those in unlogged forest. Germination increased with local-scale conspecific seed density in unlogged forest, but seedling survival tended to decline. However, both germination and seedling survival increased with local-scale conspecific seed density in logged forest. Notably, seed crop size, germination, and seedling survival tended to increase for larger trees in both unlogged and logged forests, suggesting that sustainable timber extraction and silvicultural practices designed to minimize damage to the residual stand are important to prevent seedling recruitment failure. Overall, these impacts sustained by several aspects of seedling recruitment in a mast-fruiting year suggest that intensive selective logging may affect long-term population dynamics of D. lanceolata. It is necessary to establish if other dipterocarp species, many of which are threatened by the timber trade, are similarly affected in tropical forests degraded by intensive selective logging.}, } @article {pmid30250697, year = {2018}, author = {Banerjee, S and Thrall, PH and Bissett, A and van der Heijden, MGA and Richardson, AE}, title = {Linking microbial co-occurrences to soil ecological processes across a woodland-grassland ecotone.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8217-8230}, pmid = {30250697}, issn = {2045-7758}, abstract = {Ecotones between distinct ecosystems have been the focus of many studies as they offer valuable insights into key drivers of community structure and ecological processes that underpin function. While previous studies have examined a wide range of above-ground parameters in ecotones, soil microbial communities have received little attention. Here we investigated spatial patterns, composition, and co-occurrences of archaea, bacteria, and fungi, and their relationships with soil ecological processes across a woodland-grassland ecotone. Geostatistical kriging and network analysis revealed that the community structure and spatial patterns of soil microbiota varied considerably between three habitat components across the ecotone. Woodland samples had significantly higher diversity of archaea while the grassland samples had significantly higher diversity of bacteria. Microbial co-occurrences reflected differences in soil properties and ecological processes. While microbial networks were dominated by bacterial nodes, different ecological processes were linked to specific microbial guilds. For example, soil phosphorus and phosphatase activity formed the largest clusters in their respective networks, and two lignolytic enzymes formed joined clusters. Bacterial ammonia oxidizers were dominant over archaeal oxidizers and showed a significant association (p < 0.001) with potential nitrification (PNR), with the PNR subnetwork being dominated by Betaproteobacteria. The top ten keystone taxa comprised six bacterial and four fungal OTUs, with Random Forest Analysis revealing soil carbon and nitrogen as the determinants of the abundance of keystone taxa. Our results highlight the importance of assessing interkingdom associations in soil microbial networks. Overall, this study shows how ecotones can be used as a model to delineate microbial structural patterns and ecological processes across adjoining land-uses within a landscape.}, } @article {pmid30250696, year = {2018}, author = {Smith, TJ and Mayfield, MM}, title = {The effect of habitat fragmentation on the bee visitor assemblages of three Australian tropical rainforest tree species.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8204-8216}, pmid = {30250696}, issn = {2045-7758}, abstract = {Tropical forest loss and fragmentation can change bee community dynamics and potentially interrupt plant-pollinator relationships. While bee community responses to forest fragmentation have been investigated in a number of tropical regions, no studies have focused on this topic in Australia. In this study, we examine taxonomic and functional diversity of bees visiting flowers of three tree species across small and large rainforest fragments in Australian tropical landscapes. We found lower taxonomic diversity of bees visiting flowers of trees in small rainforest fragments compared with large forest fragments and show that bee species in small fragments were subsets of species in larger fragments. Bees visiting trees in small fragments also had higher mean body sizes than those in larger fragments, suggesting that small-sized bees may be less likely to persist in small fragments. Lastly, we found reductions in the abundance of eusocial stingless bees visiting flowers in small fragments compared to large fragments. These results suggest that pollinator visits to native trees living in small tropical forest remnants may be reduced, which may in turn impact on a range of processes, potentially including forest regeneration and diversity maintenance in small forest remnants in Australian tropical countryside landscapes.}, } @article {pmid30250695, year = {2018}, author = {Fisher, HS and Hook, KA and Weber, WD and Hoekstra, HE}, title = {Sibling rivalry: Males with more brothers develop larger testes.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8197-8203}, pmid = {30250695}, issn = {2045-7758}, support = {R00 HD071972/HD/NICHD NIH HHS/United States ; }, abstract = {When females mate with multiple partners in a reproductive cycle, the relative number of competing sperm from rival males is often the most critical factor in determining paternity. Gamete production is directly related to testis size in most species, and is associated with both mating behavior and perceived risk of competition. Deer mice, Peromyscus maniculatus, are naturally promiscuous and males invest significantly more in sperm production than males of P. polionotus, their monogamous sister-species. Here, we show that the larger testes in P. maniculatus are retained after decades of enforced monogamy in captivity. While these results suggest that differences in sperm production between species with divergent evolutionary histories can be maintained in captivity, we also show that the early rearing environment of males can strongly influence their testis size as adults. Using a second-generation hybrid population to increase variation within the population, we show that males reared in litters with more brothers develop larger testes as adults. Importantly, this difference in testis size is also associated with increased fertility. Together, our findings suggest that sperm production may be both broadly shaped by natural selection over evolutionary timescales and also finely tuned during early development.}, } @article {pmid30250694, year = {2018}, author = {Liang, M and Chen, J and Gornish, ES and Bai, X and Li, Z and Liang, C}, title = {Grazing effect on grasslands escalated by abnormal precipitations in Inner Mongolia.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8187-8196}, pmid = {30250694}, issn = {2045-7758}, abstract = {Grazing effects on arid and semi-arid grasslands can be constrained by aridity. Plant functional groups (PFGs) are the most basic component of community structure (CS) and biodiversity & ecosystem function (BEF). They have been suggested as identity-dependent in quantifying the response to grazing intensity and drought severity. Here, we examine how the relationships among PFGs, CS, BEF, and grazing intensity are driven by climatic drought. We conducted a manipulative experiment with three grazing intensities in 2012 (nondrought year) and 2013 (drought year). We classified 62 herbaceous plants into four functional groups based on their life forms. We used the relative species abundance of PFGs to quantify the effects of grazing and drought, and to explore the mechanisms for the pathway correlations using structural equation models (SEM) among PFGs, CS, and BEF directly or indirectly. Grazers consistently favored the perennial forbs (e.g., palatable or nutritious plants), decreasing the plants' relative abundance by 23%-38%. Drought decreased the relative abundance of ephemeral plants by 42 ± 13%; and increased perennial forbs by 20 ± 7% and graminoids by 80 ± 31%. SEM confirmed that annuals and biennials had negative correlations with the other three PFGs, with perennial bunchgrasses facilitated by perennial rhizome grass. Moreover, the contributions of grazing to community structure (i.e., canopy height) were 1.6-6.1 times those from drought, whereas drought effect on community species richness was 3.6 times of the grazing treatment. Lastly, the interactive effects of grazing and drought on BEF were greater than either alone; particularly, drought escalated grazing damage on primary production. Synthesis. The responses of PFGs, CS, and BEF to grazing and drought were identity-dependent, suggesting that grazing and drought regulation of plant functional groups might be a way to shape ecosystem structure and function in grasslands.}, } @article {pmid30250693, year = {2018}, author = {Czarnomska, SD and Niedziałkowska, M and Borowik, T and Jędrzejewska, B}, title = {Regional and local patterns of genetic variation and structure in yellow-necked mice - the roles of geographic distance, population abundance, and winter severity.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8171-8186}, pmid = {30250693}, issn = {2045-7758}, abstract = {The goal of this study, conducted in seven large woodlands and three areas with small woodlots in northeastern Poland in 2004-2008, was to infer genetic structure in yellow-necked mouse Apodemus flavicollis population and to evaluate the roles of environmental and population ecology variables in shaping the spatial pattern of genetic variation using 768 samples genotyped at 13 microsatellite loci. Genetic variation was very high in all studied regions. The primal genetic subdivision was observed between the northern and the southern parts of the study area, which harbored two major clusters and the intermediate area of highly admixed individuals. The probability of assignment of individual mice to the northern cluster increased significantly with lower temperatures of January and July and declined in regions with higher proportion of deciduous and mixed forests. Despite the detected structure, genetic differentiation among regions was very low. Fine-scale structure was shaped by the population density, whereas higher level structure was mainly shaped by geographic distance. Genetic similarity indices were highly influenced by mouse abundance (which positively correlated with the share of deciduous forests in the studied regions) and exhibited the greatest change between 0 and 1 km in the forests, 0 and 5 km in small woodlots. Isolation by distance pattern, calculated among regions, was highly significant but such relationship between genetic and geographic distance was much weaker, and held the linearity at very fine scale (~1.5 km), when analyses were conducted at individual level.}, } @article {pmid30250692, year = {2018}, author = {Gawryszewski, FM}, title = {Color vision models: Some simulations, a general n-dimensional model, and the colourvision R package.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8159-8170}, pmid = {30250692}, issn = {2045-7758}, abstract = {The development of color vision models has allowed the appraisal of color vision independent of the human experience. These models are now widely used in ecology and evolution studies. However, in common scenarios of color measurement, color vision models may generate spurious results. Here I present a guide to color vision modeling (Chittka (1992, Journal of Comparative Physiology A, 170, 545) color hexagon, Endler & Mielke (2005, Journal Of The Linnean Society, 86, 405) model, and the linear and log-linear receptor noise limited models (Vorobyev & Osorio 1998, Proceedings of the Royal Society B, 265, 351; Vorobyev et al. 1998, Journal of Comparative Physiology A, 183, 621)) using a series of simulations, present a unified framework that extends and generalize current models, and provide an R package to facilitate the use of color vision models. When the specific requirements of each model are met, between-model results are qualitatively and quantitatively similar. However, under many common scenarios of color measurements, models may generate spurious values. For instance, models that log-transform data and use relative photoreceptor outputs are prone to generate spurious outputs when the stimulus photon catch is smaller than the background photon catch; and models may generate unrealistic predictions when the background is chromatic (e.g. leaf reflectance) and the stimulus is an achromatic low reflectance spectrum. Nonetheless, despite differences, all three models are founded on a similar set of assumptions. Based on that, I provide a new formulation that accommodates and extends models to any number of photoreceptor types, offers flexibility to build user-defined models, and allows users to easily adjust chromaticity diagram sizes to account for changes when using different number of photoreceptors.}, } @article {pmid30250691, year = {2018}, author = {Lindh, M and Falster, DS and Zhang, L and Dieckmann, U and Brännström, Å}, title = {Latitudinal effects on crown shape evolution.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8149-8158}, pmid = {30250691}, issn = {2045-7758}, abstract = {Large variations in crown shape are observed across the globe, from plants with wide and deep crowns to those with leaves clustered at the top. While there have been advances in the large-scale monitoring of forests, little is known about factors driving variations in crown shape with environmental conditions. Previous theoretical research suggests a gradient in crown shape with latitude, due to the effects of sun angle. Yet, it remains unclear whether such changes are also predicted under competition. Using a size-structured forest-growth model that incorporates self-shading from plants and competitive shading from their neighbors, we investigate how changes in site productivity and sun angle shape crown evolution. We consider evolution in two traits describing the top-heaviness and width-to-height ratio of crowns, shaped by trade-offs reflecting the costs and benefits of alternative architectures. In top-heavy trees, most of the leaves are at the top half of the trunk. We show that, contrary to common belief, the angle of sun beams per se has only a weak influence on crown shapes, except at low site productivity. By contrast, reduced site productivity has a strong effect, with trees growing in less productive sites keeping their leaves closer to the ground. The crown width-to-height ratio is generally higher at a lower site productivity, but this trait is not strongly influenced by any environmental factor. This theoretical analysis brings into question established beliefs about the effects of latitude on crown shapes. By introducing geometry-related growth constraints caused by shading from both the surrounding forest and the tree on itself, and costs for constructing and maintaining a three-dimensional crown, our analysis suggests crown shapes may vary with latitude, mostly via effects on overall site productivity, and less because of the angle of the sun.}, } @article {pmid30250690, year = {2018}, author = {Hu, M and Liu, Y and Sun, Z and Zhang, K and Liu, Y and Miao, R and Wan, S}, title = {Fire rather than nitrogen addition affects understory plant communities in the short term in a coniferous-broadleaf mixed forest.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8135-8148}, pmid = {30250690}, issn = {2045-7758}, abstract = {Increasing fire risk and atmospheric nitrogen (N) deposition have the potential to alter plant community structure and composition, with consequent impacts on biodiversity and ecosystem functioning. This study was conducted to examine short-term responses of understory plant community to burning and N addition in a coniferous-broadleaved mixed forest of the subtropical-temperate transition zone in Central China. The experiment used a pair-nested design, with four treatments (control, burning, N addition, and burning plus N addition) and five replicates. Species richness, cover, and density of woody and herbaceous plants were monitored for 3 years after a low-severity fire in the spring of 2014. Burning, but not N addition, significantly stimulated the cover (+15.2%, absolute change) and density (+62.8%) of woody species as well as herb richness (+1.2 species/m2, absolute change), cover (+25.5%, absolute change), and density (+602.4%) across the seven sampling dates from June 2014 to October 2016. Light availability, soil temperature, and prefire community composition could be primarily responsible for the understory community recovery after the low-severity fire. The observations suggest that light availability and soil temperature are more important than nutrients in structuring understory plant community in the mixed forest of the subtropical-temperate transition zone in Central China. Legacy woody and herb species dominated the understory vegetation over the 3 years after fire, indicating strong resistance and resilience of forest understory plant community and biodiversity to abrupt environmental perturbation.}, } @article {pmid30250689, year = {2018}, author = {Wacker, S and Larsen, BM and Jakobsen, P and Karlsson, S}, title = {High levels of multiple paternity in a spermcast mating freshwater mussel.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8126-8134}, pmid = {30250689}, issn = {2045-7758}, abstract = {Multiple paternity is an important characteristic of the genetic mating system and common across a wide range of taxa. Multiple paternity can increase within-population genotypic diversity, allowing selection to act on a wider spectre of genotypes, and potentially increasing effective population size. While the genetic mating system has been studied in many species with active mating behavior, little is known about multiple paternity in sessile species releasing gametes into the water. In freshwater mussels, males release sperm into the water, while eggs are retained and fertilized inside the female (spermcast mating). Mature parasitic glochidia are released into the water and attach to the gills of fish where they are encapsulated until settling in the bottom substrate. We used 15 microsatellite markers to detect multiple paternity in a wild population of the freshwater pearl mussel (Margaritifera margaritifera). We found multiple paternity in all clutches for which more than two offspring were genotyped, and numbers of sires were extremely high. Thirty-two sires had contributed to the largest clutch (43 offspring sampled). This study provides the first evidence of multiple paternity in the freshwater pearl mussel, a species that has experienced dramatic declines across Europe. Previous studies on other species of freshwater mussels have detected much lower numbers of sires. Multiple paternity in freshwater pearl mussels may be central for maintaining genetic variability in small and fragmented populations and for their potential to recover after habitat restoration and may also be important in the evolutionary arms race with their fish host with a much shorter generation time.}, } @article {pmid30250688, year = {2018}, author = {Rosencranz, JA and Thorne, KM and Buffington, KJ and Takekawa, JY and Hechinger, RF and Stewart, TE and Ambrose, RF and MacDonald, GM and Holmgren, MA and Crooks, JA and Patton, RT and Lafferty, KD}, title = {Sea-level rise, habitat loss, and potential extirpation of a salt marsh specialist bird in urbanized landscapes.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8115-8125}, pmid = {30250688}, issn = {2045-7758}, abstract = {Sea-level rise (SLR) impacts on intertidal habitat depend on coastal topology, accretion, and constraints from surrounding development. Such habitat changes might affect species like Belding's savannah sparrows (Passerculus sandwichensis beldingi; BSSP), which live in high-elevation salt marsh in the Southern California Bight. To predict how BSSP habitat might change under various SLR scenarios, we first constructed a suitability model by matching bird observations with elevation. We then mapped current BSSP breeding and foraging habitat at six estuarine sites by applying the elevation-suitability model to digital elevation models. To estimate changes in digital elevation models under different SLR scenarios, we used a site-specific, one-dimensional elevation model (wetland accretion rate model of ecosystem resilience). We then applied our elevation-suitability model to the projected digital elevation models. The resulting maps suggest that suitable breeding and foraging habitat could decline as increased inundation converts middle- and high-elevation suitable habitat to mudflat and subtidal zones. As a result, the highest SLR scenario predicted that no suitable breeding or foraging habitat would remain at any site by 2100 and 2110. Removing development constraints to facilitate landward migration of high salt marsh, or redistributing dredge spoils to replace submerged habitat, might create future high salt marsh habitat, thereby reducing extirpation risk for BSSP in southern California.}, } @article {pmid30250687, year = {2018}, author = {Chen, J and Ni, P and Tran Thi, TN and Kamaldinov, EV and Petukhov, VL and Han, J and Liu, X and Šprem, N and Zhao, S}, title = {Selective constraints in cold-region wild boars may defuse the effects of small effective population size on molecular evolution of mitogenomes.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8102-8114}, pmid = {30250687}, issn = {2045-7758}, abstract = {Spatial range expansion during population colonization is characterized by demographic events that may have significant effects on the efficiency of natural selection. Population genetics suggests that genetic drift brought by small effective population size (Ne) may undermine the efficiency of selection, leading to a faster accumulation of nonsynonymous mutations. However, it is still unknown whether this effect might be balanced or even reversed by strong selective constraints. Here, we used wild boars and local domestic pigs from tropical (Vietnam) and subarctic region (Siberia) as animal model to evaluate the effects of functional constraints and genetic drift on shaping molecular evolution. The likelihood-ratio test revealed that Siberian clade evolved significantly different from Vietnamese clades. Different datasets consistently showed that Siberian wild boars had lower Ka/Ks ratios than Vietnamese samples. The potential role of positive selection for branches with higher Ka/Ks was evaluated using branch-site model comparison. No signal of positive selection was found for the higher Ka/Ks in Vietnamese clades, suggesting the interclade difference was mainly due to the reduction in Ka/Ks for Siberian samples. This conclusion was further confirmed by the result from a larger sample size, among which wild boars from northern Asia (subarctic and nearby region) had lower Ka/Ks than those from southern Asia (temperate and tropical region). The lower Ka/Ks might be due to either stronger functional constraints, which prevent nonsynonymous mutations from accumulating in subarctic wild boars, or larger Ne in Siberian wild boars, which can boost the efficacy of purifying selection to remove functional mutations. The latter possibility was further ruled out by the Bayesian skyline plot analysis, which revealed that historical Ne of Siberian wild boars was smaller than that of Vietnamese wild boars. Altogether, these results suggest stronger functional constraints acting on mitogenomes of subarctic wild boars, which may provide new insights into their local adaptation of cold resistance.}, } @article {pmid30250686, year = {2018}, author = {da Silva, FM and Miño, CI and Izbicki, R and Del Lama, SN}, title = {Considerations for monitoring population trends of colonial waterbirds using the effective number of breeders and census estimates.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8088-8101}, pmid = {30250686}, issn = {2045-7758}, abstract = {Detecting trends in population size fluctuations is a major focus in ecology, evolution, and conservation biology. Populations of colonial waterbirds have been monitored using demographic approaches to determine annual census size (Na). We propose the addition of genetic estimates of the effective number of breeders (Nb) as indirect measures of the risk of loss of genetic diversity to improve the evaluation of demographics and increase the accuracy of trend estimates in breeding colonies. Here, we investigated which methods of the estimation of Nb are more precise under conditions of moderate genetic diversity, limited sample sizes and few microsatellite loci, as often occurs with natural populations. We used the wood stork as a model species and we offered a workflow that researchers can follow for monitoring bird breeding colonies. Our approach started with simulations using five estimators of Nb and the theoretical results were validated with empirical data collected from breeding colonies settled in the Brazilian Pantanal wetland. In parallel, we estimated census size using a corrected method based on counting active nests. Both in simulations and in natural populations, the approximate Bayesian computation (ABC) and sibship assignment (SA) methods yielded more precise estimates than the linkage disequilibrium, heterozygosity excess, and molecular coancestry methods. In particular, the ABC method performed best with few loci and small sample sizes, while the other estimators required larger sample sizes and at least 13 loci to not underestimate Nb. Moreover, according to our Nb/Na estimates (values were often ≤0.1), the wood stork colonies evaluated could be facing the loss of genetic diversity. We demonstrate that the combination of genetic and census estimates is a useful approach for monitoring natural breeding bird populations. This methodology has been recommended for populations of rare species or with a known history of population decline to support conservation efforts.}, } @article {pmid30250685, year = {2018}, author = {Brattli, MB and Egeland, TB and Nordeide, JT and Folstad, I}, title = {Spawning behavior of Arctic charr (Salvelinus alpinus): Spawning synchrony, vibrational communication, and mate guarding.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8076-8087}, pmid = {30250685}, issn = {2045-7758}, abstract = {A mismatch in synchrony between male and female gamete release in external fertilizers can result in reduced or failed fertilization, sperm competition, and reduced paternity. In Arctic charr (Salvelinus alpinus), males can adopt either a guard or sneak tactic resulting in both pre- and postcopulatory competition between males with alternative reproduction tactics. Here, spawning behavior of free-living Arctic charr was video-recorded, and their reproductive behavior was analyzed. From evaluating 157 spawning events, we observed that females mainly spawned with a guarding male and that the female and the guarding male synchronized timing of gamete release under sperm competition. Although sneakers spawned with higher synchrony than the guarding male in single-male spawning events, the average sneaker released his milt less synchronized with the female than the guarding male under sperm competition. Approximately 50% of the recorded spawning events occurred under sperm competition, where each event included an average of 2.7 males. Additionally, sneakers were more exposed to sperm competition than guarding males. An influx of males, in close proximity to the female, occurred during the behavioral sequences leading up to egg release, but this influx seemed not dependent on egg release, suggesting that something else than gonadal product attracts sneaker males to the spawning female. Just before and during the actual release of gametes, the spawning couple vibrates their bodies in close contact and it seems likely that this vibrational communication between the spawning couple, which results in a larger amplitude sound wave than seen under regular courting, reveals time of gamete release to sneaker males. Thus, vibrational communication may enable synchrony between the guarding male and the female, and this might be traded against the cost of higher detectability from surrounding sneaker males, eavesdropping in close proximity.}, } @article {pmid30250684, year = {2018}, author = {Wang, D and Pentzold, S and Kunert, M and Groth, M and Brandt, W and Pasteels, JM and Boland, W and Burse, A}, title = {A subset of chemosensory genes differs between two populations of a specialized leaf beetle after host plant shift.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8055-8075}, pmid = {30250684}, issn = {2045-7758}, abstract = {Due to its fundamental role in shaping host selection behavior, we have analyzed the chemosensory repertoire of Chrysomela lapponica. This specialized leaf beetle evolved distinct populations which shifted from the ancestral host plant, willow (Salix sp., Salicaceae), to birch (Betula rotundifolia, Betulaceae). We identified 114 chemosensory candidate genes in adult C. lapponica: 41 olfactory receptors (ORs), eight gustatory receptors, 17 ionotropic receptors, four sensory neuron membrane proteins, 32 odorant binding proteins (OBPs), and 12 chemosensory proteins (CSP) by RNA-seq. Differential expression analyses in the antennae revealed significant upregulation of one minus-C OBP (Clap OBP27) and one CSP (Clap CSP12) in the willow feeders. In contrast, one OR (Clap OR17), four minus-C OBPs (Clap OBP02, 07, 13, 20), and one plus-C OBP (Clap OBP32) were significantly upregulated in birch feeders. The differential expression pattern in the legs was more complex. To narrow down putative ligands acting as cues for host discrimination, the relative abundance and diversity of volatiles of the two host plant species were analyzed. In addition to salicylaldehyde (willow-specific), both plant species differed mainly in their emission rate of terpenoids such as (E,E)-α-farnesene (high in willow) or 4,8-dimethylnona-1,3,7-triene (high in birch). Qualitatively, the volatiles were similar between willow and birch leaves constituting an "olfactory bridge" for the beetles. Subsequent structural modeling of the three most differentially expressed OBPs and docking studies using 22 host volatiles indicated that ligands bind with varying affinity. We suggest that the evolution of particularly minus-C OBPs and ORs in C. lapponica facilitated its host plant shift via chemosensation of the phytochemicals from birch as novel host plant.}, } @article {pmid30250683, year = {2018}, author = {Koontz, MJ and Oldfather, MF and Melbourne, BA and Hufbauer, RA}, title = {Parsing propagule pressure: Number, not size, of introductions drives colonization success in a novel environment.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8043-8054}, pmid = {30250683}, issn = {2045-7758}, abstract = {Predicting whether individuals will colonize a novel habitat is of fundamental ecological interest and is crucial to conservation efforts. A consistently supported predictor of colonization success is the number of individuals introduced, also called propagule pressure. Propagule pressure increases with the number of introductions and the number of individuals per introduction (the size of the introduction), but it is unresolved which process is a stronger driver of colonization success. Furthermore, their relative importance may depend upon the environment, with multiple introductions potentially enhancing colonization of fluctuating environments. To evaluate the relative importance of the number and size of introductions and its dependence upon environmental variability, we paired demographic simulations with a microcosm experiment. Using Tribolium flour beetles as a model system, we introduced a fixed number of individuals into replicated novel habitats of stable or fluctuating quality, varying the number of introductions through time and size of each introduction. We evaluated establishment probability and the size of extant populations through seven generations. We found that establishment probability generally increased with more, smaller introductions, but was not affected by biologically realistic fluctuations in environmental quality. Population size was not significantly affected by environmental variability in the simulations, but populations in the microcosms grew larger in a stable environment, especially with more introduction events. In general, the microcosm experiment yielded higher establishment probability and larger populations than the demographic simulations. We suggest that genetic mechanisms likely underlie these differences and thus deserve more attention in efforts to parse propagule pressure. Our results highlight the importance of preventing further introductions of undesirable species to invaded sites and suggest conservation efforts should focus on increasing the number of introductions or reintroductions of desirable species rather than increasing the size of those introduction events into harsh environments.}, } @article {pmid30250682, year = {2018}, author = {Escobar, S and Pintaud, JC and Balslev, H and Bernal, R and Moraes Ramírez, M and Millán, B and Montúfar, R}, title = {Genetic structuring in a Neotropical palm analyzed through an Andean orogenesis-scenario.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8030-8042}, pmid = {30250682}, issn = {2045-7758}, abstract = {Andean orogenesis has driven the development of very high plant diversity in the Neotropics through its impact on landscape evolution and climate. The analysis of the intraspecific patterns of genetic structure in plants would permit inferring the effects of Andean uplift on the evolution and diversification of Neotropical flora. In this study, using microsatellite markers and Bayesian clustering analyses, we report the presence of four genetic clusters for the palm Oenocarpus bataua var. bataua which are located within four biogeographic regions in northwestern South America: (a) Chocó rain forest, (b) Amotape-Huancabamba Zone, (c) northwestern Amazonian rain forest, and (d) southwestern Amazonian rain forest. We hypothesize that these clusters developed following three genetic diversification events mainly promoted by Andean orogenic events. Additionally, the distinct current climate dynamics among northwestern and southwestern Amazonia may maintain the genetic diversification detected in the western Amazon basin. Genetic exchange was identified between the clusters, including across the Andes region, discarding the possibility of any cluster to diversify as a distinct intraspecific variety. We identified a hot spot of genetic diversity in the northern Peruvian Amazon around the locality of Iquitos. We also detected a decrease in diversity with distance from this area in westward and southward direction within the Amazon basin and the eastern Andean foothills. Additionally, we confirmed the existence and divergence of O. bataua var. bataua from var. oligocarpus in northern South America, possibly expanding the distributional range of the latter variety beyond eastern Venezuela, to the central and eastern Andean cordilleras of Colombia. Based on our results, we suggest that Andean orogenesis is the main driver of genetic structuring and diversification in O. bataua within northwestern South America.}, } @article {pmid30250681, year = {2018}, author = {Gómez, J and Ramo, C and Stevens, M and Liñán-Cembrano, G and Rendón, MA and Troscianko, JT and Amat, JA}, title = {Latitudinal variation in biophysical characteristics of avian eggshells to cope with differential effects of solar radiation.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8019-8029}, pmid = {30250681}, issn = {2045-7758}, abstract = {Solar radiation is an important driver of animal coloration, not only because of the effects of coloration on body temperature but also because coloration may protect from the deleterious effects of UV radiation. Indeed, dark coloration may protect from UV, but may increase the risk of overheating. In addition, the effect of coloration on thermoregulation should change with egg size, as smaller eggs have higher surface-volume ratios and greater convective coefficients than larger eggs, so that small eggs can dissipate heat quickly. We tested whether the reflectance of eggshells, egg spottiness, and egg size of the ground-nesting Kentish plover Charadrius alexandrinus is affected by maximum ambient temperature and solar radiation at breeding sites. We measured reflectance, both in the UV and human visible spectrum, spottiness, and egg size in photographs from a museum collection of plover eggshells. Eggshells of lower reflectance (darker) were found at higher latitudes. However, in southern localities where solar radiation is very high, eggshells are also of dark coloration. Eggshell coloration had no significant relationship with ambient temperature. Spotiness was site-specific. Small eggs tended to be light-colored. Thermal constraints may drive the observed spatial variation in eggshell coloration, which may be lighter in lower latitudes to diminish the risk of overheating as a result of higher levels of solar radiation. However, in southern localities with very high levels of UV radiation, eggshells are of dark coloration likely to protect embryos from more intense UV radiation. Egg size exhibited variation in relation to coloration, likely through the effect of surface area-to-volume ratios on overheating and cooling rates of eggs. Therefore, differential effects of solar radiation on functions of coloration and size of eggshells may shape latitudinal variations in egg appearance in the Kentish plover.}, } @article {pmid30250680, year = {2018}, author = {Khorozyan, I and Ghoddousi, S and Soufi, M and Soofi, M and Waltert, M}, title = {Cattle selectivity by leopards suggests ways to mitigate human-leopard conflict.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8011-8018}, pmid = {30250680}, issn = {2045-7758}, abstract = {Addressing widespread livestock losses to carnivores requires information on which livestock categories are preferentially selected. We analyzed an individual-based database of cattle grazing in forest (n = 932) and having been killed (n = 70) by leopards (Panthera pardus) in the Hyrcanian forest, Iran. We calculated Jacobs' selectivity index for cattle age, sex, and coloration across four scales: the study area as a whole, three sites, nine villages, and 60 cattle owners. Naturally colored cattle were significantly preferred by leopards at all scales in comparison with black and black-and-white cattle, and there was also a preference for males and juveniles at the study area level. More research is needed to see whether cattle losses would decrease if the share of naturally colored individuals in local holdings was reduced and males and juveniles had limited access to forest. We conclude that phenotypic and biologic characteristics of livestock can affect depredation and appeal for more research in this direction, particularly within the predator-prey framework.}, } @article {pmid30250679, year = {2018}, author = {Dotsev, AV and Deniskova, TE and Okhlopkov, IM and Mészáros, G and Sölkner, J and Reyer, H and Wimmers, K and Brem, G and Zinovieva, NA}, title = {Genome-wide SNP analysis unveils genetic structure and phylogeographic history of snow sheep (Ovis nivicola) populations inhabiting the Verkhoyansk Mountains and Momsky Ridge (northeastern Siberia).}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {8000-8010}, pmid = {30250679}, issn = {2045-7758}, abstract = {Insights into the genetic characteristics of a species provide important information for wildlife conservation programs. Here, we used the OvineSNP50 BeadChip developed for domestic sheep to examine population structure and evaluate genetic diversity of snow sheep (Ovis nivicola) inhabiting Verkhoyansk Range and Momsky Ridge. A total of 1,121 polymorphic SNPs were used to test 80 specimens representing five populations, including four populations of the Verkhoyansk Mountain chain: Kharaulakh Ridge-Tiksi Bay (TIK, n = 22), Orulgan Ridge (ORU, n = 22), the central part of Verkhoyansk Range (VER, n = 15), Suntar-Khayata Ridge (SKH, n = 13), and Momsky Ridge (MOM, n = 8). We showed that the studied populations were genetically structured according to a geographic pattern. Pairwise FST values ranged from 0.044 to 0.205. Admixture analysis identified K = 2 as the most likely number of ancestral populations. A Neighbor-Net tree showed that TIK was an isolated group related to the main network through ORU. TreeMix analysis revealed that TIK and MOM originated from two different ancestral populations and detected gene flow from MOM to ORU. This was supported by the f3 statistic, which showed that ORU is an admixed population with TIK and MOM/SKH heritage. Genetic diversity in the studied groups was increasing southward. Minimum values of observed (Ho) and expected (He) heterozygosity and allelic richness (Ar) were observed in the most northern population-TIK, and maximum values were observed in the most southern population-SKH. Thus, our results revealed clear genetic structure in the studied populations of snow sheep and showed that TIK has a different origin from MOM, SKH, and VER even though they are conventionally considered a single subspecies known as Yakut snow sheep (Ovis nivicola lydekkeri). Most likely, TIK was an isolated group during the Late Pleistocene glaciations of Verkhoyansk Range.}, } @article {pmid30250678, year = {2018}, author = {Yang, J and Zhou, S and Huang, D and He, X}, title = {Phylogeography of two closely related species of Allium endemic to East Asia: Population evolution in response to climate oscillations.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7986-7999}, pmid = {30250678}, issn = {2045-7758}, abstract = {This study investigated the effects of climate oscillations on the evolution of two closely related Allium species, A. neriniflorum and A. tubiflorum. We sequenced three cp DNA (cpDNA) fragments (rps16, rpl32-trnL, and trnD-trnT, together approximately 2,500 bp in length) of two closely related Allium species, with samples from 367 individuals in 47 populations distributed across the total range of these species. The interspecific and intraspecific divergence times of the two species were in the Quaternary glaciation. The population divergence was high for the cpDNA variation, suggesting a significant phylogeographic structure (NST = 0.844, GST = 0.798, p < 0.05). Remarkable ecological differentiation was also revealed by Niche models and statistical analyses. Our results suggest the speciation event of the two species was triggered by violent climatic changes during the Quaternary glaciation.}, } @article {pmid30250677, year = {2018}, author = {Rundlöf, M and Lundin, O and Bommarco, R}, title = {Annual flower strips support pollinators and potentially enhance red clover seed yield.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7974-7985}, pmid = {30250677}, issn = {2045-7758}, abstract = {Ecological intensification provides opportunity to increase agricultural productivity while minimizing negative environmental impacts, by supporting ecosystem services such as crop pollination and biological pest control. For this we need to develop targeted management solutions that provide critical resources to service-providing organisms at the right time and place. We tested whether annual strips of early flowering phacelia Phacelia tanacetifolia support pollinators and natural enemies of seed weevils Protapion spp., by attracting and offering nectar and pollen before the crop flowers. This was expected to increase yield of red clover Trifolium pratense seed. We monitored insect pollinators, pests, natural enemies and seed yields in a total of 50 clover fields along a landscape heterogeneity gradient, over 2 years and across two regions in southern Sweden. About half of the fields were sown with flower strips of 125-2,000 m2. The clover fields were pollinated by 60% bumble bees Bombus spp. and 40% honey bees Apis mellifera. The clover seed yield was negatively associated with weevil density, but was unrelated to bee species richness and density. Flower strips enhanced bumble bees species richness in the clover fields, with the strongest influence in heterogeneous landscapes. There were few detectable differences between crop fields with and without flower strips. However, long-tongued bumble bees were redistributed toward field interiors and during phacelia bloom honey bees toward field edges. Clover seed yield also increased with increasing size of the flower strip. We conclude that annual flower strips of early flower resources can support bumble bee species richness and, if sufficiently large, possibly also increase crop yields. However, clover seed yield was mainly limited by weevil infestation, which was not influenced by the annual flower strips. A future goal should be to design targeted measures for pest control.}, } @article {pmid30250676, year = {2018}, author = {Briggs, HM and Graham, S and Switzer, CM and Hopkins, R}, title = {Variation in context-dependent foraging behavior across pollinators.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7964-7973}, pmid = {30250676}, issn = {2045-7758}, abstract = {Pollinator foraging behavior has direct consequences for plant reproduction and has been implicated in driving floral trait evolution. Exploring the degree to which pollinators exhibit flexibility in foraging behavior will add to a mechanistic understanding of how pollinators can impose selection on plant traits. Although plants have evolved suites of floral traits to attract pollinators, flower color is a particularly important aspect of the floral display. Some pollinators show strong innate color preference, but many pollinators display flexibility in preference due to learning associations between rewards and color, or due to variable perception of color in different environments or plant communities. This study examines the flexibility in flower color preference of two groups of native butterfly pollinators under natural field conditions. We find that pipevine swallowtails (Battus philenor) and skippers (family Hesperiidae), the predominate pollinators of the two native Texas Phlox species, Phlox cuspidata and Phlox drummondii, display distinct patterns of color preferences across different contexts. Pipevine swallowtails exhibit highly flexible color preferences and likely utilize other floral traits to make foraging decisions. In contrast, skippers have consistent color preferences and likely use flower color as a primary cue for foraging. As a result of this variation in color preference flexibility, the two pollinator groups impose concordant selection on flower color in some contexts but discordant selection in other contexts. This variability could have profound implications for how flower traits respond to pollinator-mediated selection. Our findings suggest that studying dynamics of behavior in natural field conditions is important for understanding plant-pollinator interactions.}, } @article {pmid30250675, year = {2018}, author = {Barbian, HJ and Connell, AJ and Avitto, AN and Russell, RM and Smith, AG and Gundlapally, MS and Shazad, AL and Li, Y and Bibollet-Ruche, F and Wroblewski, EE and Mjungu, D and Lonsdorf, EV and Stewart, FA and Piel, AK and Pusey, AE and Sharp, PM and Hahn, BH}, title = {CHIIMP: An automated high-throughput microsatellite genotyping platform reveals greater allelic diversity in wild chimpanzees.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7946-7963}, pmid = {30250675}, issn = {2045-7758}, support = {T32 AI007632/AI/NIAID NIH HHS/United States ; R37 AI050529/AI/NIAID NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; R01 AI120810/AI/NIAID NIH HHS/United States ; R01 AI091595/AI/NIAID NIH HHS/United States ; T32 AI055400/AI/NIAID NIH HHS/United States ; }, abstract = {Short tandem repeats (STRs), also known as microsatellites, are commonly used to noninvasively genotype wild-living endangered species, including African apes. Until recently, capillary electrophoresis has been the method of choice to determine the length of polymorphic STR loci. However, this technique is labor intensive, difficult to compare across platforms, and notoriously imprecise. Here we developed a MiSeq-based approach and tested its performance using previously genotyped fecal samples from long-term studied chimpanzees in Gombe National Park, Tanzania. Using data from eight microsatellite loci as a reference, we designed a bioinformatics platform that converts raw MiSeq reads into locus-specific files and automatically calls alleles after filtering stutter sequences and other PCR artifacts. Applying this method to the entire Gombe population, we confirmed previously reported genotypes, but also identified 31 new alleles that had been missed due to sequence differences and size homoplasy. The new genotypes, which increased the allelic diversity and heterozygosity in Gombe by 61% and 8%, respectively, were validated by replicate amplification and pedigree analyses. This demonstrated inheritance and resolved one case of an ambiguous paternity. Using both singleplex and multiplex locus amplification, we also genotyped fecal samples from chimpanzees in the Greater Mahale Ecosystem in Tanzania, demonstrating the utility of the MiSeq-based approach for genotyping nonhabituated populations and performing comparative analyses across field sites. The new automated high-throughput analysis platform (available at https://github.com/ShawHahnLab/chiimp) will allow biologists to more accurately and effectively determine wildlife population size and structure, and thus obtain information critical for conservation efforts.}, } @article {pmid30250674, year = {2018}, author = {Okuyama, T}, title = {Stage duration distributions in matrix population models.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7936-7945}, pmid = {30250674}, issn = {2045-7758}, abstract = {Matrix population models are a standard tool for studying stage-structured populations, but they are not flexible in describing stage duration distributions. This study describes a method for modeling various such distributions in matrix models. The method uses a mixture of two negative binomial distributions (parametrized using a maximum likelihood method) to approximate a target (true) distribution. To examine the performance of the method, populations consisting of two life stages (juvenile and adult) were considered. The juvenile duration distribution followed a gamma distribution, lognormal distribution, or zero-truncated (over-dispersed) Poisson distribution, each of which represents a target distribution to be approximated by a mixture distribution. The true population growth rate based on a target distribution was obtained using an individual-based model, and the extent to which matrix models can approximate the target dynamics was examined. The results show that the method generally works well for the examined target distributions, but is prone to biased predictions under some conditions. In addition, the method works uniformly better than an existing method whose performance was also examined for comparison. Other details regarding parameter estimation and model development are also discussed.}, } @article {pmid30250673, year = {2018}, author = {Chardon, NI and Wipf, S and Rixen, C and Beilstein, A and Doak, DF}, title = {Local trampling disturbance effects on alpine plant populations and communities: Negative implications for climate change vulnerability.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7921-7935}, pmid = {30250673}, issn = {2045-7758}, abstract = {Global change is modifying species communities from local to landscape scales, with alterations in the abiotic and biotic determinants of geographic range limits causing species range shifts along both latitudinal and elevational gradients. An important but often overlooked component of global change is the effect of anthropogenic disturbance, and how it interacts with the effects of climate to affect both species and communities, as well as interspecies interactions, such as facilitation and competition. We examined the effects of frequent human trampling disturbances on alpine plant communities in Switzerland, focusing on the elevational range of the widely distributed cushion plant Silene acaulis and the interactions of this facilitator species with other plants. Examining size distributions and densities, we found that disturbance appears to favor individual Silene growth at middle elevations. However, it has negative effects at the population level, as evidenced by a reduction in population density and reproductive indices. Disturbance synergistically interacts with the effects of elevation to reduce species richness at low and high elevations, an effect not mitigated by Silene. In fact, we find predominantly competitive interactions, both by Silene on its hosted and neighboring species and by neighboring (but not hosted) species on Silene. Our results indicate that disturbance can be beneficial for Silene individual performance, potentially through changes in its neighboring species community. However, possible reduced recruitment in disturbed areas could eventually lead to population declines. While other studies have shown that light to moderate disturbances can maintain high species diversity, our results emphasize that heavier disturbance reduces species richness, diversity, as well as percent cover, and adversely affects cushion plants and that these effects are not substantially reduced by plant-plant interactions. Heavily disturbed alpine systems could therefore be at greater risk for upward encroachment of lower elevation species in a warming world.}, } @article {pmid30250672, year = {2018}, author = {Wright, PJ and Régnier, T and Gibb, FM and Augley, J and Devalla, S}, title = {Assessing the role of ontogenetic movement in maintaining population structure in fish using otolith microchemistry.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7907-7920}, pmid = {30250672}, issn = {2045-7758}, abstract = {Identifying the mechanisms maintaining population structure in marine fish species with more than a single dispersing life stage is challenging because of the difficulty in tracking all life stages. Here, a two-stage otolith microchemistry approach to examining life-stage movement was adopted, tracking a year-class from the juvenile to adult stage and inferring larval sources from clustering, in order to consider the mechanisms maintaining population structuring in North Sea cod. Clustering of near-core chemistry identified four clusters, two of which had either a southern or northern affinity and were similar to juvenile edge chemistry. The other two clusters, common to the central North Sea, had intermediate chemical composition and may have reflected either larval mixing in this region or a lack of geographic heterogeneity in the elemental signature. From the comparison of whole juvenile and the corresponding component of adult otoliths, adults from the southern North Sea mostly recruited from adjacent nursery grounds. In contrast, many adults in the northern North Sea had a juvenile chemistry consistent with the Skagerrak and juveniles from the northern Skagerrak site had a near-core chemistry consistent with the northern North Sea. Similarities in otolith chemistry were consistent with retention of early life stages at a regional level and also juvenile and adult fidelity. The links between the northern North Sea and Skagerrak indicate natal homing, which when considered in the context of genetic evidence is suggestive of philopatry. The approach used here should be useful in exploring the mechanisms underlying population structuring in other species with multiple dispersive life stages and calcified hard parts.}, } @article {pmid30250671, year = {2018}, author = {Vasconcelos, TS and do Nascimento, BTM and Prado, VHM}, title = {Expected impacts of climate change threaten the anuran diversity in the Brazilian hotspots.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7894-7906}, pmid = {30250671}, issn = {2045-7758}, abstract = {We performed Ecological Niche Models (ENMs) to generate climatically suitable areas for anurans in the Brazilian hotspots, the Atlantic Forest (AF), and Cerrado (CER), considering the baseline and future climate change scenarios, to evaluate the differences in the alpha and beta diversity metrics across time. We surveyed anuran occurrence records and generated ENMs for 350 and 155 species in the AF and CER. The final predictive maps for the baseline, 2050, and 2070 climate scenarios, based on an ensemble approach, were used to estimate the alpha (local species richness) and beta diversity metrics (local contribution to beta diversity index and its decomposition into replacement and nestedness components) in each ~50 × 50 km grid cell of the hotspots. Climate change is not expected to drastically change the distribution of the anuran richness gradients, but to negatively impact their whole extensions (i.e., cause species losses throughout the hotspots), except the northeastern CER that is expected to gain in species richness. Areas having high beta diversity are expected to decrease in northeastern CER, whereas an increase is expected in southeastern/southwestern CER under climate change. High beta diversity areas are expected to remain in the same AF locations as the prediction of the baseline climate, but the predominance of species loss under climate change is expected to increase the nestedness component in the hotspot. These results suggest that the lack of similar climatically suitable areas for most species will be the main challenge that species will face in the future. Finally, the application of the present framework to a wide range of taxa is an important step for the conservation of threatened biomes.}, } @article {pmid30250670, year = {2018}, author = {Qin, YG and Zhou, QS and Yu, F and Wang, XB and Wei, JF and Zhu, CD and Zhang, YZ and Vogler, AP}, title = {Host specificity of parasitoids (Encyrtidae) toward armored scale insects (Diaspididae): Untangling the effect of cryptic species on quantitative food webs.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7879-7893}, pmid = {30250670}, issn = {2045-7758}, abstract = {Host specificity of parasitoids may be measured by various specialization indices to assess the variation of interaction strength among species and the structure of the wider interaction network. However, the conclusions from analyses at the species and network levels may differ, which remains poorly explored. In addition, the recovery of cryptic species of hosts and parasitoids with molecular data may affect the structure of inferred interaction links. We quantified host specificity of hymenopteran parasitoids (family Encyrtidae) on armored scale insects (Hemiptera: Diaspididae) from a wide geographic sampling range across the Chinese Mainland based on both morphological and molecular species delimitation. Mitochondrial COI and nuclear 28S markers detected high cryptic species diversity in the encyrtids and to a lesser degree in the diaspidids, which divided generalist morphospecies into complexes of specialists and generalists. One-to-one reciprocal host-parasite links were increased in the molecular data set, but different quantitative species-level indices produced contrasting estimates of specificity from various one-to-multiple and multiple-to-multiple host-parasite links. Network indices calculated from DNA-based species, compared to morphology-based species definitions, showed lower connectance and generality, but greater specialization and compartmentalization of the interaction network. We conclude that a high degree of cryptic species in host-parasitoid systems refines the true network structure and may cause us overestimating the stability of these interaction webs.}, } @article {pmid30250669, year = {2018}, author = {Benito, X and Fritz, SC and Steinitz-Kannan, M and Vélez, MI and McGlue, MM}, title = {Lake regionalization and diatom metacommunity structuring in tropical South America.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7865-7878}, pmid = {30250669}, issn = {2045-7758}, abstract = {Lakes and their topological distribution across Earth's surface impose ecological and evolutionary constraints on aquatic metacommunities. In this study, we group similar lake ecosystems as metacommunity units influencing diatom community structure. We assembled a database of 195 lakes from the tropical Andes and adjacent lowlands (8°N-30°S and 58-79°W) with associated environmental predictors to examine diatom metacommunity patterns at two different levels: taxon and functional (deconstructed species matrix by ecological guilds). We also derived spatial variables that inherently assessed the relative role of dispersal. Using complementary multivariate statistical techniques (principal component analysis, cluster analysis, nonmetric multidimensional scaling, Procrustes, variance partitioning), we examined diatom-environment relationships among different lake habitats (sediment surface, periphyton, and plankton) and partitioned community variation to evaluate the influence of niche- and dispersal-based assembly processes in diatom metacommunity structure across lake clusters. The results showed a significant association between geographic clusters of lakes based on gradients of climate and landscape configuration and diatom assemblages. Six lake clusters distributed along a latitudinal gradient were identified as functional metacommunity units for diatom communities. Variance partitioning revealed that dispersal mechanisms were a major contributor to diatom metacommunity structure, but in a highly context-dependent fashion across lake clusters. In the Andean Altiplano and adjacent lowlands of Bolivia, diatom metacommunities are niche assembled but constrained by either dispersal limitation or mass effects, resulting from area, environmental heterogeneity, and ecological guild relationships. Topographic heterogeneity played an important role in structuring planktic diatom metacommunities. We emphasize the value of a guild-based metacommunity model linked to dispersal for elucidating mechanisms underlying latitudinal gradients in distribution. Our findings reveal the importance of shifts in ecological drivers across climatic and physiographically distinct lake clusters, providing a basis for comparison of broad-scale community gradients in lake-rich regions elsewhere. This may help guide future research to explore evolutionary constraints on the rich Neotropical benthic diatom species pool.}, } @article {pmid30250668, year = {2018}, author = {Koch, JB and Vandame, R and Mérida-Rivas, J and Sagot, P and Strange, J}, title = {Quaternary climate instability is correlated with patterns of population genetic variability in Bombus huntii.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7849-7864}, pmid = {30250668}, issn = {2045-7758}, abstract = {Climate oscillations have left a significant impact on the patterns of genetic diversity observed in numerous taxa. In this study, we examine the effect of Quaternary climate instability on population genetic variability of a bumble bee pollinator species, Bombus huntii in western North America. Pleistocene and contemporary B. huntii habitat suitability (HS) was estimated with an environmental niche model (ENM) by associating 1,035 locality records with 10 bioclimatic variables. To estimate genetic variability, we genotyped 380 individuals from 33 localities at 13 microsatellite loci. Bayesian inference was used to examine population structure with and without a priori specification of geographic locality. We compared isolation by distance (IBD) and isolation by resistance (IBR) models to examine population differentiation within and among the Bayesian inferred genetic clusters. Furthermore, we tested for the effect of environmental niche stability (ENS) on population genetic diversity with linear regression. As predicted, high-latitude B. huntii habitats exhibit low ENS when compared to low-latitude habitats. Two major genetic clusters of B. huntii inhabit western North America: (a) a north genetic cluster predominantly distributed north of 28°N and (b) a south genetic cluster distributed south of 28°N. In the south genetic cluser, both IBD and IBR models are significant. However, in the north genetic cluster, IBD is significant but not IBR. Furthermore, the IBR models suggest that low-latitude montane populations are surrounded by habitat with low HS, possibly limiting dispersal, and ultimately gene flow between populations. Finally, we detected high genetic diversity across populations in regions that have been climatically unstable since the last glacial maximum (LGM), and low genetic diversity across populations in regions that have been climatically stable since the LGM. Understanding how species have responded to climate change has the potential to inform management and conservation decisions of both ecological and economic concerns.}, } @article {pmid30250667, year = {2018}, author = {Kotsakiozi, P and Evans, BR and Gloria-Soria, A and Kamgang, B and Mayanja, M and Lutwama, J and Le Goff, G and Ayala, D and Paupy, C and Badolo, A and Pinto, J and Sousa, CA and Troco, AD and Powell, JR}, title = {Population structure of a vector of human diseases: Aedes aegypti in its ancestral range, Africa.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7835-7848}, pmid = {30250667}, issn = {2045-7758}, support = {R01 AI101112/AI/NIAID NIH HHS/United States ; }, abstract = {Aedes aegypti, the major vector of dengue, yellow fever, chikungunya, and Zika viruses, remains of great medical and public health concern. There is little doubt that the ancestral home of the species is Africa. This mosquito invaded the New World 400-500 years ago and later, Asia. However, little is known about the genetic structure and history of Ae. aegypti across Africa, as well as the possible origin(s) of the New World invasion. Here, we use ~17,000 genome-wide single nucleotide polymorphisms (SNPs) to characterize a heretofore undocumented complex picture of this mosquito across its ancestral range in Africa. We find signatures of human-assisted migrations, connectivity across long distances in sylvan populations, and of local admixture between domestic and sylvan populations. Finally, through a phylogenetic analysis combined with the genetic structure analyses, we suggest West Africa and especially Angola as the source of the New World's invasion, a scenario that fits well with the historic record of 16th-century slave trade between Africa and Americas.}, } @article {pmid30250666, year = {2018}, author = {Fischhoff, IR and Burtis, JC and Keesing, F and Ostfeld, RS}, title = {Tritrophic interactions between a fungal pathogen, a spider predator, and the blacklegged tick.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7824-7834}, pmid = {30250666}, issn = {2045-7758}, abstract = {The blacklegged tick Ixodes scapularis is the primary vector for the bacterium causing Lyme disease in eastern North America and for other medically important pathogens. This species is vulnerable to attack by fungal pathogens and arthropod predators, but the impacts of interactions between biocontrol agents have not been examined. The biocontrol agent Met52®, containing the entomopathogenic fungus Metarhizium brunneum (=M. anisopliae), controls blacklegged ticks with efficacy comparable to chemical acaricides. The brush-legged wolf spider Schizocosa ocreata is a predator of I. scapularis that reduces their survival under field conditions. We conducted a field microcosm experiment to assess the compatibility of Met52 and S. ocreata as tick biocontrol agents. We compared the fits of alternative models in predicting survival of unfed (flat) and blood-fed (engorged) nymphs. We found the strongest support for a model that included negative effects of Met52 and S. ocreata on flat nymph survival. We found evidence for interference between biocontrol agents, with Met52 reducing spider survival, but we did not find a significant interaction effect between the two agents on nymph survival. For engorged nymphs, low recovery rates resulted in low statistical power to detect possible effects of biocontrol agents. We found that nymph questing activity was lower when the spider was active above the leaf litter than when the spider was unobserved. This provides the first evidence that predation cues might affect behavior important for tick fitness and pathogen transmission. This study presents field microcosm evidence that the biopesticide Met52 and spider Schizocosa ocreata each reduced survival of blacklegged ticks Ixodes scapularis. Met52 reduced spider survival. Potential interference between Met52 and the spider should be examined at larger scales, where overlap patterns may differ. Ticks were more likely to quest when the spider was inactive, suggesting the ticks changed their behavior to reduce danger.}, } @article {pmid30250665, year = {2018}, author = {Zhang, L and Xi, Z and Wang, M and Guo, X and Ma, T}, title = {Plastome phylogeny and lineage diversification of Salicaceae with focus on poplars and willows.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7817-7823}, pmid = {30250665}, issn = {2045-7758}, abstract = {Phylogenetic relationships and lineage diversification of the family Salicaceae sensu lato (s.l.) remain poorly understood. In this study, we examined phylogenetic relationships between 42 species from six genera based on the complete plastomes. Phylogenetic analyses of 77 protein coding genes of the plastomes produced good resolution of the interrelationships among most sampled species and the recovered clades. Of the sampled genera from the family, Flacourtia was identified as the most basal and the successive clades comprised both Itoa and Poliothyrsis, Idesia, two genera of the Salicaceae sensu stricto (s.s.) (Populus and Salix). Five major subclades were recovered within the Populus clade. These subclades and their interrelationships are largely inconsistent with morphological classifications and molecular phylogeny based on nuclear internal transcribed spacer sequence variations. Two major subclades were identified for the Salix clade. Molecular dating suggested that species diversification of the major subclades in the Populus and Salix clades occurred mainly within the recent Pliocene. In addition, we found that the rpl32 gene was lost and the rps7 gene evolved into a pseudogene multiple times in the sampled genera of the Salicaceae s.l. Compared with previous studies, our results provide a well-resolved phylogeny from the perspective of the plastomes.}, } @article {pmid30250664, year = {2018}, author = {Moraes, MA and Kubota, TYK and Rossini, BC and Marino, CL and Freitas, MLM and Moraes, MLT and da Silva, AM and Cambuim, J and Sebbenn, AM}, title = {Long-distance pollen and seed dispersal and inbreeding depression in Hymenaea stigonocarpa (Fabaceae: Caesalpinioideae) in the Brazilian savannah.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7800-7816}, pmid = {30250664}, issn = {2045-7758}, abstract = {Hymenaea stigonocarpa is a neotropical tree that is economically important due to its high-quality wood; however, because it has been exploited extensively, it is currently considered threatened. Microsatellite loci were used to investigate the pollen and seed dispersal, mating patterns, spatial genetic structure (SGS), genetic diversity, and inbreeding depression in H. stigonocarpa adults, juveniles, and open-pollinated seeds, which were sampled from isolated trees in a pasture and trees within a forest fragment in the Brazilian savannah. We found that the species presented a mixed mating system, with population and individual variations in the outcrossing rate (0.53-1.0). The studied populations were not genetically isolated due to pollen and seed flow between the studied populations and between the populations and individuals located outside of the study area. Pollen and seed dispersal occurred over long distances (>8 km); however, the dispersal patterns were isolated by distance, with a high frequency of mating occurring between near-neighbor trees and seeds dispersed near the parent trees. The correlated mating for individual seed trees was higher within than among fruits, indicating that fruits present a high proportion of full-sibs. Genetic diversity and SGS were similar among the populations, but offspring showed evidence of inbreeding, mainly originating from mating among related trees, which suggests inbreeding depression between the seed and adult stages. Selfing resulted in a higher inbreeding depression than mating among relatives, as assessed through survival and height. As the populations are not genetically isolated, both are important targets for in situ conservation to maintain their genetic diversity; for ex situ conservation, seeds can be collected from at least 78 trees in both populations separated by at least 250 m.}, } @article {pmid30250663, year = {2018}, author = {Lillie, KM and Gese, EM and Atwood, TC and Sonsthagen, SA}, title = {Development of on-shore behavior among polar bears (Ursus maritimus) in the southern Beaufort Sea: inherited or learned?.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7790-7799}, pmid = {30250663}, issn = {2045-7758}, abstract = {Polar bears (Ursus maritimus) are experiencing rapid and substantial changes to their environment due to global climate change. Polar bears of the southern Beaufort Sea (SB) have historically spent most of the year on the sea ice. However, recent reports from Alaska indicate that the proportion of the SB subpopulation observed on-shore during late summer and early fall has increased. Our objective was to investigate whether this on-shore behavior has developed through genetic inheritance, asocial learning, or through social learning. From 2010 to 2013, genetic data were collected from SB polar bears in the fall via hair snags and remote biopsy darting on-shore and in the spring from captures and remote biopsy darting on the sea ice. Bears were categorized as either on-shore or off-shore individuals based on their presence on-shore during the fall. Levels of genetic relatedness, first-order relatives, mother-offspring pairs, and father-offspring pairs were determined and compared within and between the two categories: on-shore versus off-shore. Results suggested transmission of on-shore behavior through either genetic inheritance or social learning as there was a higher than expected number of first-order relatives exhibiting on-shore behavior. Genetic relatedness and parentage data analyses were in concurrence with this finding, but further revealed mother-offspring social learning as the primary mechanism responsible for the development of on-shore behavior. Recognizing that on-shore behavior among polar bears was predominantly transmitted via social learning from mothers to their offspring has implications for future management and conservation as sea ice continues to decline.}, } @article {pmid30250662, year = {2018}, author = {Ferrari, A and Hagedorn, F and Niklaus, PA}, title = {Disentangling effects of air and soil temperature on C allocation in cold environments: A 14C pulse-labelling study with two plant species.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7778-7789}, pmid = {30250662}, issn = {2045-7758}, abstract = {Carbon cycling responses of ecosystems to global warming will likely be stronger in cold ecosystems where many processes are temperature-limited. Predicting these effects is difficult because air and soil temperatures will not change in concert, and will affect above and belowground processes differently. We disentangled above and belowground temperature effects on plant C allocation and deposition of plant C in soils by independently manipulating air and soil temperatures in microcosms planted with either Leucanthemopsis alpina or Pinus mugo seedlings. Daily average temperatures of 4 or 9°C were applied to shoots and independently to roots, and plants pulse-labelled with 14 CO 2. We traced soil CO 2 and 14 CO 2 evolution for 4 days, after which microcosms were destructively harvested and 14C quantified in plant and soil fractions. In microcosms with L. alpina, net 14C uptake was higher at 9°C than at 4°C soil temperature, and this difference was independent of air temperature. In warmer soils, more C was allocated to roots at greater soil depth, with no effect of air temperature. In P. mugo microcosms, assimilate partitioning to roots increased with air temperature, but only when soils were at 9°C. Higher soil temperatures also increased the mean soil depth at which 14C was allocated. Our findings highlight the dependence of C uptake, use, and partitioning on both air and soil temperature, with the latter being relatively more important. The strong temperature-sensitivity of C assimilate use in the roots and rhizosphere supports the hypothesis that cold limitation on C uptake is primarily mediated by reduced sink strength in the roots. We conclude that variations in soil rather than air temperature are going to drive plant responses to warming in cold environments, with potentially large changes in C cycling due to enhanced transfer of plant-derived C to soils.}, } @article {pmid30250661, year = {2018}, author = {Lacoursière-Roussel, A and Howland, K and Normandeau, E and Grey, EK and Archambault, P and Deiner, K and Lodge, DM and Hernandez, C and Leduc, N and Bernatchez, L}, title = {eDNA metabarcoding as a new surveillance approach for coastal Arctic biodiversity.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7763-7777}, pmid = {30250661}, issn = {2045-7758}, abstract = {Because significant global changes are currently underway in the Arctic, creating a large-scale standardized database for Arctic marine biodiversity is particularly pressing. This study evaluates the potential of aquatic environmental DNA (eDNA) metabarcoding to detect Arctic coastal biodiversity changes and characterizes the local spatio-temporal distribution of eDNA in two locations. We extracted and amplified eDNA using two COI primer pairs from ~80 water samples that were collected across two Canadian Arctic ports, Churchill and Iqaluit, based on optimized sampling and preservation methods for remote regions surveys. Results demonstrate that aquatic eDNA surveys have the potential to document large-scale Arctic biodiversity change by providing a rapid overview of coastal metazoan biodiversity, detecting nonindigenous species, and allowing sampling in both open water and under the ice cover by local northern-based communities. We show that DNA sequences of ~50% of known Canadian Arctic species and potential invaders are currently present in public databases. A similar proportion of operational taxonomic units was identified at the species level with eDNA metabarcoding, for a total of 181 species identified at both sites. Despite the cold and well-mixed coastal environment, species composition was vertically heterogeneous, in part due to river inflow in the estuarine ecosystem, and differed between the water column and tide pools. Thus, COI-based eDNA metabarcoding may quickly improve large-scale Arctic biomonitoring using eDNA, but we caution that aquatic eDNA sampling needs to be standardized over space and time to accurately evaluate community structure changes.}, } @article {pmid30250660, year = {2018}, author = {Ruffino, L and Hartley, SE and DeGabriel, JL and Lambin, X}, title = {Population-level manipulations of field vole densities induce subsequent changes in plant quality but no impacts on vole demography.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7752-7762}, pmid = {30250660}, issn = {2045-7758}, abstract = {Grazing-induced changes in plant quality have been suggested to drive the negative delayed density dependence exhibited by many herbivore species, but little field evidence exists to support this hypothesis. We tested a key premise of the hypothesis that reciprocal feedback between vole grazing pressure and the induction of anti-herbivore silicon defenses in grasses drives observed population cycles in a large-scale field experiment in northern England. We repeatedly reduced population densities of field voles (Microtus agrestis) on replicated 1-ha grassland plots at Kielder Forest, northern England, over a period of 1 year. Subsequently, we tested for the impact of past density on vole life history traits in spring, and whether these effects were driven by induced silicon defenses in the voles' major over-winter food, the grass Deschampsia caespitosa. After several months of density manipulation, leaf silicon concentrations diverged and averaged 22% lower on sites where vole density had been reduced, but this difference did not persist beyond the period of the density manipulations. There were no significant effects of our density manipulations on vole body mass, spring population growth rate, or mean date for the onset of spring reproduction the following year. These findings show that grazing by field voles does induce increased silicon defenses in grasses at a landscape scale. However, at the vole densities encountered, levels of plant damage appear to be below those needed to induce changes in silicon levels large and persistent enough to affect vole performance, confirming the threshold effects we have previously observed in laboratory-based studies. Our findings do not support the plant quality hypothesis for observed vole population cycles in northern England, at least over the range of vole densities that now prevail here.}, } @article {pmid30250659, year = {2018}, author = {Farrell, KJ and Carey, CC}, title = {Power, pitfalls, and potential for integrating computational literacy into undergraduate ecology courses.}, journal = {Ecology and evolution}, volume = {8}, number = {16}, pages = {7744-7751}, pmid = {30250659}, issn = {2045-7758}, abstract = {Environmental research requires understanding nonlinear ecological dynamics that interact across multiple spatial and temporal scales. The analysis of long-term and high-frequency sensor data combined with simulation modeling enables interpretation of complex ecological phenomena, and the computational skills needed to conduct these analyses are increasingly being integrated into graduate student training programs in ecology. Despite its importance, however, computational literacy-that is, the ability to harness the power of computer technologies to accomplish tasks-is rarely taught in undergraduate ecology classrooms, representing a major gap in training students to tackle complex environmental challenges. Through our experience developing undergraduate curricula in long-term and high-frequency data analysis and simulation modeling for two environmental science pedagogical initiatives, Project EDDIE (Environmental Data-Driven Inquiry and Exploration) and Macrosystems EDDIE, we have found that students often feel intimidated by computational tasks, which is compounded by the lack of familiarity with software (e.g., R) and the steep learning curves associated with script-based analytical tools. The use of prepackaged, flexible modules that introduce programming as a mechanism to explore environmental datasets and teach inquiry-based ecology, such as those developed for Project EDDIE and Macrosystems EDDIE, can significantly increase students' experience and comfort levels with advanced computational tools. These types of modules in turn provide great potential for empowering students with the computational literacy needed to ask ecological questions and test hypotheses on their own. As continental-scale sensor observatory networks rapidly expand the availability of long-term and high-frequency data, students with the skills to manipulate, visualize, and interpret such data will be well-prepared for diverse careers in data science, and will help advance the future of open, reproducible science in ecology.}, } @article {pmid30250634, year = {2018}, author = {Wang, X and Luo, Y and Liu, D and Wang, J and Wei, S and Zhao, L}, title = {Complete genome sequence of the Robinia pseudoacacia L. symbiont Mesorhizobium amorphae CCNWGS0123.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {18}, pmid = {30250634}, issn = {1944-3277}, abstract = {Mesorhizobium amorphae CCNWGS0123 was isolated in 2006, from effective nodules of Robinia pseudoacacia L. grown in lead-zinc mine tailing site, in Gansu Province, China. M. amorphae CCNWGS0123 is an aerobic, Gram-negative, non-spore-forming rod strain. This paper characterized M. amorphae CCNWGS0123 and presents its complete genome sequence information and genome annotation. The 7,374,589 bp long genome which encodes 7136 protein-coding genes and 63 RNA coding genes, contains one chromosome and four plasmids. Moreover, a chromosome with no gaps was assembled.}, } @article {pmid30250271, year = {2018}, author = {Bertagnolli, AD and Stewart, FJ}, title = {Microbial niches in marine oxygen minimum zones.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {723-729}, doi = {10.1038/s41579-018-0087-z}, pmid = {30250271}, issn = {1740-1534}, abstract = {In the ocean's major oxygen minimum zones (OMZs), oxygen is effectively absent from sea water and life is dominated by microorganisms that use chemicals other than oxygen for respiration. Recent studies that combine advanced genomic and chemical detection methods are delineating the different metabolic niches that microorganisms can occupy in OMZs. Understanding these niches, the microorganisms that inhabit them, and their influence on marine biogeochemical cycles is crucial as OMZs expand with increasing seawater temperatures.}, } @article {pmid30250256, year = {2018}, author = {Parai, R and Mukhopadhyay, S}, title = {Publisher Correction: Xenon isotopic constraints on the history of volatile recycling into the mantle.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {E28}, doi = {10.1038/s41586-018-0572-6}, pmid = {30250256}, issn = {1476-4687}, abstract = {In this Letter, owing to a production error, the arrows in the middle panel of Fig. 1 were wrongly coloured and there were some some typos elsewhere. These errors have been corrected online.}, } @article {pmid30250255, year = {2018}, author = {Fillmore, CM and Xu, C and Desai, PT and Berry, JM and Rowbotham, SP and Lin, YJ and Zhang, H and Marquez, VE and Hammerman, PS and Wong, KK and Kim, CF}, title = {Author Correction: EZH2 inhibition sensitizes BRG1 and EGFR mutant lung tumours to TopoII inhibitors.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {E27}, doi = {10.1038/s41586-018-0580-6}, pmid = {30250255}, issn = {1476-4687}, abstract = {We wish to correct two mutations in Supplementary Table 4 of this Letter. The NCI-H460 cell line was annotated as being mutant for TP53. NCI-H460 has been verified to be TP53 wild type by several sources1. The NCI-H2009 cell line was annotated as being mutant for PIK3CA. As annotated by COSMIC (ref. 24 of the original Letter) and CCLE (ref. 25 of the original Letter), the NCI-H2009 cell line has a mutation in PIK3C3, rather than PIK3CA. The cell line is wild type for PIK3CA. The Supplementary Information of this Amendment contains the corrected Supplementary Table 4. These errors do not affect our conclusions. The original Letter has not been corrected.}, } @article {pmid30250254, year = {2018}, author = {, }, title = {Publisher Correction: Challenging local realism with human choices.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {E23}, doi = {10.1038/s41586-018-0489-0}, pmid = {30250254}, issn = {1476-4687}, abstract = {In the HTML version of this Letter, the corresponding author link (M. W. Mitchell; morgan.mitchell@icfo.eu) was missing and the citation file was empty. The list of consortium authors was duplicated, with spurious superscript numbers, in the Acknowledgements (the PDF version was correct). In addition, in Fig. 2a of this Letter, the label '4', which indicates Vienna in the inset, was inadvertently displaced into Siberia in the main panel. These errors have been corrected online.}, } @article {pmid30250253, year = {2018}, author = {Debnath, S and Yallowitz, AR and McCormick, J and Lalani, S and Zhang, T and Xu, R and Li, N and Liu, Y and Yang, YS and Eiseman, M and Shim, JH and Hameed, M and Healey, JH and Bostrom, MP and Landau, DA and Greenblatt, MB}, title = {Discovery of a periosteal stem cell mediating intramembranous bone formation.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {133-139}, pmid = {30250253}, issn = {1476-4687}, support = {DP5 OD021351/OD/NIH HHS/United States ; }, abstract = {Bone consists of separate inner endosteal and outer periosteal compartments, each with distinct contributions to bone physiology and each maintaining separate pools of cells owing to physical separation by the bone cortex. The skeletal stem cell that gives rise to endosteal osteoblasts has been extensively studied; however, the identity of periosteal stem cells remains unclear1-5. Here we identify a periosteal stem cell (PSC) that is present in the long bones and calvarium of mice, displays clonal multipotency and self-renewal, and sits at the apex of a differentiation hierarchy. Single-cell and bulk transcriptional profiling show that PSCs display transcriptional signatures that are distinct from those of other skeletal stem cells and mature mesenchymal cells. Whereas other skeletal stem cells form bone via an initial cartilage template using the endochondral pathway4, PSCs form bone via a direct intramembranous route, providing a cellular basis for the divergence between intramembranous versus endochondral developmental pathways. However, there is plasticity in this division, as PSCs acquire endochondral bone formation capacity in response to injury. Genetic blockade of the ability of PSCs to give rise to bone-forming osteoblasts results in selective impairments in cortical bone architecture and defects in fracture healing. A cell analogous to mouse PSCs is present in the human periosteum, raising the possibility that PSCs are attractive targets for drug and cellular therapy for skeletal disorders. The identification of PSCs provides evidence that bone contains multiple pools of stem cells, each with distinct physiologic functions.}, } @article {pmid30250252, year = {2018}, author = {Huang, Y and Winkler, PA and Sun, W and Lü, W and Du, J}, title = {Architecture of the TRPM2 channel and its activation mechanism by ADP-ribose and calcium.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {145-149}, doi = {10.1038/s41586-018-0558-4}, pmid = {30250252}, issn = {1476-4687}, abstract = {Transient receptor potential melastatin 2 (TRPM2) is a calcium-permeable, non-selective cation channel that has an essential role in diverse physiological processes such as core body temperature regulation, immune response and apoptosis1-4. TRPM2 is polymodal and can be activated by a wide range of stimuli1-7, including temperature, oxidative stress and NAD+-related metabolites such as ADP-ribose (ADPR). Its activation results in both Ca2+ entry across the plasma membrane and Ca2+ release from lysosomes8, and has been linked to diseases such as ischaemia-reperfusion injury, bipolar disorder and Alzheimer's disease9-11. Here we report the cryo-electron microscopy structures of the zebrafish TRPM2 in the apo resting (closed) state and in the ADPR/Ca2+-bound active (open) state, in which the characteristic NUDT9-H domains hang underneath the MHR1/2 domain. We identify an ADPR-binding site located in the bi-lobed structure of the MHR1/2 domain. Our results provide an insight into the mechanism of activation of the TRPM channel family and define a framework for the development of therapeutic agents to treat neurodegenerative diseases and temperature-related pathological conditions.}, } @article {pmid30250251, year = {2018}, author = {Wang, C and Zhang, M and Chen, X and Bertrand, M and Shams-Ansari, A and Chandrasekhar, S and Winzer, P and Lončar, M}, title = {Integrated lithium niobate electro-optic modulators operating at CMOS-compatible voltages.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {101-104}, doi = {10.1038/s41586-018-0551-y}, pmid = {30250251}, issn = {1476-4687}, abstract = {Electro-optic modulators translate high-speed electronic signals into the optical domain and are critical components in modern telecommunication networks1,2 and microwave-photonic systems3,4. They are also expected to be building blocks for emerging applications such as quantum photonics5,6 and non-reciprocal optics7,8. All of these applications require chip-scale electro-optic modulators that operate at voltages compatible with complementary metal-oxide-semiconductor (CMOS) technology, have ultra-high electro-optic bandwidths and feature very low optical losses. Integrated modulator platforms based on materials such as silicon, indium phosphide or polymers have not yet been able to meet these requirements simultaneously because of the intrinsic limitations of the materials used. On the other hand, lithium niobate electro-optic modulators, the workhorse of the optoelectronic industry for decades9, have been challenging to integrate on-chip because of difficulties in microstructuring lithium niobate. The current generation of lithium niobate modulators are bulky, expensive, limited in bandwidth and require high drive voltages, and thus are unable to reach the full potential of the material. Here we overcome these limitations and demonstrate monolithically integrated lithium niobate electro-optic modulators that feature a CMOS-compatible drive voltage, support data rates up to 210 gigabits per second and show an on-chip optical loss of less than 0.5 decibels. We achieve this by engineering the microwave and photonic circuits to achieve high electro-optical efficiencies, ultra-low optical losses and group-velocity matching simultaneously. Our scalable modulator devices could provide cost-effective, low-power and ultra-high-speed solutions for next-generation optical communication networks and microwave photonic systems. Furthermore, our approach could lead to large-scale ultra-low-loss photonic circuits that are reconfigurable on a picosecond timescale, enabling a wide range of quantum and classical applications5,10,11 including feed-forward photonic quantum computation.}, } @article {pmid30250250, year = {2018}, author = {Zhu, F and Farnung, L and Kaasinen, E and Sahu, B and Yin, Y and Wei, B and Dodonova, SO and Nitta, KR and Morgunova, E and Taipale, M and Cramer, P and Taipale, J}, title = {The interaction landscape between transcription factors and the nucleosome.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {76-81}, pmid = {30250250}, issn = {1476-4687}, abstract = {Nucleosomes cover most of the genome and are thought to be displaced by transcription factors in regions that direct gene expression. However, the modes of interaction between transcription factors and nucleosomal DNA remain largely unknown. Here we systematically explore interactions between the nucleosome and 220 transcription factors representing diverse structural families. Consistent with earlier observations, we find that the majority of the studied transcription factors have less access to nucleosomal DNA than to free DNA. The motifs recovered from transcription factors bound to nucleosomal and free DNA are generally similar. However, steric hindrance and scaffolding by the nucleosome result in specific positioning and orientation of the motifs. Many transcription factors preferentially bind close to the end of nucleosomal DNA, or to periodic positions on the solvent-exposed side of the DNA. In addition, several transcription factors usually bind to nucleosomal DNA in a particular orientation. Some transcription factors specifically interact with DNA located at the dyad position at which only one DNA gyre is wound, whereas other transcription factors prefer sites spanning two DNA gyres and bind specifically to each of them. Our work reveals notable differences in the binding of transcription factors to free and nucleosomal DNA, and uncovers a diverse interaction landscape between transcription factors and the nucleosome.}, } @article {pmid30250246, year = {2018}, author = {Leventhal, GE and Boix, C and Kuechler, U and Enke, TN and Sliwerska, E and Holliger, C and Cordero, OX}, title = {Strain-level diversity drives alternative community types in millimetre-scale granular biofilms.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1295-1303}, doi = {10.1038/s41564-018-0242-3}, pmid = {30250246}, issn = {2058-5276}, abstract = {Microbial communities are often highly diverse in their composition, both at a coarse-grained taxonomic level, such as genus, and at a highly resolved level, such as strains, within species. This variability can be driven by either extrinsic factors such as temperature and or by intrinsic ones, for example demographic fluctuations or ecological interactions. The relative contributions of these factors and the taxonomic level at which they influence community composition remain poorly understood, in part because of the difficulty in identifying true community replicates assembled under the same environmental parameters. Here, we address this problem using an activated granular sludge reactor in which millimetre-scale biofilm granules represent true community replicates. Differences in composition are then expected to be driven primarily by biotic factors. Using 142 shotgun metagenomes of single biofilm granules we found that, at the commonly used genus-level resolution, community replicates varied much more in their composition than would be expected from neutral assembly processes. This variation did not translate into any clear partitioning into discrete community types, that is, distinct compositional states, such as enterotypes in the human gut. However, a strong partition into community types did emerge at the strain level for the dominant organism: genotypes of Candidatus Accumulibacter that coexisted in the metacommunity (the reactor) excluded each other within community replicates (granules). Individual granule communities maintained a significant lineage structure, whereby the strain phylogeny of Accumulibacter correlated with the overall composition of the community, indicating a high potential for co-diversification among species and communities. Our results suggest that due to the high functional redundancy and competition between close relatives, alternative community types are most probably observed at the level of recently differentiated genotypes but not at higher orders of genetic resolution.}, } @article {pmid30250245, year = {2018}, author = {Geiger, T and Pazos, M and Lara-Tejero, M and Vollmer, W and Galán, JE}, title = {Peptidoglycan editing by a specific LD-transpeptidase controls the muramidase-dependent secretion of typhoid toxin.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1243-1254}, doi = {10.1038/s41564-018-0248-x}, pmid = {30250245}, issn = {2058-5276}, abstract = {Protein secretion mechanisms are essential for the virulence of most bacterial pathogens. Typhoid toxin is an essential virulence factor for Salmonella Typhi, the cause of typhoid fever in humans. This toxin is unique in that it is only produced within mammalian cells, and it must be trafficked to the extracellular space before intoxicating target cells. An essential and poorly understood aspect of this transport pathway is the secretion of typhoid toxin from the bacterium into the S. Typhi-containing vacuole. We show here that typhoid toxin secretion requires its translocation to the trans side of the peptidoglycan layer at the bacterial poles for subsequent release through the outer membrane. This translocation process depends on a specialized muramidase, the activity of which requires the localized editing of peptidoglycan by a specific ld-transpeptidase. These studies describe a protein export mechanism that is probably conserved in other bacterial species.}, } @article {pmid30250158, year = {2018}, author = {Liedtke, HC and Gower, DJ and Wilkinson, M and Gomez-Mestre, I}, title = {Macroevolutionary shift in the size of amphibian genomes and the role of life history and climate.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1792-1799}, doi = {10.1038/s41559-018-0674-4}, pmid = {30250158}, issn = {2397-334X}, abstract = {The evolution and great diversity of genome size has been of long-standing interest to biologists, but has seldom been investigated on a broad phylogenetic scale. Here we present a comparative quantitative analysis of factors shaping genome size evolution in amphibians, the extant class of vertebrates with the largest variation in genome size. We find that amphibian genomes have undergone saltations in size, although these are rare and the evolutionary history of genome size in amphibians has otherwise been one of gradual, time-dependent variation (that is, Brownian motion). This macroevolutionary homogeneity is remarkable given the evolutionary and ecological diversity of most other aspects of the natural history of amphibians. Contrary to previous claims, we find no evidence for associations between life cycle complexity and genome size despite the high diversity of reproductive modes and the multiple events of independent evolution of divergent life cycles in the group. Climate (temperature and humidity) affects genome size indirectly, at least in frogs, as a consequence of its effect on premetamorphic developmental period, although directionality of the relationship between developmental period and genome size is not unequivocal.}, } @article {pmid30250157, year = {2018}, author = {Li, L and Li, A and Song, K and Meng, J and Guo, X and Li, S and Li, C and De Wit, P and Que, H and Wu, F and Wang, W and Qi, H and Xu, F and Cong, R and Huang, B and Li, Y and Wang, T and Tang, X and Liu, S and Li, B and Shi, R and Liu, Y and Bu, C and Zhang, C and He, W and Zhao, S and Li, H and Zhang, S and Zhang, L and Zhang, G}, title = {Divergence and plasticity shape adaptive potential of the Pacific oyster.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1751-1760}, doi = {10.1038/s41559-018-0668-2}, pmid = {30250157}, issn = {2397-334X}, abstract = {The interplay between divergence and phenotypic plasticity is critical to our understanding of a species' adaptive potential under rapid climate changes. We investigated divergence and plasticity in natural populations of the Pacific oyster Crassostrea gigas with a congeneric oyster Crassostrea angulata from southern China used as an outgroup. Genome re-sequencing of 371 oysters revealed unexpected genetic divergence in a small area that coincided with phenotypic divergence in growth, physiology, heat tolerance and gene expression across environmental gradients. These findings suggest that selection and local adaptation are pervasive and, together with limited gene flow, influence population structure. Genes showing sequence differentiation between populations also diverged in transcriptional response to heat stress. Plasticity in gene expression is positively correlated with evolved divergence, indicating that plasticity is adaptive and favoured by organisms under dynamic environments. Divergence in heat tolerance-partly through acetylation-mediated energy depression-implies differentiation in adaptive potential. Trade-offs between growth and survival may play an important role in local adaptation of oysters and other marine invertebrates.}, } @article {pmid30250156, year = {2018}, author = {Deng, M and Liu, L and Jiang, L and Liu, W and Wang, X and Li, S and Yang, S and Wang, B}, title = {Ecosystem scale trade-off in nitrogen acquisition pathways.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1724-1734}, doi = {10.1038/s41559-018-0677-1}, pmid = {30250156}, issn = {2397-334X}, abstract = {The nitrogen (N) cycle in terrestrial ecosystems is strongly influenced by resorption before litter fall and by mineralization after litter fall. Although both resorption and mineralization make N available to plants and are influenced by climate, their linkage in a changing environment remains largely unknown. Here, our synthesis study shows that, at the global scale, increasing N-resorption efficiency negatively affects the N-mineralization rate. As temperature and precipitation increase, the increasing rates of N cycling closely correspond to a shift from the more conservative resorption pathway to the mineralization pathway. Furthermore, ecosystems with faster N-cycle rates support plant species that have higher foliar N:P ratios and microbial communities with lower fungi:bacteria ratios. Our study shows an ecosystem scale trade-off in N-acquisition pathways. We propose that incorporating the dynamic interaction between N resorption and N mineralization into Earth system models will improve the simulation of nutrient constraints on ecosystem productivity.}, } @article {pmid30250155, year = {2018}, author = {Wolfe, JM and Fournier, GP}, title = {Reply to 'Molecular clocks provide little information to date methanogenic Archaea'.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1678}, doi = {10.1038/s41559-018-0685-1}, pmid = {30250155}, issn = {2397-334X}, } @article {pmid30250154, year = {2018}, author = {Roger, AJ and Susko, E}, title = {Molecular clocks provide little information to date methanogenic Archaea.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1676-1677}, doi = {10.1038/s41559-018-0687-z}, pmid = {30250154}, issn = {2397-334X}, } @article {pmid30250153, year = {2018}, author = {Perkel, JM}, title = {Machine learning gets to grips with plankton challenge.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {567}, doi = {10.1038/d41586-018-06792-5}, pmid = {30250153}, issn = {1476-4687}, } @article {pmid30250152, year = {2018}, author = {AghaKouchak, A and Huning, LS and Chiang, F and Sadegh, M and Vahedifard, F and Mazdiyasni, O and Moftakhari, H and Mallakpour, I}, title = {How do natural hazards cascade to cause disasters?.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {458-460}, doi = {10.1038/d41586-018-06783-6}, pmid = {30250152}, issn = {1476-4687}, } @article {pmid30250151, year = {2018}, author = {Davey Smith, G and Munafò, M and Kivimäki, M}, title = {Swap outdated authorship listings for contributorship credit.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {464}, doi = {10.1038/d41586-018-06815-1}, pmid = {30250151}, issn = {1476-4687}, } @article {pmid30250129, year = {2018}, author = {Yang, J and Ji, C and Liu, D and Wang, X and Zhang, M}, title = {Reply to: 'Organization of the genome sequence of the polyploid crop species Brassica juncea'.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1497-1498}, doi = {10.1038/s41588-018-0240-7}, pmid = {30250129}, issn = {1546-1718}, } @article {pmid30250128, year = {2018}, author = {Wang, M and Li, W and Fang, C and Xu, F and Liu, Y and Wang, Z and Yang, R and Zhang, M and Liu, S and Lu, S and Lin, T and Tang, J and Wang, Y and Wang, H and Lin, H and Zhu, B and Chen, M and Kong, F and Liu, B and Zeng, D and Jackson, SA and Chu, C and Tian, Z}, title = {Parallel selection on a dormancy gene during domestication of crops from multiple families.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1435-1441}, doi = {10.1038/s41588-018-0229-2}, pmid = {30250128}, issn = {1546-1718}, abstract = {Domesticated species often exhibit convergent phenotypic evolution, termed the domestication syndrome, of which loss of seed dormancy is a component. To date, dormancy genes that contribute to parallel domestication across different families have not been reported. Here, we cloned the classical stay-green G gene from soybean and found that it controls seed dormancy and showed evidence of selection during soybean domestication. Moreover, orthologs in rice and tomato also showed evidence of selection during domestication. Analysis of transgenic plants confirmed that orthologs of G had conserved functions in controlling seed dormancy in soybean, rice, and Arabidopsis. Functional investigation demonstrated that G affected seed dormancy through interactions with NCED3 and PSY and in turn modulated abscisic acid synthesis. Therefore, we identified a gene responsible for seed dormancy that has been subject to parallel selection in multiple crop families. This may help facilitate the domestication of new crops.}, } @article {pmid30250127, year = {2018}, author = {Yang, J and Liu, D and Wang, X and Ji, C and Cheng, F and Liu, B and Hu, Z and Chen, S and Pental, D and Ju, Y and Yao, P and Li, X and Xie, K and Zhang, J and Wang, J and Liu, F and Ma, W and Shopan, J and Zheng, H and Mackenzie, SA and Zhang, M}, title = {Author Correction: The genome sequence of allopolyploid Brassica juncea and analysis of differential homoeolog gene expression influencing selection.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1616}, doi = {10.1038/s41588-018-0227-4}, pmid = {30250127}, issn = {1546-1718}, abstract = {Following publication of this article, the authors have corrected 426 chimeric scaffolds in this genome (total scaffold number 10,684). The genome assembly has now been improved as V1.5, and the updated genome assembly is available to be downloaded from http://brassicadb.org/brad/datasets/pub/Genomes/Brassica_juncea/V1.5/ .}, } @article {pmid30250126, year = {2018}, author = {Zhernakova, DV and Le, TH and Kurilshikov, A and Atanasovska, B and Bonder, MJ and Sanna, S and Claringbould, A and Võsa, U and Deelen, P and Franke, L and de Boer, RA and Kuipers, F and Netea, MG and Hofker, MH and Wijmenga, C and Zhernakova, A and Fu, J and , and , }, title = {Individual variations in cardiovascular-disease-related protein levels are driven by genetics and gut microbiome.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1524-1532}, pmid = {30250126}, issn = {1546-1718}, abstract = {Despite a growing body of evidence, the role of the gut microbiome in cardiovascular diseases is still unclear. Here, we present a systems-genome-wide and metagenome-wide association study on plasma concentrations of 92 cardiovascular-disease-related proteins in the population cohort LifeLines-DEEP. We identified genetic components for 73 proteins and microbial associations for 41 proteins, of which 31 were associated to both. The genetic and microbial factors identified mostly exert additive effects and collectively explain up to 76.6% of inter-individual variation (17.5% on average). Genetics contribute most to concentrations of immune-related proteins, while the gut microbiome contributes most to proteins involved in metabolism and intestinal health. We found several host-microbe interactions that impact proteins involved in epithelial function, lipid metabolism, and central nervous system function. This study provides important evidence for a joint genetic and microbial effect in cardiovascular disease and provides directions for future applications in personalized medicine.}, } @article {pmid30250125, year = {2018}, author = {Williams, MJ and Werner, B and Heide, T and Barnes, CP and Graham, TA and Sottoriva, A}, title = {Reply to 'Revisiting signatures of neutral tumor evolution in the light of complexity of cancer genomic data'.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1628-1630}, doi = {10.1038/s41588-018-0210-0}, pmid = {30250125}, issn = {1546-1718}, support = {097319//Wellcome Trust/United Kingdom ; }, } @article {pmid30250124, year = {2018}, author = {He, Z and Bancroft, I}, title = {Organization of the genome sequence of the polyploid crop species Brassica juncea.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1496-1497}, doi = {10.1038/s41588-018-0239-0}, pmid = {30250124}, issn = {1546-1718}, } @article {pmid30250123, year = {2018}, author = {Balaparya, A and De, S}, title = {Revisiting signatures of neutral tumor evolution in the light of complexity of cancer genomic data.}, journal = {Nature genetics}, volume = {50}, number = {12}, pages = {1626-1628}, doi = {10.1038/s41588-018-0219-4}, pmid = {30250123}, issn = {1546-1718}, } @article {pmid30249781, year = {2018}, author = {Lawrence, EA and Kague, E and Aggleton, JA and Harniman, RL and Roddy, KA and Hammond, CL}, title = {The mechanical impact of col11a2 loss on joints; col11a2 mutant zebrafish show changes to joint development and function, which leads to early-onset osteoarthritis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249781}, issn = {1471-2970}, support = {MR/L002566/1//Medical Research Council/United Kingdom ; }, abstract = {Collagen is the major structural component of cartilage, and mutations in the genes encoding type XI collagen are associated with severe skeletal dysplasias (fibrochondrogenesis and Stickler syndrome) and early-onset osteoarthritis (OA). The impact of the lack of type XI collagen on cell behaviour and mechanical performance during skeleton development is unknown. We studied a zebrafish mutant for col11a2 and evaluated cartilage, bone development and mechanical properties to address this. We show that in col11a2 mutants, type II collagen is made but is prematurely degraded in maturing cartilage and ectopically expressed in the joint. These changes are correlated with increased stiffness of both bone and cartilage; quantified using atomic force microscopy. In the mutants, the skeletal rudiment terminal region in the jaw joint is broader and the interzone smaller. These differences in shape and material properties impact on joint function and mechanical performance, which we modelled using finite element analyses. Finally, we show that col11a2 heterozygous carriers reach adulthood but show signs of severe early-onset OA. Taken together, our data demonstrate a key role for type XI collagen in maintaining the properties of cartilage matrix; which when lost leads to alterations to cell behaviour that give rise to joint pathologies.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249780, year = {2018}, author = {Campinho, P and Lamperti, P and Boselli, F and Vermot, J}, title = {Three-dimensional microscopy and image analysis methodology for mapping and quantification of nuclear positions in tissues with approximate cylindrical geometry.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249780}, issn = {1471-2970}, abstract = {Organogenesis involves extensive and dynamic changes of tissue shape during development. It is associated with complex morphogenetic events that require enormous tissue plasticity and generate a large variety of transient three-dimensional geometries that are achieved by global tissue responses. Nevertheless, such global responses are driven by tight spatio-temporal regulation of the behaviours of individual cells composing these tissues. Therefore, the development of image analysis tools that allow for extraction of quantitative data concerning individual cell behaviours is central to study tissue morphogenesis. There are many image analysis tools available that permit extraction of cell parameters. Unfortunately, the majority are developed for tissues with relatively simple geometries such as flat epithelia. Problems arise when the tissue of interest assumes a more complex three-dimensional geometry. Here, we use the endothelium of the developing zebrafish dorsal aorta as an example of a tissue with cylindrical geometry and describe the image analysis routines developed to extract quantitative data on individual cells in such tissues, as well as the image acquisition and sample preparation methodology.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249779, year = {2018}, author = {Courchaine, K and Rugonyi, S}, title = {Quantifying blood flow dynamics during cardiac development: demystifying computational methods.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249779}, issn = {1471-2970}, support = {R01 HL094570/HL/NHLBI NIH HHS/United States ; }, abstract = {Blood flow conditions (haemodynamics) are crucial for proper cardiovascular development. Indeed, blood flow induces biomechanical adaptations and mechanotransduction signalling that influence cardiovascular growth and development during embryonic stages and beyond. Altered blood flow conditions are a hallmark of congenital heart disease, and disrupted blood flow at early embryonic stages is known to lead to congenital heart malformations. In spite of this, many of the mechanisms by which blood flow mechanics affect cardiovascular development remain unknown. This is due in part to the challenges involved in quantifying blood flow dynamics and the forces exerted by blood flow on developing cardiovascular tissues. Recent technologies, however, have allowed precise measurement of blood flow parameters and cardiovascular geometry even at early embryonic stages. Combined with computational fluid dynamics techniques, it is possible to quantify haemodynamic parameters and their changes over development, which is a crucial step in the quest for understanding the role of mechanical cues on heart and vascular formation. This study summarizes some fundamental aspects of modelling blood flow dynamics, with a focus on three-dimensional modelling techniques, and discusses relevant studies that are revealing the details of blood flow and their influence on cardiovascular development.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249778, year = {2018}, author = {Rolfe, RA and Shea, CA and Singh, PNP and Bandyopadhyay, A and Murphy, P}, title = {Investigating the mechanistic basis of biomechanical input controlling skeletal development: exploring the interplay with Wnt signalling at the joint.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249778}, issn = {1471-2970}, abstract = {Embryo movement is essential to the formation of a functional skeleton. Using mouse and chick models, we previously showed that mechanical forces influence gene regulation and tissue patterning, particularly at developing limb joints. However, the molecular mechanisms that underpin the influence of mechanical signals are poorly understood. Wnt signalling is required during skeletal development and is altered under reduced mechanical stimulation. Here, to explore Wnt signalling as a mediator of mechanical input, the expression of Wnt ligand and Fzd receptor genes in the developing skeletal rudiments was profiled. Canonical Wnt activity restricted to the developing joint was shown to be reduced under immobilization, while overexpression of activated β-catenin following electroporation of chick embryo limbs led to joint expansion, supporting the proposed role for Wnt signalling in mechanoresponsive joint patterning. Two key findings advance our understanding of the interplay between Wnt signalling and mechanical stimuli: first, loss of canonical Wnt activity at the joint shows reciprocal, coordinated misregulation of BMP signalling under altered mechanical influence. Second, this occurs simultaneously with increased expression of several Wnt pathway component genes in a territory peripheral to the joint, indicating the importance of mechanical stimulation for a population of potential joint progenitor cells.This article is part of the Theo Murphy meeting issue 'Mechanics of Development'.}, } @article {pmid30249777, year = {2018}, author = {Tetley, RJ and Mao, Y}, title = {The same but different: cell intercalation as a driver of tissue deformation and fluidity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249777}, issn = {1471-2970}, support = {MR/L009056/1//Medical Research Council/United Kingdom ; }, abstract = {The ability of cells to exchange neighbours, termed intercalation, is a key feature of epithelial tissues. Intercalation is predominantly associated with tissue deformations that drive morphogenesis. More recently, however, intercalation that is not associated with large-scale tissue deformations has been described both during animal development and in mature epithelial tissues. This latter form of intercalation appears to contribute to an emerging phenomenon that we refer to as tissue fluidity-the ability of cells to exchange neighbours without changing the overall dimensions of the tissue. Here, we discuss the contribution of junctional dynamics to intercalation governing both morphogenesis and tissue fluidity. In particular, we focus on the relative roles of junctional contractility and cell-cell adhesion as the driving forces behind intercalation. These two contributors to junctional mechanics can be used to simulate cellular intercalation in mechanical computational models, to test how junctional cell behaviours might regulate tissue fluidity and contribute to the maintenance of tissue integrity and the onset of disease.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249776, year = {2018}, author = {Blecher, R and Heinemann-Yerushalmi, L and Assaraf, E and Konstantin, N and Chapman, JR and Cope, TC and Bewick, GS and Banks, RW and Zelzer, E}, title = {New functions for the proprioceptive system in skeletal biology.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249776}, issn = {1471-2970}, abstract = {Muscle spindles and Golgi tendon organs (GTOs) are two types of sensory receptors that respond to changes in length or tension of skeletal muscles. These mechanosensors have long been known to participate in both proprioception and stretch reflex. Here, we present recent findings implicating these organs in maintenance of spine alignment as well as in realignment of fractured bones. These discoveries have been made in several mouse lines lacking functional mechanosensors in part or completely. In both studies, the absence of functional spindles and GTOs produced a more severe phenotype than that of spindles alone. Interestingly, the spinal curve phenotype, which appeared during peripubertal development, bears resemblance to the human condition adolescent idiopathic scoliosis. This similarity may contribute to the study of the disease by offering both an animal model and a clue as to its aetiology. Moreover, it raises the possibility that impaired proprioceptive signalling may be involved in the aetiology of other conditions. Overall, these new findings expand considerably the scope of involvement of proprioception in musculoskeletal development and function.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249775, year = {2018}, author = {Pan, XS and Li, J and Brown, EB and Kuo, CK}, title = {Embryo movements regulate tendon mechanical property development.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249775}, issn = {1471-2970}, abstract = {Tendons transmit forces from muscles to bones to enable skeletal motility. During development, tendons begin to bear load at the onset of embryo movements. Using the chick embryo model, this study showed that altered embryo movement frequency led to changes in elastic modulus of calcaneal tendon. In particular, paralysis led to decreased modulus, whereas hypermotility led to increased modulus. Paralysis also led to reductions in activity levels of lysyl oxidase (LOX), an enzyme that we previously showed is required for cross-linking-mediated elaboration of tendon mechanical properties. Additionally, inhibition of LOX activity abrogated hypermotility-induced increases in modulus. Taken together, our findings suggest embryo movements are critical for tendon mechanical property development and implicate LOX in this process. These exciting findings expand current knowledge of how functional tendons form during development and could guide future clinical approaches to treat tendon defects associated with abnormal mechanical loading in uteroThis article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249774, year = {2018}, author = {Ingber, DE}, title = {From mechanobiology to developmentally inspired engineering.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249774}, issn = {1471-2970}, abstract = {The field of mechanobiology emerged based on the recognition of the central role that physical forces play in development and physiology. In this article, which is based on a lecture I presented at the 2018 Royal Society meeting on Mechanics of Development, I review work from my laboratory carried out over the 40 years which helped to birth this field. I will also describe how we are leveraging the fundamental design principles that govern mechanoregulation to develop new experimental tools and organ-engineering approaches as well as novel mechanotherapeutics.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249773, year = {2018}, author = {Chevalier, NR}, title = {The first digestive movements in the embryo are mediated by mechanosensitive smooth muscle calcium waves.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249773}, issn = {1471-2970}, abstract = {Peristalsis enables transport of the food bolus in the gut. Here, I show by dynamic ex vivo intra-cellular calcium imaging on living embryonic gut explants that the most primitive form of peristalsis that occurs in the embryo is the result of inter-cellular, gap-junction-dependent calcium waves that propagate in the circular smooth muscle layer. I show that the embryonic gut is an intrinsically mechanosensitive organ, as the slightest externally applied mechanical stimulus triggers contractile waves. This dynamic response is an embryonic precursor of the 'law of the intestine' (peristaltic reflex). I show how characteristic features of early peristalsis such as counter-propagating wave annihilation, mechanosensitivity and nucleation after wounding all result from known properties of calcium waves. I finally demonstrate that inter-cellular mechanical tension does not play a role in the propagation mechanism of gut contractile waves, unlike what has been recently shown for the embryonic heartbeat. Calcium waves are a ubiquitous dynamic signalling mechanism in biology: here I show that they are the foundation of digestive movements in the developing embryo.This article is part of the Theo Murphy meeting issue on 'Mechanics of development'.}, } @article {pmid30249772, year = {2018}, author = {Garcia, KE and Kroenke, CD and Bayly, PV}, title = {Mechanics of cortical folding: stress, growth and stability.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249772}, issn = {1471-2970}, abstract = {Cortical folding, or gyrification, coincides with several important developmental processes. The folded shape of the human brain allows the cerebral cortex, the thin outer layer of neurons and their associated projections, to attain a large surface area relative to brain volume. Abnormal cortical folding has been associated with severe neurological, cognitive and behavioural disorders, such as epilepsy, autism and schizophrenia. However, despite decades of study, the mechanical forces that lead to cortical folding remain incompletely understood. Leading hypotheses have focused on the roles of (i) tangential growth of the outer cortex, (ii) spatio-temporal patterns in the birth and migration of neurons, and (iii) internal tension in axons. Recent experimental studies have illuminated not only the fundamental cellular and molecular processes underlying cortical development, but also the stress state, mechanical properties and spatio-temporal patterns of growth in the developing brain. The combination of mathematical modelling and physical measurements has allowed researchers to evaluate hypothesized mechanisms of folding, to determine whether each is consistent with physical laws. This review summarizes what physical scientists have learned from models and recent experimental observations, in the context of recent neurobiological discoveries regarding cortical development. Here, we highlight evidence of a combined mechanism, in which spatio-temporal patterns bias the locations of primary folds (i), but tangential growth of the cortical plate induces mechanical instability (ii) to propagate primary and higher-order folds.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249771, year = {2018}, author = {Norman, J and Sorrell, EL and Hu, Y and Siripurapu, V and Garcia, J and Bagwell, J and Charbonneau, P and Lubkin, SR and Bagnat, M}, title = {Tissue self-organization underlies morphogenesis of the notochord.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249771}, issn = {1471-2970}, support = {F31 GM122422/GM/NIGMS NIH HHS/United States ; R01 AR065439/AR/NIAMS NIH HHS/United States ; }, abstract = {The notochord is a conserved axial structure that in vertebrates serves as a hydrostatic scaffold for embryonic axis elongation and, later on, for proper spine assembly. It consists of a core of large fluid-filled vacuolated cells surrounded by an epithelial sheath that is encased in extracellular matrix. During morphogenesis, the vacuolated cells inflate their vacuole and arrange in a stereotypical staircase pattern. We investigated the origin of this pattern and found that it can be achieved purely by simple physical principles. We are able to model the arrangement of vacuolated cells within the zebrafish notochord using a physical model composed of silicone tubes and water-absorbing polymer beads. The biological structure and the physical model can be accurately described by the theory developed for the packing of spheres and foams in cylinders. Our experiments with physical models and numerical simulations generated several predictions on key features of notochord organization that we documented and tested experimentally in zebrafish. Altogether, our data reveal that the organization of the vertebrate notochord is governed by the density of the osmotically swelling vacuolated cells and the aspect ratio of the notochord rod. We therefore conclude that self-organization underlies morphogenesis of the vertebrate notochord.This article is part of the Theo Murphy meeting issue on 'Mechanics of development'.}, } @article {pmid30249770, year = {2018}, author = {Jaslove, JM and Nelson, CM}, title = {Smooth muscle: a stiff sculptor of epithelial shapes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249770}, issn = {1471-2970}, abstract = {Smooth muscle is increasingly recognized as a key mechanical sculptor of epithelia during embryonic development. Smooth muscle is a mesenchymal tissue that surrounds the epithelia of organs including the gut, blood vessels, lungs, bladder, ureter, uterus, oviduct and epididymis. Smooth muscle is stiffer than its adjacent epithelium and often serves its morphogenetic function by physically constraining the growth of a proliferating epithelial layer. This constraint leads to mechanical instabilities and epithelial morphogenesis through buckling. Smooth muscle stiffness alone, without smooth muscle cell shortening, seems to be sufficient to drive epithelial morphogenesis. Fully understanding the development of organs that use smooth muscle stiffness as a driver of morphogenesis requires investigating how smooth muscle develops, a key aspect of which is distinguishing smooth muscle-like tissues from one another in vivo and in culture. This necessitates a comprehensive appreciation of the genetic, anatomical and functional markers that are used to distinguish the different subtypes of smooth muscle (for example, vascular versus visceral) from similar cell types (including myofibroblasts and myoepithelial cells). Here, we review how smooth muscle acts as a mechanical driver of morphogenesis and discuss ways of identifying smooth muscle, which is critical for understanding these morphogenetic events.This article is part of the Theo Murphy meeting issue 'Mechanics of Development'.}, } @article {pmid30249769, year = {2018}, author = {Parisi, C and Chandaria, VV and Nowlan, NC}, title = {Blocking mechanosensitive ion channels eliminates the effects of applied mechanical loading on chick joint morphogenesis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249769}, issn = {1471-2970}, abstract = {Abnormalities in joint shape are increasingly considered a critical risk factor for developing osteoarthritis in life. It has been shown that mechanical forces during prenatal development, particularly those due to fetal movements, play a fundamental role in joint morphogenesis. However, how mechanical stimuli are sensed or transduced in developing joint tissues is unclear. Stretch-activated and voltage-gated calcium ion channels have been shown to be involved in the mechanoregulation of chondrocytes in vitro In this study, we analyse, for the first time, how blocking these ion channels influences the effects of mechanical loading on chick joint morphogenesis. Using in vitro culture of embryonic chick hindlimb explants in a mechanostimulation bioreactor, we block stretch-activated and voltage-gated ion channels using, respectively, gadolinium chloride and nifedipine. We find that the administration of high doses of either drug largely removed the effects of mechanical stimulation on growth and shape development in vitro, while neither drug had any effect in static cultures. This study demonstrates that, during joint morphogenesis, mechanical cues are transduced-at least in part-through mechanosensitive calcium ion channels, advancing our understanding of cartilage development and mechanotransduction.This article is part of the Theo Murphy meeting issue 'Mechanics of development'.}, } @article {pmid30249768, year = {2018}, author = {Nowlan, NC and Francis-West, P and Nelson, C}, title = {Mechanics of development.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1759}, pages = {}, pmid = {30249768}, issn = {1471-2970}, } @article {pmid30249667, year = {2018}, author = {Arjunan, P and Lin, X and Tang, Z and Du, Y and Kumar, A and Liu, L and Yin, X and Huang, L and Chen, W and Chen, Q and Ye, Z and Wang, S and Kuang, H and Zhou, L and Xu, K and Chen, X and Zeng, H and Lu, W and Cao, Y and Liu, Y and Zhao, C and Li, X}, title = {VEGF-B is a potent antioxidant.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10351-10356}, pmid = {30249667}, issn = {1091-6490}, mesh = {Animals ; Antibodies, Neutralizing/pharmacology ; Antioxidants/*metabolism ; Apoptosis/drug effects/genetics ; Disease Models, Animal ; Gene Expression Regulation ; Glutathione Peroxidase/genetics ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Oxidative Stress ; Retina/drug effects/pathology ; Retinal Degeneration/drug therapy/*genetics ; Retinitis Pigmentosa/genetics ; Vascular Endothelial Growth Factor B/genetics/*metabolism/pharmacology ; Vascular Endothelial Growth Factor Receptor-1/genetics/metabolism ; }, abstract = {VEGF-B was discovered a long time ago. However, unlike VEGF-A, whose function has been extensively studied, the function of VEGF-B and the mechanisms involved still remain poorly understood. Notwithstanding, drugs that inhibit VEGF-B and other VEGF family members have been used to treat patients with neovascular diseases. It is therefore critical to have a better understanding of VEGF-B function and the underlying mechanisms. Here, using comprehensive methods and models, we have identified VEGF-B as a potent antioxidant. Loss of Vegf-b by gene deletion leads to retinal degeneration in mice, and treatment with VEGF-B rescues retinal cells from death in a retinitis pigmentosa model. Mechanistically, we demonstrate that VEGF-B up-regulates numerous key antioxidative genes, particularly, Gpx1 Loss of Gpx1 activity largely diminished the antioxidative effect of VEGF-B, demonstrating that Gpx1 is at least one of the critical downstream effectors of VEGF-B. In addition, we found that the antioxidant function of VEGF-B is mediated mainly by VEGFR1. Given that oxidative stress is a crucial factor in numerous human diseases, VEGF-B may have therapeutic value for the treatment of such diseases.}, } @article {pmid30249666, year = {2018}, author = {Wight, A and Mahmoud, AB and Scur, M and Tu, MM and Rahim, MMA and Sad, S and Makrigiannis, AP}, title = {Critical role for the Ly49 family of class I MHC receptors in adaptive natural killer cell responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {45}, pages = {11579-11584}, pmid = {30249666}, issn = {1091-6490}, support = {MOP 62841//Canadian Institutes of Health Research/International ; }, abstract = {Adaptive natural killer (NK) cell memory represents a new frontier in immunology. Work over the last decade has discovered and confirmed the existence of NK cells with antigen-specific memories, which had previously been considered a unique property of T and B cells. These findings have shown that antigen-specific NK cells gain their specificity without the use of RAG proteins, representing a novel mechanism for generating antigen specificity, but the details of this mechanism have remained a mystery. We have discovered that members of the Ly49 family of surface receptors are critically involved in both the sensitization and the challenge phases of an NK cell memory response, as is antigen presentation from their binding partner, the class I MHC. Moreover, we demonstrate that the Ly49-interacting component of a presented antigen dictates the specificity of the NK cell memory response, implicating Ly49 receptors themselves in antigen-specific recognition. Finally, we demonstrate that adaptive NK cell memories can protect against an otherwise lethal melanoma without T cell or B cell support. These findings offer insight into the mechanism behind NK cell antigen specificity and demonstrate the clinical potential of this adaptive immune cell.}, } @article {pmid30249665, year = {2018}, author = {Kauppila, TES and Bratic, A and Jensen, MB and Baggio, F and Partridge, L and Jasper, H and Grönke, S and Larsson, NG}, title = {Mutations of mitochondrial DNA are not major contributors to aging of fruit flies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9620-E9629}, pmid = {30249665}, issn = {1091-6490}, mesh = {Animals ; *DNA, Mitochondrial/genetics/metabolism ; Drosophila melanogaster ; Longevity/*genetics ; *Mutation ; }, abstract = {Mammals develop age-associated clonal expansion of somatic mtDNA mutations resulting in severe respiratory chain deficiency in a subset of cells in a variety of tissues. Both mathematical modeling based on descriptive data from humans and experimental data from mtDNA mutator mice suggest that the somatic mutations are formed early in life and then undergo mitotic segregation during adult life to reach very high levels in certain cells. To address whether mtDNA mutations have a universal effect on aging metazoans, we investigated their role in physiology and aging of fruit flies. To this end, we utilized genetically engineered flies expressing mutant versions of the catalytic subunit of mitochondrial DNA polymerase (DmPOLγA) as a means to introduce mtDNA mutations. We report here that lifespan and health in fruit flies are remarkably tolerant to mtDNA mutations. Our results show that the short lifespan and wide genetic bottleneck of fruit flies are limiting the extent of clonal expansion of mtDNA mutations both in individuals and between generations. However, an increase of mtDNA mutations to very high levels caused sensitivity to mechanical and starvation stress, intestinal stem cell dysfunction, and reduced lifespan under standard conditions. In addition, the effects of dietary restriction, widely considered beneficial for organismal health, were attenuated in flies with very high levels of mtDNA mutations.}, } @article {pmid30249664, year = {2018}, author = {Yang, Y and Shen, G and Wang, H and Li, H and Zhang, T and Tao, N and Ding, X and Yu, H}, title = {Interferometric plasmonic imaging and detection of single exosomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10275-10280}, pmid = {30249664}, issn = {1091-6490}, mesh = {Adsorption ; Antibodies/chemistry ; Calibration ; Cell Line ; Equipment Design ; *Exosomes/chemistry/metabolism ; Humans ; Image Processing, Computer-Assisted/*methods ; Interferometry/instrumentation/*methods ; Liposomes/analysis/chemistry ; Membrane Fusion ; Microscopy, Fluorescence/methods ; Nanoparticles ; Surface Plasmon Resonance/methods ; Surface Properties ; }, abstract = {Exosomes play an important role in numerous cellular processes. Fundamental study and practical use of exosomes are significantly constrained by the lack of analytical tools capable of physical and biochemical characterization. In this paper, we present an optical approach capable of imaging single exosomes in a label-free manner, using interferometric plasmonic microscopy. We demonstrate monitoring of the real-time adsorption of exosomes onto a chemically modified Au surface, calculating the image intensity, and determining the size distribution. The sizing capability enables us to quantitatively measure the membrane fusion activity between exosomes and liposomes. We also report the recording of the dynamic interaction between exosomes and antibodies at the single-exosome level, and the tracking of hit-stay-run behavior of exosomes on an antibody-coated surface. We anticipate that the proposed method will contribute to clinical exosome analysis and to the exploration of fundamental issues such as the exosome-antibody binding kinetics.}, } @article {pmid30249663, year = {2018}, author = {Asche, F and Garlock, TM and Anderson, JL and Bush, SR and Smith, MD and Anderson, CM and Chu, J and Garrett, KA and Lem, A and Lorenzen, K and Oglend, A and Tveteras, S and Vannuccini, S}, title = {Three pillars of sustainability in fisheries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {44}, pages = {11221-11225}, pmid = {30249663}, issn = {1091-6490}, mesh = {Conservation of Natural Resources/economics ; Ecology/economics ; Ecosystem ; Fisheries/*economics ; Humans ; Seafood/economics ; Socioeconomic Factors ; }, abstract = {Sustainability of global fisheries is a growing concern. The United Nations has identified three pillars of sustainability: economic development, social development, and environmental protection. The fisheries literature suggests that there are two key trade-offs among these pillars of sustainability. First, poor ecological health of a fishery reduces economic profits for fishers, and second, economic profitability of individual fishers undermines the social objectives of fishing communities. Although recent research has shown that management can reconcile ecological and economic objectives, there are lingering concerns about achieving positive social outcomes. We examined trade-offs among the three pillars of sustainability by analyzing the Fishery Performance Indicators, a unique dataset that scores 121 distinct fishery systems worldwide on 68 metrics categorized by social, economic, or ecological outcomes. For each of the 121 fishery systems, we averaged the outcome measures to create overall scores for economic, ecological, and social performance. We analyzed the scores and found that they were positively associated in the full sample. We divided the data into subsamples that correspond to fisheries management systems with three categories of access-open access, access rights, and harvest rights-and performed a similar analysis. Our results show that economic, social, and ecological objectives are at worst independent and are mutually reinforcing in both types of managed fisheries. The implication is that rights-based management systems should not be rejected on the basis of potentially negative social outcomes; instead, social considerations should be addressed in the design of these systems.}, } @article {pmid30249662, year = {2018}, author = {Matsuura, S and Katsumi, H and Suzuki, H and Hirai, N and Hayashi, H and Koshino, K and Higuchi, T and Yagi, Y and Kimura, H and Sakane, T and Yamamoto, A}, title = {l-Serine-modified polyamidoamine dendrimer as a highly potent renal targeting drug carrier.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10511-10516}, pmid = {30249662}, issn = {1091-6490}, mesh = {Angiotensin-Converting Enzyme Inhibitors/administration & dosage/chemistry/pharmacology ; Animals ; Captopril/administration & dosage/chemistry/*pharmacology ; Dendrimers/*administration & dosage/chemistry ; Drug Carriers/*administration & dosage/chemistry ; *Drug Delivery Systems ; Kidney Diseases/*drug therapy ; Mice ; Polyamines/*chemistry ; Serine/*chemistry ; }, abstract = {Effective delivery of drug carriers selectively to the kidney is challenging because of their uptake by the reticuloendothelial system in the liver and spleen, which limits effective treatment of kidney diseases and results in side effects. To address this issue, we synthesized l-serine (Ser)-modified polyamidoamine dendrimer (PAMAM) as a potent renal targeting drug carrier. Approximately 82% of the dose was accumulated in the kidney at 3 h after i.v. injection of 111In-labeled Ser-PAMAM in mice, while i.v. injection of 111In-labeled unmodified PAMAM, l-threonine modified PAMAM, and l-tyrosine modified PAMAM resulted in kidney accumulations of 28%, 35%, and 31%, respectively. Single-photon emission computed tomography/computed tomography (SPECT/CT) images also indicated that 111In-labeled Ser-PAMAM specifically accumulated in the kidneys. An intrakidney distribution study showed that fluorescein isothiocyanate-labeled Ser-PAMAM accumulated predominantly in renal proximal tubules. Results of a cellular uptake study of Ser-PAMAM in LLC-PK1 cells in the presence of inhibitors [genistein, 5-(N-ethyl-N-isopropyl)amiloride, and lysozyme] revealed that caveolae-mediated endocytosis, micropinocytosis, and megalin were associated with the renal accumulation of Ser-PAMAM. The efficient renal distribution and angiotensin-converting enzyme (ACE) inhibition effect of captopril (CAP), an ACE inhibitor, was observed after i.v. injection of the Ser-PAMAM-CAP conjugate. These findings indicate that Ser-PAMAM is a promising renal targeting drug carrier for the treatment of kidney diseases. Thus, the results of this study demonstrate efficient renal targeting of a drug carrier via Ser modification.}, } @article {pmid30249661, year = {2018}, author = {Glustrom, LW and Lyon, KR and Paschini, M and Reyes, CM and Parsonnet, NV and Toro, TB and Lundblad, V and Wuttke, DS}, title = {Single-stranded telomere-binding protein employs a dual rheostat for binding affinity and specificity that drives function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10315-10320}, pmid = {30249661}, issn = {1091-6490}, support = {P30 CA014195/CA/NCI NIH HHS/United States ; R01 GM059414/GM/NIGMS NIH HHS/United States ; R01 GM106060/GM/NIGMS NIH HHS/United States ; T32 GM007240/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; DNA, Single-Stranded/*metabolism ; Mutagenesis, Site-Directed ; Mutation ; Saccharomyces cerevisiae/*genetics/growth & development/physiology ; Saccharomyces cerevisiae Proteins/chemistry/*genetics/*metabolism ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/chemistry/*genetics/*metabolism ; }, abstract = {ssDNA, which is involved in numerous aspects of chromosome biology, is managed by a suite of proteins with tailored activities. The majority of these proteins bind ssDNA indiscriminately, exhibiting little apparent sequence preference. However, there are several notable exceptions, including the Saccharomyces cerevisiae Cdc13 protein, which is vital for yeast telomere maintenance. Cdc13 is one of the tightest known binders of ssDNA and is specific for G-rich telomeric sequences. To investigate how these two different biochemical features, affinity and specificity, contribute to function, we created an unbiased panel of alanine mutations across the Cdc13 DNA-binding interface, including several aromatic amino acids that play critical roles in binding activity. A subset of mutant proteins exhibited significant loss in affinity in vitro that, as expected, conferred a profound loss of viability in vivo. Unexpectedly, a second category of mutant proteins displayed an increase in specificity, manifested as an inability to accommodate changes in ssDNA sequence. Yeast strains with specificity-enhanced mutations displayed a gradient of viability in vivo that paralleled the loss in sequence tolerance in vitro, arguing that binding specificity can be fine-tuned to ensure optimal function. We propose that DNA binding by Cdc13 employs a highly cooperative interface whereby sequence diversity is accommodated through plastic binding modes. This suggests that sequence specificity is not a binary choice but rather is a continuum. Even in proteins that are thought to be specific nucleic acid binders, sequence tolerance through the utilization of multiple binding modes may be a broader phenomenon than previously appreciated.}, } @article {pmid30249660, year = {2018}, author = {Xiao, GY and Mohanakrishnan, A and Schmid, SL}, title = {Role for ERK1/2-dependent activation of FCHSD2 in cancer cell-selective regulation of clathrin-mediated endocytosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9570-E9579}, pmid = {30249660}, issn = {1091-6490}, support = {R01 GM073165/GM/NIGMS NIH HHS/United States ; R01 MH061345/MH/NIMH NIH HHS/United States ; R37 MH061345/MH/NIMH NIH HHS/United States ; }, mesh = {Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/pathology ; Carrier Proteins/*biosynthesis/genetics ; Cell Line, Tumor ; Clathrin/genetics/*pharmacokinetics ; *Endocytosis ; *Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics/*metabolism/pathology ; *MAP Kinase Signaling System ; Membrane Proteins/*biosynthesis/genetics ; Mitogen-Activated Protein Kinase 1/genetics/*metabolism ; Mitogen-Activated Protein Kinase 3/genetics/*metabolism ; Neoplasm Proteins/genetics/*metabolism ; }, abstract = {Clathrin-mediated endocytosis (CME) regulates the uptake of cell-surface receptors as well as their downstream signaling activities. We recently reported that signaling can reciprocally regulate CME in cancer cells and that this crosstalk can contribute to cancer progression. To further explore the nature and extent of the crosstalk between signaling and CME in cancer cell biology, we analyzed a panel of oncogenic signaling kinase inhibitors for their effects on CME across a panel of normal and cancerous cells. Inhibition of several kinases selectively affected CME in cancer cells, including inhibition of ERK1/2, which selectively inhibited CME by decreasing the rate of clathrin-coated pit (CCP) initiation. We identified an ERK1/2 substrate, the FCH/F-BAR and SH3 domain-containing protein FCHSD2, as being essential for the ERK1/2-dependent effects on CME and CCP initiation. Our data suggest that ERK1/2 phosphorylation activates FCHSD2 and regulates EGF receptor (EGFR) endocytic trafficking as well as downstream signaling activities. Loss of FCHSD2 activity in nonsmall cell lung cancer (NSCLC) cells leads to increased cell-surface expression and altered signaling downstream of EGFR, resulting in enhanced cell proliferation and migration. The expression level of FCHSD2 is positively correlated with higher NSCLC patient survival rates, suggesting that FCHSD2 can negatively affect cancer progression. These findings provide insight into the mechanisms and consequences of the reciprocal regulation of signaling and CME in cancer cells.}, } @article {pmid30249659, year = {2018}, author = {Reddy, A and Buckley, MB and Arora, A and Bates, FS and Dorfman, KD and Grason, GM}, title = {Stable Frank-Kasper phases of self-assembled, soft matter spheres.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10233-10238}, pmid = {30249659}, issn = {1091-6490}, abstract = {Single molecular species can self-assemble into Frank-Kasper (FK) phases, finite approximants of dodecagonal quasicrystals, defying intuitive notions that thermodynamic ground states are maximally symmetric. FK phases are speculated to emerge as the minimal-distortional packings of space-filling spherical domains, but a precise measure of this distortion and how it affects assembly thermodynamics remains ambiguous. We use two complementary approaches to demonstrate that the principles driving FK lattice formation in diblock copolymers emerge directly from the strong-stretching theory of spherical domains, in which a minimal interblock area competes with a minimal stretching of space-filling chains. The relative stability of FK lattices is studied first using a diblock foam model with unconstrained particle volumes and shapes, which correctly predicts not only the equilibrium σ lattice but also the unequal volumes of the equilibrium domains. We then provide a molecular interpretation for these results via self-consistent field theory, illuminating how molecular stiffness increases the sensitivity of the intradomain chain configurations and the asymmetry of local domain packing. These findings shed light on the role of volume exchange on the formation of distinct FK phases in copolymers and suggest a paradigm for formation of FK phases in soft matter systems in which unequal domain volumes are selected by the thermodynamic competition between distinct measures of shape asymmetry.}, } @article {pmid30249658, year = {2018}, author = {Vos de Wael, R and Larivière, S and Caldairou, B and Hong, SJ and Margulies, DS and Jefferies, E and Bernasconi, A and Smallwood, J and Bernasconi, N and Bernhardt, BC}, title = {Anatomical and microstructural determinants of hippocampal subfield functional connectome embedding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10154-10159}, pmid = {30249658}, issn = {1091-6490}, support = {U54 MH091657/MH/NIMH NIH HHS/United States ; FDN-154298//Canadian Institutes of Health Research/International ; }, mesh = {Adult ; *Connectome ; Female ; Hippocampus/*diagnostic imaging/*physiology ; Humans ; *Magnetic Resonance Imaging ; Male ; Myelin Sheath/metabolism ; }, abstract = {The hippocampus plays key roles in cognition and affect and serves as a model system for structure/function studies in animals. So far, its complex anatomy has challenged investigations targeting its substructural organization in humans. State-of-the-art MRI offers the resolution and versatility to identify hippocampal subfields, assess its microstructure, and study topographical principles of its connectivity in vivo. We developed an approach to unfold the human hippocampus and examine spatial variations of intrinsic functional connectivity in a large cohort of healthy adults. In addition to mapping common and unique connections across subfields, we identified two main axes of subregional connectivity transitions. An anterior/posterior gradient followed long-axis landmarks and metaanalytical findings from task-based functional MRI, while a medial/lateral gradient followed hippocampal infolding and correlated with proxies of cortical myelin. Findings were consistent in an independent sample and highly stable across resting-state scans. Our results provide robust evidence for long-axis specialization in the resting human hippocampus and suggest an intriguing interplay between connectivity and microstructure.}, } @article {pmid30249657, year = {2018}, author = {Deng, J and Wang, P and Chen, X and Cheng, H and Liu, J and Fushimi, K and Zhu, L and Wu, JY}, title = {FUS interacts with ATP synthase beta subunit and induces mitochondrial unfolded protein response in cellular and animal models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9678-E9686}, pmid = {30249657}, issn = {1091-6490}, support = {R01 AG054008/AG/NIA NIH HHS/United States ; R01 CA175360/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Drosophila Proteins/genetics/*metabolism ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/genetics/*metabolism ; Mitochondria/*metabolism/pathology ; Mitochondrial Proton-Translocating ATPases/genetics/*metabolism ; Neurodegenerative Diseases/genetics/*metabolism/pathology ; *Unfolded Protein Response ; }, abstract = {FUS (fused in sarcoma) proteinopathy is a group of neurodegenerative diseases characterized by the formation of inclusion bodies containing the FUS protein, including frontotemporal lobar degeneration and amyotrophic lateral sclerosis. Previous studies show that mitochondrial damage is an important aspect of FUS proteinopathy. However, the molecular mechanisms by which FUS induces mitochondrial damage remain to be elucidated. Our biochemical and genetic experiments demonstrate that FUS interacts with the catalytic subunit of mitochondrial ATP synthase (ATP5B), disrupts the formation of ATP synthase complexes, and inhibits mitochondrial ATP synthesis. FUS expression activates the mitochondrial unfolded protein response (UPRmt). Importantly, down-regulating expression of ATP5B or UPRmt genes in FUS transgenic flies ameliorates neurodegenerative phenotypes. Our data show that mitochondrial impairment is a critical early event in FUS proteinopathy, and provide insights into the pathogenic mechanism of FUS-induced neurodegeneration.}, } @article {pmid30249656, year = {2018}, author = {Huber, R and Knaden, M}, title = {Desert ants possess distinct memories for food and nest odors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10470-10474}, pmid = {30249656}, issn = {1091-6490}, mesh = {Animals ; Ants ; Choice Behavior/*physiology ; Feeding Behavior/*physiology ; Food Preferences/*physiology ; Memory/*physiology ; Nesting Behavior/*physiology ; }, abstract = {The desert ant Cataglyphis fortis inhabits the North African saltpans where it individually forages for dead arthropods. Homing ants rely mainly on path integration, i.e., the processing of directional information from a skylight compass and distance information from an odometer. Due to the far-reaching foraging runs, path integration is error-prone and guides the ants only to the vicinity of the nest, where the ants then use learned visual and olfactory cues to locate the inconspicuous nest entrance. The learning of odors associated with the nest entrance is well established. We furthermore know that foraging Cataglyphis use the food-derived necromone linoleic acid to pinpoint dead insects. Here we show that Cataglyphis in addition can learn the association of a given odor with food. After experiencing food crumbs that were spiked with an innately neutral odor, ants were strongly attracted by the same odor during their next foraging journey. We therefore explored the characteristics of the ants' food-odor memory and identified pronounced differences from their memory for nest-associated odors. Nest odors are learned only after repeated learning trials and become ignored as soon as the ants do not experience them at the nest anymore. In contrast, ants learn food odors after a single experience, remember at least 14 consecutively learned food odors, and do so for the rest of their lives. As an ant experiences many food items during its lifetime, but only a single nest, differentially organized memories for both contexts might be adaptive.}, } @article {pmid30249655, year = {2018}, author = {Karamitros, T and Hurst, T and Marchi, E and Karamichali, E and Georgopoulou, U and Mentis, A and Riepsaame, J and Lin, A and Paraskevis, D and Hatzakis, A and McLauchlan, J and Katzourakis, A and Magiorkinis, G}, title = {Human Endogenous Retrovirus-K HML-2 integration within RASGRF2 is associated with intravenous drug abuse and modulates transcription in a cell-line model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10434-10439}, pmid = {30249655}, issn = {1091-6490}, support = {MR/K010565/1//Medical Research Council/United Kingdom ; MC_UU_12014/1//Medical Research Council/United Kingdom ; }, mesh = {Case-Control Studies ; Child ; Cohort Studies ; Embryonal Carcinoma Stem Cells/*metabolism/pathology ; Endogenous Retroviruses/*genetics ; Female ; Genome, Human ; Humans ; Male ; Substance Abuse, Intravenous/*genetics ; *Transcription, Genetic ; Tumor Cells, Cultured ; Virus Integration/*genetics ; ras Guanine Nucleotide Exchange Factors/*genetics ; }, abstract = {HERV-K HML-2 (HK2) has been proliferating in the germ line of humans at least as recently as 250,000 years ago, with some integrations that remain polymorphic in the modern human population. One of the solitary HK2 LTR polymorphic integrations lies between exons 17 and 18 of RASGRF2, a gene that affects dopaminergic activity and is thus related to addiction. Here we show that this antisense HK2 integration (namely RASGRF2-int) is found more frequently in persons who inject drugs compared with the general population. In a Greek HIV-1-positive population (n = 202), we found RASGRF2-int 2.5 times (14 versus 6%) more frequently in patients infected through i.v. drug use compared with other transmission route controls (P = 0.03). Independently, in a United Kingdom-based hepatitis C virus-positive population (n = 184), we found RASGRF2-int 3.6 times (34 versus 9.5%) more frequently in patients infected during chronic drug abuse compared with controls (P < 0.001). We then tested whether RASGRF2-int could be mechanistically responsible for this association by modulating transcription of RASGRF2 We show that the CRISPR/Cas9-mediated insertion of HK2 in HEK293 cells in the exact RASGRF2 intronic position found in the population resulted in significant transcriptional and phenotypic changes. We also explored mechanistic features of other intronic HK2 integrations and show that HK2 LTRs can be responsible for generation of cis-natural antisense transcripts, which could interfere with the transcription of nearby genes. Our findings suggest that RASGRF2-int is a strong candidate for dopaminergic manipulation, and emphasize the importance of accurate mapping of neglected HERV polymorphisms in human genomic studies.}, } @article {pmid30249654, year = {2018}, author = {Kiss, B and Lee, EJ and Ma, W and Li, FW and Tonino, P and Mijailovich, SM and Irving, TC and Granzier, HL}, title = {Nebulin stiffens the thin filament and augments cross-bridge interaction in skeletal muscle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10369-10374}, pmid = {30249654}, issn = {1091-6490}, support = {P41 GM103622/GM/NIGMS NIH HHS/United States ; R01 AR053897/AR/NIAMS NIH HHS/United States ; R01 AR073179/AR/NIAMS NIH HHS/United States ; S10 OD018090/OD/NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/*metabolism ; Animals ; Cells, Cultured ; Mice ; Mice, Knockout ; Muscle Proteins/*physiology ; Muscle Weakness ; Muscle, Skeletal/cytology/*metabolism ; Myosins/*metabolism ; Tropomyosin/*metabolism ; Troponin/*metabolism ; }, abstract = {Nebulin is a giant sarcomeric protein that spans along the actin filament in skeletal muscle, from the Z-disk to near the thin filament pointed end. Mutations in nebulin cause muscle weakness in nemaline myopathy patients, suggesting that nebulin plays important roles in force generation, yet little is known about nebulin's influence on thin filament structure and function. Here, we used small-angle X-ray diffraction and compared intact muscle deficient in nebulin (using a conditional nebulin-knockout, Neb cKO) with control (Ctrl) muscle. When muscles were activated, the spacing of the actin subunit repeat (27 Å) increased in both genotypes; when converted to thin filament stiffness, the obtained value was 30 pN/nm in Ctrl muscle and 10 pN/nm in Neb cKO muscle; that is, the thin filament was approximately threefold stiffer when nebulin was present. In contrast, the thick filament stiffness was not different between the genotypes. A significantly shorter left-handed (59 Å) thin filament helical pitch was found in passive and contracting Neb cKO muscles, as well as impaired tropomyosin and troponin movement. Additionally, a reduced myosin mass transfer toward the thin filament in contracting Neb cKO muscle was found, suggesting reduced cross-bridge interaction. We conclude that nebulin is critically important for physiological force levels, as it greatly stiffens the skeletal muscle thin filament and contributes to thin filament activation and cross-bridge recruitment.}, } @article {pmid30249653, year = {2018}, author = {Robinson, TR and Rosser, NJ and Densmore, AL and Oven, KJ and Shrestha, SN and Guragain, R}, title = {Use of scenario ensembles for deriving seismic risk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9532-E9541}, pmid = {30249653}, issn = {1091-6490}, abstract = {High death tolls from recent earthquakes show that seismic risk remains high globally. While there has been much focus on seismic hazard, large uncertainties associated with exposure and vulnerability have led to more limited analyses of the potential impacts of future earthquakes. We argue that as both exposure and vulnerability are reducible factors of risk, assessing their importance and variability allows for prioritization of the most effective disaster risk-reduction (DRR) actions. We address this through earthquake ensemble modeling, using the example of Nepal. We model fatalities from 90 different scenario earthquakes and establish whether impacts are specific to certain scenario earthquakes or occur irrespective of the scenario. Our results show that for most districts in Nepal impacts are not specific to the particular characteristics of a single earthquake, and that total modeled impacts are skewed toward the minimum estimate. These results suggest that planning for the worst-case scenario in Nepal may place an unnecessarily large burden on the limited resources available for DRR. We also show that the most at-risk districts are predominantly in rural western Nepal, with ∼9.5 million Nepalis inhabiting districts with higher seismic risk than Kathmandu. Our proposed approach provides a holistic consideration of seismic risk for informing contingency planning and allows the relative importance of the reducible components of risk (exposure and vulnerability) to be estimated, highlighting factors that can be targeted most effectively. We propose this approach for informing contingency planning, especially in locations where information on the likelihood of future earthquakes is inadequate.}, } @article {pmid30249652, year = {2018}, author = {Azar, B}, title = {QnAs with Sang Yup Lee.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9816-9817}, pmid = {30249652}, issn = {1091-6490}, mesh = {History, 21st Century ; Humans ; Metabolic Engineering/*history ; Portraits as Topic ; Republic of Korea ; }, } @article {pmid30249651, year = {2018}, author = {Suwabe, K and Byun, K and Hyodo, K and Reagh, ZM and Roberts, JM and Matsushita, A and Saotome, K and Ochi, G and Fukuie, T and Suzuki, K and Sankai, Y and Yassa, MA and Soya, H}, title = {Rapid stimulation of human dentate gyrus function with acute mild exercise.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10487-10492}, pmid = {30249651}, issn = {1091-6490}, support = {P50 AG016573/AG/NIA NIH HHS/United States ; R01 AG053555/AG/NIA NIH HHS/United States ; R01 MH102392/MH/NIMH NIH HHS/United States ; R21 AG049220/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; CA1 Region, Hippocampal/*physiology ; CA3 Region, Hippocampal/*physiology ; Dentate Gyrus/*physiology ; Exercise/*physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Memory/*physiology ; Neuropsychological Tests ; Young Adult ; }, abstract = {Physical exercise has beneficial effects on neurocognitive function, including hippocampus-dependent episodic memory. Exercise intensity level can be assessed according to whether it induces a stress response; the most effective exercise for improving hippocampal function remains unclear. Our prior work using a special treadmill running model in animals has shown that stress-free mild exercise increases hippocampal neuronal activity and promotes adult neurogenesis in the dentate gyrus (DG) of the hippocampus, improving spatial memory performance. However, the rapid modification, from mild exercise, on hippocampal memory function and the exact mechanisms for these changes, in particular the impact on pattern separation acting in the DG and CA3 regions, are yet to be elucidated. To this end, we adopted an acute-exercise design in humans, coupled with high-resolution functional MRI techniques, capable of resolving hippocampal subfields. A single 10-min bout of very light-intensity exercise (30%[Formula: see text]) results in rapid enhancement in pattern separation and an increase in functional connectivity between hippocampal DG/CA3 and cortical regions (i.e., parahippocampal, angular, and fusiform gyri). Importantly, the magnitude of the enhanced functional connectivity predicted the extent of memory improvement at an individual subject level. These results suggest that brief, very light exercise rapidly enhances hippocampal memory function, possibly by increasing DG/CA3-neocortical functional connectivity.}, } @article {pmid30249650, year = {2018}, author = {}, title = {Correction for Sargent et al., Anthropogenic and biogenic CO2 fluxes in the Boston urban region.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9507}, doi = {10.1073/pnas.1815348115}, pmid = {30249650}, issn = {1091-6490}, } @article {pmid30249649, year = {2018}, author = {Bai, J and Francisco, JS and Zeng, XC}, title = {Two-dimensional dry ices with rich polymorphic and polyamorphic phase behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10263-10268}, pmid = {30249649}, issn = {1091-6490}, abstract = {Both carbon dioxide (CO2) and water (H2O) are triatomic molecules that are ubiquitous in nature, and both are among the five most abundant gases in the Earth's atmosphere. At low temperature and ambient pressure, both CO2 and H2O form molecular crystals--dry ice I and ice I h Because water possesses distinctive hydrogen bonds, it exhibits intricate and highly pressure-dependent phase behavior, including at least 17 crystalline ice phases and three amorphous ice phases. In contrast, due to its weak van der Waals intermolecular interactions, CO2 exhibits fewer crystalline phases except at extremely high pressures, where nonmolecular ordered structures arise. Herein, we show the molecular dynamics simulation results of numerous 2D polymorphs of CO2 molecules in slit nanopores. Unlike bulk polymorphs of CO2, 2D CO2 polymorphs exhibit myriad crystalline and amorphous structures, showing remarkable polymorphism and polyamorphism. We also show that depending on the thermodynamic path, 2D solid-to-solid phase transitions can give rise to previously unreported structures, e.g., wave-like amorphous CO2 structures. Our simulation also suggests intriguing structural connections between 2D and 3D dry ice phases (e.g., Cmca and PA-3) and offers insights into CO2 polyamorphic transitions through intermediate liquid or amorphous phases.}, } @article {pmid30249648, year = {2018}, author = {Trail, D and Boehnke, P and Savage, PS and Liu, MC and Miller, ML and Bindeman, I}, title = {Origin and significance of Si and O isotope heterogeneities in Phanerozoic, Archean, and Hadean zircon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10287-10292}, pmid = {30249648}, issn = {1091-6490}, mesh = {Australia ; Geologic Sediments/chemistry ; Isotopes/*analysis ; Mass Spectrometry/*methods ; Oxygen Isotopes/*analysis ; Silicates/*analysis/*chemistry ; Silicon/*analysis ; South Africa ; Zirconium/*analysis/*chemistry ; }, abstract = {Hydrosphere interactions and alteration of the terrestrial crust likely played a critical role in shaping Earth's surface, and in promoting prebiotic reactions leading to life, before 4.03 Ga (the Hadean Eon). The identity of aqueously altered material strongly depends on lithospheric cycling of abundant and water-soluble elements such as Si and O. However, direct constraints that define the character of Hadean sedimentary material are absent because samples from this earliest eon are limited to detrital zircons (ZrSiO4). Here we show that concurrent measurements of Si and O isotope ratios in Phanerozoic and detrital pre-3.0 Ga zircon constrain the composition of aqueously altered precursors incorporated into their source melts. Phanerozoic zircon from (S)edimentary-type rocks contain heterogeneous δ18O and δ30Si values consistent with assimilation of metapelitic material, distinct from the isotopic character of zircon from (I)gneous- and (A)norogenic-type rocks. The δ18O values of detrital Archean zircons are heterogeneous, although yield Si isotope compositions like mantle-derived zircon. Hadean crystals yield elevated δ18O values (vs. mantle zircon) and δ30Si values span almost the entire range observed for Phanerozoic samples. Coupled Si and O isotope data represent a constraint on Hadean weathering and sedimentary input into felsic melts including remelting of amphibolites possibly of basaltic origin, and fractional addition of chemical sediments, such as cherts and/or banded iron formations (BIFs) into source melts. That such sedimentary deposits were extensive enough to change the chemical signature of intracrustal melts suggests they may have been a suitable niche for (pre)biotic chemistry as early as 4.1 Ga.}, } @article {pmid30249647, year = {2018}, author = {Plantamura, E and Dzutsev, A and Chamaillard, M and Djebali, S and Moudombi, L and Boucinha, L and Grau, M and Macari, C and Bauché, D and Dumitrescu, O and Rasigade, JP and Lippens, S and Plateroti, M and Kress, E and Cesaro, A and Bondu, C and Rothermel, U and Heikenwälder, M and Lina, G and Bentaher-Belaaouaj, A and Marie, JC and Caux, C and Trinchieri, G and Marvel, J and Michallet, MC}, title = {MAVS deficiency induces gut dysbiotic microbiota conferring a proallergic phenotype.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10404-10409}, pmid = {30249647}, issn = {1091-6490}, mesh = {Adaptor Proteins, Signal Transducing/*physiology ; Animals ; Disease Models, Animal ; Dysbiosis/*complications ; Female ; Gastrointestinal Microbiome/*immunology ; Homeodomain Proteins/genetics/metabolism ; Hypersensitivity/*etiology/metabolism/pathology ; Intestines/*immunology/microbiology/pathology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenotype ; Signal Transduction ; Skin Diseases, Bacterial/*etiology/metabolism/pathology ; }, abstract = {Prominent changes in the gut microbiota (referred to as "dysbiosis") play a key role in the development of allergic disorders, but the underlying mechanisms remain unknown. Study of the delayed-type hypersensitivity (DTH) response in mice contributed to our knowledge of the pathophysiology of human allergic contact dermatitis. Here we report a negative regulatory role of the RIG-I-like receptor adaptor mitochondrial antiviral signaling (MAVS) on DTH by modulating gut bacterial ecology. Cohousing and fecal transplantation experiments revealed that the dysbiotic microbiota of Mavs-/- mice conferred a proallergic phenotype that is communicable to wild-type mice. DTH sensitization coincided with increased intestinal permeability and bacterial translocation within lymphoid organs that enhanced DTH severity. Collectively, we unveiled an unexpected impact of RIG-I-like signaling on the gut microbiota with consequences on allergic skin disease outcome. Primarily, these data indicate that manipulating the gut microbiota may help in the development of therapeutic strategies for the treatment of human allergic skin pathologies.}, } @article {pmid30249646, year = {2018}, author = {Pujols, J and Peña-Díaz, S and Lázaro, DF and Peccati, F and Pinheiro, F and González, D and Carija, A and Navarro, S and Conde-Giménez, M and García, J and Guardiola, S and Giralt, E and Salvatella, X and Sancho, J and Sodupe, M and Outeiro, TF and Dalfó, E and Ventura, S}, title = {Small molecule inhibits α-synuclein aggregation, disrupts amyloid fibrils, and prevents degeneration of dopaminergic neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10481-10486}, pmid = {30249646}, issn = {1091-6490}, mesh = {Amyloid/*drug effects/metabolism ; Animals ; Caenorhabditis elegans/*drug effects/metabolism ; Dopaminergic Neurons/*drug effects/metabolism/pathology ; High-Throughput Screening Assays ; Humans ; Neuroblastoma/drug therapy/metabolism/pathology ; Parkinson Disease/*drug therapy/metabolism/pathology ; Protein Aggregation, Pathological/*drug therapy/metabolism/pathology ; Small Molecule Libraries/*pharmacology ; Tumor Cells, Cultured ; alpha-Synuclein/*antagonists & inhibitors/metabolism ; }, abstract = {Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons, a process that current therapeutic approaches cannot prevent. In PD, the typical pathological hallmark is the accumulation of intracellular protein inclusions, known as Lewy bodies and Lewy neurites, which are mainly composed of α-synuclein. Here, we exploited a high-throughput screening methodology to identify a small molecule (SynuClean-D) able to inhibit α-synuclein aggregation. SynuClean-D significantly reduces the in vitro aggregation of wild-type α-synuclein and the familiar A30P and H50Q variants in a substoichiometric molar ratio. This compound prevents fibril propagation in protein-misfolding cyclic amplification assays and decreases the number of α-synuclein inclusions in human neuroglioma cells. Computational analysis suggests that SynuClean-D can bind to cavities in mature α-synuclein fibrils and, indeed, it displays a strong fibril disaggregation activity. The treatment with SynuClean-D of two PD Caenorhabditis elegans models, expressing α-synuclein either in muscle or in dopaminergic neurons, significantly reduces the toxicity exerted by α-synuclein. SynuClean-D-treated worms show decreased α-synuclein aggregation in muscle and a concomitant motility recovery. More importantly, this compound is able to rescue dopaminergic neurons from α-synuclein-induced degeneration. Overall, SynuClean-D appears to be a promising molecule for therapeutic intervention in Parkinson's disease.}, } @article {pmid30249645, year = {2018}, author = {Viegas, J}, title = {Profile of Jonathan D. G. Jones.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10191-10194}, pmid = {30249645}, issn = {1091-6490}, mesh = {DNA Transposable Elements ; Disease Resistance/genetics ; Gene Editing ; History, 20th Century ; History, 21st Century ; Host-Pathogen Interactions/*genetics ; Plant Immunity ; Plant Proteins/genetics/immunology ; Plants/*genetics/immunology/microbiology ; Plants, Genetically Modified ; }, } @article {pmid30249644, year = {2018}, author = {Kholodar, SA and Ghosh, AK and Świderek, K and Moliner, V and Kohen, A}, title = {Parallel reaction pathways and noncovalent intermediates in thymidylate synthase revealed by experimental and computational tools.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10311-10314}, pmid = {30249644}, issn = {1091-6490}, support = {R01 GM065368/GM/NIGMS NIH HHS/United States ; }, mesh = {Catalysis ; Deoxyuracil Nucleotides/chemistry/metabolism ; Escherichia coli Proteins/chemistry/metabolism ; Kinetics ; Molecular Dynamics Simulation ; Quantum Theory ; Tetrahydrofolates/chemistry/metabolism ; Thymidylate Synthase/*chemistry/*metabolism ; }, abstract = {Thymidylate synthase was one of the most studied enzymes due to its critical role in molecular pathogenesis of cancer. Nevertheless, many atomistic details of its chemical mechanism remain unknown or debated, thereby imposing limits on design of novel mechanism-based anticancer therapeutics. Here, we report unprecedented isolation and characterization of a previously proposed intact noncovalent bisubstrate intermediate formed in the reaction catalyzed by thymidylate synthase. Free-energy surfaces of the bisubstrate intermediates interconversions computed with quantum mechanics/molecular mechanics (QM/MM) methods and experimental assessment of the corresponding kinetics indicate that the species is the most abundant productive intermediate along the reaction coordinate, whereas accumulation of the covalent bisubstrate species largely occurs in a parallel nonproductive pathway. Our findings not only substantiate relevance of the previously proposed noncovalent intermediate but also support potential implications of the overstabilized covalent intermediate in drug design targeting DNA biosynthesis.}, } @article {pmid30249643, year = {2018}, author = {Xu, L and Kong, L and Wang, J and Ash, JD}, title = {Stimulation of AMPK prevents degeneration of photoreceptors and the retinal pigment epithelium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10475-10480}, pmid = {30249643}, issn = {1091-6490}, support = {R01 EY016459/EY/NEI NIH HHS/United States ; }, mesh = {AMP-Activated Protein Kinases/*physiology ; Animals ; *Disease Models, Animal ; Female ; Hypoglycemic Agents/pharmacology ; Male ; Metformin/*pharmacology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/drug effects ; Oxidative Stress/drug effects ; Photoreceptor Cells/*drug effects/metabolism ; Retinal Degeneration/metabolism/pathology/*prevention & control ; Retinal Pigment Epithelium/*drug effects/metabolism ; }, abstract = {Retinal degenerative diseases are generally characterized by a permanent loss of light-sensitive retinal neurons known as photoreceptors, or their support cells, the retinal pigmented epithelium (RPE). Metabolic dysfunction has been implicated as a common mechanism of degeneration. In this study, we used the drug metformin in a gain-of-function approach to activate adenosine monophosphate-activated protein kinase (AMPK). We found that treatment protected photoreceptors and the RPE from acute injury and delayed inherited retinal degeneration. Protection was associated with decreased oxidative stress, decreased DNA damage, and increased mitochondrial energy production. To determine whether protection was a local or a systemic effect of metformin, we used AMPK retinal knockout mice and found that local expression of AMPK catalytic subunit α2 was required for metformin-induced protection. Our data demonstrate that increasing the activity of AMPK in retinal neurons or glia can delay or prevent degeneration of photoreceptors and the RPE from multiple types of cell-death triggers.}, } @article {pmid30249642, year = {2018}, author = {Garcia, MD and Chua, SMH and Low, YS and Lee, YT and Agnew-Francis, K and Wang, JG and Nouwens, A and Lonhienne, T and Williams, CM and Fraser, JA and Guddat, LW}, title = {Commercial AHAS-inhibiting herbicides are promising drug leads for the treatment of human fungal pathogenic infections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9649-E9658}, pmid = {30249642}, issn = {1091-6490}, mesh = {*Acetolactate Synthase/antagonists & inhibitors/chemistry/metabolism ; Animals ; *Antifungal Agents/chemistry/pharmacology ; Candida albicans/*enzymology ; *Candidiasis/drug therapy/enzymology ; *Cryptococcosis/drug therapy/enzymology ; Cryptococcus neoformans/*enzymology ; *Fungal Proteins/antagonists & inhibitors/chemistry ; Herbicides/chemistry/pharmacology ; Humans ; Mice ; }, abstract = {The increased prevalence of drug-resistant human pathogenic fungal diseases poses a major threat to global human health. Thus, new drugs are urgently required to combat these infections. Here, we demonstrate that acetohydroxyacid synthase (AHAS), the first enzyme in the branched-chain amino acid biosynthesis pathway, is a promising new target for antifungal drug discovery. First, we show that several AHAS inhibitors developed as commercial herbicides are powerful accumulative inhibitors of Candida albicans AHAS (Ki values as low as 800 pM) and have determined high-resolution crystal structures of this enzyme in complex with several of these herbicides. In addition, we have demonstrated that chlorimuron ethyl (CE), a member of the sulfonylurea herbicide family, has potent antifungal activity against five different Candida species and Cryptococcus neoformans (with minimum inhibitory concentration, 50% values as low as 7 nM). Furthermore, in these assays, we have shown CE and itraconazole (a P450 inhibitor) can act synergistically to further improve potency. Finally, we show in Candida albicans-infected mice that CE is highly effective in clearing pathogenic fungal burden in the lungs, liver, and spleen, thus reducing overall mortality rates. Therefore, in view of their low toxicity to human cells, AHAS inhibitors represent a new class of antifungal drug candidates.}, } @article {pmid30249641, year = {2018}, author = {Peteet, DM and Nichols, J and Kenna, T and Chang, C and Browne, J and Reza, M and Kovari, S and Liberman, L and Stern-Protz, S}, title = {Sediment starvation destroys New York City marshes' resistance to sea level rise.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10281-10286}, pmid = {30249641}, issn = {1091-6490}, mesh = {Agriculture ; Bays ; Conservation of Natural Resources ; Estuaries ; Geologic Sediments/*analysis ; Isotopes/analysis ; Lead/analysis ; New York City ; *Wetlands ; }, abstract = {New York City (NYC) is representative of many vulnerable coastal urban populations, infrastructures, and economies threatened by global sea level rise. The steady loss of marshes in NYC's Jamaica Bay is typical of many urban estuaries worldwide. Essential to the restoration and preservation of these key wetlands is an understanding of their sedimentation. Here we present a reconstruction of the history of mineral and organic sediment fluxes in Jamaica Bay marshes over three centuries, using a combination of density measurements and a detailed accretion model. Accretion rate is calculated using historical land use and pollution markers, through a wide variety of sediment core analyses including geochemical, isotopic, and paleobotanical analyses. We find that, since 1800 CE, urban development dramatically reduced the input of marsh-stabilizing mineral sediment. However, as mineral flux decreased, organic matter flux increased. While this organic accumulation increase allowed vertical accumulation to outpace sea level, reduced mineral content causes structural weakness and edge failure. Marsh integrity now requires mineral sediment addition to both marshes and subsurface channels and borrow pits, a solution applicable to drowning estuaries worldwide. Integration of marsh mineral/organic accretion history with modeling provides parameters for marsh preservation at specific locales with sea level rise.}, } @article {pmid30249640, year = {2018}, author = {}, title = {Correction for Taylor et al., Origins of equine dentistry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9508}, doi = {10.1073/pnas.1815049115}, pmid = {30249640}, issn = {1091-6490}, } @article {pmid30249639, year = {2018}, author = {Guellil, M and Kersten, O and Namouchi, A and Bauer, EL and Derrick, M and Jensen, AØ and Stenseth, NC and Bramanti, B}, title = {Genomic blueprint of a relapsing fever pathogen in 15th century Scandinavia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10422-10427}, pmid = {30249639}, issn = {1091-6490}, mesh = {Adult ; Animals ; Bacterial Proteins/*genetics ; Borrelia/classification/*genetics/pathogenicity ; Child ; Female ; *Genome, Bacterial ; History, 15th Century ; Humans ; *Metagenomics ; Phylogeny ; Relapsing Fever/*genetics/history/microbiology ; Scandinavian and Nordic Countries ; }, abstract = {Louse-borne relapsing fever (LBRF) is known to have killed millions of people over the course of European history and remains a major cause of mortality in parts of the world. Its pathogen, Borrelia recurrentis, shares a common vector with global killers such as typhus and plague and is known for its involvement in devastating historical epidemics such as the Irish potato famine. Here, we describe a European and historical genome of Brecurrentis, recovered from a 15th century skeleton from Oslo. Our distinct European lineage has a discrete genomic makeup, displaying an ancestral oppA-1 gene and gene loss in antigenic variation sites. Our results illustrate the potential of ancient DNA research to elucidate dynamics of reductive evolution in a specialized human pathogen and to uncover aspects of human health usually invisible to the archaeological record.}, } @article {pmid30249638, year = {2018}, author = {Wang, M and Stidham, TA and Zhou, Z}, title = {A new clade of basal Early Cretaceous pygostylian birds and developmental plasticity of the avian shoulder girdle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10708-10713}, pmid = {30249638}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; Birds/anatomy & histology/*physiology ; *Fossils ; *Osteogenesis ; Paleontology ; Phylogeny ; Shoulder/anatomy & histology/*physiology ; }, abstract = {Early members of the clade Pygostylia (birds with a short tail ending in a compound bone termed "pygostyle") are critical for understanding how the modern avian bauplan evolved from long-tailed basal birds like Archaeopteryx However, the currently limited known diversity of early branching pygostylians obscures our understanding of this major transition in avian evolution. Here, we describe a basal pygostylian, Jinguofortis perplexus gen. et sp. nov., from the Early Cretaceous of China that adds important information about early members of the short-tailed bird group. Phylogenetic analysis recovers a clade (Jinguofortisidae fam. nov.) uniting Jinguofortis and the enigmatic basal avian taxon Chongmingia that represents the second earliest diverging group of the Pygostylia. Jinguofortisids preserve a mosaic combination of plesiomorphic nonavian theropod features such as a fused scapulocoracoid (a major component of the flight apparatus) and more derived flight-related morphologies including the earliest evidence of reduction in manual digits among birds. The presence of a fused scapulocoracoid in adult individuals independently evolved in Jinguofortisidae and Confuciusornithiformes may relate to an accelerated osteogenesis during chondrogenesis and likely formed through the heterochronic process of peramorphosis by which these basal taxa retain the scapulocoracoid of the nonavian theropod ancestors with the addition of flight-related modifications. With wings having a low aspect ratio and wing loading, Jinguofortis may have been adapted particularly to dense forest environments. The discovery of Jinguofortis increases the known ecomorphological diversity of basal pygostylians and highlights the importance of developmental plasticity for understanding mosaic evolution in early birds.}, } @article {pmid30249637, year = {2018}, author = {Kingsley, EP and Eliason, CM and Riede, T and Li, Z and Hiscock, TW and Farnsworth, M and Thomson, SL and Goller, F and Tabin, CJ and Clarke, JA}, title = {Identity and novelty in the avian syrinx.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10209-10217}, pmid = {30249637}, issn = {1091-6490}, support = {R01 HD087234/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Birds/*anatomy & histology/*physiology ; Fossils ; Larynx/anatomy & histology/physiology ; Phylogeny ; Respiratory System/anatomy & histology ; Trachea/*anatomy & histology/physiology ; Vocal Cords ; Vocalization, Animal ; }, abstract = {In its most basic conception, a novelty is simply something new. However, when many previously proposed evolutionary novelties have been illuminated by genetic, developmental, and fossil data, they have refined and narrowed our concept of biological "newness." For example, they show that these novelties can occur at one or multiple levels of biological organization. Here, we review the identity of structures in the avian vocal organ, the syrinx, and bring together developmental data on airway patterning, structural data from across tetrapods, and mathematical modeling to assess what is novel. In contrast with laryngeal cartilages that support vocal folds in other vertebrates, we find no evidence that individual cartilage rings anchoring vocal folds in the syrinx have homology with any specific elements in outgroups. Further, unlike all other vertebrate vocal organs, the syrinx is not derived from a known valve precursor, and its origin involves a transition from an evolutionary "spandrel" in the respiratory tract, the site where the trachea meets the bronchi, to a target for novel selective regimes. We find that the syrinx falls into an unusual category of novel structures: those having significant functional overlap with the structures they replace. The syrinx, along with other evolutionary novelties in sensory and signaling modalities, may more commonly involve structural changes that contribute to or modify an existing function rather than those that enable new functions.}, } @article {pmid30249636, year = {2018}, author = {Wang, CA and Munoz, DP}, title = {Neural basis of location-specific pupil luminance modulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10446-10451}, pmid = {30249636}, issn = {1091-6490}, support = {MOP-FDN-148418//Canadian Institutes of Health Research/International ; }, mesh = {Action Potentials ; Animals ; Macaca mulatta ; Male ; *Nerve Net ; *Neural Pathways ; Neurons/cytology/*physiology ; Photic Stimulation ; Pupil/*physiology ; Saccades/*physiology ; Superior Colliculi/cytology/*physiology ; }, abstract = {Spatial attention enables us to focus visual processing toward specific locations or stimuli before the next fixation. Recent evidence has suggested that local luminance at the spatial locus of attention or saccade preparation influences pupil size independent of global luminance levels. However, it remains to be determined which neural pathways produce this location-specific modulation of pupil size. The intermediate layers of the midbrain superior colliculus (SC) form part of the network of brain areas involved in spatial attention and modulation of pupil size. Here, we demonstrated that pupil size was altered according to local luminance level at the spatial location corresponding to a microstimulated location in the intermediate SC (SCi) map of monkeys. Moreover, local SCi inactivation through injection of lidocaine reversed this local luminance modulation. Our findings reveal a causal role of the SCi in preparing pupil size for local luminance conditions at the next saccadic goal.}, } @article {pmid30249635, year = {2018}, author = {Motta, EVS and Raymann, K and Moran, NA}, title = {Glyphosate perturbs the gut microbiota of honey bees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10305-10310}, pmid = {30249635}, issn = {1091-6490}, support = {R01 GM108477/GM/NIGMS NIH HHS/United States ; }, mesh = {3-Phosphoshikimate 1-Carboxyvinyltransferase/antagonists & inhibitors/metabolism ; Animals ; Bees/drug effects/*microbiology ; Enzyme Inhibitors/toxicity ; Escherichia coli/genetics/growth & development ; Gastrointestinal Microbiome/*drug effects/genetics ; Glycine/*analogs & derivatives/toxicity ; Neisseriaceae/drug effects/metabolism ; Phylogeny ; RNA, Ribosomal, 16S ; Serratia/pathogenicity ; }, abstract = {Glyphosate, the primary herbicide used globally for weed control, targets the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) enzyme in the shikimate pathway found in plants and some microorganisms. Thus, glyphosate may affect bacterial symbionts of animals living near agricultural sites, including pollinators such as bees. The honey bee gut microbiota is dominated by eight bacterial species that promote weight gain and reduce pathogen susceptibility. The gene encoding EPSPS is present in almost all sequenced genomes of bee gut bacteria, indicating that they are potentially susceptible to glyphosate. We demonstrated that the relative and absolute abundances of dominant gut microbiota species are decreased in bees exposed to glyphosate at concentrations documented in the environment. Glyphosate exposure of young workers increased mortality of bees subsequently exposed to the opportunistic pathogen Serratia marcescens Members of the bee gut microbiota varied in susceptibility to glyphosate, largely corresponding to whether they possessed an EPSPS of class I (sensitive to glyphosate) or class II (insensitive to glyphosate). This basis for differences in sensitivity was confirmed using in vitro experiments in which the EPSPS gene from bee gut bacteria was cloned into Escherichia coli All strains of the core bee gut species, Snodgrassella alvi, encode a sensitive class I EPSPS, and reduction in S. alvi levels was a consistent experimental result. However, some S. alvi strains appear to possess an alternative mechanism of glyphosate resistance. Thus, exposure of bees to glyphosate can perturb their beneficial gut microbiota, potentially affecting bee health and their effectiveness as pollinators.}, } @article {pmid30249306, year = {2018}, author = {Tadesse, T and Berhane, T and Abraha, TH and Gidey, B and Hagos, E and Grum, T and Gerensea, H}, title = {Blood donation practice and associated factors among health professionals in Tigray regional state public hospitals, northern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {677}, pmid = {30249306}, issn = {1756-0500}, mesh = {Adult ; *Blood Donors ; Cross-Sectional Studies ; Ethiopia ; Female ; Health Knowledge, Attitudes, Practice ; *Health Personnel ; *Hospitals, Public ; Humans ; Male ; Young Adult ; }, abstract = {OBJECTIVE: The demand for blood and blood products are increasing in all part of the globe, especially in the developing nations. However, there is limited information on the level of blood donation practice and their related factors. Therefore, assessing the level of blood donation practice and its determinant factors among health professionals have a paramount importance in designing an effective strategy for sustaining adequate and safe blood provision in the hospitals.

RESULTS: Out of 556 health professionals, 266 (47.8%) had ever donated blood in their life time. Age above 30 years (AOR = 2.756 95% CI 1.055-7.197), married health professionals (AOR = 1.729 95% CI 1.091-2.739), health professionals' knowledge of blood donation (AOR = 3.403 95% CI 2.296-5.044), health professionals' attitude towards blood donation (AOR = 3.41 95% CI 2.320-5.041) and health professionals who attend degree education (AOR = 0.315 95% CI 0.104-0.950) were significantly associated with blood donation behavior of health professionals. The magnitude of blood donation practice was found low. Therefore, the Ethiopian Red Cross Society and ministry of health should continue increasing the attitude and knowledge of health professionals toward blood donation practices are the key avenues interventions.}, } @article {pmid30249291, year = {2018}, author = {Yimama, M and Jarso, H and Desse, TA}, title = {Determinants of drug-related problems among ambulatory type 2 diabetes patients with hypertension comorbidity in Southwest Ethiopia: a prospective cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {679}, pmid = {30249291}, issn = {1756-0500}, mesh = {Adult ; Aged ; Comorbidity ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/complications/*drug therapy ; *Drug-Related Side Effects and Adverse Reactions ; Ethiopia ; Humans ; Hypertension/complications/*drug therapy ; Male ; Middle Aged ; Prospective Studies ; }, abstract = {OBJECTIVE: The aim of this study was to assess drug-related problems and its determinants in type 2 diabetes patients with hypertension co-morbidity.

RESULTS: A total of 300 type 2 diabetes patients with hypertension co-morbidity were studied. The majority of participants, 194 (64.7%), were males. Mean age of the participants was 54.44 ± 11.68 years. The mean durations of diabetes and hypertension were 5.37 ± 4.79 and 5.15 ± 4.65 years respectively. The most commonly prescribed antidiabetic medications were metformin in 200 (66.7%) and insulin 126 (42%) of the participants. Enalapril was the most commonly prescribed antihypertensive medication; 272 (90.7%). Aspirin was prescribed to 182 (60.7%) participants. Statins were prescribed to one-third (65.67%) of the participants. Eighty-five (28.3%) participants had diabetes related complications other than hypertension. A total of 494 drug related problems were identified. The mean number of drug related problems was 1.65 ± 1.05. The most common drug related problems were need for additional drug therapy (29.35%), ineffective drug (27.94%) and dose too low (15.8%). Independent predictors of drug related problems were age 41-60 years (AOR = 6.87, 95% CI 2.63-17.93), age > 60 years (AOR = 5.85, 95% CI 2.15-15.93) and the presence of comorbidity (AOR = 3.0, 95% CI 1.11-8.16).}, } @article {pmid30249286, year = {2018}, author = {Echodu, R and Edema, H and Malinga, GM and Hendy, A and Colebunders, R and Moriku Kaducu, J and Ovuga, E and Haesaert, G}, title = {Is nodding syndrome in northern Uganda linked to consumption of mycotoxin contaminated food grains?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {678}, pmid = {30249286}, issn = {1756-0500}, mesh = {Child ; Edible Grain ; *Food Contamination ; Humans ; Mycotoxins/*adverse effects ; Nodding Syndrome/*etiology ; South Sudan ; Uganda ; }, abstract = {OBJECTIVE: Nodding syndrome (NS) is a type of epilepsy characterized by repeated head-nodding seizures that appear in previously healthy children between 3 and 18 years of age. In 2012, during a WHO International Meeting on NS in Kampala, Uganda, it was recommended that fungal contamination of foods should be investigated as a possible cause of the disease. We therefore aimed to assess whether consumption of fungal mycotoxins contributes to NS development.

RESULTS: We detected similar high levels of total aflatoxin and ochratoxin in mostly millet, sorghum, maize and groundnuts in both households with and without children with NS. Furthermore, there was no significant association between concentrations of total aflatoxin, ochratoxin and doxynivalenol and the presence of children with NS in households. In conclusion, our results show no supporting evidence for the association of NS with consumption of mycotoxins in contaminated foods.}, } @article {pmid30249275, year = {2018}, author = {He, Y and Wu, W and Wu, S and Zheng, HM and Li, P and Sheng, HF and Chen, MX and Chen, ZH and Ji, GY and Zheng, ZD and Mujagond, P and Chen, XJ and Rong, ZH and Chen, P and Lyu, LY and Wang, X and Xu, JB and Wu, CB and Yu, N and Xu, YJ and Yin, J and Raes, J and Ma, WJ and Zhou, HW}, title = {Linking gut microbiota, metabolic syndrome and economic status based on a population-level analysis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {172}, pmid = {30249275}, issn = {2049-2618}, abstract = {BACKGROUND: The metabolic syndrome (MetS) epidemic is associated with economic development, lifestyle transition and dysbiosis of gut microbiota, but these associations are rarely studied at the population scale. Here, we utilised the Guangdong Gut Microbiome Project (GGMP), the largest Eastern population-based gut microbiome dataset covering individuals with different economic statuses, to investigate the relationships between the gut microbiome and host physiology, diet, geography, physical activity and socioeconomic status.

RESULTS: At the population level, 529 OTUs were significantly associated with MetS. OTUs from Proteobacteria and Firmicutes (other than Ruminococcaceae) were mainly positively associated with MetS, whereas those from Bacteroidetes and Ruminococcaceae were negatively associated with MetS. Two hundred fourteen OTUs were significantly associated with host economic status (140 positive and 74 negative associations), and 157 of these OTUs were also MetS associated. A microbial MetS index was formulated to represent the overall gut dysbiosis of MetS. The values of this index were significantly higher in MetS subjects regardless of their economic status or geographical location. The index values did not increase with increasing personal economic status, although the prevalence of MetS was significantly higher in people of higher economic status. With increased economic status, the study population tended to consume more fruits and vegetables and fewer grains, whereas meat consumption was unchanged. Sedentary time was significantly and positively associated with higher economic status. The MetS index showed an additive effect with sedentary lifestyle, as the prevalence of MetS in individuals with high MetS index values and unhealthy lifestyles was significantly higher than that in the rest of the population.

CONCLUSIONS: The gut microbiome is associated with MetS and economic status. A prolonged sedentary lifestyle, rather than Westernised dietary patterns, was the most notable lifestyle change in our Eastern population along with economic development. Moreover, gut dysbiosis and a Western lifestyle had an additive effect on increasing MetS prevalence.}, } @article {pmid30249271, year = {2018}, author = {Aanen, DK}, title = {The disposable male- the ultimate emancipation of females?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {106}, pmid = {30249271}, issn = {1741-7007}, mesh = {Animals ; Female ; *Isoptera ; Male ; *Reproduction ; Reproduction, Asexual ; }, abstract = {Sexual reproduction is costly compared to asexual reproduction, in particular because males generally contribute little to offspring. Research published today in BMC Biology shows that some populations of a termite species have disposed of males altogether. However, this need not necessarily be seen as a victory for the females, since males in most termite societies are active colony members that contribute their fair share to colony tasks.}, } @article {pmid30249269, year = {2018}, author = {Yashiro, T and Lo, N and Kobayashi, K and Nozaki, T and Fuchikawa, T and Mizumoto, N and Namba, Y and Matsuura, K}, title = {Loss of males from mixed-sex societies in termites.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {96}, pmid = {30249269}, issn = {1741-7007}, abstract = {BACKGROUND: Sexual reproduction is the norm in almost all animal species, and in many advanced animal societies, both males and females participate in social activities. To date, the complete loss of males from advanced social animal lineages has been reported only in ants and honey bees (Hymenoptera), whose workers are always female and whose males display no helping behaviors even in normal sexual species. Asexuality has not previously been observed in colonies of another major group of social insects, the termites, where the ubiquitous presence of both male and female workers and soldiers indicate that males play a critical role beyond that of reproduction.

RESULTS: Here, we report asexual societies in a lineage of the termite Glyptotermes nakajimai. We investigated the composition of mature colonies from ten distinct populations in Japan, finding six asexual populations characterized by a lack of any males in the reproductive, soldier, and worker castes of their colonies, an absence of sperm in the spermathecae of their queens, and the development of unfertilized eggs at a level comparable to that for the development of fertilized eggs in sexual populations of this species. Phylogenetic analyses indicated a single evolutionary origin of the asexual populations, with divergence from sampled sexual populations occurring about 14 million years ago. Asexual colonies differ from sexual colonies in having a more uniform head size in their all-female soldier caste, and fewer soldiers in proportion to other individuals, suggesting increased defensive efficiencies arising from uniform soldier morphology. Such efficiencies may have contributed to the persistence and spread of the asexual lineage. Cooperative colony foundation by multiple queens, the single-site nesting life history common to both the asexual and sexual lineages, and the occasional development of eggs without fertilization even in the sexual lineage are traits likely to have been present in the ancestors of the asexual lineage that may have facilitated the transition to asexuality.

CONCLUSIONS: Our findings demonstrate that completely asexual social lineages can evolve from mixed-sex termite societies, providing evidence that males are dispensable for the maintenance of advanced animal societies in which they previously played an active social role.}, } @article {pmid30249243, year = {2018}, author = {Wang, Y and Long, H and Yu, J and Dong, L and Wassef, M and Zhuo, B and Li, X and Zhao, J and Wang, M and Liu, C and Wen, Z and Chang, L and Chen, P and Wang, QF and Xu, X and Margueron, R and Li, G}, title = {Histone variants H2A.Z and H3.3 coordinately regulate PRC2-dependent H3K27me3 deposition and gene expression regulation in mES cells.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {107}, pmid = {30249243}, issn = {1741-7007}, support = {55008737/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {BACKGROUND: The hierarchical organization of eukaryotic chromatin plays a central role in gene regulation, by controlling the extent to which the transcription machinery can access DNA. The histone variants H3.3 and H2A.Z have recently been identified as key regulatory players in this process, but the underlying molecular mechanisms by which they permit or restrict gene expression remain unclear. Here, we investigated the regulatory function of H3.3 and H2A.Z on chromatin dynamics and Polycomb-mediated gene silencing.

RESULTS: Our ChIP-seq analysis reveals that in mouse embryonic stem (mES) cells, H3K27me3 enrichment correlates strongly with H2A.Z. We further demonstrate that H2A.Z promotes PRC2 activity on H3K27 methylation through facilitating chromatin compaction both in vitro and in mES cells. In contrast, PRC2 activity is counteracted by H3.3 through impairing chromatin compaction. However, a subset of H3.3 may positively regulate PRC2-dependent H3K27 methylation via coordinating depositions of H2A.Z to developmental and signaling genes in mES cells. Using all-trans retinoic acid (tRA)-induced gene as a model, we show that the dynamic deposition of H2A.Z and H3.3 coordinately regulates the PRC2-dependent H3K27 methylation by modulating local chromatin structure at the promoter region during the process of turning genes off.

CONCLUSIONS: Our study provides key insights into the mechanism of how histone variants H3.3 and H2A.Z function coordinately to finely tune the PRC2 enzymatic activity during gene silencing, through promoting or impairing chromosome compaction respectively.}, } @article {pmid30249235, year = {2018}, author = {Lu, HL and Xu, CX and Zeng, ZG and Du, WG}, title = {Environmental causes of between-population difference in growth rate of a high-altitude lizard.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {37}, pmid = {30249235}, issn = {1472-6785}, support = {XDA20050201//Strategic Priority Research Program of the Chinese Academy of Sciences/International ; XDB31000000//Strategic Priority Research Program of the Chinese Academy of Sciences/International ; Sino-BON//China's Biodiversity Observation Network/International ; }, abstract = {BACKGROUND: Ectothermic animals living in cold (high latitude or high elevation) regions are predicted to grow slower due to limited thermal opportunities for activity and food resources than those living in warm regions. However, the Qinghai toad-headed lizards (Phrynocephalus vlangalii) grow faster and reach a larger adult size at a high-elevation site than at a low-elevation site. In this study, we aimed to identify the genetic and environmental causes of this between-population difference in growth rate by conducting mark-recapture and common garden experiments on juvenile growth rate, and investigating the thermal environment, lizard body temperature, potential prey availability at the two elevation sites.

RESULTS: Compared with low-elevation individuals, high-elevation juvenile lizards had higher growth rates in the field, but grew at similar rates in the laboratory. High-elevation lizards had higher active body temperatures than low-elevation lizards despite similar air temperatures in the period of field investigation. The high-elevation site had relatively more and larger preys than the low-elevation site.

CONCLUSIONS: Inter-population difference in growth rate of P. vlangalii may primarily result from developmental plasticity in response to the difference in environmental resources, rather than genetic differentiation. The higher growth rate of high-elevation lizards is likely associated with higher potential food availability and higher active body temperatures.}, } @article {pmid30249207, year = {2018}, author = {Vedelek, V and Bodai, L and Grézal, G and Kovács, B and Boros, IM and Laurinyecz, B and Sinka, R}, title = {Analysis of Drosophila melanogaster testis transcriptome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {697}, pmid = {30249207}, issn = {1471-2164}, support = {NF101001//NKFIH/ ; K112294//NKFIH/ ; GINOP-2.3.2-15-2016-00032//NKFIH/ ; GINOP-2.3.2-15-2016-00035//NKFIH/ ; }, mesh = {Animals ; Cytoskeletal Proteins/genetics/metabolism ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/enzymology/*genetics/metabolism ; Gene Expression Profiling ; Gene Ontology ; Heat-Shock Proteins/metabolism ; Male ; Metabolic Networks and Pathways/genetics ; Proteasome Endopeptidase Complex/metabolism ; RNA, Long Noncoding/metabolism ; Sequence Analysis, RNA ; Testis/enzymology/metabolism ; *Transcriptome ; Ubiquitin/metabolism ; }, abstract = {BACKGROUND: The formation of matured and individual sperm involves a series of molecular and spectacular morphological changes of the developing cysts in Drosophila melanogaster testis. Recent advances in RNA Sequencing (RNA-Seq) technology help us to understand the complexity of eukaryotic transcriptomes by dissecting different tissues and developmental stages of organisms. To gain a better understanding of cellular differentiation of spermatogenesis, we applied RNA-Seq to analyse the testis-specific transcriptome, including coding and non-coding genes.

RESULTS: We isolated three different parts of the wild-type testis by dissecting and cutting the different regions: 1.) the apical region, which contains stem cells and developing spermatocytes 2.) the middle region, with enrichment of meiotic cysts 3.) the basal region, which contains elongated post-meiotic cysts with spermatids. Total RNA was isolated from each region and analysed by next-generation sequencing. We collected data from the annotated 17412 Drosophila genes and identified 5381 genes with significant transcript accumulation differences between the regions, representing the main stages of spermatogenesis. We demonstrated for the first time the presence and region specific distribution of 2061 lncRNAs in testis, with 203 significant differences. Using the available modENCODE RNA-Seq data, we determined the tissue specificity indices of Drosophila genes. Combining the indices with our results, we identified genes with region-specific enrichment in testis.

CONCLUSION: By multiple analyses of our results and integrating existing knowledge about Drosophila melanogaster spermatogenesis to our dataset, we were able to describe transcript composition of different regions of Drosophila testis, including several stage-specific transcripts. We present searchable visualizations that can facilitate the identification of new components that play role in the organisation and composition of different stages of spermatogenesis, including the less known, but complex regulation of post-meiotic stages.}, } @article {pmid30249206, year = {2018}, author = {Brito, AF and Melo, FL and Ardisson-Araújo, DMP and Sihler, W and Souza, ML and Ribeiro, BM}, title = {Genome-wide diversity in temporal and regional populations of the betabaculovirus Erinnyis ello granulovirus (ErelGV).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {698}, pmid = {30249206}, issn = {1471-2164}, support = {407908/2013-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 483677/2012-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 193.001.532/2016//Fundação de Apoio à Pesquisa do Distrito Federal/ ; }, mesh = {Baculoviridae/classification/*genetics/isolation & purification ; *Genome, Viral ; Phylogeny ; *Polymorphism, Genetic ; Viral Proteins/genetics ; }, abstract = {BACKGROUND: Erinnyis ello granulovirus (ErelGV) is a betabaculovirus infecting caterpillars of the sphingid moth E. ello ello (cassava hornworm), an important pest of cassava crops (Manihot esculenta). In this study, the genome of seven field isolates of the virus ErelGV were deep sequenced and their inter- and intrapopulational sequence diversity were analyzed.

RESULTS: No events of gene gain/loss or translocations were observed, and indels were mainly found within highly repetitive regions (direct repeats, drs). A naturally occurring isolate from Northern Brazil (Acre State, an Amazonian region) has shown to be the most diverse population, with a unique pattern of polymorphisms. Overall, non-synonymous substitutions were found all over the seven genomes, with no specific gathering of mutations on hotspot regions. Independently of their sizes, some ORFs have shown higher levels of non-synonymous changes than others. Non-core genes of known functions and structural genes were among the most diverse ones; and as expected, core genes were the least variable genes. We observed remarkable differences on diversity of paralogous genes, as in multiple copies of p10, fgf, and pep. Another important contrast on sequence diversity was found on genes encoding complex subunits and/or involved in the same biological processes, as late expression factors (lefs) and per os infectivity factors (pifs). Interestingly, several polymorphisms in coding regions lie on sequences encoding specific protein domains.

CONCLUSIONS: By comparing and integrating information about inter- and intrapopulational diversity of viral isolates, we provide a detailed description on how evolution operates on field isolates of a betabaculovirus. Our results revealed that 35-41% of the SNPs of ErelGV lead to amino acid changes (non-synonymous substitutions). Some genes, especially non-core genes of unknown functions, tend to accumulate more mutations, while core genes evolve slowly and are more conserved. Additional studies would be necessary to understand the actual effects of such gene variations on viral infection and fitness.}, } @article {pmid30249194, year = {2018}, author = {Alexeeva, S and Guerra Martínez, JA and Spus, M and Smid, EJ}, title = {Spontaneously induced prophages are abundant in a naturally evolved bacterial starter culture and deliver competitive advantage to the host.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {120}, pmid = {30249194}, issn = {1471-2180}, abstract = {BACKGROUND: In complex microbial ecosystems such as the marine environment, the gastrointestinal tract, but also in mixed culture fermentations, bacteriophages are frequently found to be a part of the microbial community. Moreover, prophages or prophage-like elements are frequently identified in sequenced bacterial genomes. The mixed undefined starter cultures represent an ecosystem which is shaped by long term evolution under relatively defined environmental conditions and provides an interesting model to study co-evolution of phages and their hosts as well as the impact of diversity on microbial community stability.

RESULTS: In the present study we investigated the presence, identity and behaviour of prophages in lactococci being part of a complex cheese starter culture. Genome analysis of representative strains of the 7 genetic lineages of Lactococcus lactis constituting the culture indicated the presence of prophages in all strains. Exposure of potential lysogens to mitomycin C confirmed the release of ~ 1010·ml- 1 phage particles from all tested strains. Furthermore, phages were also released in substantial amounts due to spontaneous induction: more than 108·ml- 1 phage particles were present in cultures under non-inducing conditions. This observation suggests continuous release of phage particles by the lactococci. The released bacteriophages exhibited an unusual morphology. For most strains tested, tailless icosahedral phage heads were found. The competitive advantage of lysogens compared to their cured derivatives and their high abundance in the culture suggests that the released tailless bacteriophages play an important role in the ecosystem.

CONCLUSIONS: The results of this study indicate that chromosomal genetic elements are active participants in the stable complex microbial community of the starter culture. We show that prophages are abundant in such a community, are produced continuously in large amounts and, despite the huge metabolic burden imposed on the cells by phage particle production, provide a selective advantage to the host.}, } @article {pmid30249189, year = {2018}, author = {Bräuning, S and Catanach, A and Lord, JM and Bicknell, R and Macknight, RC}, title = {Comparative transcriptome analysis of the wild-type model apomict Hieracium praealtum and its loss of parthenogenesis (lop) mutant.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {206}, pmid = {30249189}, issn = {1471-2229}, support = {Priming Partnerships fund//University of Otago/ ; Post graduate scholarship//University of Otago/ ; }, mesh = {Apomixis/*genetics ; Asteraceae/*genetics ; Endosperm/genetics/growth & development ; Epigenesis, Genetic ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Genetic Markers ; Indoleacetic Acids/metabolism ; Mutation ; Plant Proteins/genetics ; Pollination ; Seeds/genetics/growth & development ; }, abstract = {BACKGROUND: Asexual seed formation (apomixis) has been observed in diverse plant families but is rare in crop plants. The generation of apomictic crops would revolutionize agriculture, as clonal seed production provides a low cost and efficient way to produce hybrid seed. Hieracium (Asteraceae) is a model system for studying the molecular components of gametophytic apomixis (asexual seed reproduction).

RESULTS: In this study, a reference transcriptome was produced from apomictic Hieracium undergoing the key apomictic events of apomeiosis, parthenogenesis and autonomous endosperm development. In addition, transcriptome sequences from pre-pollination and post-pollination stages were generated from a loss of parthenogenesis (lop) mutant accession that exhibits loss of parthenogenesis and autonomous endosperm development. The transcriptome is composed of 147,632 contigs, 50% of which were annotated with orthologous genes and their probable function. The transcriptome was used to identify transcripts differentially expressed during apomictic and pollination dependent (lop) seed development. Gene Ontology enrichment analysis of differentially expressed transcripts showed that an important difference between apomictic and pollination dependent seed development was the expression of genes relating to epigenetic gene regulation. Genes that mark key developmental stages, i.e. aposporous embryo sac development and seed development, were also identified through their enhanced expression at those stages.

CONCLUSION: The production of a comprehensive floral reference transcriptome for Hieracium provides a valuable resource for research into the molecular basis of apomixis and the identification of the genes underlying the LOP locus.}, } @article {pmid30249188, year = {2018}, author = {Wang, Y and Jiang, W and Ye, W and Fu, C and Gitzendanner, MA and Soltis, PS and Soltis, DE and Qiu, Y}, title = {Evolutionary insights from comparative transcriptome and transcriptome-wide coalescence analyses in Tetrastigma hemsleyanum.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {208}, pmid = {30249188}, issn = {1471-2229}, support = {LY14C020002//Zhejiang Provincial Natural Science Foundation of China/ ; 31700193//National Natural Science Foundation of China/ ; 31370241//National Natural Science Foundation of China/ ; 31461123001//Biodiversity International Collaborative Project of NSFC-NSF/ ; }, mesh = {Adaptation, Biological/genetics ; *Biological Evolution ; DNA, Chloroplast ; Expressed Sequence Tags ; *Gene Expression Profiling ; Molecular Sequence Annotation ; Multilocus Sequence Typing ; Plant Proteins/genetics ; Vitaceae/*genetics/physiology ; }, abstract = {BACKGROUND: Tetrastigma hemsleyanum is of great medicinal importance and used as a model system to address the evolutionary history of warm-temperate evergreen (WTE) forest biomes in East Asia over Neogene time scales. However, further studies on the neutral and adaptive divergence processes of T. hemsleyanum are currently impeded by a lack of genomic resources. In this study, we de novo assembled and annotated a reference transcriptome for two cpDNA lineages (Central-South-East vs. Southwest) of T. hemsleyanum. We further used comparative genomic and multilocus coalescent approaches to investigate the tempo and mode of lineage diversification in T. hemsleyanum.

RESULTS: A total of 52,838 and 65,197 unigenes with an N50 of 1,667 and 1,841 bp for Central-South-East (CSE) and Southwest (SW) lineages, respectively, were recovered, and 6,692 putative orthologs were identified between the two lineages. Estimation of Ka/Ks ratios for these orthologs revealed that ten genes had Ka/Ks values significantly greater than 0.5 (P < 0.05), whereas 2,099 (Ka/Ks < 0.5, P < 0.05) were inferred to be under purifying selection. Based on three bioinformatic strategies, we identified a total of 1,018 single-copy nuclear genes (SCNGs) from the orthologs. We successfully designed eight nuclear gene primer pairs with high intraspecific variation (e.g. hT = 0.923, πT = 1.68×10-3), when surveyed across a subset of T. hemsleyanum individuals. Concordant with the previous cpDNA data, the haplotype networks constructed for most nuclear gene loci clearly identified the two lineages. A multilocus coalescence analysis suggested that the separation between the two lineages appears to have occurred during the mid-Pliocene. Despite their ancient divergence, both lineages experienced expansion at rather localized scales and have continued to exchange genes at a low rate.

CONCLUSIONS: This study demonstrated the utility of transcriptome sequencing as a basis for SCNG development in non-model species and the advantages of integrating multiple nuclear loci for phylogeographic and phylogenetic studies.}, } @article {pmid30249187, year = {2018}, author = {Yang, Y and Bao, S and Zhou, X and Liu, J and Zhuang, Y}, title = {The key genes and pathways related to male sterility of eggplant revealed by comparative transcriptome analysis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {209}, pmid = {30249187}, issn = {1471-2229}, support = {31672145//National Natural Science Foundation of China/ ; 31701932//National Natural Science Foundation of China/ ; }, mesh = {Cluster Analysis ; Flowers/physiology ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Gene Ontology ; Metabolic Networks and Pathways/genetics ; Models, Genetic ; Plant Infertility/*genetics ; Plant Proteins/genetics ; Reproducibility of Results ; Sequence Analysis, RNA ; Solanum melongena/*genetics/physiology ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Male sterility (MS) is an effective tool for hybrid production. Although MS has been widely reported in other plants, such as Arabidopsis and rice, the molecular mechanism of MS in eggplant is largely unknown. To understand the mechanism, the comparative transcriptomic file of MS line and its maintainer line was analyzed with the RNA-seq technology.

RESULTS: A total of 11,7695 unigenes were assembled and 19,652 differentially expressed genes (DEGs) were obtained. The results showed that 1,716 DEGs were shared in the three stages. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis indicated that these DEGs were mainly involved in oxidation-reduction, carbohydrate and amino acid metabolism. Moreover, transcriptional regulation was also the impact effector for MS and anther development. Weighted correlation network analysis (WGCNA) showed two modules might be responsible for MS, which was similar to hierarchical cluster analysis.

CONCLUSIONS: A number of genes and pathways associated with MS were found in this study. This study threw light on the molecular mechanism of MS and identified several key genes related to MS in eggplant.}, } @article {pmid30249186, year = {2018}, author = {Hu, D and Wang, C and Wang, S and Tang, X and Duan, C and Zhang, S and Suo, J and Deng, M and Lv, Y and Suo, X and Liu, X}, title = {Comparative transcriptome analysis of Eimeria maxima (Apicomplexa: Eimeriidae) suggests DNA replication activities correlating with its fecundity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {699}, pmid = {30249186}, issn = {1471-2164}, support = {31472180//National Natural Science Foundation of China/ ; 31572507//National Natural Science Foundation of China/ ; 31772728//National Natural Science Foundation of China/ ; CARS-43//China Agriculture Research System/ ; 2015-Z31//Chinese Ministry of Agriculture/ ; }, mesh = {Animals ; Chickens/parasitology ; *DNA Replication ; Eimeria/*genetics/growth & development/immunology/pathogenicity ; Fertility/genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Chicken coccidiosis, caused by the infection of Eimeria species, leads to important economic losses to the poultry industry. Vaccination with attenuated live parasites seems to be the best way to control this disease. Attenuated eimerian parasites with shortened prepatent times show great changes in intracellular development compared to their parent strains but the mechanisms involved in these biological differences are still unclear.

RESULTS: In this study, we obtained a precocious line of E. maxima by sequential selection of 22 generations of early shed oocysts in chickens and performed a comparative transcriptome analysis of three different developmental stages of the precocious line and its parent strain using Illumina high-throughput sequencing. Our E. maxima precocious line showed decreased pathogenicity, reduced fecundity and a greatly shorted prepatent time of only 98 h. We found that typical gene changes in the stage development from unsporulated to sporulated oocyst and from sporulated oocyst to merozoite were marked by upregulated organelle genes and protein translation related genes, respectively. Additionally, major differences between the precocious line and its parent strain were detected in the merozoite stage, characterized by downregulated genes involved in protein cleavage and DNA replication activities.

CONCLUSIONS: Our study generated and characterized an E. maxima precocious line, illustrating gene expression landscapes during parasite development by transcriptome analysis. We also show that the suppressed DNA replication progress in the merozoite stage in the precocious line may result in its reduced fecundity. These results provide the basis for a better understanding of the mechanism of precocity in Eimeria species, which can be useful in studies in early gametocytogenesis in apicomplexan parasites.}, } @article {pmid30249185, year = {2018}, author = {Zhang, Y and Su, J and Cheng, D and Wang, R and Mei, Y and Hu, H and Shen, W and Zhang, Y}, title = {Nitric oxide contributes to methane-induced osmotic stress tolerance in mung bean.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {207}, pmid = {30249185}, issn = {1471-2229}, support = {KYCX17_0660//Postgraduate Research & Practice Innovation Program of Jiangsu Province/ ; KYTZ201402//Fundamental Research Funds for the Central Universities/ ; CARS-08//China Agriculture Research System/ ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, mesh = {Benzoates/pharmacology ; Cyclic N-Oxides/pharmacology ; Germination/drug effects ; Imidazoles/pharmacology ; Methane/*metabolism/pharmacology ; NG-Nitroarginine Methyl Ester/pharmacology ; Nitric Oxide/*metabolism ; Nitroprusside/pharmacology ; Osmotic Pressure/*physiology ; Oxidation-Reduction ; Polyethylene Glycols/pharmacology ; Starch/metabolism ; Tungsten Compounds/pharmacology ; Vigna/drug effects/*physiology ; }, abstract = {BACKGROUND: Osmotic stress is a major abiotic stress limiting crop production by affecting plant growth and development. Although previous reports discovered that methane (CH4) has a beneficial effect on osmotic stress, the corresponding downstream signal(s) is still elusive.

RESULTS: Polyethylene glycol (PEG) treatment progressively stimulated the production of CH4 in germinating mung bean seeds. Exogenous CH4 and sodium nitroprusside (SNP) not only triggered nitric oxide (NO) production in PEG-stressed plants, but also alleviated the inhibition of seed germination. Meanwhile, amylase activity was activated, thus accelerating the formation of reducing sugar and total soluble sugar. Above responses could be impaired by NO scavenger(s), suggesting that CH4-induced stress tolerance was dependent on NO. Subsequent tests showed that CH4 could reestablish redox balance in a NO-dependent fashion. The addition of inhibitors of the nitrate reductase (NR) and NO synthase in mammalian (NOS), suggested that NR and NOS-like protein might be partially involved in CH4-alleviated seed germination inhibition. In vitro and scavenger tests showed that NO-mediated S-nitrosylation might be associated with above CH4 responses.

CONCLUSIONS: Together, these results indicated an important role of endogenous NO in CH4-enhanced plant tolerance against osmotic stress, and NO-regulated redox homeostasis and S-nitrosylation might be involved in above CH4 action.}, } @article {pmid30249184, year = {2018}, author = {Byloos, B and Monsieurs, P and Mysara, M and Leys, N and Boon, N and Van Houdt, R}, title = {Characterization of the bacterial communities on recent Icelandic volcanic deposits of different ages.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {122}, pmid = {30249184}, issn = {1471-2180}, abstract = {BACKGROUND: Basalt is the most common igneous rock on the Earth's surface covering. Basalt-associated microorganisms drive the cycling and sequestration of different elements such as nitrogen, carbon and other nutrients, which facilitate subsequent pioneer and plant development, impacting long-term regulation of the Earth's temperature and biosphere. The initial processes of colonization and subsequent rock weathering by microbial communities are still poorly understood and relatively few data are available on the diversity and richness of the communities inhabiting successive and chronological lava flows. In this study, the bacterial communities present on lava deposits from different eruptions of the 1975-84 Krafla Fires (32-, 35- and 39-year old, respectively) at the Krafla, Iceland, were determined.

RESULTS: Three sites were sampled for each deposit (32-, 35- and 39-year old), two proximal sites (at 10 m distance) and one more distant site (at 100 m from the two other sites). The determined chemical composition and metal concentrations were similar for the three basalt deposits. No significant differences were observed in the total number of cells in each flow. 16S rRNA gene amplicon sequencing showed that the most abundant classified phylum across the 3 flows was Proteobacteria, although predominance of Acidobacteria, Actinobacteria and Firmicutes was observed for some sampling sites. In addition, a considerable fraction of the operational taxonomic units remained unclassified. Alpha diversity (Shannon, inverse Simpson and Chao), HOMOVA and AMOVA only showed a significant difference for Shannon between the 32- and 39-year old flow (p < 0.05). Nonmetric multidimensional scaling (NMDS) analysis showed that age significantly (p = 0.026) influenced the leftward movement along NMDS axis 1.

CONCLUSIONS: Although NMDS indicated that the (relatively small) age difference of the deposits appeared to impact the bacterial community, this analysis was not consistent with AMOVA and HOMOVA, indicating no significant difference in community structure. The combined results drive us to conclude that the (relatively small) age differences of the deposits do not appear to be the main factor shaping the microbial communities. Probably other factors such as spatial heterogeneity, associated carbon content, exogenous rain precipitations and wind also affect the diversity and dynamics.}, } @article {pmid30249183, year = {2018}, author = {Meneghetti, KL and do Canto Canabarro, M and Otton, LM and Dos Santos Hain, T and Geimba, MP and Corção, G}, title = {Bacterial contamination of human skin allografts and antimicrobial resistance: a skin bank problem.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {121}, pmid = {30249183}, issn = {1471-2180}, abstract = {BACKGROUND: Bacterial contamination remains the major problem in skin banks, even after antimicrobial treatment, and results in high rates of tissue discarding. This study aimed to analyze bacterial contamination in 32 human skin allografts from the skin bank of Dr. Roberto Corrêa Chem from the Hospital Complex Santa Casa de Misericórdia de Porto Alegre. These samples were already discarded due to microbial contamination. The identification of the bacteria isolated from skin allografts was performed by matrix assisted laser desorption ionization-time of flight. The antimicrobial susceptibility of the isolates to six different classes of antimicrobials was determined using the disk-diffusion agar method, and the evaluation of the inhibitory potential was determined by the minimal inhibitory concentration (50/90) of antimicrobials already used in the skin bank and those that most isolates were susceptible to.

RESULTS: A total of 21 (65.6%) skin samples were contaminated with Gram-positive bacteria: 1 (4.7%) with Paenibacillus sp., 12 (61.9%) with Bacillus sp., 6 (28.5%) with Staphylococcus sp., and 2 (9.5%) with Bacillus sp. and Staphylococcus sp. Several resistance profiles, including multiresistance, were found among the isolates. Most of the isolates were susceptible to at least one of the antimicrobials used in the skin bank. All isolates were susceptible to amikacin, gentamicin, and tetracycline, which demonstrated the best inhibitory activities against the isolates and were considered as potential candidates for new antimicrobial treatments.

CONCLUSIONS: Bacillus, Paenibacillus, and Staphylococcus were isolated from the skin allografts, thus demonstrating the predominance of Gram-positive bacteria contamination. Other factors not related to the resistance phenotype may also be involved in the persistence of bacterial isolates in the skin allografts after antibiotic treatment. Gentamicin, amikacin, and tetracycline can be considered as an option for a more effective treatment cocktail.}, } @article {pmid30249182, year = {2018}, author = {Cavalcanti, GS and Shukla, P and Morris, M and Ribeiro, B and Foley, M and Doane, MP and Thompson, CC and Edwards, MS and Dinsdale, EA and Thompson, FL}, title = {Rhodoliths holobionts in a changing ocean: host-microbes interactions mediate coralline algae resilience under ocean acidification.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {701}, pmid = {30249182}, issn = {1471-2164}, mesh = {Biodiversity ; Hydrogen-Ion Concentration ; Metagenome ; *Microbiota/genetics ; Oceans and Seas ; Photosynthesis ; Rhodophyta/metabolism/*microbiology/physiology ; Seawater/chemistry/microbiology ; Stress, Physiological ; }, abstract = {BACKGROUND: Life in the ocean will increasingly have to contend with a complex matrix of concurrent shifts in environmental properties that impact their physiology and control their life histories. Rhodoliths are coralline red algae (Corallinales, Rhodophyta) that are photosynthesizers, calcifiers, and ecosystem engineers and therefore represent important targets for ocean acidification (OA) research. Here, we exposed live rhodoliths to near-future OA conditions to investigate responses in their photosynthetic capacity, calcium carbonate production, and associated microbiome using carbon uptake, decalcification assays, and whole genome shotgun sequencing metagenomic analysis, respectively. The results from our live rhodolith assays were compared to similar manipulations on dead rhodolith (calcareous skeleton) biofilms and water column microbial communities, thereby enabling the assessment of host-microbiome interaction under climate-driven environmental perturbations.

RESULTS: Under high pCO2 conditions, live rhodoliths exhibited positive physiological responses, i.e. increased photosynthetic activity, and no calcium carbonate biomass loss over time. Further, whereas the microbiome associated with live rhodoliths remained stable and resembled a healthy holobiont, the microbial community associated with the water column changed after exposure to elevated pCO2.

CONCLUSIONS: Our results suggest that a tightly regulated microbial-host interaction, as evidenced by the stability of the rhodolith microbiome recorded here under OA-like conditions, is important for host resilience to environmental stress. This study extends the scarce comprehension of microbes associated with rhodolith beds and their reaction to increased pCO2, providing a more comprehensive approach to OA studies by assessing the host holobiont.}, } @article {pmid30249181, year = {2018}, author = {Hooper, WF and Walcott, BD and Wang, X and Bystroff, C}, title = {Fast design of arbitrary length loops in proteins using InteractiveRosetta.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {337}, pmid = {30249181}, issn = {1471-2105}, support = {R01 GM099827/GM/NIGMS NIH HHS/United States ; GM099827//National Institute of General Medical Sciences/ ; }, mesh = {Genetic Engineering ; INDEL Mutation/genetics ; Models, Molecular ; Protein Domains ; Protein Multimerization ; Protein Structure, Secondary ; Proteins/*chemistry ; *Software ; Time Factors ; }, abstract = {BACKGROUND: With increasing interest in ab initio protein design, there is a desire to be able to fully explore the design space of insertions and deletions. Nature inserts and deletes residues to optimize energy and function, but allowing variable length indels in the context of an interactive protein design session presents challenges with regard to speed and accuracy.

RESULTS: Here we present a new module (INDEL) for InteractiveRosetta which allows the user to specify a range of lengths for a desired indel, and which returns a set of low energy backbones in a matter of seconds. To make the loop search fast, loop anchor points are geometrically hashed using C α-C α and C β-C β distances, and the hash is mapped to start and end points in a pre-compiled random access file of non-redundant, protein backbone coordinates. Loops with superposable anchors are filtered for collisions and returned to InteractiveRosetta as poly-alanine for display and selective incorporation into the design template. Sidechains can then be added using RosettaDesign tools.

CONCLUSIONS: INDEL was able to find viable loops in 100% of 500 attempts for all lengths from 3 to 20 residues. INDEL has been applied to the task of designing a domain-swapping loop for T7-endonuclease I, changing its specificity from Holliday junctions to paranemic crossover (PX) DNA.}, } @article {pmid30249180, year = {2018}, author = {Minei, R and Hoshina, R and Ogura, A}, title = {De novo assembly of middle-sized genome using MinION and Illumina sequencers.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {700}, pmid = {30249180}, issn = {1471-2164}, mesh = {Chlorella/*genetics/metabolism ; Gene Expression Profiling ; Genome Size ; *Genome, Plant ; Models, Genetic ; Sequence Analysis, DNA/*methods ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: The plastid acquisition by secondary endosymbiosis is a driving force for the algal evolution, and the comparative genomics was required to examine the genomic change of symbiont. Therefore, we established a pipeline of a de novo assembly of middle-sized genomes at a low cost and with high quality using long and short reads.

RESULTS: We sequenced symbiotic algae Chlorella variabilis using Oxfofrd Nanopore MinION as the long-read sequencer and Illumina HiSeq 4000 as the short-read sequencer and then assembled the genomes under various conditions. Subsequently, we evaluated these assemblies by the gene model quality and RNA-seq mapping rate. We found that long-read only assembly could not be suitable for the comparative genomics studies, but with short reads, we could obtain the acceptable assembly. On the basis of this result, we established the pipeline of de novo assembly for middle-sized algal genome using MinION.

CONCLUSIONS: The genomic change during the early stages of plastid acquisition can now be revealed by sequencing and comparing many algal genomes. Moreover, this pipeline offers a solution for the assembly of various middle-sized eukaryotic genomes with high-quality and ease.}, } @article {pmid30249179, year = {2018}, author = {Stocchi, N and Revuelta, MV and Castronuovo, PAL and Vera, DMA and Ten Have, A}, title = {Molecular dynamics and structure function analysis show that substrate binding and specificity are major forces in the functional diversification of Eqolisins.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {338}, pmid = {30249179}, issn = {1471-2105}, support = {PICT2013-2296//Fondo para la Investigación Científica y Tecnológica/ ; }, mesh = {Amino Acid Sequence ; Amino Acid Substitution/genetics ; Aspartic Acid Endopeptidases/*chemistry/genetics/*metabolism ; Bayes Theorem ; Binding Sites ; Conserved Sequence ; Evolution, Molecular ; Gene Transfer, Horizontal/genetics ; Glycine/chemistry ; Models, Molecular ; *Molecular Dynamics Simulation ; Mutation/genetics ; Phylogeny ; Protein Structure, Secondary ; Sequence Homology, Amino Acid ; Structure-Activity Relationship ; Substrate Specificity ; Thermodynamics ; }, abstract = {BACKGROUND: Eqolisins are rare acid proteases found in archaea, bacteria and fungi. Certain fungi secrete acids as part of their lifestyle and interestingly these also have many eqolisin paralogs, up to nine paralogs have been recorded. This suggests a process of functional redundancy and diversification has occurred, which was the subject of the research we performed and describe here.

RESULTS: We identified eqolisin homologs by means of iterative HMMER analysis of the NR database. The identified sequences were scrutinized for which new hallmarks were identified by molecular dynamics simulations of mutants in highly conserved positions, using the structure of an eqolisin that was crystallized in the presence of a transition state inhibitor. Four conserved glycines were shown to be important for functionality. A substitution of W67F is shown to be accompanied by the L105W substitution. Molecular dynamics shows that the W67 binds to the substrate via a π-π stacking and a salt bridge, the latter being stronger in a virtual W67F/L105W double mutant of the resolved structure of Scytalido-carboxyl peptidase-B (PDB ID: 2IFW). Additional problematic mutations are discussed. Upon sequence scrutiny we obtained a set of 233 sequences that was used to reconstruct a Bayesian phylogenetic tree. We identified 14 putative specificity determining positions (SDPs) of which four are explained by mere structural explanations and nine seem to correspond to functional diversification related with substrate binding and specificity. A first sub-network of SDPs is related to substrate specificity whereas the second sub-network seems to affect the dynamics of three loops that are involved in substrate binding.

CONCLUSION: The eqolisins form a small superfamily of acid proteases with nevertheless many paralogs in acidic fungi. Functional redundancy has resulted in diversification related to substrate specificity and substrate binding.}, } @article {pmid30249176, year = {2018}, author = {Bzhalava, Z and Tampuu, A and Bała, P and Vicente, R and Dillner, J}, title = {Machine Learning for detection of viral sequences in human metagenomic datasets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {336}, pmid = {30249176}, issn = {1471-2105}, support = {PUT1476//Estonian Research Competency Council (EE)/ ; 62721//NordForsk/ ; RB13-0011//Stiftelsen för Strategisk Forskning/ ; }, mesh = {Algorithms ; Base Sequence ; Computational Biology ; *Databases, Genetic ; Humans ; *Machine Learning ; *Metagenomics ; Neural Networks (Computer) ; ROC Curve ; Sequence Analysis, DNA/*methods ; Viruses/classification/*genetics ; }, abstract = {BACKGROUND: Detection of highly divergent or yet unknown viruses from metagenomics sequencing datasets is a major bioinformatics challenge. When human samples are sequenced, a large proportion of assembled contigs are classified as "unknown", as conventional methods find no similarity to known sequences. We wished to explore whether machine learning algorithms using Relative Synonymous Codon Usage frequency (RSCU) could improve the detection of viral sequences in metagenomic sequencing data.

RESULTS: We trained Random Forest and Artificial Neural Network using metagenomic sequences taxonomically classified into virus and non-virus classes. The algorithms achieved accuracies well beyond chance level, with area under ROC curve 0.79. Two codons (TCG and CGC) were found to have a particularly strong discriminative capacity.

CONCLUSION: RSCU-based machine learning techniques applied to metagenomic sequencing data can help identify a large number of putative viral sequences and provide an addition to conventional methods for taxonomic classification.}, } @article {pmid30247705, year = {2018}, author = {Saclier, N and François, CM and Konecny-Dupré, L and Lartillot, N and Guéguen, L and Duret, L and Malard, F and Douady, CJ and Lefébure, T}, title = {Life History Traits Impact the Nuclear Rate of Substitution but Not the Mitochondrial Rate in Isopods.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2900-2912}, doi = {10.1093/molbev/msy184}, pmid = {30247705}, issn = {1537-1719}, abstract = {The rate of molecular evolution varies widely among species. Life history traits (LHTs) have been proposed as a major driver of these variations. However, the relative contribution of each trait is poorly understood. Here, we test the influence of metabolic rate (MR), longevity, and generation time (GT) on the nuclear and mitochondrial synonymous substitution rates using a group of isopod species that have made multiple independent transitions to subterranean environments. Subterranean species have repeatedly evolved a lower MR, a longer lifespan and a longer GT. We assembled the nuclear transcriptomes and the mitochondrial genomes of 13 pairs of closely related isopods, each pair composed of one surface and one subterranean species. We found that subterranean species have a lower rate of nuclear synonymous substitution than surface species whereas the mitochondrial rate remained unchanged. We propose that this decoupling between nuclear and mitochondrial rates comes from different DNA replication processes in these two compartments. In isopods, the nuclear rate is probably tightly controlled by GT alone. In contrast, mitochondrial genomes appear to replicate and mutate at a rate independent of LHTs. These results are incongruent with previous studies, which were mostly devoted to vertebrates. We suggest that this incongruence can be explained by developmental differences between animal clades, with a quiescent period during female gametogenesis in mammals and birds which imposes a nuclear and mitochondrial rate coupling, as opposed to the continuous gametogenesis observed in most arthropods.}, } @article {pmid30247697, year = {2018}, author = {Crognale, S and Venturi, S and Tassi, F and Rossetti, S and Rashed, H and Cabassi, J and Capecchiacci, F and Nisi, B and Vaselli, O and Morrison, HG and Sogin, ML and Fazi, S}, title = {Microbiome profiling in extremely acidic soils affected by hydrothermal fluids: the case of the Solfatara Crater (Campi Flegrei, southern Italy).}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy190}, pmid = {30247697}, issn = {1574-6941}, abstract = {An integrated geochemical and microbiological investigation of soils from the Solfatara Crater (Campi Flegrei, southern Italy) demonstrated that interstitial soil gases dominated by CO2 and other typical hydrothermal gaseous species (e.g. H2S, CH4, ethane, benzene, alkenes and S-bearing organic compounds) influenced the composition of microbial communities. The relatively high concentrations of hydrothermal fluids permeating the soil produced acidic conditions and whitish deposits that characterize the Solfatara Crater floor. Archaea and Bacteria showed almost equal cell abundance (up to 3.2 × 107 and 4.2 × 107 cell/g, respectively) with relatively low levels of biodiversity and equitability in sites characterized by elevated temperatures (up to 70°C), very low pH values (up to 2.2) and reducing conditions. In these sites, high-throughput sequencing showed the marked selection of microorganisms, mainly affiliated with the genera Thermoplasma, Ferroplasma and Acidithiobacillus. A relatively high biodiversity and concomitant distinctive structure of the microbial community were observed in soils poorly affected by fumarolic emissions that were oxic and rich in organic matter.}, } @article {pmid30247672, year = {2018}, author = {Corel, E and Pathmanathan, JS and Watson, AK and Karkar, S and Lopez, P and Bapteste, E}, title = {MultiTwin: A Software Suite to Analyze Evolution at Multiple Levels of Organization Using Multipartite Graphs.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2777-2784}, pmid = {30247672}, issn = {1759-6653}, abstract = {The inclusion of introgressive processes in evolutionary studies induces a less constrained view of evolution. Network-based methods (like large-scale similarity networks) allow to include in comparative genomics all extrachromosomic carriers (like viruses, the most abundant biological entities on the planet) with their cellular hosts. The integration of several levels of biological organization (genes, genomes, communities, environments) enables more comprehensive analyses of gene sharing and improved sequence-based classifications. However, the algorithmic tools for the analysis of such networks are usually restricted to people with high programming skills. We present an integrated suite of software tools named MultiTwin, aimed at the construction, structuring, and analysis of multipartite graphs for evolutionary biology. Typically, this kind of graph is useful for the comparative analysis of the gene content of genomes in microbial communities from the environment and for exploring patterns of gene sharing, for example between distantly related cellular genomes, pangenomes, or between cellular genomes and their mobile genetic elements. We illustrate the use of this tool with an application of the bipartite approach (using gene family-genome graphs) for the analysis of pathogenicity traits in prokaryotes.}, } @article {pmid30247566, year = {2018}, author = {Otte, JM and Blackwell, N and Soos, V and Rughöft, S and Maisch, M and Kappler, A and Kleindienst, S and Schmidt, C}, title = {Sterilization impacts on marine sediment---Are we able to inactivate microorganisms in environmental samples?.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy189}, pmid = {30247566}, issn = {1574-6941}, abstract = {To distinguish between biotic and abiotic processes in laboratory experiments with environmental samples, an effective sterilization method is required that prevents biological activity but does not change physico-geochemical properties of samples. We compared standard sterilization methods with respect to their impact on microbial abundance and activity. We exposed marine sediment to (i) autoclaving, (ii) gamma-radiation or (iii) sodium azide (NaN3) and determined how nucleic acids, microbial productivity, colony forming units (CFUs) and community composition of microorganisms, fungi, unicellular protists and protozoa were affected. In autoclaved and gamma-sterilized sediments, only few colonies formed within 16 days. After addition of NaN3 to the sediment, numerous CFUs (>50) but lower 3H-leucine incorporation rates, i.e. lower protein biosynthesis rates, were found compared to the other two sterilization techniques. Extractable RNA was detected immediately after all sterilization treatments (0.2-17.9 ng/g dry sediment) but decreased substantially by 84%-98% after 16 days of incubation. The total organic carbon content increased from 18 mg L-1 to 220 mg L-1 (autoclaving) and 150 mg L-1 (gamma-radiation) after sterilization. We compare advantages and disadvantages for each tested sterilization method and provide a helpful decision-making resource for choosing the appropriate sterilization technique for environmental studies, particularly for marine sediments.}, } @article {pmid30247565, year = {2018}, author = {Walker, DM and Murray, CM and Talbert, D and Tinker, P and Graham, SP and Crowther, TW}, title = {A salamander's top down effect on fungal communities in a detritivore ecosystem.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy168}, pmid = {30247565}, issn = {1574-6941}, abstract = {The soil decomposer community is a primary driver of carbon cycling in forest ecosystems. Understanding the processes that structure this community is critical to our understanding of the global carbon cycle. In North American forests, soil fungal communities are regulated by grazing soil invertebrates, which are in turn controlled by the predatory red-backed salamander (Plethodon cinereus). The presence of these soil invertebrate taxa is known to exert direct top-down control via selective grazing on saprotrophic fungi, with direct consequences for biogeochemical cycling in soil. We investigated whether the removal of P. cinereus would relieve top-down control on decomposer fungal communities in a tri-trophic mesocosm study. Fungal communities were characterized using metabarcoding and high-throughput DNA sequencing. The β-diversity of fungal communities differed between salamander presence and absence treatments with a strong effect on saprotrophic fungal communities. We concluded that P. cinereus, a mesopredator in the detritivore food chain, exerts a prominent control on the composition and functional diversity of fungal communities in soil through a multi-trophic top-down process. Given their capacity to govern the compositions of soil invertebrates, the activity of these amphibians may be important for regulating ecosystem function and nutrient cycling in temperate forest systems.}, } @article {pmid30247558, year = {2018}, author = {Mix, AK and Cenci, U and Heimerl, T and Marter, P and Wirkner, ML and Moog, D}, title = {Identification and Localization of Peroxisomal Biogenesis Proteins Indicates the Presence of Peroxisomes in the Cryptophyte Guillardia theta and Other "Chromalveolates".}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2834-2852}, pmid = {30247558}, issn = {1759-6653}, abstract = {Peroxisomes are single-membrane-bound organelles with a huge metabolic versatility, including the degradation of fatty acids (β-oxidation) and the detoxification of reactive oxygen species as most conserved functions. Although peroxisomes seem to be present in the majority of investigated eukaryotes, where they are responsible for many eclectic and important spatially separated metabolic reactions, knowledge about their existence in the plethora of protists (eukaryotic microorganisms) is scarce. Here, we investigated genomic data of organisms containing complex plastids with red algal ancestry (so-called "chromalveolates") for the presence of genes encoding peroxins-factors specific for the biogenesis, maintenance, and division of peroxisomes in eukaryotic cells. Our focus was on the cryptophyte Guillardia theta, a marine microalga, which possesses two phylogenetically different nuclei of host and endosymbiont origin, respectively, thus being of enormous evolutionary significance. Besides the identification of a complete set of peroxins in G. theta, we heterologously localized selected factors as GFP fusion proteins via confocal and electron microscopy in the model diatom Phaeodactylum tricornutum. Furthermore, we show that peroxins, and thus most likely peroxisomes, are present in haptophytes as well as eustigmatophytes, brown algae, and alveolates including dinoflagellates, chromerids, and noncoccidian apicomplexans. Our results indicate that diatoms are not the only "chromalveolate" group devoid of the PTS2 receptor Pex7, and thus a PTS2-dependent peroxisomal import pathway, which seems to be absent in haptophytes (Emiliania huxleyi) as well. Moreover, important aspects of peroxisomal biosynthesis and protein import in "chromalveolates"are highlighted.}, } @article {pmid30247544, year = {2018}, author = {Rehan, SM and Glastad, KM and Steffen, MA and Fay, CR and Hunt, BG and Toth, AL}, title = {Conserved Genes Underlie Phenotypic Plasticity in an Incipiently Social Bee.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2749-2758}, pmid = {30247544}, issn = {1759-6653}, abstract = {Despite a strong history of theoretical work on the mechanisms of social evolution, relatively little is known of the molecular genetic changes that accompany transitions from solitary to eusocial forms. Here, we provide the first genome of an incipiently social bee that shows both solitary and social colony organization in sympatry, the Australian carpenter bee Ceratina australensis. Through comparative analysis, we provide support for the role of conserved genes and cis-regulation of gene expression in the phenotypic plasticity observed in nest-sharing, a rudimentary form of sociality. Additionally, we find that these conserved genes are associated with caste differences in advanced eusocial species, suggesting these types of mechanisms could pave the molecular pathway from solitary to eusocial living. Genes associated with social nesting in this species show signatures of being deeply conserved, in contrast to previous studies in other bees showing novel and faster-evolving genes are associated with derived sociality. Our data provide support for the idea that the earliest social transitions are driven by changes in gene regulation of deeply conserved genes.}, } @article {pmid30247121, year = {2018}, author = {Bünger, W and Grönemeyer, JL and Sarkar, A and Reinhold-Hurek, B}, title = {Bradyrhizobium ripae sp. nov., a nitrogen-fixing symbiont isolated from nodules of wild legumes in Namibia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3688-3695}, doi = {10.1099/ijsem.0.002955}, pmid = {30247121}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bradyrhizobium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Intergenic/genetics ; Fabaceae/*microbiology ; Genes, Bacterial ; Multilocus Sequence Typing ; Namibia ; *Nitrogen Fixation ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/*microbiology ; Sequence Analysis, DNA ; Symbiosis ; }, abstract = {Root-nodule bacteria were isolated from wild legumes growing in the Kavango region, Namibia. Using a polyphasic approach, four strains belonging to the genus Bradyrhizobium (WR4T, WR87, T10 and T12) were further characterized to clarify the taxonomic status of this group. On the basis of 16S rRNA gene sequences, the four strains showed highest similarity to Bradyrhizobium elkanii USDA 76T (99.9 %), Bradyrhizobium pachyrhizi PAC48T (identical) and to Bradyrhizobiumbrasilense UFLA03-321T (identical). Multilocus sequence analysis of concatenated glnII-recA-gyrB-dnaK-rpoB sequences and comparison of the intergenic transcribed spacer (ITS) sequences confirmed that the novel group belongs to a distinct lineage of the genus Bradyrhizobium, with <96.7 % (MLSA) and 97.25 % (ITS) nucleotide identity with B. elkanii USDA 76T. Results from the sequence-based analysis were validated by DNA-DNA hybridization experiments and suggested a novel species. Several phenotypic features including carbon compound utilization and growth characteristics supported the phylogenetic data, thus it is concluded that the strains represent a novel species, for which the name Bradyrhizobium ripae sp. nov. is proposed, with type strain WR4T [LMG 30283, DSM 105795, NTCCM 0019 (Windhoek)].}, } @article {pmid30247118, year = {2018}, author = {Han, C and Tian, Y and Zhao, J and Yu, Z and Jiang, S and Guo, X and Xiang, W and Wang, X}, title = {Microbispora triticiradicis sp. nov., a novel actinomycete isolated from the root of wheat (Triticum aestivum L.).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3600-3605}, doi = {10.1099/ijsem.0.003040}, pmid = {30247118}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Triticum/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, designated strain NEAU-HRDPA2-9T, was isolated from the roots of wheat (Triticumaestivum L.) and characterized using a polyphasic approach. The morphological and chemotaxonomic characteristics of the strain coincided with those of members of the genus Microbispora. The 16S rRNA gene sequence analysis showed that the isolate was most closely related to Microbispora bryophytorum NEAU-TX2-2T (98.6 %), Microbispora hainanensis DSM 45428T (98.5 %), Microbispora camponoti 2C-HV3T (98.5 %), Microbispora amethystogenes JCM 3021T (98.2 %), Microbispora siamensis NBRC 104113T (98.1 %), Microbispora corallina JCM 10267T (98.0 %) and Microbispora roseasubsp.rosea JCM 3006T (97.9 %). However, two tree-making algorithms supported the position that strain NEAU-HRDPA2-9T formed a distinct clade with M. siamensis NBRC 104113T and M. hainanensis DSM 45428T. Furthermore, a combination of DNA-DNA hybridization results and some physiological and biochemical properties demonstrated that the strain could be distinguished from its closest relatives. Therefore, it is proposed that strain NEAU-HRDPA2-9T should be classified as representative of a novel species of the genus Microbispora, for which the name Microbisporatriticiradicis sp. nov. is proposed. The type strain is NEAU-HRDPA2-9T (=CGMCC 4.7399T=DSM 104649T).}, } @article {pmid30246498, year = {2018}, author = {DeAngelis, CM and Saul-McBeth, J and Matson, JS}, title = {Vibrio responses to extracytoplasmic stress.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {511-521}, doi = {10.1111/1758-2229.12693}, pmid = {30246498}, issn = {1758-2229}, abstract = {A critical factor for bacterial survival in any environment is the ability to sense and respond appropriately to any stresses encountered. This is especially important for bacteria that inhabit environments that are constantly changing, or for those that inhabit more than one biological niche. Vibrio species are unique in that they are aquatic organisms, and must adapt to ever-changing temperatures, salinity levels and nutrient concentrations. In addition, many species of Vibrio colonize other organisms, and must also deal with components of the host immune response. Vibrio infections of humans and other organisms have become more common in recent years, due to increasing water temperatures in many parts of the world. Therefore, understanding how these ubiquitous marine bacteria adapt to their changing environments is of importance. In this review, we discuss some of the ways that Vibrios sense and respond to the variety of stresses that negatively affect the bacterial cell envelope. Specifically, we will focus on what is currently known about the σE response, the Cpx response and the contributions of OmpU to extracytoplasmic stress relief.}, } @article {pmid30246477, year = {2018}, author = {Lavoie, M and Galí, M and Sévigny, C and Kieber, DJ and Sunda, WG and Spiese, CE and Maps, F and Levasseur, M}, title = {Modelling dimethylsulfide diffusion in the algal external boundary layer: implications for mutualistic and signalling roles.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4157-4169}, doi = {10.1111/1462-2920.14417}, pmid = {30246477}, issn = {1462-2920}, support = {//National Science Foundation/ ; }, abstract = {Dimethylsulfide (DMS), a dominant organic sulfur species in the surface ocean, may act as a signalling molecule and contribute to mutualistic interactions between bacteria and marine algae. These proposed functions depend on the DMS concentration in the vicinity of microorganisms. Here, we modelled the DMS enrichment at the surface of DMS-releasing marine algal cells as a function of DMS production rate, algal cell radius and turbulence. Our results show that the DMS concentration at the surface of unstressed phytoplankton with low DMS production rates can be enriched by <1 nM, whereas for mechanically stressed algae with high activities of the enzyme DMSP-lyase (a coccolithophore and a dinoflagellate) DMS cell surface enrichments can reach ~10 nM, and could potentially reach μM levels in large cells. These DMS enrichments are much higher than the median DMS concentration in the surface ocean (1.9 nM), and thus may attract and support the growth of bacteria living in the phycosphere. The bacteria in turn may provide photoactive iron chelators (siderophores) that enhance algal iron uptake and provide algal growth factors such as auxins and vitamins. The present study highlights new insights on the extent and impact of microscale DMS enrichments at algal surfaces, thereby contributing to our understanding of the potential chemoattractant and mutualistic roles of DMS in marine microorganisms.}, } @article {pmid30246474, year = {2018}, author = {Antunes, J and Leão, P and Vasconcelos, V}, title = {Marine biofilms: diversity of communities and of chemical cues.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12694}, pmid = {30246474}, issn = {1758-2229}, support = {SFRH/BD/99003/2013//Fundação para a Ciência e Tecnologia (FCT)/ ; CVMAR + I (0302_CVMAR_I_1_P)//European Regional Development Fund/ ; NORTE2020//European Regional Development Fund/ ; NORTE-01-0145-FEDER-000035//Innovation and Sustainability in the Management and Exploitation of Marine Resources/ ; UID/Multi/04423/2013//FCT - Foundation for Science and Technology/ ; }, abstract = {Surfaces immersed in seawater are rapidly colonized by various microorganisms, resulting in the formation of heterogenic marine biofilms. These communities are known to influence the settlement of algae spores and invertebrate larvae, triggering a succession of fouling events, with significant environmental and economic impacts. This review covers recent research regarding the differences in composition of biofilms isolated from different artificial surface types and the influence of environmental factors on their formation. One particular phenomenon - bacterial quorum sensing (QS) - allows bacteria to coordinate swarming, biofilm formation among other phenomena. Some other marine biofilm chemical cues are believed to modulate the settlement and the succession of macrofouling organisms, and they are also reviewed here. Finally, since the formation of a marine biofilm is considered to be an initial, QS-dependent step in the development of marine fouling events, QS inhibition is discussed on its potential as a tool for antibiofouling control in marine settings.}, } @article {pmid30246449, year = {2019}, author = {Kolmakova, OV and Gladyshev, MI and Fonvielle, JA and Ganzert, L and Hornick, T and Grossart, HP}, title = {Effects of zooplankton carcasses degradation on freshwater bacterial community composition and implications for carbon cycling.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {34-49}, doi = {10.1111/1462-2920.14418}, pmid = {30246449}, issn = {1462-2920}, support = {//German Academic Exchange Service/ ; //Ministry of Education and Science of the Russian Federation/ ; 57180771//Michail-Lomonosov-Programme-Linie A/ ; NSh-9249.2016.5//President of the Russian Federation/ ; 51.1.1//Russian Federal Tasks of Fundamental Research/ ; 16-54-12048//Russian Foundation for Basic Research/ ; GR1549/23-1//German Science Foundation/ ; GR 1540/29-1//German Science Foundation/ ; }, abstract = {Non-predatory mortality of zooplankton provides an abundant, yet, little studied source of high quality labile organic matter (LOM) in aquatic ecosystems. Using laboratory microcosms, we followed the decomposition of organic carbon of fresh 13 C-labelled Daphnia carcasses by natural bacterioplankton. The experimental setup comprised blank microcosms, that is, artificial lake water without any organic matter additions (B), and microcosms either amended with natural humic matter (H), fresh Daphnia carcasses (D) or both, that is, humic matter and Daphnia carcasses (HD). Most of the carcass carbon was consumed and respired by the bacterial community within 15 days of incubation. A shift in the bacterial community composition shaped by labile carcass carbon and by humic matter was observed. Nevertheless, we did not observe a quantitative change in humic matter degradation by heterotrophic bacteria in the presence of LOM derived from carcasses. However, carcasses were the main factor driving the bacterial community composition suggesting that the presence of large quantities of dead zooplankton might affect the carbon cycling in aquatic ecosystems. Our results imply that organic matter derived from zooplankton carcasses is efficiently remineralized by a highly specific bacterial community, but does not interfere with the bacterial turnover of more refractory humic matter.}, } @article {pmid30246443, year = {2018}, author = {Subalusky, AL and Post, DM}, title = {Context dependency of animal resource subsidies.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12465}, pmid = {30246443}, issn = {1469-185X}, support = {0924393//National Science Foundation/ ; 1343920//National Science Foundation/ ; 1354053//National Science Foundation/ ; 1556848//National Science Foundation/ ; 1753727//National Science Foundation/ ; }, abstract = {The transport of resource subsidies by animals has been documented across a range of species and ecosystems. Although many of these studies have shown that animal resource subsidies can have significant effects on nutrient cycling, ecosystem productivity, and food-web structure, there is a great deal of variability in the occurrence and strength of these effects. Here we propose a conceptual framework for understanding the context dependency of animal resource subsidies, and for developing and testing predictions about the effects of animal subsidies over space and time. We propose a general framework, in which abiotic characteristics and animal vector characteristics from the donor ecosystem interact to determine the quantity, quality, timing, and duration (QQTD) of an animal input. The animal input is translated through the lens of recipient ecosystem characteristics, which include both abiotic and consumer characteristics, to yield the QQTD of the subsidy. The translated subsidy influences recipient ecosystem dynamics through effects on both trophic structure and ecosystem function, which may both influence the recipient ecosystem's response to further inputs and feed back to influence the donor ecosystem. We present a review of research on animal resource subsidies across ecosystem boundaries, placed within the context of this framework, and we discuss how the QQTD of resource subsidies can influence trophic structure and ecosystem function in recipient ecosystems. We explore the importance of understanding context dependency of animal resource subsidies in increasingly altered ecosystems, in which the characteristics of both animal vectors and donor and recipient ecosystems may be changing rapidly. Finally, we make recommendations for future research on animal resource subsidies, and resource subsidies in general, that will increase our understanding and predictive capacity about their ecosystem effects.}, } @article {pmid30246425, year = {2018}, author = {Schrader, M and Jarrett, BJM and Kilner, RM}, title = {Parental care and sibling competition independently increase phenotypic variation among burying beetle siblings.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2546-2552}, pmid = {30246425}, issn = {1558-5646}, support = {//Royal Society/ ; 310785//H2020 European Research Council/ ; }, abstract = {Several recent hypotheses suggest that parental care can influence the extent of phenotypic variation within populations; however, there have been few tests of these ideas. We exploited the facultative nature of posthatching parental care in the burying beetle, Nicrophorus vespilloides, to test whether parental care influences the expression of phenotypic variation in an important fitness trait (body size). We found that parental care and brood size (which influences sibling competition) had positive and independent effects on variation in body size. First, the mean coefficient of variation (CV) of body size was significantly greater in broods that received care than in those that did not. Second, CV body size increased with brood size in both parental care treatments. These results are not consistent with predictions from recent hypotheses that predict parental care will reduce phenotypic variation among siblings. The positive effects of parental care and brood size on phenotypic variation that we observed are likely due to sibling competition for access to provisioning parents and competition for limiting resources contained in the breeding carcass. Our results suggest that future theory linking parental care to the generation and maintenance of phenotypic variation must integrate the nature of interactions among family members.}, } @article {pmid30246424, year = {2018}, author = {Chen, J and Robb, CS and Unfried, F and Kappelmann, L and Markert, S and Song, T and Harder, J and Avcı, B and Becher, D and Xie, P and Amann, RI and Hehemann, JH and Schweder, T and Teeling, H}, title = {Alpha- and beta-mannan utilization by marine Bacteroidetes.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4127-4140}, doi = {10.1111/1462-2920.14414}, pmid = {30246424}, issn = {1462-2920}, support = {//Office of Science/ ; DE-AC02-05CH11231//U.S. Department of Energy/ ; //Chinese Academy of Sciences/ ; HE 7217/1-1//German Research Foundation/ ; }, abstract = {Marine microscopic algae carry out about half of the global carbon dioxide fixation into organic matter. They provide organic substrates for marine microbes such as members of the Bacteroidetes that degrade algal polysaccharides using carbohydrate-active enzymes (CAZymes). In Bacteroidetes genomes CAZyme encoding genes are mostly grouped in distinct regions termed polysaccharide utilization loci (PULs). While some studies have shown involvement of PULs in the degradation of algal polysaccharides, the specific substrates are for the most part still unknown. We investigated four marine Bacteroidetes isolated from the southern North Sea that harbour putative mannan-specific PULs. These PULs are similarly organized as PULs in human gut Bacteroides that digest α- and β-mannans from yeasts and plants respectively. Using proteomics and defined growth experiments with polysaccharides as sole carbon sources we could show that the investigated marine Bacteroidetes express the predicted functional proteins required for α- and β-mannan degradation. Our data suggest that algal mannans play an as yet unknown important role in the marine carbon cycle, and that biochemical principles established for gut or terrestrial microbes also apply to marine bacteria, even though their PULs are evolutionarily distant.}, } @article {pmid30246414, year = {2018}, author = {Duret, MT and Lampitt, RS and Lam, P}, title = {Prokaryotic niche partitioning between suspended and sinking marine particles.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12692}, pmid = {30246414}, issn = {1758-2229}, abstract = {Suspended particles are major organic carbon substrates for heterotrophic microorganisms in the mesopelagic ocean (100-1000 m). Nonetheless, communities associated with these particles have been overlooked compared with sinking particles, the latter generally considered as main carbon transporters to the deep ocean. This study is the first to differentiate prokaryotic communities associated with suspended and sinking particles, collected with a marine snow catcher at four environmentally distinct stations in the Scotia Sea. Amplicon sequencing of 16S rRNA gene revealed distinct prokaryotic communities associated with the two particle-types in the mixed-layer (0-100 m) and upper-mesopelagic zone (mean dissimilarity 42.5% ± 15.2%). Although common remineralising taxa were present within both particle-types, gammaproteobacterial Pseudomonadales and Vibrionales, and alphaproteobacterial Rhodobacterales were found enriched in sinking particles up to 32-fold, while Flavobacteriales (Bacteroidetes) favoured suspended particles. We propose that this niche-partitioning may be driven by organic matter properties found within both particle-types: K-strategists, specialised in the degradation of complex organic compounds, thrived on semi-labile suspended particles, while generalists r-strategists were adapted to the transient labile organic contents of sinking particles. Differences between the two particle-associated communities were more pronounced in the mesopelagic than in the surface ocean, likely resulting from exchanges between particle-pools enabled by the stronger turbulence.}, } @article {pmid30246403, year = {2018}, author = {Ruhl, IA and Grasby, SE and Haupt, ES and Dunfield, PF}, title = {Analysis of microbial communities in natural halite springs reveals a domain-dependent relationship of species diversity to osmotic stress.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {695-703}, doi = {10.1111/1758-2229.12695}, pmid = {30246403}, issn = {1758-2229}, abstract = {Microbial species diversity may peak at certain optimal environmental conditions and decrease toward more extreme conditions. Indeed, bell-shaped relationships of species diversity against pH and temperature have been demonstrated, but diversity patterns across other environmental conditions are less well reported. In this study, we investigated the impact of salinity on the diversity of microorganisms from all three domains in a large set of natural springs with salinities ranging from freshwater to halite saturated. Habitat salinity was found to be linearly and inversely related to diversity of all three domains. The relationship was strongest in the bacteria, where salinity explained up to 44% of the variation in different diversity metrics (OTUs, Shannon index, and Phylogenetic Diversity). However, the relationship was weaker for Eukarya and Archaea. The known salt-in strategist Archaea of the Halobacteriaceae even showed the opposite trend, with increasing diversity at higher salinity. We propose that high energetic requirements constrain species diversity at high salinity but that the diversity of taxa with energetically less expensive osmotolerance strategies is less affected. Declining diversity with increasing osmotic stress may be a general rule for microbes as well as plants and animals, but the strength of this relationship varies greatly across microbial taxa.}, } @article {pmid30246402, year = {2018}, author = {Daly, P and López, SC and Peng, M and Lancefield, CS and Purvine, SO and Kim, YM and Zink, EM and Dohnalkova, A and Singan, VR and Lipzen, A and Dilworth, D and Wang, M and Ng, V and Robinson, E and Orr, G and Baker, SE and Bruijnincx, PCA and Hildén, KS and Grigoriev, IV and Mäkelä, MR and de Vries, RP}, title = {Dichomitus squalens partially tailors its molecular responses to the composition of solid wood.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4141-4156}, doi = {10.1111/1462-2920.14416}, pmid = {30246402}, issn = {1462-2920}, support = {824.15.023//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; 308284//Academy of Finland/ ; DE-AC02-05CH11231//Office of Science of the U.S. Department of Energy/ ; //Catchbio/ ; }, abstract = {White-rot fungi, such as Dichomitus squalens, degrade all wood components and inhabit mixed-wood forests containing both soft- and hardwood species. In this study, we evaluated how D. squalens responded to the compositional differences in softwood [guaiacyl (G) lignin and higher mannan content] and hardwood [syringyl/guaiacyl (S/G) lignin and higher xylan content] using semi-natural solid cultures. Spruce (softwood) and birch (hardwood) sticks were degraded by D. squalens as measured by oxidation of the lignins using 2D-NMR. The fungal response as measured by transcriptomics, proteomics and enzyme activities showed a partial tailoring to wood composition. Mannanolytic transcripts and proteins were more abundant in spruce cultures, while a proportionally higher xylanolytic activity was detected in birch cultures. Both wood types induced manganese peroxidases to a much higher level than laccases, but higher transcript and protein levels of the manganese peroxidases were observed on the G-lignin rich spruce. Overall, the molecular responses demonstrated a stronger adaptation to the spruce rather than birch composition, possibly because D. squalens is mainly found degrading softwoods in nature, which supports the ability of the solid wood cultures to reflect the natural environment.}, } @article {pmid30246365, year = {2018}, author = {Murakami, T and Segawa, T and Takeuchi, N and Barcaza Sepúlveda, G and Labarca, P and Kohshima, S and Hongoh, Y}, title = {Metagenomic analyses highlight the symbiotic association between the glacier stonefly Andiperla willinki and its bacterial gut community.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4170-4183}, doi = {10.1111/1462-2920.14420}, pmid = {30246365}, issn = {1462-2920}, support = {16H04840//Japan Society for the Promotion of Science/ ; 17K19423//Japan Society for the Promotion of Science/ ; 22241005//Japan Society for the Promotion of Science/ ; 23117003//Japan Society for the Promotion of Science/ ; 26241020//Japan Society for the Promotion of Science/ ; GS009//NEXT/ ; }, abstract = {The glacier stonefly Andiperla willinki is the largest metazoan inhabiting the Patagonian glaciers. In this study, we analysed the gut microbiome of the aquatic nymphs by 16S rRNA gene amplicon and metagenomic sequencing. The bacterial gut community was consistently dominated by taxa typical of animal digestive tracts, such as Dysgonomonadaceae and Lachnospiraceae, as well as those generally indigenous to glacier environments, such as Polaromonas. Interestingly, the dominant Polaromonas phylotypes detected in the stonefly gut were almost never detected in the glacier surface habitat. Fluorescence in situ hybridization analysis revealed that the bacterial lineages typical of animal guts colonized the gut wall in a co-aggregated form, while Polaromonas cells were not included in the aggregates. Draft genomes of several dominant bacterial lineages were reconstructed from metagenomic datasets and indicated that the predominant Dysgonomonadaceae bacterium is capable of degrading various polysaccharides derived from host-ingested food, such as algae, and that other dominant bacterial lineages ferment saccharides liberated by the polysaccharide degradation. Our results suggest that the gut bacteria-host association in the glacier stonefly contributes to host nutrition as well as material cycles in the glacier environment.}, } @article {pmid30246324, year = {2019}, author = {Thomas, PJ and Boller, AJ and Satagopan, S and Tabita, FR and Cavanaugh, CM and Scott, KM}, title = {Isotope discrimination by form IC RubisCO from Ralstonia eutropha and Rhodobacter sphaeroides, metabolically versatile members of 'Proteobacteria' from aquatic and soil habitats.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {72-80}, doi = {10.1111/1462-2920.14423}, pmid = {30246324}, issn = {1462-2920}, support = {BIO-OCE 0327488//National Science Foundation/ ; IOS-1257532//National Science Foundation/ ; GM95742//National Institutes of Health/ ; }, abstract = {RubisCO, the CO2 fixing enzyme of the Calvin-Benson-Bassham (CBB) cycle, is responsible for the majority of carbon fixation on Earth. RubisCO fixes 12 CO2 faster than 13 CO2 resulting in 13 C-depleted biomass, enabling the use of δ13 C values to trace CBB activity in contemporary and ancient environments. Enzymatic fractionation is expressed as an ε value, and is routinely used in modelling, for example, the global carbon cycle and climate change, and for interpreting trophic interactions. Although values for spinach RubisCO (ε = ~29‰) have routinely been used in such efforts, there are five different forms of RubisCO utilized by diverse photolithoautotrophs and chemolithoautotrophs and ε values, now known for four forms (IA, B, D and II), vary substantially with ε = 11‰ to 27‰. Given the importance of ε values in δ13 C evaluation, we measured enzymatic fractionation of the fifth form, form IC RubisCO, which is found widely in aquatic and terrestrial environments. Values were determined for two model organisms, the 'Proteobacteria' Ralstonia eutropha (ε = 19.0‰) and Rhodobacter sphaeroides (ε = 22.4‰). It is apparent from these measurements that all RubisCO forms measured to date discriminate less than commonly assumed based on spinach, and that enzyme ε values must be considered when interpreting and modelling variability of δ13 C values in nature.}, } @article {pmid30246285, year = {2018}, author = {Lenz, TL and Hafer, N and Samonte, IE and Yeates, SE and Milinski, M}, title = {Cryptic haplotype-specific gamete selection yields offspring with optimal MHC immune genes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2478-2490}, pmid = {30246285}, issn = {1558-5646}, support = {LE 2593/3-1//Deutsche Forschungsgemeinschaft/ ; //Max-Planck-Gesellschaft/ ; }, abstract = {Females choose specific mates in order to produce fitter offspring. However, several factors interfere with females' control over fertilization of their eggs, including sneaker males and phenotypically unpredictable allele segregation during meiosis. Mate choice at the individual level thus provides only a poor approximation for obtaining the best genetic match. Consequently, postcopulatory sperm selection by female oocytes has been proposed as a mechanism to achieve complementary combinations of parental haplotypes. Here, using controlled in vitro fertilization of three-spined stickleback eggs, we find haplotype-specific fertilization bias toward gametes with complementary major histocompatibility complex (MHC) immunogenes. The resulting zygote (and thus offspring) genotypes exhibit an intermediate level of individual MHC diversity that was previously shown to confer highest pathogen resistance. Our finding of haplotype-specific gamete selection thus represents an intriguing mechanism for fine-tuned optimization of the offspring's immune gene composition and an evolutionary advantage in the Red Queen dynamics of host-parasite coevolution.}, } @article {pmid30246284, year = {2018}, author = {Qian, B and Liu, X and Jia, J and Cai, Y and Chen, C and Zhang, H and Zheng, X and Wang, P and Zhang, Z}, title = {MoPpe1 partners with MoSap1 to mediate TOR and cell wall integrity signalling in growth and pathogenicity of the rice blast fungus Magnaporthe oryzae.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3964-3979}, doi = {10.1111/1462-2920.14421}, pmid = {30246284}, issn = {1462-2920}, support = {//Innovation Team Program for Jiangsu Universities/ ; AI121460//Foundation for the National Institutes of Health/ ; AI121451//Foundation for the National Institutes of Health/ ; 31530063//National Natural Science Foundation of China/ ; 31470248//National Natural Science Foundation of China/ ; KYTZ201604//The Fundamental Research Funds for the Central Universities/ ; }, abstract = {In the rice blast fungus Magnaporthe oryzae, the cell wall integrity (CWI) signalling pathway governs cell wall changes in response to external cues and normal CWI signalling is critical for appressorium function and pathogenicity. We previously characterized the mitogen-activated protein kinase (MAPK) kinase MoMkk1 as an integral component of the CWI pathway. Using the affinity purification approach, we have identified MoMkk1-interacting MoPpe1 as a homologue of Saccharomyces cerevisiae serine/threonine protein phosphatase Sit4/Ppe1. We found that MoPpe1 is required for vegetative growth, conidiation and full virulence. In addition, we found that MoPpe1 interacts with MoSap1, a protein with functions similar to MoPpe1. Intriguingly, we found that MoPpe1-MoSap1 interaction is related to CWI and target of rapamycin (TOR) pathways. We presented evidence suggesting that MoPpe1 and MoSap1 function as an adaptor complex linking CWI and TOR signalling and that the activation of the TOR pathway leads to suppression of CWI signalling, resulting in defects in appressorium function and pathogenicity. Taken together, our studies not only reveal important functions of MoMkk1-MoPpe1-MoSap1 interactions in growth and pathogenicity of the blast fungus, but also highlight the complexity of regulatory networks involving conserved yet novel regulatory mechanisms of CWI and TOR signalling.}, } @article {pmid30246283, year = {2019}, author = {Ramazzotti, M and Stefanini, I and Di Paola, M and De Filippo, C and Rizzetto, L and Berná, L and Dapporto, L and Rivero, D and Tocci, N and Weil, T and Lenucci, MS and Lionetti, P and Cavalieri, D}, title = {Population genomics reveals evolution and variation of Saccharomyces cerevisiae in the human and insects gut.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {50-71}, doi = {10.1111/1462-2920.14422}, pmid = {30246283}, issn = {1462-2920}, support = {//Amici onlus associazione, malattie infiammatorie croniche intestinali/ ; Grant 0875//Ente Cassa di Risparmio di Firenze/ ; Progetto giovani si, POR FSE 2014-2020, "VESPATE//Regione Toscana/ ; Progetto "NUTRA-TOSCAFRICA" (No.50)//Regione Toscana/ ; HEALTH-2010-242220//Seventh Framework Programme [FP7/2007-2013]/ ; }, abstract = {The quest to discover the variety of ecological niches inhabited by Saccharomyces cerevisiae has led to research in areas as diverse as wineries, oak trees and insect guts. The discovery of fungal communities in the human gastrointestinal tract suggested the host's gut as a potential reservoir for yeast adaptation. Here, we report the existence of yeast populations associated with the human gut (HG) that differ from those isolated from other human body sites. Phylogenetic analysis on 12 microsatellite loci and 1715 combined CDSs from whole-genome sequencing revealed three subclusters of HG strains with further evidence of clonal colonization within the host's gut. The presence of such subclusters was supported by other genomic features, such as copy number variation, absence/introgressions of CDSs and relative polymorphism frequency. Functional analysis of CDSs specific of the different subclusters suggested possible alterations in cell wall composition and sporulation features. The phenotypic analysis combined with immunological profiling of these strains further showed that sporulation was related with strain-specific genomic characteristics in the immune recognition pattern. We conclude that both genetic and environmental factors involved in cell wall remodelling and sporulation are the main drivers of adaptation in S. cerevisiae populations in the human gut.}, } @article {pmid30246282, year = {2018}, author = {Aristide, L and Bastide, P and Dos Reis, SF and Pires Dos Santos, TM and Lopes, RT and Perez, SI}, title = {Multiple factors behind early diversification of skull morphology in the continental radiation of New World monkeys.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2697-2711}, doi = {10.1111/evo.13609}, pmid = {30246282}, issn = {1558-5646}, support = {2017/10583-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 206298/Z/17/Z//Welcome Trust Collaborative Award/ ; 2014-1810//Fondo para la Investigación Científica y Tecnológica/ ; 2015e2018//Fondo para la Investigación Científica y Tecnológica/ ; }, abstract = {Understanding the origin of diversity is a fundamental problem in evolutionary biology. The null expectation for the evolutionary diversification is that all changes in biological diversity are the result of random processes. Adaptive radiations depart from this expectation as ecological factors and natural selection are supposed to play a central role in driving exceptional diversification. However, it is not well understood how large-scale continental radiations, given their characteristics, fit to these opposing theoretical models. Here, we used phylogenetic comparative methods and geometric morphometrics to study the evolutionary process of cranial diversification in the continental radiation of New World monkeys. Particularly, we tested several alternative evolutionary scenarios for morphological evolution in the clade. Results indicated that despite the platyrrhine radiation being old and geographically widespread, the formative patterns arising from the initial stages of diversification probably associated with an adaptive radiation can still be recognized today. We also show that no single explored factor (e.g., ecological or allometric) can be invoked as a complete explanation for the observed phenotypic diversity patterns in the clade and, moreover, that different cranial regions exhibit particular macroevolutionary patterns. Together, our results highlight the evident complexity behind large-scale evolutionary radiations.}, } @article {pmid30246245, year = {2018}, author = {Felice, RN and Randau, M and Goswami, A}, title = {A fly in a tube: Macroevolutionary expectations for integrated phenotypes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2580-2594}, doi = {10.1111/evo.13608}, pmid = {30246245}, issn = {1558-5646}, support = {STG-2014-637171//ERC/ ; RPG 2013-124//Leverhulme Trust/ ; FR-TAF-5635//SYNTHESIS/ ; }, abstract = {Phenotypic integration and modularity are ubiquitous features of complex organisms, describing the magnitude and pattern of relationships among biological traits. A key prediction is that these relationships, reflecting genetic, developmental, and functional interactions, shape evolutionary processes by governing evolvability and constraint. Over the last 60 years, a rich literature of research has quantified patterns of integration and modularity across a variety of clades and systems. Only recently has it become possible to contextualize these findings in a phylogenetic framework to understand how trait integration interacts with evolutionary tempo and mode. Here, we review the state of macroevolutionary studies of integration and modularity, synthesizing empirical and theoretical work into a conceptual framework for predicting the effects of integration on evolutionary rate and disparity: a fly in a tube. While magnitude of integration is expected to influence the potential for phenotypic variation to be produced and maintained, thus defining the shape and size of a tube in morphospace, evolutionary rate, or the speed at which a fly moves around the tube, is not necessarily controlled by trait interactions. Finally, we demonstrate this reduced disparity relative to the Brownian expectation for a given rate of evolution with an empirical example: the avian cranium.}, } @article {pmid30246244, year = {2018}, author = {Jones, KS and Weisrock, DW}, title = {Genomic data reject the hypothesis of sympatric ecological speciation in a clade of Desmognathus salamanders.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2378-2393}, doi = {10.1111/evo.13606}, pmid = {30246244}, issn = {1558-5646}, support = {//University of Kentucky/ ; 135500//Division of Environmental Biology/ ; //Kentucky Academy of Science/ ; //Society of Systematic Biologists/ ; }, abstract = {Closely related taxa with dissimilar morphologies are often considered to have diverged via natural selection favoring different phenotypes. However, some studies have found these scenarios to be paired with limited or no genetic differentiation. Desmognathus quadramaculatus and D. marmoratus are sympatric salamander species thought to represent a case of ecological speciation based on distinct morphologies, but the results of previous studies have not resolved corresponding patterns of lineage divergence. Here, we use genome-wide data to test this hypothesis of ecological speciation. Population structure analyses partitioned individuals geographically, but not morphologically, into two adjacent regions of western North Carolina: Pisgah and Nantahala. Phylogenetic analyses confirmed the nominal species are nonmonophyletic and resolved deep divergence between the two geographic clusters. Model-testing overwhelmingly supported the hypothesis that lineage divergence followed geography. Finally, ecological niche modeling showed that Pisgah and Nantahala individuals occupy different climatic niches, and geographic boundaries for the two lineages correspond to differences in precipitation regimes across southern Appalachia. Overall, we reject the previous hypothesis of ecological speciation based on microhabitat partitioning. Instead, our results suggest that there are two cryptic lineages, each containing the same pair of morphotypes.}, } @article {pmid30245567, year = {2018}, author = {Kalesinskas, L and Cudone, E and Fofanov, Y and Putonti, C}, title = {S-plot2: Rapid Visual and Statistical Analysis of Genomic Sequences.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318797354}, pmid = {30245567}, issn = {1176-9343}, abstract = {With the daily release of data from whole genome sequencing projects, tools to facilitate comparative studies are hard-pressed to keep pace. Graphical software solutions can readily recognize synteny by measuring similarities between sequences. Nevertheless, regions of dissimilarity can prove to be equally informative; these regions may harbor genes acquired via lateral gene transfer (LGT), signify gene loss or gain, or include coding regions under strong selection. Previously, we developed the software S-plot. This tool employed an alignment-free approach for comparing bacterial genomes and generated a heatmap representing the genomes' similarities and dissimilarities in nucleotide usage. In prior studies, this tool proved valuable in identifying genome rearrangements as well as exogenous sequences acquired via LGT in several bacterial species. Herein, we present the next generation of this tool, S-plot2. Similar to its predecessor, S-plot2 creates an interactive, 2-dimensional heatmap capturing the similarities and dissimilarities in nucleotide usage between genomic sequences (partial or complete). This new version, however, includes additional metrics for analysis, new reporting options, and integrated BLAST query functionality for the user to interrogate regions of interest. Furthermore, S-plot2 can evaluate larger sequences, including whole eukaryotic chromosomes. To illustrate some of the applications of the tool, 2 case studies are presented. The first examines strain-specific variation across the Pseudomonas aeruginosa genome and strain-specific LGT events. In the second case study, corresponding human, chimpanzee, and rhesus macaque autosomes were studied and lineage specific contributions to divergence were estimated. S-plot2 provides a means to both visually and quantitatively compare nucleotide sequences, from microbial genomes to eukaryotic chromosomes. The case studies presented illustrate just 2 potential applications of the tool, highlighting its capability to identify and investigate the variation in molecular divergence rates across sequences. S-plot2 is freely available through https://bitbucket.org/lkalesinskas/splot and is supported on the Linux and MS Windows operating systems.}, } @article {pmid30245075, year = {2018}, author = {Hays, GC and Doyle, TK and Houghton, JDR}, title = {A Paradigm Shift in the Trophic Importance of Jellyfish?.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {874-884}, doi = {10.1016/j.tree.2018.09.001}, pmid = {30245075}, issn = {1872-8383}, abstract = {The past 30 years have seen several paradigm shifts in our understanding of how ocean ecosystems function. Now recent technological advances add to an overwhelming body of evidence for another paradigm shift in terms of the role of gelatinous plankton (jellyfish) in marine food webs. Traditionally viewed as trophic dead ends, stable isotope analysis of predator tissues, animal-borne cameras, and DNA analysis of fecal and gut samples (metabarcoding) are all indicating that many taxa routinely consume jellyfish. Despite their low energy density, the contribution of jellyfish to the energy budgets of predators may be much greater than assumed because of rapid digestion, low capture costs, availability, and selective feeding on the more energy-rich components. Feeding on jellyfish may make marine predators susceptible to ingestion of plastics.}, } @article {pmid30244670, year = {2018}, author = {Koonin, EV}, title = {Open questions: CRISPR biology.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {95}, pmid = {30244670}, issn = {1741-7007}, abstract = {CRISPR-Cas systems, the purveyors of adaptive immunity in archaea and bacteria and sources of the new generation of genome engineering tools, have been studied in exquisite molecular detail. However, when it comes to biological functions, ecology, and evolution of CRISPR-Cas, many more intriguing questions remain than there are answers.}, } @article {pmid30244151, year = {2019}, author = {Schön, I and Kamiya, T and Van den Berghe, T and Van den Broecke, L and Martens, K}, title = {Novel Cardinium strains in non-marine ostracod (Crustacea) hosts from natural populations.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {406-415}, doi = {10.1016/j.ympev.2018.09.008}, pmid = {30244151}, issn = {1095-9513}, abstract = {Endosymbiotic bacteria are known from many metazoan taxa, where they manipulate host biology and reproduction. Here, we used classic PCR amplification and direct DNA sequencing with universal primers for four different endosymbionts to test for their presence in more than 300 specimens of three recent non-marine ostracod superfamilies from different geographic areas and aquatic habitats. We verified these results with "high throughput" amplicon sequencing of 16S of nine selected specimens and evolutionary placement algorithms. The phylogenetic position of endosymbionts detected in ostracod hosts was compared to known endosymbionts from other metazoans. While Wolbachia, Spiroplasma and Rickettsia are absent, we find evidence for the general presence of Cardinium bacteria in natural populations of various non-marine ostracod species. Phylogenetic reconstructions based on Cardinium 16S data and estimates of genetic distances both indicate that Cardinium from ostracods are distantly related to Cardinium from Diptera and Nematoda but represent novel strains with a monophyletic origin. Cardinium bacteria from different ostracod hosts have genetic distances of up to 3.8%, providing evidence against recent and frequent horizontal transmissions amongst the three ostracod superfamilies. High throughput sequencing reveals more than 400 different 16S amplicon sequence variants in the investigated ostracods as well as the presence of different Cardinium strains within individual Eucypris virens and Heterocypris hosts. These results call for future, more in-depth investigations. Mapping Cardinium infections on COI trees of non-marine ostracod hosts shows that the occurrence of these endosymbionts is not linked to genetic species identity or phylogenetic host groups and, except for one ostracod morphospecies, prevalence never reaches 100%.}, } @article {pmid30243834, year = {2018}, author = {Doherty, TS and Bland, LM and Bryan, BA and Neale, T and Nicholson, E and Ritchie, EG and Driscoll, DA}, title = {Expanding the Role of Targets in Conservation Policy.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {809-812}, doi = {10.1016/j.tree.2018.08.014}, pmid = {30243834}, issn = {1872-8383}, abstract = {Conservation targets perform beneficial auxiliary functions that are rarely acknowledged, including raising awareness, building partnerships, promoting investment, and developing new knowledge. Building on these auxiliary functions could enable more rapid progress towards current targets and inform the design of future targets.}, } @article {pmid30243673, year = {2018}, author = {Mahato, S and Nie, J and Plachetzki, DC and Zelhof, AC}, title = {A mosaic of independent innovations involving eyes shut are critical for the evolutionary transition from fused to open rhabdoms.}, journal = {Developmental biology}, volume = {443}, number = {2}, pages = {188-202}, doi = {10.1016/j.ydbio.2018.09.016}, pmid = {30243673}, issn = {1095-564X}, mesh = {Animals ; Arthropods/metabolism ; Biological Evolution ; Compound Eye, Arthropod/*embryology/metabolism/physiology ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/embryology/metabolism ; Evolution, Molecular ; Eye Proteins/*genetics/metabolism ; Open Reading Frames/genetics ; Photoreceptor Cells/metabolism/*physiology ; Phylogeny ; Tribolium/embryology/metabolism ; }, abstract = {A fundamental question in evolutionary biology is how developmental processes are modified to produce morphological innovations while abiding by functional constraints. Here we address this question by investigating the cellular mechanism responsible for the transition between fused and open rhabdoms in ommatidia of apposition compound eyes; a critical step required for the development of visual systems based on neural superposition. Utilizing Drosophila and Tribolium as representatives of fused and open rhabdom morphology in holometabolous insects respectively, we identified three changes required for this innovation to occur. First, the expression pattern of the extracellular matrix protein Eyes Shut (EYS) was co-opted and expanded from mechanosensory neurons to photoreceptor cells in taxa with open rhabdoms. Second, EYS homologs obtained a novel extension of the amino terminus leading to the internalization of a cleaved signal sequence. This amino terminus extension does not interfere with cleavage or function in mechanosensory neurons, but it does permit specific targeting of the EYS protein to the apical photoreceptor membrane. Finally, a specific interaction evolved between EYS and a subset of Prominin homologs that is required for the development of open, but not fused, rhabdoms. Together, our findings portray a case study wherein the evolution of a set of molecular novelties has precipitated the origin of an adaptive photoreceptor cell arrangement.}, } @article {pmid30243593, year = {2018}, author = {Timmermans, S and Libert, C}, title = {Easy Access to and Applications of the Sequences of All Protein-Coding Genes of All Sequenced Mouse Strains.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {12}, pages = {899-902}, doi = {10.1016/j.tig.2018.08.007}, pmid = {30243593}, issn = {0168-9525}, abstract = {An easily accessible and searchable overview of all protein sequences in the 36 genome-sequenced mouse strains, compared to those in the reference strain C57BL/6J, is now available, as well as an overview of the aberrant proteins in this reference strain. We provide an insight into the advantages of using these databases.}, } @article {pmid30243514, year = {2019}, author = {Davis, KM and Isberg, RR}, title = {One for All, but Not All for One: Social Behavior during Bacterial Diseases.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {64-74}, doi = {10.1016/j.tim.2018.09.001}, pmid = {30243514}, issn = {1878-4380}, support = {R01 AI110684/AI/NIAID NIH HHS/United States ; }, abstract = {It has been known for decades that individual cells within pathogenic bacterial populations have reduced antibiotic susceptibility, which is linked to decreased metabolic rates. A similar phenomenon occurs with virulence-associated proteins, as reduced expression is associated with increased fitness of individual cells. Non-producers within the population can benefit from the virulence proteins produced by others in the population without suffering a fitness cost, thus maintaining a genetically uniform population. Cooperative behavior has been reported for Salmonella and Yersinia, consistent with selection of social behavior to retain genes associated with pathogenesis; however, cooperation was unclear within Mycobacterium populations. This review focuses on these recent descriptions of cooperation, discusses the mechanisms driving heterogeneity, and evaluates the evidence that expression of virulence-associated proteins comes at a fitness cost.}, } @article {pmid30242943, year = {2018}, author = {McNutt, EJ and Zipfel, B and DeSilva, JM}, title = {The evolution of the human foot.}, journal = {Evolutionary anthropology}, volume = {27}, number = {5}, pages = {197-217}, doi = {10.1002/evan.21713}, pmid = {30242943}, issn = {1520-6505}, support = {(IFR13022117561)//National Research Foundation/ ; (AOP15092914)//National Research Foundation African Origins Platform/ ; //Dartmouth College/ ; //Leakey Foundation/ ; //University of the Witwatersrand/ ; }, mesh = {Animals ; Anthropology, Physical ; *Biological Evolution ; Foot/*anatomy & histology/*physiology ; Fossils ; Hominidae ; Humans ; Walking/*physiology ; }, abstract = {There are 26 bones in each foot (52 in total), meaning that roughly a quarter of the human skeleton consists of foot bones. Yet, early hominin foot fossils are frustratingly rare, making it quite difficult to reconstruct the evolutionary history of the human foot. Despite the continued paucity of hominid or hominin foot fossils from the late Miocene and early Pliocene, the last decade has witnessed the discovery of an extraordinary number of early hominin foot bones, inviting a reassessment of how the human foot evolved, and providing fresh new evidence for locomotor diversity throughout hominin evolution. Here, we provide a review of our current understanding of the evolutionary history of the hominin foot.}, } @article {pmid30242940, year = {2018}, author = {Grüter, C}, title = {Repeated switches from cooperative to selfish worker oviposition during stingless bee evolution.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1843-1851}, doi = {10.1111/jeb.13377}, pmid = {30242940}, issn = {1420-9101}, abstract = {Reproductive division of labour is a defining feature of insect societies. Stingless bees (Meliponini) are an interesting exception among the highly eusocial insects in that workers of many species contribute significantly to the production of males. Since workers remain sterile in other species of this large tropical tribe, it has been hypothesized that, in the latter species, ancestral queens have won the conflict over who produces the males. The fact that sterile workers of some species lay trophic eggs to feed the queen and display ritualized behaviours towards her during oviposition has been interpreted as an evolutionary relic of this ancient conflict. Here, I used ancestral state estimation to test whether worker reproduction is indeed the ancestral condition and worker sterility a derived state in stingless bees. Contrary to this hypothesis, data suggest that trophic egg laying was the ancestral condition, whereas selfish worker reproduction in queenright colonies evolved subsequently during stingless bee diversification. The appearance of worker reproduction in queenright conditions was tightly linked to the laying of trophic eggs, which suggests that having activated ovaries in queen presence facilitates the evolution of worker reproduction. Worker reproduction is also linked to brood cell architecture, but surprisingly not to colony size or queen-worker dimorphism. The reason for this association between brood cell architecture and worker oviposition is currently unknown. These results suggest that trophic eggs are not a relic of an ancient conflict, but a sign of overlapping interests between the queen and workers about who produces the males.}, } @article {pmid30242472, year = {2018}, author = {Joshi, G and Chauhan, C and Das, S}, title = {Microsynteny analysis to understand evolution and impact of polyploidization on MIR319 family within Brassicaceae.}, journal = {Development genes and evolution}, volume = {228}, number = {6}, pages = {227-242}, pmid = {30242472}, issn = {1432-041X}, support = {BT/PR14532/AGR/36/673/2010//Department of Biotechnology , Ministry of Science and Technology/ ; JRF/SRF//Department of Biotechnology , Ministry of Science and Technology/ ; JRF/SRF//University Grants Commission/ ; R&D Grants//University of Delhi/ ; }, abstract = {The availability of a large number of whole-genome sequences allows comparative genomic analysis to reveal and understand evolution of regulatory regions and elements. The role played by events such as whole-genome and segmental duplications followed by genome fractionation in shaping genomic landscape and in expansion of gene families is crucial toward developing insights into evolutionary trends and consequences such as sequence and functional diversification. Members of Brassicaceae are known to have experienced several rounds of whole-genome duplication (WGD) that have been termed as paleopolyploidy, mesopolyploidy, and neopolyploidy. Such repeated events led to the creation and expansion of a large number of gene families. MIR319 is reported to be one of the most ancient and conserved plant MIRNA families and plays a role in growth and development including leaf development, seedling development, and embryo patterning. We have previously reported functional diversification of members of miR319 in Brassica oleracea affecting leaf architecture; however, the evolutionary history of the MIR319 gene family across Brassicaceae remains unknown and requires investigation. We therefore identified homologous and homeologous segments of ca. 100 kb, with or without MIR319, performed comparative synteny analysis and genome fractionation studies. We detected variable rates of gene retention across members of Brassicaceae when genomic blocks of MIR319a, MIR319b, and MIR319c were compared either between themselves or against Arabidopsis thaliana genome which was taken as the base genome. The highest levels of shared genes were found between A. thaliana and Capsella rubella in both MIR319b- and MIR319c-containing genomic segments, and with the closest species of A. thaliana, A. lyrata, only in MIR319a-containing segment. Synteny analysis across 12 genomes (with 30 sub-genomes) revealed MIR319c to be the most conserved MIRNA loci (present in 27 genomes/sub-genomes) followed by MIR319a (present in 23 genomes/sub-genomes); MIR319b was found to be frequently lost (present in 20 genomes/sub-genomes) and thus is under least selection pressure for retention. Genome fractionation revealed extensive and differential loss of MIRNA homeologous loci and flanking genes from various sub-genomes of Brassica species that is in accordance with their older history of polyploidy when compared to Camelina sativa, a recent neopolyploid, where the effect of genome fractionation was least. Finally, estimation of phylogenetic relationship using precursor sequences of MIR319 reveals MIR319a and MIR319b form sister clades, with MIR319c forming a separate clade. An intra-species synteny analysis between MIR319a-, MIR319b-, and MIR319c-containing genomic segments suggests segmental duplications at the base of Brassicaceae to be responsible for the origin of MIR319a and MIR319b.}, } @article {pmid30242439, year = {2018}, author = {Ashfield-Crook, NR and Woodward, Z and Soust, M and Kurtböke, Dİ}, title = {Assessment of the Detrimental Impact of Polyvalent Streptophages Intended to be Used as Biological Control Agents on Beneficial Soil Streptoflora.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1589-1601}, pmid = {30242439}, issn = {1432-0991}, mesh = {Actinobacteria/metabolism ; Antifungal Agents/metabolism ; Biological Control Agents/*metabolism ; Fusarium/metabolism ; Plant Diseases/*microbiology/*prevention & control ; Plant Roots/microbiology ; Rhizoctonia/metabolism ; Rhizosphere ; Soil ; Soil Microbiology ; Streptomyces/*metabolism ; Triticum/microbiology ; }, abstract = {Streptophages are currently being investigated to control potato common scab, however, since a majority of streptophages are reported to be polyvalent, their potential to infect beneficial soil streptomycetes during the application process may have unintended consequences. To test this hypothesis, two phytopathogenic fungi, namely Fusarium solani and Rhizoctonia solani, were tested for their detrimental effect on the test crop wheat (Triticum aestivum cv. Gutha). F. solani caused a significant root weight reduction (34%) in the wheat plant and therefore was tested further in the pot trials with actinomycetes present. Sixty-seven streptomycete isolates from a Tasmanian potato farm were screened for their antifungal abilities against the two phytopathogenic fungi. Four actinomycetes found to be strongly antifungal were then tested for their disease-protective abilities against F. solani in pot trials again using wheat. Addition of the streptomycetes into the container media protected the plants against F. solani, indicating that streptomycetes have a disease-suppressive effect. A further pot trial was conducted to evaluate whether these beneficial streptomycete species would be affected by streptophage treatment and subsequently result in an increased risk of fungal infections. When streptophages were added to the pots, the shoot and root growth of wheat declined by 23.6% and 8.0%, respectively, in the pots with the pathogenic fungus compared to the control pots. These differences might suggest that removal of antifungal streptomycetes by polyvalent phages from plant rhizosphere when biocontrol of plant pathogenic streptomycetes (e.g. Streptomyces scabiei) is targeted might encourage secondary fungal infections in the farm environment. The presented data provide preliminary evidence that streptophage treatment of pathogenic streptomycetes may lead to an aggravated disease risk by soil-borne fungal pathogens when naturally present antagonists are removed. As a result, extensive farm site trials are required to determine the long-term detrimental impact of polyvalent streptophage treatments on beneficial soil streptoflora.}, } @article {pmid30242295, year = {2018}, author = {Kotil, SE and Vetsigian, K}, title = {Emergence of evolutionarily stable communities through eco-evolutionary tunnelling.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1644-1653}, doi = {10.1038/s41559-018-0655-7}, pmid = {30242295}, issn = {2397-334X}, abstract = {Ecological and evolutionary dynamics of communities are inexorably intertwined. The ecological state determines the fate of newly arising mutants, and mutations that increase in frequency can reshape the ecological dynamics. Evolutionary game theory and its extensions within adaptive dynamics have been the mathematical frameworks for understanding this interplay, leading to notions such as evolutionarily stable states (ESS) in which no mutations are favoured, and evolutionary branching points near which the population diversifies. A central assumption behind these theoretical treatments has been that mutations are rare so that the ecological dynamics has time to equilibrate after every mutation. A fundamental question is whether qualitatively new phenomena can arise when mutations are frequent. Here, we describe an adaptive diversification process that robustly leads to complex ESS, despite the fact that such communities are unreachable through a step-by-step evolutionary process. Rather, the system as a whole tunnels between collective states over a short timescale. The tunnelling rate is a sharply increasing function of the rate at which mutations arise in the population. This makes the emergence of ESS communities virtually impossible in small populations, but generic in large ones. Moreover, communities emerging through this process can spatially spread as single replication units that outcompete other communities. Overall, this work provides a qualitatively new mechanism for adaptive diversification and shows that complex structures can generically evolve even when no step-by-step evolutionary path exists.}, } @article {pmid30242294, year = {2018}, author = {Tarnita, CE}, title = {Fast evolution unlocks forbidden communities.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1525-1526}, doi = {10.1038/s41559-018-0688-y}, pmid = {30242294}, issn = {2397-334X}, } @article {pmid30242137, year = {2018}, author = {Ilyin, DV and Goddard, WA and Oppenheim, JJ and Cheng, T}, title = {First-principles-based reaction kinetics from reactive molecular dynamics simulations: Application to hydrogen peroxide decomposition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1701383115}, pmid = {30242137}, issn = {1091-6490}, abstract = {This paper presents our vision of how to use in silico approaches to extract the reaction mechanisms and kinetic parameters for complex condensed-phase chemical processes that underlie important technologies ranging from combustion to chemical vapor deposition. The goal is to provide an analytic description of the detailed evolution of a complex chemical system from reactants through various intermediates to products, so that one could optimize the efficiency of the reactive processes to produce the desired products and avoid unwanted side products. We could start with quantum mechanics (QM) to ensure an accurate description; however, to obtain useful kinetics we need to average over ∼10-nm spatial scales for ∼1 ns, which is prohibitively impractical with QM. Instead, we use the reactive force field (ReaxFF) trained to fit QM to carry out the reactive molecular dynamics (RMD). We focus here on showing that it is practical to extract from such RMD the reaction mechanisms and kinetics information needed to describe the reactions analytically. This analytic description can then be used to incorporate the correct reaction chemistry from the QM/ReaxFF atomistic description into larger-scale simulations of ∼10 nm to micrometers to millimeters to meters using analytic approaches of computational fluid dynamics and/or continuum chemical dynamics. In the paper we lay out the strategy to extract the mechanisms and rate parameters automatically without the necessity of knowing any details of the chemistry. We consider this to be a proof of concept. We refer to the process as RMD2Kin (reactive molecular dynamics to kinetics) for the general approach and as ReaxMD2Kin (ReaxFF molecular dynamics to kinetics) for QM-ReaxFF-based reaction kinetics.}, } @article {pmid30242136, year = {2018}, author = {Kotchen, MJ and Segerson, K}, title = {On the use of group performance and rights for environmental protection and resource management.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802881115}, pmid = {30242136}, issn = {1091-6490}, abstract = {Environmental and natural resource (ENR) policies that focus on group outcomes are common but have received relatively less attention from economists than policies based on individual behavior. Existing research tends to focus on particular contexts, such as water or air quality, fisheries, or land use. This paper discusses unifying themes of group performance policies, along with their advantages and disadvantages. We discuss a range of specific policy instruments, including group-based taxes, subsidies, and fixed penalties. We show how, in principle, group-based policies can be designed to achieve efficient provision of group-level environmental performance; however, in some cases, group policies can lead to suboptimal outcomes. We discuss the incentives for collaboration that can arise when regulators impose group performance policies, and the role that it can play in promoting efficient outcomes. We argue that the success of group-based policies will depend both on how the policy is designed (i.e., the external rewards and penalties) and on how the group operates. This implies potential complementarities between "top-down" regulatory interventions based on group performance and "bottom-up" within-group incentives for self-governance. Our discussion suggests that group performance policies should play a more prominent role in the suite of policy instruments considered by scholars and policymakers concerned with ENR management.}, } @article {pmid30242135, year = {2018}, author = {Lan, J and Lu, H and Samanta, D and Salman, S and Lu, Y and Semenza, GL}, title = {Hypoxia-inducible factor 1-dependent expression of adenosine receptor 2B promotes breast cancer stem cell enrichment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9640-E9648}, pmid = {30242135}, issn = {1091-6490}, mesh = {Breast Neoplasms/genetics/*metabolism/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1/genetics/*metabolism ; MCF-7 Cells ; Neoplasm Proteins/genetics/*metabolism ; Neoplastic Stem Cells/*metabolism/pathology ; Protein Kinase C-delta/genetics/metabolism ; Receptor, Adenosine A2B/*biosynthesis/genetics ; STAT3 Transcription Factor/genetics/metabolism ; }, abstract = {Breast cancer stem cells (BCSCs), which are characterized by a capacity for unlimited self-renewal and for generation of the bulk cancer cell population, play a critical role in cancer relapse and metastasis. Hypoxia is a common feature of the cancer microenvironment that stimulates the specification and maintenance of BCSCs. In this study, we found that hypoxia increased expression of adenosine receptor 2B (A2BR) in human breast cancer cells through the transcriptional activity of hypoxia-inducible factor 1. The binding of adenosine to A2BR promoted BCSC enrichment by activating protein kinase C-δ, which phosphorylated and activated the transcription factor STAT3, leading to increased expression of interleukin 6 and NANOG, two key mediators of the BCSC phenotype. Genetic or pharmacological inhibition of A2BR expression or activity decreased hypoxia- or adenosine-induced BCSC enrichment in vitro, and dramatically impaired tumor initiation and lung metastasis after implantation of MDA-MB-231 human breast cancer cells into the mammary fat pad of immunodeficient mice. These data provide evidence that targeting A2BR might be an effective strategy to eradicate BCSCs.}, } @article {pmid30242134, year = {2018}, author = {Behesti, H and Fore, TR and Wu, P and Horn, Z and Leppert, M and Hull, C and Hatten, ME}, title = {ASTN2 modulates synaptic strength by trafficking and degradation of surface proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9717-E9726}, pmid = {30242134}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 NS096289/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Movement ; Cells, Cultured ; *DNA Copy Number Variations ; Endocytosis ; Glycoproteins/genetics/*metabolism ; Humans ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/genetics/*metabolism ; Neurodevelopmental Disorders/*genetics/pathology ; Protein Transport ; Proteolysis ; Purkinje Cells/metabolism ; Synapses/*physiology ; }, abstract = {Surface protein dynamics dictate synaptic connectivity and function in neuronal circuits. ASTN2, a gene disrupted by copy number variations (CNVs) in neurodevelopmental disorders, including autism spectrum, was previously shown to regulate the surface expression of ASTN1 in glial-guided neuronal migration. Here, we demonstrate that ASTN2 binds to and regulates the surface expression of multiple synaptic proteins in postmigratory neurons by endocytosis, resulting in modulation of synaptic activity. In cerebellar Purkinje cells (PCs), by immunogold electron microscopy, ASTN2 localizes primarily to endocytic and autophagocytic vesicles in the cell soma and in subsets of dendritic spines. Overexpression of ASTN2 in PCs, but not of ASTN2 lacking the FNIII domain, recurrently disrupted by CNVs in patients, including in a family presented here, increases inhibitory and excitatory postsynaptic activity and reduces levels of ASTN2 binding partners. Our data suggest a fundamental role for ASTN2 in dynamic regulation of surface proteins by endocytic trafficking and protein degradation.}, } @article {pmid30242133, year = {2018}, author = {Yan, J and Porch, MW and Court-Vazquez, B and Bennett, MVL and Zukin, RS}, title = {Activation of autophagy rescues synaptic and cognitive deficits in fragile X mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9707-E9716}, pmid = {30242133}, issn = {1091-6490}, support = {R01 MH092877/MH/NIMH NIH HHS/United States ; R01 NS095029/NS/NINDS NIH HHS/United States ; R01 NS108695/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Autophagy ; CA1 Region, Hippocampal/*metabolism/pathology ; Cytoskeletal Proteins/genetics/metabolism ; Disks Large Homolog 4 Protein/genetics/metabolism ; Fragile X Mental Retardation Protein/genetics/metabolism ; Fragile X Syndrome/genetics/*metabolism/pathology ; Mechanistic Target of Rapamycin Complex 1/genetics/metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/genetics/metabolism ; Regulatory-Associated Protein of mTOR/genetics/metabolism ; Synapses/genetics/*metabolism/pathology ; }, abstract = {Fragile X syndrome (FXS) is the most frequent form of heritable intellectual disability and autism. Fragile X (Fmr1-KO) mice exhibit aberrant dendritic spine structure, synaptic plasticity, and cognition. Autophagy is a catabolic process of programmed degradation and recycling of proteins and cellular components via the lysosomal pathway. However, a role for autophagy in the pathophysiology of FXS is, as yet, unclear. Here we show that autophagic flux, a functional readout of autophagy, and biochemical markers of autophagy are down-regulated in hippocampal neurons of fragile X mice. We further show that enhanced activity of mammalian target of rapamycin complex 1 (mTORC1) and translocation of Raptor, a defining component of mTORC1, to the lysosome are causally related to reduced autophagy. Activation of autophagy by delivery of shRNA to Raptor directly into the CA1 of living mice via the lentivirus expression system largely corrects aberrant spine structure, synaptic plasticity, and cognition in fragile X mice. Postsynaptic density protein (PSD-95) and activity-regulated cytoskeletal-associated protein (Arc/Arg3.1), proteins implicated in spine structure and synaptic plasticity, respectively, are elevated in neurons lacking fragile X mental retardation protein. Activation of autophagy corrects PSD-95 and Arc abundance, identifying a potential mechanism by which impaired autophagy is causally related to the fragile X phenotype and revealing a previously unappreciated role for autophagy in the synaptic and cognitive deficits associated with fragile X syndrome.}, } @article {pmid30242132, year = {2018}, author = {Soriano, M and Cavallo, A and D'Ausilio, A and Becchio, C and Fadiga, L}, title = {Movement kinematics drive chain selection toward intention detection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10452-10457}, pmid = {30242132}, issn = {1091-6490}, support = {312919//European Research Council/International ; }, mesh = {Adult ; Biomechanical Phenomena ; Evoked Potentials, Motor/*physiology ; Female ; Humans ; *Intention ; Male ; *Movement ; *Psychomotor Performance ; Transcranial Magnetic Stimulation ; Young Adult ; }, abstract = {The ability to understand intentions based on another's movements is crucial for human interaction. This ability has been ascribed to the so-called motor chaining mechanism: anytime a motor chain is activated (e.g., grasp-to-drink), the observer attributes to the agent the corresponding intention (i.e., to drink) from the first motor act (i.e., the grasp). However, the mechanisms by which a specific chain is selected in the observer remain poorly understood. In the current study, we investigate the possibility that in the absence of discriminative contextual cues, slight kinematic variations in the observed grasp inform mapping to the most probable chain. Chaining of motor acts predicts that, in a sequential grasping task (e.g., grasp-to-drink), electromyographic (EMG) components that are required for the final act [e.g., the mouth-opening mylohyoid (MH) muscle] show anticipatory activation. To test this prediction, we used MH EMG, transcranial magnetic stimulation (TMS; MH motor-evoked potentials), and predictive models of movement kinematics to measure the level and timing of MH activation during the execution (Experiment 1) and the observation (Experiment 2) of reach-to-grasp actions. We found that MH-related corticobulbar excitability during grasping observation varied as a function of the goal (to drink or to pour) and the kinematics of the observed grasp. These results show that subtle changes in movement kinematics drive the selection of the most probable motor chain, allowing the observer to link an observed act to the agent's intention.}, } @article {pmid30241969, year = {2018}, author = {Saurin, AJ and Delfini, MC and Maurel-Zaffran, C and Graba, Y}, title = {The Generic Facet of Hox Protein Function.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {12}, pages = {941-953}, doi = {10.1016/j.tig.2018.08.006}, pmid = {30241969}, issn = {0168-9525}, abstract = {Hox transcription factors are essential to promote morphological diversification of the animal body. A substantial number of studies have focused on how Hox proteins reach functional specificity, an issue that arises from the fact that these transcription factors control distinct developmental functions despite sharing similar molecular properties. In this review, we highlight that, besides specific functions, for which these transcription factors are renowned, Hox proteins also often have nonspecific functions. We next discuss some emerging principles of these generic functions and how they relate to specific functions and explore our current grasp of the underlying molecular mechanisms.}, } @article {pmid30241778, year = {2018}, author = {Kardos, M and Shafer, ABA}, title = {The Peril of Gene-Targeted Conservation.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {827-839}, doi = {10.1016/j.tree.2018.08.011}, pmid = {30241778}, issn = {1872-8383}, abstract = {The genomics revolution has sparked interest in using our increased understanding of the loci involved in phenotypic variation and adaptation to advance the conservation of biodiversity. Despite much interest and discussion, it remains unclear whether, when, and how such analyses should be used to guide conservation action. Such 'gene-targeted' conservation strategies, while promising, are complicated by several factors including the complex genomic architecture of phenotypic variation and the strong potential for undesirable outcomes such as the loss of genome-wide genetic variation and evolutionary potential. We caution against relying on gene-targeted approaches as a conservation silver bullet and propose rigorous criteria to identify situations where gene-targeted approaches are likely to benefit conservation.}, } @article {pmid30241777, year = {2018}, author = {Halsey, LG}, title = {Keeping Slim When Food Is Abundant: What Energy Mechanisms Could Be at Play?.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {745-753}, doi = {10.1016/j.tree.2018.08.004}, pmid = {30241777}, issn = {1872-8383}, abstract = {The obesity epidemic in humans is juxtaposed by observations of passerine birds exhibiting fine-scale body mass regulation. The ecology literature is replete with research into why these animals regulate body weight, citing tradeoffs between competing pressures such as emaciation and predation. Yet studies on the underlying mechanisms of mass regulation in these animals are scarce. Maintaining or decreasing weight could obviously be achieved by limiting food intake. However, there are numerous reasons why an animal may not control ingestion, at least precisely. This Opinion article investigates the plausibility of possible behavioural and physiological mechanisms to adaptively maintain or decrease body mass in birds and other animals. Candidate behavioural mechanisms include exercising and fidgeting, while physiological mechanisms could include reducing digestive efficiency or mitochondrial efficiency.}, } @article {pmid30241569, year = {2018}, author = {Muganyizi, PS and Maswanya, E and Kilima, S and Makuwani, A}, title = {Migration for obstetric care: the impact of regional Obstetric Care Facility Density disparities in Tanzania.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {676}, pmid = {30241569}, issn = {1756-0500}, mesh = {*Delivery, Obstetric ; Female ; *Health Facilities ; Health Services Accessibility ; Humans ; *Maternal Health Services ; Parturition ; Pregnancy ; Tanzania ; }, abstract = {OBJECTIVE: This is an extended analysis of the previously published data to demonstrate the relationship between high Obstetric Care Facility Density (OCFD) and migration for obstetric services in Tanzania.

RESULTS: Overall, regions with excess institutional deliveries had significantly higher OCFD compared to other regions. A consistent pattern was observed whereby regions with excess Institutional deliveries also exhibited the most outstanding OCFD of all the neighbouring regions. The observed patterns of Institutional deliveries and OCFD affirm the hypothesis of immigration for obstetric care services from low to high OCFD regions. Further research is suggested to prove this hypothesis in the field.}, } @article {pmid30241567, year = {2018}, author = {Michelini, S and Balakrishnan, B and Parolo, S and Matone, A and Mullaney, JA and Young, W and Gasser, O and Wall, C and Priami, C and Lombardo, R and Kussmann, M}, title = {A reverse metabolic approach to weaning: in silico identification of immune-beneficial infant gut bacteria, mining their metabolism for prebiotic feeds and sourcing these feeds in the natural product space.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {171}, pmid = {30241567}, issn = {2049-2618}, abstract = {BACKGROUND: Weaning is a period of marked physiological change. The introduction of solid foods and the changes in milk consumption are accompanied by significant gastrointestinal, immune, developmental, and microbial adaptations. Defining a reduced number of infections as the desired health benefit for infants around weaning, we identified in silico (i.e., by advanced public domain mining) infant gut microbes as potential deliverers of this benefit. We then investigated the requirements of these bacteria for exogenous metabolites as potential prebiotic feeds that were subsequently searched for in the natural product space.

RESULTS: Using public domain literature mining and an in silico reverse metabolic approach, we constructed probiotic-prebiotic-food associations, which can guide targeted feeding of immune health-beneficial microbes by weaning food; analyzed competition and synergy for (prebiotic) nutrients between selected microbes; and translated this information into designing an experimental complementary feed for infants enrolled in a pilot clinical trial (http://www.nourishtoflourish.auckland.ac.nz/).

CONCLUSIONS: In this study, we applied a benefit-oriented microbiome research strategy for enhanced early-life immune health. We extended from "classical" to molecular nutrition aiming to identify nutrients, bacteria, and mechanisms that point towards targeted feeding to improve immune health in infants around weaning. Here, we present the systems biology-based approach we used to inform us on the most promising prebiotic combinations known to support growth of beneficial gut bacteria ("probiotics") in the infant gut, thereby favorably promoting development of the immune system.}, } @article {pmid30241565, year = {2018}, author = {Witjaksono, F and Jutamulia, J and Annisa, NG and Prasetya, SI and Nurwidya, F}, title = {Comparison of low calorie high protein and low calorie standard protein diet on waist circumference of adults with visceral obesity and weight cycling.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {674}, pmid = {30241565}, issn = {1756-0500}, mesh = {Adult ; Body Mass Index ; Caloric Restriction ; Diet ; *Diet, Reducing ; *Dietary Proteins ; Female ; Humans ; Indonesia ; Male ; Middle Aged ; Obesity, Abdominal ; Waist Circumference ; Weight Loss ; Young Adult ; }, abstract = {OBJECTIVES: Many individuals with visceral obesity who previously had succeeded in reducing body weight regain and this loss-gain cycle repeats several times which is called as weight cycling. We aimed to evaluate the effect of a low calorie high protein diet (HP) compared to a low calorie standard protein diet (SP) on waist circumference of visceral obese adults with history of weight cycling.

RESULTS: In this open-randomized clinical trial, participants were asked to follow dietary plan with reduction in daily caloric intake ranging from 500 to 1000 kcal from usual daily amount with minimum daily amount of 1000 kcal for 8 weeks and were divided in two groups: HP group with protein as 22-30% total calorie intake; and SP group with protein as 12-20% total calorie intake. There was a statistically significant difference (P < 0.001) between waist circumference before and after the dietary intervention among both groups. Meanwhile, there was no statistically significant difference in the mean reduction of waist circumference between HP and SP groups (P = 0.073). Taken together, the protein proportion does not significantly affected waist circumference. Trial registration ClinicalTrials.gov NCT03374150, 11 December 2017.}, } @article {pmid30241563, year = {2018}, author = {Alemkere, G and Gilagil, G and Gebrehiwot, T and Tilahun, Z and Mengist, HM}, title = {Physicians' utilization of microbiologic reports and determinants of their preference to order culture in Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {675}, pmid = {30241563}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteriological Techniques ; Cross-Sectional Studies ; Decision Making ; Ethiopia ; Female ; Hospitals ; Humans ; Male ; Physicians ; *Practice Patterns, Physicians' ; }, abstract = {OBJECTIVE: The main aim of the study was to assess physicians' utilization of microbiologic reports and determinants of their preference in ordering microbiologic culture among patients with systemic bacterial infection at Tikur Anbessa Specialized Hospital.

RESULTS: Of the total 369 patients observed, 91 (24.7%) had microbiologic reports (culture and gram stain). About 12% of the patients had culture reports of which majority (77.8%) were available after 72 h of the initial antibiotic start. Antimicrobial susceptibility test was done for 83.3% of the positive cultures. Although 99.5% of the patients were initially placed on empiric therapy, adjustment was done in 114 (30.9%) of the patients. Among these patients with adjusted therapy, changes were unrelated to microbiologic reasons in 103 (90.4%) patients. None of these changes were for the reason of streamlining therapy. Prolonged hospital stay (AOR = 2.9, 95% CI 1.2-6.7), senior physician consultation (AOR = 4.1, 95% CI 1.1-17.7) and suspicion of new site of infection (AOR = 2.6, 95% CI 1.1-6.2) were positive independent predictors for physicians' preference in ordering culture.}, } @article {pmid30241537, year = {2018}, author = {Kremling, A and Geiselmann, J and Ropers, D and de Jong, H}, title = {An ensemble of mathematical models showing diauxic growth behaviour.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {82}, pmid = {30241537}, issn = {1752-0509}, abstract = {BACKGROUND: Carbon catabolite repression (CCR) controls the order in which different carbon sources are metabolised. Although this system is one of the paradigms of regulation in bacteria, the underlying mechanisms remain controversial. CCR involves the coordination of different subsystems of the cell - responsible for the uptake of carbon sources, their breakdown for the production of energy and precursors, and the conversion of the latter to biomass. The complexity of this integrated system, with regulatory mechanisms cutting across metabolism, gene expression, and signalling, has motivated important modelling efforts over the past four decades, especially in the enterobacterium Escherichia coli.

RESULTS: Starting from a simple core model with only four intracellular metabolites, we develop an ensemble of model variants, all showing diauxic growth behaviour during a batch process. The model variants fall into one of the four categories: flux balance models, kinetic models with growth dilution, kinetic models with regulation, and resource allocation models. The model variants differ from one another in only a single aspect, each breaking the symmetry between the two substrate assimilation pathways in a different manner, and can be quantitatively compared using a so-called diauxic growth index. For each of the model variants, we predict the behaviour in two new experimental conditions, namely a glucose pulse for a culture growing in minimal medium with lactose and a batch culture with different initial concentrations of the components of the transport systems. When qualitatively comparing these predictions with experimental data for these two conditions, a number of models can be excluded while other model variants are still not discriminable. The best-performing model variants are based on inducer inclusion and activation of enzymatic genes by a global transcription factor, but the other proposed factors may complement these well-known regulatory mechanisms.

CONCLUSIONS: The model ensemble presented here offers a better understanding of the variety of mechanisms that have been proposed to play a role in CCR. In addition, it provides an educational resource for systems biology, as it gives an introduction to a broad range of modeling approaches in the context of a simple but biologically relevant example.}, } @article {pmid30241501, year = {2018}, author = {de Klerk, B and Emam, M and Thompson-Crispi, KA and Sargolzaei, M and van der Poel, JJ and Mallard, BA}, title = {A genome-wide association study for natural antibodies measured in blood of Canadian Holstein cows.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {694}, pmid = {30241501}, issn = {1471-2164}, mesh = {Animals ; Antibodies/*blood/genetics/immunology ; Canada ; Cattle/blood/*genetics ; Female ; Genome-Wide Association Study/*methods ; Genotype ; Immunoglobulin G/blood/*genetics/immunology ; Immunoglobulin M/blood/*genetics/immunology ; Male ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Natural antibodies (NAb) are an important component of the innate immune system, and fight infections as a part of the first line defence. NAb are poly-reactive and can respond non-specifically to antigens. Therefore, NAb may be a key trait when evaluating an animal's potential natural disease resistance. Variation in NAb is caused by both genetic and environmental factors. In this study genetic parameters of NAb were estimated and a genome-wide association study (GWAS) was performed to gain further understanding on the genes that are responsible for the observed genetic variation of NAb in Canadian Holsteins.

RESULTS: In total, blood samples of 1327 cows from 64 farms were studied. NAb binding to keyhole limpet hemocyanin (KLH) were determined via indirect ELISA. Immunoglobulin (Ig) isotypes, IgG and IgM, were evaluated. From the sample population, 925 cows were genotyped for 45,187 markers and each individual marker was tested to detect genetic variation in NAb levels. The relationships among animals was accounted for with genomic relationship. Results show heritabilities of 0.27 ± 0.064 (IgG) and 0.31 ± 0.065 (IgM). In total, 23 SNPs were found to be associated with IgG, but no SNPs were associated with IgM (FDR p-value < 0.05). The significant SNPs were located on autosomal chromosomes 1, 20 and 21 of the cow genome. Functional annotation analysis of the positional candidate genes revealed two sets of genes with biologically relevant functions related to NAb. In one set, seven genes with crucial roles in the production of antibody in B cells were associated with the trafficking of vesicles inside the cells between organelles. In the second set, two genes among positional candidate genes were associated with isotype class-switching and somatic hypermutation of B cells.

CONCLUSIONS: This study demonstrated the possibility of increasing NAb through selective breeding. In addition, the effects of two candidate pathways are proposed for further investigation of NAb production in Holsteins.}, } @article {pmid30241500, year = {2018}, author = {Cogburn, LA and Trakooljul, N and Chen, C and Huang, H and Wu, CH and Carré, W and Wang, X and White, HB}, title = {Transcriptional profiling of liver during the critical embryo-to-hatchling transition period in the chicken (Gallus gallus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {695}, pmid = {30241500}, issn = {1471-2164}, support = {P20 GM103446/GM/NIGMS NIH HHS/United States ; 00-52100-9614 and 2005-35206-15288//U.S. Department of Agriculture/ ; }, mesh = {Animals ; Breeding ; Chick Embryo/growth & development/metabolism ; Chickens/*growth & development/*metabolism ; Embryonic Development ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; High-Throughput Nucleotide Sequencing ; Liver/embryology/growth & development/*metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Although hatching is perhaps the most abrupt and profound metabolic challenge that a chicken must undergo; there have been no attempts to functionally map the metabolic pathways induced in liver during the embryo-to-hatchling transition. Furthermore, we know very little about the metabolic and regulatory factors that regulate lipid metabolism in late embryos or newly-hatched chicks. In the present study, we examined hepatic transcriptomes of 12 embryos and 12 hatchling chicks during the peri-hatch period-or the metabolic switch from chorioallantoic to pulmonary respiration.

RESULTS: Initial hierarchical clustering revealed two distinct, albeit opposing, patterns of hepatic gene expression. Cluster A genes are largely lipolytic and highly expressed in embryos. While, Cluster B genes are lipogenic/thermogenic and mainly controlled by the lipogenic transcription factor THRSPA. Using pairwise comparisons of embryo and hatchling ages, we found 1272 genes that were differentially expressed between embryos and hatchling chicks, including 24 transcription factors and 284 genes that regulate lipid metabolism. The three most differentially-expressed transcripts found in liver of embryos were MOGAT1, DIO3 and PDK4, whereas THRSPA, FASN and DIO2 were highest in hatchlings. An unusual finding was the "ectopic" and extremely high differentially expression of seven feather keratin transcripts in liver of 16 day embryos, which coincides with engorgement of liver with yolk lipids. Gene interaction networks show several transcription factors, transcriptional co-activators/co-inhibitors and their downstream genes that exert a 'ying-yang' action on lipid metabolism during the embryo-to-hatching transition. These upstream regulators include ligand-activated transcription factors, sirtuins and Kruppel-like factors.

CONCLUSIONS: Our genome-wide transcriptional analysis has greatly expanded the hepatic repertoire of regulatory and metabolic genes involved in the embryo-to-hatchling transition. New knowledge was gained on interactive transcriptional networks and metabolic pathways that enable the abrupt switch from ectothermy (embryo) to endothermy (hatchling) in the chicken. Several transcription factors and their coactivators/co-inhibitors appear to exert opposing actions on lipid metabolism, leading to the predominance of lipolysis in embryos and lipogenesis in hatchlings. Our analysis of hepatic transcriptomes has enabled discovery of opposing, interconnected and interdependent transcriptional regulators that provide precise ying-yang or homeorhetic regulation of lipid metabolism during the critical embryo-to-hatchling transition.}, } @article {pmid30241497, year = {2018}, author = {Huang, BH and Lin, YC and Huang, CW and Lu, HP and Luo, MX and Liao, PC}, title = {Differential genetic responses to the stress revealed the mutation-order adaptive divergence between two sympatric ginger species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {692}, pmid = {30241497}, issn = {1471-2164}, support = {(MOST 105-2628-B-003 -002 -MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {*Adaptation, Physiological ; *Genetic Speciation ; Genetics, Population ; Ginger/classification/*genetics ; High-Throughput Nucleotide Sequencing ; *Mutation ; Plant Proteins/*genetics ; *Polymorphism, Single Nucleotide ; RNA, Plant ; *Stress, Physiological ; Sympatry ; }, abstract = {BACKGROUND: Divergent genetic responses to the same environmental pressures may lead sympatric ecological speciation possible. Such speciation process possibly explains rapid sympatric speciation of island species. Two island endemic ginger species Zingiber kawagoii and Z. shuanglongensis was suggested to be independently originated from inland ancestors, but their island endemism and similar morphologies and habitats lead another hypothesis of in situ ecological speciation. For understanding when and how these two species diverged, intraspecific variation was estimated from three chloroplast DNA fragments (cpDNA) and interspecific genome-wide SNPs and expression differences after saline treatment were examined by transcriptomic analyses.

RESULTS: Extremely low intraspecific genetic variation was estimated by cpDNA sequences in both species: nucleotide diversity π = 0.00002 in Z. kawagoii and no nucleotide substitution but only indels found in Z. shuanglongensis. Nonsignificant inter-population genetic differentiation suggests homogenized genetic variation within species. Based on 53,683 SNPs from 13,842 polymorphic transcripts, in which 10,693 SNPs are fixed between species, Z. kawagoii and Z. shuanglongensis were estimated to be diverged since 218~ 238 thousand generations ago (complete divergence since 41.5~ 43.5 thousand generations ago). This time is more recent than the time of Taiwan Island formation. In addition, high proportion of differential expression genes (DEGs) is non-polymorphic or non-positively selected, suggesting key roles of plastic genetic divergence in broaden the selectability in incipient speciation. While some positive selected DEGs were mainly the biotic and abiotic stress-resistance genes, emphasizing the importance of adaptive divergence of stress-related genes in sympatric ecological speciation. Furthermore, the higher proportional expression of functional classes in Z. kawagoii than in Z. shuanglongensis explains the more widespread distribution of Z. kawagoii in Taiwan.

CONCLUSIONS: Our results contradict the previous hypothesis of independent origination of these two island endemic ginger species from SE China and SW China. Adaptive divergent responses to the stress explain how these gingers maintain genetic differentiation in sympatry. However, the recent speciation and rapid expansion make extremely low intraspecific genetic variation in these two species. This study arise a more probable speciation hypothesis of sympatric speciation within an island via the mutation-order mechanism underlying the same environmental pressure.}, } @article {pmid30241496, year = {2018}, author = {Song, Y and Milon, B and Ott, S and Zhao, X and Sadzewicz, L and Shetty, A and Boger, ET and Tallon, LJ and Morell, RJ and Mahurkar, A and Hertzano, R}, title = {A comparative analysis of library prep approaches for sequencing low input translatome samples.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {696}, pmid = {30241496}, issn = {1471-2164}, support = {R01 DC003544/DC/NIDCD NIH HHS/United States ; R01DC03544//National Institute on Deafness and Other Communication Disorders/ ; R01 DC013817/DC/NIDCD NIH HHS/United States ; MR130240//Congressionally Directed Medical Research Programs/ ; R01DC013817//National Institute on Deafness and Other Communication Disorders/ ; }, mesh = {Animals ; *Gene Library ; High-Throughput Nucleotide Sequencing/*methods ; Immunoprecipitation ; Mice ; *Protein Biosynthesis ; Quality Control ; RNA, Messenger/genetics/isolation & purification/*metabolism ; Ribosomes/genetics/*metabolism ; Sequence Analysis, RNA/*veterinary ; *Transcriptome ; }, abstract = {BACKGROUND: Cell type-specific ribosome-pulldown has become an increasingly popular method for analysis of gene expression. It allows for expression analysis from intact tissues and monitoring of protein synthesis in vivo. However, while its utility has been assessed, technical aspects related to sequencing of these samples, often starting with a smaller amount of RNA, have not been reported. In this study, we evaluated the performance of five library prep protocols for ribosome-associated mRNAs when only 250 pg-4 ng of total RNA are used.

RESULTS: We obtained total and RiboTag-IP RNA, in three biological replicates. We compared 5 methods of library preparation for Illumina Next Generation sequencing: NuGEN Ovation RNA-Seq system V2 Kit, TaKaRa SMARTer Stranded Total RNA-Seq Kit, TaKaRa SMART-Seq v4 Ultra Low Input RNA Kit, Illumina TruSeq RNA Library Prep Kit v2 and NEBNext® Ultra™ Directional RNA Library Prep Kit using slightly modified protocols each with 4 ng of total RNA. An additional set of samples was processed using the TruSeq kit with 70 ng, as a 'gold standard' control and the SMART-Seq v4 with 250 pg of total RNA. TruSeq-processed samples had the best metrics overall, with similar results for the 4 ng and 70 ng samples. The results of the SMART-Seq v4 processed samples were similar to TruSeq (Spearman correlation > 0.8) despite using lower amount of input RNA. All RiboTag-IP samples had an increase in the intronic reads compared with the corresponding whole tissue, suggesting that the IP captures some immature mRNAs. The SMARTer-processed samples had a higher representation of ribosomal and non-coding RNAs leading to lower representation of protein coding mRNA. The enrichment or depletion of IP samples compared to corresponding input RNA was similar across all kits except for SMARTer kit.

CONCLUSION: RiboTag-seq can be performed successfully with as little as 250 pg of total RNA when using the SMART-Seq v4 kit and 4 ng when using the modified protocols of other library preparation kits. The SMART-Seq v4 and TruSeq kits resulted in the highest quality libraries. RiboTag IP RNA contains some immature transcripts.}, } @article {pmid30241467, year = {2018}, author = {Chen, EH and Hou, QL and Dou, W and Wei, DD and Yue, Y and Yang, RL and Yu, SF and De Schutter, K and Smagghe, G and Wang, JJ}, title = {RNA-seq analysis of gene expression changes during pupariation in Bactrocera dorsalis (Hendel) (Diptera: Tephritidae).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {693}, pmid = {30241467}, issn = {1471-2164}, mesh = {Animals ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; High-Throughput Nucleotide Sequencing/methods ; Insect Proteins/genetics ; Larva/genetics ; Metamorphosis, Biological ; Sequence Analysis, RNA ; Tephritidae/*genetics/*growth & development ; }, abstract = {BACKGROUND: The oriental fruit fly, Bactrocera dorsalis (Hendel) has been considered to be one of the most important agricultural pest around the world. As a holometabolous insect, larvae must go through a metamorphosis process with dramatic morphological and structural changes to complete their development. To better understand the molecular mechanisms of these changes, RNA-seq of B. dorsalis from wandering stage (WS), late wandering stage (LWS) and white puparium stage (WPS) were performed.

RESULTS: In total, 11,721 transcripts were obtained, out of which 1914 genes (578 up-regulated and 1336 down-regulated) and 2047 genes (655 up-regulated and 1392 down-regulated) were found to be differentially expressed between WS and LWS, as well as between WS and WPS, respectively. Of these DEGs, 1862 and 1996 genes were successfully annotated in various databases. The analysis of RNA-seq data together with qRT-PCR validation indicated that during this transition, the genes in the oxidative phosphorylation pathway, and genes encoding P450s, serine protease inhibitor, and cuticular proteins were down-regulated, while the serine protease genes were up-regulated. Moreover, we found some 20-hydroxyecdysone (20E) biosynthesis and signaling pathway genes had a higher expression in the WS, while the genes responsible for juvenile hormone (JH) synthesis, degradation, signaling and transporter pathways were down-regulated, suggesting these genes might be involved in the process of larval pupariation in B. dorsalis. For the chitinolytic enzymes, the genes encoding chitinases (chitinase 2, chitinase 5, chitinase 8, and chitinase 10) and chitin deacetylase might play the crucial role in the degradation of insect chitin with their expressions significantly increased during the transition. Here, we also found that chitin synthase 1A might be involved in the chitin synthesis of cuticles during the metamorphosis in B. dorsalis.

CONCLUSIONS: Significant changes at transcriptional level were identified during the larval pupariation of B. dorsalis. Importantly, we also obtained a vast quantity of RNA-seq data and identified metamorphosis associated genes, which would all help us to better understand the molecular mechanism of metamorphosis process in B. dorsalis.}, } @article {pmid30241466, year = {2018}, author = {Dalkiran, A and Rifaioglu, AS and Martin, MJ and Cetin-Atalay, R and Atalay, V and Doğan, T}, title = {ECPred: a tool for the prediction of the enzymatic functions of protein sequences based on the EC nomenclature.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {334}, pmid = {30241466}, issn = {1471-2105}, support = {OYP//Yükseköğretim Kurulu/ ; OYP//Yükseköğretim Kurulu/ ; }, mesh = {Algorithms ; Computational Biology/*methods ; Enzymes/*classification/*metabolism ; Humans ; Sequence Analysis, Protein/*methods ; *Software ; *Terminology as Topic ; }, abstract = {BACKGROUND: The automated prediction of the enzymatic functions of uncharacterized proteins is a crucial topic in bioinformatics. Although several methods and tools have been proposed to classify enzymes, most of these studies are limited to specific functional classes and levels of the Enzyme Commission (EC) number hierarchy. Besides, most of the previous methods incorporated only a single input feature type, which limits the applicability to the wide functional space. Here, we proposed a novel enzymatic function prediction tool, ECPred, based on ensemble of machine learning classifiers.

RESULTS: In ECPred, each EC number constituted an individual class and therefore, had an independent learning model. Enzyme vs. non-enzyme classification is incorporated into ECPred along with a hierarchical prediction approach exploiting the tree structure of the EC nomenclature. ECPred provides predictions for 858 EC numbers in total including 6 main classes, 55 subclass classes, 163 sub-subclass classes and 634 substrate classes. The proposed method is tested and compared with the state-of-the-art enzyme function prediction tools by using independent temporal hold-out and no-Pfam datasets constructed during this study.

CONCLUSIONS: ECPred is presented both as a stand-alone and a web based tool to provide probabilistic enzymatic function predictions (at all five levels of EC) for uncharacterized protein sequences. Also, the datasets of this study will be a valuable resource for future benchmarking studies. ECPred is available for download, together with all of the datasets used in this study, at: https://github.com/cansyl/ECPred . ECPred webserver can be accessed through http://cansyl.metu.edu.tr/ECPred.html .}, } @article {pmid30241465, year = {2018}, author = {Massa, AN and Manrique-Carpintero, NC and Coombs, J and Haynes, KG and Bethke, PC and Brandt, TL and Gupta, SK and Yencho, GC and Novy, RG and Douches, DS}, title = {Linkage analysis and QTL mapping in a tetraploid russet mapping population of potato.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {87}, pmid = {30241465}, issn = {1471-2156}, support = {2009-85606-05673//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: Genome-wide single nucleotide polymorphism (SNP) markers coupled with allele dosage information has emerged as a powerful tool for studying complex traits in cultivated autotetraploid potato (Solanum tuberosum L., 2n = 4× = 48). To date, this approach has been effectively applied to the identification of quantitative trait loci (QTLs) underlying highly heritable traits such as disease resistance, but largely unexplored for traits with complex patterns of inheritance.

RESULTS: In this study, an F1 tetraploid russet mapping population (162 individuals) was evaluated for multiple quantitative traits over two years and two locations to identify QTLs associated with tuber sugar concentration, processing quality, vine maturity, and other high-value agronomic traits. We report the linkage maps for the 12 potato chromosomes and the QTL location with corresponding genetic models and candidate SNPs explaining the highest phenotypic variation for tuber quality and maturity related traits. Significant QTLs for tuber glucose concentration and tuber fry color were detected on chromosomes 4, 5, 6, 10, and 11. Collectively, these QTLs explained between 24 and 46% of the total phenotypic variation for tuber glucose and fry color, respectively. The QTL on chromosome 10 was associated with apoplastic invertases, with 'Premier Russet' contributing the favorable allele for fry processing quality. On chromosome 5, minor-effect QTLs for tuber glucose concentration and fry color co-localized with various major-effect QTLs, including vine maturity, growth habit, tuber shape, early blight (Altenaria tenuis), and Verticillium wilt (Verticillium spp.).

CONCLUSIONS: Linkage analysis and QTL mapping in a russet mapping population (A05141) using SNP dosage information successfully identified favorable alleles and candidate SNPs for resistance to the accumulation of tuber reducing sugars. These novel markers have a high potential for the improvement of tuber processing quality. Moreover, the discovery of different genetic models for traits with overlapping QTLs at the maturity locus clearly suggests an independent genetic control.}, } @article {pmid30241464, year = {2018}, author = {Magdevska, L and Mraz, M and Zimic, N and Moškon, M}, title = {Initial state perturbations as a validation method for data-driven fuzzy models of cellular networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {333}, pmid = {30241464}, issn = {1471-2105}, mesh = {Computational Biology/*methods ; *Computer Simulation ; *Fuzzy Logic ; *Gene Regulatory Networks ; Humans ; Systems Biology ; }, abstract = {BACKGROUND: Data-driven methods that automatically learn relations between attributes from given data are a popular tool for building mathematical models in computational biology. Since measurements are prone to errors, approaches dealing with uncertain data are especially suitable for this task. Fuzzy models are one such approach, but they contain a large amount of parameters and are thus susceptible to over-fitting. Validation methods that help detect over-fitting are therefore needed to eliminate inaccurate models.

RESULTS: We propose a method to enlarge the validation datasets on which a fuzzy dynamic model of a cellular network can be tested. We apply our method to two data-driven dynamic models of the MAPK signalling pathway and two models of the mammalian circadian clock. We show that random initial state perturbations can drastically increase the mean error of predictions of an inaccurate computational model, while keeping errors of predictions of accurate models small.

CONCLUSIONS: With the improvement of validation methods, fuzzy models are becoming more accurate and are thus likely to gain new applications. This field of research is promising not only because fuzzy models can cope with uncertainty, but also because their run time is short compared to conventional modelling methods that are nowadays used in systems biology.}, } @article {pmid30241463, year = {2018}, author = {Wang, JH and Chen, YH}, title = {Overlapping group screening for detection of gene-gene interactions: application to gene expression profiles with survival trait.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {335}, pmid = {30241463}, issn = {1471-2105}, support = {MOST 104-2118-M-001-006-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Algorithms ; Carcinoma, Non-Small-Cell Lung/genetics/*mortality ; Computer Simulation ; Databases, Factual ; *Epistasis, Genetic ; Gene Expression Profiling ; *Genetic Loci ; Humans ; Lung Neoplasms/genetics/*mortality ; Lymphoma, Large B-Cell, Diffuse/genetics/*mortality ; Predictive Value of Tests ; Survival Rate ; *Transcriptome ; }, abstract = {BACKGROUND: The development of a disease is a complex process that may result from joint effects of multiple genes. In this article, we propose the overlapping group screening (OGS) approach to determining active genes and gene-gene interactions incorporating prior pathway information. The OGS method is developed to overcome the challenges in genome-wide data analysis that the number of the genes and gene-gene interactions is far greater than the sample size, and the pathways generally overlap with one another. The OGS method is further proposed for patients' survival prediction based on gene expression data.

RESULTS: Simulation studies demonstrate that the performance of the OGS approach in identifying the true main and interaction effects is good and the survival prediction accuracy of OGS with the Lasso penalty is better than the ordinary Lasso method. In real data analysis, we identify several significant genes and/or epistasis interactions that are associated with clinical survival outcomes of diffuse large B-cell lymphoma (DLBCL) and non-small-cell lung cancer (NSCLC) by utilizing prior pathway information from the KEGG pathway and the GO biological process databases, respectively.

CONCLUSIONS: The OGS approach is useful for selecting important genes and epistasis interactions in the ultra-high dimensional feature space. The prediction ability of OGS with the Lasso penalty is better than existing methods. The OGS approach is generally applicable to various types of outcome data (quantitative, qualitative, censored event time data) and regression models (e.g. linear, logistic, and Cox's regression models).}, } @article {pmid30241462, year = {2018}, author = {Cardoso, DC and Heinze, J and Moura, MN and Cristiano, MP}, title = {Chromosomal variation among populations of a fungus-farming ant: implications for karyotype evolution and potential restriction to gene flow.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {146}, pmid = {30241462}, issn = {1471-2148}, support = {PPM0126-15//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/International ; }, mesh = {Animals ; Ants/*genetics/*microbiology ; Centromere/metabolism ; Chromosome Banding ; Chromosomes/*genetics ; *Evolution, Molecular ; Fungi/*physiology ; *Gene Flow ; Genome Size ; *Genome, Insect ; *Karyotype ; Mitosis ; Phylogeny ; }, abstract = {BACKGROUND: Intraspecific variation in chromosome structure may cause genetic incompatibilities and thus provides the first step in the formation of species. In ants, chromosome number varies tremendously from 2n = 2 to 2n = 120, and several studies have revealed considerable variation in karyotype within species. However, most previous studies were limited to the description of chromosome number and morphology, and more detailed karyomorphometric analyses may reveal additional, substantial variation. Here, we studied karyotype length, genome size, and phylogeography of five populations of the fungus-farming ant Trachymyrmex holmgreni in order to detect potential barriers to gene flow.

RESULTS: Chromosome number and morphology did not vary among the five populations, but karyotype length and genome size were significantly higher in the southernmost populations than in the northern populations of this ant. Individuals or colonies with different karyotype lengths were not observed. Karyotype length variation appears to result from variation in centromere length.

CONCLUSION: T. holmgreni shows considerable variation in karyotype length and might provide a second example of centromere drive in ants, similar to what has previously been observed in Solenopsis fire ants. Whether this variation leads to genetic incompatibilities between the different populations remains to be studied.}, } @article {pmid30241460, year = {2018}, author = {Maiolo, M and Zhang, X and Gil, M and Anisimova, M}, title = {Progressive multiple sequence alignment with indel evolution.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {331}, pmid = {30241460}, issn = {1471-2105}, support = {31003A_157064//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 31003A_176316//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {*Algorithms ; *Evolution, Molecular ; Humans ; *INDEL Mutation ; *Phylogeny ; Probability ; Sequence Alignment ; }, abstract = {BACKGROUND: Sequence alignment is crucial in genomics studies. However, optimal multiple sequence alignment (MSA) is NP-hard. Thus, modern MSA methods employ progressive heuristics, breaking the problem into a series of pairwise alignments guided by a phylogeny. Changes between homologous characters are typically modelled by a Markov substitution model. In contrast, the dynamics of indels are not modelled explicitly, because the computation of the marginal likelihood under such models has exponential time complexity in the number of taxa. But the failure to model indel evolution may lead to artificially short alignments due to biased indel placement, inconsistent with phylogenetic relationship.

RESULTS: Recently, the classical indel model TKF91 was modified to describe indel evolution on a phylogeny via a Poisson process, termed PIP. PIP allows to compute the joint marginal probability of an MSA and a tree in linear time. We present a new dynamic programming algorithm to align two MSAs -represented by the underlying homology paths- by full maximum likelihood under PIP in polynomial time, and apply it progressively along a guide tree. We have corroborated the correctness of our method by simulation, and compared it with competitive methods on an illustrative real dataset.

CONCLUSIONS: Our MSA method is the first polynomial time progressive aligner with a rigorous mathematical formulation of indel evolution. The new method infers phylogenetically meaningful gap patterns alternative to the popular PRANK, while producing alignments of similar length. Moreover, the inferred gap patterns agree with what was predicted qualitatively by previous studies. The algorithm is implemented in a standalone C++ program: https://github.com/acg-team/ProPIP . Supplementary data are available at BMC Bioinformatics online.}, } @article {pmid30241459, year = {2018}, author = {Liu, X and Yang, Z and Sang, S and Zhou, Z and Wang, L and Zhang, Y and Lin, H and Wang, J and Xu, B}, title = {Identifying protein complexes based on node embeddings obtained from protein-protein interaction networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {332}, pmid = {30241459}, issn = {1471-2105}, support = {61572098//National Natural Science Foundation of China (CN)/ ; 2016YFC0901902//National Key Research and Development Program of China/ ; 61272373//National Natural Science Foundation of China/ ; NCET-13-0084//Trans-Century Training Program Foundation for the Talents by the Ministry of Education of China/ ; 61572098//National Natural Science Foundation of China/ ; 61572102//National Natural Science Foundation of China/ ; }, mesh = {*Algorithms ; Computational Biology/*methods ; Humans ; Protein Interaction Mapping/*methods ; *Protein Interaction Maps ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {BACKGROUND: Protein complexes are one of the keys to deciphering the behavior of a cell system. During the past decade, most computational approaches used to identify protein complexes have been based on discovering densely connected subgraphs in protein-protein interaction (PPI) networks. However, many true complexes are not dense subgraphs and these approaches show limited performances for detecting protein complexes from PPI networks.

RESULTS: To solve these problems, in this paper we propose a supervised learning method based on network node embeddings which utilizes the informative properties of known complexes to guide the search process for new protein complexes. First, node embeddings are obtained from human protein interaction network. Then the protein interactions are weighted through the similarities between node embeddings. After that, the supervised learning method is used to detect protein complexes. Then the random forest model is used to filter the candidate complexes in order to obtain the final predicted complexes. Experimental results on real human and yeast protein interaction networks show that our method effectively improves the performance for protein complex detection.

CONCLUSIONS: We provided a new method for identifying protein complexes from human and yeast protein interaction networks, which has great potential to benefit the field of protein complex detection.}, } @article {pmid30240912, year = {2019}, author = {Xie, C and Xie, DF and Zhong, Y and Guo, XL and Liu, Q and Zhou, SD and He, XJ}, title = {The effect of Hengduan Mountains Region (HMR) uplift to environmental changes in the HMR and its eastern adjacent area: Tracing the evolutionary history of Allium section Sikkimensia (Amaryllidaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {380-396}, doi = {10.1016/j.ympev.2018.09.011}, pmid = {30240912}, issn = {1095-9513}, abstract = {Exploring the effects of orographic events and climatic shifts on geographic distribution of organism in the Hengduan Mountains Region (HMR) and its eastern adjacent area is crucial to the understanding of the environmental changes to organismal evolution. To gain further insight into these processes, we reconstruct evolutionary history of ten species in Allium section Sikkimensia, distributed across regions abovementioned. Using chloroplast and nuclear sequence variation of 79 populations of these ten Allium species with known morphological preferences, we elucidate the phylogenetic relationship, divergence time, ancestral area and genetic structures. Climatic variables analysis, Isolation by distance (IBD) and environment (IBE) and Species distribution modeling (SDM) were analyzed along different genetic clades. These analyses indicated that the initial split of Sikkimensia was triggered by climate changes following Qinghai-Tibet Plateau sensu lato (QTPsl) uplift during the late Miocene. Subsequently, divergences within lineage (lineage A)/among lineages (lineage C and D) in Sikkimensia may be induced by the intense uplift of the HMR around 3-4 Ma and abrupt intensifying of the Asian monsoon regimes. Furthermore, Sikkimensia populations exhibited lopsided demographic history in the Last Glacial Maximum (LGM), as was indicated by the expansion of their range in the QDM and contraction in the HMR. Our findings appear to suggest that the HMR uplift could have strengthened the orographic difference between the HMR and its eastern adjacent area and led to a colder climate in the HMR, while geological topography also played an important role for taxa to respond the climate change that had taken place in the HMR and its eastern adjacent area during the Pleistocene.}, } @article {pmid30240049, year = {2018}, author = {Wackett, LP}, title = {Global microbial metagenomics: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3127-3128}, doi = {10.1111/1462-2920.14402}, pmid = {30240049}, issn = {1462-2920}, } @article {pmid30240036, year = {2018}, author = {Eyer, PA and Hefetz, A}, title = {Cytonuclear incongruences hamper species delimitation in the socially polymorphic desert ants of the Cataglyphis albicans group in Israel.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1828-1842}, doi = {10.1111/jeb.13378}, pmid = {30240036}, issn = {1420-9101}, support = {844/13//Isreal Science Foundation/ ; }, abstract = {Assessing whether behavioural, ecological or geographical factors trigger population divergence provides key insights into the biological processes driving speciation. Recent speciation in restricted geographic area without obvious ecological barriers prompts the question of the behavioural mechanisms underlying species divergence. In this context, we investigated phylogenetic relationships in the Cataglyphis albicans desert ant complex in Israel. We first determined accurate species delimitation using two mitochondrial and six nuclear genes, as well as 11 microsatellite markers to investigate cryptic species in this group, assessing reduction in gene flow between populations. We then investigated whether different species in this group exhibit distinct reproductive strategies, inferring social structure and queen-mating frequency in each species uncovered. Our findings highlight the presence of at least six distinct Cataglyphis albicans species in the restricted range of Israel; four of them co-occur in a 50 × 50 km area in North Negev, while two are endemic from there. However, our results reveal incongruences between nuclear and mitochondrial clustering, which complicate species identification and preclude the exclusive use of mtDNA to confidently delimit species in this group. Finally, we show that the different species of the C. albicans group in Israel exhibit quite similar reproductive strategies with most of them having colonies headed by a single queen mated with several males; colonies of one species were, however, headed by several queens. Overall, this weak variation across species thereby unlikely represents the main evolutionary force behind speciation of these sympatric species. We then discuss the potential evolutionary processes that underlie speciation in this group in the absence of clear geographical or ecological barriers.}, } @article {pmid30239843, year = {2018}, author = {Hess, J and Skrede, I and Chaib De Mares, M and Hainaut, M and Henrissat, B and Pringle, A}, title = {Rapid Divergence of Genome Architectures Following the Origin of an Ectomycorrhizal Symbiosis in the Genus Amanita.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2786-2804}, pmid = {30239843}, issn = {1537-1719}, abstract = {Fungi are evolutionary shape shifters and adapt quickly to new environments. Ectomycorrhizal (EM) symbioses are mutualistic associations between fungi and plants and have evolved repeatedly and independently across the fungal tree of life, suggesting lineages frequently reconfigure genome content to take advantage of open ecological niches. To date analyses of genomic mechanisms facilitating EM symbioses have involved comparisons of distantly related species, but here, we use the genomes of three EM and two asymbiotic (AS) fungi from the genus Amanita as well as an AS outgroup to study genome evolution following a single origin of symbiosis. Our aim was to identify the defining features of EM genomes, but our analyses suggest no clear differentiation of genome size, gene repertoire size, or transposable element content between EM and AS species. Phylogenetic inference of gene gains and losses suggests the transition to symbiosis was dominated by the loss of plant cell wall decomposition genes, a confirmation of previous findings. However, the same dynamic defines the AS species A. inopinata, suggesting loss is not strictly associated with origin of symbiosis. Gene expansions in the common ancestor of EM Amanita were modest, but lineage specific and large gene family expansions are found in two of the three EM extant species. Even closely related EM genomes appear to share few common features. The genetic toolkit required for symbiosis appears already encoded in the genomes of saprotrophic species, and this dynamic may explain the pervasive, recurrent evolution of ectomycorrhizal associations.}, } @article {pmid30239731, year = {2018}, author = {Stott, M and Lueders, T}, title = {Editorial: Deep life, kia ora!.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy176}, pmid = {30239731}, issn = {1574-6941}, } @article {pmid30239730, year = {2018}, author = {Shapiro, K and Silver, M and Byrne, BA and Berardi, T and Aguilar, B and Melli, A and Smith, WA}, title = {Fecal indicator bacteria and zoonotic pathogens in marine snow and California mussels (Mytilus californianus).}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy172}, pmid = {30239730}, issn = {1574-6941}, abstract = {Pollution of nearshore waters with disease-causing microorganisms impacts ecosystems health through illness and deaths in people and wildlife, as well as negative socioeconomic consequences of impaired marine resources. Insight on pathogen ecology in coastal habitats is crucial for accurately mitigating inputs and impacts of microbial pollution. Three objectives were addressed to (i) compare fecal pollution in proximity to (a) freshwater runoff, and (b) endemic marine wildlife; (ii) evaluate presence and magnitude of fecal microorganisms in marine snow and mussels and (iii) determine if pathogens in mussels and FIB levels in seawater or mussels are correlated. Sampling during the wet season, proximity to freshwater, and FIB levels in mussel homogenates (but not seawater) were associated with pathogen presence in mussels. Pathogens and FIB were enriched in aggregate-rich fractions, further supporting an important role of marine snow in pathogen transmission. The lack of association between FIB in surrounding waters and presence of pathogens in mussels calls into question current regulations for insuring safe seafood to consumers in the United States, and alternative monitoring approaches such as direct testing for select pathogens should be further evaluated.}, } @article {pmid30239729, year = {2018}, author = {Varadharajan, S and Sandve, SR and Gillard, GB and Tørresen, OK and Mulugeta, TD and Hvidsten, TR and Lien, S and Asbjørn Vøllestad, L and Jentoft, S and Nederbragt, AJ and Jakobsen, KS}, title = {The Grayling Genome Reveals Selection on Gene Expression Regulation after Whole-Genome Duplication.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2785-2800}, pmid = {30239729}, issn = {1759-6653}, abstract = {Whole-genome duplication (WGD) has been a major evolutionary driver of increased genomic complexity in vertebrates. One such event occurred in the salmonid family ∼80 Ma (Ss4R) giving rise to a plethora of structural and regulatory duplicate-driven divergence, making salmonids an exemplary system to investigate the evolutionary consequences of WGD. Here, we present a draft genome assembly of European grayling (Thymallus thymallus) and use this in a comparative framework to study evolution of gene regulation following WGD. Among the Ss4R duplicates identified in European grayling and Atlantic salmon (Salmo salar), one-third reflect nonneutral tissue expression evolution, with strong purifying selection, maintained over ∼50 Myr. Of these, the majority reflect conserved tissue regulation under strong selective constraints related to brain and neural-related functions, as well as higher-order protein-protein interactions. A small subset of the duplicates have evolved tissue regulatory expression divergence in a common ancestor, which have been subsequently conserved in both lineages, suggestive of adaptive divergence following WGD. These candidates for adaptive tissue expression divergence have elevated rates of protein coding- and promoter-sequence evolution and are enriched for immune- and lipid metabolism ontology terms. Lastly, lineage-specific duplicate divergence points toward underlying differences in adaptive pressures on expression regulation in the nonanadromous grayling versus the anadromous Atlantic salmon. Our findings enhance our understanding of the role of WGD in genome evolution and highlight cases of regulatory divergence of Ss4R duplicates, possibly related to a niche shift in early salmonid evolution.}, } @article {pmid30239727, year = {2018}, author = {Galindo, LJ and Torruella, G and Moreira, D and Timpano, H and Paskerova, G and Smirnov, A and Nassonova, E and López-García, P}, title = {Evolutionary Genomics of Metchnikovella incurvata (Metchnikovellidae): An Early Branching Microsporidium.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2736-2748}, pmid = {30239727}, issn = {1759-6653}, abstract = {Metchnikovellids are highly specialized hyperparasites, which infect and reproduce inside gregarines (Apicomplexa) inhabiting marine invertebrates. Their phylogenetic affiliation was under constant discussion until recently, when analysis of the first near-complete metchnikovellid genome, that of Amphiamblys sp., placed it in a basal position with respect to most Microsporidia. Microsporidia are a highly diversified lineage of extremely reduced parasites related to Rozellida (Rozellosporidia = Rozellomycota = Cryptomycota) within the Holomycota clade of Opisthokonta. By sequencing DNA from a single-isolated infected gregarine cell we obtained an almost complete genome of a second metchnikovellid species, and the first one of a taxonomically described and well-documented species, Metchnikovella incurvata. Our phylogenomic analyses show that, despite being considerably divergent from each other, M. incurvata forms a monophyletic group with Amphiamplys sp., and confirm that metchnikovellids are one of the deep branches of Microsporidia. Comparative genomic analysis demonstrates that, like most Microsporidia, metchnikovellids lack mitochondrial genes involved in energy transduction and are thus incapable of synthesizing their own ATP via mitochondrial oxidative phosphorylation. They also lack the horizontally acquired ATP transporters widespread in most Microsporidia. We hypothesize that a family of mitochondrial carrier proteins evolved to transport ATP from the host into the metchnikovellid cell. We observe the progressive reduction of genes involved in DNA repair pathways along the evolutionary path of Microsporidia, which might explain, at least partly, the extremely high evolutionary rate of the most derived species. Our data also suggest that genome reduction and acquisition of novel genes co-occurred during the adaptation of Microsporidia to their hosts.}, } @article {pmid30239716, year = {2018}, author = {Biscotti, MA and Barucca, M and Carducci, F and Canapa, A}, title = {New Perspectives on the Evolutionary History of Vitellogenin Gene Family in Vertebrates.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2709-2715}, pmid = {30239716}, issn = {1759-6653}, abstract = {Vitellogenin (Vtg) is a glycolipophosphoprotein produced by oviparous and ovoviviparous species and is the precursor protein of the yolk, an essential nutrient reserve for embryonic development and early larval stages. Vtg is encoded by a family of paralog genes whose number varies in the different vertebrate lineages. Its evolution has been the subject of considerable analyses but it remains still unclear. In this work, microsyntenic and phylogenetic analyses were performed in order to increase our knowledge on the evolutionary history of this gene family in vertebrates. Our results support the hypothesis that the vitellogenin gene family is expanded from two genes both present at the beginning of vertebrate radiation through multiple independent duplication events occurred in the diverse lineages.}, } @article {pmid30239713, year = {2018}, author = {Haverkamp, THA and Geslin, C and Lossouarn, J and Podosokorskaya, OA and Kublanov, I and Nesbø, CL}, title = {Thermosipho spp. Immune System Differences Affect Variation in Genome Size and Geographical Distributions.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2853-2866}, pmid = {30239713}, issn = {1759-6653}, abstract = {Thermosipho species inhabit thermal environments such as marine hydrothermal vents, petroleum reservoirs, and terrestrial hot springs. A 16S rRNA phylogeny of available Thermosipho spp. sequences suggested habitat specialists adapted to living in hydrothermal vents only, and habitat generalists inhabiting oil reservoirs, hydrothermal vents, and hotsprings. Comparative genomics of 15 Thermosipho genomes separated them into three distinct species with different habitat distributions: The widely distributed T. africanus and the more specialized, T. melanesiensis and T. affectus. Moreover, the species can be differentiated on the basis of genome size (GS), genome content, and immune system composition. For instance, the T. africanus genomes are largest and contained the most carbohydrate metabolism genes, which could explain why these isolates were obtained from ecologically more divergent habitats. Nonetheless, all the Thermosipho genomes, like other Thermotogae genomes, show evidence of genome streamlining. GS differences between the species could further be correlated to differences in defense capacities against foreign DNA, which influence recombination via HGT. The smallest genomes are found in T. affectus that contain both CRISPR-cas Type I and III systems, but no RM system genes. We suggest that this has caused these genomes to be almost devoid of mobile elements, contrasting the two other species genomes that contain a higher abundance of mobile elements combined with different immune system configurations. Taken together, the comparative genomic analyses of Thermosipho spp. revealed genetic variation allowing habitat differentiation within the genus as well as differentiation with respect to invading mobile DNA.}, } @article {pmid30239709, year = {2018}, author = {Tiley, GP and Barker, MS and Burleigh, JG}, title = {Assessing the Performance of Ks Plots for Detecting Ancient Whole Genome Duplications.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2882-2898}, pmid = {30239709}, issn = {1759-6653}, abstract = {Genomic data have provided evidence of previously unknown ancient whole genome duplications (WGDs) and highlighted the role of WGDs in the evolution of many eukaryotic lineages. Ancient WGDs often are detected by examining distributions of synonymous substitutions per site (Ks) within a genome, or "Ks plots." For example, WGDs can be detected from Ks plots by using univariate mixture models to identify peaks in Ks distributions. We performed gene family simulation experiments to evaluate the effects of different Ks estimation methods and mixture models on our ability to detect ancient WGDs from Ks plots. The simulation experiments, which accounted for variation in substitution rates and gene duplication and loss rates across gene families, tested the effects of WGD age and gene retention rates following WGD on inferring WGDs from Ks plots. Our simulations reveal limitations of Ks plot analyses. Strict interpretations of mixture model analyses often overestimate the number of WGD events, and Ks plot analyses typically fail to detect WGDs when ≤10% of the duplicated genes are retained following the WGD. However, WGDs can accurately be characterized over an intermediate range of Ks. The simulation results are supported by empirical analyses of transcriptomic data, which also suggest that biases in gene retention likely affect our ability to detect ancient WGDs. Although our results indicate mixture model results should be interpreted with great caution, using node-averaged Ks estimates and applying more appropriate mixture models can improve the accuracy of detecting WGDs.}, } @article {pmid30239708, year = {2018}, author = {Chen, S and Saito, N and Encabo, JR and Yamada, K and Choi, IR and Kishima, Y}, title = {Ancient Endogenous Pararetroviruses in Oryza Genomes Provide Insights into the Heterogeneity of Viral Gene Macroevolution.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2686-2696}, pmid = {30239708}, issn = {1759-6653}, abstract = {Endogenous viral sequences in eukaryotic genomes, such as those derived from plant pararetroviruses (PRVs), can serve as genomic fossils to study viral macroevolution. Many aspects of viral evolutionary rates are heterogeneous, including substitution rate differences between genes. However, the evolutionary dynamics of this viral gene rate heterogeneity (GRH) have been rarely examined. Characterizing such GRH may help to elucidate viral adaptive evolution. In this study, based on robust phylogenetic analysis, we determined an ancient endogenous PRV group in Oryza genomes in the range of being 2.41-15.00 Myr old. We subsequently used this ancient endogenous PRV group and three younger groups to estimate the GRH of PRVs. Long-term substitution rates for the most conserved gene and a divergent gene were 2.69 × 10-8 to 8.07 × 10-8 and 4.72 × 10-8 to 1.42 × 10-7 substitutions/site/year, respectively. On the basis of a direct comparison, a long-term GRH of 1.83-fold was identified between these two genes, which is unexpectedly low and lower than the short-term GRH (>3.40-fold) of PRVs calculated using published data. The lower long-term GRH of PRVs was due to the slightly faster rate decay of divergent genes than of conserved genes during evolution. To the best of our knowledge, we quantified for the first time the long-term GRH of viral genes using paleovirological analyses, and proposed that the GRH of PRVs might be heterogeneous on time scales (time-dependent GRH). Our findings provide special insights into viral gene macroevolution and should encourage a more detailed examination of the viral GRH.}, } @article {pmid30239702, year = {2018}, author = {Jeong, H and Wu, X and Smith, B and Yi, SV}, title = {Genomic Landscape of Methylation Islands in Hymenopteran Insects.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2766-2776}, pmid = {30239702}, issn = {1759-6653}, abstract = {Recent genome-wide DNA methylation analyses of insect genomes accentuate an intriguing contrast compared with those in mammals. In mammals, most CpGs are heavily methylated, with the exceptions of clusters of hypomethylated sites referred to as CpG islands. In contrast, DNA methylation in insects is localized to a small number of CpG sites. Here, we refer to clusters of methylated CpGs as "methylation islands (MIs)," and investigate their characteristics in seven hymenopteran insects with high-quality bisulfite sequencing data. Methylation islands were primarily located within gene bodies. They were significantly overrepresented in exon-intron boundaries, indicating their potential roles in splicing. Methylated CpGs within MIs exhibited stronger evolutionary conservation compared with those outside of MIs. Additionally, genes harboring MIs exhibited higher and more stable levels of gene expression compared with those that do not harbor MIs. The effects of MIs on evolutionary conservation and gene expression are independent and stronger than the effect of DNA methylation alone. These results indicate that MIs may be useful to gain additional insights into understanding the role of DNA methylation in gene expression and evolutionary conservation in invertebrate genomes.}, } @article {pmid30239696, year = {2018}, author = {Cohanim, AB and Amsalem, E and Saad, R and Shoemaker, D and Privman, E}, title = {Evolution of Olfactory Functions on the Fire Ant Social Chromosome.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2947-2960}, pmid = {30239696}, issn = {1759-6653}, abstract = {Understanding the molecular evolutionary basis of social behavior is a major challenge in evolutionary biology. Social insects evolved a complex language of chemical signals to coordinate thousands of individuals. In the fire ant Solenopsis invicta, chemical signals are involved in the determination of a polymorphic social organization. Single-queen (monogyne) or multiqueen (polygyne) social structure is determined by the "social chromosome," a nonrecombining region containing ∼504 genes with two distinct haplotypes, SB and Sb. Monogyne queens are always SBB, while polygyne queens are always SBb. Workers discriminate monogyne from polygyne queens based on olfactory cues. Here, we took an evolutionary genomics approach to search for candidate genes in the social chromosome that could be responsible for this discrimination. We compared the SB and Sb haplotypes and analyzed the evolutionary rates since their divergence. Notably, we identified a cluster of 23 odorant receptors in the nonrecombining region of the social chromosome that stands out in terms of nonsynonymous changes in both haplotypes. The cluster includes twelve genes formed by recent Solenopsis-specific duplications. We found evidence for positive selection on several tree branches and significant differences between the SB and Sb haplotypes of these genes. The most dramatic difference is the complete deletion of two of these genes in Sb. These results suggest that the evolution of polygyne social organization involved adaptations in olfactory genes and opens the way for functional studies of the molecular mechanisms underlying social behavior.}, } @article {pmid30239695, year = {2018}, author = {Wang, P and Moore, BM and Panchy, NL and Meng, F and Lehti-Shiu, MD and Shiu, SH}, title = {Factors Influencing Gene Family Size Variation Among Related Species in a Plant Family, Solanaceae.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2596-2613}, pmid = {30239695}, issn = {1759-6653}, abstract = {Gene duplication and loss contribute to gene content differences as well as phenotypic divergence across species. However, the extent to which gene content varies among closely related plant species and the factors responsible for such variation remain unclear. Here, using the Solanaceae family as a model and Pfam domain families as a proxy for gene families, we investigated variation in gene family sizes across species and the likely factors contributing to the variation. We found that genes in highly variable families have high turnover rates and tend to be involved in processes that have diverged between Solanaceae species, whereas genes in low-variability families tend to have housekeeping roles. In addition, genes in high- and low-variability gene families tend to be duplicated by tandem and whole genome duplication, respectively. This finding together with the observation that genes duplicated by different mechanisms experience different selection pressures suggest that duplication mechanism impacts gene family turnover. We explored using pseudogene number as a proxy for gene loss but discovered that a substantial number of pseudogenes are actually products of pseudogene duplication, contrary to the expectation that most plant pseudogenes are remnants of once-functional duplicates. Our findings reveal complex relationships between variation in gene family size, gene functions, duplication mechanism, and evolutionary rate. The patterns of lineage-specific gene family expansion within the Solanaceae provide the foundation for a better understanding of the genetic basis underlying phenotypic diversity in this economically important family.}, } @article {pmid30239669, year = {2018}, author = {Petrovich, M and Chu, B and Wright, D and Griffin, J and Elfeki, M and Murphy, BT and Poretsky, R and Wells, G}, title = {Antibiotic resistance genes show enhanced mobilization through suspended growth and biofilm-based wastewater treatment processes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy174}, pmid = {30239669}, issn = {1574-6941}, } @article {pmid30239661, year = {2018}, author = {Guégan, M and Minard, G and Tran, FH and Tran Van, V and Dubost, A and Valiente Moro, C}, title = {Short-term impacts of anthropogenic stressors on Aedes albopictus mosquito vector microbiota.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy188}, pmid = {30239661}, issn = {1574-6941}, abstract = {Recent studies have highlighted the potential role of microbiota in the biology of the Aedes albopictus mosquito vector. This species is highly anthropogenic and exhibits marked ecological plasticity, with a resulting high potential to colonize a wide range of habitats-including anthropized areas-under various climatic conditions. We put forward the hypothesis that climate and anthropogenic activities, such as the use of antibiotics in agriculture and human medicine, might affect the mosquito-associated bacterial community. We thus studied the additive impact of a temperature decrease and antibiotic ingestion on the temporal dynamics of Ae. albopictus survival and its associated bacterial communities. The results showed no effects of disturbances on mosquito survival. However, short-term temperature impacts on bacterial diversity were observed, while both the community structure and bacterial diversity were affected by early antibiotic ingestion. The genera Elizabethkingia, Chryseobacterium and Wolbachia, as well as an unclassified member of the Bacteroidales order were particularly affected. Antibiotics negatively impacted Elizabethkingia abundance, while Chryseobacterium was completely eliminated following both disturbances, to the benefit of Wolbachia and the unclassified Bacteroidales species. These results generated fresh insight into the effects of climate and anthropogenic activities such as the use of antibiotics on mosquito microbiota.}, } @article {pmid30239657, year = {2018}, author = {Van Herreweghen, F and De Paepe, K and Roume, H and Kerckhof, FM and Van de Wiele, T}, title = {Mucin degradation niche as a driver of microbiome composition and Akkermansia muciniphila abundance in a dynamic gut model is donor independent.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy186}, pmid = {30239657}, issn = {1574-6941}, abstract = {Akkermansia muciniphila, an abundant mucin degrading intestinal bacterium, has been correlated with human health in various studies. The in vitro SHIME model was used to reach a mechanistic understanding of A. muciniphila's colonization preferences and its response to environmental parameters such as colon pH and mucins. These insight can help to identify the optimal conditions for successful in vivo application. After a period of mucin deprivation, we found that mucin supplementation resulted in significantly different microbial communities, with more Akkermansia, Bacteroides and Ruminococcus. Mucin treatment accounted for 26% of the observed variation in the microbial community at OTU level (P = 0.001), whereas the donor effect was limited (8%) (P = 0.035), indicating mucins to constitute an important ecological niche shaping the microbiota composition. The effect of colonic pH had a less profound impact on the microbiome with both pH and donor origin explaining around 10% of the variability in the dataset. Yet, higher simulated colonic pH had a positive impact on Akkermansia abundance while short chain fatty acid analysis displayed a preference for propionate production with higher colonic pH. Our results show that mucins as nutritional resource are a more important modulator of the gut microbiome than colon pH as environmental factor.}, } @article {pmid30239331, year = {2018}, author = {Omar, AF and Aljmhan, KA and Alsohim, AS and Pérez-López, E}, title = {Potato purple top disease associated with the novel subgroup 16SrII-X phytoplasma.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3678-3682}, doi = {10.1099/ijsem.0.003033}, pmid = {30239331}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; *Phylogeny ; Phytoplasma/*classification/genetics/isolation & purification ; Plant Diseases/*microbiology ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S/genetics ; Saudi Arabia ; Sequence Analysis, DNA ; Solanum tuberosum/*microbiology ; }, abstract = {Potato (Solanum tuberosum) is a very economically important perennial tuberous crop in Saudi Arabia. Potato plants displaying symptoms associated with potato purple top disease, such as aerial tubers and purple and small leaves, were observed in Al-Bukairiyah, Fowlq and Buraydah, Al-Tarafiyah, Qassim governorate, Saudi Arabia. In this study, we examined samples taken from 12 symptomatic potato plants and confirmed the presence of phytoplasma DNA. Analysis of the 16S rRNA-encoding sequences revealed that the symptomatic plants were infected with phytoplasma belonging to the peanut witches'-broom group (16SrII). Sequencing of the 16S rRNA- encoding gene, computer-simulated RFLP analysis and phylogenetic analysis revealed the presence of a novel representative of the 16SrII-X subgroup. The present study identified potato plants as a novel host for novel phytoplasma strains belonging to the pigeon pea witches'-broom group in Saudi Arabia.}, } @article {pmid30239330, year = {2018}, author = {Sarfraz, S and Riaz, K and Oulghazi, S and Cigna, J and Sahi, ST and Khan, SH and Faure, D}, title = {Pectobacterium punjabense sp. nov., isolated from blackleg symptoms of potato plants in Pakistan.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3551-3556}, doi = {10.1099/ijsem.0.003029}, pmid = {30239330}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; Pakistan ; Pectobacterium/*classification/genetics/isolation & purification ; *Phylogeny ; Plant Diseases/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Solanum tuberosum/*microbiology ; }, abstract = {Pectobacterium isolates SS95T, SS54 and SS56 were collected from a potato field in the Chiniot district in the plains of the Punjab province, Pakistan. Sequencing of the gapA barcode revealed that these strains belong to a novel phylogenetic group separated from P.ectobacterium wasabiae and Pectobacterium parmentieri species. Furthermore, multilocus sequence analyses of 13 housekeeping genes (fusA, rpoD, acnA, purA, gyrB, recA, mdh, mtlD, groEL, secY, glyA, gapA and rplB) clearly distinguished the type strain, SS95T, from its closest relatives, i.e. P. parmentieri RNS 08-42-1AT and P. wasabiae CFBP3304T, as well as from all the other known Pectobacteriumspecies. In silico DNA-DNA hybridization (<44.1 %) and average nucleotide identity (<90.75 %) values of strain SS95T compared with other Pectobacterium type strains supported the delineation of a new species. Genomic and phenotypic comparisons permitted the identification of additional traits that distinguished the Pakistani isolates from all other known Pectobacterium type strains. The name Pectobacterium punjabense sp. nov. is proposed for this taxon with the type strain SS95T (=CFBP 8604T=LMG 30622T).}, } @article {pmid30239328, year = {2018}, author = {Park, S and Park, JM and Yoon, JH}, title = {Pseudoruegeria insulae sp. nov., isolated from a tidal flat.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3587-3592}, doi = {10.1099/ijsem.0.003035}, pmid = {30239328}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phosphatidylglycerols/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated BPTF-M20T, was isolated from tidal flat sediment in the Yellow Sea, Republic of Korea. Strain BPTF-M20T grew optimally at 30 °C, at pH 7.0-8.0 and in the presence of 2.0-3.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree of 16S rRNA gene sequences showed that strain BPTF-M20T fell within the clade comprising the type strains of Pseudoruegeria species. Strain BPTF-M20T exhibited 16S rRNA gene sequence similarity values of 97.4-98.3 % to the type strains of Pseudoruegeria haliotis, Pseudoruegeria lutimaris, 'Pseudoruegeria litorisediminis' and Pseudoruegeria sabulilitoris and 96.4-96.9 % to the type strains of the other Pseudoruegeria species. Strain BPTF-M20T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The major polar lipids detected in strain BPTF-M20T were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and one unidentified glycolipid. The DNA G+C content of strain BPTF-M20T was 63.2 mol%. Mean DNA-DNA relatedness values of strain BPTF-M20T with the type strains of P. haliotis, P. lutimaris, P. sabulilitoris and 'P. litorisediminis' were 18-27 %. Differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain BPTF-M20T was separated from recognized Pseudoruegeria species. On the basis of the data presented here, strain BPTF-M20T is considered to represent a novel species of the genus Pseudoruegeria, for which the name Pseudoruegeriainsulae sp. nov. is proposed. The type strain is BPTF-M20T (=KACC 19614T=KCTC 62422T=NBRC 113188T).}, } @article {pmid30239135, year = {2018}, author = {Schulz-Mirbach, T and Ladich, F and Plath, M and Heß, M}, title = {Enigmatic ear stones: what we know about the functional role and evolution of fish otoliths.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12463}, pmid = {30239135}, issn = {1469-185X}, abstract = {Otoliths in bony fishes play an important role in the senses of balance and hearing. Otolith mass and shape are, among others, likely to be decisive factors influencing otolith motion and thus ear functioning. Yet our knowledge of how exactly these factors influence otolith motion is incomplete. In addition, experimental studies directly investigating the function of otoliths in the inner ear are scarce and yield partly conflicting results. Herein, we discuss questions and hypotheses on how otolith mass and shape, and the relationship between the sensory epithelium and overlying otolith, influence otolith motion. We discuss (i) the state-of-the-art knowledge regarding otolith function, (ii) gaps in knowledge that remain to be filled, and (iii) future approaches that may improve our understanding of the role of otoliths in ear functioning. We further link these functional questions to the evolution of solid teleost otoliths instead of numerous tiny otoconia as found in most other vertebrates. Until now, the selective forces and/or constraints driving the evolution of solid calcareous otoliths and their diversity in shape in teleosts are largely unknown. Based on a data set on the structure of otoliths and otoconia in more than 160 species covering the main vertebrate groups, we present a hypothetical framework for teleost otolith evolution. We suggest that the advent of solid otoliths may have initially been a selectively neutral 'by-product' of other key innovations during teleost evolution. The teleost-specific genome duplication event may have paved the way for diversification in otolith shape. Otolith shapes may have evolved along with the considerable diversity of, and improvements in, auditory abilities in teleost fishes. However, phenotypic plasticity may also play an important role in the creation of different otolith types, and different portions of the otolith may show different degrees of phenotypic plasticity. Future studies should thus adopt a phylogenetic perspective and apply comparative and methodologically integrative approaches, including fossil otoliths, when investigating otoconia/otolith evolution and their function in the inner ear.}, } @article {pmid30239126, year = {2018}, author = {Wang, L and Ye, X and Zhao, T}, title = {The physiological roles of autophagy in the mammalian life cycle.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12464}, pmid = {30239126}, issn = {1469-185X}, support = {2018YFA0108402//National Key R&D Program of China/ ; XDA16030302//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; 31720103907//National Natural Science Foundation of China/ ; 31621004//National Natural Science Foundation of China/ ; 31570995//National Natural Science Foundation of China/ ; ZDRW-ZS-2017-5//Key Research Program of the Chinese Academy of Sciences/ ; //National Thousand Young Talents Program/ ; }, abstract = {Autophagy is primarily an efficient intracellular catabolic pathway used for degradation of abnormal cellular protein aggregates and damaged organelles. Although autophagy was initially proposed to be a cellular stress responder, increasing evidence suggests that it carries out normal physiological roles in multiple biological processes. To date, autophagy has been identified in most organs and at many different developmental stages, indicating that it is not only essential for cellular homeostasis and renovation, but is also important for organ development. Herein, we summarize our current understanding of the functions of autophagy (which here refers to macroautophagy) in the mammalian life cycle.}, } @article {pmid30239104, year = {2019}, author = {Prazdnikov, DV and Shkil, FN}, title = {Experimental evidence of the role of heterochrony in evolution of the Mesoamerican cichlids pigment patterns.}, journal = {Evolution & development}, volume = {21}, number = {1}, pages = {3-15}, doi = {10.1111/ede.12272}, pmid = {30239104}, issn = {1525-142X}, abstract = {The Mesoamerican cichlids display a spectacular diversity of pigment patterns, which serve a variety of functions and serve as a strong selective trait for this lineage. The development and variation of coloration in the Mesoamerican cichlids have been detailed by several groups. In particular, Říčan, Musilová, Muška, and Novák () and Říčan, Piálek, Dragová, and Novák () determined homology of pattern and revealed four alternative types of coloration and their ontogeny. In this work, this group posed an "ontogenetic timing hypothesis" proposing heterochronic shifts underlying major transitions in the evolution of the Mesoamerican cichlids. Here, we experimentally test this hypothesis by experimentally altering timing of pigment pattern formation in the convict cichlid Amatitlania nigrofasciata, a member of the Mesoamerican cichlids, via manipulations of thyroid hormone (TH) function. The response of different pigment cell lineages to TH-perturbations revealed that the transition from larval to juvenile coloration in the convict cichlid is under the control of TH-signaling. Importantly, hormonally induced changes in the timing of pigment cell lineages' development resulted in shifts of coloration ontogeny type observed between lineages and led to the appearance of phenotypes mimicking those in phylogenetically close and distant species. Thus, our findings support the hypothesis that simple changes in ontogenetic timing underlies species specific patterns in pigmentation and provide new perspectives for studying the role of endocrine signaling in the evolution of cichlids.}, } @article {pmid30238547, year = {2018}, author = {Takami, Y and Fukuhara, T and Yokoyama, J and Kawata, M}, title = {Impact of sexually antagonistic genital morphologies on female reproduction and wild population demography.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2449-2461}, doi = {10.1111/evo.13603}, pmid = {30238547}, issn = {1558-5646}, support = {24570024//Japan Society for the Promotion of Science JSPS/ ; }, abstract = {Sexual conflict is a strong driver of evolution. The evolutionary outcomes of sexual conflict can, in turn, influence ecological processes within populations, for example, demography. However, evidence for the latter hypothesis is scarce, especially in the wild. Here, we show that sexual conflict is associated with demographic processes determining population size in the ground beetle Carabus insulicola with elaborate male and female genitalia based on individual- and population-level analyses. We found that sexually antagonistic selection can operate on the genitalia: longer male genitalia can be beneficial in sperm competition but decrease female reproductive success with increased egg dumping, whereas longer female genitalia are resistant to this male harassment via decreased egg dumping and increased fertilization rate. As expected from sexually antagonistic coevolution due to sexual conflict, we detected coevolutionary divergence between male and female genital sizes among populations. In parallel with decrease in female reproductive success, more harmful males with longer genitalia and less resistant females with shorter genitalia were related to small effective population sizes. Thus, sexual conflict may promote coevolutionary diversification between sexual traits, and this was associated with a demographic process. Our findings provide an insight into sex-driven eco-evolutionary dynamics in the wild.}, } @article {pmid30238436, year = {2018}, author = {Rundle, HD and Rowe, L}, title = {The contribution of sexual selection to ecological and mutation-order speciation.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2571-2575}, doi = {10.1111/evo.13599}, pmid = {30238436}, issn = {1558-5646}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Abundant evidence supports a role for sexual selection in the evolution of reproductive isolation, and it is thus unsurprising that much attention has been given, both conceptually and empirically, to understanding its role in speciation. In doing so, debate has arisen on how sexual selection fits within the much used ecological versus mutation-order classification of speciation mechanisms, with sexual selection often presented as a distinct third alternative. We argue that models of speciation by sexual selection include a fundamental role of divergent selection between environments or mutation order in initiating the process. Rather than representing a unique mechanism, sexual selection layers a coevolutionary process between males and females on top of the classic mechanisms such that the evolution of each sex can now be driven by divergent selection, mutation order, and selection arising from interactions with the other sex. In addition to blurring the distinction between ecological and mutation-order speciation, this coevolutionary process is likely to speed divergence. Sexual selection is not unique in this way; coevolutionary processes can similarly arise from ecological interactions between populations or species, with similar results. Ultimately, understanding the contribution of sexual selection to speciation will require identifying the processes that drive the divergence of mating biases.}, } @article {pmid30238312, year = {2018}, author = {Frare, R and Ayub, N and Alleva, K and Soto, G}, title = {The Ammonium Channel NOD26 is the Evolutionary Innovation that Drives the Emergence, Consolidation, and Dissemination of Nitrogen-Fixing Symbiosis in Angiosperms.}, journal = {Journal of molecular evolution}, volume = {86}, number = {8}, pages = {554-565}, pmid = {30238312}, issn = {1432-1432}, support = {PICT-2015-0090//Agencia/ ; }, abstract = {Increasing evidence indicates that N-fixing symbiosis has evolved several times in the N-fixing clade of angiosperms and that this evolution is driven by a single evolutionary innovation. However, the genetics of this ancestral predisposition to N-fixing symbiosis remains unclear. A natural candidate for such molecular innovation is the ammonium channel NOD26, the main protein component of the symbiosome membrane, which facilitates the plant uptake of the nitrogen fixed by symbiotic bacteria. Here, in concordance with the emergence of N-fixing symbiosis in angiosperms but not in ancestral plants, phylogenetic analysis showed that NOD26 belongs to an angiosperm-exclusive subgroup of aquaporins. Integrated genomic, phylogenetic, and gene expression analyses supported NOD26 occurrence in the N-fixing clade, the increase in the NOD26 copy number by block and tandem duplications in legumes, and the low-copy number or even the loss of NOD26 in non-legume species of the N-fixing clade, which correlated with the possibility to lose N-fixing symbiosis in legume and non-legume lineages. Metabolic reconstructions showed that retention of NOD26 in N-fixing precursor could represent an adaptive mechanism to bypass energy crisis during anaerobic stress by ammonium detoxification. Finally, we discuss the potential use of NOD26 to transfer N-fixation to non-N-fixing crops as cereals.}, } @article {pmid30238241, year = {2018}, author = {You, J and Hong, S and Yu, J and Duan, L and Liu, B and Mu, B and Zhou, C and Xue, Y}, title = {Coralloluteibacterium thermophilus sp. nov., A Gammaproteobacterium Isolated from an Oil Reservoir.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1584-1588}, pmid = {30238241}, issn = {1432-0991}, support = {2017E-1507//China National Petroleum Corporation/ ; 2017-HB-B19//Huabei Oilfield Company/ ; }, mesh = {Bacterial Typing Techniques/methods ; Base Composition/genetics ; China ; DNA, Bacterial/genetics ; Fatty Acids/genetics ; Gammaproteobacteria/genetics/*isolation & purification ; Gram-Negative Aerobic Bacteria/genetics/*isolation & purification ; Oil and Gas Fields/*microbiology ; Phospholipids/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Soil Microbiology ; }, abstract = {A Gram-negative, yellow-pigmented, aerobic bacterium, designated strain B51-30T, was isolated from oil-well production liquid in Baolige oilfield, China. The strain was able to grow at pH 6-10 (optimum at pH 7.5), in 0-6% (w/v) NaCl (optimum at 1%, w/v) at 15-55 °C (optimum at 45 °C). Cells of the isolate were non-motile and non-spore-forming rods. The major cellular fatty acids were iso-C15:0, iso-C11:0, iso-C11:0 3OH, iso-C17:1 ω9c, and iso-C17:0. Ubiquinone 8 was the predominant respiratory quinone. The major polar lipids consisted of phosphatidylethanolamine and diphosphatidylglycerol. The genomic DNA G+C content of the isolate was 70.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain B51-30T was most closely related to Coralloluteibacterium stylophorae KCTC 52167T (98.7% similarity). The two strains showed DNA-DNA relatedness values of 58.5%. Genotypic and phenotypic features indicate that strain B51-30T represents a novel species of the genus Coralloluteibacterium, for which the name Coralloluteibacterium thermophilus sp. nov. is proposed. The type strain is B51-30T (= CGMCC 1.13574T = KCTC 62780T).}, } @article {pmid30237543, year = {2018}, author = {Beardmore, RE and Cook, E and Nilsson, S and Smith, AR and Tillmann, A and Esquivel, BD and Haynes, K and Gow, NAR and Brown, AJP and White, TC and Gudelj, I}, title = {Author Correction: Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1824}, doi = {10.1038/s41559-018-0678-0}, pmid = {30237543}, issn = {2397-334X}, abstract = {In the version of this Article originally published, the following sentence was missing from the Acknowledgements: "R.E.B. is an EPSRC Healthcare Technologies Impact Fellow EP/N033671/1; I.G. is funded by ERC Consolidator grant 647292 MathModExp; A.J.P.B., N.A.R.G. and A.T. were funded by BBSRC grant BB/F00513X/1; K.H., I.G., S.N. and E.C. were funded by BBSRC grant BB/F005210/2." This text has now been added.}, } @article {pmid30237491, year = {2018}, author = {Du Toit, A}, title = {Exporting electrons.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {657}, doi = {10.1038/s41579-018-0088-y}, pmid = {30237491}, issn = {1740-1534}, } @article {pmid30237480, year = {2018}, author = {Leo, N and Carolus, V and White, JS and Kenzelmann, M and Hudl, M and Tolédano, P and Honda, T and Kimura, T and Ivanov, SA and Weil, M and Lottermoser, T and Meier, D and Fiebig, M}, title = {Publisher Correction: Magnetoelectric inversion of domain patterns.}, journal = {Nature}, volume = {563}, number = {7732}, pages = {E29}, doi = {10.1038/s41586-018-0560-x}, pmid = {30237480}, issn = {1476-4687}, abstract = {Four incorrect figure citations in this Letter have been corrected online.}, } @article {pmid30237447, year = {2018}, author = {Sheth, RU and Wang, HH}, title = {DNA-based memory devices for recording cellular events.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {718-732}, doi = {10.1038/s41576-018-0052-8}, pmid = {30237447}, issn = {1471-0064}, support = {R01 AI132403/AI/NIAID NIH HHS/United States ; }, abstract = {Measuring biological data across time and space is critical for understanding complex biological processes and for various biosurveillance applications. However, such data are often inaccessible or difficult to directly obtain. Less invasive, more robust and higher-throughput biological recording tools are needed to profile cells and their environments. DNA-based cellular recording is an emerging and powerful framework for tracking intracellular and extracellular biological events over time across living cells and populations. Here, we review and assess DNA recorders that utilize CRISPR nucleases, integrases and base-editing strategies, as well as recombinase and polymerase-based methods. Quantitative characterization, modelling and evaluation of these DNA-recording modalities can guide their design and implementation for specific application areas.}, } @article {pmid30237445, year = {2018}, author = {Halldorsson, BV and Hardarson, MT and Kehr, B and Styrkarsdottir, U and Gylfason, A and Thorleifsson, G and Zink, F and Jonasdottir, A and Jonasdottir, A and Sulem, P and Masson, G and Thorsteinsdottir, U and Helgason, A and Kong, A and Gudbjartsson, DF and Stefansson, K}, title = {Author Correction: The rate of meiotic gene conversion varies by sex and age.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1616}, doi = {10.1038/s41588-018-0228-3}, pmid = {30237445}, issn = {1546-1718}, abstract = {In the version of this article published, statements about the impact of insertions and deletions on gene conversions were incorrect. We reported a bias toward deletions, whereas in fact the bias was toward insertions. We are deeply indebted to Laurent Duret and Brice Letcher for noticing this mistake in our manuscript. The following statements are incorrect in the published manuscript.}, } @article {pmid30237358, year = {2018}, author = {Wanchisen, BA}, title = {Afraid to fail? Reach out.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1278}, doi = {10.1126/science.361.6408.1278}, pmid = {30237358}, issn = {1095-9203}, mesh = {*Career Choice ; Interpersonal Relations ; Psychology/*education ; }, } @article {pmid30237357, year = {2018}, author = {Gao, XJ and Chong, LS and Kim, MS and Elowitz, MB}, title = {Programmable protein circuits in living cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1252-1258}, doi = {10.1126/science.aat5062}, pmid = {30237357}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bioengineering/*methods ; Caspases/metabolism ; Endopeptidases/metabolism ; Enzyme Activation ; Protein Engineering ; Protein Interaction Maps ; Synthetic Biology ; }, abstract = {Synthetic protein-level circuits could enable engineering of powerful new cellular behaviors. Rational protein circuit design would be facilitated by a composable protein-protein regulation system in which individual protein components can regulate one another to create a variety of different circuit architectures. In this study, we show that engineered viral proteases can function as composable protein components, which can together implement a broad variety of circuit-level functions in mammalian cells. In this system, termed CHOMP (circuits of hacked orthogonal modular proteases), input proteases dock with and cleave target proteases to inhibit their function. These components can be connected to generate regulatory cascades, binary logic gates, and dynamic analog signal-processing functions. To demonstrate the utility of this system, we rationally designed a circuit that induces cell death in response to upstream activators of the Ras oncogene. Because CHOMP circuits can perform complex functions yet be encoded as single transcripts and delivered without genomic integration, they offer a scalable platform to facilitate protein circuit engineering for biotechnological applications.}, } @article {pmid30237356, year = {2018}, author = {Jones, KE and Angielczyk, KD and Polly, PD and Head, JJ and Fernandez, V and Lungmus, JK and Tulga, S and Pierce, SE}, title = {Fossils reveal the complex evolutionary history of the mammalian regionalized spine.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1249-1252}, doi = {10.1126/science.aar3126}, pmid = {30237356}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Fossils/*anatomy & histology ; Mammals/*anatomy & histology/genetics/physiology ; Paleontology ; Spine/*anatomy & histology/physiology ; Vertebrates/anatomy & histology/classification/physiology ; }, abstract = {A unique characteristic of mammals is a vertebral column with anatomically distinct regions, but when and how this trait evolved remains unknown. We reconstructed vertebral regions and their morphological disparity in the extinct forerunners of mammals, the nonmammalian synapsids, to elucidate the evolution of mammalian axial differentiation. Mapping patterns of regionalization and disparity (heterogeneity) across amniotes reveals that both traits increased during synapsid evolution. However, the onset of regionalization predates increased heterogeneity. On the basis of inferred homology patterns, we propose a "pectoral-first" hypothesis for region acquisition, whereby evolutionary shifts in forelimb function in nonmammalian therapsids drove increasing vertebral modularity prior to differentiation of the vertebral column for specialized functions in mammals.}, } @article {pmid30237355, year = {2018}, author = {Bobrovskiy, I and Hope, JM and Ivantsov, A and Nettersheim, BJ and Hallmann, C and Brocks, JJ}, title = {Ancient steroids establish the Ediacaran fossil Dickinsonia as one of the earliest animals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1246-1249}, doi = {10.1126/science.aat7228}, pmid = {30237355}, issn = {1095-9203}, mesh = {Animals ; Biological Evolution ; Biomarkers/analysis ; Biota ; Fossils/*anatomy & histology ; Geologic Sediments ; Invertebrates/*anatomy & histology/chemistry/*classification ; Paleontology ; Russia ; Steroids/analysis ; }, abstract = {The enigmatic Ediacara biota (571 million to 541 million years ago) represents the first macroscopic complex organisms in the geological record and may hold the key to our understanding of the origin of animals. Ediacaran macrofossils are as "strange as life on another planet" and have evaded taxonomic classification, with interpretations ranging from marine animals or giant single-celled protists to terrestrial lichens. Here, we show that lipid biomarkers extracted from organically preserved Ediacaran macrofossils unambiguously clarify their phylogeny. Dickinsonia and its relatives solely produced cholesteroids, a hallmark of animals. Our results make these iconic members of the Ediacara biota the oldest confirmed macroscopic animals in the rock record, indicating that the appearance of the Ediacara biota was indeed a prelude to the Cambrian explosion of animal life.}, } @article {pmid30237354, year = {2018}, author = {Yamagishi, H and Sato, H and Hori, A and Sato, Y and Matsuda, R and Kato, K and Aida, T}, title = {Self-assembly of lattices with high structural complexity from a geometrically simple molecule.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1242-1246}, doi = {10.1126/science.aat6394}, pmid = {30237354}, issn = {1095-9203}, abstract = {Here we report an anomalous porous molecular crystal built of C-H···N-bonded double-layered roof-floor components and wall components of a segregatively interdigitated architecture. This complicated porous structure consists of only one type of fully aromatic multijoint molecule carrying three identical dipyridylphenyl wedges. Despite its high symmetry, this molecule accomplishes difficult tasks by using two of its three wedges for roof-floor formation and using its other wedge for wall formation. Although a C-H···N bond is extremely labile, the porous crystal maintains its porosity until thermal breakdown of the C-H···N bonds at 202°C occurs, affording a nonporous polymorph. Though this nonporous crystal survives even at 325°C, it can retrieve the parent porosity under acetonitrile vapor. These findings show how one can translate simplicity into ultrahigh complexity.}, } @article {pmid30237353, year = {2018}, author = {Opremcak, A and Pechenezhskiy, IV and Howington, C and Christensen, BG and Beck, MA and Leonard, E and Suttle, J and Wilen, C and Nesterov, KN and Ribeill, GJ and Thorbeck, T and Schlenker, F and Vavilov, MG and Plourde, BLT and McDermott, R}, title = {Measurement of a superconducting qubit with a microwave photon counter.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1239-1242}, doi = {10.1126/science.aat4625}, pmid = {30237353}, issn = {1095-9203}, abstract = {Fast, high-fidelity measurement is a key ingredient for quantum error correction. Conventional approaches to the measurement of superconducting qubits, involving linear amplification of a microwave probe tone followed by heterodyne detection at room temperature, do not scale well to large system sizes. We introduce an approach to measurement based on a microwave photon counter demonstrating raw single-shot measurement fidelity of 92%. Moreover, the intrinsic damping of the photon counter is used to extract the energy released by the measurement process, allowing repeated high-fidelity quantum nondemolition measurements. Our scheme provides access to the classical outcome of projective quantum measurement at the millikelvin stage and could form the basis for a scalable quantum-to-classical interface.}, } @article {pmid30237352, year = {2018}, author = {Benomar, O and Bazot, M and Nielsen, MB and Gizon, L and Sekii, T and Takata, M and Hotta, H and Hanasoge, S and Sreenivasan, KR and Christensen-Dalsgaard, J}, title = {Asteroseismic detection of latitudinal differential rotation in 13 Sun-like stars.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1231-1234}, doi = {10.1126/science.aao6571}, pmid = {30237352}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The differentially rotating outer layers of stars are thought to play a role in driving their magnetic activity, but the underlying mechanisms that generate and sustain differential rotation are poorly understood. We report the measurement using asteroseismology of latitudinal differential rotation in the convection zones of 40 Sun-like stars. For the most significant detections, the stars' equators rotate approximately twice as fast as their midlatitudes. The latitudinal shear inferred from asteroseismology is much larger than predictions from numerical simulations.}, } @article {pmid30237351, year = {2018}, author = {Bédard, AC and Adamo, A and Aroh, KC and Russell, MG and Bedermann, AA and Torosian, J and Yue, B and Jensen, KF and Jamison, TF}, title = {Reconfigurable system for automated optimization of diverse chemical reactions.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1220-1225}, doi = {10.1126/science.aat0650}, pmid = {30237351}, issn = {1095-9203}, abstract = {Chemical synthesis generally requires labor-intensive, sometimes tedious trial-and-error optimization of reaction conditions. Here, we describe a plug-and-play, continuous-flow chemical synthesis system that mitigates this challenge with an integrated combination of hardware, software, and analytics. The system software controls the user-selected reagents and unit operations (reactors and separators), processes reaction analytics (high-performance liquid chromatography, mass spectrometry, vibrational spectroscopy), and conducts automated optimizations. The capabilities of this system are demonstrated in high-yielding implementations of C-C and C-N cross-coupling, olefination, reductive amination, nucleophilic aromatic substitution (SNAr), photoredox catalysis, and a multistep sequence. The graphical user interface enables users to initiate optimizations, monitor progress remotely, and analyze results. Subsequent users of an optimized procedure need only download an electronic file, comparable to a smartphone application, to implement the protocol on their own apparatus.}, } @article {pmid30237350, year = {2018}, author = {Warren, D}, title = {Science outreach in the Borneo jungle.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1209}, doi = {10.1126/science.aat6367}, pmid = {30237350}, issn = {1095-9203}, } @article {pmid30237349, year = {2018}, author = {Aqorau, T and Bell, J and Kittinger, JN}, title = {Good governance for migratory species.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1208-1209}, doi = {10.1126/science.aav2051}, pmid = {30237349}, issn = {1095-9203}, } @article {pmid30237348, year = {2018}, author = {Sonne, C and Jepson, PD and Desforges, JP and Alstrup, AKO and Olsen, MT and Eulaers, I and Hansen, M and Letcher, RJ and McKinney, MA and Dietz, R}, title = {Pollution threatens toothed whales.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1208}, doi = {10.1126/science.aav2403}, pmid = {30237348}, issn = {1095-9203}, mesh = {Animals ; Environmental Pollution ; *Phylogeny ; *Whales ; }, } @article {pmid30237347, year = {2018}, author = {Middleton, GD}, title = {Bang or whimper?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1204-1205}, doi = {10.1126/science.aau8834}, pmid = {30237347}, issn = {1095-9203}, } @article {pmid30237346, year = {2018}, author = {Hoffman, BU and Lumpkin, EA}, title = {A gut feeling.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1203-1204}, doi = {10.1126/science.aau9973}, pmid = {30237346}, issn = {1095-9203}, mesh = {Brain/*physiology ; Gastrointestinal Tract/*physiology ; *Sensation ; }, } @article {pmid30237345, year = {2018}, author = {Prud'homme, B and Gompel, N}, title = {A bird's inner stripes.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1202-1203}, doi = {10.1126/science.aau5103}, pmid = {30237345}, issn = {1095-9203}, mesh = {Animals ; *Birds ; }, } @article {pmid30237344, year = {2018}, author = {Yang, L}, title = {Fighting chaos with chaos in lasers.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1201}, doi = {10.1126/science.aau6628}, pmid = {30237344}, issn = {1095-9203}, mesh = {*Computer-Aided Design ; *Lasers ; }, } @article {pmid30237343, year = {2018}, author = {Glass, DS and Alon, U}, title = {Programming cells and tissues.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1199-1200}, doi = {10.1126/science.aav2497}, pmid = {30237343}, issn = {1095-9203}, } @article {pmid30237342, year = {2018}, author = {Summons, RE and Erwin, DH}, title = {Chemical clues to the earliest animal fossils.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1198-1199}, doi = {10.1126/science.aau9710}, pmid = {30237342}, issn = {1095-9203}, } @article {pmid30237341, year = {2018}, author = {Azoulay, P and Graff-Zivin, J and Uzzi, B and Wang, D and Williams, H and Evans, JA and Jin, GZ and Lu, SF and Jones, BF and Börner, K and Lakhani, KR and Boudreau, KJ and Guinan, EC}, title = {Toward a more scientific science.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1194-1197}, doi = {10.1126/science.aav2484}, pmid = {30237341}, issn = {1095-9203}, support = {UL1 TR001102/TR/NCATS NIH HHS/United States ; R01 LM012832/LM/NLM NIH HHS/United States ; P01 AG039347/AG/NIA NIH HHS/United States ; U01 CA198934/CA/NCI NIH HHS/United States ; }, } @article {pmid30237340, year = {2018}, author = {Kupferschmidt, K}, title = {A recipe for rigor.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1192-1193}, doi = {10.1126/science.361.6408.1192}, pmid = {30237340}, issn = {1095-9203}, mesh = {Data Collection ; Psychology/*methods ; *Research Design ; }, } @article {pmid30237339, year = {2018}, author = {Stokstad, E}, title = {The truth squad.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1189-1191}, doi = {10.1126/science.361.6408.1189}, pmid = {30237339}, issn = {1095-9203}, mesh = {Algorithms ; Psychology/*methods/trends ; *Research Design ; Scientific Misconduct ; *Statistics as Topic ; }, } @article {pmid30237338, year = {2018}, author = {de Vrieze, J}, title = {The metawars.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1184-1188}, doi = {10.1126/science.361.6408.1184}, pmid = {30237338}, issn = {1095-9203}, mesh = {Aggression ; Mass Media ; *Meta-Analysis as Topic ; Review Literature as Topic ; *Video Games ; *Violence ; }, } @article {pmid30237337, year = {2018}, author = {Couzin-Frankel, J}, title = {Journals under the microscope.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1180-1183}, doi = {10.1126/science.361.6408.1180}, pmid = {30237337}, issn = {1095-9203}, mesh = {Biological Science Disciplines ; Chicago ; *Medicine ; *Peer Review ; *Periodicals as Topic ; *Research ; }, } @article {pmid30237336, year = {2018}, author = {Enserink, M}, title = {Research on research.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1178-1179}, doi = {10.1126/science.361.6408.1178}, pmid = {30237336}, issn = {1095-9203}, mesh = {Metadata ; *Periodicals as Topic ; *Research ; *Science ; }, } @article {pmid30237335, year = {2018}, author = {Servick, K}, title = {Brain scientists dive into deep neural networks.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1177}, doi = {10.1126/science.361.6408.1177}, pmid = {30237335}, issn = {1095-9203}, mesh = {Brain/*physiology ; Humans ; *Nerve Net ; Neural Networks (Computer) ; *Neurosciences/methods ; }, } @article {pmid30237334, year = {2018}, author = {Pennisi, E}, title = {A modular backbone aided the rise of mammals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1176}, doi = {10.1126/science.361.6408.1176}, pmid = {30237334}, issn = {1095-9203}, } @article {pmid30237333, year = {2018}, author = {Wadman, M}, title = {AAAS adopts new policy for ejecting harassers.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1175}, doi = {10.1126/science.361.6408.1175}, pmid = {30237333}, issn = {1095-9203}, mesh = {Female ; Humans ; Male ; Periodicals as Topic/*ethics/legislation & jurisprudence ; Science ; *Sexual Harassment ; *Social Control Policies ; }, } @article {pmid30237332, year = {2018}, author = {Wadman, M}, title = {Drug pair shows promise for treating sleep apnea.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1174-1175}, doi = {10.1126/science.361.6408.1174}, pmid = {30237332}, issn = {1095-9203}, mesh = {Airway Obstruction/drug therapy ; Atomoxetine Hydrochloride/administration & dosage/*adverse effects ; Humans ; Mandelic Acids/administration & dosage/*adverse effects ; Sleep Apnea, Obstructive/*drug therapy/physiopathology ; }, } @article {pmid30237331, year = {2018}, author = {Enserink, M}, title = {Evidence-based medicine group expels internal critic.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1173-1174}, doi = {10.1126/science.361.6408.1173}, pmid = {30237331}, issn = {1095-9203}, mesh = {Drug Industry ; Evidence-Based Medicine/*ethics ; Governing Board/ethics ; *Review Literature as Topic ; }, } @article {pmid30237330, year = {2018}, author = {Schembri, F}, title = {Deadly storms break records, damage facilities.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1172-1173}, doi = {10.1126/science.361.6408.1172}, pmid = {30237330}, issn = {1095-9203}, mesh = {*Climate ; *Cyclonic Storms ; *Disasters ; Far East ; North Carolina ; Statistics as Topic ; United States ; }, } @article {pmid30237329, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1170-1171}, doi = {10.1126/science.361.6408.1170}, pmid = {30237329}, issn = {1095-9203}, } @article {pmid30237328, year = {2018}, author = {Hamburg, M and Hockfield, S and Chu, S}, title = {Address harassment now.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1167}, doi = {10.1126/science.aav4171}, pmid = {30237328}, issn = {1095-9203}, mesh = {Female ; Humans ; Male ; *National Academy of Sciences (U.S.) ; *Sexual Harassment ; United States ; }, } @article {pmid30237327, year = {2018}, author = {Andrews, LB and Nielsen, AAK and Voigt, CA}, title = {Cellular checkpoint control using programmable sequential logic.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aap8987}, pmid = {30237327}, issn = {1095-9203}, mesh = {*Cell Cycle Checkpoints ; Escherichia coli/*cytology/*genetics ; *Gene Regulatory Networks ; Logic ; Synthetic Biology/*methods ; }, abstract = {Biological processes that require orderly progression, such as growth and differentiation, proceed via regulatory checkpoints where the cell waits for signals before continuing to the next state. Implementing such control would allow genetic engineers to divide complex tasks into stages. We present genetic circuits that encode sequential logic to instruct Escherichia coli to proceed through a linear or cyclical sequence of states. These are built with 11 set-reset latches, designed with repressor-based NOR gates, which can connect to each other and sensors. The performance of circuits with up to three latches and four sensors, including a gated D latch, closely match predictions made by using nonlinear dynamics. Checkpoint control is demonstrated by switching cells between multiple circuit states in response to external signals over days.}, } @article {pmid30237326, year = {2018}, author = {Rong, Y and Hu, Y and Mei, A and Tan, H and Saidaminov, MI and Seok, SI and McGehee, MD and Sargent, EH and Han, H}, title = {Challenges for commercializing perovskite solar cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aat8235}, pmid = {30237326}, issn = {1095-9203}, abstract = {Perovskite solar cells (PSCs) have witnessed rapidly rising power conversion efficiencies, together with advances in stability and upscaling. Despite these advances, their limited stability and need to prove upscaling remain crucial hurdles on the path to commercialization. We summarize recent advances toward commercially viable PSCs and discuss challenges that remain. We expound the development of standardized protocols to distinguish intrinsic and extrinsic degradation factors in perovskites. We review accelerated aging tests in both cells and modules and discuss the prediction of lifetimes on the basis of degradation kinetics. Mature photovoltaic solutions, which have demonstrated excellent long-term stability in field applications, offer the perovskite community valuable insights into clearing the hurdles to commercialization.}, } @article {pmid30237325, year = {2018}, author = {Kaelberer, MM and Buchanan, KL and Klein, ME and Barth, BB and Montoya, MM and Shen, X and Bohórquez, DV}, title = {A gut-brain neural circuit for nutrient sensory transduction.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aat5236}, pmid = {30237325}, issn = {1095-9203}, support = {K01 DK103832/DK/NIDDK NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; R03 DK114500/DK/NIDDK NIH HHS/United States ; OT2 OD023849/OD/NIH HHS/United States ; }, mesh = {Animals ; Brain Stem/*physiology ; Electrophysiological Phenomena ; Enteroendocrine Cells/cytology/*metabolism ; Green Fluorescent Proteins/metabolism ; Intestine, Small/*cytology/physiology ; Mice ; Neurons/cytology ; Signal Transduction ; *Synapses ; Vagus Nerve/physiology ; Vesicular Glutamate Transport Protein 1/metabolism ; }, abstract = {The brain is thought to sense gut stimuli only via the passive release of hormones. This is because no connection has been described between the vagus and the putative gut epithelial sensor cell-the enteroendocrine cell. However, these electrically excitable cells contain several features of epithelial transducers. Using a mouse model, we found that enteroendocrine cells synapse with vagal neurons to transduce gut luminal signals in milliseconds by using glutamate as a neurotransmitter. These synaptically connected enteroendocrine cells are referred to henceforth as neuropod cells. The neuroepithelial circuit they form connects the intestinal lumen to the brainstem in one synapse, opening a physical conduit for the brain to sense gut stimuli with the temporal precision and topographical resolution of a synapse.}, } @article {pmid30237324, year = {2018}, author = {Haupaix, N and Curantz, C and Bailleul, R and Beck, S and Robic, A and Manceau, M}, title = {The periodic coloration in birds forms through a prepattern of somite origin.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aar4777}, pmid = {30237324}, issn = {1095-9203}, mesh = {Agouti Signaling Protein/genetics ; Animals ; Galliformes/classification/*embryology/genetics/*physiology ; Gene Dosage ; *Skin Pigmentation ; Somites/*physiology ; }, abstract = {The periodic stripes and spots that often adorn animals' coats have been largely viewed as self-organizing patterns, forming through dynamics such as Turing's reaction-diffusion within the developing skin. Whether preexisting positional information also contributes to the periodicity and orientation of these patterns has, however, remained unclear. We used natural variation in colored stripes of juvenile galliform birds to show that stripes form in a two-step process. Autonomous signaling from the somite sets stripe position by forming a composite prepattern marked by the expression profile of agouti Subsequently, agouti regulates stripe width through dose-dependent control of local pigment production. These results reveal that early developmental landmarks can shape periodic patterns upstream of late local dynamics, and thus constrain their evolution.}, } @article {pmid30237323, year = {2018}, author = {}, title = {Erratum for the Report "Precursors of logical reasoning in preverbal human infants" by N. Cesana-Arlotti, A. Martín, E. Téglás, L. Vorobyova, R. Cetnarski, L. L. Bonatti.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aav4136}, pmid = {30237323}, issn = {1095-9203}, } @article {pmid30237322, year = {2018}, author = {García-Bayona, L and Comstock, LE}, title = {Bacterial antagonism in host-associated microbial communities.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aat2456}, pmid = {30237322}, issn = {1095-9203}, support = {R01 AI120633/AI/NIAID NIH HHS/United States ; R01 AI093771/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacterial Infections/microbiology ; Bacterial Secretion Systems ; Bacterial Toxins/metabolism ; Bacteroides/physiology ; Gastrointestinal Microbiome ; Humans ; *Microbial Interactions ; *Microbiota ; Symbiosis ; }, abstract = {Antagonistic interactions are abundant in microbial communities and contribute not only to the composition and relative proportions of their members but also to the longer-term stability of a community. This Review will largely focus on bacterial antagonism mediated by ribosomally synthesized peptides and proteins produced by members of host-associated microbial communities. We discuss recent findings on their diversity, functions, and ecological impacts. These systems play key roles in ecosystem defense, pathogen invasion, spatial segregation, and diversity but also confer indirect gains to the aggressor from products released by killed cells. Investigations into antagonistic bacterial interactions are important for our understanding of how the microbiota establish within hosts, influence health and disease, and offer insights into potential translational applications.}, } @article {pmid30237321, year = {2018}, author = {Slimak, L and Fietzke, J and Geneste, JM and Ontañón, R}, title = {Comment on "U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aau1371}, pmid = {30237321}, issn = {1095-9203}, mesh = {Archaeology ; Carbonates ; *Caves ; Fossils ; *Neanderthals ; }, abstract = {Hoffmann et al (Reports, 23 February 2018, p. 912) report the discovery of parietal art older than 64,800 years and attributed to Neanderthals, at least 25 millennia before the oldest parietal art ever found. Instead, critical evaluation of their geochronological data seems to provide stronger support for an age of 47,000 years, which is much more consistent with the archaeological background in hand.}, } @article {pmid30237320, year = {2018}, author = {Jalal, H and Buchanich, JM and Roberts, MS and Balmert, LC and Zhang, K and Burke, DS}, title = {Changing dynamics of the drug overdose epidemic in the United States from 1979 through 2016.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {}, doi = {10.1126/science.aau1184}, pmid = {30237320}, issn = {1095-9203}, support = {KL2 TR001856/TR/NCATS NIH HHS/United States ; }, mesh = {Analgesics, Opioid/administration & dosage ; Cause of Death ; Demography ; Drug Overdose/*epidemiology/mortality ; Epidemics ; Humans ; Substance-Related Disorders/epidemiology ; Time Factors ; United States/epidemiology ; }, abstract = {Better understanding of the dynamics of the current U.S. overdose epidemic may aid in the development of more effective prevention and control strategies. We analyzed records of 599,255 deaths from 1979 through 2016 from the National Vital Statistics System in which accidental drug poisoning was identified as the main cause of death. By examining all available data on accidental poisoning deaths back to 1979 and showing that the overall 38-year curve is exponential, we provide evidence that the current wave of opioid overdose deaths (due to prescription opioids, heroin, and fentanyl) may just be the latest manifestation of a more fundamental longer-term process. The 38+ year smooth exponential curve of total U.S. annual accidental drug poisoning deaths is a composite of multiple distinctive subepidemics of different drugs (primarily prescription opioids, heroin, methadone, synthetic opioids, cocaine, and methamphetamine), each with its own specific demographic and geographic characteristics.}, } @article {pmid30237288, year = {2018}, author = {O'Neill, EM and Mucyn, TS and Patteson, JB and Finkel, OM and Chung, EH and Baccile, JA and Massolo, E and Schroeder, FC and Dangl, JL and Li, B}, title = {Phevamine A, a small molecule that suppresses plant immune responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9514-E9522}, pmid = {30237288}, issn = {1091-6490}, support = {R00 GM099904/GM/NIGMS NIH HHS/United States ; R01 GM112739/GM/NIGMS NIH HHS/United States ; T32 GM008500/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/*immunology/microbiology ; Plant Diseases/*immunology/microbiology ; *Plant Immunity ; Pseudomonas syringae/genetics/*metabolism ; Virulence Factors/genetics/*metabolism ; }, abstract = {Bacterial plant pathogens cause significant crop damage worldwide. They invade plant cells by producing a variety of virulence factors, including small-molecule toxins and phytohormone mimics. Virulence of the model pathogen Pseudomonas syringae pv. tomato DC3000 (Pto) is regulated in part by the sigma factor HrpL. Our study of the HrpL regulon identified an uncharacterized, three-gene operon in Pto that is controlled by HrpL and related to the Erwinia hrp-associated systemic virulence (hsv) operon. Here, we demonstrate that the hsv operon contributes to the virulence of Pto on Arabidopsis thaliana and suppresses bacteria-induced immune responses. We show that the hsv-encoded enzymes in Pto synthesize a small molecule, phevamine A. This molecule consists of l-phenylalanine, l-valine, and a modified spermidine, and is different from known small molecules produced by phytopathogens. We show that phevamine A suppresses a potentiation effect of spermidine and l-arginine on the reactive oxygen species burst generated upon recognition of bacterial flagellin. The hsv operon is found in the genomes of divergent bacterial genera, including ∼37% of P. syringae genomes, suggesting that phevamine A is a widely distributed virulence factor in phytopathogens. Our work identifies a small-molecule virulence factor and reveals a mechanism by which bacterial pathogens overcome plant defense. This work highlights the power of omics approaches in identifying important small molecules in bacteria-host interactions.}, } @article {pmid30237287, year = {2018}, author = {Piaggi, PM and Parrinello, M}, title = {Predicting polymorphism in molecular crystals using orientational entropy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10251-10256}, pmid = {30237287}, issn = {1091-6490}, abstract = {We introduce a computational method to discover polymorphs in molecular crystals at finite temperature. The method is based on reproducing the crystallization process starting from the liquid and letting the system discover the relevant polymorphs. This idea, however, conflicts with the fact that crystallization has a timescale much longer than that of molecular simulations. To bring the process within affordable simulation time, we enhance the fluctuations of a collective variable by constructing a bias potential with well-tempered metadynamics. We use as a collective variable an entropy surrogate based on an extended pair correlation function that includes the correlation between the orientations of pairs of molecules. We also propose a similarity metric between configurations based on the extended pair correlation function and a generalized Kullback-Leibler divergence. In this way, we automatically classify the configurations as belonging to a given polymorph, using our metric and a hierarchical clustering algorithm. We apply our method to urea and naphthalene. We find different polymorphs for both substances, and one of them is stabilized at finite temperature by entropic effects.}, } @article {pmid30237286, year = {2018}, author = {Holmes, DF and Yeung, CC and Garva, R and Zindy, E and Taylor, SH and Lu, Y and Watson, S and Kalson, NS and Kadler, KE}, title = {Synchronized mechanical oscillations at the cell-matrix interface in the formation of tensile tissue.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9288-E9297}, pmid = {30237286}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 110126/Z/15/Z//Wellcome Trust/United Kingdom ; 203128/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Cell Membrane/*metabolism ; Extracellular Matrix/*metabolism ; Fibroblasts/*metabolism ; Humans ; *Stress, Mechanical ; *Tensile Strength ; }, abstract = {The formation of uniaxial fibrous tissues with defined viscoelastic properties implies the existence of an orchestrated mechanical interaction between the cytoskeleton and the extracellular matrix. This study addresses the nature of this interaction. The hypothesis is that this mechanical interplay underpins the mechanical development of the tissue. In embryonic tendon tissue, an early event in the development of a mechanically robust tissue is the interaction of the pointed tips of extracellular collagen fibrils with the fibroblast plasma membrane to form stable interface structures (fibripositors). Here, we used a fibroblast-generated tissue that is structurally and mechanically matched to embryonic tendon to demonstrate homeostasis of cell-derived and external strain-derived tension over repeated cycles of strain and relaxation. A cell-derived oscillatory tension component is evident in this matrix construct. This oscillatory tension involves synchronization of individual cell forces across the construct and is induced in each strain cycle by transient relaxation and transient tensioning of the tissue. The cell-derived tension along with the oscillatory component is absent in the presence of blebbistatin, which disrupts actinomyosin force generation of the cell. The time period of this oscillation (60-90 s) is well-defined in each tissue sample and matches a primary viscoelastic relaxation time. We hypothesize that this mechanical oscillation of fibroblasts with plasma membrane anchored collagen fibrils is a key factor in mechanical sensing and feedback regulation in the formation of tensile tissues.}, } @article {pmid30237285, year = {2018}, author = {Wang, Y and Verma, P and Jin, X and Truhlar, DG and He, X}, title = {Revised M06 density functional for main-group and transition-metal chemistry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10257-10262}, pmid = {30237285}, issn = {1091-6490}, abstract = {We present a hybrid metageneralized-gradient-approximation functional, revM06, which is based on adding Hartree-Fock exchange to the revM06-L functional form. Compared with the original M06 suite of density functionals, the resulting revM06 functional has significantly improved across-the-board accuracy for both main-group and transition-metal chemistry. The revM06 functional improves on the M06-2X functional for main-group and transition-metal bond energies, atomic excitation energies, isomerization energies of large molecules, molecular structures, and both weakly and strongly correlated atomic and molecular data, and it shows a clear improvement over M06 and M06-2X for noncovalent interactions, including smoother potential curves for rare-gas dimers. The revM06 functional also predicts more accurate results than M06 and M06-2X for most of the outside-the-training-set test sets examined in this study. Therefore, the revM06 functional is well-suited for a broad range of chemical applications for both main-group and transition-metal elements.}, } @article {pmid30237284, year = {2018}, author = {Nguyen, T and Su, C and Singh, M}, title = {Let-7i inhibition enhances progesterone-induced functional recovery in a mouse model of ischemia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9668-E9677}, pmid = {30237284}, issn = {1091-6490}, support = {P01 AG027956/AG/NIA NIH HHS/United States ; T32 AG020494/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/metabolism/pathology ; Brain Ischemia/drug therapy/*metabolism/pathology ; Brain-Derived Neurotrophic Factor/metabolism ; Cerebral Cortex/*metabolism/pathology ; Disease Models, Animal ; Membrane Proteins/metabolism ; Mice ; MicroRNAs/*antagonists & inhibitors/metabolism ; Neuroprotective Agents/*pharmacology ; Progesterone/*pharmacology ; Receptors, Progesterone/metabolism ; Recovery of Function/*drug effects ; }, abstract = {Progesterone (P4) is a potent neuroprotectant and a promising therapeutic for stroke treatment. However, the underlying mechanism(s) remain unclear. Our laboratory recently reported that brain-derived neurotrophic factor (BDNF) is a critical mediator of P4's protective actions and that P4-induced BDNF release from cortical astrocytes is mediated by a membrane-associated progesterone receptor, Pgrmc1. Here, we report that the microRNA (miRNA) let-7i is a negative regulator of Pgrmc1 and BDNF in glia and that let-7i disrupts P4-induced BDNF release and P4's beneficial effects on cell viability and markers of synaptogenesis. Using an in vivo model of ischemia, we demonstrate that inhibiting let-7i enhances P4-induced neuroprotection and facilitates functional recovery following stroke. The discovery of such factors that regulate the cytoprotective effects of P4 may lead to the development of biomarkers to differentiate/predict those likely to respond favorably to P4 versus those that do not.}, } @article {pmid30237283, year = {2018}, author = {Bennett, DIG and Fleming, GR and Amarnath, K}, title = {Energy-dependent quenching adjusts the excitation diffusion length to regulate photosynthetic light harvesting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9523-E9531}, pmid = {30237283}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Light ; Light-Harvesting Protein Complexes/*chemistry/metabolism ; *Models, Chemical ; }, abstract = {An important determinant of crop yields is the regulation of photosystem II (PSII) light harvesting by energy-dependent quenching (qE). However, the molecular details of excitation quenching have not been quantitatively connected to the fraction of excitations converted to chemical energy by PSII reaction centers (PSII yield), which determines flux to downstream metabolism. Here, we incorporate excitation dissipation by qE into a pigment-scale model of excitation transfer and trapping for a 200 × 200-nm patch of the grana membrane. We show that excitation transport can be rigorously coarse grained to a 2D random walk with an excitation diffusion length determined by the extent of quenching. We present an alternative method for analyzing pulse amplitude-modulated chlorophyll fluorescence measurements that incorporates the effects of a variable excitation diffusion length during qE activation.}, } @article {pmid30237247, year = {2018}, author = {Evans, RE and Bhaskar, MK and Sukachev, DD and Nguyen, CT and Sipahigil, A and Burek, MJ and Machielse, B and Zhang, GH and Zibrov, AS and Bielejec, E and Park, H and Lončar, M and Lukin, MD}, title = {Photon-mediated interactions between quantum emitters in a diamond nanocavity.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {662-665}, doi = {10.1126/science.aau4691}, pmid = {30237247}, issn = {1095-9203}, abstract = {Photon-mediated interactions between quantum systems are essential for realizing quantum networks and scalable quantum information processing. We demonstrate such interactions between pairs of silicon-vacancy (SiV) color centers coupled to a diamond nanophotonic cavity. When the optical transitions of the two color centers are tuned into resonance, the coupling to the common cavity mode results in a coherent interaction between them, leading to spectrally resolved superradiant and subradiant states. We use the electronic spin degrees of freedom of the SiV centers to control these optically mediated interactions. Such controlled interactions will be crucial in developing cavity-mediated quantum gates between spin qubits and for realizing scalable quantum network nodes.}, } @article {pmid30237246, year = {2018}, author = {Yamashiro, C and Sasaki, K and Yabuta, Y and Kojima, Y and Nakamura, T and Okamoto, I and Yokobayashi, S and Murase, Y and Ishikura, Y and Shirane, K and Sasaki, H and Yamamoto, T and Saitou, M}, title = {Generation of human oogonia from induced pluripotent stem cells in vitro.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {356-360}, doi = {10.1126/science.aat1674}, pmid = {30237246}, issn = {1095-9203}, mesh = {Cellular Reprogramming Techniques/*methods ; DNA Methylation ; Epigenesis, Genetic ; Female ; Humans ; Induced Pluripotent Stem Cells/*cytology ; *Oogenesis ; Oogonia/*cytology ; Ovary/*growth & development ; }, abstract = {Human in vitro gametogenesis may transform reproductive medicine. Human pluripotent stem cells (hPSCs) have been induced into primordial germ cell-like cells (hPGCLCs); however, further differentiation to a mature germ cell has not been achieved. Here, we show that hPGCLCs differentiate progressively into oogonia-like cells during a long-term in vitro culture (approximately 4 months) in xenogeneic reconstituted ovaries with mouse embryonic ovarian somatic cells. The hPGCLC-derived oogonia display hallmarks of epigenetic reprogramming-genome-wide DNA demethylation, imprint erasure, and extinguishment of aberrant DNA methylation in hPSCs-and acquire an immediate precursory state for meiotic recombination. Furthermore, the inactive X chromosome shows a progressive demethylation and reactivation, albeit partially. These findings establish the germline competence of hPSCs and provide a critical step toward human in vitro gametogenesis.}, } @article {pmid30237245, year = {2018}, author = {Zhao, S and Gensch, T and Murray, B and Niemeyer, ZL and Sigman, MS and Biscoe, MR}, title = {Enantiodivergent Pd-catalyzed C-C bond formation enabled through ligand parameterization.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6415}, pages = {670-674}, doi = {10.1126/science.aat2299}, pmid = {30237245}, issn = {1095-9203}, support = {SC1 GM110010/GM/NIGMS NIH HHS/United States ; }, abstract = {Despite the enormous potential for the use of stereospecific cross-coupling reactions to rationally manipulate the three-dimensional structure of organic molecules, the factors that control the transfer of stereochemistry in these reactions remain poorly understood. Here we report a mechanistic and synthetic investigation into the use of enantioenriched alkylboron nucleophiles in stereospecific Pd-catalyzed Suzuki cross-coupling reactions. By developing a suite of molecular descriptors of phosphine ligands, we could apply predictive statistical models to select or design distinct ligands that respectively promoted stereoinvertive and stereoretentive cross-coupling reactions. Stereodefined branched structures were thereby accessed through the predictable manipulation of absolute stereochemistry, and a general model for the mechanism of alkylboron transmetallation was proposed.}, } @article {pmid30237040, year = {2018}, author = {Oborník, M}, title = {The Birth of Red Complex Plastids: One, Three, or Four Times?.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {923-925}, doi = {10.1016/j.pt.2018.09.001}, pmid = {30237040}, issn = {1471-5007}, mesh = {Apicomplexa ; Cell Cycle ; *Plastids ; *Symbiosis ; }, } @article {pmid30236627, year = {2018}, author = {Proffitt, T and Haslam, M and Mercader, JF and Boesch, C and Luncz, LV}, title = {Revisiting Panda 100, the first archaeological chimpanzee nut-cracking site.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {117-139}, doi = {10.1016/j.jhevol.2018.04.016}, pmid = {30236627}, issn = {1095-8606}, abstract = {Archaeological recovery of chimpanzee Panda oleosa nut cracking tools at the Panda 100 (P100) and Noulo sites in the Taï Forest, Côte d'Ivoire, showed that this behavior is over 4000 years old, making it the oldest known evidence of non-human tool use. In 2002, the first report on the lithic material from P100 was directly compared to early hominin stone tools, highlighting their similarities and proposing the name 'Pandan' for the chimpanzee material. Here we present an expanded and comprehensive technological, microscopic, and refit analysis of the late twentieth century lithic assemblage from P100. Our re-analysis provides new data and perspectives on the applicability of chimpanzee nut cracking tools to our understanding of the percussive behaviors of early hominins. We identify several new refit sets, including the longest (>17 m) hammerstone transport seen in the chimpanzee archaeological record. We provide detailed evidence of the fragmentation sequences of Panda nut hammerstones, and characterize the percussive damage on fragmented material from P100. Finally, we emphasize that the chimpanzee lithic archaeological record is dynamic, with the preservation of actual hammerstones being rare, and the preservation of small broken pieces more common. P100 - the first archaeological chimpanzee nut cracking lithic assemblage - provides a valuable comparative sample by which to identify past chimpanzee behavior elsewhere, as well as similar hominin percussive behavior in the Early Stone Age.}, } @article {pmid30236446, year = {2018}, author = {Hou, W and Jerome-Majewska, LA}, title = {TMED2/emp24 is required in both the chorion and the allantois for placental labyrinth layer development.}, journal = {Developmental biology}, volume = {444}, number = {1}, pages = {20-32}, doi = {10.1016/j.ydbio.2018.09.012}, pmid = {30236446}, issn = {1095-564X}, abstract = {TMED2, a member of the transmembrane emp24 domain (TMED) family, is required for transport of cargo proteins between the ER and Golgi. TMED2 is also important for normal morphogenesis of mouse embryos and their associated placenta, and in fact Tmed2 homozygous mutant embryos arrest at mid-gestation due to a failure of placental labyrinth layer formation. Differentiation of the placental labyrinth layer depends on chorioallantoic attachment (contact between the chorion and allantois), and branching morphogenesis (mingling of cells from these two tissues). Since Tmed2 mRNA was found in both the chorion and allantois, and 50% of Tmed2 homozygous mutant embryos failed to undergo chorioallantoic attachment, the tissue-specific requirement of Tmed2 during placental labyrinth layer formation remained a mystery. Herein, we report differential localization of TMED2 protein in the chorion and allantois, abnormal ER retention of Fibronectin in Tmed2 homozygous mutant allantoises and cell-autonomous requirement for Tmed2 in the chorion for chorioallantoic attachment and fusion. Using an ex vivo model of explanted chorions and allantoises, we showed that chorioallantoic attachment failed to occur in 50% of samples when homozygous mutant chorions were recombined with wild type allantoises. Furthermore, though expression of genes associated with trophoblast differentiation was maintained in Tmed2 mutant chorions with chorioallantoic attachment, expression of these genes was attenuated. In addition, Tmed2 homozygous mutant allantoises could undergo branching morphogenesis, however the region of mixing between mutant and wild type cells was reduced, and expression of genes associated with trophoblast differentiation was also attenuated. Our data also suggest that Fibronectin is a cargo protein of TMED2 and indicates that Tmed2 is required cell-autonomously and non-autonomously in the chorion and the allantois for placental labyrinth layer formation.}, } @article {pmid30236445, year = {2018}, author = {Tani-Matsuhana, S and Vieceli, FM and Gandhi, S and Inoue, K and Bronner, ME}, title = {Transcriptome profiling of the cardiac neural crest reveals a critical role for MafB.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.09.015}, pmid = {30236445}, issn = {1095-564X}, support = {R01 DE024157/DE/NIDCR NIH HHS/United States ; R01 HL140587/HL/NHLBI NIH HHS/United States ; }, abstract = {The cardiac neural crest originates in the caudal hindbrain, migrates to the heart, and contributes to septation of the cardiac outflow tract and ventricles, an ability unique to this neural crest subpopulation. Here we have used a FoxD3 neural crest enhancer to isolate a pure population of cardiac neural crest cells for transcriptome analysis. This has led to the identification of transcription factors, signaling receptors/ligands, and cell adhesion molecules upregulated in the early migrating cardiac neural crest. We then functionally tested the role of one of the upregulated transcription factors, MafB, and found that it acts as a regulator of Sox10 expression specifically in the cardiac neural crest. Our results not only reveal the genome-wide profile of early migrating cardiac neural crest cells, but also provide molecular insight into what makes the cardiac neural crest unique.}, } @article {pmid30236158, year = {2018}, author = {Xun, W and Yan, R and Ren, Y and Jin, D and Xiong, W and Zhang, G and Cui, Z and Xin, X and Zhang, R}, title = {Grazing-induced microbiome alterations drive soil organic carbon turnover and productivity in meadow steppe.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {170}, pmid = {30236158}, issn = {2049-2618}, abstract = {BACKGROUND: Grazing is a major modulator of biodiversity and productivity in grasslands. However, our understanding of grazing-induced changes in below-ground communities, processes, and soil productivity is limited. Here, using a long-term enclosed grazing meadow steppe, we investigated the impacts of grazing on the soil organic carbon (SOC) turnover, the microbial community composition, resistance and activity under seasonal changes, and the microbial contributions to soil productivity.

RESULTS: The results demonstrated that grazing had significant impacts on soil microbial communities and ecosystem functions in meadow steppe. The highest microbial α-diversity was observed under light grazing intensity, while the highest β-diversity was observed under moderate grazing intensity. Grazing shifted the microbial composition from fungi dominated to bacteria dominated and from slow growing to fast growing, thereby resulting in a shift from fungi-dominated food webs primarily utilizing recalcitrant SOC to bacteria-dominated food webs mainly utilizing labile SOC. Moreover, the higher fungal recalcitrant-SOC-decomposing activities and bacterial labile-SOC-decomposing activities were observed in fungi- and bacteria-dominated communities, respectively. Notably, the robustness of bacterial community and the stability of bacterial activity were associated with α-diversity, while this was not the case for the robustness of fungal community and its associated activities. Finally, we observed that microbial α-diversity rather than SOC turnover rate can predict soil productivity.

CONCLUSIONS: Our findings indicate the strong influence of grazing on soil microbial community, SOC turnover, and soil productivity and the important positive role of soil microbial α-diversity in steering the functions of meadow steppe ecosystems.}, } @article {pmid30236109, year = {2018}, author = {Stringer, JM and Forster, SC and Qu, Z and Prokopuk, L and O'Bryan, MK and Gardner, DK and White, SJ and Adelson, D and Western, PS}, title = {Reduced PRC2 function alters male germline epigenetic programming and paternal inheritance.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {104}, pmid = {30236109}, issn = {1741-7007}, support = {098051//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Defining the mechanisms that establish and regulate the transmission of epigenetic information from parent to offspring is critical for understanding disease heredity. Currently, the molecular pathways that regulate epigenetic information in the germline and its transmission to offspring are poorly understood.

RESULTS: Here we provide evidence that Polycomb Repressive Complex 2 (PRC2) regulates paternal inheritance. Reduced PRC2 function in mice resulted in male sub-fertility and altered epigenetic and transcriptional control of retrotransposed elements in foetal male germ cells. Males with reduced PRC2 function produced offspring that over-expressed retrotransposed pseudogenes and had altered preimplantation embryo cleavage rates and cell cycle control.

CONCLUSION: This study reveals a novel role for the histone-modifying complex, PRC2, in paternal intergenerational transmission of epigenetic effects on offspring, with important implications for understanding disease inheritance.}, } @article {pmid30236094, year = {2018}, author = {Polidori, C and Nucifora, M and Sánchez-Fernández, D}, title = {Environmental niche unfilling but limited options for range expansion by active dispersion in an alien cavity-nesting wasp.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {36}, pmid = {30236094}, issn = {1472-6785}, support = {SECTI contract//Universidad de Castilla-La Mancha/International ; CGL2017-83046-P//Ministerio de Economía, Industria y Competitividad, Gobierno de España/International ; }, abstract = {BACKGROUND: Predicting the patterns of range expansion of alien species is central to develop effective strategies for managing potential biological invasions. Here, we present a study on the potential distribution of the American cavity-nesting, Orthoptera-hunting and solitary wasp, Isodontia mexicana (Hymenoptera: Sphecidae), which was first detected as alien species in France in 1960 and now is present in many European countries. After having updated its current distribution, we estimated the environmental space (based on bioclimatic data and altitude) occupied by the species and subsequently predicted its environmental potential distribution under both present and future climatic conditions at global scale.

RESULTS: The wasp lives in low-altitude areas of the Northern hemisphere with moderate temperatures and precipitation. The environmental space occupied in the invaded area is practically just a subset (42%) of that occupied in the native area, showing a process of environmental niche unfilling (i.e. the species only partially fills its environmental niche in the invaded range). Besides, I. mexicana could also live in other temperate areas, mainly in the Southern hemisphere, particularly close to the coasts. However, geographic (oceans) and/or climatic (tropical areas, mountain chains) barriers would prevent the species to reach these potential areas unless through human trade activity. The species could thus only reach, by active dispersion, the remaining invadable areas of Europe. Estimations for the future (2050 and 2070) predict an expansion through active dispersion towards North in the native range and towards North and East in the invaded range, but future conditions would not break down the current climatic barriers in the Southern hemisphere.

CONCLUSIONS: Isodontia mexicana has not shifted its environmental niche in the invaded area. It could still occupy some new areas by active dispersion, but confined to Europe. The conspicuous niche unfilling shown by this wasp species could reflect the likely single introduction in Europe just a few decades ago. Furthermore, results stay in line with other studies that found niche unfilling rather than niche expansion in insects.}, } @article {pmid30236061, year = {2018}, author = {Xiao, W and Ye, Z and Yao, X and He, L and Lei, Y and Luo, D and Su, S}, title = {Evolution of ALOG gene family suggests various roles in establishing plant architecture of Torenia fournieri.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {204}, pmid = {30236061}, issn = {1471-2229}, support = {2014ZX0800943B//Ministry of Agriculture of the People's Republic of China/ ; 2013BAD01B0702//Ministry of Science and Technology of the People's Republic of China/ ; }, mesh = {Bacterial Proteins/genetics/metabolism ; *Evolution, Molecular ; Gene Duplication ; Gene Expression Regulation, Plant ; Lamiales/genetics/*physiology ; Luminescent Proteins/genetics/metabolism ; Multigene Family ; Phenotype ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified ; RNA-Binding Proteins/*genetics/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; }, abstract = {BACKGROUND: ALOG (Arabidopsis LSH1 and Oryza G1) family with a conserved domain widely exists in plants. A handful of ALOG members have been functionally characterized, suggesting their roles as key developmental regulators. However, the evolutionary scenario of this gene family during the diversification of plant species remains largely unclear.

METHODS: Here, we isolated seven ALOG genes from Torenia fournieri and phylogenetically analyzed them with different ALOG members from representative plants in major taxonomic clades. We further examined their gene expression patterns by RT-PCR, and regarding the protein subcellular localization, we co-expressed the candidates with a nuclear marker. Finally, we explored the functional diversification of two ALOG members, TfALOG1 in euALOG1 and TfALOG2 in euALOG4 sub-clades by obtaining the transgenic T. fournieri plants.

RESULTS: The ALOG gene family can be divided into different lineages, indicating that extensive duplication events occurred within eudicots, grasses and bryophytes, respectively. In T. fournieri, seven TfALOG genes from four sub-clades exhibit distinct expression patterns. TfALOG1-6 YFP-fused proteins were accumulated in the nuclear region, while TfALOG7-YFP was localized both in nuclear and cytoplasm, suggesting potentially functional diversification. In the 35S:TfALOG1 transgenic lines, normal development of petal epidermal cells was disrupted, accompanied with changes in the expression of MIXTA-like genes. In 35S:TfALOG2 transgenic lines, the leaf mesophyll cells development was abnormal, favoring functional differences between the two homologous proteins. Unfortunately, we failed to observe any phenotypical changes in the TfALOG1 knock-out mutants, which might be due to functional redundancy as the case in Arabidopsis.

CONCLUSION: Our results unraveled the evolutionary history of ALOG gene family, supporting the idea that changes occurred in the cis regulatory and/or nonconserved coding regions of ALOG genes may result in new functions during the establishment of plant architecture.}, } @article {pmid30236060, year = {2018}, author = {Wang, Z and Zhu, T and Ma, W and Wang, N and Qu, G and Zhang, S and Wang, J}, title = {Genome-wide analysis of long non-coding RNAs in Catalpa bungei and their potential function in floral transition using high-throughput sequencing.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {86}, pmid = {30236060}, issn = {1471-2156}, support = {201504101//Forestry Industry Research Special Funds for Public Welfare Projects/ ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) have crucial roles in various biological regulatory processes. However, the study of lncRNAs is limited in woody plants. Catalpa bungei is a valuable ornamental tree with a long cultivation history in China, and a deeper understanding of the floral transition mechanism in C. bungei would be interesting from both economic and scientific perspectives.

RESULTS: In this study, we categorized C. bungei buds from early flowering (EF) and normal flowering (NF) varieties into three consecutive developmental stages. These buds were used to systematically study lncRNAs during floral transition using high-throughput sequencing to identify molecular regulatory networks. Quantitative real-time PCR was performed to study RNA expression changes in different stages. In total, 12,532 lncRNAs and 26,936 messenger RNAs (mRNAs) were detected. Moreover, 680 differentially expressed genes and 817 differentially expressed lncRNAs were detected during the initiation of floral transition. The results highlight the mRNAs and lncRNAs that may be involved in floral transition, as well as the many lncRNAs serving as microRNA precursors. We predicted the functions of lncRNAs by analysing the relationships between lncRNAs and mRNAs. Seven lncRNA-mRNA interaction pairs may participate in floral transition.

CONCLUSIONS: This study is the first to identify lncRNAs and their potential functions in floral transition, providing a starting point for detailed determination of the functions of lncRNAs in C. bungei.}, } @article {pmid30236059, year = {2018}, author = {Orsucci, M and Audiot, P and Nidelet, S and Dorkeld, F and Pommier, A and Vabre, M and Severac, D and Rohmer, M and Gschloessl, B and Streiff, R}, title = {Transcriptomic response of female adult moths to host and non-host plants in two closely related species.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {145}, pmid = {30236059}, issn = {1471-2148}, support = {ANR-13-BSV7-0012-01//Agence Nationale de la Recherche (FR)/International ; PhD grant//Université de Montpellier/International ; }, mesh = {Adaptation, Physiological/genetics ; Animals ; Female ; Gene Expression Profiling ; Linear Models ; Male ; Molecular Sequence Annotation ; Moths/*genetics ; Plants/*parasitology ; Principal Component Analysis ; Species Specificity ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Divergent selection has been shown to promote speciation in many taxa and especially in phytophagous insects. In the Ostrinia species complex, the European corn borer (ECB) and adzuki bean borer (ABB) are two sibling species specialized to different host plants. The first is a well-known maize pest, whereas the second is a polyphagous species associated with various dicotyledons. Their specialization to host plants is driven by morphological, behavioral and physiological adaptations. In particular, previous studies have shown that ECB and ABB display marked behavior with regard to plant choice during oviposition, involving specific preference and avoidance mechanisms. In this study, our goal was to identify the mechanisms underlying this host-plant specialization in adult females through an analysis of their gene expression. We assembled and annotated a de novo reference transcriptome and measured differences in gene expression between ECB and ABB females, and between environments. We related differentially expressed genes to host preference behavior, and highlighted the functional categories involved. We also conducted a specific analysis of chemosensory genes, which are considered to be good candidates for host recognition before oviposition.

RESULTS: We recorded more differentially expressed genes in ECB than in ABB samples, and noticed that the majority of genes potentially involved in the host preference were different between the two species. At the functional level, the response to plant environment in adult females involved many processes, including the metabolism of carbohydrates, lipids, proteins, and amino acids; detoxification mechanisms and immunity; and the chemosensory repertoire (as expected). Until now, most of the olfactory receptors described in Ostrinia spp. had been tested for their putative role in pheromone recognition by males. Here we observed that one specific olfactory receptor was clearly associated with ECB's discrimination between maize and mugwort conditions, highlighting a potential new candidate involved in plant odor discrimination in adult females.

CONCLUSIONS: Our results are a first step toward the identification of candidate genes and functions involved in chemosensory processes, carbohydrate metabolism, and virus and retrovirus dynamics. These candidates provide new avenues for research into understanding the role of divergent selection between different environments in species diversification.}, } @article {pmid30236058, year = {2018}, author = {Van Oosten, MJ and Di Stasio, E and Cirillo, V and Silletti, S and Ventorino, V and Pepe, O and Raimondi, G and Maggio, A}, title = {Root inoculation with Azotobacter chroococcum 76A enhances tomato plants adaptation to salt stress under low N conditions.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {205}, pmid = {30236058}, issn = {1471-2229}, support = {FP7-KBBE-2012-6//Horizon 2020/ ; 727929//Horizon 2020/ ; }, mesh = {Adaptation, Physiological/*physiology ; Azotobacter/growth & development/*physiology ; Gene Expression Regulation, Plant ; Lycopersicon esculentum/microbiology/*physiology ; Nitrogen/*metabolism ; Plant Leaves/physiology ; Plant Roots/*microbiology ; Rhizosphere ; Salt Tolerance ; Symbiosis ; }, abstract = {BACKGROUND: The emerging roles of rhizobacteria in improving plant nutrition and stress protection have great potential for sustainable use in saline soils. We evaluated the function of the salt-tolerant strain Azotobacter chroococcum 76A as stress protectant in an important horticultural crop, tomato. Specifically we hypothesized that treatment of tomato plants with A. chroococcum 76A could improve plant performance under salinity stress and sub-optimal nutrient regimen.

RESULTS: Inoculation of Micro Tom tomato plants with A. chroococcum 76A increased numerous growth parameters and also conferred protective effects under both moderate (50 mM NaCl) and severe (100 mM NaCl) salt stresses. These benefits were mostly observed under reduced nutrient regimen and were less appreciable in optimal nitrogen conditions. Therefore, the efficiency of A. chroococcum 76A was found to be dependent on the nutrient status of the rhizosphere. The expression profiles of LEA genes indicated that A. chroococcum 76A treated plants were more responsive to stress stimuli when compared to untreated controls. However, transcript levels of key nitrogen assimilation genes revealed that the optimal nitrogen regimen, in combination with the strain A. chroococcum 76A, may have saturated plant's ability to assimilate nitrogen.

CONCLUSIONS: Roots inoculation with A. chroococcum 76A tomato promoted tomato plant growth, stress tolerance and nutrient assimilation efficiency under moderate and severe salinity. Inoculation with beneficial bacteria such as A. chroococcum 76A may be an ideal solution for low-input systems, where environmental constraints and limited chemical fertilization may affect the potential yield.}, } @article {pmid30236057, year = {2018}, author = {Wanka, KM and Damerau, T and Costas, B and Krueger, A and Schulz, C and Wuertz, S}, title = {Isolation and characterization of native probiotics for fish farming.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {119}, pmid = {30236057}, issn = {1471-2180}, abstract = {BACKGROUND: Innovations in fish nutrition act as drivers for the sustainable development of the rapidly expanding aquaculture sector. Probiotic dietary supplements are able to improve health and nutrition of livestock, but respective bacteria have mainly been isolated from terrestrial, warm-blooded hosts, limiting an efficient application in fish. Native probiotics adapted to the gastrointestinal tract of the respective fish species will establish within the original host more efficiently.

RESULTS: Here, 248 autochthonous isolates were cultured from the digestive system of three temperate flatfish species. Upon 16S rRNA gene sequencing of 195 isolates, 89.7% (n = 175) Gram-negatives belonging to the Alpha- (1.0%), Beta- (4.1%) and Gammaproteobacteria (84.6%) were identified. Candidate probiotics were further characterized using in vitro assays addressing 1) inhibition of pathogens, 2) degradation of plant derived anti-nutrient (saponin) and 3) the content of essential fatty acids (FA) and their precursors. Twelve isolates revealed an inhibition towards the common fish pathogen Tenacibaculum maritimum, seven were able to metabolize saponin as sole carbon and energy source and two isolates 012 Psychrobacter sp. and 047 Paracoccus sp. revealed remarkably high contents of docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). Furthermore, a rapid and cost-effective method to coat feed pellets revealed high viability of the supplemented probiotics over 54 d of storage at 4°C.

CONCLUSIONS: Here, a strategy for the isolation and characterization of native probiotic candidates is presented that can easily be adapted to other farmed fish species. The simple coating procedure assures viability of probiotics and can thus be applied for the evaluation of probiotic candidates in the future.}, } @article {pmid30236056, year = {2018}, author = {Ma, C and Ji, T}, title = {Detecting differentially expressed genes for syndromes by considering change in mean and dispersion simultaneously.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {330}, pmid = {30236056}, issn = {1471-2105}, support = {1615789//National Science Foundation/ ; }, mesh = {*Bayes Theorem ; Gene Expression Profiling/*methods ; Gene Expression Regulation/*genetics ; Humans ; Syndrome ; }, abstract = {BACKGROUND: Using next-generation sequencing technology to measure gene expression, an empirically intriguing question concerns the identification of differentially expressed genes across treatment groups. Existing methods aim to identify genes whose mean expressions differ among treatment groups by assuming equal dispersion across all groups. For syndromes, however, various combinations of gene expression alterations can result in the same disease, leading to greater heteroscedasticity in the biological replicates in the disease group compared to the normal group. Traditional methods that only consider changes in the mean will fail to fully analyze gene expression in such a scenario. In addition, sequencing technology is relatively expensive; most labs can only afford a few replicates per treatment group, which poses further challenges to reliably estimating the mean and dispersion under each treatment condition.

RESULTS: We designed an empirical Bayes method and a pooled permutation test to simultaneously consider the change in mean and dispersion across treatment groups. We further computed confidence intervals based on Bayes estimates to identify differentially expressed genes that are unique to each disease sample as well as those that are common across all disease samples. We illustrated our method by applying it to gene expression data from a large offspring syndrome experiment, which motivated this study. We compared our method to competing approaches through simulation studies that mimicked the real datasets to demonstrate the effectiveness of our proposed method.

CONCLUSIONS: We will show that, compared to popular methods that only aim to find the difference in the mean, our method can capture greater variation in the disease group to effectively identify differentially expressed genes for syndromes.}, } @article {pmid30236055, year = {2018}, author = {Diaz, F and Allan, CW and Matzkin, LM}, title = {Positive selection at sites of chemosensory genes is associated with the recent divergence and local ecological adaptation in cactophilic Drosophila.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {144}, pmid = {30236055}, issn = {1471-2148}, support = {DEB- 1219387//National Science Foundation/International ; IOS-1557697//National Science Foundation/International ; }, mesh = {Adaptation, Physiological/*genetics ; Analysis of Variance ; Animals ; Codon/genetics ; Drosophila/*genetics ; Drosophila Proteins/genetics ; *Ecology ; Evolution, Molecular ; Female ; *Genes, Insect ; *Genetic Variation ; Geography ; Phylogeny ; Receptors, Odorant/*genetics ; *Selection, Genetic ; }, abstract = {BACKGROUND: Adaptation to new hosts in phytophagous insects often involves mechanisms of host recognition by genes of sensory pathways. Most often the molecular evolution of sensory genes has been explained in the context of the birth-and-death model. The role of positive selection is less understood, especially associated with host adaptation and specialization. Here we aim to contribute evidence for this latter hypothesis by considering the case of Drosophila mojavensis, a species with an evolutionary history shaped by multiple host shifts in a relatively short time scale, and its generalist sister species, D. arizonae.

RESULTS: We used a phylogenetic and population genetic analysis framework to test for positive selection in a subset of four chemoreceptor genes, one gustatory receptor (Gr) and three odorant receptors (Or), for which their expression has been previously associated with host shifts. We found strong evidence of positive selection at several amino acid sites in all genes investigated, most of which exhibited changes predicted to cause functional effects in these transmembrane proteins. A significant portion of the sites identified as evolving positively were largely found in the cytoplasmic region, although a few were also present in the extracellular domains.

CONCLUSIONS: The pattern of substitution observed suggests that some of these changes likely had an effect on signal transduction as well as odorant recognition and protein-protein interactions. These findings support the role of positive selection in shaping the pattern of variation at chemosensory receptors, both during the specialization onto one or a few related hosts, but as well as during the evolution and adaptation of generalist species into utilizing several hosts.}, } @article {pmid30236054, year = {2018}, author = {Lou, D and Wang, H and Yu, D}, title = {The sucrose non-fermenting-1-related protein kinases SAPK1 and SAPK2 function collaboratively as positive regulators of salt stress tolerance in rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {203}, pmid = {30236054}, issn = {1471-2229}, support = {U1702231//NSFC-the United Fund of Yunnan Province/ ; XDA08020203//the Strategic Priority Research Program of the Chinese Academy of Sciences (Class A)/ ; }, mesh = {Chlorophyll/genetics/metabolism ; Gene Expression Regulation, Plant ; Germination ; Mitogen-Activated Protein Kinase 11/genetics/*metabolism ; Mitogen-Activated Protein Kinase 8/genetics/*metabolism ; Mutation ; Oryza/genetics/*physiology ; Osmosis ; Plants, Genetically Modified/genetics ; Potassium/metabolism ; Reactive Oxygen Species/metabolism ; Salt Tolerance/genetics/*physiology ; Seedlings/physiology ; Sodium/metabolism ; }, abstract = {BACKGROUND: The sucrose non-fermenting-1-related protein kinase 2 family (SnRK2s) unifies different abiotic stress signals in plants. To date, the functions of two rice SnRK2s, osmotic stress/ABA-activated protein kinase 1 (SAPK1) and SAPK2, have been unknown. We investigated their roles in response to salt stress by generating loss-of-function lines using the CRISPR/Cas9 system and by overexpressing these proteins in transgenic rice plants.

RESULTS: Expression profiling revealed that SAPK1 and SAPK2 expression were strongly induced by drought, NaCl, and PEG treatment, but not by ABA. SAPK2 expression was highest in the leaves, followed by the roots, whereas SAPK1 was highest expressed in roots followed by leaves. Both proteins were localized to the nucleus and the cytoplasm. Under salt stress, sapk1, sapk2 and, in particular, sapk1/2 mutants, exhibited reduced germination rates, more severe growth inhibition, more distinct chlorosis, reduced chlorophyll contents, and reduced survival rates in comparison with the wild-type plants. In contrast, SAPK1- and SAPK2-overexpression lines had increased germination rates and reduced sensitivities to salt; including mild reductions in growth inhibition, reduced chlorosis, increased chlorophyll contents and improved survival rates in comparison with the wild-type plants. These results suggest that SAPK1 and SAPK2 may function collaboratively as positive regulators of salt stress tolerance at the germination and seedling stages. We also found that SAPK1 and SAPK2 affected the osmotic potential following salt stress by promoting the generation of osmotically active metabolites such as proline. SAPK1 and SAPK2 also improved reactive oxygen species (ROS) detoxification following salt stress by promoting the generation of ROS scavengers such as ascorbic acid, and by increasing the expression levels of proteins such as superoxide dismutase (SOD) and catalase (CAT). SAPK1 and SAPK2 may function collaboratively in reducing Na+ toxicity by affecting the Na+ distribution between roots and shoots, Na+ exclusion from the cytoplasm, and Na+ sequestration into the vacuoles. These effects may be facilitated through the expression of Na+-and K+-homeostasis-related genes.

CONCLUSION: SAPK1 and SAPK2 may function collaboratively as positive regulators of salt stress tolerance at the germination and seedling stages in rice. SAPK1 and SAPK2 may be useful to improve salt tolerance in crop plants.}, } @article {pmid30235947, year = {2018}, author = {Bagozzi, RP and Verbeke, WJMI and Belschak, F and van Poele, M}, title = {Facial Attractiveness as a Function of Athletic Prowess.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918801369}, doi = {10.1177/1474704918801369}, pmid = {30235947}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Analysis of Variance ; Athletes/*psychology ; Athletic Performance/*psychology ; *Beauty ; Child ; *Facial Expression ; Female ; Humans ; Male ; Middle Aged ; Sex Characteristics ; Young Adult ; }, abstract = {We investigate the relationship between facial attractiveness and athletic prowess. We study the connection between subjective facial attractiveness (measured on a 5-point scale of judged facial attractiveness) and athletes by gender and age of respondents. Five age classes were investigated in Studies 1-5: preadolescents (average age: 8.85 years: n = 92), adolescents (average age: 15.8 years; n = 82), young adults (average age: 21.6 years; n = 181), middle-aged adults (average age: 47.5 years; n = 189), and older adults (65 years old; n = 183). The findings show that world-class athletes are perceived as more facially attractive than amateur athletes, with women athletes perceived as more facially attractive than men, and these findings generally occur to a greater extent for female than male respondents. These findings hold for preadolescents, adolescents, young adults, and older adults. However, results were mixed for middle-aged adults where generally amateur athletes were evaluated more attractive than world-class and men athletes more attractive than women.}, } @article {pmid30234478, year = {2018}, author = {Reiner, JE and Jung, T and Lapp, CJ and Siedler, M and Bunk, B and Overmann, J and Gescher, J}, title = {Kyrpidia spormannii sp. nov., a thermophilic, hydrogen-oxidizing, facultative autotroph, isolated from hydrothermal systems at São Miguel Island, and emended description of the genus Kyrpidia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {12}, pages = {3735-3740}, doi = {10.1099/ijsem.0.003037}, pmid = {30234478}, issn = {1466-5034}, mesh = {Azores ; Bacillales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Glycolipids/chemistry ; Hydrothermal Vents/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Portugal ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-positive, rod-shaped, non-motile, spore-forming bacterium, strain EA-1T, was isolated from hydrothermal sediment samples from the Azores (São Miguel, Portugal). 16S rRNA gene sequence analysis of the isolated bacterium revealed a phylogenetic affiliation with the genus Kyrpidia. The sequence similarity of the five 16S rRNA gene copies to its closest relative, Kyrpidia tusciae, ranged from 97.79 to 97.85 %. The in silico estimate of DNA-DNA hybridization was 56.0 %. The dominant fatty acids of the novel isolate were anteiso-C17 : 0 (49.9 %), iso-C17 : 0 (23.0 %) and iso-C16 : 0 (13.3 %), while the quinone detected was menaquinone MK-7. Analysis of polar lipids identified phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and additional unidentified compounds comprising two glycolipids, two phospholipids and two lipids. The presence of meso-diaminopimelic acid in the peptidoglycan and mannose, arabinose and ribose in the cell wall of strain EA-1T were detected. The strain was able to grow heterotrophically as well as autotrophically with carbon dioxide as the sole carbon source and with hydrogen and oxygen as electron donor and acceptor, respectively. Based on its chemotaxonomic, physiological and genomic characteristics, the new strain is considered to represent a novel species within the genus Kyrpidia, for which the name Kyrpidiaspormannii sp. nov. is proposed. The type strain is strain EA-1T (=DSM 106492T=CCOS1194T).}, } @article {pmid30234476, year = {2018}, author = {Mohr, KI and Wolf, C and Nübel, U and Szafrańska, AK and Steglich, M and Hennessen, F and Gemperlein, K and Kämpfer, P and Martin, K and Müller, R and Wink, J}, title = {A polyphasic approach leads to seven new species of the cellulose-decomposing genus Sorangium, Sorangium ambruticinum sp. nov., Sorangium arenae sp. nov., Sorangium bulgaricum sp. nov., Sorangium dawidii sp. nov., Sorangium kenyense sp. nov., Sorangium orientale sp. nov. and Sorangium reichenbachii sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3576-3586}, doi = {10.1099/ijsem.0.003034}, pmid = {30234476}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Cellulose/*metabolism ; DNA, Bacterial/genetics ; Genes, Bacterial ; Myxococcales/*classification ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Seventy-three strains of Sorangium have been isolated from soil samples collected from all over the world. The strains were characterized using a polyphasic approach and phenotypic, genotypic and chemotype analyses clarified their taxonomic relationships. 16S rRNA, xynB1, groEL1, matrix-assisted laser desorption/ioniziation time-of-flight mass spectrometry and API-ZYM analyses were conducted. In addition, from selected representative strains, fatty acids, quinones and phospholipids were analysed. In silico DNA-DNA hybridization and DNA-DNA hybridization against the current type species of Sorangiumcellulosum strain Soce 1871T (DSM 14627T) completed the analyses. Finally, our study revealed seven new species of Sorangium: Sorangium ambruticinum (Soce 176T; DSM 53252T, NCCB 100639T, sequence accession number ERS2488998), Sorangium arenae (Soce 1078T; DSM 105768T, NCCB 100643T, ERS2489002), Sorangium bulgaricum (Soce 321T; DSM 53339T, NCCB 100640T, ERS2488999), Sorangium dawidii (Soce 362T; DSM 105767T, NCCB 100641T, ERS2489000), Sorangium kenyense (Soce 375T; DSM 105741T, NCCB 100642T, ERS2489001), Sorangium orientale (Soce GT47T; DSM 105742T, NCCB 100638T, ERS2501484) and Sorangium reichenbachii (Soce 1828T; DSM 105769T, NCCB 100644T, ERS2489003).}, } @article {pmid30232458, year = {2018}, author = {Latorre, D and Kallweit, U and Armentani, E and Foglierini, M and Mele, F and Cassotta, A and Jovic, S and Jarrossay, D and Mathis, J and Zellini, F and Becher, B and Lanzavecchia, A and Khatami, R and Manconi, M and Tafti, M and Bassetti, CL and Sallusto, F}, title = {T cells in patients with narcolepsy target self-antigens of hypocretin neurons.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {63-68}, doi = {10.1038/s41586-018-0540-1}, pmid = {30232458}, issn = {1476-4687}, abstract = {Narcolepsy is a chronic sleep disorder caused by the loss of neurons that produce hypocretin. The close association with HLA-DQB1*06:02, evidence for immune dysregulation and increased incidence upon influenza vaccination together suggest that this disorder has an autoimmune origin. However, there is little evidence of autoreactive lymphocytes in patients with narcolepsy. Here we used sensitive cellular screens and detected hypocretin-specific CD4+ T cells in all 19 patients that we tested; T cells specific for tribbles homologue 2-another self-antigen of hypocretin neurons-were found in 8 out of 13 patients. Autoreactive CD4+ T cells were polyclonal, targeted multiple epitopes, were restricted primarily by HLA-DR and did not cross-react with influenza antigens. Hypocretin-specific CD8+ T cells were also detected in the blood and cerebrospinal fluid of several patients with narcolepsy. Autoreactive clonotypes were serially detected in the blood of the same-and even of different-patients, but not in healthy control individuals. These findings solidify the autoimmune aetiology of narcolepsy and provide a basis for rapid diagnosis and treatment of this disease.}, } @article {pmid30232457, year = {2018}, author = {Willett, SD and McCoy, SW and Beeson, HW}, title = {Transience of the North American High Plains landscape and its impact on surface water.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {528-532}, doi = {10.1038/s41586-018-0532-1}, pmid = {30232457}, issn = {1476-4687}, support = {NNX15AI02H/NASA/NASA/United States ; }, abstract = {Ecosystem diversity and human activity in dry climates depend not just on the magnitude of rainfall, but also on the landscape's ability to retain water. This is illustrated dramatically in the High Plains of North America, where despite the semi-arid modern and past climate, the hydrologic conditions are diverse. Large rivers sourced in the Rocky Mountains cut through elevated plains that exhibit limited river drainage but widespread surface water in the form of ephemeral (seasonal) playa lakes1, as well as extensive groundwater hosted in the High Plains aquifer of the Ogallala formations2. Here we present a model, with supporting evidence, which shows that the High Plains landscape is currently in a transient state, in which the landscape has bifurcated into an older region with an inefficient river network and a younger, more efficient, river channel network that is progressively cannibalizing the older region. The older landscape represents the remnants of the Ogallala sediments that once covered the entirety of the High Plains, forming depositional fans that buried the pre-existing river network and effectively 'repaved' the High Plains3-6. Today we are witnessing the establishment of a new river network that is dissecting the landscape, capturing channels and eroding these sediment fans. Through quantitative analysis of the geometry of the river network, we show how network reorganization has resulted in a distinctive pattern of erosion, whereby the largest rivers have incised the older surface, removed fan heads near the Rocky Mountains and eroded the fan toes, but left portions of the central fan surface and the Ogallala sediments largely intact. These preserved fan surfaces have poor surface water drainage, and thus retain ephemeral water for wetlands and groundwater recharge. Our findings suggest that the surface hydrology and associated ecosystems are transient features on million-year timescales, and reflect the mode of landscape evolution.}, } @article {pmid30232456, year = {2018}, author = {Reddy, G and Wong-Ng, J and Celani, A and Sejnowski, TJ and Vergassola, M}, title = {Glider soaring via reinforcement learning in the field.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {236-239}, doi = {10.1038/s41586-018-0533-0}, pmid = {30232456}, issn = {1476-4687}, support = {NCS-FO-1735004//National Science Foundation/International ; }, abstract = {Soaring birds often rely on ascending thermal plumes (thermals) in the atmosphere as they search for prey or migrate across large distances1-4. The landscape of convective currents is rugged and shifts on timescales of a few minutes as thermals constantly form, disintegrate or are transported away by the wind5,6. How soaring birds find and navigate thermals within this complex landscape is unknown. Reinforcement learning7 provides an appropriate framework in which to identify an effective navigational strategy as a sequence of decisions made in response to environmental cues. Here we use reinforcement learning to train a glider in the field to navigate atmospheric thermals autonomously. We equipped a glider of two-metre wingspan with a flight controller that precisely controlled the bank angle and pitch, modulating these at intervals with the aim of gaining as much lift as possible. A navigational strategy was determined solely from the glider's pooled experiences, collected over several days in the field. The strategy relies on on-board methods to accurately estimate the local vertical wind accelerations and the roll-wise torques on the glider, which serve as navigational cues. We establish the validity of our learned flight policy through field experiments, numerical simulations and estimates of the noise in measurements caused by atmospheric turbulence. Our results highlight the role of vertical wind accelerations and roll-wise torques as effective mechanosensory cues for soaring birds and provide a navigational strategy that is directly applicable to the development of autonomous soaring vehicles.}, } @article {pmid30232455, year = {2018}, author = {Gatsogiannis, C and Merino, F and Roderer, D and Balchin, D and Schubert, E and Kuhlee, A and Hayer-Hartl, M and Raunser, S}, title = {Tc toxin activation requires unfolding and refolding of a β-propeller.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {209-213}, doi = {10.1038/s41586-018-0556-6}, pmid = {30232455}, issn = {1476-4687}, abstract = {Tc toxins secrete toxic enzymes into host cells using a unique syringe-like injection mechanism. They are composed of three subunits, TcA, TcB and TcC. TcA forms the translocation channel and the TcB-TcC heterodimer functions as a cocoon that shields the toxic enzyme. Binding of the cocoon to the channel triggers opening of the cocoon and translocation of the toxic enzyme into the channel. Here we show in atomic detail how the assembly of the three components activates the toxin. We find that part of the cocoon completely unfolds and refolds into an alternative conformation upon binding. The presence of the toxic enzyme inside the cocoon is essential for its subnanomolar binding affinity for the TcA subunit. The enzyme passes through a narrow negatively charged constriction site inside the cocoon, probably acting as an extruder that releases the unfolded protein with its C terminus first into the translocation channel.}, } @article {pmid30232454, year = {2018}, author = {Athukoralage, JS and Rouillon, C and Graham, S and Grüschow, S and White, MF}, title = {Ring nucleases deactivate type III CRISPR ribonucleases by degrading cyclic oligoadenylate.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {277-280}, pmid = {30232454}, issn = {1476-4687}, abstract = {The CRISPR system provides adaptive immunity against mobile genetic elements in prokaryotes, using small CRISPR RNAs that direct effector complexes to degrade invading nucleic acids1-3. Type III effector complexes were recently demonstrated to synthesize a novel second messenger, cyclic oligoadenylate, on binding target RNA4,5. Cyclic oligoadenylate, in turn, binds to and activates ribonucleases and other factors-via a CRISPR-associated Rossman-fold domain-and thereby induces in the cell an antiviral state that is important for immunity. The mechanism of the 'off-switch' that resets the system is not understood. Here we identify the nuclease that degrades these cyclic oligoadenylate ring molecules. This 'ring nuclease' is itself a protein of the CRISPR-associated Rossman-fold family, and has a metal-independent mechanism that cleaves cyclic tetraadenylate rings to generate linear diadenylate species and switches off the antiviral state. The identification of ring nucleases adds an important insight to the CRISPR system.}, } @article {pmid30232453, year = {2018}, author = {Choe, J and Lin, S and Zhang, W and Liu, Q and Wang, L and Ramirez-Moya, J and Du, P and Kim, W and Tang, S and Sliz, P and Santisteban, P and George, RE and Richards, WG and Wong, KK and Locker, N and Slack, FJ and Gregory, RI}, title = {mRNA circularization by METTL3-eIF3h enhances translation and promotes oncogenesis.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {556-560}, pmid = {30232453}, issn = {1476-4687}, support = {P50 CA196530/CA/NCI NIH HHS/United States ; R01 CA197336/CA/NCI NIH HHS/United States ; R01 CA211328/CA/NCI NIH HHS/United States ; R01 GM086386/GM/NIGMS NIH HHS/United States ; }, abstract = {N6-methyladenosine (m6A) modification of mRNA is emerging as an important regulator of gene expression that affects different developmental and biological processes, and altered m6A homeostasis is linked to cancer1-5. m6A modification is catalysed by METTL3 and enriched in the 3' untranslated region of a large subset of mRNAs at sites close to the stop codon5. METTL3 can promote translation but the mechanism and relevance of this process remain unknown1. Here we show that METTL3 enhances translation only when tethered to reporter mRNA at sites close to the stop codon, supporting a mechanism of mRNA looping for ribosome recycling and translational control. Electron microscopy reveals the topology of individual polyribosomes with single METTL3 foci in close proximity to 5' cap-binding proteins. We identify a direct physical and functional interaction between METTL3 and the eukaryotic translation initiation factor 3 subunit h (eIF3h). METTL3 promotes translation of a large subset of oncogenic mRNAs-including bromodomain-containing protein 4-that is also m6A-modified in human primary lung tumours. The METTL3-eIF3h interaction is required for enhanced translation, formation of densely packed polyribosomes and oncogenic transformation. METTL3 depletion inhibits tumorigenicity and sensitizes lung cancer cells to BRD4 inhibition. These findings uncover a mechanism of translation control that is based on mRNA looping and identify METTL3-eIF3h as a potential therapeutic target for patients with cancer.}, } @article {pmid30232452, year = {2018}, author = {Anderegg, WRL and Konings, AG and Trugman, AT and Yu, K and Bowling, DR and Gabbitas, R and Karp, DS and Pacala, S and Sperry, JS and Sulman, BN and Zenes, N}, title = {Hydraulic diversity of forests regulates ecosystem resilience during drought.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {538-541}, doi = {10.1038/s41586-018-0539-7}, pmid = {30232452}, issn = {1476-4687}, support = {1714972//National Science Foundation/International ; 1802880//National Science Foundation/International ; }, abstract = {Plants influence the atmosphere through fluxes of carbon, water and energy1, and can intensify drought through land-atmosphere feedback effects2-4. The diversity of plant functional traits in forests, especially physiological traits related to water (hydraulic) transport, may have a critical role in land-atmosphere feedback, particularly during drought. Here we combine 352 site-years of eddy covariance measurements from 40 forest sites, remote-sensing observations of plant water content and plant functional-trait data to test whether the diversity in plant traits affects the response of the ecosystem to drought. We find evidence that higher hydraulic diversity buffers variation in ecosystem flux during dry periods across temperate and boreal forests. Hydraulic traits were the predominant significant predictors of cross-site patterns in drought response. By contrast, standard leaf and wood traits, such as specific leaf area and wood density, had little explanatory power. Our results demonstrate that diversity in the hydraulic traits of trees mediates ecosystem resilience to drought and is likely to have an important role in future ecosystem-atmosphere feedback effects in a changing climate.}, } @article {pmid30232451, year = {2018}, author = {Bussian, TJ and Aziz, A and Meyer, CF and Swenson, BL and van Deursen, JM and Baker, DJ}, title = {Clearance of senescent glial cells prevents tau-dependent pathology and cognitive decline.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {578-582}, pmid = {30232451}, issn = {1476-4687}, support = {R01 AG053229/AG/NIA NIH HHS/United States ; }, abstract = {Cellular senescence, which is characterized by an irreversible cell-cycle arrest1 accompanied by a distinctive secretory phenotype2, can be induced through various intracellular and extracellular factors. Senescent cells that express the cell cycle inhibitory protein p16INK4A have been found to actively drive naturally occurring age-related tissue deterioration3,4 and contribute to several diseases associated with ageing, including atherosclerosis5 and osteoarthritis6. Various markers of senescence have been observed in patients with neurodegenerative diseases7-9; however, a role for senescent cells in the aetiology of these pathologies is unknown. Here we show a causal link between the accumulation of senescent cells and cognition-associated neuronal loss. We found that the MAPTP301SPS19 mouse model of tau-dependent neurodegenerative disease10 accumulates p16INK4A-positive senescent astrocytes and microglia. Clearance of these cells as they arise using INK-ATTAC transgenic mice prevents gliosis, hyperphosphorylation of both soluble and insoluble tau leading to neurofibrillary tangle deposition, and degeneration of cortical and hippocampal neurons, thus preserving cognitive function. Pharmacological intervention with a first-generation senolytic modulates tau aggregation. Collectively, these results show that senescent cells have a role in the initiation and progression of tau-mediated disease, and suggest that targeting senescent cells may provide a therapeutic avenue for the treatment of these pathologies.}, } @article {pmid30232450, year = {2018}, author = {Liu, S and Kwon, M and Mannino, M and Yang, N and Renda, F and Khodjakov, A and Pellman, D}, title = {Nuclear envelope assembly defects link mitotic errors to chromothripsis.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {551-555}, doi = {10.1038/s41586-018-0534-z}, pmid = {30232450}, issn = {1476-4687}, support = {R01 GM059363/GM/NIGMS NIH HHS/United States ; R37 GM061345/GM/NIGMS NIH HHS/United States ; }, abstract = {Defects in the architecture or integrity of the nuclear envelope are associated with a variety of human diseases1. Micronuclei, one common nuclear aberration, are an origin for chromothripsis2, a catastrophic mutational process that is commonly observed in cancer3-5. Chromothripsis occurs after micronuclei spontaneously lose nuclear envelope integrity, which generates chromosome fragmentation6. Disruption of the nuclear envelope exposes DNA to the cytoplasm and initiates innate immune proinflammatory signalling7. Despite its importance, the basis of the fragility of the micronucleus nuclear envelope is not known. Here we show that micronuclei undergo defective nuclear envelope assembly. Only 'core' nuclear envelope proteins8,9 assemble efficiently on lagging chromosomes, whereas 'non-core' nuclear envelope proteins8,9, including nuclear pore complexes (NPCs), do not. Consequently, micronuclei fail to properly import key proteins that are necessary for the integrity of the nuclear envelope and genome. We show that spindle microtubules block assembly of NPCs and other non-core nuclear envelope proteins on lagging chromosomes, causing an irreversible defect in nuclear envelope assembly. Accordingly, experimental manipulations that position missegregated chromosomes away from the spindle correct defective nuclear envelope assembly, prevent spontaneous nuclear envelope disruption, and suppress DNA damage in micronuclei. Thus, during mitotic exit in metazoan cells, chromosome segregation and nuclear envelope assembly are only loosely coordinated by the timing of mitotic spindle disassembly. The absence of precise checkpoint controls may explain why errors during mitotic exit are frequent and often trigger catastrophic genome rearrangements4,5.}, } @article {pmid30232449, year = {2018}, author = {}, title = {Lab-death case, harassment rules and Luxembourg's new space agency.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {290-291}, doi = {10.1038/d41586-018-06693-7}, pmid = {30232449}, issn = {1476-4687}, } @article {pmid30232448, year = {2018}, author = {}, title = {Challenger states.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S20-S21}, doi = {10.1038/d41586-018-06623-7}, pmid = {30232448}, issn = {1476-4687}, } @article {pmid30232447, year = {2018}, author = {Conroy, G and Mallapaty, S and O'Meara, S and Padma, TV}, title = {Green shoots.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S30-S31}, doi = {10.1038/d41586-018-06626-4}, pmid = {30232447}, issn = {1476-4687}, } @article {pmid30232446, year = {2018}, author = {Krieger, A and Nogrady, B and Savage, N and Zastrow, M}, title = {Movers and shakers.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S26-S29}, doi = {10.1038/d41586-018-06625-5}, pmid = {30232446}, issn = {1476-4687}, } @article {pmid30232445, year = {2018}, author = {Langley, D and Theron, T}, title = {Discovery relies on strong support staff.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S24}, doi = {10.1038/d41586-018-06624-6}, pmid = {30232445}, issn = {1476-4687}, } @article {pmid30232444, year = {2018}, author = {Mallapaty, S}, title = {The fast track.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S9}, doi = {10.1038/d41586-018-06621-9}, pmid = {30232444}, issn = {1476-4687}, } @article {pmid30232443, year = {2018}, author = {Mallapaty, S}, title = {Predicting scientific success.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S32-S33}, doi = {10.1038/d41586-018-06627-3}, pmid = {30232443}, issn = {1476-4687}, } @article {pmid30232442, year = {2018}, author = {Armitage, C and Bourzac, K and Dolgin, E and Mallapaty, S}, title = {The world at their feet.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S10-S15}, doi = {10.1038/d41586-018-06622-8}, pmid = {30232442}, issn = {1476-4687}, } @article {pmid30232441, year = {2018}, author = {}, title = {A guide to the Nature Index.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {S37}, doi = {10.1038/d41586-018-06628-2}, pmid = {30232441}, issn = {1476-4687}, } @article {pmid30232440, year = {2018}, author = {Guglielmi, G}, title = {A new way to capture the brain's electrical symphony.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {300-302}, doi = {10.1038/d41586-018-06694-6}, pmid = {30232440}, issn = {1476-4687}, } @article {pmid30232439, year = {2018}, author = {}, title = {Austrian agency shows how to tackle scientific misconduct.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {285-286}, doi = {10.1038/d41586-018-06733-2}, pmid = {30232439}, issn = {1476-4687}, } @article {pmid30232438, year = {2018}, author = {}, title = {Filthy air is a global disgrace.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {285}, doi = {10.1038/d41586-018-06731-4}, pmid = {30232438}, issn = {1476-4687}, } @article {pmid30232437, year = {2018}, author = {Button, K}, title = {Reboot undergraduate courses for reproducibility.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {287}, doi = {10.1038/d41586-018-06692-8}, pmid = {30232437}, issn = {1476-4687}, } @article {pmid30232436, year = {2018}, author = {Cato, B}, title = {The 133rd Live Podcast of the Gourmando Resistance.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {426}, doi = {10.1038/d41586-018-06698-2}, pmid = {30232436}, issn = {1476-4687}, } @article {pmid30232435, year = {2018}, author = {de Groot, R and Sukhdev, P and Gough, M}, title = {Biodiversity: sparring makes us strong.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {309}, doi = {10.1038/d41586-018-06736-z}, pmid = {30232435}, issn = {1476-4687}, } @article {pmid30232434, year = {2018}, author = {Montana, J}, title = {Biodiversity: ideas need time to mature.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {309}, doi = {10.1038/d41586-018-06737-y}, pmid = {30232434}, issn = {1476-4687}, } @article {pmid30232433, year = {2018}, author = {Strassburg, BBN}, title = {Biodiversity: honour guidelines that reconcile world views.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {309}, doi = {10.1038/d41586-018-06734-1}, pmid = {30232433}, issn = {1476-4687}, } @article {pmid30232432, year = {2018}, author = {Watson, RT}, title = {Biodiversity: squabbles don't obscure the bigger picture.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {309}, doi = {10.1038/d41586-018-06735-0}, pmid = {30232432}, issn = {1476-4687}, } @article {pmid30232431, year = {2018}, author = {Lenzi, D and Lamb, WF and Hilaire, J and Kowarsch, M and Minx, JC}, title = {Don't deploy negative emissions technologies without ethical analysis.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {303-305}, doi = {10.1038/d41586-018-06695-5}, pmid = {30232431}, issn = {1476-4687}, } @article {pmid30232430, year = {2018}, author = {Fennel, T}, title = {Timing the action of light on matter.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {314-315}, doi = {10.1038/d41586-018-06687-5}, pmid = {30232430}, issn = {1476-4687}, } @article {pmid30232429, year = {2018}, author = {Tajima, T}, title = {Short proton bunches rapidly accelerate energetic electrons.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {318-319}, doi = {10.1038/d41586-018-06669-7}, pmid = {30232429}, issn = {1476-4687}, } @article {pmid30232428, year = {2018}, author = {Antoja, T and Helmi, A and Romero-Gómez, M and Katz, D and Babusiaux, C and Drimmel, R and Evans, DW and Figueras, F and Poggio, E and Reylé, C and Robin, AC and Seabroke, G and Soubiran, C}, title = {A dynamically young and perturbed Milky Way disk.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {360-362}, doi = {10.1038/s41586-018-0510-7}, pmid = {30232428}, issn = {1476-4687}, abstract = {The evolution of the Milky Way disk, which contains most of the stars in the Galaxy, is affected by several phenomena. For example, the bar and the spiral arms of the Milky Way induce radial migration of stars1 and can trap or scatter stars close to orbital resonances2. External perturbations from satellite galaxies can also have a role, causing dynamical heating of the Galaxy3, ring-like structures in the disk4 and correlations between different components of the stellar velocity5. These perturbations can also cause 'phase wrapping' signatures in the disk6-9, such as arched velocity structures in the motions of stars in the Galactic plane. Some manifestations of these dynamical processes have already been detected, including kinematic substructure in samples of nearby stars10-12, density asymmetries and velocities across the Galactic disk that differ from the axisymmetric and equilibrium expectations13, especially in the vertical direction11,14-16, and signatures of incomplete phase mixing in the disk7,12,17,18. Here we report an analysis of the motions of six million stars in the Milky Way disk. We show that the phase-space distribution contains different substructures with various morphologies, such as snail shells and ridges, when spatial and velocity coordinates are combined. We infer that the disk must have been perturbed between 300 million and 900 million years ago, consistent with estimates of the previous pericentric passage of the Sagittarius dwarf galaxy. Our findings show that the Galactic disk is dynamically young and that modelling it as time-independent and axisymmetric is incorrect.}, } @article {pmid30232427, year = {2018}, author = {Nagaoka, Y and Tan, R and Li, R and Zhu, H and Eggert, D and Wu, YA and Liu, Y and Wang, Z and Chen, O}, title = {Superstructures generated from truncated tetrahedral quantum dots.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {378-382}, doi = {10.1038/s41586-018-0512-5}, pmid = {30232427}, issn = {1476-4687}, support = {DMR-1332208//National Science Foundation/International ; DE-AC02-06CH11357//US Department of Energy/International ; }, abstract = {The assembly of uniform nanocrystal building blocks into well ordered superstructures is a fundamental strategy for the generation of meso- and macroscale metamaterials with emergent nanoscopic functionalities1-10. The packing of spherical nanocrystals, which frequently adopt dense, face-centred-cubic or hexagonal-close-packed arrangements at thermodynamic equilibrium, has been much more widely studied than that of non-spherical, polyhedral nanocrystals, despite the fact that the latter have intriguing anisotropic properties resulting from the shapes of the building blocks11-13. Here we report the packing of truncated tetrahedral quantum dot nanocrystals into three distinct superstructures-one-dimensional chiral tetrahelices, two-dimensional quasicrystal-approximant superlattices and three-dimensional cluster-based body-centred-cubic single supercrystals-by controlling the assembly conditions. Using techniques in real and reciprocal spaces, we successfully characterized the superstructures from their nanocrystal translational orderings down to the atomic-orientation alignments of individual quantum dots. Our packing models showed that formation of the nanocrystal superstructures is dominated by the selective facet-to-facet contact induced by the anisotropic patchiness of the tetrahedra. This study provides information about the packing of non-spherical nanocrystals into complex superstructures, and may enhance the potential of self-assembled nanocrystal metamaterials in practical applications.}, } @article {pmid30232426, year = {2018}, author = {Descours, B and Petitjean, G and Benkirane, M}, title = {Descours et al. reply.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {E29}, doi = {10.1038/s41586-018-0496-1}, pmid = {30232426}, issn = {1476-4687}, } @article {pmid30232425, year = {2018}, author = {Bertagnolli, LN and White, JA and Simonetti, FR and Beg, SA and Lai, J and Tomescu, C and Murray, AJ and Antar, AAR and Zhang, H and Margolick, JB and Hoh, R and Deeks, SG and Tebas, P and Montaner, LJ and Siliciano, RF and Laird, GM and Siliciano, JD}, title = {The role of CD32 during HIV-1 infection.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {E17-E19}, doi = {10.1038/s41586-018-0494-3}, pmid = {30232425}, issn = {1476-4687}, support = {P01 AI131306/AI/NIAID NIH HHS/United States ; R01 AI051178/AI/NIAID NIH HHS/United States ; R37 AI051178/AI/NIAID NIH HHS/United States ; UM1 AI126611/AI/NIAID NIH HHS/United States ; }, } @article {pmid30232424, year = {2018}, author = {Osuna, CE and Lim, SY and Kublin, JL and Apps, R and Chen, E and Mota, TM and Huang, SH and Ren, Y and Bachtel, ND and Tsibris, AM and Ackerman, ME and Jones, RB and Nixon, DF and Whitney, JB}, title = {Evidence that CD32a does not mark the HIV-1 latent reservoir.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {E20-E28}, doi = {10.1038/s41586-018-0495-2}, pmid = {30232424}, issn = {1476-4687}, } @article {pmid30232423, year = {2018}, author = {Pérez, L and Anderson, J and Chipman, J and Thorkelson, A and Chun, TW and Moir, S and Haase, AT and Douek, DC and Schacker, TW and Boritz, EA}, title = {Conflicting evidence for HIV enrichment in CD32+ CD4 T cells.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {E9-E16}, doi = {10.1038/s41586-018-0493-4}, pmid = {30232423}, issn = {1476-4687}, } @article {pmid30232422, year = {2018}, author = {Andronic, A and Braun-Munzinger, P and Redlich, K and Stachel, J}, title = {Decoding the phase structure of QCD via particle production at high energy.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {321-330}, doi = {10.1038/s41586-018-0491-6}, pmid = {30232422}, issn = {1476-4687}, abstract = {Recent studies based on lattice Monte Carlo simulations of quantum chromodynamics (QCD)-the theory of strong interactions-have demonstrated that at high temperature there is a phase change from confined hadronic matter to a deconfined quark-gluon plasma in which quarks and gluons can travel distances that greatly exceed the size of hadrons. Here we show that the phase structure of such strongly interacting matter can be decoded by analysing particle production in high-energy nuclear collisions within the framework of statistical hadronization, which accounts for the thermal distribution of particle species. Our results represent a phenomenological determination of the location of the phase boundary of strongly interacting matter, and imply quark-hadron duality at this boundary.}, } @article {pmid30232421, year = {2018}, author = {Ossiander, M and Riemensberger, J and Neppl, S and Mittermair, M and Schäffer, M and Duensing, A and Wagner, MS and Heider, R and Wurzer, M and Gerl, M and Schnitzenbaumer, M and Barth, JV and Libisch, F and Lemell, C and Burgdörfer, J and Feulner, P and Kienberger, R}, title = {Absolute timing of the photoelectric effect.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {374-377}, doi = {10.1038/s41586-018-0503-6}, pmid = {30232421}, issn = {1476-4687}, abstract = {Photoemission spectroscopy is central to understanding the inner workings of condensed matter, from simple metals and semiconductors to complex materials such as Mott insulators and superconductors1. Most state-of-the-art knowledge about such solids stems from spectroscopic investigations, and use of subfemtosecond light pulses can provide a time-domain perspective. For example, attosecond (10-18 seconds) metrology allows electron wave packet creation, transport and scattering to be followed on atomic length scales and on attosecond timescales2-7. However, previous studies could not disclose the duration of these processes, because the arrival time of the photons was not known with attosecond precision. Here we show that this main source of ambiguity can be overcome by introducing the atomic chronoscope method, which references all measured timings to the moment of light-pulse arrival and therefore provides absolute timing of the processes under scrutiny. Our proof-of-principle experiment reveals that photoemission from the tungsten conduction band can proceed faster than previously anticipated. By contrast, the duration of electron emanation from core states is correctly described by semiclassical modelling. These findings highlight the necessity of treating the origin, initial excitation and transport of electrons in advanced modelling of the attosecond response of solids, and our absolute data provide a benchmark. Starting from a robustly characterized surface, we then extend attosecond spectroscopy towards isolating the emission properties of atomic adsorbates on surfaces and demonstrate that these act as photoemitters with instantaneous response. We also find that the tungsten core-electron timing remains unchanged by the adsorption of less than one monolayer of dielectric atoms, providing a starting point for the exploration of excitation and charge migration in technologically and biologically relevant adsorbate systems.}, } @article {pmid30232420, year = {2018}, author = {Wilson, DJ and Bertram, RA and Needham, EF and van de Flierdt, T and Welsh, KJ and McKay, RM and Mazumder, A and Riesselman, CR and Jimenez-Espejo, FJ and Escutia, C}, title = {Ice loss from the East Antarctic Ice Sheet during late Pleistocene interglacials.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {383-386}, doi = {10.1038/s41586-018-0501-8}, pmid = {30232420}, issn = {1476-4687}, abstract = {Understanding ice sheet behaviour in the geological past is essential for evaluating the role of the cryosphere in the climate system and for projecting rates and magnitudes of sea level rise in future warming scenarios1-4. Although both geological data5-7 and ice sheet models3,8 indicate that marine-based sectors of the East Antarctic Ice Sheet were unstable during Pliocene warm intervals, the ice sheet dynamics during late Pleistocene interglacial intervals are highly uncertain3,9,10. Here we provide evidence from marine sedimentological and geochemical records for ice margin retreat or thinning in the vicinity of the Wilkes Subglacial Basin of East Antarctica during warm late Pleistocene interglacial intervals. The most extreme changes in sediment provenance, recording changes in the locus of glacial erosion, occurred during marine isotope stages 5, 9, and 11, when Antarctic air temperatures11 were at least two degrees Celsius warmer than pre-industrial temperatures for 2,500 years or more. Hence, our study indicates a close link between extended Antarctic warmth and ice loss from the Wilkes Subglacial Basin, providing ice-proximal data to support a contribution to sea level from a reduced East Antarctic Ice Sheet during warm interglacial intervals. While the behaviour of other regions of the East Antarctic Ice Sheet remains to be assessed, it appears that modest future warming may be sufficient to cause ice loss from the Wilkes Subglacial Basin.}, } @article {pmid30232369, year = {2018}, author = {Goerner-Potvin, P and Bourque, G}, title = {Computational tools to unmask transposable elements.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {688-704}, doi = {10.1038/s41576-018-0050-x}, pmid = {30232369}, issn = {1471-0064}, abstract = {A substantial proportion of the genome of many species is derived from transposable elements (TEs). Moreover, through various self-copying mechanisms, TEs continue to proliferate in the genomes of most species. TEs have contributed numerous regulatory, transcript and protein innovations and have also been linked to disease. However, notwithstanding their demonstrated impact, many genomic studies still exclude them because their repetitive nature results in various analytical complexities. Fortunately, a growing array of methods and software tools are being developed to cater for them. This Review presents a summary of computational resources for TEs and highlights some of the challenges and remaining gaps to perform comprehensive genomic analyses that do not simply 'mask' repeats.}, } @article {pmid30232266, year = {2018}, author = {Yang, D and Kim, WJ and Yoo, SM and Choi, JH and Ha, SH and Lee, MH and Lee, SY}, title = {Repurposing type III polyketide synthase as a malonyl-CoA biosensor for metabolic engineering in bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9835-9844}, pmid = {30232266}, issn = {1091-6490}, mesh = {*Bacterial Proteins/genetics/metabolism ; Biosensing Techniques/*methods ; *Corynebacterium glutamicum/enzymology/genetics ; *Escherichia coli/enzymology/genetics ; Malonyl Coenzyme A/*analysis ; *Metabolic Engineering ; *Polyketide Synthases/genetics/metabolism ; *Pseudomonas putida/enzymology/genetics ; }, abstract = {Malonyl-CoA is an important central metabolite for the production of diverse valuable chemicals including natural products, but its intracellular availability is often limited due to the competition with essential cellular metabolism. Several malonyl-CoA biosensors have been developed for high-throughput screening of targets increasing the malonyl-CoA pool. However, they are limited for use only in Escherichia coli and Saccharomyces cerevisiae and require multiple signal transduction steps. Here we report development of a colorimetric malonyl-CoA biosensor applicable in three industrially important bacteria: E. coli, Pseudomonas putida, and Corynebacterium glutamicum RppA, a type III polyketide synthase producing red-colored flaviolin, was repurposed as a malonyl-CoA biosensor in E. coli Strains with enhanced malonyl-CoA accumulation were identifiable by the colorimetric screening of cells showing increased red color. Other type III polyketide synthases could also be repurposed as malonyl-CoA biosensors. For target screening, a 1,858 synthetic small regulatory RNA library was constructed and applied to find 14 knockdown gene targets that generally enhanced malonyl-CoA level in E. coli These knockdown targets were applied to produce two polyketide (6-methylsalicylic acid and aloesone) and two phenylpropanoid (resveratrol and naringenin) compounds. Knocking down these genes alone or in combination, and also in multiple different E. coli strains for two polyketide cases, allowed rapid development of engineered strains capable of enhanced production of 6-methylsalicylic acid, aloesone, resveratrol, and naringenin to 440.3, 30.9, 51.8, and 103.8 mg/L, respectively. The malonyl-CoA biosensor developed here is a simple tool generally applicable to metabolic engineering of microorganisms to achieve enhanced production of malonyl-CoA-derived chemicals.}, } @article {pmid30232265, year = {2018}, author = {Hollenbeck, EC and Antonoplis, A and Chai, C and Thongsomboon, W and Fuller, GG and Cegelski, L}, title = {Phosphoethanolamine cellulose enhances curli-mediated adhesion of uropathogenic Escherichia coli to bladder epithelial cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10106-10111}, pmid = {30232265}, issn = {1091-6490}, mesh = {Bacterial Adhesion/*drug effects ; Bacterial Proteins/genetics/*metabolism ; Cell Line ; Cellulose/*adverse effects/pharmacology ; Epithelial Cells/*metabolism/microbiology/ultrastructure ; Ethanolamines/*adverse effects/pharmacology ; Humans ; Urinary Bladder/*metabolism/microbiology/ultrastructure ; Uropathogenic Escherichia coli/*metabolism/pathogenicity/ultrastructure ; Urothelium/*metabolism/microbiology/ultrastructure ; }, abstract = {Uropathogenic Escherichia coli (UPEC) are the major causative agents of urinary tract infections, employing numerous molecular strategies to contribute to adhesion, colonization, and persistence in the bladder niche. Identifying strategies to prevent adhesion and colonization is a promising approach to inhibit bacterial pathogenesis and to help preserve the efficacy of available antibiotics. This approach requires an improved understanding of the molecular determinants of adhesion to the bladder urothelium. We designed experiments using a custom-built live cell monolayer rheometer (LCMR) to quantitatively measure individual and combined contributions of bacterial cell surface structures [type 1 pili, curli, and phosphoethanolamine (pEtN) cellulose] to bladder cell adhesion. Using the UPEC strain UTI89, isogenic mutants, and controlled conditions for the differential production of cell surface structures, we discovered that curli can promote stronger adhesive interactions with bladder cells than type 1 pili. Moreover, the coproduction of curli and pEtN cellulose enhanced adhesion. The LCMR enables the evaluation of adhesion under high-shear conditions to reveal this role for pEtN cellulose which escaped detection using conventional tissue culture adhesion assays. Together with complementary biochemical experiments, the results support a model wherein cellulose serves a mortar-like function to promote curli association with and around the bacterial cell surface, resulting in increased bacterial adhesion strength at the bladder cell surface.}, } @article {pmid30232264, year = {2018}, author = {Green, JP and Yu, S and Martín-Sánchez, F and Pelegrin, P and Lopez-Castejon, G and Lawrence, CB and Brough, D}, title = {Chloride regulates dynamic NLRP3-dependent ASC oligomerization and inflammasome priming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9371-E9380}, pmid = {30232264}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MR/N029992/1//Medical Research Council/United Kingdom ; 104192/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; CARD Signaling Adaptor Proteins/genetics/*metabolism ; Chlorides/*metabolism ; Female ; Inflammasomes/genetics/*metabolism ; Inflammation/genetics/metabolism/pathology ; Interleukin-1beta/genetics/metabolism ; Ion Transport/genetics ; Male ; Mice ; Mice, Knockout ; NIMA-Related Kinases/genetics/metabolism ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism ; Potassium/metabolism ; *Protein Multimerization ; }, abstract = {The NLRP3 inflammasome is an important regulator of inflammation and immunity. It is a multimolecular platform formed within cells that facilitates the activation of proinflammatory caspases to drive secretion of cytokines such as interleukin-1β (IL-1β). Knowledge of the mechanisms regulating formation of the NLRP3 inflammasome is incomplete. Here we report Cl- channel-dependent formation of dynamic ASC oligomers and inflammasome specks that remain inactive in the absence of K+ efflux. Formed after Cl- efflux exclusively, ASC specks are NLRP3 dependent, reversible, and inactive, although they further prime inflammatory responses, accelerating and enhancing release of IL-1β in response to a K+ efflux-inducing stimulus. NEK7 is a specific K+ sensor and does not associate with NLRP3 under conditions stimulating exclusively Cl- efflux, but does after K+ efflux, activating the complex driving inflammation. Our investigation delivers mechanistic understanding into inflammasome activation and the regulation of inflammatory responses.}, } @article {pmid30232263, year = {2018}, author = {Sayed, FA and Telpoukhovskaia, M and Kodama, L and Li, Y and Zhou, Y and Le, D and Hauduc, A and Ludwig, C and Gao, F and Clelland, C and Zhan, L and Cooper, YA and Davalos, D and Akassoglou, K and Coppola, G and Gan, L}, title = {Differential effects of partial and complete loss of TREM2 on microglial injury response and tauopathy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10172-10177}, pmid = {30232263}, issn = {1091-6490}, support = {T32 GM007618/GM/NIGMS NIH HHS/United States ; R35 NS097976/NS/NINDS NIH HHS/United States ; P30 NS062691/NS/NINDS NIH HHS/United States ; R01 AG051390/AG/NIA NIH HHS/United States ; R01 AG054214/AG/NIA NIH HHS/United States ; F31 AG058505/AG/NIA NIH HHS/United States ; }, mesh = {Aging/genetics/metabolism/pathology ; *Alzheimer Disease/genetics/metabolism/pathology ; Animals ; *Haploinsufficiency ; *Hemizygote ; *Membrane Glycoproteins/genetics/metabolism ; Mice ; Mice, Knockout ; Microglia/*metabolism/pathology ; *Mutation, Missense ; *Receptors, Immunologic/genetics/metabolism ; }, abstract = {Alzheimer's disease (AD), the most common form of dementia, is characterized by the abnormal accumulation of amyloid plaques and hyperphosphorylated tau aggregates, as well as microgliosis. Hemizygous missense variants in Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) are associated with elevated risk for developing late-onset AD. These variants are hypothesized to result in loss of function, mimicking TREM2 haploinsufficiency. However, the consequences of TREM2 haploinsufficiency on tau pathology and microglial function remain unknown. We report the effects of partial and complete loss of TREM2 on microglial function and tau-associated deficits. In vivo imaging revealed that microglia from aged TREM2-haploinsufficient mice show a greater impairment in their injury response compared with microglia from aged TREM2-KO mice. In transgenic mice expressing mutant human tau, TREM2 haploinsufficiency, but not complete loss of TREM2, increased tau pathology. In addition, whereas complete TREM2 deficiency protected against tau-mediated microglial activation and atrophy, TREM2 haploinsufficiency elevated expression of proinflammatory markers and exacerbated atrophy at a late stage of disease. The differential effects of partial and complete loss of TREM2 on microglial function and tau pathology provide important insights into the critical role of TREM2 in AD pathogenesis.}, } @article {pmid30232262, year = {2018}, author = {Klasse, PJ}, title = {Collusion between neutralizing antibodies and other immune factions in the destruction of adenoviral vectors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10201-10203}, pmid = {30232262}, issn = {1091-6490}, mesh = {Adenoviridae/genetics ; *Antibodies, Neutralizing ; Antibodies, Viral ; Genetic Therapy ; *Genetic Vectors ; }, } @article {pmid30232261, year = {2018}, author = {Taracanova, A and Tsilioni, I and Conti, P and Norwitz, ER and Leeman, SE and Theoharides, TC}, title = {Substance P and IL-33 administered together stimulate a marked secretion of IL-1β from human mast cells, inhibited by methoxyluteolin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9381-E9390}, pmid = {30232261}, issn = {1091-6490}, mesh = {Biphenyl Compounds/pharmacology ; Caspase 1/metabolism ; Cell Line, Tumor ; Humans ; Interleukin-1beta/*metabolism ; Interleukin-33/*pharmacology ; Luteolin/*pharmacology ; Mast Cells/cytology/*metabolism ; Piperidines/pharmacology ; Substance P/*pharmacology ; }, abstract = {Mast cells are critical for allergic and inflammatory responses in which the peptide substance P (SP) and the cytokine IL-33 are involved. SP (0.01-1 μM) administered together with IL-33 (30 ng/mL) to human cultured LAD2 mast cells stimulates a marked increase (P < 0.0001) in secretion of the proinflammatory cytokine IL-1β. Preincubation of LAD2 (30 min) with the SP receptor (NK-1) antagonists L-733,060 (10 μM) or CP-96345 (10 µM) inhibits (P < 0.001) secretion of IL-1β stimulated by either SP (1 μM) or SP together with IL-33 (30 ng/mL). Surprisingly, secretion of IL-1β stimulated by IL-33 is inhibited (P < 0.001) by each NK-1 antagonist. Preincubation with an antibody against the IL-33 receptor ST2 inhibits (P < 0.0001) secretion of IL-1β stimulated either by IL-33 or together with SP. The combination of SP (1 μM) with IL-33 (30 ng/mL) increases IL-1β gene expression by 90-fold in LAD2 cells and by 200-fold in primary cultured mast cells from human umbilical cord blood. The combination of SP and IL-33 increases intracellular levels of IL-1β in LAD2 by 100-fold and gene expression of IL-1β and procaspase-1 by fivefold and pro-IL-1β by twofold. Active caspase-1 is present even in unstimulated cells and is detected extracellularly. Preincubation of LAD2 cells with the natural flavonoid methoxyluteolin (1-100 mM) inhibits (P < 0.0001) secretion and gene expression of IL-1β, procaspase-1, and pro-IL-1β. Mast cell secretion of IL-1β in response to SP and IL-33 reveals targets for the development of antiinflammatory therapies.}, } @article {pmid30232260, year = {2018}, author = {Yang, K and Stanfield, RL and Martinez-Yamout, MA and Dyson, HJ and Wilson, IA and Wright, PE}, title = {Structural basis for cooperative regulation of KIX-mediated transcription pathways by the HTLV-1 HBZ activation domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10040-10045}, pmid = {30232260}, issn = {1091-6490}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; R01 CA214054/CA/NCI NIH HHS/United States ; }, mesh = {Basic-Leucine Zipper Transcription Factors/*chemistry/metabolism ; Human T-lymphotropic virus 1/*chemistry/metabolism ; Humans ; Protein Domains ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Proto-Oncogene Proteins c-myb/*chemistry/metabolism ; Retroviridae Proteins/*chemistry/metabolism ; *Transcription, Genetic ; }, abstract = {The human T cell leukemia virus I basic leucine zipper protein (HTLV-1 HBZ) maintains chronic viral infection and promotes leukemogenesis through poorly understood mechanisms involving interactions with the KIX domain of the transcriptional coactivator CBP and its paralog p300. The KIX domain binds regulatory proteins at the distinct MLL and c-Myb/pKID sites to form binary or ternary complexes. The intrinsically disordered N-terminal activation domain of HBZ (HBZ AD) deregulates cellular signaling pathways by competing directly with cellular and viral transcription factors for binding to the MLL site and by allosterically perturbing binding of the transactivation domain of the hematopoietic transcription factor c-Myb. Crystal structures of the ternary KIX:c-Myb:HBZ complex show that the HBZ AD recruits two KIX:c-Myb entities through tandem amphipathic motifs (L/V)(V/L)DGLL and folds into a long α-helix upon binding. Isothermal titration calorimetry reveals strong cooperativity in binding of the c-Myb activation domain to the KIX:HBZ complex and in binding of HBZ to the KIX:c-Myb complex. In addition, binding of KIX to the two HBZ (V/L)DGLL motifs is cooperative; the structures suggest that this cooperativity is achieved through propagation of the HBZ α-helix beyond the first binding motif. Our study suggests that the unique structural flexibility and the multiple interaction motifs of the intrinsically disordered HBZ AD are responsible for its potency in hijacking KIX-mediated transcription pathways. The KIX:c-Myb:HBZ complex provides an example of cooperative stabilization in a transcription factor:coactivator network and gives insights into potential mechanisms through which HBZ dysregulates hematopoietic transcriptional programs and promotes T cell proliferation.}, } @article {pmid30232259, year = {2018}, author = {Vazey, EM and Moorman, DE and Aston-Jones, G}, title = {Phasic locus coeruleus activity regulates cortical encoding of salience information.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9439-E9448}, pmid = {30232259}, issn = {1091-6490}, support = {K99 MH104716/MH/NIMH NIH HHS/United States ; R00 MH104716/MH/NIMH NIH HHS/United States ; R01 MH092868/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Evoked Potentials/*physiology ; Locus Coeruleus/cytology/*physiology ; Male ; Neurons/cytology/*metabolism ; Optogenetics ; Rats ; Rats, Long-Evans ; }, abstract = {Phasic activation of locus coeruleus (LC)-norepinephrine (NE) neurons is associated with focused attention and behavioral responses to salient stimuli. We used cell-type-specific optogenetics and single-unit neurophysiology to identify how LC activity influences neural encoding of sensory information. We found that phasic, but not tonic, LC-NE photoactivation generated a distinct event-related potential (ERP) across cortical regions. Salient sensory stimuli (which innately trigger phasic LC activity) produced strong excitatory cortical responses during this ERP window. Application of weaker, nonsalient stimuli produced limited responses, but these responses were elevated to salient stimulus levels when they were temporally locked with phasic LC photoactivation. These results demonstrate that phasic LC activity enhances cortical encoding of salient stimuli by facilitating long-latency signals within target regions in response to stimulus intensity/salience. The LC-driven salience signal identified here provides a measure of phasic LC activity that can be used to investigate the LC's role in attentional processing across species.}, } @article {pmid30232258, year = {2018}, author = {Streltsov, SV and Roizen, VV and Ushakov, AV and Oganov, AR and Khomskii, DI}, title = {Old puzzle of incommensurate crystal structure of calaverite AuTe2 and predicted stability of novel AuTe compound.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9945-9950}, pmid = {30232258}, issn = {1091-6490}, abstract = {Gold is a very inert element, which forms relatively few compounds. Among them is a unique material-mineral calaverite, [Formula: see text] Besides being the only compound in nature from which one can extract gold on an industrial scale, it is a rare example of a natural mineral with incommensurate crystal structure. Moreover, it is one of few systems based on Au, which become superconducting (at elevated pressure or doped by Pd and Pt). Using ab initio calculations we theoretically explain these unusual phenomena in the picture of negative charge-transfer energy and self-doping, with holes being largely in the Te [Formula: see text] bands. This scenario naturally explains incommensurate crystal structure of [Formula: see text], and it also suggests a possible mechanism of superconductivity. An ab initio evolutionary search for stable compounds in the Au-Te system confirms stability of [Formula: see text] and [Formula: see text] and leads to a prediction of an as yet unknown stable compound AuTe, which until now has not been synthesized.}, } @article {pmid30232257, year = {2018}, author = {Leonavicius, K and Royer, C and Preece, C and Davies, B and Biggins, JS and Srinivas, S}, title = {Mechanics of mouse blastocyst hatching revealed by a hydrogel-based microdeformation assay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10375-10380}, pmid = {30232257}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; BB/J014427/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 203141/Z/16/Z//Wellcome Trust/United Kingdom ; 103788/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Blastocyst/cytology/*physiology ; Cells, Cultured ; Cryopreservation ; Embryo Transfer ; Embryo, Mammalian/cytology/*physiology ; Embryonic Development/*physiology ; Female ; *Fertilization in Vitro ; Hydrogels/*chemistry ; Mice ; Pregnancy ; Zona Pellucida/*physiology ; }, abstract = {Mammalian embryos are surrounded by an acellular shell, the zona pellucida. Hatching out of the zona is crucial for implantation and continued development of the embryo. Clinically, problems in hatching can contribute to failure in assisted reproductive intervention. Although hatching is fundamentally a mechanical process, due to limitations in methodology most studies focus on its biochemical properties. To understand the role of mechanical forces in hatching, we developed a hydrogel deformation-based method and analytical approach for measuring pressure in cyst-like tissues. Using this approach, we found that, in cultured blastocysts, pressure increased linearly, with intermittent falls. Inhibition of Na/K-ATPase led to a dosage-dependent reduction in blastocyst cavity pressure, consistent with its requirement for cavity formation. Reducing blastocyst pressure reduced the probability of hatching, highlighting the importance of mechanical forces in hatching. These measurements allowed us to infer details of microphysiology such as osmolarity, ion and water transport kinetics across the trophectoderm, and zona stiffness, allowing us to model the embryo as a thin-shell pressure vessel. We applied this technique to test whether cryopreservation, a process commonly used in assisted reproductive technology (ART), leads to alteration of the embryo and found that thawed embryos generated significantly lower pressure than fresh embryos, a previously unknown effect of cryopreservation. We show that reduced pressure is linked to delayed hatching. Our approach can be used to optimize in vitro fertilization (IVF) using precise measurement of embryo microphysiology. It is also applicable to other biological systems involving cavity formation, providing an approach for measuring forces in diverse contexts.}, } @article {pmid30232256, year = {2018}, author = {Feng, S and Cheng, X and Zhang, L and Lu, X and Chaudhary, S and Teng, R and Frederickson, C and Champion, MM and Zhao, R and Cheng, L and Gong, Y and Deng, H and Lu, X}, title = {Myeloid-derived suppressor cells inhibit T cell activation through nitrating LCK in mouse cancers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10094-10099}, pmid = {30232256}, issn = {1091-6490}, support = {KL2 TR002530/TR/NCATS NIH HHS/United States ; UL1 TR002529/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Lewis Lung/genetics/*immunology/pathology ; Humans ; Jurkat Cells ; *Lymphocyte Activation ; Lymphocyte Specific Protein Tyrosine Kinase p56(lck)/genetics/*immunology ; Male ; Mice ; Myeloid-Derived Suppressor Cells/*immunology/pathology ; Prostatic Neoplasms, Castration-Resistant/genetics/*immunology/pathology ; Receptors, Antigen, T-Cell/genetics/*immunology ; T-Lymphocytes/*immunology/pathology ; }, abstract = {Potent immunosuppressive mechanisms within the tumor microenvironment contribute to the resistance of aggressive human cancers to immune checkpoint blockade (ICB) therapy. One of the main mechanisms for myeloid-derived suppressor cells (MDSCs) to induce T cell tolerance is through secretion of reactive nitrogen species (RNS), which nitrates tyrosine residues in proteins involved in T cell function. However, so far very few nitrated proteins have been identified. Here, using a transgenic mouse model of prostate cancer and a syngeneic cell line model of lung cancer, we applied a nitroproteomic approach based on chemical derivation of 3-nitrotyrosine and identified that lymphocyte-specific protein tyrosine kinase (LCK), an initiating tyrosine kinase in the T cell receptor signaling cascade, is nitrated at Tyr394 by MDSCs. LCK nitration inhibits T cell activation, leading to reduced interleukin 2 (IL2) production and proliferation. In human T cells with defective endogenous LCK, wild type, but not nitrated LCK, rescues IL2 production. In the mouse model of castration-resistant prostate cancer (CRPC) by prostate-specific deletion of Pten, p53, and Smad4, CRPC is resistant to an ICB therapy composed of antiprogrammed cell death 1 (PD1) and anticytotoxic-T lymphocyte-associated protein 4 (CTLA4) antibodies. However, we showed that ICB elicits strong anti-CRPC efficacy when combined with an RNS neutralizing agent. Together, these data identify a previously unknown mechanism of T cell inactivation by MDSC-induced protein nitration and illuminate a clinical path hypothesis for combining ICB with RNS-reducing agents in the treatment of CRPC.}, } @article {pmid30231959, year = {2018}, author = {Li, D and Jiang, H and Han, L and Li, Y and Zhao, J and Jiang, S and Wang, X and Xiang, W}, title = {Lentzea terrae sp. nov., isolated from soil and an emended description of Lentzea soli.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3528-3533}, doi = {10.1099/ijsem.0.003024}, pmid = {30231959}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinobacterium, designated strain NEAU-LZS 42T, was isolated from soil collected from Mount Song, Henan Province, China, and characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the organism should be assigned to the genus Lentzea and had the closest relationship with Lentzea soli NEAU-LZC 7T (99.1 % similarity) and Lentzea cavernae SYSU K10001T (98.2 %). The major menaquinones were identified as MK-9(H4) and MK-9(H2). The phospholipid profile was found to contain diphosphatidylglycerol, phosphatidylethanolamine, hydroxy-phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, glycophospholipid and three unidentified lipids. The major fatty acids were iso-C16 : 0, C16 : 1ω7c and C16 : 0. DNA-DNA hybridization results and some phenotypic characteristics indicated that strain NEAU-LZS 42T could be clearly differentiated from L. soli NEAU-LZC 7T and L. cavernae SYSU K10001T. Therefore, it is concluded that strain NEAU-LZS 42T represents a novel species of the genus Lentzea, for which the name Lentzea terrae sp. nov. is proposed. The type stain is NEAU-LZS 42T (=CGMCC 4.7428T=DSM 105696T).}, } @article {pmid30231958, year = {2018}, author = {Xu, S and Wang, D and Wei, Y and Cui, Q and Li, W}, title = {Marinobacter bohaiensis sp. nov., a moderate halophile isolated from benthic sediment of the Bohai Sea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3534-3539}, doi = {10.1099/ijsem.0.003025}, pmid = {30231958}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Marinobacter/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, motile, aerobic and rod-shaped bacterial strain, designated T17T, was isolated from benthic sediment sampled at Jiaozhou Bay, Bohai Sea, China, and its taxonomic position was investigated. The 16S rRNA gene sequence of strain T17T exhibited the highest similarity values to those of the type strain Marinobacter lacisalsi FP2.5 (96.2 %) and Marinobacter koreensis DD-M3T (96.2 %). Strain T17T grew optimally at 35 °C, pH 7.0-8.0 and in the presence of 6.0-10.0 % (w/v) NaCl. The predominant ubiquinone in strain T17T was identified as Q-9. The major fatty acids of strain T17T were C12 : 0, C16 : 0 and C16 : 0 10-CH3. The major polar lipids of strain T17T were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidglycerol, an unidentified aminolipid and an unidentified phospholipid. The DNA G+C content of strain T17T was 63.0 mol%. The draft genome sequence of strain T17T includes 4 755 891 bp in total (N50=2 856 325 bp) with a medium read coverage of 100.0x and 11 scaffolds. In silico DNA-DNA hybridization with the three type strains showed 20.3, 19.7 and 19.9 % relatedness to Marinobacter santoriniensis NKSG1T, Marinobacter segnicrescens SS11B1-4T and Marinobacter daqiaonensis CGMCC 1.9167T, respectively. On the basis of the phenotypic, phylogenetic, genomic and chemotaxonomic properties, strain T17T is considered to represent a novel species within the genus Marinobacter, for which the name Marinobacterbohaiensis sp. nov. is proposed. The type strain is T17T (=KCTC 52710T=MCCC 1K03282T).}, } @article {pmid30231957, year = {2018}, author = {Shi, MJ and Wang, C and Liu, ZY and Jiang, LX and Du, ZJ}, title = {Reichenbachiella versicolor sp. nov., isolated from red alga.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3523-3527}, doi = {10.1099/ijsem.0.003023}, pmid = {30231957}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodophyta/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, strictly aerobic, non-flagellated, rod-shaped bacterial strain, designated DC003T, was isolated from the alga Gracilariablodgettii of the phylum Rhodophyta collected from the coast of Lingshui county, Hainan, China. The strain grew optimally at 28 °C, pH 7.0-7.5 and in the presence of 2.0-3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed strain DC003T to be within the genus Reichenbachiella, and most closely related to Reichenbachiella agariperforans JCM11238 (94.5 %), followed by Reichenbachiella faecimaris JCM 16588T (94.2 %). The major respiratory quinone was menaquinone 7 and the major fatty acids were iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH). The polar lipids consisted of phosphatidylethanolamine, two unidentified aminophospholipids, three unidentified phospholipids and 10 unidentified lipids. The G+C content of the genomic DNA was 37.1 mol%. On the basis of the phenotypic, genotypic and phylogenetic analysis, strain DC003T is considered to represent a novel species of the genus Reichenbachiella, for which the name Reichenbachiellaversicolor sp. nov. is proposed. The type strain is DC003T (=KCTC 42867T=MCCC 1H00130T).}, } @article {pmid30231956, year = {2018}, author = {van Ingen, J and Turenne, CY and Tortoli, E and Wallace, RJ and Brown-Elliott, BA}, title = {A definition of the Mycobacterium avium complex for taxonomical and clinical purposes, a review.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3666-3677}, doi = {10.1099/ijsem.0.003026}, pmid = {30231956}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Mycobacterium avium Complex/*classification ; Nontuberculous Mycobacteria/*classification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Nontuberculous mycobacteria, particularly the Mycobacterium avium complex (MAC) bacteria, are increasingly recognized as opportunistic pathogens of humans. As a result, studies on antibiotic treatment and taxonomy of the MAC are intensifying, but an updated definition of what constitutes the MAC, either for taxonomical studies or for clinical purposes, is lacking. On the basis of literature review and phylogenetic analyses, we propose to define the MAC as a grouping of slow-growing mycobacteria that show corresponding values in at least two of the following targets against either M. avium ATCC 25291T or Mycobacterium intracellulare ATCC 13950T: >99.4 % sequence identity for the full 16S rRNA gene, >98.7 % for the partial (5') 16S rRNA gene, >97.3 % for hsp65 and >94.4 % for rpoB region V. A >97.5 % value in concatenated analyses of >2500 bp that includes 16S rRNA, hsp65 and rpoB gene sequence data or ≥85 % average nucleotide identity to M. avium ATCC 25291T or M. intracellulare ATCC 13950T on basis of whole genome sequencing data is recommended. This molecular definition is based on the distances observed between the classical members of the MAC, M. avium and M. intracellulare. Applying this definition, the complex currently consists of 12 validly published species: Mycobacterium avium, Mycobacterium intracellulare, Mycobacterium chimaera, Mycobacterium colombiense, Mycobacterium arosiense, Mycobacterium vulneris, Mycobacterium bouchedurhonense, Mycobacterium timonense, Mycobacterium marseillense, Mycobacterium yongonense, Mycobacterium paraintracellulare and Mycobacterium lepraemurium.}, } @article {pmid30231937, year = {2018}, author = {Michel, AJ and Ward, LM and Goffredi, SK and Dawson, KS and Baldassarre, DT and Brenner, A and Gotanda, KM and McCormack, JE and Mullin, SW and O'Neill, A and Tender, GS and Uy, JAC and Yu, K and Orphan, VJ and Chaves, JA}, title = {The gut of the finch: uniqueness of the gut microbiome of the Galápagos vampire finch.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {167}, pmid = {30231937}, issn = {2049-2618}, abstract = {BACKGROUND: Darwin's finches are a clade of 19 species of passerine birds native to the Galápagos Islands, whose biogeography, specialized beak morphologies, and dietary choices-ranging from seeds to blood-make them a classic example of adaptive radiation. While these iconic birds have been intensely studied, the composition of their gut microbiome and the factors influencing it, including host species, diet, and biogeography, has not yet been explored.

RESULTS: We characterized the microbial community associated with 12 species of Darwin's finches using high-throughput 16S rRNA sequencing of fecal samples from 114 individuals across nine islands, including the unusual blood-feeding vampire finch (Geospiza septentrionalis) from Darwin and Wolf Islands. The phylum-level core gut microbiome for Darwin's finches included the Firmicutes, Gammaproteobacteria, and Actinobacteria, with members of the Bacteroidetes at conspicuously low abundance. The gut microbiome was surprisingly well conserved across the diversity of finch species, with one exception-the vampire finch-which harbored bacteria that were either absent or extremely rare in other finches, including Fusobacterium, Cetobacterium, Ureaplasma, Mucispirillum, Campylobacter, and various members of the Clostridia-bacteria known from the guts of carnivorous birds and reptiles. Complementary stable isotope analysis of feathers revealed exceptionally high δ15N isotope values in the vampire finch, resembling top marine predators. The Galápagos archipelago is also known for extreme wet and dry seasons, and we observed a significant seasonal shift in the gut microbial community of five additional finch species sampled during both seasons.

CONCLUSIONS: This study demonstrates the overall conservatism of the finch gut microbiome over short (< 1 Ma) divergence timescales, except in the most extreme case of dietary specialization, and elevates the evolutionary importance of seasonal shifts in driving not only species adaptation, but also gut microbiome composition.}, } @article {pmid30231936, year = {2018}, author = {Al-Breiki, RD and Kjeldsen, SR and Afzal, H and Al Hinai, MS and Zenger, KR and Jerry, DR and Al-Abri, MA and Delghandi, M}, title = {Genome-wide SNP analyses reveal high gene flow and signatures of local adaptation among the scalloped spiny lobster (Panulirus homarus) along the Omani coastline.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {690}, pmid = {30231936}, issn = {1471-2164}, support = {ORG/SQU/EBR/13/027//The Research Council of Oman (TRC)/ ; }, mesh = {*Adaptation, Physiological ; Animals ; *Gene Flow ; *Genetic Markers ; Genetics, Population ; *Genome ; Palinuridae/*genetics ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: The scalloped spiny lobster (Panulirus homarus) is a popular seafood commodity worldwide and an important export item from Oman. Annual catches in commercial fisheries are in serious decline, which has resulted in calls for the development of an integrated stock management approach. In Oman, the scalloped spiny lobster is currently treated as a single management unit (MU) or stock and there is an absence of information on the genetic population structure of the species that can inform management decisions, particularly at a fine-scale level. This work is the first to identify genome-wide single nucleotide polymorphisms (SNPs) for P. homarus using Diversity Arrays Technology sequencing (DArT-seq) and to elucidate any stock structure in the species.

RESULTS: After stringent filtering, 7988 high utility SNPs were discovered and used to assess the genetic diversity, connectivity and structure of P. homarus populations from Al Ashkharah, Masirah Island, Duqm, Ras Madrakah, Haitam, Ashuwaymiyah, Mirbat and Dhalkut landing sites. Pairwise FST estimates revealed low differentiation among populations (pairwise FST range = - 0.0008 - 0.0021). Analysis of genetic variation using putatively directional FST outliers (504 SNPs) revealed higher and significant pairwise differentiation (p < 0.01) for all locations, with Ashuwaymiyah being the most diverged population (Ashuwaymiyah pairwise FST range = 0.0288-0.0736). Analysis of population structure using Discriminant Analysis of Principal Components (DAPC) revealed a broad admixture among P. homarus, however, Ashuwaymiyah stock appeared to be potentially under local adaptive pressures. Fine scale analysis using Netview R provided further support for the general admixture of P. homarus.

CONCLUSIONS: Findings here suggested that stocks of P. homarus along the Omani coastline are admixed. Yet, fishery managers need to treat the lobster stock from Ashuwaymiyah with caution as it might be subject to local adaptive pressures. We emphasize further study with larger number of samples to confirm the genetic status of the Ashuwaymiyah stock. The approach utilised in this study has high transferability in conservation and management of other marine stocks with similar biological and ecological attributes.}, } @article {pmid30231935, year = {2018}, author = {Rojas Mora, A and Meniri, M and Ciprietti, S and Helfenstein, F}, title = {Is sperm morphology functionally related to sperm swimming ability? A case study in a wild passerine bird with male hierarchies.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {142}, pmid = {30231935}, issn = {1471-2148}, support = {PP00P3_139011//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH)/International ; }, mesh = {Animals ; Female ; *Hierarchy, Social ; Linear Models ; Male ; Phenotype ; Sparrows/*physiology ; Sperm Motility/*physiology ; Spermatozoa/*cytology/*physiology ; }, abstract = {BACKGROUND: Sexual selection continues after copulation via either sperm competition or cryptic female choice, and favors sperm traits that maximize sperm competitiveness. Both sperm swimming velocity and longevity are important determinants of the outcome of sperm competition. Theoretically, sperm morphology can influence sperm velocity at least in three different non-exclusive ways: (i) longer sperm may generate more propelling thrust, (ii) bigger midpieces may produce more energy, and/or (iii) larger flagella or mid-pieces relative to the head size may compensate for the drag forces around the head. A growing number of studies have investigated the relationship of sperm morphology with sperm performance, which remains equivocal at both the inter- and intra-specific levels. Here, we used House Sparrows to test the functional relationship between sperm morphology with sperm velocity and longevity. Based on a previous study showing that sperm swimming ability covaries with social rank, we predicted that -if a functional relationship exists-1) sperm morphology should differ across social ranks, and 2) correlations between sperm morphology and sperm velocity and/or sperm longevity should be constant across social ranks.

RESULTS: We found no differences in sperm morphology across social ranks. Moreover, we found that sperm morphology may be correlated with sperm velocity, but such relationship varied across social ranks. This result contradicts the hypothesis of a functional relationship between sperm morphology and sperm performance. Finally, after experimentally manipulating social ranks, we observed that relationships between sperm morphology and sperm velocity and/or sperm longevity disappeared or changed direction.

CONCLUSIONS: We suggest that in species with internal fertilization, while sperm morphology is likely constrained by the morphology of the female sperm storage organs, selection may act upon physiological traits that enhance sperm performance. Hence, these two selection forces could decouple sperm performance from sperm morphology.}, } @article {pmid30231929, year = {2018}, author = {Peng, J and Wegner, CE and Bei, Q and Liu, P and Liesack, W}, title = {Metatranscriptomics reveals a differential temperature effect on the structural and functional organization of the anaerobic food web in rice field soil.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {169}, pmid = {30231929}, issn = {2049-2618}, abstract = {BACKGROUND: The expected increase in global surface temperature due to climate change may have a tremendous effect on the structure and function of the anaerobic food web in flooded rice field soil. Here, we used the metatranscriptomic analysis of total RNA to gain a system-level understanding of this temperature effect on the methanogenic food web.

RESULTS: Mesophilic (30 °C) and thermophilic (45 °C) food web communities had a modular structure. Family-specific rRNA dynamics indicated that each network module represents a particular function within the food webs. Temperature had a differential effect on all the functional activities, including polymer hydrolysis, syntrophic oxidation of key intermediates, and methanogenesis. This was further evidenced by the temporal expression patterns of total bacterial and archaeal mRNA and of transcripts encoding carbohydrate-active enzymes (CAZymes). At 30 °C, various bacterial phyla contributed to polymer hydrolysis, with Firmicutes decreasing and non-Firmicutes (e.g., Bacteroidetes, Ignavibacteriae) increasing with incubation time. At 45 °C, CAZyme expression was solely dominated by the Firmicutes but, depending on polymer and incubation time, varied on family level. The structural and functional community dynamics corresponded well to process measurements (acetate, propionate, methane). At both temperatures, a major change in food web functionality was linked to the transition from the early to late stage. The mesophilic food web was characterized by gradual polymer breakdown that governed acetoclastic methanogenesis (Methanosarcinaceae) and, with polymer hydrolysis becoming the rate-limiting step, syntrophic propionate oxidation (Christensenellaceae, Peptococcaceae). The thermophilic food web had two activity stages characterized first by polymer hydrolysis and followed by syntrophic oxidation of acetate (Thermoanaerobacteraceae, Heliobacteriaceae, clade OPB54). Hydrogenotrophic Methanocellaceae were the syntrophic methanogen partner, but their population structure differed between the temperatures. Thermophilic temperature promoted proliferation of a new Methanocella ecotype.

CONCLUSIONS: Temperature had a differential effect on the structural and functional continuum in which the methanogenic food web operates. This temperature-induced change in food web functionality may not only be a near-future scenario for rice paddies but also for natural wetlands in the tropics and subtropics.}, } @article {pmid30231921, year = {2018}, author = {Vavourakis, CD and Andrei, AS and Mehrshad, M and Ghai, R and Sorokin, DY and Muyzer, G}, title = {A metagenomics roadmap to the uncultured genome diversity in hypersaline soda lake sediments.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {168}, pmid = {30231921}, issn = {2049-2618}, abstract = {BACKGROUND: Hypersaline soda lakes are characterized by extreme high soluble carbonate alkalinity. Despite the high pH and salt content, highly diverse microbial communities are known to be present in soda lake brines but the microbiome of soda lake sediments received much less attention of microbiologists. Here, we performed metagenomic sequencing on soda lake sediments to give the first extensive overview of the taxonomic diversity found in these complex, extreme environments and to gain novel physiological insights into the most abundant, uncultured prokaryote lineages.

RESULTS: We sequenced five metagenomes obtained from four surface sediments of Siberian soda lakes with a pH 10 and a salt content between 70 and 400 g L-1. The recovered 16S rRNA gene sequences were mostly from Bacteria, even in the salt-saturated lakes. Most OTUs were assigned to uncultured families. We reconstructed 871 metagenome-assembled genomes (MAGs) spanning more than 45 phyla and discovered the first extremophilic members of the Candidate Phyla Radiation (CPR). Five new species of CPR were among the most dominant community members. Novel dominant lineages were found within previously well-characterized functional groups involved in carbon, sulfur, and nitrogen cycling. Moreover, key enzymes of the Wood-Ljungdahl pathway were encoded within at least four bacterial phyla never previously associated with this ancient anaerobic pathway for carbon fixation and dissimilation, including the Actinobacteria.

CONCLUSIONS: Our first sequencing effort of hypersaline soda lake sediment metagenomes led to two important advances. First, we showed the existence and obtained the first genomes of haloalkaliphilic members of the CPR and several hundred other novel prokaryote lineages. The soda lake CPR is a functionally diverse group, but the most abundant organisms in this study are likely fermenters with a possible role in primary carbon degradation. Second, we found evidence for the presence of the Wood-Ljungdahl pathway in many more taxonomic groups than those encompassing known homo-acetogens, sulfate-reducers, and methanogens. Since only few environmental metagenomics studies have targeted sediment microbial communities and never to this extent, we expect that our findings are relevant not only for the understanding of haloalkaline environments but can also be used to set targets for future studies on marine and freshwater sediments.}, } @article {pmid30231900, year = {2018}, author = {Wang, J and Song, L and Jiao, Q and Yang, S and Gao, R and Lu, X and Zhou, G}, title = {Comparative genome analysis of jujube witches'-broom Phytoplasma, an obligate pathogen that causes jujube witches'-broom disease.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {689}, pmid = {30231900}, issn = {1471-2164}, support = {31401718//National Natural Science Foundation of China/ ; BS2013NY012//Excellent Young Scientists of Shandong Province/ ; 31701899//National Natural Science Foundation of China/ ; }, mesh = {Bacterial Proteins/*genetics/metabolism ; DNA, Bacterial/*genetics ; *Genome, Bacterial ; Phytoplasma/*classification/*genetics/isolation & purification/pathogenicity ; Plant Diseases/genetics/*microbiology ; Sequence Analysis, DNA ; Ziziphus/*microbiology ; }, abstract = {BACKGROUND: JWB phytoplasma is a kind of insect-transmitted and uncultivable bacterial plant pathogen causeing a destructive Jujube disease. To date, no genome information about JWB phytoplasma has been published, which hindered its characterization at genomic level. To understand its pathogenicity and ecology, the genome of a JWB phytoplasma isolate jwb-nky was sequenced and compared with other phytoplasmas enabled us to explore the mechanisms of genomic rearrangement.

RESULTS: The complete genome sequence of JWB phytoplasma (jwb-nky) was determined, which consisting of one circular chromosome of 750,803 bp with a GC content of 23.3%. 694 protein-encoding genes, 2 operons for rRNA genes and 31 tRNA genes as well as 4 potential mobile units (PMUs) containing clusters of DNA repeats were identified. Based on PHIbaes analysis, a large number of genes were genome-specific and approximately 13% of JWB phytoplasma genes were predicted to be associated with virulence. Although transporters for maltose, dipeptides/oligopeptides, spermidine/putrescine, cobalt, Mn/Zn and methionine were identified, KEGG pathway analysis revealed the reduced metabolic capabilities of JWB phytoplasma. Comparative genome analyses between JWB phytoplasma and other phytoplasmas shows the occurrence of large-scale gene rearrangements. The low synteny with other phytoplasmas indicated that the expansion of multiple gene families/duplication probably occurred separately after differentiation.

CONCLUSIONS: In this study, the complete genome sequence of a JWB phytoplasma isolate jwb-nky that causing JWB disease was reported for the first time and a number of species-specific genes were identified in the genome. The study enhanced our understandings about genomic basis and the pathogenicity mechanism of this pathogen, which will aid in the development of improved strategies for efficient management of JWB diseases.}, } @article {pmid30231878, year = {2018}, author = {Reimer, C and Rubin, CJ and Sharifi, AR and Ha, NT and Weigend, S and Waldmann, KH and Distl, O and Pant, SD and Fredholm, M and Schlather, M and Simianer, H}, title = {Analysis of porcine body size variation using re-sequencing data of miniature and large pigs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {687}, pmid = {30231878}, issn = {1471-2164}, mesh = {Animals ; *Body Size ; *Chromosomes ; Female ; Haplotypes ; Male ; Molecular Sequence Annotation ; Phenotype ; Phylogeny ; *Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; *Selection, Genetic ; Sequence Analysis, DNA/*veterinary ; Swine ; Swine, Miniature ; Whole Genome Sequencing/*methods ; }, abstract = {BACKGROUND: Domestication has led to substantial phenotypic and genetic variation in domestic animals. In pigs, the size of so called minipigs differs by one order of magnitude compared to breeds of large body size. We used biallelic SNPs identified from re-sequencing data to compare various publicly available wild and domestic populations against two minipig breeds to gain better understanding of the genetic background of the extensive body size variation. We combined two complementary measures, expected heterozygosity and the composite likelihood ratio test implemented in "SweepFinder", to identify signatures of selection in Minipigs. We intersected these sweep regions with a measure of differentiation, namely FST, to remove regions of low variation across pigs. An extraordinary large sweep between 52 and 61 Mb on chromosome X was separately analyzed based on SNP-array data of F2 individuals from a cross of Goettingen Minipigs and large pigs.

RESULTS: Selective sweep analysis identified putative sweep regions for growth and subsequent gene annotation provided a comprehensive set of putative candidate genes. A long swept haplotype on chromosome X, descending from the Goettingen Minipig founders was associated with a reduction of adult body length by 3% in F2 cross-breds.

CONCLUSION: The resulting set of genes in putative sweep regions implies that the genetic background of body size variation in pigs is polygenic rather than mono- or oligogenic. Identified genes suggest alterations in metabolic functions and a possible insulin resistance to contribute to miniaturization. A size QTL located within the sweep on chromosome X, with an estimated effect of 3% on body length, is comparable to the largest known in pigs or other species. The androgen receptor AR, previously known to influence pig performance and carcass traits, is the most obvious potential candidate gene within this region.}, } @article {pmid30231876, year = {2018}, author = {Peng, T and Xu, Y and Zhang, Y}, title = {Comparative genomics of molybdenum utilization in prokaryotes and eukaryotes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {691}, pmid = {30231876}, issn = {1471-2164}, support = {31771407//National Natural Science Foundation of China/ ; 2015A030313555//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Biological Evolution ; Eukaryota/*genetics/metabolism ; Genomics/*methods ; Metalloproteins/*genetics/metabolism ; Molybdenum/*metabolism ; Phylogeny ; Prokaryotic Cells/*metabolism ; Proteome/*metabolism ; }, abstract = {BACKGROUND: Molybdenum (Mo) is an essential micronutrient for almost all biological systems, which holds key positions in several enzymes involved in carbon, nitrogen and sulfur metabolism. In general, this transition metal needs to be coordinated to a unique pterin, thus forming a prosthetic group named molybdenum cofactor (Moco) at the catalytic sites of molybdoenzymes. The biochemical functions of many molybdoenzymes have been characterized; however, comprehensive analyses of the evolution of Mo metabolism and molybdoproteomes are quite limited.

RESULTS: In this study, we analyzed almost 5900 sequenced organisms to examine the occurrence of the Mo utilization trait at the levels of Mo transport system, Moco biosynthetic pathway and molybdoproteins in all three domains of life. A global map of Moco biosynthesis and molybdoproteins has been generated, which shows the most detailed understanding of Mo utilization in prokaryotes and eukaryotes so far. Our results revealed that most prokaryotes and all higher eukaryotes utilize Mo whereas many unicellular eukaryotes such as parasites and most yeasts lost the ability to use this metal. By characterizing the molybdoproteomes of all organisms, we found many new molybdoprotein-rich species, especially in bacteria. A variety of new domain fusions were detected for different molybdoprotein families, suggesting the presence of novel proteins that are functionally linked to molybdoproteins or Moco biosynthesis. Moreover, horizontal gene transfer event involving both the Moco biosynthetic pathway and molybdoproteins was identified. Finally, analysis of the relationship between environmental factors and Mo utilization showed new evolutionary trends of the Mo utilization trait.

CONCLUSIONS: Our data provide new insights into the evolutionary history of Mo utilization in nature.}, } @article {pmid30231871, year = {2018}, author = {Buiate, EAS and Xavier, KV and Moore, N and Torres, MF and Farman, ML and Schardl, CL and Vaillancourt, LJ}, title = {Correction to: A comparative genomic analysis of putative pathogenicity genes in the host-specific sibling species Colletotrichum graminicola and Colletotrichum sublineola.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {686}, pmid = {30231871}, issn = {1471-2164}, abstract = {Following the publication of this article [1], the authors informed us of the following error.}, } @article {pmid30231868, year = {2018}, author = {Bilyk, KT and Vargas-Chacoff, L and Cheng, CC}, title = {Evolution in chronic cold: varied loss of cellular response to heat in Antarctic notothenioid fish.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {143}, pmid = {30231868}, issn = {1471-2148}, support = {ANT-1142158//National Science Foundation (US)/International ; ANT-1341701//National Science Foundation/International ; 15150003//Fondap-IDEAL/International ; }, mesh = {Animals ; Antarctic Regions ; *Biological Evolution ; *Cold Temperature ; Gene Expression Regulation ; Gene Ontology ; Heat-Shock Response/genetics ; *Hot Temperature ; Molecular Chaperones/genetics/metabolism ; Perciformes/genetics/*physiology ; RNA, Messenger/genetics/metabolism ; Sequence Analysis, RNA ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Confined within the freezing Southern Ocean, the Antarctic notothenioids have evolved to become both cold adapted and cold specialized. A marked signature of cold specialization is an apparent loss of the cellular heat shock response (HSR). As the HSR has been examined in very few notothenioid species to-date, it remains unknown whether HSR loss pervades the Antarctic radiation, or whether the broader cellular responses to heat stress has sustained similar loss. Understanding the evolutionary status of these responses in this stenothermal taxon is crucial for evaluating its adaptive potential to ocean warming under climate change.

RESULTS: In this study, we used an acute heat stress protocol followed by RNA-Seq analyses to study the evolution of cellular-wide transcriptional responses to heat stress across three select notothenioid lineages - the basal temperate and nearest non-Antarctic sister species Eleginops maclovinus serving as ancestral proxy, the cryopelagic Pagothenia borchgrevinki and the icefish Chionodraco rastrospinosus representing cold-adapted red-blooded and hemoglobinless Antarctic notothenioids respectively. E. maclovinus displayed robust cellular stress responses including the ER Unfolded Protein Response and the cytosolic HSR, cementing the HSR as a plesiomorphy that preceded Antarctic notothenioid radiation. While the transcriptional response to heat stress was minimal in P. borchgrevinki, C. rastrospinosus exhibited robust responses in the broader cellular networks especially in inflammatory responses despite lacking the classic HSR and UPR.

CONCLUSION: The disparate patterns observed in these two archetypal Antarctic species indicate the evolutionary status in cellular ability to mitigate acute heat stress varies even among Antarctic lineages, which may affect their adaptive potential in coping with a warming world.}, } @article {pmid30231864, year = {2018}, author = {Eberle, J and Dimitrov, D and Valdez-Mondragón, A and Huber, BA}, title = {Microhabitat change drives diversification in pholcid spiders.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {141}, pmid = {30231864}, issn = {1471-2148}, support = {HU 980/11-1//Deutsche Forschungsgemeinschaft/International ; DNRF96//Danmarks Grundforskningsfond/International ; 59//Consejo Nacional de Ciencia y Tecnología/International ; }, mesh = {Animals ; *Biodiversity ; Models, Theoretical ; Phylogeny ; Spiders/*classification ; }, abstract = {BACKGROUND: Microhabitat changes are thought to be among the main drivers of diversification. However, this conclusion is mostly based on studies on vertebrates. Here, we investigate the influence of microhabitat on diversification rates in pholcid spiders (Araneae, Pholcidae). Diversification analyses were conducted in the framework of the largest molecular phylogeny of pholcid spiders to date based on three nuclear and three mitochondrial loci from 600 species representing more than 85% of the currently described pholcid genera.

RESULTS: Assessments of ancestral microhabitat revealed frequent evolutionary change. In particular, within the largest subfamily Pholcinae, numerous changes from near-ground habitats towards leaves and back were found. In general, taxa occupying leaves and large sheltered spaces had higher diversification rates than ground-dwelling taxa. Shifts in speciation rate were found in leaf- and space-dwelling taxa.

CONCLUSIONS: Our analyses result in one of the most comprehensive phylogenies available for a major spider family and provide a framework for any subsequent studies of pholcid spider biology. Diversification analyses strongly suggest that microhabitat is an important factor influencing diversification patterns in pholcid spiders.}, } @article {pmid30231862, year = {2018}, author = {Wang, P and Yang, C and Chen, H and Luo, L and Leng, Q and Li, S and Han, Z and Li, X and Song, C and Zhang, X and Wang, D}, title = {Exploring transcription factors reveals crucial members and regulatory networks involved in different abiotic stresses in Brassica napus L.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {202}, pmid = {30231862}, issn = {1471-2229}, support = {2016YFD0101900//National Key Research and Development Program of China/ ; 61773153//National Natural Science Foundation of China/ ; 31671728//National Natural Science Foundation of China/ ; 17A120002//The Key Scientific Research Projects in Colleges and Universities of Henan/ ; 151100111200//Major science and technology special projects of Henan Province/ ; 172102110005//Henan science and technology research project/ ; yqpy20140049//The Basal Research Fund of Henan University/ ; }, mesh = {Brassica napus/genetics/*physiology ; Chromosome Mapping ; Chromosomes, Plant ; Evolution, Molecular ; Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Genome, Plant ; Multigene Family ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Sequence Analysis, RNA ; Stress, Physiological/*genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {BACKGROUND: Brassica napus (B. napus) encompasses diverse transcription factors (TFs), but thorough identification and characterization of TF families, as well as their transcriptional responsiveness to multifarious stresses are still not clear.

RESULTS: Totally 2167 TFs belonging to five families were genome-widely identified in B. napus, including 518 BnAP2/EREBPs, 252 BnbZIPs, 721 BnMYBs, 398 BnNACs and 278 BnWRKYs, which contained some novel members in comparison with existing results. Sub-genome distributions of BnAP2/EREBPs and BnMYBs indicated that the two families might have suffered from duplication and divergence during evolution. Synteny analysis revealed strong co-linearity between B. napus and its two ancestors, although chromosomal rearrangements have occurred and 85 TFs were lost. About 7.6% and 9.4% TFs of the five families in B. napus were novel genes and conserved genes, which both showed preference on the C sub-genome. RNA-Seq revealed that more than 80% TFs were abiotic stress inducible and 315 crucial differentially expressed genes (DEGs) were screened out. Network analysis revealed that the 315 DEGs are highly co-expressed. The homologous gene network in A. thaliana revealed that a considerable amount of TFs could trigger the differential expression of targeted genes, resulting in a complex clustered network with clusters of genes responsible for targeted stress responsiveness.

CONCLUSIONS: We identified and characterized five TF families in B. napus. Some crucial members and regulatory networks involved in different abiotic stresses have been explored. The investigations deepen our understanding of TFs for stress tolerance in B. napus.}, } @article {pmid30231856, year = {2018}, author = {Fukuda, Y and Hirao, T and Mishima, K and Ohira, M and Hiraoka, Y and Takahashi, M and Watanabe, A}, title = {Transcriptome dynamics of rooting zone and aboveground parts of cuttings during adventitious root formation in Cryptomeria japonica D. Don.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {201}, pmid = {30231856}, issn = {1471-2229}, mesh = {Cryptomeria/*genetics/growth & development ; Energy Metabolism/genetics ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Plant Breeding ; Plant Growth Regulators/genetics/metabolism ; Plant Roots/*genetics/*growth & development ; }, abstract = {BACKGROUND: Adventitious root formation is an essential physiological process for successful propagation of cuttings in various plant species. Because coniferous species are highly heterozygous, propagation of cuttings is of great practical use in breeding. Although various factors influence adventitious root formation, little is known of the associated regulatory mechanisms. Whereas adventitious roots generally form from the base of cuttings, this process is accompanied by physiological changes in leaves, which supply assimilates and metabolites. Herein, we present microarray analyses of transcriptome dynamics during adventitious root formation in whole cuttings in the coniferous species, Cryptomeria japonica.

RESULTS: Temporal patterns of gene expression were determined in the base, the middle, and needles of cuttings at eight time points during adventitious root formation. Global gene expression at the base had diverged from that in the middle by 3-h post-insertion, and changed little in the subsequent 3-days post-insertion, and global gene expression in needles altered characteristically at 3- and 6-weeks post-insertion. In Gene Ontology enrichment analysis of major gene clusters based on hierarchical clustering, the expression profiles of genes related to carbohydrates, plant hormones, and other categories indicated multiple biological changes that were involved in adventitious root formation.

CONCLUSIONS: The present comprehensive transcriptome analyses indicate major transcriptional turning and contribute to the understanding of the biological processes and molecular factors that influence adventitious root formation in C. japonica.}, } @article {pmid30231855, year = {2018}, author = {Zeng, Z and Fu, Y and Guo, D and Wu, Y and Ajayi, OE and Wu, Q}, title = {Bacterial endosymbiont Cardinium cSfur genome sequence provides insights for understanding the symbiotic relationship in Sogatella furcifera host.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {688}, pmid = {30231855}, issn = {1471-2164}, support = {XDB11040400//Chinese Academy of Sciences/ ; 2014CB138405//Ministry of Science and Technology of the People's Republic of China/ ; 31571305//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Bacterial Proteins/*genetics ; Cytophagaceae/*physiology ; *Genome, Bacterial ; Genomics ; Hemiptera/*genetics/growth & development/*microbiology ; Phylogeny ; Symbiosis/*physiology ; }, abstract = {BACKGROUND: Sogatella furcifera is a migratory pest that damages rice plants and causes severe economic losses. Due to its ability to annually migrate long distances, S. furcifera has emerged as a major pest of rice in several Asian countries. Symbiotic relationships of inherited bacteria with terrestrial arthropods have significant implications. The genus Cardinium is present in many types of arthropods, where it influences some host characteristics. We present a report of a newly identified strain of the bacterial endosymbiont Cardinium cSfur in S. furcifera.

RESULT: From the whole genome of S. furcifera previously sequenced by our laboratory, we assembled the whole genome sequence of Cardinium cSfur. The sequence comprised 1,103,593 bp with a GC content of 39.2%. The phylogenetic tree of the Bacteroides phylum to which Cardinium cSfur belongs suggests that Cardinium cSfur is closely related to the other strains (Cardinium cBtQ1 and cEper1) that are members of the Amoebophilaceae family. Genome comparison between the host-dependent endosymbiont including Cardinium cSfur and free-living bacteria revealed that the endosymbiont has a smaller genome size and lower GC content, and has lost some genes related to metabolism because of its special environment, which is similar to the genome pattern observed in other insect symbionts. Cardinium cSfur has limited metabolic capability, which makes it less contributive to metabolic and biosynthetic processes in its host. From our findings, we inferred that, to compensate for its limited metabolic capability, Cardinium cSfur harbors a relatively high proportion of transport proteins, which might act as the hub between it and its host. With its acquisition of the whole operon related to biotin synthesis and glycolysis related genes through HGT event, Cardinium cSfur seems to be undergoing changes while establishing a symbiotic relationship with its host.

CONCLUSION: A novel bacterial endosymbiont strain (Cardinium cSfur) has been discovered. A genomic analysis of the endosymbiont in S. furcifera suggests that its genome has undergone certain changes to facilitate its settlement in the host. The envisaged potential reproduction manipulative ability of the new endosymbiont strain in its S. furcifera host has vital implications in designing eco-friendly approaches to combat the insect pest.}, } @article {pmid30231853, year = {2018}, author = {Robinson, AJ and Tamiru, M and Salby, R and Bolitho, C and Williams, A and Huggard, S and Fisch, E and Unsworth, K and Whelan, J and Lewsey, MG}, title = {AgriSeqDB: an online RNA-Seq database for functional studies of agriculturally relevant plant species.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {200}, pmid = {30231853}, issn = {1471-2229}, mesh = {Crops, Agricultural/*genetics ; *Databases, Genetic ; Internet ; *RNA, Plant ; Sequence Analysis, RNA ; Transcriptome ; User-Computer Interface ; }, abstract = {BACKGROUND: The genome-wide expression profile of genes in different tissues/cell types and developmental stages is a vital component of many functional genomic studies. Transcriptome data obtained by RNA-sequencing (RNA-Seq) is often deposited in public databases that are made available via data portals. Data visualization is one of the first steps in assessment and hypothesis generation. However, these databases do not typically include visualization tools and establishing one is not trivial for users who are not computational experts. This, as well as the various formats in which data is commonly deposited, makes the processes of data access, sharing and utility more difficult. Our goal was to provide a simple and user-friendly repository that meets these needs for data-sets from major agricultural crops.

DESCRIPTION: AgriSeqDB (https://expression.latrobe.edu.au/agriseqdb) is a database for viewing, analysing and interpreting developmental and tissue/cell-specific transcriptome data from several species, including major agricultural crops such as wheat, rice, maize, barley and tomato. The disparate manner in which public transcriptome data is often warehoused and the challenge of visualizing raw data are both major hurdles to data reuse. The popular eFP browser does an excellent job of presenting transcriptome data in an easily interpretable view, but previous implementation has been mostly on a case-by-case basis. Here we present an integrated visualisation database of transcriptome data-sets from six species that did not previously have public-facing visualisations. We combine the eFP browser, for gene-by-gene investigation, with the Degust browser, which enables visualisation of all transcripts across multiple samples. The two visualisation interfaces launch from the same point, enabling users to easily switch between analysis modes. The tools allow users, even those without bioinformatics expertise, to mine into data-sets and understand the behaviour of transcripts of interest across samples and time. We have also incorporated an additional graphic download option to simplify incorporation into presentations or publications.

CONCLUSION: Powered by eFP and Degust browsers, AgriSeqDB is a quick and easy-to-use platform for data analysis and visualization in five crops and Arabidopsis. Furthermore, it provides a tool that makes it easy for researchers to share their data-sets, promoting research collaborations and data-set reuse.}, } @article {pmid30231850, year = {2018}, author = {Goryca, K and Kulecka, M and Paziewska, A and Dabrowska, M and Grzelak, M and Skrzypczak, M and Ginalski, K and Mroz, A and Rutkowski, A and Paczkowska, K and Mikula, M and Ostrowski, J}, title = {Exome scale map of genetic alterations promoting metastasis in colorectal cancer.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {85}, pmid = {30231850}, issn = {1471-2156}, support = {2012/05/D/NZ2/01623//National Science Center/ ; 2015/17/D/NZ2/03711//National Science Center/ ; 2011/02/A/NZ2/00014//National Science Center/ ; TEAM//Foundation for Polish Science/ ; }, abstract = {BACKGROUND: Approximately 90% of colorectal cancer (CRC) deaths are caused by tumors ability to migrate into the adjacent tissues and metastase into distant organs. More than 40 genes have been causally linked to the development of CRC but no mutations have been associated with metastasis yet. To identify molecular basis of CRC metastasis we performed whole-exome and genome-scale transcriptome sequencing of 7 liver metastases along with their matched primary tumours and normal tissue. Multiple, spatially separated fragments of primary tumours were analyzed in each case. Uniformly malignant tissue specimen were selected with macrodissection, for three samples followed with laser microdissection.

RESULTS: > 100 sequencing coverage allowed for detection of genetic alterations in subpopulation of tumour cells. Mutations in KRAS, APC, POLE, and PTPRT, previously associated with CRC development, were detected in most patients. Several new associations were identified, including PLXND1, CELSR3, BAHD1 and PNPLA6.

CONCLUSIONS: We confirm the essential role of inflammation in CRC progression but question the mechanism of matrix metalloproteinases activation described in other work. Comprehensive sequencing data made it possible to associate genome-scale mutation distribution with gene expression patterns. To our knowledge, this is the first work to report such link in CRC metastasis context.}, } @article {pmid30231640, year = {2018}, author = {Arnocky, S and Bozek, E and Dufort, C and Rybka, S and Hebert, R}, title = {Celebrity Opinion Influences Public Acceptance of Human Evolution.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918800656}, doi = {10.1177/1474704918800656}, pmid = {30231640}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Analysis of Variance ; *Attitude ; *Biological Evolution ; *Famous Persons ; Female ; Humans ; Male ; Memory ; Middle Aged ; *Public Opinion ; Sex Factors ; Young Adult ; }, abstract = {The present research examined the influence of celebrity opinion upon individuals' acceptance of the theory of evolution. Priming stimuli were developed purveying pro-evolution, anti-evolution, or neutral opinion (Study 1). When paired with a male celebrity or expert source (Study 2), the male celebrity, but not the male expert, influenced undergraduates' acceptance of evolution. The influence of the male celebrity on acceptance of evolution was replicated in a community sample (Study 3). When paired with a female celebrity source, undergraduates' acceptance of evolution was similarly influenced (Study 4). Together, these findings extend our understanding of the reach of credible celebrity endorsers beyond consumer behavior to core individual beliefs, such as those surrounding the acceptance of human evolution.}, } @article {pmid30231639, year = {2018}, author = {Kim, A and Bradshaw, H and Durante, KM and Hill, SE}, title = {Life History, Fertility, and Short-Term Mating Motivation.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918800062}, doi = {10.1177/1474704918800062}, pmid = {30231639}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Choice Behavior ; Female ; Fertility ; Humans ; Libido ; *Life Change Events ; Menstrual Cycle/psychology ; Middle Aged ; Motivation ; Ovulation/physiology ; Sexual Behavior/physiology/*psychology ; Sexual Partners/*psychology ; Single Person/psychology ; Socioeconomic Factors ; Time Factors ; Women/*psychology ; Young Adult ; }, abstract = {The current research examines the impact of women's early-life socioeconomic status (SES; used as a proxy measure of life history strategy), relationship status, and ovulatory cycle phase on their desire for short-term mating. Results revealed that during the periovulatory phase (i.e., the high-fertility phase of the monthly ovulatory cycle), single women from low SES environments expressed an increased desire for short-term mating, whereas the opposite was found for single women from high SES environments. No such pattern was found for partnered women. These results suggest that one's early-life environment and relationship status may play a key role in how women respond to internal fertility cues, providing important new insights into factors that may moderate ovulatory shifts in mating behavior. Results provide some of the first evidence that one's developmental history may alter the expression of ovulatory cycle adaptations.}, } @article {pmid30230995, year = {2019}, author = {Groeskamp, S and Griffies, SM and Iudicone, D and Marsh, R and Nurser, AJG and Zika, JD}, title = {The Water Mass Transformation Framework for Ocean Physics and Biogeochemistry.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {271-305}, doi = {10.1146/annurev-marine-010318-095421}, pmid = {30230995}, issn = {1941-0611}, abstract = {The water mass transformation (WMT) framework weaves together circulation, thermodynamics, and biogeochemistry into a description of the ocean that complements traditional Eulerian and Lagrangian methods. In so doing, a WMT analysis renders novel insights and predictive capabilities for studies of ocean physics and biogeochemistry. In this review, we describe fundamentals of the WMT framework and illustrate its practical analysis capabilities. We show how it provides a robust methodology to characterize and quantify the impact of physical processes on buoyancy and other thermodynamic fields. We also detail how to extend WMT to insightful analysis of biogeochemical cycles.}, } @article {pmid30230928, year = {2018}, author = {Isaac, RS and McShane, E and Churchman, LS}, title = {The Multiple Levels of Mitonuclear Coregulation.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {511-533}, doi = {10.1146/annurev-genet-120417-031709}, pmid = {30230928}, issn = {1545-2948}, abstract = {Together, the nuclear and mitochondrial genomes encode the oxidative phosphorylation (OXPHOS) complexes that reside in the mitochondrial inner membrane and enable aerobic life. Mitochondria maintain their own genome that is expressed and regulated by factors distinct from their nuclear counterparts. For optimal function, the cell must ensure proper stoichiometric production of OXPHOS subunits by coordinating two physically separated and evolutionarily distinct gene expression systems. Here, we review our current understanding of mitonuclear coregulation primarily at the levels of transcription and translation. Additionally, we discuss other levels of coregulation that may exist but remain largely unexplored, including mRNA modification and stability and posttranslational protein degradation.}, } @article {pmid30230927, year = {2018}, author = {Nachtergaele, S and He, C}, title = {Chemical Modifications in the Life of an mRNA Transcript.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {349-372}, doi = {10.1146/annurev-genet-120417-031522}, pmid = {30230927}, issn = {1545-2948}, abstract = {Investigations over the past eight years of chemical modifications on messenger RNA (mRNA) have revealed a new level of posttranscriptional gene regulation in eukaryotes. Rapid progress in our understanding of these modifications, particularly, N6-methyladenosine (m6A), has revealed their roles throughout the life cycle of an mRNA transcript. m6A methylation provides a rapid mechanism for coordinated transcriptome processing and turnover that is important in embryonic development and cell differentiation. In response to cellular signals, m6A can also regulate the translation of specific pools of transcripts. These mechanisms can be hijacked in human diseases, including numerous cancers and viral infection. Beyond m6A, many other mRNA modifications have been mapped in the transcriptome, but much less is known about their biological functions. As methods continue to be developed, we will be able to study these modifications both more broadly and in greater depth, which will likely reveal a wealth of new RNA biology.}, } @article {pmid30230442, year = {2018}, author = {Tuo, L and Yan, XR and Li, FN and Bao, YX and Shi, HC and Li, HY and Sun, CH}, title = {Brachybacterium endophyticum sp. nov., a novel endophytic actinobacterium isolated from bark of Scutellaria baicalensis Georgi.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3563-3568}, doi = {10.1099/ijsem.0.003032}, pmid = {30230442}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Plant Bark/microbiology ; RNA, Ribosomal, 16S/genetics ; Scutellaria baicalensis/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-positive, aerobic, coccus-shaped, non-spore-forming actinobacterium, designated strain M1HQ-2T, was isolated from a surface-sterilized bark of Scutellaria baicalensis Georgi collected from Guizhou, China and tested using a polyphasic approach to determine its taxonomic position. Strain M1HQ-2T grew at 4-37 °C (optimum, 30 °C), pH 5.0-11.0 (pH 8.0) and in the presence of 0-15 % (w/v) NaCl (1-3 %). Substrate mycelia and aerial mycelia were not formed, and diffusible pigments were not observed on any media tested. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain M1HQ-2T belonged to the genus Brachybacterium and had the highest 16S rRNA gene sequence similarity of 97.6 % to Brachybacteriumsquillarum M-6-3T. Strain M1HQ-2T contained MK-7 as the dominant menaquinone. The cell-wall peptidoglycan contained meso-diaminopimelic acid. The polar lipids profile of strain M1HQ-2T contained diphosphatidylglycerol, phosphatidylglycerol, an unidentified phospholipid and an unidentified lipid. The predominant fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0. The DNA G+C content of strain M1HQ-2T was 71.0 mol%. The average nucleotide identity value between strain M1HQ-2T and type strain of Brachybacterium sacelli was 76.7 %. The estimated DNA-DNA hybridization value between strain M1HQ-2T and type strain of B. sacelli was 20.6 %. On the basis of phylogenetic analysis, chemotaxonomic characteristics and phenotypic data, strain M1HQ-2T represents a novel species of the genus Brachybacterium, for which the name Brachybacteriumendophyticum sp. nov. is proposed. The type strain is M1HQ-2T (=KCTC 49087T=CGMCC 1.16391T).}, } @article {pmid30230441, year = {2018}, author = {Fu, T and Jia, C and Fu, L and Zhou, S and Yao, P and Du, R and Sun, H and Yang, Z and Shi, X and Zhang, XH}, title = {Marinifilum breve sp. nov., a marine bacterium isolated from the Yongle Blue Hole in the South China Sea and emended description of the genus Marinifilum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3540-3545}, doi = {10.1099/ijsem.0.003027}, pmid = {30230441}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Temperature ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, facultative anaerobic, non-motile, short-clavate and non-flagellated marine bacterium strain, designated JC075T, was isolated from the Yongle Blue Hole in the South China Sea. Based on the 16S rRNA gene sequence, strain JC075T was found to be closely related to Marinifilum albidiflavum FB208T (97.10 %), Marinifilum flexuosum DSM 21950T (96.43 %) and Marinifilum fragile JCM 15579T (95.58 %), with less than 90.24 % sequence similarity to other genera of the family Marinifilaceae. The growth temperature was in the range of 10-37 °C, and the optimum temperature was 16 °C. Optimal growth occurred at pH 7.0 and in the presence of 3 % (w/v) NaCl. The isoprenoid quinone of strain JC075T was identified as menaquinone-7 and the predominant fatty acids (>10 %) were iso-C15 : 0 (47.9 %), summed feature 9 (C17 : 1 or/and iso-C17 : 1ω9c; 18.7 %) and iso-C17 : 0 3-OH (14.9 %). The major polar lipids were one phosphatidylethanolamine, one phospholipid, one aminophospholipid, one glycolipid, one aminolipid and two unidentified lipids. The DNA G+C content of strain JC075T was 35.8 mol%. On the basis of polyphasic analysis, strain JC075T was considered to represent a novel species of the genus Marinifilum, for which the name Marinifilumbreve sp. nov. is proposed. The type strain is JC075T (=KCTC 15646T=MCCC 1K03477T=JCM 32401T).}, } @article {pmid30230256, year = {2018}, author = {Kenward, PA and Simister, RL and Morgan-Lang, C and Finke, N and Sturm, A and Hallam, SJ and Crowe, SA}, title = {Recovering cellular biomass from fluids using chemical flocculation.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {686-694}, doi = {10.1111/1758-2229.12690}, pmid = {30230256}, issn = {1758-2229}, abstract = {We developed an efficient, scalable and inexpensive method for recovering cellular biomass from complex fluid matrices that cannot be processed using conventional filtration methods. The method uses chemical flocculation with iron oxyhydroxides, is capable of recovering greater than 90% of cellular biomass from fluids with more than 103 cells ml-1 , and was validated using both mock communities and field samples. High quality DNA can be readily extracted from iron flocs using standard soil extraction kits. We applied chemical flocculation to fracing fluids from British Columbia, Canada and recovered a diversity of microbial taxa including abundant members of the Epsilon- and Deltaproteobacteria previously recovered from shale gas operations in the United States. Application of chemical flocculation presents new opportunities for scalable time-series monitoring and experimentation on complex fluid matrices including microbial community profiling and shotgun metagenomics over gas production well completion cycles.}, } @article {pmid30230082, year = {2018}, author = {Troianou, E and Huisman, J and Pemberton, JM and Walling, CA}, title = {Estimating selection on the act of inbreeding in a population with strong inbreeding depression.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1815-1827}, doi = {10.1111/jeb.13376}, pmid = {30230082}, issn = {1420-9101}, support = {//Wellcome Trust/United Kingdom ; //UK Natural Environment Research Council/ ; //European Research Council/ ; }, abstract = {Inbreeding depression is widely regarded as a driving force in the evolution of dispersal, mate choice and sperm selection. However, due to likely costs of inbreeding avoidance, which are poorly understood, it is unclear to what extent selection to avoid inbreeding is expected in nature. Moreover, there are currently very few empirical estimates of the strength of selection against the act of inbreeding (mating with a relative), as opposed to the fitness costs of being inbred. Here, we use data from the individual-based study of red deer on the Scottish island of Rum, a strongly polygynous system which harbours a large inbreeding load, to estimate selection against the act of inbreeding for each sex. We use pedigree and genomic estimates of relatedness between individuals and measure fitness using both lifetime breeding success (number of calves born) and lifetime reproductive success (number of calves surviving to independence), with the latter incorporating inbreeding depression in calf survival. We find for both sexes that the repeatability of the act of inbreeding was low (< 0.1), suggesting little among-individual variation for this trait on which selection can act. Using the genomic measures, there was significant selection against the act of inbreeding in males, but not in females, and there was considerable uncertainty in the estimate in both sexes. We discuss possible explanations for these patterns and their implications for understanding the evolution of inbreeding avoidance in natural populations.}, } @article {pmid30229886, year = {2018}, author = {Scordato, ESC}, title = {Male competition drives song divergence along an ecological gradient in an avian ring species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2360-2377}, doi = {10.1111/evo.13604}, pmid = {30229886}, issn = {1558-5646}, support = {Lewis and Clark award//American Philosophical Society/ ; Hinds Fund//The University of Chicago/ ; //American Ornithologists' Union/ ; 41102//Division of Environmental Biology/ ; }, abstract = {Sexual selection operates via female choice and male competition, which can act independently, in concert, or in opposition. Female choice is typically considered the stronger selective force, but how these two processes interact to shape phenotypic divergence is poorly understood. I tested the hypothesis that variation in sexual selection in different habitats drives song divergence in the greenish warbler ring species. I evaluated the strength, direction, and targets of female choice and male competition in three populations spanning 2400 km of latitude. Average song length increased with latitude, concomitant with a decline in population density. Within populations, males sang longer songs when females were fertile and shorter songs during territory establishment. Females consistently preferred males with longer songs and larger song repertoires. By contrast, playback experiments showed that males used short songs in territory defense. Songs were shortest at high densities, and in the highest density population only, song traits preferred by females correlated with male territoriality. Stronger male competition at high population densities likely constrains maximum song length, whereas weaker competition at low densities allows expression of female choice for long songs. Interactions between male competition and ecology may be a crucial but oft-overlooked component of phenotypic divergence and speciation.}, } @article {pmid30228342, year = {2018}, author = {Fuller, RA and Wainwright, CE}, title = {Secrets of intercontinental flight.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1523-1524}, doi = {10.1038/s41559-018-0693-1}, pmid = {30228342}, issn = {2397-334X}, } @article {pmid30228334, year = {2018}, author = {Singh Chawla, D}, title = {Huge peer-review study reveals lack of women and non-Westerners.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {295-296}, doi = {10.1038/d41586-018-06678-6}, pmid = {30228334}, issn = {1476-4687}, } @article {pmid30228333, year = {2018}, author = {}, title = {Clever chemistry offers new source of jet fuel.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {286}, doi = {10.1038/d41586-018-06732-3}, pmid = {30228333}, issn = {1476-4687}, } @article {pmid30228332, year = {2018}, author = {Powell, K}, title = {How female scientists can confront gender bias in the workplace.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {421-423}, doi = {10.1038/d41586-018-06697-3}, pmid = {30228332}, issn = {1476-4687}, mesh = {Education, Graduate ; Faculty ; Female ; Humans ; Knowledge ; *Leadership ; Male ; *Mentoring ; Research Personnel/*psychology/statistics & numerical data ; Respect ; Self Concept ; Sex Factors ; Sexism/*prevention & control/*psychology ; *Workplace/psychology/statistics & numerical data ; }, } @article {pmid30228331, year = {2018}, author = {Gordin, MD}, title = {A history of substance.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {306-307}, doi = {10.1038/d41586-018-06696-4}, pmid = {30228331}, issn = {1476-4687}, } @article {pmid30228329, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {319}, doi = {10.1038/d41586-018-06689-3}, pmid = {30228329}, issn = {1476-4687}, } @article {pmid30228328, year = {2018}, author = {Morton, A}, title = {Australia has no climate-change policy - again.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {293-294}, doi = {10.1038/d41586-018-06675-9}, pmid = {30228328}, issn = {1476-4687}, } @article {pmid30228326, year = {2018}, author = {Witze, A}, title = {Stand back, Aquaman: Harpoon-throwing satellite takes aim at space junk.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {297-298}, doi = {10.1038/d41586-018-06674-w}, pmid = {30228326}, issn = {1476-4687}, } @article {pmid30228325, year = {2018}, author = {Gibney, E}, title = {AI helps unlock 'dark matter' of bizarre superconductors.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {294-295}, doi = {10.1038/d41586-018-06144-3}, pmid = {30228325}, issn = {1476-4687}, } @article {pmid30228321, year = {2018}, author = {Maxmen, A}, title = {The hidden lives of deep-sea creatures caught on camera.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {296-297}, doi = {10.1038/d41586-018-06660-2}, pmid = {30228321}, issn = {1476-4687}, } @article {pmid30228295, year = {2018}, author = {Rossi, G and Manfrin, A and Lutolf, MP}, title = {Progress and potential in organoid research.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {671-687}, doi = {10.1038/s41576-018-0051-9}, pmid = {30228295}, issn = {1471-0064}, abstract = {Tissue and organ biology are very challenging to study in mammals, and progress can be hindered, particularly in humans, by sample accessibility and ethical concerns. However, advances in stem cell culture have made it possible to derive in vitro 3D tissues called organoids, which capture some of the key multicellular, anatomical and even functional hallmarks of real organs at the micrometre to millimetre scale. Recent studies have demonstrated that organoids can be used to model organ development and disease and have a wide range of applications in basic research, drug discovery and regenerative medicine. Researchers are now beginning to take inspiration from other fields, such as bioengineering, to generate organoids that are more physiologically relevant and more amenable to real-life applications.}, } @article {pmid30228178, year = {2018}, author = {}, title = {Correction for Chen et al., Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E9025}, doi = {10.1073/pnas.1814741115}, pmid = {30228178}, issn = {1091-6490}, } @article {pmid30228177, year = {2018}, author = {Sluysmans, D and Stoddart, JF}, title = {Growing community of artificial molecular machinists.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9359-9361}, pmid = {30228177}, issn = {1091-6490}, } @article {pmid30228175, year = {2018}, author = {Ornes, S}, title = {News Feature: What's the best way to build a molecular machine?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9327-9330}, pmid = {30228175}, issn = {1091-6490}, mesh = {*Molecular Conformation ; Molecular Motor Proteins/*chemistry ; Molecular Structure ; Nanostructures/*chemistry ; Nanotechnology/*methods/trends ; }, } @article {pmid30228123, year = {2018}, author = {Nguyen, CT and Kurenda, A and Stolz, S and Chételat, A and Farmer, EE}, title = {Identification of cell populations necessary for leaf-to-leaf electrical signaling in a wounded plant.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10178-10183}, pmid = {30228123}, issn = {1091-6490}, mesh = {Arabidopsis/*metabolism ; *Calcium Signaling ; *Membrane Potentials ; *Plant Diseases ; Plant Leaves/*metabolism ; }, abstract = {The identity of the cell files necessary for the leaf-to-leaf transmission of wound signals plants has been debated for decades. In Arabidopsis, wounding initiates the glutamate receptor-like (GLR)-dependent propagation of membrane depolarizations that lead to defense gene activation. Using a vein extraction procedure we found pools of GLR-fusion proteins in endomembranes in phloem sieve elements and/or in xylem contact cells. Strikingly, only double mutants that eliminated GLRs from both of these spatially separated cell types strongly attenuated leaf-to-leaf electrical signaling. glr3.3 mutants were also compromised in their defense against herbivores. Since wounding is known to cause increases in cytosolic calcium, we monitored electrical signals and Ca2+ transients simultaneously. This revealed that wound-induced membrane depolarizations in the wild-type preceded cytosolic Ca2+ maxima. The axial and radial distributions of calcium fluxes were differentially affected in each glr mutant. Resolving a debate over which cell types are necessary for electrical signaling between leaves, we show that phloem sieve elements and xylem contact cells function together in this process.}, } @article {pmid30228122, year = {2018}, author = {Constant, DA and Mateo, R and Nagamine, CM and Kirkegaard, K}, title = {Targeting intramolecular proteinase NS2B/3 cleavages for trans-dominant inhibition of dengue virus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10136-10141}, pmid = {30228122}, issn = {1091-6490}, support = {T32 GM007276/GM/NIGMS NIH HHS/United States ; U19 AI109662/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cricetinae ; Dengue Virus/genetics/*metabolism ; *Proteolysis ; RNA, Viral/*biosynthesis/genetics ; Serine Endopeptidases/genetics/*metabolism ; Viral Nonstructural Proteins/genetics/*metabolism ; }, abstract = {Many positive-strand RNA viruses translate their genomes as single polyproteins that are processed by host and viral proteinases to generate all viral protein products. Among these is dengue virus, which encodes the serine proteinase NS2B/3 responsible for seven different cleavages in the polyprotein. NS2B/3 has been the subject of many directed screens to find chemical inhibitors, of which the compound ARDP0006 is among the most effective at inhibiting viral growth. We show that at least three cleavages in the dengue polyprotein are exclusively intramolecular. By definition, such a cis-acting defect cannot be rescued in trans This creates the possibility that a drug-susceptible or inhibited proteinase can be genetically dominant, inhibiting the outgrowth of drug-resistant virus via precursor accumulation. Indeed, an NS3-G459L variant that is incapable of cleavage at the internal NS3 junction dominantly inhibited negative-strand RNA synthesis of wild-type virus present in the same cell. This internal NS3 cleavage site is the junction most inhibited by ARDP0006, making it likely that the accumulation of toxic precursors, not inhibition of proteolytic activity per se, explains the antiviral efficacy of this compound in restraining viral growth. We argue that intramolecularly cleaving proteinases are promising drug targets for viruses that encode polyproteins. The most effective inhibitors will specifically target cleavage sites required for processing precursors that exert trans-dominant inhibition.}, } @article {pmid30228121, year = {2018}, author = {Rifkin, RA and Huyghe, D and Li, X and Parakala, M and Aisenberg, E and Moss, SJ and Slesinger, PA}, title = {GIRK currents in VTA dopamine neurons control the sensitivity of mice to cocaine-induced locomotor sensitization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9479-E9488}, pmid = {30228121}, issn = {1091-6490}, support = {F30 DA039637/DA/NIDA NIH HHS/United States ; R01 AA018734/AA/NIAAA NIH HHS/United States ; R01 DA037170/DA/NIDA NIH HHS/United States ; T32 GM062754/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cocaine/*toxicity ; Cocaine-Related Disorders/genetics/*metabolism/pathology ; Dopaminergic Neurons/*metabolism/pathology ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/genetics/*metabolism ; Locomotion/*drug effects ; Mice ; Mice, Knockout ; Receptors, Dopamine D2/genetics/metabolism ; Sorting Nexins/genetics/metabolism ; }, abstract = {GABABR-dependent activation of G protein-gated inwardly rectifying potassium channels (GIRK or KIR3) provides a well-known source of inhibition in the brain, but the details on how this important inhibitory pathway affects neural circuits are lacking. We used sorting nexin 27 (SNX27), an endosomal adaptor protein that associates with GIRK2c and GIRK3 subunits, to probe the role of GIRK channels in reward circuits. A conditional knockout of SNX27 in both substantia nigra pars compacta and ventral tegmental area (VTA) dopamine neurons leads to markedly smaller GABABR- and dopamine D2R-activated GIRK currents, as well as to suprasensitivity to cocaine-induced locomotor sensitization. Expression of the SNX27-insensitive GIRK2a subunit in SNX27-deficient VTA dopamine neurons restored GIRK currents and GABABR-dependent inhibition of spike firing, while also resetting the mouse's sensitivity to cocaine-dependent sensitization. These results establish a link between slow inhibition mediated by GIRK channels in VTA dopamine neurons and cocaine addiction, revealing a therapeutic target for treating addiction.}, } @article {pmid30228120, year = {2018}, author = {Wu, YE and Enoki, R and Oda, Y and Huang, ZL and Honma, KI and Honma, S}, title = {Ultradian calcium rhythms in the paraventricular nucleus and subparaventricular zone in the hypothalamus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9469-E9478}, pmid = {30228120}, issn = {1091-6490}, mesh = {Animals ; Brain Waves/drug effects/*physiology ; Calcium Signaling/drug effects/*physiology ; Circadian Clocks/drug effects/*physiology ; GABA-A Receptor Antagonists/pharmacology ; GABAergic Neurons/cytology/*metabolism ; Mice ; Paraventricular Hypothalamic Nucleus/cytology/*physiology ; Tetrodotoxin/pharmacology ; }, abstract = {The suprachiasmatic nucleus (SCN), the master circadian clock in mammals, sends major output signals to the subparaventricular zone (SPZ) and further to the paraventricular nucleus (PVN), the neural mechanism of which is largely unknown. In this study, the intracellular calcium levels were measured continuously in cultured hypothalamic slices containing the PVN, SPZ, and SCN. We detected ultradian calcium rhythms in both the SPZ-PVN and SCN regions with periods of 0.5-4.0 hours, the frequency of which depended on the local circadian rhythm in the SPZ-PVN region. The ultradian rhythms were synchronous in the entire SPZ-PVN region and a part of the SCN. Because the ultradian rhythms were not detected in the SCN-only slice, the origin of ultradian rhythm is the SPZ-PVN region. In association with an ultradian bout, a rapid increase of intracellular calcium in a millisecond order was detected, the frequency of which determined the amplitude of an ultradian bout. The synchronous ultradian rhythms were desynchronized and depressed by a sodium channel blocker tetrodotoxin, suggesting that a tetrodotoxin-sensitive network is involved in synchrony of the ultradian bouts. In contrast, the ultradian rhythm is abolished by glutamate receptor blockers, indicating the critical role of glutamatergic mechanism in ultradian rhythm generation, while a GABAA receptor blocker increased the frequency of ultradian rhythm and modified the circadian rhythm in the SCN. A GABAergic network may refine the circadian output signals. The present study provides a clue to unraveling the loci and network mechanisms of the ultradian rhythm.}, } @article {pmid30228119, year = {2018}, author = {Li, J and Song, E and Chiang, CH and Yu, KJ and Koo, J and Du, H and Zhong, Y and Hill, M and Wang, C and Zhang, J and Chen, Y and Tian, L and Zhong, Y and Fang, G and Viventi, J and Rogers, JA}, title = {Conductively coupled flexible silicon electronic systems for chronic neural electrophysiology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9542-E9549}, pmid = {30228119}, issn = {1091-6490}, mesh = {Electrodes ; *Electrophysiological Phenomena ; *Models, Neurological ; *Silicon ; }, abstract = {Materials and structures that enable long-term, intimate coupling of flexible electronic devices to biological systems are critically important to the development of advanced biomedical implants for biological research and for clinical medicine. By comparison with simple interfaces based on arrays of passive electrodes, the active electronics in such systems provide powerful and sometimes essential levels of functionality; they also demand long-lived, perfect biofluid barriers to prevent corrosive degradation of the active materials and electrical damage to the adjacent tissues. Recent reports describe strategies that enable relevant capabilities in flexible electronic systems, but only for capacitively coupled interfaces. Here, we introduce schemes that exploit patterns of highly doped silicon nanomembranes chemically bonded to thin, thermally grown layers of SiO2 as leakage-free, chronically stable, conductively coupled interfaces. The results can naturally support high-performance, flexible silicon electronic systems capable of amplified sensing and active matrix multiplexing in biopotential recording and in stimulation via Faradaic charge injection. Systematic in vitro studies highlight key considerations in the materials science and the electrical designs for high-fidelity, chronic operation. The results provide a versatile route to biointegrated forms of flexible electronics that can incorporate the most advanced silicon device technologies with broad applications in electrical interfaces to the brain and to other organ systems.}, } @article {pmid30228118, year = {2018}, author = {Wang, X and Pipes, L and Trut, LN and Herbeck, Y and Vladimirova, AV and Gulevich, RG and Kharlamova, AV and Johnson, JL and Acland, GM and Kukekova, AV and Clark, AG}, title = {Genomic responses to selection for tame/aggressive behaviors in the silver fox (Vulpes vulpes).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10398-10403}, pmid = {30228118}, issn = {1091-6490}, support = {R01 GM120782/GM/NIGMS NIH HHS/United States ; }, mesh = {*Aggression ; Animals ; *Behavior, Animal ; Brain/*metabolism ; Foxes/*genetics/psychology ; *Genome ; Genomics ; Male ; Polymorphism, Single Nucleotide ; Russia ; *Selection, Genetic ; *Transcriptome ; }, abstract = {Animal domestication efforts have led to a shared spectrum of striking behavioral and morphological changes. To recapitulate this process, silver foxes have been selectively bred for tame and aggressive behaviors for more than 50 generations at the Institute for Cytology and Genetics in Novosibirsk, Russia. To understand the genetic basis and molecular mechanisms underlying the phenotypic changes, we profiled gene expression levels and coding SNP allele frequencies in two brain tissue specimens from 12 aggressive foxes and 12 tame foxes. Expression analysis revealed 146 genes in the prefrontal cortex and 33 genes in the basal forebrain that were differentially expressed, with a 5% false discovery rate (FDR). These candidates include genes in key pathways known to be critical to neurologic processing, including the serotonin and glutamate receptor pathways. In addition, 295 of the 31,000 exonic SNPs show significant allele frequency differences between the tame and aggressive populations (1% FDR), including genes with a role in neural crest cell fate determination.}, } @article {pmid30228117, year = {2018}, author = {Huang, Z and Zhang, M and Plec, AA and Estill, SJ and Cai, L and Repa, JJ and McKnight, SL and Tu, BP}, title = {ACSS2 promotes systemic fat storage and utilization through selective regulation of genes involved in lipid metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9499-E9506}, pmid = {30228117}, issn = {1091-6490}, support = {R01 CA185169/CA/NCI NIH HHS/United States ; R01 DK078592/DK/NIDDK NIH HHS/United States ; }, mesh = {Acetate-CoA Ligase/genetics/*metabolism ; Acetyl Coenzyme A/genetics/metabolism ; Adipose Tissue/*metabolism/pathology ; Animals ; Fatty Liver/genetics/*metabolism/pathology ; *Gene Expression Regulation ; *Lipid Metabolism ; Liver/*metabolism/pathology ; Mice ; Mice, Knockout ; }, abstract = {Acetyl-CoA synthetase 2 (ACSS2) is a conserved nucleocytosolic enzyme that converts acetate to acetyl-CoA. Adult mice lacking ACSS2 appear phenotypically normal but exhibit reduced tumor burdens in mouse models of liver cancer. The normal physiological functions of this alternate pathway of acetyl-CoA synthesis remain unclear, however. Here, we reveal that mice lacking ACSS2 exhibit a significant reduction in body weight and hepatic steatosis in a diet-induced obesity model. ACSS2 deficiency reduces dietary lipid absorption by the intestine and also perturbs repartitioning and utilization of triglycerides from adipose tissue to the liver due to lowered expression of lipid transporters and fatty acid oxidation genes. In this manner, ACSS2 promotes the systemic storage or metabolism of fat according to the fed or fasted state through the selective regulation of genes involved in lipid metabolism. Thus, targeting ACSS2 may offer a therapeutic benefit for the treatment of fatty liver disease.}, } @article {pmid30228116, year = {2018}, author = {Pishchany, G and Mevers, E and Ndousse-Fetter, S and Horvath, DJ and Paludo, CR and Silva-Junior, EA and Koren, S and Skaar, EP and Clardy, J and Kolter, R}, title = {Amycomicin is a potent and specific antibiotic discovered with a targeted interaction screen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10124-10129}, pmid = {30228116}, issn = {1091-6490}, support = {R01 AI073843/AI/NIAID NIH HHS/United States ; R01 AT009874/AT/NCCIH NIH HHS/United States ; R01 GM058213/GM/NIGMS NIH HHS/United States ; R21 AI117025/AI/NIAID NIH HHS/United States ; }, mesh = {Anthraquinones/chemistry/*pharmacology ; Anti-Bacterial Agents/chemistry/*pharmacology ; DNA, Bacterial/genetics/metabolism ; DNA, Ribosomal/genetics/metabolism ; Microbial Sensitivity Tests/methods ; RNA, Ribosomal, 16S/genetics/metabolism ; Streptomyces coelicolor/genetics/*growth & development ; }, abstract = {The rapid emergence of antibiotic-resistant pathogenic bacteria has accelerated the search for new antibiotics. Many clinically used antibacterials were discovered through culturing a single microbial species under nutrient-rich conditions, but in the environment, bacteria constantly encounter poor nutrient conditions and interact with neighboring microbial species. In an effort to recapitulate this environment, we generated a nine-strain actinomycete community and used 16S rDNA sequencing to deconvolute the stochastic production of antimicrobial activity that was not observed from any of the axenic cultures. We subsequently simplified the community to just two strains and identified Amycolatopsis sp. AA4 as the producing strain and Streptomyces coelicolor M145 as an inducing strain. Bioassay-guided isolation identified amycomicin (AMY), a highly modified fatty acid containing an epoxide isonitrile warhead as a potent and specific inhibitor of Staphylococcus aureus Amycomicin targets an essential enzyme (FabH) in fatty acid biosynthesis and reduces S. aureus infection in a mouse skin-infection model. The discovery of AMY demonstrates the utility of screening complex communities against specific targets to discover small-molecule antibiotics.}, } @article {pmid30228115, year = {2018}, author = {Long, Y and Ren, J and Chen, H}, title = {Intrinsic spin of elastic waves.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9951-9955}, pmid = {30228115}, issn = {1091-6490}, abstract = {Unveiling spins of physical systems usually gives people a fundamental understanding of the geometrical properties of waves from classical to quantum aspects. A great variety of research has shown that transverse waves can possess nontrivial spins and spin-related properties naturally. However, until now, we still lack essential physical insights about the spin nature of longitudinal waves. Here, demonstrated by elastic waves, we uncover spins for longitudinal waves and the mixed longitudinal-transverse waves that play essential roles in spin-momentum locking. Based on this spin perspective, several abnormal phenomena beyond pure transverse waves are attributed to the hybrid spin induced by mixed longitudinal-transverse waves. The unique hybrid spin reveals the complex spin essence in elastic waves and advances our understanding about their fundamental geometrical properties. We also show that these spin-dependent phenomena can be exploited to control the wave propagation, such as nonsymmetric elastic wave excitation by spin pairs, a unidirectional Rayleigh wave, and spin-selected elastic wave routing. These findings are generally applicable for wave cases with longitudinal and transverse components.}, } @article {pmid30228114, year = {2018}, author = {Ghosh, A and Gelbwaser-Klimovsky, D and Niedenzu, W and Lvovsky, AI and Mazets, I and Scully, MO and Kurizki, G}, title = {Two-level masers as heat-to-work converters.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9941-9944}, pmid = {30228114}, issn = {1091-6490}, abstract = {Heat engines, which cyclically transform heat into work, are ubiquitous in technology. Lasers and masers may be viewed as heat engines that rely on population inversion or coherence in the active medium. Here we put forward an unconventional paradigm of a remarkably simple and robust electromagnetic heat-powered engine that bears basic differences to any known maser or laser: The proposed device makes use of only one Raman transition and does not rely on population inversion or coherence in its two-level working medium. Nor does it require any coherent driving. The engine can be powered by the ambient temperature difference between the sky and the ground surface. Its autonomous character and "free" power source make this engine conceptually and technologically enticing.}, } @article {pmid30227897, year = {2018}, author = {Arora-Williams, K and Olesen, SW and Scandella, BP and Delwiche, K and Spencer, SJ and Myers, EM and Abraham, S and Sooklal, A and Preheim, SP}, title = {Dynamics of microbial populations mediating biogeochemical cycling in a freshwater lake.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {165}, pmid = {30227897}, issn = {2049-2618}, abstract = {BACKGROUND: Microbial processes are intricately linked to the depletion of oxygen in in-land and coastal water bodies, with devastating economic and ecological consequences. Microorganisms deplete oxygen during biomass decomposition, degrading the habitat of many economically important aquatic animals. Microbes then turn to alternative electron acceptors, which alter nutrient cycling and generate potent greenhouse gases. As oxygen depletion is expected to worsen with altered land use and climate change, understanding how chemical and microbial dynamics impact dead zones will aid modeling efforts to guide remediation strategies. More work is needed to understand the complex interplay between microbial genes, populations, and biogeochemistry during oxygen depletion.

RESULTS: Here, we used 16S rRNA gene surveys, shotgun metagenomic sequencing, and a previously developed biogeochemical model to identify genes and microbial populations implicated in major biogeochemical transformations in a model lake ecosystem. Shotgun metagenomic sequencing was done for one time point in Aug., 2013, and 16S rRNA gene sequencing was done for a 5-month time series (Mar.-Aug., 2013) to capture the spatiotemporal dynamics of genes and microorganisms mediating the modeled processes. Metagenomic binning analysis resulted in many metagenome-assembled genomes (MAGs) that are implicated in the modeled processes through gene content similarity to cultured organism and the presence of key genes involved in these pathways. The MAGs suggested some populations are capable of methane and sulfide oxidation coupled to nitrate reduction. Using the model, we observe that modulating these processes has a substantial impact on overall lake biogeochemistry. Additionally, 16S rRNA gene sequences from the metagenomic and amplicon libraries were linked to processes through the MAGs. We compared the dynamics of microbial populations in the water column to the model predictions. Many microbial populations involved in primary carbon oxidation had dynamics similar to the model, while those associated with secondary oxidation processes deviated substantially.

CONCLUSIONS: This work demonstrates that the unique capabilities of resident microbial populations will substantially impact the concentration and speciation of chemicals in the water column, unless other microbial processes adjust to compensate for these differences. It further highlights the importance of the biological aspects of biogeochemical processes, such as fluctuations in microbial population dynamics. Integrating gene and population dynamics into biogeochemical models has the potential to improve predictions of the community response under altered scenarios to guide remediation efforts.}, } @article {pmid30227892, year = {2018}, author = {Staley, C and Kaiser, T and Vaughn, BP and Graiziger, CT and Hamilton, MJ and Rehman, TU and Song, K and Khoruts, A and Sadowsky, MJ}, title = {Predicting recurrence of Clostridium difficile infection following encapsulated fecal microbiota transplantation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {166}, pmid = {30227892}, issn = {2049-2618}, support = {R21 AI114722/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent Clostridium difficile infection (rCDI). The use of freeze-dried, encapsulated donor material for FMT (cap-FMT) allows for an easy route of administration and remains clinically effective in the majority of rCDI patients. We hypothesized that specific shifts in the microbiota in response to cap-FMT could predict clinical outcome. We further evaluated the degree of donor microbiota engraftment to determine the extent that donor transfer contributed to recovery.

RESULTS: In total, 89 patients were treated with 100 separate cap-FMTs, with a success rate (no rCDI 60 days post cap-FMT) of 80%. Among responders, the lower alpha diversity (ANOVA P < 0.05) observed among patient's pre-FMT samples was restored following cap-FMT. At 1 week post-FMT, community composition varied by clinical outcome (ANOSIM P < 0.001), with similar abundances among families (Lachnospiraceae, Ruminococcaceae, and Bacteroidaceae) in responder and donor samples. Families that showed differential abundances by outcome (response vs. recurrence) from samples collected 7 days following cap-FMT were used to construct a regression tree-based model to predict recurrence. Results showed a training accuracy of 100% to predict recurrence and the model was 97% accurate against a test data set of samples collected 8-20 days following cap-FMT. Evaluation of the extent of engraftment using the Bayesian algorithm SourceTracker revealed that approximately 50% of the post-FMT communities of responders were attributable to donor microbiota, while an additional 20-30% of the communities were similar to a composite healthy microbiota consisting of all donor samples.

CONCLUSIONS: Regression tree-based analyses of microbial communities identified taxa significantly related to clinical response after 7 days, which can be targeted to improve microbial therapeutics. Furthermore, reinstatement of a healthy assemblage following cap-FMT was only partially attributable to explicit donor engraftment and continued to develop towards an overall healthy assemblage, independent of donor.}, } @article {pmid30227889, year = {2018}, author = {Pereira, CF and Wise, HM and Kurian, D and Pinto, RM and Amorim, MJ and Gill, AC and Digard, P}, title = {Effects of mutations in the effector domain of influenza A virus NS1 protein.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {673}, pmid = {30227889}, issn = {1756-0500}, support = {BBS/E/D/20241864//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/D/20002173//Biotechnology and Biological Sciences Research Council/United Kingdom ; SFRH/BD/60299/2009//Fundação para a Ciência e a Tecnologia/ ; IF/00899/2013//Fundação para a Ciência e a Tecnologia/ ; }, mesh = {Active Transport, Cell Nucleus ; Influenza A virus/*genetics/pathogenicity ; *Mutation ; Protein Binding ; Protein Folding ; RNA, Messenger/metabolism ; Viral Nonstructural Proteins/*genetics ; }, abstract = {OBJECTIVE: The multifunctional NS1 protein of influenza A virus has roles in antagonising cellular innate immune responses and promoting viral gene expression. To better understand the interplay between these functions, we tested the effects of NS1 effector domain mutations known to affect homo-dimerisation or interactions with cellular PI3 kinase or Trim25 on NS1 ability to promote nuclear export of viral mRNAs.

RESULTS: The NS1 dimerisation mutant W187R retained the functions of binding cellular NXF1 as well as stabilising NXF1 interaction with viral segment 7 mRNAs and promoting their nuclear export. Two PI3K-binding mutants, NS1 Y89F and Y89A still bound NXF1 but no longer promoted NXF1 interactions with segment 7 mRNA or its nuclear export. The Trim25-binding mutant NS1 E96A/E97A bound NXF1 and supported NXF1 interactions with segment 7 mRNA but no longer supported mRNA nuclear export. Analysis of WT and mutant NS1 interaction partners identified hsp70 as specifically binding to NS1 E96A/E97A. Whilst these data suggest the possibility of functional links between NS1's effects on intracellular signalling and its role in viral mRNA nuclear export, they also indicate potential pleiotropic effects of the NS1 mutations; in the case of E96A/E97A possibly via disrupted protein folding leading to chaperone recruitment.}, } @article {pmid30227887, year = {2018}, author = {Young, M and Moshood, O and Zhang, J and Sarbacher, CA and Mueller, POE and Halper, J}, title = {Does BMP2 play a role in the pathogenesis of equine degenerative suspensory ligament desmitis?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {672}, pmid = {30227887}, issn = {1756-0500}, mesh = {Animals ; Arthritis ; Bone Morphogenetic Protein 2/*physiology ; Female ; Horse Diseases/*physiopathology ; Horses ; Ligaments ; Male ; Tendons ; Transforming Growth Factor beta/physiology ; }, abstract = {OBJECTIVE: Horses afflicted with degenerative suspensory ligament desmitis (DSLD) suffer from progressive leg pain and lameness without history of trauma. DSLD is a systemic disorder caused by abnormal accumulation of proteoglycans in many connective tissues. One proteoglycan found in higher quantities in DSLD is decorin. The accumulated decorin has an abnormally glycosylated glycosaminoglycan chain in DSLD. In addition to acellular accumulations of proteoglycans foci of active fibroblasts/tenoblasts were observed in some tendons and suspensory ligaments (SLs) from DSLD cases We have hypothesized that this represents an early event in DSLD and that production of chondrogenic growth factors, such as BMP2, and/or enzyme participating in glycosylation of glycosaminoglycans is a major factor in initiation and progression of DSLD.

RESULTS: Using immunohistochemistry we have identified BMP2 in these cellular foci, indicating association with proteoglycan production, but not in other cells in the tendon and SLs. In contrast, very little staining for TGFβ and dermatan sulfate epimerase, an enzyme involved in glycosylation of glycosaminoglycan chains, was observed in these foci and other cells in both control and DSLD-affected tendons and SLs. Our data support our hypothesis that chondrogenic growth factors may be responsible, at least in part for progression of DSLD in horses.}, } @article {pmid30227868, year = {2018}, author = {Li, X and Wu, L and Wang, J and Sun, J and Xia, X and Geng, X and Wang, X and Xu, Z and Xu, Q}, title = {Genome sequencing of rice subspecies and genetic analysis of recombinant lines reveals regional yield- and quality-associated loci.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {102}, pmid = {30227868}, issn = {1741-7007}, abstract = {BACKGROUND: Two of the most widely cultivated rice strains are Oryza sativa indica and O. sativa japonica, and understanding the genetic basis of their agronomic traits is of importance for crop production. These two species are highly distinct in terms of geographical distribution and morphological traits. However, the relationship among genetic background, ecological conditions, and agronomic traits is unclear.

RESULTS: In this study, we performed the de novo assembly of a high-quality genome of SN265, a cultivar that is extensively cultivated as a backbone japonica parent in northern China, using single-molecule sequencing. Recombinant inbred lines (RILs) derived from a cross between SN265 and R99 (indica) were re-sequenced and cultivated in three distinct ecological conditions. We identify 79 QTLs related to 15 agronomic traits. We found that several genes underwent functional alterations when the ecological conditions were changed, and some alleles exhibited contracted responses to different genetic backgrounds. We validated the involvement of one candidate gene, DEP1, in determining panicle length, using CRISPR/Cas9 gene editing.

CONCLUSIONS: This study provides information on the suitable environmental conditions, and genetic background, for functional genes in rice breeding. Moreover, the public availability of the reference genome of northern japonica SN265 provides a valuable resource for plant biologists and the genetic improvement of crops.}, } @article {pmid30227863, year = {2018}, author = {Belicard, T and Jareosettasin, P and Sarkies, P}, title = {The piRNA pathway responds to environmental signals to establish intergenerational adaptation to stress.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {103}, pmid = {30227863}, issn = {1741-7007}, support = {//Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: piRNAs have a constitutive role in genome defence by silencing transposable elements in the germline. In the nematode Caenorhabditis elegans, piRNAs also induce epigenetic silencing of transgenes, which can be maintained for many generations in the absence of the piRNA pathway. The role of multi-generational epigenetic inheritance in adaptation to the environment is unknown.

RESULTS: Here, we show that piRNA biogenesis is downregulated in response to a small increase in temperature. Some effects on gene expression persist into subsequent generations and are associated with a negative fitness cost. We show that simultaneous infection with pathogenic bacteria suppresses downregulation of the piRNA pathway in response to increased temperature. This effect is associated with increased fitness of progeny of infected animals in subsequent generations.

CONCLUSIONS: Our results show that the piRNA pathway integrates inputs from the environment to establish intergenerational responses to environmental conditions, with important consequences for the fitness of the subsequent generation.}, } @article {pmid30227850, year = {2018}, author = {Zhu, K and Liu, H and Chen, X and Cheng, Q and Cheng, ZM}, title = {The kinome of pineapple: catalog and insights into functions in crassulacean acid metabolism plants.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {199}, pmid = {30227850}, issn = {1471-2229}, support = {#1009395//Tennessee Agricultural Experiment Station Project/ ; }, mesh = {Alternative Splicing ; Ananas/*enzymology/genetics/growth & development ; Chromosomes, Plant ; Circadian Rhythm/genetics ; Gene Duplication ; *Gene Expression Regulation, Plant ; Genome, Plant ; Introns ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Protein Domains ; Protein Kinases/*genetics/*metabolism ; }, abstract = {BACKGROUND: Crassulacean acid metabolism (CAM) plants use water 20-80% more efficiently by shifting stomata opening and primary CO2 uptake and fixation to the nighttime. Protein kinases (PKs) play pivotal roles in this biological process. However, few PKs have been functionally analyzed precisely due to their abundance and potential functional redundancy (caused by numerous gene duplications).

RESULTS: In this study, we systematically identified a total of 758 predicted PK genes in the genome of a CAM plant, pineapple (Ananas comosus). The pineapple kinome was classified into 20 groups and 116 families based on the kinase domain sequences. The RLK was the largest group, containing 480 members, and over half of them were predicted to locate at the plasma membrane. Both segmental and tandem duplications make important contributions to the expansion of pineapple kinome based on the synteny analysis. Ka/Ks ratios showed all of the duplication events were under purifying selection. The global expression analysis revealed that pineapple PKs exhibit different tissue-specific and diurnal expression patterns. Forty PK genes in a cluster performed higher expression levels in green leaf tip than in white leaf base, and fourteen of them had strong differential expression patterns between the photosynthetic green leaf tip and the non-photosynthetic white leaf base tissues.

CONCLUSIONS: Our findings provide insights into the evolution and biological function of pineapple PKs and a foundation for further functional analysis of PKs in CAM plants. The gene duplication, expression, and coexpression analysis helped us to rapidly identify the key candidates in pineapple kinome, which may play roles in the carbon fixation process in pineapple and help engineering CAM pathway into C3 crops for improved drought tolerance.}, } @article {pmid30227847, year = {2018}, author = {Farlow, J and Bolkvadze, D and Leshkasheli, L and Kusradze, I and Kotorashvili, A and Kotaria, N and Balarjishvili, N and Kvachadze, L and Nikolich, M and Kutateladze, M}, title = {Genomic characterization of three novel Basilisk-like phages infecting Bacillus anthracis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {685}, pmid = {30227847}, issn = {1471-2164}, mesh = {Bacillus Phages/classification/*genetics ; Bacillus anthracis/*virology ; Evolution, Molecular ; *Genome, Viral ; Genomics/*methods ; Host Specificity ; Phylogeny ; Sequence Analysis, DNA ; Synteny ; Viral Proteins/genetics ; Whole Genome Sequencing/*methods ; }, abstract = {BACKGROUND: In the present study, we sequenced the complete genomes of three novel bacteriophages v_B-Bak1, v_B-Bak6, v_B-Bak10 previously isolated from historical anthrax burial sites in the South Caucasus country of Georgia. We report here major trends in the molecular evolution of these phages, which we designate as "Basilisk-Like-Phages" (BLPs), and illustrate patterns in their evolution, genomic plasticity and core genome architecture.

RESULTS: Comparative whole genome sequence analysis revealed a close evolutionary relationship between our phages and two unclassified Bacillus cereus group phages, phage Basilisk, a broad host range phage (Grose JH et al., J Vir. 2014;88(20):11846-11860) and phage PBC4, a highly host-restricted phage and close relative of Basilisk (Na H. et al. FEMS Microbiol. letters. 2016;363(12)). Genome comparisons of phages v_B-Bak1, v_B-Bak6, and v_B-Bak10 revealed significant similarity in sequence, gene content, and synteny with both Basilisk and PBC4. Transmission electron microscopy (TEM) confirmed the three phages belong to the Siphoviridae family. In contrast to the broad host range of phage Basilisk and the single-strain specificity of PBC4, our three phages displayed host specificity for Bacillus anthracis. Bacillus species including Bacillus cereus, Bacillus subtilis, Bacillus anthracoides, and Bacillus megaterium were refractory to infection.

CONCLUSIONS: Data reported here provide further insight into the shared genomic architecture, host range specificity, and molecular evolution of these rare B. cereus group phages. To date, the three phages represent the only known close relatives of the Basilisk and PBC4 phages and their shared genetic attributes and unique host specificity for B. anthracis provides additional insight into candidate host range determinants.}, } @article {pmid30227846, year = {2018}, author = {Kern, C and Wang, Y and Chitwood, J and Korf, I and Delany, M and Cheng, H and Medrano, JF and Van Eenennaam, AL and Ernst, C and Ross, P and Zhou, H}, title = {Genome-wide identification of tissue-specific long non-coding RNA in three farm animal species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {684}, pmid = {30227846}, issn = {1471-2164}, support = {2015-67015-22940//National Institute of Food and Agriculture/ ; NRSP8//National Institute of Food and Agriculture/ ; NC1170//National Institute of Food and Agriculture/ ; }, mesh = {Animals ; Animals, Domestic/genetics ; Cattle/*genetics ; Chickens/*genetics ; Gene Expression Profiling ; Gene Expression Regulation ; *Genome ; High-Throughput Nucleotide Sequencing ; Male ; Molecular Sequence Annotation ; *Organ Specificity ; RNA, Long Noncoding/*genetics ; Swine/*genetics ; }, abstract = {BACKGROUND: Numerous long non-coding RNAs (lncRNAs) have been identified and their roles in gene regulation in humans, mice, and other model organisms studied; however, far less research has been focused on lncRNAs in farm animal species. While previous studies in chickens, cattle, and pigs identified lncRNAs in specific developmental stages or differentially expressed under specific conditions in a limited number of tissues, more comprehensive identification of lncRNAs in these species is needed. The goal of the FAANG Consortium (Functional Annotation of Animal Genomes) is to functionally annotate animal genomes, including the annotation of lncRNAs. As one of the FAANG pilot projects, lncRNAs were identified across eight tissues in two adult male biological replicates from chickens, cattle, and pigs.

RESULTS: Comprehensive lncRNA annotations for the chicken, cattle, and pig genomes were generated by utilizing RNA-seq from eight tissue types from two biological replicates per species at the adult developmental stage. A total of 9393 lncRNAs in chickens, 7235 lncRNAs in cattle, and 14,429 lncRNAs in pigs were identified. Including novel isoforms and lncRNAs from novel loci, 5288 novel lncRNAs were identified in chickens, 3732 in cattle, and 4870 in pigs. These transcripts match previously known patterns of lncRNAs, such as generally lower expression levels than mRNAs and higher tissue specificity. An analysis of lncRNA conservation across species identified a set of conserved lncRNAs with potential functions associated with chromatin structure and gene regulation. Tissue-specific lncRNAs were identified. Genes proximal to tissue-specific lncRNAs were enriched for GO terms associated with the tissue of origin, such as leukocyte activation in spleen.

CONCLUSIONS: LncRNAs were identified in three important farm animal species using eight tissues from adult individuals. About half of the identified lncRNAs were not previously reported in the NCBI annotations for these species. While lncRNAs are less conserved than protein-coding genes, a set of positionally conserved lncRNAs were identified among chickens, cattle, and pigs with potential functions related to chromatin structure and gene regulation. Tissue-specific lncRNAs have potential regulatory functions on genes enriched for tissue-specific GO terms. Future work will include epigenetic data from ChIP-seq experiments to further refine these annotations.}, } @article {pmid30227829, year = {2018}, author = {Zhou, X and Chan, KCC}, title = {Detecting gene-gene interactions for complex quantitative traits using generalized fuzzy classification.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {329}, pmid = {30227829}, issn = {1471-2105}, mesh = {Animals ; Computational Biology/*methods ; *Epistasis, Genetic ; Female ; *Fuzzy Logic ; Genetic Markers/genetics ; Humans ; Mice ; Models, Genetic ; *Phenotype ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Quantitative traits or continuous outcomes related to complex diseases can provide more information and therefore more accurate analysis for identifying gene-gene and gene- environment interactions associated with complex diseases. Multifactor Dimensionality Reduction (MDR) is originally proposed to identify gene-gene and gene- environment interactions associated with binary status of complex diseases. Some efforts have been made to extend it to quantitative traits (QTs) and ordinal traits. However these and other methods are still not computationally efficient or effective.

RESULTS: Generalized Fuzzy Quantitative trait MDR (GFQMDR) is proposed in this paper to strengthen identification of gene-gene interactions associated with a quantitative trait by first transforming it to an ordinal trait and then selecting best sets of genetic markers, mainly single nucleotide polymorphisms (SNPs) or simple sequence length polymorphic markers (SSLPs), as having strong association with the trait through generalized fuzzy classification using extended member functions. Experimental results on simulated datasets and real datasets show that our algorithm has better success rate, classification accuracy and consistency in identifying gene-gene interactions associated with QTs.

CONCLUSION: The proposed algorithm provides a more effective way to identify gene-gene interactions associated with quantitative traits.}, } @article {pmid30227435, year = {2018}, author = {Priyanka, and Tripathi, V and Raman, R}, title = {Conservation of Ovary-Specific Genes, Foxl2, Aromatase, and Rspo1, in the Common Indian Garden Lizard, Calotes versicolor, That Lacks Chromosomal or Temperature-Dependent Sex Determination.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000491621}, pmid = {30227435}, issn = {1661-5433}, abstract = {Foxl2,Rspo1, and Aromatase are genes important in the ovary developmental pathway in mammals and birds. Here, we show their presence in the lizard, Calotes versicolor, which is known to lack a chromosomal as well as a temperature-dependent mode of sex determination and has an indeterminate, bipotential gonad throughout embryonic development. The expression of the 3 genes, as well as that of CvSox9 and Wnt4 - the known testis and ovary pathway genes - was studied by RT-PCR and whole tissue RNA in situ hybridization (WRISH) on the developing mesonephros gonadal complex (MGC). The expression of all 3 genes was initiated in the gonad shortly after its evagination from the mesonephros (day 5 onwards). CvFoxl2 generally was expressed in those MGCs in which CvSox9 was either not expressed or lowly expressed and vice versa. On the other hand, CvArom was expressed rather sporadically and randomly, showing no association with CvFoxl2, CvRspo1, or CvSox9, though in later stages WRISH preparations showed its coincidence with CvWnt4. CvRspo1 was expressed in almost all embryos right from day 5. Immunofluorescence localization of Rspo1 and Foxl2 proteins showed their presence in the gonads from day 10 onwards, and by day 25 it was primarily confined to the cortex but away from the coelomic epithelium of the gonadal cortex. Apparently both proteins were localized in the pregranulosa cells, Rspo1 in the cytoplasm and Foxl2 in the nucleus. Thus, it is clear that both CvFoxl2 and CvRspo1 are active in ovary formation, but whether they are expressed in the same or different cells is unknown. Though the transcription pattern of CvArom remains circumspect for its role in differentiation of the ovary, earlier evidence on aromatase inhibitor-induced reversal to the male sex indicates its importance in ovary function.}, } @article {pmid30227214, year = {2019}, author = {Cremen, MCM and Leliaert, F and West, J and Lam, DW and Shimada, S and Lopez-Bautista, JM and Verbruggen, H}, title = {Reassessment of the classification of Bryopsidales (Chlorophyta) based on chloroplast phylogenomic analyses.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {397-405}, doi = {10.1016/j.ympev.2018.09.009}, pmid = {30227214}, issn = {1095-9513}, abstract = {The Bryopsidales is a morphologically diverse group of mainly marine green macroalgae characterized by a siphonous structure. The order is composed of three suborders - Ostreobineae, Bryopsidineae, and Halimedineae. While previous studies improved the higher-level classification of the order, the taxonomic placement of some genera in Bryopsidineae (Pseudobryopsis and Lambia) as well as the relationships between the families of Halimedineae remains uncertain. In this study, we re-assess the phylogeny of the order with datasets derived from chloroplast genomes, drastically increasing the taxon sampling by sequencing 32 new chloroplast genomes. The phylogenies presented here provided good support for the major lineages (suborders and most families) in Bryopsidales. In Bryopsidineae, Pseudobryopsis hainanensis was inferred as a distinct lineage from the three established families allowing us to establish the family Pseudobryopsidaceae. The Antarctic species Lambia antarctica was shown to be an early-branching lineage in the family Bryopsidaceae. In Halimedineae, we revealed several inconsistent phylogenetic positions of macroscopic taxa, and several entirely new lineages of microscopic species. A new classification scheme is proposed, which includes the merger of the families Pseudocodiaceae, Rhipiliaceae and Udoteaceae into a more broadly circumscribed Halimedaceae, and the establishment of tribes for the different lineages found therein. In addition, the deep-water genus Johnson-sea-linkia, currently placed in Rhipiliopsis, was reinstated based on our phylogeny.}, } @article {pmid30227119, year = {2018}, author = {Hussein, MM and Mokhtar, DM}, title = {The roles of telocytes in lung development and angiogenesis: An immunohistochemical, ultrastructural, scanning electron microscopy and morphometrical study.}, journal = {Developmental biology}, volume = {443}, number = {2}, pages = {137-152}, doi = {10.1016/j.ydbio.2018.09.010}, pmid = {30227119}, issn = {1095-564X}, mesh = {Angiogenesis Inducing Agents/metabolism ; Animals ; Antigens, CD34/metabolism ; Connexin 43/metabolism ; Immunohistochemistry ; Lung/cytology/*growth & development/metabolism/ultrastructure ; Microscopy, Electron, Scanning ; Phosphopyruvate Hydratase/metabolism ; Rabbits ; Telocytes/cytology/*metabolism ; Telopodes/pathology ; Vascular Endothelial Growth Factor A/metabolism ; Vimentin/metabolism ; }, abstract = {Many studies have been carried out to investigate the occurrence and distribution of telocytes (TCs) in many organs. However, their morphological development is still unclear. This study was performed to demonstrate the morphological development of TCs in rabbits' lung from fetal to postnatal life using light-, electron- microscopy, immunohistochemistry, morphometrical and statistical analysis. During the fetal life, these cells formed an extensive network of telopodes (Tps) which were in close contact with developing alveoli, bronchioles, stem cells and many other interstitial components. In addition, the TCs' number was significantly increased around the neocapillaries in fetal lung. In the fetal life, TCs were stellate in shape and characterized by large cell bodies and many short Tps that contained abundant rER, mitochondria, and ribosomes. By gradual increasing of ages, TCs were spindle in shape with two Tps contained a massive amount of secretory structures (exosomes, ectosomes, and multivesicular bodies). Moreover, TCs in postnatal lung showed a significant decrease in number and diameter of their cell bodies and a significant increase in the length of Tps compared with those in fetal life. The TCs contributed with pneumocytes and endothelium in the formation of air-blood barrier. The TCs' immunohistochemical profiles for CD34, vimentin, c-kit, connexin 43, vascular endothelial growth factor (VEGF), and neuron- specific enolase (NSE) differed between ages during the lung development. This study provided an evidence that TCs contributed to angiogenesis, the formation of the air-blood barrier, lung organization, and development.}, } @article {pmid30226464, year = {2018}, author = {Tanizawa, Y and Tada, I and Kobayashi, H and Endo, A and Maeno, S and Toyoda, A and Arita, M and Nakamura, Y and Sakamoto, M and Ohkuma, M and Tohno, M}, title = {Lactobacillus paragasseri sp. nov., a sister taxon of Lactobacillus gasseri, based on whole-genome sequence analyses.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3512-3517}, doi = {10.1099/ijsem.0.003020}, pmid = {30226464}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; DNA-Directed RNA Polymerases/genetics ; Fatty Acids/chemistry ; *Genome, Bacterial ; Lactobacillus/*classification/genetics ; Lactobacillus gasseri ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Three strains, JCM 5343T, JCM 5344 and JCM 1130, currently identified as Lactobacillus gasseri, were investigated using a polyphasic taxonomic approach. Although these strains shared high 16S rRNA gene sequence similarities with L. gasseri ATCC 33323T (99.9 %), they formed a clade clearly distinct from ATCC 33323T based on whole-genome relatedness. The average nucleotide identity and in silico DNA-DNA hybridization values of these three strains compared to L. gasseri ATCC 33323T were 93.4-93.7 and 53.1-54.1 %, respectively, and both were less than the widely accepted threshold to distinguish two species (95 and 70 %, respectively). The three strains were Gram-stain positive, non-motile, non-spore-forming, catalase-negative and rod-shaped bacteria. They grew at 25-45 °C and in the presence of 2.0 % (w/v) NaCl. The major fatty acids of the three strains were C16 : 0 and C18 : 1 ω9c. Based on phylogenetic analyses of the phenylalanyl-tRNA synthase alpha subunit and RNA polymerase alpha subunit genes, and on phenotypic and chemotaxonomic characteristics, strains JCM 5343T, JCM 5344 and JCM 1130 represent a novel species distinct from L. gasseri, for which we propose the name Lactobacillusparagasseri sp. nov. In addition, a large portion of genomes currently labelled as L. gasseri in the public sequence database should be reclassified as L. paragasseri based on whole-genome relatedness.}, } @article {pmid30226463, year = {2018}, author = {Singh, H and Kaur, M and Singh, S and Mishra, S and Kumar, S and Vemuluri, VR and Tanuku, NRS and Pinnaka, AK}, title = {Salibacterium nitratireducens sp. nov., a haloalkalitolerant bacterium isolated from a water sample from Sambhar salt lake, India.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3506-3511}, doi = {10.1099/ijsem.0.003021}, pmid = {30226463}, issn = {1466-5034}, mesh = {Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; India ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; }, abstract = {A strictly aerobic, haloalkali-tolerant, Gram-stain-positive, non-motile, rod-shaped bacterium, designated strain SMB4T, was isolated from a water sample collected from Sambhar salt lake, Rajasthan, India. Growth occurred at 25-50 °C, 4-12 % (w/v) NaCl and pH of 5-9. Strain SMB4T was positive for β-galactosidase, oxidase, catalase and urease activities. The fatty acids were dominated by branched forms of fatty acids with iso- and anteiso-saturated fatty acids, with a high abundance of anteiso-C15 : 0, anteiso-C17 : 0 and C18 : 0. The cell-wall peptidoglycan of strain SMB4T contained meso-diaminopimelic acid, while the polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and three unidentified lipids. The DNA G+C content of strain SMB4T was 49.1 mol%. A blast sequence similarity search based on 16S rRNA gene sequence indicated that Salibacterium halochares, Salibacterium halotolerans and Salibacterium qingdaonense were the nearest phylogenetic neighbours, with a pair-wise sequence similarities of 98.4, 98.2 and 97.0 % respectively. Phylogenetic analysis showed that strain SMB4T was clustered with S. halochares and together clustered with S. halotolerans and S. qingdaonense. DNA-DNA hybridization of strain SMB4T with S. halochares DSM 21373T, S. halotolerans S7T and S. quigdaonense DSM 21621T showed a relatedness values of only 39.8, 26.3 and 42.8 %, respectively. Based on its phenotypic characteristics and on phylogenetic inference, strain SMB4T represents a novel species of the genus Salibacterium, for which the name Salibacterium nitratireducens sp. nov. is proposed. The type strain is SMB4T (=MTCC 12633T=KCTC 33876T=JCM 32187T).}, } @article {pmid30226461, year = {2018}, author = {Gerritsen, J and Umanets, A and Staneva, I and Hornung, B and Ritari, J and Paulin, L and Rijkers, GT and de Vos, WM and Smidt, H}, title = {Romboutsia hominis sp. nov., the first human gut-derived representative of the genus Romboutsia, isolated from ileostoma effluent.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3479-3486}, doi = {10.1099/ijsem.0.003012}, pmid = {30226461}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Clostridiales/*classification/genetics/isolation & purification ; Cyclopropanes/chemistry ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Humans ; Ileostomy ; Ileum/*microbiology ; Netherlands ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-positive, motile, rod-shaped, obligately anaerobic bacterium, designated FRIFIT, was isolated from human ileostoma effluent and characterized. On the basis of 16S rRNA gene sequence similarity, strain FRIFIT was most closely related to the species Romboutsia ilealis CRIBT (97.7 %), Romboutsia lituseburensis DSM 797T (97.6 %) and Romboutsia sedimentorum LAM201T (96.6 %). The level of DNA-DNA relatedness between strain FRIFIT and R. ilealis CRIBT was 13.9±3.3 % based on DNA-DNA hybridization. Whole genome sequence-based average nucleotide identity between strain FRIFIT and closely related Romboutsia strains ranged from 78.4-79.1 %. The genomic DNA G+C content of strain FRIFIT was 27.8 mol%. The major cellular fatty acids of strain FRIFIT were saturated and unsaturated straight-chain C12-C19 fatty acids as well as cyclopropane fatty acids, with C16 : 0 being the predominant fatty acid. The polar lipid profile comprised five phospholipids and six glycolipids. These results, together with differences in phenotypic features, support the proposal that strain FRIFIT represents a novel species within the genus Romboutsia, for which the name Romboutsiahominis sp. nov. is proposed. The type strain is FRIFIT (=DSM 28814T=KCTC 15553T).}, } @article {pmid30226270, year = {2018}, author = {Caetano, DS and O'Meara, BC and Beaulieu, JM}, title = {Hidden state models improve state-dependent diversification approaches, including biogeographical models.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2308-2324}, doi = {10.1111/evo.13602}, pmid = {30226270}, issn = {1558-5646}, support = {1093/12-6//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, abstract = {The state-dependent speciation and extinction (SSE) models have recently been criticized due to their high rates of "false positive" results. Many researchers have advocated avoiding SSE models in favor of other "nonparametric" or "semiparametric" approaches. The hidden Markov modeling (HMM) approach provides a partial solution to the issues of model adequacy detected with SSE models. The inclusion of "hidden states" can account for rate heterogeneity observed in empirical phylogenies and allows for reliable detection of state-dependent diversification or diversification shifts independent of the trait of interest. However, the adoption of HMM has been hampered by the interpretational challenges of what exactly a "hidden state" represents, which we clarify herein. We show that HMMs in combination with a model-averaging approach naturally account for hidden traits when examining the meaningful impact of a suspected "driver" of diversification. We also extend the HMM to the geographic state-dependent speciation and extinction (GeoSSE) model. We test the efficacy of our "GeoHiSSE" extension with both simulations and an empirical dataset. On the whole, we show that hidden states are a general framework that can distinguish heterogeneous effects of diversification attributed to a focal character.}, } @article {pmid30225897, year = {2018}, author = {Scheiner, SM}, title = {The genetics of phenotypic plasticity. XVI. Interactions among traits and the flow of information.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2292-2307}, doi = {10.1111/evo.13601}, pmid = {30225897}, issn = {1558-5646}, abstract = {Although the environment varies, adaptive trait plasticity is uncommon, which can be due to either costs or limitations. Currently there is little evidence for costs of plasticity; limitations are a more promising explanation, including information reliability. A possible cause for a decrease in information reliability is the channeling of environmental information through one trait that then affects the phenotype of a second trait, the information path. Using an individual-based simulation model, I explored the ways in which configurations of trait interactions and patterns of environmental variation in space and time affect the evolution of phenotypic plasticity. I found that genotypes and phenotypes evolved to shorten and simplify the information path from the environment to fitness. A shortened path was characterized by a decrease in the amount of plasticity for traits that had a less direct connection between the environment of development and fitness. A simplified path was characterized by a decrease in the amount of plasticity for traits that had multiple paths between the environment and their phenotype. These results suggest that an eighth proposition be added to the theory of the evolution of phenotypic plasticity: Trait plasticity will evolve to minimize the information path between the environment and fitness.}, } @article {pmid30225854, year = {2018}, author = {Barth, C and Weiss, MC and Roettger, M and Martin, WF and Unden, G}, title = {Origin and phylogenetic relationships of [4Fe-4S]-containing O2 sensors of bacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4567-4586}, doi = {10.1111/1462-2920.14411}, pmid = {30225854}, issn = {1462-2920}, support = {93046//Volkswagen Foundation/ ; 666053//European Research Council/International ; UN 49/18-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {The advent of environmental O2 about 2.5 billion years ago forced microbes to metabolically adapt and to develop mechanisms for O2 sensing. Sensing of O2 by [4Fe-4S]2+ to [2Fe-2S]2+ cluster conversion represents an ancient mechanism that is used by FNREc (Escherichia coli), FNRBs (Bacillus subtilis), NreBSa (Staphylococcus aureus) and WhiB3Mt (Mycobacterium tuberculosis). The phylogenetic relationship of these sensors was investigated. FNREc homologues are restricted to the proteobacteria and a few representatives from other phyla. Homologues of FNRBs and NreBSa are located within the bacilli, of WhiB3 within the actinobacteria. Archaea contain no homologues. The data reveal no similarity between the FNREc , FNRBs , NreBSa and WhiB3 sensor families on the sequence and structural levels. These O2 sensor families arose independently in phyla that were already present at the time O2 appeared, their members were subsequently distributed by lateral gene transfer. The chemistry of [4Fe-4S] and [2Fe-2S] cluster formation and interconversion appears to be shared by the sensor protein families. The type of signal output is, however, family specific. The homologues of FNREc and NreBSa vary with regard to the number of Cys residues that coordinate the cluster. It is suggested that the variants derive from lateral gene transfer and gained other functions.}, } @article {pmid30225548, year = {2018}, author = {Piégu, B and Arensburger, P and Guillou, F and Bigot, Y}, title = {But where did the centromeres go in the chicken genome models?.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {4}, pages = {297-306}, doi = {10.1007/s10577-018-9585-0}, pmid = {30225548}, issn = {1573-6849}, support = {AviGeS//Conseil Régional du Centre-Val de Loire/ ; 2015//Studium Loire Valley-Institute for Advanced Studies (FR)/ ; }, abstract = {The chicken genome was the third vertebrate to be sequenced. To date, its sequence and feature annotations are used as the reference for avian models in genome sequencing projects developed on birds and other Sauropsida species, and in genetic studies of domesticated birds of economic and evolutionary biology interest. Therefore, an accurate description of this genome model is important to a wide number of scientists. Here, we review the location and features of a very basic element, the centromeres of chromosomes in the galGal5 genome model. Centromeres are elements that are not determined by their DNA sequence but by their epigenetic status, in particular by the accumulation of the histone-like protein CENP-A. Comparison of data from several public sources (primarily marker probes flanking centromeres using fluorescent in situ hybridization done on giant lampbrush chromosomes and CENP-A ChIP-seq datasets) with galGal5 annotations revealed that centromeres are likely inappropriately mapped in 9 of the 16 galGal5 chromosome models in which they are described. Analysis of karyology data confirmed that the location of the main CENP-A peaks in chromosomes is the best means of locating the centromeres in 25 galGal5 chromosome models, the majority of which (16) are fully sequenced and assembled. This data re-analysis reaffirms that several sources of information should be examined to produce accurate genome annotations, particularly for basic structures such as centromeres that are epigenetically determined.}, } @article {pmid30224817, year = {2018}, author = {Dokter, AM and Farnsworth, A and Fink, D and Ruiz-Gutierrez, V and Hochachka, WM and La Sorte, FA and Robinson, OJ and Rosenberg, KV and Kelling, S}, title = {Seasonal abundance and survival of North America's migratory avifauna determined by weather radar.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1603-1609}, doi = {10.1038/s41559-018-0666-4}, pmid = {30224817}, issn = {2397-334X}, abstract = {Avian migration is one of Earth's largest processes of biomass transport, involving billions of birds. We estimated continental biomass flows of nocturnal avian migrants across the contiguous United States using a network of 143 weather radars. We show that, relative to biomass leaving in autumn, proportionally more biomass returned in spring across the southern United States than across the northern United States. Neotropical migrants apparently achieved higher survival during the combined migration and non-breeding period, despite an average three- to fourfold longer migration distance, compared with a more northern assemblage of mostly temperate-wintering migrants. Additional mortality expected with longer migration distances was probably offset by high survival in the (sub)tropics. Nearctic-Neotropical migrants relying on a 'higher survivorship' life-history strategy may be particularly sensitive to variations in survival on the overwintering grounds, highlighting the need to identify and conserve important non-breeding habitats.}, } @article {pmid30224816, year = {2018}, author = {Goss, EM and Timilsina, S}, title = {A bacterial epidemic in wild plants.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1529-1530}, doi = {10.1038/s41559-018-0692-2}, pmid = {30224816}, issn = {2397-334X}, } @article {pmid30224815, year = {2018}, author = {Darroch, SAF and Laflamme, M and Wagner, PJ}, title = {High ecological complexity in benthic Ediacaran communities.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1541-1547}, doi = {10.1038/s41559-018-0663-7}, pmid = {30224815}, issn = {2397-334X}, abstract = {A long-running debate over the affinities of the Neoproterozoic 'Ediacara biota' has led to contrasting interpretations of Ediacaran ecosystem complexity. A 'simple' model assumes that most, if not all, Ediacaran organisms shared similar basic ecologies. A contrasting 'complex' model suggests that the Ediacara biota more likely represent organisms from a variety of different positions on the eukaryotic tree and thus occupied a wide range of different ecologies. We perform a quantitative test of Ediacaran ecosystem complexity using rank abundance distributions (RADs). We show that the Ediacara biota formed complex-type communities throughout much of their stratigraphic range and thus likely comprised species that competed for different resources and/or created niche for others ('ecosystem engineers'). One possible explanation for this pattern rests in the recent inference of multiple metazoan-style feeding modes among the Ediacara biota; in this scenario, different Ediacaran groups/clades were engaged in different methods of nutrient collection and thus competed for different resources. This result illustrates that the Ediacara biota may not have been as bizarre as it is sometimes suggested, and provides an ecological link with the animal-dominated benthic ecosystems of the Palaeozoic era.}, } @article {pmid30224814, year = {2018}, author = {Kissling, WD and Walls, R and Bowser, A and Jones, MO and Kattge, J and Agosti, D and Amengual, J and Basset, A and van Bodegom, PM and Cornelissen, JHC and Denny, EG and Deudero, S and Egloff, W and Elmendorf, SC and Alonso García, E and Jones, KD and Jones, OR and Lavorel, S and Lear, D and Navarro, LM and Pawar, S and Pirzl, R and Rüger, N and Sal, S and Salguero-Gómez, R and Schigel, D and Schulz, KS and Skidmore, A and Guralnick, RP}, title = {Towards global data products of Essential Biodiversity Variables on species traits.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1531-1540}, doi = {10.1038/s41559-018-0667-3}, pmid = {30224814}, issn = {2397-334X}, abstract = {Essential Biodiversity Variables (EBVs) allow observation and reporting of global biodiversity change, but a detailed framework for the empirical derivation of specific EBVs has yet to be developed. Here, we re-examine and refine the previous candidate set of species traits EBVs and show how traits related to phenology, morphology, reproduction, physiology and movement can contribute to EBV operationalization. The selected EBVs express intra-specific trait variation and allow monitoring of how organisms respond to global change. We evaluate the societal relevance of species traits EBVs for policy targets and demonstrate how open, interoperable and machine-readable trait data enable the building of EBV data products. We outline collection methods, meta(data) standardization, reproducible workflows, semantic tools and licence requirements for producing species traits EBVs. An operationalization is critical for assessing progress towards biodiversity conservation and sustainable development goals and has wide implications for data-intensive science in ecology, biogeography, conservation and Earth observation.}, } @article {pmid30224802, year = {2018}, author = {Howard, NC and Marin, ND and Ahmed, M and Rosa, BA and Martin, J and Bambouskova, M and Sergushichev, A and Loginicheva, E and Kurepina, N and Rangel-Moreno, J and Chen, L and Kreiswirth, BN and Klein, RS and Balada-Llasat, JM and Torrelles, JB and Amarasinghe, GK and Mitreva, M and Artyomov, MN and Hsu, FF and Mathema, B and Khader, SA}, title = {Mycobacterium tuberculosis carrying a rifampicin drug resistance mutation reprograms macrophage metabolism through cell wall lipid changes.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1099-1108}, pmid = {30224802}, issn = {2058-5276}, support = {R01 AI123780/AI/NIAID NIH HHS/United States ; R01 AI111914/AI/NIAID NIH HHS/United States ; P30 DK056341/DK/NIDDK NIH HHS/United States ; T32 HL007317/HL/NHLBI NIH HHS/United States ; P41 GM103422/GM/NIGMS NIH HHS/United States ; R01 HL105427/HL/NHLBI NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; P60 DK020579/DK/NIDDK NIH HHS/United States ; U19 AI091036/AI/NIAID NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, abstract = {Tuberculosis is a significant global health threat, with one-third of the world's population infected with its causative agent Mycobacterium tuberculosis (Mtb). The emergence of multidrug-resistant (MDR) Mtb that is resistant to the frontline anti-tubercular drugs rifampicin and isoniazid forces treatment with toxic second-line drugs. Currently, ~4% of new and ~21% of previously treated tuberculosis cases are either rifampicin-drug-resistant or MDR Mtb infections1. The specific molecular host-pathogen interactions mediating the rapid worldwide spread of MDR Mtb strains remain poorly understood. W-Beijing Mtb strains are highly prevalent throughout the world and associated with increased drug resistance2. In the early 1990s, closely related MDR W-Beijing Mtb strains (W strains) were identified in large institutional outbreaks in New York City and caused high mortality rates3. The production of interleukin-1β (IL-1β) by macrophages coincides with the shift towards aerobic glycolysis, a metabolic process that mediates protection against drug-susceptible Mtb4. Here, using a collection of MDR W-Mtb strains, we demonstrate that the overexpression of Mtb cell wall lipids, phthiocerol dimycocerosates, bypasses the interleukin 1 receptor, type I (IL-1R1) signalling pathway, instead driving the induction of interferon-β (IFN-β) to reprogram macrophage metabolism. Importantly, Mtb carrying a drug resistance-conferring single nucleotide polymorphism in rpoB (H445Y)5 can modulate host macrophage metabolic reprogramming. These findings transform our mechanistic understanding of how emerging MDR Mtb strains may acquire drug resistance single nucleotide polymorphisms, thereby altering Mtb surface lipid expression and modulating host macrophage metabolic reprogramming.}, } @article {pmid30224801, year = {2018}, author = {Richardson, RB and Ohlson, MB and Eitson, JL and Kumar, A and McDougal, MB and Boys, IN and Mar, KB and De La Cruz-Rivera, PC and Douglas, C and Konopka, G and Xing, C and Schoggins, JW}, title = {A CRISPR screen identifies IFI6 as an ER-resident interferon effector that blocks flavivirus replication.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1214-1223}, pmid = {30224801}, issn = {2058-5276}, support = {T32 AI005284/AI/NIAID NIH HHS/United States ; UL1 TR001105/TR/NCATS NIH HHS/United States ; T32 AI007520/AI/NIAID NIH HHS/United States ; DP2 AI117922/AI/NIAID NIH HHS/United States ; K01 DK095031/DK/NIDDK NIH HHS/United States ; }, abstract = {The endoplasmic reticulum (ER) is an architecturally diverse organelle that serves as a membrane source for the replication of multiple viruses. Flaviviruses, including yellow fever virus, West Nile virus, dengue virus and Zika virus, induce unique single-membrane ER invaginations that house the viral replication machinery1. Whether this virus-induced ER remodelling is vulnerable to antiviral pathways is unknown. Here, we show that flavivirus replication at the ER is targeted by the interferon (IFN) response. Through genome-scale CRISPR screening, we uncovered an antiviral mechanism mediated by a functional gene pairing between IFI6 (encoding IFN-α-inducible protein 6), an IFN-stimulated gene cloned over 30 years ago2, and HSPA5, which encodes the ER-resident heat shock protein 70 chaperone BiP. We reveal that IFI6 is an ER-localized integral membrane effector that is stabilized through interactions with BiP. Mechanistically, IFI6 prophylactically protects uninfected cells by preventing the formation of virus-induced ER membrane invaginations. Notably, IFI6 has little effect on other mammalian RNA viruses, including the related Flaviviridae family member hepatitis C virus, which replicates in double-membrane vesicles that protrude outwards from the ER. These findings support a model in which the IFN response is armed with a membrane-targeted effector that discriminately blocks the establishment of virus-specific ER microenvironments that are required for replication.}, } @article {pmid30224800, year = {2018}, author = {Te Velthuis, AJW and Long, JC and Bauer, DLV and Fan, RLY and Yen, HL and Sharps, J and Siegers, JY and Killip, MJ and French, H and Oliva-Martín, MJ and Randall, RE and de Wit, E and van Riel, D and Poon, LLM and Fodor, E}, title = {Mini viral RNAs act as innate immune agonists during influenza virus infection.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1234-1242}, pmid = {30224800}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; MR/K000241/1//Medical Research Council/United Kingdom ; }, abstract = {The molecular processes that determine the outcome of influenza virus infection in humans are multifactorial and involve a complex interplay between host, viral and bacterial factors1. However, it is generally accepted that a strong innate immune dysregulation known as 'cytokine storm' contributes to the pathology of infections with the 1918 H1N1 pandemic or the highly pathogenic avian influenza viruses of the H5N1 subtype2-4. The RNA sensor retinoic acid-inducible gene I (RIG-I) plays an important role in sensing viral infection and initiating a signalling cascade that leads to interferon expression5. Here, we show that short aberrant RNAs (mini viral RNAs (mvRNAs)), produced by the viral RNA polymerase during the replication of the viral RNA genome, bind to and activate RIG-I and lead to the expression of interferon-β. We find that erroneous polymerase activity, dysregulation of viral RNA replication or the presence of avian-specific amino acids underlie mvRNA generation and cytokine expression in mammalian cells. By deep sequencing RNA samples from the lungs of ferrets infected with influenza viruses, we show that mvRNAs are generated during infection in vivo. We propose that mvRNAs act as the main agonists of RIG-I during influenza virus infection.}, } @article {pmid30224799, year = {2018}, author = {Sun, H and Kamanova, J and Lara-Tejero, M and Galán, JE}, title = {Salmonella stimulates pro-inflammatory signalling through p21-activated kinases bypassing innate immune receptors.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1122-1130}, pmid = {30224799}, issn = {2058-5276}, support = {R01 AI055472/AI/NIAID NIH HHS/United States ; R01 AI114618/AI/NIAID NIH HHS/United States ; }, abstract = {Microbial infections are most often countered by inflammatory responses that are initiated through the recognition of conserved microbial products by innate immune receptors and result in pathogen expulsion1-6. However, inflammation can also lead to pathology. Tissues such as the intestinal epithelium, which are exposed to microbial products, are therefore subject to stringent negative regulatory mechanisms to prevent signalling through innate immune receptors6-11. This presents a challenge to the enteric pathogen Salmonella Typhimurium, which requires intestinal inflammation to compete against the resident microbiota and to acquire the nutrients and electron acceptors that sustain its replication12,13. We show here that S. Typhimurium stimulates pro-inflammatory signalling by a unique mechanism initiated by effector proteins that are delivered by its type III protein secretion system. These effectors activate Cdc42 and the p21-activated kinase 1 (PAK1) leading to the recruitment of TNF receptor-associated factor 6 (TRAF6) and mitogen-activated protein kinase kinase kinase 7 (TAK1), and the stimulation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inflammatory signalling. The removal of Cdc42, PAK1, TRAF6 or TAK1 prevented S. Typhimurium from stimulating NF-κB signalling in cultured cells. In addition, oral administration of a highly specific PAK inhibitor blocked Salmonella-induced intestinal inflammation and bacterial replication in the mouse intestine, although it resulted in a significant increase in the bacterial loads in systemic tissues. Thus, S. Typhimurium stimulates inflammatory signalling in the intestinal tract by engaging critical downstream signalling components of innate immune receptors. These findings illustrate the unique balance that emerges from host-pathogen co-evolution, in that pathogen-initiated responses that help pathogen replication are also important to prevent pathogen spread to deeper tissues.}, } @article {pmid30224798, year = {2018}, author = {Wang, Q and Guan, Z and Pei, K and Wang, J and Liu, Z and Yin, P and Peng, D and Zou, T}, title = {Structural basis of the arbitrium peptide-AimR communication system in the phage lysis-lysogeny decision.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1266-1273}, doi = {10.1038/s41564-018-0239-y}, pmid = {30224798}, issn = {2058-5276}, abstract = {A bacteriophage can replicate and release virions from a host cell in the lytic cycle or switch to a lysogenic process in which the phage integrates itself into the host genome as a prophage. In Bacillus cells, some types of phages employ the arbitrium communication system, which contains an arbitrium hexapeptide, the cellular receptor AimR and the lysogenic negative regulator AimX. This system controls the decision between the lytic and lysogenic cycles. However, both the mechanism of molecular recognition between the arbitrium peptide and AimR and how downstream gene expression is regulated remain unknown. Here, we report crystal structures for AimR from the SPbeta phage in the apo form and the arbitrium peptide-bound form at 2.20 Å and 1.92 Å, respectively. With or without the peptide, AimR dimerizes through the C-terminal capping helix. AimR assembles a superhelical fold and accommodates the peptide encircled by its tetratricopeptide repeats, which is reminiscent of RRNPP family members from the quorum-sensing system. In the absence of the arbitrium peptide, AimR targets the upstream sequence of the aimX gene; its DNA binding activity is prevented following peptide binding. In summary, our findings provide a structural basis for peptide recognition in the phage lysis-lysogeny decision communication system.}, } @article {pmid30224749, year = {2018}, author = {Kovtun, O and Leneva, N and Bykov, YS and Ariotti, N and Teasdale, RD and Schaffer, M and Engel, BD and Owen, DJ and Briggs, JAG and Collins, BM}, title = {Structure of the membrane-assembled retromer coat determined by cryo-electron tomography.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {561-564}, pmid = {30224749}, issn = {1476-4687}, abstract = {Eukaryotic cells traffic proteins and lipids between different compartments using protein-coated vesicles and tubules. The retromer complex is required to generate cargo-selective tubulovesicular carriers from endosomal membranes1-3. Conserved in eukaryotes, retromer controls the cellular localization and homeostasis of hundreds of transmembrane proteins, and its disruption is associated with major neurodegenerative disorders4-7. How retromer is assembled and how it is recruited to form coated tubules is not known. Here we describe the structure of the retromer complex (Vps26-Vps29-Vps35) assembled on membrane tubules with the bin/amphiphysin/rvs-domain-containing sorting nexin protein Vps5, using cryo-electron tomography and subtomogram averaging. This reveals a membrane-associated Vps5 array, from which arches of retromer extend away from the membrane surface. Vps35 forms the 'legs' of these arches, and Vps29 resides at the apex where it is free to interact with regulatory factors. The bases of the arches connect to each other and to Vps5 through Vps26, and the presence of the same arches on coated tubules within cells confirms their functional importance. Vps5 binds to Vps26 at a position analogous to the previously described cargo- and Snx3-binding site, which suggests the existence of distinct retromer-sorting nexin assemblies. The structure provides insight into the architecture of the coat and its mechanism of assembly, and suggests that retromer promotes tubule formation by directing the distribution of sorting nexin proteins on the membrane surface while providing a scaffold for regulatory-protein interactions.}, } @article {pmid30224748, year = {2018}, author = {Lautenschlager, S and Gill, PG and Luo, ZX and Fagan, MJ and Rayfield, EJ}, title = {The role of miniaturization in the evolution of the mammalian jaw and middle ear.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {533-537}, doi = {10.1038/s41586-018-0521-4}, pmid = {30224748}, issn = {1476-4687}, abstract = {The evolution of the mammalian jaw is one of the most important innovations in vertebrate history, and underpins the exceptional radiation and diversification of mammals over the last 220 million years1,2. In particular, the transformation of the mandible into a single tooth-bearing bone and the emergence of a novel jaw joint-while incorporating some of the ancestral jaw bones into the mammalian middle ear-is often cited as a classic example of the repurposing of morphological structures3,4. Although it is remarkably well-documented in the fossil record, the evolution of the mammalian jaw still poses the paradox of how the bones of the ancestral jaw joint could function both as a joint hinge for powerful load-bearing mastication and as a mandibular middle ear that was delicate enough for hearing. Here we use digital reconstructions, computational modelling and biomechanical analyses to demonstrate that the miniaturization of the early mammalian jaw was the primary driver for the transformation of the jaw joint. We show that there is no evidence for a concurrent reduction in jaw-joint stress and increase in bite force in key non-mammaliaform taxa in the cynodont-mammaliaform transition, as previously thought5-8. Although a shift in the recruitment of the jaw musculature occurred during the evolution of modern mammals, the optimization of mandibular function to increase bite force while reducing joint loads did not occur until after the emergence of the neomorphic mammalian jaw joint. This suggests that miniaturization provided a selective regime for the evolution of the mammalian jaw joint, followed by the integration of the postdentary bones into the mammalian middle ear.}, } @article {pmid30224747, year = {2018}, author = {Yoon, JW and Choi, Y and Hahn, C and Kim, G and Song, SH and Yang, KY and Lee, JY and Kim, Y and Lee, CS and Shin, JK and Lee, HS and Berini, P}, title = {Time-asymmetric loop around an exceptional point over the full optical communications band.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {86-90}, doi = {10.1038/s41586-018-0523-2}, pmid = {30224747}, issn = {1476-4687}, abstract = {Topological operations around exceptional points1-8-time-varying system configurations associated with non-Hermitian singularities-have been proposed as a robust approach to achieving far-reaching open-system dynamics, as demonstrated in highly dissipative microwave transmission3 and cryogenic optomechanical oscillator4 experiments. In stark contrast to conventional systems based on closed-system Hermitian dynamics, environmental interferences at exceptional points are dynamically engaged with their internal coupling properties to create rotational stimuli in fictitious-parameter domains, resulting in chiral systems that exhibit various anomalous physical phenomena9-16. To achieve new wave properties and concomitant device architectures to control them, realizations of such systems in application-abundant technological areas, including communications and signal processing systems, are the next step. However, it is currently unclear whether non-Hermitian interaction schemes can be configured in robust technological platforms for further device engineering. Here we experimentally demonstrate a robust silicon photonic structure with photonic modes that transmit through time-asymmetric loops around an exceptional point in the optical domain. The proposed structure consists of two coupled silicon-channel waveguides and a slab-waveguide leakage-radiation sink that precisely control the required non-Hermitian Hamiltonian experienced by the photonic modes. The fabricated devices generate time-asymmetric light transmission over an extremely broad spectral band covering the entire optical telecommunications window (wavelengths between 1.26 and 1.675 micrometres). Thus, we take a step towards broadband on-chip optical devices based on non-Hermitian topological dynamics by using a semiconductor platform with controllable optoelectronic properties, and towards several potential practical applications, such as on-chip optical isolators and non-reciprocal mode converters. Our results further suggest the technological relevance of non-Hermitian wave dynamics in various other branches of physics, such as acoustics, condensed-matter physics and quantum mechanics.}, } @article {pmid30224746, year = {2018}, author = {Hong, YK and Lacefield, CO and Rodgers, CC and Bruno, RM}, title = {Sensation, movement and learning in the absence of barrel cortex.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {542-546}, pmid = {30224746}, issn = {1476-4687}, support = {R01 NS094659/NS/NINDS NIH HHS/United States ; F32 NS084768/NS/NINDS NIH HHS/United States ; F32 NS096819/NS/NINDS NIH HHS/United States ; R01 NS069679/NS/NINDS NIH HHS/United States ; F31 NS055488/NS/NINDS NIH HHS/United States ; T32 MH015174/MH/NIMH NIH HHS/United States ; }, abstract = {For many of our senses, the role of the cerebral cortex in detecting stimuli is controversial1-17. Here we examine the effects of both acute and chronic inactivation of the primary somatosensory cortex in mice trained to move their large facial whiskers to detect an object by touch and respond with a lever to obtain a water reward. Using transgenic mice, we expressed inhibitory opsins in excitatory cortical neurons. Transient optogenetic inactivation of the primary somatosensory cortex, as well as permanent lesions, initially produced both movement and sensory deficits that impaired detection behaviour, demonstrating the link between sensory and motor systems during active sensing. Unexpectedly, lesioned mice had recovered full behavioural capabilities by the subsequent session. This rapid recovery was experience-dependent, and early re-exposure to the task after lesioning facilitated recovery. Furthermore, ablation of the primary somatosensory cortex before learning did not affect task acquisition. This combined optogenetic and lesion approach suggests that manipulations of the sensory cortex may be only temporarily disruptive to other brain structures that are themselves capable of coordinating multiple, arbitrary movements with sensation. Thus, the somatosensory cortex may be dispensable for active detection of objects in the environment.}, } @article {pmid30224731, year = {2018}, author = {Courtine, G}, title = {Reducing neuronal inhibition restores locomotion in paralysed mice.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {317-318}, doi = {10.1038/d41586-018-06651-3}, pmid = {30224731}, issn = {1476-4687}, mesh = {Animals ; *Locomotion ; Mice ; Nervous System Physiological Phenomena ; *Paralysis ; }, } @article {pmid30224730, year = {2018}, author = {Scheerer, P and Unger, E and Tian, L}, title = {Protein structures guide the design of a much-needed tool for neuroscience.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {312-313}, doi = {10.1038/d41586-018-06670-0}, pmid = {30224730}, issn = {1476-4687}, } @article {pmid30224729, year = {2018}, author = {Abraham, M}, title = {Bird forecasting by radar.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {314}, doi = {10.1038/d41586-018-06688-4}, pmid = {30224729}, issn = {1476-4687}, mesh = {Animals ; *Birds ; Flight, Animal ; Forecasting ; *Radar ; }, } @article {pmid30224728, year = {2018}, author = {Platten, M}, title = {T cells engineered to home in on brain cancer.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {319-320}, doi = {10.1038/d41586-018-05883-7}, pmid = {30224728}, issn = {1476-4687}, mesh = {Brain Neoplasms ; Humans ; Immunotherapy, Adoptive ; *Receptors, Antigen, T-Cell ; *T-Lymphocytes ; }, } @article {pmid30224727, year = {2018}, author = {Lenne, PF and Trivedi, V}, title = {Tissue 'melting' sculpts embryo.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {315-316}, doi = {10.1038/d41586-018-06108-7}, pmid = {30224727}, issn = {1476-4687}, mesh = {Animals ; Embryo, Mammalian ; *Hot Temperature ; Morphogenesis ; *Vertebrates ; }, } @article {pmid30224653, year = {2018}, author = {Evangelou, E and Warren, HR and Mosen-Ansorena, D and Mifsud, B and Pazoki, R and Gao, H and Ntritsos, G and Dimou, N and Cabrera, CP and Karaman, I and Ng, FL and Evangelou, M and Witkowska, K and Tzanis, E and Hellwege, JN and Giri, A and Velez Edwards, DR and Sun, YV and Cho, K and Gaziano, JM and Wilson, PWF and Tsao, PS and Kovesdy, CP and Esko, T and Mägi, R and Milani, L and Almgren, P and Boutin, T and Debette, S and Ding, J and Giulianini, F and Holliday, EG and Jackson, AU and Li-Gao, R and Lin, WY and Luan, J and Mangino, M and Oldmeadow, C and Prins, BP and Qian, Y and Sargurupremraj, M and Shah, N and Surendran, P and Thériault, S and Verweij, N and Willems, SM and Zhao, JH and Amouyel, P and Connell, J and de Mutsert, R and Doney, ASF and Farrall, M and Menni, C and Morris, AD and Noordam, R and Paré, G and Poulter, NR and Shields, DC and Stanton, A and Thom, S and Abecasis, G and Amin, N and Arking, DE and Ayers, KL and Barbieri, CM and Batini, C and Bis, JC and Blake, T and Bochud, M and Boehnke, M and Boerwinkle, E and Boomsma, DI and Bottinger, EP and Braund, PS and Brumat, M and Campbell, A and Campbell, H and Chakravarti, A and Chambers, JC and Chauhan, G and Ciullo, M and Cocca, M and Collins, F and Cordell, HJ and Davies, G and de Borst, MH and de Geus, EJ and Deary, IJ and Deelen, J and Del Greco M, F and Demirkale, CY and Dörr, M and Ehret, GB and Elosua, R and Enroth, S and Erzurumluoglu, AM and Ferreira, T and Frånberg, M and Franco, OH and Gandin, I and Gasparini, P and Giedraitis, V and Gieger, C and Girotto, G and Goel, A and Gow, AJ and Gudnason, V and Guo, X and Gyllensten, U and Hamsten, A and Harris, TB and Harris, SE and Hartman, CA and Havulinna, AS and Hicks, AA and Hofer, E and Hofman, A and Hottenga, JJ and Huffman, JE and Hwang, SJ and Ingelsson, E and James, A and Jansen, R and Jarvelin, MR and Joehanes, R and Johansson, Å and Johnson, AD and Joshi, PK and Jousilahti, P and Jukema, JW and Jula, A and Kähönen, M and Kathiresan, S and Keavney, BD and Khaw, KT and Knekt, P and Knight, J and Kolcic, I and Kooner, JS and Koskinen, S and Kristiansson, K and Kutalik, Z and Laan, M and Larson, M and Launer, LJ and Lehne, B and Lehtimäki, T and Liewald, DCM and Lin, L and Lind, L and Lindgren, CM and Liu, Y and Loos, RJF and Lopez, LM and Lu, Y and Lyytikäinen, LP and Mahajan, A and Mamasoula, C and Marrugat, J and Marten, J and Milaneschi, Y and Morgan, A and Morris, AP and Morrison, AC and Munson, PJ and Nalls, MA and Nandakumar, P and Nelson, CP and Niiranen, T and Nolte, IM and Nutile, T and Oldehinkel, AJ and Oostra, BA and O'Reilly, PF and Org, E and Padmanabhan, S and Palmas, W and Palotie, A and Pattie, A and Penninx, BWJH and Perola, M and Peters, A and Polasek, O and Pramstaller, PP and Nguyen, QT and Raitakari, OT and Ren, M and Rettig, R and Rice, K and Ridker, PM and Ried, JS and Riese, H and Ripatti, S and Robino, A and Rose, LM and Rotter, JI and Rudan, I and Ruggiero, D and Saba, Y and Sala, CF and Salomaa, V and Samani, NJ and Sarin, AP and Schmidt, R and Schmidt, H and Shrine, N and Siscovick, D and Smith, AV and Snieder, H and Sõber, S and Sorice, R and Starr, JM and Stott, DJ and Strachan, DP and Strawbridge, RJ and Sundström, J and Swertz, MA and Taylor, KD and Teumer, A and Tobin, MD and Tomaszewski, M and Toniolo, D and Traglia, M and Trompet, S and Tuomilehto, J and Tzourio, C and Uitterlinden, AG and Vaez, A and van der Most, PJ and van Duijn, CM and Vergnaud, AC and Verwoert, GC and Vitart, V and Völker, U and Vollenweider, P and Vuckovic, D and Watkins, H and Wild, SH and Willemsen, G and Wilson, JF and Wright, AF and Yao, J and Zemunik, T and Zhang, W and Attia, JR and Butterworth, AS and Chasman, DI and Conen, D and Cucca, F and Danesh, J and Hayward, C and Howson, JMM and Laakso, M and Lakatta, EG and Langenberg, C and Melander, O and Mook-Kanamori, DO and Palmer, CNA and Risch, L and Scott, RA and Scott, RJ and Sever, P and Spector, TD and van der Harst, P and Wareham, NJ and Zeggini, E and Levy, D and Munroe, PB and Newton-Cheh, C and Brown, MJ and Metspalu, A and Hung, AM and O'Donnell, CJ and Edwards, TL and Psaty, BM and Tzoulaki, I and Barnes, MR and Wain, LV and Elliott, P and Caulfield, MJ and , }, title = {Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1412-1425}, pmid = {30224653}, issn = {1546-1718}, support = {U01 HG007417/HG/NHGRI NIH HHS/United States ; MC_UU_12015/4//Medical Research Council/United Kingdom ; SP/13/2/30111//British Heart Foundation/United Kingdom ; MC_UU_12015/3//Medical Research Council/United Kingdom ; T32 CA160056/CA/NCI NIH HHS/United States ; MR/L01632X/1//Medical Research Council/United Kingdom ; MC_UU_12015/7//Medical Research Council/United Kingdom ; R01 DK110113/DK/NIDDK NIH HHS/United States ; R01 DK107786/DK/NIDDK NIH HHS/United States ; MR/L01341X/1//Medical Research Council/United Kingdom ; G0601966//Medical Research Council/United Kingdom ; MC_UU_12015/1//Medical Research Council/United Kingdom ; R01 DK062370/DK/NIDDK NIH HHS/United States ; MC_UU_12015/2//Medical Research Council/United Kingdom ; R01 DK101855/DK/NIDDK NIH HHS/United States ; I01 CX000982/CX/CSRD VA/United States ; I01 BX003360/BX/BLRD VA/United States ; MC_UU_12015/5//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; R21 HL121429/HL/NHLBI NIH HHS/United States ; M01 RR000070/RR/NCRR NIH HHS/United States ; U01 DK102163/DK/NIDDK NIH HHS/United States ; }, abstract = {High blood pressure is a highly heritable and modifiable risk factor for cardiovascular disease. We report the largest genetic association study of blood pressure traits (systolic, diastolic and pulse pressure) to date in over 1 million people of European ancestry. We identify 535 novel blood pressure loci that not only offer new biological insights into blood pressure regulation but also highlight shared genetic architecture between blood pressure and lifestyle exposures. Our findings identify new biological pathways for blood pressure regulation with potential for improved cardiovascular disease prevention in the future.}, } @article {pmid30224652, year = {2018}, author = {Smith, JJ and Timoshevskaya, N and Ye, C and Holt, C and Keinath, MC and Parker, HJ and Cook, ME and Hess, JE and Narum, SR and Lamanna, F and Kaessmann, H and Timoshevskiy, VA and Waterbury, CKM and Saraceno, C and Wiedemann, LM and Robb, SMC and Baker, C and Eichler, EE and Hockman, D and Sauka-Spengler, T and Yandell, M and Krumlauf, R and Elgar, G and Amemiya, CT}, title = {Publisher Correction: The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution.}, journal = {Nature genetics}, volume = {50}, number = {11}, pages = {1617}, doi = {10.1038/s41588-018-0199-4}, pmid = {30224652}, issn = {1546-1718}, abstract = {When published, this article did not initially appear open access. This error has been corrected, and the open access status of the paper is noted in all versions of the paper. Additionally, affiliation 16 denoting equal contribution was missing from author Robb Krumlauf in the PDF originally published. This error has also been corrected.}, } @article {pmid30224651, year = {2018}, author = {Li, N and Rowley, SM and Goode, DL and Amarasinghe, KC and McInerny, S and Devereux, L and , and Wong-Brown, MW and Lupat, R and Lee, JEA and Hughes, S and Thompson, ER and Zethoven, M and Li, J and Trainer, AH and Gorringe, KL and Scott, RJ and James, PA and Campbell, IG}, title = {Mutations in RECQL are not associated with breast cancer risk in an Australian population.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1346-1348}, doi = {10.1038/s41588-018-0206-9}, pmid = {30224651}, issn = {1546-1718}, } @article {pmid30224650, year = {2018}, author = {Mas, G and Blanco, E and Ballaré, C and Sansó, M and Spill, YG and Hu, D and Aoi, Y and Le Dily, F and Shilatifard, A and Marti-Renom, MA and Di Croce, L}, title = {Promoter bivalency favors an open chromatin architecture in embryonic stem cells.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1452-1462}, doi = {10.1038/s41588-018-0218-5}, pmid = {30224650}, issn = {1546-1718}, abstract = {In embryonic stem cells (ESCs), developmental gene promoters are characterized by their bivalent chromatin state, with simultaneous modification by MLL2 and Polycomb complexes. Although essential for embryogenesis, bivalency is functionally not well understood. Here, we show that MLL2 plays a central role in ESC genome organization. We generate a catalog of bona fide bivalent genes in ESCs and demonstrate that loss of MLL2 leads to increased Polycomb occupancy. Consequently, promoters lose accessibility, long-range interactions are redistributed, and ESCs fail to differentiate. We pose that bivalency balances accessibility and long-range connectivity of promoters, allowing developmental gene expression to be properly modulated.}, } @article {pmid30224649, year = {2018}, author = {Westra, HJ and Martínez-Bonet, M and Onengut-Gumuscu, S and Lee, A and Luo, Y and Teslovich, N and Worthington, J and Martin, J and Huizinga, T and Klareskog, L and Rantapaa-Dahlqvist, S and Chen, WM and Quinlan, A and Todd, JA and Eyre, S and Nigrovic, PA and Gregersen, PK and Rich, SS and Raychaudhuri, S}, title = {Fine-mapping and functional studies highlight potential causal variants for rheumatoid arthritis and type 1 diabetes.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1366-1374}, doi = {10.1038/s41588-018-0216-7}, pmid = {30224649}, issn = {1546-1718}, support = {R01 AR063759/AR/NIAMS NIH HHS/United States ; U01 HG009088/HG/NHGRI NIH HHS/United States ; UH2 AR067677/AR/NIAMS NIH HHS/United States ; }, abstract = {To define potentially causal variants for autoimmune disease, we fine-mapped1,2 76 rheumatoid arthritis (11,475 cases, 15,870 controls)3 and type 1 diabetes loci (9,334 cases, 11,111 controls)4. After sequencing 799 1-kilobase regulatory (H3K4me3) regions within these loci in 568 individuals, we observed accurate imputation for 89% of common variants. We defined credible sets of ≤5 causal variants at 5 rheumatoid arthritis and 10 type 1 diabetes loci. We identified potentially causal missense variants at DNASE1L3, PTPN22, SH2B3, and TYK2, and noncoding variants at MEG3, CD28-CTLA4, and IL2RA. We also identified potential candidate causal variants at SIRPG and TNFAIP3. Using functional assays, we confirmed allele-specific protein binding and differential enhancer activity for three variants: the CD28-CTLA4 rs117701653 SNP, MEG3 rs34552516 indel, and TNFAIP3 rs35926684 indel.}, } @article {pmid30224648, year = {2018}, author = {Ahmed, H and Lerner-Ellis, J and Cybulski, C and Metcalfe, K and Lubiński, J and Narod, SA and Akbari, MR}, title = {Reply to 'Mutations in RECQL are not associated with breast cancer risk in an Australian population'.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1348-1349}, doi = {10.1038/s41588-018-0233-6}, pmid = {30224648}, issn = {1546-1718}, } @article {pmid30224647, year = {2018}, author = {Basilicata, MF and Bruel, AL and Semplicio, G and Valsecchi, CIK and Aktaş, T and Duffourd, Y and Rumpf, T and Morton, J and Bache, I and Szymanski, WG and Gilissen, C and Vanakker, O and Õunap, K and Mittler, G and van der Burgt, I and El Chehadeh, S and Cho, MT and Pfundt, R and Tan, TY and Kirchhoff, M and Menten, B and Vergult, S and Lindstrom, K and Reis, A and Johnson, DS and Fryer, A and McKay, V and , and Fisher, RB and Thauvin-Robinet, C and Francis, D and Roscioli, T and Pajusalu, S and Radtke, K and Ganesh, J and Brunner, HG and Wilson, M and Faivre, L and Kalscheuer, VM and Thevenon, J and Akhtar, A}, title = {De novo mutations in MSL3 cause an X-linked syndrome marked by impaired histone H4 lysine 16 acetylation.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1442-1451}, doi = {10.1038/s41588-018-0220-y}, pmid = {30224647}, issn = {1546-1718}, abstract = {The etiological spectrum of ultra-rare developmental disorders remains to be fully defined. Chromatin regulatory mechanisms maintain cellular identity and function, where misregulation may lead to developmental defects. Here, we report pathogenic variations in MSL3, which encodes a member of the chromatin-associated male-specific lethal (MSL) complex responsible for bulk histone H4 lysine 16 acetylation (H4K16ac) in flies and mammals. These variants cause an X-linked syndrome affecting both sexes. Clinical features of the syndrome include global developmental delay, progressive gait disturbance, and recognizable facial dysmorphism. MSL3 mutations affect MSL complex assembly and activity, accompanied by a pronounced loss of H4K16ac levels in vivo. Patient-derived cells display global transcriptome alterations of pathways involved in morphogenesis and cell migration. Finally, we use histone deacetylase inhibitors to rebalance acetylation levels, alleviating some of the molecular and cellular phenotypes of patient cells. Taken together, we characterize a syndrome that allowed us to decipher the developmental importance of MSL3 in humans.}, } @article {pmid30224646, year = {2018}, author = {Kirk, JM and Kim, SO and Inoue, K and Smola, MJ and Lee, DM and Schertzer, MD and Wooten, JS and Baker, AR and Sprague, D and Collins, DW and Horning, CR and Wang, S and Chen, Q and Weeks, KM and Mucha, PJ and Calabrese, JM}, title = {Functional classification of long non-coding RNAs by k-mer content.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1474-1482}, pmid = {30224646}, issn = {1546-1718}, support = {R01 GM105785/GM/NIGMS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; T32 GM067553/GM/NIGMS NIH HHS/United States ; R35 GM122532/GM/NIGMS NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; T32 GM007092/GM/NIGMS NIH HHS/United States ; R01 GM121806/GM/NIGMS NIH HHS/United States ; }, abstract = {The functions of most long non-coding RNAs (lncRNAs) are unknown. In contrast to proteins, lncRNAs with similar functions often lack linear sequence homology; thus, the identification of function in one lncRNA rarely informs the identification of function in others. We developed a sequence comparison method to deconstruct linear sequence relationships in lncRNAs and evaluate similarity based on the abundance of short motifs called k-mers. We found that lncRNAs of related function often had similar k-mer profiles despite lacking linear homology, and that k-mer profiles correlated with protein binding to lncRNAs and with their subcellular localization. Using a novel assay to quantify Xist-like regulatory potential, we directly demonstrated that evolutionarily unrelated lncRNAs can encode similar function through different spatial arrangements of related sequence motifs. K-mer-based classification is a powerful approach to detect recurrent relationships between sequence and function in lncRNAs.}, } @article {pmid30224645, year = {2018}, author = {Chiang, CWK and Marcus, JH and Sidore, C and Biddanda, A and Al-Asadi, H and Zoledziewska, M and Pitzalis, M and Busonero, F and Maschio, A and Pistis, G and Steri, M and Angius, A and Lohmueller, KE and Abecasis, GR and Schlessinger, D and Cucca, F and Novembre, J}, title = {Genomic history of the Sardinian population.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1426-1434}, pmid = {30224645}, issn = {1546-1718}, support = {R01 GM108805/GM/NIGMS NIH HHS/United States ; RC2 HG005552/HG/NHGRI NIH HHS/United States ; U01 HG006513/HG/NHGRI NIH HHS/United States ; T32 NS048004/NS/NINDS NIH HHS/United States ; F32 GM106656/GM/NIGMS NIH HHS/United States ; R01 HG007089/HG/NHGRI NIH HHS/United States ; HHSN271201100005C/DA/NIDA NIH HHS/United States ; N01 AG012109/AG/NIA NIH HHS/United States ; T32 GM007197/GM/NIGMS NIH HHS/United States ; R01 HG007022/HG/NHGRI NIH HHS/United States ; U01 HL117626/HL/NHLBI NIH HHS/United States ; R01 HL117626/HL/NHLBI NIH HHS/United States ; RC2 HG005581/HG/NHGRI NIH HHS/United States ; }, abstract = {The population of the Mediterranean island of Sardinia has made important contributions to genome-wide association studies of complex disease traits and, based on ancient DNA studies of mainland Europe, Sardinia is hypothesized to be a unique refuge for early Neolithic ancestry. To provide new insights on the genetic history of this flagship population, we analyzed 3,514 whole-genome sequenced individuals from Sardinia. Sardinian samples show elevated levels of shared ancestry with Basque individuals, especially samples from the more historically isolated regions of Sardinia. Our analysis also uniquely illuminates how levels of genetic similarity with mainland ancient DNA samples varies subtly across the island. Together, our results indicate that within-island substructure and sex-biased processes have substantially impacted the genetic history of Sardinia. These results give new insight into the demography of ancestral Sardinians and help further the understanding of sharing of disease risk alleles between Sardinia and mainland populations.}, } @article {pmid30224644, year = {2018}, author = {Giacomelli, AO and Yang, X and Lintner, RE and McFarland, JM and Duby, M and Kim, J and Howard, TP and Takeda, DY and Ly, SH and Kim, E and Gannon, HS and Hurhula, B and Sharpe, T and Goodale, A and Fritchman, B and Steelman, S and Vazquez, F and Tsherniak, A and Aguirre, AJ and Doench, JG and Piccioni, F and Roberts, CWM and Meyerson, M and Getz, G and Johannessen, CM and Root, DE and Hahn, WC}, title = {Mutational processes shape the landscape of TP53 mutations in human cancer.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1381-1387}, pmid = {30224644}, issn = {1546-1718}, support = {T32 GM007226/GM/NIGMS NIH HHS/United States ; U01 CA199253/CA/NCI NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; U01 CA176058/CA/NCI NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; }, abstract = {Unlike most tumor suppressor genes, the most common genetic alterations in tumor protein p53 (TP53) are missense mutations1,2. Mutant p53 protein is often abundantly expressed in cancers and specific allelic variants exhibit dominant-negative or gain-of-function activities in experimental models3-8. To gain a systematic view of p53 function, we interrogated loss-of-function screens conducted in hundreds of human cancer cell lines and performed TP53 saturation mutagenesis screens in an isogenic pair of TP53 wild-type and null cell lines. We found that loss or dominant-negative inhibition of wild-type p53 function reliably enhanced cellular fitness. By integrating these data with the Catalog of Somatic Mutations in Cancer (COSMIC) mutational signatures database9,10, we developed a statistical model that describes the TP53 mutational spectrum as a function of the baseline probability of acquiring each mutation and the fitness advantage conferred by attenuation of p53 activity. Collectively, these observations show that widely-acting and tissue-specific mutational processes combine with phenotypic selection to dictate the frequencies of recurrent TP53 mutations.}, } @article {pmid30224643, year = {2018}, author = {Orlando, G and Law, PJ and Cornish, AJ and Dobbins, SE and Chubb, D and Broderick, P and Litchfield, K and Hariri, F and Pastinen, T and Osborne, CS and Taipale, J and Houlston, RS}, title = {Promoter capture Hi-C-based identification of recurrent noncoding mutations in colorectal cancer.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1375-1380}, doi = {10.1038/s41588-018-0211-z}, pmid = {30224643}, issn = {1546-1718}, abstract = {Efforts are being directed to systematically analyze the non-coding regions of the genome for cancer-driving mutations1-6. cis-regulatory elements (CREs) represent a highly enriched subset of the non-coding regions of the genome in which to search for such mutations. Here we use high-throughput chromosome conformation capture techniques (Hi-C) for 19,023 promoter fragments to catalog the regulatory landscape of colorectal cancer in cell lines, mapping CREs and integrating these with whole-genome sequence and expression data from The Cancer Genome Atlas7,8. We identify a recurrently mutated CRE interacting with the ETV1 promoter affecting gene expression. ETV1 expression influences cell viability and is associated with patient survival. We further refine our understanding of the regulatory effects of copy-number variations, showing that RASL11A is targeted by a previously identified enhancer amplification1. This study reveals new insights into the complex genetic alterations driving tumor development, providing a paradigm for employing chromosome conformation capture to decipher non-coding CREs relevant to cancer biology.}, } @article {pmid30224498, year = {2018}, author = {Moore, YE and Deeb, TZ and Chadchankar, H and Brandon, NJ and Moss, SJ}, title = {Potentiating KCC2 activity is sufficient to limit the onset and severity of seizures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10166-10171}, pmid = {30224498}, issn = {1091-6490}, support = {R01 NS087662/NS/NINDS NIH HHS/United States ; R01 MH097446/MH/NIMH NIH HHS/United States ; R01 DA037170/DA/NIDA NIH HHS/United States ; R21 MH106954/MH/NIMH NIH HHS/United States ; R01 NS101888/NS/NINDS NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Animals ; Epilepsy/genetics/*metabolism/pathology ; Gene Knock-In Techniques ; Mice ; Mutation, Missense ; Neurons/*metabolism/pathology ; Seizures/genetics/*metabolism/pathology ; Symporters/genetics/*metabolism ; Synaptic Membranes/genetics/*metabolism/pathology ; gamma-Aminobutyric Acid/genetics/*metabolism ; }, abstract = {The type 2 K+/Cl- cotransporter (KCC2) allows neurons to maintain low intracellular levels of Cl-, a prerequisite for efficient synaptic inhibition. Reductions in KCC2 activity are evident in epilepsy; however, whether these deficits directly contribute to the underlying pathophysiology remains controversial. To address this issue, we created knock-in mice in which threonines 906 and 1007 within KCC2 have been mutated to alanines (KCC2-T906A/T1007A), which prevents its phospho-dependent inactivation. The respective mice appeared normal and did not show any overt phenotypes, and basal neuronal excitability was unaffected. KCC2-T906A/T1007A mice exhibited increased basal neuronal Cl- extrusion, without altering total or plasma membrane accumulation of KCC2. Critically, activity-induced deficits in synaptic inhibition were reduced in the mutant mice. Consistent with this, enhanced KCC2 was sufficient to limit chemoconvulsant-induced epileptiform activity. Furthermore, this increase in KCC2 function mitigated induction of aberrant high-frequency activity during seizures, highlighting depolarizing GABA as a key contributor to the pathological neuronal synchronization seen in epilepsy. Thus, our results demonstrate that potentiating KCC2 represents a therapeutic strategy to alleviate seizures.}, } @article {pmid30224497, year = {2018}, author = {Yang, CL and Zhang, B and Charness, G and Li, C and Lien, JW}, title = {Endogenous rewards promote cooperation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9968-9973}, pmid = {30224497}, issn = {1091-6490}, mesh = {*Cooperative Behavior ; Humans ; *Models, Economic ; *Reward ; }, abstract = {Sustaining cooperation in social dilemmas is a fundamental objective in the social and biological sciences. Although providing a punishment option to community members in the public goods game (PGG) has been shown to effectively promote cooperation, this has some serious disadvantages; these include destruction of a society's physical resources as well as its overall social capital. A more efficient approach may be to instead employ a reward mechanism. We propose an endogenous reward mechanism that taxes the gross income of each round's PGG play and assigns the amount to a fund; each player then decides how to distribute his or her share of the fund as rewards to other members of the community. Our mechanism successfully reverses the decay trend and achieves a high level of contribution with budget-balanced rewards that require no external funding, an important condition for practical implementation. Simulations based on type-specific estimations indicate that the payoff-based conditional cooperation model explains the observed treatment effects well.}, } @article {pmid30224496, year = {2018}, author = {Mukherjee, S and Moustafa, DA and Stergioula, V and Smith, CD and Goldberg, JB and Bassler, BL}, title = {The PqsE and RhlR proteins are an autoinducer synthase-receptor pair that control virulence and biofilm development in Pseudomonas aeruginosa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9411-E9418}, pmid = {30224496}, issn = {1091-6490}, support = {R37 GM065859/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Biofilms/*growth & development ; Pseudomonas aeruginosa/*pathogenicity/*physiology ; Quorum Sensing/*physiology ; Thiolester Hydrolases/genetics/*metabolism ; }, abstract = {Pseudomonas aeruginosa is a leading cause of life-threatening nosocomial infections. Many virulence factors produced by P. aeruginosa are controlled by the cell-to-cell communication process called quorum sensing (QS). QS depends on the synthesis, release, and groupwide response to extracellular signaling molecules called autoinducers. P. aeruginosa possesses two canonical LuxI/R-type QS systems, LasI/R and RhlI/R, that produce and detect 3OC12-homoserine lactone and C4-homoserine lactone, respectively. Previously, we discovered that RhlR regulates both RhlI-dependent and RhlI-independent regulons, and we proposed that an alternative ligand functions together with RhlR to control the target genes in the absence of RhlI. Here, we report the identification of an enzyme, PqsE, which is the alternative-ligand synthase. Using biofilm analyses, reporter assays, site-directed mutagenesis, protein biochemistry, and animal infection studies, we show that the PqsE-produced alternative ligand is the key autoinducer that promotes virulence gene expression. Thus, PqsE can be targeted for therapeutic intervention. Furthermore, this work shows that PqsE and RhlR function as a QS-autoinducer synthase-receptor pair that drives group behaviors in P. aeruginosa.}, } @article {pmid30224495, year = {2018}, author = {Hayakawa, H and Motoyama, K and Sobue, F and Ito, T and Kawaide, H and Yoshimura, T and Hemmi, H}, title = {Modified mevalonate pathway of the archaeon Aeropyrum pernix proceeds via trans-anhydromevalonate 5-phosphate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10034-10039}, pmid = {30224495}, issn = {1091-6490}, mesh = {*Aconitate Hydratase/genetics/metabolism ; *Aeropyrum/genetics/metabolism ; *Archaeal Proteins/genetics/metabolism ; *Carboxy-Lyases/genetics/metabolism ; Mevalonic Acid/*metabolism ; Terpenes/*metabolism ; }, abstract = {The modified mevalonate pathway is believed to be the upstream biosynthetic route for isoprenoids in general archaea. The partially identified pathway has been proposed to explain a mystery surrounding the lack of phosphomevalonate kinase and diphosphomevalonate decarboxylase by the discovery of a conserved enzyme, isopentenyl phosphate kinase. Phosphomevalonate decarboxylase was considered to be the missing link that would fill the vacancy in the pathway between mevalonate 5-phosphate and isopentenyl phosphate. This enzyme was recently discovered from haloarchaea and certain Chroloflexi bacteria, but their enzymes are close homologs of diphosphomevalonate decarboxylase, which are absent in most archaea. In this study, we used comparative genomic analysis to find two enzymes from a hyperthermophilic archaeon, Aeropyrum pernix, that can replace phosphomevalonate decarboxylase. One enzyme, which has been annotated as putative aconitase, catalyzes the dehydration of mevalonate 5-phosphate to form a previously unknown intermediate, trans-anhydromevalonate 5-phosphate. Then, another enzyme belonging to the UbiD-decarboxylase family, which likely requires a UbiX-like partner, converts the intermediate into isopentenyl phosphate. Their activities were confirmed by in vitro assay with recombinant enzymes and were also detected in cell-free extract from A. pernix These data distinguish the modified mevalonate pathway of A. pernix and likely, of the majority of archaea from all known mevalonate pathways, such as the eukaryote-type classical pathway, the haloarchaea-type modified pathway, and another modified pathway recently discovered from Thermoplasma acidophilum.}, } @article {pmid30224494, year = {2018}, author = {Benton, DJ and Nans, A and Calder, LJ and Turner, J and Neu, U and Lin, YP and Ketelaars, E and Kallewaard, NL and Corti, D and Lanzavecchia, A and Gamblin, SJ and Rosenthal, PB and Skehel, JJ}, title = {Influenza hemagglutinin membrane anchor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10112-10117}, pmid = {30224494}, issn = {1091-6490}, support = {FC001078//Cancer Research UK/United Kingdom ; FC001143//Cancer Research UK/United Kingdom ; FC001078//Medical Research Council/International ; FC001078//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; FC001143//Wellcome Trust/United Kingdom ; FC001143//Medical Research Council/United Kingdom ; }, mesh = {Antibodies, Viral/chemistry ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry ; Immunoglobulin Fab Fragments/chemistry ; Influenza A Virus, H1N1 Subtype/*chemistry ; Micelles ; Protein Domains ; Protein Structure, Secondary ; }, abstract = {Viruses with membranes fuse them with cellular membranes, to transfer their genomes into cells at the beginning of infection. For Influenza virus, the membrane glycoprotein involved in fusion is the hemagglutinin (HA), the 3D structure of which is known from X-ray crystallographic studies. The soluble ectodomain fragments used in these studies lacked the "membrane anchor" portion of the molecule. Since this region has a role in membrane fusion, we have determined its structure by analyzing the intact, full-length molecule in a detergent micelle, using cryo-EM. We have also compared the structures of full-length HA-detergent micelles with full-length HA-Fab complex detergent micelles, to describe an infectivity-neutralizing monoclonal Fab that binds near the ectodomain membrane anchor junction. We determine a high-resolution HA structure which compares favorably in detail with the structure of the ectodomain seen by X-ray crystallography; we detect, clearly, all five carbohydrate side chains of HA; and we find that the ectodomain is joined to the membrane anchor by flexible, eight-residue-long, linkers. The linkers extend into the detergent micelle to join a central triple-helical structure that is a major component of the membrane anchor.}, } @article {pmid30224493, year = {2018}, author = {Rash, BG and Micali, N and Huttner, AJ and Morozov, YM and Horvath, TL and Rakic, P}, title = {Metabolic regulation and glucose sensitivity of cortical radial glial cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10142-10147}, pmid = {30224493}, issn = {1091-6490}, support = {P30 DK045735/DK/NIDDK NIH HHS/United States ; R01 DK111178/DK/NIDDK NIH HHS/United States ; R01 EY002593/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Calcium Signaling ; Cerebral Cortex/*embryology/pathology ; Diabetes, Gestational/genetics/*metabolism/pathology ; Female ; Glucose/*metabolism ; Hyperglycemia/*embryology/genetics/pathology ; Mice ; Mice, Transgenic ; Mitochondria/genetics/metabolism/pathology ; *Neurogenesis ; Neuroglia/*metabolism/pathology ; Pregnancy ; }, abstract = {The primary stem cells of the cerebral cortex are the radial glial cells (RGCs), and disturbances in their operation lead to myriad brain disorders in all mammals from mice to humans. Here, we found in mice that maternal gestational obesity and hyperglycemia can impair the maturation of RGC fibers and delay cortical neurogenesis. To investigate potential mechanisms, we used optogenetic live-imaging approaches in embryonic cortical slices. We found that Ca2+ signaling regulates mitochondrial transport and is crucial for metabolic support in RGC fibers. Cyclic intracellular Ca2+ discharge from localized RGC fiber segments detains passing mitochondria and ensures their proper distribution and enrichment at specific sites such as endfeet. Impairment of mitochondrial function caused an acute loss of Ca2+ signaling, while hyperglycemia decreased Ca2+ activity and impaired mitochondrial transport, leading to degradation of the RGC scaffold. Our findings uncover a physiological mechanism indicating pathways by which gestational metabolic disturbances can interfere with brain development.}, } @article {pmid30224492, year = {2018}, author = {Wei, Q and Krolewski, DM and Moore, S and Kumar, V and Li, F and Martin, B and Tomer, R and Murphy, GG and Deisseroth, K and Watson, SJ and Akil, H}, title = {Uneven balance of power between hypothalamic peptidergic neurons in the control of feeding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9489-E9498}, pmid = {30224492}, issn = {1091-6490}, support = {R01 MH104261/MH/NIMH NIH HHS/United States ; }, mesh = {Agouti Signaling Protein/*biosynthesis/genetics ; Animals ; Arcuate Nucleus of Hypothalamus/cytology/*metabolism ; Feeding Behavior/*physiology/psychology ; Mice ; Mice, Transgenic ; Neurons/cytology/*metabolism ; Neuropeptide Y/*biosynthesis/genetics ; Pro-Opiomelanocortin/*biosynthesis/genetics ; Signal Transduction/*physiology ; }, abstract = {Two classes of peptide-producing neurons in the arcuate nucleus (Arc) of the hypothalamus are known to exert opposing actions on feeding: the anorexigenic neurons that express proopiomelanocortin (POMC) and the orexigenic neurons that express agouti-related protein (AgRP) and neuropeptide Y (NPY). These neurons are thought to arise from a common embryonic progenitor, but our anatomical and functional understanding of the interplay of these two peptidergic systems that contribute to the control of feeding remains incomplete. The present study uses a combination of optogenetic stimulation with viral and transgenic approaches, coupled with neural activity mapping and brain transparency visualization to demonstrate the following: (i) selective activation of Arc POMC neurons inhibits food consumption rapidly in unsated animals; (ii) activation of Arc neurons arising from POMC-expressing progenitors, including POMC and a subset of AgRP neurons, triggers robust feeding behavior, even in the face of satiety signals from POMC neurons; (iii) the opposing effects on food intake are associated with distinct neuronal projection and activation patterns of adult hypothalamic POMC neurons versus Arc neurons derived from POMC-expressing lineages; and (iv) the increased food intake following the activation of orexigenic neurons derived from POMC-expressing progenitors engages an extensive neural network that involves the endogenous opioid system. Together, these findings shed further light on the dynamic balance between two peptidergic systems in the moment-to-moment regulation of feeding behavior.}, } @article {pmid30224491, year = {2018}, author = {Jachimowicz, JM and Wihler, A and Bailey, ER and Galinsky, AD}, title = {Why grit requires perseverance and passion to positively predict performance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9980-9985}, pmid = {30224491}, issn = {1091-6490}, abstract = {Prior studies linking grit-defined as perseverance and passion for long-term goals-to performance are beset by contradictory evidence. As a result, commentators have increasingly declared that grit has limited effects. We propose that this inconsistent evidence has occurred because prior research has emphasized perseverance and ignored, both theoretically and empirically, the critical role of passion, which we define as a strong feeling toward a personally important value/preference that motivates intentions and behaviors to express that value/preference. We suggest that combining the grit scale-which only captures perseverance-with a measure that assesses whether individuals attain desired levels of passion will predict performance. We first metaanalyzed 127 studies (n = 45,485) that used the grit scale and assessed performance, and found that effect sizes are larger in studies where participants were more passionate for the performance domain. Second, in a survey of employees matched to supervisor-rated job performance (n = 422), we found that the combination of perseverance, measured through the grit scale, and passion attainment, measured through a new scale, predicted higher performance. A final study measured perseverance and passion attainment in a sample of students (n = 248) and linked these to their grade-point average (GPA), finding that the combination of perseverance and passion attainment predicted higher GPAs in part through increased immersion. The present results help resolve the mixed evidence of grit's relationship with performance by highlighting the important role that passion plays in predicting performance. By adequately measuring both perseverance and passion, the present research uncovers grit's true predictive power.}, } @article {pmid30224490, year = {2018}, author = {}, title = {Correction for Loyer et al., Drosophila E-cadherin is required for the maintenance of ring canals anchoring to mechanically withstand tissue growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9260}, doi = {10.1073/pnas.1814899115}, pmid = {30224490}, issn = {1091-6490}, } @article {pmid30224489, year = {2018}, author = {Wang, Q and Jana, B and Diehl, MR and Cheung, MS and Kolomeisky, AB and Onuchic, JN}, title = {Molecular mechanisms of the interhead coordination by interhead tension in cytoplasmic dyneins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10052-10057}, pmid = {30224489}, issn = {1091-6490}, mesh = {Animals ; Cytoplasm/*chemistry/metabolism ; Dyneins/*chemistry/metabolism ; Humans ; *Models, Chemical ; *Models, Molecular ; }, abstract = {Cytoplasmic dyneins play a major role in retrograde cellular transport by moving vesicles and organelles along microtubule filaments. Dyneins are multidomain motor proteins with two heads that coordinate their motion via their interhead tension. Compared with the leading head, the trailing head has a higher detachment rate from microtubules, facilitating the movement. However, the molecular mechanism of such coordination is unknown. To elucidate this mechanism, we performed molecular dynamics simulations on a cytoplasmic dynein with a structure-based coarse-grained model that probes the effect of the interhead tension on the structure. The tension creates a torque that influences the head rotating about its stalk. The conformation of the stalk switches from the α registry to the β registry during the rotation, weakening the binding affinity to microtubules. The directions of the tension and the torque of the leading head are opposite to those of the trailing head, breaking the structural symmetry between the heads. The leading head transitions less often to the β registry than the trailing head. The former thus has a greater binding affinity to the microtubule than the latter. We measured the moment arm of the torque from a dynein structure in the simulations to develop a phenomenological model that captures the influence of the head rotating about its stalk on the differential detachment rates of the two heads. Our study provides a consistent molecular picture for interhead coordination via interhead tension.}, } @article {pmid30224488, year = {2018}, author = {Young, GR and Yap, MW and Michaux, JR and Steppan, SJ and Stoye, JP}, title = {Evolutionary journey of the retroviral restriction gene Fv1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10130-10135}, pmid = {30224488}, issn = {1091-6490}, support = {FC001162//Cancer Research UK/United Kingdom ; FC001162//Medical Research Council/United Kingdom ; FC001162//Wellcome Trust/United Kingdom ; K23 MH001948/MH/NIMH NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Evolution, Molecular ; Mice ; Murinae ; Proteins/*genetics ; }, abstract = {Both exogenous and endogenous retroviruses have long been studied in mice, and some of the earliest mouse studies focused on the heritability of genetic factors influencing permissivity and resistance to infection. The prototypic retroviral restriction factor, Fv1, is now understood to exhibit a degree of control across multiple retroviral genera and is highly diverse within Mus To better understand the age and evolutionary history of Fv1, a comprehensive survey of the Muroidea was conducted, allowing the progenitor integration to be dated to ∼45 million years. Intact coding potential is visible beyond Mus, and sequence analysis reveals strong signatures of positive selection also within field mice, ApodemusFv1's survival for such a period implies a recurring and shifting retroviral burden imparting the necessary selective pressures-an influence likely also common to analogous factors. Regions of Fv1 adapt cooperatively, highlighting its preference for repeated structures and suggesting that this functionally constrained aspect of the retroviral capsid lattice presents a common target in the evolution of intrinsic immunity.}, } @article {pmid30224487, year = {2018}, author = {Freeman, J and Baggio, JA and Robinson, E and Byers, DA and Gayo, E and Finley, JB and Meyer, JA and Kelly, RL and Anderies, JM}, title = {Synchronization of energy consumption by human societies throughout the Holocene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9962-9967}, pmid = {30224487}, issn = {1091-6490}, mesh = {*Archaeology ; *Ecosystem ; *Fossil Fuels ; History, Ancient ; Humans ; *Social Change ; Socioeconomic Factors ; Sociology ; }, abstract = {We conduct a global comparison of the consumption of energy by human populations throughout the Holocene and statistically quantify coincident changes in the consumption of energy over space and time-an ecological phenomenon known as synchrony. When populations synchronize, adverse changes in ecosystems and social systems may cascade from society to society. Thus, to develop policies that favor the sustained use of resources, we must understand the processes that cause the synchrony of human populations. To date, it is not clear whether human societies display long-term synchrony or, if they do, the potential causes. Our analysis begins to fill this knowledge gap by quantifying the long-term synchrony of human societies, and we hypothesize that the synchrony of human populations results from (i) the creation of social ties that couple populations over smaller scales and (ii) much larger scale, globally convergent trajectories of cultural evolution toward more energy-consuming political economies with higher carrying capacities. Our results suggest that the process of globalization is a natural consequence of evolutionary trajectories that increase the carrying capacities of human societies.}, } @article {pmid30224486, year = {2018}, author = {Virzì, AR and Gentile, A and Benvenuti, S and Comoglio, PM}, title = {Reviving oncogenic addiction to MET bypassed by BRAF (G469A) mutation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10058-10063}, pmid = {30224486}, issn = {1091-6490}, mesh = {A549 Cells ; Amino Acid Substitution ; Animals ; Humans ; Mice, Inbred NOD ; Mice, SCID ; *Mutation, Missense ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Protein Phosphatase 2/genetics/metabolism ; *Proto-Oncogene Proteins B-raf/genetics/metabolism ; *Proto-Oncogene Proteins c-met/antagonists & inhibitors/genetics/metabolism ; Pyrazoles/*pharmacology ; Pyridazines/*pharmacology ; Xenograft Model Antitumor Assays ; }, abstract = {Cancer clonal evolution is based on accrual of driving genetic alterations that are expected to cooperate and progressively increase malignancy. Little is known on whether any genetic alteration can hinder the oncogenic function of a coexisting alteration, so that therapeutic targeting of the one can, paradoxically, revive the function of the other. We report the case of a driver oncogene (MET) that is not only bypassed, but also disabled by the mutation of a downstream transducer (BRAF), and reignited by inhibition of the latter. In a metastasis originated from a cancer of unknown primary (CUP), the MET oncogene was amplified eightfold, but unexpectedly, the kinase was dephosphorylated and inactive. As result, specific drugs targeting MET (JNJ-38877605) failed to inhibit growth of xenografts derived from the patient. In addition to MET amplification, the patient harbored, as sole proliferative driver, a mutation hyperactivating BRAF (G469A). Surprisingly, specific blockade of the BRAF pathway was equally ineffective, and it was accompanied by rephosphorylation of the amplified MET oncoprotein and by revived addiction to MET. Mechanistically, MET inactivation in the context of the BRAF-activating mutation is driven through a negative feedback loop involving inactivation of PP2A phosphatase, which in turn leads to phosphorylation on MET inhibitory Ser985. Disruption of this feedback loop allows PP2A reactivation, removing the inhibitory phosphorylation from Ser985 and thereby unleashing MET kinase activity. Evidence is provided for a mechanism of therapeutic resistance to single-oncoprotein targeting, based on reactivation of a genetic alteration functionally dormant in targeted cancer cells.}, } @article {pmid30224485, year = {2018}, author = {Deng, P and Zhou, Y and Jiang, J and Li, H and Tian, W and Cao, Y and Qin, Y and Kim, J and Roeder, RG and Patel, DJ and Wang, Z}, title = {Transcriptional elongation factor Paf1 core complex adopts a spirally wrapped solenoidal topology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9998-10003}, pmid = {30224485}, issn = {1091-6490}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA129325/CA/NCI NIH HHS/United States ; R01 DK071900/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Cell Cycle Proteins/*chemistry ; DNA, Single-Stranded/chemistry ; Multiprotein Complexes/*chemistry ; Nuclear Proteins/*chemistry ; Protein Domains ; Protein Structure, Quaternary ; Saccharomyces cerevisiae/*chemistry ; Saccharomyces cerevisiae Proteins/*chemistry ; Transcriptional Elongation Factors/*chemistry ; }, abstract = {The polymerase-associated factor 1 (Paf1) complex is a general transcription elongation factor of RNA polymerase II, which is composed of five core subunits, Paf1, Ctr9, Cdc73, Leo1, and Rtf1, and functions as a diverse platform that broadly affects gene expression genome-wide. In this study, we solved the 2.9-Å crystal structure of the core region composed of the Ctr9-Paf1-Cdc73 ternary complex from a thermophilic fungi, which provides a structural perspective of the molecular details of the organization and interactions involving the Paf1 subunits in the core complex. We find that Ctr9 is composed of 21 tetratricopeptide repeat (TPR) motifs that wrap three circular turns in a right-handed superhelical manner around the N-terminal region of an elongated single-polypeptide-chain scaffold of Paf1. The Cdc73 fragment is positioned within the surface groove of Ctr9, where it contacts mainly with Ctr9 and minimally with Paf1. We also identified that the Paf1 complex preferentially binds single-strand-containing DNAs. Our work provides structural insights into the overall architecture of the Paf1 complex and paves the road forward for understanding the molecular mechanisms of the Paf1 complex in transcriptional regulation.}, } @article {pmid30224484, year = {2018}, author = {Zhu, C and Yan, Q and Weng, C and Hou, X and Mao, H and Liu, D and Feng, X and Guang, S}, title = {Erroneous ribosomal RNAs promote the generation of antisense ribosomal siRNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10082-10087}, pmid = {30224484}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {*Gene Silencing ; Humans ; *Methyltransferases/genetics/metabolism ; *Nuclear Proteins/genetics/metabolism ; *RNA, Ribosomal/genetics/metabolism ; *RNA, Ribosomal, 18S/genetics/metabolism ; *RNA, Small Interfering/genetics/metabolism ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {Ribosome biogenesis is a multistep process, during which mistakes can occur at any step of pre-rRNA processing, modification, and ribosome assembly. Misprocessed rRNAs are usually detected and degraded by surveillance machineries. Recently, we identified a class of antisense ribosomal siRNAs (risiRNAs) that down-regulate pre-rRNAs through the nuclear RNAi pathway. To further understand the biological roles of risiRNAs, we conducted both forward and reverse genetic screens to search for more suppressor of siRNA (susi) mutants. We isolated a number of genes that are broadly conserved from yeast to humans and are involved in pre-rRNA modification and processing. Among them, SUSI-2(ceRRP8) is homologous to human RRP8 and engages in m1A methylation of the 26S rRNA. C27F2.4(ceBUD23) is an m7G-methyltransferase of the 18S rRNA. E02H1.1(ceDIMT1L) is a predicted m6(2)Am6(2)A-methyltransferase of the 18S rRNA. Mutation of these genes led to a deficiency in modification of rRNAs and elicited accumulation of risiRNAs, which further triggered the cytoplasmic-to-nuclear and cytoplasmic-to-nucleolar translocations of the Argonaute protein NRDE-3. The rRNA processing deficiency also resulted in accumulation of risiRNAs. We also isolated SUSI-3(RIOK-1), which is similar to human RIOK1, that cleaves the 20S rRNA to 18S. We further utilized RNAi and CRISPR-Cas9 technologies to perform candidate-based reverse genetic screens and identified additional pre-rRNA processing factors that suppressed risiRNA production. Therefore, we concluded that erroneous rRNAs can trigger risiRNA generation and subsequently, turn on the nuclear RNAi-mediated gene silencing pathway to inhibit pre-rRNA expression, which may provide a quality control mechanism to maintain homeostasis of rRNAs.}, } @article {pmid30224483, year = {2018}, author = {Ramachandran, K and Di Luccio, T and Ailianou, A and Kossuth, MB and Oberhauser, JP and Kornfield, JA}, title = {Crimping-induced structural gradients explain the lasting strength of poly l-lactide bioresorbable vascular scaffolds during hydrolysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10239-10244}, pmid = {30224483}, issn = {1091-6490}, support = {F31 HL137308/HL/NHLBI NIH HHS/United States ; }, mesh = {*Absorbable Implants ; Hydrolysis ; Materials Testing ; Microscopy, Electron, Scanning ; Microtomy ; Molecular Weight ; Polyesters/*chemistry ; Tissue Scaffolds/*chemistry ; X-Ray Diffraction ; }, abstract = {Biodegradable polymers open the way to treatment of heart disease using transient implants (bioresorbable vascular scaffolds, BVSs) that overcome the most serious complication associated with permanent metal stents-late stent thrombosis. Here, we address the long-standing paradox that the clinically approved BVS maintains its radial strength even after 9 mo of hydrolysis, which induces a ∼40% decrease in the poly l-lactide molecular weight (Mn). X-ray microdiffraction evidence of nonuniform hydrolysis in the scaffold reveals that regions subjected to tensile stress during crimping develop a microstructure that provides strength and resists hydrolysis. These beneficial morphological changes occur where they are needed most-where stress is localized when a radial load is placed on the scaffold. We hypothesize that the observed decrease in Mn reflects the majority of the material, which is undeformed during crimping. Thus, the global measures of degradation may be decoupled from the localized, degradation-resistant regions that confer the ability to support the artery for the first several months after implantation.}, } @article {pmid30224482, year = {2018}, author = {Chernyshova, IV and Somasundaran, P and Ponnurangam, S}, title = {On the origin of the elusive first intermediate of CO2 electroreduction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9261-E9270}, pmid = {30224482}, issn = {1091-6490}, abstract = {We resolve the long-standing controversy about the first step of the CO2 electroreduction to fuels in aqueous electrolytes by providing direct spectroscopic evidence that the first intermediate of the CO2 conversion to formate on copper is a carboxylate anion *CO2- coordinated to the surface through one of its C-O bonds. We identify this intermediate and gain insight into its formation, its chemical and electronic properties, as well as its dependence on the electrode potential by taking advantage of a cutting-edge methodology that includes operando surface-enhanced Raman scattering (SERS) empowered by isotope exchange and electrochemical Stark effects, reaction kinetics (Tafel) analysis, and density functional theory (DFT) simulations. The SERS spectra are measured on an operating Cu surface. These results advance the mechanistic understanding of CO2 electroreduction and its selectivity to carbon monoxide and formate.}, } @article {pmid30224481, year = {2018}, author = {Cheng, X and Jobin-Robitaille, O and Billon, P and Buisson, R and Niu, H and Lacoste, N and Abshiru, N and Côté, V and Thibault, P and Kron, SJ and Sung, P and Brandl, CJ and Masson, JY and Côté, J}, title = {Phospho-dependent recruitment of the yeast NuA4 acetyltransferase complex by MRX at DNA breaks regulates RPA dynamics during resection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10028-10033}, pmid = {30224481}, issn = {1091-6490}, support = {R00 ES021441/ES/NIEHS NIH HHS/United States ; R01 GM060443/GM/NIGMS NIH HHS/United States ; MOP-14308//Canadian Institutes of Health Research/International ; FDN-143314//Canadian Institutes of Health Research/International ; }, mesh = {Acetylation ; *DNA Breaks, Double-Stranded ; *DNA, Fungal/chemistry/metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Endodeoxyribonucleases/chemistry/metabolism ; Exodeoxyribonucleases/chemistry/metabolism ; *Histone Acetyltransferases/chemistry/metabolism ; *Saccharomyces cerevisiae Proteins/chemistry/metabolism ; Tumor Suppressor p53-Binding Protein 1/chemistry/metabolism ; }, abstract = {The KAT5 (Tip60/Esa1) histone acetyltransferase is part of NuA4, a large multifunctional complex highly conserved from yeast to mammals that targets lysines on H4 and H2A (X/Z) tails for acetylation. It is essential for cell viability, being a key regulator of gene expression, cell proliferation, and stem cell renewal and an important factor for genome stability. The NuA4 complex is directly recruited near DNA double-strand breaks (DSBs) to facilitate repair, in part through local chromatin modification and interplay with 53BP1 during the DNA damage response. While NuA4 is detected early after appearance of the lesion, its precise mechanism of recruitment remains to be defined. Here, we report a stepwise recruitment of yeast NuA4 to DSBs first by a DNA damage-induced phosphorylation-dependent interaction with the Xrs2 subunit of the Mre11-Rad50-Xrs2 (MRX) complex bound to DNA ends. This is followed by a DNA resection-dependent spreading of NuA4 on each side of the break along with the ssDNA-binding replication protein A (RPA). Finally, we show that NuA4 can acetylate RPA and regulate the dynamics of its binding to DNA, hence targeting locally both histone and nonhistone proteins for lysine acetylation to coordinate repair.}, } @article {pmid30224480, year = {2018}, author = {Takae, K and Tanaka, H}, title = {Self-organization into ferroelectric and antiferroelectric crystals via the interplay between particle shape and dipolar interaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9917-9922}, pmid = {30224480}, issn = {1091-6490}, abstract = {Ferroelectricity and antiferroelectricity are widely seen in various types of condensed matter and are of technological significance not only due to their electrical switchability but also due to intriguing cross-coupling effects such as electro-mechanical and electro-caloric effects. The control of the two types of dipolar order has practically been made by changing the ionic radius of a constituent atom or externally applying strain for inorganic crystals and by changing the shape of a molecule for organic crystals. However, the basic physical principle behind such controllability involving crystal-lattice organization is still unknown. On the basis of a physical picture that a competition of dipolar order with another type of order is essential to understand this phenomenon, here we develop a simple model system composed of spheroid-like particles with a permanent dipole, which may capture an essence of this important structural transition in organic systems. In this model, we reveal that energetic frustration between the two types of anisotropic interactions, dipolar and steric interactions, is a key to control not only the phase transition but also the coupling between polarization and strain. Our finding provides a fundamental physical principle for self-organization to a crystal with desired dipolar order and realization of large electro-mechanical effects.}, } @article {pmid30224479, year = {2018}, author = {Li, BB and Qian, C and Gameiro, PA and Liu, CC and Jiang, T and Roberts, TM and Struhl, K and Zhao, JJ}, title = {Targeted profiling of RNA translation reveals mTOR-4EBP1/2-independent translation regulation of mRNAs encoding ribosomal proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9325-E9332}, pmid = {30224479}, issn = {1091-6490}, support = {R01 CA187918/CA/NCI NIH HHS/United States ; P50 CA168504/CA/NCI NIH HHS/United States ; R35 CA210057/CA/NCI NIH HHS/United States ; R01 CA107486/CA/NCI NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Carrier Proteins/genetics/*metabolism ; Cell Line, Transformed ; Cell Line, Tumor ; Eukaryotic Initiation Factor-2/genetics/metabolism ; Humans ; Multiprotein Complexes/genetics/*metabolism ; *Protein Biosynthesis ; Protein-Serine-Threonine Kinases/genetics/metabolism ; RNA, Messenger/genetics/*metabolism ; RNA-Binding Proteins/genetics/*metabolism ; Ribosomal Proteins/*biosynthesis/genetics ; *Signal Transduction ; TOR Serine-Threonine Kinases/genetics/*metabolism ; }, abstract = {The PI3K-Akt-mTOR signaling pathway is a master regulator of RNA translation. Pharmacological inhibition of this pathway preferentially and coordinately suppresses, in a 4EBP1/2-dependent manner, translation of mRNAs encoding ribosomal proteins. However, it is unclear whether mechanistic target of rapamycin (mTOR)-4EBP1/2 is the exclusive translation regulator of this group of genes, and furthermore, systematic searches for novel translation modulators have been immensely challenging because of difficulties in scaling existing RNA translation profiling assays. Here, we developed a rapid and highly scalable approach for gene-specific quantitation of RNA translation, termed Targeted Profiling of RNA Translation (TPRT). We applied this technique in a chemical screen for translation modulators, and identified numerous preclinical and clinical therapeutic compounds, with diverse nominal targets, that preferentially suppress translation of ribosomal proteins. Surprisingly, some of these compounds act in a manner that bypasses canonical regulation by mTOR-4EBP1/2. Instead, these compounds exert their translation effects in a manner that is dependent on GCN2-eIF2α, a central signaling axis within the integrated stress response. Furthermore, we were also able to identify metabolic perturbations that also suppress ribosomal protein translation in an mTOR-independent manner. Together, we describe a translation assay that is directly applicable to large-scale RNA translation studies, and that enabled us to identify a noncanonical, mTOR-independent mode for translation regulation of ribosomal proteins.}, } @article {pmid30224478, year = {2018}, author = {Kropp, HM and Dürr, SL and Peter, C and Diederichs, K and Marx, A}, title = {Snapshots of a modified nucleotide moving through the confines of a DNA polymerase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9992-9997}, pmid = {30224478}, issn = {1091-6490}, support = {339834//European Research Council/International ; }, mesh = {Bacterial Proteins/*chemistry ; Crystallography, X-Ray ; DNA/*chemistry ; DNA Polymerase I/*chemistry ; *Models, Molecular ; Taq Polymerase/*chemistry ; Thermus/*enzymology ; }, abstract = {DNA polymerases have evolved to process the four canonical nucleotides accurately. Nevertheless, these enzymes are also known to process modified nucleotides, which is the key to numerous core biotechnology applications. Processing of modified nucleotides includes incorporation of the modified nucleotide and postincorporation elongation to proceed with the synthesis of the nascent DNA strand. The structural basis for postincorporation elongation is currently unknown. We addressed this issue and successfully crystallized KlenTaq DNA polymerase in six closed ternary complexes containing the enzyme, the modified DNA substrate, and the incoming nucleotide. Each structure shows a high-resolution snapshot of the elongation of a modified primer, where the modification "moves" from the 3'-primer terminus upstream to the sixth nucleotide in the primer strand. Combining these data with quantum mechanics/molecular mechanics calculations and biochemical studies elucidates how the enzyme and the modified substrate mutually modulate their conformations without compromising the enzyme's activity significantly. The study highlights the plasticity of the system as origin of the broad substrate properties of DNA polymerases and facilitates the design of improved systems.}, } @article {pmid30224477, year = {2018}, author = {Gennaro, VJ and Stanek, TJ and Peck, AR and Sun, Y and Wang, F and Qie, S and Knudsen, KE and Rui, H and Butt, T and Diehl, JA and McMahon, SB}, title = {Control of CCND1 ubiquitylation by the catalytic SAGA subunit USP22 is essential for cell cycle progression through G1 in cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9298-E9307}, pmid = {30224477}, issn = {1091-6490}, support = {R01 CA182569/CA/NCI NIH HHS/United States ; }, mesh = {Colorectal Neoplasms/genetics/*metabolism/pathology ; Cyclin D1/genetics/*metabolism ; *Epigenesis, Genetic ; *G1 Phase ; *Gene Expression Regulation, Neoplastic ; Humans ; Lung Neoplasms/genetics/*metabolism/pathology ; MCF-7 Cells ; Protein Stability ; *Proteolysis ; Thiolester Hydrolases/genetics/*metabolism ; *Ubiquitination ; }, abstract = {Overexpression of the deubiquitylase ubiquitin-specific peptidase 22 (USP22) is a marker of aggressive cancer phenotypes like metastasis, therapy resistance, and poor survival. Functionally, this overexpression of USP22 actively contributes to tumorigenesis, as USP22 depletion blocks cancer cell cycle progression in vitro, and inhibits tumor progression in animal models of lung, breast, bladder, ovarian, and liver cancer, among others. Current models suggest that USP22 mediates these biological effects via its role in epigenetic regulation as a subunit of the Spt-Ada-Gcn5-acetyltransferase (SAGA) transcriptional cofactor complex. Challenging the dogma, we report here a nontranscriptional role for USP22 via a direct effect on the core cell cycle machinery: that is, the deubiquitylation of the G1 cyclin D1 (CCND1). Deubiquitylation by USP22 protects CCND1 from proteasome-mediated degradation and occurs separately from the canonical phosphorylation/ubiquitylation mechanism previously shown to regulate CCND1 stability. We demonstrate that control of CCND1 is a key mechanism by which USP22 mediates its known role in cell cycle progression. Finally, USP22 and CCND1 levels correlate in patient lung and colorectal cancer samples and our preclinical studies indicate that targeting USP22 in combination with CDK inhibitors may offer an approach for treating cancer patients whose tumors exhibit elevated CCND1.}, } @article {pmid30224476, year = {2018}, author = {}, title = {Correction for Sharp et al., Psychological targeting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9257}, doi = {10.1073/pnas.1814739115}, pmid = {30224476}, issn = {1091-6490}, } @article {pmid30224475, year = {2018}, author = {Lerma-Usabiaga, G and Carreiras, M and Paz-Alonso, PM}, title = {Converging evidence for functional and structural segregation within the left ventral occipitotemporal cortex in reading.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9981-E9990}, pmid = {30224475}, issn = {1091-6490}, mesh = {Adult ; Brain Mapping/*methods ; Cerebral Cortex/*physiology ; Female ; Functional Laterality/*physiology ; Humans ; Image Processing, Computer-Assisted ; Magnetic Resonance Imaging ; Male ; Mental Processes/*physiology ; Neural Pathways ; Neuropsychological Tests ; Occipital Lobe/*physiology ; Psychomotor Performance ; *Reading ; Temporal Lobe/*physiology ; Young Adult ; }, abstract = {The ventral occipitotemporal cortex (vOTC) is crucial for recognizing visual patterns, and previous evidence suggests that there may be different subregions within the vOTC involved in the rapid identification of word forms. Here, we characterize vOTC reading circuitry using a multimodal approach combining functional, structural, and quantitative MRI and behavioral data. Two main word-responsive vOTC areas emerged: a posterior area involved in visual feature extraction, structurally connected to the intraparietal sulcus via the vertical occipital fasciculus; and an anterior area involved in integrating information with other regions of the language network, structurally connected to the angular gyrus via the posterior arcuate fasciculus. Furthermore, functional activation in these vOTC regions predicted reading behavior outside of the scanner. Differences in the microarchitectonic properties of gray-matter cells in these segregated areas were also observed, in line with earlier cytoarchitectonic evidence. These findings advance our understanding of the vOTC circuitry by linking functional responses to anatomical structure, revealing the pathways of distinct reading-related processes.}, } @article {pmid30224474, year = {2018}, author = {Fugère, V and Hendry, AP}, title = {Human influences on the strength of phenotypic selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10070-10075}, pmid = {30224474}, issn = {1091-6490}, mesh = {Humans ; *Models, Genetic ; *Phenotype ; *Selection, Genetic ; }, abstract = {Human activities are driving rapid phenotypic change in many species, with harvesting considered to be a particularly potent evolutionary force. We hypothesized that faster evolutionary change in human-disturbed populations could be caused by a strengthening of phenotypic selection, for example, if human disturbances trigger maladaptation and/or increase the opportunity for selection. We tested this hypothesis by synthesizing 1,366 phenotypic selection coefficients from 37 species exposed to various anthropogenic disturbances, including harvest. We used a paired design that only included studies measuring selection on the same traits in both human-disturbed and control (not obviously human-disturbed "natural") populations. Surprisingly, this meta-analysis did not reveal stronger selection in human-disturbed environments; in fact, we even found some evidence that human disturbances might slightly reduce selection strength. The only clear exceptions were two fisheries showing very strong harvest selection. On closer inspection, we discovered that many disturbances weakened selection by increasing absolute fitness and by decreasing the opportunity for selection-thus explaining what initially seemed a counterintuitive result. We discuss how human disturbances can sometimes weaken rather than strengthen selection, and why measuring the total effect of disturbances on selection is exceedingly difficult. Despite these challenges, documenting human influences on selection can reveal disturbances with particularly strong effects (e.g., fishing), and thus better inform the management of populations exposed to these disturbances.}, } @article {pmid30224473, year = {2018}, author = {}, title = {Correction for Schickinger et al., Tethered multifluorophore motion reveals equilibrium transition kinetics of single DNA double helices.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9259}, doi = {10.1073/pnas.1814449115}, pmid = {30224473}, issn = {1091-6490}, } @article {pmid30224472, year = {2018}, author = {Dhar, M and Lam, JN and Walser, T and Dubinett, SM and Rettig, MB and Di Carlo, D}, title = {Functional profiling of circulating tumor cells with an integrated vortex capture and single-cell protease activity assay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9986-9991}, pmid = {30224472}, issn = {1091-6490}, support = {R33 CA177456/CA/NCI NIH HHS/United States ; U01 CA214182/CA/NCI NIH HHS/United States ; }, mesh = {A549 Cells ; *Cell Separation/instrumentation/methods ; Collagenases/*metabolism ; Humans ; *Lab-On-A-Chip Devices ; *Microfluidic Analytical Techniques/instrumentation/methods ; Neoplasm Proteins/*metabolism ; Neoplastic Cells, Circulating/*metabolism/pathology ; }, abstract = {Tumor cells are hypothesized to use proteolytic enzymes to facilitate invasion. Whether circulating tumor cells (CTCs) secrete these enzymes to aid metastasis is unknown. A quantitative and high-throughput approach to assay CTC secretion is needed to address this question. We developed an integrated microfluidic system that concentrates rare cancer cells >100,000-fold from 1 mL of whole blood into ∼50,000 2-nL drops composed of assay reagents within 15 min. The system isolates CTCs by size, exchanges fluid around CTCs to remove contaminants, introduces a matrix metalloprotease (MMP) substrate, and encapsulates CTCs into microdroplets. We found CTCs from prostate cancer patients possessed above baseline levels of MMP activity (1.7- to 200-fold). Activity of CTCs was generally higher than leukocytes from the same patient (average CTC/leukocyte MMP activity ratio, 2.6 ± 1.5). Higher MMP activity of CTCs suggests active proteolytic processes that may facilitate invasion or immune evasion and be relevant phenotypic biomarkers enabling companion diagnostics for anti-MMP therapies.}, } @article {pmid30224471, year = {2018}, author = {Guiley, KZ and Iness, AN and Saini, S and Tripathi, S and Lipsick, JS and Litovchick, L and Rubin, SM}, title = {Structural mechanism of Myb-MuvB assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10016-10021}, pmid = {30224471}, issn = {1091-6490}, support = {R01 CA128836/CA/NCI NIH HHS/United States ; F31 CA206244/CA/NCI NIH HHS/United States ; R01 CA132685/CA/NCI NIH HHS/United States ; R01 GM124148/GM/NIGMS NIH HHS/United States ; R01 CA188571/CA/NCI NIH HHS/United States ; }, mesh = {*Cell Cycle ; *Cell Cycle Proteins/chemistry/metabolism ; Cell Line ; Crystallography, X-Ray ; Humans ; *Multiprotein Complexes/chemistry/metabolism ; *Neoplasm Proteins/chemistry/metabolism ; *Neoplasms/chemistry/metabolism ; *Nuclear Proteins/chemistry/metabolism ; Protein Domains ; *Trans-Activators/chemistry/metabolism ; *Tumor Suppressor Proteins/chemistry/metabolism ; }, abstract = {The MuvB transcriptional regulatory complex, which controls cell-cycle-dependent gene expression, cooperates with B-Myb to activate genes required for the G2 and M phases of the cell cycle. We have identified the domain in B-Myb that is essential for the assembly of the Myb-MuvB (MMB) complex. We determined a crystal structure that reveals how this B-Myb domain binds MuvB through the adaptor protein LIN52 and the scaffold protein LIN9. The structure and biochemical analysis provide an understanding of how oncogenic B-Myb is recruited to regulate genes required for cell-cycle progression, and the MMB interface presents a potential therapeutic target to inhibit cancer cell proliferation.}, } @article {pmid30224470, year = {2018}, author = {Gonzalez-Perez, V and Ben Johny, M and Xia, XM and Lingle, CJ}, title = {Regulatory γ1 subunits defy symmetry in functional modulation of BK channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9923-9928}, pmid = {30224470}, issn = {1091-6490}, support = {R35 GM118114/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Fluorescence Resonance Energy Transfer/methods ; Ion Channel Gating/*physiology ; Large-Conductance Calcium-Activated Potassium Channel alpha Subunits/genetics/*metabolism ; Mice ; Protein Subunits/genetics/*metabolism ; Xenopus laevis ; }, abstract = {Structural symmetry is a hallmark of homomeric ion channels. Nonobligatory regulatory proteins can also critically define the precise functional role of such channels. For instance, the pore-forming subunit of the large conductance voltage and calcium-activated potassium (BK, Slo1, or KCa1.1) channels encoded by a single KCa1.1 gene assembles in a fourfold symmetric fashion. Functional diversity arises from two families of regulatory subunits, β and γ, which help define the range of voltages over which BK channels in a given cell are activated, thereby defining physiological roles. A BK channel can contain zero to four β subunits per channel, with each β subunit incrementally influencing channel gating behavior, consistent with symmetry expectations. In contrast, a γ1 subunit (or single type of γ1 subunit complex) produces a functionally all-or-none effect, but the underlying stoichiometry of γ1 assembly and function remains unknown. Here we utilize two distinct and independent methods, a Forster resonance energy transfer-based optical approach and a functional reporter in single-channel recordings, to reveal that a BK channel can contain up to four γ1 subunits, but a single γ1 subunit suffices to induce the full gating shift. This requires that the asymmetric association of a single regulatory protein can act in a highly concerted fashion to allosterically influence conformational equilibria in an otherwise symmetric K+ channel.}, } @article {pmid30224469, year = {2018}, author = {}, title = {Correction for Lanaspa et al., High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9509}, doi = {10.1073/pnas.1815006115}, pmid = {30224469}, issn = {1091-6490}, } @article {pmid30224468, year = {2018}, author = {Bang, J and Lee, SY}, title = {Assimilation of formic acid and CO2 by engineered Escherichia coli equipped with reconstructed one-carbon assimilation pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9271-E9279}, pmid = {30224468}, issn = {1091-6490}, mesh = {*Bacterial Proteins/metabolism ; Carbon Dioxide/*metabolism ; *Escherichia coli/genetics/metabolism ; *Formate-Tetrahydrofolate Ligase/genetics/metabolism ; Formates/*metabolism ; Gene Knockdown Techniques ; Methylobacterium extorquens/enzymology/*genetics ; *Microorganisms, Genetically-Modified/genetics/metabolism ; }, abstract = {Gaseous one-carbon (C1) compounds or formic acid (FA) converted from CO2 can be an attractive raw material for bio-based chemicals. Here, we report the development of Escherichia coli strains assimilating FA and CO2 through the reconstructed tetrahydrofolate (THF) cycle and reverse glycine cleavage (gcv) pathway. The Methylobacterium extorquens formate-THF ligase, methenyl-THF cyclohydrolase, and methylene-THF dehydrogenase genes were expressed to allow FA assimilation. The gcv reaction was reversed by knocking out the repressor gene (gcvR) and overexpressing the gcvTHP genes. This engineered strain synthesized 96% and 86% of proteinogenic glycine and serine, respectively, from FA and CO2 in a glucose-containing medium. Native serine deaminase converted serine to pyruvate, showing 4.5% of pyruvate-forming flux comes from FA and CO2 The pyruvate-forming flux from FA and CO2 could be increased to 14.9% by knocking out gcvR, pflB, and serA, chromosomally expressing gcvTHP under trc, and overexpressing the reconstructed THF cycle, gcvTHP, and lpd genes in one vector. To reduce glucose usage required for energy and redox generation, the Candida boidinii formate dehydrogenase (Fdh) gene was expressed. The resulting strain showed specific glucose, FA, and CO2 consumption rates of 370.2, 145.6, and 14.9 mg⋅g dry cell weight (DCW)-1⋅h-1, respectively. The C1 assimilation pathway consumed 21.3 wt% of FA. Furthermore, cells sustained slight growth using only FA and CO2 after glucose depletion, suggesting that combined use of the C1 assimilation pathway and C. boidinii Fdh will be useful for eventually developing a strain capable of utilizing FA and CO2 without an additional carbon source such as glucose.}, } @article {pmid30224467, year = {2018}, author = {Rieckmann, A and Johnson, KA and Sperling, RA and Buckner, RL and Hedden, T}, title = {Dedifferentiation of caudate functional connectivity and striatal dopamine transporter density predict memory change in normal aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10160-10165}, pmid = {30224467}, issn = {1091-6490}, support = {R01 AG053509/AG/NIA NIH HHS/United States ; K24 AG035007/AG/NIA NIH HHS/United States ; P01 AG036694/AG/NIA NIH HHS/United States ; S10 RR019254/RR/NCRR NIH HHS/United States ; S10 RR019307/RR/NCRR NIH HHS/United States ; P50 AG005134/AG/NIA NIH HHS/United States ; R01 AG034556/AG/NIA NIH HHS/United States ; S10 RR023043/RR/NCRR NIH HHS/United States ; R01 AG054110/AG/NIA NIH HHS/United States ; K01 AG040197/AG/NIA NIH HHS/United States ; P41 EB015896/EB/NIBIB NIH HHS/United States ; S10 RR023401/RR/NCRR NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aging/*physiology ; *Cerebral Cortex/diagnostic imaging/physiology ; *Corpus Striatum/diagnostic imaging/physiology ; Dopamine Plasma Membrane Transport Proteins/*metabolism ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Memory/*physiology ; Middle Aged ; *Trigeminal Caudal Nucleus/diagnostic imaging/metabolism ; }, abstract = {Age-related changes in striatal function are potentially important for predicting declining memory performance over the adult life span. Here, we used fMRI to measure functional connectivity of caudate subfields with large-scale association networks and positron emission tomography to measure striatal dopamine transporter (DAT) density in 51 older adults (age 65-86 years) who received annual cognitive testing for up to 7 years (mean = 5.59, range 2-7 years). Analyses showed that cortical-caudate functional connectivity was less differentiated in older compared with younger adults (n = 63, age 18-32 years). Unlike in younger adults, the central lateral caudate was less strongly coupled with the frontal parietal control network in older adults. Older adults also showed less "decoupling" of the caudate from other networks, including areas of the default network (DN) and the hippocampal complex. Contrary to expectations, less decoupling between caudate and the DN was not associated with an age-related reduction of striatal DAT, suggesting that neurobiological changes in the cortex may drive dedifferentiation of cortical-caudate connectivity. Reduction of specificity in functional coupling between caudate and regions of the DN predicted memory decline over subsequent years at older ages. The age-related reduction in striatal DAT density also predicted memory decline, suggesting that a relation between striatal functions and memory decline in aging is multifaceted. Collectively, the study provides evidence highlighting the association of age-related differences in striatal function to memory decline in normal aging.}, } @article {pmid30224466, year = {2018}, author = {Zeng, X and Xia, Y and Tong, H}, title = {Jackknife approach to the estimation of mutual information.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9956-9961}, pmid = {30224466}, issn = {1091-6490}, abstract = {Quantifying the dependence between two random variables is a fundamental issue in data analysis, and thus many measures have been proposed. Recent studies have focused on the renowned mutual information (MI) [Reshef DN, et al. (2011) Science 334:1518-1524]. However, "Unfortunately, reliably estimating mutual information from finite continuous data remains a significant and unresolved problem" [Kinney JB, Atwal GS (2014) Proc Natl Acad Sci USA 111:3354-3359]. In this paper, we examine the kernel estimation of MI and show that the bandwidths involved should be equalized. We consider a jackknife version of the kernel estimate with equalized bandwidth and allow the bandwidth to vary over an interval. We estimate the MI by the largest value among these kernel estimates and establish the associated theoretical underpinnings.}, } @article {pmid30224465, year = {2018}, author = {}, title = {Correction for Pereyaslavets et al., On the importance of accounting for nuclear quantum effects in ab initio calibrated force fields in biological simulations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9258}, doi = {10.1073/pnas.1814845115}, pmid = {30224465}, issn = {1091-6490}, } @article {pmid30224464, year = {2018}, author = {Zhang, F and Jiang, L and Wang, S}, title = {Repairable cascaded slide-lock system endows bird feathers with tear-resistance and superdurability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10046-10051}, pmid = {30224464}, issn = {1091-6490}, mesh = {Animals ; Birds/*anatomy & histology ; Feathers/*ultrastructure ; }, abstract = {Bird feathers have aroused tremendous attention for their superdurability against tears during long flights through wind and even bushes. Although feathers may inevitably be unzipped, the separated feather vanes can be repaired easily by bill stroking. However, the mechanism underlying bird feathers' superdurability against tears remains unclear. Here, we reveal that the superdurability of bird feathers arises from their repairable cascaded slide-lock system, which is composed of hooklets, a slide rail, and spines at the end of the slide rail as terminating structures. Microscopy with a micronano manipulating system and 3D X-ray microscopy provided high-level visibility into the 3D fine structures and the entire unzipping process of feathers. The hooklets can slide along the slide rail reversibly when suffering external forces, and the sliding hooklet can be locked by the spine at the ends of barbules when larger pulling forces are applied and even slide farther away due to the unzipping of the interlocking structure with large deformation of the barbules. The elongation before separation of adjacent barbs can reach up to 270%, and the separation force can be maintained above 80% of the initial value even after 1,000 cycles of separating and repairing. These results prove that the cascaded slide-lock system ensures the superdurability of bird feathers against tears.}, } @article {pmid30224463, year = {2018}, author = {Chen, NY and Kim, P and Weston, TA and Edillo, L and Tu, Y and Fong, LG and Young, SG}, title = {Fibroblasts lacking nuclear lamins do not have nuclear blebs or protrusions but nevertheless have frequent nuclear membrane ruptures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10100-10105}, pmid = {30224463}, issn = {1091-6490}, support = {P30 DK041301/DK/NIDDK NIH HHS/United States ; R01 AG047192/AG/NIA NIH HHS/United States ; R01 HL126551/HL/NHLBI NIH HHS/United States ; T32 GM065823/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *DNA Damage ; Embryo, Mammalian/*metabolism/ultrastructure ; Fibroblasts/*metabolism/ultrastructure ; Lamins/*deficiency ; Mice ; Mice, Knockout ; Nuclear Envelope/genetics/*metabolism/ultrastructure ; *Stress, Mechanical ; }, abstract = {The nuclear lamina, an intermediate filament meshwork lining the inner nuclear membrane, is formed by the nuclear lamins (lamins A, C, B1, and B2). Defects or deficiencies in individual nuclear lamin proteins have been reported to elicit nuclear blebs (protrusions or outpouchings of the nuclear envelope) and increase susceptibility for nuclear membrane ruptures. It is unclear, however, how a complete absence of nuclear lamins would affect nuclear envelope morphology and nuclear membrane integrity (i.e., whether nuclear membrane blebs or protrusions would occur and, if not, whether cells would be susceptible to nuclear membrane ruptures). To address these issues, we generated mouse embryonic fibroblasts (MEFs) lacking all nuclear lamins. The nuclear lamin-deficient MEFs had irregular nuclear shapes but no nuclear blebs or protrusions. Despite a virtual absence of nuclear blebs, MEFs lacking nuclear lamins had frequent, prolonged, and occasionally nonhealing nuclear membrane ruptures. By transmission electron microscopy, the inner nuclear membrane in nuclear lamin-deficient MEFs have a "wavy" appearance, and there were discrete discontinuities in the inner and outer nuclear membranes. Nuclear membrane ruptures were accompanied by a large increase in DNA damage, as judged by γ-H2AX foci. Mechanical stress increased both nuclear membrane ruptures and DNA damage, whereas minimizing transmission of cytoskeletal forces to the nucleus had the opposite effects.}, } @article {pmid30224462, year = {2018}, author = {Yoshida, K and Shi, S and Ukai-Tadenuma, M and Fujishima, H and Ohno, RI and Ueda, HR}, title = {Leak potassium channels regulate sleep duration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9459-E9468}, pmid = {30224462}, issn = {1091-6490}, mesh = {Animals ; Brain Waves/*physiology ; Mice ; Mice, Knockout ; Potassium Channels/genetics/*metabolism ; Sleep Stages/*physiology ; }, abstract = {A primary goal of sleep research is to understand the molecular basis of sleep. Although some sleep/wake-promoting circuits and secreted substances have been identified, the detailed molecular mechanisms underlying the regulation of sleep duration have been elusive. Here, to address these mechanisms, we developed a simple computational model of a cortical neuron with five channels and a pump, which recapitulates the cortical electrophysiological characteristics of slow-wave sleep (SWS) and wakefulness. Comprehensive bifurcation and detailed mathematical analyses predicted that leak K+ channels play a role in generating the electrophysiological characteristics of SWS, leading to a hypothesis that leak K+ channels play a role in the regulation of sleep duration. To test this hypothesis experimentally, we comprehensively generated and analyzed 14 KO mice, and found that impairment of the leak K+ channel (Kcnk9) decreased sleep duration. Based on these results, we hypothesize that leak K+ channels regulate sleep duration in mammals.}, } @article {pmid30224461, year = {2018}, author = {Kang, Y and Cooper, N and Pandey, P and Scholz, C and O'Donnell, MB and Lieberman, MD and Taylor, SE and Strecher, VJ and Dal Cin, S and Konrath, S and Polk, TA and Resnicow, K and An, L and Falk, EB}, title = {Effects of self-transcendence on neural responses to persuasive messages and health behavior change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9974-9979}, pmid = {30224461}, issn = {1091-6490}, support = {R01 CA180015/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Female ; *Health Behavior ; Humans ; Male ; Prefrontal Cortex/*physiopathology ; *Sedentary Behavior ; }, abstract = {Self-transcendence refers to a shift in mindset from focusing on self-interests to the well-being of others. We offer an integrative neural model of self-transcendence in the context of persuasive messaging by examining the mechanisms of self-transcendence in promoting receptivity to health messages and behavior change. Specifically, we posited that focusing on values and activities that transcend the self can allow people to see that their self-worth is not tied to a specific behavior in question, and in turn become more receptive to subsequent, otherwise threatening health information. To test whether inducing self-transcendent mindsets before message delivery would help overcome defensiveness and increase receptivity, we used two priming tasks, affirmation and compassion, to elicit a transcendent mindset among 220 sedentary adults. As preregistered, those who completed a self-transcendence task before health message exposure, compared with controls, showed greater increases in objectively logged levels of physical activity throughout the following month. In the brain, self-transcendence tasks up-regulated activity in a region of the ventromedial prefrontal cortex, chosen for its role in positive valuation and reward processing. During subsequent health message exposure, self-transcendence priming was associated with increased activity in subregions of the ventromedial prefrontal cortex, implicated in self-related processing and positive valuation, which predicted later decreases in sedentary behavior. The present findings suggest that having a positive self-transcendent mindset can increase behavior change, in part by increasing neural receptivity to health messaging.}, } @article {pmid30224460, year = {2018}, author = {Zhang, F and Wang, Y and Wang, T and Yao, L and Lam, SM and Huang, X and Fan, J and Wang, Q and Liu, L and Jiang, Y and Zhang, H and Shi, L and Yu, M and Shui, G and Wang, Y and Gao, F and Zhang, X and Xu, Z}, title = {cTAGE5/MEA6 plays a critical role in neuronal cellular components trafficking and brain development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9449-E9458}, pmid = {30224460}, issn = {1091-6490}, mesh = {Animals ; Antigens, Neoplasm/genetics/*metabolism ; Astrocytes/cytology/*metabolism ; Biological Transport, Active/genetics ; Brain/cytology/*embryology ; Coat Protein Complex I/genetics/metabolism ; Mice ; Mice, Knockout ; Mutation ; Neoplasm Proteins/genetics/*metabolism ; Neurons/cytology/*metabolism ; }, abstract = {Normal neural development is essential for the formation of neuronal networks and brain function. Cutaneous T cell lymphoma-associated antigen 5 (cTAGE5)/meningioma expressed antigen 6 (MEA6) plays a critical role in the secretion of proteins. However, its roles in the transport of nonsecretory cellular components and in brain development remain unknown. Here, we show that cTAGE5/MEA6 is important for brain development and function. Conditional knockout of cTAGE5/MEA6 in the brain leads to severe defects in neural development, including deficits in dendrite outgrowth and branching, spine formation and maintenance, astrocyte activation, and abnormal behaviors. We reveal that loss of cTAGE5/MEA6 affects the interaction between the coat protein complex II (COPII) components, SAR1 and SEC23, leading to persistent activation of SAR1 and defects in COPII vesicle formation and transport from the endoplasmic reticulum to the Golgi, as well as disturbed trafficking of membrane components in neurons. These defects affect not only the transport of materials required for the development of dendrites and spines but also the signaling pathways required for neuronal development. Because mutations in cTAGE5/MEA6 have been found in patients with Fahr's disease, our study potentially also provides insight into the pathogenesis of this disorder.}, } @article {pmid30224459, year = {2018}, author = {Hoffmann, J and Donoughe, S and Li, K and Salcedo, MK and Rycroft, CH}, title = {A simple developmental model recapitulates complex insect wing venation patterns.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9905-9910}, pmid = {30224459}, issn = {1091-6490}, mesh = {Animals ; Flight, Animal/*physiology ; *Models, Biological ; Odonata/*anatomy & histology/*physiology ; Wings, Animal/*anatomy & histology/*physiology ; }, abstract = {Insect wings are typically supported by thickened struts called veins. These veins form diverse geometric patterns across insects. For many insect species, even the left and right wings from the same individual have veins with unique topological arrangements, and little is known about how these patterns form. We present a large-scale quantitative study of the fingerprint-like "secondary veins." We compile a dataset of wings from 232 species and 17 families from the order Odonata (dragonflies and damselflies), a group with particularly elaborate vein patterns. We characterize the geometric arrangements of veins and develop a simple model of secondary vein patterning. We show that our model is capable of recapitulating the vein geometries of species from other, distantly related winged insect clades.}, } @article {pmid30224458, year = {2018}, author = {Blaesi, EJ and Palowitch, GM and Hu, K and Kim, AJ and Rose, HR and Alapati, R and Lougee, MG and Kim, HJ and Taguchi, AT and Tan, KO and Laremore, TN and Griffin, RG and Krebs, C and Matthews, ML and Silakov, A and Bollinger, JM and Allen, BD and Boal, AK}, title = {Metal-free class Ie ribonucleotide reductase from pathogens initiates catalysis with a tyrosine-derived dihydroxyphenylalanine radical.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10022-10027}, pmid = {30224458}, issn = {1091-6490}, support = {F32 GM116353/GM/NIGMS NIH HHS/United States ; R35 GM119707/GM/NIGMS NIH HHS/United States ; S10 OD012289/OD/NIH HHS/United States ; }, mesh = {Dihydroxyphenylalanine/*chemistry/metabolism ; Escherichia coli/*enzymology ; Escherichia coli Proteins/*chemistry/metabolism ; Free Radicals/*chemistry/metabolism ; Ribonucleotide Reductases/*chemistry/metabolism ; Tyrosine/*chemistry/metabolism ; }, abstract = {All cells obtain 2'-deoxyribonucleotides for DNA synthesis through the activity of a ribonucleotide reductase (RNR). The class I RNRs found in humans and pathogenic bacteria differ in (i) use of Fe(II), Mn(II), or both for activation of the dinuclear-metallocofactor subunit, β; (ii) reaction of the reduced dimetal center with dioxygen or superoxide for this activation; (iii) requirement (or lack thereof) for a flavoprotein activase, NrdI, to provide the superoxide from O2; and (iv) use of either a stable tyrosyl radical or a high-valent dimetal cluster to initiate each turnover by oxidizing a cysteine residue in the α subunit to a radical (Cys•). The use of manganese by bacterial class I, subclass b-d RNRs, which contrasts with the exclusive use of iron by the eukaryotic Ia enzymes, appears to be a countermeasure of certain pathogens against iron deprivation imposed by their hosts. Here, we report a metal-free type of class I RNR (subclass e) from two human pathogens. The Cys• in its α subunit is generated by a stable, tyrosine-derived dihydroxyphenylalanine radical (DOPA•) in β. The three-electron oxidation producing DOPA• occurs in Escherichia coli only if the β is coexpressed with the NrdI activase encoded adjacently in the pathogen genome. The independence of this new RNR from transition metals, or the requirement for a single metal ion only transiently for activation, may afford the pathogens an even more potent countermeasure against transition metal-directed innate immunity.}, } @article {pmid30224457, year = {2018}, author = {Müller, A and Hennig, A and Lorscheid, S and Grondona, P and Schulze-Osthoff, K and Hailfinger, S and Kramer, D}, title = {IκBζ is a key transcriptional regulator of IL-36-driven psoriasis-related gene expression in keratinocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10088-10093}, pmid = {30224457}, issn = {1091-6490}, mesh = {Adaptor Proteins, Signal Transducing/genetics/immunology/*metabolism ; Animals ; *Cell Proliferation ; *Gene Expression Regulation ; Humans ; Interleukin-1/genetics/immunology/*metabolism ; Keratinocytes/immunology/pathology ; Mice ; Mice, Knockout ; NF-kappa B/genetics/immunology/metabolism ; Nuclear Proteins/genetics/immunology/*metabolism ; Psoriasis/genetics/immunology/*metabolism/pathology ; STAT3 Transcription Factor/genetics/immunology/metabolism ; *Signal Transduction ; }, abstract = {Proinflammatory cytokine signaling in keratinocytes plays a crucial role in the pathogenesis of psoriasis, a skin disease characterized by hyperproliferation and abnormal differentiation of keratinocytes and infiltration of inflammatory cells. Although IL-17A and TNFα are effective therapeutic targets in psoriasis, IL-36 has recently emerged as a proinflammatory cytokine. However, little is known about IL-36 signaling and its downstream transcriptional responses. Here, we found that exposure of keratinocytes to IL-36 induced the expression of IκBζ, an atypical IκB member and a specific transcriptional regulator of selective NF-κB target genes. Induction of IκBζ by IL-36 was mediated by NF-κB and STAT3. In agreement, IL-36-mediated induction of IκBζ was found to be required for the expression of various psoriasis-related genes involved in inflammatory signaling, neutrophil chemotaxis, and leukocyte activation. Importantly, IκBζ-knockout mice were protected against IL-36-mediated dermatitis, accompanied by reduced proinflammatory gene expression, decreased immune cell infiltration, and a lack of keratinocyte hyperproliferation. Moreover, expression of IκBζ mRNA was highly up-regulated in biopsies of psoriasis patients where it coincided with IL36G levels. Thus our results uncover an important role for IκBζ in IL-36 signaling and validate IκBζ as an attractive target for psoriasis therapy.}, } @article {pmid30224456, year = {2018}, author = {Wang, WM and Sheng, ZM and Gibbon, P and Chen, LM and Li, YT and Zhang, J}, title = {Collimated ultrabright gamma rays from electron wiggling along a petawatt laser-irradiated wire in the QED regime.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9911-9916}, pmid = {30224456}, issn = {1091-6490}, abstract = {Even though high-quality X- and gamma rays with photon energy below mega-electron volt (MeV) are available from large-scale X-ray free electron lasers and synchrotron radiation facilities, it remains a great challenge to generate bright gamma rays over 10 MeV. Recently, gamma rays with energies up to the MeV level were observed in Compton scattering experiments based on laser wakefield accelerators, but the yield efficiency was as low as [Formula: see text], owing to low charge of the electron beam. Here, we propose a scheme to efficiently generate gamma rays of hundreds of MeV from submicrometer wires irradiated by petawatt lasers, where electron accelerating and wiggling are achieved simultaneously. The wiggling is caused by the quasistatic electric and magnetic fields induced around the wire surface, and these are so high that even quantum electrodynamics (QED) effects become significant for gamma-ray generation, although the driving lasers are only at the petawatt level. Our full 3D simulations show that directional, ultrabright gamma rays are generated, containing [Formula: see text] photons between 5 and 500 MeV within a 10-fs duration. The brilliance, up to [Formula: see text] photons [Formula: see text] per 0.1% bandwidth at an average photon energy of 20 MeV, is second only to X-ray free electron lasers, while the photon energy is 3 orders of magnitude higher than the latter. In addition, the gamma ray yield efficiency approaches 10%-that is, 5 orders of magnitude higher than the Compton scattering based on laser wakefield accelerators. Such high-energy, ultrabright, femtosecond-duration gamma rays may find applications in nuclear photonics, radiotherapy, and laboratory astrophysics.}, } @article {pmid30224455, year = {2018}, author = {Farías-Rico, JA and Ruud Selin, F and Myronidi, I and Frühauf, M and von Heijne, G}, title = {Effects of protein size, thermodynamic stability, and net charge on cotranslational folding on the ribosome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9280-E9287}, pmid = {30224455}, issn = {1091-6490}, mesh = {Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Mutation ; Protein Biosynthesis/*physiology ; Protein Domains ; *Protein Folding ; Protein Stability ; Ribosomal Proteins/genetics/*metabolism ; Ribosomes/genetics/*metabolism ; }, abstract = {During the last five decades, studies of protein folding in dilute buffer solutions have produced a rich picture of this complex process. In the cell, however, proteins can start to fold while still attached to the ribosome (cotranslational folding) and it is not yet clear how the ribosome affects the folding of protein domains of different sizes, thermodynamic stabilities, and net charges. Here, by using arrest peptides as force sensors and on-ribosome pulse proteolysis, we provide a comprehensive picture of how the distance from the peptidyl transferase center in the ribosome at which proteins fold correlates with protein size. Moreover, an analysis of a large collection of mutants of the Escherichia coli ribosomal protein S6 shows that the force exerted on the nascent chain by protein folding varies linearly with the thermodynamic stability of the folded state, and that the ribosome environment disfavors folding of domains of high net-negative charge.}, } @article {pmid30224454, year = {2018}, author = {Oberhofer, G and Ivy, T and Hay, BA}, title = {Behavior of homing endonuclease gene drives targeting genes required for viability or female fertility with multiplexed guide RNAs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9343-E9352}, pmid = {30224454}, issn = {1091-6490}, support = {T32 GM007616/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *CRISPR-Cas Systems ; Drosophila melanogaster ; Female ; Fertility/genetics ; *Gene Targeting ; }, abstract = {A gene drive method of particular interest for population suppression utilizes homing endonuclease genes (HEGs), wherein a site-specific, nuclease-encoding cassette is copied, in the germline, into a target gene whose loss of function results in loss of viability or fertility in homozygous, but not heterozygous, progeny. Earlier work in Drosophila and mosquitoes utilized HEGs consisting of Cas9 and a single guide RNA (gRNA) that together target a specific gene for cleavage. Homing was observed, but resistant alleles immune to cleavage, while retaining wild-type gene function, were also created through nonhomologous end joining. Such alleles prevent drive and population suppression. Targeting a gene for cleavage at multiple positions has been suggested as a strategy to prevent the appearance of resistant alleles. To test this hypothesis, we generated two suppression HEGs in Drosophila melanogaster targeting genes required for embryonic viability or fertility, using a HEG consisting of CRISPR/Cas9 and gRNAs designed to cleave each gene at four positions. Rates of target locus cleavage were very high, and multiplexing of gRNAs prevented resistant allele formation. However, germline homing rates were modest, and the HEG cassette was unstable during homing events, resulting in frequent partial copying of HEGs that lacked gRNAs, a dominant marker gene, or Cas9. Finally, in drive experiments, the HEGs failed to spread due to the high fitness load induced in offspring as a result of maternal carryover of Cas9/gRNA complex activity. Alternative design principles are proposed that may mitigate these problems in future gene drive engineering.}, } @article {pmid30224453, year = {2018}, author = {Sun, J and Paduch, M and Kim, SA and Kramer, RM and Barrios, AF and Lu, V and Luke, J and Usatyuk, S and Kossiakoff, AA and Tan, S}, title = {Structural basis for activation of SAGA histone acetyltransferase Gcn5 by partner subunit Ada2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10010-10015}, pmid = {30224453}, issn = {1091-6490}, support = {R01 GM088236/GM/NIGMS NIH HHS/United States ; U54 HG006436/HG/NHGRI NIH HHS/United States ; R01 GM111651/GM/NIGMS NIH HHS/United States ; U01 GM094588/GM/NIGMS NIH HHS/United States ; R01 GM072688/GM/NIGMS NIH HHS/United States ; R01 GM117372/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetyl Coenzyme A/*chemistry/metabolism ; Crystallography, X-Ray ; Enzyme Activation ; Histone Acetyltransferases/*chemistry/metabolism ; Histones/*chemistry/metabolism ; Protein Binding ; Protein Domains ; Saccharomyces cerevisiae/*chemistry/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism ; Transcription Factors/*chemistry/metabolism ; }, abstract = {The Gcn5 histone acetyltransferase (HAT) subunit of the SAGA transcriptional coactivator complex catalyzes acetylation of histone H3 and H2B N-terminal tails, posttranslational modifications associated with gene activation. Binding of the SAGA subunit partner Ada2 to Gcn5 activates Gcn5's intrinsically weak HAT activity on histone proteins, but the mechanism for this activation by the Ada2 SANT domain has remained elusive. We have employed Fab antibody fragments as crystallization chaperones to determine crystal structures of a yeast Ada2/Gcn5 complex. Our structural and biochemical results indicate that the Ada2 SANT domain does not activate Gcn5's activity by directly affecting histone peptide binding as previously proposed. Instead, the Ada2 SANT domain enhances Gcn5 binding of the enzymatic cosubstrate acetyl-CoA. This finding suggests a mechanism for regulating chromatin modification enzyme activity: controlling binding of the modification cosubstrate instead of the histone substrate.}, } @article {pmid30224452, year = {2018}, author = {Stevenson, RF and Zheng, J and Mnatsakanyan, L and Vadera, S and Knight, RT and Lin, JJ and Yassa, MA}, title = {Hippocampal CA1 gamma power predicts the precision of spatial memory judgments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10148-10153}, pmid = {30224452}, issn = {1091-6490}, support = {R01 MH102392/MH/NIMH NIH HHS/United States ; R21 AG049220/AG/NIA NIH HHS/United States ; T32 NS045540/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; *CA1 Region, Hippocampal/diagnostic imaging/physiology ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Middle Aged ; *Prefrontal Cortex/diagnostic imaging/physiology ; Spatial Memory/*physiology ; }, abstract = {The hippocampus plays a critical role in spatial memory. However, the exact neural mechanisms underlying high-fidelity spatial memory representations are unknown. We report findings from presurgical epilepsy patients with bilateral hippocampal depth electrodes performing an object-location memory task that provided a broad range of spatial memory precision. During encoding, patients were shown a series of objects along the circumference of an invisible circle. At test, the same objects were shown at the top of the circle (0°), and patients used a dial to move the object to its location shown during encoding. Angular error between the correct location and the indicated location was recorded as a continuous measure of performance. By registering pre- and postimplantation MRI scans, we were able to localize the electrodes to specific hippocampal subfields. We found a correlation between increased gamma power, thought to reflect local excitatory activity, and the precision of spatial memory retrieval in hippocampal CA1 electrodes. Additionally, we found a similar relationship between gamma power and memory precision in the dorsolateral prefrontal cortex and a directional relationship between activity in this region and in the CA1, suggesting that the dorsolateral prefrontal cortex is involved in postretrieval processing. These results indicate that local processing in hippocampal CA1 and dorsolateral prefrontal cortex supports high-fidelity spatial memory representations.}, } @article {pmid30224451, year = {2018}, author = {Lopetuso, LR and De Salvo, C and Pastorelli, L and Rana, N and Senkfor, HN and Petito, V and Di Martino, L and Scaldaferri, F and Gasbarrini, A and Cominelli, F and Abbott, DW and Goodman, WA and Pizarro, TT}, title = {IL-33 promotes recovery from acute colitis by inducing miR-320 to stimulate epithelial restitution and repair.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9362-E9370}, pmid = {30224451}, issn = {1091-6490}, support = {P01 DK091222/DK/NIDDK NIH HHS/United States ; P30 DK097948/DK/NIDDK NIH HHS/United States ; R01 DK056762/DK/NIDDK NIH HHS/United States ; R37 DK042191/DK/NIDDK NIH HHS/United States ; R56 DK042191/DK/NIDDK NIH HHS/United States ; R01 DK042191/DK/NIDDK NIH HHS/United States ; }, mesh = {Acute Disease ; Animals ; Caco-2 Cells ; Colitis/chemically induced/genetics/*metabolism/pathology ; Dextran Sulfate/toxicity ; Humans ; Inflammatory Bowel Diseases/chemically induced/genetics/*metabolism/pathology ; Interleukin-1 Receptor-Like 1 Protein/genetics/metabolism ; Interleukin-33/genetics/*metabolism ; Intestinal Mucosa/*physiology ; Mice ; Mice, Knockout ; MicroRNAs/genetics/*metabolism ; *Regeneration ; }, abstract = {Defective and/or delayed wound healing has been implicated in the pathogenesis of several chronic inflammatory disorders, including inflammatory bowel disease (IBD). The resolution of inflammation is particularly important in mucosal organs, such as the gut, where restoration of epithelial barrier function is critical to reestablish homeostasis with the interfacing microenvironment. Although IL-33 and its receptor ST2/ILRL1 are known to be increased and associated with IBD, studies using animal models of colitis to address the mechanism have yielded ambiguous results, suggesting both pathogenic and protective functions. Unlike those previously published studies, we focused on the functional role of IL-33/ST2 during an extended (2-wk) recovery period after initial challenge in dextran sodium sulfate (DSS)-induced colitic mice. Our results show that during acute, resolving colitis the normal function of endogenous IL-33 is protection, and the lack of either IL-33 or ST2 impedes the overall recovery process, while exogenous IL-33 administration during recovery dramatically accelerates epithelial restitution and repair, with concomitant improvement of colonic inflammation. Mechanistically, we show that IL-33 stimulates the expression of a network of microRNAs (miRs) in the Caco2 colonic intestinal epithelial cell (IEC) line, especially miR-320, which is increased by >16-fold in IECs isolated from IL-33-treated vs. vehicle-treated DSS colitic mice. Finally, IL-33-dependent in vitro proliferation and wound closure of Caco-2 IECs is significantly abrogated after specific inhibition of miR-320A. Together, our data indicate that during acute, resolving colitis, IL-33/ST2 plays a crucial role in gut mucosal healing by inducing epithelial-derived miR-320 that promotes epithelial repair/restitution and the resolution of inflammation.}, } @article {pmid30224294, year = {2018}, author = {Leeming, W and Barahona, A}, title = {Synthesis, convergence, and differences in the entangled histories of cytogenetics in medicine: A comparative study of Canada and Mexico.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {71}, number = {}, pages = {8-16}, doi = {10.1016/j.shpsc.2018.08.002}, pmid = {30224294}, issn = {1879-2499}, mesh = {Canada ; Cytogenetics/*history ; History of Medicine ; History, 20th Century ; Humans ; Mexico ; }, abstract = {Most historians of science and medicine agree that medical interest in genetics intensified after 1930, and interest in the relationship of radiation damage and genetics continued and expanded after World War II. Moreover, they maintain that the synthesis and convergence of human genetics and cytological techniques in European centers resulted in their dissemination to centers in the United States, resulting in a new field of expertise focused on medicine and clinical research, known as cytogenetics. In this article, we broaden the scope of the inquiry by showing how the early histories of cytogenetics in Canada and Mexico unfolded against strikingly different backgrounds in clinical research and the delivery of health care. We thus argue that the field of cytogenetics did not emerge in a straightforward manner and develop in the same way in all countries. The article provides a brief background to the history of human cytogenetics, and then outlines key developments related to the early adoption of cytogenetics in Canada and Mexico. Conclusions are then drawn using comparisons of the different ways in which local determinants affected adoption. We then propose directions for future study focused on the ways in which circuits of practices, collaborative research, and transfers of knowledge have shaped how cytogenetics has come to be organised in medicine around the world.}, } @article {pmid30224157, year = {2019}, author = {Saranathan, N and Vivekanandan, P}, title = {G-Quadruplexes: More Than Just a Kink in Microbial Genomes.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {148-163}, doi = {10.1016/j.tim.2018.08.011}, pmid = {30224157}, issn = {1878-4380}, abstract = {G-quadruplexes (G4s) are noncanonical nucleic acid secondary structures formed by guanine-rich DNA and RNA sequences. In this review we aim to provide an overview of the biological roles of G4s in microbial genomes with emphasis on recent discoveries. G4s are enriched and conserved in the regulatory regions of microbes, including bacteria, fungi, and viruses. Importantly, G4s in hepatitis B virus (HBV) and hepatitis C virus (HCV) genomes modulate genes crucial for virus replication. Recent studies on Epstein-Barr virus (EBV) shed light on the role of G4s within the microbial transcripts as cis-acting regulatory signals that modulate translation and facilitate immune evasion. Furthermore, G4s in microbial genomes have been linked to radioresistance, antigenic variation, recombination, and latency. G4s in microbial genomes represent novel therapeutic targets for antimicrobial therapy.}, } @article {pmid30224089, year = {2018}, author = {Carthey, AJR and Gillings, MR and Blumstein, DT}, title = {The Extended Genotype: Microbially Mediated Olfactory Communication.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {885-894}, doi = {10.1016/j.tree.2018.08.010}, pmid = {30224089}, issn = {1872-8383}, abstract = {Microbes are now known to influence inter- and intraspecific olfactory signaling systems. They do so by producing metabolites that function as odorants. A unique attribute of such odorants is that they arise as a product of microbial-host interactions. These interactions need not be mutualistic, and indeed can be antagonistic. We develop an integrated ecoevolutionary model to explore microbially mediated olfactory communication and a process model that illustrates the various ways that microbial products might contribute to odorants. This novel approach generates testable predictions, including that selection to incorporate microbial products should be a common feature of infochemicals that communicate identity but not those that communicate fitness or quality. Microbes extend an individual's genotype, but also enhance vulnerability to environmental change.}, } @article {pmid30223906, year = {2018}, author = {Bredon, M and Dittmer, J and Noël, C and Moumen, B and Bouchon, D}, title = {Lignocellulose degradation at the holobiont level: teamwork in a keystone soil invertebrate.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {162}, pmid = {30223906}, issn = {2049-2618}, abstract = {BACKGROUND: Woodlice are recognized as keystone species in terrestrial ecosystems due to their role in the decomposition of organic matter. Thus, they contribute to lignocellulose degradation and nutrient cycling in the environment together with other macroarthropods. Lignocellulose is the main component of plants and is composed of cellulose, lignin and hemicellulose. Its digestion requires the action of multiple Carbohydrate-Active enZymes (called CAZymes), typically acting together as a cocktail with complementary, synergistic activities and modes of action. Some invertebrates express a few endogenous lignocellulose-degrading enzymes but in most species, an efficient degradation and digestion of lignocellulose can only be achieved through mutualistic associations with endosymbionts. Similar to termites, it has been suspected that several bacterial symbionts may be involved in lignocellulose degradation in terrestrial isopods, by completing the CAZyme repertoire of their hosts.

RESULTS: To test this hypothesis, host transcriptomic and microbiome shotgun metagenomic datasets were obtained and investigated from the pill bug Armadillidium vulgare. Many genes of bacterial and archaeal origin coding for CAZymes were identified in the metagenomes of several host tissues and the gut content of specimens from both laboratory lineages and a natural population of A. vulgare. Some of them may be involved in the degradation of cellulose, hemicellulose, and lignin. Reconstructing a lignocellulose-degrading microbial community based on the prokaryotic taxa contributing relevant CAZymes revealed two taxonomically distinct but functionally redundant microbial communities depending on host origin. In parallel, endogenous CAZymes were identified from the transcriptome of the host and their expression in digestive tissues was demonstrated by RT-qPCR, demonstrating a complementary enzyme repertoire for lignocellulose degradation from both the host and the microbiome in A. vulgare.

CONCLUSIONS: Our results provide new insights into the role of the microbiome in the evolution of terrestrial isopods and their adaptive radiation in terrestrial habitats.}, } @article {pmid30223892, year = {2018}, author = {Sitaraman, R}, title = {Prokaryotic horizontal gene transfer within the human holobiont: ecological-evolutionary inferences, implications and possibilities.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {163}, pmid = {30223892}, issn = {2049-2618}, abstract = {The ubiquity of horizontal gene transfer in the living world, especially among prokaryotes, raises interesting and important scientific questions regarding its effects on the human holobiont i.e., the human and its resident bacterial communities considered together as a unit of selection. Specifically, it would be interesting to determine how particular gene transfer events have influenced holobiont phenotypes in particular ecological niches and, conversely, how specific holobiont phenotypes have influenced gene transfer events. In this synthetic review, we list some notable and recent discoveries of horizontal gene transfer among the prokaryotic component of the human microbiota, and analyze their potential impact on the holobiont from an ecological-evolutionary viewpoint. Finally, the human-Helicobacter pylori association is presented as an illustration of these considerations, followed by a delineation of unresolved questions and avenues for future research.}, } @article {pmid30223889, year = {2018}, author = {Jarett, JK and Nayfach, S and Podar, M and Inskeep, W and Ivanova, NN and Munson-McGee, J and Schulz, F and Young, M and Jay, ZJ and Beam, JP and Kyrpides, NC and Malmstrom, RR and Stepanauskas, R and Woyke, T}, title = {Single-cell genomics of co-sorted Nanoarchaeota suggests novel putative host associations and diversification of proteins involved in symbiosis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {161}, pmid = {30223889}, issn = {2049-2618}, abstract = {BACKGROUND: Nanoarchaeota are obligate symbionts of other Archaea first discovered 16 years ago, yet little is known about this largely uncultivated taxon. While Nanoarchaeota diversity has been detected in a variety of habitats using 16S rRNA gene surveys, genome sequences have been available for only three Nanoarchaeota and their hosts. The host range and adaptation of Nanoarchaeota to a wide range of environmental conditions has thus largely remained elusive. Single-cell genomics is an ideal approach to address these questions as Nanoarchaeota can be isolated while still attached to putative hosts, enabling the exploration of cell-cell interactions and fine-scale genomic diversity.

RESULTS: From 22 single amplified genomes (SAGs) from three hot springs in Yellowstone National Park, we derived a genome-based phylogeny of the phylum Nanoarchaeota, linking it to global 16S rRNA gene diversity. By exploiting sequencing of co-sorted tightly attached cells, we associated Nanoarchaeota with 6 novel putative hosts, 2 of which were found in multiple SAGs, and showed that the same host species may associate with multiple species of Nanoarchaeota. Comparison of single nucleotide polymorphisms (SNPs) within a population of Nanoarchaeota SAGs indicated that Nanoarchaeota attached to a single host cell in situ are likely clonal. In addition to an overall pattern of purifying selection, we found significantly higher densities of non-synonymous SNPs in hypothetical cell surface proteins, as compared to other functional categories. Genes implicated in interactions in other obligate microbe-microbe symbioses, including those encoding a cytochrome bd-I ubiquinol oxidase and a FlaJ/TadC homologue possibly involved in type IV pili production, also had relatively high densities of non-synonymous SNPs.

CONCLUSIONS: This population genetics study of Nanoarchaeota greatly expands the known potential host range of the phylum and hints at what genes may be involved in adaptation to diverse environments or different hosts. We provide the first evidence that Nanoarchaeota cells attached to the same host cell are clonal and propose a hypothesis for how clonality may occur despite diverse symbiont populations.}, } @article {pmid30223888, year = {2018}, author = {Flaherty, BR and Talundzic, E and Barratt, J and Kines, KJ and Olsen, C and Lane, M and Sheth, M and Bradbury, RS}, title = {Restriction enzyme digestion of host DNA enhances universal detection of parasitic pathogens in blood via targeted amplicon deep sequencing.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {164}, pmid = {30223888}, issn = {2049-2618}, abstract = {BACKGROUND: Targeted amplicon deep sequencing (TADS) of the 16S rRNA gene is commonly used to explore and characterize bacterial microbiomes. Meanwhile, attempts to apply TADS to the detection and characterization of entire parasitic communities have been hampered since conserved regions of many conserved parasite genes, such as the 18S rRNA gene, are also conserved in their eukaryotic hosts. As a result, targeted amplification of 18S rRNA from clinical samples using universal primers frequently results in competitive priming and preferential amplification of host DNA. Here, we describe a novel method that employs a single pair of universal primers to capture all blood-borne parasites while reducing host 18S rRNA template and enhancing the amplification of parasite 18S rRNA for TADS. This was achieved using restriction enzymes to digest the 18S rRNA gene at cut sites present only in the host sequence prior to PCR amplification.

RESULTS: This method was validated against 16 species of blood-borne helminths and protozoa. Enzyme digestion prior to PCR enrichment and Illumina amplicon deep sequencing led to a substantial reduction in human reads and a corresponding 5- to 10-fold increase in parasite reads relative to undigested samples. This method allowed for discrimination of all common parasitic agents found in human blood, even in cases of multi-parasite infection, and markedly reduced the limit of detection in digested versus undigested samples.

CONCLUSIONS: The results herein provide a novel methodology for the reduction of host DNA prior to TADS and establish the validity of a next-generation sequencing-based platform for universal parasite detection.}, } @article {pmid30223880, year = {2018}, author = {Kasozi, KI and Namubiru, S and Kiconco, O and Kinyi, HW and Ssempijja, F and Ezeonwumelu, JOC and Ninsiima, HI and Okpanachi, AO}, title = {Low concentrations of monosodium glutamate (MSG) are safe in male Drosophila melanogaster.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {670}, pmid = {30223880}, issn = {1756-0500}, mesh = {Animals ; Catalase/drug effects/metabolism ; *Drosophila melanogaster ; Hydrogen/metabolism ; Longevity ; Male ; Sodium Glutamate/*toxicity ; }, abstract = {OBJECTIVE: Monosodium glutamate (MSG) has been marred by a lot of controversy on its safety. In a majority of experimental studies, administration of the compound has been parenteral, and yet little is known about MSG safety consumed as a food supplement. In this study, we assessed the effects of low concentrations of MSG on the activity of hydrogen scavenging, catalase activity and climbing as well as lifespan in male Drosophila melanogaster over a 30 days period since this has been sparsely studied.

RESULTS: No significant differences were associated with MSG at 5%, 1%, 0.2%, 0.04% on hydrogen peroxide scavenging, negative geotaxis and lifespan in W1118 male D. melanogaster. Significant differences were found in 5% MSG on catalase activity, showing that high MSG concentrations would affect tissue health in male D. melanogaster. MSG consumed as a food supplement would be safe at concentrations below 5% MSG.}, } @article {pmid30223872, year = {2018}, author = {Fite, RO and Mohammedamin, A and Abebe, TW}, title = {Unintended pregnancy and associated factors among pregnant women in Arsi Negele Woreda, West Arsi Zone, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {671}, pmid = {30223872}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; *Contraception ; *Counseling ; Cross-Sectional Studies ; Ethiopia ; Female ; Humans ; Male ; Parity ; Pregnancy ; *Pregnancy, Unplanned ; Young Adult ; }, abstract = {OBJECTIVE: The study was aimed at determining the prevalence of unintended pregnancy and associated factors in Arsi Negele Woreda from May 01, 2017 to July 30, 2017.

RESULTS: Unintended pregnancy was found to be 41.5%. The multivariable logistic regression revealed that 35 and above age group (AOR; 2.343, 95% CI 1.374, 3.997), single marital status (AOR; 6.492, 95% CI 1.299, 32.455), parity of 2 (AOR; 53.419, 95% CI 21.453, 133.014), parity of 3 and above (AOR; 20.219, 95% CI 7.915, 51.655), having abortion history (AOR; 1.962, 95% CI 1.025, 3.755), having health professional visit (AOR; 2.004, 95% CI 1.218, 3.298) and having autonomy to use contraceptive method (AOR; 2.925, 95% CI 1.648, 5.190) were significantly associated with unintended pregnancy. Therefore, reproductive health advocacy, counseling and access of modern contraceptive methods are recommended.}, } @article {pmid30223871, year = {2018}, author = {Seid, E and Derseh, L and Derso, T and Assefa, M and Gonete, KA and Tariku, A}, title = {Nutrient consumption and associated factors among school age children in Dewa Chefe District, northeast Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {669}, pmid = {30223871}, issn = {1756-0500}, mesh = {Child ; Cross-Sectional Studies ; *Diet ; Ethiopia ; Female ; Food ; Humans ; Male ; *Nutritional Status ; Odds Ratio ; Prevalence ; }, abstract = {BACKGROUND: Inadequate nutrient consumption causes protein energy malnutrition and micronutrient deficiencies and related consequences, including poor physical growth and intellectual development. However, literatures showing quantitative measurement of dietary intake of children are limited in Ethiopia. Therefore, this study investigated nutrient consumption and associated factors among school age children (7-9 years) in Dewa Cheffe District, northeast of Ethiopia.

METHODS: A community based cross-sectional study was conducted from November to December, 2015 in Dewa Cheffe District. A multistage sampling technique was used to select 605 study subjects. Pre-tested and structured questionnaire was used to collect data. A 24-h dietary recall with portion size estimation method was used to assess nutrient consumption of school age children. Multivariable logistic regression analysis was fitted to identify factors associated with inadequate energy intake. adjusted odds ratio (AOR) with corresponding 95% confidence interval was computed to show the strength of association. In multivariable analysis, a P value of < 0.05 was used to declare statistically significance.

RESULTS: A total of 600 school age children were included in the study. About 29% [95%, CI 21.9, 36.1] of study participants had inadequate energy intake. The result of multivariable analysis revealed that, children who were belonged to a female headed households [AOR = 3.65; 95% CI 1.20, 11.04] and family size of six and above [AOR = 14.42; 95% CI 4.65, 44.67] were found with increased odds of inadequate energy consumption. In contrast, decreased odds of inadequate energy consumption were observed among children whose mothers were housewives [AOR = 0.32; 95% CI 0.11, 0.52].

CONCLUSIONS: In this study, one-third of school children had inadequate energy consumption. Female headed households, being in the larger family size and housewives mother were significantly associated with inadequate energy consumption. Therefore, giving special focus to female headed households, large family and outdoor worker mothers will help to improve dietary intake of children.}, } @article {pmid30223853, year = {2018}, author = {Fabre, PJ and Leleu, M and Mascrez, B and Lo Giudice, Q and Cobb, J and Duboule, D}, title = {Heterogeneous combinatorial expression of Hoxd genes in single cells during limb development.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {101}, pmid = {30223853}, issn = {1741-7007}, abstract = {BACKGROUND: Global analyses of gene expression during development reveal specific transcription patterns associated with the emergence of various cell types, tissues, and organs. These heterogeneous patterns are instrumental to ensure the proper formation of the different parts of our body, as shown by the phenotypic effects generated by functional genetic approaches. However, variations at the cellular level can be observed within each structure or organ. In the developing mammalian limbs, expression of Hox genes from the HoxD cluster is differentially controlled in space and time, in cells that will pattern the digits and the forearms. While the Hoxd genes broadly share a common regulatory landscape and large-scale analyses have suggested a homogenous Hox gene transcriptional program, it has not previously been clear whether Hoxd genes are expressed together at the same levels in the same cells.

RESULTS: We report a high degree of heterogeneity in the expression of the Hoxd11 and Hoxd13 genes. We analyzed single-limb bud cell transcriptomes and show that Hox genes are expressed in specific combinations that appear to match particular cell types. In cells giving rise to digits, we find that the expression of the five relevant Hoxd genes (Hoxd9 to Hoxd13) is unbalanced, despite their control by known global enhancers. We also report that specific combinatorial expression follows a pseudo-time sequence, which is established based on the transcriptional diversity of limb progenitors.

CONCLUSIONS: Our observations reveal the existence of distinct combinations of Hoxd genes at the single-cell level during limb development. In addition, we document that the increasing combinatorial expression of Hoxd genes in this developing structure is associated with specific transcriptional signatures and that these signatures illustrate a temporal progression in the differentiation of these cells.}, } @article {pmid30223795, year = {2018}, author = {Peripolli, E and Metzger, J and de Lemos, MVA and Stafuzza, NB and Kluska, S and Olivieri, BF and Feitosa, FLB and Berton, MP and Lopes, FB and Munari, DP and Lôbo, RB and Magnabosco, CU and Di Croce, F and Osterstock, J and Denise, S and Pereira, ASC and Baldi, F}, title = {Autozygosity islands and ROH patterns in Nellore lineages: evidence of selection for functionally important traits.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {680}, pmid = {30223795}, issn = {1471-2164}, support = {2016/22013-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Animals ; Brazil ; Cattle/*genetics ; Genetic Linkage ; Genome ; Genomics/methods ; Genotype ; *Homozygote ; *Inbreeding ; Male ; Pedigree ; Phenotype ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: The aim of this study was to assess genome-wide autozygosity in a Nellore cattle population and to characterize ROH patterns and autozygosity islands that may have occurred due to selection within its lineages. It attempts also to compare estimates of inbreeding calculated from ROH (FROH), genomic relationship matrix (FGRM), and pedigree-based coefficient (FPED).

RESULTS: The average number of ROH per animal was 55.15 ± 13.01 with an average size of 3.24 Mb. The Nellore genome is composed mostly by a high number of shorter segments accounting for 78% of all ROH, although the proportion of the genome covered by them was relatively small. The genome autozygosity proportion indicates moderate to high inbreeding levels for classical standards, with an average value of 7.15% (178.70 Mb). The average of FPED and FROH, and their correlations (- 0.05 to 0.26) were low. Estimates of correlation between FGRM-FPED was zero, while the correlation (- 0.01 to - 0.07) between FGRM-FROH decreased as a function of ROH length, except for FROH > 8Mb (- 0.03). Overall, inbreeding coefficients were not high for the genotyped animals. Autozygosity islands were evident across the genome (n = 62) and their genomic location did not largely differ within lineages. Enriched terms (p < 0.01) associated with defense response to bacteria (GO:0042742), immune complex reaction (GO:0045647), pregnancy-associated glycoproteins genes (GO:0030163), and organism growth (GO:0040014) were described within the autozygotic islands.

CONCLUSIONS: Low FPED-FROH correlation estimates indicate that FPED is not the most suitable method for capturing ancient inbreeding when the pedigree does not extend back many generations and FROH should be used instead. Enriched terms (p < 0.01) suggest a strong selection for immune response. Non-overlapping islands within the lineages greatly explain the mechanism underlying selection for functionally important traits in Nellore cattle.}, } @article {pmid30223794, year = {2018}, author = {Khatri, B and Seo, D and Shouse, S and Pan, JH and Hudson, NJ and Kim, JK and Bottje, W and Kong, BC}, title = {MicroRNA profiling associated with muscle growth in modern broilers compared to an unselected chicken breed.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {683}, pmid = {30223794}, issn = {1471-2164}, support = {2013-01953//USDA-NIFA/ ; }, mesh = {Animals ; Breast/growth & development ; *Breeding ; Chickens/*genetics/growth & development ; Cluster Analysis ; Computational Biology ; *Gene Expression Regulation ; Male ; Metabolic Networks and Pathways ; MicroRNAs/classification/*genetics/*metabolism ; Muscle Development/*genetics ; RNA, Messenger/genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Genetically selected modern broiler chickens have acquired outstanding production efficiency through rapid growth and improved feed efficiency compared to unselected chicken breeds. Recently, we analyzed the transcriptome of breast muscle tissues obtained from modern pedigree male (PeM) broilers (rapid growth and higher efficiency) and foundational Barred Plymouth Rock (BPR) chickens (slow growth and poorer efficiency). This study was designed to investigate microRNAs that play role in rapid growth of the breast muscles in modern broiler chickens.

RESULTS: In this study, differential abundance of microRNA (miRNA) was analyzed in breast muscle of PeM and BPR chickens and the results were integrated with differentially expressed (DE) mRNA in the same tissues. A total of 994 miRNA were identified in PeM and BPR chicken lines from the initial analysis of small RNA sequencing data. After filtering and statistical analyses, the results showed miR-2131-5p, miR-221-5p, miR-126-3p, miR-146b-5p, miR-10a-5p, let-7b, miR-125b-5p, and miR-146c-5p up-regulated whereas miR-206 down-regulated in PeM compared to BPR breast muscle. Based on inhibitory regulations of miRNAs on the mRNA abundance, our computational analysis using miRDB, an online software, predicated that 118 down-regulated mRNAs may be targeted by the up-regulated miRNAs, while 35 up-regulated mRNAs appear to be due to a down-regulated miRNA (i.e., miR-206). Functional network analyses of target genes of DE miRNAs showed their involvement in calcium signaling, axonal guidance signaling, and NRF2-mediated oxidative stress response pathways suggesting their involvement in breast muscle growth in chickens.

CONCLUSION: From the integrated analyses of differentially expressed miRNA-mRNA data, we were able to identify breast muscle specific miRNAs and their target genes whose concerted actions can contribute to rapid growth and higher feed efficiency in modern broiler chickens. This study provides foundation data for elucidating molecular mechanisms that govern muscle growth in chickens.}, } @article {pmid30223793, year = {2018}, author = {Ballester, M and Amills, M and González-Rodríguez, O and Cardoso, TF and Pascual, M and González-Prendes, R and Panella-Riera, N and Díaz, I and Tibau, J and Quintanilla, R}, title = {Role of AMPK signalling pathway during compensatory growth in pigs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {682}, pmid = {30223793}, issn = {1471-2164}, support = {AGL2013-48742-C2-1-R//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; AGL2013-48742-C2-2-R//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; SEV-2015-0533//Ministerio de Economía y Competitividad/ ; RYC-2013-12573//Ministerio de Economía y Competitividad/ ; fellowship from the CAPES Foundation-Coordination of Improvement of Higher Education//Ministry of Education of the Federal Government of Brazil/ ; FPU12/00860//Ministerio de Educación, Cultura y Deporte/ ; }, mesh = {AMP-Activated Protein Kinases/genetics/*metabolism ; Animal Feed/analysis ; Animals ; Fatty Acids, Unsaturated/analysis ; Female ; Food Deprivation ; Gene Expression Regulation ; Metabolic Networks and Pathways ; Muscle, Skeletal/*growth & development/metabolism ; Phenotype ; *Signal Transduction ; Subcutaneous Fat/growth & development ; Swine/genetics/growth & development/*physiology ; *Transcriptome ; }, abstract = {BACKGROUND: The molecular basis of compensatory growth in monogastric animals has not yet been fully explored. Herewith, in this study we aim to determine changes in the pig skeletal muscle transcriptome profile during compensatory growth following a feed restriction period. A RNA-Seq experiment was performed with a total of 24 females belonging to a Duroc commercial line. Half of the animals received either a restricted (RE) or ad libitum (AL) diet during the first fattening period (60-125 d of age). After that, all gilts were fed ad libitum for a further ~30 d until the age of ~155 d, when animals were slaughtered and samples of gluteus medius muscle were harvested to perform RNA-Seq analyses and intramuscular fat content determination.

RESULTS: During the period following food restriction, RE animals re-fed ad libitum displayed compensatory growth, showed better feed conversion rate and tended to deposit more subcutaneous fat than AL fed animals. Animals were slaughtered in the phase of accelerated growth, when RE animals had not completely compensated the performance of AL group, showing lower live and carcass weights. At intramuscular level, RE gilts showed a higher content of polyunsaturated fatty acids during the compensatory growth phase. The comparison of RE and AL expression profiles allowed the identification of 86 (ǀlog2Fold-Changeǀ > 1, padj < 0.05) differentially expressed (DE) genes. A functional categorization of these DE genes identified AMPK Signaling as the most significantly enriched canonical pathway. This kinase plays a key role in the maintenance of energy homeostasis as well as in the activation of autophagy. Among the DE genes identified as components of AMPK Signaling pathway, five out of six genes were downregulated in RE pigs.

CONCLUSIONS: Animals re-fed after a restriction period exhibited a less oxidative metabolic profile and catabolic processes in muscle than animals fed ad libitum. The downregulation of autophagy observed in the skeletal muscle of pigs undergoing compensatory growth may constitute a mechanism to increase muscle mass thus ensuring an accelerated growth rate. These results reveal that the downregulation of AMPK Signaling plays an important role in compensatory growth in pigs.}, } @article {pmid30223790, year = {2018}, author = {Valdes, ID and van den Berg, J and Haagsman, A and Escobar, N and Meis, JF and Hagen, F and Haas, PJ and Houbraken, J and Wösten, HAB and de Cock, H}, title = {Comparative genotyping and phenotyping of Aspergillus fumigatus isolates from humans, dogs and the environment.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {118}, pmid = {30223790}, issn = {1471-2180}, abstract = {BACKGROUND: Aspergillus fumigatus is a ubiquitous saprotrophic fungus and an opportunistic pathogen of humans and animals. Humans and animals can inhale hundreds of A. fumigatus spores daily. Normally this is harmless for humans, but in case of immunodeficiency, invasive pulmonary aspergillosis (IPA) can develop with a high mortality rate. A. fumigatus also causes non-invasive mycoses like sino-nasal aspergillosis (SNA) in dogs.

RESULTS: In this study we compared A. fumigatus isolates from humans with suspected IPA, dogs with SNA, and a set of environmental isolates. Phylogenetic inference based on calmodulin (CaM) and beta-tubulin (benA) sequences did not reveal A. fumigatus sub-groups linked to the origin of the isolates. Genotyping and microsatellite analysis showed that each dog was infected by one A. fumigatus genotype, whereas human patients had mixed infections. Azole resistance was determined by antifungal susceptibility testing and sequencing of the cyp51A gene. A total of 12 out of 29 human isolates and 1 out of 27 environmental isolates were azole resistant. Of the azole resistant strains, 11 human isolates showed TR34/L98H (n = 6) or TR46/Y121F/T289A (n = 5). Phenotypically, isolates from dogs were more variable in growth speed and morphology when compared to those isolated from human and the environment.

CONCLUSIONS: 1. A. fumigatus from dogs with SNA are phenotypically very diverse in contrast to their environmental and human counterparts. 2. Phenotypic variability can be induced during the chronic infection process in the sinus of the dogs. The basis of this heterogeneity might be due to genomic differences and/or epigenetic variations. 3. Differences in dogs is a could be a result of within-host adaption and might be triggered by environmental factors in the sinus, however this hypothesis still needs to be tested.}, } @article {pmid30223789, year = {2018}, author = {Spindel, JE and Dahlberg, J and Colgan, M and Hollingsworth, J and Sievert, J and Staggenborg, SH and Hutmacher, R and Jansson, C and Vogel, JP}, title = {Association mapping by aerial drone reveals 213 genetic associations for Sorghum bicolor biomass traits under drought.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {679}, pmid = {30223789}, issn = {1471-2164}, support = {14/CJ000/09/02//Advanced Research Projects Agency - Energy/ ; DE-AC02-05CH1123//Biological and Environmental Research/ ; AC05-76RL01830//Biological and Environmental Research/ ; }, mesh = {Acclimatization/genetics ; Biological Variation, Population ; *Biomass ; California ; *Droughts ; Gene Expression Regulation, Plant ; Genes, Plant/*genetics ; Genome, Plant ; *Genome-Wide Association Study ; Genotype ; Linkage Disequilibrium ; Phenotype ; Polymorphism, Single Nucleotide ; Sorghum/*genetics ; Stress, Physiological/*genetics ; }, abstract = {BACKGROUND: Sorghum bicolor is the fifth most commonly grown cereal worldwide and is remarkable for its drought and abiotic stress tolerance. For these reasons and the large size of biomass varieties, it has been proposed as a bioenergy crop. However, little is known about the genes underlying sorghum's abiotic stress tolerance and biomass yield.

RESULTS: To uncover the genetic basis of drought tolerance in sorghum at a genome-wide level, we undertook a high-density phenomics genome wide association study (GWAS) in which 648 diverse sorghum lines were phenotyped at two locations in California once per week by drone over the course of a growing season. Biomass, height, and leaf area were measured by drone for individual field plots, subjected to two drought treatments and a well-watered control. The resulting dataset of ~ 171,000 phenotypic data-points was analyzed along with 183,989 genotype by sequence markers to reveal 213 high-quality, replicated, and conserved GWAS associations.

CONCLUSIONS: The genomic intervals defined by the associations include many strong candidate genes, including those encoding heat shock proteins, antifreeze proteins, and other domains recognized as important to plant stress responses. The markers identified by our study can be used for marker assisted selection for drought tolerance and biomass. In addition, our results are a significant step toward identifying specific sorghum genes controlling drought tolerance and biomass yield.}, } @article {pmid30223788, year = {2018}, author = {Veron, V and Marandel, L and Liu, J and Vélez, EJ and Lepais, O and Panserat, S and Skiba, S and Seiliez, I}, title = {DNA methylation of the promoter region of bnip3 and bnip3l genes induced by metabolic programming.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {677}, pmid = {30223788}, issn = {1471-2164}, support = {652831//FP7 Research infrastructures (Aquaexcel2020)/ ; 288925//FP7 Food, Agriculture and Fisheries, Biotechnology ()/ ; }, mesh = {Animal Feed/adverse effects ; Animals ; Apoptosis Regulatory Proteins/*genetics ; CpG Islands ; *DNA Methylation ; *Epigenesis, Genetic ; Evolution, Molecular ; Fish Diseases/*genetics/metabolism ; Gene Expression Regulation, Developmental ; Hypoxia/genetics/metabolism/*veterinary ; Methionine/*deficiency ; Oncorhynchus mykiss/*genetics/growth & development ; Phylogeny ; Promoter Regions, Genetic/*genetics ; }, abstract = {BACKGROUND: Environmental changes of biotic or abiotic nature during critical periods of early development may exert a profound influence on physiological functions later in life. This process, named developmental programming can also be driven through parental nutrition. At molecular level, epigenetic modifications are the most likely candidate for persistent modulation of genes expression in later life.

RESULTS: In order to investigate epigenetic modifications induced by programming in rainbow trout, we focused on bnip3 and bnip3l paralogous genes known to be sensitive to environmental changes but also regulated by epigenetic modifications. Two specific stimuli were used: (i) early acute hypoxia applied at embryo stage and (ii) broodstock and fry methionine deficient diet, considering methionine as one of the main methyl-group donor needed for DNA methylation. We observed a programming effect of hypoxia with an increase of bnip3a and the four paralogs of bnip3l expression level in fry. In addition, parental methionine nutrition was correlated to bnip3a and bnip3lb1 expression showing evidence for early fry programming. We highlighted that both stimuli modified DNA methylation levels at some specific loci of bnip3a and bnip3lb1.

CONCLUSION: Overall, these data demonstrate that methionine level and hypoxia stimulus can be of critical importance in metabolic programming. Both stimuli affected DNA methylation of specific loci, among them, an interesting CpG site have been identified, namely - 884 bp site of bnip3a, and may be positively related with mRNA levels.}, } @article {pmid30223787, year = {2018}, author = {Zhou, W and Altman, RB}, title = {Data-driven human transcriptomic modules determined by independent component analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {327}, pmid = {30223787}, issn = {1471-2105}, support = {R24 GM061374/GM/NIGMS NIH HHS/United States ; R01 LM005652/LM/NLM NIH HHS/United States ; GM102365//National Institutes of Health/ ; LM05652//National Institutes of Health/ ; U01 GM061374/GM/NIGMS NIH HHS/United States ; R01 GM102365/GM/NIGMS NIH HHS/United States ; GM61374//National Institutes of Health/ ; }, mesh = {*Algorithms ; Arthritis, Rheumatoid/genetics/pathology ; DNA Fingerprinting ; Humans ; Leukemia/genetics/pathology ; Oligonucleotide Array Sequence Analysis ; Rhabdomyosarcoma/genetics/pathology ; *Transcriptome ; }, abstract = {BACKGROUND: Analyzing the human transcriptome is crucial in advancing precision medicine, and the plethora of over half a million human microarray samples in the Gene Expression Omnibus (GEO) has enabled us to better characterize biological processes at the molecular level. However, transcriptomic analysis is challenging because the data is inherently noisy and high-dimensional. Gene set analysis is currently widely used to alleviate the issue of high dimensionality, but the user-defined choice of gene sets can introduce biasness in results. In this paper, we advocate the use of a fixed set of transcriptomic modules for such analysis. We apply independent component analysis to the large collection of microarray data in GEO in order to discover reproducible transcriptomic modules that can be used as features for machine learning. We evaluate the usability of these modules across six studies, and demonstrate (1) their usage as features for sample classification, and also their robustness in dealing with small training sets, (2) their regularization of data when clustering samples and (3) the biological relevancy of differentially expressed features.

RESULTS: We identified 139 reproducible transcriptomic modules, which we term fundamental components (FCs). In studies with less than 50 samples, FC-space classification model outperformed their gene-space counterparts, with higher sensitivity (p < 0.01). The models also had higher accuracy and negative predictive value (p < 0.01) for small data sets (less than 30 samples). Additionally, we observed a reduction in batch effects when data is clustered in the FC-space. Finally, we found that differentially expressed FCs mapped to GO terms that were also identified via traditional gene-based approaches.

CONCLUSIONS: The 139 FCs provide biologically-relevant summarization of transcriptomic data, and their performance in low sample settings suggest that they should be employed in such studies in order to harness the data efficiently.}, } @article {pmid30223777, year = {2018}, author = {Capote, T and Barbosa, P and Usié, A and Ramos, AM and Inácio, V and Ordás, R and Gonçalves, S and Morais-Cecílio, L}, title = {ChIP-Seq reveals that QsMYB1 directly targets genes involved in lignin and suberin biosynthesis pathways in cork oak (Quercus suber).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {198}, pmid = {30223777}, issn = {1471-2229}, support = {SFRH/BD/69785/2010//Fundação para a Ciência e a Tecnologia/ ; SFRH/BD/85879/2012//Fundação para a Ciência e a Tecnologia/ ; UID/AGR/00115/2013//Fundação para a Ciência e a Tecnologia/ ; IF/01015/2013/CP1209/CT0001//Fundação para a Ciência e a Tecnologia/ ; ALT20-03-0145-FEDER-000020//European Regional Development Fund/ ; }, mesh = {Binding Sites ; Chromatin Immunoprecipitation ; Enzymes/genetics/metabolism ; Gene Expression Regulation, Plant ; Lignin/biosynthesis/*genetics ; Lipids/*genetics ; Plant Proteins/*genetics/metabolism ; Quercus/*genetics/metabolism ; Regulatory Sequences, Nucleic Acid ; Seeds/genetics ; Transcription Factors/*genetics/metabolism ; }, abstract = {BACKGROUND: Gene activity is largely controlled by transcriptional regulation through the action of transcription factors and other regulators. QsMYB1 is a member of the R2R3-MYB transcription factor family related to secondary growth, and in particular, with the cork development process. In order to identify the putative gene targets of QsMYB1 across the cork oak genome we developed a ChIP-Seq strategy.

RESULTS: Results provide direct evidence that QsMY1B targets genes encoding for enzymes involved in the lignin and suberin pathways as well as gene encoding for ABCG transporters and LTPs implicated in the transport of monomeric suberin units across the cellular membrane. These results highlight the role of QsMYB1 as a regulator of lignin and suberin biosynthesis, transport and assembly.

CONCLUSION: To our knowledge, this work constitutes the first ChIP-Seq experiment performed in cork oak, a non-model plant species with a long-life cycle, and these results will contribute to deepen the knowledge about the molecular mechanisms of cork formation and differentiation.}, } @article {pmid30223776, year = {2018}, author = {Hwang, LD and Gharahkhani, P and Breslin, PAS and Gordon, SD and Zhu, G and Martin, NG and Reed, DR and Wright, MJ}, title = {Bivariate genome-wide association analysis strengthens the role of bitter receptor clusters on chromosomes 7 and 12 in human bitter taste.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {678}, pmid = {30223776}, issn = {1471-2164}, support = {R01 DC002995/DC/NIDCD NIH HHS/United States ; DC02995//National Institute on Deafness and Other Communication Disorders/ ; DC004698//National Institute on Deafness and Other Communication Disorders/ ; 1031119//National Health and Medical Research Council/ ; DP0664638//Australian Research Council/ ; 241944//National Health and Medical Research Council/ ; DP1093900//Australian Research Council/ ; R29 DC002995/DC/NIDCD NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; *Chromosomes, Human, Pair 12 ; *Chromosomes, Human, Pair 7 ; Female ; Genetic Pleiotropy ; *Genome-Wide Association Study ; Genotype ; Humans ; Male ; Models, Genetic ; *Multigene Family ; Polymorphism, Single Nucleotide ; Receptors, G-Protein-Coupled/genetics ; Taste Buds/metabolism ; Taste Perception/*genetics ; Young Adult ; }, abstract = {BACKGROUND: Human perception of bitter substances is partially genetically determined. Previously we discovered a single nucleotide polymorphism (SNP) within the cluster of bitter taste receptor genes on chromosome 12 that accounts for 5.8% of the variance in the perceived intensity rating of quinine, and we strengthened the classic association between TAS2R38 genotype and the bitterness of propylthiouracil (PROP). Here we performed a genome-wide association study (GWAS) using a 40% larger sample (n = 1999) together with a bivariate approach to detect previously unidentified common variants with small effects on bitter perception.

RESULTS: We identified two signals, both with small effects (< 2%), within the bitter taste receptor clusters on chromosomes 7 and 12, which influence the perceived bitterness of denatonium benzoate and sucrose octaacetate respectively. We also provided the first independent replication for an association of caffeine bitterness on chromosome 12. Furthermore, we provided evidence for pleiotropic effects on quinine, caffeine, sucrose octaacetate and denatonium benzoate for the three SNPs on chromosome 12 and the functional importance of the SNPs for denatonium benzoate bitterness.

CONCLUSIONS: These findings provide new insights into the genetic architecture of bitter taste and offer a useful starting point for determining the biological pathways linking perception of bitter substances.}, } @article {pmid30223774, year = {2018}, author = {Yang, CK and Huang, BH and Ho, SW and Huang, MY and Wang, JC and Gao, J and Liao, PC}, title = {Molecular genetic and biochemical evidence for adaptive evolution of leaf abaxial epicuticular wax crystals in the genus Lithocarpus (Fagaceae).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {196}, pmid = {30223774}, issn = {1471-2229}, support = {MOST 105-2628-B-003 -002 -MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Adaptation, Biological/genetics/*physiology ; Evolution, Molecular ; Fagaceae/genetics/*physiology/ultrastructure ; Hydroxybenzoates/metabolism ; Microscopy, Electron, Scanning ; Phylogeny ; Plant Leaves/*chemistry/genetics/metabolism ; Plant Proteins/*genetics ; Secondary Metabolism ; Selection, Genetic ; Waxes/*chemistry ; }, abstract = {BACKGROUND: Leaf epicuticular wax is an important functional trait for physiological regulation and pathogen defense. This study tests how selective pressure may have forced the trait of leaf abaxial epicuticular wax crystals (LAEWC) and whether the presence/absence of LAEWC is associated with other ecophysiological traits. Scanning Electron Microscopy was conducted to check for LAEWC in different Lithocarpus species. Four wax biosynthesis related genes, including two wax backbone genes ECERIFERUM 1 (CER1) and CER3, one regulatory gene CER7 and one transport gene CER5, were cloned and sequenced. Ecophysiological measurements of secondary metabolites, photosynthesis, water usage efficiency, and nutrition indices were also determined. Evolutionary hypotheses of leaf wax character transition associated with the evolution of those ecophysiological traits as well as species evolution were tested by maximum likelihood.

RESULTS: Eight of 14 studied Lithocarpus species have obvious LAEWC appearing with various types of trichomes. Measurements of ecophysiological traits show no direct correlations with the presence/absence of LAEWC. However, the content of phenolic acids is significantly associated with the gene evolution of the wax biosynthetic backbone gene CER1, which was detected to be positively selected when LAEWC was gained during the late-Miocene-to-Pliocene period.

CONCLUSIONS: Changes of landmass and vegetation type accelerated the diversification of tropical and subtropical forest trees and certain herbivores during the late Miocene. As phenolic acids were long thought to be associated with defense against herbivories, co-occurrence of LAEWC and phenolic acids may suggest that LAEWC might be an adaptive defensive mechanism in Lithocarpus.}, } @article {pmid30223770, year = {2018}, author = {Yu, C and Luo, X and Zhan, X and Hao, J and Zhang, L and L Song, YB and Shen, C and Dong, M}, title = {Comparative metabolomics reveals the metabolic variations between two endangered Taxus species (T. fuana and T. yunnanensis) in the Himalayas.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {197}, pmid = {30223770}, issn = {1471-2229}, support = {2016YFC0503100//National Key R&D Program of China/ ; 31501810//National Natural Science Foundation of China/ ; 31601343//National Natural Science Foundation of China/ ; LQ14C060001//Zhejiang Provincial Natural Science Foundation of China/ ; }, mesh = {Endangered Species ; Flavonoids/metabolism ; Metabolomics/*methods ; Paclitaxel/metabolism ; Secondary Metabolism ; Taxoids/analysis/metabolism ; Taxus/*metabolism ; Tibet ; }, abstract = {BACKGROUND: Plants of the genus Taxus have attracted much attention owing to the natural product taxol, a successful anti-cancer drug. T. fuana and T. yunnanensis are two endangered Taxus species mainly distributed in the Himalayas. In our study, an untargeted metabolomics approach integrated with a targeted UPLC-MS/MS method was applied to examine the metabolic variations between these two Taxus species growing in different environments.

RESULTS: The level of taxol in T. yunnanensis is much higher than that in T. fuana, indicating a higher economic value of T. yunnanensis for taxol production. A series of specific metabolites, including precursors, intermediates, competitors of taxol, were identified. All the identified intermediates are predominantly accumulated in T. yunnanensis than T. fuana, giving a reasonable explanation for the higher accumulation of taxol in T. yunnanensis. Taxusin and its analogues are highly accumulated in T. fuana, which may consume limited intermediates and block the metabolic flow towards taxol. The contents of total flavonoids and a majority of tested individual flavonoids are significantly accumulated in T. fuana than T. yunnanensis, indicating a stronger environmental adaptiveness of T. fuana.

CONCLUSIONS: Systemic metabolic profiling may provide valuable information for the comprehensive industrial utilization of the germplasm resources of these two endangered Taxus species growing in different environments.}, } @article {pmid30223769, year = {2018}, author = {Simonsen, AT and Hansen, MC and Kjeldsen, E and Møller, PL and Hindkjær, JJ and Hokland, P and Aggerholm, A}, title = {Systematic evaluation of signal-to-noise ratio in variant detection from single cell genome multiple displacement amplification and exome sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {681}, pmid = {30223769}, issn = {1471-2164}, mesh = {Alleles ; Allelic Imbalance ; Cell Count ; Cell Line, Tumor ; Cytogenetic Analysis ; DNA Copy Number Variations ; *Genetic Variation ; Genome, Human/*genetics ; *Genomics ; Humans ; *Signal-To-Noise Ratio ; *Single-Cell Analysis ; Whole Exome Sequencing ; }, abstract = {BACKGROUND: The current literature on single cell genomic analyses on the DNA level is conflicting regarding requirements for cell quality, amplification success rates, allelic dropouts and resolution, lacking a systematic comparison of multiple cell input down to the single cell. We hypothesized that such a correlation assay would provide an approach to address the latter issues, utilizing the leukemic cell line OCI-AML3 with a known set of genetic aberrations.

RESULTS: By analyzing single and multiple cell replicates (2 to 50 cells) purified by micromanipulation and serial dilution we stringently assessed the signal-to-noise ratio (SNR) from single as well as a discrete number of cells based on a multiple displacement amplification method, with whole exome sequencing as signal readout. In this setting, known OCI-AML3 mutations as well as large copy number alterations could be identified, adding to the current knowledge of cytogenetic status. The presence of DNMT3A R882C, NPM1 W288 fs and NRAS Q61L was consistent, in spite of uneven allelic read depths. In contrast, at the level of single cells, we observed that one-third to half of all variants were not reproduced in the replicate sample, and this allelic mismatch displayed an exponential function of cell input. Large signature duplications were discernible from 5 cells, whereas deletions were visible down to the single cell. Thus, even under highly optimized conditions, single cell whole genome amplification and interpretation must be taken with considerable caution, given that allelic change is frequent and displays low SNR. Allelic noise is rapidly alleviated with increased cell input, and the SNR is doubled from 2 to 50 cells.

CONCLUSIONS: In conclusion, we demonstrate noisy allele distributions, when analyzing genetic aberrations within single cells relative to multiple cells. Based on the presented data we recommend that single cell analyses should include replicate cell dilution assays for a given setup for relative assessment of procedure-specific SNR to ensure that the resolution supports the specific hypotheses.}, } @article {pmid30223767, year = {2018}, author = {Zheng, W and Lin, H and Liu, X and Xu, B}, title = {A document level neural model integrated domain knowledge for chemical-induced disease relations.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {328}, pmid = {30223767}, issn = {1471-2105}, support = {No.61572102//National Natural Science Foundation of China/ ; No.61572098//National Natural Science Foundation of China/ ; No.61502071//National Natural Science Foundation of China/ ; No2016YFC0901900//Major State Research Development Program of China/ ; No.DUT16RC(4)63//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Data Mining ; Databases, Factual ; *Disease ; Humans ; Machine Learning ; *Neural Networks (Computer) ; }, abstract = {BACKGROUND: The effective combination of texts and knowledge may improve performances of natural language processing tasks. For the recognition of chemical-induced disease (CID) relations which may span sentence boundaries in an article, although existing CID systems explored the utilization for knowledge bases, the effects of different knowledge on the identification of a special CID haven't been distinguished by these systems. Moreover, systems based on neural network only constructed sentence or mention level models.

RESULTS: In this work, we proposed an effective document level neural model integrated domain knowledge to extract CID relations from biomedical articles. Basic semantic information of an article with respect to a special CID candidate pair was learned from the document level sub-network module. Furthermore, knowledge attention depending on the representation of the article was proposed to distinguish the influences of different knowledge on the special CID pair and then the final representation of knowledge was formed by aggregating weighed knowledge. Finally, the integrated representations of texts and knowledge were passed to a softmax classifier to perform the CID recognition. Experimental results on the chemical-disease relation corpus proposed by BioCreative V show that our proposed system integrated knowledge achieves a good overall performance compared with other state-of-the-art systems.

CONCLUSIONS: Experimental analyses demonstrate that the introduced attention mechanism on domain knowledge plays a significant role in distinguishing influences of different knowledge on the judgment for a special CID relation.}, } @article {pmid30223033, year = {2018}, author = {Pos, KM}, title = {Bacterial efflux transporters in the limelight.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {349-350}, doi = {10.1016/j.resmic.2018.09.001}, pmid = {30223033}, issn = {1769-7123}, mesh = {Bacteria/genetics/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Membrane Transport Proteins/genetics/*metabolism ; }, } @article {pmid30222957, year = {2018}, author = {Ferguson, JW and Devarajan, M and Atit, RP}, title = {Stage-specific roles of Ezh2 and Retinoic acid signaling ensure calvarial bone lineage commitment.}, journal = {Developmental biology}, volume = {443}, number = {2}, pages = {173-187}, pmid = {30222957}, issn = {1095-564X}, support = {R01 DE018470/DE/NIDCR NIH HHS/United States ; S10 OD016164/OD/NIH HHS/United States ; T32 AR007505/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Enhancer of Zeste Homolog 2 Protein/*metabolism/physiology ; Gene Expression Regulation, Developmental/genetics ; Gestational Age ; Mesoderm/embryology/metabolism ; Mice ; Neural Crest/embryology/metabolism ; Signal Transduction ; Skull/*embryology/metabolism ; Tretinoin/*metabolism/physiology ; }, abstract = {Development of the skull bones requires the coordination of two stem progenitor populations, the cranial neural crest cells (CNCC) and head paraxial mesoderm (PM), to ensure cell fate selection and morphogenesis. The epigenetic methyltransferase, Ezh2, plays a role in skull bone formation, but the spatiotemporal function of Ezh2 between the CNCC- and PM-derived bone formation in vivo remains undefined. Here, using a temporally-inducible conditional deletion of Ezh2 in both the CNCC- and PM- derived cranial mesenchyme between E8.5 and E9.5, we find a reduction of the CNCC-derived calvarial bones and a near complete loss of the PM-derived calvarial bones due to an arrest in calvarial bone fate commitment. In contrast, deletion of Ezh2 after E9.5 permits PM-derived skull bone development, suggesting that Ezh2 is required early to guide calvarial bone progenitor commitment. Furthermore, exposure to all-trans Retinoic acid at E10.0 can mimic the Ezh2 mutant calvarial phenotype, and administration of the pan retinoic acid receptor (RAR) antagonist, BMS-453, to Ezh2 mutants partially restores the commitment to the calvarial bone lineage and PM-derived bone development in vivo. Exogenous RA signaling activation in the Ezh2 mutants leads to synergistic activation of the anti-osteogenic factors in the cranial mesenchyme in vivo. Thus, RA signaling and EZH2 can function in parallel to guide calvarial bone progenitor commitment by balancing the suppression of anti-osteogenic factors.}, } @article {pmid30222229, year = {2018}, author = {Belkina, EG and Naimark, EB and Gorshkova, AA and Markov, AV}, title = {Does adaptation to different diets result in assortative mating? Ambiguous results from experiments on Drosophila.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1803-1814}, doi = {10.1111/jeb.13375}, pmid = {30222229}, issn = {1420-9101}, support = {18-04-00915//Russian Foundation for Fundamental Research/ ; }, abstract = {The emergence of behavioural isolation between populations under divergent selection can be crucial for ecological speciation, but the mechanisms underlying such isolation are poorly understood. Several experimental evolution studies have shown that positive assortative mating (preference for similar mates) can arise rapidly in Drosophila laboratory populations reared in different stressful conditions, while other studies failed to confirm this effect. Here, we present the results of an evolution experiment in which outbred lines of Drosophila melanogaster were reared for 1-2 years on one of the three different diets (standard, starch based or high salt). We show that nonrandom mating arose in some, but not all lines, and that the manifestations and possible interpretations of this nonrandomness depend strongly on the type of tests used to assess mating preferences. More specifically, multiple-choice four-fly tests revealed positive assortative mating (prevalence of homogamic matings) in some starch-adapted and salt-adapted lines when paired with a control line reared on the standard diet, but competitive three-fly tests rather revealed competitive advantage of control males and females over the flies reared on stressful diets. The results imply that divergent adaptation can result in differences in mating propensity or competitive ability, which, in turn, may either facilitate or hamper speciation depending on the relative frequency of high- vs. low-competition settings in natural habitats of the diverging populations. The results also emphasize the importance of using diverse tests for assessing mating structure in natural and laboratory populations.}, } @article {pmid30222099, year = {2018}, author = {Najar, IN and Sherpa, MT and Das, S and Verma, K and Dubey, VK and Thakur, N}, title = {Geobacillus yumthangensis sp. nov., a thermophilic bacterium isolated from a north-east Indian hot spring.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3430-3434}, doi = {10.1099/ijsem.0.003002}, pmid = {30222099}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geobacillus/*classification/genetics/isolation & purification ; Hot Springs/*microbiology ; India ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A thermophilic, spore-forming, rod-shaped bacterium isolated from the Yumthang hot spring in North Sikkim, India was subjected to taxonomic studies. The thermophilic bacterial isolate was designated as strain AYN2T. Cells were Gram-stain-positive, aerobic, motile, rod-shaped, catalase-positive and methyl red-negative. Strain AYN2T was able to grow in the pH range from 6 to 10 (optimum, pH 7.5-8.0), at 40-70 °C (60 °C) and in NaCl concentrations of 0-4 % (1 %). The major cellular fatty acids were iso-C15 : 0 (12.8 %), iso-C16 : 0 (13.9 %) and iso-C17 : 0 (13.8 %). No matches were found in the rtsba6 Sherlock libraries. The G+C content of the genomic DNA was 42.11 mol%. Based on phylogenetic analysis of the 16S rRNA gene sequences, strain AYNT showed highest sequence similarity to the type strain of Geobacillus toebii (96 %). However, the phenotypic properties of strain AYN2T were clearly distinct from those of G. toebii and related species. On the basis of polyphasic analysis, strain AYN2T represents a novel species in the genus Geobacillus, for which the name Geobacillus yumthangensis sp. nov. is proposed. The type strain is AYN2T(MTCC=12749=KCTC=33950= JCM 32596).}, } @article {pmid30222097, year = {2018}, author = {Wang, JJ and Chen, Q and Li, YZ}, title = {Chryseolinea flava sp. nov., a new species of Chryseolinea isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3518-3522}, doi = {10.1099/ijsem.0.003022}, pmid = {30222097}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A pale yellow bacterial strain, designated SDU1-6T, was isolated from a soil sample collected in the Jinan campus of Shandong University, Shandong Province, PR China. The strain was aerobic, motile, Gram-stain-negative and rod-shaped. Cellular growth occurred at 13-37 °C, pH 5.0-10.0 and with 0-0.1 % (w/v) NaCl, and the optimal growth was at 25 °C and pH 7.5. SDU1-6T had the highest 16S rRNA gene similarity of 95.42 % with Chryseolinea serpens DSM 24574T. The genome was 6 542 746 bp in length with 43.5 mol% DNA G+C content. The major fatty acids of SDU1-6T were C16 : 1ω5 and iso-C15 : 0, the major menaquinone was menaquinone-7 (MK-7) and the major polar lipid was phosphatidylethanolamine. On the basis of the polyphasic evidence and the 16S rRNA gene sequence, SDU1-6T represents a novel species of the genus Chryseolinea, for which the name Chryseolineaflava sp. nov. is proposed. The type strain is SDU1-6T (=CGMCC 1.13492T=JCM 32520T).}, } @article {pmid30222096, year = {2018}, author = {Ji, X and Zhang, C and Zhang, X and Xu, Z and Ding, Y and Zhang, Y and Song, Q and Li, B and Zhao, H}, title = {Pelagivirga sediminicola gen. nov., sp. nov. isolated from the Bohai Sea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3494-3499}, doi = {10.1099/ijsem.0.003015}, pmid = {30222096}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Oceans and Seas ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative bacterium, strain BH-SD19T, that was isolated from a marine sediment sample collected from the Bohai Sea, was subjected to a polyphasic taxonomic study. Cells of BH-SD19T are non-flagellated, non-gliding, oval-shaped rods, 0.5-1.0 µm wide and 1.0-2.0 µm long. BH-SD19T is strictly aerobic, and oxidase- and catalase-positive. Growth occurs at 15-40 °C (optimum 35 °C), at pH 6.0-8.5 (optimum 7.0-7.5) and with 1-10 % (w/v) NaCl (optimum 2 %). The predominant fatty acids are C19 : 0cyclo ω8c (46.5 %), C16 : 0 (20.3 %) and C18 : 1ω7c and/or C18 : 1ω6c (10.6 %). The major respiratory quinone is Q-10. The major polar lipids are phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The DNA G+C content is 64.0 mol%. BH-SD19T shows the highest 16S rRNA sequence similarity to Pontibaca methylaminivorans (95.2 %) and strains of species of the genus Roseovarius(93.4-95.2 %). Sequence similarity values between BH-SD19T and other phylogenetically related species are all below 95.0 %. Phylogenetic trees based on 16S rRNA gene sequences indicate that BH-SD19T forms a distinct lineage and does not join any known genera in the trees. Phenotypic, chemotaxonomic and phylogenetic data indicate that BH-SD19T represents a novel genus and species in the family Rhodobacteraceae, for which the name Pelagivirga sediminicola gen. nov., sp. nov. is proposed. The type strain is BH-SD19T (=CCTCC AB 2017074T=KCTC 62202T).}, } @article {pmid30222095, year = {2018}, author = {Lee, DW and Lee, H and Kwon, BO and Khim, JS and Yim, UH and Park, H and Park, B and Choi, IG and Kim, BS and Kim, JJ}, title = {Maribacter litoralis sp. nov. a marine bacterium isolated from seashore.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3471-3478}, doi = {10.1099/ijsem.0.003011}, pmid = {30222095}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-negative, moderately halophilic and aerobic bacterium, designated strain SDRB-Phe2T, was isolated from coastal sediment of the yellow sea in Sindu-ri, Republic of Korea. Cells were oxidase-positive, catalase-positive, rod-shaped and surrounded by a capsule with gliding motility. Colonies were yellow-coloured, circular, pulvinate with entire margins. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SDRB-Phe2T formed a distinct lineage within the genus Maribacter of the family Flavobacteriaceae. Stain SDRB-Phe2T exhibited 16S rRNA gene sequence similarity values of 97.1-98.9 % to the type strains of Maribacterstanieri, Maribacterspongiicola, Maribacter forsetii, Maribacter dokdonensis, Maribacter aquivivus, Maribactercaenipelagi, Maribacterlitorisediminis, Maribactersedimenticola, Maribacterulvicola, Maribacter confluentis and Maribacter orientalis, and of 94.8-96.7 % to the type strains of the other species of the genus Maribacter. Strain SDRB-Phe2T contained MK-6 as the predominant respiratory quinone and iso-C15 : 1 G, iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) as the major fatty acids. The polar lipids of strain SDRB-Phe2T were phosphatidylethanolamine, one unidentified amino lipid and two unidentified lipids. The DNA G+C content was 36.2 mol%. DNA-DNA relatedness values of strain SDRB-Phe2T to the type strains of the 11 phylogenetically related species of the genus Maribacter were 21.9-38.6 %. On the basis of the phenotypic features, phylogenetic and DNA-DNA hybridization analyses presented here, strain SDRB-Phe2T (=JCM 32373T=KCTC 62273T=DSM 106042T) represents a novel species of the genus Maribacter, for which the name Maribacterlitoralis sp. nov. is proposed.}, } @article {pmid30222094, year = {2018}, author = {Luo, HR and Chen, ZY and Fei, JJ and Du, ZJ}, title = {Brumimicrobium salinarum sp. nov., isolated from a marine solar saltern.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3447-3451}, doi = {10.1099/ijsem.0.003003}, pmid = {30222094}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Glycolipids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A Gram-stain-negative, aerobic, rod-shaped and orange-coloured strain, designated LHR20T, was isolated from a marine solar saltern. The novel strain LHR20T was able to grow at 15-40 °C (optimum 33-37 °C), at pH 6.5-9.5 (optimum pH 7.5-8.0) and with 2.0-11.0 % (w/v) NaCl (optimum 4.0-5.0 %). MK-6 was the sole respiratory quinone, and the major fatty acids were iso-C15 : 0 and iso-C17 : 0 3-OH. The predominant polar lipids of strain LHR20T were phosphatidylethanolamine (PE), aminolipid (AL), glycolipid (GL1) and two unidentified lipids (L1, L2). The genomic DNA G+C content was 35.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain LHR20T was a member of the genus Brumimicrobium and its closest relative was Brumimicrobium mesophilum JCM 14063T (97.5 % sequence similarity). The average nucleotide identity value between strain LHR20T and B. mesophilum JCM 14063T was 73.7 %. This evidence from phenotypic, chemotaxonomic and phylogenetic analyses suggests that strain LHR20T represents a novel species of the genus Brumimicrobium. Therefore, the name Brumimicrobium salinarum sp. nov. is proposed. The type strain is LHR20T (=KCTC 62372T=MCCC 1H00247T).}, } @article {pmid30222093, year = {2018}, author = {Yi, KJ and Im, WT and Kim, DW and Kim, SK}, title = {Ottowia konkukae sp. nov., isolated from rotten biji (tofu residue).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3458-3462}, doi = {10.1099/ijsem.0.003009}, pmid = {30222093}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Comamonadaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Food Microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Soy Foods/*microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative, aerobic, non-motile, non-spore-forming and rod-shaped bacterial strain, designated SK3863T, was isolated from rotten biji (residue remaining after making tofu). This bacterium was characterized in order to determine its taxonomic position by using the polyphasic approach. Strain SK3863T grew well at 25-37 °C on Reasoner's 2A agar plates. On the basis of 16S rRNA gene sequence similarity, strain SK3863T belonged to the family Comamonadaceae and was related to Ottowia beijingensis GCS-AN-3T (96.5 % sequence similarity) and Ottowia pentelensis RB3-7T (96.4 %). Lower sequence similarities (96.2 %) were found to all of the other recognized members of the genus Ottowia. The G+C content of the genomic DNA was 65.8 mol%. The major respiratory lipoquinone was ubiquinone 8 and the major fatty acids were C16 : 1ω6c/C16 : 1ω7c, C16 : 0 and C18 : 1ω7c/C18 : 1ω6c. Strain SK3863T could be differentiated genotypically and phenotypically from the recognized species of the genus Ottowia. The isolate therefore represents a novel species, for which the name Ottowia konkukae sp. nov. is proposed, with the type strain SK3863T (=KCCM 43236T=DSM 105395T).}, } @article {pmid30221814, year = {2018}, author = {March, LE and Smaby, RM and Setton, EVW and Sharma, PP}, title = {The evolution of selector gene function: Expression dynamics and regulatory interactions of tiptop/teashirt across Arthropoda.}, journal = {Evolution & development}, volume = {20}, number = {6}, pages = {219-232}, doi = {10.1111/ede.12270}, pmid = {30221814}, issn = {1525-142X}, mesh = {Amino Acid Sequence ; Animals ; Arthropod Proteins/chemistry/*genetics ; Arthropods/classification/*genetics ; *Evolution, Molecular ; Female ; Male ; Repressor Proteins/chemistry/*genetics ; Transcription Factors/chemistry/*genetics ; }, abstract = {The transcription factors spineless (ss) and tiptop/teashirt (tio/tsh) have been shown to be selectors of distal appendage identity in an insect, but it is unknown how they regulate one another. Here, we examined the regulatory relationships between these two determinants in the milkweed bug Oncopeltus faciatus, using maternal RNA interference (RNAi). We show that Ofas-ss RNAi embryos bear distally transformed antennal buds with heterogeneous Ofas-tio/tsh expression domains comparable to wild type legs. In the reciprocal experiment, Ofas-tio/tsh RNAi embryos bear distally transformed walking limb buds with ectopic expression of Ofas-ss in the distal leg primordia. These data suggest that Ofas-ss is required for the maintenance of Ofas-tio/tsh expression in the distal antenna, whereas Ofas-tio/tsh represses Ofas-ss in the leg primordia. To assess whether expression boundaries of tio/tsh are associated with the trunk region more generally, we surveyed the expression of one myriapod and two chelicerate tio/tsh homologs. Our expression survey suggests that tio/tsh could play a role in specifying distal appendage identity across Arthropoda, but Hox regulation of tio/tsh homologs has been evolutionarily labile.}, } @article {pmid30221481, year = {2018}, author = {Takahashi, KH and Ishimori, M and Iwata, H}, title = {HSP90 as a global genetic modifier for male genital morphology in Drosophila melanogaster.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2419-2434}, doi = {10.1111/evo.13598}, pmid = {30221481}, issn = {1558-5646}, support = {JP17H05014//Ryobi Teien Memory Foundation and JSPS KAKENHI/ ; }, abstract = {The molecular chaperone protein HSP90 has been proposed to modulate genotype-phenotype relationship in a broad range of organisms. We explore the proposed genetic modifier effect of HSP90 through a genomewide analysis. Here, we show that HSP90 functions as a genetic modifier of genital morphology in Drosophila melanogaster. We identified a large number of single-nucleotide polymorphisms (SNPs) with an HSP90-dependent effect by using genome wide association analysis. We classified the SNPs into the ones under capacitance effect (smaller allelic effect under HSP90 inhibition) or the ones under potentiation effect (larger allelic effect under HSP90 inhibition). Although the majority of SNPs are under capacitance, there are a large number of SNPs under potentiation. This observation provides support for a model in which Hsp90 is not described exclusively as a "genetic capacitor," but is described more broadly as a "genetic modifier." Because the majority of the candidate genes estimated from SNPs with an HSP90-dependent effect in the current study has never been reported to interact with HSP90 directly, the global genetic modifier effect of HSP90 may be exhibited through epistatic interactions in gene regulatory networks.}, } @article {pmid30221442, year = {2018}, author = {Schoelmerich, MC and Katsyv, A and Sung, W and Mijic, V and Wiechmann, A and Kottenhahn, P and Baker, J and Minton, NP and Müller, V}, title = {Regulation of lactate metabolism in the acetogenic bacterium Acetobacterium woodii.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4587-4595}, doi = {10.1111/1462-2920.14412}, pmid = {30221442}, issn = {1462-2920}, support = {//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Acetogenic bacteria compete in an energy-limited environment by coupling different metabolic routes to their central metabolism of CO2 fixation. The underlying regulatory mechanisms are often still not understood. In this work, we analysed how lactate metabolism is regulated in the model acetogen Acetobacterium woodii. Construction of a ΔlctCDEF mutant and growth analyses demonstrated that the genes are essential for growth on lactate. Subsequent bridging PCR and quantitative PCR analyses revealed that the lctBCDEF genes form an operon that was expressed only during lactate metabolism. The lctA gene was cloned, expressed in Escherichia coli and purified. LctA bound to the intergenic DNA region between lctA and the lct operon in electromobility shift assays, and binding was revoked in the presence of lactate. Further restriction site protection analyses consolidated the lactate-dependent binding of LctA and identified the binding site within the DNA. Cells grew mixotrophically on lactate and another energy source and showed no diauxic growth. From these data, we conclude that the catabolic lactate metabolism is encoded by the lct operon and its expression is negatively regulated by the DNA-binding repressor LctA.}, } @article {pmid30221347, year = {2018}, author = {Han, CS and Tuni, C and Ulcik, J and Dingemanse, NJ}, title = {Increased developmental density decreases the magnitude of indirect genetic effects expressed during agonistic interactions in an insect.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2435-2448}, doi = {10.1111/evo.13600}, pmid = {30221347}, issn = {1558-5646}, support = {//BioNa Junior Scientist Award of the LMU/ ; FP7-MC-IIF//FP7 People: Marie-Curie Actions/ ; 624672//FP7 People: Marie-Curie Actions/ ; NRF-2017R1A6A3A04002489//National Research Foundation of Korea/ ; }, abstract = {The expression of aggression depends not only on the direct genetic effects (DGEs) of an individual's genes on its own behavior, but also on indirect genetic effects (IGEs) caused by heritable phenotypes expressed by social partners. IGEs can affect the amount of heritable variance on which selection can act. Despite the important roles of IGEs in the evolutionary process, it remains largely unknown whether the strength of IGEs varies across life stages or competitive regimes. Based on manipulations of nymphal densities and > 3000 pair-wise aggression tests across multiple life stages, we experimentally demonstrate that IGEs on aggression are stronger in field crickets (Gryllus bimaculatus) that develop at lower densities than in those that develop at higher densities, and that these effects persist with age. The existence of density-dependent IGEs implies that social interactions strongly determine the plastic expression of aggression when competition for resources is relaxed. A more competitive (higher density) rearing environment may fail to provide crickets with sufficient resources to develop social cognition required for strong IGEs. The contribution of IGEs to evolutionary responses was greater at lower densities. Our study thereby demonstrates the importance of considering IGEs in density-dependent ecological and evolutionary processes.}, } @article {pmid30220992, year = {2018}, author = {Ghosal, R and Eichmiller, JJ and Witthuhn, BA and Sorensen, PW}, title = {Attracting Common Carp to a bait site with food reveals strong positive relationships between fish density, feeding activity, environmental DNA, and sex pheromone release that could be used in invasive fish management.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6714-6727}, pmid = {30220992}, issn = {2045-7758}, abstract = {Measurement of environmental DNA (eDNA) is becoming a common technique to survey for rare and invasive fish due to its sensitivity and specificity. However, its utility is limited by an incomplete understanding of factors governing its sources and fates. Failure to detect eDNA is especially difficult to interpret so surveillance techniques often collect large numbers of samples across broad regions. If, however, fish could be reliably attracted to a single location where their eDNA could be easily measured that would be useful. We conducted a proof-of-concept study of this idea using invasive Common Carp. We monitored the distribution of radio-tagged Carp and their eDNA across a 67 ha lake focusing at the bait site while a pheromone (Prostaglandin F2α; PGF 2α) was also measured to determine their reproductive condition. Prior to baiting, Carp were patchily distributed and while eDNA was occasionally detectable, it was patchy and only loosely associated with moderately dense groups of fish. Further, neither Carp, nor their eDNA were consistently measurable at the bait site and surrounding region, and the pheromone was not measurable at all. However, once baiting commenced, Carp started visiting the bait site and feeding, especially at night, where eDNA levels increased 500-fold as fish densities doubled and PGF 2α became detectable. Fish presence, eDNA and pheromone concentrations peaked at night after 6 days, strongly suggesting feeding activity was the main driver. While the presence of eDNA precisely coincided with this aggregation, levels had dropped dramatically within 5 m. PGF 2α levels dropped less rapidly and demonstrated the presence of live mature fish. We suggest that food could be used to train fish to come to locations where they otherwise are too scarce to be reliably measured, increasing their eDNA release, making them measurable, and their reproductive condition also discernable by measuring pheromones.}, } @article {pmid30220757, year = {2018}, author = {Guiaşu, RC and Tindale, CW}, title = {Logical fallacies and invasion biology.}, journal = {Biology & philosophy}, volume = {33}, number = {5}, pages = {34}, pmid = {30220757}, issn = {0169-3867}, abstract = {Leading invasion biologists sometimes dismiss critics and criticisms of their field by invoking "the straw man" fallacy. Critics of invasion biology are also labelled as a small group of "naysayers" or "contrarians", who are sometimes engaging in "science denialism". Such unfortunate labels can be seen as a way to possibly suppress legitimate debates and dismiss or minimize reasonable concerns about some aspects of invasion biology, including the uncertainties about the geographic origins and complex environmental impacts of species, and the control programs against species perceived as "invasive". In assessing the quality of the debate in this area, we examine the validity of the use of various strategies, including the "straw man" concept, and explore a range of potential logical fallacies present in some recent prominent discussions about invasion biology and so-called "invasive" species. The goal is to add some clarity to the concepts involved, point out some problematic issues, and improve the quality of the debates as the discussions move forward.}, } @article {pmid30220472, year = {2018}, author = {Torkamani, A}, title = {Drilling for Insight: Forecasting Phenotype from Genotype.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {11}, pages = {821-822}, doi = {10.1016/j.tig.2018.09.001}, pmid = {30220472}, issn = {0168-9525}, abstract = {The manifestation of disease can vary substantially from person to person. Yet, much of the emphasis of genomics in individualized medicine has been on linking genetic variants to broad disease categories. A new approach takes a first step towards predicting detailed phenotypic information from disease-causative variants.}, } @article {pmid30220471, year = {2018}, author = {O'Connor, PJ and Cargill, MA}, title = {Better Scientific Writing Does Not Need Linguistic Alchemy: Response to Doubleday and Connell 2017.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {813-814}, doi = {10.1016/j.tree.2018.08.009}, pmid = {30220471}, issn = {1872-8383}, } @article {pmid30220445, year = {2019}, author = {Watanabe, S and Shirogane, Y and Sato, Y and Hashiguchi, T and Yanagi, Y}, title = {New Insights into Measles Virus Brain Infections.}, journal = {Trends in microbiology}, volume = {27}, number = {2}, pages = {164-175}, doi = {10.1016/j.tim.2018.08.010}, pmid = {30220445}, issn = {1878-4380}, abstract = {Measles virus (MeV) may persist in the brain, causing fatal neurodegenerative diseases, subacute sclerosing panencephalitis, and measles inclusion-body encephalitis. However, the mechanism of MeV propagation in the brain remains unexplained because human neurons affected by the diseases do not express the known receptors for MeV. Recent studies have revealed that certain changes in the ectodomain of the MeV fusion (F) protein play a key role in MeV spread in the brain. These changes destabilize the prefusion form of the F protein and render it hyperfusogenic, which in turn allows the virus to propagate in neurons. Based on crystal structures of the F protein, effective fusion inhibitors could be developed to treat these diseases.}, } @article {pmid30219893, year = {2018}, author = {Zélé, F and Santos, JL and Godinho, DP and Magalhães, S}, title = {Wolbachia both aids and hampers the performance of spider mites on different host plants.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy187}, pmid = {30219893}, issn = {1574-6941}, abstract = {In the last few decades, many studies have revealed the potential role of arthropod bacterial endosymbionts in shaping the host range of generalist herbivores and their performance on different host plants, which, in turn, might affect endosymbiont distribution in herbivore populations. We tested this by measuring the prevalence of endosymbionts in natural populations of the generalist spider mite Tetranychus urticae on different host plants. Focusing on Wolbachia, we then analysed how symbionts affected mite life-history traits on the same host plants in the laboratory. Overall, the prevalences of Cardinium and Rickettsia were low, whereas that of Wolbachia was high, with the highest values on bean and eggplant and the lowest on morning glory, tomato and zuchini. Although most mite life-history traits were affected by the plant species only, Wolbachia infection was detrimental for the egg-hatching rate on morning glory and zucchini, and led to a more female-biased sex ratio on morning glory and eggplant. These results suggest that endosymbionts may affect the host range of polyphagous herbivores, both by aiding and hampering their performance, depending on the host plant and on the life-history trait that affects performance the most. Conversely, endosymbiont spread may be facilitated or hindered by the plants on which infected herbivores occur.}, } @article {pmid30219265, year = {2019}, author = {Tytgat, HLP and Nobrega, FL and van der Oost, J and de Vos, WM}, title = {Bowel Biofilms: Tipping Points between a Healthy and Compromised Gut?.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {17-25}, doi = {10.1016/j.tim.2018.08.009}, pmid = {30219265}, issn = {1878-4380}, abstract = {Bacterial communities are known to impact human health and disease. Mixed species biofilms, mostly pathogenic in nature, have been observed in dental and gastric infections as well as in intestinal diseases, chronic gut wounds and colon cancer. Apart from the appendix, the presence of thick polymicrobial biofilms in the healthy gut mucosa is still debated. Polymicrobial biofilms containing potential pathogens appear to be an early-warning signal of developing disease and can be regarded as a tipping point between a healthy and a diseased state of the gut mucosa. Key biofilm-forming pathogens and associated molecules hold promise as biomarkers. Criteria to distinguish microcolonies from biofilms are crucial to provide clarity when reporting biofilm-related phenomena in health and disease in the gut.}, } @article {pmid30219108, year = {2018}, author = {Zarei, O and Shokoohizadeh, L and Hossainpour, H and Alikhani, MY}, title = {Molecular analysis of Pseudomonas aeruginosa isolated from clinical, environmental and cockroach sources by ERIC-PCR.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {668}, pmid = {30219108}, issn = {1756-0500}, mesh = {Animals ; Anti-Bacterial Agents ; Cockroaches/*microbiology ; Cross-Sectional Studies ; Enterobacteriaceae ; Hospitals ; Humans ; Iran ; Microbial Sensitivity Tests ; Polymerase Chain Reaction ; Pseudomonas Infections ; Pseudomonas aeruginosa/*genetics/isolation & purification ; }, abstract = {OBJECTIVE: The objective of this study was to investigate the antibiotic susceptibility, virulence factors and clonal relationship among Pseudomonas aeruginosa isolated from environmental sources, hospitalized patients and the surfaces of cockroaches in the ICUs of four hospitals in Hamadan, west of Iran. A total of 237, 286 and 156 bacterial isolates were collected from clinical, environmental and cockroach sources respectively from May to September, 2017. The antimicrobial susceptibility was determined using disk diffusion method. The virulence factors, exotoxins A, S and U were detected by PCR. The genetic linkage of P. aeruginosa isolates were analyzed by Enterobacterial Repetitive Intergenic Consensus (ERIC)-PCR.

RESULTS: According to our findings, 58 (24.4%), 46 (16%) and 5 (3.25) P. aeruginosa were isolated from clinical, environmental and cockroach samples respectively. The MDR phenotypes were detected in 18 (45%) and 15 (37.5%) of clinical and environmental strains. The environmental isolates harbored more exoA and exoS than did clinical isolates. Genetic diversity was established among P. aeruginosa isolates as 14 different ERIC fingerprints were detected. The clonal relationships was detected among clinical, environmental and cockroach isolates. Our results highlighted the importance of identifying and controlling the potential sources of P. aeruginosa infections in hospitals.}, } @article {pmid30219104, year = {2018}, author = {Nygaard, AB and Charnock, C}, title = {Longitudinal development of the dust microbiome in a newly opened Norwegian kindergarten.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {159}, pmid = {30219104}, issn = {2049-2618}, abstract = {BACKGROUND: In Norway, 91% of children aged 1-5 attend kindergarten where they are exposed to indoor microbiomes which can have relevance for development and health. In order to gain a better understanding of the composition of the indoor microbiome and how it is affected by occupancy over time, floor dust samples from a newly opened kindergarten were investigated. Samples were collected during an 11-month period. Samples were analyzed for bacterial composition using 16S rRNA gene sequencing. Samples were also screened for four clinically relevant antibiotic resistance genes. In addition, Petrifilm analyses were used to evaluate surface hygiene.

RESULTS: Significant changes in the microbial community composition were observed over time (PERMANOVA, P < 0.05). Particularly, changes in the abundance and the proportions of human associated bacteria were found. A decrease in the prevalence of Propionibacterium from over 16% abundance to less than 1% and an increase in Streptococcus from 10 to 16% were the most significant findings. Four classes of clinically relevant antibiotic resistance genes were tested for; three were detected in the dust, indicating the presence of resistant bacteria and a potential for resistance spread. Petrifilm analysis showed that some surfaces in the kindergarten were of consistent poor hygienic quality, and new hygienic routines are required.

CONCLUSIONS: This study, which is the first of its kind performed at a newly opened kindergarten, reveals changes in the microbiome over time as well as the presence of antibiotic resistance genes and hygiene issues which are of relevance for occupant health.}, } @article {pmid30219103, year = {2018}, author = {Uritskiy, GV and DiRuggiero, J and Taylor, J}, title = {MetaWRAP-a flexible pipeline for genome-resolved metagenomic data analysis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {158}, pmid = {30219103}, issn = {2049-2618}, support = {T32 GM007231/GM/NIGMS NIH HHS/United States ; U41 HG006620/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: The study of microbiomes using whole-metagenome shotgun sequencing enables the analysis of uncultivated microbial populations that may have important roles in their environments. Extracting individual draft genomes (bins) facilitates metagenomic analysis at the single genome level. Software and pipelines for such analysis have become diverse and sophisticated, resulting in a significant burden for biologists to access and use them. Furthermore, while bin extraction algorithms are rapidly improving, there is still a lack of tools for their evaluation and visualization.

RESULTS: To address these challenges, we present metaWRAP, a modular pipeline software for shotgun metagenomic data analysis. MetaWRAP deploys state-of-the-art software to handle metagenomic data processing starting from raw sequencing reads and ending in metagenomic bins and their analysis. MetaWRAP is flexible enough to give investigators control over the analysis, while still being easy-to-install and easy-to-use. It includes hybrid algorithms that leverage the strengths of a variety of software to extract and refine high-quality bins from metagenomic data through bin consolidation and reassembly. MetaWRAP's hybrid bin extraction algorithm outperforms individual binning approaches and other bin consolidation programs in both synthetic and real data sets. Finally, metaWRAP comes with numerous modules for the analysis of metagenomic bins, including taxonomy assignment, abundance estimation, functional annotation, and visualization.

CONCLUSIONS: MetaWRAP is an easy-to-use modular pipeline that automates the core tasks in metagenomic analysis, while contributing significant improvements to the extraction and interpretation of high-quality metagenomic bins. The bin refinement and reassembly modules of metaWRAP consistently outperform other binning approaches. Each module of metaWRAP is also a standalone component, making it a flexible and versatile tool for tackling metagenomic shotgun sequencing data. MetaWRAP is open-source software available at https://github.com/bxlab/metaWRAP .}, } @article {pmid30219094, year = {2018}, author = {Bope, A and Weir, MH and Pruden, A and Morowitz, M and Mitchell, J and Dannemiller, KC}, title = {Translating research to policy at the NCSE 2017 symposium "Microbiology of the Built Environment: Implications for Health and Design".}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {160}, pmid = {30219094}, issn = {2049-2618}, abstract = {Here, we summarize a symposium entitled "Microbiology of the Built Environment: Implications for Health and Design" that was presented at the National Council for Science and the Environment (NCSE) 17th National Conference and Global Forum in January 2017. We covered topics including indoor microbial exposures and childhood asthma, the influence of hospital design on neonatal development, the role of the microbiome in our premise (i.e., building) plumbing systems, antibiotic resistance, and quantitative microbial risk assessment. This symposium engaged the broader scientific and policy communities in a discussion to increase awareness of this critical research area and translate findings to practice.}, } @article {pmid30219055, year = {2018}, author = {Han, H and Wang, Q and Wei, L and Liang, Y and Dai, J and Xia, G and Liu, S}, title = {Small RNA and degradome sequencing used to elucidate the basis of tolerance to salinity and alkalinity in wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {195}, pmid = {30219055}, issn = {1471-2229}, support = {31722038//National Natural Science Foundation of China/ ; 31720103910//National Natural Science Foundation of China/ ; 31872864//National Natural Science Foundation of China/ ; 2016WLJH39//Young Scholars Program of Shandong University/ ; 2014JC048//Fundamental Research Funds of Shandong University/ ; }, mesh = {Gene Expression Regulation, Plant ; Gene Silencing ; MicroRNAs/*genetics ; Plants, Genetically Modified ; RNA, Plant/*genetics ; Reproducibility of Results ; Salinity ; Salt Tolerance/*genetics ; Soil/chemistry ; Stress, Physiological/genetics ; Triticum/*genetics/physiology ; }, abstract = {BACKGROUND: Soil salinity and/or alkalinity impose a major constraint over crop yield and quality. An understanding of the molecular basis of the plant response to these stresses could inform the breeding of more tolerant varieties. The bread wheat cultivar SR3 exhibits an enhanced level of salinity tolerance, while SR4 is distinguished by its superior tolerance of alkalinity.

RESULTS: The small RNA and degradome sequencing was used to explore the miRNAs and corresponding targets associated with the superior stress tolerance of the SR lines. An examination of the small RNA content of these two closely related lines revealed the presence of 98 known and 219 novel miRNA sequences. Degradome libraries were constructed in order to identify the targets of the miRNAs, leading to the identification of 58 genes targeted by 26 of the known miRNAs and 549 targeted by 65 of the novel ones. The function of two of the stress-responsive miRNAs was explored using virus-induced gene silencing.

CONCLUSIONS: This analysis indicated that regulation mediated by both auxin and epigenetic modification can be important in determining both salinity and alkalinity tolerance, while jasmonate signaling and carbohydrate metabolism are important for salinity tolerance, as is proton transport for alkalinity tolerance.}, } @article {pmid30219030, year = {2018}, author = {Micheletti, SJ and Hess, JE and Zendt, JS and Narum, SR}, title = {Selection at a genomic region of major effect is responsible for evolution of complex life histories in anadromous steelhead.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {140}, pmid = {30219030}, issn = {1471-2148}, mesh = {Animal Migration/*physiology ; Animals ; *Biological Evolution ; Chromosomes ; Genetic Variation ; Genetics, Population ; *Genome ; Geography ; Haplotypes/genetics ; Likelihood Functions ; Oncorhynchus mykiss/*genetics/*physiology ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; *Selection, Genetic ; }, abstract = {BACKGROUND: Disparity in the timing of biological events occurs across a variety of systems, yet the understanding of genetic basis underlying diverse phenologies remains limited. Variation in maturation timing occurs in steelhead trout, which has been associated with greb1L, an oestrogen target gene. Previous techniques that identified this gene only accounted for about 0.5-2.0% of the genome and solely investigated coastal populations, leaving uncertainty on the genetic basis of this trait and its prevalence across a larger geographic scale.

RESULTS: We used a three-tiered approach to interrogate the genomic basis of complex phenology in anadromous steelhead. First, fine scale mapping with 5.3 million SNPs from resequencing data covering 68% of the genome confirmed a 309-kb region consisting of four genes on chromosome 28, including greb1L, to be the genomic region of major effect for maturation timing. Second, broad-scale characterization of candidate greb1L genotypes across 59 populations revealed unexpected patterns in maturation phenology for inland fish migrating long distances relative to those in coastal streams. Finally, genotypes from 890 PIT-tag tracked steelhead determined associations with early versus late arrival to spawning grounds that were previously unknown.

CONCLUSIONS: This study clarifies the genetic bases for disparity in phenology observed in steelhead, determining an unanticipated trait association with premature versus mature arrival to spawning grounds and identifying multiple candidate genes potentially contributing to this variation from a single genomic region of major effect. This illustrates how dense genome mapping and detailed phenotypic characterization can clarify genotype to phenotype associations across geographic ranges of species.}, } @article {pmid30219026, year = {2018}, author = {Kongari, R and Rajaure, M and Cahill, J and Rasche, E and Mijalis, E and Berry, J and Young, R}, title = {Phage spanins: diversity, topological dynamics and gene convergence.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {326}, pmid = {30219026}, issn = {1471-2105}, support = {R01 GM027099/GM/NIGMS NIH HHS/United States ; R37 GM027099/GM/NIGMS NIH HHS/United States ; GM27099//U.S. Public Health Service/ ; }, mesh = {Amino Acid Sequence ; Bacteriophage lambda/genetics/*metabolism ; Protein Conformation ; Protein Domains ; Sequence Homology ; Viral Proteins/chemistry/*genetics/*metabolism ; }, abstract = {BACKGROUND: Spanins are phage lysis proteins required to disrupt the outer membrane. Phages employ either two-component spanins or unimolecular spanins in this final step of Gram-negative host lysis. Two-component spanins like Rz-Rz1 from phage lambda consist of an integral inner membrane protein: i-spanin, and an outer membrane lipoprotein: o-spanin, that form a complex spanning the periplasm. Two-component spanins exist in three different genetic architectures; embedded, overlapped and separated. In contrast, the unimolecular spanins, like gp11 from phage T1, have an N-terminal lipoylation signal sequence and a C-terminal transmembrane domain to account for the topology requirements. Our proposed model for spanin function, for both spanin types, follows a common theme of the outer membrane getting fused with the inner membrane, effecting the release of progeny virions.

RESULTS: Here we present a SpaninDataBase which consists of 528 two-component spanins and 58 unimolecular spanins identified in this analysis. Primary analysis revealed significant differences in the secondary structure predictions for the periplasmic domains of the two-component and unimolecular spanin types, as well as within the three different genetic architectures of the two-component spanins. Using a threshold of 40% sequence identity over 40% sequence length, we were able to group the spanins into 143 i-spanin, 125 o-spanin and 13 u-spanin families. More than 40% of these families from each type were singletons, underlining the extreme diversity of this class of lysis proteins. Multiple sequence alignments of periplasmic domains demonstrated conserved secondary structure patterns and domain organization within family members. Furthermore, analysis of families with members from different architecture allowed us to interpret the evolutionary dynamics of spanin gene arrangement. Also, the potential universal role of intermolecular disulfide bonds in two-component spanin function was substantiated through bioinformatic and genetic approaches. Additionally, a novel lipobox motif, AWAC, was identified and experimentally verified.

CONCLUSIONS: The findings from this bioinformatic approach gave us instructive insights into spanin function, evolution, domain organization and provide a platform for future spanin annotation, as well as biochemical and genetic experiments. They also establish that spanins, like viral membrane fusion proteins, adopt different strategies to achieve fusion of the inner and outer membranes.}, } @article {pmid30218951, year = {2018}, author = {Salam, AM and Quave, CL}, title = {Opportunities for plant natural products in infection control.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {189-194}, doi = {10.1016/j.mib.2018.08.004}, pmid = {30218951}, issn = {1879-0364}, support = {R21 AI136563/AI/NIAID NIH HHS/United States ; }, abstract = {The continued spread of antimicrobial resistance represents one of the most serious infectious disease threats to global health. There is consensus that a key component of addressing this threat is to replenish the waning pipeline of antimicrobials, with attention being paid to novel mechanisms of action. This includes the development of new classes of classic bacteriostatic and bactericidal antibiotics as well as antivirulence drugs, and it is especially in these areas where plant natural products demonstrate great potential. To this end, we discuss the unique characteristics of plant natural products, the advantages of plants as a resource for anti-infective drug discovery, and recent technologies that have further enabled this path of inquiry. As a result of emerging realization of their advantages, plant natural products have recently enjoyed increased scrutiny in antimicrobial lead discovery, and they will continue to serve as a source of leads. We conclude that plant natural products represent a promising and largely untapped source of new chemical entities from which novel anti-infectives can be discovered.}, } @article {pmid30218775, year = {2018}, author = {Antoniou, A and Frantzis, A and Alexiadou, P and Paschou, N and Poulakakis, N}, title = {Evidence of introgressive hybridization between Stenella coeruleoalba and Delphinus delphis in the Greek Seas.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {325-337}, doi = {10.1016/j.ympev.2018.09.007}, pmid = {30218775}, issn = {1095-9513}, abstract = {Natural interspecific hybridization might be more important for the evolutionary history and speciation of animals than previously thought, considering several demographic and life history traits as well as habitat disturbance as factors that promote it. In this aspect, cetaceans comprise an interesting case in which the occurrence of sympatric species in mixed associations provides excellent opportunities for interspecific sexual interaction and the potential for hybridization. Here, we present evidence of natural hybridization for two cetacean species commonly occurring in the Greek Seas (Stenella coeruleoalba and Delphinus delphis), which naturally overlap in the Gulf of Corinth by analyzing highly resolving microsatellite DNA markers and mitochondrial DNA sequences in skin samples from 45 individuals of S. coeruleoalba, 12 D. delphis and three intermediate morphs. Employing several phylogenetic and population genetic approaches, we found 15 individuals that are potential hybrids including the three intermediate morphs, verifying the occurrence of natural hybridization between species of different genera. Their hybrids are fertile and able to reproduce not only with the other hybrids but also with each of the two-parental species. However, current evidence does not allow firm conclusions whether hybridization might constitute a step towards the generation of a new species and/or the swan song of an already existing species (i.e., D. delphis). Given that the focal species form mixed pods in several areas of Mediterranean, this study is an excellent opportunity to understand the mechanisms leading to hybridization in the context of gene flow and urges for the evaluation of the genetic status of common dolphins in the Mediterranean.}, } @article {pmid30218774, year = {2018}, author = {Wang, P and Yao, H and Gilbert, KJ and Lu, Q and Hao, Y and Zhang, Z and Wang, N}, title = {Glaciation-based isolation contributed to speciation in a Palearctic alpine biodiversity hotspot: Evidence from endemic species.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {315-324}, doi = {10.1016/j.ympev.2018.09.006}, pmid = {30218774}, issn = {1095-9513}, abstract = {Organisms are unevenly distributed on earth and the evolutionary drivers of that have puzzled ecologists and evolutionary biologists for over a century. Even though many studies have focused on the mechanisms of unevenly distributed fauna and flora, there remains much to learn about the evolutionary drivers behind biodiversity hotspots. In the Tibetan Plateau and Hengduan Mountains, a biodiversity hotspot in the Palearctic realm, alpine uplift cannot be the driver for recent speciation (
RESULTS: A total of 12 cases of suspected Basidiobolomycosis have been identified. The sex ratio (M/F) was 2. The average age of the patients was 24.8 ± 1.6 years. Six patients (6/12) had a pathological history: HIV infection (n = 4 cases) and tuberculosis (n = 2 cases). The clinical manifestations were localized to pure skin (n = 9 cases), skin and mucous digestive (n = 2 cases) and disseminated (n = 1 cases). Direct mycological examination and culture in 4 patients was positive in 3 patients. The samples examined consisted of 11 cutaneous biopsies measuring 1-3 cm and a biopsy of the intestinal mucosa. Histology showed granulomatous inflammation of the dermohypodermal site with numerous giant cells associated with eosinophilic polynuclear cells, in which there are 5-7 mm non-septate, irregular mycelial filaments. Patients were treated with ketoconazole at a dose of 10 mg/kg daily. The progression of the patients' condition was favorable after 4 weeks of treatment with a regression of the closets size. Patients were completely healed after 8 weeks of treatment, without recurrence after 6 months. No deaths have been recorded.}, } @article {pmid30217178, year = {2018}, author = {Chen, H and Zhang, Q and He, M and Wang, S and Shi, L and Xu, F}, title = {Molecular characterization of the genome-wide BOR transporter gene family and genetic analysis of BnaC04.BOR1;1c in Brassica napus.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {193}, pmid = {30217178}, issn = {1471-2229}, support = {2016YFD0100700//National Key Research and Development Program of China/ ; }, mesh = {Boron/metabolism ; Brassica napus/*genetics/metabolism ; Carrier Proteins/metabolism ; Chromosomes, Plant ; *Gene Expression Regulation, Plant ; Genome, Plant ; Multigene Family ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Plant Shoots/genetics ; Plants, Genetically Modified ; Promoter Regions, Genetic ; }, abstract = {BACKGROUND: Boron (B) deficiency is an agricultural problem that causes significant losses of crop yield in many areas of the world. However, systematic analysis of BOR family genes for B transport in rapeseed is still lacking. We aimed to identify and characterize BOR transporters in Brassica napus and the potential role of these transporters in B homeostasis in response to B deficiency.

RESULTS: Here, we identified 20 BOR transporters from the Brassica napus genome, which were classified into six distinct groups that represent clear orthologous relationships to their family members in Arabidopsis. qRT-PCR revealed distinct expression profiles for BnBORs in different tissues and in response to external B levels. The B-efficient cultivar QY10 accumulated more B in shoots than the B-inefficient cultivar W10, and overexpression of BnaBOR1;1c could alleviate shoot B-deficiency symptoms in W10 by distributing more B from roots to shoots. Additionally, BnBOR1;1c expression was up-regulated by B deficiency, and the induction of BnBOR1;1c was more intense in QY10. Moreover, two conserved InDels were found in the promoter regions of BnBOR1;1c within different B-efficient genotypes.

CONCLUSIONS: Overall, the molecular characterization of the BnBOR genes of two B-efficient cultivars and their responses to B deficiency highlights the diversity of the family members in B. napus, and BnaC4.BOR1;1c has potential as a candidate gene for improving B nutrition.}, } @article {pmid30217175, year = {2018}, author = {Wu, W and Ng, WL and Yang, JX and Li, WM and Ge, XJ}, title = {High cryptic species diversity is revealed by genome-wide polymorphisms in a wild relative of banana, Musa itinerans, and implications for its conservation in subtropical China.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {194}, pmid = {30217175}, issn = {1471-2229}, support = {31261140366//National Natural Science Foundation of China/ ; }, mesh = {Bayes Theorem ; China ; Genetic Variation ; Genome, Plant ; Musa/classification/*genetics ; Phylogeography ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Species delimitation is a challenging but essential task in conservation biology. Morphologically similar species are sometimes difficult to recognize even after examination by experienced taxonomists. With the advent of molecular approaches in species delimitation, this hidden diversity has received much recent attention. In addition to DNA barcoding approaches, analytical tools based on the multi-species coalescence model (MSC) have been developed for species delimitation. Musa itinerans is widely distributed in subtropical Asia, and at least six varieties have been documented. However, the number of evolutionarily distinct lineages remains unknown.

RESULTS: Using genome resequencing data of five populations (making up four varieties), we examined genome-wide variation and found four varieties that were evolutionary significant units. A Bayesian Phylogenetics and Phylogeography (BP&P) analysis using 123 single copy nuclear genes support three speciation events of M. itinerans varieties with robust posterior speciation probabilities; However, a Bayes factor delimitation of species with genomic data (BFD*) analysis using 1201 unlinked single nucleotide polymorphisms gave decisive support for a five-lineage model. When reconciling divergence time estimates with a speciation time scale, a modified three-lineage model was consistent with that of BP&P, in which the speciation time of two varieties (M. itinerans var. itinerans and M. itinerans var. lechangensis) were dated to 26.2 kya and 10.7 kya, respectively. In contrast, other two varieties (M. itinerans var. chinensis and M. itinerans var. guangdongensis) diverged only 3.8 kya in the Anthropocene; this may be a consequence of genetic drift rather than a speciation event.

CONCLUSION: Our results showed that the M. itinerans species complex harbours high cryptic species diversity. We recommend that M. itinerans var. itinerans and M. itinerans var. lechangensis be elevated to subspecies status, and the extremely rare latter subspecies be given priority for conservation. We also recommend that the very recently diverged M. itinerans var. chinensis and M. itinerans var. guangdongensis should be merged under the subspecies M. itinerans var. chinensis. Finally, we speculate that species delimitation of recently diverged lineages may be more effective using genome-wide bi-allelic SNP markers with BFD* than by using unlinked loci and BP&P.}, } @article {pmid30217158, year = {2018}, author = {Brannelly, LA and Chatfield, MWH and Sonn, J and Robak, M and Richards-Zawacki, CL}, title = {Fungal infection has sublethal effects in a lowland subtropical amphibian population.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {34}, pmid = {30217158}, issn = {1472-6785}, support = {LEQSF (2011-14)-RD-A-26//Louisiana Board of Regents/International ; }, abstract = {BACKGROUND: The amphibian chytrid fungus, Batrachochytrium dendrobatidis (Bd), has been implicated as a primary cause of decline in many species around the globe. However, there are some species and populations that are known to become infected in the wild, yet declines have not been observed. Here we conducted a yearlong capture-mark-recapture study and a 2-year long disease monitoring study of northern cricket frogs, Acris crepitans, in the lowland subtropical forests of Louisiana.

RESULTS: We found little evidence for an impact of Bd infection on survival; however, Bd infection did appear to cause sublethal effects, including increased capture probability in the field.

CONCLUSIONS: Our study suggests that even in apparently stable populations, where Bd does not appear to cause mortality, there may be sublethal effects of infection that can impact a host population's dynamics and structure. Understanding and documenting such sublethal effects of infection on wild, seemingly stable populations is important, particularly for predicting future population declines.}, } @article {pmid30217149, year = {2018}, author = {Baker, LY and Hobby, CR and Siv, AW and Bible, WC and Glennon, MS and Anderson, DM and Symes, SJ and Giles, DK}, title = {Pseudomonas aeruginosa responds to exogenous polyunsaturated fatty acids (PUFAs) by modifying phospholipid composition, membrane permeability, and phenotypes associated with virulence.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {117}, pmid = {30217149}, issn = {1471-2180}, abstract = {BACKGROUND: Pseudomonas aeruginosa, a common opportunistic pathogen, is known to cause infections in a variety of compromised human tissues. An emerging mechanism for microbial survival is the incorporation of exogenous fatty acids to alter the cell's membrane phospholipid profile. With these findings, we show that exogenous fatty acid exposure leads to changes in bacterial membrane phospholipid structure, membrane permeability, virulence phenotypes and consequent stress responses that may influence survival and persistence of Pseudomonas aeruginosa.

RESULTS: Thin-layer chromatography and ultra performance liquid chromatography / ESI-mass spectrometry indicated alteration of bacterial phospholipid profiles following growth in the presence of polyunsaturated fatty acids (PUFAs) (ranging in carbon length and unsaturation). The exogenously supplied fatty acids were incorporated into the major bacterial phospholipids phosphatidylethanolamine and phosphatidylglycerol. The incorporation of fatty acids increased membrane permeability as judged by both accumulation and exclusion of ethidium bromide. Individual fatty acids were identified as modifying resistance to the cyclic peptide antibiotics polymyxin B and colistin, but not the beta-lactam imipenem. Biofilm formation was increased by several PUFAs and significant fluctuations in swimming motility were observed.

CONCLUSIONS: Our results emphasize the relevance and complexity of exogenous fatty acids in the membrane physiology and pathobiology of a medically important pathogen. P. aeruginosa exhibits versatility with regard to utilization of and response to exogenous fatty acids, perhaps revealing potential strategies for prevention and control of infection.}, } @article {pmid30217148, year = {2018}, author = {Parks, MM and Raphael, BJ and Lawrence, CE}, title = {Using controls to limit false discovery in the era of big data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {323}, pmid = {30217148}, issn = {1471-2105}, support = {R01 HG005690/HG/NHGRI NIH HHS/United States ; R01HG5690//National Human Genome Research Institute/ ; CCF-1053753//Directorate for Mathematical and Physical Sciences/ ; }, mesh = {Bayes Theorem ; DNA Repair ; Databases, Factual ; Genome, Human ; Humans ; *Models, Statistical ; }, abstract = {BACKGROUND: Procedures for controlling the false discovery rate (FDR) are widely applied as a solution to the multiple comparisons problem of high-dimensional statistics. Current FDR-controlling procedures require accurately calculated p-values and rely on extrapolation into the unknown and unobserved tails of the null distribution. Both of these intermediate steps are challenging and can compromise the reliability of the results.

RESULTS: We present a general method for controlling the FDR that capitalizes on the large amount of control data often found in big data studies to avoid these frequently problematic intermediate steps. The method utilizes control data to empirically construct the distribution of the test statistic under the null hypothesis and directly compares this distribution to the empirical distribution of the test data. By not relying on p-values, our control data-based empirical FDR procedure more closely follows the foundational principles of the scientific method: that inference is drawn by comparing test data to control data. The method is demonstrated through application to a problem in structural genomics.

CONCLUSIONS: The method described here provides a general statistical framework for controlling the FDR that is specifically tailored for the big data setting. By relying on empirically constructed distributions and control data, it forgoes potentially problematic modeling steps and extrapolation into the unknown tails of the null distribution. This procedure is broadly applicable insofar as controlled experiments or internal negative controls are available, as is increasingly common in the big data setting.}, } @article {pmid30217147, year = {2018}, author = {Noble, PA and Pozhitkov, AE}, title = {Cryptic sequence features in the active postmortem transcriptome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {675}, pmid = {30217147}, issn = {1471-2164}, mesh = {3' Untranslated Regions ; 5' Untranslated Regions ; Animals ; Base Sequence ; Binding Sites/genetics ; Databases, Genetic ; Mice ; MicroRNAs/genetics ; Open Reading Frames ; *Postmortem Changes ; *RNA Processing, Post-Transcriptional ; RNA, Messenger/genetics ; RNA-Binding Proteins/genetics ; Stress, Physiological/genetics ; *Transcriptome ; Zebrafish/*genetics ; }, abstract = {BACKGROUND: Our previous study found that more than 500 transcripts significantly increased in abundance in the zebrafish and mouse several hours to days postmortem relative to live controls. The current literature suggests that most mRNAs are post-transcriptionally regulated in stressful conditions. We rationalized that the postmortem transcripts must contain sequence features (3- to 9- mers) that are unique from those in the rest of the transcriptome and that these features putatively serve as binding sites for proteins and/or non-coding RNAs involved in post-transcriptional regulation.

RESULTS: We identified 5117 and 2245 over-represented sequence features in the mouse and zebrafish, respectively, which represents less than 1.5% of all possible features. Some of these features were disproportionately distributed along the transcripts with high densities in the 3' untranslated regions of the zebrafish (0.3 mers/nt) and the open reading frames of the mouse (0.6 mers/nt). Yet, the highest density (2.3 mers/nt) occurred in the open reading frames of 11 mouse transcripts that lacked 3' or 5' untranslated regions. These results suggest the transcripts with high density of features might serve as 'molecular sponges' that sequester RNA binding proteins and/or microRNAs, and thus indirectly increase the stability and gene expression of other transcripts. In addition, some of the features were identified as binding sites for Rbfox and Hud proteins that are also involved in increasing transcript stability and gene expression.

CONCLUSIONS: Our results are consistent with the hypothesis that transcripts involved in responding to extreme stress, such as organismal death, have sequence features that make them different from the rest of the transcriptome. Some of these features serve as putative binding sites for proteins and non-coding RNAs that determine transcript stability and fate. A small number of the transcripts have high density sequence features, which are presumably involved in sequestering RNA binding proteins and microRNAs and thus preventing regulatory interactions among other transcripts. Our results provide baseline data on post-transcriptional regulation in stressful conditions that has implications for regulation in disease, starvation, and cancer.}, } @article {pmid30217145, year = {2018}, author = {Wei, W and Chen, K and Miao, W and Yang, W and Xiong, J}, title = {Pseudocohnilembus persalinus genome database - the first genome database of facultative scuticociliatosis pathogens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {676}, pmid = {30217145}, issn = {1471-2164}, support = {31525021//National Natural Science Foundation of China/ ; 31672281//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Base Sequence ; Ciliophora/genetics ; Databases, Genetic ; *Genome, Protozoan ; Genomics ; Molecular Sequence Annotation ; Oligohymenophorea/*genetics ; Transcriptome ; }, abstract = {BACKGROUND: Pseudocohnilembus persalinus, a unicellular ciliated protozoan, is one of commonest facultative pathogens. We sequenced the macronuclear genome of P. persalinus in 2015, which provided new insights into its pathogenicity.

RESULTS: Here, we present the P. persalinus genome database (PPGD) (http://ciliates.ihb.ac.cn/database/home/#pp), the first genome database for the scuticociliatosis pathogens. PPGD integrates P. persalinus macronuclear genomic and transcriptomic data, including genome sequence, transcript, gene expression data, and gene annotation, as well as relevant information on its biology, morphology and taxonomy. The database also provides functions for visualizing, analyzing, and downloading the data.

CONCLUSION: PPGD is a useful resource for studying scuticociliates or scuticociliatosis. We will continue to update the PPGD by integrating more data and aim to integrate the PPGD with other ciliate databases to build a comprehensive ciliate genome database.}, } @article {pmid30217144, year = {2018}, author = {Tamura, T}, title = {Grid-based computational methods for the design of constraint-based parsimonious chemical reaction networks to simulate metabolite production: GridProd.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {325}, pmid = {30217144}, issn = {1471-2105}, support = {16K00391//Japan Society for the Promotion of Science/ ; 16H02485//Japan Society for the Promotion of Science/ ; }, mesh = {*Algorithms ; Carbon/metabolism ; Computational Biology/*methods ; Escherichia coli/genetics/metabolism ; Genome, Bacterial ; Metabolic Flux Analysis ; Metabolic Networks and Pathways ; }, abstract = {BACKGROUND: Constraint-based metabolic flux analysis of knockout strategies is an efficient method to simulate the production of useful metabolites in microbes. Owing to the recent development of technologies for artificial DNA synthesis, it may become important in the near future to mathematically design minimum metabolic networks to simulate metabolite production.

RESULTS: We have developed a computational method where parsimonious metabolic flux distribution is computed for designated constraints on growth and production rates which are represented by grids. When the growth rate of this obtained parsimonious metabolic network is maximized, higher production rates compared to those noted using existing methods are observed for many target metabolites. The set of reactions used in this parsimonious flux distribution consists of reactions included in the original genome scale model iAF1260. The computational experiments show that the grid size affects the obtained production rates. Under the conditions that the growth rate is maximized and the minimum cases of flux variability analysis are considered, the developed method produced more than 90% of metabolites, while the existing methods produced less than 50%. Mathematical explanations using examples are provided to demonstrate potential reasons for the ability of the proposed algorithm to identify design strategies that the existing methods could not identify.

CONCLUSION: We developed an efficient method for computing the design of minimum metabolic networks by using constraint-based flux balance analysis to simulate the production of useful metabolites. The source code is freely available, and is implemented in MATLAB and COBRA toolbox.}, } @article {pmid30217143, year = {2018}, author = {Su, HA and Bai, X and Zeng, T and Lu, YY and Qi, YX}, title = {Identification, characterization and expression analysis of transient receptor potential channel genes in the oriental fruit fly, Bactrocera dorsalis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {674}, pmid = {30217143}, issn = {1471-2164}, support = {2016YFC1201200//National key research and development project/ ; 2018A030310204//Natural Science Foundation of Guangdong Province (CN)/ ; }, mesh = {Amino Acid Sequence ; Animals ; Databases, Genetic ; Female ; Gene Expression Regulation, Developmental ; Genes, Insect/*genetics ; Genome, Insect ; Insecta/genetics ; Male ; Phylogeny ; Protein Isoforms ; Species Specificity ; TRPP Cation Channels/genetics ; Tephritidae/*genetics/growth & development ; Tissue Distribution ; Transcriptome ; Transient Receptor Potential Channels/*genetics/physiology ; }, abstract = {BACKGROUND: Members of the transient receptor potential (TRP) superfamily are proteins that are critical for insects to detect changes in environmental stimuli and also play key roles in their sensory physiology. Moreover, this family provides potential targets for the design of insecticides. In contrast to a large number of studies conducted on Drosophila melanogaster, molecular studies to characterize TRP channels in agricultural pests are lacking.

RESULTS: In this study, we identified 15 TRP channel genes in the genome of a notorious agricultural pest, the oriental fruit fly (Bactrocera dorsalis). Comparative analysis of the TRP channels (TRPs) in B. dorsalis with those in D. melanogaster, Glossina morsitans, Musca domestica and the closely related Ceratitis capitata, and TRPs from mosquitoes, Hymenoptera, Lepidoptera, Coleoptera and Hemiptera reveals that members of TRPA and TRPP subfamily are most diverse among insects. The results also suggest that Tephritidae family have two TRP-Polycystin 2 members even though most insects either possess just one or none. The highest expression levels of these two genes are in the testes of B. dorsalis, implying a role in regulating sperm function. We analyzed the expression profiles of the TRP channels identified in this study at different life stages using quantitative real time PCR. The results of this study demonstrate that all TRP channels are mainly expressed in adults, especially at mature stages. The one exception to this trend is BdTRPM, which is more highly expressed in the eggs of B. dorsalis, implying an important role in early development. We also detected the spatial expression of TRP channels in mature adult fruit flies by investigating expression levels within various tissues including those involved in sensory function, such as antennae, compound eyes, mouthparts, legs, and wings, as well as tissues critical for homeostasis and physiology (i.e., Malpighian tubules, the brain and gut as well as fat bodies, ovaries, and testes).

CONCLUSION: The results of this study establish a solid foundation for future functional characterization of B. dorsalis TRP channels as well as those of other insects and will help future insecticide design targeting these channels.}, } @article {pmid30217140, year = {2018}, author = {Baygents, G and Bani-Yaghoub, M}, title = {Cluster analysis of hemorrhagic disease in Missouri's white-tailed deer population: 1980-2013.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {35}, pmid = {30217140}, issn = {1472-6785}, support = {KCS21//University of Missouri-Kansas City/International ; }, abstract = {BACKGROUND: Outbreaks of deer hemorrhagic disease (HD) have been documented in the USA for many decades. In the year 2012, there was a severe HD outbreak in Missouri with mortalities reaching approximately 6.9 per thousand. Moreover, Missouri accounted for more than 43% of all reported epizootic HD cases in captive white-tailed deer. Using the data of suspected HD occurrence in Missouri, the primary goal of this paper was to determine if HD in Missouri's white-tailed deer occurs in spatial clusters.

RESULTS: The main results of the cluster analysis are as follows. First, the spatial clusters of years 1980, 1988, 2005-2007, 2010, 2012, and 2013 suggest patterns of outbreaks every 6-8 years, with a potential outbreak in years 2018-2020. Secondly, these spatial clusters were more frequent in the central and southern counties.

CONCLUSIONS: The clustering analyses employed in this study have potential applications for improving surveillance programs and designing early warning systems for effective deer population management and potentially reducing the number of HD cases.}, } @article {pmid30217139, year = {2018}, author = {Villandré, L and Labbe, A and Brenner, B and Roger, M and Stephens, DA}, title = {DM-PhyClus: a Bayesian phylogenetic algorithm for infectious disease transmission cluster inference.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {324}, pmid = {30217139}, issn = {1471-2105}, support = {(CIHR HHP-126781//Canadian Institutes of Health Research/Canada ; }, mesh = {*Algorithms ; Bayes Theorem ; Cluster Analysis ; HIV Infections/pathology/*transmission/virology ; HIV-1/classification/genetics/isolation & purification ; Homosexuality, Male ; Humans ; Male ; Phylogeny ; Software ; }, abstract = {BACKGROUND: Conventional phylogenetic clustering approaches rely on arbitrary cutpoints applied a posteriori to phylogenetic estimates. Although in practice, Bayesian and bootstrap-based clustering tend to lead to similar estimates, they often produce conflicting measures of confidence in clusters. The current study proposes a new Bayesian phylogenetic clustering algorithm, which we refer to as DM-PhyClus (Dirichlet-Multinomial Phylogenetic Clustering), that identifies sets of sequences resulting from quick transmission chains, thus yielding easily-interpretable clusters, without using any ad hoc distance or confidence requirement.

RESULTS: Simulations reveal that DM-PhyClus can outperform conventional clustering methods, as well as the Gap procedure, a pure distance-based algorithm, in terms of mean cluster recovery. We apply DM-PhyClus to a sample of real HIV-1 sequences, producing a set of clusters whose inference is in line with the conclusions of a previous thorough analysis.

CONCLUSIONS: DM-PhyClus, by eliminating the need for cutpoints and producing sensible inference for cluster configurations, can facilitate transmission cluster detection. Future efforts to reduce incidence of infectious diseases, like HIV-1, will need reliable estimates of transmission clusters. It follows that algorithms like DM-PhyClus could serve to better inform public health strategies.}, } @article {pmid30216739, year = {2019}, author = {Maksym, T}, title = {Arctic and Antarctic Sea Ice Change: Contrasts, Commonalities, and Causes.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {187-213}, doi = {10.1146/annurev-marine-010816-060610}, pmid = {30216739}, issn = {1941-0611}, abstract = {Arctic sea ice has declined precipitously in both extent and thickness over the past four decades; by contrast, Antarctic sea ice has shown little overall change, but this masks large regional variability. Climate models have not captured these changes. But these differences do not represent a paradox. The processes governing, and impacts of, natural variability and human-induced changes differ markedly at the poles largely because of the ways in which differences in geography control the properties of and interactions among the atmosphere, ice, and ocean. The impact of natural variability on the ice cover is large at both poles, so modeled ice trends are not entirely inconsistent with contributions from both natural variability and anthropogenic forcing. Despite this concurrence, the coupling of natural climate variability, climate feedbacks, and sea ice is not well understood, and significant biases remain in model representations of the ice cover and the processes that drive it.}, } @article {pmid30216738, year = {2019}, author = {Calosi, P and Putnam, HM and Twitchett, RJ and Vermandele, F}, title = {Marine Metazoan Modern Mass Extinction: Improving Predictions by Integrating Fossil, Modern, and Physiological Data.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {369-390}, doi = {10.1146/annurev-marine-010318-095106}, pmid = {30216738}, issn = {1941-0611}, abstract = {Evolution, extinction, and dispersion are fundamental processes affecting marine biodiversity. Until recently, studies of extant marine systems focused mainly on evolution and dispersion, with extinction receiving less attention. Past extinction events have, however, helped shape the evolutionary history of marine ecosystems, with ecological and evolutionary legacies still evident in modern seas. Current anthropogenic global changes increase extinction risk and pose a significant threat to marine ecosystems, which are critical for human use and sustenance. The evaluation of these threats and the likely responses of marine ecosystems requires a better understanding of evolutionary processes that affect marine ecosystems under global change. Here, we discuss how knowledge of (a) changes in biodiversity of ancient marine ecosystems to past extinctions events, (b) the patterns of sensitivity and biodiversity loss in modern marine taxa, and (c) the physiological mechanisms underpinning species' sensitivity to global change can be exploited and integrated to advance our critical thinking in this area.}, } @article {pmid30216737, year = {2019}, author = {Hamme, RC and Nicholson, DP and Jenkins, WJ and Emerson, SR}, title = {Using Noble Gases to Assess the Ocean's Carbon Pumps.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {75-103}, doi = {10.1146/annurev-marine-121916-063604}, pmid = {30216737}, issn = {1941-0611}, abstract = {Natural mechanisms in the ocean, both physical and biological, concentrate carbon in the deep ocean, resulting in lower atmospheric carbon dioxide. The signals of these carbon pumps overlap to create the observed carbon distribution in the ocean, making the individual impact of each pump difficult to disentangle. Noble gases have the potential to directly quantify the physical carbon solubility pump and to indirectly improve estimates of the biological organic carbon pump. Noble gases are biologically inert, can be precisely measured, and span a range of physical properties. We present dissolved neon, argon, and krypton data spanning the Atlantic, Southern, Pacific, and Arctic Oceans. Comparisons between deep-ocean observations and models of varying complexity enable the rates of processes that control the carbon solubility pump to be quantified and thus provide an important metric for ocean model skill. Noble gases also provide a powerful means of assessing air-sea gas exchange parameterizations.}, } @article {pmid30216586, year = {2018}, author = {Bichet, C and Lepetit, D and Cohas, A}, title = {Extrinsic and intrinsic constraints interact to drive extra-pair paternities in the Alpine marmot.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1794-1802}, doi = {10.1111/jeb.13374}, pmid = {30216586}, issn = {1420-9101}, support = {ANR-13-JSV7-0005//Centre National de la Recherche Scientifique/ ; }, abstract = {To reproduce, animals have to form pairs and large variations in the degree of mate switching are observed. Extrinsic and intrinsic factors can constrain individual's mate switching. Among intrinsic factors, genes involved in pair-bonding, such as Avpr-1a, receive increasing attention. The length of microsatellites present in the regulatory region of Avpr-1a determines the neural densities and distributions of the vasopressin receptors known to impact pair-bonding behaviours. For the first time, we investigated whether and how the genetic makeup at Avpr-1a, an intrinsic factor, and the social context, an extrinsic factor, experienced by wild Alpine marmot (Marmota marmota) females affect the proportion of extra-pair young. This proportion was positively correlated with the length of their Avpr-1a regulatory region but only when the social constraints were relaxed, that is when mature male subordinates were present. When ignoring the interactive effect between the length of their Avpr-1a regulatory region and the social constraints, the genetic makeup at Avpr-1a was not associated with the proportion of extra-pair young. Under natural conditions, the genetic regulation of pair-bonding could be hidden by extrinsic factors constraining mate choice.}, } @article {pmid30215800, year = {2018}, author = {Glander, S and He, F and Schmitz, G and Witten, A and Telschow, A and de Meaux, J}, title = {Assortment of Flowering Time and Immunity Alleles in Natural Arabidopsis thaliana Populations Suggests Immunity and Vegetative Lifespan Strategies Coevolve.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2278-2291}, pmid = {30215800}, issn = {1759-6653}, abstract = {The selective impact of pathogen epidemics on host defenses can be strong but remains transient. By contrast, life-history shifts can durably and continuously modify the balance between costs and benefits of immunity, which arbitrates the evolution of host defenses. Their impact on the evolutionary dynamics of host immunity, however, has seldom been documented. Optimal investment into immunity is expected to decrease with shortening lifespan, because a shorter life decreases the probability to encounter pathogens or enemies. Here, we document that in natural populations of Arabidopsis thaliana, the expression levels of immunity genes correlate positively with flowering time, which in annual species is a proxy for lifespan. Using a novel genetic strategy based on bulk-segregants, we partitioned flowering time-dependent from -independent immunity genes and could demonstrate that this positive covariation can be genetically separated. It is therefore not explained by the pleiotropic action of some major regulatory genes controlling both immunity and lifespan. Moreover, we find that immunity genes containing variants reported to impact fitness in natural field conditions are among the genes whose expression covaries most strongly with flowering time. Taken together, these analyses reveal that natural selection has likely assorted alleles promoting lower expression of immunity genes with alleles that decrease the duration of vegetative lifespan in A. thaliana and vice versa. This is the first study documenting a pattern of variation consistent with the impact that selection on flowering time is predicted to have on diversity in host immunity.}, } @article {pmid30215746, year = {2018}, author = {}, title = {Undersampling Genomes has Biased Time and Rate Estimates Throughout the Tree of Life.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2595}, doi = {10.1093/molbev/msy151}, pmid = {30215746}, issn = {1537-1719}, } @article {pmid30215710, year = {2018}, author = {Brown, AP and Arias-Rodriguez, L and Yee, MC and Tobler, M and Kelley, JL}, title = {Concordant Changes in Gene Expression and Nucleotides Underlie Independent Adaptation to Hydrogen-Sulfide-Rich Environments.}, journal = {Genome biology and evolution}, volume = {10}, number = {11}, pages = {2867-2881}, pmid = {30215710}, issn = {1759-6653}, abstract = {The colonization of novel environments often involves changes in gene expression, protein coding sequence, or both. Studies of how populations adapt to novel conditions, however, often focus on only one of these two processes, potentially missing out on the relative importance of different parts of the evolutionary process. In this study, our objectives were 1) to better understand the qualitative concordance between conclusions drawn from analyses of differential expression and changes in genic sequence and 2) to quantitatively test whether differentially expressed genes were enriched for sites putatively under positive selection within gene regions. To achieve this, we compared populations of fish (Poecilia mexicana) that have independently adapted to hydrogen-sulfide-rich environments in southern Mexico to adjacent populations residing in nonsulfidic waters. Specifically, we used RNA-sequencing data to compare both gene expression and DNA sequence differences between populations. Analyzing these two different data types led to similar conclusions about which biochemical pathways (sulfide detoxification and cellular respiration) were involved in adaptation to sulfidic environments. Additionally, we found a greater overlap between genes putatively under selection and differentially expressed genes than expected by chance. We conclude that considering both differential expression and changes in DNA sequence led to a more comprehensive understanding of how these populations adapted to extreme environmental conditions. Our results imply that changes in both gene expression and DNA sequence-sometimes at the same loci-may be involved in adaptation.}, } @article {pmid30215596, year = {2018}, author = {Lee, DW and Lee, H and Kwon, BO and Khim, JS and Yim, UH and Kim, BS and Kim, JJ}, title = {Blastococcus litoris sp. nov., isolated from sea-tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3435-3440}, doi = {10.1099/ijsem.0.003004}, pmid = {30215596}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-strain-positive, non-spore-forming bacterial strain, designated GP-S2-8T, was isolated from a sea-tidal flat sediment sample from Gopado, Republic of Korea. Cells were aerobic, catalase-negative, oxidase-positive, non-motile and cocci, occurring singly, in pairs or in tetrads, and often tending to form aggregates. The strain grew at 4-45 °C (optimum, 28-37 °C), at pH 4.0-11.0 (pH 7.0-9.0) and in the presence of 0-11 % (w/v) NaCl (0-3 %). Phylogenetic analyses based on 16S rRNA gene sequences represented that the isolate belongs to the genus Blastococcus. The diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. Whole-cell sugar analysis of strain GP-S2-8T revealed rhamnose, glucose and mannose as characteristic sugars. The predominant respiratory quinone was MK-9(H4) and the major fatty acids were iso-C16 : 0, iso-C16 : 1 H, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 and iso-C14 : 0. The polar lipid profile included diphosphadidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, one unidentified glycophospholipid, two unidentified phospholipids and five unidentified lipids. The DNA G+C content was 74.2 mol%. DNA-DNA relatedness values between strain GP-S2-8T and type strains of the genus Blastococcus ranged from 14.6 to 48.6 %. On the basis of the phenotypic differences and DNA-DNA relatedness data, the isolate represents a new species of the genus Blastococcus, for which the name Blastococcuslitoris sp. nov. is proposed. The type strain is GP-S2-8T (=KCCM 43275T=JCM 32354T=DSM 106127T=KCTC 49078T).}, } @article {pmid30215594, year = {2018}, author = {Corral, P and de la Haba, RR and Infante-Domínguez, C and Sánchez-Porro, C and Amoozegar, MA and Papke, RT and Ventosa, A}, title = {Halorubrum chaoviator Mancinelli et al. 2009 is a later, heterotypic synonym of Halorubrum ezzemoulense Kharroub et al. 2006. Emended description of Halorubrum ezzemoulense Kharroub et al. 2006.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3657-3665}, doi = {10.1099/ijsem.0.003005}, pmid = {30215594}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Genes, Bacterial ; Halorubrum/*classification ; Lipids/chemistry ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A polyphasic comparative taxonomic study of Halorubrum ezzemoulense Kharroub et al. 2006, Halorubrum chaoviator Mancinelli et al. 2009 and eight new Halorubrum strains related to these haloarchaeal species was carried out. Multilocus sequence analysis using the five concatenated housekeeping genes atpB, EF-2, glnA, ppsA and rpoB', and phylogenetic analysis based on the 757 core protein sequences obtained from their genomes showed that Hrr. ezzemoulense DSM 17463T, Hrr. chaoviator Halo-G*T (=DSM 19316T) and the eight Halorubrum strains formed a robust cluster, clearly separated from the remaining species of the genus Halorubrum. The orthoANI value and digital DNA-DNA hybridization value, calculated by the Genome-to-Genome Distance Calculator (GGDC), showed percentages among Hrr. ezzemoulense DSM 17463T, Hrr. chaoviator DSM 19316T and the eight Halorubrum strains ranging from 99.4 to 97.9 %, and from 95.0 to 74.2 %, respectively, while these values for those strains and the type strains of the most closely related species of Halorubrum were 88.7-77.4 % and 36.1-22.3 %, respectively. Although some differences were observed, the phenotypic and polar lipid profiles were quite similar for all the strains studied. Overall, these data show that Hrr. ezzemoulense, Hrr. chaoviator and the eight new Halorubrum isolates constitute a single species. Thus, Hrr. chaoviator should be considered as a later, heterotypic synonym of Hrr. ezzemoulense. We propose an emended description of Hrr. ezzemoulense, including the features of Hrr. chaoviator and those of the eight new isolates.}, } @article {pmid30214716, year = {2018}, author = {Kahn, PC and Cao, DD and Burns, M and Boyer, SL}, title = {Nuptial gift chemistry reveals convergent evolution correlated with antagonism in mating systems of harvestmen (Arachnida, Opiliones).}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7103-7110}, pmid = {30214716}, issn = {2045-7758}, abstract = {Nuptial gifts are material donations given from male to female before or during copulation and are subject to sexual selection in a wide variety of taxa. The harvestman genus Leiobunum has emerged as a model system for understanding the evolution of reproductive morphology and behavior, as transitions between solicitous and antagonistic modes of courtship have occurred multiple times within the lineage and are correlated with convergence in genital morphology. We analyzed the free amino acid content of nuptial gift secretions from five species of Leiobunum using gas chromatography-mass spectrometry. Multivariate analysis of the free amino acid profiles revealed that, rather than clustering based on phylogenetic relationships, nuptial gift chemical composition was better predicted by genital morphology and behavior, suggesting that convergent evolution has acted on the chemical composition of the nuptial gift. In addition, we found that, species with solicitous courtship produce gifts consisting of a 19% larger proportion of essential amino acids as compared to those with more antagonistic courtship interactions. This work represents the first comparative study of nuptial gift chemistry within a phylogenetic framework in any animal group and as such contributes to our understanding of the evolution of reproductive diversity and the participant role of nuptial gift chemistry in mating system transitions.}, } @article {pmid30214032, year = {2018}, author = {Baker, J}, title = {Forgotten heroes of the Enigma story.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {307-308}, doi = {10.1038/d41586-018-06149-y}, pmid = {30214032}, issn = {1476-4687}, } @article {pmid30214022, year = {2018}, author = {Hofer, U}, title = {HIV-1's fingerprint.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {658-659}, doi = {10.1038/s41579-018-0086-0}, pmid = {30214022}, issn = {1740-1534}, } @article {pmid30213917, year = {2018}, author = {Bibic, L}, title = {Learning to lead.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1158}, doi = {10.1126/science.361.6407.1158}, pmid = {30213917}, issn = {1095-9203}, } @article {pmid30213916, year = {2018}, author = {Pryor, JM and Conlin, MP and Carvajal-Garcia, J and Luedeman, ME and Luthman, AJ and Small, GW and Ramsden, DA}, title = {Ribonucleotide incorporation enables repair of chromosome breaks by nonhomologous end joining.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1126-1129}, pmid = {30213916}, issn = {1095-9203}, support = {F31 CA203156/CA/NCI NIH HHS/United States ; R01 CA097096/CA/NCI NIH HHS/United States ; T32 GM007092/GM/NIGMS NIH HHS/United States ; T32 GM119999/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins ; CRISPR-Associated Protein 9 ; Cell Line ; *Chromosome Breakage ; Clustered Regularly Interspaced Short Palindromic Repeats ; *DNA End-Joining Repair ; *DNA Repair ; DNA-Directed DNA Polymerase/*metabolism ; Endonucleases ; Eosinophil-Derived Neurotoxin/genetics/metabolism ; Fibroblasts ; Genomic Instability ; Mice ; Ribonucleotides/*metabolism ; V(D)J Recombination ; }, abstract = {The nonhomologous end-joining (NHEJ) pathway preserves genome stability by ligating the ends of broken chromosomes together. It employs end-processing enzymes, including polymerases, to prepare ends for ligation. We show that two such polymerases incorporate primarily ribonucleotides during NHEJ-an exception to the central dogma of molecular biology-both during repair of chromosome breaks made by Cas9 and during V(D)J recombination. Moreover, additions of ribonucleotides but not deoxynucleotides effectively promote ligation. Repair kinetics suggest that ribonucleotide-dependent first-strand ligation is followed by complementary strand repair with deoxynucleotides, then by replacement of ribonucleotides embedded in the first strand with deoxynucleotides. Our results indicate that as much as 65% of cellular NHEJ products have transiently embedded ribonucleotides, which promote flexibility in repair at the cost of more fragile intermediates.}, } @article {pmid30213915, year = {2018}, author = {Yu, Q and Xue, L and Hiblot, J and Griss, R and Fabritz, S and Roux, C and Binz, PA and Haas, D and Okun, JG and Johnsson, K}, title = {Semisynthetic sensor proteins enable metabolic assays at the point of care.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1122-1126}, doi = {10.1126/science.aat7992}, pmid = {30213915}, issn = {1095-9203}, mesh = {*Bioluminescence Resonance Energy Transfer Techniques ; *Biosensing Techniques ; Blood Glucose/analysis ; Escherichia coli Proteins/*chemistry/genetics ; Glutamic Acid/blood ; Humans ; Monitoring, Physiologic/*methods ; NADP/metabolism ; Oxidation-Reduction ; Phenylalanine/blood ; Phenylketonurias/blood/diagnosis ; *Point-of-Care Testing ; Tetrahydrofolate Dehydrogenase/*chemistry/genetics ; }, abstract = {Monitoring metabolites at the point of care could improve the diagnosis and management of numerous diseases. Yet for most metabolites, such assays are not available. We introduce semisynthetic, light-emitting sensor proteins for use in paper-based metabolic assays. The metabolite is oxidized by nicotinamide adenine dinucleotide phosphate, and the sensor changes color in the presence of the reduced cofactor, enabling metabolite quantification with the use of a digital camera. The approach makes any metabolite that can be oxidized by the cofactor a candidate for quantitative point-of-care assays, as shown for phenylalanine, glucose, and glutamate. Phenylalanine blood levels of phenylketonuria patients were analyzed at the point of care within minutes with only 0.5 microliters of blood. Results were within 15% of those obtained with standard testing methods.}, } @article {pmid30213914, year = {2018}, author = {Hansen, KG and Aviram, N and Laborenz, J and Bibi, C and Meyer, M and Spang, A and Schuldiner, M and Herrmann, JM}, title = {An ER surface retrieval pathway safeguards the import of mitochondrial membrane proteins in yeast.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1118-1122}, doi = {10.1126/science.aar8174}, pmid = {30213914}, issn = {1095-9203}, mesh = {Electron Transport Complex IV/genetics/*metabolism ; Endoplasmic Reticulum/*metabolism ; Membrane Proteins/genetics/*metabolism ; Metabolic Networks and Pathways/genetics/physiology ; Mitochondria/genetics/*metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Molecular Chaperones/genetics/*metabolism ; Nuclear Proteins/genetics/*metabolism ; Protein Transport ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; }, abstract = {The majority of organellar proteins are translated on cytosolic ribosomes and must be sorted correctly to function. Targeting routes have been identified for organelles such as peroxisomes and the endoplasmic reticulum (ER). However, little is known about the initial steps of targeting of mitochondrial proteins. In this study, we used a genome-wide screen in yeast and identified factors critical for the intracellular sorting of the mitochondrial inner membrane protein Oxa1. The screen uncovered an unexpected path, termed ER-SURF, for targeting of mitochondrial membrane proteins. This pathway retrieves mitochondrial proteins from the ER surface and reroutes them to mitochondria with the aid of the ER-localized chaperone Djp1. Hence, cells use the expanse of the ER surfaces as a fail-safe to maximize productive mitochondrial protein targeting.}, } @article {pmid30213913, year = {2018}, author = {Van Doren, BM and Horton, KG}, title = {A continental system for forecasting bird migration.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1115-1118}, doi = {10.1126/science.aat7526}, pmid = {30213913}, issn = {1095-9203}, mesh = {Accident Prevention/*methods ; Altitude ; *Animal Migration ; Animals ; *Birds ; Environmental Monitoring/*methods ; Forecasting ; Seasons ; United States ; }, abstract = {Billions of animals cross the globe each year during seasonal migrations, but efforts to monitor them are hampered by the unpredictability of their movements. We developed a bird migration forecast system at a continental scale by leveraging 23 years of spring observations to identify associations between atmospheric conditions and bird migration intensity. Our models explained up to 81% of variation in migration intensity across the United States at altitudes of 0 to 3000 meters, and performance remained high in forecasting events 1 to 7 days in advance (62 to 76% of variation was explained). Avian migratory movements across the United States likely exceed 500 million individuals per night during peak passage. Bird migration forecasts will reduce collisions with buildings, airplanes, and wind turbines; inform a variety of monitoring efforts; and engage the public.}, } @article {pmid30213912, year = {2018}, author = {Toyota, M and Spencer, D and Sawai-Toyota, S and Jiaqi, W and Zhang, T and Koo, AJ and Howe, GA and Gilroy, S}, title = {Glutamate triggers long-distance, calcium-based plant defense signaling.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1112-1115}, doi = {10.1126/science.aat7744}, pmid = {30213912}, issn = {1095-9203}, mesh = {Animals ; Calcium/metabolism/*physiology ; *Calcium Signaling ; Glutamic Acid/metabolism/*physiology ; *Herbivory ; Phloem/metabolism ; *Plant Physiological Phenomena ; Plasmodesmata/metabolism ; Receptors, Glutamate/*physiology ; }, abstract = {Animals require rapid, long-range molecular signaling networks to integrate sensing and response throughout their bodies. The amino acid glutamate acts as an excitatory neurotransmitter in the vertebrate central nervous system, facilitating long-range information exchange via activation of glutamate receptor channels. Similarly, plants sense local signals, such as herbivore attack, and transmit this information throughout the plant body to rapidly activate defense responses in undamaged parts. Here we show that glutamate is a wound signal in plants. Ion channels of the GLUTAMATE RECEPTOR-LIKE family act as sensors that convert this signal into an increase in intracellular calcium ion concentration that propagates to distant organs, where defense responses are then induced.}, } @article {pmid30213911, year = {2018}, author = {Curtis, PG and Slay, CM and Harris, NL and Tyukavina, A and Hansen, MC}, title = {Classifying drivers of global forest loss.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1108-1111}, doi = {10.1126/science.aau3445}, pmid = {30213911}, issn = {1095-9203}, mesh = {Agriculture ; *Conservation of Natural Resources ; Forestry ; *Forests ; Satellite Imagery ; *Trees ; Wildfires ; }, abstract = {Global maps of forest loss depict the scale and magnitude of forest disturbance, yet companies, governments, and nongovernmental organizations need to distinguish permanent conversion (i.e., deforestation) from temporary loss from forestry or wildfire. Using satellite imagery, we developed a forest loss classification model to determine a spatial attribution of forest disturbance to the dominant drivers of land cover and land use change over the period 2001 to 2015. Our results indicate that 27% of global forest loss can be attributed to deforestation through permanent land use change for commodity production. The remaining areas maintained the same land use over 15 years; in those areas, loss was attributed to forestry (26%), shifting agriculture (24%), and wildfire (23%). Despite corporate commitments, the rate of commodity-driven deforestation has not declined. To end deforestation, companies must eliminate 5 million hectares of conversion from supply chains each year.}, } @article {pmid30213910, year = {2018}, author = {Wang, K and Titchener, JG and Kruk, SS and Xu, L and Chung, HP and Parry, M and Kravchenko, II and Chen, YH and Solntsev, AS and Kivshar, YS and Neshev, DN and Sukhorukov, AA}, title = {Quantum metasurface for multiphoton interference and state reconstruction.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1104-1108}, doi = {10.1126/science.aat8196}, pmid = {30213910}, issn = {1095-9203}, abstract = {Metasurfaces based on resonant nanophotonic structures have enabled innovative types of flat-optics devices that often outperform the capabilities of bulk components, yet these advances remain largely unexplored for quantum applications. We show that nonclassical multiphoton interferences can be achieved at the subwavelength scale in all-dielectric metasurfaces. We simultaneously image multiple projections of quantum states with a single metasurface, enabling a robust reconstruction of amplitude, phase, coherence, and entanglement of multiphoton polarization-encoded states. One- and two-photon states are reconstructed through nonlocal photon correlation measurements with polarization-insensitive click detectors positioned after the metasurface, and the scalability to higher photon numbers is established theoretically. Our work illustrates the feasibility of ultrathin quantum metadevices for the manipulation and measurement of multiphoton quantum states, with applications in free-space quantum imaging and communications.}, } @article {pmid30213909, year = {2018}, author = {Stav, T and Faerman, A and Maguid, E and Oren, D and Kleiner, V and Hasman, E and Segev, M}, title = {Quantum entanglement of the spin and orbital angular momentum of photons using metamaterials.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1101-1104}, doi = {10.1126/science.aat9042}, pmid = {30213909}, issn = {1095-9203}, abstract = {Metamaterials constructed from deep subwavelength building blocks have been used to demonstrate phenomena ranging from negative refractive index and ε-near-zero to cloaking, emulations of general relativity, and superresolution imaging. More recently, metamaterials have been suggested as a new platform for quantum optics. We present the use of a dielectric metasurface to generate entanglement between the spin and orbital angular momentum of photons. We demonstrate the generation of the four Bell states on a single photon by using the geometric phase that arises from the photonic spin-orbit interaction and subsequently show nonlocal correlations between two photons that interacted with the metasurface. Our results show that metamaterials are suitable for the generation and manipulation of entangled photon states, introducing the area of quantum optics metamaterials.}, } @article {pmid30213908, year = {2018}, author = {Mirts, EN and Petrik, ID and Hosseinzadeh, P and Nilges, MJ and Lu, Y}, title = {A designed heme-[4Fe-4S] metalloenzyme catalyzes sulfite reduction like the native enzyme.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1098-1101}, doi = {10.1126/science.aat8474}, pmid = {30213908}, issn = {1095-9203}, support = {R01 GM062211/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; *Biocatalysis ; Coenzymes/*chemistry ; Cytochrome-c Peroxidase/*chemistry ; Iron-Sulfur Proteins/*chemistry ; Oxidation-Reduction ; Protein Engineering ; Sulfites/*chemistry ; }, abstract = {Multielectron redox reactions often require multicofactor metalloenzymes to facilitate coupled electron and proton movement, but it is challenging to design artificial enzymes to catalyze these important reactions, owing to their structural and functional complexity. We report a designed heteronuclear heme-[4Fe-4S] cofactor in cytochrome c peroxidase as a structural and functional model of the enzyme sulfite reductase. The initial model exhibits spectroscopic and ligand-binding properties of the native enzyme, and sulfite reduction activity was improved-through rational tuning of the secondary sphere interactions around the [4Fe-4S] and the substrate-binding sites-to be close to that of the native enzyme. By offering insight into the requirements for a demanding six-electron, seven-proton reaction that has so far eluded synthetic catalysts, this study provides strategies for designing highly functional multicofactor artificial enzymes.}, } @article {pmid30213907, year = {2018}, author = {Karásek, M and Muijres, FT and De Wagter, C and Remes, BDW and de Croon, GCHE}, title = {A tailless aerial robotic flapper reveals that flies use torque coupling in rapid banked turns.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1089-1094}, doi = {10.1126/science.aat0350}, pmid = {30213907}, issn = {1095-9203}, mesh = {Acceleration ; Animals ; *Biological Mimicry ; Flight, Animal/*physiology ; *Robotics ; Tail ; Tephritidae/*physiology ; *Torque ; }, abstract = {Insects are among the most agile natural flyers. Hypotheses on their flight control cannot always be validated by experiments with animals or tethered robots. To this end, we developed a programmable and agile autonomous free-flying robot controlled through bio-inspired motion changes of its flapping wings. Despite being 55 times the size of a fruit fly, the robot can accurately mimic the rapid escape maneuvers of flies, including a correcting yaw rotation toward the escape heading. Because the robot's yaw control was turned off, we showed that these yaw rotations result from passive, translation-induced aerodynamic coupling between the yaw torque and the roll and pitch torques produced throughout the maneuver. The robot enables new methods for studying animal flight, and its flight characteristics allow for real-world flight missions.}, } @article {pmid30213906, year = {2018}, author = {Smith, KR and Woodward, A and Haines, A and Chafe, Z}, title = {Prioritizing population policies.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1082}, doi = {10.1126/science.aav3528}, pmid = {30213906}, issn = {1095-9203}, mesh = {*Population Dynamics ; *Public Policy ; }, } @article {pmid30213905, year = {2018}, author = {Lyons, PB and Kotek, JF}, title = {U.S. fast test reactor will pay dividends.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1081-1082}, doi = {10.1126/science.aau7786}, pmid = {30213905}, issn = {1095-9203}, } @article {pmid30213904, year = {2018}, author = {Demmer, R and Beschta, RL}, title = {Grazing limits benefited Bridge Creek.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1081}, doi = {10.1126/science.aau5005}, pmid = {30213904}, issn = {1095-9203}, mesh = {*Environmental Monitoring ; *Seasons ; }, } @article {pmid30213903, year = {2018}, author = {Beuse, M and Schmidt, TS and Wood, V}, title = {A "technology-smart" battery policy strategy for Europe.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1075-1077}, doi = {10.1126/science.aau2516}, pmid = {30213903}, issn = {1095-9203}, } @article {pmid30213902, year = {2018}, author = {Ruffier, F}, title = {Robotic-flapper maneuvers and fruitfly turns.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1073-1074}, doi = {10.1126/science.aau7350}, pmid = {30213902}, issn = {1095-9203}, mesh = {Animals ; Drosophila ; *Robotic Surgical Procedures ; *Robotics ; }, } @article {pmid30213901, year = {2018}, author = {Riva, R}, title = {Enantioselective four-component Ugi reactions.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1072-1073}, doi = {10.1126/science.aau7497}, pmid = {30213901}, issn = {1095-9203}, mesh = {Molecular Structure ; Stereoisomerism ; }, } @article {pmid30213900, year = {2018}, author = {Lancaster, KM}, title = {Revving up an artificial metalloenzyme.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1071-1072}, doi = {10.1126/science.aau7754}, pmid = {30213900}, issn = {1095-9203}, mesh = {*Metalloproteins ; }, } @article {pmid30213899, year = {2018}, author = {Modesti, M}, title = {A pinch of RNA spices up DNA repair.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1069-1070}, doi = {10.1126/science.aau9194}, pmid = {30213899}, issn = {1095-9203}, mesh = {DNA Repair ; Plant Extracts ; *RNA ; *Spices ; }, } @article {pmid30213898, year = {2018}, author = {Muday, GK and Brown-Harding, H}, title = {Nervous system-like signaling in plant defense.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1068-1069}, doi = {10.1126/science.aau9813}, pmid = {30213898}, issn = {1095-9203}, mesh = {Gene Expression Regulation, Plant ; Nervous System ; Plant Diseases ; Plant Proteins/genetics ; *Plants ; *Signal Transduction ; }, } @article {pmid30213897, year = {2018}, author = {Lenton, TM and Latour, B}, title = {Gaia 2.0.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1066-1068}, doi = {10.1126/science.aau0427}, pmid = {30213897}, issn = {1095-9203}, mesh = {*Biological Evolution ; *Earth (Planet) ; Humans ; *Nature ; Technology/*trends ; }, } @article {pmid30213896, year = {2018}, author = {Amandolare, S}, title = {Windfall.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1064-1065}, doi = {10.1126/science.361.6407.1064}, pmid = {30213896}, issn = {1095-9203}, mesh = {*Cyclonic Storms ; *Forests ; *Global Warming ; }, } @article {pmid30213895, year = {2018}, author = {Plautz, J}, title = {Piercing the haze.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1060-1063}, doi = {10.1126/science.361.6407.1060}, pmid = {30213895}, issn = {1095-9203}, mesh = {Air Pollutants/*analysis/standards/toxicity ; Air Pollution/*analysis ; Ammonia/*analysis/standards/toxicity ; *Farms ; Maryland ; Seasons ; Smog/*analysis ; Utah ; }, } @article {pmid30213894, year = {2018}, author = {Lawler, A}, title = {Scarred bird bones reveal early settlement on Madagascar.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1059}, doi = {10.1126/science.361.6407.1059}, pmid = {30213894}, issn = {1095-9203}, mesh = {Animals ; Archaeology ; *Birds ; Bone and Bones/*pathology ; *Cicatrix ; *Extinction, Biological ; Humans ; Madagascar ; }, } @article {pmid30213893, year = {2018}, author = {Voosen, P}, title = {NASA space laser targets melting poles.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1058}, doi = {10.1126/science.361.6407.1058}, pmid = {30213893}, issn = {1095-9203}, } @article {pmid30213892, year = {2018}, author = {Leslie, M}, title = {New cancer-fighting cells enter trials.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1056-1057}, doi = {10.1126/science.361.6407.1056}, pmid = {30213892}, issn = {1095-9203}, mesh = {Cell Engineering ; Clinical Trials as Topic ; Humans ; Immunotherapy/*methods ; Killer Cells, Natural/immunology/*transplantation ; Macrophages/immunology/*transplantation ; Neoplasms/*therapy ; Receptors, Antigen/analysis/genetics/immunology ; T-Lymphocytes/immunology/transplantation ; United States ; United States Food and Drug Administration ; }, } @article {pmid30213891, year = {2018}, author = {Cohen, J}, title = {Steep drop in Zika cases undermines vaccine trial.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1055-1056}, doi = {10.1126/science.361.6407.1055}, pmid = {30213891}, issn = {1095-9203}, mesh = {Brazil/epidemiology ; Clinical Trials as Topic ; Global Health ; Healthy Volunteers/statistics & numerical data ; Humans ; National Institute of Allergy and Infectious Diseases (U.S.) ; United States ; *Viral Vaccines ; Zika Virus/*immunology ; Zika Virus Infection/*epidemiology/*prevention & control ; }, } @article {pmid30213890, year = {2018}, author = {Cho, A}, title = {Physicists plan hunt for Higgs boson pairs.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1054-1055}, doi = {10.1126/science.361.6407.1054}, pmid = {30213890}, issn = {1095-9203}, } @article {pmid30213889, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1052-1053}, doi = {10.1126/science.361.6407.1052}, pmid = {30213889}, issn = {1095-9203}, } @article {pmid30213888, year = {2018}, author = {Baillie, J and Zhang, YP}, title = {Space for nature.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1051}, doi = {10.1126/science.aau1397}, pmid = {30213888}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; *Biomass ; *Earth (Planet) ; *Extinction, Biological ; Humans ; Population Dynamics ; }, } @article {pmid30213887, year = {2018}, author = {Reich, PB and Hobbie, SE and Lee, TD and Pastore, MA}, title = {Response to Comment on "Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {}, doi = {10.1126/science.aau8982}, pmid = {30213887}, issn = {1095-9203}, mesh = {Biomass ; *Carbon Dioxide ; Climate ; Climate Change ; *Poaceae ; }, abstract = {Nie and colleagues suggest a key role for interannual climate variation as an explanation for the temporal dynamics of an unexpected 20-year reversal of biomass responses of C3-C4 grasses to elevated CO2 However, we had already identified some climate-dependent differences in C3 and C4 responses to eCO2 and shown that these could not fully explain the temporal dynamics we observed.}, } @article {pmid30213886, year = {2018}, author = {Zhang, J and Yu, P and Li, SY and Sun, H and Xiang, SH and Wang, JJ and Houk, KN and Tan, B}, title = {Asymmetric phosphoric acid-catalyzed four-component Ugi reaction.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {}, doi = {10.1126/science.aas8707}, pmid = {30213886}, issn = {1095-9203}, abstract = {The Ugi reaction constructs α-acylaminoamide compounds by combining an aldehyde or ketone, an amine, a carboxylic acid, and an isocyanide in a single flask. Its appealing features include inherent atom and step economy together with the potential to generate products of broad structural diversity. However, control of the stereochemistry in this reaction has proven to be a formidable challenge. We describe an efficient enantioselective four-component Ugi reaction catalyzed by a chiral phosphoric acid derivative that delivers more than 80 α-acylaminoamides in good to excellent enantiomeric excess. Experimental and computational studies establish the reaction mechanism and origins of stereoselectivity.}, } @article {pmid30213885, year = {2018}, author = {Bolding, KA and Franks, KM}, title = {Recurrent cortical circuits implement concentration-invariant odor coding.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {}, doi = {10.1126/science.aat6904}, pmid = {30213885}, issn = {1095-9203}, support = {R01 DC015525/DC/NIDCD NIH HHS/United States ; K99 DC009839/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Feedback, Physiological ; Mice ; Odorants/analysis ; Olfactory Bulb/physiology ; Olfactory Pathways/*physiology ; *Olfactory Perception ; Piriform Cortex/*physiology ; Smell/*physiology ; }, abstract = {Animals rely on olfaction to find food, attract mates, and avoid predators. To support these behaviors, they must be able to identify odors across different odorant concentrations. The neural circuit operations that implement this concentration invariance remain unclear. We found that despite concentration-dependence in the olfactory bulb (OB), representations of odor identity were preserved downstream, in the piriform cortex (PCx). The OB cells responding earliest after inhalation drove robust responses in sparse subsets of PCx neurons. Recurrent collateral connections broadcast their activation across the PCx, recruiting global feedback inhibition that rapidly truncated and suppressed cortical activity for the remainder of the sniff, discounting the impact of slower, concentration-dependent OB inputs. Eliminating recurrent collateral output amplified PCx odor responses rendered the cortex steeply concentration-dependent and abolished concentration-invariant identity decoding.}, } @article {pmid30213884, year = {2018}, author = {DiToro, D and Winstead, CJ and Pham, D and Witte, S and Andargachew, R and Singer, JR and Wilson, CG and Zindl, CL and Luther, RJ and Silberger, DJ and Weaver, BT and Kolawole, EM and Martinez, RJ and Turner, H and Hatton, RD and Moon, JJ and Way, SS and Evavold, BD and Weaver, CT}, title = {Differential IL-2 expression defines developmental fates of follicular versus nonfollicular helper T cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {}, doi = {10.1126/science.aao2933}, pmid = {30213884}, issn = {1095-9203}, support = {T32 AI007051/AI/NIAID NIH HHS/United States ; F30 DK105680/DK/NIDDK NIH HHS/United States ; DP1 AI131080/AI/NIAID NIH HHS/United States ; R01 AI035783/AI/NIAID NIH HHS/United States ; R21 AI124143/AI/NIAID NIH HHS/United States ; T32 GM008361/GM/NIGMS NIH HHS/United States ; R01 AI110113/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/*immunology ; Chromatin/metabolism ; *Gene Expression ; Genes, Reporter ; Interleukin-2/*genetics ; Lymphocyte Activation/genetics ; Mice ; Mice, Transgenic ; Proto-Oncogene Proteins c-bcl-2/genetics ; Receptors, Antigen, T-Cell/genetics/*metabolism ; T-Lymphocytes, Helper-Inducer/*immunology ; Transcription Factors/metabolism ; }, abstract = {In response to infection, naïve CD4+ T cells differentiate into two subpopulations: T follicular helper (TFH) cells, which support B cell antibody production, and non-TFH cells, which enhance innate immune cell functions. Interleukin-2 (IL-2), the major cytokine produced by naïve T cells, plays an important role in the developmental divergence of these populations. However, the relationship between IL-2 production and fate determination remains unclear. Using reporter mice, we found that differential production of IL-2 by naïve CD4+ T cells defined precursors fated for different immune functions. IL-2 producers, which were fated to become TFH cells, delivered IL-2 to nonproducers destined to become non-TFH cells. Because IL-2 production was limited to cells receiving the strongest T cell receptor (TCR) signals, a direct link between TCR-signal strength, IL-2 production, and T cell fate determination has been established.}, } @article {pmid30213880, year = {2018}, author = {Ramrath, DJF and Niemann, M and Leibundgut, M and Bieri, P and Prange, C and Horn, EK and Leitner, A and Boehringer, D and Schneider, A and Ban, N}, title = {Evolutionary shift toward protein-based architecture in trypanosomal mitochondrial ribosomes.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6413}, pages = {}, doi = {10.1126/science.aau7735}, pmid = {30213880}, issn = {1095-9203}, mesh = {*Evolution, Molecular ; Mitochondrial Ribosomes/*chemistry/ultrastructure ; Models, Molecular ; Protozoan Proteins/*chemistry/ultrastructure ; RNA, Ribosomal/chemistry/ultrastructure ; Ribosomal Proteins/*chemistry/ultrastructure ; Trypanosoma brucei brucei/*ultrastructure ; }, abstract = {Ribosomal RNA (rRNA) plays key functional and architectural roles in ribosomes. Using electron microscopy, we determined the atomic structure of a highly divergent ribosome found in mitochondria of Trypanosoma brucei, a unicellular parasite that causes sleeping sickness in humans. The trypanosomal mitoribosome features the smallest rRNAs and contains more proteins than all known ribosomes. The structure shows how the proteins have taken over the role of architectural scaffold from the rRNA: They form an autonomous outer shell that surrounds the entire particle and stabilizes and positions the functionally important regions of the rRNA. Our results also reveal the "minimal" set of conserved rRNA and protein components shared by all ribosomes that help us define the most essential functional elements.}, } @article {pmid30213853, year = {2018}, author = {Singh, HP and Wang, S and Stachelek, K and Lee, S and Reid, MW and Thornton, ME and Craft, CM and Grubbs, BH and Cobrinik, D}, title = {Developmental stage-specific proliferation and retinoblastoma genesis in RB-deficient human but not mouse cone precursors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9391-E9400}, pmid = {30213853}, issn = {1091-6490}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; R01 CA137124/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Cell Division ; Humans ; Mice ; Mice, Knockout ; Retinal Cone Photoreceptor Cells/*metabolism/pathology ; Retinal Neoplasms/genetics/*metabolism/pathology ; Retinoblastoma/genetics/*metabolism/pathology ; Retinoblastoma Protein/*deficiency ; *S Phase ; Species Specificity ; }, abstract = {Most retinoblastomas initiate in response to the inactivation of the RB1 gene and loss of functional RB protein. The tumors may form with few additional genomic changes and develop after a premalignant retinoma phase. Despite this seemingly straightforward etiology, mouse models have not recapitulated the genetic, cellular, and stage-specific features of human retinoblastoma genesis. For example, whereas human retinoblastomas appear to derive from cone photoreceptor precursors, current mouse models develop tumors that derive from other retinal cell types. To investigate the basis of the human cone-specific oncogenesis, we compared developmental stage-specific cone precursor responses to RB loss in human and murine retina cultures and in cone-specific Rb1-knockout mice. We report that RB-depleted maturing (ARR3+) but not immature (ARR3-) human cone precursors enter the cell cycle, proliferate, and form retinoblastoma-like lesions with Flexner-Wintersteiner rosettes, then form low or nonproliferative premalignant retinoma-like lesions with fleurettes and p16INK4A and p130 expression, and finally form highly proliferative retinoblastoma-like masses. In contrast, in murine retina, only RB-depleted immature (Arr3-) cone precursors entered the cell cycle, and they failed to progress from S to M phase. Moreover, whereas intrinsically highly expressed MDM2 and MYCN contribute to RB-depleted maturing (ARR3+) human cone precursor proliferation, ectopic MDM2 and Mycn promoted only immature (Arr3-) murine cone precursor cell-cycle entry. These findings demonstrate that developmental stage-specific as well as species- and cell type-specific features sensitize to RB1 inactivation and reveal the human cone precursors' capacity to model retinoblastoma initiation, proliferation, premalignant arrest, and tumor growth.}, } @article {pmid30213852, year = {2018}, author = {Layer, JV and Cleary, JP and Brown, AJ and Stevenson, KE and Morrow, SN and Van Scoyk, A and Blasco, RB and Karaca, E and Meng, FL and Frock, RL and Tivey, T and Kim, S and Fuchs, H and Chiarle, R and Alt, FW and Roberts, SA and Weinstock, DM and Day, TA}, title = {Parp3 promotes long-range end joining in murine cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10076-10081}, pmid = {30213852}, issn = {1091-6490}, support = {R01 CA151898/CA/NCI NIH HHS/United States ; R01 CA172387/CA/NCI NIH HHS/United States ; }, mesh = {Anaplastic Lymphoma Kinase ; Animals ; B-Lymphocytes/*metabolism ; DNA End-Joining Repair/*physiology ; Fibroblasts/metabolism ; Immunoglobulin Class Switching/*physiology ; Mice ; Mouse Embryonic Stem Cells/*metabolism ; Oncogene Proteins, Fusion/genetics/metabolism ; Poly (ADP-Ribose) Polymerase-1/genetics/metabolism ; Poly(ADP-ribose) Polymerases/genetics/*metabolism ; Receptor Protein-Tyrosine Kinases/genetics/metabolism ; }, abstract = {Chromosomal rearrangements, including translocations, are early and essential events in the formation of many tumors. Previous studies that defined the genetic requirements for rearrangement formation have identified differences between murine and human cells, most notably in the role of classic and alternative nonhomologous end-joining (NHEJ) factors. We reported that poly(ADP)ribose polymerase 3 (PARP3) promotes chromosomal rearrangements induced by endonucleases in multiple human cell types. We show here that in contrast to classic (c-NHEJ) factors, Parp3 also promotes rearrangements in murine cells, including translocations in murine embryonic stem cells (mESCs), class-switch recombination in primary B cells, and inversions in tail fibroblasts that generate Eml4-Alk fusions. In mESCs, Parp3-deficient cells had shorter deletion lengths at translocation junctions. This was corroborated using next-generation sequencing of Eml4-Alk junctions in tail fibroblasts and is consistent with a role for Parp3 in promoting the processing of DNA double-strand breaks. We confirmed a previous report that Parp1 also promotes rearrangement formation. In contrast with Parp3, rearrangement junctions in the absence of Parp1 had longer deletion lengths, suggesting that Parp1 may suppress double-strand break processing. Together, these data indicate that Parp3 and Parp1 promote rearrangements with distinct phenotypes.}, } @article {pmid30213851, year = {2018}, author = {Ilca, FT and Neerincx, A and Wills, MR and de la Roche, M and Boyle, LH}, title = {Utilizing TAPBPR to promote exogenous peptide loading onto cell surface MHC I molecules.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9353-E9361}, pmid = {30213851}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; C14303/A17197//Cancer Research UK/United Kingdom ; MR/K021087/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Antigen Presentation ; HeLa Cells ; Histocompatibility Antigens Class I/genetics/*immunology ; Humans ; Immunity, Cellular ; Immunoglobulins/genetics/*immunology ; Interferon-gamma/genetics/immunology ; MCF-7 Cells ; Membrane Proteins/genetics/*immunology ; Mice ; Mice, Knockout ; Peptides/genetics/*immunology ; Receptors, Antigen, T-Cell/genetics/immunology ; T-Lymphocytes/immunology ; }, abstract = {The repertoire of peptides displayed at the cell surface by MHC I molecules is shaped by two intracellular peptide editors, tapasin and TAPBPR. While cell-free assays have proven extremely useful in identifying the function of both of these proteins, here we explored whether a more physiological system could be developed to assess TAPBPR-mediated peptide editing on MHC I. We reveal that membrane-associated TAPBPR targeted to the plasma membrane retains its ability to function as a peptide editor and efficiently catalyzes peptide exchange on surface-expressed MHC I molecules. Additionally, we show that soluble TAPBPR, consisting of the luminal domain alone, added to intact cells, also functions as an effective peptide editor on surface MHC I molecules. Thus, we have established two systems in which TAPBPR-mediated peptide exchange on MHC class I can be interrogated. Furthermore, we could use both plasma membrane-targeted and exogenous soluble TAPBPR to display immunogenic peptides on surface MHC I molecules and consequently induce T cell receptor engagement, IFN-γ secretion, and T cell-mediated killing of target cells. Thus, we have developed an efficient way to by-pass the natural antigen presentation pathway of cells and load immunogenic peptides of choice onto cells. Our findings highlight a potential therapeutic use for TAPBPR in increasing the immunogenicity of tumors in the future.}, } @article {pmid30213850, year = {2018}, author = {Mohren, TL and Daniel, TL and Brunton, SL and Brunton, BW}, title = {Neural-inspired sensors enable sparse, efficient classification of spatiotemporal data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10564-10569}, pmid = {30213850}, issn = {1091-6490}, mesh = {Animals ; Biomechanical Phenomena ; *Biomimetics ; Computer Simulation ; Flight, Animal/*physiology ; Insecta/*physiology ; Mechanoreceptors/*physiology ; *Models, Biological ; Orientation ; Rotation ; Spatio-Temporal Analysis ; Wings, Animal/*physiology ; }, abstract = {Sparse sensor placement is a central challenge in the efficient characterization of complex systems when the cost of acquiring and processing data is high. Leading sparse sensing methods typically exploit either spatial or temporal correlations, but rarely both. This work introduces a sparse sensor optimization that is designed to leverage the rich spatiotemporal coherence exhibited by many systems. Our approach is inspired by the remarkable performance of flying insects, which use a few embedded strain-sensitive neurons to achieve rapid and robust flight control despite large gust disturbances. Specifically, we identify neural-inspired sensors at a few key locations on a flapping wing that are able to detect body rotation. This task is particularly challenging as the rotational twisting mode is three orders of magnitude smaller than the flapping modes. We show that nonlinear filtering in time, built to mimic strain-sensitive neurons, is essential to detect rotation, whereas instantaneous measurements fail. Optimized sparse sensor placement results in efficient classification with approximately 10 sensors, achieving the same accuracy and noise robustness as full measurements consisting of hundreds of sensors. Sparse sensing with neural-inspired encoding establishes an alternative paradigm in hyperefficient, embodied sensing of spatiotemporal data and sheds light on principles of biological sensing for agile flight control.}, } @article {pmid30213708, year = {2018}, author = {Markus, MB}, title = {New Evidence for Hypnozoite-Independent Plasmodium vivax Malarial Recurrences.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1015-1016}, doi = {10.1016/j.pt.2018.08.010}, pmid = {30213708}, issn = {1471-5007}, abstract = {Information provided in recent, related papers has wide-ranging implications concerning, inter alia, the transmission of malaria, drug treatment, and eradication of the disease. Additionally, the research results represent support for the idea that recurrences of Plasmodium vivax malaria can arise from both liver hypnozoites and extravascular merozoites in bone marrow.}, } @article {pmid30213660, year = {2018}, author = {Doubleday, ZA and Connell, SD}, title = {Let Scientific Writing Evolve, Not Stagnate.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {812-813}, doi = {10.1016/j.tree.2018.08.008}, pmid = {30213660}, issn = {1872-8383}, } @article {pmid30213659, year = {2018}, author = {Costello, MJ and Horton, T and Kroh, A}, title = {Sustainable Biodiversity Databasing: International, Collaborative, Dynamic, Centralised.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {11}, pages = {803-805}, doi = {10.1016/j.tree.2018.08.006}, pmid = {30213659}, issn = {1872-8383}, abstract = {The World Register of Marine Species (WoRMS) is a sustainable model of international collaboration around a centralised database that provides expert validated biodiversity data freely online. This model could be replicated for the over 1.2 million terrestrial and freshwater species to improve quality control and data management in biology and ecology globally.}, } @article {pmid30213658, year = {2018}, author = {Godet, L and Devictor, V}, title = {What Conservation Does.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {720-730}, doi = {10.1016/j.tree.2018.07.004}, pmid = {30213658}, issn = {1872-8383}, abstract = {New agendas for conservation are regularly proposed based on the ground that existing strategies are overly pessimistic, restricted to biodiversity hotspots, and inappropriate to halt biodiversity loss. However, little empirical evidence supports such claims. Here we review the 12971 papers published in the leading conservation journals during the last 15 years to assess what conservation actually does. Although conservation research is affected by specific bias, conservation is playing a major role in providing empirical evidence of human impacts on biodiversity. Encouraging biodiversity comebacks are also published and a wide range of conservation tools, beyond the development of protected areas in wilderness areas, are promoted. We argue that finding new routes to conservation is neither necessary nor sufficient to halt biodiversity loss.}, } @article {pmid30213539, year = {2018}, author = {Liro, MJ and Morton, DG and Rose, LS}, title = {The kinases PIG-1 and PAR-1 act in redundant pathways to regulate asymmetric division in the EMS blastomere of C. elegans.}, journal = {Developmental biology}, volume = {444}, number = {1}, pages = {9-19}, pmid = {30213539}, issn = {1095-564X}, support = {R01 GM068744/GM/NIGMS NIH HHS/United States ; R01 GM079112/GM/NIGMS NIH HHS/United States ; }, abstract = {The PAR-1 kinase of C. elegans is localized to the posterior of the one-cell embryo and its mutations affect asymmetric spindle placement and partitioning of cytoplasmic components in the first cell cycle. However, par-1 mutations do not cause failure to restrict the anterior PAR polarity complex to the same extent as mutations in the posteriorly localized PAR-2 protein. Further, it has been difficult to examine the role of PAR-1 in subsequent divisions due to the early defects in par-1 mutant embryos. Here we show that the PIG-1 kinase acts redundantly with PAR-1 to restrict the anterior PAR-3 protein for normal polarity in the one-cell embryo. By using a temperature sensitive allele of par-1, which exhibits enhanced lethality when combined with a pig-1 mutation, we have further explored roles for these genes in subsequent divisions. We find that both PIG-1 and PAR-1 regulate spindle orientation in the EMS blastomere of the four-cell stage embryo to ensure that it undergoes an asymmetric division. In this cell, PIG-1 and PAR-1 act in parallel pathways for spindle positioning, PIG-1 in the MES-1/SRC-1 pathway and PAR-1 in the Wnt pathway.}, } @article {pmid30213538, year = {2018}, author = {Suzuki, M and Hayashi, T and Inoue, T and Agata, K and Hirayama, M and Suzuki, M and Shigenobu, S and Takeuchi, T and Yamamoto, T and Suzuki, KT}, title = {Cas9 ribonucleoprotein complex allows direct and rapid analysis of coding and noncoding regions of target genes in Pleurodeles waltl development and regeneration.}, journal = {Developmental biology}, volume = {443}, number = {2}, pages = {127-136}, doi = {10.1016/j.ydbio.2018.09.008}, pmid = {30213538}, issn = {1095-564X}, mesh = {Animals ; Animals, Genetically Modified ; Breeding/methods ; CRISPR-Associated Protein 9/*genetics/metabolism ; CRISPR-Cas Systems ; Developmental Biology/methods ; Gene Knockout Techniques ; Phenotype ; Pleurodeles/*genetics/metabolism ; Regeneration/*genetics ; Ribonucleoproteins/genetics/metabolism ; Sequence Analysis, DNA/methods ; }, abstract = {Newts have remarkable ability to regenerate their organs and have been used in research for centuries. However, the laborious work of breeding has hampered reverse genetics strategies in newt. Here, we present simple and efficient gene knockout using Cas9 ribonucleoprotein complex (RNP) in Pleurodeles waltl, a species suitable for regenerative biology studies using reverse genetics. Most of the founders exhibited severe phenotypes against each target gene (tyrosinase, pax6, tbx5); notably, all tyrosinase Cas9 RNP-injected embryos showed complete albinism. Moreover, amplicon sequencing analysis of Cas9 RNP-injected embryos revealed virtually complete biallelic disruption at target loci in founders, allowing direct phenotype analysis in the F0 generation. In addition, we demonstrated the generation of tyrosinase null F1 offspring within a year. Finally, we expanded this approach to the analysis of noncoding regulatory elements by targeting limb-specific enhancer of sonic hedgehog, known as the zone of polarizing activity regulatory sequence (ZRS; also called MFCS1). Disruption of ZRS led to digit deformation in limb regeneration. From these results, we are confident that this highly efficient gene knockout method will accelerate gene functional analysis in the post-genome era of salamanders.}, } @article {pmid30213537, year = {2018}, author = {Cima, F}, title = {Spermatogenesis as a tool for staging gonad development in the gonochoric appendicularian Oikopleura dioica Fol 1872.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.09.004}, pmid = {30213537}, issn = {1095-564X}, abstract = {Oikopleura dioica, the only gonochoric species among appendicularians, has a spematozoon with a mid-piece and a conspicuous acrosome that, during fertilisation, undergoes a reaction forming an acrosomal process. To provide more insight into the spermatogenesis of a holoplanktonic tunicate species that completes its life cycle in three to five days, changes in the testis during individual growth have been examined. Spermatogenesis has been subdivided into seven stages based on ultrastructural features during the formation and organisation of the male gonad and the relationships between its macroscopic anatomy and the events of sperm differentiation. Gametes undergo highly synchronised differentiation due to the presence of widespread syncytial structures. Both meiosis and spermiogenesis are brief, and the passage from spermatocytes to spermatids involves a progressive segregation of the germ cells from the syncytial mass with the formation of large cytoplasmic bridges and volume reduction for nucleus compacting and cytoplasmic material changing. The nucleus is small and penetrated anteriorly by a complex acrosome and posteriorly by the distal centriole and part of the flagellum. In spermatids, the single, large mitochondrion appears laterally to the nucleus, and finally, in spermatozoa, it migrates into the mid-piece, wrapping the proximal portion of the axoneme. Because this mitochondrial position is reached only in the late phases of spermatogenesis, it suggests that appendicularians have derived oligopyrenic sperms in which the small nucleus results from adaptation to the assembly of numerous spermatozoa inside the narrow space of the testis compacted in the genital cavity. The formulation of a staging system of gonad development in a model tunicate species known for having the most compacted genome in chordates led to a comparison of histological observations with recent molecular data, improving the characterisation of its biology and life cycle in light of evolutionary implications.}, } @article {pmid30213362, year = {2018}, author = {Efroni, I and Prasad, K}, title = {Insights into the art of recreation.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {1-2}, doi = {10.1016/j.ydbio.2018.08.007}, pmid = {30213362}, issn = {1095-564X}, mesh = {*Plant Development ; Plants ; Regeneration/*physiology ; Stem Cells ; }, } @article {pmid30213274, year = {2018}, author = {Huang, F and Ben Aissa, M and Lévesque, G and Carreau, M}, title = {FANCC localizes with UNC5A at neurite outgrowth and promotes neuritogenesis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {662}, pmid = {30213274}, issn = {1756-0500}, mesh = {Animals ; Cell Differentiation ; Fanconi Anemia ; Fanconi Anemia Complementation Group C Protein/*physiology ; Mice ; Mice, Knockout ; Netrin Receptors/*physiology ; *Neuronal Outgrowth ; Proteins ; }, abstract = {OBJECTIVE: The Uncoordinated 5A (UNC5A) protein is part of a family of receptors that play roles in axonal pathfinding and cell migration. We previously showed that the Fanconi anemia C protein (FANCC) interacts with UNC5A and delays UNC5A-mediated apoptosis. FANCC is a predominantly cytoplasmic protein that has multiple functions including DNA damage signaling, oxygen radical metabolism, signal transduction, transcriptional regulation and apoptosis. Given the direct interaction between FANCC and UNC5A and that FANCC interferes with UNC5A-mediated apoptosis, we explored the possibility that FANCC might play a role in axonal-like growth processes.

RESULTS: Here we show that FANCC and UNC5A are localized to regions of neurite outgrowth during neuronal cell differentiation. We also show that absence of FANCC is required for neurite outgrowth. In addition, FANCC seems required for UNC5A expression. Results from this study combined with our previous report suggest that FANCC plays a role in tissue development through the regulation of UNC5A-mediated functions.}, } @article {pmid30213259, year = {2018}, author = {Moolhuijzen, P and See, PT and Hane, JK and Shi, G and Liu, Z and Oliver, RP and Moffat, CS}, title = {Correction to: Comparative genomics of the wheat fungal pathogen Pyrenophora tritici-repentis reveals chromosomal variations and genome plasticity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {673}, pmid = {30213259}, issn = {1471-2164}, abstract = {ᅟ.}, } @article {pmid30212897, year = {2018}, author = {Cotton, TA}, title = {Arbuscular mycorrhizal fungal communities and global change: an uncertain future.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy179}, pmid = {30212897}, issn = {1574-6941}, abstract = {Arbuscular mycorrhizal (AM) fungi are amongst the most common and functionally important symbionts of terrestrial plants and are highly likely to be affected by global change. The potential consequences of this on plant growth and carbon and nutrient cycling has led to a growing demand for their inclusion in global change models. However, our understanding of their responses to environmental change remains limited. This review provides an overview of recent experiments attempting to predict the effects of atmospheric and climatic change on AM fungal community diversity, composition and functioning. This includes rising atmospheric carbon dioxide and tropospheric ozone levels, altered water availability, warming and nitrogen deposition. Changes detected are often highly variable and context dependent, but trends are emerging such as the similar responses of community composition to enhanced nitrogen deposition and atmospheric CO2, despite the likely contrasting effects of these environmental changes on carbon availability. The review also highlights shortfalls in our current knowledge and suggests priorities for future research, particularly advocating more integrated approaches linking the study of community characteristics and functions and examination of fine level genetic changes, wider geographical contexts and a greater range of AM fungal functions.}, } @article {pmid30212810, year = {2018}, author = {Cardilini, APA and Micallef, S and Bishop, VR and Sherman, CDH and Meddle, SL and Buchanan, KL}, title = {Environmental Influences on Neuromorphology in the Non-Native Starling Sturnus vulgaris.}, journal = {Brain, behavior and evolution}, volume = {92}, number = {1-2}, pages = {63-70}, doi = {10.1159/000491672}, pmid = {30212810}, issn = {1421-9743}, abstract = {Cognitive traits are predicted to be under intense selection in animals moving into new environments and may determine the success, or otherwise, of dispersal and invasions. In particular, spatial information related to resource distribution is an important determinant of neural development. Spatial information is predicted to vary for invasive species encountering novel environments. However, few studies have tested how cognition or neural development varies intraspecifically within an invasive species. In Australia, the non-native common starling Sturnus vulgaris inhabits a range of habitats that vary in seasonal resource availability and distribution. We aimed to identify variations in the brain mass and hippocampus volume of starlings in Australia related to environmental variation across two substantially different habitat types. Specifically, we predicted variation in brain mass and hippocampal volume in relation to environmental conditions, latitude, and climatic variables. To test this, brain mass and volumes of the hippocampus and two control brain regions (telencephalon and tractus septomesencephalicus) were quantified from starling brains gathered from across the species' range in south eastern Australia. When comparing across an environmental gradient, there was a significant interaction between sex and environment for overall brain mass, with greater sexual dimorphism in brain mass in inland populations compared to those at the coast. There was no significant difference in hippocampal volume in relation to environmental measures (hippocampus volume, n = 17) for either sex. While these data provide no evidence for intraspecific environmental drivers for changes in hippocampus volume in European starlings in Australia, they do suggest that environmental factors contribute to sex differences in brain mass. This study identifies associations between the brain volume of a non-native species and the environment; further work in this area is required to elucidate the mechanisms driving this relationship.}, } @article {pmid30212260, year = {2019}, author = {Santoro, AE and Richter, RA and Dupont, CL}, title = {Planktonic Marine Archaea.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {131-158}, doi = {10.1146/annurev-marine-121916-063141}, pmid = {30212260}, issn = {1941-0611}, abstract = {Archaea are ubiquitous and abundant members of the marine plankton. Once thought of as rare organisms found in exotic extremes of temperature, pressure, or salinity, archaea are now known in nearly every marine environment. Though frequently referred to collectively, the planktonic archaea actually comprise four major phylogenetic groups, each with its own distinct physiology and ecology. Only one group-the marine Thaumarchaeota-has cultivated representatives, making marine archaea an attractive focus point for the latest developments in cultivation-independent molecular methods. Here, we review the ecology, physiology, and biogeochemical impact of the four archaeal groups using recent insights from cultures and large-scale environmental sequencing studies. We highlight key gaps in our knowledge about the ecological roles of marine archaea in carbon flow and food web interactions. We emphasize the incredible uncultivated diversity within each of the four groups, suggesting there is much more to be done.}, } @article {pmid30212259, year = {2019}, author = {Gruber, N and Landschützer, P and Lovenduski, NS}, title = {The Variable Southern Ocean Carbon Sink.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {159-186}, doi = {10.1146/annurev-marine-121916-063407}, pmid = {30212259}, issn = {1941-0611}, abstract = {The CO2 uptake by the Southern Ocean (<35°S) varies substantially on all timescales and is a major determinant of the variations of the global ocean carbon sink. Particularly strong are the decadal changes characterized by a weakening period of the Southern Ocean carbon sink in the 1990s and a rebound after 2000. The weakening in the 1990s resulted primarily from a southward shift of the westerlies that enhanced the upwelling and outgassing of respired (i.e., natural) CO2. The concurrent reduction in the storage rate of anthropogenic CO2 in the mode and intermediate waters south of 35°S suggests that this shift also decreased the uptake of anthropogenic CO2. The rebound and the subsequent strong, decade-long reinvigoration of the carbon sink appear to have been driven by cooling in the Pacific Ocean, enhanced stratification in the Atlantic and Indian Ocean sectors, and a reduced overturning. Current-generation ocean models generally do not reproduce these variations and are poorly skilled at making decadal predictions in this region.}, } @article {pmid30212237, year = {2018}, author = {Cameron, S and McAllister, AK}, title = {Immunoglobulin-Like Receptors and Their Impact on Wiring of Brain Synapses.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {567-590}, doi = {10.1146/annurev-genet-120417-031513}, pmid = {30212237}, issn = {1545-2948}, abstract = {Synapse formation is mediated by a surprisingly large number and wide variety of genes encoding many different protein classes. One of the families increasingly implicated in synapse wiring is the immunoglobulin superfamily (IgSF). IgSF molecules are by definition any protein containing at least one Ig-like domain, making this family one of the most common protein classes encoded by the genome. Here, we review the emerging roles for IgSF molecules in synapse formation specifically in the vertebrate brain, focusing on examples from three classes of IgSF members: (a) cell adhesion molecules, (b) signaling molecules, and (c) immune molecules expressed in the brain. The critical roles for IgSF members in regulating synapse formation may explain their extensive involvement in neuropsychiatric and neurodevelopmental disorders. Solving the IgSF code for synapse formation may reveal multiple new targets for rescuing IgSF-mediated deficits in synapse formation and, eventually, new treatments for psychiatric disorders caused by altered IgSF-induced synapse wiring.}, } @article {pmid30212236, year = {2018}, author = {Zhang, L and Vijg, J}, title = {Somatic Mutagenesis in Mammals and Its Implications for Human Disease and Aging.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {397-419}, doi = {10.1146/annurev-genet-120417-031501}, pmid = {30212236}, issn = {1545-2948}, abstract = {DNA mutations as a consequence of errors during DNA damage repair, replication, or mitosis are the substrate for evolution. In multicellular organisms, mutations can occur in the germline and also in somatic tissues, where they are associated with cancer and other chronic diseases and possibly with aging. Recent advances in high-throughput sequencing have made it relatively easy to study germline de novo mutations, but in somatic cells, the vast majority of mutations are low-abundant and can be detected only in clonal lineages, such as tumors, or single cells. Here we review recent results on somatic mutations in normal human and animal tissues with a focus on their possible functional consequences.}, } @article {pmid30211971, year = {2018}, author = {Trapanese, C and Meunier, H and Masi, S}, title = {What, where and when: spatial foraging decisions in primates.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12462}, pmid = {30211971}, issn = {1469-185X}, support = {//Ethoikos foundation/ ; //Muséum National d'Histoire Naturelle de Paris and the Centre de Primatologie de l'Université de Strasbourg/ ; }, abstract = {When exploiting the environment, animals have to discriminate, track, and integrate salient spatial cues to navigate and identify goal sites. Actually, they have to know what can be found (e.g. what fruit), where (e.g. on which tree) and when (in what season or moment of the year). This is very relevant for primate species as they often live in seasonal and relatively unpredictable environments such as tropical forests. Here, we review and compare different approaches used to investigate primate spatial foraging strategies: from direct observations of wild primates to predictions from statistical simulations, including experimental approaches on both captive and wild primates, and experiments in captivity using virtual reality technology. Within this framework, most of these studies converge to show that many primate species can (i) remember the location of most of food resources well, and (ii) often seem to have a goal-oriented path towards spatially permanent resources. Overall, primates likely use mental maps to plan different foraging strategies to enhance their fitness. The majority of studies suggest that they may organise spatial information on food resources into topological maps: they use landmarks to navigate and encode local spatial information with regard to direction and distance. Even though these studies were able to show that primates can remember food quality (what) and its location (where), still very little is known on how they incorporate the temporal knowledge of available food (when). Future studies should attempt to increase our understanding of the potential of primates to learn temporal patterns and how both socio-ecological differences among species and their cognitive abilities influence such behavioural strategies.}, } @article {pmid30210800, year = {2018}, author = {Bailey, ES and Choi, JY and Fieldhouse, JK and Borkenhagen, LK and Zemke, J and Zhang, D and Gray, GC}, title = {The continual threat of influenza virus infections at the human-animal interface: What is new from a one health perspective?.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {192-198}, pmid = {30210800}, issn = {2050-6201}, abstract = {This year, in 2018, we mark 100 years since the 1918 influenza pandemic. In the last 100 years, we have expanded our knowledge of public health and increased our ability to detect and prevent influenza; however, we still face challenges resulting from these continually evolving viruses. Today, it is clear that influenza viruses have multiple animal reservoirs (domestic and wild), making infection prevention in humans especially difficult to achieve. With this report, we summarize new knowledge regarding influenza A, B, C and D viruses and their control. We also introduce how a multi-disciplinary One Health approach is necessary to mitigate these threats.}, } @article {pmid30210232, year = {2018}, author = {Silveira, MC and Azevedo da Silva, R and Faria da Mota, F and Catanho, M and Jardim, R and R Guimarães, AC and de Miranda, AB}, title = {Systematic Identification and Classification of β-Lactamases Based on Sequence Similarity Criteria: β-Lactamase Annotation.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318797351}, pmid = {30210232}, issn = {1176-9343}, abstract = {β-lactamases, the enzymes responsible for resistance to β-lactam antibiotics, are widespread among prokaryotic genera. However, current β-lactamase classification schemes do not represent their present diversity. Here, we propose a workflow to identify and classify β-lactamases. Initially, a set of curated sequences was used as a model for the construction of profiles Hidden Markov Models (HMM), specific for each β-lactamase class. An extensive, nonredundant set of β-lactamase sequences was constructed from 7 different resistance proteins databases to test the methodology. The profiles HMM were improved for their specificity and sensitivity and then applied to fully assembled genomes. Five hierarchical classification levels are described, and a new class of β-lactamases with fused domains is proposed. Our profiles HMM provide a better annotation of β-lactamases, with classes and subclasses defined by objective criteria such as sequence similarity. This classification offers a solid base to the elaboration of studies on the diversity, dispersion, prevalence, and evolution of the different classes and subclasses of this critical enzymatic activity.}, } @article {pmid30209883, year = {2018}, author = {Chase, AB and Gomez-Lunar, Z and Lopez, AE and Li, J and Allison, SD and Martiny, AC and Martiny, JBH}, title = {Emergence of soil bacterial ecotypes along a climate gradient.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4112-4126}, doi = {10.1111/1462-2920.14405}, pmid = {30209883}, issn = {1462-2920}, support = {DE-PS02-09ER09-25 DE-SC0016410//Biological and Environmental Research/ ; DEB-1457160//Division of Environmental Biology/ ; GM-69337//National Institute of General Medical Sciences/ ; Graduate Assistance of National Need (GAANN)//Office of Postsecondary Education/ ; //University of California Institute for Mexico and the United States/ ; DE-SC0016410//US Department of Energy Office of Science, Biological and Environmental Research/ ; DE-PS02-09ER09-25//US Department of Energy Office of Science, Biological and Environmental Research/ ; DEB-1457160//National Science Foundation/ ; GM-69337//National Institutes of Health Maximizing Access to Research Careers (MARC)/ ; //UC MEXUS-CONACYT/ ; //US Department of Education Graduate Assistance of National Need (GAANN)/ ; }, abstract = {The high diversity of soil bacteria is attributed to the spatial complexity of soil systems, where habitat heterogeneity promotes niche partitioning among bacterial taxa. This premise remains challenging to test, however, as it requires quantifying the traits of closely related soil bacteria and relating these traits to bacterial abundances and geographic distributions. Here, we sought to investigate whether the widespread soil taxon Curtobacterium consists of multiple coexisting ecotypes with differential geographic distributions. We isolated Curtobacterium strains from six sites along a climate gradient and assayed four functional traits that may contribute to niche partitioning in leaf litter, the top layer of soil. Our results revealed that cultured isolates separated into fine-scale genetic clusters that reflected distinct suites of phenotypic traits, denoting the existence of multiple ecotypes. We then quantified the distribution of Curtobacterium by analysing metagenomic data collected across the gradient over 18 months. Six abundant ecotypes were observed with differential abundances along the gradient, suggesting fine-scale niche partitioning. However, we could not clearly explain observed geographic distributions of ecotypes by relating their traits to environmental variables. Thus, while we can resolve soil bacterial ecotypes, the traits delineating their distinct niches in the environment remain unclear.}, } @article {pmid30209877, year = {2018}, author = {Fernández-González, AJ and Valette, N and Kohler, A and Dumarçay, S and Sormani, R and Gelhaye, E and Morel-Rouhier, M}, title = {Oak extractive-induced stress reveals the involvement of new enzymes in the early detoxification response of Phanerochaete chrysosporium.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3890-3901}, doi = {10.1111/1462-2920.14409}, pmid = {30209877}, issn = {1462-2920}, support = {ANR-11-LABX-0002-01//LABEX ARBRE/ ; ANR-11-LABX-0002-01//French National Research Agency/ ; }, abstract = {Extensive evidence showed that the efficiency of fungal wood degradation is closely dependent on their ability to cope with the myriad of putative toxic compounds called extractives released during this process. By analysing global gene expression of Phanerochaete chrysosporium after short oak extractive treatment (1, 3 and 6 h), we show that the early molecular response of the fungus concerns first mitochondrial stress rescue followed by the oxidation and finally conjugation of the compounds. During these early responses, the lignolytic degradative system is not induced, rather some small secreted proteins could play an important role in cell protection or signaling. By focusing on the functional characterization of an hitherto uncharacterized glutathione transferase, we show that this enzyme interacts with wood molecules suggesting that it could be involved in the detoxification of some of them, or act as a scavenger to prevent their cytosolic toxicity and favour their transport.}, } @article {pmid30209872, year = {2018}, author = {Pérez-Pantoja, D and Kim, J and Platero, R and de Lorenzo, V}, title = {The interplay of EIIANtr with C-source regulation of the Pu promoter of Pseudomonas putida mt-2.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4555-4566}, doi = {10.1111/1462-2920.14410}, pmid = {30209872}, issn = {1462-2920}, support = {B2017//Comunidad de Madrid/ ; H2020-FET-OPEN-RIA-2017-1-766975//Comunidad de Madrid/ ; H2020-BIOTEC-2014-2015-6335536//Comunidad de Madrid/ ; }, abstract = {The presence of some sugars (e.g. glucose) downregulates the activity of the Pu promoter of plasmid pWW0 of Pseudomonas putida mt-2, which drives the upper TOL operon for biodegradation of m-xylene. Genetic evidence produced 20 years ago documented an effect of the EIIANtr (PtsN) protein of the nitrogen-related phosphoenolpyruvate-dependent phosphotransferase system (PTSNtr) in such a C-source control of Pu activity. In this study, we have exploited the wealth of recent information on the PTS of P. putida as well as transcriptomic data available in the last few years on this bacterium to revisit this question - and the role of EIIANtr as such. To this end, we examined Pu output under physiological conditions known to either phosphorylate PTS proteins to saturation or to deplete them altogether from high-energy phosphate. The results showed that Pu activity is checked by EIIANtr regardless of its phosphorylation state. However, such inhibition is intensified during growth on glucose (which correlates with more phosphate-free EIIANtr) and partially relieved in fructose, which triggers phosphorylation of PTS proteins. These data explain former inconsistencies on the Pu-PTSNtr interplay and provides a better understanding of the metabolic and regulatory retroactivity between the TOL plasmid and its host metabolism.}, } @article {pmid30209867, year = {2018}, author = {Zhuang, GC and Peña-Montenegro, TD and Montgomery, A and Hunter, KS and Joye, SB}, title = {Microbial metabolism of methanol and methylamine in the Gulf of Mexico: insight into marine carbon and nitrogen cycling.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4543-4554}, doi = {10.1111/1462-2920.14406}, pmid = {30209867}, issn = {1462-2920}, support = {ECOGIG-2 Consortium//Gulf of Mexico Research Iniative/ ; //Gulf of Mexico Research Initiative/ ; }, abstract = {One carbon (C1) metabolism plays an important role in marine carbon cycling but the dynamics and modes of C1 transformations are not fully understood. We made contemporaneous measurements of methylamine and methanol metabolism to elucidate the role of C1 compounds as sources of carbon, energy and nitrogen. Methanol and methylamine were predominantly used as an energy source in offshore waters (oxidation rate constant: kmethanol : 0.02-0.10 day-1 ; kmethylamine : 0.01-0.18 day-1), but were also important sources of biomass carbon in coastal waters (assimilation rate constant: kmethanol : 0.04-0.10 day-1 ; kmethylamine : 0.01-0.05 day-1). The relative extent of assimilation versus oxidation for these substrates correlated positively with chlorophyll, nutrients and heterotrophic bacterial production. Methanol oxidation and assimilation were stimulated significantly by nutrient addition. In contrast, methylamine metabolism was inhibited by ammonium or nitrate, suggesting that methylamine served as a nitrogen source. A preliminary metagenomic survey revealed a diverse population of putative C1-utilizing microorganisms. These results show that the remineralization of methylamine could provide both C and N sources for microbes. Both methanol and methylamine contribute to microbial energetic and carbon substrate demands with a distinctly different signature in nearshore versus offshore environments.}, } @article {pmid30209866, year = {2018}, author = {Mangot, JF and Forn, I and Obiol, A and Massana, R}, title = {Constant abundances of ubiquitous uncultured protists in the open sea assessed by automated microscopy.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3876-3889}, doi = {10.1111/1462-2920.14408}, pmid = {30209866}, issn = {1462-2920}, support = {CSD2008-00077CTM2013-43767-PCTM2016-75083-R//Consejo Superior de Investigaciones Científicas/ ; CSIC15-EE-5379//European Regional Development Fund/ ; PIEF-GA-2012-331190//FP7 People: Marie-Curie Actions/ ; }, abstract = {Protists have fundamental ecological roles in marine environments and their diversity is being increasingly explored, yet little is known about the quantitative importance of specific taxa in these ecosystems. Here we optimized a newly developed automated system of image acquisition and image analysis to enumerate minute uncultured cells of different sizes targeted by fluorescence in situ hybridization. The automated counting routine was highly reproducible, well correlated with manual counts, and was then applied on surface and deep chlorophyll maximum samples from the Malaspina 2010 circumnavigation. The three targeted uncultured taxa (MAST-4, MAST-7 and MAST-1C) were found in virtually all samples from several ocean basins (Atlantic, Indian and Pacific) in fairly constant cell abundances, following typical lognormal distributions. Their global abundances averaged 49, 23 and 7 cells ml-1 , respectively, and altogether the three groups accounted for about 10%-20% of heterotrophic picoeukaryotes. Our innovative high-throughput cell counting routine allows for the first time a direct assessment of the biogeographic distribution of small protists (< 5 μm) and shows the ubiquity in sunlit oceans of three bacterivorous taxa, suggesting their key roles in marine ecosystems.}, } @article {pmid30209865, year = {2018}, author = {Zhang, X and Johnston, ER and Barberán, A and Ren, Y and Wang, Z and Han, X}, title = {Effect of intermediate disturbance on soil microbial functional diversity depends on the amount of effective resources.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3862-3875}, doi = {10.1111/1462-2920.14407}, pmid = {30209865}, issn = {1462-2920}, support = {BSRF201714//Central Public-interest Scientific Institution Basal Research Fund/ ; 2016YFC0500702//National Key Research and Development Program/ ; XDB15010404//Strategic Priority Research Program of CAS/ ; }, abstract = {Many anthropogenic environmental changes are leading to a rapid decline in soil microbial functional diversity. However, ecological mechanisms that can serve to counteract/resist the diversity loss remain largely underexplored. In particular, although intermediate disturbance and increased amount of effective resources can promote the diversity of higher organisms, the potential role of these factors, and their combination, in maintaining microbial functional diversity is poorly studied. We conducted a 5-year experiment in a Eurasian steppe, manipulating mowing, nitrogen addition, phosphorus addition and their combinations. Nitrogen addition decreased soil pH by ~0.6 and bacterial abundance by ~19.5%, causing a disturbance effect. Phosphorus addition significantly decreased the effective amount of soil carbon-, nitrogen-, phosphorus- and water-relevant resources. Across all nitrogen-addition treatments subject to intermediate disturbance, there was a significant positive correlation between soil effective resource amount and microbial gene richness (r > 0.6, p < 0.01), which was elevated, in part, due to the increased fungal abundance. In contrast, significant correlations between gene richness and resource amount were not found under low-disturbance conditions. Overall, gene richness was greatest under conditions of both intermediate disturbance and ample effective resources, suggesting that the two factors could be manipulated in combination for the maintenance of microbial functional diversity.}, } @article {pmid30209690, year = {2018}, author = {Schwartz, AW}, title = {Correction to: Publication of Abstracts and Full Papers from the International Conference on the Origin of Life, San Diego, 2017.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {}, number = {}, pages = {}, doi = {10.1007/s11084-018-9563-8}, pmid = {30209690}, issn = {1573-0875}, abstract = {Plans for the publication of Abstracts from the meeting have been cancelled. However, manuscripts for full papers will still be considered for publication in OLEB.}, } @article {pmid30209570, year = {2018}, author = {Moreira, EA and Alvarez, TM and Persinoti, GF and Paixão, DAA and Menezes, LR and Cairo, JPF and Squina, FM and Costa-Leonardo, AM and Carrijo, T and Arab, A}, title = {Microbial Communities of the Gut and Nest of the Humus- and Litter-Feeding Termite Procornitermes araujoi (Syntermitinae).}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {30209570}, issn = {1432-0991}, support = {2015/21497-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, abstract = {The evolution of the symbiotic association with microbes allowed termites to decompose ingested lignocellulose from plant-derived substrates, including herbivore dung and soil humus. Representatives of the Syntermitinae (Termitidae) range in their feeding habits from wood and litter-feeding to humus-feeding species. However, only limited information is available about their feeding ecology and associated microbial communities. Here we conducted a study of the microbial communities associated to the termite Procornitermes araujoi using Illumina sequencing of the 16S and ITS rRNA genes. This species has been previously included in different feeding guilds. However, most aspects of its feeding ecology are unknown, especially those associated to its symbiotic microbiota. Our results showed that the microbial communities of termite guts and nest substrates of P. araujoi differed significantly for bacteria and fungi. Firmicutes dominated the bacterial gut community of both workers and soldiers, whereas Actinobacteria was found in higher prevalence in the nest walls. Sordariomycetes was the most abundant fungal class in both gut and nest samples and distinguish P. araujoi from the grass/litter feeding Cornitermes cumulans. Our results also showed that diversity of gut bacteria were higher in P. araujoi and Silvestritermes euamignathus than in the grass/litter feeders (C. cumulans and Syntermes dirus), that could indicate an adaptation of the microbial community of polyphagous termites to the higher complexity of their diets.}, } @article {pmid30209401, year = {2018}, author = {Whyte, WA and Bilodeau, S and Orlando, DA and Hoke, HA and Frampton, GM and Foster, CT and Cowley, SM and Young, RA}, title = {Author Correction: Enhancer decommissioning by LSD1 during embryonic stem cell differentiation.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {E24}, doi = {10.1038/s41586-018-0487-2}, pmid = {30209401}, issn = {1476-4687}, abstract = {In this Letter, the western blot for LSD1 in the right panel of Fig. 2b ('TCP +') was inadvertently duplicated from the tubulin blot immediately below. The actual tubulin western blot shows the same result, with no significant change to the levels of tubulin (see Fig. 1 of this Amendment). In addition, the western blots for LSD1 and HDAC1 of Fig. 3b and c have been corrected to include vertical black lines to delineate the juxtaposition of lanes that were non-adjacent in the original blotting experiment (see Fig. 2 of this Amendment). Supplementary Figs. 4a, 6b and 9b have also been corrected to delineate non-adjacent lanes with vertical black lines (see Supplementary Information of this Amendment). The complete raw data images from these western blotting experiments can also be found in the Supplementary Information of this Amendment. The original Letter has not been corrected.}, } @article {pmid30209400, year = {2018}, author = {Liang, YL and Khoshouei, M and Deganutti, G and Glukhova, A and Koole, C and Peat, TS and Radjainia, M and Plitzko, JM and Baumeister, W and Miller, LJ and Hay, DL and Christopoulos, A and Reynolds, CA and Wootten, D and Sexton, PM}, title = {Cryo-EM structure of the active, Gs-protein complexed, human CGRP receptor.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {492-497}, pmid = {30209400}, issn = {1476-4687}, abstract = {Calcitonin gene-related peptide (CGRP) is a widely expressed neuropeptide that has a major role in sensory neurotransmission. The CGRP receptor is a heterodimer of the calcitonin receptor-like receptor (CLR) class B G-protein-coupled receptor and a type 1 transmembrane domain protein, receptor activity-modifying protein 1 (RAMP1). Here we report the structure of the human CGRP receptor in complex with CGRP and the Gs-protein heterotrimer at 3.3 Å global resolution, determined by Volta phase-plate cryo-electron microscopy. The receptor activity-modifying protein transmembrane domain sits at the interface between transmembrane domains 3, 4 and 5 of CLR, and stabilizes CLR extracellular loop 2. RAMP1 makes only limited direct contact with CGRP, consistent with its function in allosteric modulation of CLR. Molecular dynamics simulations indicate that RAMP1 provides stability to the receptor complex, particularly in the positioning of the extracellular domain of CLR. This work provides insights into the control of G-protein-coupled receptor function.}, } @article {pmid30209399, year = {2018}, author = {Findlay, GM and Daza, RM and Martin, B and Zhang, MD and Leith, AP and Gasperini, M and Janizek, JD and Huang, X and Starita, LM and Shendure, J}, title = {Accurate classification of BRCA1 variants with saturation genome editing.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {217-222}, pmid = {30209399}, issn = {1476-4687}, support = {DP1 HG007811/HG/NHGRI NIH HHS/United States ; F30 CA213728/CA/NCI NIH HHS/United States ; R01 HG009136/HG/NHGRI NIH HHS/United States ; }, abstract = {Variants of uncertain significance fundamentally limit the clinical utility of genetic information. The challenge they pose is epitomized by BRCA1, a tumour suppressor gene in which germline loss-of-function variants predispose women to breast and ovarian cancer. Although BRCA1 has been sequenced in millions of women, the risk associated with most newly observed variants cannot be definitively assigned. Here we use saturation genome editing to assay 96.5% of all possible single-nucleotide variants (SNVs) in 13 exons that encode functionally critical domains of BRCA1. Functional effects for nearly 4,000 SNVs are bimodally distributed and almost perfectly concordant with established assessments of pathogenicity. Over 400 non-functional missense SNVs are identified, as well as around 300 SNVs that disrupt expression. We predict that these results will be immediately useful for the clinical interpretation of BRCA1 variants, and that this approach can be extended to overcome the challenge of variants of uncertain significance in additional clinically actionable genes.}, } @article {pmid30209398, year = {2018}, author = {Yin, JX and Zhang, SS and Li, H and Jiang, K and Chang, G and Zhang, B and Lian, B and Xiang, C and Belopolski, I and Zheng, H and Cochran, TA and Xu, SY and Bian, G and Liu, K and Chang, TR and Lin, H and Lu, ZY and Wang, Z and Jia, S and Wang, W and Hasan, MZ}, title = {Giant and anisotropic many-body spin-orbit tunability in a strongly correlated kagome magnet.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {91-95}, doi = {10.1038/s41586-018-0502-7}, pmid = {30209398}, issn = {1476-4687}, abstract = {Owing to the unusual geometry of kagome lattices-lattices made of corner-sharing triangles-their electrons are useful for studying the physics of frustrated, correlated and topological quantum electronic states1-9. In the presence of strong spin-orbit coupling, the magnetic and electronic structures of kagome lattices are further entangled, which can lead to hitherto unknown spin-orbit phenomena. Here we use a combination of vector-magnetic-field capability and scanning tunnelling microscopy to elucidate the spin-orbit nature of the kagome ferromagnet Fe3Sn2 and explore the associated exotic correlated phenomena. We discover that a many-body electronic state from the kagome lattice couples strongly to the vector field with three-dimensional anisotropy, exhibiting a magnetization-driven giant nematic (two-fold-symmetric) energy shift. Probing the fermionic quasi-particle interference reveals consistent spontaneous nematicity-a clear indication of electron correlation-and vector magnetization is capable of altering this state, thus controlling the many-body electronic symmetry. These spin-driven giant electronic responses go well beyond Zeeman physics and point to the realization of an underlying correlated magnetic topological phase. The tunability of this kagome magnet reveals a strong interplay between an externally applied field, electronic excitations and nematicity, providing new ways of controlling spin-orbit properties and exploring emergent phenomena in topological or quantum materials10-12.}, } @article {pmid30209397, year = {2018}, author = {Seehawer, M and Heinzmann, F and D'Artista, L and Harbig, J and Roux, PF and Hoenicke, L and Dang, H and Klotz, S and Robinson, L and Doré, G and Rozenblum, N and Kang, TW and Chawla, R and Buch, T and Vucur, M and Roth, M and Zuber, J and Luedde, T and Sipos, B and Longerich, T and Heikenwälder, M and Wang, XW and Bischof, O and Zender, L}, title = {Necroptosis microenvironment directs lineage commitment in liver cancer.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {69-75}, doi = {10.1038/s41586-018-0519-y}, pmid = {30209397}, issn = {1476-4687}, support = {R01 CA136533/CA/NCI NIH HHS/United States ; }, abstract = {Primary liver cancer represents a major health problem. It comprises hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC), which differ markedly with regards to their morphology, metastatic potential and responses to therapy. However, the regulatory molecules and tissue context that commit transformed hepatic cells towards HCC or ICC are largely unknown. Here we show that the hepatic microenvironment epigenetically shapes lineage commitment in mosaic mouse models of liver tumorigenesis. Whereas a necroptosis-associated hepatic cytokine microenvironment determines ICC outgrowth from oncogenically transformed hepatocytes, hepatocytes containing identical oncogenic drivers give rise to HCC if they are surrounded by apoptotic hepatocytes. Epigenome and transcriptome profiling of mouse HCC and ICC singled out Tbx3 and Prdm5 as major microenvironment-dependent and epigenetically regulated lineage-commitment factors, a function that is conserved in humans. Together, our results provide insight into lineage commitment in liver tumorigenesis, and explain molecularly why common liver-damaging risk factors can lead to either HCC or ICC.}, } @article {pmid30209396, year = {2018}, author = {Schneider, DM and Sundararajan, J and Mooney, R}, title = {A cortical filter that learns to suppress the acoustic consequences of movement.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {391-395}, pmid = {30209396}, issn = {1476-4687}, support = {R01 DC013826/DC/NIDCD NIH HHS/United States ; }, abstract = {Sounds can arise from the environment and also predictably from many of our own movements, such as vocalizing, walking, or playing music. The capacity to anticipate these movement-related (reafferent) sounds and distinguish them from environmental sounds is essential for normal hearing1,2, but the neural circuits that learn to anticipate the often arbitrary and changeable sounds that result from our movements remain largely unknown. Here we developed an acoustic virtual reality (aVR) system in which a mouse learned to associate a novel sound with its locomotor movements, allowing us to identify the neural circuit mechanisms that learn to suppress reafferent sounds and to probe the behavioural consequences of this predictable sensorimotor experience. We found that aVR experience gradually and selectively suppressed auditory cortical responses to the reafferent frequency, in part by strengthening motor cortical activation of auditory cortical inhibitory neurons that respond to the reafferent tone. This plasticity is behaviourally adaptive, as aVR-experienced mice showed an enhanced ability to detect non-reafferent tones during movement. Together, these findings describe a dynamic sensory filter that involves motor cortical inputs to the auditory cortex that can be shaped by experience to selectively suppress the predictable acoustic consequences of movement.}, } @article {pmid30209395, year = {2018}, author = {Liu, Y and Latremoliere, A and Li, X and Zhang, Z and Chen, M and Wang, X and Fang, C and Zhu, J and Alexandre, C and Gao, Z and Chen, B and Ding, X and Zhou, JY and Zhang, Y and Chen, C and Wang, KH and Woolf, CJ and He, Z}, title = {Touch and tactile neuropathic pain sensitivity are set by corticospinal projections.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {547-550}, pmid = {30209395}, issn = {1476-4687}, support = {R01 NS096294/NS/NINDS NIH HHS/United States ; R35 NS105076/NS/NINDS NIH HHS/United States ; P30 HD018655/HD/NICHD NIH HHS/United States ; P30 EY012196/EY/NEI NIH HHS/United States ; ZIA MH002897/MH/NIMH NIH HHS/United States ; }, abstract = {Current models of somatosensory perception emphasize transmission from primary sensory neurons to the spinal cord and on to the brain1-4. Mental influence on perception is largely assumed to occur locally within the brain. Here we investigate whether sensory inflow through the spinal cord undergoes direct top-down control by the cortex. Although the corticospinal tract (CST) is traditionally viewed as a primary motor pathway5, a subset of corticospinal neurons (CSNs) originating in the primary and secondary somatosensory cortex directly innervate the spinal dorsal horn via CST axons. Either reduction in somatosensory CSN activity or transection of the CST in mice selectively impairs behavioural responses to light touch without altering responses to noxious stimuli. Moreover, such CSN manipulation greatly attenuates tactile allodynia in a model of peripheral neuropathic pain. Tactile stimulation activates somatosensory CSNs, and their corticospinal projections facilitate light-touch-evoked activity of cholecystokinin interneurons in the deep dorsal horn. This touch-driven feed-forward spinal-cortical-spinal sensitization loop is important for the recruitment of spinal nociceptive neurons under tactile allodynia. These results reveal direct cortical modulation of normal and pathological tactile sensory processing in the spinal cord and open up opportunities for new treatments for neuropathic pain.}, } @article {pmid30209394, year = {2018}, author = {Henshilwood, CS and d'Errico, F and van Niekerk, KL and Dayet, L and Queffelec, A and Pollarolo, L}, title = {An abstract drawing from the 73,000-year-old levels at Blombos Cave, South Africa.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {115-118}, doi = {10.1038/s41586-018-0514-3}, pmid = {30209394}, issn = {1476-4687}, abstract = {Depictive and abstract representations produced by drawing-known from Europe, Africa and Southeast Asia after 40,000 years ago-are a prime indicator of modern cognition and behaviour1. Here we report a cross-hatched pattern drawn with an ochre crayon on a ground silcrete flake recovered from approximately 73,000-year-old Middle Stone Age levels at Blombos Cave, South Africa. Our microscopic and chemical analyses of the pattern confirm that red ochre pigment was intentionally applied to the flake with an ochre crayon. The object comes from a level associated with stone tools of the Still Bay techno-complex that has previously yielded shell beads, cross-hatched engravings on ochre pieces and a variety of innovative technologies2-5. This notable discovery pre-dates the earliest previously known abstract and figurative drawings by at least 30,000 years. This drawing demonstrates the ability of early Homo sapiens in southern Africa to produce graphic designs on various media using different techniques.}, } @article {pmid30209393, year = {2018}, author = {Dou, J and Vorobieva, AA and Sheffler, W and Doyle, LA and Park, H and Bick, MJ and Mao, B and Foight, GW and Lee, MY and Gagnon, LA and Carter, L and Sankaran, B and Ovchinnikov, S and Marcos, E and Huang, PS and Vaughan, JC and Stoddard, BL and Baker, D}, title = {De novo design of a fluorescence-activating β-barrel.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {485-491}, pmid = {30209393}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM115545/GM/NIGMS NIH HHS/United States ; DE-AC02-05CH11231//Department of Energy/International ; }, abstract = {The regular arrangements of β-strands around a central axis in β-barrels and of α-helices in coiled coils contrast with the irregular tertiary structures of most globular proteins, and have fascinated structural biologists since they were first discovered. Simple parametric models have been used to design a wide range of α-helical coiled-coil structures, but to date there has been no success with β-barrels. Here we show that accurate de novo design of β-barrels requires considerable symmetry-breaking to achieve continuous hydrogen-bond connectivity and eliminate backbone strain. We then build ensembles of β-barrel backbone models with cavity shapes that match the fluorogenic compound DFHBI, and use a hierarchical grid-based search method to simultaneously optimize the rigid-body placement of DFHBI in these cavities and the identities of the surrounding amino acids to achieve high shape and chemical complementarity. The designs have high structural accuracy and bind and fluorescently activate DFHBI in vitro and in Escherichia coli, yeast and mammalian cells. This de novo design of small-molecule binding activity, using backbones custom-built to bind the ligand, should enable the design of increasingly sophisticated ligand-binding proteins, sensors and catalysts that are not limited by the backbone geometries available in known protein structures.}, } @article {pmid30209392, year = {2018}, author = {Alexander, TB and Gu, Z and Iacobucci, I and Dickerson, K and Choi, JK and Xu, B and Payne-Turner, D and Yoshihara, H and Loh, ML and Horan, J and Buldini, B and Basso, G and Elitzur, S and de Haas, V and Zwaan, CM and Yeoh, A and Reinhardt, D and Tomizawa, D and Kiyokawa, N and Lammens, T and De Moerloose, B and Catchpoole, D and Hori, H and Moorman, A and Moore, AS and Hrusak, O and Meshinchi, S and Orgel, E and Devidas, M and Borowitz, M and Wood, B and Heerema, NA and Carrol, A and Yang, YL and Smith, MA and Davidsen, TM and Hermida, LC and Gesuwan, P and Marra, MA and Ma, Y and Mungall, AJ and Moore, RA and Jones, SJM and Valentine, M and Janke, LJ and Rubnitz, JE and Pui, CH and Ding, L and Liu, Y and Zhang, J and Nichols, KE and Downing, JR and Cao, X and Shi, L and Pounds, S and Newman, S and Pei, D and Guidry Auvil, JM and Gerhard, DS and Hunger, SP and Inaba, H and Mullighan, CG}, title = {The genetic basis and cell of origin of mixed phenotype acute leukaemia.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {373-379}, pmid = {30209392}, issn = {1476-4687}, support = {R35 CA197695/CA/NCI NIH HHS/United States ; U10 CA098413/CA/NCI NIH HHS/United States ; U24 CA114766/CA/NCI NIH HHS/United States ; P30 CA021765/CA/NCI NIH HHS/United States ; U10 CA180899/CA/NCI NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, abstract = {Mixed phenotype acute leukaemia (MPAL) is a high-risk subtype of leukaemia with myeloid and lymphoid features, limited genetic characterization, and a lack of consensus regarding appropriate therapy. Here we show that the two principal subtypes of MPAL, T/myeloid (T/M) and B/myeloid (B/M), are genetically distinct. Rearrangement of ZNF384 is common in B/M MPAL, and biallelic WT1 alterations are common in T/M MPAL, which shares genomic features with early T-cell precursor acute lymphoblastic leukaemia. We show that the intratumoral immunophenotypic heterogeneity characteristic of MPAL is independent of somatic genetic variation, that founding lesions arise in primitive haematopoietic progenitors, and that individual phenotypic subpopulations can reconstitute the immunophenotypic diversity in vivo. These findings indicate that the cell of origin and founding lesions, rather than an accumulation of distinct genomic alterations, prime tumour cells for lineage promiscuity. Moreover, these findings position MPAL in the spectrum of immature leukaemias and provide a genetically informed framework for future clinical trials of potential treatments for MPAL.}, } @article {pmid30209391, year = {2018}, author = {Light, SH and Su, L and Rivera-Lugo, R and Cornejo, JA and Louie, A and Iavarone, AT and Ajo-Franklin, CM and Portnoy, DA}, title = {A flavin-based extracellular electron transfer mechanism in diverse Gram-positive bacteria.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {140-144}, pmid = {30209391}, issn = {1476-4687}, support = {F32 AI136389/AI/NIAID NIH HHS/United States ; P01 AI063302/AI/NIAID NIH HHS/United States ; R01 AI027655/AI/NIAID NIH HHS/United States ; }, abstract = {Extracellular electron transfer (EET) describes microbial bioelectrochemical processes in which electrons are transferred from the cytosol to the exterior of the cell1. Mineral-respiring bacteria use elaborate haem-based electron transfer mechanisms2-4 but the existence and mechanistic basis of other EETs remain largely unknown. Here we show that the food-borne pathogen Listeria monocytogenes uses a distinctive flavin-based EET mechanism to deliver electrons to iron or an electrode. By performing a forward genetic screen to identify L. monocytogenes mutants with diminished extracellular ferric iron reductase activity, we identified an eight-gene locus that is responsible for EET. This locus encodes a specialized NADH dehydrogenase that segregates EET from aerobic respiration by channelling electrons to a discrete membrane-localized quinone pool. Other proteins facilitate the assembly of an abundant extracellular flavoprotein that, in conjunction with free-molecule flavin shuttles, mediates electron transfer to extracellular acceptors. This system thus establishes a simple electron conduit that is compatible with the single-membrane structure of the Gram-positive cell. Activation of EET supports growth on non-fermentable carbon sources, and an EET mutant exhibited a competitive defect within the mouse gastrointestinal tract. Orthologues of the genes responsible for EET are present in hundreds of species across the Firmicutes phylum, including multiple pathogens and commensal members of the intestinal microbiota, and correlate with EET activity in assayed strains. These findings suggest a greater prevalence of EET-based growth capabilities and establish a previously underappreciated relevance for electrogenic bacteria across diverse environments, including host-associated microbial communities and infectious disease.}, } @article {pmid30209390, year = {2018}, author = {Akcakaya, P and Bobbin, ML and Guo, JA and Malagon-Lopez, J and Clement, K and Garcia, SP and Fellows, MD and Porritt, MJ and Firth, MA and Carreras, A and Baccega, T and Seeliger, F and Bjursell, M and Tsai, SQ and Nguyen, NT and Nitsch, R and Mayr, LM and Pinello, L and Bohlooly-Y, M and Aryee, MJ and Maresca, M and Joung, JK}, title = {In vivo CRISPR editing with no detectable genome-wide off-target mutations.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {416-419}, pmid = {30209390}, issn = {1476-4687}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; R00 HG008399/HG/NHGRI NIH HHS/United States ; R35 GM118158/GM/NIGMS NIH HHS/United States ; }, abstract = {CRISPR-Cas genome-editing nucleases hold substantial promise for developing human therapeutic applications1-6 but identifying unwanted off-target mutations is important for clinical translation7. A well-validated method that can reliably identify off-targets in vivo has not been described to date, which means it is currently unclear whether and how frequently these mutations occur. Here we describe 'verification of in vivo off-targets' (VIVO), a highly sensitive strategy that can robustly identify the genome-wide off-target effects of CRISPR-Cas nucleases in vivo. We use VIVO and a guide RNA deliberately designed to be promiscuous to show that CRISPR-Cas nucleases can induce substantial off-target mutations in mouse livers in vivo. More importantly, we also use VIVO to show that appropriately designed guide RNAs can direct efficient in vivo editing in mouse livers with no detectable off-target mutations. VIVO provides a general strategy for defining and quantifying the off-target effects of gene-editing nucleases in whole organisms, thereby providing a blueprint to foster the development of therapeutic strategies that use in vivo gene editing.}, } @article {pmid30209386, year = {2018}, author = {}, title = {Election security, CRISPR patents and Australia's drought.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {154-155}, doi = {10.1038/d41586-018-06609-5}, pmid = {30209386}, issn = {1476-4687}, mesh = {Animals ; Australia ; Clustered Regularly Interspaced Short Palindromic Repeats ; *Droughts ; *Fur Seals ; Humans ; Politics ; }, } @article {pmid30209385, year = {2018}, author = {}, title = {The earliest known drawing in history sends a message through 73,000 years.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {149}, doi = {10.1038/d41586-018-06657-x}, pmid = {30209385}, issn = {1476-4687}, mesh = {*Archaeology ; Carbonates ; Caves ; *Neanderthals ; }, } @article {pmid30209384, year = {2018}, author = {Ioannidis, JPA and Klavans, R and Boyack, KW}, title = {Thousands of scientists publish a paper every five days.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {167-169}, doi = {10.1038/d41586-018-06185-8}, pmid = {30209384}, issn = {1476-4687}, } @article {pmid30209383, year = {2018}, author = {Jones, N}, title = {How to stop data centres from gobbling up the world's electricity.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {163-166}, doi = {10.1038/d41586-018-06610-y}, pmid = {30209383}, issn = {1476-4687}, } @article {pmid30209382, year = {2018}, author = {}, title = {Celebrate the mathematics of Emmy Noether.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {149-150}, doi = {10.1038/d41586-018-06658-w}, pmid = {30209382}, issn = {1476-4687}, } @article {pmid30209381, year = {2018}, author = {Kent, KJ}, title = {How Earth-observation scientists are weathering budget cuts and political scepticism.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {S5-S7}, doi = {10.1038/d41586-018-06615-7}, pmid = {30209381}, issn = {1476-4687}, } @article {pmid30209380, year = {2018}, author = {Sutton, R}, title = {Attributing extreme weather to climate change is not a done deal.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {177}, doi = {10.1038/d41586-018-06631-7}, pmid = {30209380}, issn = {1476-4687}, } @article {pmid30209379, year = {2018}, author = {David, AA}, title = {Pedagogy helps to prepare undergraduates for the research lab.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {177}, doi = {10.1038/d41586-018-06630-8}, pmid = {30209379}, issn = {1476-4687}, } @article {pmid30209378, year = {2018}, author = {Black, A and Waipara, N and Gerth, M}, title = {Calling time on New Zealand's oldest tree species.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {177}, doi = {10.1038/d41586-018-06629-1}, pmid = {30209378}, issn = {1476-4687}, } @article {pmid30209377, year = {2018}, author = {Rezende, SM}, title = {Spins travel far in an antiferromagnet.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {181-182}, doi = {10.1038/d41586-018-06197-4}, pmid = {30209377}, issn = {1476-4687}, mesh = {*Ferric Compounds ; Physical Phenomena ; Spin Labels ; *Travel ; }, } @article {pmid30209376, year = {2018}, author = {Walker, TR}, title = {Help graduate students to become good peer reviewers.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {177}, doi = {10.1038/d41586-018-06632-6}, pmid = {30209376}, issn = {1476-4687}, mesh = {*Peer Group ; Peer Review ; Peer Review, Research ; Publishing ; *Students ; }, } @article {pmid30209375, year = {2018}, author = {Woodruff, JD}, title = {Future of tidal wetlands depends on coastal management.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {183-185}, doi = {10.1038/d41586-018-06190-x}, pmid = {30209375}, issn = {1476-4687}, mesh = {Climate Change ; Conservation of Natural Resources ; *Tidal Waves ; *Wetlands ; }, } @article {pmid30209374, year = {2018}, author = {Veuthey, TL and Thompson, S}, title = {Why you need an agenda for meetings with your principal investigator.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {277}, doi = {10.1038/d41586-018-06619-3}, pmid = {30209374}, issn = {1476-4687}, } @article {pmid30209373, year = {2018}, author = {Haslam, SA}, title = {The self-made women who created the Myers-Briggs.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {176}, doi = {10.1038/d41586-018-06614-8}, pmid = {30209373}, issn = {1476-4687}, } @article {pmid30209371, year = {2018}, author = {Gantenbein, S and Masania, K and Woigk, W and Sesseg, JPW and Tervoort, TA and Studart, AR}, title = {Three-dimensional printing of hierarchical liquid-crystal-polymer structures.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {226-230}, doi = {10.1038/s41586-018-0474-7}, pmid = {30209371}, issn = {1476-4687}, abstract = {Fibre-reinforced polymer structures are often used when stiff lightweight materials are required, such as in aircraft, vehicles and biomedical implants. Despite their very high stiffness and strength1, such lightweight materials require energy- and labour-intensive fabrication processes2, exhibit typically brittle fracture and are difficult to shape and recycle3,4. This is in stark contrast to lightweight biological materials such as bone, silk and wood, which form by directed self-assembly into complex, hierarchically structured shapes with outstanding mechanical properties5-11, and are circularly integrated into the environment. Here we demonstrate a three-dimensional (3D) printing approach to generate recyclable lightweight structures with hierarchical architectures, complex geometries and unprecedented stiffness and toughness. Their features arise from the self-assembly of liquid-crystal polymer molecules into highly oriented domains during extrusion of the molten feedstock material. By orienting the molecular domains with the print path, we are able to reinforce the polymer structure according to the expected mechanical stresses, leading to stiffness, strength and toughness that outperform state-of-the-art 3D-printed polymers by an order of magnitude and are comparable with the highest-performance lightweight composites1,12. The ability to combine the top-down shaping freedom of 3D printing with bottom-up molecular control over polymer orientation opens up the possibility to freely design and realize structures without the typical restrictions of current manufacturing processes.}, } @article {pmid30209370, year = {2018}, author = {Lebrun, R and Ross, A and Bender, SA and Qaiumzadeh, A and Baldrati, L and Cramer, J and Brataas, A and Duine, RA and Kläui, M}, title = {Tunable long-distance spin transport in a crystalline antiferromagnetic iron oxide.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {222-225}, doi = {10.1038/s41586-018-0490-7}, pmid = {30209370}, issn = {1476-4687}, abstract = {Spintronics relies on the transport of spins, the intrinsic angular momentum of electrons, as an alternative to the transport of electron charge as in conventional electronics. The long-term goal of spintronics research is to develop spin-based, low-dissipation computing-technology devices. Recently, long-distance transport of a spin current was demonstrated across ferromagnetic insulators1. However, antiferromagnetically ordered materials, the most common class of magnetic materials, have several crucial advantages over ferromagnetic systems for spintronics applications2: antiferromagnets have no net magnetic moment, making them stable and impervious to external fields, and can be operated at terahertz-scale frequencies3. Although the properties of antiferromagnets are desirable for spin transport4-7, indirect observations of such transport indicate that spin transmission through antiferromagnets is limited to only a few nanometres8-10. Here we demonstrate long-distance propagation of spin currents through a single crystal of the antiferromagnetic insulator haematite (α-Fe2O3)11, the most common antiferromagnetic iron oxide, by exploiting the spin Hall effect for spin injection. We control the flow of spin current across a haematite-platinum interface-at which spins accumulate, generating the spin current-by tuning the antiferromagnetic resonance frequency using an external magnetic field12. We find that this simple antiferromagnetic insulator conveys spin information parallel to the antiferromagnetic Néel order over distances of more than tens of micrometres. This mechanism transports spins as efficiently as the most promising complex ferromagnets1. Our results pave the way to electrically tunable, ultrafast, low-power, antiferromagnetic-insulator-based spin-logic devices6,13 that operate without magnetic fields at room temperature.}, } @article {pmid30209369, year = {2018}, author = {Turner, DL and Wilson, LB and Liu, TZ and Cohen, IJ and Schwartz, SJ and Osmane, A and Fennell, JF and Clemmons, JH and Blake, JB and Westlake, J and Mauk, BH and Jaynes, AN and Leonard, T and Baker, DN and Strangeway, RJ and Russell, CT and Gershman, DJ and Avanov, L and Giles, BL and Torbert, RB and Broll, J and Gomez, RG and Fuselier, SA and Burch, JL}, title = {Autogenous and efficient acceleration of energetic ions upstream of Earth's bow shock.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {206-210}, doi = {10.1038/s41586-018-0472-9}, pmid = {30209369}, issn = {1476-4687}, support = {N-999999//Intramural NASA/United States ; NNG04EB99C/NASA/NASA/United States ; NNX12AQ50G/NASA/NASA/United States ; }, abstract = {Earth and its magnetosphere are immersed in the supersonic flow of the solar-wind plasma that fills interplanetary space. As the solar wind slows and deflects to flow around Earth, or any other obstacle, a 'bow shock' forms within the flow. Under almost all solar-wind conditions, planetary bow shocks such as Earth's are collisionless, supercritical shocks, meaning that they reflect and accelerate a fraction of the incident solar-wind ions as an energy dissipation mechanism1,2, which results in the formation of a region called the ion foreshock3. In the foreshock, large-scale, transient phenomena can develop, such as 'hot flow anomalies'4-9, which are concentrations of shock-reflected, suprathermal ions that are channelled and accumulated along certain structures in the upstream magnetic field. Hot flow anomalies evolve explosively, often resulting in the formation of new shocks along their upstream edges5,10, and potentially contribute to particle acceleration11-13, but there have hitherto been no observations to constrain this acceleration or to confirm the underlying mechanism. Here we report observations of a hot flow anomaly accelerating solar-wind ions from roughly 1-10 kiloelectronvolts up to almost 1,000 kiloelectronvolts. The acceleration mechanism depends on the mass and charge state of the ions and is consistent with first-order Fermi acceleration14,15. The acceleration that we observe results from only the interaction of Earth's bow shock with the solar wind, but produces a much, much larger number of energetic particles compared to what would typically be produced in the foreshock from acceleration at the bow shock. Such autogenous and efficient acceleration at quasi-parallel bow shocks (the normal direction of which are within about 45 degrees of the interplanetary magnetic field direction) provides a potential solution to Fermi's 'injection problem', which requires an as-yet-unexplained seed population of energetic particles, and implies that foreshock transients may be important in the generation of cosmic rays at astrophysical shocks throughout the cosmos.}, } @article {pmid30209368, year = {2018}, author = {Schuerch, M and Spencer, T and Temmerman, S and Kirwan, ML and Wolff, C and Lincke, D and McOwen, CJ and Pickering, MD and Reef, R and Vafeidis, AT and Hinkel, J and Nicholls, RJ and Brown, S}, title = {Future response of global coastal wetlands to sea-level rise.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {231-234}, doi = {10.1038/s41586-018-0476-5}, pmid = {30209368}, issn = {1476-4687}, support = {1426981//National Science Foundation/International ; 1654374//National Science Foundation/International ; }, abstract = {The response of coastal wetlands to sea-level rise during the twenty-first century remains uncertain. Global-scale projections suggest that between 20 and 90 per cent (for low and high sea-level rise scenarios, respectively) of the present-day coastal wetland area will be lost, which will in turn result in the loss of biodiversity and highly valued ecosystem services1-3. These projections do not necessarily take into account all essential geomorphological4-7 and socio-economic system feedbacks8. Here we present an integrated global modelling approach that considers both the ability of coastal wetlands to build up vertically by sediment accretion, and the accommodation space, namely, the vertical and lateral space available for fine sediments to accumulate and be colonized by wetland vegetation. We use this approach to assess global-scale changes in coastal wetland area in response to global sea-level rise and anthropogenic coastal occupation during the twenty-first century. On the basis of our simulations, we find that, globally, rather than losses, wetland gains of up to 60 per cent of the current area are possible, if more than 37 per cent (our upper estimate for current accommodation space) of coastal wetlands have sufficient accommodation space, and sediment supply remains at present levels. In contrast to previous studies1-3, we project that until 2100, the loss of global coastal wetland area will range between 0 and 30 per cent, assuming no further accommodation space in addition to current levels. Our simulations suggest that the resilience of global wetlands is primarily driven by the availability of accommodation space, which is strongly influenced by the building of anthropogenic infrastructure in the coastal zone and such infrastructure is expected to change over the twenty-first century. Rather than being an inevitable consequence of global sea-level rise, our findings indicate that large-scale loss of coastal wetlands might be avoidable, if sufficient additional accommodation space can be created through careful nature-based adaptation solutions to coastal management.}, } @article {pmid30209367, year = {2018}, author = {Smith, PA and Koehler, MFT and Girgis, HS and Yan, D and Chen, Y and Chen, Y and Crawford, JJ and Durk, MR and Higuchi, RI and Kang, J and Murray, J and Paraselli, P and Park, S and Phung, W and Quinn, JG and Roberts, TC and Rougé, L and Schwarz, JB and Skippington, E and Wai, J and Xu, M and Yu, Z and Zhang, H and Tan, MW and Heise, CE}, title = {Optimized arylomycins are a new class of Gram-negative antibiotics.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {189-194}, doi = {10.1038/s41586-018-0483-6}, pmid = {30209367}, issn = {1476-4687}, abstract = {Multidrug-resistant bacteria are spreading at alarming rates, and despite extensive efforts no new class of antibiotic with activity against Gram-negative bacteria has been approved in over fifty years. Natural products and their derivatives have a key role in combating Gram-negative pathogens. Here we report chemical optimization of the arylomycins-a class of natural products with weak activity and limited spectrum-to obtain G0775, a molecule with potent, broad-spectrum activity against Gram-negative bacteria. G0775 inhibits the essential bacterial type I signal peptidase, a new antibiotic target, through an unprecedented molecular mechanism. It circumvents existing antibiotic resistance mechanisms and retains activity against contemporary multidrug-resistant Gram-negative clinical isolates in vitro and in several in vivo infection models. These findings demonstrate that optimized arylomycin analogues such as G0775 could translate into new therapies to address the growing threat of multidrug-resistant Gram-negative infections.}, } @article {pmid30209366, year = {2018}, author = {Yang, JS and Hsu, JW and Park, SY and Li, J and Oldham, WM and Beznoussenko, GV and Mironov, AA and Loscalzo, J and Hsu, VW}, title = {GAPDH inhibits intracellular pathways during starvation for cellular energy homeostasis.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {263-267}, pmid = {30209366}, issn = {1476-4687}, support = {U01 HG007690/HG/NHGRI NIH HHS/United States ; K08 HL128802/HL/NHLBI NIH HHS/United States ; R01 HL061795/HL/NHLBI NIH HHS/United States ; P50 GM107618/GM/NIGMS NIH HHS/United States ; R01 GM115683/GM/NIGMS NIH HHS/United States ; R01 GM058615/GM/NIGMS NIH HHS/United States ; U54 HL119145/HL/NHLBI NIH HHS/United States ; R37 HL061795/HL/NHLBI NIH HHS/United States ; R37 GM058615/GM/NIGMS NIH HHS/United States ; }, abstract = {Starvation poses a fundamental challenge to cell survival. Whereas the role of autophagy in promoting energy homeostasis in this setting has been extensively characterized1, other mechanisms are less well understood. Here we reveal that glyceraldehyde 3-phosphate dehydrogenase (GAPDH) inhibits coat protein I (COPI) transport by targeting a GTPase-activating protein (GAP) towards ADP-ribosylation factor 1 (ARF1) to suppress COPI vesicle fission. GAPDH inhibits multiple other transport pathways, also by targeting ARF GAPs. Further characterization suggests that this broad inhibition is activated by the cell during starvation to reduce energy consumption. These findings reveal a remarkable level of coordination among the intracellular transport pathways that underlies a critical mechanism of cellular energy homeostasis.}, } @article {pmid30209365, year = {2018}, author = {Miller, LE and Montroni, L and Koun, E and Salemme, R and Hayward, V and Farnè, A}, title = {Sensing with tools extends somatosensory processing beyond the body.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {239-242}, doi = {10.1038/s41586-018-0460-0}, pmid = {30209365}, issn = {1476-4687}, abstract = {The ability to extend sensory information processing beyond the nervous system1 has been observed throughout the animal kingdom; for example, when rodents palpate objects using whiskers2 and spiders localize prey using webs3. We investigated whether the ability to sense objects with tools4-9 represents an analogous information processing scheme in humans. Here we provide evidence from behavioural psychophysics, structural mechanics and neuronal modelling, which shows that tools are treated by the nervous system as sensory extensions of the body rather than as simple distal links between the hand and the environment10,11. We first demonstrate that tool users can accurately sense where an object contacts a wooden rod, just as is possible on the skin. We next demonstrate that the impact location is encoded by the modal response of the tool upon impact, reflecting a pre-neuronal stage of mechanical information processing akin to sensing with whiskers2 and webs3. Lastly, we use a computational model of tactile afferents12 to demonstrate that impact location can be rapidly re-encoded into a temporally precise spiking code. This code predicts the behaviour of human participants, providing evidence that the information encoded in motifs shapes localization. Thus, we show that this sensory capability emerges from the functional coupling between the material, biomechanical and neural levels of information processing13,14.}, } @article {pmid30209364, year = {2018}, author = {Kroupa, P and Haghi, H and Javanmardi, B and Zonoozi, AH and Müller, O and Banik, I and Wu, X and Zhao, H and Dabringhausen, J}, title = {Does the galaxy NGC1052-DF2 falsify Milgromian dynamics?.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {E4-E5}, doi = {10.1038/s41586-018-0429-z}, pmid = {30209364}, issn = {1476-4687}, } @article {pmid30209350, year = {2018}, author = {Clyde, D}, title = {The girl with Neanderthal and Denisovan parents.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {668-669}, doi = {10.1038/s41576-018-0054-6}, pmid = {30209350}, issn = {1471-0064}, } @article {pmid30209221, year = {2018}, author = {Ding, Y and Colozza, G and Sosa, EA and Moriyama, Y and Rundle, S and Salwinski, L and De Robertis, EM}, title = {Bighead is a Wnt antagonist secreted by the Xenopus Spemann organizer that promotes Lrp6 endocytosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9135-E9144}, pmid = {30209221}, issn = {1091-6490}, support = {R01 GM123126/GM/NIGMS NIH HHS/United States ; T34 GM008563/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Angiopoietins/genetics/metabolism ; Animals ; Endocytosis/*physiology ; Endoderm/cytology/metabolism ; Gastrula/cytology/metabolism ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; Low Density Lipoprotein Receptor-Related Protein-6/genetics/*metabolism ; Protein Binding ; Wnt Proteins/genetics/*metabolism ; Wnt Signaling Pathway/*physiology ; Xenopus Proteins/genetics/metabolism ; Xenopus laevis ; }, abstract = {The Xenopus laevis embryo has been subjected to almost saturating screens for molecules specifically expressed in dorsal Spemann organizer tissue. In this study, we performed high-throughput RNA sequencing of ectodermal explants, called animal caps, which normally give rise to epidermis. We analyzed dissociated animal cap cells that, through sustained activation of MAPK, differentiate into neural tissue. We also microinjected mRNAs for Cerberus, Chordin, FGF8, BMP4, Wnt8, and Xnr2, which induce neural or other germ layer differentiations. The searchable database provided here represents a valuable resource for the early vertebrate cell differentiation. These analyses resulted in the identification of a gene present in frog and fish, which we call Bighead. Surprisingly, at gastrula, it was expressed in the Spemann organizer and endoderm, rather than in ectoderm as we expected. Despite the plethora of genes already mined from Spemann organizer tissue, Bighead encodes a secreted protein that proved to be a potent inhibitor of Wnt signaling in a number of embryological and cultured cell signaling assays. Overexpression of Bighead resulted in large head structures very similar to those of the well-known Wnt antagonists Dkk1 and Frzb-1. Knockdown of Bighead with specific antisense morpholinos resulted in embryos with reduced head structures, due to increased Wnt signaling. Bighead protein bound specifically to the Wnt coreceptor lipoprotein receptor-related protein 6 (Lrp6), leading to its removal from the cell surface. Bighead joins two other Wnt antagonists, Dkk1 and Angptl4, which function as Lrp6 endocytosis regulators. These results suggest that endocytosis plays a crucial role in Wnt signaling.}, } @article {pmid30209220, year = {2018}, author = {Eguchi, T and Kuwahara, T and Sakurai, M and Komori, T and Fujimoto, T and Ito, G and Yoshimura, SI and Harada, A and Fukuda, M and Koike, M and Iwatsubo, T}, title = {LRRK2 and its substrate Rab GTPases are sequentially targeted onto stressed lysosomes and maintain their homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9115-E9124}, pmid = {30209220}, issn = {1091-6490}, mesh = {3T3 Cells ; Animals ; Carrier Proteins/genetics/metabolism ; HEK293 Cells ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics/*metabolism ; Lysosomes/*enzymology/genetics ; Mice ; Mice, Knockout ; Phosphorylation ; RAW 264.7 Cells ; *Stress, Physiological ; rab GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {Leucine-rich repeat kinase 2 (LRRK2) has been associated with a variety of human diseases, including Parkinson's disease and Crohn's disease, whereas LRRK2 deficiency leads to accumulation of abnormal lysosomes in aged animals. However, the cellular roles and mechanisms of LRRK2-mediated lysosomal regulation have remained elusive. Here, we reveal a mechanism of stress-induced lysosomal response by LRRK2 and its target Rab GTPases. Lysosomal overload stress induced the recruitment of endogenous LRRK2 onto lysosomal membranes and activated LRRK2. An upstream adaptor Rab7L1 (Rab29) promoted the lysosomal recruitment of LRRK2. Subsequent family-wide screening of Rab GTPases that may act downstream of LRRK2 translocation revealed that Rab8a and Rab10 were specifically accumulated on overloaded lysosomes dependent on their phosphorylation by LRRK2. Rab7L1-mediated lysosomal targeting of LRRK2 attenuated the stress-induced lysosomal enlargement and promoted lysosomal secretion, whereas Rab8 stabilized by LRRK2 on stressed lysosomes suppressed lysosomal enlargement and Rab10 promoted lysosomal secretion, respectively. These effects were mediated by the recruitment of Rab8/10 effectors EHBP1 and EHBP1L1. LRRK2 deficiency augmented the chloroquine-induced lysosomal vacuolation of renal tubules in vivo. These results implicate the stress-responsive machinery composed of Rab7L1, LRRK2, phosphorylated Rab8/10, and their downstream effectors in the maintenance of lysosomal homeostasis.}, } @article {pmid30209219, year = {2018}, author = {Aguado, LC and Jordan, TX and Hsieh, E and Blanco-Melo, D and Heard, J and Panis, M and Vignuzzi, M and tenOever, BR}, title = {Homologous recombination is an intrinsic defense against antiviral RNA interference.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9211-E9219}, pmid = {30209219}, issn = {1091-6490}, support = {R01 AI110575/AI/NIAID NIH HHS/United States ; T32 AI007647/AI/NIAID NIH HHS/United States ; }, mesh = {A549 Cells ; Animals ; Homologous Recombination/*immunology ; Humans ; *Immunity, Innate ; Mice ; Mice, Knockout ; RNA Interference/*immunology ; RNA Virus Infections/genetics/*immunology ; RNA Viruses/*physiology ; RNA, Small Interfering/genetics/*immunology ; Virus Replication/genetics/*immunology ; }, abstract = {RNA interference (RNAi) is the major antiviral defense mechanism of plants and invertebrates, rendering the capacity to evade it a defining factor in shaping the viral landscape. Here we sought to determine whether different virus replication strategies provided any inherent capacity to evade RNAi in the absence of an antagonist. Through the exploitation of host microRNAs, we recreated an RNAi-like environment in vertebrates and directly compared the capacity of positive- and negative-stranded RNA viruses to cope with this selective pressure. Applying this defense against four distinct viral families revealed that the capacity to undergo homologous recombination was the defining attribute that enabled evasion of this defense. Independent of gene expression strategy, positive-stranded RNA viruses that could undergo strand switching rapidly excised genomic material, while negative-stranded viruses were effectively targeted and cleared upon RNAi-based selection. These data suggest a dynamic relationship between host antiviral defenses and the biology of virus replication in shaping pathogen prevalence.}, } @article {pmid30209218, year = {2018}, author = {Roemhild, R and Gokhale, CS and Dirksen, P and Blake, C and Rosenstiel, P and Traulsen, A and Andersson, DI and Schulenburg, H}, title = {Cellular hysteresis as a principle to maximize the efficacy of antibiotic therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9767-9772}, pmid = {30209218}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/*pharmacology/therapeutic use ; Dose-Response Relationship, Drug ; *Drug Resistance, Bacterial/genetics ; Drug Resistance, Multiple, Bacterial ; Evolution, Molecular ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa/drug effects/genetics ; Treatment Outcome ; }, abstract = {Antibiotic resistance has become one of the most dramatic threats to global health. While novel treatment options are urgently required, most attempts focus on finding new antibiotic substances. However, their development is costly, and their efficacy is often compromised within short time periods due to the enormous potential of microorganisms for rapid adaptation. Here, we developed a strategy that uses the currently available antibiotics. Our strategy exploits cellular hysteresis, which is the long-lasting, transgenerational change in cellular physiology that is induced by one antibiotic and sensitizes bacteria to another subsequently administered antibiotic. Using evolution experiments, mathematical modeling, genomics, and functional genetic analysis, we demonstrate that sequential treatment protocols with high levels of cellular hysteresis constrain the evolving bacteria by (i) increasing extinction frequencies, (ii) reducing adaptation rates, and (iii) limiting emergence of multidrug resistance. Cellular hysteresis is most effective in fast sequential protocols, in which antibiotics are changed within 12 h or 24 h, in contrast to the less frequent changes in cycling protocols commonly implemented in hospitals. We found that cellular hysteresis imposes specific selective pressure on the bacteria that disfavors resistance mutations. Instead, if bacterial populations survive, hysteresis is countered in two distinct ways, either through a process related to antibiotic tolerance or a mechanism controlled by the previously uncharacterized two-component regulator CpxS. We conclude that cellular hysteresis can be harnessed to optimize antibiotic therapy, to achieve both enhanced bacterial elimination and reduced resistance evolution.}, } @article {pmid30209217, year = {2018}, author = {Bottermann, M and Foss, S and van Tienen, LM and Vaysburd, M and Cruickshank, J and O'Connell, K and Clark, J and Mayes, K and Higginson, K and Hirst, JC and McAdam, MB and Slodkowicz, G and Hutchinson, E and Kozik, P and Andersen, JT and James, LC}, title = {TRIM21 mediates antibody inhibition of adenovirus-based gene delivery and vaccination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10440-10445}, pmid = {30209217}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; U105181010//Medical Research Council/United Kingdom ; U105178805//Medical Research Council/United Kingdom ; 172630//Medical Research Council/United Kingdom ; MR/N008618/1//Medical Research Council/United Kingdom ; }, mesh = {Adenoviridae/*immunology ; Adenoviridae Infections/genetics/immunology/*therapy ; Animals ; Antibodies/*immunology ; Fibrosarcoma/genetics/immunology/*therapy ; Gene Transfer Techniques ; *Genetic Therapy ; Genetic Vectors ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Ribonucleoproteins/*physiology ; Transgenes ; Tumor Cells, Cultured ; *Vaccination ; }, abstract = {Adenovirus has enormous potential as a gene-therapy vector, but preexisting immunity limits its widespread application. What is responsible for this immune block is unclear because antibodies potently inhibit transgene expression without impeding gene transfer into target cells. Here we show that antibody prevention of adenoviral gene delivery in vivo is mediated by the cytosolic antibody receptor TRIM21. Genetic KO of TRIM21 or a single-antibody point mutation is sufficient to restore transgene expression to near-naïve immune levels. TRIM21 is also responsible for blocking cytotoxic T cell induction by vaccine vectors, preventing a protective response against subsequent influenza infection and an engrafted tumor. Furthermore, adenoviral preexisting immunity can lead to an augmented immune response upon i.v. administration of the vector. Transcriptomic analysis of vector-transduced tissue reveals that TRIM21 is responsible for the specific up-regulation of hundreds of immune genes, the majority of which are components of the intrinsic or innate response. Together, these data define a major mechanism underlying the preimmune block to adenovirus gene therapy and demonstrate that TRIM21 efficiently blocks gene delivery in vivo while simultaneously inducing a rapid program of immune transcription.}, } @article {pmid30209216, year = {2018}, author = {Xue, L and Klinnawee, L and Zhou, Y and Saridis, G and Vijayakumar, V and Brands, M and Dörmann, P and Gigolashvili, T and Turck, F and Bucher, M}, title = {AP2 transcription factor CBX1 with a specific function in symbiotic exchange of nutrients in mycorrhizal Lotus japonicus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9239-E9246}, pmid = {30209216}, issn = {1091-6490}, mesh = {Fungal Proteins/*metabolism ; Lotus/genetics/*metabolism/microbiology ; Mycorrhizae/genetics/*metabolism ; Phosphate Transport Proteins/metabolism ; Phosphates/metabolism ; Proton-Translocating ATPases/metabolism ; *Symbiosis/genetics ; Transcription Factors/*metabolism ; }, abstract = {The arbuscular mycorrhizal (AM) symbiosis, a widespread mutualistic association between land plants and fungi, depends on reciprocal exchange of phosphorus driven by proton-coupled phosphate uptake into host plants and carbon supplied to AM fungi by host-dependent sugar and lipid biosynthesis. The molecular mechanisms and cis-regulatory modules underlying the control of phosphate uptake and de novo fatty acid synthesis in AM symbiosis are poorly understood. Here, we show that the AP2 family transcription factor CTTC MOTIF-BINDING TRANSCRIPTION FACTOR1 (CBX1), a WRINKLED1 (WRI1) homolog, directly binds the evolutionary conserved CTTC motif that is enriched in mycorrhiza-regulated genes and activates Lotus japonicus phosphate transporter 4 (LjPT4) in vivo and in vitro. Moreover, the mycorrhiza-inducible gene encoding H+-ATPase (LjHA1), implicated in energizing nutrient uptake at the symbiotic interface across the periarbuscular membrane, is coregulated with LjPT4 by CBX1. Accordingly, CBX1-defective mutants show reduced mycorrhizal colonization. Furthermore, genome-wide-binding profiles, DNA-binding studies, and heterologous expression reveal additional binding of CBX1 to AW box, the consensus DNA-binding motif for WRI1, that is enriched in promoters of glycolysis and fatty acid biosynthesis genes. We show that CBX1 activates expression of lipid metabolic genes including glycerol-3-phosphate acyltransferase RAM2 implicated in acylglycerol biosynthesis. Our finding defines the role of CBX1 as a regulator of host genes involved in phosphate uptake and lipid synthesis through binding to the CTTC/AW molecular module, and supports a model underlying bidirectional exchange of phosphorus and carbon, a fundamental trait in the mutualistic AM symbiosis.}, } @article {pmid30209215, year = {2018}, author = {Thinn, AMM and Wang, Z and Zhou, D and Zhao, Y and Curtis, BR and Zhu, J}, title = {Autonomous conformational regulation of β3 integrin and the conformation-dependent property of HPA-1a alloantibodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9105-E9114}, pmid = {30209215}, issn = {1091-6490}, support = {R01 HL131836/HL/NHLBI NIH HHS/United States ; R56 HL122985/HL/NHLBI NIH HHS/United States ; }, mesh = {Antibody Specificity ; Crystallography, X-Ray ; Glucuronidase/*chemistry/metabolism ; HEK293 Cells ; Humans ; Integrin alphaVbeta3/chemistry/metabolism ; Integrin beta3/*chemistry/metabolism ; Isoantibodies/*chemistry/metabolism ; Platelet Glycoprotein GPIIb-IIIa Complex/chemistry/metabolism ; Protein Domains ; Protein Folding ; }, abstract = {Integrin α/β heterodimer adopts a compact bent conformation in the resting state, and upon activation undergoes a large-scale conformational rearrangement. During the inside-out activation, signals impinging on the cytoplasmic tail of β subunit induce the α/β separation at the transmembrane and cytoplasmic domains, leading to the extended conformation of the ectodomain with the separated leg and the opening headpiece that is required for the high-affinity ligand binding. It remains enigmatic which integrin subunit drives the bent-to-extended conformational rearrangement in the inside-out activation. The β3 integrins, including αIIbβ3 and αVβ3, are the prototypes for understanding integrin structural regulation. The Leu33Pro polymorphism located at the β3 PSI domain defines the human platelet-specific alloantigen (HPA) 1a/b, which provokes the alloimmune response leading to clinically important bleeding disorders. Some, but not all, anti-HPA-1a alloantibodies can distinguish the αIIbβ3 from αVβ3 and affect their functions with unknown mechanisms. Here we designed a single-chain β3 subunit that mimics a separation of α/β heterodimer on inside-out activation. Our crystallographic and functional studies show that the single-chain β3 integrin folds into a bent conformation in solution but spontaneously extends on the cell surface. This demonstrates that the β3 subunit autonomously drives the membrane-dependent conformational rearrangement during integrin activation. Using the single-chain β3 integrin, we identified the conformation-dependent property of anti-HPA-1a alloantibodies, which enables them to differently recognize the β3 in the bent state vs. the extended state and in the complex with αIIb vs. αV This study provides deeper understandings of integrin conformational activation on the cell surface.}, } @article {pmid30209214, year = {2018}, author = {Niethard, N and Ngo, HV and Ehrlich, I and Born, J}, title = {Cortical circuit activity underlying sleep slow oscillations and spindles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9220-E9229}, pmid = {30209214}, issn = {1091-6490}, mesh = {Animals ; Biological Clocks/*physiology ; Calcium Signaling/*physiology ; Cerebral Cortex/cytology/*metabolism ; Interneurons/cytology/metabolism ; Mice ; Mice, Transgenic ; Microscopy, Fluorescence, Multiphoton ; Nerve Net/cytology/*metabolism ; Pyramidal Cells/cytology/metabolism ; Sleep Stages/*physiology ; }, abstract = {Slow oscillations and sleep spindles are hallmarks of the EEG during slow-wave sleep (SWS). Both oscillatory events, especially when co-occurring in the constellation of spindles nesting in the slow oscillation upstate, are considered to support memory formation and underlying synaptic plasticity. The regulatory mechanisms of this function at the circuit level are poorly understood. Here, using two-photon imaging in mice, we relate EEG-recorded slow oscillations and spindles to calcium signals recorded from the soma of cortical putative pyramidal-like (Pyr) cells and neighboring parvalbumin-positive interneurons (PV-Ins) or somatostatin-positive interneurons (SOM-Ins). Pyr calcium activity was increased more than threefold when spindles co-occurred with slow oscillation upstates compared with slow oscillations or spindles occurring in isolation. Independent of whether or not a spindle was nested in the slow oscillation upstate, the slow oscillation downstate was preceded by enhanced calcium signal in SOM-Ins that vanished during the upstate, whereas spindles were associated with strongly increased PV-In calcium activity. Additional wide-field calcium imaging of Pyr cells confirmed the enhanced calcium activity and its widespread topography associated with spindles nested in slow oscillation upstates. In conclusion, when spindles are nested in slow oscillation upstates, maximum Pyr activity appears to concur with strong perisomatic inhibition of Pyr cells via PV-Ins and low dendritic inhibition via SOM-Ins (i.e., conditions that might optimize synaptic plasticity within local cortical circuits).}, } @article {pmid30209213, year = {2018}, author = {Comeault, AA and Matute, DR}, title = {Genetic divergence and the number of hybridizing species affect the path to homoploid hybrid speciation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9761-9766}, pmid = {30209213}, issn = {1091-6490}, support = {R01 GM121750/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Crosses, Genetic ; Drosophila melanogaster/genetics ; Female ; *Genetic Drift ; *Genetic Speciation ; Hybridization, Genetic/*genetics ; Male ; Reproductive Isolation ; }, abstract = {Hybridization is often maladaptive and in some instances has led to the loss of biodiversity. However, hybridization can also promote speciation, such as during homoploid hybrid speciation, thereby generating biodiversity. Despite examples of homoploid hybrid species, the importance of hybridization as a speciation mechanism is still widely debated, and we lack a general understanding of the conditions most likely to generate homoploid hybrid species. Here we show that the level of genetic divergence between hybridizing species has a large effect on the probability that their hybrids evolve reproductive isolation. We find that populations of hybrids formed by parental species with intermediate levels of divergence were more likely to mate assortatively, and discriminate against their parental species, than those generated from weakly or strongly diverged parental species. Reproductive isolation was also found between hybrid populations, suggesting differential sorting of parental traits across populations. Finally, hybrid populations derived from three species were more likely to evolve reproductive isolation than those derived from two species, supporting arguments that hybridization-supplied genetic diversity can lead to the evolution of novel "adaptive systems" and promote speciation. Our results illustrate when we expect hybridization and admixture to promote hybrid speciation. Whether homoploid hybrid speciation is a common speciation mechanism in general remains an outstanding empirical question.}, } @article {pmid30209212, year = {2018}, author = {Garcia-Carbonell, R and Wong, J and Kim, JY and Close, LA and Boland, BS and Wong, TL and Harris, PA and Ho, SB and Das, S and Ernst, PB and Sasik, R and Sandborn, WJ and Bertin, J and Gough, PJ and Chang, JT and Kelliher, M and Boone, D and Guma, M and Karin, M}, title = {Elevated A20 promotes TNF-induced and RIPK1-dependent intestinal epithelial cell death.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9192-E9200}, pmid = {30209212}, issn = {1091-6490}, support = {R01 AI079145/AI/NIAID NIH HHS/United States ; R24 DK080506/DK/NIDDK NIH HHS/United States ; R56 AI079145/AI/NIAID NIH HHS/United States ; K08 AR064834/AR/NIAMS NIH HHS/United States ; R01 DK093507/DK/NIDDK NIH HHS/United States ; KL2 TR001444/TR/NCATS NIH HHS/United States ; //CIHR/Canada ; R01 AI043477/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Apoptosis ; Caspase 3/genetics/metabolism ; Caspase 8/genetics/metabolism ; Humans ; Inflammatory Bowel Diseases/genetics/*metabolism/pathology ; Intestinal Mucosa/*metabolism/pathology ; Mice ; Mice, Transgenic ; NF-kappa B/genetics/metabolism ; Protein Multimerization ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/*metabolism ; Tumor Necrosis Factor alpha-Induced Protein 3/genetics/*metabolism ; Tumor Necrosis Factor-alpha/genetics/*metabolism ; }, abstract = {Intestinal epithelial cell (IEC) death is a common feature of inflammatory bowel disease (IBD) that triggers inflammation by compromising barrier integrity. In many patients with IBD, epithelial damage and inflammation are TNF-dependent. Elevated TNF production in IBD is accompanied by increased expression of the TNFAIP3 gene, which encodes A20, a negative feedback regulator of NF-κB. A20 in intestinal epithelium from patients with IBD coincided with the presence of cleaved caspase-3, and A20 transgenic (Tg) mice, in which A20 is expressed from an IEC-specific promoter, were highly susceptible to TNF-induced IEC death, intestinal damage, and shock. A20-expressing intestinal organoids were also susceptible to TNF-induced death, demonstrating that enhanced TNF-induced apoptosis was a cell-autonomous property of A20. This effect was dependent on Receptor Interacting Protein Kinase 1 (RIPK1) activity, and A20 was found to associate with the Ripoptosome complex, potentiating its ability to activate caspase-8. A20-potentiated RIPK1-dependent apoptosis did not require the A20 deubiquitinase (DUB) domain and zinc finger 4 (ZnF4), which mediate NF-κB inhibition in fibroblasts, but was strictly dependent on ZnF7 and A20 dimerization. We suggest that A20 dimers bind linear ubiquitin to stabilize the Ripoptosome and potentiate its apoptosis-inducing activity.}, } @article {pmid30209211, year = {2018}, author = {Tecon, R and Ebrahimi, A and Kleyer, H and Erev Levi, S and Or, D}, title = {Cell-to-cell bacterial interactions promoted by drier conditions on soil surfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9791-9796}, pmid = {30209211}, issn = {1091-6490}, mesh = {Bacteria/metabolism ; Bacterial Physiological Phenomena ; Conjugation, Genetic ; Models, Theoretical ; Pseudomonas putida/metabolism/physiology ; *Soil Microbiology ; Water ; }, abstract = {Bacterial cell-to-cell interactions are in the core of evolutionary and ecological processes in soil and other environments. Under most conditions, natural soils are unsaturated where the fragmented aqueous habitats and thin liquid films confine bacterial cells within small volumes and close proximity for prolonged periods. We report effects of a range of hydration conditions on bacterial cell-level interactions that are marked by plasmid transfer between donor and recipient cells within populations of the soil bacterium Pseudomonas putida Using hydration-controlled sand microcosms, we demonstrate that the frequency of cell-to-cell contacts under prescribed hydration increases with lowering water potential values (i.e., under drier conditions where the aqueous phase shrinks and fragments). These observations were supported using a mechanistic individual-based model for linking macroscopic soil water potential to microscopic distribution of liquid phase and explicit bacterial cell interactions in a simplified porous medium. Model results are in good agreement with observations and inspire confidence in the underlying mechanisms. The study highlights important physical factors that control short-range bacterial cell interactions in soil and on surfaces, specifically, the central role of the aqueous phase in mediating bacterial interactions and conditions that promote genetic information transfer in support of soil microbial diversity.}, } @article {pmid30209011, year = {2018}, author = {Shade, A and Dunn, RR and Blowes, SA and Keil, P and Bohannan, BJM and Herrmann, M and Küsel, K and Lennon, JT and Sanders, NJ and Storch, D and Chase, J}, title = {Macroecology to Unite All Life, Large and Small.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {731-744}, doi = {10.1016/j.tree.2018.08.005}, pmid = {30209011}, issn = {1872-8383}, abstract = {Macroecology is the study of the mechanisms underlying general patterns of ecology across scales. Research in microbial ecology and macroecology have long been detached. Here, we argue that it is time to bridge the gap, as they share a common currency of species and individuals, and a common goal of understanding the causes and consequences of changes in biodiversity. Microbial ecology and macroecology will mutually benefit from a unified research agenda and shared datasets that span the entirety of the biodiversity of life and the geographic expanse of the Earth.}, } @article {pmid30209001, year = {2018}, author = {Oren, A and Garrity, GM}, title = {List of new names and new combinations previously effectively, but not validly, published.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2707-2709}, doi = {10.1099/ijsem.0.002945}, pmid = {30209001}, issn = {1466-5034}, } @article {pmid30208993, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 6, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2710-2711}, doi = {10.1099/ijsem.0.002853}, pmid = {30208993}, issn = {1466-5034}, } @article {pmid30208962, year = {2018}, author = {Yuan, J and Zhao, J and Wen, T and Zhao, M and Li, R and Goossens, P and Huang, Q and Bai, Y and Vivanco, JM and Kowalchuk, GA and Berendsen, RL and Shen, Q}, title = {Root exudates drive the soil-borne legacy of aboveground pathogen infection.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {156}, pmid = {30208962}, issn = {2049-2618}, abstract = {BACKGROUND: Plants are capable of building up beneficial rhizosphere communities as is evidenced by disease-suppressive soils. However, it is not known how and why soil bacterial communities are impacted by plant exposure to foliar pathogens and if such responses might improve plant performance in the presence of the pathogen. Here, we conditioned soil by growing multiple generations (five) of Arabidopsis thaliana inoculated aboveground with Pseudomonas syringae pv tomato (Pst) in the same soil. We then examined rhizosphere communities and plant performance in a subsequent generation (sixth) grown in pathogen-conditioned versus control-conditioned soil. Moreover, we assessed the role of altered root exudation profiles in shaping the root microbiome of infected plants.

RESULTS: Plants grown in conditioned soil showed increased levels of jasmonic acid and improved disease resistance. Illumina Miseq 16S rRNA gene tag sequencing revealed that both rhizosphere and bulk soil bacterial communities were altered by Pst infection. Infected plants exhibited significantly higher exudation of amino acids, nucleotides, and long-chain organic acids (LCOAs) (C > 6) and lower exudation levels for sugars, alcohols, and short-chain organic acids (SCOAs) (C ≤ 6). Interestingly, addition of exogenous amino acids and LCOA also elicited a disease-suppressive response.

CONCLUSION: Collectively, our data suggest that plants can recruit beneficial rhizosphere communities via modification of plant exudation patterns in response to exposure to aboveground pathogens to the benefit of subsequent plant generations.}, } @article {pmid30208953, year = {2018}, author = {Ramezani, A and Alipouratigh, M and Eng, L and Turkina, MV and Lönn, J and Theodorsson, A and Nayeri, F}, title = {One-minute through test to distinguish lower respiratory infection by analysis of sputum; exploring the mechanisms.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {664}, pmid = {30208953}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents ; Cough ; DNA/analysis ; Humans ; Respiratory Tract Infections/*diagnosis ; Sensitivity and Specificity ; Sputum/*microbiology ; Time Factors ; }, abstract = {OBJECTIVE: Cough and fever are the initial symptoms of lower respiratory infection. Severe cases might be fatal. Therefore, particularly in the non-equipped centers, the lack of diagnostic methods to identify the severe cases has resulted in overconsumption of antibiotics. On the basis of the knowledge about non-specific immune response at the site of injury, we developed a colorimetric dip-test that shows abrupt, sensitive and quite specific color change upon contact with sputum in the cases of lower respiratory infection. We further explored the mechanism of the test.

RESULTS: We detected deoxyribonucleic acid (DNA) and hepatocyte growth factor in the sputum of patients that suffered from respiratory infection (n = 18). The results differed significantly (P < 0.0001) from age-matched patients (n = 18) with other respiratory disorders and highly correlated with the index-test results (Spearman Rank test = 0.84). DNA with a concentration more than 0.03 mg/ml induced a visible and stable color change on index-test within 1 min. The test recognized all of the cases with respiratory infection and the specificity was 72%. With a high negative predictive value. The index test detects, inter alia, cell-free DNA in sputum and might safely rule-out respiratory infection in 2/3 of cases that present symptoms of acute respiratory infection.}, } @article {pmid30208952, year = {2018}, author = {Achek, R and Hotzel, H and Cantekin, Z and Nabi, I and Hamdi, TM and Neubauer, H and El-Adawy, H}, title = {Emerging of antimicrobial resistance in staphylococci isolated from clinical and food samples in Algeria.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {663}, pmid = {30208952}, issn = {1756-0500}, mesh = {Algeria ; Anti-Bacterial Agents ; *Drug Resistance, Bacterial ; *Food Microbiology ; Humans ; Microbial Sensitivity Tests ; Staphylococcal Infections ; Staphylococcus ; Staphylococcus aureus/*drug effects/isolation & purification ; }, abstract = {OBJECTIVE: The antimicrobial resistance of staphylococci rose worldwide. In total, 96 Staphylococcus isolates from food and clinical samples were collected from two provinces in Algeria. The antimicrobial susceptibility testing was performed and resistance-associated genes were detected.

RESULTS: Fifty-one strains were isolated from food samples and differentiated into 33 Staphylococcus aureus and 18 coagulase-negative staphylococci. Forty-five staphylococci were collected from hospital and community-acquired infection cases. All S. aureus isolated from food were resistant to penicillin and 45.5% were resistant to tetracycline. The resistance rates of 45 clinical Staphylococcus isolates were 86.7%, 48.9%, 37.8% and 20.0% to penicillin, tetracycline, erythromycin and kanamycin, respectively. Nine isolates were confirmed as MRSA from food and clinical isolates. One S. aureus originated from food was confirmed as vancomycin-resistant. Multidrug-resistance was observed among 25.5% and 53.3% of food and clinical staphylococci, respectively. The tetM/K, blaZ, aacA-aphD, ermC and mecA genes were detected in food and clinical isolates. ermA gene was not found. This study provided insight into the status of antimicrobial resistance of staphylococci isolated from food and clinical samples in Algeria. Further investigations and surveillance programmes are mandatory.}, } @article {pmid30208950, year = {2018}, author = {Ho, TTB and Groer, MW and Kane, B and Yee, AL and Torres, BA and Gilbert, JA and Maheshwari, A}, title = {Dichotomous development of the gut microbiome in preterm infants.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {157}, pmid = {30208950}, issn = {2049-2618}, support = {R01 HL133022/HL/NHLBI NIH HHS/United States ; R01 HL124078/HL/NHLBI NIH HHS/United States ; T32 GM007281/GM/NIGMS NIH HHS/United States ; R01 NR015446/NR/NINR NIH HHS/United States ; }, abstract = {BACKGROUND: Preterm infants are at risk of developing intestinal dysbiosis with an increased proportion of Gammaproteobacteria. In this study, we sought the clinical determinants of the relative abundance of feces-associated Gammaproteobacteria in very low birth weight (VLBW) infants. Fecal microbiome was characterized at ≤ 2 weeks and during the 3rd and 4th weeks after birth, by 16S rRNA amplicon sequencing. Maternal and infant clinical characteristics were extracted from electronic medical records. Data were analyzed by linear mixed modeling and linear regression.

RESULTS: Clinical data and fecal microbiome profiles of 45 VLBW infants (gestational age 27.9 ± 2.2 weeks; birth weight 1126 ± 208 g) were studied. Three stool samples were analyzed for each infant at mean postnatal ages of 9.9 ± 3, 20.7 ± 4.1, and 29.4 ± 4.9 days. The average relative abundance of Gammaproteobacteria was 42.5% (0-90%) at ≤ 2 weeks, 69.7% (29.9-86.9%) in the 3rd, and 75.5% (54.5-86%) in the 4th week (p < 0.001). Hierarchical and K-means clustering identified two distinct subgroups: cluster 1 started with comparatively low abundance that increased with time, whereas cluster 2 began with a greater abundance at ≤ 2 weeks (p < 0.001) that decreased over time. Both groups resembled each other by the 3rd week. Single variants of Klebsiella and Staphylococcus described variance in community structure between clusters and were shared between all infants, suggesting a common, hospital-derived source. Fecal Gammaproteobacteria was positively associated with vaginal delivery and antenatal steroids.

CONCLUSIONS: We detected a dichotomy in gut microbiome assembly in preterm infants: some preterm infants started with low relative gammaproteobacterial abundance in stool that increased as a function of postnatal age, whereas others began with and maintained high abundance. Vaginal birth and antenatal steroids were identified as predictors of Gammaproteobacteria abundance in the early (≤ 2 weeks) and later (3rd and 4th weeks) stool samples, respectively. These findings are important in understanding the development of the gut microbiome in premature infants.}, } @article {pmid30208946, year = {2018}, author = {Yanagawa, H and Katashima, R and Sato, C and Takechi, K and Nokihara, H and Kane, C and Chuma, M and Aoe, Y}, title = {Research ethics consultation: an attempt and 5-year experience in a Japanese University Hospital.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {665}, pmid = {30208946}, issn = {1756-0500}, support = {18oa0110003h0003//Japan Agency for Medical Research and Development, AMED/ ; }, mesh = {*Ethics Consultation ; *Hospitals, University ; Humans ; Japan ; }, abstract = {OBJECTIVE: Research ethics consultation is an advisory activity that differs from ethics committees, and its role is not yet widely known in Japan. Research ethics consultations were started in 2012 by members of the Clinical Trial Center of Tokushima University Hospital, a support section for clinical trials. We analyzed the research ethics consultation records from Tokushima University Hospital during the 5-year period of 2012-2016 to examine the Japanese context of research ethics consultation.

RESULTS: During the study period, 125 research ethics consultations were carried out, 115 (91%) before starting studies. All but one request were from investigators at Tokushima University. The main issue was compatibility with guidance and regulations (n = 74, 67.2%), such as ethical handling of human biological specimens and information utilized in research; only 6 (4.8%) requests involved research ethics issues that investigators face in their research. Therefore, it is necessary to expand the consultation function, with a nationwide system of consultant education and data sharing. Moreover, standardization of consultation should be considered.}, } @article {pmid30208944, year = {2018}, author = {Wang, Z and Yu, Q and Shen, W and El Mohtar, CA and Zhao, X and Gmitter, FG}, title = {Functional study of CHS gene family members in citrus revealed a novel CHS gene affecting the production of flavonoids.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {189}, pmid = {30208944}, issn = {1471-2229}, support = {00098334//Citrus Research and Development Foundation/ ; AWD02897//New varieties, Development and Management Corporation, on behalf of the Florida citrus growers/ ; B18044//111 project/ ; }, mesh = {Acetates/pharmacology ; Acyltransferases/genetics/*metabolism ; Citrus/drug effects/*enzymology/genetics ; Cyclopentanes/pharmacology ; Flavonoids/*biosynthesis ; Genes, Plant ; Multigene Family ; Oxylipins/pharmacology ; Phylogeny ; Plant Growth Regulators/pharmacology ; }, abstract = {BACKGROUND: Citrus flavonoids are considered as the important secondary metabolites because of their biological and pharmacological activities. Chalcone synthase (CHS) is a key enzyme that catalyses the first committed step in the flavonoid biosynthetic pathway. CHS genes have been isolated and characterized in many plants. Previous studies indicated that CHS is a gene superfamily. In citrus, the number of CHS members and their contribution to the production of flavonoids remains a mystery. In our previous study, the copies of CitCHS2 gene were found in different citrus species and the sequences are highly conserved, but the flavonoid content varied significantly among those species.

RESULTS: From seventy-seven CHS and CHS-like gene sequences, ten CHS members were selected as candidates according to the features of their sequences. Among these candidates, expression was detected from only three genes. A predicted CHS sequence was identified as a novel CHS gene. The structure analysis showed that the gene structure of this novel CHS is very similar to other CHS genes. All three CHS genes were highly conserved and had a basic structure that included one intron and two exons, although they had different expression patterns in different tissues and developmental stages. These genes also presented different sensitivities to methyl jasmonate (MeJA) treatment. In transgenic plants, the expression of CHS genes was significantly correlated with the production of flavonoids. The three CHS genes contributed differently to the production of flavonoids.

CONCLUSION: Our study indicated that CitCHS is a gene superfamily including at least three functional members. The expression levels of the CHS genes are highly correlated to the biosynthesis of flavonoids. The CHS enzyme is dynamically produced from several CHS genes, and the production of total flavonoids is regulated by the overall expression of CHS family genes.}, } @article {pmid30208918, year = {2018}, author = {Janus, JR and Voss, SG and Madden, BJ and Charlesworth, MC and Oldenburg, MS and Ekbom, D and San-Marina, S}, title = {Time-course mass spectrometry data of adipose mesenchymal stem cells acquiring chondrogenic phenotype.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {666}, pmid = {30208918}, issn = {1756-0500}, mesh = {Animals ; *Cell Differentiation ; *Chondrogenesis ; *Mass Spectrometry ; Mesenchymal Stem Cells/*physiology ; Phenotype ; Rabbits ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; }, abstract = {OBJECTIVES: Rabbit adipose mesenchymal stem cells were used for the purpose of studying acquisition of the chondrogenic phenotype over time at 1, 14 and 28 days after in vitro incubation with differentiation media, using nano-liquid chromatography electrospray ionization tandem mass spectrometry analysis. This was part of a preliminary study of the behavior of differentiated adipose stem cells for use in a rabbit model of laryngoplasty.

DATA DESCRIPTION: The data comprise .MGF, .RAW, .MZID, and .XLSX, lists of peaks, peptides and proteins identified by nano-flow liquid chromatography electrospray ionization tandem mass spectrometry analysis upon incubation with non-differentiating (ND) or chondrogenic differentiating (CHD) media (ProteomeXchange ID PXD010236). XLSX files contain the following information: day 1 CT (control, N = 3499 proteins), day 14 ND (N = 3106 proteins), day 28 ND (N = 3116 proteins), day 14 CHD (N = 2901 proteins), and day 28 CHD (N = 2876 proteins). Proteins are characterized with respect to their - 10lgP value, percent coverage, number of total as well as unique peptides after trypsin digestion, derivatization method (carbamidomethylation, oxidation, or combined carbamidomethylation + oxidation), average mass, and include a full description.}, } @article {pmid30208875, year = {2018}, author = {Wang, Q and Li, F and Liang, B and Liang, Y and Chen, S and Mo, X and Ju, Y and Zhao, H and Jia, H and Spector, TD and Xie, H and Guo, R}, title = {A metagenome-wide association study of gut microbiota in asthma in UK adults.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {114}, pmid = {30208875}, issn = {1471-2180}, support = {//Wellcome Trust/United Kingdom ; 105022/Z/14/Z//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Asthma, one of the most common chronic respiratory disorders, is associated with the hyper-activation of the T-cell subset of adaptive immunity. The gut microbiota may be involved in the development of asthma through the production of short-chain fatty acids (SCFAs), exhibiting modulatory effects on Th. So, we performed a metagenome-wide association study (MWAS) of the fecal microbiota from individuals with asthma and healthy controls. And that was the first case to resolve the relationship between asthma and microbiome among UK adults.

RESULTS: The microbiota of the individuals with asthma consisted of fewer microbial entities than the microbiota of healthy individuals. Faecalibacterium prausnitzii, Sutterella wadsworthensis and Bacteroides stercoris were depleted in cases, whereas Clostridiums with Eggerthella lenta were over-represented in individuals with asthma. Functional analysis shows that the SCFAs might be altered in the microbiota of asthma patients.

CONCLUSION: In all, the adult human gut microbiome of asthma patients is clearly different from healthy controls. The functional and taxa results showed that the change of asthma patients might related to SCFAs.}, } @article {pmid30208855, year = {2018}, author = {Klau, S and Jurinovic, V and Hornung, R and Herold, T and Boulesteix, AL}, title = {Priority-Lasso: a simple hierarchical approach to the prediction of clinical outcome using multi-omics data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {322}, pmid = {30208855}, issn = {1471-2105}, support = {2014.159.1//Wilhelm Sander-Stiftung/ ; BO3139/4-2//Deutsche Forschungsgemeinschaft/ ; 2014.159.1//Wilhelm Sander-Stiftung/ ; }, mesh = {Genomics/*methods ; Humans ; Kaplan-Meier Estimate ; Leukemia, Myeloid, Acute/genetics ; Reproducibility of Results ; Risk Factors ; *Software ; Treatment Outcome ; }, abstract = {BACKGROUND: The inclusion of high-dimensional omics data in prediction models has become a well-studied topic in the last decades. Although most of these methods do not account for possibly different types of variables in the set of covariates available in the same dataset, there are many such scenarios where the variables can be structured in blocks of different types, e.g., clinical, transcriptomic, and methylation data. To date, there exist a few computationally intensive approaches that make use of block structures of this kind.

RESULTS: In this paper we present priority-Lasso, an intuitive and practical analysis strategy for building prediction models based on Lasso that takes such block structures into account. It requires the definition of a priority order of blocks of data. Lasso models are calculated successively for every block and the fitted values of every step are included as an offset in the fit of the next step. We apply priority-Lasso in different settings on an acute myeloid leukemia (AML) dataset consisting of clinical variables, cytogenetics, gene mutations and expression variables, and compare its performance on an independent validation dataset to the performance of standard Lasso models.

CONCLUSION: The results show that priority-Lasso is able to keep pace with Lasso in terms of prediction accuracy. Variables of blocks with higher priorities are favored over variables of blocks with lower priority, which results in easily usable and transportable models for clinical practice.}, } @article {pmid30208853, year = {2018}, author = {Zhang, J and Li, Q and Qi, YP and Huang, WL and Yang, LT and Lai, NW and Ye, X and Chen, LS}, title = {Low pH-responsive proteins revealed by a 2-DE based MS approach and related physiological responses in Citrus leaves.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {188}, pmid = {30208853}, issn = {1471-2229}, support = {31772257//The National Natural Science Foundation of China/ ; CXZX2017232 and CXZX2016148//The earmarked fund for Science and Technology Innovation of Fujian Agriculture and Forestry University/ ; CARS27//The earmarked fund for China Agriculture Research System/ ; }, mesh = {Adaptation, Physiological ; Citrus/*metabolism ; Electrophoresis, Gel, Two-Dimensional ; Hydrogen-Ion Concentration ; Mass Spectrometry ; Plant Leaves/metabolism ; Plant Proteins/*metabolism ; Seedlings/metabolism ; }, abstract = {BACKGROUND: Rare data are available on the molecular responses of higher plants to low pH. Seedlings of 'Sour pummelo' (Citrus grandis) and 'Xuegan' (Citrus sinensis) were treated daily with nutrient solution at a pH of 2.5, 3, or 6 (control) for nine months. Thereafter, we first used 2-dimensional electrophoresis (2-DE) to investigate low pH-responsive proteins in Citrus leaves. Meanwhile, we examined low pH-effects on leaf gas exchange, carbohydrates, ascorbate, dehydroascorbate and malondialdehyde. The objectives were to understand the adaptive mechanisms of Citrus to low pH and to identify the possible candidate proteins for low pH-tolerance.

RESULTS: Our results demonstrated that Citrus were tolerant to low pH, with a slightly higher low pH-tolerance in the C. sinensis than in the C. grandis. Using 2-DE, we identified more pH 2.5-responsive proteins than pH 3-responsive proteins in leaves. This paper discussed mainly on the pH 2.5-responsive proteins. pH 2.5 decreased the abundances of proteins involved in ribulose bisphosphate carboxylase/oxygenase activation, Calvin cycle, carbon fixation, chlorophyll biosynthesis and electron transport, hence lowering chlorophyll level, electron transport rate and photosynthesis. The higher oxidative damage in the pH 2.5-treated C. grandis leaves might be due to a combination of factors including higher production of reactive oxygen species, more proteins decreased in abundance involved in antioxidation and detoxification, and lower ascorbate level. Protein and amino acid metabolisms were less affected in the C. sinensis leaves than those in the C. grandis leaves when exposed to pH 2.5. The abundances of proteins related to jasmonic acid biosynthesis and signal transduction were increased and decreased in the pH 2.5-treated C. sinensis and C. grandis leaves, respectively.

CONCLUSIONS: This is the first report on low pH-responsive proteins in higher plants. Thus, our results provide some novel information on low pH-toxicity and -tolerance in higher plants.}, } @article {pmid30208852, year = {2018}, author = {Khider, M and Willassen, NP and Hansen, H}, title = {The alternative sigma factor RpoQ regulates colony morphology, biofilm formation and motility in the fish pathogen Aliivibrio salmonicida.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {116}, pmid = {30208852}, issn = {1471-2180}, abstract = {BACKGROUND: Quorum sensing (QS) is a cell-to cell communication system that bacteria use to synchronize activities as a group. LitR, the master regulator of QS in Aliivibrio salmonicida, was recently shown to regulate activities such as motility, rugosity and biofilm formation in a temperature dependent manner. LitR was also found to be a positive regulator of rpoQ. RpoQ is an alternative sigma factor belonging to the sigma -70 family. Alternative sigma factors direct gene transcription in response to environmental signals. In this work we have studied the role of RpoQ in biofilm formation, colony morphology and motility of A. salmonicida LFI1238.

RESULTS: The rpoQ gene in A. salmonicida LFI1238 was deleted using allelic exchange. We found that RpoQ is a strong repressor of rugose colony morphology and biofilm formation, and that it controls motility of the bacteria. We also show that overexpression of rpoQ in a ΔlitR mutant of A. salmonicida disrupts the biofilm produced by the ΔlitR mutant and decreases its motility, whereas rpoQ overexpression in the wild-type completely eliminates the motility.

CONCLUSION: The present work demonstrates that the RpoQ sigma factor is a novel regulatory component involved in modulating motility, colony morphology and biofilm formation in the fish pathogen A. salmonicida. The findings also confirm that RpoQ functions downstream of the QS master regulator LitR. However further studies are needed to elucidate how LitR and RpoQ work together in controlling phenotypes related to QS in A. salmonicida.}, } @article {pmid30208849, year = {2018}, author = {Tiwari, SP and Tama, F and Miyashita, O}, title = {Searching for 3D structural models from a library of biological shapes using a few 2D experimental images.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {320}, pmid = {30208849}, issn = {1471-2105}, support = {KAKENHI 17K07305//Japan Society for the Promotion of Science/ ; KAKENHI 16K07286//Japan Society for the Promotion of Science/ ; KAKENHI 26119006//Japan Society for the Promotion of Science/ ; KAKENHI 15K21711//Japan Society for the Promotion of Science/ ; }, mesh = {Cluster Analysis ; Databases as Topic ; *Imaging, Three-Dimensional ; *Microscopy, Electron ; *Models, Molecular ; }, abstract = {BACKGROUND: Advancements in biophysical experimental techniques have pushed the limits in terms of the types of phenomena that can be characterized, the amount of data that can be produced and the resolution at which we can visualize them. Single particle techniques such as Electron Microscopy (EM) and X-ray free electron laser (XFEL) scattering require a large number of 2D images collected to resolve three-dimensional (3D) structures. In this study, we propose a quick strategy to retrieve potential 3D shapes, as low-resolution models, from a few 2D experimental images by searching a library of 2D projection images generated from existing 3D structures.

RESULTS: We developed the protocol to assemble a non-redundant set of 3D shapes for generating the 2D image library, and to retrieve potential match 3D shapes for query images, using EM data as a test. In our strategy, we disregard differences in volume size, giving previously unknown structures and conformations a greater number of 3D biological shapes as possible matches. We tested the strategy using images from three EM models as query images for searches against a library of 22750 2D projection images generated from 250 random EM models. We found that our ability to identify 3D shapes that match the query images depends on how complex the outline of the 2D shapes are and whether they are represented in the search image library.

CONCLUSIONS: Through our computational method, we are able to quickly retrieve a 3D shape from a few 2D projection images. Our approach has the potential for exploring other types of 2D single particle structural data such as from XFEL scattering experiments, for providing a tool to interpret low-resolution data that may be insufficient for 3D reconstruction, and for estimating the mixing of states or conformations that could exist in such experimental data.}, } @article {pmid30208848, year = {2018}, author = {Chen, L and Ding, X and Zhang, H and He, T and Li, Y and Wang, T and Li, X and Jin, L and Song, Q and Yang, S and Gai, J}, title = {Comparative analysis of circular RNAs between soybean cytoplasmic male-sterile line NJCMS1A and its maintainer NJCMS1B by high-throughput sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {663}, pmid = {30208848}, issn = {1471-2164}, support = {2016YFD0101500, 2016YFD0101504//the National Key R&D Program of China/ ; 2011AA10A105//the National Hightech R&D Program of China/ ; PCSIRT_17R55, PCSIRT13073//the Program for Changjiang Scholars and Innovative Research Team in University/ ; }, mesh = {Base Sequence ; Cytoplasm/*genetics ; Gene Expression Profiling ; Gene Ontology ; *High-Throughput Nucleotide Sequencing ; Plant Infertility/*genetics ; Pollen/growth & development ; RNA/*genetics ; *Sequence Analysis, RNA ; Soybeans/*cytology/*genetics/growth & development ; }, abstract = {BACKGROUND: Cytoplasmic male sterility (CMS) is a natural phenomenon of pollen abortion caused by the interaction between cytoplasmic genes and nuclear genes. CMS is a simple and effective pollination control system, and plays an important role in crop heterosis utilization. Circular RNAs (circRNAs) are a vital type of non-coding RNAs, which play crucial roles in microRNAs (miRNAs) function and post-transcription control. To explore the expression profile and possible functions of circRNAs in the soybean CMS line NJCMS1A and its maintainer NJCMS1B, high-throughput deep sequencing coupled with RNase R enrichment strategy was conducted.

RESULTS: CircRNA libraries were constructed from flower buds of NJCMS1A and its maintainer NJCMS1B with three biological replicates. A total of 2867 circRNAs were identified, with 1009 circRNAs differentially expressed between NJCMS1A and NJCMS1B based on analysis of high-throughput sequencing. Of the 12 randomly selected circRNAs with different expression levels, 10 showed consistent expression patterns based on high-throughput sequencing and quantitative real-time PCR analyses. Tissue specific expression patterns were also verified with two circRNAs by quantitative real-time PCR. Most parental genes of differentially expressed circRNAs were mainly involved in biological processes such as metabolic process, biological regulation, and reproductive process. Moreover, 83 miRNAs were predicted from the differentially expressed circRNAs, some of which were strongly related to pollen development and male fertility; The functions of miRNA targets were analyzed using Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the target mRNAs were significantly enriched in signal transduction and programmed cell death. Furthermore, a total of 165 soybean circRNAs were predicted to contain at least one internal ribosome entry site (IRES) element and an open reading frame, indicating their potential to encode polypeptides or proteins.

CONCLUSIONS: Our study indicated that the circRNAs might participate in the regulation of flower and pollen development, which could provide a new insight into the molecular mechanisms of CMS in soybean.}, } @article {pmid30208846, year = {2018}, author = {Wang, Z and Zhao, K and Pan, Y and Wang, J and Song, X and Ge, W and Yuan, M and Lei, T and Wang, L and Zhang, L and Li, Y and Liu, T and Chen, W and Meng, W and Sun, C and Cui, X and Bai, Y and Wang, X}, title = {Genomic, expressional, protein-protein interactional analysis of Trihelix transcription factor genes in Setaria italia and inference of their evolutionary trajectory.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {665}, pmid = {30208846}, issn = {1471-2164}, support = {QN2017123//Youth Foundation of Educational Committee of Hebei Province/ ; X2016161//Undergraduate Training Programs for Innovation and Entrepreneurship of North China University of Science and Technology/ ; 31371282//National Natural Science Foundation of China/ ; 31501072//National Natural Science Foundation of China/ ; C2016209097//National Science Foundation of Hebei province/ ; E2013100003//China-Hebei 100 Scholars Supporting Project/ ; }, mesh = {*Evolution, Molecular ; *Gene Expression Profiling ; *Genomics ; Phylogeny ; Plant Proteins/genetics/metabolism ; *Protein Interaction Mapping ; Selection, Genetic ; Sequence Alignment ; Setaria Plant/*genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {BACKGROUND: Trihelix transcription factors (TTF) play important roles in plant growth and response to adversity stress. Until now, genome-wide identification and analysis of this gene family in foxtail millet has not been available. Here, we identified TTF genes in the foxtail millet and its grass relatives, and characterized their functional domains.

RESULTS: As to sequence divergence, TTF genes were previously divided into five subfamilies, I-V. We found that Trihelix family members in foxtail millet and other grasses mostly preserved their ancestral chromosomal locations during millions of years' evolution. Six amino acid sites of the SIP1 subfamily possibly were likely subjected to significant positive selection. Highest expression level was observed in the spica, with the SIP1 subfamily having highest expression level. As to the origination and expansion of the gene family, notably we showed that a subgroup of subfamily IV was the oldest, and therefore was separated to define a new subfamily O. Overtime, starting from the subfamily O, certain genes evolved to form subfamilies III and I, and later from subfamily I to develop subfamilies II and V. The oldest gene, Si1g016284, has the most structural changes, and a high expression in different tissues. What's more interesting is that it may have bridge the interaction with different proteins.

CONCLUSIONS: By performing phylogenetic analysis using non-plant species, notably we showed that a subgroup of subfamily IV was the oldest, and therefore was separated to define a new subfamily O. Starting from the subfamily O, certain genes evolved to form other subfamilies. Our work will contribute to understanding the structural and functional innovation of Trihelix transcription factor, and the evolutionary trajectory.}, } @article {pmid30208844, year = {2018}, author = {Kosina, SM and Greiner, AM and Lau, RK and Jenkins, S and Baran, R and Bowen, BP and Northen, TR}, title = {Web of microbes (WoM): a curated microbial exometabolomics database for linking chemistry and microbes.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {115}, pmid = {30208844}, issn = {1471-2180}, abstract = {BACKGROUND: As microbiome research becomes increasingly prevalent in the fields of human health, agriculture and biotechnology, there exists a need for a resource to better link organisms and environmental chemistries. Exometabolomics experiments now provide assertions of the metabolites present within specific environments and how the production and depletion of metabolites is linked to specific microbes. This information could be broadly useful, from comparing metabolites across environments, to predicting competition and exchange of metabolites between microbes, and to designing stable microbial consortia. Here, we introduce Web of Microbes (WoM; freely available at: http://webofmicrobes.org), the first exometabolomics data repository and visualization tool.

DESCRIPTION: WoM provides manually curated, direct biochemical observations on the changes to metabolites in an environment after exposure to microorganisms. The web interface displays a number of key features: (1) the metabolites present in a control environment prior to inoculation or microbial activation, (2) heatmap-like displays showing metabolite increases or decreases resulting from microbial activities, (3) a metabolic web displaying the actions of multiple organisms on a specified metabolite pool, (4) metabolite interaction scores indicating an organism's interaction level with its environment, potential for metabolite exchange with other organisms and potential for competition with other organisms, and (5) downloadable datasets for integration with other types of -omics datasets.

CONCLUSION: We anticipate that Web of Microbes will be a useful tool for the greater research community by making available manually curated exometabolomics results that can be used to improve genome annotations and aid in the interpretation and construction of microbial communities.}, } @article {pmid30208843, year = {2018}, author = {Shpirer, E and Diamant, A and Cartwright, P and Huchon, D}, title = {A genome wide survey reveals multiple nematocyst-specific genes in Myxozoa.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {138}, pmid = {30208843}, issn = {1471-2148}, support = {2012768//NSF-BSF Joint Funding Programs in Integrative Organismal Systems (ICOB)/International ; IOS 1321759//NSF-BSF Joint Funding Programs in Integrative Organismal Systems (ICOB)/International ; }, mesh = {Animals ; Cnidaria/genetics ; Evolution, Molecular ; *Genome ; Myxozoa/*genetics ; Nematocyst/*parasitology ; Phylogeny ; Proteins/genetics ; Species Specificity ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Myxozoa represents a diverse group of microscopic endoparasites whose life cycle involves two hosts: a vertebrate (usually a fish) and an invertebrate (usually an annelid worm). Despite lacking nearly all distinguishing animal characteristics, given that each life cycle stage consists of no more than a few cells, molecular phylogenetic studies have revealed that myxozoans belong to the phylum Cnidaria, which includes corals, sea anemones, and jellyfish. Myxozoa, however, do possess a polar capsule; an organelle that is homologous to the stinging structure unique to Cnidaria: the nematocyst. Previous studies have identified in Myxozoa a number of protein-coding genes that are specific to nematocytes (the cells producing nematocysts) and thus restricted to Cnidaria. Determining which other genes are also homologous with the myxozoan polar capsule genes could provide insight into both the conservation and changes that occurred during nematocyst evolution in the transition to endoparasitism.

RESULTS: Previous studies have examined the phylogeny of two cnidarian-restricted gene families: minicollagens and nematogalectins. Here we identify and characterize seven additional cnidarian-restricted genes in myxozoan genomes using a phylogenetic approach. Four of the seven had never previously been identified as cnidarian-specific and none have been studied in a phylogenetic context. A majority of the proteins appear to be involved in the structure of the nematocyst capsule and tubule. No venom proteins were identified among the cnidarian-restricted genes shared by myxozoans.

CONCLUSIONS: Given the highly divergent forms that comprise Cnidaria, obtaining insight into the processes underlying their ancient diversification remains challenging. In their evolutionary transition to microscopic endoparasites, myxozoans lost nearly all traces of their cnidarian ancestry, with the one prominent exception being their nematocysts (or polar capsules). Thus nematocysts, and the genes that code for their structure, serve as rich sources of information to support the cnidarian origin of Myxozoa.}, } @article {pmid30208842, year = {2018}, author = {Yue, R and Lu, C and Han, X and Guo, S and Yan, S and Liu, L and Fu, X and Chen, N and Guo, X and Chi, H and Tie, S}, title = {Comparative proteomic analysis of maize (Zea mays L.) seedlings under rice black-streaked dwarf virus infection.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {191}, pmid = {30208842}, issn = {1471-2229}, support = {31571677//National Natural Science Foundation of China/ ; 2016YFD0101803//Molecular design breeding of Maize/ ; 2016YQ03//Science Foundation for The Excellent Youth Scholars of Henan Academy of Agricultural Sciences/ ; S2010-02-02//Industry technology system of Henan Province/ ; 0610032000//Supported by Research Program of Foundation and Advanced Technology of Henan Province/ ; }, mesh = {Plant Diseases/genetics/*virology ; Plant Proteins/*genetics ; Proteome ; *Reoviridae ; Seedlings/virology ; Zea mays/genetics/*virology ; }, abstract = {BACKGROUND: Maize rough dwarf disease (MRDD) is a severe disease that has been occurring frequently in southern China and many other Asian countries. MRDD is caused by the infection of Rice black streaked dwarf virus (RBSDV) and leads to significant economic losses in maize production. To well understand the destructive effects of RBSDV infection on maize growth, comparative proteomic analyses of maize seedlings under RBSDV infection was performed using an integrated approach involving LC-MS/MS and Tandem Mass Tag (TMT) labeling.

RESULTS: In total, 7615 maize proteins, 6319 of which were quantified. A total of 116 differentially accumulated proteins (DAPs) were identified, including 35 up- and 81 down-regulated proteins under the RBSDV infection. Enrichment analysis showed that the DAPs were most strongly associated with cyanoamino acid metabolism, protein processing in ER, and ribosome-related pathways. Two sulfur metabolism-related proteins were significantly reduced, indicating that sulfur may participate in the resistance against RBSDV infection. Furthermore, 15 DAPs involved in six metabolic pathways were identified in maize under the RBSDV infection.

CONCLUSIONS: Our data revealed that the responses of maize to RBSDV infection were controlled by various metabolic pathways.}, } @article {pmid30208841, year = {2018}, author = {Liu, Y and Wei, G and Xia, Y and Liu, X and Tang, J and Lu, Y and Lan, H and Zhang, S and Li, C and Cao, M}, title = {Comparative transcriptome analysis reveals that tricarboxylic acid cycle-related genes are associated with maize CMS-C fertility restoration.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {190}, pmid = {30208841}, issn = {1471-2229}, support = {2016YFD0101206//the National Key Research and Development Program of China/ ; 2016NZ0106//the Science and Technology Department of Sichuan Province/ ; }, mesh = {Citric Acid Cycle/*genetics ; Enzyme-Linked Immunosorbent Assay ; Fertility/genetics ; Gene Expression Profiling ; *Genes, Plant ; Plant Infertility/genetics ; Transcriptome ; Zea mays/*genetics/physiology ; }, abstract = {BACKGROUND: C-type cytoplasmic male sterility (CMS-C) is one of the three major types of cytoplasmic male sterility (CMS) in maize. Rf4 is a dominant restorer gene for CMS-C and has great value in hybrid maize breeding, but little information concerning its functional mechanism is known.

RESULTS: To reveal the functional mechanism of Rf4, we developed a pair of maize near-isogenic lines (NILs) for the Rf4 locus, which included a NIL_rf4 male-sterile line and a NIL_Rf4 male fertility-restored line. Genetic analysis and molecular marker detection indicated that the male fertility of NIL_Rf4 was controlled by Rf4. Whole-genome sequencing demonstrated genomic differences between the two NILs was clustered in the Rf4 mapping region. Unmapped reads of NILs were further assembled to uncover Rf4 candidates. RNA-Seq was then performed for the developing anthers of the NILs to identify critical genes and pathways associated with fertility restoration. A total of 7125 differentially expressed genes (DEGs) were identified. These DEGs were significantly enriched in 242 Gene Ontology (GO) categories, wherein 100 DEGs were involved in pollen tube development, pollen tube growth, pollen development, and gametophyte development. Homology analysis revealed 198 male fertility-related DEGs, and pathway enrichment analysis revealed that 58 DEGs were enriched in cell energy metabolism processes involved in glycolysis, the pentose phosphate pathway, and pyruvate metabolism. By querying the Plant Reactome Pathway database, we found that 14 of the DEGs were involved in the mitochondrial tricarboxylic acid (TCA) cycle and that most of them belonged to the isocitrate dehydrogenase (IDH) and oxoglutarate dehydrogenase (OGDH) enzyme complexes. Transcriptome sequencing and real-time quantitative PCR (qPCR) showed that all the above TCA cycle-related genes were up-regulated in NIL_Rf4. The results of our subsequent enzyme-linked immunosorbent assay (ELISA) experiments pointed out that the contents of both the IDH and OGDH enzymes accumulated more in the spikelets of NIL_Rf4 than in those of NIL_rf4.

CONCLUSION: The present research provides valuable genomic resources for deep insight into the molecular mechanism underlying CMS-C male fertility restoration. Importantly, our results indicated that genes involved in energy metabolism, especially some mitochondrial TCA cycle-related genes, were associated with maize CMS-C male fertility restoration.}, } @article {pmid30208840, year = {2018}, author = {Zhang, S and Zhang, H and Xia, Y and Xiong, L}, title = {The caseinolytic protease complex component CLPC1 in Arabidopsis maintains proteome and RNA homeostasis in chloroplasts.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {192}, pmid = {30208840}, issn = {1471-2229}, support = {BAS/1/1007-01-01//King Abdullah University of Science and Technology/ ; 12100717//Research Grants Council, University Grants Committee/ ; frg2/16-17/026//Hong Kong Baptist University/ ; SDF 15-1012-P04//Hong Kong Baptist University/ ; AoE/M-403/16//University Research Committee, University of Hong Kong/ ; }, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Chloroplast Proteins/genetics/*metabolism ; Chloroplasts/genetics/*metabolism ; Genes, Plant ; Heat-Shock Proteins/genetics/*metabolism ; Homeostasis ; Mutation ; Proteome ; RNA, Plant/*metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Homeostasis of the proteome is critical to the development of chloroplasts and also affects the expression of certain nuclear genes. CLPC1 facilitates the translocation of chloroplast pre-proteins and mediates protein degradation.

RESULTS: We found that proteins involved in photosynthesis are dramatically decreased in their abundance in the clpc1 mutant, whereas many proteins involved in chloroplast transcription and translation were increased in the mutant. Expression of the full-length CLPC1 protein, but not of the N-terminus-deleted CLPC1 (ΔN), in the clpc1 mutant background restored the normal levels of most of these proteins. Interestingly, the ΔN complementation line could also restore some proteins affected by the mutation to normal levels. We also found that that the clpc1 mutation profoundly affects transcript levels of chloroplast genes. Sense transcripts of many chloroplast genes are up-regulated in the clpc1 mutant. The level of SVR7, a PPR protein, was affected by the clpc1 mutation. We showed that SVR7 might be a target of CLPC1 as CLPC1-SVR7 interaction was detected through co-immunoprecipitation.

CONCLUSION: Our study indicates that in addition to its role in maintaining proteome homeostasis, CLPC1 and likely the CLP proteasome complex also play a role in transcriptome homeostasis through its functions in maintaining proteome homeostasis.}, } @article {pmid30208839, year = {2018}, author = {Bono, JM and Pigage, HK and Wettstein, PJ and Prosser, SA and Pigage, JC}, title = {Genome-wide markers reveal a complex evolutionary history involving divergence and introgression in the Abert's squirrel (Sciurus aberti) species group.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {139}, pmid = {30208839}, issn = {1471-2148}, mesh = {Animals ; *Biological Evolution ; Cytochromes b/genetics ; DNA, Mitochondrial/genetics ; Genetic Markers ; *Genetic Variation ; *Genome ; Geography ; Haplotypes/genetics ; Likelihood Functions ; Mitochondria/genetics ; Phylogeography ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; Sciuridae/*genetics ; }, abstract = {BACKGROUND: Genetic introgression between divergent lineages is now considered more common than previously appreciated, with potentially important consequences for adaptation and speciation. Introgression is often asymmetric between populations and patterns can vary for different types of loci (nuclear vs. organellar), complicating phylogeographic reconstruction. The taxonomy of the ecologically specialized Abert's squirrel species group has been controversial, and previous studies based on mitochondrial data have not fully resolved the evolutionary relationships among populations. Moreover, while these studies identified potential areas of secondary contact between divergent lineages, the possibility for introgression has not been tested.

RESULTS: We used RAD-seq to unravel the complex evolutionary history of the Abert's squirrel species group. Although some of our findings reinforce inferences based on mitochondrial data, we also find significant areas of discordance. Discordant signals generally arise from previously undetected introgression between divergent populations that differentially affected variation at mitochondrial and nuclear loci. Most notably, our results support earlier claims (disputed by mitochondrial data) that S. aberti kaibabensis, found only on the north rim of the Grand Canyon, is highly divergent from other populations. However, we also detected introgression of S. aberti kaibabensis DNA into other S. aberti populations, which likely accounts for the previously inferred close genetic relationship between this population and those south of the Grand Canyon.

CONCLUSIONS: Overall, the evolutionary history of Abert's squirrels appears to be shaped largely by divergence during periods of habitat isolation. However, we also found evidence for interbreeding during periods of secondary contact resulting in introgression, with variable effects on mitochondrial and nuclear markers. Our results support the emerging view that populations often diversify under scenarios involving both divergence in isolation and gene flow during secondary contact, and highlight the value of genome-wide datasets for resolving such complex evolutionary histories.}, } @article {pmid30208838, year = {2018}, author = {Müller, R and Nebel, ME}, title = {GeFaST: An improved method for OTU assignment by generalising Swarm's fastidious clustering approach.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {321}, pmid = {30208838}, issn = {1471-2105}, mesh = {*Algorithms ; Cluster Analysis ; Databases as Topic ; High-Throughput Nucleotide Sequencing/*methods ; RNA, Ribosomal, 16S/genetics ; Time Factors ; }, abstract = {BACKGROUND: Massive genomic data sets from high-throughput sequencing allow for new insights into complex biological systems such as microbial communities. Analyses of their diversity and structure are typically preceded by clustering millions of 16S rRNA gene sequences into OTUs. Swarm introduced a new clustering strategy which addresses important conceptual and performance issues of the popular de novo clustering approach. However, some parts of the new strategy, e.g. the fastidious option for increased clustering quality, come with their own restrictions.

RESULTS: In this paper, we present the new exact, alignment-based de novo clustering tool GeFaST, which implements a generalisation of Swarm's fastidious clustering. Our tool extends the fastidious option to arbitrary clustering thresholds and allows to adjust its greediness. GeFaST was evaluated on mock-community and natural data and achieved higher clustering quality and performance for small to medium clustering thresholds compared to Swarm and other de novo tools. Clustering with GeFaST was between 6 and 197 times as fast as with Swarm, while the latter required up to 38% less memory for non-fastidious clustering but at least three times as much memory for fastidious clustering.

CONCLUSIONS: GeFaST extends the scope of Swarm's clustering strategy by generalising its fastidious option, thereby allowing for gains in clustering quality, and by increasing its performance (especially in the fastidious case). Our evaluations showed that GeFaST has the potential to leverage the use of the (fastidious) clustering strategy for higher thresholds and on larger data sets.}, } @article {pmid30208837, year = {2018}, author = {Xia, C and Wang, M and Yin, C and Cornejo, OE and Hulbert, SH and Chen, X}, title = {Genomic insights into host adaptation between the wheat stripe rust pathogen (Puccinia striiformis f. sp. tritici) and the barley stripe rust pathogen (Puccinia striiformis f. sp. hordei).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {664}, pmid = {30208837}, issn = {1471-2164}, support = {2090-22000-018-00D//Agricultural Research Service/ ; 13C-3061-5682//Washington Grain Commission/ ; }, mesh = {Adaptation, Physiological/*genetics ; Basidiomycota/*genetics/*physiology ; Evolution, Molecular ; *Genomics ; Hordeum/microbiology ; Host-Pathogen Interactions/*genetics ; Plant Diseases/*microbiology ; Repetitive Sequences, Nucleic Acid/genetics ; Telomere/genetics ; Triticum/microbiology ; }, abstract = {BACKGROUND: Plant fungal pathogens can rapidly evolve and adapt to new environmental conditions in response to sudden changes of host populations in agro-ecosystems. However, the genomic basis of their host adaptation, especially at the forma specialis level, remains unclear.

RESULTS: We sequenced two isolates each representing Puccinia striiformis f. sp. tritici (Pst) and P. striiformis f. sp. hordei (Psh), different formae speciales of the stripe rust fungus P. striiformis highly adapted to wheat and barley, respectively. The divergence of Pst and Psh, estimated to start 8.12 million years ago, has been driven by high nucleotide mutation rates. The high genomic variation within dikaryotic urediniospores of P. striiformis has provided raw genetic materials for genome evolution. No specific gene families have enriched in either isolate, but extensive gene loss events have occurred in both Pst and Psh after the divergence from their most recent common ancestor. A large number of isolate-specific genes were identified, with unique genomic features compared to the conserved genes, including 1) significantly shorter in length; 2) significantly less expressed; 3) significantly closer to transposable elements; and 4) redundant in pathways. The presence of specific genes in one isolate (or forma specialis) was resulted from the loss of the homologues in the other isolate (or forma specialis) by the replacements of transposable elements or losses of genomic fragments. In addition, different patterns and numbers of telomeric repeats were observed between the isolates.

CONCLUSIONS: Host adaptation of P. striiformis at the forma specialis level is a complex pathogenic trait, involving not only virulence-related genes but also other genes. Gene loss, which might be adaptive and driven by transposable element activities, provides genomic basis for host adaptation of different formae speciales of P. striiformis.}, } @article {pmid30208294, year = {2018}, author = {Opachaloemphan, C and Yan, H and Leibholz, A and Desplan, C and Reinberg, D}, title = {Recent Advances in Behavioral (Epi)Genetics in Eusocial Insects.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {489-510}, doi = {10.1146/annurev-genet-120116-024456}, pmid = {30208294}, issn = {1545-2948}, abstract = {Eusocial insects live in societies in which distinct family members serve specific roles in maintaining the colony and advancing the reproductive ability of a few select individuals. Given the genetic similarity of all colony members, the diversity of morphologies and behaviors is surprising. Social communication relies on pheromones and olfaction, as shown by mutants of orco, the universal odorant receptor coreceptor, and through electrophysiological analysis of neuronal responses to pheromones. Additionally, neurohormonal factors and epigenetic regulators play a key role in caste-specific behavior, such as foraging and caste switching. These studies start to allow an understanding of the molecular mechanisms underlying social behavior and provide a technological foundation for future studies of eusocial insects. In this review, we highlight recent findings in eusocial insects that advance our understanding of genetic and epigenetic regulations of social behavior and provide perspectives on future studies using cutting-edge technologies.}, } @article {pmid30208293, year = {2018}, author = {Sedelnikova, OV and Hughes, TE and Langdale, JA}, title = {Understanding the Genetic Basis of C4 Kranz Anatomy with a View to Engineering C3 Crops.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {249-270}, doi = {10.1146/annurev-genet-120417-031217}, pmid = {30208293}, issn = {1545-2948}, abstract = {One of the most remarkable examples of convergent evolution is the transition from C3 to C4 photosynthesis, an event that occurred on over 60 independent occasions. The evolution of C4 is particularly noteworthy because of the complexity of the developmental and metabolic changes that took place. In most cases, compartmentalized metabolic reactions were facilitated by the development of a distinct leaf anatomy known as Kranz. C4 Kranz anatomy differs from ancestral C3 anatomy with respect to vein spacing patterns across the leaf, cell-type specification around veins, and cell-specific organelle function. Here we review our current understanding of how Kranz anatomy evolved and how it develops, with a focus on studies that are dissecting the underlying genetic mechanisms. This research field has gained prominence in recent years because understanding the genetic regulation of Kranz may enable the C3-to-C4 transition to be engineered, an endeavor that would significantly enhance crop productivity.}, } @article {pmid30208292, year = {2018}, author = {de Lange, T}, title = {Shelterin-Mediated Telomere Protection.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {223-247}, doi = {10.1146/annurev-genet-032918-021921}, pmid = {30208292}, issn = {1545-2948}, abstract = {For more than a decade, it has been known that mammalian cells use shelterin to protect chromosome ends. Much progress has been made on the mechanism by which shelterin prevents telomeres from inadvertently activating DNA damage signaling and double-strand break (DSB) repair pathways. Shelterin averts activation of three DNA damage response enzymes [the ataxia-telangiectasia-mutated (ATM) and ataxia telangiectasia and Rad3-related (ATR) kinases and poly(ADP-ribose) polymerase 1 (PARP1)], blocks three DSB repair pathways [classical nonhomologous end joining (c-NHEJ), alternative (alt)-NHEJ, and homology-directed repair (HDR)], and prevents hyper-resection at telomeres. For several of these functions, mechanistic insights have emerged. In addition, much has been learned about how shelterin maintains the telomeric 3' overhang, forms and protects the t-loop structure, and promotes replication through telomeres. These studies revealed that shelterin is compartmentalized, with individual subunits dedicated to distinct aspects of the end-protection problem. This review focuses on the current knowledge of shelterin-mediated telomere protection, highlights differences between human and mouse shelterin, and discusses some of the questions that remain.}, } @article {pmid30208291, year = {2018}, author = {Mertens, J and Reid, D and Lau, S and Kim, Y and Gage, FH}, title = {Aging in a Dish: iPSC-Derived and Directly Induced Neurons for Studying Brain Aging and Age-Related Neurodegenerative Diseases.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {271-293}, doi = {10.1146/annurev-genet-120417-031534}, pmid = {30208291}, issn = {1545-2948}, support = {R01 AG056306/AG/NIA NIH HHS/United States ; }, abstract = {Age-associated neurological diseases represent a profound challenge in biomedical research as we are still struggling to understand the interface between the aging process and the manifestation of disease. Various pathologies in the elderly do not directly result from genetic mutations, toxins, or infectious agents but are primarily driven by the many manifestations of biological aging. Therefore, the generation of appropriate model systems to study human aging in the nervous system demands new concepts that lie beyond transgenic and drug-induced models. Although access to viable human brain specimens is limited and induced pluripotent stem cell models face limitations due to reprogramming-associated cellular rejuvenation, the direct conversion of somatic cells into induced neurons allows for the generation of human neurons that capture many aspects of aging. Here, we review advances in exploring age-associated neurodegenerative diseases using human cell reprogramming models, and we discuss general concepts, promises, and limitations of the field.}, } @article {pmid30208290, year = {2018}, author = {Seeber, A and Hauer, MH and Gasser, SM}, title = {Chromosome Dynamics in Response to DNA Damage.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {295-319}, doi = {10.1146/annurev-genet-120417-031334}, pmid = {30208290}, issn = {1545-2948}, abstract = {Recent advances in both the technologies used to measure chromatin movement and the biophysical analysis used to model them have yielded a fuller understanding of chromatin dynamics and the polymer structure that underlies it. Changes in nucleosome packing, checkpoint kinase activation, the cell cycle, chromosomal tethers, and external forces acting on nuclei in response to external and internal stimuli can alter the basal mobility of DNA in interphase nuclei of yeast or mammalian cells. Although chromatin movement is assumed to be necessary for many DNA-based processes, including gene activation by distal enhancer-promoter interaction or sequence-based homology searches during double-strand break repair, experimental evidence supporting an essential role in these activities is sparse. Nonetheless, high-resolution tracking of chromatin dynamics has led to instructive models of the higher-order folding and flexibility of the chromatin polymer. Key regulators of chromatin motion in physiological conditions or after damage induction are reviewed here.}, } @article {pmid30208289, year = {2018}, author = {Gomes-Filho, JV and Daume, M and Randau, L}, title = {Unique Archaeal Small RNAs.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {465-487}, doi = {10.1146/annurev-genet-120417-031300}, pmid = {30208289}, issn = {1545-2948}, abstract = {Advances in genome-wide sequence technologies allow for detailed insights into the complexity of RNA landscapes of organisms from all three domains of life. Recent analyses of archaeal transcriptomes identified interaction and regulation networks of noncoding RNAs in this understudied domain. Here, we review current knowledge of small, noncoding RNAs with important functions for the archaeal lifestyle, which often requires adaptation to extreme environments. One focus is RNA metabolism at elevated temperatures in hyperthermophilic archaea, which reveals elevated amounts of RNA-guided RNA modification and virus defense strategies. Genome rearrangement events result in unique fragmentation patterns of noncoding RNA genes that require elaborate maturation pathways to yield functional transcripts. RNA-binding proteins, e.g., L7Ae and LSm, are important for many posttranscriptional control functions of RNA molecules in archaeal cells. We also discuss recent insights into the regulatory potential of their noncoding RNA partners.}, } @article {pmid30208288, year = {2018}, author = {Pancaroglu, R and Van Petegem, F}, title = {Calcium Channelopathies: Structural Insights into Disorders of the Muscle Excitation-Contraction Complex.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {373-396}, doi = {10.1146/annurev-genet-120417-031311}, pmid = {30208288}, issn = {1545-2948}, abstract = {Ion channels are membrane proteins responsible for the passage of ions down their electrochemical gradients and across biological membranes. In this, they generate and shape action potentials and provide secondary messengers for various signaling pathways. They are often part of larger complexes containing auxiliary subunits and regulatory proteins. Channelopathies arise from mutations in the genes encoding ion channels or their associated proteins. Recent advances in cryo-electron microscopy have resulted in an explosion of ion channel structures in multiple states, generating a wealth of new information on channelopathies. Disease-associated mutations fall into different categories, interfering with ion permeation, protein folding, voltage sensing, ligand and protein binding, and allosteric modulation of channel gating. Prime examples of these are Ca2+-selective channels expressed in myocytes, for which multiple structures in distinct conformational states have recently been uncovered. We discuss the latest insights into these calcium channelopathies from a structural viewpoint.}, } @article {pmid30208287, year = {2018}, author = {Stanley, SY and Maxwell, KL}, title = {Phage-Encoded Anti-CRISPR Defenses.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {445-464}, doi = {10.1146/annurev-genet-120417-031321}, pmid = {30208287}, issn = {1545-2948}, abstract = {The battle for survival between bacteria and bacteriophages (phages) is an arms race where bacteria develop defenses to protect themselves from phages and phages evolve counterstrategies to bypass these defenses. CRISPR-Cas adaptive immune systems represent a widespread mechanism by which bacteria protect themselves from phage infection. In response to CRISPR-Cas, phages have evolved protein inhibitors known as anti-CRISPRs. Here, we describe the discovery and mechanisms of action of anti-CRISPR proteins. We discuss the potential impact of anti-CRISPRs on bacterial evolution, speculate on their evolutionary origins, and contemplate the possible next steps in the CRISPR-Cas evolutionary arms race. We also touch on the impact of anti-CRISPRs on the development of CRISPR-Cas-based biotechnological tools.}, } @article {pmid30207517, year = {2018}, author = {Kumar, S and Singh, H and Kaur, M and Kaur, L and Tanuku, NRS and Pinnaka, AK}, title = {Bacillus shivajii sp. nov., isolated from a water sample of Sambhar salt lake, India.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3463-3470}, doi = {10.1099/ijsem.0.003008}, pmid = {30207517}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; India ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phosphatidylglycerols/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; }, abstract = {A novel Gram-stain-positive, rod-shaped, motile, spore-forming, strictly aerobic, alkali- and halo- tolerant bacterium, designated strain AK72T, was isolated from a water sample collected from Sambhar salt lake, Rajasthan, India. The colony appears circular, shiny, smooth, translucent or slightly pale in colour and convex with an entire margin after 48 h incubation at 37 °C with pH 9. Growth of the bacterium occurred at 10-42 °C (optimum, 25-37 °C), at salinities of 0.5-10 % (w/v) NaCl (optimum 3-5 % NaCl) and pH of 6-10 (optimum pH 9). Strain AK72T was positive for oxidase, catalase, nitrate reductase, phenylalanine deaminase, ornithine decarboxylase, aesculinase, lipase and urease activities. The predominant fatty acids were iso-C15 : 0, anteiso-C15 : 0 and iso-C16 : 0 and the cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The major polar lipids of the strain were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminophospholipid, three unidentified phospholipids and three unidentified lipids. The genomic DNA G+C content of the strain AK72T was 36.8 mol%. Phylogenetic analysis of the 16S rRNA gene sequence indicated that strain AK72T was closely related to Bacillus cellulosilyticus (96.5 %) and Bacillus vedderi (96.3 %), but the novel strain AK72T formed a separate clade with Bacillus aurantiacus whereas B. cellulosilyticus and B. vedderi were clustered in a separate clade. The above data in combination with the phenotypic characteristics and phylogenetic data inferred that strain AK72T represents a novel species of the genus Bacillus, for which the name Bacillusshivajii sp. nov. is proposed. The type strain is AK72T (=MTCC 12636T=KCTC 33981T=JCM 32183T).}, } @article {pmid30207516, year = {2018}, author = {Ke, Z and Yang, MJ and Jia, WB and Mu, Y and Li, JL and Chen, D and Chen, K and Jiang, JD}, title = {Chitinophaga parva sp. nov., a new member of the family Chitinophagaceae, isolated from soil in a chemical factory.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3452-3457}, doi = {10.1099/ijsem.0.003006}, pmid = {30207516}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; *Chemical Industry ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative bacterium, designated LY-1T, was isolated from the soil sample collected from a chemical factory in Fuyang city, Anhui province, China. Cells of strain LY-1T were strictly aerobic, non-motile and rod-shaped. Strain LY-1T grew optimally at pH 7.0 and at 30-35 °C. The taxonomic position was investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain LY-1T was a member of the genus Chitinophaga and showed the highest sequence similarity to Chitinophaga costaii A37T2T (97.5 %) and lower (<97.0 %) sequence similarity to other known Chitinophaga species. Chemotaxonomic analysis revealed that strain LY-1T possessed menaquinone-7 as the major isoprenoid quinone; and iso-C15 : 0 (46.4 %), C16 : 1ω5c (27.8 %) and iso-C17 : 0 3-OH (9.0 %) were the predominant fatty acids. The polar lipids of strain LY-1T consisted of phosphatidylethanolamine, three unidentified phosphoaminolipids, one unidentified phospholipid, four unidentified lipids, two unidentified aminolipids and two unidentified glycolipids. The genomic DNA G+C content of strain LY-1T was 52.4 mol% based on total genome calculations. The average nucleotide identity and the digital DNA-DNA hybridization value of the draft genomes between strain LY-1T and strain A37T2T were 76.8 and 19.8 %, respectively. Based on the phylogenetic and phenotypic characteristics, chemotaxonomic data, and DNA-DNA hybridization, strain LY-1T is considered a novel species of the genus Chitinophaga, for which the name Chitinophagaparva sp. nov. (type strain LY-1T=CCTCC AB 2018018T=KCTC 62444T) is proposed.}, } @article {pmid30207068, year = {2018}, author = {Dunon, V and Bers, K and Lavigne, R and Top, EM and Springael, D}, title = {Targeted metagenomics demonstrates the ecological role of IS1071 in bacterial community adaptation to pesticide degradation.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {4091-4111}, doi = {10.1111/1462-2920.14404}, pmid = {30207068}, issn = {1462-2920}, support = {//IWT-Vlaanderen Strategic Basic Research project 91370/ ; G.0371.06//Fonds Wetenschappelijk Onderzoek (FWO)/ ; 222625//EU project METAEXPLORE/ ; }, abstract = {IS1071, an insertion element that primarily flanks organic xenobiotic degradation genes in cultured isolates, is suggested to play a key role in the formation and distribution of bacterial catabolic pathway gene clusters. However, in environmental settings, the identity of the IS1071 genetic cargo and its correspondence to the local selective conditions remain unknown. To respond, we developed a long-range PCR approach amplifying accessory genes between two IS1071 copies from community DNA followed by amplicon sequencing. We applied this method to pesticide-exposed environments, i.e. linuron-treated agricultural soil and on-farm biopurification systems (BPS) treating complex agricultural wastewater, as to non-treated controls. Amplicons were mainly recovered from the pesticide-exposed environments and the BPS matrix showed a higher size diversity compared to the agricultural soil. Retrieved gene functions mirrored the main selection pressure as (i) a large fraction of the BPS amplicons contained a high variety of genes/gene clusters related to the degradation of organics including herbicides present in the wastewater and (ii) in the agricultural soil, recovered genes were associated with linuron degradation. Our metagenomic analysis extends observations from cultured isolates and provides evidence that IS1071 is a carrier of catabolic genes in xenobiotica stressed environments and contributes to community level adaptation towards pesticide biodegradation.}, } @article {pmid30206668, year = {2018}, author = {Li, Z and Liu, X and Liu, R and Li, L and Wang, L and Wang, W}, title = {Insight into Bacterial Community Diversity and Monthly Fluctuations of Medicago sativa Rhizosphere Soil in Response to Hydrogen Gas Using Illumina High-Throughput Sequencing.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {30206668}, issn = {1432-0991}, support = {41571243//National Natural Science Foundation of China/ ; 20160232//The project of young talents of science and technology association of shaanxi province/ ; }, abstract = {The microbial diversity and the monthly fluctuations in Medicago sativa field soil in response to hydrogen gas were investigated. Illumina high-throughput sequencing was used to analyze the bacteria in raw and hydrogen-treated rhizosphere soil. Among the 18 soil samples, the abundance change of the predominant phyla Proteobacteria and Actinobacteria showed opposite trends. The diversity index analysis of the nine leguminous soil samples showed the highest diversity of the microbial community in July. In the other nine soil samples treated with hydrogen, the microbial diversity decreased and the diversity of soil microorganisms in September was higher than that in July, but not significantly so. The heat map analysis revealed that the microbial community composition of the soil samples was different before and after the hydrogen treatment. After the soil samples were treated with hydrogen, the dominant genera were Nocardioide, Pseudomonas, Janibacter, Microbacterium, Microvirga, Streptomyces, and Phenylobacterium in May; Bradyrhizobium, Haliangium, Sphingomonas, Blastocatella, Lysobacter, and Sphingopyxis in July; and Aeromicrobium, Pseudonocardia, Lentzea, and Skermanella in September. This study indicates that time and hydrogen gas have significant effects on the diversity of microbes in M. sativa rhizospheric soil.}, } @article {pmid30206667, year = {2018}, author = {Dashevsky, D and Debono, J and Rokyta, D and Nouwens, A and Josh, P and Fry, BG}, title = {Three-Finger Toxin Diversification in the Venoms of Cat-Eye Snakes (Colubridae: Boiga).}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {30206667}, issn = {1432-1432}, abstract = {The Asian genus Boiga (Colubridae) is among the better studied non-front-fanged snake lineages, because their bites have minor, but noticeable, effects on humans. Furthermore, B. irregularis has gained worldwide notoriety for successfully invading Guam and other nearby islands with drastic impacts on the local bird populations. One of the factors thought to allow B. irregularis to become such a noxious pest is irditoxin, a dimeric neurotoxin composed of two three-finger toxins (3FTx) joined by a covalent bond between two newly evolved cysteines. Irditoxin is highly toxic to diapsid (birds and reptiles) prey, but roughly 1000 × less potent to synapsids (mammals). Venom plays an important role in the ecology of all species of Boiga, but it remains unknown if any species besides B. irregularis produce irditoxin-like dimeric toxins. In this study, we use transcriptomic analyses of venom glands from five species [B. cynodon, B. dendrophila dendrophila, B. d. gemmicincta, B. irregularis (Brisbane population), B. irregularis (Sulawesi population), B. nigriceps, B. trigonata] and proteomic analyses of B. d. dendrophila and a representative of the sister genus Toxicodryas blandingii to investigate the evolutionary history of 3FTx within Boiga and its close relative. We found that 92.5% of Boiga 3FTx belong to a single clade which we refer to as denmotoxin-like because of the close relation between these toxins and the monomeric denmotoxin according to phylogenetic, sequence clustering, and protein similarity network analyses. We show for the first time that species beyond B. irregularis secrete 3FTx with additional cysteines in the same position as both the A and B subunits of irditoxin. Transcripts with the characteristic mutations are found in B. d. dendrophila, B. d. gemmicincta, B. irregularis (Brisbane population), B. irregularis (Sulawesi population), and B. nigriceps. These results are confirmed by proteomic analyses that show direct evidence of dimerization within the venom of B. d. dendrophila, but not T. blandingii. Our results also suggest the possibility of novel dimeric toxins in other genera such as Telescopus and Trimorphodon. All together, this suggests that the origin of these peculiar 3FTx is far earlier than was appreciated and their evolutionary history has been complex.}, } @article {pmid30206666, year = {2018}, author = {Dangwal, M and Das, S}, title = {Identification and Analysis of OVATE Family Members from Genome of the Early Land Plants Provide Insights into Evolutionary History of OFP Family and Function.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {30206666}, issn = {1432-1432}, support = {F.4-2/2006 (BSR)/BL/16-17/0032//University Grants Commission/ ; }, abstract = {Mosses, liverworts, hornworts and lycophytes represent transition stages between the aquatic to terrestrial/land plants. Several morphological and adaptive novelties driven by genomic components including emergence and expansion of new or existing gene families have played a critical role during and after the transition, and contributed towards successful colonization of terrestrial ecosystems. It is crucial to decipher the evolutionary transitions and natural selection on the gene structure and function to understand the emergence of phenotypic and adaptive diversity. Plants at the "transition zone", between aquatic and terrestrial ecosystem, are also the most vulnerable because of climate change and may contain clues for successful mitigation of the challenges of climate change. Identification and comparative analyses of such genetic elements and gene families are few in mosses, liverworts, hornworts and lycophytes. Ovate family proteins (OFPs) are plant-specific transcriptional repressors and are acknowledged for their roles in important growth and developmental processes in land plants, and information about the functional aspects of OFPs in early land plants is fragmentary. As a first step towards addressing this gap, a comprehensive in silico analysis was carried out utilizing publicly available genome sequences of Marchantia polymorpha (Mp), Physcomitrella patens (Pp), Selaginella moellendorffii (Sm) and Sphagnum fallax (Sf). Our analysis led to the identification of 4 MpOFPs, 19 PpOFPs, 6 SmOFPs and 3 SfOFPs. Cross-genera analysis revealed a drastic change in the structure and physiochemical properties in OFPs suggesting functional diversification and genomic plasticity during the evolutionary course. Knowledge gained from this comparative analysis will form the framework towards deciphering and dissection of their developmental and adaptive role/s in early land plants and could provide insights into evolutionary strategies adapted by land plants.}, } @article {pmid30206403, year = {2018}, author = {}, title = {Pakistan's prosperity needs independent experts.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {150}, doi = {10.1038/d41586-018-06659-9}, pmid = {30206403}, issn = {1476-4687}, mesh = {Advisory Committees/*organization & administration ; *Federal Government ; Pakistan ; Politics ; Science/economics/*organization & administration/*standards ; }, } @article {pmid30206402, year = {2018}, author = {Cohen, M}, title = {Post-crash economics: have we learnt nothing?.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {151}, doi = {10.1038/d41586-018-06608-6}, pmid = {30206402}, issn = {1476-4687}, } @article {pmid30206401, year = {2018}, author = {Sohn, E}, title = {A fieldwork flop needn't be a disaster.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {275-277}, doi = {10.1038/d41586-018-06618-4}, pmid = {30206401}, issn = {1476-4687}, } @article {pmid30206400, year = {2018}, author = {Schmidgen, H}, title = {The last polymath.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {175}, doi = {10.1038/d41586-018-06613-9}, pmid = {30206400}, issn = {1476-4687}, } @article {pmid30206399, year = {2018}, author = {Weinberger, S}, title = {The long entanglement of war and astrophysics.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {173-174}, doi = {10.1038/d41586-018-06612-w}, pmid = {30206399}, issn = {1476-4687}, } @article {pmid30206398, year = {2018}, author = {}, title = {Caches of mummified penguins warn of climate-change impacts.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {152}, doi = {10.1038/d41586-018-06181-y}, pmid = {30206398}, issn = {1476-4687}, } @article {pmid30206397, year = {2018}, author = {Reardon, S}, title = {Raging wildfires send scientists scrambling to study health effects.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {157-158}, doi = {10.1038/d41586-018-06123-8}, pmid = {30206397}, issn = {1476-4687}, } @article {pmid30206396, year = {2018}, author = {}, title = {How to warn of a pulsating artery that could burst any time.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {152}, doi = {10.1038/d41586-018-06209-3}, pmid = {30206396}, issn = {1476-4687}, } @article {pmid30206395, year = {2018}, author = {}, title = {'Molecular sieve' offers inexpensive way to sift plastic's raw materials.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {152-153}, doi = {10.1038/d41586-018-06203-9}, pmid = {30206395}, issn = {1476-4687}, } @article {pmid30206394, year = {2018}, author = {}, title = {Meagre ranks of anti-flu drugs look set to grow.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {153}, doi = {10.1038/d41586-018-06184-9}, pmid = {30206394}, issn = {1476-4687}, } @article {pmid30206393, year = {2018}, author = {}, title = {The stars that team up to push planets to their death.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {153}, doi = {10.1038/d41586-018-06174-x}, pmid = {30206393}, issn = {1476-4687}, } @article {pmid30206392, year = {2018}, author = {Wild, S}, title = {South Africa pushes science to improve daily life.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {158-159}, doi = {10.1038/d41586-018-06122-9}, pmid = {30206392}, issn = {1476-4687}, } @article {pmid30206391, year = {2018}, author = {Merali, Z}, title = {Pulsar discoverer Jocelyn Bell Burnell wins $3-million Breakthrough Prize.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {161}, doi = {10.1038/d41586-018-06210-w}, pmid = {30206391}, issn = {1476-4687}, mesh = {*Astronomical Phenomena ; *Awards and Prizes ; History, 20th Century ; History, 21st Century ; Nobel Prize ; *Research Personnel/statistics & numerical data ; Sexism/*prevention & control ; }, } @article {pmid30206390, year = {2018}, author = {Castelvecchi, D}, title = {Google unveils search engine for open data.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {161-162}, doi = {10.1038/d41586-018-06201-x}, pmid = {30206390}, issn = {1476-4687}, mesh = {*Access to Information ; Algorithms ; *Datasets as Topic ; Facilities and Services Utilization/trends ; *Industry ; *Internet ; Open Access Publishing ; Research Personnel ; *Search Engine ; }, } @article {pmid30206389, year = {2018}, author = {}, title = {The world's first flexitarian shark grazes like a cow.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {152}, doi = {10.1038/d41586-018-06173-y}, pmid = {30206389}, issn = {1476-4687}, } @article {pmid30206388, year = {2018}, author = {Kumar, S}, title = {India's surprise plan to send people to space by 2022.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {160}, doi = {10.1038/d41586-018-06146-1}, pmid = {30206388}, issn = {1476-4687}, mesh = {*Astronauts ; Humans ; India ; Politics ; Space Flight/economics/*trends ; Time Factors ; }, } @article {pmid30206387, year = {2018}, author = {}, title = {Skin bacterium learns to shrug off antibiotic of last resort.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {153}, doi = {10.1038/d41586-018-06172-z}, pmid = {30206387}, issn = {1476-4687}, } @article {pmid30206344, year = {2018}, author = {Field, MC and Horn, D and Fairlamb, AH and Ferguson, MAJ and Gray, DW and Read, KD and De Rycker, M and Torrie, LS and Wyatt, PG and Wyllie, S and Gilbert, IH}, title = {Author Correction: Anti-trypanosomatid drug discovery: an ongoing challenge and a continuing need.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {714}, doi = {10.1038/s41579-018-0085-1}, pmid = {30206344}, issn = {1740-1534}, abstract = {The structures of nifurtimox in Table 1 were incorrect and have been updated in the pdf and online. The authors apologize for any confusion caused.}, } @article {pmid30206153, year = {2018}, author = {Dasbiswas, K and Mandadapu, KK and Vaikuntanathan, S}, title = {Topological localization in out-of-equilibrium dissipative systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9031-E9040}, pmid = {30206153}, issn = {1091-6490}, support = {R01 GM110066/GM/NIGMS NIH HHS/United States ; }, mesh = {*Hydrodynamics ; *Models, Theoretical ; }, abstract = {In this paper, we report that notions of topological protection can be applied to stationary configurations that are driven far from equilibrium by active, dissipative processes. We consider two physically disparate systems: stochastic networks governed by microscopic single-particle dynamics, and collections of driven interacting particles described by coarse-grained hydrodynamic theory. We derive our results by mapping to well-known electronic models and exploiting the resulting correspondence between a bulk topological number and the spectrum of dissipative modes localized at the boundary. For the Markov networks, we report a general procedure to uncover the topological properties in terms of the transition rates. For the active fluid on a substrate, we introduce a topological interpretation of fluid dissipative modes at the edge. In both cases, the presence of dissipative couplings to the environment that break time-reversal symmetry are crucial to ensuring topological protection. These examples constitute proof of principle that notions of topological protection do indeed extend to dissipative processes operating out of equilibrium. Such topologically robust boundary modes have implications for both biological and synthetic systems.}, } @article {pmid30206152, year = {2018}, author = {Carlin, AF and Vizcarra, EA and Branche, E and Viramontes, KM and Suarez-Amaran, L and Ley, K and Heinz, S and Benner, C and Shresta, S and Glass, CK}, title = {Deconvolution of pro- and antiviral genomic responses in Zika virus-infected and bystander macrophages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9172-E9181}, pmid = {30206152}, issn = {1091-6490}, support = {R21 NS100477/NS/NINDS NIH HHS/United States ; P01 DK074868/DK/NIDDK NIH HHS/United States ; R21 AI127988/AI/NIAID NIH HHS/United States ; R01 DK091183/DK/NIDDK NIH HHS/United States ; KL2 TR001444/TR/NCATS NIH HHS/United States ; R01 AI116813/AI/NIAID NIH HHS/United States ; }, mesh = {Bystander Effect ; Female ; Humans ; *Immunity, Innate ; Interferon-beta/genetics/immunology ; Macrophages/*immunology/pathology ; Male ; Proteolysis ; RNA Polymerase II/genetics/immunology ; STAT2 Transcription Factor/genetics/immunology ; Zika Virus/*immunology ; Zika Virus Infection/*immunology/pathology ; }, abstract = {Genome-wide investigations of host-pathogen interactions are often limited by analyses of mixed populations of infected and uninfected cells, which lower sensitivity and accuracy. To overcome these obstacles and identify key mechanisms by which Zika virus (ZIKV) manipulates host responses, we developed a system that enables simultaneous characterization of genome-wide transcriptional and epigenetic changes in ZIKV-infected and neighboring uninfected primary human macrophages. We demonstrate that transcriptional responses in ZIKV-infected macrophages differed radically from those in uninfected neighbors and that studying the cell population as a whole produces misleading results. Notably, the uninfected population of macrophages exhibits the most rapid and extensive changes in gene expression, related to type I IFN signaling. In contrast, infected macrophages exhibit a delayed and attenuated transcriptional response distinguished by preferential expression of IFNB1 at late time points. Biochemical and genomic studies of infected macrophages indicate that ZIKV infection causes both a targeted defect in the type I IFN response due to degradation of STAT2 and reduces RNA polymerase II protein levels and DNA occupancy, particularly at genes required for macrophage identity. Simultaneous evaluation of transcriptomic and epigenetic features of infected and uninfected macrophages thereby reveals the coincident evolution of dominant proviral or antiviral mechanisms, respectively, that determine the outcome of ZIKV exposure.}, } @article {pmid30206151, year = {2018}, author = {Blanco-Elorrieta, E and Emmorey, K and Pylkkänen, L}, title = {Language switching decomposed through MEG and evidence from bimodal bilinguals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9708-9713}, pmid = {30206151}, issn = {1091-6490}, support = {R01 DC010997/DC/NIDCD NIH HHS/United States ; R01 HD047736/HD/NICHD NIH HHS/United States ; }, mesh = {Brain/*physiology ; Cognition/physiology ; Executive Function/physiology ; Humans ; Language ; *Magnetoencephalography ; *Multilingualism ; *Sign Language ; }, abstract = {A defining feature of human cognition is the ability to quickly and accurately alternate between complex behaviors. One striking example of such an ability is bilinguals' capacity to rapidly switch between languages. This switching process minimally comprises disengagement from the previous language and engagement in a new language. Previous studies have associated language switching with increased prefrontal activity. However, it is unknown how the subcomputations of language switching individually contribute to these activities, because few natural situations enable full separation of disengagement and engagement processes during switching. We recorded magnetoencephalography (MEG) from American Sign Language-English bilinguals who often sign and speak simultaneously, which allows to dissociate engagement and disengagement. MEG data showed that turning a language "off" (switching from simultaneous to single language production) led to increased activity in the anterior cingulate cortex (ACC) and dorsolateral prefrontal cortex (dlPFC), while turning a language "on" (switching from one language to two simultaneously) did not. The distinct representational nature of these on and off processes was also supported by multivariate decoding analyses. Additionally, Granger causality analyses revealed that (i) compared with "turning on" a language, "turning off" required stronger connectivity between left and right dlPFC, and (ii) dlPFC activity predicted ACC activity, consistent with models in which the dlPFC is a top-down modulator of the ACC. These results suggest that the burden of language switching lies in disengagement from the previous language as opposed to engaging a new language and that, in the absence of motor constraints, producing two languages simultaneously is not necessarily more cognitively costly than producing one.}, } @article {pmid30206150, year = {2018}, author = {Rappe, AM}, title = {Ionic gating drives correlated insulator-metal transition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9655-9657}, pmid = {30206150}, issn = {1091-6490}, mesh = {Coordination Complexes ; Ionic Liquids ; *Ions ; *Metals ; Micro-Electrical-Mechanical Systems ; Surface Properties ; }, } @article {pmid30206146, year = {2018}, author = {Kwok, R}, title = {Science and Culture: Raw data videos offer a glimpse into laboratory research.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9048-9050}, doi = {10.1073/pnas.1813373115}, pmid = {30206146}, issn = {1091-6490}, mesh = {Animals ; *Biomedical Research ; Humans ; *Motion Pictures ; }, } @article {pmid30205080, year = {2018}, author = {Jeffery, WR}, title = {Progenitor targeting by adult stem cells in Ciona homeostasis, injury, and regeneration.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.09.005}, pmid = {30205080}, issn = {1095-564X}, support = {R01 AG055411/AG/NIA NIH HHS/United States ; }, abstract = {In the ascidian Ciona intestinalis, oral siphon amputation activates adult stem cell niches in the branchial sac to divide and dispatch migratory progenitor cells to a regeneration blastema at the site of injury. This study shows that progenitor cells derived from branchial sac stem cell niches have roles in homeostasis, wound repair, and regeneration of the siphons and neural complex (NC). During homeostasis, progenitor cells targeted the pharyngeal stigmata to replace ciliated cells involved in filter feeding. After individual or double siphon amputations, progenitor cells specifically targeted the oral or atrial siphons or both siphons, and were involved in the replacement of siphon circular muscle fibers. After oral siphon wounding, progenitor cells targeted the wound sites, and in some cases a supernumerary siphon was formed, although progenitor cell targeting did not predict the induction of supernumerary siphons. Following NC ablation, progenitor cells specifically targeted the regenerating NC, and supplied the precursors of new brain and neural gland cells. The tissues and organs targeted by branchial sac stem cells exhibited apoptosis during homeostasis and injury. It is concluded that branchial sac progenitor cells are multipotent and show targeting specificity that is correlated with apoptosis during homeostatic growth, tissue repair, and regeneration.}, } @article {pmid30205032, year = {2018}, author = {Audzijonyte, A and Richards, SA}, title = {The Energetic Cost of Reproduction and Its Effect on Optimal Life-History Strategies.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {E150-E162}, doi = {10.1086/698655}, pmid = {30205032}, issn = {1537-5323}, abstract = {Trade-offs in energy allocation between growth, reproduction, and survival are at the core of life-history theory. While age-specific mortality is considered to be the main determinant of the optimal allocation, some life-history strategies, such as delayed or skipped reproduction, may be better understood when also accounting for reproduction costs. Here, we present a two-pool indeterminate grower model that includes survival and energetic costs of reproduction. The energetic cost sets a minimum reserve required for reproduction, while the survival cost reflects increased mortality from low postreproductive body condition. Three life-history parameters determining age-dependent energy allocation to soma, reserve, and reproduction are optimized, and we show that the optimal strategies can reproduce realistic emergent growth trajectories, maturation ages, and reproductive outputs for fish. The model predicts maturation phase shifts along the gradient of condition-related mortality and shows that increased harvesting will select for earlier maturation and higher energy allocation to reproduction. However, since the energetic reproduction cost sets limits on how early an individual can mature, an increase in fitness at high harvesting can only be achieved by diverting most reserves into reproduction. The model presented here can improve predictions of life-history responses to environmental change and human impacts because key life-history traits such as maturation age and size, maximum body size, and size-specific fecundity emerge dynamically.}, } @article {pmid30205031, year = {2018}, author = {Becker, DJ and Snedden, CE and Altizer, S and Hall, RJ}, title = {Host Dispersal Responses to Resource Supplementation Determine Pathogen Spread in Wildlife Metapopulations.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {503-517}, doi = {10.1086/699477}, pmid = {30205031}, issn = {1537-5323}, abstract = {Many wildlife species occupy landscapes that vary in the distribution, abundance, and quality of food resources. Increasingly, urbanized and agricultural habitats provide supplemental food resources that can have profound consequences for host distributions, movement patterns, and pathogen exposure. Understanding how host and pathogen dispersal across landscapes is affected by the spatial extent of food-supplemented habitats is therefore important for predicting the consequences for pathogen spread and impacts on host occupancy. Here we develop a generalizable metapopulation model to understand how the relative abundance of provisioned habitats across the landscape and how the host dispersal responses to provisioning and infection influence patch occupancy by hosts and their pathogens. We find that pathogen invasion and landscape-level infection prevalence are greatest when provisioning increases patch attractiveness and disperser production and when infection has minimal costs on dispersal success. Alternatively, if provisioning promotes site fidelity or reduces disperser production, increasing the fraction of food-supplemented habitats can reduce landscape-scale infection prevalence and minimize disease-induced declines in host occupancy. This work highlights the importance of considering how resources and infection jointly influence host dispersal for predicting how changing resource distributions influence the spread of infectious diseases.}, } @article {pmid30205030, year = {2018}, author = {Singhal, S and Huang, H and Grundler, MR and Marchán-Rivadeneira, MR and Holmes, I and Title, PO and Donnellan, SC and Rabosky, DL}, title = {Does Population Structure Predict the Rate of Speciation? A Comparative Test across Australia's Most Diverse Vertebrate Radiation.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {432-447}, doi = {10.1086/699515}, pmid = {30205030}, issn = {1537-5323}, abstract = {Population divergence is the first step in allopatric speciation, as has long been recognized in both theoretical models of speciation and empirical explorations of natural systems. All else being equal, lineages with substantial population differentiation should form new species more quickly than lineages that maintain range-wide genetic cohesion through high levels of gene flow. However, there have been few direct tests of the extent to which population differentiation predicts speciation rates as measured on phylogenetic trees. Here, we explicitly test the links between organismal traits, population-level processes, and phylogenetic speciation rates across a diverse clade of Australian lizards that shows remarkable variation in speciation rate. Using genome-wide double digest restriction site-associated DNA data from 892 individuals, we generated a comparative data set on isolation by distance and population differentiation across 104 putative species-level lineages (operational taxonomic units). We find that species show substantial variation in the extent of population differentiation, and this variation is predicted by organismal traits that are thought to be proxies for dispersal and deme size. However, variation in population structure does not predict variation in speciation rate. Our results suggest that population differentiation is not the rate-limiting step in species formation and that other ecological and historical factors are primary determinants of speciation rates at macroevolutionary scales.}, } @article {pmid30205029, year = {2018}, author = {Nuismer, SL and Week, B and Aizen, MA}, title = {Coevolution Slows the Disassembly of Mutualistic Networks.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {490-502}, doi = {10.1086/699218}, pmid = {30205029}, issn = {1537-5323}, abstract = {Important groups of mutualistic species are threatened worldwide, and identifying factors that make them more or less fragile in the face of disturbance is becoming increasingly critical. Although much research has focused on identifying the ecological factors that favor the stability of communities rich in mutualists, much less has been devoted to understanding the role played by historical and contemporary evolution. Here we develop mathematical models and computer simulations of coevolving mutualistic communities that allow us to explore the importance of coevolution in stabilizing communities against anthropogenic disturbance. Our results demonstrate that communities with a long history of coevolution are substantially more robust to disturbance, losing individual species and interactions at lower rates. In addition, our results identify a novel phenomenon-coevolutionary rescue-that mitigates the impacts of ongoing anthropogenic disturbance by rewiring the network structure of the community in a way that compensates for the extinction of individual species and interactions.}, } @article {pmid30205028, year = {2018}, author = {Berger, V and Lemaître, JF and Allainé, D and Gaillard, JM and Cohas, A}, title = {Early and Adult Social Environments Shape Sex-Specific Actuarial Senescence Patterns in a Cooperative Breeder.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {525-536}, doi = {10.1086/699513}, pmid = {30205028}, issn = {1537-5323}, abstract = {Sociality modulates life-history traits through changes in resource allocation to fitness-related traits. However, how social factors at different stages of the life cycle modulate senescence remains poorly understood. To address this question, we assessed the influence of social environment in both early life and adulthood on actuarial senescence in the Alpine marmot, a cooperative breeder. The influence of helpers on actuarial senescence strongly differed depending on when help was provided and on the sex of the dominant. Being helped when adult slowed down senescence in both sexes. However, the effect of the presence of helpers during the year of birth of a dominant was sex specific. Among dominants helped during adulthood, females born in the presence of helpers senesced slower, whereas males senesced faster. Among dominants without helpers during adulthood, females with helpers at birth senesced faster. Social environment modulates senescence but acts differently between sexes and life stages.}, } @article {pmid30205027, year = {2018}, author = {Wheatcroft, D and Price, TD}, title = {Collective Action Promoted by Key Individuals.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {401-414}, doi = {10.1086/698874}, pmid = {30205027}, issn = {1537-5323}, abstract = {Explaining why individuals participate in risky group behaviors has been a long-term challenge. We experimentally studied the formation of groups of birds (mobs) that aggressively confront predators and avian nest parasites and developed a theoretical model to evaluate the conditions under which mobs arise. We presented taxidermied mounts of predators on adult birds (hawks and owls) and of nest threats (crows and cuckoos) at different distances to nests of Phylloscopus warblers. Even when alone, birds are aggressive toward predators of adult birds, both at and away from their nests. By contrast, birds aggressively confront nest threats alone only when they have a nest nearby. However, strong initial responses by nest owners lead individuals without nearby nests to increase their responses, thereby generating a mob. Building on these findings, we derive the conditions in which individuals are incentivized to invest more when joining a high-gain individual compared to when acting alone. Strong responses of high-gain individuals acting alone tend to reduce the investments of other high-gain individuals that subsequently join. However, individuals that benefit sufficiently little from acting alone increase their investments when joining a high-gain individual and can even be sufficiently incentivized to join in when they would otherwise not act alone. Together, these results suggest an important role for key individuals in the generation of some group behaviors.}, } @article {pmid30205026, year = {2018}, author = {Costa-Pereira, R and Araújo, MS and Olivier, RDS and Souza, FL and Rudolf, VHW}, title = {Prey Limitation Drives Variation in Allometric Scaling of Predator-Prey Interactions.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {E139-E149}, doi = {10.1086/698726}, pmid = {30205026}, issn = {1537-5323}, abstract = {Ecologists have long searched for a universal size-scaling constant that governs trophic interactions. Although this is an appealing theoretical concept, predator-prey size ratios (PPSRs) vary strikingly across and within natural food webs, meaning that predators deviate from their optimal prey size by consuming relatively larger or smaller prey. Here we suggest that this unexpected variation in allometric scaling of trophic interactions can be predicted by gradients of prey limitation consistent with predictions from optimal foraging theory. We analyzed >6,000 trophic interactions of 52 populations from four tropical frog species along a gradient of prey limitation. The mean of PPSR and its variance differed up to two orders of magnitude across and within food webs. Importantly, as prey availability decreased across food webs, PPSR and its variance became more size dependent. Thus, trophic interactions did not follow a fixed allometric scaling but changed predictably with the strength of prey limitation. Our results emphasize the importance of ecological contexts in arranging food webs and the need to incorporate ecological drivers of PPSR and its variance in food web and community models.}, } @article {pmid30205025, year = {2018}, author = {Arbuthnott, D}, title = {Female Life-History Trade-Offs and the Maintenance of Genetic Variation in Drosophila melanogaster.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {448-460}, doi = {10.1086/698727}, pmid = {30205025}, issn = {1537-5323}, abstract = {Why do we observe substantial variation in fitness-related traits under strong natural or sexual selection? While there is support for several selective and neutral mechanisms acting in select systems, we lack a comprehensive analysis of the relative importance of various mechanisms within a single system. Furthermore, while sexually selected male traits have been a central focus of this paradox, female sexual traits have rarely been considered. In this study, I evaluate the contribution of various selective mechanisms to the maintenance of substantial variation in female attractiveness and offspring production observed among Drosophila melanogaster genotypes. I tested for contributions from antagonistic pleiotropy, frequency-dependent selection, changing environments, and sexual conflict. I found negative genetic correlations between some traits (male attractiveness vs. female resistance to male harm, early-life offspring production vs. reproductive senescence) and genotype-specific changes in fitness between environments. However, no measurement found strong trade-offs among the fitness components of these genotypes. Overall, I find little evidence that any one mechanism is strong enough to maintain genetic variation on its own. Instead, I suggest that many mechanisms may weaken the selection among genotypes, which would collectively allow neutral processes such as mutation-selection balance to maintain genetic variation within populations.}, } @article {pmid30205024, year = {2018}, author = {Naya, DE and Naya, H and White, CR}, title = {On the Interplay among Ambient Temperature, Basal Metabolic Rate, and Body Mass.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {518-524}, doi = {10.1086/698372}, pmid = {30205024}, issn = {1537-5323}, abstract = {One of the most generalized conclusions arising from studies analyzing the ecological variation of energy metabolism in endotherms is the apparent negative correlation between ambient temperature and mass-independent basal metabolic rate (residual BMR). As a consequence, ambient temperature has been considered the most important external factor driving the evolution of residual BMR. It is not clear, however, whether this relationship is size dependent, and artifacts such as the biased sampling of body masses in physiological data sets could cause us to overstate the ubiquity of the relationship. Accordingly, here we used published data on body mass (mb), BMR, and annual mean temperature (Tmean) for 458 mammal species (and/or subspecies) to examine the size dependence of the relationship between temperature and BMR. We found a significant interaction between mb and Tmean as predictors of residual BMR, such that the effect of Tmean on residual BMR decreases as a function of mb. In line with this, the amount of residual variance in BMR explained by Tmean decreased with increasing mb, from 20%-30% at body sizes of less than 100 g to almost 0 at body sizes greater than 1,000 g. These data suggest that our current understanding of the importance of broad-scale variation in ambient temperature as a driver of metabolic evolution in endotherms probably is affected by the large number of small species in both nature and physiological data sets.}, } @article {pmid30205023, year = {2018}, author = {Blackwood, JC and Machta, J and Meyer, AD and Noble, AE and Hastings, A and Liebhold, AM}, title = {Competition and Stragglers as Mediators of Developmental Synchrony in Periodical Cicadas.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {479-489}, doi = {10.1086/699255}, pmid = {30205023}, issn = {1537-5323}, abstract = {Periodical cicadas are enigmatic organisms: broods spanning large spatial ranges consist of developmentally synchronized populations of 3-4 sympatric species that emerge as adults every 13 or 17 years. Only one brood typically occupies any single location, with well-defined boundaries separating distinct broods. The cause of such synchronous development remains uncertain, but it is known that synchronous emergence of large numbers of adults in a single year satiates predators, allowing a substantial fraction of emerging adults to survive long enough to reproduce. Competition among nymphs feeding on tree roots almost certainly plays a role in limiting populations. However, due to the difficulty of working with such long-lived subterranean life stages, the mechanisms governing competition in periodical cicadas have not been identified. A second process that may affect synchrony among periodical cicadas is their ability to delay or accelerate their emergence as adults by 1 year and accelerate it by 4 years (stragglers). We develop a nonlinear Leslie matrix-type model that describes cicada dynamics accounting for predation, competition, and stragglers. Using numerical simulations, we identify conditions that generate dynamics in which a single brood occupies a given geographical location. Our results show that while stragglers have the potential for introducing multiple sympatric broods, the interaction of interbrood competition with predation-driven Allee effects creates a system resistant to such invasions, and populations maintain developmental synchrony.}, } @article {pmid30205022, year = {2018}, author = {Schenk, JJ and Steppan, SJ}, title = {The Role of Geography in Adaptive Radiation.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {415-431}, doi = {10.1086/699221}, pmid = {30205022}, issn = {1537-5323}, abstract = {Although the importance of biogeography in the speciation process is well recognized, the fundamental role of geographic diversification during adaptive radiations has not been studied to determine its importance during the adaptive radiation process. We examined the relationship between lineage and regional diversification patterns in the South American rodent subfamily Sigmodontinae, one of the best candidates for an adaptive radiation in mammals, to propose a conceptual framework for geographic transitions during adaptive radiations. We reconstructed a time-calibrated phylogeny from four nuclear genes and one mitochondrial gene for 77% of sigmodontine diversity. Historical biogeography was reconstructed among 14 regions, for which we applied a sliding-window approach to estimate regional transition rates through time. We compared these rate patterns and measured whether regions consisted of species that were more phylogenetically related than expected by chance. Following the initial South American colonization around 7 million years ago, multiple expansions from northern regions correlated with a burst of speciation. Subsequently, both diversification and regional transition rates decreased overall and within the majority of regions. Despite high regional transition rates, nearly all regional assemblages were phylogenetically clustered, indicating that within-region diversification was common. We conclude that biogeographic complexity and partitioning played a profound role in the adaptive radiation of the South American Sigmodontinae (Oryzomyalia), the degree to which is determined by the relative scales of spatial variation and dispersal abilities.}, } @article {pmid30205021, year = {2018}, author = {Rudin-Bitterli, TS and Mitchell, NJ and Evans, JP}, title = {Environmental Stress Increases the Magnitude of Nonadditive Genetic Variation in Offspring Fitness in the Frog Crinia georgiana.}, journal = {The American naturalist}, volume = {192}, number = {4}, pages = {461-478}, doi = {10.1086/699231}, pmid = {30205021}, issn = {1537-5323}, abstract = {When organisms encounter heterogeneous environments, selection may favor the ability of individuals to tailor their phenotypes to suit the prevailing conditions. Understanding the genetic basis of plastic responses is therefore vital for predicting whether susceptible populations can adapt and persist under new selection pressures. Here, we investigated whether there is potential for adaptive plasticity in development time in the quacking frog Crinia georgiana, a species experiencing a drying climate. Using a North Carolina II breeding design, we exposed 90 family groups to two water depth treatments (baseline and low water) late in larval development. We then estimated the contribution of additive and nonadditive sources of genetic variation to early offspring fitness under both environments. Our results revealed a marked decline in larval fitness under the stressful (low water) rearing environment but also that additive genetic variation was negligible for all traits. However, in most cases, we found significant sire-by-dam interactions, indicating the importance of nonadditive genetic variation for offspring fitness. Moreover, sire-by-dam interactions were modified by the treatment, indicating that patterns of nonadditive genetic variance depend on environmental context. For all traits, we found higher levels of nonadditive genetic variation (relative to total phenotypic variation) when larvae were reared under stressful conditions, suggesting that the fitness costs associated with incompatible parental crosses (e.g., homozygous deleterious recessive alleles) will only be expressed when water availability is low. Taken together, our results highlight the need to consider patterns of nonadditive genetic variation under contrasting selective regimes when considering the resilience of species to environmental change.}, } @article {pmid30204906, year = {2018}, author = {Filowitz, GL and Rajakumar, R and O'Shaughnessy, KL and Cohn, MJ}, title = {Cartilaginous Fishes Provide Insights into the Origin, Diversification, and Sexually Dimorphic Expression of Vertebrate Estrogen Receptor Genes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2695-2701}, doi = {10.1093/molbev/msy165}, pmid = {30204906}, issn = {1537-1719}, abstract = {Vertebrate estrogen receptors (ERs) perform numerous cell signaling and transcriptional regulatory functions. ERɑ (Esr1) and ERβ (Esr2) likely evolved from an ancestral receptor that duplicated and diverged at the protein and cis-regulatory levels, but the evolutionary history of ERs, including the timing of proposed duplications, remains unresolved. Here we report on identification of two distinct ERs in cartilaginous fishes and demonstrate their orthology to ERα and ERβ. Phylogenetic analyses place the ERα/ERβ duplication near the base of crown gnathostomes (jawed vertebrates). We find that ERα and ERβ from little skate (Leucoraja erinacea) and mammals share key subtype-specific residues, indicating conserved protein evolution. In contrast, jawless fishes have multiple non-orthologous Esr genes that arose by parallel duplications. Esr1 and Esr2 are expressed in subtype-specific and sexually dimorphic patterns in skate embryos, suggesting that ERs might have functioned in sexually dimorphic development before the divergence of cartilaginous and bony fishes.}, } @article {pmid30204860, year = {2018}, author = {Mafessoni, F and Prasad, RB and Groop, L and Hansson, O and Prüfer, K}, title = {Turning Vice into Virtue: Using Batch-Effects to Detect Errors in Large Genomic Data Sets.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2697-2708}, pmid = {30204860}, issn = {1759-6653}, abstract = {It is often unavoidable to combine data from different sequencing centers or sequencing platforms when compiling data sets with a large number of individuals. However, the different data are likely to contain specific systematic errors that will appear as SNPs. Here, we devise a method to detect systematic errors in combined data sets. To measure quality differences between individual genomes, we study pairs of variants that reside on different chromosomes and co-occur in individuals. The abundance of these pairs of variants in different genomes is then used to detect systematic errors due to batch effects. Applying our method to the 1000 Genomes data set, we find that coding regions are enriched for errors, where ∼1% of the higher frequency variants are predicted to be erroneous, whereas errors outside of coding regions are much rarer (<0.001%). As expected, predicted errors are found less often than other variants in a data set that was generated with a different sequencing technology, indicating that many of the candidates are indeed errors. However, predicted 1000 Genomes errors are also found in other large data sets; our observation is thus not specific to the 1000 Genomes data set. Our results show that batch effects can be turned into a virtue by using the resulting variation in large scale data sets to detect systematic errors.}, } @article {pmid30204586, year = {2018}, author = {Brown-Elliott, BA and Simmer, PJ and Trovato, A and Hyle, EP and Droz, S and Buckwalter, SP and Borroni, E and Branda, JA and Iana, E and Mariottini, A and Nelson, J and Matteelli, A and Toney, NC and Scarparo, C and de Man, TJB and Vasireddy, R and Gandhi, RT and Wengenack, NL and Cirillo, DM and Wallace, RJ and Tortoli, E}, title = {Mycobacterium decipiens sp. nov., a new species closely related to the Mycobacterium tuberculosis complex.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3557-3562}, doi = {10.1099/ijsem.0.003031}, pmid = {30204586}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Humans ; Italy ; Mycobacterium/*classification/genetics/isolation & purification ; Mycobacterium Infections/*microbiology ; Mycobacterium tuberculosis ; Mycolic Acids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tuberculosis, Cutaneous/*microbiology ; United States ; }, abstract = {Two mycobacterial strains with close similarity to the Mycobacterium tuberculosis complex (MTBC) were isolated from cutaneous lesions of patients in the USA and Italy. At the phenotypic level, similarities to the MTBC included slow growth rate, rough morphotype of the unpigmented colonies and nearly identical high-performance liquid chromatography profiles of mycolic acids. In contrast to the MTBC, the strains were niacin- and nitrate-negative, and catalase-positive both at 68 °C and in semi-quantitative tests. The clinical isolates were more closely related to M. tuberculosis than to any other known mycobacterium and scored positive with commercial DNA probes (Hologic AccuProbe M. tuberculosis). Both average nucleotide identity and genome-to-genome distance suggested the strains are different from the MTBC. Therefore, given the distinguishing phenotypic and genomic-scale differences, we submit that the strains belong to a new species we have named Mycobacteriumdecipiens with type strain TBL 1200985T (=ATCC TSD-117T=DSM 105360T).}, } @article {pmid30204585, year = {2018}, author = {Fan, QM and Zhang, RG and Chen, HY and Feng, QQ and Lv, J}, title = {Sphingomonas floccifaciens sp. nov., isolated from subterranean sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002983}, pmid = {30204585}, issn = {1466-5034}, abstract = {A Gram-stain-negative, non-motile, non-sporulating, rod-shaped, orange-pigmented bacterium, designated strain FQM01T, was isolated from a subterranean sediment sample in the Mohe permafrost area, China. Strain FQM01T grew optimally at 25 °C, pH 7.0 and NaCl concentration of 0 % (w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain FQM01T belonged to the genus Sphingomonas. The closest phylogenetic relative was Sphingomonas spermidinifaciens GDMCC 1.657T (97.6 %), followed by Sphingomonas mucosissima DSM 17494T (97.2 %). The DNA G+C content of the isolate was 66.9 mol%. Strain FQM01T contained Q-10 as the predominant ubiquinone, and C18 : 1ω6c and/or C18 : 1ω7c, C16 : 1ω6c and/or C16 : 1ω7c, C16 : 0, C14 : 0 2-OH and C18 : 1ω7c 11 methyl as the major fatty acids. Major polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, sphingoglycolipid and an unidentified glycolipid. Only sym-homospermidine was detected as the polyamine. On the basis of phylogenetic and phenotypic data, strain FQM01T is considered to represent a novel species of Sphingomonas for which the name Sphingomonasfloccifaciens sp. nov. is proposed. The type strain is FQM01T (=CGMCC 1.15797T=KCTC 52630T).}, } @article {pmid30204584, year = {2018}, author = {Kiran, S and Schumann, P and Busse, HJ and Spröer, C and Rana, A and Pal, M and Korpole, S and Tewari, R and Gulati, A}, title = {Psychromicrobium lacuslunae sp. nov., isolated from a high altitude lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3416-3423}, doi = {10.1099/ijsem.0.002997}, pmid = {30204584}, issn = {1466-5034}, mesh = {*Altitude ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; India ; Lakes/*microbiology ; Micrococcaceae/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; *Water Microbiology ; }, abstract = {The novel strain IHBB 11108T was a psychrotolerant and alkaliphilic bacterium isolated from the subsurface water of Chandra Tal Lake in the Lahaul-Spiti valley located in the Indian trans-Himalayas. Cells were Gram-stain-positive, aerobic, non-motile, catalase-positive and oxidase-negative. The strain grew at 5-37 °C (optimum 28 °C), pH 5.0-12.0 (optimum pH 7.0) and with up to 8 % NaCl (optimum 1 %). The 16S rRNA gene sequence analysis revealed the highest relatedness of strain IHBB 11108T with Psychromicrobium silvestre DSM 102047T (97.5 %), Arthrobacter russicus DSM 14555T (97.4 %) and Renibacterium salmoninarum ATCC 33209T (97.4 %). The strain contained a quinone system with 57.2 % MK-9(H2), 39.1 % MK-10(H2), 3.0 % MK-8(H2) and 0.7 % MK-7(H2). The polar lipids detected were diphosphatidylglycerol, dimannosylglyceride, phosphatidylinositol, phosphatidylglycerol, monogalactosyldiacylglycerol, one unidentified glycolipid and four unidentified lipids. The cell-wall peptidoglycan structure type was A3α l-Lys-l-Thr-l-Ala with substitution of the α-carboxyl group of d-Glu by alanine amide. Anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0 were the predominant fatty acids. The genomic DNA G+C content was 59.0 mol%. The DNA-DNA relatedness of strain IHBB 11108T was 46.7±2.2, 43.1±2.5 and 19.1±2.4 % with P. silvestre DSM 102047T, A. russicus DSM 14555T and R. salmoninarum ATCC 33209T, respectively. On the basis of the results of the phenotypic, chemotaxonomic and phylogenetic analyses, IHBB 11108T is considered to represent a novel species of the genus Psychromicrobium for which the name Psychromicrobium lacuslunae sp. nov. is proposed. The type strain is IHBB 11108T (=MTCC 12460T=MCC 2780T=JCM 31143T=KACC 19070T).}, } @article {pmid30204583, year = {2018}, author = {Murray, AK and Lee, J and Bendall, R and Zhang, L and Sunde, M and Schau Slettemeås, J and Gaze, W and Page, AJ and Vos, M}, title = {Staphylococcus cornubiensis sp. nov., a member of the Staphylococcus intermedius Group (SIG).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3404-3408}, doi = {10.1099/ijsem.0.002992}, pmid = {30204583}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Cellulitis/microbiology ; DNA, Bacterial/genetics ; Genes, Bacterial ; Humans ; Male ; Middle Aged ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin Diseases, Bacterial/*microbiology ; Staphylococcal Infections/*microbiology ; Staphylococcus/*classification/genetics/isolation & purification ; Staphylococcus intermedius ; United Kingdom ; }, abstract = {We here describe a novel species in the Staphylococcus intermedius Group (SIG) which is phenotypically similar to Staphylococcus pseudintermedius but is genomically distinct from it and other SIG members, with an average nucleotide identity of 90.2 % with its closest relative S. intermedius. The description of Staphylococcus cornubiensis sp. nov. is based on strain NW1T (=NCTC 13950T=DSM 105366T) isolated from a human skin infection in Cornwall, UK. Although pathogenic, NW1T carries no known virulence genes or mobilizable antibiotic resistance genes and further studies are required to assess the prevalence of this species in humans as well as its potential presence in companion animals.}, } @article {pmid30204582, year = {2018}, author = {Zhou, S and Ren, Q and Li, Y and Liu, J and Wang, X and Wu, Y and Zhang, Y and Zhang, XH}, title = {Abyssibacter profundi gen. nov., sp. nov., a marine bacterium isolated from seawater of the Mariana Trench.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {11}, pages = {3424-3429}, doi = {10.1099/ijsem.0.002999}, pmid = {30204582}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Pacific Ocean ; Phosphatidylethanolamines/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Water Microbiology ; }, abstract = {A Gram-stain-negative, strictly aerobic, short-rod-shaped bacterium, motile by a single polar flagellum, designated OUC007T, was isolated from seawater at a depth of 1000 m in the Mariana Trench. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain OUC007T formed a lineage within the family Salinisphaeraceae that was distinct from the most closely related genera Oceanococcus and Salinisphaera, with 16S rRNA gene sequences similarities ranging from 89.3 to 90.8 %, respectively. Strain OUC007T grew with 0-7 % (w/v) NaCl (optimum, 2-3 %), at 10-45 °C (37 °C) and at pH 7.0-9.0 (7.0-8.0). The major respiratory quinone was ubiquinone-8 (Q-8). The polar lipids of strain OUC007T comprised one phosphatidylethanolamine and three unidentified polar lipids. The predominant fatty acid (more than 10 % of total fatty acids) was summed feature 8 (C18 : 1ω7c or/and C18 : 1ω6c). The DNA G+C content of strain OUC007T was 63.1 mol%. On the basis of polyphasic taxonomic analysis, the strain OUC007T is considered to represent a novel species in a new genus of the family Salinisphaeraceae, for which the name Abyssibacter profundi gen. nov., sp. nov. is proposed. The type strain is OUC007T (=KCTC 52933T=MCCC 1K03450T).}, } @article {pmid30203410, year = {2018}, author = {Juntunen, HL and Leinen, LJ and Pitts, BK and O'Hanlon, SM and Theiling, BP and Barge, LM and Videau, P and Gaylor, MO}, title = {Investigating the Kinetics of Montmorillonite Clay-Catalyzed Conversion of Anthracene to 9,10-Anthraquinone in the Context of Prebiotic Chemistry.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {3}, pages = {321-330}, pmid = {30203410}, issn = {1573-0875}, support = {College of Arts and Sciences faculty Research Grant//Dakota State University (US)/ ; DSU Student Research Initiative Research Grant//Dakota State University (US)/ ; }, mesh = {Anthracenes/*chemistry ; Anthraquinones/*chemistry ; Bentonite/*chemistry ; Catalysis ; Chemistry, Inorganic ; Clay/chemistry ; Kinetics ; Origin of Life ; Polycyclic Aromatic Hydrocarbons/*chemistry ; Temperature ; }, abstract = {Carbonaceous meteorites contributed polycyclic aromatic hydrocarbons (PAHs) to the organic inventory of the primordial Earth where they may have reacted on catalytic clay mineral surfaces to produce quinones capable of functioning as redox species in emergent biomolecular systems. To address the feasibility of this hypothesis, we assessed the kinetics of anthracene (1) conversion to 9,10-anthraquinone (2) in the presence of montmorillonite clay (MONT) over the temperature range 25 to 250 °C. Apparent rates of conversion were concentration independent and displayed a sigmoidal relationship with temperature, and conversion efficiencies ranged from 0.027 to 0.066%. Conversion was not detectable in the absence of MONT or a sufficiently high oxidation potential (in this case, molecular oxygen (O2)). These results suggest a scenario in which meteoritic 1 and MONT interactions could yield biologically important quinones in prebiotic planetary environments.}, } @article {pmid30203409, year = {2018}, author = {Li, Z and Lyu, R and Tower, J}, title = {Models of Replicator Proliferation Involving Differential Replicator Subunit Stability.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {3}, pages = {331-342}, pmid = {30203409}, issn = {1573-0875}, support = {R01 AG057741/AG/NIA NIH HHS/United States ; R56 AG049629/AG/NIA NIH HHS/United States ; R56AG049629//National Institute on Aging/ ; R01AG057741//National Institute on Aging/ ; }, mesh = {DNA/genetics ; DNA Replication/*genetics ; *Evolution, Molecular ; *Models, Biological ; *Origin of Life ; RNA/genetics ; }, abstract = {Several models for the origin of life involve molecules that are capable of self-replication, such as self-replicating polymers composed of RNA or DNA or amino acids. Here we consider a hypothetical replicator (AB) composed of two subunits, A and B. Programs written in Python and C programming languages were used to model AB replicator abundance as a function of cycles of replication (iterations), under specified hypothetical conditions. Two non-exclusive models describe how a reduced stability for B relative to A can have an advantage for replicator activity and/or evolution by generating free A subunits. In model 1, free A subunits associate with AB replicators to create AAB replicators with greater activity. In simulations, reduced stability of B was beneficial when the replication activity of AAB was greater than two times the replication activity of AB. In model 2, the free A subunit is inactive for some number of iterations before it re-creates the B subunit. A re-creates the B subunit with an equal chance of creating B or B', where B' is a mutant that increases AB' replicator activity relative to AB. In simulations, at moderate number of iterations (< 15), a shorter survival time for B is beneficial when the stability of B is greater than the inactive time of A. The results are consistent with the hypothesis that reduced stability for a replicator subunit can be advantageous under appropriate conditions.}, } @article {pmid30203337, year = {2018}, author = {Bizarria, R and Moia, IC and Montoya, QV and Polezel, DA and Rodrigues, A}, title = {Soluble Compounds of Filamentous Fungi Harm the Symbiotic Fungus of Leafcutter Ants.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1602-1608}, pmid = {30203337}, issn = {1432-0991}, support = {2011/16765-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 478559/2011-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)/ ; }, mesh = {Animals ; Ants/*microbiology ; Fungi/*physiology ; Symbiosis/*physiology ; }, abstract = {Chemical compounds are key to understand symbiotic interactions. In the leafcutter ant-microbe symbiosis a plethora of filamentous fungi continuously gain access the ant colonies through plant substrate collected by workers. Many filamentous fungi are considered transient in attine ant colonies, however, their real ecological role in this environment still remains unclear. A possible role of these microorganisms is the antagonism towards Leucoagaricus gongylophorus, the mutualistic fungus that serve as food for several leafcutter ant species. Here, we showed the antagonism of filamentous fungi isolated from different sources, and the negative impacts of their metabolites on the growth of the ant-fungal cultivar. Our results demonstrate that the chemical compounds produced by filamentous fungi can harm the mutualistic fungus of leafcutter ants.}, } @article {pmid30203090, year = {2018}, author = {Gillis, A and Fayad, N and Makart, L and Bolotin, A and Sorokin, A and Kallassy, M and Mahillon, J}, title = {Role of plasmid plasticity and mobile genetic elements in the entomopathogen Bacillus thuringiensis serovar israelensis.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {6}, pages = {829-856}, pmid = {30203090}, issn = {1574-6976}, mesh = {Animals ; Bacillus thuringiensis/*genetics/pathogenicity ; Genetic Variation ; Insecta/microbiology ; Interspersed Repetitive Sequences/*genetics ; Larva/microbiology ; Plasmids/*genetics ; Species Specificity ; }, abstract = {Bacillus thuringiensis is a well-known biopesticide that has been used for more than 80 years. This spore-forming bacterium belongs to the group of Bacillus cereus that also includes, among others, emetic and diarrheic pathotypes of B. cereus, the animal pathogen Bacillus anthracis and the psychrotolerant Bacillus weihenstephanensis. Bacillus thuringiensis is rather unique since it has adapted its lifestyle as an efficient pathogen of specific insect larvae. One of the peculiarities of B. thuringiensis strains is the extent of their extrachromosomal pool, with strains harbouring more than 10 distinct plasmid molecules. Among the numerous serovars of B. thuringiensis, 'israelensis' is certainly emblematic since its host spectrum is apparently restricted to dipteran insects like mosquitoes and black flies, vectors of human and animal diseases such as malaria, yellow fever, or river blindness. In this review, the putative role of the mobile gene pool of B. thuringiensis serovar israelensis in its pathogenicity and dedicated lifestyle is reviewed, with specific emphasis on the nature, diversity, and potential mobility of its constituents. Variations among the few related strains of B. thuringiensis serovar israelensis will also be reported and discussed in the scope of this specialised insect pathogen, whose lifestyle in the environment remains largely unknown.}, } @article {pmid30203072, year = {2018}, author = {Graells, T and Ishak, H and Larsson, M and Guy, L}, title = {The all-intracellular order Legionellales is unexpectedly diverse, globally distributed and lowly abundant.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsle/fiy185}, pmid = {30203072}, issn = {1574-6941}, abstract = {Legionellales is an order of the Gammaproteobacteria, only composed of host-adapted, intracellular bacteria, including the accidental human pathogens Legionella pneumophila and Coxiella burnetii. Although the diversity in terms of lifestyle is large across the order, only a few genera have been sequenced, owing to the difficulty to grow intracellular bacteria in pure culture. In particular, we know little about their global distribution and abundance.Here, we analyze 16/18S rDNA amplicons both from tens of thousands of published studies and from two separate sampling campaigns in and around ponds and in a silver mine. We demonstrate that the diversity of the order is much larger than previously thought, with over 450 uncultured genera. We show that Legionellales are found in about half of the samples from freshwater, soil and marine environments, and quasi-ubiquitous in man-made environments. Their abundance is low, typically 0.1%, with few samples up to 1%. Most Legionellales OTUs are globally distributed, while many do not belong to a previously identified species.This study sheds a new light on the ubiquity and diversity of one major group of host-adapted bacteria. It also emphasizes the need to use metagenomics to better understand the role of host-adapted bacteria in all environments.}, } @article {pmid30203071, year = {2018}, author = {Raimundo, J and Sobral, R and Laranjeira, S and Costa, MMR}, title = {Successive Domain Rearrangements Underlie the Evolution of a Regulatory Module Controlled by a Small Interfering Peptide.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2873-2885}, pmid = {30203071}, issn = {1537-1719}, abstract = {The establishment of new interactions between transcriptional regulators increases the regulatory diversity that drives phenotypic novelty. To understand how such interactions evolve, we have studied a regulatory module (DDR) composed by three MYB-like proteins: DIVARICATA (DIV), RADIALIS (RAD), and DIV-and-RAD-Interacting Factor (DRIF). The DIV and DRIF proteins form a transcriptional complex that is disrupted in the presence of RAD, a small interfering peptide, due to the formation of RAD-DRIF dimers. This dynamic interaction result in a molecular switch mechanism responsible for the control of distinct developmental processes in plants. Here, we have determined how the DDR regulatory module was established by analyzing the origin and evolution of the DIV, DRIF, and RAD protein families and the evolutionary history of their interactions. We show that duplications of a pre-existing MYB domain originated the DIV and DRIF protein families in the ancestral lineage of green algae, and, later, the RAD family in seed plants. Intraspecies interactions between the MYB domains of DIV and DRIF proteins are detected in green algae, whereas the earliest evidence of an interaction between DRIF and RAD proteins occurs in the gymnosperms, coincident with the establishment of the RAD family. Therefore, the DDR module evolved in a stepwise progression with the DIV-DRIF transcription complex evolving prior to the antagonistic RAD-DRIF interaction that established the molecular switch mechanism. Our results suggest that the successive rearrangement and divergence of a single protein domain can be an effective evolutionary mechanism driving new protein interactions and the establishment of novel regulatory modules.}, } @article {pmid30203066, year = {2018}, author = {Corinne, BP and Najwa, T and Hélène, G and Corentin, H and Didier, D}, title = {New insights into the pelagic microorganisms involved in the methane cycle in the meromictic Lake Pavin through metagenomics.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy183}, pmid = {30203066}, issn = {1574-6941}, abstract = {Advances in metagenomics have given rise to the possibility of obtaining genome sequences from uncultured microorganisms, even for those poorly represented in microbial community, thereby providing important means to study their ecology and evolution. In this study, metagenomic sequencing was carried out at four sampling depths having different oxygen concentrations or environmental conditions in the water column of Lake Pavin. By analyzing the sequenced reads and matching the contigs to the proxy genomes of the closest cultivated relatives, we evaluated the metabolic potential of the dominant planktonic species involved in the methane cycle. We demonstrated that methane-producing communities were dominated by the genus Methanoregula while methane-consuming communities were dominated by the genus Methylobacter, thus confirming prior observations. Our work allowed the reconstruction of a draft of their core metabolic pathways. Although hydrogenotrophs, the presence of the genes required for acetate activation in the methanogen genome were also detected. Regarding methanotrophy, Methylobacter was present in the same areas as the non-methanotrophic, methylotrophic Methylotenera, which could suggest a relationship between these two groups. Furthermore, the presence of a large gene inventory for nitrogen metabolism (nitrate transport, denitrification, nitrite assimilation and nitrogen fixation, for instance) was detected in the Methylobacter genome.}, } @article {pmid30203003, year = {2018}, author = {Laurin-Lemay, S and Rodrigue, N and Lartillot, N and Philippe, H}, title = {Conditional Approximate Bayesian Computation: A New Approach for Across-Site Dependency in High-Dimensional Mutation-Selection Models.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2819-2834}, doi = {10.1093/molbev/msy173}, pmid = {30203003}, issn = {1537-1719}, abstract = {A key question in molecular evolutionary biology concerns the relative roles of mutation and selection in shaping genomic data. Moreover, features of mutation and selection are heterogeneous along the genome and over time. Mechanistic codon substitution models based on the mutation-selection framework are promising approaches to separating these effects. In practice, however, several complications arise, since accounting for such heterogeneities often implies handling models of high dimensionality (e.g., amino acid preferences), or leads to across-site dependence (e.g., CpG hypermutability), making the likelihood function intractable. Approximate Bayesian Computation (ABC) could address this latter issue. Here, we propose a new approach, named Conditional ABC (CABC), which combines the sampling efficiency of MCMC and the flexibility of ABC. To illustrate the potential of the CABC approach, we apply it to the study of mammalian CpG hypermutability based on a new mutation-level parameter implying dependence across adjacent sites, combined with site-specific purifying selection on amino-acids captured by a Dirichlet process. Our proof-of-concept of the CABC methodology opens new modeling perspectives. Our application of the method reveals a high level of heterogeneity of CpG hypermutability across loci and mild heterogeneity across taxonomic groups; and finally, we show that CpG hypermutability is an important evolutionary factor in rendering relative synonymous codon usage. All source code is available as a GitHub repository (https://github.com/Simonll/LikelihoodFreePhylogenetics.git).}, } @article {pmid30202983, year = {2018}, author = {Sharir-Ivry, A and Xia, Y}, title = {Nature of Long-Range Evolutionary Constraint in Enzymes: Insights from Comparison to Pseudoenzymes with Similar Structures.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2597-2606}, doi = {10.1093/molbev/msy177}, pmid = {30202983}, issn = {1537-1719}, abstract = {Enzymes are known to fine-tune their sequences to optimize catalytic function, yet quantitative evolutionary design principles of enzymes remain elusive on the proteomic scale. Recently, it was found that the catalytic site in enzymes induces long-range evolutionary constraint, where even sites distant to the catalytic site are more conserved than expected. Given that protein-fold usage is generally different between enzymes and nonenzymes, it remains an open question to what extent this long-range evolutionary constraint in enzymes is dictated, either directly or indirectly, by the special three-dimensional structure of the enzyme. To investigate this question, we have compared evolutionary properties of enzymes with those of counterpart pseudoenzymes that share the same protein fold but are catalytically inactive. We found that the long-range evolutionary constraint observed in enzymes is significantly reduced in pseudoenzyme counterparts, despite very high structural similarity (∼1.5 Å RMSD on average). Furthermore, this significant reduction in long-range evolutionary constraint is observed even in pseudoenzyme counterparts which retain the ligand-binding ability of enzymes. Finally, the distance between the site that induces the highest gradient of sequence conservation and the pseudocatalytic site in pseudoenzymes is significantly larger than the corresponding distance in enzymes. Taken together, our results suggest that the long-range evolutionary constraint in enzymes is induced mainly by the presence of the catalytic site rather than by the special three-dimensional structure of the enzyme, and that such long-range evolutionary constraint in enzymes depends mainly on the catalytic function of the active site rather than on the ligand-binding ability of the enzyme.}, } @article {pmid30202970, year = {2018}, author = {Taylor-Brown, A and Pillonel, T and Greub, G and Vaughan, L and Nowak, B and Polkinghorne, A}, title = {Metagenomic Analysis of Fish-Associated Ca. Parilichlamydiaceae Reveals Striking Metabolic Similarities to the Terrestrial Chlamydiaceae.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2587-2595}, pmid = {30202970}, issn = {1759-6653}, abstract = {Chlamydiae are an example of obligate intracellular bacteria that possess highly reduced, compact genomes (1.0-3.5 Mbp), reflective of their abilities to sequester many essential nutrients from the host that they no longer need to synthesize themselves. The Chlamydiae is a phylum with a very wide host range spanning mammals, birds, fish, invertebrates, and unicellular protists. This ecological and phylogenetic diversity offers ongoing opportunities to study intracellular survival and metabolic pathways and adaptations. Of particular evolutionary significance are Chlamydiae from the recently proposed Ca. Parilichlamydiaceae, the earliest diverging clade in this phylum, species of which are found only in aquatic vertebrates. Gill extracts from three Chlamydiales-positive Australian aquaculture species (Yellowtail kingfish, Striped trumpeter, and Barramundi) were subject to DNA preparation to deplete host DNA and enrich microbial DNA, prior to metagenome sequencing. We assembled chlamydial genomes corresponding to three Ca. Parilichlamydiaceae species from gill metagenomes, and conducted functional genomics comparisons with diverse members of the phylum. This revealed highly reduced genomes more similar in size to the terrestrial Chlamydiaceae, standing in contrast to members of the Chlamydiae with a demonstrated cosmopolitan host range. We describe a reduction in genes encoding synthesis of nucleotides and amino acids, among other nutrients, and an enrichment of predicted transport proteins. Ca. Parilichlamydiaceae share 342 orthologs with other chlamydial families. We hypothesize that the genome reduction exhibited by Ca. Parilichlamydiaceae and Chlamydiaceae is an example of within-phylum convergent evolution. The factors driving these events remain to be elucidated.}, } @article {pmid30202963, year = {2018}, author = {Chiellini, C and Miceli, E and Bacci, G and Fagorzi, C and Coppini, E and Fibbi, D and Bianconi, G and Mengoni, A and Canganella, F and Fani, R}, title = {Spatial structuring of bacterial communities in epilithic biofilms in the Acquarossa river (Italy).}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy181}, pmid = {30202963}, issn = {1574-6941}, abstract = {Epilithic river biofilms characterize the rock surfaces along the Acquarossa river (Viterbo, Italy); they are in part red and in part black colored, maintaining a well-defined borderline. This peculiarity has raised questions about the biotic and abiotic phenomena that might avoid the mixing of the two biofilms. In this study, the structuring of bacterial communities in black and red epilithic biofilm in the Acquarossa river has been investigated with both culture dependent and independent approaches. Data obtained highlighted a (very) different taxonomic composition of black and red epilithons bacterial communities, dominated by Acinetobacter sp. and iron-oxidizing bacteria, respectively. The chemical characterization of both river water and biofilms revealed a substantial heavy metals pollution of the environment; heavy metals were also differentially accumulated in red and black epilithons. Overall, our data revealed that the structuring of red and black epilithons might be affected mainly by the antagonistic interactions exhibited by bacterial genera dominating the two biofilms. These findings suggest that biotic factors might be responsible for the structuring of natural bacterial communities, suggesting that there is a selection of populations at very small scale, and that different populations might compete for different niches.}, } @article {pmid30202961, year = {2018}, author = {Kohl, KD and Oakeson, KF and Orr, TJ and Miller, AW and Forbey, JS and Phillips, CD and Dale, C and Weiss, RB and Dearing, MD}, title = {Metagenomic sequencing provides insights into microbial detoxification in the guts of small mammalian herbivores (Neotoma spp.).}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy184}, pmid = {30202961}, issn = {1574-6941}, abstract = {Microbial detoxification of plant toxins influences the use of plants as food sources by herbivores. Stephen's woodrats (Neotoma stephensi) specialize on juniper, which is defended by oxalate, phenolics and monoterpenes, while closely related N. albigula specialize on cactus, which only contains oxalate. Woodrats maintain two gut chambers harboring dense microbial communities: a foregut chamber proximal to the major site of toxin absorption, and a cecal chamber in their hindgut. We performed several experiments to investigate the location and nature of microbial detoxification in the woodrat gut. First, we measured toxin concentrations across gut chambers of N. stephensi. Compared to food material, oxalate concentrations were immediately lower in the foregut, while concentrations of terpenes remained high in the foregut, and were lowest in the cecal chamber. We conducted metagenomic sequencing of the foregut chambers of both woodrat species and cecal chambers of N. stephensi to compare microbial functions. We found that most genes associated with detoxification were more abundant in the cecal chambers of N. stephensi. However, some genes associated with degradation of oxalate and phenolic compounds were more abundant in the foregut chambers. Thus, microbial detoxification may take place in various chambers depending on the class of chemical compound.}, } @article {pmid30202905, year = {2018}, author = {Cole, LW and Guo, W and Mower, JP and Palmer, JD}, title = {High and Variable Rates of Repeat-Mediated Mitochondrial Genome Rearrangement in a Genus of Plants.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2773-2785}, doi = {10.1093/molbev/msy176}, pmid = {30202905}, issn = {1537-1719}, abstract = {For 30 years, it has been clear that angiosperm mitochondrial genomes evolve rapidly in sequence arrangement (i.e., synteny), yet absolute rates of rearrangement have not been measured in any plant group, nor is it known how much these rates vary. To investigate these issues, we sequenced and reconstructed the rearrangement history of seven mitochondrial genomes in Monsonia (Geraniaceae). We show that rearrangements (occurring mostly as inversions) not only take place at generally high rates in these genomes but also uncover significant variation in rearrangement rates. For example, the hyperactive mitochondrial genome of Monsonia ciliata has accumulated at least 30 rearrangements over the last million years, whereas the branch leading to M. ciliata and its sister species has sustained rearrangement at a rate that is at least ten times lower. Furthermore, our analysis of published data shows that rates of mitochondrial genome rearrangement in seed plants vary by at least 600-fold. We find that sites of rearrangement are highly preferentially located in very close proximity to repeated sequences in Monsonia. This provides strong support for the hypothesis that rearrangement in angiosperm mitochondrial genomes occurs largely through repeat-mediated recombination. Because there is little variation in the amount of repeat sequence among Monsonia genomes, the variable rates of rearrangement in Monsonia probably reflect variable rates of mitochondrial recombination itself. Finally, we show that mitochondrial synonymous substitutions occur in a clock-like manner in Monsonia; rates of mitochondrial substitutions and rearrangements are therefore highly uncoupled in this group.}, } @article {pmid30202901, year = {2018}, author = {}, title = {Evolution of gustatory receptor gene family provides insights into adaptation to diverse host plants in nymphalid butterflies.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2240}, doi = {10.1093/gbe/evy181}, pmid = {30202901}, issn = {1759-6653}, } @article {pmid30202093, year = {2018}, author = {Zhao, Q and Zhou, H and Chi, S and Wang, Y and Wang, J and Geng, J and Wu, K and Liu, W and Zhang, T and Dong, MQ and Wang, J and Li, X and Xiao, B}, title = {Author Correction: Structure and mechanogating mechanism of the Piezo1 channel.}, journal = {Nature}, volume = {563}, number = {7730}, pages = {E19}, doi = {10.1038/s41586-018-0513-4}, pmid = {30202093}, issn = {1476-4687}, abstract = {In Extended Data Fig. 9a of this Article, the bottom micrographs of mPiezo1-ΔL3-4-IRES-GFP and mPiezo1-ΔL7-8-IRES-GFP (labelled 'permeabilized') are inadvertently the same images. The corrected figure panels are shown in the accompanying Amendment.}, } @article {pmid30202092, year = {2018}, author = {Saleem, AB and Diamanti, EM and Fournier, J and Harris, KD and Carandini, M}, title = {Coherent encoding of subjective spatial position in visual cortex and hippocampus.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {124-127}, doi = {10.1038/s41586-018-0516-1}, pmid = {30202092}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; 095669//Wellcome Trust/United Kingdom ; 205093//Wellcome Trust/United Kingdom ; }, abstract = {A major role of vision is to guide navigation, and navigation is strongly driven by vision1-4. Indeed, the brain's visual and navigational systems are known to interact5,6, and signals related to position in the environment have been suggested to appear as early as in the visual cortex6,7. Here, to establish the nature of these signals, we recorded in the primary visual cortex (V1) and hippocampal area CA1 while mice traversed a corridor in virtual reality. The corridor contained identical visual landmarks in two positions, so that a purely visual neuron would respond similarly at those positions. Most V1 neurons, however, responded solely or more strongly to the landmarks in one position rather than the other. This modulation of visual responses by spatial location was not explained by factors such as running speed. To assess whether the modulation is related to navigational signals and to the animal's subjective estimate of position, we trained the mice to lick for a water reward upon reaching a reward zone in the corridor. Neuronal populations in both CA1 and V1 encoded the animal's position along the corridor, and the errors in their representations were correlated. Moreover, both representations reflected the animal's subjective estimate of position, inferred from the animal's licks, better than its actual position. When animals licked in a given location-whether correctly or incorrectly-neural populations in both V1 and CA1 placed the animal in the reward zone. We conclude that visual responses in V1 are controlled by navigational signals, which are coherent with those encoded in hippocampus and reflect the animal's subjective position. The presence of such navigational signals as early as a primary sensory area suggests that they permeate sensory processing in the cortex.}, } @article {pmid30202091, year = {2018}, author = {Hafez, HA and Kovalev, S and Deinert, JC and Mics, Z and Green, B and Awari, N and Chen, M and Germanskiy, S and Lehnert, U and Teichert, J and Wang, Z and Tielrooij, KJ and Liu, Z and Chen, Z and Narita, A and Müllen, K and Bonn, M and Gensch, M and Turchinovich, D}, title = {Extremely efficient terahertz high-harmonic generation in graphene by hot Dirac fermions.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {507-511}, doi = {10.1038/s41586-018-0508-1}, pmid = {30202091}, issn = {1476-4687}, abstract = {Multiple optical harmonic generation-the multiplication of photon energy as a result of nonlinear interaction between light and matter-is a key technology in modern electronics and optoelectronics, because it allows the conversion of optical or electronic signals into signals with much higher frequency, and the generation of frequency combs. Owing to the unique electronic band structure of graphene, which features massless Dirac fermions1-3, it has been repeatedly predicted that optical harmonic generation in graphene should be particularly efficient at the technologically important terahertz frequencies4-6. However, these predictions have yet to be confirmed experimentally under technologically relevant operation conditions. Here we report the generation of terahertz harmonics up to the seventh order in single-layer graphene at room temperature and under ambient conditions, driven by terahertz fields of only tens of kilovolts per centimetre, and with field conversion efficiencies in excess of 10-3, 10-4 and 10-5 for the third, fifth and seventh terahertz harmonics, respectively. These conversion efficiencies are remarkably high, given that the electromagnetic interaction occurs in a single atomic layer. The key to such extremely efficient generation of terahertz high harmonics in graphene is the collective thermal response of its background Dirac electrons to the driving terahertz fields. The terahertz harmonics, generated via hot Dirac fermion dynamics, were observed directly in the time domain as electromagnetic field oscillations at these newly synthesized higher frequencies. The effective nonlinear optical coefficients of graphene for the third, fifth and seventh harmonics exceed the respective nonlinear coefficients of typical solids by 7-18 orders of magnitude7-9. Our results provide a direct pathway to highly efficient terahertz frequency synthesis using the present generation of graphene electronics, which operate at much lower fundamental frequencies of only a few hundreds of gigahertz.}, } @article {pmid30202090, year = {2018}, author = {Mittal, S and Goldschmidt, EA and Hafezi, M}, title = {A topological source of quantum light.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {502-506}, doi = {10.1038/s41586-018-0478-3}, pmid = {30202090}, issn = {1476-4687}, abstract = {Quantum light is characterized by distinctive statistical distributions that are possible only because of quantum mechanical effects. For example, single photons and correlated photon pairs exhibit photon number distributions with variance lower than classically allowed limits. This enables high-fidelity transmission of quantum information and sensing with lower noise than possible with classical light sources1,2. Most quantum light sources rely on spontaneous parametric processes such as down-conversion and four-wave mixing2. These processes are mediated by vacuum fluctuations of the electromagnetic field. Therefore, by manipulating the electromagnetic mode structure, for example with dispersion-engineered nanophotonic systems, the spectrum of generated photons can be controlled3-7. However, disorder, which is ubiquitous in nanophotonic fabrication, causes device-to-device spectral variations8-11. Here we realize topologically robust electromagnetic modes and use their vacuum fluctuations to create a quantum light source in which the spectrum of generated photons is much less affected by fabrication-induced disorder. Specifically, we use the topological edge states realized in a two-dimensional array of ring resonators to generate correlated photon pairs by spontaneous four-wave mixing and show that they outperform their topologically trivial one-dimensional counterparts in terms of spectral robustness. We demonstrate the non-classical nature of the generated light and the realization of a robust source of heralded single photons by measuring the conditional antibunching of photons, that is, the reduced likelihood of photons arriving together compared to thermal or laser light. Such topological effects, which are unique to bosonic systems, could pave the way for the development of robust quantum photonic devices.}, } @article {pmid30202089, year = {2018}, author = {Cai, Y and Hossain, MJ and Hériché, JK and Politi, AZ and Walther, N and Koch, B and Wachsmuth, M and Nijmeijer, B and Kueblbeck, M and Martinic-Kavur, M and Ladurner, R and Alexander, S and Peters, JM and Ellenberg, J}, title = {Experimental and computational framework for a dynamic protein atlas of human cell division.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {411-415}, doi = {10.1038/s41586-018-0518-z}, pmid = {30202089}, issn = {1476-4687}, abstract = {Essential biological functions, such as mitosis, require tight coordination of hundreds of proteins in space and time. Localization, the timing of interactions and changes in cellular structure are all crucial to ensure the correct assembly, function and regulation of protein complexes1-4. Imaging of live cells can reveal protein distributions and dynamics but experimental and theoretical challenges have prevented the collection of quantitative data, which are necessary for the formulation of a model of mitosis that comprehensively integrates information and enables the analysis of the dynamic interactions between the molecular parts of the mitotic machinery within changing cellular boundaries. Here we generate a canonical model of the morphological changes during the mitotic progression of human cells on the basis of four-dimensional image data. We use this model to integrate dynamic three-dimensional concentration data of many fluorescently knocked-in mitotic proteins, imaged by fluorescence correlation spectroscopy-calibrated microscopy5. The approach taken here to generate a dynamic protein atlas of human cell division is generic; it can be applied to systematically map and mine dynamic protein localization networks that drive cell division in different cell types, and can be conceptually transferred to other cellular functions.}, } @article {pmid30202088, year = {2018}, author = {Kouyos, RD and Rusert, P and Kadelka, C and Huber, M and Marzel, A and Ebner, H and Schanz, M and Liechti, T and Friedrich, N and Braun, DL and Scherrer, AU and Weber, J and Uhr, T and Baumann, NS and Leemann, C and Kuster, H and Chave, JP and Cavassini, M and Bernasconi, E and Hoffmann, M and Calmy, A and Battegay, M and Rauch, A and Yerly, S and Aubert, V and Klimkait, T and Böni, J and Metzner, KJ and Günthard, HF and Trkola, A and , }, title = {Tracing HIV-1 strains that imprint broadly neutralizing antibody responses.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {406-410}, doi = {10.1038/s41586-018-0517-0}, pmid = {30202088}, issn = {1476-4687}, abstract = {Understanding the determinants of broadly neutralizing antibody (bNAb) evolution is crucial for the development of bNAb-based HIV vaccines1. Despite emerging information on cofactors that promote bNAb evolution in natural HIV-1 infections, in which the induction of bNAbs is genuinely rare2, information on the impact of the infecting virus strain on determining the breadth and specificity of the antibody responses to HIV-1 is lacking. Here we analyse the influence of viral antigens in shaping antibody responses in humans. We call the ability of a virus strain to induce similar antibody responses across different hosts its antibody-imprinting capacity, which from an evolutionary biology perspective corresponds to the viral heritability of the antibody responses. Analysis of 53 measured parameters of HIV-1-binding and neutralizing antibody responses in a cohort of 303 HIV-1 transmission pairs (individuals who harboured highly related HIV-1 strains and were putative direct transmission partners or members of an HIV-1 transmission chain) revealed that the effect of the infecting virus on the outcome of the bNAb response is moderate in magnitude but highly significant. We introduce the concept of bNAb-imprinting viruses and provide evidence for the existence of such viruses in a systematic screening of our cohort. The bNAb-imprinting capacity can be substantial, as indicated by a transmission pair with highly similar HIV-1 antibody responses and strong bNAb activity. Identification of viruses that have bNAb-imprinting capacities and their characterization may thus provide the potential to develop lead immunogens.}, } @article {pmid30202056, year = {2018}, author = {Dixon, JR and Xu, J and Dileep, V and Zhan, Y and Song, F and Le, VT and Yardımcı, GG and Chakraborty, A and Bann, DV and Wang, Y and Clark, R and Zhang, L and Yang, H and Liu, T and Iyyanki, S and An, L and Pool, C and Sasaki, T and Rivera-Mulia, JC and Ozadam, H and Lajoie, BR and Kaul, R and Buckley, M and Lee, K and Diegel, M and Pezic, D and Ernst, C and Hadjur, S and Odom, DT and Stamatoyannopoulos, JA and Broach, JR and Hardison, RC and Ay, F and Noble, WS and Dekker, J and Gilbert, DM and Yue, F}, title = {Integrative detection and analysis of structural variation in cancer genomes.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1388-1398}, doi = {10.1038/s41588-018-0195-8}, pmid = {30202056}, issn = {1546-1718}, support = {DP5 OD023071/OD/NIH HHS/United States ; 615584//European Research Council/International ; R01 HG009906/HG/NHGRI NIH HHS/United States ; R01 HG003143/HG/NHGRI NIH HHS/United States ; U54 DK107980/DK/NIDDK NIH HHS/United States ; P01 GM085354/GM/NIGMS NIH HHS/United States ; U01 CA200060/CA/NCI NIH HHS/United States ; U54 DK107965/DK/NIDDK NIH HHS/United States ; R24 DK106766/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R01 GM083337/GM/NIGMS NIH HHS/United States ; U54 HG004592/HG/NHGRI NIH HHS/United States ; R35 GM124820/GM/NIGMS NIH HHS/United States ; U41 HG007000/HG/NHGRI NIH HHS/United States ; }, abstract = {Structural variants (SVs) can contribute to oncogenesis through a variety of mechanisms. Despite their importance, the identification of SVs in cancer genomes remains challenging. Here, we present a framework that integrates optical mapping, high-throughput chromosome conformation capture (Hi-C), and whole-genome sequencing to systematically detect SVs in a variety of normal or cancer samples and cell lines. We identify the unique strengths of each method and demonstrate that only integrative approaches can comprehensively identify SVs in the genome. By combining Hi-C and optical mapping, we resolve complex SVs and phase multiple SV events to a single haplotype. Furthermore, we observe widespread structural variation events affecting the functions of noncoding sequences, including the deletion of distal regulatory sequences, alteration of DNA replication timing, and the creation of novel three-dimensional chromatin structural domains. Our results indicate that noncoding SVs may be underappreciated mutational drivers in cancer genomes.}, } @article {pmid30202055, year = {2018}, author = {Blumenstock, J}, title = {Don't forget people in the use of big data for development.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {170-172}, doi = {10.1038/d41586-018-06215-5}, pmid = {30202055}, issn = {1476-4687}, } @article {pmid30202054, year = {2018}, author = {Extance, A}, title = {How AI technology can tame the scientific literature.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {273-274}, doi = {10.1038/d41586-018-06617-5}, pmid = {30202054}, issn = {1476-4687}, } @article {pmid30202053, year = {2018}, author = {Blanchard, G}, title = {A 3D cell shape that enables tube formation.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {182-183}, doi = {10.1038/d41586-018-06162-1}, pmid = {30202053}, issn = {1476-4687}, mesh = {*Cell Shape ; *Epithelium ; Histone Deacetylase Inhibitors ; Morphogenesis ; }, } @article {pmid30202017, year = {2018}, author = {Stanelle-Bertram, S and Walendy-Gnirß, K and Speiseder, T and Thiele, S and Asante, IA and Dreier, C and Kouassi, NM and Preuß, A and Pilnitz-Stolze, G and Müller, U and Thanisch, S and Richter, M and Scharrenberg, R and Kraus, V and Dörk, R and Schau, L and Herder, V and Gerhauser, I and Pfankuche, VM and Käufer, C and Waltl, I and Moraes, T and Sellau, J and Hoenow, S and Schmidt-Chanasit, J and Jansen, S and Schattling, B and Ittrich, H and Bartsch, U and Renné, T and Bartenschlager, R and Arck, P and Cadar, D and Friese, MA and Vapalahti, O and Lotter, H and Benites, S and Rolling, L and Gabriel, M and Baumgärtner, W and Morellini, F and Hölter, SM and Amarie, O and Fuchs, H and Hrabe de Angelis, M and Löscher, W and Calderon de Anda, F and Gabriel, G}, title = {Male offspring born to mildly ZIKV-infected mice are at risk of developing neurocognitive disorders in adulthood.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1161-1174}, doi = {10.1038/s41564-018-0236-1}, pmid = {30202017}, issn = {2058-5276}, abstract = {Congenital Zika virus (ZIKV) syndrome may cause fetal microcephaly in ~1% of affected newborns. Here, we investigate whether the majority of clinically inapparent newborns might suffer from long-term health impairments not readily visible at birth. Infection of immunocompetent pregnant mice with high-dose ZIKV caused severe offspring phenotypes, such as fetal death, as expected. By contrast, low-dose (LD) maternal ZIKV infection resulted in reduced fetal birth weight but no other obvious phenotypes. Male offspring born to LD ZIKV-infected mothers had increased testosterone (TST) levels and were less likely to survive in utero infection compared to their female littermates. Males also presented an increased number of immature neurons in apical and basal hippocampal dendrites, while female offspring had immature neurons in basal dendrites only. Moreover, male offspring with high but not very high (storm) TST levels were more likely to suffer from learning and memory impairments compared to females. Future studies are required to understand the impact of TST on neuropathological and neurocognitive impairments in later life. In summary, increased sex-specific vigilance is required in countries with high ZIKV prevalence, where impaired neurodevelopment may be camouflaged by a healthy appearance at birth.}, } @article {pmid30202016, year = {2018}, author = {Sallin, MA and Kauffman, KD and Riou, C and Du Bruyn, E and Foreman, TW and Sakai, S and Hoft, SG and Myers, TG and Gardina, PJ and Sher, A and Moore, R and Wilder-Kofie, T and Moore, IN and Sette, A and Lindestam Arlehamn, CS and Wilkinson, RJ and Barber, DL}, title = {Host resistance to pulmonary Mycobacterium tuberculosis infection requires CD153 expression.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1198-1205}, doi = {10.1038/s41564-018-0231-6}, pmid = {30202016}, issn = {2058-5276}, abstract = {Mycobacterium tuberculosis infection (Mtb) is the leading cause of death due to a single infectious agent and is among the top ten causes of all human deaths worldwide1. CD4 T cells are essential for resistance to Mtb infection, and for decades it has been thought that IFNγ production is the primary mechanism of CD4 T-cell-mediated protection2,3. However, IFNγ responses do not correlate with host protection, and several reports demonstrate that additional anti-tuberculosis CD4 T-cell effector functions remain unaccounted for4-8. Here we show that the tumour-necrosis factor (TNF) superfamily molecule CD153 (encoded by the gene Tnfsf8) is required for control of pulmonary Mtb infection by CD4 T cells. In Mtb-infected mice, CD153 expression is highest on Mtb-specific T helper 1 (TH1) cells in the lung tissue parenchyma, but its induction does not require TH1 cell polarization. CD153-deficient mice develop high pulmonary bacterial loads and succumb early to Mtb infection. Reconstitution of T-cell-deficient hosts with either Tnfsf8-/- or Ifng-/- CD4 T cells alone fails to rescue mice from early mortality, but reconstitution with a mixture of Tnfsf8-/- and Ifng-/- CD4 T cells provides similar protection as wild-type T cells. In Mtb-infected non-human primates, CD153 expression is much higher on Ag-specific CD4 T cells in the airways compared to blood, and the frequency of Mtb-specific CD153-expressing CD4 T cells inversely correlates with bacterial loads in granulomas. In Mtb-infected humans, CD153 defines a subset of highly polyfunctional Mtb-specific CD4 T cells that are much more abundant in individuals with controlled latent Mtb infection compared to those with active tuberculosis. In all three species, Mtb-specific CD8 T cells did not upregulate CD153 following peptide stimulation. Thus, CD153 is a major immune mediator of host protection against pulmonary Mtb infection and CD4 T cells are one important source of this molecule.}, } @article {pmid30202015, year = {2018}, author = {Martin, PK and Marchiando, A and Xu, R and Rudensky, E and Yeung, F and Schuster, SL and Kernbauer, E and Cadwell, K}, title = {Autophagy proteins suppress protective type I interferon signalling in response to the murine gut microbiota.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1131-1141}, pmid = {30202015}, issn = {2058-5276}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; F31 DK111139/DK/NIDDK NIH HHS/United States ; R01 DK093668/DK/NIDDK NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; S10 OD018338/OD/NIH HHS/United States ; R01 AI121244/AI/NIAID NIH HHS/United States ; S10 OD010584/OD/NIH HHS/United States ; T32 AI100853/AI/NIAID NIH HHS/United States ; S10 RR023704/RR/NCRR NIH HHS/United States ; R01 DK103788/DK/NIDDK NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, abstract = {As a conserved pathway that lies at the intersection between host defence and cellular homeostasis, autophagy serves as a rheostat for immune reactions. In particular, autophagy suppresses excess type I interferon (IFN-I) production in response to viral nucleic acids. It is unknown how this function of autophagy relates to the intestinal barrier where host-microbe interactions are pervasive and perpetual. Here, we demonstrate that mice deficient in autophagy proteins are protected from the intestinal bacterial pathogen Citrobacter rodentium in a manner dependent on IFN-I signalling and nucleic acid sensing pathways. Enhanced IFN-stimulated gene expression in intestinal tissue of autophagy-deficient mice in the absence of infection was mediated by the gut microbiota. Additionally, monocytes infiltrating into the autophagy-deficient intestinal microenvironment displayed an enhanced inflammatory profile and were necessary for protection against C. rodentium. Finally, we demonstrate that the microbiota-dependent IFN-I production that occurs in the autophagy-deficient host also protects against chemical injury of the intestine. Thus, autophagy proteins prevent a spontaneous IFN-I response to microbiota that is beneficial in the presence of infectious and non-infectious intestinal hazards. These results identify a role for autophagy proteins in controlling the magnitude of IFN-I signalling at the intestinal barrier.}, } @article {pmid30201967, year = {2018}, author = {Froehlich, HE and Gentry, RR and Halpern, BS}, title = {Global change in marine aquaculture production potential under climate change.}, journal = {Nature ecology & evolution}, volume = {2}, number = {11}, pages = {1745-1750}, doi = {10.1038/s41559-018-0669-1}, pmid = {30201967}, issn = {2397-334X}, abstract = {Climate change is an immediate and future threat to food security globally. The consequences for fisheries and agriculture production potential are well studied, yet the possible outcomes for aquaculture (that is, aquatic farming)-one of the fastest growing food sectors on the planet-remain a major gap in scientific understanding. With over one-third of aquaculture produced in marine waters and this proportion increasing, it is critical to anticipate new opportunities and challenges in marine production under climate change. Here, we model and map the effect of warming ocean conditions (Representative Concentration Pathway scenario 8.5) on marine aquaculture production potential over the next century, based on thermal tolerance and growth data of 180 cultured finfish and bivalve species. We find heterogeneous patterns of gains and losses, but an overall greater probability of declines worldwide. Accounting for multiple drivers of species growth, including shifts in temperature, chlorophyll and ocean acidification, reveals potentially greater declines in bivalve aquaculture compared with finfish production. This study addresses a missing component in food security research and sustainable development planning by identifying regions that will face potentially greater climate change challenges and resilience with regards to marine aquaculture in the coming decades. Understanding the scale and magnitude of future increases and reductions in aquaculture potential is critical for designing effective and efficient use and protection of the oceans, and ultimately for feeding the planet sustainably.}, } @article {pmid30201966, year = {2018}, author = {Igler, C and Lagator, M and Tkačik, G and Bollback, JP and Guet, CC}, title = {Evolutionary potential of transcription factors for gene regulatory rewiring.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1633-1643}, doi = {10.1038/s41559-018-0651-y}, pmid = {30201966}, issn = {2397-334X}, abstract = {Gene regulatory networks evolve through rewiring of individual components-that is, through changes in regulatory connections. However, the mechanistic basis of regulatory rewiring is poorly understood. Using a canonical gene regulatory system, we quantify the properties of transcription factors that determine the evolutionary potential for rewiring of regulatory connections: robustness, tunability and evolvability. In vivo repression measurements of two repressors at mutated operator sites reveal their contrasting evolutionary potential: while robustness and evolvability were positively correlated, both were in trade-off with tunability. Epistatic interactions between adjacent operators alleviated this trade-off. A thermodynamic model explains how the differences in robustness, tunability and evolvability arise from biophysical characteristics of repressor-DNA binding. The model also uncovers that the energy matrix, which describes how mutations affect repressor-DNA binding, encodes crucial information about the evolutionary potential of a repressor. The biophysical determinants of evolutionary potential for regulatory rewiring constitute a mechanistic framework for understanding network evolution.}, } @article {pmid30201965, year = {2018}, author = {}, title = {Knowing ourselves.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1517-1518}, doi = {10.1038/s41559-018-0675-3}, pmid = {30201965}, issn = {2397-334X}, } @article {pmid30201964, year = {2018}, author = {Sandgathe, D and McPherron, S and Goldberg, P and Aldeias, V}, title = {Harold L. Dibble (1951-2018).}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1521-1522}, doi = {10.1038/s41559-018-0665-5}, pmid = {30201964}, issn = {2397-334X}, } @article {pmid30201963, year = {2018}, author = {Čapek, P and Manzoni, S and Kaštovská, E and Wild, B and Diáková, K and Bárta, J and Schnecker, J and Biasi, C and Martikainen, PJ and Alves, RJE and Guggenberger, G and Gentsch, N and Hugelius, G and Palmtag, J and Mikutta, R and Shibistova, O and Urich, T and Schleper, C and Richter, A and Šantrůčková, H}, title = {A plant-microbe interaction framework explaining nutrient effects on primary production.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1588-1596}, doi = {10.1038/s41559-018-0662-8}, pmid = {30201963}, issn = {2397-334X}, abstract = {In most terrestrial ecosystems, plant growth is limited by nitrogen and phosphorus. Adding either nutrient to soil usually affects primary production, but their effects can be positive or negative. Here we provide a general stoichiometric framework for interpreting these contrasting effects. First, we identify nitrogen and phosphorus limitations on plants and soil microorganisms using their respective nitrogen to phosphorus critical ratios. Second, we use these ratios to show how soil microorganisms mediate the response of primary production to limiting and non-limiting nutrient addition along a wide gradient of soil nutrient availability. Using a meta-analysis of 51 factorial nitrogen-phosphorus fertilization experiments conducted across multiple ecosystems, we demonstrate that the response of primary production to nitrogen and phosphorus additions is accurately predicted by our stoichiometric framework. The only pattern that could not be predicted by our original framework suggests that nitrogen has not only a structural function in growing organisms, but also a key role in promoting plant and microbial nutrient acquisition. We conclude that this stoichiometric framework offers the most parsimonious way to interpret contrasting and, until now, unresolved responses of primary production to nutrient addition in terrestrial ecosystems.}, } @article {pmid30201962, year = {2018}, author = {Schmitz, JF and Ullrich, KK and Bornberg-Bauer, E}, title = {Incipient de novo genes can evolve from frozen accidents that escaped rapid transcript turnover.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1626-1632}, doi = {10.1038/s41559-018-0639-7}, pmid = {30201962}, issn = {2397-334X}, abstract = {A recent surge of studies have suggested that many novel genes arise de novo from previously noncoding DNA and not by duplication. However, most studies concentrated on longer evolutionary time scales and rarely considered protein structural properties. Therefore, it remains unclear how these properties are shaped by evolution, depend on genetic mechanisms and influence gene survival. Here we compare open reading frames (ORFs) from high coverage transcriptomes from mouse and another four mammals covering 160 million years of evolution. We find that novel ORFs pervasively emerge from noncoding regions but are rapidly lost again, while relatively fewer arise from the divergence of coding sequences but are retained much longer. We also find that a subset (14%) of the mouse-specific ORFs bind ribosomes and are potentially translated, showing that such ORFs can be the starting points of gene emergence. Surprisingly, disorder and other protein properties of young ORFs hardly change with gene age in short time frames. Only length and nucleotide composition change significantly. Thus, some transcribed de novo genes resemble 'frozen accidents' of randomly emerged ORFs that survived initial purging. This perspective complies with very recent studies indicating that some neutrally evolving transcripts containing random protein sequences may be translated and be viable starting points of de novo gene emergence.}, } @article {pmid30201846, year = {2018}, author = {Denham, JE and Ranner, T and Cohen, N}, title = {Signatures of proprioceptive control in Caenorhabditis elegans locomotion.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201846}, issn = {1471-2970}, abstract = {Animal neuromechanics describes the coordinated self-propelled movement of a body, subject to the combined effects of internal neural control and mechanical forces. Here we use a computational model to identify effects of neural and mechanical modulation on undulatory forward locomotion of Caenorhabditis elegans, with a focus on proprioceptively driven neural control. We reveal a fundamental relationship between body elasticity and environmental drag in determining the dynamics of the body and demonstrate the manifestation of this relationship in the context of proprioceptively driven control. By considering characteristics unique to proprioceptive neurons, we predict the signatures of internal gait modulation that contrast with the known signatures of externally or biomechanically modulated gait. We further show that proprioceptive feedback can suppress neuromechanical phase lags during undulatory locomotion, contrasting with well studied advancing phase lags that have long been a signature of centrally generated, feed-forward control.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201845, year = {2018}, author = {Sarma, GP and Lee, CW and Portegys, T and Ghayoomie, V and Jacobs, T and Alicea, B and Cantarelli, M and Currie, M and Gerkin, RC and Gingell, S and Gleeson, P and Gordon, R and Hasani, RM and Idili, G and Khayrulin, S and Lung, D and Palyanov, A and Watts, M and Larson, SD}, title = {OpenWorm: overview and recent advances in integrative biological simulation of Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201845}, issn = {1471-2970}, abstract = {The adoption of powerful software tools and computational methods from the software industry by the scientific research community has resulted in a renewed interest in integrative, large-scale biological simulations. These typically involve the development of computational platforms to combine diverse, process-specific models into a coherent whole. The OpenWorm Foundation is an independent research organization working towards an integrative simulation of the nematode Caenorhabditis elegans, with the aim of providing a powerful new tool to understand how the organism's behaviour arises from its fundamental biology. In this perspective, we give an overview of the history and philosophy of OpenWorm, descriptions of the constituent sub-projects and corresponding open-science management practices, and discuss current achievements of the project and future directions.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201844, year = {2018}, author = {Gerkin, RC and Jarvis, RJ and Crook, SM}, title = {Towards systematic, data-driven validation of a collaborative, multi-scale model of Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201844}, issn = {1471-2970}, abstract = {The OpenWorm Project is an international open-source collaboration to create a multi-scale model of the organism Caenorhabditis elegans At each scale, including subcellular, cellular, network and behaviour, this project employs one or more computational models that aim to recapitulate the corresponding biological system at that scale. This requires that the simulated behaviour of each model be compared with experimental data both as the model is continuously refined and as new experimental data become available. Here we report the use of SciUnit, a software framework for model validation, to attempt to achieve these goals. During project development, each model is continuously subjected to data-driven 'unit tests' that quantitatively summarize model-data agreement, identifying modelling progress and highlighting particular aspects of each model that fail to adequately reproduce known features of the biological organism and its components. This workflow is publicly visible via both GitHub and a web application and accepts community contributions to ensure that modelling goals are transparent and well-informed.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201843, year = {2018}, author = {Cantarelli, M and Marin, B and Quintana, A and Earnshaw, M and Court, R and Gleeson, P and Dura-Bernal, S and Silver, RA and Idili, G}, title = {Geppetto: a reusable modular open platform for exploring neuroscience data and models.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201843}, issn = {1471-2970}, support = {294667//European Research Council/International ; BB/G02233X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 208379//Wellcome Trust/United Kingdom ; 105023PARKINSON//Wellcome Trust/United Kingdom ; 105023ARMSTRONG//Wellcome Trust/United Kingdom ; BB/G02247X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 203048//Wellcome Trust/United Kingdom ; 086699//Wellcome Trust/United Kingdom ; 101445//Wellcome Trust/United Kingdom ; 105023O'KANE//Wellcome Trust/United Kingdom ; 105023JEFFERIS//Wellcome Trust/United Kingdom ; 095667//Wellcome Trust/United Kingdom ; }, abstract = {Geppetto is an open-source platform that provides generic middleware infrastructure for building both online and desktop tools for visualizing neuroscience models and data and managing simulations. Geppetto underpins a number of neuroscience applications, including Open Source Brain (OSB), Virtual Fly Brain (VFB), NEURON-UI and NetPyNE-UI. OSB is used by researchers to create and visualize computational neuroscience models described in NeuroML and simulate them through the browser. VFB is the reference hub for Drosophila melanogaster neural anatomy and imaging data including neuropil, segmented neurons, microscopy stacks and gene expression pattern data. Geppetto is also being used to build a new user interface for NEURON, a widely used neuronal simulation environment, and for NetPyNE, a Python package for network modelling using NEURON. Geppetto defines domain agnostic abstractions used by all these applications to represent their models and data and offers a set of modules and components to integrate, visualize and control simulations in a highly accessible way. The platform comprises a backend which can connect to external data sources, model repositories and simulators together with a highly customizable frontend.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201842, year = {2018}, author = {Gleeson, P and Lung, D and Grosu, R and Hasani, R and Larson, SD}, title = {c302: a multiscale framework for modelling the nervous system of Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201842}, issn = {1471-2970}, abstract = {The OpenWorm project has the ambitious goal of producing a highly detailed in silico model of the nematode Caenorhabditis elegans A crucial part of this work will be a model of the nervous system encompassing all known cell types and connections. The appropriate level of biophysical detail required in the neuronal model to reproduce observed high-level behaviours in the worm has yet to be determined. For this reason, we have developed a framework, c302, that allows different instances of neuronal networks to be generated incorporating varying levels of anatomical and physiological detail, which can be investigated and refined independently or linked to other tools developed in the OpenWorm modelling toolchain.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201841, year = {2018}, author = {Liu, H and Kim, J and Shlizerman, E}, title = {Functional connectomics from neural dynamics: probabilistic graphical models for neuronal network of Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201841}, issn = {1471-2970}, abstract = {We propose an approach to represent neuronal network dynamics as a probabilistic graphical model (PGM). To construct the PGM, we collect time series of neuronal responses produced by the neuronal network and use singular value decomposition to obtain a low-dimensional projection of the time-series data. We then extract dominant patterns from the projections to get pairwise dependency information and create a graphical model for the full network. The outcome model is a functional connectome that captures how stimuli propagate through the network and thus represents causal dependencies between neurons and stimuli. We apply our methodology to a model of the Caenorhabditis elegans somatic nervous system to validate and show an example of our approach. The structure and dynamics of the C. elegans nervous system are well studied and a model that generates neuronal responses is available. The resulting PGM enables us to obtain and verify underlying neuronal pathways for known behavioural scenarios and detect possible pathways for novel scenarios.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201840, year = {2018}, author = {Palyanov, A and Khayrulin, S and Larson, SD}, title = {Three-dimensional simulation of the Caenorhabditis elegans body and muscle cells in liquid and gel environments for behavioural analysis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201840}, issn = {1471-2970}, abstract = {To better understand how a nervous system controls the movements of an organism, we have created a three-dimensional computational biomechanical model of the Caenorhabditis elegans body based on real anatomical structure. The body model is created with a particle system-based simulation engine known as Sibernetic, which implements the smoothed particle-hydrodynamics algorithm. The model includes an elastic body-wall cuticle subject to hydrostatic pressure. This cuticle is then driven by body-wall muscle cells that contract and relax, whose positions and shape are mapped from C. elegans anatomy, and determined from light microscopy and electron micrograph data. We show that by using different muscle activation patterns, this model is capable of producing C. elegans-like behaviours, including crawling and swimming locomotion in environments with different viscosities, while fitting multiple additional known biomechanical properties of the animal. This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201839, year = {2018}, author = {Javer, A and Ripoll-Sánchez, L and Brown, AEX}, title = {Powerful and interpretable behavioural features for quantitative phenotyping of Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201839}, issn = {1471-2970}, abstract = {Behaviour is a sensitive and integrative readout of nervous system function and therefore an attractive measure for assessing the effects of mutation or drug treatment on animals. Video data provide a rich but high-dimensional representation of behaviour, and so the first step of analysis is often some form of tracking and feature extraction to reduce dimensionality while maintaining relevant information. Modern machine-learning methods are powerful but notoriously difficult to interpret, while handcrafted features are interpretable but do not always perform as well. Here, we report a new set of handcrafted features to compactly quantify Caenorhabditis elegans behaviour. The features are designed to be interpretable but to capture as much of the phenotypic differences between worms as possible. We show that the full feature set is more powerful than a previously defined feature set in classifying mutant strains. We then use a combination of automated and manual feature selection to define a core set of interpretable features that still provides sufficient power to detect behavioural differences between mutant strains and the wild-type. Finally, we apply the new features to detect time-resolved behavioural differences in a series of optogenetic experiments targeting different neural subsets.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201838, year = {2018}, author = {Izquierdo, EJ and Beer, RD}, title = {From head to tail: a neuromechanical model of forward locomotion in Caenorhabditis elegans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201838}, issn = {1471-2970}, abstract = {With 302 neurons and a near-complete reconstruction of the neural and muscle anatomy at the cellular level, Caenorhabditis elegans is an ideal candidate organism to study the neuromechanical basis of behaviour. Yet despite the breadth of knowledge about the neurobiology, anatomy and physics of C. elegans, there are still a number of unanswered questions about one of its most basic and fundamental behaviours: forward locomotion. How the rhythmic pattern is generated and propagated along the body is not yet well understood. We report on the development and analysis of a model of forward locomotion that integrates the neuroanatomy, neurophysiology and body mechanics of the worm. Our model is motivated by experimental analysis of the structure of the ventral cord circuitry and the effect of local body curvature on nearby motoneurons. We developed a neuroanatomically grounded model of the head motoneuron circuit and the ventral nerve cord circuit. We integrated the neural model with an existing biomechanical model of the worm's body, with updated musculature and stretch receptors. Unknown parameters were evolved using an evolutionary algorithm to match the speed of the worm on agar. We performed 100 evolutionary runs and consistently found electrophysiological configurations that reproduced realistic control of forward movement. The ensemble of successful solutions reproduced key experimental observations that they were not designed to fit, including the wavelength and frequency of the propagating wave. Analysis of the ensemble revealed that head motoneurons SMD and RMD are sufficient to drive dorsoventral undulations in the head and neck and that short-range posteriorly directed proprioceptive feedback is sufficient to propagate the wave along the rest of the body.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201837, year = {2018}, author = {Towlson, EK and Vértes, PE and Yan, G and Chew, YL and Walker, DS and Schafer, WR and Barabási, AL}, title = {Caenorhabditis elegans and the network control framework-FAQs.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201837}, issn = {1471-2970}, support = {MR/K020706/1//Medical Research Council/United Kingdom ; }, abstract = {Control is essential to the functioning of any neural system. Indeed, under healthy conditions the brain must be able to continuously maintain a tight functional control between the system's inputs and outputs. One may therefore hypothesize that the brain's wiring is predetermined by the need to maintain control across multiple scales, maintaining the stability of key internal variables, and producing behaviour in response to environmental cues. Recent advances in network control have offered a powerful mathematical framework to explore the structure-function relationship in complex biological, social and technological networks, and are beginning to yield important and precise insights on neuronal systems. The network control paradigm promises a predictive, quantitative framework to unite the distinct datasets necessary to fully describe a nervous system, and provide mechanistic explanations for the observed structure and function relationships. Here, we provide a thorough review of the network control framework as applied to Caenorhabditis elegans (Yan et al. 2017 Nature550, 519-523. (doi:10.1038/nature24056)), in the style of Frequently Asked Questions. We present the theoretical, computational and experimental aspects of network control, and discuss its current capabilities and limitations, together with the next likely advances and improvements. We further present the Python code to enable exploration of control principles in a manner specific to this prototypical organism.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201836, year = {2018}, author = {Kaplan, HS and Nichols, ALA and Zimmer, M}, title = {Sensorimotor integration in Caenorhabditis elegans: a reappraisal towards dynamic and distributed computations.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201836}, issn = {1471-2970}, support = {281869//European Research Council/International ; }, abstract = {The nematode Caenorhabditis elegans is a tractable model system to study locomotion, sensory navigation and decision-making. In its natural habitat, it is thought to navigate complex multisensory environments in order to find food and mating partners, while avoiding threats like predators or toxic environments. While research in past decades has shed much light on the functions and mechanisms of selected sensory neurons, we are just at the brink of understanding how sensory information is integrated by interneuron circuits for action selection in the worm. Recent technological advances have enabled whole-brain Ca2+ imaging and Ca2+ imaging of neuronal activity in freely moving worms. A common principle emerging across multiple studies is that most interneuron activities are tightly coupled to the worm's instantaneous behaviour; notably, these observations encompass neurons receiving direct sensory neuron inputs. The new findings suggest that in the C. elegans brain, sensory and motor representations are integrated already at the uppermost sensory processing layers. Moreover, these results challenge a perhaps more intuitive view of sequential feed-forward sensory pathways that converge onto premotor interneurons and motor neurons. We propose that sensorimotor integration occurs rather in a distributed dynamical fashion. In this perspective article, we will explore this view, discuss the challenges and implications of these discoveries on the interpretation and design of neural activity experiments, and discuss possible functions. Furthermore, we will discuss the broader context of similar findings in fruit flies and rodents, which suggest generalizable principles that can be learnt from this amenable nematode model organism.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201835, year = {2018}, author = {Wen, Q and Gao, S and Zhen, M}, title = {Caenorhabditis elegans excitatory ventral cord motor neurons derive rhythm for body undulation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201835}, issn = {1471-2970}, abstract = {The intrinsic oscillatory activity of central pattern generators underlies motor rhythm. We review and discuss recent findings that address the origin of Caenorhabditis elegans motor rhythm. These studies propose that the A- and mid-body B-class excitatory motor neurons at the ventral cord function as non-bursting intrinsic oscillators to underlie body undulation during reversal and forward movements, respectively. Proprioception entrains their intrinsic activities, allows phase-coupling between members of the same class motor neurons, and thereby facilitates directional propagation of undulations. Distinct pools of premotor interneurons project along the ventral nerve cord to innervate all members of the A- and B-class motor neurons, modulating their oscillations, as well as promoting their bi-directional coupling. The two motor sub-circuits, which consist of oscillators and descending inputs with distinct properties, form the structural base of dynamic rhythmicity and flexible partition of the forward and backward motor states. These results contribute to a continuous effort to establish a mechanistic and dynamic model of the C. elegans sensorimotor system. C. elegans exhibits rich sensorimotor functions despite a small neuron number. These findings implicate a circuit-level functional compression. By integrating the role of rhythm generation and proprioception into motor neurons, and the role of descending regulation of oscillators into premotor interneurons, this numerically simple nervous system can achieve a circuit infrastructure analogous to that of anatomically complex systems. C. elegans has manifested itself as a compact model to search for general principles of sensorimotor behaviours.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201834, year = {2018}, author = {Chew, YL and Grundy, LJ and Brown, AEX and Beets, I and Schafer, WR}, title = {Neuropeptides encoded by nlp-49 modulate locomotion, arousal and egg-laying behaviours in Caenorhabditis elegans via the receptor SEB-3.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201834}, issn = {1471-2970}, support = {P40 OD010440/OD/NIH HHS/United States ; }, abstract = {Neuropeptide signalling has been implicated in a wide variety of biological processes in diverse organisms, from invertebrates to humans. The Caenorhabditis elegans genome has at least 154 neuropeptide precursor genes, encoding over 300 bioactive peptides. These neuromodulators are thought to largely signal beyond 'wired' chemical/electrical synapse connections, therefore creating a 'wireless' network for neuronal communication. Here, we investigated how behavioural states are affected by neuropeptide signalling through the G protein-coupled receptor SEB-3, which belongs to a bilaterian family of orphan secretin receptors. Using reverse pharmacology, we identified the neuropeptide NLP-49 as a ligand of this evolutionarily conserved neuropeptide receptor. Our findings demonstrate novel roles for NLP-49 and SEB-3 in locomotion, arousal and egg-laying. Specifically, high-content analysis of locomotor behaviour indicates that seb-3 and nlp-49 deletion mutants cause remarkably similar abnormalities in movement dynamics, which are reversed by overexpression of wild-type transgenes. Overexpression of NLP-49 in AVK interneurons leads to heightened locomotor arousal, an effect that is dependent on seb-3. Finally, seb-3 and nlp-49 mutants also show constitutive egg-laying in liquid medium and alter the temporal pattern of egg-laying in similar ways. Together, these results provide in vivo evidence that NLP-49 peptides act through SEB-3 to modulate behaviour, and highlight the importance of neuropeptide signalling in the control of behavioural states.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201833, year = {2018}, author = {White, J}, title = {Clues to basis of exploratory behaviour of the C. elegans snout from head somatotropy.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201833}, issn = {1471-2970}, abstract = {Wave propagation during locomotory movements of Caenorhabditis elegans is constrained to a single dorso/ventral plane. By contrast, the tip of the head (snout) can make rapid exploratory movements in all directions relative to the body axis. These extra degrees of freedom are probably important for animals to seek and identify desirable passages in the interstices of the three-dimensional matrix of soil particles, their usual habitat. The differences in degrees of freedom of movement between snout and body are reflected in the innervation of the musculature. Along the length of the body, the two quadrants of dorsal muscle receive common innervation as do the two quadrants of ventral muscle. By contrast, muscles in the snout have an octagonal arrangement of innervation. It is likely that the exploratory behaviour of the snout is mediated by octant-specific motor and sensory neurons, together with their associated interneurons. The well-defined anatomical structure and neural circuitry of the snout together with behavioural observations should facilitate the implementation of models of the neural basis of exploratory movements, which could lead to an understanding of the basis of this relatively complex behaviour, a behaviour that has similarities to foraging in some vertebrates.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201832, year = {2018}, author = {Larson, SD and Gleeson, P and Brown, AEX}, title = {Connectome to behaviour: modelling Caenorhabditis elegans at cellular resolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1758}, pages = {}, pmid = {30201832}, issn = {1471-2970}, abstract = {It has been 30 years since the 'mind of the worm' was published in Philosophical Transactions B (White et al 1986 Phil. Trans. R. Soc. Lond. B314, 1-340). Predicting Caenorhabditis elegans' behaviour from its wiring diagram has been an enduring challenge since then. This special theme issue of Philosophical Transactions B combines research from neuroscientists, physicists, mathematicians and engineers to discuss advances in neural activity imaging, behaviour quantification and multiscale simulations, and how they are bringing the goal of whole-animal modelling at cellular resolution within reach.This article is part of a discussion meeting issue 'Connectome to behaviour: modelling C. elegans at cellular resolution'.}, } @article {pmid30201728, year = {2018}, author = {Haabeth, OAW and Blake, TR and McKinlay, CJ and Waymouth, RM and Wender, PA and Levy, R}, title = {mRNA vaccination with charge-altering releasable transporters elicits human T cell responses and cures established tumors in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9153-E9161}, pmid = {30201728}, issn = {1091-6490}, support = {R37 CA031841/CA/NCI NIH HHS/United States ; R01 CA031845/CA/NCI NIH HHS/United States ; R35 CA197353/CA/NCI NIH HHS/United States ; R01 CA031841/CA/NCI NIH HHS/United States ; T32 CA196585/CA/NCI NIH HHS/United States ; S10 RR027431/RR/NCRR NIH HHS/United States ; R37 CA031845/CA/NCI NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antigen-Presenting Cells/immunology/pathology ; Antigens, Neoplasm/genetics/*immunology ; Cancer Vaccines/genetics/*immunology/pharmacology ; Cell Line, Tumor ; Female ; HeLa Cells ; Heterografts ; Humans ; *Immunity, Cellular ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Neoplasms, Experimental/genetics/immunology/pathology/*therapy ; RNA, Messenger/genetics/*immunology/pharmacology ; T-Lymphocytes/*immunology/pathology/*transplantation ; *Vaccination ; }, abstract = {In vivo delivery of antigen-encoding mRNA is a promising approach to personalized cancer treatment. The therapeutic efficacy of mRNA vaccines is contingent on safe and efficient gene delivery, biological stability of the mRNA, and the immunological properties of the vaccine. Here we describe the development and evaluation of a versatile and highly efficient mRNA vaccine-delivery system that employs charge-altering releasable transporters (CARTs) to deliver antigen-coding mRNA to antigen-presenting cells (APCs). We demonstrate in human peripheral blood mononuclear cells that CART vaccines can activate a robust antigen-specific immune response against mRNA-encoded viral epitopes. In an established mouse model, we demonstrate that CARTs preferentially target professional APCs in secondary lymphoid organs upon i.v. injections and target local APCs upon s.c. injection. Finally, we show that CARTs coformulated with mRNA and a Toll-like receptor ligand simultaneously transfect and activate target cells to generate an immune response that can treat and cure mice with large, established tumors.}, } @article {pmid30201727, year = {2018}, author = {Wibowo, A and Becker, C and Durr, J and Price, J and Spaepen, S and Hilton, S and Putra, H and Papareddy, R and Saintain, Q and Harvey, S and Bending, GD and Schulze-Lefert, P and Weigel, D and Gutierrez-Marcos, J}, title = {Partial maintenance of organ-specific epigenetic marks during plant asexual reproduction leads to heritable phenotypic variation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9145-E9152}, pmid = {30201727}, issn = {1091-6490}, support = {BB/L025892/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L003023/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N005279/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N00194X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P02601X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/cytology/genetics/*metabolism ; Epigenesis, Genetic/*physiology ; *Plant Somatic Embryogenesis Techniques ; Reproduction, Asexual/*physiology ; }, abstract = {Plants differ from animals in their capability to easily regenerate fertile adult individuals from terminally differentiated cells. This unique developmental plasticity is commonly observed in nature, where many species can reproduce asexually through the ectopic initiation of organogenic or embryogenic developmental programs. While organ-specific epigenetic marks are not passed on during sexual reproduction, the fate of epigenetic marks during asexual reproduction and the implications for clonal progeny remain unclear. Here we report that organ-specific epigenetic imprints in Arabidopsis thaliana can be partially maintained during asexual propagation from somatic cells in which a zygotic program is artificially induced. The altered marks are inherited even over multiple rounds of sexual reproduction, becoming fixed in hybrids and resulting in heritable molecular and physiological phenotypes that depend on the identity of the founder tissue. Consequently, clonal plants display distinct interactions with beneficial and pathogenic microorganisms. Our results demonstrate how novel phenotypic variation in plants can be unlocked through altered inheritance of epigenetic marks upon asexual propagation.}, } @article {pmid30201726, year = {2018}, author = {Giardino Torchia, ML and Ashwell, JD}, title = {Getting MAD at MYC.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9821-9823}, pmid = {30201726}, issn = {1091-6490}, mesh = {Adenine Nucleotides ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors ; Basic-Leucine Zipper Transcription Factors ; *DNA-Binding Proteins ; Mycophenolic Acid/analogs & derivatives ; Proto-Oncogene Proteins c-myc ; Repressor Proteins ; *Transcription Factors ; }, } @article {pmid30201725, year = {2018}, author = {Volden, R and Palmer, T and Byrne, A and Cole, C and Schmitz, RJ and Green, RE and Vollmers, C}, title = {Improving nanopore read accuracy with the R2C2 method enables the sequencing of highly multiplexed full-length single-cell cDNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9726-9731}, pmid = {30201725}, issn = {1091-6490}, support = {R25 GM058903/GM/NIGMS NIH HHS/United States ; T32 HG008345/HG/NHGRI NIH HHS/United States ; T34 GM007910/GM/NIGMS NIH HHS/United States ; }, mesh = {B-Lymphocytes/metabolism ; DNA, Complementary/*genetics ; Gene Expression Profiling/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Nanopores ; Nucleic Acid Amplification Techniques/methods ; RNA Isoforms/genetics ; Reproducibility of Results ; }, abstract = {High-throughput short-read sequencing has revolutionized how transcriptomes are quantified and annotated. However, while Illumina short-read sequencers can be used to analyze entire transcriptomes down to the level of individual splicing events with great accuracy, they fall short of analyzing how these individual events are combined into complete RNA transcript isoforms. Because of this shortfall, long-distance information is required to complement short-read sequencing to analyze transcriptomes on the level of full-length RNA transcript isoforms. While long-read sequencing technology can provide this long-distance information, there are issues with both Pacific Biosciences (PacBio) and Oxford Nanopore Technologies (ONT) long-read sequencing technologies that prevent their widespread adoption. Briefly, PacBio sequencers produce low numbers of reads with high accuracy, while ONT sequencers produce higher numbers of reads with lower accuracy. Here, we introduce and validate a long-read ONT-based sequencing method. At the same cost, our Rolling Circle Amplification to Concatemeric Consensus (R2C2) method generates more accurate reads of full-length RNA transcript isoforms than any other available long-read sequencing method. These reads can then be used to generate isoform-level transcriptomes for both genome annotation and differential expression analysis in bulk or single-cell samples.}, } @article {pmid30201724, year = {2018}, author = {Stehling, O and Jeoung, JH and Freibert, SA and Paul, VD and Bänfer, S and Niggemeyer, B and Rösser, R and Dobbek, H and Lill, R}, title = {Function and crystal structure of the dimeric P-loop ATPase CFD1 coordinating an exposed [4Fe-4S] cluster for transfer to apoproteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9085-E9094}, pmid = {30201724}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Apoproteins/*chemistry/genetics/metabolism ; Catalytic Domain ; Chaetomium/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Fungal Proteins/*chemistry/genetics/metabolism ; GTP-Binding Proteins/*chemistry/genetics/metabolism ; HeLa Cells ; Humans ; Iron Regulatory Protein 1/*chemistry/genetics/metabolism ; Iron-Sulfur Proteins/*chemistry/genetics/metabolism ; }, abstract = {Maturation of iron-sulfur (Fe-S) proteins in eukaryotes requires complex machineries in mitochondria and cytosol. Initially, Fe-S clusters are assembled on dedicated scaffold proteins and then are trafficked to target apoproteins. Within the cytosolic Fe-S protein assembly (CIA) machinery, the conserved P-loop nucleoside triphosphatase Nbp35 performs a scaffold function. In yeast, Nbp35 cooperates with the related Cfd1, which is evolutionary less conserved and is absent in plants. Here, we investigated the potential scaffold function of human CFD1 (NUBP2) in CFD1-depleted HeLa cells by measuring Fe-S enzyme activities or 55Fe incorporation into Fe-S target proteins. We show that CFD1, in complex with NBP35 (NUBP1), performs a crucial role in the maturation of all tested cytosolic and nuclear Fe-S proteins, including essential ones involved in protein translation and DNA maintenance. CFD1 also matures iron regulatory protein 1 and thus is critical for cellular iron homeostasis. To better understand the scaffold function of CFD1-NBP35, we resolved the crystal structure of Chaetomium thermophilum holo-Cfd1 (ctCfd1) at 2.6-Å resolution as a model Cfd1 protein. Importantly, two ctCfd1 monomers coordinate a bridging [4Fe-4S] cluster via two conserved cysteine residues. The surface-exposed topology of the cluster is ideally suited for both de novo assembly and facile transfer to Fe-S apoproteins mediated by other CIA factors. ctCfd1 specifically interacted with ATP, which presumably associates with a pocket near the Cfd1 dimer interface formed by the conserved Walker motif. In contrast, ctNbp35 preferentially bound GTP, implying differential regulation of the two fungal scaffold components during Fe-S cluster assembly and/or release.}, } @article {pmid30201723, year = {2018}, author = {Kaushansky, K}, title = {Hunting for hematopoietic transcriptional networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {9818-9820}, pmid = {30201723}, issn = {1091-6490}, mesh = {Conservation of Natural Resources ; *Gene Regulatory Networks ; *Hematopoietic System ; }, } @article {pmid30201722, year = {2018}, author = {Weaver, VM}, title = {More security may actually make us feel less secure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9649-9651}, pmid = {30201722}, issn = {1091-6490}, } @article {pmid30201721, year = {2018}, author = {Çamdere, GÖ and Carlborg, KK and Koshland, D}, title = {Intermediate step of cohesin's ATPase cycle allows cohesin to entrap DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9732-9737}, pmid = {30201721}, issn = {1091-6490}, support = {R35 GM118189/GM/NIGMS NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/metabolism ; Adenosine Triphosphatases/*metabolism ; Cell Cycle Proteins/*metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA/*metabolism ; DNA Repair ; Saccharomyces cerevisiae/genetics/metabolism ; Schizosaccharomyces/genetics/metabolism ; Schizosaccharomyces pombe Proteins/metabolism ; Translocation, Genetic ; }, abstract = {Cohesin is a four-subunit ATPase in the family of structural maintenance of chromosomes (SMC). Cohesin promotes sister chromatid cohesion, chromosome condensation, DNA repair, and transcription regulation. Cohesin performs these functions as a DNA tether and potentially a DNA-based motor. At least one of its DNA binding activities involves entrapment of DNA within a lumen formed by its subunits. This activity can be reconstituted in vitro by incubating cohesin with DNA, ATP, and cohesin loader. Previously we showed that a mutant form of cohesin (DE-cohesin) possesses the ability to bind and tether DNA in vivo. Using in vitro reconstitution assays, we show that DE-cohesin can form stable complexes with DNA without ATP hydrolysis. We show that wild-type cohesin with ADP aluminum fluoride (cohesinADP/AlFx) can also form stable cohesin-DNA complexes. These results suggest that an intermediate nucleotide state of cohesin, likely cohesinADP-Pi, is capable of initially dissociating one interface between cohesin subunits to allow DNA entry into a cohesin lumen and subsequently interacting with the bound DNA to stabilize DNA entrapment. We also show that cohesinADP/AlFx binding to DNA is enhanced by cohesin loader, suggesting a function for loader other than stimulating the ATPase. Finally, we show that loader remains stably bound to cohesinADP/AlFx after DNA entrapment, potentially revealing a function for loader in tethering the second DNA substrate. These results provide important clues on how SMC complexes like cohesin can function as both DNA tethers and motors.}, } @article {pmid30201720, year = {2018}, author = {Waudby, CA and Wlodarski, T and Karyadi, ME and Cassaignau, AME and Chan, SHS and Wentink, AS and Schmidt-Engler, JM and Camilloni, C and Vendruscolo, M and Cabrita, LD and Christodoulou, J}, title = {Systematic mapping of free energy landscapes of a growing filamin domain during biosynthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9744-9749}, pmid = {30201720}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Filamins/*biosynthesis ; Humans ; Kinetics ; Magnetic Resonance Spectroscopy ; Models, Molecular ; Protein Folding ; Protein Modification, Translational ; Proteostasis Deficiencies/metabolism ; Ribosomes/metabolism ; Tandem Repeat Sequences ; Thermodynamics ; }, abstract = {Cotranslational folding (CTF) is a fundamental molecular process that ensures efficient protein biosynthesis and minimizes the formation of misfolded states. However, the complexity of this process makes it extremely challenging to obtain structural characterizations of CTF pathways. Here, we correlate observations of translationally arrested nascent chains with those of a systematic C-terminal truncation strategy. We create a detailed description of chain length-dependent free energy landscapes associated with folding of the FLN5 filamin domain, in isolation and on the ribosome, and thus, quantify a substantial destabilization of the native structure on the ribosome. We identify and characterize two folding intermediates formed in isolation, including a partially folded intermediate associated with the isomerization of a conserved cis proline residue. The slow folding associated with this process raises the prospect that neighboring unfolded domains might accumulate and misfold during biosynthesis. We develop a simple model to quantify the risk of misfolding in this situation and show that catalysis of folding by peptidyl-prolyl isomerases is sufficient to eliminate this hazard.}, } @article {pmid30201719, year = {2018}, author = {Viegas, J}, title = {Profile of Dana Carroll.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9331-9333}, pmid = {30201719}, issn = {1091-6490}, mesh = {CRISPR-Cas Systems ; Gene Editing/*history/*methods ; History, 20th Century ; History, 21st Century ; Homologous Recombination ; Transcription Activator-Like Effector Nucleases/metabolism ; United States ; Zinc Finger Nucleases/metabolism ; }, } @article {pmid30201718, year = {2018}, author = {Windgassen, TA and Leroux, M and Satyshur, KA and Sandler, SJ and Keck, JL}, title = {Structure-specific DNA replication-fork recognition directs helicase and replication restart activities of the PriA helicase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9075-E9084}, pmid = {30201718}, issn = {1091-6490}, support = {R01 GM098885/GM/NIGMS NIH HHS/United States ; }, mesh = {Crystallography, X-Ray ; DNA Helicases/*chemistry ; *DNA Replication ; DNA, Bacterial/*chemistry ; Escherichia coli/*enzymology ; Escherichia coli Proteins/*chemistry ; *Models, Biological ; Protein Domains ; Protein Structure, Secondary ; Structure-Activity Relationship ; }, abstract = {DNA replication restart, the essential process that reinitiates prematurely terminated genome replication reactions, relies on exquisitely specific recognition of abandoned DNA replication-fork structures. The PriA DNA helicase mediates this process in bacteria through mechanisms that remain poorly defined. We report the crystal structure of a PriA/replication-fork complex, which resolves leading-strand duplex DNA bound to the protein. Interaction with PriA unpairs one end of the DNA and sequesters the 3'-most nucleotide from the nascent leading strand into a conserved protein pocket. Cross-linking studies reveal a surface on the winged-helix domain of PriA that binds to parental duplex DNA. Deleting the winged-helix domain alters PriA's structure-specific DNA unwinding properties and impairs its activity in vivo. Our observations lead to a model in which coordinated parental-, leading-, and lagging-strand DNA binding provide PriA with the structural specificity needed to act on abandoned DNA replication forks.}, } @article {pmid30201717, year = {2018}, author = {Baldwin, M and Mussweiler, T}, title = {The culture of social comparison.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9067-E9074}, pmid = {30201717}, issn = {1091-6490}, mesh = {*Cognition ; *Culture ; *Emotions ; Humans ; *Social Behavior ; *Social Support ; United States ; *Web Browser ; }, abstract = {Social comparison is one of the most ubiquitous features of human social life. This fundamental human tendency to look to others for information about how to think, feel, and behave has provided us with the ability to thrive in a highly complex and interconnected modern social world. Despite its prominent role, however, a detailed understanding of the cultural foundations of social comparison is lacking. The current research aims to fill this gap by showing that two prominent cultural dimensions, tightness-looseness and individualism-collectivism, uniquely explain variation in social-comparison proclivity across individuals, situations, and cultures. We first demonstrate the yet-undocumented link between cultural tightness and comparison proclivity across individuals, and further show that perceptions of ambient tightness and interdependence are uniquely associated with stronger social-comparison tendencies. Next, we show that these associations arise across social settings and can be attributed to properties of the settings themselves, not solely to individual differences. Finally, we show that both tight and collectivistic US states show a propensity to engage in Google searches related to specific social-comparison emotions, but that the tightness-comparison link arises from a unique psychological mechanism. Altogether, these findings show that social comparison-a fundamental aspect of human cognition-is linked to cultural practices based both in prevalence and strength of social norms as well as the tendency to construe the self in relation to others.}, } @article {pmid30201716, year = {2018}, author = {Saul-Gershenz, L and Millar, JG and McElfresh, JS and Williams, NM}, title = {Deceptive signals and behaviors of a cleptoparasitic beetle show local adaptation to different host bee species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9756-9760}, pmid = {30201716}, issn = {1091-6490}, mesh = {Adaptation, Physiological/physiology ; Animals ; Bees/*parasitology ; Coleoptera/*physiology ; Female ; Host-Parasite Interactions/*physiology ; Larva/physiology ; Male ; Sex Attractants/*physiology ; }, abstract = {Chemosensory signals play a key role in species recognition and mate location in both invertebrate and vertebrate species. Closely related species often produce similar but distinct signals by varying the ratios or components in pheromone blends to avoid interference in their communication channels and minimize cross-attraction among congeners. However, exploitation of reproductive signals by predators and parasites also may provide strong selective pressure on signal phenotypes. For example, bolas spiders mimic the pheromones of several moth species to attract their prey, and parasitic blister beetle larvae, known as triungulins, cooperatively produce an olfactory signal that mimics the sex pheromone of their female host bees to attract male bees, as the first step in being transported by their hosts to their nests. In both cases, there is strong selection pressure on the host to discriminate real mates from aggressive mimics and, conversely, on the predator, parasite, or parasitoid to track and locally adapt to the evolving signals of its hosts. Here we show local adaptation of a beetle, Meloe franciscanus (Coleoptera: Meloidae), to the pheromone chemistry and mate location behavior of its hosts, two species of solitary bees in the genus Habropoda We report that Mfranciscanus' deceptive signal is locally host-adapted in its chemical composition and ratio of components, with host bees from each allopatric population preferring the deceptive signals of their sympatric parasite population. Furthermore, in different locales, the triungulin aggregations have adapted their perching height to the height at which local male bees typically patrol for females.}, } @article {pmid30201715, year = {2018}, author = {Martins, D and McKay, G and Sampathkumar, G and Khakimova, M and English, AM and Nguyen, D}, title = {Superoxide dismutase activity confers (p)ppGpp-mediated antibiotic tolerance to stationary-phase Pseudomonas aeruginosa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9797-9802}, pmid = {30201715}, issn = {1091-6490}, support = {MOP102727//CIHR/Canada ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Dose-Response Relationship, Drug ; *Drug Resistance, Multiple, Bacterial ; Gentamicins/pharmacology ; Ligases/metabolism ; Meropenem ; Microbial Sensitivity Tests ; Ofloxacin/pharmacology ; Pseudomonas aeruginosa/*drug effects/enzymology ; Signal Transduction ; Superoxide Dismutase/*metabolism/physiology ; Thienamycins/pharmacology ; }, abstract = {Metabolically quiescent bacteria represent a large proportion of those in natural and host environments, and they are often refractory to antibiotic treatment. Such drug tolerance is also observed in the laboratory during stationary phase, when bacteria face stress and starvation-induced growth arrest. Tolerance requires (p)ppGpp signaling, which mediates the stress and starvation stringent response (SR), but the downstream effectors that confer tolerance are unclear. We previously demonstrated that the SR is linked to increased antioxidant defenses in Pseudomonas aeruginosa We now demonstrate that superoxide dismutase (SOD) activity is a key factor in SR-mediated multidrug tolerance in stationary-phase P. aeruginosa Inactivation of the SR leads to loss of SOD activity and decreased multidrug tolerance during stationary phase. Genetic or chemical complementation of SOD activity of the ΔrelA spoT mutant (ΔSR) is sufficient to restore antibiotic tolerance to WT levels. Remarkably, we observe high membrane permeability and increased drug internalization upon ablation of SOD activity. Combined, our results highlight an unprecedented mode of SR-mediated multidrug tolerance in stationary-phase P. aeruginosa and suggest that inhibition of SOD activity may potentiate current antibiotics.}, } @article {pmid30201714, year = {2018}, author = {Frank, SA}, title = {Measurement invariance explains the universal law of generalization for psychological perception.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9803-9806}, pmid = {30201714}, issn = {1091-6490}, mesh = {Animals ; Discrimination (Psychology) ; *Generalization (Psychology) ; Models, Psychological ; Normal Distribution ; *Perception ; Probability ; }, abstract = {The universal law of generalization describes how animals discriminate between alternative sensory stimuli. On an appropriate perceptual scale, the probability that an organism perceives two stimuli as similar typically declines exponentially with the difference on the perceptual scale. Exceptions often follow a Gaussian probability pattern rather than an exponential pattern. Previous explanations have been based on underlying theoretical frameworks such as information theory, Kolmogorov complexity, or empirical multidimensional scaling. This article shows that the few inevitable invariances that must apply to any reasonable perceptual scale provide a sufficient explanation for the universal exponential law of generalization. In particular, reasonable measurement scales of perception must be invariant to shift by a constant value, which by itself leads to the exponential form. Similarly, reasonable measurement scales of perception must be invariant to multiplication, or stretch, by a constant value, which leads to the conservation of the slope of discrimination with perceptual difference. In some cases, an additional assumption about exchangeability or rotation of underlying perceptual dimensions leads to a Gaussian pattern of discrimination, which can be understood as a special case of the more general exponential form. The three measurement invariances of shift, stretch, and rotation provide a sufficient explanation for the universally observed patterns of perceptual generalization. All of the additional assumptions and language associated with information, complexity, and empirical scaling are superfluous with regard to the broad patterns of perception.}, } @article {pmid30201713, year = {2018}, author = {Elbau, IG and Brücklmeier, B and Uhr, M and Arloth, J and Czamara, D and Spoormaker, VI and Czisch, M and Stephan, KE and Binder, EB and Sämann, PG}, title = {The brain's hemodynamic response function rapidly changes under acute psychosocial stress in association with genetic and endocrine stress response markers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {43}, pages = {E10206-E10215}, pmid = {30201713}, issn = {1091-6490}, mesh = {Brain/physiology ; Cerebrovascular Circulation/physiology ; Endocrine Cells/*physiology ; Genetic Variation/genetics ; Hemodynamics/*physiology ; Humans ; Magnetic Resonance Imaging/methods ; Neurovascular Coupling/*physiology ; Stress, Psychological/*physiopathology ; }, abstract = {Ample evidence links dysregulation of the stress response to the risk for psychiatric disorders. However, we lack an integrated understanding of mechanisms that are adaptive during the acute stress response but potentially pathogenic when dysregulated. One mechanistic link emerging from rodent studies is the interaction between stress effectors and neurovascular coupling, a process that adjusts cerebral blood flow according to local metabolic demands. Here, using task-related fMRI, we show that acute psychosocial stress rapidly impacts the peak latency of the hemodynamic response function (HRF-PL) in temporal, insular, and prefrontal regions in two independent cohorts of healthy humans. These latency effects occurred in the absence of amplitude effects and were moderated by regulatory genetic variants of KCNJ2, a known mediator of the effect of stress on vascular responsivity. Further, hippocampal HRF-PL correlated with both cortisol response and genetic variants that influence the transcriptional response to stress hormones and are associated with risk for major depression. We conclude that acute stress modulates hemodynamic response properties as part of the physiological stress response and suggest that HRF indices could serve as endophenotype of stress-related disorders.}, } @article {pmid30201712, year = {2018}, author = {Kamada, R and Yang, W and Zhang, Y and Patel, MC and Yang, Y and Ouda, R and Dey, A and Wakabayashi, Y and Sakaguchi, K and Fujita, T and Tamura, T and Zhu, J and Ozato, K}, title = {Interferon stimulation creates chromatin marks and establishes transcriptional memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9162-E9171}, pmid = {30201712}, issn = {1091-6490}, support = {ZIA HD008815/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Bone Marrow Cells/cytology/*immunology ; Cell Division/genetics/*immunology ; Chromatin/genetics/immunology ; Epigenesis, Genetic/*immunology ; Histones/genetics/immunology ; *Immunity, Innate ; Interferon-beta/genetics/*immunology ; Macrophages/cytology/*immunology ; Mice ; Mice, Mutant Strains ; RNA Polymerase II/genetics/immunology ; Signal Transduction/genetics/*immunology ; Transcription Factors/genetics/immunology ; Transcription, Genetic/*immunology ; }, abstract = {Epigenetic memory for signal-dependent transcription has remained elusive. So far, the concept of epigenetic memory has been largely limited to cell-autonomous, preprogrammed processes such as development and metabolism. Here we show that IFNβ stimulation creates transcriptional memory in fibroblasts, conferring faster and greater transcription upon restimulation. The memory was inherited through multiple cell divisions and led to improved antiviral protection. Of ∼2,000 IFNβ-stimulated genes (ISGs), about half exhibited memory, which we define as memory ISGs. The rest, designated nonmemory ISGs, did not show memory. Surprisingly, mechanistic analysis showed that IFN memory was not due to enhanced IFN signaling or retention of transcription factors on the ISGs. We demonstrated that this memory was attributed to accelerated recruitment of RNA polymerase II and transcription/chromatin factors, which coincided with acquisition of the histone H3.3 and H3K36me3 chromatin marks on memory ISGs. Similar memory was observed in bone marrow macrophages after IFNγ stimulation, suggesting that IFN stimulation modifies the shape of the innate immune response. Together, external signals can establish epigenetic memory in mammalian cells that imparts lasting adaptive performance upon various somatic cells.}, } @article {pmid30201711, year = {2018}, author = {Sznycer, D and Xygalatas, D and Agey, E and Alami, S and An, XF and Ananyeva, KI and Atkinson, QD and Broitman, BR and Conte, TJ and Flores, C and Fukushima, S and Hitokoto, H and Kharitonov, AN and Onyishi, CN and Onyishi, IE and Romero, PP and Schrock, JM and Snodgrass, JJ and Sugiyama, LS and Takemura, K and Townsend, C and Zhuang, JY and Aktipis, CA and Cronk, L and Cosmides, L and Tooby, J}, title = {Cross-cultural invariances in the architecture of shame.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9702-9707}, pmid = {30201711}, issn = {1091-6490}, mesh = {*Cross-Cultural Comparison ; Culture ; Female ; Humans ; Male ; Residence Characteristics ; *Shame ; Social Behavior ; }, abstract = {Human foragers are obligately group-living, and their high dependence on mutual aid is believed to have characterized our species' social evolution. It was therefore a central adaptive problem for our ancestors to avoid damaging the willingness of other group members to render them assistance. Cognitively, this requires a predictive map of the degree to which others would devalue the individual based on each of various possible acts. With such a map, an individual can avoid socially costly behaviors by anticipating how much audience devaluation a potential action (e.g., stealing) would cause and weigh this against the action's direct payoff (e.g., acquiring). The shame system manifests all of the functional properties required to solve this adaptive problem, with the aversive intensity of shame encoding the social cost. Previous data from three Western(ized) societies indicated that the shame evoked when the individual anticipates committing various acts closely tracks the magnitude of devaluation expressed by audiences in response to those acts. Here we report data supporting the broader claim that shame is a basic part of human biology. We conducted an experiment among 899 participants in 15 small-scale communities scattered around the world. Despite widely varying languages, cultures, and subsistence modes, shame in each community closely tracked the devaluation of local audiences (mean r = +0.84). The fact that the same pattern is encountered in such mutually remote communities suggests that shame's match to audience devaluation is a design feature crafted by selection and not a product of cultural contact or convergent cultural evolution.}, } @article {pmid30201710, year = {2018}, author = {Benej, M and Hong, X and Vibhute, S and Scott, S and Wu, J and Graves, E and Le, QT and Koong, AC and Giaccia, AJ and Yu, B and Chen, CS and Papandreou, I and Denko, NC}, title = {Papaverine and its derivatives radiosensitize solid tumors by inhibiting mitochondrial metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {10756-10761}, pmid = {30201710}, issn = {1091-6490}, support = {S10 OD020006/OD/NIH HHS/United States ; P01 CA067166/CA/NCI NIH HHS/United States ; R01 CA163581/CA/NCI NIH HHS/United States ; R15 CA202605/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; CRISPR-Cas Systems ; Cell Hypoxia/*drug effects/radiation effects ; Cell Proliferation/drug effects/radiation effects ; Female ; Humans ; Lung Neoplasms/drug therapy/pathology/*radiotherapy ; Male ; Mice ; Mice, Inbred C57BL ; Mitochondria/*drug effects/metabolism/radiation effects ; NADH Dehydrogenase/*antagonists & inhibitors/genetics ; Oxygen/*metabolism ; Papaverine/*pharmacology ; Phosphodiesterase Inhibitors/pharmacology ; Radiation Tolerance ; Radiation-Sensitizing Agents/*pharmacology ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Tumor hypoxia reduces the effectiveness of radiation therapy by limiting the biologically effective dose. An acute increase in tumor oxygenation before radiation treatment should therefore significantly improve the tumor cell kill after radiation. Efforts to increase oxygen delivery to the tumor have not shown positive clinical results. Here we show that targeting mitochondrial respiration results in a significant reduction of the tumor cells' demand for oxygen, leading to increased tumor oxygenation and radiation response. We identified an activity of the FDA-approved drug papaverine as an inhibitor of mitochondrial complex I. We also provide genetic evidence that papaverine's complex I inhibition is directly responsible for increased oxygenation and enhanced radiation response. Furthermore, we describe derivatives of papaverine that have the potential to become clinical radiosensitizers with potentially fewer side effects. Importantly, this radiosensitizing strategy will not sensitize well-oxygenated normal tissue, thereby increasing the therapeutic index of radiotherapy.}, } @article {pmid30201709, year = {2018}, author = {Xia, Y and Pu, H and Leak, RK and Shi, Y and Mu, H and Hu, X and Lu, Z and Foley, LM and Hitchens, TK and Dixon, CE and Bennett, MVL and Chen, J}, title = {Tissue plasminogen activator promotes white matter integrity and functional recovery in a murine model of traumatic brain injury.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9230-E9238}, pmid = {30201709}, issn = {1091-6490}, support = {I01 BX003377/BX/BLRD VA/United States ; R01 NS095029/NS/NINDS NIH HHS/United States ; R01 NS108695/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Brain Injuries, Traumatic/*drug therapy/pathology ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Nerve Fibers/drug effects ; Nerve Net/drug effects ; Neuroprotective Agents/*therapeutic use ; Recombinant Proteins ; Tissue Plasminogen Activator/*therapeutic use ; White Matter/*drug effects/pathology ; }, abstract = {Recombinant tissue plasminogen activator (tPA) is a Food and Drug Administration-approved thrombolytic treatment for ischemic stroke. tPA is also naturally expressed in glial and neuronal cells of the brain, where it promotes axon outgrowth and synaptic plasticity. However, there are conflicting reports of harmful versus neuroprotective effects of tPA in acute brain injury models. Furthermore, its impact on white matter integrity in preclinical traumatic brain injury (TBI) has not been thoroughly explored, although white matter disruption is a better predictor of long-term clinical outcomes than focal lesion volumes. Here we show that the absence of endogenous tPA in knockout mice impedes long-term recovery of white matter and neurological function after TBI. tPA-knockout mice exhibited greater asymmetries in forepaw use, poorer sensorimotor balance and coordination, and inferior spatial learning and memory up to 35 d after TBI. White matter damage was also more prominent in tPA knockouts, as shown by diffusion tensor imaging, histological criteria, and electrophysiological assessments of axon conduction properties. Replenishment of tPA through intranasal application of the recombinant protein in tPA-knockout mice enhanced neurological function, the structural and functional integrity of white matter, and postinjury compensatory sprouting in corticofugal projections. tPA also promoted neurite outgrowth in vitro, partly through the epidermal growth factor receptor. Both endogenous and exogenous tPA protected against white matter injury after TBI without increasing intracerebral hemorrhage volumes. These results unveil a previously unappreciated role for tPA in the protection and/or repair of white matter and long-term functional recovery after TBI.}, } @article {pmid30201708, year = {2018}, author = {Jenkins, AC and Karashchuk, P and Zhu, L and Hsu, M}, title = {Predicting human behavior toward members of different social groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9696-9701}, pmid = {30201708}, issn = {1091-6490}, support = {R01 DA043196/DA/NIDA NIH HHS/United States ; R01 MH098023/MH/NIMH NIH HHS/United States ; }, mesh = {Economics, Behavioral ; Female ; Games, Experimental ; Humans ; Male ; Prejudice/psychology ; Psychology, Social ; *Social Behavior ; Social Identification ; Social Perception ; Stereotyping ; }, abstract = {Disparities in outcomes across social groups pervade human societies and are of central interest to the social sciences. How people treat others is known to depend on a multitude of factors (e.g., others' gender, ethnicity, appearance) even when these should be irrelevant. However, despite substantial progress, much remains unknown regarding (i) the set of mechanisms shaping people's behavior toward members of different social groups and (ii) the extent to which these mechanisms can explain the structure of existing societal disparities. Here, we show in a set of experiments the important interplay between social perception and social valuation processes in explaining how people treat members of different social groups. Building on the idea that stereotypes can be organized onto basic, underlying dimensions, we first found using laboratory economic games that quantitative variation in stereotypes about different groups' warmth and competence translated meaningfully into resource allocation behavior toward those groups. Computational modeling further revealed that these effects operated via the interaction of social perception and social valuation processes, with warmth and competence exerting diverging effects on participants' preferences for equitable distributions of resources. This framework successfully predicted behavior toward members of a diverse set of social groups across samples and successfully generalized to predict societal disparities documented in labor and education settings with substantial precision and accuracy. Together, these results highlight a common set of mechanisms linking social group information to social treatment and show how preexisting, societally shared assumptions about different social groups can produce and reinforce societal disparities.}, } @article {pmid30201707, year = {2018}, author = {Yarrington, RM and Verma, S and Schwartz, S and Trautman, JK and Carroll, D}, title = {Nucleosomes inhibit target cleavage by CRISPR-Cas9 in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9351-9358}, pmid = {30201707}, issn = {1091-6490}, support = {R01 GM078571/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/metabolism ; Base Sequence ; Binding Sites/genetics ; CRISPR-Associated Protein 9 ; *CRISPR-Cas Systems ; Chromatin/genetics/metabolism ; DNA, Fungal/genetics/metabolism ; Deoxyribonucleases, Type II Site-Specific/genetics ; Endonucleases/metabolism ; Gene Editing/*methods ; Genomics/*methods ; Nucleosomes/*genetics/metabolism ; Promoter Regions, Genetic/genetics ; Saccharomyces cerevisiae Proteins/genetics ; Zinc Finger Nucleases/metabolism ; }, abstract = {Genome editing with CRISPR-Cas nucleases has been applied successfully to a wide range of cells and organisms. There is, however, considerable variation in the efficiency of cleavage and outcomes at different genomic targets, even within the same cell type. Some of this variability is likely due to the inherent quality of the interaction between the guide RNA and the target sequence, but some may also reflect the relative accessibility of the target. We investigated the influence of chromatin structure, particularly the presence or absence of nucleosomes, on cleavage by the Streptococcus pyogenes Cas9 protein. At multiple target sequences in two promoters in the yeast genome, we find that Cas9 cleavage is strongly inhibited when the DNA target is within a nucleosome. This inhibition is relieved when nucleosomes are depleted. Remarkably, the same is not true of zinc-finger nucleases (ZFNs), which cleave equally well at nucleosome-occupied and nucleosome-depleted sites. These results have implications for the choice of specific targets for genome editing, both in research and in clinical and other practical applications.}, } @article {pmid30201706, year = {2018}, author = {Su, NQ and Li, C and Yang, W}, title = {Describing strong correlation with fractional-spin correction in density functional theory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9678-9683}, pmid = {30201706}, issn = {1091-6490}, support = {R01 GM061870/GM/NIGMS NIH HHS/United States ; }, abstract = {An effective fractional-spin correction is developed to describe static/strong correlation in density functional theory. Combined with the fractional-charge correction from recently developed localized orbital scaling correction (LOSC), a functional, the fractional-spin LOSC (FSLOSC), is proposed. FSLOSC, a correction to commonly used functional approximations, introduces the explicit derivative discontinuity and largely restores the flat-plane behavior of electronic energy at fractional charges and fractional spins. In addition to improving results from conventional functionals for the prediction of ionization potentials, electron affinities, quasiparticle spectra, and reaction barrier heights, FSLOSC properly describes the dissociation of ionic species, single bonds, and multiple bonds without breaking space or spin symmetry and corrects the spurious fractional-charge dissociation of heteroatom molecules of conventional functionals. Thus, FSLOSC demonstrates success in reducing delocalization error and including strong correlation, within low-cost density functional approximation.}, } @article {pmid30201705, year = {2018}, author = {Braun, R and Kath, WL and Iwanaszko, M and Kula-Eversole, E and Abbott, SM and Reid, KJ and Zee, PC and Allada, R}, title = {Universal method for robust detection of circadian state from gene expression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9247-E9256}, pmid = {30201705}, issn = {1091-6490}, mesh = {Biomarkers/blood ; Circadian Clocks/*genetics ; Circadian Rhythm/genetics ; Gene Expression ; Gene Expression Profiling/*methods ; Genes/genetics ; Humans ; *Machine Learning ; Models, Statistical ; Reproducibility of Results ; Sleep ; Transcriptome ; }, abstract = {Circadian clocks play a key role in regulating a vast array of biological processes, with significant implications for human health. Accurate assessment of physiological time using transcriptional biomarkers found in human blood can significantly improve diagnosis of circadian disorders and optimize the delivery time of therapeutic treatments. To be useful, such a test must be accurate, minimally burdensome to the patient, and readily generalizable to new data. A major obstacle in development of gene expression biomarker tests is the diversity of measurement platforms and the inherent variability of the data, often resulting in predictors that perform well in the original datasets but cannot be universally applied to new samples collected in other settings. Here, we introduce TimeSignature, an algorithm that robustly infers circadian time from gene expression. We demonstrate its application in data from three independent studies using distinct microarrays and further validate it against a new set of samples profiled by RNA-sequencing. Our results show that TimeSignature is more accurate and efficient than competing methods, estimating circadian time to within 2 h for the majority of samples. Importantly, we demonstrate that once trained on data from a single study, the resulting predictor can be universally applied to yield highly accurate results in new data from other studies independent of differences in study population, patient protocol, or assay platform without renormalizing the data or retraining. This feature is unique among expression-based predictors and addresses a major challenge in the development of generalizable, clinically useful tests.}, } @article {pmid30201704, year = {2018}, author = {Kritee, K and Nair, D and Zavala-Araiza, D and Proville, J and Rudek, J and Adhya, TK and Loecke, T and Esteves, T and Balireddygari, S and Dava, O and Ram, K and S R, A and Madasamy, M and Dokka, RV and Anandaraj, D and Athiyaman, D and Reddy, M and Ahuja, R and Hamburg, SP}, title = {High nitrous oxide fluxes from rice indicate the need to manage water for both long- and short-term climate impacts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9720-9725}, pmid = {30201704}, issn = {1091-6490}, mesh = {*Climate Change ; Crop Production ; Greenhouse Gases/metabolism ; India ; Nitrous Oxide/*metabolism ; Oryza/*metabolism ; *Water Supply ; }, abstract = {Global rice cultivation is estimated to account for 2.5% of current anthropogenic warming because of emissions of methane (CH4), a short-lived greenhouse gas. This estimate assumes a widespread prevalence of continuous flooding of most rice fields and hence does not include emissions of nitrous oxide (N2O), a long-lived greenhouse gas. Based on the belief that minimizing CH4 from rice cultivation is always climate beneficial, current mitigation policies promote increased use of intermittent flooding. However, results from five intermittently flooded rice farms across three agroecological regions in India indicate that N2O emissions per hectare can be three times higher (33 kg-N2O⋅ha-1⋅season-1) than the maximum previously reported. Correlations between N2O emissions and management parameters suggest that N2O emissions from rice across the Indian subcontinent might be 30-45 times higher under intensified use of intermittent flooding than under continuous flooding. Our data further indicate that comanagement of water with inorganic nitrogen and/or organic matter inputs can decrease climate impacts caused by greenhouse gas emissions up to 90% and nitrogen management might not be central to N2O reduction. An understanding of climate benefits/drawbacks over time of different flooding regimes because of differences in N2O and CH4 emissions can help select the most climate-friendly water management regimes for a given area. Region-specific studies of rice farming practices that map flooding regimes and measure effects of multiple comanaged variables on N2O and CH4 emissions are necessary to determine and minimize the climate impacts of rice cultivation over both the short term and long term.}, } @article {pmid30201512, year = {2019}, author = {Dias Junior, AG and Sampaio, NG and Rehwinkel, J}, title = {A Balancing Act: MDA5 in Antiviral Immunity and Autoinflammation.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {75-85}, doi = {10.1016/j.tim.2018.08.007}, pmid = {30201512}, issn = {1878-4380}, abstract = {Induction of interferons during viral infection is mediated by cellular proteins that recognise viral nucleic acids. MDA5 is one such sensor of virus presence and is activated by RNA. MDA5 is required for immunity against several classes of viruses, including picornaviruses. Recent work showed that mutations in the IFIH1 gene, encoding MDA5, lead to interferon-driven autoinflammatory diseases. Together with observations made in cancer cells, this suggests that MDA5 detects cellular RNAs in addition to viral RNAs. It is therefore important to understand the properties of the RNAs which activate MDA5. New data indicate that RNA length and secondary structure are features sensed by MDA5. We review these developments and discuss how MDA5 strikes a balance between antiviral immunity and autoinflammation.}, } @article {pmid30201511, year = {2019}, author = {Meyer, M and Malherbe, DC and Bukreyev, A}, title = {Can Ebola Virus Vaccines Have Universal Immune Correlates of protection?.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {8-16}, doi = {10.1016/j.tim.2018.08.008}, pmid = {30201511}, issn = {1878-4380}, support = {R01 AI102887/AI/NIAID NIH HHS/United States ; }, abstract = {Testing vaccine efficacy against the highly lethal Ebola virus (EBOV) in humans is almost impossible due to obvious ethical reasons and the sporadic nature of outbreaks. For such situations, the 'animal rule' was established, requiring the product be tested in animal models, expected to predict the response observed in humans. For vaccines, this testing aims to identify immune correlates of protection, such as antibody or cell-mediated responses. In the wake of the 2013-2016 EBOV epidemic, and despite advancement of promising candidates into clinical trials, protective correlates remain ambiguous. In the hope of identifying a reliable correlate by comparing preclinical and clinical trial data on immune responses to vaccination, we conclude that correlates are not universal for all EBOV vaccines.}, } @article {pmid30201437, year = {2018}, author = {Wadsworth, WG}, title = {A perspective on SOAL, a stochastic model of neuronal outgrowth.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {92-101}, doi = {10.1016/j.ydbio.2018.09.007}, pmid = {30201437}, issn = {1095-564X}, mesh = {Cell Differentiation/physiology ; Models, Biological ; Models, Theoretical ; Nerve Growth Factors/genetics/metabolism ; Neurites/metabolism ; Neuronal Outgrowth/*genetics/*physiology ; Neurons/*metabolism/physiology ; Stochastic Processes ; }, abstract = {A functional nervous system requires neuronal connections to be made in a highly detailed and stereotypic manner. During development, neurons extend processes that can branch, travel in different directions, and form elaborate patterns. These patterns are essential for forming proper connections. Patterns of outgrowth are produced by complex molecular events that cause a fluid membrane to move. The collective impact of dynamic fluctuating events at the microscale cause the patterns of outgrowth observed at the macroscale. Patterning is genetically controlled, but the effects genes have on membrane movement and patterning are not well understood. To better understand how genes control outgrowth patterns, I propose a statistically-oriented asymmetric localization (SOAL) model. This model is based on the theory that receptor-mediated outgrowth activity is stochastically oriented and when the system is at equilibrium there is an equal probability of outgrowth being oriented in any direction. This concept allows a statistical mechanics approach that can correlate the microscale events of outgrowth to the observed macroscale patterns. Proof-of-concept experiments suggest this approach can be used to study the effect genes have on outgrowth patterns. The SOAL model also provides a new theoretical framework for conceptualizing guidance. According to the model, outgrowth activity becomes asymmetrically localized to the neuron's surface in a statistically dependent manner. Extracellular cues regulate the probability of outgrowth along the surface and the orientation of outgrowth fluctuates across the surface over time. This creates a directional bias that allows the growth cone to navigate in reference to the composition of extracellular cues.}, } @article {pmid30201427, year = {2018}, author = {Chen, and Braun, EL and Forthman, M and Kimball, RT and Zhang, Z}, title = {A simple strategy for recovering ultraconserved elements, exons, and introns from low coverage shotgun sequencing of museum specimens: Placement of the partridge genus Tropicoperdix within the galliformes.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {304-314}, doi = {10.1016/j.ympev.2018.09.005}, pmid = {30201427}, issn = {1095-9513}, abstract = {Next-generation DNA sequencing (NGS) offers a promising way to obtain massive numbers of orthologous loci to understand phylogenetic relationships among organisms. Of particular interest are old museum specimens and other samples with degraded DNA, where traditional sequencing methods have proven to be challenging. Low coverage shotgun sequencing and sequence capture are two widely used NGS approaches for degraded DNA. Sequence capture can yield sequence data for large numbers of orthologous loci, but it can only be used to sequence genomic regions near conserved sequences that can be used as probes. Low coverage shotgun sequencing has the potential to yield different data types throughout the genome. However, many studies using this method have often generated mitochondrial sequences, and few nuclear sequences, suggesting orthologous nuclear sequences are likely harder to recover. To determine the phylogenetic position of the galliform genus Tropicoperdix, whose phylogenetic position is currently uncertain, we explored two strategies to maximize data extraction from low coverage shotgun sequencing from approximately 100-year-old museum specimens from two species of Tropicoperdix. One approach, a simple read mapping strategy, outperformed the other (a reduced complexity assembly approach), and allowed us to obtain a large number of ultraconserved element (UCE) loci, relatively conserved exons, more variable introns, as well as mitochondrial genomes. Additionally, we demonstrated some simple approaches to explore possible artifacts that may result from the use of degraded DNA. Our data placed Tropicoperdix within a clade that includes many taxa characterized with ornamental eyespots (peafowl, argus pheasants, and peacock pheasants), and established relationships among species within the genus. Therefore, our study demonstrated that low coverage shotgun sequencing can easily be leveraged to yield substantial amounts and varying types of data, which opens the door for many research questions that might require information from different data types from museum specimens.}, } @article {pmid30201426, year = {2018}, author = {González Marín, A and Olave, M and Avila, LJ and Sites, JW and Morando, M}, title = {Evidence of body size and shape stasis driven by selection in Patagonian lizards of the Phymaturus patagonicus clade (Squamata: Liolaemini).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {226-241}, doi = {10.1016/j.ympev.2018.08.019}, pmid = {30201426}, issn = {1095-9513}, abstract = {During the speciation process sibling lineages accumulate differences in time (e.g. genetic, morphological, and/or ecological). Phenotypic traits such as size or shape, however, could experience rapid changes or show stasis depending on their role in survival and reproduction. The clade Phymaturus patagonicus includes 26 species characterized by a conservative morphology, and all inhabit rock crevice microhabitats in arid environments. In this study we quantify levels of morphological divergence (size and shape) among the multiple species relative to interspecific molecular divergence, and show that most species have not diverged significantly in size and/or shape to permit unambiguous species diagnosis with morphological data alone. The influence of stabilizing selection for an adaptive optimum in body size and head shape was detected for 13 of the 16 variables analyzed in an Ornstein-Uhlenbeck model. The strict dependence of these species to rock-crevice microenvironments likely explains the observed morphological stasis across the many species of the Phymaturus patagonicus group.}, } @article {pmid30201278, year = {2018}, author = {Santos, HJ and Makiuchi, T and Nozaki, T}, title = {Reinventing an Organelle: The Reduced Mitochondrion in Parasitic Protists.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1038-1055}, doi = {10.1016/j.pt.2018.08.008}, pmid = {30201278}, issn = {1471-5007}, abstract = {Mitochondria originated from the endosymbiotic event commencing from the engulfment of an ancestral α-proteobacterium by the first eukaryotic ancestor. Establishment of niches has led to various adaptations among eukaryotes. In anaerobic parasitic protists, the mitochondria have undergone modifications by combining features shared from the aerobic mitochondria with lineage-specific components and mechanisms; a diversified class of organelles emerged and are generally called mitochondrion-related organelles (MROs). In this review we summarize and discuss the recent advances in the knowledge of MROs from parasitic protists, particularly the themes such as metabolic functions, contribution to parasitism, dynamics, protein targeting, and novel lineage- specific proteins, with emphasis on the diversity among these organelles.}, } @article {pmid30201119, year = {2018}, author = {Conde-Valverde, M and Quam, R and Martínez, I and Arsuaga, JL and Daura, J and Sanz, M and Zilhão, J}, title = {The bony labyrinth in the Aroeira 3 Middle Pleistocene cranium.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {105-116}, doi = {10.1016/j.jhevol.2018.08.003}, pmid = {30201119}, issn = {1095-8606}, abstract = {The discovery of a partial cranium at the site of Aroeira (Portugal) dating to 389-436 ka augments the current sample of Middle Pleistocene European crania and makes this specimen penecontemporaneous with the fossils from the geographically close Atapuerca Sima de los Huesos (SH) and Arago sites. A recent study of the cranium documented a unique combination of primitive and derived features. The Aroeira 3 cranium preserves the right temporal bone, including the petrosal portion. Virtual reconstruction of the bony labyrinth from μCT scans provides an opportunity to examine its morphology. A series of standard linear and angular measures of the semicircular canals and cochlea in Aroeira 3 were compared with other fossil hominins and recent humans. Our analysis has revealed the absence of derived Neandertal features in Aroeira 3. In particular, the specimen lacks both the derived canal proportions and the low position of the posterior canal, two of the most diagnostic features of the Neandertal bony labyrinth, and Aroeira 3 is more primitive in these features than the Atapuerca (SH) sample. One potentially derived feature (low shape index of the cochlear basal turn) is shared between Aroeira 3 and the Atapuerca (SH) hominins, but is absent in Neandertals. The results of our study provide new insights into Middle Pleistocene population dynamics close to the origin of the Neandertal clade. In particular, the contrasting inner ear morphology between Aroeira 3 and the Atapuerca (SH) hominins suggests a degree of demographic isolation, despite the close geographic proximity and similar age of these two sites.}, } @article {pmid30201054, year = {2018}, author = {Noordraven, EL and Wierdsma, AI and Blanken, P and Bloemendaal, AFT and Mulder, CL}, title = {Medical and social costs after using financial incentives to improve medication adherence: results of a 1 year randomised controlled trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {655}, pmid = {30201054}, issn = {1756-0500}, support = {R43 TR002350/TR/NCATS NIH HHS/United States ; }, mesh = {Antipsychotic Agents/*administration & dosage ; Cost-Benefit Analysis ; Drug Costs ; *Financing, Personal ; *Health Care Costs ; Humans ; *Medication Adherence ; *Motivation ; *Psychotic Disorders/drug therapy/economics ; }, abstract = {OBJECTIVE: Offering a financial incentive ('Money for Medication') is effective in improving adherence to treatment with depot antipsychotic medications. We investigated the cost-effectiveness in terms of medical costs and judicial expenses of using financial incentives to improve adherence. The effects of financial incentives on depot medication adherence were evaluated in a randomised controlled trial. Patients in the intervention group received €30 a month over 12 months if antipsychotic depot medication was accepted. The control group received mental health care as usual. For 133 patients outcomes were calculated based on self-reported service use and delinquent behaviour and expressed as standard unit costs to value resource use.

RESULTS: The financial incentive resulted in higher average costs related to mental health care (€449.6 versus €355.7). and lower medical costs related to other healthcare services (€52.0 versus €78.4). Relevant differences in social costs related to delinquent behaviour were not found. Although wide confidence intervals indicate uncertainty, incremental cost-effectiveness ratio's (ICER) indicate that it costs €2080 for achieving a 20% increase in adherence or €3332 for achieving over 80% adherence. In sum, offering money as financial incentive for increasing compliance did not lead to an overall cost reduction as compared to care as usual. Trial registration NTR2350, 01 June 2010.}, } @article {pmid30201048, year = {2018}, author = {Bender, JM and Li, F and Adisetiyo, H and Lee, D and Zabih, S and Hung, L and Wilkinson, TA and Pannaraj, PS and She, RC and Bard, JD and Tobin, NH and Aldrovandi, GM}, title = {Quantification of variation and the impact of biomass in targeted 16S rRNA gene sequencing studies.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {155}, pmid = {30201048}, issn = {2049-2618}, support = {K12 HD052954/HD/NICHD NIH HHS/United States ; UM1 AI068632/AI/NIAID NIH HHS/United States ; UM1 AI068616/AI/NIAID NIH HHS/United States ; UM1 AI106716/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Recent advances in sequencing technologies and bioinformatics tools have allowed for large-scale microbiome studies that are rapidly advancing medical research. However, small changes in technique or analysis can significantly alter the results and lead to conflicting findings. Quantifying the technical versus biological variation expected in targeted 16S rRNA gene sequencing studies and how this variation changes with input biomass is critical to guide meaningful interpretation of the current literature and plan future research.

RESULTS: Data were compiled from 469 sequencing libraries across 19 separate targeted 16S rRNA gene sequencing runs over a 2.5-year time period. Following removal of contaminant sequences identified from negative controls, 244 samples retained sufficient reads for further analysis. Coefficients of variation for intra- and inter-assay variation from repeated measurements of a bacterial mock community ranged from 8.7 to 37.6% (intra) and 15.6 to 80.5% (inter) for all but one genus of bacteria whose relative abundance was greater than 1%. Intra- versus inter-assay Bray-Curtis pairwise distances for a single stool sample were 0.11 versus 0.31, whereas intra-assay variation from repeat stool samples from the same donor was greater at 0.38 (Wilcoxon p = 0.001). A dilution series of the bacterial mock community was used to assess the effect of input biomass on variability. Pairwise distances increased with more dilute samples, and estimates of relative abundance became unreliable below approximately 100 copies of the 16S rRNA gene per microliter. Using this data, we created a prediction model to estimate the expected variation in microbiome measurements for given input biomass and relative abundance values.

CONCLUSIONS: Well-controlled microbiome studies are sufficiently robust to capture small biological effects and can achieve levels of variability consistent with clinical assays. Relative abundance is negatively associated with measures of variability and has a stronger effect on variability than does absolute biomass, suggesting that it is feasible to detect differences in bacterial populations in very low-biomass samples. Further, by quantifying the effect of biomass and relative abundance on compositional variability, we developed a tool for defining the expected variance in a given microbiome study.}, } @article {pmid30201047, year = {2018}, author = {Dorji, T and Gyeltshen, K and Pongpirul, K}, title = {Rational use of paracetamol among out-patients in a Bhutanese district hospital bordering India: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {660}, pmid = {30201047}, issn = {1756-0500}, mesh = {Acetaminophen/*therapeutic use ; Adolescent ; Adult ; Aged ; Analgesics, Non-Narcotic/*therapeutic use ; Bhutan ; Cross-Sectional Studies ; Female ; *Hospitals, District ; Humans ; Male ; Middle Aged ; Outpatients ; Practice Patterns, Physicians'/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: Paracetamol or acetaminophen is a weak analgesic commonly used worldwide and in Bhutan. It is available across all levels of Bhutan's health care system and for purchase without prescription. Little is known, however, about patterns of paracetamol use in Bhutan. This study aimed to assess what the Bhutanese population knows about the indications for use of paracetamol, safe use, and common patterns of usage (frequency, dosage). These questions were studied among Bhutanese living in Phuentsholing, a large commercial town at Bhutan-India border.

RESULTS: Among 441 participants, most (72.1%) reported having used paracetamol in the past 1 year. The mean knowledge score was 57.6%; only 30 participants (6.8%) had what was characterized as "good knowledge." Level of knowledge was positively associated with level of education (p = 0.031). Less than half (41.3%) had a "good attitude" towards use of paracetamol. In practice, few (4.8%) knew the correct dose, including about one in ten who reported exceeding the recommended therapeutic dose. Most knew about side effects (61.2%) and possible allergic reactions (77.3%). Many participants (47.9%) acknowledged that the self-use of paracetamol may not reduce the number of hospital visits.}, } @article {pmid30201042, year = {2018}, author = {Kerie, S and Tilahun, A and Mandesh, A}, title = {Triage skill and associated factors among emergency nurses in Addis Ababa, Ethiopia 2017: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {658}, pmid = {30201042}, issn = {1756-0500}, mesh = {Adult ; *Clinical Competence ; Cross-Sectional Studies ; Emergency Service, Hospital ; Ethiopia ; Female ; Humans ; Indonesia ; Male ; Nursing Staff, Hospital/*standards ; *Triage ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to assess levels of triage skill and associated factors among emergency nurses in Addis Ababa, Ethiopia, 2017.

RESULTS: Above half of the participants (52.9%) had a moderate level of triage skill. A strong positive relationship was found between nurses' level of triage knowledge and skill (r = .68, p .01). Knowledge about triage, educational level and training experience had a significant relationship with triage skill with (B = 1.09, CI (1.41, 1.77), p = .002), (B = - 19.96, CI (- 30.208, - 9.715), p = .001), (B = .55, CI .16, .94), p = .006) respectively. This study revealed that most triage nurses had a moderate level of skills. Therefore, the ministry of health and hospitals should provide training and education to improve triage skill.}, } @article {pmid30201041, year = {2018}, author = {Iroh Tam, PY and Hernandez-Alvarado, N and Schleiss, MR and Yi, AJ and Hassan-Hanga, F and Onuchukwu, C and Umoru, D and Obaro, SK}, title = {Detection of Streptococcus pneumoniae from culture-negative dried blood spots by real-time PCR in Nigerian children with acute febrile illness.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {657}, pmid = {30201041}, issn = {1756-0500}, support = {R01 HD044864/HD/NICHD NIH HHS/United States ; Robert Austrian Grant//ISPPD/ ; OPP1034619//Bill and Melinda Gates Foundation/ ; AI097493//National Institutes of Health/ ; HD044864//National Institutes of Health (US)/ ; R01 AI097493/AI/NIAID NIH HHS/United States ; }, mesh = {Belgium ; Child, Preschool ; Fever/*diagnosis ; Humans ; Infant ; Nigeria ; *Real-Time Polymerase Chain Reaction ; Sensitivity and Specificity ; Streptococcus pneumoniae/*genetics/isolation & purification ; }, abstract = {OBJECTIVES: Acute febrile illness is a common cause of hospital admission, and its associated infectious causes, of which a key bacterial causative agent is Streptococcus pneumoniae, contribute to substantial morbidity and mortality. We sought to evaluate the utility of real-time (rt)-PCR on dried blood spots (DBS) for diagnosis of S. pneumoniae in acute febrile illness among children presenting to hospitals in Nigeria. We previously described preliminary results in a sample of 537 patients. Here we present data from a larger collection of 1038 patients.

RESULTS: Using rt-PCR for Streptococcus pneumoniae on 1038 dried blood spots from children prospectively enrolled with acute febrile illness, including 79 healthy controls, we detected pneumococcal DNA in nine of 15 blood culture-positive specimens, one culture-negative specimen from a high-risk group, a culture-confirmed non-pneumococcal specimen and a healthy control. Six culture-positive isolates (40%) were negative. Sensitivity was 60%, specificity 99.7%, positive predictive value 75% and negative predictive value 99.4%. Rt-PCR of DBS has limited sensitivity in blood specimens from acute febrile illness in children.}, } @article {pmid30201034, year = {2018}, author = {Valido, EM and Laksanawati, IS and Utarini, A}, title = {Acceptability of the dengue vaccination among parents in urban poor communities of Quezon City, Philippines before and after vaccine suspension.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {661}, pmid = {30201034}, issn = {1756-0500}, mesh = {Child ; Dengue/*prevention & control ; *Dengue Vaccines ; Health Knowledge, Attitudes, Practice ; Humans ; *Parents ; *Patient Acceptance of Health Care ; Philippines ; Vaccination ; Vaccines ; }, abstract = {OBJECTIVE: The study aims to illustrate the acceptability of the dengue vaccine before and after the dengue vaccination suspension in urban poor communities in Quezon City, Philippines.

RESULTS: There were 12 interviews conducted in November 2017 and 5 focus group discussions in January 2018, a month after vaccine program suspension with 41 participants. All participants were selected through purposive criterion sampling. Thematic analysis showed acceptability of the dengue vaccine was associated with parental experience with vaccination and dengue, trust in public health institutions and communication received by parents. Post-dengue vaccination suspension triangulation indicated that the parents regretted the experience, trust to public institutions was eroded and the communication strategy was deemed inadequate. This led to low vaccine acceptability post-vaccine suspension.}, } @article {pmid30201033, year = {2018}, author = {Anokye, R and Acheampong, E and Budu-Ainooson, A and Edusei, AK and Okyere, P and Dogbe, J and Nadutey, A}, title = {Socio-demographic determinants of childhood immunization incompletion in Koforidua, Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {656}, pmid = {30201033}, issn = {1756-0500}, mesh = {Child ; Child, Preschool ; Cross-Sectional Studies ; Demography ; Female ; Ghana ; Humans ; *Immunization ; Immunization Programs ; Infant ; Infant, Newborn ; Retrospective Studies ; *Socioeconomic Factors ; }, abstract = {OBJECTIVE: Immunization saves more than 3 million lives worldwide each year, and it saves millions from suffering illness and lifelong disability. The study sought to assess the socio-demographic factors that influence childhood immunization incompletion. A cross-sectional descriptive design was employed for the study conducted at the Child Welfare Clinic in the Regional Hospital, Koforidua. A total of 280 caregivers/mothers who have children aged between 0 and 59 months were included in this study. Data were entered and analyzed using SPSS.

RESULTS: The study found that being divorced (p = 0.048) and working part-time (p = 0.049) has a significant and positive association with immunization incompletion. Women who were divorced [AOR (95% CI) 3.01 (1.59-58.2)] were 3 times less likely to complete immunization than those who were cohabiting, married and widowed taken into account the effect due to all the additional confounder variables included in the analysis. Women who were working part-time were 2.28 times less likely to complete immunization schedule than those working full-time; [AOR (95% CI) 2.28 (1.031-9.11)]. This study has documented socio-demographic factors influencing childhood immunization incompletion in the Regional Hospital, Koforidua. The Ministry of Health should, therefore, put in measures like public education to encourage mothers to complete each immunization schedule.}, } @article {pmid30201028, year = {2018}, author = {Pusparini, N and Waturangi, DE and Usia, T and Nikastri, E}, title = {Genetic diversity of Escherichia coli isolated from ice cube production sites.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {659}, pmid = {30201028}, issn = {1756-0500}, mesh = {DNA Fingerprinting ; DNA, Bacterial ; Escherichia coli/*genetics/isolation & purification ; *Genetic Variation ; *Ice ; Indonesia ; Phylogeny ; }, abstract = {OBJECTIVE: The prevalence of Escherichia coli including from ice cubes in Indonesia is quite high. Unfortunately, little is known about the genetic diversity of E. coli from ice cube production site. Genotypic variation in E. coli populations is a major barrier to control public health risk associated with foodborne pathogen. The aims of this study were to analyze the genotypic diversity of E. coli strains isolated from various samples in order to determine the genetic relationship between those strains. This study is also important to understand the occurrence, prevalence and profile picture of different pathogenic E. coli in various sources which potentially cause disease.

RESULTS: Enterobacterial repetitive intergenic consensus (ERIC) and repetitive extragenic palindromic polymerase chain reaction (REP-PCR) dendrogram showed high genetic diversity of 120 E. coli isolates in majority of sampling sites. DNA fingerprint patterns showed 26 and 21 clusters with 11 and 3 fingerprints individual lineages for ERIC and REP-PCR respectively. There was no correlation observed between phylogenetic relationship and virulence genes. The result indicated a variation of E. coli isolates in ice cube manufacturers. ERIC-PCR method is more discriminative compared with REP-PCR to analyze the genetic diversity of E. coli from ice cubes production sites.}, } @article {pmid30201027, year = {2018}, author = {Vollrath, ME and Torgersen, S and Torgersen, L}, title = {Associations of children's Big Five personality with eating behaviors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {654}, pmid = {30201027}, issn = {1756-0500}, mesh = {Adult ; Child ; Cohort Studies ; Cross-Sectional Studies ; Eating ; *Feeding Behavior ; Female ; Humans ; Male ; Norway ; *Personality ; Pilot Projects ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Our aim is to examine the associations of the Big Five personality factors with eating behaviors in children using a cross-sectional study in 1543 randomly Norwegian 7-12 year olds.

RESULTS: Mothers rated the hierarchical personality inventory for children, and the child eating behaviour questionnaire to describe her child. Personality and eating behaviors were substantially associated in bivariate correlations and multivariate analyses of variance. The strongest predictors of eating behaviors were neuroticism, followed by agreeableness and conscientiousness. Neuroticism correlated the highest with slow eating, emotional undereating, food responsiveness, and emotional overeating, and showed minor associations with satiety responsiveness, and fussiness. Neuroticism was not associated with enjoyment of food. Agreeableness was associated with low fussiness, low emotional undereating, low food responsiveness and low emotional overeating, conscientiousness was associated with low satiety responsiveness, and food responsiveness, and extraversion and imagination were associated with high enjoyment of food.}, } @article {pmid30200940, year = {2018}, author = {Zhu, M and Cortese, GP and Waites, CL}, title = {Parkinson's disease-linked Parkin mutations impair glutamatergic signaling in hippocampal neurons.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {100}, pmid = {30200940}, issn = {1741-7007}, support = {R01 NS080967/NS/NINDS NIH HHS/United States ; }, abstract = {BACKGROUND: Parkinson's disease (PD)-associated E3 ubiquitin ligase Parkin is enriched at glutamatergic synapses, where it ubiquitinates multiple substrates, suggesting that its mutation/loss-of-function could contribute to the etiology of PD by disrupting excitatory neurotransmission. Here, we evaluate the impact of four common PD-associated Parkin point mutations (T240M, R275W, R334C, G430D) on glutamatergic synaptic function in hippocampal neurons.

RESULTS: We find that expression of these point mutants in cultured hippocampal neurons from Parkin-deficient and Parkin-null backgrounds alters NMDA and AMPA receptor-mediated currents and cell-surface levels and prevents the induction of long-term depression. Mechanistically, we demonstrate that Parkin regulates NMDA receptor trafficking through its ubiquitination of GluN1, and that all four mutants are impaired in this ubiquitinating activity. Furthermore, Parkin regulates synaptic AMPA receptor trafficking via its binding and retention of the postsynaptic scaffold Homer1, and all mutants are similarly impaired in this capacity.

CONCLUSION: Our findings demonstrate that pathogenic Parkin mutations disrupt glutamatergic synaptic transmission in hippocampal neurons by impeding NMDA and AMPA receptor trafficking. Such effects may contribute to the pathophysiology of PD in PARK2 patients.}, } @article {pmid30200936, year = {2018}, author = {Verschut, TA and Hambäck, PA}, title = {A random survival forest illustrates the importance of natural enemies compared to host plant quality on leaf beetle survival rates.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {33}, pmid = {30200936}, issn = {1472-6785}, support = {BS2015-0063//Royal Swedish Academy of Sciences/International ; VR-2009-4943//Vetenskapsrådet/International ; VR-2012-3578//Vetenskapsrådet/International ; }, abstract = {BACKGROUND: Wetlands are habitats where variation in soil moisture content and associated environmental conditions can strongly affect the survival of herbivorous insects by changing host plant quality and natural enemy densities. In this study, we combined natural enemy exclusion experiments with random survival forest analyses to study the importance of local variation in host plant quality and predation by natural enemies on the egg and larval survival of the leaf beetle Galerucella sagittariae along a soil moisture gradient.

RESULTS: Our results showed that the exclusion of natural enemies substantially increased the survival probability of G. sagittariae eggs and larvae. Interestingly, the egg survival probability decreased with soil moisture content, while the larval survival probability instead increased with soil moisture content. For both the egg and larval survival, we found that host plant height, the number of eggs or larvae, and vegetation height explained more of the variation than the soil moisture gradient by itself. Moreover, host plant quality related variables, such as leaf nitrogen, carbon and phosphorus content did not influence the survival of G. sagittariae eggs and larvae.

CONCLUSION: Our results suggest that the soil moisture content is not an overarching factor that determines the interplay between factors related to host plant quality and factors relating to natural enemies on the survival of G. sagittariae in different microhabitats. Moreover, the natural enemy exclusion experiments and the random survival forest analysis suggest that natural enemies have a stronger indirect impact on the survival of G. sagittariae offspring than host plant quality.}, } @article {pmid30200934, year = {2018}, author = {Behm, JE and Waite, BR and Hsieh, ST and Helmus, MR}, title = {Benefits and limitations of three-dimensional printing technology for ecological research.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {32}, pmid = {30200934}, issn = {1472-6785}, support = {858.14.040//Nederlands Instituut voor Onderzoek van de Gezondheidszorg (NL)/International ; }, abstract = {BACKGROUND: Ecological research often involves sampling and manipulating non-model organisms that reside in heterogeneous environments. As such, ecologists often adapt techniques and ideas from industry and other scientific fields to design and build equipment, tools, and experimental contraptions custom-made for the ecological systems under study. Three-dimensional (3D) printing provides a way to rapidly produce identical and novel objects that could be used in ecological studies, yet ecologists have been slow to adopt this new technology. Here, we provide ecologists with an introduction to 3D printing.

RESULTS: First, we give an overview of the ecological research areas in which 3D printing is predicted to be the most impactful and review current studies that have already used 3D printed objects. We then outline a methodological workflow for integrating 3D printing into an ecological research program and give a detailed example of a successful implementation of our 3D printing workflow for 3D printed models of the brown anole, Anolis sagrei, for a field predation study. After testing two print media in the field, we show that the models printed from the less expensive and more sustainable material (blend of 70% plastic and 30% recycled wood fiber) were just as durable and had equal predator attack rates as the more expensive material (100% virgin plastic).

CONCLUSIONS: Overall, 3D printing can provide time and cost savings to ecologists, and with recent advances in less toxic, biodegradable, and recyclable print materials, ecologists can choose to minimize social and environmental impacts associated with 3D printing. The main hurdles for implementing 3D printing-availability of resources like printers, scanners, and software, as well as reaching proficiency in using 3D image software-may be easier to overcome at institutions with digital imaging centers run by knowledgeable staff. As with any new technology, the benefits of 3D printing are specific to a particular project, and ecologists must consider the investments of developing usable 3D materials for research versus other methods of generating those materials.}, } @article {pmid30200901, year = {2018}, author = {Dessì, D and Cirrone, J and Recupero, DR and Shasha, D}, title = {SuperNoder: a tool to discover over-represented modular structures in networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {318}, pmid = {30200901}, issn = {1471-2105}, mesh = {*Algorithms ; Computational Biology/*methods ; Humans ; *Metabolic Networks and Pathways ; *Protein Interaction Maps ; *Software ; }, abstract = {BACKGROUND: Networks whose nodes have labels can seem complex. Fortunately, many have substructures that occur often ("motifs"). A societal example of a motif might be a household. Replacing such motifs by named supernodes reduces the complexity of the network and can bring out insightful features. Doing so repeatedly may give hints about higher level structures of the network. We call this recursive process Recursive Supernode Extraction.

RESULTS: This paper describes algorithms and a tool to discover disjoint (i.e. non-overlapping) motifs in a network, replacing those motifs by new nodes, and then recursing. We show applications in food-web and protein-protein interaction (PPI) networks where our methods reduce the complexity of the network and yield insights.

CONCLUSIONS: SuperNoder is a web-based and standalone tool which enables the simplification of big graphs based on the reduction of high frequency motifs. It applies various strategies for identifying disjoint motifs with the goal of enhancing the understandability of networks.}, } @article {pmid30200892, year = {2018}, author = {van de Vossenberg, BTLH and Brankovics, B and Nguyen, HDT and van Gent-Pelzer, MPE and Smith, D and Dadej, K and Przetakiewicz, J and Kreuze, JF and Boerma, M and van Leeuwen, GCM and André Lévesque, C and van der Lee, TAJ}, title = {The linear mitochondrial genome of the quarantine chytrid Synchytrium endobioticum; insights into the evolution and recent history of an obligate biotrophic plant pathogen.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {136}, pmid = {30200892}, issn = {1471-2148}, support = {Roots, Tubers and Bananas (RTB)//CGIAR/International ; 1406-056//Topsector Tuinbouw & Uitgangsmaterialen/International ; J-000985//Agriculture and Agri-Food Canada/International ; }, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Chytridiomycota/*genetics/pathogenicity ; DNA, Mitochondrial/genetics ; Europe ; Genetic Variation ; *Genome, Mitochondrial ; Haplotypes/genetics ; Molecular Sequence Annotation ; Phylogeny ; Plant Diseases/microbiology ; Plants/*microbiology ; Quarantine ; Reproducibility of Results ; Species Specificity ; Virulence/genetics ; }, abstract = {BACKGROUND: Chytridiomycota species (chytrids) belong to a basal lineage in the fungal kingdom. Inhabiting terrestrial and aquatic environments, most are free-living saprophytes but several species cause important diseases: e.g. Batrachochytrium dendrobatidis, responsible for worldwide amphibian decline; and Synchytrium endobioticum, causing potato wart disease. S. endobioticum has an obligate biotrophic lifestyle and isolates can be further characterized as pathotypes based on their virulence on a differential set of potato cultivars. Quarantine measures have been implemented globally to control the disease and prevent its spread. We used a comparative approach using chytrid mitogenomes to determine taxonomical relationships and to gain insights into the evolution and recent history of introductions of this plant pathogen.

RESULTS: We assembled and annotated the complete mitochondrial genome of 30 S. endobioticum isolates and generated mitochondrial genomes for five additional chytrid species. The mitochondrial genome of S. endobioticum is linear with terminal inverted repeats which was validated by tailing and PCR amplifying the telomeric ends. Surprisingly, no conservation in organisation and orientation of mitochondrial genes was observed among the Chytridiomycota except for S. endobioticum and its sister species Synchytrium microbalum. However, the mitochondrial genome of S. microbalum is circular and comprises only a third of the 72.9 Kbp found for S. endobioticum suggesting recent linearization and expansion. Four mitochondrial lineages were identified in the S. endobioticum mitochondrial genomes. Several pathotypes occur in different lineages, suggesting that these have emerged independently. In addition, variations for polymorphic sites in the mitochondrial genome of individual isolates were observed demonstrating that S. endobioticum isolates represent a community of different genotypes. Such communities were shown to be complex and stable over time, but we also demonstrate that the use of semi-resistant potato cultivars triggers a rapid shift in the mitochondrial haplotype associated with increased virulence.

CONCLUSIONS: Mitochondrial genomic variation shows that S. endobioticum has been introduced into Europe multiple times, that several pathotypes emerged multiple times, and that isolates represent communities of different genotypes. Our study represents the most comprehensive dataset of chytrid mitogenomes, which provides new insights into the extraordinary dynamics and evolution of mitochondrial genomes involving linearization, expansion and reshuffling.}, } @article {pmid30200887, year = {2018}, author = {Sun, H and Hao, P and Ma, Q and Zhang, M and Qin, Y and Wei, H and Su, J and Wang, H and Gu, L and Wang, N and Liu, G and Yu, S}, title = {Genome-wide identification and expression analyses of the pectate lyase (PEL) gene family in cotton (Gossypium hirsutum L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {661}, pmid = {30200887}, issn = {1471-2164}, support = {2016YFD0101400//National Key Research and Development Program of China/ ; }, mesh = {Conserved Sequence ; Flowers/growth & development ; Genome, Plant/genetics ; *Genomics ; Gossypium/*enzymology/*genetics/growth & development/metabolism ; Indoleacetic Acids/metabolism ; Phylogeny ; Polysaccharide-Lyases/*genetics ; Promoter Regions, Genetic/genetics ; }, abstract = {BACKGROUND: Pectin is a major component and structural polysaccharide of the primary cell walls and middle lamella of higher plants. Pectate lyase (PEL, EC 4.2.2.2), a cell wall modification enzyme, degrades de-esterified pectin for cell wall loosening, remodeling and rearrangement. Nevertheless, there have been few studies on PEL genes and no comprehensive analysis of the PEL gene family in cotton.

RESULTS: We identified 53, 42 and 83 putative PEL genes in Gossypium raimondii (D5), Gossypium arboreum (A2), and Gossypium hirsutum (AD1), respectively. These PEL genes were classified into five subfamilies (I-V). Members from the same subfamilies showed relatively conserved gene structures, motifs and protein domains. An analysis of gene chromosomal locations and gene duplication revealed that segmental duplication likely contributed to the expansion of the GhPELs. The 2000 bp upstream sequences of all the GhPELs contained auxin response elements. A transcriptomic data analysis showed that 62 GhPELs were expressed in various tissues. Notably, most (29/32) GhPELs of subfamily IV were preferentially expressed in the stamen, and five GhPELs of subfamily V were prominently expressed at the fiber elongation stage. In addition, qRT-PCR analysis revealed the expression characteristics of 24 GhPELs in four pollen developmental stages and significantly different expression of some GhPELs between long- and short-fiber cultivars. Moreover, some members were responsive to IAA treatment. The results indicate that GhPELs play significant and functionally diverse roles in the development of different tissues.

CONCLUSIONS: In this study, we comprehensively analyzed PELs in G. hirsutum, providing a foundation to better understand the functions of GhPELs in different tissues and pathways, especially in pollen, fiber and the auxin signaling pathway.}, } @article {pmid30200886, year = {2018}, author = {Lübke, AL and Minatelli, S and Riedel, T and Lugert, R and Schober, I and Spröer, C and Overmann, J and Groß, U and Zautner, AE and Bohne, W}, title = {The transducer-like protein Tlp12 of Campylobacter jejuni is involved in glutamate and pyruvate chemotaxis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {111}, pmid = {30200886}, issn = {1471-2180}, abstract = {BACKGROUND: Campylobacter jejuni is one of the most common bacterial causes of food-borne enteritis worldwide. Chemotaxis in C. jejuni is known to be critical for the successful colonization of the host and key for the adaptation of the microbial species to different host environments. In C. jejuni, chemotaxis is regulated by a complex interplay of 13 or even more different chemoreceptors, also known as transducer-like proteins (Tlps). Recently, a novel chemoreceptor gene, tlp12, was described and found to be present in 29.5% of the investigated C. jejuni strains.

RESULTS: In this study, we present a functional analysis of Tlp12 with the aid of a tlp12 knockout mutant of the C. jejuni strain A17. Substrate specificity was investigated by capillary chemotaxis assays and revealed that Tlp12 plays an important role in chemotaxis towards glutamate and pyruvate. Moreover, the Δtlp12 mutant shows increased swarming motility in soft agar assays, an enhanced invasion rate into Caco-2 cells and an increased autoagglutination rate. The growth rate was slightly reduced in the Δtlp12 mutant. The identified phenotypes were in partial restored by complementation with the wild type gene. Tlp12-harboring C. jejuni strains display a strong association with chicken, whose excreta are known to contain high glutamate levels.

CONCLUSIONS: TLP12 is a chemoreceptor for glutamate and pyruvate recognition. Deletion of tlp12 has an influence on distinct physiological features, such as growth rate, swarming motility, autoagglutination and invasiveness.}, } @article {pmid30200885, year = {2018}, author = {Zeng, J and Quan, X and He, X and Cai, S and Ye, Z and Chen, G and Zhang, G}, title = {Root and leaf metabolite profiles analysis reveals the adaptive strategies to low potassium stress in barley.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {187}, pmid = {30200885}, issn = {1471-2229}, support = {31330055//National Natural Science Foundation of China (CN)/ ; 31601296//National Natural Science Foundation of China/ ; CARS-05//China Agriculture Research System/ ; JCIC-MCP//Jiangsu Collaborative Innovation Center for Modern Crop Production/ ; }, mesh = {*Adaptation, Physiological ; Hordeum/*metabolism ; Metabolome ; Plant Leaves/metabolism ; Plant Roots/metabolism ; Potassium/*metabolism ; Stress, Physiological ; }, abstract = {BACKGROUND: Potassium (K) deficiency in arable land is one of the most important factors affecting crop productivity. Development of low K (LK) tolerant crop cultivars is regarded as a best economic and effective approach for solving the issue of LK. In previous studies, we found a wider variation of LK tolerance in the Tibetan wild barley accessions than cultivated barley. However, the mechanism of LK tolerance in wild barley is still elusive.

RESULTS: In this study, two wild barley genotypes (XZ153, LK tolerant and XZ141, LK sensitive) and one cultivar (LuDaoMai, LK tolerant) was used to investigate metabolome changes in response to LK stress. Totally 57 kinds of metabolites were identified in roots and leaves of three genotypes at 16 d after LK treatment. In general, accumulation of amino acids and sugars was enhanced in both roots and leaves, while organic acids were reduced under LK stress compared to the control. Meanwhile, the concentrations of the negatively charged amino acids (Asp and Glu) and most organic acids was reduced in both roots and leaves, but more positively charged amino acids (Lys and Gln) were increased in three genotypes under LK. XZ153 had less reduction than other two genotypes in biomass and chlorophyll content under LK stress and showed greater antioxidant capacity as reflected by more synthesis of active oxygen scavengers. Higher LK tolerance of XZ153 may also be attributed to its less carbohydrate consumption and more storage of glucose and other sugars, thus providing more energy for plant growth under LK stress. Moreover, phenylpropanoid metabolic pathway mediated by PAL differed among three genotypes, which is closely associated with the genotypic difference in LK tolerance.

CONCLUSIONS: LK tolerance in the wild barley is attributed to more active phenylpropanoid metabolic pathway mediated by PAL, energy use economy by reducing carbohydrate consumption and storage of glucose and other sugars, and higher antioxidant defense ability under LK stress.}, } @article {pmid30200883, year = {2018}, author = {Fanelli, F and Liuzzi, VC and Logrieco, AF and Altomare, C}, title = {Genomic characterization of Trichoderma atrobrunneum (T. harzianum species complex) ITEM 908: insight into the genetic endowment of a multi-target biocontrol strain.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {662}, pmid = {30200883}, issn = {1471-2164}, support = {678781//Horizon 2020 Framework Programme/ ; }, mesh = {*Genomics ; Multigene Family/genetics ; Multilocus Sequence Typing ; Trichoderma/*genetics/metabolism ; }, abstract = {BACKGROUND: So far, biocontrol agent selection has been performed mainly by time consuming in vitro confrontation tests followed by extensive trials in greenhouse and field. An alternative approach is offered by application of high-throughput techniques, which allow extensive screening and comparison among strains for desired genetic traits. In the genus Trichoderma, the past assignments of particular features or strains to one species need to be reconsidered according to the recent taxonomic revisions. Here we present the genome of a biocontrol strain formerly known as Trichoderma harzianum ITEM 908, which exhibits both growth promoting capabilities and antagonism against different fungal pathogens, including Fusarium graminearum, Rhizoctonia solani, and the root-knot nematode Meloidogyne incognita. By genomic analysis of ITEM 908 we investigated the occurrence and the relevance of genes associated to biocontrol and stress tolerance, providing a basis for future investigation aiming to unravel the complex relationships between genomic endowment and exhibited activities of this strain.

RESULTS: The MLST analysis of ITS-TEF1 concatenated datasets reclassified ITEM 908 as T. atrobrunneum, a species recently described within the T. harzianum species complex and phylogenetically close to T. afroharzianum and T. guizhouense. Genomic analysis revealed the presence of a broad range of genes encoding for carbohydrate active enzymes (CAZYmes), proteins involved in secondary metabolites production, peptaboils, epidithiodioxopiperazines and siderophores potentially involved in parasitism, saprophytic degradation as well as in biocontrol and antagonistic activities. This abundance is comparable to other Trichoderma spp. in the T. harzianum species complex, but broader than in other biocontrol species and in the species T. reesei, known for its industrial application in cellulase production. Comparative analysis also demonstrated similar genomic organization of major secondary metabolites clusters, as in other Trichoderma species.

CONCLUSIONS: Reported data provide a contribution to a deeper understanding of the mode of action and identification of activity-specific genetic markers useful for selection and improvement of biocontrol strains. This work will also enlarge the availability of genomic data to perform comparative studies with the aim to correlate phenotypic differences with genetic diversity of Trichoderma species.}, } @article {pmid30200881, year = {2018}, author = {Zhu, A and Fan, W and Adams, RP and Mower, JP}, title = {Phylogenomic evidence for ancient recombination between plastid genomes of the Cupressus-Juniperus-Xanthocyparis complex (Cupressaceae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {137}, pmid = {30200881}, issn = {1471-2148}, support = {BU 0324512//Baylor University/International ; }, mesh = {Cupressaceae/*genetics ; Cupressus/genetics ; *Genome, Plastid ; *Genomics ; Juniperus/genetics ; *Phylogeny ; *Recombination, Genetic ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Phylogenetic relationships among Eastern Hemisphere cypresses, Western Hemisphere cypresses, junipers, and their closest relatives are controversial, and generic delimitations have been in flux for the past decade. To address relationships and attempt to produce a more robust classification, we sequenced 11 new plastid genomes (plastomes) from the five variously described genera in this complex (Callitropsis, Cupressus, Hesperocyparis, Juniperus, and Xanthocyparis) and compared them with additional plastomes from diverse members of Cupressaceae.

RESULTS: Phylogenetic analysis of protein-coding genes recovered a topology in which Juniperus is sister to Cupressus, whereas a tree based on whole plastomes indicated that the Callitropsis-Hesperocyparis-Xanthocyparis (CaHX) clade is sister to Cupressus. A sliding window analysis of site-specific phylogenetic support identified a ~ 15 kb region, spanning the genes ycf1 and ycf2, which harbored an anomalous signal relative to the rest of the genome. After excluding these genes, trees based on the remainder of the genes and genome consistently recovered a topology grouping the CaHX clade and Cupressus with strong bootstrap support. In contrast, trees based on the ycf1 and ycf2 region strongly supported a sister relationship between Cupressus and Juniperus.

CONCLUSIONS: These results demonstrate that standard phylogenomic analyses can result in strongly supported but conflicting trees. We suggest that the conflicting plastomic signals result from an ancient introgression event involving ycf1 and ycf2 that occurred in an ancestor of this species complex. The introgression event was facilitated by plastomic recombination in an ancestral heteroplasmic individual carrying distinct plastid haplotypes, offering further evidence that recombination occurs between plastomes. Finally, we provide strong support for previous proposals to recognize five genera in this species complex: Callitropsis, Cupressus, Hesperocyparis, Juniperus, and Xanthocyparis.}, } @article {pmid30200879, year = {2018}, author = {Irigoien, I and Arenas, C}, title = {Identification of differentially expressed genes by means of outlier detection.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {317}, pmid = {30200879}, issn = {1471-2105}, support = {TIN2015-64395-R//Spanish Ministerio de Economia y Competitividad/ ; SAF2015-68341-R//Spanish Ministerio de Economia y Competitividad/ ; }, mesh = {Biomarkers/*metabolism ; Gene Expression Profiling/*methods ; Humans ; Neoplasms/*genetics ; Oligonucleotide Array Sequence Analysis/methods ; }, abstract = {BACKGROUND: An important issue in microarray data is to select, from thousands of genes, a small number of informative differentially expressed (DE) genes which may be key elements for a disease. If each gene is analyzed individually, there is a big number of hypotheses to test and a multiple comparison correction method must be used. Consequently, the resulting cut-off value may be too small. Moreover, an important issue is the selection's replicability of the DE genes. We present a new method, called ORdensity, to obtain a reproducible selection of DE genes. It takes into account the relation between all genes and it is not a gene-by-gene approach, unlike the usually applied techniques to DE gene selection.

RESULTS: The proposed method returns three measures, related to the concepts of outlier and density of false positives in a neighbourhood, which allow us to identify the DE genes with high classification accuracy. To assess the performance of ORdensity, we used simulated microarray data and four real microarray cancer data sets. The results indicated that the method correctly detects the DE genes; it is competitive with other well accepted methods; the list of DE genes that it obtains is useful for the correct classification or diagnosis of new future samples and, in general, it is more stable than other procedures.

CONCLUSIONS: ORdensity is a new method for identifying DE genes that avoids some of the shortcomings of the individual gene identification and it is stable when the original sample is changed by subsamples.}, } @article {pmid30200878, year = {2018}, author = {Hua, C and Geng, Y and Chen, Q and Niu, L and Cai, L and Tao, S and Ni, Y and Zhao, R}, title = {Chronic dexamethasone exposure retards growth without altering the digestive tract microbiota composition in goats.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {112}, pmid = {30200878}, issn = {1471-2180}, abstract = {BACKGROUND: Dexamethasone (Dex), an artificially synthetic cortisol substitute, is commonly used as an anti-inflammatory drug, and is also employed to mimic the stress state experimentally. It is well known that chronic stress disturbs the gut microbiota community and digestive functions. However, no relevant studies have been conducted in ruminants.

RESULTS: In this study, a low dosage of Dex (0.2 mg/kg body weight, Dex group, n = 5) was consecutively injected intramuscularly for 21 days to simulate chronic stress in growing goats. Goats were injected with saline (0.2 mg/kg body weight) as the control group (Con, n = 5). Dex-treated goats showed a higher number of white blood cells and blood glucose levels (p < 0.01), but lower dry matter intake (DMI) and body weight (p < 0.01) than those of saline-injected goats. Plasma cortisol concentration decreased significantly in response to the Dex injection compared to the control (p < 0.05). The Dex treatment did not change most ruminal volatile fatty acid (VFAs) concentrations before the morning feeding after 1-21 days of treatment (p > 0.05); however, ruminal VFA concentrations decreased dramatically 2, 4, 6, and 8 h after the morning feeding on day 21 of the Dex injections. In this study, chronic Dex exposure did not alter the community structure of microbes or methanogenes in the rumen, caecum, or colonic digesta. Only Prevotella increased on days 7 and 14 of Dex treatment, but decreased on day 21, and Methanosphaera was the only genus of methanogene that decreased.

CONCLUSIONS: Our results suggest that chronic Dex exposure retards growth by decreasing DMI, which may be mediated by higher levels of blood glucose and lower ruminal VFA production. Microbiota in the digestive tract was highly resistant to chronic Dex exposure.}, } @article {pmid30200877, year = {2018}, author = {Flores, MA and Ovcharenko, I}, title = {Enhancer reprogramming in mammalian genomes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {316}, pmid = {30200877}, issn = {1471-2105}, mesh = {Animals ; *Enhancer Elements, Genetic ; *Gene Expression Regulation ; *Genome ; Humans ; Mice ; Phenotype ; }, abstract = {BACKGROUND: Transcription factor binding site (TFBS) loss, gain, and reshuffling within the sequence of a regulatory element could alter the function of that regulatory element. Some of the changes will be detrimental to the fitness of the species and will result in gradual removal from a population, while other changes would be either beneficial or just a part of genetic drift and end up being fixed in a population. This "reprogramming" of regulatory elements results in modification of the gene regulatory landscape during evolution.

RESULTS: We identified reprogrammed enhancers (RPEs) by comparing the distribution of tissue-specific enhancers in the human and mouse genomes. We observed that around 30% of mammalian enhancers have been reprogrammed after the human-mouse speciation. In 79% of cases, the reprogramming of an enhancer resulted in a quantifiably different expression of a flanking gene. In the case of the Thy-1 cell surface antigen gene, for example, enhancer reprogramming is associated with cortex to thymus change in gene expression. To understand the mechanisms of enhancer reprogramming, we profiled the evolutionary changes in the TFBS enhancer content and found that enhancer reprogramming took place through the acquisition of new TFBSs in 72% of reprogramming events.

CONCLUSIONS: Our results suggest that enhancer reprogramming takes place within well-established regulatory loci with RPEs contributing additively to fine-tuning of the gene regulatory program in mammals. We also found evidence for acquisition of novel gene function through enhancer reprogramming, which allows expansion of gene regulatory landscapes into new regulatory domains.}, } @article {pmid30200876, year = {2018}, author = {Yang, S and Du, J and Duan, YL and Xiao, Q and Li, NQ and Lin, Q and Zhao, LL and Du, ZJ and Zhou, J and Du, J}, title = {Differences in the digestive enzyme activity, intestinal mucosa and microbial community in loach cultivated in two separate environments.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {113}, pmid = {30200876}, issn = {1471-2180}, abstract = {BACKGROUND: Fish culture in rice paddies can contribute to increasing yields of rice and surplus fish products. Environmental impacts and food-safety issues have become important topics in aquaculture, and organic foods currently were paid attention by researchers and industry practitioners. But the mechanism of differences in quality of Loach (Paramisgurnus dabryanus) reared in rice fields and ponds remains largely uncharacterized. In this study,digestive enzyme activity, intestinal mucosa cells and the gut microbial community of loach were determined under the two separate cultivation modes.

RESULTS: The levels of intestinal digestive enzyme activity of fish reared in the paddy-cultivated mode (PACM) were higher (P < 0.05) than those in the pond-cultivated mode (POCM). It was extremely significant (P < 0.01) for the activity of lipase in the liver, foregut and midgut, and for the activities of amylase and trypsin in the hindgut. Acid mucous cells in the loach foregut in PACM were fewer than in POCM (P < 0.01). In summer, the abundance of the Firmicutes, Lactobacillus spp., Aeromonas hydrophila, Enterobacteriaceae and Streptococcus spp. in loach intestinal mucosa in PACM was higher than in POCM. In fall, the abundance of total bacteria, the Bacteroidetes, Bifidobacterium and Enterobacteriaceae in the intestinal mucosa in PACM was likewise higher than in POCM. These differences were significant (P < 0.05 or P < 0.01) between loach in the two separate culture modes for all microorganisms except for A. hydrophila and Streptococcus spp. In addition, quantitative PCR assays showed that some microorganisms presented consistently similar abundances in the gut as in the culture water.

CONCLUSIONS: These results showed some enzymatic activities involved in digestion in liver and intestine of loach in PACM were higher than those in POCM, as using digestive enzyme analysis and histological observation of intestinal sections. These findings suggest most of the microorganisms examined in the gut mucosa of loach in the two culture modes significantly differed in abundance between summer and fall. However, some pathogenic bacteria in the gut, particularly A. hydrophila, presented lower abundance in PACM in fall, yet did not differ in abundance between loach in the two cultivation modes.}, } @article {pmid30200875, year = {2018}, author = {Beaujois, R and Ottoni, E and Zhang, X and Gagnon, C and Hassine, S and Mollet, S and Viranaicken, W and DesGroseillers, L}, title = {Correction to: The M-phase specific hyperphosphorylation of Staufen2 involved the cyclin-dependent kinase CDK1.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {20}, pmid = {30200875}, issn = {1471-2121}, abstract = {Following publication of the original article [1], the authors reported a change to one of the author names.}, } @article {pmid30200874, year = {2018}, author = {Alobaidi, M and Malik, KM and Sabra, S}, title = {Linked open data-based framework for automatic biomedical ontology generation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {319}, pmid = {30200874}, issn = {1471-2105}, mesh = {*Biological Ontologies ; *Biomedical Research ; Humans ; Knowledge Bases ; *Natural Language Processing ; *Semantics ; }, abstract = {BACKGROUND: Fulfilling the vision of Semantic Web requires an accurate data model for organizing knowledge and sharing common understanding of the domain. Fitting this description, ontologies are the cornerstones of Semantic Web and can be used to solve many problems of clinical information and biomedical engineering, such as word sense disambiguation, semantic similarity, question answering, ontology alignment, etc. Manual construction of ontology is labor intensive and requires domain experts and ontology engineers. To downsize the labor-intensive nature of ontology generation and minimize the need for domain experts, we present a novel automated ontology generation framework, Linked Open Data approach for Automatic Biomedical Ontology Generation (LOD-ABOG), which is empowered by Linked Open Data (LOD). LOD-ABOG performs concept extraction using knowledge base mainly UMLS and LOD, along with Natural Language Processing (NLP) operations; and applies relation extraction using LOD, Breadth first Search (BSF) graph method, and Freepal repository patterns.

RESULTS: Our evaluation shows improved results in most of the tasks of ontology generation compared to those obtained by existing frameworks. We evaluated the performance of individual tasks (modules) of proposed framework using CDR and SemMedDB datasets. For concept extraction, evaluation shows an average F-measure of 58.12% for CDR corpus and 81.68% for SemMedDB; F-measure of 65.26% and 77.44% for biomedical taxonomic relation extraction using datasets of CDR and SemMedDB, respectively; and F-measure of 52.78% and 58.12% for biomedical non-taxonomic relation extraction using CDR corpus and SemMedDB, respectively. Additionally, the comparison with manually constructed baseline Alzheimer ontology shows F-measure of 72.48% in terms of concepts detection, 76.27% in relation extraction, and 83.28% in property extraction. Also, we compared our proposed framework with ontology-learning framework called "OntoGain" which shows that LOD-ABOG performs 14.76% better in terms of relation extraction.

CONCLUSION: This paper has presented LOD-ABOG framework which shows that current LOD sources and technologies are a promising solution to automate the process of biomedical ontology generation and extract relations to a greater extent. In addition, unlike existing frameworks which require domain experts in ontology development process, the proposed approach requires involvement of them only for improvement purpose at the end of ontology life cycle.}, } @article {pmid30200873, year = {2018}, author = {Cao, Y and Gao, X and Yang, Y and Ye, Z and Wang, E and Dong, Z}, title = {Changing expression profiles of long non-coding RNAs, mRNAs and circular RNAs in ethylene glycol-induced kidney calculi rats.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {660}, pmid = {30200873}, issn = {1471-2164}, mesh = {Animals ; Ethylene Glycol/*pharmacology ; Gene Ontology ; Kidney Calculi/*chemically induced/*genetics/pathology ; Male ; RNA/*genetics ; RNA, Long Noncoding/*genetics ; RNA, Messenger/genetics ; Rats ; Rats, Sprague-Dawley ; Sequence Analysis, RNA ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: To explore long non-coding RNA (lncRNA), mRNA and circular RNA (circRNA) expression profiles and their biological functions in the pathogenesis of kidney stones in ethylene glycol-induced urolithiasis rats.

RESULTS: The expression of 1440 lncRNAs, 2455 mRNAs and 145 circRNAs was altered in the kidneys of urolithiasis rats. GO and KEGG biological pathway analysis were performed to predict the functions of differentially expressed lncRNAs, circRNAs and co-expressed potential targeting genes. Co-expression networks of lncRNA-mRNA and circRNA-miRNA were constructed based on correlation analysis between differentially expressed RNAs. mRNAs coexpressed with lncRNAs were involved in many kidney diseases, e.g., Ephb6 was associated with the reabsorption ability of the kidney. Arl5b was associated with the dynamic changes in the podocyte foot process in podocyte injury. miRNAs co-expressed with circRNAs, such as rno-miR-138-5p and rno-miR-672-5p, have been proven to be functional in hypercalciuria urolithiasis.

CONCLUSION: The expression profile provided a systematic perspective on the potential functions of lncRNAs and circRNAs in the pathogenesis of kidney stones. Differentially expressed lncRNAs and circRNAs might serve as treatment targets for kidney stones.}, } @article {pmid30200872, year = {2018}, author = {Thyssen, GN and Naoumkina, M and McCarty, JC and Jenkins, JN and Florane, C and Li, P and Fang, DD}, title = {The P450 gene CYP749A16 is required for tolerance to the sulfonylurea herbicide trifloxysulfuron sodium in cotton (Gossypium hirsutum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {186}, pmid = {30200872}, issn = {1471-2229}, support = {6054-21000-017-00D//USDA-ARS/ ; }, mesh = {Chromosome Mapping ; Chromosomes, Plant ; Cytochrome P-450 Enzyme System/*genetics ; Gene Silencing ; Gossypium/drug effects/enzymology/*genetics ; Herbicide Resistance/*genetics ; Herbicides/*toxicity ; Mutation ; Pyridines/*toxicity ; Sulfonamides/*toxicity ; }, abstract = {BACKGROUND: Weed management is critical to global crop production and is complicated by rapidly evolving herbicide resistance in weeds. New sources of herbicide resistance are needed for crop plants so that applied herbicides can be rotated or combined to thwart the evolution of resistant weeds. The diverse family of cytochrome P450 proteins has been suggested to be a source of detoxifying herbicide metabolism in both weed and crop plants, and greater understanding of these genes will offer avenues for crop improvement and novel weed management practices.

RESULTS: Here, we report the identification of CYP749A16 (Gh_D10G1401) which is responsible for the natural tolerance exhibited by most cotton, Gossypium hirsutum L., cultivars to the herbicide trifloxysulfuron sodium (TFS, CGA 362622, commercial formulation Envoke). A 1-bp frameshift insertion in the third exon of CYP749A16 results in the loss of tolerance to TFS. The DNA marker designed from this insertion perfectly co-segregated with the phenotype in 2145 F2 progeny of a cross between the sensitive cultivar Paymaster HS26 and tolerant cultivar Stoneville 474, and in 550 recombinant inbred lines of a multi-parent advanced generation inter-cross population. Marker analysis of 382 additional cotton cultivars identified twelve cultivars containing the 1-bp frameshift insertion. The marker genotypes matched perfectly with phenotypes in 188 plants from the selected twelve cultivars. Virus-induced gene silencing of CYP749A16 generated sensitivity in the tolerant cotton cultivar Stoneville 474.

CONCLUSIONS: CYP749A16 located on chromosome D10 is required for TFS herbicide tolerance in cotton. This finding should add to the repertoire of tools available to farmers and breeders for the advancement of agricultural productivity.}, } @article {pmid30200857, year = {2018}, author = {Gourse, RL and Chen, AY and Gopalkrishnan, S and Sanchez-Vazquez, P and Myers, A and Ross, W}, title = {Transcriptional Responses to ppGpp and DksA.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {163-184}, doi = {10.1146/annurev-micro-090817-062444}, pmid = {30200857}, issn = {1545-3251}, abstract = {The stringent response to nutrient deprivation is a stress response found throughout the bacterial domain of life. Although first described in proteobacteria for matching ribosome synthesis to the cell's translation status and for preventing formation of defective ribosomal particles, the response is actually much broader, regulating many hundreds of genes-some positively, some negatively. Utilization of the signaling molecules ppGpp and pppGpp for this purpose is ubiquitous in bacterial evolution, although the mechanisms employed vary. In proteobacteria, the signaling molecules typically bind to two sites on RNA polymerase, one at the interface of the β' and ω subunits and one at the interface of the β' secondary channel and the transcription factor DksA. The β' secondary channel is targeted by other transcription regulators as well. Although studies on the transcriptional outputs of the stringent response date back at least 50 years, the mechanisms responsible are only now coming into focus.}, } @article {pmid30200856, year = {2018}, author = {Laurens, MB}, title = {The Promise of a Malaria Vaccine-Are We Closer?.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {273-292}, doi = {10.1146/annurev-micro-090817-062427}, pmid = {30200856}, issn = {1545-3251}, abstract = {Malaria vaccine development has rapidly advanced in the past decade. The very first phase 3 clinical trial of the RTS,S vaccine was completed with over 15,000 African infants and children, and pilot implementation studies are underway. Next-generation candidate vaccines using novel antigens, platforms, or approaches targeting different and/or multiple stages of the Plasmodium life cycle are being tested. Many candidates, in various stages of development, promise enhanced efficacy of long duration and broad protection against genetically diverse malaria strains, with a few studies under way in target populations in endemic areas. Malaria vaccines together with other interventions promise interruption and eventual elimination of malaria in endemic areas.}, } @article {pmid30200855, year = {2018}, author = {Langdon, EM and Gladfelter, AS}, title = {A New Lens for RNA Localization: Liquid-Liquid Phase Separation.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {255-271}, doi = {10.1146/annurev-micro-090817-062814}, pmid = {30200855}, issn = {1545-3251}, abstract = {RNA localization mechanisms have been intensively studied and include localized protection of mRNA from degradation, diffusion-coupled local entrapment of mRNA, and directed transport of mRNAs along the cytoskeleton. While it is well understood how cells utilize these three mechanisms to organize mRNAs within the cytoplasm, a newly appreciated mechanism of RNA localization has emerged in recent years in which mRNAs phase-separate and form liquid-like droplets. mRNAs both contribute to condensation of proteins into liquid-like structures and are themselves regulated by being incorporated into membraneless organelles. This ability to condense into droplets is in many instances contributing to previously appreciated mRNA localization phenomena. Here we review how phase separation enables mRNAs to selectively and efficiently colocalize and be coregulated, allowing control of gene expression in time and space.}, } @article {pmid30200854, year = {2018}, author = {Tan, X and Sun, L and Chen, J and Chen, ZJ}, title = {Detection of Microbial Infections Through Innate Immune Sensing of Nucleic Acids.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {447-478}, doi = {10.1146/annurev-micro-102215-095605}, pmid = {30200854}, issn = {1545-3251}, abstract = {Microbial infections are recognized by the innate immune system through germline-encoded pattern recognition receptors (PRRs). As most microbial pathogens contain DNA and/or RNA during their life cycle, nucleic acid sensing has evolved as an essential strategy for host innate immune defense. Pathogen-derived nucleic acids with distinct features are recognized by specific host PRRs localized in endolysosomes and the cytosol. Activation of these PRRs triggers signaling cascades that culminate in the production of type I interferons and proinflammatory cytokines, leading to induction of an antimicrobial state, activation of adaptive immunity, and eventual clearance of the infection. Here, we review recent progress in innate immune recognition of nucleic acids upon microbial infection, including pathways involving endosomal Toll-like receptors, cytosolic RNA sensors, and cytosolic DNA sensors. We also discuss the mechanisms by which infectious microbes counteract host nucleic acid sensing to evade immune surveillance.}, } @article {pmid30200853, year = {2018}, author = {Braun, V}, title = {The Outer Membrane Took Center Stage.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {1-24}, doi = {10.1146/annurev-micro-090817-062156}, pmid = {30200853}, issn = {1545-3251}, abstract = {My interest in membranes was piqued during a lecture series given by one of the founders of molecular biology, Max Delbrück, at Caltech, where I spent a postdoctoral year to learn more about protein chemistry. That general interest was further refined to my ultimate research focal point-the outer membrane of Escherichia coli-through the influence of the work of Wolfhard Weidel, who discovered the murein (peptidoglycan) layer and biochemically characterized the first phage receptors of this bacterium. The discovery of lipoprotein bound to murein was completely unexpected and demonstrated that the protein composition of the outer membrane and the structure and function of proteins could be unraveled at a time when nothing was known about outer membrane proteins. The research of my laboratory over the years covered energy-dependent import of proteinaceous toxins and iron chelates across the outer membrane, which does not contain an energy source, and gene regulation by iron, including transmembrane transcriptional regulation.}, } @article {pmid30200852, year = {2018}, author = {Dolan, SK and Welch, M}, title = {The Glyoxylate Shunt, 60 Years On.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {309-330}, doi = {10.1146/annurev-micro-090817-062257}, pmid = {30200852}, issn = {1545-3251}, abstract = {2017 marks the 60th anniversary of Krebs' seminal paper on the glyoxylate shunt (and coincidentally, also the 80th anniversary of his discovery of the citric acid cycle). Sixty years on, we have witnessed substantial developments in our understanding of how flux is partitioned between the glyoxylate shunt and the oxidative decarboxylation steps of the citric acid cycle. The last decade has shown us that the beautifully elegant textbook mechanism that regulates carbon flux through the shunt in E. coli is an oversimplification of the situation in many other bacteria. The aim of this review is to assess how this new knowledge is impacting our understanding of flux control at the TCA cycle/glyoxylate shunt branch point in a wider range of genera, and to summarize recent findings implicating a role for the glyoxylate shunt in cellular functions other than metabolism.}, } @article {pmid30200851, year = {2018}, author = {Feldmann, H and Feldmann, F and Marzi, A}, title = {Ebola: Lessons on Vaccine Development.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {423-446}, doi = {10.1146/annurev-micro-090817-062414}, pmid = {30200851}, issn = {1545-3251}, abstract = {The West African Ebola virus (EBOV) epidemic has fast-tracked countermeasures for this rare, emerging zoonotic pathogen. Until 2013-2014, most EBOV vaccine candidates were stalled between the preclinical and clinical milestones on the path to licensure, because of funding problems, lack of interest from pharmaceutical companies, and competing priorities in public health. The unprecedented and devastating epidemic propelled vaccine candidates toward clinical trials that were initiated near the end of the active response to the outbreak. Those trials did not have a major impact on the epidemic but provided invaluable data on vaccine safety, immunogenicity, and, to a limited degree, even efficacy in humans. There are plenty of lessons to learn from these trials, some of which are addressed in this review. Better preparation is essential to executing an effective response to EBOV in the future; yet, the first indications of waning interest are already noticeable.}, } @article {pmid30200850, year = {2018}, author = {Blázquez, J and Rodríguez-Beltrán, J and Matic, I}, title = {Antibiotic-Induced Genetic Variation: How It Arises and How It Can Be Prevented.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {209-230}, doi = {10.1146/annurev-micro-090817-062139}, pmid = {30200850}, issn = {1545-3251}, abstract = {By targeting essential cellular processes, antibiotics provoke metabolic perturbations and induce stress responses and genetic variation in bacteria. Here we review current knowledge of the mechanisms by which these molecules generate genetic instability. They include production of reactive oxygen species, as well as induction of the stress response regulons, which lead to enhancement of mutation and recombination rates and modulation of horizontal gene transfer. All these phenomena influence the evolution and spread of antibiotic resistance. The use of strategies to stop or decrease the generation of resistant variants is also discussed.}, } @article {pmid30200849, year = {2018}, author = {Croucher, NJ and Løchen, A and Bentley, SD}, title = {Pneumococcal Vaccines: Host Interactions, Population Dynamics, and Design Principles.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {521-549}, doi = {10.1146/annurev-micro-090817-062338}, pmid = {30200849}, issn = {1545-3251}, abstract = {Streptococcus pneumoniae (the pneumococcus) is a nasopharyngeal commensal and respiratory pathogen. Most isolates express a capsule, the species-wide diversity of which has been immunologically classified into ∼100 serotypes. Capsule polysaccharides have been combined into multivalent vaccines widely used in adults, but the T cell independence of the antibody response means they are not protective in infants. Polysaccharide conjugate vaccines (PCVs) trigger a T cell-dependent response through attaching a carrier protein to capsular polysaccharides. The immune response stimulated by PCVs in infants inhibits carriage of vaccine serotypes (VTs), resulting in population-wide herd immunity. These were replaced in carriage by non-VTs. Nevertheless, PCVs drove reductions in infant pneumococcal disease, due to the lower mean invasiveness of the postvaccination bacterial population; age-varying serotype invasiveness resulted in a smaller reduction in adult disease. Alternative vaccines being tested in trials are designed to provide species-wide protection through stimulating innate and cellular immune responses, alongside antibodies to conserved antigens.}, } @article {pmid30200848, year = {2018}, author = {Carrier, MC and Lalaouna, D and Massé, E}, title = {Broadening the Definition of Bacterial Small RNAs: Characteristics and Mechanisms of Action.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {141-161}, doi = {10.1146/annurev-micro-090817-062607}, pmid = {30200848}, issn = {1545-3251}, abstract = {The first report of trans-acting RNA-based regulation in bacterial cells dates back to 1984. Subsequent studies in diverse bacteria unraveled shared properties of trans-acting small regulatory RNAs, forming a clear definition of these molecules. These shared characteristics have been used extensively to identify new small RNAs (sRNAs) and their interactomes. Recently however, emerging technologies able to resolve RNA-RNA interactions have identified new types of regulatory RNAs. In this review, we present a broader definition of trans-acting sRNA regulators and discuss their newly discovered intrinsic characteristics.}, } @article {pmid30200847, year = {2018}, author = {Gottesman, S}, title = {Introduction.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {i-ii}, doi = {10.1146/annurev-mi-72-070918-100001}, pmid = {30200847}, issn = {1545-3251}, } @article {pmid30198555, year = {2018}, author = {Tanaka, KM and Kamimura, Y and Takahashi, A}, title = {Mechanical incompatibility caused by modifications of multiple male genital structures using genomic introgression in Drosophila.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2406-2418}, doi = {10.1111/evo.13592}, pmid = {30198555}, issn = {1558-5646}, support = {15J05233//Japan Society for the Promotion of Science/ ; 15K07133//Japan Society for the Promotion of Science/ ; }, abstract = {Mechanical incompatibility of male and female genitalia is common in animals with internal fertilization. However, our knowledge regarding the precise mechanisms is limited. One key question regards the susceptibility of the match between male and female genitalia to morphological modification. To address this issue, we generated six different second-chromosome introgression lines possessing partially Drosophila mauritiana-like genital morphology in multiple structures in D. simulans background. Three of the six introgression males showed elevated mobility at some stages during copulation with D. simulans females; this was assumed to be an indication of genital mismatch. Notably, one of the introgression males with D. mauritiana-like enlarged anal plates showed occasional leakage of adhesive ejaculate on the body surface when mated with pure D. simulans females, suggesting apparent structural incompatibility in genital coupling. These observations suggested that both sexual and natural selection shape the anal plate morphology, highlighting the role of this structure as an important component of mechanical isolation. Partial replacement (introgression) by a sibling species genome can induce perturbations in genital coupling mechanics, suggesting that genital compatibility can be susceptible to subtle genomic changes at the early stages of divergence in these species.}, } @article {pmid30198178, year = {2018}, author = {Koonin, EV}, title = {Environmental microbiology and metagenomics: the Brave New World is here, what's next?.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4210-4212}, doi = {10.1111/1462-2920.14403}, pmid = {30198178}, issn = {1462-2920}, } @article {pmid30198168, year = {2018}, author = {Torti, A and Jørgensen, BB and Lever, MA}, title = {Preservation of microbial DNA in marine sediments: insights from extracellular DNA pools.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4526-4542}, doi = {10.1111/1462-2920.14401}, pmid = {30198168}, issn = {1462-2920}, support = {//Danish National Research Foundation/ ; 294200//European Research Council/International ; }, abstract = {Marine sediments harbour extracellular DNA (exDNA) not associated with currently living organisms. Including this exDNA in genetic surveys may distort abundance and diversity estimates of living prokaryotic communities. We separately extract exDNA and intracellular DNA (inDNA) from 11 horizons in a 10-m deep sediment core from Aarhus Bay (Denmark) that spans > 9000 years of Holocene sedimentation. We compare depth profiles of bacterial and archaeal 16S rRNA gene compositions to those of macrofaunal activity (bioturbation), sulfate and methane concentrations, sediment age and lithology. Among these variables, bioturbation shows the strongest relationship with the two DNA pools. In bioturbated surface sediments, the majority of Operational Taxonomic Units (OTUs) present in exDNA is absent from inDNA, thus belonging to microorganisms that were not alive at the time of sampling. Below the bioturbation zone, the two DNA pools display a much higher phylogenetic similarity. At all depths, the majority of exDNA and inDNA sequences show highest sequence similarities to sediment microorganisms, a finding that is additionally supported by separate analyses on low- and high-molecular weight exDNA. Our results indicate that in Aarhus Bay the vast majority of prokaryotic exDNA is turned over, thus not contributing to a genetic archive of past environmental change.}, } @article {pmid30198108, year = {2018}, author = {Landis, MJ and Freyman, WA and Baldwin, BG}, title = {Retracing the Hawaiian silversword radiation despite phylogenetic, biogeographic, and paleogeographic uncertainty.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2343-2359}, doi = {10.1111/evo.13594}, pmid = {30198108}, issn = {1558-5646}, support = {1601402//Division of Environmental Biology/ ; 9458237//Division of Environmental Biology/ ; 1612153//Directorate for Biological Sciences/ ; Donnelley Postdoctoral Fellowship//Institute for Biospheric Studies, Yale University/ ; 1106400//Division of Graduate Education/ ; }, abstract = {The Hawaiian silversword alliance (Asteraceae) is an iconic adaptive radiation. However, like many island plant lineages, no fossils have been assigned to the clade. As a result, the clade's age and diversification rate are not known precisely, making it difficult to test biogeographic hypotheses about the radiation. In lieu of fossils, paleogeographically structured biogeographic processes may inform species divergence times; for example, an island must first exist for a clade to radiate upon it. We date the silversword clade and test biogeographic hypotheses about its radiation across the Hawaiian Archipelago by modeling interactions between species relationships, molecular evolution, biogeographic scenarios, divergence times, and island origination times using the Bayesian phylogenetic framework, RevBayes. The ancestor of living silverswords most likely colonized the modern Hawaiian Islands once from the mainland approximately 5.1 Ma, with the most recent common ancestor of extant silversword lineages first appearing approximately 3.5 Ma. Applying an event-based test of the progression rule of island biogeography, we found strong evidence that the dispersal process favors old-to-young directionality, but strong evidence for diversification continuing unabated into later phases of island ontogeny, particularly for Kaua'i. This work serves as a general example for how diversification studies benefit from incorporating biogeographic and paleogeographic components.}, } @article {pmid30197732, year = {2018}, author = {Khan, LB and Read, HM}, title = {A Simple Exercise for Teaching Bacteriophage Concepts in the Undergraduate Laboratory Using Commercially Available Disinfectant.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30197732}, issn = {1935-7877}, } @article {pmid30197731, year = {2018}, author = {Elliott, S}, title = {It Takes a Village: Workflow to Publish a Peer-Reviewed Article.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, doi = {10.1128/jmbe.v19i2.1680}, pmid = {30197731}, issn = {1935-7877}, } @article {pmid30197730, year = {2018}, author = {Cooper, KM and Brownell, SE}, title = {Developing Course-Based Research Experiences in Discipline-Based Education Research: Lessons Learned and Recommendations.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30197730}, issn = {1935-7877}, abstract = {In this perspective, we highlight the opportunity for the biology education research community to develop course-based research experiences (CREs) or course-based undergraduate research experiences (CUREs) in discipline-based education research. Building on our prior experience developing and teaching four biology education research CREs, we present opportunities, potential pitfalls, and recommendations for discipline-based education researchers interested in integrating their research and teaching in the context of a CRE.}, } @article {pmid30197729, year = {2018}, author = {Bitacura, JG}, title = {The Use of Baker's Yeast in the Resazurin Reduction Test: A Simple, Low-Cost Method for Determining Cell Viability in Proliferation and Cytotoxicity Assays.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30197729}, issn = {1935-7877}, } @article {pmid30197728, year = {2018}, author = {Harrison, E}, title = {Role-Playing Activity to Demonstrate Diffusion Across a Cell Membrane.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30197728}, issn = {1935-7877}, } @article {pmid30197727, year = {2018}, author = {Schwingel, JM}, title = {Exploring Infectious Disease Outbreaks and Herd Immunity Through Simulations with a Visual Appeal.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30197727}, issn = {1935-7877}, } @article {pmid30197726, year = {2018}, author = {Christian, N and Kearns, KD}, title = {Using Scaffolding and Deliberate Practice to Improve Abstract Writing in an Introductory Biology Laboratory Course.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30197726}, issn = {1935-7877}, abstract = {s play the pivotal role of selling an article to a prospective reader, and for students, the ability to communicate science in concise written form may foster scientific thinking. However, students struggle with abstract composition, and we lack evidence-based educational innovations to help them develop this skill. We designed, implemented, and assessed an intervention for abstract composition with elements of scaffolding and transparency to ask whether deliberate practice improves concise scientific writing in early career undergraduate biology majors. We evaluated student performance by analyzing abstracts written before and after the intervention and by assessing pre- and posttest student concept maps. We found that scaffolded learning improved student abstract writing, with the greatest gains in students' ability to describe the motivation for their work. Using a set of tested tools to teach scientific writing has important implications for strengthening students' capacity to reinforce and synthesize content in the future, whether that is in laboratory course exercises, in independent research, or as a transferable skill to general critical thinking.}, } @article {pmid30195635, year = {2018}, author = {Hugo, RLE and Birrell, GW}, title = {Proteomics of Anopheles Vectors of Malaria.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {961-981}, doi = {10.1016/j.pt.2018.08.009}, pmid = {30195635}, issn = {1471-5007}, abstract = {Proteomic investigations in Anopheles gained momentum following the sequencing of the Anopheles gambiae genome, allowing peptide data from mass spectrometry to be searched against large datasets of predicted protein sequences. Exhaustive discovery proteomics investigations have improved the annotation of genomic datasets and catalogued proteins from mosquito tissues, including the salivary glands, midgut, and sensory appendages. These efforts have revealed protein constituents that define the unique biological functions of these organs. Quantitative proteomics investigations have begun to characterise the molecular basis of mosquito behaviour and immune responses. With a current trend towards increasing sensitivity of mass spectrometers and simpler workflows, proteomics is set to accelerate the development of antiparasite interventions through the identification of new targets for parasite or vector control and diagnostic biomarkers.}, } @article {pmid30195634, year = {2018}, author = {Sabourin, E and Alda, P and Vázquez, A and Hurtrez-Boussès, S and Vittecoq, M}, title = {Impact of Human Activities on Fasciolosis Transmission.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {891-903}, doi = {10.1016/j.pt.2018.08.004}, pmid = {30195634}, issn = {1471-5007}, mesh = {Agriculture ; Animals ; Diet ; Fascioliasis/epidemiology/prevention & control/*transmission ; Human Activities/*statistics & numerical data ; Humans ; Risk Factors ; }, abstract = {Fasciolosis is a worldwide disease caused by the liver fluke Fasciola spp. This food- and water-borne disease is a major public health and veterinary issue. It is currently (re)emerging in several regions mainly due to the rapid evolution of human activities. This article reviews the current knowledge of the impact of irrigation-system management, livestock management, and human diet and hygiene habits on the emergence of fasciolosis. We also identify the gaps in this knowledge and the possible solutions for limiting these impacts. Integrated control seems to be the most effective solution for controlling fasciolosis, because it enables monitoring, prevention, and rapid action in case of the (re)emergence of the disease.}, } @article {pmid30195581, year = {2018}, author = {Tiwari, B and Jones, AE and Abrams, JM}, title = {Transposons, p53 and Genome Security.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {11}, pages = {846-855}, pmid = {30195581}, issn = {0168-9525}, support = {R01 CA222579/CA/NCI NIH HHS/United States ; R01 GM072124/GM/NIGMS NIH HHS/United States ; R01 GM115682/GM/NIGMS NIH HHS/United States ; }, abstract = {p53, the most commonly mutated tumor suppressor, is a transcription factor known to regulate proliferation, senescence, and apoptosis. Compelling studies have found that p53 may prevent oncogenesis through effectors that are unrelated to these canonical processes and recent findings have uncovered ancient roles for p53 in the containment of mobile elements. Together, these developments raise the possibility that some p53-driven cancers could result from unrestrained transposons. Here, we explore evidence linking conserved features of p53 biology to the control of transposons. We also show how p53-deficient cells can be exploited to probe the behavior of transposons and illustrate how unrestrained transposons incited by p53 loss might contribute to human malignancies.}, } @article {pmid30195580, year = {2018}, author = {Gerst, JE}, title = {Pimp My Ribosome: Ribosomal Protein Paralogs Specify Translational Control.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {11}, pages = {832-845}, doi = {10.1016/j.tig.2018.08.004}, pmid = {30195580}, issn = {0168-9525}, abstract = {The ability of cells to grow and divide, differentiate and function, and even senesce is dependent on the fine-tuning of both gene and protein expression. Protein concentration in the cell is regulated not only at the transcriptional and post-translational levels, but also at the level of translation. Ribosomes, the molecular machines behind translation, were once considered to be an invariant driving force behind protein expression. However, studies over the past decade paint a rather different picture; namely, that ribosomes constitute an additional layer of regulatory control that might define which subsets of mRNAs are translated, to what extent, and to what purpose. Recent works summarized herein directly implicate ribosome heterogeneity and, in particular, ribosomal protein (RP) paralog specificity in regulating mRNA translation and control of the cellular translatome.}, } @article {pmid30195477, year = {2018}, author = {Ma, ZY and Wen, J and Ickert-Bond, SM and Nie, ZL and Chen, LQ and Liu, XQ}, title = {Phylogenomics, biogeography, and adaptive radiation of grapes.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {258-267}, doi = {10.1016/j.ympev.2018.08.021}, pmid = {30195477}, issn = {1095-9513}, abstract = {The application of whole-genome resequencing based on next-generation sequencing technologies provides an unprecedented opportunity for researchers to resolve long-standing evolutionary problems. Taxa belonging to the grape genus (Vitis L.) represent important genetic resources for the improvement of cultivated grapes. However, it has been challenging to resolve the deep phylogenetic relationships within Vitis, limiting the current understanding of the evolutionary history of Vitis and preventing the use of valuable wild grape resources. In this study, we obtained whole-genome sequence data from 41 accessions representing most taxa within subgenus Vitis and aligned these sequences to the Vitis vinifera L. reference genome. We reconstructed deep phylogenetic relationships within subgenus Vitis based on 2068 single-copy orthologous genes, which led to a robust topology with bootstrap support values of 100% for almost all branches. Three main clades are recovered within subgenus Vitis reflecting their continental distribution through North America, Europe, and East Asia, respectively. Our results suggest that the most possible migration route of the East Asian Vitis is from northeastern Asia southward to South Asia and Southeast Asia. The East Asian Vitis seems to have experienced adaptive radiation during the Miocene. This study provides novel insights into the diversification history of the grape genus Vitis.}, } @article {pmid30195476, year = {2018}, author = {Bogdanova, VS and Mglinets, AV and Shatskaya, NV and Kosterin, OE and Solovyev, VI and Vasiliev, GV}, title = {Cryptic divergences in the genus Pisum L. (peas), as revealed by phylogenetic analysis of plastid genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {280-290}, doi = {10.1016/j.ympev.2018.09.002}, pmid = {30195476}, issn = {1095-9513}, abstract = {Organellar genomes may shed light on complicated patterns of plant evolution at inter- and intraspecies level. Primary structure of plastid genomes sequenced in this study and taken from public databases was characterised and compared in 22 diverse, mostly wild representatives of the genus Pisum (peas). Phylogenetic trees reconstructed via Bayesian approach on the basis of entire plastid genomes resembled those reconstructed on the basis of a nuclear gene His5 coding for a minor histone H1 subtype. They reveal Pisum fulvum as an early divergence of the genus but do not support other taxonomical subdivisions. The positions of three accessions, classified as P. sativum subsp. elatius (the wild subspecies of the common pea), appeared quite unexpected. On the entire plastid genome tree, two accessions, from the Black Sea area of Turkey and Georgia, clustered with representatives of another species, P. fulvum, while the other, from Greece, was the first divergence of the P. sativum branch. We suppose these unusual plastid genomes to be ancient lineages ascending to a 'missing link' between P. fulvum and P. sativum, represented by accession Pe 013 from Turkey. Accessions with common pea appearance but deeply diverged plastids could occur through occasional crossing of diverged pea lines in the past and biparental plastid inheritance, both events being possible in peas.}, } @article {pmid30195475, year = {2018}, author = {Schneider, SA and Okusu, A and Normark, BB}, title = {Molecular phylogenetics of Aspidiotini armored scale insects (Hemiptera: Diaspididae) reveals rampant paraphyly, curious species radiations, and multiple origins of association with Melissotarsus ants (Hymenoptera: Formicidae).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {291-303}, doi = {10.1016/j.ympev.2018.09.003}, pmid = {30195475}, issn = {1095-9513}, abstract = {The armored scale insect tribe Aspidiotini comprises many pest species that are globally invasive and economically damaging. The taxonomy of scale insects is based almost solely upon morphological characters of adult females, and little prior work has been done to test the classification of aspidiotines against molecular evidence. To address these concerns, we reconstruct a molecular phylogeny for aspidiotine armored scales that expands greatly upon taxonomic and character representations from previous studies. Our dataset includes 127 species (356 terminal taxa) and four gene regions: 28S, EF-1α, COI-COII, and CAD. Nearly 50% of the species treated are identified as pests and several more may represent emerging pests. Phylogenetic data were analyzed in a Bayesian framework using MC3 iterations. The majority of sampled aspidiotine genera are not monophyletic as currently defined. Monophyly constraints for 'worst offenders' were imposed on the phylogeny and stepping-stone MCMC was performed to calculate marginal likelihood scores. Comparisons of marginal likelihoods from runs with constrained vs. informative priors support the interpretation that pest-rich genera are not monophyletic. We use character mapping to illustrate signal and convergence for selected traits that have been used to define or recognize genera and evaluate consistency and retention indices for these traits. The phylogeny illustrates a pervasive pattern in which extremely polyphagous pests - typically having large populations and wide geographical distributions - are frequently intertwined with range-limited specialists on the phylogeny. Finally, the phylogeny recovers three origins of ant association among the Aspidiotini. The history of ant/diaspidid symbioses involves periods of sustained partner fidelity, spanning multiple speciation events, which have been punctuated by opportunistic switches to novel partners.}, } @article {pmid30195442, year = {2018}, author = {Frouin, M and Lahaye, C and Valladas, H and Higham, T and Delagnes, A and Mercier, N}, title = {Corrigendum to "Dating the Middle Palaeolithic deposits of La Quina Amont (Charente, France) using luminescence methods" [Journal of Human Evolution 109 (2017) 30-45].}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {140-141}, doi = {10.1016/j.jhevol.2018.05.003}, pmid = {30195442}, issn = {1095-8606}, } @article {pmid30195150, year = {2018}, author = {Sharma, A and Gilbert, JA}, title = {Microbial exposure and human health.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {79-87}, doi = {10.1016/j.mib.2018.08.003}, pmid = {30195150}, issn = {1879-0364}, abstract = {The human body comprises of micro-ecosystem made up of trillions of microbes (i.e. bacteria, archaea, fungi, protists and viruses). The total microbial gene content, which is referred to as the human microbiome, is fundamental to human physiology and immunity. There exists an intricate relationship between the surrounding microbial world (i.e. the environment) and the endogenous human microbiome, mediated by the immune system. Disrupting this relationship can a profound effect on human health and disease. Understanding how microbial exposure influences immune response and the feedback on endogenous microbial metabolic activity could have profound implications for the development of novel microbial therapeutics. The term 'microbial exposure' is used generally to refer to exogenous environmental microbial interaction, while 'exposome' accounts for both the environmental exposures and the impact of lifestyle-associated microbial impacts, such as diet influences on endogenous microbial metabolism. In this review, we focus on how environment and lifestyle-associated microbial exposures shape the human immune system and microbiome, and how the resulting changes can shape human health, especially during critical developmental windows, that is prenatal, postnatal and adult. We conclude this review by proposing approaches to characterize the microbial exposome so as to accelerate the development of a precision microbial therapeutics for both practical and clinical intervention.}, } @article {pmid30195040, year = {2018}, author = {Floden, A and Schilling, EE}, title = {Using phylogenomics to reconstruct phylogenetic relationships within tribe Polygonateae (Asparagaceae), with a special focus on Polygonatum.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {202-213}, doi = {10.1016/j.ympev.2018.08.017}, pmid = {30195040}, issn = {1095-9513}, abstract = {Polygonatum is a widespread temperate genus with approximately 75 species centered in the Eastern Himalaya and Indo-Burma biodiversity hotspots. A complete assessment of the remarkable diversity of Polygonatum in these areas requires an accurate circumscription of the genus, as well as a clear understanding of generic and infrageneric relationships, both of which have been problematic in the past. In this study, we reconstruct phylogenetic relationships within Polygonatum and test its monophyly using a phylogenomic approach. For that, we built a comprehensive dataset that includes complete or nearly-complete plastid genomes of 19 species of Polygonatum, one of Disporopsis, and four of Heteropolygonatum. Their plastid genomes do not present any major structural differences and range from 153,821 to 155,580 bp in length. Molecular phylogenetic analyses of the chloroplast coding regions indicate that Polygonatum and Heteropolygonatum are monophyletic, providing support for their recognition as distinct genera and corroborating recent adjustments of their circumscriptions. An expanded analysis with higher species sampling using the petA-psbJ plastid gene region combined with the nuclear ribosomal ITS provided support for the recognition of three distinct sections within Polygonatum. These same sections are further supported by chromosome data: Polygonatum sect. Sibirica (x = 12); Polygonatum sect. Polygonatum (x = 9-11); and, Polygonatum sect. Verticillata (x = 13-15). Populations of P. multiflorum from northwestern Himalaya are here shown to be best treated as a separate taxon, P. govanianum. Furthermore, P. verticillatum is shown to be polyphyletic, indicating that it represents a species-complex that includes multiple Asiatic species. Despite that, additional studies are still needed until the proper nomenclatural adjustments can be made.}, } @article {pmid30195039, year = {2018}, author = {Near, TJ and MacGuigan, DJ and Parker, E and Struthers, CD and Jones, CD and Dornburg, A}, title = {Phylogenetic analysis of Antarctic notothenioids illuminates the utility of RADseq for resolving Cenozoic adaptive radiations.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {268-279}, doi = {10.1016/j.ympev.2018.09.001}, pmid = {30195039}, issn = {1095-9513}, abstract = {Notothenioids are a clade of ∼120 species of marine fishes distributed in extreme southern hemisphere temperate near-shore habitats and in the Southern Ocean surrounding Antarctica. Over the past 25 years, molecular and morphological approaches have redefined hypotheses of relationships among notothenioid lineages as well as their relationships among major lineages of percomorph teleosts. These phylogenies provide a basis for investigation of mechanisms of evolutionary diversification within the clade and have enhanced our understanding of the notothenioid adaptive radiation. Despite extensive efforts, there remain several questions concerning the phylogeny of notothenioids. In this study, we deploy DNA sequences of ∼100,000 loci obtained using RADseq to investigate the phylogenetic relationships of notothenioids and to assess the utility of RADseq loci for lineages that exhibit divergence times ranging from the Paleogene to the Quaternary. The notothenioid phylogenies inferred from the RADseq loci provide unparalleled resolution and node support for several long-standing problems including, (1) relationships among species of Trematomus, (2) resolution of Indonotothenia cyanobrancha as the sister lineage of Trematomus, (3) the deep paraphyly of Nototheniidae, (4) the paraphyly of Lepidonotothen s.l., (5) paraphyly of Artedidraco, and 6) the monophyly of the Bathydraconidae. Assessment of site rates demonstrates that RADseq loci are similar to mtDNA protein coding genes and exhibit peak phylogenetic informativeness at the time interval during which the major Antarctic notothenioid lineages originated and diversified. In addition to providing a well-resolved phylogenetic hypothesis for notothenioids, our analyses quantify the predicted utility of RADseq loci for Cenozoic phylogenetic inferences.}, } @article {pmid30194919, year = {2018}, author = {Kersbergen, A and Best, SA and Dworkin, S and Ah-Cann, C and de Vries, ME and Asselin-Labat, ML and Ritchie, ME and Jane, SM and Sutherland, KD}, title = {Lung morphogenesis is orchestrated through Grainyhead-like 2 (Grhl2) transcriptional programs.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {1-9}, doi = {10.1016/j.ydbio.2018.09.002}, pmid = {30194919}, issn = {1095-564X}, mesh = {Alveolar Epithelial Cells/metabolism/*physiology ; Animals ; Cell Differentiation ; DNA-Binding Proteins/metabolism ; Down-Regulation ; Epithelium/metabolism ; Gene Expression Profiling ; Lung/embryology/metabolism/physiology ; Mice/embryology ; Respiratory Function Tests/methods ; SOX9 Transcription Factor ; Saccule and Utricle/metabolism ; Transcription Factors/*metabolism/*physiology ; }, abstract = {The highly conserved transcription factor Grainyhead-like 2 (Grhl2) exhibits a dynamic expression pattern in lung epithelium throughout embryonic development. Using a conditional gene targeting approach to delete Grhl2 in the developing lung epithelium, our results demonstrate that Grhl2 plays multiple roles in lung morphogenesis that are essential for respiratory function. Loss of Grhl2 leads to impaired ciliated cell differentiation and perturbed formation of terminal saccules. Critically, a substantial increase in Sox9-positive distal tip progenitor cells was observed following loss of Grhl2, suggesting that Grhl2 plays an important role in branching morphogenesis. Gene transcription profiling of Grhl2-deficient lung epithelial cells revealed a significant down regulation of Elf5, a member of the Ets family of transcription factors. Furthermore, ChIP and comparative genomic analyzes confirmed that Elf5 is a direct transcriptional target of Grhl2. Taken together, these results support the hypothesis that Grhl2 controls normal lung morphogenesis by tightly regulating the activity of distal tip progenitor cells.}, } @article {pmid30194777, year = {2018}, author = {Peccoud, J and Pleydell, DRJ and Sauvion, N}, title = {A framework for estimating the effects of sequential reproductive barriers: Implementation using Bayesian models with field data from cryptic species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2503-2512}, doi = {10.1111/evo.13595}, pmid = {30194777}, issn = {1558-5646}, support = {SDIPS//INRA/ ; }, abstract = {Determining how reproductive barriers modulate gene flow between populations represents a major step toward understanding the factors shaping the course of speciation. Although many indices quantifying reproductive isolation (RI) have been proposed, they do not permit the quantification of cross-direction-specific RI under varying species frequencies and over arbitrary sequences of barriers. Furthermore, techniques quantifying associated uncertainties are lacking, and statistical methods unrelated to biological process are still preferred for obtaining confidence intervals and P-values. To address these shortcomings, we provide new RI indices that model changes in gene flow for both directions of hybridization, and we implement them in a Bayesian model. We use this model to quantify RI between two species of the psyllid Cacopsylla pruni based on field genotypic data for mating individuals, inseminated spermatophores and progeny. The results showed that preinsemination isolation was strong, mildly asymmetric, and indistinguishably different between study sites despite large differences in species frequencies; that postinsemination isolation strongly affected the more common hybrid type; and that cumulative isolation was close to complete. In the light of these results, we discuss how these developments can strengthen comparative RI studies.}, } @article {pmid30194757, year = {2018}, author = {Zuellig, MP and Sweigart, AL}, title = {A two-locus hybrid incompatibility is widespread, polymorphic, and active in natural populations of Mimulus.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2394-2405}, doi = {10.1111/evo.13596}, pmid = {30194757}, issn = {1558-5646}, support = {DEB-1350935//Directorate for Biological Sciences/ ; T32_GM007103//National Institute of General Medical Sciences/ ; }, abstract = {Reproductive isolation, which is essential for the maintenance of species in sympatry, is often incomplete between closely related species. In these taxa, reproductive barriers must evolve within species, without being degraded by ongoing gene flow. To better understand this dynamic, we investigated the frequency and geographic distribution of alleles underlying a two-locus, hybrid lethality system between naturally hybridizing species of monkeyflower (Mimulus guttatus and M. nasutus). We found that M. guttatus typically carries hybrid lethality alleles at one locus (hl13) and M. nasutus typically carries hybrid lethality alleles at the other locus (hl14). As a result, natural hybrids carry incompatible alleles at both loci, and express hybrid lethality in later generations. We also discovered considerable polymorphism at both hl13 and hl14 within both species. For M. guttatus, polymorphism at both loci occurs within populations, meaning that incompatible allele pairings likely arise through intraspecific gene flow. Genetic variation at markers linked to hl13 and hl14 suggest that introgression from M. nasutus is the primary driver of this polymorphism within M. guttatus. Additionally, patterns of introgression at the two hybrid lethality loci suggest that natural selection eliminates incompatible allele pairings, suggesting that even weak reproductive barriers might promote genomic divergence between species.}, } @article {pmid30194754, year = {2018}, author = {Peters, MAE and Weis, AE}, title = {Selection for pollen competitive ability in mixed-mating systems.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2513-2536}, doi = {10.1111/evo.13597}, pmid = {30194754}, issn = {1558-5646}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {Coexpression of genes in plant sporophytes and gametophytes allows correlated gametic and sporophytic selection. Theory predicts that, under outcrossing, an allele conferring greater pollen competitive ability should fix within a population unless antagonistic pleiotropy with the sporophyte stage is strong. However, under strong selfing, pollen competitiveness is immaterial as superior and inferior competitors are deposited on opposite stigmas, producing assortative competition. Because many plant species have mixed-mating systems, selfing should be critical in the spread and maintenance of pollen-expressed genes affecting competitiveness. We present two one-locus, two-allele population genetic models for the evolution of a locus controlling pleiotropic antagonism between pollen competitiveness and diploid fitness. Analytical solutions provide minimum and maximum selfing rates allowing invasion of alleles with greater diploid and haploid fitness, respectively. Further, polymorphism is only maintained when diploid selection is recessive. Fixation of the allele conferring greater pollen competitiveness may be prevented, even with weak sporophytic counterselection, with sufficiently high selfing. Finally, selfing expands and limits the range of haploid-diploid selection coefficients allowing polymorphism, depending on dominance and selfing mode.}, } @article {pmid30194479, year = {2018}, author = {Zhang, Y and Gao, X and Wang, S and Zhu, C and Li, R and Shen, Q}, title = {Application of Bacillus velezensis NJAU-Z9 Enhanced Plant Growth Associated with Efficient Rhizospheric Colonization Monitored by qPCR with Primers Designed from the Whole Genome Sequence.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1574-1583}, pmid = {30194479}, issn = {1432-0991}, support = {2017YFD0200805, 2016YFD0800605 and 2016YFE0101100//The National Key Research and Development Program of China/ ; BY2016077-05//The Scientific and technological projects of Jiangsu, China/ ; BK20160710 and BK20150059//The Natural Science Foundation of Jiangsu/ ; PAPD//The Priority Academic Program Development of the Jiangsu Higher Education Institutions/ ; B12009//The 111 project/ ; PPZY2015A061//Top-notch Academic Programs Project of Jiangsu Higher Education Institution/ ; }, mesh = {Bacillus/*genetics ; Biomass ; DNA Primers/*genetics ; Plant Development/*genetics ; Plant Roots/*microbiology ; Real-Time Polymerase Chain Reaction/methods ; Rhizosphere ; Soil ; Soil Microbiology ; Whole Genome Sequencing/methods ; }, abstract = {Plant growth-promoting rhizobacteria (PGPR) have been reported to influence plant growth, yield, and nutrient uptake by an array of mechanisms. Uncovering the behavioral dynamics of PGPR is one of the most important issues necessary for understanding their functional performances. In this study, strain NJAU-Z9 which was found to possess complex functions and efficient rhizospheric colonization ability was selected from plenty of bacterial strains isolated randomly from the pepper rhizosphere soil and identified as Bacillus velezensis. Repeated seedling nursing tests performed absolute growth-promoting advantage for the novel isolated strain. After that, primers for the quantitative detection were designed based on its whole genome sequence (WGS), and a real-time PCR method was utilized to explore strategies for monitoring the strain in natural soil and in the pepper rhizosphere. Results showed based on the whole genome, two primers were identified as NJAU-Z9-specific quantitative PCR primers. Two seasonal pot experiments demonstrated that strain NJAU-Z9 effectively colonized the rhizosphere measured by the novel abundance detecting strategy, improved plant growth, and showed a positive correlation between bacterial number and biomass. This study offers a strategy based on a real-time PCR method for directly monitoring B. velezensis strain NJAU-Z9 in the soil and the rhizosphere and provides a reference for the quantitative study of other PGPR strains based on WGSs.}, } @article {pmid30194403, year = {2018}, author = {Rokas, A and Wisecaver, JH and Lind, AL}, title = {The birth, evolution and death of metabolic gene clusters in fungi.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {731-744}, doi = {10.1038/s41579-018-0075-3}, pmid = {30194403}, issn = {1740-1534}, abstract = {Fungi contain a remarkable diversity of both primary and secondary metabolic pathways involved in ecologically specialized or accessory functions. Genes in these pathways are frequently physically linked on fungal chromosomes, forming metabolic gene clusters (MGCs). In this Review, we describe the diversity in the structure and content of fungal MGCs, their population-level and species-level variation, the evolutionary mechanisms that underlie their formation, maintenance and decay, and their ecological and evolutionary impact on fungal populations. We also discuss MGCs from other eukaryotes and the reasons for their preponderance in fungi. Improved knowledge of the evolutionary life cycle of MGCs will advance our understanding of the ecology of specialized metabolism and of the interplay between the lifestyle of an organism and genome architecture.}, } @article {pmid30194368, year = {2018}, author = {Zaidi, M and Cardozo, CP}, title = {Receptor becomes a ligand to control bone remodelling.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {180-181}, doi = {10.1038/d41586-018-05960-x}, pmid = {30194368}, issn = {1476-4687}, } @article {pmid30194367, year = {2018}, author = {Mayr, C}, title = {Protein complexes assemble as they are being made.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {186-187}, doi = {10.1038/d41586-018-05905-4}, pmid = {30194367}, issn = {1476-4687}, } @article {pmid30194366, year = {2018}, author = {Stolz, A and Dikic, I}, title = {Elusive mitochondrial connection to inflammation uncovered.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {185-186}, doi = {10.1038/d41586-018-05988-z}, pmid = {30194366}, issn = {1476-4687}, mesh = {Humans ; *Inflammation ; *Mitochondria ; Parkinson Disease ; Protein Kinases ; }, } @article {pmid30194345, year = {2018}, author = {Carlton, JM}, title = {Publisher Correction: Evolution of human malaria.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1188}, doi = {10.1038/s41564-018-0249-9}, pmid = {30194345}, issn = {2058-5276}, support = {U19 AI089676/AI/NIAID NIH HHS/United States ; }, abstract = {In the version of this News & Views originally published, the caption of Fig. 1 failed to acknowledge that the figure was adapted from Fig. 1 of E. J. Scully, U. Kanjee & M. T. Duraisingh Curr. Opin. Microbiol. 40, 21-31; 2017. This omission failed to recognize the scholarly work of Erik J. Scully, Usheer Kanjee and Manoj T. Duraisingh in generating the original version of the figure. Figure 1 has now been replaced in the News & Views with a new figure and caption (see below) describing the status of genome sequencing for primate-infecting species in the Plasmodium genus, and the paper by Scully et al. has been cited in the caption and added to the reference list at number 12. The publisher and editors apologize to the authors of the original figure, the author of the News & Views, and our readers for this mistake.}, } @article {pmid30194237, year = {2018}, author = {Wong, F and Dutta, A and Chowdhury, D and Gunawardena, J}, title = {Structural conditions on complex networks for the Michaelis-Menten input-output response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9738-9743}, pmid = {30194237}, issn = {1091-6490}, abstract = {The Michaelis-Menten (MM) fundamental formula describes how the rate of enzyme catalysis depends on substrate concentration. The familiar hyperbolic relationship was derived by timescale separation for a network of three reactions. The same formula has subsequently been found to describe steady-state input-output responses in many biological contexts, including single-molecule enzyme kinetics, gene regulation, transcription, translation, and force generation. Previous attempts to explain its ubiquity have been limited to networks with regular structure or simplifying parametric assumptions. Here, we exploit the graph-based linear framework for timescale separation to derive general structural conditions under which the MM formula arises. The conditions require a partition of the graph into two parts, akin to a "coarse graining" into the original MM graph, and constraints on where and how the input variable occurs. Other features of the graph, including the numerical values of parameters, can remain arbitrary, thereby explaining the formula's ubiquity. For systems at thermodynamic equilibrium, we derive a necessary and sufficient condition. For systems away from thermodynamic equilibrium, especially those with irreversible reactions, distinct structural conditions arise and a general characterization remains open. Nevertheless, our results accommodate, in much greater generality, all examples known to us in the literature.}, } @article {pmid30194236, year = {2018}, author = {Ravindran, S}, title = {Profile of Yuval Peres.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9646-9648}, pmid = {30194236}, issn = {1091-6490}, } @article {pmid30194235, year = {2018}, author = {Li, X and Edwards, M and Swaney, KF and Singh, N and Bhattacharya, S and Borleis, J and Long, Y and Iglesias, PA and Chen, J and Devreotes, PN}, title = {Mutually inhibitory Ras-PI(3,4)P2 feedback loops mediate cell migration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9125-E9134}, pmid = {30194235}, issn = {1091-6490}, support = {R01 GM089771/GM/NIGMS NIH HHS/United States ; R35 GM118177/GM/NIGMS NIH HHS/United States ; S10 OD016374/OD/NIH HHS/United States ; S10 OD023548/OD/NIH HHS/United States ; }, mesh = {Cell Membrane/genetics/*metabolism ; Dictyostelium/genetics/*metabolism ; Phosphatidylinositol Phosphates/genetics/*metabolism ; Protozoan Proteins/genetics/*metabolism ; Signal Transduction/*physiology ; ras Proteins/genetics/*metabolism ; }, abstract = {Signal transduction and cytoskeleton networks in a wide variety of cells display excitability, but the mechanisms are poorly understood. Here, we show that during random migration and in response to chemoattractants, cells maintain complementary spatial and temporal distributions of Ras activity and phosphatidylinositol (3,4)-bisphosphate [PI(3,4)P2]. In addition, depletion of PI(3,4)P2 by disruption of the 5-phosphatase, Dd5P4, or by recruitment of 4-phosphatase INPP4B to the plasma membrane, leads to elevated Ras activity, cell spreading, and altered migratory behavior. Furthermore, RasGAP2 and RapGAP3 bind to PI(3,4)P2, and the phenotypes of cells lacking these genes mimic those with low PI(3,4)P2 levels, providing a molecular mechanism. These findings suggest that Ras activity drives PI(3,4)P2 down, causing the PI(3,4)P2-binding GAPs to dissociate from the membrane, further activating Ras, completing a positive-feedback loop essential for excitability. Consistently, a computational model incorporating such a feedback loop in an excitable network model accurately simulates the dynamic distributions of active Ras and PI(3,4)P2 as well as cell migratory behavior. The mutually inhibitory Ras-PI(3,4)P2 mechanisms we uncovered here provide a framework for Ras regulation that may play a key role in many physiological processes.}, } @article {pmid30194234, year = {2018}, author = {Guryev, EL and Volodina, NO and Shilyagina, NY and Gudkov, SV and Balalaeva, IV and Volovetskiy, AB and Lyubeshkin, AV and Sen', AV and Ermilov, SA and Vodeneev, VA and Petrov, RV and Zvyagin, AV and Alferov, ZI and Deyev, SM}, title = {Radioactive (90Y) upconversion nanoparticles conjugated with recombinant targeted toxin for synergistic nanotheranostics of cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9690-9695}, pmid = {30194234}, issn = {1091-6490}, mesh = {Adenocarcinoma/therapy ; Ankyrin Repeat ; Breast Neoplasms/therapy ; Cell Line, Tumor ; Drug Delivery Systems/*methods ; Endotoxins/*therapeutic use ; Female ; Humans ; Nanoparticles/*therapeutic use ; Nanotechnology/*methods ; Neoplasms/diagnostic imaging/*therapy ; Pseudomonas aeruginosa ; Radionuclide Imaging/methods ; Radiotherapy/*methods ; Receptor, ErbB-2/metabolism ; Recombinant Proteins ; Yttrium Radioisotopes/therapeutic use ; }, abstract = {We report combined therapy using upconversion nanoparticles (UCNP) coupled to two therapeutic agents: beta-emitting radionuclide yttrium-90 (90Y) fractionally substituting yttrium in UCNP, and a fragment of the exotoxin A derived from Pseudomonas aeruginosa genetically fused with a targeting designed ankyrin repeat protein (DARPin) specific to HER2 receptors. The resultant hybrid complex UCNP-R-T was tested using human breast adenocarcinoma cells SK-BR-3 overexpressing HER2 receptors and immunodeficient mice, bearing HER2-positive xenograft tumors. The photophysical properties of UCNPs enabled background-free imaging of the UCNP-R-T distribution in cells and animals. Specific binding and uptake of UCNP complexes in SK-BR-3 cells was observed, with separate 90Y- and PE40-induced cytotoxic effects characterized by IC50 140 μg/mL (UCNP-R) and 5.2 μg/mL (UCNP-T), respectively. When both therapeutic agents were combined into UCNP-R-T, the synergetic effect increased markedly, ∼2200-fold, resulting in IC50 = 0.0024 μg/mL. The combined therapy with UCNP-R-T was demonstrated in vivo.}, } @article {pmid30194233, year = {2018}, author = {Wei, Q and Kais, S and Yasuike, T and Herschbach, D}, title = {Pendular alignment and strong chemical binding are induced in helium dimer molecules by intense laser fields.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9058-E9066}, pmid = {30194233}, issn = {1091-6490}, abstract = {Intense pulsed-laser fields have provided means to both induce spatial alignment of molecules and enhance strength of chemical bonds. The duration of the laser field typically ranges from hundreds of picoseconds to a few femtoseconds. Accordingly, the induced "laser-dressed" properties can be adiabatic, existing only during the pulse, or nonadiabatic, persisting into the subsequent field-free domain. We exemplify these aspects by treating the helium dimer, in its ground [Formula: see text] and first excited [Formula: see text] electronic states. The ground-state dimer when field-free is barely bound, so very responsive to electric fields. We examine two laser realms, designated (I) "intrusive" and (II) "impelling." I employs intense nonresonant laser fields, not strong enough to dislodge electrons, yet interact with the dimer polarizability to induce binding and pendular states in which the dimer axis librates about the electric field direction. II employs superintense high-frequency fields that impel the electrons to undergo quiver oscillations, which interact with the intrinsic Coulomb forces to form an effective binding potential. The dimer bond then becomes much stronger. For I, we map laser-induced pendular alignment within the X state, which is absent for the field-free dimer. For II, we evaluate vibronic transitions from the X to A states, governed by the amplitude of the quiver oscillations.}, } @article {pmid30194232, year = {2018}, author = {Häusler, D and Häusser-Kinzel, S and Feldmann, L and Torke, S and Lepennetier, G and Bernard, CCA and Zamvil, SS and Brück, W and Lehmann-Horn, K and Weber, MS}, title = {Functional characterization of reappearing B cells after anti-CD20 treatment of CNS autoimmune disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9773-9778}, pmid = {30194232}, issn = {1091-6490}, mesh = {Animals ; Antibodies, Monoclonal/immunology/therapeutic use ; Antigens, CD20/*immunology ; B-Lymphocytes/*immunology ; Bone Marrow Cells/immunology ; Encephalomyelitis, Autoimmune, Experimental/*immunology/therapy ; Lymph Nodes/cytology/immunology ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/immunology ; Spleen/cytology/immunology ; }, abstract = {The anti-CD20 antibody ocrelizumab, approved for treatment of multiple sclerosis, leads to rapid elimination of B cells from the blood. The extent of B cell depletion and kinetics of their recovery in different immune compartments is largely unknown. Here, we studied how anti-CD20 treatment influences B cells in bone marrow, blood, lymph nodes, and spleen in models of experimental autoimmune encephalomyelitis (EAE). Anti-CD20 reduced mature B cells in all compartments examined, although a subpopulation of antigen-experienced B cells persisted in splenic follicles. Upon treatment cessation, CD20+ B cells simultaneously repopulated in bone marrow and spleen before their reappearance in blood. In EAE induced by native myelin oligodendrocyte glycoprotein (MOG), a model in which B cells are activated, B cell recovery was characterized by expansion of mature, differentiated cells containing a high frequency of myelin-reactive B cells with restricted B cell receptor gene diversity. Those B cells served as efficient antigen-presenting cells (APCs) for activation of myelin-specific T cells. In MOG peptide-induced EAE, a purely T cell-mediated model that does not require B cells, in contrast, reconstituting B cells exhibited a naive phenotype without efficient APC capacity. Our results demonstrate that distinct subpopulations of B cells differ in their sensitivity to anti-CD20 treatment and suggest that differentiated B cells persisting in secondary lymphoid organs contribute to the recovering B cell pool.}, } @article {pmid30194231, year = {2018}, author = {De Vico, L and Anda, A and Osipov, VA and Madsen, AØ and Hansen, T}, title = {Macrocycle ring deformation as the secondary design principle for light-harvesting complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9051-E9057}, pmid = {30194231}, issn = {1091-6490}, mesh = {Alphaproteobacteria/*chemistry/metabolism ; Bacterial Proteins/*chemistry/metabolism ; Bacteriochlorophylls/*chemistry/metabolism ; Light-Harvesting Protein Complexes/*chemistry/metabolism ; Photosynthesis/physiology ; }, abstract = {Natural light-harvesting is performed by pigment-protein complexes, which collect and funnel the solar energy at the start of photosynthesis. The identity and arrangement of pigments largely define the absorption spectrum of the antenna complex, which is further regulated by a palette of structural factors. Small alterations are induced by pigment-protein interactions. In light-harvesting systems 2 and 3 from Rhodoblastus acidophilus, the pigments are arranged identically, yet the former has an absorption peak at 850 nm that is blue-shifted to 820 nm in the latter. While the shift has previously been attributed to the removal of hydrogen bonds, which brings changes in the acetyl moiety of the bacteriochlorophyll, recent work has shown that other mechanisms are also present. Using computational and modeling tools on the corresponding crystal structures, we reach a different conclusion: The most critical factor for the shift is the curvature of the macrocycle ring. The bending of the planar part of the pigment is identified as the second-most important design principle for the function of pigment-protein complexes-a finding that can inspire the design of novel artificial systems.}, } @article {pmid30194230, year = {2018}, author = {Holden, N and Peres, Y and Zhai, A}, title = {Gravitational allocation on the sphere.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9666-9671}, pmid = {30194230}, issn = {1091-6490}, abstract = {Given a collection L of n points on a sphere [Formula: see text] of surface area n, a fair allocation is a partition of the sphere into n parts each of area 1, and each is associated with a distinct point of L. We show that, if the n points are chosen uniformly at random and if the partition is defined by a certain "gravitational" potential, then the expected distance between a point on the sphere and the associated point of L is [Formula: see text] We use our result to define a matching between two collections of n independent and uniform points on the sphere and prove that the expected distance between a pair of matched points is [Formula: see text], which is optimal by a result of Ajtai, Komlós, and Tusnády.}, } @article {pmid30194229, year = {2018}, author = {Nelson, CA and Wilen, CB and Dai, YN and Orchard, RC and Kim, AS and Stegeman, RA and Hsieh, LL and Smith, TJ and Virgin, HW and Fremont, DH}, title = {Structural basis for murine norovirus engagement of bile acids and the CD300lf receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9201-E9210}, pmid = {30194229}, issn = {1091-6490}, support = {U19 AI109725/AI/NIAID NIH HHS/United States ; R01 AI127552/AI/NIAID NIH HHS/United States ; K99 DK116666/DK/NIDDK NIH HHS/United States ; K08 AI128043/AI/NIAID NIH HHS/United States ; HHSN272201700060C/AI/NIAID NIH HHS/United States ; R01 GM030498/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/*chemistry/metabolism ; Caliciviridae Infections ; Cell Line ; Cryoelectron Microscopy ; Mice ; *Molecular Docking Simulation ; Mutation ; Norovirus/*chemistry/genetics/metabolism ; Protein Domains ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Receptors, Immunologic/*chemistry/genetics/metabolism ; Virion/*chemistry/genetics/metabolism ; }, abstract = {Murine norovirus (MNoV) is closely related to human norovirus (HNoV), an infectious agent responsible for acute gastroenteritis worldwide. Here we report the X-ray crystal structure of the dimeric MNoV VP1 protruding (P) domain in complex with its cellular receptor CD300lf. CD300lf binds the P domain with a 2:2 stoichiometry, engaging a cleft between the AB and DE loops of the P2 subdomain at a site that overlaps the epitopes of neutralizing antibodies. We also identify that bile acids are cofactors enhancing MNoV cell-binding and infectivity. Structures of CD300lf-P domain in complex with glycochenodeoxycholic acid (GCDCA) and lithocholic acid (LCA) reveal two bile acid binding sites at the P domain dimer interface distant from receptor binding sites. The structural determinants for receptor and bile acid binding are supported by numerous biophysical assays utilizing interface residue mutations. We find that the monomeric affinity of CD300lf for the P domain is low and is divalent cation dependent. We have also determined the crystal structure of CD300lf in complex with phosphocholine, revealing that MNoV engages its receptor in a manner mimicking host ligands including similar metal coordination. Docking of the cocomplex structures onto a cryo-EM-derived model of MNoV suggests that each virion can make multiple CD300lf engagements, and thus, infection may be driven by the avidity of cell surface clustered CD300lf. These studies identify multiple potential modulators of norovirus infection that may act to regulate the interaction between the viral capsid P domain and its cognate cellular receptor.}, } @article {pmid30193960, year = {2018}, author = {Balloux, F and Brønstad Brynildsrud, O and van Dorp, L and Shaw, LP and Chen, H and Harris, KA and Wang, H and Eldholm, V}, title = {From Theory to Practice: Translating Whole-Genome Sequencing (WGS) into the Clinic.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {1035-1048}, pmid = {30193960}, issn = {1878-4380}, abstract = {Hospitals worldwide are facing an increasing incidence of hard-to-treat infections. Limiting infections and providing patients with optimal drug regimens require timely strain identification as well as virulence and drug-resistance profiling. Additionally, prophylactic interventions based on the identification of environmental sources of recurrent infections (e.g., contaminated sinks) and reconstruction of transmission chains (i.e., who infected whom) could help to reduce the incidence of nosocomial infections. WGS could hold the key to solving these issues. However, uptake in the clinic has been slow. Some major scientific and logistical challenges need to be solved before WGS fulfils its potential in clinical microbial diagnostics. In this review we identify major bottlenecks that need to be resolved for WGS to routinely inform clinical intervention and discuss possible solutions.}, } @article {pmid30193959, year = {2018}, author = {Porter, NT and Luis, AS and Martens, EC}, title = {Bacteroides thetaiotaomicron.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {966-967}, doi = {10.1016/j.tim.2018.08.005}, pmid = {30193959}, issn = {1878-4380}, abstract = {This infographic on Bacteroides thetaiotaomicron (Bt) explores the ability of this microbe to digest a broad array of complex carbohydrates, alter its surface features, and its emerging role in gastrointestinal diseases. The infographic of Bacteroides thetaiotaomicron (Bt) illustrates two key facets of its symbiotic lifestyle in the human gut: a broad ability to digest dietary fiber polysaccharides and host glycans, and a dynamic cell-surface architecture that promotes both interactions with and evasion of the host immune system. The starch-utilization system (Sus) is a cell-surface and periplasmic system involved in starch cleavage and transport. Over 80 additional Sus-like systems utilize substrates ranging from host glycans to plant cell wall pectins. Bt has evolved intricate strategies to interact with other microbes or its host, including modification of its surface. Some nutrient utilization pathways select for or directly trigger changes in capsular polysaccharide (CPS) expression. Like other fermentative members of the gut microbiome, Bt produces host absorbable short-chain and organic acids, which can all be absorbed by the host as a source of energy.}, } @article {pmid30193862, year = {2018}, author = {Licht, A and Bommer, M and Werther, T and Neumann, K and Hobe, C and Schneider, E}, title = {Structural and functional characterization of a maltose/maltodextrin ABC transporter comprising a single solute binding domain (MalE) fused to the transmembrane subunit MalF.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.08.006}, pmid = {30193862}, issn = {1769-7123}, abstract = {Canonical ATP-binding cassette import systems rely on extracellular substrate binding proteins (SBP) for function. In gram-negative bacteria, SBPs are usually freely diffusible in the periplasm and, where studied, exist in excess over their cognate transporters. However, in vitro studies with the maltose transporter of Escherichia coli (MalFGK2) have demonstrated that mechanistically one copy of its SBP (MalE) per transport complex is sufficient for activity. To address whether such a condition is physiologically relevant, we have characterized a homolog of the E. coli system from the gram-negative bacterium Bdellovibrio bacteriovorus which has a single copy of a maltose binding domain fused to the MalF subunit. Both transporters share substrate specificity for maltose and linear maltodextrins. Specific ATPase and transport activities of the B. bacteriovorus transporter were comparable to those of the E. coli system assayed at a 1:1 M ratio of MalE to the transport complex. While MalEEc was able to additionally increase ATPase activity of MalFGK2Bb, the isolated MalE domain of B. bacteriovorus failed to stimulate the E. coli system. Strikingly, interactions of the MalE domain with the transmembrane subunits during the transport cycle as studied by site-specific cross-linking were found to differ from those observed for E. coli MalE-FGK2.}, } @article {pmid30193787, year = {2018}, author = {Fischer, RS and Lam, PY and Huttenlocher, A and Waterman, CM}, title = {Filopodia and focal adhesions: An integrated system driving branching morphogenesis in neuronal pathfinding and angiogenesis.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.08.015}, pmid = {30193787}, issn = {1095-564X}, abstract = {Single cell branching during development in vertebrates is typified by neuronal branching to form neurites and vascular branches formed by sprouting angiogenesis. Neurons and endothelial tip cells possess subcellular protrusions that share many common features from the morphological to the molecular level. Both systems utilize filopodia as their cellular protrusion organelles and depend on specific integrin-mediated adhesions to the local extracellular matrix for guidance in their pathfinding. We discuss the similar molecular machineries involved in these two types of cell branch formation and use their analogy to propose a new mechanism for angiogenic filopodia function, namely as adhesion assembly sites. In support of this model we provide primary data of angiogenesis in zebrafish in vivo showing that the actin assembly factor VASP participates in both filopodia formation and adhesion assembly at the base of the filopodia, enabling forward progress of the tip cell. The use of filopodia and their associated adhesions provide a common mechanism for neuronal and endothelial pathfinding during development in response to extracellular matrix cues.}, } @article {pmid30193568, year = {2018}, author = {Couto Alves, A and Glastonbury, CA and El-Sayed Moustafa, JS and Small, KS}, title = {Fasting and time of day independently modulate circadian rhythm relevant gene expression in adipose and skin tissue.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {659}, pmid = {30193568}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; MR/L01999X/1//Medical Research Council/United Kingdom ; }, mesh = {Adipose Tissue/*metabolism ; Circadian Rhythm/*genetics ; Fasting/*physiology ; Female ; Gene-Environment Interaction ; Humans ; Middle Aged ; Organ Specificity ; Quantitative Trait Loci/genetics ; Risk Factors ; Skin/*metabolism ; Transcriptome/*physiology ; }, abstract = {BACKGROUND: Intermittent fasting and time-restricted diets are associated with lower risk biomarkers for cardio-metabolic disease. The shared mechanisms underpinning the similar physiological response to these events is not established, but circadian rhythm could be involved. Here we investigated the transcriptional response to fasting in a large cross-sectional study of adipose and skin tissue from healthy volunteers (N = 625) controlling for confounders of circadian rhythm: time of day and season.

RESULTS: We identified 367 genes in adipose and 79 in skin whose expression levels were associated (FDR < 5%) with hours of fasting conditionally independent of time of day and season, with 19 genes common to both tissues. Among these genes, we replicated 38 in human, 157 in non-human studies, and 178 are novel associations. Fasting-responsive genes were enriched for regulation of and response to circadian rhythm. We identified 99 genes in adipose and 54 genes in skin whose expression was associated to time of day; these genes were also enriched for circadian rhythm processes. In genes associated to both exposures the effect of time of day was stronger and in an opposite direction to that of hours fasted. We also investigated the relationship between fasting and genetic regulation of gene expression, including GxE eQTL analysis to identify personal responses to fasting.

CONCLUSION: This study robustly implicates circadian rhythm genes in the response to hours fasting independently of time of day, seasonality, age and BMI. We identified tissue-shared and tissue-specific differences in the transcriptional response to fasting in a large sample of healthy volunteers.}, } @article {pmid30193402, year = {2018}, author = {Miralles, A and Marin, J and Markus, D and Herrel, A and Hedges, SB and Vidal, N}, title = {Molecular evidence for the paraphyly of Scolecophidia and its evolutionary implications.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1782-1793}, doi = {10.1111/jeb.13373}, pmid = {30193402}, issn = {1420-9101}, abstract = {The phylogenetic relationships between the three main clades of worm snakes remain controversial. This question is, however, crucial to elucidate the origin of the successful snake radiation, as these burrowing and miniaturized wormlike organisms represent the earliest branching clades within the snake tree. The present molecular phylogenetic study, intended to minimize the amount of missing data, provides fully resolved inter-subfamilial relationships among Typhlopidae. It also brings robust evidence that worm snakes (Scolecophidia) are paraphyletic, with the scolecophidian family Anomalepididae recovered with strong support as sister clade to the 'typical snakes' (Alethinophidia). Ancestral state reconstructions applied to three different traits strongly associated to a burrowing life-style (scolecoidy, absence of retinal cones and microstomy) provide results in favour of a burrowing origin of snakes, and suggest that worm snakes might be the only extant fossorial representatives of the primordial snake incursion towards an underground environment.}, } @article {pmid30192637, year = {2018}, author = {Ausubel, FM}, title = {Tracing My Roots: How I Became a Plant Biologist.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {1-20}, doi = {10.1146/annurev-genet-120417-031722}, pmid = {30192637}, issn = {1545-2948}, abstract = {My trajectory to becoming a plant biologist was shaped by a complex mix of scientific, political, sociological, and personal factors. I was trained as a microbiologist and molecular biologist in the late 1960s and early 1970s, a time of political upheaval surrounding the Vietnam War. My political activism taught me to be wary of the potential misuses of scientific knowledge and to promote the positive applications of science for the benefit of society. I chose agricultural science for my postdoctoral work. Because I was not trained as a plant biologist, I devised a postdoctoral project that took advantage of my microbiological training, and I explored using genetic technologies to transfer the ability to fix nitrogen from prokaryotic nitrogen-fixing species to the model plant Arabidopsis thaliana with the ultimate goal of engineering crop plants. The invention of recombinant DNA technology greatly facilitated the cloning and manipulation of bacterial nitrogen-fixation (nif) genes, but it also forced me to consider how much genetic engineering of organisms, including human beings, is acceptable. My laboratory has additionally studied host-pathogen interactions using Arabidopsis and the nematode Caenorhabditis elegans as model hosts.}, } @article {pmid30192636, year = {2018}, author = {Birnbaum, KD}, title = {Power in Numbers: Single-Cell RNA-Seq Strategies to Dissect Complex Tissues.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {203-221}, doi = {10.1146/annurev-genet-120417-031247}, pmid = {30192636}, issn = {1545-2948}, support = {R01 GM078279/GM/NIGMS NIH HHS/United States ; }, abstract = {The growing scale and declining cost of single-cell RNA-sequencing (RNA-seq) now permit a repetition of cell sampling that increases the power to detect rare cell states, reconstruct developmental trajectories, and measure phenotype in new terms such as cellular variance. The characterization of anatomy and developmental dynamics has not had an equivalent breakthrough since groundbreaking advances in live fluorescent microscopy. The new resolution obtained by single-cell RNA-seq is a boon to genetics because the novel description of phenotype offers the opportunity to refine gene function and dissect pleiotropy. In addition, the recent pairing of high-throughput genetic perturbation with single-cell RNA-seq has made practical a scale of genetic screening not previously possible.}, } @article {pmid30192387, year = {2018}, author = {Matysioková, B and Remeš, V}, title = {Evolution of parental activity at the nest is shaped by the risk of nest predation and ambient temperature across bird species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2214-2224}, doi = {10.1111/evo.13580}, pmid = {30192387}, issn = {1558-5646}, abstract = {Incubation is an important component of parental care in birds, and species differ widely in their incubation rhythm. In this comparative study, we focused on factors responsible for those differences. As hypothesized by A. Skutch, increased parental activity at the nest increases the probability of nest depredation. High risk of nest predation should therefore lead to the evolution of lower frequency of parental activity at the nest. We thus expected to find a negative relationship between frequency of nest visits and the risk of nest depredation. Using a large dataset of 256 species of passerines breeding worldwide, we found that the frequency of nest visits decreased as the risk of nest depredation increased and that this effect was strongest in tropical species. Further, foraging bouts were longer in species experiencing warmer ambient temperatures during incubation and those with domed nests. Incubation bouts were longer and frequency of nest visits was lower in species with higher body mass. Our results support the view that natural selection favors lower frequency of nests visits in species under higher risk of nest predation and demonstrate the importance of other factors (temperature, geographic space, nest type, and body mass) in shaping the evolution of incubation rhythm.}, } @article {pmid30192223, year = {2018}, author = {Borel, N and Bavoil, P and Greub, G and Horn, M}, title = {International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of Chlamydiae. Minutes of the closed meeting, 9 April 2017, Charlotte, USA.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {3369-3370}, doi = {10.1099/ijsem.0.003010}, pmid = {30192223}, issn = {1466-5034}, } @article {pmid30192222, year = {2018}, author = {de Lajudie, PM and Young, JPW}, title = {International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of rhizobia and agrobacteria Minutes of the closed meeting, Granada, 4 September 2017.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3363-3368}, doi = {10.1099/ijsem.0.002974}, pmid = {30192222}, issn = {1466-5034}, } @article {pmid30191662, year = {2018}, author = {Dick, C and Arendt, J and Reznick, DN and Hayashi, CY}, title = {The developmental and genetic trajectory of coloration in the guppy (Poecilia reticulata).}, journal = {Evolution & development}, volume = {20}, number = {6}, pages = {207-218}, doi = {10.1111/ede.12268}, pmid = {30191662}, issn = {1525-142X}, mesh = {Animal Fins/physiology ; Animals ; Female ; Male ; *Pigmentation ; Poecilia/*genetics/*growth & development/physiology ; Sex Characteristics ; Transcriptome ; }, abstract = {Examining the association between trait variation and development is crucial for understanding the evolution of phenotypic differences. Male guppy ornamental caudal fin coloration is one trait that shows a striking degree of variation within and between guppy populations. Males initially have no caudal fin coloration, then gradually develop it as they reach sexual maturity. For males, there is a trade-off between female preference for caudal fin coloration and increased visibility to predators. This trade-off may reach unique endpoints in males from different predation regimes. Caudal fin coloration includes black melanin, orange/yellow pteridines or carotenoids, and shimmering iridescence. This study examined the phenotypic trajectory and genetics associated with color development. We found that black coloration always developed first, followed by orange/yellow, then iridescence. The ordering and timing of color appearance was the same regardless of predation regime. The increased expression of melanin synthesis genes correlated well with the visual appearance of black coloration, but there was no correlation between carotenoids or pteridine synthesis gene expression and the appearance of orange/yellow. The lack of orange/yellow coloration in earlier male caudal fin developmental stages may be due to reduced expression of genes underlying the development of orange/yellow xanthophores.}, } @article {pmid30190437, year = {2018}, author = {Rasp, S and Pritchard, MS and Gentine, P}, title = {Deep learning to represent subgrid processes in climate models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9684-9689}, pmid = {30190437}, issn = {1091-6490}, abstract = {The representation of nonlinear subgrid processes, especially clouds, has been a major source of uncertainty in climate models for decades. Cloud-resolving models better represent many of these processes and can now be run globally but only for short-term simulations of at most a few years because of computational limitations. Here we demonstrate that deep learning can be used to capture many advantages of cloud-resolving modeling at a fraction of the computational cost. We train a deep neural network to represent all atmospheric subgrid processes in a climate model by learning from a multiscale model in which convection is treated explicitly. The trained neural network then replaces the traditional subgrid parameterizations in a global general circulation model in which it freely interacts with the resolved dynamics and the surface-flux scheme. The prognostic multiyear simulations are stable and closely reproduce not only the mean climate of the cloud-resolving simulation but also key aspects of variability, including precipitation extremes and the equatorial wave spectrum. Furthermore, the neural network approximately conserves energy despite not being explicitly instructed to. Finally, we show that the neural network parameterization generalizes to new surface forcing patterns but struggles to cope with temperatures far outside its training manifold. Our results show the feasibility of using deep learning for climate model parameterization. In a broader context, we anticipate that data-driven Earth system model development could play a key role in reducing climate prediction uncertainty in the coming decade.}, } @article {pmid30190436, year = {2018}, author = {Li, H and Lu, L and Li, X and Buffet, PA and Dao, M and Karniadakis, GE and Suresh, S}, title = {Mechanics of diseased red blood cells in human spleen and consequences for hereditary blood disorders.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9574-9579}, pmid = {30190436}, issn = {1091-6490}, support = {U01 HL114476/HL/NHLBI NIH HHS/United States ; U01 HL116323/HL/NHLBI NIH HHS/United States ; }, mesh = {Ankyrins/genetics ; Cytoskeleton ; Elliptocytosis, Hereditary/blood/genetics/*pathology/surgery ; Erythrocyte Count ; Erythrocytes/*metabolism ; Hemodynamics/physiology ; Humans ; Lipid Bilayers/metabolism ; *Models, Biological ; Osmosis/*physiology ; Spectrin/genetics ; Spherocytosis, Hereditary/blood/genetics/*pathology/surgery ; Spleen/*metabolism/pathology ; Splenectomy ; Treatment Outcome ; }, abstract = {In red blood cell (RBC) diseases, the spleen contributes to anemia by clearing the damaged RBCs, but its unique ability to mechanically challenge RBCs also poses the risk of inducing other pathogenic effects. We have analyzed RBCs in hereditary spherocytosis (HS) and hereditary elliptocytosis (HE), two typical examples of blood disorders that result in membrane protein defects in RBCs. We use a two-component protein-scale RBC model to simulate the traversal of the interendothelial slit (IES) in the human spleen, a stringent biomechanical challenge on healthy and diseased RBCs that cannot be directly observed in vivo. In HS, our results confirm that the RBC loses surface due to weakened cohesion between the lipid bilayer and the cytoskeleton and reveal that surface loss may result from vesiculation of the RBC as it crosses IES. In HE, traversing IES induces sustained elongation of the RBC with impaired elasticity and fragmentation in severe disease. Our simulations thus suggest that in inherited RBC disorders, the spleen not only filters out pathological RBCs but also directly contributes to RBC alterations. These results provide a mechanistic rationale for different clinical outcomes documented following splenectomy in HS patients with spectrin-deficient and ankyrin-deficient RBCs and offer insights into the pathogenic role of human spleen in RBC diseases.}, } @article {pmid30190435, year = {2018}, author = {Kintzer, AF and Green, EM and Dominik, PK and Bridges, M and Armache, JP and Deneka, D and Kim, SS and Hubbell, W and Kossiakoff, AA and Cheng, Y and Stroud, RM}, title = {Structural basis for activation of voltage sensor domains in an ion channel TPC1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9095-E9104}, pmid = {30190435}, issn = {1091-6490}, support = {R37 GM024485/GM/NIGMS NIH HHS/United States ; S10 OD021741/OD/NIH HHS/United States ; R01 GM024485/GM/NIGMS NIH HHS/United States ; P41 GM103311/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; S10 OD020054/OD/NIH HHS/United States ; P30 EY000331/EY/NEI NIH HHS/United States ; R01 EY005216/EY/NEI NIH HHS/United States ; U54 GM087519/GM/NIGMS NIH HHS/United States ; R01 GM117372/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; R01 GM098672/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*chemistry/metabolism ; Arabidopsis Proteins/*chemistry/metabolism ; Binding Sites ; Calcium Channels/*chemistry/metabolism ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Hydrophobic and Hydrophilic Interactions ; *Ion Channel Gating ; Protein Domains ; Structure-Activity Relationship ; }, abstract = {Voltage-sensing domains (VSDs) couple changes in transmembrane electrical potential to conformational changes that regulate ion conductance through a central channel. Positively charged amino acids inside each sensor cooperatively respond to changes in voltage. Our previous structure of a TPC1 channel captured an example of a resting-state VSD in an intact ion channel. To generate an activated-state VSD in the same channel we removed the luminal inhibitory Ca2+-binding site (Cai2+), which shifts voltage-dependent opening to more negative voltage and activation at 0 mV. Cryo-EM reveals two coexisting structures of the VSD, an intermediate state 1 that partially closes access to the cytoplasmic side but remains occluded on the luminal side and an intermediate activated state 2 in which the cytoplasmic solvent access to the gating charges closes, while luminal access partially opens. Activation can be thought of as moving a hydrophobic insulating region of the VSD from the external side to an alternate grouping on the internal side. This effectively moves the gating charges from the inside potential to that of the outside. Activation also requires binding of Ca2+ to a cytoplasmic site (Caa2+). An X-ray structure with Caa2+ removed and a near-atomic resolution cryo-EM structure with Cai2+ removed define how dramatic conformational changes in the cytoplasmic domains may communicate with the VSD during activation. Together four structures provide a basis for understanding the voltage-dependent transition from resting to activated state, the tuning of VSD by thermodynamic stability, and this channel's requirement of cytoplasmic Ca2+ ions for activation.}, } @article {pmid30190434, year = {2018}, author = {Coutinho, BG and Mevers, E and Schaefer, AL and Pelletier, DA and Harwood, CS and Clardy, J and Greenberg, EP}, title = {A plant-responsive bacterial-signaling system senses an ethanolamine derivative.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9785-9790}, pmid = {30190434}, issn = {1091-6490}, support = {R01 AT009708/AT/NCCIH NIH HHS/United States ; }, mesh = {Acetamides/*metabolism/pharmacology ; Endophytes/metabolism/*physiology ; Ethanolamine/*metabolism ; Gene Expression Regulation, Bacterial ; Mass Spectrometry ; Periplasmic Binding Proteins/metabolism ; Plant Growth Regulators/metabolism/*physiology ; Plant Leaves/metabolism ; Plant Roots/microbiology ; Populus/metabolism/*microbiology ; Pseudomonas/metabolism/*physiology ; Repressor Proteins/metabolism/physiology ; Trans-Activators/metabolism/physiology ; }, abstract = {Certain plant-associated Proteobacteria sense their host environment by detecting an unknown plant signal recognized by a member of a LuxR subfamily of transcription factors. This interkingdom communication is important for both mutualistic and pathogenic interactions. The Populus root endophyte Pseudomonas sp. GM79 possesses such a regulator, named PipR. In a previous study we reported that PipR activates an adjacent gene (pipA) coding for a proline iminopeptidase in response to Populus leaf macerates and peptides and that this activation is dependent on a putative ABC-type transporter [Schaefer AL, et al. (2016) mBio 7:e01101-16]. In this study we identify a chemical derived from ethanolamine that induces PipR activity at picomolar concentrations, and we present evidence that this is the active inducer present in plant leaf macerates. First, a screen of more than 750 compounds indicated ethanolamine was a potent inducer for the PipR-sensing system; however, ethanolamine failed to bind to the periplasmic-binding protein (PBP) required for the signal response. This led us to discover that a specific ethanolamine derivative, N-(2-hydroxyethyl)-2-(2-hydroxyethylamino) acetamide (HEHEAA), binds to the PBP and serves as a potent PipR-dependent inducer. We also show that a compound, which coelutes with HEHEAA in HPLC and induces pipA gene expression in a PipR-dependent manner, can be found in Populus leaf macerates. This work sheds light on how plant-associated bacteria can sense their environment and on the nature of inducers for a family of plant-responsive LuxR-like transcription factors found in plant-associated bacteria.}, } @article {pmid30190433, year = {2018}, author = {Childs, AM and Maslov, D and Nam, Y and Ross, NJ and Su, Y}, title = {Toward the first quantum simulation with quantum speedup.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9456-9461}, pmid = {30190433}, issn = {1091-6490}, abstract = {With quantum computers of significant size now on the horizon, we should understand how to best exploit their initially limited abilities. To this end, we aim to identify a practical problem that is beyond the reach of current classical computers, but that requires the fewest resources for a quantum computer. We consider quantum simulation of spin systems, which could be applied to understand condensed matter phenomena. We synthesize explicit circuits for three leading quantum simulation algorithms, using diverse techniques to tighten error bounds and optimize circuit implementations. Quantum signal processing appears to be preferred among algorithms with rigorous performance guarantees, whereas higher-order product formulas prevail if empirical error estimates suffice. Our circuits are orders of magnitude smaller than those for the simplest classically infeasible instances of factoring and quantum chemistry, bringing practical quantum computation closer to reality.}, } @article {pmid30190432, year = {2018}, author = {Pongrakhananon, V and Saito, H and Hiver, S and Abe, T and Shioi, G and Meng, W and Takeichi, M}, title = {CAMSAP3 maintains neuronal polarity through regulation of microtubule stability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9750-9755}, pmid = {30190432}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Acetylation ; Animals ; *Cell Polarity ; Hippocampus/cytology ; Mice ; Mice, Knockout ; Microtubule-Associated Proteins/*physiology ; Microtubules/*metabolism ; Neurons/*metabolism ; Tubulin/metabolism ; }, abstract = {The molecular mechanisms that guide each neuron to become polarized, forming a single axon and multiple dendrites, remain unknown. Here we show that CAMSAP3 (calmodulin-regulated spectrin-associated protein 3), a protein that regulates the minus-end dynamics of microtubules, plays a key role in maintaining neuronal polarity. In mouse hippocampal neurons, CAMSAP3 was enriched in axons. Although axonal microtubules were generally acetylated, CAMSAP3 was preferentially localized along a less-acetylated fraction of the microtubules. CAMSAP3-mutated neurons often exhibited supernumerary axons, along with an increased number of neurites having nocodazole-resistant/acetylated microtubules compared with wild-type neurons. Analysis using cell lines showed that CAMSAP3 depletion promoted tubulin acetylation, and conversely, mild overexpression of CAMSAP3 inhibited it, suggesting that CAMSAP3 works to retain nonacetylated microtubules. In contrast, CAMSAP2, a protein related to CAMSAP3, was detected along all neurites, and its loss did not affect neuronal polarity, nor did it cause increased tubulin acetylation. Depletion of α-tubulin acetyltransferase-1 (αTAT1), the key enzyme for tubulin acetylation, abolished CAMSAP3 loss-dependent multiple-axon formation. These observations suggest that CAMSAP3 sustains a nonacetylated pool of microtubules in axons, interfering with the action of αTAT1, and this process is important to maintain neuronal polarity.}, } @article {pmid30190431, year = {2018}, author = {Parks, RJ and Gussoni, E}, title = {Building immune tolerance through DNA vaccination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9652-9654}, pmid = {30190431}, issn = {1091-6490}, mesh = {DNA ; *Immune Tolerance ; *Vaccination ; Vaccines, DNA ; }, } @article {pmid30190430, year = {2018}, author = {Xu, F and Bandara, A and Akiyama, H and Eshaghi, B and Stelter, D and Keyes, T and Straub, JE and Gummuluru, S and Reinhard, BM}, title = {Membrane-wrapped nanoparticles probe divergent roles of GM3 and phosphatidylserine in lipid-mediated viral entry pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9041-E9050}, pmid = {30190430}, issn = {1091-6490}, support = {R01 AI064099/AI/NIAID NIH HHS/United States ; R01 AI132111/AI/NIAID NIH HHS/United States ; R01 CA138509/CA/NCI NIH HHS/United States ; R01 GM107703/GM/NIGMS NIH HHS/United States ; }, mesh = {G(M3) Ganglioside/*metabolism ; *Gold ; Humans ; Lysosomes/metabolism/virology ; Macrophages/*metabolism/virology ; *Membranes, Artificial ; *Metal Nanoparticles ; Phosphatidylserines/*metabolism ; Sialic Acid Binding Ig-like Lectin 1/metabolism ; THP-1 Cells ; Tetraspanin 29/metabolism ; *Virus Internalization ; Viruses/*metabolism ; }, abstract = {Gold nanoparticles (NPs) wrapped in a membrane can be utilized as artificial virus nanoparticles (AVNs) that combine the large nonblinking or bleaching optical cross-section of the NP core with the biological surface properties and functionalities provided by a self-assembled lipid membrane. We used these hybrid nanomaterials to test the roles of monosialodihexosylganglioside (GM3) and phosphatidylserine (PS) for a lipid-mediated targeting of virus-containing compartments (VCCs) in macrophages. GM3-presenting AVNs bind to CD169 (Siglec-1)-expressing macrophages, but inclusion of PS in the GM3-containing AVN membrane decreases binding. Molecular dynamics simulations of the AVN membrane and experimental binding studies of CD169 to GM3-presenting AVNs reveal Na+-mediated interactions between GM3 and PS as a potential cause of the antagonistic action on binding by the two negatively charged lipids. GM3-functionalized AVNs with no or low PS content localize to tetherin+, CD9+ VCC in a membrane composition-depending fashion, but increasing amounts of PS in the AVN membrane redirect the NP to lysosomal compartments. Interestingly, this compartmentalization is highly GM3 specific. Even AVNs presenting the related monosialotetrahexosylganglioside (GM1) fail to achieve an accumulation in VCC. AVN localization to VCC was observed for AVN with gold NP core but not for liposomes, suggesting that NP sequestration into VCC has additional requirements beyond ligand (GM3)-receptor (CD169) recognition that are related to the physical properties of the NP core. Our results confirm AVN as a scalable platform for elucidating the mechanisms of lipid-mediated viral entry pathways and for selective intracellular targeting.}, } @article {pmid30190429, year = {2018}, author = {Papageorgiou, DP and Abidi, SZ and Chang, HY and Li, X and Kato, GJ and Karniadakis, GE and Suresh, S and Dao, M}, title = {Simultaneous polymerization and adhesion under hypoxia in sickle cell disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9473-9478}, pmid = {30190429}, issn = {1091-6490}, support = {R01 HL121386/HL/NHLBI NIH HHS/United States ; U01 HL114476/HL/NHLBI NIH HHS/United States ; }, mesh = {Anemia, Sickle Cell/*blood/pathology ; Cell Adhesion ; Cell Hypoxia ; Erythrocytes/*metabolism ; Erythrocytes, Abnormal/*metabolism ; Hemoglobin, Sickle/*metabolism ; Humans ; Hypoxia ; Microfluidics/methods ; Polymerization ; Reticulocytes/metabolism ; }, abstract = {Polymerization and adhesion, dynamic processes that are hallmarks of sickle cell disease (SCD), have thus far been studied in vitro only separately. Here, we present quantitative results of the simultaneous and synergistic effects of adhesion and polymerization of deoxygenated sickle hemoglobin (HbS) in the human red blood cell (RBC) on the mechanisms underlying vasoocclusive pain crisis. For this purpose, we employ a specially developed hypoxic microfluidic platform, which is capable of inducing sickling and unsickling of RBCs in vitro, to test blood samples from eight patients with SCD. We supplemented these experimental results with detailed molecular-level computational simulations of cytoadherence and biorheology using dissipative particle dynamics. By recourse to image analysis techniques, we characterize sickle RBC maturation stages in the following order of the degree of adhesion susceptibility under hypoxia: sickle reticulocytes in circulation (SRs) → sickle mature erythrocytes (SMEs) → irreversibly sickled cells (ISCs). We show that (i) hypoxia significantly enhances sickle RBC adherence; (ii) HbS polymerization enhances sickle cell adherence in SRs and SMEs, but not in ISCs; (iii) SRs exhibit unique adhesion dynamics where HbS fiber projections growing outward from the cell surface create multiple sites of adhesion; and (iv) polymerization stimulates adhesion and vice versa, thereby establishing the bidirectional coupling between the two processes. These findings offer insights into possible mechanistic pathways leading to vasoocclusion crisis. They also elucidate the processes underlying the onset of occlusion that may involve circulating reticulocytes, which are more abundant in hemolytic anemias due to robust compensatory erythropoiesis.}, } @article {pmid30190428, year = {2018}, author = {Mizrahi, V and Warner, DF}, title = {Death of Mycobacterium tuberculosis by l-arginine starvation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9658-9660}, pmid = {30190428}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Arginine ; Humans ; *Mycobacterium tuberculosis ; Starvation ; Tuberculosis ; }, } @article {pmid30190427, year = {2018}, author = {Chu, B and He, A and Tian, Y and He, W and Chen, P and Hu, J and Xu, R and Zhou, W and Zhang, M and Yang, P and Li, SSC and Sun, Y and Li, P and Hunter, T and Tian, R}, title = {Photoaffinity-engineered protein scaffold for systematically exploring native phosphotyrosine signaling complexes in tumor samples.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8863-E8872}, pmid = {30190427}, issn = {1091-6490}, mesh = {Animals ; Benzimidazoles/pharmacology ; Biomarkers, Tumor/*metabolism ; Breast Neoplasms/diagnosis/genetics/*pathology ; Cancer-Associated Fibroblasts/pathology ; Cell Line, Tumor ; Female ; Humans ; Mammary Tumor Virus, Mouse/genetics ; Mass Spectrometry ; Mice, Transgenic ; Phosphorylation ; Phosphotyrosine/*metabolism ; Piperidines/pharmacology ; Protein Binding ; Protein Engineering/*methods ; Proteomics/*methods ; Receptor, ErbB-2/metabolism ; Receptor, Platelet-Derived Growth Factor beta/metabolism ; Signal Transduction/drug effects ; Ultraviolet Rays ; src Homology Domains/genetics/radiation effects ; }, abstract = {Phosphotyrosine (pTyr)-regulated protein complexes play critical roles in cancer signaling. The systematic characterization of these protein complexes in tumor samples remains a challenge due to their limited access and the transient nature of pTyr-mediated interactions. We developed a hybrid chemical proteomics approach, termed Photo-pTyr-scaffold, by engineering Src homology 2 (SH2) domains, which specifically bind pTyr proteins, with both trifunctional chemical probes and genetic mutations to overcome these challenges. Dynamic SH2 domain-scaffolding protein complexes were efficiently cross-linked under mild UV light, captured by biotin tag, and identified by mass spectrometry. This approach was successfully used to profile native pTyr protein complexes from breast cancer tissue samples on a proteome scale with high selectivity, achieving about 100 times higher sensitivity for detecting pTyr signaling proteins than that afforded by traditional immunohistochemical methods. Among more than 1,000 identified pTyr proteins, receptor tyrosine kinase PDGFRB expressed on cancer-associated fibroblasts was validated as an important intercellular signaling regulator with poor expression correlation to ERBB2, and blockade of PDGFRB signaling could efficiently suppress tumor growth. The Photo-pTyr-scaffold approach may become a generic tool for readily profiling dynamic pTyr signaling complexes in clinically relevant samples.}, } @article {pmid30190426, year = {2018}, author = {Sperandio, V}, title = {Pathogens' adaptation to the human host.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9342-9343}, pmid = {30190426}, issn = {1091-6490}, support = {R37 AI053067/AI/NIAID NIH HHS/United States ; }, mesh = {Acclimatization ; *Adaptation, Physiological ; *Host-Pathogen Interactions ; Humans ; }, } @article {pmid30190425, year = {2018}, author = {Shimizu, H and Toma-Fukai, S and Kontani, K and Katada, T and Shimizu, T}, title = {GEF mechanism revealed by the structure of SmgGDS-558 and farnesylated RhoA complex and its implication for a chaperone mechanism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9563-9568}, pmid = {30190425}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Drug Design ; Enzyme Assays ; Guanine Nucleotide Exchange Factors/antagonists & inhibitors/*chemistry/metabolism ; Humans ; Molecular Chaperones/*chemistry/metabolism ; Molecular Docking Simulation ; Monomeric GTP-Binding Proteins/*metabolism ; Prenylation/physiology ; Protein Binding ; *Protein Folding ; rhoA GTP-Binding Protein/*chemistry/metabolism ; }, abstract = {SmgGDS has dual functions in cells and regulates small GTPases as both a guanine nucleotide exchange factor (GEF) for the Rho family and a molecular chaperone for small GTPases possessing a C-terminal polybasic region followed by four C-terminal residues called the CaaX motif, which is posttranslationally prenylated at its cysteine residue. Our recent structural work revealed that SmgGDS folds into tandem copies of armadillo-repeat motifs (ARMs) that are not present in other GEFs. However, the precise mechanism of GEF activity and recognition mechanism for the prenylated CaaX motif remain unknown because SmgGDS does not have a typical GEF catalytic domain and lacks a pocket to accommodate a prenyl group. Here, we aimed to determine the crystal structure of the SmgGDS/farnesylated RhoA complex. We found that SmgGDS induces a significant conformational change in the switch I and II regions that opens up the nucleotide-binding site, with the prenyl group fitting into the cryptic pocket in the N-terminal ARMs. Taken together, our findings could advance the understanding of the role of SmgGDS and enable drug design strategies for targeting SmgGDS and small GTPases.}, } @article {pmid30190409, year = {2018}, author = {Anderson, S}, title = {Outsmarting our instruments.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1042}, doi = {10.1126/science.361.6406.1042}, pmid = {30190409}, issn = {1095-9203}, } @article {pmid30190408, year = {2018}, author = {Reiter, JG and Makohon-Moore, AP and Gerold, JM and Heyde, A and Attiyeh, MA and Kohutek, ZA and Tokheim, CJ and Brown, A and DeBlasio, RM and Niyazov, J and Zucker, A and Karchin, R and Kinzler, KW and Iacobuzio-Donahue, CA and Vogelstein, B and Nowak, MA}, title = {Minimal functional driver gene heterogeneity among untreated metastases.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1033-1037}, doi = {10.1126/science.aat7171}, pmid = {30190408}, issn = {1095-9203}, support = {T32 CA160001/CA/NCI NIH HHS/United States ; R37 CA043460/CA/NCI NIH HHS/United States ; F31 CA180682/CA/NCI NIH HHS/United States ; R01 CA179991/CA/NCI NIH HHS/United States ; F31 CA200266/CA/NCI NIH HHS/United States ; K99 CA229991/CA/NCI NIH HHS/United States ; U24 CA204817/CA/NCI NIH HHS/United States ; }, mesh = {*Genetic Heterogeneity ; Humans ; Models, Theoretical ; Mutation ; Neoplasm Metastasis/*drug therapy/*genetics/pathology ; Neoplasms/*drug therapy/*genetics/pathology ; }, abstract = {Metastases are responsible for the majority of cancer-related deaths. Although genomic heterogeneity within primary tumors is associated with relapse, heterogeneity among treatment-naïve metastases has not been comprehensively assessed. We analyzed sequencing data for 76 untreated metastases from 20 patients and inferred cancer phylogenies for breast, colorectal, endometrial, gastric, lung, melanoma, pancreatic, and prostate cancers. We found that within individual patients, a large majority of driver gene mutations are common to all metastases. Further analysis revealed that the driver gene mutations that were not shared by all metastases are unlikely to have functional consequences. A mathematical model of tumor evolution and metastasis formation provides an explanation for the observed driver gene homogeneity. Thus, single biopsies capture most of the functionally important mutations in metastases and therefore provide essential information for therapeutic decision-making.}, } @article {pmid30190407, year = {2018}, author = {Herberg, S and Gert, KR and Schleiffer, A and Pauli, A}, title = {The Ly6/uPAR protein Bouncer is necessary and sufficient for species-specific fertilization.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1029-1033}, pmid = {30190407}, issn = {1095-9203}, mesh = {Amino Acid Sequence ; Animals ; Female ; Male ; Mutation ; Oocytes/metabolism ; Oryzias/genetics/physiology ; Species Specificity ; *Sperm-Ovum Interactions ; Testis/metabolism ; Zebrafish/genetics/*physiology ; Zebrafish Proteins/genetics/*physiology ; }, abstract = {Fertilization is fundamental for sexual reproduction, yet its molecular mechanisms are poorly understood. We found that an oocyte-expressed Ly6/uPAR protein, which we call Bouncer, is a crucial fertilization factor in zebrafish. Membrane-bound Bouncer mediates sperm-egg binding and is thus essential for sperm entry into the egg. Remarkably, Bouncer not only is required for sperm-egg interaction but is also sufficient to allow cross-species fertilization between zebrafish and medaka, two fish species that diverged more than 200 million years ago. Our study thus identifies Bouncer as a key determinant of species-specific fertilization in fish. Bouncer's closest homolog in tetrapods, SPACA4, is restricted to the male germline in internally fertilizing vertebrates, which suggests that our findings in fish have relevance to human biology.}, } @article {pmid30190406, year = {2018}, author = {Wang, J and Zhou, L and Shi, H and Chern, M and Yu, H and Yi, H and He, M and Yin, J and Zhu, X and Li, Y and Li, W and Liu, J and Wang, J and Chen, X and Qing, H and Wang, Y and Liu, G and Wang, W and Li, P and Wu, X and Zhu, L and Zhou, JM and Ronald, PC and Li, S and Li, J and Chen, X}, title = {A single transcription factor promotes both yield and immunity in rice.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1026-1028}, doi = {10.1126/science.aat7675}, pmid = {30190406}, issn = {1095-9203}, mesh = {Gene Expression Regulation, Plant ; Magnaporthe/*immunology ; Oryza/*genetics/growth & development/*immunology ; Phosphorylation ; Plant Diseases/*immunology/*microbiology ; Plant Immunity/*genetics ; Plant Proteins/genetics/*metabolism ; Promoter Regions, Genetic ; Protein Binding ; Transcription Factors/genetics/*metabolism ; }, abstract = {Plant immunity often penalizes growth and yield. The transcription factor Ideal Plant Architecture 1 (IPA1) reduces unproductive tillers and increases grains per panicle, which results in improved rice yield. Here we report that higher IPA1 levels enhance immunity. Mechanistically, phosphorylation of IPA1 at amino acid Ser163 within its DNA binding domain occurs in response to infection by the fungus Magnaporthe oryzae and alters the DNA binding specificity of IPA1. Phosphorylated IPA1 binds to the promoter of the pathogen defense gene WRKY45 and activates its expression, leading to enhanced disease resistance. IPA1 returns to a nonphosphorylated state within 48 hours after infection, resuming support of the growth needed for high yield. Thus, IPA1 promotes both yield and disease resistance by sustaining a balance between growth and immunity.}, } @article {pmid30190405, year = {2018}, author = {Jesmer, BR and Merkle, JA and Goheen, JR and Aikens, EO and Beck, JL and Courtemanch, AB and Hurley, MA and McWhirter, DE and Miyasaki, HM and Monteith, KL and Kauffman, MJ}, title = {Is ungulate migration culturally transmitted? Evidence of social learning from translocated animals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1023-1025}, doi = {10.1126/science.aat0985}, pmid = {30190405}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; Cultural Characteristics ; Ruminants/*psychology ; Sheep, Bighorn/*psychology ; *Social Learning ; }, abstract = {Ungulate migrations are assumed to stem from learning and cultural transmission of information regarding seasonal distribution of forage, but this hypothesis has not been tested empirically. We compared the migratory propensities of bighorn sheep and moose translocated into novel habitats with those of historical populations that had persisted for hundreds of years. Whereas individuals from historical populations were largely migratory, translocated individuals initially were not. After multiple decades, however, translocated populations gained knowledge about surfing green waves of forage (tracking plant phenology) and increased their propensity to migrate. Our findings indicate that learning and cultural transmission are the primary mechanisms by which ungulate migrations evolve. Loss of migration will therefore expunge generations of knowledge about the locations of high-quality forage and likely suppress population abundance.}, } @article {pmid30190404, year = {2018}, author = {Li, Y and Kalnay, E and Motesharrei, S and Rivas, J and Kucharski, F and Kirk-Davidoff, D and Bach, E and Zeng, N}, title = {Climate model shows large-scale wind and solar farms in the Sahara increase rain and vegetation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1019-1022}, doi = {10.1126/science.aar5629}, pmid = {30190404}, issn = {1095-9203}, mesh = {Africa, Northern ; Climate ; *Climate Change ; *Farms ; Models, Theoretical ; *Plants ; *Rain ; Sunlight ; *Wind ; }, abstract = {Wind and solar farms offer a major pathway to clean, renewable energies. However, these farms would significantly change land surface properties, and, if sufficiently large, the farms may lead to unintended climate consequences. In this study, we used a climate model with dynamic vegetation to show that large-scale installations of wind and solar farms covering the Sahara lead to a local temperature increase and more than a twofold precipitation increase, especially in the Sahel, through increased surface friction and reduced albedo. The resulting increase in vegetation further enhances precipitation, creating a positive albedo-precipitation-vegetation feedback that contributes ~80% of the precipitation increase for wind farms. This local enhancement is scale dependent and is particular to the Sahara, with small impacts in other deserts.}, } @article {pmid30190403, year = {2018}, author = {Spilker, JS and Aravena, M and Béthermin, M and Chapman, SC and Chen, CC and Cunningham, DJM and De Breuck, C and Dong, C and Gonzalez, AH and Hayward, CC and Hezaveh, YD and Litke, KC and Ma, J and Malkan, M and Marrone, DP and Miller, TB and Morningstar, WR and Narayanan, D and Phadke, KA and Sreevani, J and Stark, AA and Vieira, JD and Weiß, A}, title = {Fast molecular outflow from a dusty star-forming galaxy in the early Universe.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1016-1019}, doi = {10.1126/science.aap8900}, pmid = {30190403}, issn = {1095-9203}, abstract = {Galaxies grow inefficiently, with only a small percentage of the available gas converted into stars each free-fall time. Feedback processes, such as outflowing winds driven by radiation pressure, supernovae, or supermassive black hole accretion, can act to halt star formation if they heat or expel the gas supply. We report a molecular outflow launched from a dust-rich star-forming galaxy at redshift 5.3, 1 billion years after the Big Bang. The outflow reaches velocities up to 800 kilometers per second relative to the galaxy, is resolved into multiple clumps, and carries mass at a rate within a factor of 2 of the star formation rate. Our results show that molecular outflows can remove a large fraction of the gas available for star formation from galaxies at high redshift.}, } @article {pmid30190402, year = {2018}, author = {Rusimova, KR and Purkiss, RM and Howes, R and Lee, F and Crampin, S and Sloan, PA}, title = {Regulating the femtosecond excited-state lifetime of a single molecule.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1012-1016}, doi = {10.1126/science.aat9688}, pmid = {30190402}, issn = {1095-9203}, abstract = {The key to controlling reactions of molecules induced with the current of a scanning tunneling microscope (STM) tip is the ultrashort intermediate excited ionic state. The initial condition of the excited state is set by the energy and position of the injected current; thereafter, its dynamics determines the reaction outcome. We show that a STM can directly and controllably influence the excited-state dynamics. For the STM-induced desorption of toluene molecules from the Si(111)-7x7 surface, as the tip approaches the molecule, the probability of manipulation drops by two orders of magnitude. A two-channel quenching of the excited state is proposed, consisting of an invariant surface channel and a tip height-dependent channel. We conclude that picometer tip proximity regulates the lifetime of the excited state from 10 femtoseconds to less than 0.1 femtoseconds.}, } @article {pmid30190401, year = {2018}, author = {Ma, X and Kumar, P and Mittal, N and Khlyustova, A and Daoutidis, P and Mkhoyan, KA and Tsapatsis, M}, title = {Zeolitic imidazolate framework membranes made by ligand-induced permselectivation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1008-1011}, doi = {10.1126/science.aat4123}, pmid = {30190401}, issn = {1095-9203}, abstract = {Zeolitic imidazolate framework (ZIF) membranes are emerging as a promising energy-efficient separation technology. However, their reliable and scalable manufacturing remains a challenge. We demonstrate the fabrication of ZIF nanocomposite membranes by means of an all-vapor-phase processing method based on atomic layer deposition (ALD) of ZnO in a porous support followed by ligand-vapor treatment. After ALD, the obtained nanocomposite exhibits low flux and is not selective, whereas after ligand-vapor (2-methylimidazole) treatment, it is partially transformed to ZIF and shows stable performance with high mixture separation factor for propylene over propane (an energy-intensive high-volume separation) and high propylene flux. Membrane synthesis through ligand-induced permselectivation of a nonselective and impermeable deposit is shown to be simple and highly reproducible and holds promise for scalability.}, } @article {pmid30190400, year = {2018}, author = {Kitamura, N and Kitahara, M and Shoji, M and Miyoshi, Y and Hasegawa, H and Nakamura, S and Katoh, Y and Saito, Y and Yokota, S and Gershman, DJ and Vinas, AF and Giles, BL and Moore, TE and Paterson, WR and Pollock, CJ and Russell, CT and Strangeway, RJ and Fuselier, SA and Burch, JL}, title = {Direct measurements of two-way wave-particle energy transfer in a collisionless space plasma.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1000-1003}, doi = {10.1126/science.aap8730}, pmid = {30190400}, issn = {1095-9203}, abstract = {Particle acceleration by plasma waves and spontaneous wave generation are fundamental energy and momentum exchange processes in collisionless plasmas. Such wave-particle interactions occur ubiquitously in space. We present ultrafast measurements in Earth's magnetosphere by the Magnetospheric Multiscale spacecraft that enabled quantitative evaluation of energy transfer in interactions associated with electromagnetic ion cyclotron waves. The observed ion distributions are not symmetric around the magnetic field direction but are in phase with the plasma wave fields. The wave-ion phase relations demonstrate that a cyclotron resonance transferred energy from hot protons to waves, which in turn nonresonantly accelerated cold He+ to energies up to ~2 kilo-electron volts. These observations provide direct quantitative evidence for collisionless energy transfer in plasmas between distinct particle populations via wave-particle interactions.}, } @article {pmid30190399, year = {2018}, author = {Johansson, KO and Head-Gordon, MP and Schrader, PE and Wilson, KR and Michelsen, HA}, title = {Resonance-stabilized hydrocarbon-radical chain reactions may explain soot inception and growth.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {997-1000}, doi = {10.1126/science.aat3417}, pmid = {30190399}, issn = {1095-9203}, abstract = {Mystery surrounds the transition from gas-phase hydrocarbon precursors to terrestrial soot and interstellar dust, which are carbonaceous particles formed under similar conditions. Although polycyclic aromatic hydrocarbons (PAHs) are known precursors to high-temperature carbonaceous-particle formation, the molecular pathways that initiate particle formation are unknown. We present experimental and theoretical evidence for rapid molecular clustering-reaction pathways involving radicals with extended conjugation. These radicals react with other hydrocarbon species to form covalently bound complexes that promote further growth and clustering by regenerating resonance-stabilized radicals through low-barrier hydrogen-abstraction and hydrogen-ejection reactions. Such radical-chain reaction pathways may lead to covalently bound clusters of PAHs and other hydrocarbons that would otherwise be too small to condense at high temperatures, thus providing the key mechanistic steps for rapid particle formation and surface growth by hydrocarbon chemisorption.}, } @article {pmid30190398, year = {2018}, author = {Hulbert, JM and Roets, F}, title = {Science engagement in South Africa.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {985}, doi = {10.1126/science.aav1499}, pmid = {30190398}, issn = {1095-9203}, mesh = {*Plant Diseases ; Research/*education ; South Africa ; Students ; }, } @article {pmid30190397, year = {2018}, author = {Anbar, A and Elgin, S and Jez, J and O'Dowd, D and Shapiro, B and Zaman, M}, title = {Improving societies' harassment policies.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {984-985}, doi = {10.1126/science.aav1362}, pmid = {30190397}, issn = {1095-9203}, } @article {pmid30190396, year = {2018}, author = {Selin, NE and Kenney, MA and Jefferson, AJ and Dukes, JS and Hill, TM and Olabisi, LS and Duffy, MA}, title = {Call for new AAAS harassment policy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {984}, doi = {10.1126/science.aav1680}, pmid = {30190396}, issn = {1095-9203}, } @article {pmid30190395, year = {2018}, author = {Glaser, A and Mian, Z}, title = {Denuclearizing North Korea: A verified, phased approach.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {981-983}, doi = {10.1126/science.aau4817}, pmid = {30190395}, issn = {1095-9203}, } @article {pmid30190394, year = {2018}, author = {Portegies Zwart, S}, title = {Computational astrophysics for the future.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {979-980}, doi = {10.1126/science.aau3206}, pmid = {30190394}, issn = {1095-9203}, } @article {pmid30190393, year = {2018}, author = {Thomson, M and Mitra, T}, title = {A radical approach to soot formation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {978-979}, doi = {10.1126/science.aau5941}, pmid = {30190393}, issn = {1095-9203}, mesh = {Hydrocarbons/chemistry ; *Soot ; }, } @article {pmid30190392, year = {2018}, author = {Greene, GH and Dong, X}, title = {To grow and to defend.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {976-977}, doi = {10.1126/science.aau9065}, pmid = {30190392}, issn = {1095-9203}, mesh = {Immunity ; Oryza/*growth & development ; *Transcription Factors ; }, } @article {pmid30190391, year = {2018}, author = {Spires-Jones, TL and Ritchie, CW}, title = {A brain boost to fight Alzheimer's disease.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {975-976}, doi = {10.1126/science.aau8060}, pmid = {30190391}, issn = {1095-9203}, mesh = {*Alzheimer Disease ; *Brain ; Humans ; }, } @article {pmid30190390, year = {2018}, author = {Lehmann, R}, title = {Matchmaking molecule for egg and sperm.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {974-975}, doi = {10.1126/science.aau8356}, pmid = {30190390}, issn = {1095-9203}, } @article {pmid30190389, year = {2018}, author = {Festa-Bianchet, M}, title = {Learning to migrate.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {972-973}, doi = {10.1126/science.aau6835}, pmid = {30190389}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; *Learning ; *Social Behavior ; }, } @article {pmid30190388, year = {2018}, author = {Cornwall, W}, title = {How triage became a dirty word.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {965}, doi = {10.1126/science.361.6406.965}, pmid = {30190388}, issn = {1095-9203}, mesh = {Animals ; Cost-Benefit Analysis ; Endangered Species/*economics/*legislation & jurisprudence ; Federal Government ; *Investments ; United States ; }, } @article {pmid30190387, year = {2018}, author = {Cornwall, W}, title = {Should it be saved?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {962-965}, doi = {10.1126/science.361.6406.962}, pmid = {30190387}, issn = {1095-9203}, mesh = {Animals ; British Columbia ; Endangered Species/*economics ; *Extinction, Biological ; Human Activities ; Humans ; *Reindeer ; Trout ; }, } @article {pmid30190386, year = {2018}, author = {Stone, R}, title = {Renewed sanctions strangle science in Iran.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {961}, doi = {10.1126/science.361.6406.961}, pmid = {30190386}, issn = {1095-9203}, } @article {pmid30190385, year = {2018}, author = {Escobar, H}, title = {In a 'foretold tragedy,' fire consumes Brazil museum.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {960}, doi = {10.1126/science.361.6406.960}, pmid = {30190385}, issn = {1095-9203}, } @article {pmid30190384, year = {2018}, author = {Wadman, M}, title = {'Rapid onset' of transgender identity ignites storm.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {958-959}, doi = {10.1126/science.361.6406.958}, pmid = {30190384}, issn = {1095-9203}, mesh = {Adolescent ; Bias ; Female ; Gender Dysphoria/epidemiology/*psychology ; *Gender Identity ; Humans ; Male ; Psychology ; Self-Assessment ; Transgender Persons/*psychology ; Young Adult ; }, } @article {pmid30190383, year = {2018}, author = {Enserink, M}, title = {European funders seek to end reign of paywalled journals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {957-958}, doi = {10.1126/science.361.6406.957}, pmid = {30190383}, issn = {1095-9203}, } @article {pmid30190382, year = {2018}, author = {Kintisch, E}, title = {U.N. tackles gene prospecting on the high seas.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {956-957}, doi = {10.1126/science.361.6406.956}, pmid = {30190382}, issn = {1095-9203}, mesh = {Animals ; Aquatic Organisms/*genetics ; *Biodiversity ; *Genes ; Oceans and Seas ; Patents as Topic/*legislation & jurisprudence ; Scyphozoa/genetics ; Sequence Analysis, DNA ; United Nations ; }, } @article {pmid30190381, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {954-955}, doi = {10.1126/science.361.6406.954}, pmid = {30190381}, issn = {1095-9203}, } @article {pmid30190380, year = {2018}, author = {Alisic, E and Hilgenkamp, H}, title = {New voices, at last.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {953}, doi = {10.1126/science.aav2338}, pmid = {30190380}, issn = {1095-9203}, } @article {pmid30190379, year = {2018}, author = {Choi, SH and Bylykbashi, E and Chatila, ZK and Lee, SW and Pulli, B and Clemenson, GD and Kim, E and Rompala, A and Oram, MK and Asselin, C and Aronson, J and Zhang, C and Miller, SJ and Lesinski, A and Chen, JW and Kim, DY and van Praag, H and Spiegelman, BM and Gage, FH and Tanzi, RE}, title = {Combined adult neurogenesis and BDNF mimic exercise effects on cognition in an Alzheimer's mouse model.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {}, pmid = {30190379}, issn = {1095-9203}, support = {R01 AG014713/AG/NIA NIH HHS/United States ; RF1 AG048080/AG/NIA NIH HHS/United States ; R01 MH060009/MH/NIMH NIH HHS/United States ; }, mesh = {Alzheimer Disease/pathology/*psychology/*therapy ; Amyloid beta-Peptides ; Amyloid beta-Protein Precursor/genetics/metabolism ; Animals ; Brain-Derived Neurotrophic Factor/*metabolism ; Carbazoles/administration & dosage/pharmacology ; Cell Death ; *Cognition ; Disease Models, Animal ; *Exercise ; Female ; Fibronectins ; Hippocampus/*cytology ; Humans ; Interleukin-6/metabolism ; Male ; Mice ; Mice, Transgenic ; *Neurogenesis/drug effects ; Physical Conditioning, Animal ; Wnt3 Protein/genetics ; }, abstract = {Adult hippocampal neurogenesis (AHN) is impaired before the onset of Alzheimer's disease (AD) pathology. We found that exercise provided cognitive benefit to 5×FAD mice, a mouse model of AD, by inducing AHN and elevating levels of brain-derived neurotrophic factor (BDNF). Neither stimulation of AHN alone, nor exercise, in the absence of increased AHN, ameliorated cognition. We successfully mimicked the beneficial effects of exercise on AD mice by genetically and pharmacologically inducing AHN in combination with elevating BDNF levels. Suppressing AHN later led to worsened cognitive performance and loss of preexisting dentate neurons. Thus, pharmacological mimetics of exercise, enhancing AHN and elevating BDNF levels, may improve cognition in AD. Furthermore, applied at early stages of AD, these mimetics may protect against subsequent neuronal cell death.}, } @article {pmid30190378, year = {2018}, author = {Hastings, A and Abbott, KC and Cuddington, K and Francis, T and Gellner, G and Lai, YC and Morozov, A and Petrovskii, S and Scranton, K and Zeeman, ML}, title = {Transient phenomena in ecology.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {}, doi = {10.1126/science.aat6412}, pmid = {30190378}, issn = {1095-9203}, mesh = {Animals ; Classification ; *Ecosystem ; Human Activities ; Humans ; Models, Theoretical ; }, abstract = {The importance of transient dynamics in ecological systems and in the models that describe them has become increasingly recognized. However, previous work has typically treated each instance of these dynamics separately. We review both empirical examples and model systems, and outline a classification of transient dynamics based on ideas and concepts from dynamical systems theory. This classification provides ways to understand the likelihood of transients for particular systems, and to guide investigations to determine the timing of sudden switches in dynamics and other characteristics of transients. Implications for both management and underlying ecological theories emerge.}, } @article {pmid30190377, year = {2018}, author = {}, title = {Erratum for the Report "Degradation of microRNAs by a Family of Exoribonucleases in Arabidopsis" by V. Ramachandran, X. Chen.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {}, doi = {10.1126/science.aav2481}, pmid = {30190377}, issn = {1095-9203}, } @article {pmid30190311, year = {2018}, author = {Nakatsuka, N and Yang, KA and Abendroth, JM and Cheung, KM and Xu, X and Yang, H and Zhao, C and Zhu, B and Rim, YS and Yang, Y and Weiss, PS and Stojanović, MN and Andrews, AM}, title = {Aptamer-field-effect transistors overcome Debye length limitations for small-molecule sensing.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {319-324}, doi = {10.1126/science.aao6750}, pmid = {30190311}, issn = {1095-9203}, support = {R01 DA045550/DA/NIDA NIH HHS/United States ; R21 CA199849/CA/NCI NIH HHS/United States ; R01 GM104960/GM/NIGMS NIH HHS/United States ; }, mesh = {Aptamers, Nucleotide/*chemistry ; *Biosensing Techniques ; Dopamine/analysis ; Glucose/analysis ; Lysophospholipids/analysis ; Serotonin/analysis ; Sphingosine/analogs & derivatives/analysis ; Transistors, Electronic ; }, abstract = {Detection of analytes by means of field-effect transistors bearing ligand-specific receptors is fundamentally limited by the shielding created by the electrical double layer (the "Debye length" limitation). We detected small molecules under physiological high-ionic strength conditions by modifying printed ultrathin metal-oxide field-effect transistor arrays with deoxyribonucleotide aptamers selected to bind their targets adaptively. Target-induced conformational changes of negatively charged aptamer phosphodiester backbones in close proximity to semiconductor channels gated conductance in physiological buffers, resulting in highly sensitive detection. Sensing of charged and electroneutral targets (serotonin, dopamine, glucose, and sphingosine-1-phosphate) was enabled by specifically isolated aptameric stem-loop receptors.}, } @article {pmid30190310, year = {2018}, author = {Mena, EL and Kjolby, RAS and Saxton, RA and Werner, A and Lew, BG and Boyle, JM and Harland, R and Rape, M}, title = {Dimerization quality control ensures neuronal development and survival.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {}, doi = {10.1126/science.aap8236}, pmid = {30190310}, issn = {1095-9203}, support = {R01 GM042341/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *BTB-POZ Domain ; Cell Survival ; F-Box Proteins/genetics/*metabolism ; Humans ; Mutation ; Neural Crest/cytology/embryology ; *Neurogenesis ; Neurons/*physiology ; *Protein Multimerization ; Ubiquitin-Protein Ligases/*metabolism ; Xenopus laevis ; }, abstract = {Aberrant complex formation by recurrent interaction modules, such as BTB domains, leucine zippers, or coiled coils, can disrupt signal transduction, yet whether cells detect and eliminate complexes of irregular composition is unknown. By searching for regulators of the BTB family, we discovered a quality control pathway that ensures functional dimerization [dimerization quality control (DQC)]. Key to this network is the E3 ligase SCFFBXL17, which selectively binds and ubiquitylates BTB dimers of aberrant composition to trigger their clearance by proteasomal degradation. Underscoring the physiological importance of DQC, SCFFBXL17 is required for the differentiation, function, and survival of neural crest and neuronal cells. We conclude that metazoan organisms actively monitor BTB dimerization, and we predict that distinct E3 ligases similarly control complex formation by other recurrent domains.}, } @article {pmid30190309, year = {2018}, author = {Pan, X and Li, Z and Zhou, Q and Shen, H and Wu, K and Huang, X and Chen, J and Zhang, J and Zhu, X and Lei, J and Xiong, W and Gong, H and Xiao, B and Yan, N}, title = {Structure of the human voltage-gated sodium channel Nav1.4 in complex with β1.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {}, doi = {10.1126/science.aau2486}, pmid = {30190309}, issn = {1095-9203}, mesh = {Allosteric Regulation ; Amino Acid Sequence ; Channelopathies/genetics/metabolism ; Cryoelectron Microscopy ; Drug Discovery ; HEK293 Cells ; Humans ; Mutation ; NAV1.4 Voltage-Gated Sodium Channel/*chemistry/genetics/ultrastructure ; Protein Domains ; Voltage-Gated Sodium Channel beta-4 Subunit/*chemistry/genetics/ultrastructure ; }, abstract = {Voltage-gated sodium (Nav) channels, which are responsible for action potential generation, are implicated in many human diseases. Despite decades of rigorous characterization, the lack of a structure of any human Nav channel has hampered mechanistic understanding. Here, we report the cryo-electron microscopy structure of the human Nav1.4-β1 complex at 3.2-Å resolution. Accurate model building was made for the pore domain, the voltage-sensing domains, and the β1 subunit, providing insight into the molecular basis for Na+ permeation and kinetic asymmetry of the four repeats. Structural analysis of reported functional residues and disease mutations corroborates an allosteric blocking mechanism for fast inactivation of Nav channels. The structure provides a path toward mechanistic investigation of Nav channels and drug discovery for Nav channelopathies.}, } @article {pmid30190308, year = {2018}, author = {Marino, ND and Zhang, JY and Borges, AL and Sousa, AA and Leon, LM and Rauch, BJ and Walton, RT and Berry, JD and Joung, JK and Kleinstiver, BP and Bondy-Denomy, J}, title = {Discovery of widespread type I and type V CRISPR-Cas inhibitors.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {240-242}, doi = {10.1126/science.aau5174}, pmid = {30190308}, issn = {1095-9203}, support = {DP5 OD021344/OD/NIH HHS/United States ; R01 GM127489/GM/NIGMS NIH HHS/United States ; K99 CA218870/CA/NCI NIH HHS/United States ; R35 GM118158/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; *CRISPR-Cas Systems ; Cell Line ; Computational Biology/methods ; Endonucleases/*antagonists & inhibitors ; *Gene Editing ; Humans ; Moraxella/*genetics ; Pseudomonas/*genetics ; }, abstract = {Bacterial CRISPR-Cas systems protect their host from bacteriophages and other mobile genetic elements. Mobile elements, in turn, encode various anti-CRISPR (Acr) proteins to inhibit the immune function of CRISPR-Cas. To date, Acr proteins have been discovered for type I (subtypes I-D, I-E, and I-F) and type II (II-A and II-C) but not other CRISPR systems. Here, we report the discovery of 12 acr genes, including inhibitors of type V-A and I-C CRISPR systems. AcrVA1 inhibits a broad spectrum of Cas12a (Cpf1) orthologs-including MbCas12a, Mb3Cas12a, AsCas12a, and LbCas12a-when assayed in human cells. The acr genes reported here provide useful biotechnological tools and mark the discovery of acr loci in many bacteria and phages.}, } @article {pmid30190307, year = {2018}, author = {Watters, KE and Fellmann, C and Bai, HB and Ren, SM and Doudna, JA}, title = {Systematic discovery of natural CRISPR-Cas12a inhibitors.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {236-239}, pmid = {30190307}, issn = {1095-9203}, support = {K99 GM118909/GM/NIGMS NIH HHS/United States ; R00 GM118909/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*antagonists & inhibitors/chemistry/genetics/metabolism ; *CRISPR-Cas Systems ; Cell Line ; Computational Biology/methods ; DNA Cleavage ; Endonucleases/*antagonists & inhibitors ; *Gene Editing ; Genome, Bacterial ; Humans ; Moraxella/*genetics ; }, abstract = {Cas12a (Cpf1) is a CRISPR-associated nuclease with broad utility for synthetic genome engineering, agricultural genomics, and biomedical applications. Although bacteria harboring CRISPR-Cas9 or CRISPR-Cas3 adaptive immune systems sometimes acquire mobile genetic elements encoding anti-CRISPR proteins that inhibit Cas9, Cas3, or the DNA-binding Cascade complex, no such inhibitors have been found for CRISPR-Cas12a. Here we use a comprehensive bioinformatic and experimental screening approach to identify three different inhibitors that block or diminish CRISPR-Cas12a-mediated genome editing in human cells. We also find a widespread connection between CRISPR self-targeting and inhibitor prevalence in prokaryotic genomes, suggesting a straightforward path to the discovery of many more anti-CRISPRs from the microbial world.}, } @article {pmid30189900, year = {2018}, author = {Sado, M and Park, S and Ninomiya, A and Sato, Y and Fujisawa, D and Shirahase, J and Mimura, M}, title = {Feasibility study of mindfulness-based cognitive therapy for anxiety disorders in a Japanese setting.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {653}, pmid = {30189900}, issn = {1756-0500}, support = {H24 KEIO-GAKUSHIN-KOJIN 004163//School of Medicine, Keio University/ ; }, mesh = {Adult ; Aged ; Anxiety ; Anxiety Disorders/*therapy ; *Cognitive Behavioral Therapy ; Feasibility Studies ; Female ; Humans ; Middle Aged ; *Mindfulness ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {OBJECTIVE: Mindfulness-based cognitive therapy (MBCT) could be a treatment option for anxiety disorders. Although its effectiveness under conditions of low pharmacotherapy rates has been demonstrated, its effectiveness under condition of high pharmacotherapy rate is still unknown. The aim of the study was to evaluate effectiveness of MBCT under the context of high pharmacotherapy rates.

RESULTS: A single arm with pre-post comparison design was adopted. Those who had any diagnosis of anxiety disorders, between the ages of 20 and 74, were included. Participants attended 8 weekly 2-hour-long sessions followed by 2 monthly boosters. Evaluation was conducted at baseline, in the middle, at end of the intervention, and at follow-up. The State-Trait Anxiety Inventory (STAI)-state was set as the primary outcome. Pre-post analyses with mixed-effect models repeated measures were conducted. Fourteen patients were involved. The mean age was 45.0, and 71.4% were female. The mean change in the STAI-state at every point showed statistically significant improvement. The STAI-trait also showed improvement at a high significance level from the very early stages. The participants showed significant improvement at least one point in some other secondary outcomes. Trial registration Retrospectively registered at the University Hospital Medical Information Network on 1st August 2013 (ID: UMIN000011347).}, } @article {pmid30189892, year = {2018}, author = {Tigistu, M and Azale, T and Kebebe, H and Yihunie, T}, title = {Frequency of seizure attack and associated factors among patients with epilepsy at University of Gondar Referral Hospital: a cross-sectional study, Gondar, North West Ethiopia, 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {652}, pmid = {30189892}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Epilepsy/classification/*complications/*etiology ; Ethiopia ; Female ; Hospitals, University ; Humans ; Male ; Referral and Consultation ; Seizures ; Severity of Illness Index ; }, abstract = {OBJECTIVE: About three-fourth of adults with new-onset epilepsy become seizure-free with current anti-epileptic drugs, but around one-fourth of the patients continue to experience seizure which increases the risk of accident, disability, death and treatment side effects. Therefore, this study aimed to address the gap in determining the magnitude of the number of seizure attacks and identify the factors that provoke a repeated seizure in a patient with epilepsy.

RESULTS: A total of 166(40.68%) study participants were experienced seizure attacks with a minimum of one and a maximum of seventeen times attacks. Perceived exposure to noise (adjusted incidence risk ratio (AIRR) = 1.91, 95% confidence interval (CI) [1.46, 2.49]), light (AIRR = 1.48, 95% CI [1.09, 2.00]), head injury (AIRR = 1.71, 95% CI [1.14, 2.57]) and sleep deprivations (AIRR = 1.41, 95% CI [1.02, 1.94]) were associated with increased incidence of seizure, while adherence adjusted odds ratio (AOR) = 18.18, 95% CI [3.49, 94.63]), being in middle wealth index (AOR = 3.52, 95% CI [1.14, 11.02]) and being in rich wealth index (AOR = 4.05, 95% CI [1.54, 10.69]) were associated with inflation of zero count.}, } @article {pmid30189891, year = {2018}, author = {Thota, S}, title = {Initial value problems for system of differential-algebraic equations in Maple.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {651}, doi = {10.1186/s13104-018-3748-0}, pmid = {30189891}, issn = {1756-0500}, mesh = {*Algorithms ; *Software ; }, abstract = {OBJECTIVES: In this paper, we discuss a Maple package, deaSolve, of the symbolic algorithm for solving an initial value problem for the system of linear differential-algebraic equations with constant coefficients.

RESULTS: Using the proposed Maple package, one can compute the desired Green's function of a given IVP. Sample computations are presented to illustrate the Maple package.}, } @article {pmid30189863, year = {2018}, author = {Smith, SJ}, title = {Q&A: Array tomography.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {98}, pmid = {30189863}, issn = {1741-7007}, support = {R01 MH104227/MH/NIMH NIH HHS/United States ; R01 NS092474/NS/NINDS NIH HHS/United States ; }, abstract = {Array tomography encompasses light and electron microscopy modalities that offer unparalleled opportunities to explore three-dimensional cellular architectures in extremely fine structural and molecular detail. Fluorescence array tomography achieves much higher resolution and molecular multiplexing than most other fluorescence microscopy methods, while electron array tomography can capture three-dimensional ultrastructure much more easily and rapidly than traditional serial-section electron microscopy methods. A correlative fluorescence/electron microscopy mode of array tomography furthermore offers a unique capacity to merge the molecular discrimination strengths of multichannel fluorescence microscopy with the ultrastructural imaging strengths of electron microscopy. This essay samples the first decade of array tomography, highlighting applications in neuroscience.}, } @article {pmid30189862, year = {2018}, author = {Dong, ZG and Chen, YH and Ge, HX and Li, XY and Wu, HL and Wang, CH and Hu, Z and Wu, YJ and Fu, GH and Lu, JK and Che, H}, title = {Response of growth and development of the Pacific oyster (Crassostrea gigas) to thermal discharge from a nuclear power plant.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {31}, pmid = {30189862}, issn = {1472-6785}, abstract = {BACKGROUND: During electricity generation of nuclear power plant, heat energy cannot be completely converted into electrical energy, and a part of it is lost in the form of thermal discharge into the environment. The thermal discharge is harmful to flora and fauna leading to environmental deterioration, biological diversity decline, and even biological extinction.

RESULTS: The present study investigated the influence of thermal discharge from a nuclear power plant on the growth and development of Pacific oyster Crassostrea gigas which is widely used as bio indicator to monitor environmental changes. The growth of soft part and the gonad development of oysters were inhibited due to thermal discharge. During winter season, temperature elevation caused by thermal discharge promoted the growth of oyster shells. During summer season, the growth rate of oysters in thermal discharge area was significantly lower than that of the natural sea area.

CONCLUSIONS: The results of this study provided a better understanding of assessing the impact of thermal discharge on the marine ecological environment and mariculture industry. It also provided a scientific basis for defining a safe zone for aquaculture in the vicinity of nuclear power plants.}, } @article {pmid30189859, year = {2018}, author = {Szopinska, JW and Gresse, R and van der Marel, S and Boekhorst, J and Lukovac, S and van Swam, I and Franke, B and Timmerman, H and Belzer, C and Arias Vasquez, A}, title = {Reliability of a participant-friendly fecal collection method for microbiome analyses: a step towards large sample size investigation.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {110}, pmid = {30189859}, issn = {1471-2180}, abstract = {BACKGROUND: The effects of gut microbiota on human traits are expected to be small to moderate and adding the complexity of the human diseases, microbiome research demands big sample sizes. Fecal samples for such studies are mostly self-collected by participants at home. This imposes an extra level of complexity as sample collection and storage can be challenging. Effective, low-burden collection and storage methods allowing fecal samples to be transported properly and ensuring optimal quality and quantity of bacterial DNA for upstream analyses are necessary. Moreover, accurate assessment of the microbiome composition also depends on bacterial DNA extraction method. The aim of this study was to evaluate the reliability and efficiency of the OMNIgene•GUT kit as a participant-fecal friendly collection method (storage at room temperature for 24 h (O24h) or 7 days (O7d)) in comparison to the standard collection method (Fresh, storage at 4 °C for less than 24 h) in terms of amount of variability and information content accounting for two common DNA extraction methods.

RESULTS: Fourteen fecal samples were collected from healthy individuals (7 males, 7 females). Collection and storage methods did not differ significantly in terms of DNA concentration and Shannon diversity index. Phylum relative abundance showed significant differences for Bacteroidetes, Actinobacteria and Cyanobacteria. The differences were observed between control (Fresh) and O24h methods, but not between Fresh and O7d. These differences were not seen when performing bacterial DNA quantification based on three bacterial groups: Bacteroides spp., Bifidobacterium spp. and Clostridium cluster IV, which represent three major phyla: Bacteroidetes, Actinobacteria and Firmicutes respectively. The two DNA extraction methods differ in terms of DNA quantity, quality, bacterial diversity and bacterial relative abundance. Furthermore, principal component analysis revealed differences in microbial structure, which are driven by the DNA extraction methods more than the collection/storage methods.

CONCLUSION: Our results have highlighted the potential of using the OMNIgene•GUT kit for collection and storage at ambient temperature, which is convenient for studies aiming to collect large samples by giving participants the possibility to send samples by post. Importantly, we revealed that the choice of DNA extraction method have an impact on the microbiome profiling.}, } @article {pmid30189856, year = {2018}, author = {Tóth, V and Lakatos, F}, title = {Phylogeographic pattern of the plane leaf miner, Phyllonorycter platani (STAUDINGER, 1870) (Lepidoptera: Gracillariidae) in Europe.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {135}, pmid = {30189856}, issn = {1471-2148}, support = {12-1-2013-0034//VKSZ/International ; STSM-FP1002-10569//COST/International ; 4.2.2.B-10/1-2010-0018//TAMOP/International ; 4.2.1.B-09/1/KONV//TAMOP/International ; }, mesh = {Alleles ; Animals ; Base Sequence ; DNA, Ribosomal/genetics ; Electron Transport Complex IV/genetics ; Europe ; Genetic Markers ; Genetic Variation ; Haplotypes/genetics ; Lepidoptera/*classification/genetics ; Phylogeny ; *Phylogeography ; Plant Leaves/*parasitology ; }, abstract = {BACKGROUND: The plane leaf miner, Phyllonorycter platani is a widely distributed insect species on plane trees and has a well-documented colonisation history in Europe over the last century. However, phylogeographic data of the species are lacking.

RESULTS: We analysed 284 individuals from 38 populations across Europe, Asia, and North America. A 1242 bp fragment of the mitochondrial COI gene and an 893 bp fragment of the 28S rDNA has been Sanger sequenced. Twenty-four haplotypes were detected on the COI gene, and two alleles were identified on the 28S rDNA. We revealed two distinct clades for both markers reflecting the geographic origins, Asia and Europe. The genetic distance between the two main clades is 2.08% on the COI gene and 0.10% on the nuclear DNA. An overlapping zone of the two clades was found across Eastern Europe and the Anatolian Peninsula. We detected heterozygote individuals of the 28S rDNA gene in Moldavia, Ukraine and in the southern part of Turkey. These suggest that the two clades can hybridise. Furthermore, the presence of European type homozygote individuals has been confirmed in the southern part of Turkey as well.

CONCLUSIONS: We have shown that both post-glacial recolonization and recent expansion events influenced the present genetic structure of P. platani. The genetic patterns revealed at least two refugia during the last ice age: one in the Balkan Peninsula and the other in the Caucasus region. Recent expansion was detected in some European and Central Asian populations. The two main clades (Europe/Asia) show definite genetic differences; however, several hybrid individuals were found in the overlapping zone as well (stretching over Eastern Europe and the Anatolian Peninsula). Discrepancies in mitochondrial and nuclear data indicate introgressions in the southern part of the Anatolian Peninsula.}, } @article {pmid30189851, year = {2018}, author = {Sun, H and Shen, Y and Luo, G and Cai, Y and Xiang, Z}, title = {An integrated strategy for identifying new targets and inferring the mechanism of action: taking rhein as an example.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {315}, pmid = {30189851}, issn = {1471-2105}, support = {81773691//National Natural Science Foundation of China/ ; ZS2017018//Wenzhou Science and Technology Major Project/ ; }, mesh = {Anthraquinones/*pharmacology ; Computational Biology/*methods ; Drug Discovery/*methods ; Enzyme Inhibitors/*pharmacology ; Humans ; Pharmacology/*methods ; *Protein Interaction Maps ; Proteins/*metabolism ; }, abstract = {BACKGROUND: Target identification is necessary for the comprehensive inference of the mechanism of action of a compound. The application of computational methods to predict the targets of bioactive compounds saves cost and time in drug research and development. Therefore, we designed an integrated strategy consisting of ligand-protein docking, network analysis, enrichment analysis, and an experimental surface plasmon resonance (SPR) method to identify and validate new targets, and then used enriched pathways to elucidate the underlying pharmacological mechanisms. Here, we used rhein, a compound with various pharmacological activities, as an example to find some of its previously unknown targets and to determine its pharmacological activity.

RESULTS: A total of nine candidate targets were discovered, including LCK, HSP90AA1, RAB5A, EGFR, CDK2, CDK6, GSK3B, p38, and JNK. LCK was confirmed through SPR experiments, and HSP90AA1, EGFR, CDK6, p38, and JNK were validated through previous reports. Rhein network regulations are complex and interconnected. The therapeutic effect of rhein is the synergistic and comprehensive result of this vast and complex network, and the perturbation of multiple targets gives rhein its various pharmacological activities.

CONCLUSIONS: This study provided a new integrated strategy to identify new targets of bioactive compounds and reveal their molecular mechanisms of action.}, } @article {pmid30189848, year = {2018}, author = {Fattorini, L and Hause, B and Gutierrez, L and Veloccia, A and Della Rovere, F and Piacentini, D and Falasca, G and Altamura, MM}, title = {Jasmonate promotes auxin-induced adventitious rooting in dark-grown Arabidopsis thaliana seedlings and stem thin cell layers by a cross-talk with ethylene signalling and a modulation of xylogenesis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {182}, pmid = {30189848}, issn = {1471-2229}, support = {RP116154C3D60B9D//Ateneo Project Sapienza Università di Roma/ ; RG11715C775A7FE9//Ateneo Project Sapienza Università di Roma/ ; }, mesh = {Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins/genetics ; Cyclopentanes/*pharmacology ; Darkness ; Ethylenes/metabolism ; Indoleacetic Acids ; Oxylipins/*pharmacology ; Plant Cells/physiology ; Plant Roots/*growth & development ; Plant Stems/cytology/*growth & development ; Seedlings/growth & development ; Signal Transduction ; Transcription Factors/genetics ; Xylem/*growth & development ; }, abstract = {BACKGROUND: Adventitious roots (ARs) are often necessary for plant survival, and essential for successful micropropagation. In Arabidopsis thaliana dark-grown seedlings AR-formation occurs from the hypocotyl and is enhanced by application of indole-3-butyric acid (IBA) combined with kinetin (Kin). The same IBA + Kin-treatment induces AR-formation in thin cell layers (TCLs). Auxin is the main inducer of AR-formation and xylogenesis in numerous species and experimental systems. Xylogenesis is competitive to AR-formation in Arabidopsis hypocotyls and TCLs. Jasmonates (JAs) negatively affect AR-formation in de-etiolated Arabidopsis seedlings, but positively affect both AR-formation and xylogenesis in tobacco dark-grown IBA + Kin TCLs. In Arabidopsis the interplay between JAs and auxin in AR-formation vs xylogenesis needs investigation. In de-etiolated Arabidopsis seedlings, the Auxin Response Factors ARF6 and ARF8 positively regulate AR-formation and ARF17 negatively affects the process, but their role in xylogenesis is unknown. The cross-talk between auxin and ethylene (ET) is also important for AR-formation and xylogenesis, occurring through EIN3/EIL1 signalling pathway. EIN3/EIL1 is the direct link for JA and ET-signalling. The research investigated JA role on AR-formation and xylogenesis in Arabidopsis dark-grown seedlings and TCLs, and the relationship with ET and auxin. The JA-donor methyl-jasmonate (MeJA), and/or the ET precursor 1-aminocyclopropane-1-carboxylic acid were applied, and the response of mutants in JA-synthesis and -signalling, and ET-signalling investigated. Endogenous levels of auxin, JA and JA-related compounds, and ARF6, ARF8 and ARF17 expression were monitored.

RESULTS: MeJA, at 0.01 μM, enhances AR-formation, when combined with IBA + Kin, and the response of the early-JA-biosynthesis mutant dde2-2 and the JA-signalling mutant coi1-16 confirmed this result. JA levels early change during TCL-culture, and JA/JA-Ile is immunolocalized in AR-tips and xylogenic cells. The high AR-response of the late JA-biosynthesis mutant opr3 suggests a positive action also of 12-oxophytodienoic acid on AR-formation. The crosstalk between JA and ET-signalling by EIN3/EIL1 is critical for AR-formation, and involves a competitive modulation of xylogenesis. Xylogenesis is enhanced by a MeJA concentration repressing AR-formation, and is positively related to ARF17 expression.

CONCLUSIONS: The JA concentration-dependent role on AR-formation and xylogenesis, and the interaction with ET opens the way to applications in the micropropagation of recalcitrant species.}, } @article {pmid30189845, year = {2018}, author = {Yuan, N and Rai, KM and Balasubramanian, VK and Upadhyay, SK and Luo, H and Mendu, V}, title = {Genome-wide identification and characterization of LRR-RLKs reveal functional conservation of the SIF subfamily in cotton (Gossypium hirsutum).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {185}, pmid = {30189845}, issn = {1471-2229}, support = {18-092//Cotton Incorporated/ ; }, mesh = {Adaptation, Physiological/genetics ; Arabidopsis/genetics ; Evolution, Molecular ; Exons ; Gene Ontology ; Gene Silencing ; Genes, Plant ; Gossypium/classification/*enzymology/genetics ; Introns ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Protein Conformation ; Protein Kinases/chemistry/*genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: As one of the largest subfamilies of the receptor-like protein kinases (RLKs) in plants, Leucine Rich Repeats-RLKs (LRR-RLKs) are involved in many critical biological processes including growth, development and stress responses in addition to various physiological roles. Arabidopsis contains 234 LRR-RLKs, and four members of Stress Induced Factor (SIF) subfamily (AtSIF1-AtSIF4) which are involved in abiotic and biotic stress responses. Herein, we aimed at identification and functional characterization of SIF subfamily in cultivated tetraploid cotton Gossypium hirsutum.

RESULTS: Genome-wide analysis of cotton LRR-RLK gene family identified 543 members and phylogenetic analysis led to the identification of 6 cotton LRR-RLKs with high homology to Arabidopsis SIFs. Of the six SIF homologs, GhSIF1 is highly conserved exhibiting 46-47% of homology with AtSIF subfamily in amino acid sequence. The GhSIF1 was transiently silenced using Virus-Induced Gene Silencing system specifically targeting the 3' Untranslated Region. The transiently silenced cotton seedlings showed enhanced salt tolerance compared to the control plants. Further, the transiently silenced plants showed better growth, lower electrolyte leakage, and higher chlorophyll and biomass contents.

CONCLUSIONS: Overall, 543 LRR-RLK genes were identified using genome-wide analysis in cultivated tetraploid cotton G. hirsutum. The present investigation also demonstrated the conserved salt tolerance function of SIF family member in cotton. The GhSIF1 gene can be knocked out using genome editing technologies to improve salt tolerance in cotton.}, } @article {pmid30189844, year = {2018}, author = {Schneider, M and Knuesting, J and Birkholz, O and Heinisch, JJ and Scheibe, R}, title = {Cytosolic GAPDH as a redox-dependent regulator of energy metabolism.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {184}, pmid = {30189844}, issn = {1471-2229}, support = {SFB 944//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cysteine/metabolism ; Cytosol/*metabolism ; Energy Metabolism ; Genetic Complementation Test ; Glucosephosphate Dehydrogenase/genetics/metabolism ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/genetics/*metabolism ; Mitochondria/metabolism ; Mutation ; Oxidation-Reduction ; Schizosaccharomyces pombe Proteins/genetics/metabolism ; Thioredoxins/metabolism ; Voltage-Dependent Anion Channels/metabolism ; }, abstract = {BACKGROUND: Plant cytosolic NAD-dependent glyceraldehyde-3-phosphate dehydrogenase (GapC) displays redox-dependent changes in its subcellular localizations and activity. Apart from its fundamental role in glycolysis, it also exhibits moonlighting properties. Since the exceptional redox-sensitivity of GapC has been suggested to play a crucial role in its various functions, we here studied its redox-dependent subcellular localization and the influence of the redox-state on GapC protein interactions.

RESULTS: In mesophyll protoplasts from Arabidopsis thaliana, colocalization of GapC with mitochondria was more pronounced under reducing conditions than upon oxidative stress. In accordance, reduced GapC showed an increased affinity to the mitochondrial voltage-dependent anion-selective channel (VDAC) compared to the oxidized one. On the other hand, nuclear localization of GapC was increased under oxidizing conditions. The essential role of the catalytic cysteine for nuclear translocation was shown by using the corresponding cysteine mutants. Furthermore, interaction of GapC with the thioredoxin Trx-h3 as a candidate to revert the redox-modifications, occurred in the nucleus of oxidized protoplasts. In a yeast complementation assay, we could demonstrate that the plant-specific non-phosphorylating glyceraldehyde 3-P dehydrogenase (GapN) can substitute for glucose 6-P dehydrogenase to generate NADPH for re-reduction of the Trx system and ROS defense.

CONCLUSIONS: The preferred association of reduced, glycolytically active GapC with VDAC suggests a substrate-channeling metabolon at the mitochondrial surface for efficient energy generation. Increased occurrence of oxidized GapC in the nucleus points to a function in signal transduction and gene expression. Furthermore, the interaction of GapC with Trx-h3 in the nucleus indicates reversal of the oxidative cysteine modification after re-establishment of cellular homeostasis. Both, energy metabolism and signal transfer for long-term adjustment and protection from redox-imbalances are mediated by the various functions of GapC. The molecular properties of GapC as a redox-switch are key to its multiple roles in orchestrating energy metabolism.}, } @article {pmid30189843, year = {2018}, author = {Lichocka, M and Rymaszewski, W and Morgiewicz, K and Barymow-Filoniuk, I and Chlebowski, A and Sobczak, M and Samuel, MA and Schmelzer, E and Krzymowska, M and Hennig, J}, title = {Nucleus- and plastid-targeted annexin 5 promotes reproductive development in Arabidopsis and is essential for pollen and embryo formation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {183}, pmid = {30189843}, issn = {1471-2229}, support = {2012/05/B/NZ9/00984//Polish National Science Centre/ ; }, mesh = {Annexin A5/genetics/*physiology ; Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins/genetics/pharmacology/*physiology ; Cell Nucleus/*metabolism ; Chlorophyll/metabolism ; Chloroplast Proteins/genetics/*pharmacology ; Gene Knockdown Techniques ; Genes, Plant ; Homeostasis ; Plastids/*physiology ; Pollen/anatomy & histology/genetics/*growth & development ; Pollen Tube/growth & development ; Seedlings/metabolism ; Tobacco/genetics/physiology ; Transcriptome ; rab1 GTP-Binding Proteins/genetics/*pharmacology ; }, abstract = {BACKGROUND: Pollen development is a strictly controlled post-meiotic process during which microspores differentiate into microgametophytes and profound structural and functional changes occur in organelles. Annexin 5 is a calcium- and lipid-binding protein that is highly expressed in pollen grains and regulates pollen development and physiology. To gain further insights into the role of ANN5 in Arabidopsis development, we performed detailed phenotypic characterization of Arabidopsis plants with modified ANN5 levels. In addition, interaction partners and subcellular localization of ANN5 were analyzed to investigate potential functions of ANN5 at cellular level.

RESULTS: Here, we report that RNAi-mediated suppression of ANN5 results in formation of smaller pollen grains, enhanced pollen lethality, and delayed pollen tube growth. ANN5 RNAi knockdown plants also displayed aberrant development during the transition from the vegetative to generative phase and during embryogenesis, reflected by delayed bolting time and reduced embryo size, respectively. At the subcellular level, ANN5 was delivered to the nucleus, nucleolus, and cytoplasm, and was frequently localized in plastid nucleoids, suggesting a likely role in interorganellar communication. Furthermore, ANN5-YFP co-immunoprecipitated with RABE1b, a putative GTPase, and interaction in planta was confirmed in plastidial nucleoids using FLIM-FRET analysis.

CONCLUSIONS: Our findings let us to propose that ANN5 influences basal cell homeostasis via modulation of plastid activity during pollen maturation. We hypothesize that the role of ANN5 is to orchestrate the plastidial and nuclear genome activities via protein-protein interactions however not only in maturing pollen but also during the transition from the vegetative to the generative growth and seed development.}, } @article {pmid30189838, year = {2018}, author = {Servant, N and Varoquaux, N and Heard, E and Barillot, E and Vert, JP}, title = {Effective normalization for copy number variation in Hi-C data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {313}, pmid = {30189838}, issn = {1471-2105}, support = {ERC-250367//ERC Advanced Investigator award/ ; SMAC-ERC-280032//European Research Coucil/ ; ANR-11-BINF-0001//Agence Nationale de la Recherche/ ; }, mesh = {*Chromosome Aberrations ; *Chromosome Mapping ; Computational Biology/*standards ; *DNA Copy Number Variations ; *Genome, Human ; Genomics/*methods ; Humans ; Neoplasms/*genetics ; }, abstract = {BACKGROUND: Normalization is essential to ensure accurate analysis and proper interpretation of sequencing data, and chromosome conformation capture data such as Hi-C have particular challenges. Although several methods have been proposed, the most widely used type of normalization of Hi-C data usually casts estimation of unwanted effects as a matrix balancing problem, relying on the assumption that all genomic regions interact equally with each other.

RESULTS: In order to explore the effect of copy-number variations on Hi-C data normalization, we first propose a simulation model that predict the effects of large copy-number changes on a diploid Hi-C contact map. We then show that the standard approaches relying on equal visibility fail to correct for unwanted effects in the presence of copy-number variations. We thus propose a simple extension to matrix balancing methods that model these effects. Our approach can either retain the copy-number variation effects (LOIC) or remove them (CAIC). We show that this leads to better downstream analysis of the three-dimensional organization of rearranged genomes.

CONCLUSIONS: Taken together, our results highlight the importance of using dedicated methods for the analysis of Hi-C cancer data. Both CAIC and LOIC methods perform well on simulated and real Hi-C data sets, each fulfilling different needs.}, } @article {pmid30189836, year = {2018}, author = {Cai, Z and Guldbrandtsen, B and Lund, MS and Sahana, G}, title = {Prioritizing candidate genes post-GWAS using multiple sources of data for mastitis resistance in dairy cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {656}, pmid = {30189836}, issn = {1471-2164}, support = {0603-00519B//Innovationsfonden/ ; }, mesh = {Animals ; Cattle ; *Dairying ; Disease Resistance/*genetics ; *Genome-Wide Association Study ; Mastitis, Bovine/*genetics/*immunology ; Mutation ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: Improving resistance to mastitis, one of the costliest diseases in dairy production, has become an important objective in dairy cattle breeding. However, mastitis resistance is influenced by many genes involved in multiple processes, including the response to infection, inflammation, and post-infection healing. Low genetic heritability, environmental variations, and farm management differences further complicate the identification of links between genetic variants and mastitis resistance. Consequently, studies of the genetics of variation in mastitis resistance in dairy cattle lack agreement about the responsible genes.

RESULTS: We associated 15,552,968 imputed whole-genome sequencing markers for 5147 Nordic Holstein cattle with mastitis resistance in a genome-wide association study (GWAS). Next, we augmented P-values for markers in genes in the associated regions using Gene Ontology terms, Kyoto Encyclopedia of Genes and Genomes pathway analysis, and mammalian phenotype database. To confirm results of gene-based analyses, we used gene expression data from E. coli-challenged cow udders. We identified 22 independent quantitative trait loci (QTL) that collectively explained 14% of the variance in breeding values for resistance to clinical mastitis (CM). Using association test statistics with multiple pieces of independent information on gene function and differential expression during bacterial infection, we suggested putative causal genes with biological relevance for 12 QTL affecting resistance to CM in dairy cattle.

CONCLUSION: Combining information on the nearest positional genes, gene-based analyses, and differential gene expression data from RNA-seq, we identified putative causal genes (candidate genes with biological evidence) in QTL for mastitis resistance in Nordic Holstein cattle. The same strategy can be applied for other traits.}, } @article {pmid30189834, year = {2018}, author = {Ren, D and Gong, S and Shu, J and Zhu, J and Liu, H and Chen, P}, title = {Effects of mixed lactic acid bacteria on intestinal microbiota of mice infected with Staphylococcus aureus.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {109}, pmid = {30189834}, issn = {1471-2180}, abstract = {BACKGROUND: The stability of intestinal microorganisms plays an important role in human health, as the intestines perform important functions in the human body. Staphylococcus aureus is a Gram-positive, facultative anaerobic bacteria, it causes human infection worldwide, and is a major pathogen that causes intestinal infection. Mixed lactic acid bacteria (LAB) may have potential in the prevention and treatment of S. aureus infection. In the present study, we examined the effects of mixed LAB treatment on intestinal microbiota modulation in mice infected with S. aureus.

RESULTS: High-throughput sequencing of the V3-V4 region of the bacterial 16S rRNA gene showed that the mixed LAB maintained the richness and diversity of the microbiota in the mouse intestine. By establishing operational taxonomic units and using rarefaction analysis, rank-abundance distribution curves, heat maps, Venn diagrams, bacterial community structures, and hierarchical clustering analysis, Bacteroidales, Lachnospiraceae, Bacteroides and Prevotellaceae were the most abundant taxa in the samples, we found that the composition of the intestinal microbiota was similar between the protection group administered mixed LAB and the negative control group.

CONCLUSIONS: Staphylococcus aureus destroys the stable intestinal microbiota structure of mice, treatment with mixed LAB could prevent S. aureus infection in mice and improve the structure of the intestinal microbiota.}, } @article {pmid30189833, year = {2018}, author = {Tello, M and Avalos, F and Orellana, O}, title = {Codon usage and modular interactions between messenger RNA coding regions and small RNAs in Escherichia coli.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {657}, pmid = {30189833}, issn = {1471-2164}, support = {1150834//FONDECYT/ ; USA1799//Universidad de Santiago de Chile/ ; }, mesh = {Codon/*genetics ; Escherichia coli/*genetics ; RNA, Bacterial/*genetics ; RNA, Messenger/genetics ; RNA, Small Untranslated/*genetics ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Small RNAs (sRNAs) are key regulators of gene expression in bacteria. In addition to modulating translation initiation, sRNAs can interact with mRNA coding regions to regulate mRNA stability and translation efficiency, enhancing or impeding progression of the ribosome along the mRNA. Since most amino acids are decoded by more than one codon (synonymous) we asked as to whether there is a codon bias in the interaction of sRNAs with coding regions of mRNAs. Therefore, we explored whether there are differences in codon usage or tRNA availability according to whether an mRNA is regulated by sRNAs or not. We also explored these parameters in the coding interaction regions in mRNAs. We focused our analysis on sRNAs that regulate multiple mRNAs.

RESULTS: We found differences in codon adaptation index and tRNA adaptation index between sRNA-regulated and non-sRNA-regulated mRNAs. Interestingly, the sRNA-mRNA interacting regions tended to be enriched in unpreferred codons decoded by scarce tRNAs. We also found that sRNAs with multiple targets often contained modular segments capable of recognizing conserved motifs among these mRNAs.

CONCLUSIONS: Our results show that sRNAs in E. coli tend to recognize mRNA coding regions in which the ribosome is predicted to advance at low speeds. Identified motifs in interacting regions are conserved among mRNAs that are recognized by the same sRNA.}, } @article {pmid30189832, year = {2018}, author = {Bazzoli, C and Lambert-Lacroix, S}, title = {Classification based on extensions of LS-PLS using logistic regression: application to clinical and multiple genomic data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {314}, pmid = {30189832}, issn = {1471-2105}, mesh = {Algorithms ; Datasets as Topic ; *Gene Expression Profiling ; *Genome, Human ; Genomics/*methods ; Humans ; *Least-Squares Analysis ; Logistic Models ; Neoplasms/*classification/genetics ; }, abstract = {BACKGROUND: To address high-dimensional genomic data, most of the proposed prediction methods make use of genomic data alone without considering clinical data, which are often available and known to have predictive value. Recent studies suggest that combining clinical and genomic information may improve predictions. We consider here methods for classification purposes that simultaneously use both types of variables but apply dimensionality reduction only to the high-dimensional genomic ones.

RESULTS: Using partial least squares (PLS), we propose some one-step approaches based on three extensions of the least squares (LS)-PLS method for logistic regression. A comparison of their prediction performances via a simulation and on real data sets from cancer studies is conducted.

CONCLUSION: In general, those methods using only clinical data or only genomic data perform poorly. The advantage of using LS-PLS methods for classification and their performances are shown and then used to analyze clinical and genomic data. The corresponding prediction results are encouraging and stable regardless of the data set and/or number of selected features. These extensions have been implemented in the R package lsplsGlm to enhance their use.}, } @article {pmid30189831, year = {2018}, author = {Vásquez-Piñeros, MA and Martínez-Lavanchy, PM and Jehmlich, N and Pieper, DH and Rincón, CA and Harms, H and Junca, H and Heipieper, HJ}, title = {Delftia sp. LCW, a strain isolated from a constructed wetland shows novel properties for dimethylphenol isomers degradation.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {108}, pmid = {30189831}, issn = {1471-2180}, abstract = {BACKGROUND: Dimethylphenols (DMP) are toxic compounds with high environmental mobility in water and one of the main constituents of effluents from petro- and carbochemical industry. Over the last few decades, the use of constructed wetlands (CW) has been extended from domestic to industrial wastewater treatments, including petro-carbochemical effluents. In these systems, the main role during the transformation and mineralization of organic pollutants is played by microorganisms. Therefore, understanding the bacterial degradation processes of isolated strains from CWs is an important approach to further improvements of biodegradation processes in these treatment systems.

RESULTS: In this study, bacterial isolation from a pilot scale constructed wetland fed with phenols led to the identification of Delftia sp. LCW as a DMP degrading strain. The strain was able to use the o-xylenols 3,4-DMP and 2,3-DMP as sole carbon and energy sources. In addition, 3,4-DMP provided as a co-substrate had an effect on the transformation of other four DMP isomers. Based on the detection of the genes, proteins, and the inferred phylogenetic relationships of the detected genes with other reported functional proteins, we found that the phenol hydroxylase of Delftia sp. LCW is induced by 3,4-DMP and it is responsible for the first oxidation of the aromatic ring of 3,4-, 2,3-, 2,4-, 2,5- and 3,5-DMP. The enzyme may also catalyze both monooxygenation reactions during the degradation of benzene. Proteome data led to the identification of catechol meta cleavage pathway enzymes during the growth on ortho DMP, and validated that cleavage of the aromatic rings of 2,5- and 3,5-DMPs does not result in mineralization. In addition, the tolerance of the strain to high concentrations of DMP, especially to 3,4-DMP was higher than that of other reported microorganisms from activated sludge treating phenols.

CONCLUSIONS: LCW strain was able to degraded complex aromatics compounds. DMPs and benzene are reported for the first time to be degraded by a member of Delftia genus. In addition, LCW degraded DMPs with a first oxidation of the aromatic rings by a phenol hydroxylase, followed by a further meta cleavage pathway. The higher resistance to DMP toxicity, the ability to degrade and transform DMP isomers and the origin as a rhizosphere bacterium from wastewater systems, make LCW a suitable candidate to be used in bioremediation of complex DMP mixtures in CWs systems.}, } @article {pmid30189319, year = {2018}, author = {Dahn, HA and Strickland, JL and Osorio, A and Colston, TJ and Parkinson, CL}, title = {Hidden diversity within the depauperate genera of the snake tribe Lampropeltini (Serpentes, Colubridae).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {214-225}, doi = {10.1016/j.ympev.2018.08.018}, pmid = {30189319}, issn = {1095-9513}, abstract = {Accurate representation of lineage diversity through complete taxon sampling is crucial to understanding the evolution of biodiversity, particularly when using molecular phylogenetics to estimate evolutionary relationships. In this interest, taxonomic diversity is often used as a proxy for lineage diversity even though the two concepts are not synonymous. We explore this within the snake tribe Lampropeltini which includes some of the most conspicuous and heavily studied snakes in North America. Both the taxonomy and hypothesized relationships within this tribe have been in flux. The number of species has increased from 23 to 51 over the last thirty years, predominately within three of the nine genera (Lampropeltis, Pantherophis, Pituophis). The remaining six depauperate genera (Arizona, Bogertophis, Cemophora, Pseudelaphe, Rhinocheilus, and Senticolis) have been poorly represented in phylogenetic studies. To estimate evolutionary relationships and determine if the dichotomy in depauperate and speciose genera within Lampropeltini is a function of taxon sampling or truly represents the lineage diversity, we estimated the phylogeny of this group using nuclear and mitochondrial loci in a concatenated and coalescent framework with the largest sampling of the six depauperate genera to date. In addition, we estimated the divergence dates among the genera to assess whether the instability of Lampropeltini phylogenetic relationships is due to an adaptive radiation. While some nodes still remain unresolved, the generic-level relationships we recovered agree with those of a recent next-generation study that used a much larger set of loci for fewer individuals. We also tested two putative species, Arizona pacata and Pseudelaphe phaescens, for the first time phylogenetically and find evidence that they are distinct lineages. Overall, we find that the taxonomic and genetic diversity are not correlated in Lampropeltini and that representing putative diversity in phylogenies will lead to a better estimate of evolutionary histories, especially in groups with complex radiations.}, } @article {pmid30189195, year = {2018}, author = {Rabadi, MM and Abdulmahdi, W and Nesi, L and Jules, E and Marghani, Y and Sheinin, E and Tilzer, J and Gupta, S and Chen, S and Cassimatis, ND and Lipphardt, M and Kozlowski, PB and Ratliff, BB}, title = {Maternal malnourishment induced upregulation of fetuin-B blunts nephrogenesis in the low birth weight neonate.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {78-91}, doi = {10.1016/j.ydbio.2018.09.001}, pmid = {30189195}, issn = {1095-564X}, mesh = {Animals ; Apoptosis/physiology ; Embryonic Stem Cells/metabolism ; Female ; Fetal Nutrition Disorders/genetics/*metabolism ; Fetuin-B/*metabolism ; Homeodomain Proteins/metabolism ; Infant, Low Birth Weight/physiology ; Kidney/*embryology/metabolism ; Male ; Maternal Health ; Mice ; Nephrons/embryology/metabolism ; Oxidative Stress/physiology ; Pregnancy ; Primary Cell Culture ; Transcription Factors/metabolism ; Up-Regulation ; }, abstract = {Maternal undernutrition during pregnancy (MUN) often leads to low birth weight (LBW) neonates that have a reduced total nephron endowment, leaving these neonates susceptible to kidney disease throughout their lives. For reasons unknown, these LBW neonates have impaired kidney development due to a severe reduction in renal SIX2+ stem cells during nephrogenesis. Using a mouse model of MUN, we investigated SIX2+ stem cell reduction in the LBW neonate. Significant upregulation of the protein fetuin-B (measured by PCR and immunoblotting) in the MUN mother's placenta, organs and circulation yielded a 3-fold increase of this protein in the embryonic kidney. Recombinant fetuin-B, administered to healthy pregnant mothers at the concentration equivalent to that in the MUN mother, crossed the placenta and reduced both SIX2+ stem cells by 50% and nephron formation by 66% in embryonic kidneys (measured by immunofluorescence and the physical dissector/fractionator stereological method). Administration of fetuin-B to kidney explants yielded similar reductions in renal SIX2+ stem cells and nephron formation. Fetuin-B treatment of isolated embryonic renal SIX2+ stem cell primary cultures 1) increased NF-kB activity and apoptosis, 2) reduced cell proliferation due to upregulated p21 nuclear activity and subsequent cell cycle arrest, and 3) enhanced generation of reactive oxygen species (measured by fluorescence microscopy). In conclusion, MUN increases fetuin-B in the developing embryonic kidney. The increase in fetuin-B blunts nephrogenesis by reducing SIX2+ stem cells by promoting their apoptosis (via NF-kB upregulation), blunting their proliferative renewal (via p21 upregulation) and enhancing oxidative stress.}, } @article {pmid30188995, year = {2018}, author = {Shibl, AA and Ngugi, DK and Talarmin, A and Thompson, LR and Blom, J and Stingl, U}, title = {The genome of a novel isolate of Prochlorococcus from the Red Sea contains transcribed genes for compatible solute biosynthesis.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy182}, pmid = {30188995}, issn = {1574-6941}, abstract = {Marine microbes possess genomic and physiological adaptations to cope with varying environmental conditions. So far, the effects of high salinity on the most abundant marine photoautotrophic organism, Prochlorococcus, in marine oligotrophic environments, are mostly unknown. Here, we report the isolation of a new Prochlorococcus strain (RSP50) belonging to high-light (HL) clade II from the Red Sea, one of the warmest and most saline bodies of water in the global oceans. A comparative genomic analysis identified a set of 59 genes that were exclusive to RSP50 relative to currently available Prochlorococcus genomes, the majority of which (70%) encode for hypothetical proteins of unknown function. However, three of the unique genes encode for a complete pathway for the biosynthesis of the compatible solute glucosylglycerol, and are homologous to enzymes found in the sister lineage Synechococcus. Metatranscriptomic analyses of this metabolic pathway in the water column of the Red Sea revealed that the corresponding genes were constitutively transcribed, independent of depth and light, suggesting that osmoregulation using glucosylglycerol is a general feature of HL II Prochlorococcus in the Red Sea.}, } @article {pmid30188496, year = {2018}, author = {Adli, E and Ahuja, A and Apsimon, O and Apsimon, R and Bachmann, AM and Barrientos, D and Batsch, F and Bauche, J and Berglyd Olsen, VK and Bernardini, M and Bohl, T and Bracco, C and Braunmüller, F and Burt, G and Buttenschön, B and Caldwell, A and Cascella, M and Chappell, J and Chevallay, E and Chung, M and Cooke, D and Damerau, H and Deacon, L and Deubner, LH and Dexter, A and Doebert, S and Farmer, J and Fedosseev, VN and Fiorito, R and Fonseca, RA and Friebel, F and Garolfi, L and Gessner, S and Gorgisyan, I and Gorn, AA and Granados, E and Grulke, O and Gschwendtner, E and Hansen, J and Helm, A and Henderson, JR and Hüther, M and Ibison, M and Jensen, L and Jolly, S and Keeble, F and Kim, SY and Kraus, F and Li, Y and Liu, S and Lopes, N and Lotov, KV and Maricalva Brun, L and Martyanov, M and Mazzoni, S and Medina Godoy, D and Minakov, VA and Mitchell, J and Molendijk, JC and Moody, JT and Moreira, M and Muggli, P and Öz, E and Pasquino, C and Pardons, A and Peña Asmus, F and Pepitone, K and Perera, A and Petrenko, A and Pitman, S and Pukhov, A and Rey, S and Rieger, K and Ruhl, H and Schmidt, JS and Shalimova, IA and Sherwood, P and Silva, LO and Soby, L and Sosedkin, AP and Speroni, R and Spitsyn, RI and Tuev, PV and Turner, M and Velotti, F and Verra, L and Verzilov, VA and Vieira, J and Welsch, CP and Williamson, B and Wing, M and Woolley, B and Xia, G}, title = {Acceleration of electrons in the plasma wakefield of a proton bunch.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {363-367}, doi = {10.1038/s41586-018-0485-4}, pmid = {30188496}, issn = {1476-4687}, abstract = {High-energy particle accelerators have been crucial in providing a deeper understanding of fundamental particles and the forces that govern their interactions. To increase the energy of the particles or to reduce the size of the accelerator, new acceleration schemes need to be developed. Plasma wakefield acceleration1-5, in which the electrons in a plasma are excited, leading to strong electric fields (so called 'wakefields'), is one such promising acceleration technique. Experiments have shown that an intense laser pulse6-9 or electron bunch10,11 traversing a plasma can drive electric fields of tens of gigavolts per metre and above-well beyond those achieved in conventional radio-frequency accelerators (about 0.1 gigavolt per metre). However, the low stored energy of laser pulses and electron bunches means that multiple acceleration stages are needed to reach very high particle energies5,12. The use of proton bunches is compelling because they have the potential to drive wakefields and to accelerate electrons to high energy in a single acceleration stage13. Long, thin proton bunches can be used because they undergo a process called self-modulation14-16, a particle-plasma interaction that splits the bunch longitudinally into a series of high-density microbunches, which then act resonantly to create large wakefields. The Advanced Wakefield (AWAKE) experiment at CERN17-19 uses high-intensity proton bunches-in which each proton has an energy of 400 gigaelectronvolts, resulting in a total bunch energy of 19 kilojoules-to drive a wakefield in a ten-metre-long plasma. Electron bunches are then injected into this wakefield. Here we present measurements of electrons accelerated up to two gigaelectronvolts at the AWAKE experiment, in a demonstration of proton-driven plasma wakefield acceleration. Measurements were conducted under various plasma conditions and the acceleration was found to be consistent and reliable. The potential for this scheme to produce very high-energy electron bunches in a single accelerating stage20 means that our results are an important step towards the development of future high-energy particle accelerators21,22.}, } @article {pmid30188004, year = {2018}, author = {Fernández-Pascual, E and Mattana, E and Pritchard, HW}, title = {Seeds of future past: climate change and the thermal memory of plant reproductive traits.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12461}, pmid = {30188004}, issn = {1469-185X}, support = {Grants 'Clarín' ACA14-19 and ACB17-19//Government of Asturias and the FP7 - Marie Curie - COFUND programme of the European Commission/ ; 607785//People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme FP7/2007-2013/ ; }, abstract = {Plant persistence and migration in face of climate change depends on successful reproduction by seed, a central aspect of plant life that drives population dynamics, community assembly and species distributions. Plant reproduction by seed is a chain of physiological processes, the rates of which are a function of temperature, and can be modelled using thermal time models. Importantly, while seed reproduction responds to its instantaneous thermal environment, there is also evidence of phenotypic plasticity in response to the thermal history experienced by the plant's recent ancestors, by the reproducing plant since seedling establishment, and by its seeds both before and after their release. This phenotypic plasticity enables a thermal memory of plant reproduction, which allows individuals to acclimatise to their surroundings. This review synthesises current knowledge on the thermal memory of plant reproduction by seed, and highlights its importance for modelling approaches based on physiological thermal time. We performed a comprehensive search in the Web of Science and analysed 533 relevant articles, of which 81 provided material for a meta-analysis of thermal memory in reproductive functional traits based on the effect size Zr. The articles encompassed the topics of seed development, seed yield (mass and number), seed dormancy (physiological, morphological and physical), germination, and seedling establishment. The results of the meta-analysis provide evidence for a thermal memory of seed yield, physiological dormancy and germination. Seed mass and physiological dormancy appear to be the central hubs of this memory. We argue for integrating thermal memory into a predictive framework based on physiological time modelling. This will provide a quantitative assessment of plant reproduction, a complex system that integrates past and present thermal inputs to achieve successful reproduction in changing environments. The effects of a warming environment on plant reproduction cannot be reduced to a qualitative interpretation of absolute positives and negatives. Rather, these effects need to be understood in terms of changing rates and thresholds for the physiological process that underlie reproduction by seed.}, } @article {pmid30187979, year = {2018}, author = {Penley, MJ and Greenberg, AB and Khalid, A and Namburar, SR and Morran, LT}, title = {No measurable fitness cost to experimentally evolved host defence in the Caenorhabditis elegans-Serratia marcescens host-parasite system.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1976-1981}, doi = {10.1111/jeb.13372}, pmid = {30187979}, issn = {1420-9101}, support = {//Emory University/ ; }, abstract = {Host susceptibility to parasites can vary over space and time. Costs associated with the maintenance of host defence are thought to account for a portion of this variation. Specifically, trade-offs wherein elevated defence is maintained at the cost of fitness in the absence of the parasite may cause levels of host defence to change over time and differ between populations. In previous studies, we found that populations of the host nematode, Caenorhabditis elegans, evolved greater levels of parasite avoidance and resistance against the bacterial parasite, Serratia marcescens. Here, we passaged these host populations either in the presence or absence of the parasite to test for a cost of elevated host defences. After 16 generations, we found that elevated levels of host defence were maintained during evolution in both the presence and absence of the parasite. Further, this maintenance of defence was not the result of limited standing genetic variation, but rather the absence of a measurable cost associated with defence. Therefore, costs associated with host defence may not broadly account for differences in host susceptibility across space and time.}, } @article {pmid30187651, year = {2018}, author = {Galperin, MY}, title = {What bacteria want.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4221-4229}, doi = {10.1111/1462-2920.14398}, pmid = {30187651}, issn = {1462-2920}, support = {//NIH Intramural Research Program at the U.S. National Library of Medicine/ ; //National Institutes of Health/ ; }, abstract = {Bacterial signal transduction systems are responsible for sensing environmental cues and adjusting the cellular behaviour and/or metabolism in response to these cues. They also monitor the intracellular conditions and the status of the cell envelope and the cytoplasmic membrane and trigger various stress responses to counteract adverse changes. This surveillance involves several classes of sensor proteins: histidine kinases; chemoreceptors; membrane components of the sugar phosphotransferase system; adenylate, diadenylate and diguanylate cyclases and certain cAMP, c-di-AMP and c-di-GMP phosphodiesterases; extracytoplasmic function sigma factors and Ser/Thr/Tyr protein kinases and phosphoprotein phosphatases. We have compiled a detailed listing of sensor proteins that are encoded in the genomes of Escherichia coli, Bacillus subtilis and 10 widespread pathogens: Chlamydia trachomatis, Haemophilus influenzae, Helicobacter pylori, Mycobacterium tuberculosis, Mycoplasma pneumoniae, Neisseria gonorrhoeae, Porphyromonas gingivalis, Rickettsia typhi, Streptococcus pyogenes and Treponema pallidum, and checked what, if anything, is known about their functions. This listing shows significant gaps in the understanding of which environmental and intracellular cues are perceived by these bacteria and which cellular responses are triggered by the changes in the respective parameters. A better understanding of bacterial preferences may suggest new ways to modulate the expression of virulence factors and therefore decrease the reliance on antibiotics to fight infection.}, } @article {pmid30187633, year = {2018}, author = {Chahlafi, Z and Alvarez, L and Cava, F and Berenguer, J}, title = {The role of conserved proteins DrpA and DrpB in nitrate respiration of Thermus thermophilus.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3851-3861}, pmid = {30187633}, issn = {1462-2920}, support = {685474//H2020 European Research Council/ ; BIO2016-77031-R//Spanish Ministry of Economy and Competitiveness/ ; //Fundación Ramón Areces/ ; }, abstract = {In many Thermus thermophilus strains, nitrate respiration is encoded in mobile genetic regions, along with regulatory circuits that modulate its expression based on anoxia and nitrate presence. The oxygen-responsive system has been identified as the product of the dnrST (dnr) operon located immediately upstream of the nar operon (narCGHJIKT), which encodes the nitrate reductase (NR) and nitrate/nitrite transporters. In contrast, the nature of the nitrate sensory system is not known. Here, we analyse the putative nitrate-sensing role of the bicistronic drp operon (drpAB) present downstream of the nar operon in most denitrifying Thermus spp. Expression of drp was found to depend on the master regulator DnrT, whereas the absence of DrpA or DrpB increased the expression of both DnrS and DnrT and, concomitantly, of the NR. Absence of both proteins made expression from the dnr and nar operons independent of nitrate. Polyclonal antisera allowed us to identify DrpA as a periplasmic protein and DrpB as a membrane protein, with capacity to bind to the cytoplasmic membrane. Here, we propose a role for DrpA/DrpB as nitrate sensors during denitrification.}, } @article {pmid30187625, year = {2018}, author = {Hernández-Ruiz, M and Barber-Lluch, E and Prieto, A and Álvarez-Salgado, XA and Logares, R and Teira, E}, title = {Seasonal succession of small planktonic eukaryotes inhabiting surface waters of a coastal upwelling system.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2955-2973}, doi = {10.1111/1462-2920.14313}, pmid = {30187625}, issn = {1462-2920}, support = {CTM2014-59031-P//Spanish Ministry of Economy/ ; EM2013/023//Spanish Ministry of Economy/ ; }, abstract = {Small eukaryotes (0.2-20 μm cell-size) represent a significant fraction of the microbial plankton community in shelf waters of NW-Spain. The community composition of small eukaryotes living at the surface and at the base of the photic zone was analysed by means of 18S rDNA high-throughput sequencing on a circa-monthly basis over a 23 months period. Ostreococcus was the most abundant taxon in surface waters, showing marked peaks in read abundance in spring and late summer, while Syndiniales dominated at the base of the photic zone. A well-defined seasonal pattern of community composition, linked to the succession of the dominant taxa, was found in surface waters. Seasonality was less apparent at the base of the euphotic zone. Temporal changes in abiotic factors significantly correlated with changes in community composition in surface (r = 0.71) and at the base of the photic zone (r = 0.38). Changes in community composition significantly correlated with changes in community function-related variables (including biomass, primary production and respiration) only in surface water (r = 0.36). Co-occurrence network analyses revealed 45 significant interspecies associations among the 50 most abundant taxa with highly connected OTUs belonging to cryptophyceans. The network topology, with small-world characteristics, suggests a stabilizing role of biotic interactions to environmental disturbance.}, } @article {pmid30187624, year = {2018}, author = {Liu, S and Du, MZ and Wen, QF and Kang, J and Dong, C and Xiong, L and Huang, J and Guo, FB}, title = {Comprehensive exploration of the enzymes catalysing oxygen-involved reactions and COGs relevant to bacterial oxygen utilization.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3836-3850}, doi = {10.1111/1462-2920.14399}, pmid = {30187624}, issn = {1462-2920}, support = {31871335//National Natural Science Foundation of China/ ; ZYGX2016J117//Fundamental Research Funds for the Central Universities of China/ ; ZYGX2015Z006//Fundamental Research Funds for the Central Universities of China/ ; //Science Strength Promotion Programme of UESTC/ ; }, abstract = {To better understand the mechanisms of bacterial adaptation in oxygen environments, we explored the aerobic living-associated genes in bacteria by comparing Clusters of Orthologous Groups of proteins' (COGs) frequencies and gene expression analyses and 38 COGs were detected at significantly higher frequencies (p-value less than 1e-6) in aerobes than in anaerobes. Differential expression analyses between two conditions further narrowed the prediction to 27 aerobe-specific COGs. Then, we annotated the enzymes associated with these COGs. Literature review revealed that 14 COGs contained enzymes catalysing oxygen-involved reactions or products involved in aerobic pathways, suggesting their important roles for survival in aerobic environments. Additionally, protein-protein interaction analyses and step length comparisons of metabolic networks suggested that the other 13 COGs may function relevantly with the 14 enzymes-corresponding COGs, indicating that these genes may be highly associated with oxygen utilization. Phylogenetic and evolutionary analyses showed that the 27 COGs did not have similar trees, and all suffered purifying selection pressures. The divergent times of species containing or lacking aerobic COGs validated that the appearing time of oxygen-utilizing gene was approximately 2.80 Gyr ago. In addition to help better understand oxygen adaption, our method may be extended to identify genes relevant to other living environments.}, } @article {pmid30187462, year = {2018}, author = {Ng, J and Freitas, LB and Smith, SD}, title = {Stepwise evolution of floral pigmentation predicted by biochemical pathway structure.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {12}, pages = {2792-2802}, doi = {10.1111/evo.13589}, pmid = {30187462}, issn = {1558-5646}, support = {1413855//Division of Environmental Biology/ ; 1553114//Division of Environmental Biology/ ; }, abstract = {Developmental pathways play a major role in influencing the distribution of naturally occurring phenotypes. For example, pathway structure and regulation could make some phenotypes inaccessible or restrict the routes through which phenotypes evolve. In this study, we examine floral anthocyanin pigments across the Solanaceae family and test whether patterns of phenotypic variation are consistent with predicted constraints based on the structure of the flavonoid biosynthetic pathway. We find that anthocyanin evolution occurs in a stepwise manner whereby transitions between the production of red mono hydroxylated pelargonidin pigments and blue trihydroxylated delphinidin pigments first passes through an intermediate step of producing purple dihydroxylated cyanidin pigments. Although the transitions between these three pigment types differ in frequency, we infer that these shifts are often reversible, suggesting that the functionality of the underlying biochemical pathway is generally conserved. Furthermore, our study finds that some pigment combinations are never observed, pointing to additional constraints on naturally occurring phenotypes. Overall, our findings provide insights into how the structure of an angiosperm-wide biochemical pathway has shaped macroevolutionary variation in floral pigmentation.}, } @article {pmid30187458, year = {2018}, author = {Ershova, N}, title = {Digest: Ecological crossover effects on sexual selection.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2244-2245}, doi = {10.1111/evo.13588}, pmid = {30187458}, issn = {1558-5646}, abstract = {Environmental conditions during birds' nonbreeding season can affect the manifestation of secondary sexual traits and therefore sexual selection. In pied flycatchers, the size of the wing patch is a secondary sexual trait that signals mate value and is influenced by the previous winter's conditions. Female preference changes accordingly with the conditions of the previous nonbreeding season.}, } @article {pmid30185971, year = {2018}, author = {}, title = {Devastating museum fire, silent Mars rover and financial disclosures.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {10-11}, doi = {10.1038/d41586-018-06168-9}, pmid = {30185971}, issn = {1476-4687}, } @article {pmid30185970, year = {2018}, author = {Baker, SC}, title = {Failsafes.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {144}, doi = {10.1038/d41586-018-06089-7}, pmid = {30185970}, issn = {1476-4687}, } @article {pmid30185969, year = {2018}, author = {Holmes, D}, title = {Retinal repair: visions of the future.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {S1}, doi = {10.1038/d41586-018-06110-z}, pmid = {30185969}, issn = {1476-4687}, mesh = {Humans ; Macular Degeneration ; *Retina ; *Retinal Degeneration ; Stem Cells ; }, } @article {pmid30185968, year = {2018}, author = {Holmes, D}, title = {Reconstructing the retina.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {S2-S3}, doi = {10.1038/d41586-018-06111-y}, pmid = {30185968}, issn = {1476-4687}, } @article {pmid30185967, year = {2018}, author = {Witze, A}, title = {The quest to conquer Earth's space junk problem.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {24-26}, doi = {10.1038/d41586-018-06170-1}, pmid = {30185967}, issn = {1476-4687}, } @article {pmid30185966, year = {2018}, author = {Casacuberta, JM and Puigdomènech, P}, title = {European politicians must put greater trust in plant scientists.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {33}, doi = {10.1038/d41586-018-06129-2}, pmid = {30185966}, issn = {1476-4687}, mesh = {*Clustered Regularly Interspaced Short Palindromic Repeats ; *European Union ; Plants, Genetically Modified ; Trust ; }, } @article {pmid30185965, year = {2018}, author = {Rozell, DJ}, title = {Gerrymandering: computers are impervious to power, users are not.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {33}, doi = {10.1038/d41586-018-06127-4}, pmid = {30185965}, issn = {1476-4687}, mesh = {Algorithms ; *Computers ; *Politics ; Societies ; }, } @article {pmid30185964, year = {2018}, author = {Naylor, GJP}, title = {New York shark bites: DNA result should calm the waters.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {33}, doi = {10.1038/d41586-018-06125-6}, pmid = {30185964}, issn = {1476-4687}, } @article {pmid30185963, year = {2018}, author = {Stirling, A and Mitchell, C}, title = {Evaluate power and bias in synthesizing evidence for policy.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {33}, doi = {10.1038/d41586-018-06128-3}, pmid = {30185963}, issn = {1476-4687}, mesh = {*Bias ; Health Policy ; *Policy ; Policy Making ; }, } @article {pmid30185962, year = {2018}, author = {Aly, M}, title = {The key to a happy lab life is in the manual.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {7}, doi = {10.1038/d41586-018-06167-w}, pmid = {30185962}, issn = {1476-4687}, mesh = {Happiness ; Humans ; *Job Satisfaction ; *Laboratories ; Mental Health ; Research Personnel/*psychology ; Work-Life Balance ; Workforce ; }, } @article {pmid30185960, year = {2018}, author = {Lundblad, N}, title = {Designer atom arrays for quantum computing.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {43-44}, doi = {10.1038/d41586-018-06107-8}, pmid = {30185960}, issn = {1476-4687}, mesh = {*Quantum Theory ; }, } @article {pmid30185959, year = {2018}, author = {Jones, C}, title = {Jupiter's magnetic field revealed by the Juno spacecraft.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {36-37}, doi = {10.1038/d41586-018-06095-9}, pmid = {30185959}, issn = {1476-4687}, mesh = {Extraterrestrial Environment ; *Jupiter ; Magnetic Fields ; *Spacecraft ; }, } @article {pmid30185958, year = {2018}, author = {Partridge, L and Deelen, J and Slagboom, PE}, title = {Facing up to the global challenges of ageing.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {45-56}, doi = {10.1038/s41586-018-0457-8}, pmid = {30185958}, issn = {1476-4687}, abstract = {Longer human lives have led to a global burden of late-life disease. However, some older people experience little ill health, a trait that should be extended to the general population. Interventions into lifestyle, including increased exercise and reduction in food intake and obesity, can help to maintain healthspan. Altered gut microbiota, removal of senescent cells, blood factors obtained from young individuals and drugs can all improve late-life health in animals. Application to humans will require better biomarkers of disease risk and responses to interventions, closer alignment of work in animals and humans, and increased use of electronic health records, biobank resources and cohort studies.}, } @article {pmid30185957, year = {2018}, author = {Moore, KM and Yadav, RK and Kulowski, L and Cao, H and Bloxham, J and Connerney, JEP and Kotsiaros, S and Jørgensen, JL and Merayo, JMG and Stevenson, DJ and Bolton, SJ and Levin, SM}, title = {A complex dynamo inferred from the hemispheric dichotomy of Jupiter's magnetic field.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {76-78}, doi = {10.1038/s41586-018-0468-5}, pmid = {30185957}, issn = {1476-4687}, abstract = {The Juno spacecraft, which is in a polar orbit around Jupiter, is providing direct measurements of the planet's magnetic field close to its surface1. A recent analysis of observations of Jupiter's magnetic field from eight (of the first nine) Juno orbits has provided a spherical-harmonic reference model (JRM09)2 of Jupiter's magnetic field outside the planet. This model is of particular interest for understanding processes in Jupiter's magnetosphere, but to study the field within the planet and thus the dynamo mechanism that is responsible for generating Jupiter's main magnetic field, alternative models are preferred. Here we report maps of the magnetic field at a range of depths within Jupiter. We find that Jupiter's magnetic field is different from all other known planetary magnetic fields. Within Jupiter, most of the flux emerges from the dynamo region in a narrow band in the northern hemisphere, some of which returns through an intense, isolated flux patch near the equator. Elsewhere, the field is much weaker. The non-dipolar part of the field is confined almost entirely to the northern hemisphere, so there the field is strongly non-dipolar and in the southern hemisphere it is predominantly dipolar. We suggest that Jupiter's dynamo, unlike Earth's, does not operate in a thick, homogeneous shell, and we propose that this unexpected field morphology arises from radial variations, possibly including layering, in density or electrical conductivity, or both.}, } @article {pmid30185956, year = {2018}, author = {Kumar, A and Wu, TY and Giraldo, F and Weiss, DS}, title = {Sorting ultracold atoms in a three-dimensional optical lattice in a realization of Maxwell's demon.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {83-87}, doi = {10.1038/s41586-018-0458-7}, pmid = {30185956}, issn = {1476-4687}, abstract = {In 1872, Maxwell proposed his famous 'demon' thought experiment1. By discerning which particles in a gas are hot and which are cold, and then performing a series of reversible actions, Maxwell's demon could rearrange the particles into a manifestly lower-entropy state. This apparent violation of the second law of thermodynamics was resolved by twentieth-century theoretical work2: the entropy of the Universe is often increased while gathering information3, and there is an unavoidable entropy increase associated with the demon's memory4. The appeal of the thought experiment has led many real experiments to be framed as demon-like. However, past experiments had no intermediate information storage5, yielded only a small change in the system entropy6,7 or involved systems of four or fewer particles8-10. Here we present an experiment that captures the full essence of Maxwell's thought experiment. We start with a randomly half-filled three-dimensional optical lattice with about 60 atoms. We make the atoms sufficiently vibrationally cold so that the initial disorder is the dominant entropy. After determining where the atoms are, we execute a series of reversible operations to create a fully filled sublattice, which is a manifestly low-entropy state. Our sorting process lowers the total entropy of the system by a factor of 2.44. This highly filled ultracold array could be used as the starting point for a neutral-atom quantum computer.}, } @article {pmid30185955, year = {2018}, author = {Barredo, D and Lienhard, V and de Léséleuc, S and Lahaye, T and Browaeys, A}, title = {Synthetic three-dimensional atomic structures assembled atom by atom.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {79-82}, doi = {10.1038/s41586-018-0450-2}, pmid = {30185955}, issn = {1476-4687}, abstract = {A great challenge in current quantum science and technology research is to realize artificial systems of a large number of individually controlled quantum bits for applications in quantum computing and quantum simulation. Many experimental platforms are being explored, including solid-state systems, such as superconducting circuits1 or quantum dots2, and atomic, molecular and optical systems, such as photons, trapped ions or neutral atoms3-7. The latter offer inherently identical qubits that are well decoupled from the environment and could provide synthetic structures scalable to hundreds of qubits or more8. Quantum-gas microscopes9 allow the realization of two-dimensional regular lattices of hundreds of atoms, and large, fully loaded arrays of about 50 microtraps (or 'optical tweezers') with individual control are already available in one10 and two11 dimensions. Ultimately, however, accessing the third dimension while keeping single-atom control will be required, both for scaling to large numbers and for extending the range of models amenable to quantum simulation. Here we report the assembly of defect-free, arbitrarily shaped three-dimensional arrays, containing up to 72 single atoms. We use holographic methods and fast, programmable moving tweezers to arrange-atom by atom and plane by plane-initially disordered arrays into target structures of almost any geometry. These results present the prospect of quantum simulation with tens of qubits arbitrarily arranged in space and show that realizing systems of hundreds of individually controlled qubits is within reach using current technology.}, } @article {pmid30185954, year = {2018}, author = {Hirmas, DR and Giménez, D and Nemes, A and Kerry, R and Brunsell, NA and Wilson, CJ}, title = {Climate-induced changes in continental-scale soil macroporosity may intensify water cycle.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {100-103}, doi = {10.1038/s41586-018-0463-x}, pmid = {30185954}, issn = {1476-4687}, abstract = {Soil macroporosity affects field-scale water-cycle processes, such as infiltration, nutrient transport and runoff1,2, that are important for the development of successful global strategies that address challenges of food security, water scarcity, human health and loss of biodiversity3. Macropores-large pores that freely drain water under the influence of gravity-often represent less than 1 per cent of the soil volume, but can contribute more than 70 per cent of the total soil water infiltration4, which greatly magnifies their influence on the regional and global water cycle. Although climate influences the development of macropores through soil-forming processes, the extent and rate of such development and its effect on the water cycle are currently unknown. Here we show that drier climates induce the formation of greater soil macroporosity than do more humid ones, and that such climate-induced changes occur over shorter timescales than have previously been considered-probably years to decades. Furthermore, we find that changes in the effective porosity, a proxy for macroporosity, predicted from mean annual precipitation at the end of the century would result in changes in saturated soil hydraulic conductivity ranging from -55 to 34 per cent for five physiographic regions in the USA. Our results indicate that soil macroporosity may be altered rapidly in response to climate change and that associated continental-scale changes in soil hydraulic properties may set up unexplored feedbacks between climate and the land surface and thus intensify the water cycle.}, } @article {pmid30185910, year = {2018}, author = {Lee-Six, H and Øbro, NF and Shepherd, MS and Grossmann, S and Dawson, K and Belmonte, M and Osborne, RJ and Huntly, BJP and Martincorena, I and Anderson, E and O'Neill, L and Stratton, MR and Laurenti, E and Green, AR and Kent, DG and Campbell, PJ}, title = {Population dynamics of normal human blood inferred from somatic mutations.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {473-478}, pmid = {30185910}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Haematopoietic stem cells drive blood production, but their population size and lifetime dynamics have not been quantified directly in humans. Here we identified 129,582 spontaneous, genome-wide somatic mutations in 140 single-cell-derived haematopoietic stem and progenitor colonies from a healthy 59-year-old man and applied population-genetics approaches to reconstruct clonal dynamics. Cell divisions from early embryogenesis were evident in the phylogenetic tree; all blood cells were derived from a common ancestor that preceded gastrulation. The size of the stem cell population grew steadily in early life, reaching a stable plateau by adolescence. We estimate the numbers of haematopoietic stem cells that are actively making white blood cells at any one time to be in the range of 50,000-200,000. We observed adult haematopoietic stem cell clones that generate multilineage outputs, including granulocytes and B lymphocytes. Harnessing naturally occurring mutations to report the clonal architecture of an organ enables the high-resolution reconstruction of somatic cell dynamics in humans.}, } @article {pmid30185909, year = {2018}, author = {Kurita, M and Araoka, T and Hishida, T and O'Keefe, DD and Takahashi, Y and Sakamoto, A and Sakurai, M and Suzuki, K and Wu, J and Yamamoto, M and Hernandez-Benitez, R and Ocampo, A and Reddy, P and Shokhirev, MN and Magistretti, P and Núñez Delicado, E and Eto, H and Harii, K and Izpisua Belmonte, JC}, title = {In vivo reprogramming of wound-resident cells generates skin epithelial tissue.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {243-247}, doi = {10.1038/s41586-018-0477-4}, pmid = {30185909}, issn = {1476-4687}, support = {P30 014195/CN/NCI NIH HHS/United States ; }, abstract = {Large cutaneous ulcers are, in severe cases, life threatening1,2. As the global population ages, non-healing ulcers are becoming increasingly common1,2. Treatment currently requires the transplantation of pre-existing epithelial components, such as skin grafts, or therapy using cultured cells2. Here we develop alternative supplies of epidermal coverage for the treatment of these kinds of wounds. We generated expandable epithelial tissues using in vivo reprogramming of wound-resident mesenchymal cells. Transduction of four transcription factors that specify the skin-cell lineage enabled efficient and rapid de novo epithelialization from the surface of cutaneous ulcers in mice. Our findings may provide a new therapeutic avenue for treating skin wounds and could be extended to other disease situations in which tissue homeostasis and repair are impaired.}, } @article {pmid30185908, year = {2018}, author = {Chou, KS and Blumoff, JZ and Wang, CS and Reinhold, PC and Axline, CJ and Gao, YY and Frunzio, L and Devoret, MH and Jiang, L and Schoelkopf, RJ}, title = {Deterministic teleportation of a quantum gate between two logical qubits.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {368-373}, doi = {10.1038/s41586-018-0470-y}, pmid = {30185908}, issn = {1476-4687}, support = {DGE-1122492//National Science Foundation/International ; }, abstract = {A quantum computer has the potential to efficiently solve problems that are intractable for classical computers. However, constructing a large-scale quantum processor is challenging because of the errors and noise that are inherent in real-world quantum systems. One approach to addressing this challenge is to utilize modularity-a strategy used frequently in nature and engineering to build complex systems robustly. Such an approach manages complexity and uncertainty by assembling small, specialized components into a larger architecture. These considerations have motivated the development of a quantum modular architecture, in which separate quantum systems are connected into a quantum network via communication channels1,2. In this architecture, an essential tool for universal quantum computation is the teleportation of an entangling quantum gate3-5, but such teleportation has hitherto not been realized as a deterministic operation. Here we experimentally demonstrate the teleportation of a controlled-NOT (CNOT) gate, which we make deterministic by using real-time adaptive control. In addition, we take a crucial step towards implementing robust, error-correctable modules by enacting the gate between two logical qubits, encoding quantum information redundantly in the states of superconducting cavities6. By using such an error-correctable encoding, our teleported gate achieves a process fidelity of 79 per cent. Teleported gates have implications for fault-tolerant quantum computation3, and when realized within a network can have broad applications in quantum communication, metrology and simulations1,2,7. Our results illustrate a compelling approach for implementing multi-qubit operations on logical qubits and, if integrated with quantum error-correction protocols, indicate a promising path towards fault-tolerant quantum computation using a modular architecture.}, } @article {pmid30185907, year = {2018}, author = {Mongera, A and Rowghanian, P and Gustafson, HJ and Shelton, E and Kealhofer, DA and Carn, EK and Serwane, F and Lucio, AA and Giammona, J and Campàs, O}, title = {A fluid-to-solid jamming transition underlies vertebrate body axis elongation.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {401-405}, pmid = {30185907}, issn = {1476-4687}, support = {R01 HD095797/HD/NICHD NIH HHS/United States ; R21 HD084285/HD/NICHD NIH HHS/United States ; CMMI-1562910//National Science Foundation/International ; }, abstract = {Just as in clay moulding or glass blowing, physically sculpting biological structures requires the constituent material to locally flow like a fluid while maintaining overall mechanical integrity like a solid. Disordered soft materials, such as foams, emulsions and colloidal suspensions, switch from fluid-like to solid-like behaviours at a jamming transition1-4. Similarly, cell collectives have been shown to display glassy dynamics in 2D and 3D5,6 and jamming in cultured epithelial monolayers7,8, behaviours recently predicted theoretically9-11 and proposed to influence asthma pathobiology8 and tumour progression12. However, little is known about whether these seemingly universal behaviours occur in vivo13 and, specifically, whether they play any functional part during embryonic morphogenesis. Here, by combining direct in vivo measurements of tissue mechanics with analysis of cellular dynamics, we show that during vertebrate body axis elongation, posterior tissues undergo a jamming transition from a fluid-like behaviour at the extending end, the mesodermal progenitor zone, to a solid-like behaviour in the presomitic mesoderm. We uncover an anteroposterior, N-cadherin-dependent gradient in yield stress that provides increasing mechanical integrity to the presomitic mesoderm, consistent with the tissue transiting from a wetter to a dryer foam-like architecture. Our results show that cell-scale stresses fluctuate rapidly (within about 1 min), enabling cell rearrangements and effectively 'melting' the tissue at the growing end. Persistent (more than 0.5 h) stresses at supracellular scales, rather than cell-scale stresses, guide morphogenetic flows in fluid-like tissue regions. Unidirectional axis extension is sustained by the reported rigidification of the presomitic mesoderm, which mechanically supports posterior, fluid-like tissues during remodelling before their maturation. The spatiotemporal control of fluid-like and solid-like tissue states may represent a generic physical mechanism of embryonic morphogenesis.}, } @article {pmid30185906, year = {2018}, author = {Brick, K and Thibault-Sennett, S and Smagulova, F and Lam, KG and Pu, Y and Pratto, F and Camerini-Otero, RD and Petukhova, GV}, title = {Extensive sex differences at the initiation of genetic recombination.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {338-342}, doi = {10.1038/s41586-018-0492-5}, pmid = {30185906}, issn = {1476-4687}, support = {R01 GM084104/GM/NIGMS NIH HHS/United States ; }, abstract = {Meiotic recombination differs between males and females; however, when and how these differences are established is unknown. Here we identify extensive sex differences at the initiation of recombination by mapping hotspots of meiotic DNA double-strand breaks in male and female mice. Contrary to past findings in humans, few hotspots are used uniquely in either sex. Instead, grossly different recombination landscapes result from up to fifteen-fold differences in hotspot usage between males and females. Indeed, most recombination occurs at sex-biased hotspots. Sex-biased hotspots seem to be partly determined by chromosome structure, and DNA methylation, which is absent in females at the onset of meiosis, has a substantial role. Sex differences are also evident later in meiosis as the rate at which meiotic breaks are repaired as crossovers differs between males and females in distal regions. The suppression of distal crossovers may help to minimize age-related aneuploidy that arises owing to cohesion loss during dictyate arrest in females.}, } @article {pmid30185905, year = {2018}, author = {Samaha, H and Pignata, A and Fousek, K and Ren, J and Lam, FW and Stossi, F and Dubrulle, J and Salsman, VS and Krishnan, S and Hong, SH and Baker, ML and Shree, A and Gad, AZ and Shum, T and Fukumura, D and Byrd, TT and Mukherjee, M and Marrelli, SP and Orange, JS and Joseph, SK and Sorensen, PH and Taylor, MD and Hegde, M and Mamonkin, M and Jain, RK and El-Naggar, S and Ahmed, N}, title = {A homing system targets therapeutic T cells to brain cancer.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {331-337}, doi = {10.1038/s41586-018-0499-y}, pmid = {30185905}, issn = {1476-4687}, support = {K08 GM123261/GM/NIGMS NIH HHS/United States ; T32 HL092332/HL/NHLBI NIH HHS/United States ; R01 AI067946/AI/NIAID NIH HHS/United States ; R35 CA197743/CA/NCI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P01 CA080124/CA/NCI NIH HHS/United States ; }, abstract = {Successful T cell immunotherapy for brain cancer requires that the T cells can access tumour tissues, but this has been difficult to achieve. Here we show that, in contrast to inflammatory brain diseases such as multiple sclerosis, where endothelial cells upregulate ICAM1 and VCAM1 to guide the extravasation of pro-inflammatory cells, cancer endothelium downregulates these molecules to evade immune recognition. By contrast, we found that cancer endothelium upregulates activated leukocyte cell adhesion molecule (ALCAM), which allowed us to overcome this immune-evasion mechanism by creating an ALCAM-restricted homing system (HS). We re-engineered the natural ligand of ALCAM, CD6, in a manner that triggers initial anchorage of T cells to ALCAM and conditionally mediates a secondary wave of adhesion by sensitizing T cells to low-level ICAM1 on the cancer endothelium, thereby creating the adhesion forces necessary to capture T cells from the bloodstream. Cytotoxic HS T cells robustly infiltrated brain cancers after intravenous injection and exhibited potent antitumour activity. We have therefore developed a molecule that targets the delivery of T cells to brain cancer.}, } @article {pmid30185904, year = {2018}, author = {Mooley, KP and Deller, AT and Gottlieb, O and Nakar, E and Hallinan, G and Bourke, S and Frail, DA and Horesh, A and Corsi, A and Hotokezaka, K}, title = {Superluminal motion of a relativistic jet in the neutron-star merger GW170817.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {355-359}, doi = {10.1038/s41586-018-0486-3}, pmid = {30185904}, issn = {1476-4687}, abstract = {The binary neutron-star merger GW1708171 was accompanied by radiation across the electromagnetic spectrum2 and localized2 to the galaxy NGC 4993 at a distance3 of about 41 megaparsecs from Earth. The radio and X-ray afterglows of GW170817 exhibited delayed onset4-7, a gradual increase8 in the emission with time (proportional to t0.8) to a peak about 150 days after the merger event9, followed by a relatively rapid decline9,10. So far, various models have been proposed to explain the afterglow emission, including a choked-jet cocoon4,8,11-13 and a successful-jet cocoon4,8,11-18 (also called a structured jet). However, the observational data have remained inconclusive10,15,19,20 as to whether GW170817 launched a successful relativistic jet. Here we report radio observations using very long-baseline interferometry. We find that the compact radio source associated with GW170817 exhibits superluminal apparent motion between 75 days and 230 days after the merger event. This measurement breaks the degeneracy between the choked- and successful-jet cocoon models and indicates that, although the early-time radio emission was powered by a wide-angle outflow8 (a cocoon), the late-time emission was most probably dominated by an energetic and narrowly collimated jet (with an opening angle of less than five degrees) and observed from a viewing angle of about 20 degrees. The imaging of a collimated relativistic outflow emerging from GW170817 adds substantial weight to the evidence linking binary neutron-star mergers and short γ-ray bursts.}, } @article {pmid30185903, year = {2018}, author = {Ikebuchi, Y and Aoki, S and Honma, M and Hayashi, M and Sugamori, Y and Khan, M and Kariya, Y and Kato, G and Tabata, Y and Penninger, JM and Udagawa, N and Aoki, K and Suzuki, H}, title = {Coupling of bone resorption and formation by RANKL reverse signalling.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {195-200}, doi = {10.1038/s41586-018-0482-7}, pmid = {30185903}, issn = {1476-4687}, abstract = {Receptor activator of nuclear factor-kappa B (RANK) ligand (RANKL) binds RANK on the surface of osteoclast precursors to trigger osteoclastogenesis. Recent studies have indicated that osteocytic RANKL has an important role in osteoclastogenesis during bone remodelling; however, the role of osteoblastic RANKL remains unclear. Here we show that vesicular RANK, which is secreted from the maturing osteoclasts, binds osteoblastic RANKL and promotes bone formation by triggering RANKL reverse signalling, which activates Runt-related transcription factor 2 (Runx2). The proline-rich motif in the RANKL cytoplasmic tail is required for reverse signalling, and a RANKL(Pro29Ala) point mutation reduces activation of the reverse signalling pathway. The coupling of bone resorption and formation is disrupted in RANKL(Pro29Ala) mutant mice, indicating that osteoblastic RANKL functions as a coupling signal acceptor that recognizes vesicular RANK. RANKL reverse signalling is therefore a potential pharmacological target for avoiding the reduced bone formation associated with inhibition of osteoclastogenesis.}, } @article {pmid30185564, year = {2018}, author = {Cumming, GS and von Cramon-Taubadel, S}, title = {Linking economic growth pathways and environmental sustainability by understanding development as alternate social-ecological regimes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9533-9538}, pmid = {30185564}, issn = {1091-6490}, abstract = {Scientists understand how global ecological degradation is occurring but not why it seems to be so difficult to reverse. We used national-level data and a mathematical model to provide an empirical test of the hypothesis that national economies display two distinct economic regimes that are maintained by self-reinforcing feedbacks between natural resources and society. Our results not only support previous findings that two distinct groups exist, but also show that countries move toward one of these two different equilibrium points because of their different patterns of natural resource use and responses to population growth. At the less economically developed equilibrium point maintained by "green-loop" feedbacks, human populations depend more directly on ecosystems for income. At the more economically developed equilibrium point maintained by "red-loop" feedbacks, nonecosystem services (e.g., technology, manufacturing, services) generate the majority of national gross domestic product (GDP), but increasing consumption of natural resources means that environmental impacts are higher and are often exported (via cross-scale feedbacks) to other countries. Feedbacks between income and population growth are pushing countries farther from sustainability. Our analysis shows that economic growth alone cannot lead to environmental sustainability and that current trajectories of resource use cannot be sustained without breaking feedback loops in national and international economies.}, } @article {pmid30185563, year = {2018}, author = {Kojima, Y and Soetedjo, R}, title = {Elimination of the error signal in the superior colliculus impairs saccade motor learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8987-E8995}, pmid = {30185563}, issn = {1091-6490}, support = {P30 EY001730/EY/NEI NIH HHS/United States ; P51 OD010425/OD/NIH HHS/United States ; R01 EY019258/EY/NEI NIH HHS/United States ; R01 EY023277/EY/NEI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/drug effects/physiology ; Animals ; Cerebellum/*physiology ; Electrodes ; Eye Movement Measurements ; Learning/*physiology ; Macaca mulatta ; Male ; Muscimol/pharmacology ; Psychomotor Performance/drug effects/*physiology ; Reward ; Saccades/drug effects/*physiology ; Superior Colliculi/*physiology ; }, abstract = {When movements become dysmetric, the resultant motor error induces a plastic change in the cerebellum to correct the movement, i.e., motor adaptation. Current evidence suggests that the error signal to the cerebellum is delivered by complex spikes originating in the inferior olive (IO). To prove a causal link between the IO error signal and motor adaptation, several studies blocked the IO, which, unfortunately, affected not only the adaptation but also the movement itself. We avoided this confound by inactivating the source of an error signal to the IO. Several studies implicate the superior colliculus (SC) as the source of the error signal to the IO for saccade adaptation. When we inactivated the SC, the metrics of the saccade to be adapted were unchanged, but saccade adaptation was impaired. Thus, an intact rostral SC is necessary for saccade adaptation. Our data provide experimental evidence for the cerebellar learning theory that requires an error signal to drive motor adaptation.}, } @article {pmid30185562, year = {2018}, author = {Eggersdorfer, ML and Seybold, H and Ofner, A and Weitz, DA and Studart, AR}, title = {Wetting controls of droplet formation in step emulsification.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9479-9484}, pmid = {30185562}, issn = {1091-6490}, support = {R01 EB023287/EB/NIBIB NIH HHS/United States ; }, mesh = {Algorithms ; Computer Simulation ; Emulsions/*chemistry ; *Models, Theoretical ; Particle Size ; *Physical Phenomena ; Surface Properties ; Thermodynamics ; *Wettability ; }, abstract = {The formation of droplets is ubiquitous in many natural and industrial processes and has reached an unprecedented level of control with the emergence of milli- and microfluidics. Although important insight into the mechanisms of droplet formation has been gained over the past decades, a sound understanding of the physics underlying this phenomenon and the effect of the fluid's flow and wetting properties on the droplet size and production rate is still missing, especially for the widely applied method of step emulsification. In this work, we elucidate the physical controls of microdroplet formation in step emulsification by using the wetting of fluidic channels as a tunable parameter to explore a broad set of emulsification conditions. With the help of high-speed measurements, we unequivocally show that the final droplet pinch-off is triggered by a Rayleigh-Plateau-type instability. The droplet size, however, is not determined by the Rayleigh-Plateau breakup, but by the initial wetting regime, where the fluid's contact angle plays a crucial role. We develop a physical theory for the wetting process, which closely describes our experimental measurements without invoking any free fit parameter. Our theory predicts the initiation of the Rayleigh-Plateau breakup and the transition from dripping to jetting as a function of the fluid's contact angle. Additionally, the theory solves the conundrum why there is a minimal contact angle of α = 2π/3 = 120° for which droplets can form.}, } @article {pmid30185561, year = {2018}, author = {Chowdhury, S and Otomo, C and Leitner, A and Ohashi, K and Aebersold, R and Lander, GC and Otomo, T}, title = {Insights into autophagosome biogenesis from structural and biochemical analyses of the ATG2A-WIPI4 complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {42}, pages = {E9792-E9801}, pmid = {30185561}, issn = {1091-6490}, support = {DP2 EB020402/EB/NIBIB NIH HHS/United States ; R01 GM092740/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Autophagosomes/*metabolism ; *Autophagy ; Autophagy-Related Proteins/chemistry/*metabolism ; Endoplasmic Reticulum/*metabolism ; Humans ; Membrane Proteins/chemistry/*metabolism ; Multiprotein Complexes/chemistry/*metabolism ; Phosphatidylinositol Phosphates/chemistry/*metabolism ; Protein Conformation ; Sequence Homology ; }, abstract = {Autophagy is an enigmatic cellular process in which double-membrane compartments, called "autophagosomes, form de novo adjacent to the endoplasmic reticulum (ER) and package cytoplasmic contents for delivery to lysosomes. Expansion of the precursor membrane phagophore requires autophagy-related 2 (ATG2), which localizes to the PI3P-enriched ER-phagophore junction. We combined single-particle electron microscopy, chemical cross-linking coupled with mass spectrometry, and biochemical analyses to characterize human ATG2A in complex with the PI3P effector WIPI4. ATG2A is a rod-shaped protein that can bridge neighboring vesicles through interactions at each of its tips. WIPI4 binds to one of the tips, enabling the ATG2A-WIPI4 complex to tether a PI3P-containing vesicle to another PI3P-free vesicle. These data suggest that the ATG2A-WIPI4 complex mediates ER-phagophore association and/or tethers vesicles to the ER-phagophore junction, establishing the required organization for phagophore expansion via the transfer of lipid membranes from the ER and/or the vesicles to the phagophore.}, } @article {pmid30185560, year = {2018}, author = {Beaupere, C and Dinatto, L and Wasko, BM and Chen, RB and VanValkenburg, L and Kiflezghi, MG and Lee, MB and Promislow, DEL and Dang, W and Kaeberlein, M and Labunskyy, VM}, title = {Genetic screen identifies adaptive aneuploidy as a key mediator of ER stress resistance in yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9586-9591}, pmid = {30185560}, issn = {1091-6490}, support = {R00 AG040191/AG/NIA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R56 AG054566/AG/NIA NIH HHS/United States ; K99 AG040191/AG/NIA NIH HHS/United States ; R01 AG056359/AG/NIA NIH HHS/United States ; P30 AG013280/AG/NIA NIH HHS/United States ; R01 AG049494/AG/NIA NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; *Aneuploidy ; Chromosomes, Fungal/genetics ; Drug Resistance, Fungal/genetics ; Endoplasmic Reticulum Stress/*genetics ; Gene Expression Regulation, Fungal/*physiology ; Phosphotransferases (Phosphate Group Acceptor)/genetics/metabolism ; Proteasome Endopeptidase Complex/genetics/metabolism ; Protein Folding ; Saccharomyces cerevisiae/*physiology ; Tunicamycin/pharmacology ; Unfolded Protein Response/physiology ; }, abstract = {The yeast genome becomes unstable during stress, which often results in adaptive aneuploidy, allowing rapid activation of protective mechanisms that restore cellular homeostasis. In this study, we performed a genetic screen in Saccharomyces cerevisiae to identify genome adaptations that confer resistance to tunicamycin-induced endoplasmic reticulum (ER) stress. Whole-genome sequencing of tunicamycin-resistant mutants revealed that ER stress resistance correlated significantly with gains of chromosomes II and XIII. We found that chromosome duplications allow adaptation of yeast cells to ER stress independently of the unfolded protein response, and that the gain of an extra copy of chromosome II alone is sufficient to induce protection from tunicamycin. Moreover, the protective effect of disomic chromosomes can be recapitulated by overexpression of several genes located on chromosome II. Among these genes, overexpression of UDP-N-acetylglucosamine-1-P transferase (ALG7), a subunit of the 20S proteasome (PRE7), and YBR085C-A induced tunicamycin resistance in wild-type cells, whereas deletion of all three genes completely reversed the tunicamycin-resistance phenotype. Together, our data demonstrate that aneuploidy plays a critical role in adaptation to ER stress by increasing the copy number of ER stress protective genes. While aneuploidy itself leads to proteotoxic stress, the gene-specific effects of chromosome II aneuploidy counteract the negative effect resulting in improved protein folding.}, } @article {pmid30185559, year = {2018}, author = {Kunduri, G and Turner-Evans, D and Konya, Y and Izumi, Y and Nagashima, K and Lockett, S and Holthuis, J and Bamba, T and Acharya, U and Acharya, JK}, title = {Defective cortex glia plasma membrane structure underlies light-induced epilepsy in cpes mutants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8919-E8928}, pmid = {30185559}, issn = {1091-6490}, support = {R01 GM110288/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Cell Membrane/enzymology ; Cerebral Cortex/cytology/*enzymology ; Disease Models, Animal ; Drosophila Proteins/*genetics ; Drosophila melanogaster ; Epilepsy, Reflex/*genetics ; Humans ; Male ; Membrane Proteins/*genetics ; Mutation ; Nerve Tissue Proteins/*genetics ; Neuroglia/cytology/*enzymology ; Neurons/cytology/enzymology ; Sphingomyelins/metabolism ; Transferases (Other Substituted Phosphate Groups)/*genetics ; }, abstract = {Seizures induced by visual stimulation (photosensitive epilepsy; PSE) represent a common type of epilepsy in humans, but the molecular mechanisms and genetic drivers underlying PSE remain unknown, and no good genetic animal models have been identified as yet. Here, we show an animal model of PSE, in Drosophila, owing to defective cortex glia. The cortex glial membranes are severely compromised in ceramide phosphoethanolamine synthase (cpes)-null mutants and fail to encapsulate the neuronal cell bodies in the Drosophila neuronal cortex. Expression of human sphingomyelin synthase 1, which synthesizes the closely related ceramide phosphocholine (sphingomyelin), rescues the cortex glial abnormalities and PSE, underscoring the evolutionarily conserved role of these lipids in glial membranes. Further, we show the compromise in plasma membrane structure that underlies the glial cell membrane collapse in cpes mutants and leads to the PSE phenotype.}, } @article {pmid30185558, year = {2018}, author = {Kaplan, E and Zubedat, S and Radzishevsky, I and Valenta, AC and Rechnitz, O and Sason, H and Sajrawi, C and Bodner, O and Konno, K and Esaki, K and Derdikman, D and Yoshikawa, T and Watanabe, M and Kennedy, RT and Billard, JM and Avital, A and Wolosker, H}, title = {ASCT1 (Slc1a4) transporter is a physiologic regulator of brain d-serine and neurodevelopment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9628-9633}, pmid = {30185558}, issn = {1091-6490}, mesh = {Amino Acid Transport System ASC/genetics/*metabolism ; Animals ; Astrocytes/physiology ; Brain/cytology/diagnostic imaging/embryology/*physiology ; Cell Communication/*physiology ; Disease Models, Animal ; Glycine/metabolism ; HEK293 Cells ; Humans ; Long-Term Potentiation/physiology ; Magnetic Resonance Imaging ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microcephaly/diagnostic imaging/*genetics/metabolism/pathology ; Minor Histocompatibility Antigens/genetics/metabolism ; Neurons/physiology ; Primary Cell Culture ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Serine/*metabolism ; Synaptic Transmission/physiology ; }, abstract = {d-serine is a physiologic coagonist of NMDA receptors, but little is known about the regulation of its synthesis and synaptic turnover. The amino acid exchangers ASCT1 (Slc1a4) and ASCT2 (Slc1a5) are candidates for regulating d-serine levels. Using ASCT1 and ASCT2 KO mice, we report that ASCT1, rather than ASCT2, is a physiologic regulator of d-serine metabolism. ASCT1 is a major d-serine uptake system in astrocytes and can also export l-serine via heteroexchange, supplying neurons with the substrate for d-serine synthesis. ASCT1-KO mice display lower levels of brain d-serine along with higher levels of l-alanine, l-threonine, and glycine. Deletion of ASCT1 was associated with neurodevelopmental alterations including lower hippocampal and striatal volumes and changes in the expression of neurodevelopmental-relevant genes. Furthermore, ASCT1-KO mice exhibited deficits in motor function, spatial learning, and affective behavior, along with changes in the relative contributions of d-serine vs. glycine in mediating NMDA receptor activity. In vivo microdialysis demonstrated lower levels of extracellular d-serine in ASCT1-KO mice, confirming altered d-serine metabolism. These alterations are reminiscent of some of the neurodevelopmental phenotypes exhibited by patients with ASCT1 mutations. ASCT1-KO mice provide a useful model for potential therapeutic interventions aimed at correcting the metabolic impairments in patients with ASCT1 mutations.}, } @article {pmid30185557, year = {2018}, author = {Liao, Z and Gauquelin, N and Green, RJ and Müller-Caspary, K and Lobato, I and Li, L and Van Aert, S and Verbeeck, J and Huijben, M and Grisolia, MN and Rouco, V and El Hage, R and Villegas, JE and Mercy, A and Bibes, M and Ghosez, P and Sawatzky, GA and Rijnders, G and Koster, G}, title = {Metal-insulator-transition engineering by modulation tilt-control in perovskite nickelates for room temperature optical switching.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9515-9520}, pmid = {30185557}, issn = {1091-6490}, support = {//CIHR/Canada ; }, abstract = {In transition metal perovskites ABO3, the physical properties are largely driven by the rotations of the BO6 octahedra, which can be tuned in thin films through strain and dimensionality control. However, both approaches have fundamental and practical limitations due to discrete and indirect variations in bond angles, bond lengths, and film symmetry by using commercially available substrates. Here, we introduce modulation tilt control as an approach to tune the ground state of perovskite oxide thin films by acting explicitly on the oxygen octahedra rotation modes-that is, directly on the bond angles. By intercalating the prototype SmNiO3 target material with a tilt-control layer, we cause the system to change the natural amplitude of a given rotation mode without affecting the interactions. In contrast to strain and dimensionality engineering, our method enables a continuous fine-tuning of the materials' properties. This is achieved through two independent adjustable parameters: the nature of the tilt-control material (through its symmetry, elastic constants, and oxygen rotation angles), and the relative thicknesses of the target and tilt-control materials. As a result, a magnetic and electronic phase diagram can be obtained, normally only accessible by A-site element substitution, within the single SmNiO3 compound. With this unique approach, we successfully adjusted the metal-insulator transition (MIT) to room temperature to fulfill the desired conditions for optical switching applications.}, } @article {pmid30185556, year = {2018}, author = {Jones, BR and Kinloch, NN and Horacsek, J and Ganase, B and Harris, M and Harrigan, PR and Jones, RB and Brockman, MA and Joy, JB and Poon, AFY and Brumme, ZL}, title = {Phylogenetic approach to recover integration dates of latent HIV sequences within-host.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8958-E8967}, pmid = {30185556}, issn = {1091-6490}, support = {FRN-130609//CIHR/Canada ; PJT-155990//CIHR/Canada ; PJT-153391//CIHR/Canada ; HIG-133050//CIHR/Canada ; PJT-148621//CIHR/Canada ; UM1 AI126617/AI/NIAID NIH HHS/United States ; }, mesh = {Datasets as Topic ; HIV Infections/blood/*genetics/virology ; HIV-1/*genetics/isolation & purification ; Host-Pathogen Interactions/*genetics ; Humans ; Models, Genetic ; *Phylogeny ; Proviruses/genetics/isolation & purification ; RNA, Viral/genetics/isolation & purification ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Time Factors ; Viremia/blood/genetics/virology ; Virus Integration/genetics ; Virus Latency/*genetics ; }, abstract = {Given that HIV evolution and latent reservoir establishment occur continually within-host, and that latently infected cells can persist long-term, the HIV reservoir should comprise a genetically heterogeneous archive recapitulating within-host HIV evolution. However, this has yet to be conclusively demonstrated, in part due to the challenges of reconstructing within-host reservoir establishment dynamics over long timescales. We developed a phylogenetic framework to reconstruct the integration dates of individual latent HIV lineages. The framework first involves inference and rooting of a maximum-likelihood phylogeny relating plasma HIV RNA sequences serially sampled before the initiation of suppressive antiretroviral therapy, along with putative latent sequences sampled thereafter. A linear model relating root-to-tip distances of plasma HIV RNA sequences to their sampling dates is used to convert root-to-tip distances of putative latent lineages to their establishment (integration) dates. Reconstruction of the ages of putative latent sequences sampled from chronically HIV-infected individuals up to 10 y following initiation of suppressive therapy revealed a genetically heterogeneous reservoir that recapitulated HIV's within-host evolutionary history. Reservoir sequences were interspersed throughout multiple within-host lineages, with the oldest dating to >20 y before sampling; historic genetic bottleneck events were also recorded therein. Notably, plasma HIV RNA sequences isolated from a viremia blip in an individual receiving otherwise suppressive therapy were highly genetically diverse and spanned a 20-y age range, suggestive of spontaneous in vivo HIV reactivation from a large latently infected cell pool. Our framework for reservoir dating provides a potentially powerful addition to the HIV persistence research toolkit.}, } @article {pmid30185555, year = {2018}, author = {Wall, RJ and Rico, E and Lukac, I and Zuccotto, F and Elg, S and Gilbert, IH and Freund, Y and Alley, MRK and Field, MC and Wyllie, S and Horn, D}, title = {Clinical and veterinary trypanocidal benzoxaboroles target CPSF3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9616-9621}, pmid = {30185555}, issn = {1091-6490}, support = {105021/Z/14/Z//Wellcome Trust/United Kingdom ; MR/K008749/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; 100320/Z/12/Z//Wellcome Trust/United Kingdom ; 203134/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Benzamides/pharmacology/therapeutic use ; Boron Compounds/pharmacology/therapeutic use ; CRISPR-Cas Systems ; Cell Nucleus/genetics/metabolism ; Cleavage And Polyadenylation Specificity Factor/*antagonists & inhibitors/genetics/metabolism ; Drug Resistance/drug effects/genetics ; Gene Knockdown Techniques ; Gene Library ; High-Throughput Screening Assays/methods ; Humans ; Molecular Docking Simulation ; Protozoan Proteins/*antagonists & inhibitors/genetics/metabolism ; RNA Processing, Post-Transcriptional/drug effects ; RNA, Messenger/metabolism ; RNA, Protozoan/metabolism ; Trypanocidal Agents/*pharmacology/therapeutic use ; Trypanosoma brucei brucei/drug effects/*physiology ; Trypanosomiasis, African/*prevention & control/transmission/veterinary ; Valine/analogs & derivatives/pharmacology/therapeutic use ; }, abstract = {African trypanosomes cause lethal and neglected tropical diseases, known as sleeping sickness in humans and nagana in animals. Current therapies are limited, but fortunately, promising therapies are in advanced clinical and veterinary development, including acoziborole (AN5568 or SCYX-7158) and AN11736, respectively. These benzoxaboroles will likely be key to the World Health Organization's target of disease control by 2030. Their mode of action was previously unknown. We have developed a high-coverage overexpression library and use it here to explore drug mode of action in Trypanosoma brucei Initially, an inhibitor with a known target was used to select for drug resistance and to test massive parallel library screening and genome-wide mapping; this effectively identified the known target and validated the approach. Subsequently, the overexpression screening approach was used to identify the target of the benzoxaboroles, Cleavage and Polyadenylation Specificity Factor 3 (CPSF3, Tb927.4.1340). We validated the CPSF3 endonuclease as the target, using independent overexpression strains. Knockdown provided genetic validation of CPSF3 as essential, and GFP tagging confirmed the expected nuclear localization. Molecular docking and CRISPR-Cas9-based editing demonstrated how acoziborole can specifically block the active site and mRNA processing by parasite, but not host CPSF3. Thus, our findings provide both genetic and chemical validation for CPSF3 as an important drug target in trypanosomes and reveal inhibition of mRNA maturation as the mode of action of the trypanocidal benzoxaboroles. Understanding the mechanism of action of benzoxaborole-based therapies can assist development of improved therapies, as well as the prediction and monitoring of resistance, if or when it arises.}, } @article {pmid30185554, year = {2018}, author = {Fu, Q and Shaik, MM and Cai, Y and Ghantous, F and Piai, A and Peng, H and Rits-Volloch, S and Liu, Z and Harrison, SC and Seaman, MS and Chen, B and Chou, JJ}, title = {Structure of the membrane proximal external region of HIV-1 envelope glycoprotein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8892-E8899}, pmid = {30185554}, issn = {1091-6490}, support = {UM1 AI100645/AI/NIAID NIH HHS/United States ; P41 EB002026/EB/NIBIB NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 AI127193/AI/NIAID NIH HHS/United States ; R56 AI129721/AI/NIAID NIH HHS/United States ; R01 AI106488/AI/NIAID NIH HHS/United States ; }, mesh = {HIV Antigens/*chemistry/immunology ; HIV-1/*chemistry/immunology ; Immunoglobulin Fab Fragments/immunology ; Lipid Bilayers/chemistry ; Magnetic Resonance Spectroscopy ; Membrane Fusion ; Protein Domains ; Virion/*chemistry/immunology ; env Gene Products, Human Immunodeficiency Virus/*chemistry ; }, abstract = {The membrane-proximal external region (MPER) of the HIV-1 envelope glycoprotein (Env) bears epitopes of broadly neutralizing antibodies (bnAbs) from infected individuals; it is thus a potential vaccine target. We report an NMR structure of the MPER and its adjacent transmembrane domain in bicelles that mimic a lipid-bilayer membrane. The MPER lies largely outside the lipid bilayer. It folds into a threefold cluster, stabilized mainly by conserved hydrophobic residues and potentially by interaction with phospholipid headgroups. Antigenic analysis and comparison with published images from electron cryotomography of HIV-1 Env on the virion surface suggest that the structure may represent a prefusion conformation of the MPER, distinct from the fusion-intermediate state targeted by several well-studied bnAbs. Very slow bnAb binding indicates that infrequent fluctuations of the MPER structure give these antibodies occasional access to alternative conformations of MPER epitopes. Mutations in the MPER not only impede membrane fusion but also influence presentation of bnAb epitopes in other regions. These results suggest strategies for developing MPER-based vaccine candidates.}, } @article {pmid30185553, year = {2018}, author = {Lee, KS and Huh, S and Lee, S and Wu, Z and Kim, AK and Kang, HY and Lu, B}, title = {Altered ER-mitochondria contact impacts mitochondria calcium homeostasis and contributes to neurodegeneration in vivo in disease models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8844-E8853}, pmid = {30185553}, issn = {1091-6490}, support = {R01 MH080378/MH/NIMH NIH HHS/United States ; R01 NS084412/NS/NINDS NIH HHS/United States ; R01 NS083417/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Calcium/*metabolism ; Chelating Agents/pharmacology ; Disease Models, Animal ; Dopaminergic Neurons/cytology/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/*metabolism ; Endoplasmic Reticulum/drug effects/*metabolism ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics/metabolism ; Loss of Function Mutation ; Mitochondria/drug effects/*metabolism ; Parkinson Disease/*pathology ; Protein-Serine-Threonine Kinases/genetics/metabolism ; rho GTP-Binding Proteins/metabolism ; }, abstract = {Calcium (Ca2+) homeostasis is essential for neuronal function and survival. Altered Ca2+ homeostasis has been consistently observed in neurological diseases. How Ca2+ homeostasis is achieved in various cellular compartments of disease-relevant cell types is not well understood. Here we show in Drosophila Parkinson's disease (PD) models that Ca2+ transport from the endoplasmic reticulum (ER) to mitochondria through the ER-mitochondria contact site (ERMCS) critically regulates mitochondrial Ca2+ (mito-Ca2+) homeostasis in dopaminergic (DA) neurons, and that the PD-associated PINK1 protein modulates this process. In PINK1 mutant DA neurons, the ERMCS is strengthened and mito-Ca2+ level is elevated, resulting in mitochondrial enlargement and neuronal death. Miro, a well-characterized component of the mitochondrial trafficking machinery, mediates the effects of PINK1 on mito-Ca2+ and mitochondrial morphology, apparently in a transport-independent manner. Miro overexpression mimics PINK1 loss-of-function effect, whereas inhibition of Miro or components of the ERMCS, or pharmacological modulation of ERMCS function, rescued PINK1 mutant phenotypes. Mito-Ca2+ homeostasis is also altered in the LRRK2-G2019S model of PD and the PAR-1/MARK model of neurodegeneration, and genetic or pharmacological restoration of mito-Ca2+ level is beneficial in these models. Our results highlight the importance of mito-Ca2+ homeostasis maintained by Miro and the ERMCS to mitochondrial physiology and neuronal integrity. Targeting this mito-Ca2+ homeostasis pathway holds promise for a therapeutic strategy for neurodegenerative diseases.}, } @article {pmid30185233, year = {2018}, author = {Mukherjee, C and Beall, CJ and Griffen, AL and Leys, EJ}, title = {High-resolution ISR amplicon sequencing reveals personalized oral microbiome.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {153}, pmid = {30185233}, issn = {2049-2618}, support = {R01 DE024327/DE/NIDCR NIH HHS/United States ; R01 DE024463/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Sequencing of the 16S rRNA gene has been the standard for studying the composition of microbial communities. While it allows identification of bacteria at the level of species, this method does not usually provide sufficient information to resolve communities at the sub-species level. Species-level resolution is not adequate for studies of transmission or stability or for exploring subspecies variation in disease association. Strain level analysis using whole metagenome shotgun sequencing has significant limitations that can make it unsuitable for large-scale studies. Achieving sufficient depth of sequencing can be cost-prohibitive, and even with adequate coverage, deconvoluting complex communities such as the oral microbiota is computationally very challenging. Thus, there is a need for high-resolution, yet cost-effective, high-throughput methods for characterizing microbial communities.

RESULTS: Significant improvement in resolution for amplicon-based bacterial community analysis was achieved by combining amplicon sequencing of a high-diversity marker gene, the ribosomal 16-23S intergenic spacer region (ISR), with a probabilistic error modeling based denoising algorithm, DADA2. The resolving power of this new approach was compared to that of both standard and high-resolution 16S-based approaches using a set of longitudinal subgingival plaque samples. The ISR strategy resulted in a 5.2-fold increase in community resolution compared to reference-based 16S rRNA gene analysis and showed 100% accuracy in predicting the correct source of a clinical sample. Individuals' microbial communities were highly personalized, and although they exhibited some drift in membership and levels over time, that difference was always smaller than the differences between any two subjects, even after 1 year. The construction of an ISR database from publicly available genomic sequences allowed us to explore genomic variation within species, resulting in the identification of multiple variants of the ISR for most species.

CONCLUSIONS: The ISR approach resulted in significantly improved resolution of communities and revealed a highly personalized human oral microbiota that was stable over 1 year. Multiple ISR types were observed for all species examined, demonstrating a high level of subspecies variation in the oral microbiota. The approach is high-throughput, high-resolution yet cost-effective, allowing subspecies-level community fingerprinting at a cost comparable to that of 16S rRNA gene amplicon sequencing. It will be useful for a range of applications that require high-resolution identification of organisms, including microbial tracking, community fingerprinting, and potentially for identification of virulence-associated strains.}, } @article {pmid30185229, year = {2018}, author = {Böhning, D and Böhning, W and Guha, N and Cowan, DA and Bartlett, C and Sönksen, PH and Holt, RIG}, title = {A correction to the age-adjustment of the GH-2000 score used in the detection of growth hormone misuse.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {650}, pmid = {30185229}, issn = {1756-0500}, mesh = {*Doping in Sports ; Female ; Growth Hormone/analysis/*therapeutic use ; Human Growth Hormone/*analysis ; Humans ; Insulin-Like Growth Factor I/analysis ; Male ; Procollagen ; Reference Values ; *Substance Abuse Detection ; }, abstract = {OBJECTIVE: The GH-2000 biomarker test has been introduced by the World Anti-Doping Agency as a method of detecting growth hormone misuse in professional sport. The test involves the measurement insulin-like growth factor-I and the amino-terminal pro-peptide of type III collagen (P-III-NP) which increase in a dose-dependent manner in response to GH. These measurements are combined in sex specific formulae that include an age adjustment. The original age adjustment overcorrects the effect of age in male athletes and could potentially place older men at a disadvantage. The purpose of this note is to investigate the performance of a previously suggested correction term in two new and larger data sets.

RESULTS: The GH-2000 score was calculated for 7307 samples obtained from 15 accredited WADA laboratories in 2017 and 3916 samples measured at Drug Control Centre, King's College London, UK between 2013 and 2017. The GH-2000 scores were investigated for positive age effects using standard regression modelling. As previously, all analyses confirmed a positive age effect. Applying the earlier suggested correction term of 0.032 × age showed a significant over-correction leading to a negative association of the GH-2000 score with age. We now suggest a smaller age correction of 0.020 × age, which corresponds to the smallest effect found in the earlier studies.}, } @article {pmid30185226, year = {2018}, author = {Chang, HW and Yan, D and Singh, R and Liu, J and Lu, X and Ucmak, D and Lee, K and Afifi, L and Fadrosh, D and Leech, J and Vasquez, KS and Lowe, MM and Rosenblum, MD and Scharschmidt, TC and Lynch, SV and Liao, W}, title = {Alteration of the cutaneous microbiome in psoriasis and potential role in Th17 polarization.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {154}, pmid = {30185226}, issn = {2049-2618}, support = {U01 AI119125/AI/NIAID NIH HHS/United States ; R01 AR065174/AR/NIAMS NIH HHS/United States ; DP2 AR068130/AR/NIAMS NIH HHS/United States ; K08 AR068409/AR/NIAMS NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Psoriasis impacts 1-3% of the world's population and is characterized by hyper-proliferation of keratinocytes and increased inflammation. At the molecular level, psoriasis is commonly driven by a Th17 response, which serves as a major therapeutic target. Microbiome perturbations have been associated with several immune-mediated diseases such as atopic dermatitis, asthma, and multiple sclerosis. Although a few studies have investigated the association between the skin microbiome and psoriasis, conflicting results have been reported plausibly due to the lack of standardized sampling and profiling protocols, or to inherent microbial variability across human subjects and underpowered studies. To better understand the link between the cutaneous microbiota and psoriasis, we conducted an analysis of skin bacterial communities of 28 psoriasis patients and 26 healthy subjects, sampled at six body sites using a standardized protocol and higher sequencing depth compared to previous studies. Mouse studies were employed to examine dermal microbial-immune interactions of bacterial species identified from our study.

RESULTS: Skin microbiome profiling based on sequencing the 16S rRNA V1-V3 variable region revealed significant differences between the psoriasis-associated and healthy skin microbiota. Comparing the overall community structures, psoriasis-associated microbiota displayed higher diversity and more heterogeneity compared to healthy skin bacterial communities. Specific microbial signatures were associated with psoriatic lesional, psoriatic non-lesional, and healthy skin. Specifically, relative enrichment of Staphylococcus aureus was strongly associated with both lesional and non-lesional psoriatic skin. In contrast, Staphylococcus epidermidis and Propionibacterium acnes were underrepresented in psoriatic lesions compared to healthy skin, especially on the arm, gluteal fold, and trunk. Employing a mouse model to further study the impact of cutaneous Staphylcoccus species on the skin T cell differentiation, we found that newborn mice colonized with Staphylococcus aureus demonstrated strong Th17 polarization, whereas mice colonized with Staphylococcus epidermidis or un-colonized controls showed no such response.

CONCLUSION: Our results suggest that microbial communities on psoriatic skin is substantially different from those on healthy skin. The psoriatic skin microbiome has increased diversity and reduced stability compared to the healthy skin microbiome. The loss of community stability and decrease in immunoregulatory bacteria such as Staphylococcus epidermidis and Propionibacterium acnes may lead to higher colonization with pathogens such as Staphylococcus aureus, which could exacerbate cutaneous inflammation along the Th17 axis.}, } @article {pmid30185210, year = {2018}, author = {Marron, EM and Viejo-Sobera, R and Quintana, M and Redolar-Ripoll, D and Rodríguez, D and Garolera, M}, title = {Transcranial magnetic stimulation intervention in Alzheimer's disease: a research proposal for a randomized controlled trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {648}, pmid = {30185210}, issn = {1756-0500}, mesh = {Alzheimer Disease/*therapy ; Double-Blind Method ; Humans ; Prefrontal Cortex ; Quality of Life ; *Randomized Controlled Trials as Topic ; *Transcranial Magnetic Stimulation ; Treatment Outcome ; }, abstract = {OBJECTIVE: Alzheimer's disease is a major health problem in our society. To date, pharmacological treatments have obtained poor results and there is a growing interest in finding non-pharmacological interventions for this disease. Transcranial magnetic stimulation (TMS) is a non-invasive technique that is able to induce changes in brain activity and long-term modifications in impaired neural networks, becoming a promising clinical intervention. Our goal is to study the benefit of individualized TMS targeting based on the patient's functional connectivity (personalized targeting), and short duration TMS protocol, instead of current non-individualized and longer session approaches. A double blind randomized controlled trial will be conducted to assess the effects of TMS treatment immediately, 1 month, 3 months and 6 months after the end of the intervention. Fifty-four patients with a diagnosis of Alzheimer's disease will be randomly allocated into experimental (active TMS), sham control, or conventional intervention control group. We will quantify changes in cognitive, functional, and emotional deficits in Alzheimer patients, as well as the functional connectivity changes induced by the TMS treatment.

RESULTS: We expect to demonstrate that personalized TMS intervention has a measurable positive impact in cognition, emotion, daily living activities and brain connectivity, thus representing a potential treatment for Alzheimer's disease. Trial registration The trial has been prospectively registered at ClinicalTrials.gov, identifier NCT03121066. Date of registration: 04/19/2017.}, } @article {pmid30185209, year = {2018}, author = {Ielapi, A and Vasiliauskaite, E and Hendrickx, M and Forward, M and Lammens, N and Van Paepegem, W and Deckers, JP and Vermandel, M and De Beule, M}, title = {A novel experimental setup for evaluating the stiffness of ankle foot orthoses.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {649}, pmid = {30185209}, issn = {1756-0500}, support = {140164//VLAIO & A_STREAM_AFO project/ ; 140165//VLAIO & A_STREAM_AFO project/ ; }, mesh = {*Ankle ; Ankle Joint ; Belgium ; Biomechanical Phenomena ; Equipment Design ; Female ; Foot ; *Foot Orthoses ; Gait ; Humans ; Male ; Orthotic Devices ; *Range of Motion, Articular ; Reproducibility of Results ; }, abstract = {OBJECTIVE: The purpose of this study was the construction of a new semi-automated experimental setup for the evaluation of the stiffness of ankle foot orthoses (AFOs) around an axis aligned to the anatomical ankle joint during the second rocker of the gait. The setup, developed in close collaboration with the orthopedic device company V!GO NV (Wetteren, Belgium), allows measurement of plantarflexion and dorsiflexion in the sagittal plane for a maximal range of motion of 50° (- 25° plantarflexion up to 25° dorsiflexion) in a non-destructive way.

RESULTS: The mechanical properties of four 3D printed AFOs are investigated, based on the ranges of motion derived from the gait assessment of the patients when they walked with their AFO. The reliability of the stiffness measures was studied by the evaluation of the test-retest repeatability and the intra-tester and inter-tester variability. These studies revealed that the ankle stiffness can be measured with high reliability (ICC = 0.94-1.00). The obtained outcomes indicate that the experimental setup could be applied to measure the ankle stiffness of any topology of AFOs and, in the future, help finding the correlation with the information coming from the gait assessment of the patients.}, } @article {pmid30185166, year = {2018}, author = {Liechti, N and Schürch, N and Bruggmann, R and Wittwer, M}, title = {The genome of Naegleria lovaniensis, the basis for a comparative approach to unravel pathogenicity factors of the human pathogenic amoeba N. fowleri.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {654}, pmid = {30185166}, issn = {1471-2164}, mesh = {Amoeba/*microbiology ; Genomics/*methods ; Humans ; Molecular Sequence Annotation ; Multigene Family/genetics ; Naegleria/*genetics/*physiology ; Phylogeny ; Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: Members of the genus Naegleria are free-living eukaryotes with the capability to transform from the amoeboid form into resting cysts or moving flagellates in response to environmental conditions. More than 40 species have been characterized, but only Naegleria fowleri (N. fowleri) is known as a human pathogen causing primary amoebic meningoencephalitis (PAM), a fast progressing and mostly fatal disease of the central nervous system. Several studies report an involvement of phospholipases and other molecular factors, but the mechanisms involved in pathogenesis are still poorly understood. To gain a better understanding of the relationships within the genus of Naegleria and to investigate pathogenicity factors of N. fowleri, we characterized the genome of its closest non-pathogenic relative N. lovaniensis.

RESULTS: To gain insights into the taxonomy of Naegleria, we sequenced the genome of N. lovaniensis using long read sequencing technology. The assembly of the data resulted in a 30 Mb genome including the circular mitochondrial sequence. Unravelling the phylogenetic relationship using OrthoMCL protein clustering and maximum likelihood methods confirms the close relationship of N. lovaniensis and N. fowleri. To achieve an overview of the diversity of Naegleria proteins and to assess characteristics of the human pathogen N. fowleri, OrthoMCL protein clustering including data of N. fowleri, N. lovaniensis and N. gruberi was performed. GO enrichment analysis shows an association of N. fowleri specific proteins to the GO terms "Membrane" and "Protein Secretion."

CONCLUSION: In this study, we characterize the hitherto unknown genome of N. lovaniensis. With the description of the 30 Mb genome, a further piece is added to reveal the complex taxonomic relationship of Naegleria. Further, the whole genome sequencing data confirms the hypothesis of the close relationship between N. fowleri and N. lovaniensis. Therefore, the genome of N. lovaniensis provides the basis for further comparative approaches on the molecular and genomic level to unravel pathogenicity factors of its closest human pathogenic relative N. fowleri and possible treatment options for the rare but mostly fatal primary meningoencephalitis.}, } @article {pmid30185164, year = {2018}, author = {Hadjadj, L and Bakour, S and Rolain, JM}, title = {Co-occurrence of carbapenemase encoding genes in Acinetobacter baumannii, a dream or reality?.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {107}, pmid = {30185164}, issn = {1471-2180}, abstract = {BACKGROUND: Acinetobacter baumannii is an important opportunistic pathogen that is rapidly evolving towards multidrug resistance and is responsible for life-threatening infections. Carbapenems are commonly used to treat A. baumannii infections but the emergence of carbapenemase encoding genes, such as blaOXA-23-like, blaOXA-24-like, blaOXA-58-like, and blaNDM has been reported. Moreover, several studies have reported the co-occurrence of two distinct carbapenemases in some isolates. The aim of the present study is to demonstrate whether the phenomenon of co-occurrence of two distinct carbapenemase encoding genes in a single isolate still exists.

RESULTS: We studied six strains of A. baumannii including one harboring blaOXA-23-like and blaOXA-24-like genes and five with blaOXA-23-like and blaNDM genes. One colony of each strain was inoculated in sterile water and diluted ten-fold. Each dilution was cultivated on trypticase soy agar plates for 24 h at 37 °C and the isolated bacteria were analyzed. For two of the six tested strains, we identified two different populations of A. baumannii, each with a different carbapenemase, genes encoding aminoglycoside modifying enzymes, resistance phenotype, and clonal type. In addition, the two different populations had the same aspect on the agar plate.

CONCLUSIONS: Here, we demonstrate that A. baumannii infections could be linked to multiple clones harboring different carbapenemase encoding genes in the same sample. In addition, we describe an easy method of verifying the presence of co-occurrence of carbapenemase in one isolate.}, } @article {pmid30185158, year = {2018}, author = {Feng, JY and Li, M and Zhao, S and Zhang, C and Yang, ST and Qiao, S and Tan, WF and Qu, HJ and Wang, DY and Pu, ZG}, title = {Analysis of evolution and genetic diversity of sweetpotato and its related different polyploidy wild species I. trifida using RAD-seq.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {181}, pmid = {30185158}, issn = {1471-2229}, support = {2015JSCX-003, 2016LWJJ-002, 2016ZYPZ-005, 2017QNJJ-001 and 2017QNJJ-021//Financial Innovation Project of Sichuan Province/ ; 31101119//National Natural Science Foundation of China/ ; CARS-10-B5//the earmarked fund for China Agriculture Research System/ ; }, mesh = {DNA, Plant ; *Evolution, Molecular ; Genetic Markers ; Genetic Speciation ; *Genetic Variation ; Ipomoea/*genetics ; Ipomoea batatas/genetics ; Microsatellite Repeats ; Phylogeny ; Polymorphism, Single Nucleotide ; *Polyploidy ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Sweetpotato (Ipomoea batatas (L.) Lam.) is one of the most important crops from the family of Convolvulaceae. It is widely reported that cultivated sweetpotato was originated from Ipomoea trifida. However, diploid, tetraploid and hexaploid I. trifida were found in nature. The relationship, between them, and among them and sweetpotato, is remaining unclear.

RESULTS: In the present study, we detected the genome diversity and relationship of sweetpotato and different polyploidy types I. trifida using Restriction-site Associated DNA Sequencing (RAD-seq). A total of 38,605 RAD-tags containing 832,204 SNPs had been identified. These tags were annotated using five public databases, about 11,519 tags were aligned to functional genes in various pathways. Based on SNP genotype, phylogenetic relation analysis results confirmed that cultivated sweetpotato has a closer relationship with I. trifida 6× than with I. trifida 4X and I. trifida 2×. Besides, 5042 SSRs were detected in I. trifida 6×, and 3202 pairs of high-quality SSR primers were developed. A total of 68 primers were randomly selected and synthesized, of which 61 were successfully amplified.

CONCLUSION: These results provided new evidence that cultivated sweetpotato originated from I. trifida 6×, and that I. trifida 6× evolved from I. trifida 4X and I. trifida 2×. Therefore, using I. trifida 6× as the model plant of sweetpotato research should be more practical than using I. trifida 2× in the future. Meanwhile, sequence information and markers from the present study will be helpful for sweetpotato and I. trifida studies in the future.}, } @article {pmid30185153, year = {2018}, author = {Dergunova, LV and Filippenkov, IB and Stavchansky, VV and Denisova, AE and Yuzhakov, VV and Mozerov, SA and Gubsky, LV and Limborska, SA}, title = {Genome-wide transcriptome analysis using RNA-Seq reveals a large number of differentially expressed genes in a transient MCAO rat model.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {655}, pmid = {30185153}, issn = {1471-2164}, support = {16-14-00077//Russian Science Foundation/ ; }, mesh = {Animals ; Brain/diagnostic imaging/metabolism ; Disease Models, Animal ; *Gene Expression Profiling ; Infarction, Middle Cerebral Artery/complications/diagnostic imaging/*genetics/pathology ; Magnetic Resonance Imaging ; Rats ; Reperfusion Injury/complications ; *Sequence Analysis, RNA ; Signal Transduction/genetics ; }, abstract = {BACKGROUND: The transient middle cerebral artery occlusion (tMCAO) model is used for studying the molecular mechanisms of ischemic damage and neuroprotection. Numerous studies have demonstrated the role of individual genes and associated signaling pathways in the pathogenesis of ischemic stroke. Here, the tMCAO model was used to investigate the genome-wide response of the transcriptome of rat brain tissues to the damaging effect of ischemia and subsequent reperfusion.

RESULTS: Magnetic resonance imaging and histological examination showed that the model of focal ischemia based on endovascular occlusion of the right middle cerebral artery for 90 min using a monofilament, followed by restoration of the blood flow, led to reproducible localization of ischemic damage in the subcortical structures of the brain. High-throughput RNA sequencing (RNA-Seq) revealed the presence of differentially expressed genes (DEGs) in subcortical structures of rat brains resulting from hemisphere damage by ischemia after tMCAO, as well as in the corresponding parts of the brains of sham-operated animals. Real-time reverse transcription polymerase chain reaction expression analysis of 20 genes confirmed the RNA-Seq results. We identified 469 and 1939 genes that exhibited changes in expression of > 1.5-fold at 4.5 and 24 h after tMCAO, respectively. Interestingly, we found 2741 and 752 DEGs under ischemia-reperfusion and sham-operation conditions at 24 h vs. 4.5 h after tMCAO, respectively. The activation of a large number of genes involved in inflammatory, immune and stress responses, apoptosis, ribosome function, DNA replication and other processes was observed in ischemia-reperfusion conditions. Simultaneously, massive down-regulation of the mRNA levels of genes involved in the functioning of neurotransmitter systems was recorded. A Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis showed that dozens of signaling pathways were associated with DEGs in ischemia-reperfusion conditions.

CONCLUSIONS: The data obtained revealed a global profile of gene expression in the rat brain sub-cortex under tMCAO conditions that can be used to identify potential therapeutic targets in the development of new strategies for the prevention and treatment of ischemic stroke.}, } @article {pmid30184201, year = {2018}, author = {Rathi, S and Tak, N and Bissa, G and Chouhan, B and Ojha, A and Adhikari, D and Barik, SK and Satyawada, RR and Sprent, JI and James, EK and Gehlot, HS}, title = {Selection of Bradyrhizobium or Ensifer symbionts by the native Indian caesalpinioid legume Chamaecrista pumila depends on soil pH and other edaphic and climatic factors.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy180}, pmid = {30184201}, issn = {1574-6941}, abstract = {Nodules of Chamaecrista pumila growing in several locations in India were sampled for anatomical studies and for characterization of their rhizobial microsymbionts. Regardless of their region of origin, the nodules were indeterminate with their bacteroids contained within symbiosomes which were surrounded by pectin. More than 150 strains were isolated from alkaline soils from the Thar Desert (Rajasthan), wet-acidic soils of Shillong (Meghalaya), and from trap experiments using soils from four other states with different agro-ecological regions. Molecular phylogenetic analysis based on five housekeeping (rrs, recA, glnII, dnaK andatpD) and two symbiotic (nodA and nifH) genes was performed for selected strains. Chamaecrista pumila was shown to be nodulated by niche-specific diverse strains of either Ensifer or Bradyrhizobium in alkaline (Thar Desert) to neutral (Tamil Nadu) soils and only Bradyrhizobium strains in acidic (Shillong) soils. Concatenated core gene phylogenies showed four novel Ensifer-MLSA types and nine Bradyrhizobium-MLSA types. Genetically diverse Ensifer strains harbored similar sym genes which were novel. In contrast, significant symbiotic diversity was observed in the Bradyrhizobium strains. The C. pumila strains cross-nodulated Vigna radiata and some wild papilionoid and mimosoid legumes. It is suggested that soil pH and moisture level played important roles in structuring the C. pumila microsymbiont community.}, } @article {pmid30184140, year = {2018}, author = {Langdon, QK and Peris, D and Kyle, B and Hittinger, CT}, title = {sppIDer: A Species Identification Tool to Investigate Hybrid Genomes with High-Throughput Sequencing.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2835-2849}, pmid = {30184140}, issn = {1537-1719}, support = {T32 GM007133/GM/NIGMS NIH HHS/United States ; }, abstract = {The genomics era has expanded our knowledge about the diversity of the living world, yet harnessing high-throughput sequencing data to investigate alternative evolutionary trajectories, such as hybridization, is still challenging. Here we present sppIDer, a pipeline for the characterization of interspecies hybrids and pure species, that illuminates the complete composition of genomes. sppIDer maps short-read sequencing data to a combination genome built from reference genomes of several species of interest and assesses the genomic contribution and relative ploidy of each parental species, producing a series of colorful graphical outputs ready for publication. As a proof-of-concept, we use the genus Saccharomyces to detect and visualize both interspecies hybrids and pure strains, even with missing parental reference genomes. Through simulation, we show that sppIDer is robust to variable reference genome qualities and performs well with low-coverage data. We further demonstrate the power of this approach in plants, animals, and other fungi. sppIDer is robust to many different inputs and provides visually intuitive insight into genome composition that enables the rapid identification of species and their interspecies hybrids. sppIDer exists as a Docker image, which is a reusable, reproducible, transparent, and simple-to-run package that automates the pipeline and installation of the required dependencies (https://github.com/GLBRC/sppIDer; last accessed September 6, 2018).}, } @article {pmid30184128, year = {2018}, author = {Mangin, I and Dossou-Yovo, F and Lévêque, C and Dessoy, MV and Sawoo, O and Suau, A and Pochart, P}, title = {Oral administration of viable Bifidobacterium pseudolongum strain Patronus modified colonic microbiota and increased mucus layer thickness in rat.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy177}, pmid = {30184128}, issn = {1574-6941}, abstract = {This study aimed at evaluating the alteration of the colonic microbiota and the changes in the mucus layer thickness induced by oral administration of living bifidobacteria in rats. The study was performed on rats fed with Bifidobacterium pseudolongum strain Patronus (1010 bacteria per day for 7 days). This bacterial administration led to a large increase of mucus thickness (57%, P < 0.05). Both quantitative PCR and high-throughput sequencing of bacterial 16S rRNA gene revealed a significant increase of the amount of the Bifidobacterium genus in the microbiota of rats fed with the strain Patronus, associated with a decrease of Akkermansia muciniphila. The increase in mucus thickness could be due to an increase of the bifidobacteria per se or via the decrease of A. muciniphila, a major mucin-degrading species. As the mucus layer plays an essential role in gut protection, our data enlighten the importance of studying mucus-degrading bacteria for understanding the underlying etiology of diseases such as intestinal bowel diseases and to implement new therapeutic strategies.}, } @article {pmid30184127, year = {2018}, author = {Vacek, V and Novák, LVF and Treitli, SC and Táborský, P and Cepicka, I and Kolísko, M and Keeling, PJ and Hampl, V}, title = {Fe-S Cluster Assembly in Oxymonads and Related Protists.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2712-2718}, pmid = {30184127}, issn = {1537-1719}, abstract = {The oxymonad Monocercomonoides exilis was recently reported to be the first eukaryote that has completely lost the mitochondrial compartment. It was proposed that an important prerequisite for such a radical evolutionary step was the acquisition of the SUF Fe-S cluster assembly pathway from prokaryotes, making the mitochondrial ISC pathway dispensable. We have investigated genomic and transcriptomic data from six oxymonad species and their relatives, composing the group Preaxostyla (Metamonada, Excavata), for the presence and absence of enzymes involved in Fe-S cluster biosynthesis. None possesses enzymes of mitochondrial ISC pathway and all apparently possess the SUF pathway, composed of SufB, C, D, S, and U proteins, altogether suggesting that the transition from ISC to SUF preceded their last common ancestor. Interestingly, we observed that SufDSU were fused in all three oxymonad genomes, and in the genome of Paratrimastix pyriformis. The donor of the SUF genes is not clear from phylogenetic analyses, but the enzyme composition of the pathway and the presence of SufDSU fusion suggests Firmicutes, Thermotogae, Spirochaetes, Proteobacteria, or Chloroflexi as donors. The inventory of the downstream CIA pathway enzymes is consistent with that of closely related species that retain ISC, indicating that the switch from ISC to SUF did not markedly affect the downstream process of maturation of cytosolic and nuclear Fe-S proteins.}, } @article {pmid30184126, year = {2018}, author = {Foflonker, F and Mollegard, D and Ong, M and Yoon, HS and Bhattacharya, D}, title = {Genomic Analysis of Picochlorum Species Reveals How Microalgae May Adapt to Variable Environments.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2702-2711}, doi = {10.1093/molbev/msy167}, pmid = {30184126}, issn = {1537-1719}, abstract = {Understanding how microalgae adapt to rapidly changing environments is not only important to science but can help clarify the potential impact of climate change on the biology of primary producers. We sequenced and analyzed the nuclear genome of multiple Picochlorum isolates (Chlorophyta) to elucidate strategies of environmental adaptation. It was previously found that coordinated gene regulation is involved in adaptation to salinity stress, and here we show that gene gain and loss also play key roles in adaptation. We determined the extent of horizontal gene transfer (HGT) from prokaryotes and their role in the origin of novel functions in the Picochlorum clade. HGT is an ongoing and dynamic process in this algal clade with adaptation being driven by transfer, divergence, and loss. One HGT candidate that is differentially expressed under salinity stress is indolepyruvate decarboxylase that is involved in the production of a plant auxin that mediates bacteria-diatom symbiotic interactions. Large differences in levels of heterozygosity were found in diploid haplotypes among Picochlorum isolates. Biallelic divergence was pronounced in P. oklahomensis (salt plains environment) when compared with its closely related sister taxon Picochlorum SENEW3 (brackish water environment), suggesting a role of diverged alleles in response to environmental stress. Our results elucidate how microbial eukaryotes with limited gene inventories expand habitat range from mesophilic to halophilic through allelic diversity, and with minor but important contributions made by HGT. We also explore how the nature and quality of genome data may impact inference of nuclear ploidy.}, } @article {pmid30184119, year = {2018}, author = {Mathai, PP and Dunn, HM and Magnone, P and Brown, CM and Chun, CL and Sadowsky, MJ}, title = {Spatial and temporal characterization of epiphytic microbial communities associated with Eurasian watermilfoil: a highly invasive macrophyte in North America.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {12}, pages = {}, doi = {10.1093/femsec/fiy178}, pmid = {30184119}, issn = {1574-6941}, abstract = {Bacterial communities that inhabit the surface of aquatic plants are thought to play a critical role in relation to host fitness and function. However, little is known about their structure and dynamics in comparison with those of bacterioplankton. In this study, we performed a comprehensive spatial and temporal characterization of epibacterial communities associated with Eurasian watermilfoil (EWM; Myriophyllum spicatum), an invasive macrophyte, which has established itself in thousands of lakes across North America. EWM samples were collected from 10 lakes in Minnesota, once a month, for six consecutive months, along with surrounding water and sediment. High-throughput DNA sequencing analyses, performed on all samples (n = 522) using the Illumina platform, indicated that EWM-associated epibacterial communities were distinct from those found in water and sediment. EWM-specific microbiota was comprised of operational taxonomic units classified to the families Rhodobacteraceae, Comamonadaceae, Cyanobacteria Subsection I Family I, Aeromonadaceae, Planctomycetaceae, Sphingomonadaceae and Verrucomicrobiaceae. In addition, several identified taxa were overrepresented in EWM samples when compared to water and sediment. Amongst all the environmental factors examined, water temperature had the greatest influence on epibacterial community structure. Our findings suggest that EWM harbor specific, but temporally adapted, epibacterial communities that are potentially involved in host-microbe interactions.}, } @article {pmid30184112, year = {2018}, author = {Liu, S and Schnable, JC and Ott, A and Yeh, CE and Springer, NM and Yu, J and Muehlbauer, G and Timmermans, MCP and Scanlon, MJ and Schnable, PS}, title = {Intragenic Meiotic Crossovers Generate Novel Alleles with Transgressive Expression Levels.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2762-2772}, pmid = {30184112}, issn = {1537-1719}, abstract = {Meiotic recombination is an evolutionary force that generates new genetic diversity upon which selection can act. Whereas multiple studies have assessed genome-wide patterns of recombination and specific cases of intragenic recombination, few studies have assessed intragenic recombination genome-wide in higher eukaryotes. We identified recombination events within or near genes in a population of maize recombinant inbred lines (RILs) using RNA-sequencing data. Our results are consistent with case studies that have shown that intragenic crossovers cluster at the 5' ends of some genes. Further, we identified cases of intragenic crossovers that generate transgressive transcript accumulation patterns, that is, recombinant alleles displayed higher or lower levels of expression than did nonrecombinant alleles in any of ∼100 RILs, implicating intragenic recombination in the generation of new variants upon which selection can act. Thousands of apparent gene conversion events were identified, allowing us to estimate the genome-wide rate of gene conversion at SNP sites (4.9 × 10-5). The density of syntenic genes (i.e., those conserved at the same genomic locations since the divergence of maize and sorghum) exhibits a substantial correlation with crossover frequency, whereas the density of nonsyntenic genes (i.e., those which have transposed or been lost subsequent to the divergence of maize and sorghum) shows little correlation, suggesting that crossovers occur at higher rates in syntenic genes than in nonsyntenic genes. Increased rates of crossovers in syntenic genes could be either a consequence of the evolutionary conservation of synteny or a biological process that helps to maintain synteny.}, } @article {pmid30184103, year = {2018}, author = {Das, R and Upadhyai, P}, title = {An Ancestry Informative Marker Set Which Recapitulates the Known Fine Structure of Populations in South Asia.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2408-2416}, pmid = {30184103}, issn = {1759-6653}, abstract = {The inference of genomic ancestry using ancestry informative markers (AIMs) can be useful for a range of studies in evolutionary genetics, biomedical research, and forensic analyses. However, the determination of AIMs for highly admixed populations with complex ancestries has remained a formidable challenge. Given the immense genetic heterogeneity and unique population structure of the Indian subcontinent, here we sought to derive AIMs that would yield a cohesive and faithful understanding of South Asian genetic origins. To discern the most optimal strategy for extracting AIMs for South Asians we compared three commonly used AIMs-determining methods namely, Infocalc, FST, and Smart Principal Component Analysis with ADMIXTURE, using previously published whole genome data from the Indian subcontinent. Our findings suggest that the Infocalc approach is likely most suitable for delineation of South Asian AIMs. In particular, Infocalc-2,000 (N = 2,000) appeared as the most informative South Asian AIMs panel that recapitulated the finer structure within South Asian genomes with high degree of sensitivity and precision, whereas a negative control with an equivalent number of randomly selected markers when used to interrogate the South Asian populations, failed to do so. We discuss the utility of all approaches under evaluation for AIMs derivation and interpreting South Asian genomic ancestries. Notably, this is the first report of an AIMs panel for South Asian ancestry inference. Overall these findings may aid in developing cost-effective resources for large-scale demographic analyses and foster expansion of our knowledge of human origins and disease, in the South Asian context.}, } @article {pmid30184095, year = {2018}, author = {Liu, J and Robinson-Rechavi, M}, title = {Adaptive Evolution of Animal Proteins over Development: Support for the Darwin Selection Opportunity Hypothesis of Evo-Devo.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2862-2872}, pmid = {30184095}, issn = {1537-1719}, abstract = {A driving hypothesis of evolutionary developmental biology is that animal morphological diversity is shaped both by adaptation and by developmental constraints. Here, we have tested Darwin's "selection opportunity" hypothesis, according to which high evolutionary divergence in late development is due to strong positive selection. We contrasted it to a "developmental constraint" hypothesis, according to which late development is under relaxed negative selection. Indeed, the highest divergence between species, both at the morphological and molecular levels, is observed late in embryogenesis and postembryonically. To distinguish between adaptation and relaxation hypotheses, we investigated the evidence of positive selection on protein-coding genes in relation to their expression over development, in fly Drosophila melanogaster, zebrafish Danio rerio, and mouse Mus musculus. First, we found that genes specifically expressed in late development have stronger signals of positive selection. Second, over the full transcriptome, genes with evidence for positive selection trend to be expressed in late development. Finally, genes involved in pathways with cumulative evidence of positive selection have higher expression in late development. Overall, there is a consistent signal that positive selection mainly affects genes and pathways expressed in late embryonic development and in adult. Our results imply that the evolution of embryogenesis is mostly conservative, with most adaptive evolution affecting some stages of postembryonic gene expression, and thus postembryonic phenotypes. This is consistent with the diversity of environmental challenges to which juveniles and adults are exposed.}, } @article {pmid30184083, year = {2018}, author = {Cheng, W and Zhou, Y and Miao, X and An, C and Gao, H}, title = {The Putative Smallest Introns in the Arabidopsis Genome.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2551-2557}, pmid = {30184083}, issn = {1759-6653}, abstract = {Most eukaryotic genes contain introns, which are noncoding sequences that are removed during premRNA processing. Introns are usually preserved across evolutionary time. However, the sizes of introns vary greatly. In Arabidopsis, some introns are longer than 10 kilo base pairs (bp) and others are predicted to be shorter than 10 bp. To identify the shortest intron in the genome, we analyzed the predicted introns in annotated version 10 of the Arabidopsis thaliana genome and found 103 predicted introns that are 30 bp or shorter, which make up only 0.08% of all introns in the genome. However, our own bioinformatics and experimental analyses found no evidence for the existence of these predicted introns. The predicted introns of 30-39 bp, 40-49 bp, and 50-59 bp in length are also rare and constitute only 0.07%, 0.2%, and 0.28% of all introns in the genome, respectively. An analysis of 30 predicted introns 31-59 bp long verified two in this range, both of which were 59 bp long. Thus, this study suggests that there is a limit to how small introns in A. thaliana can be, which is useful for the understanding of the evolution and processing of small introns in plants in general.}, } @article {pmid30184074, year = {2018}, author = {Li, L and Barth, NKH and Hirth, E and Taher, L}, title = {Pairs of Adjacent Conserved Noncoding Elements Separated by Conserved Genomic Distances Act as Cis-Regulatory Units.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2535-2550}, pmid = {30184074}, issn = {1759-6653}, abstract = {Comparative genomic studies have identified thousands of conserved noncoding elements (CNEs) in the mammalian genome, many of which have been reported to exert cis-regulatory activity. We analyzed ∼5,500 pairs of adjacent CNEs in the human genome and found that despite divergence at the nucleotide sequence level, the inter-CNE distances of the pairs are under strong evolutionary constraint, with inter-CNE sequences featuring significantly lower transposon densities than expected. Further, we show that different degrees of conservation of the inter-CNE distance are associated with distinct cis-regulatory functions at the CNEs. Specifically, the CNEs in pairs with conserved and mildly contracted inter-CNE sequences are the most likely to represent active or poised enhancers. In contrast, CNEs in pairs with extremely contracted or expanded inter-CNE sequences are associated with no cis-regulatory activity. Furthermore, we observed that functional CNEs in a pair have very similar epigenetic profiles, hinting at a functional relationship between them. Taken together, our results support the existence of epistatic interactions between adjacent CNEs that are distance-sensitive and disrupted by transposon insertions and deletions, and contribute to our understanding of the selective forces acting on cis-regulatory elements, which are crucial for elucidating the molecular mechanisms underlying adaptive evolution and human genetic diseases.}, } @article {pmid30184068, year = {2018}, author = {Syme, RA and Tan, KC and Rybak, K and Friesen, TL and McDonald, BA and Oliver, RP and Hane, JK}, title = {Pan-Parastagonospora Comparative Genome Analysis-Effector Prediction and Genome Evolution.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2443-2457}, pmid = {30184068}, issn = {1759-6653}, abstract = {We report a fungal pan-genome study involving Parastagonospora spp., including 21 isolates of the wheat (Triticum aestivum) pathogen Parastagonospora nodorum, 10 of the grass-infecting Parastagonospora avenae, and 2 of a closely related undefined sister species. We observed substantial variation in the distribution of polymorphisms across the pan-genome, including repeat-induced point mutations, diversifying selection and gene gains and losses. We also discovered chromosome-scale inter and intraspecific presence/absence variation of some sequences, suggesting the occurrence of one or more accessory chromosomes or regions that may play a role in host-pathogen interactions. The presence of known pathogenicity effector loci SnToxA, SnTox1, and SnTox3 varied substantially among isolates. Three P. nodorum isolates lacked functional versions for all three loci, whereas three P. avenae isolates carried one or both of the SnTox1 and SnTox3 genes, indicating previously unrecognized potential for discovering additional effectors in the P. nodorum-wheat pathosystem. We utilized the pan-genomic comparative analysis to improve the prediction of pathogenicity effector candidates, recovering the three confirmed effectors among our top-ranked candidates. We propose applying this pan-genomic approach to identify the effector repertoire involved in other host-microbe interactions involving necrotrophic pathogens in the Pezizomycotina.}, } @article {pmid30184067, year = {2018}, author = {Gagnaire, PA and Lamy, JB and Cornette, F and Heurtebise, S and Dégremont, L and Flahauw, E and Boudry, P and Bierne, N and Lapègue, S}, title = {Analysis of Genome-Wide Differentiation between Native and Introduced Populations of the Cupped Oysters Crassostrea gigas and Crassostrea angulata.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2518-2534}, pmid = {30184067}, issn = {1759-6653}, abstract = {The Pacific cupped oyster is genetically subdivided into two sister taxa, Crassostrea gigas and Crassostrea angulata, which are in contact in the north-western Pacific. The nature and origin of their genetic and taxonomic differentiation remains controversial due the lack of known reproductive barriers and the high degree of morphologic similarity. In particular, whether the presence of ecological and/or intrinsic isolating mechanisms contributes to species divergence is unknown. The recent co-introduction of both taxa into Europe offers a unique opportunity to test how genetic differentiation is maintained under new environmental and demographic conditions. We generated a pseudochromosome assembly of the Pacific oyster genome using a combination of BAC-end sequencing and scaffold anchoring to a new high-density linkage map. We characterized genome-wide differentiation between C. angulata and C. gigas in both their native and introduced ranges, and showed that gene flow between species has been facilitated by their recent co-introductions in Europe. Nevertheless, patterns of genomic divergence between species remain highly similar in Asia and Europe, suggesting that the environmental transition caused by the co-introduction of the two species did not affect the genomic architecture of their partial reproductive isolation. Increased genetic differentiation was preferentially found in regions of low recombination. Using historical demographic inference, we show that the heterogeneity of differentiation across the genome is well explained by a scenario whereby recent gene flow has eroded past differentiation at different rates across the genome after a period of geographical isolation. Our results thus support the view that low-recombining regions help in maintaining intrinsic genetic differences between the two species.}, } @article {pmid30184065, year = {2018}, author = {Garry, DJ and Meyer, AJ and Ellefson, JW and Bull, JJ and Ellington, AD}, title = {Predicting Evolution of the Transcription Regulatory Network in a Bacteriophage.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2614-2628}, pmid = {30184065}, issn = {1759-6653}, abstract = {Prediction of evolutionary trajectories has been an elusive goal, requiring a deep knowledge of underlying mechanisms that relate genotype to phenotype plus understanding how phenotype impacts organismal fitness. We tested our ability to predict molecular regulatory evolution in a bacteriophage (T7) whose RNA polymerase (RNAP) was altered to recognize a heterologous promoter differing by three nucleotides from the wild-type promoter. A mutant of wild-type T7 lacking its RNAP gene was passaged on a bacterial strain providing the novel RNAP in trans. Higher fitness rapidly evolved. Predicting the evolutionary trajectory of this adaptation used measured in vitro transcription rates of the novel RNAP on the six promoter sequences capturing all possible one-step pathways between the wild-type and the heterologous promoter sequences. The predictions captured some of the regulatory evolution but failed both in explaining 1) a set of T7 promoters that consistently failed to evolve and 2) some promoter evolution that fell outside the expected one-step pathways. Had a more comprehensive set of transcription assays been undertaken initially, all promoter evolution would have fallen within predicted bounds, but the lack of evolution in some promoters is unresolved. Overall, this study points toward the increasing feasibility of predicting evolution in well-characterized, simple systems.}, } @article {pmid30183407, year = {2018}, author = {Rossant, J}, title = {Genetic Control of Early Cell Lineages in the Mammalian Embryo.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {185-201}, doi = {10.1146/annurev-genet-120116-024544}, pmid = {30183407}, issn = {1545-2948}, abstract = {Establishing the different lineages of the early mammalian embryo takes place over several days and several rounds of cell divisions from the fertilized egg. The resulting blastocyst contains the pluripotent cells of the epiblast, from which embryonic stem cells can be derived, as well as the extraembryonic lineages required for a mammalian embryo to survive in the uterine environment. The dynamics of the cellular and genetic interactions controlling the initiation and maintenance of these lineages in the mouse embryo are increasingly well understood through application of the tools of single-cell genomics, gene editing, and in vivo imaging. Exploring the similarities and differences between mouse and human development will be essential for translation of these findings into new insights into human biology, derivation of stem cells, and improvements in fertility treatments.}, } @article {pmid30183406, year = {2018}, author = {Grover, P and Asa, JS and Campos, EI}, title = {H3-H4 Histone Chaperone Pathways.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {109-130}, doi = {10.1146/annurev-genet-120417-031547}, pmid = {30183406}, issn = {1545-2948}, abstract = {Nucleosomes compact and organize genetic material on a structural level. However, they also alter local chromatin accessibility through changes in their position, through the incorporation of histone variants, and through a vast array of histone posttranslational modifications. The dynamic nature of chromatin requires histone chaperones to process, deposit, and evict histones in different tissues and at different times in the cell cycle. This review focuses on the molecular details of canonical and variant H3-H4 histone chaperone pathways that lead to histone deposition on DNA as they are currently understood. Emphasis is placed on the most established pathways beginning with the folding, posttranslational modification, and nuclear import of newly synthesized H3-H4 histones. Next, we review the deposition of replication-coupled H3.1-H4 in S-phase and replication-independent H3.3-H4 via alternative histone chaperone pathways. Highly specialized histone chaperones overseeing the deposition of histone variants are also briefly discussed.}, } @article {pmid30183405, year = {2018}, author = {Nützmann, HW and Scazzocchio, C and Osbourn, A}, title = {Metabolic Gene Clusters in Eukaryotes.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {159-183}, doi = {10.1146/annurev-genet-120417-031237}, pmid = {30183405}, issn = {1545-2948}, abstract = {In bacteria, more than half of the genes in the genome are organized in operons. In contrast, in eukaryotes, functionally related genes are usually dispersed across the genome. There are, however, numerous examples of functional clusters of nonhomologous genes for metabolic pathways in fungi and plants. Despite superficial similarities with operons (physical clustering, coordinate regulation), these clusters have not usually originated by horizontal gene transfer from bacteria, and (unlike operons) the genes are typically transcribed separately rather than as a single polycistronic message. This clustering phenomenon raises intriguing questions about the origins of clustered metabolic pathways in eukaryotes and the significance of clustering for pathway function. Here we review metabolic gene clusters from fungi and plants, highlight commonalities and differences, and consider how these clusters form and are regulated. We also identify opportunities for future research in the areas of large-scale genomics, synthetic biology, and experimental evolution.}, } @article {pmid30183404, year = {2018}, author = {Misra, JR and Irvine, KD}, title = {The Hippo Signaling Network and Its Biological Functions.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {65-87}, doi = {10.1146/annurev-genet-120417-031621}, pmid = {30183404}, issn = {1545-2948}, support = {K99 HD092553/HD/NICHD NIH HHS/United States ; R01 GM078620/GM/NIGMS NIH HHS/United States ; R01 GM121537/GM/NIGMS NIH HHS/United States ; }, abstract = {Hippo signaling is an evolutionarily conserved network that has a central role in regulating cell proliferation and cell fate to control organ growth and regeneration. It promotes activation of the LATS kinases, which control gene expression by inhibiting the activity of the transcriptional coactivator proteins YAP and TAZ in mammals and Yorkie in Drosophila. Diverse upstream inputs, including both biochemical cues and biomechanical cues, regulate Hippo signaling and enable it to have a key role as a sensor of cells' physical environment and an integrator of growth control signals. Several components of this pathway localize to cell-cell junctions and contribute to regulation of Hippo signaling by cell polarity, cell contacts, and the cytoskeleton. Downregulation of Hippo signaling promotes uncontrolled cell proliferation, impairs differentiation, and is associated with cancer. We review the current understanding of Hippo signaling and highlight progress in the elucidation of its regulatory mechanisms and biological functions.}, } @article {pmid30181663, year = {2018}, author = {Castelle, CJ and Brown, CT and Anantharaman, K and Probst, AJ and Huang, RH and Banfield, JF}, title = {Biosynthetic capacity, metabolic variety and unusual biology in the CPR and DPANN radiations.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {629-645}, doi = {10.1038/s41579-018-0076-2}, pmid = {30181663}, issn = {1740-1534}, abstract = {Candidate phyla radiation (CPR) bacteria and DPANN (an acronym of the names of the first included phyla) archaea are massive radiations of organisms that are widely distributed across Earth's environments, yet we know little about them. Initial indications are that they are consistently distinct from essentially all other bacteria and archaea owing to their small cell and genome sizes, limited metabolic capacities and often episymbiotic associations with other bacteria and archaea. In this Analysis, we investigate their biology and variations in metabolic capacities by analysis of approximately 1,000 genomes reconstructed from several metagenomics-based studies. We find that they are not monolithic in terms of metabolism but rather harbour a diversity of capacities consistent with a range of lifestyles and degrees of dependence on other organisms. Notably, however, certain CPR and DPANN groups seem to have exceedingly minimal biosynthetic capacities, whereas others could potentially be free living. Understanding of these microorganisms is important from the perspective of evolutionary studies and because their interactions with other organisms are likely to shape natural microbiome function.}, } @article {pmid30181647, year = {2018}, author = {}, title = {Molecular test of age highlights difficult questions.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {5}, doi = {10.1038/d41586-018-06165-y}, pmid = {30181647}, issn = {1476-4687}, mesh = {Age Factors ; *Epigenomics ; *Ethics, Professional ; Humans ; Politics ; *Refugees ; }, } @article {pmid30181646, year = {2018}, author = {McCullom, R}, title = {A murdered teen, two million tweets and an experiment to fight gun violence.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {20-22}, doi = {10.1038/d41586-018-06169-8}, pmid = {30181646}, issn = {1476-4687}, mesh = {Adolescent ; Adolescent Behavior/*psychology ; Aggression/psychology ; *Anger ; *Artificial Intelligence ; Chicago ; Drug Overdose/diagnosis/prevention & control ; Female ; *Firearms ; *Grief ; Heroin Dependence ; Homicide/prevention & control/psychology ; Humans ; Machine Learning ; Male ; Motivation ; Reproducibility of Results ; Risk ; *Social Media/statistics & numerical data ; Violence/*prevention & control/*psychology ; Young Adult ; }, } @article {pmid30181645, year = {2018}, author = {Crow, JM}, title = {Why New Zealand is an attractive destination for scientists.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {141-142}, doi = {10.1038/d41586-018-06171-0}, pmid = {30181645}, issn = {1476-4687}, } @article {pmid30181644, year = {2018}, author = {Kumar, R and Peuch, VH and Crawford, JH and Brasseur, G}, title = {Five steps to improve air-quality forecasts.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {27-29}, doi = {10.1038/d41586-018-06150-5}, pmid = {30181644}, issn = {1476-4687}, mesh = {Air Pollution/*adverse effects/*prevention & control ; Atmosphere/chemistry ; Crops, Agricultural/drug effects ; Developing Countries/statistics & numerical data ; Environmental Monitoring/*methods ; Forecasting/*methods ; Humans ; International Cooperation ; Lung Diseases/epidemiology/prevention & control ; Meteorology/methods ; Ozone/adverse effects/analysis ; Public Health/*methods ; }, } @article {pmid30181643, year = {2018}, author = {}, title = {Global warming tops the agenda as climate brings down a third Australian prime minister.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {5-6}, doi = {10.1038/d41586-018-06164-z}, pmid = {30181643}, issn = {1476-4687}, mesh = {Australia ; Coral Reefs ; Droughts ; Environmental Policy/*legislation & jurisprudence ; *Federal Government ; *Global Warming/legislation & jurisprudence/prevention & control ; *Politics ; }, } @article {pmid30181642, year = {2018}, author = {Abbott, A}, title = {European scientists seek 'epigenetic clock' to determine age of refugees.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {15}, doi = {10.1038/d41586-018-06121-w}, pmid = {30181642}, issn = {1476-4687}, mesh = {Adolescent ; *Age Factors ; Aging/*genetics ; Child ; Child, Preschool ; DNA/blood/genetics ; Epigenesis, Genetic/*genetics ; Ethnic Groups/genetics ; Europe ; Forensic Genetics/*methods ; Humans ; Organ Specificity/genetics ; Refugees/*legislation & jurisprudence ; Reproducibility of Results ; Research Personnel ; Workforce ; }, } @article {pmid30181641, year = {2018}, author = {Ferry, G}, title = {Ribosome reader to Royal Society leader: a biologist's road to the Nobel.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {32}, doi = {10.1038/d41586-018-06138-1}, pmid = {30181641}, issn = {1476-4687}, } @article {pmid30181639, year = {2018}, author = {Else, H}, title = {Radical open-access plan could spell end to journal subscriptions.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {17-18}, doi = {10.1038/d41586-018-06178-7}, pmid = {30181639}, issn = {1476-4687}, mesh = {Europe ; Financing, Organized/economics/organization & administration ; Open Access Publishing/economics/*trends ; Periodicals as Topic/*economics ; }, } @article {pmid30181638, year = {2018}, author = {Suzuki, T}, title = {DNA tags used to image sugar-bearing proteins on cells.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {38-40}, doi = {10.1038/d41586-018-06092-y}, pmid = {30181638}, issn = {1476-4687}, } @article {pmid30181637, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {42}, doi = {10.1038/d41586-018-06151-4}, pmid = {30181637}, issn = {1476-4687}, } @article {pmid30181636, year = {2018}, author = {Padma, TV}, title = {Mining and dams exacerbated devastating Kerala floods.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {13-14}, doi = {10.1038/d41586-018-06145-2}, pmid = {30181636}, issn = {1476-4687}, mesh = {Altitude ; Animals ; Conservation of Natural Resources ; *Disasters ; Floods/*mortality ; Geologic Sediments/analysis ; Global Warming ; Hydrology ; India ; *Mining ; Power Plants ; Rain ; Rivers ; Water Movements ; }, } @article {pmid30181635, year = {2018}, author = {Nordling, L}, title = {World Bank pours hundreds of millions into African science.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {16}, doi = {10.1038/d41586-018-06094-w}, pmid = {30181635}, issn = {1476-4687}, mesh = {Africa ; Banking, Personal/*economics ; *International Cooperation ; *Investments ; Research Support as Topic/*economics/trends ; Science/*economics/*organization & administration ; Uncertainty ; }, } @article {pmid30181634, year = {2018}, author = {}, title = {How to make graphene 'snow' in a microwave.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {9}, doi = {10.1038/d41586-018-06103-y}, pmid = {30181634}, issn = {1476-4687}, } @article {pmid30181633, year = {2018}, author = {}, title = {A 'smart' system could upend a decades-old method of cell analysis.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {8}, doi = {10.1038/d41586-018-06119-4}, pmid = {30181633}, issn = {1476-4687}, } @article {pmid30181632, year = {2018}, author = {Tollefson, J}, title = {Enormous wildfires spark scramble to improve fire models.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {16-17}, doi = {10.1038/d41586-018-06090-0}, pmid = {30181632}, issn = {1476-4687}, mesh = {British Columbia ; California ; Disasters/prevention & control/statistics & numerical data ; Forecasting/*methods ; Global Warming/statistics & numerical data ; Human Activities ; *Models, Theoretical ; Wildfires/prevention & control/*statistics & numerical data ; Wind ; }, } @article {pmid30181631, year = {2018}, author = {Maxmen, A}, title = {Experimental Ebola drugs face tough test in war zone.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {14}, doi = {10.1038/d41586-018-06132-7}, pmid = {30181631}, issn = {1476-4687}, mesh = {Antiviral Agents ; Drug Repositioning ; Drugs, Investigational ; *Ebolavirus ; *Hemorrhagic Fever, Ebola ; Humans ; }, } @article {pmid30181630, year = {2018}, author = {}, title = {'Bow ties' break record for bottling up light.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {8}, doi = {10.1038/d41586-018-06141-6}, pmid = {30181630}, issn = {1476-4687}, } @article {pmid30181629, year = {2018}, author = {}, title = {Why the developing gut does the twist.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {8}, doi = {10.1038/d41586-018-06104-x}, pmid = {30181629}, issn = {1476-4687}, } @article {pmid30181628, year = {2018}, author = {}, title = {Canine CRISPR trial raises hopes for humans with deadly disease.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {9}, doi = {10.1038/d41586-018-06142-5}, pmid = {30181628}, issn = {1476-4687}, } @article {pmid30181627, year = {2018}, author = {}, title = {Meal of poo makes naked mole rats motherly.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {9}, doi = {10.1038/d41586-018-06096-8}, pmid = {30181627}, issn = {1476-4687}, } @article {pmid30181626, year = {2018}, author = {}, title = {Earth exhaled, and the 'Great Dying' began.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {8-9}, doi = {10.1038/d41586-018-06062-4}, pmid = {30181626}, issn = {1476-4687}, } @article {pmid30181625, year = {2018}, author = {de Koning-Ward, TF}, title = {Spotlight on proteins that aid malaria.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {41-43}, doi = {10.1038/d41586-018-05977-2}, pmid = {30181625}, issn = {1476-4687}, mesh = {Animals ; *Malaria ; *Parasites ; }, } @article {pmid30181624, year = {2018}, author = {Raine, NE}, title = {An alternative to controversial pesticides still harms bumblebees.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {40-41}, doi = {10.1038/d41586-018-05917-0}, pmid = {30181624}, issn = {1476-4687}, mesh = {Agriculture ; Animals ; Bees ; Conservation of Natural Resources ; Ecology ; *Pesticides ; Pyridines ; *Sulfur Compounds ; }, } @article {pmid30181623, year = {2018}, author = {Sauer, JD}, title = {An immune response with a sweet tooth.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {37-38}, doi = {10.1038/d41586-018-05854-y}, pmid = {30181623}, issn = {1476-4687}, mesh = {Adenosine Diphosphate ; *Bacterial Proteins ; Heptoses ; *Receptors, Immunologic ; }, } @article {pmid30181377, year = {2018}, author = {Mayr, C}, title = {What Are 3' UTRs Doing?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a034728}, pmid = {30181377}, issn = {1943-0264}, abstract = {SUMMARY3' untranslated regions (3' UTRs) of messenger RNAs (mRNAs) are best known to regulate mRNA-based processes, such as mRNA localization, mRNA stability, and translation. In addition, 3' UTRs can establish 3' UTR-mediated protein-protein interactions (PPIs), and thus can transmit genetic information encoded in 3' UTRs to proteins. This function has been shown to regulate diverse protein features, including protein complex formation or posttranslational modifications, but is also expected to alter protein conformations. Therefore, 3' UTR-mediated information transfer can regulate protein features that are not encoded in the amino acid sequence. This review summarizes both 3' UTR functions-the regulation of mRNA and protein-based processes-and highlights how each 3' UTR function was discovered with a focus on experimental approaches used and the concepts that were learned. This review also discusses novel approaches to study 3' UTR functions in the future by taking advantage of recent advances in technology.}, } @article {pmid30181298, year = {2018}, author = {Haffner, MC and Taheri, D and Luidy-Imada, E and Palsgrove, DN and Eich, ML and Netto, GJ and Matoso, A and Nirschl, TR and Zheng, Q and Hicks, JL and Nelson, WG and De Marzo, AM and Marchionni, L and Drake, CG and Yegnasubramanian, S}, title = {Hypomethylation, endogenous retrovirus expression, and interferon signaling in testicular germ cell tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8580-E8582}, pmid = {30181298}, issn = {1091-6490}, support = {P30 CA006973/CA/NCI NIH HHS/United States ; }, mesh = {*Endogenous Retroviruses ; Humans ; Interferons ; Male ; Neoplasms, Germ Cell and Embryonal ; Testicular Neoplasms/*genetics ; }, } @article {pmid30181297, year = {2018}, author = {Stone, ML and Chiappinelli, KB and Li, H and Murphy, LM and Travers, ME and Topper, MJ and Mathios, D and Lim, M and Shih, IM and Wang, TL and Hung, CF and Bhargava, V and Wiehagen, KR and Cowley, GS and Bachman, KE and Strick, R and Strissel, PL and Baylin, SB and Zahnow, CA}, title = {Reply to Haffner et al.: DNA hypomethylation renders tumors more immunogenic.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8583-E8584}, pmid = {30181297}, issn = {1091-6490}, support = {R00 CA204592/CA/NCI NIH HHS/United States ; T32 GM008752/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA ; *DNA Methylation ; Humans ; *Neoplasms ; }, } @article {pmid30181296, year = {2018}, author = {Adida, CL and Lo, A and Platas, MR}, title = {Perspective taking can promote short-term inclusionary behavior toward Syrian refugees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9521-9526}, pmid = {30181296}, issn = {1091-6490}, mesh = {*Altruism ; Female ; Humans ; Male ; *Political Activism ; *Refugees ; Surveys and Questionnaires ; Syria ; Time Factors ; United States ; }, abstract = {Social scientists have shown how easily individuals are moved to exclude outgroup members. Can we foster inclusion instead? This study leverages one of the most significant humanitarian crises of our time to test whether, and under what conditions, American citizens adopt more inclusionary behavior toward Syrian refugees. We conduct a nationally representative survey of over 5,000 American citizens in the weeks leading up to the 2016 presidential election and experimentally test whether a perspective-taking exercise increases inclusionary behavior in the form of an anonymous letter supportive of refugees to be sent to the 45th President of the United States. Our results indicate that the perspective-taking message increases the likelihood of writing such a positive letter by two to five percentage points. By contrast, an informational message had no significant effect on letter writing. The effect of the perspective-taking exercise occurs in the short run only, manifests as a behavioral rather than an attitudinal response, and is strongest among Democrats. However, this effect also appears in the subset of Republican respondents, suggesting that efforts to promote perspective taking may move to action a wide cross-section of individuals.}, } @article {pmid30181295, year = {2018}, author = {Liu, Y and Chakrabarti, B and Saintillan, D and Lindner, A and du Roure, O}, title = {Morphological transitions of elastic filaments in shear flow.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9438-9443}, pmid = {30181295}, issn = {1091-6490}, mesh = {Actin Cytoskeleton/*chemistry/metabolism ; Algorithms ; *Biophysical Phenomena ; *Computer Simulation ; Elasticity ; Hydrodynamics ; Microscopy, Fluorescence ; Models, Theoretical ; Molecular Conformation ; *Rheology ; Thermodynamics ; Viscosity ; }, abstract = {The morphological dynamics, instabilities, and transitions of elastic filaments in viscous flows underlie a wealth of biophysical processes from flagellar propulsion to intracellular streaming and are also key to deciphering the rheological behavior of many complex fluids and soft materials. Here, we combine experiments and computational modeling to elucidate the dynamical regimes and morphological transitions of elastic Brownian filaments in a simple shear flow. Actin filaments are used as an experimental model system and their conformations are investigated through fluorescence microscopy in microfluidic channels. Simulations matching the experimental conditions are also performed using inextensible Euler-Bernoulli beam theory and nonlocal slender-body hydrodynamics in the presence of thermal fluctuations and agree quantitatively with observations. We demonstrate that filament dynamics in this system are primarily governed by a dimensionless elasto-viscous number comparing viscous drag forces to elastic bending forces, with thermal fluctuations playing only a secondary role. While short and rigid filaments perform quasi-periodic tumbling motions, a buckling instability arises above a critical flow strength. A second transition to strongly deformed shapes occurs at a yet larger value of the elasto-viscous number and is characterized by the appearance of localized high-curvature bends that propagate along the filaments in apparent "snaking" motions. A theoretical model for the as yet unexplored onset of snaking accurately predicts the transition and explains the observed dynamics. We present a complete characterization of filament morphologies and transitions as a function of elasto-viscous number and scaled persistence length and demonstrate excellent agreement between theory, experiments, and simulations.}, } @article {pmid30181294, year = {2018}, author = {Sadler, JBA and Wenzel, DM and Williams, LK and Guindo-Martínez, M and Alam, SL and Mercader, JM and Torrents, D and Ullman, KS and Sundquist, WI and Martin-Serrano, J}, title = {A cancer-associated polymorphism in ESCRT-III disrupts the abscission checkpoint and promotes genome instability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8900-E8908}, pmid = {30181294}, issn = {1091-6490}, support = {R01 GM112080/GM/NIGMS NIH HHS/United States ; S10 RR024761/RR/NCRR NIH HHS/United States ; //Department of Health/United Kingdom ; WT102871MA//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; P41 GM103393/GM/NIGMS NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States ; }, mesh = {Calcium-Binding Proteins/metabolism ; Carcinogenesis/genetics ; Cell Cycle Checkpoints/*genetics ; Cell Cycle Proteins/metabolism ; Cell Line, Tumor ; Chromatin/metabolism ; Crystallography, X-Ray ; DNA Damage/genetics ; DNA Replication/genetics ; Endosomal Sorting Complexes Required for Transport/*genetics/metabolism ; Genetic Predisposition to Disease/*genetics ; Genomic Instability/*genetics ; Humans ; Mitosis/genetics ; Neoplasms/*genetics ; Phosphorylation ; Polymorphism, Genetic ; RNA, Small Interfering/metabolism ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {Cytokinetic abscission facilitates the irreversible separation of daughter cells. This process requires the endosomal-sorting complexes required for transport (ESCRT) machinery and is tightly regulated by charged multivesicular body protein 4C (CHMP4C), an ESCRT-III subunit that engages the abscission checkpoint (NoCut) in response to mitotic problems such as persisting chromatin bridges within the midbody. Importantly, a human polymorphism in CHMP4C (rs35094336, CHMP4CT232) increases cancer susceptibility. Here, we explain the structural and functional basis for this cancer association: The CHMP4CT232 allele unwinds the C-terminal helix of CHMP4C, impairs binding to the early-acting ESCRT factor ALIX, and disrupts the abscission checkpoint. Cells expressing CHMP4CT232 exhibit increased levels of DNA damage and are sensitized to several conditions that increase chromosome missegregation, including DNA replication stress, inhibition of the mitotic checkpoint, and loss of p53. Our data demonstrate the biological importance of the abscission checkpoint and suggest that dysregulation of abscission by CHMP4CT232 may synergize with oncogene-induced mitotic stress to promote genomic instability and tumorigenesis.}, } @article {pmid30181293, year = {2018}, author = {Niesner, D and Hauck, M and Shrestha, S and Levchuk, I and Matt, GJ and Osvet, A and Batentschuk, M and Brabec, C and Weber, HB and Fauster, T}, title = {Structural fluctuations cause spin-split states in tetragonal (CH3NH3)PbI3 as evidenced by the circular photogalvanic effect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9509-9514}, pmid = {30181293}, issn = {1091-6490}, abstract = {Lead halide perovskites are used in thin-film solar cells, which owe their high efficiency to the long lifetimes of photocarriers. Various calculations find that a dynamical Rashba effect could significantly contribute to these long lifetimes. This effect is predicted to cause a spin splitting of the electronic bands of inversion-symmetric crystalline materials at finite temperatures, resulting in a slightly indirect band gap. Direct experimental evidence of the existence or the strength of the spin splitting is lacking. Here, we resonantly excite photocurrents in single crystalline ([Formula: see text])[Formula: see text] with circularly polarized light to clarify the existence of spin splittings in the band structure. We observe a circular photogalvanic effect, i.e., the photocurrent depends on the light helicity, in both orthorhombic and tetragonal ([Formula: see text])[Formula: see text] At room temperature, the effect peaks for excitation photon energies [Formula: see text] meV below the direct optical band gap. Temperature-dependent measurements reveal a sign change of the effect at the orthorhombic-tetragonal phase transition, indicating different microscopic origins in the two phases. Within the tetragonal phase, both [Formula: see text] and the amplitude of the circular photogalvanic effect increase with temperature. Our findings support a dynamical Rashba effect in this phase, i.e., a spin splitting caused by thermally induced structural fluctuations which break inversion symmetry.}, } @article {pmid30181292, year = {2018}, author = {Posgai, MT and Tonddast-Navaei, S and Jayasinghe, M and Ibrahim, GM and Stan, G and Herr, AB}, title = {FcαRI binding at the IgA1 CH2-CH3 interface induces long-range conformational changes that are transmitted to the hinge region.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8882-E8891}, pmid = {30181292}, issn = {1091-6490}, support = {R01 DK071802/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Antigens, CD/chemistry/immunology/*metabolism ; Autoantibodies/immunology/*metabolism ; Binding Sites ; COS Cells ; Cercopithecus aethiops ; Computational Biology ; Glomerulonephritis, IGA/immunology/pathology ; Glycosylation ; Humans ; Hydrophobic and Hydrophilic Interactions ; Immunoglobulin A/chemistry/genetics/immunology/*metabolism ; Molecular Dynamics Simulation ; Mutagenesis ; Polysaccharides/immunology ; *Protein Domains ; Receptors, Fc/chemistry/immunology/*metabolism ; Sf9 Cells ; Spodoptera ; Surface Plasmon Resonance ; }, abstract = {IgA effector functions include proinflammatory immune responses triggered upon clustering of the IgA-specific receptor, FcαRI, by IgA immune complexes. FcαRI binds to the IgA1-Fc domain (Fcα) at the CH2-CH3 junction and, except for CH2 L257 and L258, all side-chain contacts are contributed by the CH3 domain. In this study, we used experimental and computational approaches to elucidate energetic and conformational aspects of FcαRI binding to IgA. The energetic contribution of each IgA residue in the binding interface was assessed by alanine-scanning mutagenesis and equilibrium surface plasmon resonance (SPR). As expected, hydrophobic residues central to the binding site have strong energetic contributions to the FcαRI:Fcα interaction. Surprisingly, individual mutation of CH2 residues L257 and L258, found at the periphery of the FcαRI binding site, dramatically reduced binding affinity. Comparison of antibody:receptor complexes involving IgA or its precursor IgY revealed a conserved receptor binding site at the CH2-CH3 junction (or its equivalent). Given the importance of residues near the CH2-CH3 junction, we used coarse-grained Langevin dynamics simulations to understand the functional dynamics in Fcα. Our simulations indicate that FcαRI binding, either in an asymmetric (1:1) or symmetric (2:1) complex with Fcα, propagated long-range conformational changes across the Fc domains, potentially impacting the hinge and Fab regions. Subsequent SPR experiments confirmed that FcαRI binding to the Fcα CH2-CH3 junction altered the kinetics of HAA lectin binding at the IgA1 hinge. Receptor-induced long-distance conformational transitions have important implications for the interaction of aberrantly glycosylated IgA1 with anti-glycan autoantibodies in IgA nephropathy.}, } @article {pmid30181291, year = {2018}, author = {Zhang, YW and Tavoulari, S and Sinning, S and Aleksandrova, AA and Forrest, LR and Rudnick, G}, title = {Structural elements required for coupling ion and substrate transport in the neurotransmitter transporter homolog LeuT.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8854-E8862}, pmid = {30181291}, issn = {1091-6490}, support = {R01 DA007259/DA/NIDA NIH HHS/United States ; R01 DA008213/DA/NIDA NIH HHS/United States ; R01 NS102277/NS/NINDS NIH HHS/United States ; }, mesh = {Binding Sites ; Cations, Monovalent/metabolism ; Cell Membrane/metabolism ; Cysteine/chemistry/metabolism ; Cytoplasm/metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; Molecular Dynamics Simulation ; Mutation ; Plasma Membrane Neurotransmitter Transport Proteins/*chemistry/metabolism ; Protein Binding ; *Protein Domains ; Sodium/*metabolism ; Transcytosis ; Tyrosine/chemistry/metabolism ; }, abstract = {The coupled transport of ions and substrates allows transporters to accumulate substrates using the energy of transmembrane ion gradients and electrical potentials. During transport, conformational changes that switch accessibility of substrate and ion binding sites from one side of the membrane to the other must be controlled so as to prevent uncoupled movement of ions or substrates. In the neurotransmitter:sodium symporter (NSS) family, Na+ stabilizes the transporter in an outward-open state, thus decreasing the likelihood of uncoupled Na+ transport. Substrate binding, in a step essential for coupled transport, must overcome the effect of Na+, allowing intracellular substrate and Na+ release from an inward-open state. However, the specific elements of the protein that mediate this conformational response to substrate binding are unknown. Previously, we showed that in the prokaryotic NSS transporter LeuT, the effect of Na+ on conformation requires the Na2 site, where it influences conformation by fostering interaction between two domains of the protein. Here, we used cysteine accessibility to measure conformational changes of LeuT in Escherichia coli membranes. We identified a conserved tyrosine residue in the substrate binding site required for substrate to convert LeuT to inward-open states by establishing an interaction between the two transporter domains. We further identify additional required interactions between the two transporter domains in the extracellular pathway. Together with our previous work on the conformational effect of Na+, these results identify mechanistic components underlying ion-substrate coupling in NSS transporters.}, } @article {pmid30181290, year = {2018}, author = {Gassaway, BM and Petersen, MC and Surovtseva, YV and Barber, KW and Sheetz, JB and Aerni, HR and Merkel, JS and Samuel, VT and Shulman, GI and Rinehart, J}, title = {PKCε contributes to lipid-induced insulin resistance through cross talk with p70S6K and through previously unknown regulators of insulin signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8996-E9005}, pmid = {30181290}, issn = {1091-6490}, support = {R01 DK113984/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; I01 BX000901/BX/BLRD VA/United States ; R01 GM117230/GM/NIGMS NIH HHS/United States ; R01 DK040936/DK/NIDDK NIH HHS/United States ; P30 DK045735/DK/NIDDK NIH HHS/United States ; T32 GM007205/GM/NIGMS NIH HHS/United States ; F30 DK104596/DK/NIDDK NIH HHS/United States ; P01 DK017433/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Diabetes Mellitus, Type 2/etiology/*metabolism ; Diet, High-Fat/adverse effects ; Disease Models, Animal ; Gene Knockdown Techniques ; Humans ; Insulin/*metabolism ; Insulin Receptor Substrate Proteins/metabolism ; Insulin Resistance/*physiology ; Lipid Metabolism/physiology ; Liver/metabolism ; Phosphorylation ; Protein Kinase C-epsilon/genetics/*metabolism ; Proteomics/methods ; RNA, Small Interfering/metabolism ; Rats ; Receptor, Insulin/metabolism ; Ribosomal Protein S6/metabolism ; Ribosomal Protein S6 Kinases, 70-kDa/*metabolism ; Signal Transduction/physiology ; }, abstract = {Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C ε (PKCε), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high-fat diet produces hepatic insulin resistance through this mechanism, and knockdown of hepatic PKCε protects against high-fat diet-induced hepatic insulin resistance. Here, we employed a systems-level approach to uncover additional signaling pathways involved in high-fat diet-induced hepatic insulin resistance. We used quantitative phosphoproteomics to map global in vivo changes in hepatic protein phosphorylation in chow-fed, high-fat-fed, and high-fat-fed with PKCε knockdown rats to distinguish the impact of lipid- and PKCε-induced protein phosphorylation. This was followed by a functional siRNA-based screen to determine which dynamically regulated phosphoproteins may be involved in canonical insulin signaling. Direct PKCε substrates were identified by motif analysis of phosphoproteomics data and validated using a large-scale in vitro kinase assay. These substrates included the p70S6K substrates RPS6 and IRS1, which suggested cross talk between PKCε and p70S6K in high-fat diet-induced hepatic insulin resistance. These results identify an expanded set of proteins through which PKCε may drive high-fat diet-induced hepatic insulin resistance that may direct new therapeutic approaches for T2D.}, } @article {pmid30181289, year = {2018}, author = {Fang, J and Huang, Y and Mao, G and Yang, S and Rennert, G and Gu, L and Li, H and Li, GM}, title = {Cancer-driving H3G34V/R/D mutations block H3K36 methylation and H3K36me3-MutSα interaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9598-9603}, pmid = {30181289}, issn = {1091-6490}, support = {R01 GM112702/GM/NIGMS NIH HHS/United States ; R21 CA192003/CA/NCI NIH HHS/United States ; }, mesh = {Carcinogenesis/*genetics ; Cell Line, Tumor ; Child ; DNA Mismatch Repair/genetics ; Genomic Instability/genetics ; Glioma/*genetics/pathology ; Glycine/genetics ; HEK293 Cells ; Histone-Lysine N-Methyltransferase/*metabolism ; Histones/*genetics/metabolism ; Humans ; Methylation ; MutS DNA Mismatch-Binding Protein/*metabolism ; Mutation ; Protein Binding/genetics ; Protein Processing, Post-Translational/genetics ; }, abstract = {Somatic mutations on glycine 34 of histone H3 (H3G34) cause pediatric cancers, but the underlying oncogenic mechanism remains unknown. We demonstrate that substituting H3G34 with arginine, valine, or aspartate (H3G34R/V/D), which converts the non-side chain glycine to a large side chain-containing residue, blocks H3 lysine 36 (H3K36) dimethylation and trimethylation by histone methyltransferases, including SETD2, an H3K36-specific trimethyltransferase. Our structural analysis reveals that the H3 "G33-G34" motif is recognized by a narrow substrate channel, and that H3G34/R/V/D mutations impair the catalytic activity of SETD2 due to steric clashes that impede optimal SETD2-H3K36 interaction. H3G34R/V/D mutations also block H3K36me3 from interacting with mismatch repair (MMR) protein MutSα, preventing the recruitment of the MMR machinery to chromatin. Cells harboring H3G34R/V/D mutations display a mutator phenotype similar to that observed in MMR-defective cells. Therefore, H3G34R/V/D mutations promote genome instability and tumorigenesis by inhibiting MMR activity.}, } @article {pmid30181288, year = {2018}, author = {Ruan, Y and Kao, K and Lefebvre, S and Marchesi, A and Corringer, PJ and Hite, RK and Scheuring, S}, title = {Structural titration of receptor ion channel GLIC gating by HS-AFM.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {10333-10338}, pmid = {30181288}, issn = {1091-6490}, mesh = {Bacterial Proteins/*chemistry/metabolism ; Cyanobacteria/chemistry ; Cysteine Loop Ligand-Gated Ion Channel Receptors/*chemistry/metabolism ; Hydrogen-Ion Concentration ; Ion Channel Gating/physiology ; Microscopy, Atomic Force/*methods ; Protein Conformation ; }, abstract = {Gloeobacter violaceus ligand-gated ion channel (GLIC), a proton-gated, cation-selective channel, is a prokaryotic homolog of the pentameric Cys-loop receptor ligand-gated ion channel family. Despite large changes in ion conductance, small conformational changes were detected in X-ray structures of detergent-solubilized GLIC at pH 4 (active/desensitized state) and pH 7 (closed state). Here, we used high-speed atomic force microscopy (HS-AFM) combined with a buffer exchange system to perform structural titration experiments to visualize GLIC gating at the single-molecule level under native conditions. Reference-free 2D classification revealed channels in multiple conformational states during pH gating. We find changes of protein-protein interactions so far elusive and conformational dynamics much larger than previously assumed. Asymmetric pentamers populate early stages of activation, which provides evidence for an intermediate preactivated state.}, } @article {pmid30181287, year = {2018}, author = {Folkmann, AW and Seydoux, G}, title = {Single-molecule study reveals the frenetic lives of proteins in gradients.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9336-9338}, pmid = {30181287}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*physiology ; Cytoplasm/*metabolism ; Proteins/*metabolism ; }, } @article {pmid30181286, year = {2018}, author = {Raynor, J and Chi, H}, title = {Sprouty branches out to control T cell memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9339-9341}, pmid = {30181286}, issn = {1091-6490}, mesh = {Intracellular Signaling Peptides and Proteins ; *Membrane Proteins ; *T-Lymphocytes ; }, } @article {pmid30181285, year = {2018}, author = {Li, H and Fang, Y and Niu, C and Cao, H and Mi, T and Zhu, H and Yuan, J and Zhu, J}, title = {Inhibition of cIAP1 as a strategy for targeting c-MYC-driven oncogenic activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9317-E9324}, pmid = {30181285}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Cell Cycle Proteins/genetics/metabolism ; Cell Line, Tumor ; *Drug Delivery Systems ; Humans ; Inhibitor of Apoptosis Proteins/*antagonists & inhibitors/genetics/metabolism ; Mice ; Neoplasms/*drug therapy/genetics/metabolism/pathology ; Nuclear Proteins/genetics/metabolism ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; Ubiquitination/*drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Protooncogene c-MYC, a master transcription factor, is a major driver of human tumorigenesis. Development of pharmacological agents for inhibiting c-MYC as an anticancer therapy has been a longstanding but elusive goal in the cancer field. E3 ubiquitin ligase cIAP1 has been shown to mediate the activation of c-MYC by destabilizing MAD1, a key antagonist of c-MYC. Here we developed a high-throughput assay for cIAP1 ubiquitination and identified D19, a small-molecule inhibitor of E3 ligase activity of cIAP1. We show that D19 binds to the RING domain of cIAP1 and inhibits the E3 ligase activity of cIAP1 by interfering with the dynamics of its interaction with E2. Blocking cIAP1 with D19 antagonizes c-MYC by stabilizing MAD1 protein in cells. Furthermore, we show that D19 and an improved analog (D19-14) promote c-MYC degradation and inhibit the oncogenic function of c-MYC in cells and xenograft animal models. In contrast, we show that activating E3 ubiquitin ligase activity of cIAP1 by Smac mimetics destabilizes MAD1, the antagonist of MYC, and increases the protein levels of c-MYC. Our study provides an interesting example using chemical biological approaches for determining distinct biological consequences from inhibiting vs. activating an E3 ubiquitin ligase and suggests a potential broad therapeutic strategy for targeting c-MYC in cancer treatment by pharmacologically modulating cIAP1 E3 ligase activity.}, } @article {pmid30181284, year = {2018}, author = {Hout, M}, title = {Americans' occupational status reflects the status of both of their parents.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9527-9532}, pmid = {30181284}, issn = {1091-6490}, mesh = {Adult ; Aged ; *Career Mobility ; Employment/*statistics & numerical data/trends ; Female ; Humans ; Male ; Middle Aged ; Models, Economic ; *Parents ; Sex Factors ; *Socioeconomic Factors ; United States ; }, abstract = {American workers' occupational status strongly reflects the status of their parents. Men and women who grew up in a two-earner or father-breadwinner family achieved occupations that rose 0.5 point for every one-point increase in their parents' statuses (less if their father was absent). Gender differences were small in two-earner families and mother-only families, but men's status persisted more when the father was the sole breadwinner. Intergenerational persistence did not change in the time the data cover (1994-2016). Absolute mobility declined for recent birth cohorts; barely half the men and women born in the 1980s were upwardly mobile compared with two-thirds of those born in the 1940s. The results as described hold for a socioeconomic index (SEI) that scores occupation according to the average pay and credentials of people in the occupation. Most results were the same when occupations were coded by different criteria, but SEI produced the smallest gender differences.}, } @article {pmid30181283, year = {2018}, author = {Shi, R and Russo, J and Tanaka, H}, title = {Origin of the emergent fragile-to-strong transition in supercooled water.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9444-9449}, pmid = {30181283}, issn = {1091-6490}, abstract = {Liquids can be broadly classified into two categories, fragile and strong ones, depending on how their dynamical properties change with temperature. The dynamics of a strong liquid obey the Arrhenius law, whereas the fragile one displays a super-Arrhenius law, with a much steeper slowing down upon cooling. Recently, however, it was discovered that many materials such as water, oxides, and metals do not obey this simple classification, apparently exhibiting a fragile-to-strong transition far above [Formula: see text] Such a transition is particularly well known for water, and it is now regarded as one of water's most important anomalies. This phenomenon has been attributed to either an unusual glass transition behavior or the crossing of a Widom line emanating from a liquid-liquid critical point. Here by computer simulations of two popular water models and through analyses of experimental data, we show that the emergent fragile-to-strong transition is actually a crossover between two Arrhenius regimes with different activation energies, which can be naturally explained by a two-state description of the dynamics. Our finding provides insight into the fragile-to-strong transition observed in a wide class of materials.}, } @article {pmid30181282, year = {2018}, author = {Terekhov, SS and Smirnov, IV and Malakhova, MV and Samoilov, AE and Manolov, AI and Nazarov, AS and Danilov, DV and Dubiley, SA and Osterman, IA and Rubtsova, MP and Kostryukova, ES and Ziganshin, RH and Kornienko, MA and Vanyushkina, AA and Bukato, ON and Ilina, EN and Vlasov, VV and Severinov, KV and Gabibov, AG and Altman, S}, title = {Ultrahigh-throughput functional profiling of microbiota communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9551-9556}, pmid = {30181282}, issn = {1091-6490}, mesh = {Animals ; Anti-Bacterial Agents/metabolism/*pharmacology ; Bacillus pumilus/drug effects/metabolism ; Bacterial Proteins/genetics/metabolism ; Coumarins/metabolism/*pharmacology ; DNA, Bacterial/genetics/isolation & purification ; Drug Resistance, Bacterial/physiology ; Gastrointestinal Microbiome/*drug effects/physiology ; Gene Expression Profiling ; Healthy Volunteers ; High-Throughput Screening Assays/*methods ; Humans ; Lab-On-A-Chip Devices ; Metabolomics/*methods ; Proteomics/methods ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; Single-Cell Analysis/methods ; Staphylococcus aureus/drug effects/physiology ; Ursidae/microbiology ; }, abstract = {Microbiome spectra serve as critical clues to elucidate the evolutionary biology pathways, potential pathologies, and even behavioral patterns of the host organisms. Furthermore, exotic sources of microbiota represent an unexplored niche to discover microbial secondary metabolites. However, establishing the bacterial functionality is complicated by an intricate web of interactions inside the microbiome. Here we apply an ultrahigh-throughput (uHT) microfluidic droplet platform for activity profiling of the entire oral microbial community of the Siberian bear to isolate Bacillus strains demonstrating antimicrobial activity against Staphylococcus aureus Genome mining allowed us to identify antibiotic amicoumacin A (Ami) as responsible for inhibiting the growth of S. aureus Proteomics and metabolomics revealed a unique mechanism of Bacillus self-resistance to Ami, based on a subtle equilibrium of its deactivation and activation by kinase AmiN and phosphatase AmiO, respectively. We developed uHT quantitative single-cell analysis to estimate antibiotic efficacy toward different microbiomes and used it to determine the activity spectra of Ami toward human and Siberian bear microbiota. Thus, uHT microfluidic droplet platform activity profiling is a powerful tool for discovering antibiotics and quantifying external influences on a microbiome.}, } @article {pmid30181281, year = {2018}, author = {Margoni, F and Baillargeon, R and Surian, L}, title = {Infants distinguish between leaders and bullies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8835-E8843}, pmid = {30181281}, issn = {1091-6490}, mesh = {Bullying ; Fear ; Female ; Humans ; Infant ; Infant, Newborn ; Leadership ; Male ; Peer Group ; *Power (Psychology) ; *Psychology, Child ; *Social Behavior ; }, abstract = {We examined whether 21-month-old infants could distinguish between two broad types of social power: respect-based power exerted by a leader (who might be an authority figure with legitimate power, a prestigious individual with merited power, or some combination thereof) and fear-based power exerted by a bully. Infants first saw three protagonists interact with a character who was either a leader (leader condition) or a bully (bully condition). Next, the character gave an order to the protagonists, who initially obeyed; the character then left the scene, and the protagonists either continued to obey (obey event) or no longer did so (disobey event). Infants in the leader condition looked significantly longer at the disobey than at the obey event, suggesting that they expected the protagonists to continue to obey the leader in her absence. In contrast, infants in the bully condition looked equally at the two events, suggesting that they viewed both outcomes as plausible: The protagonists might continue to obey the absent bully to prevent further harm, or they might disobey her because her power over them weakened in her absence. Additional results supported these interpretations: Infants expected obedience when the bully remained in the scene and could harm the protagonists if defied, but they expected disobedience when the order was given by a character with little or no power over the protagonists. Together, these results indicate that by 21 months of age, infants already hold different expectations for subordinates' responses to individuals with respect-based as opposed to fear-based power.}, } @article {pmid30181280, year = {2018}, author = {Jonchhe, S and Pandey, S and Emura, T and Hidaka, K and Hossain, MA and Shrestha, P and Sugiyama, H and Endo, M and Mao, H}, title = {Decreased water activity in nanoconfinement contributes to the folding of G-quadruplex and i-motif structures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9539-9544}, pmid = {30181280}, issn = {1091-6490}, mesh = {DNA/*chemistry ; *G-Quadruplexes ; Models, Chemical ; Nanostructures/chemistry ; *Nucleotide Motifs ; Polyethylene Glycols/chemistry ; Water/*chemistry ; }, abstract = {Due to the small size of a nanoconfinement, the property of water contained inside is rather challenging to probe. Herein, we measured the amount of water molecules released during the folding of individual G-quadruplex and i-motif structures, from which water activities are estimated in the DNA nanocages prepared by 5 × 5 to 7 × 7 helix bundles (cross-sections, 9 × 9 to 15 × 15 nm). We found water activities decrease with reducing cage size. In the 9 × 9-nm cage, water activity was reduced beyond the reach of regular cosolutes such as polyethylene glycol (PEG). With this set of nanocages, we were able to retrieve the change in water molecules throughout the folding trajectory of G-quadruplex or i-motif. We found that water molecules absorbed from the unfolded to the transition states are much fewer than those lost from the transition to the folded states. The overall loss of water therefore drives the folding of G-quadruplex or i-motif in nanocages with reduced water activities.}, } @article {pmid30181279, year = {2018}, author = {Burnett, R and Chen, H and Szyszkowicz, M and Fann, N and Hubbell, B and Pope, CA and Apte, JS and Brauer, M and Cohen, A and Weichenthal, S and Coggins, J and Di, Q and Brunekreef, B and Frostad, J and Lim, SS and Kan, H and Walker, KD and Thurston, GD and Hayes, RB and Lim, CC and Turner, MC and Jerrett, M and Krewski, D and Gapstur, SM and Diver, WR and Ostro, B and Goldberg, D and Crouse, DL and Martin, RV and Peters, P and Pinault, L and Tjepkema, M and van Donkelaar, A and Villeneuve, PJ and Miller, AB and Yin, P and Zhou, M and Wang, L and Janssen, NAH and Marra, M and Atkinson, RW and Tsang, H and Quoc Thach, T and Cannon, JB and Allen, RT and Hart, JE and Laden, F and Cesaroni, G and Forastiere, F and Weinmayr, G and Jaensch, A and Nagel, G and Concin, H and Spadaro, JV}, title = {Global estimates of mortality associated with long-term exposure to outdoor fine particulate matter.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9592-9597}, pmid = {30181279}, issn = {1091-6490}, mesh = {Air Pollutants/*toxicity ; Air Pollution/adverse effects ; Bayes Theorem ; Cohort Studies ; Environmental Exposure/*adverse effects ; Global Burden of Disease/*statistics & numerical data ; Global Health/statistics & numerical data ; Humans ; Noncommunicable Diseases/*mortality ; Particulate Matter/*toxicity ; Proportional Hazards Models ; Risk Assessment ; Time Factors ; }, abstract = {Exposure to ambient fine particulate matter (PM2.5) is a major global health concern. Quantitative estimates of attributable mortality are based on disease-specific hazard ratio models that incorporate risk information from multiple PM2.5 sources (outdoor and indoor air pollution from use of solid fuels and secondhand and active smoking), requiring assumptions about equivalent exposure and toxicity. We relax these contentious assumptions by constructing a PM2.5-mortality hazard ratio function based only on cohort studies of outdoor air pollution that covers the global exposure range. We modeled the shape of the association between PM2.5 and nonaccidental mortality using data from 41 cohorts from 16 countries-the Global Exposure Mortality Model (GEMM). We then constructed GEMMs for five specific causes of death examined by the global burden of disease (GBD). The GEMM predicts 8.9 million [95% confidence interval (CI): 7.5-10.3] deaths in 2015, a figure 30% larger than that predicted by the sum of deaths among the five specific causes (6.9; 95% CI: 4.9-8.5) and 120% larger than the risk function used in the GBD (4.0; 95% CI: 3.3-4.8). Differences between the GEMM and GBD risk functions are larger for a 20% reduction in concentrations, with the GEMM predicting 220% higher excess deaths. These results suggest that PM2.5 exposure may be related to additional causes of death than the five considered by the GBD and that incorporation of risk information from other, nonoutdoor, particle sources leads to underestimation of disease burden, especially at higher concentrations.}, } @article {pmid30181278, year = {2018}, author = {Stepien, P and Johnson, GN}, title = {Plastid terminal oxidase requires translocation to the grana stacks to act as a sink for electron transport.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9634-9639}, pmid = {30181278}, issn = {1091-6490}, support = {BB/C508877/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/genetics ; Brassica/*physiology ; Electron Transport/*physiology ; Oxidoreductases/*metabolism ; Photosynthesis/physiology ; Plants, Genetically Modified ; Salt Tolerance/physiology ; Thylakoid Membrane Proteins/*metabolism ; Thylakoids/*metabolism ; }, abstract = {The plastid terminal oxidase (PTOX) has been shown to be an important sink for photosynthetic electron transport in stress-tolerant plants. However, overexpression studies in stress-sensitive species have previously failed to induce significant activity of this protein. Here we show that overexpression of PTOX from the salt-tolerant brassica species Eutrema salsugineum does not, alone, result in activity, but that overexpressing plants show faster induction and a greater final level of PTOX activity once exposed to salt stress. This implies that an additional activation step is required before activity is induced. We show that that activation involves the translocation of the protein from the unstacked stromal lamellae to the thylakoid grana and a protection of the protein from trypsin digestion. This represents an important activation step and opens up possibilities in the search for stress-tolerant crops.}, } @article {pmid30181277, year = {2018}, author = {Zhang, J and Guan, X and Li, Q and Meredith, AL and Pan, HL and Yan, J}, title = {Glutamate-activated BK channel complexes formed with NMDA receptors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E9006-E9014}, pmid = {30181277}, issn = {1091-6490}, support = {R01 GM127332/GM/NIGMS NIH HHS/United States ; R01 HL102758/HL/NHLBI NIH HHS/United States ; R01 NS078152/NS/NINDS NIH HHS/United States ; T32 GM008181/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Dentate Gyrus/cytology/physiology ; Excitatory Postsynaptic Potentials/*physiology ; Glutamic Acid/*metabolism ; HEK293 Cells ; Humans ; Large-Conductance Calcium-Activated Potassium Channels/genetics/isolation & purification/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neurons/metabolism ; Patch-Clamp Techniques ; Perforant Pathway/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/isolation & purification/*metabolism ; Recombinant Proteins/isolation & purification/metabolism ; Synapses/metabolism ; Synaptic Transmission/physiology ; }, abstract = {The large-conductance calcium- and voltage-activated K+ (BK) channel has a requirement of high intracellular free Ca2+ concentrations for its activation in neurons under physiological conditions. The Ca2+ sources for BK channel activation are not well understood. In this study, we showed by coimmunopurification and colocalization analyses that BK channels form complexes with NMDA receptors (NMDARs) in both rodent brains and a heterologous expression system. The BK-NMDAR complexes are broadly present in different brain regions. The complex formation occurs between the obligatory BKα and GluN1 subunits likely via a direct physical interaction of the former's intracellular S0-S1 loop with the latter's cytosolic regions. By patch-clamp recording on mouse brain slices, we observed BK channel activation by NMDAR-mediated Ca2+ influx in dentate gyrus granule cells. BK channels modulate excitatory synaptic transmission via functional coupling with NMDARs at postsynaptic sites of medial perforant path-dentate gyrus granule cell synapses. A synthesized peptide of the BKα S0-S1 loop region, when loaded intracellularly via recording pipette, abolished the NMDAR-mediated BK channel activation and effect on synaptic transmission. These findings reveal the broad expression of the BK-NMDAR complexes in brain, the potential mechanism underlying the complex formation, and the NMDAR-mediated activation and function of postsynaptic BK channels in neurons.}, } @article {pmid30181276, year = {2018}, author = {Suárez, R and Paolino, A and Fenlon, LR and Morcom, LR and Kozulin, P and Kurniawan, ND and Richards, LJ}, title = {A pan-mammalian map of interhemispheric brain connections predates the evolution of the corpus callosum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9622-9627}, pmid = {30181276}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Connectome ; Corpus Callosum/cytology/diagnostic imaging/*physiology ; Datasets as Topic ; Diffusion Tensor Imaging ; Female ; Magnetic Resonance Imaging ; Mammals/*physiology ; Neocortex/cytology/diagnostic imaging/*physiology ; Neural Pathways/physiology ; }, abstract = {The brain of mammals differs from that of all other vertebrates, in having a six-layered neocortex that is extensively interconnected within and between hemispheres. Interhemispheric connections are conveyed through the anterior commissure in egg-laying monotremes and marsupials, whereas eutherians evolved a separate commissural tract, the corpus callosum. Although the pattern of interhemispheric connectivity via the corpus callosum is broadly shared across eutherian species, it is not known whether this pattern arose as a consequence of callosal evolution or instead corresponds to a more ancient feature of mammalian brain organization. Here we show that, despite cortical axons using an ancestral commissural route, monotremes and marsupials share features of interhemispheric connectivity with eutherians that likely predate the origin of the corpus callosum. Based on ex vivo magnetic resonance imaging and tractography, we found that connections through the anterior commissure in both fat-tailed dunnarts (Marsupialia) and duck-billed platypus (Monotremata) are spatially segregated according to cortical area topography. Moreover, cell-resolution retrograde and anterograde interhemispheric circuit mapping in dunnarts revealed several features shared with callosal circuits of eutherians. These include the layered organization of commissural neurons and terminals, a broad map of connections between similar (homotopic) regions of each hemisphere, and regions connected to different areas (heterotopic), including hyperconnected hubs along the medial and lateral borders of the cortex, such as the cingulate/motor cortex and claustrum/insula. We therefore propose that an interhemispheric connectome originated in early mammalian ancestors, predating the evolution of the corpus callosum. Because these features have been conserved throughout mammalian evolution, they likely represent key aspects of neocortical organization.}, } @article {pmid30181275, year = {2018}, author = {Steinemann, M and Schlosser, A and Jank, T and Aktories, K}, title = {The chaperonin TRiC/CCT is essential for the action of bacterial glycosylating protein toxins like Clostridium difficile toxins A and B.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9580-9585}, pmid = {30181275}, issn = {1091-6490}, mesh = {Animals ; Bacterial Proteins/*metabolism ; Bacterial Toxins/*metabolism ; Chaperonin Containing TCP-1/antagonists & inhibitors/genetics/*metabolism ; Clostridium difficile/pathogenicity/*physiology ; Cytosol/metabolism ; Enterotoxins/*metabolism ; Fibroblasts ; Gene Knockdown Techniques ; Glycosylation ; HSP90 Heat-Shock Proteins/metabolism ; HeLa Cells ; Host-Pathogen Interactions/*physiology ; Humans ; Mice ; RNA, Small Interfering/metabolism ; }, abstract = {Various bacterial protein toxins, including Clostridium difficile toxins A (TcdA) and B (TcdB), attack intracellular target proteins of host cells by glucosylation. After receptor binding and endocytosis, the toxins are translocated into the cytosol, where they modify target proteins (e.g., Rho proteins). Here we report that the activity of translocated glucosylating toxins depends on the chaperonin TRiC/CCT. The chaperonin subunits CCT4/5 directly interact with the toxins and enhance the refolding and restoration of the glucosyltransferase activities of toxins after heat treatment. Knockdown of CCT5 by siRNA and HSF1A, an inhibitor of TRiC/CCT, blocks the cytotoxic effects of TcdA and TcdB. In contrast, HSP90, which is involved in the translocation and uptake of ADP ribosylating toxins, is not involved in uptake of the glucosylating toxins. We show that the actions of numerous glycosylating toxins from various toxin types and different species depend on TRiC/CCT. Our data indicate that the TRiC/CCT chaperonin system is specifically involved in toxin uptake and essential for the action of various glucosylating protein toxins acting intracellularly on target proteins.}, } @article {pmid30181274, year = {2018}, author = {Yan, Q and Lin, M and Huang, W and Teymournejad, O and Johnson, JM and Hays, FA and Liang, Z and Li, G and Rikihisa, Y}, title = {Ehrlichia type IV secretion system effector Etf-2 binds to active RAB5 and delays endosome maturation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8977-E8986}, pmid = {30181274}, issn = {1091-6490}, support = {R01 AI054476/AI/NIAID NIH HHS/United States ; R01 GM074692/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Bacterial Proteins/chemistry/genetics/*metabolism ; Cell Line ; Ehrlichia chaffeensis/*physiology ; Endosomes/*immunology/metabolism ; GTP Phosphohydrolases/metabolism ; Gene Knockdown Techniques ; Host-Pathogen Interactions/immunology ; Humans ; Macaca mulatta ; Phagosomes/*immunology/metabolism ; Protein Binding ; Sequence Alignment ; Type IV Secretion Systems/*metabolism ; rab5 GTP-Binding Proteins/*metabolism ; }, abstract = {Ehrlichia chaffeensis, an obligatory intracellular bacterium, infects monocytes/macrophages by sequestering a regulator of endosomal traffic, the small GTPase RAB5, on its membrane-bound inclusions to avoid routing to host-cell phagolysosomes. How RAB5 is sequestered on ehrlichial inclusions is poorly understood, however. We found that native Ehrlichia translocated factor-2 (Etf-2), a previously predicted effector of the Ehrlichia type IV secretion system, and recombinant Etf-2 (cloned into the Ehrlichia genome) are secreted into the host-cell cytoplasm and localize to ehrlichial inclusions. Ectopically expressed Etf-2-GFP also localized to inclusions and membranes of early endosomes marked with RAB5 and interacted with GTP-bound RAB5 but not with a GDP-bound RAB5. Etf-2, although lacking a RAB GTPase-activating protein (GAP) Tre2-Bub2-Cdc16 (TBC) domain, contains two conserved TBC domain motifs, namely an Arg finger and a Gln finger, and site-directed mutagenesis revealed that both Arg188 and Gln245 are required for Etf-2 localization to early endosomes. The yeast two-hybrid assay and microscale thermophoresis revealed that Etf-2 binds tightly to GTP-bound RAB5 but not to GDP-bound RAB5. However, Etf-2 lacks RAB5-specific GAP activity. Etf-2 localized to bead-containing phagosomes as well as endosomes containing beads coated with the C-terminal fragment of EtpE (entry-triggering protein of Ehrlichia), an Ehrlichia outer-membrane invasin, and significantly delayed RAB5 dissociation from and RAB7 localization to phagosomes/endosomes and RABGAP5 localization to endosomes. Thus, binding of Etf-2 to RAB5-GTP appears to delay RAB5 inactivation by impeding RABGAP5 localization to endosomes. This suggests a unique mechanism by which RAB5 is sequestered on ehrlichial inclusions to benefit bacterial survival and replication.}, } @article {pmid30181273, year = {2018}, author = {Nie, J and Sobel, AH and Shaevitz, DA and Wang, S}, title = {Dynamic amplification of extreme precipitation sensitivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9467-9472}, pmid = {30181273}, issn = {1091-6490}, abstract = {A useful starting hypothesis for predictions of changes in precipitation extremes with climate is that those extremes increase at the same rate as atmospheric moisture does, which is [Formula: see text] following the Clausius-Clapeyron (CC) relation. This hypothesis, however, neglects potential changes in the strengths of atmospheric circulations associated with precipitation extremes. As increased moisture leads to increased precipitation, the increased latent heating may lead to stronger large-scale ascent and thus, additional increase in precipitation, leading to a super-CC scaling. This study investigates this possibility in the context of the 2015 Texas extreme precipitation event using the Column Quasi-Geostrophic (CQG) method. Analogs to this event are simulated in different climatic conditions with varying surface temperature ([Formula: see text]) given the same adiabatic quasigeostrophic forcing. Precipitation in these events exhibits super-CC scaling due to the dynamic contribution associated with increasing ascent due to increased latent heating, an increase with importance that increases with [Formula: see text] The thermodynamic contribution (attributable to increasing water vapor; assuming no change in vertical motion) approximately follows CC as expected, while vertical structure changes of moisture and diabatic heating lead to negative but secondary contributions to the sensitivity, reducing the rate of increase.}, } @article {pmid30181272, year = {2018}, author = {Ho, PP and Lahey, LJ and Mourkioti, F and Kraft, PE and Filareto, A and Brandt, M and Magnusson, KEG and Finn, EE and Chamberlain, JS and Robinson, WH and Blau, HM and Steinman, L}, title = {Engineered DNA plasmid reduces immunity to dystrophin while improving muscle force in a model of gene therapy of Duchenne dystrophy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {E9182-E9191}, pmid = {30181272}, issn = {1091-6490}, support = {R01 HL122332/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *DNA/genetics/pharmacokinetics ; Dependovirus/*genetics ; Disease Models, Animal ; Dystrophin/genetics/immunology/metabolism ; Genetic Therapy/*methods ; *Genetic Vectors/pharmacology ; Male ; Mice ; Mice, Inbred mdx ; Muscle Strength/*genetics/immunology ; Muscular Dystrophy, Duchenne/genetics/immunology/metabolism/*therapy ; *Plasmids/genetics/pharmacology ; }, abstract = {In gene therapy for Duchenne muscular dystrophy there are two potential immunological obstacles. An individual with Duchenne muscular dystrophy has a genetic mutation in dystrophin, and therefore the wild-type protein is "foreign," and thus potentially immunogenic. The adeno-associated virus serotype-6 (AAV6) vector for delivery of dystrophin is a viral-derived vector with its own inherent immunogenicity. We have developed a technology where an engineered plasmid DNA is delivered to reduce autoimmunity. We have taken this approach into humans, tolerizing to myelin proteins in multiple sclerosis and to proinsulin in type 1 diabetes. Here, we extend this technology to a model of gene therapy to reduce the immunogenicity of the AAV vector and of the wild-type protein product that is missing in the genetic disease. Following gene therapy with systemic administration of recombinant AAV6-microdystrophin to mdx/mTRG2 mice, we demonstrated the development of antibodies targeting dystrophin and AAV6 capsid in control mice. Treatment with the engineered DNA construct encoding microdystrophin markedly reduced antibody responses to dystrophin and to AAV6. Muscle force in the treated mice was also improved compared with control mice. These data highlight the potential benefits of administration of an engineered DNA plasmid encoding the delivered protein to overcome critical barriers in gene therapy to achieve optimal functional gene expression.}, } @article {pmid30181271, year = {2018}, author = {Guilbeault, D and Becker, J and Centola, D}, title = {Social learning and partisan bias in the interpretation of climate trends.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9714-9719}, pmid = {30181271}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Aged ; *Bias ; *Climate Change/statistics & numerical data ; Communication ; Conflict (Psychology) ; Cues ; Data Interpretation, Statistical ; Female ; Humans ; Male ; Middle Aged ; Politics ; Social Behavior ; *Social Learning ; Social Support ; Young Adult ; }, abstract = {Vital scientific communications are frequently misinterpreted by the lay public as a result of motivated reasoning, where people misconstrue data to fit their political and psychological biases. In the case of climate change, some people have been found to systematically misinterpret climate data in ways that conflict with the intended message of climate scientists. While prior studies have attempted to reduce motivated reasoning through bipartisan communication networks, these networks have also been found to exacerbate bias. Popular theories hold that bipartisan networks amplify bias by exposing people to opposing beliefs. These theories are in tension with collective intelligence research, which shows that exchanging beliefs in social networks can facilitate social learning, thereby improving individual and group judgments. However, prior experiments in collective intelligence have relied almost exclusively on neutral questions that do not engage motivated reasoning. Using Amazon's Mechanical Turk, we conducted an online experiment to test how bipartisan social networks can influence subjects' interpretation of climate communications from NASA. Here, we show that exposure to opposing beliefs in structured bipartisan social networks substantially improved the accuracy of judgments among both conservatives and liberals, eliminating belief polarization. However, we also find that social learning can be reduced, and belief polarization maintained, as a result of partisan priming. We find that increasing the salience of partisanship during communication, both through exposure to the logos of political parties and through exposure to the political identities of network peers, can significantly reduce social learning.}, } @article {pmid30181270, year = {2018}, author = {}, title = {Correction for Tomasini et al., TAp73 regulates the spindle assembly checkpoint by modulating BubR1 activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8812}, doi = {10.1073/pnas.1814112115}, pmid = {30181270}, issn = {1091-6490}, } @article {pmid30181269, year = {2018}, author = {Lu, H and Fermaintt, CS and Cherepanova, NA and Gilmore, R and Yan, N and Lehrman, MA}, title = {Mammalian STT3A/B oligosaccharyltransferases segregate N-glycosylation at the translocon from lipid-linked oligosaccharide hydrolysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9557-9562}, pmid = {30181269}, issn = {1091-6490}, support = {R01 AR067135/AR/NIAMS NIH HHS/United States ; R01 GM038545/GM/NIGMS NIH HHS/United States ; R01 GM043768/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Endoplasmic Reticulum/metabolism ; Exodeoxyribonucleases/genetics/metabolism ; Gene Knockout Techniques ; Glycosylation ; Hexosyltransferases/genetics/*metabolism ; Humans ; Hydrolysis ; Isoenzymes ; Lipopolysaccharides/*metabolism ; Membrane Proteins/genetics/*metabolism ; Mice ; Oligosaccharides/*metabolism ; Phosphoproteins/genetics/metabolism ; Protein Processing, Post-Translational/*physiology ; Protein Transport/physiology ; }, abstract = {Oligosaccharyltransferases (OSTs) N-glycosylate proteins by transferring oligosaccharides from lipid-linked oligosaccharides (LLOs) to asparaginyl residues of Asn-Xaa-Ser/Thr acceptor sequons. Mammals have OST isoforms with STT3A or STT3B catalytic subunits for cotranslational or posttranslational N-glycosylation, respectively. OSTs also hydrolyze LLOs, forming free oligosaccharides (fOSs). It has been unclear whether hydrolysis is due to one or both OSTs, segregated from N-glycosylation, and/or regulated. Transfer and hydrolysis were assayed in permeabilized HEK293 kidney and Huh7.5.1 liver cells lacking STT3A or STT3B. Transfer by both STT3A-OST and STT3B-OST with synthetic acceptors was robust. LLO hydrolysis by STT3B-OST was readily detected and surprisingly modulated: Without acceptors, STT3B-OST hydrolyzed Glc3Man9GlcNAc2-LLO but not Man9GlcNAc2-LLO, yet it hydrolyzed both LLOs with acceptors present. In contrast, LLO hydrolysis by STT3A-OST was negligible. STT3A-OST however may be regulatory, because it suppressed STT3B-OST-dependent fOSs. TREX1, a negative innate immunity factor that diminishes immunogenic fOSs derived from LLOs, acted through STT3B-OST as well. In summary, only STT3B-OST hydrolyzes LLOs, depending upon LLO quality and acceptor site occupancy. TREX1 and STT3A suppress STT3B-OST-dependent fOSs. Without strict kinetic limitations during posttranslational N-glycosylation, STT3B-OST can thus moonlight for LLO hydrolysis. In contrast, the STT3A-OST/translocon complex preserves LLOs for temporally fastidious cotranslational N-glycosylation.}, } @article {pmid30181268, year = {2018}, author = {Krinner, G and Flanner, MG}, title = {Striking stationarity of large-scale climate model bias patterns under strong climate change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9462-9466}, pmid = {30181268}, issn = {1091-6490}, abstract = {Because all climate models exhibit biases, their use for assessing future climate change requires implicitly assuming or explicitly postulating that the biases are stationary or vary predictably. This hypothesis, however, has not been, and cannot be, tested directly. This work shows that under very large climate change the bias patterns of key climate variables exhibit a striking degree of stationarity. Using only correlation with a model's preindustrial bias pattern, a model's 4xCO2 bias pattern is objectively and correctly identified among a large model ensemble in almost all cases. This outcome would be exceedingly improbable if bias patterns were independent of climate state. A similar result is also found for bias patterns in two historical periods. This provides compelling and heretofore missing justification for using such models to quantify climate perturbation patterns and for selecting well-performing models for regional downscaling. Furthermore, it opens the way to extending bias corrections to perturbed states, substantially broadening the range of justified applications of climate models.}, } @article {pmid30181267, year = {2018}, author = {Edwards, RWJ and Celia, MA}, title = {Infrastructure to enable deployment of carbon capture, utilization, and storage in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8815-E8824}, pmid = {30181267}, issn = {1091-6490}, abstract = {In February 2018, the United States enacted significant financial incentives for carbon capture, utilization, and storage (CCUS) that will make capture from the lowest-capture-cost sources economically viable. The largest existing low-capture-cost opportunity is from ethanol fermentation at biorefineries in the Midwest. An impediment to deployment of carbon capture at ethanol biorefineries is that most are not close to enhanced oil recovery (EOR) fields or other suitable geological formations in which the carbon dioxide could be stored. Therefore, we analyze the viability of a pipeline network to transport carbon dioxide from Midwest ethanol biorefineries to the Permian Basin in Texas, which has the greatest current carbon dioxide demand for EOR and large potential for expansion. We estimate capture and transport costs and perform economic analysis for networks under three pipeline financing scenarios representing different combinations of commercial and government finance. Without government finance, we find that a network earning commercial rates of return would not be viable. With 50% government financing for pipelines, 19 million tons of carbon dioxide per year could be captured and transported profitably. Thirty million tons per year could be captured with full government pipeline financing, which would double global anthropogenic carbon capture and increase the United States' carbon dioxide EOR industry by 50%. Such a development would face challenges, including coordination between governments and industries, pressing timelines, and policy uncertainties, but is not unprecedented. This represents an opportunity to considerably increase CCUS in the near-term and develop long-term transport infrastructure facilitating future growth.}, } @article {pmid30181266, year = {2018}, author = {}, title = {Correction for Tsigkou et al., Engineered vascularized bone grafts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8811}, doi = {10.1073/pnas.1813106115}, pmid = {30181266}, issn = {1091-6490}, } @article {pmid30181265, year = {2018}, author = {Käufer, C and Chhatbar, C and Bröer, S and Waltl, I and Ghita, L and Gerhauser, I and Kalinke, U and Löscher, W}, title = {Chemokine receptors CCR2 and CX3CR1 regulate viral encephalitis-induced hippocampal damage but not seizures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8929-E8938}, pmid = {30181265}, issn = {1091-6490}, mesh = {Animals ; CD11b Antigen/immunology/metabolism ; CX3C Chemokine Receptor 1/genetics/*immunology ; Disease Models, Animal ; Encephalitis, Viral/*immunology/pathology/virology ; Female ; Hippocampus/cytology/immunology/pathology ; Humans ; Leukocyte Common Antigens/immunology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microglia/cytology/immunology/pathology ; Monocytes/immunology/pathology ; Neurodegenerative Diseases/*immunology/pathology ; Neurons/immunology/pathology ; Receptors, CCR2/genetics/*immunology ; Seizures/*immunology/pathology/virology ; Theilovirus/isolation & purification ; }, abstract = {Viral encephalitis is a major risk factor for the development of seizures, epilepsy, and hippocampal damage with associated cognitive impairment, markedly reducing quality of life in survivors. The mechanisms underlying seizures and hippocampal neurodegeneration developing during and after viral encephalitis are only incompletely understood, hampering the development of preventive treatments. Recent findings suggest that brain invasion of blood-born monocytes may be critically involved in both seizures and brain damage in response to encephalitis, whereas the relative role of microglia, the brain's resident immune cells, in these processes is not clear. CCR2 and CX3CR1 are two chemokine receptors that regulate the responses of myeloid cells, such as monocytes and microglia, during inflammation. We used Ccr2-KO and Cx3cr1-KO mice to understand the role of these receptors in viral encephalitis-associated seizures and neurodegeneration, using the Theiler's virus model of encephalitis in C57BL/6 mice. Our results show that CCR2 as well as CX3CR1 plays a key role in the accumulation of myeloid cells in the CNS and activation of hippocampal myeloid cells upon infection. Furthermore, by using Cx3cr1-creER+/-tdTomatoSt/Wt reporter mice, we show that, with regard to CD45 and CD11b expression, some microglia become indistinguishable from monocytes during CNS infection. Interestingly, the lack of CCR2 or CX3CR1 receptors was associated with almost complete prevention of hippocampal damage but did not prevent seizure development after viral CNS infection. These data are compatible with the hypothesis that CNS inflammatory mechanism(s) other than the infiltrating myeloid cells trigger the development of seizures during viral encephalitis.}, } @article {pmid30181264, year = {2018}, author = {Sjaastad, LE and Fay, EJ and Fiege, JK and Macchietto, MG and Stone, IA and Markman, MW and Shen, S and Langlois, RA}, title = {Distinct antiviral signatures revealed by the magnitude and round of influenza virus replication in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9610-9615}, pmid = {30181264}, issn = {1091-6490}, support = {K22 AI110581/AI/NIAID NIH HHS/United States ; T32 AI007313/AI/NIAID NIH HHS/United States ; UL1 TR002494/TR/NCATS NIH HHS/United States ; T32 HL007741/HL/NHLBI NIH HHS/United States ; R01 AI132962/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Dogs ; Epithelial Cells/immunology/virology ; Gene Expression Profiling/methods ; HEK293 Cells ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions/*immunology ; Humans ; Influenza A virus/isolation & purification/*physiology ; Influenza, Human/immunology/pathology/*virology ; Interferons/immunology ; Lung/cytology/immunology/pathology/*virology ; Madin Darby Canine Kidney Cells ; Mice, Inbred C57BL ; RNA, Viral/isolation & purification ; Sequence Analysis, DNA ; Virus Replication/*immunology ; }, abstract = {Influenza virus has a broad cellular tropism in the respiratory tract. Infected epithelial cells sense the infection and initiate an antiviral response. To define the antiviral response at the earliest stages of infection we used a series of single-cycle reporter viruses. These viral probes demonstrated cells in vivo harbor a range in magnitude of virus replication. Transcriptional profiling of cells supporting different levels of replication revealed tiers of IFN-stimulated gene expression. Uninfected cells and cells with blunted replication expressed a distinct and potentially protective antiviral signature, while cells with high replication expressed a unique reserve set of antiviral genes. Finally, we used these single-cycle reporter viruses to determine the antiviral landscape during virus spread, which unveiled disparate protection of epithelial cell subsets mediated by IFN in vivo. Together these results highlight the complexity of virus-host interactions within the infected lung and suggest that magnitude and round of replication tune the antiviral response.}, } @article {pmid30181263, year = {2018}, author = {}, title = {Correction to Supporting Information for Delvendahl et al., Reduced endogenous Ca2+ buffering speeds active zone Ca2+ signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8813-E8814}, doi = {10.1073/pnas.1813283115}, pmid = {30181263}, issn = {1091-6490}, } @article {pmid30181262, year = {2018}, author = {Pritchard, HAT and Pires, PW and Yamasaki, E and Thakore, P and Earley, S}, title = {Nanoscale remodeling of ryanodine receptor cluster size underlies cerebral microvascular dysfunction in Duchenne muscular dystrophy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {41}, pages = {E9745-E9752}, pmid = {30181262}, issn = {1091-6490}, support = {K99 HL140106/HL/NHLBI NIH HHS/United States ; R01 HL091905/HL/NHLBI NIH HHS/United States ; R01 HL137852/HL/NHLBI NIH HHS/United States ; R01 HL139585/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Calcium Signaling ; Cells, Cultured ; Cerebral Arteries/metabolism/*pathology ; Dystrophin/physiology ; Homeostasis ; Large-Conductance Calcium-Activated Potassium Channels/*metabolism ; Male ; Mice ; Mice, Inbred mdx ; Muscle Contraction ; Muscle, Smooth, Vascular/metabolism/*pathology ; Muscular Dystrophy, Animal/metabolism/*pathology ; Muscular Dystrophy, Duchenne/metabolism/*pathology ; Nanotechnology ; Ryanodine Receptor Calcium Release Channel/*metabolism ; Sarcoplasmic Reticulum/metabolism ; Vasoconstriction ; }, abstract = {Duchenne muscular dystrophy (DMD) results from mutations in the gene encoding dystrophin which lead to impaired function of skeletal and cardiac muscle, but little is known about the effects of the disease on vascular smooth muscle cells (SMCs). Here we used the mdx mouse model to study the effects of mutant dystrophin on the regulation of cerebral artery and arteriole SMC contractility, focusing on an important Ca2+-signaling pathway composed of type 2 ryanodine receptors (RyR2s) on the sarcoplasmic reticulum (SR) and large-conductance Ca2+-activated K+ (BK) channels on the plasma membrane. Nanoscale superresolution image analysis revealed that RyR2 and BKα were organized into discrete clusters, and that the mean size of RyR2 clusters that colocalized with BKα was larger in SMCs from mdx mice (∼62 RyR2 monomers) than in controls (∼40 RyR2 monomers). We further found that the frequency and signal mass of spontaneous, transient Ca2+-release events through SR RyR2s ("Ca2+ sparks") were greater in SMCs from mdx mice. Patch-clamp electrophysiological recordings indicated a corresponding increase in Ca2+-dependent BK channel activity. Using pressure myography, we found that cerebral pial arteries and parenchymal arterioles from mdx mice failed to develop appreciable spontaneous myogenic tone. Inhibition of RyRs with tetracaine and blocking of BK channels with paxilline restored myogenic tone to control levels, demonstrating that enhanced RyR and BK channel activity is responsible for the diminished pressure-induced constriction of arteries and arterioles from mdx mice. We conclude that increased size of RyR2 protein clusters in SMCs from mdx mice increases Ca2+ spark and BK channel activity, resulting in cerebral microvascular dysfunction.}, } @article {pmid30181261, year = {2018}, author = {Deline, B and Greenwood, JM and Clark, JW and Puttick, MN and Peterson, KJ and Donoghue, PCJ}, title = {Evolution of metazoan morphological disparity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8909-E8918}, pmid = {30181261}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; *Biological Evolution ; Fossils ; Gene Expression Regulation/*physiology ; Genome Size/*physiology ; MicroRNAs/*physiology ; Proteins/genetics ; }, abstract = {The animal kingdom exhibits a great diversity of organismal form (i.e., disparity). Whether the extremes of disparity were achieved early in animal evolutionary history or clades continually explore the limits of possible morphospace is subject to continuing debate. Here we show, through analysis of the disparity of the animal kingdom, that, even though many clades exhibit maximal initial disparity, arthropods, chordates, annelids, echinoderms, and mollusks have continued to explore and expand the limits of morphospace throughout the Phanerozoic, expanding dramatically the envelope of disparity occupied in the Cambrian. The "clumpiness" of morphospace occupation by living clades is a consequence of the extinction of phylogenetic intermediates, indicating that the original distribution of morphologies was more homogeneous. The morphological distances between phyla mirror differences in complexity, body size, and species-level diversity across the animal kingdom. Causal hypotheses of morphologic expansion include time since origination, increases in genome size, protein repertoire, gene family expansion, and gene regulation. We find a strong correlation between increasing morphological disparity, genome size, and microRNA repertoire, but no correlation to protein domain diversity. Our results are compatible with the view that the evolution of gene regulation has been influential in shaping metazoan disparity whereas the invasion of terrestrial ecospace appears to represent an additional gestalt, underpinning the post-Cambrian expansion of metazoan disparity.}, } @article {pmid30181260, year = {2018}, author = {Shen, K and Sabatini, DM}, title = {Ragulator and SLC38A9 activate the Rag GTPases through noncanonical GEF mechanisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9545-9550}, pmid = {30181260}, issn = {1091-6490}, support = {R01 CA103866/CA/NCI NIH HHS/United States ; R01 CA129105/CA/NCI NIH HHS/United States ; R37 AI047389/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Amino Acid Transport Systems/*metabolism ; Energy Metabolism/physiology ; Guanine Nucleotide Exchange Factors/*metabolism ; HEK293 Cells ; Humans ; Intracellular Membranes/metabolism ; Lysosomes/metabolism ; Mechanistic Target of Rapamycin Complex 1/*metabolism ; Monomeric GTP-Binding Proteins/*metabolism ; Phosphorylation/physiology ; Protein Binding/physiology ; Protein Multimerization/physiology ; Recombinant Proteins/metabolism ; Signal Transduction/*physiology ; }, abstract = {The mechanistic target of rapamycin complex 1 (mTORC1) growth pathway detects nutrients through a variety of sensors and regulators that converge on the Rag GTPases, which form heterodimers consisting of RagA or RagB tightly bound to RagC or RagD and control the subcellular localization of mTORC1. The Rag heterodimer uses a unique "locking" mechanism to stabilize its active (GTPRagA-RagCGDP) or inactive (GDPRagA-RagCGTP) nucleotide states. The Ragulator complex tethers the Rag heterodimer to the lysosomal surface, and the SLC38A9 transmembrane protein is a lysosomal arginine sensor that upon activation stimulates mTORC1 activity through the Rag GTPases. How Ragulator and SLC38A9 control the nucleotide loading state of the Rag GTPases remains incompletely understood. Here we find that Ragulator and SLC38A9 are each unique guanine exchange factors (GEFs) that collectively push the Rag GTPases toward the active state. Ragulator triggers GTP release from RagC, thus resolving the locked inactivated state of the Rag GTPases. Upon arginine binding, SLC38A9 converts RagA from the GDP- to the GTP-loaded state, and therefore activates the Rag GTPase heterodimer. Altogether, Ragulator and SLC38A9 act on the Rag GTPases to activate the mTORC1 pathway in response to nutrient sufficiency.}, } @article {pmid30181256, year = {2018}, author = {Beans, C}, title = {Core Concept: Environmental DNA helps researchers track pythons and other stealthy creatures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8843-8845}, pmid = {30181256}, issn = {1091-6490}, mesh = {Animals ; Boidae/*physiology ; DNA/*analysis ; Florida ; *Introduced Species ; }, } @article {pmid30181195, year = {2018}, author = {Joyce, GF and Szostak, JW}, title = {Protocells and RNA Self-Replication.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a034801}, pmid = {30181195}, issn = {1943-0264}, abstract = {SUMMARYThe general notion of an "RNA world" is that, in the early development of life on the Earth, genetic continuity was assured by the replication of RNA, and RNA molecules were the chief agents of catalytic function. Assuming that all of the components of RNA were available in some prebiotic locale, these components could have assembled into activated nucleotides that condensed to form RNA polymers, setting the stage for the chemical replication of polynucleotides through RNA-templated RNA polymerization. If a sufficient diversity of RNAs could be copied with reasonable rate and fidelity, then Darwinian evolution would begin with RNAs that facilitated their own reproduction enjoying a selective advantage. The concept of a "protocell" refers to a compartment where replication of the primitive genetic material took place and where primitive catalysts gave rise to products that accumulated locally for the benefit of the replicating cellular entity. Replication of both the protocell and its encapsulated genetic material would have enabled natural selection to operate based on the differential fitness of competing cellular entities, ultimately giving rise to modern cellular life.}, } @article {pmid30181194, year = {2018}, author = {Zatz, M and Dupere, S}, title = {Careers in Science and Grant Administration: View from the National Institutes of Health.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a032847}, pmid = {30181194}, issn = {1943-0264}, abstract = {Scientist administrators at the National Institutes of Health fall into two categories: program officers and scientific review officers. Program officers provide advice to applicants and grantees, make funding recommendations, oversee grantees' research progress, and facilitate research opportunities in emerging areas of science. Scientific review officers oversee all aspects of the initial (peer) review of grant applications.}, } @article {pmid30181072, year = {2018}, author = {Krüger, T and Schuster, S and Engstler, M}, title = {Beyond Blood: African Trypanosomes on the Move.}, journal = {Trends in parasitology}, volume = {34}, number = {12}, pages = {1056-1067}, doi = {10.1016/j.pt.2018.08.002}, pmid = {30181072}, issn = {1471-5007}, abstract = {While the African trypanosomes are among the best-studied parasites, almost everything we know about them is based on the brucei group, which includes the human-infective sleeping sickness parasites and the causative agent of the cattle plague nagana. The past decades have seen an ever-more detailed molecular dissection of Trypanosoma brucei, which today is an accepted cell biological model system. Therefore, recent work on some fundamental aspects of trypanosome biology surprises, as we realise that our knowledge about parasite motility and tropism in the changing host microenvironments is far from definitive. In this review, we highlight a few examples of neglected parasitological questions, which may open (or reopen) a new chapter of trypanosome research.}, } @article {pmid30181071, year = {2018}, author = {Baker, CH and Welburn, SC}, title = {The Long Wait for a New Drug for Human African Trypanosomiasis.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {818-827}, doi = {10.1016/j.pt.2018.08.006}, pmid = {30181071}, issn = {1471-5007}, support = {16/136/33//Department of Health/United Kingdom ; }, mesh = {Drug Development/economics/standards/*trends ; Humans ; Time ; *Trypanocidal Agents/standards ; Trypanosomiasis, African/*drug therapy ; }, abstract = {Human African trypanosomiasis (HAT) is responsible for around 3000 reported cases each year. Treatments for HAT are expensive and problematic to administer, and available drugs are old and less than ideal, some with high levels of toxicity that result in debilitating and, in some cases, fatal side effects. Treatment options are limited, with only one drug, eflornithine, introduced in the last 28 years. Here we examine the limitations of current chemotherapeutic approaches to manage HAT, the constraints to new drug development exploring drug failures and new drugs on the horizon, and consider the epidemiological, political, social, and economic factors influencing drug development.}, } @article {pmid30181062, year = {2019}, author = {de Jonge, PA and Nobrega, FL and Brouns, SJJ and Dutilh, BE}, title = {Molecular and Evolutionary Determinants of Bacteriophage Host Range.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {51-63}, doi = {10.1016/j.tim.2018.08.006}, pmid = {30181062}, issn = {1878-4380}, abstract = {The host range of a bacteriophage is the taxonomic diversity of hosts it can successfully infect. Host range, one of the central traits to understand in phages, is determined by a range of molecular interactions between phage and host throughout the infection cycle. While many well studied model phages seem to exhibit a narrow host range, recent ecological and metagenomics studies indicate that phages may have specificities that range from narrow to broad. There is a growing body of studies on the molecular mechanisms that enable phages to infect multiple hosts. These mechanisms, and their evolution, are of considerable importance to understanding phage ecology and the various clinical, industrial, and biotechnological applications of phage. Here we review knowledge of the molecular mechanisms that determine host range, provide a framework defining broad host range in an evolutionary context, and highlight areas for additional research.}, } @article {pmid30180924, year = {2018}, author = {Thaller, MC and D'Andrea, MM and Marmo, P and Civitareale, C and Casu, F and Migliore, L}, title = {Sphingomonas turrisvirgatae sp. nov., an agar-degrading species isolated from freshwater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2794-2799}, doi = {10.1099/ijsem.0.002896}, pmid = {30180924}, issn = {1466-5034}, mesh = {Agar/metabolism ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/*microbiology ; Italy ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/chemistry ; Sphingomonas/*classification/genetics/isolation & purification ; Ubiquinone/analogs & derivatives/chemistry ; Wetlands ; }, abstract = {A yellow pigmented and agar-pitting colony was isolated from a water sample obtained from a drainage ditch within a disused system of constructed wetlands. The strain was purified and named MCT13T. This rod-shaped, Gram-negative, oxidase- and catalase-positive, aerobic, non-spore-forming, and non-motile strain formed round colonies and grew optimally at pH 7.5±0.2, at 28-30 °C on LB agar, with 0-0.5 % NaCl. The 16S rRNA gene sequence analysis placed the MCT13T isolate within the Sphingomonas (sensu stricto) cluster. The DNA G+C content was 65.3 %. The only observed ubiquinone was Q10. The major fatty acids included C17 : 1ω6c and C18 : 1ω7c/C18 : 1ω6c. The major polar lipids were sphingoglycolipid, diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The major polyamine was spermidine. The 16S rRNA gene phylogenetic analysis performed on the whole sequence, showed the closest relative of MCT13T to be Sphingomonas koreensis (98.52 %); however, there are several genotypic and phenotypic differences between the novel isolate and the type strain JSS26T of S. koreensis. On the basis of these results, strain MCT13T represents a novel species in the genus Sphingomonas, for which the name Sphingomonas turrisvirgatae sp. nov. is proposed. The type strain is MCT13T (=DSM 105457T=BAC RE RSCIC 7T).}, } @article {pmid30180909, year = {2018}, author = {Dunham, CM and Burger, AL and Hileman, BM and Chance, EA}, title = {Learning receptive awareness via neurofeedback in stressed healthcare providers: a prospective pilot investigation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {645}, pmid = {30180909}, issn = {1756-0500}, mesh = {*Awareness ; Electroencephalography ; Humans ; *Neurofeedback ; Nurses/*psychology ; Physicians/*psychology ; Pilot Projects ; Prospective Studies ; }, abstract = {OBJECTIVE: Because physicians and nurses are commonly stressed, Bispectral Index™ (BIS) neurofeedback, following trainer instructions, was used to learn to lower the electroencephalography-derived BIS value, indicating that a state of receptive awareness (relaxed alertness) had been achieved.

RESULTS: Ten physicians/nurses participated in 21 learning days with 9 undergoing ≤ 3 days. The BIS-nadir for the 21 days was decreased (88.7) compared to baseline (97.0; p < 0.01). From 21 wellbeing surveys, moderately-to-extremely rated stress responses were a feeling of irritation 38.1%; nervousness 14.3%; over-reacting 28.6%; tension 66.7%; being overwhelmed 38.1%; being drained 38.1%; and people being too demanding 52.4% (57.1% had ≥ 2 stress indicators). Quite a bit-to-extremely rated positive-affect responses were restful sleep 28.6%; energetic 0%; and alert 47.6% (90.5% had ≥ 2 positive-affect responses rated as slightly-to-moderately). For 1 subject who underwent 4 learning days, mean BIS was lower on day 4 (95.1) than on day 1 (96.8; p < 0.01). The wellbeing score increased 23.3% on day 4 (37) compared to day 1 (30). Changes in BIS values provide evidence that brainwave self-regulation can be learned and may manifest with wellbeing. These findings suggest that stress and impairments in positive-affect are common in physicians/nurses. Trial Registration ClinicalTrials.gov NCT03152331. Registered May 15, 2017.}, } @article {pmid30180908, year = {2018}, author = {Farokhi, A and van Vugt, RM and Hoekzema, R and Nurmohamed, MT}, title = {Multicentric reticulohistiocytosis: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {647}, pmid = {30180908}, issn = {1756-0500}, mesh = {Adult ; Arthritis ; Female ; Histiocytes ; Histiocytosis, Non-Langerhans-Cell/*diagnostic imaging/therapy ; Humans ; Philippines ; Positron Emission Tomography Computed Tomography ; }, abstract = {BACKGROUND: Multicentric reticulohistiocytosis is a rare form of non-langerhans cell histiocytosis presenting with skin changes and erosive arthritis. Infiltration of histiocytes and multinucleated giant cells are typical histological findings and confirm the diagnosis.

CASE PRESENTATION: This case report describes a newly diagnosed case of multicentric reticulohistiocytosis in a healthy 26-year-old female originally from the Philippines. Eruption of papules and nodules on the hands and pain in multiple joints were the main complaints at the initial presentation. Radiographical findings of erosions in the small hand and feet joints were impressive. Initial histological findings did not match the clinical image, although later the clinical diagnosis was supported by histological findings in additional biopsies.

CONCLUSIONS: Although initial histological findings did not match the clinical image, additional biopsies were valuable to confirm the diagnosis.}, } @article {pmid30180900, year = {2018}, author = {Sirisena, ND and Samaranayake, N and Dissanayake, VHW}, title = {Relative normalized luciferase activity for the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {643}, pmid = {30180900}, issn = {1756-0500}, support = {AP/3/2/2015/PG/07//University of Colombo/ ; UGC/DRIC/PG/2015(i)/CMB/01//University Grants Commission, Sri Lanka/ ; }, mesh = {3' Untranslated Regions ; Alleles ; Breast Neoplasms/*genetics ; DNA-Binding Proteins/*genetics ; Female ; Genes, Regulator ; Genetic Predisposition to Disease ; Humans ; Luciferases/*metabolism ; *Polymorphism, Single Nucleotide ; Repressor Proteins/*genetics ; }, abstract = {OBJECTIVE: The data presented herein represents the preliminary results of the functional assays of a recently conducted larger study in which two single nucleotide polymorphisms (SNPs) [XRCC2:rs3218550 and PHB:rs6917] were significantly associated with risk of breast cancer among Sri Lankan postmenopausal women. The rs3218550 T allele and rs6917 A allele were found to increase breast cancer risk by 1.5-fold and 1.4-fold, respectively. Both SNPs are located in the 3'untranslated region (3'UTR) of the respective genes. It was hypothesized that these non-coding SNPs may be exerting some transcriptional regulatory effects on gene expression. Their putative functional effects were further investigated by generating bioluminescent recombinant experimental reporter gene constructs carrying the ancestral and variant alleles of these 2 SNPs, transiently transfecting them in MCF-7 breast cancer cell lines and performing dual-luciferase reporter gene assays to measure the luminescent signals.

DATA DESCRIPTION: The normalized relative luciferase activity for the recombinant vector constructs carrying the ancestral and variant alleles for XRCC2:rs3218550 and PHB:rs6917 are presented herein. This data might be of relevance to other researchers involved in delineating the functional mechanisms of SNPs located in the 3'UTR of the XRCC2 and PHB breast cancer related genes.}, } @article {pmid30180886, year = {2018}, author = {Chappell, S and Patel, T and Guetta-Baranes, T and Sang, F and Francis, PT and Morgan, K and Brookes, KJ}, title = {Observations of extensive gene expression differences in the cerebellum and potential relevance to Alzheimer's disease.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {646}, pmid = {30180886}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Alzheimer Disease/*metabolism/pathology ; Brain ; Cerebellum/*metabolism ; Cerebral Cortex/metabolism ; Female ; Humans ; Male ; Middle Aged ; Pilot Projects ; *Transcriptome ; }, abstract = {OBJECTIVES: In order to determine how gene expression is altered in disease it is of fundamental importance that the global distribution of gene expression levels across the disease-free brain are understood and how differences between tissue types might inform tissue choice for investigation of altered expression in disease state. The aim of this pilot project was to use RNA-sequencing to investigate gene expression differences between five general areas of post-mortem human brain (frontal, temporal, occipital, parietal and cerebellum), and in particular changes in gene expression in the cerebellum compared to cortex regions for genes relevant to Alzheimer's disease, as the cerebellum is largely preserved from disease pathology and could be an area of interest for neuroprotective pathways.

RESULTS: General gene expression profiles were found to be similar between cortical regions of the brain, however the cerebellum presented a distinct expression profile. Focused exploration of gene expression for genes associated with Alzheimer's disease suggest that those involved in the immunity pathway show little expression in the brain. Furthermore some Alzheimer's disease associated genes display significantly different expression in the cerebellum compared with other brain regions, which might indicate potential neuroprotective measures.}, } @article {pmid30180876, year = {2018}, author = {Gunadi, and Karina, SM and Dwihantoro, A}, title = {Outcomes in patients with Hirschsprung disease following definitive surgery.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {644}, pmid = {30180876}, issn = {1756-0500}, mesh = {Adolescent ; Child ; Child, Preschool ; Constipation ; *Digestive System Surgical Procedures ; Female ; Hirschsprung Disease/*surgery ; Humans ; Indonesia ; Infant ; Infant, Newborn ; Male ; Postoperative Complications ; Retrospective Studies ; Treatment Outcome ; }, abstract = {OBJECTIVE: Several pull-through procedures have been described for Hirschsprung disease (HSCR) with varying outcomes. We aimed to describe the outcomes in HSCR patients < 18 year of age who underwent surgical procedures at Dr. Sardjito Hospital, Yogyakarta, Indonesia from January 2013 to December 2014.

RESULTS: We utilized 67 HSCR patients, of whom 49 (73%) were males and 18 (27%) females. Neonatal presentation was seen in 57 cases (85%) and most patients (98.5%) had short-segment HSCR. The clinical manifestations were mainly abdominal distension (94%) and delayed passage of meconium (45%). The most common definitive treatment performed was transanal endorectal pull-through (TEPT) (54%), followed by Soave (18%) and Duhamel (13%) procedures. Enterocolitis occurred in 13% of the HSCR patients after endorectal pull-through, but did not reach a significant level (p-value = 0.65), while the constipation rate was significantly higher in HSCR patients who underwent posterior neurectomy compared with those other procedures (OR = 15.5, 95% CI = 1.8-132.5; p-value = 0.019). In conclusions, most HSCR patients in Indonesia were diagnosed in the neonatal period and underwent the TEPT procedure. Furthermore, the risk of constipation is increased in HSCR patients following posterior neurectomy compared with other definitive surgical techniques.}, } @article {pmid30180875, year = {2018}, author = {Sazhnev, V and DeKrey, GK}, title = {The growth and infectivity of Leishmania major is not altered by in vitro exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {642}, pmid = {30180875}, issn = {1756-0500}, mesh = {Animals ; Female ; Leishmania major/*drug effects/pathogenicity ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, SCID ; Polychlorinated Dibenzodioxins/*pharmacology/toxicity ; }, abstract = {OBJECTIVE: The numbers of Leishmania major parasites in foot lesions of C57Bl/6, BALB/c or SCID mice can be significantly reduced by pre-exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). One potential mechanism to explain this enhanced resistance to infection is that TCDD is directly toxic to L. major. This potential mechanism was addressed by exposing L. major promastigotes and amastigotes to TCDD in vitro and examining their subsequent proliferation and infectivity.

RESULTS: We found no significant change in the rate of in vitro L. major proliferation (promastigotes or amastigotes) after TCDD exposure at concentrations up to 100 nM. Moreover, in vitro TCDD exposure did not significantly alter the ability of L. major to infect mice, trigger lesion formation, or survive in those lesions.}, } @article {pmid30180844, year = {2018}, author = {Salis, P and Roux, N and Soulat, O and Lecchini, D and Laudet, V and Frédérich, B}, title = {Ontogenetic and phylogenetic simplification during white stripe evolution in clownfishes.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {90}, pmid = {30180844}, issn = {1741-7007}, abstract = {BACKGROUND: Biologists have long been fascinated by the striking diversity of complex color patterns in tropical reef fishes. However, the origins and evolution of this diversity are still poorly understood. Disentangling the evolution of simple color patterns offers the opportunity to dissect both ultimate and proximate causes underlying color diversity.

RESULTS: Here, we study clownfishes, a tribe of 30 species within the Pomacentridae that displays a relatively simple color pattern made of zero to three vertical white stripes on a dark body background. Mapping the number of white stripes on the evolutionary tree of clownfishes reveals that their color pattern diversification results from successive caudal to rostral losses of stripes. Moreover, we demonstrate that stripes always appear with a rostral to caudal stereotyped sequence during larval to juvenile transition. Drug treatments (TAE 684) during this period leads to a dose-dependent loss of stripes, demonstrating that white stripes are made of iridophores and that these cells initiate the stripe formation. Surprisingly, juveniles of several species (e.g., Amphiprion frenatus) have supplementary stripes when compared to their respective adults. These stripes disappear caudo-rostrally during the juvenile phase leading to the definitive color pattern. Remarkably, the reduction of stripe number over ontogeny matches the sequences of stripe losses during evolution, showing that color pattern diversification among clownfish lineages results from changes in developmental processes. Finally, we reveal that the diversity of striped patterns plays a key role for species recognition.

CONCLUSIONS: Overall, our findings illustrate how developmental, ecological, and social processes have shaped the diversification of color patterns during the radiation of an emblematic coral reef fish lineage.}, } @article {pmid30180805, year = {2018}, author = {Weerasekera, D and Stengel, F and Sticht, H and de Mattos Guaraldi, AL and Burkovski, A and Azevedo Antunes, C}, title = {The C-terminal coiled-coil domain of Corynebacterium diphtheriae DIP0733 is crucial for interaction with epithelial cells and pathogenicity in invertebrate animal model systems.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {106}, pmid = {30180805}, issn = {1471-2180}, abstract = {BACKGROUND: Corynebacterium diphtheriae is the etiologic agent of diphtheria and different systemic infections. The bacterium has been classically described as an extracellular pathogen. However, a number of studies revealed its ability to invade epithelial cells, indicating a more complex pathogen-host interaction. The molecular mechanisms controlling and facilitating internalization of C. diphtheriae still remains unclear. Recently, the DIP0733 transmembrane protein was found to play an important role in the interaction with matrix proteins and cell surfaces, nematode colonization, cellular internalization and induction of cell death.

RESULTS: In this study, we identified a number of short linear motifs and structural elements of DIP0733 with putative importance in virulence, using bioinformatic approaches. A C-terminal coiled-coil region of the protein was considered particularly important, since it was found only in DIP0733 homologs in pathogenic Corynebacterium species but not in non-pathogenic corynebacteria. Infections of epithelial cells and transepithelial resistance assays revealed that bacteria expressing the truncated form of C. diphtheriae DIP0733 and C. glutamicum DIP0733 homolog are less virulent, while the fusion of the coiled-coil sequence to the DIP0733 homolog from C. glutamicum resulted in increased pathogenicity. These results were supported by nematode killing assays and experiments using wax moth larvae as invertebrate model systems.

CONCLUSIONS: Our data indicate that the coil-coiled domain of DIP0733 is crucial for interaction with epithelial cells and pathogenicity in invertebrate animal model systems.}, } @article {pmid30180804, year = {2018}, author = {Du, X and Li, W and Sheng, L and Deng, Y and Wang, Y and Zhang, W and Yu, K and Jiang, J and Fang, W and Guan, Z and Chen, F and Chen, S}, title = {Over-expression of chrysanthemum CmDREB6 enhanced tolerance of chrysanthemum to heat stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {178}, pmid = {30180804}, issn = {1471-2229}, support = {31672192//National Natural Science Foundation of China/ ; BE2017318//Program for Key Research and Development, Jiangsu, China/ ; }, mesh = {Amino Acid Sequence ; Chrysanthemum ; Gene Expression Regulation, Plant/*physiology ; *Hot Temperature ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Sequence Alignment ; Stress, Physiological/*genetics ; Transcription Factors/chemistry/*genetics/metabolism ; }, abstract = {BACKGROUND: Chrysanthemum is among the top ten traditional flowers in China, and one of the four major cut flowers in the world, but the growth of chrysanthemum is severely restricted by high temperatures which retard growth and cause defects in flowers. DREB (dehydration-responsive element-binding) transcription factors play important roles in the response to abiotic and biotic stresses. However, whether the DREB A-6 subgroup is involved in heat tolerance has not been reported conclusively.

RESULT: In the present study, CmDREB6 was cloned from chrysanthemum (Chrysanthemum morifolium) 'Jinba'. CmDREB6, containing a typical AP2/ERF domain, was classed into the DREB A-6 subgroup and shared highest homology with Cichorium intybus L. CiDREB6 (73%). CmDREB6 was expressed at its highest levels in the leaf. The CmDREB6 protein localized to the nucleus. Based on the yeast one hybrid assay, CmDREB6 showed transcription activation activity in yeast, and the transcriptional activation domain was located in the 3 'end ranging from 230 to 289 amino acids residues. CmDREB6 overexpression enhanced the tolerance of chrysanthemum to heat. The survival rate of two transgenic lines was as high as 85%, 50%, respectively, in contrast to 3.8% of wild-type (WT). Over-expression of CmDREB6 promoted the expression of CmHsfA4, CmHSP90, and the active oxygen scavenging genes CmSOD and CmCAT.

CONCLUSION: In this study, DREB A-6 subgroup gene CmDREB6 was cloned from chrysanthemum 'Jinba'. Overexpression of CmDREB6 enhanced heat tolerance of chrysanthemum by regulating genes involved in the heat shock response and ROS homeogenesis.}, } @article {pmid30180802, year = {2018}, author = {Ott, A and Schnable, JC and Yeh, CT and Wu, L and Liu, C and Hu, HC and Dalgard, CL and Sarkar, S and Schnable, PS}, title = {Linked read technology for assembling large complex and polyploid genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {651}, pmid = {30180802}, issn = {1471-2164}, support = {Not applicable//Office of Biotechnology, Iowa State University/ ; Not applicable//Plant Sciences Institute, Iowa State University (US)/ ; DGE1247194//National Science Foundation/ ; }, mesh = {*Genome, Plant ; High-Throughput Nucleotide Sequencing/*methods ; Plant Leaves/*genetics ; *Polyploidy ; Sequence Analysis, DNA/*methods ; Zea mays/*genetics ; }, abstract = {BACKGROUND: Short read DNA sequencing technologies have revolutionized genome assembly by providing high accuracy and throughput data at low cost. But it remains challenging to assemble short read data, particularly for large, complex and polyploid genomes. The linked read strategy has the potential to enhance the value of short reads for genome assembly because all reads originating from a single long molecule of DNA share a common barcode. However, the majority of studies to date that have employed linked reads were focused on human haplotype phasing and genome assembly.

RESULTS: Here we describe a de novo maize B73 genome assembly generated via linked read technology which contains ~ 172,000 scaffolds with an N50 of 89 kb that cover 50% of the genome. Based on comparisons to the B73 reference genome, 91% of linked read contigs are accurately assembled. Because it was possible to identify errors with > 76% accuracy using machine learning, it may be possible to identify and potentially correct systematic errors. Complex polyploids represent one of the last grand challenges in genome assembly. Linked read technology was able to successfully resolve the two subgenomes of the recent allopolyploid, proso millet (Panicum miliaceum). Our assembly covers ~ 83% of the 1 Gb genome and consists of 30,819 scaffolds with an N50 of 912 kb.

CONCLUSIONS: Our analysis provides a framework for future de novo genome assemblies using linked reads, and we suggest computational strategies that if implemented have the potential to further improve linked read assemblies, particularly for repetitive genomes.}, } @article {pmid30180801, year = {2018}, author = {Heydari, M and Miclotte, G and Van de Peer, Y and Fostier, J}, title = {BrownieAligner: accurate alignment of Illumina sequencing data to de Bruijn graphs.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {311}, pmid = {30180801}, issn = {1471-2105}, support = {G0C3914N//The Research Foundation - Flanders (FWO)/ ; }, mesh = {*Algorithms ; Computational Biology/*methods ; *Computer Graphics ; *Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Programming Languages ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Aligning short reads to a reference genome is an important task in many genome analysis pipelines. This task is computationally more complex when the reference genome is provided in the form of a de Bruijn graph instead of a linear sequence string.

RESULTS: We present a branch and bound alignment algorithm that uses the seed-and-extend paradigm to accurately align short Illumina reads to a graph. Given a seed, the algorithm greedily explores all branches of the tree until the optimal alignment path is found. To reduce the search space we compute upper bounds to the alignment score for each branch and discard the branch if it cannot improve the best solution found so far. Additionally, by using a two-pass alignment strategy and a higher-order Markov model, paths in the de Bruijn graph that do not represent a subsequence in the original reference genome are discarded from the search procedure.

CONCLUSIONS: BrownieAligner is applied to both synthetic and real datasets. It generally outperforms other state-of-the-art tools in terms of accuracy, while having similar runtime and memory requirements. Our results show that using the higher-order Markov model in BrownieAligner improves the accuracy, while the branch and bound algorithm reduces runtime. BrownieAligner is written in standard C++11 and released under GPL license. BrownieAligner relies on multithreading to take advantage of multi-core/multi-CPU systems. The source code is available at: https://github.com/biointec/browniealigner.}, } @article {pmid30180800, year = {2018}, author = {Vanneste, K and Garlant, L and Broeders, S and Van Gucht, S and Roosens, NH}, title = {Application of whole genome data for in silico evaluation of primers and probes routinely employed for the detection of viral species by RT-qPCR using dengue virus as a case study.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {312}, pmid = {30180800}, issn = {1471-2105}, support = {0000754//This work was supported by the project ORIENT-EXPRESS funded by the Scientific Institute of Public Health (WIV-ISP RP-PJ - Belgium)/ ; }, mesh = {*Computer Simulation ; DNA Primers/*analysis/genetics ; Dengue/*diagnosis/virology ; Dengue Virus/classification/*genetics/isolation & purification ; *Genome, Viral ; Humans ; RNA, Viral/*genetics ; Real-Time Polymerase Chain Reaction/*methods ; }, abstract = {BACKGROUND: Viral infection by dengue virus is a major public health problem in tropical countries. Early diagnosis and detection are increasingly based on quantitative reverse transcriptase real-time polymerase chain reaction (RT-qPCR) directed against genomic regions conserved between different isolates. Genetic variation can however result in mismatches of primers and probes with their targeted nucleic acid regions. Whole genome sequencing allows to characterize and track such changes, which in turn enables to evaluate, optimize, and (re-)design novel and existing RT-qPCR methods. The immense amount of available sequence data renders this however a labour-intensive and complex task.

RESULTS: We present a bioinformatics approach that enables in silico evaluation of primers and probes intended for routinely employed RT-qPCR methods. This approach is based on analysing large amounts of publically available whole genome data, by first employing BLASTN to mine the genomic regions targeted by the RT-qPCR method(s), and afterwards using BLASTN-SHORT to evaluate whether primers and probes will anneal based on a set of simple in silico criteria. Using dengue virus as a case study, we evaluated 18 published RT-qPCR methods using more than 3000 publically available genomes in the NCBI Virus Variation Resource, and provide a systematic overview of method performance based on in silico sensitivity and specificity.

CONCLUSIONS: We provide a comprehensive overview of dengue virus RT-qPCR method performance that will aid appropriate method selection allowing to take specific measures that aim to contain and prevent viral spread in afflicted regions. Notably, we find that primer-template mismatches at their 3' end may represent a general issue for dengue virus RT-qPCR detection methods that merits more attention in their development process. Our approach is also available as a public tool, and demonstrates how utilizing genomic data can provide meaningful insights in an applied public health setting such as the detection of viral species in human diagnostics.}, } @article {pmid30180799, year = {2018}, author = {Cardoso-Gustavson, P and Saka, MN and Pessoa, EM and Palma-Silva, C and Pinheiro, F}, title = {Unidirectional transitions in nectar gain and loss suggest food deception is a stable evolutionary strategy in Epidendrum (Orchidaceae): insights from anatomical and molecular evidence.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {179}, pmid = {30180799}, issn = {1471-2229}, support = {440367/2014-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 0588/12-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 300927/2016-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 300819/2016-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 300927/2016-9//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 0469-13-0//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {*Biological Evolution ; DNA, Chloroplast/genetics ; DNA, Plant/genetics ; Food Chain ; Orchidaceae/*anatomy & histology/genetics/*physiology ; Phylogeny ; Plant Nectar/*analysis ; *Pollination ; }, abstract = {BACKGROUND: Nectar gain and loss are important flower transitions observed in angiosperms, and are particularly common in orchids. To understand such transitions, the availability of detailed anatomical data and species-level phylogenies are crucial. We investigated the evolution of food deception in Epidendrum, one of the largest orchid genera, using genus phylogeny to map transitions between nectar gain and loss among different clades. Associations between anatomical and histochemical changes and nectar gain and loss were examined using fresh material available from 27 species. The evolution of nectar presence/absence in Epidendrum species was investigated in a phylogenetic framework of 47 species, using one nuclear and five plastid DNA regions available from GenBank and sequenced in this study.

RESULTS: The presence or absence of nectar was strongly associated with changes in the inner epidermal tissues of nectaries. Nectar-secreting species have unornamented epidermal tissue, in contrast to the unicellular trichomes found on the epidermis of food deceptive species. Bayesian tests confirmed that transitions occurred preferentially from nectar presence to nectar absence across the Epidendrum phylogeny. In addition, independent nectar loss events were found across the phylogeny, suggesting a lack of constraint for these transitions.

CONCLUSIONS: Ornamented nectaries may play an important role in the deceptive pollination strategy by secreting volatile organic compounds and providing tactile stimuli to pollinators. The recurrent and apparently irreversible pattern of nectar loss in Epidendrum suggests that food deception may constitute an alternative evolutionarily stable strategy, as observed in other orchid groups.}, } @article {pmid30180798, year = {2018}, author = {Yoon, S and Kim, D and Kang, K and Park, WJ}, title = {TraRECo: a greedy approach based de novo transcriptome assembler with read error correction using consensus matrix.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {653}, pmid = {30180798}, issn = {1471-2164}, support = {NRF-2016R1D1A1B03933651//National Research Foundation of Korea/ ; }, mesh = {Animals ; *Computational Biology ; Embryonic Stem Cells/cytology/*metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Sequence Analysis, DNA/*methods ; *Software ; *Transcriptome ; }, abstract = {BACKGROUND: The challenges when developing a good de novo transcriptome assembler include how to deal with read errors and sequence repeats. Almost all de novo assemblers utilize a de Bruijn graph, with which complexity grows linearly with data size while suffering from errors and repeats. Although one can correct the errors by inspecting the topological structure of the graph, this is not an easy task when there are too many branches. Two research directions are to improve either the graph reliability or the path search precision, and in this study, we focused on the former.

RESULTS: We present TraRECo, a greedy approach to de novo assembly employing error-aware graph construction. In the proposed approach, we built contigs by direct read alignment within a distance margin and performed a junction search to construct splicing graphs. While doing so, a contig of length l was represented by a 4 × l matrix (called a consensus matrix), in which each element was the base count of the aligned reads so far. A representative sequence was obtained by taking the majority in each column of the consensus matrix to be used for further read alignment. Once the splicing graphs had been obtained, we used IsoLasso to find paths with a noticeable read depth. The experiments using real and simulated reads show that the method provided considerable improvement in sensitivity and moderately better performance when comparing sensitivity and precision. This was achieved by the error-aware graph construction using the consensus matrix, with which the reads having errors were made usable for the graph construction (otherwise, they might have been eventually discarded). This improved the quality of the coverage depth information used in the subsequent path search step and finally the reliability of the graph.

CONCLUSIONS: De novo assembly is mainly used to explore undiscovered isoforms and must be able to represent as many reads as possible in an efficient way. In this sense, TraRECo provides us with a potential alternative for improving graph reliability even though the computational burden is much higher than the single k-mer in the de Bruijn graph approach.}, } @article {pmid30180797, year = {2018}, author = {He, L and Yu, L and Li, B and Du, N and Guo, S}, title = {The effect of exogenous calcium on cucumber fruit quality, photosynthesis, chlorophyll fluorescence, and fast chlorophyll fluorescence during the fruiting period under hypoxic stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {180}, pmid = {30180797}, issn = {1471-2229}, support = {31401919//National Natural Science Foundation of China/ ; 31471869//National Natural Science Foundation of China/ ; 14DZ2282100//Key Project of Science and Technology Commission of Shanghai/ ; G2014070201//Shanghai Agriculture Applied Technology Development Program/ ; Hu Nong Qing Zi No. 2016-1-10//Young Talents Plan in Shang-hai Agricultural System/ ; }, mesh = {Anaerobiosis ; Calcium/*pharmacology ; Chlorophyll/*metabolism ; Cucumis sativus/*drug effects/growth & development/metabolism ; Fluorescence ; Fruit/*drug effects/growth & development/physiology ; Photosynthesis/*drug effects ; }, abstract = {BACKGROUND: Plants often suffer from hypoxic stress during waterlogging and hydroponic culturing. This study investigated the response of cucumber (Cucumis sativus L.) plant growth parameters, leaf photosynthesis, chlorophyll fluorescence, fast chlorophyll a fluorescence transient (OJIP), and fruit quality parameters to hypoxic stress alleviated by exogenous calcium. During the fruiting period, cucumber plants were exposed to hypoxia and hypoxia + Ca2+ treatment (4 mM Ca2+) for 9 d.

RESULT: Exogenous calcium application enhanced the biomass and fruit quality of hypoxic stressed cucumber and also increased the net photosynthesis rate, stomatal conductance, intercellular CO2 concentration, maximum quantum efficiency of photosystem II photochemistry, actual photochemical efficiency of PSII, photochemical quenching coefficient, and non-photochemical quenching coefficient. Additionally, measurement of chlorophyll a fluorescence transients showed the positive K- and L-bands were more pronounced in leaves treated with hypoxia compared with those with hypoxia + Ca2+, indicating that hypoxic treatment induced uncoupling of the oxygen-evolving complex and inhibited electron transport beyond plastoquinone pool (Qa, Qb) including possible constraints on the reduction of end electron acceptors of photosystem I. Exogenous calcium can reduce these stress-induced damages in cucumber.

CONCLUSION: This research focused the effect of exogenous calcium on cucumber photosynthesis during the fruiting period under hypoxic stress. Hypoxic stress might impair the photosynthetic electron-transport chain from the donor side of PSII up to the reduction of end acceptors of PSI, and exogenous calcium enhanced electron transport capacity and reduced hypoxic damage of cucumber leaves.}, } @article {pmid30180796, year = {2018}, author = {Das, S and Barooah, M}, title = {Characterization of siderophore producing arsenic-resistant Staphylococcus sp. strain TA6 isolated from contaminated groundwater of Jorhat, Assam and its possible role in arsenic geocycle.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {104}, pmid = {30180796}, issn = {1471-2180}, abstract = {BACKGROUND: Microorganisms specifically bacteria play a crucial role in arsenic mobilization and its distribution in aquatic systems. Although bacteria are well known for their active participation in the different biogeochemical cycles, the role of these bacteria in regulating the concentration of arsenic in Brahmaputra valley has not been investigated in detail.

RESULTS: In this paper, we report the isolation of an arsenic resistant bacterium TA6 which can efficiently reduce arsenate. The isolate identified as Staphylococcus sp. TA6 based on the molecular and chemotaxonomic identification (FAME) showed resistance to the high concentration of both arsenate and arsenite (As(III) = 30 mM; As(V) = 250 mM), along with cross-tolerance to other heavy metals viz., Hg2+, Cd2+, Co2+, Ni2+, Cr2+. The bacterium also had a high siderophore activity (78.7 ± 0.004 μmol) that positively correlated with its ability to resist arsenic. The isolate, Staphylococcus sp. TA6 displayed high bio-transformation ability and reduced 2 mM As(V) initially added into As(III) in a period of 72 h with 88.2% efficiency. The characterization of arsenate reductase enzyme with NADPH coupled assay showed the highest activity at pH 5.5 and temperature of 50 °C.

CONCLUSIONS: This study demonstrates the role of an isolate, Staphylococcus sp. TA6, in the biotransformation of arsenate to arsenite. The presence of ars operon along with the high activity of the arsenate reductase and siderophore production in this isolate may have played an important role in mobilizing arsenate to arsenite and thus increasing the toxicity of arsenic in the aquatic systems of the Brahmaputra valley.}, } @article {pmid30180795, year = {2018}, author = {Yu, H and Liang, D and Tian, E and Zheng, L and Kjellberg, F}, title = {Plant geographic phenotypic variation drives diversification in its associated community of a phytophagous insect and its parasitoids.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {134}, pmid = {30180795}, issn = {1471-2148}, support = {31670395; 31630008; 31370409//National Natural Science Foundation of China/International ; S2013020012814//Natural Science Foundation of Guangdong Province/International ; }, mesh = {Animals ; *Biological Variation, Population ; Female ; Ficus/anatomy & histology/genetics/*parasitology ; *Geography ; Inflorescence/anatomy & histology/physiology ; Microsatellite Repeats/genetics ; Oviposition/physiology ; Parasites/*physiology ; Pollination ; Sample Size ; Wasps/*parasitology/*physiology ; }, abstract = {BACKGROUND: While the communities constituted by phytophageous insects and their parasites may represent half of all terrestrial animal species, understanding their diversification remains a major challenge. A neglected idea is that geographic phenotypic variation in a host plant may lead to heterogeneous evolutionary responses of the different members of the associated communities. This could result in diversification on a host plant by ecological speciation in some species, leading to geographic variation in community composition. In this study we investigated geographic variation of inflorescence receptacle size in a plant, Ficus hirta, and how the hymenopteran community feeding in the inflorescences has responded. Our predictions were: 1) Inflorescence size variation affects wasp species differently depending on how they access oviposition sites. 2) In some affected lineages of wasps, we may observe vicariant, parapatric species adapted to different inflorescence sizes.

RESULTS: We show that fig (the enclosed inflorescence of Ficus) wall thickness varies geographically. The fig-entering pollinating wasp was not affected, while the parasites ovipositing through the fig wall were. Two parapatric species of Philotrypesis, exhibiting strikingly different ovipositor lengths, were recorded. One species of Sycoscapter was also present, and it was restricted, like the shorter-ovipositor Philotrypesis, to the geographic zone where fig walls were thinner.

CONCLUSIONS: Previous work on fig wasps suggested that parapatric geographic ranges among congenerics were due to adaptation to variation in abiotic factors, complemented by interspecific competition. Our results show that parapatric ranges may also result from adaptation to variation in biotic factors. Within an insect community, differences among species in their response to geographic phenotypic variation of their host plant may result in geographically heterogeneous community structure. Such heterogeneity leads to heterogeneous interaction networks among sites. Our results support the hypothesis that plant geographic phenotypic variation can be a driver of diversification in associated insect communities, and can complement other diversification processes.}, } @article {pmid30180794, year = {2018}, author = {Ghattargi, VC and Gaikwad, MA and Meti, BS and Nimonkar, YS and Dixit, K and Prakash, O and Shouche, YS and Pawar, SP and Dhotre, DP}, title = {Comparative genome analysis reveals key genetic factors associated with probiotic property in Enterococcus faecium strains.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {652}, pmid = {30180794}, issn = {1471-2164}, support = {BT/Coord.II/01/03/2016//Department of Biotechnology , Ministry of Science and Technology/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/*genetics ; *Drug Resistance, Microbial ; Enterococcus faecium/drug effects/*genetics/isolation & purification ; Gastrointestinal Tract/microbiology ; *Genome, Bacterial ; Genomics ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; *Probiotics ; Virulence/*drug effects ; Virulence Factors ; }, abstract = {BACKGROUND: Enterococcus faecium though commensal in the human gut, few strains provide a beneficial effect to humans as probiotics while few are responsible for the nosocomial infection. Comparative genomics of E. faecium can decipher the genomic differences responsible for probiotic, pathogenic and non-pathogenic properties. In this study, we compared E. faecium strain 17OM39 with a marketed probiotic, non-pathogenic non-probiotic (NPNP) and pathogenic strains.

RESULTS: E. faecium 17OM39 was found to be closely related with marketed probiotic strain T110 based on core genome analysis. Strain 17OM39 was devoid of known vancomycin, tetracycline resistance and functional virulence genes. Moreover, E. faecium 17OM39 genome was found to be more stable due to the absence of frequently found transposable elements. Genes imparting beneficial functional properties were observed to be present in marketed probiotic T110 and 17OM39 strains. Genes associated with colonization and survival within gastrointestinal tract was also detected across all the strains.

CONCLUSIONS: Beyond shared genetic features; this study particularly identified genes that are responsible for imparting probiotic, non-pathogenic and pathogenic features to the strains of E. faecium. Higher genomic stability, absence of known virulence factors and antibiotic resistance genes and close genomic relatedness with marketed probiotics makes E. faecium 17OM39 a potential probiotic candidate. The work presented here demonstrates that comparative genome analyses can be applied to large numbers of genomes, to find potential probiotic candidates.}, } @article {pmid30180793, year = {2018}, author = {Wang, X and Zhang, L and Ji, H and Mo, X and Li, P and Wang, J and Dong, H}, title = {Hpa1 is a type III translocator in Xanthomonas oryzae pv. oryzae.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {105}, pmid = {30180793}, issn = {1471-2180}, abstract = {BACKGROUND: Pathogenic Gram-negative bacteria interact with their eukaryotic hosts by deploying the type III translocon to inject effector proteins into the cytosol of eukaryotic cells. The translocon compositions, the number and biochemical characteristics of type III translocators in animal-pathogenic bacteria have been well elucidated, but information is lacking for plant-pathogenic bacteria. With extensive studies on biological functions of the Hpa1 protein secreted by the type III secretion system in Xanthomonas oryzae pv. oryzae (Xoo), we show here that Hpa1 is a type III translocator based on measurements of two proteins categorized as transcription activator-like (TAL) effector.

RESULTS: Hpa1 was functionally associated with the TAL effector PthXo1 or AvrXa10 by genetic analysis of the wild-type Xoo strain and related mutants or recombinant strains. Inoculation experiments suggested that Hpa1 is required not only for the virulent role of PthXo1 in the susceptible rice variety Nipponbare, but also for the avirulent function of AvrXa10 on the resistant rice variety IRBB10. Hpa1 is unrelated to the secretion of PthXo1 and AvrXa10 out of bacterial cells. However, Hpa1 is critical for both TAL effectors to be translocated from bacterial cells into the cytosol of rice cells based on replicate experiments performed on the susceptible and resistant varieties, respectively. Hpa1-mediated translocation of PthXo1 is coincident with induced expression of rice SWEET11 gene, which is the regulatory target of PthXo1, resulting in the occurrence of the bacterial blight disease in the susceptible rice variety. By contrast, the immune hypersensitive response is induced in agreement with induced expression of rice Xa10 gene, which is the target of AvrXa10, only when AvrXa10 is translocated from bacteria into cells of the resistant rice variety. All the virulent or avirulent performances of the TAL effectors are nullified by directed mutation that removes the α-helix motif from the Hpa1 sequence.

CONCLUSIONS: The genetic and biochemical data demonstrate that Hap1 is a type III translocator at least for TAL effectors PthXo1 and AvrXa10. The effect of the directed mutation suggests that Hpa1 depends on its α-helical motif to fulfil the translocator function.}, } @article {pmid30180792, year = {2018}, author = {Olgun, G and Sahin, O and Tastan, O}, title = {Discovering lncRNA mediated sponge interactions in breast cancer molecular subtypes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {650}, pmid = {30180792}, issn = {1471-2164}, support = {214S364//TUBITAK/ ; }, mesh = {Breast Neoplasms/classification/*genetics/metabolism/pathology ; Carcinoma, Basal Cell/classification/*genetics/metabolism/pathology ; Computational Biology ; Female ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; MicroRNAs/*genetics ; Prognosis ; RNA, Long Noncoding/*genetics ; RNA, Messenger/*genetics ; Receptor, ErbB-2/*metabolism ; Survival Rate ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) can indirectly regulate mRNAs expression levels by sequestering microRNAs (miRNAs), and act as competing endogenous RNAs (ceRNAs) or as sponges. Previous studies identified lncRNA-mediated sponge interactions in various cancers including the breast cancer. However, breast cancer subtypes are quite distinct in terms of their molecular profiles; therefore, ceRNAs are expected to be subtype-specific as well.

RESULTS: To find lncRNA-mediated ceRNA interactions in breast cancer subtypes, we develop an integrative approach. We conduct partial correlation analysis and kernel independence tests on patient gene expression profiles and further refine the candidate interactions with miRNA target information. We find that although there are sponges common to multiple subtypes, there are also distinct subtype-specific interactions. Functional enrichment of mRNAs that participate in these interactions highlights distinct biological processes for different subtypes. Interestingly, some of the ceRNAs also reside in close proximity in the genome; for example, those involving HOX genes, HOTAIR, miR-196a-1 and miR-196a-2. We also discover subtype-specific sponge interactions with high prognostic potential. We found that patients differ significantly in their survival distributions if they are group based on the expression patterns of specific ceRNA interactions. However, it is not the case if the expression of individual RNAs participating in ceRNA is used.

CONCLUSION: These results can help shed light on subtype-specific mechanisms of breast cancer, and the methodology developed herein can help uncover sponges in other diseases.}, } @article {pmid30179878, year = {2018}, author = {Mary, N and Villagómez, DAF and Revay, T and Rezaei, S and Donaldson, B and Pinton, A and King, WA}, title = {Meiotic Synapsis and Gene Expression Altered by a Balanced Y-Autosome Reciprocal Translocation in an Azoospermic Pig.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {5}, pages = {}, doi = {10.1159/000491804}, pmid = {30179878}, issn = {1661-5433}, abstract = {Meiotic sex chromosome silencing (MSCS) has been argued as a prerequisite for normal meiotic cell division progression during the synaptic prophase I stage. Furthermore, irregular asynapsis of autosomal axes at meiosis may be encompassing the lack of transcriptional activity normally observed for the X and Y sex chromosomes. Therefore, any chromosomal rearrangement compromising the normal mechanism of MSCS and/or the contrary, the normal meiotic transcriptional activity of autosomal chromosomes, may be observed as a meiotic and concomitant spermatogenesis arrest. Previously, we have described a Y-autosome translocation t(Y;13)(p1.3;q3.3) in an azoospermic boar. Its chromosome synapsis behavior by synaptonemal complex immunostaining and FISH analyses is documented here. Histone γH2AX protein foci appeared to be located at unsynapsed chromosomal segments (e.g., X chromosome univalents or unpaired multivalent segments), although interestingly a high proportion of primary spermatocytes showed full paired synaptonemal complex-multivalent configurations which were devoid of a γH2AX focus signal, indicating meiotic chromosome silencing. RT-qPCR analysis of testicular expression showed downregulation of 3 SSC13 genes (MLH1, SOX2, UBE2B) and upregulation of SSCY genes (ZFY, SRY). The irregularity of the normal transcription pattern in case of these genes with proven roles in the testis is in agreement with the cytological observations and could contribute to the observed phenotype.}, } @article {pmid30179698, year = {2018}, author = {Luo, Z and Li, S and Hou, K and Ji, G}, title = {Spatial and seasonal bacterioplankton community dynamics in the main channel of the Middle Route of South-to-North Water Diversion Project.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.08.004}, pmid = {30179698}, issn = {1769-7123}, abstract = {In this study, the spatial and seasonal bacterioplankton community dynamics were investigated in the main channel of the Middle Route of the South-to-North Water Diversion Project (MRP) using Illumina HiSeq sequencing. Water samples were collected in spring and summer from south to north at eight water quality monitoring stations, respectively. The results showed that seasonal changes had a more pronounced effect on the bacterioplankton community compositions (BCCs) than spatial variation. The diversity analysis results indicated that samples of summer have more operational taxonomic units (OTUs), higher richness and diversity than those in spring. The main phyla, Proteobacteria, Actinobacteria, Bacteroidetes, Cyanobacteria and Chloroflexi, displayed significant differences (P < 0.05) between spring and summer in the main channel. The Redundancy analysis (RDA) targeting all samples indicated that specific conductivity (SPC), dissolved oxygen (DO), pH and temperature (T) might be key factors in driving BCCs, while trophic status showed no significant correlation (P > 0.05). The present study provides important insights into the potential ecological roles of specific taxa in the new artificial ecosystem and it offers reference for studies on ecosystem succession of other giant interbasin water diversion project in the world.}, } @article {pmid30179697, year = {2018}, author = {Aguirre, P and Guerrero, K and Sanchez-Rodriguez, A and Gentina, JC and Schippers, A}, title = {Making sticky cells: effect of galactose and ferrous iron on the attachment of Leptospirillum ferrooxidans to mineral surfaces.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {569-575}, doi = {10.1016/j.resmic.2018.08.005}, pmid = {30179697}, issn = {1769-7123}, mesh = {Bacteria/chemistry/growth & development/*metabolism ; Biopolymers/*chemistry/metabolism ; Culture Media/chemistry/metabolism ; Ferrous Compounds/*metabolism ; Galactose/*metabolism ; Minerals/*metabolism ; }, abstract = {The purpose of this study was to compare the efficacy of galactose and high initial ferrous iron concentrations as inducers for extracellular polymeric substances (EPS) production in planktonic cells of Leptospirillum ferrooxidans and to study cell attachment to a mineral surface in comparison to cells not exposed to such substances. L. ferrooxidans was successfully adapted to grow in a modified 9K medium at different concentrations of galactose (0.15, 0.25, 0.35%) and also at different initial ferrous iron concentrations (18, 27, 36 g/L), which are higher than 9K medium (9 g/L). The experiments were done in shake flasks using ferrous iron as energy source. A comparison of growth kinetics showed a decreasing of maximum specific growth rate of L. ferrooxidans with increasing concentrations of galactose and initial ferrous iron. The EPS content increased and the EPS chemical composition (relative abundance of carbohydrates, proteins and ferric iron) changed with increasing concentrations of galactose and initial ferrous iron. Results revealed that the increase of the bacterial adhesion rather depended on the chemical composition, i.e. relative abundance of the constituents of the EPS, than on the total amount of EPS. The EPS induced by galactose seemed to be "stickier" than the one induced by ferrous iron. Based on the results of this study it is proposed that galactose might enhance biooxidation processes which needs to be tested in future studies.}, } @article {pmid30179696, year = {2018}, author = {Liu, LZ and Nie, ZY and Yang, Y and Pan, X and Xia, X and Zhou, YH and Xia, JL and Zhang, LJ and Zhen, XJ and Yang, HY}, title = {In situ characterization of change in superficial organic components of thermoacidophilic archaeon Acidianus manzaensis YN-25.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {590-597}, doi = {10.1016/j.resmic.2018.08.003}, pmid = {30179696}, issn = {1769-7123}, mesh = {Acidianus/chemistry/*cytology/growth & development/*metabolism ; Biopolymers/chemistry/metabolism ; Ferrous Compounds/chemistry/*metabolism ; Hot Temperature ; Microscopy, Atomic Force ; X-Ray Absorption Spectroscopy ; }, abstract = {For the first time, synchrotron radiation (SR) -based carbon K-edge X-ray absorption near edge structure (XANES) spectroscopy in-situ characterization was conducted to evaluate the evolution of superficial (about 10 nm) organic components of extracellular polymeric substances (EPS) of thermoacidophilic archaeon Acidianus manzaensis YN-25 acclimated with different energy substrates (FeS2, CuFeS2, S0, FeSO4). The atomic force microscopy (AFM) morphology scanning showed that the strain acclimated with different energy substrates varied a lot in EPS amount. XANES results showed clear associations between the energy substrates and the changes in organic composition in terms of typical function groups (CO, CO and CN). The chalcopyrite- and pyrite-acclimated cells contained higher proportion of proteins but less proportion of polysaccharides than the S0-acclimated cells. The FeSO4-acclimated cells contained the highest proportion of proteins, while the S0-acclimated cells contained more lipids and polysaccharides. The results of linear-combination and peak fitting of the K-edge XANES for the extracellular superficial organic component C is consistent with the trend in comparison with the results of FTIR and spectrophotometric determination, but there are significant differences in the values. These differences are caused by the inconsistencies of measurement depth between XANES and the latter two characterization methods.}, } @article {pmid30179592, year = {2018}, author = {Hartman, BH and Bӧscke, R and Ellwanger, DC and Keymeulen, S and Scheibinger, M and Heller, S}, title = {Fbxo2VHC mouse and embryonic stem cell reporter lines delineate in vitro-generated inner ear sensory epithelia cells and enable otic lineage selection and Cre-recombination.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {64-77}, doi = {10.1016/j.ydbio.2018.08.013}, pmid = {30179592}, issn = {1095-564X}, support = {R01 DC015201/DC/NIDCD NIH HHS/United States ; F32 DC013210/DC/NIDCD NIH HHS/United States ; P30 DC010363/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle Proteins/*genetics/*metabolism ; Cell Lineage ; Cochlea/embryology/metabolism ; Ear, Inner/*embryology/metabolism ; Embryonic Stem Cells/physiology ; Epithelium/metabolism ; F-Box Proteins/*genetics/*metabolism ; Ganglia, Parasympathetic ; Genetic Engineering/methods ; Humans ; Immunohistochemistry/methods ; Integrases ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins/*genetics/*metabolism ; Tamoxifen ; }, abstract = {While the mouse has been a productive model for inner ear studies, a lack of highly specific genes and tools has presented challenges. The absence of definitive otic lineage markers and tools is limiting in vitro studies of otic development, where innate cellular heterogeneity and disorganization increase the reliance on lineage-specific markers. To address this challenge in mice and embryonic stem (ES) cells, we targeted the lineage-specific otic gene Fbxo2 with a multicistronic reporter cassette (Venus/Hygro/CreER = VHC). In otic organoids derived from ES cells, Fbxo2VHC specifically delineates otic progenitors and inner ear sensory epithelia. In mice, Venus expression and CreER activity reveal a cochlear developmental gradient, label the prosensory lineage, show enrichment in a subset of type I vestibular hair cells, and expose strong expression in adult cerebellar granule cells. We provide a toolbox of multiple spectrally distinct reporter combinations for studies that require use of fluorescent reporters, hygromycin selection, and conditional Cre-mediated recombination.}, } @article {pmid30179152, year = {2018}, author = {Braune, A and Blaut, M}, title = {Catenibacillus scindens gen. nov., sp. nov., a C-deglycosylating human intestinal representative of the Lachnospiraceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3356-3361}, doi = {10.1099/ijsem.0.003001}, pmid = {30179152}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Clostridiales/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fermentation ; Germany ; Humans ; Intestines/*microbiology ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {An anaerobic Gram-stain-positive, non-spore-forming and non-motile bacterium isolated from the human gut, designated CG19-1T, capable of cleaving aromatic C-glucosides was characterized using a polyphasic taxonomic approach. Major fermentation products of this asaccharolytic organism were acetate and butyrate when grown on a complex medium. Growth of strain CG19-1T was stimulated by glucose or pyruvate. Growth inhibition was observed in the presence of several phenolic acids including ferulic acid, which nevertheless was reduced to dihydroferulic acid. Strain CG19-1T contained peptidoglycan type A4β l-Orn-d-Asp. The major cellular fatty acids were C16 : 0 and C18 : 1ω9c. The genomic DNA G+C content was 47.1 mol%. Based on its 16S rRNA gene sequence, strain CG19-1T is a member of the Lachnospiraceae. However, sequence identity to other Lachnospiraceae species with validly published names is approximately 93.0 % with Frisingicoccus caecimuris being the most closely related species according to phylogenetic analysis. Based on these findings, it is proposed to create a novel genus, Catenibacillus, and a novel species, Catenibacillus scindens, with the type strain CG19-1T (=DSM 106146T=CCUG 71490T).}, } @article {pmid30179151, year = {2018}, author = {Huang, H and Liu, M and Zhong, W and Mo, K and Zhu, J and Zou, X and Hu, Y and Bao, S}, title = {Nonomuraea mangrovi sp. nov., an actinomycete isolated from mangrove soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3144-3148}, doi = {10.1099/ijsem.0.002954}, pmid = {30179151}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhizophoraceae/*microbiology ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A novel aerobic actinomycete, designated HA15826T, was isolated from a mangrove soil sample collected in Sanya, China. Scanning electron microscopy revealed that the isolate produced straight to slightly flexural spore chains with rough cylindrical spores. Chemotaxonomic tests showed that the cell wall contained meso-diaminopimelic acid and the major fatty acids were iso-C16 : 0, 10-methyl-C17 : 0, C17 : 1ω8c and C16 : 0. 16S rRNA gene sequence similarity analysis showed that strain HA15826T belonged to the genus Nonomuraea, being most closely related to Nonomuraea dietziae DSM 44320T (98.7 %), Nonomuraea candida HMC10T (98.4 %), Nonomuraea africana IFO 14745T (98.4 %), Nonomuraea roseola IFO 14685T (98.2 %) and Nonomuraea recticatena IFO 14525T (98.1 %). The DNA G+C content of the type strain is 73.2 %. DNA-DNA relatedness and comparative analyses of physiological, biochemical and chemotaxonomic data allowed genotypic and phenotypic differentiation of strain HA15826T from the closely related species. Thus, strain HA15826T should be classified as a novel species of the genus Nonomuraea, for which the name Nonomuraeamangrovi sp. nov. is proposed. The type strain is HA15826T (=CGMCC 4.7425T=DSM 105694T).}, } @article {pmid30178526, year = {2018}, author = {Berson, JD and Simmons, LW}, title = {A costly chemical trait: phenotypic condition dependence of cuticular hydrocarbons in a dung beetle.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1772-1781}, doi = {10.1111/jeb.13371}, pmid = {30178526}, issn = {1420-9101}, support = {//Australian Government Research Training Program Scholarship/ ; //ARC Discovery Project/ ; }, abstract = {Chemical traits are increasingly recognized as important cues used in mate choice. For example, the cuticular hydrocarbons (CHCs) of insects have been shown to influence mating success in a range of taxa. Less is known, however, about how CHCs are expressed in proportion to an individual's condition, and consequently whether CHCs can function as condition-dependent signals of quality. We investigated this question using the dung beetle, Onthophagus taurus. CHCs are subject to sexual selection in this species through mate choice. A dietary manipulation revealed condition dependence of CHC expression for both sexes: dietary restriction decreased overall CHC production and altered the composition of CHCs. Furthermore, CHC production was associated with a measure of condition in beetles fed a limited diet but not those fed ad libitum. These results implicate a resource cost to CHC production that is likely to result in trade-offs with other fitness components in this species, as these respond similarly to a dietary restriction. The CHC profiles showed sexual dimorphism: males produced more CHCs and the sexes differed in the blend of compounds they produced. There was evidence for a male dimorphism in the CHC profile, in line with the presence of the alternative reproductive tactics (minor sneaks and major fighters) in this species. However, rather than mimicking a female CHC profile, minor males differed more from females than major males. Our results suggest that CHCs are a costly trait in O. taurus that has the potential to act as a condition-dependent signal of quality.}, } @article {pmid30178389, year = {2018}, author = {Zupkovitz, G and Kabiljo, J and Martin, D and Laffer, S and Schöfer, C and Pusch, O}, title = {Phylogenetic analysis and expression profiling of the Klotho gene family in the short-lived African killifish Nothobranchius furzeri.}, journal = {Development genes and evolution}, volume = {228}, number = {6}, pages = {255-265}, pmid = {30178389}, issn = {1432-041X}, support = {P30642//FWF/ ; }, abstract = {Members of the Klotho gene family have been identified as modulators of the aging process. Deletion of αklotho in the mouse results in a syndrome resembling rapid human aging. Conversely, overexpression of αklotho extends mammalian lifespan. Here, we identify klotho orthologs in the vertebrate aging model Nothobranchius furzeri and provide a detailed spatio-temporal expression profile of both paralogs, α and βklotho, from embryogenesis until old age spanning the entire life cycle of the organism. Specifically, we observe low levels of expression of both paralogs during embryogenesis followed by a significant transcriptional induction as development proceeds. In adult killifish, αklotho is predominantly expressed in the liver, the kidney, and the developing pharyngeal teeth. Particularly high levels of αKlotho protein were identified in the kidney tubules, closely resembling mammalian expression patterns. Prominent βklotho expression was detected in the killifish intestine and liver. Overall, qRT-PCR analysis of Klotho members as a function of age revealed steady transcript levels, except for βklotho expression in the liver which was significantly downregulated with age. This spatio-temporal expression profiling may serve as a useful starting point to further investigate the distinct physiological roles of Klotho members during the aging process.}, } @article {pmid30178099, year = {2018}, author = {Mumtaz, R and Bashir, S and Numan, M and Shinwari, ZK and Ali, M}, title = {Pigments from Soil Bacteria and Their Therapeutic Properties: A Mini Review.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1557-2}, pmid = {30178099}, issn = {1432-0991}, abstract = {Advancement in research on dyes obtained from natural sources e.g., plants, animals, insects and micro-organisms is widening the application of natural dyes in various fields. The natural dyes substituted their synthetic analogs at the beginning of twentieth century due to their improved quality, value, ease of production, ease of dyeing and some other factors. This era of dominance ended soon when toxic effects of synthetic dyes were reported. In the last few decades, pigments from micro-organisms especially soil derived bacteria is replacing dyes from other natural sources because of the increasing demand for safe, non-toxic, and biodegradable natural product. Apart from application in agriculture practices, cosmetics, textile, food and paper industries, bacterial pigments have additional biological activities e.g., anti-tumor, anti-fungal, anti-bacterial, immunosuppressive anti-viral, and many more which make them a potential candidate for pharmaceutical industry. Optimization of culture conditions and fermentation medium is the key strategies for large scale production of these natural dyes. An effort has been done to give an overview of pigments obtained from bacteria of soil origin, their dominance over dyes from other sources (natural and synthetic) and applications in the medical world in the underlying study.}, } @article {pmid30177863, year = {2018}, author = {Maguire, LH and Handelman, SK and Du, X and Chen, Y and Pers, TH and Speliotes, EK}, title = {Genome-wide association analyses identify 39 new susceptibility loci for diverticular disease.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1359-1365}, pmid = {30177863}, issn = {1546-1718}, support = {R01 DK106621/DK/NIDDK NIH HHS/United States ; R01 DK107904/DK/NIDDK NIH HHS/United States ; }, abstract = {Diverticular disease is common and has a high morbidity. Treatments are limited owing to the poor understanding of its pathophysiology. Here, to elucidate its etiology, we performed a genome-wide association study of diverticular disease (27,444 cases; 382,284 controls) from the UK Biobank and tested for replication in the Michigan Genomics Initiative (2,572 cases; 28,649 controls). We identified 42 loci associated with diverticular disease; 39 of these loci are novel. Using data-driven expression-prioritized integration for complex traits (DEPICT), we show that genes in these associated regions are significantly enriched for expression in mesenchymal stem cells and multiple connective tissue cell types and are co-expressed with genes that have a role in vascular and mesenchymal biology. Genes in these associated loci have roles in immunity, extracellular matrix biology, cell adhesion, membrane transport and intestinal motility. Phenome-wide association analysis of the 42 variants shows a common etiology of diverticular disease with obesity and hernia. These analyses shed light on the genomic landscape of diverticular disease.}, } @article {pmid30177862, year = {2018}, author = {Reshef, YA and Finucane, HK and Kelley, DR and Gusev, A and Kotliar, D and Ulirsch, JC and Hormozdiari, F and Nasser, J and O'Connor, L and van de Geijn, B and Loh, PR and Grossman, SR and Bhatia, G and Gazal, S and Palamara, PF and Pinello, L and Patterson, N and Adams, RP and Price, AL}, title = {Detecting genome-wide directional effects of transcription factor binding on polygenic disease risk.}, journal = {Nature genetics}, volume = {50}, number = {10}, pages = {1483-1493}, pmid = {30177862}, issn = {1546-1718}, support = {S10 RR028832/RR/NCRR NIH HHS/United States ; P50 HD028138/HD/NICHD NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; T32 DK110919/DK/NIDDK NIH HHS/United States ; R00 HG008399/HG/NHGRI NIH HHS/United States ; U01 HG009379/HG/NHGRI NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; R01 MH101244/MH/NIMH NIH HHS/United States ; R01 MH109978/MH/NIMH NIH HHS/United States ; }, abstract = {Biological interpretation of genome-wide association study data frequently involves assessing whether SNPs linked to a biological process, for example, binding of a transcription factor, show unsigned enrichment for disease signal. However, signed annotations quantifying whether each SNP allele promotes or hinders the biological process can enable stronger statements about disease mechanism. We introduce a method, signed linkage disequilibrium profile regression, for detecting genome-wide directional effects of signed functional annotations on disease risk. We validate the method via simulations and application to molecular quantitative trait loci in blood, recovering known transcriptional regulators. We apply the method to expression quantitative trait loci in 48 Genotype-Tissue Expression tissues, identifying 651 transcription factor-tissue associations including 30 with robust evidence of tissue specificity. We apply the method to 46 diseases and complex traits (average n = 290 K), identifying 77 annotation-trait associations representing 12 independent transcription factor-trait associations, and characterize the underlying transcriptional programs using gene-set enrichment analyses. Our results implicate new causal disease genes and new disease mechanisms.}, } @article {pmid30177828, year = {2018}, author = {Scaturro, P and Stukalov, A and Haas, DA and Cortese, M and Draganova, K and Płaszczyca, A and Bartenschlager, R and Götz, M and Pichlmair, A}, title = {An orthogonal proteomic survey uncovers novel Zika virus host factors.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {253-257}, doi = {10.1038/s41586-018-0484-5}, pmid = {30177828}, issn = {1476-4687}, abstract = {Zika virus (ZIKV) has recently emerged as a global health concern owing to its widespread diffusion and its association with severe neurological symptoms and microcephaly in newborns1. However, the molecular mechanisms that are responsible for the pathogenicity of ZIKV remain largely unknown. Here we use human neural progenitor cells and the neuronal cell line SK-N-BE2 in an integrated proteomics approach to characterize the cellular responses to viral infection at the proteome and phosphoproteome level, and use affinity proteomics to identify cellular targets of ZIKV proteins. Using this approach, we identify 386 ZIKV-interacting proteins, ZIKV-specific and pan-flaviviral activities as well as host factors with known functions in neuronal development, retinal defects and infertility. Moreover, our analysis identified 1,216 phosphorylation sites that are specifically up- or downregulated after ZIKV infection, indicating profound modulation of fundamental signalling pathways such as AKT, MAPK-ERK and ATM-ATR and thereby providing mechanistic insights into the proliferation arrest elicited by ZIKV infection. Functionally, our integrative study identifies ZIKV host-dependency factors and provides a comprehensive framework for a system-level understanding of ZIKV-induced perturbations at the levels of proteins and cellular pathways.}, } @article {pmid30177827, year = {2018}, author = {Perraki, A and DeFalco, TA and Derbyshire, P and Avila, J and Séré, D and Sklenar, J and Qi, X and Stransfeld, L and Schwessinger, B and Kadota, Y and Macho, AP and Jiang, S and Couto, D and Torii, KU and Menke, FLH and Zipfel, C}, title = {Phosphocode-dependent functional dichotomy of a common co-receptor in plant signalling.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {248-252}, pmid = {30177827}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Multicellular organisms use cell-surface receptor kinases to sense and process extracellular signals. Many plant receptor kinases are activated by the formation of ligand-induced complexes with shape-complementary co-receptors1. The best-characterized co-receptor is BRASSINOSTEROID INSENSITIVE 1-ASSOCIATED KINASE 1 (BAK1), which associates with numerous leucine-rich repeat receptor kinases (LRR-RKs) to control immunity, growth and development2. Here we report key regulatory events that control the function of BAK1 and, more generally, LRR-RKs. Through a combination of phosphoproteomics and targeted mutagenesis, we identified conserved phosphosites that are required for the immune function of BAK1 in Arabidopsis thaliana. Notably, these phosphosites are not required for BAK1-dependent brassinosteroid-regulated growth. In addition to revealing a critical role for the phosphorylation of the BAK1 C-terminal tail, we identified a conserved tyrosine phosphosite that may be required for the function of the majority of Arabidopsis LRR-RKs, and which separates them into two distinct functional classes based on the presence or absence of this tyrosine. Our results suggest a phosphocode-based dichotomy of BAK1 function in plant signalling, and provide insights into receptor kinase activation that have broad implications for our understanding of how plants respond to their changing environment.}, } @article {pmid30177826, year = {2018}, author = {Makohon-Moore, AP and Matsukuma, K and Zhang, M and Reiter, JG and Gerold, JM and Jiao, Y and Sikkema, L and Attiyeh, MA and Yachida, S and Sandone, C and Hruban, RH and Klimstra, DS and Papadopoulos, N and Nowak, MA and Kinzler, KW and Vogelstein, B and Iacobuzio-Donahue, CA}, title = {Precancerous neoplastic cells can move through the pancreatic ductal system.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {201-205}, doi = {10.1038/s41586-018-0481-8}, pmid = {30177826}, issn = {1476-4687}, support = {T32 CA160001/CA/NCI NIH HHS/United States ; T32 CA067751/CA/NCI NIH HHS/United States ; F31 CA180682/CA/NCI NIH HHS/United States ; P50 CA062924/CA/NCI NIH HHS/United States ; 5T32 CA067751-13/CN/NCI NIH HHS/United States ; 2T32 CA160001-06//NCI/International ; }, abstract = {Most adult carcinomas develop from noninvasive precursor lesions, a progression that is supported by genetic analysis. However, the evolutionary and genetic relationships among co-existing lesions are unclear. Here we analysed the somatic variants of pancreatic cancers and precursor lesions sampled from distinct regions of the same pancreas. After inferring evolutionary relationships, we found that the ancestral cell had initiated and clonally expanded to form one or more lesions, and that subsequent driver gene mutations eventually led to invasive pancreatic cancer. We estimate that this multi-step progression generally spans many years. These new data reframe the step-wise progression model of pancreatic cancer by illustrating that independent, high-grade pancreatic precursor lesions observed in a single pancreas often represent a single neoplasm that has colonized the ductal system, accumulating spatial and genetic divergence over time.}, } @article {pmid30177825, year = {2018}, author = {Thompson, D and Zhu, L and Mittapally, R and Sadat, S and Xing, Z and McArdle, P and Qazilbash, MM and Reddy, P and Meyhofer, E}, title = {Hundred-fold enhancement in far-field radiative heat transfer over the blackbody limit.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {216-221}, doi = {10.1038/s41586-018-0480-9}, pmid = {30177825}, issn = {1476-4687}, abstract = {Radiative heat transfer (RHT) has a central role in entropy generation and energy transfer at length scales ranging from nanometres to light years1. The blackbody limit2, as established in Max Planck's theory of RHT, provides a convenient metric for quantifying rates of RHT because it represents the maximum possible rate of RHT between macroscopic objects in the far field-that is, at separations greater than Wien's wavelength3. Recent experimental work has verified the feasibility of overcoming the blackbody limit in the near field4-7, but heat-transfer rates exceeding the blackbody limit have not previously been demonstrated in the far field. Here we use custom-fabricated calorimetric nanostructures with embedded thermometers to show that RHT between planar membranes with sub-wavelength dimensions can exceed the blackbody limit in the far field by more than two orders of magnitude. The heat-transfer rates that we observe are in good agreement with calculations based on fluctuational electrodynamics. These findings may be directly relevant to various fields, such as energy conversion, atmospheric sciences and astrophysics, in which RHT is important.}, } @article {pmid30177805, year = {2018}, author = {Foffa, D and Young, MT and Stubbs, TL and Dexter, KG and Brusatte, SL}, title = {The long-term ecology and evolution of marine reptiles in a Jurassic seaway.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1548-1555}, doi = {10.1038/s41559-018-0656-6}, pmid = {30177805}, issn = {2397-334X}, abstract = {Marine reptiles flourished in the Mesozoic oceans, filling ecological roles today dominated by crocodylians, large fish, sharks and cetaceans. Many groups of these reptiles coexisted for over 50 million years (Myr), through major environmental changes. However, little is known about how the structure of their ecosystems or their ecologies changed over millions of years. We use the most common marine reptile fossils-teeth-to establish a quantitative system that assigns species to dietary guilds and then track the evolution of these guilds over the roughly 18-million-year history of a single seaway, the Jurassic Sub-Boreal Seaway of the United Kingdom. Groups did not significantly overlap in guild space, indicating that dietary niche partitioning enabled many species to live together. Although a highly diverse fauna was present throughout the history of the seaway, fish and squid eaters with piercing teeth declined over time while hard-object and large-prey specialists diversified, in concert with rising sea levels. High niche partitioning and spatial variation in dietary ecology related to sea depth also characterize modern marine tetrapod faunas, indicating a conserved ecological structure of the world's oceans that has persisted for over 150 Myr.}, } @article {pmid30177804, year = {2018}, author = {Cross, W and Kovac, M and Mustonen, V and Temko, D and Davis, H and Baker, AM and Biswas, S and Arnold, R and Chegwidden, L and Gatenbee, C and Anderson, AR and Koelzer, VH and Martinez, P and Jiang, X and Domingo, E and Woodcock, DJ and Feng, Y and Kovacova, M and Maughan, T and , and Jansen, M and Rodriguez-Justo, M and Ashraf, S and Guy, R and Cunningham, C and East, JE and Wedge, DC and Wang, LM and Palles, C and Heinimann, K and Sottoriva, A and Leedham, SJ and Graham, TA and Tomlinson, IPM}, title = {The evolutionary landscape of colorectal tumorigenesis.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1661-1672}, pmid = {30177804}, issn = {2397-334X}, support = {//Wellcome Trust/United Kingdom ; MR/K000063/1//Medical Research Council/United Kingdom ; }, abstract = {The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, we investigate the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations-considered to be functionally important in the carcinogenic process-that have not swept to fixation, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas by widespread aneusomies that are usually clonal and often accrue in a 'punctuated' fashion. We conclude that adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilizing selection.}, } @article {pmid30177803, year = {2018}, author = {Metz, MC and Emlen, DJ and Stahler, DR and MacNulty, DR and Smith, DW and Hebblewhite, M}, title = {Predation shapes the evolutionary traits of cervid weapons.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1619-1625}, doi = {10.1038/s41559-018-0657-5}, pmid = {30177803}, issn = {2397-334X}, abstract = {Sexually selected weapons evolved to maximize the individual reproductive success of males in many polygynous breeding species. Many weapons are also retained outside of reproductive periods for secondary reasons, but the importance of these secondary functions is poorly understood. Here we leveraged a unique opportunity from the predator-prey system in northern Yellowstone National Park, WY, USA to evaluate whether predation by a widespread, coursing predator (wolves) has influenced a specific weapon trait (antler retention time) in their primary cervid prey (elk). Male elk face a trade-off: individuals casting antlers early begin regrowth before other males, resulting in relatively larger antlers the following year, and thus greater reproductive success, as indicated by research with red deer. We show, however, that male elk that cast their antlers early are preferentially hunted and killed by wolves, despite early casters being in better nutritional condition than antlered individuals. Our results run counter to classic expectations of coursing predators preferring poorer-conditioned individuals, and in so doing, reveal an important secondary function for an exaggerated sexually selected weapon-predatory deterrence. We suggest this secondary function played a key evolutionary role in elk; uniquely among North American cervids, they retain their antlers long after they fulfil their primary role in reproduction.}, } @article {pmid30177802, year = {2018}, author = {Harrison, AL and Costa, DP and Winship, AJ and Benson, SR and Bograd, SJ and Antolos, M and Carlisle, AB and Dewar, H and Dutton, PH and Jorgensen, SJ and Kohin, S and Mate, BR and Robinson, PW and Schaefer, KM and Shaffer, SA and Shillinger, GL and Simmons, SE and Weng, KC and Gjerde, KM and Block, BA}, title = {The political biogeography of migratory marine predators.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1571-1578}, doi = {10.1038/s41559-018-0646-8}, pmid = {30177802}, issn = {2397-334X}, abstract = {During their migrations, marine predators experience varying levels of protection and face many threats as they travel through multiple countries' jurisdictions and across ocean basins. Some populations are declining rapidly. Contributing to such declines is a failure of some international agreements to ensure effective cooperation by the stakeholders responsible for managing species throughout their ranges, including in the high seas, a global commons. Here we use biologging data from marine predators to provide quantitative measures with great potential to inform local, national and international management efforts in the Pacific Ocean. We synthesized a large tracking data set to show how the movements and migratory phenology of 1,648 individuals representing 14 species-from leatherback turtles to white sharks-relate to the geopolitical boundaries of the Pacific Ocean throughout species' annual cycles. Cumulatively, these species visited 86% of Pacific Ocean countries and some spent three-quarters of their annual cycles in the high seas. With our results, we offer answers to questions posed when designing international strategies for managing migratory species.}, } @article {pmid30177801, year = {2018}, author = {Snijders, L and Kurvers, RHJM and Krause, S and Ramnarine, IW and Krause, J}, title = {Individual- and population-level drivers of consistent foraging success across environments.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1610-1618}, doi = {10.1038/s41559-018-0658-4}, pmid = {30177801}, issn = {2397-334X}, abstract = {Individual foraging is under strong natural selection. Yet, whether individuals differ consistently in their foraging success across environments, and which individual- and population-level traits might drive such differences, is largely unknown. We addressed this question in a field experiment, conducting over 1,100 foraging trials with subpopulations of guppies, Poecilia reticulata, translocated across environments in the wild. We show that individuals consistently differed in reaching and acquiring food resources, but not control 'resources', across environments. Social individuals reached and acquired more food resources than less-social ones and males reached more food resources than females. Yet, overall, individuals were more likely to join females at resources than males, which might explain why individuals in subpopulations with relatively more females reached and acquired, on average, more food resources. Our results provide rare evidence for individual differences in foraging success across environments, driven by individual- and population-level (sex ratio) traits.}, } @article {pmid30177800, year = {2018}, author = {York, A}, title = {Next-generation bacterial taxonomy.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {583}, doi = {10.1038/s41579-018-0083-3}, pmid = {30177800}, issn = {1740-1534}, } @article {pmid30177799, year = {2018}, author = {York, A}, title = {Slipping through the NET.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {583}, doi = {10.1038/s41579-018-0084-2}, pmid = {30177799}, issn = {1740-1534}, } @article {pmid30177798, year = {2018}, author = {York, A}, title = {Pick of the crop microbiome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {583}, doi = {10.1038/s41579-018-0082-4}, pmid = {30177798}, issn = {1740-1534}, } @article {pmid30177797, year = {2018}, author = {York, A}, title = {Channeling the vacuole.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {581}, doi = {10.1038/s41579-018-0081-5}, pmid = {30177797}, issn = {1740-1534}, } @article {pmid30177748, year = {2018}, author = {}, title = {The landmark lectures of physicist Erwin Schrödinger helped to change attitudes in biology.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {6}, doi = {10.1038/d41586-018-06166-x}, pmid = {30177748}, issn = {1476-4687}, mesh = {Attitude ; *Biology ; *Physics ; }, } @article {pmid30177744, year = {2018}, author = {Tromp, AT and Van Gent, M and Abrial, P and Martin, A and Jansen, JP and De Haas, CJC and Van Kessel, KPM and Bardoel, BW and Kruse, E and Bourdonnay, E and Boettcher, M and McManus, MT and Day, CJ and Jennings, MP and Lina, G and Vandenesch, F and Van Strijp, JAG and Lebbink, RJ and Haas, PA and Henry, T and Spaan, AN}, title = {Publisher Correction: Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1187}, doi = {10.1038/s41564-018-0247-y}, pmid = {30177744}, issn = {2058-5276}, abstract = {In the version of this Article originally published, the name of author Robert Jan Lebbink was coded wrongly, resulting in it being incorrect when exported to citation databases. This has now been corrected, though no visible changes will be apparent.}, } @article {pmid30177743, year = {2018}, author = {Kent, RS and Modrzynska, KK and Cameron, R and Philip, N and Billker, O and Waters, AP}, title = {Inducible developmental reprogramming redefines commitment to sexual development in the malaria parasite Plasmodium berghei.}, journal = {Nature microbiology}, volume = {3}, number = {11}, pages = {1206-1213}, doi = {10.1038/s41564-018-0223-6}, pmid = {30177743}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {During malaria infection, Plasmodium spp. parasites cyclically invade red blood cells and can follow two different developmental pathways. They can either replicate asexually to sustain the infection, or differentiate into gametocytes, the sexual stage that can be taken up by mosquitoes, ultimately leading to disease transmission. Despite its importance for malaria control, the process of gametocytogenesis remains poorly understood, partially due to the difficulty of generating high numbers of sexually committed parasites in laboratory conditions1. Recently, an apicomplexa-specific transcription factor (AP2-G) was identified as necessary for gametocyte production in multiple Plasmodium species2,3, and suggested to be an epigenetically regulated master switch that initiates gametocytogenesis4,5. Here we show that in a rodent malaria parasite, Plasmodium berghei, conditional overexpression of AP2-G can be used to synchronously convert the great majority of the population into fertile gametocytes. This discovery allowed us to redefine the time frame of sexual commitment, identify a number of putative AP2-G targets and chart the sequence of transcriptional changes through gametocyte development, including the observation that gender-specific transcription occurred within 6 h of induction. These data provide entry points for further detailed characterization of the key process required for malaria transmission.}, } @article {pmid30177742, year = {2018}, author = {Quentin, D and Ahmad, S and Shanthamoorthy, P and Mougous, JD and Whitney, JC and Raunser, S}, title = {Mechanism of loading and translocation of type VI secretion system effector Tse6.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1142-1152}, doi = {10.1038/s41564-018-0238-z}, pmid = {30177742}, issn = {2058-5276}, abstract = {The type VI secretion system (T6SS) primarily functions to mediate antagonistic interactions between contacting bacterial cells, but also mediates interactions with eukaryotic hosts. This molecular machine secretes antibacterial effector proteins by undergoing cycles of extension and contraction; however, how effectors are loaded into the T6SS and subsequently delivered to target bacteria remains poorly understood. Here, using electron cryomicroscopy, we analysed the structures of the Pseudomonas aeruginosa effector Tse6 loaded onto the T6SS spike protein VgrG1 in solution and embedded in lipid nanodiscs. In the absence of membranes, Tse6 stability requires the chaperone EagT6, two dimers of which interact with the hydrophobic transmembrane domains of Tse6. EagT6 is not directly involved in Tse6 delivery but is crucial for its loading onto VgrG1. VgrG1-loaded Tse6 spontaneously enters membranes and its toxin domain translocates across a lipid bilayer, indicating that effector delivery by the T6SS does not require puncturing of the target cell inner membrane by VgrG1. Eag chaperone family members from diverse Proteobacteria are often encoded adjacent to putative toxins with predicted transmembrane domains and we therefore anticipate that our findings will be generalizable to numerous T6SS-exported membrane-associated effectors.}, } @article {pmid30177741, year = {2018}, author = {Beckert, B and Turk, M and Czech, A and Berninghausen, O and Beckmann, R and Ignatova, Z and Plitzko, JM and Wilson, DN}, title = {Structure of a hibernating 100S ribosome reveals an inactive conformation of the ribosomal protein S1.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1115-1121}, doi = {10.1038/s41564-018-0237-0}, pmid = {30177741}, issn = {2058-5276}, abstract = {To survive under conditions of stress, such as nutrient deprivation, bacterial 70S ribosomes dimerize to form hibernating 100S particles1. In γ-proteobacteria, such as Escherichia coli, 100S formation requires the ribosome modulation factor (RMF) and the hibernation promoting factor (HPF)2-4. Here we present single-particle cryo-electron microscopy structures of hibernating 70S and 100S particles isolated from stationary-phase E. coli cells at 3.0 Å and 7.9 Å resolution, respectively. The structures reveal the binding sites for HPF and RMF as well as the unexpected presence of deacylated E-site transfer RNA and ribosomal protein bS1. HPF interacts with the anticodon-stem-loop of the E-tRNA and occludes the binding site for the messenger RNA as well as A- and P-site tRNAs. RMF facilitates stabilization of a compact conformation of bS1, which together sequester the anti-Shine-Dalgarno sequence of the 16S ribosomal RNA (rRNA), thereby inhibiting translation initiation. At the dimerization interface, the C-terminus of uS2 probes the mRNA entrance channel of the symmetry-related particle, thus suggesting that dimerization inactivates ribosomes by blocking the binding of mRNA within the channel. The back-to-back E. coli 100S arrangement is distinct from 100S particles observed previously in Gram-positive bacteria5-8, and reveals a unique role for bS1 in translation regulation.}, } @article {pmid30177740, year = {2018}, author = {Lee, JYH and Monk, IR and Gonçalves da Silva, A and Seemann, T and Chua, KYL and Kearns, A and Hill, R and Woodford, N and Bartels, MD and Strommenger, B and Laurent, F and Dodémont, M and Deplano, A and Patel, R and Larsen, AR and Korman, TM and Stinear, TP and Howden, BP}, title = {Global spread of three multidrug-resistant lineages of Staphylococcus epidermidis.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1175-1185}, doi = {10.1038/s41564-018-0230-7}, pmid = {30177740}, issn = {2058-5276}, abstract = {Staphylococcus epidermidis is a conspicuous member of the human microbiome, widely present on healthy skin. Here we show that S. epidermidis has also evolved to become a formidable nosocomial pathogen. Using genomics, we reveal that three multidrug-resistant, hospital-adapted lineages of S. epidermidis (two ST2 and one ST23) have emerged in recent decades and spread globally. These lineages are resistant to rifampicin through acquisition of specific rpoB mutations that have become fixed in the populations. Analysis of isolates from 96 institutions in 24 countries identified dual D471E and I527M RpoB substitutions to be the most common cause of rifampicin resistance in S. epidermidis, accounting for 86.6% of mutations. Furthermore, we reveal that the D471E and I527M combination occurs almost exclusively in isolates from the ST2 and ST23 lineages. By breaching lineage-specific DNA methylation restriction modification barriers and then performing site-specific mutagenesis, we show that these rpoB mutations not only confer rifampicin resistance, but also reduce susceptibility to the last-line glycopeptide antibiotics, vancomycin and teicoplanin. Our study has uncovered the previously unrecognized international spread of a near pan-drug-resistant opportunistic pathogen, identifiable by a rifampicin-resistant phenotype. It is possible that hospital practices, such as antibiotic monotherapy utilizing rifampicin-impregnated medical devices, have driven the evolution of this organism, once trivialized as a contaminant, towards potentially incurable infections.}, } @article {pmid30177466, year = {2018}, author = {Inclan-Rico, JM and Siracusa, MC}, title = {First Responders: Innate Immunity to Helminths.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {861-880}, pmid = {30177466}, issn = {1471-5007}, support = {R01 AI123224/AI/NIAID NIH HHS/United States ; R01 AI131634/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Helminthiasis/*immunology ; Helminths/*immunology ; Host-Parasite Interactions/*immunology ; Humans ; *Immunity, Innate ; }, abstract = {Helminth infections represent a significant public health concern resulting in devastating morbidity and economic consequences across the globe. Helminths migrate through mucosal sites causing tissue damage and the induction of type 2 immune responses. Antihelminth protection relies on the mobilization and activation of multiple immune cells, including type 2 innate lymphocytes (ILC2s), basophils, mast cells, macrophages, and hematopoietic stem/progenitor cells. Further, epithelial cells and neurons have been recognized as important regulators of type 2 immunity. Collectively, these pathways stimulate host-protective responses necessary for worm expulsion and the healing of affected tissues. In this review we focus on the innate immune pathways that regulate immunity to helminth parasites and describe how better understanding of these pathways may lead to the development of new therapeutic strategies.}, } @article {pmid30177446, year = {2018}, author = {Langgut, D and Almogi-Labin, A and Bar-Matthews, M and Pickarski, N and Weinstein-Evron, M}, title = {Evidence for a humid interval at ∼56-44 ka in the Levant and its potential link to modern humans dispersal out of Africa.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {75-90}, doi = {10.1016/j.jhevol.2018.08.002}, pmid = {30177446}, issn = {1095-8606}, abstract = {This study provides a detailed reconstruction of the paleoenvironmental conditions that prevailed during one of the periods of modern human migration out of Africa and their occupation of the Eastern Mediterranean-Levant during the Late Middle Paleolithic-Early Upper Paleolithic. Tracing the past vegetation and climate within the Eastern Mediterranean-Levant region is largely based on a south-eastern Mediterranean marine pollen record covering the last 90 kyr (core MD-9509). The various palynomorphs were linked to distinct vegetation zones that were correlated to the two climate systems affecting the study area: the low-latitude monsoon system and the North Atlantic-Mediterranean climate system. The bioprovince palynological markers show that during the period between ∼56 and 44 ka, which covers the early part of Marine Isotope Stage 3 (MIS 3), there was an increase in transportation of pollen from Nilotic origin and a rise in dinoflagellate cyst ratios. These changes coincided with maximum insolation values at 65°N, which led to an enhancement in Nile River discharge into the Eastern Mediterranean following the intensification of the African monsoonal system. At the same time, the rise in Mediterranean arboreal pollen values (broadleaved, coniferous and deciduous temperate trees) is most likely driven by increased precipitation related to the intensification of the North Atlantic-Mediterranean climate system. The ∼56-44 ka wet event coincides with Dansgaard-Oeschger interstadials 14 and 12 and with a warming phase in the Levant, as evidenced by the melting of permafrost along the higher elevations of Mount Hermon. We suggest that African modern humans were able to cross the harsher arid areas due to the intensification of the monsoonal system during the first part of MIS 3, and inhabit the Eastern Mediterranean-Levant region where climatic conditions were favorable (wetter and warmer), even in the currently semiarid/steppe regions.}, } @article {pmid30177445, year = {2018}, author = {Goldfield, AE and Booton, R and Marston, JM}, title = {Modeling the role of fire and cooking in the competitive exclusion of Neanderthals.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {91-104}, doi = {10.1016/j.jhevol.2018.07.006}, pmid = {30177445}, issn = {1095-8606}, abstract = {The Neanderthal body was more robust and energetically costly than the bodies of anatomically modern humans (AMH). Different metabolic budgets between competing populations of Neanderthals and AMH may have been a factor in the varied ranges of behavior and timelines for Neanderthal extinction that we see in the Paleolithic archaeological record. This paper uses an adaptation of the Lotka-Volterra model to determine whether metabolic differences alone could have accounted for Neanderthal extinction. In addition, we use a modeling approach to investigate Neanderthal fire use, evidence for which is much debated and is variable throughout different climatic phases of the Middle Paleolithic. The increased caloric yield from a cooked versus a raw diet may have played an important role in population competition between Neanderthals and AMH. We arrive at two key conclusions. First, given differences in metabolic budget between Neanderthals and AMH and their dependence on similar or overlapping food resources, Neanderthal extinction is likely inevitable over the long term. Second, the rate of Neanderthal extinction increases as the frequency of AMH fire use increases. Results highlight the importance of understanding the variable behaviors at play on a regional scale in order to understand global Neanderthal extinction. We also emphasize the importance of understanding the role of fire use in the Middle to Upper Paleolithic transition.}, } @article {pmid30177439, year = {2018}, author = {van Wezel, GP and Wright, GD}, title = {Editorial overview: Antimicrobials.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {iii-v}, doi = {10.1016/j.mib.2018.08.001}, pmid = {30177439}, issn = {1879-0364}, } @article {pmid30177410, year = {2018}, author = {Nguyen, TC and Zaleta-Rivera, K and Huang, X and Dai, X and Zhong, S}, title = {RNA, Action through Interactions.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {11}, pages = {867-882}, pmid = {30177410}, issn = {0168-9525}, support = {DP1 HD087990/HD/NICHD NIH HHS/United States ; R01 HG008135/HG/NHGRI NIH HHS/United States ; }, abstract = {As transcription of the human genome is quite pervasive, it is possible that many novel functions of the noncoding genome have yet to be identified. Often the noncoding genome's functions are carried out by their RNA transcripts, which may rely on their structures and/or extensive interactions with other molecules. Recent technology developments are transforming the fields of RNA biology from studying one RNA at a time to transcriptome-wide mapping of structures and interactions. Here, we highlight the recent advances in transcriptome-wide RNA interaction analysis. These technologies revealed surprising versatility of RNA to participate in diverse molecular systems. For example, tens of thousands of RNA-RNA interactions have been revealed in cultured cells as well as in mouse brain, including interactions between transposon-produced transcripts and mRNAs. In addition, most transcription start sites in the human genome are associated with noncoding RNA transcribed from other genomic loci. These recent discoveries expanded our understanding of RNAs' roles in chromatin organization, gene regulation, and intracellular signaling.}, } @article {pmid30177306, year = {2018}, author = {Noë, R and Kiers, ET}, title = {Mycorrhizal Markets, Firms, and Co-ops.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {777-789}, doi = {10.1016/j.tree.2018.07.007}, pmid = {30177306}, issn = {1872-8383}, abstract = {The nutrient exchange mutualism between arbuscular mycorrhizal fungi (AMFs) and their host plants qualifies as a biological market, but several complications have hindered its appropriate use. First, fungal 'trading agents' are hard to identify because AMFs are potentially heterokaryotic, that is, they may contain large numbers of polymorphic nuclei. This means it is difficult to define and study a fungal 'individual' acting as an independent agent with a specific trading strategy. Second, because nutrient exchanges occur via communal structures (arbuscules), this temporarily reduces outbidding competition and transaction costs and hence resembles exchanges among divisions of firms, rather than traditional trade on markets. We discuss how fungal nuclei may coordinate their trading strategies, but nevertheless retain some independence, similar to human co-operatives (co-ops).}, } @article {pmid30176937, year = {2018}, author = {von Schalburg, KR and Rondeau, EB and Leong, JS and Davidson, WS and Koop, BF}, title = {Regulatory processes that control haploid expression of salmon sperm mRNAs.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {639}, pmid = {30176937}, issn = {1756-0500}, mesh = {3' Untranslated Regions ; 5' Untranslated Regions ; Animals ; *Haploidy ; Male ; *RNA, Messenger ; Salmon/*metabolism ; Spermatozoa ; }, abstract = {OBJECTIVE: Various stages of mRNA processing are necessary for functionally important genes required during late-stage sperm differentiation. Protein-RNA complexes form that edit, stabilize, store, deliver, localize and regulate translation of sperm mRNAs. These regulatory processes are often directed by recognition sequence elements and the particular composition of the proteins associated with the mRNAs. Previous work has shown that the cAMP response element modulator (CREM), estrogen receptor-alpha (ERα) and forkhead box L2A (FOXL2A) proteins are present in late-stage salmon sperm. Here we investigate whether these and other regulatory proteins might control processing of mRNAs not expressed until the haploid stage of development. We also examine regulatory processes that prepare and present mRNAs that generate unique products essential for differentiating sperm (i.e. for flagellar assembly and function).

RESULTS: We provide evidence for potential sperm-specific recognition elements in 5'-untranslated regions (utrs) that may bind CREM, ERα, FOXL2A, Y-box and other proteins. We show that changes within the 5'-utrs and open reading frames of some sperm genes lead to distinct protein termini that may provide specific interfaces necessary for localization and function within the paternal gamete.}, } @article {pmid30176927, year = {2018}, author = {Sintusek, P and Sa-Nguanmoo, P and Posuwan, N and Jaroonvanichkul, V and Vorayingyong, A and Poovorawan, Y}, title = {Changes in hepatitis A virus (HAV) seroprevalence in medical students in Bangkok, Thailand, from 1981 to 2016.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {640}, pmid = {30176927}, issn = {1756-0500}, support = {P-15-50004//National Science and Technology Development Agency (NSTDA) Research Chair Grant/ ; GLE 58-014-30-004//Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Hospital/ ; RES560530093//Center of Excellence in Clinical Virology at Chulalongkorn University and Chulalongkorn Hospital/ ; }, mesh = {Adolescent ; Female ; Hepatitis A/*epidemiology ; Hepatitis A Antibodies ; Hepatitis A virus/*isolation & purification ; Humans ; Male ; Seroepidemiologic Studies ; *Students, Medical ; Thailand/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: This study aimed to determine the seroprevalence of anti-HAV IgG in Thai medical students in 2016 compared with the previous data and to demonstrate the cross-effective strategy to screen HAV seropositivity.

RESULTS: Sera from 176 first-year medical students (age 19.07 ± 0.59 years; 50% female) at a university hospital in Thailand were tested for anti-HAV IgG. Data from HAV vaccination records and questionnaires were also collected. HAV seropositivity was unexpectedly high (62.5%, n = 110). 37.5% (n = 66) had an HAV vaccination record. Of these, 60.6% received the full HAV vaccination series, 4.5% received one HAV vaccination, 34.8% did not receive HAV vaccination, and 3.0% had natural HAV immunity. The long-term efficacy of HAV vaccination was at least 97.5% over a mean of 15.55 ± 2.44 years. There was a significant difference in immunity between students with (66.7%) and without (50.9%) vaccination records (P = 0.028). Most of the student's parents had a bachelor's degree or higher (87.9%; n = 272) and above average income (mean 17,000.76 ± 194.22 USD/person/year). Parental education and socioeconomic status influenced vaccination accessibility in these medical students. Screening of vaccination records instead of routine anti-HAV IgG testing is a cost-effective and reliable strategy to determine HAV immunity in medical students in Thailand.}, } @article {pmid30176922, year = {2018}, author = {Bedaso, A and Kediro, G and Yeneabat, T}, title = {Factors associated with depression among prisoners in southern Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {637}, pmid = {30176922}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; *Depression ; Ethiopia/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Prevalence ; Prisoners/*psychology ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: To assess the prevalence of depression and associated factors among prisoners in Hawassa Central Correctional Institution, Hawassa, SNNPR, Ethiopia.

RESULT: 56.4% of study participants had significant depressive symptoms. During Multiple logistic regression, depression was significantly associated with not participating in income generating activities inside the prison [AOR = 0.531 95% CI (0.32, 0.87)], History of Chronic disease [AOR = 2.62 95% CI (1.29, 5.32)] and history of Khat chewing [AOR = 2.47, 95% CI (1.04-5.85)].}, } @article {pmid30176920, year = {2018}, author = {Johannsen, S and Schick, M and Roewer, N and Schuster, F}, title = {Microdialysis and ultrasound elastography for monitoring of localized muscular reaction after pharmacological stimulation in rats.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {636}, pmid = {30176920}, issn = {1756-0500}, mesh = {Animals ; Caffeine ; *Elasticity Imaging Techniques ; Halothane ; Malignant Hyperthermia ; *Microdialysis ; Muscle Contraction ; Muscle, Skeletal/*diagnostic imaging/physiology ; Rats ; }, abstract = {OBJECTIVE: Halothane and caffeine are known to cause skeletal muscular contractions in vitro and have been proven to induce circumscribed metabolic reactions when injected into rat skeletal muscle. In this study 26 rats were investigated by either continuous application of calcium 160 mM or bolus injection of caffeine 160 mM or halothane 10% vol via a microdialysis probe in the tibialis anterior muscle. Tissue elasticity at the injection site was monitored by ultrasound strain elastography. Aim of this study was to detect (I) changes in local lactate concentrations and (II) whether these can be attributed to a muscular contraction detected by ultrasound elastography.

RESULTS: Localized metabolic reactions were verified by increasing intramuscular lactate concentrations following continuous application of calcium (0.6 [0.3;0.6] to 3.6 [3.0;4.3] mmol/l after 60 min) and bolus application of caffeine (0.2 [0.2;0.3] to 1.6 [0.9;1.9] mmol/l after 30 min) and halothane (0.3 [0.1;0.3] to 4.7 [4.3;6.3] mmol/l after 30 min). However, ultrasound elastography did not detect any differences in tissue elasticity compared to control animals. The authors identified potential limitations of the study conditions, which might be crucial to avoid for future investigations.}, } @article {pmid30176917, year = {2018}, author = {Diaba-Nuhoho, P and Ofori, EK and Asare-Anane, H and Oppong, SY and Boamah, I and Blackhurst, D}, title = {Impact of exercise intensity on oxidative stress and selected metabolic markers in young adults in Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {634}, pmid = {30176917}, issn = {1756-0500}, support = {UGPSS//University of Ghana Postgraduate Scholarship Scheme (UGPSS) for part-funding this study/ ; }, mesh = {Adult ; Antioxidants ; Biomarkers ; Exercise/*physiology ; Female ; Ghana ; Humans ; Lactation ; Malondialdehyde ; *Oxidative Stress ; Superoxide Dismutase/metabolism ; Young Adult ; }, abstract = {OBJECTIVE: This study aimed to evaluate the effect of different levels of exercise on markers of oxidative stress and selected metabolic parameters in Ghanaian young adults.

RESULTS: Significant increases in a marker of oxidative stress malondialdehyde and antioxidants such as superoxide dismutase and uric acid were observed in the exercisers compared with the inactive group (p < 0.05). Total cholesterol and high density lipoprotein levels were significantly different (p < 0.05) between the two groups. Positive associations between exercise intensity, antioxidant concentration and malondialdehyde were observed within the exercise group for vigorous exercise with regards to uric acid, superoxide dismutase and malondialdehyde (r = 0.512, p = 0.004; r = 0.810, p = 0.001; r = 0.715, p = 0.001) respectively and moderate exercise vs malondialdehyde (r = 0.841, p = 0.001) compared to the inactive group. Exercise participants performed more vigorous exercise (p < 0.001), moderate exercise (p < 0.001) and more walking (p < 0.001) compared with the inactive group while the inactive group exhibited more sitting (p < 0.001). The study provides a first report on the risk associated with increase in oxidative stress and the importance of walking as a health promotion intervention among young Ghanaian adults.}, } @article {pmid30176912, year = {2018}, author = {Flueck, WT}, title = {Elusive cranial lesions severely afflicting young endangered Patagonian huemul deer.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {638}, pmid = {30176912}, issn = {1756-0500}, mesh = {Animals ; *Animals, Wild ; Brain Diseases/*veterinary ; *Deer ; Endangered Species ; Male ; }, abstract = {OBJECTIVES: Most subpopulations of endangered huemul deer (Hippocamelus bisulcus) fail to recover, frequently due to osteopathology. Equivalent pathology was detected only postmortem in an additional deer 365 km further north, stressing the need to improve clinical evaluations of live huemul.

RESULTS: Captured on a farm and attended by authorities in charge of huemul, the deer was considered apt for relocation and release. Delays with attendance and lack of reversal drugs resulted in his death. The subsequent necropsy revealed severe osteopathology particularly in mandibles and maxillae. Such disease in another southern population affected 57+ % among dead adults, and 86% among live adults. The present case stems from a new subpopulation, isolated 365 km further north. Such severe pathology demands that individuals be rehabilitated, especially relevant with severely endangered species, because liberations will cause premature death and loss of reproductive lifetime. Live huemul must be examined utmost professionally especially regarding this pathophysiognomy. This incidence represents the typical situation of extant huemul, being displaced from their traditional migratory behavior to utilize fertile low-elevation habitat. This young male may have been dispersing, but reaching valleys usually leads to death due to locally intense anthropogenic activities.}, } @article {pmid30176910, year = {2018}, author = {Abraha, TH and Teferra, AS and Gelagay, AA and Welesamuel, TG and Fisseha, GK and Aregawi, BG and Belay, DS}, title = {Knowledge and associated factors of lactational amenorrhea as a contraception method among postpartum women in Aksum town, Tigray Region, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {641}, pmid = {30176910}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; *Amenorrhea ; *Contraception ; Cross-Sectional Studies ; Ethiopia ; Family Planning Services ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; *Lactation ; *Postpartum Period ; Pregnancy ; Young Adult ; }, abstract = {OBJECTIVES: The objective of the study was to assess the prevalence of knowledge level and predictors of lactational amenorrhea method (LAM) as method of contraception among women who gave birth a year prior to the study period in the Aksum town, Tigray Region. The study was cross sectional in design conducted from March 25 to April 24, 2015. Results of the study could help the design of family planning strategies.

RESULTS: The knowledge status of LAM as a contraceptive method was 8.8% [95% CI 6.4-11%)]. Women who delivered at health institution (AOR = 1.4, 95% CI 1.2-4.3), attended postnatal care (AOR = 1.3, 95% CI 1.2-3.0) and visited home and counseled about family planning by health extension in the last 12 months, (AOR = 1.5, 95% CI 1.3-4.0) were more likely found knowledgeable towards LAM. Secondary and above level of the maternal education was also found a significant predictor variable with LAM as a contraceptive method (AOR = 1.2 95% CI 1.1-4.0). Our findings recommend that to address the knowledge gap of mothers; improving the uptake of maternal health services and strengthening family planning counseling at home are a key area for improving the knowledge level of LAM.}, } @article {pmid30176909, year = {2018}, author = {Romano E Silva, AC and Dias, GM and de Carvalho, JJ and De Lorenzo, A and Kasal, DAB}, title = {Research proposal: inflammation and oxidative stress in coronary artery bypass surgery graft: comparison between diabetic and non-diabetic patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {635}, pmid = {30176909}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; *Coronary Artery Bypass ; Coronary Artery Disease/*immunology/physiopathology ; Cross-Sectional Studies ; Diabetes Complications ; Diabetes Mellitus ; Humans ; *Inflammation ; Male ; *Oxidative Stress ; Research Design ; }, abstract = {BACKGROUND: Diabetes mellitus patients (DM) have more severe progression of atherosclerotic disease than non-diabetic (NDM) individuals. In situ inflammation and oxidative stress are key points in the pathophysiology of atherosclerosis, a concept largely based on animal model research. There are few studies comparing inflammation and oxidative stress parameters in medium-sized arteries between DM and NDM patients. A fragment of the internal mammary artery used in coronary artery bypass grafting (CABG) will be employed for this purpose OBJECTIVE: To assess the expression of inflammatory markers tumor necrosis factor-α, transforming growth factor-β1, nuclear factor kappa B, the enzymes superoxide dismutase, and catalase in the vascular wall of the arterial graft used in CABG, comparing DM and NDM patients RESULTS: The present study will add information to the vascular degenerative processes occurring in diabetic patients.}, } @article {pmid30176901, year = {2018}, author = {Yuda, M}, title = {Public and social environment changes and caesarean section delivery choice in Japan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {633}, pmid = {30176901}, issn = {1756-0500}, support = {26780180//Japan Society for the Promotion of Science/ ; }, mesh = {Adult ; *Cesarean Section ; Female ; Humans ; Japan ; Parturition ; Pregnancy ; *Social Environment ; }, abstract = {OBJECTIVE: As in many other countries, the ratio of caesarean section (c-section) delivery to total births in Japan is rising steadily, while the total number of deliveries is decreasing. Although c-sections can effectively prevent maternal and perinatal mortality and morbidity when medically justified, it is uncertain how medically unnecessary c-sections affect the short-, middle-, and long-term postnatal effects on the mother and child. As there are no empirical studies on c-section choice for Japan, this study uses individual medical facility panel data from 1999 to 2014 to comprehensively examine the effects of recent public and social environment changes on c-section delivery choice.

RESULTS: The empirical results from our fixed effect model show that c-section delivery and its ratio are higher in public hospitals, in relatively large clinics, and in clinics opening on holidays. In addition, increases in the lump-sum birth allowance and the number of medical malpractice lawsuits also increase the number of c-section delivery.}, } @article {pmid30176859, year = {2018}, author = {Zhai, X and Zhang, Y and Wang, K and Chen, Q and Li, S and Huang, D}, title = {Grazing effects on the nutritive value of dominant species in steppe grasslands of northern China.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {30}, pmid = {30176859}, issn = {1472-6785}, abstract = {BACKGROUND: Forage nutritive value plays an important role in livestock nutrition and maintaining sustainable grassland ecosystems, and grazing management can affect the quality of forage. In this study, we investigated the effects of different grazing intensities on the nutritive values of Leymus chinensis (Trin.) Tzvelev, Artemisia spp. and Carex duriuscula C. A. Mey in the steppes of China during the growing seasons from 2011 to 2013. Five grazing management treatments were implemented: (1) rest grazing in spring, heavy grazing in summer and moderate grazing in autumn (RHM), (2) rest grazing in spring, moderate grazing in summer and heavy grazing in autumn (RMH), (3) heavy grazing though all seasons (HHH), (4) heavy grazing in spring and summer and moderate grazing in autumn (HHM) and (5) continuous moderate grazing in all seasons (MMM).

RESULTS: There were significant effects of year, season, treatment, and year × season and year × treatment interactions only on the crude protein of L. chinensis (P < 0.05). The crude protein concentrations of L. chinensis in the plots of constant high grazing pressure (HHH) and reduced grazing pressure in the last grazing stage (HHM) were higher than with deferred grazing (RMH and RHM, P < 0.05) in spring from 2011 to 2012. For Artemisia spp. and C. duriuscula, the crude protein concentration in HHH was higher than that in RMH (P < 0.05) in the summer of 2011. There were no significant differences (P > 0.05) for ether extract, neutral detergent fiber, acid detergent fiber and Ca concentration for any of the grasses in spring and summer from 2011 to 2013 under the different grazing management treatments.

CONCLUSIONS: The nutritive value of L. chinensis was more responsive to grazing disturbance than Artemisia spp. and C. duriuscula, and heavy grazing maintained a relatively high crude protein content in all species. Seasonal and interannual seasonal differences in grazing management combinations were two of the most important factors in determining the variability of forage nutritive value, including crude protein, ether extract, neutral detergent fiber, acid detergent fiber and calcium, for L. chinensis, Artemisia spp. and C. duriuscula. We suggest that moderate grazing should be adopted to ensure the quality and yield of forage and promote the sustainable development of animal husbandry.}, } @article {pmid30176818, year = {2018}, author = {Sanders, SM and Ma, Z and Hughes, JM and Riscoe, BM and Gibson, GA and Watson, AM and Flici, H and Frank, U and Schnitzler, CE and Baxevanis, AD and Nicotra, ML}, title = {CRISPR/Cas9-mediated gene knockin in the hydroid Hydractinia symbiolongicarpus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {649}, pmid = {30176818}, issn = {1471-2164}, support = {ZIA-HG000140//National Human Genome Research Institute/ ; T32 AI074490/AI/NIAID NIH HHS/United States ; ZIA HG000140/HG/NHGRI NIH HHS/United States ; 11/PI/1020//Science Foundation Ireland/Ireland ; IOS1557339//Division of Integrative Organismal Systems/ ; T32AI074490//National Institutes of Health/ ; }, mesh = {Animals ; *CRISPR-Cas Systems ; *Gene Editing ; *Gene Knock-In Techniques ; Genetic Vectors ; Homologous Recombination ; Hydrozoa/*genetics/growth & development ; Peptide Elongation Factor 1/*genetics ; Transgenes ; }, abstract = {BACKGROUND: Hydractinia symbiolongicarpus, a colonial cnidarian, is a tractable model system for many cnidarian-specific and general biological questions. Until recently, tests of gene function in Hydractinia have relied on laborious forward genetic approaches, randomly integrated transgenes, or transient knockdown of mRNAs.

RESULTS: Here, we report the use of CRISPR/Cas9 genome editing to generate targeted genomic insertions in H. symbiolonigcarpus. We used CRISPR/Cas9 to promote homologous recombination of two fluorescent reporters, eGFP and tdTomato, into the Eukaryotic elongation factor 1 alpha (Eef1a) locus. We demonstrate that the transgenes are expressed ubiquitously and are stable over two generations of breeding. We further demonstrate that CRISPR/Cas9 genome editing can be used to mark endogenous proteins with FLAG or StrepII-FLAG affinity tags to enable in vivo and ex vivo protein studies.

CONCLUSIONS: This is the first account of CRISPR/Cas9 mediated knockins in Hydractinia and the first example of the germline transmission of a CRISPR/Cas9 inserted transgene in a cnidarian. The ability to precisely insert exogenous DNA into the Hydractinia genome will enable sophisticated genetic studies and further development of functional genomics tools in this understudied cnidarian model.}, } @article {pmid30176810, year = {2018}, author = {Lienemann, T and Beyer, W and Pelkola, K and Rossow, H and Rehn, A and Antwerpen, M and Grass, G}, title = {Genotyping and phylogenetic placement of Bacillus anthracis isolates from Finland, a country with rare anthrax cases.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {102}, pmid = {30176810}, issn = {1471-2180}, abstract = {BACKGROUND: Anthrax, the zoonotic disease caused by the gram-positive bacterium Bacillus anthracis, is nowadays rare in northern parts of Europe including Finland and Scandinavia. Only two minor outbreaks of anthrax in 1988 and in 2004 and one sporadic infection in 2008 have been detected in animals in Finland since the 1970's. Here, we report on two Finnish B. anthracis strains that were isolated from spleen and liver of a diseased calf related to the outbreak in 1988 (strain HKI4363/88) and from a local scrotum and testicle infection of a bull in 2008 (strain BA2968). These infections occurred in two rural Finnish regions, i.e., Ostrobothnia in western Finland and Päijänne Tavastia in southern Finland, respectively.

RESULTS: The isolates were genetically characterized by PCR-based methods such as multilocus variable number of tandem repeat analysis (MLVA) and whole genome-sequence analysis (WGS). Phylogenetic comparison of the two strains HKI4363/88 and BA2968 by chromosomal single nucleotide polymorphism (SNP) analysis grouped these organisms within their relatives of the minor canonical A-branch canSNP-group A.Br.003/004 (A.Br.V770) or canonical B-branch B.Br.001/002, respectively. Strain HKI4363/88 clustered relatively closely with other members of the A.Br.003/004 lineage from Europe, South Africa, and South America. In contrast, strain BA2968 clearly constituted a new sublineage within B.Br.001/002 with its closest relative being HYO01 from South Korea.

CONCLUSIONS: Our results suggest that Finland harbors both unique (autochthonous) and more widely distributed, common clades of B. anthracis. We suspect that members of the common clades such as strains HKI4363/88 have been introduced only recently by anthropogenic activities involving importation of contaminated animal products. On the other hand, autochthonous strains such as isolate BA2968 probably have an older history of their introduction into Finland as evidenced by a high number of single nucleotide variant sites in their genomes.}, } @article {pmid30176808, year = {2018}, author = {Girgis, HZ and Velasco, A and Reyes, ZE}, title = {HebbPlot: an intelligent tool for learning and visualizing chromatin mark signatures.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {310}, pmid = {30176808}, issn = {1471-2105}, mesh = {Chromatin/*chemistry/*genetics ; *Epigenomics ; *Gene Expression Regulation ; Histones/*metabolism ; Humans ; *Promoter Regions, Genetic ; Protein Processing, Post-Translational ; Regulatory Sequences, Nucleic Acid ; *Software ; }, abstract = {BACKGROUND: Histone modifications play important roles in gene regulation, heredity, imprinting, and many human diseases. The histone code is complex and consists of more than 100 marks. Therefore, biologists need computational tools to characterize general signatures representing the distributions of tens of chromatin marks around thousands of regions.

RESULTS: To this end, we developed a software tool, HebbPlot, which utilizes a Hebbian neural network in learning a general chromatin signature from regions with a common function. Hebbian networks can learn the associations between tens of marks and thousands of regions. HebbPlot presents a signature as a digital image, which can be easily interpreted. Moreover, signatures produced by HebbPlot can be compared quantitatively. We validated HebbPlot in six case studies. The results of these case studies are novel or validating results already reported in the literature, indicating the accuracy of HebbPlot. Our results indicate that promoters have a directional chromatin signature; several marks tend to stretch downstream or upstream. H3K4me3 and H3K79me2 have clear directional distributions around active promoters. In addition, the signatures of high- and low-CpG promoters are different; H3K4me3, H3K9ac, and H3K27ac are the most different marks. When we studied the signatures of enhancers active in eight tissues, we observed that these signatures are similar, but not identical. Further, we identified some histone modifications - H3K36me3, H3K79me1, H3K79me2, and H4K8ac - that are associated with coding regions of active genes. Other marks - H4K12ac, H3K14ac, H3K27me3, and H2AK5ac - were found to be weakly associated with coding regions of inactive genes.

CONCLUSIONS: This study resulted in a novel software tool, HebbPlot, for learning and visualizing the chromatin signature of a genetic element. Using HebbPlot, we produced a visual catalog of the signatures of multiple genetic elements in 57 cell types available through the Roadmap Epigenomics Project. Furthermore, we made a progress toward a functional catalog consisting of 22 histone marks. In sum, HebbPlot is applicable to a wide array of studies, facilitating the deciphering of the histone code.}, } @article {pmid30176805, year = {2018}, author = {Matthee, CA and Engelbrecht, A and Matthee, S}, title = {Comparative phylogeography of parasitic Laelaps mites contribute new insights into the specialist-generalist variation hypothesis (SGVH).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {131}, pmid = {30176805}, issn = {1471-2148}, support = {Incentive Funding//National Research Foundation/International ; }, mesh = {Animals ; Base Sequence ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Genetic Variation ; Geography ; Haplotypes/genetics ; Host Specificity ; Mites/*classification/genetics ; Mitochondria/genetics ; *Models, Biological ; Murinae/genetics/parasitology ; Parasites/*classification/genetics ; *Phylogeography ; }, abstract = {BACKGROUND: The specialist-generalist variation hypothesis (SGVH) in parasites suggests that, due to patchiness in habitat (host availability), specialist species will show more subdivided population structure when compared to generalist species. In addition, since specialist species are more prone to local stochastic extinction events with their hosts, they will show lower levels of intraspecific genetic diversity when compared to more generalist.

RESULTS: To test the wider applicability of the SGVH we compared 337 cytochrome oxidase I mitochondrial DNA and 268 nuclear tropomyosin DNA sequenced fragments derived from two co-distributed Laelaps mite species and compared the data to 294 COI mtDNA sequences derived from the respective hosts Rhabdomys dilectus, R. bechuanae, Mastomys coucha and M. natalensis. In support of the SGVH, the generalist L. muricola was characterized by a high mtDNA haplotypic diversity of 0.97 (±0.00) and a low level of population differentiation (mtDNA Fst = 0.56, p < 0.05; nuDNA Fst = 0.33, P < 0.05) while the specialist L. giganteus was overall characterized by a lower haplotypic diversity of 0.77 (±0.03) and comparatively higher levels of population differentiation (mtDNA Fst = 0.87, P < 0.05; nuDNA Fst = 0.48, P < 0.05). When the two specialist L. giganteus lineages, which occur on two different Rhabdomys species, are respectively compared to the generalist parasite, L. muricola, the SGVH is not fully supported. One of the specialist L. giganteus species occurring on R. dilectus shows similar low levels of population differentiation (mtDNA Fst = 0.53, P < 0.05; nuDNA Fst = 0.12, P < 0.05) than that found for the generalist L. muricola. This finding can be correlated to differences in host dispersal: R. bechuanae populations are characterized by a differentiated mtDNA Fst of 0.79 (P < 0.05) while R. dilectus populations are less structured with a mtDNA Fst = 0.18 (P < 0.05).

CONCLUSIONS: These findings suggest that in ectoparasites, host specificity and the vagility of the host are both important drivers for parasite dispersal. It is proposed that the SGHV hypothesis should also incorporate reference to host dispersal since in our case only the specialist species who occur on less mobile hosts showed more subdivided population structure when compared to generalist species.}, } @article {pmid30176804, year = {2018}, author = {Xu, H and Tang, F and Dai, J and Wang, C and Zhou, X}, title = {Ultrasensitive and rapid count of Escherichia coli using magnetic nanoparticle probe under dark-field microscope.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {100}, pmid = {30176804}, issn = {1471-2180}, abstract = {BACKGROUND: Escherichia coli (E. coli) is one of the best-known zoonotic bacterial species, which pathogenic strain can cause infections in humans and animals. However, existing technologies or methods are deficient for quickly on-site identifying infection of E. coli before they breakout. Herein, we present an ultrasensitive and on-site method for counting E. coli using magnetic nanoparticle (MNP) probe under a dark-field in 30 min.

RESULTS: The antibodies functionalized MNP, binding to E. coli to form a golden ring-like structure under a dark-field microscope, allowing for counting E. coli. This method via counting MNP-conjugated E. coli under dark-field microscope demonstrated the sensitivity of 6 CFU/μL for E. coli detection. Importantly, due to the advantages such as time-saving (only 30 min) and almost free of instrument (only require a portable microscope), our MNP-labeled dark-field counting strategy has the potential of being a universal tool for on-site quantifying a variety of pathogens with size ranges from a few hundreds of nanometers to a few micrometers.

CONCLUSION: In summary, the MNP-labeled dark-field counting strategy is a rapid, simple, sensitive as well as low-cost assay strategy, which has the potential of being a universal tool for on-site quantification of micrometer-size pathogens like E. coli.}, } @article {pmid30176803, year = {2018}, author = {Tsuchiya, K and Cao, YY and Kurokawa, M and Ashino, K and Yomo, T and Ying, BW}, title = {A decay effect of the growth rate associated with genome reduction in Escherichia coli.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {101}, pmid = {30176803}, issn = {1471-2180}, abstract = {BACKGROUND: Bacterial growth is an important topic in microbiology and of crucial importance to better understand living cells. Bacterial growth dynamics are quantitatively examined using various methods to determine the physical, chemical or biological features of growing populations. Due to methodological differences, the exponential growth rate, which is a parameter that is representative of growth dynamics, should be differentiated. Ignoring such differentiation in the growth analysis might overlook somehow slight but significant changes in cellular features of the growing population. Both experimental and theoretical investigations are required to address these issues.

RESULTS: This study experimentally verified the differentiation in growth rates attributed to different methodologies, and demonstrated that the most popular method, optical turbidity, led to the determination of a lower growth rate in comparison to the methods based on colony formation and cellular adenosine triphosphate, due to a decay effect of reading OD600 during a population increase. Accordingly, the logistic model, which is commonly applied to the high-throughput growth data reading the OD600, was revised by introducing a new parameter: the decay rate, to compensate for the lowered estimation in growth rates. An improved goodness of fit in comparison to the original model was acquired due to this revision. Applying the modified logistic model to hundreds of growth data acquired from an assortment of Escherichia coli strains carrying the reduced genomes led to an intriguing finding of a correlation between the decay rate and the genome size. The decay effect seemed to be partially attributed to the decrease in cell size accompanied by a population increase and was medium dependent.

CONCLUSIONS: The present study provides not only an improved theoretical tool for the high-throughput studies on bacterial growth dynamics linking with optical turbidity to biological meaning, but also a novel insight of the genome reduction correlated decay effect, which potentially reflects the changing cellular features during population increase. It is valuable for understanding the genome evolution and the fitness increase in microbial life.}, } @article {pmid30176802, year = {2018}, author = {Honkola, T and Ruokolainen, K and Syrjänen, KJJ and Leino, UP and Tammi, I and Wahlberg, N and Vesakoski, O}, title = {Evolution within a language: environmental differences contribute to divergence of dialect groups.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {132}, pmid = {30176802}, issn = {1471-2148}, support = {46-13114//Koneen Säätiö (FI)/International ; 46-13114//Koneen Säätiö/International ; 46-13114//Koneen Säätiö/International ; }, mesh = {Adaptation, Physiological ; *Biological Evolution ; Culture ; *Environment ; Finland ; Genetic Variation ; Geography ; Humans ; *Language ; Linguistics ; Models, Theoretical ; }, abstract = {BACKGROUND: The processes leading to the diversity of over 7000 present-day languages have been the subject of scholarly interest for centuries. Several factors have been suggested to contribute to the spatial segregation of speaker populations and the subsequent linguistic divergence. However, their formal testing and the quantification of their relative roles is still missing. We focussed here on the early stages of the linguistic divergence process, that is, the divergence of dialects, with a special focus on the ecological settings of the speaker populations. We adopted conceptual and statistical approaches from biological microevolution and parallelled intra-lingual variation with genetic variation within a species. We modelled the roles of geographical distance, differences in environmental and cultural conditions and in administrative history on linguistic divergence at two different levels: between municipal dialects (cf. in biology, between individuals) and between dialect groups (cf. in biology, between populations).

RESULTS: We found that geographical distance and administrative history were important in separating municipal dialects. However, environmental and cultural differences contributed markedly to the divergence of dialect groups. In biology, increase in genetic differences between populations together with environmental differences may suggest genetic differentiation of populations through adaptation to the local environment. However, our interpretation of this result is not that language itself adapts to the environment. Instead, it is based on Homo sapiens being affected by its environment, and its capability to adapt culturally to various environmental conditions. The differences in cultural adaptations arising from environmental heterogeneity could have acted as nonphysical barriers and limited the contacts and communication between groups. As a result, linguistic differentiation may emerge over time in those speaker populations which are, at least partially, separated.

CONCLUSIONS: Given that the dialects of isolated speaker populations may eventually evolve into different languages, our result suggests that cultural adaptation to local environment and the associated isolation of speaker populations have contributed to the emergence of the global patterns of linguistic diversity.}, } @article {pmid30176801, year = {2018}, author = {Zhang, D and Zou, H and Wu, SG and Li, M and Jakovlić, I and Zhang, J and Chen, R and Li, WX and Wang, GT}, title = {Three new Diplozoidae mitogenomes expose unusual compositional biases within the Monogenea class: implications for phylogenetic studies.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {133}, pmid = {30176801}, issn = {1471-2148}, support = {CARS-46-08//Earmarked Fund for China Agriculture Research System/International ; 31572658//National Natural Science Foundation of China/International ; 2015ABA045//Major Scientific and Technological Innovation Project of Hubei Province/International ; }, mesh = {Amino Acids/genetics ; Animals ; Base Composition/*genetics ; Base Sequence ; Bias ; Codon/genetics ; Gene Order ; Genetic Variation ; *Genome, Mitochondrial ; Genomics ; Molecular Sequence Annotation ; Nucleic Acid Conformation ; Nucleotides/genetics ; Open Reading Frames/genetics ; *Phylogeny ; RNA, Transfer/genetics ; Selection, Genetic ; Trematoda/*genetics ; }, abstract = {BACKGROUND: As the topologies produced by previous molecular and morphological studies were contradictory and unstable (polytomy), evolutionary relationships within the Diplozoidae family and the Monogenea class (controversial relationships among the Discocotylinea, Microcotylinea and Gastrocotylinea suborders) remain unresolved. Complete mitogenomes carry a relatively large amount of information, sufficient to provide a much higher phylogenetic resolution than traditionally used morphological traits and/or single molecular markers. However, their implementation is hampered by the scarcity of available monogenean mitogenomes. Therefore, we sequenced and characterized mitogenomes belonging to three Diplozoidae family species, and conducted comparative genomic and phylogenomic analyses for the entire Monogenea class.

RESULTS: Taxonomic identification was inconclusive, so two of the species were identified merely to the genus level. The complete mitogenomes of Sindiplozoon sp. and Eudiplozoon sp. are 14,334 bp and 15,239 bp in size, respectively. Paradiplozoon opsariichthydis (15,385 bp) is incomplete: an approximately 2000 bp-long gap within a non-coding region could not be sequenced. Each genome contains the standard 36 genes (atp8 is missing). G + T content and the degree of GC- and AT-skews of these three mitogenome (and their individual elements) were higher than in other monogeneans. nad2, atp6 and nad6 were the most variable PCGs, whereas cox1, nad1 and cytb were the most conserved. Mitochondrial phylogenomics analysis, conducted using concatenated amino acid sequences of all PCGs, indicates that evolutionary relationships of the three genera are: (Eudiplozoon, (Paradiplozoon, Sindiplozoon)); and of the three suborders: (Discocotylinea, (Microcotylinea, Gastrocotylinea)). These intergeneric relationships were also supported by the skewness and principal component analyses.

CONCLUSIONS: Our results show that nad2, atp6 and nad6 (fast-evolving) would be better candidates than cox1 (slow-evolving) for species identification and population genetics studies in Diplozoidae. Nucleotide bias and codon and amino acid usage patterns of the three diplozoid mitogenomes are more similar to cestodes and trematodes than to other monogenean flatworms. This unusual mutational bias was reflected in disproportionately long branches in the phylogram. Our study offsets the scarcity of molecular data for the subclass Polyopisthocotylea to some extent, and might provide important new insights into the evolutionary history of the three genera and three suborders.}, } @article {pmid30176800, year = {2018}, author = {Jiang, BL and Jiang, GF and Liu, W and Yang, LC and Yang, LY and Wang, L and Hang, XH and Tang, JL}, title = {RpfC regulates the expression of the key regulator hrpX of the hrp/T3SS system in Xanthomonas campestris pv. campestris.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {103}, pmid = {30176800}, issn = {1471-2180}, abstract = {BACKGROUND: The Gram-negative phytopathogenic bacterium Xanthomonas campestris pv. campestris recruits the hrp/T3SS system to inject pathogenicity effector proteins into host cells and uses the rpf/DSF cell-cell signaling system to regulate the expression of virulence factors such as extracellular enzymes and polysaccharide. Whether these two systems have any connection is unknown.

METHODS: Positive regulator candidates affecting hrpX expression were identified by sacB strategy. The transcriptional expression was determined by qRT-PCR and GUS activity analysis. Transcriptome analysis was performed by RNA deep-sequencing. The hypersensitive response (HR) was determined in the nonhost plant pepper ECW-10R and electrolyte leakage assay.

RESULTS: Mutation of the gene encoding the sensor RpfC of the rpf/DSF system significantly reduced the expression of hrpX, the key regulator of the hrp/T3SS system, all of the genes in the hrp cluster and most reported type III effector genes. Mutation of rpfG did not affect the expression of hrpX. The rpfC mutant showed a delayed and weakened HR induction.

CONCLUSIONS: RpfC positively regulates the expression of hrpX independent of RpfG, showing a complex regulatory network linking the rpf/DSF and hrp/T3SS systems.}, } @article {pmid30176798, year = {2018}, author = {Wei, J and Guo, X and Liu, H and Chen, Y and Wang, W}, title = {The variation profile of intestinal microbiota in blunt snout bream (Megalobrama amblycephala) during feeding habit transition.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {99}, pmid = {30176798}, issn = {1471-2180}, abstract = {BACKGROUND: The blunt snout bream (Megalobrama amblycephala) is one of the most important commercial herbivorous fish in China, and dietary transition is an important event in blunt snout bream development. Gut microbiota has a vital role to host animal. However, little was known about the relationship among feeding habits transition, gut microbiota and digestive enzymes of gut content.

RESULTS: In this study, 186,328 high-quality reads from nine 16S rRNA libraries were obtained using the Illumina MiSeq PE300 platform. The valid sequences were classified into 388 Operational Taxonomic Units, and a total of 223 genera, belonging to 20 phyla, were identified. The clustering result of gut bacterial communities is consistently related to the clustering result of intestinal content compositions. Proteobacteria and Firmicutes constitute the 'core' gut microbiota of blunt snout bream. Cetobacterium and Rhizobium were identified as microbiological markers of gut microbiota at zooplankton-based diet stages and diet transition stages, respectively. Moreover, thirteen potential cellulose-degrading bacteria were detected in our study. The canonical redundancy analysis (RDA) revealed that the feeding habits strongly influenced the gut microbiota and the digestive enzyme activities of gut content, while the result of PICRUSt test suggests that the metabolic capacity of gut microbiota was affected by feeding habit.

CONCLUSIONS: This study provided a comprehensive survey of the gut microbiota in blunt snout bream during its dietary transition period for the first time and clearly showed that the gut microbiota was strongly affected by feeding habit. This work allows us to better understand the relationship among gut microbiota, nutrition metabolism and feeding habits in vertebrate. Further, our study provides a reference for future studies investigating the metabolic adaption of herbivorous fish to shift to a vegetarian diet during their life history.}, } @article {pmid30176795, year = {2018}, author = {Zhang, Y and Tang, D and Lin, X and Ding, M and Tong, Z}, title = {Genome-wide identification of MADS-box family genes in moso bamboo (Phyllostachys edulis) and a functional analysis of PeMADS5 in flowering.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {176}, pmid = {30176795}, issn = {1471-2229}, support = {No. 31270715//National Natural Science Foundation of China/ ; No.31000295//National Natural Science Foundation of China/ ; No. 2012CB723008//Department of S and T for Social Development/ ; No. 2012C12908-2//Zhejiang Provincial Specialized Research Fund for Bamboo Breeding/ ; KF201304//Top Key Discipline of Forestry of Zhejiang Province/ ; }, mesh = {Computational Biology ; Flowers/genetics/*growth & development ; Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; MADS Domain Proteins/*genetics/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Poaceae/*genetics/growth & development/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: MADS-box genes encode a large family of transcription factors that play significant roles in plant growth and development. Bamboo is an important non-timber forest product worldwide, but previous studies on the moso bamboo (Phyllostachys edulis) MADS-box gene family were not accurate nor sufficiently detailed.

RESULTS: Here, a complete genome-wide identification and characterization of the MADS-box genes in moso bamboo was conducted. There was an unusual lack of type-I MADS-box genes in the bamboo genome database (http://202.127.18.221/bamboo/index.php), and some of the PeMADS sequences are fragmented and/or inaccurate. We performed several bioinformatics techniques to obtain more precise sequences using transcriptome assembly. In total, 42 MADS-box genes, including six new type-I MADS-box genes, were identified in bamboo, and their structures, phylogenetic relationships, predicted conserved motifs and promoter cis-elements were systematically investigated. An expression analysis of the bamboo MADS-box genes in floral organs and leaves revealed that several key members are involved in bamboo inflorescence development, like their orthologous genes in Oryza. The ectopic overexpression of one MADS-box gene, PeMADS5, in Arabidopsis triggered an earlier flowering time and the development of an aberrant flower phenotype, suggesting that PeMADS5 acts as a floral activator and is involved in bamboo flowering.

CONCLUSION: We produced the most comprehensive information on MADS-box genes in moso bamboo. Additionally, a critical PeMADS gene (PeMADS5) responsible for the transition from vegetative to reproductive growth was identified and shown to be related to bamboo floral development.}, } @article {pmid30176793, year = {2018}, author = {Yin, M and Wang, X and Ma, X and Gießler, S and Petrusek, A and Griebel, J and Hu, W and Wolinska, J}, title = {Cytonuclear diversity and shared mitochondrial haplotypes among Daphnia galeata populations separated by seven thousand kilometres.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {130}, pmid = {30176793}, issn = {1471-2148}, support = {31670380//National Natural Science Foundation of China/International ; 16ZR1402900//Natural Science Foundation of Shanghai/International ; WO 1587/6-1//German Science Foundation/International ; }, mesh = {Alleles ; Animals ; Bayes Theorem ; Cell Nucleus/*genetics ; China ; DNA/genetics ; DNA, Mitochondrial/genetics ; Daphnia/*genetics ; Europe ; Genes, Mitochondrial ; *Genetic Variation ; Genetics, Population ; Geography ; Haplotypes/*genetics ; Microsatellite Repeats/genetics ; Mitochondria/*genetics ; Phylogeny ; Zooplankton/genetics ; }, abstract = {BACKGROUND: The zooplanktonic cladocerans Daphnia, present in a wide range of water bodies, are an important component of freshwater ecosystems. In contrast to their high dispersal capacity through diapausing eggs carried by waterfowl, Daphnia often exhibit strong population genetic differentiation. Here, to test for common patterns in the population genetic structure of a widespread Holarctic species, D. galeata, we genotyped two sets of populations collected from geographically distant areas: across 13 lakes in Eastern China and 14 lakes in Central Europe. The majority of these populations were genotyped at two types of markers: a mitochondrial gene (for 12S rRNA) and 15 nuclear microsatellite loci.

RESULTS: Mitochondrial DNA demonstrated relatively shallow divergence within D. galeata, with distinct haplotype compositions in the two study regions but one widely distributed haplotype shared between several of the Chinese as well as European populations. At microsatellite markers, clear separation was observed at both large (between China and Europe) and small (within Europe) geographical scales, as demonstrated by Factorial Correspondence Analyses, Bayesian assignment and a clustering method based on genetic distances. Genetic diversity was comparable between the sets of Chinese and European D. galeata populations for both types of markers. Interestingly, we observed a significant association between genetic distance and geographical distance for D. galeata populations in China but not in Europe.

CONCLUSIONS: Our results indicate relatively recent spread of D. galeata across wide expanses of the Palaearctic, with one mtDNA lineage of D. galeata successfully establishing over large distances. Despite a clear differentiation of Chinese and European D. galeata at a nuclear level, the pattern of genetic variation is nevertheless similar between both regions. Overall, our findings provide insights into the genetic population structure of a cladoceran species with extremely wide geographical range.}, } @article {pmid30176792, year = {2018}, author = {Pillai, SE and Kumar, C and Patel, HK and Sonti, RV}, title = {Overexpression of a cell wall damage induced transcription factor, OsWRKY42, leads to enhanced callose deposition and tolerance to salt stress but does not enhance tolerance to bacterial infection.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {177}, pmid = {30176792}, issn = {1471-2229}, support = {SB/S2/JCB-12/2014//Department of Science and Technology, India/ ; PMSI//Council of Scientific and Industrial Research/ ; }, mesh = {Arabidopsis/genetics/immunology ; Cell Wall/physiology ; *Gene Expression Regulation, Plant ; Glucans/*metabolism ; Oryza/*genetics/immunology ; Plant Immunity/*genetics ; Plant Proteins/*genetics/immunology ; Plants, Genetically Modified/genetics/immunology ; *Salt Tolerance ; Stress, Physiological ; Transcription Factors/*genetics/immunology ; }, abstract = {BACKGROUND: Members of the WRKY gene family play important roles in regulating plant responses to abiotic and biotic stresses. Treatment with either one of the two different cell wall degrading enzymes (CWDEs), LipaseA and CellulaseA, induces immune responses and enhances the expression of OsWRKY42 in rice. However, the role of OsWRKY42 in CWDE induced immune responses is not known.

RESULTS: Expression of the rice transcription factor OsWRKY42 is induced upon treatment of rice leaves with CWDEs, wounding and salt. Overexpression of OsWRKY42 leads to enhanced callose deposition in rice and Arabidopsis but this does not enhance tolerance to bacterial infection. Upon treatment with NaCl, Arabidopsis transgenic plants expressing OsWRKY42 exhibited high levels of anthocyanin and displayed enhanced tolerance to salt stress. Treatment with either cellulase or salt induced the expression of several genes involved in JA biosynthesis and response in Arabidopsis. Ectopic expression of OsWRKY42 results in reduced expression of cell wall damage and salt stress induced jasmonic acid biosynthesis and response genes. OsWRKY42 expressing Arabidopsis lines exhibited enhanced tolerance to methyl jasmonate mediated growth inhibition.

CONCLUSION: The results presented here suggest that OsWRKY42 regulates plant responses to either cell wall damage or salinity stress by acting as a negative regulator of jasmonic acid mediated responses.}, } @article {pmid30176658, year = {2018}, author = {Naimoli, V and Donnelly-Greenberg, J and Gabel, NM and Libby, DJ and Panigrosso, ER and Rhindress, K and Powers, AS}, title = {The Role of Acetylcholine in Attention in Turtles (Chrysemys picta).}, journal = {Brain, behavior and evolution}, volume = {92}, number = {1-2}, pages = {71-81}, doi = {10.1159/000492052}, pmid = {30176658}, issn = {1421-9743}, abstract = {Research on mammals and turtles has suggested that acetylcholine is involved in attention in these groups. Two experiments investigated the ability of painted turtles (Chrysemys picta) to ignore irrelevant stimuli when the basal forebrain acetylcholine system was compromised. In experiment 1, turtles given lesions of the basal magnocellular cholinergic nucleus (NBM) or sham lesions were tested on a go/no go discrimination between horizontal and vertical stripes with or without irrelevant inserts in the box. The irrelevant inserts were blue and white checked walls and green carpet on the floor. The group with lesions of the NBM and no irrelevant inserts had no difficulty learning the task, but the lesioned group with irrelevant inserts was impaired on the discrimination. The sham-lesioned group was not impaired by the presence of irrelevant inserts. In experiment 2, turtles were given either the acetylcholine muscarinic receptor blocker scopolamine or saline and tested on the same task. The turtles given scopolamine had no difficulty learning the task in the absence of irrelevant inserts, but they were severely impaired when irrelevant inserts were present. The irrelevant inserts did not affect the learning of control turtles given saline. These findings provide evidence that acetylcholine enhances turtles' ability to orient to relevant stimuli and suggest that its role in learning and memory may be to allow animals to orient to the stimuli relevant to a task and to ignore irrelevant stimuli.}, } @article {pmid30175901, year = {2018}, author = {Webster, NB and Palmer, AR}, title = {Connecting pattern to process: Growth of spiral shell sculpture in the gastropod Nucella ostrina (Muricidae: Ocenebrinae).}, journal = {Evolution & development}, volume = {20}, number = {5}, pages = {160-171}, doi = {10.1111/ede.12265}, pmid = {30175901}, issn = {1525-142X}, support = {//Conchologists of America Clench/Turner Award/International ; PGS-DRGPIN 04863//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {Animal Shells/*anatomy & histology/growth & development ; Animals ; Morphogenesis ; Snails/*anatomy & histology/enzymology/*growth & development ; }, abstract = {Shell morphology is a well-suited and underused system to examine the development of novel forms. The three-dimensional structure produced (the shell) is separate from the largely two-dimensional tissue that secretes it (the mantle), allowing us to disentangle the pattern from the process. Despite knowing a great deal about the mechanics of shell secretion (process), and the variety of shell shapes that exist (pattern), no effort has been made to understand how the mantle changes to produce different shell shapes. We investigated this question in the dimorphic snail Nucella ostrina, which exhibits both smooth and ribbed shells to determine how ribs are formed by the mantle. Rib thickenings are produced only in the outer calcitic shell layer and secreted by the distal Outer Mantle Epithelium (OME) with increased acid phosphatase activity. The evenly thick inner aragonitic layers are secreted by the proximal OME which expresses acid phosphatase. Here we show that locally thicker ribs in N. ostrina are produced by changing the dimensions of the distal OME: elongation in the direction of growth and increased cell height. This should increase the amount of shell material secreted, producing locally thicker shell (ribs). Preliminary evidence suggests this mechanism may be widespread in gastropods.}, } @article {pmid30175900, year = {2018}, author = {Raff, R}, title = {A farewell to EVO&DEVO.}, journal = {Evolution & development}, volume = {20}, number = {5}, pages = {131}, doi = {10.1111/ede.12266}, pmid = {30175900}, issn = {1525-142X}, } @article {pmid30175444, year = {2018}, author = {Hellweger, FL}, title = {Heterotrophic substrate specificity in the aquatic environment: The role of microscale patchiness investigated using modelling.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3825-3835}, doi = {10.1111/1462-2920.14397}, pmid = {30175444}, issn = {1462-2920}, abstract = {Recent observations of natural bacterial communities show high genetic diversity in organic carbon uptake systems (microdiversity) and specificity in substrate species taken up. This seemingly contradicts a large body of literature from laboratory experiments under nutrient-limiting conditions, where mixed substrate use is the rule. This apparent discrepancy can be resolved by realizing that bacteria in the natural aquatic environment encounter nutrients as high-concentration patches. They may live in an ecologically nutrient-limiting environment, but they are rarely in a biologically nutrient-limited state. Rather they switch between non-growing and nutrient-replete states. During nutrient-replete growth the metabolism is saturated and assimilating additional substrates does not increase the growth rate, but carrying the assimilation system constitutes a cost. Consequently, the specialist strategy is beneficial, which is consistent with observations from laboratory experiments. When the bacteria are not growing, the added cost also reduces the fitness of the generalist species. A simple mathematical model encompassing the relevant mechanisms is developed and parameterized realistically based on the literature. The model predicts that, under pulsed conditions, specialization is beneficial when the metabolic cost of an additional uptake system is more than ~0.5% of the total metabolic cost, which is a reasonable estimate and illustrates that this is a plausible hypothesis.}, } @article {pmid30173951, year = {2018}, author = {Nogués-Bravo, D and Rodríguez-Sánchez, F and Orsini, L and de Boer, E and Jansson, R and Morlon, H and Fordham, DA and Jackson, ST}, title = {Cracking the Code of Biodiversity Responses to Past Climate Change.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {765-776}, doi = {10.1016/j.tree.2018.07.005}, pmid = {30173951}, issn = {1872-8383}, abstract = {How individual species and entire ecosystems will respond to future climate change are among the most pressing questions facing ecologists. Past biodiversity dynamics recorded in the paleoecological archives show a broad array of responses, yet significant knowledge gaps remain. In particular, the relative roles of evolutionary adaptation, phenotypic plasticity, and dispersal in promoting survival during times of climate change have yet to be clarified. Investigating the paleo-archives offers great opportunities to understand biodiversity responses to future climate change. In this review we discuss the mechanisms by which biodiversity responds to environmental change, and identify gaps of knowledge on the role of range shifts and tolerance. We also outline approaches at the intersection of paleoecology, genomics, experiments, and predictive models that will elucidate the processes by which species have survived past climatic changes and enhance predictions of future changes in biological diversity.}, } @article {pmid30173885, year = {2018}, author = {Sutikna, T and Tocheri, MW and Faith, JT and Jatmiko, and Due Awe, R and Meijer, HJM and Wahyu Saptomo, E and Roberts, RG}, title = {The spatio-temporal distribution of archaeological and faunal finds at Liang Bua (Flores, Indonesia) in light of the revised chronology for Homo floresiensis.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {52-74}, doi = {10.1016/j.jhevol.2018.07.001}, pmid = {30173885}, issn = {1095-8606}, abstract = {Liang Bua, the type site of Homo floresiensis, is a limestone cave on the Indonesian island of Flores with sedimentary deposits currently known to range in age from about 190 thousand years (ka) ago to the present. Recent revision of the stratigraphy and chronology of this depositional sequence suggests that skeletal remains of H. floresiensis are between ∼100 and 60 ka old, while cultural evidence of this taxon occurs until ∼50 ka ago. Here we examine the compositions of the faunal communities and stone artifacts, by broad taxonomic groups and raw materials, throughout the ∼190 ka time interval preserved in the sequence. Major shifts are observed in both the faunal and stone artifact assemblages that reflect marked changes in paleoecology and hominin behavior, respectively. Our results suggest that H. floresiensis and Stegodon florensis insularis, along with giant marabou stork (Leptoptilos robustus) and vulture (Trigonoceps sp.), were likely extinct by ∼50 ka ago. Moreover, an abrupt and statistically significant shift in raw material preference due to an increased use of chert occurs ∼46 thousand calibrated radiocarbon (14C) years before present (ka cal. BP), a pattern that continues through the subsequent stratigraphic sequence. If an increased preference for chert does, in fact, characterize Homo sapiens assemblages at Liang Bua, as previous studies have suggested (e.g., Moore et al., 2009), then the shift observed here suggests that modern humans arrived on Flores by ∼46 ka cal. BP, which would be the earliest cultural evidence of modern humans in Indonesia.}, } @article {pmid30173884, year = {2018}, author = {Simons, EA and Frost, SR and Singleton, M}, title = {Ontogeny and phylogeny of the cercopithecine cranium: A geometric morphometric approach to comparing shape change trajectories.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {40-51}, doi = {10.1016/j.jhevol.2018.08.001}, pmid = {30173884}, issn = {1095-8606}, abstract = {While the analysis of ontogenetic trajectories is common in geometric morphometrics (GM), the simultaneous comparison of several trajectories can be unwieldy and is, in some cases, unable to make use of one of the main advantages of GM, visualization. Furthermore, due to the paucity of the paleontological record, analyses of trajectories are often limited to extant taxa. We address these issues by presenting a method for visualizing the similarities and differences of cranial ontogenetic trajectories among taxa and a method for reconstructing ancestral ontogenetic trajectories, so that these differences can be investigated in a phylogenetic context. We also tested for the presence of phylogenetic signal in the ontogenetic trajectories themselves. Using an ontogenetic series of 522 crania, representing 17 cercopithecine species from 8 genera, we first calculated ontogenetic trajectories of cranial shape change for each species, and then entered these trajectories into a principal components analysis to produce a developmental shape-change trajectory PCA (δPCA). Then, through an augmentation of the phylomorphospace approach, we projected a molecular phylogeny onto the major axes of trajectory shape variation from the δPCA to produce an 'ontophylomorphospace,' using squared-change parsimony to reconstruct interior nodes. Through these procedures, we were able to determine that the δPCAs illustrate patterns of variation in these developmental trajectories in a visually intuitive manner that allows for easier comparisons among taxa. Through examination of the ontophylomorphospace, we found that African papionins exhibit extensive homoplasy in the evolution of cranial ontogenetic trajectories, and that Asian species of Macaca show highly derived ontogenetic trajectories relative to other cercopithecines. Additionally, we found no support for the presence of a phylogenetic signal in cranial ontogenetic trajectories. The δPCA and the ontophylomorphospace are ways in which to visualize and compare complex, multivariate shape transformations, both among extant taxa and over evolutionary time, respectively.}, } @article {pmid30173883, year = {2018}, author = {Aubert, M and Brumm, A and Huntley, J}, title = {Early dates for 'Neanderthal cave art' may be wrong.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {215-217}, doi = {10.1016/j.jhevol.2018.08.004}, pmid = {30173883}, issn = {1095-8606}, } @article {pmid30173869, year = {2018}, author = {Hashikawa, K and Hashikawa, Y and Lischinsky, J and Lin, D}, title = {The Neural Mechanisms of Sexually Dimorphic Aggressive Behaviors.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {10}, pages = {755-776}, doi = {10.1016/j.tig.2018.07.001}, pmid = {30173869}, issn = {0168-9525}, abstract = {Aggression is a fundamental social behavior that is essential for competing for resources and protecting oneself and families in both males and females. As a result of natural selection, aggression is often displayed differentially between the sexes, typically at a higher level in males than females. Here, we highlight the behavioral differences between male and female aggression in rodents. We further outline the aggression circuits in males and females, and compare their differences at each circuit node. Lastly, we summarize our current understanding regarding the generation of sexually dimorphic aggression circuits during development and their maintenance during adulthood. In both cases, gonadal steroid hormones appear to play crucial roles in differentiating the circuits by impacting on the survival, morphology, and intrinsic properties of relevant cells. Many other factors, such as environment and experience, may also contribute to sex differences in aggression and remain to be investigated in future studies.}, } @article {pmid30173665, year = {2018}, author = {Lucena, D and Mauri, M and Schmidt, F and Eckhardt, B and Graumann, PL}, title = {Microdomain formation is a general property of bacterial membrane proteins and induces heterogeneity of diffusion patterns.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {97}, pmid = {30173665}, issn = {1741-7007}, abstract = {BACKGROUND: Proteins within the cytoplasmic membrane display distinct localization patterns and arrangements. While multiple models exist describing the dynamics of membrane proteins, to date, there have been few systematic studies, particularly in bacteria, to evaluate how protein size, number of transmembrane domains, and temperature affect their diffusion, and if conserved localization patterns exist.

RESULTS: We have used fluorescence microscopy, single-molecule tracking (SMT), and computer-aided visualization methods to obtain a better understanding of the three-dimensional organization of bacterial membrane proteins, using the model bacterium Bacillus subtilis. First, we carried out a systematic study of the localization of over 200 B. subtilis membrane proteins, tagged with monomeric mVenus-YFP at their original gene locus. Their subcellular localization could be discriminated in polar, septal, patchy, and punctate patterns. Almost 20% of membrane proteins specifically localized to the cell poles, and a vast majority of all proteins localized in distinct structures, which we term microdomains. Dynamics were analyzed for selected membrane proteins, using SMT. Diffusion coefficients of the analyzed transmembrane proteins did not correlate with protein molecular weight, but correlated inversely with the number of transmembrane helices, i.e., transmembrane radius. We observed that temperature can strongly influence diffusion on the membrane, in that upon growth temperature upshift, diffusion coefficients of membrane proteins increased and still correlated inversely to the number of transmembrane domains, following the Saffman-Delbrück relation.

CONCLUSIONS: The vast majority of membrane proteins localized to distinct multimeric assemblies. Diffusion of membrane proteins can be suitably described by discriminating diffusion coefficients into two protein populations, one mobile and one immobile, the latter likely constituting microdomains. Our results show there is high heterogeneity and yet structural order in the cell membrane, and provide a roadmap for our understanding of membrane organization in prokaryotes.}, } @article {pmid30172862, year = {2018}, author = {Tritten, L and Geary, TG}, title = {Helminth extracellular vesicles in host-parasite interactions.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {73-79}, doi = {10.1016/j.mib.2018.08.002}, pmid = {30172862}, issn = {1879-0364}, abstract = {Extracellular vesicles (EVs) have been characterized from many species of parasitic helminths, and recent experimental evidence supports important functions for their cargo in host-parasite relationships as immunomodulatory mediators. Here we summarize available data on the effects of parasite-derived EVs, including their protein and/or small RNA contents, on their hosts.}, } @article {pmid30172257, year = {2018}, author = {Sovran, B and Planchais, J and Jegou, S and Straube, M and Lamas, B and Natividad, JM and Agus, A and Dupraz, L and Glodt, J and Da Costa, G and Michel, ML and Langella, P and Richard, ML and Sokol, H}, title = {Enterobacteriaceae are essential for the modulation of colitis severity by fungi.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {152}, pmid = {30172257}, issn = {2049-2618}, abstract = {BACKGROUND: Host-microbe balance maintains intestinal homeostasis and strongly influences inflammatory conditions such as inflammatory bowel diseases (IBD). Here we focused on bacteria-fungi interactions and their implications on intestinal inflammation, a poorly understood area.

METHODS: Dextran sodium sulfate (DSS)-induced colitis was assessed in mice treated with vancomycin (targeting gram-positive bacteria) or colistin (targeting Enterobacteriaceae) and supplemented with either Saccharomyces boulardii CNCM I-745 or Candida albicans. Inflammation severity as well as bacterial and fungal microbiota compositions was monitored.

RESULTS: While S. boulardii improved DSS-induced colitis and C. albicans worsened it in untreated settings, antibiotic treatment strongly modified DSS susceptibility and effects of fungi on colitis. Vancomycin-treated mice were fully protected from colitis, while colistin-treated mice retained colitis phenotype but were not affected anymore by administration of fungi. Antibacterial treatments not only influenced bacterial populations but also had indirect effects on fungal microbiota. Correlations between bacterial and fungal relative abundance were dramatically decreased in colistin-treated mice compared to vancomycin-treated and control mice, suggesting that colistin-sensitive bacteria are involved in interactions with fungi. Restoration of the Enterobacteriaceae population by administrating colistin-resistant Escherichia coli reestablished both beneficial effects of S. boulardii and pathogenic effects of C. albicans on colitis severity. This effect was at least partly mediated by an improved gut colonization by fungi.

CONCLUSIONS: Fungal colonization of the gut is affected by the Enterobacteriaceae population, indirectly modifying effects of mycobiome on the host. This finding provides new insights into the role of inter-kingdom functional interactions in intestinal physiopathology and potentially in IBD.}, } @article {pmid30172254, year = {2018}, author = {Lager, S and de Goffau, MC and Sovio, U and Peacock, SJ and Parkhill, J and Charnock-Jones, DS and Smith, GCS}, title = {Detecting eukaryotic microbiota with single-cell sensitivity in human tissue.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {151}, pmid = {30172254}, issn = {2049-2618}, support = {MR/K021133/1//Medical Research Council/United Kingdom ; G1100221//Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, abstract = {BACKGROUND: Fetal growth restriction, pre-eclampsia, and pre-term birth are major adverse pregnancy outcomes. These complications are considerable contributors to fetal/maternal morbidity and mortality worldwide. A significant proportion of these cases are thought to be due to dysfunction of the placenta. However, the underlying mechanisms of placental dysfunction are unclear. The aim of the present study was to investigate whether adverse pregnancy outcomes are associated with evidence of placental eukaryotic infection.

RESULTS: We modified the 18S Illumina Amplicon Protocol of the Earth Microbiome Project and made it capable of detecting just a single spiked-in genome copy of Plasmodium falciparum, Saccharomyces cerevisiae, or Toxoplasma gondii among more than 70,000 human cells. Using this method, we were unable to detect eukaryotic pathogens in placental biopsies in instances of adverse pregnancy outcome (n = 199) or in healthy controls (n = 99).

CONCLUSIONS: Eukaryotic infection of the placenta is not an underlying cause of the aforementioned pregnancy complications. Possible clinical applications for this non-targeted, yet extremely sensitive, eukaryotic screening method are manifest.}, } @article {pmid30172106, year = {2018}, author = {Becker, J and Wittmann, C}, title = {From systems biology to metabolically engineered cells-an omics perspective on the development of industrial microbes.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {180-188}, doi = {10.1016/j.mib.2018.06.001}, pmid = {30172106}, issn = {1879-0364}, abstract = {Green routes are indispensable for a sustainable production of energy, chemicals and materials, and health and nutrition products from renewable resources. Naturally, microbes are capable to conduct many of the desired biochemical conversions involved, however, only at rather low efficiency. It is therefore essential to metabolically engineer them towards efficient cell factories, which enable a high product titer, yield and productivity, exhibit a good process robustness and a broad substrate spectrum, and are safe to be used, to name a few prominent points from the wish list for industrial bio-production. Such optimization of a microbial cell typically involves the implementation of several up to multiple traits into its genome, which then mediate the desired phenotype. While the genetic modification step itself is straightforward due to the much advanced genome editing methods, the selection of what exactly has to be optimized out of the manifold possibilities is still a challenge. Here we will discuss, how systems biology can offer guidance to orchestrate the hundreds to thousands of biochemical conversions of a microbe into a concert of desired performance. To this end, we will highlight recent success stories, where systems biology approaches have enabled next-level cell factories and bioprocesses.}, } @article {pmid30172010, year = {2018}, author = {Pepato, AR and Vidigal, THDA and Klimov, PB}, title = {Molecular phylogeny of marine mites (Acariformes: Halacaridae), the oldest radiation of extant secondarily marine animals.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {182-188}, doi = {10.1016/j.ympev.2018.08.012}, pmid = {30172010}, issn = {1095-9513}, abstract = {The family Halacaridae comprises more than one thousand mostly marine or rarely freshwater species. Many are predacious, but among marine mites, some genera evolved the ability to feed on macroalgae. We inferred a time-calibrated phylogeny based on 18S rDNA, 28S rDNA, and Cytochrome oxidase I (5,143 nt aligned) and all non-monotypic halacarid subfamilies plus a representative outgroup set (72 taxa). The family Halacaridae was rendered as the sister-group of Parasitengona, diverging 321.5, 264.0-381.3 Ma and radiating 271.3, 221.7-324.2 Ma (median, HPD). Thus, marine mites represent the oldest known extant animal lineage that secondarily invaded the sea, with the marine turtles being the second oldest such lineage (crown group 212.3, 194.9-231.4 Ma). Two freshwater mite lineages, represented by Limnohalacarus (219.2, 165.9-274.6) and Porohalacarus (175.3, 118.5-233.1), were inferred mutually non-monophyletic, suggesting two independent invasions to freshwater. The conventional subfamily Rhombognathinae (macroalgae feeders) was not recovered as monophyletic, with Metarhombognathus-Rhombognathides, restricted to the Northern Hemisphere, originating 177.5, 134.8-223.3 Ma and diversifying 88.3, 32.7-152.3 Ma. This is congruent to a previous hypothesis of their northern origin prior to the opening of the Norwegian Sea (58 Ma). Our phylogeny indicates the need for reclassification of the traditional subfamilies and suggests that previous molecular results (e.g., Rhombognathus deeply nested in Copidognathinae) is an analytical artifact due to a chimeric sequence.}, } @article {pmid30172009, year = {2018}, author = {Pavón-Vázquez, CJ and García-Vázquez, UO and Bryson, RW and Feria-Ortiz, M and Manríquez-Morán, NL and de Oca, AN}, title = {Integrative species delimitation in practice: Revealing cryptic lineages within the short-nosed skink Plestiodon brevirostris (Squamata: Scincidae).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {242-257}, doi = {10.1016/j.ympev.2018.08.020}, pmid = {30172009}, issn = {1095-9513}, abstract = {Integrative taxonomy has been generally considered as a goal in systematics for more than a decade. Here, we employed environmental, molecular, and morphological data to evaluate the species boundaries within the short-nosed skink Plestiodon brevirostris from south-central Mexico, one member of the morphologically conservative P. brevirostris group. Our molecular dataset includes one mitochondrial and two nuclear loci. The mitochondrial fragment includes the full length of the gene coding for the NADH dehydrogenase subunit 1 protein, a segment of the gene coding for 16S ribosomal RNA, and flanking tRNAs. The nuclear dataset includes fragments of the genes coding for the megakaryoblastic leukemia 1 and RNA fingerprint 35 proteins. We employed phylogenetic reconstruction, analyses of population structure and morphological variation, and species delimitation methods (including the integration of the three kinds of data in a unified probabilistic framework) to evaluate species limits. Our results suggest that P. brevirostris represents four distinct species. The information provided by each kind of data allowed us to discern between alternative explanations for the observed patterns of geographic structure. Two of the newly recognized lineages are poorly differentiated morphologically but apparently differ in environmental preferences and are allopatric. Additionally, one lineage is microendemic and parapatric with respect to another one. Moreover, our phylogenetic analyses suggest that other taxa within the P. brevirostris group may represent species complexes. We discuss our results in the context of integrative species delimitation.}, } @article {pmid30172008, year = {2018}, author = {Mandák, B and Krak, K and Vít, P and Lomonosova, MN and Belyayev, A and Habibi, F and Wang, L and Douda, J and Štorchová, H}, title = {Hybridization and polyploidization within the Chenopodium album aggregate analysed by means of cytological and molecular markers.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {189-201}, doi = {10.1016/j.ympev.2018.08.016}, pmid = {30172008}, issn = {1095-9513}, abstract = {Hybridization and polyploidization represent an important speciation mechanism in the diploid-polyploid complex of the Chenopodium album aggregate. In the present study we successfully reconstructed the evolutionary histories of the majority of Eurasian representatives of the C. album aggregate, resulting in the most comprehensive phylogenetic analysis of this taxonomically intricate group of species to date. We applied a combination of classical karyology for precise chromosome number determination, genomic in-situ hybridization for the determination of genomic composition, flow cytometry for the estimation of genome size and sequencing of plastid (cpDNA) and nuclear (ribosomal internal transcribed spacer - ITS and the introns of the FLOWERING LOCUS T LIKE genes - FTL) markers for a phylogenetic reconstruction and the identification of parental genomes in polyploid taxa. The FTL markers identified eight well supported evolutionary lineages. Five of them include at least one diploid species, and the remaining three comprise solely the subgenomes of polyploids that probably represent extinct or unknown diploid taxa. The existence of eight basic diploid lineages explains the origin of seven Eurasian polyploid groups and brings evidence of a nearly unlimited number of subgenomic combinations. The supposed promiscuity generated new species wherever different diploid lineages met each other and gave rise to tetraploid species or whenever they met other tetraploid species to produce hexaploid species throughout their evolutionary history. Finally, we unravelled a surprisingly simple scheme of polyploid species formation within the C. album aggregate. We determined seven groups of polyploid species differing in their origin in either Eurasia or Africa and convincingly demonstrated that (1) all Chenopodium polyploid species under study are of allopolyploid origin, (2) there are eight major monophyletic evolutionary lineages represented by extant or extinct/unknown diploid taxa, (3) those monophyletic lineages represent individual subgenomes, (4) hybridization among the lineages created seven subgenomic combinations of polyploid taxa, (5) taxa represented by particular subgenome combinations were further subjected to diversification, and (6) the majority of species are relatively young, not exceeding the age of the Quaternary period.}, } @article {pmid30171849, year = {2018}, author = {Bondurand, N and Dufour, S and Pingault, V}, title = {News from the endothelin-3/EDNRB signaling pathway: Role during enteric nervous system development and involvement in neural crest-associated disorders.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.08.014}, pmid = {30171849}, issn = {1095-564X}, abstract = {The endothelin system is a vertebrate-specific innovation with important roles in regulating the cardiovascular system and renal and pulmonary processes, as well as the development of the vertebrate-specific neural crest cell population and its derivatives. This system is comprised of three structurally similar 21-amino acid peptides that bind and activate two G-protein coupled receptors. In 1994, knockouts of the Edn3 and Ednrb genes revealed their crucial function during development of the enteric nervous system and melanocytes, two neural-crest derivatives. Since then, human and mouse genetics, combined with cellular and developmental studies, have helped to unravel the role of this signaling pathway during development and adulthood. In this review, we will summarize the known functions of the EDN3/EDNRB pathway during neural crest development, with a specific focus on recent scientific advances, and the enteric nervous system in normal and pathological conditions.}, } @article {pmid30171169, year = {2018}, author = {Duyvesteyn, HME and Kotecha, A and Ginn, HM and Hecksel, CW and Beale, EV and de Haas, F and Evans, G and Zhang, P and Chiu, W and Stuart, DI}, title = {Machining protein microcrystals for structure determination by electron diffraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9569-9573}, pmid = {30171169}, issn = {1091-6490}, support = {090532/Z/09/Z//Wellcome Trust/United Kingdom ; 206422/Z/17/Z//Wellcome Trust/United Kingdom ; ALR00040//Wellcome Trust/United Kingdom ; P41 GM103832/GM/NIGMS NIH HHS/United States ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; 101122/Z/13/Z//Wellcome Trust/United Kingdom ; MR/N00065X/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; ALR00750-B500.1//Wellcome Trust/United Kingdom ; }, mesh = {Cryoelectron Microscopy/methods ; Crystallography, X-Ray/instrumentation/*methods ; Electrons ; Ions ; Microtechnology/instrumentation/*methods ; Muramidase/chemistry/*ultrastructure ; Synchrotrons ; }, abstract = {We demonstrate that ion-beam milling of frozen, hydrated protein crystals to thin lamella preserves the crystal lattice to near-atomic resolution. This provides a vehicle for protein structure determination, bridging the crystal size gap between the nanometer scale of conventional electron diffraction and micron scale of synchrotron microfocus beamlines. The demonstration that atomic information can be retained suggests that milling could provide such detail on sections cut from vitrified cells.}, } @article {pmid30171168, year = {2018}, author = {Long, B and Yu, CP and Konkle, T}, title = {Mid-level visual features underlie the high-level categorical organization of the ventral stream.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E9015-E9024}, pmid = {30171168}, issn = {1091-6490}, mesh = {Adult ; Brain Mapping/methods ; Female ; Functional Neuroimaging/methods ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging/methods ; Male ; *Models, Neurological ; Pattern Recognition, Visual/*physiology ; Photic Stimulation/methods ; Visual Cortex/*physiology ; Visual Pathways/*physiology ; Young Adult ; }, abstract = {Human object-selective cortex shows a large-scale organization characterized by the high-level properties of both animacy and object size. To what extent are these neural responses explained by primitive perceptual features that distinguish animals from objects and big objects from small objects? To address this question, we used a texture synthesis algorithm to create a class of stimuli-texforms-which preserve some mid-level texture and form information from objects while rendering them unrecognizable. We found that unrecognizable texforms were sufficient to elicit the large-scale organizations of object-selective cortex along the entire ventral pathway. Further, the structure in the neural patterns elicited by texforms was well predicted by curvature features and by intermediate layers of a deep convolutional neural network, supporting the mid-level nature of the representations. These results provide clear evidence that a substantial portion of ventral stream organization can be accounted for by coarse texture and form information without requiring explicit recognition of intact objects.}, } @article {pmid30171167, year = {2018}, author = {Ramesh, R}, title = {Defect engineering using crystal symmetry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9344-9346}, pmid = {30171167}, issn = {1091-6490}, mesh = {*Crystallography, X-Ray ; Engineering ; *Models, Molecular ; Physical Phenomena ; }, } @article {pmid30170783, year = {2018}, author = {Gillings, MR and Westoby, M and Ghaly, TM}, title = {Pollutants That Replicate: Xenogenetic DNAs.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {975-977}, doi = {10.1016/j.tim.2018.08.003}, pmid = {30170783}, issn = {1878-4380}, abstract = {Pollution is the dissemination of material that has harmful effects. Mobile DNA elements and antibiotic-resistance genes are being disseminated into the environment via human activity, and are increasingly being viewed as serious pollutants. These pollutants differ from conventional contaminants in important ways: they can replicate, and they can evolve.}, } @article {pmid30170625, year = {2018}, author = {Majeed, MH and Khokhar, MA and Abid, M and Raza, A and Qaisar, MN and Ali, AA and Waqas, A}, title = {Frequency and correlates of symptoms of anxiety and depression among young caregivers of cancer patients: a pilot study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {631}, pmid = {30170625}, issn = {1756-0500}, mesh = {Adolescent ; *Anxiety ; Caregivers/*psychology ; Child ; Cross-Sectional Studies ; *Depression ; Female ; Humans ; Male ; Neoplasms/nursing ; Pakistan ; Pilot Projects ; Reproducibility of Results ; Young Adult ; }, abstract = {OBJECTIVES: To determine the frequency of symptoms of anxiety and depression among the young caregivers of family members with cancer and their correlation with role of gender, age and socio-economic status.

RESULTS: A total of 87.8% of caregivers were between 11 and 16 years of age, with 94.6% reported having support from another caregiver. At least 95% of caregivers reported symptoms of anxiety with a higher predisposition among females. Around 73% of caregivers had low monthly incomes followed by (22.9%) middle and (4.1%) high monthly incomes. Care givers belonging to low income groups were more likely to report anxiety and depressive symptoms (70%). Young adults 17-18 years of age reported fewer symptoms of anxiety (10.9%) than their younger counterparts. Reported symptoms of anxiety and depression decreased when the number of care givers increased-2 (67.5%), 3 (16.2%), 4 (5.4%). Increased hospital stay was associated with increased frequency of symptoms, but not beyond 5 weeks.}, } @article {pmid30170618, year = {2018}, author = {Siddaramappa, S and Pullela, K and Thimmappa, B and Devkota, R and Bajaj, R and Manivannan, B and Mahalingam, N and Pradeep, BE}, title = {Characterization of blaCTX-M sequences of Indian origin and thirteen uropathogenic Escherichia coli isolates resistant to multiple antibiotics.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {630}, pmid = {30170618}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/pharmacology ; Cephalosporins/*pharmacology ; Drug Resistance, Bacterial/*genetics ; Escherichia coli Infections ; Escherichia coli Proteins/*genetics ; Humans ; India ; Sequence Analysis, DNA ; Uropathogenic Escherichia coli/*genetics ; beta-Lactamases ; }, abstract = {OBJECTIVES: ESBL-producing isolates of the Enterobacteriaceae occur throughout the world. The objectives of this study were to characterize uropathogenic Escherichia coli isolated at a tertiary care hospital in southern India, and shed light on blaCTX-M sequences of Indian origin.

RESULTS: A cohort of 13 urinary isolates of E. coli (obtained from patients at the Sri Sathya Sai Institute of Higher Medical Sciences, Prasanthigram, Andhra Pradesh, India) were characterized and found to be resistant to multiple antibiotics, including extended-spectrum cephalosporins. All 13 isolates contained blaCTX-M-15, and many of them transferred this genotype to at least one laboratory strain of E. coli after conjugation. Analyses of blaCTX-M-15 sequences (n = 141) of Indian origin showed that > 85% of them were obtained from bacteria not associated with the urinary tract, and that E. coli isolates account for majority of all blaCTX-M-15-carrying bacteria reported from India. Other types of blaCTX-M appear to be rare in India, since only six such sequences were reported as of July 2015. The results indicate that 'selection pressure' exerted by extended-spectrum cephalosporins may have stabilized the blaCTX-M-15 genotype among E. coli in India. The rarity of other blaCTX-M suggests that they lack the survival advantage that blaCTX-M-15 may have.}, } @article {pmid30170613, year = {2018}, author = {Ssekatawa, K and Byarugaba, DK and Wampande, E and Ejobi, F}, title = {A systematic review: the current status of carbapenem resistance in East Africa.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {629}, pmid = {30170613}, issn = {1756-0500}, mesh = {Acinetobacter baumannii ; Africa, Eastern ; Anti-Bacterial Agents ; Carbapenems/*pharmacology ; *Drug Resistance, Bacterial ; Escherichia coli ; Humans ; Microbial Sensitivity Tests ; beta-Lactamases ; }, abstract = {OBJECTIVE: In this systematic review, we present the molecular epidemiology and knowledge gaps of the carbapenem resistance in East Africa as well as the future probable research interventions that can be used to address the emergence of carbapenem resistance in the region.

RESULTS: The 17 articles which presented concrete information about the prevalence of carbapenem resistance in East Africa were reviewed. Tanzania exhibited the highest level of carbapenem resistance at 35% while DRC had the lowest level at 0.96%. Uganda was the only country with studies documenting CR obtained amongst hospital environment isolates with incidence ranging from 21% in Pseudomonas aeruginosa to 55% in Acinetobacter baumannii. Carbapenem resistance was more exhibited in A. baumannii (23%), followed by P. aeruginosa (17%), Klebsiella pneumoniae (15%), Proteus mirabilis (14%) and Escherichia coli (12%) mainly isolated from respiratory tract, blood, urine and wound/pus. The regional genetic determinants of carbapenem resistance detected were blaIMP, blaVIM-1 blaSPM-l, blaNDM-1, blaOXA-23 blaOXA-24, blaOXA-58 and blaKPC.}, } @article {pmid30170609, year = {2018}, author = {Hashimoto, K and Nishimura, S and Kakinoki, R and Akagi, M}, title = {Treatment of angiomatoid fibrous histiocytoma after unplanned excision: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {628}, pmid = {30170609}, issn = {1756-0500}, mesh = {Biopsy ; Child ; Female ; Histiocytoma, Benign Fibrous/*surgery ; Humans ; Immunohistochemistry ; Neoplasm Recurrence, Local ; Skin Neoplasms/*surgery ; }, abstract = {BACKGROUND: Angiomatoid fibrous histiocytoma (AFH) is a relatively uncommon soft tissue tumor of intermediate biologic potential. It occurs in subcutaneous regions of the extremities or the trunk, usually presenting in children or young adults. This is the first reported case of subcutaneous AFH that developed in the iliac region and was treated with an unplanned resection.

CASE PRESENTATION: An 11-year-old girl noticed a small subcutaneous nodule in the iliac region. As the nodule was asymptomatic, it was observed naturally for a year, after which her parents consulted her doctor due to gradual growth of the nodule. The tumor was resected marginally without biopsy by a non-specialized surgeon. Based on the histology of the resected specimen, the tumor was suspected to be a sarcoma. The patient was referred to our hospital where we reinvestigated the histology of the tumor using immunohistochemistry. After confirming diagnosis of the tumor as an AFH, we undertook additional extensive resection in the iliac region where the tumor had developed. There was no evidence of tumor residue in the resected specimen. It has been 3 years since the operation, and there has been no evidence of recurrence.

CONCLUSION: We treated a case of AFH after unplanned resection. If subcutaneous tumors in the iliac region are detected, a diagnosis of AFH should be considered and a simple resection avoided.}, } @article {pmid30170603, year = {2018}, author = {Diawara, I and Nayme, K and Katfy, K and Barguigua, A and Kettani-Halabi, M and Belabbes, H and Timinouni, M and Zerouali, K and Elmdaghri, N}, title = {Analysis of amino acid motif of penicillin-binding proteins 1a, 2b, and 2x in invasive Streptococcus pneumoniae nonsusceptible to penicillin isolated from pediatric patients in Casablanca, Morocco.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {632}, pmid = {30170603}, issn = {1756-0500}, mesh = {*Amino Acid Motifs ; Bacterial Proteins ; Child ; Humans ; Microbial Sensitivity Tests ; Morocco ; Penicillin-Binding Proteins/*genetics ; Penicillins ; Streptococcus pneumoniae/drug effects/*genetics ; }, abstract = {OBJECTIVES: This study aimed to investigate the nature of the amino acid motifs found in PBPs of Streptococcus pneumoniae isolates in invasive diseases from pediatric patients at Casablanca, Morocco. Five penicillin-susceptible (PSSP), ten penicillin-intermediate (PISP), and fifteen penicillin-resistant S. pneumoniae (PRSP) were studied by PCR-RFLP and DNA sequencing of the pbp1a, - 2b, and - 2x genes.

RESULTS: There were no changes in the conserved motifs of PBP1a, PBP2b and PBP2x for PSSP strains. Substitution close to PBP1a conserved motifs were found in all PRSP isolates and six/five PISP. Analysis of PBP2b showed that all but one of the 10 PISP strains and all PRSP had substitutions. Substitution close to PBP2x motifs showed that all but three of the 10 PISP strains and all PRSP had substitutions in tow conserved motifs. A total of 6, 11 and 10 genotypes were found after analysis of pbp1a, pbp2b, and pbp2x, respectively. The penicillin-nonsusceptible S. pneumoniae isolated in Casablanca share most amino acid substitutions of those reported worldwide, but they occurred among pneumococci with low level resistance to b-lactams.}, } @article {pmid30170562, year = {2018}, author = {Rahman, M and Nabi, A and Asadulghani, M and Faruque, SM and Islam, MA}, title = {Toxigenic properties and stx phage characterization of Escherichia coli O157 isolated from animal sources in a developing country setting.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {98}, pmid = {30170562}, issn = {1471-2180}, abstract = {BACKGROUND: In many Asian countries including Bangladesh E. coli O157 are prevalent in animal reservoirs and in the food chain, but the incidence of human infection due to E. coli O157 is rare. One of the reasons could be inability of the organism from animal origin to produce sufficient amount of Shiga toxin (Stx), which is the main virulence factor associated with the severe sequelae of infection. This study aimed to fill out this knowledge gap by investigating the toxigenic properties and characteristics of stx phage of E. coli O157 isolated from animal sources in Bangladesh.

RESULTS: We analysed 47 stx2 positive E. coli O157 of food/animal origin for stx2 gene variants, Shiga toxin production, presence of other virulence genes, stx phage insertion sites, presence of genes associated with functionality of stx phages (Q933 and Q21) and stx2 upstream region. Of the 47 isolates, 46 were positive for both stx2a and stx2d while the remaining isolate was positive for stx2d only. Reverse Passive Latex Agglutination assay (RPLA) showed that 42/47 isolates produced little or no toxin, while 5 isolates produced a high titre of toxin (64 to 128). 39/47 isolates were positive for the Toxin Non-Producing (TNP) specific regions in the stx2 promoter. Additionally, all isolates were negative for antiterminator Q933while a majority of isolates were positive for Q21 gene suggesting the presence of defective stx phage. Of the yehV and wrbA phage insertion sites, yehV was found occupied in 11 isolates while wrbA site was intact in all the isolates. None of the isolates was positive for the virulence gene, cdt but all were positive for hlyA, katP, etpD and eae genes. Isolates that produced high titre Stx (n = 5) produced complete phage particles capable of infecting multiple bacterial hosts. One of these phages was shown to produce stable lysogens in host strains rendering the Stx2 producing ability.

CONCLUSION: Despite low frequency in the tested isolates, E. coli O157 isolates in Bangladesh carry inducible stx phages and have the capacity to produce Stx2, indicating a potential risk of E. coli O157 infection in humans.}, } @article {pmid30170558, year = {2018}, author = {Manohar, P and Nachimuthu, R and Lopes, BS}, title = {The therapeutic potential of bacteriophages targeting gram-negative bacteria using Galleria mellonella infection model.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {97}, pmid = {30170558}, issn = {1471-2180}, abstract = {BACKGROUND: Phage therapy is the therapeutic use of bacteriophages to treat highly drug resistant bacterial infections. The current surge in bacteriophage therapy is motivated mainly because of the emergence of antibiotic-resistant bacteria in clinics. This study evaluated the therapeutic potential of three bacteriophages isolated against Escherichia coli ec311, Klebsiella pneumoniae kp235 and Enterobacter cloacae el140 strains using Galleria mellonella. The in vitro activity of three different phages belonging to Podoviridae and Myoviridae families was studied by the double agar overlay method against multi-drug resistant strains. Larval survivability studies were performed to evaluate the potential of phages against infection using G. mellonella.

RESULTS: All the three phages were found to have potential to infect the host bacterial strains. For in vivo studies it was observed that E. coli and E. cloacae infected larvae, should be treated with three phage doses (20 μL, 104 PFU/mL) at 6 h interval to achieve 100% survival rate. But in the case of K. pneumoniae, a single phage dose treatment showed promising outcome. When mixed bacterial infections (all three bacterial cultures at 108 CFU/mL) were tested, minimum of four doses of phage cocktail (three phages) at 6 h interval was necessary to recover the larvae. All the results were confirmed by enumerating bacteria from the larvae.

CONCLUSION: Our data shows that although in vitro studies showed high infectivity of phages, for in vivo models multiple phage doses were required for effective treatment.}, } @article {pmid30170551, year = {2018}, author = {Liu, M and Ma, Z and Zheng, T and Sun, W and Zhang, Y and Jin, W and Zhan, J and Cai, Y and Tang, Y and Wu, Q and Tang, Z and Bu, T and Li, C and Chen, H}, title = {Insights into the correlation between Physiological changes in and seed development of tartary buckwheat (Fagopyrum tataricum Gaertn.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {648}, pmid = {30170551}, issn = {1471-2164}, support = {31500289//National Natural Science Foundation of China/ ; }, mesh = {Fagopyrum/genetics/*growth & development/physiology ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; High-Throughput Nucleotide Sequencing ; Plant Growth Regulators/metabolism ; Plant Proteins/*genetics ; Seeds/genetics/*growth & development/*physiology ; }, abstract = {BACKGROUND: Tartary buckwheat (Fagopyrum tataricum Gaertn.) is a widely cultivated medicinal and edible crop with excellent economic and nutritional value. The development of tartary buckwheat seeds is a very complex process involving many expression-dependent physiological changes and regulation of a large number of genes and phytohormones. In recent years, the gene regulatory network governing the physiological changes occurring during seed development have received little attention.

RESULTS: Here, we characterized the seed development of tartary buckwheat using light and electron microscopy and measured phytohormone and nutrient accumulation by using high performance liquid chromatography (HPLC) and by profiling the expression of key genes using RNA sequencing with the support of the tartary buckwheat genome. We first divided the development of tartary buckwheat seed into five stages that include complex changes in development, morphology, physiology and phytohormone levels. At the same time, the contents of phytohormones (gibberellin, indole-3-acetic acid, abscisic acid, and zeatin) and nutrients (rutin, starch, total proteins and soluble sugars) at five stages were determined, and their accumulation patterns in the development of tartary buckwheat seeds were analyzed. Second, gene expression patterns of tartary buckwheat samples were compared during three seed developmental stages (13, 19, and 25 days postanthesis, DPA), and 9 765 differentially expressed genes (DEGs) were identified. We analyzed the overlapping DEGs in different sample combinations and measured 665 DEGs in the three samples. Furthermore, expression patterns of DEGs related to phytohormones, flavonoids, starch, and storage proteins were analyzed. Third, we noted the correlation between the trait (physiological changes, nutrient changes) and metabolites during seed development, and discussed the key genes that might be involved in the synthesis and degradation of each of them.

CONCLUSION: We provided abundant genomic resources for tartary buckwheat and Polygonaceae communities and revealed novel molecular insights into the correlations between the physiological changes and seed development of tartary buckwheat.}, } @article {pmid30170550, year = {2018}, author = {Xie, L and Shang, Q}, title = {Genome-wide analysis of purple acid phosphatase structure and expression in ten vegetable species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {646}, pmid = {30170550}, issn = {1471-2164}, mesh = {Acid Phosphatase/*genetics/*metabolism ; Amino Acid Sequence ; *Gene Expression Regulation, Enzymologic ; *Gene Expression Regulation, Plant ; *Genome, Plant ; Glycoproteins/*genetics/*metabolism ; Phylogeny ; Plant Proteins/genetics/metabolism ; Vegetables/enzymology/*genetics ; }, abstract = {BACKGROUND: Acquisition of external phosphorus (P) and optimisation of internal P are essential for plant growth and development, and insufficient availability of P in soils is a major challenge in agriculture. Members of the purple acid phosphatase (PAP) family of enzymes are candidates for increasing P use efficiency. Herein, we identified PAP homologs in the genomes of 10 vegetable species, along with Arabidopsis thaliana and Amborella trichopoda as references, to provide fundamental knowledge for this family.

RESULTS: Phylogenetic analysis of protein sequences revealed nine distinct clades, indicating that functional differentiation of extant PAPs was established prior to the emergence of early angiosperms, and conserved among homologs in each clade. Analysis of transcript abundance in different tissues (root, stem, leaf, flower, and fruit) and following phosphates (Pi) starvation treatments from published RNA-seq transcriptome datasets facilitated comprehensive evaluation of expression patterns, and some groups of tissue-specific and Pi starvation-induced PAPs were characterised. Conserved motifs identified from upstream sequences of homologs that are highly expressed in particular tissues or following starvation treatment suggests that divergence in PAP gene expression is associated with cis-acting elements in promoters.

CONCLUSIONS: The genome-wide analysis of PAP enzyme structure and transcriptional expression patterns advance our understanding of PAP family in vegetables genomes. Therefore, PAP homologs with known enzyme structures and expression profiles could serve as targets for plant breeding and/or genetic engineering programs to improve P acquisition and use.}, } @article {pmid30170543, year = {2018}, author = {Batista, CM and Kessler, RL and Eger, I and Soares, MJ}, title = {Treatment of Trypanosoma cruzi with 2-bromopalmitate alters morphology, endocytosis, differentiation and infectivity.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {19}, pmid = {30170543}, issn = {1471-2121}, mesh = {Animals ; Cell Differentiation/*drug effects ; Cell Survival/drug effects ; Cercopithecus aethiops ; Endocytosis/*drug effects ; Genes, Protozoan ; Inhibitory Concentration 50 ; Life Cycle Stages/drug effects ; Palmitates/*pharmacology ; Palmitic Acid/pharmacology ; Protozoan Proteins/metabolism ; Trypanosoma cruzi/*cytology/drug effects/*pathogenicity/ultrastructure ; Vero Cells ; }, abstract = {BACKGROUND: The palmitate analogue 2-bromopalmitate (2-BP) is a non-selective membrane tethered cysteine alkylator of many membrane-associated enzymes that in the last years emerged as a general inhibitor of protein S-palmitoylation. Palmitoylation is a post-translational protein modification that adds palmitic acid to a cysteine residue through a thioester linkage, promoting membrane localization, protein stability, regulation of enzymatic activity, and the epigenetic regulation of gene expression. Little is known on such important process in the pathogenic protozoan Trypanosoma cruzi, the etiological agent of Chagas disease.

RESULTS: The effect of 2-BP was analyzed on different developmental forms of Trypanosoma cruzi. The IC50/48 h value for culture epimastigotes was estimated as 130 μM. The IC50/24 h value for metacyclic trypomastigotes was 216 nM, while for intracellular amastigotes it was 242 μM and for cell derived trypomasigotes was 262 μM (IC50/24 h). Our data showed that 2-BP altered T. cruzi: 1) morphology, as assessed by bright field, scanning and transmission electron microscopy; 2) mitochondrial membrane potential, as shown by flow cytometry after incubation with rhodamine-123; 3) endocytosis, as seen after incubation with transferrin or albumin and analysis by flow cytometry/fluorescence microscopy; 4) in vitro metacyclogenesis; and 5) infectivity, as shown by host cell infection assays. On the other hand, lipid stress by incubation with palmitate did not alter epimastigote growth, metacyclic trypomastigotes viability or trypomastigote infectivity.

CONCLUSION: Our results indicate that 2-BP inhibits key cellular processes of T. cruzi that may be regulated by palmitoylation of vital proteins and suggest a metacyclic trypomastigote unique target dependency during the parasite development.}, } @article {pmid30170542, year = {2018}, author = {Lower, SE and Stanger-Hall, KF and Hall, DW}, title = {Molecular variation across populations of a widespread North American firefly, Photinus pyralis, reveals that coding changes do not underlie flash color variation or associated visual sensitivity.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {129}, pmid = {30170542}, issn = {1471-2148}, support = {T32 GM007103/GM/NIGMS NIH HHS/United States ; DEB-1311315//National Science Foundation/International ; DEB-0074953//National Science Foundation/International ; T32GM007103/NH/NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Fireflies/*genetics ; Gene Flow ; Gene Frequency/genetics ; Genetic Loci ; *Genetic Variation ; Genetics, Population ; Geography ; Luciferases/genetics ; Open Reading Frames/*genetics ; Pigmentation/*genetics ; Selection, Genetic ; Signal Transduction/genetics ; United States ; Visual Perception/*genetics ; }, abstract = {BACKGROUND: Genes underlying signal production and reception are expected to evolve to maximize signal detection in specific environments. Fireflies vary in their light signal color both within and between species, and thus provide an excellent system in which to study signal production and reception in the context of signaling environments. Differences in signal color have been hypothesized to be due to variation in the sequence of luciferase, the enzyme that catalyzes the light reaction. Similarly, differences in visual sensitivity, which are expected to match signal color, have been hypothesized to be due to variation in the sequence of opsins, the protein component of visual pigments. Here we investigated (1) whether sequence variation in luciferase correlates with variation in signal color and (2) whether sequence variation in opsins correlates with inferred matching visual sensitivity across populations of a widespread North American firefly species, Photinus pyralis. We further tested (3) whether selection has acted on these loci by examining their population-level differentiation relative to the distribution of differentiation derived from a genome-wide sample of loci generated by double-digest RADseq.

RESULTS: We found virtually no coding variation in luciferase or opsins. However, there was extreme divergence in non-coding variation in luciferase across populations relative to a panel of random genomic loci.

CONCLUSIONS: The absence of protein variation at both loci challenges the paradigm that variation in signal color and visual sensitivity in fireflies is exclusively due to coding variation in luciferase and opsin genes. Instead, flash color variation within species must involve other mechanisms, such as abdominal pigmentation or regulation of light organ physiology. Evidence for selection at non-coding variation in luciferase suggests that selection is targeting luciferase regulation and may favor differ expression levels across populations.}, } @article {pmid30170539, year = {2018}, author = {Karnisova, L and Marejkova, M and Hrbackova, H and Mellmann, A and Karch, H and Fruth, A and Drevinek, P and Blahova, K and Bielaszewska, M and Nunvar, J}, title = {Attack of the clones: whole genome-based characterization of two closely related enterohemorrhagic Escherichia coli O26 epidemic lineages.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {647}, pmid = {30170539}, issn = {1471-2164}, support = {194215//Grant Agency of the Charles University/ ; NIPH 75010330//Ministerstvo Zdravotnictví Ceské Republiky (CZ)/ ; 15 28017A//Czech Health Research Council of Ministry of Health of the Czech Republic/ ; ME3205/2-1//German Research Foundation (DFG)/ ; }, mesh = {*Biological Evolution ; DNA, Bacterial ; Enterohemorrhagic Escherichia coli/*classification/genetics/isolation & purification ; Escherichia coli Infections/diagnosis/*epidemiology/microbiology ; *Genetic Variation ; *Genome, Bacterial ; Genomics ; Humans ; Molecular Epidemiology ; Phylogeny ; *Whole Genome Sequencing ; }, abstract = {BACKGROUND: Enterohemorrhagic Escherichia coli (EHEC) O26:H11/H-, the most common non-O157 serotype causing hemolytic uremic syndrome worldwide, are evolutionarily highly dynamic with new pathogenic clones emerging rapidly. Here, we investigated the population structure of EHEC O26 isolated from patients in several European countries using whole genome sequencing, with emphasis on a detailed analysis of strains of the highly virulent new European clone (nEC) which has spread since 1990s.

RESULTS: Genome-wide single nucleotide polymorphism (SNP)-based analysis of 32 EHEC O26 isolated in the Czech Republic, Germany, Austria and Italy demonstrated a split of the nEC (ST29C2 clonal group) into two distinct lineages, which we termed, based on their temporal emergence, as "early" nEC and "late" nEC. The evolutionary divergence of the early nEC and late nEC is marked by the presence of 59 and 70 lineage-specific SNPs (synapomorphic mutations) in the genomes of the respective lineages. In silico analyses of publicly available E. coli O26 genomic sequences identified the late nEC lineage worldwide. Using a PCR designed to target the late nEC synapomorphic mutation in the sen/ent gene, we identified the early nEC decline accompanied by the late nEC rise in Germany and the Czech Republic since 2004 and 2013, respectively. Most of the late nEC strains harbor one of two major types of Shiga toxin 2a (Stx2a)-encoding prophages. The type I stx2a-phage is virtually identical to stx2a-phage of EHEC O104:H4 outbreak strain, whereas the type II stx2a-phage is a hybrid of EHEC O104:H4 and EHEC O157:H7 stx2a-phages and carries a novel mutation in Stx2a. Strains harboring these two phage types do not differ by the amounts and biological activities of Stx2a produced.

CONCLUSIONS: Using SNP-level analyses, we provide the evidence of the evolutionary split of EHEC O26:H11/H- nEC into two distinct lineages, and a recent replacement of the early nEC by the late nEC in Germany and the Czech Republic. PCR targeting the late nEC synapomorphic mutation in ent/sen enables the discrimination of early nEC strains and late nEC strains in clinical and environmental samples, thereby facilitating further investigations of their geographic distribution, prevalence, clinical significance and epidemiology.}, } @article {pmid30169817, year = {2018}, author = {Schneider, AC and Braukmann, T and Banerjee, A and Stefanovic, S}, title = {Convergent Plastome Evolution and Gene Loss in Holoparasitic Lennoaceae.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2663-2670}, pmid = {30169817}, issn = {1759-6653}, abstract = {The Lennoaceae, a small monophyletic plant family of root parasites endemic to the Americas, are one of the last remaining independently evolved lineages of parasitic angiosperms lacking a published plastome. In this study, we present the assembled and annotated plastomes of two species spanning the crown node of Lennoaceae, Lennoa madreporoides and Pholisma arenarium, as well as their close autotrophic relative from the sister family Ehretiaceae, Tiquilia plicata. We find that the plastomes of L. madreporoides and P. arenarium are similar in size and gene content, and substantially reduced compared to T. plicata, consistent with trends seen in other holoparasitic lineages. In particular, most plastid genes involved in photosynthesis function have been lost, whereas housekeeping genes (ribosomal protein-coding genes, rRNAs, and tRNAs) are retained. One notable exception is the persistence of a rbcL open reading frame in P. arenarium but not L. madreporoides suggesting a nonphotosynthetic function for this gene. Of the retained coding genes, dN/dS ratios indicate that some remain under purifying selection, whereas others show relaxed selection. Overall, this study supports the mounting evidence for convergent plastome evolution in flowering plants following the shift to heterotrophy.}, } @article {pmid30169787, year = {2018}, author = {Chiang, CWK and Mangul, S and Robles, C and Sankararaman, S}, title = {A Comprehensive Map of Genetic Variation in the World's Largest Ethnic Group-Han Chinese.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2736-2750}, doi = {10.1093/molbev/msy170}, pmid = {30169787}, issn = {1537-1719}, abstract = {As are most non-European populations, the Han Chinese are relatively understudied in population and medical genetics studies. From low-coverage whole-genome sequencing of 11,670 Han Chinese women we present a catalog of 25,057,223 variants, including 548,401 novel variants that are seen at least 10 times in our data set. Individuals from this data set came from 24 out of 33 administrative divisions across China (including 19 provinces, 4 municipalities, and 1 autonomous region), thus allowing us to study population structure, genetic ancestry, and local adaptation in Han Chinese. We identified previously unrecognized population structure along the East-West axis of China, demonstrated a general pattern of isolation-by-distance among Han Chinese, and reported unique regional signals of admixture, such as European influences among the Northwestern provinces of China. Furthermore, we identified a number of highly differentiated, putatively adaptive, loci (e.g., MTHFR, ADH7, and FADS, among others) that may be driven by immune response, climate, and diet in the Han Chinese. Finally, we have made available allele frequency estimates stratified by administrative divisions across China in the Geography of Genetic Variant browser for the broader community. By leveraging the largest currently available genetic data set for Han Chinese, we have gained insights into the history and population structure of the world's largest ethnic group.}, } @article {pmid30169786, year = {2018}, author = {Ng, CS and Li, WH}, title = {Genetic and Molecular Basis of Feather Diversity in Birds.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2572-2586}, pmid = {30169786}, issn = {1759-6653}, abstract = {Feather diversity is striking in many aspects. Although the development of feather has been studied for decades, genetic and genomic studies of feather diversity have begun only recently. Many questions remain to be answered by multidisciplinary approaches. In this review, we discuss three levels of feather diversity: Feather morphotypes, intraspecific variations, and interspecific variations. We summarize recent studies of feather evolution in terms of genetics, genomics, and developmental biology and provide perspectives for future research. Specifically, this review includes the following topics: 1) Diversity of feather morphotype; 2) feather diversity among different breeds of domesticated birds, including variations in pigmentation pattern, in feather length or regional identity, in feather orientation, in feather distribution, and in feather structure; and 3) diversity of feathers among avian species, including plumage color and morph differences between species and the regulatory differences in downy feather development between altricial and precocial birds. Finally, we discussed future research directions.}, } @article {pmid30169784, year = {2018}, author = {Kapopoulou, A and Pfeifer, SP and Jensen, JD and Laurent, S}, title = {The demographic history of African Drosophila melanogaster.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evy185}, pmid = {30169784}, issn = {1759-6653}, abstract = {As one of the most commonly utilized organisms in the study of local adaptation, an accurate characterization of the demographic history of Drosophila melanogaster remains as an important research question. This owes both to the inherent interest in characterizing the population history of this model organism, as well as to the well-established importance of an accurate null demographic model for increasing power and decreasing false positive rates in genomic scans for positive selection. While considerable attention has been afforded to this issue in non-African populations, less is known about the demographic history of African populations, including from the ancestral range of the species. While qualitative predictions and hypotheses have previously been forwarded, we here present a quantitative model fitting of the population history characterizing both the ancestral Zambian population range as well as the subsequently colonized west African populations, which themselves served as the source of multiple non-African colonization events. We here report the split time of the West African population at 72kya, a date corresponding to human migration into this region as well as a period of climatic changes in the African continent. Furthermore, we have estimated population sizes at this split time. These parameter estimates thus represent an important null model for future investigations in to African and non-African D. melanogaster populations alike.}, } @article {pmid30169718, year = {2018}, author = {Zhao, R and Takeuchi, T and Luo, YJ and Ishikawa, A and Kobayashi, T and Koyanagi, R and Villar-Briones, A and Yamada, L and Sawada, H and Iwanaga, S and Nagai, K and Satoh, N and Endo, K}, title = {Dual Gene Repertoires for Larval and Adult Shells Reveal Molecules Essential for Molluscan Shell Formation.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2751-2761}, pmid = {30169718}, issn = {1537-1719}, abstract = {Molluscan shells, mainly composed of calcium carbonate, also contain organic components such as proteins and polysaccharides. Shell organic matrices construct frameworks of shell structures and regulate crystallization processes during shell formation. To date, a number of shell matrix proteins (SMPs) have been identified, and their functions in shell formation have been studied. However, previous studies focused only on SMPs extracted from adult shells, secreted after metamorphosis. Using proteomic analyses combined with genomic and transcriptomic analyses, we have identified 31 SMPs from larval shells of the pearl oyster, Pinctada fucata, and 111 from the Pacific oyster, Crassostrea gigas. Larval SMPs are almost entirely different from those of adults in both species. RNA-seq data also confirm that gene expression profiles for larval and adult shell formation are nearly completely different. Therefore, bivalves have two repertoires of SMP genes to construct larval and adult shells. Despite considerable differences in larval and adult SMPs, some functional domains are shared by both SMP repertoires. Conserved domains include von Willebrand factor type A (VWA), chitin-binding (CB), carbonic anhydrase (CA), and acidic domains. These conserved domains are thought to play crucial roles in shell formation. Furthermore, a comprehensive survey of animal genomes revealed that the CA and VWA-CB domain-containing protein families expanded in molluscs after their separation from other Lophotrochozoan linages such as the Brachiopoda. After gene expansion, some family members were co-opted for molluscan SMPs that may have triggered to develop mineralized shells from ancestral, nonmineralized chitinous exoskeletons.}, } @article {pmid30169717, year = {2018}, author = {Arias, L and Schröder, R and Hübner, A and Barreto, G and Stoneking, M and Pakendorf, B}, title = {Cultural Innovations Influence Patterns of Genetic Diversity in Northwestern Amazonia.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2719-2735}, pmid = {30169717}, issn = {1537-1719}, abstract = {Human populations often exhibit contrasting patterns of genetic diversity in the mtDNA and the nonrecombining portion of the Y-chromosome (NRY), which reflect sex-specific cultural behaviors and population histories. Here, we sequenced 2.3 Mb of the NRY from 284 individuals representing more than 30 Native American groups from Northwestern Amazonia (NWA) and compared these data to previously generated mtDNA genomes from the same groups, to investigate the impact of cultural practices on genetic diversity and gain new insights about NWA population history. Relevant cultural practices in NWA include postmarital residential rules and linguistic exogamy, a marital practice in which men are required to marry women speaking a different language. We identified 2,969 SNPs in the NRY sequences, only 925 of which were previously described. The NRY and mtDNA data showed different sex-specific demographic histories: female effective population size has been larger than that of males through time, which might reflect larger variance in male reproductive success. Both markers show an increase in lineage diversification beginning ∼5,000 years ago, which may reflect the intensification of agriculture, technological innovations, and the expansion of regional trade networks documented in the archaeological evidence. Furthermore, we find similar excesses of NRY versus mtDNA between-population divergence at both the local and continental scale, suggesting long-term stability of female versus male migration. We also find evidence of the impact of sociocultural practices on diversity patterns. Finally, our study highlights the importance of analyzing high-resolution mtDNA and NRY sequences to reconstruct demographic history, since this can differ considerably between sexes.}, } @article {pmid30169705, year = {2018}, author = {Babonis, LS and DeBiasse, MB and Francis, WR and Christianson, LM and Moss, AG and Haddock, SHD and Martindale, MQ and Ryan, JF}, title = {Integrating Embryonic Development and Evolutionary History to Characterize Tentacle-Specific Cell Types in a Ctenophore.}, journal = {Molecular biology and evolution}, volume = {35}, number = {12}, pages = {2940-2956}, pmid = {30169705}, issn = {1537-1719}, abstract = {The origin of novel traits can promote expansion into new niches and drive speciation. Ctenophores (comb jellies) are unified by their possession of a novel cell type: the colloblast, an adhesive cell found only in the tentacles. Although colloblast-laden tentacles are fundamental for prey capture among ctenophores, some species have tentacles lacking colloblasts and others have lost their tentacles completely. We used transcriptomes from 36 ctenophore species to identify gene losses that occurred specifically in lineages lacking colloblasts and tentacles. We cross-referenced these colloblast- and tentacle-specific candidate genes with temporal RNA-Seq during embryogenesis in Mnemiopsis leidyi and found that both sets of candidates are preferentially expressed during tentacle morphogenesis. We also demonstrate significant upregulation of candidates from both data sets in the tentacle bulb of adults. Both sets of candidates were enriched for an N-terminal signal peptide and protein domains associated with secretion; among tentacle candidates we also identified orthologs of cnidarian toxin proteins, presenting tantalizing evidence that ctenophore tentacles may secrete toxins along with their adhesive. Finally, using cell lineage tracing, we demonstrate that colloblasts and neurons share a common progenitor, suggesting the evolution of colloblasts involved co-option of a neurosecretory gene regulatory network. Together these data offer an initial glimpse into the genetic architecture underlying ctenophore cell-type diversity.}, } @article {pmid30169693, year = {2018}, author = {Southworth, J and Armitage, P and Fallon, B and Dawson, H and Bryk, J and Carr, M}, title = {Patterns of Ancestral Animal Codon Usage Bias Revealed through Holozoan Protists.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2499-2511}, pmid = {30169693}, issn = {1537-1719}, abstract = {Choanoflagellates and filastereans are the closest known single celled relatives of Metazoa within Holozoa and provide insight into how animals evolved from their unicellular ancestors. Codon usage bias has been extensively studied in metazoans, with both natural selection and mutation pressure playing important roles in different species. The disparate nature of metazoan codon usage patterns prevents the reconstruction of ancestral traits. However, traits conserved across holozoan protists highlight characteristics in the unicellular ancestors of Metazoa. Presented here are the patterns of codon usage in the choanoflagellates Monosiga brevicollis and Salpingoeca rosetta, as well as the filasterean Capsaspora owczarzaki. Codon usage is shown to be remarkably conserved. Highly biased genes preferentially use GC-ending codons, however there is limited evidence this is driven by local mutation pressure. The analyses presented provide strong evidence that natural selection, for both translational accuracy and efficiency, dominates codon usage bias in holozoan protists. In particular, the signature of selection for translational accuracy can be detected even in the most weakly biased genes. Biased codon usage is shown to have coevolved with the tRNA species, with optimal codons showing complementary binding to the highest copy number tRNA genes. Furthermore, tRNA modification is shown to be a common feature for amino acids with higher levels of degeneracy and highly biased genes show a strong preference for using modified tRNAs in translation. The translationally optimal codons defined here will be of benefit to future transgenics work in holozoan protists, as their use should maximise protein yields from edited transgenes.}, } @article {pmid30169679, year = {2018}, author = {Palmer, AC and Chait, R and Kishony, R}, title = {Nonoptimal Gene Expression Creates Latent Potential for Antibiotic Resistance.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2669-2684}, pmid = {30169679}, issn = {1537-1719}, support = {R01 GM081617/GM/NIGMS NIH HHS/United States ; }, abstract = {Bacteria regulate genes to survive antibiotic stress, but regulation can be far from perfect. When regulation is not optimal, mutations that change gene expression can contribute to antibiotic resistance. It is not systematically understood to what extent natural gene regulation is or is not optimal for distinct antibiotics, and how changes in expression of specific genes quantitatively affect antibiotic resistance. Here we discover a simple quantitative relation between fitness, gene expression, and antibiotic potency, which rationalizes our observation that a multitude of genes and even innate antibiotic defense mechanisms have expression that is critically nonoptimal under antibiotic treatment. First, we developed a pooled-strain drug-diffusion assay and screened Escherichia coli overexpression and knockout libraries, finding that resistance to a range of 31 antibiotics could result from changing expression of a large and functionally diverse set of genes, in a primarily but not exclusively drug-specific manner. Second, by synthetically controlling the expression of single-drug and multidrug resistance genes, we observed that their fitness-expression functions changed dramatically under antibiotic treatment in accordance with a log-sensitivity relation. Thus, because many genes are nonoptimally expressed under antibiotic treatment, many regulatory mutations can contribute to resistance by altering expression and by activating latent defenses.}, } @article {pmid30169564, year = {2018}, author = {Yarwood, SA}, title = {The role of wetland microorganisms in plant-litter decomposition and soil organic matter formation: a critical review.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy175}, pmid = {30169564}, issn = {1574-6941}, abstract = {New soil organic matter (SOM) models highlight the role of microorganisms in plant litter decomposition and storage of microbial-derived carbon (C) molecules. Wetlands store more C per unit area than any other ecosystem, but SOM storage mechanisms such as aggregation and metal complexes are mostly untested in wetlands. This review discusses what is currently known about the role of microorganisms in SOM formation and C sequestrations, as well as, measures of microbial communities as they relate to wetland C cycling. Studies within the last decade have yielded new insights about microbial communities. For example, microbial communities appear to be adapted to short-term fluctuations in saturation and redox and researchers have observed synergistic pairings that in some cases run counter to thermodynamic theory. Significant knowledge gaps yet to be filled include: (i) What controls microbial access to and decomposition of plant litter and SOM? (ii) How does microbial community structure shape C fate, across different wetland types? (iii) What types of plant and microbial molecules contribute to SOM accumulation? Studies examining the active microbial community directly or that utilize multi-pronged approaches are shedding new light on microbial functional potential, however, and promise to improve wetland C models in the near future.}, } @article {pmid30169122, year = {2018}, author = {Krause, A and Seymour, H and Ramsay, M}, title = {Common and Founder Mutations for Monogenic Traits in Sub-Saharan African Populations.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {149-175}, doi = {10.1146/annurev-genom-083117-021256}, pmid = {30169122}, issn = {1545-293X}, abstract = {This review highlights molecular genetic studies of monogenic traits where common pathogenic mutations occur in black families from sub-Saharan Africa. Examples of founder mutations have been identified for oculocutaneous albinism, cystic fibrosis, Fanconi anemia, and Gaucher disease. Although there are few studies from Africa, some of the mutations traverse populations across the continent, and they are almost all different from the common mutations observed in non-African populations. Myotonic dystrophy is curiously absent among Africans, and nonsyndromic deafness does not arise from mutations in GJB2 and GJB7. Locus heterogeneity is present for Huntington disease, with two common triplet expansion loci in Africa, HTT and JPH3. These findings have important clinical consequences for diagnosis, treatment, and genetic counseling in affected families. We currently have just a glimpse of the molecular etiology of monogenic diseases in sub-Saharan Africa, a proverbial "ears of the hippo" situation.}, } @article {pmid30169121, year = {2018}, author = {Willis-Owen, SAG and Cookson, WOC and Moffatt, MF}, title = {The Genetics and Genomics of Asthma.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {223-246}, doi = {10.1146/annurev-genom-083117-021651}, pmid = {30169121}, issn = {1545-293X}, abstract = {Asthma is a common, clinically heterogeneous disease with strong evidence of heritability. Progress in defining the genetic underpinnings of asthma, however, has been slow and hampered by issues of inconsistency. Recent advances in the tools available for analysis-assaying transcription, sequence variation, and epigenetic marks on a genome-wide scale-have substantially altered this landscape. Applications of such approaches are consistent with heterogeneity at the level of causation and specify patterns of commonality with a wide range of alternative disease traits. Looking beyond the individual as the unit of study, advances in technology have also fostered comprehensive analysis of the human microbiome and its varied roles in health and disease. In this article, we consider the implications of these technological advances for our current understanding of the genetics and genomics of asthma.}, } @article {pmid30168795, year = {2018}, author = {Lachance, MA and Vale, HMM and Sperandio, EM and Carvalho, AOS and Santos, ARO and Grondin, C and Jacques, N and Casaregola, S and Rosa, CA}, title = {Wickerhamiella dianesei f.a., sp. nov. and Wickerhamiella kurtzmanii f.a., sp. nov., two yeast species isolated from plants and insects.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3351-3355}, doi = {10.1099/ijsem.0.003000}, pmid = {30168795}, issn = {1466-5034}, mesh = {Animals ; Asteraceae/microbiology ; Base Composition ; Bees/*microbiology ; Brazil ; Costa Rica ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Flowers/*microbiology ; French Guiana ; Ipomoea/microbiology ; Malpighiaceae/microbiology ; Mycological Typing Techniques ; *Phylogeny ; Plant Leaves/*microbiology ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {Six yeast strains representing two novel Wickerhamiella species were isolated from plants and insects collected in Costa Rica, Brazil, and French Guiana. They belong to a subclade containing Wickerhamiella domercqiae and Wickerhamiella bombiphila, and differ by approximately 12 % in the D1/D2 sequences of the large subunit rRNA gene from these species. The intergenic spacer (ITS) regions of the two novel species differ by around 19 and 27 %, respectively, from those of W. domercqiae. The novel species exhibit 5 % divergence in the D1/D2 sequences among them (around 4 % in the ITS). The names Wickerhamiella dianesei f.a., sp. nov. and Wickerhamiella kurtzmanii f.a., sp. nov. are proposed to accommodate these species, for which a sexual cycle has not been observed. Wickerhamiella dianesei was isolated from the stingless bee, Trigona fulviventris, collected in an Asteraceae flower in Costa Rica, and from leaves of Sabicea brasiliensis (Rubiaceae) and a flower of Byrsonima crassifolia (Malpighiaceae) in Brazil. Wickerhamiellsa kurtzmanii was isolated from a flower of Ipomoea batatoides (Convolvulaceae) in Costa Rica, the surface of a fruit of B. crassifolia in Brazil, and flowers in French Guiana. The type strains are Wickerhamiella dianesei UWOPS 00-107.1T (=CBS 14185=NRRL Y-63789; Mycobank number MB 827008) and Wickerhamiella kurtzmanii UWOPS 00-192.1T (=CBS 15383=NRRL Y-63979; MB 827011).}, } @article {pmid30168793, year = {2018}, author = {Li, Y and Li, Y and Wang, LW and Bao, J}, title = {Streptomyces dengpaensis sp. nov., an actinomycete isolated from desert soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3322-3326}, doi = {10.1099/ijsem.0.002994}, pmid = {30168793}, issn = {1466-5034}, mesh = {Actinobacteria/genetics ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; *Desert Climate ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; Tibet ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, designated strain XZHG99T, was isolated from soil taken from colour desert, Dengpa District, Tibet Autonomous Region, China. Its taxonomic position was determined by a polyphasic approach. The strain showed morphological and chemotaxonomic features typical of the genus Streptomyces: branched substrate and aerial mycelia, straight spore chains and smooth spores; ll-diaminopimelic acid in the cell-wall peptidoglycan; MK-9(H8), MK-9(H2), MK-9(H6) and MK-9(H10) as menaquinones; diphosphatidylglycerol, phospatidylethanolamine, phosphatidylinositol, phosphotidylinositol mannoside and phosphatidylglycerol as prominent phospholipids; iso-C16 : 0, anteiso-C15 : 0 and C16 : 0 as major cellular fatty acids; and DNA G+C content of 69.9 mol%. 16S rRNA gene sequence analysis indicated that strain XZHG99T showed high similarity to Streptomyces albiflavescensm20T (98.42 %) and Streptomyces krungchingensis KC-035T (98.14 %) as well as formed a monophyletic clade with them in the phylogenetic tree. Based on comparison of phenotypic properties and the low level of DNA-DNA relatedness, strain XZHG99T can be distinguished from phylogenetically related Streptomyces species and is suggested to represent a novel species of the genus Streptomyces, for which the name Streptomyces dengpaensis sp. nov. is proposed. The type strain is XZHG99T (=CGMCC 4.7472T=KCTC 49090T).}, } @article {pmid30168792, year = {2018}, author = {Thawai, C and He, YW and Tadtong, S}, title = {Jishengella zingiberis sp. nov., isolated from root tissue of Zingiber montanum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3345-3350}, doi = {10.1099/ijsem.0.002998}, pmid = {30168792}, issn = {1466-5034}, mesh = {Actinobacteria/genetics ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Micromonosporaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; Zingiberaceae/*microbiology ; }, abstract = {A novel actinomycete, strain PLAI 1-1T, which formed spiny single spore directly on substrate mycelium was isolated from root tissue of Zingiber montanum. The isolate contained meso-diaminopimelic acid and 3-hydroxydiaminopimelic acid in the cell-wall peptidoglycan. The acyl type of the cell-wall muramic acid was glycolyl. The whole-cell sugars of strain PLAI 1-1T were glucose, arabinose, xylose, ribose and a trace amount of mannose. The membrane phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine and phosphatidylinositol. The major menaquinone was MK-9 (H4). The main cellular fatty acids were iso-C15 : 0 and C17 : 1ω8c. The G+C content of the genomic DNA was 70.6 mol%. 16S rRNA gene sequence analysis revealed that strain PLAI 1-1T was a member of the genus Jishengella and had the highest 16S rRNA gene sequence similarity to Jishengella endophytica DSM 45430T (99.2 %). Based on the data of physiological and biochemical tests, including the result of DNA-DNA hybridization, strain PLAI 1-1T represents a novel species of the genus Jishengella, for which the name Jishengellazingiberis sp. nov. is proposed. The type strain is PLAI 1-1T (=TBRC 7644T=NBRC 113144T).}, } @article {pmid30168791, year = {2018}, author = {Liu, Q and Liu, HC and Zhou, YG and Xin, YH}, title = {Flavipsychrobacter stenotrophus gen. nov., sp. nov., a novel member of the phylum Bacteroidetes isolated from a glacier.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3340-3344}, doi = {10.1099/ijsem.0.002996}, pmid = {30168791}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Ice Cover/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tibet ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative strain, designated RB1R16T, was isolated from ice collected from the ice tongue surface of the Renlongba glacier in Tibet. Strain RB1R16T was catalase-negative, oxidase-negative and grew at 10-22 °C, pH 6.0-8.0 and in the presence of 0-0.5 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the strain RB1R16T belonged to Chitinophagaceae and formed an independent linkage. The highest level of 16S rRNA gene sequence similarities were found to Lacibacter cauensis CGMCC 1.7271T (90.3 %), Flavihumibacter cheonanensis WS16T (90.1 %) and Flavihumibacter solisilvae 3-3T (90.1 %). The major fatty acids were iso-C15 : 1 G, iso-C15 : 0, summed feature 4 (comprising iso-C17 : 1 I and/or anteiso-C17 : 1 B) and iso-C17 : 0 3OH. The polar lipids contained phosphatidylethanolamine, one unidentified aminolipid and four unidentified lipids. The quinone system contained menaquinone MK-7 as the only component. The DNA G+C content was 43.1 mol%. On the basis of a polyphasic approach, a novel species of a new genus Flavipsychrobacter stenotrophus gen. nov., sp. nov. within the family Chitinophagaceae is proposed, with RB1R16T (=CGMCC 1.16126T=NBRC 113112T) as the type strain.}, } @article {pmid30168790, year = {2018}, author = {Sujarit, K and Kudo, T and Ohkuma, M and Pathom-Aree, W and Lumyong, S}, title = {Streptomyces venetus sp. nov., an actinomycete with a blue aerial mycelium.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3333-3339}, doi = {10.1099/ijsem.0.002995}, pmid = {30168790}, issn = {1466-5034}, mesh = {Arecaceae/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Genes, Bacterial ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-positive bacterium, designated CMU-AB225T, was isolated from rhizosphere soil of an oil palm (Elaeis guineensis). The strain exhibited a blue aerial spore mass and a light cream to moderate yellow substrate mycelium and formed chains of spiny spores. Whole-cell hydrolysates consisted of ll-diaminopimelic acid, glucose, ribose, mannose and galactose. The predominant menaquinones were MK-9(H6), MK-9(H8) and MK-9(H4). The polar lipids profile contained diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol-mannoside, four unidentified lipids, two unidentified aminolipids and an unidentified glycolipid. The major cellular fatty acids (>10 %) were iso-C16 : 0, C16 : 0, anteiso-C15 : 0 and iso-C15 : 0. The G+C content of genomic DNA was 69.7 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CMU-AB225T was a member of the genus Streptomyces and formed a distinct phyletic line which was most closely related to Streptomyces koyangensis JCM 14915T, Streptomyces misionensis JCM 4497T and Streptomyces aurantiogriseus JCM 4346T. Multilocus sequence analysis (MLSA) using five housekeeping genes (atpD, gyrB, recA, rpoB and trpB) showed that the MLSA distances of strain CMU-AB225T to phylogenetically related species were greater than the 0.007 threshold. Moreover, the low values of DNA-DNA relatedness and phenotypic differences, especially a blue aerial mycelium, enabled strain CMU-AB225T to be distinguished from its closely related species. It is thus proposed that strain CMU-AB225T represents a novel species, namely Streptomyces venetus sp. nov. The type strain is CMU-AB225T (=JCM 31290T=TBRC 2001T).}, } @article {pmid30168666, year = {2018}, author = {Bornberg-Bauer, E and Harrison, MC and Jongepier, E}, title = {The first cockroach genome and its significance for understanding development and the evolution of insect eusociality.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {5}, pages = {251-253}, doi = {10.1002/jez.b.22826}, pmid = {30168666}, issn = {1552-5015}, } @article {pmid30168254, year = {2018}, author = {Lukas, P and Olsson, L}, title = {Bapx1 is required for jaw joint development in amphibians.}, journal = {Evolution & development}, volume = {20}, number = {6}, pages = {192-206}, doi = {10.1111/ede.12267}, pmid = {30168254}, issn = {1525-142X}, mesh = {Ambystoma mexicanum/genetics/growth & development ; Animals ; Anura/classification/genetics/*growth & development ; Branchial Region/cytology/metabolism ; Chondrocytes/metabolism ; Gene Knockdown Techniques ; Head/embryology ; Homeodomain Proteins/genetics/*metabolism ; Jaw/*embryology/metabolism ; Joints/*embryology/metabolism ; Transcription Factors/genetics/metabolism ; Xenopus Proteins/genetics/metabolism ; Xenopus laevis/genetics/growth & development ; }, abstract = {The acquisition of a movable jaw and a jaw joint are key events in gnathostome evolution. Jaws are derived from the neural crest derived pharyngeal skeleton and the transition from jawless to jawed vertebrates consists of major morphological changes, which must have a genetic foundation. Recent studies on the effects of bapx1 knockdown in fish and chicken indicate that bapx1 has acquired such a role in primary jaw joint development during vertebrate evolution, but evidence from amphibians is missing so far. In the present study, we use Ambystoma mexicanum, Bombina orientalis, and Xenopus laevis to investigate the effects of bapx1 knockdown on the development of these three different amphibians. Using morpholinos we downregulated the expression of bapx1 and obtain morphants with altered mandibular arch morphology. In the absence of bapx1 Meckeĺs cartilage and the palatoquadrate jaw joint initially develop separately but during further development the joint cavity between both fills with chondrocytes. This results in the fusion of both cartilages and the loss of the jaw joint. Despite this the jaw itself remains usable for feeding and breathing. We show that bapx1 plays a role in jaw joint maintenance during development and that the morphants morphology possibly mirrors the morphology of the jawless ancestors of the gnathostomes.}, } @article {pmid30167766, year = {2018}, author = {Akter, S and Huq, MA}, title = {Biological Synthesis of Ginsenoside Rd Using Paenibacillus horti sp. nov. Isolated from Vegetable Garden.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1566-1573}, pmid = {30167766}, issn = {1432-0991}, support = {NRF-2018R1C1B5041386//National Research Foundation of Korea/ ; }, mesh = {Bacterial Typing Techniques/methods ; Base Composition/genetics ; DNA, Bacterial/genetics ; Fatty Acids/genetics ; Gardens ; Ginsenosides/*biosynthesis/*genetics ; Nucleic Acid Hybridization/genetics ; Paenibacillus/*genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/methods ; Soil Microbiology ; Vegetables/*microbiology ; }, abstract = {A Gram-stain positive, aerobic, motile, rod-shaped, and ginsenoside Rd producing novel bacterial strain, designated as MAH-16T, was isolated from soil sample of a vegetable garden and was characterized by using a polyphasic approach. The colonies were beige color, smooth, circular, and 0.3-0.7 mm in diameter when grown on tryptone soya agar for 3 days. Strain MAH-16T can grow at 20-40 °C temperature, at pH 5.0-7.0 and at 0-1% NaCl. Cell growth occurs on nutrient agar, R2A agar, tryptone soya agar, and Luria-Bertani agar but not on MacConkey agar. The strain was positive for both catalase and oxidase test. The novel strain rapidly synthesized ginsenoside Rd from major ginsenoside Rb1. According to the 16S rRNA gene sequence comparisons, the isolate was identified as a member of the genus Paenibacillus and was most closely related to Paenibacillus barengoltzii SAFN-016T (97.1%), Paenibacillus faecis 656.84T (96.7%), and Paenibacillus konsidensis LBYT (96.2%). In DNA-DNA hybridization tests, the DNA relatedness between strain MAH-16T and its closest phylogenetic neighbor was below 45.0%. The genomic DNA G + C content of isolated strain was determined to be 52.0 mol% and the predominant isoprenoid quinine was menaquinone-7 (MK-7). The major fatty acids were identified as anteiso-C15:0. The genetic characteristics in combination with chemotaxonomic and physiological data demonstrated that strain MAH-16T represented a novel species within the genus Paenibacillus, for which the name Paenibacillus horti sp. nov. is proposed, with MAH-16T as the type strain (=KACC 19299T = CGMCC1.16487T).}, } @article {pmid30167104, year = {2018}, author = {Paynter, I and Genest, D and Saenz, E and Peri, F and Boucher, P and Li, Z and Strahler, A and Schaaf, C}, title = {Classifying ecosystems with metaproperties from terrestrial laser scanner data.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {2}, pages = {210-222}, doi = {10.1111/2041-210X.12854}, pmid = {30167104}, issn = {2041-210X}, abstract = {In this study, we introduce metaproperty analysis of terrestrial laser scanner (TLS) data, and demonstrate its application through several ecological classification problems. Metaproperty analysis considers pulse level and spatial metrics derived from the hundreds of thousands to millions of lidar pulses present in a single scan from a typical contemporary instrument. In such large aggregations, properties of the populations of lidar data reflect attributes of the underlying ecological conditions of the ecosystems.In this study, we provide the Metaproperty Classification Model to employ TLS metaproperty analysis for classification problems in ecology. We applied this to a proof-of-concept study, which classified 88 scans from rooms and forests with 100% accuracy, to serve as a template.We then applied the Metaproperty Classification Model in earnest, to separate scans from temperate and tropical forests with 97.09% accuracy (N = 224), and to classify scans from inland and coastal tropical rainforests with 84.07% accuracy (N = 270).The results demonstrate the potential for metaproperty analysis to identify subtle and important ecosystem conditions, including diseases and anthropogenic disturbances. Metaproperty analysis serves as an augmentation to contemporary object reconstruction applications of TLS in ecology, and can characterize regional heterogeneity.}, } @article {pmid30166629, year = {2018}, author = {de Barros Damgaard, P and Marchi, N and Rasmussen, S and Peyrot, M and Renaud, G and Korneliussen, T and Moreno-Mayar, JV and Pedersen, MW and Goldberg, A and Usmanova, E and Baimukhanov, N and Loman, V and Hedeager, L and Pedersen, AG and Nielsen, K and Afanasiev, G and Akmatov, K and Aldashev, A and Alpaslan, A and Baimbetov, G and Bazaliiskii, VI and Beisenov, A and Boldbaatar, B and Boldgiv, B and Dorzhu, C and Ellingvag, S and Erdenebaatar, D and Dajani, R and Dmitriev, E and Evdokimov, V and Frei, KM and Gromov, A and Goryachev, A and Hakonarson, H and Hegay, T and Khachatryan, Z and Khaskhanov, R and Kitov, E and Kolbina, A and Kubatbek, T and Kukushkin, A and Kukushkin, I and Lau, N and Margaryan, A and Merkyte, I and Mertz, IV and Mertz, VK and Mijiddorj, E and Moiyesev, V and Mukhtarova, G and Nurmukhanbetov, B and Orozbekova, Z and Panyushkina, I and Pieta, K and Smrčka, V and Shevnina, I and Logvin, A and Sjogren, KG and Štolcova, T and Taravella, AM and Tashbaeva, K and Tkachev, A and Tulegenov, T and Voyakin, D and Yepiskoposyan, L and Undrakhbold, S and Varfolomeev, V and Weber, A and Wilson Sayres, MA and Kradin, N and Allentoft, ME and Orlando, L and Nielsen, R and Sikora, M and Heyer, E and Kristiansen, K and Willerslev, E}, title = {Author Correction: 137 ancient human genomes from across the Eurasian steppes.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {E16}, doi = {10.1038/s41586-018-0488-1}, pmid = {30166629}, issn = {1476-4687}, abstract = {with In this Article, Angela M. Taravella and Melissa A. Wilson Sayres have been added to the author list (associated with: School of Life Sciences, Center for Evolution and Medicine, The Biodesign Institute, Arizona State University, Tempe, AZ, USA). The author list and Author Information section have been corrected online.}, } @article {pmid30166597, year = {2018}, author = {Culumber, ZW and Tobler, M}, title = {Publisher Correction: Sex-specific evolution during the diversification of live-bearing fishes.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1673}, doi = {10.1038/s41559-018-0672-6}, pmid = {30166597}, issn = {2397-334X}, abstract = {In the version of this Article originally published, some production notes starting "Should we change..." were mistakenly left in at the end of the section 'Sexual selection'; these notes have now been removed.}, } @article {pmid30166595, year = {2018}, author = {Du Toit, A}, title = {Maximizing delivery.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {582-583}, doi = {10.1038/s41579-018-0078-0}, pmid = {30166595}, issn = {1740-1534}, } @article {pmid30166493, year = {2018}, author = {Gouveia, SF}, title = {The detour that became a shortcut.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {942}, doi = {10.1126/science.361.6405.942}, pmid = {30166493}, issn = {1095-9203}, } @article {pmid30166492, year = {2018}, author = {Tan, L and Xing, D and Chang, CH and Li, H and Xie, XS}, title = {Three-dimensional genome structures of single diploid human cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {924-928}, doi = {10.1126/science.aat5641}, pmid = {30166492}, issn = {1095-9203}, support = {DP1 CA186693/CA/NCI NIH HHS/United States ; R01 HG010040/HG/NHGRI NIH HHS/United States ; }, mesh = {Algorithms ; Alleles ; Blood Cells/chemistry/ultrastructure ; Cell Line, Tumor ; Cell Nucleus/genetics/ultrastructure ; Chromatin/chemistry/genetics/*ultrastructure ; Chromosomes, Human, X/ultrastructure ; DNA/chemistry/*ultrastructure ; DNA Copy Number Variations ; *Diploidy ; Gene Expression Regulation ; *Genome, Human ; *Genomic Imprinting ; Haplotypes ; Humans ; Imaging, Three-Dimensional/methods ; Nucleic Acid Amplification Techniques ; *Nucleic Acid Conformation ; Protein Conformation ; Single-Cell Analysis/methods ; }, abstract = {Three-dimensional genome structures play a key role in gene regulation and cell functions. Characterization of genome structures necessitates single-cell measurements. This has been achieved for haploid cells but has remained a challenge for diploid cells. We developed a single-cell chromatin conformation capture method, termed Dip-C, that combines a transposon-based whole-genome amplification method to detect many chromatin contacts, called META (multiplex end-tagging amplification), and an algorithm to impute the two chromosome haplotypes linked by each contact. We reconstructed the genome structures of single diploid human cells from a lymphoblastoid cell line and from primary blood cells with high spatial resolution, locating specific single-nucleotide and copy number variations in the nucleus. The two alleles of imprinted loci and the two X chromosomes were structurally different. Cells of different types displayed statistically distinct genome structures. Such structural cell typing is crucial for understanding cell functions.}, } @article {pmid30166491, year = {2018}, author = {Nolan, C and Overpeck, JT and Allen, JRM and Anderson, PM and Betancourt, JL and Binney, HA and Brewer, S and Bush, MB and Chase, BM and Cheddadi, R and Djamali, M and Dodson, J and Edwards, ME and Gosling, WD and Haberle, S and Hotchkiss, SC and Huntley, B and Ivory, SJ and Kershaw, AP and Kim, SH and Latorre, C and Leydet, M and Lézine, AM and Liu, KB and Liu, Y and Lozhkin, AV and McGlone, MS and Marchant, RA and Momohara, A and Moreno, PI and Müller, S and Otto-Bliesner, BL and Shen, C and Stevenson, J and Takahara, H and Tarasov, PE and Tipton, J and Vincens, A and Weng, C and Xu, Q and Zheng, Z and Jackson, ST}, title = {Past and future global transformation of terrestrial ecosystems under climate change.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {920-923}, doi = {10.1126/science.aan5360}, pmid = {30166491}, issn = {1095-9203}, mesh = {*Biodiversity ; *Climate Change ; }, abstract = {Impacts of global climate change on terrestrial ecosystems are imperfectly constrained by ecosystem models and direct observations. Pervasive ecosystem transformations occurred in response to warming and associated climatic changes during the last glacial-to-interglacial transition, which was comparable in magnitude to warming projected for the next century under high-emission scenarios. We reviewed 594 published paleoecological records to examine compositional and structural changes in terrestrial vegetation since the last glacial period and to project the magnitudes of ecosystem transformations under alternative future emission scenarios. Our results indicate that terrestrial ecosystems are highly sensitive to temperature change and suggest that, without major reductions in greenhouse gas emissions to the atmosphere, terrestrial ecosystems worldwide are at risk of major transformation, with accompanying disruption of ecosystem services and impacts on biodiversity.}, } @article {pmid30166490, year = {2018}, author = {Deutsch, CA and Tewksbury, JJ and Tigchelaar, M and Battisti, DS and Merrill, SC and Huey, RB and Naylor, RL}, title = {Increase in crop losses to insect pests in a warming climate.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {916-919}, doi = {10.1126/science.aat3466}, pmid = {30166490}, issn = {1095-9203}, mesh = {Animals ; Basal Metabolism ; Climate ; Crops, Agricultural/*parasitology ; *Global Warming ; Insecta/*growth & development/metabolism ; Oryza/*parasitology ; Population ; Temperature ; Triticum/*parasitology ; Zea mays/*parasitology ; }, abstract = {Insect pests substantially reduce yields of three staple grains-rice, maize, and wheat-but models assessing the agricultural impacts of global warming rarely consider crop losses to insects. We use established relationships between temperature and the population growth and metabolic rates of insects to estimate how and where climate warming will augment losses of rice, maize, and wheat to insects. Global yield losses of these grains are projected to increase by 10 to 25% per degree of global mean surface warming. Crop losses will be most acute in areas where warming increases both population growth and metabolic rates of insects. These conditions are centered primarily in temperate regions, where most grain is produced.}, } @article {pmid30166489, year = {2018}, author = {Wu, X and Zhao, L and Jin, J and Pan, S and Li, W and Jin, X and Wang, G and Zhou, M and Frenking, G}, title = {Observation of alkaline earth complexes M(CO)8 (M = Ca, Sr, or Ba) that mimic transition metals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {912-916}, doi = {10.1126/science.aau0839}, pmid = {30166489}, issn = {1095-9203}, abstract = {The alkaline earth metals calcium (Ca), strontium (Sr), and barium (Ba) typically engage in chemical bonding as classical main-group elements through their ns and np valence orbitals, where n is the principal quantum number. Here we report the isolation and spectroscopic characterization of eight-coordinate carbonyl complexes M(CO)8 (where M = Ca, Sr, or Ba) in a low-temperature neon matrix. Analysis of the electronic structure of these cubic Oh -symmetric complexes reveals that the metal-carbon monoxide (CO) bonds arise mainly from [M(dπ)] → (CO)8 π backdonation, which explains the strong observed red shift of the C-O stretching frequencies. The corresponding radical cation complexes were also prepared in gas phase and characterized by mass-selected infrared photodissociation spectroscopy, confirming adherence to the 18-electron rule more conventionally associated with transition metal chemistry.}, } @article {pmid30166488, year = {2018}, author = {Qing, Y and Ionescu, SA and Pulcu, GS and Bayley, H}, title = {Directional control of a processive molecular hopper.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {908-912}, doi = {10.1126/science.aat3872}, pmid = {30166488}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Cysteine/chemistry ; DNA/chemistry ; Electricity ; Escherichia coli Proteins/chemistry ; Hemolysin Proteins/chemistry ; *Motion ; *Nanopores ; Sequence Analysis, DNA/*methods ; }, abstract = {Intrigued by the potential of nanoscale machines, scientists have long attempted to control molecular motion. We monitored the individual 0.7-nanometer steps of a single molecular hopper as it moved in an electric field along a track in a nanopore controlled by a chemical ratchet. The hopper demonstrated characteristics desired in a moving molecule: defined start and end points, processivity, no chemical fuel requirement, directional motion, and external control. The hopper was readily functionalized to carry cargos. For example, a DNA molecule could be ratcheted along the track in either direction, a prerequisite for nanopore sequencing.}, } @article {pmid30166487, year = {2018}, author = {Han, Q and Hsieh, YT and Meng, L and Wu, JL and Sun, P and Yao, EP and Chang, SY and Bae, SH and Kato, T and Bermudez, V and Yang, Y}, title = {High-performance perovskite/Cu(In,Ga)Se2 monolithic tandem solar cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {904-908}, doi = {10.1126/science.aat5055}, pmid = {30166487}, issn = {1095-9203}, abstract = {The combination of hybrid perovskite and Cu(In,Ga)Se2 (CIGS) has the potential for realizing high-efficiency thin-film tandem solar cells because of the complementary tunable bandgaps and excellent photovoltaic properties of these materials. In tandem solar device architectures, the interconnecting layer plays a critical role in determining the overall cell performance, requiring both an effective electrical connection and high optical transparency. We used nanoscale interface engineering of the CIGS surface and a heavily doped poly[bis(4-phenyl)(2,4,6-trimethylphenyl)amine] (PTAA) hole transport layer between the subcells that preserves open-circuit voltage and enhances both the fill factor and short-circuit current. A monolithic perovskite/CIGS tandem solar cell achieved a 22.43% efficiency, and unencapsulated devices under ambient conditions maintained 88% of their initial efficiency after 500 hours of aging under continuous 1-sun illumination.}, } @article {pmid30166486, year = {2018}, author = {Goebel, THW and Brodsky, EE}, title = {The spatial footprint of injection wells in a global compilation of induced earthquake sequences.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {899-904}, doi = {10.1126/science.aat5449}, pmid = {30166486}, issn = {1095-9203}, abstract = {Fluid injection can cause extensive earthquake activity, sometimes at unexpectedly large distances. Appropriately mitigating associated seismic hazards requires a better understanding of the zone of influence of injection. We analyze spatial seismicity decay in a global dataset of 18 induced cases with clear association between isolated wells and earthquakes. We distinguish two populations. The first is characterized by near-well seismicity density plateaus and abrupt decay, dominated by square-root space-time migration and pressure diffusion. Injection at these sites occurs within the crystalline basement. The second population exhibits larger spatial footprints and magnitudes, as well as a power law-like, steady spatial decay over more than 10 kilometers, potentially caused by poroelastic effects. Far-reaching spatial effects during injection may increase event magnitudes and seismic hazard beyond expectations based on purely pressure-driven seismicity.}, } @article {pmid30166485, year = {2018}, author = {Sigal, YM and Zhou, R and Zhuang, X}, title = {Visualizing and discovering cellular structures with super-resolution microscopy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {880-887}, doi = {10.1126/science.aau1044}, pmid = {30166485}, issn = {1095-9203}, support = {R35 GM122487/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cells/*ultrastructure ; Humans ; Imaging, Three-Dimensional/*methods ; Microscopy, Fluorescence/*methods ; Molecular Imaging/*methods ; Neurons/ultrastructure ; Synapses/ultrastructure ; }, abstract = {Super-resolution microscopy has overcome a long-held resolution barrier-the diffraction limit-in light microscopy and enabled visualization of previously invisible molecular details in biological systems. Since their conception, super-resolution imaging methods have continually evolved and can now be used to image cellular structures in three dimensions, multiple colors, and living systems with nanometer-scale resolution. These methods have been applied to answer questions involving the organization, interaction, stoichiometry, and dynamics of individual molecular building blocks and their integration into functional machineries in cells and tissues. In this Review, we provide an overview of super-resolution methods, their state-of-the-art capabilities, and their constantly expanding applications to biology, with a focus on the latter. We will also describe the current technical challenges and future advances anticipated in super-resolution imaging.}, } @article {pmid30166484, year = {2018}, author = {Cheng, Y}, title = {Single-particle cryo-EM-How did it get here and where will it go.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {876-880}, doi = {10.1126/science.aat4346}, pmid = {30166484}, issn = {1095-9203}, support = {R01 GM082893/GM/NIGMS NIH HHS/United States ; R01 GM098672/GM/NIGMS NIH HHS/United States ; R01 HL134183/HL/NHLBI NIH HHS/United States ; P50 GM082250/GM/NIGMS NIH HHS/United States ; P01 GM111126/GM/NIGMS NIH HHS/United States ; S10 OD020054/OD/NIH HHS/United States ; S10 OD021741/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Catalase/chemistry/ultrastructure ; Cryoelectron Microscopy/*methods/*trends ; Crystallography, X-Ray ; Humans ; Single Molecule Imaging/*methods/*trends ; Transient Receptor Potential Channels/chemistry ; }, abstract = {Cryo-electron microscopy, or simply cryo-EM, refers mainly to three very different yet closely related techniques: electron crystallography, single-particle cryo-EM, and electron cryotomography. In the past few years, single-particle cryo-EM in particular has triggered a revolution in structural biology and has become a newly dominant discipline. This Review examines the fascinating story of its start and evolution over the past 40-plus years, delves into how and why the recent technological advances have been so groundbreaking, and briefly considers where the technique may be headed in the future.}, } @article {pmid30166483, year = {2018}, author = {Farzadfard, F and Lu, TK}, title = {Emerging applications for DNA writers and molecular recorders.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {870-875}, doi = {10.1126/science.aat9249}, pmid = {30166483}, issn = {1095-9203}, support = {P50 GM098792/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins ; Biosensing Techniques ; Brain Mapping ; CRISPR-Associated Protein 9 ; Cell Engineering/methods ; DNA/chemistry/genetics ; Directed Molecular Evolution/methods ; Endonucleases ; Gene Editing/*trends ; Genetic Engineering/*trends ; Genome ; Humans ; Information Storage and Retrieval/*methods ; RNA, Guide/genetics ; Recombination, Genetic ; }, abstract = {Natural life is encoded by evolvable, DNA-based memory. Recent advances in dynamic genome-engineering technologies, which we collectively refer to as in vivo DNA writing, have opened new avenues for investigating and engineering biology. This Review surveys these technological advances, outlines their prospects and emerging applications, and discusses the features and current limitations of these technologies for building various genetic circuits for processing and recording information in living cells.}, } @article {pmid30166482, year = {2018}, author = {Knott, GJ and Doudna, JA}, title = {CRISPR-Cas guides the future of genetic engineering.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {866-869}, doi = {10.1126/science.aat5011}, pmid = {30166482}, issn = {1095-9203}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; CRISPR-Associated Protein 9 ; *CRISPR-Cas Systems ; DNA/analysis/chemistry/genetics ; Endonucleases/genetics/metabolism ; Gene Editing/*methods ; Genetic Engineering/*methods/*trends ; Humans ; Molecular Imaging ; Plants/genetics ; RNA/analysis/chemistry ; RNA, Guide/genetics ; Transcription, Genetic ; }, abstract = {The diversity, modularity, and efficacy of CRISPR-Cas systems are driving a biotechnological revolution. RNA-guided Cas enzymes have been adopted as tools to manipulate the genomes of cultured cells, animals, and plants, accelerating the pace of fundamental research and enabling clinical and agricultural breakthroughs. We describe the basic mechanisms that set the CRISPR-Cas toolkit apart from other programmable gene-editing technologies, highlighting the diverse and naturally evolved systems now functionalized as biotechnologies. We discuss the rapidly evolving landscape of CRISPR-Cas applications, from gene editing to transcriptional regulation, imaging, and diagnostics. Continuing functional dissection and an expanding landscape of applications position CRISPR-Cas tools at the cutting edge of nucleic acid manipulation that is rewriting biology.}, } @article {pmid30166481, year = {2018}, author = {Mao, S and Vinson, V}, title = {Power couple: Science and technology.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {864-865}, doi = {10.1126/science.361.6405.864}, pmid = {30166481}, issn = {1095-9203}, } @article {pmid30166480, year = {2018}, author = {Gomez-Uchida, D and Sepúlveda, M and Ernst, B and Contador, TA and Neira, S and Harrod, C}, title = {Chile's salmon escape demands action.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {857-858}, doi = {10.1126/science.aau7973}, pmid = {30166480}, issn = {1095-9203}, mesh = {Animals ; *Aquaculture ; Chile ; *Introduced Species ; *Salmon ; }, } @article {pmid30166479, year = {2018}, author = {Greytak, EM and Kaye, DH and Budowle, B and Moore, C and Armentrout, SL}, title = {Privacy and genetic genealogy data.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {857}, doi = {10.1126/science.aav0330}, pmid = {30166479}, issn = {1095-9203}, mesh = {*Genealogy and Heraldry ; Genetic Privacy ; Genetic Testing ; Pedigree ; *Privacy ; }, } @article {pmid30166478, year = {2018}, author = {Marshall, JC and Acuña, V and Allen, DC and Bonada, N and Boulton, AJ and Carlson, SM and Dahm, CN and Datry, T and Leigh, C and Negus, P and Richardson, JS and Sabater, S and Stevenson, RJ and Steward, AL and Stubbington, R and Tockner, K and Vander Vorste, R}, title = {Protecting U.S. temporary waterways.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {856-857}, doi = {10.1126/science.aav0839}, pmid = {30166478}, issn = {1095-9203}, mesh = {Biodiversity ; *Conservation of Water Resources ; *Rivers ; United States ; *United States Environmental Protection Agency ; }, } @article {pmid30166477, year = {2018}, author = {Masnadi, MS and El-Houjeiri, HM and Schunack, D and Li, Y and Englander, JG and Badahdah, A and Monfort, JC and Anderson, JE and Wallington, TJ and Bergerson, JA and Gordon, D and Koomey, J and Przesmitzki, S and Azevedo, IL and Bi, XT and Duffy, JE and Heath, GA and Keoleian, GA and McGlade, C and Meehan, DN and Yeh, S and You, F and Wang, M and Brandt, AR}, title = {Global carbon intensity of crude oil production.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {851-853}, doi = {10.1126/science.aar6859}, pmid = {30166477}, issn = {1095-9203}, } @article {pmid30166476, year = {2018}, author = {Armentrout, PB}, title = {18 electrons and counting.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {849-850}, doi = {10.1126/science.aau6622}, pmid = {30166476}, issn = {1095-9203}, mesh = {*Electrons ; *Scintillation Counting ; }, } @article {pmid30166475, year = {2018}, author = {Imielinski, M and Ladanyi, M}, title = {Fusion oncogenes-genetic musical chairs.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {848-849}, doi = {10.1126/science.aau8231}, pmid = {30166475}, issn = {1095-9203}, mesh = {*Oncogenes ; }, } @article {pmid30166474, year = {2018}, author = {Riegler, M}, title = {Insect threats to food security.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {846}, doi = {10.1126/science.aau7311}, pmid = {30166474}, issn = {1095-9203}, mesh = {Animals ; *Food Supply ; Insecta ; *Security Measures ; }, } @article {pmid30166473, year = {2018}, author = {Kolch, W and Kiel, C}, title = {From oncogenic mutation to dynamic code.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {844-845}, doi = {10.1126/science.aau8059}, pmid = {30166473}, issn = {1095-9203}, mesh = {*Genetic Code ; *Mutation ; }, } @article {pmid30166472, year = {2018}, author = {Holford, M and Daly, M and King, GF and Norton, RS}, title = {Venoms to the rescue.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {842-844}, doi = {10.1126/science.aau7761}, pmid = {30166472}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Humans ; *Venoms/chemistry/classification/pharmacology/therapeutic use ; }, } @article {pmid30166471, year = {2018}, author = {Kaiser, J}, title = {The Alzheimer's gamble.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {838-841}, doi = {10.1126/science.361.6405.838}, pmid = {30166471}, issn = {1095-9203}, mesh = {Alzheimer Disease/*drug therapy ; *Financing, Organized ; Humans ; National Institute on Aging (U.S.)/*economics ; United States ; }, } @article {pmid30166470, year = {2018}, author = {Servick, K}, title = {Social science studies get a 'generous' test.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {836}, doi = {10.1126/science.361.6405.836}, pmid = {30166470}, issn = {1095-9203}, mesh = {Humans ; *Intuition ; Literature ; Reading ; Reproducibility of Results ; *Social Sciences ; }, } @article {pmid30166469, year = {2018}, author = {Cohen, J}, title = {In dogs, CRISPR fixes a muscular dystrophy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {835}, doi = {10.1126/science.361.6405.835}, pmid = {30166469}, issn = {1095-9203}, mesh = {Animals ; *Clustered Regularly Interspaced Short Palindromic Repeats ; DNA Damage ; Dog Diseases/genetics/*therapy ; Dogs ; Dystrophin/*genetics ; *Gene Editing ; Genetic Therapy/*methods ; Humans ; Muscle, Skeletal/metabolism/pathology ; Muscular Dystrophy, Animal/genetics/*therapy ; Muscular Dystrophy, Duchenne/genetics/therapy ; Mutagenesis ; }, } @article {pmid30166468, year = {2018}, author = {Kaiser, J and Malakoff, D}, title = {Amid fears of idea theft, NIH targets foreign funding links.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {834}, doi = {10.1126/science.361.6405.834}, pmid = {30166468}, issn = {1095-9203}, mesh = {Biomedical Research/*economics ; Confidentiality ; *Financial Support ; Financing, Organized ; Humans ; *Intellectual Property ; National Institutes of Health (U.S.)/*economics ; Peer Review ; *Theft ; United States ; }, } @article {pmid30166467, year = {2018}, author = {Pennisi, E}, title = {Hybridization may give some parasites a leg up.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {832-833}, doi = {10.1126/science.361.6405.832}, pmid = {30166467}, issn = {1095-9203}, mesh = {Animals ; Chimera ; Feces/parasitology ; France/epidemiology ; Genomics ; *Host-Parasite Interactions ; Humans ; *Hybridization, Genetic ; Rivers/*parasitology ; Schistosoma/*genetics/pathogenicity ; Schistosomiasis/*epidemiology/*parasitology ; Snails/*parasitology ; }, } @article {pmid30166466, year = {2018}, author = {Service, RF}, title = {New pain drugs may lower overdose and addiction risk.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {831-832}, doi = {10.1126/science.361.6405.831}, pmid = {30166466}, issn = {1095-9203}, mesh = {*Analgesics, Opioid/chemistry/pharmacokinetics/pharmacology/therapeutic use ; Animals ; Blood-Brain Barrier/metabolism ; Congresses as Topic ; Dopamine/metabolism ; Drug Overdose/*prevention & control ; Humans ; *Morphinans/chemistry/pharmacokinetics/pharmacology/therapeutic use ; Oxycodone/*analogs & derivatives ; Receptors, Opioid, mu/*agonists ; Respiratory Insufficiency/chemically induced/prevention & control ; beta-Arrestin 2/agonists ; }, } @article {pmid30166465, year = {2018}, author = {Popkin, G}, title = {Can a transgenic chestnut restore a forest icon?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {830-831}, doi = {10.1126/science.361.6405.830}, pmid = {30166465}, issn = {1095-9203}, mesh = {Environmental Restoration and Remediation/*methods ; Fagaceae/*genetics ; *Forests ; Genes, Plant ; Genetic Engineering/*legislation & jurisprudence ; Plant Diseases/genetics/microbiology ; *Plants, Genetically Modified ; Pollination ; Trees/*genetics/microbiology ; Triticum/genetics ; United States ; United States Department of Agriculture ; }, } @article {pmid30166464, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {828-829}, doi = {10.1126/science.361.6405.828}, pmid = {30166464}, issn = {1095-9203}, } @article {pmid30166463, year = {2018}, author = {Berg, J}, title = {Revolutionary technologies.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {827}, doi = {10.1126/science.aav1775}, pmid = {30166463}, issn = {1095-9203}, mesh = {Crystallography, X-Ray/*trends ; *DNA, Recombinant ; Microscopy/*trends ; Polymerase Chain Reaction/*trends ; Sequence Analysis, DNA/*methods ; }, } @article {pmid30166462, year = {2018}, author = {Anderson, ND and de Borja, R and Young, MD and Fuligni, F and Rosic, A and Roberts, ND and Hajjar, S and Layeghifard, M and Novokmet, A and Kowalski, PE and Anaka, M and Davidson, S and Zarrei, M and Id Said, B and Schreiner, LC and Marchand, R and Sitter, J and Gokgoz, N and Brunga, L and Graham, GT and Fullam, A and Pillay, N and Toretsky, JA and Yoshida, A and Shibata, T and Metzler, M and Somers, GR and Scherer, SW and Flanagan, AM and Campbell, PJ and Schiffman, JD and Shago, M and Alexandrov, LB and Wunder, JS and Andrulis, IL and Malkin, D and Behjati, S and Shlien, A}, title = {Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {}, pmid = {30166462}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Adolescent ; Bone Neoplasms/*genetics/pathology ; Child ; DNA Replication ; Evolution, Molecular ; Female ; *Gene Rearrangement ; Genome, Human ; Humans ; Male ; Mutation ; Neoplasm Metastasis ; Neoplasm Recurrence, Local/genetics/pathology ; Oncogene Proteins, Fusion/*genetics ; Sarcoma, Ewing/*genetics ; Soft Tissue Neoplasms/*genetics/pathology ; }, abstract = {Sarcomas are cancers of the bone and soft tissue often defined by gene fusions. Ewing sarcoma involves fusions between EWSR1, a gene encoding an RNA binding protein, and E26 transformation-specific (ETS) transcription factors. We explored how and when EWSR1-ETS fusions arise by studying the whole genomes of Ewing sarcomas. In 52 of 124 (42%) of tumors, the fusion gene arises by a sudden burst of complex, loop-like rearrangements, a process called chromoplexy, rather than by simple reciprocal translocations. These loops always contained the disease-defining fusion at the center, but they disrupted multiple additional genes. The loops occurred preferentially in early replicating and transcriptionally active genomic regions. Similar loops forming canonical fusions were found in three other sarcoma types. Chromoplexy-generated fusions appear to be associated with an aggressive form of Ewing sarcoma. These loops arise early, giving rise to both primary and relapse Ewing sarcoma tumors, which can continue to evolve in parallel.}, } @article {pmid30166461, year = {2018}, author = {Fuertes, G and Banterle, N and Ruff, KM and Chowdhury, A and Pappu, RV and Svergun, DI and Lemke, EA}, title = {Comment on "Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {}, doi = {10.1126/science.aau8230}, pmid = {30166461}, issn = {1095-9203}, support = {R01 NS056114/NS/NINDS NIH HHS/United States ; }, mesh = {Hydrophobic and Hydrophilic Interactions ; Intrinsically Disordered Proteins ; Protein Conformation ; *Scattering, Small Angle ; Water ; *X-Ray Diffraction ; }, abstract = {Editors at Science requested our input on the above discussion (comment by Best et al and response by Riback et al) because both sets of authors use our data from Fuertes et al (2017) to support their arguments. The topic of discussion pertains to the discrepant inferences drawn from SAXS versus FRET measurements regarding the dimensions of intrinsically disordered proteins (IDPs) in aqueous solvents. Using SAXS measurements on labeled and unlabeled proteins, we ruled out the labels used for FRET measurements as the cause of discrepant inferences between the two methods. Instead, we propose that FRET and SAXS provide complementary readouts because of a decoupling of size and shape fluctuations that is intrinsic to finite-sized, heteropolymeric IDPs. Accounting for this decoupling resolves the discrepant inferences between the two methods, thus making a case for the utility of both methods.}, } @article {pmid30166460, year = {2018}, author = {Riback, JA and Bowman, MA and Zmyslowski, A and Knoverek, CR and Jumper, J and Kaye, EB and Freed, KF and Clark, PL and Sosnick, TR}, title = {Response to Comment on "Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {}, doi = {10.1126/science.aar7949}, pmid = {30166460}, issn = {1095-9203}, support = {R01 GM055694/GM/NIGMS NIH HHS/United States ; R01 GM097573/GM/NIGMS NIH HHS/United States ; P41 GM103622/GM/NIGMS NIH HHS/United States ; S10 OD018090/OD/NIH HHS/United States ; T32 EB009412/EB/NIBIB NIH HHS/United States ; T32 GM007183/GM/NIGMS NIH HHS/United States ; T32 GM008720/GM/NIGMS NIH HHS/United States ; }, mesh = {Hydrophobic and Hydrophilic Interactions ; Protein Conformation ; *Scattering, Small Angle ; Water ; *X-Ray Diffraction ; }, abstract = {Best et al claim that we provide no convincing basis to assert that a discrepancy remains between FRET and SAXS results on the dimensions of disordered proteins under physiological conditions. We maintain that a clear discrepancy is apparent in our and other recent publications, including results shown in the Best et al comment. A plausible origin is fluorophore interactions in FRET experiments.}, } @article {pmid30166459, year = {2018}, author = {Best, RB and Zheng, W and Borgia, A and Buholzer, K and Borgia, MB and Hofmann, H and Soranno, A and Nettels, D and Gast, K and Grishaev, A and Schuler, B}, title = {Comment on "Innovative scattering analysis shows that hydrophobic disordered proteins are expanded in water".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {}, doi = {10.1126/science.aar7101}, pmid = {30166459}, issn = {1095-9203}, support = {R01 NS056114/NS/NINDS NIH HHS/United States ; }, mesh = {Fluorescence Resonance Energy Transfer ; *Protein Conformation ; Protein Denaturation ; *Scattering, Small Angle ; Water ; X-Ray Diffraction ; }, abstract = {Riback et al (Reports, 13 October 2017, p. 238) used small-angle x-ray scattering (SAXS) experiments to infer a degree of compaction for unfolded proteins in water versus chemical denaturant that is highly consistent with the results from Förster resonance energy transfer (FRET) experiments. There is thus no "contradiction" between the two methods, nor evidence to support their claim that commonly used FRET fluorophores cause protein compaction.}, } @article {pmid30166458, year = {2018}, author = {Bugaj, LJ and Sabnis, AJ and Mitchell, A and Garbarino, JE and Toettcher, JE and Bivona, TG and Lim, WA}, title = {Cancer mutations and targeted drugs can disrupt dynamic signal encoding by the Ras-Erk pathway.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {}, doi = {10.1126/science.aao3048}, pmid = {30166458}, issn = {1095-9203}, support = {DP2 EB024247/EB/NIBIB NIH HHS/United States ; R01 CA169338/CA/NCI NIH HHS/United States ; R01 CA211052/CA/NCI NIH HHS/United States ; R01 CA204302/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; R01 GM055040/GM/NIGMS NIH HHS/United States ; DP2 CA174497/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; Extracellular Signal-Regulated MAP Kinases/*genetics ; Gene Expression Profiling ; Humans ; Lung Neoplasms/*drug therapy/*genetics ; Molecular Targeted Therapy ; Mutation ; Optogenetics ; Protein Conformation ; Protein Kinase Inhibitors/pharmacology/*therapeutic use ; Protein Multimerization/drug effects ; Proto-Oncogene Proteins B-raf/*antagonists & inhibitors/chemistry/*genetics ; Signal Transduction/*genetics ; }, abstract = {The Ras-Erk (extracellular signal-regulated kinase) pathway encodes information in its dynamics; the duration and frequency of Erk activity can specify distinct cell fates. To enable dynamic encoding, temporal information must be accurately transmitted from the plasma membrane to the nucleus. We used optogenetic profiling to show that both oncogenic B-Raf mutations and B-Raf inhibitors can cause corruption of this transmission, so that short pulses of input Ras activity are distorted into abnormally long Erk outputs. These changes can reshape downstream transcription and cell fates, resulting in improper decisions to proliferate. These findings illustrate how altered dynamic signal transmission properties, and not just constitutively increased signaling, can contribute to cell proliferation and perhaps cancer, and how optogenetic profiling can dissect mechanisms of signaling dysfunction in disease.}, } @article {pmid30166457, year = {2018}, author = {Nie, M and Zou, J and Xu, X and Liang, C and Fang, C and Li, B}, title = {Comment on "Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {}, doi = {10.1126/science.aau3016}, pmid = {30166457}, issn = {1095-9203}, mesh = {Biomass ; *Carbon Dioxide ; Climate ; *Poaceae ; }, abstract = {Reich et al (Reports, 20 April 2018, p. 317) reported that elevated carbon dioxide (eCO2) switched its effect from promoting C3 grasses to favoring C4 grasses in a long-term experiment. We argue that the authors did not appropriately elucidate the interannual climate variation as a potential mechanism for the reversal of C4-C3 biomass in response to eCO2.}, } @article {pmid30166452, year = {2018}, author = {Hinrichs, S and Scherschel, K and Krüger, S and Neumann, JT and Schwarzl, M and Yan, I and Warnke, S and Ojeda, FM and Zeller, T and Karakas, M and Keller, T and Meyer, C and Blankenberg, S and Westermann, D and Lindner, D}, title = {Precursor proadrenomedullin influences cardiomyocyte survival and local inflammation related to myocardial infarction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8727-E8736}, pmid = {30166452}, issn = {1091-6490}, mesh = {Adrenomedullin/*genetics/metabolism/pharmacology ; Aged ; Animals ; Apoptosis/drug effects/genetics ; Cells, Cultured ; Cytokines/metabolism ; Female ; Gene Expression/genetics ; Humans ; Inflammation/*genetics/metabolism ; Inflammation Mediators/metabolism ; Male ; Mice, Inbred C57BL ; Middle Aged ; Myocardial Infarction/*genetics/metabolism ; Myocytes, Cardiac/drug effects/*metabolism ; Protein Precursors/*genetics/metabolism/pharmacology ; }, abstract = {Increased adrenomedullin (ADM) levels are associated with various cardiac diseases such as myocardial infarction (MI). ADM is cleaved off from the full-length precursor protein proadrenomedullin (ProADM) during its posttranslational processing. To date, no biological effect of ProADM is reported, while ADM infusion leads to antiapoptotic effects and improved cardiac function. Using an MI mouse model, we found an induction of ProADM gene as well as protein expression during the early phase of MI. This was accompanied by apoptosis and increasing inflammation, which substantially influence the post-MI remodeling processes. Simulating ischemia in vitro, we demonstrate that ProADM expression was increased in cardiomyocytes and cardiac fibroblasts. Subsequently, we treated ischemic cardiomyocytes with either ProADM or ADM and found that both proteins increased survival. This effect was diminishable by blocking the ADM1 receptor. To investigate whether ProADM and ADM play a role in the regulation of cardiac inflammation, we analyzed chemokine expression after treatment of cells with both proteins. While ProADM induced an expression of proinflammatory cytokines, thus promoting inflammation, ADM reduced chemokine expression. On leukocytes, both proteins repressed chemokine expression, revealing antiinflammatory effects. However, ProADM but not ADM dampened concurrent activation of leukocytes. Our data show that the full-length precursor ProADM is biologically active by reducing apoptosis to a similar extent as ADM. We further assume that ProADM induces local inflammation in affected cardiac tissue but attenuates exaggerated inflammation, whereas ADM has low impact. Our data suggest that both proteins are beneficial during MI by influencing apoptosis and inflammation.}, } @article {pmid30166451, year = {2018}, author = {Li, Y and Gu, Q and Chen, C and Zhang, J and Liu, Q and Hu, X and Liu, J and Liu, Y and Ling, L and Tian, M and Wang, Y and Samarth, N and Li, S and Zhang, T and Feng, J and Wang, J}, title = {Nontrivial superconductivity in topological MoTe2-x S x crystals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9503-9508}, pmid = {30166451}, issn = {1091-6490}, abstract = {Topological Weyl semimetals (TWSs) with pairs of Weyl points and topologically protected Fermi arc states have broadened the classification of topological phases and provide superior platform for study of topological superconductivity. Here we report the nontrivial superconductivity and topological features of sulfur-doped Td -phase MoTe2 with enhanced Tc compared with type-II TWS MoTe2 It is found that Td -phase S-doped MoTe2 (MoTe2-x S x , x ∼ 0.2) is a two-band s-wave bulk superconductor (∼0.13 meV and 0.26 meV), where the superconducting behavior can be explained by the s+- pairing model. Further, measurements of the quasi-particle interference (QPI) patterns and a comparison with band-structure calculations reveal the existence of Fermi arcs in MoTe2-x S x More interestingly, a relatively large superconducting gap (∼1.7 meV) is detected by scanning tunneling spectroscopy on the sample surface, showing a hint of topological nontrivial superconductivity based on the pairing of Fermi arc surface states. Our work demonstrates that the Td -phase MoTe2-x S x is not only a promising topological superconductor candidate but also a unique material for study of s+- superconductivity.}, } @article {pmid30166450, year = {2018}, author = {Kneller, GR}, title = {Franck-Condon picture of incoherent neutron scattering.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9450-9455}, pmid = {30166450}, issn = {1091-6490}, abstract = {A spectroscopic interpretation of incoherent neutron scattering experiments is presented which is based on Franck-Condon-type probabilities for scattering-induced transitions between quantum states of the target. The resulting expressions for the scattering functions enable an energy landscape-oriented analysis of neutron scattering spectra as well as a physical interpretation of Van Hove's space-time correlation functions in the quantum regime that accounts for the scattering kinematics. They suggest moreover a combined analysis of quasielastic and elastic scattering that become inseparable for complex systems with slow power-law relaxation.}, } @article {pmid30166449, year = {2018}, author = {Jacquot, JP}, title = {Dark deactivation of chloroplast enzymes finally comes to light.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9334-9335}, pmid = {30166449}, issn = {1091-6490}, mesh = {*Chloroplasts ; *Darkness ; Light ; }, } @article {pmid30166448, year = {2018}, author = {Li, V and Michael, E and Balaguer, J and Herce Castañón, S and Summerfield, C}, title = {Gain control explains the effect of distraction in human perceptual, cognitive, and economic decision making.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8825-E8834}, pmid = {30166448}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 281628//European Research Council/International ; //Medical Research Council/United Kingdom ; 099741/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Attention/*physiology ; Brain Mapping/methods ; Cognition/*physiology ; Computer Simulation ; Decision Making/*physiology ; Feedback, Sensory/physiology ; Functional Neuroimaging/methods ; Gyrus Cinguli/*physiology ; Healthy Volunteers ; Humans ; *Models, Neurological ; Oxygen/blood ; }, abstract = {When making decisions, humans are often distracted by irrelevant information. Distraction has a different impact on perceptual, cognitive, and value-guided choices, giving rise to well-described behavioral phenomena such as the tilt illusion, conflict adaptation, or economic decoy effects. However, a single, unified model that can account for all these phenomena has yet to emerge. Here, we offer one such account, based on adaptive gain control, and additionally show that it successfully predicts a range of counterintuitive new behavioral phenomena on variants of a classic cognitive paradigm, the Eriksen flanker task. We also report that blood oxygen level-dependent signals in a dorsal network prominently including the anterior cingulate cortex index a gain-modulated decision variable predicted by the model. This work unifies the study of distraction across perceptual, cognitive, and economic domains.}, } @article {pmid30166447, year = {2018}, author = {Cubitt, TS and Montanaro, A and Piddock, S}, title = {Universal quantum Hamiltonians.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9497-9502}, pmid = {30166447}, issn = {1091-6490}, abstract = {Quantum many-body systems exhibit an extremely diverse range of phases and physical phenomena. However, we prove that the entire physics of any quantum many-body system can be replicated by certain simple, "universal" spin-lattice models. We first characterize precisely what it means for one quantum system to simulate the entire physics of another. We then fully classify the simulation power of all two-qubit interactions, thereby proving that certain simple models can simulate all others, and hence are universal. Our results put the practical field of analogue Hamiltonian simulation on a rigorous footing and take a step toward justifying why error correction may not be required for this application of quantum information technology.}, } @article {pmid30166441, year = {2018}, author = {Nishimasu, H and Shi, X and Ishiguro, S and Gao, L and Hirano, S and Okazaki, S and Noda, T and Abudayyeh, OO and Gootenberg, JS and Mori, H and Oura, S and Holmes, B and Tanaka, M and Seki, M and Hirano, H and Aburatani, H and Ishitani, R and Ikawa, M and Yachie, N and Zhang, F and Nureki, O}, title = {Engineered CRISPR-Cas9 nuclease with expanded targeting space.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1259-1262}, doi = {10.1126/science.aas9129}, pmid = {30166441}, issn = {1095-9203}, support = {P01 HD087157/HD/NICHD NIH HHS/United States ; DP1 MH100706/MH/NIMH NIH HHS/United States ; R01 DK097768/DK/NIDDK NIH HHS/United States ; R01 HD088412/HD/NICHD NIH HHS/United States ; R01 MH110049/MH/NIMH NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/*genetics ; CRISPR-Associated Protein 9 ; *CRISPR-Cas Systems ; Crystallography, X-Ray ; Endonucleases/*chemistry/*genetics ; *Gene Editing ; HEK293 Cells ; Humans ; Protein Engineering ; }, abstract = {The RNA-guided endonuclease Cas9 cleaves its target DNA and is a powerful genome-editing tool. However, the widely used Streptococcus pyogenes Cas9 enzyme (SpCas9) requires an NGG protospacer adjacent motif (PAM) for target recognition, thereby restricting the targetable genomic loci. Here, we report a rationally engineered SpCas9 variant (SpCas9-NG) that can recognize relaxed NG PAMs. The crystal structure revealed that the loss of the base-specific interaction with the third nucleobase is compensated by newly introduced non-base-specific interactions, thereby enabling the NG PAM recognition. We showed that SpCas9-NG induces indels at endogenous target sites bearing NG PAMs in human cells. Furthermore, we found that the fusion of SpCas9-NG and the activation-induced cytidine deaminase (AID) mediates the C-to-T conversion at target sites with NG PAMs in human cells.}, } @article {pmid30166440, year = {2018}, author = {Cao, J and Cusanovich, DA and Ramani, V and Aghamirzaie, D and Pliner, HA and Hill, AJ and Daza, RM and McFaline-Figueroa, JL and Packer, JS and Christiansen, L and Steemers, FJ and Adey, AC and Trapnell, C and Shendure, J}, title = {Joint profiling of chromatin accessibility and gene expression in thousands of single cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1380-1385}, doi = {10.1126/science.aau0730}, pmid = {30166440}, issn = {1095-9203}, support = {DP1 HG007811/HG/NHGRI NIH HHS/United States ; R01 HG006281/HG/NHGRI NIH HHS/United States ; DP2 HD088158/HD/NICHD NIH HHS/United States ; R35 GM124704/GM/NIGMS NIH HHS/United States ; T32 HL007828/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {A549 Cells ; Animals ; Chromatin/*metabolism ; Dexamethasone/pharmacology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation/drug effects ; Genomics/*methods ; HEK293 Cells ; Humans ; Kidney/cytology/drug effects ; Mice ; NIH 3T3 Cells ; Regulatory Elements, Transcriptional/drug effects ; Single-Cell Analysis/*methods ; Transcription, Genetic/drug effects ; }, abstract = {Although we can increasingly measure transcription, chromatin, methylation, and other aspects of molecular biology at single-cell resolution, most assays survey only one aspect of cellular biology. Here we describe sci-CAR, a combinatorial indexing-based coassay that jointly profiles chromatin accessibility and mRNA (CAR) in each of thousands of single cells. As a proof of concept, we apply sci-CAR to 4825 cells, including a time series of dexamethasone treatment, as well as to 11,296 cells from the adult mouse kidney. With the resulting data, we compare the pseudotemporal dynamics of chromatin accessibility and gene expression, reconstruct the chromatin accessibility profiles of cell types defined by RNA profiles, and link cis-regulatory sites to their target genes on the basis of the covariance of chromatin accessibility and transcription across large numbers of single cells.}, } @article {pmid30166439, year = {2018}, author = {Amoasii, L and Hildyard, JCW and Li, H and Sanchez-Ortiz, E and Mireault, A and Caballero, D and Harron, R and Stathopoulou, TR and Massey, C and Shelton, JM and Bassel-Duby, R and Piercy, RJ and Olson, EN}, title = {Gene editing restores dystrophin expression in a canine model of Duchenne muscular dystrophy.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {86-91}, pmid = {30166439}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; R01 AR067294/AR/NIAMS NIH HHS/United States ; R01 HL130253/HL/NHLBI NIH HHS/United States ; U54 HD087351/HD/NICHD NIH HHS/United States ; }, mesh = {Adenoviridae ; Animals ; CRISPR-Cas Systems ; Disease Models, Animal ; Dogs ; Dystrophin/*genetics/metabolism ; Female ; Gene Editing/*methods ; Gene Transfer Techniques ; Male ; Muscular Dystrophy, Duchenne/*therapy ; }, abstract = {Mutations in the gene encoding dystrophin, a protein that maintains muscle integrity and function, cause Duchenne muscular dystrophy (DMD). The deltaE50-MD dog model of DMD harbors a mutation corresponding to a mutational "hotspot" in the human DMD gene. We used adeno-associated viruses to deliver CRISPR gene editing components to four dogs and examined dystrophin protein expression 6 weeks after intramuscular delivery (n = 2) or 8 weeks after systemic delivery (n = 2). After systemic delivery in skeletal muscle, dystrophin was restored to levels ranging from 3 to 90% of normal, depending on muscle type. In cardiac muscle, dystrophin levels in the dog receiving the highest dose reached 92% of normal. The treated dogs also showed improved muscle histology. These large-animal data support the concept that, with further development, gene editing approaches may prove clinically useful for the treatment of DMD.}, } @article {pmid30166438, year = {2018}, author = {Xiang, Z and Kasahara, Y and Asaba, T and Lawson, B and Tinsman, C and Chen, L and Sugimoto, K and Kawaguchi, S and Sato, Y and Li, G and Yao, S and Chen, YL and Iga, F and Singleton, J and Matsuda, Y and Li, L}, title = {Quantum oscillations of electrical resistivity in an insulator.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {65-69}, doi = {10.1126/science.aap9607}, pmid = {30166438}, issn = {1095-9203}, abstract = {In metals, orbital motions of conduction electrons on the Fermi surface are quantized in magnetic fields, which is manifested by quantum oscillations in electrical resistivity. This Landau quantization is generally absent in insulators. Here, we report a notable exception in an insulator-ytterbium dodecaboride (YbB12). The resistivity of YbB12, which is of a much larger magnitude than the resistivity in metals, exhibits distinct quantum oscillations. These unconventional oscillations arise from the insulating bulk, even though the temperature dependence of the oscillation amplitude follows the conventional Fermi liquid theory of metals with a large effective mass. Quantum oscillations in the magnetic torque are also observed, albeit with a lighter effective mass.}, } @article {pmid30166437, year = {2018}, author = {Tsikou, D and Yan, Z and Holt, DB and Abel, NB and Reid, DE and Madsen, LH and Bhasin, H and Sexauer, M and Stougaard, J and Markmann, K}, title = {Systemic control of legume susceptibility to rhizobial infection by a mobile microRNA.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6411}, pages = {233-236}, doi = {10.1126/science.aat6907}, pmid = {30166437}, issn = {1095-9203}, mesh = {Gene Expression Regulation, Bacterial ; Lotus/*microbiology ; MicroRNAs/*genetics ; Plant Diseases/*microbiology/*prevention & control ; Rhizobium/genetics/*pathogenicity ; Root Nodules, Plant/*microbiology ; Symbiosis/genetics ; }, abstract = {Nitrogen-fixing root nodules on legumes result from two developmental processes, bacterial infection and nodule organogenesis. To balance symbiosis and plant growth, legume hosts restrict nodule numbers through an inducible autoregulatory process. Here, we present a mechanism where repression of a negative regulator ensures symbiotic susceptibility of uninfected roots of the host Lotus japonicus We show that microRNA miR2111 undergoes shoot-to-root translocation to control rhizobial infection through posttranscriptional regulation of the symbiosis suppressor TOO MUCH LOVE in roots. miR2111 maintains a susceptible default status in uninfected hosts and functions as an activator of symbiosis downstream of LOTUS HISTIDINE KINASE1-mediated cytokinin perception in roots and HYPERNODULATION ABERRANT ROOT FORMATION1, a shoot factor in autoregulation. The miR2111-TML node ensures activation of feedback regulation to balance infection and nodulation events.}, } @article {pmid30166436, year = {2018}, author = {Guo, L and Winzer, T and Yang, X and Li, Y and Ning, Z and He, Z and Teodor, R and Lu, Y and Bowser, TA and Graham, IA and Ye, K}, title = {The opium poppy genome and morphinan production.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {343-347}, doi = {10.1126/science.aat4096}, pmid = {30166436}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Benzylisoquinolines/*metabolism ; *Evolution, Molecular ; *Gene Duplication ; Gene Fusion ; Gene Order ; *Genome, Plant ; Morphinans/*metabolism ; Multigene Family ; NADPH-Ferrihemoprotein Reductase/genetics ; Papaver/*genetics/*metabolism ; Plant Proteins/genetics ; Synteny ; }, abstract = {Morphinan-based painkillers are derived from opium poppy (Papaver somniferum L.). We report a draft of the opium poppy genome, with 2.72 gigabases assembled into 11 chromosomes with contig N50 and scaffold N50 of 1.77 and 204 megabases, respectively. Synteny analysis suggests a whole-genome duplication at ~7.8 million years ago and ancient segmental or whole-genome duplication(s) that occurred before the Papaveraceae-Ranunculaceae divergence 110 million years ago. Syntenic blocks representative of phthalideisoquinoline and morphinan components of a benzylisoquinoline alkaloid cluster of 15 genes provide insight into how this cluster evolved. Paralog analysis identified P450 and oxidoreductase genes that combined to form the STORR gene fusion essential for morphinan biosynthesis in opium poppy. Thus, gene duplication, rearrangement, and fusion events have led to evolution of specialized metabolic products in opium poppy.}, } @article {pmid30166218, year = {2018}, author = {Smith, CM and Sassetti, CM}, title = {Modeling Diversity: Do Homogeneous Laboratory Strains Limit Discovery?.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {892-895}, doi = {10.1016/j.tim.2018.08.002}, pmid = {30166218}, issn = {1878-4380}, abstract = {The outcome of chronic infections is highly variable. The heterogeneous disease outcomes in natural populations differ from genetically homogeneous infection models. Here, we use tuberculosis as a 'case study' to contrast the genetic landscape in natural populations with standard infection models, discussing new strategies to bridge this gap.}, } @article {pmid30166071, year = {2018}, author = {Campbell, RF and McGrath, PT and Paaby, AB}, title = {Analysis of Epistasis in Natural Traits Using Model Organisms.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {11}, pages = {883-898}, doi = {10.1016/j.tig.2018.08.002}, pmid = {30166071}, issn = {0168-9525}, support = {R01 GM114170/GM/NIGMS NIH HHS/United States ; R35 GM119744/GM/NIGMS NIH HHS/United States ; }, abstract = {The ability to detect and understand epistasis in natural populations is important for understanding how biological traits are influenced by genetic variation. However, identification and characterization of epistasis in natural populations remains difficult due to statistical issues that arise as a result of multiple comparisons, and the fact that most genetic variants segregate at low allele frequencies. In this review, we discuss how model organisms may be used to manipulate genotypic combinations to power the detection of epistasis as well as test interactions between specific genes. Findings from a number of species indicate that statistical epistasis is pervasive between natural genetic variants. However, the properties of experimental systems that enable analysis of epistasis also constrain extrapolation of these results back into natural populations.}, } @article {pmid30166069, year = {2018}, author = {Yates, KL and Bouchet, PJ and Caley, MJ and Mengersen, K and Randin, CF and Parnell, S and Fielding, AH and Bamford, AJ and Ban, S and Barbosa, AM and Dormann, CF and Elith, J and Embling, CB and Ervin, GN and Fisher, R and Gould, S and Graf, RF and Gregr, EJ and Halpin, PN and Heikkinen, RK and Heinänen, S and Jones, AR and Krishnakumar, PK and Lauria, V and Lozano-Montes, H and Mannocci, L and Mellin, C and Mesgaran, MB and Moreno-Amat, E and Mormede, S and Novaczek, E and Oppel, S and Ortuño Crespo, G and Peterson, AT and Rapacciuolo, G and Roberts, JJ and Ross, RE and Scales, KL and Schoeman, D and Snelgrove, P and Sundblad, G and Thuiller, W and Torres, LG and Verbruggen, H and Wang, L and Wenger, S and Whittingham, MJ and Zharikov, Y and Zurell, D and Sequeira, AMM}, title = {Outstanding Challenges in the Transferability of Ecological Models.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {790-802}, doi = {10.1016/j.tree.2018.08.001}, pmid = {30166069}, issn = {1872-8383}, abstract = {Predictive models are central to many scientific disciplines and vital for informing management in a rapidly changing world. However, limited understanding of the accuracy and precision of models transferred to novel conditions (their 'transferability') undermines confidence in their predictions. Here, 50 experts identified priority knowledge gaps which, if filled, will most improve model transfers. These are summarized into six technical and six fundamental challenges, which underlie the combined need to intensify research on the determinants of ecological predictability, including species traits and data quality, and develop best practices for transferring models. Of high importance is the identification of a widely applicable set of transferability metrics, with appropriate tools to quantify the sources and impacts of prediction uncertainty under novel conditions.}, } @article {pmid30166000, year = {2018}, author = {Gore, AV and Rohner, N and Rétaux, S and Jeffery, WR}, title = {Seeing a bright future for a blind fish.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {207-208}, doi = {10.1016/j.ydbio.2018.08.004}, pmid = {30166000}, issn = {1095-564X}, mesh = {Animals ; Blindness/*genetics/*metabolism/*physiopathology ; Caves ; Characiformes/*genetics/*metabolism ; *Disease Models, Animal ; Mexico ; }, } @article {pmid30165899, year = {2018}, author = {Gupta, BP and Adhikari, A and Chaudhary, S}, title = {Hepatitis viruses in Kathmandu, Nepal: hospital-based study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {627}, pmid = {30165899}, issn = {1756-0500}, mesh = {Adult ; Female ; *Hepatitis/drug therapy/epidemiology/virology ; Hepatitis Antibodies ; Hepatitis E ; Hepatitis E virus ; Hepatitis Viruses ; Humans ; Male ; Nepal/epidemiology ; Prevalence ; }, abstract = {OBJECTIVE: The objective of this study was to see the aetiology and outcome of sporadic acute viral hepatitis (AVH) in Kathmandu, Nepal.

RESULTS: Among 210 patients, 94 (45%) were male and 116 (55%) were female. Mean age was 30 years. 52 (24.7%) out of 210 were positive for either of the hepatitis virus infection. Major causative agent for AVH among hepatitis positive patients were hepatitis E virus (HEV) in 36 (69.2%), followed by hepatitis A virus (HAV) 8 (15.3%), hepatitis B virus (HBV) 7 (13.4%) and hepatitis C virus (HCV) 1 (1.9%). The 158 (75.3%) patient were negative for all hepatitis viral markers. Co-infections with more than one virus were found in 4 (7.6%) patients. All liver-specific enzymes including bilirubin increased in hepatitis-infected patients. We found large number circulation of HEV in Kathmandu, Nepal, indicating that this region is endemic for hepatitis virus infection.}, } @article {pmid30165888, year = {2018}, author = {Lilja, M and Widerström, M and Lindh, J}, title = {Persisting post-infection symptoms 2 years after a large waterborne outbreak of Cryptosporidium hominis in northern Sweden.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {625}, pmid = {30165888}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Child ; Child, Preschool ; Cryptosporidiosis/*complications/epidemiology ; Cryptosporidium ; Diarrhea/*etiology ; Disease Outbreaks ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Sweden ; Young Adult ; }, abstract = {OBJECTIVES: In 2010-2011, a large waterborne outbreak of Cryptosporidium hominis affected the city of Östersund in Sweden. Previous findings had suggested that gastrointestinal symptoms can persist for up to 11 months after the initial infection. Here we investigated whether the parasite could cause sequelae in infected individuals up to 28 months after the outbreak. We compared cases linked to the outbreak and the previous follow-up study with non-cases regarding symptoms present up to 28 months after the initial infection. We investigated whether cases were more likely to report a list of symptoms at follow-up compared to non-cases, calculating odds ratio and 95% confidence interval obtained through logistic regression.

RESULTS: A total of 559 individuals (215 cases) were included in the study. Forty-eight percent of the outbreak cases reported symptoms at follow-up. Compared to non-cases, cases were more likely to report watery diarrhea, diarrhea, abdominal pain, fatigue, nausea, headache, or joint stiffness/pain/discomfort at follow-up after adjusting for age and sex. Our findings suggest that gastrointestinal symptoms and joint pain can persist several years after the initial Cryptosporidium infection and should be regarded as a potential cause of unexplained gastrointestinal symptoms or joint pain in people who have had this infection.}, } @article {pmid30165886, year = {2018}, author = {Bobo, FT and Thanasekaran, P and Joice, AJR and Yadecha, B and Alebel, A}, title = {Susceptibility to cigarette smoking and associated factors among high school students in western Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {626}, pmid = {30165886}, issn = {1756-0500}, mesh = {Adolescent ; *Cigarette Smoking ; Cross-Sectional Studies ; Ethiopia ; Female ; Humans ; Male ; Prevalence ; Smoking ; *Students ; Surveys and Questionnaires ; *Tobacco Smoke Pollution ; }, abstract = {OBJECTIVE: Tobacco smoking is one of the leading causes of preventable premature death worldwide. Adolescence is a common period at which most of the established smokers start experimenting and smoking. The aim of the study was to determine the prevalence of susceptibility to cigarette smoking and associated factors among high school students in western Ethiopia.

RESULT: The prevalence of susceptibility to cigarette smoking among the study participants was 16.9%. Two-third (65.9%, 95% CI; 62.77, 68.87) of the students reported that they are exposed to second hand smoking in public areas. Students, whose father smoked (OR 2.76, 95% CI [1.26, 6.09]), whose friends smoked (OR 3.73 95% CI [1.57, 8.90]). Adolescents who have the perception that boys who smoke are attractive (OR 2.26, 95% CI [1.24, 4.09]) and smoking cigarettes makes young people look cool (OR 1.47, 95% CI; [1.01, 2.17]) were more likely to be susceptible to smoking. Having the knowledge that tobacco smoking is harmful (OR .43, CI 95% [.28, .67]) to health was found to be a protective factor against susceptibility to smoking cigarette.}, } @article {pmid30165832, year = {2018}, author = {Sørensen, MV and Graae, BJ and Hagen, D and Enquist, BJ and Nystuen, KO and Strimbeck, R}, title = {Experimental herbivore exclusion, shrub introduction, and carbon sequestration in alpine plant communities.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {29}, pmid = {30165832}, issn = {1472-6785}, support = {23060/E10//Norges Forskningsråd/International ; }, abstract = {BACKGROUND: Shrub cover in arctic and alpine ecosystems has increased in recent decades, and is predicted to further increase with climate change. Changes in shrub abundance may alter ecosystem carbon (C) sequestration and storage, with potential positive feedback on global C cycling. Small and large herbivores may reduce shrub expansion and thereby counteract the positive feedback on C cycling, but herbivore pressures have also changed in the alpine-arctic tundra; the increased shrub cover together with changes in herbivore pressure is leading to unpredictable changes in carbon sequestration and storage. In this study we investigate the importance of herbivory and shrub introduction for carbon sequestration in the short term. We measured standing biomass and daytime mid-growing season carbon fluxes in plots in a full factorial design where we excluded small and large mammalian herbivores and introduced Salix by planting Salix transplants. We used three study sites: one Empetrum-dominated heath, one herb- and cryptogam-dominated meadow, and one Salix-dominated shrub community in the low-alpine zone of the Dovre Mountains, Central Norway.

RESULTS: After 2 years, significant treatment effects were recorded in the heath community, but not in the meadow and shrub communities. In the heath community cessation of herbivory increased standing biomass due to increased biomass of dwarf shrubs. Cessation of herbivory also reduced biomass of bryophytes and ecosystem respiration (ER). Except for an increase in biomass of deciduous shrubs caused by the Salix introduction, the only effect of Salix introduction was an increase in biomass of graminoids in the heath.

CONCLUSIONS: Our short-term study demonstrated that herbivore exclusion had small but still significant effects on heath vegetation, whereas such effects were not apparent in the herb-and cryptogam-dominated meadow and the Salix-dominated shrub community. Following the treatments over more years is needed to estimate the long-term effects on community structure and the consequences for C sequestration in the three plant communities. Such data are important for predicting the impact of shrub expansion on C budgets from alpine regions.}, } @article {pmid30165827, year = {2018}, author = {Aguilar, A and Mora, Y and Dávalos, A and Girard, L and Mora, J and Peralta, H}, title = {Analysis of genome sequence and symbiotic ability of rhizobial strains isolated from seeds of common bean (Phaseolus vulgaris).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {645}, pmid = {30165827}, issn = {1471-2164}, support = {IN208216//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; 213606//Consejo Nacional de Ciencia y Tecnología/ ; }, mesh = {DNA, Bacterial ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Phaseolus/*microbiology ; Rhizobium/classification/genetics/*physiology ; Root Nodules, Plant/*genetics/growth & development ; Seeds/*genetics/growth & development ; Sequence Analysis, DNA ; *Symbiosis ; }, abstract = {BACKGROUND: Rhizobia are alpha-proteobacteria commonly found in soil and root nodules of legumes. It was recently reported that nitrogen-fixing rhizobia also inhabit legume seeds. In this study, we examined whole-genome sequences of seven strains of rhizobia isolated from seeds of common bean (Phaseolus vulgaris).

RESULTS: Rhizobial strains included in this study belonged to three different species, including Rhizobium phaseoli, R. leguminosarum, and R. grahamii. Genome sequence analyses revealed that six of the strains formed three pairs of highly related strains. Both strains comprising a pair shared all but one plasmid. In two out of three pairs, one of the member strains was effective in nodulation and nitrogen fixation, whereas the other was ineffective. The genome of the ineffective strain in each pair lacked several genes responsible for symbiosis, including nod, nif, and fix genes, whereas that of the effective strain harbored the corresponding genes in clusters, suggesting that recombination events provoked gene loss in ineffective strains. Comparisons of genomic sequences between seed strains and nodule strains of the same species showed high conservation of chromosomal sequences and lower conservation of plasmid sequences. Approximately 70% of all genes were shared among the strains of each species. However, paralogs were more abundant in seed strains than in nodule strains. Functional analysis showed that seed strains were particularly enriched in genes involved in the transport and metabolism of amino acids and carbohydrates, biosynthesis of cofactors and in transposons and prophages. Genomes of seed strains harbored several intact prophages, one of which was inserted at exactly the same genomic position in three strains of R. phaseoli and R. leguminosarum. The R. grahamii strain carried a prophage similar to a gene transfer agent (GTA); this represents the first GTA reported for this genus.

CONCLUSIONS: Seeds represent a niche for bacteria; their access by rhizobia possibly triggered the infection of phages, recombination, loss or gain of plasmids, and loss of symbiosis genes. This process probably represents ongoing evolution that will eventually convert these strains into obligate endophytes.}, } @article {pmid30165824, year = {2018}, author = {Gabay, G and Dahan, Y and Izhaki, Y and Faigenboim, A and Ben-Ari, G and Elkind, Y and Flaishman, MA}, title = {High-resolution genetic linkage map of European pear (Pyrus communis) and QTL fine-mapping of vegetative budbreak time.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {175}, pmid = {30165824}, issn = {1471-2229}, mesh = {Chromosome Mapping ; Chromosomes, Plant/*genetics ; *Genetic Linkage ; Phenotype ; Polymorphism, Single Nucleotide ; Pyrus/*genetics/growth & development ; Quantitative Trait Loci/*genetics ; }, abstract = {BACKGROUND: Genomic analysis technologies can promote efficient fruit tree breeding. Genotyping by sequencing (GBS) enables generating efficient data for high-quality genetic map construction and QTL analysis in a relatively accessible way. Furthermore, High-resolution genetic map construction and accurate QTL detection can significantly narrow down the putative candidate genes associated with important plant traits.

RESULTS: We genotyped 162 offspring in the F1 'Spadona' x 'Harrow Sweet' pear population using GBS. An additional 21 pear accessions, including the F1 population's parents, from our germplasm collection were subjected to GBS to examine diverse genetic backgrounds that are associated to agriculturally relevant traits and to enhance the power of SNP calling. A standard SNP calling pipeline identified 206,971 SNPs with Asian pear ('Suli') as the reference genome and 148,622 SNPs with the European genome ('Bartlett'). These results enabled constructing a genetic map, after further stringent SNP filtering, consisting of 2036 markers on 17 linkage groups with a length of 1433 cM and an average marker interval of 0.7 cM. We aligned 1030 scaffolds covering a total size of 165.5 Mbp (29%) of the European pear genome to the 17 linkage groups. For high-resolution QTL analysis covering the whole genome, we used phenotyping for vegetative budbreak time in the F1 population. New QTLs associated to vegetative budbreak time were detected on linkage groups 5, 13 and 15. A major QTL on linkage group 8 and an additional QTL on linkage group 9 were confirmed. Due to the significant genotype-by-environment (GxE) effect, we were able to identify novel interaction QTLs on linkage groups 5, 8, 9 and 17. Phenotype-genotype association analysis in the pear accessions for main genotype effect was conducted to support the QTLs detected in the F1 population. Significant markers were detected on every linkage group to which main genotype effect QTLs were mapped.

CONCLUSIONS: This is the first vegetative budbreak study of European pear that makes use of high-resolution genetic mapping. These results provide tools for marker-assisted selection and accurate QTL analysis in pear, and specifically at vegetative budbreak, considering the significant GxE and phenotype-plasticity effects.}, } @article {pmid30165820, year = {2018}, author = {Adetoye, A and Pinloche, E and Adeniyi, BA and Ayeni, FA}, title = {Characterization and anti-salmonella activities of lactic acid bacteria isolated from cattle faeces.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {96}, pmid = {30165820}, issn = {1471-2180}, abstract = {BACKGROUND: Non typhoidal salmonellosis is one of the neglected zoonoses in most African countries. The use of sub-therapeutic doses of antibiotics as animal growth promoter enhances the emergence and dissemination of antimicrobial resistance in bacteria with food animal reservoirs and may also results in antibiotics residue in animal products. One promising alternative to antibiotics in animal feed is Lactic Acid Bacteria (LAB) as probiotics. This study was carried out to determine the anti-salmonella activities and suitability of LAB isolated from cattle faeces in Nigeria as potential probiotics in cattle feed.

METHOD: The test Salmonella enterica spp strains and LAB were isolated from cattle faeces and identified by MALDI-TOF MS and partial sequencing of 16S rRNA genes respectively. The anti-salmonella activities of the isolated LAB in co-culture, cell-free supernatant, inhibition of growth by viable LAB cells and quantification of organic acids were determined by standard techniques. The ability of the LAB strains to withstand gastric conditions, antibiotic susceptibility and their haemolytic ability on blood agar were also determined.

RESULTS: A total of 88 LAB belonging to 15 species were isolated and identified from cattle faeces. The most abundant species were Streptococcus infantarius (26), Enterococcus hirae (12), Lactobacillus amylovorus (10), Lactobacillus mucosae (10) and Lactobacillus ingluviei (9). Most of the LAB strains showed good anti-salmonella activities against the test Salmonella enterica spp. with 2 Lactobacillus strains; Lactobacillus amylovorus C94 and Lactobacillus salivarius C86 exhibiting remarkable anti-salmonella activities with total inhibition of Salmonella spp after 18 hours of co-incubation. The selected strains were able to survive simultaneous growth at pH 3 and 7% bile concentration and are non hemolytic.

CONCLUSION: This study reports the vast diversity of culturable LAB in cattle faeces from Nigeria and their putative in-vitro antibacterial activity against Salmonella enterica spp isolated from cattle. Lactobacillus amylovorus C94 and Lactobacillus salivarius C86 demonstrated promising probiotic potentials in-vitro and will be further tested in-vivo in animal field trial.}, } @article {pmid30165819, year = {2018}, author = {Adamczyk-Popławska, M and Bandyra, K and Kwiatek, A}, title = {Activity of Vsr endonucleases encoded by Neisseria gonorrhoeae FA1090 is influenced by MutL and MutS proteins.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {95}, pmid = {30165819}, issn = {1471-2180}, abstract = {BACKGROUND: The functioning of DNA repair systems is based on correct interactions between proteins involved in DNA repair. Very Short Patch (VSP) repair is a DNA repair system that corrects mismatches resulting from the deamination of 5-methylcytosine. The key enzyme in the VSP system is Vsr endonuclease, which can cleave mismatched DNA independently of accessory proteins. Until now, in vivo activity has only been shown for V.EcoKDcm - the only Vsr endonuclease in Escherichia coli. Additionally, the VSP system of E. coli is the only one for which interactions between proteins of the system have been demonstrated. Neisseria gonorrhoeae FA1090 is the first bacterium that we previously demonstrated to encode two active in vitro Vsr endonucleases: V.NgoAXIII and V.NgoAXIV.

RESULTS: We elucidate the mutator phenotype of N. gonorrhoeae mutants with disrupted genes encoding V.NgoAXIII or V.NgoAXIV endonuclease. Furthermore, we investigate the interactions between gonococcal Vsr endonucleases and MutL and MutS proteins. The Vsr endonucleases physically interact with gonococcal MutL protein but not with MutS protein. In the presence of the MutL protein, the efficiency of DNA cleavage by both V.NgoAXIII and V.NgoAXIV endonucleases increases, resulting in a decrease in the amount of Vsr enzyme required to complete digestion of mismatched DNA. Both Vsr endonucleases are also stimulated in vitro by the MutL protein of E. coli. In turn, the gonococcal MutS protein hinders DNA cleavage by the Vsr endonucleases. However, this effect is overridden in the presence of MutL, and furthermore, the simultaneous presence of MutL and MutS causes an increase in the efficiency of DNA cleavage by the Vsr endonucleases compared to the reaction catalyzed by V.NgoAXIII or V.NgoAXIV alone.

CONCLUSIONS: For the first time, interactions between proteins of the DNA repair system encoded by N. gonorrhoeae that are responsible for the correction of mismatches resulting from the 5-methylcytosine deamination were identified. The increase in activity of Vsr endonucleases in the presence of MutL protein could allow for reduced synthesis of the Vsr endonucleases in cells, and the susceptibility of gonococcal Vsr endonucleases on MutL protein of E. coli implies a universal mechanism of Vsr stimulation by MutL protein.}, } @article {pmid30165817, year = {2018}, author = {Enault, S and Muñoz, D and Simion, P and Ventéo, S and Sire, JY and Marcellini, S and Debiais-Thibaud, M}, title = {Evolution of dental tissue mineralization: an analysis of the jawed vertebrate SPARC and SPARC-L families.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {127}, pmid = {30165817}, issn = {1471-2148}, support = {1151196//FONDECYT REGULAR/International ; 12-BSV7-0020//Agence Nationale de la Recherche/International ; PEPS ExoMod//Centre National de la Recherche Scientifique/International ; }, mesh = {Animals ; *Biological Evolution ; Collagen Type I/genetics/metabolism ; Collagen Type II/genetics/metabolism ; Dental Enamel/metabolism ; Gene Expression Regulation, Developmental ; Jaw/*anatomy & histology ; Minerals/*metabolism ; Osteonectin/genetics/*metabolism ; Phylogeny ; Tooth/embryology/*metabolism ; Vertebrates/*anatomy & histology/genetics ; }, abstract = {BACKGROUND: The molecular bases explaining the diversity of dental tissue mineralization across gnathostomes are still poorly understood. Odontodes, such as teeth and body denticles, are serial structures that develop through deployment of a gene regulatory network shared between all gnathostomes. Dentin, the inner odontode mineralized tissue, is produced by odontoblasts and appears well-conserved through evolution. In contrast, the odontode hypermineralized external layer (enamel or enameloid) produced by ameloblasts of epithelial origin, shows extensive structural variations. As EMP (Enamel Matrix Protein) genes are as yet only found in osteichthyans where they play a major role in the mineralization of teeth and others skeletal organs, our understanding of the molecular mechanisms leading to the mineralized odontode matrices in chondrichthyans remains virtually unknown.

RESULTS: We undertook a phylogenetic analysis of the SPARC/SPARC-L gene family, from which the EMPs are supposed to have arisen, and examined the expression patterns of its members and of major fibrillar collagens in the spotted catshark Scyliorhinus canicula, the thornback ray Raja clavata, and the clawed frog Xenopus tropicalis. Our phylogenetic analyses reveal that the single chondrichthyan SPARC-L gene is co-orthologous to the osteichthyan SPARC-L1 and SPARC-L2 paralogues. In all three species, odontoblasts co-express SPARC and collagens. In contrast, ameloblasts do not strongly express collagen genes but exhibit strikingly similar SPARC-L and EMP expression patterns at their maturation stage, in the examined chondrichthyan and osteichthyan species, respectively.

CONCLUSIONS: A well-conserved odontoblastic collagen/SPARC module across gnathostomes further confirms dentin homology. Members of the SPARC-L clade evolved faster than their SPARC paralogues, both in terms of protein sequence and gene duplication. We uncover an osteichthyan-specific duplication that produced SPARC-L1 (subsequently lost in pipidae frogs) and SPARC-L2 (independently lost in teleosts and tetrapods).Our results suggest the ameloblastic expression of the single chondrichthyan SPARC-L gene at the maturation stage reflects the ancestral gnathostome situation, and provide new evidence in favor of the homology of enamel and enameloids in all gnathostomes.}, } @article {pmid30165815, year = {2018}, author = {Hagio-Izaki, K and Yasunaga, M and Yamaguchi, M and Kajiya, H and Morita, H and Yoneda, M and Hirofuji, T and Ohno, J}, title = {Lipopolysaccharide induces bacterial autophagy in epithelial keratinocytes of the gingival sulcus.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {18}, pmid = {30165815}, issn = {1471-2121}, support = {26463203//JSPS KAKENHI/International ; 18K09567//JSPS KAKENHI/International ; }, mesh = {Adenylate Kinase/metabolism ; Autophagosomes/drug effects/metabolism ; Autophagy/*drug effects ; Cells, Cultured ; Epithelial Cells/drug effects/*microbiology/*pathology ; Escherichia coli/metabolism ; Female ; Gingiva/*microbiology/*pathology ; Humans ; Keratinocytes/drug effects/*microbiology/*pathology ; Lipopolysaccharides/*pharmacology ; Male ; Microtubule-Associated Proteins/metabolism ; Porphyromonas gingivalis/physiology ; Reactive Oxygen Species/metabolism ; Signal Transduction ; Toll-Like Receptor 4/metabolism ; Up-Regulation/drug effects ; }, abstract = {BACKGROUND: Interactions of resident bacteria and/or their producing lipopolysaccharide (LPS) with sulcular epithelial keratinocytes may be regulated by autophagy in the gingival sulcus. In this study, we investigated an induction of bacterial autophagy in exfoliative sulcular keratinocytes of the gingival sulcus and cultured keratinocytes treated with Porphyromonas gingivalis-originated LPS (PgLPS).

RESULTS: Exfoliative sulcular keratinocytes showed an induction of autophagy, in addition to increased expression of LPS-mediated factors including lipopolysaccharide-binding protein and toll-like receptors (TLRs), leading to co-localization of bacteria with autophagosomes. In contrast, exfoliative keratinocytes from the free gingiva did not show similar autophagy. Autophagy activity in human cultured keratinocyte cells (HaCaT) was induced by PgLPS, which was dependent partially on the AMP-activated protein kinase (AMPK) pathway via increased intracellular reactive oxygen species (ROS) and was in association with an activation of TLR4 signaling. After incubation of cultured keratinocytes with E.coli BioParticles following PgLPS stimulation, co-localization of bioparticles with autophagosomes was enhanced. Conversely, blockage of autophagy with 3-methyladenin and LPS-binding with polymyxin B led to significant reduction of co-localization of particles with autophagosomes.

CONCLUSION: These findings indicate that PgLPS-induced autophagy is at least partially responsible for interaction between bacteria and sulcular keratinocytes in the gingival sulcus.}, } @article {pmid30165813, year = {2018}, author = {Rotimi, AM and Pierneef, R and Reva, ON}, title = {Selection of marker genes for genetic barcoding of microorganisms and binning of metagenomic reads by Barcoder software tools.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {309}, pmid = {30165813}, issn = {1471-2105}, support = {93664//National Research Foundation/ ; }, mesh = {Algorithms ; Bacteria/*genetics ; Base Sequence ; DNA Barcoding, Taxonomic/*methods ; *Genes, Bacterial ; Genetic Markers ; Humans ; Metagenome/genetics ; Metagenomics/*methods ; Microbiota/genetics ; Phylogeny ; ROC Curve ; Reproducibility of Results ; Sample Size ; *Software ; Species Specificity ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Metagenomic approaches have revealed the complexity of environmental microbiomes with the advancement in whole genome sequencing displaying a significant level of genetic heterogeneity on the species level. It has become apparent that patterns of superior bioactivity of bacteria applicable in biotechnology as well as the enhanced virulence of pathogens often requires distinguishing between closely related species or sub-species. Current methods for binning of metagenomic reads usually do not allow for identification below the genus level and generally stops at the family level.

RESULTS: In this work, an attempt was made to improve metagenomic binning resolution by creating genome specific barcodes based on the core and accessory genomes. This protocol was implemented in novel software tools available for use and download from http://bargene.bi.up.ac.za /. The most abundant barcode genes from the core genomes were found to encode for ribosomal proteins, certain central metabolic genes and ABC transporters. Performance of metabarcode sequences created by this package was evaluated using artificially generated and publically available metagenomic datasets. Furthermore, a program (Barcoding 2.0) was developed to align reads against barcode sequences and thereafter calculate various parameters to score the alignments and the individual barcodes. Taxonomic units were identified in metagenomic samples by comparison of the calculated barcode scores to set cut-off values. In this study, it was found that varying sample sizes, i.e. number of reads in a metagenome and metabarcode lengths, had no significant effect on the sensitivity and specificity of the algorithm. Receiver operating characteristics (ROC) curves were calculated for different taxonomic groups based on the results of identification of the corresponding genomes in artificial metagenomic datasets. The reliability of distinguishing between species of the same genus or family by the program was nearly perfect.

CONCLUSIONS: The results showed that the novel online tool BarcodeGenerator (http://bargene.bi.up.ac.za /) is an efficient approach for generating barcode sequences from a set of complete genomes provided by users. Another program, Barcoder 2.0 is available from the same resource to enable an efficient and practical use of metabarcodes for visualization of the distribution of organisms of interest in environmental and clinical samples.}, } @article {pmid30165812, year = {2018}, author = {Monson, MS and Van Goor, AG and Ashwell, CM and Persia, ME and Rothschild, MF and Schmidt, CJ and Lamont, SJ}, title = {Immunomodulatory effects of heat stress and lipopolysaccharide on the bursal transcriptome in two distinct chicken lines.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {643}, pmid = {30165812}, issn = {1471-2164}, support = {2011-67003-30228//National Institute of Food and Agriculture/ ; Hatch project 5358//National Institute of Food and Agriculture/ ; }, mesh = {Animals ; Birnaviridae Infections/drug therapy/immunology/*veterinary/virology ; Bursa of Fabricius/immunology/metabolism/virology ; Chickens/*genetics/*immunology ; Gene Expression Regulation ; Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing ; Hot Temperature ; Immunologic Factors/*pharmacology ; Lipopolysaccharides/*immunology ; Poultry Diseases/*genetics/immunology/virology ; Transcriptome ; }, abstract = {BACKGROUND: Exposure to heat stress suppresses poultry immune responses, which can increase susceptibility to infectious diseases and, thereby, intensify the negative effects of heat on poultry welfare and performance. Identifying genes and pathways that are affected by high temperatures, especially heat-induced changes in immune responses, could provide targets to improve disease resistance in chickens. This study utilized RNA-sequencing (RNA-seq) to investigate transcriptome responses in the bursa of Fabricius, a primary immune tissue, after exposure to acute heat stress and/or subcutaneous immune stimulation with lipopolysaccharide (LPS) in a 2 × 2 factorial design: Thermoneutral + Saline, Heat + Saline, Thermoneutral + LPS and Heat + LPS. All treatments were investigated in two chicken lines: a relatively heat- and disease-resistant Fayoumi line and a more susceptible broiler line.

RESULTS: Differential expression analysis determined that Heat + Saline had limited impact on gene expression (N = 1 or 63 genes) in broiler or Fayoumi bursa. However, Thermoneutral + LPS and Heat + LPS generated many expression changes in Fayoumi bursa (N = 368 and 804 genes). Thermoneutral + LPS was predicted to increase immune-related cell signaling and cell migration, while Heat + LPS would activate mortality-related functions and decrease expression in WNT signaling pathways. Further inter-treatment comparisons in the Fayoumi line revealed that heat stress prevented many of the expression changes caused by LPS. Although fewer significant expression changes were observed in the broiler bursa after exposure to Thermoneutral + LPS (N = 59 genes) or to Heat + LPS (N = 146 genes), both treatments were predicted to increase cell migration. Direct comparison between lines (broiler to Fayoumi) confirmed that each line had distinct responses to treatment.

CONCLUSIONS: Transcriptome analysis identified genes and pathways involved in bursal responses to heat stress and LPS and elucidated that these effects were greatest in the combined treatment. The interaction between heat and LPS was line dependent, with suppressive expression changes primarily in the Fayoumi line. Potential target genes, especially those involved in cell migration and immune signaling, can inform future research on heat stress in poultry and could prove useful for improving disease resistance.}, } @article {pmid30165811, year = {2018}, author = {Wee, BA and Tai, AS and Sherrard, LJ and Ben Zakour, NL and Hanks, KR and Kidd, TJ and Ramsay, KA and Lamont, I and Whiley, DM and Bell, SC and Beatson, SA}, title = {Whole genome sequencing reveals the emergence of a Pseudomonas aeruginosa shared strain sub-lineage among patients treated within a single cystic fibrosis centre.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {644}, pmid = {30165811}, issn = {1471-2164}, support = {45919//National Health and Medical Research Council/ ; 1090456//National Health and Medical Research Council/ ; 1088448//National Health and Medical Research Council/ ; }, mesh = {Adult ; Cystic Fibrosis/*complications/microbiology ; Genetic Variation ; Genotype ; Humans ; Phylogeny ; Pseudomonas Infections/*microbiology/*transmission ; Pseudomonas aeruginosa/*classification/genetics/*isolation & purification ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Chronic lung infections caused by Pseudomonas aeruginosa are a significant cause of morbidity and mortality in people with cystic fibrosis (CF). Shared P. aeruginosa strains, that can be transmitted between patients, are of concern and in Australia the AUST-02 shared strain is predominant in individuals attending CF centres in Queensland and Western Australia. M3L7 is a multidrug resistant sub-type of AUST-02 that was recently identified in a Queensland CF centre and was shown to be associated with poorer clinical outcomes. The main aim of this study was to resolve the relationship of the emergent M3L7 sub-type within the AUST-02 group of strains using whole genome sequencing.

RESULTS: A whole genome core phylogeny of 63 isolates indicated that M3L7 is a monophyletic sub-lineage within the context of the broader AUST-02 group. Relatively short branch lengths connected all of the M3L7 isolates. A phylogeny based on nucleotide polymorphisms present across the genome showed that the chronological estimation of the most recent common ancestor was around 2001 (± 3 years). SNP differences between sequential non-hypermutator M3L7 isolates collected 3-4 years apart from five patients suggested both continuous infection of the same strain and cross-infection of some M3L7 variants between patients. The majority of polymorphisms that were characteristic of M3L7 (i.e. acquired after divergence from all other AUST-02 isolates sequenced) were found to produce non-synonymous mutations in virulence and antibiotic resistance genes.

CONCLUSIONS: M3L7 has recently diverged from a common ancestor, indicating descent from a single carrier at a CF treatment centre in Australia. Both adaptation to the lung and transmission of M3L7 between adults attending this centre may have contributed to its rapid dissemination. Further genomic investigations are required on multiple intra-sample isolates of this sub-type to decipher potential mechanisms which facilitates its epidemiological success.}, } @article {pmid30165810, year = {2018}, author = {Galen, SC and Nunes, R and Sweet, PR and Perkins, SL}, title = {Integrating coalescent species delimitation with analysis of host specificity reveals extensive cryptic diversity despite minimal mitochondrial divergence in the malaria parasite genus Leucocytozoon.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {128}, pmid = {30165810}, issn = {1471-2148}, support = {1358465//National Science Foundation/International ; }, mesh = {Animals ; Cytochromes b/genetics ; DNA, Mitochondrial/genetics ; Genetic Loci ; *Genetic Variation ; Haemosporida/*genetics ; Haplotypes/genetics ; *Host Specificity ; Malaria/*parasitology ; Mitochondria/*genetics ; Parasites/*genetics ; Phylogeny ; Songbirds/parasitology ; Species Specificity ; }, abstract = {BACKGROUND: Coalescent methods that use multi-locus sequence data are powerful tools for identifying putatively reproductively isolated lineages, though this approach has rarely been used for the study of microbial groups that are likely to harbor many unrecognized species. Among microbial symbionts, integrating genetic species delimitation methods with trait data that could indicate reproductive isolation, such as host specificity data, has rarely been used despite its potential to inform species limits. Here we test the ability of an integrative approach combining genetic and host specificity data to delimit species within the avian malaria parasite genus Leucocytozoon in central Alaska.

RESULTS: We sequenced seven nuclear loci for 69 Leucocytozoon samples and used multiple species delimitation methods (GMYC and BPP models), tested for differences in host infection patterns among putative species based on 406 individual infections, and characterized parasite morphology. We found that cryptic morphology has masked a highly diverse Leucocytozoon assemblage, with most species delimitation methods recovering support for at least 21 separate species that occur sympatrically and have divergent host infection patterns. Reproductive isolation among putative species appears to have evolved despite low mtDNA divergence, and in one instance two Leucocytozoon cytb haplotypes that differed by a single base pair (~ 0.2% divergence) were supported as separate species. However, there was no consistent association between mtDNA divergence and species limits. Among cytb haplotypes that differed by one to three base pairs we observed idiosyncratic patterns of nuclear and ecological divergence, with cytb haplotype pairs found to be either conspecific, reproductively isolated with no divergence in host specificity, or reproductively isolated with divergent patterns of host specialization.

CONCLUSION: Integrating multi-locus genetic species delimitation methods and non-traditional ecological data types such as host specificity provide a novel view of the diversity of avian malaria parasites that has been missed previously using morphology and mtDNA barcodes. Species delimitation methods show that Leucocytozoon is highly species-rich in Alaska, and the genus is likely to harbor extraordinary species-level diversity worldwide. Integrating genetic and ecological data will be an important approach for understanding the diversity and evolutionary history of microbial symbionts moving forward.}, } @article {pmid30165699, year = {2018}, author = {Calarco, L and Barratt, J and Ellis, J}, title = {Genome Wide Identification of Mutational Hotspots in the Apicomplexan Parasite Neospora caninum and the Implications for Virulence.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2417-2431}, pmid = {30165699}, issn = {1759-6653}, abstract = {Neospora caninum is an apicomplexan parasite responsible for neosporosis, a disease causing hind limb paralysis in dogs and abortion in cattle, resulting in substantial economic losses to beef and dairy industries. Marked differences in pathogenicity exist between N. caninum strains suggesting that intrinsic genetic differences exist between them. These differences likely exist in genes expressed during the tachyzoite lifecycle stage which is responsible for the pathogenesis of neosporosis. An improved understanding of these genetic differences is essential to understanding N. caninum virulence, though such knowledge is scarce. Using a variant detection workflow we compared the tachyzoite transcriptomes of two N. caninum strains with different virulence properties: NC-Liverpool (virulent) and NC-Nowra (avirulent). This workflow identified 3130 SNPs and 6123 indels between the strains, and nine markers capturing 30 variants were Sanger sequenced for both strains. Sequencing of these loci was extended to an additional eight strains and subsequent phylogenetic analysis supported a genetic population structure comprised of two major clades with no geographical segregation. Sequence polymorphisms within coding regions of tachyzoite-associated genes were concentrated on chromosomes XI and XII, with 19 distinct tachyzoite-associated SNP hotspot regions identified within coding regions of the N. caninum nuclear genome. The variants were predominantly located in loci associated with protein binding, protein-protein interactions, transcription, and translation. Furthermore, 468 nonsynonymous SNPs identified within protein-coding genes were associated with protein kinase activity, protein binding, protein phosphorylation, and proteolysis. This work may implicate these processes and the specific proteins involved as novel effectors of N. caninum tachyzoite virulence.}, } @article {pmid30165640, year = {2018}, author = {Higgins, SA and Schadt, CW and Matheny, PB and Löffler, FE}, title = {Phylogenomics Reveal the Dynamic Evolution of Fungal Nitric Oxide Reductases and Their Relationship to Secondary Metabolism.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2474-2489}, pmid = {30165640}, issn = {1759-6653}, abstract = {Fungi expressing P450nor, an unconventional nitric oxide (NO) reducing cytochrome P450, are considered significant contributors to environmental nitrous oxide (N2O) emissions. Despite extensive efforts, fungal contributions to N2O emissions remain uncertain. For example, the majority of N2O emitted from antibiotic-amended soil microcosms is attributed to fungal activity, yet axenic fungal cultures do not couple N-oxyanion respiration to growth and these fungi produce only minor quantities of N2O. To assist in reconciling these conflicting observations and produce a benchmark genomic analysis of fungal denitrifiers, genes underlying denitrification were examined in >700 fungal genomes. Of 167 p450nor-containing genomes identified, 0, 30, and 48 also harbored the denitrification genes narG, napA, or nirK, respectively. Compared with napA and nirK, p450nor was twice as abundant and exhibited 2-5-fold more gene duplications, losses, and transfers, indicating a disconnect between p450nor presence and denitrification potential. Furthermore, cooccurrence of p450nor with genes encoding NO-detoxifying flavohemoglobins (Spearman r = 0.87, p = 1.6e-10) confounds hypotheses regarding P450nor's primary role in NO detoxification. Instead, ancestral state reconstruction united P450nor with actinobacterial cytochrome P450s (CYP105) involved in secondary metabolism (SM) and 19 (11%) p450nor-containing genomic regions were predicted to be SM clusters. Another 40 (24%) genomes harbored genes nearby p450nor predicted to encode hallmark SM functions, providing additional contextual evidence linking p450nor to SM. These findings underscore the potential physiological implications of widespread p450nor gene transfer, support the undiscovered affiliation of p450nor with fungal SM, and challenge the hypothesis of p450nor's primary role in denitrification.}, } @article {pmid30165630, year = {2018}, author = {Abbas, AH and Silva Pereira, S and D'Archivio, S and Wickstead, B and Morrison, LJ and Hall, N and Hertz-Fowler, C and Darby, AC and Jackson, AP}, title = {The Structure of a Conserved Telomeric Region Associated with Variant Antigen Loci in the Blood Parasite Trypanosoma congolense.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2458-2473}, pmid = {30165630}, issn = {1759-6653}, support = {BB/M022811/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J01477X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {African trypanosomiasis is a vector-borne disease of humans and livestock caused by African trypanosomes (Trypanosoma spp.). Survival in the vertebrate bloodstream depends on antigenic variation of Variant Surface Glycoproteins (VSGs) coating the parasite surface. In T. brucei, a model for antigenic variation, monoallelic VSG expression originates from dedicated VSG expression sites (VES). Trypanosoma brucei VES have a conserved structure consisting of a telomeric VSG locus downstream of unique, repeat sequences, and an independent promoter. Additional protein-coding sequences, known as "Expression Site Associated Genes (ESAGs)", are also often present and are implicated in diverse, bloodstream-stage functions. Trypanosoma congolense is a related veterinary pathogen, also displaying VSG-mediated antigenic variation. A T. congolense VES has not been described, making it unclear if regulation of VSG expression is conserved between species. Here, we describe a conserved telomeric region associated with VSG loci from long-read DNA sequencing of two T. congolense strains, which consists of a distal repeat, conserved noncoding elements and other genes besides the VSG; although these are not orthologous to T. brucei ESAGs. Most conserved telomeric regions are associated with accessory minichromosomes, but the same structure may also be associated with megabase chromosomes. We propose that this region represents the T. congolense VES, and through comparison with T. brucei, we discuss the parallel evolution of antigenic switching mechanisms, and unique adaptation of the T. brucei VES for developmental regulation of bloodstream-stage genes. Hence, we provide a basis for understanding antigenic switching in T. congolense and the origins of the African trypanosome VES.}, } @article {pmid30165616, year = {2018}, author = {Robison, TA and Grusz, AL and Wolf, PG and Mower, JP and Fauskee, BD and Sosa, K and Schuettpelz, E}, title = {Mobile Elements Shape Plastome Evolution in Ferns.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2558-2571}, pmid = {30165616}, issn = {1759-6653}, abstract = {Plastid genomes display remarkable organizational stability over evolutionary time. From green algae to angiosperms, most plastid genomes are largely collinear, with only a few cases of inversion, gene loss, or, in extremely rare cases, gene addition. These plastome insertions are mostly clade-specific and are typically of nuclear or mitochondrial origin. Here, we expand on these findings and present the first family-level survey of plastome evolution in ferns, revealing a novel suite of dynamic mobile elements. Comparative plastome analyses of the Pteridaceae expose several mobile open reading frames that vary in sequence length, insertion site, and configuration among sampled taxa. Even between close relatives, the presence and location of these elements is widely variable when viewed in a phylogenetic context. We characterize these elements and refer to them collectively as Mobile Open Reading Frames in Fern Organelles (MORFFO). We further note that the presence of MORFFO is not restricted to Pteridaceae, but is found across ferns and other plant clades. MORFFO elements are regularly associated with inversions, intergenic expansions, and changes to the inverted repeats. They likewise appear to be present in mitochondrial and nuclear genomes of ferns, indicating that they can move between genomic compartments with relative ease. The origins and functions of these mobile elements are unknown, but MORFFO appears to be a major driver of structural genome evolution in the plastomes of ferns, and possibly other groups of plants.}, } @article {pmid30165589, year = {2018}, author = {Ranwez, V and Douzery, EJP and Cambon, C and Chantret, N and Delsuc, F}, title = {MACSE v2: Toolkit for the Alignment of Coding Sequences Accounting for Frameshifts and Stop Codons.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2582-2584}, pmid = {30165589}, issn = {1537-1719}, abstract = {Multiple sequence alignment is a prerequisite for many evolutionary analyses. Multiple Alignment of Coding Sequences (MACSE) is a multiple sequence alignment program that explicitly accounts for the underlying codon structure of protein-coding nucleotide sequences. Its unique characteristic allows building reliable codon alignments even in the presence of frameshifts. This facilitates downstream analyses such as selection pressure estimation based on the ratio of nonsynonymous to synonymous substitutions. Here, we present MACSE v2, a major update with an improved version of the initial algorithm enriched with a complete toolkit to handle multiple alignments of protein-coding sequences. A graphical interface now provides user-friendly access to the different subprograms.}, } @article {pmid30165560, year = {2018}, author = {Thorpe, P and Escudero-Martinez, CM and Cock, PJA and Eves-van den Akker, S and Bos, JIB}, title = {Shared Transcriptional Control and Disparate Gain and Loss of Aphid Parasitism Genes.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2716-2733}, pmid = {30165560}, issn = {1759-6653}, support = {BB/M014207/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Aphids are a diverse group of taxa that contain agronomically important species, which vary in their host range and ability to infest crop plants. The genome evolution underlying agriculturally important aphid traits is not well understood. We generated draft genome assemblies for two aphid species: Myzus cerasi (black cherry aphid) and the cereal specialist Rhopalosiphum padi. Using a de novo gene prediction pipeline on both these, and three additional aphid genome assemblies (Acyrthosiphon pisum, Diuraphis noxia, and Myzus persicae), we show that aphid genomes consistently encode similar gene numbers. We compare gene content, gene duplication, synteny, and putative effector repertoires between these five species to understand the genome evolution of globally important plant parasites. Aphid genomes show signs of relatively distant gene duplication, and substantial, relatively recent, gene birth. Putative effector repertoires, originating from duplicated and other loci, have an unusual genomic organization and evolutionary history. We identify a highly conserved effector pair that is tightly physically linked in the genomes of all aphid species tested. In R. padi, this effector pair is tightly transcriptionally linked and shares an unknown transcriptional control mechanism with a subset of ∼50 other putative effectors and secretory proteins. This study extends our current knowledge on the evolution of aphid genomes and reveals evidence for an as-of-yet unknown shared control mechanism, which underlies effector expression, and ultimately plant parasitism.}, } @article {pmid30165545, year = {2018}, author = {Simão, MC and Haudry, A and Granzotto, A and de Setta, N and Carareto, CMA}, title = {Helena and BS: Two Travellers between the Genera Drosophila and Zaprionus.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2671-2685}, pmid = {30165545}, issn = {1759-6653}, abstract = {The frequency of horizontal transfers of transposable elements (HTTs) varies among the types of elements according to the transposition mode and the geographical and temporal overlap of the species involved in the transfer. The drosophilid species of the genus Zaprionus and those of the melanogaster, obscura, repleta, and virilis groups of the genus Drosophila investigated in this study shared space and time at some point in their evolutionary history. This is particularly true of the subgenus Zaprionus and the melanogaster subgroup, which overlapped both geographically and temporally in Tropical Africa during their period of origin and diversification. Here, we tested the hypothesis that this overlap may have facilitated the transfer of retrotransposons without long terminal repeats (non-LTRs) between these species. We estimated the HTT frequency of the non-LTRs BS and Helena at the genome-wide scale by using a phylogenetic framework and a vertical and horizontal inheritance consistence analysis (VHICA). An excessively low synonymous divergence among distantly related species and incongruities between the transposable element and species phylogenies allowed us to propose at least four relatively recent HTT events of Helena and BS involving ancestors of the subgroup melanogaster and ancestors of the subgenus Zaprionus during their concomitant diversification in Tropical Africa, along with older possible events between species of the subgenera Drosophila and Sophophora. This study provides the first evidence for HTT of non-LTRs retrotransposons between Drosophila and Zaprionus, including an in-depth reconstruction of the time frame and geography of these events.}, } @article {pmid30165514, year = {2018}, author = {Kimble, JC and Winter, AS and Spilde, MN and Sinsabaugh, RL and Northup, DE}, title = {A potential central role of Thaumarchaeota in N-Cycling in a semi-arid environment, Fort Stanton Cave, Snowy River passage, New Mexico, USA.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy173}, pmid = {30165514}, issn = {1574-6941}, abstract = {Low biomass and productivity of arid-land caves with limited availability of nitrogen (N) raises the question of how microbes acquire and cycle this essential element. Caves are ideal environments for investigating microbial functional capabilities, as they lack phototrophic activity and have near constant temperatures and high relative humidity. From the walls of Fort Stanton Cave (FSC), multicolored secondary mineral deposits of soil-like material low in fixed N, known as ferromanganese deposits (FMD), were collected. We hypothesized that within FMD samples we would find the presence of microbial N cycling genes and taxonomy related to N cycling microorganisms. Community DNA were sequenced using Illumina shotgun metagenomics and 16S rRNA gene sequencing. Results suggest a diverse N cycle encompassing several energetic pathways including nitrification, dissimilatory nitrate reduction and denitrification. N cycling genes associated with assimilatory nitrate reduction were also identified. Functional gene sequences and taxonomic findings suggest several bacterial and archaeal phyla potentially play a role in nitrification pathways in FSC and FMD. Thaumarchaeota, a deep-branching archaeal division, likely play an essential and possibly dominant role in the oxidation of ammonia. Our results provide genomic evidence for understanding how microbes are potentially able to acquire and cycle N in a low-nutrient subterranean environment.}, } @article {pmid30165492, year = {2018}, author = {Lin, YT and Tu, TH and Wei, CL and Rumble, D and Lin, LH and Wang, PL}, title = {Steep redox gradient and biogeochemical cycling driven by deeply sourced fluids and gases in a terrestrial mud volcano.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy171}, pmid = {30165492}, issn = {1574-6941}, abstract = {Mud volcanoes provide an accessible channel through which deep subsurface environments can be observed. The manner in which deeply sourced materials shape biogeochemical processes and microbial communities in such geological features remains largely unknown. This study characterized redox transitions, biogeochemical fluxes and microbial communities for samples collected from a methane-rich mud volcano in southwestern Taiwan. Our results indicated that oxygen penetration was confined within the upper 4 mm of fluids/muds and counteracted by the oxidation of pyrite, dissolved sulfide, methane and organic matter at various degrees. Beneath the oxic zone, anaerobic sulfur oxidation, sulfate reduction, anaerobic methanotrophy and methanogenesis were compartmentalized into different depths in the pool periphery, forming a metabolic network that efficiently cycles methane and sulfur. Community members affiliated with various Proteobacteria capable of aerobic oxidation of sulfur, methane and methyl compounds were more abundant in the anoxic zone with diminished sulfate and high methane. These findings suggest either the requirement of alternative electron acceptors or a persistent population that once flourished in the oxic zone. Overall, this study demonstrates the distribution pattern for a suite of oxidative and reductive metabolic reactions along a steep redox gradient imposed by deep fluids in a mud volcano ecosystem.}, } @article {pmid30165367, year = {2018}, author = {Chauhan, P and Rani, A and Singh, SK and Rai, AK}, title = {Complete Androgen Insensitivity Syndrome due to Mutations in the DNA-Binding Domain of the Human Androgen Receptor Gene.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000492261}, pmid = {30165367}, issn = {1661-5433}, abstract = {Androgen insensitivity syndrome (AIS) is an X-linked recessive disorder with a 46,XY karyotype caused by alterations in the androgen receptor (AR) gene. We have identified 2 mutations in the AR gene that resulted in complete androgen insensitivity syndrome (CAIS) in 2 unrelated cases. This study includes cytogenetics, hormonal, molecular, and bioinformatics analysis including sequencing of the SRY (sex-determining region Y) and AR genes. Mutational analysis in the first case of primary amenorrhea revealed a novel nucleotide substitution (IVS2-2A>G) in the second intron of the AR gene. The mutation is located in the acceptor splice site (2 nucleotides before exon 3) and caused skipping of exon 3 and formation of an abnormal protein. The second mutation (g. 98762_98764delTCT) was identified in a case of oligoamenorrhea and caused the deletion of 1 amino acid (p.∆Phe583). Both identified mutations were located in the conserved P-box region of the DNA-binding domain which is responsible for base-specific contacts with the DNA major groove. Furthermore, a hormonal imbalance was also noticed in both cases with high levels of gonadotropins like FSH and LH in both cases. The present study concluded that both identified AR mutations are predicted to either abolish or decrease the binding ability of the AR to androgen response elements of its downstream genes.}, } @article {pmid30161294, year = {2018}, author = {}, title = {A year in the life of a thrombolite: comparative metatranscriptomics reveals dynamic metabolic changes over diel and seasonal cycles.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2670}, doi = {10.1111/1462-2920.14277}, pmid = {30161294}, issn = {1462-2920}, } @article {pmid30160987, year = {2018}, author = {Bošković, A and Rando, OJ}, title = {Transgenerational Epigenetic Inheritance.}, journal = {Annual review of genetics}, volume = {52}, number = {}, pages = {21-41}, doi = {10.1146/annurev-genet-120417-031404}, pmid = {30160987}, issn = {1545-2948}, abstract = {Inheritance of genomic DNA underlies the vast majority of biological inheritance, yet it has been clear for decades that additional epigenetic information can be passed on to future generations. Here, we review major model systems for transgenerational epigenetic inheritance via the germline in multicellular organisms. In addition to surveying examples of epivariation that may arise stochastically or in response to unknown stimuli, we also discuss the induction of heritable epigenetic changes by genetic or environmental perturbations. Mechanistically, we discuss the increasingly well-understood molecular pathways responsible for epigenetic inheritance, with a focus on the unusual features of the germline epigenome.}, } @article {pmid30160044, year = {2018}, author = {Zhan, Y and Chen, F}, title = {The smallest ssDNA phage infecting a marine bacterium.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14394}, pmid = {30160044}, issn = {1462-2920}, abstract = {In the marine environment, only a few lytic single-stranded DNA (ssDNA) phages have been isolated and characterized, despite the fact that diverse ssDNA bacteriophages have been discovered via metagenomic studies. In this study, we isolated and characterized a new ssDNA phage, vB_RpoMi-Mini, which infects a marine bacterium Ruegeria pomeroyi DSS-3. With a genome size of 4248 bp and only four putative open reading frames (ORF), vB_RpoMi-Mini becomes the smallest ssDNA phage among the known ssDNA phage isolates and represents the DNA bacteriophage with the least number of ORFs. Genome-wide analysis reveals that bacteriophage Mini is distantly related to the known ssDNA phages and belongs to an unclassified ssDNA phage within the Microviridae family. The presence of peptidase in vB_RpoMi-Mini genome further implies that horizontal gene transfer could be an important driving force in the evolution of ssDNA phages. Bacteriophage Mini seems to have lost the spike protein commonly seen in ssDNA phages, suggesting that ssDNA phage can be more diverse than previously thought. Metagenomic analysis indicates that Mini-like phages are widely distributed in the environments. The discovery of vB_RpoMi-Mini expands our understanding of ssDNA phages in nature, and also indicates our dearth of knowledge regarding of ssDNA phages.}, } @article {pmid30159999, year = {2018}, author = {Morán, XAG and Calvo-Díaz, A and Arandia-Gorostidi, N and Huete-Stauffer, TM}, title = {Temperature sensitivities of microbial plankton net growth rates are seasonally coherent and linked to nutrient availability.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3798-3810}, doi = {10.1111/1462-2920.14393}, pmid = {30159999}, issn = {1462-2920}, support = {//Spanish Ministerio de Economía y Competitividad through the COMITE/ ; }, abstract = {Recent work suggests that temperature effects on marine heterotrophic bacteria are strongly seasonal, but few attempts have been made to concurrently assess them across trophic levels. Here, we estimated the temperature sensitivities (using activation energies, E) of autotrophic and heterotrophic microbial plankton net growth rates over an annual cycle in NE Atlantic coastal waters. Phytoplankton grew in winter and late autumn (0.41 ± 0.16 SE d-1) and decayed in the remaining months (-0.42 ± 0.10 d-1). Heterotrophic microbes shared a similar seasonality, with positive net growth for bacteria (0.14-1.48 d-1), while nanoflagellates had higher values (> 0.4 d-1) in winter and spring relative to the rest of the year (-0.46 to 0.29 d-1). Net growth rates activation energies showed similar dynamics in the three groups (-1.07 to 1.51 eV), characterized by maxima in winter, minima in summer and resumed increases in autumn. Microbial plankton E values were significantly correlated with nitrate concentrations as a proxy for nutrient availability. Nutrient-sufficiency (i.e., > 1 μmol l-1 nitrate) resulted in significantly higher activation energies of phytoplankton and heterotrophic nanoflagellates relative to nutrient-limited conditions. We suggest that only within spatio-temporal windows of both moderate bottom-up and top-down controls will temperature have a major enhancing effect on microbial growth.}, } @article {pmid30159996, year = {2018}, author = {Xu, D and Sun, P and Zhang, Y and Li, R and Huang, B and Jiao, N and Warren, A and Wang, L}, title = {Pigmented microbial eukaryotes fuel the deep sea carbon pool in the tropical Western Pacific Ocean.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3811-3824}, doi = {10.1111/1462-2920.14396}, pmid = {30159996}, issn = {1462-2920}, support = {31772426//National Natural Science Foundation of China/ ; 41876142//National Natural Science Foundation of China/ ; 91751207//National Natural Science Foundation of China/ ; 2016YFA0601400//National Key Research Programs/ ; }, abstract = {Phototrophic microbial eukaryotes dominate primary production over large oceanic regions. Due to their small sizes and slow sinking rates, it is assumed they contribute relatively little to the downward export of organic carbon via the biological pump. Therefore, the community structure of phototrophic cells in the deep ocean has long been overlooked and remains largely unknown. In this study, we used an integrative approach, including epifluorescence microscopy, sequencing of 18S rRNA and photosystem-II psbA gene transcripts, to investigate phototrophic microbial eukaryotes in samples collected from the tropical Western Pacific Ocean. It was found that: (i) pigmented nano-sized eukaryotes (PNEs) are ubiquitous in the deep Western Pacific Ocean down to 5000 m depth; (ii) the PNE community is dominated by cells 2-5 μm in size; (iii) their abundance is significant, averaging 4 ± 1 (± s.e.) cells ml-1 in waters below 1000 m which is comparable to that of heterotrophic nanoflagellates; (iv) the active pigmented microbial eukaryotes in the deep waters are highly diverse and dominated by Haptophyta followed by Chlorophyta and Bacillariophyta; (v) PNEs in deep waters were likely transported from surface ocean by various fast-sinking mechanisms, thus contributing to the biological pump and fuelling the deep-sea communities by supplying fresh organic carbon.}, } @article {pmid30159978, year = {2018}, author = {Biessy, A and Filion, M}, title = {Phenazines in plant-beneficial Pseudomonas spp.: biosynthesis, regulation, function and genomics.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3905-3917}, doi = {10.1111/1462-2920.14395}, pmid = {30159978}, issn = {1462-2920}, abstract = {Plant-beneficial phenazine-producing Pseudomonas spp. are proficient biocontrol agents of soil-dwelling plant pathogens. Phenazines are redox-active molecules that display broad-spectrum antibiotic activity toward many fungal, bacterial and oomycete plant pathogens. Phenazine compounds also play a role in the persistence and survival of Pseudomonas spp. in the rhizosphere. This mini-review focuses on plant-beneficial phenazine-producing Pseudomonas spp. from the P. fluorescens species complex, which includes numerous well-known phenazine-producing strains of biocontrol interest. In this review the current knowledge on phenazine biosynthesis and regulation, the role played by phenazines in biocontrol and rhizosphere colonization, as well as exciting new advances in the genomics of plant-beneficial phenazine-producing Pseudomonas spp. will be discussed.}, } @article {pmid30159142, year = {2018}, author = {Manus, MB}, title = {Evolutionary mismatch.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {190-191}, pmid = {30159142}, issn = {2050-6201}, } @article {pmid30158708, year = {2018}, author = {Dick, RA and Zadrozny, KK and Xu, C and Schur, FKM and Lyddon, TD and Ricana, CL and Wagner, JM and Perilla, JR and Ganser-Pornillos, BK and Johnson, MC and Pornillos, O and Vogt, VM}, title = {Author Correction: Inositol phosphates are assembly co-factors for HIV-1.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {E22}, doi = {10.1038/s41586-018-0505-4}, pmid = {30158708}, issn = {1476-4687}, abstract = {In this Letter, the Protein Data Bank (PDB) accessions were incorrectly listed as '6BH5, 6BHT and 6BHS' instead of '6BHR, 6BHT and 6BHS'; this has been corrected online.}, } @article {pmid30158707, year = {2018}, author = {Eelen, G and Dubois, C and Cantelmo, AR and Goveia, J and Brüning, U and DeRan, M and Jarugumilli, G and van Rijssel, J and Saladino, G and Comitani, F and Zecchin, A and Rocha, S and Chen, R and Huang, H and Vandekeere, S and Kalucka, J and Lange, C and Morales-Rodriguez, F and Cruys, B and Treps, L and Ramer, L and Vinckier, S and Brepoels, K and Wyns, S and Souffreau, J and Schoonjans, L and Lamers, WH and Wu, Y and Haustraete, J and Hofkens, J and Liekens, S and Cubbon, R and Ghesquière, B and Dewerchin, M and Gervasio, FL and Li, X and van Buul, JD and Wu, X and Carmeliet, P}, title = {Role of glutamine synthetase in angiogenesis beyond glutamine synthesis.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {63-69}, doi = {10.1038/s41586-018-0466-7}, pmid = {30158707}, issn = {1476-4687}, mesh = {Actins/metabolism ; Animals ; Cell Movement ; Endothelial Cells/*enzymology/metabolism/*pathology ; Female ; Glutamate-Ammonia Ligase/deficiency/genetics/*metabolism/physiology ; Glutamine/*biosynthesis ; HEK293 Cells ; Human Umbilical Vein Endothelial Cells/cytology/enzymology/metabolism ; Humans ; Lipoylation ; Mice ; *Neovascularization, Pathologic ; Palmitic Acid/metabolism ; Protein Processing, Post-Translational ; Stress Fibers/metabolism ; rho GTP-Binding Proteins/chemistry/metabolism ; rho-Associated Kinases/metabolism ; }, abstract = {Glutamine synthetase, encoded by the gene GLUL, is an enzyme that converts glutamate and ammonia to glutamine. It is expressed by endothelial cells, but surprisingly shows negligible glutamine-synthesizing activity in these cells at physiological glutamine levels. Here we show in mice that genetic deletion of Glul in endothelial cells impairs vessel sprouting during vascular development, whereas pharmacological blockade of glutamine synthetase suppresses angiogenesis in ocular and inflammatory skin disease while only minimally affecting healthy adult quiescent endothelial cells. This relies on the inhibition of endothelial cell migration but not proliferation. Mechanistically we show that in human umbilical vein endothelial cells GLUL knockdown reduces membrane localization and activation of the GTPase RHOJ while activating other Rho GTPases and Rho kinase, thereby inducing actin stress fibres and impeding endothelial cell motility. Inhibition of Rho kinase rescues the defect in endothelial cell migration that is induced by GLUL knockdown. Notably, glutamine synthetase palmitoylates itself and interacts with RHOJ to sustain RHOJ palmitoylation, membrane localization and activation. These findings reveal that, in addition to the known formation of glutamine, the enzyme glutamine synthetase shows unknown activity in endothelial cell migration during pathological angiogenesis through RHOJ palmitoylation.}, } @article {pmid30158706, year = {2018}, author = {Falcon, B and Zhang, W and Murzin, AG and Murshudov, G and Garringer, HJ and Vidal, R and Crowther, RA and Ghetti, B and Scheres, SHW and Goedert, M}, title = {Structures of filaments from Pick's disease reveal a novel tau protein fold.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {137-140}, pmid = {30158706}, issn = {1476-4687}, support = {P30 AG010133/AG/NIA NIH HHS/United States ; }, abstract = {The ordered assembly of tau protein into abnormal filamentous inclusions underlies many human neurodegenerative diseases1. Tau assemblies seem to spread through specific neural networks in each disease2, with short filaments having the greatest seeding activity3. The abundance of tau inclusions strongly correlates with disease symptoms4. Six tau isoforms are expressed in the normal adult human brain-three isoforms with four microtubule-binding repeats each (4R tau) and three isoforms that lack the second repeat (3R tau)1. In various diseases, tau filaments can be composed of either 3R or 4R tau, or of both. Tau filaments have distinct cellular and neuroanatomical distributions5, with morphological and biochemical differences suggesting that they may be able to adopt disease-specific molecular conformations6,7. Such conformers may give rise to different neuropathological phenotypes8,9, reminiscent of prion strains10. However, the underlying structures are not known. Using electron cryo-microscopy, we recently reported the structures of tau filaments from patients with Alzheimer's disease, which contain both 3R and 4R tau11. Here we determine the structures of tau filaments from patients with Pick's disease, a neurodegenerative disorder characterized by frontotemporal dementia. The filaments consist of residues Lys254-Phe378 of 3R tau, which are folded differently from the tau filaments in Alzheimer's disease, establishing the existence of conformers of assembled tau. The observed tau fold in the filaments of patients with Pick's disease explains the selective incorporation of 3R tau in Pick bodies, and the differences in phosphorylation relative to the tau filaments of Alzheimer's disease. Our findings show how tau can adopt distinct folds in the human brain in different diseases, an essential step for understanding the formation and propagation of molecular conformers.}, } @article {pmid30158705, year = {2018}, author = {Hopkins, BD and Pauli, C and Du, X and Wang, DG and Li, X and Wu, D and Amadiume, SC and Goncalves, MD and Hodakoski, C and Lundquist, MR and Bareja, R and Ma, Y and Harris, EM and Sboner, A and Beltran, H and Rubin, MA and Mukherjee, S and Cantley, LC}, title = {Publisher Correction: Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {E24}, doi = {10.1038/s41586-018-0506-3}, pmid = {30158705}, issn = {1476-4687}, abstract = {In this Letter, author Xing Du was incorrectly listed as Du Xing; this has been corrected online.}, } @article {pmid30158704, year = {2018}, author = {Fulde, M and Sommer, F and Chassaing, B and van Vorst, K and Dupont, A and Hensel, M and Basic, M and Klopfleisch, R and Rosenstiel, P and Bleich, A and Bäckhed, F and Gewirtz, AT and Hornef, MW}, title = {Publisher Correction: Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition.}, journal = {Nature}, volume = {563}, number = {7731}, pages = {E25}, doi = {10.1038/s41586-018-0507-2}, pmid = {30158704}, issn = {1476-4687}, abstract = {In Fig. 1d of this Letter, the third group along should have been labelled 'WT' rather than 'Tlr5'. This has been corrected online.}, } @article {pmid30158703, year = {2018}, author = {Wang, PY and Mason, TG}, title = {A Brownian quasi-crystal of pre-assembled colloidal Penrose tiles.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {94-99}, doi = {10.1038/s41586-018-0464-9}, pmid = {30158703}, issn = {1476-4687}, abstract = {Penrose's pentagonal P2 quasi-crystal1-4 is a beautiful, hierarchically organized multiscale structure in which kite- and dart-shaped tiles are arranged into local motifs, such as pentagonal stars, which are in turn arranged into various close-packed superstructural patterns that become increasingly complex at larger length scales. Although certain types of quasi-periodic structure have been observed in hard and soft matter, such structures are difficult to engineer, especially over large areas, because generating the necessary, highly specific interactions between constituent building blocks is challenging. Previously reported soft-matter quasi-crystals of dendrimers5, triblock copolymers6, nanoparticles7 and polymeric micelles8 have been limited to 12- or 18-fold symmetries. Because routes for self-assembling complex colloidal building blocks9-11 into low-defect dynamic superstructures remain limited12, alternative methods, such as using optical and directed assembly, are being explored13,14. Holographic laser tweezers15 and optical standing waves16 have been used to hold microspheres in local quasi-crystalline arrangements, and magnetic microspheres of two different sizes have been assembled into local five-fold-symmetric quasi-crystalline arrangements in two dimensions17. But a Penrose quasi-crystal of mobile colloidal tiles has hitherto not been fabricated over large areas. Here we report such a quasi-crystal in two dimensions, created using a highly parallelizable method of lithographic printing and subsequent release of pre-assembled kite- and dart-shaped tiles into a solution-dispersion containing a depletion agent. After release, the positions and orientations of the tiles within the quasi-crystal can fluctuate, and these tiles undergo random, Brownian motion in the monolayer owing to frequent collisions between neighbouring tiles, even after the system reaches equilibrium. Using optical microscopy, we study both the equilibrium fluctuations of the system at high tile densities and also the 'melting' of the pattern as the tile density is lowered. At high tile densities we find signatures of a five-fold pentatic liquid quasi-crystalline phase, analogous to a six-fold hexatic liquid crystal. Our fabrication approach is applicable to tiles of different sizes and shapes, and with different initial positions and orientations, enabling the creation of two-dimensional quasi-crystalline systems (and other systems that possess multiscale complexity at high tile densities) beyond those of current self- or directed-assembly methods18-20. We anticipate that our approach for generating lithographically pre-assembled monolayers could be extended to create three-dimensional Brownian systems of fluctuating particles with custom-designed shapes through holographic lithography21,22 or stereolithography23.}, } @article {pmid30158702, year = {2018}, author = {Marshall, F and Reid, REB and Goldstein, S and Storozum, M and Wreschnig, A and Hu, L and Kiura, P and Shahack-Gross, R and Ambrose, SH}, title = {Ancient herders enriched and restructured African grasslands.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {387-390}, doi = {10.1038/s41586-018-0456-9}, pmid = {30158702}, issn = {1476-4687}, support = {ECS-0335765//National Science Foundation/International ; }, abstract = {Grasslands are one of the world's most extensive terrestrial biomes and are central to the survival of herders, their livestock and diverse communities of large wild mammals1-3. In Africa, tropical soils are predominantly nutrient-limited4-6 but productive grassy patches in wooded grassland savannah ecosystems2,4 grow on fertile soils created by geologic and edaphic factors, megafauna, fire and termites4-6. Mobile pastoralists also create soil-fertility hotspots by penning their herds at night, which concentrates excrement-and thus nutrients-from grazing of the surrounding savannahs7-11. Historical anthropogenic hotspots produce high-quality forage, attract wildlife and increase spatial heterogeneity in African savannahs4,12-15. Archaeological research suggests this effect extends back at least 1,000 years16-19 but little is known about nutrient persistence at millennial scales. Here we use chemical, isotopic and sedimentary analyses to show high nutrient and 15N enrichment in on-site degraded dung deposits relative to off-site soils at five Pastoral Neolithic20 sites (radiocarbon dated to between 3,700 and 1,550 calibrated years before present (cal. BP)). This study demonstrates the longevity of nutrient hotspots and the long-term legacy of ancient herders, whose settlements enriched and diversified African savannah landscapes over three millennia.}, } @article {pmid30158701, year = {2018}, author = {Hoffman, EA and Rowe, TB}, title = {Jurassic stem-mammal perinates and the origin of mammalian reproduction and growth.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {104-108}, doi = {10.1038/s41586-018-0441-3}, pmid = {30158701}, issn = {1476-4687}, abstract = {Transformations in morphology, physiology and behaviour along the mammalian stem lineage were accompanied by profound modifications to reproduction and growth, including the emergence of a reproductive strategy characterized by high maternal investment in a small number of offspring1,2 and heterochronic changes in early cranial development associated with the enlargement of the brain3. Because direct fossil evidence of these transitions is lacking, the timing and sequence of these modifications are unknown. Here we present what is, to our knowledge, the first fossil record of pre- or near-hatching young of any non-mammalian synapsid. A large clutch of well-preserved perinates of the tritylodontid Kayentatherium wellesi (Cynodontia, Mammaliamorpha) was found with a presumed maternal skeleton in Early Jurassic sediments of the Kayenta Formation. The single clutch comprises at least 38 individuals, well outside the range of litter sizes documented in extant mammals. This discovery confirms that production of high numbers of offspring represents the ancestral condition for amniotes, and also constrains the timing of a reduction in clutch size along the mammalian stem. Although tiny, the perinates have an overall skull shape that is similar to that of adults, with no allometric lengthening of the face during ontogeny. The only positive allometries are associated with the bones that support the masticatory musculature. Kayentatherium diverged just before a hypothesized pulse of brain expansion that reorganized cranial architecture at the base of Mammaliaformes4-6. The association of a high number of offspring and largely isometric cranial growth in Kayentatherium is consistent with a scenario in which encephalization-and attendant shifts in metabolism and development7,8-drove later changes to mammalian reproduction.}, } @article {pmid30158700, year = {2018}, author = {Shiber, A and Döring, K and Friedrich, U and Klann, K and Merker, D and Zedan, M and Tippmann, F and Kramer, G and Bukau, B}, title = {Cotranslational assembly of protein complexes in eukaryotes revealed by ribosome profiling.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {268-272}, doi = {10.1038/s41586-018-0462-y}, pmid = {30158700}, issn = {1476-4687}, abstract = {The folding of newly synthesized proteins to the native state is a major challenge within the crowded cellular environment, as non-productive interactions can lead to misfolding, aggregation and degradation1. Cells cope with this challenge by coupling synthesis with polypeptide folding and by using molecular chaperones to safeguard folding cotranslationally2. However, although most of the cellular proteome forms oligomeric assemblies3, little is known about the final step of folding: the assembly of polypeptides into complexes. In prokaryotes, a proof-of-concept study showed that the assembly of heterodimeric luciferase is an organized cotranslational process that is facilitated by spatially confined translation of the subunits encoded on a polycistronic mRNA4. In eukaryotes, however, fundamental differences-such as the rarity of polycistronic mRNAs and different chaperone constellations-raise the question of whether assembly is also coordinated with translation. Here we provide a systematic and mechanistic analysis of the assembly of protein complexes in eukaryotes using ribosome profiling. We determined the in vivo interactions of the nascent subunits from twelve hetero-oligomeric protein complexes of Saccharomyces cerevisiae at near-residue resolution. We find nine complexes assemble cotranslationally; the three complexes that do not show cotranslational interactions are regulated by dedicated assembly chaperones5-7. Cotranslational assembly often occurs uni-directionally, with one fully synthesized subunit engaging its nascent partner subunit, thereby counteracting its propensity for aggregation. The onset of cotranslational subunit association coincides directly with the full exposure of the nascent interaction domain at the ribosomal tunnel exit. The action of the ribosome-associated Hsp70 chaperone Ssb8 is coordinated with assembly. Ssb transiently engages partially synthesized interaction domains and then dissociates before the onset of partner subunit association, presumably to prevent premature assembly interactions. Our study shows that cotranslational subunit association is a prevalent mechanism for the assembly of hetero-oligomers in yeast and indicates that translation, folding and the assembly of protein complexes are integrated processes in eukaryotes.}, } @article {pmid30158699, year = {2018}, author = {Tsao, A and Sugar, J and Lu, L and Wang, C and Knierim, JJ and Moser, MB and Moser, EI}, title = {Integrating time from experience in the lateral entorhinal cortex.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {57-62}, doi = {10.1038/s41586-018-0459-6}, pmid = {30158699}, issn = {1476-4687}, mesh = {Animals ; Behavior, Animal/*physiology ; Entorhinal Cortex/*cytology/*physiology ; Male ; Rats ; Rats, Long-Evans ; Time Factors ; }, abstract = {The encoding of time and its binding to events are crucial for episodic memory, but how these processes are carried out in hippocampal-entorhinal circuits is unclear. Here we show in freely foraging rats that temporal information is robustly encoded across time scales from seconds to hours within the overall population state of the lateral entorhinal cortex. Similarly pronounced encoding of time was not present in the medial entorhinal cortex or in hippocampal areas CA3-CA1. When animals' experiences were constrained by behavioural tasks to become similar across repeated trials, the encoding of temporal flow across trials was reduced, whereas the encoding of time relative to the start of trials was improved. The findings suggest that populations of lateral entorhinal cortex neurons represent time inherently through the encoding of experience. This representation of episodic time may be integrated with spatial inputs from the medial entorhinal cortex in the hippocampus, allowing the hippocampus to store a unified representation of what, where and when.}, } @article {pmid30158698, year = {2018}, author = {Anderson, MA and O'Shea, TM and Burda, JE and Ao, Y and Barlatey, SL and Bernstein, AM and Kim, JH and James, ND and Rogers, A and Kato, B and Wollenberg, AL and Kawaguchi, R and Coppola, G and Wang, C and Deming, TJ and He, Z and Courtine, G and Sofroniew, MV}, title = {Required growth facilitators propel axon regeneration across complete spinal cord injury.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {396-400}, pmid = {30158698}, issn = {1476-4687}, support = {F32 NS096858/NS/NINDS NIH HHS/United States ; P30 NS062691/NS/NINDS NIH HHS/United States ; R01 NS084030/NS/NINDS NIH HHS/United States ; R01 NS096294/NS/NINDS NIH HHS/United States ; }, abstract = {Transected axons fail to regrow across anatomically complete spinal cord injuries (SCI) in adults. Diverse molecules can partially facilitate or attenuate axon growth during development or after injury1-3, but efficient reversal of this regrowth failure remains elusive4. Here we show that three factors that are essential for axon growth during development but are attenuated or lacking in adults-(i) neuron intrinsic growth capacity2,5-9, (ii) growth-supportive substrate10,11 and (iii) chemoattraction12,13-are all individually required and, in combination, are sufficient to stimulate robust axon regrowth across anatomically complete SCI lesions in adult rodents. We reactivated the growth capacity of mature descending propriospinal neurons with osteopontin, insulin-like growth factor 1 and ciliary-derived neurotrophic factor before SCI14,15; induced growth-supportive substrates with fibroblast growth factor 2 and epidermal growth factor; and chemoattracted propriospinal axons with glial-derived neurotrophic factor16,17 delivered via spatially and temporally controlled release from biomaterial depots18,19, placed sequentially after SCI. We show in both mice and rats that providing these three mechanisms in combination, but not individually, stimulated robust propriospinal axon regrowth through astrocyte scar borders and across lesion cores of non-neural tissue that was over 100-fold greater than controls. Stimulated, supported and chemoattracted propriospinal axons regrew a full spinal segment beyond lesion centres, passed well into spared neural tissue, formed terminal-like contacts exhibiting synaptic markers and conveyed a significant return of electrophysiological conduction capacity across lesions. Thus, overcoming the failure of axon regrowth across anatomically complete SCI lesions after maturity required the combined sequential reinstatement of several developmentally essential mechanisms that facilitate axon growth. These findings identify a mechanism-based biological repair strategy for complete SCI lesions that could be suitable to use with rehabilitation models designed to augment the functional recovery of remodelling circuits.}, } @article {pmid30158697, year = {2018}, author = {Kato, HE and Kim, YS and Paggi, JM and Evans, KE and Allen, WE and Richardson, C and Inoue, K and Ito, S and Ramakrishnan, C and Fenno, LE and Yamashita, K and Hilger, D and Lee, SY and Berndt, A and Shen, K and Kandori, H and Dror, RO and Kobilka, BK and Deisseroth, K}, title = {Structural mechanisms of selectivity and gating in anion channelrhodopsins.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {349-354}, doi = {10.1038/s41586-018-0504-5}, pmid = {30158697}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; R01 MH075957/MH/NIMH NIH HHS/United States ; }, abstract = {Both designed and natural anion-conducting channelrhodopsins (dACRs and nACRs, respectively) have been widely applied in optogenetics (enabling selective inhibition of target-cell activity during animal behaviour studies), but each class exhibits performance limitations, underscoring trade-offs in channel structure-function relationships. Therefore, molecular and structural insights into dACRs and nACRs will be critical not only for understanding the fundamental mechanisms of these light-gated anion channels, but also to create next-generation optogenetic tools. Here we report crystal structures of the dACR iC++, along with spectroscopic, electrophysiological and computational analyses that provide unexpected insights into pH dependence, substrate recognition, channel gating and ion selectivity of both dACRs and nACRs. These results enabled us to create an anion-conducting channelrhodopsin integrating the key features of large photocurrent and fast kinetics alongside exclusive anion selectivity.}, } @article {pmid30158696, year = {2018}, author = {Kim, YS and Kato, HE and Yamashita, K and Ito, S and Inoue, K and Ramakrishnan, C and Fenno, LE and Evans, KE and Paggi, JM and Dror, RO and Kandori, H and Kobilka, BK and Deisseroth, K}, title = {Crystal structure of the natural anion-conducting channelrhodopsin GtACR1.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {343-348}, doi = {10.1038/s41586-018-0511-6}, pmid = {30158696}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; R01 MH075957/MH/NIMH NIH HHS/United States ; }, abstract = {The naturally occurring channelrhodopsin variant anion channelrhodopsin-1 (ACR1), discovered in the cryptophyte algae Guillardia theta, exhibits large light-gated anion conductance and high anion selectivity when expressed in heterologous settings, properties that support its use as an optogenetic tool to inhibit neuronal firing with light. However, molecular insight into ACR1 is lacking owing to the absence of structural information underlying light-gated anion conductance. Here we present the crystal structure of G. theta ACR1 at 2.9 Å resolution. The structure reveals unusual architectural features that span the extracellular domain, retinal-binding pocket, Schiff-base region, and anion-conduction pathway. Together with electrophysiological and spectroscopic analyses, these findings reveal the fundamental molecular basis of naturally occurring light-gated anion conductance, and provide a framework for designing the next generation of optogenetic tools.}, } @article {pmid30158687, year = {2018}, author = {}, title = {GPS for navigating healthcare.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1197}, doi = {10.1038/s41588-018-0230-9}, pmid = {30158687}, issn = {1546-1718}, } @article {pmid30158686, year = {2018}, author = {Tsai, A and Crocker, J}, title = {Visualizing long-range enhancer-promoter interaction.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1205-1206}, doi = {10.1038/s41588-018-0198-5}, pmid = {30158686}, issn = {1546-1718}, } @article {pmid30158685, year = {2018}, author = {McFerrin, LG and Zager, M and Zhang, J and Krenn, G and McDermott, R and Horse-Grant, D and Silgard, E and Colevas, K and Shannon, P and Bolouri, H and Holland, EC}, title = {Analysis and visualization of linked molecular and clinical cancer data by using Oncoscape.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1203-1204}, doi = {10.1038/s41588-018-0208-7}, pmid = {30158685}, issn = {1546-1718}, } @article {pmid30158684, year = {2018}, author = {Turnbull, C and Sud, A and Houlston, RS}, title = {Cancer genetics, precision prevention and a call to action.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1212-1218}, doi = {10.1038/s41588-018-0202-0}, pmid = {30158684}, issn = {1546-1718}, abstract = {More than 15 years have passed since the identification, through linkage, of 'first-wave' susceptibility genes for common cancers (BRCA1, BRCA2, MLH1 and MSH2). These genes have strong frequency-penetrance profiles, such that the associated clinical utility probably remains relevant regardless of the context of ascertainment. 'Second-wave' genes, not tractable by linkage, were subsequently identified by mutation screening of candidate genes (PALB2, ATM, CHEK2, BRIP1, RAD51C and RAD51D). Their innately weaker frequency-penetrance profiles have rendered delineation of cancer associations, risks and variant pathogenicity challenging, thereby compromising their clinical application. Early germline exome-sequencing endeavors for common cancers did not yield the long-anticipated slew of 'next-wave' genes but instead implied a highly polygenic genomic architecture requiring much larger experiments to make any substantive inroads into gene discovery. As such, the 'genetic economics' of frequency penetrance clearly indicates that focused identification of carriers of first-wave-gene mutations is most impactful for cancer control. With screening, prevention and early detection at the forefront of the cancer management agenda, we propose that the time is nigh for the initiation of national population-testing programs to identify carriers of first-wave gene mutation carriers. To fully deliver a precision prevention program, long-term, large-scale mutation studies that capture longitudinal clinical data and serial biosamples are required.}, } @article {pmid30158683, year = {2018}, author = {Krause, K and Turck, F}, title = {Plant H3K27me3 has finally found its readers.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1206-1208}, doi = {10.1038/s41588-018-0201-1}, pmid = {30158683}, issn = {1546-1718}, } @article {pmid30158682, year = {2018}, author = {Jubb, HC and Saini, HK and Verdonk, ML and Forbes, SA}, title = {COSMIC-3D provides structural perspectives on cancer genetics for drug discovery.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1200-1202}, pmid = {30158682}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; }, } @article {pmid30158681, year = {2018}, author = {Schork, AJ and Schork, MA and Schork, NJ}, title = {Genetic risks and clinical rewards.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1210-1211}, doi = {10.1038/s41588-018-0213-x}, pmid = {30158681}, issn = {1546-1718}, support = {U24 AG051129/AG/NIA NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; }, } @article {pmid30158680, year = {2018}, author = {Shah, SP}, title = {Copy number signatures in ovarian cancer.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1208-1209}, doi = {10.1038/s41588-018-0212-y}, pmid = {30158680}, issn = {1546-1718}, } @article {pmid30158623, year = {2018}, author = {Cernansky, R}, title = {How to plant a trillion trees.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {542-544}, doi = {10.1038/d41586-018-06031-x}, pmid = {30158623}, issn = {1476-4687}, mesh = {Africa ; Animals ; Biodiversity ; Ecology/economics/methods/standards/trends ; *Ecosystem ; Environmental Restoration and Remediation/economics/*methods/standards/*trends ; Forestry/economics/methods/*standards/*trends ; Forests ; Goals ; History, 20th Century ; Latin America ; Philippines ; Species Specificity ; *Trees/classification/growth & development ; }, } @article {pmid30158622, year = {2018}, author = {}, title = {Foreign research funds, Australia's science minister and gene editing in Japan.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {532-533}, doi = {10.1038/d41586-018-06041-9}, pmid = {30158622}, issn = {1476-4687}, } @article {pmid30158621, year = {2018}, author = {Polka, JK and Kiley, R and Konforti, B and Stern, B and Vale, RD}, title = {Publish peer reviews.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {545-547}, doi = {10.1038/d41586-018-06032-w}, pmid = {30158621}, issn = {1476-4687}, mesh = {*Access to Information ; Biological Science Disciplines ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Peer Review, Research/*methods/standards ; *Periodicals as Topic/history ; }, } @article {pmid30158620, year = {2018}, author = {}, title = {Feeling the pull of gravity.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {527}, doi = {10.1038/d41586-018-06044-6}, pmid = {30158620}, issn = {1476-4687}, } @article {pmid30158619, year = {2018}, author = {Sarabipour, S}, title = {Preprints are good for science and good for the public.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {553}, doi = {10.1038/d41586-018-06054-4}, pmid = {30158619}, issn = {1476-4687}, mesh = {*Publishing ; *Science ; }, } @article {pmid30158618, year = {2018}, author = {Balistreri, E and Kaffine, D and Yonezawa, H}, title = {Consumption rebound could undermine border carbon-adjustment charges.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {553}, doi = {10.1038/d41586-018-06056-2}, pmid = {30158618}, issn = {1476-4687}, mesh = {*Carbon ; Climate ; Environmental Policy ; *Greenhouse Effect ; }, } @article {pmid30158617, year = {2018}, author = {Fraser, J and Polka, J}, title = {Together scientists and journalists can spot poor preprints.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {553}, doi = {10.1038/d41586-018-06053-5}, pmid = {30158617}, issn = {1476-4687}, mesh = {*Information Dissemination ; *Mass Media ; }, } @article {pmid30158616, year = {2018}, author = {Tennant, J and Gatto, L and Logan, C}, title = {Preprints help journalism, not hinder it.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {553}, doi = {10.1038/d41586-018-06055-3}, pmid = {30158616}, issn = {1476-4687}, } @article {pmid30158615, year = {2018}, author = {}, title = {Opening up peer review.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {527}, doi = {10.1038/d41586-018-06045-5}, pmid = {30158615}, issn = {1476-4687}, mesh = {*Peer Review ; *Publishing ; }, } @article {pmid30158613, year = {2018}, author = {Rickard, D}, title = {A double-edged retirement honour.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {553}, doi = {10.1038/d41586-018-06058-0}, pmid = {30158613}, issn = {1476-4687}, mesh = {*Life ; *Retirement ; }, } @article {pmid30158612, year = {2018}, author = {Schlamminger, S}, title = {Gravity measured with record precision.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {562-563}, doi = {10.1038/d41586-018-06028-6}, pmid = {30158612}, issn = {1476-4687}, } @article {pmid30158611, year = {2018}, author = {Beroza, GC}, title = {Machine learning improves forecasts of aftershock locations.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {556-557}, doi = {10.1038/d41586-018-06030-y}, pmid = {30158611}, issn = {1476-4687}, mesh = {Algorithms ; *Deep Learning ; *Earthquakes ; Forecasting ; Machine Learning ; }, } @article {pmid30158610, year = {2018}, author = {Kinzler, KD and Shutts, K}, title = {Ways to promote and foster collaborative research in your lab.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {673}, doi = {10.1038/d41586-018-06037-5}, pmid = {30158610}, issn = {1476-4687}, } @article {pmid30158607, year = {2018}, author = {Li, Q and Xue, C and Liu, JP and Wu, JF and Yang, SQ and Shao, CG and Quan, LD and Tan, WH and Tu, LC and Liu, Q and Xu, H and Liu, LX and Wang, QL and Hu, ZK and Zhou, ZB and Luo, PS and Wu, SC and Milyukov, V and Luo, J}, title = {Measurements of the gravitational constant using two independent methods.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {582-588}, doi = {10.1038/s41586-018-0431-5}, pmid = {30158607}, issn = {1476-4687}, abstract = {The Newtonian gravitational constant, G, is one of the most fundamental constants of nature, but we still do not have an accurate value for it. Despite two centuries of experimental effort, the value of G remains the least precisely known of the fundamental constants. A discrepancy of up to 0.05 per cent in recent determinations of G suggests that there may be undiscovered systematic errors in the various existing methods. One way to resolve this issue is to measure G using a number of methods that are unlikely to involve the same systematic effects. Here we report two independent determinations of G using torsion pendulum experiments with the time-of-swing method and the angular-acceleration-feedback method. We obtain G values of 6.674184 × 10-11 and 6.674484 × 10-11 cubic metres per kilogram per second squared, with relative standard uncertainties of 11.64 and 11.61 parts per million, respectively. These values have the smallest uncertainties reported until now, and both agree with the latest recommended value within two standard deviations.}, } @article {pmid30158606, year = {2018}, author = {DeVries, PMR and Viégas, F and Wattenberg, M and Meade, BJ}, title = {Deep learning of aftershock patterns following large earthquakes.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {632-634}, doi = {10.1038/s41586-018-0438-y}, pmid = {30158606}, issn = {1476-4687}, abstract = {Aftershocks are a response to changes in stress generated by large earthquakes and represent the most common observations of the triggering of earthquakes. The maximum magnitude of aftershocks and their temporal decay are well described by empirical laws (such as Bath's law1 and Omori's law2), but explaining and forecasting the spatial distribution of aftershocks is more difficult. Coulomb failure stress change3 is perhaps the most widely used criterion to explain the spatial distributions of aftershocks4-8, but its applicability has been disputed9-11. Here we use a deep-learning approach to identify a static-stress-based criterion that forecasts aftershock locations without prior assumptions about fault orientation. We show that a neural network trained on more than 131,000 mainshock-aftershock pairs can predict the locations of aftershocks in an independent test dataset of more than 30,000 mainshock-aftershock pairs more accurately (area under curve of 0.849) than can classic Coulomb failure stress change (area under curve of 0.583). We find that the learned aftershock pattern is physically interpretable: the maximum change in shear stress, the von Mises yield criterion (a scaled version of the second invariant of the deviatoric stress-change tensor) and the sum of the absolute values of the independent components of the stress-change tensor each explain more than 98 per cent of the variance in the neural-network prediction. This machine-learning-driven insight provides improved forecasts of aftershock locations and identifies physical quantities that may control earthquake triggering during the most active part of the seismic cycle.}, } @article {pmid30158605, year = {2018}, author = {Tadaki, K and Iono, D and Yun, MS and Aretxaga, I and Hatsukade, B and Hughes, DH and Ikarashi, S and Izumi, T and Kawabe, R and Kohno, K and Lee, M and Matsuda, Y and Nakanishi, K and Saito, T and Tamura, Y and Ueda, J and Umehata, H and Wilson, GW and Michiyama, T and Ando, M and Kamieneski, P}, title = {The gravitationally unstable gas disk of a starburst galaxy 12 billion years ago.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {613-616}, doi = {10.1038/s41586-018-0443-1}, pmid = {30158605}, issn = {1476-4687}, abstract = {Galaxies in the early Universe that are bright at submillimetre wavelengths (submillimetre-bright galaxies) are forming stars at a rate roughly 1,000 times higher than the Milky Way. A large fraction of the new stars form in the central kiloparsec of the galaxy1-3, a region that is comparable in size to the massive, quiescent galaxies found at the peak of cosmic star-formation history4 and the cores of present-day giant elliptical galaxies. The physical and kinematic properties inside these compact starburst cores are poorly understood because probing them at relevant spatial scales requires extremely high angular resolution. Here we report observations with a linear resolution of 550 parsecs of gas and dust in an unlensed, submillimetre-bright galaxy at a redshift of z = 4.3, when the Universe was less than two billion years old. We resolve the spatial and kinematic structure of the molecular gas inside the heavily dust-obscured core and show that the underlying gas disk is clumpy and rotationally supported (that is, its rotation velocity is larger than the velocity dispersion). Our analysis of the molecular gas mass per unit area suggests that the starburst disk is gravitationally unstable, which implies that the self-gravity of the gas is stronger than the differential rotation of the disk and the internal pressure due to stellar-radiation feedback. As a result of the gravitational instability in the disk, the molecular gas would be consumed by star formation on a timescale of 100 million years, which is comparable to gas depletion times in merging starburst galaxies5.}, } @article {pmid30158604, year = {2018}, author = {Cheben, P and Halir, R and Schmid, JH and Atwater, HA and Smith, DR}, title = {Subwavelength integrated photonics.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {565-572}, doi = {10.1038/s41586-018-0421-7}, pmid = {30158604}, issn = {1476-4687}, abstract = {In the late nineteenth century, Heinrich Hertz demonstrated that the electromagnetic properties of materials are intimately related to their structure at the subwavelength scale by using wire grids with centimetre spacing to manipulate metre-long radio waves. More recently, the availability of nanometre-scale fabrication techniques has inspired scientists to investigate subwavelength-structured metamaterials with engineered optical properties at much shorter wavelengths, in the infrared and visible regions of the spectrum. Here we review how optical metamaterials are expected to enhance the performance of the next generation of integrated photonic devices, and explore some of the challenges encountered in the transition from concept demonstration to viable technology.}, } @article {pmid30158603, year = {2018}, author = {Humphrey, V and Zscheischler, J and Ciais, P and Gudmundsson, L and Sitch, S and Seneviratne, SI}, title = {Sensitivity of atmospheric CO2 growth rate to observed changes in terrestrial water storage.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {628-631}, doi = {10.1038/s41586-018-0424-4}, pmid = {30158603}, issn = {1476-4687}, abstract = {Land ecosystems absorb on average 30 per cent of anthropogenic carbon dioxide (CO2) emissions, thereby slowing the increase of CO2 concentration in the atmosphere1. Year-to-year variations in the atmospheric CO2 growth rate are mostly due to fluctuating carbon uptake by land ecosystems1. The sensitivity of these fluctuations to changes in tropical temperature has been well documented2-6, but identifying the role of global water availability has proved to be elusive. So far, the only usable proxies for water availability have been time-lagged precipitation anomalies and drought indices3-5, owing to a lack of direct observations. Here, we use recent observations of terrestrial water storage changes derived from satellite gravimetry7 to investigate terrestrial water effects on carbon cycle variability at global to regional scales. We show that the CO2 growth rate is strongly sensitive to observed changes in terrestrial water storage, drier years being associated with faster atmospheric CO2 growth. We demonstrate that this global relationship is independent of known temperature effects and is underestimated in current carbon cycle models. Our results indicate that interannual fluctuations in terrestrial water storage strongly affect the terrestrial carbon sink and highlight the importance of the interactions between the water and carbon cycles.}, } @article {pmid30158602, year = {2018}, author = {Pierson, TC and Diamond, MS}, title = {The emergence of Zika virus and its new clinical syndromes.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {573-581}, doi = {10.1038/s41586-018-0446-y}, pmid = {30158602}, issn = {1476-4687}, support = {R01 AI073755/AI/NIAID NIH HHS/United States ; R01 AI104972/AI/NIAID NIH HHS/United States ; U19 AI083019/AI/NIAID NIH HHS/United States ; R01 HD091218/HD/NICHD NIH HHS/United States ; }, abstract = {Zika virus (ZIKV) is a mosquito-transmitted flavivirus that has emerged as a global health threat because of its potential to generate explosive epidemics and ability to cause congenital disease in the context of infection during pregnancy. Whereas much is known about the biology of related flaviviruses, the unique features of ZIKV pathogenesis, including infection of the fetus, persistence in immune-privileged sites and sexual transmission, have presented new challenges. The rapid development of cell culture and animal models has facilitated a new appreciation of ZIKV biology. This knowledge has created opportunities for the development of countermeasures, including multiple ZIKV vaccine candidates, which are advancing through clinical trials. Here we describe the recent advances that have led to a new understanding of the causes and consequences of the ZIKV epidemic.}, } @article {pmid30158171, year = {2018}, author = {Mizotani, Y and Suzuki, M and Hotta, K and Watanabe, H and Shiba, K and Inaba, K and Tashiro, E and Oka, K and Imoto, M}, title = {14-3-3εa directs the pulsatile transport of basal factors toward the apical domain for lumen growth in tubulogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8873-E8881}, pmid = {30158171}, issn = {1091-6490}, mesh = {14-3-3 Proteins/genetics/*physiology ; Animals ; Benzaldehydes/pharmacology ; Ciona intestinalis/*embryology/genetics ; Cytoplasm/metabolism ; Cytoskeletal Proteins/genetics/metabolism ; Endothelial Cells/*physiology ; Larva/growth & development ; Membrane Proteins/genetics/metabolism ; Microfilament Proteins/genetics/metabolism ; Morphogenesis/drug effects/genetics/*physiology ; Morpholinos/genetics ; Myosin Type II/metabolism ; Notochord/embryology ; }, abstract = {The Ciona notochord has emerged as a simple and tractable in vivo model for tubulogenesis. Here, using a chemical genetics approach, we identified UTKO1 as a selective small molecule inhibitor of notochord tubulogenesis. We identified 14-3-3εa protein as a direct binding partner of UTKO1 and showed that 14-3-3εa knockdown leads to failure of notochord tubulogenesis. We found that UTKO1 prevents 14-3-3εa from interacting with ezrin/radixin/moesin (ERM), which is required for notochord tubulogenesis, suggesting that interactions between 14-3-3εa and ERM play a key role in regulating the early steps of tubulogenesis. Using live imaging, we found that, as lumens begin to open between neighboring cells, 14-3-3εa and ERM are highly colocalized at the basal cortex where they undergo cycles of accumulation and disappearance. Interestingly, the disappearance of 14-3-3εa and ERM during each cycle is tightly correlated with a transient flow of 14-3-3εa, ERM, myosin II, and other cytoplasmic elements from the basal surface toward the lumen-facing apical domain, which is often accompanied by visible changes in lumen architecture. Both pulsatile flow and lumen formation are abolished in larvae treated with UTKO1, in larvae depleted of either 14-3-3εa or ERM, or in larvae expressing a truncated form of 14-3-3εa that lacks the ability to interact with ERM. These results suggest that 14-3-3εa and ERM interact at the basal cortex to direct pulsatile basal accumulation and basal-apical transport of factors that are essential for lumen formation. We propose that similar mechanisms may underlie or may contribute to lumen formation in tubulogenesis in other systems.}, } @article {pmid30158170, year = {2018}, author = {Ritvo, PG and Saadawi, A and Barennes, P and Quiniou, V and Chaara, W and El Soufi, K and Bonnet, B and Six, A and Shugay, M and Mariotti-Ferrandiz, E and Klatzmann, D}, title = {High-resolution repertoire analysis reveals a major bystander activation of Tfh and Tfr cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9604-9609}, pmid = {30158170}, issn = {1091-6490}, mesh = {Animals ; Antibody Formation/immunology ; Antigens/immunology ; B-Lymphocytes/immunology ; Female ; Gene Expression Profiling/methods ; Germinal Center/cytology/*immunology/metabolism ; High-Throughput Nucleotide Sequencing ; Lymphocyte Activation/*immunology ; Male ; Mice, Inbred NOD ; Models, Animal ; Receptors, Antigen, T-Cell, alpha-beta/*genetics/metabolism ; Sequence Analysis, DNA ; T-Lymphocytes, Helper-Inducer/*immunology/metabolism ; T-Lymphocytes, Regulatory/*immunology/metabolism ; }, abstract = {T follicular helper (Tfh) and regulatory (Tfr) cells are terminally differentiated cells found in germinal centers (GCs), specialized secondary lymphoid organ structures dedicated to antibody production. As such, follicular T (Tfol) cells are supposed to be specific for immunizing antigens, which has been reported for Tfh cells but is debated for Tfr cells. Here, we used high-throughput T cell receptor (TCR) sequencing to analyze the repertoires of Tfh and Tfr cells, at homeostasis and after immunization with self- or foreign antigens. We observed that, whatever the conditions, Tfh and Tfr cell repertoires are less diverse than those of effector T cells and Treg cells of the same tissues; surprisingly, these repertoires still represent thousands of different sequences, even after immunization with a single antigen that induces a 10-fold increase in Tfol cell numbers. Thorough analysis of the sharing and network of TCR sequences revealed that a specific response to the immunizing antigen can only, but hardly, be detected in Tfh cells immunized with a foreign antigen and Tfr cells immunized with a self-antigen. These antigen-specific responses are obscured by a global stimulation of Tfh and Tfr cells that appears to be antigen-independent. Altogether, our results suggest a major bystander Tfol cell activation during the immune response in the GCs.}, } @article {pmid30158169, year = {2018}, author = {Berdanier, W and Kolodrubetz, M and Parameswaran, SA and Vasseur, R}, title = {Floquet quantum criticality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9491-9496}, pmid = {30158169}, issn = {1091-6490}, abstract = {We study transitions between distinct phases of one-dimensional periodically driven (Floquet) systems. We argue that these are generically controlled by infinite-randomness fixed points of a strong-disorder renormalization group procedure. Working in the fermionic representation of the prototypical Floquet Ising chain, we leverage infinite randomness physics to provide a simple description of Floquet (multi)criticality in terms of a distinct type of domain wall associated with time translational symmetry-breaking and the formation of "Floquet time crystals." We validate our analysis via numerical simulations of free-fermion models sufficient to capture the critical physics.}, } @article {pmid30158168, year = {2018}, author = {Li, L and Li, JC and Yang, H and Zhang, X and Liu, LL and Li, Y and Zeng, TT and Zhu, YH and Li, XD and Li, Y and Xie, D and Fu, L and Guan, XY}, title = {Expansion of cancer stem cell pool initiates lung cancer recurrence before angiogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8948-E8957}, pmid = {30158168}, issn = {1091-6490}, mesh = {AC133 Antigen/metabolism ; Animals ; Carcinoma, Non-Small-Cell Lung/blood/*pathology ; Cell Line, Tumor ; Cell Proliferation ; Chemokine CXCL1/antagonists & inhibitors/metabolism ; Female ; Humans ; Insulin-Like Growth Factor I/analysis/antagonists & inhibitors/*metabolism ; Lung Neoplasms/blood/*pathology ; Mice ; Mice, Nude ; Neoplasm Recurrence, Local/blood/*pathology ; Neoplastic Stem Cells/*pathology ; Neovascularization, Pathologic/blood/*pathology ; Phosphatidylinositol 3-Kinases/metabolism ; Placenta Growth Factor/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction ; Xenograft Model Antitumor Assays ; beta Catenin/metabolism ; }, abstract = {Angiogenesis is essential in the early stage of solid tumor recurrence, but how a suspensive tumor is reactivated before angiogenesis is mostly unknown. Herein, we stumble across an interesting phenomenon that s.c. xenografting human lung cancer tissues can awaken the s.c. suspensive tumor in nude mice. We further found that a high level of insulin-like growth factor 1 (IGF1) was mainly responsible for triggering the transition from suspensive tumor to progressive tumor in this model. The s.c. suspensive tumor is characterized with growth arrest, avascularity, and a steady-state level of proliferating and apoptotic cells. Intriguingly, CD133+ lung cancer stem cells (LCSCs) are highly enriched in suspensive tumor compared with progressive tumor. Mechanistically, high IGF1 initiates LCSCs self-renewal from asymmetry to symmetry via the activation of a PI3K/Akt/β-catenin axis. Next, the expansion of LCSC pool promotes angiogenesis by increasing the production of CXCL1 and PlGF in CD133+ LCSCs, which results in lung cancer recurrence. Clinically, a high level of serum IGF1 in lung cancer patients after orthotopic lung cancer resection as an unfavorable factor is strongly correlated with the high rate of recurrence and indicates an adverse progression-free survival. Vice versa, blocking IGF1 or CXCL1/PlGF with neutralizing antibodies can prevent the reactivation of a suspensive tumor induced by IGF1 stimulation in the mouse model. Collectively, the expansion of LCSC pool before angiogenesis induced by IGF1 is a key checkpoint during the initiation of cancer relapse, and targeting serum IGF1 may be a promising treatment for preventing recurrence in lung cancer patients.}, } @article {pmid30158167, year = {2018}, author = {Moser, D and Lenzner, B and Weigelt, P and Dawson, W and Kreft, H and Pergl, J and Pyšek, P and van Kleunen, M and Winter, M and Capinha, C and Cassey, P and Dullinger, S and Economo, EP and García-Díaz, P and Guénard, B and Hofhansl, F and Mang, T and Seebens, H and Essl, F}, title = {Remoteness promotes biological invasions on islands worldwide.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9270-9275}, pmid = {30158167}, issn = {1091-6490}, mesh = {*Introduced Species ; *Islands ; *Models, Biological ; *Tropical Climate ; }, abstract = {One of the best-known general patterns in island biogeography is the species-isolation relationship (SIR), a decrease in the number of native species with increasing island isolation that is linked to lower rates of natural dispersal and colonization on remote oceanic islands. However, during recent centuries, the anthropogenic introduction of alien species has increasingly gained importance and altered the composition and richness of island species pools. We analyzed a large dataset for alien and native plants, ants, reptiles, mammals, and birds on 257 (sub) tropical islands, and showed that, except for birds, the number of naturalized alien species increases with isolation for all taxa, a pattern that is opposite to the negative SIR of native species. We argue that the reversal of the SIR for alien species is driven by an increase in island invasibility due to reduced diversity and increased ecological naiveté of native biota on the more remote islands.}, } @article {pmid30157961, year = {2018}, author = {Bantawa, K and Rai, K and Subba Limbu, D and Khanal, H}, title = {Food-borne bacterial pathogens in marketed raw meat of Dharan, eastern Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {618}, pmid = {30157961}, issn = {1756-0500}, support = {20//University Grants Commission- Nepal/ ; }, mesh = {Animals ; Colony Count, Microbial ; Escherichia coli/*isolation & purification ; *Food Contamination ; Food Microbiology ; Meat/*microbiology ; Nepal ; Staphylococcus aureus/*isolation & purification ; }, abstract = {OBJECTIVES: This study aims to assess the bacteriological quality of marketed raw meat with a special emphasis on isolation of Escherichia coli, Salmonella spp., Shigella spp., Vibrio spp., Pseudomonas aeruginosa and Staphylococcus aureus in raw meat marketed in Dharan. Altogether 50 meat samples were collected from local markets of Dharan and transported to the microbiology laboratory at 4 °C. The meat samples were homogenized in a sterile glass homogenizer and the possible pathogens were isolated and identified by conventional microbiological techniques.

RESULTS: The mean total viable count values were found having a mean count of 8.22 ± 0.14, 8.29 ± 0.17, 7.87 ± 0.18 and 7.92 ± 0.19 in terms of log10 CFU/g ± Standard Error for chicken, pork, buffalo, and goat meat respectively. Coliforms were found in 84% samples, S. aureus was found in 68% samples, Salmonella spp. in 34% samples, Shigella spp. in 6% samples, Vibrio spp. in only 3 samples and P. aeruginosa was isolated from 40% sample. Higher microbial load and presence of intestinal commensals E. coli, Salmonella spp., Shigella spp., Vibrio spp indicates that meat might be contaminated by the visceral content and consumers are at risk of getting a foodborne disease when eaten raw.}, } @article {pmid30157960, year = {2018}, author = {Nivesvivat, T and Piyaraj, P and Thunyaharn, S and Watanaveeradej, V and Suwanpakdee, D}, title = {Clinical epidemiology, risk factors and treatment outcomes of extended-spectrum beta-lactamase producing Enterobacteriaceae bacteremia among children in a Tertiary Care Hospital, Bangkok, Thailand.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {624}, pmid = {30157960}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteremia/*drug therapy ; Child ; Child, Preschool ; Enterobacteriaceae ; Enterobacteriaceae Infections/*drug therapy/enzymology ; Escherichia coli/isolation & purification ; Humans ; Infant ; Infant, Newborn ; Klebsiella/isolation & purification ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; Thailand ; Treatment Outcome ; beta-Lactamases/*metabolism ; }, abstract = {OBJECTIVE: Extended-spectrum beta-lactamase (ESBL) producing Enterobacteriaceae infection is an emerging problem in paediatric populations leading to increased mortality. The purpose of this study was to determine the prevalence, risk factors and clinical outcomes of ESBL-producing Enterobacteriaceae in paediatric blood stream infections (BSIs). A retrospective review of paediatric patients diagnosed with Enterobacteriaceae bacteremia was performed at Phramongkutklao Hospital from 2010 to 2017.

RESULTS: Among 97 non-duplicated blood isolates, the prevalence of ESBL-producing Enterobacteriaceae was 53.6% (28.9% Escherichia coli and 25.8% Klebsiella spp. isolates). The study indicated that the prevalence of ESBL infection was higher among patients with chronic illness, especially hematologic malignancies, than among patients without underlying disease (P = 0.01). No differences were observed in the prior use of any antibiotics, the use of extended-spectrum cephalosporin, neutropaenia or the presence of an indwelling central venous catheter. Mortality in the ESBL group was significantly higher than that in the non-ESBL group, with observed mortalities of 38.9% and 13.3%, respectively (P < 0.05). In conclusion, BSIs with ESBL-producing Enterobacteriaceae tended to increase infection rates and impact survival rates among paediatric patients.}, } @article {pmid30157953, year = {2018}, author = {Shanahan, ER and Shah, A and Koloski, N and Walker, MM and Talley, NJ and Morrison, M and Holtmann, GJ}, title = {Influence of cigarette smoking on the human duodenal mucosa-associated microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {150}, pmid = {30157953}, issn = {2049-2618}, abstract = {BACKGROUND: Cigarette smoking is a known risk factor in a number of gastrointestinal (GI) diseases in which the microbiota is implicated, including duodenal ulcer and Crohn's disease. Smoking has the potential to alter the microbiota; however, to date, the impact of smoking on the mucosa-associated microbiota (MAM), and particularly that of the upper GI tract, remains very poorly characterised. Thus, we investigated the impact of smoking on the upper small intestinal MAM. A total of 102 patients undergoing upper GI endoscopy for the assessment of GI symptoms, iron deficiency, or Crohn's disease, but without identifiable lesions in the duodenum, were recruited. Smoking status was determined during clinical assessment and patients classified as current (n = 21), previous smokers (n = 40), or having never smoked (n = 41). The duodenal (D2) MAM was profiled via 16S rRNA gene amplicon sequencing.

RESULTS: Smoking, both current and previous, is associated with significantly reduced bacterial diversity in the upper small intestinal mucosa, as compared to patients who had never smoked. This was accompanied by higher relative abundance of Firmicutes, specifically Streptococcus and Veillonella spp. The relative abundance of the genus Rothia was also observed to be greater in current smokers; while in contrast, levels of Prevotella and Neisseria were lower. The MAM profiles and diversity of previous smokers were observed to be intermediate between current and never smokers. Smoking did not impact the total density of bacteria present on the mucosa.

CONCLUSIONS: These data indicate the duodenal MAM of current smokers is characterised by reduced bacterial diversity, which is partially but not completely restored in previous smokers. While the precise mechanisms remain to be elucidated, these microbiota changes may in some part explain the adverse effects of smoking on mucosa-associated diseases of the GI tract. Smoking status requires consideration when interpreting MAM data.}, } @article {pmid30157951, year = {2018}, author = {Abay, M and Tuke, G and Zewdie, E and Abraha, TH and Grum, T and Brhane, E}, title = {Breast self-examination practice and associated factors among women aged 20-70 years attending public health institutions of Adwa town, North Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {622}, pmid = {30157951}, issn = {1756-0500}, mesh = {Adult ; Aged ; Breast Self-Examination/*statistics & numerical data ; Cross-Sectional Studies ; Ethiopia ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Public Health ; Young Adult ; }, abstract = {OBJECTIVE: Breast cancer is the leading cause of cancer mortality worldwide. The incidence of breast has been increasing in most regions of the world. Regular breast self-examination is one of the most cost-effective methods for early detection of breast cancer in asymptomatic women. Despite this fact, breast self-examination practice remains low in Ethiopia. Therefore, the aim of this study is to assess breast self-examination practice and associated factors among women aged 20-70 years attending public health institutions of Adwa town, North Ethiopia.

RESULTS: From the total study participants, only 26 (6.5%) of them had ever practice breast self-examination, and only 25 (6.25%) of them practice breast self-examination regularly. Being a government employee (AOR = 0.22, 95% CI = 0.071-0.683), having good perceived confidence to do breast self-examination (AOR = 5.32, 95% CI = 1.89-14.95) and having perceived good susceptibility to develop breast cancer (AOR = 3.79, 95% CI = 1.74-9.74) were the factors significantly associated with breast self-examination. Breast self-examination practice among the study participants was low. Therefore, informing every woman is susceptible to breast cancer, improving the confidence of women is recommended to increase breast self-examination practice.}, } @article {pmid30157946, year = {2018}, author = {Björkhem-Bergman, L and Torefalk, E and Ekström, L and Bergman, P}, title = {Vitamin D binding protein is not affected by high-dose vitamin D supplementation: a post hoc analysis of a randomised, placebo-controlled study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {619}, pmid = {30157946}, issn = {1756-0500}, support = {CAN 2015/249//Cancerfonden/ ; CAN 2017/233//Cancerfonden/ ; ALF//Stockholms Läns Landsting/ ; 20130317//Stockholms Läns Landsting/ ; ALF 20160036//Stockholms Läns Landsting/ ; VR//Vetenskapsrådet/ ; 2013-1047//Vetenskapsrådet/ ; }, mesh = {Carrier State ; Double-Blind Method ; Humans ; Methicillin-Resistant Staphylococcus aureus ; Vitamin D/*pharmacology ; Vitamin D Deficiency ; Vitamin D-Binding Protein ; Vitamins/*pharmacology ; }, abstract = {OBJECTIVES: Vitamin D binding protein (VDBP) is the main transporter of 25-hydroxyvitamin D3 (25-OHD) in the circulation. The aim of this study was to investigate if VDBP is affected by high dose vitamin D supplementation and if VDBP-levels correlate with free 25-OHD. Correlation between free 25-OHD measured with ELISA and total 25-OHD in the circulation was also analysed. Plasma samples from a randomized, controlled trial in which persistent MRSA-carriers were randomized to treatment with vitamin D, 4000 IE/day, (n = 27) or placebo (n = 32) for 12 months were used. Plasma from baseline and after 6 months of treatment were analysed for VDBP, 25-OHD and free 25-OHD.

RESULTS: VDBP levels were not affected by vitamin D treatment, although the 25-OHD levels increased significantly in the vitamin D treated subjects. There was a strong correlation between 25-OHD and free 25-OHD (r2 = 0.68, p < 0.0001), while there was no correlation between VDBP and free 25-OHD. Thus, our data shows that VDBP are not affected by vitamin D supplementation and the levels of VDBP are not associated with the free fraction of 25-OHD. Since there was a strong correlation between free 25-OHD and total 25-OHD it appears to be sufficient to measure only total 25-OHD. Trial registration http://www.clinicaltrials.gov ; NCT02178488. Date of registration: June 30, 2014; Date of enrolment of the first participant: Dec 1, 2014.}, } @article {pmid30157944, year = {2018}, author = {Mohamed, NS and Siddig, EE and Mohamed, MA and Alzein, BA and Osman, HHS and Tanyous, EE and Elamin, BK and Edris, AMM}, title = {Enteroparasitosis infections among renal transplant recipients in Khartoum state, Sudan 2012-2013.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {621}, pmid = {30157944}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Child ; Feces ; Female ; Humans ; Intestinal Diseases, Parasitic/epidemiology/*etiology ; Kidney Transplantation/*adverse effects ; Male ; Middle Aged ; Parasites ; Prevalence ; Sudan/epidemiology ; Young Adult ; }, abstract = {OBJECTIVES: Renal transplantation procedure markedly increased over the past few decades. The risk of harboring parasitic diseases may affect transplant recipients during life expectancy. We aimed in this study to determine the enteroparasitosis frequency among renal transplant recipients in Khartoum state, Sudan. A case-control hospital-based study performed between November 2012 and May 2013, on 300 renal transplant recipients attending Sudanese Kidney Association hospital in Khartoum state, Sudan, along with 300 normal healthy individuals matching the case in age and sex. Stool samples were collected for parasitological studies.

RESULTS: Out of the 300 renal transplant recipients: 242 (80.7%) were males mean age 43 ± 11.28 and 58 (19.3%) were females mean age 41 ± 13.41. Intestinal parasitic infection was observed in 118 participants and the overall frequency was 19.7%; of which 64 were cases (21.3%) and 54 (18.0%) were controls. Eight different species of intestinal parasites were identified; Entamoeba histolytica/dispar (7.5%), Entamoeba coli (6.5%), Giardia lambelia (3.2%), Cryptosporidium parvum (1.2%), Ascaris lumbricoides (0.6%), Enterobius vermicularis (0.3%), (0.2%) for each of Strongyloides stercoralis and Hymenolepis nana.}, } @article {pmid30157933, year = {2018}, author = {Catchpole, AP and Fullen, DJ and Noulin, N and Mann, A and Gilbert, AS and Lambkin-Williams, R}, title = {The manufacturing of human viral challenge agents for use in clinical studies to accelerate the drug development process.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {620}, pmid = {30157933}, issn = {1756-0500}, mesh = {Antibodies, Viral ; *Drug Discovery ; Humans ; Risk Assessment ; *Viruses ; }, abstract = {OBJECTIVE: This manuscript aims to provide an overview of the unique considerations and best practice principles associated with the manufacture of human viral challenge agents.

RESULTS: Considerations are discussed on the entire process from strain and viral source selection through manufacturing, safety and efficacy testing. The human viral challenge (HVC) model is an important tool to help accelerate the drug development process but producing viruses suitable for use in the model presents a unique set of challenges. There are many case by case decisions and risk assessments to consider and no clear international standard to produce viruses for this purpose. The authors present challenge virus manufacturing considerations from the current literature, regulatory guidance and their own direct experience in producing challenge viruses. The use of these viral stocks in clinical studies, as published in peer-reviewed journals, is also briefly described.}, } @article {pmid30157930, year = {2018}, author = {Rizwan, A and Jamal, A and Uzzaman, M and Fatima, S}, title = {Case report: lady with bone pains for 5 years-parathyroid carcinoma.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {617}, pmid = {30157930}, issn = {1756-0500}, mesh = {Female ; Humans ; Hypercalcemia ; *Hyperparathyroidism, Primary ; Middle Aged ; Pain/*etiology ; Pakistan ; Parathyroid Hormone ; Parathyroid Neoplasms/complications/*diagnosis/surgery ; Parathyroidectomy ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Parathyroid cancer is a rare cause of primary hyperparathyroidism. It presents a diagnostic and therapeutic challenge that may not be recognized preoperatively, and is often not conclusively identified during the operation. We present the case of a lady with backache and hypercalcemia, but with inadequate work-up for her condition for several years.

CASE PRESENTATION: A middle aged lady of Asian descent presented with backache. Initial work up revealed mild hypercalcemia, negative work up for multiple myeloma, negative sestamibi scan for parathyroid pathology. A phenomenally elevated parathormone (PTH) level-2105 pg/mL (16-87 pg/mL), and rising serum calcium, 15.1 mg/dL, (8.6-10.5 mg/dL), ordered years later prompted a repeat sestamibi scan and ultrasonography of neck. Based on these investigations, a diagnosis of primary hyperparathyroidism, with high suspicion of parathyroid cancer was made. The patient underwent surgical tumour resection, with subsequent histopathological confirmation of diagnosis.

CONCLUSION: In the setting of hypercalcemia, PTH level assessment is a must. This helps to differentiate between the parathyroid dependant and independent causes of high serum calcium, thereby encouraging a comprehensive pathway to the work up of the cause of hypercalcemia. The parathyroid cancer is a very rare cause of hypercalcemia, which needs to be considered in the differentials of primary hyperparathyroidism, particularly in the setting of high PTH levels.}, } @article {pmid30157909, year = {2018}, author = {Kerie, S and Menberu, M and Niguse, W}, title = {Prevalence and associated factors of postpartum depression in Southwest, Ethiopia, 2017: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {623}, pmid = {30157909}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Depression, Postpartum/*epidemiology ; Ethiopia/epidemiology ; Female ; Humans ; Odds Ratio ; Pregnancy ; Prevalence ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to determine the prevalence and associated factors of postpartum depression among mothers who gave birth within the last 12 months among hospitals of Southwest Ethiopia, 2017.

RESULT: The study revealed that 138 (33.82%) of mothers had postpartum depression. Unplanned pregnancy adjusted odds ratio (AOR) = 4.49, 95% CI (2.31, 8.71), age from 15 to 24 years AOR = 0.420, 95% CI (0.18, 0.98), having a chronic physical illness AOR = 7.71, 95% CI (2.34, 25.44), experiencing death of infant AOR = 4.12, (1.78, 9.51) and unstable marital condition AOR = 6.02, (2.79, 12.99) were significantly associated with postpartum depression. The prevalence of post-partum depression was found to be high. Therefore urgent attention must be given to this problem, in particular towards its early detection, so that morbidity could be reduced in this group of women.}, } @article {pmid30157830, year = {2018}, author = {Chen, M and Zuo, XA}, title = {Pollen limitation and resource limitation affect the reproductive success of Medicago sativa L.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {28}, pmid = {30157830}, issn = {1472-6785}, support = {31600252//National Natural Science Foundation of China/International ; Y729821001//CAS "Light of West China" Program/International ; 2016YFC0500506//China National Key Research and Development Plan/International ; }, abstract = {BACKGROUND: A large proportion of the flowers and ovules of plants do not develop into fruits and seeds. Plant reproduction may be limited because of pollen limitation and resource limitation. Medicago sativa L. is an ecologically important species in northwest China. We conducted a pollen supplementation experiment to determine the degree of pollen limitation in this species and detect the possible effects of resource allocation on pollen supplementation. We crossed two factors, pollen level (natural condition and hand pollinated) and resource level (control, water added, and fertilizer added), to estimate the effects of pollen addition and resource limitation on the opening of flowers and seed set. We also analyzed the floral characters, visitation frequency of pollinators and pollinator activity to estimate the effect of pollinators on the reproduction of M. sativa.

RESULTS: Our results indicated that addition of pollen to some flowers did not divert resources from other flowers and that the addition of pollen boosted the seed set per flower, with no effect on flower number. The primary effect of resource limitation was on the number of flowers produced; however, there was no significant effect on seed set per flower. These findings showed that pollen limitation was an important limiting factor for seed set. In addition, Andrena lebedevi Popov was identified as the most effective pollinator, and pollinator visiting and activity affected reproduction success in M. sativa.

CONCLUSIONS: We found outcrossing was dominant in the breeding system and insect pollination played an important role in outcrossing. These findings have identified the dominant factor influencing seed set of M. sativa. This study aspires to contribute to a better understanding of pollen limitation, resource limitation and reproductive success.}, } @article {pmid30157779, year = {2018}, author = {Rudra, P and Shi, WJ and Russell, P and Vestal, B and Tabakoff, B and Hoffman, P and Kechris, K and Saba, L}, title = {Predictive modeling of miRNA-mediated predisposition to alcohol-related phenotypes in mouse.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {639}, pmid = {30157779}, issn = {1471-2164}, support = {T15LM009451//U.S. National Library of Medicine/ ; T15 LM009451/LM/NLM NIH HHS/United States ; R24AA013162//National Institute on Alcohol Abuse and Alcoholism/ ; R24 AA013162/AA/NIAAA NIH HHS/United States ; R01AA021131//National Institute on Alcohol Abuse and Alcoholism/ ; P30 DA044223/DA/NIDA NIH HHS/United States ; P30DA044223//National Institute on Drug Abuse/ ; R01 AA021131/AA/NIAAA NIH HHS/United States ; }, mesh = {Alcohol-Related Disorders/*genetics ; Animals ; Bayes Theorem ; Genetic Predisposition to Disease/*genetics ; Mice ; MicroRNAs/*genetics ; *Models, Statistical ; *Phenotype ; Polymorphism, Single Nucleotide ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) are small non-coding RNAs that bind messenger RNAs and promote their degradation or repress their translation. There is increasing evidence of miRNAs playing an important role in alcohol related disorders. However, the role of miRNAs as mediators of the genetic effect on alcohol phenotypes is not fully understood. We conducted a high-throughput sequencing study to measure miRNA expression levels in alcohol naïve animals in the LXS panel of recombinant inbred (RI) mouse strains. We then combined the sequencing data with genotype data, microarry gene expression data, and data on alcohol-related behavioral phenotypes such as 'Drinking in the dark', 'Sleep time', and 'Low dose activation' from the same RI panel. SNP-miRNA-gene triplets with strong association within the triplet that were also associated with one of the 4 alcohol phenotypes were selected and a Bayesian network analysis was used to aggregate results into a directed network model.

RESULTS: We found several triplets with strong association within the triplet that were also associated with one of the alcohol phenotypes. The Bayesian network analysis found two networks where a miRNA mediates the genetic effect on the alcohol phenotype. The miRNAs were found to influence the expression of protein-coding genes, which in turn influences the quantitative phenotypes. The pathways in which these genes are enriched have been previously associated with alcohol-related traits.

CONCLUSION: This work enhances association studies by identifying miRNAs that may be mediating the association between genetic markers (SNPs) and the alcohol phenotypes. It suggests a mechanism of how genetic variants are affecting traits of interest through the modification of miRNA expression.}, } @article {pmid30157778, year = {2018}, author = {Pan, Y and Liu, Z and Rocheleau, H and Fauteux, F and Wang, Y and McCartney, C and Ouellet, T}, title = {Transcriptome dynamics associated with resistance and susceptibility against fusarium head blight in four wheat genotypes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {642}, pmid = {30157778}, issn = {1471-2164}, support = {project J-000412//Canadian Agriculture and Agri-Food Growing Forward 2 program/ ; projects J-000008 and J-001580//Genomics Research and Development Initiative/ ; National Wheat Improvement Program//Western Grains Research Foundation and Agriculture and Agri-Food Canada/ ; "Canadian Wheat Improvement" project A1-011652//National Research Council Canada/ ; }, mesh = {Chromosomes, Plant/genetics ; Disease Susceptibility ; Fusarium/*physiology ; *Gene Expression Profiling ; Gene Regulatory Networks ; *Genotype ; Plant Diseases/*microbiology ; Plant Growth Regulators/metabolism ; Plant Proteins/genetics ; Sequence Analysis, RNA ; Triticum/*genetics/immunology/metabolism/*microbiology ; }, abstract = {BACKGROUND: Fusarium head blight (FHB) of wheat in North America is caused mostly by the fungal pathogen Fusarium graminearum (Fg). Upon exposure to Fg, wheat initiates a series of cellular responses involving massive transcriptional reprogramming. In this study, we analyzed transcriptomics data of four wheat genotypes (Nyubai, Wuhan 1, HC374, and Shaw), at 2 and 4 days post inoculation (dpi) with Fg, using RNA-seq technology.

RESULTS: A total of 37,772 differentially expressed genes (DEGs) were identified, 28,961 from wheat and 8811 from the pathogen. The susceptible genotype Shaw exhibited the highest number of host and pathogen DEGs, including 2270 DEGs associating with FHB susceptibility. Protein serine/threonine kinases and LRR-RK were associated with susceptibility at 2 dpi, while several ethylene-responsive, WRKY, Myb, bZIP and NAC-domain containing transcription factors were associated with susceptibility at 4 dpi. In the three resistant genotypes, 220 DEGs were associated with resistance. Glutathione S-transferase (GST), membrane proteins and distinct LRR-RKs were associated with FHB resistance across the three genotypes. Genes with unique, high up-regulation by Fg in Wuhan 1 were mostly transiently expressed at 2 dpi, while many defense-associated genes were up-regulated at both 2 and 4 dpi in Nyubai; the majority of unique genes up-regulated in HC374 were detected at 4 dpi only. In the pathogen, most genes showed increased expression between 2 and 4 dpi in all genotypes, with stronger levels in the susceptible host; however two pectate lyases and a hydrolase were expressed higher at 2 dpi, and acetyltransferase activity was highly enriched at 4 dpi.

CONCLUSIONS: There was an early up-regulation of LRR-RKs, different between susceptible and resistant genotypes; subsequently, distinct sets of genes associated with defense response were up-regulated. Differences in expression profiles among the resistant genotypes indicate genotype-specific defense mechanisms. This study also shows a greater resemblance in transcriptomics of HC374 to Nyubai, consistent with their sharing of two FHB resistance QTLs on 3BS and 5AS, compared to Wuhan 1 which carries one QTL on 2DL in common with HC374.}, } @article {pmid30157777, year = {2018}, author = {Ostaszewski, M and Kieffer, E and Danoy, G and Schneider, R and Bouvry, P}, title = {Clustering approaches for visual knowledge exploration in molecular interaction networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {308}, pmid = {30157777}, issn = {1471-2105}, support = {AFR contract no. 9984150//Fonds National de la Recherche (LU)/ ; }, mesh = {*Algorithms ; Cluster Analysis ; Computational Biology/*methods ; *Computer Graphics ; Data Mining/*methods ; Databases, Factual ; *Gene Regulatory Networks ; Humans ; }, abstract = {BACKGROUND: Biomedical knowledge grows in complexity, and becomes encoded in network-based repositories, which include focused, expert-drawn diagrams, networks of evidence-based associations and established ontologies. Combining these structured information sources is an important computational challenge, as large graphs are difficult to analyze visually.

RESULTS: We investigate knowledge discovery in manually curated and annotated molecular interaction diagrams. To evaluate similarity of content we use: i) Euclidean distance in expert-drawn diagrams, ii) shortest path distance using the underlying network and iii) ontology-based distance. We employ clustering with these metrics used separately and in pairwise combinations. We propose a novel bi-level optimization approach together with an evolutionary algorithm for informative combination of distance metrics. We compare the enrichment of the obtained clusters between the solutions and with expert knowledge. We calculate the number of Gene and Disease Ontology terms discovered by different solutions as a measure of cluster quality. Our results show that combining distance metrics can improve clustering accuracy, based on the comparison with expert-provided clusters. Also, the performance of specific combinations of distance functions depends on the clustering depth (number of clusters). By employing bi-level optimization approach we evaluated relative importance of distance functions and we found that indeed the order by which they are combined affects clustering performance. Next, with the enrichment analysis of clustering results we found that both hierarchical and bi-level clustering schemes discovered more Gene and Disease Ontology terms than expert-provided clusters for the same knowledge repository. Moreover, bi-level clustering found more enriched terms than the best hierarchical clustering solution for three distinct distance metric combinations in three different instances of disease maps.

CONCLUSIONS: In this work we examined the impact of different distance functions on clustering of a visual biomedical knowledge repository. We found that combining distance functions may be beneficial for clustering, and improve exploration of such repositories. We proposed bi-level optimization to evaluate the importance of order by which the distance functions are combined. Both combination and order of these functions affected clustering quality and knowledge recognition in the considered benchmarks. We propose that multiple dimensions can be utilized simultaneously for visual knowledge exploration.}, } @article {pmid30157774, year = {2018}, author = {Shi, Q and Lan, P and Huang, D and Hua, X and Jiang, Y and Zhou, J and Yu, Y}, title = {Diversity of virulence level phenotype of hypervirulent Klebsiella pneumoniae from different sequence type lineage.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {94}, pmid = {30157774}, issn = {1471-2180}, abstract = {BACKGROUND: Hypervirulent Klebsiella pneumoniae (hvKP) is emerging around the Asian-Pacific region and it is the major cause of the community-acquired pyogenic liver abscesses. Multidrug-resistant hypervirulent Klebsiella pneumoniae (MDR-hvKP) isolates were reported in France, China and Taiwan. However, the international-ally agreed definition for hvKP and the virulence level of hvKP are not clear.

RESULTS: In this study, 56 hvKP isolates were collected from March 2008 to June 2012 and investigated by string test, capsule serotyping, multilocus sequence typing (MLST), virulence gene detection and serum resistance assay. Among the 56 K. pneumoniae isolates, 64.3% had the hypermucoviscosity phenotype, meanwhile, 64.3% were the K1 serotype and 19.6% were the K2 serotype. Within the K1 serotype, 94.4% were ST23, and within the K2 serotype, ST65, ST86 and ST375 accounted for the same percentage 27.3%. The serum resistance showed statistically normal distribution. According to the 50% lethal dose of Galleria. mellonella infection model, hvKP isolates were divided into high virulence level group and moderate virulence level group. The ability of each method evaluating the virulence level of hvKP was assessed using the area under the receiver operating characteristic curve.

CONCLUSIONS: K1 ST23 K. pneumoniae was the most prevalent clone of the hvKP. However, K1 ST23 K. pneumoniae was the dominant clone in the moderate virulence level group. MLST was a relatively reliable evaluation method to discriminate the virulence level of hvKP in our study.}, } @article {pmid30157773, year = {2018}, author = {Riddell, N and Faou, P and Crewther, SG}, title = {Short term optical defocus perturbs normal developmental shifts in retina/RPE protein abundance.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {18}, pmid = {30157773}, issn = {1471-213X}, support = {RFA Understanding Disease Start-up Grant//La Trobe University/International ; }, abstract = {BACKGROUND: Myopia (short-sightedness) affects approximately 1.4 billion people worldwide, and prevalence is increasing. Animal models induced by defocusing lenses show striking similarity with human myopia in terms of morphology and the implicated genetic pathways. Less is known about proteome changes in animals. Thus, the present study aimed to improve understanding of protein pathway responses to lens defocus, with an emphasis on relating expression changes to no lens control development and identifying bidirectional and/or distinct pathways across myopia and hyperopia (long-sightedness) models.

RESULTS: Quantitative label-free proteomics and gene set enrichment analysis (GSEA) were used to examine protein pathway expression in the retina/RPE of chicks following 6 h and 48 h of myopia induction with - 10 dioptre (D) lenses, hyperopia induction with +10D lenses, or normal no lens rearing. Seventy-one pathways linked to cell development and neuronal maturation were differentially enriched between 6 and 48 h in no lens chicks. The majority of these normal developmental changes were disrupted by lens-wear (47 of 71 pathways), however, only 11 pathways displayed distinct expression profiles across the lens conditions. Most notably, negative lens-wear induced up-regulation of proteins involved in ATP-driven ion transport, calcium homeostasis, and GABA signalling between 6 and 48 h, while the same proteins were down-regulated over time in normally developing chicks. Glutamate and bicarbonate/chloride transporters were also down-regulated over time in normally developing chicks, and positive lens-wear inhibited this down-regulation.

CONCLUSIONS: The chick retina/RPE proteome undergoes extensive pathway expression shifts during normal development. Most of these pathways are further disrupted by lens-wear. The identified expression patterns suggest close interactions between neurotransmission (as exemplified by increased GABA receptor and synaptic protein expression), cellular ion homeostasis, and associated energy resources during myopia induction. We have also provided novel evidence for changes to SLC-mediated transmembrane transport during hyperopia induction, with potential implications for signalling at the photoreceptor-bipolar synapse. These findings reflect a key role for perturbed neurotransmission and ionic homeostasis in optically-induced refractive errors, and are predicted by our Retinal Ion Driven Efflux (RIDE) model.}, } @article {pmid30157769, year = {2018}, author = {Yang, Y and Lin, L and Ferguson, DK and Wang, Y}, title = {Macrofossil evidence unveiling evolution of male cones in Ephedraceae (Gnetidae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {125}, pmid = {30157769}, issn = {1471-2148}, support = {31770211, 31270238, 31470301//National Natural Science Foundation of China/International ; }, mesh = {*Biological Evolution ; Forests ; *Fossils ; Pollination ; Tracheophyta/*anatomy & histology/*physiology ; }, abstract = {BACKGROUND: Male cones of modern Ephedraceae are compound and compact. No fossil evidence has so far been found to support an origin of the compact compound male cone from a hypothetical loosely-arranged shoot system.

RESULTS: Here we describe a new macrofossil taxon, Eamesia chinensis Yang, Lin, Ferguson et Wang, gen. et sp. nov., from the Early Cretaceous of western Liaoning, northeastern China. It was an ephedroid shrub bearing male spikes terminal to twigs, but differs from modern Ephedraceae by its loosely-arranged male cones, the axillary male shoot consisting of an elongated synangiophore on which leaf-like foliar organs were inserted, and four sessile synangia terminal to the apex.

CONCLUSIONS: The morphology of this fossil suggests that the modern compact male cone of Ephedra was indeed derived from a once loosely-arranged shoot system, and the male reproductive unit originated from a once elongated axillary male shoot. This new fossil species thus provides a transitional link from the hypothetical ancestral shoot system to the modern compact morphology. Changes of habitat from closed humid forests to open dry deserts and shifts of the pollination syndrome may have acted as the driving forces behind this morphological evolution.}, } @article {pmid30157765, year = {2018}, author = {Chu, XL and Zhang, BW and Zhang, QG and Zhu, BR and Lin, K and Zhang, DY}, title = {Temperature responses of mutation rate and mutational spectrum in an Escherichia coli strain and the correlation with metabolic rate.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {126}, pmid = {30157765}, issn = {1471-2148}, support = {31725006 and 31670376//National Natural Science Foundation of China/International ; B13008//State Administration of Foreign Experts Affairs/International ; 2017EYT20 and 2017STUD19//Ministry of Education of the People's Republic of China/International ; }, mesh = {Base Pairing/genetics ; Escherichia coli/*genetics/growth & development/*metabolism ; INDEL Mutation/genetics ; Mutation/*genetics ; *Mutation Rate ; *Temperature ; }, abstract = {BACKGROUND: Temperature is a major determinant of spontaneous mutation, but the precise mode, and the underlying mechanisms, of the temperature influences remain less clear. Here we used a mutation accumulation approach combined with whole-genome sequencing to investigate the temperature dependence of spontaneous mutation in an Escherichia coli strain. Experiments were performed under aerobic conditions at 25, 28 and 37 °C, three temperatures that were non-stressful for the bacterium but caused significantly different bacterial growth rates.

RESULTS: Mutation rate did not differ between 25 and 28 °C, but was higher at 37 °C. Detailed analyses of the molecular spectrum of mutations were performed; and a particularly interesting finding is that higher temperature led to a bias of mutation to coding, relative to noncoding, DNA. Furthermore, the temperature response of mutation rate was extremely similar to that of metabolic rate, consistent with an idea that metabolic rate predicts mutation rate.

CONCLUSIONS: Temperature affects mutation rate and the types of mutation supply, both being crucial for the opportunity of natural selection. Our results help understand how temperature drives evolutionary speed of organisms and thus the global patterns of biodiversity. This study also lend support to the metabolic theory of ecology for linking metabolic rate and molecular evolution rate.}, } @article {pmid30157763, year = {2018}, author = {Xu, Y and Liu, F and Chen, S and Wu, J and Hu, Y and Zhu, B and Sun, Z}, title = {In vivo evolution of drug-resistant Mycobacterium tuberculosis in patients during long-term treatment.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {640}, pmid = {30157763}, issn = {1471-2164}, support = {2013ZX10003009//the Key Project Specialized for Infectious Diseases of the Chinese Ministry of Health/ ; KJ2017CX053//Tongzhou District Science and Technology Committee/ ; 31601081//National Natural Science Foundation of China (CN)/ ; }, mesh = {Antitubercular Agents/pharmacology/therapeutic use ; *Evolution, Molecular ; Genotype ; Humans ; Microbial Sensitivity Tests ; Mutation ; Mycobacterium tuberculosis/drug effects/*genetics/*physiology ; Polymorphism, Single Nucleotide ; Time Factors ; Tuberculosis, Multidrug-Resistant/*genetics ; }, abstract = {BACKGROUND: In the current scenario, the drug-resistant tuberculosis is a significant challenge in the control of tuberculosis worldwide. In order to investigate the in vivo evolution of drug-resistant M. tuberculosis, the present study envisaged sequencing of the draft genomes of 18 serial isolates from four pre-extensively drug-resistant (pre-XDR) tuberculosis patients for continuous genetic alterations.

RESULTS: All of the isolates harbored single nucleotide polymorphisms (SNPs) ranging from 1303 to 1309 with M. tuberculosis H37Rv as the reference. SNPs ranged from 0 to 12 within patients. The evolution rates were higher than the reported SNPs of 0.5 in the four patients. All the isolates exhibited mutations at sites of known drug targets, while some contained mutations in uncertain drug targets including folC, proZ, and pyrG. The compensatory substitutions for rescuing these deleterious mutations during evolution were only found in RpoC I491T in one patient. Many loci with microheterogeneity showed transient mutations in different isolates. Ninety three SNPs exhibited significant association with refractory pre-XDR TB isolates.

CONCLUSIONS: Our results showed evolutionary changes in the serial genetic characteristics of the pre-XDR TB patients due to accumulation of the fixed drug-resistant related mutations, and the transient mutations under continuous antibiotics pressure over several years.}, } @article {pmid30157762, year = {2018}, author = {Butt, H and Jamil, M and Wang, JY and Al-Babili, S and Mahfouz, M}, title = {Engineering plant architecture via CRISPR/Cas9-mediated alteration of strigolactone biosynthesis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {174}, pmid = {30157762}, issn = {1471-2229}, support = {CRG4//King Abdullah University of Science and Technology/ ; }, mesh = {*CRISPR-Cas Systems ; Dioxygenases/*genetics/metabolism ; *Gene Expression Regulation, Plant ; Heterocyclic Compounds, 3-Ring/*metabolism ; Lactones/*metabolism ; Oryza/*genetics/metabolism ; Plant Growth Regulators/*metabolism ; Plant Proteins/*genetics/metabolism ; }, abstract = {BACKGROUND: Precision plant genome engineering holds much promise for targeted improvement of crop traits via unprecedented single-base level control over the genetic material. Strigolactones (SLs) are a key determinant of plant architecture, known for their role in inhibiting shoot branching (tillering).

RESULTS: We used CRISPR/Cas9 in rice (Oryza sativa) for targeted disruption of CAROTENOID CLEAVAGE DIOXYGENASE 7 (CCD7), which controls a key step in SL biosynthesis. The ccd7 mutants exhibited a striking increase in tillering, combined with a reduced height, which could be rescued by application of the synthetic SL analog GR24. Striga germination assays and liquid chromatography-mass spectrometry analysis showed that root exudates of ccd7 mutants were also SL deficient.

CONCLUSIONS: Taken together, our results show the potential and feasibility of the use of the CRISPR/Cas9 system for targeted engineering of plant architecture and for elucidating the molecular underpinnings of architecture-related traits.}, } @article {pmid30157760, year = {2018}, author = {Velie, BD and Fegraeus, KJ and Solé, M and Rosengren, MK and Røed, KH and Ihler, CF and Strand, E and Lindgren, G}, title = {A genome-wide association study for harness racing success in the Norwegian-Swedish coldblooded trotter reveals genes for learning and energy metabolism.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {80}, pmid = {30157760}, issn = {1471-2156}, support = {H-15-47-075//Swedish-Norwegian Foundation for Equine Research/ ; }, abstract = {BACKGROUND: Although harness racing is of high economic importance to the global equine industry, significant genomic resources have yet to be applied to mapping harness racing success. To identify genomic regions associated with harness racing success, the current study performs genome-wide association analyses with three racing performance traits in the Norwegian-Swedish Coldblooded Trotter using the 670 K Axiom Equine Genotyping Array.

RESULTS: Following quality control, 613 horses and 359,635 SNPs were retained for further analysis. After strict Bonferroni correction, nine genome-wide significant SNPs were identified for career earnings. No genome-wide significant SNPs were identified for number of gallops or best km time. However, four suggestive genome-wide significant SNPs were identified for number of gallops, while 19 were identified for best km time. Multiple genes related to intelligence, energy metabolism, and immune function were identified as potential candidate genes for harness racing success.

CONCLUSIONS: Apart from the physiological requirements needed for a harness racing horse to be successful, the results of the current study also advocate learning ability and memory as important elements for harness racing success. Further exploration into the mental capacity required for a horse to achieve racing success is likely warranted.}, } @article {pmid30157759, year = {2018}, author = {Clausen, PTLC and Aarestrup, FM and Lund, O}, title = {Rapid and precise alignment of raw reads against redundant databases with KMA.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {307}, pmid = {30157759}, issn = {1471-2105}, support = {643476//European Union's Horizon 2020 research and innovation programme/ ; }, mesh = {*Algorithms ; Computational Biology/*methods ; Computer Simulation ; *Databases, Factual ; *Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Alignment ; Sequence Analysis, DNA/*methods ; *Software ; }, abstract = {BACKGROUND: As the cost of sequencing has declined, clinical diagnostics based on next generation sequencing (NGS) have become reality. Diagnostics based on sequencing will require rapid and precise mapping against redundant databases because some of the most important determinants, such as antimicrobial resistance and core genome multilocus sequence typing (MLST) alleles, are highly similar to one another. In order to facilitate this, a novel mapping method, KMA (k-mer alignment), was designed. KMA is able to map raw reads directly against redundant databases, it also scales well for large redundant databases. KMA uses k-mer seeding to speed up mapping and the Needleman-Wunsch algorithm to accurately align extensions from k-mer seeds. Multi-mapping reads are resolved using a novel sorting scheme (ConClave scheme), ensuring an accurate selection of templates.

RESULTS: The functionality of KMA was compared with SRST2, MGmapper, BWA-MEM, Bowtie2, Minimap2 and Salmon, using both simulated data and a dataset of Escherichia coli mapped against resistance genes and core genome MLST alleles. KMA outperforms current methods with respect to both accuracy and speed, while using a comparable amount of memory.

CONCLUSION: With KMA, it was possible map raw reads directly against redundant databases with high accuracy, speed and memory efficiency.}, } @article {pmid30157758, year = {2018}, author = {Liao, F and Gu, W and Yang, Z and Mo, Z and Fan, L and Guo, Y and Fu, X and Xu, W and Li, C and Dai, J}, title = {Molecular characteristics of Staphylococcus aureus isolates from food surveillance in southwest China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {91}, pmid = {30157758}, issn = {1471-2180}, abstract = {BACKGROUND: Staphylococcal food poisoning (SFP) is one of the most common food-borne diseases in the world. Pulsed-field gel electrophoresis (PFGE), multilocus sequence typing (MLST) and spa typing methods were used to characterize Staphylococcus aureus isolates from food surveillance during 2013-2015 in southwest China, and Staphylococcal cassette chromosome mec (SCCmec) typing was used for methicillin-resistant S. aureus (MRSA). Isolates were also examined for their antibiotic resistance and carriage of virulence genes.

RESULTS: Isolation rate of S. aureus was 2.60% during the three years' surveillance and 29.50% of them were MRSA. All the S. aureus had hla genes (100%), 14.34% of the strains had tst, and 16.73% had PVL. 163 PFGE-SmaI patterns, 41 ST types and 36 spa types were obtained for all the S. aureus. Among them, ST6-t701 (13.15%), ST7-t091 (12.75%), ST59-t437 (9.96%) and ST5-t002 (7.57%) were the prevalent genotypes. Most of MRSA in this study belonged to SCCmec IV and V, accounted for 74.32% and 20.27% respectively. ST6-SCCmec IV-t701 (36.50%) was the most prevalent clone among isolates from food, followed by ST59-SCCmec V-t437 (20.30%), ST5-SCCmec IV-t002 (12.20%) and ST59-SCCmec IV-t437 (12.20%). Some strains had the identical PFGE patterns, ST and spa types with isolates from patients.

CONCLUSIONS: S. aureus isolated from food in southwest China displayed heterogeneity. Isolates had the same genotype profiles with isolates from patients, indicating high homology.}, } @article {pmid30157757, year = {2018}, author = {Zhang, Y and Li, W and Lin, Y and Zhang, L and Wang, C and Xu, R}, title = {Construction of a high-density genetic map and mapping of QTLs for soybean (Glycine max) agronomic and seed quality traits by specific length amplified fragment sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {641}, pmid = {30157757}, issn = {1471-2164}, support = {31501329//National Natural Science Foundation of China/ ; ZR2015YL070//Natural Science Foundation of Shandong Province/ ; 2016ZDJS10A03-03//Key Research and Development Program of Shandong Province/ ; }, mesh = {Chromosome Mapping/*methods ; Epistasis, Genetic ; Phenotype ; Quantitative Trait Loci/*genetics ; Seeds/*growth & development ; *Sequence Analysis ; Soybeans/*genetics/*growth & development ; }, abstract = {BACKGROUND: Soybean is not only an important oil crop, but also an important source of edible protein and industrial raw material. Yield-traits and quality-traits are increasingly attracting the attention of breeders. Therefore, fine mapping the QTLs associated with yield-traits and quality-traits of soybean would be helpful for soybean breeders. In the present study, a high-density linkage map was constructed to identify the QTLs for the yield-traits and quality-traits, using specific length amplified fragment sequencing (SLAF-seq).

RESULTS: SLAF-seq was performed to screen SLAF markers with 149 F8:11 individuals from a cross between a semi wild soybean, 'Huapidou', and a cultivated soybean, 'Qihuang26', which generated 400.91 M paired-end reads. In total, 53,132 polymorphic SLAF markers were obtained. The genetic linkage map was constructed by 5111 SLAF markers with segregation type of aa×bb. The final map, containing 20 linkage groups (LGs), was 2909.46 cM in length with an average distance of 0.57 cM between adjacent markers. The average coverage for each SLAF marker on the map was 81.26-fold in the male parent, 45.79-fold in the female parent, and 19.84-fold average in each F8:11 individual. According to the high-density map, 35 QTLs for plant height (PH), 100-seeds weight (SW), oil content in seeds (Oil) and protein content in seeds (Protein) were found to be distributed on 17 chromosomes, and 14 novel QTLs were identified for the first time. The physical distance of 11 QTLs was shorter than 100 Kb, suggesting a direct opportunity to find candidate genes. Furthermore, three pairs of epistatic QTLs associated with Protein involving 6 loci on 5 chromosomes were identified. Moreover, 13, 14, 7 and 9 genes, which showed tissue-specific expression patterns, might be associated with PH, SW, Oil and Protein, respectively.

CONCLUSIONS: With SLAF-sequencing, some novel QTLs and important QTLs for both yield-related and quality traits were identified based on a new, high-density linkage map. Moreover, 43 genes with tissue-specific expression patterns were regarded as potential genes in further study. Our findings might be beneficial to molecular marker-assisted breeding, and could provide detailed information for accurate QTL localization.}, } @article {pmid30157755, year = {2018}, author = {Xie, X and Müller, N}, title = {Enzymes involved in the anaerobic degradation of phenol by the sulfate-reducing bacterium Desulfatiglans anilini.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {93}, pmid = {30157755}, issn = {1471-2180}, abstract = {BACKGROUND: The sulfate-reducing bacterium Desulfatiglans anilini can grow with phenol as sole source of carbon and energy under strictly anaerobic, sulfate-reducing conditions. In the nitrate-reducing bacterium Thauera aromatica, the enzymes involved in phenol degradation have been well elucidated, whereas the anaerobic phenol degradation pathway by D. anilini was not studied in detail yet.

RESULTS: The pathway of anaerobic phenol degradation by the sulfate-reducing bacterium Desulfatiglans anilini was studied by identification of genes coding for phenylphosphate synthase (encoded by pps genes) and phenylphosphate carboxylase (encoded by ppc genes) in the genome of D. anilini, by analysis of the transcription and translation of pps-ppc genes, and by measurement of phenylphosphate synthase activity in cell-free extracts of phenol-grown cells. The majority of genes involved in phenol degradation were found to be organized in one gene cluster. The gene cluster contained genes ppsα (phenylphosphate synthase alpha subunit), ppsβ (phenylphosphate synthase beta subunit), ppcβ (phenylphosphate carboxylase beta subunit), as well as 4-hydroxybenzoyl-CoA ligase and 4-hydroxylbenzoyl-CoA reductase-encoding genes. The genes ppsγ (phenylphosphate synthase gamma subunit), ppcα (phenylphosphate carboxylase alpha subunit) and ppcδ (phenylphosphate carboxylase delta subunit) were located elsewhere in the genome of D. anilini, and no obvious homologue of ppcγ (phenylphosphate carboxylase gamma subunit) was found in the genome. Induction of genes pps and ppc during growth on phenol was confirmed by reverse transcription polymerase chain reaction. Total proteome analysis revealed that the abundance of enzymes encoded by the gene cluster under study was much higher in phenol-grown cells than that in benzoate-grown cells. In in-vitro enzyme assays with cell-free extracts of phenol-grown cells, phenylphosphate was formed from phenol in the presence of ATP, Mg2+, Mn2+, K+ as co-factors.

CONCLUSIONS: The genes coding for enzymes involved in the anaerobic phenol degradation pathway were identified in the sulfate-reducing bacterium D. anilini. The results indicate that the first steps of anaerobic phenol degradation in D. anilini are phosphorylation of phenol to phenylphosphate by phenylphosphate synthase and carboxylation of phenylphosphate by phenylphosphate carboxylase.}, } @article {pmid30157754, year = {2018}, author = {Zhang, Y and Yu, X and Yu, E and Wang, N and Cai, Q and Shuai, Q and Yan, F and Jiang, L and Wang, H and Liu, J and Chen, Y and Li, Z and Jiang, Q}, title = {Changes in gut microbiota and plasma inflammatory factors across the stages of colorectal tumorigenesis: a case-control study.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {92}, pmid = {30157754}, issn = {1471-2180}, abstract = {BACKGROUND: Colorectal cancer (CRC) is a common malignant gastrointestinal tumor. In China, CRC is the 5th most commonly diagnosed cancer. The vast majority of CRC cases are sporadic and evolve with the adenoma-carcinoma sequence. There is mounting evidence indicating that gut microbiota and inflammation play important roles in the development of CRC although study results are not entirely consistent. In the current study, we investigated the changes in the CRC-associated bacteria and plasma inflammatory factors and their relationships based on data from a case-control study of Han Chinese. We included 130 initially diagnosed CRC patients, 88 advanced colorectal adenoma patients (A-CRA), 62 patients with benign intestinal polyps and 130 controls.

RESULTS: Fecal microbiota composition was obtained using 16S ribosomal DNA (16S rDNA) sequencing. PCOA analysis showed structural differences in microbiota among the four study groups (P = 0.001, Unweighted Unifrac). Twenty-four CRC-associated bacteria were selected by a two-step statistical method and significant correlations were observed within these microbes. CRC-associated bacteria were found to change with the degree of malignancy. Plasma C-reactive protein (CRP) and soluble tumor necrosis factor II (sTNFR-II) displayed significant differences among the four study groups and increased with adenoma-carcinoma sequence. The correlations of CRP and sTNFR-II with several CRC-associated microbes were also explored.

CONCLUSIONS: CRC-associated species and plasma inflammatory factors tended to change along the adenoma-carcinoma sequence. Several CRC-associated bacteria were correlated with CRP and sTNFR-II. It is likely that gut microbiome and inflammation gradually form a microenvironment that is associated with CRC development.}, } @article {pmid30157751, year = {2018}, author = {Mustonen, V and Kesäniemi, J and Lavrinienko, A and Tukalenko, E and Mappes, T and Watts, PC and Jurvansuu, J}, title = {Fibroblasts from bank voles inhabiting Chernobyl have increased resistance against oxidative and DNA stresses.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {17}, pmid = {30157751}, issn = {1471-2121}, mesh = {Animals ; Antioxidants/metabolism ; Arvicolinae/*metabolism ; Cell Cycle Checkpoints ; Cell Death ; Cell Line ; Cell Survival ; *Chernobyl Nuclear Accident ; DNA/*metabolism ; DNA Damage ; Fibroblasts/*metabolism/*pathology ; G2 Phase ; Gamma Rays ; Male ; Oxidants/metabolism ; *Oxidative Stress ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {BACKGROUND: Elevated levels of environmental ionizing radiation can be a selective pressure for wildlife by producing reactive oxygen species and DNA damage. However, the underlying molecular mechanisms that are affected are not known.

RESULTS: We isolated skin fibroblasts from bank voles (Myodes glareolus) inhabiting the Chernobyl nuclear power plant accident site where background radiation levels are about 100 times greater than in uncontaminated areas. After a 10 Gy dose of gamma radiation fibroblasts from Chernobyl animals recovered faster than fibroblasts isolated from bank voles living in uncontaminated control area. The Chernobyl fibroblasts were able to sustain significantly higher doses of an oxidant and they had, on average, a higher total antioxidant capacity than the control fibroblasts. Furthermore, the Chernobyl fibroblasts were also significantly more resistant than the control fibroblasts to continuous exposure to three DNA damaging drugs. After drug treatment transcription of p53-target gene pro-apoptotic Bax was higher in the control than in the Chernobyl fibroblasts.

CONCLUSION: Fibroblasts isolated from bank voles inhabiting Chernobyl nuclear power plant accident site show elevated antioxidant levels, lower sensitivity to apoptosis, and increased resistance against oxidative and DNA stresses. These cellular qualities may help bank voles inhabiting Chernobyl to cope with environmental radioactivity.}, } @article {pmid30157750, year = {2018}, author = {He, J and Fang, T and Zhang, Z and Huang, B and Zhu, X and Xiong, Y}, title = {PseUI: Pseudouridine sites identification based on RNA sequence information.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {306}, pmid = {30157750}, issn = {1471-2105}, support = {21403002//National Natural Science Foundation of China/ ; 31601074//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Computational Biology/*methods ; Humans ; Mice ; Pseudouridine/*analysis/chemistry ; RNA/*analysis/chemistry ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, RNA/*methods ; Support Vector Machine ; }, abstract = {BACKGROUND: Pseudouridylation is the most prevalent type of posttranscriptional modification in various stable RNAs of all organisms, which significantly affects many cellular processes that are regulated by RNA. Thus, accurate identification of pseudouridine (Ψ) sites in RNA will be of great benefit for understanding these cellular processes. Due to the low efficiency and high cost of current available experimental methods, it is highly desirable to develop computational methods for accurately and efficiently detecting Ψ sites in RNA sequences. However, the predictive accuracy of existing computational methods is not satisfactory and still needs improvement.

RESULTS: In this study, we developed a new model, PseUI, for Ψ sites identification in three species, which are H. sapiens, S. cerevisiae, and M. musculus. Firstly, five different kinds of features including nucleotide composition (NC), dinucleotide composition (DC), pseudo dinucleotide composition (pseDNC), position-specific nucleotide propensity (PSNP), and position-specific dinucleotide propensity (PSDP) were generated based on RNA segments. Then, a sequential forward feature selection strategy was used to gain an effective feature subset with a compact representation but discriminative prediction power. Based on the selected feature subsets, we built our model by using a support vector machine (SVM). Finally, the generalization of our model was validated by both the jackknife test and independent validation tests on the benchmark datasets. The experimental results showed that our model is more accurate and stable than the previously published models. We have also provided a user-friendly web server for our model at http://zhulab.ahu.edu.cn/PseUI , and a brief instruction for the web server is provided in this paper. By using this instruction, the academic users can conveniently get their desired results without complicated calculations.

CONCLUSION: In this study, we proposed a new predictor, PseUI, to detect Ψ sites in RNA sequences. It is shown that our model outperformed the existing state-of-art models. It is expected that our model, PseUI, will become a useful tool for accurate identification of RNA Ψ sites.}, } @article {pmid30156969, year = {2019}, author = {Yu, L}, title = {Global Air-Sea Fluxes of Heat, Fresh Water, and Momentum: Energy Budget Closure and Unanswered Questions.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {227-248}, doi = {10.1146/annurev-marine-010816-060704}, pmid = {30156969}, issn = {1941-0611}, abstract = {The ocean interacts with the atmosphere via interfacial exchanges of momentum, heat (via radiation and convection), and fresh water (via evaporation and precipitation). These fluxes, or exchanges, constitute the ocean-surface energy and water budgets and define the ocean's role in Earth's climate and its variability on both short and long timescales. However, direct flux measurements are available only at limited locations. Air-sea fluxes are commonly estimated from bulk flux parameterization using flux-related near-surface meteorological variables (winds, sea and air temperatures, and humidity) that are available from buoys, ships, satellite remote sensing, numerical weather prediction models, and/or a combination of any of these sources. Uncertainties in parameterization-based flux estimates are large, and when they are integrated over the ocean basins, they cause a large imbalance in the global-ocean budgets. Despite the significant progress that has been made in quantifying surface fluxes in the past 30 years, achieving a global closure of ocean-surface energy and water budgets remains a challenge for flux products constructed from all data sources. This review provides a personal perspective on three questions: First, to what extent can time-series measurements from air-sea buoys be used as benchmarks for accuracy and reliability in the context of the budget closures? Second, what is the dominant source of uncertainties for surface flux products, the flux-related variables or the bulk flux algorithms? And third, given the coupling between the energy and water cycles, precipitation and surface radiation can act as twin budget constraints-are the community-standard precipitation and surface radiation products pairwise compatible?}, } @article {pmid30156749, year = {2018}, author = {Christou, M and Iliopoulou, M and Witten, PE and Koumoundouros, G}, title = {Segmentation pattern of zebrafish caudal fin is affected by developmental temperature and defined by multiple fusions between segments.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {6-7}, pages = {330-340}, doi = {10.1002/jez.b.22825}, pmid = {30156749}, issn = {1552-5015}, support = {09SYN-24-619//Ministry of Education, Religious Affairs, Culture and Sports, Greece/ ; }, abstract = {Caudal-fin lepidotrichia is composed of numerous segments, which are linked to each other by intersegmental joints. During fish growth, lepidotrichia elongate by the addition of new segments at their distal margin, whereas the length of each segment remains constant after it is formed. In the present paper, we examined whether the water temperature affects the segmentation pattern of the juvenile and adult caudal fin. For this purpose, zebrafish (Danio rerio) embryos and larvae were exposed to three different temperature conditions (24°C, 28°C, and 32°C) from the pharyngula stage (1 day postfertilization [dpf]) to metamorphosis, whereas the control temperature (28°C) was applied to all the groups before and after this period. Results demonstrated that water temperature had a significant effect on the length of the segments of each lepidotrichium, at both the juvenile and adult stages. Moreover, at higher temperatures, there was a significant proximal shift of the position of the first bifurcation of the second lepidotrichium of the dorsal lobe. At all the experimental conditions, the length of proximal segment was not constant during fish growth, but it followed a discontinuous saltatory growth. Histological analysis of the proximal lepidotrichia segments revealed that the observed apparent growth of segments is the result of fusions between segments. Fusion occurs not by mineralization of the intersegmental joints, but by bone deposition around the joints.}, } @article {pmid30156533, year = {2018}, author = {Huang, LN and Xi, ZW and Li, Y and Hui, FL}, title = {Sugiyamaella xiaguanensis f.a., sp. nov., a yeast species isolated from rotting wood.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3307-3310}, doi = {10.1099/ijsem.0.002988}, pmid = {30156533}, issn = {1466-5034}, mesh = {Base Composition ; Benzyl Alcohols ; Cellobiose ; China ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Glucosides ; Mycological Typing Techniques ; *Phylogeny ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Wood/*microbiology ; Xylose ; }, abstract = {Three strains representing a novel yeast species, Sugiyamaella xiaguanensis f.a., sp. nov. (type strain NYNU 161041T=CICC 33167T=CBS 14696T), were isolated from rotting wood samples collected in Henan and Yunnan Provinces, PR China. The novel species is able to assimilate cellobiose, salicin and d-xylose, which was typical of the species of the genus Sugiyamaella. Analysis of the D1/D2 domains of the large subunit rRNA gene and internal transcribed spacer regions of these strains showed that this species was related to Sugiyamaella lignohabitans and Sugiyamaella marionensis, its closest relatives. Su. xiaguanensis sp. nov. differed by 1.4 % nucleotide substitutions from Su. lignohabitans, and by 1.9 % nucleotide substitutions from Su. marionensis in the D1/D2 sequences. The ITS sequences of Su. xiaguanensis sp. nov. displayed more than 6.5 % nucleotide substitutions from the latter two species, showing that it is a genetically separate species.}, } @article {pmid30156532, year = {2018}, author = {Doijad, SP and Poharkar, KV and Kale, SB and Kerkar, S and Kalorey, DR and Kurkure, NV and Rawool, DB and Malik, SVS and Ahmad, RY and Hudel, M and Chaudhari, SP and Abt, B and Overmann, J and Weigel, M and Hain, T and Barbuddhe, SB and Chakraborty, T}, title = {Listeria goaensis sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3285-3291}, doi = {10.1099/ijsem.0.002980}, pmid = {30156532}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; India ; Listeria/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhizophoraceae ; Sequence Analysis, DNA ; *Wetlands ; }, abstract = {Two Listeria-like isolates obtained from mangrove swamps in Goa, India were characterized using polyphasic combinations of phenotypic, chemotaxonomic and whole-genome sequence (WGS)-based approaches. The isolates presented as short, non-spore-forming, Gram-positive rods, that were non-motile, oxidase-negative, catalase-positive and exhibited α-haemolysis on 5 % sheep- and horse-blood agar plates. The 16S rRNA gene sequences exhibited 93.7-99.7 % nucleotide identity to other Listeria species and had less than 92 % nucleotide identity to species of closely related genera, indicating that the isolates are de facto members of the genus Listeria. Their overall fatty acid composition resembled that of other Listeria species, with quantitative differences in iso C15 : 0, anteiso C15 : 0, iso C16 : 0, C16 : 0, iso C17 : 0 and anteiso C17 : 0 fatty acid profiles. Phylogeny based on 406 core coding DNA sequences grouped these two isolates in a monophyletic clade within the genus Listeria. WGS-based average nucleotide identity and in silico DNA-DNA hybridization values were lower than the recommended cut-off values of 95 and 70 %, respectively, to the other Listeria species, indicating that they are founding members of a novel Listeria species. We suggest the name Listeriagoaensis sp. nov. be created and the type strain is ILCC801T (=KCTC 33909;=DSM 29886;=MCC 3285).}, } @article {pmid30156531, year = {2018}, author = {Song, J and Jeon, HT and Lim, Y and Joung, Y and Cho, JC}, title = {Winogradskyella aurantiaca sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3260-3265}, doi = {10.1099/ijsem.0.002977}, pmid = {30156531}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-flagellated, motile-by-gliding, orange-coloured bacterial strain, designated strain IMCC20180T, was isolated from seawater collected off the coast of the East Sea in the Republic of Korea. The 16S rRNA gene sequence analysis showed that strain IMCC20180T was most closely related to Winogradskyellaporiferorum UST030701-295T (95.7 % sequence similarity) and formed a robust phylogenetic clade with other Winogradskyella species, indicating that the strain was affiliated with the genus Winogradskyella. Growth of strain IMCC20180T was observed at 20-30 °C (optimum, 25 °C), pH 7.0-9.0 (pH 8.0) and with 1.0-3.5 % NaCl (3.0 %, w/v). The predominant isoprenoid quinone was MK-6. Major fatty acid constituents were iso-C15 : 1 G, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), iso-C15 : 0, iso-C17 : 0 3-OH and iso-C16 : 0 3-OH. The major polar lipids were phosphatidylethanolamine, four unknown aminolipids and five unknown lipids. The estimated genome size and the DNA G+C content of strain IMCC20180T were 3.1 Mb and 37.7 %, respectively. Based on 16S rRNA gene phylogeny, physiological and chemotaxonomic characterization, strain IMCC20180T represented a novel species in the genus Winogradskyella, for which the name Winogradskyellaaurantiaca sp. nov. is proposed. The type strain is IMCC20180T (=KACC 18883T=KCTC 52240T=JCM 31383T).}, } @article {pmid30156530, year = {2018}, author = {Deptula, P and Smolander, OP and Laine, P and Roberts, RJ and Edelmann, M and Peltola, P and Piironen, V and Paulin, L and Storgårds, E and Savijoki, K and Laitila, A and Auvinen, P and Varmanen, P}, title = {Acidipropionibacterium virtanenii sp. nov., isolated from malted barley.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3175-3183}, doi = {10.1099/ijsem.0.002965}, pmid = {30156530}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fermentation ; Finland ; Hordeum/*microbiology ; *Phylogeny ; Propionibacterium/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-positive, catalase-positive and pleomorphic rod organism was isolated from malted barley in Finland, classified initially by partial 16S rRNA gene sequencing and originally deposited in the VTT Culture Collection as a strain of Propionibacterium acidipropionici (currently Acidipropionibacterium acidipropionici). The subsequent comparison of the whole 16S rRNA gene with other representatives of the genus Acidipropionibacterium revealed that the strain belongs to a novel species, most closely related to Acidipropionibacterium microaerophilum and Acidipropionibacterium acidipropionici, with similarity values of 98.46 and 98.31 %, respectively. The whole genome sequencing using PacBio RS II platform allowed further comparison of the genome with all of the other DNA sequences available for the type strains of the Acidipropionibacterium species. Those comparisons revealed the highest similarity of strain JS278T to A. acidipropionici, which was confirmed by the average nucleotide identity analysis. The genome of strain JS278T is intermediate in size compared to the A. acidipropionici and Acidipropionibacterium jensenii at 3 432 872 bp, the G+C content is 68.4 mol%. The strain fermented a wide range of carbon sources, and produced propionic acid as the major fermentation product. Besides its poor ability to grow at 37 °C and positive catalase reaction, the observed phenotype was almost indistinguishable from those of A. acidipropionici and A. jensenii. Based on our findings, we conclude that the organism represents a novel member of the genus Acidipropionibacterium, for which we propose the name Acidipropionibacteriumvirtanenii sp. nov. The type strain is JS278T (=VTT E-113202T=DSM 106790T).}, } @article {pmid30156529, year = {2018}, author = {Liu, L and Hui, N and Liang, LX and Zhang, XX and Li, LB and Sun, QW}, title = {Sphingobacterium haloxyli sp. nov., an endophytic bacterium isolated from Haloxylon ammodendron stems in Kumtag desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3279-3284}, doi = {10.1099/ijsem.0.002982}, pmid = {30156529}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chenopodiaceae/*microbiology ; China ; DNA, Bacterial/genetics ; Desert Climate ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Stems/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sphingobacterium/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-motile, aerobic, non-spore-forming, rod-shaped, bacterial strain, designated 5JN-11T, was isolated from Haloxylonammodendron stems in Kumtag desert, Xinjiang province, China. Strain 5JN-11T grew at salinities of 0-6 % (w/v; optimum 0-2 %), a pH of 7.0-9.0 (pH 7.0-8.0) and temperatures of 20-42 °C (28-30 °C). Based on 16S rRNA gene sequences, the strain was designated a member of the genus Sphingobacterium and the phylogenetic analysis showed that strain 5JN-11T shared the highest similarity to Sphingobacterium gobiense H7T, followed by Sphingobacterium chuzhouense DH-5T and Sphingobacterium arenae H-12T. The unfinished draft genome of strain 5JN-11T was 4.69 Mb. The G+C content of strain 5JN-11T was 42.8 mol%. The average nucleotide identity to S. gobiense H7T was 90.5 %. The respiratory quinone was MK-7, and the major polar lipids were phosphatidylethanolamine and phosphoglycolipid. The predominant cellular fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 and iso-C17 : 0 3-OH. On the basis of phenotypic, genotypic and phylogenetic evidence, strain 5JN-11T represents a novel species in the genus Sphingobacterium, for which the name Sphingobacteriumhaloxyli sp. nov. is proposed. The type strain is 5JN-11T (=ACCC 60072T=KCTC 62457T).}, } @article {pmid30156528, year = {2018}, author = {Heo, J and Saitou, S and Tamura, T and Cho, H and Kim, JS and Joa, JH and Kim, JS and Kwon, SW and Kim, SJ}, title = {Lactobacilus nuruki sp. nov., isolated from Nuruk, a Korean fermentation starter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3273-3278}, doi = {10.1099/ijsem.0.002976}, pmid = {30156528}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fermented Foods/*microbiology ; *Food Microbiology ; Genes, Bacterial ; Glycolipids/chemistry ; Lactobacillus/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; }, abstract = {A rod-shaped, Gram-stain-positive, non-flagellated, facultatively anaerobic bacterium, designated SYF10-1aT, was isolated from Nuruk, a Korean traditional fermentation starter. It grew at 4-40 °C (optimum 37 °C), at pH 3.0-9.0 (optimum, pH 7.0) and with 0-5 % (w/v) NaCl. Phylogenetic analysis using 16S rRNA gene sequences revealed that strain SYF10-1aT belonged to the genus Lactobacillus and showed the highest sequence similarity of 98.7 % to Lactobacillus crustorum LMG 23699T. A comparison of two housekeeping genes, pheS and rpoA, supported the suggestion that strain SYF10-1aT fell within the radius of the genus Lactobacillus, but was clearly separated from its closest related species. The average nucleotide identity value and digital DNA-DNA hybridization value between strain SYF10-1aT and the most closely related species,L. crustorum LMG 23699T, were 80.5 and 33.3 %, respectively. The predominant cellular fatty acids were C16 : 0, C18 : 1ω9c, C18 : 1ω7c and summed feature 3 (including iso-C15 : 0 2-OH and/or C16 : 1ω7c). Polar lipids were diphosphatidylglycerol, phosphatidylglycerol, two unidentified aminolipids and two unidentified glycolipids. The cell-wall peptidoglycan was of the A4α type with an interpeptide bridge comprising l-Lys-d-Asp. The DNA G+C content was 34.2 mol%. On the basis of this taxonomic study, strain SYF10-1aT represents a novel species within the genus Lactobacillus, for which the name Lactobacillus nuruki sp. nov. is proposed. The type strain is SYF10-1aT (=KACC 18726T=NBRC 112011T).}, } @article {pmid30155671, year = {2018}, author = {Drehe, I and Simonetti, E and Ruiz, JA}, title = {Contribution of the Siderophores Pyoverdine and Enantio-Pyochelin to Fitness in Soil of Pseudomonas protegens Pf-5.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1560-1565}, pmid = {30155671}, issn = {1432-0991}, support = {UBACyT 20020130200117BA//Universidad de Buenos Aires (AR)/ ; }, mesh = {Fusaric Acid/metabolism ; Iron/metabolism ; Oligopeptides/*metabolism ; Phenols/*metabolism ; Pseudomonas/*metabolism ; Siderophores/*metabolism ; Soil ; Soil Microbiology ; Thiazoles/*metabolism ; }, abstract = {Pseudomonas protegens synthesizes two major iron-chelating metabolites (siderophores): pyoverdine (Pvd) and enantio-pyochelin (E-Pch). Although iron sequestration and uptake seem to be the main biological role of these siderophores, other functions including metal homeostasis and antibiotic activity have been proposed. The aim of this study was to evaluate the contribution of Pvd and E-Pch to the survival of P. protegens in soil using wild type and isogenic mutant strains unable to produce Pvd, E-Pch or both siderophores. Survival of these strains in sterile soil microcosms, in soil microcosms containing the native microflora and in sterile soil microcosms containing fusaric acid (a mycotoxin able to chelate iron and other metals), was compared by determination of colony forming units (CFU) per gram dry soil over time. In sterile soil, cell densities of Pvd-producing strains were significantly higher than that of non-producers after 21 days of permanence in the microcosms. In non-sterile soil, viability of all strains declined faster than in sterile soil and Pvd producers showed higher CFU × (g dry weight soil)-1 values than non-producers. The presence of fusaric acid negatively affected viability of strains unable to produce Pvd, while had no effect on the viability of strains able to produce Pvd. Altogether, these results show that the ability to produce Pvd increases survival of P. protegens in soil, while the ability to synthesize E-Pch does not, indicating that under the conditions which prevail in soil, iron scavenging via Pvd is more beneficial than via E-Pch.}, } @article {pmid30155670, year = {2018}, author = {Okuno, NT and Freire, IR and Segundo, RTRS and Silva, CR and Marin, VA}, title = {Polymerase Chain Reaction Assay for Detection of Stenotrophomonas maltophilia in Cheese Samples Based on the smeT Gene.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1555-1559}, pmid = {30155670}, issn = {1432-0991}, support = {1440268//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; }, mesh = {Animals ; Brazil ; Cattle ; Cheese/*microbiology ; Genes, Bacterial/*genetics ; Mastitis, Bovine/microbiology ; Milk/microbiology ; Polymerase Chain Reaction/methods ; RNA, Ribosomal/genetics ; Stenotrophomonas maltophilia/*genetics ; }, abstract = {Stenotrophomonas maltophilia is an emerging opportunistic pathogen linked not only to bacteremia, sepsis, and pneumonia but also to severe chronic enteritis. Persons with the impaired immune system are prone to be infected by S. maltophilia since its pathogenicity seems to be more associated with the host immune system than with the acquisition of specific virulence genes. In the dairy chain, S. maltophilia is linked to clinical and subclinical bovine mastitis in dairy cows, and it has been identified in cheese, and raw and pasteurized milk. There are reports of misidentification of S. maltophilia by commercial systems and PCR assays using primers based on the 23S rRNA and smeD genes, so the smeT gene is an alternative to identifying S. maltophilia by PCR due to its specificity to the S. maltophilia species. The present study reports an alternative species-specific PCR assay based on the smeT gene designed to identify S. maltophilia in cheese samples. We performed in silico and in vitro analyses to check the specificity of the primer pair. In silico analysis showed specificity of the primer pair to the species level. In vitro analysis was performed by testing the primer pair against pools of bacteria grown from 33 fresh Minas cheese samples acquired in the city of Rio de Janeiro, Brazil, without unspecific amplification.}, } @article {pmid30154544, year = {2018}, author = {Priyadarshini, S}, title = {India targets universities in predatory-journal crackdown.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {537-538}, doi = {10.1038/d41586-018-06048-2}, pmid = {30154544}, issn = {1476-4687}, mesh = {China ; Employee Performance Appraisal ; Faculty/statistics & numerical data ; India ; Motivation ; Periodicals as Topic/economics/*standards ; *Research Personnel/economics/statistics & numerical data ; Research Support as Topic ; Universities/*standards ; }, } @article {pmid30154543, year = {2018}, author = {Reardon, S}, title = {United States woefully unprepared for nuclear strike, say scientists.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {538-539}, doi = {10.1038/d41586-018-06077-x}, pmid = {30154543}, issn = {1476-4687}, } @article {pmid30154542, year = {2018}, author = {Moss, S}, title = {Research is set up for bullies to thrive.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {529}, doi = {10.1038/d41586-018-06040-w}, pmid = {30154542}, issn = {1476-4687}, mesh = {Bullying/*prevention & control/*psychology ; Female ; Humans ; Laboratories/organization & administration/standards ; Male ; Mentors/*psychology ; Research Personnel/*organization & administration/*psychology ; }, } @article {pmid30154541, year = {2018}, author = {Warren, M}, title = {Massive £30-million grant will be awarded to one cardiovascular research team.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {535-536}, doi = {10.1038/d41586-018-06068-y}, pmid = {30154541}, issn = {1476-4687}, mesh = {Awards and Prizes ; Biomedical Research/*economics ; *Cardiovascular System ; Financing, Organized/*economics ; Foundations/*economics ; Humans ; Internationality ; United Kingdom ; }, } @article {pmid30154539, year = {2018}, author = {Rosen, J}, title = {Help to shape policy with your science.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {671-673}, doi = {10.1038/d41586-018-06038-4}, pmid = {30154539}, issn = {1476-4687}, } @article {pmid30154536, year = {2018}, author = {Reardon, S}, title = {Trump's science-adviser pick hedges on climate change.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {536-537}, doi = {10.1038/d41586-018-06019-7}, pmid = {30154536}, issn = {1476-4687}, mesh = {*Climate Change ; *Federal Government ; Meteorology ; *Politics ; United States ; }, } @article {pmid30154535, year = {2018}, author = {Castelvecchi, D}, title = {Physicists doubt bold superconductivity claim following social-media storm.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {539-540}, doi = {10.1038/d41586-018-06023-x}, pmid = {30154535}, issn = {1476-4687}, } @article {pmid30154482, year = {2018}, author = {Burgess, DJ}, title = {Full speed ahead for single-cell analysis.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {668-669}, doi = {10.1038/s41576-018-0049-3}, pmid = {30154482}, issn = {1471-0064}, } @article {pmid30154238, year = {2018}, author = {Bourne, HR}, title = {Opinion: Expansion fever and soft money plague the biomedical research enterprise.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8647-8651}, pmid = {30154238}, issn = {1091-6490}, mesh = {Biomedical Research/*economics ; *Budgets ; Financing, Government/*economics ; Humans ; National Institutes of Health (U.S.)/*economics ; United States ; }, } @article {pmid30154170, year = {2018}, author = {Wang, D and Smith-Bell, CA and Burhans, LB and O'Dell, DE and Bell, RW and Schreurs, BG}, title = {Changes in membrane properties of rat deep cerebellar nuclear projection neurons during acquisition of eyeblink conditioning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9419-E9428}, pmid = {30154170}, issn = {1091-6490}, support = {P40 OD010996/OD/NIH HHS/United States ; R21 NS061103/NS/NINDS NIH HHS/United States ; R21 NS094009/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Blinking ; *Cell Membrane ; Cerebellar Nuclei/*physiopathology ; Electric Stimulation ; Herpesvirus 1, Suid ; *Neurons ; Pseudorabies/physiopathology ; Rats ; Rats, Long-Evans ; }, abstract = {Previous studies have shown changes in membrane properties of neurons in rat deep cerebellar nuclei (DCN) as a function of development, but due to technical difficulties in obtaining viable DCN slices from adult animals, it remains unclear whether there are learning-related alterations in the membrane properties of DCN neurons in adult rats. This study was designed to record from identified DCN cells in cerebellar slices from postnatal day 25-26 (P25-26) rats that had a relatively mature sensory nervous system and were able to acquire learning as a result of tone-shock eyeblink conditioning (EBC) and to document resulting changes in electrophysiological properties. After electromyographic electrode implantation at P21 and inoculation with a fluorescent pseudorabies virus (PRV-152) at P22-23, rats received either four sessions of paired delay EBC or unpaired stimulus presentations with a tone conditioned stimulus and a shock unconditioned stimulus or sat in the training chamber without stimulus presentations. Compared with rats given unpaired stimuli or no stimulus presentations, rats given paired EBC showed an increase in conditioned responses across sessions. Whole-cell recordings of both fluorescent and nonfluorescent DCN projection neurons showed that delay EBC induced significant changes in membrane properties of evoked DCN action potentials including a reduced after-hyperpolarization amplitude and shortened latency. Similar findings were obtained in hyperpolarization-induced rebound spikes of DCN neurons. In sum, delay EBC produced significant changes in the membrane properties of juvenile rat DCN projection neurons. These learning-specific changes in DCN excitability have not previously been reported in any species or task.}, } @article {pmid30154169, year = {2018}, author = {Hansen, LP and Miao, J}, title = {Aversion to ambiguity and model misspecification in dynamic stochastic environments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9163-9168}, doi = {10.1073/pnas.1811243115}, pmid = {30154169}, issn = {1091-6490}, abstract = {Preferences that accommodate aversion to subjective uncertainty and its potential misspecification in dynamic settings are a valuable tool of analysis in many disciplines. By generalizing previous analyses, we propose a tractable approach to incorporating broadly conceived responses to uncertainty. We illustrate our approach on some stylized stochastic environments. By design, these discrete time environments have revealing continuous time limits. Drawing on these illustrations, we construct recursive representations of intertemporal preferences that allow for penalized and smooth ambiguity aversion to subjective uncertainty. These recursive representations imply continuous time limiting Hamilton-Jacobi-Bellman equations for solving control problems in the presence of uncertainty.}, } @article {pmid30154168, year = {2018}, author = {Bail, CA and Argyle, LP and Brown, TW and Bumpus, JP and Chen, H and Hunzaker, MBF and Lee, J and Mann, M and Merhout, F and Volfovsky, A}, title = {Exposure to opposing views on social media can increase political polarization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9216-9221}, pmid = {30154168}, issn = {1091-6490}, mesh = {*Democracy ; Female ; Humans ; Male ; *Political Activism ; *Social Media ; United States ; }, abstract = {There is mounting concern that social media sites contribute to political polarization by creating "echo chambers" that insulate people from opposing views about current events. We surveyed a large sample of Democrats and Republicans who visit Twitter at least three times each week about a range of social policy issues. One week later, we randomly assigned respondents to a treatment condition in which they were offered financial incentives to follow a Twitter bot for 1 month that exposed them to messages from those with opposing political ideologies (e.g., elected officials, opinion leaders, media organizations, and nonprofit groups). Respondents were resurveyed at the end of the month to measure the effect of this treatment, and at regular intervals throughout the study period to monitor treatment compliance. We find that Republicans who followed a liberal Twitter bot became substantially more conservative posttreatment. Democrats exhibited slight increases in liberal attitudes after following a conservative Twitter bot, although these effects are not statistically significant. Notwithstanding important limitations of our study, these findings have significant implications for the interdisciplinary literature on political polarization and the emerging field of computational social science.}, } @article {pmid30154167, year = {2018}, author = {Stolzenburg, D and Fischer, L and Vogel, AL and Heinritzi, M and Schervish, M and Simon, M and Wagner, AC and Dada, L and Ahonen, LR and Amorim, A and Baccarini, A and Bauer, PS and Baumgartner, B and Bergen, A and Bianchi, F and Breitenlechner, M and Brilke, S and Buenrostro Mazon, S and Chen, D and Dias, A and Draper, DC and Duplissy, J and El Haddad, I and Finkenzeller, H and Frege, C and Fuchs, C and Garmash, O and Gordon, H and He, X and Helm, J and Hofbauer, V and Hoyle, CR and Kim, C and Kirkby, J and Kontkanen, J and Kürten, A and Lampilahti, J and Lawler, M and Lehtipalo, K and Leiminger, M and Mai, H and Mathot, S and Mentler, B and Molteni, U and Nie, W and Nieminen, T and Nowak, JB and Ojdanic, A and Onnela, A and Passananti, M and Petäjä, T and Quéléver, LLJ and Rissanen, MP and Sarnela, N and Schallhart, S and Tauber, C and Tomé, A and Wagner, R and Wang, M and Weitz, L and Wimmer, D and Xiao, M and Yan, C and Ye, P and Zha, Q and Baltensperger, U and Curtius, J and Dommen, J and Flagan, RC and Kulmala, M and Smith, JN and Worsnop, DR and Hansel, A and Donahue, NM and Winkler, PM}, title = {Rapid growth of organic aerosol nanoparticles over a wide tropospheric temperature range.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9122-9127}, pmid = {30154167}, issn = {1091-6490}, abstract = {Nucleation and growth of aerosol particles from atmospheric vapors constitutes a major source of global cloud condensation nuclei (CCN). The fraction of newly formed particles that reaches CCN sizes is highly sensitive to particle growth rates, especially for particle sizes <10 nm, where coagulation losses to larger aerosol particles are greatest. Recent results show that some oxidation products from biogenic volatile organic compounds are major contributors to particle formation and initial growth. However, whether oxidized organics contribute to particle growth over the broad span of tropospheric temperatures remains an open question, and quantitative mass balance for organic growth has yet to be demonstrated at any temperature. Here, in experiments performed under atmospheric conditions in the Cosmics Leaving Outdoor Droplets (CLOUD) chamber at the European Organization for Nuclear Research (CERN), we show that rapid growth of organic particles occurs over the range from [Formula: see text]C to [Formula: see text]C. The lower extent of autoxidation at reduced temperatures is compensated by the decreased volatility of all oxidized molecules. This is confirmed by particle-phase composition measurements, showing enhanced uptake of relatively less oxygenated products at cold temperatures. We can reproduce the measured growth rates using an aerosol growth model based entirely on the experimentally measured gas-phase spectra of oxidized organic molecules obtained from two complementary mass spectrometers. We show that the growth rates are sensitive to particle curvature, explaining widespread atmospheric observations that particle growth rates increase in the single-digit-nanometer size range. Our results demonstrate that organic vapors can contribute to particle growth over a wide range of tropospheric temperatures from molecular cluster sizes onward.}, } @article {pmid30154166, year = {2018}, author = {Millereau, P and Ducrot, E and Clough, JM and Wiseman, ME and Brown, HR and Sijbesma, RP and Creton, C}, title = {Mechanics of elastomeric molecular composites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9110-9115}, pmid = {30154166}, issn = {1091-6490}, abstract = {A classic paradigm of soft and extensible polymer materials is the difficulty of combining reversible elasticity with high fracture toughness, in particular for moduli above 1 MPa. Our recent discovery of multiple network acrylic elastomers opened a pathway to obtain precisely such a combination. We show here that they can be seen as true molecular composites with a well-cross-linked network acting as a percolating filler embedded in an extensible matrix, so that the stress-strain curves of a family of molecular composite materials made with different volume fractions of the same cross-linked network can be renormalized into a master curve. For low volume fractions (<3%) of cross-linked network, we demonstrate with mechanoluminescence experiments that the elastomer undergoes a strong localized softening due to scission of covalent bonds followed by a stable necking process, a phenomenon never observed before in elastomers. The quantification of the emitted luminescence shows that the damage in the material occurs in two steps, with a first step where random bond breakage occurs in the material accompanied by a moderate level of dissipated energy and a second step where a moderate level of more localized bond scission leads to a much larger level of dissipated energy. This combined use of mechanical macroscopic testing and molecular bond scission data provides unprecedented insight on how tough soft materials can damage and fail.}, } @article {pmid30154165, year = {2018}, author = {Shekhar, C and Kumar, N and Grinenko, V and Singh, S and Sarkar, R and Luetkens, H and Wu, SC and Zhang, Y and Komarek, AC and Kampert, E and Skourski, Y and Wosnitza, J and Schnelle, W and McCollam, A and Zeitler, U and Kübler, J and Yan, B and Klauss, HH and Parkin, SSP and Felser, C}, title = {Anomalous Hall effect in Weyl semimetal half-Heusler compounds RPtBi (R = Gd and Nd).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9140-9144}, pmid = {30154165}, issn = {1091-6490}, abstract = {Topological materials ranging from topological insulators to Weyl and Dirac semimetals form one of the most exciting current fields in condensed-matter research. Many half-Heusler compounds, RPtBi (R = rare earth), have been theoretically predicted to be topological semimetals. Among various topological attributes envisaged in RPtBi, topological surface states, chiral anomaly, and planar Hall effect have been observed experimentally. Here, we report an unusual intrinsic anomalous Hall effect (AHE) in the antiferromagnetic Heusler Weyl semimetal compounds GdPtBi and NdPtBi that is observed over a wide temperature range. In particular, GdPtBi exhibits an anomalous Hall conductivity of up to 60 Ω-1⋅cm-1 and an anomalous Hall angle as large as 23%. Muon spin-resonance (μSR) studies of GdPtBi indicate a sharp antiferromagnetic transition (TN) at 9 K without any noticeable magnetic correlations above TN Our studies indicate that Weyl points in these half-Heuslers are induced by a magnetic field via exchange splitting of the electronic bands at or near the Fermi energy, which is the source of the chiral anomaly and the AHE.}, } @article {pmid30154164, year = {2018}, author = {Sapountzis, P and Paneri, S and Gregoriou, GG}, title = {Distinct roles of prefrontal and parietal areas in the encoding of attentional priority.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8755-E8764}, pmid = {30154164}, issn = {1091-6490}, mesh = {Animals ; Attention/*physiology ; Brain Mapping ; Female ; Frontal Lobe/*physiology ; Macaca mulatta ; Neurons/physiology ; Parietal Lobe/*physiology ; Photic Stimulation ; Prefrontal Cortex/*physiology ; Saccades/physiology ; Visual Fields/physiology ; }, abstract = {When searching for an object in a crowded scene, information about the similarity of stimuli to the target object is thought to be encoded in spatial priority maps, which are subsequently used to guide shifts of attention and gaze to likely targets. Two key cortical areas that have been described as holding priority maps are the frontal eye field (FEF) and the lateral intraparietal area (LIP). However, little is known about their distinct contributions in priority encoding. Here, we compared neuronal responses in FEF and LIP during free-viewing visual search. Although saccade selection signals emerged earlier in FEF, information about the target emerged at similar latencies in distinct populations within the two areas. Notably, however, effects in FEF were more pronounced. Moreover, LIP neurons encoded the similarity of stimuli to the target independent of saccade selection, whereas in FEF, encoding of target similarity was strongly modulated by saccade selection. Taken together, our findings suggest hierarchical processing of saccade selection signals and parallel processing of feature-based attention signals within the parietofrontal network with FEF having a more prominent role in priority encoding. Furthermore, they suggest discrete roles of FEF and LIP in the construction of priority maps.}, } @article {pmid30154163, year = {2018}, author = {Zhang, S and Tao, F and Qing, R and Tang, H and Skuhersky, M and Corin, K and Tegler, L and Wassie, A and Wassie, B and Kwon, Y and Suter, B and Entzian, C and Schubert, T and Yang, G and Labahn, J and Kubicek, J and Maertens, B}, title = {QTY code enables design of detergent-free chemokine receptors that retain ligand-binding activities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8652-E8659}, pmid = {30154163}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Amino Acid Substitution ; Amino Acids/chemistry/genetics/metabolism ; Detergents/chemistry ; Glutamine/chemistry/genetics/*metabolism ; Hot Temperature ; Humans ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Protein Binding ; Protein Stability ; Protein Structure, Secondary ; Receptors, Chemokine/chemistry/genetics/*metabolism ; Solubility ; Threonine/chemistry/genetics/*metabolism ; Tyrosine/chemistry/genetics/*metabolism ; Water/chemistry ; }, abstract = {Structure and function studies of membrane proteins, particularly G protein-coupled receptors and multipass transmembrane proteins, require detergents. We have devised a simple tool, the QTY code (glutamine, threonine, and tyrosine), for designing hydrophobic domains to become water soluble without detergents. Here we report using the QTY code to systematically replace the hydrophobic amino acids leucine, valine, isoleucine, and phenylalanine in the seven transmembrane α-helices of CCR5, CXCR4, CCR10, and CXCR7. We show that QTY code-designed chemokine receptor variants retain their thermostabilities, α-helical structures, and ligand-binding activities in buffer and 50% human serum. CCR5QTY, CXCR4QTY, and CXCR7QTY also bind to HIV coat protein gp41-120. Despite substantial transmembrane domain changes, the detergent-free QTY variants maintain stable structures and retain their ligand-binding activities. We believe the QTY code will be useful for designing water-soluble variants of membrane proteins and other water-insoluble aggregated proteins.}, } @article {pmid30154162, year = {2018}, author = {Zimmer, B and Ewaleifoh, O and Harschnitz, O and Lee, YS and Peneau, C and McAlpine, JL and Liu, B and Tchieu, J and Steinbeck, JA and Lafaille, F and Volpi, S and Notarangelo, LD and Casanova, JL and Zhang, SY and Smith, GA and Studer, L}, title = {Human iPSC-derived trigeminal neurons lack constitutive TLR3-dependent immunity that protects cortical neurons from HSV-1 infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8775-E8782}, pmid = {30154162}, issn = {1091-6490}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 NS072381/NS/NINDS NIH HHS/United States ; R21 NS084255/NS/NINDS NIH HHS/United States ; UL1 TR001866/TR/NCATS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Antiviral Agents/pharmacology ; Cell Differentiation/genetics ; Cells, Cultured ; Cerebral Cortex/cytology ; Child ; Herpesvirus 1, Human/immunology/physiology ; Humans ; Immunity/genetics/*immunology ; Induced Pluripotent Stem Cells/cytology/*metabolism ; Interferon-beta/pharmacology ; Mutation ; Neurons/drug effects/*metabolism/virology ; Poly I-C/pharmacology ; Toll-Like Receptor 3/genetics/*metabolism ; Trigeminal Ganglion/cytology ; }, abstract = {Herpes simplex virus type 1 (HSV-1) encephalitis (HSE) is the most common sporadic viral encephalitis in Western countries. Some HSE children carry inborn errors of the Toll-like receptor 3 (TLR3)-dependent IFN-α/β- and -λ-inducing pathway. Induced pluripotent stem cell (iPSC)-derived cortical neurons with TLR3 pathway mutations are highly susceptible to HSV-1, due to impairment of cell-intrinsic TLR3-IFN immunity. In contrast, the contribution of cell-intrinsic immunity of human trigeminal ganglion (TG) neurons remains unclear. Here, we describe efficient in vitro derivation and purification of TG neurons from human iPSCs via a cranial placode intermediate. The resulting TG neurons are of sensory identity and exhibit robust responses to heat (capsaicin), cold (icilin), and inflammatory pain (ATP). Unlike control cortical neurons, both control and TLR3-deficient TG neurons were highly susceptible to HSV-1. However, pretreatment of control TG neurons with poly(I:C) induced the cells into an anti-HSV-1 state. Moreover, both control and TLR3-deficient TG neurons developed resistance to HSV-1 following pretreatment with IFN-β but not IFN-λ. These data indicate that TG neurons are vulnerable to HSV-1 because they require preemptive stimulation of the TLR3 or IFN-α/β receptors to induce antiviral immunity, whereas cortical neurons possess a TLR3-dependent constitutive resistance that is sufficient to block incoming HSV-1 in the absence of prior antiviral signals. The lack of constitutive resistance in TG neurons in vitro is consistent with their exploitation as a latent virus reservoir in vivo. Our results incriminate deficiencies in the constitutive TLR3-dependent response of cortical neurons in the pathogenesis of HSE.}, } @article {pmid30154161, year = {2018}, author = {Vainik, U and Baker, TE and Dadar, M and Zeighami, Y and Michaud, A and Zhang, Y and García Alanis, JC and Misic, B and Collins, DL and Dagher, A}, title = {Neurobehavioral correlates of obesity are largely heritable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9312-9317}, pmid = {30154161}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {*Body Mass Index ; *Brain/physiology/physiopathology ; *Cognition ; *Feeding Behavior ; Female ; Humans ; Male ; *Obesity/genetics/pathology/physiopathology ; }, abstract = {Recent molecular genetic studies have shown that the majority of genes associated with obesity are expressed in the central nervous system. Obesity has also been associated with neurobehavioral factors such as brain morphology, cognitive performance, and personality. Here, we tested whether these neurobehavioral factors were associated with the heritable variance in obesity measured by body mass index (BMI) in the Human Connectome Project (n = 895 siblings). Phenotypically, cortical thickness findings supported the "right brain hypothesis" for obesity. Namely, increased BMI is associated with decreased cortical thickness in right frontal lobe and increased thickness in the left frontal lobe, notably in lateral prefrontal cortex. In addition, lower thickness and volume in entorhinal-parahippocampal structures and increased thickness in parietal-occipital structures in participants with higher BMI supported the role of visuospatial function in obesity. Brain morphometry results were supported by cognitive tests, which outlined a negative association between BMI and visuospatial function, verbal episodic memory, impulsivity, and cognitive flexibility. Personality-BMI correlations were inconsistent. We then aggregated the effects for each neurobehavioral factor for a behavioral genetics analysis and estimated each factor's genetic overlap with BMI. Cognitive test scores and brain morphometry had 0.25-0.45 genetic correlations with BMI, and the phenotypic correlations with BMI were 77-89% explained by genetic factors. Neurobehavioral factors also had some genetic overlap with each other. In summary, obesity as measured by BMI has considerable genetic overlap with brain and cognitive measures. This supports the theory that obesity is inherited via brain function and may inform intervention strategies.}, } @article {pmid30154160, year = {2018}, author = {Chen, C and Goldman, DP and Zissimopoulos, J and Rowe, JW and , }, title = {Multidimensional comparison of countries' adaptation to societal aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9169-9174}, pmid = {30154160}, issn = {1091-6490}, mesh = {*Aging ; Humans ; Japan ; *Life Expectancy ; Netherlands ; *Social Change ; *Social Conditions ; United States ; }, abstract = {As long-term changes in life expectancy and fertility drive the emergence of aging societies across the globe, individual countries vary widely in the development of age-relevant policies and programs. While failure to adapt to the demographic transformation carries not only important financial risks but also social risks, most efforts to gauge countries' preparedness focus on economic indicators. Using data from the Organization for Economic Cooperation and Development (OECD) and other sources, we developed a multidimensional Aging Society Index that assesses the status of older populations across five specific domains, including productivity and engagement, well-being, equity, economic and physical security, and intergenerational cohesion. For 18 OECD countries, the results demonstrate substantial diversity in countries' progress in adapting to aging. For any given domain, there are wide differences across countries, and within most countries, there is substantial variation across domains. Overall, Norway and Sweden rank first in adaptation to aging, followed by the United States, The Netherlands, and Japan. Central and eastern European countries rank at the bottom, with huge untapped potential for successful aging. The United States ranks best in productivity and engagement, in the top half for cohesion, and in the middle in well-being, but it ranks third from the bottom in equity. Only well-being and security showed significant between-domain correlation (r = 0.59, P = 0.011), strengthening the case for a multidimensional index. Examination of heterogeneity within and across domains of the index can be used to assess the need for, and effectiveness of, various programs and policies and facilitate successful adaptation to the demographic transition.}, } @article {pmid30154159, year = {2018}, author = {Nummenmaa, L and Hari, R and Hietanen, JK and Glerean, E}, title = {Maps of subjective feelings.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9198-9203}, pmid = {30154159}, issn = {1091-6490}, support = {313000//European Research Council/International ; }, mesh = {Adult ; *Cognition ; *Databases, Factual ; *Emotions ; Female ; Humans ; Male ; *Sensation ; }, abstract = {Subjective feelings are a central feature of human life. We defined the organization and determinants of a feeling space involving 100 core feelings that ranged from cognitive and affective processes to somatic sensations and common illnesses. The feeling space was determined by a combination of basic dimension rating, similarity mapping, bodily sensation mapping, and neuroimaging meta-analysis. A total of 1,026 participants took part in online surveys where we assessed (i) for each feeling, the intensity of four hypothesized basic dimensions (mental experience, bodily sensation, emotion, and controllability), (ii) subjectively experienced similarity of the 100 feelings, and (iii) topography of bodily sensations associated with each feeling. Neural similarity between a subset of the feeling states was derived from the NeuroSynth meta-analysis database based on the data from 9,821 brain-imaging studies. All feelings were emotionally valenced and the saliency of bodily sensations correlated with the saliency of mental experiences associated with each feeling. Nonlinear dimensionality reduction revealed five feeling clusters: positive emotions, negative emotions, cognitive processes, somatic states and illnesses, and homeostatic states. Organization of the feeling space was best explained by basic dimensions of emotional valence, mental experiences, and bodily sensations. Subjectively felt similarity of feelings was associated with basic feeling dimensions and the topography of the corresponding bodily sensations. These findings reveal a map of subjective feelings that are categorical, emotional, and embodied.}, } @article {pmid30153945, year = {2018}, author = {Du, A and Alemseged, Z}, title = {Diversity analysis of Plio-Pleistocene large mammal communities in the Omo-Turkana Basin, eastern Africa.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {25-39}, doi = {10.1016/j.jhevol.2018.07.004}, pmid = {30153945}, issn = {1095-8606}, abstract = {Knowing how the diversity of large mammal communities changes across space and time provides an important ecological framework for studying hominin evolution. However, diversity studies that apply methods currently used by neoecologists are rare in paleoanthropology and are also challenging due to diversity's unusual statistical properties. Here, we apply up-to-date analytical methods for understanding how species- and genus-level large mammalian diversity in the Omo-Turkana Basin changed through time and across space at multiple spatiotemporal scales (within each formation:102-3 km2 and 104-5 years; and within the basin as a whole: 103 km2 and 105 years). We found that, on average, Koobi Fora's large mammal community was more diverse than Nachukui's, which in turn was more diverse than Shungura's. Diversity was stable through time within each of these formations (alpha diversity), as was diversity in the basin as a whole (gamma diversity). Compositional dissimilarity between these three formations (beta diversity) was relatively low through time, with a 0.6 average proportion of shared species, suggesting dispersal acted to homogenize the region. Though alpha and gamma diversity were fairly stable through time, we do observe several notable peaks: during the KBS Member in Koobi Fora (30% increase), the Lokalalei Member in Nachukui (120% increase), and at 1.7 Ma in the entire basin (100% increase). We conclude by (1) demonstrating that habitat heterogeneity was an important factor influencing alpha diversity within each of the three formations, and (2) hypothesizing that diversity stability may have been driven by equilibrial dynamics in which overall diversity was constrained by resource availability, implying biotic interactions were an important factor in structuring the communities that included hominins as members. Our findings demonstrate the need to quantify how large mammal diversity changes across time and space in order to further our understanding of hominin ecology and evolution.}, } @article {pmid30153867, year = {2018}, author = {Adjei, EF and Adiku, TK and Mawuli, G and Bonney, JHK}, title = {Molecular investigations of viral meningitis among HIV-infected adults in Accra, Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {615}, pmid = {30153867}, issn = {1756-0500}, support = {EC/ORID/01//Government of Ghana through a grant support from the University of Ghana Research Fund./ ; }, mesh = {Adult ; Enterovirus/genetics/isolation & purification ; Ghana ; HIV Infections/*complications ; Humans ; Meningitis, Viral/complications/*virology ; Real-Time Polymerase Chain Reaction ; }, abstract = {OBJECTIVE: Meningitis is one of the leading causes of death among patients living with the human immunodeficiency virus (HIV) in sub-Saharan Africa. Based on clinical presentations alone, the different types of meningitis may not be distinguished from each other, consequently accurate laboratory diagnosis is extremely essential. Viruses such as Enteroviruses (EV), Mumps virus (MuV) and Herpes Simplex Virus-1 (HSV-1) are implicated in cases of meningitis. We sought to detect and characterize viral aetiologies of meningitis among HIV-infected adults with the use of molecular tools.

RESULTS: As a subset of a main research work, cerebrospinal fluid specimens were collected from a cross-section of HIV patients at the Fevers Unit of the Korle Bu Teaching Hospital with clinical features suggestive of meningitis but without laboratory confirmation. Laboratory investigations were performed with the use of the real time polymerase chain reaction for pan EV, MuV and HSV-1. None of the viruses investigated in this study was found to be positive for meningitis. However, lymphocytic pleocytosis, normal glucose and elevated protein levels were observed in some of the study participants.}, } @article {pmid30153861, year = {2018}, author = {Mangrio, E and Carlson, E and Zdravkovic, S}, title = {Understanding experiences of the Swedish health care system from the perspective of newly arrived refugees.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {616}, pmid = {30153861}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Delivery of Health Care ; Emigrants and Immigrants ; Female ; *Health Services Accessibility ; Humans ; Male ; Middle Aged ; Qualitative Research ; *Refugees ; Sweden ; Young Adult ; }, abstract = {OBJECTIVE: Refugees seek medical advice for a variety of reasons. Previous research suggests that understanding the refugees' experiences of and access to healthcare are important factors for improving their health as access to healthcare has been found to be a leading health indicator. Therefore, the aim of this study was to illuminate experiences of the Swedish health care system from the perspective of newly arrived refugees.

RESULTS: More than 70% of newly arrived refugees in the county of Scania were in need of health care during the last 3 months of 2015-2016. They did not seek care to the same extent as the general population. The main reasons were explained as too high costs, long waiting times and language difficulties. Some disclosed being denied access to health care for reasons, such as being denied care when seeking emergency room for stomach problems and being denied follow-up care for diabetes.}, } @article {pmid30153857, year = {2018}, author = {Ugarte, A and Vicedomini, R and Bernardes, J and Carbone, A}, title = {A multi-source domain annotation pipeline for quantitative metagenomic and metatranscriptomic functional profiling.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {149}, pmid = {30153857}, issn = {2049-2618}, abstract = {BACKGROUND: Biochemical and regulatory pathways have until recently been thought and modelled within one cell type, one organism and one species. This vision is being dramatically changed by the advent of whole microbiome sequencing studies, revealing the role of symbiotic microbial populations in fundamental biochemical functions. The new landscape we face requires the reconstruction of biochemical and regulatory pathways at the community level in a given environment. In order to understand how environmental factors affect the genetic material and the dynamics of the expression from one environment to another, we want to evaluate the quantity of gene protein sequences or transcripts associated to a given pathway by precisely estimating the abundance of protein domains, their weak presence or absence in environmental samples.

RESULTS: MetaCLADE is a novel profile-based domain annotation pipeline based on a multi-source domain annotation strategy. It applies directly to reads and improves identification of the catalog of functions in microbiomes. MetaCLADE is applied to simulated data and to more than ten metagenomic and metatranscriptomic datasets from different environments where it outperforms InterProScan in the number of annotated domains. It is compared to the state-of-the-art non-profile-based and profile-based methods, UProC and HMM-GRASPx, showing complementary predictions to UProC. A combination of MetaCLADE and UProC improves even further the functional annotation of environmental samples.

CONCLUSIONS: Learning about the functional activity of environmental microbial communities is a crucial step to understand microbial interactions and large-scale environmental impact. MetaCLADE has been explicitly designed for metagenomic and metatranscriptomic data and allows for the discovery of patterns in divergent sequences, thanks to its multi-source strategy. MetaCLADE highly improves current domain annotation methods and reaches a fine degree of accuracy in annotation of very different environments such as soil and marine ecosystems, ancient metagenomes and human tissues.}, } @article {pmid30153818, year = {2018}, author = {Li, C and Li, Y and Zhou, G and Gao, Y and Ma, S and Chen, Y and Song, J and Wang, X}, title = {Whole-genome bisulfite sequencing of goat skins identifies signatures associated with hair cycling.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {638}, pmid = {30153818}, issn = {1471-2164}, support = {31402038, 31372279//National Natural Science Foundation of China/ ; 31772571//National Natural Science Foundation of China/ ; 2014M560810, 2015T81059//China Postdoctoral Science Foundation/ ; CARS-39//China Agro-industry Research System/ ; }, mesh = {Animals ; DNA Methylation ; Epigenesis, Genetic ; *Genomics ; *Goats ; Hair Follicle/*growth & development ; Seasons ; *Sequence Analysis, DNA ; Skin/*metabolism ; Sulfites/*pharmacology ; }, abstract = {BACKGROUND: Hair follicles (HFs), upon development, undergo repetitive cycles of growth (anagen), regression (catagen), and rest (telogen). The transition between the stages is determined by multiple molecular signals, including DNA methylation, which plays important roles in mammalian cellular identity and is essential for the development of HFs. Secondary hair follicles (SHFs) in cashmere goat exhibit classic cyclic hair development, and little has been done on a genome-wide scale to examine potentially methylated genes involved in the hair cyclic transition.

RESULTS: Genome-wide DNA methylation profiles between skin tissues sampled during the anagen and telogen stages in cashmere goats were investigated using whole-genome bisulfite sequencing (WGBS). The methylation status was observed to be higher in the skin samples with HFs in the telogen than those in the anagen stage. A total of 1311 differentially methylated regions (DMRs) were identified between the two groups, which contained 493 fully annotated DMR-related genes (DMGs) (269 Hyper- DMGs and 224 Hypo-DMGs). Furthermore, a significant over-representation of the functional categories for DMGs related to immune response and intercellular crosstalk during hair cycling was observed. By integrating DNA methylation and mRNA expression data, we revealed that four genes (FMN1, PCOLCE, SPTLC3, and COL5A1) are crucial factors for elucidating epigenetic mechanisms contributing to the telogen-to-anagen transition.

CONCLUSION: Our study provided systematic methylome maps pertaining to the hair cycling stages (anagen vs telogen) at a single-base resolution, and revealed stage-specific methylation loci during cashmere growth or quiescence. Furthermore, we identified epigenetically regulated genes that are potentially involved in HF development and growth in cashmere goats, and likely in other mammal species.}, } @article {pmid30153812, year = {2018}, author = {Bhuiyan, SA and Ly, S and Phan, M and Huntington, B and Hogan, E and Liu, CC and Liu, J and Pavlidis, P}, title = {Systematic evaluation of isoform function in literature reports of alternative splicing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {637}, pmid = {30153812}, issn = {1471-2164}, support = {R01 MH111099/MH/NIMH NIH HHS/United States ; CREATE//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2016-05991//Natural Sciences and Engineering Research Council of Canada (CA)/ ; MH111099//National Institute of Mental Health/ ; }, mesh = {*Alternative Splicing ; Animals ; *Computational Biology ; Humans ; Mice ; Protein Isoforms/*genetics ; }, abstract = {BACKGROUND: Although most genes in mammalian genomes have multiple isoforms, an ongoing debate is whether these isoforms are all functional as well as the extent to which they increase the functional repertoire of the genome. To ground this debate in data, it would be helpful to have a corpus of experimentally-verified cases of genes which have functionally distinct splice isoforms (FDSIs).

RESULTS: We established a curation framework for evaluating experimental evidence of FDSIs, and analyzed over 700 human and mouse genes, strongly biased towards genes that are prominent in the alternative splicing literature. Despite this bias, we found experimental evidence meeting the classical definition for functionally distinct isoforms for ~ 5% of the curated genes. If we relax our criteria for inclusion to include weaker forms of evidence, the fraction of genes with evidence of FDSIs remains low (~ 13%). We provide evidence that this picture will not change substantially with further curation and conclude there is a large gap between the presumed impact of splicing on gene function and the experimental evidence. Furthermore, many functionally distinct isoforms were not traceable to a specific isoform in Ensembl, a database that forms the basis for much computational research.

CONCLUSIONS: We conclude that the claim that alternative splicing vastly increases the functional repertoire of the genome is an extrapolation from a limited number of empirically supported cases. We also conclude that more work is needed to integrate experimental evidence and genome annotation databases. Our work should help shape research around the role of splicing on gene function from presuming large general effects to acknowledging the need for stronger experimental evidence.}, } @article {pmid30153810, year = {2018}, author = {Larriba, E and Rial, E and Del Mazo, J}, title = {The landscape of mitochondrial small non-coding RNAs in the PGCs of male mice, spermatogonia, gametes and in zygotes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {634}, pmid = {30153810}, issn = {1471-2164}, support = {TC0000100//Unit of Information Resources for Research (URICI)/ ; }, mesh = {3T3-L1 Cells ; Animals ; Cell Differentiation ; Germ Cells/*metabolism ; Male ; Mice ; MicroRNAs/genetics ; Mitochondria/*genetics ; RNA, Small Interfering/genetics ; RNA, Small Untranslated/*genetics ; Spermatogonia/*cytology/metabolism ; }, abstract = {BACKGROUND: Mitochondria are organelles that fulfill a fundamental role in cell bioenergetics, as well as in other processes like cell signaling and death. Small non-coding RNAs (sncRNA) are now being considered as pivotal post-transcriptional regulators, widening the landscape of their diversity and functions. In mammalian cells, small RNAs encoded by the mitochondrial genome, mitosRNAs were discovered recently, although their biological role remains uncertain.

RESULTS: Here, using specific bioinformatics analyses, we have defined the diversity of mitosRNAs present in early differentiated germ cells of male mice (PGCs and spermatogonia), and in the gametes of both sexes and in zygotes. We found strong transcription of mitosRNAs relative to the size of the mtDNA, and classifying these mitosRNAs into different functional sncRNA groups highlighted the predominance of Piwi-interacting RNAs (piRNAs) relative to the other types of mitosRNAs. Mito-piRNAs were more abundant in oocytes and zygotes, where mitochondria fulfill key roles in fecundation process. Functional analysis of some particular mito-piRNAs (mito-piR-7,456,245), also expressed in 3T3-L1 cells, was assessed after exposure to RNA antagonists.

CONCLUSIONS: As far as we are aware, this is the first integrated analysis of sncRNAs encoded by mtDNA in germ cells and zygotes. The data obtained suggesting that mitosRNAs fulfill key roles in gamete differentiation and fertilization.}, } @article {pmid30153801, year = {2018}, author = {Lu, Y and Baras, AS and Halushka, MK}, title = {miRge 2.0 for comprehensive analysis of microRNA sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {275}, pmid = {30153801}, issn = {1471-2105}, support = {R01 HL137811/HL/NHLBI NIH HHS/United States ; 1R01HL137811//National Heart, Lung, and Blood Institute/ ; 17GRNT33670405//American Heart Association/ ; }, mesh = {Animals ; Computational Biology/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mice ; MicroRNAs/*genetics ; Phylogeny ; Rats ; Sequence Analysis, RNA/*methods ; *Software ; }, abstract = {BACKGROUND: miRNAs play important roles in the regulation of gene expression. The rapidly developing field of microRNA sequencing (miRNA-seq; small RNA-seq) needs comprehensive, robust, user-friendly and standardized bioinformatics tools to analyze these large datasets. We present miRge 2.0, in which multiple enhancements were made towards these goals.

RESULTS: miRge 2.0 has become more comprehensive with increased functionality including a novel miRNA detection method, A-to-I editing analysis, integrated standardized GFF3 isomiR reporting, and improved alignment to miRNAs. The novel miRNA detection method uniquely uses both miRNA hairpin sequence structure and composition of isomiRs resulting in higher specificity for potential miRNA identification. Using known miRNA data, our support vector machine (SVM) model predicted miRNAs with an average Matthews correlation coefficient (MCC) of 0.939 over 32 human cell datasets and outperformed miRDeep2 and miRAnalyzer regarding phylogenetic conservation. The A-to-I editing detection strongly correlated with a reference dataset with adjusted R2 = 0.96. miRge 2.0 is the most up-to-date aligner with custom libraries to both miRBase v22 and MirGeneDB v2.0 for 6 species: human, mouse, rat, fruit fly, nematode and zebrafish; and has a tool to create custom libraries. For user-friendliness, miRge 2.0 is incorporated into bcbio-nextgen and implementable through Bioconda.

CONCLUSIONS: miRge 2.0 is a redesigned, leading miRNA RNA-seq aligner with several improvements and novel utilities. miRge 2.0 is freely available at: https://github.com/mhalushka/miRge .}, } @article {pmid30153798, year = {2018}, author = {Ferreira Vicente, A and Girault, G and Corde, Y and Souza Ribeiro Mioni, M and Borges Keid, L and Jay, M and Megid, J and Mick, V}, title = {New insights into phylogeography of worldwide Brucella canis isolates by comparative genomics-based approaches: focus on Brazil.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {636}, pmid = {30153798}, issn = {1471-2164}, support = {2014/00889-0//FAPESP/ ; 88887.117958/2016-00//CAPES/ ; 291815-FP7/ERANET/ ANIHWA//Bru-EPIDIA/ ; }, mesh = {Brazil ; Brucella canis/*classification/*genetics ; *Genomics ; *Phylogeography ; }, abstract = {BACKGROUND: Canine brucellosis, due to Brucella canis, is a worldwide zoonosis that remains endemic in South America, including Brazil. Implementation of powerful whole-genome sequencing approaches allowed exploring the Brucella genus considered as monomorphic, with, to date, more than 500 genomes available in public databases. Nevertheless, with under-representation of B. canis genomes -only twenty complete or draft genomes-, lack of knowledge about this species is still considerable. This report describes a comparative genomics-based phylogeographic investigation of 53 B. canis strains, including 28 isolates paired-end sequenced in this work.

RESULTS: Obtained results allow identifying a SNP panel species-specific to B. canis of 1086 nucleotides. In addition, high-resolution analyses assess the epidemiological relationship between worldwide isolates. Our findings show worldwide strains are distributed among 2 distinct lineages. One of them seems to be specific to South American strains, including Brazil. B. canis South American strains may be identified by a SNP panel of 15 nucleotides, whereas a 22 SNP panel is sufficient to define contamination origin from Brazil. These results lead to the proposal of a possible spread route for dog brucellosis through South America. Additionally, whole-genome analyses highlight the remarkable genomic stability of B. canis strains over time and the sustainability of the infection in São Paulo over 12 year-period.

CONCLUSIONS: Significant increase of B. canis genomes available in public databases provides new insights into B. canis infection in South America, including Brazil, as well as in the world, and also offers new perspectives for the Brucella genus largo sensu.}, } @article {pmid30153793, year = {2018}, author = {He, Z and Fischer, A and Song, Y and Steele, M and Guan, LL}, title = {Genome wide transcriptome analysis provides bases on colonic mucosal immune system development affected by colostrum feeding strategies in neonatal calves.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {635}, pmid = {30153793}, issn = {1471-2164}, support = {2015B013//Alberta Livestock and Meat Agency Ltd/ ; }, mesh = {Animals ; Animals, Newborn ; Cattle ; Colon/*immunology/*metabolism ; Colostrum/*metabolism ; Dairying ; *Gene Expression Profiling ; *Genomics ; Intestinal Mucosa/*immunology/*metabolism ; Male ; Time Factors ; }, abstract = {BACKGROUND: Delivery of colostrum within the first several hours after birth is vital for establishing successful passive immunity in neonatal dairy calves. However, it is unclear whether a difference in colostrum feeding strategy can affect the development of the calf gastrointestinal tract. The aim of this study was to evaluate the effect of colostrum feeding time within the first 12 h after birth on the colonic mucosal immune system in neonatal calves using a genome wide transcriptome analysis.

RESULTS: RNA sequencing-based transcriptome analysis of colon tissues collected from 27 male Holstein calves which were randomly assigned to one of three colostrum feeding strategies - (immediately after birth (TRT0); 6 h after birth (TRT6); 12 h after birth (TRT12)) - and euthanized at 51 h of age detected 15,935 ± 210, 15,332 ± 415, and 15,539 ± 440 expressed genes in the colon under three treatments, respectively. The core transcriptome of the colon included 12,678 genes, with enriched "cellular process" and "metabolic process" as the top two biological functions with 802 of them being immune function related genes. Principal component analysis of the colon transcriptomes did not display a clear separation by colostrum feeding strategy and differential abundance analyses showed no significant difference in the expression of immune related genes among the treatments. Additionally, a weighted gene co-expression network analysis identified 4 significant (|correlation| > 0.50 and p ≤ 0.05) gene modules consisting of 122 immune related genes, which were positively or negatively correlated with the abundance of Lactobacillus and Faecalibacterium prausnitzii in the colon.

CONCLUSION: Transcriptome analysis indicates that the development of the colonic mucosal immune system in neonatal calves may be independent of the timing of initial colostrum meal within 12 h after birth. Our results also provide a molecular understanding of colonic biological function in neonatal calves and extends knowledge on how host gene expression profiles are associated with the abundance of specific bacterial groups in the colon.}, } @article {pmid30153743, year = {2018}, author = {Lu, HJ and Chang, L}, title = {Reciprocity Among Preschoolers in Relation to Resource Allocation Toward Siblings, Friends, and Strangers.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918797031}, doi = {10.1177/1474704918797031}, pmid = {30153743}, issn = {1474-7049}, mesh = {*Altruism ; Child ; Child, Preschool ; Female ; Friends ; Humans ; *Interpersonal Relations ; Male ; *Resource Allocation ; Siblings ; Social Behavior ; }, abstract = {Children at age 6 years differentially treat kin, friends, and strangers in resource allocation games by being more altruistic toward kin. However, it is unknown how previous allocation experience as a recipient influences the potential kinship effect in subsequent resource allocations. The present study investigated how 4- to 6-year-old children allocated resources between themselves and a sibling, a friend, or a stranger in three allocation tasks after the recipient had previously shared or nonshared with the participant. Results showed that, when a share would induce cost on the self, 6-year-old children were likely to share with a sibling whether the sibling had previously shared or not, but they would share only with friends or strangers who had previously shared. When a share would induce no cost, participants across ages were likely to share with a recipient who had previously shared. When the decision option was between sharing equally and sharing altruistically, participants would allow the recipient to have more only when the recipient was a sibling or friend who had previously allocated altruistically. These findings suggest that kin altruism in resource allocation emerges at around 6 years of age and that reciprocity partly overrides and partly reinforces kin altruism.}, } @article {pmid30153503, year = {2018}, author = {Ran, JH and Shen, TT and Wu, H and Gong, X and Wang, XQ}, title = {Phylogeny and evolutionary history of Pinaceae updated by transcriptomic analysis.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {106-116}, doi = {10.1016/j.ympev.2018.08.011}, pmid = {30153503}, issn = {1095-9513}, abstract = {Pinaceae comprises 11 genera, and represents the largest family of conifers with an extensive wild distribution in the Northern Hemisphere. Intergeneric relationships of Pinaceae have been investigated using many morphological characters and molecular markers, but phylogenetic positions of four genera, including Cathaya, Cedrus, Nothotsuga and Pseudolarix, remain controversial or have not been completely resolved. To completely resolve the intergeneric relationships of Pinaceae, we conducted a comparative transcriptomic study of 14 species representing all Pinaceae genera. Multiple data sets, containing up to 6,369,681 sites across 4676 loci, were analyzed using concatenation and coalescent methods. Our study generated a robust topology, which divides Pinaceae into two clades, one (pinoid) including Cathaya, Larix, Picea, Pinus, and Pseudotsuga, and the other (abietoid) including Abies, Cedrus, Keteleeria, Nothotsuga, Pseudolarix, and Tsuga. Cathaya and Pinus form a clade sister to Picea; Cedrus is sister to the remaining abietoid genera, and the two genera Nothotsuga and Tsuga form a clade sister to Pseudolarix. The discordant positions of Cathaya, Cedrus and Pseudolarix in different gene trees could be explained by ancient radiation and/or molecular homoplastic evolution. The hybrid origin hypothesis of Nothotsuga is not supported. Based on molecular dating, extant Pinaceae genera diverged since about 206 Mya, earlier than the break-up of Pangea, and the divergence among the pinoid genera occurred earlier than the split among the abietoid genera. Moreover, our study indicates that two radiation events occurred in the evolution of Pinaceae genera, and some important morphological characters evolved multiple times based on ancestral state reconstruction.}, } @article {pmid30153502, year = {2018}, author = {Samanta, B and Ehrman, JM and Kaczmarska, I}, title = {A consensus secondary structure of ITS2 for the diatom Order Cymatosirales (Mediophyceae, Bacillariophyta) and reappraisal of the order based on DNA, morphology, and reproduction.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {117-129}, doi = {10.1016/j.ympev.2018.08.014}, pmid = {30153502}, issn = {1095-9513}, abstract = {In 1983, Hasle and colleagues removed cymatosiroid diatoms from the pennates, and erected a new centric diatom family, the Cymatosiraceae, mainly to accommodate for their newly discovered mode of sexual reproduction. The new family consisted of two subfamilies differing in frustule structure. The family was later elevated to the rank of Order Cymatosirales Round and Crawford. We revisited intra-ordinal relationships within Cymatosirales using combined genetic (DNA sequences), morphological (valve and frustule structure), and reproductive (auxospore type) characters. In total, 36 cymatosiroid strains from 19 species representing 13 genera (80% of the total number of extant genera; nine of them represented by their generitypes) were used in this study. Instead of only the commonly used loci (18S rRNA and plastidal genes) to infer diatom phylogeny, we developed a consensus secondary structure model of the Internal Transcribed Spacer 2 (ITS2) for this order and applied it to aid in sequence alignments for ITS2. This improved the alignment and thus the robustness of the phylogenetic framework. The compensatory base changes (CBCs) found in ITS2 secondary structures were mapped onto the multi-gene (18S rRNA + ITS2 + rbcL) phylogenetic tree topology. In all these trees, all species grouped into two morphologically and genetically distinct clades. Each clade was supported by multiple CBCs, as did all the clades representing genera. However, these clades did not correspond to the previously established subfamilies. Consequently, we amend the Order Cymatosirales and family Cymatosiraceae, and propose a new family, the Leyanellaceae. The structure of the auxospore was an additional synapomorphic character for Cymatosirales. Overall, we demonstrate a novel approach to study diatom phylogeny across a broader taxonomic range using ITS2 secondary structural information. Our results suggest that this approach might be useful in establishing higher taxonomic relationships in other groups of diatoms.}, } @article {pmid30153501, year = {2018}, author = {Volis, S and Fogel, K and Tu, T and Sun, H and Zaretsky, M}, title = {Evolutionary history and biogeography of Mandragora L. (Solanaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {85-95}, doi = {10.1016/j.ympev.2018.08.015}, pmid = {30153501}, issn = {1095-9513}, abstract = {Mandragora L. (Solanaceae) is the only genus of the tribe Mandragoreae, one of the two tribes of the cosmopolitan nightshade family, which occur exclusively in Eurasia and northern Africa. The genus occurs discontinuously in the Mediterranean region, Turanian region, and on the Tibetan Plateau, representing a classical disjunction pattern in the biogeography of the Old World flora. In this study, we reconstructed the genus phylogeny using AFLP, eight plastid DNA regions and one nuclear (ITS) gene, and evaluated the taxonomic value of quantitative traits time to flowering, fruit and seed size. We also analyzed the evolutionary history of the genus based on a phylogenetic framework and dating inferred from a combined data set of seven plastid regions with one fossil calibration point. Our data suggest that Mandragora originated in the Eocene, apparently along the Tethyan coast in broadleaf deciduous mesophytic forests that covered most of the Mediterranean region at that time. The Mediterranean-Turanian clade diverged from the Tibetan Plateau clade about 20.5 million years ago (Ma) as a result of the plateau uplift which probably was enhanced by aridification in the interior of Eurasia. A second split within the genus occurred about 11.1 Ma and resulted in Western Mediterranean and Near East-Turanian clades. Mandragora turcomanica was found to have very closely related evolutionary history with plants from the Near East indicating a possible ancient human assisted migration from Israel to Persia in historic times. In the Tibetan Plateau area, the morphologically distinctive M. chinghaiensis is nested within the M. caulescens clade indicating a very recent diversification within this lineage.}, } @article {pmid30153500, year = {2018}, author = {Anoop, VK and Dahanukar, N and Philip, S and Thomas, L and Raghavan, R}, title = {Phylogeny of the hillstream loach genus Mesonoemacheilus reveals widespread diversification through ancient drainage connections in the Western Ghats Biodiversity Hotspot.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {77-84}, doi = {10.1016/j.ympev.2018.08.013}, pmid = {30153500}, issn = {1095-9513}, abstract = {Rivers draining the Western Ghats (WG) mountain ranges in peninsular India harbor an exceptionally diverse, unique and evolutionarily distinct assemblage of lower vertebrates with high levels of endemism, attributed to their evolution and potentially long history of isolation during the Late Cretaceous or Early Tertiary. A molecular phylogeny of hillstream loaches of the genus Mesonoemacheilus endemic to the WG revealed the presence of four clades which we designate as 'species groups'. A consensus of various species delimitation methods indicates the likelihood of 'at least' seven more undescribed species within Mesonoemacheilus. Molecular clock analysis dates the basal clade around 38 mya in the Paleogene, and subsequent diversification in the Neogene and Quaternary periods resulting in the current genetic diversity. Biogeographic analysis suggests that vicariance events which separated the rivers on either side of the two geological barriers/gaps, the Palghat and Shencottah, in the Neogene, as well as range contractions and cladogenetic events contributed to the current patterns of diversity and distribution of this genus. Our results also provide preliminary indications on the interconnections and faunal exchange between historical river drainages in the WG region.}, } @article {pmid30153454, year = {2018}, author = {Ustiyan, V and Bolte, C and Zhang, Y and Han, L and Xu, Y and Yutzey, KE and Zorn, AM and Kalin, TV and Shannon, JM and Kalinichenko, VV}, title = {FOXF1 transcription factor promotes lung morphogenesis by inducing cellular proliferation in fetal lung mesenchyme.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {50-63}, pmid = {30153454}, issn = {1095-564X}, support = {R01 HL084151/HL/NHLBI NIH HHS/United States ; R01 HL123490/HL/NHLBI NIH HHS/United States ; R01 HL132849/HL/NHLBI NIH HHS/United States ; R01 HL141174/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell Proliferation ; Forkhead Transcription Factors/*genetics/*metabolism/physiology ; Gene Expression Regulation, Developmental/genetics ; Lung/cytology/*embryology/metabolism ; Mesoderm/metabolism ; Mice/embryology ; Mice, Inbred C57BL ; Mice, Knockout ; Organogenesis/physiology ; Transcription Factors/metabolism ; Transcriptome/genetics ; }, abstract = {Organogenesis is regulated by mesenchymal-epithelial signaling events that induce expression of cell-type specific transcription factors critical for cellular proliferation, differentiation and appropriate tissue patterning. While mesenchymal transcription factors play a key role in mesenchymal-epithelial interactions, transcriptional networks in septum transversum and splanchnic mesenchyme remain poorly characterized. Forkhead Box F1 (FOXF1) transcription factor is expressed in mesenchymal cell lineages; however, its role in organogenesis remains uncharacterized due to early embryonic lethality of Foxf1-/- mice. In the present study, we generated mesenchyme-specific Foxf1 knockout mice (Dermo1-Cre Foxf1-/-) and demonstrated that FOXF1 is required for development of respiratory, cardiovascular and gastrointestinal organ systems. Deletion of Foxf1 from mesenchyme caused embryonic lethality in the middle of gestation due to multiple developmental defects in the heart, lung, liver and esophagus. Deletion of Foxf1 inhibited mesenchyme proliferation and delayed branching lung morphogenesis. Gene expression profiling of micro-dissected distal lung mesenchyme and ChIP sequencing of fetal lung tissue identified multiple target genes activated by FOXF1, including Wnt2, Wnt11, Wnt5A and Hoxb7. FOXF1 decreased expression of the Wnt inhibitor Wif1 through direct transcriptional repression. Furthermore, using a global Foxf1 knockout mouse line (Foxf1-/-) we demonstrated that FOXF1-deficiency disrupts the formation of the lung bud in foregut tissue explants. Finally, deletion of Foxf1 from smooth muscle cell lineage (smMHC-Cre Foxf1-/-) caused hyper-extension of esophagus and trachea, loss of tracheal and esophageal muscle, mispatterning of esophageal epithelium and decreased proliferation of smooth muscle cells. Altogether, FOXF1 promotes lung morphogenesis by regulating mesenchymal-epithelial signaling and stimulating cellular proliferation in fetal lung mesenchyme.}, } @article {pmid30152871, year = {2018}, author = {Maddamsetti, R and Johnson, DT and Spielman, SJ and Petrie, KL and Marks, DS and Meyer, JR}, title = {Gain-of-function experiments with bacteriophage lambda uncover residues under diversifying selection in nature.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2234-2243}, doi = {10.1111/evo.13586}, pmid = {30152871}, issn = {1558-5646}, support = {ELSI Origins Network//John Templeton Foundation/ ; }, abstract = {Viral gain-of-function mutations frequently evolve during laboratory experiments. Whether the specific mutations that evolve in the lab also evolve in nature and whether they have the same impact on evolution in the real world is unknown. We studied a model virus, bacteriophage λ, that repeatedly evolves to exploit a new host receptor under typical laboratory conditions. Here, we demonstrate that two residues of λ's J protein are required for the new function. In natural λ variants, these amino acid sites are highly diverse and evolve at high rates. Insertions and deletions at these locations are associated with phylogenetic patterns indicative of ecological diversification. Our results show that viral evolution in the laboratory mirrors that in nature and that laboratory experiments can be coupled with protein sequence analyses to identify the causes of viral evolution in the real world. Furthermore, our results provide evidence for widespread host-shift evolution in lambdoid viruses.}, } @article {pmid30152817, year = {2018}, author = {Wells, JCK}, title = {Life history trade-offs and the partitioning of maternal investment: Implications for health of mothers and offspring.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {153-166}, pmid = {30152817}, issn = {2050-6201}, abstract = {Lay Summary: This review sets out the hypothesis that life history trade-offs in the maternal generation favour the emergence of similar trade-offs in the offspring generation, mediated by the partitioning of maternal investment between pregnancy and lactation, and that these trade-offs help explain widely reported associations between growth trajectories and NCD risk. Growth patterns in early life predict the risk of non-communicable diseases (NCDs), but adaptive explanations remain controversial. It is widely assumed that NCDs occur either because of physiological adjustments to early constraints, or because early ecological cues fail to predict adult environmental conditions (mismatch). I present an inter-generational perspective on developmental plasticity, based on the over-arching hypothesis that a key axis of variability in maternal metabolism derives from life history trade-offs, which influence how individual mothers partition nutritional investment in their offspring between pregnancy and lactation. I review evidence for three resulting predictions: (i) Allocating relatively more energy to growth during development promotes the capacity to invest in offspring during pregnancy. Relevant mechanisms include greater fat-free mass and metabolic turnover, and a larger physical space for fetal growth. (ii) Allocating less energy to growth during development constrains fetal growth of the offspring, but mothers may compensate by a tendency to attain higher adiposity around puberty, ecological conditions permitting, which promotes nutritional investment during lactation. (iii) Since the partitioning of maternal investment between pregnancy and lactation impacts the allocation of energy to 'maintenance' as well as growth, it is expected to shape offspring NCD risk as well as adult size and body composition. Overall, this framework predicts that life history trade-offs in the maternal generation favour the emergence of similar trade-offs in the offspring generation, mediated by the partitioning of maternal investment between pregnancy and lactation, and that these trade-offs help explain widely reported associations between growth trajectories and NCD risk.}, } @article {pmid30152815, year = {2018}, author = {Macintosh, AA and Wells, JCK and Stock, JT}, title = {Maternal investment, maturational rate of the offspring and mechanical competence of the adult female skeleton.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {167-179}, pmid = {30152815}, issn = {2050-6201}, abstract = {Lay summary: Girls with a slower life history trajectory build a larger body with larger and mechanically stronger bones. Thus, variation in the emergence of slower versus faster life history trajectories during development can have consequences for bone mechanical competence, and hence fracture risk in adulthood.

Background and objectives: Variation in life history trajectory, specifically relative investment in growth versus reproduction, has been associated with chronic disease risk among women, but whether this scenario extends to skeletal health and fracture risk is unknown. This study investigates the association of life history traits (proxies for maternal investment and maturational rate) with female bone outcomes in adulthood.

Methodology: Body size variables, regional muscle and fat areas, and cross-sectional bone size and strength outcomes were obtained from 107 pre-menopausal women encompassing a wide range of physical activity levels. Developmental parameters (birth weight, age at menarche) were obtained from questionnaires.

Results: High birth weight was significantly associated with a proportionately larger body and larger, mechanically stronger bones, independently of physical activity level. It was also positively but non-significantly associated with age at menarche. Later menarche was significantly associated with larger and mechanically stronger bones and substantially less absolute and relative regional subcutaneous fat. Age at menarche exhibited stronger relationships with adult adiposity than did physical activity.

Conclusions and implications: Both larger birth weight and later menarche contribute to a slower life history trajectory, which is associated with greater body size, leanness and bone mechanical competence in early adulthood. In contrast, earlier sexual maturity prioritized energy allocation in adiposity over body size and skeletal strength. Thus, the level of maternal investment and the woman's own life history trajectory shape investment in skeletal properties, with implications for fracture risk later in life.}, } @article {pmid30152751, year = {2018}, author = {Fang, XM and Bai, JL and Zhang, DW and Su, J and Zhao, LL and Liu, HY and Zhang, YQ and Yu, LY}, title = {Roseomonas globiformis sp. nov., an airborne bacteria isolated from an urban area of Beijing.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3301-3306}, doi = {10.1099/ijsem.0.002985}, pmid = {30152751}, issn = {1466-5034}, mesh = {*Air Microbiology ; Bacterial Typing Techniques ; Base Composition ; Beijing ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Methylobacteriaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A novel dark pink pigmented bacterium, designated strain CPCC 100847T (deposited with strain code 0113-15), was isolated from the urban air of Beijing, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CPCC 100847T was related to members of the genus Roseomonas and had the highest 16S rRNA gene sequence similarity to Roseomonas aestuarii JC17T (97.5 %). A low level of DNA-DNA relatedness (18.7 %) with its closest type strain R. aestuarii JC17T (KCTC 22692T) proved that strain CPCC 100847T belonged to a unique genomic species. CPCC 100847T had many common characteristics of the genus Roseomonas, but also had a range of cultural, physiological and biochemical characteristics that separated it from related Roseomonas species. Cells were Gram-negative, cocci- to oval-shaped, non-motile, non-endospore-forming and strictly aerobic. The respiratory ubiquinone was Q-10. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, an unidentified aminolipid and an unidentified phospholipid. The major fatty acids (>5 %) were C18 : 1ω7c, anteiso-C15 : 0, C16 : 0, iso-C15 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The combined genotypic and phenotypic data indicated that the isolate represents a novel species of the genus Roseomonas. The name proposed for this species is Roseomonasglobiformis sp. nov., with CPCC 100847T (=KCTC 52094T) as the type strain. The DNA G+C composition is 65.2 mol%.}, } @article {pmid30152750, year = {2018}, author = {Huang, H and Liu, M and Zhong, W and Mo, K and Zhu, J and Zou, X and Hu, Y and Bao, S}, title = {Streptomyces caeni sp. nov., isolated from mangrove mud.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3080-3083}, doi = {10.1099/ijsem.0.002916}, pmid = {30152750}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhizophoraceae/*microbiology ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; }, abstract = {A novel aerobic actinomycete, designated as HA15955T, was isolated from a mangrove mud sample collected in Sanya, China. Scanning electron microscopy revealed that HA15955T produced straight to spiral spore chains with smooth cylindrical spores. 16S rRNA gene sequence similarity showed that strain HA15955T belonged to the genus Streptomyces, was most closely related to Streptomyces speibonae NRRL B-24240T (98.7 % similarity) and formed a distinct subclade. The low relatedness value of DNA-DNA hybridization showed that it formed a distinct genomic species. Based on phenotypic, genotypic and phylogenetic data, strain HA15955T should be classified as a novel species of the genus Streptomyces, for which the name Streptomycescaeni sp. nov. is proposed. The type strain is HA15955T (=CGMCC 4.7426T=DSM 105693T).}, } @article {pmid30152749, year = {2018}, author = {Gao, WL and Liu, KF and Yao, LG and Hui, FL}, title = {Pichia nanzhaoensis sp. nov. and Pichia paraexigua f.a., sp. nov., two yeast species isolated from rotting wood.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3311-3315}, doi = {10.1099/ijsem.0.002989}, pmid = {30152749}, issn = {1466-5034}, mesh = {China ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Mycological Typing Techniques ; *Phylogeny ; Pichia/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Spores, Fungal ; Wood/*microbiology ; }, abstract = {Four yeast strains were isolated from rotting wood samples collected in the Baotianman Nature Reserve in Henan Province, Central China. On the basis of sequence analysis of the D1/D2 domains of the large subunit rRNA gene and the internal transcribed spacer regions, they were suggested to be two novel species of the genus Pichia. Pichia nanzhaoensis sp. nov. produces one to four spherical ascospores per ascus, and is most closely related to Candida pseudolambica. Pichia paraexigua f.a., sp. nov. is a sister taxa to Pichia exigua, but the formation of ascospores was not observed on various sporulation media. P. nanzhaoensis sp. nov. can weakly assimilate inulin, whereas P. paraexigua sp. nov. can weakly assimilate d-glucosamine. The type strain of Pichia nanzhaoensis is NYNU 178136T (=CICC 33279T=CBS 15346T) and the type strain of Pichia paraexigua is NYNU 178135T (=CICC 33278T=CBS 15237T).}, } @article {pmid30152037, year = {2018}, author = {Briolat, ES and Burdfield-Steel, ER and Paul, SC and Rönkä, KH and Seymoure, BM and Stankowich, T and Stuckert, AMM}, title = {Diversity in warning coloration: selective paradox or the norm?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12460}, pmid = {30152037}, issn = {1469-185X}, abstract = {Aposematic theory has historically predicted that predators should select for warning signals to converge on a single form, as a result of frequency-dependent learning. However, widespread variation in warning signals is observed across closely related species, populations and, most problematically for evolutionary biologists, among individuals in the same population. Recent research has yielded an increased awareness of this diversity, challenging the paradigm of signal monomorphy in aposematic animals. Here we provide a comprehensive synthesis of these disparate lines of investigation, identifying within them three broad classes of explanation for variation in aposematic warning signals: genetic mechanisms, differences among predators and predator behaviour, and alternative selection pressures upon the signal. The mechanisms producing warning coloration are also important. Detailed studies of the genetic basis of warning signals in some species, most notably Heliconius butterflies, are beginning to shed light on the genetic architecture facilitating or limiting key processes such as the evolution and maintenance of polymorphisms, hybridisation, and speciation. Work on predator behaviour is changing our perception of the predator community as a single homogenous selective agent, emphasising the dynamic nature of predator-prey interactions. Predator variability in a range of factors (e.g. perceptual abilities, tolerance to chemical defences, and individual motivation), suggests that the role of predators is more complicated than previously appreciated. With complex selection regimes at work, polytypisms and polymorphisms may even occur in Müllerian mimicry systems. Meanwhile, phenotypes are often multifunctional, and thus subject to additional biotic and abiotic selection pressures. Some of these selective pressures, primarily sexual selection and thermoregulation, have received considerable attention, while others, such as disease risk and parental effects, offer promising avenues to explore. As well as reviewing the existing evidence from both empirical studies and theoretical modelling, we highlight hypotheses that could benefit from further investigation in aposematic species. Finally by collating known instances of variation in warning signals, we provide a valuable resource for understanding the taxonomic spread of diversity in aposematic signalling and with which to direct future research. A greater appreciation of the extent of variation in aposematic species, and of the selective pressures and constraints which contribute to this once-paradoxical phenomenon, yields a new perspective for the field of aposematic signalling.}, } @article {pmid30151880, year = {2018}, author = {Reza, AMMT and Choi, YJ and Han, SG and Song, H and Park, C and Hong, K and Kim, JH}, title = {Roles of microRNAs in mammalian reproduction: from the commitment of germ cells to peri-implantation embryos.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12459}, pmid = {30151880}, issn = {1469-185X}, abstract = {MicroRNAs (miRNAs) are active regulators of numerous biological and physiological processes including most of the events of mammalian reproduction. Understanding the biological functions of miRNAs in the context of mammalian reproduction will allow a better and comparative understanding of fertility and sterility in male and female mammals. Herein, we summarize recent progress in miRNA-mediated regulation of mammalian reproduction and highlight the significance of miRNAs in different aspects of mammalian reproduction including the biogenesis of germ cells, the functionality of reproductive organs, and the development of early embryos. Furthermore, we focus on the gene expression regulatory feedback loops involving hormones and miRNA expression to increase our understanding of germ cell commitment and the functioning of reproductive organs. Finally, we discuss the influence of miRNAs on male and female reproductive failure, and provide perspectives for future studies on this topic.}, } @article {pmid30151822, year = {2018}, author = {Warren, BH and Hagen, O and Gerber, F and Thébaud, C and Paradis, E and Conti, E}, title = {Evaluating alternative explanations for an association of extinction risk and evolutionary uniqueness in multiple insular lineages.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2005-2024}, doi = {10.1111/evo.13582}, pmid = {30151822}, issn = {1558-5646}, support = {267243//Plant Fellows International Postdoc Fellowship Programme/ ; EU Seventh Framework Programme//Plant Fellows International Postdoc Fellowship Programme/ ; 2006-BDIV002//ANR Biotas/ ; //Claraz Schenkung/ ; }, abstract = {Studies in insular environments have often documented a positive association of extinction risk and evolutionary uniqueness (i.e., how distant a species is from its closest living relative). However, the cause of this association is unclear. One explanation is that species threatened with extinction are evolutionarily unique because they are old, implying that extinction risk increases with time since speciation (age-dependent extinction). An alternative explanation is that such threatened species are last survivors of clades that have undergone an elevated extinction rate, and that their uniqueness results from the extinction of their close relatives. Distinguishing between these explanations is difficult but important, since they imply different biological processes determining extinction patterns. Here, we designed a simulation approach to distinguish between these alternatives using living species, and applied it to 12 insular radiations that show a positive association between extinction risk and evolutionary uniqueness. We also tested the sensitivity of results to underlying assumptions and variable extinction rates. Despite differences among the radiations considered, age-dependent extinction was supported as best explaining the majority of the empirical cases. Biological processes driving characteristic changes in abundance with species duration (age-dependency) may merit further investigation.}, } @article {pmid30151557, year = {2018}, author = {Shahpiri, A and Mohammadzadeh, A}, title = {Bioaccumulation of Arsenic by Engineered Escherichia coli Cells Expressing Rice Metallothionein Isoforms.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1537-1542}, pmid = {30151557}, issn = {1432-0991}, support = {97000792//Iran National Science Foundation/ ; }, mesh = {Arsenic/*metabolism ; Escherichia coli/*genetics/*metabolism ; Genetic Engineering ; Metallothionein/*genetics/metabolism ; Oryza/*genetics ; Plant Proteins/*genetics/metabolism ; Protein Isoforms/genetics/metabolism ; Recombinant Proteins/genetics/metabolism ; }, abstract = {Metallothioneins (MTs) are low-molecular weight cysteine (Cys)-rich proteins with high metal-binding capacity. Based on the Cys arrangement in their amino acid sequences, plant MTs are categorized into four classes. This study evaluated the ability of genetically engineered Escherichia coli cells, which express four rice MT isoforms as fusion proteins with glutathione-S-transferase (GST), to remove arsenic. As compared with control strain, the expression of GST-OsMT1, GST-OsMT2, GST-OsMT3, and GST-OsMT4 resulted in 8-, 5.6-, 3-, and 1.1-fold-higher As3+ accumulation. The recombinant GST-OsMT isoforms were purified using affinity chromatography and their apo-forms were prepared. The ability of the GST-OsMT2 isoform to bind with As3+ in vitro was also confirmed by ultraviolet (UV) absorption spectra recorded after the reconstitution of apo-proteins with As3+. However, the formation of complexes of other MT isoforms with arsenic was not observed.}, } @article {pmid30151556, year = {2018}, author = {Shen, J and Yu, Z and Zhu, W}, title = {Insights into the Populations of Proteolytic and Amino Acid-Fermenting Bacteria from Microbiota Analysis Using In Vitro Enrichment Cultures.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1543-1550}, pmid = {30151556}, issn = {1432-0991}, support = {31402101//National Natural Science Foundation of China/ ; BK20140696//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {Amino Acids/*metabolism ; Ammonia/metabolism ; Animals ; Antifungal Agents/pharmacology ; Bacteria/classification/drug effects/isolation & purification/*metabolism ; Cattle ; Cell Culture Techniques ; DNA, Bacterial/genetics ; Fermentation ; *Microbiota/drug effects ; Monensin/pharmacology ; Phylogeny ; Proteolysis ; RNA, Ribosomal, 16S/genetics ; Rumen/*microbiology ; }, abstract = {This study evaluated the effects of nitrogen source composition and monensin on the populations of proteolytic and amino acid-fermenting bacteria using in vitro enrichment culture. The experiment was designed with a 2 × 2 factorial arrangement: two nitrogen sources, casein (Cas) and tryptone (Try), and two levels of monensin, 0 (C) and 5 µmol/L (M), resulting in four treatments: Cas-C, Cas-M, Try-C, and Try-M. Ruminal fluid collected from three cannulated Holstein dairy cows was used as the inoculum. Each treatment culture was consecutively transferred six times after 24 h of incubation. The results showed that ammonia concentration was lower in Cas than in Try, and it was reduced by monensin addition. In the 6th transfer enrichment cultures, the 16S rRNA gene copy numbers of total bacteria were reduced by monensin but was unaffected by nitrogen sources. Principal component analysis showed that the bacterial communities differed among the treatments. At the genus level, Peptostreptococcus accounted for as much as 41% of the total bacteria in Try-C, but it made up less than 0.02% in the other three treatments. A Pearson correlation analysis showed that the relative abundance of Peptostreptococcus was positively correlated with ammonia concentration. Overall, the results suggest that nitrogen source composition and monensin can affect ruminal ammonia production by modulating the ruminal proteolytic bacterial communities, and some hyper-ammonia-producing bacteria of the genus Peptostreptococcus may be among the main culprits contributing to the high ammonia concentration in the rumen.}, } @article {pmid30151194, year = {2018}, author = {Ojha, A and Watve, M}, title = {Blind fish: An eye opener.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {186-189}, pmid = {30151194}, issn = {2050-6201}, abstract = {Lay Summary: Different species of vertebrates have conditions similar to human obesity, insulin resistance and type 2 diabetes. Increasing number of studies are now revealing that the causes and interrelationships between these states are substantially different in different species. Comparative physiology may turn out to be an eye opener for evolutionary theories of diabetes. Obesity induced insulin resistance is believed to be central to type 2 diabetes. Recent work on Mexican cavefish, Astyanax mexicanus, has revealed a hyperglycemic phenotype similar to human type 2 diabetes but here insulin resistance is the cause of obesity rather than an effect. Instead of developing diabetic complications, the hyperglycemic fish lead a healthy and long life. In addition to fish, insulin resistance in hibernating bears, dolphins, horses, bonnet macaques and chimpanzees demonstrate that the relationship between diet, obesity, insulin sensitivity and diabetes is widely different in different species. Evolutionary hypotheses about type 2 diabetes should explain these differences.}, } @article {pmid30151193, year = {2018}, author = {Renz-Polster, H and De Bock, F}, title = {Deformational plagiocephaly: The case for an evolutionary mismatch.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {180-185}, pmid = {30151193}, issn = {2050-6201}, abstract = {Lay Summary: In industrialized societies some babies develop flattening of the back part of their head. It is thought that this comes from sleeping supine, which has been shown to be the safest option for babies. However, this explanation cannot be correct from an evolutionary standpoint: why should safe sleep come at the cost of a misshaped head? Babies in industrialized societies are generally healthy. The medical problems they may be afflicted with are usually well understood. Deformational plagiocephaly presents a notable exception. In many industrialized countries, one in six babies shows posterior flattening of the skull-a feature noteworthy from an evolutionary perspective as the well rounded cranium is part of the 'Kindchenschema' evolved to secure care for the infant. It is commonly held that the deformation of the posterior cranium occurs as a consequence of the supine sleep position, now advocated as the safest sleep position for babies by medical experts. This explanation, however, does not fare well in the light of evolutionary theory: why should safe sleep come at the cost of a social handicap? Here, we present an alternative hypothesis that is grounded on evolutionary mismatch theory and exemplifies how evolutionary reasoning can help clarify medical conditions relevant to today's public health.}, } @article {pmid30151185, year = {2018}, author = {Pacyna, AD and Ruman, M and Mazerski, J and Polkowska, Ż}, title = {Biological responses to environmental contamination. How can metal pollution impact signal honesty in avian species?.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7733-7739}, pmid = {30151185}, issn = {2045-7758}, abstract = {Environmental pollution, for example with metals, can significantly affect the ecosystem balance leading to severe changes. Biologically active pigments are relevant for the appearance and condition of birds. Melanin and carotenoid particles are the most frequently deposited pigments in avian integument. They are responsible for the majority of colors of bird plumage. The phenotypic expression can be affected by metal contamination. It can be manifested as color bleaching or differences in the size of plumage badges. In this study, we performed a comprehensive review of related studies in order to estimate the underlying population effect of this potential dependency. The study is based on the review of the literature regarding several avian species. It was designed to identify an area where the effect of the exposure is still poorly known. The analysis was specifically conducted to investigate the correlation between trace element concentration and eumelanin deposition. Moreover, we searched for factors that could affect spectral properties of feathers with carotenoid-based pigmentation. As a result, we found carotenoid-based pigmentation to be of a good use in terms of visual condition assessment. Changes in melanin-based pattern should be analyzed separately for eu- and pheomelanin as well as for a range of essential and toxic elements. Comprehensive studies on the subject are still scarce. Therefore, the issue requires further investigation.}, } @article {pmid30151184, year = {2018}, author = {Gutiérrez, Y and Ott, D and Töpperwien, M and Salditt, T and Scherber, C}, title = {X-ray computed tomography and its potential in ecological research: A review of studies and optimization of specimen preparation.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7717-7732}, pmid = {30151184}, issn = {2045-7758}, abstract = {Imaging techniques are a cornerstone of contemporary biology. Over the last decades, advances in microscale imaging techniques have allowed fascinating new insights into cell and tissue morphology and internal anatomy of organisms across kingdoms. However, most studies so far provided snapshots of given reference taxa, describing organs and tissues under "idealized" conditions. Surprisingly, there is an almost complete lack of studies investigating how an organism's internal morphology changes in response to environmental drivers. Consequently, ecology as a scientific discipline has so far almost neglected the possibilities arising from modern microscale imaging techniques. Here, we provide an overview of recent developments of X-ray computed tomography as an affordable, simple method of high spatial resolution, allowing insights into three-dimensional anatomy both in vivo and ex vivo. We review ecological studies using this technique to investigate the three-dimensional internal structure of organisms. In addition, we provide practical comparisons between different preparation techniques for maximum contrast and tissue differentiation. In particular, we consider the novel modality of phase contrast by self-interference of the X-ray wave behind an object (i.e., phase contrast by free space propagation). Using the cricket Acheta domesticus (L.) as model organism, we found that the combination of FAE fixative and iodine staining provided the best results across different tissues. The drying technique also affected contrast and prevented artifacts in specific cases. Overall, we found that for the interests of ecological studies, X-ray computed tomography is useful when the tissue or structure of interest has sufficient contrast that allows for an automatic or semiautomatic segmentation. In particular, we show that reconstruction schemes which exploit phase contrast can yield enhanced image quality. Combined with suitable specimen preparation and automated analysis, X-ray CT can therefore become a promising quantitative 3D imaging technique to study organisms' responses to environmental drivers, in both ecology and evolution.}, } @article {pmid30151183, year = {2018}, author = {Raulo, A and Dantzer, B}, title = {Associations between glucocorticoids and sociality across a continuum of vertebrate social behavior.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7697-7716}, pmid = {30151183}, issn = {2045-7758}, abstract = {The causes and consequences of individual differences in animal behavior and stress physiology are increasingly studied in wild animals, yet the possibility that stress physiology underlies individual variation in social behavior has received less attention. In this review, we bring together these study areas and focus on understanding how the activity of the vertebrate neuroendocrine stress axis (HPA-axis) may underlie individual differences in social behavior in wild animals. We first describe a continuum of vertebrate social behaviors spanning from initial social tendencies (proactive behavior) to social behavior occurring in reproductive contexts (parental care, sexual pair-bonding) and lastly to social behavior occurring in nonreproductive contexts (nonsexual bonding, group-level cooperation). We then perform a qualitative review of existing literature to address the correlative and causal association between measures of HPA-axis activity (glucocorticoid levels or GCs) and each of these types of social behavior. As expected, elevated HPA-axis activity can inhibit social behavior associated with initial social tendencies (approaching conspecifics) and reproduction. However, elevated HPA-axis activity may also enhance more elaborate social behavior outside of reproductive contexts, such as alloparental care behavior. In addition, the effect of GCs on social behavior can depend upon the sociality of the stressor (cause of increase in GCs) and the severity of stress (extent of increase in GCs). Our review shows that the while the associations between stress responses and sociality are diverse, the role of HPA-axis activity behind social behavior may shift toward more facilitating and less inhibiting in more social species, providing insight into how stress physiology and social systems may co-evolve.}, } @article {pmid30151182, year = {2018}, author = {Galloway, LF and Watson, RHB and Prendeville, HR}, title = {Response to joint selection on germination and flowering phenology depends on the direction of selection.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7688-7696}, pmid = {30151182}, issn = {2045-7758}, abstract = {Flowering and germination time are components of phenology, a complex phenotype that incorporates a number of traits. In natural populations, selection is likely to occur on multiple components of phenology at once. However, we have little knowledge of how joint selection on several phenological traits influences evolutionary response. We conducted one generation of artificial selection for all combinations of early and late germination and flowering on replicated lines within two independent base populations in the herb Campanula americana. We then measured response to selection and realized heritability for each trait. Response to selection and heritability were greater for flowering time than germination time, indicating greater evolutionary potential of this trait. Selection for earlier phenology, both flowering and germination, did not depend on the direction of selection on the other trait, whereas response to selection to delay germination and flowering was greater when selection on the other trait was in the opposite direction (e.g., early germination and late flowering), indicating a negative genetic correlation between the traits. Therefore, the extent to which correlations shaped response to selection depended on the direction of selection. Furthermore, the genetic correlation between timing of germination and flowering varies across the trait distributions. The negative correlation between germination and flowering time found when selecting for delayed phenology follows theoretical predictions of constraint for traits that jointly determine life history schedule. In contrast, the lack of constraint found when selecting for an accelerated phenology suggests a reduction of the covariance due to strong selection favoring earlier flowering and a shorter life cycle. This genetic architecture, in turn, will facilitate further evolution of the early phenology often favored in warm climates.}, } @article {pmid30151181, year = {2018}, author = {Jenkins, C and Eggleton, J and Barry, J and O'Connor, J}, title = {Advances in assessing Sabellaria spinulosa reefs for ongoing monitoring.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7673-7687}, pmid = {30151181}, issn = {2045-7758}, abstract = {Standardized and repeatable data acquisition and analyses are required to enable the mapping and condition monitoring of reefs within Marine Protected Areas (MPAs). Changes in habitat condition must be reliably identified and reported to best support evidence-based management. Biogenic reefs in temperate waters, that is, hard matter created by living organisms and raised above the seabed, provide food and shelter for many plant and animal species. This article explores the feasibility of habitat mapping, using remote sensing datasets, as well as metrics for repeatable and suitable assessment of areas of Sabellaria spinulosa for their status as biogenic reef. Data were gathered within the North Norfolk Sandbanks and Saturn Reef candidate Special Area of Conservation/Site of Community Importance in the southern North Sea. Six study areas were identified as potential locations of biogenic reef using previously acquired data, and these were targeted for further investigation using a combination of high resolution multibeam echosounder and sidescan sonar. Where potential S. spinulosa was identified from the acoustic data, a drop-down camera system was employed for visual verification. Areas of known and potential S. spinulosa reef were mapped successfully at two of the six study areas, although future approaches should take careful consideration of the seabed morphology and predominant habitat backdrop to successfully interpret such data. Camera tows from S. spinulosa reef areas were broken up into 5-s segments, with each segment scored for (a) average tube elevation; (b) average percentage cover; and (c) for the presence or absence of S. spinulosa. These metrics were utilized to create summary statistics, including a value of patchiness derived from presence/absence data, that is recommended for application as part of future monitoring programs. The application of this methodology could benefit wider assessments of similar threated or declining habitats such as intertidal Mytilus edulis beds on mixed and sandy sediments, Maerl beds, Modioulus modiolus beds, Ostrea edulis beds, and Zostera beds where patchiness may also be considered of environmental importance.}, } @article {pmid30151180, year = {2018}, author = {Rodrigues, EV and Riguette, JR and Pereira, HRC and Tesch, JA and Silva, AG}, title = {An affordable apparatus for fine-controlled emulation of buzzing frequencies of bees for the testing hypothesis in buzz interactions.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7667-7672}, pmid = {30151180}, issn = {2045-7758}, abstract = {The buzzing foraging behavior of female bees for pollen harvesting called the attention of early pollination biologists. Flower types that demand this buzzing behavior comprise about 20,000 species of different and phylogenetically unrelated plant taxa, suggesting that it had independently evolved many times among the flowering plants. Between the late 1970s and early 1980s, theoretical papers had modeled the energetics of buzz pollination, but, up to this moment, no hypothesis was experimentally tested concerning the theoretical basis of the energetics of buzz pollination. We present a cost-effective and simple apparatus, including a digital and highly accurate frequency generator, and a device for the transference of buzz-frequency energy to the receptive floral unity. The receptive floral unities may comprise the entire or partial androecium, or the tubular corolla, or, in some cases, the whole flower. This apparatus can be easily used in both laboratory and field conditions of research, as natural air currents are avoided, and the response of pollen liberation can be quantitatively measured by pollen grain counts that can be captured by adhesion in slide poured with an isosmotic lactate-glycerol media. The maximum displacement of the hardwire beam/claw system was 0.1170 ± 0.0006 mm @ 150 Hz; 0.021 ± 0.003 mm @ 250 Hz; 0.010 ± 0.001 mm @ 350 Hz; 0.0058 ± 0.0001 mm @ 450 Hz; and 0.0082 ± 0.0005 mm @ 550 Hz. Hypothesis contrasting frequency emission and pollen liberation measured as pollen grain counts may be tested in a species flower type by simple linear regression if pollen counts are normally distributed, or ordinal logistic regression, with non-normal counts. The comparison among different flower-type requirements can be tested through appropriate statistical methods for both normally and non-normally distributed pollen grain counts.}, } @article {pmid30151179, year = {2018}, author = {Palmer, DH and Tan, YQ and Finkbeiner, SD and Briscoe, AD and Monteiro, A and Kronforst, MR}, title = {Experimental field tests of Batesian mimicry in the swallowtail butterfly Papilio polytes.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7657-7666}, pmid = {30151179}, issn = {2045-7758}, support = {R01 GM108626/GM/NIGMS NIH HHS/United States ; }, abstract = {The swallowtail butterfly Papilio polytes is known for its striking resemblance in wing pattern to the toxic butterfly Pachliopta aristolochiae and is a focal system for the study of mimicry evolution. Papilio polytes females are polymorphic in wing pattern, with mimetic and nonmimetic forms, while males are monomorphic and nonmimetic. Past work invokes selection for mimicry as the driving force behind wing pattern evolution in P. polytes. However, the mimetic relationship between P. polytes and P. aristolochiae is not well understood. In order to test the mimicry hypothesis, we constructed paper replicas of mimetic and nonmimetic P. polytes and P. aristolochiae, placed them in their natural habitat, and measured bird predation on replicas. In initial trials with stationary replicas and plasticine bodies, overall predation was low and we found no differences in predation between replica types. In later trials with replicas mounted on springs and with live mealworms standing in for the butterfly's body, we found less predation on mimetic P. polytes replicas compared to nonmimetic P. polytes replicas, consistent with the predator avoidance benefits of mimicry. While our results are mixed, they generally lend support to the mimicry hypothesis as well as the idea that behavioral differences between the sexes contributed to the evolution of sexually dimorphic mimicry.}, } @article {pmid30151178, year = {2018}, author = {Barton, BT and Hodge, ME and Speights, CJ and Autrey, AM and Lashley, MA and Klink, VP}, title = {Testing the AC/DC hypothesis: Rock and roll is noise pollution and weakens a trophic cascade.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7649-7656}, pmid = {30151178}, issn = {2045-7758}, abstract = {Anthropogenic sound is increasingly considered a major environmental issue, but its effects are relatively unstudied. Organisms may be directly affected by anthropogenic sound in many ways, including interference with their ability to detect mates, predators, or food, and disturbances that directly affect one organism may in turn have indirect effects on others. Thus, to fully appreciate the net effect of anthropogenic sound, it may be important to consider both direct and indirect effects. We report here on a series of experiments to test the hypothesis that anthropogenic sound can generate cascading indirect effects within a community. We used a study system of lady beetles, soybean aphids, and soybean plants, which are a useful model for studying the direct and indirect effects of global change on food webs. For sound treatments, we used several types of music, as well as a mix of urban sounds (e.g., sirens, vehicles, and construction equipment), each at volumes comparable to a busy city street or farm tractor. In 18-hr feeding trials, rock music and urban sounds caused lady beetles to consume fewer aphids, but other types of music had no effect even at the same volume. We then tested the effect of rock music on the strength of trophic cascades in a 2-week experiment in plant growth chambers. When exposed to music by AC/DC, who articulated the null hypothesis that "rock and roll ain't noise pollution" in a song of the same name, lady beetles were less effective predators, resulting in higher aphid density and reduced final plant biomass relative to control (no music) treatments. While it is unclear what characteristics of sound generate these effects, our results reject the AC/DC hypothesis and demonstrate that altered interspecific interactions can transmit the indirect effects of anthropogenic noise through a community.}, } @article {pmid30151177, year = {2018}, author = {Dai, X and Long, C and Xu, J and Guo, Q and Zhang, W and Zhang, Z and Bater, }, title = {Are dominant plant species more susceptible to leaf-mining insects? A case study at Saihanwula Nature Reserve, China.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7633-7648}, pmid = {30151177}, issn = {2045-7758}, abstract = {Dominant species significantly affect interspecific relationships, community structure, and ecosystem function. In the field, dominant species are often identified by their high importance values. Selective foraging on dominant species is a common phenomenon in ecology. Our hypothesis is that dominant plant groups with high importance values are more susceptible to leaf-mining insects at the regional level. Here, we used the Saihanwula National Nature Reserve as a case study to examine the presence-absence patterns of leaf-mining insects on different plants in a forest-grassland ecotone in Northeast China. We identified the following patterns: (1) After phylogenetic correction, plants with high importance values are more likely to host leafminers at the species, genus, or family level. (2) Other factors including phylogenetic isolation, life form, water ecotype, and phytogeographical type of plants have different influences on the relationship between plant dominance and leafminer presence. In summary, the importance value is a valid predictor of the presence of consumers, even when we consider the effects of plant phylogeny and other plant attributes. Dominant plant groups are large and susceptible targets of leaf-mining insects. The consistent leaf-mining distribution pattern across different countries, vegetation types, and plant taxa can be explained by the "species-area relationship" or the "plant apparency hypothesis."}, } @article {pmid30151176, year = {2018}, author = {Węsławski, JM and Dragańska-Deja, K and Legeżyńska, J and Walczowski, W}, title = {Range extension of a boreal amphipod Gammarus oceanicus in the warming Arctic.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7624-7632}, pmid = {30151176}, issn = {2045-7758}, abstract = {The recent (2008-2016) occurrence of a boreal intertidal amphipod Gammarus oceanicus along the Spitsbergen coast is compared with corresponding data from 1980 to 1994. We aimed to compare the pace of environmental changes in the area (ice retreat, temperature increase) with distribution change of G. oceanicus. Material for the study was collected from intertidal, at low water level from over 100 locations on Spitsbergen, the main island of Svalbard archipelago (expanding from 76 to 80°N). The west coast of the island has been exposed to a steady increase in sea surface and air temperature (2°C in 20 years), as well as a significant decrease in fast ice duration (from over 5 months to less than 1 per year). A total length of more than 3,600 km of the island's coastline has been recently impacted by warming. Of the two sibling Gammarus species that dwell in the Spitsbergen littoral, G. setosus, the local cold water species remains generally where it was observed about 20-30 years ago. By contrast, boreal G. oceanicus has expanded its distribution range by over 1,300 km along the west and north coasts of Spitsbergen and gained dominating position on the number of sites, where it was previously just an occasional species.}, } @article {pmid30151175, year = {2018}, author = {Klaassen, B and Broekhuis, F}, title = {Living on the edge: Multiscale habitat selection by cheetahs in a human-wildlife landscape.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7611-7623}, pmid = {30151175}, issn = {2045-7758}, abstract = {Animals select habitats that will ultimately optimize their fitness through access to favorable resources, such as food, mates, and breeding sites. However, access to these resources may be limited by bottom-up effects, such as availability, and top-down effects, such as risk avoidance and competition, including that with humans. Competition between wildlife and people over resources, specifically over space, has played a significant role in the worldwide decrease in large carnivores. The goal of this study was to determine the habitat selection of cheetahs (Acinonyx jubatus) in a human-wildlife landscape at multiple spatial scales. Cheetahs are a wide-ranging, large carnivore, whose significant decline is largely attributed to habitat loss and fragmentation. It is believed that 77% of the global cheetah population ranges outside protected areas, yet little is known about cheetahs' resource use in areas where they co-occur with people. The selection, or avoidance, of three anthropogenic variables (human footprint density, distance to main roads and wildlife areas) and five environmental variables (open habitat, semiclosed habitat, edge density, patch density and slope), at multiple spatial scales, was determined by analyzing collar data from six cheetahs. Cheetahs selected variables at different scales; anthropogenic variables were selected at broader scales (720-1440 m) than environmental variables (90-180 m), suggesting that anthropogenic pressures affect habitat selection at a home-range level, whilst environmental variables influence site-level habitat selection. Cheetah presence was best explained by human presence, wildlife areas, semiclosed habitat, edge density and slope. Cheetahs showed avoidance for humans and steep slopes and selected for wildlife areas and areas with high proportions of semiclosed habitat and edge density. Understanding a species' resource requirements, and how these might be affected by humans, is crucial for conservation. Using a multiscale approach, we provide new insights into the habitat selection of a large carnivore living in a human-wildlife landscape.}, } @article {pmid30151174, year = {2018}, author = {Czenze, ZJ and Tucker, JL and Clare, EL and Littlefair, JE and Hemprich-Bennett, D and Oliveira, HFM and Brigham, RM and Hickey, AJR and Parsons, S}, title = {Spatiotemporal and demographic variation in the diet of New Zealand lesser short-tailed bats (Mystacina tuberculata).}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7599-7610}, pmid = {30151174}, issn = {2045-7758}, abstract = {Variation in the diet of generalist insectivores can be affected by site-specific traits including weather, habitat, and season, as well as demographic traits such as reproductive status and age. We used molecular methods to compare diets of three distinct New Zealand populations of lesser short-tailed bats, Mystacina tuberculata. Summer diets were compared between a southern cold-temperate (Eglinton) and a northern population (Puroera). Winter diets were compared between Pureora and a subtropical offshore island population (Hauturu). This also permitted seasonal diet comparisons within the Pureora population. Lepidoptera and Diptera accounted for >80% of MOTUs identified from fecal matter at each site/season. The proportion of orders represented within prey and the Simpson diversity index, differed between sites and seasons within the Pureora population. For the Pureora population, the value of the Simpson diversity index was higher in summer than winter and was higher in Pureora compared to Eglinton. Summer Eglinton samples revealed that juvenile diets appeared to be more diverse than other demographic groups. Lactating females had the lowest dietary diversity during summer in Pureora. In Hauturu, we found a significant negative relationship between mean ambient temperature and prey richness. Our data suggest that M. tuberculata incorporate a narrower diversity of terrestrial insects than previously reported. This provides novel insights into foraging behavior and ecological interactions within different habitats. Our study is the first from the Southern Hemisphere to use molecular techniques to examine spatiotemporal variation in the diet of a generalist insectivore that inhabits a contiguous range with several habitat types and climates.}, } @article {pmid30151173, year = {2018}, author = {Poidatz, J and Monceau, K and Bonnard, O and Thiéry, D}, title = {Activity rhythm and action range of workers of the invasive hornet predator of honeybees Vespa velutina, measured by radio frequency identification tags.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7588-7598}, pmid = {30151173}, issn = {2045-7758}, abstract = {In social insects, the activity rhythm of foragers and their action range determinate the activity of the colony. In vespids, which are mostly predators, the foraging range of workers determines their maximum predation pressure round the nest. One of these species, Vespa velutina, a recently invasive species introduced into Europe, exerts a strong predation on honeybees at the hive. Therefore, the definition of its activity rhythm and spatial range of predation is of primary importance. Using radio frequency identification tags (RFID), two experiments were carried out to (a) determine their return ability (called homing) in releasing 318 individuals at different distance from their colony and (b) monitor their foraging activity rhythm and the duration of their flights based on 71 individuals followed 24 hr/24 during 2 months. The homing ability of V. velutina was evaluated to be up to 5,000 m and was not affected by the cardinal orientation of release point. The lag time to return to the nest increased with the distance of release. Most of the flight activity took place between 07:00 a.m. and 08:00 p.m., hornets doing principally short flights of less than an hour. Foraging range was thus estimated ca. 1,000 m around the nest. This study of V. velutina assisted by RFID tags provides for the first time a baseline for its potential foraging distance that increase our knowledge of this species to (a) refine more accurately models for risk assessment and (b) define security perimeter for early detection of predation on invasion front.}, } @article {pmid30151172, year = {2018}, author = {Gresty, CEA and Clare, E and Devey, DS and Cowan, RS and Csiba, L and Malakasi, P and Lewis, OT and Willis, KJ}, title = {Flower preferences and pollen transport networks for cavity-nesting solitary bees: Implications for the design of agri-environment schemes.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7574-7587}, pmid = {30151172}, issn = {2045-7758}, abstract = {Floral foraging resources are valuable for pollinator conservation on farmland, and their provision is encouraged by agri-environment schemes in many countries. Across Europe, wildflower seed mixtures are widely sown on farmland to encourage pollinators, but the extent to which key pollinator groups such as solitary bees exploit and benefit from these resources is unclear. We used high-throughput sequencing of 164 pollen samples extracted from the brood cells of six common cavity-nesting solitary bee species (Osmia bicornis, Osmia caerulescens, Megachile versicolor, Megachile ligniseca, Megachile centuncularis and Hylaeus confusus) which are widely distributed across the UK and Europe. We documented their pollen use across 19 farms in southern England, UK, revealing their forage plants and examining the structure of their pollen transport networks. Of the 32 plant species included currently in sown wildflower mixes, 15 were recorded as present within close foraging range of the bees on the study farms, but only Ranunculus acris L. was identified within the pollen samples. Rosa canina L. was the most commonly found of the 23 plant species identified in the pollen samples, suggesting that, in addition to providing a nesting resource for Megachile leafcutter bees, it may be an important forage plant for these species. Higher levels of connectance and nestedness were characteristic of pollen transport networks on farms with abundant floral resources, which may increase resilience to species loss. Our data suggest that plant species promoted currently by agri-environment schemes are not optimal for solitary bee foraging. If a diverse community of pollinators is to be supported on UK and European farmland, additional species such as R. canina should be encouraged to meet the foraging requirements of solitary bees.}, } @article {pmid30151171, year = {2018}, author = {Derua, YA and Kahindi, SC and Mosha, FW and Kweka, EJ and Atieli, HE and Wang, X and Zhou, G and Lee, MC and Githeko, AK and Yan, G}, title = {Microbial larvicides for mosquito control: Impact of long lasting formulations of Bacillus thuringiensis var. israelensis and Bacillus sphaericus on non-target organisms in western Kenya highlands.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7563-7573}, pmid = {30151171}, issn = {2045-7758}, support = {D43 TW001505/TW/FIC NIH HHS/United States ; R01 AI050243/AI/NIAID NIH HHS/United States ; U19 AI129326/AI/NIAID NIH HHS/United States ; }, abstract = {The microbial larvicides Bacillus thuringiensis var. israelensis and Bacillus sphaericus have been used extensively for mosquito control and have been found to be effective and safe to non-target organisms cohabiting with mosquito larvae. Recently developed long lasting microbial larvicides (LLML), although evading the previous challenge of short duration of activity, increase the risk of persistence of toxins in the treated larval habitats. This study monitored the impact of LLML FourStar® and LL3 on non-target organisms cohabiting with mosquito larvae in an operational study to control malaria vectors in western Kenya highlands. A total of 300 larval habitats were selected in three highland villages. The habitats were first monitored for 5 weeks to collect baseline data on non-target organisms cohabiting with mosquito larvae and then randomized into two treatment arms (respective FourStar® and LL3) and one control arm. Non-target organisms were sampled weekly for 5 months after treatment to assess the impact of LLML intervention. Before treatment, the mean density of all non-target organisms combined in the control, LL3 and FourStar® treated habitats was 1.42, 1.39 and 1.49 individuals per habitat per sampling occasion, respectively. Following treatment, this density remained fairly unchanged for 21 weeks at which time it was 1.82, 2.11, and 2.05 for the respective control, LL3 and FourStar® treated habitats. Statistical analysis revealed that LL3 and FourStar® did not significantly alter abundance, richness or diversity of the 11 taxa studied, when comparing the intervention and control larval habitats. However, both FourStar® and LL3 significantly reduced the density of malaria vectors. In conclusion, one round of label rate application of FourStar® or LL3 in natural larval habitats did not alter richness, abundance or diversity of the monitored aquatic non-target organisms cohabiting with mosquito larvae to an ecologically significant level.}, } @article {pmid30151170, year = {2018}, author = {Grant, EHC and Brand, AB and De Wekker, SFJ and Lee, TR and Wofford, JEB}, title = {Evidence that climate sets the lower elevation range limit in a high-elevation endemic salamander.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7553-7562}, pmid = {30151170}, issn = {2045-7758}, abstract = {A frequent assumption in ecology is that biotic interactions are more important than abiotic factors in determining lower elevational range limits (i.e., the "warm edge" of a species distribution). However, for species with narrow environmental tolerances, theory suggests the presence of a strong environmental gradient can lead to persistence, even in the presence of competition. The relative importance of biotic and abiotic factors is rarely considered together, although understanding when one exerts a dominant influence on controlling range limits may be crucial to predicting extinction risk under future climate conditions. We sampled multiple transects spanning the elevational range limit of Plethodon shenandoah and site and climate covariates were recorded. A two-species conditional occupancy model, accommodating heterogeneity in detection probability, was used to relate variation in occupancy with environmental and habitat conditions. Regional climate data were combined with datalogger observations to estimate the cloud base heights and to project future climate change impacts on cloud elevations across the survey area. By simultaneously accounting for species' interactions and habitat variables, we find that elevation, not competition, is strongly correlated with the lower elevation range boundary, which had been presumed to be restricted mainly as a result of competitive interactions with a congener. Because the lower elevational range limit is sensitive to climate variables, projected climate change across its high-elevation habitats will directly affect the species' distribution. Testing assumptions of factors that set species range limits should use models which accommodate detection biases.}, } @article {pmid30151169, year = {2018}, author = {Ołdakowski, Ł and Taylor, JRE}, title = {Oxidative damage and antioxidant defense are assay and tissue-dependent both in captive and wild-caught bank voles (Myodes glareolus) before and after reproduction.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7543-7552}, pmid = {30151169}, issn = {2045-7758}, abstract = {Reproduction is costly and life-history theory predicts that current parental investment will result in lower survival or decreased future reproduction. The physiological mechanisms mediating the link between reproduction and survival are still under debate and elevated oxidative damage during reproduction has been proposed as a plausible candidate. Previous studies of oxidative stress during reproduction in animals under natural conditions have been restricted to analyses of blood. Herein, we measured the level of oxidative damage to lipids (tiobarbituric-acid-reactive substances) and proteins (carbonyls) in the liver, kidneys, heart and skeletal muscles in free-living bank vole females from spring and autumn generations, before and after reproduction. Antioxidant defense in the liver and kidneys was also determined. We expected oxidative damage to tissues and hypothesized that the damage would be more uniform between tissues in wild animals compared to those breeding under laboratory conditions. Considering all combinations of markers/tissues/generations, oxidative damage in females did not differ before and after reproduction in 12 comparisons, was lower after reproduction in three comparisons, and was higher after breeding in one comparison. The total glutathione was significantly increased after reproduction only in the liver of the autumn generation and there was no change in catalase activity. Our results confirm-for the first time in the field-previous observations from laboratory studies that there is no simple link between oxidative stress and reproduction and that patterns depend on the tissue and marker being studied. Overall, however, our study does not support the hypothesis that the cost of reproduction in bank voles is mediated by oxidative stress in these tissues.}, } @article {pmid30151168, year = {2018}, author = {Enners, L and Schwemmer, P and Corman, AM and Voigt, CC and Garthe, S}, title = {Intercolony variations in movement patterns and foraging behaviors among herring gulls (Larus argentatus) breeding in the eastern Wadden Sea.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7529-7542}, pmid = {30151168}, issn = {2045-7758}, abstract = {Herring gulls (Larus argentatus) are opportunistic predators that prefer to forage in the intertidal zone, but an increasing degree of terrestrial foraging has recently been observed. We therefore aimed to analyze the factors influencing foraging behavior and diet composition in the German Wadden Sea. Gulls from three breeding colonies on islands at different distances from the mainland were equipped with GPS data loggers during the incubation seasons in 2012-2015. Logger data were analyzed for 37 individuals, including 1,115 foraging trips. Herring gulls breeding on the island furthest from the mainland had shorter trips (mean total distance = 12.3 km; mean maximum distance = 4.2 km) and preferred to feed on the tidal flats close to the colony, mainly feeding on common cockles (Cerastoderma edule) and shore crabs (Carcinus maenas). In contrast, herring gulls breeding close to the mainland carried out trips with a mean total distance of 26.7 km (mean maximum distance = 9.2 km). These gulls fed on the neobiotic razor clams (Ensis leei) in the intertidal zone, and a larger proportion of time was spent in distant terrestrial habitats on the mainland, feeding on earthworms. δ13C and δ15N values were higher at the colony furthest from the mainland and confirmed a geographical gradient in foraging strategy. Analyses of logger data, pellets, and stable isotopes revealed that herring gulls preferred to forage in intertidal habitats close to the breeding colony, but shifted to terrestrial habitats on the mainland as the tide rose and during the daytime. Reduced prey availability in the vicinity of the breeding colony might force herring gulls to switch to feed on razor clams in the intertidal zone or to use distant terrestrial habitats. Herring gulls may thus act as an indicator for the state of the intertidal system close to their breeding colony.}, } @article {pmid30151167, year = {2018}, author = {Hattori, RS and Tashiro, S and Zhang, Y and Kakuta, N and Yokota, M and Strüssmann, CA and Yamamoto, Y}, title = {Demonstration of viability and fertility and development of a molecular tool to identify YY supermales in a fish with both genotypic and environmental sex determination.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7522-7528}, pmid = {30151167}, issn = {2045-7758}, abstract = {The pejerrey possesses a genotypic sex determination system driven by the amhy gene and yet shows marked temperature-dependent sex determination. Sex-reversed XY females have been found in a naturally breeding population established in Lake Kasumigaura, Japan. These females could mate with normal XY males and generate YY "supermale" individuals that, if viable and fertile, would sire only genotypic male offspring. This study was conducted to verify the viability, gender, and fertility of YY pejerrey and to develop a molecular method for their identification. Production of YY fish was attempted by crossing a thermally sex-reversed XY female and an XY male, and rearing the progeny until sexual maturation. To identify the presumable YY individuals, we first conducted a PCR analysis using amhy-specific primers to screen only amhy-positive (XY and YY) fish. This screening showed that 60.6% of the progeny was amhy-positive, which suggested the presence of YY fish. We then conducted a second screening by qPCR in order to identify the individuals with two amhy copies in their genome. This screening revealed 13 individuals, all males, with values twice higher than the other 30 amhy-positive fishes, suggesting they have a YY complement. This assumption as well as the viability, fertility, and "supermale" nature of these individuals was confirmed in progeny tests with XX females that yielded 100% amhy-positive offspring. These results demonstrate that qPCR can obviate progeny test as a means to identify the genotypic sex and therefore may be useful for the survey of all three possible genotypes in wild populations.}, } @article {pmid30151166, year = {2018}, author = {King, RB and Stanford, KM and Jones, PC}, title = {Sunning themselves in heaps, knots, and snarls: The extraordinary abundance and demography of island watersnakes.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7500-7521}, pmid = {30151166}, issn = {2045-7758}, abstract = {Snakes represent a sizable fraction of vertebrate biodiversity, but until recently, data on their demography have been sparse. Consequently, generalizations regarding patterns of variation are weak and the potential for population projections is limited. We address this information gap through an analysis of spatial and temporal variation in demography (population size, annual survival, and realized population growth) of the Lake Erie Watersnake, Nerodia sipedon insularum, and a review of snake survival more generally. Our study spans a period during which the Lake Erie Watersnake was listed as threatened under the U.S. Endangered Species Act, recovered, and was delisted. We collected capture-mark-recapture data at 14 study sites over 20 years, accruing 20,000 captures of 13,800 individually marked adults. Lake Erie Watersnakes achieve extraordinary abundance, averaging 520 adults per km of shoreline (ca. 260 adult per ha) at our study sites (range = 160-1,600 adults per km; ca. 80-800 adults per ha) and surpassing population recovery and postdelisting monitoring criteria. Annual survival averages 0.68 among adult females and 0.76 among adult males, varies among sites, and is positively correlated with body size among study sites. Temporal process variance in annual survival is low, averaging 0.0011 or less than 4% of total variance; thus, stochasticity in annual survival may be of minor significance to snake extinction risk. Estimates of realized population growth indicate that population size has been stable or increasing over the course of our study. More generally, snake annual survival overlaps broadly across continents, climate zones, families, subfamilies, reproductive modes, body size categories, maturation categories, and parity categories. Differences in survival in relation to size, parity, and maturation are in the directions predicted by life history theory but are of small magnitude with much variation around median values. Overall, annual survival appears to be quite plastic, varying with food availability, habitat quality, and other ecological variables.}, } @article {pmid30151165, year = {2018}, author = {Bosque, RJ and Lawrence, JP and Buchholz, R and Colli, GR and Heppard, J and Noonan, B}, title = {Diversity of warning signal and social interaction influences the evolution of imperfect mimicry.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7490-7499}, pmid = {30151165}, issn = {2045-7758}, abstract = {Mimicry, the resemblance of one species by another, is a complex phenomenon where the mimic (Batesian mimicry) or the model and the mimic (Mullerian mimicry) gain an advantage from this phenotypic convergence. Despite the expectation that mimics should closely resemble their models, many mimetic species appear to be poor mimics. This is particularly apparent in some systems in which there are multiple available models. However, the influence of model pattern diversity on the evolution of mimetic systems remains poorly understood. We tested whether the number of model patterns a predator learns to associate with a negative consequence affects their willingness to try imperfect, novel patterns. We exposed week-old chickens to coral snake (Micrurus) color patterns representative of three South American areas that differ in model pattern richness, and then tested their response to the putative imperfect mimetic pattern of a widespread species of harmless colubrid snake (Oxyrhopus rhombifer) in different social contexts. Our results indicate that chicks have a great hesitation to attack when individually exposed to high model pattern diversity and a greater hesitation to attack when exposed as a group to low model pattern diversity. Individuals with a fast growth trajectory (measured by morphological traits) were also less reluctant to attack. We suggest that the evolution of new patterns could be favored by social learning in areas of low pattern diversity, while individual learning can reduce predation pressure on recently evolved mimics in areas of high model diversity. Our results could aid the development of ecological predictions about the evolution of imperfect mimicry and mimicry in general.}, } @article {pmid30151164, year = {2018}, author = {Abbott, JM and DuBois, K and Grosberg, RK and Williams, SL and Stachowicz, JJ}, title = {Genetic distance predicts trait differentiation at the subpopulation but not the individual level in eelgrass, Zostera marina.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7476-7489}, pmid = {30151164}, issn = {2045-7758}, abstract = {Ecological studies often assume that genetically similar individuals will be more similar in phenotypic traits, such that genetic diversity can serve as a proxy for trait diversity. Here, we explicitly test the relationship between genetic relatedness and trait distance using 40 eelgrass (Zostera marina) genotypes from five sites within Bodega Harbor, CA. We measured traits related to nutrient uptake, morphology, biomass and growth, photosynthesis, and chemical deterrents for all genotypes. We used these trait measurements to calculate a multivariate pairwise trait distance for all possible genotype combinations. We then estimated pairwise relatedness from 11 microsatellite markers. We found significant trait variation among genotypes for nearly every measured trait; however, there was no evidence of a significant correlation between pairwise genetic relatedness and multivariate trait distance among individuals. However, at the subpopulation level (sites within a harbor), genetic (FST) and trait differentiation were positively correlated. Our work suggests that pairwise relatedness estimated from neutral marker loci is a poor proxy for trait differentiation between individual genotypes. It remains to be seen whether genomewide measures of genetic differentiation or easily measured "master" traits (like body size) might provide good predictions of overall trait differentiation.}, } @article {pmid30151163, year = {2018}, author = {Brancalion, PHS and Oliveira, GCX and Zucchi, MI and Novello, M and van Melis, J and Zocchi, SS and Chazdon, RL and Rodrigues, RR}, title = {Phenotypic plasticity and local adaptation favor range expansion of a Neotropical palm.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7462-7475}, pmid = {30151163}, issn = {2045-7758}, abstract = {One of the most intriguing questions in plant ecology is which evolutionary strategy allows widely distributed species to increase their ecological range and grow in changing environmental conditions. Phenotypic plasticity and local adaptations are major processes governing species range margins, but little is known about their relative contribution for tree species distribution in tropical forest regions. We investigated the relative role of phenotypic plasticity and local adaptation in the ecological distribution of the widespread palm Euterpe edulis in the Brazilian Atlantic Forest. Genetic sampling and experiments were performed in old-growth remnants of two forest types with higher (Seasonal Semideciduous Forests vs. Submontane Rainforest) and lower biogeographic association and environmental similarities (Submontane Rainforest vs. Restinga Forest). We first assessed the molecular genetic differentiation among populations, focusing on the group of loci potentially under selection in each forest, using single-nucleotide polymorphism (SNPs) outliers. Further, we looked for potential adaptive divergence among populations in a common garden experiment and in reciprocal transplants for two plant development phases: seedling establishment and sapling growth. Analysis with outlier loci indicated that all individuals from the Semideciduous Forest formed a single group, while another group was formed by overlapping individuals from Submontane Rainforest and Restinga Forest. Molecular differentiation was corroborated by reciprocal transplants, which yielded strong evidence of local adaptations for seedling establishment in the biogeographically divergent Rainforest and Semideciduous Forest, but not for Restinga Forest and Submontane Rainforest. Phenotypic plasticity for palm seedling establishment favors range expansion to biogeographically related or recently colonized forest types, while persistence in the newly colonized ecosystem may be favored by local adaptations if climatic conditions diverge over time, reducing gene flow between populations. SNPs obtained by next-generation sequencing can help exploring adaptive genetic variation in tropical trees, which impose several challenges to the use of reciprocal transplants.}, } @article {pmid30151162, year = {2018}, author = {Wang, K and Hu, D and Deng, J and Shangguan, Z and Deng, L}, title = {Biomass carbon storages and carbon sequestration potentials of the Grain for Green Program-Covered Forests in China.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7451-7461}, pmid = {30151162}, issn = {2045-7758}, abstract = {The Grain for Green Program (GGP) was the most all-embracing program of ecological reconstruction implemented in China. To estimate carbon storages and carbon sequestration potentials of the GGP forests, the study presented in the paper collected data spanning from 1999 to 2010, such as tree species, tree planting area relevant to the GGP, empirical growth curves suitable for different planted tree species in China, as well as wood density (WD), biomass expansion factor (BEF), carbon fraction (CF) of different trees species, and estimated the carbon storages of the biomasses of GGP forests from 1999 to 2050. It showed that the total carbon storage of the biomass of GGP forests was 320.29 Tg upon the GGP completion in 2010; the total carbon sequestration is higher during the early GGP-implementation stage than at the late GGP-implementation stage, and the annual mean carbon sequestration of GGP forests was 26.69 Tg/year. The potential of GGP forests as carbon sink presented an increasing increment. In China, the potential increments of GGP forests as carbon sinks were estimated to be 397.34, 604.00, 725.53, and 808.90 Tg in 2020, 2030, 2040, and 2050, respectively, and the carbon sequestration rates were 1.72, 0.89, 0.52, and 0.36 Mg ha-1 year-1, respectively, corresponding to 2010s, 2020s, 2030s, and 2040s. Therefore, the GGP forests had bigger carbon sequestration capacities and potentials in China.}, } @article {pmid30151161, year = {2018}, author = {Jiang, Y and Wang, T and Wu, Y and Hu, R and Huang, K and Shao, X}, title = {Past distribution of epiphyllous liverworts in China: The usability of historical data.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7436-7450}, pmid = {30151161}, issn = {2045-7758}, abstract = {Epiphyllous liverworts form a special group of bryophytes that primarily grow on the leaves of understory vascular plants in tropical and subtropical evergreen broadleaf forests. Being sensitive to moisture and temperature changes, epiphyllous liverworts are often considered to be good indicators of climate change and forest degradation. However, they are a poorly collected and taxonomically complicated group, with an only partly identified distribution pattern. In this study, we built four models based on 24 environmental variables at four different spatial resolutions (i.e., 1 km, 5 km, 10 km, and 15 km) to predict the past distribution of epiphyllous liverworts in China, using Maxent model and 63 historical location records (i.e., presence-only data). Both area under the curve of the receiver operating characteristic (AUC) and true skill statistic (TSS) methods are used to assess the model performance. Results showed that the model with the predictors at a 15-km resolution achieved the highest predictive accuracy (AUC=0.946; TSS=0.880), although there was no statistically significant difference between the four models (p > 0.05). The most significant environmental variables included aridity, annual precipitation, precipitation of wettest month, precipitation of wettest quarter, and precipitation of warmest quarter, annual mean NDVI, and minimum NDVI. The predicted suitable areas for epiphyllous liverworts were mainly located in the south of Yangtze River and seldom exceed 35°N, which were consistent with the museum and herbarium records, as well as the historical records in scientific literatures. Our study further demonstrated the value of historical data to ecological and evolutionary studies.}, } @article {pmid30151160, year = {2018}, author = {Coryell, RL and Turnham, KE and de Jesus Ayson, EG and Lavilla-Pltogo, C and Alcala, AC and Sotto, F and Gonzales, B and Nishiguchi, MK}, title = {Phylogeographic patterns in the Philippine archipelago influence symbiont diversity in the bobtail squid-Vibrio mutualism.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7421-7435}, pmid = {30151160}, issn = {2045-7758}, support = {K12 GM088021/GM/NIGMS NIH HHS/United States ; }, abstract = {Marine microbes encounter a myriad of biotic and abiotic factors that can impact fitness by limiting their range and capacity to move between habitats. This is especially true for environmentally transmitted bacteria that cycle between their hosts and the surrounding habitat. As geologic history, biogeography, and other factors such as water temperature, salinity, and physical barriers can inhibit bacterial movement to novel environments, we chose to examine the genetic architecture of Euprymna albatrossae (Mollusca: Cephalopoda) and their Vibrio fischeri symbionts in the Philippine archipelago using a combined phylogeographic approach. Eleven separate sites in the Philippine islands were examined using haplotype estimates that were examined via nested clade analysis to determine the relationship between E. albatrossae and V. fischeri populations and their geographic location. Identical analyses of molecular variance (AMOVA) were used to estimate variation within and between populations for host and symbiont genetic data. Host animals demonstrated a significant amount of variation within island groups, while symbiont variation was found within individual populations. Nested clade phylogenetic analysis revealed that hosts and symbionts may have colonized this area at different times, with a sudden change in habitat. Additionally, host data indicate restricted gene flow, whereas symbionts show range expansion, followed by periodic restriction to genetic flow. These differences between host and symbiont networks indicate that factors "outside the squid" influence distribution of Philippine V. fischeri. Our results shed light on how geography and changing environmental factors can impact marine symbiotic associations at both local and global scales.}, } @article {pmid30151159, year = {2018}, author = {Cazzolla Gatti, R and Dudko, A and Lim, A and Velichevskaya, AI and Lushchaeva, IV and Pivovarova, AV and Ventura, S and Lumini, E and Berruti, A and Volkov, IV}, title = {The last 50 years of climate-induced melting of the Maliy Aktru glacier (Altai Mountains, Russia) revealed in a primary ecological succession.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7401-7420}, pmid = {30151159}, issn = {2045-7758}, abstract = {In this article, we report and discuss the results obtained from a survey of plants, microorganisms (bacteria and fungi), and soil elements along a chronosequence in the first 600 m of the Maliy Aktru glacier's forefront (Altai Mountains, Russia). Many glaciers of the world show effects of climate change. Nonetheless, except for some local reports, the ecological effects of deglaciation have been poorly studied and have not been quantitatively assessed in the Altai Mountains. Here, we studied the ecological changes of plants, fungi, bacteria, and soil elements that take the form of a primary ecological succession and that took place over the deglaciated soil of the Maliy Aktru glacier during the last 50 year. According to our measurements, the glacier lost about 12 m per year during the last 50 years. Plant succession shows clear signs of changes along the incremental distance from the glacier forefront. The analysis of the plant α- and β-diversity confirmed an expected increase of them with increasing distance from the glacier forefront. Moreover, the analysis of β-diversity confirmed the hypothesis of the presence of three main stages of the plant succession: (a) initial (pioneer species) from 30 to 100 m; (b) intermediate (r-selected species) from 110 to 120-150 m; and (c) final (K-selected species) from 150 to 550. Our study also shows that saprotrophic communities of fungi are widely distributed in the glacier retreating area with higher relative abundances of saprotroph ascomycetes at early successional stages. The evolution of a primary succession is also evident for bacteria, soil elements, and CO 2 emission and respiration. The development of biological communities and the variation in geochemical parameters represent an irrefutable proof that climate change is altering soils that have been long covered by ice.}, } @article {pmid30151158, year = {2018}, author = {Álvarez-Presas, M and Mateos, E and Riutort, M}, title = {Hidden diversity in forest soils: Characterization and comparison of terrestrial flatworm's communities in two national parks in Spain.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7386-7400}, pmid = {30151158}, issn = {2045-7758}, abstract = {Terrestrial flatworms (Platyhelminthes, Tricladida, and Geoplanidae) belong to what is known as cryptic soil fauna of humid forests and are animals not easily found or captured in traps. Nonetheless, they have been demonstrated to be good indicators of the conservation status of their habitat as well as a good model to reconstruct the recent and old events affecting biodiversity. This is mainly due to their delicate constitution, their dependence on the integrity of their habitat, and their very low dispersal capacity. At present, little is known about their communities, except for some studies performed in Brazil. In this work, we analyze for the first time in Europe terrestrial flatworm communities. We have selected two protected areas belonging to the Red Española de Parques Nacionales. Our aims include performing a first study of the species richness and community structure for European terrestrial planarian species at regional and local scale. We evaluate the effect of type of forests in the community composition and flatworms' abundance, but also have into account the phylogenetic framework (never considered in previous studies) analyzed based on molecular data. We find differences in the species composition among parks, with an astonishingly high diversity of endemic species in the Parque Nacional de Picos de Europa and an extremely low diversity of species in the Parque Nacional de Ordesa y Monte Perdido. These divergent patterns cannot be attributed to differences in physical variables, and in addition, the analyses of their phylogenetic relationships and, for a few species, their genetic structure, point to a more probable historical explanation.}, } @article {pmid30151157, year = {2018}, author = {Montesinos, D and Callaway, RM}, title = {Traits correlate with invasive success more than plasticity: A comparison of three Centaurea congeners.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7378-7385}, pmid = {30151157}, issn = {2045-7758}, abstract = {The importance of phenotypic plasticity for successful invasion by exotic plant species has been well studied, but with contradictory and inconclusive results. However, many previous studies focused on comparisons of native and invasive species that co-occur in a single invaded region, and thus on species with potentially very different evolutionary histories. We took a different approach by comparing three closely related Centaurea species: the highly invasive C. solstitialis, and the noninvasive but exotic C. calcitrapa and C. sulphurea. These species have overlapping distributions both in their native range of Spain and in their non-native range of California. We collected seeds from 3 to 10 populations from each region and species and grew them in common garden greenhouse conditions to obtain an F1 generation in order to reduce maternal effects. Then, F1 seeds were grown subjected to simulated herbivory, variation in nutrient availability, and competition, to explore plasticity in the responses to these conditions. We found little variation in phenotypic plasticity among species and regions, but C. solstitialis plants from California produced more biomass in competition than their Spanish conspecifics. This species also had the highest relative growth rates when in competition and when grown under low nutrient availability. Noninvasive congeners produced intermediate or opposite patterns.}, } @article {pmid30151156, year = {2018}, author = {White, HJ and Montgomery, WI and Storchová, L and Hořák, D and Lennon, JJ}, title = {Does functional homogenization accompany taxonomic homogenization of British birds and how do biotic factors and climate affect these processes?.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7365-7377}, pmid = {30151156}, issn = {2045-7758}, abstract = {Environmental change has reshuffled communities often causing taxonomic homogenization rather than differentiation. Some studies suggest that this increasing similarity of species composition between communities is accompanied by an increase in similarity of trait composition-functional homogenization-although different methodologies have failed to come to any consistent conclusions. Functional homogenization could have a large effect on ecosystem functioning and stability. Here, we use the general definition of homogenization as "reduced spatial turnover over time" to compare changes in Simpson's beta diversity (taxonomic turnover) with changes in Rao's quadratic entropy beta diversity (functional turnover) in British breeding birds at three spatial scales. Using biotic and climatic variables, we identify which factors may predispose a site to homogenization. The change in turnover measures between two time periods, 20 years apart, was calculated. A null model approach was taken to identify occurrences of functional homogenization and differentiation independent of changes in taxonomic turnover. We used conditional autoregressive models fitted using integrated nested Laplace approximations to determine how environmental drivers and factors relating to species distributions affect changes in spatial turnover of species and functional diversity. The measurement of functional homogenization affects the chance of rejection of the null models, with many sites showing taxonomic homogenization unaccompanied by functional homogenization, although occurrence varies with spatial scale. At the smallest scale, while temperature-related variables drive changes in taxonomic turnover, changes in functional turnover are associated with variation in growing degree days; however, changes in functional turnover become more difficult to predict at larger spatial scales. Our results highlight the multifactorial processes underlying taxonomic and functional homogenization and that redundancy in species traits may allow ecosystem functioning to be maintained in some areas despite changes in species composition.}, } @article {pmid30151155, year = {2018}, author = {Visser, B and Hance, T and Noël, C and Pels, C and Kimura, MT and Stökl, J and Geuverink, E and Nieberding, CM}, title = {Variation in lipid synthesis, but genetic homogeneity, among Leptopilina parasitic wasp populations.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7355-7364}, pmid = {30151155}, issn = {2045-7758}, abstract = {Lipid synthesis can have a major effect on survival and reproduction, yet most insect parasitoids fail to synthesize lipids. For parasitic wasps in the genus Leptopilina, however, studies have suggested that there is intraspecific variation in the ability for lipid synthesis. These studies were performed on only few populations, and a large-scale investigation of both lipogenic ability and population genetic structure is now needed. Here, we first examined lipogenic ability of nine Leptopilina heterotoma populations collected in 2013 and found that five of nine populations synthesized lipids. The 2013 populations could not be used to determine genetic structure; hence, we obtained another 20 populations in 2016 that were tested for lipogenic ability. Thirteen of 20 populations (all Leptopilina heterotoma) were then used to determine the level of genetic differentiation (i.e., haplotype and nucleotide diversity) by sequencing neutral mitochondrial (COI) and nuclear (ITS2) markers. None of the 2016 populations synthesized lipids, and no genetic differentiation was found. Our results did reveal a nearly twofold increase in mean wasp lipid content at emergence in populations obtained in 2016 compared to 2013. We propose that our results can be explained by plasticity in lipid synthesis, where lipogenic ability is determined by environmental factors, such as developmental temperature and/or the amount of lipids carried over from the host.}, } @article {pmid30151154, year = {2018}, author = {Wilson, TL and Schmidt, JH and Mangipane, BA and Kolstrom, R and Bartz, KK}, title = {Nest use dynamics of an undisturbed population of bald eagles.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7346-7354}, pmid = {30151154}, issn = {2045-7758}, abstract = {Management or conservation targets based on demographic rates should be evaluated within the context of expected population dynamics of the species of interest. Wild populations can experience stable, cyclical, or complex dynamics, therefore undisturbed populations can provide background needed to evaluate programmatic success. Many raptor species have recovered from large declines caused by environmental contaminants, making them strong candidates for ongoing efforts to understand population dynamics and ecosystem processes in response to human-caused stressors. Dynamic multistate occupancy models are a useful tool for analyzing species dynamics because they leverage the autocorrelation inherent in long-term monitoring datasets to obtain useful information about the dynamic properties of population or reproductive states. We analyzed a 23-year bald eagle monitoring dataset in a dynamic multistate occupancy modeling framework to assess long-term nest occupancy and reproduction in Lake Clark National Park and Preserve, Alaska. We also used a hierarchical generalized linear model to understand changes in nest productivity in relation to environmental factors. Nests were most likely to remain in the same nesting state between years. Most notably, successful nests were likely to remain in use (either occupied or successful) and had a very low probability of transitioning to an unoccupied state in the following year. There was no apparent trend in the proportion of nests used by eagles through time, and the probability that nests transitioned into or out of the successful state was not influenced by temperature or salmon availability. Productivity was constant over the course of the study, although warm April minimum temperatures were associated with increased chick production. Overall our results demonstrate the expected nesting dynamics of a healthy bald eagle population that is largely free of human disturbance and can be used as a baseline for the expected dynamics for recovering bald eagle populations in the contiguous 48 states.}, } @article {pmid30151153, year = {2018}, author = {Drever, MC and Smith, AC and Venier, LA and Sleep, DJH and MacLean, DA}, title = {Cross-scale effects of spruce budworm outbreaks on boreal warblers in eastern Canada.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7334-7345}, pmid = {30151153}, issn = {2045-7758}, abstract = {Insect outbreaks are major natural disturbance events that affect communities of forest birds, either directly by affecting the food supply or indirectly by changing the vegetation composition of forest canopies. An examination of correlations between measures of bird and insect abundance across different spatial scales and over varying time lag effects may provide insight into underlying mechanisms. We developed a hierarchical Bayesian model to assess correlations between counts of eight warbler species from the Breeding Bird Survey in eastern Canada, 1966 to 2009, with the presence of spruce budworm (Choristoneura fumiferana Clem.) at immediate local scales and time-lagged regional scales, as measured by extent of defoliation on host tree species. Budworm-associated species Cape May warbler (Setophaga tigrina), bay-breasted warbler (Setophaga castanea), and Tennessee warbler (Oreothlypis peregrina) responded strongly and positively to both local and regional effects. In contrast, non-budworm-associated species, Blackburnian warbler (Setophaga fusca), magnolia warbler (Setophaga magnolia), Canada warbler (Cardellina canadensis), black-throated blue warbler (Setophaga caerulescens), and black-throated green warbler (Setophaga virens), only responded to regional effects in a manner that varied across eastern Canada. The complex responses by forest birds to insect outbreaks involve both increased numerical responses to food supply and to longer term responses to changes in forest structure and composition. These effects can vary across spatial scales and be captured in hierarchical population models, which can serve to disentangle common trends from data when examining drivers of population dynamics like forest management or climate change.}, } @article {pmid30151152, year = {2018}, author = {Rajkov, J and Weber, AA and Salzburger, W and Egger, B}, title = {Adaptive phenotypic plasticity contributes to divergence between lake and river populations of an East African cichlid fish.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7323-7333}, pmid = {30151152}, issn = {2045-7758}, abstract = {Adaptive phenotypic plasticity and fixed genotypic differences have long been considered opposing strategies in adaptation. More recently, these mechanisms have been proposed to act complementarily and under certain conditions jointly facilitate evolution, speciation, and even adaptive radiations. Here, we investigate the relative contributions of adaptive phenotypic plasticity vs. local adaptation to fitness, using an emerging model system to study early phases of adaptive divergence, the generalist cichlid fish species Astatotilapia burtoni. We tested direct fitness consequences of morphological divergence between lake and river populations in nature by performing two transplant experiments in Lake Tanganyika. In the first experiment, we used wild-caught juvenile lake and river individuals, while in the second experiment, we used F1 crosses between lake and river fish bred in a common garden setup. By tracking the survival and growth of translocated individuals in enclosures in the lake over several weeks, we revealed local adaptation evidenced by faster growth of the wild-caught resident population in the first experiment. On the other hand, we did not find difference in growth between different types of F1 crosses in the second experiment, suggesting a substantial contribution of adaptive phenotypic plasticity to increased immigrant fitness. Our findings highlight the value of formally comparing fitness of wild-caught and common garden-reared individuals and emphasize the necessity of considering adaptive phenotypic plasticity in the study of adaptive divergence.}, } @article {pmid30151151, year = {2018}, author = {Ahrestani, FS and Kumar, NS and Vaidyanathan, S and Hiby, L and Jathanna, D and Karanth, KU}, title = {Estimating densities of large herbivores in tropical forests: Rigorous evaluation of a dung-based method.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7312-7322}, pmid = {30151151}, issn = {2045-7758}, abstract = {When sighting-based surveys to estimate population densities of large herbivores in tropical dense forests are not practical or affordable, surveys that rely on animal dung are sometimes used. This study tested one such dung-based method by deriving population densities from observed dung densities of six large herbivores (chital, elephant, gaur, muntjac, sambar, and wild pig) in two habitats, dry deciduous forests (DDF) and moist deciduous forests (MDF), within Nagarahole National Park, southern India. Using the program DUNGSURV, dung pile counts, decay rates estimated from field experiments, and defecation rates derived from literature were analyzed together by a model that allows for random events affecting dung decay. Densities of chital were the highest, followed by sambar. Wild pig densities were similar in the two habitats, sambar densities were higher in DDF, and densities of the other species were higher in MDF than in DDF. We compared DUNGSURV estimates with densities estimated using distance sampling in the same season. DUNGSURV estimates were substantially higher for all species in both habitats. These differences highlight the challenges that researchers face in computing unbiased estimates of dung decay rates and in relying on defecation rates from literature. Besides the elephant, this study is the first to rigorously test the efficacy of using a dung-based approach to estimate densities of large herbivore species in Asia, and based on this evaluation, we provide specific recommendations to address issues that require careful consideration before observed dung densities are used to derive animal densities. Our results underline the need for an experimental study of a known population in a fenced reserve to validate the true potential of using dung-based approaches to estimate population densities.}, } @article {pmid30151150, year = {2018}, author = {Šigut, M and Šigutová, H and Šipoš, J and Pyszko, P and Kotásková, N and Drozd, P}, title = {Vertical canopy gradient shaping the stratification of leaf-chewer-parasitoid interactions in a temperate forest.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7297-7311}, pmid = {30151150}, issn = {2045-7758}, abstract = {Knowledge about herbivores and their parasitoids in forest canopies remains limited, despite their diversity and ecological importance. Thus, it is important to understand the factors that shape the herbivore-parasitoid community structure, particularly the effect of vertical gradient. We investigated a quantitative community dataset of exposed and semiconcealed leaf-chewing larvae and their parasitoids along a vertical canopy gradient in a temperate forest. We sampled target insects using an elevated work platform in a 0.2 ha broadleaf deciduous forest plot in the Czech Republic. We analyzed the effect of vertical position among three canopy levels (first [lowest], second [middle], and third [highest]) and tree species on community descriptors (density, diversity, and parasitism rate) and food web structure. We also analyzed vertical patterns in density and parasitism rate between exposed and semiconcealed hosts, and the vertical preference of the most abundant parasitoid taxa in relation to their host specificity. Tree species was an important determinant of all community descriptors and food web structure. Insect density and diversity varied with the vertical gradient, but was only significant for hosts. Both host guilds were most abundant in the second level, but only the density of exposed hosts declined in the third level. Parasitism rate decreased from the first to third level. The overall parasitism rate did not differ between guilds, but semiconcealed hosts suffered lower parasitism in the third level. Less host-specific taxa (Ichneumonidae, Braconidae) operated more frequently lower in the canopy, whereas more host-specific Tachinidae followed their host distribution. The most host-specific Chalcidoidea preferred the third level. Vertical stratification of insect density, diversity, and parasitism rate was most pronounced in the tallest tree species. Therefore, our study contradicts the general paradigm of weak arthropod stratification in temperate forest canopies. However, in the network structure, vertical variation might be superseded by variation among tree species.}, } @article {pmid30151149, year = {2018}, author = {Wang, Y and Freckleton, RP and Wang, B and Kuang, X and Yuan, Z and Lin, F and Ye, J and Wang, X and Hao, Z}, title = {The role of breeding system in community dynamics: Growth and mortality in forests of different successional stages.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7285-7296}, pmid = {30151149}, issn = {2045-7758}, abstract = {Plant sexual systems appear to play an important role in community assembly: Dioecious species are found to tend to have a higher propensity to colonize communities in early successional stages. Here, we test two demographic hypotheses to explain this pattern in temperate forests. First, we test demographic differences between hermaphrodite and dioecious species in stressful younger successional stages: Previous theory predicts that hermaphrodite seed production is more harmed in stressful environments than that of dioecious populations leading to an advantage for females of dioecious species. Second, in primary forest, we hypothesized that dioecious species would show demographic advantage over monomorphic ones. We used data from two temperate forest plots in Northeast China surveyed over 10 years to compare the rates of growth and mortality of tree species with contrasting breeding systems in both secondary and primary forests. We assessed the effect of breeding system on the growth-mortality trade-off, while controlling for other traits usually considered as correlates of growth and mortality rates. We show that in the secondary forest, dioecious species showed weak advantage in demographic rates compared with monomorphic species; dioecious species showed considerably both lower relative growth and mortality rates compared to the hermaphrodites in the primary forest over 10 years, consistent with a priori predictions. Hermaphrodites showed strong growth-mortality trade-offs across forest stages, even when possibly confounding factors had been accounted for. These results suggest that sexual system influences community succession and assembly by acting on the rates of growth and mortality, and the trade-off between them. As vegetation develops, the demographic differences between breeding systems are much larger. Our results demonstrate the association between breeding system, succession, and community assembly and that this relationship is succession-stage dependent. Our findings support the suggestion that the demographic advantage of dioecious species facilitates the coexistence of sexual systems in primary forest.}, } @article {pmid30151148, year = {2018}, author = {Dieker, P and Beckmann, L and Teckentrup, J and Schielzeth, H}, title = {Spatial analyses of two color polymorphisms in an alpine grasshopper reveal a role of small-scale heterogeneity.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7273-7284}, pmid = {30151148}, issn = {2045-7758}, abstract = {Discrete color polymorphisms represent a fascinating aspect of intraspecific diversity. Color morph ratios often vary clinally, but in some cases, there are no marked clines and mixes of different morphs occur at appreciable frequencies in most populations. This poses the questions of how polymorphisms are maintained. We here study the spatial and temporal distribution of a very conspicuous color polymorphism in the club-legged grasshopper Gomphocerus sibiricus. The species occurs in a green and a nongreen (predominately brown) morph, a green-brown polymorphism that is common among Orthopteran insects. We sampled color morph ratios at 42 sites across the alpine range of the species and related color morph ratios to local habitat parameters and climatic conditions. Green morphs occurred in both sexes, and their morph ratios were highly correlated among sites, suggesting shared control of the polymorphism in females and males. We found that in at least 40 of 42 sites green and brown morphs co-occurred with proportions of green ranging from 0% to 70% with significant spatial heterogeneity. The proportion of green individuals tended to increase with decreasing summer and winter precipitations. Nongreen individuals can be further distinguished into brown and pied individuals, and again, this polymorphism is shared with other grasshopper species. We found pied individuals at all sites with proportions ranging from 3% to 75%, with slight, but significant variation between years. Pied morphs show a clinal increase in frequency from east to west and decreased with altitude and lower temperatures and were more common on grazed sites. The results suggest that both small-scale and large-scale spatial heterogeneity affects color morph ratios. The almost universal co-occurrence of all three color morphs argues against strong effects of genetic drift. Instead, the data suggest that small-scale migration-selection balance and/or local balancing selection maintain populations polymorphic.}, } @article {pmid30151147, year = {2018}, author = {Liu, H and Cai, S and Liu, J and Zhang, H}, title = {Comparative mitochondrial genomic analyses of three chemosynthetic vesicomyid clams from deep-sea habitats.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7261-7272}, pmid = {30151147}, issn = {2045-7758}, abstract = {Vesicomyid clams of the subfamily Pliocardinae are among the dominant chemosymbiotic bivalves found in sulfide-rich deep-sea habitats. Plastic morphologies and present molecular data could not resolve taxonomic uncertainties. The complete mitochondrial (mt) genomes will provide more data for comparative studies on molecular phylogeny and systematics of this taxonomically uncertain group, and help to clarify generic classifications. In this study, we analyze the features and evolutionary dynamics of mt genomes from three Archivesica species (Archivesica sp., Ar. gigas and Ar. pacifica) pertaining to subfamily Pliocardinae. Sequence coverage is nearly complete for the three newly sequenced mt genomes, with only the control region and some tRNA genes missing. Gene content, base composition, and codon usage are highly conserved in these pliocardiin species. Comparative analysis revealed the vesicomyid have a relatively lower ratio of Ka/Ks, and all 13 protein-coding genes (PGCs) are under strong purifying selection with a ratio of Ka/Ks far lower than one. Minimal changes in gene arrangement among vesicomyid species are due to the translocation trnaG in Isorropodon fossajaponicum. Additional tRNA genes were detected between trnaG and nad2 in Abyssogena mariana (trnaL3), Ab. phaseoliformis (trnaS3), and Phreagena okutanii (trnaM2), and display high similarity to other pliocardiin sequences at the same location. Single base insertion in multiple sites of this location could result in new tRNA genes, suggesting a possible tRNA arising from nongeneic sequence. Phylogenetic analysis based on 12 PCGs (excluding atp8) supports the monophyly of Pliocardiinae. These nearly complete mitogenomes provide relevant data for further comparative studies on molecular phylogeny and systematics of this taxonomically uncertain group of chemosymbiotic bivalves.}, } @article {pmid30151146, year = {2018}, author = {Wrubel, E and Parker, VT}, title = {Local patterns of diversity in California northern coastal scrub.}, journal = {Ecology and evolution}, volume = {8}, number = {15}, pages = {7250-7260}, pmid = {30151146}, issn = {2045-7758}, abstract = {Within global biodiversity hotspots such as the California Floristic Province, local patterns of diversity must be better understood to prioritize conservation for the greatest number of species. This study investigates patterns of vascular plant diversity in relation to coast-inland environmental gradients in the shrublands of Central California known as northern coastal scrub. We sampled coastal shrublands of the San Francisco Bay Area at coastal and inland locations, modeled fine-scale climatic variables, and developed an index for local exposure to maritime salts. We compared diversity, composition, and structure of the coastal and inland plots using indirect gradient analysis and estimated species accumulation using rarefaction curves. Coastal plots were significantly higher in alpha, beta, and gamma diversity than inland plots. Plant diversity (effective species number) in coastal plots was 2.1 times greater than inland plots, and beta diversity was 1.9 times greater. Estimated richness by rarefaction was 2.05 times greater in coastal sites than inland sites. Salt deposition and water availability were the abiotic process most strongly correlated with increased maritime plant diversity and compositional differences. Stands of northern coastal scrub on the immediate coast with higher maritime influence exhibit markedly higher plant diversity than most interior stands, paralleling previous work in other vegetation types in this region. These studies suggest that the California coastline deserves special consideration for botanical conservation. Fine-scale climatic models of cloud frequency, water availability, and the salt deposition index presented here can be used to define priority areas for plant conservation in California and other coastal regions worldwide.}, } @article {pmid30151053, year = {2018}, author = {Farinelli, D and Breton, C and Koubouris, G and Famiani, F and Villemur, P and Bervillé, A}, title = {Reply to Saumitou-Laprade et al. (2017) "Controlling for genetic identity of varieties, pollen contamination and stigma receptivity is essential to characterize the self-incompatibility system of Olea europaea L.". Eva:https://doi.org/10.1111/eva.12498.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1465-1470}, pmid = {30151053}, issn = {1752-4571}, abstract = {This study was carried out to examine the validity of previous studies on the intercompatibility of olive and to compare the approach and techniques used for proposing the diallelic self-incompatibility system and the sporophytic self-incompatibility system. Analysis of the literature indicates that the mating system of the olive tree is a controversial issue and requires further studies to clearly and fully comprehend it. All possible approaches should be used to maximize reliability of the final conclusions on the olive mating system.}, } @article {pmid30151052, year = {2018}, author = {Drinan, DP and Gruenthal, KM and Canino, MF and Lowry, D and Fisher, MC and Hauser, L}, title = {Population assignment and local adaptation along an isolation-by-distance gradient in Pacific cod (Gadus macrocephalus).}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1448-1464}, pmid = {30151052}, issn = {1752-4571}, abstract = {The discernment of populations as management units is a fundamental prerequisite for sustainable exploitation of species. A lack of clear stock boundaries complicates not only the identification of spatial management units, but also the assessment of mixed fisheries by population assignment and mixed stock analysis. Many marine species, such as Pacific cod, are characterized by isolation by distance, showing significant differentiation but no clear stock boundaries. Here, we used restriction-site-associated DNA (RAD) sequencing to investigate population structure and assess power to genetically assign Pacific cod to putative populations of origin. Samples were collected across the species range in the eastern Pacific Ocean, from the Salish Sea to the Aleutian Islands. A total of 6,425 putative biallelic single nucleotide polymorphisms were identified from 276 individuals. We found a strong isolation-by-distance signal along coastlines that mirrored previous microsatellite results and pronounced genetic differentiation between coastal samples and those from the inland waters of the Salish Sea, with no evidence for hybridization between these two populations. Individual assignment success based on two methods was high overall (≥84%) but decreased from south to north. Assignment to geographic location of origin also was successful, with average distance between capture and assignment location of 220 km. Outlier analyses identified more loci potentially under selection along the coast than between Salish Sea and coastal samples, suggesting more diverse adaptation to latitudinal environmental factors than inshore vs. offshore environments. Our results confirm previous observations of sharp genetic differentiation of the Salish Sea population and isolation by distance along the coast, but also highlight the feasibility of using modern genomic techniques to inform stock boundaries and fisheries management in a low FST marine species.}, } @article {pmid30151051, year = {2018}, author = {Dalongeville, A and Andrello, M and Mouillot, D and Lobreaux, S and Fortin, MJ and Lasram, F and Belmaker, J and Rocklin, D and Manel, S}, title = {Geographic isolation and larval dispersal shape seascape genetic patterns differently according to spatial scale.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1437-1447}, pmid = {30151051}, issn = {1752-4571}, abstract = {Genetic variation, as a basis of evolutionary change, allows species to adapt and persist in different climates and environments. Yet, a comprehensive assessment of the drivers of genetic variation at different spatial scales is still missing in marine ecosystems. Here, we investigated the influence of environment, geographic isolation, and larval dispersal on the variation in allele frequencies, using an extensive spatial sampling (47 locations) of the striped red mullet (Mullus surmuletus) in the Mediterranean Sea. Univariate multiple regressions were used to test the influence of environment (salinity and temperature), geographic isolation, and larval dispersal on single nucleotide polymorphism (SNP) allele frequencies. We used Moran's eigenvector maps (db-MEMs) and asymmetric eigenvector maps (AEMs) to decompose geographic and dispersal distances in predictors representing different spatial scales. We found that salinity and temperature had only a weak effect on the variation in allele frequencies. Our results revealed the predominance of geographic isolation to explain variation in allele frequencies at large spatial scale (>1,000 km), while larval dispersal was the major predictor at smaller spatial scale (<1,000 km). Our findings stress the importance of including spatial scales to understand the drivers of spatial genetic variation. We suggest that larval dispersal allows to maintain gene flows at small to intermediate scale, while at broad scale, genetic variation may be mostly shaped by adult mobility, demographic history, or multigenerational stepping-stone dispersal. These findings bring out important spatial scale considerations to account for in the design of a protected area network that would efficiently enhance protection and persistence capacity of marine species.}, } @article {pmid30151050, year = {2018}, author = {Zhang, C and Jansen, M and De Meester, L and Stoks, R}, title = {Thermal evolution offsets the elevated toxicity of a contaminant under warming: A resurrection study in Daphnia magna.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1425-1436}, pmid = {30151050}, issn = {1752-4571}, abstract = {Synergistic interactions between temperature and contaminants are a major challenge for ecological risk assessment, especially under global warming. While thermal evolution may increase the ability to deal with warming, it is unknown whether it may also affect the ability to deal with the many contaminants that are more toxic at higher temperatures. We investigated how evolution of genetic adaptation to warming affected the interactions between warming and a novel stressor: zinc oxide nanoparticles (nZnO) in a natural population of Daphnia magna using resurrection ecology. We hatched resting eggs from two D. magna subpopulations (old: 1955-1965, recent: 1995-2005) from the sediment of a lake that experienced an increase in average temperature and in recurrence of heat waves but was never exposed to industrial waste. In the old "ancestral" subpopulation, exposure to a sublethal concentration of nZnO decreased the intrinsic growth rate, metabolic activity, and energy reserves at 24°C but not at 20°C, indicating a synergism between warming and nZnO. In contrast, these synergistic effects disappeared in the recent "derived" subpopulation that evolved a lower sensitivity to nZnO at 24°C, which indicates that thermal evolution could offset the elevated toxicity of nZnO under warming. This evolution of reduced sensitivity to nZnO under warming could not be explained by changes in the total internal zinc accumulation but was partially associated with the evolution of the expression of a key metal detoxification gene under warming. Our results suggest that the increased sensitivity to the sublethal concentration of nZnO under the predicted 4°C warming by the end of this century may be counteracted by thermal evolution in this D. magna population. Our results illustrate the importance of evolution to warming in shaping the responses to another anthropogenic stressor, here a contaminant. More general, genetic adaptation to an environmental stressor may ensure that synergistic effects between contaminants and this environmental stressor will not be present anymore.}, } @article {pmid30151049, year = {2018}, author = {Morbey, YE and Mema, M}, title = {Size-selective fishing and the potential for fisheries-induced evolution in lake whitefish.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1412-1424}, pmid = {30151049}, issn = {1752-4571}, abstract = {The long-term evolutionary effects of fishing on maturation schedules can depend on gear type, the shape of the gear type's size-selectivity function, and the size and age structure of a population. Our goal was to better understand how environmentally induced differences in somatic growth influence the evolutionary effects of size-selective fisheries, using lake whitefish (Coregonus clupeaformis) in Lake Huron as a case study. Using a state-dependent optimization model of energy allocation parameterized for lake whitefish, we show that fishing with gill nets (bell-shaped selectivity) and trap nets (sigmoid-shaped selectivity) can be potent agents of selection on size thresholds for maturity. Compared to trap nets and large mesh (114 mm) gill nets, small mesh (89 mm) gill nets are better able to buffer populations from fishing-induced evolution by safeguarding large, fecund fish, but only when overall fishing mortality is low and growth rates sufficiently fast such that fish can outgrow vulnerable size classes. Regardless of gear type, and all else being equal, high fishing mortality in combination with low growth rates is expected to intensify the long-term evolutionary effects of fishing.}, } @article {pmid30151048, year = {2018}, author = {Trejo, L and Rosell, JA and Olson, ME}, title = {Nearly 200 years of sustained selection have not overcome the leaf area-stem size relationship in the poinsettia.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1401-1411}, pmid = {30151048}, issn = {1752-4571}, abstract = {Organismal parts often covary in their proportions, a phenomenon known as allometry. One way of exploring the causes of widespread allometric patterns is with artificial selection, to test whether or not it is possible to move populations into "empty" allometric space not occupied by the wild type. Domesticated organisms have been subject to many generations of selection, making them ideal model systems. We used the domesticated Christmas poinsettia Euphorbia pulcherrima in combination with wild populations to examine the origin of the proportionality between leaf area and stem size, which scales predictably across nearly all plants. In accordance with the stated aims of breeders to produce more compact plants, we predicted that domesticated poinsettias would have greater leaf area for a given stem volume than the tall, lanky wild ancestors. Our data rejected this prediction, showing instead that domesticates have leaf area-stem volume relationships identical to the wild ancestors. Presumably the metabolic dependence between stems and leaves makes the leaf area-stem volume relationship difficult to overcome. The relative fixity of this relationship leads to predictable covariation in other traits: The fuller outlines of domestic poinsettias involve significantly shorter internodes, and given a constant leaf area-stem volume relationship, smaller individual leaf areas. At the same time, domestic poinsettias are subject to selection favoring breakage resistance, which is achieved via thicker stems for a given length rather than stiffer stem tissue resistance to bending. Our results show that domesticated poinsettias differ from wild plants in a suite of traits including leaf size, internode distances, and stem length-diameter relations, but despite over 200 years of selection favoring rounded outlines, there has been no change in the total leaf area-stem volume relationship, helping to predict which changes are likely achievable and which will not be under continued artificial selection and in the wild.}, } @article {pmid30151047, year = {2018}, author = {Marshall, DJ and Lawton, RJ and Monro, K and Paul, NA}, title = {Biochemical evolution in response to intensive harvesting in algae: Evolution of quality and quantity.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1389-1400}, pmid = {30151047}, issn = {1752-4571}, abstract = {Evolutionary responses to indirect selection pressures imposed by intensive harvesting are increasingly common. While artificial selection has shown that biochemical components can show rapid and dramatic evolution, it remains unclear as to whether intensive harvesting can inadvertently induce changes in the biochemistry of harvested populations. For applications such as algal culture, many of the desirable bioproducts could evolve in response to harvesting, reducing cost-effectiveness, but experimental tests are lacking. We used an experimental evolution approach where we imposed heavy and light harvesting regimes on multiple lines of an alga of commercial interest for twelve cycles of harvesting and then placed all lines in a common garden regime for four cycles. We have previously shown that lines in a heavy harvesting regime evolve a "live fast" phenotype with higher growth rates relative to light harvesting regimes. Here, we show that algal biochemistry also shows evolutionary responses, although they were temporarily masked by differences in density under the different harvesting regimes. Heavy harvesting regimes, relative to light harvesting regimes, had reduced productivity of desirable bioproducts, particularly fatty acids. We suggest that commercial operators wishing to maximize productivity of desirable bioproducts should maintain mother cultures, kept at higher densities (which tend to select for desirable phenotypes), and periodically restart their intensively harvested cultures to minimize the negative consequences of biochemical evolution. Our study shows that the burgeoning algal culture industry should pay careful attention to the role of evolution in intensively harvested crops as these effects are nontrivial if subtle.}, } @article {pmid30151046, year = {2018}, author = {Cook, CN and Sgrò, CM}, title = {Understanding managers' and scientists' perspectives on opportunities to achieve more evolutionarily enlightened management in conservation.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1371-1388}, pmid = {30151046}, issn = {1752-4571}, abstract = {Despite wide acceptance that conservation could benefit from greater attention to principles and processes from evolutionary biology, little attention has been given to quantifying the degree to which relevant evolutionary concepts are being integrated into management practices. There has also been increasing discussion of the potential reasons for a lack of evolutionarily enlightened management, but no attempts to understand the challenges from the perspective of those making management decisions. In this study, we asked conservation managers and scientists for their views on the importance of a range of key evolutionary concepts, the degree to which these concepts are being integrated into management, and what would need to change to support better integration into management practices. We found that while managers recognize the importance of a wide range of evolutionary concepts for conservation outcomes, they acknowledge these concepts are rarely incorporated into management. Managers and scientists were in strong agreement about the range of barriers that need to be overcome, with a lack of knowledge reported as the most important barrier to better integration of evolutionary biology into conservation decision-making. Although managers tended to be more focused on the need for more training in evolutionary biology, scientists reported greater engagement between managers and evolutionary biologists as most important to achieve the necessary change. Nevertheless, the challenges appear to be multifaceted, and several are outside the control of managers, suggesting solutions will need to be multidimensional.}, } @article {pmid30151045, year = {2018}, author = {Bousset, L and Sprague, SJ and Thrall, PH and Barrett, LG}, title = {Spatio-temporal connectivity and host resistance influence evolutionary and epidemiological dynamics of the canola pathogen Leptosphaeria maculans.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1354-1370}, pmid = {30151045}, issn = {1752-4571}, abstract = {Genetic, physiological and physical homogenization of agricultural landscapes creates ideal environments for plant pathogens to proliferate and rapidly evolve. Thus, a critical challenge in plant pathology and epidemiology is to design durable and effective strategies to protect cropping systems from damage caused by pathogens. Theoretical studies suggest that spatio-temporal variation in the diversity and distribution of resistant hosts across agricultural landscapes may have strong effects on the epidemiology and evolutionary potential of crop pathogens. However, we lack empirical tests of spatio-temporal deployment of host resistance to pathogens can be best used to manage disease epidemics and disrupt pathogen evolutionary dynamics in real-world systems. In a field experiment, we simulated how differences in Brassica napus resistance deployment strategies and landscape connectivity influence epidemic severity and Leptosphaeria maculans pathogen population composition. Host plant resistance, spatio-temporal connectivity [stubble loads], and genetic connectivity of the inoculum source [composition of canola stubble mixtures] jointly impacted epidemiology (disease severity) and pathogen evolution (population composition). Changes in population composition were consistent with directional selection for the ability to infect the host (infectivity), leading to changes in pathotype (multilocus phenotypes) and infectivity frequencies. We repeatedly observed decreases in the frequency of unnecessary infectivity, suggesting that carrying multiple infectivity genes is costly for the pathogen. From an applied perspective, our results indicate that varying resistance genes in space and time can be used to help control disease, even when resistance has already been overcome. Furthermore, our approach extends our ability to test not only for the efficacy of host varieties in a given year, but also for durability over multiple cropping seasons, given variation in the combination of resistance genes deployed.}, } @article {pmid30151044, year = {2018}, author = {Yang, L and Ouyang, HB and Fang, ZG and Zhu, W and Wu, EJ and Luo, GH and Shang, LP and Zhan, J}, title = {Evidence for intragenic recombination and selective sweep in an effector gene of Phytophthora infestans.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1342-1353}, pmid = {30151044}, issn = {1752-4571}, abstract = {Effectors, a group of small proteins secreted by pathogens, play a critical role in the antagonistic interaction between plant hosts and pathogens through their dual functions in regulating host immune systems and pathogen infection capability. In this study, evolution in effector genes was investigated through population genetic analysis of Avr3a sequences generated from 96 Phytophthora infestans isolates collected from six locations representing a range of thermal variation and cropping systems in China. We found high genetic variation in the Avr3a gene resulting from diverse mechanisms extending beyond point mutations, frameshift, and defeated start and stop codons to intragenic recombination. A total of 51 nucleotide haplotypes encoding 38 amino acid isoforms were detected in the 96 full sequences with nucleotide diversity in the pathogen populations ranging from 0.007 to 0.023 (mean = 0.017). Although haplotype and nucleotide diversity were high, the effector gene was dominated by only three haplotypes. Evidence for a selective sweep was provided by (i) the population genetic differentiation (GST) of haplotypes being lower than the population differentiation (FST) of SSR marker loci; and (ii) negative values of Tajima's D and Fu's FS. Annual mean temperature in the collection sites was negatively correlated with the frequency of the virulent form (Avr3aEM), indicating Avr3a may be regulated by temperature. These results suggest that elevated air temperature due to global warming may hamper the development of pathogenicity traits in P. infestans and further study under confined thermal regimes may be required to confirm the hypothesis.}, } @article {pmid30151043, year = {2018}, author = {do Prado, FD and Vera, M and Hermida, M and Bouza, C and Pardo, BG and Vilas, R and Blanco, A and Fernández, C and Maroso, F and Maes, GE and Turan, C and Volckaert, FAM and Taggart, JB and Carr, A and Ogden, R and Nielsen, EE and , and Martínez, P}, title = {Parallel evolution and adaptation to environmental factors in a marine flatfish: Implications for fisheries and aquaculture management of the turbot (Scophthalmus maximus).}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1322-1341}, pmid = {30151043}, issn = {1752-4571}, abstract = {Unraveling adaptive genetic variation represents, in addition to the estimate of population demographic parameters, a cornerstone for the management of aquatic natural living resources, which, in turn, represent the raw material for breeding programs. The turbot (Scophthalmus maximus) is a marine flatfish of high commercial value living on the European continental shelf. While wild populations are declining, aquaculture is flourishing in southern Europe. We evaluated the genetic structure of turbot throughout its natural distribution range (672 individuals; 20 populations) by analyzing allele frequency data from 755 single nucleotide polymorphism discovered and genotyped by double-digest RAD sequencing. The species was structured into four main regions: Baltic Sea, Atlantic Ocean, Adriatic Sea, and Black Sea, with subtle differentiation apparent at the distribution margins of the Atlantic region. Genetic diversity and effective population size estimates were highest in the Atlantic populations, the area of greatest occurrence, while turbot from other regions showed lower levels, reflecting geographical isolation and reduced abundance. Divergent selection was detected within and between the Atlantic Ocean and Baltic Sea regions, and also when comparing these two regions with the Black Sea. Evidence of parallel evolution was detected between the two low salinity regions, the Baltic and Black seas. Correlation between genetic and environmental variation indicated that temperature and salinity were probably the main environmental drivers of selection. Mining around the four genomic regions consistently inferred to be under selection identified candidate genes related to osmoregulation, growth, and resistance to diseases. The new insights are useful for the management of turbot fisheries and aquaculture by providing the baseline for evaluating the consequences of turbot releases from restocking and farming.}, } @article {pmid30151042, year = {2018}, author = {Row, JR and Doherty, KE and Cross, TB and Schwartz, MK and Oyler-McCance, SJ and Naugle, DE and Knick, ST and Fedy, BC}, title = {Quantifying functional connectivity: The role of breeding habitat, abundance, and landscape features on range-wide gene flow in sage-grouse.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1305-1321}, pmid = {30151042}, issn = {1752-4571}, abstract = {Functional connectivity, quantified using landscape genetics, can inform conservation through the identification of factors linking genetic structure to landscape mechanisms. We used breeding habitat metrics, landscape attributes, and indices of grouse abundance, to compare fit between structural connectivity and genetic differentiation within five long-established Sage-Grouse Management Zones (MZ) I-V using microsatellite genotypes from 6,844 greater sage-grouse (Centrocercus urophasianus) collected across their 10.7 million-km2 range. We estimated structural connectivity using a circuit theory-based approach where we built resistance surfaces using thresholds dividing the landscape into "habitat" and "nonhabitat" and nodes were clusters of sage-grouse leks (where feather samples were collected using noninvasive techniques). As hypothesized, MZ-specific habitat metrics were the best predictors of differentiation. To our surprise, inclusion of grouse abundance-corrected indices did not greatly improve model fit in most MZs. Functional connectivity of breeding habitat was reduced when probability of lek occurrence dropped below 0.25 (MZs I, IV) and 0.5 (II), thresholds lower than those previously identified as required for the formation of breeding leks, which suggests that individuals are willing to travel through undesirable habitat. The individual MZ landscape results suggested terrain roughness and steepness shaped functional connectivity across all MZs. Across respective MZs, sagebrush availability (<10%-30%; II, IV, V), tree canopy cover (>10%; I, II, IV), and cultivation (>25%; I, II, IV, V) each reduced movement beyond their respective thresholds. Model validations confirmed variation in predictive ability across MZs with top resistance surfaces better predicting gene flow than geographic distance alone, especially in cases of low and high differentiation among lek groups. The resultant resistance maps we produced spatially depict the strength and redundancy of range-wide gene flow and can help direct conservation actions to maintain and restore functional connectivity for sage-grouse.}, } @article {pmid30151041, year = {2018}, author = {Egan, PA and Muola, A and Stenberg, JA}, title = {Capturing genetic variation in crop wild relatives: An evolutionary approach.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1293-1304}, pmid = {30151041}, issn = {1752-4571}, abstract = {Crop wild relatives (CWRs) offer novel genetic resources for crop improvement. To assist in the urgent need to collect and conserve CWR germplasm, we advance here the concept of an "evolutionary" approach. Central to this approach is the predictive use of spatial proxies of evolutionary processes (natural selection, gene flow and genetic drift) to locate and capture genetic variation. As a means to help validate this concept, we screened wild-collected genotypes of woodland strawberry (Fragaria vesca) in a common garden. A quantitative genetic approach was then used to test the ability of two such proxies-mesoclimatic variation (a proxy of natural selection) and landscape isolation and geographic distance between populations (proxies of gene flow potential)-to predict spatial genetic variation in three quantitative traits (plant size, early season flower number and flower frost tolerance). Our results indicated a significant but variable effect of mesoclimatic conditions in structuring genetic variation in the wild, in addition to other undetermined regional scale processes. As a proxy of gene flow potential, landscape isolation was also a likely determinant of observed patterns-as opposed to, and regardless of, geographic distance between populations. We conclude that harnessing proxies of adaptive and nonadaptive evolutionary processes could provide a robust and valuable means to identify genetic variation in CWRs. We thus advocate wider use and development of this approach amongst researchers, breeders and practitioners, to expedite the capture and in situ conservation of genetic resources provided by crop wild relatives.}, } @article {pmid30151040, year = {2018}, author = {Aguadé-Gorgorió, G and Solé, R}, title = {Adaptive dynamics of unstable cancer populations: The canonical equation.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1283-1292}, pmid = {30151040}, issn = {1752-4571}, abstract = {In most instances of tumour development, genetic instability plays a role in allowing cancer cell populations to respond to selection barriers, such as physical constraints or immune responses, and rapidly adapt to an always changing environment. Modelling instability is a nontrivial task, since by definition evolving instability leads to changes in the underlying landscape. In this article, we explore mathematically a simple version of unstable tumour progression using the formalism of adaptive dynamics (AD) where selection and mutation are explicitly coupled. Using a set of basic fitness landscapes, the so-called canonical equation for the evolution of genetic instability on a minimal scenario associated with a population of unstable cells is derived. We obtain explicit expressions for the evolution of mutation probabilities, and the implications of the model on further experimental studies and potential mutagenic therapies are discussed.}, } @article {pmid30151039, year = {2018}, author = {Henriques, D and Parejo, M and Vignal, A and Wragg, D and Wallberg, A and Webster, MT and Pinto, MA}, title = {Developing reduced SNP assays from whole-genome sequence data to estimate introgression in an organism with complex genetic patterns, the Iberian honeybee (Apis mellifera iberiensis).}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1270-1282}, pmid = {30151039}, issn = {1752-4571}, abstract = {The most important managed pollinator, the honeybee (Apis mellifera L.), has been subject to a growing number of threats. In western Europe, one such threat is large-scale introductions of commercial strains (C-lineage ancestry), which is leading to introgressive hybridization and even the local extinction of native honeybee populations (M-lineage ancestry). Here, we developed reduced assays of highly informative SNPs from 176 whole genomes to estimate C-lineage introgression in the most diverse and evolutionarily complex subspecies in Europe, the Iberian honeybee (Apis mellifera iberiensis). We started by evaluating the effects of sample size and sampling a geographically restricted area on the number of highly informative SNPs. We demonstrated that a bias in the number of fixed SNPs (FST = 1) is introduced when the sample size is small (N ≤ 10) and when sampling only captures a small fraction of a population's genetic diversity. These results underscore the importance of having a representative sample when developing reliable reduced SNP assays for organisms with complex genetic patterns. We used a training data set to design four independent SNP assays selected from pairwise FST between the Iberian and C-lineage honeybees. The designed assays, which were validated in holdout and simulated hybrid data sets, proved to be highly accurate and can be readily used for monitoring populations not only in the native range of A. m. iberiensis in Iberia but also in the introduced range in the Balearic islands, Macaronesia and South America, in a time- and cost-effective manner. While our approach used the Iberian honeybee as model system, it has a high value in a wide range of scenarios for the monitoring and conservation of potentially hybridized domestic and wildlife populations.}, } @article {pmid30151038, year = {2018}, author = {Dusitsittipon, S and Criscione, CD and Morand, S and Komalamisra, C and Thaenkham, U}, title = {Hurdles in the evolutionary epidemiology of Angiostrongylus cantonensis: Pseudogenes, incongruence between taxonomy and DNA sequence variants, and cryptic lineages.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1257-1269}, pmid = {30151038}, issn = {1752-4571}, abstract = {Angiostrongylus cantonensis, the rat lungworm, is a zoonotic pathogen that is one of the leading causes of eosinophilic meningitis worldwide. This parasite is regarded as an emerging pathogen with a global range expansion out of southeastern Asia post-WWII. To date, molecular systematic/phylogeographic studies on A. cantonensis have mainly used two mitochondrial (mtDNA) markers, cytochrome c oxidase 1 (CO1) and cytochrome b (CYTB), where the focus has largely been descriptive in terms of reporting local patterns of haplotype variants. In order to look for more global evolutionary patterns, we herein provide a collective phylogenetic assessment using the six available whole mtDNA genome samples that have been tagged as A. cantonensis, A. malaysiensis, or A. mackerrasae along with all other GenBank CO1 and CYTB partial sequences that carry these species identifiers. The results reveal three important complications that researchers will need to be aware of, or will need to resolve, prior to conducting future molecular evolutionary studies on A. cantonensis. These three problems are (i) incongruence between taxonomic identifications and mtDNA variants (haplotypes or whole mtDNA genome samples), (ii) the presence of a CYTB mtDNA pseudogene, and (iii) the need to verify A. mackerrasae as a species along with other possible cryptic lineages, of which there is suggestive evidence (i.e., A. cantonensis could be a species complex). We provided a discussion of how these complications are hurdles to our understanding of the global epidemiology of angiostrongyliasis. We call for future studies to be more explicit in morphological traits used for identifications (e.g., provide measurements). Moreover, it will be necessary to repeat prior morphological and life-history studies while simultaneously using sequence data in order to assess possible associations between critical epidemiological data (e.g., biogeography, virulence/pathology, host species use) and specific lineages.}, } @article {pmid30151037, year = {2018}, author = {Assogba, BS and Alout, H and Koffi, A and Penetier, C and Djogbénou, LS and Makoundou, P and Weill, M and Labbé, P}, title = {Adaptive deletion in resistance gene duplications in the malaria vector Anopheles gambiae.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1245-1256}, pmid = {30151037}, issn = {1752-4571}, abstract = {While gene copy-number variations play major roles in long-term evolution, their early dynamics remains largely unknown. However, examples of their role in short-term adaptation are accumulating: identical repetitions of a locus (homogeneous duplications) can provide a quantitative advantage, while the association of differing alleles (heterogeneous duplications) allows carrying two functions simultaneously. Such duplications often result from rearrangements of sometimes relatively large chromosome fragments, and even when adaptive, they can be associated with deleterious side effects that should, however, be reduced by subsequent evolution. Here, we took advantage of the unique model provided by the malaria mosquito Anopheles gambiae s.l. to investigate the early evolution of several duplications, heterogeneous and homogeneous, segregating in natural populations from West Africa. These duplications encompass ~200 kb and 11 genes, including the adaptive insecticide resistance ace-1 locus. Through the survey of several populations from three countries over 3-4 years, we showed that an internal deletion of all coamplified genes except ace-1 is currently spreading in West Africa and introgressing from An. gambiae s.s. to An. coluzzii. Both observations provide evidences of its selection, most likely due to reducing the gene-dosage disturbances caused by the excessive copies of the nonadaptive genes. Our study thus provides a unique example of the early adaptive trajectory of duplications and underlines the role of the environmental conditions (insecticide treatment practices and species ecology). It also emphasizes the striking diversity of adaptive responses in these mosquitoes and reveals a worrisome process of resistance/cost trade-off evolution that could impact the control of malaria vectors in Africa.}, } @article {pmid30151036, year = {2018}, author = {Kingsolver, JG and Buckley, LB}, title = {How do phenology, plasticity, and evolution determine the fitness consequences of climate change for montane butterflies?.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1231-1244}, pmid = {30151036}, issn = {1752-4571}, abstract = {Species have responded to climate change via seasonal (phenological) shifts, morphological plasticity, and evolutionary adaptation, but how these responses contribute to changes and variation in population fitness are poorly understood. We assess the interactions and relative importance of these responses for fitness in a montane butterfly, Colias eriphyle, along an elevational gradient. Because environmental temperatures affect developmental rates of each life stage, populations along the gradients differ in phenological timing and the number of generations each year. Our focal phenotype, wing solar absorptivity of adult butterflies, exhibits local adaptation across elevation and responds plastically to developmental temperatures. We integrate climatic data for the past half-century with microclimate, developmental, biophysical, demographic, and evolutionary models for this system to predict how phenology, plasticity, and evolution contribute to phenotypic and fitness variation along the gradient. We predict that phenological advancements incompletely compensate for climate warming, and also influence morphological plasticity. Climate change is predicted to increase mean population fitness in the first seasonal generation at high elevation, but decrease mean fitness in the summer generations at low elevation. Phenological shifts reduce the interannual variation in directional selection and morphology, but do not have consistent effects on variation in mean fitness. Morphological plasticity and its evolution can substantially increase population fitness and adaptation to climate change at low elevations, but environmental unpredictability limits adaptive plastic and evolutionary responses at high elevations. Phenological shifts also decrease the relative fitness advantages of morphological plasticity and evolution. Our results illustrate how the potential contributions of phenological and morphological plasticity and of evolution to climate change adaptation can vary along environmental gradients and how environmental variability will limit adaptive responses to climate change in montane regions.}, } @article {pmid30151035, year = {2018}, author = {Draheim, HM and Moore, JA and Fortin, MJ and Scribner, KT}, title = {Beyond the snapshot: Landscape genetic analysis of time series data reveal responses of American black bears to landscape change.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1219-1230}, pmid = {30151035}, issn = {1752-4571}, abstract = {Landscape genetic studies typically focus on the evolutionary processes that give rise to spatial patterns that are quantified at a single point in time. Although landscape change is widely recognized as a strong driver of microevolutionary processes, few landscape genetic studies have directly evaluated the change in spatial genetic structure (SGS) over time with concurrent changes in landscape pattern. We introduce a novel approach to analyze landscape genetic data through time. We demonstrate this approach using genotyped samples (n = 569) from a large black bear (Ursus americanus) population in Michigan (USA) that were harvested during 3 years (2002, 2006, and 2010). We identified areas that were consistently occupied over this 9-year period and quantified temporal variation in SGS. Then, we evaluated alternative hypotheses about effects of changes in landscape features (e.g., deforestation or crop conversion) on fine-scale SGS among years using spatial autoregressive modeling and model selection. Relative measures of landscape change such as magnitude of landscape change (i.e., number of patches changing from suitable to unsuitable states or vice versa), and during later periods, measures of fragmentation (i.e., patch aggregation and cohesion) were associated with change in SGS. Our results stress the importance of conducting time series studies for the conservation and management of wildlife inhabiting rapidly changing landscapes.}, } @article {pmid30151034, year = {2018}, author = {Allendorf, FW}, title = {Zen and deep evolution: The optical delusion of separation.}, journal = {Evolutionary applications}, volume = {11}, number = {8}, pages = {1212-1218}, pmid = {30151034}, issn = {1752-4571}, abstract = {The Buddha taught that everything is connected and constantly changing. These fundamental observations of the world are shared by ecology and evolution. We are living in a time of unprecedented rates of extinction. Science provides us with the information that we need to address this extinction crisis. However, the problems underlying extinction generally do not result from a lack of scientific understanding, but they rather result from an unwillingness to take the needed action. I present mindfulness and meditative aspects of Zen practice that provide the deeper "knowing," or awareness that we need to inspire action on these problems.}, } @article {pmid30150775, year = {2018}, author = {Munschauer, M and Nguyen, CT and Sirokman, K and Hartigan, CR and Hogstrom, L and Engreitz, JM and Ulirsch, JC and Fulco, CP and Subramanian, V and Chen, J and Schenone, M and Guttman, M and Carr, SA and Lander, ES}, title = {The NORAD lncRNA assembles a topoisomerase complex critical for genome stability.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {132-136}, doi = {10.1038/s41586-018-0453-z}, pmid = {30150775}, issn = {1476-4687}, support = {DP5 OD012190/OD/NIH HHS/United States ; U01 DA040612/DA/NIDA NIH HHS/United States ; U01 HL130007/HL/NHLBI NIH HHS/United States ; }, abstract = {The human genome contains thousands of long non-coding RNAs1, but specific biological functions and biochemical mechanisms have been discovered for only about a dozen2-7. A specific long non-coding RNA-non-coding RNA activated by DNA damage (NORAD)-has recently been shown to be required for maintaining genomic stability8, but its molecular mechanism is unknown. Here we combine RNA antisense purification and quantitative mass spectrometry to identify proteins that directly interact with NORAD in living cells. We show that NORAD interacts with proteins involved in DNA replication and repair in steady-state cells and localizes to the nucleus upon stimulation with replication stress or DNA damage. In particular, NORAD interacts with RBMX, a component of the DNA-damage response, and contains the strongest RBMX-binding site in the transcriptome. We demonstrate that NORAD controls the ability of RBMX to assemble a ribonucleoprotein complex-which we term NORAD-activated ribonucleoprotein complex 1 (NARC1)-that contains the known suppressors of genomic instability topoisomerase I (TOP1), ALYREF and the PRPF19-CDC5L complex. Cells depleted for NORAD or RBMX display an increased frequency of chromosome segregation defects, reduced replication-fork velocity and altered cell-cycle progression-which represent phenotypes that are mechanistically linked to TOP1 and PRPF19-CDC5L function. Expression of NORAD in trans can rescue defects caused by NORAD depletion, but rescue is significantly impaired when the RBMX-binding site in NORAD is deleted. Our results demonstrate that the interaction between NORAD and RBMX is important for NORAD function, and that NORAD is required for the assembly of the previously unknown topoisomerase complex NARC1, which contributes to maintaining genomic stability. In addition, we uncover a previously unknown function for long non-coding RNAs in modulating the ability of an RNA-binding protein to assemble a higher-order ribonucleoprotein complex.}, } @article {pmid30150774, year = {2018}, author = {Bayer, EA and Hobert, O}, title = {Past experience shapes sexually dimorphic neuronal wiring through monoaminergic signalling.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {117-121}, pmid = {30150774}, issn = {1476-4687}, support = {F31 NS096863/NS/NINDS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R01 NS039996/NS/NINDS NIH HHS/United States ; R37 NS039996/NS/NINDS NIH HHS/United States ; }, abstract = {Differences between female and male brains exist across the animal kingdom and extend from molecular to anatomical features. Here we show that sexually dimorphic anatomy, gene expression and function in the nervous system can be modulated by past experiences. In the nematode Caenorhabditis elegans, sexual differentiation entails the sex-specific pruning of synaptic connections between neurons that are shared by both sexes, giving rise to sexually dimorphic circuits in adult animals1. We discovered that starvation during juvenile stages is memorized in males to suppress the emergence of sexually dimorphic synaptic connectivity. These circuit changes result in increased chemosensory responsiveness in adult males following juvenile starvation. We find that an octopamine-mediated starvation signal dampens the production of serotonin (5-HT) to convey the memory of starvation. Serotonin production is monitored by a 5-HT1A serotonin receptor homologue that acts cell-autonomously to promote the pruning of sexually dimorphic synaptic connectivity under well-fed conditions. Our studies demonstrate how life history shapes neurotransmitter production, synaptic connectivity and behavioural output in a sexually dimorphic circuit.}, } @article {pmid30150773, year = {2018}, author = {Lee, SH and Singh, I and Tisdale, S and Abdel-Wahab, O and Leslie, CS and Mayr, C}, title = {Widespread intronic polyadenylation inactivates tumour suppressor genes in leukaemia.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {127-131}, doi = {10.1038/s41586-018-0465-8}, pmid = {30150773}, issn = {1476-4687}, support = {U01 CA164190/CA/NCI NIH HHS/United States ; DP1 GM123454/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {DNA mutations are known cancer drivers. Here we investigated whether mRNA events that are upregulated in cancer can functionally mimic the outcome of genetic alterations. RNA sequencing or 3'-end sequencing techniques were applied to normal and malignant B cells from 59 patients with chronic lymphocytic leukaemia (CLL)1-3. We discovered widespread upregulation of truncated mRNAs and proteins in primary CLL cells that were not generated by genetic alterations but instead occurred by intronic polyadenylation. Truncated mRNAs caused by intronic polyadenylation were recurrent (n = 330) and predominantly affected genes with tumour-suppressive functions. The truncated proteins generated by intronic polyadenylation often lack the tumour-suppressive functions of the corresponding full-length proteins (such as DICER and FOXN3), and several even acted in an oncogenic manner (such as CARD11, MGA and CHST11). In CLL, the inactivation of tumour-suppressor genes by aberrant mRNA processing is substantially more prevalent than the functional loss of such genes through genetic events. We further identified new candidate tumour-suppressor genes that are inactivated by intronic polyadenylation in leukaemia and by truncating DNA mutations in solid tumours4,5. These genes are understudied in cancer, as their overall mutation rates are lower than those of well-known tumour-suppressor genes. Our findings show the need to go beyond genomic analyses in cancer diagnostics, as mRNA events that are silent at the DNA level are widespread contributors to cancer pathogenesis through the inactivation of tumour-suppressor genes.}, } @article {pmid30150772, year = {2018}, author = {Chen, Q and Wu, J and Ou, X and Huang, B and Almutlaq, J and Zhumekenov, AA and Guan, X and Han, S and Liang, L and Yi, Z and Li, J and Xie, X and Wang, Y and Li, Y and Fan, D and Teh, DBL and All, AH and Mohammed, OF and Bakr, OM and Wu, T and Bettinelli, M and Yang, H and Huang, W and Liu, X}, title = {All-inorganic perovskite nanocrystal scintillators.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {88-93}, doi = {10.1038/s41586-018-0451-1}, pmid = {30150772}, issn = {1476-4687}, abstract = {The rising demand for radiation detection materials in many applications has led to extensive research on scintillators1-3. The ability of a scintillator to absorb high-energy (kiloelectronvolt-scale) X-ray photons and convert the absorbed energy into low-energy visible photons is critical for applications in radiation exposure monitoring, security inspection, X-ray astronomy and medical radiography4,5. However, conventional scintillators are generally synthesized by crystallization at a high temperature and their radioluminescence is difficult to tune across the visible spectrum. Here we describe experimental investigations of a series of all-inorganic perovskite nanocrystals comprising caesium and lead atoms and their response to X-ray irradiation. These nanocrystal scintillators exhibit strong X-ray absorption and intense radioluminescence at visible wavelengths. Unlike bulk inorganic scintillators, these perovskite nanomaterials are solution-processable at a relatively low temperature and can generate X-ray-induced emissions that are easily tunable across the visible spectrum by tailoring the anionic component of colloidal precursors during their synthesis. These features allow the fabrication of flexible and highly sensitive X-ray detectors with a detection limit of 13 nanograys per second, which is about 400 times lower than typical medical imaging doses. We show that these colour-tunable perovskite nanocrystal scintillators can provide a convenient visualization tool for X-ray radiography, as the associated image can be directly recorded by standard digital cameras. We also demonstrate their direct integration with commercial flat-panel imagers and their utility in examining electronic circuit boards under low-dose X-ray illumination.}, } @article {pmid30150771, year = {2018}, author = {Ho, CM and Beck, JR and Lai, M and Cui, Y and Goldberg, DE and Egea, PF and Zhou, ZH}, title = {Malaria parasite translocon structure and mechanism of effector export.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {70-75}, doi = {10.1038/s41586-018-0469-4}, pmid = {30150771}, issn = {1476-4687}, support = {R00 HL133453/HL/NHLBI NIH HHS/United States ; T32 AI007323/AI/NIAID NIH HHS/United States ; R01 AI094386/AI/NIAID NIH HHS/United States ; S10 OD018111/OD/NIH HHS/United States ; U24 GM116792/GM/NIGMS NIH HHS/United States ; R01 GM071940/GM/NIGMS NIH HHS/United States ; R01 DE025567/DE/NIDCR NIH HHS/United States ; S10 RR023057/RR/NCRR NIH HHS/United States ; R21 AI125983/AI/NIAID NIH HHS/United States ; }, abstract = {The putative Plasmodium translocon of exported proteins (PTEX) is essential for transport of malarial effector proteins across a parasite-encasing vacuolar membrane into host erythrocytes, but the mechanism of this process remains unknown. Here we show that PTEX is a bona fide translocon by determining structures of the PTEX core complex at near-atomic resolution using cryo-electron microscopy. We isolated the endogenous PTEX core complex containing EXP2, PTEX150 and HSP101 from Plasmodium falciparum in the 'engaged' and 'resetting' states of endogenous cargo translocation using epitope tags inserted using the CRISPR-Cas9 system. In the structures, EXP2 and PTEX150 interdigitate to form a static, funnel-shaped pseudo-seven-fold-symmetric protein-conducting channel spanning the vacuolar membrane. The spiral-shaped AAA+ HSP101 hexamer is tethered above this funnel, and undergoes pronounced compaction that allows three of six tyrosine-bearing pore loops lining the HSP101 channel to dissociate from the cargo, resetting the translocon for the next threading cycle. Our work reveals the mechanism of P. falciparum effector export, and will inform structure-based design of drugs targeting this unique translocon.}, } @article {pmid30150744, year = {2018}, author = {Barlow, A and Cahill, JA and Hartmann, S and Theunert, C and Xenikoudakis, G and Fortes, GG and Paijmans, JLA and Rabeder, G and Frischauf, C and Grandal-d'Anglade, A and García-Vázquez, A and Murtskhvaladze, M and Saarma, U and Anijalg, P and Skrbinšek, T and Bertorelle, G and Gasparian, B and Bar-Oz, G and Pinhasi, R and Slatkin, M and Dalén, L and Shapiro, B and Hofreiter, M}, title = {Partial genomic survival of cave bears in living brown bears.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1563-1570}, doi = {10.1038/s41559-018-0654-8}, pmid = {30150744}, issn = {2397-334X}, abstract = {Although many large mammal species went extinct at the end of the Pleistocene epoch, their DNA may persist due to past episodes of interspecies admixture. However, direct empirical evidence of the persistence of ancient alleles remains scarce. Here, we present multifold coverage genomic data from four Late Pleistocene cave bears (Ursus spelaeus complex) and show that cave bears hybridized with brown bears (Ursus arctos) during the Pleistocene. We develop an approach to assess both the directionality and relative timing of gene flow. We find that segments of cave bear DNA still persist in the genomes of living brown bears, with cave bears contributing 0.9 to 2.4% of the genomes of all brown bears investigated. Our results show that even though extinction is typically considered as absolute, following admixture, fragments of the gene pool of extinct species can survive for tens of thousands of years in the genomes of extant recipient species.}, } @article {pmid30150743, year = {2018}, author = {Johnston, ASA and Sibly, RM}, title = {The influence of soil communities on the temperature sensitivity of soil respiration.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1597-1602}, doi = {10.1038/s41559-018-0648-6}, pmid = {30150743}, issn = {2397-334X}, abstract = {Soil respiration represents a major carbon flux between terrestrial ecosystems and the atmosphere, and is expected to accelerate under climate warming. Despite its importance in climate change forecasts, however, our understanding of the effects of temperature on soil respiration (RS) is incomplete. Using a metabolic ecology approach we link soil biota metabolism, community composition and heterotrophic activity to predict RS rates across five biomes. We find that accounting for the ecological mechanisms underpinning decomposition processes predicts climatological RS variations observed in an independent dataset (n = 312). The importance of community composition is evident because without it RS is substantially underestimated. With increasing temperature, we predict a latitudinal increase in RS temperature sensitivity, with Q10 values ranging between 2.33 ± 0.01 in tropical forests to 2.72 ± 0.03 in tundra. This global trend has been widely observed, but has not previously been linked to soil communities.}, } @article {pmid30150742, year = {2018}, author = {Mizuuchi, R and Ichihashi, N}, title = {Sustainable replication and coevolution of cooperative RNAs in an artificial cell-like system.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1654-1660}, doi = {10.1038/s41559-018-0650-z}, pmid = {30150742}, issn = {2397-334X}, abstract = {Cooperation among independently replicating molecules is a key phenomenon that allowed the development of complexity during the early evolution of life. Generally, this process is vulnerable to parasitic or selfish entities, which can easily appear and destroy such cooperation. It remains unclear how this fragile cooperation process appeared and has been sustained through evolution. Theoretical studies have indicated that spatial structures, such as compartments, allow sustainable replication and the evolution of cooperative replication, although this has yet to be confirmed experimentally. In this study, we constructed a molecular cooperative replication system, in which two types of RNA, encoding replication or metabolic enzymes, cooperate for their replication in compartments, and we performed long-term replication experiments to examine the sustainability and evolution of the RNAs. We demonstrate that the cooperative relationship of the two RNAs could be sustained at a certain range of RNA concentrations, even when parasitic RNA appeared in the system. We also found that more efficient cooperative RNA replication evolved during long-term replication through seemingly selfish evolution of each RNA. Our results provide experimental evidence supporting the sustainability and robustness of molecular cooperation on an evolutionary timescale.}, } @article {pmid30150741, year = {2018}, author = {Solé, R}, title = {Cooperation in an RNA world.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1527-1528}, doi = {10.1038/s41559-018-0649-5}, pmid = {30150741}, issn = {2397-334X}, } @article {pmid30150740, year = {2018}, author = {Craven, D and Eisenhauer, N and Pearse, WD and Hautier, Y and Isbell, F and Roscher, C and Bahn, M and Beierkuhnlein, C and Bönisch, G and Buchmann, N and Byun, C and Catford, JA and Cerabolini, BEL and Cornelissen, JHC and Craine, JM and De Luca, E and Ebeling, A and Griffin, JN and Hector, A and Hines, J and Jentsch, A and Kattge, J and Kreyling, J and Lanta, V and Lemoine, N and Meyer, ST and Minden, V and Onipchenko, V and Polley, HW and Reich, PB and van Ruijven, J and Schamp, B and Smith, MD and Soudzilovskaia, NA and Tilman, D and Weigelt, A and Wilsey, B and Manning, P}, title = {Multiple facets of biodiversity drive the diversity-stability relationship.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1579-1587}, doi = {10.1038/s41559-018-0647-7}, pmid = {30150740}, issn = {2397-334X}, abstract = {A substantial body of evidence has demonstrated that biodiversity stabilizes ecosystem functioning over time in grassland ecosystems. However, the relative importance of different facets of biodiversity underlying the diversity-stability relationship remains unclear. Here we use data from 39 grassland biodiversity experiments and structural equation modelling to investigate the roles of species richness, phylogenetic diversity and both the diversity and community-weighted mean of functional traits representing the 'fast-slow' leaf economics spectrum in driving the diversity-stability relationship. We found that high species richness and phylogenetic diversity stabilize biomass production via enhanced asynchrony in the performance of co-occurring species. Contrary to expectations, low phylogenetic diversity enhances ecosystem stability directly, albeit weakly. While the diversity of fast-slow functional traits has a weak effect on ecosystem stability, communities dominated by slow species enhance ecosystem stability by increasing mean biomass production relative to the standard deviation of biomass over time. Our in-depth, integrative assessment of factors influencing the diversity-stability relationship demonstrates a more multicausal relationship than has been previously acknowledged.}, } @article {pmid30150735, year = {2019}, author = {Shaw, WR and Catteruccia, F}, title = {Vector biology meets disease control: using basic research to fight vector-borne diseases.}, journal = {Nature microbiology}, volume = {4}, number = {1}, pages = {20-34}, doi = {10.1038/s41564-018-0214-7}, pmid = {30150735}, issn = {2058-5276}, abstract = {Human pathogens that are transmitted by insects are a global problem, particularly those vectored by mosquitoes; for example, malaria parasites transmitted by Anopheles species, and viruses such as dengue, Zika and chikungunya that are carried by Aedes mosquitoes. Over the past 15 years, the prevalence of malaria has been substantially reduced and virus outbreaks have been contained by controlling mosquito vectors using insecticide-based approaches. However, disease control is now threatened by alarming rates of insecticide resistance in insect populations, prompting the need to develop a new generation of specific strategies that can reduce vector-mediated transmission. Here, we review how increased knowledge in insect biology and insect-pathogen interactions is stimulating new concepts and tools for vector control. We focus on strategies that either interfere with the development of pathogens within their vectors or directly impact insect survival, including enhancement of vector-mediated immune control, manipulation of the insect microbiome, or use of powerful new genetic tools such as CRISPR-Cas systems to edit vector genomes. Finally, we offer a perspective on the implementation hurdles as well as the knowledge gaps that must be filled in the coming years to safely realize the potential of these novel strategies to eliminate the scourge of vector-borne disease.}, } @article {pmid30150734, year = {2018}, author = {Goldstein, T and Anthony, SJ and Gbakima, A and Bird, BH and Bangura, J and Tremeau-Bravard, A and Belaganahalli, MN and Wells, HL and Dhanota, JK and Liang, E and Grodus, M and Jangra, RK and DeJesus, VA and Lasso, G and Smith, BR and Jambai, A and Kamara, BO and Kamara, S and Bangura, W and Monagin, C and Shapira, S and Johnson, CK and Saylors, K and Rubin, EM and Chandran, K and Lipkin, WI and Mazet, JAK}, title = {The discovery of Bombali virus adds further support for bats as hosts of ebolaviruses.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1084-1089}, doi = {10.1038/s41564-018-0227-2}, pmid = {30150734}, issn = {2058-5276}, support = {R25 GM104547/GM/NIGMS NIH HHS/United States ; }, abstract = {Here we describe the complete genome of a new ebolavirus, Bombali virus (BOMV) detected in free-tailed bats in Sierra Leone (little free-tailed (Chaerephon pumilus) and Angolan free-tailed (Mops condylurus)). The bats were found roosting inside houses, indicating the potential for human transmission. We show that the viral glycoprotein can mediate entry into human cells. However, further studies are required to investigate whether exposure has actually occurred or if BOMV is pathogenic in humans.}, } @article {pmid30150733, year = {2018}, author = {Garten, M and Nasamu, AS and Niles, JC and Zimmerberg, J and Goldberg, DE and Beck, JR}, title = {EXP2 is a nutrient-permeable channel in the vacuolar membrane of Plasmodium and is essential for protein export via PTEX.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1090-1098}, pmid = {30150733}, issn = {2058-5276}, support = {K99 HL133453/HL/NHLBI NIH HHS/United States ; R00 HL133453/HL/NHLBI NIH HHS/United States ; R01 AI047798/AI/NIAID NIH HHS/United States ; }, abstract = {Intraerythrocytic malaria parasites reside within a parasitophorous vacuolar membrane (PVM) generated during host cell invasion1. Erythrocyte remodelling and parasite metabolism require the export of effector proteins and transport of small molecules across this barrier between the parasite surface and host cell cytosol2,3. Protein export across the PVM is accomplished by the Plasmodium translocon of exported proteins (PTEX) consisting of three core proteins, the AAA+ ATPase HSP101 and two additional proteins known as PTEX150 and EXP24. Inactivation of HSP101 and PTEX150 arrests protein export across the PVM5,6, but the contribution of EXP2 to parasite biology is not well understood7. A nutrient permeable channel in the PVM has also been characterized electrophysiologically, but its molecular identity is unknown8,9. Here, using regulated gene expression, mutagenesis and cell-attached patch-clamp measurements, we show that EXP2, the putative membrane-spanning channel of PTEX4,10-14, serves dual roles as a protein-conducting channel in the context of PTEX and as a channel able to facilitate nutrient passage across the PVM independent of HSP101. Our data suggest a dual functionality for a channel operating in its endogenous context.}, } @article {pmid30150732, year = {2018}, author = {Cohen-Dvashi, H and Kilimnik, I and Diskin, R}, title = {Structural basis for receptor recognition by Lujo virus.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1153-1160}, doi = {10.1038/s41564-018-0224-5}, pmid = {30150732}, issn = {2058-5276}, abstract = {Lujo virus (LUJV) has emerged as a highly fatal human pathogen. Despite its membership among the Arenaviridae, LUJV does not classify with the known Old and New World groups of that viral family. Likewise, LUJV was recently found to use neuropilin-2 (NRP2) as a cellular receptor instead of the canonical receptors used by Old World and New World arenaviruses. The emergence of a deadly pathogen into human populations using an unprecedented entry route raises many questions regarding the mechanism of cell recognition. To provide the basis for combating LUJV in particular, and to increase our general understanding of the molecular changes that accompany an evolutionary switch to a new receptor for arenaviruses, we used X-ray crystallography to reveal how the GP1 receptor-binding domain of LUJV (LUJVGP1) recognizes NRP2. Structural data show that LUJVGP1 is more similar to Old World than to New World arenaviruses. Structural analysis supported by experimental validation further suggests that NRP2 recognition is metal-ion dependent and that the complete NRP2 binding site is formed in the context of the trimeric spike. Taken together, our data provide the mechanism for the cell attachment step of LUJV and present indispensable information for combating this phatogen.}, } @article {pmid30150660, year = {2018}, author = {Miao, D and Margolis, CA and Vokes, NI and Liu, D and Taylor-Weiner, A and Wankowicz, SM and Adeegbe, D and Keliher, D and Schilling, B and Tracy, A and Manos, M and Chau, NG and Hanna, GJ and Polak, P and Rodig, SJ and Signoretti, S and Sholl, LM and Engelman, JA and Getz, G and Jänne, PA and Haddad, RI and Choueiri, TK and Barbie, DA and Haq, R and Awad, MM and Schadendorf, D and Hodi, FS and Bellmunt, J and Wong, KK and Hammerman, P and Van Allen, EM}, title = {Genomic correlates of response to immune checkpoint blockade in microsatellite-stable solid tumors.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1271-1281}, pmid = {30150660}, issn = {1546-1718}, support = {K08 CA188615/CA/NCI NIH HHS/United States ; R01 CA140594/CA/NCI NIH HHS/United States ; R01 CA166480/CA/NCI NIH HHS/United States ; }, abstract = {Tumor mutational burden correlates with response to immune checkpoint blockade in multiple solid tumors, although in microsatellite-stable tumors this association is of uncertain clinical utility. Here we uniformly analyzed whole-exome sequencing (WES) of 249 tumors and matched normal tissue from patients with clinically annotated outcomes to immune checkpoint therapy, including radiographic response, across multiple cancer types to examine additional tumor genomic features that contribute to selective response. Our analyses identified genomic correlates of response beyond mutational burden, including somatic events in individual driver genes, certain global mutational signatures, and specific HLA-restricted neoantigens. However, these features were often interrelated, highlighting the complexity of identifying genetic driver events that generate an immunoresponsive tumor environment. This study lays a path forward in analyzing large clinical cohorts in an integrated and multifaceted manner to enhance the ability to discover clinically meaningful predictive features of response to immune checkpoint blockade.}, } @article {pmid30150418, year = {2018}, author = {Ene, IV and Farrer, RA and Hirakawa, MP and Agwamba, K and Cuomo, CA and Bennett, RJ}, title = {Global analysis of mutations driving microevolution of a heterozygous diploid fungal pathogen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8688-E8697}, pmid = {30150418}, issn = {1091-6490}, support = {HHSN272200900018C/AI/NIAID NIH HHS/United States ; R21 AI112363/AI/NIAID NIH HHS/United States ; R21 AI122011/AI/NIAID NIH HHS/United States ; R21 AI139592/AI/NIAID NIH HHS/United States ; //Wellcome Trust/United Kingdom ; F31 DE023726/DE/NIDCR NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; R01 AI081704/AI/NIAID NIH HHS/United States ; }, mesh = {Candida albicans/*genetics/growth & development ; Candidiasis/microbiology ; Chromosomes, Fungal ; *Diploidy ; *Evolution, Molecular ; Genome, Fungal/genetics ; Heterozygote ; Humans ; Loss of Heterozygosity ; *Mutation ; Selection, Genetic ; }, abstract = {Candida albicans is a heterozygous diploid yeast that is a commensal of the human gastrointestinal tract and a prevalent opportunistic pathogen. Here, whole-genome sequencing was performed on multiple C. albicans isolates passaged both in vitro and in vivo to characterize the complete spectrum of mutations arising in laboratory culture and in the mammalian host. We establish that, independent of culture niche, microevolution is primarily driven by de novo base substitutions and frequent short-tract loss-of-heterozygosity events. An average base-substitution rate of ∼1.2 × 10-10 per base pair per generation was observed in vitro, with higher rates inferred during host infection. Large-scale chromosomal changes were relatively rare, although chromosome 7 trisomies frequently emerged during passaging in a gastrointestinal model and was associated with increased fitness for this niche. Multiple chromosomal features impacted mutational patterns, with mutation rates elevated in repetitive regions, subtelomeric regions, and in gene families encoding cell surface proteins involved in host adhesion. Strikingly, de novo mutation rates were more than 800-fold higher in regions immediately adjacent to emergent loss-of-heterozygosity tracts, indicative of recombination-induced mutagenesis. Furthermore, genomes showed biased patterns of mutations suggestive of extensive purifying selection during passaging. These results reveal how both cell-intrinsic and cell-extrinsic factors influence C. albicans microevolution, and provide a quantitative picture of genome dynamics in this heterozygous diploid species.}, } @article {pmid30150417, year = {2018}, author = {Wolf, YI and Katsnelson, MI and Koonin, EV}, title = {Physical foundations of biological complexity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8678-E8687}, pmid = {30150417}, issn = {1091-6490}, mesh = {*Algorithms ; Animals ; *Biological Evolution ; *Biological Phenomena ; Cell Communication ; Computer Simulation ; Humans ; *Models, Biological ; *Physical Phenomena ; }, abstract = {Biological systems reach hierarchical complexity that has no counterpart outside the realm of biology. Undoubtedly, biological entities obey the fundamental physical laws. Can today's physics provide an explanatory framework for understanding the evolution of biological complexity? We argue that the physical foundation for understanding the origin and evolution of complexity can be gleaned at the interface between the theory of frustrated states resulting in pattern formation in glass-like media and the theory of self-organized criticality (SOC). On the one hand, SOC has been shown to emerge in spin-glass systems of high dimensionality. On the other hand, SOC is often viewed as the most appropriate physical description of evolutionary transitions in biology. We unify these two faces of SOC by showing that emergence of complex features in biological evolution typically, if not always, is triggered by frustration that is caused by competing interactions at different organizational levels. Such competing interactions lead to SOC, which represents the optimal conditions for the emergence of complexity. Competing interactions and frustrated states permeate biology at all organizational levels and are tightly linked to the ubiquitous competition for limiting resources. This perspective extends from the comparatively simple phenomena occurring in glasses to large-scale events of biological evolution, such as major evolutionary transitions. Frustration caused by competing interactions in multidimensional systems could be the general driving force behind the emergence of complexity, within and beyond the domain of biology.}, } @article {pmid30150416, year = {2018}, author = {Tang, H and Chang, H and Dong, Y and Guo, L and Shi, X and Wu, Y and Huang, Y and He, Y}, title = {Architecture of cell-cell adhesion mediated by sidekicks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9246-9251}, pmid = {30150416}, issn = {1091-6490}, mesh = {Animals ; Cell Adhesion/physiology ; *Cell Membrane/chemistry/metabolism/ultrastructure ; *Electron Microscope Tomography ; HEK293 Cells ; Humans ; *Immunoglobulin G/chemistry/metabolism/ultrastructure ; *Membrane Proteins/chemistry/metabolism/ultrastructure ; Mice ; Protein Domains ; }, abstract = {Cell-cell adhesion is important for cell growth, tissue development, and neural network formation. Structures of cell adhesion molecules have been widely studied by crystallography, revealing the molecular details of adhesion interfaces. However, due to technical limitations, the overall structure and organization of adhesion molecules at cell adhesion interfaces has not been fully investigated. Here, we combine electron microscopy and other biophysical methods to characterize the structure of cell-cell adhesion mediated by the cell adhesion molecule Sidekick (Sidekick-1 and Sidekick-2) and obtain 3D views of the Sidekick-mediated adhesion interfaces as well as the organization of Sidekick molecules between cell membranes by electron tomography. The results suggest that the Ig-like domains and the fibronectin III (FnIII) domains of Sidekicks play different roles in cell adhesion. The Ig-like domains mediate the homophilic transinteractions bridging adjacent cells, while the FnIII domains interact with membranes, resulting in a tight adhesion interface between cells that may contribute to the specificity and plasticity of cell-cell contacts during cell growth and neural development.}, } @article {pmid30150415, year = {2018}, author = {Rivas-Pardo, JA and Badilla, CL and Tapia-Rojo, R and Alonso-Caballero, Á and Fernández, JM}, title = {Molecular strategy for blocking isopeptide bond formation in nascent pilin proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9222-9227}, pmid = {30150415}, issn = {1091-6490}, support = {R01 GM116122/GM/NIGMS NIH HHS/United States ; R01 HL061228/HL/NHLBI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*chemistry/pharmacology ; Fimbriae Proteins/*antagonists & inhibitors/*chemistry/metabolism ; Humans ; Peptides/*chemistry/pharmacology ; Protein Domains ; *Protein Folding ; Protein Stability ; Streptococcus pyogenes/*chemistry/metabolism/pathogenicity ; }, abstract = {Bacteria anchor to their host cells through their adhesive pili, which must resist the large mechanical stresses induced by the host as it attempts to dislodge the pathogens. The pili of gram-positive bacteria are constructed as a single polypeptide made of hundreds of pilin repeats, which contain intramolecular isopeptide bonds strategically located in the structure to prevent their unfolding under force, protecting the pilus from degradation by extant proteases and oxygen radicals. Here, we demonstrate the design of a short peptide that blocks the formation of the isopeptide bond present in the pilin Spy0128 from the human pathogen Streptococcus pyogenes, resulting in mechanically labile pilin domains. We use a combination of protein engineering and atomic-force microscopy force spectroscopy to demonstrate that the peptide blocks the formation of the native isopeptide bond and compromises the mechanics of the domain. While an intact Spy0128 is inextensible at any force, peptide-modified Spy0128 pilins readily unfold at very low forces, marking the abrogation of the intramolecular isopeptide bond as well as the absence of a stable pilin fold. We propose that isopeptide-blocking peptides could be further developed as a type of highly specific antiadhesive antibiotics to treat gram-positive pathogens.}, } @article {pmid30150414, year = {2018}, author = {Espinoza-Sanchez, S and Metskas, LA and Chou, SZ and Rhoades, E and Pollard, TD}, title = {Conformational changes in Arp2/3 complex induced by ATP, WASp-VCA, and actin filaments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8642-E8651}, pmid = {30150414}, issn = {1091-6490}, support = {R01 GM026338/GM/NIGMS NIH HHS/United States ; R01 NS079955/NS/NINDS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/chemistry/*metabolism ; Actin-Related Protein 2-3 Complex/chemistry/genetics/*metabolism ; Adenosine Triphosphate/chemistry/*metabolism ; Fluorescence Resonance Energy Transfer ; Microscopy, Electron, Transmission ; Mutation ; Protein Binding ; Protein Conformation ; Schizosaccharomyces/genetics/metabolism ; Schizosaccharomyces pombe Proteins/chemistry/genetics/*metabolism ; Wiskott-Aldrich Syndrome Protein/chemistry/*metabolism ; }, abstract = {We used fluorescence spectroscopy and EM to determine how binding of ATP, nucleation-promoting factors, actin monomers, and actin filaments changes the conformation of Arp2/3 complex during the process that nucleates an actin filament branch. We mutated subunits of Schizosaccharomyces pombe Arp2/3 complex for labeling with fluorescent dyes at either the C termini of Arp2 and Arp3 or ArpC1 and ArpC3. We measured Förster resonance energy transfer (FRET) efficiency (ETeff) between the dyes in the presence of the various ligands. We also computed class averages from electron micrographs of negatively stained specimens. ATP binding made small conformational changes of the nucleotide-binding cleft of the Arp2 subunit. WASp-VCA, WASp-CA, and WASp-actin-VCA changed the ETeff between the dyes on the Arp2 and Arp3 subunits much more than between dyes on ArpC1 and ArpC3. Ensemble FRET detected an additional structural change that brought ArpC1 and ArpC3 closer together when Arp2/3 complex bound actin filaments. VCA binding to Arp2/3 complex causes a conformational change that favors binding to the side of an actin filament, which allows further changes required to nucleate a daughter filament.}, } @article {pmid30150413, year = {2018}, author = {Ngeow, KC and Friedrichsen, HJ and Li, L and Zeng, Z and Andrews, S and Volpon, L and Brunsdon, H and Berridge, G and Picaud, S and Fischer, R and Lisle, R and Knapp, S and Filippakopoulos, P and Knowles, H and Steingrímsson, E and Borden, KLB and Patton, EE and Goding, CR}, title = {BRAF/MAPK and GSK3 signaling converges to control MITF nuclear export.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8668-E8677}, pmid = {30150413}, issn = {1091-6490}, support = {095751/Z/11/Z//Wellcome Trust/United Kingdom ; R01 CA080728/CA/NCI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; C38302/A12981//Cancer Research UK/United Kingdom ; MC_PC_U127585840//Medical Research Council/United Kingdom ; MP/19200//Arthritis Research UK/United Kingdom ; }, mesh = {Active Transport, Cell Nucleus ; Animals ; Cell Line, Tumor ; Cell Nucleus/*metabolism ; Cells, Cultured ; Glycogen Synthase Kinase 3/*metabolism ; HeLa Cells ; Humans ; *MAP Kinase Signaling System ; Melanoma/genetics/metabolism/pathology ; Microphthalmia-Associated Transcription Factor/genetics/*metabolism ; Mutation ; Phosphorylation ; Protein Binding ; Proto-Oncogene Proteins B-raf/*metabolism ; }, abstract = {The close integration of the MAPK, PI3K, and WNT signaling pathways underpins much of development and is deregulated in cancer. In principle, combinatorial posttranslational modification of key lineage-specific transcription factors would be an effective means to integrate critical signaling events. Understanding how this might be achieved is central to deciphering the impact of microenvironmental cues in development and disease. The microphthalmia-associated transcription factor MITF plays a crucial role in the development of melanocytes, the retinal pigment epithelium, osteoclasts, and mast cells and acts as a lineage survival oncogene in melanoma. MITF coordinates survival, differentiation, cell-cycle progression, cell migration, metabolism, and lysosome biogenesis. However, how the activity of this key transcription factor is controlled remains poorly understood. Here, we show that GSK3, downstream from both the PI3K and Wnt pathways, and BRAF/MAPK signaling converges to control MITF nuclear export. Phosphorylation of the melanocyte MITF-M isoform in response to BRAF/MAPK signaling primes for phosphorylation by GSK3, a kinase inhibited by both PI3K and Wnt signaling. Dual phosphorylation, but not monophosphorylation, then promotes MITF nuclear export by activating a previously unrecognized hydrophobic export signal. Nonmelanocyte MITF isoforms exhibit poor regulation by MAPK signaling, but instead their export is controlled by mTOR. We uncover here an unanticipated mode of MITF regulation that integrates the output of key developmental and cancer-associated signaling pathways to gate MITF flux through the import-export cycle. The results have significant implications for our understanding of melanoma progression and stem cell renewal.}, } @article {pmid30150412, year = {2018}, author = {Vardi, N and Chaturvedi, S and Weinberger, LS}, title = {Feedback-mediated signal conversion promotes viral fitness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8803-E8810}, pmid = {30150412}, issn = {1091-6490}, support = {DP2 OD006677/OD/NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; }, mesh = {Cell Line ; Cells, Cultured ; Cytomegalovirus/*genetics/physiology ; *Feedback, Physiological ; *Gene Expression Regulation, Viral ; Host-Pathogen Interactions ; Humans ; Immediate-Early Proteins/genetics/metabolism ; Microscopy, Fluorescence ; Retinal Pigment Epithelium/cytology/virology ; Time-Lapse Imaging/methods ; Virus Replication/*genetics ; }, abstract = {A fundamental signal-processing problem is how biological systems maintain phenotypic states (i.e., canalization) long after degradation of initial catalyst signals. For example, to efficiently replicate, herpesviruses (e.g., human cytomegalovirus, HCMV) rapidly counteract cell-mediated silencing using transactivators packaged in the tegument of the infecting virion particle. However, the activity of these tegument transactivators is inherently transient-they undergo immediate proteolysis but delayed synthesis-and how transient activation sustains lytic viral gene expression despite cell-mediated silencing is unclear. By constructing a two-color, conditional-feedback HCMV mutant, we find that positive feedback in HCMV's immediate-early 1 (IE1) protein is of sufficient strength to sustain HCMV lytic expression. Single-cell time-lapse imaging and mathematical modeling show that IE1 positive feedback converts transient transactivation signals from tegument pp71 proteins into sustained lytic expression, which is obligate for efficient viral replication, whereas attenuating feedback decreases fitness by promoting a reversible silenced state. Together, these results identify a regulatory mechanism enabling herpesviruses to sustain expression despite transient activation signals-akin to early electronic transistors-and expose a potential target for therapeutic intervention.}, } @article {pmid30150411, year = {2018}, author = {Madsen, JJ and Grime, JMA and Rossman, JS and Voth, GA}, title = {Entropic forces drive clustering and spatial localization of influenza A M2 during viral budding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8595-E8603}, pmid = {30150411}, issn = {1091-6490}, support = {R01 GM063796/GM/NIGMS NIH HHS/United States ; MR/L00870X/1//Medical Research Council/United Kingdom ; MR/L018578/1//Medical Research Council/United Kingdom ; }, mesh = {Algorithms ; Animals ; Cell Membrane/chemistry/ultrastructure/*virology ; Dogs ; Entropy ; Host-Pathogen Interactions ; Madin Darby Canine Kidney Cells ; Membrane Lipids/chemistry ; Microscopy, Electron ; Models, Biological ; Molecular Dynamics Simulation ; Viral Matrix Proteins/*physiology ; *Virus Assembly ; *Virus Release ; }, abstract = {The influenza A matrix 2 (M2) transmembrane protein facilitates virion release from the infected host cell. In particular, M2 plays a role in the induction of membrane curvature and/or in the scission process whereby the envelope is cut upon virion release. Here we show using coarse-grained computer simulations that various M2 assembly geometries emerge due to an entropic driving force, resulting in compact clusters or linearly extended aggregates as a direct consequence of the lateral membrane stresses. Conditions under which these protein assemblies will cause the lipid membrane to curve are explored, and we predict that a critical cluster size is required for this to happen. We go on to demonstrate that under the stress conditions taking place in the cellular membrane as it undergoes large-scale membrane remodeling, the M2 protein will, in principle, be able to both contribute to curvature induction and sense curvature to line up in manifolds where local membrane line tension is high. M2 is found to exhibit linactant behavior in liquid-disordered-liquid-ordered phase-separated lipid mixtures and to be excluded from the liquid-ordered phase, in near-quantitative agreement with experimental observations. Our findings support a role for M2 in membrane remodeling during influenza viral budding both as an inducer and a sensor of membrane curvature, and they suggest a mechanism by which localization of M2 can occur as the virion assembles and releases from the host cell, independent of how the membrane curvature is produced.}, } @article {pmid30150410, year = {2018}, author = {Toptan, T and Abere, B and Nalesnik, MA and Swerdlow, SH and Ranganathan, S and Lee, N and Shair, KH and Moore, PS and Chang, Y}, title = {Circular DNA tumor viruses make circular RNAs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8737-E8745}, pmid = {30150410}, issn = {1091-6490}, support = {P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA170354/CA/NCI NIH HHS/United States ; R35 CA197463/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; DNA Tumor Viruses/*genetics ; Epstein-Barr Virus Infections/virology ; *Gene Expression Regulation, Viral ; Herpesvirus 4, Human/genetics ; Herpesvirus 8, Human/genetics ; Humans ; Lymphoma/virology ; RNA/*genetics ; RNA, Viral/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sarcoma, Kaposi/virology ; }, abstract = {Epstein-Barr virus (EBV) and Kaposi's sarcoma herpesvirus (KSHV) cause ∼2% of all human cancers. RNase R-resistant RNA sequencing revealed that both gammaherpesviruses encode multiple, uniquely stable, circular RNAs (circRNA). EBV abundantly expressed both exon-only and exon-intron circRNAs from the BamHI A rightward transcript (BART) locus (circBARTs) formed from a spliced BART transcript and excluding the EBV miRNA region. The circBARTs were expressed in all verified EBV latency types, including EBV-positive posttransplant lymphoproliferative disease, Burkitt lymphoma, nasopharyngeal carcinoma, and AIDS-associated lymphoma tissues and cell lines. Only cells infected with the B95-8 EBV strain, with a 12-kb BART locus deletion, were negative for EBV circBARTs. Less abundant levels of EBV circRNAs originating from LMP2- and BHLF1-encoding genes were also identified. The circRNA sequencing of KSHV-infected primary effusion lymphoma cells revealed a KSHV-encoded circRNA from the vIRF4 locus (circvIRF4) that was constitutively expressed. In addition, KSHV polyadenylated nuclear (PAN) RNA locus generated a swarm (>100) of multiply backspliced, low-abundance RNase R-resistant circRNAs originating in both sense and antisense directions consistent with a novel hyperbacksplicing mechanism. In EBV and KSHV coinfected cells, exon-only EBV circBARTs were located more in the cytoplasm, whereas the intron-retaining circBARTs were found in the nuclear fraction. KSHV circvIRF4 and circPANs were detected in both nuclear and cytoplasmic fractions. Among viral circRNAs tested, none were found in polysome fractions from KSHV-EBV coinfected BC1 cells, although low-abundance protein translation from viral circRNAs could not be excluded. The circRNAs are a new class of viral transcripts expressed in gammaherpesvirus-related tumors that might contribute to viral oncogenesis.}, } @article {pmid30150409, year = {2018}, author = {Stolz, JF and Basu, P}, title = {Unraveling the inner workings of respiratory arsenate reductase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9051-9053}, pmid = {30150409}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Arsenate Reductases/*genetics ; Ion Pumps/genetics ; *Operon ; }, } @article {pmid30150408, year = {2018}, author = {Li, X and Ding, P and Rubin, DB}, title = {Asymptotic theory of rerandomization in treatment-control experiments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9157-9162}, pmid = {30150408}, issn = {1091-6490}, support = {R01 AI102710/AI/NIAID NIH HHS/United States ; }, mesh = {*Models, Theoretical ; *Random Allocation ; }, abstract = {Although complete randomization ensures covariate balance on average, the chance of observing significant differences between treatment and control covariate distributions increases with many covariates. Rerandomization discards randomizations that do not satisfy a predetermined covariate balance criterion, generally resulting in better covariate balance and more precise estimates of causal effects. Previous theory has derived finite sample theory for rerandomization under the assumptions of equal treatment group sizes, Gaussian covariate and outcome distributions, or additive causal effects, but not for the general sampling distribution of the difference-in-means estimator for the average causal effect. We develop asymptotic theory for rerandomization without these assumptions, which reveals a non-Gaussian asymptotic distribution for this estimator, specifically a linear combination of a Gaussian random variable and truncated Gaussian random variables. This distribution follows because rerandomization affects only the projection of potential outcomes onto the covariate space but does not affect the corresponding orthogonal residuals. We demonstrate that, compared with complete randomization, rerandomization reduces the asymptotic quantile ranges of the difference-in-means estimator. Moreover, our work constructs accurate large-sample confidence intervals for the average causal effect.}, } @article {pmid30150407, year = {2018}, author = {Moss, FR and Shuken, SR and Mercer, JAM and Cohen, CM and Weiss, TM and Boxer, SG and Burns, NZ}, title = {Ladderane phospholipids form a densely packed membrane with normal hydrazine and anomalously low proton/hydroxide permeability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9098-9103}, pmid = {30150407}, issn = {1091-6490}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; R01 GM069630/GM/NIGMS NIH HHS/United States ; R35 GM118044/GM/NIGMS NIH HHS/United States ; }, mesh = {Anaerobiosis/physiology ; Bacteria/*chemistry/metabolism ; Cell Membrane/*chemistry/metabolism ; *Cell Membrane Permeability ; Hydrazines/*chemistry/metabolism ; Hydroxides/*chemistry/metabolism ; Phospholipids/*chemistry/metabolism ; *Protons ; }, abstract = {Ladderane lipids are unique to anaerobic ammonium-oxidizing (anammox) bacteria and are enriched in the membrane of the anammoxosome, an organelle thought to compartmentalize the anammox process, which involves the toxic intermediate hydrazine (N2H4). Due to the slow growth rate of anammox bacteria and difficulty of isolating pure ladderane lipids, experimental evidence of the biological function of ladderanes is lacking. We have synthesized two natural and one unnatural ladderane phosphatidylcholine lipids and compared their thermotropic properties in self-assembled bilayers to distinguish between [3]- and [5]-ladderane function. We developed a hydrazine transmembrane diffusion assay using a water-soluble derivative of a hydrazine sensor and determined that ladderane membranes are as permeable to hydrazine as straight-chain lipid bilayers. However, pH equilibration across ladderane membranes occurs 5-10 times more slowly than across straight-chain lipid membranes. Langmuir monolayer analysis and the rates of fluorescence recovery after photobleaching suggest that dense ladderane packing may preclude formation of proton/hydroxide-conducting water wires. These data support the hypothesis that ladderanes prevent the breakdown of the proton motive force rather than blocking hydrazine transmembrane diffusion in anammox bacteria.}, } @article {pmid30150406, year = {2018}, author = {Bohk-Ewald, C and Li, P and Myrskylä, M}, title = {Forecast accuracy hardly improves with method complexity when completing cohort fertility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9187-9192}, pmid = {30150406}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Cohort Studies ; *Databases, Factual ; Female ; *Fertility ; Humans ; *Models, Biological ; *Population Forecast ; Predictive Value of Tests ; }, abstract = {Forecasts of completed fertility predict how many children will be born on average by women over their entire reproductive lifetime. These forecasts are important in informing public policy and influencing additional research in the social sciences. However, nothing is known about how to choose a forecasting method from a large basket of variants. We identified 20 major methods, with 162 variants altogether. The approaches range from naive freezing of current age-specific fertility rates to methods that use statistically sophisticated techniques or are grounded in demographic theory. We assess each method by evaluating the overall accuracy and if provided, uncertainty estimates using fertility data of all available birth cohorts and countries of the Human Fertility Database, which covers 1,096 birth cohorts from 29 countries. Across multiple measures of forecast accuracy, we find only four methods that consistently outperform the naive freeze rates method, and only two methods produce uncertainty estimates that are not severely downward biased. Among the top four, there are two simple extrapolation methods and two Bayesian methods. The latter are demanding in terms of input data, statistical techniques, and computational power but do not consistently complete cohort fertility more accurately at all truncation ages than simple extrapolation. This broad picture is unchanged if we base the validation on 201 United Nations countries and six world regions, including Africa, Asia, Europe, Latin America and the Caribbean, northern America, and Oceania.}, } @article {pmid30150405, year = {2018}, author = {Sonntag, R and Giebeler, N and Nevzorova, YA and Bangen, JM and Fahrenkamp, D and Lambertz, D and Haas, U and Hu, W and Gassler, N and Cubero, FJ and Müller-Newen, G and Abdallah, AT and Weiskirchen, R and Ticconi, F and Costa, IG and Barbacid, M and Trautwein, C and Liedtke, C}, title = {Cyclin E1 and cyclin-dependent kinase 2 are critical for initiation, but not for progression of hepatocellular carcinoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9282-9287}, pmid = {30150405}, issn = {1091-6490}, mesh = {Animals ; Carcinoma, Hepatocellular/genetics/*metabolism/pathology ; Cell Transformation, Neoplastic/genetics/*metabolism/pathology ; Cyclin E/*biosynthesis/genetics ; Cyclin-Dependent Kinase 2/*biosynthesis/genetics ; Cyclins/biosynthesis/genetics ; *DNA Repair ; *Gene Expression Regulation, Neoplastic ; Liver Neoplasms/genetics/*metabolism/pathology ; Mice ; Mice, Knockout ; Oncogene Proteins/*biosynthesis/genetics ; }, abstract = {E-type cyclins E1 (CcnE1) and E2 (CcnE2) are regulatory subunits of cyclin-dependent kinase 2 (Cdk2) and thought to control the transition of quiescent cells into the cell cycle. Initial findings indicated that CcnE1 and CcnE2 have largely overlapping functions for cancer development in several tumor entities including hepatocellular carcinoma (HCC). In the present study, we dissected the differential contributions of CcnE1, CcnE2, and Cdk2 for initiation and progression of HCC in mice and patients. To this end, we tested the HCC susceptibility in mice with constitutive deficiency for CcnE1 or CcnE2 as well as in mice lacking Cdk2 in hepatocytes. Genetic inactivation of CcnE1 largely prevented development of liver cancer in mice in two established HCC models, while ablation of CcnE2 had no effect on hepatocarcinogenesis. Importantly, CcnE1-driven HCC initiation was dependent on Cdk2. However, isolated primary hepatoma cells typically acquired independence on CcnE1 and Cdk2 with increasing progression in vitro, which was associated with a gene signature involving secondary induction of CcnE2 and up-regulation of cell cycle and DNA repair pathways. Importantly, a similar expression profile was also found in HCC patients with elevated CcnE2 expression and poor survival. In general, overall survival in HCC patients was synergistically affected by expression of CcnE1 and CcnE2, but not through Cdk2. Our study suggests that HCC initiation specifically depends on CcnE1 and Cdk2, while HCC progression requires expression of any E-cyclin, but no Cdk2.}, } @article {pmid30150404, year = {2018}, author = {McDermott, GR and Meng, KC and McDonald, GG and Costello, CJ}, title = {The blue paradox: Preemptive overfishing in marine reserves.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802862115}, pmid = {30150404}, issn = {1091-6490}, abstract = {Most large-scale conservation policies are anticipated or announced in advance. This risks the possibility of preemptive resource extraction before the conservation intervention goes into force. We use a high-resolution dataset of satellite-based fishing activity to show that anticipation of an impending no-take marine reserve undermines the policy by triggering an unintended race-to-fish. We study one of the world's largest marine reserves, the Phoenix Islands Protected Area (PIPA), and find that fishers more than doubled their fishing effort once this area was earmarked for eventual protected status. The additional fishing effort resulted in an impoverished starting point for PIPA equivalent to 1.5 y of banned fishing. Extrapolating this behavior globally, we estimate that if other marine reserve announcements were to trigger similar preemptive fishing, this could temporarily increase the share of overextracted fisheries from 65% to 72%. Our findings have implications for general conservation efforts as well as the methods that scientists use to monitor and evaluate policy efficacy.}, } @article {pmid30150403, year = {2018}, author = {Wang, S and Herzog, ED and Kiss, IZ and Schwartz, WJ and Bloch, G and Sebek, M and Granados-Fuentes, D and Wang, L and Li, JS}, title = {Inferring dynamic topology for decoding spatiotemporal structures in complex heterogeneous networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9300-9305}, pmid = {30150403}, issn = {1091-6490}, support = {R01 GM094109/GM/NIGMS NIH HHS/United States ; R21 EY027590/EY/NEI NIH HHS/United States ; U01 EB021956/EB/NIBIB NIH HHS/United States ; }, mesh = {*Models, Theoretical ; }, abstract = {Extracting complex interactions (i.e., dynamic topologies) has been an essential, but difficult, step toward understanding large, complex, and diverse systems including biological, financial, and electrical networks. However, reliable and efficient methods for the recovery or estimation of network topology remain a challenge due to the tremendous scale of emerging systems (e.g., brain and social networks) and the inherent nonlinearity within and between individual units. We develop a unified, data-driven approach to efficiently infer connections of networks (ICON). We apply ICON to determine topology of networks of oscillators with different periodicities, degree nodes, coupling functions, and time scales, arising in silico, and in electrochemistry, neuronal networks, and groups of mice. This method enables the formulation of these large-scale, nonlinear estimation problems as a linear inverse problem that can be solved using parallel computing. Working with data from networks, ICON is robust and versatile enough to reliably reveal full and partial resonance among fast chemical oscillators, coherent circadian rhythms among hundreds of cells, and functional connectivity mediating social synchronization of circadian rhythmicity among mice over weeks.}, } @article {pmid30150402, year = {2018}, author = {Kono, M and Yoshida, N and Maeda, K and Skinner, NE and Pan, W and Kyttaris, VC and Tsokos, MG and Tsokos, GC}, title = {Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9288-9293}, pmid = {30150402}, issn = {1091-6490}, support = {R37 AI049954/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Catalytic Domain ; *Cell Differentiation ; Cyclic AMP Response Element Modulator/genetics/immunology/metabolism ; Encephalomyelitis, Autoimmune, Experimental/enzymology/genetics/immunology/pathology ; Female ; *Gene Expression Regulation, Enzymologic ; Humans ; Lupus Erythematosus, Systemic/enzymology/genetics/immunology/pathology ; Male ; Mice ; Mice, Knockout ; Phosphoprotein Phosphatases/*biosynthesis/genetics/immunology ; *Response Elements ; Th17 Cells/*enzymology/immunology/pathology ; }, abstract = {Th17 cells favor glycolytic metabolism, and pyruvate dehydrogenase (PDH) is the key bifurcation enzyme, which in its active dephosphorylated form advances the oxidative phosphorylation from glycolytic pathway. The transcriptional factor, inducible cAMP early repressor/cAMP response element modulator (ICER/CREM), has been shown to be induced in Th17 cells and to be overexpressed in CD4+ T cells from the patients with systemic lupus erythematosus (SLE). We found that glycolysis and lactate production in in vitro Th17-polarized T cells was reduced and that the expression of pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2), an enzyme that converts the inactive PDH to its active form, and PDH enzyme activity were increased in Th17 cells from ICER/CREM-deficient animals. ICER was found to bind to the Pdp2 promoter and suppress its expression. Furthermore, forced expression of PDP2 in CD4+ cells reduced the in vitro Th17 differentiation, whereas shRNA-based suppression of PDP2 expression increased in vitro Th17 differentiation and augmented experimental autoimmune encephalomyelitis. At the translational level, PDP2 expression was decreased in memory Th17 cells from patients with SLE and forced expression of PDP2 in CD4+ T cells from lupus-prone MRL/lpr mice and patients with SLE suppressed Th17 differentiation. These data demonstrate the direct control of energy production during Th17 differentiation in health and disease by the transcription factor ICER/CREM at the PDH metabolism bifurcation level.}, } @article {pmid30150401, year = {2018}, author = {Summers, DW and Milbrandt, J and DiAntonio, A}, title = {Palmitoylation enables MAPK-dependent proteostasis of axon survival factors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8746-E8754}, pmid = {30150401}, issn = {1091-6490}, support = {R01 CA219866/CA/NCI NIH HHS/United States ; R01 NS065053/NS/NINDS NIH HHS/United States ; R01 NS087632/NS/NINDS NIH HHS/United States ; RF1 AG013730/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Armadillo Domain Proteins/metabolism ; Axons/*metabolism ; Cell Survival/drug effects ; Cells, Cultured ; Cytoskeletal Proteins/metabolism ; HEK293 Cells ; Humans ; Lipoylation ; MAP Kinase Kinase Kinases/antagonists & inhibitors/*metabolism ; MAP Kinase Signaling System/drug effects/*physiology ; Mice ; Nerve Degeneration/prevention & control ; Neurons/cytology/metabolism ; Nicotinamide-Nucleotide Adenylyltransferase/metabolism ; Piperazines/pharmacology ; Proteostasis/*physiology ; }, abstract = {Axon degeneration is a prominent event in many neurodegenerative disorders. Axon injury stimulates an intrinsic self-destruction program that culminates in activation of the prodegeneration factor SARM1 and local dismantling of damaged axon segments. In healthy axons, SARM1 activity is restrained by constant delivery of the axon survival factor NMNAT2. Elevating NMNAT2 is neuroprotective, while loss of NMNAT2 evokes SARM1-dependent axon degeneration. As a gatekeeper of axon survival, NMNAT2 abundance is an important regulatory node in neuronal health, highlighting the need to understand the mechanisms behind NMNAT2 protein homeostasis. We demonstrate that pharmacological inhibition of the MAP3Ks dual leucine zipper kinase (DLK) and leucine zipper kinase (LZK) elevates NMNAT2 abundance and strongly protects axons from injury-induced degeneration. We discover that MAPK signaling selectively promotes degradation of palmitoylated NMNAT2, as well as palmitoylated SCG10. Conversely, nonpalmitoylated NMNAT2 is degraded by the Phr1/Skp1a/Fbxo45 ligase complex. Combined inactivation of both pathways leads to synergistic accumulation of NMNAT2 in axons and dramatically enhanced protection against pathological axon degeneration. Hence, the subcellular localization of distinct pools of NMNAT2 enables differential regulation of NMNAT2 abundance to control axon survival.}, } @article {pmid30150400, year = {2018}, author = {Chang, ACY and Chang, ACH and Kirillova, A and Sasagawa, K and Su, W and Weber, G and Lin, J and Termglinchan, V and Karakikes, I and Seeger, T and Dainis, AM and Hinson, JT and Seidman, J and Seidman, CE and Day, JW and Ashley, E and Wu, JC and Blau, HM}, title = {Telomere shortening is a hallmark of genetic cardiomyopathies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9276-9281}, pmid = {30150400}, issn = {1091-6490}, support = {R01 HL130020/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R21 AG044815/AG/NIA NIH HHS/United States ; R01 HL123968/HL/NHLBI NIH HHS/United States ; R24 HL117756/HL/NHLBI NIH HHS/United States ; K08 HL125807/HL/NHLBI NIH HHS/United States ; R00 HL104002/HL/NHLBI NIH HHS/United States ; K99 HL104002/HL/NHLBI NIH HHS/United States ; 201411MFE-338745-169197//CIHR/Canada ; T32 GM007790/GM/NIGMS NIH HHS/United States ; R01 HL126527/HL/NHLBI NIH HHS/United States ; R01 AR063963/AR/NIAMS NIH HHS/United States ; }, mesh = {*Cardiomyopathy, Dilated/genetics/metabolism/pathology ; *Cardiomyopathy, Hypertrophic, Familial/genetics/metabolism/pathology ; *Cell Division ; Female ; Humans ; *Induced Pluripotent Stem Cells/metabolism/pathology ; Male ; *Muscle Proteins/genetics/metabolism ; *Mutation ; *Telomere Shortening ; }, abstract = {This study demonstrates that significantly shortened telomeres are a hallmark of cardiomyocytes (CMs) from individuals with end-stage hypertrophic cardiomyopathy (HCM) or dilated cardiomyopathy (DCM) as a result of heritable defects in cardiac proteins critical to contractile function. Positioned at the ends of chromosomes, telomeres are DNA repeats that serve as protective caps that shorten with each cell division, a marker of aging. CMs are a known exception in which telomeres remain relatively stable throughout life in healthy individuals. We found that, relative to healthy controls, telomeres are significantly shorter in CMs of genetic HCM and DCM patient tissues harboring pathogenic mutations: TNNI3, MYBPC3, MYH7, DMD, TNNT2, and TTN Quantitative FISH (Q-FISH) of single cells revealed that telomeres were significantly reduced by 26% in HCM and 40% in DCM patient CMs in fixed tissue sections compared with CMs from age- and sex-matched healthy controls. In the cardiac tissues of the same patients, telomere shortening was not evident in vascular smooth muscle cells that do not express or require the contractile proteins, an important control. Telomere shortening was recapitulated in DCM and HCM CMs differentiated from patient-derived human-induced pluripotent stem cells (hiPSCs) measured by two independent assays. This study reveals telomere shortening as a hallmark of genetic HCM and DCM and demonstrates that this shortening can be modeled in vitro by using the hiPSC platform, enabling drug discovery.}, } @article {pmid30150399, year = {2018}, author = {Chapkin, KD and Bursi, L and Stec, GJ and Lauchner, A and Hogan, NJ and Cui, Y and Nordlander, P and Halas, NJ}, title = {Lifetime dynamics of plasmons in the few-atom limit.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9134-9139}, pmid = {30150399}, issn = {1091-6490}, abstract = {Polycyclic aromatic hydrocarbon (PAH) molecules are essentially graphene in the subnanometer limit, typically consisting of 50 or fewer atoms. With the addition or removal of a single electron, these molecules can support molecular plasmon (collective) resonances in the visible region of the spectrum. Here, we probe the plasmon dynamics in these quantum systems by measuring the excited-state lifetime of three negatively charged PAH molecules: anthanthrene, benzo[ghi]perylene, and perylene. In contrast to the molecules in their neutral state, these three systems exhibit far more rapid decay dynamics due to the deexcitation of multiple electron-hole pairs through molecular plasmon "dephasing" and vibrational relaxation. This study provides a look into the distinction between collective and single-electron excitation dynamics in the purely quantum limit and introduces a conceptual framework with which to visualize molecular plasmon decay.}, } @article {pmid30150398, year = {2018}, author = {Arvanitis, CD and Askoxylakis, V and Guo, Y and Datta, M and Kloepper, J and Ferraro, GB and Bernabeu, MO and Fukumura, D and McDannold, N and Jain, RK}, title = {Mechanisms of enhanced drug delivery in brain metastases with focused ultrasound-induced blood-tumor barrier disruption.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8717-E8726}, pmid = {30150398}, issn = {1091-6490}, support = {P01 CA174645/CA/NCI NIH HHS/United States ; F31 HL126449/HL/NHLBI NIH HHS/United States ; U01 CA224348/CA/NCI NIH HHS/United States ; R01 CA129371/CA/NCI NIH HHS/United States ; R35 CA197743/CA/NCI NIH HHS/United States ; P01 CA080124/CA/NCI NIH HHS/United States ; R01 CA208205/CA/NCI NIH HHS/United States ; R00 EB016971/EB/NIBIB NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Combined Chemotherapy Protocols/*administration & dosage/pharmacokinetics ; Blood-Brain Barrier/*drug effects/metabolism ; Brain/diagnostic imaging/metabolism/pathology ; Brain Neoplasms/*drug therapy/metabolism/secondary ; Breast Neoplasms/drug therapy/metabolism/pathology ; Cell Line, Tumor ; Doxorubicin/administration & dosage/pharmacokinetics ; Drug Delivery Systems/*methods ; Humans ; Maytansine/administration & dosage/analogs & derivatives/pharmacokinetics ; Mice ; Microbubbles ; Trastuzumab/administration & dosage/pharmacokinetics ; Ultrasonography/methods ; Xenograft Model Antitumor Assays ; }, abstract = {Blood-brain/blood-tumor barriers (BBB and BTB) and interstitial transport may constitute major obstacles to the transport of therapeutics in brain tumors. In this study, we examined the impact of focused ultrasound (FUS) in combination with microbubbles on the transport of two relevant chemotherapy-based anticancer agents in breast cancer brain metastases at cellular resolution: doxorubicin, a nontargeted chemotherapeutic, and ado-trastuzumab emtansine (T-DM1), an antibody-drug conjugate. Using an orthotopic xenograft model of HER2-positive breast cancer brain metastasis and quantitative microscopy, we demonstrate significant increases in the extravasation of both agents (sevenfold and twofold for doxorubicin and T-DM1, respectively), and we provide evidence of increased drug penetration (>100 vs. <20 µm and 42 ± 7 vs. 12 ± 4 µm for doxorubicin and T-DM1, respectively) after the application of FUS compared with control (non-FUS). Integration of experimental data with physiologically based pharmacokinetic (PBPK) modeling of drug transport reveals that FUS in combination with microbubbles alleviates vascular barriers and enhances interstitial convective transport via an increase in hydraulic conductivity. Experimental data demonstrate that FUS in combination with microbubbles enhances significantly the endothelial cell uptake of the small chemotherapeutic agent. Quantification with PBPK modeling reveals an increase in transmembrane transport by more than two orders of magnitude. PBPK modeling indicates a selective increase in transvascular transport of doxorubicin through small vessel wall pores with a narrow range of sizes (diameter, 10-50 nm). Our work provides a quantitative framework for the optimization of FUS-drug combinations to maximize intratumoral drug delivery and facilitate the development of strategies to treat brain metastases.}, } @article {pmid30150397, year = {2018}, author = {Mohan, D and Fischhoff, B and Angus, DC and Rosengart, MR and Wallace, DJ and Yealy, DM and Farris, C and Chang, CH and Kerti, S and Barnato, AE}, title = {Serious games may improve physician heuristics in trauma triage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9204-9209}, pmid = {30150397}, issn = {1091-6490}, support = {DP2 LM012339/LM/NLM NIH HHS/United States ; K08 HL122478/HL/NHLBI NIH HHS/United States ; }, mesh = {Education, Medical, Continuing/*methods ; Female ; Humans ; Male ; *Triage ; United States ; *Video Games ; *Wounds and Injuries ; }, abstract = {Trauma triage depends on fallible human judgment. We created two "serious" video game training interventions to improve that judgment. The interventions' central theoretical construct was the representativeness heuristic, which, in trauma triage, would mean judging the severity of an injury by how well it captures (or "represents") the key features of archetypes of cases requiring transfer to a trauma center. Drawing on clinical experience, medical records, and an expert panel, we identified features characteristic of representative and nonrepresentative cases. The two interventions instantiated both kinds of cases. One was an adventure game, seeking narrative engagement; the second was a puzzle-based game, emphasizing analogical reasoning. Both incorporated feedback on diagnostic errors, explaining their sources and consequences. In a four-arm study, they were compared with an intervention using traditional text-based continuing medical education materials (active control) and a no-intervention (passive control) condition. A sample of 320 physicians working at nontrauma centers in the United States was recruited and randomized to a study arm. The primary outcome was performance on a validated virtual simulation, measured as the proportion of undertriaged patients, defined as ones who had severe injuries (according to American College of Surgeons guidelines) but were not transferred. Compared with the control group, physicians exposed to either game undertriaged fewer such patients [difference = -18%, 95% CI: -30 to -6%, P = 0.002 (adventure game); -17%, 95% CI: -28 to -6%, P = 0.003 (puzzle game)]; those exposed to the text-based education undertriaged similar proportions (difference = +8%, 95% CI: -3 to +19%, P = 0.15).}, } @article {pmid30150396, year = {2018}, author = {Zhu, F and Feng, M and Sinha, R and Seita, J and Mori, Y and Weissman, IL}, title = {Screening for genes that regulate the differentiation of human megakaryocytic lineage cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {E9308-E9316}, pmid = {30150396}, issn = {1091-6490}, support = {R00 CA201075/CA/NCI NIH HHS/United States ; R01 CA086065/CA/NCI NIH HHS/United States ; U01 HL099999/HL/NHLBI NIH HHS/United States ; }, mesh = {Blood Platelets/cytology/*metabolism ; CRISPR-Cas Systems ; Cell Differentiation/*physiology ; Cell Line ; Humans ; Megakaryocyte Progenitor Cells/cytology ; }, abstract = {Different combinations of transcription factors (TFs) function at each stage of hematopoiesis, leading to distinct expression patterns of lineage-specific genes. The identification of such regulators and their functions in hematopoiesis remain largely unresolved. In this study, we utilized screening approaches to study the transcriptional regulators of megakaryocyte progenitor (MkP) generation, a key step before platelet production. Promising candidate genes were generated from a microarray platform gene expression commons and individually manipulated in human hematopoietic stem and progenitor cells (HSPCs). Deletion of some of the candidate genes (the hit genes) by CRISPR/Cas9 led to decreased MkP generation during HSPC differentiation, while more MkPs were produced when some hit genes were overexpressed in HSPCs. We then demonstrated that overexpression of these genes can increase the frequency of mature megakaryocytic colonies by functional colony forming unit-megakaryocyte (CFU-Mk) assay and the release of platelets after in vitro maturation. Finally, we showed that the histone deacetylase inhibitors could also increase MkP differentiation, possibly by regulating some of the newly identified TFs. Therefore, identification of such regulators will advance the understanding of basic mechanisms of HSPC differentiation and conceivably enable the generation and maturation of megakaryocytes and platelets in vitro.}, } @article {pmid30150395, year = {2018}, author = {}, title = {Correction to Supporting Information for Potting et al., Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8579}, doi = {10.1073/pnas.1813216115}, pmid = {30150395}, issn = {1091-6490}, } @article {pmid30150394, year = {2018}, author = {Zambrana, JV and Bustos Carrillo, F and Burger-Calderon, R and Collado, D and Sanchez, N and Ojeda, S and Carey Monterrey, J and Plazaola, M and Lopez, B and Arguello, S and Elizondo, D and Aviles, W and Coloma, J and Kuan, G and Balmaseda, A and Gordon, A and Harris, E}, title = {Seroprevalence, risk factor, and spatial analyses of Zika virus infection after the 2016 epidemic in Managua, Nicaragua.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9294-9299}, pmid = {30150394}, issn = {1091-6490}, support = {P01 AI106695/AI/NIAID NIH HHS/United States ; R01 AI099631/AI/NIAID NIH HHS/United States ; R01 AI120997/AI/NIAID NIH HHS/United States ; R21 AI121721/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Child ; Child, Preschool ; *Epidemics ; Female ; Humans ; Male ; Nicaragua/epidemiology ; Risk Factors ; Seroepidemiologic Studies ; Sex Factors ; *Zika Virus ; Zika Virus Infection/*epidemiology ; }, abstract = {In 2015, a Zika epidemic in Brazil began spreading throughout the Americas. Zika virus (ZIKV) entered Managua, Nicaragua, in January 2016 and caused an epidemic that peaked in July-September 2016. ZIKV seropositivity was estimated among participants of pediatric (n = 3,740) and household (n = 2,147) cohort studies, including an adult-only subset from the household cohort (n = 1,074), in Managua. Seropositivity was based on a highly sensitive and specific assay, the Zika NS1 blockade-of-binding ELISA, which can be used in dengue-endemic populations. Overall seropositivity for the pediatric (ages 2-14), household (ages 2-80), and adult (ages 15-80) cohorts was 36, 46, and 56%, respectively. Trend, risk factor, and contour mapping analyses demonstrated that ZIKV seroprevalence increased nonlinearly with age and that body surface area was statistically associated with increasing seroprevalence in children. ZIKV seropositivity was higher in females than in males across almost all ages, with adjusted prevalence ratios in children and adults of 1.11 (95% CI: 1.02-1.21) and 1.14 (95% CI: 1.01-1.28), respectively. No household-level risk factors were statistically significant in multivariate analyses. A spatial analysis revealed a 10-15% difference in the risk of ZIKV infections across our 3-km-wide study site, suggesting that ZIKV infection risk varies at small spatial scales. To our knowledge, this is the largest ZIKV seroprevalence study reported in the Americas, and the only one in Central America and in children to date. It reveals a high level of immunity against ZIKV in Managua as a result of the 2016 epidemic, making a second large Zika epidemic unlikely in the near future.}, } @article {pmid30150393, year = {2018}, author = {Sormaz, M and Murphy, C and Wang, HT and Hymers, M and Karapanagiotidis, T and Poerio, G and Margulies, DS and Jefferies, E and Smallwood, J}, title = {Default mode network can support the level of detail in experience during active task states.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9318-9323}, pmid = {30150393}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Cognition/*physiology ; Emotions/*physiology ; Female ; Humans ; Male ; Memory, Short-Term/*physiology ; Motor Cortex/*physiology ; Nerve Net/*physiology ; }, abstract = {Regions of transmodal cortex, in particular the default mode network (DMN), have historically been argued to serve functions unrelated to task performance, in part because of associations with naturally occurring periods of off-task thought. In contrast, contemporary views of the DMN suggest it plays an integrative role in cognition that emerges from its location at the top of a cortical hierarchy and its relative isolation from systems directly involved in perception and action. The combination of these topographical features may allow the DMN to support abstract representations derived from lower levels in the hierarchy and so reflect the broader cognitive landscape. To investigate these contrasting views of DMN function, we sampled experience as participants performed tasks varying in their working-memory load while inside an fMRI scanner. We used self-report data to establish dimensions of thought that describe levels of detail, the relationship to a task, the modality of thought, and its emotional qualities. We used representational similarity analysis to examine correspondences between patterns of neural activity and each dimension of thought. Our results were inconsistent with a task-negative view of DMN function. Distinctions between on- and off-task thought were associated with patterns of consistent neural activity in regions adjacent to unimodal cortex, including motor and premotor cortex. Detail in ongoing thought was associated with patterns of activity within the DMN during periods of working-memory maintenance. These results demonstrate a contribution of the DMN to ongoing cognition extending beyond task-unrelated processing that can include detailed experiences occurring under active task conditions.}, } @article {pmid30150392, year = {2018}, author = {Zhang, Y and He, X and Zhuo, R and Sha, R and Brujic, J and Seeman, NC and Chaikin, PM}, title = {Multivalent, multiflavored droplets by design.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9086-9091}, pmid = {30150392}, issn = {1091-6490}, abstract = {Nature self-assembles functional materials by programming flexible linear arrangements of molecules and then folding them to make 2D and 3D objects. To understand and emulate this process, we have made emulsion droplets with specific recognition and controlled valence. Uniquely monovalent droplets form dimers: divalent lead to polymer-like chains, trivalent allow for branching, and programmed mixtures of different valences enable a variety of designed architectures and the ability to subsequently close and open structures. Our functional building blocks are a hybrid of micrometer-scale emulsion droplets and nanoscale DNA origami technologies. Functional DNA origami rafts are first added to droplets and then herded into a patch using specifically designated "shepherding" rafts. Additional patches with the same or different specificities can be formed on the same droplet, programming multiflavored, multivalence droplets. The mobile patch can bind to a patch on another droplet containing complementary functional rafts, leading to primary structure formation. Further binding of nonneighbor droplets can produce secondary structures, a third step in hierarchical self-assembly. The use of mobile patches rather than uniform DNA coverage has the advantage of valence control at the expense of slow kinetics. Droplets with controlled flavors and valences enable a host of different material and device architectures.}, } @article {pmid30150391, year = {2018}, author = {Lai, CSW and Adler, A and Gan, WB}, title = {Fear extinction reverses dendritic spine formation induced by fear conditioning in the mouse auditory cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9306-9311}, pmid = {30150391}, issn = {1091-6490}, support = {R01 NS047325/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Auditory Cortex/cytology/*physiology ; Dendritic Spines/*physiology ; Fear/*physiology ; Male ; Mice, Transgenic ; Nerve Net/cytology/*physiology ; }, abstract = {Fear conditioning-induced behavioral responses can be extinguished after fear extinction. While fear extinction is generally thought to be a form of new learning, several lines of evidence suggest that neuronal changes associated with fear conditioning could be reversed after fear extinction. To better understand how fear conditioning and extinction modify synaptic circuits, we examined changes of postsynaptic dendritic spines of layer V pyramidal neurons in the mouse auditory cortex over time using transcranial two-photon microscopy. We found that auditory-cued fear conditioning induced the formation of new dendritic spines within 2 days. The survived new spines induced by fear conditioning with one auditory cue were clustered within dendritic branch segments and spatially segregated from new spines induced by fear conditioning with a different auditory cue. Importantly, fear extinction preferentially caused the elimination of newly formed spines induced by fear conditioning in an auditory cue-specific manner. Furthermore, after fear extinction, fear reconditioning induced reformation of new dendritic spines in close proximity to the sites of new spine formation induced by previous fear conditioning. These results show that fear conditioning, extinction, and reconditioning induce cue- and location-specific dendritic spine remodeling in the auditory cortex. They also suggest that changes of synaptic connections induced by fear conditioning are reversed after fear extinction.}, } @article {pmid30150390, year = {2018}, author = {Watarai, A and Arai, N and Miyawaki, S and Okano, H and Miura, K and Mogi, K and Kikusui, T}, title = {Responses to pup vocalizations in subordinate naked mole-rats are induced by estradiol ingested through coprophagy of queen's feces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9264-9269}, pmid = {30150390}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; Coprophagia/*physiology ; Mole Rats/*physiology ; *Social Behavior ; Vocalization, Animal/*physiology ; }, abstract = {Naked mole-rats form eusocial colonies consisting of a single breeding female (the queen), several breeding males, and sexually immature adults (subordinates). Subordinates are cooperative and provide alloparental care by huddling and retrieving pups to the nest. However, the physiological mechanism(s) underlying alloparental behavior of nonbreeders remains undetermined. Here, we examined the response of subordinates to pup voice and the fecal estradiol concentrations of subordinates during the three reproductive periods of the queen, including gestation, postpartum, and nonlactating. Subordinate response to pup voice was observed only during the queen's postpartum and was preceded by an incremental rise in subordinates' fecal estradiol concentrations during the queen's gestation period, which coincided with physiological changes in the queen. We hypothesized that the increased estradiol in the queen's feces was disseminated to subordinates through coprophagy, which stimulated subordinates' responses to pup vocalizations. To test this hypothesis, we fed subordinates either fecal pellets from pregnant queens or pellets from nonpregnant queens amended with estradiol for 9 days and examined their response to recorded pup voice. In both treatments, the subordinates exhibited a constant level of response to pup voice during the feeding period but became more responsive 4 days after the feeding period. Thus, we believe that we have identified a previously unknown system of communication in naked mole-rats, in which a hormone released by one individual controls the behavior of another individual and influences the level of responsiveness among subordinate adults to pup vocal signals, thereby contributing to the alloparental pup care by subordinates.}, } @article {pmid30150389, year = {2018}, author = {Wang, J and Niu, J and Yan, B and Li, X and Bi, R and Yao, Y and Yu, D and Wu, X}, title = {Vanishing quantum oscillations in Dirac semimetal ZrTe5.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9145-9150}, pmid = {30150389}, issn = {1091-6490}, abstract = {One of the characteristics of topological materials is their nontrivial Berry phase. Experimental determination of this phase largely relies on a phase analysis of quantum oscillations. We study the angular dependence of the oscillations in a Dirac material [Formula: see text] and observe a striking spin-zero effect (i.e., vanishing oscillations accompanied with a phase inversion). This indicates that the Berry phase in [Formula: see text] remains nontrivial for arbitrary field direction, in contrast with previous reports. The Zeeman splitting is found to be proportional to the magnetic field based on the condition for the spin-zero effect in a Dirac band. Moreover, it is suggested that the Dirac band in [Formula: see text] is likely transformed into a line node other than Weyl points for the field directions at which the spin zero occurs. The results underline a largely overlooked spin factor when determining the Berry phase from quantum oscillations.}, } @article {pmid30150388, year = {2018}, author = {Staubwasser, M and Drăgușin, V and Onac, BP and Assonov, S and Ersek, V and Hoffmann, DL and Veres, D}, title = {Impact of climate change on the transition of Neanderthals to modern humans in Europe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9116-9121}, pmid = {30150388}, issn = {1091-6490}, mesh = {Animals ; *Archaeology ; *Climate Change ; Europe ; *Extinction, Biological ; History, Ancient ; Humans ; *Neanderthals ; }, abstract = {Two speleothem stable isotope records from East-Central Europe demonstrate that Greenland Stadial 12 (GS12) and GS10-at 44.3-43.3 and 40.8-40.2 ka-were prominent intervals of cold and arid conditions. GS12, GS11, and GS10 are coeval with a regional pattern of culturally (near-)sterile layers within Europe's diachronous archeologic transition from Neanderthals to modern human Aurignacian. Sterile layers coeval with GS12 precede the Aurignacian throughout the middle and upper Danube region. In some records from the northern Iberian Peninsula, such layers are coeval with GS11 and separate the Châtelperronian from the Aurignacian. Sterile layers preceding the Aurignacian in the remaining Châtelperronian domain are coeval with GS10 and the previously reported 40.0- to 40.8-ka cal BP [calendar years before present (1950)] time range of Neanderthals' disappearance from most of Europe. This suggests that ecologic stress during stadial expansion of steppe landscape caused a diachronous pattern of depopulation of Neanderthals, which facilitated repopulation by modern humans who appear to have been better adapted to this environment. Consecutive depopulation-repopulation cycles during severe stadials of the middle pleniglacial may principally explain the repeated replacement of Europe's population and its genetic composition.}, } @article {pmid30150387, year = {2018}, author = {Haller, G and Karrasch, D and Kogelbauer, F}, title = {Material barriers to diffusive and stochastic transport.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9074-9079}, pmid = {30150387}, issn = {1091-6490}, abstract = {We seek transport barriers and transport enhancers as material surfaces across which the transport of diffusive tracers is minimal or maximal in a general, unsteady flow. We find that such surfaces are extremizers of a universal, nondimensional transport functional whose leading-order term in the diffusivity can be computed directly from the flow velocity. The most observable (uniform) transport extremizers are explicitly computable as null surfaces of an objective transport tensor. Even in the limit of vanishing diffusivity, these surfaces differ from all previously identified coherent structures for purely advective fluid transport. Our results extend directly to stochastic velocity fields and hence enable transport barrier and enhancer detection under uncertainties.}, } @article {pmid30150386, year = {2018}, author = {Agozzino, L and Dill, KA}, title = {Protein evolution speed depends on its stability and abundance and on chaperone concentrations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9092-9097}, pmid = {30150386}, issn = {1091-6490}, mesh = {*Evolution, Molecular ; *Models, Genetic ; *Protein Folding ; Proteins/*chemistry/*genetics ; }, abstract = {Proteins evolve at different rates. What drives the speed of protein sequence changes? Two main factors are a protein's folding stability and aggregation propensity. By combining the hydrophobic-polar (HP) model with the Zwanzig-Szabo-Bagchi rate theory, we find that: (i) Adaptation is strongly accelerated by selection pressure, explaining the broad variation from days to thousands of years over which organisms adapt to new environments. (ii) The proteins that adapt fastest are those that are not very stably folded, because their fitness landscapes are steepest. And because heating destabilizes folded proteins, we predict that cells should adapt faster when put into warmer rather than cooler environments. (iii) Increasing protein abundance slows down evolution (the substitution rate of the sequence) because a typical protein is not perfectly fit, so increasing its number of copies reduces the cell's fitness. (iv) However, chaperones can mitigate this abundance effect and accelerate evolution (also called evolutionary capacitance) by effectively enhancing protein stability. This model explains key observations about protein evolution rates.}, } @article {pmid30150385, year = {2018}, author = {Galligan, JJ and Wepy, JA and Streeter, MD and Kingsley, PJ and Mitchener, MM and Wauchope, OR and Beavers, WN and Rose, KL and Wang, T and Spiegel, DA and Marnett, LJ}, title = {Methylglyoxal-derived posttranslational arginine modifications are abundant histone marks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9228-9233}, pmid = {30150385}, issn = {1091-6490}, support = {U19 HL065962/HL/NHLBI NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 CA087819/CA/NCI NIH HHS/United States ; G20 RR030956/RR/NCRR NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; R37 CA087819/CA/NCI NIH HHS/United States ; P50 GM115305/GM/NIGMS NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; T32 GM065086/GM/NIGMS NIH HHS/United States ; UL1 RR024975/RR/NCRR NIH HHS/United States ; S10 OD017997/OD/NIH HHS/United States ; }, mesh = {Arginine/*metabolism ; HEK293 Cells ; Histones/*metabolism ; Humans ; Lactoylglutathione Lyase/*metabolism ; Protein Processing, Post-Translational/*drug effects ; *Pyruvaldehyde/metabolism/pharmacology ; Transcription, Genetic/*drug effects ; }, abstract = {Histone posttranslational modifications (PTMs) regulate chromatin dynamics, DNA accessibility, and transcription to expand the genetic code. Many of these PTMs are produced through cellular metabolism to offer both feedback and feedforward regulation. Herein we describe the existence of Lys and Arg modifications on histones by a glycolytic by-product, methylglyoxal (MGO). Our data demonstrate that adduction of histones by MGO is an abundant modification, present at the same order of magnitude as Arg methylation. These modifications were detected on all four core histones at critical residues involved in both nucleosome stability and reader domain binding. In addition, MGO treatment of cells lacking the major detoxifying enzyme, glyoxalase 1, results in marked disruption of H2B acetylation and ubiquitylation without affecting H2A, H3, and H4 modifications. Using RNA sequencing, we show that MGO is capable of altering gene transcription, most notably in cells lacking GLO1. Finally, we show that the deglycase DJ-1 protects histones from adduction by MGO. Collectively, our findings demonstrate the existence of a previously undetected histone modification derived from glycolysis, which may have far-reaching implications for the control of gene expression and protein transcription linked to metabolism.}, } @article {pmid30150384, year = {2018}, author = {Sigaki, HYD and Perc, M and Ribeiro, HV}, title = {History of art paintings through the lens of entropy and complexity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8585-E8594}, pmid = {30150384}, issn = {1091-6490}, abstract = {Art is the ultimate expression of human creativity that is deeply influenced by the philosophy and culture of the corresponding historical epoch. The quantitative analysis of art is therefore essential for better understanding human cultural evolution. Here, we present a large-scale quantitative analysis of almost 140,000 paintings, spanning nearly a millennium of art history. Based on the local spatial patterns in the images of these paintings, we estimate the permutation entropy and the statistical complexity of each painting. These measures map the degree of visual order of artworks into a scale of order-disorder and simplicity-complexity that locally reflects qualitative categories proposed by art historians. The dynamical behavior of these measures reveals a clear temporal evolution of art, marked by transitions that agree with the main historical periods of art. Our research shows that different artistic styles have a distinct average degree of entropy and complexity, thus allowing a hierarchical organization and clustering of styles according to these metrics. We have further verified that the identified groups correspond well with the textual content used to qualitatively describe the styles and the applied complexity-entropy measures can be used for an effective classification of artworks.}, } @article {pmid30150383, year = {2018}, author = {Zhang, X and Chen, X and Zhang, X}, title = {The impact of exposure to air pollution on cognitive performance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9193-9197}, pmid = {30150383}, issn = {1091-6490}, support = {K01 AG053408/AG/NIA NIH HHS/United States ; P30 AG021342/AG/NIA NIH HHS/United States ; R03 AG048920/AG/NIA NIH HHS/United States ; }, mesh = {*Air Pollution/adverse effects/economics ; China ; *Cognition ; *Environmental Exposure/adverse effects/economics ; Humans ; *Models, Econometric ; }, abstract = {This paper examines the effect of both cumulative and transitory exposures to air pollution for the same individuals over time on cognitive performance by matching a nationally representative longitudinal survey and air quality data in China according to the exact time and geographic locations of the cognitive tests. We find that long-term exposure to air pollution impedes cognitive performance in verbal and math tests. We provide evidence that the effect of air pollution on verbal tests becomes more pronounced as people age, especially for men and the less educated. The damage on the aging brain by air pollution likely imposes substantial health and economic costs, considering that cognitive functioning is critical for the elderly for both running daily errands and making high-stake decisions.}, } @article {pmid30150382, year = {2018}, author = {Li, X and Harris, CJ and Zhong, Z and Chen, W and Liu, R and Jia, B and Wang, Z and Li, S and Jacobsen, SE and Du, J}, title = {Mechanistic insights into plant SUVH family H3K9 methyltransferases and their binding to context-biased non-CG DNA methylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8793-E8802}, pmid = {30150382}, issn = {1091-6490}, support = {R01 GM060398/GM/NIGMS NIH HHS/United States ; R37 GM060398/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Base Sequence ; Crystallography, X-Ray ; DNA/chemistry/genetics/metabolism ; *DNA Methylation ; Histone-Lysine N-Methyltransferase/chemistry/genetics/*metabolism ; Histones/*metabolism ; Lysine/*metabolism ; Methylation ; Models, Molecular ; Nucleic Acid Conformation ; Plants, Genetically Modified ; Protein Binding ; Protein Conformation ; }, abstract = {DNA methylation functions in gene silencing and the maintenance of genome integrity. In plants, non-CG DNA methylation is linked through a self-reinforcing loop with histone 3 lysine 9 dimethylation (H3K9me2). The plant-specific SUPPRESSOR OF VARIEGATION 3-9 HOMOLOG (SUVH) family H3K9 methyltransferases (MTases) bind to DNA methylation marks and catalyze H3K9 methylation. Here, we analyzed the structure and function of Arabidopsis thaliana SUVH6 to understand how this class of enzyme maintains methylation patterns in the genome. We reveal that SUVH6 has a distinct 5-methyl-dC (5mC) base-flipping mechanism involving a thumb loop element. Autoinhibition of H3 substrate entry is regulated by a SET domain loop, and a conformational transition in the post-SET domain upon cofactor binding may control catalysis. In vitro DNA binding and in vivo ChIP-seq data reveal that the different SUVH family H3K9 MTases have distinct DNA binding preferences, targeting H3K9 methylation to sites with different methylated DNA sequences, explaining the context biased non-CG DNA methylation in plants.}, } @article {pmid30150381, year = {2018}, author = {Mossaad, N and Ferwerda, J and Lawrence, D and Weinstein, JM and Hainmueller, J}, title = {Determinants of refugee naturalization in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9175-9180}, pmid = {30150381}, issn = {1091-6490}, mesh = {*Emigration and Immigration ; Female ; Humans ; Male ; *Refugees ; *Socioeconomic Factors ; United States ; }, abstract = {The United States operates the world's largest refugee resettlement program. However, there is almost no systematic evidence on whether refugees successfully integrate into American society over the long run. We address this gap by drawing on linked administrative data to directly measure a long-term integration outcome: naturalization rates. Assessing the full population of refugees resettled between 2000 and 2010, we find that refugees naturalize at high rates: 66% achieved citizenship by 2015. This rate is substantially higher than among other immigrants who became eligible for citizenship during the same period. We also find significant heterogeneity in naturalization rates. Consistent with the literature on immigration more generally, sociodemographic characteristics condition the likelihood of naturalization. Women, refugees with longer residency, and those with higher education levels are more likely to obtain citizenship. National origins also matter. While refugees from Iran, Iraq, and Somalia naturalize at higher rates, those from Burma, Ukraine, Vietnam, and Liberia naturalize at lower rates. We also find naturalization success is significantly shaped by the initial resettlement location. Placing refugees in areas that are urban, have lower rates of unemployment, and have a larger share of conationals increases the likelihood of acquiring citizenship. These findings suggest pathways to promote refugee integration by targeting interventions and by optimizing the geographic placement of refugees.}, } @article {pmid30150380, year = {2018}, author = {Watkins, AJ and Dias, I and Tsuro, H and Allen, D and Emes, RD and Moreton, J and Wilson, R and Ingram, RJM and Sinclair, KD}, title = {Paternal diet programs offspring health through sperm- and seminal plasma-specific pathways in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {40}, pages = {10064-10069}, pmid = {30150380}, issn = {1091-6490}, mesh = {Animals ; *Dietary Exposure ; Dietary Proteins/*administration & dosage ; Epigenesis, Genetic/drug effects ; Female ; Male ; Mice ; *Paternal Exposure ; Semen/*metabolism ; Semen Analysis ; Spermatozoa/*metabolism ; Testis/*metabolism ; Uterus/metabolism ; }, abstract = {The association between poor paternal diet, perturbed embryonic development, and adult offspring ill health represents a new focus for the Developmental Origins of Health and Disease hypothesis. However, our understanding of the underlying mechanisms remains ill-defined. We have developed a mouse paternal low-protein diet (LPD) model to determine its impact on semen quality, maternal uterine physiology, and adult offspring health. We observed that sperm from LPD-fed male mice displayed global hypomethylation associated with reduced testicular expression of DNA methylation and folate-cycle regulators compared with normal protein diet (NPD) fed males. Furthermore, females mated with LPD males display blunted preimplantation uterine immunological, cell signaling, and vascular remodeling responses compared to controls. These data indicate paternal diet impacts on offspring health through both sperm genomic (epigenetic) and seminal plasma (maternal uterine environment) mechanisms. Extending our model, we defined sperm- and seminal plasma-specific effects on offspring health by combining artificial insemination with vasectomized male mating of dietary-manipulated males. All offspring derived from LPD sperm and/or seminal plasma became heavier with increased adiposity, glucose intolerance, perturbed hepatic gene expression symptomatic of nonalcoholic fatty liver disease, and altered gut bacterial profiles. These data provide insight into programming mechanisms linking poor paternal diet with semen quality and offspring health.}, } @article {pmid30150379, year = {2018}, author = {Bickel, PJ and Kur, G and Nadler, B}, title = {Projection pursuit in high dimensions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9151-9156}, doi = {10.1073/pnas.1801177115}, pmid = {30150379}, issn = {1091-6490}, abstract = {Projection pursuit is a classical exploratory data analysis method to detect interesting low-dimensional structures in multivariate data. Originally, projection pursuit was applied mostly to data of moderately low dimension. Motivated by contemporary applications, we here study its properties in high-dimensional settings. Specifically, we analyze the asymptotic properties of projection pursuit on structureless multivariate Gaussian data with an identity covariance, as both dimension p and sample size n tend to infinity, with [Formula: see text] Our main results are that (i) if [Formula: see text] then there exist projections whose corresponding empirical cumulative distribution function can approximate any arbitrary distribution; and (ii) if [Formula: see text], not all limiting distributions are possible. However, depending on the value of γ, various non-Gaussian distributions may still be approximated. In contrast, if we restrict to sparse projections, involving only a few of the p variables, then asymptotically all empirical cumulative distribution functions are Gaussian. And (iii) if [Formula: see text], then asymptotically all projections are Gaussian. Some of these results extend to mean-centered sub-Gaussian data and to projections into k dimensions. Hence, in the "small n, large p" setting, unless sparsity is enforced, and regardless of the chosen projection index, projection pursuit may detect an apparent structure that has no statistical significance. Furthermore, our work reveals fundamental limitations on the ability to detect non-Gaussian signals in high-dimensional data, in particular through independent component analysis and related non-Gaussian component analysis.}, } @article {pmid30150378, year = {2018}, author = {Siebzehnrübl, FA and Raber, KA and Urbach, YK and Schulze-Krebs, A and Canneva, F and Moceri, S and Habermeyer, J and Achoui, D and Gupta, B and Steindler, DA and Stephan, M and Nguyen, HP and Bonin, M and Riess, O and Bauer, A and Aigner, L and Couillard-Despres, S and Paucar, MA and Svenningsson, P and Osmand, A and Andreew, A and Zabel, C and Weiss, A and Kuhn, R and Moussaoui, S and Blockx, I and Van der Linden, A and Cheong, RY and Roybon, L and Petersén, Å and von Hörsten, S}, title = {Early postnatal behavioral, cellular, and molecular changes in models of Huntington disease are reversible by HDAC inhibition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8765-E8774}, pmid = {30150378}, issn = {1091-6490}, support = {R01 NS055165/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Cell Differentiation/*drug effects/genetics/physiology ; Disease Models, Animal ; Female ; Histone Deacetylase Inhibitors/pharmacology ; Humans ; Huntingtin Protein/genetics ; Huntington Disease/genetics/*physiopathology ; Hydroxamic Acids/*pharmacology ; Indoles/*pharmacology ; Lateral Ventricles/pathology ; Male ; Mice, Transgenic ; Mutation ; Neurons/*drug effects/metabolism/physiology ; Panobinostat ; Rats ; }, abstract = {Huntington disease (HD) is an autosomal dominant neurodegenerative disorder caused by expanded CAG repeats in the huntingtin gene (HTT). Although mutant HTT is expressed during embryonic development and throughout life, clinical HD usually manifests later in adulthood. A number of studies document neurodevelopmental changes associated with mutant HTT, but whether these are reversible under therapy remains unclear. Here, we identify very early behavioral, molecular, and cellular changes in preweaning transgenic HD rats and mice. Reduced ultrasonic vocalization, loss of prepulse inhibition, and increased risk taking are accompanied by disturbances of dopaminergic regulation in vivo, reduced neuronal differentiation capacity in subventricular zone stem/progenitor cells, and impaired neuronal and oligodendrocyte differentiation of mouse embryo-derived neural stem cells in vitro. Interventional treatment of this early phenotype with the histone deacetylase inhibitor (HDACi) LBH589 led to significant improvement in behavioral changes and markers of dopaminergic neurotransmission and complete reversal of aberrant neuronal differentiation in vitro and in vivo. Our data support the notion that neurodevelopmental changes contribute to the prodromal phase of HD and that early, presymptomatic intervention using HDACi may represent a promising novel treatment approach for HD.}, } @article {pmid30150377, year = {2018}, author = {González-Guarda, E and Petermann-Pichincura, A and Tornero, C and Domingo, L and Agustí, J and Pino, M and Abarzúa, AM and Capriles, JM and Villavicencio, NA and Labarca, R and Tolorza, V and Sevilla, P and Rivals, F}, title = {Multiproxy evidence for leaf-browsing and closed habitats in extinct proboscideans (Mammalia, Proboscidea) from Central Chile.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9258-9263}, pmid = {30150377}, issn = {1091-6490}, mesh = {Animals ; Chile ; *Ecosystem ; *Extinction, Biological ; *Fossils ; Proboscidea Mammal/*physiology ; }, abstract = {Proboscideans are so-called ecosystem engineers and are considered key players in hypotheses about Late Pleistocene megafaunal extinctions. However, knowledge about the autoecology and chronology of the proboscideans in South America is still open to debate and raises controversial views. Here, we used a range of multiproxy approaches and new radiocarbon datings to study the autoecology of Chilean gomphotheres, the only group of proboscideans to reach South America during the Great American Biotic Interchange (∼3.1 to 2.7 million years before present). As part of this study, we analyzed stable isotopes, dental microwear, and dental calculus microfossils on gomphothere molars from 30 Late Pleistocene sites (31° to 42°S). These proxies provided different scales of temporal resolution, which were then combined to assess the dietary and habitat patterns of these proboscideans. The multiproxy study suggests that most foraging took place in relatively closed environments. In Central Chile, there is a positive correlation between lower δ13C values and an increasing consumption of arboreal/scrub elements. Analyses of dental microwear and calculus microfossils have verified these leaf-browsing feeding habits. From a comparative perspective, the dietary pattern of South American gomphotheres appears to be constrained more by resource availability than by the potential dietary range of the individual taxa. This multiproxy study is aimed at increasing knowledge of the life history of gomphotheres and thus follows an issue considered one of the greatest challenges for paleontology in South America, recently pointed out by the need to thoroughly understand the role of ecological engineers before making predictions about the consequences of ecosystem defaunation.}, } @article {pmid30150376, year = {2018}, author = {Bloemraad, I}, title = {Understanding refugee naturalization as partnership.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9054-9056}, pmid = {30150376}, issn = {1091-6490}, mesh = {*Refugees ; }, } @article {pmid30150375, year = {2018}, author = {Kluber, A and Burt, TA and Clementi, C}, title = {Size and topology modulate the effects of frustration in protein folding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9234-9239}, pmid = {30150375}, issn = {1091-6490}, mesh = {*Models, Chemical ; *Protein Folding ; Protein Structure, Secondary ; Proteins/*chemistry ; }, abstract = {The presence of conflicting interactions, or frustration, determines how fast biomolecules can explore their configurational landscapes. Recent experiments have provided cases of systems with slow reconfiguration dynamics, perhaps arising from frustration. While it is well known that protein folding speed and mechanism are strongly affected by the protein native structure, it is still unknown how the response to frustration is modulated by the protein topology. We explore the effects of nonnative interactions in the reconfigurational and folding dynamics of proteins with different sizes and topologies. We find that structural correlations related to the folded state size and topology play an important role in determining the folding kinetics of proteins that otherwise have the same amount of nonnative interactions. In particular, we find that the reconfiguration dynamics of α-helical proteins are more susceptible to frustration than β-sheet proteins of the same size. Our results may explain recent experimental findings and suggest that attempts to measure the degree of frustration due to nonnative interactions might be more successful with α-helical proteins.}, } @article {pmid30150374, year = {2018}, author = {Wang, Y and Su, L and Morin, MD and Jones, BT and Mifune, Y and Shi, H and Wang, KW and Zhan, X and Liu, A and Wang, J and Li, X and Tang, M and Ludwig, S and Hildebrand, S and Zhou, K and Siegwart, DJ and Moresco, EMY and Zhang, H and Boger, DL and Beutler, B}, title = {Adjuvant effect of the novel TLR1/TLR2 agonist Diprovocim synergizes with anti-PD-L1 to eliminate melanoma in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8698-E8706}, pmid = {30150374}, issn = {1091-6490}, support = {R01 AI125581/AI/NIAID NIH HHS/United States ; R01 CA042056/CA/NCI NIH HHS/United States ; U24 AI082657/AI/NIAID NIH HHS/United States ; }, mesh = {Adjuvants, Immunologic/*pharmacology ; Animals ; Antibodies, Monoclonal/immunology/*pharmacology ; B7-H1 Antigen/*antagonists & inhibitors/immunology ; Cell Line, Tumor ; Cells, Cultured ; Drug Synergism ; Humans ; Immunotherapy/methods ; Kaplan-Meier Estimate ; Melanoma, Experimental/genetics/immunology/*therapy ; Mice, Inbred C57BL ; Mice, Knockout ; Ovalbumin/immunology ; THP-1 Cells ; Toll-Like Receptor 1/*agonists/genetics/metabolism ; Toll-Like Receptor 2/*agonists/genetics/metabolism ; }, abstract = {Successful cancer immunotherapy entails activation of innate immune receptors to promote dendritic cell (DC) maturation, antigen presentation, up-regulation of costimulatory molecules, and cytokine secretion, leading to activation of tumor antigen-specific cytotoxic T lymphocytes (CTLs). Here we screened a synthetic library of 100,000 compounds for innate immune activators using TNF production by THP-1 cells as a readout. We identified and optimized a potent human and mouse Toll-like receptor (TLR)1/TLR2 agonist, Diprovocim, which exhibited an EC50 of 110 pM in human THP-1 cells and 1.3 nM in primary mouse peritoneal macrophages. In mice, Diprovocim-adjuvanted ovalbumin immunization promoted antigen-specific humoral and CTL responses and synergized with anti-PD-L1 treatment to inhibit tumor growth, generating long-term antitumor memory, curing or prolonging survival of mice engrafted with the murine melanoma B16-OVA. Diprovocim induced greater frequencies of tumor-infiltrating leukocytes than alum, of which CD8 T cells were necessary for the antitumor effect of immunization plus anti-PD-L1 treatment.}, } @article {pmid30150373, year = {2018}, author = {Mitropoulou, AN and Bowen, H and Dodev, TS and Davies, AM and Bax, HJ and Beavil, RL and Beavil, AJ and Gould, HJ and James, LK and Sutton, BJ}, title = {Structure of a patient-derived antibody in complex with allergen reveals simultaneous conventional and superantigen-like recognition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8707-E8716}, pmid = {30150373}, issn = {1091-6490}, support = {G1100090//Medical Research Council/United Kingdom ; G1000758//Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {Antibodies, Monoclonal/chemistry/*immunology/metabolism ; Antibody Specificity/immunology ; Antigens, Plant/chemistry/*immunology/metabolism ; Basophils/immunology/physiology ; Calcium-Binding Proteins/chemistry/*immunology/metabolism ; Cell Degranulation/immunology ; Cross Reactions/immunology ; Crystallography, X-Ray ; Epitopes/chemistry/*immunology/metabolism ; Humans ; Immunoglobulin E/chemistry/immunology/metabolism ; Models, Molecular ; Protein Binding ; Protein Conformation ; Superantigens/chemistry/*immunology/metabolism ; }, abstract = {Antibodies classically bind antigens via their complementarity-determining regions, but an alternative mode of interaction involving V-domain framework regions has been observed for some B cell "superantigens." We report the crystal structure of an antibody employing both modes of interaction simultaneously and binding two antigen molecules. This human antibody from an allergic individual binds to the grass pollen allergen Phl p 7. Not only are two allergen molecules bound to each antibody fragment (Fab) but also each allergen molecule is bound by two Fabs: One epitope is recognized classically, the other in a superantigen-like manner. A single allergen molecule thus cross-links two identical Fabs, contrary to the one-antibody-one-epitope dogma, which dictates that a dimeric allergen at least is required for this to occur. Allergens trigger immediate hypersensitivity reactions by cross-linking receptor-bound IgE molecules on effector cells. We found that monomeric Phl p 7 induced degranulation of basophils sensitized solely with this monoclonal antibody expressed as an IgE, demonstrating that the dual specificity has functional consequences. The monomeric state of Phl p 7 and two structurally related allergens was confirmed by size-exclusion chromatography and multiangle laser light scattering, and the results were supported by degranulation studies with the related allergens, a second patient-derived allergen-specific antibody lacking the nonclassical binding site, and mutagenesis of the nonclassically recognized allergen epitope. The antibody dual reactivity and cross-linking mechanism not only have implications for understanding allergenicity and allergen potency but, importantly, also have broader relevance to antigen recognition by membrane Ig and cross-linking of the B cell receptor.}, } @article {pmid30150372, year = {2018}, author = {Carr, JA and Aellen, M and Franke, D and So, PTC and Bruns, OT and Bawendi, MG}, title = {Absorption by water increases fluorescence image contrast of biological tissue in the shortwave infrared.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9080-9085}, pmid = {30150372}, issn = {1091-6490}, support = {P41 EB015871/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; *Infrared Rays ; Mice ; *Models, Theoretical ; Optical Imaging/instrumentation/*methods ; Water/*chemistry ; }, abstract = {Recent technology developments have expanded the wavelength window for biological fluorescence imaging into the shortwave infrared. We show here a mechanistic understanding of how drastic changes in fluorescence imaging contrast can arise from slight changes of imaging wavelength in the shortwave infrared. We demonstrate, in 3D tissue phantoms and in vivo in mice, that light absorption by water within biological tissue increases image contrast due to attenuation of background and highly scattered light. Wavelengths of strong tissue absorption have conventionally been avoided in fluorescence imaging to maximize photon penetration depth and photon collection, yet we demonstrate that imaging at the peak absorbance of water (near 1,450 nm) results in the highest image contrast in the shortwave infrared. Furthermore, we show, through microscopy of highly labeled ex vivo biological tissue, that the contrast improvement from water absorption enables resolution of deeper structures, resulting in a higher imaging penetration depth. We then illustrate these findings in a theoretical model. Our results suggest that the wavelength-dependent absorptivity of water is the dominant optical property contributing to image contrast, and is therefore crucial for determining the optimal imaging window in the infrared.}, } @article {pmid30150371, year = {2018}, author = {Goodwell, AE and Kumar, P and Fellows, AW and Flerchinger, GN}, title = {Dynamic process connectivity explains ecohydrologic responses to rainfall pulses and drought.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8604-E8613}, pmid = {30150371}, issn = {1091-6490}, abstract = {Ecohydrologic fluxes within atmosphere, vegetation, and soil systems exhibit a joint variability that arises from forcing and feedback interactions. These interactions cause fluctuations to propagate between variables at many time scales. In an ecosystem, this connectivity dictates responses to climate change, land-cover change, and weather events and must be characterized to understand resilience and sensitivity. We use an information theory-based approach to quantify connectivity in the form of information flow associated with the propagation of fluctuations between variables. We apply this approach to study ecosystems that experience changes in dry-season moisture availability due to rainfall and drought conditions. We use data from two transects with flux towers located along elevation gradients and quantify redundant, synergistic, and unique flow of information between lagged sources and targets to characterize joint asynchronous time dependencies. At the Reynolds Creek Critical Zone Observatory in Idaho, a dry-season rainfall pulse leads to increased connectivity from soil and atmospheric variables to heat and carbon fluxes. At the Southern Sierra Critical Zone Observatory in California, separate sets of dominant drivers characterize two sites at which fluxes exhibit different drought responses. For both cases, our information flow-based connectivity characterizes dominant drivers and joint variability before, during, and after disturbances. This approach to gauge the responsiveness of ecosystem fluxes under multiple sources of variability furthers our understanding of complex ecohydrologic systems.}, } @article {pmid30150370, year = {2018}, author = {Fujimoto, M and Sazuka, T and Oda, Y and Kawahigashi, H and Wu, J and Takanashi, H and Ohnishi, T and Yoneda, JI and Ishimori, M and Kajiya-Kanegae, H and Hibara, KI and Ishizuna, F and Ebine, K and Ueda, T and Tokunaga, T and Iwata, H and Matsumoto, T and Kasuga, S and Yonemaru, JI and Tsutsumi, N}, title = {Transcriptional switch for programmed cell death in pith parenchyma of sorghum stems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8783-E8792}, pmid = {30150370}, issn = {1091-6490}, mesh = {Apoptosis/*genetics ; Arabidopsis/cytology/genetics/metabolism ; Base Sequence ; Carbohydrates/analysis ; Chromosome Mapping ; Chromosomes, Plant/genetics ; *Gene Expression Regulation, Plant ; Geography ; Phylogeny ; Plant Proteins/classification/*genetics/metabolism ; Plant Stems/cytology/*genetics/metabolism ; Sequence Homology, Nucleic Acid ; Sorghum/cytology/*genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {Pith parenchyma cells store water in various plant organs. These cells are especially important for producing sugar and ethanol from the sugar juice of grass stems. In many plants, the death of pith parenchyma cells reduces their stem water content. Previous studies proposed that a hypothetical D gene might be responsible for the death of stem pith parenchyma cells in Sorghum bicolor, a promising energy grass, although its identity and molecular function are unknown. Here, we identify the D gene and note that it is located on chromosome 6 in agreement with previous predictions. Sorghum varieties with a functional D allele had stems enriched with dry, dead pith parenchyma cells, whereas those with each of six independent nonfunctional D alleles had stems enriched with juicy, living pith parenchyma cells. D expression was spatiotemporally coupled with the appearance of dead, air-filled pith parenchyma cells in sorghum stems. Among D homologs that are present in flowering plants, Arabidopsis ANAC074 also is required for the death of stem pith parenchyma cells. D and ANAC074 encode previously uncharacterized NAC transcription factors and are sufficient to ectopically induce programmed death of Arabidopsis culture cells via the activation of autolytic enzymes. Taken together, these results indicate that D and its Arabidopsis ortholog, ANAC074, are master transcriptional switches that induce programmed death of stem pith parenchyma cells. Thus, targeting the D gene will provide an approach to breeding crops for sugar and ethanol production.}, } @article {pmid30150369, year = {2018}, author = {Servili, E and Trus, M and Maayan, D and Atlas, D}, title = {β-Subunit of the voltage-gated Ca2+ channel Cav1.2 drives signaling to the nucleus via H-Ras.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8624-E8633}, pmid = {30150369}, issn = {1091-6490}, mesh = {Calcium/metabolism ; Calcium Channels, L-Type/genetics/*metabolism ; Cell Line, Tumor ; Cell Nucleus/metabolism ; HEK293 Cells ; Humans ; Methyl-CpG-Binding Protein 2/genetics/metabolism ; Mutation ; Neurons/metabolism ; Protein Binding ; Protein Subunits/genetics/metabolism ; Proto-Oncogene Proteins c-fos/genetics/metabolism ; Proto-Oncogene Proteins p21(ras)/*metabolism ; *Signal Transduction ; }, abstract = {Depolarization-induced signaling to the nucleus by the L-type voltage-gated calcium channel Cav1.2 is widely assumed to proceed by elevating intracellular calcium. The apparent lack of quantitative correlation between Ca2+ influx and gene activation suggests an alternative activation pathway. Here, we demonstrate that membrane depolarization of HEK293 cells transfected with α11.2/β2b/α2δ subunits (Cav1.2) triggers c-Fos and MeCP2 activation via the Ras/ERK/CREB pathway. Nuclear signaling is lost either by absence of the intracellular β2 subunit or by transfecting the cells with the channel mutant α11.2W440A/β2b/α2δ, a mutation that disrupts the interaction between α11.2 and β2 subunits. Pulldown assays in neuronal SH-SY5Y cells and in vitro binding of recombinant H-Ras and β2 confirmed the importance of the intracellular β2 subunit for depolarization-induced gene activation. Using a Ca2+-impermeable mutant channel α11.2L745P/β2b/α2δ or disrupting Ca2+/calmodulin binding to the channel using the channel mutant α11.2I1624A/β2b/α2δ, we demonstrate that depolarization-induced c-Fos and MeCP2 activation does not depend on Ca2+ transport by the channel. Thus, in contrast to the paradigm that elevated intracellular Ca2+ drives nuclear signaling, we show that Cav1.2-triggered c-Fos or MeCP2 is dependent on extracellular Ca2+ and Ca2+ occupancy of the open channel pore, but is Ca2+-influx independent. An indispensable β-subunit interaction with H-Ras, which is triggered by conformational changes at α11.2 independently of Ca2+ flux, brings to light a master regulatory role of β2 in transcriptional activation via the ERK/CREB pathway. This mode of H-Ras activation could have broad implications for understanding the coupling of membrane depolarization to the rapid induction of gene transcription.}, } @article {pmid30150229, year = {2018}, author = {Watson, CFI and Matsuzawa, T}, title = {Correction to 'Behaviour of nonhuman primate mothers toward their dead infants: uncovering mechanisms'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, doi = {10.1098/rstb.2018.0381}, pmid = {30150229}, issn = {1471-2970}, } @article {pmid30150228, year = {2018}, author = {Hall, MD and Mideo, N}, title = {Linking sex differences to the evolution of infectious disease life-histories.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150228}, issn = {1471-2970}, abstract = {Sex differences in the prevalence, course and severity of infection are widespread, yet the evolutionary consequences of these differences remain unclear. Understanding how male-female differences affect the trajectory of infectious disease requires connecting the contrasting dynamics that pathogens might experience within each sex to the number of susceptible and infected individuals that are circulating in a population. In this study, we build on theory using genetic covariance functions to link the growth of a pathogen within a host to the evolution and spread of disease between individuals. Using the Daphnia-Pasteuria system as a test case, we show that on the basis of within-host dynamics alone, females seem to be more evolutionarily liable for the pathogen, with higher spore loads and greater divergence among pathogen genotypes as infection progresses. Between-host transmission, however, appears to offset the lower performance of a pathogen within a male host, making even subtle differences between the sexes evolutionarily relevant, as long as the selection generated by the between-host dynamics is sufficiently strong. Our model suggests that relatively simple differences in within-host processes occurring in males and females can lead to complex patterns of genetic constraint on pathogen evolution, particularly during an expanding epidemic.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150227, year = {2018}, author = {Forsman, A}, title = {On the role of sex differences for evolution in heterogeneous and changing fitness landscapes: insights from pygmy grasshoppers.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150227}, issn = {1471-2970}, abstract = {Much research has been devoted to study evolution of local adaptations by natural selection, and to explore the roles of neutral processes and developmental plasticity for patterns of diversity among individuals, populations and species. Some aspects, such as evolution of adaptive variation in phenotypic traits in stable environments, and the role of plasticity in predictable changing environments, are well understood. Other aspects, such as the role of sex differences for evolution in spatially heterogeneous and temporally changing environments and dynamic fitness landscapes, remain elusive. An increased understanding of evolution requires that sex differences in development, physiology, morphology, life-history and behaviours are more broadly considered. Studies of selection should take into consideration that the relationships linking phenotypes to fitness may vary not only according to environmental conditions but also differ between males and females. Such opposing selection, sex-by-environment interaction effects of selection and sex-specific developmental plasticity can have consequences for population differentiation, local adaptations and for the dynamics of polymorphisms. Integrating sex differences in analytical frameworks and population comparisons can therefore illuminate neglected evolutionary drivers and reconcile unexpected patterns. Here, I illustrate these issues using empirical examples from over 20 years of research on colour polymorphic Tetrix subulata and Tetrix undulata pygmy grasshoppers, and summarize findings from observational field studies, manipulation experiments, common garden breeding experiments and population genetics studies.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150226, year = {2018}, author = {Mishra, A and Tung, S and Shreenidhi, PM and Aamir Sadiq, M and Shree Sruti, VR and Chakraborty, PP and Dey, S}, title = {Sex differences in dispersal syndrome are modulated by environment and evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150226}, issn = {1471-2970}, abstract = {Dispersal syndromes (i.e. suites of phenotypic correlates of dispersal) are potentially important determinants of local adaptation in populations. Species that exhibit sexual dimorphism in their life history or behaviour may exhibit sex-specific differences in their dispersal syndromes. Unfortunately, there is little empirical evidence of sex differences in dispersal syndromes and how they respond to environmental change or dispersal evolution. We investigated these issues using two same-generation studies and a long-term (greater than 70 generations) selection experiment on laboratory populations of Drosophila melanogaster There was a marked difference between the dispersal syndromes of males and females, the extent of which was modulated by nutrition availability. Moreover, dispersal evolution via spatial sorting reversed the direction of dispersal×sex interaction in one trait (desiccation resistance), while eliminating the sex difference in another trait (body size). Thus, we show that sex differences obtained through same-generation trait-associations ('ecological dispersal syndromes') are probably environment-dependent. Moreover, even under constant environments, they are not good predictors of the sex differences in 'evolutionary dispersal syndrome' (i.e. trait-associations shaped during dispersal evolution). Our findings have implications for local adaptation in the context of sex-biased dispersal and habitat-matching, as well as for the use of dispersal syndromes as a proxy of dispersal.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150225, year = {2018}, author = {Allen, SL and Bonduriansky, R and Chenoweth, SF}, title = {Genetic constraints on microevolutionary divergence of sex-biased gene expression.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150225}, issn = {1471-2970}, abstract = {The evolution of sex-specific phenotypes is an important dimension of diversification and local adaptation. The sex-dependent regulation of gene expression is considered a key genomic mechanism facilitating sex-dependent adaptation. In many species, genes with male-biased expression evolve faster in DNA sequence and expression level than genes with female-biased or sexually monomorphic expression. While positive selection may be responsible for rapid DNA sequence evolution, why expression of male-biased genes also evolves rapidly remains unclear. Beyond sex differences in selection, some aspects of the genetic architecture of gene expression could contribute to the rapid evolution of male-biased gene expression. First, male-biased genes might simply have greater standing genetic variance than female-biased genes. Second, male-biased genes could be less constrained by pleiotropy, either within or between sexes. Here, we evaluate these alternative explanations on an intraspecific scale using a series of quantitative genetic experiments conducted on natural variation in male and female gene expression in the fly Drosophila serrata Male-biased genes had significantly higher genetic variance than female-biased genes and were generally more narrowly expressed across tissues, suggesting lower within-individual pleiotropy. However, consistent with stronger constraints due to between-sex pleiotropy, their between-sex genetic correlations, rMF, were higher than for female-biased genes and more strongly negatively associated with sex bias. Using an extensive clinal dataset, we tested whether sex differences in gene expression divergence among populations have been shaped by pleiotropy. Here too, male-biased gene divergence was more strongly associated with between-sex pleiotropy than was female-biased gene divergence. Systematic differences in genetic variance and pleiotropy may be important factors influencing sex-specific adaptation arising through changes in gene expression.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150224, year = {2018}, author = {Olito, C and Abbott, JK and Jordan, CY}, title = {The interaction between sex-specific selection and local adaptation in species without separate sexes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150224}, issn = {1471-2970}, abstract = {Local adaptation in hermaphrodite species can be based on a variety of fitness components, including survival, as well as both female and male sex-functions within individuals. When selection via female and male fitness components varies spatially (e.g. due to environmental heterogeneity), local adaptation will depend, in part, on variation in selection through each fitness component, and the extent to which genetic trade-offs between sex-functions maintain genetic variation necessary for adaptation. Local adaptation will also depend on the hermaphrodite mating system because self-fertilization alters several key factors influencing selection and the maintenance of genetic variance underlying trade-offs between the sex-functions (sexually antagonistic polymorphism). As a first step to guide intuition regarding sex-specific adaptation in hermaphrodites, we develop a simple theoretical model incorporating the essential features of hermaphrodite mating and adaptation in a spatially heterogeneous environment, and explore the interaction between sex-specific selection, self-fertilization and local adaptation. Our results suggest that opportunities for sex-specific local adaptation in hermaphrodites depend strongly on the extent of self-fertilization and inbreeding depression. Using our model as a conceptual framework, we provide a broad overview of the literature on sex-specific selection and local adaptation in hermaphroditic plants and animals, emphasizing promising future directions in light of our theoretical predictions.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150223, year = {2018}, author = {Li, XY and Holman, L}, title = {Evolution of female choice under intralocus sexual conflict and genotype-by-environment interactions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150223}, issn = {1471-2970}, abstract = {In many species, females are hypothesized to obtain 'good genes' for their offspring by mating with males in good condition. However, female preferences might deplete genetic variance and make choice redundant. Additionally, high-condition males sometimes produce low-fitness offspring, for example because of environmental turnover and gene-by-environment interactions (GEIs) for fitness, or because fit males carry sexually antagonistic alleles causing them to produce unfit daughters. Here, we extend previous theory by investigating the evolution of female mate choice in a spatially explicit evolutionary simulation implementing both GEIs and intralocus sexual conflict (IASC), under sex-specific hard or soft selection. We show that IASC can weaken female preferences for high-condition males or even cause a preference for males in low condition, depending on the relative benefits of producing well-adapted sons versus daughters, which in turn depends on the relative hardness of selection on males and females. We discuss the relevance of our results to conservation genetics and empirical evolutionary biology.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150222, year = {2018}, author = {Gerber, N and Kokko, H}, title = {Abandoning the ship using sex, dispersal or dormancy: multiple escape routes from challenging conditions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150222}, issn = {1471-2970}, abstract = {Natural populations often experience environments that vary across space and over time, leading to spatio-temporal variation of the fitness of a genotype. If local conditions are poor, organisms can disperse in space (physical movement) or time (dormancy, diapause). Facultatively sexual organisms can switch between asexual and sexual reproduction, and thus have a third option available to deal with maladaptedness: they can engage in sexual reproduction in unfavourable conditions (an 'abandon-ship' response). Sexual reproduction in facultatively sexual organisms is often coupled with dispersal and/or dormancy, while bet-hedging theory at first sight predicts sex, dispersal and dormancy to covary negatively, as they represent different escape mechanisms that could substitute for each other. Here we briefly review the observed links between sex, dormancy and dispersal, and model the expected covariation patterns of dispersal, dormancy and the reproductive mode in the context of local adaptation to spatio-temporally fluctuating environments. The correlations between sex, dormancy and dispersal evolve differently within species versus across species. Various risk-spreading strategies are not completely interchangeable, as each has dynamic consequences that can feed back into the profitability of others. Our results shed light on the discrepancy between previous theoretical predictions on covarying risk-spreading traits and help explain why sex often associates with other means of escaping unfavourable situations.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150221, year = {2018}, author = {Connallon, T and Olito, C and Dutoit, L and Papoli, H and Ruzicka, F and Yong, L}, title = {Local adaptation and the evolution of inversions on sex chromosomes and autosomes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150221}, issn = {1471-2970}, abstract = {Spatially varying selection with gene flow can favour the evolution of inversions that bind locally adapted alleles together, facilitate local adaptation and ultimately drive genomic divergence between species. Several studies have shown that the rates of spread and establishment of new inversions capturing locally adaptive alleles depend on a suite of evolutionary factors, including the strength of selection for local adaptation, rates of gene flow and recombination, and the deleterious mutation load carried by inversions. Because the balance of these factors is expected to differ between X (or Z) chromosomes and autosomes, opportunities for inversion evolution are likely to systematically differ between these genomic regions, though such scenarios have not been formally modelled. Here, we consider the evolutionary dynamics of X-linked and autosomal inversions in populations evolving at a balance between migration and local selection. We identify three factors that lead to asymmetric rates of X-linked and autosome inversion establishment: (1) sex-biased migration, (2) dominance of locally adapted alleles and (3) chromosome-specific deleterious mutation loads. This theory predicts an elevated rate of fixation, and depressed opportunities for polymorphism, for X-linked inversions. Our survey of data on the genomic distribution of polymorphic and fixed inversions supports both theoretical predictions.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150220, year = {2018}, author = {Burke, NW and Bonduriansky, R}, title = {The geography of sex: sexual conflict, environmental gradients and local loss of sex in facultatively parthenogenetic animals.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150220}, issn = {1471-2970}, abstract = {Obligately asexual organisms tend to occur at higher altitudes or latitudes and occupy larger ranges than their obligately sexual relatives-a phenomenon called geographical parthenogenesis. Some facultatively parthenogenetic organisms that reproduce both sexually and asexually also exhibit spatial variation in reproductive mode. Theory suggests that sexual conflict and mate limitation can determine the relative frequency of sex in facultative parthenogens, but the effect of these dynamics on spatial distributions is unknown. Here, we use individual-based models to investigate whether these dynamics can generate local differences in the reproductive mode in a facultatively parthenogenetic metapopulation occupying an environmental gradient. We find that selection for resistance and high fecundity creates positive epistasis in virgin females between a mutant allele for parthenogenesis and alleles for resistance, resulting in female-biased sex ratios and higher resistance and coercion towards the productive 'core' of the metapopulation. However, steeper environmental gradients, which lead to lower density and less mating at the 'edge', generate female bias without promoting coercion or resistance. Our analysis shows that local adaptation of facultatively parthenogenetic populations subject to sexual conflict and productivity gradients can generate striking spatial variation suggesting new patterns for empirical investigation. These findings could also help to explain the rarity of facultative parthenogenesis in animals.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150219, year = {2018}, author = {Svensson, EI and Goedert, D and Gómez-Llano, MA and Spagopoulou, F and Nava-Bolaños, A and Booksmythe, I}, title = {Sex differences in local adaptation: what can we learn from reciprocal transplant experiments?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150219}, issn = {1471-2970}, abstract = {Local adaptation is of fundamental interest to evolutionary biologists. Traditionally, local adaptation has been studied using reciprocal transplant experiments to quantify fitness differences between residents and immigrants in pairwise transplants between study populations. Previous studies have detected local adaptation in some cases, but others have shown lack of adaptation or even maladaptation. Recently, the importance of different fitness components, such as survival and fecundity, to local adaptation have been emphasized. Here, we address another neglected aspect in studies of local adaptation: sex differences. Given the ubiquity of sexual dimorphism in life histories and phenotypic traits, this neglect is surprising, but may be partly explained by differences in research traditions and terminology in the fields of local adaptation and sexual selection. Studies that investigate differences in mating success between resident and immigrants across populations tend to be framed in terms of reproductive and behavioural isolation, rather than local adaptation. We briefly review the published literature that bridges these areas and suggest that reciprocal transplant experiments could benefit from quantifying both male and female fitness components. Such a more integrative research approach could clarify the role of sex differences in the evolution of local adaptations.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150218, year = {2018}, author = {Runemark, A and Eroukhmanoff, F and Nava-Bolaños, A and Hermansen, JS and Meier, JI}, title = {Hybridization, sex-specific genomic architecture and local adaptation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150218}, issn = {1471-2970}, abstract = {While gene flow can reduce the potential for local adaptation, hybridization may conversely provide genetic variation that increases the potential for local adaptation. Hybridization may also affect adaptation through altering sexual dimorphism and sexual conflict, but this remains largely unstudied. Here, we discuss how hybridization may affect sexual dimorphism and conflict due to differential effects of hybridization on males and females, and then how this, in turn, may affect local adaptation. First, in species with heterochromatic sexes, the lower viability of the heterogametic sex in hybrids could shift the balance in sexual conflict. Second, sex-specific inheritance of the mitochondrial genome in hybrids may lead to cytonuclear mismatches, for example, in the form of 'mother's curse', with potential consequences for sex ratio and sex-specific expression. Third, sex-biased introgression and recombination may lead to sex-specific consequences of hybridization. Fourth, transgressive segregation of sexually antagonistic alleles could increase sexual dimorphism in hybrid populations. Sexual dimorphism can reduce sexual conflict and enhance intersexual niche partitioning, increasing the fitness of hybrids. Adaptive introgression of alleles reducing sexual conflict or enhancing intersexual niche partitioning may facilitate local adaptation, and could favour the colonization of novel habitats. We review these consequences of hybridization on sex differences and local adaptation, and discuss how their prevalence and importance could be tested empirically.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150217, year = {2018}, author = {Perry, JC and Rowe, L}, title = {Sexual conflict in its ecological setting.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150217}, issn = {1471-2970}, abstract = {Sexual conflict can lead to rapid and continuous coevolution between females and males, without any inputs from varying ecology. Yet both the degree of conflict and selection on antagonistic traits are known to be sensitive to local ecological conditions. This leads to the longstanding question: to what extent does variation in ecological context drive sexually antagonistic coevolution? In water striders, there is much information about the impacts of ecological factors on conflict, and about patterns of antagonistic coevolution. However, the connection between the two is poorly understood. Here, we first review the multiple ways in which ecological context might affect the coevolutionary trajectory of the sexes. We then review ecological and coevolutionary patterns in water striders, and connections between them, in light of theory and new data. Our analysis suggests that ecological variation does impact observed patterns of antagonistic coevolution, but highlights significant uncertainty due to the multiple pathways by which ecological factors can influence conflict and its evolutionary outcome. To the extent that water striders are a reasonable reflection of other systems, this observation serves as both an opportunity and a warning: there is much to learn, but gaining insight may be a daunting process in many systems.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150216, year = {2018}, author = {De Lisle, SP and Goedert, D and Reedy, AM and Svensson, EI}, title = {Climatic factors and species range position predict sexually antagonistic selection across taxa.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150216}, issn = {1471-2970}, abstract = {Sex differences in selection are ubiquitous in sexually reproducing organisms. When the genetic basis of traits is shared between the sexes, such sexually antagonistic selection (SAS) creates a potential constraint on adaptive evolution. Theory and laboratory experiments suggest that environmental variation and the degree of local adaptation may all affect the frequency and intensity of SAS. Here, we capitalize on a large database of over 700 spatially or temporally replicated estimates of sex-specific phenotypic selection from wild populations, combined with data on microclimates and geographical range information. We performed a meta-analysis to test three predictions from SAS theory, that selection becomes more concordant between males and females: (1) in more stressful environments, (2) in more variable environments and (3) closer to the edge of the species' range. We find partial empirical support for all three predictions. Within-study analyses indicate SAS decreases in extreme environments, as indicated by a relationship with maximum temperature, minimum precipitation and evaporative potential (PET). Across studies, we found that the average level of SAS at high latitudes was lower, where environmental conditions are typically less stable. Finally, we found evidence for reduced SAS in populations that are far from the centre of their geographical range. However, and notably, we also found some evidence of reduced average strength of selection in these populations, which is in contrast to predictions from classical theoretical models on range limit evolution. Our results suggest that environmental lability and species range position predictably influence sex-specific selection and sexual antagonism in the wild.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150215, year = {2018}, author = {Connallon, T and Débarre, F and Li, XY}, title = {Linking local adaptation with the evolution of sex differences.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1757}, pages = {}, pmid = {30150215}, issn = {1471-2970}, abstract = {Many conspicuous forms of evolutionary diversity occur within species. Two prominent examples include evolutionary divergence between populations differentially adapted to their local environments (local adaptation), and divergence between females and males in response to sex differences in selection (sexual dimorphism sensu lato). These two forms of diversity have inspired vibrant research programmes, yet these fields have largely developed in isolation from one another. Nevertheless, conceptual parallels between these research traditions are striking. Opportunities for local adaptation strike a balance between local selection, which promotes divergence, and gene flow-via dispersal and interbreeding between populations-which constrains it. Sex differences are similarly constrained by fundamental features of inheritance that mimic gene flow. Offspring of each sex inherit genes from same-sex and opposite-sex parents, leading to gene flow between each differentially selected half of the population, and raising the question of how sex differences arise and are maintained. This special issue synthesizes and extends emerging research at the interface between the research traditions of local adaptation and sex differences. Each field can promote understanding of the other, and interactions between local adaptation and sex differences can generate new empirical predictions about the evolutionary consequences of selection that varies across space, time, and between the sexes.This article is part of the theme issue 'Linking local adaptation with the evolution of sex differences'.}, } @article {pmid30150002, year = {2018}, author = {Anderson, TJC and LoVerde, PT and Le Clec'h, W and Chevalier, FD}, title = {Genetic Crosses and Linkage Mapping in Schistosome Parasites.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {982-996}, doi = {10.1016/j.pt.2018.08.001}, pmid = {30150002}, issn = {1471-5007}, support = {R01 AI097576/AI/NIAID NIH HHS/United States ; R01 AI133749/AI/NIAID NIH HHS/United States ; R21 AI072704/AI/NIAID NIH HHS/United States ; R01 AI115691/AI/NIAID NIH HHS/United States ; R21 AI096277/AI/NIAID NIH HHS/United States ; R01 AI123434/AI/NIAID NIH HHS/United States ; }, abstract = {Linkage mapping - utilizing experimental genetic crosses to examine cosegregation of phenotypic traits with genetic markers - is now 100 years old. Schistosome parasites are exquisitely well suited to linkage mapping approaches because genetic crosses can be conducted in the laboratory, thousands of progeny are produced, and elegant experimental work over the last 75 years has revealed heritable genetic variation in multiple biomedically important traits such as drug resistance, host specificity, and virulence. Application of this approach is timely because the improved genome assembly for Schistosoma mansoni and developing molecular toolkit for schistosomes increase our ability to link phenotype with genotype. We describe current progress and potential future directions of linkage mapping in schistosomes.}, } @article {pmid30149995, year = {2018}, author = {Atwater, AL and Kirk, EC}, title = {New middle Eocene omomyines (Primates, Haplorhini) from San Diego County, California.}, journal = {Journal of human evolution}, volume = {124}, number = {}, pages = {7-24}, doi = {10.1016/j.jhevol.2018.04.010}, pmid = {30149995}, issn = {1095-8606}, abstract = {The Friars Formation of San Diego County, California, has yielded a middle Eocene mammalian fauna from the early part of the Uintan North American Land Mammal Age. Prior research on the primate fauna from the Friars Formation provides evidence of one notharctine and multiple omomyine species, but many specimens collected since the early 1980s remain unstudied. Here we describe three new omomyine genera from the Friars Formation. These new taxa range in estimated body mass from about 119 g to 757 g, and substantially expand the diversity of middle Eocene omomyoids known from Southern California. Resolution of the phylogenetic relationships of the new Friars Formation omomyines is complicated by the fact that different character-taxon matrices and tree building methods produce different results. Nevertheless, all preliminary phylogenetic analyses are congruent in recovering a close relationship between the three new genera and the omomyines Macrotarsius, Omomys, Ourayia, and Utahia. Prior research has documented a shift in omomyoid diversity in North America from the anantomophine-rich Bridgerian to the omomyine-rich Uintan. Our description of three new Uintan omomyine taxa from the Friars Formation further emphasizes these opposite trends in anaptomorphine and omomyine species richness during the middle Eocene. All three of the new taxa are currently known from only the Friars Formation in San Diego County, California. Four of the previously known omomyoid genera from Southern California (Dyseolemur, Chumashius, Yaquius, and Stockia) are also endemic to the region, further highlighting the provincial character of primate faunas in Utah, Southern California, and West Texas during the Uintan.}, } @article {pmid30149911, year = {2018}, author = {Westoby, M and Kunstler, G and Leishman, MR and Morgan, J}, title = {How Species Boundaries Are Determined: A Response to Alexander et al.: (Trends in Ecology & Evolution 32, 7-8, 2017).}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {713}, doi = {10.1016/j.tree.2018.04.007}, pmid = {30149911}, issn = {1872-8383}, } @article {pmid30149801, year = {2018}, author = {Bascuñán, P and Niño-Garcia, JP and Galeano-Castañeda, Y and Serre, D and Correa, MM}, title = {Factors shaping the gut bacterial community assembly in two main Colombian malaria vectors.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {148}, pmid = {30149801}, issn = {2049-2618}, abstract = {BACKGROUND: The understanding of the roles of gut bacteria in the fitness and vectorial capacity of mosquitoes that transmit malaria, is improving; however, the factors shaping the composition and structure of such bacterial communities remain elusive. In this study, a high-throughput 16S rRNA gene sequencing was conducted to understand the effect of developmental stage, feeding status, species, and geography on the composition of the gut bacterial microbiota of two main Colombian malaria vectors, Anopheles nuneztovari and Anopheles darlingi.

RESULTS: The results revealed that mosquito developmental stage, followed by geographical location, are more important determinants of the gut bacterial composition than mosquito species or adult feeding status. Further, they showed that mosquito gut is a major filter for environmental bacteria colonization.

CONCLUSIONS: The sampling design and analytical approach of this study allowed to untangle the influence of factors that are simultaneously shaping the microbiota composition of two Latin-American malaria vectors, essential aspect for the design of vector biocontrol strategies.}, } @article {pmid30149053, year = {2018}, author = {Osborne, CD and Haritos, VS}, title = {Horizontal gene transfer of three co-inherited methane monooxygenase systems gave rise to methanotrophy in the Proteobacteria.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {171-181}, doi = {10.1016/j.ympev.2018.08.010}, pmid = {30149053}, issn = {1095-9513}, abstract = {The critical role that bacterial methanotrophs have in regulating the environmental concentrations of the potent greenhouse gas, methane, under aerobic conditions is dependent on monooxygenase enzymes which oxidise the substrate as both a carbon and energy source. Despite the importance of these organisms, the evolutionary origins of aerobic methane oxidation capability and its relationship to proteobacterial evolution is not well understood. Here we investigated the phylogenetic relationship of proteobacterial methanotrophs with related, non-methanotrophic bacteria using 16S rRNA and the evolution of two forms of methane monooxygenase: membrane bound (pMMO and pXMO) and cytoplasmic (sMMO). Through analysis we have concluded that extant proteobacterial methanotrophs evolved from up to five ancestral species, and that all three methane monooxygenase systems, pMMO, pXMO and sMMO, were likely present in the ancestral species (although pXMO and sMMO are not present in most of the present day methanotrophs). Here we propose that the three monooxygenase systems entered the ancestral species by horizontal gene transfer, with these likely to have pre-existing physiological and metabolic attributes that supported conversion to methanotrophy. Further, we suggest that prior to these enzyme systems developing methane oxidation capabilities, the membrane-bound and cytoplasmic monooxygenases were already both functionally and phylogenetically associated. These results not only suggest that sMMO and pXMO have a far greater role in methanotrophic evolution than previously understood but also implies that the co-inheritance of membrane bound and cytoplasmic monooxygenases have roles additional to that of supporting methanotrophy.}, } @article {pmid30149007, year = {2018}, author = {Zeng, J and Kamiyama, T and Niwa, R and King-Jones, K}, title = {The Drosophila CCR4-NOT complex is required for cholesterol homeostasis and steroid hormone synthesis.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {10-18}, doi = {10.1016/j.ydbio.2018.08.012}, pmid = {30149007}, issn = {1095-564X}, mesh = {Animals ; Carrier Proteins/metabolism ; Cholesterol/*metabolism ; Cytochrome P-450 Enzyme System/metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/enzymology/metabolism ; Ecdysone/biosynthesis ; Gene Expression Profiling/methods ; Gonadal Steroid Hormones/*biosynthesis ; Homeostasis/physiology ; Ribonucleases/*metabolism ; Transcription Factors/metabolism ; }, abstract = {CCR4-NOT is a highly conserved protein complex that regulates gene expression at multiple levels. In yeast, CCR4-NOT functions in transcriptional initiation, heterochromatin formation, mRNA deadenylation and other processes. The range of functions for Drosophila CCR4-NOT is less clear, except for a well-established role as a deadenylase for maternal mRNAs during early embryogenesis. We report here that CCR4-NOT has an essential function in the Drosophila prothoracic gland (PG), a tissue that predominantly produces the steroid hormone ecdysone. Interfering with the expression of the CCR4-NOT components twin, Pop2, Not1, and Not3 in a PG-specific manner resulted in larval arrest and a failure to initiate metamorphosis. Transcriptome analysis of PG-specific Pop2-RNAi samples revealed that Pop2 is required for the normal expression of ecdysone biosynthetic gene spookier (spok) as well as cholesterol homeostasis genes of the NPC2 family. Interestingly, dietary supplementation with ecdysone and its various sterol precursors showed that 7-dehydrocholesterol and cholesterol completely rescued the larval arrest phenotype, allowing Pop2-RNAi animals to reach pupal stage, and, to a low degree, even survival to adulthood, while the biologically active hormone, 20-Hydroxyecdysone (20E), was significantly less effective. Also, we present genetic evidence that CCR4-NOT has a nuclear function where CCR4-NOT-depleted cells exhibit aberrant chromatin and nucleoli structures. In summary, our findings indicate that the Drosophila CCR4-NOT complex has essential roles in the PG, where it is required for Drosophila steroid hormone production and cholesterol homeostasis, and likely has functions beyond a mere mRNA deadenylase in Drosophila.}, } @article {pmid30149006, year = {2018}, author = {Romer, KA and de Rooij, DG and Kojima, ML and Page, DC}, title = {Isolating mitotic and meiotic germ cells from male mice by developmental synchronization, staging, and sorting.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {19-34}, doi = {10.1016/j.ydbio.2018.08.009}, pmid = {30149006}, issn = {1095-564X}, support = {T32 GM007287/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Flow Cytometry/*methods ; Germ Cells/*cytology ; Male ; Meiosis/physiology ; Mice ; Mice, Inbred C57BL ; Spermatogenesis/physiology ; Spermatogonia/*cytology ; Testis/cytology ; Tretinoin/metabolism/pharmacology ; }, abstract = {Isolating discrete populations of germ cells from the mouse testis is challenging, because the adult testis contains germ cells at every step of spermatogenesis, in addition to somatic cells. We present a novel method for isolating precise, high-purity populations of male germ cells. We first synchronize germ cell development in vivo by manipulating retinoic acid metabolism, and perform histological staging to verify synchronization. We use fluorescence-activated cell sorting to separate the synchronized differentiating germ cells from contaminating somatic cells and undifferentiated spermatogonia. We achieve ~90% purity at each step of development from undifferentiated spermatogonia through late meiotic prophase. Utilizing this "3 S" method (synchronize, stage, and sort), we can separate germ cell types that were previously challenging or impossible to distinguish, with sufficient yield for epigenetic and biochemical studies. 3 S expands the toolkit of germ cell sorting methods, and should facilitate detailed characterization of molecular and biochemical changes that occur during the mitotic and meiotic phases of spermatogenesis.}, } @article {pmid30149005, year = {2018}, author = {Clements, R and Wright, KM}, title = {Retinal ganglion cell axon sorting at the optic chiasm requires dystroglycan.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {210-219}, pmid = {30149005}, issn = {1095-564X}, support = {P30 NS061800/NS/NINDS NIH HHS/United States ; R01 NS091027/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Axon Guidance/physiology ; Axons/metabolism ; Brain/metabolism ; Dystroglycans/*metabolism/physiology ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins/metabolism ; Optic Chiasm/metabolism ; Retina/metabolism ; Retinal Ganglion Cells/*metabolism/physiology ; Visual Pathways/metabolism ; }, abstract = {In the developing visual system, retinal ganglion cell (RGC) axons project from the retina to several distal retinorecipient regions in the brain. Several molecules have been implicated in guiding RGC axons in vivo, but the role of extracellular matrix molecules in this process remains poorly understood. Dystroglycan is a laminin-binding transmembrane protein important for formation and maintenance of the extracellular matrix and basement membranes and has previously been implicated in axon guidance in the developing spinal cord. Using two genetic models of functional dystroglycan loss, we show that dystroglycan is necessary for correct sorting of contralateral and ipsilateral RGC axons at the optic chiasm. Mis-sorted axons still target retinorecipient brain regions and persist in adult mice, even after axon pruning is complete. Our results highlight the importance of the extracellular matrix for axon sorting at an intermediate choice point in the developing visual circuit.}, } @article {pmid30147195, year = {2018}, author = {Jara, M and Frias-De-Diego, A and García-Roa, R and Saldarriaga-Córdoba, M and Harvey, LP and Hickcox, RP and Pincheira-Donoso, D}, title = {The Macroecology of Chemical Communication in Lizards: Do Climatic Factors Drive the Evolution of Signalling Glands?.}, journal = {Evolutionary biology}, volume = {45}, number = {3}, pages = {259-267}, pmid = {30147195}, issn = {0071-3260}, abstract = {Chemical communication plays a pivotal role in shaping sexual and ecological interactions among animals. In lizards, fundamental mechanisms of sexual selection such as female mate choice have rarely been shown to be influenced by quantitative phenotypic traits (e.g., ornaments), while chemical signals have been found to potentially influence multiple forms of sexual and social interactions, including mate choice and territoriality. Chemical signals in lizards are secreted by glands primarily located on the edge of the cloacae (precloacal glands, PG) and thighs (femoral glands), and whose interspecific and interclade number ranges from 0 to > 100. However, elucidating the factors underlying the evolution of such remarkable variation remains an elusive endeavour. Competing hypotheses suggest a dominant role for phylogenetic conservatism (i.e., species within clades share similar numbers of glands) or for natural selection (i.e., their adaptive diversification results in deviating numbers of glands from ancestors). Using the prolific Liolaemus lizard radiation from South America (where PG vary from 0 to 14), we present one of the largest-scale tests of both hypotheses to date. Based on climatic and phylogenetic modelling, we show a clear role for both phylogenetic inertia and adaptation underlying gland variation: (i) solar radiation, net primary productivity, topographic heterogeneity and precipitation range have a significant effect on PG variation, (ii) humid and cold environments tend to concentrate species with a higher number of glands, (iii) there is a strong phylogenetic signal that tends to conserve the number of PG within clades. Collectively, our study confirms that the inertia of niche conservatism can be broken down by the need of species facing different selection regimes to adjust their glands to suit the demands of their specific environments.}, } @article {pmid30146753, year = {2018}, author = {Cabello, FC and Cohen, SN and Curtiss, R and Dougan, G and van Embden, J and Finlay, BB and Heffron, F and Helinski, D and Hull, R and Hull, S and Isberg, R and Kopecko, DJ and Levy, S and Mekalanos, J and Ortiz, JM and Rappuoli, R and Roberts, MC and So, M and Timmis, KN}, title = {Farewell Stan Stanley Falkow: 1934-2018.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2322-2333}, doi = {10.1111/1462-2920.14308}, pmid = {30146753}, issn = {1462-2920}, } @article {pmid30146456, year = {2018}, author = {Swearingen, KE and Lindner, SE}, title = {Plasmodium Parasites Viewed through Proteomics.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {945-960}, pmid = {30146456}, issn = {1471-5007}, support = {K25 AI119229/AI/NIAID NIH HHS/United States ; R01 AI123341/AI/NIAID NIH HHS/United States ; }, abstract = {Early sequencing efforts that produced the genomes of several species of malaria parasites (Plasmodium genus) propelled transcriptomic and proteomic efforts. In this review, we focus upon some of the exciting proteomic advances from studies of Plasmodium parasites over approximately the past decade. With improvements to both instrumentation and data-processing capabilities, long-standing questions about the forms and functions of these important pathogens are rapidly being answered. In particular, global and subcellular proteomics, quantitative proteomics, and the detection of post-translational modifications have all revealed important features of the parasite's regulatory mechanisms. Finally, we provide our perspectives on future applications of proteomics to Plasmodium research, as well as suggestions for further improvement through standardization of data deposition, analysis, and accessibility.}, } @article {pmid30146326, year = {2018}, author = {Seibold, S and Cadotte, MW and MacIvor, JS and Thorn, S and Müller, J}, title = {The Necessity of Multitrophic Approaches in Community Ecology.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {754-764}, doi = {10.1016/j.tree.2018.07.001}, pmid = {30146326}, issn = {1872-8383}, abstract = {Trophic interactions are a fundamental part of ecosystems; yet, most ecological studies focus on single trophic levels and this hampers our ability to detect the underlying mechanisms structuring communities as well as the effects of environmental change. Here, we argue that the historical dominance of studying competition within trophic levels, and the focus on taxonomic groups without differentiating the trophic level, has led to the under-representation of multitrophic research in community ecology. There are many hurdles that challenge multitrophic approaches and we discuss solutions to overcome these. To advance our understanding of the fundamental drivers of community assembly and to provide the necessary guidance for managing and mitigating the effects of environmental change, we argue that ecologists should better align research with a trophically inclusive definition of a community.}, } @article {pmid30146183, year = {2018}, author = {Crow, M and Gillis, J}, title = {Co-expression in Single-Cell Analysis: Saving Grace or Original Sin?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {11}, pages = {823-831}, pmid = {30146183}, issn = {0168-9525}, support = {F32 MH114501/MH/NIMH NIH HHS/United States ; R01 LM012736/LM/NLM NIH HHS/United States ; R01 MH113005/MH/NIMH NIH HHS/United States ; }, abstract = {As a fundamental unit of life, the cell has rightfully been the subject of intense investigation throughout the history of biology. Technical innovations now make it possible to assay cellular features at genomic scale, yielding breakthroughs in our understanding of the molecular organization of tissues, and even whole organisms. As these data accumulate we will soon be faced with a new challenge: making sense of the plethora of results. Early investigations into the replicability of cell type profiles inferred from single-cell RNA sequencing data have indicated that this is likely to be surprisingly straightforward due to consistent gene co-expression. In this opinion article we discuss the evidence for this claim and its implications for interpreting cell type-specific gene expression.}, } @article {pmid30146039, year = {2018}, author = {Taucce, PPG and Canedo, C and Parreiras, JS and Drummond, LO and Nogueira-Costa, P and Haddad, CFB}, title = {Molecular phylogeny of Ischnocnema (Anura: Brachycephalidae) with the redefinition of its series and the description of two new species.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {123-146}, doi = {10.1016/j.ympev.2018.06.042}, pmid = {30146039}, issn = {1095-9513}, abstract = {We present a new phylogenetic hypothesis for Ischnocnema, a Neotropical brachycephaloid genus of ground-dwelling direct-developing frogs. We performed Bayesian inference, maximum likelihood, and maximum parsimony analyses using two nuclear (RAG1 and Tyr) and three mitochondrial genes (12S rRNA, tRNA-Val, and 16S rRNA) in a matrix comprising more than 80% of the described species. We recover Ischnocnema nanahallux outside the Ischnocnema parva series, and it is now unassigned to any species series, nor are Ischnocnema manezinho and Ischnocnema sambaqui. We propose the Ischnocnema venancioi species series to comprise Ischnocnema venancioi, Ischnocnema hoehnei, and two new species described herein (Ischnocnema parnaso sp. nov. and Ischnocnema colibri sp. nov.). Furthermore, we designate a lectotype for I. venancioi. The nuptial pad present in males is an important character in the genus, and having a large, conspicuous, and glandular-appearing nuptial pad seems to be a synapomorphy for the clade composed of the I. parva, Ischnocnema guentheri, and the newly proposed I. venancioi series.}, } @article {pmid30145366, year = {2018}, author = {Roth, A and Govaerts, C}, title = {LmrP from Lactoccoccus lactis: a tractable model to understand secondary multidrug transport in MFS.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {468-477}, doi = {10.1016/j.resmic.2018.07.006}, pmid = {30145366}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/*metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biological Transport ; Lactococcus lactis/chemistry/genetics/*metabolism ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; }, abstract = {The secondary transporter LmrP from Lactoccoccus lactis is a remarkable model to study the molecular basis of secondary multidrug transport. This review article addresses more than twenty years of research about transport activity, substrates range, conformational dynamics and mechanistic models of drug export for LmrP. Several studies have shown that the transporter alternates between inward-open and outward-open conformations and that the transition is regulated by the protonation state of key acidic residues and is further modulated by the lipid environment.}, } @article {pmid30145104, year = {2018}, author = {Buenaventura, DF and Ghinia-Tegla, MG and Emerson, MM}, title = {Fate-restricted retinal progenitor cells adopt a molecular profile and spatial position distinct from multipotent progenitor cells.}, journal = {Developmental biology}, volume = {443}, number = {1}, pages = {35-49}, doi = {10.1016/j.ydbio.2018.06.023}, pmid = {30145104}, issn = {1095-564X}, support = {G12 MD007603/MD/NIMHD NIH HHS/United States ; R01 EY024982/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/physiology ; Cell Lineage/genetics ; Chick Embryo ; Gene Expression Regulation, Developmental/genetics ; Genes, erbA/genetics ; Homeodomain Proteins/genetics ; LIM-Homeodomain Proteins/genetics ; Mice ; PAX6 Transcription Factor/genetics ; Retina/cytology/*embryology ; Retinal Cone Photoreceptor Cells/metabolism/*physiology ; Stem Cells/physiology ; Transcription Factors/genetics ; Transcriptome/genetics ; }, abstract = {During development, multipotent retinal progenitor cells generate a large number of unique cell types. Recent evidence suggests that there are fate-restricted progenitor cell states in addition to multipotent ones. Here we report a transcriptomic analysis of fate- restricted progenitor cells biased to produce cone photoreceptors and horizontal cells, marked by the THRB cis-regulatory element ThrbCRM1. Comparison to a control population enriched in multipotent progenitor cells identified several genes considered to be pan-progenitor, such as VSX2, LHX2, and PAX6, as downregulated in these fate- restricted retinal progenitor cells. This differential regulation occurs in chick and in a different restricted progenitor population in mouse suggesting that this is a conserved feature of progenitor dynamics during retinal development. S-phase labeling also revealed that nuclear positions of restricted progenitor populations occupy distinct spatial niches within the developing chick retina. Using a conserved regulatory element proximal to the VSX2 gene, a potential negative feedback mechanism from specific transcription factors enriched in cone/horizontal cell progenitor cells was identified. This study identifies conserved molecular and cellular changes that occur during the generation of fate restricted retinal progenitor cells from multipotent retinal progenitor cells.}, } @article {pmid30145038, year = {2018}, author = {Raes, J}, title = {Editorial overview: It's the ecology, stupid: microbiome research in the post-stamp collecting age.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {iv-v}, doi = {10.1016/j.mib.2018.07.008}, pmid = {30145038}, issn = {1879-0364}, } @article {pmid30144941, year = {2018}, author = {He, Y and Li, Z}, title = {Epigenetic Environmental Memories in Plants: Establishment, Maintenance, and Reprogramming.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {11}, pages = {856-866}, doi = {10.1016/j.tig.2018.07.006}, pmid = {30144941}, issn = {0168-9525}, abstract = {Plants are immobile and must respond to or endure fluctuating surroundings and diverse environmental challenges. Environmental inputs often induce chromatin modifications at various responsive genes and consequent changes in their expression. Environment-induced chromatin marks at certain loci are transmittable through cell divisions after relief from the original external signals, leading to acquired 'memorization' of environmental experiences in plants, namely epigenetic environmental memories, which enable plants to adapt to environmental changes or to perform better when events recur. Here, we review recent progress in epigenetic or chromatin-mediated environmental memories in plants, including defense priming, stress memories, and 'epigenetic memory of winter cold' or vernalization. Various advances in epigenetic mechanisms underlying plant-environment interactions highlight that plant environmental epigenetics is emerging as an important area in plant biology.}, } @article {pmid30144824, year = {2018}, author = {Imai, R and Misaka, S and Horita, S and Yokota, S and O'hashi, R and Maejima, Y and Shimomura, K}, title = {Memantine has no effect on KATP channels in pancreatic β cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {614}, pmid = {30144824}, issn = {1756-0500}, support = {26461366//Japan Society for the Promotion of Science/ ; 15K09395//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Dopamine Agents/*pharmacology ; Glucose ; Insulin ; Insulin-Secreting Cells/*drug effects ; Islets of Langerhans ; Japan ; KATP Channels/*drug effects/physiology ; Male ; Memantine/*pharmacology ; Mice ; Mice, Inbred C57BL ; }, abstract = {OBJECTIVE: Memantine, a drug for Alzheimer's disease, is considered to suppress excessive stimulation of N-methyl-D-aspartic acid receptors and to prevent neuronal death. However, a recent report indicated that the neuronal KATP channel also can become a target of memantine. The KATP channel is a key regulator of insulin secretion in pancreatic β cells. Therefore, if memantine could inhibit the KATP channel in pancreatic β cells, it would be an effective drug for both Alzheimer's disease and diabetes. However, there is no report on the effect of memantine on the KATP channel in pancreatic β cells. Therefore, we investigated whether memantine affect the blood glucose level, insulin secretion and KATP channel activity in pancreatic β cells.

RESULTS: An intraperitoneal glucose tolerance test was performed with or without memantine (1 mg/kg) injection in intact mice. Insulin secretion from isolated islets was measured under low (2 mM) and high (20 mM) glucose concentrations with or without memantine (1 μM). The effect of memantine (1 μM) on KATP channel currents in isolated pancreatic β cells was recorded using the whole-cell patch-clamp technique. Memantine had no effect on the blood glucose level, insulin secretion from isolated islets or KATP channel current in pancreatic β cells.}, } @article {pmid30144820, year = {2018}, author = {Gebretsadik, D and Haileslasie, H and Feleke, DG}, title = {Intestinal parasitosis among HIV/AIDS patients who are on anti-retroviral therapy in Kombolcha, North Central, Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {613}, pmid = {30144820}, issn = {1756-0500}, mesh = {Adult ; Anti-Retroviral Agents/*therapeutic use ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Feces ; Female ; HIV Infections/drug therapy/*parasitology ; Humans ; Intestinal Diseases, Parasitic/*complications/epidemiology ; Male ; Middle Aged ; Prevalence ; }, abstract = {OBJECTIVE: Human immunodeficiency virus (HIV) infected patients are highly vulnerable to microbial and parasitic diseases due to the immune-suppression. This study aimed to determine the prevalence and assess the associated risk factors of intestinal parasites in HIV/AIDS patients who are under anti-retroviral therapy in Kombolcha, North-Central Ethiopia.

RESULT: A total of 223 HIV sero-positive individuals who are on ART in Kombolcha Health Centre were examined for intestinal parasites. Of the total study participants 153 (68.6%) were females, 205 (91.9%) were urban resident and 116 (52.0%) were married. Intestinal parasites were detected in 31 (13.9%) of the 223 study participants. Nine different intestinal parasite species were detected and the most prevalent intestinal parasite detected was E. histolytica, which accounts 7.2% (16/223). Majority of study participants had the habit of washing their hand before meal and after toilet 215 (96.4%) and most of the study participants 126 (56.5%) had private toilet.}, } @article {pmid30144812, year = {2018}, author = {Hamed, S and Klingberg, S and Mahmud, AJ and Bradby, H}, title = {Researching health in diverse neighbourhoods: critical reflection on the use of a community research model in Uppsala, Sweden.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {612}, pmid = {30144812}, issn = {1756-0500}, support = {462-14-090//Norface Welfare State Futures Programme/ ; }, mesh = {*Cultural Diversity ; *Health Services Research ; Humans ; *Residence Characteristics ; Sweden ; }, abstract = {OBJECTIVE: A community research model developed in the United Kingdom was adopted in a multi-country study of health in diverse neighbourhoods in European cities, including Sweden. This paper describes the challenges and opportunities of using this model in Sweden.

RESULTS: In Sweden, five community researchers were recruited and trained to facilitate access to diverse groups in the two study neighbourhoods, including ethnic, religious, and linguistic minorities. Community researchers recruited participants from the neighbourhoods, and assisted during semi-structured interviews. Their local networks, and knowledge were invaluable for contextualising the study and finding participants. Various factors made it difficult to fully apply the model in Sweden. The study took place when an unprecedented number of asylum-seekers were arriving in Sweden, and potential collaborators' time was taken up in meeting their needs. Employment on short-term, temporary contracts is difficult since Swedish Universities are public authorities. Strong expectations of stable full-time employment, make flexible part-time work undesirable. The community research model was only partly successful in embedding the research project as a collaboration between community members and the University. While there was interest and some involvement from neighbourhood residents, the research remained University-led with a limited sense of community ownership.}, } @article {pmid30144805, year = {2018}, author = {Kumlachew, W and Tezera, N and Endalamaw, A}, title = {Below normal birth weight in the Northwest part of Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {611}, pmid = {30144805}, issn = {1756-0500}, mesh = {Birth Weight ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Humans ; Infant ; *Infant, Low Birth Weight ; Infant, Newborn ; Male ; Odds Ratio ; Pregnancy ; }, abstract = {OBJECTIVES: Low birth weight is one of the global agendas that have an impact on the short and long-term health status. A cross-sectional study from March 1 to April 1, 2018 was conducted. 381 mother-newborn pairs were participated. This study aimed to assess the prevalence and associated factors of low birth weight in the Northwest part of Ethiopia.

RESULTS: The prevalence of low birth weight was 14.9% (95% CI 11.7-18.9). Being preterm [adjusted odds ratio (AOR) = 4.1; 95% CI 1.7-9.9], absence of ante-natal care follow-up (AOR = 3.4; 95% CI 1.2-9.5), malaria attack during pregnancy (AOR = 4.2; 95% CI 1.6-11.1), anemia during pregnancy (AOR = 2.6; 95% CI 1.03-7.0), and lack of iron supplementation (AOR = 4.0; 95% CI 1.3-12.6) were predisposing factors to low birth weight. On the other hand, infants born from employed mothers (AOR = 0.1; 95% CI 0.01-0.92) were less likely to born with below normal birth weight. The prevalence of low birth was high as compared to WHO estimation.}, } @article {pmid30144418, year = {2018}, author = {Buitrago-Delgado, E and Schock, EN and Nordin, K and LaBonne, C}, title = {A transition from SoxB1 to SoxE transcription factors is essential for progression from pluripotent blastula cells to neural crest cells.}, journal = {Developmental biology}, volume = {444}, number = {2}, pages = {50-61}, doi = {10.1016/j.ydbio.2018.08.008}, pmid = {30144418}, issn = {1095-564X}, support = {R01 GM116538/GM/NIGMS NIH HHS/United States ; }, abstract = {The neural crest is a stem cell population unique to vertebrate embryos that gives rise to derivatives from multiple embryonic germ layers. The molecular underpinnings of potency that govern neural crest potential are highly conserved with that of pluripotent blastula stem cells, suggesting that neural crest cells may have evolved through retention of aspects of the pluripotency gene regulatory network (GRN). A striking difference in the regulatory factors utilized in pluripotent blastula cells and neural crest cells is the deployment of different sub-families of Sox transcription factors; SoxB1 factors play central roles in the pluripotency of naïve blastula and ES cells, whereas neural crest cells require SoxE function. Here we explore the shared and distinct activities of these factors to shed light on the role that this molecular hand-off of Sox factor activity plays in the genesis of neural crest and the lineages derived from it. Our findings provide evidence that SoxB1 and SoxE factors have both overlapping and distinct activities in regulating pluripotency and lineage restriction in the embryo. We hypothesize that SoxE factors may transiently replace SoxB1 factors to control pluripotency in neural crest cells, and then poise these cells to contribute to glial, chondrogenic and melanocyte lineages at stages when SoxB1 factors promote neuronal progenitor formation.}, } @article {pmid30144355, year = {2018}, author = {Phillips, RD and Peakall, R}, title = {An experimental evaluation of traits that influence the sexual behaviour of pollinators in sexually deceptive orchids.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1732-1742}, doi = {10.1111/jeb.13370}, pmid = {30144355}, issn = {1420-9101}, support = {DE150101720//Australian Research Council/ ; DP150102762//Australian Research Council/ ; }, abstract = {Pollination by sexual deception of male insects is perhaps one of the most remarkable cases of mimicry in the plant kingdom. However, understanding the influence of floral traits on pollinator behaviour in sexually deceptive plants is challenging, due to the risk of confounding changes in floral odour when manipulating morphology. Here, we investigated the floral traits influencing the sexual response of male Zaspilothynnus nigripes (Tiphiidae) wasps, a pollinator of two distantly related sexually deceptive orchids with contrasting floral architecture, Caladenia pectinata and Drakaea livida. In D. livida, the chemical sexual attractant is emitted from the labellum, whereas in C. pectinata, it is produced from the distal sepal tips, allowing manipulative experiments. When controlling for visual cues, there was no difference in long-distance attraction, although the floral odour of D. livida induced copulation more frequently than that of C. pectinata. The role of colour in pollinator sexual attraction was equivocal, indicating that colour may not be a strong constraint on the initial evolution of sexual deception. The frequency of wasp visitors landing on C. pectinata decreased when the amount of floral odour was reduced, but attempted copulation rates were enhanced when the source of floral odour was associated with the labellum. These latter variables may represent axes of selection that operate across many sexually deceptive species. Nonetheless, the observed variation in floral traits suggests flexibility among species in how sexual deception can be achieved.}, } @article {pmid30143891, year = {2018}, author = {Sun, M and Biggs, R and Hornick, J and Marko, JF}, title = {Condensin controls mitotic chromosome stiffness and stability without forming a structurally contiguous scaffold.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {4}, pages = {277-295}, doi = {10.1007/s10577-018-9584-1}, pmid = {30143891}, issn = {1573-6849}, support = {GM105847//National Institutes of Health/ ; DK107980//National Institutes of Health/ ; CA193419//National Cancer Institute/ ; MCB-1022117//National Science Foundation/ ; DMR-1611076//National Science Foundation/ ; DMR-1206868//National Science Foundation/ ; }, abstract = {During cell division, chromosomes must be folded into their compact mitotic form to ensure their segregation. This process is thought to be largely controlled by the action of condensin SMC protein complexes on chromatin fibers. However, how condensins organize metaphase chromosomes is not understood. We have combined micromanipulation of single human mitotic chromosomes, sub-nanonewton force measurement, siRNA interference of condensin subunit expression, and fluorescence microscopy, to analyze the role of condensin in large-scale chromosome organization. Condensin depletion leads to a dramatic (~ 10-fold) reduction in chromosome elastic stiffness relative to the native, non-depleted case. We also find that prolonged metaphase stalling of cells leads to overloading of chromosomes with condensin, with abnormally high chromosome stiffness. These results demonstrate that condensin is a main element controlling the stiffness of mitotic chromosomes. Isolated, slightly stretched chromosomes display a discontinuous condensing staining pattern, suggesting that condensins organize mitotic chromosomes by forming isolated compaction centers that do not form a continuous scaffold.}, } @article {pmid30143803, year = {2018}, author = {Pool, MR and Russo, I}, title = {The perplexing PEXEL protein secretory pathway.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {969-970}, doi = {10.1038/s41564-018-0235-2}, pmid = {30143803}, issn = {2058-5276}, } @article {pmid30143802, year = {2018}, author = {Lecuit, M and Nguyen, L}, title = {Lessons learnt from the emergence of Zika virus.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {966-968}, doi = {10.1038/s41564-018-0233-4}, pmid = {30143802}, issn = {2058-5276}, } @article {pmid30143801, year = {2018}, author = {Dick, T and Dartois, V}, title = {TB drug susceptibility is more than MIC.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {971-972}, doi = {10.1038/s41564-018-0226-3}, pmid = {30143801}, issn = {2058-5276}, } @article {pmid30143800, year = {2018}, author = {Hutchins, DA}, title = {Adapt to warming and catch your breath.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {973-974}, doi = {10.1038/s41564-018-0228-1}, pmid = {30143800}, issn = {2058-5276}, } @article {pmid30143799, year = {2018}, author = {Hall, EK and Bernhardt, ES and Bier, RL and Bradford, MA and Boot, CM and Cotner, JB and Del Giorgio, PA and Evans, SE and Graham, EB and Jones, SE and Lennon, JT and Locey, KJ and Nemergut, D and Osborne, BB and Rocca, JD and Schimel, JP and Waldrop, MP and Wallenstein, MD}, title = {Understanding how microbiomes influence the systems they inhabit.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {977-982}, doi = {10.1038/s41564-018-0201-z}, pmid = {30143799}, issn = {2058-5276}, abstract = {Translating the ever-increasing wealth of information on microbiomes (environment, host or built environment) to advance our understanding of system-level processes is proving to be an exceptional research challenge. One reason for this challenge is that relationships between characteristics of microbiomes and the system-level processes that they influence are often evaluated in the absence of a robust conceptual framework and reported without elucidating the underlying causal mechanisms. The reliance on correlative approaches limits the potential to expand the inference of a single relationship to additional systems and advance the field. We propose that research focused on how microbiomes influence the systems they inhabit should work within a common framework and target known microbial processes that contribute to the system-level processes of interest. Here, we identify three distinct categories of microbiome characteristics (microbial processes, microbial community properties and microbial membership) and propose a framework to empirically link each of these categories to each other and the broader system-level processes that they affect. We posit that it is particularly important to distinguish microbial community properties that can be predicted using constituent taxa (community-aggregated traits) from those properties that cannot currently be predicted using constituent taxa (emergent properties). Existing methods in microbial ecology can be applied to more explicitly elucidate properties within each of these three categories of microbial characteristics and connect them with each other. We view this proposed framework, gleaned from a breadth of research on environmental microbiomes and ecosystem processes, as a promising pathway with the potential to advance discovery and understanding across a broad range of microbiome science.}, } @article {pmid30143757, year = {2018}, author = {Cotter, KA and Rubin, MA}, title = {Sequence of events in prostate cancer.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {557-559}, doi = {10.1038/d41586-018-06029-5}, pmid = {30143757}, issn = {1476-4687}, mesh = {Humans ; Male ; *Prostatic Neoplasms ; *Receptors, Androgen ; }, } @article {pmid30143756, year = {2018}, author = {Naiman, S and Cohen, HY}, title = {Role for the longevity protein SIRT6 in primate development.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {559-560}, doi = {10.1038/d41586-018-05970-9}, pmid = {30143756}, issn = {1476-4687}, mesh = {Animals ; *Longevity ; *Macaca fascicularis ; Primates ; Sirtuins ; }, } @article {pmid30143755, year = {2018}, author = {Adelman, K and Henriques, T}, title = {Transcriptional speed bumps revealed in high resolution.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {560-561}, doi = {10.1038/d41586-018-05971-8}, pmid = {30143755}, issn = {1476-4687}, mesh = {*RNA Polymerase II ; }, } @article {pmid30143754, year = {2018}, author = {Wang, F and Matsuoka, M}, title = {Improved nutrient use gives cereal crops a boost.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {563-564}, doi = {10.1038/d41586-018-05928-x}, pmid = {30143754}, issn = {1476-4687}, mesh = {Agriculture ; Crops, Agricultural ; *Edible Grain ; *Nutrients ; Plant Development ; }, } @article {pmid30143749, year = {2018}, author = {Krump, NA and You, J}, title = {Molecular mechanisms of viral oncogenesis in humans.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {684-698}, doi = {10.1038/s41579-018-0064-6}, pmid = {30143749}, issn = {1740-1534}, support = {P30 CA016520/CA/NCI NIH HHS/United States ; R01 CA142723/CA/NCI NIH HHS/United States ; R01 CA148768/CA/NCI NIH HHS/United States ; R01 CA187718/CA/NCI NIH HHS/United States ; }, abstract = {Viral infection is a major contributor to the global cancer burden. Recent advances have revealed that seven known oncogenic viruses promote tumorigenesis through shared host cell targets and pathways. A comprehensive understanding of the principles of viral oncogenesis may enable the identification of unknown infectious aetiologies of cancer and the development of therapeutic or preventive strategies for virus-associated cancers. In this Review, we discuss the molecular mechanisms of viral oncogenesis in humans. We highlight recent advances in understanding how viral manipulation of host cellular signalling, DNA damage responses, immunity and microRNA targets promotes the initiation and development of cancer.}, } @article {pmid30143748, year = {2018}, author = {York, A}, title = {A new timeline of life's early evolution.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {582-583}, doi = {10.1038/s41579-018-0080-6}, pmid = {30143748}, issn = {1740-1534}, } @article {pmid30143581, year = {2018}, author = {Drebes Dörr, NC and Blokesch, M}, title = {Bacterial type VI secretion system facilitates niche domination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8855-8857}, pmid = {30143581}, issn = {1091-6490}, support = {55008726/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Bacteria ; Bacterial Proteins ; Bacterial Secretion Systems ; *Type VI Secretion Systems ; }, } @article {pmid30143580, year = {2018}, author = {Tiwari, S and van Tonder, AJ and Vilchèze, C and Mendes, V and Thomas, SE and Malek, A and Chen, B and Chen, M and Kim, J and Blundell, TL and Parkhill, J and Weinrick, B and Berney, M and Jacobs, WR}, title = {Arginine-deprivation-induced oxidative damage sterilizes Mycobacterium tuberculosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9779-9784}, pmid = {30143580}, issn = {1091-6490}, support = {R37 AI026170/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; 098051//Wellcome Trust/United Kingdom ; R01 AI026170/AI/NIAID NIH HHS/United States ; //Wellcome Trust/United Kingdom ; P30 CA013330/CA/NCI NIH HHS/United States ; }, mesh = {Antioxidants/metabolism ; Antitubercular Agents/pharmacology ; Arginine/*deficiency/metabolism ; DNA Damage ; Drug Resistance, Bacterial ; Flow Cytometry ; Gene Expression Profiling ; In Vitro Techniques ; Metabolic Networks and Pathways ; Mycobacterium tuberculosis/*metabolism ; *Oxidative Stress ; Reactive Oxygen Species/metabolism ; Sulfhydryl Compounds/metabolism ; }, abstract = {Reactive oxygen species (ROS)-mediated oxidative stress and DNA damage have recently been recognized as contributing to the efficacy of most bactericidal antibiotics, irrespective of their primary macromolecular targets. Inhibitors of targets involved in both combating oxidative stress as well as being required for in vivo survival may exhibit powerful synergistic action. This study demonstrates that the de novo arginine biosynthetic pathway in Mycobacterium tuberculosis (Mtb) is up-regulated in the early response to the oxidative stress-elevating agent isoniazid or vitamin C. Arginine deprivation rapidly sterilizes the Mtb de novo arginine biosynthesis pathway mutants ΔargB and ΔargF without the emergence of suppressor mutants in vitro as well as in vivo. Transcriptomic and flow cytometry studies of arginine-deprived Mtb have indicated accumulation of ROS and extensive DNA damage. Metabolomics studies following arginine deprivation have revealed that these cells experienced depletion of antioxidant thiols and accumulation of the upstream metabolite substrate of ArgB or ArgF enzymes. ΔargB and ΔargF were unable to scavenge host arginine and were quickly cleared from both immunocompetent and immunocompromised mice. In summary, our investigation revealed in vivo essentiality of the de novo arginine biosynthesis pathway for Mtb and a promising drug target space for combating tuberculosis.}, } @article {pmid30143579, year = {2018}, author = {Costentin, C and Savéant, JM and Tard, C}, title = {Ligand "noninnocence" in coordination complexes vs. kinetic, mechanistic, and selectivity issues in electrochemical catalysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9104-9109}, pmid = {30143579}, issn = {1091-6490}, abstract = {The world of coordination complexes is currently stimulated by the quest for efficient catalysts for the electrochemical reactions underlying modern energy and environmental challenges. Even in the case of a multielectron-multistep process, catalysis starts with uptake or removal of one electron from the resting state of the catalyst. If this first step is an outer-sphere electron transfer (triggering a "redox catalysis" process), the electron distribution over the metal and the ligand is of minor importance. This is no longer the case with "chemical catalysis," in which the active catalyst reacts with the substrate in an inner-sphere manner, often involving the transient formation of a catalyst-substrate adduct. The fact that, in most cases, the ligand is "noninnocent," in the sense that the electron density and charge gained (or removed) from the resting state of the catalyst are shared between the metal and the ligand, has become common-place knowledge over the last half-century. Insistent focus on a large degree of noninnocence of the ligand in the resting state of the catalyst, even robustly validated by spectroscopic techniques, may lead to undermining the essential role of the metal when such essential issues as kinetics, mechanisms, and product selectivity are dealt with. These points are general in scope, but their discussion is eased by adequately documented examples. This is the case for reactions involving metalloporphyrins as well as vitamin B12 derivatives and similar cobalt complexes for which a wealth of experimental data is available.}, } @article {pmid30143323, year = {2018}, author = {Stein-O'Brien, GL and Arora, R and Culhane, AC and Favorov, AV and Garmire, LX and Greene, CS and Goff, LA and Li, Y and Ngom, A and Ochs, MF and Xu, Y and Fertig, EJ}, title = {Enter the Matrix: Factorization Uncovers Knowledge from Omics.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {10}, pages = {790-805}, doi = {10.1016/j.tig.2018.07.003}, pmid = {30143323}, issn = {0168-9525}, support = {R01 CA177669/CA/NCI NIH HHS/United States ; U01 CA212007/CA/NCI NIH HHS/United States ; }, abstract = {Omics data contain signals from the molecular, physical, and kinetic inter- and intracellular interactions that control biological systems. Matrix factorization (MF) techniques can reveal low-dimensional structure from high-dimensional data that reflect these interactions. These techniques can uncover new biological knowledge from diverse high-throughput omics data in applications ranging from pathway discovery to timecourse analysis. We review exemplary applications of MF for systems-level analyses. We discuss appropriate applications of these methods, their limitations, and focus on the analysis of results to facilitate optimal biological interpretation. The inference of biologically relevant features with MF enables discovery from high-throughput data beyond the limits of current biological knowledge - answering questions from high-dimensional data that we have not yet thought to ask.}, } @article {pmid30143059, year = {2018}, author = {Etefa, MM and Teklu, MG and Teshome, DF}, title = {Work related stress and associated factors among Huajian shoe manufacturing employees in Dukem town, central Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {610}, pmid = {30143059}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Ethiopia ; Female ; Humans ; Male ; *Manufacturing and Industrial Facilities ; *Occupational Stress ; Odds Ratio ; Shoes ; Young Adult ; }, abstract = {OBJECTIVE: The objective of this study was to assess the prevalence of work-related stress (WRS) and its determinants among Huajian shoe manufacturing company employees in Dukem town, central Ethiopia. An institutional-based cross-sectional study was conducted from February to March 2016. Data were collected using pretested structured interviewer-administered questionnaires.

RESULTS: The mean age of the participants, 56.2% of whom were male was 25 (SD ± 5) years. The overall prevalence of work-related stress was 40.4% (95% CI 35.7, 45.3). Poor organizational support (adjusted odds ratio (AOR) 2.40, 95% CI 1.39, 4.77), inadequate work experience (AOR 3.77, 95% CI 1.68, 8.45), poor salary (AOR 7.04, 95% CI 3.39, 14.59), long working hours (AOR 3.40, 95% CI 2.00, 5.79), overtime work (AOR 2.24, 95% CI 1.10, 4.61), and poor physical environment (AOR 2.44, 95% CI 1.42, 4.19) were factors significantly associated with the stress. The prevalence of the stress was higher than what can be expected of many such employees. Poor organizational support, inadequate work experience, poor salary offers, long working hours, overtime work, and poor physical environment were significantly and independently associated with WRS. Establishing a functional collective agreement between employer and an employee trade union are needed to improve the problem.}, } @article {pmid30143055, year = {2018}, author = {Chiarello, M and Auguet, JC and Bettarel, Y and Bouvier, C and Claverie, T and Graham, NAJ and Rieuvilleneuve, F and Sucré, E and Bouvier, T and Villéger, S}, title = {Skin microbiome of coral reef fish is highly variable and driven by host phylogeny and diet.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {147}, pmid = {30143055}, issn = {2049-2618}, mesh = {Animal Feed ; Animals ; Bacteria/*classification/genetics ; Biodiversity ; Coral Reefs ; Fishes/classification/*microbiology ; Humans ; Metagenomics/*methods ; Microbiota ; Phylogeny ; Plankton/microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; Skin/microbiology ; Species Specificity ; }, abstract = {BACKGROUND: The surface of marine animals is covered by abundant and diversified microbial communities, which have major roles for the health of their host. While such microbiomes have been deeply examined in marine invertebrates such as corals and sponges, the microbiomes living on marine vertebrates have received less attention. Specifically, the diversity of these microbiomes, their variability among species, and their drivers are still mostly unknown, especially among the fish species living on coral reefs that contribute to key ecosystem services while they are increasingly affected by human activities. Here, we investigated these knowledge gaps analyzing the skin microbiome of 138 fish individuals belonging to 44 coral reef fish species living in the same area.

RESULTS: Prokaryotic communities living on the skin of coral reef fishes are highly diverse, with on average more than 600 OTUs per fish, and differ from planktonic microbes. Skin microbiomes varied between fish individual and species, and interspecific differences were slightly coupled to the phylogenetic affiliation of the host and its ecological traits.

CONCLUSIONS: These results highlight that coral reef biodiversity is greater than previously appreciated, since the high diversity of macro-organisms supports a highly diversified microbial community. This suggest that beyond the loss of coral reefs-associated macroscopic species, anthropic activities on coral reefs could also lead to a loss of still unexplored host-associated microbial diversity, which urgently needs to be assessed.}, } @article {pmid30143050, year = {2018}, author = {Mangrio, E and Zdravkovic, S}, title = {Crowded living and its association with mental ill-health among recently-arrived migrants in Sweden: a quantitative study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {609}, pmid = {30143050}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Afghanistan/ethnology ; Aged ; Aged, 80 and over ; *Crowding ; Female ; *Health Status ; Humans ; Iraq/ethnology ; Male ; Middle Aged ; Sweden ; Syria/ethnology ; Transients and Migrants/*psychology ; Young Adult ; }, abstract = {OBJECTIVE: Housing and neighbourhood conditions are widely acknowledged important social determinants of health and health inequalities that persist in developed countries despite general improvements in health outcomes across populations. Previous research has investigated what effect crowded living conditions have on mental health and concluded that women living in crowded conditions were more likely to suffer from depression. In contrast, men living in the same conditions responded with withdrawal or aggression. To the best of our knowledge, only a few studies have examined the association between recently-arrived migrants living in crowded conditions and poor mental health. The aim of this study was to investigate the association between crowded living conditions among recently-arrived migrants in Sweden and mental ill-health. The result is based on 681 migrants who completed and returned questionnaires in 2015-2016.

RESULTS: The analyses, independent of gender, resulted in a significant unadjusted odds ratio of 1.46 (95% CI 1.05-2.03); even after adjustments were made, the association remained significant OR 1.47 (1.05-2.07). When adding stability in housing into the adjustment-model, the OR did not remain significant OR 1.40 (0.99-1.99), P-value 0.061.}, } @article {pmid30143048, year = {2018}, author = {Vazquez-Hernandez, C and Loza, A and Gutierrez-Rios, RM}, title = {Reactant pairs and reaction organization patterns produced by a new rule-based approach.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {608}, pmid = {30143048}, issn = {1756-0500}, support = {IN202118//PAPIIT-UNAM/ ; }, mesh = {Biosynthetic Pathways ; *Computational Biology ; *Enzymes ; Humans ; *Metabolic Networks and Pathways ; }, abstract = {OBJECTIVES: Improvements in bioinformatics applications for the enzyme identification of biochemical reactions, enzyme classifications, mining for specific inhibitors and pathfinding require the accurate computational detection of reaction similarity. We provide a set of substrate-product pairs, clustered by reactions that share similar chemical transformation patterns, for which accuracy was calculated, comparing this set with manually curated data sets.

DATA DESCRIPTION: The data were analyzed by a new method that naturally split each reaction into compound pairs and loner compounds, which we called architectures (Vazquez-Hernandez et al. in BMC Syst Biol 12:63, 2018). The data include a set of 7491 curated reactions from the KEGG-Ligand data set. The data are presented in two formats, a string format and a tree structure, both of which reflect the splitting process and the final architectures of each reaction. We are also reporting sets of reactions that show similar splitting patterns naturally grouped into clusters of tree structures. The compound pairs in each cluster were compared with the reactant pairs proposed by the KEGG-RCLASS data set, and a match precision value is also provided. These data were collected with the aim of providing research with a confident set of reactant pairs that is useful for selecting between alternative substrate-product pairs predicted by pathfinders.}, } @article {pmid30142431, year = {2018}, author = {Issotta, F and Moya-Beltrán, A and Mena, C and Covarrubias, PC and Thyssen, C and Bellenberg, S and Sand, W and Quatrini, R and Vera, M}, title = {Insights into the biology of acidophilic members of the Acidiferrobacteraceae family derived from comparative genomic analyses.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {608-617}, doi = {10.1016/j.resmic.2018.08.001}, pmid = {30142431}, issn = {1769-7123}, mesh = {DNA, Bacterial/genetics ; Gammaproteobacteria/classification/*genetics/isolation & purification/metabolism ; *Genome, Bacterial ; Genomics ; Iron/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sulfur/metabolism ; }, abstract = {The family Acidiferrobacteraceae (order Acidiferrobacterales) currently contains Gram negative, neutrophilic sulfur oxidizers such as Sulfuricaulis and Sulfurifustis, as well as acidophilic iron and sulfur oxidizers belonging to the Acidiferrobacter genus. The diversity and taxonomy of the genus Acidiferrobacter has remained poorly explored. Although several metagenome and bioleaching studies have identified its presence worldwide, only two strains, namely Acidiferrobacter thiooxydans DSM 2932T, and Acidiferrobacter spp. SP3/III have been isolated and made publically available. Using 16S rRNA sequence data publically available for the Acidiferrobacteraceae, we herein shed light into the molecular taxonomy of this family. Results obtained support the presence of three clades Acidiferrobacter, Sulfuricaulis and Sulfurifustis. Genomic analyses of the genome sequences of A. thiooxydansT and Acidiferrobacter spp. SP3/III indicate that ANI relatedness between the SPIII/3 strain and A. thiooxydansT is below 95-96%, supporting the classification of strain SP3/III as a new species within this genus. In addition, approximately 70% of Acidiferrobacter sp. SPIII/3 predicted genes have a conserved ortholog in A. thiooxydans strains. A comparative analysis of iron, sulfur oxidation pathways, genome plasticity and cell-cell communication mechanisms of Acidiferrobacter spp. are also discussed.}, } @article {pmid30141771, year = {2018}, author = {Chen, LL and Chen, F and Zhao, HZ and Feng, ZZ and Zhang, H and Huang, X}, title = {Aestuariimicrobium soli sp. nov., isolated from farmland soil, and emended description of the genus Aestuariimicrobium.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3296-3300}, doi = {10.1099/ijsem.0.002986}, pmid = {30141771}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; *Farms ; Fatty Acids/chemistry ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Propionibacteriaceae/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-reaction-positive, catalase-positive, non-spore-forming and short rod- or oval-shaped bacterial strain, designated D6T, was isolated from farmland soil in Xuancheng, Anhui Province, China. Growth occurred at 4-37 °C (optimum, 30 °C), at pH 6.5-8.5 (optimum, 7.0) and with 0-7 % (w/v) NaCl (optimum, 0.5 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain D6T was most closely related to Aestuariimicrobium kwangyangense DSM 21549T (98.47 %), followed by Tessaracoccus rhinocerotis YIM 101269T (94.46 %). Strain D6T had a cell-wall peptidoglycan based on ll-diaminopimelic acid. MK-9(H4) was the predominant menaquinone. The major fatty acids of strain D6T were anteiso-C15 : 0, iso-C15 : 0 and summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B). The major polar lipids were a lipid, glycolipid and phospholipid. The DNA G+C content was 69.2 mol% and strain D6T showed low DNA-DNA relatedness to A. kwangyangense DSM 21549T (36.45±0.42 %). Based on these genotypic and phenotypic data, strain D6T represents a novel species in the genus Aestuariimicrobium, for which the name Aestuariimicrobium soli sp. nov. is proposed. The type strain is D6T (=KCTC 39995T=DSM 105824T). An emended description of the genus Aestuariimicrobium is presented.}, } @article {pmid30141770, year = {2018}, author = {Yin, Q and Liang, J and Zhang, L and Ma, K and Hu, ZL and Zhang, Y and Xu, Y}, title = {Acuticoccus kandeliae sp. nov., isolated from rhizosphere soil of the mangrove plant Kandelia, and emended description of Acuticoccus yangtzensis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3316-3321}, doi = {10.1099/ijsem.0.002990}, pmid = {30141770}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hong Kong ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhizophoraceae/*microbiology ; *Rhizosphere ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A novel bacterial strain, J103T, was isolated from rhizosphere soil of the mangrove plant Kandelia in Mai Po Inner Deep Bay Ramsar Site, Hong Kong. The strain was aerobic, Gram-stain-negative, oval-shaped with folds in the middle, non-motile and non-spore-forming. It grew at temperatures of 20-30 °C (optimum, 25-30 °C), at pH 6.0-9.0 (optimum pH 6.0) and at NaCl concentrations of 0.5-5.0 % (w/v) (optimum 1.0-2.0 %). Strain J103T was able to reduce nitrate to nitrite, and hydrolyse urea, Tween 40 and Tween 60. The major polar lipids were aminolipid, glycolipid, phosphatidylcholine and phosphatidylglycerol. The major fatty acids were C18 : 1ω7c and C19 : 0 cyclo ω8c. The respiratory quinone was Q-10. The DNA G+C content was 68.5 mol%. Sequence analysis of the 16S rRNA gene indicated that strain J103T belongs to the genus Acuticoccus, within the family Rhodobacteraceae. The closest phylogenetic neighbour was Acuticoccus yangtzensis JL1095T, showing 96.2 % 16S rRNA gene sequence similarity. The genome size of strain J103T was 6 478 100 bp. The average nucleotide identity and digital DNA-DNA hybridization values between strain J103T and Acuticoccus yangtzensis JL1095T were 75.44 and 16.43 %, respectively. Characterization based on phylogenetic, phenotypic, chemotaxonomic and genomic evidence demonstrated that strain J103T represents a novel species of the genus Acuticoccus, for which the name Acuticoccus kandeliae sp. nov. is proposed. The type strain is J103T (=DSM 104434T=MCCC 1K03288T).}, } @article {pmid30141769, year = {2018}, author = {Osman, G and Wang, Z and Wang, N and Shayimu, G and Hou, M and Guo, W and Yang, X}, title = {Pontibacter silvestris sp. nov., isolated from the soil of a Populus euphratica forest and emended description of the genus Pontibacter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3243-3247}, doi = {10.1099/ijsem.0.002972}, pmid = {30141769}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Populus/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain XAAS-R86T, a Gram-stain-negative, short rod-shaped, non-motile, aerobic bacterium, was isolated from a Populus euphratica forest near the city of Hotan, Xinjiang, PR China. The cells were found to be positive for catalase and oxidase activities. Growth occurred optimally at 28-30 °C, pH 7.0-7.5 and in the presence of 0.5-2.0 % NaCl (w/v). The results of phylogenetic analysis of the 16S rRNA gene indicated that XAAS-R86T represents a member of the genus Pontibacter within the family Hymenobacteraceae. Pontibacter akesuensis CCTCC AB 206086T is the most closely related species with a validly published name, based on 16S rRNA gene sequence identity (95.7 %). The DNA G+C content of the strain is 43.9 mol%. The main respiratory quinone is MK-7 and the major cellular fatty acids are summed feature 4 (iso-C17 : 1I and/or anteiso-C17 : 1B) and iso-C15 : 0 and its major polar lipids are phosphatidylethanolamine and two unidentified lipids. On the basis of the results of tests performed using a polyphasic approach, XAAS-R86T represents a novel species of the genus Pontibacter, for which the name Pontibactersilvestris sp. nov. is proposed, with the type strain XAAS-R86T (=CCTCC AB 2017165T=KCTC 62047T).}, } @article {pmid30141768, year = {2018}, author = {Tian, Y and Han, C and Zhao, J and Shi, H and Hu, J and Jiang, S and Han, X and Wang, X and Xiang, W}, title = {Streptomyces triticisoli sp. nov., a novel actinomycete isolated from rhizosphere soil of wheat (Triticum aestivum L.).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3327-3332}, doi = {10.1099/ijsem.0.002993}, pmid = {30141768}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; Triticum/*microbiology ; Vitamin K 2/chemistry ; }, abstract = {A novel actinomycete, designated strain NEAU-DSCPA1-4-4T, was isolated from rhizosphere soil of wheat and characterized using a polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the organism should be assigned to the genus Streptomyces. The strain formed a monophyletic clade with its closest relatives, Streptomyces ghanaensis DSM 40746T (97.7 % 16S rRNA gene sequence similarity) and Streptomyces viridosporus DSM 40243T (97.6 %). Similarly, chemotaxonomic data, including major menaquinones, fatty acid compositions and polar lipid profile, also supported the placement of strain NEAU-DSCPA1-4-4T in the genus Streptomyces. However, DNA-DNA relatedness, physiological and biochemical data showed that strain NEAU-DSCPA1-4-4T could be distinguished from its closest relatives. Therefore, we propose that strain NEAU-DSCPA1-4-4T represents a novel species of the genus Streptomyces, for which the name Streptomycestriticisoli sp. nov. is proposed, with NEAU-DSCPA1-4-4T (=CCTCC AA 2017025T=DSM 105118T) as the type strain.}, } @article {pmid30139921, year = {2018}, author = {Mirkhalaf, M and Zhou, T and Barthelat, F}, title = {Simultaneous improvements of strength and toughness in topologically interlocked ceramics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9128-9133}, pmid = {30139921}, issn = {1091-6490}, abstract = {Topologically interlocked materials (TIMs) are an emerging class of architectured materials based on stiff building blocks of well-controlled geometries which can slide, rotate, or interlock collectively providing a wealth of tunable mechanisms, precise structural properties, and functionalities. TIMs are typically 10 times more impact resistant than their monolithic form, but this improvement usually comes at the expense of strength. Here we used 3D printing and replica casting to explore 15 designs of architectured ceramic panels based on platonic shapes and their truncated versions. We tested the panels in quasi-static and impact conditions with stereoimaging, image correlation, and 3D reconstruction to monitor the displacements and rotations of individual blocks. We report a design based on octahedral blocks which is not only tougher (50×) but also stronger (1.2×) than monolithic plates of the same material. This result suggests that there is no upper bound for strength and toughness in TIMs, unveiling their tremendous potential as structural and multifunctional materials. Based on our experiments, we propose a nondimensional "interlocking parameter" which could guide the exploration of future architectured systems.}, } @article {pmid30139920, year = {2018}, author = {Ahmed, ASI and Dong, K and Liu, J and Wen, T and Yu, L and Xu, F and Kang, X and Osman, I and Hu, G and Bunting, KM and Crethers, D and Gao, H and Zhang, W and Liu, Y and Wen, K and Agarwal, G and Hirose, T and Nakagawa, S and Vazdarjanova, A and Zhou, J}, title = {Long noncoding RNA NEAT1 (nuclear paraspeckle assembly transcript 1) is critical for phenotypic switching of vascular smooth muscle cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8660-E8667}, pmid = {30139920}, issn = {1091-6490}, support = {P30 CA091842/CA/NCI NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; R01 HL109605/HL/NHLBI NIH HHS/United States ; R01 HL132164/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell Movement/genetics ; Cell Proliferation/genetics ; Cells, Cultured ; *Gene Expression Regulation ; Humans ; Mice, Inbred C57BL ; Mice, Knockout ; Muscle, Smooth, Vascular/cytology ; Myocytes, Smooth Muscle/*metabolism ; Neointima/genetics/metabolism ; Phenotype ; RNA Interference ; RNA, Long Noncoding/*genetics ; Rats ; Vascular System Injuries/genetics/metabolism/pathology ; }, abstract = {In response to vascular injury, vascular smooth muscle cells (VSMCs) may switch from a contractile to a proliferative phenotype thereby contributing to neointima formation. Previous studies showed that the long noncoding RNA (lncRNA) NEAT1 is critical for paraspeckle formation and tumorigenesis by promoting cell proliferation and migration. However, the role of NEAT1 in VSMC phenotypic modulation is unknown. Herein we showed that NEAT1 expression was induced in VSMCs during phenotypic switching in vivo and in vitro. Silencing NEAT1 in VSMCs resulted in enhanced expression of SM-specific genes while attenuating VSMC proliferation and migration. Conversely, overexpression of NEAT1 in VSMCs had opposite effects. These in vitro findings were further supported by in vivo studies in which NEAT1 knockout mice exhibited significantly decreased neointima formation following vascular injury, due to attenuated VSMC proliferation. Mechanistic studies demonstrated that NEAT1 sequesters the key chromatin modifier WDR5 (WD Repeat Domain 5) from SM-specific gene loci, thereby initiating an epigenetic "off" state, resulting in down-regulation of SM-specific gene expression. Taken together, we demonstrated an unexpected role of the lncRNA NEAT1 in regulating phenotypic switching by repressing SM-contractile gene expression through an epigenetic regulatory mechanism. Our data suggest that NEAT1 is a therapeutic target for treating occlusive vascular diseases.}, } @article {pmid30139919, year = {2018}, author = {Young, OR and Webster, DG and Cox, ME and Raakjær, J and Blaxekjær, LØ and Einarsson, N and Virginia, RA and Acheson, J and Bromley, D and Cardwell, E and Carothers, C and Eythórsson, E and Howarth, RB and Jentoft, S and McCay, BJ and McCormack, F and Osherenko, G and Pinkerton, E and van Ginkel, R and Wilson, JA and Rivers, L and Wilson, RS}, title = {Moving beyond panaceas in fisheries governance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9065-9073}, pmid = {30139919}, issn = {1091-6490}, mesh = {Fisheries/*legislation & jurisprudence/*organization & administration/*standards ; }, abstract = {In fisheries management-as in environmental governance more generally-regulatory arrangements that are thought to be helpful in some contexts frequently become panaceas or, in other words, simple formulaic policy prescriptions believed to solve a given problem in a wide range of contexts, regardless of their actual consequences. When this happens, management is likely to fail, and negative side effects are common. We focus on the case of individual transferable quotas to explore the panacea mindset, a set of factors that promote the spread and persistence of panaceas. These include conceptual narratives that make easy answers like panaceas seem plausible, power disconnects that create vested interests in panaceas, and heuristics and biases that prevent people from accurately assessing panaceas. Analysts have suggested many approaches to avoiding panaceas, but most fail to conquer the underlying panacea mindset. Here, we suggest the codevelopment of an institutional diagnostics toolkit to distill the vast amount of information on fisheries governance into an easily accessible, open, on-line database of checklists, case studies, and related resources. Toolkits like this could be used in many governance settings to challenge users' understandings of a policy's impacts and help them develop solutions better tailored to their particular context. They would not replace the more comprehensive approaches found in the literature but would rather be an intermediate step away from the problem of panaceas.}, } @article {pmid30139918, year = {2018}, author = {Stolier, RM and Hehman, E and Keller, MD and Walker, M and Freeman, JB}, title = {The conceptual structure of face impressions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9210-9215}, pmid = {30139918}, issn = {1091-6490}, support = {F31 MH114505/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; *Cognition ; Emotions ; *Face ; Female ; Humans ; Male ; Middle Aged ; *Models, Theoretical ; *Personality ; }, abstract = {Humans seamlessly infer the expanse of personality traits from others' facial appearance. These facial impressions are highly intercorrelated within a structure known as "face trait space." Research has extensively documented the facial features that underlie face impressions, thus outlining a bottom-up fixed architecture of face impressions, which cannot account for important ways impressions vary across perceivers. Classic theory in impression formation emphasized that perceivers use their lay conceptual beliefs about how personality traits correlate to form initial trait impressions, for instance, where trustworthiness of a target may inform impressions of their intelligence to the extent one believes the two traits are related. This considered, we explore the possibility that this lay "conceptual trait space"-how perceivers believe personality traits correlate in others-plays a role in face impressions, tethering face impressions to one another, thus shaping face trait space. In study 1, we found that conceptual and face trait space explain considerable variance in each other. In study 2, we found that participants with stronger conceptual associations between two traits judged those traits more similarly in faces. Importantly, using a face image classification task, we found in study 3 that participants with stronger conceptual associations between two traits used more similar facial features to make those two face trait impressions. Together, these findings suggest lay beliefs of how personality traits correlate may underlie trait impressions, and thus face trait space. This implies face impressions are not only derived bottom up from facial features, but also shaped by our conceptual beliefs.}, } @article {pmid30139917, year = {2018}, author = {Lahvic, JL and Ammerman, M and Li, P and Blair, MC and Stillman, ER and Fast, EM and Robertson, AL and Christodoulou, C and Perlin, JR and Yang, S and Chiang, N and Norris, PC and Daily, ML and Redfield, SE and Chan, IT and Chatrizeh, M and Chase, ME and Weis, O and Zhou, Y and Serhan, CN and Zon, LI}, title = {Specific oxylipins enhance vertebrate hematopoiesis via the receptor GPR132.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9252-9257}, pmid = {30139917}, issn = {1091-6490}, support = {U01 HL134812/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P01 GM095467/GM/NIGMS NIH HHS/United States ; U01 HL100001/HL/NHLBI NIH HHS/United States ; P01 HL032262/HL/NHLBI NIH HHS/United States ; R01 HL048801/HL/NHLBI NIH HHS/United States ; R24 DK092760/DK/NIDDK NIH HHS/United States ; F31 HL129517/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle Proteins/genetics/*metabolism ; Cells, Cultured ; Hematopoiesis/*drug effects/genetics ; Mice ; Mice, Knockout ; *Oxylipins/chemistry/pharmacology ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Signal Transduction/*drug effects/genetics ; Structure-Activity Relationship ; Zebrafish ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Epoxyeicosatrienoic acids (EETs) are lipid-derived signaling molecules with cardioprotective and vasodilatory actions. We recently showed that 11,12-EET enhances hematopoietic induction and engraftment in mice and zebrafish. EETs are known to signal via G protein-coupled receptors, with evidence supporting the existence of a specific high-affinity receptor. Identification of a hematopoietic-specific EET receptor would enable genetic interrogation of EET signaling pathways, and perhaps clinical use of this molecule. We developed a bioinformatic approach to identify an EET receptor based on the expression of G protein-coupled receptors in cell lines with differential responses to EETs. We found 10 candidate EET receptors that are expressed in three EET-responsive cell lines, but not expressed in an EET-unresponsive line. Of these, only recombinant GPR132 showed EET-responsiveness in vitro, using a luminescence-based β-arrestin recruitment assay. Knockdown of zebrafish gpr132b prevented EET-induced hematopoiesis, and marrow from GPR132 knockout mice showed decreased long-term engraftment capability. In contrast to high-affinity EET receptors, GPR132 is reported to respond to additional hydroxy-fatty acids in vitro, and we found that these same hydroxy-fatty acids enhance hematopoiesis in the zebrafish. We conducted structure-activity relationship analyses using both cell culture and zebrafish assays on diverse medium-chain fatty acids. Certain oxygenated, unsaturated free fatty acids showed high activation of GPR132, whereas unoxygenated or saturated fatty acids had lower activity. Absence of the carbon-1 position carboxylic acid prevented activity, suggesting that this moiety is required for receptor activation. GPR132 responds to a select panel of oxygenated polyunsaturated fatty acids to enhance both embryonic and adult hematopoiesis.}, } @article {pmid30139916, year = {2018}, author = {May, KL and Grabowicz, M}, title = {The bacterial outer membrane is an evolving antibiotic barrier.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8852-8854}, pmid = {30139916}, issn = {1091-6490}, mesh = {*Anti-Bacterial Agents ; *Bacteria ; Bacterial Outer Membrane Proteins ; Cell Membrane ; Cell Membrane Permeability/drug effects ; }, } @article {pmid30139915, year = {2018}, author = {Lancaster, J and Khrimian, A and Young, S and Lehner, B and Luck, K and Wallingford, A and Ghosh, SKB and Zerbe, P and Muchlinski, A and Marek, PE and Sparks, ME and Tokuhisa, JG and Tittiger, C and Köllner, TG and Weber, DC and Gundersen-Rindal, DE and Kuhar, TP and Tholl, D}, title = {De novo formation of an aggregation pheromone precursor by an isoprenyl diphosphate synthase-related terpene synthase in the harlequin bug.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8634-E8641}, pmid = {30139915}, issn = {1091-6490}, mesh = {Alkyl and Aryl Transferases/classification/genetics/*metabolism ; Animals ; Biosynthetic Pathways/genetics ; Heteroptera/enzymology/genetics/*metabolism ; Insect Proteins/chemistry/genetics/*metabolism ; Male ; Models, Molecular ; Molecular Structure ; Pheromones/chemistry/*metabolism ; Phylogeny ; Polyisoprenyl Phosphates/metabolism ; Protein Domains ; Sesquiterpenes/chemistry/*metabolism ; Stereoisomerism ; }, abstract = {Insects use a diverse array of specialized terpene metabolites as pheromones in intraspecific interactions. In contrast to plants and microbes, which employ enzymes called terpene synthases (TPSs) to synthesize terpene metabolites, limited information from few species is available about the enzymatic mechanisms underlying terpene pheromone biosynthesis in insects. Several stink bugs (Hemiptera: Pentatomidae), among them severe agricultural pests, release 15-carbon sesquiterpenes with a bisabolene skeleton as sex or aggregation pheromones. The harlequin bug, Murgantia histrionica, a specialist pest of crucifers, uses two stereoisomers of 10,11-epoxy-1-bisabolen-3-ol as a male-released aggregation pheromone called murgantiol. We show that MhTPS (MhIDS-1), an enzyme unrelated to plant and microbial TPSs but with similarity to trans-isoprenyl diphosphate synthases (IDS) of the core terpene biosynthetic pathway, catalyzes the formation of (1S,6S,7R)-1,10-bisaboladien-1-ol (sesquipiperitol) as a terpene intermediate in murgantiol biosynthesis. Sesquipiperitol, a so-far-unknown compound in animals, also occurs in plants, indicating convergent evolution in the biosynthesis of this sesquiterpene. RNAi-mediated knockdown of MhTPS mRNA confirmed the role of MhTPS in murgantiol biosynthesis. MhTPS expression is highly specific to tissues lining the cuticle of the abdominal sternites of mature males. Phylogenetic analysis suggests that MhTPS is derived from a trans-IDS progenitor and diverged from bona fide trans-IDS proteins including MhIDS-2, which functions as an (E,E)-farnesyl diphosphate (FPP) synthase. Structure-guided mutagenesis revealed several residues critical to MhTPS and MhFPPS activity. The emergence of an IDS-like protein with TPS activity in M. histrionica demonstrates that de novo terpene biosynthesis evolved in the Hemiptera in an adaptation for intraspecific communication.}, } @article {pmid30139914, year = {2018}, author = {Barrett, ADT}, title = {The reemergence of yellow fever.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {847-848}, doi = {10.1126/science.aau8225}, pmid = {30139914}, issn = {1095-9203}, mesh = {Communicable Diseases, Emerging/*epidemiology ; Disease Outbreaks ; Humans ; Yellow Fever/*epidemiology ; }, } @article {pmid30139913, year = {2018}, author = {Onuchic, V and Lurie, E and Carrero, I and Pawliczek, P and Patel, RY and Rozowsky, J and Galeev, T and Huang, Z and Altshuler, RC and Zhang, Z and Harris, RA and Coarfa, C and Ashmore, L and Bertol, JW and Fakhouri, WD and Yu, F and Kellis, M and Gerstein, M and Milosavljevic, A}, title = {Allele-specific epigenome maps reveal sequence-dependent stochastic switching at regulatory loci.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {}, pmid = {30139913}, issn = {1095-9203}, support = {R01 HG008155/HG/NHGRI NIH HHS/United States ; R01 GM113708/GM/NIGMS NIH HHS/United States ; U01 HG007610/HG/NHGRI NIH HHS/United States ; U01 DA025956/DA/NIDA NIH HHS/United States ; R15 GM122030/GM/NIGMS NIH HHS/United States ; U54 DA036134/DA/NIDA NIH HHS/United States ; U24 HG009446/HG/NHGRI NIH HHS/United States ; T32 GM008307/GM/NIGMS NIH HHS/United States ; R01 MH109978/MH/NIMH NIH HHS/United States ; }, mesh = {Alleles ; *Allelic Imbalance ; Binding Sites ; CpG Islands ; *DNA Methylation ; Disease/*genetics ; *Epigenesis, Genetic ; Gene Regulatory Networks ; Genetic Loci ; *Genome, Human ; Genome-Wide Association Study ; Humans ; *Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Sulfites/chemistry ; Transcription Factors/metabolism ; }, abstract = {To assess the impact of genetic variation in regulatory loci on human health, we constructed a high-resolution map of allelic imbalances in DNA methylation, histone marks, and gene transcription in 71 epigenomes from 36 distinct cell and tissue types from 13 donors. Deep whole-genome bisulfite sequencing of 49 methylomes revealed sequence-dependent CpG methylation imbalances at thousands of heterozygous regulatory loci. Such loci are enriched for stochastic switching, which is defined as random transitions between fully methylated and unmethylated states of DNA. The methylation imbalances at thousands of loci are explainable by different relative frequencies of the methylated and unmethylated states for the two alleles. Further analyses provided a unifying model that links sequence-dependent allelic imbalances of the epigenome, stochastic switching at gene regulatory loci, and disease-associated genetic variation.}, } @article {pmid30139912, year = {2018}, author = {Qi, X and Schmiege, P and Coutavas, E and Li, X}, title = {Two Patched molecules engage distinct sites on Hedgehog yielding a signaling-competent complex.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {}, doi = {10.1126/science.aas8843}, pmid = {30139912}, issn = {1095-9203}, support = {P01 HL020948/HL/NHLBI NIH HHS/United States ; }, mesh = {Calcium/chemistry/physiology ; Cryoelectron Microscopy ; Hedgehog Proteins/*chemistry/genetics/ultrastructure ; Humans ; Multiprotein Complexes/*chemistry/genetics/ultrastructure ; Palmitic Acid/chemistry ; Patched-1 Receptor/*chemistry/genetics/ultrastructure ; Protein Domains ; Signal Transduction ; }, abstract = {Aberrant Hedgehog (HH) signaling leads to various types of cancer and birth defects. N-terminally palmitoylated HH initiates signaling by binding its receptor Patched-1 (PTCH1). A recent 1:1 PTCH1-HH complex structure visualized a palmitate-mediated binding site on HH, which was inconsistent with previous studies that implied a distinct, calcium-mediated binding site for PTCH1 and HH co-receptors. Our 3.5-angstrom resolution cryo-electron microscopy structure of native Sonic Hedgehog (SHH-N) in complex with PTCH1 at a physiological calcium concentration reconciles these disparate findings and demonstrates that one SHH-N molecule engages both epitopes to bind two PTCH1 receptors in an asymmetric manner. Functional assays using PTCH1 or SHH-N mutants that disrupt the individual interfaces illustrate that simultaneous engagement of both interfaces is required for efficient signaling in cells.}, } @article {pmid30139911, year = {2018}, author = {Faria, NR and Kraemer, MUG and Hill, SC and Goes de Jesus, J and Aguiar, RS and Iani, FCM and Xavier, J and Quick, J and du Plessis, L and Dellicour, S and Thézé, J and Carvalho, RDO and Baele, G and Wu, CH and Silveira, PP and Arruda, MB and Pereira, MA and Pereira, GC and Lourenço, J and Obolski, U and Abade, L and Vasylyeva, TI and Giovanetti, M and Yi, D and Weiss, DJ and Wint, GRW and Shearer, FM and Funk, S and Nikolay, B and Fonseca, V and Adelino, TER and Oliveira, MAA and Silva, MVF and Sacchetto, L and Figueiredo, PO and Rezende, IM and Mello, EM and Said, RFC and Santos, DA and Ferraz, ML and Brito, MG and Santana, LF and Menezes, MT and Brindeiro, RM and Tanuri, A and Dos Santos, FCP and Cunha, MS and Nogueira, JS and Rocco, IM and da Costa, AC and Komninakis, SCV and Azevedo, V and Chieppe, AO and Araujo, ESM and Mendonça, MCL and Dos Santos, CC and Dos Santos, CD and Mares-Guia, AM and Nogueira, RMR and Sequeira, PC and Abreu, RG and Garcia, MHO and Abreu, AL and Okumoto, O and Kroon, EG and de Albuquerque, CFC and Lewandowski, K and Pullan, ST and Carroll, M and de Oliveira, T and Sabino, EC and Souza, RP and Suchard, MA and Lemey, P and Trindade, GS and Drumond, BP and Filippis, AMB and Loman, NJ and Cauchemez, S and Alcantara, LCJ and Pybus, OG}, title = {Genomic and epidemiological monitoring of yellow fever virus transmission potential.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {894-899}, doi = {10.1126/science.aat7115}, pmid = {30139911}, issn = {1095-9203}, support = {T32 HD040128/HD/NICHD NIH HHS/United States ; R01 LM010812/LM/NLM NIH HHS/United States ; R01 LM011965/LM/NLM NIH HHS/United States ; //European Research Council/International ; //Wellcome Trust/United Kingdom ; }, mesh = {Aedes/virology ; Age Factors ; Animals ; Brazil/epidemiology ; Disease Outbreaks/*prevention & control/statistics & numerical data ; *Epidemiological Monitoring ; Evolution, Molecular ; Genomics/*methods ; Humans ; Phylogeny ; Polymerase Chain Reaction ; Risk ; Sex Factors ; Spatio-Temporal Analysis ; Yellow Fever/epidemiology/*prevention & control/*transmission/virology ; Yellow fever virus/classification/genetics/*isolation & purification ; }, abstract = {The yellow fever virus (YFV) epidemic in Brazil is the largest in decades. The recent discovery of YFV in Brazilian Aedes species mosquitos highlights a need to monitor the risk of reestablishment of urban YFV transmission in the Americas. We use a suite of epidemiological, spatial, and genomic approaches to characterize YFV transmission. We show that the age and sex distribution of human cases is characteristic of sylvatic transmission. Analysis of YFV cases combined with genomes generated locally reveals an early phase of sylvatic YFV transmission and spatial expansion toward previously YFV-free areas, followed by a rise in viral spillover to humans in late 2016. Our results establish a framework for monitoring YFV transmission in real time that will contribute to a global strategy to eliminate future YFV epidemics.}, } @article {pmid30139874, year = {2018}, author = {Hellin, J}, title = {Inspiration from the outdoors.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {818}, doi = {10.1126/science.361.6404.818}, pmid = {30139874}, issn = {1095-9203}, } @article {pmid30139873, year = {2018}, author = {Saldivar, JC and Hamperl, S and Bocek, MJ and Chung, M and Bass, TE and Cisneros-Soberanis, F and Samejima, K and Xie, L and Paulson, JR and Earnshaw, WC and Cortez, D and Meyer, T and Cimprich, KA}, title = {An intrinsic S/G2 checkpoint enforced by ATR.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {806-810}, doi = {10.1126/science.aap9346}, pmid = {30139873}, issn = {1095-9203}, support = {R01 CA102729/CA/NCI NIH HHS/United States ; R35 GM127026/GM/NIGMS NIH HHS/United States ; P50 GM107615/GM/NIGMS NIH HHS/United States ; R01 GM119334/GM/NIGMS NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R01 ES016486/ES/NIEHS NIH HHS/United States ; }, mesh = {Antigens, Surface/metabolism ; Ataxia Telangiectasia Mutated Proteins/genetics/physiology ; Cyclin B1/antagonists & inhibitors/metabolism ; DNA Damage/genetics ; DNA Replication/genetics ; Forkhead Box Protein M1/metabolism ; G2 Phase/*genetics ; Gene Regulatory Networks ; HCT116 Cells ; Humans ; Mitosis/*genetics ; Phosphorylation ; S Phase/*genetics ; Telomerase ; }, abstract = {The cell cycle is strictly ordered to ensure faithful genome duplication and chromosome segregation. Control mechanisms establish this order by dictating when a cell transitions from one phase to the next. Much is known about the control of the G1/S, G2/M, and metaphase/anaphase transitions, but thus far, no control mechanism has been identified for the S/G2 transition. Here we show that cells transactivate the mitotic gene network as they exit the S phase through a CDK1 (cyclin-dependent kinase 1)-directed FOXM1 phosphorylation switch. During normal DNA replication, the checkpoint kinase ATR (ataxia-telangiectasia and Rad3-related) is activated by ETAA1 to block this switch until the S phase ends. ATR inhibition prematurely activates FOXM1, deregulating the S/G2 transition and leading to early mitosis, underreplicated DNA, and DNA damage. Thus, ATR couples DNA replication with mitosis and preserves genome integrity by enforcing an S/G2 checkpoint.}, } @article {pmid30139872, year = {2018}, author = {Pons-Salort, M and Grassly, NC}, title = {Serotype-specific immunity explains the incidence of diseases caused by human enteroviruses.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {800-803}, doi = {10.1126/science.aat6777}, pmid = {30139872}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Disease Outbreaks/*prevention & control ; Enterovirus/classification/*immunology/pathogenicity ; Enterovirus Infections/*epidemiology/immunology/*prevention & control ; Epidemiological Monitoring ; Humans ; Incidence ; Serogroup ; Serotyping ; Viral Vaccines/*immunology ; }, abstract = {Human enteroviruses are a major cause of neurological and other diseases. More than 100 serotypes are known that exhibit unexplained complex patterns of incidence, from regular cycles to more irregular patterns, and new emergences. Using 15 years of surveillance data from Japan (2000-2014) and a stochastic transmission model with accurate demography, we show that acquired serotype-specific immunity can explain the diverse patterns of 18 of the 20 most common serotypes (including Coxsackieviruses, Echoviruses, and Enterovirus-A71). The remaining two serotypes required a change in viral characteristics, including an increase in pathogenicity for Coxsackievirus-A6, which is consistent with its recent global rise in incidence. On the basis of our findings, we are able to predict outbreaks 2 years ahead of time (2015-2016). These results have implications for the impact of vaccines under development.}, } @article {pmid30139871, year = {2018}, author = {Li, X and Bamba, M and Yuan, N and Zhang, Q and Zhao, Y and Xiang, M and Xu, K and Jin, Z and Ren, W and Ma, G and Cao, S and Turchinovich, D and Kono, J}, title = {Observation of Dicke cooperativity in magnetic interactions.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {794-797}, doi = {10.1126/science.aat5162}, pmid = {30139871}, issn = {1095-9203}, abstract = {The interaction of N two-level atoms with a single-mode light field is an extensively studied many-body problem in quantum optics, first analyzed by Dicke in the context of superradiance. A characteristic of such systems is the cooperative enhancement of the coupling strength by a factor of N. In this study, we extended this cooperatively enhanced coupling to a solid-state system, demonstrating that it also occurs in a magnetic solid in the form of matter-matter interaction. Specifically, the exchange interaction of N paramagnetic erbium(III) (Er3+) spins with an iron(III) (Fe3+) magnon field in erbium orthoferrite (ErFeO3) exhibits a vacuum Rabi splitting whose magnitude is proportional to N. Our results provide a route for understanding, controlling, and predicting novel phases of condensed matter using concepts and tools available in quantum optics.}, } @article {pmid30139870, year = {2018}, author = {Gutiérrez, C and Walkup, D and Ghahari, F and Lewandowski, C and Rodriguez-Nieva, JF and Watanabe, K and Taniguchi, T and Levitov, LS and Zhitenev, NB and Stroscio, JA}, title = {Interaction-driven quantum Hall wedding cake-like structures in graphene quantum dots.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {789-794}, doi = {10.1126/science.aar2014}, pmid = {30139870}, issn = {1095-9203}, abstract = {Quantum-relativistic matter is ubiquitous in nature; however, it is notoriously difficult to probe. The ease with which external electric and magnetic fields can be introduced in graphene opens a door to creating a tabletop prototype of strongly confined relativistic matter. Here, through a detailed spectroscopic mapping, we directly visualize the interplay between spatial and magnetic confinement in a circular graphene resonator as atomic-like shell states condense into Landau levels. We directly observe the development of a "wedding cake"-like structure of concentric regions of compressible-incompressible quantum Hall states, a signature of electron interactions in the system. Solid-state experiments can, therefore, yield insights into the behavior of quantum-relativistic matter under extreme conditions.}, } @article {pmid30139869, year = {2018}, author = {Balajka, J and Hines, MA and DeBenedetti, WJI and Komora, M and Pavelec, J and Schmid, M and Diebold, U}, title = {High-affinity adsorption leads to molecularly ordered interfaces on TiO2 in air and solution.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {786-789}, doi = {10.1126/science.aat6752}, pmid = {30139869}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Researchers around the world have observed the formation of molecularly ordered structures of unknown origin on the surface of titanium dioxide (TiO2) photocatalysts exposed to air and solution. Using a combination of atomic-scale microscopy and spectroscopy, we show that TiO2 selectively adsorbs atmospheric carboxylic acids that are typically present in parts-per-billion concentrations while effectively repelling other adsorbates, such as alcohols, that are present in much higher concentrations. The high affinity of the surface for carboxylic acids is attributed to their bidentate binding. These self-assembled monolayers have the unusual property of being both hydrophobic and highly water-soluble, which may contribute to the self-cleaning properties of TiO2 This finding is relevant to TiO2 photocatalysis, because the self-assembled carboxylate monolayers block the undercoordinated surface cation sites typically implicated in photocatalysis.}, } @article {pmid30139868, year = {2018}, author = {Xia, C and Kwok, CY and Nazar, LF}, title = {A high-energy-density lithium-oxygen battery based on a reversible four-electron conversion to lithium oxide.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {777-781}, doi = {10.1126/science.aas9343}, pmid = {30139868}, issn = {1095-9203}, abstract = {Lithium-oxygen (Li-O2) batteries have attracted much attention owing to the high theoretical energy density afforded by the two-electron reduction of O2 to lithium peroxide (Li2O2). We report an inorganic-electrolyte Li-O2 cell that cycles at an elevated temperature via highly reversible four-electron redox to form crystalline lithium oxide (Li2O). It relies on a bifunctional metal oxide host that catalyzes O-O bond cleavage on discharge, yielding a high capacity of 11 milliampere-hours per square centimeter, and O2 evolution on charge with very low overpotential. Online mass spectrometry and chemical quantification confirm that oxidation of Li2O involves transfer of exactly 4 e-/O2 This work shows that Li-O2 electrochemistry is not intrinsically limited once problems of electrolyte, superoxide, and cathode host are overcome and that coulombic efficiency close to 100% can be achieved.}, } @article {pmid30139867, year = {2018}, author = {}, title = {Quality mentoring.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {762}, doi = {10.1126/science.361.6404.762-b}, pmid = {30139867}, issn = {1095-9203}, mesh = {Interpersonal Relations ; *Mentoring ; *Mentors ; }, } @article {pmid30139866, year = {2018}, author = {Schlick-Steiner, BC and Arthofer, W and Steiner, FM}, title = {Anticipating data-induced bias.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {762}, doi = {10.1126/science.aau9816}, pmid = {30139866}, issn = {1095-9203}, mesh = {*Bias ; }, } @article {pmid30139865, year = {2018}, author = {Mejlgaard, N and Woolley, R and Bloch, C and Bührer, S and Griessler, E and Jäger, A and Lindner, R and Madsen, EB and Maier, F and Meijer, I and Peter, V and Stilgoe, J and Wuketich, M}, title = {Europe's plans for responsible science.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {761-762}, doi = {10.1126/science.aav0400}, pmid = {30139865}, issn = {1095-9203}, } @article {pmid30139864, year = {2018}, author = {Tang, GY and Parekh, J}, title = {Side effects of addiction treatment.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {761}, doi = {10.1126/science.aau6548}, pmid = {30139864}, issn = {1095-9203}, mesh = {*Behavior, Addictive ; *Drug-Related Side Effects and Adverse Reactions ; Humans ; }, } @article {pmid30139863, year = {2018}, author = {Feng, S and Lunger, JR and Johnson, JA and Shao-Horn, Y}, title = {Hot lithium-oxygen batteries charge ahead.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {758}, doi = {10.1126/science.aau4792}, pmid = {30139863}, issn = {1095-9203}, mesh = {Electric Power Supplies ; Electrodes ; *Lithium ; *Oxygen ; }, } @article {pmid30139862, year = {2018}, author = {Pasparakis, M and Kelliher, M}, title = {Connecting immune deficiency and inflammation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {756-757}, doi = {10.1126/science.aau6962}, pmid = {30139862}, issn = {1095-9203}, mesh = {Humans ; *Immunologic Deficiency Syndromes ; *Inflammation ; }, } @article {pmid30139861, year = {2018}, author = {Nikolay, B and Cauchemez, S}, title = {Enterovirus outbreak dynamics.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {755-756}, doi = {10.1126/science.aau6932}, pmid = {30139861}, issn = {1095-9203}, mesh = {Disease Outbreaks ; *Enterovirus ; Enterovirus Infections/*epidemiology ; Humans ; }, } @article {pmid30139860, year = {2018}, author = {Thomas, JL}, title = {Orchestrating cortical brain development.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {754-755}, doi = {10.1126/science.aau7155}, pmid = {30139860}, issn = {1095-9203}, mesh = {*Brain ; Cerebral Cortex ; Magnetic Resonance Imaging ; *Neurogenesis ; }, } @article {pmid30139859, year = {2018}, author = {Park, JY}, title = {How titanium dioxide cleans itself.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {753}, doi = {10.1126/science.aau6016}, pmid = {30139859}, issn = {1095-9203}, } @article {pmid30139858, year = {2018}, author = {Taddeo, M and Floridi, L}, title = {How AI can be a force for good.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {751-752}, doi = {10.1126/science.aat5991}, pmid = {30139858}, issn = {1095-9203}, mesh = {Artificial Intelligence/*ethics ; Decision Making/*ethics ; Human Rights ; Humans ; }, } @article {pmid30139857, year = {2018}, author = {Grafton, RQ and Williams, J and Perry, CJ and Molle, F and Ringler, C and Steduto, P and Udall, B and Wheeler, SA and Wang, Y and Garrick, D and Allen, RG}, title = {The paradox of irrigation efficiency.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {748-750}, doi = {10.1126/science.aat9314}, pmid = {30139857}, issn = {1095-9203}, mesh = {Agricultural Irrigation/*methods ; *Crops, Agricultural ; Drinking ; Policy ; }, } @article {pmid30139856, year = {2018}, author = {Wadman, M}, title = {Daring to hope.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {742-746}, doi = {10.1126/science.361.6404.742}, pmid = {30139856}, issn = {1095-9203}, mesh = {Animals ; Clinical Trials as Topic ; DNA, Antisense/administration & dosage/*therapeutic use ; Humans ; Huntingtin Protein/*antagonists & inhibitors/chemistry/*genetics ; Huntington Disease/*drug therapy/genetics ; Mutation ; }, } @article {pmid30139855, year = {2018}, author = {Normile, D}, title = {Arrival of deadly pig disease could spell disaster for China.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {741}, doi = {10.1126/science.361.6404.741}, pmid = {30139855}, issn = {1095-9203}, mesh = {African Swine Fever/*epidemiology/*prevention & control/virology ; Animals ; Asfarviridae/classification/genetics/isolation & purification ; China/epidemiology ; Disease Outbreaks/*prevention & control ; Swine ; }, } @article {pmid30139854, year = {2018}, author = {Cohen, J}, title = {Monthly shots may replace daily anti-HIV pills.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {740}, doi = {10.1126/science.361.6404.740}, pmid = {30139854}, issn = {1095-9203}, mesh = {Anti-HIV Agents/*administration & dosage ; Clinical Trials as Topic ; Delayed-Action Preparations ; Drug Administration Schedule ; HIV Infections/*prevention & control/*transmission ; Humans ; Injections ; Time Factors ; }, } @article {pmid30139853, year = {2018}, author = {Voosen, P}, title = {Sticky glaciers slowed tempo of ice ages.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {739}, doi = {10.1126/science.361.6404.739}, pmid = {30139853}, issn = {1095-9203}, } @article {pmid30139852, year = {2018}, author = {Kintisch, E}, title = {Project lifts the veil on life in the ocean's twilight zone.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {738}, doi = {10.1126/science.361.6404.738}, pmid = {30139852}, issn = {1095-9203}, mesh = {Animals ; *Aquatic Organisms ; *Biodiversity ; Oceans and Seas ; }, } @article {pmid30139851, year = {2018}, author = {Vogel, G}, title = {Ancient DNA reveals tryst between extinct human species.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {737}, doi = {10.1126/science.361.6404.737}, pmid = {30139851}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Bone and Bones ; *DNA, Ancient ; *Extinction, Biological ; Fathers/history ; Female ; History, Ancient ; Humans ; Mothers/history ; Neanderthals/*genetics ; Women/*history ; }, } @article {pmid30139850, year = {2018}, author = {Hand, E}, title = {Interplanetary small satellites come of age.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {736-737}, doi = {10.1126/science.361.6404.736}, pmid = {30139850}, issn = {1095-9203}, } @article {pmid30139849, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {734-735}, doi = {10.1126/science.361.6404.734}, pmid = {30139849}, issn = {1095-9203}, } @article {pmid30139848, year = {2018}, author = {Boyle, K and Kotchen, M}, title = {Retreat on economics at the EPA.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {729}, doi = {10.1126/science.aav0896}, pmid = {30139848}, issn = {1095-9203}, mesh = {Conservation of Natural Resources/*economics ; Economics ; United States ; United States Environmental Protection Agency/*economics ; }, } @article {pmid30139847, year = {2018}, author = {Bloom, DE and Khoury, A and Subbaraman, R}, title = {The promise and peril of universal health care.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {}, doi = {10.1126/science.aat9644}, pmid = {30139847}, issn = {1095-9203}, support = {P30 AG024409/AG/NIA NIH HHS/United States ; }, mesh = {Delivery of Health Care/*economics ; *Global Health ; Humans ; *Population Health ; United Nations ; Universal Health Insurance/*trends ; World Health Organization ; }, abstract = {Universal health care (UHC) is garnering growing support throughout the world, a reflection of social and economic progress and of the recognition that population health is both an indicator and an instrument of national development. Substantial human and financial resources will be required to achieve UHC in any of the various ways it has been conceived and defined. Progress toward achieving UHC will be aided by new technologies, a willingness to shift medical tasks from highly trained to appropriately well-trained personnel, a judicious balance between the quantity and quality of health care services, and resource allocation decisions that acknowledge the important role of public health interventions and nonmedical influences on population health.}, } @article {pmid30139846, year = {2018}, author = {Kroodsma, DA and Mayorga, J and Hochberg, T and Miller, NA and Boerder, K and Ferretti, F and Wilson, A and Bergman, B and White, TD and Block, BA and Woods, P and Sullivan, B and Costello, C and Worm, B}, title = {Response to Comment on "Tracking the global footprint of fisheries".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {}, doi = {10.1126/science.aat7789}, pmid = {30139846}, issn = {1095-9203}, mesh = {Animals ; Conservation of Natural Resources ; Ecosystem ; *Fisheries ; *Fishes ; Human Activities ; Humans ; }, abstract = {Amoroso et al demonstrate the power of our data by estimating the high-resolution trawling footprint on seafloor habitat. Yet we argue that a coarser grid is required to understand full ecosystem impacts. Vessel tracking data allow us to estimate the footprint of human activities across a variety of scales, and the proper scale depends on the specific impact being investigated.}, } @article {pmid30139845, year = {2018}, author = {Amoroso, RO and Parma, AM and Pitcher, CR and McConnaughey, RA and Jennings, S}, title = {Comment on "Tracking the global footprint of fisheries".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {}, doi = {10.1126/science.aat6713}, pmid = {30139845}, issn = {1095-9203}, mesh = {*Agriculture ; Conservation of Natural Resources ; *Fisheries ; Fishes ; }, abstract = {Kroodsma et al (Reports, 23 February 2018, p. 904) mapped the global footprint of fisheries. Their estimates of footprint and resulting contrasts between the scale of fishing and agriculture are an artifact of the spatial scale of analysis. Reanalyses of their global (all vessels) and regional (trawling) data at higher resolution reduced footprint estimates by factors of >10 and >5, respectively.}, } @article {pmid30139844, year = {2018}, author = {Segarra, M and Aburto, MR and Cop, F and Llaó-Cid, C and Härtl, R and Damm, M and Bethani, I and Parrilla, M and Husainie, D and Schänzer, A and Schlierbach, H and Acker, T and Mohr, L and Torres-Masjoan, L and Ritter, M and Acker-Palmer, A}, title = {Endothelial Dab1 signaling orchestrates neuro-glia-vessel communication in the central nervous system.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {}, doi = {10.1126/science.aao2861}, pmid = {30139844}, issn = {1095-9203}, mesh = {Animals ; Blood-Brain Barrier/cytology/physiology ; Cell Adhesion Molecules, Neuronal/genetics/metabolism ; *Cell Communication ; Cell Movement ; Cerebral Cortex/*blood supply ; Endothelium, Vascular/metabolism/*physiology ; Extracellular Matrix Proteins/genetics/metabolism ; Female ; Gene Deletion ; Integrin beta1/metabolism ; LDL-Receptor Related Proteins/genetics/metabolism ; Laminin/metabolism ; Male ; Mice ; Mice, Knockout ; *Neovascularization, Physiologic ; Nerve Tissue Proteins/genetics/*metabolism ; Neuroglia/cytology/metabolism/*physiology ; Neurons/metabolism/*physiology ; Retinal Vessels/cytology/*physiology ; Serine Endopeptidases/genetics/metabolism ; Signal Transduction ; }, abstract = {The architecture of the neurovascular unit (NVU) is controlled by the communication of neurons, glia, and vascular cells. We found that the neuronal guidance cue reelin possesses proangiogenic activities that ensure the communication of endothelial cells (ECs) with the glia to control neuronal migration and the establishment of the blood-brain barrier in the mouse brain. Apolipoprotein E receptor 2 (ApoER2) and Disabled1 (Dab1) expressed in ECs are required for vascularization of the retina and the cerebral cortex. Deletion of Dab1 in ECs leads to a reduced secretion of laminin-α4 and decreased activation of integrin-β1 in glial cells, which in turn control neuronal migration and barrier properties of the NVU. Thus, reelin signaling in the endothelium is an instructive and integrative cue essential for neuro-glia-vascular communication.}, } @article {pmid30139843, year = {2018}, author = {Vemu, A and Szczesna, E and Zehr, EA and Spector, JO and Grigorieff, N and Deaconescu, AM and Roll-Mecak, A}, title = {Severing enzymes amplify microtubule arrays through lattice GTP-tubulin incorporation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {}, doi = {10.1126/science.aau1504}, pmid = {30139843}, issn = {1095-9203}, support = {R01 GM121975/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans ; Drosophila melanogaster ; Guanosine Triphosphate/*metabolism ; Humans ; Katanin/*metabolism ; Microscopy, Electron ; Microscopy, Fluorescence ; Microtubules/*metabolism/*ultrastructure ; Single Molecule Imaging ; Spastin/*metabolism ; Tubulin/*metabolism ; }, abstract = {Spastin and katanin sever and destabilize microtubules. Paradoxically, despite their destructive activity they increase microtubule mass in vivo. We combined single-molecule total internal reflection fluorescence microscopy and electron microscopy to show that the elemental step in microtubule severing is the generation of nanoscale damage throughout the microtubule by active extraction of tubulin heterodimers. These damage sites are repaired spontaneously by guanosine triphosphate (GTP)-tubulin incorporation, which rejuvenates and stabilizes the microtubule shaft. Consequently, spastin and katanin increase microtubule rescue rates. Furthermore, newly severed ends emerge with a high density of GTP-tubulin that protects them against depolymerization. The stabilization of the newly severed plus ends and the higher rescue frequency synergize to amplify microtubule number and mass. Thus, severing enzymes regulate microtubule architecture and dynamics by promoting GTP-tubulin incorporation within the microtubule shaft.}, } @article {pmid30139842, year = {2018}, author = {Altounian, V and Stampfli, P}, title = {Cover stories: Making the graphene quasicrystals cover.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {}, doi = {10.1126/science.aav1395}, pmid = {30139842}, issn = {1095-9203}, } @article {pmid30139641, year = {2018}, author = {de Los Campos, G and Vazquez, AI and Hsu, S and Lello, L}, title = {Complex-Trait Prediction in the Era of Big Data.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {10}, pages = {746-754}, pmid = {30139641}, issn = {0168-9525}, support = {R01 GM099992/GM/NIGMS NIH HHS/United States ; R01 GM101219/GM/NIGMS NIH HHS/United States ; }, abstract = {Accurate prediction of complex traits requires using a large number of DNA variants. Advances in statistical and machine learning methodology enable the identification of complex patterns in high-dimensional settings. However, training these highly parameterized methods requires very large data sets. Until recently, such data sets were not available. But the situation is changing rapidly as very large biomedical data sets comprising individual genotype-phenotype data for hundreds of thousands of individuals become available in public and private domains. We argue that the convergence of advances in methodology and the advent of Big Genomic Data will enable unprecedented improvements in complex-trait prediction; we review theory and evidence supporting our claim and discuss challenges and opportunities that Big Data will bring to complex-trait prediction.}, } @article {pmid30139554, year = {2018}, author = {Alba, DM and Delson, E and Morales, J and Montoya, P and Romero, G}, title = {Macaque remains from the early Pliocene of the Iberian Peninsula.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {141-147}, doi = {10.1016/j.jhevol.2018.07.005}, pmid = {30139554}, issn = {1095-8606}, abstract = {Macaques dispersed out of Africa into Eurasia in the framework of a broader intercontinental faunal exchange that coincided in time with the sea level drop associated with the Messinian Salinity Crisis. They are first recorded in Europe (Italy and Spain) by the latest Miocene, being subsequently recorded all over Europe, albeit sparsely, throughout the Pliocene and Pleistocene. These fossil European macaques are attributed to several (sub)species of the extant Barbary macaque (Macaca sylvanus). In Iberia, fossil macaques are best documented by Macaca sylvanus florentina from various Early Pleistocene sites, whereas their published Pliocene record is very scarce. Here we report the oldest post-Messinian occurrence of macaques in the Iberian Peninsula, based on the description and metrical comparisons of two upper teeth (a male canine and a third molar of two different individuals) from the early Pliocene (MN14, 5.0-4.9 Ma) site of Puerto de la Cadena (Murcia, SE Spain). The male C1 is fully comparable in morphology with those of extant and fossil M. sylvanus, and larger than those of Mesopithecus. The M3, in turn, displays the typical papionin morphology that characterizes the dentally-conservative genus Macaca-thereby discounting an alternate assignment to either the extinct colobine monkey Mesopithecus or the more dentally-derived papionin Theropithecus. Dental size and proportions of the M3 further support an attribution to an extinct subspecies of M. sylvanus instead of the larger papionin Paradolichopithecus. Mostly on biochronologic grounds, the two macaque teeth from Puerto de la Cadena are here assigned to Macaca sylvanus cf. prisca, albeit tentatively, given the lack of clear-cut criteria to distinguish this subspecies from the younger Macaca sylvanus florentina. The described material represents the oldest well-dated Pliocene record of macaques in Iberia, predating the record of Paradolichopithecus by almost 1.5 million years.}, } @article {pmid30139366, year = {2018}, author = {Brémault-Phillips, S and Pike, A and Charles, L and Roduta-Roberts, M and Mitra, A and Friesen, S and Moulton, L and Parmar, J}, title = {Facilitating implementation of the Decision-Making Capacity Assessment (DMCA) Model: senior leadership perspectives on the use of the National Implementation Research Network (NIRN) Model and frameworks.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {607}, pmid = {30139366}, issn = {1756-0500}, support = {1596//Covenant Health Network of Excellence in Seniors' Health and Wellness/ ; }, mesh = {Alberta ; Chronic Disease ; *Decision Making ; Dementia ; Focus Groups ; Humans ; *Leadership ; *Legal Guardians ; *Mental Competency ; Models, Theoretical ; Research ; }, abstract = {OBJECTIVE: Dementia and other chronic conditions can compromise a person's ability to make independent personal and financial decisions. In the wake of an ageing population and rising incidence of chronic conditions, the number of persons who may require Decision-Making Capacity Assessments (DMCAs) is likely to increase. Legislation (e.g., Trusteeship, Guardianship, Medical Assistance in Dying) also necessitates that DMCAs adhere to legislative requirements and principles. An intentional, explicit and systematic means of implementing standardized DMCA best-practices is advisable. This single exploratory case-study examined the perspectives of senior leaders and clinical experts regarding the utility of using the National Implementation Research Network (NIRN) Model to facilitate implementation, spread and sustainability of a DMCA Model. Participants learned about the NIRN Model and discussed its application during working and focus groups, all of which were audio-recorded, transcribed, and analyzed using thematic analysis.

RESULTS: Participants found that the NIRN Model aligned well with the DMCA Model, and offered utility to support implementation, spread and sustainability of DMCA best-practices. Participants also noted barriers related to its language, inability to capture personal change, resource requirements, and complexity. It was recommended that a NIRN-informed DMCA-specific implementation framework and toolkit be developed and NIRN-champions be available to guide implementation.}, } @article {pmid30139352, year = {2018}, author = {Li, T and Qu, J and Wang, Y and Chang, L and He, K and Guo, D and Zhang, X and Xu, S and Xue, J}, title = {Genetic characterization of inbred lines from Shaan A and B groups for identifying loci associated with maize grain yield.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {63}, pmid = {30139352}, issn = {1471-2156}, support = {2017ZDXCL-NY-02-04//Innovation Project of Science and Technology of Shaanxi Province/ ; }, abstract = {BACKGROUND: Increasing grain yield is a primary objective of maize breeding. Dissecting the genetic architecture of grain yield furthers genetic improvements to increase yield. Presented here is an association panel composed of 126 maize inbreds (AM126), which were genotyped by the genotyping-by-sequencing (tGBS) method. We performed genetic characterization and association analysis related to grain yield in the association panel.

RESULTS: In total, 46,046 SNPs with a minor allele frequency (MAF) ≥0.01 were used to assess genetic diversity and kinship in AM126. The results showed that the average MAF and polymorphism information content (PIC) were 0.164 and 0.198, respectively. The Shaan B group, with 11,284 unique SNPs, exhibited greater genetic diversity than did the Shaan A group, with 2644 SNPs. The 61.82% kinship coefficient in AM126 was equal to 0, and only 0.15% of that percentage was greater than 0.7. A total of 31,983 SNPs with MAF ≥0.05 were used to characterize population structure, LD decay and association mapping. Population structure analysis suggested that AM126 can be divided into 6 subgroups, which is consistent with breeding experience and pedigree information. The LD decay distance in AM126 was 150 kb. A total of 51 significant SNPs associated with grain yield were identified at P < 1 × 10- 3 across two environments (Yangling and Yulin). Among those SNPs, two loci displayed overlapping regions in the two environments. Finally, 30 candidate genes were found to be associated with grain yield.

CONCLUSIONS: These results contribute to the genetic characterization of this breeding population, which serves as a reference for hybrid breeding and population improvement, and demonstrate the genetic architecture of maize grain yield, potentially facilitating genetic improvement.}, } @article {pmid30139335, year = {2018}, author = {Visser, EA and Wegrzyn, JL and Myburg, AA and Naidoo, S}, title = {Defence transcriptome assembly and pathogenesis related gene family analysis in Pinus tecunumanii (low elevation).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {632}, pmid = {30139335}, issn = {1471-2164}, support = {97892//National Research Foundation/ ; 86936//National Research Foundation/ ; 97911//National Research Foundation/ ; 96413//Technology and Human Resources for Industry Programme (THRIP)/ ; }, mesh = {Fusarium/physiology ; *Gene Expression Profiling/standards ; Molecular Sequence Annotation ; Pinus/*genetics/*microbiology ; Plant Diseases/*genetics/*microbiology ; Reference Standards ; }, abstract = {BACKGROUND: Fusarium circinatum is a pressing threat to the cultivation of many economically important pine tree species. Efforts to develop effective disease management strategies can be aided by investigating the molecular mechanisms involved in the host-pathogen interaction between F. circinatum and pine species. Pinus tecunumanii and Pinus patula are two closely related tropical pine species that differ widely in their resistance to F. circinatum challenge, being resistant and susceptible respectively, providing the potential for a useful pathosystem to investigate the molecular responses underlying resistance to F. circinatum. However, no genomic resources are available for P. tecunumanii. Pathogenesis-related proteins are classes of proteins that play important roles in plant-microbe interactions, e.g. chitinases; proteins that break down the major structural component of fungal cell walls. Generating a reference sequence for P. tecunumanii and characterizing pathogenesis related gene families in these two pine species is an important step towards unravelling the pine-F. circinatum interaction.

RESULTS: Eight reference based and 12 de novo assembled transcriptomes were produced, for juvenile shoot tissue from both species. EvidentialGene pipeline redundancy reduction, expression filtering, protein clustering and taxonomic filtering produced a 50 Mb shoot transcriptome consisting of 28,621 contigs for P. tecunumanii and a 72 Mb shoot transcriptome consisting of 52,735 contigs for P. patula. Predicted protein sequences encoded by the assembled transcriptomes were clustered with reference proteomes from 92 other species to identify pathogenesis related gene families in P. patula, P. tecunumanii and other pine species.

CONCLUSIONS: The P. tecunumanii transcriptome is the first gene catalogue for the species, representing an important resource for studying resistance to the pitch canker pathogen, F. circinatum. This study also constitutes, to our knowledge, the largest index of gymnosperm PR-genes to date.}, } @article {pmid30139328, year = {2018}, author = {Wang, J and Zhao, Y and Zhou, X and Hiebert, SW and Liu, Q and Shyr, Y}, title = {Nascent RNA sequencing analysis provides insights into enhancer-mediated gene regulation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {633}, pmid = {30139328}, issn = {1471-2164}, support = {U54 CA217450/CA/NCI NIH HHS/United States ; P50 CA095103/CA/NCI NIH HHS/United States ; U01 CA163056/CA/NCI NIH HHS/United States ; U24 CA163056/CA/NCI NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; 5U01 CA163056-05//National Cancer Institute (US)/ ; }, mesh = {Animals ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation/*genetics ; Histone Deacetylases/metabolism ; Humans ; Liver/metabolism ; Mice ; Promoter Regions, Genetic/genetics ; *Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Enhancers are distal cis-regulatory elements that control gene expression. Despite an increasing appreciation of the importance of enhancers in cellular function and disease, our knowledge of enhancer-regulated transcription is very limited. Nascent RNA sequencing technologies, such as global nuclear run-on sequencing (GRO-seq) and precision run-on sequencing (PRO-seq), not only provide a direct and reliable measurement of enhancer activity, but also allow for quantifying transcription of enhancers and target genes simultaneously, making these technologies extremely useful for exploring enhancer-mediated regulation.

RESULTS: Nascent RNA sequencing analysis (NRSA) provides a comprehensive view of enhancer-mediated gene regulation. NRSA not only outperforms existing methods for enhancer identification, but also enables annotation and quantification of active enhancers, and prediction of their target genes. Furthermore, NRSA identifies functionally important enhancers by integrating 1) nascent transcriptional changes in enhancers and their target genes and 2) binding profiles from regulator(s) of interest. Applied to wildtype and histone deacetylase 3 (Hdac3) knockout mouse livers, NRSA showed that HDAC3 regulates RNA polymerase recruitment through both proximal (promoter) and distal (enhancer) regulatory elements. Integrating ChIP-seq with PRO-seq data, NRSA prioritized enhancers based on their potential contribution to mediating HDAC3 regulation.

CONCLUSIONS: NRSA will greatly facilitate the usage of nascent RNA sequencing techniques and accelerate the study of enhancer-mediated regulation.}, } @article {pmid30139327, year = {2018}, author = {Wang, S and Luo, Z and Zhang, Y and Yuan, D and Ge, W and Wang, X}, title = {The inconsistent regulation of HOXC13 on different keratins and the regulation mechanism on HOXC13 in cashmere goat (Capra hircus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {630}, pmid = {30139327}, issn = {1471-2164}, support = {31472068//National Natural Science Foundation of China/ ; 31772573//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Goats ; HEK293 Cells ; Homeodomain Proteins/chemistry/genetics/*metabolism ; Humans ; Keratins/genetics/*metabolism ; Mutation ; Promoter Regions, Genetic/genetics ; Protein Domains ; Wool/metabolism ; }, abstract = {BACKGROUND: During hair growth, cortical cells emerging from the proliferative follicle bulb rapidly undergo a differentiation program and synthesize large amounts of hair keratin proteins. In this process, HOXC13 is one critical regulatory factor, proved by the hair defects in HOXC13 mutant mice and HOXC13 mutant patients. However, inconsistent conclusions were drawn from previous researches regarding the regulation of HOXC13 on different keratins. Whether HOXC13 has extensive and unified regulatory role on these numerous keratins is unclear.

RESULTS: In this study, firstly, RNA-seq was performed to reveal the molecular mechanism of cashmere cycle including anagen and telogen. Subsequently, combining the sequencing with qRT-PCR and immunofluorescent staining results, we found that HOXC13 showed similar expression pattern with a large proportion of keratins except for KRT1 and KRT2, which were higher in anagen compared with telogen. Then, the regulatory role of HOXC13 on different keratins was investigated using dual-luciferase reporter system and keratin promoter-GFP system by overexpressing HOXC13 in HEK 293 T cells and dermal papilla cells. Our results demonstrated that HOXC13 up-regulated the promoter activity of KRT84 and KRT38, while down-regulated the promoter activity of KRT1 and KRT2, which suggested HOXC13 had an ambivalent effect on the promoters of different KRTs. Furtherly, the regulation on HOXC13 itself was investigated. At transcriptional level, the binding sites of HOXC13 and LEF1 were found in the promoter of HOXC13. Then, through transfecting corresponding overexpression vector and dual-luciferase reporter system into dermal papilla cells, the negative-feedback regulation of HOXC13 itself and positive regulation of LEF1 on HOXC13 promoter were revealed. In addition, melatonin could significantly increase the promoter activity of HOXC13 under the concentration of 10 μM and 25 μM by adding exogenous melatonin into dermal papilla cells. At post-transcriptional level, we investigated whether chi-miR-200a could target HOXC13 through dual-luciferase reporter system. At epigenetic level, we investigated the methylation level of HOXC13 promoter at different stages including anagen, telogen and 60d of embryonic period. As a result, miR-200a and methylation were not regulatory factors of HOXC13. Interestingly, we found two SNPs (c.812A > G and c.929A > C) in the homeodomain of HOXC13 that could deprive the regulatory function of HOXC13 on keratins without changing its protein expression.

CONCLUSION: HOXC13 had an inconsistent effect on the promoters of different keratins. Two SNPs (c.812A > G and c.929A > C) in the homeodomain of HOXC13 deprived its function on keratin regulation. Besides, the negative-feedback regulation by HOXC13 itself and positive regulation by LEF1 and melatonin on HOXC13 promoter were revealed. This study will enrich the function of HOXC13 on keratin regulation and contribute to understand the mechanism of hair follicle differentiation.}, } @article {pmid30139326, year = {2018}, author = {Wu, F and Liu, Y and Wu, Q and Li, D and Zhang, L and Wu, X and Wang, R and Zhang, D and Gao, S and Li, W}, title = {Long non-coding RNAs potentially function synergistically in the cellular reprogramming of SCNT embryos.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {631}, pmid = {30139326}, issn = {1471-2164}, support = {31372273//National Natural Science Foundation of China/ ; 31501906//National Natural Science Foundation of China/ ; gxyqZD201619//Key Grant of the Key projects of the outstanding young talents in Colleges and Universities of Anhui Province/ ; 2018HXXM22//the research project of Fuyang Normal University/ ; }, mesh = {Animals ; *Cellular Reprogramming ; Embryo, Mammalian/*cytology ; Fertilization ; Mice ; *Nuclear Transfer Techniques ; RNA, Long Noncoding/*genetics ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs), a type of epigenetic regulator, are thought to play important roles in embryonic development in mice, and several developmental defects are associated with epigenetic modification disorders. The most dramatic epigenetic reprogramming event occurs during somatic cell nuclear transfer (SCNT) when the expression profile of a differentiated cell is abolished, and a newly embryo-specific expression profile is established. However, the molecular mechanism underlying somatic reprogramming remains unclear, and the dynamics and functions of lncRNAs in this process have not yet been illustrated, resulting in inefficient reprogramming.

RESULTS: In this study, 63 single-cell RNA-seq libraries were first generated and sequenced. A total of 7009 mouse polyadenylation lncRNAs (including 5204 novel lncRNAs) were obtained, and a comprehensive analysis of in vivo and SCNT mouse pre-implantation embryo lncRNAs was further performed based on our single-cell RNA sequencing data. Expression profile analysis revealed that lncRNAs were expressed in a developmental stage-specific manner during mouse early-stage embryonic development, whereas a more temporal and spatially specific expression pattern was identified in mouse SCNT embryos with changes in the state of chromatin during somatic cell reprogramming, leading to incomplete zygotic genome activation, oocyte to embryo transition and 2-cell to 4-cell transition. No obvious differences between other stages and mouse NTC or NTM embryos at the same stage were observed. Gene oncology (GO) enrichment analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis and weighted gene co-expression network analysis (WGCNA) of lncRNAs and their association with known protein-coding genes suggested that several lncRNAs and their associated with known protein-coding genes might be involved in mouse embryonic development and cell reprogramming.

CONCLUSIONS: This is a novel report on the expression landscapes of lncRNAs of mouse NT embryos by scRNA-seq analysis. This study will provide insight into the molecular mechanism underlying the involvement of lncRNAs in mouse pre-implantation embryonic development and epigenetic reprogramming in mammalian species after SCNT-based cloning.}, } @article {pmid30138937, year = {2018}, author = {}, title = {The 38th Annual Meeting of the J.B. Johnston Club for Evolutionary Neuroscience and the 30th Annual Karger Workshop in Evolutionary Neuroscience: Abstracts.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {4}, pages = {252-260}, doi = {10.1159/000492046}, pmid = {30138937}, issn = {1421-9743}, } @article {pmid30138723, year = {2018}, author = {Covarrubias, PC and Moya-Beltrán, A and Atavales, J and Moya-Flores, F and Tapia, PS and Acuña, LG and Spinelli, S and Quatrini, R}, title = {Occurrence, integrity and functionality of AcaML1-like viruses infecting extreme acidophiles of the Acidithiobacillus species complex.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {628-637}, doi = {10.1016/j.resmic.2018.07.005}, pmid = {30138723}, issn = {1769-7123}, mesh = {Acidithiobacillus/genetics/metabolism/*virology ; Bacterial Proteins/genetics/metabolism ; Bacteriophages/genetics/isolation & purification/*physiology ; Proviruses/genetics/isolation & purification/*physiology ; Viral Proteins/genetics/metabolism ; Virus Integration ; }, abstract = {General knowledge on the diversity and biology of microbial viruses infecting bacterial hosts from extreme acidic environments lags behind most other econiches. In this study, we analyse the AcaML1 virus occurrence in the taxon, its genetic composition and infective behaviour under standard acidic and SOS-inducing conditions to assess its integrity and functionality. Occurrence analysis in sequenced acidithiobacilli showed that AcaML1-like proviruses are confined to the mesothermophiles Acidithiobacillus caldus and Thermithiobacillus tepidarius. Among A. caldus strains and isolates this provirus had a modest prevalence (30%). Comparative genomic analysis revealed a significant conservation with the T. tepidarius AcaML1-like provirus, excepting the tail genes, and a high conservation of the virus across strains of the A. caldus species. Such conservation extends from the modules architecture to the gene level, suggesting that organization and composition of these viruses are preserved for functional reasons. Accordingly, the AcaML1 proviruses were demonstrated to excise from their host genomes under DNA-damaging conditions triggering the SOS-response and to produce DNA-containing VLPs. Despite this fact, under the conditions evaluated (acidic) the VLPs obtained from A. caldus ATCC 51756 could not produce productive infections of a candidate sensitive strain (#6) nor trigger it lysis.}, } @article {pmid30138722, year = {2018}, author = {Schwabe, R and Anke, MK and Szymańska, K and Wiche, O and Tischler, D}, title = {Analysis of desferrioxamine-like siderophores and their capability to selectively bind metals and metalloids: development of a robust analytical RP-HPLC method.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {598-607}, doi = {10.1016/j.resmic.2018.08.002}, pmid = {30138722}, issn = {1769-7123}, mesh = {Chromatography, High Pressure Liquid/methods ; Chromatography, Reverse-Phase/*methods ; Deferoxamine/*analysis/metabolism ; Gordonia Bacterium/chemistry/*metabolism ; Metalloids/*analysis/metabolism ; Metals/*analysis/metabolism ; Siderophores/*analysis/metabolism ; }, abstract = {The Actinobacterium Gordonia rubripertincta CWB2 (DSM 46758) produces hydroxamate-type siderophores (188 mg L-1) under iron limitation. Analytical reversed-phase HPLC allowed determining a single peak of ferric iron chelating compounds from culture broth which was confirmed by the Fe-CAS assay. Elution profile and its absorbance spectrum were similar to those of commercial (des)ferrioxamine B which was used as reference compound. This confirms previously made assumptions and shows for the first time that the genus Gordonia produces desferrioxamine-like siderophores. The reversed-phase HPLC protocol was optimized to separate metal-free and -loaded oxamines. This allowed to determine siderophore concentrations in solutions as well as metal affinity. The metal loading of oxamines was confirmed by ICP-MS. As a result, it was demonstrated that desferrioxamine prefers trivalent metal ions (Fe3+ > Ga3+ > V3+ > Al3+) over divalent ones. In addition, we aimed to show the applicability of the newly established reversed-phase HPLC protocol and to increase the re-usability of desferrioxamines as metal chelators by immobilization on mesocellular silica foam carriers. The siderophores obtained from strain CWB2 and commercial desferrioxamine B were successfully linked to the carrier with a high yield (up to 95%) which was verified by the HPLC method. Metal binding studies demonstrated that metals can be bound to non-immobilized and to the covalently linked desferrioxamines, but also to the carrier material itself. The latter was found to be unspecific and, therefore, the effect of the carrier material remains a field of future research. By means of a reversed CAS assay for various elements (Nd, Gd, La, Er, Al, Ga, V, Au, Fe, As) it was possible to demonstrate improved Ga3+- and Nd3+-binding to desferrioxamine loaded mesoporous silica carriers. The combination of the robust reversed-phase HPLC method and various CAS assays provides new avenues to screen for siderophore producing strains, and to control purification and immobilization of siderophores.}, } @article {pmid30137463, year = {2018}, author = {Hey, J and Chung, Y and Sethuraman, A and Lachance, J and Tishkoff, S and Sousa, VC and Wang, Y}, title = {Phylogeny Estimation by Integration over Isolation with Migration Models.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2805-2818}, pmid = {30137463}, issn = {1537-1719}, support = {R01 DK104339/DK/NIDDK NIH HHS/United States ; R01 GM078204/GM/NIGMS NIH HHS/United States ; S10 OD020095/OD/NIH HHS/United States ; R01 GM113657/GM/NIGMS NIH HHS/United States ; F32 HG006648/HG/NHGRI NIH HHS/United States ; }, abstract = {Phylogeny estimation is difficult for closely related populations and species, especially if they have been exchanging genes. We present a hierarchical Bayesian, Markov-chain Monte Carlo method with a state space that includes all possible phylogenies in a full Isolation-with-Migration model framework. The method is based on a new type of genealogy augmentation called a "hidden genealogy" that enables efficient updating of the phylogeny. This is the first likelihood-based method to fully incorporate directional gene flow and genetic drift for estimation of a species or population phylogeny. Application to human hunter-gatherer populations from Africa revealed a clear phylogenetic history, with strong support for gene exchange with an unsampled ghost population, and relatively ancient divergence between a ghost population and modern human populations, consistent with human/archaic divergence. In contrast, a study of five chimpanzee populations reveals a clear phylogeny with several pairs of populations having exchanged DNA, but does not support a history with an unsampled ghost population.}, } @article {pmid30137422, year = {2018}, author = {Kovar, L and Nageswara-Rao, M and Ortega-Rodriguez, S and Dugas, DV and Straub, S and Cronn, R and Strickler, SR and Hughes, CE and Hanley, KA and Rodriguez, DN and Langhorst, BW and Dimalanta, ET and Bailey, CD}, title = {PacBio-Based Mitochondrial Genome Assembly of Leucaena trichandra (Leguminosae) and an Intrageneric Assessment of Mitochondrial RNA Editing.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2501-2517}, pmid = {30137422}, issn = {1759-6653}, support = {52008103/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Reconstructions of vascular plant mitochondrial genomes (mt-genomes) are notoriously complicated by rampant recombination that has resulted in comparatively few plant mt-genomes being available. The dearth of plant mitochondrial resources has limited our understanding of mt-genome structural diversity, complex patterns of RNA editing, and the origins of novel mt-genome elements. Here, we use an efficient long read (PacBio) iterative assembly pipeline to generate mt-genome assemblies for Leucaena trichandra (Leguminosae: Caesalpinioideae: mimosoid clade), providing the first assessment of non-papilionoid legume mt-genome content and structure to date. The efficiency of the assembly approach facilitated the exploration of alternative structures that are common place among plant mitochondrial genomes. A compact version (729 kbp) of the recovered assemblies was used to investigate sources of mt-genome size variation among legumes and mt-genome sequence similarity to the legume associated root holoparasite Lophophytum. The genome and an associated suite of transcriptome data from select species of Leucaena permitted an in-depth exploration of RNA editing in a diverse clade of closely related species that includes hybrid lineages. RNA editing in the allotetraploid, Leucaena leucocephala, is consistent with co-option of nearly equal maternal and paternal C-to-U edit components, generating novel combinations of RNA edited sites. A preliminary investigation of L. leucocephala C-to-U edit frequencies identified the potential for a hybrid to generate unique pools of alleles from parental variation through edit frequencies shared with one parental lineage, those intermediate between parents, and transgressive patterns.}, } @article {pmid30137400, year = {2018}, author = {Davies, KTJ and Bennett, NC and Faulkes, CG and Rossiter, SJ}, title = {Limited Evidence for Parallel Molecular Adaptations Associated with the Subterranean Niche in Mammals: A Comparative Study of Three Superorders.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2544-2559}, pmid = {30137400}, issn = {1537-1719}, support = {310482//European Research Council/International ; }, abstract = {Among mammals, several lineages have independently adapted to a subterranean niche and possess similar phenotypic traits for burrowing (e.g., cylindrical bodies, short limbs, and absent pinnae). Previous research on mole-rats has revealed molecular adaptations for coping with reduced oxygen, elevated carbon dioxide, and the absence of light. In contrast, almost nothing is known regarding molecular adaptations in other subterranean lineages (e.g., true moles and golden moles). Therefore, the extent to which the recurrent phenotypic adaptations of divergent subterranean taxa have arisen via parallel routes of molecular evolution remains untested. To address these issues, we analyzed ∼8,000 loci in 15 representative subterranean taxa of four independent transitions to an underground niche for signatures of positive selection and convergent amino acid substitutions. Complementary analyses were performed in nonsubterranean "control" taxa to assess the biological significance of results. We found comparable numbers of positively selected genes in each of the four subterranean groups; however, correspondence in terms of gene identity between gene sets was low. Furthermore, we did not detect evidence of more convergent amino acids among subterranean species pairs compared with levels found between nonsubterranean controls. Comparisons with nonsubterranean taxa also revealed loci either under positive selection or with convergent substitutions, with similar functional enrichment (e.g., cell adhesion, immune response, and coagulation). Given the limited indication that positive selection and convergence occurred in the same loci, we conclude that selection may have acted on different loci across subterranean mammal lineages to produce similar phenotypes.}, } @article {pmid30137380, year = {2018}, author = {Liu, J and Robinson-Rechavi, M}, title = {Developmental Constraints on Genome Evolution in Four Bilaterian Model Species.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2266-2277}, pmid = {30137380}, issn = {1759-6653}, abstract = {Developmental constraints on genome evolution have been suggested to follow either an early conservation model or an "hourglass" model. Both models agree that late development strongly diverges between species, but debate on which developmental period is the most conserved. Here, based on a modified "Transcriptome Age Index" approach, that is, weighting trait measures by expression level, we analyzed the constraints acting on three evolutionary traits of protein coding genes (strength of purifying selection on protein sequences, phyletic age, and duplicability) in four species: Nematode worm Caenorhabditis elegans, fly Drosophila melanogaster, zebrafish Danio rerio, and mouse Mus musculus. In general, we found that both models can be supported by different genomic properties. Sequence evolution follows an hourglass model, but the evolution of phyletic age and of duplicability follow an early conservation model. Further analyses indicate that stronger purifying selection on sequences in the middle development are driven by temporal pleiotropy of these genes. In addition, we report evidence that expression in late development is enriched with retrogenes, which usually lack efficient regulatory elements. This implies that expression in late development could facilitate transcription of new genes, and provide opportunities for acquisition of function. Finally, in C. elegans, we suggest that dosage imbalance could be one of the main factors that cause depleted expression of high duplicability genes in early development.}, } @article {pmid30137345, year = {2018}, author = {Luk, AW and Beckmann, S and Manefield, M}, title = {Dependency of DNA extraction efficiency on cell concentration confounds molecular quantification of microorganisms in groundwater.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy146}, pmid = {30137345}, issn = {1574-6941}, abstract = {Quantification of microbes in water systems is essential to industrial practices ranging from drinking water and wastewater treatment to groundwater remediation. While quantification using DNA-based molecular methods is precise, the accuracy is dependent on DNA extraction efficiencies. We show that the DNA yield is strongly impacted by the cell concentration in groundwater samples (r = -0.92, P < 0.0001). This has major implications for industrial applications using quantitative polymerase chain reaction (qPCR) to determine cell concentrations in water, including bioremediation. We propose a simple normalization method using a DNA recovery ratio, calculated with the total cell count and DNA yield. Application of this method to enumeration of bacteria and archaea in groundwater samples targeting phylogenetic markers (16S rRNA) demonstrated an increased goodness of fit after normalization (7.04 vs 0.94 difference in Akaike's information criteria). Furthermore, normalization was applied to qPCR quantification of functional genes and combined with DNA sequencing of archaeal and bacterial 16S rRNA genes to monitor changes in abundance of methanogenic archaea and sulphate-reducing bacteria in groundwater. The integration of qPCR and DNA sequencing with appropriate normalization enables high-throughput quantification of microbial groups using increasingly affordable and accessible techniques. This research has implications for microbial ecology and engineering research as well as industrial practice.}, } @article {pmid30137344, year = {2018}, author = {Kujala, K and Mikkonen, A and Saravesi, K and Ronkanen, AK and Tiirola, M}, title = {Microbial diversity along a gradient in peatlands treating mining-affected waters.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy145}, pmid = {30137344}, issn = {1574-6941}, abstract = {Peatlands are used for the purification of mining-affected waters in Northern Finland. In Northern climate, microorganisms in treatment peatlands (TPs) are affected by long and cold winters, but studies about those microorganisms are scarce. Thus, the bacterial, archaeal and fungal communities along gradients of mine water influence in two TPs were investigated. The TPs receive waters rich in contaminants, including arsenic (As), sulfate (SO42-) and nitrate (NO3-). Microbial diversity was high in both TPs, and microbial community composition differed between the studied TPs. Bacterial communities were dominated by Proteobacteria, Actinobacteria, Chloroflexi and Acidobacteria, archaeal communities were dominated by Methanomicrobia and the Candidate phylum Bathyarchaeota, and fungal communities were dominated by Ascomycota (Leotiomycetes, Dothideomycetes, Sordariomycetes). The functional potential of the bacterial and archaeal communities in TPs was predicted using PICRUSt. Sampling points affected by high concentrations of As showed higher relative abundance of predicted functions related to As resistance. Functions potentially involved in nitrogen and SO42- turnover in TPs were predicted for both TPs. The results obtained in this study indicate that (i) diverse microbial communities exist in Northern TPs, (ii) the functional potential of the peatland microorganisms is beneficial for contaminant removal in TPs and (iii) microorganisms in TPs are likely well-adapted to high contaminant concentrations as well as to the Northern climate.}, } @article {pmid30137329, year = {2018}, author = {Liu, C and Wright, B and Allen-Vercoe, E and Gu, H and Beiko, R}, title = {Phylogenetic Clustering of Genes Reveals Shared Evolutionary Trajectories and Putative Gene Functions.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2255-2265}, pmid = {30137329}, issn = {1759-6653}, support = {U54 HG004969/HG/NHGRI NIH HHS/United States ; }, abstract = {Homologous genes in prokaryotes can be described using phylogenetic profiles which summarize their patterns of presence or absence across a set of genomes. Phylogenetic profiles have been used for nearly twenty years to cluster genes based on measures such as the Euclidean distance between profile vectors. However, most approaches do not take into account the phylogenetic relationships amongst the profiled genomes, and overrepresentation of certain taxonomic groups (i.e., pathogenic species with many sequenced representatives) can skew the interpretation of profiles. We propose a new approach that uses a coevolutionary method defined by Pagel to account for the phylogenetic relationships amongst target organisms, and a hierarchical-clustering approach to define sets of genes with common distributions across the organisms. The clusters we obtain using our method show greater evidence of phylogenetic and functional clustering than a recently published approach based on hidden Markov models. Our clustering method identifies sets of amino-acid biosynthesis genes that constitute cohesive pathways, and motility/chemotaxis genes with common histories of descent and lateral gene transfer.}, } @article {pmid30137328, year = {2018}, author = {Geesink, P and Tyc, O and Küsel, K and Taubert, M and van de Velde, C and Kumar, S and Garbeva, P}, title = {Growth promotion and inhibition induced by interactions of groundwater bacteria.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy164}, pmid = {30137328}, issn = {1574-6941}, abstract = {Microorganisms can produce a plethora of secondary metabolites, some acting as signaling compounds and others as suppressing agents. As yet, the potential of groundwater microbes to produce antimicrobial compounds to increase their competitiveness against other bacteria has not been examined. In this study, we developed an AlamarBlue® based high-throughput screening method that allowed for a fast and highly standardized evaluation of both growth-inhibiting and -promoting metabolites. With this technique, 149 screened bacterial isolates were grown in monocultures and in 1402 co-cultures. Co-cultivation did not increase the frequency of growth inhibition against the two tested model organisms (Staphylococcus aureus 533R4 and Escherichia coli WA321) compared to monocultures. Mainly co-cultivation of Proteobacteria induced growth inhibition of both model organisms. Only slightly increased growth promotion of S. aureus 533R4 was observed. Growth-promoting effects on E. coli WA321 were observed by supernatants from co-cultures between Bacteroidetes and Firmicutes. With the standardized screening for both growth-inhibiting and -promoting effects, this method will enable further studies to elaborate and better understand complex inter-specific interactions and networks in aquatic communities as well as in other environments.}, } @article {pmid30137308, year = {2018}, author = {Shi, PQ and Wang, L and Liu, Y and An, X and Chen, XS and Ahmed, MZ and Qiu, BL and Sang, W}, title = {Infection dynamics of endosymbionts reveal three novel localization patterns of Rickettsia during the development of whitefly Bemisia tabaci.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy165}, pmid = {30137308}, issn = {1574-6941}, abstract = {The whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) is a severe agricultural pest that harbors at least seven endosymbionts. Many important aspects of the symbiosis mechanism between these bacterial endosymbionts and their hosts are poorly understood, such as endosymbiont proliferation dynamics, spatial distribution and titer regulation during host development. In this study, infection by bacterial endosymbionts in the whitefly B. tabaci Middle East-Asia Minor-1 (MEAM1, formerly B biotype) South China population, their infection titers in various stages of whitefly host development and their spatial localization were investigated. Results revealed that the MEAM1 B. tabaci harbors the primary symbiont Portiera and secondary symbionts Rickettsia and Hamiltonella. The titers of these three endosymbionts increased with the development of their B. tabaci host. Significant proliferation of Portiera and Hamiltonella mainly occurred during the second to fourth instar nymphal stages, while Rickettsia proliferated mainly during adult eclosion. Fluorescence in situ hybridization analysis of B. tabaci adults revealed three novel infection patterns of Rickettsia: assemblage in the bacteriocytes that scattered through the entire abdomen of the female host, localization in wax glands and localization in the colleterial gland. These novel infection patterns may help to uncover the function of Rickettsia in its insect hosts.}, } @article {pmid30137302, year = {2018}, author = {Šolic, M and Šantic, D and Šestanovic, S and Bojanic, N and Ordulj, M and Jozic, S and Vrdoljak, A}, title = {The effect of temperature increase on microbial carbon fluxes in the Adriatic Sea: an experimental approach.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy169}, pmid = {30137302}, issn = {1574-6941}, abstract = {An assessment of the temperature increase effect on processes within the microbial food web provides a better insight into the carbon transfer and energy flow processes in marine environments in the global warming perspective. Modified laboratory dilution experiments that allow simultaneous estimates of protozoan grazing and viral lysis on picoplankton groups (bacteria, Prochlorococcus, Synechococcus and pico-eukaryotic algae) under in situ and 3°C above in situ temperatures were performed at seasonal scale. Picoplankton mortality due to grazing was generally higher than that caused by viral lysis, especially in the cold months. The largest part of HNF carbon demand was satisfied by grazing on bacteria throughout the year. Although ciliates satisfied their carbon demand predominantly through grazing on HNF and bacteria, the role of autotrophic picoplankton (APP) as their prey increased significantly in the cold months. Bacteria constituted the most important host for viruses throughout the year. However, during the warm months, APP groups were also significant hosts for viral infection. Under the warming condition the amount of picoplankton biomass transferred to protozoan grazers exceeded the lysed biomass, suggesting that global warming could further increase picoplankton carbon flow toward higher trophic levels in the Adriatic Sea.}, } @article {pmid30137301, year = {2018}, author = {Sirisena, KA and Daughney, CJ and Moreau, M and Sim, DA and Lee, CK and Cary, SC and Ryan, KG and Chambers, GK}, title = {Bacterial bioclusters relate to hydrochemistry in New Zealand groundwater.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy170}, pmid = {30137301}, issn = {1574-6941}, abstract = {Groundwater is a major source of New Zealand's water supply and supports base flows in rivers. Microbial communities in groundwater ecosystems mediate biogeochemical processes, and it is therefore crucial to understand microbial diversity in these ecosystems. We analysed bacterial assemblages from 35 New Zealand groundwater monitoring sites with varying hydrogeochemical conditions across the country. Proteobacteria was the most abundant phylum, and Variovorax represented the most common taxon. Pseudomonas, Burkholderia, Acidovorax, Janthinobacterium, Polaromonas and Caulobacter were the other common taxa. There was no Operational Taxonomic Unit (OTU) that was found in every one of the 35 samples. Here, we introduce a framework that has potential utility for groundwater ecosystem management, where the samples with similar microbial communities are grouped together into 'bioclusters'. Metabolic inferences derived from the taxonomic data were used to predict the oxygen requirements, metabolic potential and bacterial energy sources of each biocluster. Groundwater chemistry explains 59% of the variation in the relative abundance of all OTUs, with NO3-N, pH, DO, NH4-N, Fe, Br and SO4 displaying the strongest relationships to bioclusters. We propose that the biocluster framework, coupled with metabolic inferences derived from the taxonomic data, may have application outside New Zealand for on-going monitoring of the health of groundwater ecosystems.}, } @article {pmid30137299, year = {2018}, author = {Pohlschroder, M and Albers, SV}, title = {Editorial: Editorial for thematic issue on Archaea.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {6}, pages = {719-720}, doi = {10.1093/femsre/fuy032}, pmid = {30137299}, issn = {1574-6976}, mesh = {Archaea/*physiology ; Archaeal Proteins/metabolism ; Environmental Microbiology ; Genome, Archaeal/genetics ; }, } @article {pmid30137298, year = {2018}, author = {Laroche, O and Pochon, X and Tremblay, LA and Ellis, JI and Lear, G and Wood, SA}, title = {Incorporating molecular-based functional and co-occurrence network properties into benthic marine impact assessments.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy167}, pmid = {30137298}, issn = {1574-6941}, abstract = {Taxonomic and functional community structures may respond differently to anthropogenic stressors. Used in combination they can provide an estimate of functional redundancy, a key component of ecosystem resilience. In this study, the utility of incorporating functional community structure and co-occurrence network properties into impact assessments of offshore oil and gas (O&G) operations on benthic bacterial communities was investigated. Sediment samples and physico-chemical data were collected along a transect at increasing distances from one exploratory drilling (ED), and one gas production and drilling (GPD) field. Bacterial community composition was determined by 16S rRNA metabarcoding. A hidden-state prediction method (PAPRICA) was used to characterize bacterial metabolic community functions. At both sites, diversity differed significantly between near-field (impacted) and far-field (non-impacted) stations, with both taxonomic and functional alpha-diversity positively affected in near-field stations at the GPD site. The opposite pattern was observed in the near-field samples of ED with lower and higher values respectively. Overall, impacted stations displayed a distinct network signature, with a lower ratio of positive interactions and signs of higher community cohesion. Community profiles from metabolic inference and co-occurrence network topology provided complementary information to taxonomic indices, which may assist with assessing the effects of O&G activities on benthic communities.}, } @article {pmid30137292, year = {2018}, author = {Alfreider, A and Grimus, V and Luger, M and Ekblad, A and Salcher, MM and Summerer, M}, title = {Autotrophic carbon fixation strategies used by nitrifying prokaryotes in freshwater lakes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, pmid = {30137292}, issn = {1574-6941}, abstract = {Niche specialization of nitrifying prokaryotes is usually studied with tools targeting molecules involved in the oxidation of ammonia and nitrite. The ecological significance of diverse CO2 fixation strategies used by nitrifiers is, however, mostly unexplored. By analyzing autotrophy-related genes in combination with amoA marker genes based on droplet digitial PCR and CARD-FISH counts targeting rRNA, we quantified the distribution of nitrifiers in eight stratified lakes. Ammonia oxidizing (AO) Thaumarchaeota using the 3-hydroxypropionate/4-hydroxybutyrate pathway dominated deep and oligotrophic lakes, whereas Nitrosomonas-related taxa employing the Calvin cycle were important AO bacteria in smaller lakes. The occurrence of nitrite oxidizing Nitrospira, assimilating CO2 with the reductive TCA cycle, was strongly correlated with the distribution of Thaumarchaeota. Recently discovered complete ammonia-oxidizing bacteria (comammox) belonging to Nitrospira accounted only for a very small fraction of ammonia oxidizers (AOs) present at the study sites. Altogether, this study gives a first insight on how physicochemical characteristics in lakes are associated to the distribution of nitrifying prokaryotes with different CO2 fixation strategies. Our investigations also evaluate the suitability of functional genes associated with individual CO2 assimilation pathways to study niche preferences of different guilds of nitrifying microorganisms based on an autotrophic perspective.}, } @article {pmid30137290, year = {2018}, author = {Jamborova, I and Janecko, N and Halova, D and Sedmik, J and Mezerova, K and Papousek, I and Kutilova, I and Dolejska, M and Cizek, A and Literak, I}, title = {Molecular characterization of plasmid-mediated AmpC beta-lactamase- and extended-spectrum beta-lactamase-producing Escherichia coli and Klebsiella pneumoniae among corvids (Corvus brachyrhynchos and Corvus corax) roosting in Canada.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy166}, pmid = {30137290}, issn = {1574-6941}, abstract = {This study evaluated the carriage of AmpC and extended-spectrum beta-lactamase (ESBL) genes and associated plasmids in faecal bacteria of Canadian corvids. Faecal samples from 449 birds in five roosting sites across Canada were analyzed using selective media, screening for AmpC and ESBL genes by PCR, and sequencing. Genomic relatedness was determined by PFGE and MLST. Plasmid mobility was studied by conjugation and transformation experiments, followed by plasmid typing. In total, 96 (21%, n = 449) cefotaxime-resistant Escherichia coli and three (0.7%) Klebsiella pneumoniae isolates were identified. ESBL genes blaCTX-M-1 (n = 3), blaCTX-M-14 (n = 2), blaCTX-M-32 (n = 2) and blaCTX-M-124 (n = 1) were detected in eight E. coli isolates, whereas blaSHV-2 (2) was found in two K. pneumoniae. E. coli isolates contained blaCMY-2 (n = 83) and blaCMY-42 (n = 1). The high genetic diversity of the isolates and presence of clinically important E. coli ST69 (n = 1), ST117 (n = 7) and ST131 (n = 1) was revealed. AmpC genes were predominantly carried by plasmids of incompatibility groups I1 (45 plasmids), A/C (10) and K (7). The plasmid IncI1/ST12 was most common and found in diverse E. coli STs in all sites. Highly diverse E. coli isolates containing AmpC and ESBL genes, including clinically important clones and emerging plasmids, are in circulation throughout Canadian wildlife.}, } @article {pmid30136722, year = {2018}, author = {Layman, NC and Busch, JW}, title = {Bottlenecks and inbreeding depression in autotetraploids.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2025-2037}, doi = {10.1111/evo.13587}, pmid = {30136722}, issn = {1558-5646}, support = {1119000//Division of Environmental Biology/ ; 1457037//Division of Environmental Biology/ ; 1601545//Division of Environmental Biology/ ; }, abstract = {Inbreeding depression is dependent on the ploidy of populations and can inhibit the evolution of selfing. While polyploids should generally harbor less inbreeding depression than diploids at equilibrium, it has been unclear whether this pattern holds in non-equilibrium conditions following bottlenecks. We use stochastic individual-based simulations to determine the effects of population bottlenecks on inbreeding depression in diploids and autotetraploids, in addition to cases where neo-autotetraploids form from the union of unreduced gametes. With a ploidy-independent dominance function based on enzyme kinetics, inbreeding depression is generally lower in autotetraploids for fully and partially recessive mutations. Due to the sampling of more chromosomes during reproduction, bottlenecks generally reduce inbreeding depression to a lesser extent in autotetraploids. All else being equal, population bottlenecks may have ploidy-dependent effects for another reason-in some cases matings between close relatives temporarily increase inbreeding depression in autotetraploids by increasing the frequency of the heterozygous genotype harboring the most harmful mutations. When neo-autotetraploids are formed by few individuals, inbreeding depression is dramatically reduced, given extensive masking of harmful mutations following whole genome duplication. This effect persists as nascent tetraploids reach mutation-selection-drift balance, providing a transient period of permissive conditions favoring the evolution of selfing.}, } @article {pmid30136433, year = {2018}, author = {Mann, DH and Groves, P and Gaglioti, BV and Shapiro, BA}, title = {Climate-driven ecological stability as a globally shared cause of Late Quaternary megafaunal extinctions: the Plaids and Stripes Hypothesis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12456}, pmid = {30136433}, issn = {1469-185X}, abstract = {Controversy persists about why so many large-bodied mammal species went extinct around the end of the last ice age. Resolving this is important for understanding extinction processes in general, for assessing the ecological roles of humans, and for conserving remaining megafaunal species, many of which are endangered today. Here we explore an integrative hypothesis that asserts that an underlying cause of Late Quaternary megafaunal extinctions was a fundamental shift in the spatio-temporal fabric of ecosystems worldwide. This shift was triggered by the loss of the millennial-scale climate fluctuations that were characteristic of the ice age but ceased approximately 11700 years ago on most continents. Under ice-age conditions, which prevailed for much of the preceding 2.6 Ma, these radical and rapid climate changes prevented many ecosystems from fully equilibrating with their contemporary climates. Instead of today's 'striped' world in which species' ranges have equilibrated with gradients of temperature, moisture, and seasonality, the ice-age world was a disequilibrial 'plaid' in which species' ranges shifted rapidly and repeatedly over time and space, rarely catching up with contemporary climate. In the transient ecosystems that resulted, certain physiological, anatomical, and ecological attributes shared by megafaunal species pre-adapted them for success. These traits included greater metabolic and locomotory efficiency, increased resistance to starvation, longer life spans, greater sensory ranges, and the ability to be nomadic or migratory. When the plaid world of the ice age ended, many of the advantages of being large were either lost or became disadvantages. For instance in a striped world, the low population densities and slow reproductive rates associated with large body size reduced the resiliency of megafaunal species to population bottlenecks. As the ice age ended, the downsides of being large in striped environments lowered the extinction thresholds of megafauna worldwide, which then increased the vulnerability of individual species to a variety of proximate threats they had previously tolerated, such as human predation, competition with other species, and habitat loss. For many megafaunal species, the plaid-to-stripes transition may have been near the base of a hierarchy of extinction causes whose relative importances varied geographically, temporally, and taxonomically.}, } @article {pmid30136425, year = {2018}, author = {Narihiro, T and Nobu, MK and Bocher, BTW and Mei, R and Liu, WT}, title = {Co-occurrence network analysis reveals thermodynamics-driven microbial interactions in methanogenic bioreactors.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {673-685}, doi = {10.1111/1758-2229.12689}, pmid = {30136425}, issn = {1758-2229}, abstract = {Methanogenic bioreactors have been applied to treat purified terephthalic acid (PTA) wastewater containing complex aromatic compounds, such as terephthalic acid, para-toluic acid and benzoic acid. This study characterized the interaction of microbial populations in 42 samples obtained from 10 PTA-degrading methanogenic bioreactors. Approximately, 54 dominant populations (11 methanogens, 8 syntrophs and 35 functionally unknown clades) that represented 73.9% of total 16S rRNA gene iTag sequence reads were identified. Co-occurrence analysis based on the abundance of dominant OTUs showed two non-overlapping networks centred around aromatic compound- (group AR: Syntrophorhabdaceae, Syntrophus and Pelotomaculum) and fatty acid- (group FA: Smithella and Syntrophobacter) degrading syntrophs. Group AR syntrophs have no direct correlation with hydrogenotrophic methanogens, while those from group FA do. As degradation of aromatic compounds has a wider thermodynamic window than fatty acids, Group AR syntrophs may be less influenced by fluctuations in hydrogenotrophic methanogen abundance or may non-specifically interact with diverse methanogens. In both groups, network analysis reveals full-scale- and lab-scale-specific uncultivated taxa that may mediate interactions between syntrophs and methanogens, suggesting that those uncultivated taxa may support the degradation of aromatic compounds through uncharted ecophysiological traits. These observations suggest that organisms from multiple niches orchestrate their metabolic capacity in multiple interaction networks to effectively degrade PTA wastewater.}, } @article {pmid30136386, year = {2019}, author = {Urakawa, H and Rajan, S and Feeney, ME and Sobecky, PA and Mortazavi, B}, title = {Ecological response of nitrification to oil spills and its impact on the nitrogen cycle.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {18-33}, doi = {10.1111/1462-2920.14391}, pmid = {30136386}, issn = {1462-2920}, support = {1664052//Division of Environmental Biology/ ; //Florida Gulf Coast University/ ; //Gulf of Mexico Research Initiative/ ; }, abstract = {Marine oil spills are catastrophic events that cause massive damage to ecosystems at all trophic levels. While most of the research has focused on carbon-degrading microorganisms, the potential impacts of hydrocarbons on microbes responsible for nitrification have received far less attention. Nitrifiers are sensitive to hydrocarbon toxicity: ammonia-oxidizing bacteria and archaea being 100 and 1000 times more sensitive than typical heterotrophs respectively. Field studies have demonstrated the response of nitrifiers to hydrocarbons is highly variable and the loss of nitrification activity in coastal ecosystems can be restored within 1-2 years, which is much shorter than the typical recovery time of whole ecosystems (e.g., up to 20 years). Since the denitrification process is mainly driven by heterotrophs, which are more resistant to hydrocarbon toxicity than nitrifiers, the inhibition of nitrification may slow down the nitrogen turnover and increase ammonia availability, which supports the growth of oil-degrading heterotrophs and possibly various phototrophs. A better understanding of the ecological response of nitrification is paramount in predicting impacts of oil spills on the nitrogen cycle under oil spill conditions, and in improving current bioremediation practices.}, } @article {pmid30136362, year = {2018}, author = {Jourdan, J and Plath, M and Tonkin, JD and Ceylan, M and Dumeier, AC and Gellert, G and Graf, W and Hawkins, CP and Kiel, E and Lorenz, AW and Matthaei, CD and Verdonschot, PFM and Verdonschot, RCM and Haase, P}, title = {Reintroduction of freshwater macroinvertebrates: challenges and opportunities.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12458}, pmid = {30136362}, issn = {1469-185X}, abstract = {Species reintroductions - the translocation of individuals to areas in which a species has been extirpated with the aim of re-establishing a self-sustaining population - have become a widespread practice in conservation biology. Reintroduction projects have tended to focus on terrestrial vertebrates and, to a lesser extent, fishes. Much less effort has been devoted to the reintroduction of invertebrates into restored freshwater habitats. Yet, reintroductions may improve restoration outcomes in regions where impoverished regional species pools limit the self-recolonisation of restored freshwaters. We review the available literature on macroinvertebrate reintroductions, focusing on identifying the intrinsic and extrinsic factors that determine their success or failure. Our study reveals that freshwater macroinvertebrate reintroductions remain rare, are often published in the grey literature and, of the attempts made, approximately one-third fail. We identify life-cycle complexity and remaining stressors as the two factors most likely to affect reintroduction success, illustrating the unique challenges of freshwater macroinvertebrate reintroductions. Consideration of these factors by managers during the planning process and proper documentation - even if a project fails - may increase the likelihood of successful outcomes in future reintroduction attempts of freshwater macroinvertebrates.}, } @article {pmid30136361, year = {2018}, author = {Ran, C and Qin, C and Xie, M and Zhang, J and Li, J and Xie, Y and Wang, Y and Li, S and Liu, L and Fu, X and Lin, Q and Li, N and Liles, MR and Zhou, Z}, title = {Aeromonas veronii and aerolysin are important for the pathogenesis of motile aeromonad septicemia in cyprinid fish.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3442-3456}, doi = {10.1111/1462-2920.14390}, pmid = {30136361}, issn = {1462-2920}, support = {973//Fundamental Research and Development/ ; 2015CB150605//Ministry of Science and Technology/ ; 31572633//National Natural Science Foundation of China/ ; 31602169//National Natural Science Foundation of China/ ; 1610382017008//Chinese Academy of Agricultural Sciences/ ; }, abstract = {Aeromonas species are ubiquitous inhabitants of freshwater environments, and are responsible for fish motile aeromonad septicemia (MAS). A. hydrophila is implicated as the primary etiologic agent of MAS. Here, we analysed MAS epidemiological data for cyprinid fish in southern China, and found that A. veronii infections dominated. Consistent with this observation, A. veronii isolates were generally more virulent than A. hydrophila isolates when infecting germ-free zebrafish larvae via continuous immersion challenge. Through in vivo screening of the transposon library of the A. veronii strain Hm091, aerolysin was identified as the key virulence factor. Further results indicated that A. veronii Hm091 aerolysin disrupts the intestinal barrier of zebrafish, enabling systematic invasion by not only A. veronii Hm091 in a mono-infection, but also A. hydrophila NJ-1 in a mixed infection. Moreover, the differences in aerolysin expression and activity were the major contributor to the observed differences between the A. veronii and A. hydrophila strains regarding invasion efficacy via intestine. Together, our results provide new insights into the aetiology and pathogenesis of Aeromonas infections, and highlight the importance of A. veronii-targeted treatments in future efforts against MAS.}, } @article {pmid30136358, year = {2018}, author = {Koehler, S and Gaedeke, R and Thompson, C and Bongrand, C and Visick, KL and Ruby, E and McFall-Ngai, M}, title = {The model squid-vibrio symbiosis provides a window into the impact of strain- and species-level differences during the initial stages of symbiont engagement.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14392}, pmid = {30136358}, issn = {1462-2920}, support = {R01 AI050661/AI/NIAID NIH HHS/United States ; R37 AI150661//National Institute of Health/ ; GM114288//National Institute of Health/ ; R01 OD011024/OD/NIH HHS/United States ; R37 AI050661/AI/NIAID NIH HHS/United States ; R01 OD11024//National Institute of Health/ ; }, abstract = {Among horizontally acquired symbioses, the mechanisms underlying microbial strain- and species-level specificity remain poorly understood. Here, confocal-microscopy analyses and genetic manipulation of the squid-vibrio association revealed quantitative differences in a symbiont's capacity to interact with the host during initial engagement. Specifically, dominant strains of Vibrio fischeri, 'D-type', previously named for their dominant, single-strain colonization of the squid's bioluminescent organ, were compared with 'S-type', or 'sharing', strains, which can co-colonize the organ. These D-type strains typically: (i) formed aggregations of 100s-1000s of cells on the light-organ surface, up to 3 orders of magnitude larger than those of S-type strains; (ii) showed dominance in co-aggregation experiments, independent of inoculum size or strain proportion; (iii) perturbed larger areas of the organ's ciliated surface; and, (iv) appeared at the pore of the organ approximately 4×s more quickly than S-type strains. At least in part, genes responsible for biofilm synthesis control the hyperaggregation phenotype of a D-type strain. Other marine vibrios produced relatively small aggregations, while an array of marine Gram-positive and -negative species outside of the Vibrionaceae did not attach to the organ's surface. These studies provide insight into the impact of strain variation on early events leading to establishment of an environmentally acquired symbiosis.}, } @article {pmid30136352, year = {2018}, author = {Lechtenfeld, M and Heine, J and Sameith, J and Kremp, F and Müller, V}, title = {Glycine betaine metabolism in the acetogenic bacterium Acetobacterium woodii.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4512-4525}, doi = {10.1111/1462-2920.14389}, pmid = {30136352}, issn = {1462-2920}, support = {741791//European Research Council/International ; }, abstract = {The quarternary, trimethylated amine glycine betaine (GB) is widespread in nature but its fate under anoxic conditions remains elusive. It can be used by some acetogenic bacteria as carbon and energy source but the pathway of GB metabolism has not been elucidated. We have identified a gene cluster involved in GB metabolism and studied acetogenesis from GB in the model acetogen Acetobacterium woodii. GB is taken up by a secondary active, Na+ coupled transporter of the betaine-choline-carnitine (BCC) family. GB is demethylated to dimethylglycine, the end product of the reaction, by a methyltransferase system. Further conversion of the methyl group requires CO2 as well as Na+ indicating that GB metabolism involves the Wood-Ljungdahl pathway. These studies culminate in a model for the path of carbon and electrons during acetogenensis from GB and a model for the bioenergetics of acetogenesis from GB.}, } @article {pmid30135588, year = {2018}, author = {Ahmadi, M and Alves, BXR and Baker, CJ and Bertsche, W and Capra, A and Carruth, C and Cesar, CL and Charlton, M and Cohen, S and Collister, R and Eriksson, S and Evans, A and Evetts, N and Fajans, J and Friesen, T and Fujiwara, MC and Gill, DR and Hangst, JS and Hardy, WN and Hayden, ME and Hunter, ED and Isaac, CA and Johnson, MA and Jones, JM and Jones, SA and Jonsell, S and Khramov, A and Knapp, P and Kurchaninov, L and Madsen, N and Maxwell, D and McKenna, JTK and Menary, S and Michan, JM and Momose, T and Munich, JJ and Olchanski, K and Olin, A and Pusa, P and Rasmussen, CØ and Robicheaux, F and Sacramento, RL and Sameed, M and Sarid, E and Silveira, DM and Starko, DM and Stutter, G and So, C and Tharp, TD and Thompson, RI and van der Werf, DP and Wurtele, JS}, title = {Observation of the 1S-2P Lyman-α transition in antihydrogen.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {211-215}, doi = {10.1038/s41586-018-0435-1}, pmid = {30135588}, issn = {1476-4687}, abstract = {In 1906, Theodore Lyman discovered his eponymous series of transitions in the extreme-ultraviolet region of the atomic hydrogen spectrum1,2. The patterns in the hydrogen spectrum helped to establish the emerging theory of quantum mechanics, which we now know governs the world at the atomic scale. Since then, studies involving the Lyman-α line-the 1S-2P transition at a wavelength of 121.6 nanometres-have played an important part in physics and astronomy, as one of the most fundamental atomic transitions in the Universe. For example, this transition has long been used by astronomers studying the intergalactic medium and testing cosmological models via the so-called 'Lyman-α forest'3 of absorption lines at different redshifts. Here we report the observation of the Lyman-α transition in the antihydrogen atom, the antimatter counterpart of hydrogen. Using narrow-line-width, nanosecond-pulsed laser radiation, the 1S-2P transition was excited in magnetically trapped antihydrogen. The transition frequency at a field of 1.033 tesla was determined to be 2,466,051.7 ± 0.12 gigahertz (1σ uncertainty) and agrees with the prediction for hydrogen to a precision of 5 × 10-8. Comparisons of the properties of antihydrogen with those of its well-studied matter equivalent allow precision tests of fundamental symmetries between matter and antimatter. Alongside the ground-state hyperfine4,5 and 1S-2S transitions6,7 recently observed in antihydrogen, the Lyman-α transition will permit laser cooling of antihydrogen8,9, thus providing a cold and dense sample of anti-atoms for precision spectroscopy and gravity measurements10. In addition to the observation of this fundamental transition, this work represents both a decisive technological step towards laser cooling of antihydrogen, and the extension of antimatter spectroscopy to quantum states possessing orbital angular momentum.}, } @article {pmid30135587, year = {2018}, author = {Peng, J and Cao, D and He, Z and Guo, J and Hapala, P and Ma, R and Cheng, B and Chen, J and Xie, WJ and Li, XZ and Jelínek, P and Xu, LM and Gao, YQ and Wang, EG and Jiang, Y}, title = {Publisher Correction: The effect of hydration number on the interfacial transport of sodium ions.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {E18}, doi = {10.1038/s41586-018-0473-8}, pmid = {30135587}, issn = {1476-4687}, abstract = {In this Letter, the links to Supplementary Videos 5, 7, 9 and 10 were incorrect, and there were some formatting errors in the Supplementary Video legends. These errors have been corrected online.}, } @article {pmid30135586, year = {2018}, author = {Hetherington, AJ and Dolan, L}, title = {Stepwise and independent origins of roots among land plants.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {235-238}, pmid = {30135586}, issn = {1476-4687}, abstract = {Roots are one of the three fundamental organ systems of vascular plants1, and have roles in anchorage, symbiosis, and nutrient and water uptake2-4. However, the fragmentary nature of the fossil record obscures the origins of roots and makes it difficult to identify when the sole defining characteristic of extant roots-the presence of self-renewing structures called root meristems that are covered by a root cap at their apex1-9-evolved. Here we report the discovery of what are-to our knowledge-the oldest meristems of rooting axes, found in the earliest-preserved terrestrial ecosystem10 (the 407-million-year-old Rhynie chert). These meristems, which belonged to the lycopsid Asteroxylon mackiei11-14, lacked root caps and instead developed a continuous epidermis over the surface of the meristem. The rooting axes and meristems of A. mackiei are unique among vascular plants. These data support the hypothesis that roots, as defined in extant vascular plants by the presence of a root cap7, were a late innovation in the vascular lineage. Roots therefore acquired traits in a stepwise fashion. The relatively late origin in lycophytes of roots with caps is consistent with the hypothesis that roots evolved multiple times2 rather than having a single origin1, and the extensive similarities between lycophyte and euphyllophyte roots15-18 therefore represent examples of convergent evolution. The key phylogenetic position of A. mackiei-with its transitional rooting organ-between early diverging land plants that lacked roots and derived plants that developed roots demonstrates how roots were 'assembled' during the course of plant evolution.}, } @article {pmid30135585, year = {2018}, author = {Sliter, DA and Martinez, J and Hao, L and Chen, X and Sun, N and Fischer, TD and Burman, JL and Li, Y and Zhang, Z and Narendra, DP and Cai, H and Borsche, M and Klein, C and Youle, RJ}, title = {Parkin and PINK1 mitigate STING-induced inflammation.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {258-262}, doi = {10.1038/s41586-018-0448-9}, pmid = {30135585}, issn = {1476-4687}, support = {1ZIAES10328601/ES/NIEHS NIH HHS/United States ; DFG FOR2488/AA/NIAAA NIH HHS/United States ; }, abstract = {Although serum from patients with Parkinson's disease contains elevated levels of numerous pro-inflammatory cytokines including IL-6, TNF, IL-1β, and IFNγ, whether inflammation contributes to or is a consequence of neuronal loss remains unknown1. Mutations in parkin, an E3 ubiquitin ligase, and PINK1, a ubiquitin kinase, cause early onset Parkinson's disease2,3. Both PINK1 and parkin function within the same biochemical pathway and remove damaged mitochondria from cells in culture and in animal models via mitophagy, a selective form of autophagy4. The in vivo role of mitophagy, however, is unclear, partly because mice that lack either PINK1 or parkin have no substantial Parkinson's-disease-relevant phenotypes5-7. Mitochondrial stress can lead to the release of damage-associated molecular patterns (DAMPs) that can activate innate immunity8-12, suggesting that mitophagy may mitigate inflammation. Here we report a strong inflammatory phenotype in both Prkn-/- and Pink1-/- mice following exhaustive exercise and in Prkn-/-;mutator mice, which accumulate mutations in mitochondrial DNA (mtDNA)13,14. Inflammation resulting from either exhaustive exercise or mtDNA mutation is completely rescued by concurrent loss of STING, a central regulator of the type I interferon response to cytosolic DNA15,16. The loss of dopaminergic neurons from the substantia nigra pars compacta and the motor defect observed in aged Prkn-/-;mutator mice are also rescued by loss of STING, suggesting that inflammation facilitates this phenotype. Humans with mono- and biallelic PRKN mutations also display elevated cytokines. These results support a role for PINK1- and parkin-mediated mitophagy in restraining innate immunity.}, } @article {pmid30135584, year = {2018}, author = {Zhang, W and Wan, H and Feng, G and Qu, J and Wang, J and Jing, Y and Ren, R and Liu, Z and Zhang, L and Chen, Z and Wang, S and Zhao, Y and Wang, Z and Yuan, Y and Zhou, Q and Li, W and Liu, GH and Hu, B}, title = {SIRT6 deficiency results in developmental retardation in cynomolgus monkeys.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {661-665}, doi = {10.1038/s41586-018-0437-z}, pmid = {30135584}, issn = {1476-4687}, abstract = {SIRT6 acts as a longevity protein in rodents1,2. However, its biological function in primates remains largely unknown. Here we generate a SIRT6-null cynomolgus monkey (Macaca fascicularis) model using a CRISPR-Cas9-based approach. SIRT6-deficient monkeys die hours after birth and exhibit severe prenatal developmental retardation. SIRT6 loss delays neuronal differentiation by transcriptionally activating the long non-coding RNA H19 (a developmental repressor), and we were able to recapitulate this process in a human neural progenitor cell differentiation system. SIRT6 deficiency results in histone hyperacetylation at the imprinting control region of H19, CTCF recruitment and upregulation of H19. Our results suggest that SIRT6 is involved in regulating development in non-human primates, and may provide mechanistic insight into human perinatal lethality syndrome.}, } @article {pmid30135583, year = {2018}, author = {Roy Chowdhury, R and Vallania, F and Yang, Q and Lopez Angel, CJ and Darboe, F and Penn-Nicholson, A and Rozot, V and Nemes, E and Malherbe, ST and Ronacher, K and Walzl, G and Hanekom, W and Davis, MM and Winter, J and Chen, X and Scriba, TJ and Khatri, P and Chien, YH}, title = {A multi-cohort study of the immune factors associated with M. tuberculosis infection outcomes.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {644-648}, doi = {10.1038/s41586-018-0439-x}, pmid = {30135583}, issn = {1476-4687}, support = {R21 AI127128/AI/NIAID NIH HHS/United States ; T32 AI007290/AI/NIAID NIH HHS/United States ; AI057229/NH/NIH HHS/United States ; AI109662//National Institutes of Health/International ; AI125197/NH/NIH HHS/United States ; K12 5K12HL120001/NH/NIH HHS/United States ; 5T32AI07290-31/NH/NIH HHS/United States ; }, abstract = {Most infections with Mycobacterium tuberculosis (Mtb) manifest as a clinically asymptomatic, contained state, known as latent tuberculosis infection, that affects approximately one-quarter of the global population1. Although fewer than one in ten individuals eventually progress to active disease2, tuberculosis is a leading cause of death from infectious disease worldwide3. Despite intense efforts, immune factors that influence the infection outcomes remain poorly defined. Here we used integrated analyses of multiple cohorts to identify stage-specific host responses to Mtb infection. First, using high-dimensional mass cytometry analyses and functional assays of a cohort of South African adolescents, we show that latent tuberculosis is associated with enhanced cytotoxic responses, which are mostly mediated by CD16 (also known as FcγRIIIa) and natural killer cells, and continuous inflammation coupled with immune deviations in both T and B cell compartments. Next, using cell-type deconvolution of transcriptomic data from several cohorts of different ages, genetic backgrounds, geographical locations and infection stages, we show that although deviations in peripheral B and T cell compartments generally start at latency, they are heterogeneous across cohorts. However, an increase in the abundance of circulating natural killer cells in tuberculosis latency, with a corresponding decrease during active disease and a return to baseline levels upon clinical cure are features that are common to all cohorts. Furthermore, by analysing three longitudinal cohorts, we find that changes in peripheral levels of natural killer cells can inform disease progression and treatment responses, and inversely correlate with the inflammatory state of the lungs of patients with active tuberculosis. Together, our findings offer crucial insights into the underlying pathophysiology of tuberculosis latency, and identify factors that may influence infection outcomes.}, } @article {pmid30135582, year = {2018}, author = {Meng, Z and Qiu, Y and Lin, KC and Kumar, A and Placone, JK and Fang, C and Wang, KC and Lu, S and Pan, M and Hong, AW and Moroishi, T and Luo, M and Plouffe, SW and Diao, Y and Ye, Z and Park, HW and Wang, X and Yu, FX and Chien, S and Wang, CY and Ren, B and Engler, AJ and Guan, KL}, title = {RAP2 mediates mechanoresponses of the Hippo pathway.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {655-660}, pmid = {30135582}, issn = {1476-4687}, support = {R01 CA206880/CA/NCI NIH HHS/United States ; R35 CA196878/CA/NCI NIH HHS/United States ; DP2 OD006460/OD/NIH HHS/United States ; R01 GM051586/GM/NIGMS NIH HHS/United States ; F32 HL126406/HL/NHLBI NIH HHS/United States ; T32 GM007752/GM/NIGMS NIH HHS/United States ; R21 CA217735/CA/NCI NIH HHS/United States ; R01 CA217642/CA/NCI NIH HHS/United States ; T32 AR060712/AR/NIAMS NIH HHS/United States ; }, abstract = {Mammalian cells are surrounded by neighbouring cells and extracellular matrix (ECM), which provide cells with structural support and mechanical cues that influence diverse biological processes1. The Hippo pathway effectors YAP (also known as YAP1) and TAZ (also known as WWTR1) are regulated by mechanical cues and mediate cellular responses to ECM stiffness2,3. Here we identified the Ras-related GTPase RAP2 as a key intracellular signal transducer that relays ECM rigidity signals to control mechanosensitive cellular activities through YAP and TAZ. RAP2 is activated by low ECM stiffness, and deletion of RAP2 blocks the regulation of YAP and TAZ by stiffness signals and promotes aberrant cell growth. Mechanistically, matrix stiffness acts through phospholipase Cγ1 (PLCγ1) to influence levels of phosphatidylinositol 4,5-bisphosphate and phosphatidic acid, which activates RAP2 through PDZGEF1 and PDZGEF2 (also known as RAPGEF2 and RAPGEF6). At low stiffness, active RAP2 binds to and stimulates MAP4K4, MAP4K6, MAP4K7 and ARHGAP29, resulting in activation of LATS1 and LATS2 and inhibition of YAP and TAZ. RAP2, YAP and TAZ have pivotal roles in mechanoregulated transcription, as deletion of YAP and TAZ abolishes the ECM stiffness-responsive transcriptome. Our findings show that RAP2 is a molecular switch in mechanotransduction, thereby defining a mechanosignalling pathway from ECM stiffness to the nucleus.}, } @article {pmid30135581, year = {2018}, author = {Ordovas-Montanes, J and Dwyer, DF and Nyquist, SK and Buchheit, KM and Vukovic, M and Deb, C and Wadsworth, MH and Hughes, TK and Kazer, SW and Yoshimoto, E and Cahill, KN and Bhattacharyya, N and Katz, HR and Berger, B and Laidlaw, TM and Boyce, JA and Barrett, NA and Shalek, AK}, title = {Allergic inflammatory memory in human respiratory epithelial progenitor cells.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {649-654}, pmid = {30135581}, issn = {1476-4687}, support = {R01 HL128241/HL/NHLBI NIH HHS/United States ; R01 HL095791/HL/NHLBI NIH HHS/United States ; R01 HL134539/HL/NHLBI NIH HHS/United States ; R01 AI138546/AI/NIAID NIH HHS/United States ; T32 AI007306/AI/NIAID NIH HHS/United States ; U19 AI095219/AI/NIAID NIH HHS/United States ; U19 AI070535/AI/NIAID NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; DP2 GM119419/GM/NIGMS NIH HHS/United States ; R01 AI078908/AI/NIAID NIH HHS/United States ; P01 AI039671/AI/NIAID NIH HHS/United States ; R33 CA202820/CA/NCI NIH HHS/United States ; R01 GM081871/GM/NIGMS NIH HHS/United States ; R01 HL120952/HL/NHLBI NIH HHS/United States ; R01 HL136209/HL/NHLBI NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; U24 AI118672/AI/NIAID NIH HHS/United States ; R37 AI052353/AI/NIAID NIH HHS/United States ; R56 HL126554/HL/NHLBI NIH HHS/United States ; R01 AI136041/AI/NIAID NIH HHS/United States ; P30 AI060354/AI/NIAID NIH HHS/United States ; K23 AI118804/AI/NIAID NIH HHS/United States ; RM1 HG006193/HG/NHGRI NIH HHS/United States ; U54 CA217377/CA/NCI NIH HHS/United States ; 1DP2OD020839/NH/NIH HHS/United States ; R01 DA046277/DA/NIDA NIH HHS/United States ; }, abstract = {Barrier tissue dysfunction is a fundamental feature of chronic human inflammatory diseases1. Specialized subsets of epithelial cells-including secretory and ciliated cells-differentiate from basal stem cells to collectively protect the upper airway2-4. Allergic inflammation can develop from persistent activation5 of type 2 immunity6 in the upper airway, resulting in chronic rhinosinusitis, which ranges in severity from rhinitis to severe nasal polyps7. Basal cell hyperplasia is a hallmark of severe disease7-9, but it is not known how these progenitor cells2,10,11 contribute to clinical presentation and barrier tissue dysfunction in humans. Here we profile primary human surgical chronic rhinosinusitis samples (18,036 cells, n = 12) that span the disease spectrum using Seq-Well for massively parallel single-cell RNA sequencing12, report transcriptomes for human respiratory epithelial, immune and stromal cell types and subsets from a type 2 inflammatory disease, and map key mediators. By comparison with nasal scrapings (18,704 cells, n = 9), we define signatures of core, healthy, inflamed and polyp secretory cells. We reveal marked differences between the epithelial compartments of the non-polyp and polyp cellular ecosystems, identifying and validating a global reduction in cellular diversity of polyps characterized by basal cell hyperplasia, concomitant decreases in glandular cells, and phenotypic shifts in secretory cell antimicrobial expression. We detect an aberrant basal progenitor differentiation trajectory in polyps, and propose cell-intrinsic13, epigenetic14,15 and extrinsic factors11,16,17 that lock polyp basal cells into this uncommitted state. Finally, we functionally demonstrate that ex vivo cultured basal cells retain intrinsic memory of IL-4/IL-13 exposure, and test the potential for clinical blockade of the IL-4 receptor α-subunit to modify basal and secretory cell states in vivo. Overall, we find that reduced epithelial diversity stemming from functional shifts in basal cells is a key characteristic of type 2 immune-mediated barrier tissue dysfunction. Our results demonstrate that epithelial stem cells may contribute to the persistence of human disease by serving as repositories for allergic memories.}, } @article {pmid30135580, year = {2018}, author = {Vos, SM and Farnung, L and Urlaub, H and Cramer, P}, title = {Structure of paused transcription complex Pol II-DSIF-NELF.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {601-606}, pmid = {30135580}, issn = {1476-4687}, abstract = {Metazoan gene regulation often involves the pausing of RNA polymerase II (Pol II) in the promoter-proximal region. Paused Pol II is stabilized by the protein complexes DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF). Here we report the cryo-electron microscopy structure of a paused transcription elongation complex containing Sus scrofa Pol II and Homo sapiens DSIF and NELF at 3.2 Å resolution. The structure reveals a tilted DNA-RNA hybrid that impairs binding of the nucleoside triphosphate substrate. NELF binds the polymerase funnel, bridges two mobile polymerase modules, and contacts the trigger loop, thereby restraining Pol II mobility that is required for pause release. NELF prevents binding of the anti-pausing transcription elongation factor IIS (TFIIS). Additionally, NELF possesses two flexible 'tentacles' that can contact DSIF and exiting RNA. These results define the paused state of Pol II and provide the molecular basis for understanding the function of NELF during promoter-proximal gene regulation.}, } @article {pmid30135579, year = {2018}, author = {Slon, V and Mafessoni, F and Vernot, B and de Filippo, C and Grote, S and Viola, B and Hajdinjak, M and Peyrégne, S and Nagel, S and Brown, S and Douka, K and Higham, T and Kozlikin, MB and Shunkov, MV and Derevianko, AP and Kelso, J and Meyer, M and Prüfer, K and Pääbo, S}, title = {The genome of the offspring of a Neanderthal mother and a Denisovan father.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {113-116}, pmid = {30135579}, issn = {1476-4687}, abstract = {Neanderthals and Denisovans are extinct groups of hominins that separated from each other more than 390,000 years ago1,2. Here we present the genome of 'Denisova 11', a bone fragment from Denisova Cave (Russia)3 and show that it comes from an individual who had a Neanderthal mother and a Denisovan father. The father, whose genome bears traces of Neanderthal ancestry, came from a population related to a later Denisovan found in the cave4-6. The mother came from a population more closely related to Neanderthals who lived later in Europe2,7 than to an earlier Neanderthal found in Denisova Cave8, suggesting that migrations of Neanderthals between eastern and western Eurasia occurred sometime after 120,000 years ago. The finding of a first-generation Neanderthal-Denisovan offspring among the small number of archaic specimens sequenced to date suggests that mixing between Late Pleistocene hominin groups was common when they met.}, } @article {pmid30135578, year = {2018}, author = {Vos, SM and Farnung, L and Boehning, M and Wigge, C and Linden, A and Urlaub, H and Cramer, P}, title = {Structure of activated transcription complex Pol II-DSIF-PAF-SPT6.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {607-612}, doi = {10.1038/s41586-018-0440-4}, pmid = {30135578}, issn = {1476-4687}, abstract = {Gene regulation involves activation of RNA polymerase II (Pol II) that is paused and bound by the protein complexes DRB sensitivity-inducing factor (DSIF) and negative elongation factor (NELF). Here we show that formation of an activated Pol II elongation complex in vitro requires the kinase function of the positive transcription elongation factor b (P-TEFb) and the elongation factors PAF1 complex (PAF) and SPT6. The cryo-EM structure of an activated elongation complex of Sus scrofa Pol II and Homo sapiens DSIF, PAF and SPT6 was determined at 3.1 Å resolution and compared to the structure of the paused elongation complex formed by Pol II, DSIF and NELF. PAF displaces NELF from the Pol II funnel for pause release. P-TEFb phosphorylates the Pol II linker to the C-terminal domain. SPT6 binds to the phosphorylated C-terminal-domain linker and opens the RNA clamp formed by DSIF. These results provide the molecular basis for Pol II pause release and elongation activation.}, } @article {pmid30135577, year = {2018}, author = {Yang, S and Wu, Y and Xu, TH and de Waal, PW and He, Y and Pu, M and Chen, Y and DeBruine, ZJ and Zhang, B and Zaidi, SA and Popov, P and Guo, Y and Han, GW and Lu, Y and Suino-Powell, K and Dong, S and Harikumar, KG and Miller, LJ and Katritch, V and Xu, HE and Shui, W and Stevens, RC and Melcher, K and Zhao, S and Xu, F}, title = {Crystal structure of the Frizzled 4 receptor in a ligand-free state.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {666-670}, doi = {10.1038/s41586-018-0447-x}, pmid = {30135577}, issn = {1476-4687}, abstract = {Frizzled receptors (FZDs) are class-F G-protein-coupled receptors (GPCRs) that function in Wnt signalling and are essential for developing and adult organisms1,2. As central mediators in this complex signalling pathway, FZDs serve as gatekeeping proteins both for drug intervention and for the development of probes in basic and in therapeutic research. Here we present an atomic-resolution structure of the human Frizzled 4 receptor (FZD4) transmembrane domain in the absence of a bound ligand. The structure reveals an unusual transmembrane architecture in which helix VI is short and tightly packed, and is distinct from all other GPCR structures reported so far. Within this unique transmembrane fold is an extremely narrow and highly hydrophilic pocket that is not amenable to the binding of traditional GPCR ligands. We show that such a pocket is conserved across all FZDs, which may explain the long-standing difficulties in the development of ligands for these receptors. Molecular dynamics simulations on the microsecond timescale and mutational analysis uncovered two coupled, dynamic kinks located at helix VII that are involved in FZD4 activation. The stability of the structure in its ligand-free form, an unfavourable pocket for ligand binding and the two unusual kinks on helix VII suggest that FZDs may have evolved a novel ligand-recognition and activation mechanism that is distinct from that of other GPCRs.}, } @article {pmid30135576, year = {2018}, author = {Ulrich, Y and Saragosti, J and Tokita, CK and Tarnita, CE and Kronauer, DJC}, title = {Fitness benefits and emergent division of labour at the onset of group living.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {635-638}, pmid = {30135576}, issn = {1476-4687}, support = {DP2 GM105454/GM/NIGMS NIH HHS/United States ; }, abstract = {The initial fitness benefits of group living are considered to be the greatest hurdle to the evolution of sociality1, and evolutionary theory predicts that these benefits need to arise at very small group sizes2. Such benefits are thought to emerge partly from scaling effects that increase efficiency as group size increases3-5. In social insects and other taxa, the benefits of group living have been proposed to stem from division of labour5-8, which is characterized by between-individual variability and within-individual consistency (specialization) in task performance. However, at the onset of sociality groups were probably small and composed of similar individuals with potentially redundant-rather than complementary-function1. Self-organization theory suggests that division of labour can emerge even in relatively small, simple groups9,10. However, empirical data on the effects of group size on division of labour and on fitness remain equivocal6. Here we use long-term automated behavioural tracking in clonal ant colonies, combined with mathematical modelling, to show that increases in the size of social groups can generate division of labour among extremely similar workers, in groups as small as six individuals. These early effects on behaviour were associated with large increases in homeostasis-the maintenance of stable conditions in the colony11-and per capita fitness. Our model suggests that increases in homeostasis are primarily driven by increases in group size itself, and to a smaller extent by a higher division of labour. Our results indicate that division of labour, increased homeostasis and higher fitness can emerge naturally in social groups that are small and homogeneous, and that scaling effects associated with increasing group size can thus promote social cohesion at the incipient stages of group living.}, } @article {pmid30135540, year = {2018}, author = {Warren, M}, title = {Mum's a Neanderthal, Dad's a Denisovan: First discovery of an ancient-human hybrid.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {417-418}, doi = {10.1038/d41586-018-06004-0}, pmid = {30135540}, issn = {1476-4687}, } @article {pmid30135539, year = {2018}, author = {Reardon, S}, title = {Hurricane Maria's wrath leaves clues to coral reefs' future.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {421-422}, doi = {10.1038/d41586-018-06014-y}, pmid = {30135539}, issn = {1476-4687}, mesh = {Animals ; Anthozoa/*physiology ; *Coral Reefs ; *Cyclonic Storms ; *Global Warming ; Puerto Rico ; }, } @article {pmid30135538, year = {2018}, author = {}, title = {Dark-energy telescope, asteroid hunters and gene-therapy rules.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {414-415}, doi = {10.1038/d41586-018-05983-4}, pmid = {30135538}, issn = {1476-4687}, } @article {pmid30135537, year = {2018}, author = {Teytelman, L}, title = {No more excuses for non-reproducible methods.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {411}, doi = {10.1038/d41586-018-06008-w}, pmid = {30135537}, issn = {1476-4687}, } @article {pmid30135536, year = {2018}, author = {Masood, E}, title = {The battle for the soul of biodiversity.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {423-425}, doi = {10.1038/d41586-018-05984-3}, pmid = {30135536}, issn = {1476-4687}, mesh = {*Administrative Personnel ; Animals ; *Biodiversity ; *Consensus ; Conservation of Natural Resources/economics/*legislation & jurisprudence ; Ecology/economics/legislation & jurisprudence ; *Extinction, Biological ; Global Warming/legislation & jurisprudence/prevention & control ; Human Activities ; Internationality ; Plants ; Politics ; Research Personnel ; Research Report ; }, } @article {pmid30135534, year = {2018}, author = {Conticello, S}, title = {Scientists informing policy should disclose their own beliefs.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {431}, doi = {10.1038/d41586-018-06017-9}, pmid = {30135534}, issn = {1476-4687}, mesh = {Abortion, Induced ; Argentina ; Female ; Humans ; *Policy ; Pregnancy ; *Science ; }, } @article {pmid30135533, year = {2018}, author = {Akabayashi, A and Nakazawa, E and Jecker, NS}, title = {Japan must tighten up clinical trial of stem cells for heart failure.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {431}, doi = {10.1038/d41586-018-06015-x}, pmid = {30135533}, issn = {1476-4687}, mesh = {Adult Stem Cells/cytology/*transplantation ; Cellular Reprogramming ; Clinical Trials as Topic/ethics/*standards ; Compassionate Use Trials/ethics/standards ; Heart Failure/pathology/surgery/*therapy ; Humans ; Induced Pluripotent Stem Cells/cytology/*transplantation ; Japan ; Myocytes, Cardiac/cytology/transplantation ; Patient Safety ; }, } @article {pmid30135532, year = {2018}, author = {Ali, T and Xie, W}, title = {Why Pakistan needs more reservoirs, and fast.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {431}, doi = {10.1038/d41586-018-06016-w}, pmid = {30135532}, issn = {1476-4687}, mesh = {China ; Federal Government ; Pakistan ; *Politics ; Time Factors ; Water Supply/*statistics & numerical data ; }, } @article {pmid30135531, year = {2018}, author = {Heron, JT and Mundy, JA}, title = {Electric and magnetic domains inverted by a magnetic field.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {435-436}, doi = {10.1038/d41586-018-05982-5}, pmid = {30135531}, issn = {1476-4687}, } @article {pmid30135530, year = {2018}, author = {Troyer, M}, title = {Topological phenomena explored in a programmable quantum simulation.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {438-439}, doi = {10.1038/d41586-018-05979-0}, pmid = {30135530}, issn = {1476-4687}, mesh = {*Quantum Theory ; }, } @article {pmid30135529, year = {2018}, author = {Leo, N and Carolus, V and White, JS and Kenzelmann, M and Hudl, M and Tolédano, P and Honda, T and Kimura, T and Ivanov, SA and Weil, M and Lottermoser, T and Meier, D and Fiebig, M}, title = {Magnetoelectric inversion of domain patterns.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {466-470}, doi = {10.1038/s41586-018-0432-4}, pmid = {30135529}, issn = {1476-4687}, abstract = {The inversion of inhomogeneous physical states has great technological importance; for example, active noise reduction relies on the emission of an inverted sound wave that interferes destructively with the noise of the emitter1, and inverting the evolution of a spin system by using a magnetic-field pulse enables magnetic resonance tomography2. In contrast to these examples, inversion of a distribution of ferromagnetic or ferroelectric domains within a material is surprisingly difficult: field poling creates a single-domain state, and piece-by-piece inversion using a scanning tip is impractical. Here we report inversion of entire ferromagnetic and ferroelectric domain patterns in the magnetoelectric material Co3TeO6 and the multiferroic material Mn2GeO4, respectively. In these materials, an applied magnetic field reverses the magnetization or polarization, respectively, of each domain, but leaves the domain pattern intact. Landau theory indicates that this type of magnetoelectric inversion is universal across materials that exhibit complex ordering, with one order parameter holding the memory of the domain structure and another setting its overall sign. Domain-pattern inversion is only one example of a previously unnoticed effect in systems such as multiferroics, in which several order parameters are available for combination. Exploring these effects could therefore advance multiferroics towards new levels of functionality.}, } @article {pmid30135528, year = {2018}, author = {Stützer, S and Plotnik, Y and Lumer, Y and Titum, P and Lindner, NH and Segev, M and Rechtsman, MC and Szameit, A}, title = {Photonic topological Anderson insulators.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {461-465}, doi = {10.1038/s41586-018-0418-2}, pmid = {30135528}, issn = {1476-4687}, support = {DMS-1620422//National Science Foundation/International ; }, abstract = {The hallmark property of two-dimensional topological insulators is robustness of quantized electronic transport of charge and energy against disorder in the underlying lattice1. That robustness arises from the fact that, in the topological bandgap, such transport can occur only along the edge states, which are immune to backscattering owing to topological protection. However, for sufficiently strong disorder, this bandgap closes and the system as a whole becomes topologically trivial: all states are localized and all transport vanishes in accordance with Anderson localization2,3. The recent suggestion4 that the reverse transition can occur was therefore surprising. In so-called topological Anderson insulators, it has been predicted4 that the emergence of protected edge states and quantized transport can be induced, rather than inhibited, by the addition of sufficient disorder to a topologically trivial insulator. Here we report the experimental demonstration of a photonic topological Anderson insulator. Our experiments are carried out in an array of helical evanescently coupled waveguides in a honeycomb geometry with detuned sublattices. Adding on-site disorder in the form of random variations in the refractive index of the waveguides drives the system from a trivial phase into a topological one. This manifestation of topological Anderson insulator physics shows experimentally that disorder can enhance transport rather than arrest it.}, } @article {pmid30135527, year = {2018}, author = {King, AD and Carrasquilla, J and Raymond, J and Ozfidan, I and Andriyash, E and Berkley, A and Reis, M and Lanting, T and Harris, R and Altomare, F and Boothby, K and Bunyk, PI and Enderud, C and Fréchette, A and Hoskinson, E and Ladizinsky, N and Oh, T and Poulin-Lamarre, G and Rich, C and Sato, Y and Smirnov, AY and Swenson, LJ and Volkmann, MH and Whittaker, J and Yao, J and Ladizinsky, E and Johnson, MW and Hilton, J and Amin, MH}, title = {Observation of topological phenomena in a programmable lattice of 1,800 qubits.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {456-460}, doi = {10.1038/s41586-018-0410-x}, pmid = {30135527}, issn = {1476-4687}, abstract = {The work of Berezinskii, Kosterlitz and Thouless in the 1970s1,2 revealed exotic phases of matter governed by the topological properties of low-dimensional materials such as thin films of superfluids and superconductors. A hallmark of this phenomenon is the appearance and interaction of vortices and antivortices in an angular degree of freedom-typified by the classical XY model-owing to thermal fluctuations. In the two-dimensional Ising model this angular degree of freedom is absent in the classical case, but with the addition of a transverse field it can emerge from the interplay between frustration and quantum fluctuations. Consequently, a Kosterlitz-Thouless phase transition has been predicted in the quantum system-the two-dimensional transverse-field Ising model-by theory and simulation3-5. Here we demonstrate a large-scale quantum simulation of this phenomenon in a network of 1,800 in situ programmable superconducting niobium flux qubits whose pairwise couplings are arranged in a fully frustrated square-octagonal lattice. Essential to the critical behaviour, we observe the emergence of a complex order parameter with continuous rotational symmetry, and the onset of quasi-long-range order as the system approaches a critical temperature. We describe and use a simple approach to statistical estimation with an annealing-based quantum processor that performs Monte Carlo sampling in a chain of reverse quantum annealing protocols. Observations are consistent with classical simulations across a range of Hamiltonian parameters. We anticipate that our approach of using a quantum processor as a programmable magnetic lattice will find widespread use in the simulation and development of exotic materials.}, } @article {pmid30135526, year = {2018}, author = {Li, C and Fraser, NC and Rieppel, O and Wu, XC}, title = {A Triassic stem turtle with an edentulous beak.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {476-479}, doi = {10.1038/s41586-018-0419-1}, pmid = {30135526}, issn = {1476-4687}, mesh = {Animals ; Beak/*anatomy & histology ; China ; Fossils ; *Phylogeny ; Turtles/*anatomy & histology/*classification ; }, abstract = {The early evolution of turtles continues to be a contentious issue in vertebrate palaeontology. Recent reports have suggested that they are diapsids1-6, but the position of turtles within Diapsida is controversial7-12 and the sequence of acquisition of turtle synapomorphies remains unclear1-3. Here we describe a Triassic turtle from China that has a mixture of derived characters and plesiomorphic features. To our knowledge, it represents the earliest known stem turtle with an edentulous beak and a rigid puboischiadic plate. The discovery of this new form reveals a complex early history of turtles.}, } @article {pmid30135501, year = {2018}, author = {Nielsen, C and Brunet, T and Arendt, D}, title = {Evolution of the bilaterian mouth and anus.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1358-1376}, doi = {10.1038/s41559-018-0641-0}, pmid = {30135501}, issn = {2397-334X}, abstract = {It is widely held that the bilaterian tubular gut with mouth and anus evolved from a simple gut with one major gastric opening. However, there is no consensus on how this happened. Did the single gastric opening evolve into a mouth, with the anus forming elsewhere in the body (protostomy), or did it evolve into an anus, with the mouth forming elsewhere (deuterostomy), or did it evolve into both mouth and anus (amphistomy)? These questions are addressed by the comparison of developmental fates of the blastopore, the opening of the embryonic gut, in diverse animals that live today. Here we review comparative data on the identity and fate of blastoporal tissue, investigate how the formation of the through-gut relates to the major body axes, and discuss to what extent evolutionary scenarios are consistent with these data. Available evidence indicates that stem bilaterians had a slit-like gastric opening that was partially closed in subsequent evolution, leaving open the anus and most likely also the mouth, which would favour amphistomy. We discuss remaining difficulties, and outline directions for future research.}, } @article {pmid30135477, year = {2018}, author = {Koch, L}, title = {In vivo lineage tracing in mice.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {669}, doi = {10.1038/s41576-018-0048-4}, pmid = {30135477}, issn = {1471-0064}, } @article {pmid30135103, year = {2018}, author = {Roberts, J and Childerhouse, S and Roe, W and Baker, GB and Hamilton, S}, title = {No evidence of cryptic bycatch causing New Zealand sea lion population decline.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8330-E8331}, pmid = {30135103}, issn = {1091-6490}, mesh = {Animals ; *Fisheries ; New Zealand ; *Sea Lions ; }, } @article {pmid30135102, year = {2018}, author = {Meyer, S and Robertson, BC and Chilvers, BL and Krkošek, M}, title = {Reply to Roberts et al.: Faith in no fishery impact on New Zealand sea lions based on misunderstandings and unsubstantiated claims.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8332}, pmid = {30135102}, issn = {1091-6490}, mesh = {Animals ; *Fisheries ; New Zealand ; *Sea Lions ; }, } @article {pmid30135101, year = {2018}, author = {Woodward, MA and Sitti, M}, title = {Morphological intelligence counters foot slipping in the desert locust and dynamic robots.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8358-E8367}, pmid = {30135101}, issn = {1091-6490}, mesh = {Animals ; Biomechanical Phenomena ; Grasshoppers/*anatomy & histology/*physiology ; *Robotics ; }, abstract = {During dynamic terrestrial locomotion, animals use complex multifunctional feet to extract friction from the environment. However, whether roboticists assume sufficient surface friction for locomotion or actively compensate for slipping, they use relatively simple point-contact feet. We seek to understand and extract the morphological adaptations of animal feet that contribute to enhancing friction on diverse surfaces, such as the desert locust (Schistocerca gregaria) [Bennet-Clark HC (1975) J Exp Biol 63:53-83], which has both wet adhesive pads and spines. A buckling region in their knee to accommodate slipping [Bayley TG, Sutton GP, Burrows M (2012) J Exp Biol 215:1151-1161], slow nerve conduction velocity (0.5-3 m/s) [Pearson KG, Stein RB, Malhotra SK (1970) J Exp Biol 53:299-316], and an ecological pressure to enhance jumping performance for survival [Hawlena D, Kress H, Dufresne ER, Schmitz OJ (2011) Funct Ecol 25:279-288] further suggest that the locust operates near the limits of its surface friction, but without sufficient time to actively control its feet. Therefore, all surface adaptation must be through passive mechanics (morphological intelligence), which are unknown. Here, we report the slipping behavior, dynamic attachment, passive mechanics, and interplay between the spines and adhesive pads, studied through both biological and robotic experiments, which contribute to the locust's ability to jump robustly from diverse surfaces. We found slipping to be surface-dependent and common (e.g., wood 1.32 ± 1.19 slips per jump), yet the morphological intelligence of the feet produces a significant chance to reengage the surface (e.g., wood 1.10 ± 1.13 reengagements per jump). Additionally, a discovered noncontact-type jump, further studied robotically, broadens the applicability of the morphological adaptations to both static and dynamic attachment.}, } @article {pmid30135100, year = {2018}, author = {Newby, JM and Schaefer, AM and Lee, PT and Forest, MG and Lai, SK}, title = {Convolutional neural networks automate detection for tracking of submicron-scale particles in 2D and 3D.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {9026-9031}, pmid = {30135100}, issn = {1091-6490}, support = {R41 GM123897/GM/NIGMS NIH HHS/United States ; }, mesh = {Automation ; *Machine Learning ; *Nanoparticles ; *Neural Networks (Computer) ; Particle Size ; *Video Recording ; }, abstract = {Particle tracking is a powerful biophysical tool that requires conversion of large video files into position time series, i.e., traces of the species of interest for data analysis. Current tracking methods, based on a limited set of input parameters to identify bright objects, are ill-equipped to handle the spectrum of spatiotemporal heterogeneity and poor signal-to-noise ratios typically presented by submicron species in complex biological environments. Extensive user involvement is frequently necessary to optimize and execute tracking methods, which is not only inefficient but introduces user bias. To develop a fully automated tracking method, we developed a convolutional neural network for particle localization from image data, comprising over 6,000 parameters, and used machine learning techniques to train the network on a diverse portfolio of video conditions. The neural network tracker provides unprecedented automation and accuracy, with exceptionally low false positive and false negative rates on both 2D and 3D simulated videos and 2D experimental videos of difficult-to-track species.}, } @article {pmid30135099, year = {2018}, author = {DeCoursey, TE}, title = {Gating currents indicate complex gating of voltage-gated proton channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9057-9059}, pmid = {30135099}, issn = {1091-6490}, support = {R01 GM121462/GM/NIGMS NIH HHS/United States ; R35 GM126902/GM/NIGMS NIH HHS/United States ; }, mesh = {*Ion Channel Gating ; Ion Channels ; Patch-Clamp Techniques ; *Protons ; }, } @article {pmid30135098, year = {2018}, author = {Lepot, S and Aumaître, S and Gallet, B}, title = {Radiative heating achieves the ultimate regime of thermal convection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8937-8941}, pmid = {30135098}, issn = {1091-6490}, abstract = {The absorption of light or radiation drives turbulent convection inside stars, supernovae, frozen lakes, and Earth's mantle. In these contexts, the goal of laboratory and numerical studies is to determine the relation between the internal temperature gradients and the heat flux transported by the turbulent flow. This is the constitutive law of turbulent convection, to be input into large-scale models of such natural flows. However, in contrast with the radiative heating of natural flows, laboratory experiments have focused on convection driven by heating and cooling plates; the heat transport is then severely restricted by boundary layers near the plates, which prevents the realization of the mixing length scaling law used in evolution models of geophysical and astrophysical flows. There is therefore an important discrepancy between the scaling laws measured in laboratory experiments and those used, e.g., in stellar evolution models. Here we provide experimental and numerical evidence that radiatively driven convection spontaneously achieves the mixing length scaling regime, also known as the "ultimate" regime of thermal convection. This constitutes a clear observation of this regime of turbulent convection. Our study therefore bridges the gap between models of natural flows and laboratory experiments. It opens an experimental avenue for a priori determinations of the constitutive laws to be implemented into models of geophysical and astrophysical flows, as opposed to empirical fits of these constitutive laws to the scarce observational data.}, } @article {pmid30134972, year = {2018}, author = {Ziganshina, EE and Mohammed, WS and Shagimardanova, EI and Shigapova, LH and Ziganshin, AM}, title = {Draft genome sequence of Bacillus pumilus strain EZ-C07 isolated from digested agricultural wastes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {606}, pmid = {30134972}, issn = {1756-0500}, support = {16-34-60093//Russian Foundation for Basic Research/ ; }, mesh = {Bacillus pumilus/*genetics ; DNA, Bacterial ; Hydrogen Peroxide ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Sequence Analysis, DNA ; }, abstract = {OBJECTIVES: Bacillus species, belonging to the family Bacillaceae, are rod-shaped aerobic or facultative anaerobic Gram-positive bacteria that can be isolated from various environmental niches. Bacillus pumilus strains are resistant to unfavorable conditions such as UV, H2O2 and chemical disinfection. Furthermore, B. pumilus strains synthesize multifarious important enzymes and can be used in the production of some fermented foods, bioremediation of wastewater systems and biodegradation of environmental contaminants. Hence, investigation at the genomic level is required to understand their ecology, genetics and potential applications.

DATA DESCRIPTION: In this research, we provide the genomic insights into one Bacillus species (EZ-C07) isolated from digested agricultural waste materials. The draft genome of the strain EZ-C07 consists of 3,724,869 bp with 3890 coding sequences and 41.5% G + C content. Based on 16S rRNA gene sequence analysis followed by in silico DNA-DNA hybridization studies, the strain EZ-C07 was identified as Bacillus pumilus belonging to the family Bacillaceae within the phylum Firmicutes. The whole genome shotgun project of B. pumilus strain EZ-C07 can be accessed at DDBJ/ENA/GenBank under the Accession QLVI00000000.}, } @article {pmid30134970, year = {2018}, author = {Habte, L and Tadesse, E and Ferede, G and Amsalu, A}, title = {Typhoid fever: clinical presentation and associated factors in febrile patients visiting Shashemene Referral Hospital, southern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {605}, pmid = {30134970}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Referral and Consultation ; Salmonella typhi ; Typhoid Fever/complications/*diagnosis/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Although typhoid fever is a major public health problem in Ethiopia, data is not available in the study area. Therefore, this study aimed to determine the prevalence, clinical presentation at the time of diagnosis and associated factors of typhoid fever among febrile patients visiting Shashemene Referral Hospital, southern Ethiopia. A cross-sectional study was conducted from January 1, 2016, to October 30, 2016. Socio-demographic and clinical data were collected using a structured questionnaire. A blood sample was collected and inoculated into Tryptic soy broth.

RESULTS: A total of 421 adult febrile patients suspected of typhoid fever were included in the study. Of these, the overall prevalence of culture-confirmed typhoid fever was 5.0% (21/421). The prevalence of typhoid fever was significantly associated with rural residence (8.4%). As compared to the urban resident, the rural resident was 3.6 times more likely found to have culture-confirmed typhoid fever. The prevalence of typhoid fever was significantly associated with those patients whose water source was spring 7 (12.3%) and river 7 (13.2%). All of those study participants who used treated water were culture negative. Fever for ≥ 5 days, abdominal pain, and skin rash independently predicted blood culture-confirmed typhoid fever.}, } @article {pmid30134926, year = {2018}, author = {Hua, BL and Bell, GW and Kashevsky, H and Von Stetina, JR and Orr-Weaver, TL}, title = {Dynamic changes in ORC localization and replication fork progression during tissue differentiation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {623}, pmid = {30134926}, issn = {1471-2164}, support = {HG004279//National Human Genome Research Institute/ ; U01 HG004279/HG/NHGRI NIH HHS/United States ; GM118098//National Institute of General Medical Sciences/ ; GM57940//National Institute of General Medical Sciences/ ; R35 GM118098/GM/NIGMS NIH HHS/United States ; R01 GM057960/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; Cell Differentiation/*genetics ; *Chromosome Structures/chemistry/genetics/metabolism ; DNA Replication/*genetics ; Drosophila melanogaster/embryology/genetics ; Embryo, Nonmammalian ; Larva ; Organ Specificity/genetics ; Organogenesis/*genetics ; Origin Recognition Complex/*metabolism ; Replication Origin/*physiology ; }, abstract = {BACKGROUND: Genomic regions repressed for DNA replication, resulting in either delayed replication in S phase or underreplication in polyploid cells, are thought to be controlled by inhibition of replication origin activation. Studies in Drosophila polytene cells, however, raised the possibility that impeding replication fork progression also plays a major role.

RESULTS: We exploited genomic regions underreplicated (URs) with tissue specificity in Drosophila polytene cells to analyze mechanisms of replication repression. By localizing the Origin Recognition Complex (ORC) in the genome of the larval fat body and comparing this to ORC binding in the salivary gland, we found that sites of ORC binding show extensive tissue specificity. In contrast, there are common domains nearly devoid of ORC in the salivary gland and fat body that also have reduced density of ORC binding sites in diploid cells. Strikingly, domains lacking ORC can still be replicated in some polytene tissues, showing absence of ORC and origins is insufficient to repress replication. Analysis of the width and location of the URs with respect to ORC position indicates that whether or not a genomic region lacking ORC is replicated is controlled by whether replication forks formed outside the region are inhibited.

CONCLUSIONS: These studies demonstrate that inhibition of replication fork progression can block replication across genomic regions that constitutively lack ORC. Replication fork progression can be inhibited in both tissue-specific and genome region-specific ways. Consequently, when evaluating sources of genome instability it is important to consider altered control of replication forks in response to differentiation.}, } @article {pmid30134911, year = {2018}, author = {Babaian, A and Ebou, A and Fegen, A and Kam, HY and Novakovsky, GE and Wong, J and Aïssi, D and Yao, L}, title = {bioSyntax: syntax highlighting for computational biology.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {303}, pmid = {30134911}, issn = {1471-2105}, support = {140//Faculty of Medicine, University of British Columbia/ ; }, mesh = {*Computational Biology ; Information Storage and Retrieval ; Nucleotides/genetics ; Sequence Alignment ; *Software ; }, abstract = {BACKGROUND: Computational biology requires the reading and comprehension of biological data files. Plain-text formats such as SAM, VCF, GTF, PDB and FASTA, often contain critical information which is obfuscated by the data structure complexity.

RESULTS: bioSyntax (https://biosyntax.org/) is a freely available suite of biological syntax highlighting packages for vim, gedit, Sublime, VSCode, and less. bioSyntax improves the legibility of low-level biological data in the bioinformatics workspace.

CONCLUSION: bioSyntax supports computational scientists in parsing and comprehending their data efficiently and thus can accelerate research output.}, } @article {pmid30134875, year = {2018}, author = {Wu, X and Xu, H and Liu, G and Zhao, L and Mu, C}, title = {Effects of permafrost collapse on soil bacterial communities in a wet meadow on the northern Qinghai-Tibetan Plateau.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {27}, pmid = {30134875}, issn = {1472-6785}, support = {41721091//National Natural Science Foundation of China/International ; 41661013//National Natural Science Foundation of China/International ; 41871060//National Natural Science Foundation of China/International ; 41601063//National Natural Science Foundation of China/International ; }, abstract = {BACKGROUND: Permafrost degradation may develop thermokarst landforms, which substantially change physico-chemical characteristics in the soil as well as the soil carbon stock. However, little is known about changes of bacterial community among the microfeatures within thermokarst area.

RESULTS: We investigated bacterial communities using the Illumina sequencing method and examined their relationships with soil parameters in a thermokarst feature on the northern Qinghai-Tibetan Plateau. We categorized the ground surface into three different micro-relief patches based on the type and extent of permafrost collapse (control, collapsing and subsided areas). Permafrost collapse significantly decreased the soil carbon density and moisture content in the upper 10 cm samples in the collapsing areas. The highest loading factors for the first principal component (PC) extracted from the soil parameters were soil carbon and nitrogen contents, while soil moisture content and C:N ratios were the highest loading factors for the second PC. The relative abundance of Acidobacteria decreased with depth. Bacterial diversity in subsided areas was higher than that in control areas.

CONCLUSIONS: Bacterial community structure was significantly affected by pH and depth. The relative abundance of Gemmatimonadetes and Firmicutes were significantly correlated with the first and second PCs extracted from multiple soil parameters, suggesting these phyla could be used as indicators for the soil parameters in the thermokarst terrain.}, } @article {pmid30134843, year = {2018}, author = {Sargsyan, E and Cen, J and Roomp, K and Schneider, R and Bergsten, P}, title = {Identification of early biological changes in palmitate-treated isolated human islets.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {629}, pmid = {30134843}, issn = {1471-2164}, support = {279 153//European Commission FP7/ ; }, mesh = {Adult ; Cells, Cultured ; Female ; Gene Expression Profiling ; Gene Expression Regulation/drug effects ; Humans ; Insulin/metabolism ; Insulin-Secreting Cells/drug effects/physiology ; Islets of Langerhans/*drug effects/physiology ; Male ; Microarray Analysis ; Middle Aged ; Palmitic Acid/*pharmacology ; Primary Cell Culture ; Time Factors ; Transcriptome/drug effects ; }, abstract = {BACKGROUND: Long-term exposure to elevated levels of free fatty acids (FFAs) is deleterious for beta-cell function and may contribute to development of type 2 diabetes mellitus (T2DM). Whereas mechanisms of impaired glucose-stimulated insulin secretion (GSIS) in FFA-treated beta-cells have been intensively studied, biological events preceding the secretory failure, when GSIS is accentuated, are poorly investigated. To identify these early events, we performed genome-wide analysis of gene expression in isolated human islets exposed to fatty acid palmitate for different time periods.

RESULTS: Palmitate-treated human islets showed decline in beta-cell function starting from day two. Affymetrix Human Transcriptome Array 2.0 identified 903 differentially expressed genes (DEGs). Mapping of the genes onto pathways using KEGG pathway enrichment analysis predicted four islet biology-related pathways enriched prior but not after the decline of islet function and three pathways enriched both prior and after the decline of islet function. DEGs from these pathways were analyzed at the transcript level. The results propose that in palmitate-treated human islets, at early time points, protective events, including up-regulation of metallothioneins, tRNA synthetases and fatty acid-metabolising proteins, dominate over deleterious events, including inhibition of fatty acid detoxification enzymes, which contributes to the enhanced GSIS. After prolonged exposure of islets to palmitate, the protective events are outweighed by the deleterious events, which leads to impaired GSIS.

CONCLUSIONS: The study identifies temporal order between different cellular events, which either promote or protect from beta-cell failure. The sequence of these events should be considered when developing strategies for prevention and treatment of the disease.}, } @article {pmid30134841, year = {2018}, author = {Almiñana, C and Tsikis, G and Labas, V and Uzbekov, R and da Silveira, JC and Bauersachs, S and Mermillod, P}, title = {Deciphering the oviductal extracellular vesicles content across the estrous cycle: implications for the gametes-oviduct interactions and the environment of the potential embryo.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {622}, pmid = {30134841}, issn = {1471-2164}, support = {n° 267196.//EU Marie-Curie FP7 COFUND People Programme, AgreenSkills fellowship/ ; no.3569//SMHARTproject, by the European Regional Development Fund (ERDF), the Conseil Régional du Centre, the French National Institute for Agricultural Research (INRA) and the French National Institute of Health and Medical Research (Inserm)./ ; }, mesh = {Animals ; Cattle ; Cell Communication/genetics ; Cellular Microenvironment/genetics ; Embryo, Mammalian/cytology ; Embryonic Development/genetics ; Estrous Cycle/*genetics/*metabolism ; Extracellular Vesicles/chemistry/*genetics/*metabolism ; Fallopian Tubes/metabolism/*ultrastructure ; Female ; Germ Cells/*metabolism/physiology ; Male ; MicroRNAs/metabolism ; Ovum Transport/genetics ; Proteins/analysis/genetics/metabolism ; Sperm Transport/genetics ; }, abstract = {BACKGROUND: The success of early reproductive events depends on an appropriate communication between gametes/embryos and the oviduct. Extracellular vesicles (EVs) contained in oviductal secretions have been suggested as new players in mediating this crucial cross-talk by transferring their cargo (proteins, mRNA and small ncRNA) from cell to cell. However, little is known about the oviductal EVs (oEVS) composition and their implications in the reproductive success. The aim of the study was to determine the oEVs content at protein, mRNA and small RNA level and to examine whether the oEVs content is under the hormonal influence of the estrous cycle.

RESULTS: We identified the presence of oEVs, exosomes and microvesicles, in the bovine oviductal fluid at different stages of the estrous cycle (postovulatory-stage, early luteal phase, late luteal phase and pre-ovulatory stage) and demonstrated that their composition is under hormonal regulation. RNA-sequencing identified 903 differentially expressed transcripts (FDR < 0.001) in oEVs across the estrous cycle. Moreover, small RNA-Seq identified the presence of different types of ncRNAs (miRNAs, rRNA fragments, tRNA fragments, snRNA, snoRNA, and other ncRNAs), which were partially also under hormonal influence. Major differences were found between post-ovulatory and the rest of the stages analyzed for mRNAs. Interesting miRNAs identified in oEVs and showing differential abundance among stages, miR-34c and miR-449a, have been associated with defective cilia in the oviduct and infertility. Furthermore, functional annotation of the differentially abundant mRNAs identified functions related to exosome/vesicles, cilia expression, embryo development and many transcripts encoding ribosomal proteins. Moreover, the analysis of oEVs protein content also revealed changes across the estrous cycle. Mass spectrometry identified 336 clusters of proteins in oEVs, of which 170 were differentially abundant across the estrous cycle (p-value< 0.05, ratio < 0.5 or ratio > 2). Our data revealed proteins related to early embryo development and gamete-oviduct interactions as well as numerous ribosomal proteins.

CONCLUSIONS: Our study provides with the first molecular signature of oEVs across the bovine estrous cycle, revealing marked differences between post- and pre-ovulatory stages. Our findings contribute to a better understanding of the potential role of oEVs as modulators of gamete/embryo-maternal interactions and their implications for the reproductive success.}, } @article {pmid30134839, year = {2018}, author = {Li, C and Wang, J and Song, K and Meng, J and Xu, F and Li, L and Zhang, G}, title = {Construction of a high-density genetic map and fine QTL mapping for growth and nutritional traits of Crassostrea gigas.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {626}, pmid = {30134839}, issn = {1471-2164}, support = {31530079//National Natural Science Foundation of China/ ; 31572620//National Natural Science Foundation of China/ ; CARS-49//Earmarked Fund for Modern Agro-industry Technology Research System/ ; XDA586 11020305//Strategic Priority Research Program of "Western Pacific Ocean System: Structure, Dynamics and Consequences"/ ; }, mesh = {Animal Nutritional Physiological Phenomena/*genetics ; Animals ; Chromosome Mapping/*methods ; Crassostrea/*genetics/growth & development/*physiology ; Genetic Association Studies ; Genetic Linkage ; Genetic Markers ; Phenotype ; *Quantitative Trait Loci ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Both growth and nutritional traits are important economic traits of Crassostrea gigas (C. gigas) in industry. But few work has been done to study the genetic architecture of nutritional traits of the oyster. In this study, we constructed a high-density genetic map of C. gigas to help assemble the genome sequence onto chromosomes, meanwhile explore the genetic basis for nutritional traits via quantitative trait loci (QTL) mapping.

RESULTS: The constructed genetic map contained 5024 evenly distributed markers, with an average marker interval of 0.68 cM, thus representing the densest genetic map produced for the oyster. According to the high collinearity between the consensus map and the oyster genome, 1574 scaffold (about 70%) of the genome sequence of C. gigas were successfully anchored to 10 linkage groups (LGs) of the consensus map. Using this high-qualified genetic map, we then conducted QTL analysis for growth and nutritional traits, the latter of which includes glycogen, amino acid (AA), and fatty acid (FA). Overall, 41 QTLs were detected for 17 traits. In addition, six candidate genes identified in the QTL interval showed significant correlation with the traits on transcriptional levels. These genes include growth-related genes AMY and BMP1, AA metabolism related genes PLSCR and GR, and FA metabolism regulation genes DYRK and ADAMTS.

CONCLUSION: Using the constructed high-qualified linkage map, this study not only assembled nearly 70% of the oyster genome sequence onto chromosomes, but also identified valuable markers and candidate genes for growth and nutritional traits, especially for AA and FA that undergone few studies before. These findings will facilitate genome assembly and molecular breeding of important economic traits in C. gigas.}, } @article {pmid30134836, year = {2018}, author = {Liu, C and Fan, D and Li, Y and Chen, Y and Huang, L and Yan, X}, title = {Transcriptome analysis of Valsa mali reveals its response mechanism to the biocontrol actinomycete Saccharothrix yanglingensis Hhs.015.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {90}, pmid = {30134836}, issn = {1471-2180}, abstract = {BACKGROUND: Apple canker is a devastating branch disease caused by Valsa mali (Vm). The endophytic actinomycete Saccharothrix yanglingensis Hhs.015 (Sy Hhs.015) can effectively inhibit the growth of Vm. To reveal the mechanism, by which Vm respond to Sy Hhs.015, the transcriptome of Vm was analyzed using RNA-seq technology.

RESULTS: Compared with normal growing Vm in the control group, 1476 genes were significantly differentially expressed in the Sy Hhs.015's treatment group, of which 851 genes were up-regulated and 625 genes were down-regulated. Combined gene function and pathway analysis of differentially expressed genes (DEGs) revealed that Sy Hhs.015 affected the carbohydrate metabolic pathway, which is utilized by Vm for energy production. Approximately 82% of the glycoside hydrolase genes were down-regulated, including three pectinase genes (PGs), which are key pathogenic factors. The cell wall structure of Vm was disrupted by Sy Hhs.015 and cell wall-related genes were found to be down-regulated. Of the peroxisome associated genes, those encoding catalase (CAT) and superoxide dismutase (SOD) which scavenge reactive oxygen species (ROS), as well as those encoding AMACR and ACAA1 which are related to the β-oxidation of fatty acids, were down-regulated. MS and ICL, key genes in glyoxylate cycle, were also down-regulated. In response to the stress of Sy Hhs.015 exposure, Vm increased amino acid metabolism to synthesize the required nitrogenous compounds, while alpha-keto acids, which involved in the TCA cycle, could be used to produce energy by deamination or transamination. Retinol dehydrogenase, associated with cell wall dextran synthesis, and sterol 24-C-methyltransferase, related to cell membrane ergosterol synthesis, were up-regulated. The genes encoding glutathione S-transferase, (GST), which has antioxidant activity and ABC transporters which have an efflux function, were also up-regulated.

CONCLUSION: These results show that the response of Vm to Sy Hhs.015 exposure is a complicated and highly regulated process, and provide a theoretical basis for both clarifying the biocontrol mechanism of Sy Hhs.015 and the response of Vm to stress.}, } @article {pmid30134835, year = {2018}, author = {Cho, BC and Hardies, SC and Jang, GI and Hwang, CY}, title = {Complete genome of streamlined marine actinobacterium Pontimonas salivibrio strain CL-TW6T adapted to coastal planktonic lifestyle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {625}, pmid = {30134835}, issn = {1471-2164}, mesh = {Actinomycetales/*genetics/*growth & development ; Adaptation, Biological/*genetics ; Aquatic Organisms/genetics/growth & development ; Bacterial Typing Techniques ; DNA, Bacterial/analysis/genetics ; Ecosystem ; Estuaries ; Genome, Bacterial ; Phylogeny ; Plankton/genetics/growth & development ; *Seawater ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Pontimonas salivibrio strain CL-TW6T (=KCCM 90105 = JCM18206) was characterized as the type strain of a new genus within the Actinobacterial family Microbacteriaceae. It was isolated from a coastal marine environment in which members of Microbactericeae have not been previously characterized.

RESULTS: The genome of P. salivibrio CL-TW6T was a single chromosome of 1,760,810 bp. Genomes of this small size are typically found in bacteria growing slowly in oligotrophic zones and said to be streamlined. Phylogenetic analysis showed it to represent a lineage originating in the Microbacteriaceae radiation occurring before the snowball Earth glaciations, and to have a closer relationship with some streamlined bacteria known through metagenomic data. Several genomic characteristics typical of streamlined bacteria are found: %G + C is lower than non-streamlined members of the phylum; there are a minimal number of rRNA and tRNA genes, fewer paralogs in most gene families, and only two sigma factors; there is a noticeable absence of some nonessential metabolic pathways, including polyketide synthesis and catabolism of some amino acids. There was no indication of any phage genes or plasmids, however, a system of active insertion elements was present. P. salivibrio appears to be unusual in having polyrhamnose-based cell wall oligosaccharides instead of mycolic acid or teichoic acid-based oligosaccharides. Oddly, it conducts sulfate assimilation apparently for sulfating cell wall components, but not for synthesizing amino acids. One gene family it has more of, rather than fewer of, are toxin/antitoxin systems, which are thought to down-regulate growth during nutrient deprivation or other stressful conditions.

CONCLUSIONS: Because of the relatively small number of paralogs and its relationship to the heavily characterized Mycobacterium tuberculosis, we were able to heavily annotate the genome of P. salivibrio CL-TW6T. Its streamlined status and relationship to streamlined metagenomic constructs makes it an important reference genome for study of the streamlining concept. The final evolutionary trajectory of CL-TW6 T was to adapt to growth in a non-oligotrophic coastal zone. To understand that adaptive process, we give a thorough accounting of gene content, contrasting with both oligotrophic streamlined bacteria and large genome bacteria, and distinguishing between genes derived by vertical and horizontal descent.}, } @article {pmid30134833, year = {2018}, author = {Morales-Hojas, R and Hinsley, M and Armean, IM and Silk, R and Harrup, LE and Gonzalez-Uriarte, A and Veronesi, E and Campbell, L and Nayduch, D and Saski, C and Tabachnick, WJ and Kersey, P and Carpenter, S and Fife, M}, title = {The genome of the biting midge Culicoides sonorensis and gene expression analyses of vector competence for bluetongue virus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {624}, pmid = {30134833}, issn = {1471-2164}, support = {BB/J016721/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Bluetongue/immunology/*transmission/virology ; Bluetongue virus/immunology/*physiology ; Ceratopogonidae/*genetics/immunology/*virology ; Evolution, Molecular ; Gene Expression Profiling ; *Genome, Insect ; Host-Pathogen Interactions/genetics/immunology ; Immunity, Innate/genetics ; *Insect Vectors/genetics/physiology ; Molecular Sequence Annotation ; Sequence Analysis, DNA ; Transcriptome/genetics ; }, abstract = {BACKGROUND: The new genomic technologies have provided novel insights into the genetics of interactions between vectors, viruses and hosts, which are leading to advances in the control of arboviruses of medical importance. However, the development of tools and resources available for vectors of non-zoonotic arboviruses remains neglected. Biting midges of the genus Culicoides transmit some of the most important arboviruses of wildlife and livestock worldwide, with a global impact on economic productivity, health and welfare. The absence of a suitable reference genome has hindered genomic analyses to date in this important genus of vectors. In the present study, the genome of Culicoides sonorensis, a vector of bluetongue virus (BTV) in the USA, has been sequenced to provide the first reference genome for these vectors. In this study, we also report the use of the reference genome to perform initial transcriptomic analyses of vector competence for BTV.

RESULTS: Our analyses reveal that the genome is 189 Mb, assembled in 7974 scaffolds. Its annotation using the transcriptomic data generated in this study and in a previous study has identified 15,612 genes. Gene expression analyses of C. sonorensis females infected with BTV performed in this study revealed 165 genes that were differentially expressed between vector competent and refractory females. Two candidate genes, glutathione S-transferase (gst) and the antiviral helicase ski2, previously recognized as involved in vector competence for BTV in C. sonorensis (gst) and repressing dsRNA virus propagation (ski2), were confirmed in this study.

CONCLUSIONS: The reference genome of C. sonorensis has enabled preliminary analyses of the gene expression profiles of vector competent and refractory individuals. The genome and transcriptomes generated in this study provide suitable tools for future research on arbovirus transmission. These provide a valuable resource for these vector lineage, which diverged from other major Dipteran vector families over 200 million years ago. The genome will be a valuable source of comparative data for other important Dipteran vector families including mosquitoes (Culicidae) and sandflies (Psychodidae), and together with the transcriptomic data can yield potential targets for transgenic modification in vector control and functional studies.}, } @article {pmid30134832, year = {2018}, author = {Francis, IP and Islam, EA and Gower, AC and Shaik-Dasthagirisaheb, YB and Gray-Owen, SD and Wetzler, LM}, title = {Murine host response to Neisseria gonorrhoeae upper genital tract infection reveals a common transcriptional signature, plus distinct inflammatory responses that vary between reproductive cycle phases.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {627}, pmid = {30134832}, issn = {1471-2164}, support = {R01 AI103400/AI/NIAID NIH HHS/United States ; T32 AI007309/AI/NIAID NIH HHS/United States ; 2R01AI103400-05//National Institute of Allergy and Infectious Diseases/ ; MOP-15499//Canadian Institutes of Health Research/Canada ; }, mesh = {Animals ; Disease Models, Animal ; Estrous Cycle/genetics/*physiology ; Female ; Gene Expression Profiling ; Gonorrhea/*genetics/immunology ; Host-Pathogen Interactions/*genetics/immunology ; Humans ; Inflammation/*genetics/physiopathology ; Mice ; Microarray Analysis ; *Neisseria gonorrhoeae/immunology ; Reproductive Tract Infections/*genetics/immunology/microbiology ; *Transcriptome ; }, abstract = {BACKGROUND: The emergence of fully antimicrobial resistant Neisseria gonorrhoeae has led global public health agencies to identify a critical need for next generation anti-gonococcal pharmaceuticals. The development and success of these compounds will rely upon valid pre-clinical models of gonorrhoeae infection. We recently developed and reported the first model of upper genital tract gonococcal infection. During initial characterization, we observed significant reproductive cycle-based variation in infection outcome. When uterine infection occurred in the diestrus phase, there was significantly greater pathology than during estrus phase. The aim of this study was to evaluate transcriptional profiles of infected uterine tissue from mice in either estrus or diestrus phase in order to elucidate possible mechanisms for these differences.

RESULTS: Genes and biological pathways with phase-independent induction during infection showed a chemokine dominant cytokine response to Neisseria gonorrhoeae. Despite general induction being phase-independent, this common anti-gonococcal response demonstrated greater induction during diestrus phase infection. Greater activity of granulocyte adhesion and diapedesis regulators during diestrus infection, particularly in chemokines and diapedesis regulators, was also shown. In addition to a greater induction of the common anti-gonococcal response, Gene Set Enrichment Analysis identified a diestrus-specific induction of type-1 interferon signaling pathways.

CONCLUSIONS: This transcriptional analysis of murine uterine gonococcal infection during distinct points in the natural reproductive cycle provided evidence for a common anti-gonococcal response characterized by significant induction of granulocyte chemokine expression and high proinflammatory mediators. The basic biology of this host response to N. gonorrhoeae in estrus and diestrus is similar at the pathway level but varies drastically in magnitude. Overlaying this, we observed type-1 interferon induction specifically in diestrus infection where greater pathology is observed. This supports recent work suggesting this pathway has a significant, possibly host-detrimental, function in gonococcal infection. Together these findings lay the groundwork for further examination of the role of interferons in gonococcal infection. Additionally, this work enables the implementation of the diestrus uterine infection model using the newly characterized host response as a marker of pathology and its prevention as a correlate of candidate vaccine efficacy and ability to protect against the devastating consequences of N. gonorrhoeae-associated sequelae.}, } @article {pmid30134831, year = {2018}, author = {Antczak, M and Zok, T and Osowiecki, M and Popenda, M and Adamiak, RW and Szachniuk, M}, title = {RNAfitme: a webserver for modeling nucleobase and nucleoside residue conformation in fixed-backbone RNA structures.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {304}, pmid = {30134831}, issn = {1471-2105}, support = {2016/23/B/ST6/03931//The National Science Centre (PL)/ ; }, mesh = {Algorithms ; Base Sequence ; Glutamine/chemistry ; *Internet ; Models, Molecular ; *Nucleic Acid Conformation ; Nucleosides/*genetics ; Nucleotide Motifs ; RNA/*chemistry/*genetics ; RNA, Transfer/chemistry/genetics ; Sequence Analysis, RNA ; *Software ; }, abstract = {BACKGROUND: Computational RNA 3D structure prediction and modeling are rising as complementary approaches to high-resolution experimental techniques for structure determination. They often apply to substitute or complement them. Recently, researchers' interests have directed towards in silico methods to fit, remodel and refine RNA tertiary structure models. Their power lies in a problem-specific exploration of RNA conformational space and efficient optimization procedures. The aim is to improve the accuracy of models obtained either computationally or experimentally.

RESULTS: Here, we present RNAfitme, a versatile webserver tool for remodeling of nucleobase- and nucleoside residue conformations in the fixed-backbone RNA 3D structures. Our approach makes use of dedicated libraries that define RNA conformational space. They have been built upon torsional angle characteristics of PDB-deposited RNA structures. RNAfitme can be applied to reconstruct full-atom model of RNA from its backbone; remodel user-selected nucleobase/nucleoside residues in a given RNA structure; predict RNA 3D structure based on the sequence and the template of a homologous molecule of the same size; refine RNA 3D model by reducing steric clashes indicated during structure quality assessment. RNAfitme is a publicly available tool with an intuitive interface. It is freely accessible at http://rnafitme.cs.put.poznan.pl/ CONCLUSIONS: RNAfitme has been applied in various RNA 3D remodeling scenarios for several types of input data. Computational experiments proved its efficiency, accuracy, and usefulness in the processing of RNAs of any size. Fidelity of RNAfitme predictions has been thoroughly tested for RNA 3D structures determined experimentally and modeled in silico.}, } @article {pmid30134830, year = {2018}, author = {Cong, W and Xing, J and Feng, Y and Wang, J and Fu, R and Yue, B and He, Z and Lin, L and Yang, W and Cheng, J and Sun, W and Cui, S}, title = {The microbiota in the intestinal and respiratory tracts of naked mole-rats revealed by high-throughput sequencing.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {89}, pmid = {30134830}, issn = {1471-2180}, abstract = {BACKGROUND: The naked mole-rat (NMR, Heterocephalus glaber) is being bred as a novel laboratory animal due to its unique biological characteristics, including longevity, cancer resistance, hypoxia tolerance, and pain insensitivity. It is expected that differences exist between the microbiota of wild NMRs and that of NMRs in an artificial environment. Overall, the effect of environment on changes in the NMR microbiota remains unknown. In an attempt to understand the microbiota composition of NMRs in captivity, variability in the microbiota of the intestinal and respiratory tracts of two groups of NMRs was assessed under two conditions.

RESULTS: The results obtained by high-throughput sequencing revealed significant differences at the phylum, class, order, family and genus levels in the microbiota between the two groups of NMRs examined (first group in conventional environment, second group in barrier environment). For the trachea, 24 phyla and 533 genera and 26 phyla and 733 genera were identified for the first and second groups of animals. Regarding the cecum, 23 phyla and 385 genera and 25 phyla and 110 genera were identified in the microbiota of first and second groups of animals. There were no obvious differences between females and males or young and adult animals.

CONCLUSIONS: Our results suggest that the intestinal and respiratory tract NMR microbiota changed during captivity, which may be related to the transition to the breeding environment. Such changes in the microbiota of NMRs may have an effect on the original characteristics, which may be the direction of further research studies.}, } @article {pmid30134828, year = {2018}, author = {Kaliontzopoulou, A and Pinho, C and Martínez-Freiría, F}, title = {Where does diversity come from? Linking geographical patterns of morphological, genetic, and environmental variation in wall lizards.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {124}, pmid = {30134828}, issn = {1471-2148}, support = {IF/00641/2014/CP1256/CT0008//Fundação para a Ciência e a Tecnologia/International ; IF/01597/2014/CP1256/CT0009//Fundação para a Ciência e a Tecnologia/International ; SFRH/BPD/109119/2015//Fundação para a Ciência e a Tecnologia/International ; }, mesh = {Animals ; *Biodiversity ; Biological Evolution ; Genetic Variation ; *Geography ; Lizards/*anatomy & histology/*genetics ; Models, Biological ; Multivariate Analysis ; Phenotype ; Species Specificity ; }, abstract = {BACKGROUND: Understanding how phenotypic variation scales from individuals, through populations, up to species, and how it relates to genetic and environmental factors, is essential for deciphering the evolutionary mechanisms that drive biodiversity. We used two species of Podarcis wall lizards to test whether phenotypic diversity within and divergence across populations follow concordant patterns, and to examine how phenotypic variation responds to genetic and environmental variability across different hierarchical levels of biological organization, in an explicit geographic framework.

RESULTS: We found a general concordance of phenotypic variation across hierarchical levels (i.e. individuals and populations). However, we also found that within-population diversity does not exhibit a coherent geographic structure for most traits, while among-population divergence does, suggesting that different mechanisms may underlie the generation of diversity at these two levels. Furthermore, the association of phenotypic variation with genetic and environmental factors varied extensively between hierarchical levels and across traits, hampering the identification of simple rules to explain what yields diversity.

CONCLUSIONS: Our results in some cases comply with general ecological and evolutionary predictions, but in others they are difficult to explain in the geographic framework used, suggesting that habitat characteristics and other regulatory mechanisms may have a more substantial contribution in shaping phenotypic diversity.}, } @article {pmid30134827, year = {2018}, author = {Azzouz-Olden, F and Hunt, A and DeGrandi-Hoffman, G}, title = {Transcriptional response of honey bee (Apis mellifera) to differential nutritional status and Nosema infection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {628}, pmid = {30134827}, issn = {1471-2164}, support = {EPS-0814194//National Science Foundation/ ; }, mesh = {Animal Nutritional Physiological Phenomena/*genetics ; Animals ; Bees/*genetics/*microbiology/physiology ; Diet ; Host-Pathogen Interactions/genetics ; Microsporidiosis/*genetics/physiopathology ; *Nosema/isolation & purification/pathogenicity ; Pollen ; Transcriptome/*physiology ; }, abstract = {BACKGROUND: Bees are confronting several environmental challenges, including the intermingled effects of malnutrition and disease. Intuitively, pollen is the healthiest nutritional choice, however, commercial substitutes, such as Bee-Pro and MegaBee, are widely used. Herein we examined how feeding natural and artificial diets shapes transcription in the abdomen of the honey bee, and how transcription shifts in combination with Nosema parasitism.

RESULTS: Gene ontology enrichment revealed that, compared with poor diet (carbohydrates [C]), bees fed pollen (P > C), Bee-Pro (B > C), and MegaBee (M > C) showed a broad upregulation of metabolic processes, especially lipids; however, pollen feeding promoted more functions, and superior proteolysis. The superiority of the pollen diet was also evident through the remarkable overexpression of vitellogenin in bees fed pollen instead of MegaBee or Bee-Pro. Upregulation of bioprocesses under carbohydrates feeding compared to pollen (C > P) provided a clear poor nutritional status, uncovering stark expression changes that were slight or absent relatively to Bee-Pro (C > B) or MegaBee (C > M). Poor diet feeding (C > P) induced starvation response genes and hippo signaling pathway, while it repressed growth through different mechanisms. Carbohydrate feeding (C > P) also elicited 'adult behavior', and developmental processes suggesting transition to foraging. Finally, it altered the 'circadian rhythm', reflecting the role of this mechanism in the adaptation to nutritional stress in mammals. Nosema-infected bees fed pollen compared to carbohydrates (PN > CN) upheld certain bioprocesses of uninfected bees (P > C). Poor nutritional status was more apparent against pollen (CN > PN) than Bee-Pro (CN > BN) or MegaBee (CN > MN). Nosema accentuated the effects of malnutrition since more starvation-response genes and stress response mechanisms were upregulated in CN > PN compared to C > P. The bioprocess 'Macromolecular complex assembly' was also enriched in CN > PN, and involved genes associated with human HIV and/or influenza, thus providing potential candidates for bee-Nosema interactions. Finally, the enzyme Duox emerged as essential for guts defense in bees, similarly to Drosophila.

CONCLUSIONS: These results provide evidence of the superior nutritional status of bees fed pollen instead of artificial substitutes in terms of overall health, even in the presence of a pathogen.}, } @article {pmid30134824, year = {2018}, author = {Wang, R and Liu, G and Wang, C and Su, L and Sun, L}, title = {Predicting overlapping protein complexes based on core-attachment and a local modularity structure.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {305}, pmid = {30134824}, issn = {1471-2105}, support = {61772226//National Nature Science Foundation of China/ ; 61373051//National Nature Science Foundation of China/ ; 20140204004GX//Science and Technology Development Program of Jilin Province/ ; }, mesh = {*Algorithms ; Cluster Analysis ; Databases, Protein ; Protein Interaction Mapping/*methods ; Protein Interaction Maps ; Proteins/chemistry ; }, abstract = {BACKGROUND: In recent decades, detecting protein complexes (PCs) from protein-protein interaction networks (PPINs) has been an active area of research. There are a large number of excellent graph clustering methods that work very well for identifying PCs. However, most of existing methods usually overlook the inherent core-attachment organization of PCs. Therefore, these methods have three major limitations we should concern. Firstly, many methods have ignored the importance of selecting seed, especially without considering the impact of overlapping nodes as seed nodes. Thus, there may be false predictions. Secondly, PCs are generally supposed to be dense subgraphs. However, the subgraphs with high local modularity structure usually correspond to PCs. Thirdly, a number of available methods lack handling noise mechanism, and miss some peripheral proteins. In summary, all these challenging issues are very important for predicting more biological overlapping PCs.

RESULTS: In this paper, to overcome these weaknesses, we propose a clustering method by core-attachment and local modularity structure, named CALM, to detect overlapping PCs from weighted PPINs with noises. Firstly, we identify overlapping nodes and seed nodes. Secondly, for a node, we calculate the support function between a node and a cluster. In CALM, a cluster which initially consists of only a seed node, is extended by adding its direct neighboring nodes recursively according to the support function, until this cluster forms a locally optimal modularity subgraph. Thirdly, we repeat this process for the remaining seed nodes. Finally, merging and removing procedures are carried out to obtain final predicted clusters. The experimental results show that CALM outperforms other classical methods, and achieves ideal overall performance. Furthermore, CALM can match more complexes with a higher accuracy and provide a better one-to-one mapping with reference complexes in all test datasets. Additionally, CALM is robust against the high rate of noise PPIN.

CONCLUSIONS: By considering core-attachment and local modularity structure, CALM could detect PCs much more effectively than some representative methods. In short, CALM could potentially identify previous undiscovered overlapping PCs with various density and high modularity.}, } @article {pmid30134123, year = {2019}, author = {Taylor, GT}, title = {Windows into Microbial Seascapes: Advances in Nanoscale Imaging and Application to Marine Sciences.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {465-490}, doi = {10.1146/annurev-marine-121916-063612}, pmid = {30134123}, issn = {1941-0611}, abstract = {Geochemical cycles of all nonconservative elements are mediated by microorganisms over nanometer spatial scales. The pelagic seascape is known to possess microstructure imposed by heterogeneous distributions of particles, polymeric gels, biologically important chemicals, and microbes. While indispensable, most traditional oceanographic observational approaches overlook this heterogeneity and ignore subtleties, such as activity hot spots, symbioses, niche partitioning, and intrapopulation phenotypic variations, that can provide a deeper mechanistic understanding of planktonic ecosystem function. As part of the movement toward cultivation-independent tools in microbial oceanography, techniques to examine the ecophysiology of individual populations and their role in chemical transformations at spatial scales relevant to microorganisms have been developed. This review presents technologies that enable geochemical and microbiological interrogations at spatial scales ranging from 0.02 to a few hundred micrometers, particularly focusing on atomic force microscopy, nanoscale secondary ion mass spectrometry, and confocal Raman microspectroscopy and introducing promising approaches for future applications in marine sciences.}, } @article {pmid30134119, year = {2018}, author = {Pierre-Jerome, E and Drapek, C and Benfey, PN}, title = {Regulation of Division and Differentiation of Plant Stem Cells.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {289-310}, doi = {10.1146/annurev-cellbio-100617-062459}, pmid = {30134119}, issn = {1530-8995}, abstract = {A major challenge in developmental biology is unraveling the precise regulation of plant stem cell maintenance and the transition to a fully differentiated cell. In this review, we highlight major themes coordinating the acquisition of cell identity and subsequent differentiation in plants. Plant cells are immobile and establish position-dependent cell lineages that rely heavily on external cues. Central players are the hormones auxin and cytokinin, which balance cell division and differentiation during organogenesis. Transcription factors and miRNAs, many of which are mobile in plants, establish gene regulatory networks that communicate cell position and fate. Small peptide signaling also provides positional cues as new cell types emerge from stem cell division and progress through differentiation. These pathways recruit similar players for patterning different organs, emphasizing the modular nature of gene regulatory networks. Finally, we speculate on the outstanding questions in the field and discuss how they may be addressed by emerging technologies.}, } @article {pmid30133703, year = {2018}, author = {Taylor, JN and Ternes, WM and Lattanzio, MS}, title = {Natural selection favors local specialization in a widespread habitat generalist.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2090-2099}, doi = {10.1111/evo.13584}, pmid = {30133703}, issn = {1558-5646}, support = {2016 Youth Activity Fund//Explorers Club/ ; Faculty Development Grant//Christopher Newport University/ ; Honor's Summer Research Stipend (x2)//Christopher Newport University/ ; }, abstract = {The ecological success of widespread species is attributed to an ability to generalize across diverse habitats, a so-called "jack of all trades" scenario. However, this assumption ignores the potential for local specialization, an alternative scenario whereby spatial variation in natural selection generates habitat-specific fitness surfaces. Despite a growing recognition of spatial variation in selection in nature, and the inevitable exploitation of distinct habitat types across an extensive geographic range, attention to this hypothesis has been lacking for widespread taxa. We test this hypothesis using data from four populations of a widespread species drawing from two distinct habitat types (tree- and boulder-dominated, respectively). Specifically, we compare major physiological traits of male and female lizards by habitat type and then estimate the shape of natural selection gradients on those traits for each sex in each habitat (i.e., their fitness surfaces). We detected significant differences in morphology and performance across habitats that mirror interspecific patterns. Importantly, patterns of linear and nonlinear selection on these traits were habitat-specific for both sexes, supporting a clear but underappreciated capacity for local specialization. Our findings challenge assumptions of habitat generalism in widespread taxa, and instead provide some evidence for adaptive diversification in driving their ecological success.}, } @article {pmid30133698, year = {2018}, author = {Stamps, JA and Biro, PA and Mitchell, DJ and Saltz, JB}, title = {Bayesian updating during development predicts genotypic differences in plasticity.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2167-2180}, doi = {10.1111/evo.13585}, pmid = {30133698}, issn = {1558-5646}, support = {National Institutes of Health grant #MH091561//Sergey V. Nuzhdin/ ; }, abstract = {Interactions between genotypes and environments are central to evolutionary genetics, but such interactions are typically described, rather than predicted from theory. Recent Bayesian models of development generate specific predictions about genotypic differences in developmental plasticity (changes in the value of a given trait as a result of a given experience) based on genotypic differences in the value of the trait that is expressed by naïve subjects. We used these models to make a priori predictions about the effects of an aversive olfactory conditioning regime on the response of Drosophila melanogaster larvae to the odor of ethyl acetate. As predicted, across 116 genotypes initial trait values were related to plasticity. Genotypes most strongly attracted to the odor of ethyl acetate when naïve reduced their attraction scores more as a result of the aversive training regime than those less attracted to the same odor when naïve. Thus, as predicted, the variance across genotypes in attraction scores was higher before than after the shared experience. These results support predictions generated by Bayesian models of development and indicate that such models can be successfully used to investigate how variation across genotypes in information derived from ancestors combines with personal experience to differentially affect developmental plasticity in response to specific types of experience.}, } @article {pmid30133077, year = {2018}, author = {Zichello, JM}, title = {Look in the trees: Hylobatids as evolutionary models for extinct hominins.}, journal = {Evolutionary anthropology}, volume = {27}, number = {4}, pages = {142-146}, doi = {10.1002/evan.21715}, pmid = {30133077}, issn = {1520-6505}, mesh = {Animals ; Anthropology, Physical ; *Biological Evolution ; Body Size/physiology ; Ecology ; Extinction, Biological ; Female ; Fossils ; Hominidae ; *Hylobatidae/classification/physiology ; Male ; Phylogeny ; }, abstract = {Studying extant apes is of central importance to paleoanthropology. This approach is informative in inferring how hominin skeletal morphology reflects phylogeny, behavior, development, and ecological context. Traditionally, great apes have dominated the paleoanthropological literature as extant analogs for extinct hominins, to the exclusion of their phylogenetic sister group, the hylobatids. Phylogenetic proximity, large body size, and high encephalization quotients may have contributed to decisions to use great apes as models for hominins. However, if we reexamine hylobatids as extant models for extinct hominins-using modern phylogenetic, behavioral, and ecological data-this clade is uniquely poised to inform future frameworks in paleoanthropology. The following features make hylobatids strong analogs for extinct hominins: taxonomic diversity, the timing of diversification, hybridization between species, small body size, and reduced sexual dimorphism. Based on these shared features, hylobatids offer future opportunities to paleoanthropology, and provide a much richer extant analog than is currently recognized.}, } @article {pmid30132753, year = {2018}, author = {Liu, LX and Liu, SX and Wang, YM and Bi, JC and Chen, HM and Deng, J and Zhang, C and Hu, QS and Li, CF}, title = {Komagataeibacter cocois sp. nov., a novel cellulose-producing strain isolated from coconut milk.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3125-3131}, doi = {10.1099/ijsem.0.002947}, pmid = {30132753}, issn = {1466-5034}, mesh = {Acetobacteraceae/*classification/genetics/isolation & purification ; Animals ; Bacterial Typing Techniques ; Base Composition ; China ; Cocos/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fermented Foods/*microbiology ; *Food Microbiology ; Genes, Bacterial ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Phylogenetic analysis was performed on a cellulose-producing strain, designated WE7T, isolated from contaminated coconut milk. The analysis utilized nearly complete 16S rRNA gene sequences, as well as concatenated partial sequences of the housekeeping genes dnaK, groEL and rpoB, and allowed identification of the strain as belonging to the genus Komagataeibacter. DNA-DNA correlation or average nucleotide identity analysis was performed between WE7T and its closest phylogenetic neighbours, and the resulting values were below the species level (<70 % and <95 %), suggesting that the strain represents a novel species in genus Komagataeibacter. Strain WE7T was coupled with Komagataeibacter species more tightly than with Gluconacetobacter species in a 16S rRNA gene sequence phylogenetic tree. Strain WE7T can be differentiated from closely related Komagataeibacter and Gluconacetobacter entanii species by the ability to grow on the carbon sources d-mannitol, sodium d-gluconate and glycerol, the ability to form acid by d-fructose, sucrose, d-mannitol, d-galactose and ethanol, and the ability to grow without acetic acid. The major fatty acid of WE7T is C18 : 1ω9c (52.3 %). The DNA G+C content of WE7T is 63.2 mol%. The name Komagataeibacter cocois sp. nov. is proposed, with the type strain WE7T (=CGMCC 1.15338T=JCM 31140T).}, } @article {pmid30132752, year = {2018}, author = {Ambika Manirajan, B and Suarez, C and Ratering, S and Rusch, V and Geissler-Plaum, R and Cardinale, M and Schnell, S}, title = {Spirosoma pollinicola sp. nov., isolated from pollen of common hazel (Corylus avellana L.).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3248-3254}, doi = {10.1099/ijsem.0.002973}, pmid = {30132752}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Base Sequence ; Corylus/*microbiology ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Germany ; Phosphatidylethanolamines/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pollen/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-negative bacterium, strain HA7T, was isolated from the microhabitat of common hazel (Corylus avellana L.) pollen. HA7T was found to be an aerobic, rod-shaped, catalase-positive, oxidase-negative bacterium with an optimum growth temperature of 25 °C and pH of 7. The nearly complete 16S rRNA gene sequence of HA7T strain showed the closest similarities to Spirosoma linguale DSM 74T (97.4 %) and Spirosoma fluviale DSM 29961T (97.43 %). The major fatty acids (>5 %) were C16 : 1ω5c, summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), iso-C15 : 0 and iso-C17 : 0 3-OH. The major polar lipids were an unidentified aminophospholipid and phosphatidylethanolamine. The major respiratory quinone detected was menaquinone MK-7 (95 %). The draft genome sequence included 8 794 837 bases, which contained 3665 predicted coding sequences and had a G+C content of 47.9 mol%. The genome-based comparison between HA7T and S. linguale DSM 74T and S. fluviale DSM 29961T with pairwise average nucleotide identity indicated a clear distinction, between 76.2-76.3 %. Moreover, the digital DNA-DNA relatedness of HA7T to these strains was 26.5 and 25.1 %. Based on the differential genotypic, phenotypic and chemotaxonomic properties to closely related type strains, strain HA7T ought to be assigned with the status of a new species, for which the name Spirosomapollinicola sp. nov. is proposed. The type strain is HA7T (DSM 105799T=LMG 30282T).}, } @article {pmid30131542, year = {2018}, author = {}, title = {Referees should exercise their rights.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {409}, doi = {10.1038/d41586-018-06006-y}, pmid = {30131542}, issn = {1476-4687}, } @article {pmid30131541, year = {2018}, author = {Schubert, C}, title = {How working as a research technician can bolster your scientific career.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {517-519}, doi = {10.1038/d41586-018-05991-4}, pmid = {30131541}, issn = {1476-4687}, } @article {pmid30131539, year = {2018}, author = {Else, H}, title = {Top geneticist loses £3.5-million grant in first test of landmark bullying policy.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {420}, doi = {10.1038/d41586-018-06009-9}, pmid = {30131539}, issn = {1476-4687}, } @article {pmid30131538, year = {2018}, author = {Witze, A}, title = {World's first wind-mapping satellite set to launch.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {420-421}, doi = {10.1038/d41586-018-05976-3}, pmid = {30131538}, issn = {1476-4687}, } @article {pmid30131537, year = {2018}, author = {}, title = {The serious disease that awaits some ex-smokers.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {413}, doi = {10.1038/d41586-018-05958-5}, pmid = {30131537}, issn = {1476-4687}, } @article {pmid30131536, year = {2018}, author = {}, title = {A compound offers itch and pain relief without side effects.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {412}, doi = {10.1038/d41586-018-05957-6}, pmid = {30131536}, issn = {1476-4687}, } @article {pmid30131535, year = {2018}, author = {}, title = {A sensor detects the light touch of a single molecule.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {413}, doi = {10.1038/d41586-018-05950-z}, pmid = {30131535}, issn = {1476-4687}, } @article {pmid30131534, year = {2018}, author = {}, title = {Teens stumble on a new class of astronomical object.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {413}, doi = {10.1038/d41586-018-05959-4}, pmid = {30131534}, issn = {1476-4687}, } @article {pmid30131533, year = {2018}, author = {Masood, E}, title = {What Pakistan's new government means for science.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {419}, doi = {10.1038/d41586-018-05974-5}, pmid = {30131533}, issn = {1476-4687}, } @article {pmid30131532, year = {2018}, author = {}, title = {Americans farmed a huge and raucous parrot a millennium ago.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {412}, doi = {10.1038/d41586-018-05932-1}, pmid = {30131532}, issn = {1476-4687}, } @article {pmid30131531, year = {2018}, author = {}, title = {Live bacteria deliver crucial enzymes straight to the gut.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {412}, doi = {10.1038/d41586-018-05949-6}, pmid = {30131531}, issn = {1476-4687}, } @article {pmid30131530, year = {2018}, author = {}, title = {Matchmaking clues for clever crows that are close to extinction.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {413}, doi = {10.1038/d41586-018-05901-8}, pmid = {30131530}, issn = {1476-4687}, } @article {pmid30131524, year = {2018}, author = {Munk, P and Knudsen, BE and Lukjancenko, O and Duarte, ASR and Van Gompel, L and Luiken, REC and Smit, LAM and Schmitt, H and Garcia, AD and Hansen, RB and Petersen, TN and Bossers, A and Ruppé, E and Lund, O and Hald, T and Pamp, SJ and Vigre, H and Heederik, D and Wagenaar, JA and Mevius, D and Aarestrup, FM and , }, title = {Author Correction: Abundance and diversity of the faecal resistome in slaughter pigs and broilers in nine European countries.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1186}, doi = {10.1038/s41564-018-0241-4}, pmid = {30131524}, issn = {2058-5276}, abstract = {In the version of this Article originally published, the surname of author Oksana Lukjancenko was spelt incorrectly as 'Lukjacenko'. This has now been corrected.}, } @article {pmid30131433, year = {2018}, author = {Li, Z and Yu, S and Wang, L and Mehmood, K and Liu, W and Alapaty, K}, title = {Suppression of convective precipitation by elevated man-made aerosols is responsible for large-scale droughts in north China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8327-E8328}, pmid = {30131433}, issn = {1091-6490}, } @article {pmid30131432, year = {2018}, author = {Day, JA and Fung, IY and Liu, W}, title = {Reply to Li et al: Late 20th-century drought in northern China reflects influence of global warming, aerosols, and natural variability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8329}, pmid = {30131432}, issn = {1091-6490}, } @article {pmid30131431, year = {2018}, author = {Blake, KR and Bastian, B and Denson, TF and Grosjean, P and Brooks, RC}, title = {Income inequality not gender inequality positively covaries with female sexualization on social media.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8722-8727}, pmid = {30131431}, issn = {1091-6490}, mesh = {Female ; Humans ; *Income ; *Interpersonal Relations ; *Social Media ; *Socioeconomic Factors ; United States ; }, abstract = {Publicly displayed, sexualized depictions of women have proliferated, enabled by new communication technologies, including the internet and mobile devices. These depictions are often claimed to be outcomes of a culture of gender inequality and female oppression, but, paradoxically, recent rises in sexualization are most notable in societies that have made strong progress toward gender parity. Few empirical tests of the relation between gender inequality and sexualization exist, and there are even fewer tests of alternative hypotheses. We examined aggregate patterns in 68,562 sexualized self-portrait photographs ("sexy selfies") shared publicly on Twitter and Instagram and their association with city-, county-, and cross-national indicators of gender inequality. We then investigated the association between sexy-selfie prevalence and income inequality, positing that sexualization-a marker of high female competition-is greater in environments in which incomes are unequal and people are preoccupied with relative social standing. Among 5,567 US cities and 1,622 US counties, areas with relatively more sexy selfies were more economically unequal but not more gender oppressive. A complementary pattern emerged cross-nationally (113 nations): Income inequality positively covaried with sexy-selfie prevalence, particularly within more developed nations. To externally validate our findings, we investigated and confirmed that economically unequal (but not gender-oppressive) areas in the United States also had greater aggregate sales in goods and services related to female physical appearance enhancement (beauty salons and women's clothing). Here, we provide an empirical understanding of what female sexualization reflects in societies and why it proliferates.}, } @article {pmid30131430, year = {2018}, author = {Borgerhoff Mulder, M}, title = {Economic inequality drives female sexualization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8658-8660}, pmid = {30131430}, issn = {1091-6490}, mesh = {Female ; Humans ; *Socioeconomic Factors ; }, } @article {pmid30131429, year = {2018}, author = {Telkes, I and Viswanathan, A and Jimenez-Shahed, J and Abosch, A and Ozturk, M and Gupte, A and Jankovic, J and Ince, NF}, title = {Local field potentials of subthalamic nucleus contain electrophysiological footprints of motor subtypes of Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8567-E8576}, pmid = {30131429}, issn = {1091-6490}, mesh = {Aged ; Aged, 80 and over ; *Beta Rhythm ; Female ; Humans ; Male ; Middle Aged ; Parkinson Disease/*classification/*physiopathology ; Subthalamic Nucleus/*physiopathology ; }, abstract = {Although motor subtypes of Parkinson's disease (PD), such as tremor dominant (TD) and postural instability and gait difficulty (PIGD), have been defined based on symptoms since the mid-1990s, no underlying neural correlates of these clinical subtypes have yet been identified. Very limited data exist regarding the electrophysiological abnormalities within the subthalamic nucleus (STN) that likely accompany the symptom severity or the phenotype of PD. Here, we show that activity in subbands of local field potentials (LFPs) recorded with multiple microelectrodes from subterritories of STN provide distinguishing neurophysiological information about the motor subtypes of PD. We studied 24 patients with PD and found distinct patterns between TD (n = 13) and PIGD (n = 11) groups in high-frequency oscillations (HFOs) and their nonlinear interactions with beta band in the superior and inferior regions of the STN. Particularly, in the superior region of STN, the power of the slow HFO (sHFO) (200-260 Hz) and the coupling of its amplitude with beta-band phase were significantly stronger in the TD group. The inferior region of STN exhibited fast HFOs (fHFOs) (260-450 Hz), which have a significantly higher center frequency in the PIGD group. The cross-frequency coupling between fHFOs and beta band in the inferior region of STN was significantly stronger in the PIGD group. Our results indicate that the spatiospectral dynamics of STN-LFPs can be used as an objective method to distinguish these two motor subtypes of PD. These observations might lead to the development of sensing and stimulation strategies targeting the subterritories of STN for the personalization of deep-brain stimulation (DBS).}, } @article {pmid30131428, year = {2018}, author = {Piot, M and Abécassis, B and Brouri, D and Troufflard, C and Proust, A and Izzet, G}, title = {Control of the hierarchical self-assembly of polyoxometalate-based metallomacrocycles by redox trigger and solvent composition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8895-8900}, pmid = {30131428}, issn = {1091-6490}, abstract = {Discrete metallomacrocycles are attractive scaffolds for the formation of complex supramolecular architectures with emergent properties. We herein describe the formation of hierarchical nanostructures using preformed metallomacrocycles by coordination-driven self-assembly of a covalent organic-inorganic polyoxometalate (POM)-based hybrid. In this system, we take advantage of the presence of charged subunits (POM, metal linker, and counterions) within the metallomacrocycles, which drive their aggregation through intermolecular electrostatic interactions. We show that the solvent composition and the charge of the metal linker are key parameters that steer the supramolecular organization. Different types of hierarchical self-assemblies, zero-dimensional (0D) dense nanoparticles, and 1D worm-like nanoobjects, can be selectively formed owing to different aggregation modes of the metallomacrocycles. Finally, we report that the worm-like structures drastically enhance the solubility in water of a pyrene derivative and can act as molecular carriers.}, } @article {pmid30131427, year = {2018}, author = {Sun, C and Shen, M and Chavez, AD and Evans, AM and Liu, X and Harutyunyan, B and Flanders, NC and Hersam, MC and Bedzyk, MJ and Olvera de la Cruz, M and Dichtel, WR}, title = {High aspect ratio nanotubes assembled from macrocyclic iminium salts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8883-8888}, pmid = {30131427}, issn = {1091-6490}, abstract = {One-dimensional nanostructures such as carbon nanotubes and actin filaments rely on strong and directional interactions to stabilize their high aspect ratio shapes. This requirement has precluded making isolated, long, thin organic nanotubes by stacking molecular macrocycles, as their noncovalent stacking interactions are generally too weak. Here we report high aspect ratio (>103), lyotropic nanotubes of stacked, macrocyclic, iminium salts, which are formed by protonation of the corresponding imine-linked macrocycles. Iminium ion formation establishes cohesive interactions that, in organic solvent (tetrahydrofuran), are two orders of magnitude stronger than the neutral macrocycles, as explained by physical arguments and demonstrated by molecular dynamics simulations. Nanotube formation stabilizes the iminium ions, which otherwise rapidly hydrolyze, and is reversed and restored upon addition of bases and acids. Acids generated by irradiating a photoacid generator or sonicating chlorinated solvents also induced nanotube assembly, allowing these nanostructures to be coupled to diverse stimuli, and, once assembled, they can be fixed permanently by cross-linking their pendant alkenes. As large macrocyclic chromonic liquid crystals, these iminium salts are easily accessible through a modular design and provide a means to rationally synthesize structures that mimic the morphology and rheology of carbon nanotubes and biological tubules.}, } @article {pmid30131210, year = {2018}, author = {Duthie, MS and Lison, A and Courtenay, O}, title = {Advances toward Diagnostic Tools for Managing Zoonotic Visceral Leishmaniasis.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {881-890}, pmid = {30131210}, issn = {1471-5007}, support = {//Wellcome Trust/United Kingdom ; R01 AI025038/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Dog Diseases/diagnosis/prevention & control/transmission ; Dogs ; Humans ; Leishmania infantum/physiology ; Leishmaniasis, Visceral/*diagnosis/*prevention & control/transmission ; Psychodidae/parasitology ; Zoonoses/*diagnosis/*prevention & control/transmission ; }, abstract = {Visceral leishmaniasis (VL) is a life-threatening outcome of Leishmania infantum or Leishmania donovani infection. Dogs are the primary domestic reservoir of L. infantum parasites, and ownership of infected dogs increases the risk of human VL. Controlling infection within dog populations is regarded as critical to VL management in endemic countries, both preventing progression of canine disease and limiting parasite transmission to humans and dogs. Here we discuss various strategies that are used to diagnose canine visceral leishmaniasis (CVL) and the possibilities of adapting these for use within population screening and control programs. In addition, given the variable transmissibility of L. infantum to the sand fly vector, we outline some possibilities for the preferential identification of 'super-spreader' dogs among the overall infected population.}, } @article {pmid30131185, year = {2018}, author = {Leist, SR and Baric, RS}, title = {Giving the Genes a Shuffle: Using Natural Variation to Understand Host Genetic Contributions to Viral Infections.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {10}, pages = {777-789}, doi = {10.1016/j.tig.2018.07.005}, pmid = {30131185}, issn = {0168-9525}, abstract = {The laboratory mouse has proved an invaluable model to identify host factors that regulate the progression and outcome of virus-induced disease. The paradigm is to use single-gene knockouts in inbred mouse strains or genetic mapping studies using biparental mouse populations. However, genetic variation among these mouse strains is limited compared with the diversity seen in human populations. To address this disconnect, a multiparental mouse population has been developed to specifically dissect the multigenetic regulation of complex disease traits. The Collaborative Cross (CC) population of recombinant inbred mouse strains is a well-suited systems-genetics tool to identify susceptibility alleles that control viral and microbial infection outcomes and immune responses and to test the promise of personalized medicine.}, } @article {pmid30131068, year = {2018}, author = {Jiao, S and Chen, W and Wang, J and Du, N and Li, Q and Wei, G}, title = {Soil microbiomes with distinct assemblies through vertical soil profiles drive the cycling of multiple nutrients in reforested ecosystems.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {146}, pmid = {30131068}, issn = {2049-2618}, mesh = {Archaea/*classification/genetics/isolation & purification/metabolism ; Bacteria/*classification/genetics/isolation & purification/metabolism ; Biodiversity ; Fungi/*classification/genetics/isolation & purification/metabolism ; Metagenomics ; Nutrients/metabolism ; Phylogeny ; Plant Roots/microbiology ; Sequence Analysis, DNA ; Soil/chemistry ; Soil Microbiology ; Trees/*growth & development/microbiology ; }, abstract = {BACKGROUND: Soil microbiomes play an important role in the services and functioning of terrestrial ecosystems. However, little is known of their vertical responses to restoration process and their contributions to soil nutrient cycling in the subsurface profiles. Here, we investigated the community assembly of soil bacteria, archaea, and fungi along vertical (i.e., soil depths of 0-300 cm) and horizontal (i.e., distance from trees of 30-90 cm) profiles in a chronosequence of reforestation sites that represent over 30 years of restoration.

RESULTS: In the superficial layers (0-80 cm), bacterial and fungal diversity decreased, whereas archaeal diversity increased with increasing soil depth. As reforestation proceeded over time, the vertical spatial variation in bacterial communities decreased, while that in archaeal and fungal communities increased. Vertical distributions of the soil microbiomes were more related to the variation in soil properties, while their horizontal distributions may be driven by a gradient effect of roots extending from the tree. Bacterial and archaeal beta-diversity were strongly related to multi-nutrient cycling in the soil, respectively, playing major roles in deep and superficial layers.

CONCLUSIONS: Taken together, these results reveal a new perspective on the vertical and horizontal spatial variation in soil microbiomes at the fine scale of single trees. Distinct response patterns underpinned the contributions of soil bacteria, archaea, and fungi as a function of subsurface nutrient cycling during the reforestation of ex-arable land.}, } @article {pmid30130751, year = {2018}, author = {Garza-Gisholt, E and Hart, NS and Collin, SP}, title = {Retinal Morphology and Visual Specializations in Three Species of Chimaeras, the Deep-Sea R. pacifica and C. lignaria, and the Vertical Migrator C. milii (Holocephali).}, journal = {Brain, behavior and evolution}, volume = {92}, number = {1-2}, pages = {47-62}, doi = {10.1159/000490655}, pmid = {30130751}, issn = {1421-9743}, abstract = {The majority of holocephalans live in the mesopelagic zone of the deep ocean, where there is little or no sunlight, but some species migrate to brightly lit shallow waters to reproduce. This study compares the retinal morphology of two species of deep-sea chimaeras, the Pacific spookfish (Rhinochimaera pacifica) and the Carpenter's chimaera (Chimaera lignaria), with the elephant shark (Callorhinchus milii), a vertical migrator that lives in the mesopelagic zone but migrates to shallow water to reproduce. The two deep-sea chimaera species possess pure rod retinae with long photoreceptor outer segments that might serve to increase visual sensitivity. In contrast, the retina of the elephant shark possesses rods, with an outer-segment length significantly shorter (a mean of 34 µm) than in the deep-sea species, and cones, and therefore the potential for color vision. The retinal ganglion cell distribution closely follows that of the photoreceptor populations in all three species, but there is a lower peak density of these cells in both deep-sea species (215-275 cells/mm2 vs. 769 cells/mm2 in the elephant shark), which represents a significant increase in the convergence of visual information (summation ratio) from photoreceptors to ganglion cells. It is evident that the eyes of deep-sea chimaeras have increased sensitivity to detect objects under low levels of light, but at the expense of both resolution and the capacity for color vision. In contrast, the elephant shark has a lower sensitivity, but the potential for color discrimination and a higher visual acuity.}, } @article {pmid30129921, year = {2018}, author = {Cho, ES and Cha, IT and Roh, SW and Nam, YD and Seo, MJ}, title = {Haloplanus rallus sp. nov., a halophilic archaeon isolated from crude solar salt.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3226-3231}, doi = {10.1099/ijsem.0.002970}, pmid = {30129921}, issn = {1466-5034}, mesh = {Base Composition ; DNA, Archaeal/genetics ; Genes, Archaeal ; Glycolipids/chemistry ; Halobacteriaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Sodium Chloride ; }, abstract = {A halophilic archaeon, strain MBLA0036T, was isolated from Sorae solar saltern near Incheon, Republic of Korea. Strain MBLA0036T had three 16S rRNA genes: rrnA, rrnB and rrnC. The 16S rRNA gene sequence similarities between strain MBLA0036T (based on the rrnA gene) and Haloplanus ruber R35T and Haloplanus litoreus GX21T were 98.0 and 97.3 %, respectively. The similarities of the RNA polymerase subunit B' gene between strain MBLA0036T and H. ruber R35T and H. litoreus GX21T were 94.0 and 92.1 %, respectively. Cells of strain MBLA0036T were Gram-stain-negative, motile, red-pigmented, pleomorphic, flat and contained gas vesicles. Strain MBLA0036T grew at 15‒55 °C (optimum, 37 °C), in 10‒30 % (w/v) NaCl (15 %, w/v) with 0‒0.5 M MgSO4.7H2O (0.2 M) and at pH 6.0-9.0 (pH 7.0). The cells lysed in distilled water and the minimum NaCl concentration that prevented cell lysis was 5 % (w/v). Major polar lipids of strain MBLA0036T were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate and a glycolipid that was chromatographically identical to sulfated mannosyl glucosyl diether. The major isoprenoid quinone was menaquinone-8. The genomic DNA G+C content was 65.5 mol%. DNA-DNA hybridization values between strain MBLA0036T and H. ruber JCM 17271T and H. litoreus JCM 17092T were 35±3 and 18±1 %, respectively. Therefore, strain MBLA0036T is described a novel species of the Haloplanus, for which we propose the name Haloplanusrallus sp. nov. The type strain is MBLA0036T (=KCTC 4239T=JCM 31425T).}, } @article {pmid30129920, year = {2018}, author = {Kim, DU and Kim, JY and Jang, JH and Kim, MK}, title = {Pontibacter terrae sp. nov., isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3184-3189}, doi = {10.1099/ijsem.0.002964}, pmid = {30129920}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A bacterial strain, designated 17SD1-15T, was isolated from soil. Cells of this strain were Gram-stain-negative and aerobic rods. The major fatty acids of strain 17SD1-15T were iso-C15 : 0 and summed feature 4 (anteiso-C17 : 1 B and/or iso-C17 : 1 I). The polar lipids were phosphatidylethanolamine, one phospholipid and five unidentified lipids. The G+C content of the genomic DNA of strain 17SD1-15T was 49.0 mol%. The 16S rRNA gene sequence analysis showed that strain 17SD1-15T was phylogenetically related to Pontibacter saemangeumensis GCM0142T, Pontibacter korlensis X14-1T, Pontibacter yuliensis H9XT, Pontibacter diazotrophicus H4XT and Pontibacter humi SWU8T (98.3, 96.4, 96.4, 96.4 and 96.0 % sequence similarity, respectively). DNA-DNA relatedness between 17SD1-15T and the most closely related type strain of Pontibacter species was 42.9±0.8 %. The low level of DNA-DNA relatedness identified strain 17SD1-15T as a member of a novel species in the genus Pontibacter. The results of genotypic and phenotypic data, including chemotaxonomic traits, showed that strain 17SD1-15T could be distinguished from its phylogenetically related species. Therefore, strain 17SD1-15T represents a novel species within the genus Pontibacter, for which the name Pontibacter terrae sp. nov. is proposed, with the type strain 17SD1-15T (=KCTC 52915T=NBRC 113057T).}, } @article {pmid30129919, year = {2018}, author = {Kaur, N and Seuylemezian, A and Patil, PP and Patil, P and Krishnamurti, S and Varelas, J and Smith, DJ and Mayilraj, S and Vaishampayan, P}, title = {Paenibacillus xerothermodurans sp. nov., an extremely dry heat resistant spore forming bacterium isolated from the soil of Cape Canaveral, Florida.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3190-3196}, doi = {10.1099/ijsem.0.002967}, pmid = {30129919}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Florida ; *Hot Temperature ; Nucleic Acid Hybridization ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Spores, Bacterial ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, motile, endospore-producing, facultative anaerobic bacterial strain, designated ATCC 27380T, was isolated from heat-stressed soil of Cape Canaveral, Florida, USA. Growth was observed at 20-42 °C (optimum, 37 °C), at pH 6.0-10.0 (optimum pH 7.0) and in the presence of 0.5-3 % NaCl (optimum 0.5 %). The cell wall contained meso-diaminopimelic acid as the diagnostic amino acid and the isoprenoid quinone was MK-7. The polar lipids present were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol and one unknown phospholipid. The main fatty acids were iso-C15 : 0 and anteiso-C15 : 0. Phylogenetic analysis based on 16S rRNA gene sequencing affiliated strain ATCC 27380T to the genus Paenibacillus, and showed the highest sequence similarity to Paenibacillus rigui JCM 16352T (97.0 %). The other closely related type strains exhibited 16S rRNA gene sequence similarity values below 95.9 %. The draft genome of ATCC 27380T had a size of 4,361,187 bases, with a G+C content of 51.0 %. The average nucleotide identity and in silico DNA-DNA hybridization values between strain ATCC 27380T and P. rigui JCM 16352T were 72.5% and 18.5 %, respectively, which were below the threshold suggested for species differentiation (96% and 70 %, respectively). The average amino acid identity between strain ATCC 27380T and P. rigui JCM 16352T was 68.72 %, which was above the suggested genus level demarcation of 65 %. Based on phenotypic, genotypic and chemotaxonomic data, strain ATCC 27380T represents a novel species in the genus Paenibacillus, for which the name Paenibacillusxerothermodurans sp. nov. (=DSM 520T=NRRL NRS-1629T=ATCC 27380T) is proposed.}, } @article {pmid30129917, year = {2018}, author = {Chen, WM and Su, CL and Kwon, SW and Sheu, SY}, title = {Flavobacterium effusum sp. nov., isolated from a freshwater river.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3111-3117}, doi = {10.1099/ijsem.0.002944}, pmid = {30129917}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Polyamines/chemistry ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; Taiwan ; Vitamin K 2/chemistry ; }, abstract = {A yellowish-orange-coloured bacterial strain, PSI-22T, was isolated from a freshwater river in Taiwan. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain PSI-22T belonged to the genus Flavobacterium and showed the highest identity with respect to Flavobacterium dispersum MVW-23T (98.0 %), Flavobacterium tistrianum GB 56.1T (97.1 %), Flavobacterium denitrificans ED5T (97.1 %) and Flavobacterium daemonense THG-DJ7T (97.0 %) and less than 97 % to other members of the genus. Cells of strain PSI-22T were Gram-negative, strictly aerobic, motile by gliding and rod-shaped. Optimal growth occurred at 30 °C, pH 6 and in the presence of 0.5 % NaCl. Strain PSI-22T contained iso-C15 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) as the predominant fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, one uncharacterized aminophospholipid, one uncharacterized aminophosphoglycolipid, two uncharacterized aminolipids, one uncharacterized phospholipid and one uncharacterized lipid. The major polyamine was homospermidine. The major isoprenoid quinone was MK-6 and the DNA G+C content of the genomic DNA was 41.4 mol%. The DNA-DNA hybridization value for strain PSI-22T with F. dispersum BCRC 80978T, F. tistrianum KCTC 42679T, F. denitrificans DSM 15936T and F. daemonense KACC 17651T was less than 30 %. On the basis of the phylogenetic inference and phenotypic data, strain PSI-22T should be classified as a novel species, for which the name Flavobacterium effusum sp. nov. is proposed. The type strain is PSI-22T (=BCRC 80973T=LMG 29553T=KCTC 52233T).}, } @article {pmid30129916, year = {2018}, author = {Kim, DU and Jang, JH and Kang, MS and Kim, JY and Zhang, J and Lim, S and Kim, MK}, title = {Deinococcus irradiatisoli sp. nov., isolated from gamma ray-irradiated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3232-3236}, doi = {10.1099/ijsem.0.002968}, pmid = {30129916}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Deinococcus/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; *Gamma Rays ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain 17bor-2T, a gamma-resistant, pink-to-red-coloured, aerobic, catalase-positive, oxidase-negative and Gram-stain-negative bacterium, was isolated from gamma ray-irradiated soil. The isolate grew aerobically at 18-37 °C (optimum, 28-30 °C), pH 6.0-8.0 (pH 6.5-7.5) and in the presence of 0-1 % (w/v) NaCl (0 % NaCl). Phylogenetic analysis based on its 16S rRNA gene sequence indicated that strain 17bor-2T belonged to the genus Deinococcus with a highest sequence similarity of 96.4 % to Deinococcus alpinitundrae ME-04-04-52T. The major fatty acids of the strain were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and cyclo C17 : 0. The only respiratory quinone was MK-8. The major polar lipids of the strain were phosphoglycolipid, aminophospholipid and an unknown glycolipid. The DNA G+C content of strain 17bor-2T was 62.8 mol%. On the basis of its phenotypic, genotypic and chemotaxonomic characteristics, strain 17bor-2T should be classified as a novel species in the genus Deinococcus, for which the name Deinococcusirradiatisoli sp. nov. is proposed. The type strain is 17bor-2T (=KCTC 33907T=NBRC 113037T).}, } @article {pmid30129423, year = {2018}, author = {Woodruff, GC and Phillips, PC}, title = {Field studies reveal a close relative of C. elegans thrives in the fresh figs of Ficus septica and disperses on its Ceratosolen pollinating wasps.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {26}, pmid = {30129423}, issn = {1472-6785}, support = {R01 GM-102511/NH/NIH HHS/United States ; F32 GM115209/GM/NIGMS NIH HHS/United States ; 5F32GM115209-03/NH/NIH HHS/United States ; PE13557//Japan Society for the Promotion of Science/International ; R01 GM102511/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Biotic interactions are ubiquitous and require information from ecology, evolutionary biology, and functional genetics in order to be understood. However, study systems that are amenable to investigations across such disparate fields are rare. Figs and fig wasps are a classic system for ecology and evolutionary biology with poor functional genetics; Caenorhabditis elegans is a classic system for functional genetics with poor ecology. In order to help bridge these disciplines, here we describe the natural history of a close relative of C. elegans, Caenorhabditis inopinata, that is associated with the fig Ficus septica and its pollinating Ceratosolen wasps.

RESULTS: To understand the natural context of fig-associated Caenorhabditis, fresh F. septica figs from four Okinawan islands were sampled, dissected, and observed under microscopy. C. inopinata was found in all islands where F. septica figs were found. C.i nopinata was routinely found in the fig interior and almost never observed on the outside surface. C. inopinata was only found in pollinated figs, and C. inopinata was more likely to be observed in figs with more foundress pollinating wasps. Actively reproducing C. inopinata dominated early phase figs, whereas late phase figs with emerging wasp progeny harbored C. inopinata dauer larvae. Additionally, C. inopinata was observed dismounting from Ceratosolen pollinating wasps that were placed on agar plates. C. inopinata was not found on non-pollinating, parasitic Philotrypesis wasps. Finally, C. inopinata was only observed in F. septica figs among five Okinawan Ficus species sampled.

CONCLUSION: These are the first detailed field observations of C. inopinata, and they suggest a natural history where this species proliferates in early phase F. septica figs and disperses from late phase figs on Ceratosolen pollinating fig wasps. While consistent with other examples of nematode diversification in the fig microcosm, the fig and wasp host specificity of C. inopinata is highly divergent from the life histories of its close relatives and frames hypotheses for future investigations. This natural co-occurrence of the fig/fig wasp and C. inopinata study systems sets the stage for an integrated research program that can help to explain the evolution of interspecific interactions.}, } @article {pmid30129174, year = {2018}, author = {Dell'Aglio, DD and Troscianko, J and McMillan, WO and Stevens, M and Jiggins, CD}, title = {The appearance of mimetic Heliconius butterflies to predators and conspecifics.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2156-2166}, pmid = {30129174}, issn = {1558-5646}, support = {339873//European Research Council/International ; 9423/11-7//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; //Cambridge Overseas Trust/ ; BB/G022887/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Smithsonian Tropical Research Institute/ ; Speciation Genetics 339873//European Research Council/International ; }, abstract = {Adaptive coloration is under conflicting selection pressures: choosing potential mates and warning signaling against visually guided predators. Different elements of the color signal may therefore be tuned by evolution for different functions. We investigated how mimicry in four pairs of Heliconius comimics is potentially seen both from the perspective of butterflies and birds. Visual sensitivities of eight candidate avian predators were predicted through genetic analysis of their opsin genes. Using digital image color analysis, combined with bird and butterfly visual system models, we explored how predators and conspecifics may visualize mimetic patterns. Ultraviolet vision (UVS) birds are able to discriminate between the yellow and white colors of comimics better than violet vision (VS) birds. For Heliconius vision, males and females differ in their ability to discriminate comimics. Female vision and red filtering pigments have a significant effect on the perception of the yellow forewing band and the red ventral forewing pattern. A behavioral experiment showed that UV cues are used in mating behavior; removal of such cues was associated with an increased tendency to approach comimics as compared to conspecifics. We have therefore shown that visual signals can act to both reduce the cost of confusion in courtship and maintain the advantages of mimicry.}, } @article {pmid30128842, year = {2018}, author = {Li, Y and Hou, XJ and Shen, X and Han, SB and Ju, Z and Zhao, Z and Yu, XY and Wu, M and Sun, C}, title = {Confluentibacter flavum sp. nov., Isolated from the Saline Lake.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1447-1452}, pmid = {30128842}, issn = {1432-0991}, support = {2017FY100300//Science & Technology Basic Resources Investigation Program of China/ ; 16042186-Y//the Science Foundation of Zhejiang Sci-Tech University/ ; Y201636535//a project supported by Scientific Research Fund of Zhejiang Provincial Education Department/ ; }, mesh = {Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry/metabolism ; Flavobacteriaceae/classification/genetics/*isolation & purification/metabolism ; Lakes/chemistry/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sodium Chloride/*analysis/metabolism ; }, abstract = {A Gram-stain-negative, rod-shaped, non-motile, bacterial isolate designated 3BT, was isolated from a saline lake, and subjected to a polyphasic taxonomic investigation. The phylogenetic analysis based on 16S rRNA gene sequence clearly showed an allocation to the genus Confluentibacter with similarity ranging from 95.1 to 98%. OrthoANI values between strain 3BT and related strains of Confluentibacter (< 90%) were lower than the threshold value of 95% ANI relatedness recommended for species demarcation. Strain 3BT grew at 4-35 °C and pH 6.0-8.0 (optimum, 28 °C and pH 6.5) and with 0-3% (w/v) NaCl (optimum, 0.5%). The predominant respiratory quinone was menaquinone-6 (MK-6) and the major fatty acids were iso-C15:0, iso-C15:1 G, iso-C15:0 3-OH, and iso-C17:0 3-OH. The polar lipid profile of strain 3BT comprised phosphatidylethanolamine, one unidentified aminolipid, one aminophospholipid, and three unidentified lipids (L1-3). The DNA G+C content was 33.1 mol%. On the basis of morphological, physiological, and chemotaxonomic characteristics, together with the results of phylogenetic analysis, strain 3BT is described as a novel species in genus Confluentibacter, for which the name Confluentibacter flavum sp. nov. (type strain 3BT = CGMCC115960T = KCTC52969T) is proposed.}, } @article {pmid30128841, year = {2018}, author = {Mouri, Y and Takada, Y}, title = {Contribution of Three Different Regions of Isocitrate Dehydrogenases from Psychrophilic and Psychrotolerant Bacteria to Their Thermal Properties.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1523-1529}, pmid = {30128841}, issn = {1432-0991}, mesh = {Alteromonadaceae/chemistry/*enzymology/genetics ; Bacterial Proteins/*chemistry/genetics/metabolism ; Enzyme Stability ; Isocitrate Dehydrogenase/*chemistry/genetics/metabolism ; Protein Domains ; Temperature ; }, abstract = {Monomeric isocitrate dehydrogenases of a psychrophilic bacterium, Colwellia maris, and a psychrotolerant bacterium, Pseudomonas psychrophila, (CmIDH and PpIDH) are cold-adapted and mesophilic, respectively. On the other hand, previous studies revealed that the monomeric IDH of Azotobacter vinelandii (AvIDH) is also mesophilic and the regions 2 and 3 among three regions of this enzyme are involved in the thermal properties. Therefore, to examine whether the region(s) responsible for the mesophilic properties are common between PpIDH and AvIDH, the genes of chimeric IDHs exchanging three regions of PpIDH and CmIDH in various combinations were constructed and overexpressed as His-tagged recombinant proteins in the Escherichia coli cells, and the chimeric and wild-type PpIDH and CmIDH were purified with Ni-chelating affinity column chromatography. The swapping chimeras of the regions 2 or 3 in PpIDH and CmIDH showed lower and higher optimum temperatures for activities and their thermostabilities than the wild-type ones, respectively. On the other hand, the exchange of the respective region 1 hardly influenced these properties of the two IDHs. Therefore, the regions 2 and 3 of the two IDHs were confirmed to be involved in their thermal properties. These results were coincident with those of the previous study on chimeric IDHs between AvIDH and CmIDH, indicating that the common regions of AvIDH and PpIDH are responsible for their mesophilic properties and the amino acid residues involved in their thermal properties are present in the regions 2 and 3.}, } @article {pmid30128840, year = {2018}, author = {Park, S and Choi, J and Park, JM and Yoon, JH}, title = {Pseudopontivivens aestuariicola gen. nov., sp. nov., a Novel Bacterium of the Class Alphaproteobacteria Isolated from a Tidal Flat.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1516-1522}, pmid = {30128840}, issn = {1432-0991}, support = {the project on survey of indigenous species of Korea//National Institute of Biological Resources/ ; PJ012956//Rural Development Administration/ ; }, mesh = {Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry/metabolism ; Geologic Sediments/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/classification/genetics/*isolation & purification/metabolism ; Seawater/*microbiology ; Sodium Chloride ; }, abstract = {A Gram-stain-negative, non-motile and coccoid, ovoid or rod-shaped bacterial strain, OITF-57T, which was isolated from a tidal flat sediment in South Korea, was characterized taxonomically. Strain OITF-57T grew optimally at 25 °C, at pH 7.0-8.0 and in the presence of 2.0% (w/v) NaCl. Strain OITF-57T exhibited the highest 16S rRNA gene sequence similarity value (94.2%) to the type strain of Pontivivens insulae forming a cluster in the neighbour-joining phylogenetic tree. In the maximum-likelihood and maximum-parsimony phylogenetic trees based on 16S rRNA gene sequences and the phylogenetic tress based on gyrB sequences, strain OITF-57T formed evolutionary lineages independent of those of other taxa. Strain OITF-57T contained Q-10 as the predominant ubiquinone and C18:1 ω7c as the major fatty acid. The major polar lipids of strain OITF-57T were phosphatidylcholine and phosphatidylglycerol. The DNA G + C content of strain OITF-57T was 66.0 mol%. The chemotaxonomic data and other differential phenotypic properties made it possible to distinguish strain OITF-57T from the genus Pontivivens and other phylogenetically related genera. On the basis of the data presented, strain OITF-57T constitutes a new genus and species within the class Alphaproteobacteria, for which the name Pseudopontivivens aestuariicola gen. nov., sp. nov. is proposed. The type strain is OITF-57T (= KACC 19570T = CGMCC 1.13481T).}, } @article {pmid30127539, year = {2018}, author = {Betts, HC and Puttick, MN and Clark, JW and Williams, TA and Donoghue, PCJ and Pisani, D}, title = {Integrated genomic and fossil evidence illuminates life's early evolution and eukaryote origin.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1556-1562}, pmid = {30127539}, issn = {2397-334X}, abstract = {Establishing a unified timescale for the early evolution of Earth and life is challenging and mired in controversy because of the paucity of fossil evidence, the difficulty of interpreting it and dispute over the deepest branching relationships in the tree of life. Surprisingly, it remains perhaps the only episode in the history of life where literal interpretations of the fossil record hold sway, revised with every new discovery and reinterpretation. We derive a timescale of life, combining a reappraisal of the fossil material with new molecular clock analyses. We find the last universal common ancestor of cellular life to have predated the end of late heavy bombardment (>3.9 billion years ago (Ga)). The crown clades of the two primary divisions of life, Eubacteria and Archaebacteria, emerged much later (<3.4 Ga), relegating the oldest fossil evidence for life to their stem lineages. The Great Oxidation Event significantly predates the origin of modern Cyanobacteria, indicating that oxygenic photosynthesis evolved within the cyanobacterial stem lineage. Modern eukaryotes do not constitute a primary lineage of life and emerged late in Earth's history (<1.84 Ga), falsifying the hypothesis that the Great Oxidation Event facilitated their radiation. The symbiotic origin of mitochondria at 2.053-1.21 Ga reflects a late origin of the total-group Alphaproteobacteria to which the free living ancestor of mitochondria belonged.}, } @article {pmid30127538, year = {2018}, author = {Hennenberg, KJ and Böttcher, H and Bradshaw, CJA}, title = {Revised European Union renewable-energy policies erode nature protection.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1519-1520}, doi = {10.1038/s41559-018-0659-3}, pmid = {30127538}, issn = {2397-334X}, } @article {pmid30127537, year = {2018}, author = {Audzijonyte, A and Pecl, GT}, title = {Deep impact of fisheries.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1348-1349}, doi = {10.1038/s41559-018-0653-9}, pmid = {30127537}, issn = {2397-334X}, } @article {pmid30127528, year = {2018}, author = {Durbin, AD and Zimmerman, MW and Dharia, NV and Abraham, BJ and Iniguez, AB and Weichert-Leahey, N and He, S and Krill-Burger, JM and Root, DE and Vazquez, F and Tsherniak, A and Hahn, WC and Golub, TR and Young, RA and Look, AT and Stegmaier, K}, title = {Selective gene dependencies in MYCN-amplified neuroblastoma include the core transcriptional regulatory circuitry.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1240-1246}, doi = {10.1038/s41588-018-0191-z}, pmid = {30127528}, issn = {1546-1718}, abstract = {Childhood high-risk neuroblastomas with MYCN gene amplification are difficult to treat effectively1. This has focused attention on tumor-specific gene dependencies that underlie tumorigenesis and thus provide valuable targets for the development of novel therapeutics. Using unbiased genome-scale CRISPR-Cas9 approaches to detect genes involved in tumor cell growth and survival2-6, we identified 147 candidate gene dependencies selective for MYCN-amplified neuroblastoma cell lines, compared to over 300 other human cancer cell lines. We then used genome-wide chromatin-immunoprecipitation coupled to high-throughput sequencing analysis to demonstrate that a small number of essential transcription factors-MYCN, HAND2, ISL1, PHOX2B, GATA3, and TBX2-are members of the transcriptional core regulatory circuitry (CRC) that maintains cell state in MYCN-amplified neuroblastoma. To disable the CRC, we tested a combination of BRD4 and CDK7 inhibitors, which act synergistically, in vitro and in vivo, with rapid downregulation of CRC transcription factor gene expression. This study defines a set of critical dependency genes in MYCN-amplified neuroblastoma that are essential for cell state and survival in this tumor.}, } @article {pmid30127527, year = {2018}, author = {Castel, SE and Cervera, A and Mohammadi, P and Aguet, F and Reverter, F and Wolman, A and Guigo, R and Iossifov, I and Vasileva, A and Lappalainen, T}, title = {Modified penetrance of coding variants by cis-regulatory variation contributes to disease risk.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1327-1334}, pmid = {30127527}, issn = {1546-1718}, support = {HHSN268201000009C/HL/NHLBI NIH HHS/United States ; R01 MH106842/MH/NIMH NIH HHS/United States ; UM1 HG008901/HG/NHGRI NIH HHS/United States ; K99 HG009916/HG/NHGRI NIH HHS/United States ; R01 GM122924/GM/NIGMS NIH HHS/United States ; U24 DK112331/DK/NIDDK NIH HHS/United States ; HHSN268201000029C/HL/NHLBI NIH HHS/United States ; R01 MH101814/MH/NIMH NIH HHS/United States ; HHSN268201000002C/HL/NHLBI NIH HHS/United States ; }, abstract = {Coding variants represent many of the strongest associations between genotype and phenotype; however, they exhibit inter-individual differences in effect, termed 'variable penetrance'. Here, we study how cis-regulatory variation modifies the penetrance of coding variants. Using functional genomic and genetic data from the Genotype-Tissue Expression Project (GTEx), we observed that in the general population, purifying selection has depleted haplotype combinations predicted to increase pathogenic coding variant penetrance. Conversely, in cancer and autism patients, we observed an enrichment of penetrance increasing haplotype configurations for pathogenic variants in disease-implicated genes, providing evidence that regulatory haplotype configuration of coding variants affects disease risk. Finally, we experimentally validated this model by editing a Mendelian single-nucleotide polymorphism (SNP) using CRISPR/Cas9 on distinct expression haplotypes with the transcriptome as a phenotypic readout. Our results demonstrate that joint regulatory and coding variant effects are an important part of the genetic architecture of human traits and contribute to modified penetrance of disease-causing variants.}, } @article {pmid30127496, year = {2018}, author = {Marapana, DS and Dagley, LF and Sandow, JJ and Nebl, T and Triglia, T and Pasternak, M and Dickerman, BK and Crabb, BS and Gilson, PR and Webb, AI and Boddey, JA and Cowman, AF}, title = {Plasmepsin V cleaves malaria effector proteins in a distinct endoplasmic reticulum translocation interactome for export to the erythrocyte.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1010-1022}, doi = {10.1038/s41564-018-0219-2}, pmid = {30127496}, issn = {2058-5276}, abstract = {Plasmodium falciparum exports hundreds of virulence proteins within infected erythrocytes, a process that requires cleavage of a pentameric motif called Plasmodium export element or vacuolar transport signal by the endoplasmic reticulum (ER)-resident protease plasmepsin V. We identified plasmepsin V-binding proteins that form a unique interactome required for the translocation of effector cargo into the parasite ER. These interactions are functionally distinct from the Sec61-signal peptidase complex required for the translocation of proteins destined for the classical secretory pathway. This interactome does not involve the signal peptidase (SPC21) and consists of PfSec61, PfSPC25, plasmepsin V and PfSec62, which is an essential component of the post-translational ER translocon. Together, they form a distinct portal for the recognition and translocation of a large subset of Plasmodium export element effector proteins into the ER, thereby remodelling the infected erythrocyte that is required for parasite survival and pathogenesis.}, } @article {pmid30127495, year = {2018}, author = {Ingle, DJ and Levine, MM and Kotloff, KL and Holt, KE and Robins-Browne, RM}, title = {Dynamics of antimicrobial resistance in intestinal Escherichia coli from children in community settings in South Asia and sub-Saharan Africa.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1063-1073}, doi = {10.1038/s41564-018-0217-4}, pmid = {30127495}, issn = {2058-5276}, abstract = {The dynamics of antimicrobial resistance (AMR) in developing countries are poorly understood, especially in community settings, due to a sparsity of data on AMR prevalence and genetics. We used a combination of phenotyping, genomics and antimicrobial usage data to investigate patterns of AMR amongst atypical enteropathogenic Escherichia coli (aEPEC) strains isolated from children younger than five years old in seven developing countries (four in sub-Saharan Africa and three in South Asia) over a three-year period. We detected high rates of AMR, with 65% of isolates displaying resistance to three or more drug classes. Whole-genome sequencing revealed a diversity of known genetic mechanisms for AMR that accounted for >95% of phenotypic resistance, with comparable rates amongst aEPEC strains associated with diarrhoea or asymptomatic carriage. Genetic determinants of AMR were associated with the geographic location of isolates, not E. coli lineage, and AMR genes were frequently co-located, potentially enabling the acquisition of multi-drug resistance in a single step. Comparison of AMR with antimicrobial usage data showed that the prevalence of resistance to fluoroquinolones and third-generation cephalosporins was correlated with usage, which was higher in South Asia than in Africa. This study provides much-needed insights into the frequency and mechanisms of AMR in intestinal E. coli in children living in community settings in developing countries.}, } @article {pmid30127494, year = {2018}, author = {Brophy, JAN and Triassi, AJ and Adams, BL and Renberg, RL and Stratis-Cullum, DN and Grossman, AD and Voigt, CA}, title = {Engineered integrative and conjugative elements for efficient and inducible DNA transfer to undomesticated bacteria.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1043-1053}, doi = {10.1038/s41564-018-0216-5}, pmid = {30127494}, issn = {2058-5276}, abstract = {Engineering microorganisms to promote human or plant health will require manipulation of robust bacteria that are capable of surviving in harsh, competitive environments. Genetic engineering of undomesticated bacteria can be limited by an inability to transfer DNA into the cell. Here we developed an approach based on the integrative and conjugative element from Bacillus subtilis (ICEBs1) to overcome this problem. A donor strain (XPORT) was built to transfer miniaturized integrative and conjugative elements (mini-ICEBs1) to undomesticated bacteria. The strain was engineered to enable inducible control over conjugation, to integrate delivered DNA into the chromosome of the recipient, to restrict spread of heterologous DNA through separation of the type IV secretion system from the transferred DNA, and to enable simple isolation of engineered bacteria through a D-alanine auxotrophy. Efficient DNA transfer (10-1 to 10-7 conjugation events per donor) is demonstrated using 35 Gram-positive strains isolated from humans (skin and gut) and soil. Mini-ICEBs1 was used to rapidly characterize the performance of an isopropyl-β-D-thiogalactoside (IPTG)-inducible reporter across dozens of strains and to transfer nitrogen fixation to four Bacillus species. Finally, XPORT was introduced to soil to demonstrate DNA transfer under non-ideal conditions.}, } @article {pmid30127493, year = {2018}, author = {Orchard, RC and Wilen, CB and Virgin, HW}, title = {Sphingolipid biosynthesis induces a conformational change in the murine norovirus receptor and facilitates viral infection.}, journal = {Nature microbiology}, volume = {3}, number = {10}, pages = {1109-1114}, pmid = {30127493}, issn = {2058-5276}, support = {K08 AI128043/AI/NIAID NIH HHS/United States ; K99 DK116666/DK/NIDDK NIH HHS/United States ; R01 AI127552/AI/NIAID NIH HHS/United States ; U19 AI109725/AI/NIAID NIH HHS/United States ; }, abstract = {Cellular susceptibility to viral infections is in part determined by the presence of a host cellular receptor. Here we use murine norovirus as a model to uncover an unappreciated connection between an intracellular lipid biosynthetic enzyme and a receptor conformation that is permissive for viral infection. The serine palmitoyltransferase complex is required for de novo sphingolipid biosynthesis and we find that its absence impairs the ability of murine norovirus to bind and enter cells. Although the serine palmitoyltransferase complex is dispensable for the surface expression of the norovirus receptor, CD300lf, serine palmitoyltransferase activity is required for CD300lf to adopt a conformation permissive for viral binding. Addition of extracellular ceramide to serine palmitoyltransferase-deficient cells chemically complements both the conformational changes of CD300lf and the cellular susceptibility to murine norovirus infection. Taken together, these data indicate that intracellular sphingolipid biosynthesis regulates the conformation of the murine norovirus receptor and therefore the tropism of murine norovirus. This indicates that intracellular biosynthetic pathways can regulate viral tropism even when the receptor for a virus is expressed on the target cell surface.}, } @article {pmid30127484, year = {2018}, author = {Coleman, P and Greene, L}, title = {David Pines (1924-2018).}, journal = {Nature}, volume = {560}, number = {7719}, pages = {432}, doi = {10.1038/d41586-018-05987-0}, pmid = {30127484}, issn = {1476-4687}, } @article {pmid30127483, year = {2018}, author = {Perkel, JM}, title = {Software training in Antarctica.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {515}, doi = {10.1038/d41586-018-06011-1}, pmid = {30127483}, issn = {1476-4687}, } @article {pmid30127482, year = {2018}, author = {Burstein, SM and Finch, CE}, title = {Longevity examined: an ancient Greek's very modern views on ageing.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {430}, doi = {10.1038/d41586-018-05986-1}, pmid = {30127482}, issn = {1476-4687}, } @article {pmid30127481, year = {2018}, author = {Perkel, JM}, title = {A toolkit for data transparency takes shape.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {513-515}, doi = {10.1038/d41586-018-05990-5}, pmid = {30127481}, issn = {1476-4687}, } @article {pmid30127480, year = {2018}, author = {Mountain, M and Cohen, A}, title = {Billion-dollar telescopes could end up beyond the reach of US astronomers.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {427-429}, doi = {10.1038/d41586-018-05985-2}, pmid = {30127480}, issn = {1476-4687}, } @article {pmid30127479, year = {2018}, author = {Gutiérrez, JS and Masero, JA}, title = {Save Spanish songbirds from illegal trapping.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {431}, doi = {10.1038/d41586-018-05962-9}, pmid = {30127479}, issn = {1476-4687}, mesh = {Animals ; Conservation of Natural Resources/economics/*legislation & jurisprudence ; *European Union ; *Finches ; Spain ; }, } @article {pmid30127478, year = {2018}, author = {Macpherson, AJ and Ganal-Vonarburg, SC}, title = {Checkpoint for gut microbes after birth.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {436-438}, doi = {10.1038/d41586-018-05861-z}, pmid = {30127478}, issn = {1476-4687}, mesh = {*Gastrointestinal Microbiome ; Selection, Genetic ; *Toll-Like Receptor 5 ; }, } @article {pmid30127477, year = {2018}, author = {Klein, AM}, title = {Technique to measure the expression dynamics of each gene in a single cell.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {434-435}, doi = {10.1038/d41586-018-05882-8}, pmid = {30127477}, issn = {1476-4687}, } @article {pmid30127476, year = {2018}, author = {Pollak, M}, title = {Diet boosts the effectiveness of a cancer drug.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {439-440}, doi = {10.1038/d41586-018-05871-x}, pmid = {30127476}, issn = {1476-4687}, } @article {pmid30127407, year = {2018}, author = {Gu, Y and Alt, EA and Wang, H and Li, X and Willard, AP and Johnson, JA}, title = {Publisher Correction: Photoswitching topology in polymer networks with metal-organic cages as crosslinks.}, journal = {Nature}, volume = {563}, number = {7729}, pages = {E17}, doi = {10.1038/s41586-018-0426-2}, pmid = {30127407}, issn = {1476-4687}, abstract = {The green arrow in Fig. 3 has been restored online.}, } @article {pmid30127406, year = {2018}, author = {Gu, Z and Pandya, S and Samanta, A and Liu, S and Xiao, G and Meyers, CJG and Damodaran, AR and Barak, H and Dasgupta, A and Saremi, S and Polemi, A and Wu, L and Podpirka, AA and Will-Cole, A and Hawley, CJ and Davies, PK and York, RA and Grinberg, I and Martin, LW and Spanier, JE}, title = {Resonant domain-wall-enhanced tunable microwave ferroelectrics.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {622-627}, doi = {10.1038/s41586-018-0434-2}, pmid = {30127406}, issn = {1476-4687}, abstract = {Ordering of ferroelectric polarization1 and its trajectory in response to an electric field2 are essential for the operation of non-volatile memories3, transducers4 and electro-optic devices5. However, for voltage control of capacitance and frequency agility in telecommunication devices, domain walls have long been thought to be a hindrance because they lead to high dielectric loss and hysteresis in the device response to an applied electric field6. To avoid these effects, tunable dielectrics are often operated under piezoelectric resonance conditions, relying on operation well above the ferroelectric Curie temperature7, where tunability is compromised. Therefore, there is an unavoidable trade-off between the requirements of high tunability and low loss in tunable dielectric devices, which leads to severe limitations on their figure of merit. Here we show that domain structure can in fact be exploited to obtain ultralow loss and exceptional frequency selectivity without piezoelectric resonance. We use intrinsically tunable materials with properties that are defined not only by their chemical composition, but also by the proximity and accessibility of thermodynamically predicted strain-induced, ferroelectric domain-wall variants8. The resulting gigahertz microwave tunability and dielectric loss are better than those of the best film devices by one to two orders of magnitude and comparable to those of bulk single crystals. The measured quality factors exceed the theoretically predicted zero-field intrinsic limit owing to domain-wall fluctuations, rather than field-induced piezoelectric oscillations, which are usually associated with resonance. Resonant frequency tuning across the entire L, S and C microwave bands (1-8 gigahertz) is achieved in an individual device-a range about 100 times larger than that of the best intrinsically tunable material. These results point to a rich phase space of possible nanometre-scale domain structures that can be used to surmount current limitations, and demonstrate a promising strategy for obtaining ultrahigh frequency agility and low-loss microwave devices.}, } @article {pmid30127345, year = {2018}, author = {Gilbert, JA and Stephens, B}, title = {Microbiology of the built environment.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {661-670}, doi = {10.1038/s41579-018-0065-5}, pmid = {30127345}, issn = {1740-1534}, abstract = {The built environment comprises all structures built by humans, including our homes, workplaces, schools and vehicles. As in any ecosystem on Earth, microorganisms have been found in every part of the built environment that has been studied. They exist in the air, on surfaces and on building materials, usually dispersed by humans, animals and outdoor sources. Those microbial communities and their metabolites have been implied to cause (or exacerbate) and prevent (or mitigate) human disease. In this Review, we outline the history of the field of microbiology of the built environment and discuss recent insights that have been gained into microbial ecology, adaptation and evolution of this ecosystem. Finally, we consider the implications of this research, specifically, how it is changing the types of materials we use in buildings and how our built environments affect human health.}, } @article {pmid30127035, year = {2018}, author = {Negi, J and Munemasa, S and Song, B and Tadakuma, R and Fujita, M and Azoulay-Shemer, T and Engineer, CB and Kusumi, K and Nishida, I and Schroeder, JI and Iba, K}, title = {Eukaryotic lipid metabolic pathway is essential for functional chloroplasts and CO2 and light responses in Arabidopsis guard cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {9038-9043}, pmid = {30127035}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/metabolism ; Biological Transport, Active/physiology ; Carbon Dioxide/*metabolism ; Chloroplasts/genetics/*metabolism ; *Light ; Lipid Metabolism/*physiology ; Mutation ; Plant Stomata/genetics/*metabolism ; Signal Transduction/*physiology ; }, abstract = {Stomatal guard cells develop unique chloroplasts in land plant species. However, the developmental mechanisms and function of chloroplasts in guard cells remain unclear. In seed plants, chloroplast membrane lipids are synthesized via two pathways: the prokaryotic and eukaryotic pathways. Here we report the central contribution of endoplasmic reticulum (ER)-derived chloroplast lipids, which are synthesized through the eukaryotic lipid metabolic pathway, in the development of functional guard cell chloroplasts. We gained insight into this pathway by isolating and examining an Arabidopsis mutant, gles1 (green less stomata 1), which had achlorophyllous stomatal guard cells and impaired stomatal responses to CO2 and light. The GLES1 gene encodes a small glycine-rich protein, which is a putative regulatory component of the trigalactosyldiacylglycerol (TGD) protein complex that mediates ER-to-chloroplast lipid transport via the eukaryotic pathway. Lipidomic analysis revealed that in the wild type, the prokaryotic pathway is dysfunctional, specifically in guard cells, whereas in gles1 guard cells, the eukaryotic pathway is also abrogated. CO2-induced stomatal closing and activation of guard cell S-type anion channels that drive stomatal closure were disrupted in gles1 guard cells. In conclusion, the eukaryotic lipid pathway plays an essential role in the development of a sensing/signaling machinery for CO2 and light in guard cell chloroplasts.}, } @article {pmid30127034, year = {2018}, author = {Ding, J and Yu, Q and Asta, M and Ritchie, RO}, title = {Tunable stacking fault energies by tailoring local chemical order in CrCoNi medium-entropy alloys.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8919-8924}, pmid = {30127034}, issn = {1091-6490}, abstract = {High-entropy alloys (HEAs) are an intriguing new class of metallic materials due to their unique mechanical behavior. Achieving a detailed understanding of structure-property relationships in these materials has been challenged by the compositional disorder that underlies their unique mechanical behavior. Accordingly, in this work, we employ first-principles calculations to investigate the nature of local chemical order and establish its relationship to the intrinsic and extrinsic stacking fault energy (SFE) in CrCoNi medium-entropy solid-solution alloys, whose combination of strength, ductility, and toughness properties approaches the best on record. We find that the average intrinsic and extrinsic SFE are both highly tunable, with values ranging from -43 to 30 mJ⋅m-2 and from -28 to 66 mJ⋅m-2, respectively, as the degree of local chemical order increases. The state of local ordering also strongly correlates with the energy difference between the face-centered cubic (fcc) and hexagonal close-packed (hcp) phases, which affects the occurrence of transformation-induced plasticity. This theoretical study demonstrates that chemical short-range order is thermodynamically favored in HEAs and can be tuned to affect the mechanical behavior of these alloys. It thus addresses the pressing need to establish robust processing-structure-property relationships to guide the science-based design of new HEAs with targeted mechanical behavior.}, } @article {pmid30127033, year = {2018}, author = {Min, YL and Jaichander, P and Sanchez-Ortiz, E and Bezprozvannaya, S and Malladi, VS and Cui, M and Wang, Z and Bassel-Duby, R and Olson, EN and Liu, N}, title = {Identification of a multipotent Twist2-expressing cell population in the adult heart.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8430-E8439}, pmid = {30127033}, issn = {1091-6490}, mesh = {Animals ; Drosophila melanogaster ; Endothelial Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Mice ; Mice, Transgenic ; Multipotent Stem Cells/cytology/*metabolism ; Myocardium/cytology/*metabolism ; Myocytes, Cardiac/cytology/metabolism ; Repressor Proteins/*biosynthesis/genetics ; Twist-Related Protein 1/*biosynthesis/genetics ; }, abstract = {Twist transcription factors function as ancestral regulators of mesodermal cell fates in organisms ranging from Drosophila to mammals. Through lineage tracing of Twist2 (Tw2)-expressing cells with tamoxifen-inducible Tw2-CreERT2 and tdTomato (tdTO) reporter mice, we discovered a unique cell population that progressively contributes to cardiomyocytes (CMs), endothelial cells, and fibroblasts in the adult heart. Clonal analysis confirmed the ability of Tw2-derived tdTO+ (Tw2-tdTO+) cells to form CMs in vitro. Within the adult heart, Tw2-tdTO+ CMs accounted for ∼13% of total CMs, the majority of which resulted from fusion of Tw2-tdTO+ cells with existing CMs. Tw2-tdTO+ cells also contribute to cardiac remodeling after injury. We conclude that Tw2-tdTO+ cells participate in lifelong maintenance of cardiac function, at least in part through de novo formation of CMs and fusion with preexisting CMs, as well as in the genesis of other cellular components of the adult heart.}, } @article {pmid30127032, year = {2018}, author = {Yu, H and Shen, C and Liu, Y and Menasche, BL and Ouyang, Y and Stowell, MHB and Shen, J}, title = {SNARE zippering requires activation by SNARE-like peptides in Sec1/Munc18 proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8421-E8429}, pmid = {30127032}, issn = {1091-6490}, support = {R01 DK095367/DK/NIDDK NIH HHS/United States ; R35 GM126960/GM/NIGMS NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; COS Cells ; Cercopithecus aethiops ; Exocytosis/*drug effects ; Kinetics ; Membrane Fusion/*drug effects ; Mice ; *Munc18 Proteins/chemistry/metabolism ; *Peptides/chemistry/pharmacology ; Rats ; *SNARE Proteins/chemistry/metabolism ; }, abstract = {Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) catalyze membrane fusion by forming coiled-coil bundles between membrane bilayers. The SNARE bundle zippers progressively toward the membranes, pulling the lipid bilayers into close proximity to fuse. In this work, we found that the +1 and +2 layers in the C-terminal domains (CTDs) of SNAREs are dispensable for reconstituted SNARE-mediated fusion reactions. By contrast, all CTD layers are required for fusion reactions activated by the cognate Sec1/Munc18 (SM) protein or a synthetic Vc peptide derived from the vesicular (v-) SNARE, correlating with strong acceleration of fusion kinetics. These results suggest a similar mechanism underlying the stimulatory functions of SM proteins and Vc peptide in SNARE-dependent membrane fusion. Unexpectedly, we identified a conserved SNARE-like peptide (SLP) in SM proteins that structurally and functionally resembles Vc peptide. Like Vc peptide, SLP binds and activates target (t-) SNAREs, accelerating the fusion reaction. Disruption of the t-SNARE-SLP interaction inhibits exocytosis in vivo. Our findings demonstrated that a t-SNARE-SLP intermediate must form before SNAREs can drive efficient vesicle fusion.}, } @article {pmid30127031, year = {2018}, author = {Pereyaslavets, L and Kurnikov, I and Kamath, G and Butin, O and Illarionov, A and Leontyev, I and Olevanov, M and Levitt, M and Kornberg, RD and Fain, B}, title = {On the importance of accounting for nuclear quantum effects in ab initio calibrated force fields in biological simulations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8878-8882}, pmid = {30127031}, issn = {1091-6490}, mesh = {*Models, Biological ; *Quantum Theory ; }, abstract = {In many important processes in chemistry, physics, and biology the nuclear degrees of freedom cannot be described using the laws of classical mechanics. At the same time, the vast majority of molecular simulations that employ wide-coverage force fields treat atomic motion classically. In light of the increasing desire for and accelerated development of quantum mechanics (QM)-parameterized interaction models, we reexamine whether the classical treatment is sufficient for a simple but crucial chemical species: alkanes. We show that when using an interaction model or force field in excellent agreement with the "gold standard" QM data, even very basic simulated properties of liquid alkanes, such as densities and heats of vaporization, deviate significantly from experimental values. Inclusion of nuclear quantum effects via techniques that treat nuclear degrees of freedom using the laws of classical mechanics brings the simulated properties much closer to reality.}, } @article {pmid30127030, year = {2018}, author = {Saez Cabezas, CA and Ong, GK and Jadrich, RB and Lindquist, BA and Agrawal, A and Truskett, TM and Milliron, DJ}, title = {Gelation of plasmonic metal oxide nanocrystals by polymer-induced depletion attractions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8925-8930}, pmid = {30127030}, issn = {1091-6490}, abstract = {Gelation of colloidal nanocrystals emerged as a strategy to preserve inherent nanoscale properties in multiscale architectures. However, available gelation methods to directly form self-supported nanocrystal networks struggle to reliably control nanoscale optical phenomena such as photoluminescence and localized surface plasmon resonance (LSPR) across nanocrystal systems due to processing variabilities. Here, we report on an alternative gelation method based on physical internanocrystal interactions: short-range depletion attractions balanced by long-range electrostatic repulsions. The latter are established by removing the native organic ligands that passivate tin-doped indium oxide (ITO) nanocrystals while the former are introduced by mixing with small PEG chains. As we incorporate increasing concentrations of PEG, we observe a reentrant phase behavior featuring two favorable gelation windows; the first arises from bridging effects while the second is attributed to depletion attractions according to phase behavior predicted by our unified theoretical model. Our assembled nanocrystals remain discrete within the gel network, based on X-ray scattering and high-resolution transmission electron microscopy. The infrared optical response of the gels is reflective of both the nanocrystal building blocks and the network architecture, being characteristic of ITO nanocrystals' LSPR with coupling interactions between neighboring nanocrystals.}, } @article {pmid30127029, year = {2018}, author = {Thornlow, BP and Hough, J and Roger, JM and Gong, H and Lowe, TM and Corbett-Detig, RB}, title = {Transfer RNA genes experience exceptionally elevated mutation rates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8996-9001}, pmid = {30127029}, issn = {1091-6490}, support = {R01 HG006753/HG/NHGRI NIH HHS/United States ; R35 GM128932/GM/NIGMS NIH HHS/United States ; T32 HG008345/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Arabidopsis/*genetics ; Drosophila melanogaster ; *Genes, Helminth ; *Genes, Plant ; Mice ; *Mutation ; RNA, Helminth/*genetics ; RNA, Plant/*genetics ; RNA, Transfer/*genetics ; }, abstract = {Transfer RNAs (tRNAs) are a central component for the biological synthesis of proteins, and they are among the most highly conserved and frequently transcribed genes in all living things. Despite their clear significance for fundamental cellular processes, the forces governing tRNA evolution are poorly understood. We present evidence that transcription-associated mutagenesis and strong purifying selection are key determinants of patterns of sequence variation within and surrounding tRNA genes in humans and diverse model organisms. Remarkably, the mutation rate at broadly expressed cytosolic tRNA loci is likely between 7 and 10 times greater than the nuclear genome average. Furthermore, evolutionary analyses provide strong evidence that tRNA genes, but not their flanking sequences, experience strong purifying selection acting against this elevated mutation rate. We also find a strong correlation between tRNA expression levels and the mutation rates in their immediate flanking regions, suggesting a simple method for estimating individual tRNA gene activity. Collectively, this study illuminates the extreme competing forces in tRNA gene evolution and indicates that mutations at tRNA loci contribute disproportionately to mutational load and have unexplored fitness consequences in human populations.}, } @article {pmid30127028, year = {2018}, author = {Martinez-Corral, R and Liu, J and Süel, GM and Garcia-Ojalvo, J}, title = {Bistable emergence of oscillations in growing Bacillus subtilis biofilms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8333-E8340}, pmid = {30127028}, issn = {1091-6490}, support = {R01 GM121888/GM/NIGMS NIH HHS/United States ; P50 GM085764/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bacillus subtilis/*physiology ; Biofilms/*growth & development ; Biological Clocks/*physiology ; *Models, Biological ; }, abstract = {Biofilm communities of Bacillus subtilis bacteria have recently been shown to exhibit collective growth-rate oscillations mediated by electrochemical signaling to cope with nutrient starvation. These oscillations emerge once the colony reaches a large enough number of cells. However, it remains unclear whether the amplitude of the oscillations, and thus their effectiveness, builds up over time gradually or if they can emerge instantly with a nonzero amplitude. Here we address this question by combining microfluidics-based time-lapse microscopy experiments with a minimal theoretical description of the system in the form of a delay-differential equation model. Analytical and numerical methods reveal that oscillations arise through a subcritical Hopf bifurcation, which enables instant high-amplitude oscillations. Consequently, the model predicts a bistable regime where an oscillating and a nonoscillating attractor coexist in phase space. We experimentally validate this prediction by showing that oscillations can be triggered by perturbing the media conditions, provided the biofilm size lies within an appropriate range. The model also predicts that the minimum size at which oscillations start decreases with stress, a fact that we also verify experimentally. Taken together, our results show that collective oscillations in cell populations can emerge suddenly with nonzero amplitude via a discontinuous transition.}, } @article {pmid30127027, year = {2018}, author = {Dyer, RB and Eller, MW}, title = {Dynamics of hemagglutinin-mediated membrane fusion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8655-8657}, pmid = {30127027}, issn = {1091-6490}, support = {F31 GM069036/GM/NIGMS NIH HHS/United States ; R01 GM053640/GM/NIGMS NIH HHS/United States ; }, mesh = {Hemagglutinin Glycoproteins, Influenza Virus ; *Hemagglutinins ; Hydrogen-Ion Concentration ; *Membrane Fusion ; Viral Fusion Proteins ; }, } @article {pmid30127026, year = {2018}, author = {Dejani, NN and Orlando, AB and Niño, VE and Penteado, LA and Verdan, FF and Bazzano, JMR and Codo, AC and Salina, ACG and Saraiva, AC and Avelar, MR and Spolidorio, LC and Serezani, CH and Medeiros, AI}, title = {Intestinal host defense outcome is dictated by PGE2 production during efferocytosis of infected cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8469-E8478}, pmid = {30127026}, issn = {1091-6490}, mesh = {Animals ; Citrobacter rodentium/*immunology ; Colitis/*immunology/microbiology/pathology ; Dendritic Cells/*immunology/microbiology/pathology ; Dinoprostone/*immunology ; Enterobacteriaceae Infections/*immunology/microbiology/pathology ; Female ; Intestines/*immunology/microbiology ; Macrophages/*immunology/microbiology/pathology ; Mice ; Receptors, Prostaglandin E, EP4 Subtype/immunology ; }, abstract = {Inflammatory responses are terminated by the clearance of dead cells, a process termed efferocytosis. A consequence of efferocytosis is the synthesis of the antiinflammatory mediators TGF-β, PGE2, and IL-10; however, the efferocytosis of infected cells favors Th17 responses by eliciting the synthesis of TGF-β, IL-6, and IL-23. Recently, we showed that the efferocytosis of apoptotic Escherichia coli-infected macrophages by dendritic cells triggers PGE2 production in addition to pro-Th17 cytokine expression. We therefore examined the role of PGE2 during Th17 differentiation and intestinal pathology. The efferocytosis of apoptotic E. coli-infected cells by dendritic cells promoted high levels of PGE2, which impaired IL-1R expression via the EP4-PKA pathway in T cells and consequently inhibited Th17 differentiation. The outcome of murine intestinal Citrobacter rodentium infection was dependent on the EP4 receptor. Infected mice treated with EP4 antagonist showed enhanced intestinal defense against C. rodentium compared with infected mice treated with vehicle control. Those results suggest that EP4 signaling during infectious colitis could be targeted as a way to enhance Th17 immunity and host defense.}, } @article {pmid30127025, year = {2018}, author = {Huppenkothen, D and Arendt, A and Hogg, DW and Ram, K and VanderPlas, JT and Rokem, A}, title = {Hack weeks as a model for data science education and collaboration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8872-8877}, pmid = {30127025}, issn = {1091-6490}, support = {R25 MH112480/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Information Dissemination ; *Interdisciplinary Studies ; *Models, Educational ; Science/*education ; *Universities ; }, abstract = {Across many scientific disciplines, methods for recording, storing, and analyzing data are rapidly increasing in complexity. Skillfully using data science tools that manage this complexity requires training in new programming languages and frameworks as well as immersion in new modes of interaction that foster data sharing, collaborative software development, and exchange across disciplines. Learning these skills from traditional university curricula can be challenging because most courses are not designed to evolve on time scales that can keep pace with rapidly shifting data science methods. Here, we present the concept of a hack week as an effective model offering opportunities for networking and community building, education in state-of-the-art data science methods, and immersion in collaborative project work. We find that hack weeks are successful at cultivating collaboration and facilitating the exchange of knowledge. Participants self-report that these events help them in both their day-to-day research as well as their careers. Based on our results, we conclude that hack weeks present an effective, easy-to-implement, fairly low-cost tool to positively impact data analysis literacy in academic disciplines, foster collaboration, and cultivate best practices.}, } @article {pmid30127024, year = {2018}, author = {Zhou, B and Hofmann, D and Pinkoviezky, I and Sober, SJ and Nemenman, I}, title = {Chance, long tails, and inference in a non-Gaussian, Bayesian theory of vocal learning in songbirds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8538-E8546}, pmid = {30127024}, issn = {1091-6490}, support = {R01 EB022872/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Learning/*physiology ; *Models, Biological ; Songbirds/*physiology ; Vocalization, Animal/*physiology ; }, abstract = {Traditional theories of sensorimotor learning posit that animals use sensory error signals to find the optimal motor command in the face of Gaussian sensory and motor noise. However, most such theories cannot explain common behavioral observations, for example, that smaller sensory errors are more readily corrected than larger errors and large abrupt (but not gradually introduced) errors lead to weak learning. Here, we propose a theory of sensorimotor learning that explains these observations. The theory posits that the animal controls an entire probability distribution of motor commands rather than trying to produce a single optimal command and that learning arises via Bayesian inference when new sensory information becomes available. We test this theory using data from a songbird, the Bengalese finch, that is adapting the pitch (fundamental frequency) of its song following perturbations of auditory feedback using miniature headphones. We observe the distribution of the sung pitches to have long, non-Gaussian tails, which, within our theory, explains the observed dynamics of learning. Further, the theory makes surprising predictions about the dynamics of the shape of the pitch distribution, which we confirm experimentally.}, } @article {pmid30127023, year = {2018}, author = {Vogelbaum, MA}, title = {Personalized therapeutic delivery in the neurosurgical operating room.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8846-8848}, pmid = {30127023}, issn = {1091-6490}, mesh = {Brain Neoplasms/*surgery ; *Genotype ; Glioma/*surgery ; Humans ; Operating Rooms ; *Precision Medicine ; }, } @article {pmid30127022, year = {2018}, author = {He, C and Hu, X and Weston, TA and Jung, RS and Sandhu, J and Huang, S and Heizer, P and Kim, J and Ellison, R and Xu, J and Kilburn, M and Bensinger, SJ and Riezman, H and Tontonoz, P and Fong, LG and Jiang, H and Young, SG}, title = {Macrophages release plasma membrane-derived particles rich in accessible cholesterol.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8499-E8508}, pmid = {30127022}, issn = {1091-6490}, support = {P01 HL090553/HL/NHLBI NIH HHS/United States ; R01 HL087228/HL/NHLBI NIH HHS/United States ; R35 HL139725/HL/NHLBI NIH HHS/United States ; F32 HL132471/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell-Derived Microparticles/*metabolism/ultrastructure ; Cholesterol/*metabolism ; Lipoproteins, HDL/*metabolism/ultrastructure ; Macrophages/*metabolism/ultrastructure ; Mice ; Mice, Knockout ; Microscopy, Electron ; RAW 264.7 Cells ; Spectrometry, Mass, Secondary Ion ; }, abstract = {Macrophages are generally assumed to unload surplus cholesterol through direct interactions between ABC transporters on the plasma membrane and HDLs, but they have also been reported to release cholesterol-containing particles. How macrophage-derived particles are formed and released has not been clear. To understand the genesis of macrophage-derived particles, we imaged mouse macrophages by EM and nanoscale secondary ion mass spectrometry (nanoSIMS). By scanning EM, we found that large numbers of 20- to 120-nm particles are released from the fingerlike projections (filopodia) of macrophages. These particles attach to the substrate, forming a "lawn" of particles surrounding macrophages. By nanoSIMS imaging we showed that these particles are enriched in the mobile and metabolically active accessible pool of cholesterol (detectable by ALO-D4, a modified version of a cholesterol-binding cytolysin). The cholesterol content of macrophage-derived particles was increased by loading the cells with cholesterol or by adding LXR and RXR agonists to the cell-culture medium. Incubating macrophages with HDL reduced the cholesterol content of macrophage-derived particles. We propose that release of accessible cholesterol-rich particles from the macrophage plasma membrane could assist in disposing of surplus cholesterol and increase the efficiency of cholesterol movement to HDL.}, } @article {pmid30127021, year = {2018}, author = {Abbott, JK and Lloyd-Smith, P and Willard, D and Adamowicz, W}, title = {Status-quo management of marine recreational fisheries undermines angler welfare.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8948-8953}, pmid = {30127021}, issn = {1091-6490}, mesh = {Fisheries/*economics/*legislation & jurisprudence ; Gulf of Mexico ; Humans ; United States ; }, abstract = {Recreational fisheries can have a significant impact on fish populations and can suffer from the same symptoms of open access as commercial fisheries. However, recreational fisheries receive little attention compared with their commercial counterparts. Regulations designed to allocate scarce fish, such as seasonal closures and bag limits, can result in significant losses of value to anglers. We provide an estimate of these foregone benefits by estimating the potential gains to implementing management reforms of the headboat portion of the recreational red snapper fishery in the US Gulf of Mexico. This fishery has suffered from a regulatory spiral of shortened seasons and lowered bag limits in spite of rebuilding stocks. We gather primary survey data of headboat anglers that elicit trip behavior and their planned number and seasonal distribution of trips under status-quo and alternative management approaches. We use these data to estimate a model of anglers' seasonal trip demand as a function of the ability to retain red snapper, bag limits, and fees. We find that a hypothetical rights-based policy, whereby vessels with secure rights to a portion of annual catch could offer their customers year-round fishing in exchange for lower per-angler retention and increased fees, could raise the average angler's welfare by $139/y. When placed in the global context of recreational fishing, these estimates suggest that status-quo management may deprive anglers of billions of dollars of lost economic value per year.}, } @article {pmid30127020, year = {2018}, author = {Turner, AJ and Fung, I and Naik, V and Horowitz, LW and Cohen, RC}, title = {Modulation of hydroxyl variability by ENSO in the absence of external forcing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8931-8936}, pmid = {30127020}, issn = {1091-6490}, abstract = {The hydroxyl radical (OH) is the primary oxidant in the troposphere, and the impact of its fluctuations on the methane budget has been disputed in recent years, however measurements of OH are insufficient to characterize global interannual fluctuations relevant for methane. Here, we use a 6,000-y control simulation of preindustrial conditions with a chemistry-climate model to quantify the natural variability in OH and internal feedbacks governing that variability. We find that, even in the absence of external forcing, maximum OH changes are 3.8 ± 0.8% over a decade, which is large in the context of the recent methane growth from 2007-2017. We show that the OH variability is not a white-noise process. A wavelet analysis indicates that OH variability exhibits significant feedbacks with the same periodicity as the El Niño-Southern Oscillation (ENSO). We find intrinsically generated modulation of the OH variability, suggesting that OH may show periods of rapid or no change in future decades that are solely due to the internal climate dynamics (as opposed to external forcings). An empirical orthogonal function analysis further indicates that ENSO is the dominant mode of OH variability, with the modulation of OH occurring primarily through lightning [Formula: see text] La Niña is associated with an increase in convection in the Tropical Pacific, which increases the simulated occurrence of lightning and allows for more OH production. Understanding this link between OH and ENSO may improve the predictability of the oxidative capacity of the troposphere and assist in elucidating the causes of current and historical trends in methane.}, } @article {pmid30127019, year = {2018}, author = {Gleick, PH}, title = {Transitions to freshwater sustainability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8863-8871}, pmid = {30127019}, issn = {1091-6490}, mesh = {*Fresh Water ; Water Supply/*economics ; }, abstract = {Fundamental transitions in natural resources technologies, institutions, and management approaches are often difficult to see in advance, or even in the midst, of actual changes. Such a transformation now appears to be underway for freshwater resources, driven by increasingly severe water-related crises around the world. These include mismatches between supply and demand; the continued failure to meet basic human needs for water and sanitation; expanding ecological degradation due to extraction of water from natural systems and human-caused climate changes; the development of new technologies for using, treating, monitoring, and reporting on water use; new conceptual work; and growing attention given to water issues by the public and scientific communities. Similar transitions, with additional implications for water, also appear to be underway in the energy and climate fields. For such transitions to be successful, it is important to understand what drives deep changes in the perceptions, management, and use of natural resources; the factors that encourage or discourage changes; and whether strategies can be developed to improve and accelerate those changes that lead to social, economic, and environmental sustainability goals. This paper addresses the concept of resource or environmental transitions in the context of freshwater; reviews theories, data, and frameworks for identifying and analyzing transitions; offers some examples; and identifies key policies to help manage effective and successful transitions.}, } @article {pmid30127018, year = {2018}, author = {Morgan, MJ and Fitzwalter, BE and Owens, CR and Powers, RK and Sottnik, JL and Gamez, G and Costello, JC and Theodorescu, D and Thorburn, A}, title = {Metastatic cells are preferentially vulnerable to lysosomal inhibition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8479-E8488}, pmid = {30127018}, issn = {1091-6490}, support = {P30 CA046934/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Line, Tumor ; Chloroquine/*pharmacology ; Drug Resistance, Neoplasm/*drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Inhibitor of Differentiation Proteins/biosynthesis ; *Lung Neoplasms/drug therapy/metabolism/pathology/secondary ; Lysosomes/*metabolism/pathology ; Macrolides/*pharmacology ; Mice ; Neoplasm Metastasis ; Neoplasm Proteins/biosynthesis ; *Urinary Bladder Neoplasms/drug therapy/genetics/metabolism/pathology ; }, abstract = {Molecular alterations that confer phenotypic advantages to tumors can also expose specific therapeutic vulnerabilities. To search for potential treatments that would selectively affect metastatic cells, we examined the sensitivity of lineage-related human bladder cancer cell lines with different lung colonization abilities to chloroquine (CQ) or bafilomycin A1, which are inhibitors of lysosome function and autophagy. Both CQ and bafilomycin A1 were more cytotoxic in vitro to highly metastatic cells compared with their less metastatic counterparts. Genetic inactivation of macroautophagy regulators and lysosomal proteins indicated that this was due to greater reliance on the lysosome but not upon macroautophagy. To identify the mechanism underlying these effects, we generated cells resistant to CQ in vitro. Surprisingly, selection for in vitro CQ resistance was sufficient to alter gene expression patterns such that unsupervised cluster analysis of whole-transcriptome data indicated that selection for CQ resistance alone created tumor cells that were more similar to the poorly metastatic parental cells from which the metastatic cells were derived; importantly, these tumor cells also had diminished metastatic ability in vivo. These effects were mediated in part by differential expression of the transcriptional regulator ID4 (inhibitor of DNA binding 4); depletion of ID4 both promoted in vitro CQ sensitivity and restored lung colonization and metastasis of CQ-resistant cells. These data demonstrate that selection for metastasis ability confers selective vulnerability to lysosomal inhibitors and identify ID4 as a potential biomarker for the use of lysosomal inhibitors to reduce metastasis in patients.}, } @article {pmid30127017, year = {2018}, author = {Henderson, AR and Henley, MJ and Foster, NJ and Peiffer, AL and Beyersdorf, MS and Stanford, KD and Sturlis, SM and Linhares, BM and Hill, ZB and Wells, JA and Cierpicki, T and Brooks, CL and Fierke, CA and Mapp, AK}, title = {Conservation of coactivator engagement mechanism enables small-molecule allosteric modulators.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8960-8965}, pmid = {30127017}, issn = {1091-6490}, mesh = {Allosteric Regulation/physiology ; Humans ; Mediator Complex/*antagonists & inhibitors/*chemistry/metabolism ; Peptides/*chemistry ; Protein Domains ; Protein Structure, Quaternary ; Protein Structure, Secondary ; }, abstract = {Transcriptional coactivators are a molecular recognition marvel because a single domain within these proteins, the activator binding domain or ABD, interacts with multiple compositionally diverse transcriptional activators. Also remarkable is the structural diversity among ABDs, which range from conformationally dynamic helical motifs to those with a stable core such as a β-barrel. A significant objective is to define conserved properties of ABDs that allow them to interact with disparate activator sequences. The ABD of the coactivator Med25 (activator interaction domain or AcID) is unique in that it contains secondary structural elements that are on both ends of the spectrum: helices and loops that display significant conformational mobility and a seven-stranded β-barrel core that is structurally rigid. Using biophysical approaches, we build a mechanistic model of how AcID forms binary and ternary complexes with three distinct activators; despite its static core, Med25 forms short-lived, conformationally mobile, and structurally distinct complexes with each of the cognate partners. Further, ternary complex formation is facilitated by allosteric communication between binding surfaces on opposing faces of the β-barrel. The model emerging suggests that the conformational shifts and cooperative binding is mediated by a flexible substructure comprised of two dynamic helices and flanking loops, indicating a conserved mechanistic model of activator engagement across ABDs. Targeting a region of this substructure with a small-molecule covalent cochaperone modulates ternary complex formation. Our data support a general strategy for the identification of allosteric small-molecule modulators of ABDs, which are key targets for mechanistic studies as well as therapeutic applications.}, } @article {pmid30127016, year = {2018}, author = {Hildebrand, EA and Grillo, KM and Sawchuk, EA and Pfeiffer, SK and Conyers, LB and Goldstein, ST and Hill, AC and Janzen, A and Klehm, CE and Helper, M and Kiura, P and Ndiema, E and Ngugi, C and Shea, JJ and Wang, H}, title = {A monumental cemetery built by eastern Africa's first herders near Lake Turkana, Kenya.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8942-8947}, pmid = {30127016}, issn = {1091-6490}, mesh = {*Archaeology ; *Funeral Rites ; History, Ancient ; Humans ; Kenya ; }, abstract = {Monumental architecture is a prime indicator of social complexity, because it requires many people to build a conspicuous structure commemorating shared beliefs. Examining monumentality in different environmental and economic settings can reveal diverse reasons for people to form larger social units and express unity through architectural display. In multiple areas of Africa, monumentality developed as mobile herders created large cemeteries and practiced other forms of commemoration. The motives for such behavior in sparsely populated, unpredictable landscapes may differ from well-studied cases of monumentality in predictable environments with sedentary populations. Here we report excavations and ground-penetrating radar surveys at the earliest and most massive monumental site in eastern Africa. Lothagam North Pillar Site was a communal cemetery near Lake Turkana (northwest Kenya) constructed 5,000 years ago by eastern Africa's earliest pastoralists. Inside a platform ringed by boulders, a 119.5-m2 mortuary cavity accommodated an estimated minimum of 580 individuals. People of diverse ages and both sexes were buried, and ornaments accompanied most individuals. There is no evidence for social stratification. The uncertainties of living on a "moving frontier" of early herding-exacerbated by dramatic environmental shifts-may have spurred people to strengthen social networks that could provide information and assistance. Lothagam North Pillar Site would have served as both an arena for interaction and a tangible reminder of shared identity.}, } @article {pmid30127015, year = {2018}, author = {Loy, DE and Plenderleith, LJ and Sundararaman, SA and Liu, W and Gruszczyk, J and Chen, YJ and Trimboli, S and Learn, GH and MacLean, OA and Morgan, ALK and Li, Y and Avitto, AN and Giles, J and Calvignac-Spencer, S and Sachse, A and Leendertz, FH and Speede, S and Ayouba, A and Peeters, M and Rayner, JC and Tham, WH and Sharp, PM and Hahn, BH}, title = {Evolutionary history of human Plasmodium vivax revealed by genome-wide analyses of related ape parasites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8450-E8459}, pmid = {30127015}, issn = {1091-6490}, support = {R01 AI097137/AI/NIAID NIH HHS/United States ; T32 AI007532/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; R01 AI091595/AI/NIAID NIH HHS/United States ; BB/M010996/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; R37 AI050529/AI/NIAID NIH HHS/United States ; 208693/Z/17/Z//Wellcome Trust/United Kingdom ; 108905/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cameroon ; Cote d'Ivoire ; *Evolution, Molecular ; Female ; Gabon ; *Genome-Wide Association Study ; Gorilla gorilla ; Humans ; Male ; Pan troglodytes ; Plasmodium vivax/*genetics ; *Polymorphism, Genetic ; Protozoan Proteins/*genetics/metabolism ; Pseudogenes ; *Selection, Genetic ; }, abstract = {Wild-living African apes are endemically infected with parasites that are closely related to human Plasmodium vivax, a leading cause of malaria outside Africa. This finding suggests that the origin of P. vivax was in Africa, even though the parasite is now rare in humans there. To elucidate the emergence of human P. vivax and its relationship to the ape parasites, we analyzed genome sequence data of P. vivax strains infecting six chimpanzees and one gorilla from Cameroon, Gabon, and Côte d'Ivoire. We found that ape and human parasites share nearly identical core genomes, differing by only 2% of coding sequences. However, compared with the ape parasites, human strains of P. vivax exhibit about 10-fold less diversity and have a relative excess of nonsynonymous nucleotide polymorphisms, with site-frequency spectra suggesting they are subject to greatly relaxed purifying selection. These data suggest that human P. vivax has undergone an extreme bottleneck, followed by rapid population expansion. Investigating potential host-specificity determinants, we found that ape P. vivax parasites encode intact orthologs of three reticulocyte-binding protein genes (rbp2d, rbp2e, and rbp3), which are pseudogenes in all human P. vivax strains. However, binding studies of recombinant RBP2e and RBP3 proteins to human, chimpanzee, and gorilla erythrocytes revealed no evidence of host-specific barriers to red blood cell invasion. These data suggest that, from an ancient stock of P. vivax parasites capable of infecting both humans and apes, a severely bottlenecked lineage emerged out of Africa and underwent rapid population growth as it spread globally.}, } @article {pmid30127014, year = {2018}, author = {}, title = {Correction for Mitchell et al., Nongenetic origins of cell-to-cell variability in B lymphocyte proliferation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8578}, doi = {10.1073/pnas.1813215115}, pmid = {30127014}, issn = {1091-6490}, } @article {pmid30127013, year = {2018}, author = {Speare, L and Cecere, AG and Guckes, KR and Smith, S and Wollenberg, MS and Mandel, MJ and Miyashiro, T and Septer, AN}, title = {Bacterial symbionts use a type VI secretion system to eliminate competitors in their natural host.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8528-E8537}, pmid = {30127013}, issn = {1091-6490}, support = {R00 GM097032/GM/NIGMS NIH HHS/United States ; R35 GM119627/GM/NIGMS NIH HHS/United States ; R21 AI117262/AI/NIAID NIH HHS/United States ; }, mesh = {Aliivibrio fischeri/isolation & purification/*physiology ; Animals ; Decapodiformes/*microbiology ; Symbiosis/*physiology ; *Type IV Secretion Systems/genetics/metabolism ; }, abstract = {Intraspecific competition describes the negative interaction that occurs when different populations of the same species attempt to fill the same niche. Such competition is predicted to occur among host-associated bacteria but has been challenging to study in natural biological systems. Although many bioluminescent Vibrio fischeri strains exist in seawater, only a few strains are found in the light-organ crypts of an individual wild-caught Euprymna scolopes squid, suggesting a possible role for intraspecific competition during early colonization. Using a culture-based assay to investigate the interactions of different V. fischeri strains, we found "lethal" and "nonlethal" isolates that could kill or not kill the well-studied light-organ isolate ES114, respectively. The killing phenotype of these lethal strains required a type VI secretion system (T6SS) encoded in a 50-kb genomic island. Multiple lethal and nonlethal strains could be cultured from the light organs of individual wild-caught adult squid. Although lethal strains eliminate nonlethal strains in vitro, two lethal strains could coexist in interspersed microcolonies that formed in a T6SS-dependent manner. This coexistence was destabilized upon physical mixing, resulting in one lethal strain consistently eliminating the other. When juvenile squid were coinoculated with lethal and nonlethal strains, they occupied different crypts, yet they were observed to coexist within crypts when T6SS function was disrupted. These findings, using a combination of natural isolates and experimental approaches in vitro and in the animal host, reveal the importance of T6SS in spatially separating strains during the establishment of host colonization in a natural symbiosis.}, } @article {pmid30127012, year = {2018}, author = {Carmona, EM and Larsson, HP and Neely, A and Alvarez, O and Latorre, R and Gonzalez, C}, title = {Gating charge displacement in a monomeric voltage-gated proton (Hv1) channel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9240-9245}, pmid = {30127012}, issn = {1091-6490}, support = {R01 GM109762/GM/NIGMS NIH HHS/United States ; R01 HL095920/HL/NHLBI NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Animals ; Ciona intestinalis/*chemistry/genetics/*metabolism ; Ion Channel Gating/*physiology ; Ion Channels/genetics/*metabolism ; Ion Transport/physiology ; Kinetics ; Mutation, Missense ; Xenopus laevis ; }, abstract = {The voltage-gated proton (Hv1) channel, a voltage sensor and a conductive pore contained in one structural module, plays important roles in many physiological processes. Voltage sensor movements can be directly detected by measuring gating currents, and a detailed characterization of Hv1 charge displacements during channel activation can help to understand the function of this channel. We succeeded in detecting gating currents in the monomeric form of the Ciona-Hv1 channel. To decrease proton currents and better separate gating currents from ion currents, we used the low-conducting Hv1 mutant N264R. Isolated ON-gating currents decayed at increasing rates with increasing membrane depolarization, and the amount of gating charges displaced saturates at high voltages. These are two hallmarks of currents arising from the movement of charged elements within the boundaries of the cell membrane. The kinetic analysis of gating currents revealed a complex time course of the ON-gating current characterized by two peaks and a marked Cole-Moore effect. Both features argue that the voltage sensor undergoes several voltage-dependent conformational changes during activation. However, most of the charge is displaced in a single central transition. Upon voltage sensor activation, the charge is trapped, and only a fast component that carries a small percentage of the total charge is observed in the OFF. We hypothesize that trapping is due to the presence of the arginine side chain in position 264, which acts as a blocking ion. We conclude that the movement of the voltage sensor must proceed through at least five states to account for our experimental data satisfactorily.}, } @article {pmid30127011, year = {2018}, author = {Swick, SM and Zhu, W and Matta, M and Aldrich, TJ and Harbuzaru, A and Lopez Navarrete, JT and Ponce Ortiz, R and Kohlstedt, KL and Schatz, GC and Facchetti, A and Melkonyan, FS and Marks, TJ}, title = {Closely packed, low reorganization energy π-extended postfullerene acceptors for efficient polymer solar cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8341-E8348}, pmid = {30127011}, issn = {1091-6490}, abstract = {New organic semiconductors are essential for developing inexpensive, high-efficiency, solution-processable polymer solar cells (PSCs). PSC photoactive layers are typically fabricated by film-casting a donor polymer and a fullerene acceptor blend, with ensuing solvent evaporation and phase separation creating discrete conduits for photogenerated holes and electrons. Until recently, n-type fullerene acceptors dominated the PSC literature; however, indacenodithienothiophene (IDTT)-based acceptors have recently enabled remarkable PSC performance metrics, for reasons that are not entirely obvious. We report two isomeric IDTT-based acceptors 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-benz-(5, 6)indanone))-5,5,11,11-tetrakis(4-nonylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']di-thiophene (ITN-C9) and 3,9-bis(2-methylene-(3-(1,1-dicyanomethylene)-benz(6,7)indanone))-5,5,11,11-tetrakis(4-nonylphenyl)-dithieno[2,3-d:2',3'-d']-s-indaceno[1,2-b:5,6-b']dithiophene (ITzN-C9) that shed light on the exceptional IDTT properties vis-à-vis fullerenes. The neat acceptors and blends with fluoropolymer donor poly{[4,8-bis[5-(2- ethylhexyl)-4-fluoro-2-thienyl]benzo[1,2-b:4,5-b']dithiophene2,6-diyl]-alt-[2,5-thiophenediyl[5,7-bis(2-ethylhexyl)-4,8-dioxo4H,8H-benzo[1,2-c:4,5-c']dithiophene-1,3-diyl]]} (PBDB-TF) are investigated by optical spectroscopy, cyclic voltammetry, thermogravimetric analysis, differential scanning calorimetry, single-crystal X-ray diffraction, photovoltaic response, space-charge-limited current transport, atomic force microscopy, grazing incidence wide-angle X-ray scattering, and density functional theory-level quantum chemical analysis. The data reveal that ITN-C9 and ITzN-C9 organize such that the lowest unoccupied molecular orbital-rich end groups have intermolecular π-π distances as close as 3.31(1) Å, with electronic coupling integrals as large as 38 meV, and internal reorganization energies as small as 0.133 eV, comparable to or superior to those in fullerenes. ITN-C9 and ITzN-C9 have broad solar-relevant optical absorption, and, when blended with PBDB-TF, afford devices with power conversion efficiencies near 10%. Performance differences between ITN-C9 and ITzN-C9 are understandable in terms of molecular and electronic structure distinctions via the influences on molecular packing and orientation with respect to the electrode.}, } @article {pmid30127010, year = {2018}, author = {Park, A and Tran, T and Atkinson, NS}, title = {Monitoring food preference in Drosophila by oligonucleotide tagging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {9020-9025}, pmid = {30127010}, issn = {1091-6490}, support = {R01 AA018037/AA/NIAAA NIH HHS/United States ; T32 AA007471/AA/NIAAA NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; }, mesh = {Animals ; Drosophila melanogaster ; Female ; Food Preferences/*physiology ; Male ; Mushroom Bodies/*physiology ; Oligonucleotides/*chemistry ; Polymerase Chain Reaction/*methods ; *Sex Characteristics ; }, abstract = {Drosophila melanogaster is a powerful model organism for dissecting the neurogenetic basis of appetitive and aversive behaviors. However, some methods used to assay food preference require or cause starvation. This can be problematic for fly ethanol research because it can be difficult to dissociate caloric preference for ethanol from pharmacological preference for the drug. We designed BARCODE, a starvation-independent assay that uses trace levels of oligonucleotide tags to differentially mark food types. In BARCODE, flies feed ad libitum, and relative food preference is monitored by qPCR of the oligonucleotides. Persistence of the ingested oligomers within the fly records the feeding history of the fly over several days. Using BARCODE, we identified a sexually dimorphic preference for ethanol. Females are attracted to ethanol-laden foods, whereas males avoid consuming it. Furthermore, genetically feminizing male mushroom body lobes induces preference for ethanol. In addition, we demonstrate that BARCODE can be used for multiplex diet measurements when animals are presented with more than two food choices.}, } @article {pmid30127009, year = {2018}, author = {}, title = {Correction for Caranto and Lancaster, Nitric oxide is an obligate bacterial nitrification intermediate produced by hydroxylamine oxidoreductase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8325}, doi = {10.1073/pnas.1812827115}, pmid = {30127009}, issn = {1091-6490}, } @article {pmid30127008, year = {2018}, author = {Sanz-Murillo, M and Xu, J and Belogurov, GA and Calvo, O and Gil-Carton, D and Moreno-Morcillo, M and Wang, D and Fernández-Tornero, C}, title = {Structural basis of RNA polymerase I stalling at UV light-induced DNA damage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8972-8977}, pmid = {30127008}, issn = {1091-6490}, support = {R01 GM102362/GM/NIGMS NIH HHS/United States ; }, mesh = {*DNA Damage ; DNA, Fungal/*chemistry/metabolism ; DNA, Ribosomal/*chemistry/metabolism ; RNA Polymerase I/*chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism ; *Ultraviolet Rays ; }, abstract = {RNA polymerase I (Pol I) transcribes ribosomal DNA (rDNA) to produce the ribosomal RNA (rRNA) precursor, which accounts for up to 60% of the total transcriptional activity in growing cells. Pol I monitors rDNA integrity and influences cell survival, but little is known about how this enzyme processes UV-induced lesions. We report the electron cryomicroscopy structure of Pol I in an elongation complex containing a cyclobutane pyrimidine dimer (CPD) at a resolution of 3.6 Å. The structure shows that the lesion induces an early translocation intermediate exhibiting unique features. The bridge helix residue Arg1015 plays a major role in CPD-induced Pol I stalling, as confirmed by mutational analysis. These results, together with biochemical data presented here, reveal the molecular mechanism of Pol I stalling by CPD lesions, which is distinct from Pol II arrest by CPD lesions. Our findings open the avenue to unravel the molecular mechanisms underlying cell endurance to lesions on rDNA.}, } @article {pmid30127007, year = {2018}, author = {Juraska, M and Magaret, CA and Shao, J and Carpp, LN and Fiore-Gartland, AJ and Benkeser, D and Girerd-Chambaz, Y and Langevin, E and Frago, C and Guy, B and Jackson, N and Duong Thi Hue, K and Simmons, CP and Edlefsen, PT and Gilbert, PB}, title = {Viral genetic diversity and protective efficacy of a tetravalent dengue vaccine in two phase 3 trials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8378-E8387}, pmid = {30127007}, issn = {1091-6490}, support = {R37 AI054165/AI/NIAID NIH HHS/United States ; }, mesh = {Age Factors ; Child ; Child, Preschool ; Dengue/genetics/immunology/*prevention & control ; Dengue Vaccines/*administration & dosage/genetics/immunology ; Dengue Virus/*genetics/immunology ; Female ; *Genetic Variation ; *Genotype ; Humans ; Male ; }, abstract = {Two phase 3 placebo-controlled trials of the CYD-TDV vaccine, evaluated in children aged 2-14 y (CYD14) and 9-16 y (CYD15), demonstrated vaccine efficacy (VE) of 56.5% and 60.8%, respectively, against symptomatic virologically confirmed dengue (VCD). Sieve analyses were conducted to evaluate whether and how VE varied with amino acid sequence features of dengue viruses (DENVs). DENV premembrane/envelope amino acid sequences from VCD endpoint cases were aligned with the vaccine insert sequences, and extensions of the proportional hazards model were applied to assess variation in VE with amino acid mismatch proportion distances from vaccine strains, individual amino acid residues, and phylogenetic genotypes. In CYD14, VE against VCD of any serotype (DENV-Any) decreased significantly with increasing amino acid distance from the vaccine, whereas in CYD15, VE against DENV-Any was distance-invariant. Restricting to the common age range and amino acid distance range between the trials and accounting for differential VE by serotype, however, showed no evidence of VE variation with distance in either trial. In serotype-specific analyses, VE against DENV4 decreased significantly with increasing amino acid distance from the DENV4 vaccine insert and was significantly greater against residue-matched DENV4 at eight signature positions. These effects were restricted to 2- to 8-y-olds, potentially because greater seropositivity of older children at baseline might facilitate a broader protective immune response. The relevance of an antigenic match between vaccine strains and circulating DENVs was also supported by greater estimated VE against serotypes and genotypes for which the circulating DENVs had shorter amino acid sequence distances from the vaccine.}, } @article {pmid30127006, year = {2018}, author = {Early, JO and Menon, D and Wyse, CA and Cervantes-Silva, MP and Zaslona, Z and Carroll, RG and Palsson-McDermott, EM and Angiari, S and Ryan, DG and Corcoran, SE and Timmons, G and Geiger, SS and Fitzpatrick, DJ and O'Connell, D and Xavier, RJ and Hokamp, K and O'Neill, LAJ and Curtis, AM}, title = {Circadian clock protein BMAL1 regulates IL-1β in macrophages via NRF2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8460-E8468}, pmid = {30127006}, issn = {1091-6490}, support = {205455//Wellcome Trust/United Kingdom ; }, mesh = {ARNTL Transcription Factors/genetics/*metabolism ; Animals ; HEK293 Cells ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism ; Inflammation/chemically induced/genetics/metabolism ; Interleukin-1beta/genetics/*metabolism ; Lipopolysaccharides/toxicity ; Macrophages/*metabolism/pathology ; Mice ; Mice, Knockout ; NF-E2-Related Factor 2/genetics/*metabolism ; *Oxidative Stress ; Reactive Oxygen Species/metabolism ; }, abstract = {A variety of innate immune responses and functions are dependent on time of day, and many inflammatory conditions are associated with dysfunctional molecular clocks within immune cells. However, the functional importance of these innate immune clocks has yet to be fully characterized. NRF2 plays a critical role in the innate immune system, limiting inflammation via reactive oxygen species (ROS) suppression and direct repression of the proinflammatory cytokines, IL-1β and IL-6. Here we reveal that the core molecular clock protein, BMAL1, controls the mRNA expression of Nrf2 via direct E-box binding to its promoter to regulate its activity. Deletion of Bmal1 decreased the response of NRF2 to LPS challenge, resulting in a blunted antioxidant response and reduced synthesis of glutathione. ROS accumulation was increased in Bmal1-/- macrophages, facilitating accumulation of the hypoxic response protein, HIF-1α. Increased ROS and HIF-1α levels, as well as decreased activity of NRF2 in cells lacking BMAL1, resulted in increased production of the proinflammatory cytokine, IL-1β. The excessive prooxidant and proinflammatory phenotype of Bmal1-/- macrophages was rescued by genetic and pharmacological activation of NRF2, or through addition of antioxidants. Our findings uncover a clear role for the molecular clock in regulating NRF2 in innate immune cells to control the inflammatory response. These findings provide insights into the pathology of inflammatory conditions, in which the molecular clock, oxidative stress, and IL-1β are known to play a role.}, } @article {pmid30127005, year = {2018}, author = {Cideciyan, AV and Sudharsan, R and Dufour, VL and Massengill, MT and Iwabe, S and Swider, M and Lisi, B and Sumaroka, A and Marinho, LF and Appelbaum, T and Rossmiller, B and Hauswirth, WW and Jacobson, SG and Lewin, AS and Aguirre, GD and Beltran, WA}, title = {Mutation-independent rhodopsin gene therapy by knockdown and replacement with a single AAV vector.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8547-E8556}, pmid = {30127005}, issn = {1091-6490}, support = {P30 EY001583/EY/NEI NIH HHS/United States ; P30 EY021721/EY/NEI NIH HHS/United States ; R01 EY006855/EY/NEI NIH HHS/United States ; R24 EY022012/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Dependovirus ; Dogs ; Gene Knock-In Techniques/*methods ; Gene Knockdown Techniques/*methods ; Genetic Therapy/*methods ; *Genetic Vectors ; HEK293 Cells ; Humans ; *RNA, Catalytic/biosynthesis/genetics ; Retinal Rod Photoreceptor Cells/*metabolism/pathology ; *Retinitis Pigmentosa/genetics/metabolism/pathology ; *Rhodopsin/biosynthesis/genetics ; }, abstract = {Inherited retinal degenerations are caused by mutations in >250 genes that affect photoreceptor cells or the retinal pigment epithelium and result in vision loss. For autosomal recessive and X-linked retinal degenerations, significant progress has been achieved in the field of gene therapy as evidenced by the growing number of clinical trials and the recent commercialization of the first gene therapy for a form of congenital blindness. However, despite significant efforts to develop a treatment for the most common form of autosomal dominant retinitis pigmentosa (adRP) caused by >150 mutations in the rhodopsin (RHO) gene, translation to the clinic has stalled. Here, we identified a highly efficient shRNA that targets human (and canine) RHO in a mutation-independent manner. In a single adeno-associated viral (AAV) vector we combined this shRNA with a human RHO replacement cDNA made resistant to RNA interference and tested this construct in a naturally occurring canine model of RHO-adRP. Subretinal vector injections led to nearly complete suppression of endogenous canine RHO RNA, while the human RHO replacement cDNA resulted in up to 30% of normal RHO protein levels. Noninvasive retinal imaging showed photoreceptors in treated areas were completely protected from retinal degeneration. Histopathology confirmed retention of normal photoreceptor structure and RHO expression in rod outer segments. Long-term (>8 mo) follow-up by retinal imaging and electroretinography indicated stable structural and functional preservation. The efficacy of this gene therapy in a clinically relevant large-animal model paves the way for treating patients with RHO-adRP.}, } @article {pmid30127004, year = {2018}, author = {Kong, Q and Lee, W and Lai, M and Bischak, CG and Gao, G and Wong, AB and Lei, T and Yu, Y and Wang, LW and Ginsberg, NS and Yang, P}, title = {Phase-transition-induced p-n junction in single halide perovskite nanowire.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8889-8894}, pmid = {30127004}, issn = {1091-6490}, abstract = {Semiconductor p-n junctions are fundamental building blocks for modern optical and electronic devices. The p- and n-type regions are typically created by chemical doping process. Here we show that in the new class of halide perovskite semiconductors, the p-n junctions can be readily induced through a localized thermal-driven phase transition. We demonstrate this p-n junction formation in a single-crystalline halide perovskite CsSnI3 nanowire (NW). This material undergoes a phase transition from a double-chain yellow (Y) phase to an orthorhombic black (B) phase. The formation energies of the cation and anion vacancies in these two phases are significantly different, which leads to n- and p- type electrical characteristics for Y and B phases, respectively. Interface formation between these two phases and directional interface propagation within a single NW are directly observed under cathodoluminescence (CL) microscopy. Current rectification is demonstrated for the p-n junction formed with this localized thermal-driven phase transition.}, } @article {pmid30127003, year = {2018}, author = {Tzeng, TC and Hasegawa, Y and Iguchi, R and Cheung, A and Caffrey, DR and Thatcher, EJ and Mao, W and Germain, G and Tamburro, ND and Okabe, S and Heneka, MT and Latz, E and Futai, K and Golenbock, DT}, title = {Inflammasome-derived cytokine IL18 suppresses amyloid-induced seizures in Alzheimer-prone mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {9002-9007}, pmid = {30127003}, issn = {1091-6490}, support = {R01 NS085215/NS/NINDS NIH HHS/United States ; UL1 TR001453/TR/NCATS NIH HHS/United States ; }, mesh = {Alzheimer Disease/drug therapy/genetics/*metabolism/pathology ; Amyloid/genetics/*metabolism ; Animals ; Inflammasomes/genetics/*metabolism ; Interleukin-18/genetics/*metabolism ; Interleukin-1beta/genetics/metabolism ; Levetiracetam ; Mice ; Mice, Knockout ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/metabolism ; Piracetam/analogs & derivatives/pharmacology ; Seizures/drug therapy/genetics/*metabolism/pathology ; *Synaptic Transmission ; }, abstract = {Alzheimer's disease (AD) is characterized by the progressive destruction and dysfunction of central neurons. AD patients commonly have unprovoked seizures compared with age-matched controls. Amyloid peptide-related inflammation is thought to be an important aspect of AD pathogenesis. We previously reported that NLRP3 inflammasome KO mice, when bred into APPswe/PS1ΔE9 (APP/PS1) mice, are completely protected from amyloid-induced AD-like disease, presumably because they cannot produce mature IL1β or IL18. To test the role of IL18, we bred IL18KO mice with APP/PS1 mice. Surprisingly, IL18KO/APP/PS1 mice developed a lethal seizure disorder that was completely reversed by the anticonvulsant levetiracetam. IL18-deficient AD mice showed a lower threshold in chemically induced seizures and a selective increase in gene expression related to increased neuronal activity. IL18-deficient AD mice exhibited increased excitatory synaptic proteins, spine density, and basal excitatory synaptic transmission that contributed to seizure activity. This study identifies a role for IL18 in suppressing aberrant neuronal transmission in AD.}, } @article {pmid30127002, year = {2018}, author = {Chen, B and Niu, J and Kreuzer, J and Zheng, B and Jarugumilli, GK and Haas, W and Wu, X}, title = {Auto-fatty acylation of transcription factor RFX3 regulates ciliogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8403-E8412}, pmid = {30127002}, issn = {1091-6490}, support = {R01 DK107651/DK/NIDDK NIH HHS/United States ; S10 RR027673/RR/NCRR NIH HHS/United States ; R01 CA181537/CA/NCI NIH HHS/United States ; }, mesh = {Acylation ; Animals ; Cilia/genetics/metabolism ; Ciliopathies/genetics/metabolism ; HEK293 Cells ; Humans ; *Lipoylation ; Mice ; NIH 3T3 Cells ; Oleic Acid/*metabolism ; Regulatory Factor X Transcription Factors/genetics/*metabolism ; Stearic Acids/*metabolism ; }, abstract = {Defects in cilia have been associated with an expanding human disease spectrum known as ciliopathies. Regulatory Factor X 3 (RFX3) is one of the major transcription factors required for ciliogenesis and cilia functions. In addition, RFX3 regulates pancreatic islet cell differentiation and mature β-cell functions. However, how RFX3 protein is regulated at the posttranslational level remains poorly understood. Using chemical reporters of protein fatty acylation and mass spectrometry analysis, here we show that RFX3 transcriptional activity is regulated by S-fatty acylation at a highly conserved cysteine residue in the dimerization domain. Surprisingly, RFX3 undergoes enzyme-independent, "self-catalyzed" auto-fatty acylation and displays preferences for 18-carbon stearic acid and oleic acid. The fatty acylation-deficient mutant of RFX3 shows decreased homodimerization; fails to promote ciliary gene expression, ciliogenesis, and elongation; and impairs Hedgehog signaling. Our findings reveal a regulation of RFX3 transcription factor and link fatty acid metabolism and protein lipidation to the regulation of ciliogenesis.}, } @article {pmid30127001, year = {2018}, author = {Takeuchi, H and Schneider, M and Williamson, DB and Ito, A and Takeuchi, M and Handford, PA and Haltiwanger, RS}, title = {Two novel protein O-glucosyltransferases that modify sites distinct from POGLUT1 and affect Notch trafficking and signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8395-E8402}, pmid = {30127001}, issn = {1091-6490}, support = {R01 GM061126/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Glucosyltransferases/genetics/*metabolism ; Glycosylation ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; Protein Transport/physiology ; Receptor, Notch1/genetics/*metabolism ; Receptor, Notch2/genetics/*metabolism ; Receptor, Notch3/genetics/*metabolism ; Repetitive Sequences, Amino Acid ; Signal Transduction/*physiology ; }, abstract = {The Notch-signaling pathway is normally activated by Notch-ligand interactions. A recent structural analysis suggested that a novel O-linked hexose modification on serine 435 of the mammalian NOTCH1 core ligand-binding domain lies at the interface with its ligands. This serine occurs between conserved cysteines 3 and 4 of Epidermal Growth Factor-like (EGF) repeat 11 of NOTCH1, a site distinct from those modified by protein O-glucosyltransferase 1 (POGLUT1), suggesting that a different enzyme is responsible. Here, we identify two novel protein O-glucosyltransferases, POGLUT2 and POGLUT3 (formerly KDELC1 and KDELC2, respectively), which transfer O-glucose (O-Glc) from UDP-Glc to serine 435. Mass spectrometric analysis of NOTCH1 produced in HEK293T cells lacking POGLUT2, POGLUT3, or both genes showed that either POGLUT2 or POGLUT3 can add this novel O-Glc modification. EGF11 of NOTCH2 does not have a serine residue in the same location for this O-glucosylation, but EGF10 of NOTCH3 (homologous to EGF11 in NOTCH1 and -2) is also modified at the same position. Comparison of the sites suggests a consensus sequence for modification. In vitro assays with POGLUT2 and POGLUT3 showed that both enzymes modified only properly folded EGF repeats and displayed distinct acceptor specificities toward NOTCH1 EGF11 and NOTCH3 EGF10. Mutation of the O-Glc modification site on EGF11 (serine 435) in combination with sensitizing O-fucose mutations in EGF8 or EGF12 affected cell-surface presentation of NOTCH1 or reduced activation of NOTCH1 by Delta-like1, respectively. This study identifies a previously undescribed mechanism for fine-tuning the Notch-signaling pathway in mammals.}, } @article {pmid30127000, year = {2018}, author = {Liu, P and Thomson, BR and Khalatyan, N and Feng, L and Liu, X and Savas, JN and Quaggin, SE and Jin, J}, title = {Selective permeability of mouse blood-aqueous barrier as determined by 15N-heavy isotope tracing and mass spectrometry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {9032-9037}, pmid = {30127000}, issn = {1091-6490}, support = {R00 DC013805/DC/NIDCD NIH HHS/United States ; R01 EY026286/EY/NEI NIH HHS/United States ; R01 EY025799/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Blood Proteins/*metabolism ; Blood-Retinal Barrier/*metabolism/pathology/physiopathology ; Cornea/metabolism/pathology/physiopathology ; Corneal Neovascularization/*metabolism/pathology/physiopathology ; Female ; Mice ; *Nitrogen Isotopes/pharmacokinetics/pharmacology ; Permeability ; Proteome/*metabolism ; *Water-Electrolyte Balance ; }, abstract = {The blood-aqueous barrier plays a key role in regulating aqueous humor homeostasis by selectively restricting passage of proteins into the eye. The kinetics of aqueous flow are traditionally measured using artificial markers; however, these marker molecules do not address the barrier's selective permeability to plasma proteins. Here we applied stable isotope labeling of all serum proteins with nitrogen-15 (15N) atoms. Following systemic injection of this "heavy" serum in mice, the 15N-to-endogenous nitrogen-14 (14N) ratio of each protein in aqueous was measured by mass spectrometry. By monitoring the kinetic changes in these ratios, we determined the permeability profiles of hundreds of serum proteins. Meanwhile, we subjected one of the eyes to neoangiogenic wound healing by inflicting injury to the corneal limbus and compared the 15N proteomes between the normal eyes and the recovering eyes at 2 weeks after injury. In the injured eye, we detected markedly enhanced permeability to inhibitory complement regulator proteins, such as Cfh, Cfhr, Cfb, Cfi, Cfd, and Vtn. Many of the proteins in this group are implicated in age-related macular degeneration associated with leakage of the blood-retinal barrier due to inflammation. To rule out the possibility that the observed leakage was due simply to physical damage of the blood vessels, we separately created a neovascularization model using an alkali burn of the avascular cornea. In this latter model, elevated levels of Cfh and Cfb were evident. These findings suggest that ocular neovascularization is associated with enhanced permeability to serum complement regulators.}, } @article {pmid30126999, year = {2018}, author = {Kaur, G and Tan, LX and Rathnasamy, G and La Cunza, N and Germer, CJ and Toops, KA and Fernandes, M and Blenkinsop, TA and Lakkaraju, A}, title = {Aberrant early endosome biogenesis mediates complement activation in the retinal pigment epithelium in models of macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {9014-9019}, pmid = {30126999}, issn = {1091-6490}, support = {P30 EY016665/EY/NEI NIH HHS/United States ; R01 EY023299/EY/NEI NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/deficiency ; Aged ; Aged, 80 and over ; Animals ; Ceramides/genetics/metabolism ; Complement C3a/genetics/*metabolism ; Disease Models, Animal ; Endosomes/genetics/*metabolism/pathology ; Female ; Humans ; Macular Degeneration/*congenital/genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Retinal Pigment Epithelium/*metabolism/pathology ; Swine ; TOR Serine-Threonine Kinases/genetics/*metabolism ; }, abstract = {Abnormally enlarged early endosomes (EEs) are pathological features of neurodegenerative diseases, yet insight into the mechanisms and consequences of EE expansion remains elusive. Here, we report swollen apical EEs in the retinal pigment epithelium (RPE) of aged human donors and in the pigmented Abca4-/- mouse model of Stargardt early-onset macular degeneration. Using high-resolution live-cell imaging, we show that age-related and pathological accumulation of lipofuscin bisretinoids increases ceramide at the apical surface of the RPE, which promotes inward budding and homotypic fusion of EEs. These enlarged endosomes internalize the complement protein C3 into the RPE, resulting in the intracellular generation of C3a fragments. Increased C3a in turn activates the mechanistic target of rapamycin (mTOR), a regulator of critical metabolic processes such as autophagy. The antidepressant desipramine, which decreases ceramide levels by inhibiting acid sphingomyelinase, corrects EE defects in the RPE of Abca4-/- mice. This prevents C3 internalization and limits the formation of C3a fragments within the RPE. Although uncontrolled complement activation is associated with macular degenerations, how complement contributes to pathology in a progressive disease is not well understood. Our studies link expansion of the EE compartment with intracellular complement generation and aberrant mTOR activation, which could set the stage for chronic metabolic reprogramming in the RPE as a prelude to disease. The pivotal role of ceramide in driving EE biogenesis and fusion in the Abca4-/- mice RPE suggests that therapeutic targeting of ceramide could be effective in Stargardt disease and other macular degenerations.}, } @article {pmid30126998, year = {2018}, author = {Chou, YM and Jiang, X and Liu, Q and Hu, HM and Wu, CC and Liu, J and Jiang, Z and Lee, TQ and Wang, CC and Song, YF and Chiang, CC and Tan, L and Lone, MA and Pan, Y and Zhu, R and He, Y and Chou, YC and Tan, AH and Roberts, AP and Zhao, X and Shen, CC}, title = {Multidecadally resolved polarity oscillations during a geomagnetic excursion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8913-8918}, pmid = {30126998}, issn = {1091-6490}, abstract = {Polarity reversals of the geomagnetic field have occurred through billions of years of Earth history and were first revealed in the early 20th century. Almost a century later, details of transitional field behavior during geomagnetic reversals and excursions remain poorly known. Here, we present a multidecadally resolved geomagnetic excursion record from a radioisotopically dated Chinese stalagmite at 107-91 thousand years before present with age precision of several decades. The duration of geomagnetic directional oscillations ranged from several centuries at 106-103 thousand years before present to millennia at 98-92 thousand years before present, with one abrupt reversal transition occurring in one to two centuries when the field was weakest. These features indicate prolonged geodynamo instability. Repeated asymmetrical interhemispheric polarity drifts associated with weak dipole fields likely originated in Earth's deep interior. If such rapid polarity changes occurred in future, they could severely affect satellites and human society.}, } @article {pmid30126997, year = {2018}, author = {Mummolo, J}, title = {Militarization fails to enhance police safety or reduce crime but may harm police reputation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {9181-9186}, pmid = {30126997}, issn = {1091-6490}, mesh = {*African Americans ; *Civil Rights ; *Crime ; Humans ; *Law Enforcement ; Maryland ; }, abstract = {The increasingly visible presence of heavily armed police units in American communities has stoked widespread concern over the militarization of local law enforcement. Advocates claim militarized policing protects officers and deters violent crime, while critics allege these tactics are targeted at racial minorities and erode trust in law enforcement. Using a rare geocoded census of SWAT team deployments from Maryland, I show that militarized police units are more often deployed in communities with large shares of African American residents, even after controlling for local crime rates. Further, using nationwide panel data on local police militarization, I demonstrate that militarized policing fails to enhance officer safety or reduce local crime. Finally, using survey experiments-one of which includes a large oversample of African American respondents-I show that seeing militarized police in news reports may diminish police reputation in the mass public. In the case of militarized policing, the results suggest that the often-cited trade-off between public safety and civil liberties is a false choice.}, } @article {pmid30126996, year = {2018}, author = {Li, S and Lucey, PG and Milliken, RE and Hayne, PO and Fisher, E and Williams, JP and Hurley, DM and Elphic, RC}, title = {Direct evidence of surface exposed water ice in the lunar polar regions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8907-8912}, pmid = {30126996}, issn = {1091-6490}, abstract = {Water ice may be allowed to accumulate in permanently shaded regions on airless bodies in the inner solar system such as Mercury, the Moon, and Ceres [Watson K, et al. (1961) J Geophys Res 66:3033-3045]. Unlike Mercury and Ceres, direct evidence for water ice exposed at the lunar surface has remained elusive. We utilize indirect lighting in regions of permanent shadow to report the detection of diagnostic near-infrared absorption features of water ice in reflectance spectra acquired by the Moon Mineralogy Mapper [M (3)] instrument. Several thousand M (3) pixels (∼280 × 280 m) with signatures of water ice at the optical surface (depth of less than a few millimeters) are identified within 20° latitude of both poles, including locations where independent measurements have suggested that water ice may be present. Most ice locations detected in M (3) data also exhibit lunar orbiter laser altimeter reflectance values and Lyman Alpha Mapping Project instrument UV ratio values consistent with the presence of water ice and also exhibit annual maximum temperatures below 110 K. However, only ∼3.5% of cold traps exhibit ice exposures. Spectral modeling shows that some ice-bearing pixels may contain ∼30 wt % ice that is intimately mixed with dry regolith. The patchy distribution and low abundance of lunar surface-exposed water ice might be associated with the true polar wander and impact gardening. The observation of spectral features of H2O confirms that water ice is trapped and accumulates in permanently shadowed regions of the Moon, and in some locations, it is exposed at the modern optical surface.}, } @article {pmid30126995, year = {2018}, author = {}, title = {Correction for de Jonge et al., Gene cluster conservation provides insight into cercosporin biosynthesis and extends production to the genus Colletotrichum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8324}, doi = {10.1073/pnas.1812828115}, pmid = {30126995}, issn = {1091-6490}, } @article {pmid30126994, year = {2018}, author = {Crofts, AA and Giovanetti, SM and Rubin, EJ and Poly, FM and Gutiérrez, RL and Talaat, KR and Porter, CK and Riddle, MS and DeNearing, B and Brubaker, J and Maciel, M and Alcala, AN and Chakraborty, S and Prouty, MG and Savarino, SJ and Davies, BW and Trent, MS}, title = {Enterotoxigenic E. coli virulence gene regulation in human infections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8968-E8976}, pmid = {30126994}, issn = {1091-6490}, support = {R01 AI064184/AI/NIAID NIH HHS/United States ; R01 AI076322/AI/NIAID NIH HHS/United States ; R56 AI076322/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Biofilms ; Diarrhea/epidemiology/microbiology/prevention & control ; Enterotoxigenic Escherichia coli/*pathogenicity ; Epithelial Cells/microbiology ; Escherichia coli Infections/epidemiology/immunology/*microbiology/prevention & control ; Escherichia coli Proteins/*genetics/metabolism ; Escherichia coli Vaccines/administration & dosage ; Female ; *Gene Expression Regulation, Bacterial ; Healthy Volunteers ; Host-Pathogen Interactions/*genetics ; Humans ; Intestines/cytology/microbiology ; Iron-Sulfur Proteins/*genetics/metabolism ; Male ; Middle Aged ; Virulence/genetics ; Virulence Factors/genetics/immunology ; Young Adult ; }, abstract = {Enterotoxigenic Escherichia coli (ETEC) is a global diarrheal pathogen that utilizes adhesins and secreted enterotoxins to cause disease in mammalian hosts. Decades of research on virulence factor regulation in ETEC has revealed a variety of environmental factors that influence gene expression, including bile, pH, bicarbonate, osmolarity, and glucose. However, other hallmarks of the intestinal tract, such as low oxygen availability, have not been examined. Further, determining how ETEC integrates these signals in the complex host environment is challenging. To address this, we characterized ETEC's response to the human host using samples from a controlled human infection model. We found ETEC senses environmental oxygen to globally influence virulence factor expression via the oxygen-sensitive transcriptional regulator fumarate and nitrate reduction (FNR) regulator. In vitro anaerobic growth replicates the in vivo virulence factor expression profile, and deletion of fnr in ETEC strain H10407 results in a significant increase in expression of all classical virulence factors, including the colonization factor antigen I (CFA/I) adhesin operon and both heat-stable and heat-labile enterotoxins. These data depict a model of ETEC infection where FNR activity can globally influence virulence gene expression, and therefore proximity to the oxygenated zone bordering intestinal epithelial cells likely influences ETEC virulence gene expression in vivo. Outside of the host, ETEC biofilms are associated with seasonal ETEC epidemics, and we find FNR is a regulator of biofilm production. Together these data suggest FNR-dependent oxygen sensing in ETEC has implications for human infection inside and outside of the host.}, } @article {pmid30126993, year = {2018}, author = {}, title = {Correction for Negrón-Oyarzo et al., Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8577}, doi = {10.1073/pnas.1813107115}, pmid = {30126993}, issn = {1091-6490}, } @article {pmid30126992, year = {2018}, author = {Ferraro, PJ and Sanchirico, JN and Smith, MD}, title = {Causal inference in coupled human and natural systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1805563115}, pmid = {30126992}, issn = {1091-6490}, abstract = {Coupled human and natural systems (CHANS) are complex, dynamic, interconnected systems with feedback across social and environmental dimensions. This feedback leads to formidable challenges for causal inference. Two significant challenges involve assumptions about excludability and the absence of interference. These two assumptions have been largely unexplored in the CHANS literature, but when either is violated, causal inferences from observable data are difficult to interpret. To explore their plausibility, structural knowledge of the system is requisite, as is an explicit recognition that most causal variables in CHANS affect a coupled pairing of environmental and human elements. In a large CHANS literature that evaluates marine protected areas, nearly 200 studies attempt to make causal claims, but few address the excludability assumption. To examine the relevance of interference in CHANS, we develop a stylized simulation of a marine CHANS with shocks that can represent policy interventions, ecological disturbances, and technological disasters. Human and capital mobility in CHANS is both a cause of interference, which biases inferences about causal effects, and a moderator of the causal effects themselves. No perfect solutions exist for satisfying excludability and interference assumptions in CHANS. To elucidate causal relationships in CHANS, multiple approaches will be needed for a given causal question, with the aim of identifying sources of bias in each approach and then triangulating on credible inferences. Within CHANS research, and sustainability science more generally, the path to accumulating an evidence base on causal relationships requires skills and knowledge from many disciplines and effective academic-practitioner collaborations.}, } @article {pmid30126991, year = {2018}, author = {Naveh, GRS and Foster, JE and Silva Santisteban, TM and Yang, X and Olsen, BR}, title = {Nonuniformity in ligaments is a structural strategy for optimizing functionality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {9008-9013}, pmid = {30126991}, issn = {1091-6490}, support = {K99 DE025053/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Mice ; Mice, Transgenic ; Periodontal Ligament/blood supply/*diagnostic imaging/metabolism ; Tooth/blood supply/*diagnostic imaging/metabolism ; *X-Ray Microtomography ; }, abstract = {Ligaments serve as compliant connectors between hard tissues. In that role, they function under various load regimes and directions. The 3D structure of ligaments is considered to form as a uniform entity that changes due to function. The periodontal ligament (PDL) connects the tooth to the bone and sustains different types of loads in various directions. Using the PDL as a model, employing a fabricated motorized setup in a microCT, we demonstrate that the fibrous network structure within the PDL is not uniform, even before the tooth becomes functional. Utilizing morphological automated segmentation methods, directionality analysis, as well as second harmonic generation imaging, we find high correlation between blood vessel distribution and fiber density. We also show a structural feature in a form of a dense collar around the neck of the tooth as well as a preferred direction of the fibrous network. Finally, we show that the PDL develops as a nonuniform structure, with an architecture designed to sustain specific types of load in designated areas. Based on these findings, we propose that ligaments in general should be regarded as nonuniform entities, structured already at developmental stages for optimal functioning under variable load regimes.}, } @article {pmid30126990, year = {2018}, author = {Vonaesch, P and Morien, E and Andrianonimiadana, L and Sanke, H and Mbecko, JR and Huus, KE and Naharimanananirina, T and Gondje, BP and Nigatoloum, SN and Vondo, SS and Kaleb Kandou, JE and Randremanana, R and Rakotondrainipiana, M and Mazel, F and Djorie, SG and Gody, JC and Finlay, BB and Rubbo, PA and Wegener Parfrey, L and Collard, JM and Sansonetti, PJ and , }, title = {Stunted childhood growth is associated with decompartmentalization of the gastrointestinal tract and overgrowth of oropharyngeal taxa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8489-E8498}, pmid = {30126990}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; //CIHR/Canada ; }, mesh = {*Campylobacter/classification/isolation & purification/metabolism ; *Child Development ; Child, Preschool ; *Clostridium/classification/isolation & purification/metabolism ; *Escherichia coli/classification/isolation & purification/metabolism ; Female ; *Gastrointestinal Microbiome ; *Growth Disorders/metabolism/microbiology ; Humans ; *Intestine, Small/metabolism/microbiology ; Male ; *Shigella/classification/isolation & purification/metabolism ; }, abstract = {Linear growth delay (stunting) affects roughly 155 million children under the age of 5 years worldwide. Treatment has been limited by a lack of understanding of the underlying pathophysiological mechanisms. Stunting is most likely associated with changes in the microbial community of the small intestine, a compartment vital for digestion and nutrient absorption. Efforts to better understand the pathophysiology have been hampered by difficulty of access to small intestinal fluids. Here, we describe the microbial community found in the upper gastrointestinal tract of stunted children aged 2-5 y living in sub-Saharan Africa. We studied 46 duodenal and 57 gastric samples from stunted children, as well as 404 fecal samples from stunted and nonstunted children living in Bangui, Central African Republic, and in Antananarivo, Madagascar, using 16S Illumina Amplicon sequencing and semiquantitative culture methods. The vast majority of the stunted children showed small intestinal bacterial overgrowth dominated by bacteria that normally reside in the oropharyngeal cavity. There was an overrepresentation of oral bacteria in fecal samples of stunted children, opening the way for developing noninvasive diagnostic markers. In addition, Escherichia coli/Shigella sp. and Campylobacter sp. were found to be more prevalent in stunted children, while Clostridia, well-known butyrate producers, were reduced. Our data suggest that stunting is associated with a microbiome "decompartmentalization" of the gastrointestinal tract characterized by an increased presence of oropharyngeal bacteria from the stomach to the colon, hence challenging the current view of stunting arising solely as a consequence of small intestine overstimulation through recurrent infections by enteric pathogens.}, } @article {pmid30126989, year = {2018}, author = {}, title = {Correction to Supporting Information for Weinberg et al., Bioinformatic analysis of riboswitch structures uncovers variant classes with altered ligand specificity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8326}, doi = {10.1073/pnas.1811447115}, pmid = {30126989}, issn = {1091-6490}, } @article {pmid30126988, year = {2018}, author = {Dudani, JS and Ibrahim, M and Kirkpatrick, J and Warren, AD and Bhatia, SN}, title = {Classification of prostate cancer using a protease activity nanosensor library.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8954-8959}, pmid = {30126988}, issn = {1091-6490}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Biomarkers, Tumor/biosynthesis/genetics ; *Gene Expression Profiling ; *Gene Library ; Heterografts ; Humans ; Male ; Mice ; Mice, Nude ; Neoplasm Transplantation ; *Neoplasms, Experimental/classification/genetics/metabolism ; *Prostatic Neoplasms/classification/genetics/metabolism ; }, abstract = {Improved biomarkers are needed for prostate cancer, as the current gold standards have poor predictive value. Tests for circulating prostate-specific antigen (PSA) levels are susceptible to various noncancer comorbidities in the prostate and do not provide prognostic information, whereas physical biopsies are invasive, must be performed repeatedly, and only sample a fraction of the prostate. Injectable biosensors may provide a new paradigm for prostate cancer biomarkers by querying the status of the prostate via a noninvasive readout. Proteases are an important class of enzymes that play a role in every hallmark of cancer; their activities could be leveraged as biomarkers. We identified a panel of prostate cancer proteases through transcriptomic and proteomic analysis. Using this panel, we developed a nanosensor library that measures protease activity in vitro using fluorescence and in vivo using urinary readouts. In xenograft mouse models, we applied this nanosensor library to classify aggressive prostate cancer and to select predictive substrates. Last, we coformulated a subset of nanosensors with integrin-targeting ligands to increase sensitivity. These targeted nanosensors robustly classified prostate cancer aggressiveness and outperformed PSA. This activity-based nanosensor library could be useful throughout clinical management of prostate cancer, with both diagnostic and prognostic utility.}, } @article {pmid30126987, year = {2018}, author = {Shehata, HM and Khan, S and Chen, E and Fields, PE and Flavell, RA and Sanjabi, S}, title = {Lack of Sprouty 1 and 2 enhances survival of effector CD8+ T cells and yields more protective memory cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {E8939-E8947}, pmid = {30126987}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; S10 RR028962/RR/NCRR NIH HHS/United States ; DP2 AI112244/AI/NIAID NIH HHS/United States ; P30 AI027763/AI/NIAID NIH HHS/United States ; C06 RR018928/RR/NCRR NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/*immunology ; Adoptive Transfer/methods ; Animals ; CD8-Positive T-Lymphocytes/*physiology/transplantation ; Cell Differentiation/genetics/immunology ; Cell Survival/genetics/immunology ; Diabetes Mellitus, Type 1/blood/immunology/urine ; Disease Models, Animal ; Female ; Humans ; Immunologic Memory/*genetics/immunology ; Intracellular Signaling Peptides and Proteins/genetics/*immunology ; Listeria monocytogenes/immunology/isolation & purification ; Listeriosis/immunology/microbiology/therapy ; Lymphocyte Activation/*genetics/immunology ; Male ; Membrane Proteins/genetics/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phosphoproteins/genetics/*immunology ; Transplantation Chimera ; }, abstract = {Identifying novel pathways that promote robust function and longevity of cytotoxic T cells has promising potential for immunotherapeutic strategies to combat cancer and chronic infections. We show that sprouty 1 and 2 (Spry1/2) molecules regulate the survival and function of memory CD8+ T cells. Spry1/2 double-knockout (DKO) ovalbumin (OVA)-specific CD8+ T cells (OT-I cells) mounted more vigorous autoimmune diabetes than WT OT-I cells when transferred to mice expressing OVA in their pancreatic β-islets. To determine the consequence of Spry1/2 deletion on effector and memory CD8+ T cell development and function, we used systemic infection with lymphocytic choriomeningitis virus (LCMV) Armstrong. Spry1/2 DKO LCMV gp33-specific P14 CD8+ T cells survive contraction better than WT cells and generate significantly more polyfunctional memory T cells. The larger number of Spry1/2 DKO memory T cells displayed enhanced infiltration into infected tissue, demonstrating that absence of Spry1/2 can result in increased recall capacity. Upon adoptive transfer into naive hosts, Spry1/2 DKO memory T cells controlled Listeria monocytogenes infection better than WT cells. The enhanced formation of more functional Spry1/2 DKO memory T cells was associated with significantly reduced mTORC1 activity and glucose uptake. Reduced p-AKT, p-FoxO1/3a, and T-bet expression was also consistent with enhanced survival and memory accrual. Collectively, loss of Spry1/2 enhances the survival of effector CD8+ T cells and results in the formation of more protective memory cells. Deleting Spry1/2 in antigen-specific CD8+ T cells may have therapeutic potential for enhancing the survival and functionality of effector and memory CD8+ T cells in vivo.}, } @article {pmid30126986, year = {2018}, author = {Crowe-McAuliffe, C and Graf, M and Huter, P and Takada, H and Abdelshahid, M and Nováček, J and Murina, V and Atkinson, GC and Hauryliuk, V and Wilson, DN}, title = {Structural basis for antibiotic resistance mediated by the Bacillus subtilis ABCF ATPase VmlR.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8978-8983}, pmid = {30126986}, issn = {1091-6490}, mesh = {ATP-Binding Cassette Transporters/*chemistry/genetics/metabolism ; Allosteric Regulation/drug effects/genetics ; Anti-Bacterial Agents/*chemistry/pharmacology ; Bacillus subtilis/*enzymology/genetics ; Bacterial Proteins/*chemistry/genetics/metabolism ; *Drug Resistance, Bacterial ; RNA, Transfer/chemistry/genetics/metabolism ; Ribosomes/chemistry/genetics/metabolism ; }, abstract = {Many Gram-positive pathogenic bacteria employ ribosomal protection proteins (RPPs) to confer resistance to clinically important antibiotics. In Bacillus subtilis, the RPP VmlR confers resistance to lincomycin (Lnc) and the streptogramin A (SA) antibiotic virginiamycin M (VgM). VmlR is an ATP-binding cassette (ABC) protein of the F type, which, like other antibiotic resistance (ARE) ABCF proteins, is thought to bind to antibiotic-stalled ribosomes and promote dissociation of the drug from its binding site. To investigate the molecular mechanism by which VmlR confers antibiotic resistance, we have determined a cryo-electron microscopy (cryo-EM) structure of an ATPase-deficient B. subtilis VmlR-EQ2 mutant in complex with a B. subtilis ErmDL-stalled ribosomal complex (SRC). The structure reveals that VmlR binds within the E site of the ribosome, with the antibiotic resistance domain (ARD) reaching into the peptidyltransferase center (PTC) of the ribosome and a C-terminal extension (CTE) making contact with the small subunit (SSU). To access the PTC, VmlR induces a conformational change in the P-site tRNA, shifting the acceptor arm out of the PTC and relocating the CCA end of the P-site tRNA toward the A site. Together with microbiological analyses, our study indicates that VmlR allosterically dissociates the drug from its ribosomal binding site and exhibits specificity to dislodge VgM, Lnc, and the pleuromutilin tiamulin (Tia), but not chloramphenicol (Cam), linezolid (Lnz), nor the macrolide erythromycin (Ery).}, } @article {pmid30126985, year = {2018}, author = {Jones, MD and Li, Y and Zamble, DB}, title = {Acid-responsive activity of the Helicobacter pylori metalloregulator NikR.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8966-8971}, pmid = {30126985}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {*Bacterial Proteins/chemistry/genetics/metabolism ; Cytosol/chemistry/metabolism ; Gene Expression Regulation, Bacterial/*physiology ; Gene Expression Regulation, Enzymologic/*physiology ; *Helicobacter pylori/chemistry/genetics/metabolism ; Humans ; Hydrogen-Ion Concentration ; Nickel/metabolism ; *Repressor Proteins/chemistry/genetics/metabolism ; Transcription, Genetic/*physiology ; *Urease/biosynthesis/chemistry/genetics ; }, abstract = {Helicobacter pylori is a human pathogen that infects the stomach, where it experiences variable pH. To survive the acidic gastric conditions, H. pylori produces large quantities of urease, a nickel enzyme that hydrolyzes urea to ammonia, which neutralizes the local environment. One of the regulators of urease expression in H. pylori is HpNikR, a nickel-responsive transcription factor. Here we show that HpNikR also regulates urease expression in response to changes in pH, linking acid adaptation and nickel homeostasis. Upon measuring the cytosolic pH of H. pylori exposed to an external pH of 2, similar to the acidic shock conditions that occur in the human stomach, a significant drop in internal pH was observed. This decrease in internal pH resulted in HpNikR-dependent activation of ureA transcription. Furthermore, analysis of a slate of H. pylori genes encoding other acid adaptation or nickel homeostasis components revealed HpNikR-dependent regulation in response to acid shock. This regulation was consistent with pH-dependent DNA binding to the corresponding promoter sequences observed in vitro with purified HpNikR. These results demonstrate that HpNikR can directly respond to changes in cytosolic pH during acid acclimation and illustrate the exquisitely coordinated regulatory networks that support H. pylori infections in the harsh environment of the human stomach.}, } @article {pmid30126984, year = {2018}, author = {}, title = {Correction for Koehler et al., Transient surface ocean oxygenation recorded in the ∼2.66-Ga Jeerinah Formation, Australia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8323}, doi = {10.1073/pnas.1812988115}, pmid = {30126984}, issn = {1091-6490}, } @article {pmid30126983, year = {2018}, author = {Holden, ZA and Swanson, A and Luce, CH and Jolly, WM and Maneta, M and Oyler, JW and Warren, DA and Parsons, R and Affleck, D}, title = {Decreasing fire season precipitation increased recent western US forest wildfire activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8349-E8357}, pmid = {30126983}, issn = {1091-6490}, mesh = {*Forests ; *Models, Theoretical ; *Rain ; *Seasons ; United States ; *Wildfires ; }, abstract = {Western United States wildfire increases have been generally attributed to warming temperatures, either through effects on winter snowpack or summer evaporation. However, near-surface air temperature and evaporative demand are strongly influenced by moisture availability and these interactions and their role in regulating fire activity have never been fully explored. Here we show that previously unnoted declines in summer precipitation from 1979 to 2016 across 31-45% of the forested areas in the western United States are strongly associated with burned area variations. The number of wetting rain days (WRD; days with precipitation ≥2.54 mm) during the fire season partially regulated the temperature and subsequent vapor pressure deficit (VPD) previously implicated as a primary driver of annual wildfire area burned. We use path analysis to decompose the relative influence of declining snowpack, rising temperatures, and declining precipitation on observed fire activity increases. After accounting for interactions, the net effect of WRD anomalies on wildfire area burned was more than 2.5 times greater than the net effect of VPD, and both the WRD and VPD effects were substantially greater than the influence of winter snowpack. These results suggest that precipitation during the fire season exerts the strongest control on burned area either directly through its wetting effects or indirectly through feedbacks to VPD. If these trends persist, decreases in summer precipitation and the associated summertime aridity increases would lead to more burned area across the western United States with far-reaching ecological and socioeconomic impacts.}, } @article {pmid30126982, year = {2018}, author = {Chuang, YC and Lee, CH and Sun, WH and Chen, CC}, title = {Involvement of advillin in somatosensory neuron subtype-specific axon regeneration and neuropathic pain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8557-E8566}, pmid = {30126982}, issn = {1091-6490}, mesh = {Animals ; Encephalomyelitis, Autoimmune, Experimental/genetics/metabolism ; Focal Adhesions/genetics/metabolism ; Ganglia, Spinal/*physiology ; Growth Cones/*physiology ; Mice ; Mice, Knockout ; Microfilament Proteins/genetics/*metabolism ; Nerve Compression Syndromes/genetics/metabolism ; Neuralgia/genetics/metabolism ; Peripheral Nervous System Diseases/genetics/metabolism ; Pseudopodia/genetics/metabolism ; Regeneration/*physiology ; Sciatic Neuropathy/genetics/metabolism ; }, abstract = {Advillin is a sensory neuron-specific actin-binding protein expressed at high levels in all types of somatosensory neurons in early development. However, the precise role of advillin in adulthood is largely unknown. Here we reveal advillin expression restricted to isolectin B4-positive (IB4+) neurons in the adult dorsal root ganglia (DRG). Advillin knockout (KO) specifically impaired axonal regeneration in adult IB4+ DRG neurons. During axon regeneration, advillin was expressed at the very tips of filopodia and modulated growth cone formation by interacting with and regulating focal-adhesion-related proteins. The advillin-containing focal-adhesion protein complex was shed from neurite tips during neurite retraction and was detectable in cerebrospinal fluid in experimental autoimmune encephalomyelitis, oxaliplatin-induced peripheral neuropathy, and chronic constriction injury of the sciatic nerve. In addition, advillin KO disturbed experimental autoimmune encephalomyelitis-induced neural plasticity in the spinal-cord dorsal horn and aggravated neuropathic pain. Our study highlights a role for advillin in growth cone formation, axon regeneration, and neuropathic pain associated with IB4+ DRG neurons in adulthood.}, } @article {pmid30126981, year = {2018}, author = {Kumagai, NH and García Molinos, J and Yamano, H and Takao, S and Fujii, M and Yamanaka, Y}, title = {Ocean currents and herbivory drive macroalgae-to-coral community shift under climate warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8990-8995}, pmid = {30126981}, issn = {1091-6490}, mesh = {Animals ; Anthozoa/*physiology ; Fishes/*physiology ; *Global Warming ; *Herbivory ; *Oceans and Seas ; Seaweed/*physiology ; }, abstract = {Coral and macroalgal communities are threatened by global stressors. However, recently reported community shifts from temperate macroalgae to tropical corals offer conservation potential for corals at the expense of macroalgae under climate warming. Although such community shifts are expanding geographically, our understanding of the driving processes is still limited. Here, we reconstruct long-term climate-driven range shifts in 45 species of macroalgae, corals, and herbivorous fishes from over 60 years of records (mainly 1950-2015), stretching across 3,000 km of the Japanese archipelago from tropical to subarctic zones. Based on a revised coastal version of climate velocity trajectories, we found that prediction models combining the effects of climate and ocean currents consistently explained observed community shifts significantly better than those relying on climate alone. Corals and herbivorous fishes performed better at exploiting opportunities offered by this interaction. The contrasting range dynamics for these taxa suggest that ocean warming is promoting macroalgal-to-coral shifts both directly by increased competition from the expansion of tropical corals into the contracting temperate macroalgae, and indirectly via deforestation by the expansion of tropical herbivorous fish. Beyond individual species' effects, our results provide evidence on the important role that the interaction between climate warming and external forces conditioning the dispersal of organisms, such as ocean currents, can have in shaping community-level responses, with concomitant changes to ecosystem structure and functioning. Furthermore, we found that community shifts from macroalgae to corals might accelerate with future climate warming, highlighting the complexity of managing these evolving communities under future climate change.}, } @article {pmid30126980, year = {2018}, author = {Liu, L and Doray, B and Kornfeld, S}, title = {Recycling of Golgi glycosyltransferases requires direct binding to coatomer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8984-8989}, pmid = {30126980}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; COP-Coated Vesicles/*enzymology/genetics ; Coat Protein Complex I/genetics/metabolism ; Glucosyltransferases/genetics/*metabolism ; Golgi Apparatus/*enzymology/genetics ; HEK293 Cells ; HeLa Cells ; Humans ; Mucolipidoses/enzymology/genetics ; Mutation, Missense ; Protein Domains ; }, abstract = {The glycosyltransferases of the mammalian Golgi complex must recycle between the stacked cisternae of that organelle to maintain their proper steady-state localization. This trafficking is mediated by COPI-coated vesicles, but how the glycosyltransferases are incorporated into these transport vesicles is poorly understood. Here we show that the N-terminal cytoplasmic tails (N-tails) of a number of cis Golgi glycosyltransferases which share a ϕ-(K/R)-X-L-X-(K/R) sequence bind directly to the δ- and ζ-subunits of COPI. Mutations of this N-tail motif impair binding to the COPI subunits, leading to mislocalization of the transferases to lysosomes. The physiological importance of these interactions is illustrated by mucolipidosis III patients with missense mutations in the N-tail of GlcNAc-1-phosphotransferase that cause the transferase to be rapidly degraded in lysosomes. These studies establish that direct binding of the N-tails of mammalian cis Golgi glycosyltransferases with COPI subunits is essential for recycling within the Golgi.}, } @article {pmid30126703, year = {2018}, author = {Duffy, S and Avery, VM}, title = {Plasmodium falciparum In Vitro Culture - The Highs and Lows.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {812-813}, doi = {10.1016/j.pt.2018.07.010}, pmid = {30126703}, issn = {1471-5007}, mesh = {*Oxygen ; Plasmodium ; *Plasmodium falciparum ; }, } @article {pmid30126619, year = {2018}, author = {Ravignani, A}, title = {Darwin, Sexual Selection, and the Origins of Music.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {10}, pages = {716-719}, doi = {10.1016/j.tree.2018.07.006}, pmid = {30126619}, issn = {1872-8383}, abstract = {Humans devote ample time to produce and perceive music. How and why this behavioral propensity originated in our species is unknown. For centuries, speculation dominated the study of the evolutionary origins of musicality. Following Darwin's early intuitions, recent empirical research is opening a new chapter to tackle this mystery.}, } @article {pmid30126459, year = {2018}, author = {Pyysalo, MJ and Pyysalo, LM and Hiltunen, J and Järnstedt, J and Helminen, M and Karhunen, PJ and Pessi, T}, title = {The dental infections in patients undergoing preoperative dental examination before surgical treatment of saccular intracranial aneurysm.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {600}, pmid = {30126459}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Bacterial Infections/*complications/microbiology ; Dental Plaque/*microbiology ; Escherichia coli/*isolation & purification ; Female ; Finland/epidemiology ; Fusobacterium nucleatum ; Humans ; Intracranial Aneurysm/*microbiology ; Male ; Middle Aged ; Young Adult ; }, abstract = {OBJECTIVE: Dental bacterial DNA and bacterial-driven inflammation markers have previously been detected in intracranial aneurysm tissue samples. This study aimed (i) to assess the possible presence of dental infectious foci, (ii) and the possible association between typical odontogenic bacteria and clinical dental findings in patients undergoing pre-operative dental examination before surgical treatment of saccular intracranial aneurysm. Ninety patients with an intracranial aneurysm were recruited to the study, and the patients' teeth were routinely investigated. Clinical data and bacterial samples from the gingival pockets were collected from a subpopulation of 60 patients. Five typical dental pathogens and total bacteria amounts were measured from gingival samples using real-time quantitative PCR.

RESULTS: The amounts of total bacterial and Fusobacterium nucleatum DNA were significantly higher in the patients with ≥ 6 mm gingival pockets than patients without them (p < 0.01 and p < 0.01, respectively). A total of 43% of patients with an aneurysm had gingival pockets of 6 mm or deeper. Dental infectious foci are fairly common in the Finnish population, with the prevalence of severe periodontitis being around 20%. The frequency of chronic dental infections, especially periodontitis seems to be higher in patients with intracranial aneurysm.}, } @article {pmid30126456, year = {2018}, author = {Milani, C and Casey, E and Lugli, GA and Moore, R and Kaczorowska, J and Feehily, C and Mangifesta, M and Mancabelli, L and Duranti, S and Turroni, F and Bottacini, F and Mahony, J and Cotter, PD and McAuliffe, FM and van Sinderen, D and Ventura, M}, title = {Tracing mother-infant transmission of bacteriophages by means of a novel analytical tool for shotgun metagenomic datasets: METAnnotatorX.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {145}, pmid = {30126456}, issn = {2049-2618}, mesh = {Bacteriophages/*classification/genetics/isolation & purification ; Computational Biology/*methods/standards ; Feces/*virology ; Female ; Gastrointestinal Microbiome ; Genotype ; Humans ; Infant, Newborn ; Male ; Metagenomics/*methods/standards ; Mothers ; Sequence Analysis, DNA/methods ; Software ; }, abstract = {BACKGROUND: Despite the relevance of viral populations, our knowledge of (bacterio) phage populations, i.e., the phageome, suffers from the absence of a "gold standard" protocol for viral DNA extraction with associated in silico sequence processing analyses. To overcome this apparent hiatus, we present here a comprehensive performance evaluation of various protocols and propose an optimized pipeline that covers DNA extraction, sequencing, and bioinformatic analysis of phageome data.

RESULTS: Five widely used protocols for viral DNA extraction from fecal samples were tested for their performance in removal of non-viral DNA. Moreover, we developed a novel bioinformatic platform, METAnnotatorX, for metagenomic dataset analysis. This in silico tool facilitates a range of read- and assembly-based analyses, including taxonomic profiling using an iterative multi-database pipeline, classification of contigs at genus and species level, as well as functional characterizations of reads and assembled data. Performances of METAnnotatorX were assessed through investigation of seven mother-newborn pairs, leading to the identification of shared phage genotypes, of which two were genomically decoded and characterized. METAnnotatorX was furthermore employed to evaluate a protocol for the identification of contaminant non-viral DNA in sequenced datasets and was exploited to determine the amount of metagenomic data needed for robust evaluation of human adult-derived (fecal) phageomes.

CONCLUSIONS: Results obtained in this study demonstrate that a comprehensive pipeline for analysis of phageomes will be pivotal for future explorations of the ecology of phages in the gut environment as well as for understanding their impact on the physiology and bacterial community kinetics as players of dysbiosis and homeostasis in the gut microbiota.}, } @article {pmid30126454, year = {2018}, author = {Taylor, A and Saichua, P and Rhongbutsri, P and Tiengtip, R and Kitvatanachai, S and Taylor, WRJ}, title = {A preliminary epidemiological study of pinworm infection in Thaklong Municipal Early Childhood Development Center and Rangsit Babies' Home, Pathum Thani, Thailand.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {603}, pmid = {30126454}, issn = {1756-0500}, mesh = {Animals ; Child ; Child, Preschool ; Enterobiasis/*epidemiology ; Enterobius/*isolation & purification ; Epidemiologic Studies ; Female ; Humans ; Male ; Prevalence ; Thailand/epidemiology ; }, abstract = {OBJECTIVES: We investigated the prevalence and risk factors for Enterobius vermicularis in children at the Thaklong Municipal Early Childhood Development Center (TMECDC), and the Rangsit Babies' Home (RBH) in Pathum Thani, Thailand using the Scotch tape method.

RESULTS: 397 children aged 3-6 years were sampled (male = 198); 31 (7.8%) were E. vermicularis positive: 1 (TMECDC) and 30 (RBH). 264/397 (66.50%) of parents had incomes > 12,000 baht/month and 313/397 (78.84%) were educated from primary school to college. Univariate analysis identified (i) age 5-6 years, (ii) female sex, (iii) lower education of mother/father, (iv) being a house wife, (v) being a low income family, (vi) being resident in the orphanage, (vii) reporting anorexia and/or fever, and (viii) not washing their bottoms as factors for a positive slide. By logistic regression, education level and age group were independently associated with a positive Scotch tape result. Older children and higher family education had opposing associations with E. vermicularis. Strategies to control pinworm infection should focus on high-risk children in orphanages.}, } @article {pmid30126450, year = {2018}, author = {Solomon, FB and Angore, BN and Koyra, HC and Tufa, EG and Berheto, TM and Admasu, M}, title = {Spectrum of opportunistic infections and associated factors among people living with HIV/AIDS in the era of highly active anti-retroviral treatment in Dawro Zone hospital: a retrospective study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {604}, pmid = {30126450}, issn = {1756-0500}, mesh = {AIDS-Related Opportunistic Infections/*epidemiology ; Adult ; Antiretroviral Therapy, Highly Active ; CD4 Lymphocyte Count ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; HIV Infections/*complications/drug therapy ; Humans ; Male ; Retrospective Studies ; }, abstract = {OBJECTIVES: The study aims to elucidate the spectrum, magnitude and determining factors of the major opportunistic infections in PLHIV patients currently receiving HAART.

RESULTS: A retrospective cross-sectional study was conducted at Tercha Hospital from 744 patient cards. The overall all prevalence of opportunistic infection was 658 (88.4%) developed OIs. Pulmonary tuberculosis, 118 (18%), severe community acquired pneumonia 107 (16.3%) and oral candidiasis 103 (15.6%) were the most common opportunistic infections. Disease stage [AOR = 3.22:95% CI 1.76-5.66], CD4 level [AOR = 2.53:95% CI 1.19-5.37], drug adherence [AOR = 3.02:95% CI 1.57-5.77] and hemoglobin [AOR = 2.49:95% CI 1.34-4.62] showed significant association with OIs. Higher magnitude of opportunistic infection with considerable proportion of AIDS defining illness was detected. So empowerment of skilled man power, health education and provision of antimicrobials is mandatory.}, } @article {pmid30126447, year = {2018}, author = {Feleke, T and Eshetie, S and Dagnew, M and Endris, M and Abebe, W and Tiruneh, M and Moges, F}, title = {Multidrug-resistant bacterial isolates from patients suspected of nosocomial infections at the University of Gondar Comprehensive Specialized Hospital, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {602}, pmid = {30126447}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents ; Child ; *Cross Infection ; *Drug Resistance, Multiple, Bacterial ; Escherichia coli/drug effects/*isolation & purification ; Escherichia coli Infections/*drug therapy/epidemiology ; Ethiopia/epidemiology ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Staphylococcal Infections/*drug therapy/epidemiology ; Staphylococcus aureus/drug effects/*isolation & purification ; Young Adult ; }, abstract = {OBJECTIVES: As the hospital environment favors the circulation of drug resistant bacteria, continuous surveillance of antibiotic resistant patterns is an important approach for a better patient management. This study is therefore, aimed to assess multidrug resistant bacterial isolates from patients suspected of nosocomial infections at the University of Gondar Comprehensive Specialized Hospital, Gondar, Ethiopia.

RESULTS: Of the 260 patients, 173 (66.5%) of them were culture positive. Among culture positive patients a total of 216 bacterial isolates were recovered, of which the most common species were S. aureus 77 (35.6%), followed by E. coli 33 (15.3%) and Klebsiella spp 29 (13.4%). Of the S. aureus isolates, 67.5% were cefoxitin (methicillin) resistant. Citrobacter spp (100%), Klebsiella spp (79.3%) and E. coli (75.3%) were the leading MDR Gram-negative isolates. The overall MDR resistant rate was 152 (70.4%).}, } @article {pmid30126446, year = {2018}, author = {Weldesamuel, GT and Atalay, HT and Zemichael, TM and Gebre, HG and Abraha, DG and Amare, AK and Gidey, EB and Alemayoh, TT}, title = {Colostrum avoidance and associated factors among mothers having children less than 2 years of age in Aksum town, Tigray, Ethiopia: a cross-sectional study 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {601}, pmid = {30126446}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; *Breast Feeding ; Child, Preschool ; *Colostrum ; Cross-Sectional Studies ; Ethiopia ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Mothers ; Pregnancy ; *Prenatal Care ; Young Adult ; }, abstract = {OBJECTIVE: To assess colostrum avoidance practices and associated factors among mothers of children aged less than two in Aksum town, Tigray, Ethiopia, 2017.

RESULT: Colostrum avoidance was practiced by 6.3% (95% CI = 4.2%, 8.6%) of mothers having children aged < 24 months in Aksum town. In a multivariate logistic regression analysis at P value of < 0.05, lower number of antenatal care visit (AOR = 4.45, 95% CI = 1.9, 10.5), lack postnatal follow up [AOR = 2.98 (95% CI = 1.22, 7)] and poor maternal level of information on colostrum feeding [AOR = 4.8 (95% CI = 1.83, 12.69)] were statistically associated with colostrum avoidance. Coordination, strengthening and sustaining of awareness creation strategies and approaches is recommended for the promotion of the nutritional value of colostrum and its health benefits.}, } @article {pmid30126442, year = {2018}, author = {Nganou-Gnindjio, CN and Mba, CM and Azabji-Kenfack, M and Dehayem, MY and Mfeukeu-Kuate, L and Mbanya, JC and Sobngwi, E}, title = {Poor glycemic control impacts heart rate variability in patients with type 2 diabetes mellitus: a cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {599}, pmid = {30126442}, issn = {1756-0500}, mesh = {Cross-Sectional Studies ; Diabetes Mellitus, Type 2/*complications ; Electrocardiography, Ambulatory ; *Heart Rate ; Humans ; *Hyperglycemia ; Male ; Middle Aged ; }, abstract = {OBJECTIVE: We aimed to determine and compare HRV parameters in poorly and well controlled type 2 diabetes. 54 normotensive type 2 diabetes patients without clinical signs of CAN were enrolled; 29 poorly controlled (HbA1c ≥ 7%) and 25 controls matched for age, sex and BMI. HRV analysis was performed using 24-h ambulatory ECG, with automatic estimation of the time and frequency domain ranges. Comparisons were performed using Mann-Whitney test.

RESULTS: We included 54 participants (26 males) aged 56 years [43-62], with known duration of diabetes 3 years [1-7]. HbA1c was 10.1% [9.1-11.9] vs 5.3% [5.1-6.3] (p < 0.001). Blood pressure was 126 mmHg [121-130] vs 124 mmHg [113-133] in the poorly controlled group and the well-controlled group respectively (p = 0.5). 24-h mean heart rate was significantly higher in poorly controlled vs well controlled patients (79 bpm [77-83] vs 75 bpm [69-79], p = 0.006). In the time domain analysis, markers of the overall variability were lower and thus altered in the poorly controlled group (SDNN: 102 ms [90.5-111.1] vs 112.3 ms [104.4-131.2], p = 0.01 and SDANN 88 ms [72.9-99.7] vs 97.8 ms [91.8-114.5], p = 0.01). The frequency domain analysis showed trends towards lower values of sympathovagal balance markers in the poorly controlled group. Reduced HRV is associated with poorly controlled type 2 diabetes mellitus and may be an early marker in clinical practice.}, } @article {pmid30126372, year = {2018}, author = {Bachas, C and Hodzic, J and van der Mijn, JC and Stoepker, C and Verheul, HMW and Wolthuis, RMF and Felley-Bosco, E and van Wieringen, WN and van Beusechem, VW and Brakenhoff, RH and de Menezes, RX}, title = {Rscreenorm: normalization of CRISPR and siRNA screen data for more reproducible hit selection.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {301}, pmid = {30126372}, issn = {1471-2105}, support = {CCA2014-5-19//Stichting VUmc Cancer Center Amsterdam/ ; 10701//KWF Kankerbestrijding/ ; }, mesh = {Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; Genetic Testing/*methods ; Genomics/*methods ; Humans ; RNA, Small Interfering/*genetics ; Reproducibility of Results ; }, abstract = {BACKGROUND: Reproducibility of hits from independent CRISPR or siRNA screens is poor. This is partly due to data normalization primarily addressing technical variability within independent screens, and not the technical differences between them.

RESULTS: We present "rscreenorm", a method that standardizes the functional data ranges between screens using assay controls, and subsequently performs a piecewise-linear normalization to make data distributions across all screens comparable. In simulation studies, rscreenorm reduces false positives. Using two multiple-cell lines siRNA screens, rscreenorm increased reproducibility between 27 and 62% for hits, and up to 5-fold for non-hits. Using publicly available CRISPR-Cas screen data, application of commonly used median centering yields merely 34% of overlapping hits, in contrast with rscreenorm yielding 84% of overlapping hits. Furthermore, rscreenorm yielded at most 8% discordant results, whilst median-centering yielded as much as 55%.

CONCLUSIONS: Rscreenorm yields more consistent results and keeps false positive rates under control, improving reproducibility of genetic screens data analysis from multiple cell lines.}, } @article {pmid30126371, year = {2018}, author = {Liu, X and Cao, X and Shi, S and Zhao, N and Li, D and Fang, P and Chen, X and Qi, W and Zhang, Z}, title = {Comparative RNA-Seq analysis reveals a critical role for brassinosteroids in rose (Rosa hybrida) petal defense against Botrytis cinerea infection.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {62}, pmid = {30126371}, issn = {1471-2156}, support = {31772344//National Natural Science Foundation of China/ ; 31501791//National Natural Science Foundation of China/ ; 6162017//Natural Science Foundation of Beijing Municipality/ ; }, abstract = {BACKGROUND: One of the most popular ornamental plants worldwide, roses (Rosa sp.), are very susceptible to Botrytis gray mold disease. The necrotrophic infection of rose petals by B. cinerea causes the collapse and death of these tissues in both the growth and post-harvest stages, resulting in serious economic losses. To understand the molecular basis of rose resistance against B. cinerea, we profiled the petal transcriptome using RNA-Seq technology.

RESULTS: We identified differentially transcribed genes (DTGs) in petals during B. cinerea infection at 30 h post inoculation (hpi) and/or 48 hpi. Gene ontology term enrichment and pathway analyses revealed that metabolic, secondary metabolite biosynthesis, plant-pathogen interaction, and plant hormone signal transduction pathways were involved. The expression of 370 cell-surface immune receptors was upregulated during infection. In addition, 188 genes encoding transcription factors were upregulated, particularly in the ERF, WRKY, bHLH, MYB, and NAC families, implying their involvement in resistance against B. cinerea. We further identified 325 upregulated DTGs in the hormone signal transduction pathways. Among them, the brassinosteroid (BR)-related genes were the most significantly enriched. To confirm the role of BR in Botrytis resistance, exogenous BR was applied to rose flowers before the inoculation of B. cinerea, which enhanced the defense response in these petals.

CONCLUSIONS: Our global transcriptome profiling provides insights into the complex gene regulatory networks mediating the rose petal response to B. cinerea. We further demonstrated the role of the phytohormone BR in the resistance of petals to necrotrophic fungal pathogens.}, } @article {pmid30126368, year = {2018}, author = {Kang, N and Wang, Y and Guo, S and Ou, Y and Wang, G and Chen, J and Li, D and Zhan, Q}, title = {Mutant TP53 G245C and R273H promote cellular malignancy in esophageal squamous cell carcinoma.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {16}, pmid = {30126368}, issn = {1471-2121}, support = {2015CB553904//National 973 Program/International ; 81321091, 81230047//National Natural Science Foundation of China/International ; 2013BAI01B07//National Sci-Tech Support Plan/International ; xx2018040//Beijing Nova Program/International ; 81672455//national nature science/International ; 2017-I2M-3-004//CAMS Initiative for Innovative Medicine/International ; }, mesh = {Apoptosis/genetics ; Cell Cycle Checkpoints/genetics ; Cell Line, Tumor ; Cell Movement/genetics ; Cell Proliferation/genetics ; Cell Transformation, Neoplastic/*genetics/*pathology ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; DNA Mutational Analysis ; Esophageal Squamous Cell Carcinoma/*genetics/*pathology ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism ; Mutation/*genetics ; Neoplasm Invasiveness ; Poly(ADP-ribose) Polymerases/metabolism ; Tumor Suppressor Protein p53/*genetics ; }, abstract = {BACKGROUND: TP53 gene mutations occur in more than 50% of human cancers and the vast majority of these mutations in human cancers are missense mutations, which broadly occur in DNA binding domain (DBD) (Amino acids 102-292) and mainly reside in six "hotspot" residues. TP53 G245C and R273H point mutations are two of the most frequent mutations in tumors and have been verified in several different cancers. In the previous study of the whole genome sequencing (WGS), we found some mutations of TP53 DBD in esophageal squamous cell carcinoma (ESCC) clinical samples. We focused on two high-frequent mutations TP53 p.G245C and TP53 p.R273H and investigated their oncogenic roles in ESCC cell lines, p53-defective cell lines H1299 and HCT116 p53-/-.

RESULTS: MTS and colony formation assays showed that mutant TP53 G245C and R273H increased cell vitality and proliferation. Flow cytometry results revealed inhibition of ultraviolet radiation (UV)- and ionizing radiation (IR)- induced apoptosis and disruption of TP53-mediated cell cycle arrest after UV, IR and Nocodazole treatment. Transwell assays indicated that mutant TP53 G245C and R273H enhanced cell migration and invasion abilities. Moreover, western blot revealed that they were able to suppress the expression of TP53 downstream genes in the process of apoptosis and cell cycle arrest induced by UV, which suggests that these two mutations can influence apoptosis and growth arrest might be due, at least in part, to down-regulate the expression of P21, GADD45α and PARP.

CONCLUSIONS: These results indicate that mutant TP53 G245C and R273H can lead to more aggressive phenotypes and enhance cancer cell malignancy, which further uncover TP53 function in carcinogenesis and might be useful in clinical diagnosis and therapy of TP53 mutant cancers.}, } @article {pmid30126366, year = {2018}, author = {Argemi, X and Matelska, D and Ginalski, K and Riegel, P and Hansmann, Y and Bloom, J and Pestel-Caron, M and Dahyot, S and Lebeurre, J and Prévost, G}, title = {Comparative genomic analysis of Staphylococcus lugdunensis shows a closed pan-genome and multiple barriers to horizontal gene transfer.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {621}, pmid = {30126366}, issn = {1471-2164}, support = {2014/15/B/NZ1/03357//Polish National Science Centre/ ; }, mesh = {CRISPR-Cas Systems/genetics ; Gene Transfer, Horizontal/*genetics ; *Genome, Bacterial ; Humans ; Phylogeny ; Sequence Analysis, DNA ; Staphylococcal Infections/microbiology ; Staphylococcus lugdunensis/*genetics ; Virulence ; Virulence Factors/genetics ; }, abstract = {BACKGROUND: Coagulase negative staphylococci (CoNS) are commensal bacteria on human skin. Staphylococcus lugdunensis is a unique CoNS which produces various virulence factors and may, like S. aureus, cause severe infections, particularly in hospital settings. Unlike other staphylococci, it remains highly susceptible to antimicrobials, and genome-based phylogenetic studies have evidenced a highly conserved genome that distinguishes it from all other staphylococci.

RESULTS: We demonstrate that S. lugdunensis possesses a closed pan-genome with a very limited number of new genes, in contrast to other staphylococci that have an open pan-genome. Whole-genome nucleotide and amino acid identity levels are also higher than in other staphylococci. We identified numerous genetic barriers to horizontal gene transfer that might explain this result. The S. lugdunensis genome has multiple operons encoding for restriction-modification, CRISPR/Cas and toxin/antitoxin systems. We also identified a new PIN-like domain-associated protein that might belong to a larger operon, comprising a metalloprotease, that could function as a new toxin/antitoxin or detoxification system.

CONCLUSION: We show that S. lugdunensis has a unique genome profile within staphylococci, with a closed pan-genome and several systems to prevent horizontal gene transfer. Its virulence in clinical settings does not rely on its ability to acquire and exchange antibiotic resistance genes or other virulence factors as shown for other staphylococci.}, } @article {pmid30126365, year = {2018}, author = {Orfanos, S and Gomez, C and Baron, S and Akkisetty, R and Dufeu, N and Coltey, B and Thomas, PA and Rolain, JM and Reynaud-Gaubert, M}, title = {Impact of gram negative bacteria airway recolonization on the occurrence of chronic lung allograft dysfunction after lung transplantation in a population of cystic fibrosis patients.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {88}, pmid = {30126365}, issn = {1471-2180}, abstract = {BACKGROUND: Chronic Lung Allograft Dysfunction (CLAD) is the main cause of morbidity and mortality after the first year following lung transplantation (LTx). Risk factors of CLAD have been extensively studied, but the association between gram-negative bacteria (GNB) bronchial colonization and the development of CLAD is controversial. The purpose of our study was to investigate the association between post-transplant recolonization with the same species or de-novo colonization with a new GNB species and CLAD. The same analysis was performed on a sub-group of patients at the strain level using Matrix Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry technique.

RESULTS: Forty adult cystic fibrosis (CF) patients who underwent a first bilateral LTx in the University Hospital of Marseille, between January 2010 and December 2014, were included in the study. Patients with GNB de-novo colonization had a higher risk of developing CLAD (OR = 6.72, p = 0.04) and a lower rate of CLAD-free survival (p = 0.005) compared to patients with GNB recolonization. No conclusion could be drawn from the subgroup MALDI-TOF MS analysis at the strain level.

CONCLUSION: Post-LTx GNB airway recolonization seems to be a protective factor against CLAD, whereas de-novo colonization with a new species of GNB seems to be a risk factor for CLAD.}, } @article {pmid30126363, year = {2018}, author = {Fan, S and Wang, J and Lei, C and Gao, C and Yang, Y and Li, Y and An, N and Zhang, D and Han, M}, title = {Identification and characterization of histone modification gene family reveal their critical responses to flower induction in apple.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {173}, pmid = {30126363}, issn = {1471-2229}, support = {CARS-27//China Apple Research System/ ; 31672101//National Natural Science Foundation of China/ ; 2017ZDXM-NY-019//Shaanxi key research and development plan/ ; }, mesh = {Flowers/genetics/growth & development/metabolism ; Genes, Plant/*genetics ; Histone Code ; Malus/*genetics/growth & development/metabolism ; *Multigene Family ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Histone methylation and acetylation regulate biological processes in plants through various histone modifications (HMs) gene families. However, knowledge of HMs genes is limited in horticultural deciduous trees, including apple (Malus domestica).

RESULTS: Here, a comprehensive study of identifying and investigating HMs genes was performed using the recently published apple genome. In total, 198 MdHMs were identified, including 71 histone methyltransferases, 44 histone demethylases, 57 histone acetylases, and 26 histone deacetylases. Detailed analysis of the MdHMs, including chromosomes locations, gene structures, protein motif and protein-protein interactions were performed, and their orthologous genes were also predicted against nine plant species. Meanwhile, a syntenic analysis revealed that tandem, segmental, and whole genome duplications were involved in the evolution and expansion of the MdHMs gene family. Most MdHMs underwent purifying selection. The expression profiles of 198 MdHMs were investigated in response to 6-BA treatment and different flowering varieties (easy-flowering 'Yanfu No.6' and difficult-flowering 'Nagafu No.2') using transcriptome sequencing data, and most MdHMs were involved in flower induction processes. Subsequent quantitative real-time PCR was then performed to confirm the expression levels of candidate MdHMs under different flowering-related circumstances.

CONCLUSION: MdHMs were involved in, and responsive to, flower induction in apple. This study established an MdHMs platform that provided valuable information and presented enriched biological theories on flower induction in apple. The data could also be used to study the evolutionary history and functional prospects of MdHMs genes, as well as other trees.}, } @article {pmid30126356, year = {2018}, author = {Francis, F and Dumas, MD and Davis, SB and Wisser, RJ}, title = {Clustering of circular consensus sequences: accurate error correction and assembly of single molecule real-time reads from multiplexed amplicon libraries.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {302}, pmid = {30126356}, issn = {1471-2105}, support = {P20 GM103446/GM/NIGMS NIH HHS/United States ; 1127076//Division of Integrative Organismal Systems/ ; }, mesh = {Genetic Testing/*methods ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Targeted resequencing with high-throughput sequencing (HTS) platforms can be used to efficiently interrogate the genomes of large numbers of individuals. A critical issue for research and applications using HTS data, especially from long-read platforms, is error in base calling arising from technological limits and bioinformatic algorithms. We found that the community standard long amplicon analysis (LAA) module from Pacific Biosciences is prone to substantial bioinformatic errors that raise concerns about findings based on this pipeline, prompting the need for a new method.

RESULTS: A single molecule real-time (SMRT) sequencing-error correction and assembly pipeline, C3S-LAA, was developed for libraries of pooled amplicons. By uniquely leveraging the structure of SMRT sequence data (comprised of multiple low quality subreads from which higher quality circular consensus sequences are formed) to cluster raw reads, C3S-LAA produced accurate consensus sequences and assemblies of overlapping amplicons from single sample and multiplexed libraries. In contrast, despite read depths in excess of 100X per amplicon, the standard long amplicon analysis module from Pacific Biosciences generated unexpected numbers of amplicon sequences with substantial inaccuracies in the consensus sequences. A bootstrap analysis showed that the C3S-LAA pipeline per se was effective at removing bioinformatic sources of error, but in rare cases a read depth of nearly 400X was not sufficient to overcome minor but systematic errors inherent to amplification or sequencing.

CONCLUSIONS: C3S-LAA uses a divide and conquer processing algorithm for SMRT amplicon-sequence data that generates accurate consensus sequences and local sequence assemblies. Solving the confounding bioinformatic source of error in LAA allowed for the identification of limited instances of errors due to DNA amplification or sequencing of homopolymeric nucleotide tracts. For research and development in genomics, C3S-LAA allows meaningful conclusions and biological inferences to be made from accurately polished sequence output.}, } @article {pmid30126076, year = {2018}, author = {Hidalgo-Ahumada, CAP and Nobu, MK and Narihiro, T and Tamaki, H and Liu, WT and Kamagata, Y and Stams, AJM and Imachi, H and Sousa, DZ}, title = {Novel energy conservation strategies and behaviour of Pelotomaculum schinkii driving syntrophic propionate catabolism.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4503-4511}, doi = {10.1111/1462-2920.14388}, pmid = {30126076}, issn = {1462-2920}, support = {024.002.002//Gravitation Grant/ ; 323009//ERC Grant/ ; }, abstract = {Under methanogenic conditions, short-chain fatty acids are common byproducts from degradation of organic compounds and conversion of these acids is an important component of the global carbon cycle. Due to the thermodynamic difficulty of propionate degradation, this process requires syntrophic interaction between a bacterium and partner methanogen; however, the metabolic strategies and behaviour involved are not fully understood. In this study, the first genome analysis of obligately syntrophic propionate degraders (Pelotomaculum schinkii HH and P. propionicicum MGP) and comparison with other syntrophic propionate degrader genomes elucidated novel components of energy metabolism behind Pelotomaculum propionate oxidation. Combined with transcriptomic examination of P. schinkii behaviour in co-culture with Methanospirillum hungatei, we found that formate may be the preferred electron carrier for P. schinkii syntrophy. Propionate-derived menaquinol may be primarily re-oxidized to formate, and energy was conserved during formate generation through newly proposed proton-pumping formate extrusion. P. schinkii did not overexpress conventional energy metabolism associated with a model syntrophic propionate degrader Syntrophobacter fumaroxidans MPOB (i.e., CoA transferase, Fix and Rnf). We also found that P. schinkii and the partner methanogen may also interact through flagellar contact and amino acid and fructose exchange. These findings provide new understanding of syntrophic energy acquisition and interactions.}, } @article {pmid30126070, year = {2018}, author = {De Paepe, K and Verspreet, J and Verbeke, K and Raes, J and Courtin, CM and Van de Wiele, T}, title = {Introducing insoluble wheat bran as a gut microbiota niche in an in vitro dynamic gut model stimulates propionate and butyrate production and induces colon region specific shifts in the luminal and mucosal microbial community.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3406-3426}, doi = {10.1111/1462-2920.14381}, pmid = {30126070}, issn = {1462-2920}, support = {IWT130028//Fonds Wetenschappelijk Onderzoek/ ; }, abstract = {The spatial organization of gut microorganisms is important with respect to their functional role in the gut ecosystem. Regional differences in the longitudinal and lateral direction are, however, not frequently studied, given the difficulty to sample these human gut regions in vivo. Particularly the insoluble food particle-associated microbiota is poorly studied. Therefore, the long-term effects of insoluble wheat bran supplementation on the composition and functionality of the gut microbial community derived from six individuals were explored in the Dietary Particle-Mucosal-Simulator of the Human Intestinal Microbial Ecosystem in vitro model. Wheat bran stimulated propionate and butyrate production and induced shifts in the luminal and mucosal microbial community composition. The insoluble wheat bran residue and the mucus layer were identified as crucial platforms in sustaining diversity by selectively enriching species, which are not thriving in the luminal environment, including Lactobacillus, Bifidobacterium and Dialister species, Roseburia faecis, Prevotella copri and Bacteroides ovatus. Despite the evident habitat preference, some parallels could be drawn between the enrichment of taxa on bran platforms and their stimulation in the luminal and mucosal communities. Removing wheat bran during the wash-out period reversed the functional effects and gave rise to a blooming of some taxa that are considered opportunistic pathogens.}, } @article {pmid30126050, year = {2018}, author = {Cantos, R and Labella, JI and Espinosa, J and Contreras, A}, title = {The nitrogen regulator PipX acts in cis to prevent operon polarity.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12688}, pmid = {30126050}, issn = {1758-2229}, support = {BFU2012-33364BFU2015-66360-P//Ministerio de Economía y Competitividad/ ; FPUUA59//University of Alicante/ ; }, abstract = {Cyanobacteria, phototrophic organisms performing oxygenic photosynthesis, must adapt their metabolic processes to important environmental challenges, like those imposed by the succession of days and nights. Not surprisingly, certain regulatory proteins are found exclusively in this phylum. One of these unique factors, PipX, provides a mechanistic link between signals of carbon/nitrogen and of energy, transduced by the signalling protein PII, and the control of gene expression by the global nitrogen regulator NtcA. Here we report a new regulatory function of PipX: enhancement in cis of pipY expression, a gene encoding a universally conserved protein involved in amino/keto acid and Pyridoxal phosphate homeostasis. In Synechococcus elongatus and many other cyanobacteria these genes are expressed as a bicistronic pipXY operon. Despite being cis-acting, polarity suppression by PipX is nevertheless reminiscent of the function of NusG paralogues typified by RfaH, which are non-essential operon-specific bacterial factors acting in trans to upregulate horizontally-acquired genes. Furthermore, PipX and members of the NusG superfamily share a TLD/KOW structural domain, suggesting regulatory interactions of PipX with the translation machinery. Our results also suggest that the cis-acting function of PipX is a sophisticated regulatory strategy for maintaining appropriate PipX-PipY stoichiometry.}, } @article {pmid30126031, year = {2018}, author = {Cao, H and Huang, P and Yan, Y and Shi, Y and Dong, B and Liu, X and Ye, L and Lin, F and Lu, J}, title = {The basic helix-loop-helix transcription factor Crf1 is required for development and pathogenicity of the rice blast fungus by regulating carbohydrate and lipid metabolism.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3427-3441}, doi = {10.1111/1462-2920.14387}, pmid = {30126031}, issn = {1462-2920}, support = {2014CB541702//National Basic Research Program of China/ ; 31371891//National Natural Science Foundation of China/ ; 31671975//National Natural Science Foundation of China/ ; }, abstract = {Pyricularia oryzae is a plant pathogen causing rice blast, a serious disease spreading in cultivated rice globally. Transcription factors play important regulatory roles in fungal development and pathogenicity. Here, we characterized the biological functions of Crf1, a basic helix-loop-helix (bHLH) transcription factor, in the development and pathogenicity of P. oryzae with functional genetics, molecular and biochemical approaches. We found that CRF1 is necessary for virulence and plays an indispensable role in the regulation of carbohydrate and lipid metabolism in P. oryzae. Deletion of CRF1 led to defects in utilization of lipids, ethanol, glycerol and L-arabinose, and down-regulation of many important genes in lipolysis, β-oxidation, gluconeogenesis, as well as glycerol and arabinose metabolism. CRF1 is also essential for peroxisome and vacuole function, and conidial cell death during appressorium formation. The appressorium turgor, penetration ability and virulence in Δcrf1 were restored by supplementation of exogenous glucose. The virulence of Crf1 mutant was also recovered by adding exogenous D-xylose, but not by addition of ethanol, pyruvate, leucine or L-arabinose. These data showed that Crf1 plays an important role in the complex regulatory network of carbohydrate and lipid metabolism that governs fungal development and pathogenicity.}, } @article {pmid30125655, year = {2018}, author = {Chu, H and Jo, Y and Choi, H and Lee, BC and Cho, WK}, title = {Identification of viral domains integrated into Arabidopsis proteome.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {246-257}, doi = {10.1016/j.ympev.2018.08.009}, pmid = {30125655}, issn = {1095-9513}, abstract = {Horizontal gene transfer (HGT) contributes to the genome evolution of living organisms. In particular, several recent studies provide convincing data on the integration of viral sequences into diverse organisms. Here, we identified 101 viral domains integrated into the model plant Arabidopsis proteome. Functional analysis based on gene ontology (GO) terms indicates that viral domains in the Arabidopsis proteome were involved in various stress responses with binding functions. Protein interaction networks support the strong protein interactions of viral domains with other Arabidopsis proteins. A proteome-wide analysis gave a comprehensive evolutionary view of viral domains integrated into 41 plant proteomes, revealing the specific and conserved integration of viral domains into plant proteomes. Phylogenetic analyses revealed the possible HGT between viral domains and plant proteomes. Our results provide an overview of the integration of viral domains into plant proteomes and their possible functional roles associated with plant defense mechanisms.}, } @article {pmid30125437, year = {2018}, author = {Parchman, TL and Edelaar, P and Uckele, K and Mezquida, ET and Alonso, D and Jahner, JP and Summers, RW and Benkman, CW}, title = {Resource stability and geographic isolation are associated with genome divergence in western Palearctic crossbills.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1715-1731}, doi = {10.1111/jeb.13367}, pmid = {30125437}, issn = {1420-9101}, abstract = {While many conifers produce annually variable seed crops, serotinous species (which hold seeds in cones for multiple years) represent unusually stable food resources for seed predators. Such stability is conducive to residency and potentially population divergence of consumers as exemplified by the Cassia crossbill (Loxia sinesciuris) in North America. We used genotyping by sequencing (GBS) to test whether three Mediterranean subspecies of common crossbills (L. curvirostra) associated with the serotinous Aleppo pine (Pinus halepensis) were more genetically distinct than European crossbills associated with nonserotinous conifers. We assembled a Cassia crossbill draft genome as a reference for mapping GBS reads and as a first step towards a more contiguous genome assembly. We found clear patterns of genetic divergence for each of the P. halepensis-associated subspecies. Geographic isolation, as promoted by resource stability and residency, is associated with genetic divergence of two of these subspecies. However, geographic isolation cannot account for divergence of L. c. hispana. Instead, resource stability likely contributed to divergence by reducing dispersal and increasing resource competition that may limit breeding by immigrants. In contrast, we found no differentiation among common crossbills associated with less stable resources, and only slight differentiation between common crossbills and parrot crossbills (L. pytyopsittacus). The substantial morphological divergence between common and parrot crossbills has likely originated or been maintained by selection despite gene flow generated by spatiotemporal resource fluctuation. Our results indicate that phenological as well as morphological characteristics of conifers have influenced crossbill diversification, and suggest a possible link between resource stability and population divergence.}, } @article {pmid30125237, year = {2018}, author = {Koffel, T and Daufresne, T and Massol, F and Klausmeier, CA}, title = {Plant Strategies along Resource Gradients.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {360-378}, doi = {10.1086/698600}, pmid = {30125237}, issn = {1537-5323}, abstract = {Plants present a variety of defensive strategies against herbivores, broadly classified into tolerance and resistance. Since resource availability can also limit plant growth, we expect plant allocation to resource acquisition and defense to vary along resource gradients. Yet, the conditions under which one defensive strategy is favored over the other are unclear. Here, we use an eco-evolutionary model to investigate plant adaptive allocation to resource acquisition, tolerance, and resistance along a resource gradient in a simple food web module inspired by plankton communities where plants compete for a single resource and are grazed on by a shared herbivore. We show that undefended, acquisition-specialist strategies dominate under low resource supplies. Conversely, high resource supplies, which lead to high herbivore abundance because of trophic transfers, result in either the dominance of very resistant strategies or coexistence between a completely resistant strategy and a fast-growing, tolerant one. We also explore the consequences of this adaptive allocation on species biomasses. Finally, we compare our predictions to a more traditional, density-independent optimization model. We show that density dependence mediated by resources and herbivores is the cause of the increase in plant resistance along the resource gradient, as the optimization model would instead have favored tolerance.}, } @article {pmid30125236, year = {2018}, author = {Rhoades, OK and Best, RJ and Stachowicz, JJ}, title = {Assessing Feeding Preferences of a Consumer Guild: Partitioning Variation Among versus Within Species.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {287-300}, doi = {10.1086/698325}, pmid = {30125236}, issn = {1537-5323}, abstract = {Interspecific variation in resource use is critical to understanding species diversity, coexistence, and ecosystem functioning. A growing body of research describes analogous intraspecific variation and its potential importance for population dynamics and community outcomes. However, the magnitude of intraspecific variation relative to interspecific variation in key dimensions of consumer-resource interactions remains unknown, hampering our understanding of the importance of this variation for population and community processes. In this study, we examine feeding preference through repeated laboratory choice feeding assays of 444 wild-caught individuals of eight invertebrate grazer species on rocky reefs in northern California. Between-species variation accounted for 25%-33% of the total variation in preference for the preferred resource, while between-individual variation accounted for 4%-5% of total variation. For two of the eight species, between-individual variation was significantly different from zero and on average contributed 14% and 17% of the total diet variation, even after accounting for differences due to size and sex. Therefore, even with clearly distinguishable between-species differences in mean preference, diet variation between and within individuals can contribute to the dietary niche width of species and guilds, which may be overlooked by focusing solely on species' mean resource use patterns.}, } @article {pmid30125235, year = {2018}, author = {Baudier, KM and D'Amelio, CL and Malhotra, R and O'Connor, MP and O'Donnell, S}, title = {Extreme Insolation: Climatic Variation Shapes the Evolution of Thermal Tolerance at Multiple Scales.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {347-359}, doi = {10.1086/698656}, pmid = {30125235}, issn = {1537-5323}, abstract = {The climatic variability hypothesis (CVH) is a cornerstone of thermal ecology, predicting the evolution of wider organismal thermal tolerance ranges in more thermally variable environments. Thermal tolerance ranges depend on both upper and lower tolerance limits (critical thermal maxima [[Formula: see text]] and critical thermal minima [[Formula: see text]]), which may show different responses to environmental gradients. To delineate the relative effects of mean and extreme temperatures on thermal tolerances, we conducted a within-latitude comparative test of CVH predictions for army ants (Dorylinae) at multiple scales: across elevations, in seasonal versus aseasonal forests, and in subterranean versus surface microhabitats. Consistent with the CVH, thermally buffered subterranean species had narrower thermal tolerance ranges. Both [Formula: see text] and [Formula: see text] decreased with elevation for subterranean species. In contrast, aboveground species (those exposed to insolation) showed a decrease in [Formula: see text] but no change in [Formula: see text] across elevations. Furthermore, greater seasonal temperature variation in dry forests correlated with increased [Formula: see text] but not [Formula: see text]. These patterns suggest that [Formula: see text] and [Formula: see text] respond to different abiotic selective forces: habitat-specific exposure to extreme insolation corresponds to [Formula: see text] differences but not to [Formula: see text] variation. We predict that increasingly frequent heat spikes associated with climate change will have habitat-specific physiological consequences for ectothermic animals. Models predicting climate change impacts should account for species microhabitat uses and within-latitude differences in temperature seasonality.}, } @article {pmid30125234, year = {2018}, author = {Waananen, A and Kiefer, G and Ison, JL and Wagenius, S}, title = {Mating Opportunity Increases with Synchrony of Flowering among Years More than Synchrony within Years in a Nonmasting Perennial.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {379-388}, doi = {10.1086/698657}, pmid = {30125234}, issn = {1537-5323}, abstract = {The timing and synchrony of mating activity in a population may vary both within and among years. With the exception of masting species, in which reproductive activity fluctuates dramatically among years, mating synchrony is typically studied within years. However, opportunities to mate also vary among years in nonmasting iteroparous species. We demonstrate that studying only within-year flowering synchrony fails to accurately quantify variation in mating opportunity in an experimental population ([Formula: see text]) of a nonmasting species, Echinacea angustifolia. We quantified individuals' synchrony of flowering within and among years and partitioned the contribution of each measure to mean daily mating potential, the number of potential mates per individual per day, averaged over every day that it flowered during the 11-year study period. Individual within- and among-year synchrony displayed wide variation and were weakly correlated. In particular, among-year synchrony explained 39% more variation in mean daily mating potential than did within-year synchrony. Among-year synchrony could have underappreciated significance for mating dynamics in nonmasting species.}, } @article {pmid30125233, year = {2018}, author = {Bell, KC and Demboski, JR and Cook, JA}, title = {Sympatric Parasites Have Similar Host-Associated, but Asynchronous, Patterns of Diversification.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {E106-E119}, doi = {10.1086/698300}, pmid = {30125233}, issn = {1537-5323}, abstract = {Parasitism is a common symbiotic interaction across diverse natural systems. Using a comparative evolutionary approach, we investigated the contributions of both host phylogeny and abiotic factors toward diversification of phylogenetically independent endoparasites that inhabit essentially the same physical space. We tested for host-parasite and parasite-parasite phylogenetic concordance in western North American chipmunks (Rodentia: Sciuridae) and two distantly related species of pinworms (Nematoda: Oxyurida). Deep structure in molecular phylogenies revealed signals of host-associated divergence in both parasite species, while shallower phylogeographic structure varied between the two parasites. This suggests that although these parasites experienced similar landscapes and cyclic climate processes, temporally distinctive diversification events were associated with differences in the initiation of their association with host lineages. When climate cycles initiate diversification, partially congruent, but asynchronous, host-associated parasite phylogenies may emerge.}, } @article {pmid30125232, year = {2018}, author = {Aguilar, EG and Akçay, E}, title = {Gene-Culture Coinheritance of a Behavioral Trait.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {311-320}, doi = {10.1086/698872}, pmid = {30125232}, issn = {1537-5323}, abstract = {Many physical and behavioral traits in animals, including humans, are inherited both genetically and culturally. The presence of different inheritance systems affecting the same trait can result in complex evolutionary dynamics. Here, we present a general model that elucidates the distinct roles of cultural and genetic inheritance systems and their interaction in driving the evolution of complex phenotypes. In particular, we derive a Price equation that incorporates both cultural and genetic inheritance of a phenotype where the effects of genes and culture are additive. We then use this equation to investigate whether a genetically maladaptive phenotype can evolve under dual transmission. We examine the special case of altruism using an illustrative model and show that cultural selection can overcome genetic selection when the variance in culture is sufficiently high with respect to genes. We also show that the presence of cultural transmission can modify genetic selection itself, making genetic selection more favorable to a trait than under purely genetic inheritance. Last, we consider the effect of different timescales of genetic and cultural transmission. We discuss the implications of our results for understanding the evolution of important coinherited behaviors, including how our framework can be used to generate quantitative estimates of selection pressures required for a genetically maladaptive trait to evolve.}, } @article {pmid30125231, year = {2018}, author = {Hanschen, ER and Herron, MD and Wiens, JJ and Nozaki, H and Michod, RE}, title = {Multicellularity Drives the Evolution of Sexual Traits.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {E93-E105}, doi = {10.1086/698301}, pmid = {30125231}, issn = {1537-5323}, abstract = {From the male peacock's tail plumage to the floral displays of flowering plants, traits related to sexual reproduction are often complex and exaggerated. Why has sexual reproduction become so complicated? Why have such exaggerated sexual traits evolved? Early work posited a connection between multicellularity and sexual traits such as anisogamy (i.e., the evolution of small sperm and large eggs). Anisogamy then drives the evolution of other forms of sexual dimorphism. Yet the relationship between multicellularity and the evolution of sexual traits has not been empirically tested. Given their extensive variation in both multicellular complexity and sexual systems, the volvocine green algae offer a tractable system for understanding the interrelationship of multicellular complexity and sex. Here we show that species with greater multicellular complexity have a significantly larger number of derived sexual traits, including anisogamy, internal fertilization, and secondary sexual dimorphism. Our results demonstrate that anisogamy repeatedly evolved from isogamous multicellular ancestors and that anisogamous species are larger and produce larger zygotes than isogamous species. In the volvocine algae, the evolution of multicellularity likely drives the evolution of anisogamy, and anisogamy subsequently drives secondary sexual dimorphism. Multicellularity may set the stage for the overall diversity of sexual complexity throughout the Tree of Life.}, } @article {pmid30125230, year = {2018}, author = {Mouton, JC and Martin, TE}, title = {Fitness Consequences of Interspecific Nesting Associations among Cavity-Nesting Birds.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {389-396}, doi = {10.1086/698873}, pmid = {30125230}, issn = {1537-5323}, abstract = {Interspecific aggregations of prey may provide benefits by mitigating predation risk, but they can also create costs if they increase competition for resources or are more easily detectable by predators. Variation in predation risk and resource availability may influence the occurrence and fitness effects of aggregating in nature. Yet tests of such possibilities are lacking. Cavity-nesting birds provide an interesting test case. They compete aggressively for resources and experience low nest predation rates, which might predict dispersion, but across 19 years of study we found that they commonly aggregate by sharing nest trees. Tree sharing was more common when aspen were more abundant and was somewhat more common in years with higher nest predation risk. Nest success was higher in shared trees when nest predation risk was higher than average. Ultimately, the costs and benefits of aggregating (nest tree sharing) varied across years, and we outline hypotheses for future studies.}, } @article {pmid30125229, year = {2018}, author = {Gilman, RT and Fowler-Finn, K and Hebets, EA}, title = {A Probable Case of Incipient Speciation in Schizocosa Wolf Spiders Driven by Allochrony, Habitat Use, and Female Mate Choice.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {332-346}, doi = {10.1086/698302}, pmid = {30125229}, issn = {1537-5323}, abstract = {There is growing evidence that speciation can occur between populations that are not geographically isolated. The emergence of assortative mating is believed to be critical to this process, but how assortative mating arises in diverging populations is poorly understood. The wolf spider genus Schizocosa has become a model system for studying mechanisms of assortative mating. We conducted a series of experiments to identify the factors that control mate pair formation in a Schizocosa population that includes both ornamented and nonornamented males. We show that the population also includes two previously unrecognized female phenotypes. One female phenotype mates mostly or exclusively with ornamented males, and the other mates mostly or exclusively with unornamented males. Assortative mating within these groups is maintained by differences in maturation time, microhabitat use, and female mate preference. We conclude that the population is not a single species, as previously believed, but rather an incipient species pair with multiple overlapping mechanisms of reproductive isolation. The identification of a new incipient species pair in the well-studied and rapidly speciating Schizocosa clade presents new opportunities for the study of speciation without geographic isolation.}, } @article {pmid30125228, year = {2018}, author = {Wagner, P and Plotnick, RE and Lyons, SK}, title = {Evidence for Trait-Based Dominance in Occupancy among Fossil Taxa and the Decoupling of Macroecological and Macroevolutionary Success.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {E120-E138}, doi = {10.1086/697642}, pmid = {30125228}, issn = {1537-5323}, abstract = {Biological systems provide examples of differential success among taxa, from ecosystems with a few dominant species (ecological success) to clades that possess far more species than sister clades (macroevolutionary success). Macroecological success, the occupation by a species or clade of an unusually high number of areas, has received less attention. If macroecological success reflects heritable traits, then successful species should be related. Genera composed of species possessing those traits should occupy more areas than genera with comparable species richness that lack such traits. Alternatively, if macroecological success reflects autapomorphic traits, then generic occupancy should be a by-product of species richness among genera and occupancy of constituent species. We test this using Phanerozoic marine invertebrates. Although temporal patterns of species and generic occupancy are strongly correlated, inequality in generic occupancy typically is greater than expected. Genus-level patterns cannot be explained solely with species-level patterns. Within individual intervals, deviations between the observed and expected generic occupancy correlate with the number of lithological units (stratigraphic formations), particularly after controlling for geographic range and species richness. However, elevated generic occupancy is unrelated to or negatively associated with either generic geographic ranges or within-genus species richness. Our results suggest that shared traits among congeneric species encourage short-term macroecological success without generating short-term macroevolutionary success. A broad niche may confer high occupancy but does not necessarily promote speciation.}, } @article {pmid30125227, year = {2018}, author = {Sutton, NM and O'Dwyer, JP}, title = {Born to Run? Quantifying the Balance of Prior Bias and New Information in Prey Escape Decisions.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {321-331}, doi = {10.1086/698692}, pmid = {30125227}, issn = {1537-5323}, abstract = {Animal behaviors can often be challenging to model and predict, though optimality theory has improved our ability to do so. While many qualitative predictions of behavior exist, accurate quantitative models, tested by empirical data, are often lacking. This is likely due to variation in biases across individuals and variation in the way new information is gathered and used. We propose a modeling framework based on a novel interpretation of Bayes's theorem to integrate optimization of energetic constraints with both prior biases and specific sources of new information gathered by individuals. We present methods for inferring distributions of prior biases within populations rather than assuming known priors, as is common in Bayesian approaches to modeling behavior, and for evaluating the goodness of fit of overall model descriptions. We apply this framework to predict optimal escape during predator-prey encounters, based on prior biases and variation in what information prey use. Using this approach, we collected and analyzed data characterizing white-tailed deer (Odocoileus virginianus) escape behavior in response to human approaches. We found that distance to predator alone was not sufficient to predict deer flight response and show that the inclusion of additional information is necessary. We also compared differences in the inferred distributions of prior biases across different populations and discuss the possible role of human activity in influencing these distributions.}, } @article {pmid30125226, year = {2018}, author = {Start, D}, title = {Ontogeny and Consistent Individual Differences Mediate Trophic Interactions.}, journal = {The American naturalist}, volume = {192}, number = {3}, pages = {301-310}, doi = {10.1086/698693}, pmid = {30125226}, issn = {1537-5323}, abstract = {Ecologists use species traits to predict responses to environmental change and, ultimately, to understand the composition of biological communities. However, this ignores known and substantial intraspecific variation that can have important consequences for species interactions and community composition. This within-species variation results from two distinct sources: ontogeny and consistent individual differences. Ontogeny and consistent differences interact to produce phenotypes, but the community-level consequences of this interaction have not been studied. Using larval dragonfly communities, I investigate patterns of intraguild predation by manipulating (1) consistent individual differences in activity rate and (2) the ontogeny of the focal and interacting species. I show that activity rate is a consistent individual trait but that the effect of activity rate on intraguild predation depends on the functional role of an organism in the community (predator or prey). An organism's functional role itself varies across ontogeny of both the focal and interacting individuals. I suggest that ontogeny and consistent individual differences interact to produce intraspecific variation, with consequences for species interactions, communities, and eco-evolutionary dynamics.}, } @article {pmid30125139, year = {2018}, author = {Oxburgh, L}, title = {Kidney Nephron Determination.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {427-450}, doi = {10.1146/annurev-cellbio-100616-060647}, pmid = {30125139}, issn = {1530-8995}, support = {R01 DK078161/DK/NIDDK NIH HHS/United States ; }, abstract = {The nephron is a multifunctional filtration device equipped with an array of sophisticated sensors. For appropriate physiological function in the human and mouse, nephrons must be stereotypically arrayed in large numbers, and this essential structural property that defines the kidney is determined during its fetal development. This review explores the process of nephron determination in the fetal kidney, providing an overview of the foundational literature in the field as well as exploring new developments in this dynamic research area. Mechanisms that ensure that a large number of nephrons can be formed from a small initial number of progenitor cells are central to this process, and the question of how the nephron progenitor cell population balances epithelial differentiation with renewal in the progenitor state is a subject of particular interest. Key growth factor signaling pathways and transcription factor networks are discussed.}, } @article {pmid30125138, year = {2018}, author = {Rak, R and Dahan, O and Pilpel, Y}, title = {Repertoires of tRNAs: The Couplers of Genomics and Proteomics.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {239-264}, doi = {10.1146/annurev-cellbio-100617-062754}, pmid = {30125138}, issn = {1530-8995}, abstract = {The pool of transfer RNA (tRNA) molecules in cells allows the ribosome to decode genetic information. This repertoire of molecular decoders is positioned in the crossroad of the genome, the transcriptome, and the proteome. Omics and systems biology now allow scientists to explore the entire repertoire of tRNAs of many organisms, revealing basic exciting biology. The tRNA gene set of hundreds of species is now characterized, in addition to the tRNA genes of organelles and viruses. Genes encoding tRNAs for certain anticodon types appear in dozens of copies in a genome, while others are universally absent from any genome. Transcriptome measurement of tRNAs is challenging, but in recent years new technologies have allowed researchers to determine the dynamic expression patterns of tRNAs. These advances reveal that availability of ready-to-translate tRNA molecules is highly controlled by several transcriptional and posttranscriptional regulatory processes. This regulation shapes the proteome according to the cellular state. The tRNA pool profoundly impacts many aspects of cellular and organismal life, including protein expression level, translation accuracy, adequacy of folding, and even mRNA stability. As a result, the shape of the tRNA pool affects organismal health and may participate in causing conditions such as cancer and neurological conditions.}, } @article {pmid30124888, year = {2018}, author = {}, title = {Genomics of Parallel Ecological Speciation in Lake Victoria Cichlids.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2594}, doi = {10.1093/molbev/msy135}, pmid = {30124888}, issn = {1537-1719}, } @article {pmid30124863, year = {2018}, author = {McGrath, C}, title = {Up in the Air: The Emerging Science of Dust and Sandstorm Microbes.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2008-2009}, pmid = {30124863}, issn = {1759-6653}, mesh = {*Dust ; Health ; Humans ; Metagenomics ; *Microbiota ; Soil Microbiology ; }, } @article {pmid30124839, year = {2018}, author = {Yu, W and Wu, JH and Zhang, J and Yang, W and Chen, J and Xiong, J}, title = {A meta-analysis reveals universal gut bacterial signatures for diagnosing the incidence of shrimp disease.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy147}, pmid = {30124839}, issn = {1574-6941}, abstract = {Increasing evidence indicates that dysbiosis in the gut microbiota contributes to disease pathogenesis. However, whether certain taxa are universally indicative of diverse shrimp diseases is unclear thus far. We conducted a meta-analysis to explore the divergences in gut microbiota between healthy and diseased shrimp. The gut bacterial communities of healthy shrimp varied significantly (P < 0.05 in each comparison) over ontogenetic stages, and were distinct from the corresponding diseased cohorts at each life stage. Both phylogenetic-based mean nearest taxon distance analysis and multivariate dispersion testing revealed that shrimp disease weakened the relative importance of deterministic processes in governing the gut microbiota. Partitioning beta diversity analysis indicated that temporal turnover governed the gut microbiota as healthy shrimp aged, whereas this trend was retarded in disease cohorts, concurrent with an increased nestedness. After ruling out the age-discriminatory and disease-specific orders, a high diagnosed accuracy (85.9%) of shrimp health status was achieved by using the profiles of the 11 universal disease-discriminatory orders as independent variables. These findings improve current understanding of how disease alters the ecological processes that govern the shrimp gut microbiota assembly, and exemplifies the potential application of universal bacterial signatures to diagnose the incidence of diverse shrimp diseases, irrespective of causal pathogens.}, } @article {pmid30124835, year = {2018}, author = {Stewart, LC and Houghton, K and Carere, CR and Power, JF and Chambefort, I and Stott, MB}, title = {Interaction between ferruginous clay sediment and an iron-reducing hyperthermophilic Pyrobaculum sp. in a terrestrial hot spring.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy160}, pmid = {30124835}, issn = {1574-6941}, abstract = {Green-coloured sediments in low-temperature geothermal surface features are typically indicative of photosynthetic activity. A near-boiling (89-93°C), alkali-chloride spring in the Taupō Volcanic Zone, New Zealand, was observed to have dark green sediments despite being too hot to support any known photosynthetic organisms. Analysis of aqueous and sediment microbial communities via 16S rRNA amplicon sequencing revealed them to be dominated by Aquifex spp., a genus of known hyperthermophilic hydrogen-oxidisers (69%-91% of operational taxonomic units (OTUs)), followed by groups within the Crenarchaeota (3%-20%), including the known iron-reducing genus Pyrobaculum. Cultivation experiments suggest that the green colouration of clay sediments in this spring may be due in part to ferruginous clays and associated compounds serving as substrates for the iron-reducing activity of low-abundance Pyrobaculum spp. These findings demonstrate the dynamic nature of microbe-mineral interactions in geothermal environments, and the potential ability of the rarer biosphere (1%-2% of observed sequences, cell densities of 450-33 000 g-1 sediment) to influence mineral formation at a macro-scale.}, } @article {pmid30124822, year = {2018}, author = {Tas, N and Brandt, BW and Braster, M and van Breukelen, BM and Röling, WFM}, title = {Subsurface landfill leachate contamination affects microbial metabolic potential and gene expression in the Banisveld aquifer.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy156}, pmid = {30124822}, issn = {1574-6941}, abstract = {Microbial communities in groundwater ecosystems can develop the capacity to degrade complex mixtures of chemicals resulting from pollution by landfill leachate. Monitoring this natural attenuation requires insight into the metabolic potential and activity of microbial communities. We contrasted the metagenomes and metatranscriptomes from a leachate-polluted aquifer downstream of the Banisveld (the Netherlands) landfill with uncontaminated groundwater, which revealed changes in microbial genomic content and activity. Banisveld landfill leachate contains mono-aromatic hydrocarbons and the assessment of natural attenuation of these compounds in the aquifer had been a focal point of research. In the contaminated groundwater, active microbial functions were the ones involved in degradation of complex carbon substrates and organic pollutants. We found that benzylsuccinate synthase genes-involved in the catabolism of toluene-were highly expressed close to the source of contamination, confirming the ongoing natural attenuation of organic mono-aromatic hydrocarbon pollution in this aquifer. Additionally, metatranscriptomes were indicative of phosphorus limitation that can constrain total microbial activity and agree with the low phosphate concentrations (<0.4 μmol/L) in this aquifer. Through the application of metagenomics and metatranscriptomics, we were able to determine functional potential and expression patterns to assess the natural attenuation processes and constraints on microbial communities.}, } @article {pmid30124819, year = {2018}, author = {Trautwein, K and Hensler, M and Wiegmann, K and Skorubskaya, E and Wöhlbrand, L and Wünsch, D and Hinrichs, C and Feenders, C and Müller, C and Schell, K and Ruppersberg, H and Vagts, J and Koßmehl, S and Steinbüchel, A and Schmidt-Kopplin, P and Wilkes, H and Hillebrand, H and Blasius, B and Schomburg, D and Rabus, R}, title = {The marine bacterium Phaeobacter inhibens secures external ammonium by rapid buildup of intracellular nitrogen stocks.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, pmid = {30124819}, issn = {1574-6941}, abstract = {Reduced nitrogen species are key nutrients for biological productivity in the oceans. Ammonium is often present in low and growth-limiting concentrations, albeit peaks occur during collapse of algal blooms or via input from deep sea upwelling and riverine inflow. Autotrophic phytoplankton exploit ammonium peaks by storing nitrogen intracellularly. In contrast, the strategy of heterotrophic bacterioplankton to acquire ammonium is less well understood. This study revealed the marine bacterium Phaeobacter inhibens DSM 17395, a Roseobacter group member, to have already depleted the external ammonium when only ∼⅓ of the ultimately attained biomass is formed. This was paralleled by a three-fold increase in cellular nitrogen levels and rapid buildup of various nitrogen-containing intracellular metabolites (and enzymes for their biosynthesis) and biopolymers (DNA, RNA and proteins). Moreover, nitrogen-rich cells secreted potential RTX proteins and the antibiotic tropodithietic acid, perhaps to competitively secure pulses of external ammonium and to protect themselves from predation. This complex response may ensure growing cells and their descendants exclusive provision with internal nitrogen stocks. This nutritional strategy appears prevalent also in other roseobacters from distant geographical provenances and could provide a new perspective on the distribution of reduced nitrogen in marine environments, i.e. temporary accumulation in bacterioplankton cells.}, } @article {pmid30124817, year = {2018}, author = {Cirri, E and Vyverman, W and Pohnert, G}, title = {Biofilm interactions-bacteria modulate sexual reproduction success of the diatom Seminavis robusta.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy161}, pmid = {30124817}, issn = {1574-6941}, abstract = {Marine biofilms are complex multi-species communities where chemical signaling regulates a substantial share of interactions. The involved natural products represent targets for competition strategies by signal interference. Diatoms, that often dominate biofilms, rely on a complex pheromone system during sexual reproduction, involving synchronizing and attracting metabolites. The present study addresses the effect of bacteria on sexual reproduction of the model pennate diatom Seminavis robusta. We observe that sexual reproduction is most efficient under axenic conditions. Bacteria isolated from field collected biofilms modulate sexual reproduction in the algae. A species-specific effect on the diatom mating efficiency could be observed, with Maribactersp. and Marinobactersp. significantly reducing the sexual reproduction rate. Spent medium from these bacteria has the same effect, demonstrating that chemically mediated cross kingdom interactions take place. In contrast, proportion of auxospores. We further observed a lower concentration of the diatom attraction pheromone diproline in the presence of bacteria compared to axenic conditions. In agreement, the Seminavis-associated bacterial community as well as isolated bacterial strains degraded the pheromone over time. Our results highlight that the pheromone system of diatoms is subject to interference strategies of the associated bacterial community by modulation of the signal landscape.}, } @article {pmid30124812, year = {2018}, author = {Kavazos, CRJ and Huggett, MJ and Mueller, U and Horwitz, P}, title = {Bacterial and ciliate biofilm community structure at different spatial levels of a salt lake meta-community.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy148}, pmid = {30124812}, issn = {1574-6941}, abstract = {Meta-communities are assembled along an ecological scale that determines local and regional diversity. Spatial patterns have been detected in planktonic bacterial communities at distances <20 m, but little is known about the occurrence of similar variation for other microbial groups and changes in microbial meta-community assembly at different levels of a meta-community. To examine this variation, the biofilm of eight saline ponds were used to investigate processes shaping diversity within ponds (β) and between ponds (δ). Bacterial and ciliate communities were assessed using ARISA and T-RFLP respectively, while diversity partitioning methods were used to examine the importance of taxonomic turnover and variation partitioning was used to distinguish spatial from environmental determinants. The results show that turnover is important for determining β- and δ-diversity of biofilms. Spatial factors are important drivers of bacterial β-diversity but were unimportant for ciliate β-diversity. Environmental variation was a strong determinant of bacterial and ciliate δ-diversity, suggesting sorting processes are important for assembling pond communities. Determinants of diversity in bacteria are not universal for ciliates, suggesting higher functional redundancy of bacteria or the greater niche breadth of ciliates may be important in discriminating assembly processes between the two organisms.}, } @article {pmid30124811, year = {2018}, author = {Watanabe, K and Suzuki, H and Nishida, T and Mishima, M and Tachibana, M and Fujishima, M and Shimizu, T and Watarai, M}, title = {Identification of novel Legionella genes required for endosymbiosis in Paramecium based on comparative genome analysis with Holospora spp.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy162}, pmid = {30124811}, issn = {1574-6941}, abstract = {The relationship between Legionella and protist hosts has a huge impact when considering the infectious risk in humans because it facilitates the long-term replication and survival of Legionella in the environment. The ciliate Paramecium is considered to be a protist host for Legionella in natural environments, but the details of their endosymbiosis are largely unknown. In this study, we determined candidate Legionella pneumophila genes that are likely to be involved in the establishment of endosymbiosis in Paramecium caudatum by comparing the genomes of Legionella spp. and Holospora spp. that are obligate endosymbiotic bacteria in Paramecium spp. Among the candidate genes, each single deletion mutant for five genes (lpg0492, lpg0522, lpg0523, lpg2141 and lpg2398) failed to establish endosymbiosis in P. caudatum despite showing intracellular growth in human macrophages. The mutants exhibited no characteristic changes in terms of their morphology, multiplication rate or capacity for modulating the phagosomes in which they were contained, but their resistance to lysozyme decreased significantly. This study provides insights into novel factors required by L. pneumophila for endosymbiosis in P. caudatum, and suggests that endosymbiotic organisms within conspecific hosts may have shared genes related to effective endosymbiosis establishment.}, } @article {pmid30124400, year = {2018}, author = {Jung, MY and Islam, MA and Gwak, JH and Kim, JG and Rhee, SK}, title = {Nitrosarchaeum koreense gen. nov., sp. nov., an aerobic and mesophilic, ammonia-oxidizing archaeon member of the phylum Thaumarchaeota isolated from agricultural soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3084-3095}, doi = {10.1099/ijsem.0.002926}, pmid = {30124400}, issn = {1466-5034}, mesh = {Agriculture ; Ammonia/*metabolism ; Archaea/*classification/genetics/isolation & purification ; Base Composition ; Genes, Archaeal ; Glyceryl Ethers/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Soil/chemistry ; *Soil Microbiology ; }, abstract = {A mesophilic, chemolithoautotrophic, neutrophilic and aerobic ammonia-oxidizing archaeon, designated strain MY1T, was isolated from agricultural soil. Microscopic observation revealed short, rod-shaped cells with a diameter of 0.3-0.5 µm and length of 0.6-1.0 µm. The isolate had no flagella and pili, and possessed no genes associated with archaeal flagella synthesis. The major membrane lipids consisted mainly of the glycerol dibiphytanyl glycerol tetraether (GDGT) lipids GDGT-0 to GDGT-4 and crenarchaeol. The major intact polar lipids (IPLs) were determined as hexose plus phosphohexose IPL and dihexose IPL. Strain MY1T obtains energy by aerobically oxidizing ammonia and carbon by fixing CO2. An optimal growth was observed at 25 °C, at pH 7 and with 0.2-0.4 % (w/v) salinity that corresponds with its terrestrial habitat. The addition of α-keto acids was necessary to stimulate growth. The strain tolerated ammonium and nitrite concentrations up to 10 and 5 mM, respectively. The MY1T genome has a DNA G+C content of 32.7 mol%. Phylogenetic analysis based on the 16S rRNA gene showed that strain MY1T belongs to the family Nitrosopumilaceaeof the phylum Thaumarchaeota, sharing the highest 16S rRNA gene sequence similarity (96.6-97.1 %) with marine isolates of the genus Nitrosopumilus. The average nucleotide identity was 78 % between strain MY1T and Nitrosopumilus maritimus SCM1T, indicating distant relatedness. Based on the phenotypic, phylogenetic and genomic analyses, it was concluded that strain MY1T belongs to the novel genus Nitrosarchaeum, under which the name Nitrosarchaeum koreense sp. nov. is proposed as the type species. The type strain is MY1T (=JCM 31640T=KCTC 4249T).}, } @article {pmid30124399, year = {2018}, author = {Zhang, X and Tu, B and Dai, LR and Lawson, PA and Zheng, ZZ and Liu, LY and Deng, Y and Zhang, H and Cheng, L}, title = {Petroclostridium xylanilyticum gen. nov., sp. nov., a xylan-degrading bacterium isolated from an oilfield, and reclassification of clostridial cluster III members into four novel genera in a new Hungateiclostridiaceae fam. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3197-3211}, doi = {10.1099/ijsem.0.002966}, pmid = {30124399}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Clostridiales/*classification/genetics/isolation & purification ; Clostridium/genetics ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Oil and Gas Fields/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/microbiology ; Xylans/metabolism ; }, abstract = {A rod-shaped, Gram-stain-positive, obligately anaerobic, xylan-degrading bacterium, SK-Y3T, was isolated from oily-sludge of Shengli oilfield, China. Optimum growth occurred at 50 °C, at pH 7.5 and without addition of NaCl. The predominant cellular fatty acids of strain SK-Y3T were iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0, and the main polar lipids were glycolipids (GL), lipids (L), phosphatidylglycerol (PG) and diphosphatidylglycerol (DPG); no respiratory quinones were detected. The genomic DNA G+C content was 37.2 mol%. Phylogenetic analysis of 16S rRNA gene sequences showed that strain SK-Y3T belongs to clostridial cluster III, exhibiting 91-92% sequence similarity to the most closely related species, namely Clostridium clariflavum, Clostridium straminisolvens and Acetivibrio cellulolyticus. Based on distinct physiological and phylogenetic differences from the aforementioned described taxa, strain SK-Y3T (=DSM 103557T=ACCC 19952T) is proposed as the type strain of a novel species of a new genus, Petroclostridium xylanilyticum gen. nov., sp. nov. Furthermore, analysis through 16S rRNA gene, ribosomal protein and whole genome sequences indicated that clostridial cluster III members should be reclassified into four novel genera for which the names Hungateiclostridium gen. nov., Thermoclostridium gen. nov., Ruminiclostridium gen. nov. and Pseudoclostridium gen. nov. are proposed. In combination with the genera Anaerobacterium, Cellulosibacter, Ercella, Fastidiosipila, Mageeibacillus, Pseudobacteroides, Petroclostridium and Saccharofermentans, clostridial cluster III members formed a monophyletic clade within the order Clostridiales but that was clearly distinguished from other Ruminococcaceae members, which is proposed as a novel family, Hungateiclostridiaceae fam. nov.}, } @article {pmid30124398, year = {2018}, author = {Cai, YM and Gao, ZH and Chen, MH and Huang, YX and Qiu, LH}, title = {Dyella halodurans sp. nov., isolated from lower subtropical forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3237-3242}, doi = {10.1099/ijsem.0.002969}, pmid = {30124398}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Genes, Bacterial ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; Xanthomonadaceae/*classification/genetics/isolation & purification ; }, abstract = {A Gram-stain-negative, aerobic, non-endospore-forming, motile by a polar flagellum, rod-shaped bacterium, designated strain DHOG02T, which produced yellow-pigmented colonies, was isolated from a soil sample collected from the lower subtropical forest of the Dinghushan Biosphere Reserve, Guangdong Province, PR China. Strain DHOG02T grew at 12-37 °C, pH 4-9 and 0-4 % (w/v) NaCl, with optima at 28 °C, pH 6-7 and 0.5 % (w/v) NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that this strain formed a clade with Dyella lipolytica DHOB07T and Dyella jejuensis JP1T, with sequence similarities of 98.0 and 97.4 %, respectively. The result of the concatenated partial gyrB, lepA and recA gene sequence analysis confirmed that strain DHOG02T belongs to the genus Dyella, but is distinct from all currently known species of the genus. The G+C content of the genomic DNA was 62 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified aminophospholipid and phospholipid. Ubiquinone-8 was the only respiratory quinone detected, and iso-C15 : 0, iso-C17 : 1ω9c and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) were the major fatty acids, all of which supported the affiliation of strain DHOG02T to the genus Dyella. On the basis of the evidence presented here, strain DHOG02T represents a novel species of the genus Dyella, for which the name Dyella halodurans sp. nov. is proposed. The type strain is DHOG02T (=NBRC 111474T=CGMCC 1.15435T).}, } @article {pmid30124397, year = {2018}, author = {Ouhibi, S and Santos, C and Ghali, R and Soares, C and Hedhili, A and Paterson, R and Lima, N}, title = {Penicillium tunisiense sp. nov., a novel species of Penicillium section Ramosa discovered from Tunisian orchard apples.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3217-3225}, doi = {10.1099/ijsem.0.002962}, pmid = {30124397}, issn = {1466-5034}, mesh = {Calmodulin/genetics ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Malus/*microbiology ; Mycological Typing Techniques ; Penicillium/*classification/genetics/isolation & purification ; *Phylogeny ; Sequence Analysis, DNA ; Tubulin/genetics ; Tunisia ; }, abstract = {Two similar Penicillium isolates could not be identified as previously described species in a survey of orchard apples from Tunisia for patulin-producing fungi. These isolates are described as novel species using multilocus DNA sequence analysis of partial β-tubulin, calmodulin and nuclear ribosomal internal transcribed spacer regions; and morphological, physiological and biochemical characteristics. The isolates were considered negative for patulin production since the IDH gene fragment was not detected and the compound detected at the same retention time of patulin (14.9 min) showed a different UV spectrum using U-HPLC/UV-DAD. In terms of phylogeny, the two isolates clustered with Penicillium section Ramosa and are closely related to Penicillium chroogomphum, Penicillium lenticrescens and Penicillium soppii. Furthermore, their macro- and micromorphological traits differed from these species. Hence, the isolates represent a novel species in Penicillium section Ramosa and the name Penicillium tunisiense sp. nov. is proposed, with the type strain MUM 17.62T (=ITEM 17445T).}, } @article {pmid30124170, year = {2018}, author = {Regidi, S and Ravindran, S and Vijayan, AL and Maya, V and Sreedharan, L and Varghese, J and Ramaswami, K and Gopi, M}, title = {Effect of lyophilization on HRP-antibody conjugation: an enhanced antibody labeling technology.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {596}, pmid = {30124170}, issn = {1756-0500}, mesh = {*Antibodies ; Electrophoresis, Polyacrylamide Gel ; Enzyme-Linked Immunosorbent Assay ; Freeze Drying ; *Horseradish Peroxidase ; }, abstract = {OBJECTIVE: Immunoassay usually deal with the antibody labeling with various reporter molecules, one such useful reporter molecule is horseradish peroxidase (HRPO). Conjugating enzyme with antibody without losing its enzymatic activity is a challenging task. Our aim is to modify existing classical method of conjugating antibodies with HRP to enhance immunoassay techniques with better sensitivity. We used chemicals such as sodium meta periodate to generate aldehyde group by oxidation of carbohydrate moieties on HRPO. The activated form of HRPO is lyophilized and then mixed with 1 mg/ml concentration of antibodies to be conjugate.

RESULTS: After confirming chemical modification of conjugates via UV-Spec and SDS-PAGE independent molecules were used for conjugation and HRP-antibody conjugate. Finally, enzymatic activity of HRP-antibody conjugate was confirmed by performing direct ELISA. Functional properties were analyzed using ELISA with dilution of 1:5000, whereas the conjugate prepared by existing method of conjugation worked with as low dilution of 1:25 with a p value highly significant (< 0.001) for classical verses modified method of conjugation preparation. Collectively, this study showed the enhanced ability of antibody to bind more number of HRPO with an additional step of lyophilization in the regular conjugation protocol. Future exploration are necessary on wide range of IgG antibodies.}, } @article {pmid30124169, year = {2018}, author = {Salzberg, SL}, title = {Open questions: How many genes do we have?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {94}, pmid = {30124169}, issn = {1741-7007}, support = {R01 HG006677/HG/NHGRI NIH HHS/United States ; }, abstract = {Seventeen years after the initial publicationx of the human genome, we still haven't found all of our genes. The answer turns out to be more complex than anyone had imagined when the Human Genome Project began.}, } @article {pmid30124168, year = {2018}, author = {Flatt, T and Partridge, L}, title = {Horizons in the evolution of aging.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {93}, pmid = {30124168}, issn = {1741-7007}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Between the 1930s and 50s, evolutionary biologists developed a successful theory of why organisms age, firmly rooted in population genetic principles. By the 1980s the evolution of aging had a secure experimental basis. Since the force of selection declines with age, aging evolves due to mutation accumulation or a benefit to fitness early in life. Here we review major insights and challenges that have emerged over the last 35 years: selection does not always necessarily decline with age; higher extrinsic (i.e., environmentally caused) mortality does not always accelerate aging; conserved pathways control aging rate; senescence patterns are more diverse than previously thought; aging is not universal; trade-offs involving lifespan can be 'broken'; aging might be 'druggable'; and human life expectancy continues to rise but compressing late-life morbidity remains a pressing challenge.}, } @article {pmid30122551, year = {2018}, author = {Glennon, EKK and Dankwa, S and Smith, JD and Kaushansky, A}, title = {Opportunities for Host-targeted Therapies for Malaria.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {843-860}, pmid = {30122551}, issn = {1471-5007}, support = {R01 GM101183/GM/NIGMS NIH HHS/United States ; R01 HL130488/HL/NHLBI NIH HHS/United States ; T32 AI007509/AI/NIAID NIH HHS/United States ; }, mesh = {Antimalarials/*immunology/pharmacology ; *Drug Delivery Systems ; Host-Parasite Interactions/drug effects ; Humans ; Immunologic Factors/pharmacology ; }, abstract = {Despite the recent successes of artemisinin-based antimalarial drugs, many still die from severe malaria, and eradication efforts are hindered by the limited drugs currently available to target transmissible gametocyte parasites and liver-resident dormant Plasmodium vivax hypnozoites. Host-targeted therapy is a new direction for infectious disease drug development and aims to interfere with host molecules, pathways, or networks that are required for infection or that contribute to disease. Recent advances in our understanding of host pathways involved in parasite development and pathogenic mechanisms in severe malaria could facilitate the development of host-targeted interventions against Plasmodium infection and malaria disease. This review discusses new opportunities for host-targeted therapeutics for malaria and the potential to harness drug polypharmacology to simultaneously target multiple host pathways using a single drug intervention.}, } @article {pmid30122257, year = {2018}, author = {Wise, MN}, title = {Afterward: Humboldt was Right.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {82-86}, doi = {10.1016/j.shpsa.2018.05.011}, pmid = {30122257}, issn = {0039-3681}, abstract = {Alexander von Humboldt provides a point of reference for questions that arise when reflecting on the papers in this special issue on "Experiencing the Global Environment," for he aimed to integrate local and global experience and qualitative and quantitative observation in his conceptions of physiognomy and of instruments. What are we to understand by direct experience? How do we draw the limits of our senses, whether in the larger world or internally? Does recent scholarly interest in distributed cognition illuminate the distributed experience of global phenomena obtained through mapping? How do our concepts shape our experience, whether local or global? Finally, do recent trends in the sciences, emphasizing complexity and contingency, tend to make traditional tensions between local and global priorities and between qualitative and quantitative description less relevant? Humboldt would have thought so.}, } @article {pmid30122256, year = {2018}, author = {Creager, ANH}, title = {Human bodies as chemical sensors: A history of biomonitoring for environmental health and regulation.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {70-81}, doi = {10.1016/j.shpsa.2018.05.010}, pmid = {30122256}, issn = {0039-3681}, abstract = {The testing of human blood and urine for signs of chemical exposure has become the "gold standard" of environmental public health, leading to ongoing population studies in the US and Europe. Such methods first emerged over a century ago in medical and occupational contexts, as a means to calibrate drug doses for patients and prevent injury to workers from chemical or radiation exposure. This paper analyzes how human bodies have come to serve as unconscious sensors of their environments: containers of chemical information determined by expert testers. As seen in the case of lead testing in the US, these bodily traces of contaminants can provide compelling evidence about dangerous exposures in everyday life, useful in achieving stronger regulation of industry. The use of genetic testing of workers by Dow Chemical provides an example of industry itself undertaking biomonitoring, though the company discontinued the program at the same time its studies indicated chromosomal damage in connection with occupational exposure to certain chemicals. In this case and others, biomonitoring raises complex questions about informing subjects, interpreting exposure in the many cases for which health effects at low doses are unknown, and who should take responsibility for protection, compensation, or remediation. Further, the history of biomonitoring complicates how we understand human 'experience' of the global environment by pointing to the role of non-sensory-yet detectable-bodily exposures.}, } @article {pmid30122255, year = {2018}, author = {Camprubí, L}, title = {Experiencing deep and global currents at a 'Prototypical Strait', 1870s and 1980s.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {6-17}, doi = {10.1016/j.shpsa.2018.05.004}, pmid = {30122255}, issn = {0039-3681}, abstract = {Deep ocean currents are not accessible to direct human perception. Their insertion into global structures of circulation is even more profoundly removed from individual sensorial experience. But oceanographers tend to use wider concepts of experience to include instruments, traditions of observation and theoretical models. Historians and philosophers of science, as well as STS scholars, have also redefined scientific experience as operational and collective transformations of parts of the world around us into fragments of larger bodies of knowledge. This paper pursues this definition to follow the instrumental and epistemological resources available to those "observing" deep-water circulation at the Strait of Gibraltar in two very distinct moments, ca. 1870 and ca. 1985, respectively through the works of scientists like William B. Carpenter and the transnational team involved in the Gibraltar Experiment. Detecting and mapping the Gibraltar undercurrent necessitated taking data of temperature and salinity as proxies for masses of water. Making it relevant to world ocean currents required the use of models and moving across scales. In both contexts, empires of global reach provided the globalizing motivations and infrastructures.}, } @article {pmid30122254, year = {2018}, author = {Fan, FT}, title = {Can animals predict earthquakes?: Bio-sentinels as seismic sensors in communist China and beyond.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {58-69}, doi = {10.1016/j.shpsa.2018.05.009}, pmid = {30122254}, issn = {0039-3681}, abstract = {This paper examines the international research on abnormal animal behavior prior to earthquakes, with a focus on Chinese seismology during the Cultural Revolution. China experienced a series of powerful earthquakes in the 1960s and 1970s; in response, its scientists developed approaches to earthquake prediction, including the use of bio-sentinels. The paper demonstrates that Chinese seismology did not treat an earthquake simply as a geophysical event, but rather as an amalgam of environmental phenomena, including sensory experiences. Hence, distributive experience and sensory networks of humans and bio-sentinels constituted an important component of studying the environment. This historical case suggests insights into bio-monitoring of the global environment.}, } @article {pmid30122253, year = {2018}, author = {Aronova, E}, title = {Earthquake prediction, biological clocks, and the cold war psy-ops: Using animals as seismic sensors in the 1970s California.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {50-57}, doi = {10.1016/j.shpsa.2018.05.008}, pmid = {30122253}, issn = {0039-3681}, abstract = {A familiar story of seismology is that of a small field originally focused on local studies of earthquakes through diverse disciplinary perspectives being transformed, in the second half of the twentieth century, into a highly specialized field focused on global studies of the earth's deep interior via sophisticated instruments and transnational networks of seismological stations. Against this backdrop, this essay offers a complementing account, highlighting the significance of local circumstances and disciplinary agendas that were contingent not only on transformations in the geophysical sciences but also on the concurrently changing biological sciences during the Cold War. Using examples of the studies of unusual animal behavior prior to earthquakes conducted under the auspices of the US Geological Survey on the West Coast of the United States in the 1970s, this essay examines a variety of motivations behind the attempts to bridge geophysics and biology. These examples illustrate the ways in which earthquake prediction became entangled with concerns over the use of seismological data, pioneering research on biological rhythms, and the troubled field of Cold War-driven military brain studies.}, } @article {pmid30122252, year = {2018}, author = {Lehmann, P}, title = {Average rainfall and the play of colors:Colonial experience and global climate data.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {38-49}, doi = {10.1016/j.shpsa.2018.05.007}, pmid = {30122252}, issn = {0039-3681}, abstract = {This paper examines the co-construction of global and local views of the weather and climate at the turn of the twentieth century through a history of data gathering efforts in the German colonies in Africa. While both governmental officials and metropolitan practitioners aimed at producing standardized - and thus globally comparable and economically useful - data in different environments, these efforts often tended to break down in practice. Rather than being able to turn the field into a finely tuned laboratory, both European and African data gatherers were confronted with complex and challenging environmental and institutional realities. Faced with these difficulties, colonial practitioners tended to embrace alternative strategies of recording weather conditions, which placed a higher value on individual sensory perception and qualitative descriptions. Thus, in a seemingly paradoxical dynamic, the attempts to gather quantitative colonial data for global maps and models also facilitated the development of a particular colonial approach to climatology that highlighted local specificities and direct embodied experience.}, } @article {pmid30122251, year = {2018}, author = {Benson, ES}, title = {Re-situating fieldwork and re-narrating disciplinary history in global mega-geomorphology.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {28-37}, doi = {10.1016/j.shpsa.2018.05.006}, pmid = {30122251}, issn = {0039-3681}, abstract = {In 1985, more than thirty geomorphologists, planetary scientists, and remote sensing specialists gathered at a conference center in Oracle, Arizona, to discuss an emerging area of research that they called "mega-geomorphology." Building on a conference of the same name held in London in 1981, they argued that new techniques of remote sensing and insights emerging from the study of extraterrestrial planets had created opportunities for geomorphology to broaden its spatial and temporal scope. This new approach was, however, neither unproblematic nor uncontested. In the discussions around mega-geomorphology that took place in the mid-1980s, the perceived conflict between the use of remote-sensing techniques to observe phenomena on vast spatial scales, on one hand, and the disciplinary centrality of fieldwork and field experience to geomorphology, on the other, was a recurrent theme. In response, mega-geomorphologists attempted to re-situate fieldwork and re-narrate disciplinary histories in such a way as to make remote sensing and planetary science not only compatible with geomorphological traditions but also means of revitalizing them. Only partially successful, these attempts reveal that the process of adopting a planetary perspective in geomorphology, as in other earth sciences, was neither straightforward nor inevitable. They also show how the field and fieldwork could remain central to geomorphology while also being extensively revised in light of new technical possibilities and theoretical frameworks.}, } @article {pmid30122250, year = {2018}, author = {Vetter, J}, title = {Experiential and cosmopolitan knowledge: The transcontinental field practices of the U.S. Bureau of Biological Survey.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {18-27}, doi = {10.1016/j.shpsa.2018.05.005}, pmid = {30122250}, issn = {0039-3681}, abstract = {Before many of the global environmental knowledge producing networks and technologies emerged later in the twentieth century, another spatially extended form of field science was implemented at a continental scale by the U.S. Bureau of Biological Survey, revealing similar tensions and dynamics. Specimens and observations from across continental spaces were integrated through railroad-based transportation and communications networks in order to map distributions of birds and mammals and delineate "life zones" stretching across the continent. At the same time that field zoologists of the Biological Survey produced this cosmopolitan scientific knowledge, they also developed an intimate, experiential knowledge of many of the places where they traveled. By following the travels of Biological Survey field parties, especially the agency's long-time chief field naturalist Vernon Bailey, during the late nineteenth and early twentieth centuries when the railroad was dominant, this paper traces the interconnections between the two ways of knowing in the Biological Survey's practice. However, the integration of these different forms of knowledge was ultimately partial and incomplete, as seen through the Survey's daily practices such as food consumption, the seasonality of survey field practice, and limitations on what types of knowledge were incorporated from lay network collaborators and field assistants.}, } @article {pmid30122249, year = {2018}, author = {Camprubí, L and Lehmann, P}, title = {The scales of experience: Introduction to the special issue Experiencing the global environment.}, journal = {Studies in history and philosophy of science}, volume = {70}, number = {}, pages = {1-5}, doi = {10.1016/j.shpsa.2018.05.003}, pmid = {30122249}, issn = {0039-3681}, abstract = {The Scales of Experience introduces the special issue Experiencing the Global Environment by focusing on three dimensions of the theme that are reflected to various degrees in the constitutive essays. First, the introduction highlights the links between the epistemological and political contexts of the historical constitution and development of the global environment (or global environments) in the earth and environmental sciences from the late nineteenth century to today. Second, it argues for a historical approach to the complex concept of scientific experience, whose mutable and contingent qualities are demonstrated by the contributions to the special volume. Lastly, the introduction presents one of the central issues to be tackled by the essays to follow: the development - and, at times, the failure - of strategies and technologies to bridge the seemingly incommensurate gulf between individual, localized experience and the all-encompassing scale of the global environment.}, } @article {pmid30122161, year = {2018}, author = {Cooper, R and Blashfield, R}, title = {The myth of Hempel and the DSM-III.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {70}, number = {}, pages = {10-19}, doi = {10.1016/j.shpsc.2018.05.008}, pmid = {30122161}, issn = {1879-2499}, mesh = {*Diagnostic and Statistical Manual of Mental Disorders ; History, 20th Century ; Philosophy/*history ; Psychiatry/*history ; }, } @article {pmid30122066, year = {2018}, author = {Lu, J and Zhang, Y and Liu, J}, title = {Interpersonal Insecurity and Risk-Taking Propensity Across Domains and Around the Globe.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918795520}, doi = {10.1177/1474704918795520}, pmid = {30122066}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Anxiety/*psychology ; Cooperative Behavior ; Emotions ; Exploratory Behavior ; Female ; Global Health ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; *Risk-Taking ; Sex Factors ; Trust ; Young Adult ; }, abstract = {During social interactions, individuals frequently experience interpersonal insecurity, including feelings of not being loved, protected, trusted, or cared for; these feelings cause numerous behavioral consequences. The present research explores the relationship between interpersonal insecurity and risk-taking propensity in multiple risk domains and around the globe based on risk-sensitivity theory and research on group identity. In Study 1, participants (N = 209) reported their interpersonal insecurity and risk-taking propensity across seven risk domains. The results show that risk-taking propensity generally increases with interpersonal insecurity. However, this relationship was negative in the cooperation domain and null in the financial domain. In Study 2 (N = 128,162), data from the World Values Survey from 77 countries reveal a positive correlation between risk-taking propensity and interpersonal insecurity with in-group members but a negative relationship between risk-taking propensity and interpersonal insecurity with out-group members.}, } @article {pmid30121809, year = {2018}, author = {Hertzler, PL and Wei, J and Droste, AP and Yuan, J and Xiang, J}, title = {Penaeid shrimp brachyury: sequence analysis and expression during gastrulation.}, journal = {Development genes and evolution}, volume = {228}, number = {5}, pages = {219-225}, pmid = {30121809}, issn = {1432-041X}, support = {Sex ratio and sterility for commercial animal production//Commonwealth Scientific and Industrial Research Organisation/International ; 863 Program, 2012AA10A404//National High-Tech Research and Development Program of China/International ; }, mesh = {Animals ; Evolution, Molecular ; Fetal Proteins/chemistry/*genetics/*metabolism ; *Gastrulation ; Genome ; Penaeidae/*growth & development ; Phylogeny ; Protein Domains ; T-Box Domain Proteins/chemistry/*genetics/*metabolism ; }, abstract = {Gastrulation occurs by a variety of morphogenetic movements, often correlated with diverse expression of the T-box transcription factor Brachyury (Bra). Bra may be expressed in ectoderm, mesoderm, or endoderm, but its role in cell fate specification or regulation of gastrulation movements has not been studied in the development of crustaceans. Penaeid shrimp (Decapoda: Dendrobranchiata: Penaeidae) develop by complete cleavage and gastrulation by invagination to a free-swimming nauplius larva. Penaeid gastrulation diverges from other decapods and from insects, occurring early at a low cell number with the formation of a radial invagination. Toward a better understanding of gastrulation movements in penaeid shrimp, bra was identified from newly available penaeid shrimp genomes and transcriptomes of Litopenaeus vannamei, Marsupenaeus japonicus, and Penaeus monodon. Additional bra homologs were obtained from the outgroups Sicyonia ingentis (Decapoda: Dendrobranchiata: Sicyoniidae) and the caridean shrimp Caridina multidentata (Decapoda: Pleocymata). The genes encoded penaeid shrimp Bra proteins of 551-552 amino acids, containing the highly conserved T-box DNA-binding region. The N-terminal Smad1-binding domain, conserved in most animals, was absent in shrimp Bra. The R1 repressor domain was the best conserved of the C-terminal regulatory domains, which were widely divergent compared to other species. The penaeid shrimp bra gene consisted of six exons, with splice sites conserved with other phyla across the animal kingdom. Real-time qPCR and FPKM analysis showed that shrimp bra mRNA was strongly expressed during gastrulation. These findings begin to address the evolution of gastrulation in shrimp at the molecular level.}, } @article {pmid30121342, year = {2018}, author = {Bover, P and Llamas, B and Thomson, VA and Pons, J and Cooper, A and Mitchell, KJ}, title = {Molecular resolution to a morphological controversy: The case of North American fossil muskoxen Bootherium and Symbos.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {70-76}, doi = {10.1016/j.ympev.2018.08.008}, pmid = {30121342}, issn = {1095-9513}, abstract = {The musk ox (Ovibos moschatus) is the only surviving member of a group of Pleistocene North American musk ox genera (Praeovibos, Ovibos, Bootherium, Euceratherium, and Soergelia) whose taxonomy is uncertain. The helmeted musk ox (Bootherium bombifrons) and the woodland musk ox (Symbos cavifrons) have been synonymised as male and female forms of a single Nearctic species found from Alaska, in the north, to Texas, in the south. However, this reclassification has not been tested using molecular data, despite the potential to use ancient DNA to examine these late Pleistocene taxa. In the present study, we sequenced mitochondrial genomes from seven subfossil musk ox specimens (originally identified as Bootherium and/or Symbos), allowing us to evaluate the identity of these muskoxen, explore their phylogeography, and estimate the timeline for their evolution. We also used nuclear genomic data to determine the sex of six of our seven samples. Ultimately, our molecular data support the synonymisation of the North American muskoxen Bootherium and Symbos.}, } @article {pmid30121341, year = {2018}, author = {Hassanin, A and Houck, ML and Tshikung, D and Kadjo, B and Davis, H and Ropiquet, A}, title = {Multi-locus phylogeny of the tribe Tragelaphini (Mammalia, Bovidae) and species delimitation in bushbuck: Evidence for chromosomal speciation mediated by interspecific hybridization.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {96-105}, doi = {10.1016/j.ympev.2018.08.006}, pmid = {30121341}, issn = {1095-9513}, abstract = {The bushbuck is the most widespread bovid species in Africa. Previous mitochondrial studies have revealed a polyphyletic pattern suggesting the possible existence of two distinct species. To assess this issue, we have sequenced 16 nuclear genes and one mitochondrial fragment (cytochrome b gene + control region) for most species of the tribe Tragelaphini, including seven bushbuck individuals belonging to the two divergent mtDNA haplogroups, Scriptus and Sylvaticus. Our phylogenetic analyses show that the Scriptus lineage is a sister-group of Sylvaticus in the nuclear tree, whereas it is related to Tragelaphus angasii in the mitochondrial tree. This mito-nuclear discordance indicates that the mitochondrial genome of Scriptus was acquired by introgression after one or several past events of hybridization between bushbuck and an extinct species closely related to T. angasii. The division into two bushbuck species is supported by the analyses of nuclear markers and by the karyotype here described for T. scriptus (2n = 57 M/58F), which is strikingly distinct from the one previously found for T. sylvaticus (2n = 33 M/34F). Molecular dating estimates suggest that the two species separated during the Early Pleistocene after an event of interspecific hybridization, which may have mediated massive chromosomal rearrangements in the common ancestor of T. scriptus.}, } @article {pmid30121081, year = {2018}, author = {Fitzpatrick, CR and Lu-Irving, P and Copeland, J and Guttman, DS and Wang, PW and Baltrus, DA and Dlugosch, KM and Johnson, MTJ}, title = {Chloroplast sequence variation and the efficacy of peptide nucleic acids for blocking host amplification in plant microbiome studies.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {144}, pmid = {30121081}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics ; Chloroplasts/*genetics ; DNA, Bacterial/genetics ; DNA, Chloroplast/*drug effects/genetics ; DNA, Ribosomal/genetics ; Genetic Variation ; Host Specificity ; Nucleic Acid Amplification Techniques ; Peptide Nucleic Acids/*pharmacology ; Phylogeny ; Plant Roots/genetics/microbiology ; Plants/genetics/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The ability to efficiently characterize microbial communities from host individuals can be limited by co-amplification of host organellar sequences (mitochondrial and/or plastid), which share a common ancestor and thus sequence similarity with extant bacterial lineages. One promising approach is the use of sequence-specific peptide nucleic acid (PNA) clamps, which bind to, and block amplification of, host-derived DNA. Universal PNA clamps have been proposed to block host plant-derived mitochondrial (mPNA) and plastid (pPNA) sequences at the V4 16S rRNA locus, but their efficacy across a wide range of host plant species has not been experimentally tested.

RESULTS: Using the universal PNA clamps, we amplified and sequenced root microbial communities from replicate individuals of 32 plant species with a most recent common ancestor inferred at 140 MYA. We found the average rate of host plastid contamination across plant species was 23%, however, particular lineages exhibited much higher rates (62-94%), with the highest levels of contamination occurring in the Asteraceae. We investigated chloroplast sequence variation at the V4 locus across 500 land plant species (Embryophyta) and found six lineages with mismatches between plastid and the universal pPNA sequence, including all species within the Asteraceae. Using a modified pPNA for the Asteraceae sequence, we found (1) host contamination in Asteraceae species was reduced from 65 to 23%; and (2) host contamination in non-Asteraceae species was increased from 12 to 69%. These results demonstrate that even single nucleotide mismatches can lead to drastic reductions in pPNA efficacy in blocking host amplification. Importantly, we found that pPNA type (universal or modified) had no effect on the detection of individual bacterial taxa, or estimates of within and between sample bacterial diversity, suggesting that our modification did not introduce bias against particular bacterial lineages.

CONCLUSIONS: When high similarity exists between host organellar DNA and PCR target sequences, PNA clamps are an important molecular tool to reduce host contamination during amplification. Here, we provide a validated framework to modify universal PNA clamps to accommodate host variation in organellar sequences.}, } @article {pmid30120927, year = {2018}, author = {González, DP and Lamb, HV and Partida, D and Wilson, ZT and Harrison, MC and Prieto, JA and Moresco, JJ and Diedrich, JK and Yates, JR and Olson, SK}, title = {CBD-1 organizes two independent complexes required for eggshell vitelline layer formation and egg activation in C. elegans.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {288-300}, pmid = {30120927}, issn = {1095-564X}, support = {P40 OD010440/OD/NIH HHS/United States ; P41 GM103533/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans ; Caenorhabditis elegans Proteins/*metabolism ; Carrier Proteins/*metabolism ; Egg Shell/*metabolism ; Fertilization ; Membrane Glycoproteins/metabolism ; Oogenesis ; Ovum/metabolism ; Vitelline Membrane/*metabolism ; Zygote/metabolism ; }, abstract = {Metazoan eggs have a specialized coat of extracellular matrix that aids in sperm-egg recognition. The coat is rapidly remodeled after fertilization to prevent polyspermy and establish a more permanent barrier to protect the developing embryo. In nematodes, this coat is called the vitelline layer, which is remodeled into the outermost layer of a rigid and impermeable eggshell. We have identified three key components of the vitelline layer structural scaffold - PERM-2, PERM-4 and CBD-1, the first such proteins to be described in the nematode C. elegans. CBD-1 tethered PERM-2 and PERM-4 to the nascent vitelline layer via two N-terminal chitin-binding domains. After fertilization, all three proteins redistributed from the zygote surface to the outer eggshell. Depletion of PERM-2 and PERM-4 from the scaffold led to a porous vitelline layer that permitted soluble factors to leak through the eggshell and resulted in embryonic death. In addition to its role in vitelline layer assembly, CBD-1 is also known to anchor a protein complex required for fertilization and egg activation (EGG-1-5/CHS-1/MBK-2). We found the PERM complex and EGG complex to be functionally independent, and structurally organized through distinct domains of CBD-1. CBD-1 is thus a multifaceted regulator that promotes distinct aspects of vitelline layer assembly and egg activation. In sum, our findings characterize the first vitelline layer components in nematodes, and provide a foundation through which to explore both conserved and species-specific strategies used by animals to build protective barriers following fertilization.}, } @article {pmid30120791, year = {2018}, author = {Marchini, GL and Arredondo, TM and Cruzan, MB}, title = {Selective differentiation during the colonization and establishment of a newly invasive species.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1689-1703}, doi = {10.1111/jeb.13369}, pmid = {30120791}, issn = {1420-9101}, support = {2005-35320-15317//USDA CSREES/ ; }, abstract = {The potential for rapid evolution in invasive species makes them useful for studying adaptive responses of populations to novel environments. However, phenotypic divergence during invasion is not necessarily due to selection, but may be a product of neutral processes resulting from population bottlenecks during colonization and range expansion. We investigated phenotypic adaptation during the establishment and range expansion of the invasive bunchgrass, slender false brome (Brachypodium sylvaticum; Poaceae). Utilizing a novel approach, we made robust comparisons of functional traits using genetic similarity based on unique alleles to determine the genetic probability of contribution from native source regions and integrated these probabilities into our QST -FST comparisons for 12 physiological and anatomical traits associated with drought stress in the introduced range. Our results indicate phenotypic divergence greater than neutral expectations in five traits between native and invasive populations, indicating selective divergence occurred during invasive species establishment. The results indicate that the majority of divergence in B. sylvaticum occurred after introduction to the novel environment, but prior to invasive range expansion. This study provides evidence for adaptive genetic differentiation during the establishment of an invasive species, while also describing a robust method for the detection of selective processes after species introduction to a novel environment.}, } @article {pmid30120528, year = {2018}, author = {Schaumann, R and Dallacker-Losensky, K and Rosenkranz, C and Genzel, GH and Stîngu, CS and Schellenberger, W and Schulz-Stübner, S and Rodloff, AC and Eschrich, K}, title = {Discrimination of Human Pathogen Clostridium Species Especially of the Heterogeneous C. sporogenes and C. botulinum by MALDI-TOF Mass Spectrometry.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1506-1515}, pmid = {30120528}, issn = {1432-0991}, mesh = {Bacterial Typing Techniques/*methods ; Botulism/*microbiology ; Clostridium/chemistry/classification/*isolation & purification ; Clostridium botulinum/chemistry/classification/*isolation & purification ; Humans ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; Tandem Mass Spectrometry/*methods ; }, abstract = {Clostridium species cause several local and systemic diseases. Conventional identification of these microorganisms is in part laborious, not always reliable, time consuming or does not always distinguish different species, i.e., C. botulinum and C. sporogenes. All in, there is a high interest to find out a reliable, powerful and rapid method to identify Clostridium spp. not only on genus but also on species level. The aim of the present study was to identify Clostridium spp. strains and also to find differences and metabolic groups of C. botulinum by Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). A total of 123 strains of Clostridium spp. (C. botulinum, n = 40, C. difficile, n = 11, C. tetani, n = 11, C. sordellii, n = 20, C. sporogenes, n = 18, C. innocuum, n = 10, C. perfringens, n = 13) were analyzed by MALDI-TOF MS in combination with methods of multivariate statistical analysis. MALDI-TOF MS analysis in combination with methods of multivariate statistical analysis was able to discriminate between the different tested Clostridium spp., even between species which are closely related and difficult to differentiate by traditional methods, i.e., C. sporogenes and C. botulinum. Furthermore, the method was able to separate the different metabolic groups of C. botulinum. Especially, E gene-positive C. botulinum strains are clearly distinguishable from the other species but also from those producing other toxin types. Thus, MALDI-TOF MS represents a reliable and above all quick method for identification of cultivated Clostridium species.}, } @article {pmid30120527, year = {2018}, author = {Chaudhary, DK and Kim, J}, title = {Brevundimonas mongoliensis sp. nov., A Novel Psychrotolerant Bacterium Isolated from Oil-Contaminated Soil.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1530-1536}, pmid = {30120527}, issn = {1432-0991}, support = {2016R1D1A1A09916982//Ministry of Education/ ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; Caulobacteraceae/classification/genetics/*isolation & purification/metabolism ; Cold Temperature ; DNA, Bacterial/genetics ; Environmental Pollution/analysis ; Fatty Acids/chemistry/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Soil/chemistry ; *Soil Microbiology ; }, abstract = {Two yellow-coloured, Gram-stain-negative, motile, and rod-shaped bacteria, designated strains R-10-10T and R-10-15 were isolated from oil-contaminated soil. Both strains were able to grow at 4-40 °C, pH 5.5-10.5, and 0-4% (w/v) NaCl concentration. These strains were taxonomically characterized by a polyphasic approach. Based on the 16S rRNA gene sequence analysis, both strains, R-10-10T and R-10-15, could be affiliated to the genus Brevundimonas and shared highest sequence similarity with Brevundimonas staleyi FWC43T (98.8%), Brevundimonas bullata TK0051T (98.6%), and Brevundimonas subvibrioides CB81T (98.3%). The pairwise sequence similarity between strains R-10-10T and R-10-15 was 99.9%. Both strains R-10-10T and R-10-15 contained phosphatidylglycerol, diphosphatidylglycerol, and four unidentified glycolipids as major polar lipids; ubiquinone-10 as sole respiratory quinone; and summed feature 8 (C18:1ω7c and/or C18:1ω6c), C16:0, summed feature 3 (C16:1ω7c and/or C16:1ω6c), and C18:1ω9c as major fatty acids. The genomic DNA G+C content values of strains R-10-10T and R-10-15 were 67.1 and 66.9 mol%, respectively. The DNA-DNA relatedness between R-10-10T and R-10-15 was higher than 70% but the values were less than 55% with closely related reference type strains. The morphological, physiological, chemotaxonomic, and phylogenetic data clearly distinguished strain R-10-10T from its closest phylogenetic neighbors. Thus, strain R-10-10T is considered to represent a novel species of the genus Brevundimonas, for which the name Brevundimonas mongoliensis sp. nov. is proposed. The type strain is R-10-10T (=KEMB 9005-696T = KACC 19387T = JCM 32172T), and strain R-10-15 is considered as an additional strain of the novel species.}, } @article {pmid30120372, year = {2018}, author = {Galaz, V and Crona, B and Dauriach, A and Jouffray, JB and Österblom, H and Fichtner, J}, title = {Publisher Correction: Tax havens and global environmental degradation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {10}, pages = {1674}, doi = {10.1038/s41559-018-0671-7}, pmid = {30120372}, issn = {2397-334X}, abstract = {An earlier version of the Supplementary Information was mistakenly uploaded when this Perspective was published, and was live until 14 August 2018, when the correct version was uploaded.}, } @article {pmid30120127, year = {2018}, author = {AlRatrout, A and Blunt, MJ and Bijeljic, B}, title = {Wettability in complex porous materials, the mixed-wet state, and its relationship to surface roughness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8901-8906}, pmid = {30120127}, issn = {1091-6490}, abstract = {A quantitative in situ characterization of the impact of surface roughness on wettability in porous media is currently lacking. We use reservoir condition micrometer-resolution X-ray tomography combined with automated methods for the measurement of contact angle, interfacial curvature, and surface roughness to examine fluid/fluid and fluid/solid interfaces inside a porous material. We study oil and water in the pore space of limestone from a giant producing oilfield, acquiring millions of measurements of curvature and contact angle on three millimeter-sized samples. We identify a distinct wetting state with a broad distribution of contact angle at the submillimeter scale with a mix of water-wet and water-repellent regions. Importantly, this state allows both fluid phases to flow simultaneously over a wide range of saturation. We establish that, in media that are largely water wet, the interfacial curvature does not depend on solid surface roughness, quantified as the local deviation from a plane. However, where there has been a significant wettability alteration, rougher surfaces are associated with lower contact angles and higher interfacial curvature. The variation of both contact angle and interfacial curvature increases with the local degree of roughness. We hypothesize that this mixed wettability may also be seen in biological systems to facilitate the simultaneous flow of water and gases; furthermore, wettability-altering agents could be used in both geological systems and material science to design a mixed-wetting state with optimal process performance.}, } @article {pmid30120126, year = {2018}, author = {Warnau, J and Sharma, V and Gamiz-Hernandez, AP and Di Luca, A and Haapanen, O and Vattulainen, I and Wikström, M and Hummer, G and Kaila, VRI}, title = {Redox-coupled quinone dynamics in the respiratory complex I.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8413-E8420}, pmid = {30120126}, issn = {1091-6490}, mesh = {Bacterial Proteins/*chemistry/metabolism ; Benzoquinones/*chemistry/metabolism ; Electron Transport Complex I/*chemistry/metabolism ; Oxidation-Reduction ; Protein Domains ; Thermus thermophilus/*enzymology ; Yarrowia/*enzymology ; }, abstract = {Complex I couples the free energy released from quinone (Q) reduction to pump protons across the biological membrane in the respiratory chains of mitochondria and many bacteria. The Q reduction site is separated by a large distance from the proton-pumping membrane domain. To address the molecular mechanism of this long-range proton-electron coupling, we perform here full atomistic molecular dynamics simulations, free energy calculations, and continuum electrostatics calculations on complex I from Thermus thermophilus We show that the dynamics of Q is redox-state-dependent, and that quinol, QH2, moves out of its reduction site and into a site in the Q tunnel that is occupied by a Q analog in a crystal structure of Yarrowia lipolytica We also identify a second Q-binding site near the opening of the Q tunnel in the membrane domain, where the Q headgroup forms strong interactions with a cluster of aromatic and charged residues, while the Q tail resides in the lipid membrane. We estimate the effective diffusion coefficient of Q in the tunnel, and in turn the characteristic time for Q to reach the active site and for QH2 to escape to the membrane. Our simulations show that Q moves along the Q tunnel in a redox-state-dependent manner, with distinct binding sites formed by conserved residue clusters. The motion of Q to these binding sites is proposed to be coupled to the proton-pumping machinery in complex I.}, } @article {pmid30120125, year = {2018}, author = {Darnell, M and O'Neil, A and Mao, A and Gu, L and Rubin, LL and Mooney, DJ}, title = {Material microenvironmental properties couple to induce distinct transcriptional programs in mammalian stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8368-E8377}, pmid = {30120125}, issn = {1091-6490}, support = {R01 DE013033/DE/NIDCR NIH HHS/United States ; }, mesh = {*Alginates/chemistry/pharmacology ; Animals ; Cell Culture Techniques/*methods ; Cell Differentiation/drug effects ; Glucuronic Acid/chemistry/pharmacology ; Hematopoietic Stem Cells/cytology/*metabolism ; Hexuronic Acids/chemistry/pharmacology ; *Hydrogels/chemistry/pharmacology ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; *Stem Cell Niche ; Transcription, Genetic/*drug effects ; }, abstract = {Variations in a multitude of material microenvironmental properties have been observed across tissues in vivo, and these have profound effects on cell phenotype. Phenomenological experiments have suggested that certain of these features of the physical microenvironment, such as stiffness, could sensitize cells to other features; meanwhile, mechanistic studies have detailed a number of biophysical mechanisms for this sensing. However, the broad molecular consequences of these potentially complex and nonlinear interactions bridging from biophysical sensing to phenotype have not been systematically characterized, limiting the overall understanding and rational deployment of these biophysical cues. Here, we explore these interactions by employing a 3D cell culture system that allows for the independent control of culture substrate stiffness, stress relaxation, and adhesion ligand density to systematically explore the transcriptional programs affected by distinct combinations of biophysical parameters using RNA-seq. In mouse mesenchymal stem cells and human cortical neuron progenitors, we find dramatic coupling among these substrate properties, and that the relative contribution of each property to changes in gene expression varies with cell type. Motivated by the bioinformatic analysis, the stiffness of hydrogels encapsulating mouse mesenchymal stem cells was found to regulate the secretion of a wide range of cytokines, and to accordingly influence hematopoietic stem cell differentiation in a Transwell coculture model. These results give insights into how biophysical features are integrated by cells across distinct tissues and offer strategies to synthetic biologists and bioengineers for designing responses to a cell's biophysical environment.}, } @article {pmid30119990, year = {2018}, author = {Székely, T and Balázsi, G}, title = {Beyond Promoters: How Genes Tweak Their Own Expression.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {10}, pages = {733-735}, doi = {10.1016/j.tig.2018.07.002}, pmid = {30119990}, issn = {0168-9525}, abstract = {The correct expression of genes is vital for cells to function. Schikora-Tamarit et al. show that, in addition to obeying their promoters, most genes can modulate their own expression by either buffering or amplification. This could help to avoid costly overexpression of proteins.}, } @article {pmid30119946, year = {2018}, author = {Stutz, MD and Pellegrini, M}, title = {Mycobacterium tuberculosis: prePPARing and Maintaining the Replicative Niche.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {813-814}, doi = {10.1016/j.tim.2018.08.001}, pmid = {30119946}, issn = {1878-4380}, abstract = {Mycobacterium tuberculosis interferes with the ability of its host cell to undergo apoptosis. Arnett et al. report that the pathogen promotes macrophage survival by engaging the nuclear receptor PPARγ to induce the antiapoptotic protein MCL-1, yielding insights into the pathogenesis of tuberculosis and potentially unlocking new avenues for therapeutic intervention.}, } @article {pmid30119896, year = {2018}, author = {Kikuchi, Y and Nakatsukasa, M and Tsujikawa, H and Nakano, Y and Kunimatsu, Y and Ogihara, N and Shimizu, D and Takano, T and Nakaya, H and Sawada, Y and Ishida, H}, title = {Sexual dimorphism of body size in an African fossil ape, Nacholapithecus kerioi.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {129-140}, doi = {10.1016/j.jhevol.2018.07.003}, pmid = {30119896}, issn = {1095-8606}, abstract = {Sexual size dimorphism in the African fossil ape Proconsul nyanzae (18 million years ago, 18 Ma) has been previously documented. However, additional evidence for sexual dimorphism in Miocene hominoids can provide great insight into the history of extant hominoid mating systems. The present study focused on body mass (BM) sexual dimorphism in Nacholapithecus kerioi from the Middle Miocene (16-15 Ma) in Africa. Bootstrap analysis revealed that P. nyanzae BM sexual dimorphism was lower than that in Pan troglodytes, which exhibits moderate sexual dimorphism, as reported previously. The same simulation revealed that BM sexual dimorphism of N. kerioi was comparable with that in Gorilla spp.; i.e., the males were approximately twice as large as the females. High sexual dimorphism in extant apes is usually indicative of a polygynous social structure (gorilla) or solitary/fission-fusion social system (orangutan). However, because of the high proportion of adult males in this fossil assemblage, the magnitude of dimorphism inferred here cannot be associated with a gorilla-like polygynous or oranguran-like solitary/fission-fusion social structure, and may reflect either taphonomic bias, or some other social structure. Extant hominoids have a long evolutionary history owing to their deep branching, comprising only a few existing members of the original highly successful group. Therefore, it is not surprising that the mating systems of extant hominoids fail to provide fossil apes with a perfect "model". The mating systems of extinct hominoids may have been more diverse than those of extant apes.}, } @article {pmid30119701, year = {2018}, author = {Kebede, A and Gerensea, H and Amare, F and Tesfay, Y and Teklay, G}, title = {The magnitude of anemia and associated factors among pregnant women attending public institutions of Shire Town, Shire, Tigray, Northern Ethiopia, 2018.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {595}, pmid = {30119701}, issn = {1756-0500}, mesh = {Anemia/*epidemiology ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Humans ; Pregnancy ; Pregnancy Complications, Hematologic/*epidemiology ; Prenatal Care ; Prevalence ; Risk Factors ; }, abstract = {OBJECTIVE: Anemia is a widespread health problem among pregnant women causing maternal/infant morbidity and mortality mainly in low-income countries. Understanding of the magnitude of anemia and related socio-demographic variables in a specific setting would help scale-up preventive and therapeutic measures in a locality. So that this study focuses on the magnitude of anemia and its associated factor among pregnant women attending antenatal care in public hospitals of shire town and using institution based cross-sectional study design on 480 randomly selected study subjects.

RESULT: The overall prevalence of anemia was 16.3%. Majority of the participants (52%) have mild anemia (10-10.9 gm/dl). Pregnant mothers with human immunodeficiency virus, intestinal parasitic infection and having lower inter-pregnancy gap were significant predictors of anemia. Preventing infection of the mother during pregnancy and making the gap between pregnancies are necessary.}, } @article {pmid30119696, year = {2018}, author = {Belyhun, Y and Moges, F and Endris, M and Asmare, B and Amare, B and Bekele, D and Tesfaye, S and Alemayehu, M and Biadgelegne, F and Mulu, A and Assefa, Y}, title = {Ocular bacterial infections and antibiotic resistance patterns in patients attending Gondar Teaching Hospital, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {597}, pmid = {30119696}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*pharmacology ; Cross-Sectional Studies ; *Drug Resistance, Bacterial ; Drug Resistance, Multiple, Bacterial ; Escherichia coli/drug effects/isolation & purification ; Escherichia coli Infections/drug therapy ; Ethiopia ; Eye Infections/drug therapy/*microbiology ; Hospitals, Teaching ; Humans ; Microbial Sensitivity Tests ; Prospective Studies ; Staphylococcal Infections/drug therapy ; Staphylococcus aureus/drug effects/isolation & purification ; }, abstract = {OBJECTIVES: Empirical selections of antimicrobial therapy based on clinical observations are common clinical practices in Ethiopia. This study identified common external ocular infections and determined antibiotic susceptibility testing in northwest Ethiopia.

RESULTS: Among 210 patients studied, conjunctivitis 32.9%(69), blepharitis 26.7%(56), dacryocystitis 14.8%(51), blepharoconjunctivitis 11.9%(25), and trauma 10.0%(21) were the most common external ocular infections. Pathogenic bacteria were isolated among 62.4%(131) cases. The distributions of bacteria detected in conjunctivitis, dacryocystitis, and blepharitis patients were 32.8%(43), 23.7%(31), and 16.0%(21), respectively. The most prevalent isolates were coagulase negative Staphylococci; 27.5%(36), S. aureus; 26.7%(35), Pseudomonas species; 10.7%(14), and E. coli; 7.6%(10). Tetracycline, amoxicillin, chloramphenicol, ampicillin, and nalidic acid showed resistance to bacterial isolates with a respective prevalence of 35.9%(47), 32.1%(42), 26.2%(34), 25.2%(33), and 23.7%(31). Multi-drug resistance patterns to the commonly prescribed antibiotics tested was 20.6%(27), 18.3%(24), 17.6%(23), 5.3%(7), and 4.6%(6) to two, three, four, five, and six antibiotics, respectively. Overall, the multi-drug resistance prevalence rate was 66.4%(87). This study confirmed diverse types of external ocular manifestations associated with bacterial infections with wide ranges of antibiotic resistant phenotypes. Thus, combining clinical information, bacteriological analysis, and antimicrobial susceptibility tests are useful for making an evidence-based selection of antibiotics therapy.}, } @article {pmid30119693, year = {2018}, author = {Mangrio, E and Zdravkovic, S and Carlson, E}, title = {A qualitative study of refugee families' experiences of the escape and travel from Syria to Sweden.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {594}, pmid = {30119693}, issn = {1756-0500}, mesh = {Adult ; Aged ; Child ; Emotions ; Family ; Humans ; Middle Aged ; Qualitative Research ; Refugees/*psychology ; Sweden ; Syria/ethnology ; *Violence ; *Warfare ; Young Adult ; }, abstract = {OBJECTIVE: Research shows that, depending on the route of travel during the escape, the journey presents the refugees with different health risks. Traumatic events during flight may have long-lasting physical and psychological effects on the refugee children. Therefore, it is important to illuminate the experiences that refugee families arriving in Sweden have endured during their flight. A qualitative study was conducted through interviews with fifteen recently arrived Syrian refugee families.

RESULTS: The parents described different reasons as to why they as families had to escape the war. Some families had lost jobs and loved ones in the war and did not want their children to die as well. They mentioned that the journeys varied between 10 and 40 days and were usually filled with struggles and threats. The escape to Sweden was expressed as an emotionally trying journey. Many parents talked about the fear and terror the children felt. Traumatic events during the escape, such as separation from family, death of family members, sexual violence, kidnapping or extortion may have long-lasting physical and psychological effects on the refugee children and their families. Therefore, health care workers meeting and caring for these families after arrival must pay close attention to that.}, } @article {pmid30119688, year = {2018}, author = {Zafar, S and Siddiqui, MAR}, title = {Sub-retinal abscess as presenting feature of endogenous Candida endophthalmitis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {598}, pmid = {30119688}, issn = {1756-0500}, mesh = {Abscess ; Adult ; Candida/isolation & purification ; Candidiasis/complications/*diagnosis/therapy ; Endophthalmitis ; Eye Infections, Fungal/complications/*diagnosis/therapy ; Female ; Humans ; Vitrectomy ; }, abstract = {BACKGROUND: Sub-retinal abscess as the presenting feature in the setting of endogenous fungal endophthalmitis is extremely infrequent. Immunodeficiency states are major predisposing risk factors. To the best of our knowledge, this is the first case report of Candida sub-retinal abscess as initial presentation in an immunocompetent patient.

CASE PRESENTATION: A 32-year old, generally fit and well, female presented to us with gradually deteriorating vision in her right eye. Visual acuity was counting fingers in the right eye and, 20/30 in the left eye. Right eye fundus examination showed a full thickness, yellowish-white foveal lesion, and significant vitreous haze. Left eye examination was normal. Upon direct questioning, the patient disclosed history of backstreet abortion 3 weeks prior to the onset of her ocular symptoms. She underwent vitreous tap and intravitreal antibiotics (amphotericin B, 5 μg/0.5 ml). Vitreous culture showed profuse growth of Candida albicans. Because her condition was progressively deteriorating, she underwent 25 g vitrectomy plus repeat intravitreal amphotericin B under general anaesthesia. Three weeks post-vitrectomy, vitreous inflammation resolved completely, and the sub-retinal abscess healed with a macular scar formation. Over a follow-up of 4 years, no recurrences were observed.

CONCLUSION: Our case highlights the importance of considering Candida albicans infection in the differential diagnosis of sub-retinal abscesses. Although immunocompromised states are traditionally identified as predisposing factors for fungal infections, fungal endogenous endophthalmitis can occur in healthy individuals as well.}, } @article {pmid30119679, year = {2018}, author = {Shlamkovich, T and Aharon, L and Koslawsky, D and Einav, Y and Papo, N}, title = {Targeting the Tie2-αvβ3 integrin axis with bi-specific reagents for the inhibition of angiogenesis.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {92}, pmid = {30119679}, issn = {1741-7007}, abstract = {BACKGROUND: Increased activity of the receptor tyrosine kinase Tie2 has been implicated in the promotion of pathological angiogenesis. This activity is mainly mediated through angiopoietin (Ang)1- and Ang2-dependent activation of integrins by Tie2, rendering the Ang/Tie2/integrin axis an attractive putative target for cancer therapeutics.

RESULTS: To target this axis, we developed single domain, non-immunoglobulin high-affinity bi-specific protein inhibitors against both Tie2 and αvβ3 integrin. We have previously engineered the Ang2-binding domain of Tie2 (Ang2-BD) as a Tie2 inhibitor. Here, we engineered an exposed loop in Ang2-BD to generate variants that include an integrin-binding Arg-Gly-Asp (RGD) motif and used flow cytometry screening of a yeast-displayed Ang2-BD RGD loop library to identify the integrin antagonists. The bi-specific antagonists targeting both Tie2 and αvβ3 integrin inhibited adhesion and proliferation of endothelial cells cultured together with the αvβ3 integrin ligand vitronectin, as well as endothelial cell invasion and tube formation. The bi-specific reagents inhibited downstream signaling by Tie2 intracellularly in response to its agonist Ang1 more effectively than the wild-type Ang2 BD that binds Tie2 alone.

CONCLUSIONS: Collectively, this study-the first to describe inhibitors targeting all the known functions resulting from Tie2/integrin αvβ3 cross-talk-has created new tools for studying Tie2- and integrin αvβ3-dependent molecular pathways and provides the basis for the rational and combinatorial engineering of ligand-Tie2 and ligand-integrin αvβ3 receptor interactions. Given the roles of these pathways in cancer angiogenesis and metastasis, this proof of principle study paves the route to create novel Tie2/integrin αvβ3-targeting proteins for clinical use as imaging and therapeutic agents.}, } @article {pmid30119658, year = {2018}, author = {Gu, T and Lu, L and Wang, J and Tian, L and Wei, W and Wu, X and Xu, Q and Chen, G}, title = {The NOD1 and NOD2 in mandarinfish (Siniperca chuatsi): molecular characterization, tissue distribution, and expression analysis.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {61}, pmid = {30119658}, issn = {1471-2156}, support = {2011-137//The Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, abstract = {BACKGROUND: NOD-like receptors (NLRs) are a family of cytoplasmic pattern recognition receptors (PRRs), of which NOD1 and NOD2, are the main representative members. Many investigations have focused on the role of NOD1 and NOD2 in the innate immune response in Cypriniformes and Siluriformes. As an important economic fish in Perciformes, little is known about the function of NOD1 and NOD2 in mandarinfish (Siniperca chuatsi).

RESULTS: The full-length NOD1 and NOD2 cDNA sequence was obtained using reverse transcription polymerase chain reaction (RT-PCR) and rapid amplification of cDNA ends (RACE). The mandarinfish NOD1 and NOD2 cDNA sequences contain 3247 bp and 3257 bp, and encode 918 amino acids and 988 amino acids, respectively. Multiple sequence alignments showed that mNOD1 and mNOD2 share high similarity with that from other vertebrates. RT-PCR analysis revealed that relatively high levels of mNOD1 and mNOD2 mRNA were detected in gill and head kidney tissues, compared with the heart, spleen, liver, muscle, and intestine. In addition, the relative levels of mNOD1 and mNOD2 transcripts were significantly upregulated in three tissues when the fishes were challenged with LPS and Poly I:C, interestingly, the NOD1 mRNA got peaked earlier than NOD2 after LPS induction in the spleen, gill, and head kidney, and during Poly I:C treatment, the NOD2 mRNA got peaked at 8 h in spleen and gill, while NOD1 showed significant higher expression at 24 h post infection, besides, in head kidney, the NOD2 mRNA showed a great increasing trend and NOD1 got peaked at 16 h. Therefore the mNOD1 and mNOD2 may act differently within different tissues in different time during antiviral and antibacterial defense.

CONCLUSIONS: These results revealed the dynamic mNOD1 and mNOD2 expression during viral and bacterial infections, which suggested the NOD1 and NOD2 play important roles in innate immune of mandarinfish.}, } @article {pmid30119655, year = {2018}, author = {Wen, G and Deng, S and Song, W and Jin, H and Xu, J and Liu, X and Xie, R and Song, P and Tuo, B}, title = {Helicobacter pylori infection downregulates duodenal CFTR and SLC26A6 expressions through TGFβ signaling pathway.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {87}, pmid = {30119655}, issn = {1471-2180}, abstract = {BACKGROUND: The pathogenesis of Helicobacter pylori (H. pylori) infection-induced duodenal ulcer remains to be elucidated. Duodenal mucosal bicarbonate secretion is the most important protective factor against acid-induced mucosal injury. We previously revealed that H. pylori infection downregulated the expression and functional activity of duodenal mucosal cystic fibrosis transmembrane conductance regulator (CFTR) and solute linked carrier 26 gene family A6 (SLC26A6) which are the two key duodenal mucosal epithelial cellular bicarbonate transporters to mediate duodenal bicarbonate secretion. In this study, we investigated the mechanism of H. pylori infection-induced duodenal CFTR and SLC26A6 expression downregulation.

RESULTS: We found that H. pylori infection induced the increase of serum transforming growth factor β (TGFβ) level and duodenal mucosal TGFβ expression and the decrease of duodenal mucosal CFTR and SLC26A6 expressions in C57 BL/6 mice. The results from the experiments of human duodenal epithelial cells (SCBN) showed that H. pylori increased TGFβ production and decreased CFTR and SLC26A6 expressions in SCBN cells. TGFβ inhibitor SB431542 reversed the H. pylori-induced CFTR and SLC26A6 expression decreases. The further results showed that TGFβ directly decreased CFTR and SLC26A6 expressions in SCBN cells. TGFβ induced the phosphorylation of p38 mitogen-activated protein kinase (MAPK) and P38 MAPK inhibitor SB203580 reversed the TGFβ-induced CFTR and SLC26A6 expression decreases.

CONCLUSIONS: H. pylori infection downregulates duodenal epithelial cellular CFTR and SLC26A6 expressions through TGFβ-mediated P38 MAPK signaling pathway, which contributes to further elucidating the pathogenesis of H. pylori-associated duodenal ulcer.}, } @article {pmid30119648, year = {2018}, author = {Morka, K and Bystroń, J and Bania, J and Korzeniowska-Kowal, A and Korzekwa, K and Guz-Regner, K and Bugla-Płoskońska, G}, title = {Identification of Yersinia enterocolitica isolates from humans, pigs and wild boars by MALDI TOF MS.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {86}, pmid = {30119648}, issn = {1471-2180}, abstract = {BACKGROUND: Yersinia enterocolitica is widespread within the humans, pigs and wild boars. The low isolation rate of Y. enterocolitica from food or environmental and clinical samples may be caused by limited sensitivity of culture methods. The main goal of present study was identification of presumptive Y. enterocolitica isolates using MALDI TOF MS. The identification of isolates may be difficult due to variability of bacterial strains in terms of biochemical characteristics. This work emphasizes the necessity of use of multiple methods for zoonotic Y. enterocolitica identification.

RESULTS: Identification of Y. enterocolitica isolates was based on MALDI TOF MS, and verified by VITEK® 2 Compact and PCR. There were no discrepancies in identification of all human' and pig' isolates using MALDI TOF MS and VITEK® 2 Compact. However three isolates from wild boars were not decisively confirmed as Y. enterocolitica. MALDI TOF MS has identified the wild boar' isolates designated as 3dz, 4dz, 8dz as Y. enterocolitica with a high score of matching with the reference spectra of MALDI Biotyper. In turn, VITEK® 2 Compact identified 3dz and 8dz as Y. kristensenii, and isolate 4dz as Y. enterocolitica. The PCR for Y. enterocolitica 16S rDNA for these three isolates was negative, but the 16S rDNA sequence analysis identified these isolates as Y. kristensenii (3dz, 4dz) and Y. pekkanenii (8dz). The wild boar' isolates 3dz, 4dz and 8dz could not be classified using biotyping. The main bioserotype present within pigs and human faeces was 4/O:3. It has been shown that Y. enterocolitica 1B/O:8 can be isolated from human faeces using ITC/CIN culturing.

CONCLUSION: The results of our study indicate wild boars as a reservoir of new and atypical strains of Yersinia, for which protein and biochemical profiles are not included in the MALDI Biotyper or VITEK® 2 Compact databases. Pigs in the south-west Poland are the reservoir for pathogenic Y. enterocolitica strains. Four biochemical features included in VITEK® 2 Compact known to be common with Wauters scheme were shown to produce incompatible results, thus VITEK® 2 Compact cannot be applied in biotyping of Y. enterocolitica.}, } @article {pmid30119646, year = {2018}, author = {Taratummarat, S and Sangphech, N and Vu, CTB and Palaga, T and Ondee, T and Surawut, S and Sereemaspun, A and Ritprajak, P and Leelahavanichkul, A}, title = {Gold nanoparticles attenuates bacterial sepsis in cecal ligation and puncture mouse model through the induction of M2 macrophage polarization.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {85}, pmid = {30119646}, issn = {1471-2180}, abstract = {BACKGROUND: Gold nanoparticles (AuNP) have several biochemical advantageous properties especially for a candidate of drug carrier. However, the non-conjugated AuNP has a higher rate of cellular uptake than the conjugated ones. Spherical AuNP in a proper size (20-30 nm) is non-toxic to mice and shows anti-inflammatory properties. We tested if the administration of AuNP, as an adjuvant to antibiotics, could attenuate bacterial sepsis in cecal ligation and puncture (CLP) mouse model with antibiotic (imipenem/cilastatin).

RESULTS: Indeed, AuNP administration at the time of CLP improved the survival, blood bacterial burdens, kidney function, liver injury and inflammatory cytokines (TNF-α, IL-6, IL-1β and IL-10). AuNP also decreased M1 macrophages (CD86 + ve in F4/80 + ve cells) and increased M2 macrophages (CD206 + ve in F4/80 + ve cells) in the spleens of sepsis mice. The weak antibiotic effect of AuNP was demonstrated as the reduction of E. coli colony after 4 h incubation. In addition, AuNP altered cytokine production of bone-marrow-derived macrophages including reduced TNF-α, IL-6 and IL-1β but increased IL-10 at 6 and 24 h. Moreover, AuNP induced macrophage polarization toward anti-inflammatory responses (M2) as presented by increased Arg1 (Arginase 1) and PPARγ with decreased Nos2 (inducible nitric oxide synthase, iNos) and Nur77 at 3 h after incubation in vitro.

CONCLUSIONS: The adjuvant therapy of AuNP, with a proper antibiotic, attenuated CLP-induced bacterial sepsis in mice, at least in part, through the antibiotic effect and the induction of macrophage function toward the anti-inflammatory responses.}, } @article {pmid30119641, year = {2018}, author = {van Mastrigt, O and Di Stefano, E and Hartono, S and Abee, T and Smid, EJ}, title = {Large plasmidome of dairy Lactococcus lactis subsp. lactis biovar diacetylactis FM03P encodes technological functions and appears highly unstable.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {620}, pmid = {30119641}, issn = {1471-2164}, mesh = {DNA Replication/genetics ; DNA, Bacterial/genetics ; Dairy Products/*microbiology ; Dairying/*methods ; Drug Resistance, Microbial/genetics ; *Genome, Bacterial ; *Genomic Instability ; Interspersed Repetitive Sequences/genetics ; Lactococcus lactis/*genetics/growth & development ; Plasmids/*genetics/physiology ; }, abstract = {BACKGROUND: Important industrial traits have been linked to plasmids in Lactococcus lactis.

RESULTS: The dairy isolate L. lactis subsp. lactis biovar diacetylactis FM03P was sequenced revealing the biggest plasmidome of all completely sequenced and published L. lactis strains up till now. The 12 plasmids that were identified are: pLd1 (8277 bp), pLd2 (15,218 bp), pLd3 (4242 bp), pLd4 (12,005 bp), pLd5 (7521 bp), pLd6 (3363 bp), pLd7 (30,274 bp), pLd8 (47,015 bp), pLd9 (15,313 bp), pLd10 (39,563 bp), pLd11 (9833 bp) and pLd12 (3321 bp). Structural analysis of the repB promoters and the RepB proteins showed that eleven of the plasmids replicate via the theta-type mechanism, while only plasmid pLd3 replicates via a rolling-circle replication mechanism. Plasmids pLd2, pLd7 and pLd10 contain a highly similar operon involved in mobilisation of the plasmids. Examination of the twelve plasmids of L. lactis FM03P showed that 10 of the plasmids carry putative genes known to be important for growth and survival in the dairy environment. These genes encode technological functions such as lactose utilisation (lacR-lacABCDFEGX), citrate uptake (citQRP), peptide degradation (pepO and pepE) and oligopeptide uptake (oppDFBCA), uptake of magnesium and manganese (2 mntH, corA), exopolysaccharides production (eps operon), bacteriophage resistance (1 hsdM, 1 hsdR and 7 different hsdS genes of a type I restriction-modification system, an operon of three genes encoding a putative type II restriction-modification system and an abortive infection gene) and stress resistance (2 uspA, cspC and cadCA). Acquisition of these plasmids most likely facilitated the adaptation of the recipient strain to the dairy environment. Some plasmids were already lost during a single propagation step signifying their instability in the absence of a selective pressure.

CONCLUSIONS: Lactococcus lactis FM03P carries 12 plasmids important for its adaptation to the dairy environment. Some of the plasmids were easily lost demonstrating that propagation outside the dairy environment should be minimised when studying dairy isolates of L. lactis.}, } @article {pmid30119622, year = {2018}, author = {Gomez-Raya, L and Silio, L and Rauw, WM and Gracia-Cortés, LA and Rodríguez, C}, title = {Extent of third-order linkage disequilibrium in a composite line of Iberian pigs.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {60}, pmid = {30119622}, issn = {1471-2156}, support = {AGL2016-75942-R//Spanish Programa Nacional de Proyectos de Investigación Fundamental/ ; ERA-NET SUSPIG//European Union/ ; }, abstract = {BACKGROUND: Previous studies on linkage disequilibrium have investigated second order linkage disequilibrium in animal and plant populations. The objective of this paper was to investigate the genome-wide levels of third order linkage disequilibrium in a composite line founded by admixture of four Iberian pig strains. A model for the generation of third order linkage disequilibrium by population admixture is proposed. A computer Expectation-Maximization algorithm is developed and applied to the estimation of third order linkage disequilibrium at inter- and intra-chromosomal level using 26,347 SNPs typed in 306 sows. The relationship of third order linkage disequilibrium with physical distance was investigated over 35 million triplets in SSC12. Basic and normalized estimates of inter and intra-chromosomal third order linkage disequilibrium are reported.

RESULTS: Genome-wide analyses revealed that third order linkage disequilibrium is rather common among linked loci in this Iberian pig line. It is shown that population admixture of multiple populations may explain the observed levels of third order linkage disequilibrium although it could be generated by genetic drift. Third order linkage disequilibrium decreases rapidly up to 4 Mb and then declines slowly. The short distances between consecutive markers explain the maintenance of the observed third order linkage disequilibria levels when using a model incorporating the break-up of disequilibrium by recombination. Genome-wide testing also revealed that only 3.6% of the normalized estimates were different from 1, - 1, 0, or from a not well-defined situation in which there is only one possible value for the third order linkage disequilibrium parameter, given allele frequencies and pairwise linkage disequilibria parameters.

CONCLUSIONS: Third order linkage disequilibrium is common among linked markers in the analyzed pig line and may have been generated by population admixture of multiple populations or by genetic drift. As with second order linkage disequilibrium, the absolute value of the third order linkage disequilibrium decreases with physical distance. Normalization of third order linkage disequilibrium should be avoided for closely linked bi-allelic loci.}, } @article {pmid30118662, year = {2018}, author = {Lopez, EW and Vue, Z and Broaddus, RR and Behringer, RR and Gladden, AB}, title = {The ERM family member Merlin is required for endometrial gland morphogenesis.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {301-314}, doi = {10.1016/j.ydbio.2018.08.006}, pmid = {30118662}, issn = {1095-564X}, support = {R25 GM056929/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Adhesion/physiology ; Cell Polarity/physiology ; DNA-Binding Proteins/metabolism/physiology ; Endometrium/cytology/*growth & development/metabolism/pathology ; Epithelial Cells/metabolism ; Female ; In Situ Hybridization ; Infertility, Female ; Mice ; Mice, Inbred C57BL ; Morphogenesis/physiology ; Neurofibromin 2/deficiency/genetics/metabolism/*physiology ; Signal Transduction ; Transcription Factors/metabolism/physiology ; }, abstract = {Disruption of endometrial gland formation or function can cause female infertility. Formation of endometrial glands via tubulogenesis of luminal epithelial cells requires the establishment and maintenance of cell polarity and cell adhesion. The FERM domain-containing protein Merlin coordinates epithelial cell polarity and cell adhesion and is critical for epithelial tissue function in the skin and kidney. We now demonstrate a requirement for Merlin in endometrial gland development. Conditional deletion of Merlin in the endometrium results in female infertility caused by the absence of gland formation. Interestingly, we observed glandular epithelial markers within discrete groups of cells in the Merlin-deficient luminal epithelium. Wnt signaling, a pathway necessary for endometrial gland development is maintained in Merlin-deficient endometrium, suggesting the glandular fate program is active. Instead, we observe increased levels of apical actin and markers indicative of high membrane tension on the basal surface of the Merlin-deficient luminal epithelium. These findings suggest that the structural integrity of the luminal epithelium during gland formation is required for appropriate endometrial tubulogenesis and tissue function. Moreover, our work implicates Merlin-dependent regulation of mechanical tension in the proper formation of endometrial gland architecture and function.}, } @article {pmid30117801, year = {2018}, author = {Wang, G and Xu, S and Su, H and Chen, B and Huang, W and Liang, J and Wang, Y and Yu, K}, title = {Motiliproteus coralliicola sp. nov., a bacterium isolated from coral.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3292-3295}, doi = {10.1099/ijsem.0.002984}, pmid = {30117801}, issn = {1466-5034}, mesh = {Animals ; Anthozoa/*microbiology ; Bacteria/genetics ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Islands ; Oceanospirillaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-negative, non-spore-forming, aerobic, motile, ovoid or rod-shaped bacterium, designated strain C34T, was isolated from a Porites species coral on Weizhou Island, China. Optimal growth occurred in 4 % NaCl (w/v), at 30 °C and pH 8. The only detected respiratory quinone was Q-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified ninhydrin-positive lipids, one ninhydrin-positive unidentified phospholipid and two unidentified polar lipids. The genome DNA G+C content was 56.7 mol%. The major cellular fatty acids were C16 : 1ω7c/iso-C15 : 0 2-OH, C16 : 0, C18 : 1ω7c/ω6c, C18 : 0 and iso-C11 : 0 3-OH. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain C34T forms a stable cluster with Motiliproteus sediminis CICC 10858T (with the highest sequence similarity of 95.7 %). Strain C34T was also physiologically and chemical taxonomically similar to M. sediminis CICC 10858T, although they could be distinguished by colony colour on 2216E agar, the flagellum position and the diphosphatidylglycerol content in the cellular polar lipid. Thus, strain C34T is suggested to represent a new species in the genus Motiliproteus, for which the name Motiliproteus coralliicola is proposed. The type strain is C34T (=MCCC 1K03462T=KCTC 62319T).}, } @article {pmid30117800, year = {2018}, author = {Kim, JS and Choe, H and Kim, KM and Lee, YR and Rhee, MS and Park, DS}, title = {Lactobacillus porci sp. nov., isolated from small intestine of a swine.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3118-3124}, doi = {10.1099/ijsem.0.002949}, pmid = {30117800}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; DNA-Directed RNA Polymerases/genetics ; Fatty Acids/chemistry ; Fermentation ; Genes, Bacterial ; Intestine, Small/*microbiology ; Lactic Acid/chemistry ; Lactobacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Swine/*microbiology ; }, abstract = {A facultatively anaerobic, Gram-stain-positive, catalase-negative, rod-shaped lactic acid bacterium, designated SG816T, was isolated from small intestine of a swine. Optimal growth occurred at 37 °C and pH 7.0. Furthermore, growth occurred in NaCl up to 0.5 % (w/v) but not at levels of salinity higher than 1 %. Comparative 16S rRNA gene sequencing and the matrix-associated laser desorption/ionization-time-of-flight mass spectometry profiling showed that strain SG816T was closely related to Lactobacillus delbrueckiisubsp. bulgaricus KCTC 3635T (95.9 %) and Lactobacillus delbrueckiisubsp. indicus JCM 15610T (95.9 %), followed by other Lactobacillus delbrueckii subspecies (95.9-95.7 %) and Lactobacillus equicursoris DSM 19284T (95.6 %). A comparison of two housekeeping genes, RNA polymerase alpha subunit (rpoA) and phenylalanyl-tRNA synthase alpha subunit (pheS), revealed that strain SG816T formed a separate branch within the clade of the genus Lactobacillus. The DNA G+C content level of the strain SG816T was 51.5 mol%. The strain was homofermentative and produced d-lactic acid from glucose fermentation. The major cellular fatty acids (>10 %) of the isolate were C18 : 1ω9c and C16 : 0. The peptidoglycan type was A4α l-Lys-d-Asp. On the basis of distinct phenotypic and phylogenetic properties, strain SG816T represents a novel species of the genus Lactobacillus, for which the name Lactobacillus porci sp. nov. is proposed. The type strain is SG816T (=KCTC 21090T=NBRC 112917T).}, } @article {pmid30117799, year = {2018}, author = {Hu, Y and Feng, Y and Qin, J and Radolfova-Krizova, L and Maixnerova, M and Zhang, X and Nemec, A and Zong, Z}, title = {Acinetobacter wuhouensis sp. nov., isolated from hospital sewage.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3212-3216}, doi = {10.1099/ijsem.0.002963}, pmid = {30117799}, issn = {1466-5034}, mesh = {Acinetobacter/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Hospitals ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {We recovered eight strains of the genus Acinetobacter from hospital sewage at West China Hospital in Chengdu, China. Based on the comparative analysis of the rpoB sequence, these strains formed a strongly supported and internally coherent cluster (intra-cluster identity of ≥98.0 %), which was clearly separated from all known Acinetobacter species (≤91.1 %). The eight strains also formed a tight and distinct cluster based on the genus-wide comparison of whole-cell mass fingerprints generated by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. In addition, the combination of their ability to assimilate 2,3-butanediol and phenylacetate, but not 4-hydroxybenzoate, and the inability to grow at 37 °C could distinguish these eight strains from all known Acinetobacter species. Whole-genomic sequencing has been performed for two selected strains, WCHA60T and WCHA62. There were 96.65 % average nucleotide identity (ANI) and 72 % in silico DNA-DNA hybridization (isDDH) values between WCHA60T and WCHA62, suggesting that the two strains indeed belonged to the same species. In contrast, the ANI and isDDH values between the two strains and the known Acinetobacter species were <83 and <30 %, respectively; both of which were far below the cut-off to define a bacterial species. Therefore, the eight strains should be considered to represent a novel species of the genus Acinetobacter, for which the name Acinetobacterwuhouensis sp. nov. is proposed. The type strain is WCHA60T (=CCTCC AB 2016204T=GDMCC 1.1100T=KCTC 52505T).}, } @article {pmid30117501, year = {2018}, author = {Waltemath, D and Bergmann, FT and Chaouiya, C and Czauderna, T and Gleeson, P and Goble, C and Golebiewski, M and Hucka, M and Juty, N and Krebs, O and Le Novère, N and Mi, H and Moraru, II and Myers, CJ and Nickerson, D and Olivier, BG and Rodriguez, N and Schreiber, F and Smith, L and Zhang, F and Bonnet, E}, title = {Correction to: Meeting report from the fourth meeting of the Computational Modeling in Biology Network (COMBINE).}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {17}, doi = {10.1186/s40793-018-0320-4}, pmid = {30117501}, issn = {1944-3277}, abstract = {[This corrects the article DOI: 10.4056/sigs.5279417.].}, } @article {pmid30117262, year = {2018}, author = {Marchant, HK and Tegetmeyer, HE and Ahmerkamp, S and Holtappels, M and Lavik, G and Graf, J and Schreiber, F and Mussmann, M and Strous, M and Kuypers, MMM}, title = {Metabolic specialization of denitrifiers in permeable sediments controls N2 O emissions.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4486-4502}, doi = {10.1111/1462-2920.14385}, pmid = {30117262}, issn = {1462-2920}, abstract = {Coastal oceans receive large amounts of anthropogenic fixed nitrogen (N), most of which is denitrified in the sediment before reaching the open ocean. Sandy sediments, which are common in coastal regions, seem to play an important role in catalysing this N-loss. Permeable sediments are characterized by advective porewater transport, which supplies high fluxes of organic matter into the sediment, but also leads to fluctuations in oxygen and nitrate concentrations. Little is known about how the denitrifying communities in these sediments are adapted to such fluctuations. Our combined results indicate that denitrification in eutrophied sandy sediments from the world's largest tidal flat system, the Wadden Sea, is carried out by different groups of microorganisms. This segregation leads to the formation of N2 O which is advectively transported to the overlying waters and thereby emitted to the atmosphere. At the same time, the production of N2 O within the sediment supports a subset of Flavobacteriia which appear to be specialized on N2 O reduction. If the mechanisms shown here are active in other coastal zones, then denitrification in eutrophied sandy sediments may substantially contribute to current marine N2 O emissions.}, } @article {pmid30117257, year = {2018}, author = {Wang, L and Zhang, S and Li, JH and Zhang, YJ}, title = {Mitochondrial genome, comparative analysis and evolutionary insights into the entomopathogenic fungus Hirsutella thompsonii.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3393-3405}, doi = {10.1111/1462-2920.14379}, pmid = {30117257}, issn = {1462-2920}, support = {201601D011065//Natural Science Foundation of Shanxi Province/ ; }, abstract = {Nuclear genomes of two isolates of Hirsutella thompsonii, a pathogen causing epizootics among mites, have been reported; in contrast, its mitochondrial genome (mitogenome) has remained unknown, limiting our understanding of its evolution. Herein, we annotated the first complete mitogenome of H. thompsonii, which encoded all standard fungal mitochondrial genes plus three free-standing ORFs. Transcriptional analyses validated the expression of most conserved genes and revealed some interesting transcription patterns of mitochondrial genes. Phylogenetic analyses confirmed its placement in Ophiocordycipitaceae. Comparison of five different isolates originally collected from different locations revealed mitogenome size variations (60.3-66.4 kb) mainly due to different numbers of introns. A total of 15 intron loci were identified, with 11 existing in all 5 isolates and 4 showing presence/absence dynamics. These introns were most likely obtained through horizontal transfer from other fungal organisms. Those common introns might have been in H. thompsonii mitogenomes since the divergence of the fungus from its putative sister species H. minnesotensis, whereas those dynamic introns might have experienced 1-2 gain or loss events. We also detected evidence of degeneration for some introns. Overall, our study shed new insights into the mitochondrial evolution of the acaropathogenic fungus H. thompsonii.}, } @article {pmid30117256, year = {2018}, author = {Li, G and Gao, P and Zhi, B and Fu, B and Gao, G and Chen, Z and Gao, M and Wu, M and Ma, T}, title = {The relative abundance of alkane-degrading bacteria oscillated similarly to a sinusoidal curve in an artificial ecosystem model from oil-well products.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3772-3783}, doi = {10.1111/1462-2920.14382}, pmid = {30117256}, issn = {1462-2920}, support = {41773080//National Natural Science Foundation of China/ ; 14ZCZDSY00016//Tianjin Research Program of Application Foundation and Advanced Technology/ ; 16JCYBJC23700//Tianjin Research Program of Application Foundation and Advanced Technology/ ; 16JCZDJC32000//Tianjin Research Program of Application Foundation and Advanced Technology/ ; }, abstract = {Microbial phylogenetic diversity and species interactions in natural ecosystems have been investigated extensively, but our knowledge about their ecological roles, community dynamics and succession patterns is far from complete. This knowledge is essential to understand the complicated interactions of microorganisms in natural ecosystems. Here, an artificial ecosystem model of microorganisms was constructed from oil-well products and cultivated in a chemostat to investigate the succession pattern of alkane-degrading bacteria, a functional population in oil reservoirs. Their abundance was quantified by an improved qPCR technique. Our results showed that the phylogenetic structure of this artificial ecosystem model is stable during most of the chemostat cultivation process, while the genotype structure of alkane-degrading bacteria containing alkB genes shifted and their relative abundance oscillated similarly to a sinusoidal curve, like the succession pattern of producers in the Lotka-Volterra model. These results suggest that some theoretical frameworks of macroecology may work well in microbial ecosystems and be an efficient tool to understand them.}, } @article {pmid30117254, year = {2018}, author = {Savvichev, AS and Babenko, VV and Lunina, ON and Letarova, MA and Boldyreva, DI and Veslopolova, EF and Demidenko, NA and Kokryatskaya, NM and Krasnova, ED and Gaisin, VA and Kostryukova, ES and Gorlenko, VM and Letarov, AV}, title = {Sharp water column stratification with an extremely dense microbial population in a small meromictic lake, Trekhtzvetnoe.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3784-3797}, doi = {10.1111/1462-2920.14384}, pmid = {30117254}, issn = {1462-2920}, support = {0104-2014-0101//Russian Federal Agency of Scientific Organisations/ ; 0104-2014-0109//Russian Federal Agency of Scientific Organisations/ ; 16-14-10201//Russian Science Foundation/ ; 17-04-01263//RFBR/ ; }, abstract = {Located on the shore of Kandalaksha Bay (the White Sea, Russia) and previously separated from it, Trekhtzvetnoe Lake (average depth 3.5 m) is one of the shallowest meromictic lakes known. Despite its shallowness, it features completely developed water column stratification with high-density microbial chemocline community (bacterial plate) and high rates of major biogeochemical processes. A sharp halocline stabilizes the stratification. Chlorobium phaeovibrioides dominated the bacterial plate, which reached a density of 2 × 108 cell ml-1 and almost completely intercepts H2 S diffusion from the anoxic monimolimnion. The resulting anoxygenic photosynthesis rate reached 240 μmol C l-1 day-1 , exceeding the oxygenic photosynthesis rate in the mixolimnion. The rates of other processes are also high, reaching 4.5 μmol CH4 l-1 day-1 for methane oxidation and 35 μmol S l-1 day-1 for sulfate reduction. Metagenomic analysis demonstrated that the Chl. phaeovibrioides population in the bacterial plate layer had nearly clonal homogeneity, although some fraction of these cells harbour a plasmid. The Chlorobium population was associated with bacteriophages that share homology with CRISPR spacers in the host. These features make the ecosystem of the Trekhtzvetnoe Lake a valuable model for studying regulation and evolution processes in natural high-density microbial systems.}, } @article {pmid30117250, year = {2018}, author = {Cabello-Yeves, PJ and Picazo, A and Camacho, A and Callieri, C and Rosselli, R and Roda-Garcia, JJ and Coutinho, FH and Rodriguez-Valera, F}, title = {Ecological and genomic features of two widespread freshwater picocyanobacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3757-3771}, doi = {10.1111/1462-2920.14377}, pmid = {30117250}, issn = {1462-2920}, support = {//FEDER funds/ ; //Generalitat Valenciana/ ; CGL2015-69557-R'//CLIMAWET/ ; //Spanish Ministry of Economy and Competitiveness/ ; //European Fund for Regional Development/ ; }, abstract = {We present two genomes of widespread freshwater picocyanobacteria isolated by extinction dilution from a Spanish oligotrophic reservoir. Based on microscopy and genomic properties, both picocyanobacteria were tentatively designated Synechococcus lacustris Tous, formerly described as a metagenome assembled genome (MAG) from the same habitat, and Cyanobium usitatum Tous, described here for the first time. Both strains were purified in unicyanobacterial cultures, and their genomes were sequenced. They are broadly distributed in freshwater systems; the first seems to be a specialist on temperate reservoirs (Tous, Amadorio, Dexter, Lake Lanier, Sparkling), and the second appears to also be abundant in cold environments including ice-covered lakes such as Lake Baikal, Lake Erie or the brackish Baltic Sea. Having complete genomes provided access to the flexible genome that does not assemble in MAGs. We found several genomic islands in both genomes, within which there were genes for nitrogen acquisition, transporters for a wide set of compounds and biosynthesis of phycobilisomes in both strains. Some of these regions of low coverage in metagenomes also included antimicrobial compounds, transposases and phage defence systems, including a novel type III CRISPR-Cas phage defence system that was only detected in Synechococcus lacustris Tous.}, } @article {pmid30117243, year = {2018}, author = {Cohen, NR and Gong, W and Moran, DM and McIlvin, MR and Saito, MA and Marchetti, A}, title = {Transcriptomic and proteomic responses of the oceanic diatom Pseudo-nitzschia granii to iron limitation.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3109-3126}, doi = {10.1111/1462-2920.14386}, pmid = {30117243}, issn = {1462-2920}, support = {3782//Gordon and Betty Moore Foundation/ ; OCE1334935//National Science Foundation/ ; 544236//Simons Foundation/SFARI/ ; 3782//Gordon Betty Moore Foundation/ ; }, abstract = {Diatoms are a highly successful group of photosynthetic protists that often thrive under adverse environmental conditions. Members of the genus Pseudo-nitzschia are ecologically important diatoms which are able to subsist during periods of chronic iron limitation and form dense blooms following iron fertilization events. The cellular strategies within diatoms that orchestrate these physiological responses to variable iron concentrations remain largely uncharacterized. Using a combined transcriptomic and proteomic approach, we explore the exceptional ability of a diatom isolated from the iron-limited Northeast Pacific Ocean to reorganize its intracellular processes as a function of iron. We compared the molecular responses of Pseudo-nitzschia granii observed under iron-replete and iron-limited growth conditions to those of other model diatoms. Iron-coordinated molecular responses demonstrated some agreement between gene expression and protein abundance, including iron-starvation-induced-proteins, a putative iron transport system and components of photosynthesis and the Calvin cycle. Pseudo-nitzschia granii distinctly differentially expresses genes encoding proteins involved in iron-independent photosynthetic electron transport, urea acquisition and vitamin synthesis. We show that P. granii is unique among studied diatoms in its physiology stemming from distinct cellular responses, which may underlie its ability to subsist in low iron regions and rapidly bloom to outcompete other diatom taxa following iron enrichment.}, } @article {pmid30116836, year = {2018}, author = {Tsuji, A and Kozawa, M and Tokuda, K and Enomoto, T and Koyanagi, T}, title = {Robust Domination of Lactobacillus sakei in Microbiota During Traditional Japanese Sake Starter Yamahai-Moto Fermentation and the Accompanying Changes in Metabolites.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1498-1505}, pmid = {30116836}, issn = {1432-0991}, mesh = {Bacteria/classification/genetics/*isolation & purification/metabolism ; Fermentation ; Fungi/classification/genetics/*isolation & purification/metabolism ; High-Throughput Nucleotide Sequencing ; Lactobacillus sakei/genetics/isolation & purification/*metabolism ; *Microbiota ; Oryza/*chemistry/metabolism/microbiology ; Wine/*analysis/*microbiology ; }, abstract = {The successful production of sake (Japanese rice wine) is brought about by drastic changes in microbial flora and chemical components during fermentation. In the traditional manufacturing process of sake starter (yamahai-moto), spontaneous growth of lactic acid bacteria suppresses inappropriate microorganisms and prepares the optimum environment for the alcohol fermentative yeast. In this study, we analyzed the changes in bacterial flora and chemical components of yamahai-moto. High-throughput next-generation sequencing (NGS) of the 16S ribosomal RNA gene V4 region revealed that various kinds of bacteria, including nitrate-reducing bacteria, existed in the early fermentation stage; however, Lactobacillus sakei then increased drastically to become dominant in the middle stage. Interestingly, this result was different from that obtained in the previous year at the same manufacturer; the early-stage major bacterium was Lactobacillus acidipiscis. Lactic acid, glucose, isomaltose, and total free amino acids increased throughout the fermentation process, which was attributable to the metabolism of L. sakei and the koji mold. It is noteworthy that significant ornithine accumulation and arginine consumption were observed from the middle to late stages. Thirty-eight percent of the L. sakei isolates from yamahai-moto exhibited significant ornithine production, indicating that the arginine deiminase pathway of L. sakei was working to survive the extremely low pH environment of the moto after the middle stage. This is the first report that includes concurrent analyses of the NGS-based bacterial flora and chemical components of yamahai-moto, providing further knowledge to help understand and improve the process of sake brewing.}, } @article {pmid30116102, year = {2018}, author = {Tabl, AA and Alkhateeb, A and Pham, HQ and Rueda, L and ElMaraghy, W and Ngom, A}, title = {A Novel Approach for Identifying Relevant Genes for Breast Cancer Survivability on Specific Therapies.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318790266}, pmid = {30116102}, issn = {1176-9343}, abstract = {Analyzing the genetic activity of breast cancer survival for a specific type of therapy provides a better understanding of the body response to the treatment and helps select the best course of action and while leading to the design of drugs based on gene activity. In this work, we use supervised and nonsupervised machine learning methods to deal with a multiclass classification problem in which we label the samples based on the combination of the 5-year survivability and treatment; we focus on hormone therapy, radiotherapy, and surgery. The proposed nonsupervised hierarchical models are created to find the highest separability between combinations of the classes. The supervised model consists of a combination of feature selection techniques and efficient classifiers used to find a potential set of biomarker genes specific to response to therapy. The results show that different models achieve different performance scores with accuracies ranging from 80.9% to 100%. We have investigated the roles of many biomarkers through the literature and found that some of the discriminative genes in the computational model such as ZC3H11A, VAX2, MAF1, and ZFP91 are related to breast cancer and other types of cancer.}, } @article {pmid30116036, year = {2018}, author = {Waage, J and Standl, M and Curtin, JA and Jessen, LE and Thorsen, J and Tian, C and Schoettler, N and , and , and Flores, C and Abdellaoui, A and Ahluwalia, TS and Alves, AC and Amaral, AFS and Antó, JM and Arnold, A and Barreto-Luis, A and Baurecht, H and van Beijsterveldt, CEM and Bleecker, ER and Bonàs-Guarch, S and Boomsma, DI and Brix, S and Bunyavanich, S and Burchard, EG and Chen, Z and Curjuric, I and Custovic, A and den Dekker, HT and Dharmage, SC and Dmitrieva, J and Duijts, L and Ege, MJ and Gauderman, WJ and Georges, M and Gieger, C and Gilliland, F and Granell, R and Gui, H and Hansen, T and Heinrich, J and Henderson, J and Hernandez-Pacheco, N and Holt, P and Imboden, M and Jaddoe, VWV and Jarvelin, MR and Jarvis, DL and Jensen, KK and Jónsdóttir, I and Kabesch, M and Kaprio, J and Kumar, A and Lee, YA and Levin, AM and Li, X and Lorenzo-Diaz, F and Melén, E and Mercader, JM and Meyers, DA and Myers, R and Nicolae, DL and Nohr, EA and Palviainen, T and Paternoster, L and Pennell, CE and Pershagen, G and Pino-Yanes, M and Probst-Hensch, NM and Rüschendorf, F and Simpson, A and Stefansson, K and Sunyer, J and Sveinbjornsson, G and Thiering, E and Thompson, PJ and Torrent, M and Torrents, D and Tung, JY and Wang, CA and Weidinger, S and Weiss, S and Willemsen, G and Williams, LK and Ober, C and Hinds, DA and Ferreira, MA and Bisgaard, H and Strachan, DP and Bønnelykke, K}, title = {Author Correction: Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1343}, doi = {10.1038/s41588-018-0197-6}, pmid = {30116036}, issn = {1546-1718}, abstract = {In the version of this article initially published, in Fig. 3, the y-axis numbering did not match the log scale indicated in the axis label. The error has been corrected in the HTML and PDF version of the article.}, } @article {pmid30115963, year = {2018}, author = {}, title = {Rising to the Ebola challenge, again.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {965}, doi = {10.1038/s41564-018-0243-2}, pmid = {30115963}, issn = {2058-5276}, } @article {pmid30115810, year = {2018}, author = {Maloy, J}, title = {The universe in a classroom.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {718}, doi = {10.1126/science.361.6403.718}, pmid = {30115810}, issn = {1095-9203}, } @article {pmid30115809, year = {2018}, author = {Greenblatt, EJ and Spradling, AC}, title = {Fragile X mental retardation 1 gene enhances the translation of large autism-related proteins.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {709-712}, doi = {10.1126/science.aas9963}, pmid = {30115809}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Autistic Disorder/genetics/*metabolism ; Drosophila Proteins/genetics/*physiology ; Drosophila melanogaster ; Embryo, Nonmammalian/abnormalities ; Fragile X Mental Retardation Protein/genetics/*physiology ; Gene Knockdown Techniques ; Humans ; Nervous System Malformations/*genetics ; Oocytes ; *Protein Biosynthesis ; RNA, Messenger/genetics/metabolism ; }, abstract = {Mutations in the fragile X mental retardation 1 gene (FMR1) cause the most common inherited human autism spectrum disorder. FMR1 influences messenger RNA (mRNA) translation, but identifying functional targets has been difficult. We analyzed quiescent Drosophila oocytes, which, like neural synapses, depend heavily on translating stored mRNA. Ribosome profiling revealed that FMR1 enhances rather than represses the translation of mRNAs that overlap previously identified FMR1 targets, and acts preferentially on large proteins. Human homologs of at least 20 targets are associated with dominant intellectual disability, and 30 others with recessive neurodevelopmental dysfunction. Stored oocytes lacking FMR1 usually generate embryos with severe neural defects, unlike stored wild-type oocytes, which suggests that translation of multiple large proteins by stored mRNAs is defective in fragile X syndrome and possibly other autism spectrum disorders.}, } @article {pmid30115808, year = {2018}, author = {Hu, L and Mateo, P and Ye, M and Zhang, X and Berset, JD and Handrick, V and Radisch, D and Grabe, V and Köllner, TG and Gershenzon, J and Robert, CAM and Erb, M}, title = {Plant iron acquisition strategy exploited by an insect herbivore.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {694-697}, doi = {10.1126/science.aat4082}, pmid = {30115808}, issn = {1095-9203}, mesh = {Animals ; Benzoxazines/*metabolism ; Coleoptera ; *Herbivory ; Host-Parasite Interactions ; Iron/*metabolism ; Larva/metabolism/physiology ; Plant Roots/*metabolism/*parasitology ; *Secondary Metabolism ; Zea mays/*metabolism/*parasitology ; }, abstract = {Insect herbivores depend on their host plants to acquire macro- and micronutrients. Here we asked how a specialist herbivore and damaging maize pest, the western corn rootworm, finds and accesses plant-derived micronutrients. We show that the root-feeding larvae use complexes between iron and benzoxazinoid secondary metabolites to identify maize as a host, to forage within the maize root system, and to increase their growth. Maize plants use these same benzoxazinoids for protection against generalist herbivores and, as shown here, for iron uptake. We identify an iron transporter that allows the corn rootworm to benefit from complexes between iron and benzoxazinoids. Thus, foraging for an essential plant-derived complex between a micronutrient and a secondary metabolite shapes the interaction between maize and a specialist herbivore.}, } @article {pmid30115807, year = {2018}, author = {Grandjean, D and Coutiño-Gonzalez, E and Cuong, NT and Fron, E and Baekelant, W and Aghakhani, S and Schlexer, P and D'Acapito, F and Banerjee, D and Roeffaers, MBJ and Nguyen, MT and Hofkens, J and Lievens, P}, title = {Origin of the bright photoluminescence of few-atom silver clusters confined in LTA zeolites.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {686-690}, doi = {10.1126/science.aaq1308}, pmid = {30115807}, issn = {1095-9203}, abstract = {Silver (Ag) clusters confined in matrices possess remarkable luminescence properties, but little is known about their structural and electronic properties. We characterized the bright green luminescence of Ag clusters confined in partially exchanged Ag-Linde Type A (LTA) zeolites by means of a combination of x-ray excited optical luminescence-extended x-ray absorption fine structure, time-dependent-density functional theory calculations, and time-resolved spectroscopy. A mixture of tetrahedral Ag4(H2O) x 2+ (x = 2 and x = 4) clusters occupies the center of a fraction of the sodalite cages. Their optical properties originate from a confined two-electron superatom quantum system with hybridized Ag and water O orbitals delocalized over the cluster. Upon excitation, one electron of the s-type highest occupied molecular orbital is promoted to the p-type lowest unoccupied molecular orbitals and relaxes through enhanced intersystem crossing into long-lived triplet states.}, } @article {pmid30115806, year = {2018}, author = {Chowdhury, MR and Steffes, J and Huey, BD and McCutcheon, JR}, title = {3D printed polyamide membranes for desalination.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {682-686}, doi = {10.1126/science.aar2122}, pmid = {30115806}, issn = {1095-9203}, abstract = {Polyamide thickness and roughness have been identified as critical properties that affect thin-film composite membrane performance for reverse osmosis. Conventional formation methodologies lack the ability to control these properties independently with high resolution or precision. An additive approach is presented that uses electrospraying to deposit monomers directly onto a substrate, where they react to form polyamide. The small droplet size coupled with low monomer concentrations result in polyamide films that are smoother and thinner than conventional polyamides, while the additive nature of the approach allows for control of thickness and roughness. Polyamide films are formed with a thickness that is controllable down to 4-nanometer increments and a roughness as low as 2 nanometers while still exhibiting good permselectivity relative to a commercial benchmarking membrane.}, } @article {pmid30115805, year = {2018}, author = {Celliers, PM and Millot, M and Brygoo, S and McWilliams, RS and Fratanduono, DE and Rygg, JR and Goncharov, AF and Loubeyre, P and Eggert, JH and Peterson, JL and Meezan, NB and Le Pape, S and Collins, GW and Jeanloz, R and Hemley, RJ}, title = {Insulator-metal transition in dense fluid deuterium.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {677-682}, doi = {10.1126/science.aat0970}, pmid = {30115805}, issn = {1095-9203}, abstract = {Dense fluid metallic hydrogen occupies the interiors of Jupiter, Saturn, and many extrasolar planets, where pressures reach millions of atmospheres. Planetary structure models must describe accurately the transition from the outer molecular envelopes to the interior metallic regions. We report optical measurements of dynamically compressed fluid deuterium to 600 gigapascals (GPa) that reveal an increasing refractive index, the onset of absorption of visible light near 150 GPa, and a transition to metal-like reflectivity (exceeding 30%) near 200 GPa, all at temperatures below 2000 kelvin. Our measurements and analysis address existing discrepancies between static and dynamic experiments for the insulator-metal transition in dense fluid hydrogen isotopes. They also provide new benchmarks for the theoretical calculations used to construct planetary models.}, } @article {pmid30115804, year = {2018}, author = {Aguilar, J and Monaenkova, D and Linevich, V and Savoie, W and Dutta, B and Kuan, HS and Betterton, MD and Goodisman, MAD and Goldman, DI}, title = {Collective clog control: Optimizing traffic flow in confined biological and robophysical excavation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {672-677}, doi = {10.1126/science.aan3891}, pmid = {30115804}, issn = {1095-9203}, abstract = {Groups of interacting active particles, insects, or humans can form clusters that hinder the goals of the collective; therefore, development of robust strategies for control of such clogs is essential, particularly in confined environments. Our biological and robophysical excavation experiments, supported by computational and theoretical models, reveal that digging performance can be robustly optimized within the constraints of narrow tunnels by individual idleness and retreating. Tools from the study of dense particulate ensembles elucidate how idleness reduces the frequency of flow-stopping clogs and how selective retreating reduces cluster dissolution time for the rare clusters that still occur. Our results point to strategies by which dense active matter and swarms can become task capable without sophisticated sensing, planning, and global control of the collective.}, } @article {pmid30115803, year = {2018}, author = {Kaldre, D and Klose, I and Maulide, N}, title = {Stereodivergent synthesis of 1,4-dicarbonyls by traceless charge-accelerated sulfonium rearrangement.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {664-667}, doi = {10.1126/science.aat5883}, pmid = {30115803}, issn = {1095-9203}, abstract = {The chemistry of the carbonyl group is essential to modern organic synthesis. The preparation of substituted, enantioenriched 1,3- or 1,5-dicarbonyls is well developed, as their disconnection naturally follows from the intrinsic polarity of the carbonyl group. By contrast, a general enantioselective access to quaternary stereocenters in acyclic 1,4-dicarbonyl systems remains an unresolved problem, despite the tremendous importance of 2,3-substituted 1,4-dicarbonyl motifs in natural products and drug scaffolds. Here we present a broad enantioselective and stereodivergent strategy to access acyclic, polysubstituted 1,4-dicarbonyls via acid-catalyzed [3,3]-sulfonium rearrangement starting from vinyl sulfoxides and ynamides. The stereochemistry at sulfur governs the absolute sense of chiral induction, whereas the double bond geometry dictates the relative configuration of the final products.}, } @article {pmid30115802, year = {2018}, author = {Monroe, KR}, title = {Harassment charges: Metoo but due process.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {656}, doi = {10.1126/science.aau7986}, pmid = {30115802}, issn = {1095-9203}, mesh = {Female ; Humans ; Male ; Retirement ; Sexual Harassment/*ethics ; United States ; }, } @article {pmid30115801, year = {2018}, author = {Moya, A and , }, title = {Harassment charges: Injustice done?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {655-656}, doi = {10.1126/science.aau7088}, pmid = {30115801}, issn = {1095-9203}, mesh = {Humans ; Sexual Harassment/*legislation & jurisprudence ; United States ; }, } @article {pmid30115800, year = {2018}, author = {Duffy, J}, title = {Harassment charges: Journalists' role.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {655}, doi = {10.1126/science.aau7641}, pmid = {30115800}, issn = {1095-9203}, mesh = {Female ; Humans ; Science ; Sexual Harassment/*prevention & control/*psychology ; Whistleblowing ; Women/*psychology ; }, } @article {pmid30115799, year = {2018}, author = {Zelikova, J and Ramirez, K and Lipps, J and , }, title = {Harassment charges: Enough himpathy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {655}, doi = {10.1126/science.aau6858}, pmid = {30115799}, issn = {1095-9203}, mesh = {Empathy/*ethics ; Humans ; Male ; Science ; Sexual Harassment/*prevention & control/*psychology ; United States ; }, } @article {pmid30115798, year = {2018}, author = {Bongaarts, J and O'Neill, BC}, title = {Global warming policy: Is population left out in the cold?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {650-652}, doi = {10.1126/science.aat8680}, pmid = {30115798}, issn = {1095-9203}, mesh = {*Family Planning Policy ; Global Warming/*prevention & control ; Humans ; *Population Control ; *Population Growth ; }, } @article {pmid30115797, year = {2018}, author = {Aryal, S and Klann, E}, title = {Turning up translation in fragile X syndrome.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {648-649}, doi = {10.1126/science.aau6450}, pmid = {30115797}, issn = {1095-9203}, mesh = {Fragile X Mental Retardation Protein/*genetics ; *Fragile X Syndrome ; Humans ; Protein Biosynthesis ; }, } @article {pmid30115796, year = {2018}, author = {Kanai, M}, title = {Photocatalytic upgrading of natural gas.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {647-648}, doi = {10.1126/science.aau5379}, pmid = {30115796}, issn = {1095-9203}, mesh = {*Biofuels ; Methane ; *Natural Gas ; }, } @article {pmid30115795, year = {2018}, author = {Ablasser, A}, title = {Phase separation focuses DNA sensing.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {646-647}, doi = {10.1126/science.aau6019}, pmid = {30115795}, issn = {1095-9203}, mesh = {*DNA ; }, } @article {pmid30115794, year = {2018}, author = {Quintanilla, M and Liz-Marzán, LM}, title = {Caged clusters shine brighter.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {645}, doi = {10.1126/science.aau5256}, pmid = {30115794}, issn = {1095-9203}, } @article {pmid30115793, year = {2018}, author = {Kim, K and Goentoro, L}, title = {Choosing the right input in cell signaling.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {643-644}, doi = {10.1126/science.aau6457}, pmid = {30115793}, issn = {1095-9203}, mesh = {*Signal Transduction ; }, } @article {pmid30115792, year = {2018}, author = {Kliebenstein, DJ}, title = {Plant nutrient acquisition entices herbivore.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {642-643}, doi = {10.1126/science.aau6017}, pmid = {30115792}, issn = {1095-9203}, mesh = {Food ; *Herbivory ; *Plants ; }, } @article {pmid30115791, year = {2018}, author = {Kupferschmidt, K}, title = {Tide of lies.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {636-641}, doi = {10.1126/science.361.6403.636}, pmid = {30115791}, issn = {1095-9203}, mesh = {Clinical Trials as Topic ; Fractures, Bone/*prevention & control ; Humans ; *Scientific Misconduct ; Universities ; }, } @article {pmid30115790, year = {2018}, author = {Pennisi, E}, title = {Detailed genome maps paths to better wheat.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {635}, doi = {10.1126/science.361.6403.635}, pmid = {30115790}, issn = {1095-9203}, mesh = {Breeding ; *Chromosome Mapping ; Chromosomes, Plant/*genetics ; Edible Grain/*genetics ; Genome, Plant ; Triticum/*genetics ; }, } @article {pmid30115789, year = {2018}, author = {Wade, L}, title = {Study reignites debate about when Thera blew its top.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {634}, doi = {10.1126/science.361.6403.634}, pmid = {30115789}, issn = {1095-9203}, } @article {pmid30115788, year = {2018}, author = {Hutson, M}, title = {AI takes on video games in quest for common sense.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {632-633}, doi = {10.1126/science.361.6403.632}, pmid = {30115788}, issn = {1095-9203}, mesh = {*Artificial Intelligence ; Humans ; *Video Games ; }, } @article {pmid30115787, year = {2018}, author = {Zainzinger, V}, title = {Critics pan EPA plan for weighing toxic chemical risks.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {631-632}, doi = {10.1126/science.361.6403.631}, pmid = {30115787}, issn = {1095-9203}, mesh = {Guidelines as Topic/*standards ; Hazardous Substances/*standards/toxicity ; Humans ; Peer Review/*standards ; Risk ; Safety ; United States ; *United States Environmental Protection Agency ; }, } @article {pmid30115786, year = {2018}, author = {Kupferschmidt, K}, title = {New case of alleged bullying rocks the Max Planck Society.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {630-631}, doi = {10.1126/science.361.6403.630}, pmid = {30115786}, issn = {1095-9203}, mesh = {*Academies and Institutes ; *Bullying ; Empathy ; Fear ; Germany ; Humans ; Laboratories ; Meditation ; *Societies, Scientific ; }, } @article {pmid30115785, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {628-629}, doi = {10.1126/science.361.6403.628}, pmid = {30115785}, issn = {1095-9203}, } @article {pmid30115784, year = {2018}, author = {Garces, LM}, title = {Don't lose race-conscious policies.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {627}, doi = {10.1126/science.aau9807}, pmid = {30115784}, issn = {1095-9203}, mesh = {Humans ; Public Policy ; *Racism ; *School Admission Criteria ; Universities ; }, } @article {pmid30115783, year = {2018}, author = {, and , and Appels, R and Eversole, K and Feuillet, C and Keller, B and Rogers, J and Stein, N and , and Pozniak, CJ and Stein, N and Choulet, F and Distelfeld, A and Eversole, K and Poland, J and Rogers, J and Ronen, G and Sharpe, AG and , and Pozniak, C and Ronen, G and Stein, N and Barad, O and Baruch, K and Choulet, F and Keeble-Gagnère, G and Mascher, M and Sharpe, AG and Ben-Zvi, G and Josselin, AA and , and Stein, N and Mascher, M and Himmelbach, A and , and Choulet, F and Keeble-Gagnère, G and Mascher, M and Rogers, J and Balfourier, F and Gutierrez-Gonzalez, J and Hayden, M and Josselin, AA and Koh, C and Muehlbauer, G and Pasam, RK and Paux, E and Pozniak, CJ and Rigault, P and Sharpe, AG and Tibbits, J and Tiwari, V and , and Choulet, F and Keeble-Gagnère, G and Mascher, M and Josselin, AA and Rogers, J and , and Spannagl, M and Choulet, F and Lang, D and Gundlach, H and Haberer, G and Keeble-Gagnère, G and Mayer, KFX and Ormanbekova, D and Paux, E and Prade, V and Šimková, H and Wicker, T and , and Choulet, F and Spannagl, M and Swarbreck, D and Rimbert, H and Felder, M and Guilhot, N and Gundlach, H and Haberer, G and Kaithakottil, G and Keilwagen, J and Lang, D and Leroy, P and Lux, T and Mayer, KFX and Twardziok, S and Venturini, L and , and Appels, R and Rimbert, H and Choulet, F and Juhász, A and Keeble-Gagnère, G and , and Choulet, F and Spannagl, M and Lang, D and Abrouk, M and Haberer, G and Keeble-Gagnère, G and Mayer, KFX and Wicker, T and , and Choulet, F and Wicker, T and Gundlach, H and Lang, D and Spannagl, M and , and Lang, D and Spannagl, M and Appels, R and Fischer, I and , and Uauy, C and Borrill, P and Ramirez-Gonzalez, RH and Appels, R and Arnaud, D and Chalabi, S and Chalhoub, B and Choulet, F and Cory, A and Datla, R and Davey, MW and Hayden, M and Jacobs, J and Lang, D and Robinson, SJ and Spannagl, M and Steuernagel, B and Tibbits, J and Tiwari, V and van Ex, F and Wulff, BBH and , and Pozniak, CJ and Robinson, SJ and Sharpe, AG and Cory, A and , and Benhamed, M and Paux, E and Bendahmane, A and Concia, L and Latrasse, D and , and Rogers, J and Jacobs, J and Alaux, M and Appels, R and Bartoš, J and Bellec, A and Berges, H and Doležel, J and Feuillet, C and Frenkel, Z and Gill, B and Korol, A and Letellier, T and Olsen, OA and Šimková, H and Singh, K and Valárik, M and van der Vossen, E and Vautrin, S and Weining, S and , and Korol, A and Frenkel, Z and Fahima, T and Glikson, V and Raats, D and Rogers, J and , and Tiwari, V and Gill, B and Paux, E and Poland, J and , and Doležel, J and Číhalíková, J and Šimková, H and Toegelová, H and Vrána, J and , and Sourdille, P and Darrier, B and , and Appels, R and Spannagl, M and Lang, D and Fischer, I and Ormanbekova, D and Prade, V and , and Barabaschi, D and Cattivelli, L and , and Hernandez, P and Galvez, S and Budak, H and , and Steuernagel, B and Jones, JDG and Witek, K and Wulff, BBH and Yu, G and , and Small, I and Melonek, J and Zhou, R and , and Juhász, A and Belova, T and Appels, R and Olsen, OA and , and Kanyuka, K and King, R and , and Nilsen, K and Walkowiak, S and Pozniak, CJ and Cuthbert, R and Datla, R and Knox, R and Wiebe, K and Xiang, D and , and Rohde, A and Golds, T and , and Doležel, J and Čížková, J and Tibbits, J and , and Budak, H and Akpinar, BA and Biyiklioglu, S and , and Muehlbauer, G and Poland, J and Gao, L and Gutierrez-Gonzalez, J and N'Daiye, A and , and Doležel, J and Šimková, H and Číhalíková, J and Kubaláková, M and Šafář, J and Vrána, J and , and Berges, H and Bellec, A and Vautrin, S and , and Alaux, M and Alfama, F and Adam-Blondon, AF and Flores, R and Guerche, C and Letellier, T and Loaec, M and Quesneville, H and , and , and Pozniak, CJ and Sharpe, AG and Walkowiak, S and Budak, H and Condie, J and Ens, J and Koh, C and Maclachlan, R and Tan, Y and Wicker, T and , and Choulet, F and Paux, E and Alberti, A and Aury, JM and Balfourier, F and Barbe, V and Couloux, A and Cruaud, C and Labadie, K and Mangenot, S and Wincker, P and , and Gill, B and Kaur, G and Luo, M and Sehgal, S and , and Singh, K and Chhuneja, P and Gupta, OP and Jindal, S and Kaur, P and Malik, P and Sharma, P and Yadav, B and , and Singh, NK and Khurana, J and Chaudhary, C and Khurana, P and Kumar, V and Mahato, A and Mathur, S and Sevanthi, A and Sharma, N and Tomar, RS and , and Rogers, J and Jacobs, J and Alaux, M and Bellec, A and Berges, H and Doležel, J and Feuillet, C and Frenkel, Z and Gill, B and Korol, A and van der Vossen, E and Vautrin, S and , and Gill, B and Kaur, G and Luo, M and Sehgal, S and , and Bartoš, J and Holušová, K and Plíhal, O and , and Clark, MD and Heavens, D and Kettleborough, G and Wright, J and , and Valárik, M and Abrouk, M and Balcárková, B and Holušová, K and Hu, Y and Luo, M and , and Salina, E and Ravin, N and Skryabin, K and Beletsky, A and Kadnikov, V and Mardanov, A and Nesterov, M and Rakitin, A and Sergeeva, E and , and Handa, H and Kanamori, H and Katagiri, S and Kobayashi, F and Nasuda, S and Tanaka, T and Wu, J and , and Appels, R and Hayden, M and Keeble-Gagnère, G and Rigault, P and Tibbits, J and , and Olsen, OA and Belova, T and Cattonaro, F and Jiumeng, M and Kugler, K and Mayer, KFX and Pfeifer, M and Sandve, S and Xun, X and Zhan, B and , and Šimková, H and Abrouk, M and Batley, J and Bayer, PE and Edwards, D and Hayashi, S and Toegelová, H and Tulpová, Z and Visendi, P and , and Weining, S and Cui, L and Du, X and Feng, K and Nie, X and Tong, W and Wang, L and , and Borrill, P and Gundlach, H and Galvez, S and Kaithakottil, G and Lang, D and Lux, T and Mascher, M and Ormanbekova, D and Prade, V and Ramirez-Gonzalez, RH and Spannagl, M and Stein, N and Uauy, C and Venturini, L and , and Stein, N and Appels, R and Eversole, K and Rogers, J and Borrill, P and Cattivelli, L and Choulet, F and Hernandez, P and Kanyuka, K and Lang, D and Mascher, M and Nilsen, K and Paux, E and Pozniak, CJ and Ramirez-Gonzalez, RH and Šimková, H and Small, I and Spannagl, M and Swarbreck, D and Uauy, C}, title = {Shifting the limits in wheat research and breeding using a fully annotated reference genome.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {}, doi = {10.1126/science.aar7191}, pmid = {30115783}, issn = {1095-9203}, mesh = {Atlases as Topic ; Bread ; *Breeding ; *Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; *Genome, Plant ; Molecular Sequence Annotation ; Multigene Family ; Phylogeny ; Quantitative Trait Loci ; Reference Standards ; Transcriptome ; Triticum/anatomy & histology/classification/*genetics/*growth & development ; }, abstract = {An annotated reference sequence representing the hexaploid bread wheat genome in 21 pseudomolecules has been analyzed to identify the distribution and genomic context of coding and noncoding elements across the A, B, and D subgenomes. With an estimated coverage of 94% of the genome and containing 107,891 high-confidence gene models, this assembly enabled the discovery of tissue- and developmental stage-related coexpression networks by providing a transcriptome atlas representing major stages of wheat development. Dynamics of complex gene families involved in environmental adaptation and end-use quality were revealed at subgenome resolution and contextualized to known agronomic single-gene or quantitative trait loci. This community resource establishes the foundation for accelerating wheat research and application through improved understanding of wheat biology and genomics-assisted breeding.}, } @article {pmid30115782, year = {2018}, author = {Ramírez-González, RH and Borrill, P and Lang, D and Harrington, SA and Brinton, J and Venturini, L and Davey, M and Jacobs, J and van Ex, F and Pasha, A and Khedikar, Y and Robinson, SJ and Cory, AT and Florio, T and Concia, L and Juery, C and Schoonbeek, H and Steuernagel, B and Xiang, D and Ridout, CJ and Chalhoub, B and Mayer, KFX and Benhamed, M and Latrasse, D and Bendahmane, A and , and Wulff, BBH and Appels, R and Tiwari, V and Datla, R and Choulet, F and Pozniak, CJ and Provart, NJ and Sharpe, AG and Paux, E and Spannagl, M and Bräutigam, A and Uauy, C}, title = {The transcriptional landscape of polyploid wheat.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {}, doi = {10.1126/science.aar6089}, pmid = {30115782}, issn = {1095-9203}, mesh = {Bread ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; Genome, Plant ; *Polyploidy ; RNA, Plant/genetics ; Sequence Analysis, RNA ; *Transcription, Genetic ; Triticum/*genetics/growth & development ; }, abstract = {The coordinated expression of highly related homoeologous genes in polyploid species underlies the phenotypes of many of the world's major crops. Here we combine extensive gene expression datasets to produce a comprehensive, genome-wide analysis of homoeolog expression patterns in hexaploid bread wheat. Bias in homoeolog expression varies between tissues, with ~30% of wheat homoeologs showing nonbalanced expression. We found expression asymmetries along wheat chromosomes, with homoeologs showing the largest inter-tissue, inter-cultivar, and coding sequence variation, most often located in high-recombination distal ends of chromosomes. These transcriptionally dynamic genes potentially represent the first steps toward neo- or subfunctionalization of wheat homoeologs. Coexpression networks reveal extensive coordination of homoeologs throughout development and, alongside a detailed expression atlas, provide a framework to target candidate genes underpinning agronomic traits in wheat.}, } @article {pmid30115781, year = {2018}, author = {Altmann, Y and McLaughlin, S and Padgett, MJ and Goyal, VK and Hero, AO and Faccio, D}, title = {Quantum-inspired computational imaging.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {}, doi = {10.1126/science.aat2298}, pmid = {30115781}, issn = {1095-9203}, abstract = {Computational imaging combines measurement and computational methods with the aim of forming images even when the measurement conditions are weak, few in number, or highly indirect. The recent surge in quantum-inspired imaging sensors, together with a new wave of algorithms allowing on-chip, scalable and robust data processing, has induced an increase of activity with notable results in the domain of low-light flux imaging and sensing. We provide an overview of the major challenges encountered in low-illumination (e.g., ultrafast) imaging and how these problems have recently been addressed for imaging applications in extreme conditions. These methods provide examples of the future imaging solutions to be developed, for which the best results are expected to arise from an efficient codesign of the sensors and data analysis tools.}, } @article {pmid30115746, year = {2018}, author = {Petryk, N and Dalby, M and Wenger, A and Stromme, CB and Strandsby, A and Andersson, R and Groth, A}, title = {MCM2 promotes symmetric inheritance of modified histones during DNA replication.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1389-1392}, doi = {10.1126/science.aau0294}, pmid = {30115746}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Animals ; Cell Division ; Cell Line ; Chromatids/metabolism ; *DNA Replication ; Embryonic Stem Cells ; *Histone Code ; Histones/*metabolism ; Mice ; Minichromosome Maintenance Complex Component 2/genetics/*metabolism ; Protein Processing, Post-Translational ; }, abstract = {During genome replication, parental histones are recycled to newly replicated DNA with their posttranslational modifications (PTMs). Whether sister chromatids inherit modified histones evenly remains unknown. We measured histone PTM partition to sister chromatids in embryonic stem cells. We found that parental histones H3-H4 segregate to both daughter DNA strands with a weak leading-strand bias, skewing partition at topologically associating domain (TAD) borders and enhancers proximal to replication initiation zones. Segregation of parental histones to the leading strand increased markedly in cells with histone-binding mutations in MCM2, part of the replicative helicase, exacerbating histone PTM sister chromatid asymmetry. This work reveals how histones are inherited to sister chromatids and identifies a mechanism by which the replication machinery ensures symmetric cell division.}, } @article {pmid30115745, year = {2018}, author = {Yu, C and Gan, H and Serra-Cardona, A and Zhang, L and Gan, S and Sharma, S and Johansson, E and Chabes, A and Xu, RM and Zhang, Z}, title = {A mechanism for preventing asymmetric histone segregation onto replicating DNA strands.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6409}, pages = {1386-1389}, doi = {10.1126/science.aat8849}, pmid = {30115745}, issn = {1095-9203}, support = {R35 GM118015/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA/genetics/metabolism ; DNA Polymerase II/genetics ; *DNA Replication ; *Epigenesis, Genetic ; Gene Deletion ; Heterochromatin/chemistry/metabolism ; Histones/*metabolism ; Nucleosomes/metabolism ; Protein Multimerization ; Saccharomycetales/genetics/*metabolism ; }, abstract = {How parental histone (H3-H4)2 tetramers, the primary carriers of epigenetic modifications, are transferred onto leading and lagging strands of DNA replication forks for epigenetic inheritance remains elusive. Here we show that parental (H3-H4)2 tetramers are assembled into nucleosomes onto both leading and lagging strands, with a slight preference for lagging strands. The lagging-strand preference increases markedly in budding yeast cells lacking Dpb3 and Dpb4, two subunits of the leading strand DNA polymerase, Pol ε, owing to the impairment of parental (H3-H4)2 transfer to leading strands. Dpb3-Dpb4 binds H3-H4 in vitro and participates in the inheritance of heterochromatin. These results indicate that different proteins facilitate the transfer of parental (H3-H4)2 onto leading versus lagging strands and that Dbp3-Dpb4 plays an important role in this poorly understood process.}, } @article {pmid30115744, year = {2018}, author = {Bittner, S and Guazzotti, S and Zeng, Y and Hu, X and Yılmaz, H and Kim, K and Oh, SS and Wang, QJ and Hess, O and Cao, H}, title = {Suppressing spatiotemporal lasing instabilities with wave-chaotic microcavities.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1225-1231}, doi = {10.1126/science.aas9437}, pmid = {30115744}, issn = {1095-9203}, abstract = {Spatiotemporal instabilities are widespread phenomena resulting from complexity and nonlinearity. In broad-area edge-emitting semiconductor lasers, the nonlinear interactions of multiple spatial modes with the active medium can result in filamentation and spatiotemporal chaos. These instabilities degrade the laser performance and are extremely challenging to control. We demonstrate a powerful approach to suppress spatiotemporal instabilities using wave-chaotic or disordered cavities. The interference of many propagating waves with random phases in such cavities disrupts the formation of self-organized structures such as filaments, resulting in stable lasing dynamics. Our method provides a general and robust scheme to prevent the formation and growth of nonlinear instabilities for a large variety of high-power lasers.}, } @article {pmid30115743, year = {2018}, author = {Wang, D and Kong, L and Fan, P and Chen, H and Zhu, S and Liu, W and Cao, L and Sun, Y and Du, S and Schneeloch, J and Zhong, R and Gu, G and Fu, L and Ding, H and Gao, HJ}, title = {Evidence for Majorana bound states in an iron-based superconductor.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {333-335}, doi = {10.1126/science.aao1797}, pmid = {30115743}, issn = {1095-9203}, abstract = {The search for Majorana bound states (MBSs) has been fueled by the prospect of using their non-Abelian statistics for robust quantum computation. Two-dimensional superconducting topological materials have been predicted to host MBSs as zero-energy modes in vortex cores. By using scanning tunneling spectroscopy on the superconducting Dirac surface state of the iron-based superconductor FeTe0.55Se0.45, we observed a sharp zero-bias peak inside a vortex core that does not split when moving away from the vortex center. The evolution of the peak under varying magnetic field, temperature, and tunneling barrier is consistent with the tunneling to a nearly pure MBS, separated from nontopological bound states. This observation offers a potential platform for realizing and manipulating MBSs at a relatively high temperature.}, } @article {pmid30115666, year = {2018}, author = {Burén, S and López-Torrejón, G and Rubio, LM}, title = {Extreme bioengineering to meet the nitrogen challenge.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {8849-8851}, pmid = {30115666}, issn = {1091-6490}, mesh = {*Bioengineering ; Biomedical Engineering ; *Nitrogen ; }, } @article {pmid30115665, year = {2018}, author = {Brown, ST and Basu, A and Ding, X and Christensen, JN and DePaolo, DJ}, title = {Uranium isotope fractionation by abiotic reductive precipitation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8688-8693}, pmid = {30115665}, issn = {1091-6490}, abstract = {Significant uranium (U) isotope fractionation has been observed during abiotic reduction of aqueous U, counter to the expectation that uranium isotopes are only fractionated by bioassociated enzymatic reduction. In our experiments, aqueous U is removed from solution by reductive precipitation onto the surfaces of synthetic iron monosulfide. The magnitude of uranium isotopic fractionation increases with decreasing aqueous U removal rate and with increasing amounts of neutrally charged aqueous Ca-U-CO3 species. Our discovery means that abiotic U isotope fractionation likely occurs in any reducing environment with aqueous Ca ≥ 1 mM, and that the magnitude of isotopic fractionation changes in response to changes in aqueous major ion concentrations that affect U speciation. Our results have implications for the study of anoxia in the ancient oceans and other environments.}, } @article {pmid30115561, year = {2018}, author = {Palmer, A and Criss, AK}, title = {Gonococcal Defenses against Antimicrobial Activities of Neutrophils.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {1022-1034}, pmid = {30115561}, issn = {1878-4380}, support = {R01 AI097312/AI/NIAID NIH HHS/United States ; R01 AI127793/AI/NIAID NIH HHS/United States ; T32 AI007046/AI/NIAID NIH HHS/United States ; U19 AI084044/AI/NIAID NIH HHS/United States ; }, abstract = {Neisseria gonorrhoeae initiates a strong local immune response that is characterized by copious recruitment of neutrophils to the site of infection. Neutrophils neutralize microbes by mechanisms that include phagocytosis, extracellular trap formation, production of reactive oxygen species, and the delivery of antimicrobial granular contents. However, neutrophils do not clear infection with N. gonorrhoeae. N. gonorrhoeae not only expresses factors that defend against neutrophil bactericidal components, but it also manipulates neutrophil production and release of these components. In this review, we highlight the numerous approaches used by N. gonorrhoeae to survive exposure to neutrophils both intracellularly and extracellularly. These approaches reflect the exquisite adaptation of N. gonorrhoeae to its obligate human host.}, } @article {pmid30115123, year = {2018}, author = {Asgedom, SW and Atey, TM and Desse, TA}, title = {Correction to: Antihypertensive medication adherence and associated factors among adult hypertensive patients at Jimma University Specialized Hospital, southwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {592}, pmid = {30115123}, issn = {1756-0500}, abstract = {After publication of our article [1] we became aware that we had not obtained permission to reproduce the questions from the eight-item Morisky's Medication Adherence Scale. The table in this Correction replaces Table 2 in our article. In addition, the second number for the MMAS-8 question 2 was incorrect and has been updated to 223(79.6).}, } @article {pmid30115122, year = {2018}, author = {Pérez-Jaramillo, JE and Carrión, VJ and de Hollander, M and Raaijmakers, JM}, title = {The wild side of plant microbiomes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {143}, pmid = {30115122}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Domestication ; Microbiota ; Phylogeny ; Plant Roots/*microbiology ; Plants/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, } @article {pmid30115114, year = {2018}, author = {Biks, GA and Tariku, A and Wassie, MM and Derso, T}, title = {Mother's Infant and Young Child Feeding (IYCF) knowledge improved timely initiation of complementary feeding of children aged 6-24 months in the rural population of northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {593}, pmid = {30115114}, issn = {1756-0500}, mesh = {Cross-Sectional Studies ; Ethiopia ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Infant ; *Infant Nutritional Physiological Phenomena ; Mothers ; *Rural Population ; }, abstract = {OBJECTIVES: Appropriate complementary feeding is vital to reduce young child morbidity and mortality. However, it continues as sub-optimal in Ethiopia, and literatures are also scarce. Therefore, this study aimed to determine timely initiation of complementary feeding and associated factors among mothers with children aged 6-24 months in the rural population of northwest Ethiopia. In the community based cross-sectional study, data on child feeding practices, individual and household characteristics were collected in Dabat Demographic Surveillance System site, Dabat District, northwest Ethiopia from 01 May to 29 June 2015. The bivariate and backward stepwise multivariable statistical methods were carried out to identify factors associated with timely initiation of complementary feeding.

RESULTS: About 53.8% [95% CI 45.9, 61.7] and 4.6% [95% CI 1.3, 7.9] of children were found with timely initiation of complementary feeding and had minimum dietary diversity, respectively. The odds of timely initiation of complementary feeding was higher among mothers with medium [AOR = 2.34, 95% CI 1.54, 3.81] and high [AOR = 2.10, 95% CI 1.41, 3.87] mother's IYCF knowledge. In Dabat district, complementary feeding practice is lower. Thus, efforts should be strengthened to boost mother's IYCF knowledge.}, } @article {pmid30115066, year = {2018}, author = {Santos-Zavaleta, A and Sánchez-Pérez, M and Salgado, H and Velázquez-Ramírez, DA and Gama-Castro, S and Tierrafría, VH and Busby, SJW and Aquino, P and Fang, X and Palsson, BO and Galagan, JE and Collado-Vides, J}, title = {A unified resource for transcriptional regulation in Escherichia coli K-12 incorporating high-throughput-generated binding data into RegulonDB version 10.0.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {91}, pmid = {30115066}, issn = {1741-7007}, support = {R01GM110597-3/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Our understanding of the regulation of gene expression has benefited from the availability of high-throughput technologies that interrogate the whole genome for the binding of specific transcription factors and gene expression profiles. In the case of widely used model organisms, such as Escherichia coli K-12, the new knowledge gained from these approaches needs to be integrated with the legacy of accumulated knowledge from genetic and molecular biology experiments conducted in the pre-genomic era in order to attain the deepest level of understanding possible based on the available data.

RESULTS: In this paper, we describe an expansion of RegulonDB, the database containing the rich legacy of decades of classic molecular biology experiments supporting what we know about gene regulation and operon organization in E. coli K-12, to include the genome-wide dataset collections from 32 ChIP and 19 gSELEX publications, in addition to around 60 genome-wide expression profiles relevant to the functional significance of these datasets and used in their curation. Three essential features for the integration of this information coming from different methodological approaches are: first, a controlled vocabulary within an ontology for precisely defining growth conditions; second, the criteria to separate elements with enough evidence to consider them involved in gene regulation from isolated transcription factor binding sites without such support; and third, an expanded computational model supporting this knowledge. Altogether, this constitutes the basis for adequately gathering and enabling the comparisons and integration needed to manage and access such wealth of knowledge.

CONCLUSIONS: This version 10.0 of RegulonDB is a first step toward what should become the unifying access point for current and future knowledge on gene regulation in E. coli K-12. Furthermore, this model platform and associated methodologies and criteria can be emulated for gathering knowledge on other microbial organisms.}, } @article {pmid30115034, year = {2018}, author = {Iung, LHS and Mulder, HA and Neves, HHR and Carvalheiro, R}, title = {Genomic regions underlying uniformity of yearling weight in Nellore cattle evaluated under different response variables.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {619}, pmid = {30115034}, issn = {1471-2164}, support = {308636/2014-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)/ ; 88881.131673/2016-01//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (BR)/ ; }, mesh = {Animals ; Body Weight/*genetics ; Breeding ; Cattle/*genetics ; Conserved Sequence ; Genome-Wide Association Study/veterinary ; Genotype ; Models, Genetic ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; }, abstract = {BACKGROUND: In livestock, residual variance has been studied because of the interest to improve uniformity of production. Several studies have provided evidence that residual variance is partially under genetic control; however, few investigations have elucidated genes that control it. The aim of this study was to identify genomic regions associated with within-family residual variance of yearling weight (YW; N = 423) in Nellore bulls with high density SNP data, using different response variables. For this, solutions from double hierarchical generalized linear models (DHGLM) were used to provide the response variables, as follows: a DGHLM assuming non-null genetic correlation between mean and residual variance (rmv ≠ 0) to obtain deregressed EBV for mean (dEBVm) and residual variance (dEBVv); and a DHGLM assuming rmv = 0 to obtain two alternative response variables for residual variance, dEBVv_r0 and log-transformed variance of estimated residuals (ln_[Formula: see text]).

RESULTS: The dEBVm and dEBVv were highly correlated, resulting in common regions associated with mean and residual variance of YW. However, higher effects on variance than the mean showed that these regions had effects on the variance beyond scale effects. More independent association results between mean and residual variance were obtained when null rmv was assumed. While 13 and 4 single nucleotide polymorphisms (SNPs) showed a strong association (Bayes Factor > 20) with dEBVv and ln_[Formula: see text], respectively, only suggestive signals were found for dEBVv_r0. All overlapping 1-Mb windows among top 20 between dEBVm and dEBVv were previously associated with growth traits. The potential candidate genes for uniformity are involved in metabolism, stress, inflammatory and immune responses, mineralization, neuronal activity and bone formation.

CONCLUSIONS: It is necessary to use a strategy like assuming null rmv to obtain genomic regions associated with uniformity that are not associated with the mean. Genes involved not only in metabolism, but also stress, inflammatory and immune responses, mineralization, neuronal activity and bone formation were the most promising biological candidates for uniformity of YW. Although no clear evidence of using a specific response variable was found, we recommend consider different response variables to study uniformity to increase evidence on candidate regions and biological mechanisms behind it.}, } @article {pmid30115030, year = {2018}, author = {Gali, KK and Liu, Y and Sindhu, A and Diapari, M and Shunmugam, ASK and Arganosa, G and Daba, K and Caron, C and Lachagari, RVB and Tar'an, B and Warkentin, TD}, title = {Construction of high-density linkage maps for mapping quantitative trait loci for multiple traits in field pea (Pisum sativum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {172}, pmid = {30115030}, issn = {1471-2229}, mesh = {Ascomycota/*physiology ; *Chromosome Mapping ; Disease Resistance/genetics ; *Genetic Linkage ; *Genotype ; Peas/*genetics/physiology ; Phenotype ; Plant Diseases/microbiology ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: The objective of this research was to map quantitative trait loci (QTLs) of multiple traits of breeding importance in pea (Pisum sativum L.). Three recombinant inbred line (RIL) populations, PR-02 (Orb x CDC Striker), PR-07 (Carerra x CDC Striker) and PR-15 (1-2347-144 x CDC Meadow) were phenotyped for agronomic and seed quality traits under field conditions over multiple environments in Saskatchewan, Canada. The mapping populations were genotyped using genotyping-by-sequencing (GBS) method for simultaneous single nucleotide polymorphism (SNP) discovery and construction of high-density linkage maps.

RESULTS: After filtering for read depth, segregation distortion, and missing values, 2234, 3389 and 3541 single nucleotide polymorphism (SNP) markers identified by GBS in PR-02, PR-07 and PR-15, respectively, were used for construction of genetic linkage maps. Genetic linkage groups were assigned by anchoring to SNP markers previously positioned on these linkage maps. PR-02, PR-07 and PR-15 genetic maps represented 527, 675 and 609 non-redundant loci, and cover map distances of 951.9, 1008.8 and 914.2 cM, respectively. Based on phenotyping of the three mapping populations in multiple environments, 375 QTLs were identified for important traits including days to flowering, days to maturity, lodging resistance, Mycosphaerella blight resistance, seed weight, grain yield, acid and neutral detergent fiber concentration, seed starch concentration, seed shape, seed dimpling, and concentration of seed iron, selenium and zinc. Of all the QTLs identified, the most significant in terms of explained percentage of maximum phenotypic variance (PVmax) and occurrence in multiple environments were the QTLs for days to flowering (PVmax = 47.9%), plant height (PVmax = 65.1%), lodging resistance (PVmax = 35.3%), grain yield (PVmax = 54.2%), seed iron concentration (PVmax = 27.4%), and seed zinc concentration (PVmax = 43.2%).

CONCLUSION: We have identified highly significant and reproducible QTLs for several agronomic and seed quality traits of breeding importance in pea. The QTLs identified will be the basis for fine mapping candidate genes, while some of the markers linked to the highly significant QTLs are useful for immediate breeding applications.}, } @article {pmid30115014, year = {2018}, author = {Chou, HC and Acevedo-Luna, N and Kuhlman, JA and Schneider, SQ}, title = {PdumBase: a transcriptome database and research tool for Platynereis dumerilii and early development of other metazoans.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {618}, pmid = {30115014}, issn = {1471-2164}, support = {12-3985//Roy J. Carver Charitable Trust/ ; 1455185//National Science Foundation/ ; }, mesh = {Algorithms ; Animals ; Annelida/classification/genetics ; Biomedical Research/*methods ; Computational Biology/*methods ; *Databases, Genetic ; Embryo, Nonmammalian ; Embryonic Development/*genetics ; Gene Expression Profiling ; Genes, Developmental ; Polychaeta/*embryology/*genetics ; *Transcriptome ; }, abstract = {BACKGROUND: The marine polychaete annelid Platynereis dumerilii has recently emerged as a prominent organism for the study of development, evolution, stem cells, regeneration, marine ecology, chronobiology and neurobiology within metazoans. Its phylogenetic position within the spiralian/ lophotrochozoan clade, the comparatively high conservation of ancestral features in the Platynereis genome, and experimental access to any stage within its life cycle, make Platynereis an important model for elucidating the complex regulatory and functional molecular mechanisms governing early development, later organogenesis, and various features of its larval and adult life. High resolution RNA-seq gene expression data obtained from specific developmental stages can be used to dissect early developmental mechanisms. However, the potential for discovery of these mechanisms relies on tools to search, retrieve, and compare genome-wide information within Platynereis, and across other metazoan taxa.

RESULTS: To facilitate exploration and discovery by the broader scientific community, we have developed a web-based, searchable online research tool, PdumBase, featuring the first comprehensive transcriptome database for Platynereis dumerilii during early stages of development (2 h ~ 14 h). Our database also includes additional stages over the P. dumerilii life cycle and provides access to the expression data of 17,213 genes (31,806 transcripts) along with annotation information sourced from Swiss-Prot, Gene Ontology, KEGG pathways, Pfam domains, TmHMM, SingleP, and EggNOG orthology. Expression data for each gene includes the stage, the normalized FPKM, the raw read counts, and information that can be leveraged for statistical analyses of differential gene expression and the construction of genome-wide co-expression networks. In addition, PdumBase offers early stage transcriptome expression data from five further species as a valuable resource for investigators interested in comparing early development in different organisms. To understand conservation of Platynereis gene models and to validate gene annotation, most Platynereis gene models include a comprehensive phylogenetic analysis across 18 species representing diverse metazoan taxa.

CONCLUSIONS: PdumBase represents the first online resource for the early developmental transcriptome of Platynereis dumerilii. It serves as a research platform for discovery and exploration of gene expression during early stages, throughout the Platynereis life cycle, and enables comparison to other model organisms. PdumBase is freely available at http://pdumbase.gdcb.iastate.edu .}, } @article {pmid30115012, year = {2018}, author = {Loewen, PC and Switala, J and Wells, JP and Huang, F and Zara, AT and Allingham, JS and Loewen, MC}, title = {Structure and function of a lignostilbene-α,β-dioxygenase orthologue from Pseudomonas brassicacearum.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {8}, pmid = {30115012}, issn = {1471-2091}, support = {007847//National Research Council of Canada/International ; 356025-2013//Natural Sciences and Engineering Research Council of Canada/International ; 9600-2012//Natural Sciences and Engineering Research Council of Canada/International ; 261683-2012//Natural Sciences and Engineering Research Council of Canada/International ; Structural Biology//Canadian Research Chair/International ; Protein Chemistry//Canadian Research Chair/International ; }, mesh = {Crystallography, X-Ray ; Dioxygenases/*chemistry/classification/*metabolism ; Molecular Docking Simulation ; Phylogeny ; Protein Conformation ; Pseudomonas/*enzymology ; Recombinant Proteins/chemistry/metabolism ; Reproducibility of Results ; Soil Microbiology ; Substrate Specificity ; }, abstract = {BACKGROUND: Stilbene cleaving oxygenases (SCOs), also known as lignostilbene-α,β-dioxygenases (LSDs) mediate the oxidative cleavage of the olefinic double bonds of lignin-derived intermediate phenolic stilbenes, yielding small modified benzaldehyde compounds. SCOs represent one branch of the larger carotenoid cleavage oxygenases family. Here, we describe the structural and functional characterization of an SCO-like enzyme from the soil-born, bio-control agent Pseudomonas brassicacearum.

METHODS: In vitro and in vivo assays relying on visual inspection, spectrophotometric quantification, as well as liquid-chormatographic and mass spectrometric characterization were applied for functional evaluation of the enzyme. X-ray crystallographic analyses and in silico modeling were applied for structural investigations.

RESULTS: In vitro assays demonstrated preferential cleavage of resveratrol, while in vivo analyses detected putative cleavage of the straight chain carotenoid, lycopene. A high-resolution structure containing the seven-bladed β-propeller fold and conserved 4-His-Fe unit at the catalytic site, was obtained. Comparative structural alignments, as well as in silico modelling and docking, highlight potential molecular factors contributing to both the primary in vitro activity against resveratrol, as well as the putative subsidiary activities against carotenoids in vivo, for future validation.

CONCLUSIONS: The findings reported here provide validation of the SCO structure, and highlight enigmatic points with respect to the potential effect of the enzyme's molecular environment on substrate specificities for future investigation.}, } @article {pmid30115009, year = {2018}, author = {Vanmechelen, B and Bletsa, M and Laenen, L and Lopes, AR and Vergote, V and Beller, L and Deboutte, W and Korva, M and Avšič Županc, T and Goüy de Bellocq, J and Gryseels, S and Leirs, H and Lemey, P and Vrancken, B and Maes, P}, title = {Discovery and genome characterization of three new Jeilongviruses, a lineage of paramyxoviruses characterized by their unique membrane proteins.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {617}, pmid = {30115009}, issn = {1471-2164}, support = {1S28617N//Fonds Wetenschappelijk Onderzoek/ ; 1S61618N//Fonds Wetenschappelijk Onderzoek/ ; 12T1117N//Fonds Wetenschappelijk Onderzoek/ ; 1167112N//Fonds Wetenschappelijk Onderzoek/ ; 12U7118N//Fonds Wetenschappelijk Onderzoek/ ; G066215N//Fonds Wetenschappelijk Onderzoek/ ; G0D5117N//Fonds Wetenschappelijk Onderzoek/ ; G0B9317N//Fonds Wetenschappelijk Onderzoek/ ; P3-0083//Javna Agencija za Raziskovalno Dejavnost RS/ ; P506-10-0983//Grantová Agentura České Republiky/ ; 653316//H2020 European Research Council/ ; 725422//H2020 European Research Council/ ; }, mesh = {Amino Acid Sequence ; Animals ; Cloning, Molecular ; *Genome, Viral ; Membrane Proteins/*genetics ; Paramyxoviridae/classification/genetics ; Paramyxovirinae/*classification/*genetics ; Phylogeny ; Sequence Analysis, DNA ; Viral Proteins/*genetics ; }, abstract = {BACKGROUND: In the past decade, many new paramyxoviruses that do not belong to any of the seven established genera in the family Paramyxoviridae have been discovered. Amongst them are J-virus (JPV), Beilong virus (BeiPV) and Tailam virus (TlmPV), three paramyxovirus species found in rodents. Based on their similarities, it has been suggested that these viruses should compose a new genus, tentatively called 'Jeilongvirus'.

RESULTS: Here we present the complete genomes of three newly discovered paramyxoviruses, one found in a bank vole (Myodes glareolus) from Slovenia and two in a single, co-infected Rungwe brush-furred rat (Lophuromys machangui) from Mozambique, that represent three new, separate species within the putative genus 'Jeilongvirus'. The genome organization of these viruses is similar to other paramyxoviruses, but like JPV, BeiPV and TlmPV, they possess an additional open reading frame, encoding a transmembrane protein, that is located between the F and G genes. As is the case for all Jeilongviruses, the G genes of the viruses described here are unusually large, and their encoded proteins are characterized by a remarkable amino acid composition pattern that is not seen in other paramyxoviruses, but resembles certain motifs found in Orthopneumovirus G proteins.

CONCLUSIONS: The phylogenetic clustering of JPV, BeiPV and TlmPV with the viruses described here, as well as their shared features that set them apart from other paramyxoviruses, provide additional support for the recognition of the genus 'Jeilongvirus'.}, } @article {pmid30113887, year = {2018}, author = {Grant, CR and Wan, J and Komeili, A}, title = {Organelle Formation in Bacteria and Archaea.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {217-238}, doi = {10.1146/annurev-cellbio-100616-060908}, pmid = {30113887}, issn = {1530-8995}, support = {R01 GM084122/GM/NIGMS NIH HHS/United States ; R35 GM127114/GM/NIGMS NIH HHS/United States ; }, abstract = {Uncovering the mechanisms that underlie the biogenesis and maintenance of eukaryotic organelles is a vibrant and essential area of biological research. In comparison, little attention has been paid to the process of compartmentalization in bacteria and archaea. This lack of attention is in part due to the common misconception that organelles are a unique evolutionary invention of the "complex" eukaryotic cell and are absent from the "primitive" bacterial and archaeal cells. Comparisons across the tree of life are further complicated by the nebulous criteria used to designate subcellular structures as organelles. Here, with the aid of a unified definition of a membrane-bounded organelle, we present some of the recent findings in the study of lipid-bounded organelles in bacteria and archaea.}, } @article {pmid30113695, year = {2018}, author = {Woerner, AE and Veeramah, KR and Watkins, JC and Hammer, MF}, title = {The role of phylogenetically conserved elements in shaping patterns of human genomic diversity.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {30113695}, issn = {1537-1719}, abstract = {Evolutionary genetic studies have shown a positive correlation between levels of nucleotide diversity and either rates of recombination or genetic distance to genes. Both positive-directional and purifying selection have been offered as the source of these correlations via genetic hitchhiking and background selection, respectively. Phylogenetically conserved elements (CEs) are short (∼100bp), widely distributed (comprising ∼5% of genome), sequences that are often found far from genes. While the function of many CEs is unknown, CEs also are associated with reduced diversity at linked sites. Using high coverage (>80x) whole genome data from two human populations, the Yoruba and the CEU, we perform fine scale evaluations of diversity, rates of recombination, and linkage to genes. We find that the local rate of recombination has a stronger effect on levels of diversity than linkage to genes, and that these effects of recombination persist even in regions far from genes. Our whole genome modeling demonstrates that, rather than recombination or GC-biased gene conversion, selection on sites within or linked to CEs better explains the observed genomic diversity patterns. A major implication is that very few sites in the human genome are predicted to be free of the effects of selection. These sites, which we refer to as the human "neutralome", comprise only 1.2% of the autosomes and 5.1% of the X chromosome. Demographic analysis of the neutralome reveals larger population sizes and lower rates of growth for ancestral human populations than inferred by previous analyses.}, } @article {pmid30113623, year = {2018}, author = {Krasovec, M and Vancaester, E and Rombauts, S and Bucchini, F and Yau, S and Hemon, C and Lebredonchel, H and Grimsley, N and Moreau, H and Sanchez-Brosseau, S and Vandepoele, K and Piganeau, G}, title = {Genome Analyses of the Microalga Picochlorum Provide Insights into the Evolution of Thermotolerance in the Green Lineage.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2347-2365}, pmid = {30113623}, issn = {1759-6653}, abstract = {While the molecular events involved in cell responses to heat stress have been extensively studied, our understanding of the genetic basis of basal thermotolerance, and particularly its evolution within the green lineage, remains limited. Here, we present the 13.3-Mb haploid genome and transcriptomes of a halotolerant and thermotolerant unicellular green alga, Picochlorum costavermella (Trebouxiophyceae) to investigate the evolution of the genomic basis of thermotolerance. Differential gene expression at high and standard temperatures revealed that more of the gene families containing up-regulated genes at high temperature were recently evolved, and less originated at the ancestor of green plants. Inversely, there was an excess of ancient gene families containing transcriptionally repressed genes. Interestingly, there is a striking overlap between the thermotolerance and halotolerance transcriptional rewiring, as more than one-third of the gene families up-regulated at 35 °C were also up-regulated under variable salt concentrations in Picochlorum SE3. Moreover, phylogenetic analysis of the 9,304 protein coding genes revealed 26 genes of horizontally transferred origin in P. costavermella, of which five were differentially expressed at higher temperature. Altogether, these results provide new insights about how the genomic basis of adaptation to halo- and thermotolerance evolved in the green lineage.}, } @article {pmid30113302, year = {2018}, author = {Oren, A and Garrity, G}, title = {Proposal to emend Rules 50a and 50b of the International Code of Nomenclature of Prokaryotes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {3371-3376}, doi = {10.1099/ijsem.0.002958}, pmid = {30113302}, issn = {1466-5034}, abstract = {Rules 50a and 50b of the International Code of Nomenclature of Prokaryotes respectively regulate the elevation of a subspecies to the rank of a species and the lowering of a species to the rank of subspecies. The Code does not indicate that the resulting new names must be considered new combinations, as the cases described in Rules 50a and 50b are not covered by Rule 34a. Based on the rules of the Code, new combination events are applicable only at the identical rank, and therefore new combination events and new species/subspecies events are mutually exclusive. In spite of this there have been at least 44 cases in which the new names were described as comb. nov. during elevation in rank from subspecies to species and at least 30 such cases during lowering in rank from species to subspecies. To prevent confusion in the future we propose adding notes to Rules 50a and 50b to clarify the issue.}, } @article {pmid30113301, year = {2018}, author = {Choi, S and Lee, JH and Kang, JW and Choe, HN and Seong, CN}, title = {Flagellimonas aquimarina sp. nov., and transfer of Spongiibacterium flavum Yoon and Oh 2012 and S. pacificum Gao et al. 2015 to the genus Flagellimonas Bae et al. 2007 as Flagellimonas flava comb. nov. and F. pacifica comb. nov., respectively.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3266-3272}, doi = {10.1099/ijsem.0.002975}, pmid = {30113301}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phaeophyta/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seaweed/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-spore-forming, rod-shaped, aerobic and diffusible yellow-coloured bacterial strain, designated strain ECD12T was isolated from a seaweed, Ecklonia cava. The isolate required sea salts for growth. Catalase-positive and oxidase-negative. A phylogenetic tree based on 16S rRNA gene sequences showed that strain ECD12T formed an evolutionary lineage within the radiation enclosing the members of genera Spongiibacterium and Flagellimonas sharing the highest similarity to Flagellimonas eckloniae DOKDO007T (96.8 % 16S rRNA gene sequence similarity) followed by Spongiibacterium pacificum SW169T (96.4 %) and Spongiibacterium flavum DSM 22638T (96.1 %). The major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1 G. The new isolate contained MK-6 as the only isoprenoid quinone and phosphatidylethanolamine, two unidentified amino lipids and two unidentified lipids as the major polar lipids. The genomic DNA G+C content is 39 mol%. A number of phenotypic characteristics such as the production of diffusible pigment distinguished strain ECD12T from the related species. On the basis of the evidence presented in this study, a novel species, Flagellimonas aquimarina sp. nov., is proposed for strain ECD12T (=KCTC 52351T=JCM 32292T). Based on the sequence similarity, phylogenetic relationship and common morphological, physiological and chemical characters among the members of the genera Spongiibacterium and Flagellimonas, it is recommended that the two genera are combined into a single genus. Thus, transfer of S. flavumYoon and Oh 2012 and S. pacificum Gao et al. 2015 to the genus FlagellimonasBae et al. 2007 as Flagellimonas flava comb. nov. and Flagellimonas pacifica comb. nov., respectively, is also proposed.}, } @article {pmid30113300, year = {2018}, author = {Garcia, R and Müller, R}, title = {Simulacricoccus ruber gen. nov., sp. nov., a microaerotolerant, non-fruiting, myxospore-forming soil myxobacterium and emended description of the family Myxococcaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3101-3110}, doi = {10.1099/ijsem.0.002936}, pmid = {30113300}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Germany ; Myxococcales/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A non-fruiting group of myxobacteria was previously speculated to exist in nature based on metagenomics data containing uncultured members of the order Myxococcales. Here, we describe a myxobacterial strain, designated MCy10636T, which was isolated from a German soil sample collected in 2013. It exhibits swarming characteristics but atypically produces myxospores in the absence of fruiting bodies. The novel strain stains Gram-negative and Congo-red-negative and is characterized mesophilic, neutrophilic, chemoheterotrophic and microaerotolerant. Branched-chain fatty acids are the predominant cellular fatty acids over the straight-chain type, and contain the major fatty acids iso-C17 : 0 2-OH, C16 : 1, iso-C17 : 0 and iso-C15 : 0. Based on blastn results, the 16S rRNA gene sequence reveals similarity (97 %) to Aggregicoccus edonensis MCy1366T, (97 %) Myxococcus macrosporus DSM 14697T, (96 %) Corallococcus coralloides DSM2259T and Corallococcus exiguus Cc e167T. Phylogenetic analysis showed a novel lineage of MCy10636T in the family Myxococcaceae, suborder Cystobacterineae. Based on polyphasic taxonomic characterization, we propose that this unusual, non-fruiting, myxospore-forming and microaerotolerant myxobacterial strain, MCy10636T, represents a novel genus and species, Simulacricoccus ruber gen. nov., sp. nov. (DSM 106554T=NCCB 100651T).}, } @article {pmid30113299, year = {2018}, author = {Yang, L and Muhadesi, JB and Wang, MM and Wang, BJ and Liu, SJ and Jiang, CY}, title = {Thauera hydrothermalis sp. nov., a thermophilic bacterium isolated from hot spring.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3163-3168}, doi = {10.1099/ijsem.0.002960}, pmid = {30113299}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hot Springs/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Thauera/*classification/genetics/isolation & purification ; Tibet ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, non-spore-forming, rod-shaped, motile bacterial strain, designated GD-2T, was isolated from a sediment sample collected from a hot spring in the Tibet Autonomous Region, China. Strain GD-2T grew at a temperature range of 37-55 °C (optimum, 45-50 °C), a pH range of 5.5-11.0 (pH 7.0-7.5) and a NaCl concentration range of 0-4.0 % (0 %). The phylogenetic analysis based on 16S rRNA gene sequencing showed that strain GD-2T represented a member of the genus Thauera within the family Zoogloeaceae. Strain GD-2T was closely related to Thauera linaloolentis 47LolT with the highest 16S rRNA gene sequence similarity of 95.5 %. The whole genomic average nucleotide identity value for GD-2T and 47LolT was 75.3 %. The predominant cellular fatty acids of the strain were C16 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), C10 : 0 3-OH and C12 : 0. The main polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids and two unidentified aminolipids. The major isoprenoid quinone was ubiquinone 8. Genome sequencing revealed that the genome size of GD-2T was 3 059 321 bp with a G+C content of 63.57 mol%. On the basis of phylogenetic, phenotypic and chemotaxonomic characteristics, strain GD-2T is considered to represent a novel species of the genus Thauera, for which the name Thauera hydrothermalis sp. nov. is proposed. The type strain is GD-2T (=NBRC 112472T=CGMCC 1.15527T).}, } @article {pmid30113296, year = {2018}, author = {Yu, Y and Hou, SY and Sun, ZL and Zhang, MY and Zhang, TY and Zhang, YX}, title = {Drechmeria panacis sp. nov., an endophyte isolated from Panax notoginseng.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3255-3259}, doi = {10.1099/ijsem.0.002971}, pmid = {30113296}, issn = {1466-5034}, mesh = {China ; DNA, Fungal ; Endophytes/classification/genetics/isolation & purification ; Hypocreales/*classification/genetics/isolation & purification ; Mycological Typing Techniques ; Panax notoginseng/*microbiology ; *Phylogeny ; Plant Roots/*microbiology ; Sequence Analysis, DNA ; }, abstract = {An endophytic strain (designated as strain SYPF 8335T) was isolated from a root of Panax notoginseng in Wenshan district, Yunnan province of China. Strain SYPF 8335T grew very slowly and formed white colonies. Phylogenetic analysis of four loci indicated that strain SYPF 8335T was placed in the Drechmeria clade with Drechmeria campanulata as its closest phylogenetic neighbour. The nucleotide differences between strain SYPF 8335T and D. campanulata are 30 substitutions in the internal transcriber region region. A key morphological feature that differentiates the two fungi is that D. campanulata produces campanulate conidia. Combined with the morphology and molecular analyses, a new species named Drechmeria panacis sp. nov., is proposed.}, } @article {pmid30113099, year = {2018}, author = {Stelbrink, B and Jovanovska, E and Levkov, Z and Ognjanova-Rumenova, N and Wilke, T and Albrecht, C}, title = {Diatoms do radiate: evidence for a freshwater species flock.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {12}, pages = {1969-1975}, doi = {10.1111/jeb.13368}, pmid = {30113099}, issn = {1420-9101}, abstract = {Due to the ubiquity and high dispersal capacity of unicellular eukaryotes, their often extraordinary diversity found in isolated and long-lived ecosystems such as ancient lakes is typically attributed to multiple colonization events rather than to in situ speciation. However, respective evolutionary studies are very scarce and the often high number of species flocks in ancient lakes across multicellular taxa raises the question whether unicellular species, such as diatoms, may radiate as well. Here, we use an integrative approach that includes molecular data from benthic diatom species of the genus Aneumastus endemic to ancient Lake Ohrid, fossil data obtained from the sediment record of a recent deep-drilling project and biogeographical information to test if this group, indeed, constitutes a species flock. Molecular-clock and phylogenetic analyses indicate a young monophyletic group of several endemic species. Molecular, fossil and biogeographical data strongly suggest a rapid intralacustrine diversification, which was possibly triggered by the emergence of novel habitats. This finding is the first evidence for a species flock in diatoms and suggests that in situ speciation is also a relevant evolutionary process for unicellular eukaryotes in isolated ecosystems.}, } @article {pmid30112427, year = {2018}, author = {Grossman, M}, title = {Linguistic Aspects of Primary Progressive Aphasia.}, journal = {Annual review of linguistics}, volume = {4}, number = {}, pages = {377-403}, pmid = {30112427}, issn = {2333-9683}, support = {P01 AG017586/AG/NIA NIH HHS/United States ; R01 AG054519/AG/NIA NIH HHS/United States ; U01 AG052943/AG/NIA NIH HHS/United States ; }, abstract = {Primary progressive aphasia (PPA) refers to a disorder of declining language associated with neurodegenerative diseases such as frontotemporal degeneration and Alzheimer disease. Variants of PPA are important to recognize from a medical perspective because these syndromes are clinical markers suggesting specific underlying pathology. In this review, I discuss linguistic aspects of PPA syndromes that may prove informative for parsing our language mechanism and identifying the neural representation of fundamental elements of language. I focus on the representation of word meaning in a discussion of semantic variant PPA, grammatical comprehension and expression in a discussion of nonfluent/agrammatic variant PPA, the supporting role of short-term memory in a discussion of logopenic variant PPA, and components of language associated with discourse in a discussion of behavioral variant frontotemporal dementia. PPA provides a novel perspective that uniquely addresses facets of language and its disorders while complementing traditional aphasia syndromes that follow stroke.}, } @article {pmid30111842, year = {2018}, author = {Yao, K and Qiu, S and Wang, YV and Park, SJH and Mohns, EJ and Mehta, B and Liu, X and Chang, B and Zenisek, D and Crair, MC and Demb, JB and Chen, B}, title = {Restoration of vision after de novo genesis of rod photoreceptors in mammalian retinas.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {484-488}, pmid = {30111842}, issn = {1476-4687}, support = {R01 EY019943/EY/NEI NIH HHS/United States ; R01 EY021502/EY/NEI NIH HHS/United States ; R01 EY024986/EY/NEI NIH HHS/United States ; R01 EY015788/EY/NEI NIH HHS/United States ; R01 EY014454/EY/NEI NIH HHS/United States ; R01 EY021372/EY/NEI NIH HHS/United States ; R01 EY023105/EY/NEI NIH HHS/United States ; R01 EY021195/EY/NEI NIH HHS/United States ; R01 EY014990/EY/NEI NIH HHS/United States ; P30 EY026878/EY/NEI NIH HHS/United States ; }, abstract = {In zebrafish, Müller glia (MG) are a source of retinal stem cells that can replenish damaged retinal neurons and restore vision1. In mammals, however, MG do not spontaneously re-enter the cell cycle to generate a population of stem or progenitor cells that differentiate into retinal neurons. Nevertheless, the regenerative machinery may exist in the mammalian retina, as retinal injury can stimulate MG proliferation followed by limited neurogenesis2-7. Therefore, there is still a fundamental question regarding whether MG-derived regeneration can be exploited to restore vision in mammalian retinas. Gene transfer of β-catenin stimulates MG proliferation in the absence of injury in mouse retinas8. Here we report that following gene transfer of β-catenin, cell-cycle-reactivated MG can be reprogrammed to generate rod photoreceptors by subsequent gene transfer of transcription factors essential for rod cell fate specification and determination. MG-derived rods restored visual responses in Gnat1rd17Gnat2cpfl3 double mutant mice, a model of congenital blindness9,10, throughout the visual pathway from the retina to the primary visual cortex. Together, our results provide evidence of vision restoration after de novo MG-derived genesis of rod photoreceptors in mammalian retinas.}, } @article {pmid30111841, year = {2018}, author = {Li, S and Tian, Y and Wu, K and Ye, Y and Yu, J and Zhang, J and Liu, Q and Hu, M and Li, H and Tong, Y and Harberd, NP and Fu, X}, title = {Modulating plant growth-metabolism coordination for sustainable agriculture.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {595-600}, pmid = {30111841}, issn = {1476-4687}, abstract = {Enhancing global food security by increasing the productivity of green revolution varieties of cereals risks increasing the collateral environmental damage produced by inorganic nitrogen fertilizers. Improvements in the efficiency of nitrogen use of crops are therefore essential; however, they require an in-depth understanding of the co-regulatory mechanisms that integrate growth, nitrogen assimilation and carbon fixation. Here we show that the balanced opposing activities and physical interactions of the rice GROWTH-REGULATING FACTOR 4 (GRF4) transcription factor and the growth inhibitor DELLA confer homeostatic co-regulation of growth and the metabolism of carbon and nitrogen. GRF4 promotes and integrates nitrogen assimilation, carbon fixation and growth, whereas DELLA inhibits these processes. As a consequence, the accumulation of DELLA that is characteristic of green revolution varieties confers not only yield-enhancing dwarfism, but also reduces the efficiency of nitrogen use. However, the nitrogen-use efficiency of green revolution varieties and grain yield are increased by tipping the GRF4-DELLA balance towards increased GRF4 abundance. Modulation of plant growth and metabolic co-regulation thus enables novel breeding strategies for future sustainable food security and a new green revolution.}, } @article {pmid30111840, year = {2018}, author = {Parras, A and Anta, H and Santos-Galindo, M and Swarup, V and Elorza, A and Nieto-González, JL and Picó, S and Hernández, IH and Díaz-Hernández, JI and Belloc, E and Rodolosse, A and Parikshak, NN and Peñagarikano, O and Fernández-Chacón, R and Irimia, M and Navarro, P and Geschwind, DH and Méndez, R and Lucas, JJ}, title = {Autism-like phenotype and risk gene mRNA deadenylation by CPEB4 mis-splicing.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {441-446}, pmid = {30111840}, issn = {1476-4687}, support = {F30 MH099886/MH/NIMH NIH HHS/United States ; R01 MH100027/MH/NIMH NIH HHS/United States ; R37 MH060233/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/*genetics/*pathology ; Brain/metabolism/pathology ; Exons/genetics ; Female ; Genetic Predisposition to Disease/*genetics ; Humans ; Male ; Mice ; Mice, Transgenic ; Neurons/metabolism ; Phenotype ; *Polyadenylation ; Protein Binding ; *RNA Splicing ; RNA, Messenger/chemistry/genetics/*metabolism ; RNA-Binding Proteins/*genetics/*metabolism ; Transcriptome ; }, abstract = {Common genetic contributions to autism spectrum disorder (ASD) reside in risk gene variants that individually have minimal effect sizes. As environmental factors that perturb neurodevelopment also underlie idiopathic ASD, it is crucial to identify altered regulators that can orchestrate multiple ASD risk genes during neurodevelopment. Cytoplasmic polyadenylation element binding proteins 1-4 (CPEB1-4) regulate the translation of specific mRNAs by modulating their poly(A)-tails and thereby participate in embryonic development and synaptic plasticity. Here we find that CPEB4 binds transcripts of most high-confidence ASD risk genes. The brains of individuals with idiopathic ASD show imbalances in CPEB4 transcript isoforms that result from decreased inclusion of a neuron-specific microexon. In addition, 9% of the transcriptome shows reduced poly(A)-tail length. Notably, this percentage is much higher for high-confidence ASD risk genes, correlating with reduced expression of the protein products of ASD risk genes. An equivalent imbalance in CPEB4 transcript isoforms in mice mimics the changes in mRNA polyadenylation and protein expression of ASD risk genes and induces ASD-like neuroanatomical, electrophysiological and behavioural phenotypes. Together, these data identify CPEB4 as a regulator of ASD risk genes.}, } @article {pmid30111839, year = {2018}, author = {Butterwick, JA and Del Mármol, J and Kim, KH and Kahlson, MA and Rogow, JA and Walz, T and Ruta, V}, title = {Cryo-EM structure of the insect olfactory receptor Orco.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {447-452}, pmid = {30111839}, issn = {1476-4687}, support = {R01 AI103171/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Animals ; Binding Sites ; Conserved Sequence ; *Cryoelectron Microscopy ; Hydrophobic and Hydrophilic Interactions ; Immunoglobulin Fab Fragments/chemistry/ultrastructure ; Insecta/chemistry/classification/*ultrastructure ; Ion Channel Gating ; Models, Molecular ; Phylogeny ; Protein Multimerization ; Protein Structure, Quaternary ; Receptors, Odorant/*chemistry/metabolism/*ultrastructure ; Sequence Alignment ; }, abstract = {The olfactory system must recognize and discriminate amongst an enormous variety of chemicals in the environment. To contend with such diversity, insects have evolved a family of odorant-gated ion channels comprised of a highly conserved co-receptor (Orco) and a divergent odorant receptor (OR) that confers chemical specificity. Here, we present the single-particle cryo-electron microscopy structure of an Orco homomer from the parasitic fig wasp Apocrypta bakeri at 3.5 Å resolution, providing structural insight into this receptor family. Orco possesses a novel channel architecture, with four subunits symmetrically arranged around a central pore that diverges into four lateral conduits that open to the cytosol. The Orco tetramer has few inter-subunit interactions within the membrane and is bound together by a small cytoplasmic anchor domain. The minimal sequence conservation among ORs maps largely to the pore and anchor domain, shedding light on how the architecture of this receptor family accommodates its remarkable sequence diversity and facilitates the evolution of odour tuning.}, } @article {pmid30111838, year = {2018}, author = {Hoeijmakers, HJ and Ehrenreich, D and Heng, K and Kitzmann, D and Grimm, SL and Allart, R and Deitrick, R and Wyttenbach, A and Oreshenko, M and Pino, L and Rimmer, PB and Molinari, E and Di Fabrizio, L}, title = {Atomic iron and titanium in the atmosphere of the exoplanet KELT-9b.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {453-455}, doi = {10.1038/s41586-018-0401-y}, pmid = {30111838}, issn = {1476-4687}, abstract = {To constrain the formation history of an exoplanet, we need to know its chemical composition1-3. With an equilibrium temperature of about 4,050 kelvin4, the exoplanet KELT-9b (also known as HD 195689b) is an archetype of the class of ultrahot Jupiters that straddle the transition between stars and gas-giant exoplanets and are therefore useful for studying atmospheric chemistry. At these high temperatures, iron and several other transition metals are not sequestered in molecules or cloud particles and exist solely in their atomic forms5. However, despite being the most abundant transition metal in nature, iron has not hitherto been detected directly in an exoplanet because it is highly refractory. The high temperatures of KELT-9b imply that its atmosphere is a tightly constrained chemical system that is expected to be nearly in chemical equilibrium5 and cloud-free6,7, and it has been predicted that spectral lines of iron should be detectable in the visible range of wavelengths5. Here we report observations of neutral and singly ionized atomic iron (Fe and Fe+) and singly ionized atomic titanium (Ti+) in the atmosphere of KELT-9b. We identify these species using cross-correlation analysis8 of high-resolution spectra obtained as the exoplanet passed in front of its host star. Similar detections of metals in other ultrahot Jupiters will provide constraints for planetary formation theories.}, } @article {pmid30111837, year = {2018}, author = {Siviter, H and Brown, MJF and Leadbeater, E}, title = {Sulfoxaflor exposure reduces bumblebee reproductive success.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {109-112}, doi = {10.1038/s41586-018-0430-6}, pmid = {30111837}, issn = {1476-4687}, abstract = {Intensive agriculture currently relies on pesticides to maximize crop yield1,2. Neonicotinoids are the most widely used insecticides globally3, but increasing evidence of negative impacts on important pollinators4-9 and other non-target organisms10 has led to legislative reassessment and created demand for the development of alternative products. Sulfoximine-based insecticides are the most likely successor11, and are either licensed for use or under consideration for licensing in several worldwide markets3, including within the European Union12, where certain neonicotinoids (imidacloprid, clothianidin and thiamethoxam) are now banned from agricultural use outside of permanent greenhouse structures. There is an urgent need to pre-emptively evaluate the potential sub-lethal effects of sulfoximine-based pesticides on pollinators11, because such effects are rarely detected by standard ecotoxicological assessments, but can have major impacts at larger ecological scales13-15. Here we show that chronic exposure to the sulfoximine-based insecticide sulfoxaflor, at dosages consistent with potential post-spray field exposure, has severe sub-lethal effects on bumblebee (Bombus terrestris) colonies. Field-based colonies that were exposed to sulfoxaflor during the early growth phase produced significantly fewer workers than unexposed controls, and ultimately produced fewer reproductive offspring. Differences between the life-history trajectories of treated and control colonies first became apparent when individuals exposed as larvae began to emerge, suggesting that direct or indirect effects on a small cohort may have cumulative long-term consequences for colony fitness. Our results caution against the use of sulfoximines as a direct replacement for neonicotinoids. To avoid continuing cycles of novel pesticide release and removal, with concomitant impacts on the environment, a broad evidence base needs to be assessed prior to the development of policy and regulation.}, } @article {pmid30111836, year = {2018}, author = {Zhou, P and She, Y and Dong, N and Li, P and He, H and Borio, A and Wu, Q and Lu, S and Ding, X and Cao, Y and Xu, Y and Gao, W and Dong, M and Ding, J and Wang, DC and Zamyatina, A and Shao, F}, title = {Alpha-kinase 1 is a cytosolic innate immune receptor for bacterial ADP-heptose.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {122-126}, doi = {10.1038/s41586-018-0433-3}, pmid = {30111836}, issn = {1476-4687}, abstract = {Immune recognition of pathogen-associated molecular patterns (PAMPs) by pattern recognition receptors often activates proinflammatory NF-κB signalling1. Recent studies indicate that the bacterial metabolite D-glycero-β-D-manno-heptose 1,7-bisphosphate (HBP) can activate NF-κB signalling in host cytosol2-4, but it is unclear whether HBP is a genuine PAMP and the cognate pattern recognition receptor has not been identified. Here we combined a transposon screen in Yersinia pseudotuberculosis with biochemical analyses and identified ADP-β-D-manno-heptose (ADP-Hep), which mediates type III secretion system-dependent NF-κB activation and cytokine expression. ADP-Hep, but not other heptose metabolites, could enter host cytosol to activate NF-κB. A CRISPR-Cas9 screen showed that activation of NF-κB by ADP-Hep involves an ALPK1 (alpha-kinase 1)-TIFA (TRAF-interacting protein with forkhead-associated domain) axis. ADP-Hep directly binds the N-terminal domain of ALPK1, stimulating its kinase domain to phosphorylate and activate TIFA. The crystal structure of the N-terminal domain of ALPK1 and ADP-Hep in complex revealed the atomic mechanism of this ligand-receptor recognition process. HBP was transformed by host adenylyltransferases into ADP-heptose 7-P, which could activate ALPK1 to a lesser extent than ADP-Hep. ADP-Hep (but not HBP) alone or during bacterial infection induced Alpk1-dependent inflammation in mice. Our findings identify ALPK1 and ADP-Hep as a pattern recognition receptor and an effective immunomodulator, respectively.}, } @article {pmid30111830, year = {2018}, author = {Salzburger, W}, title = {Understanding explosive diversification through cichlid fish genomics.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {11}, pages = {705-717}, doi = {10.1038/s41576-018-0043-9}, pmid = {30111830}, issn = {1471-0064}, abstract = {Owing to their taxonomic, phenotypic, ecological and behavioural diversity and propensity for explosive diversification, the assemblages of cichlid fish in the East African Great Lakes Victoria, Malawi and Tanganyika are important role models in evolutionary biology. With the release of five reference genomes and many additional genomic resources, as well as the establishment of functional genomic tools, the cichlid system has fully entered the genomic era. The in-depth genomic exploration of the East African cichlid fauna - in combination with the examination of their ecology, morphology and behaviour - permits novel insights into the way organisms diversify.}, } @article {pmid30111793, year = {2018}, author = {Else, H}, title = {How Unpaywall is transforming open science.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {290-291}, doi = {10.1038/d41586-018-05968-3}, pmid = {30111793}, issn = {1476-4687}, } @article {pmid30111792, year = {2018}, author = {}, title = {Plagiarism rules, discrimination settlements and asteroid close-up.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {286-287}, doi = {10.1038/d41586-018-05938-9}, pmid = {30111792}, issn = {1476-4687}, } @article {pmid30111791, year = {2018}, author = {Armstrong, JW}, title = {The preprint.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {404}, doi = {10.1038/d41586-018-05945-w}, pmid = {30111791}, issn = {1476-4687}, } @article {pmid30111790, year = {2018}, author = {Litman, ZC and Wang, Y and Zhao, H and Hartwig, JF}, title = {Cooperative asymmetric reactions combining photocatalysis and enzymatic catalysis.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {355-359}, doi = {10.1038/s41586-018-0413-7}, pmid = {30111790}, issn = {1476-4687}, support = {DE-SC0018420//Department of Energy/International ; }, abstract = {Living organisms rely on simultaneous reactions catalysed by mutually compatible and selective enzymes to synthesize complex natural products and other metabolites. To combine the advantages of these biological systems with the reactivity of artificial chemical catalysts, chemists have devised sequential, concurrent, and cooperative chemoenzymatic reactions that combine enzymatic and artificial catalysts1-9. Cooperative chemoenzymatic reactions consist of interconnected processes that generate products in yields and selectivities that cannot be obtained when the two reactions are carried out sequentially with their respective substrates2,7. However, such reactions are difficult to develop because chemical and enzymatic catalysts generally operate in different media at different temperatures and can deactivate each other1-9. Owing to these constraints, the vast majority of cooperative chemoenzymatic processes that have been reported over the past 30 years can be divided into just two categories: chemoenzymatic dynamic kinetic resolutions of racemic alcohols and amines, and enzymatic reactions requiring the simultaneous regeneration of a cofactor2,4,5. New approaches to the development of chemoenzymatic reactions are needed to enable valuable chemical transformations beyond this scope. Here we report a class of cooperative chemoenzymatic reaction that combines photocatalysts that isomerize alkenes with ene-reductases that reduce carbon-carbon double bonds to generate valuable enantioenriched products. This method enables the stereoconvergent reduction of E/Z mixtures of alkenes or reduction of the unreactive stereoisomers of alkenes in yields and enantiomeric excesses that match those obtained from the reduction of the pure, more reactive isomers. The system affords a range of enantioenriched precursors to biologically active compounds. More generally, these results show that the compatibility between photocatalysts and enzymes enables chemoenzymatic processes beyond cofactor regeneration and provides a general strategy for converting stereoselective enzymatic reactions into stereoconvergent ones.}, } @article {pmid30111789, year = {2018}, author = {Zachman, MJ and Tu, Z and Choudhury, S and Archer, LA and Kourkoutis, LF}, title = {Cryo-STEM mapping of solid-liquid interfaces and dendrites in lithium-metal batteries.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {345-349}, doi = {10.1038/s41586-018-0397-3}, pmid = {30111789}, issn = {1476-4687}, abstract = {Solid-liquid interfaces are important in a range of chemical, physical and biological processes1-4, but are often not fully understood owing to the lack of high-resolution characterization methods that are compatible with both solid and liquid components5. For example, the related processes of dendritic deposition of lithium metal and the formation of solid-electrolyte interphase layers6,7 are known to be key determinants of battery safety and performance in high-energy-density lithium-metal batteries. But exactly what is involved in these two processes, which occur at a solid-liquid interface, has long been debated8-11 because of the challenges of observing such interfaces directly. Here we adapt a technique that has enabled cryo-transmission electron microscopy (cryo-TEM) of hydrated specimens in biology-immobilization of liquids by rapid freezing, that is, vitrification12. By vitrifying the liquid electrolyte we preserve it and the structures at solid-liquid interfaces in lithium-metal batteries in their native state, and thus enable structural and chemical mapping of these interfaces by cryo-scanning transmission electron microscopy (cryo-STEM). We identify two dendrite types coexisting on the lithium anode, each with distinct structure and composition. One family of dendrites has an extended solid-electrolyte interphase layer, whereas the other unexpectedly consists of lithium hydride instead of lithium metal and may contribute disproportionately to loss of battery capacity. The insights into the formation of lithium dendrites that our work provides demonstrate the potential of cryogenic electron microscopy for probing nanoscale processes at intact solid-liquid interfaces in functional devices such as rechargeable batteries.}, } @article {pmid30111788, year = {2018}, author = {Frölicher, TL and Fischer, EM and Gruber, N}, title = {Marine heatwaves under global warming.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {360-364}, doi = {10.1038/s41586-018-0383-9}, pmid = {30111788}, issn = {1476-4687}, abstract = {Marine heatwaves (MHWs) are periods of extreme warm sea surface temperature that persist for days to months1 and can extend up to thousands of kilometres2. Some of the recently observed marine heatwaves revealed the high vulnerability of marine ecosystems3-11 and fisheries12-14 to such extreme climate events. Yet our knowledge about past occurrences15 and the future progression of MHWs is very limited. Here we use satellite observations and a suite of Earth system model simulations to show that MHWs have already become longer-lasting and more frequent, extensive and intense in the past few decades, and that this trend will accelerate under further global warming. Between 1982 and 2016, we detect a doubling in the number of MHW days, and this number is projected to further increase on average by a factor of 16 for global warming of 1.5 degrees Celsius relative to preindustrial levels and by a factor of 23 for global warming of 2.0 degrees Celsius. However, current national policies for the reduction of global carbon emissions are predicted to result in global warming of about 3.5 degrees Celsius by the end of the twenty-first century16, for which models project an average increase in the probability of MHWs by a factor of 41. At this level of warming, MHWs have an average spatial extent that is 21 times bigger than in preindustrial times, last on average 112 days and reach maximum sea surface temperature anomaly intensities of 2.5 degrees Celsius. The largest changes are projected to occur in the western tropical Pacific and Arctic oceans. Today, 87 per cent of MHWs are attributable to human-induced warming, with this ratio increasing to nearly 100 per cent under any global warming scenario exceeding 2 degrees Celsius. Our results suggest that MHWs will become very frequent and extreme under global warming, probably pushing marine organisms and ecosystems to the limits of their resilience and even beyond, which could cause irreversible changes.}, } @article {pmid30111544, year = {2018}, author = {Rizzo, AA and Vassel, FM and Chatterjee, N and D'Souza, S and Li, Y and Hao, B and Hemann, MT and Walker, GC and Korzhnev, DM}, title = {Rev7 dimerization is important for assembly and function of the Rev1/Polζ translesion synthesis complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8191-E8200}, pmid = {30111544}, issn = {1091-6490}, support = {R01 ES015818/ES/NIEHS NIH HHS/United States ; P41 GM103485/GM/NIGMS NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; R01 GM099948/GM/NIGMS NIH HHS/United States ; R01 GM123239/GM/NIGMS NIH HHS/United States ; R56 ES015818/ES/NIEHS NIH HHS/United States ; R35 ES028303/ES/NIEHS NIH HHS/United States ; }, mesh = {Cell Line ; DNA Damage ; DNA-Directed DNA Polymerase/chemistry/genetics/metabolism ; Humans ; *Mad2 Proteins/chemistry/genetics/metabolism ; *Nuclear Proteins/chemistry/genetics/metabolism ; *Nucleotidyltransferases/chemistry/genetics/metabolism ; Protein Domains ; *Protein Multimerization ; }, abstract = {The translesion synthesis (TLS) polymerases Polζ and Rev1 form a complex that enables replication of damaged DNA. The Rev7 subunit of Polζ, which is a multifaceted HORMA (Hop1, Rev7, Mad2) protein with roles in TLS, DNA repair, and cell-cycle control, facilitates assembly of this complex by binding Rev1 and the catalytic subunit of Polζ, Rev3. Rev7 interacts with Rev3 by a mechanism conserved among HORMA proteins, whereby an open-to-closed transition locks the ligand underneath the "safety belt" loop. Dimerization of HORMA proteins promotes binding and release of this ligand, as exemplified by the Rev7 homolog, Mad2. Here, we investigate the dimerization of Rev7 when bound to the two Rev7-binding motifs (RBMs) in Rev3 by combining in vitro analyses of Rev7 structure and interactions with a functional assay in a Rev7-/- cell line. We demonstrate that Rev7 uses the conventional HORMA dimerization interface both to form a homodimer when tethered by the two RBMs in Rev3 and to heterodimerize with other HORMA domains, Mad2 and p31comet Structurally, the Rev7 dimer can bind only one copy of Rev1, revealing an unexpected Rev1/Polζ architecture. In cells, mutation of the Rev7 dimer interface increases sensitivity to DNA damage. These results provide insights into the structure of the Rev1/Polζ TLS assembly and highlight the function of Rev7 homo- and heterodimerization.}, } @article {pmid30111543, year = {2018}, author = {Wu, D and Struwe, WB and Harvey, DJ and Ferguson, MAJ and Robinson, CV}, title = {N-glycan microheterogeneity regulates interactions of plasma proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8763-8768}, pmid = {30111543}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 641317//European Research Council/International ; MR/N020413/1//Medical Research Council/United Kingdom ; 104633/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Glucans/*chemistry/metabolism ; Haptoglobins/*chemistry/metabolism ; Humans ; *Models, Chemical ; Orosomucoid/*chemistry/metabolism ; Warfarin/*chemistry ; }, abstract = {Altered glycosylation patterns of plasma proteins are associated with autoimmune disorders and pathogenesis of various cancers. Elucidating glycoprotein microheterogeneity and relating subtle changes in the glycan structural repertoire to changes in protein-protein, or protein-small molecule interactions, remains a significant challenge in glycobiology. Here, we apply mass spectrometry-based approaches to elucidate the global and site-specific microheterogeneity of two plasma proteins: α1-acid glycoprotein (AGP) and haptoglobin (Hp). We then determine the dissociation constants of the anticoagulant warfarin to different AGP glycoforms and reveal how subtle N-glycan differences, namely, increased antennae branching and terminal fucosylation, reduce drug-binding affinity. Conversely, similar analysis of the haptoglobin-hemoglobin (Hp-Hb) complex reveals the contrary effects of fucosylation and N-glycan branching on Hp-Hb interactions. Taken together, our results not only elucidate how glycoprotein microheterogeneity regulates protein-drug/protein interactions but also inform the pharmacokinetics of plasma proteins, many of which are drug targets, and whose glycosylation status changes in various disease states.}, } @article {pmid30111542, year = {2018}, author = {Anderies, JM and Mathias, JD and Janssen, MA}, title = {Knowledge infrastructure and safe operating spaces in social-ecological systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802885115}, pmid = {30111542}, issn = {1091-6490}, abstract = {Maintaining safe operating spaces for exploited natural systems in the face of uncertainty is a key sustainability challenge. This challenge can be viewed as a problem in which human society must navigate in a limited space of acceptable futures in which humans enjoy sufficient well-being and avoid crossing planetary boundaries. A critical obstacle is the nature of society as a controller with endogenous dynamics affected by knowledge, values, and decision-making fallacies. We outline an approach for analyzing the role of knowledge infrastructure in maintaining safe operating spaces. Using a classic natural resource problem as an illustration, we find that a small safe operating space exists that is insensitive to the type of policy implementation, while in general, a larger safe operating space exists which is dependent on the implementation of the "right" policy. Our analysis suggests the importance of considering societal response dynamics to varying policy instruments in defining the shape of safe operating spaces.}, } @article {pmid30111541, year = {2018}, author = {Kalinin, N and Guzmán-Sáenz, A and Prieto, Y and Shkolnikov, M and Kalinina, V and Lupercio, E}, title = {Self-organized criticality and pattern emergence through the lens of tropical geometry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8135-E8142}, pmid = {30111541}, issn = {1091-6490}, abstract = {Tropical geometry, an established field in pure mathematics, is a place where string theory, mirror symmetry, computational algebra, auction theory, and so forth meet and influence one another. In this paper, we report on our discovery of a tropical model with self-organized criticality (SOC) behavior. Our model is continuous, in contrast to all known models of SOC, and is a certain scaling limit of the sandpile model, the first and archetypical model of SOC. We describe how our model is related to pattern formation and proportional growth phenomena and discuss the dichotomy between continuous and discrete models in several contexts. Our aim in this context is to present an idealized tropical toy model (cf. Turing reaction-diffusion model), requiring further investigation.}, } @article {pmid30111540, year = {2018}, author = {Guan, X and Chen, C}, title = {General methodology for inferring failure-spreading dynamics in networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8125-E8134}, pmid = {30111540}, issn = {1091-6490}, support = {R01 GM108731/GM/NIGMS NIH HHS/United States ; }, mesh = {*Models, Theoretical ; }, abstract = {A generic modeling framework to infer the failure-spreading process based on failure times of individual nodes is proposed and tested in four simulation studies: one for cascading failures in interdependent power and transportation networks, one for influenza epidemics, one benchmark test case for congestion cascade in a transportation network, and one benchmark test case for cascading power outages. Four general failure-spreading mechanisms-external, temporal, spatial, and functional-are quantified to capture what drives the spreading of failures. With the failure time of each node given, the proposed methodology demonstrates remarkable capability of inferring the underlying general failure-spreading mechanisms and accurately reconstructing the failure-spreading process in all four simulation studies. The analysis of the two benchmark test cases also reveals the robustness of the proposed methodology: It is shown that a failure-spreading process embedded by specific failure-spreading mechanisms such as flow redistribution can be captured with low uncertainty by our model. The proposed methodology thereby presents a promising channel for providing a generally applicable framework for modeling, understanding, and controlling failure spreading in a variety of systems.}, } @article {pmid30111539, year = {2018}, author = {Moser, J and Miller, I and Carter, D and Spencer, SL}, title = {Control of the Restriction Point by Rb and p21.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8219-E8227}, pmid = {30111539}, issn = {1091-6490}, support = {K22 CA188144/CA/NCI NIH HHS/United States ; S10 OD021601/OD/NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Cycle/*physiology ; Cell Line, Tumor ; Cyclin-Dependent Kinase 2/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p21/genetics/*metabolism ; Humans ; *Models, Biological ; *Proteolysis ; Retinoblastoma Protein/genetics/*metabolism ; }, abstract = {The Restriction Point was originally defined as the moment that cells commit to the cell cycle and was later suggested to coincide with hyperphosphorylation of the retinoblastoma protein (Rb). Current cell cycle models posit that cells exit mitosis into a pre-Restriction Point state, where they have low cyclin-dependent kinase (CDK) activity and hypophosphorylated Rb; passage through the Restriction Point then occurs in late G1. Recent single-cell studies have challenged the current paradigm, raising questions about the location of the Restriction Point and the notion that cells exit mitosis into a pre-Restriction Point state. Here, we use a variety of single-cell techniques to show that both noncancer and cancer cells bifurcate into two subpopulations after anaphase, marked by increasing vs. low CDK2 activity and hyper- vs. hypophosphorylation of Rb. Notably, subpopulations with hyper- and hypophosphorylated Rb are present within minutes after anaphase, delineating one subpopulation that never "uncrosses" the Restriction Point and continues cycling and another subpopulation that exits mitosis into an uncommitted pre-Restriction Point state. We further show that the CDK inhibitor p21 begins rising in G2 in mother cells whose daughters exit mitosis into the pre-Restriction Point, CDK2low state. Furthermore, degradation of p21 coincides with escape from the CDK2low state and passage through the Restriction Point. Together, these data support a model in which only a subset of cells returns to a pre-Restriction Point state after mitosis and where the Restriction Point is sensitive to not only mitogens, but also inherited DNA replication stress via p21.}, } @article {pmid30111538, year = {2018}, author = {Ori, H and Marder, E and Marom, S}, title = {Cellular function given parametric variation in the Hodgkin and Huxley model of excitability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8211-E8218}, pmid = {30111538}, issn = {1091-6490}, support = {R35 NS097343/NS/NINDS NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; Animals ; Axons/*physiology ; Decapodiformes ; *Models, Neurological ; }, abstract = {How is reliable physiological function maintained in cells despite considerable variability in the values of key parameters of multiple interacting processes that govern that function? Here, we use the classic Hodgkin-Huxley formulation of the squid giant axon action potential to propose a possible approach to this problem. Although the full Hodgkin-Huxley model is very sensitive to fluctuations that independently occur in its many parameters, the outcome is in fact determined by simple combinations of these parameters along two physiological dimensions: structural and kinetic (denoted S and K, respectively). Structural parameters describe the properties of the cell, including its capacitance and the densities of its ion channels. Kinetic parameters are those that describe the opening and closing of the voltage-dependent conductances. The impacts of parametric fluctuations on the dynamics of the system-seemingly complex in the high-dimensional representation of the Hodgkin-Huxley model-are tractable when examined within the S-K plane. We demonstrate that slow inactivation, a ubiquitous activity-dependent feature of ionic channels, is a powerful local homeostatic control mechanism that stabilizes excitability amid changes in structural and kinetic parameters.}, } @article {pmid30111360, year = {2018}, author = {Vaquera, E and Jones, R and Marí-Klose, P and Marí-Klose, M and Cunningham, SA}, title = {Unhealthy weight among children in Spain and the role of the home environment.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {591}, pmid = {30111360}, issn = {1756-0500}, mesh = {*Body Mass Index ; Body Weight ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Humans ; Male ; Obesity ; Overweight ; Pediatric Obesity/*epidemiology ; Prevalence ; Spain/epidemiology ; *Thinness ; }, abstract = {OBJECTIVE: Unhealthy weight is a major global health concern. This study examines unhealthy weight among children in Spain and the role of the home environment therein. Data are from a 2010 national survey of families with children. We examined unhealthy weight among children ages 5-10 years using the WHO Child Growth Standards and used multivariate logistic regression to assess associations with family characteristics.

RESULTS: There was a high prevalence of unhealthy weight, with only 46% of children at normal weight. Both underweight and obesity were higher among boys (14%; 22%) than girls (13%; 12%). Underweight and obesity were higher among children of mothers with obesity and those with unemployed parents. Obesity was higher among children of mothers who were less educated (35%) and among children of immigrants (19%). We find high levels of unhealthy weight in children, with both underweight and obesity being predicted by the same family environment characteristics.}, } @article {pmid30111292, year = {2018}, author = {Eimanifar, A and Brooks, SA and Bustamante, T and Ellis, JD}, title = {Population genomics and morphometric assignment of western honey bees (Apis mellifera L.) in the Republic of South Africa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {615}, pmid = {30111292}, issn = {1471-2164}, support = {USDA-APHIS, Projects 14-8130-0414-CA and 16-8130-0414-CA//United States Department of Agriculture, Animal and Plant Health Inspection Service/ ; }, mesh = {Animals ; Bayes Theorem ; Bees/anatomy & histology/*classification/*genetics ; Genetic Markers ; Genotype ; Geography ; Metagenomics ; Polymorphism, Single Nucleotide ; South Africa ; }, abstract = {BACKGROUNDS: Apis mellifera scutellata and A.m. capensis (the Cape honey bee) are western honey bee subspecies indigenous to the Republic of South Africa (RSA). Both bees are important for biological and economic reasons. First, A.m. scutellata is the invasive "African honey bee" of the Americas and exhibits a number of traits that beekeepers consider undesirable. They swarm excessively, are prone to absconding (vacating the nest entirely), usurp other honey bee colonies, and exhibit heightened defensiveness. Second, Cape honey bees are socially parasitic bees; the workers can reproduce thelytokously. Both bees are indistinguishable visually. Therefore, we employed Genotyping-by-Sequencing (GBS), wing geometry and standard morphometric approaches to assess the genetic diversity and population structure of these bees to search for diagnostic markers that can be employed to distinguish between the two subspecies.

RESULTS: Apis mellifera scutellata possessed the highest mean number of polymorphic SNPs (among 2449 informative SNPs) with minor allele frequencies > 0.05 (Np = 88%). The RSA honey bees generated a high level of expected heterozygosity (Hexp = 0.24). The mean genetic differentiation (FST; 6.5%) among the RSA honey bees revealed that approximately 93% of the genetic variation was accounted for within individuals of these subspecies. Two genetically distinct clusters (K = 2) corresponding to both subspecies were detected by Model-based Bayesian clustering and supported by Principal Coordinates Analysis (PCoA) inferences. Selected highly divergent loci (n = 83) further reinforced a distinctive clustering of two subspecies across geographical origins, accounting for approximately 83% of the total variation in the PCoA plot. The significant correlation of allele frequencies at divergent loci with environmental variables suggested that these populations are adapted to local conditions. Only 17 of 48 wing geometry and standard morphometric parameters were useful for clustering A.m. capensis, A.m. scutellata, and hybrid individuals.

CONCLUSIONS: We produced a minimal set of 83 SNP loci and 17 wing geometry and standard morphometric parameters useful for identifying the two RSA honey bee subspecies by genotype and phenotype. We found that genes involved in neurology/behavior and development/growth are the most prominent heritable traits evolved in the functional evolution of honey bee populations in RSA. These findings provide a starting point for understanding the functional basis of morphological differentiations and ecological adaptations of the two honey bee subspecies in RSA.}, } @article {pmid30111287, year = {2018}, author = {Ju, C and Zhang, W and Liu, Y and Gao, Y and Wang, X and Yan, J and Yang, X and Li, J}, title = {Genetic analysis of seedling root traits reveals the association of root trait with other agronomic traits in maize.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {171}, pmid = {30111287}, issn = {1471-2229}, support = {31770296//National Natural Science Foundation of China/ ; 6172002//Natural Science Foundation of Beijing Municipality/ ; }, mesh = {Edible Grain/genetics/metabolism ; Phenotype ; *Plant Breeding ; Plant Roots/genetics/metabolism ; *Quantitative Trait Loci ; Seedlings/genetics/metabolism ; Zea mays/*genetics/metabolism ; }, abstract = {BACKGROUND: Root systems play important roles in crop growth and stress responses. Although genetic mechanism of root traits in maize (Zea mays L.) has been investigated in different mapping populations, root traits have rarely been utilized in breeding programs. Elucidation of the genetic basis of maize root traits and, more importantly, their connection to other agronomic trait(s), such as grain yield, may facilitate root trait manipulation and maize germplasm improvement. In this study, we analyzed genome-wide genetic loci for maize seedling root traits at three time-points after seed germination to identify chromosomal regions responsible for both seedling root traits and other agronomic traits in a recombinant inbred line (RIL) population (Zong3 × Yu87-1).

RESULTS: Eight seedling root traits were examined at 4, 9, and 14 days after seed germination, and thirty-six putative quantitative trait loci (QTLs), accounting for 9.0-23.2% of the phenotypic variation in root traits, were detected. Co-localization of root trait QTLs was observed at, but not between, the three time-points. We identified strong or moderate correlations between root traits controlled by each co-localized QTL region. Furthermore, we identified an overlap in the QTL locations of seedling root traits examined here and six other traits reported previously in the same RIL population, including grain yield-related traits, plant height-related traits, and traits in relation to stress responses. Maize chromosomal bins 1.02-1.03, 1.07, 2.06-2.07, 5.05, 7.02-7.03, 9.04, and 10.06 were identified QTL hotspots for three or four more traits in addition to seedling root traits.

CONCLUSIONS: Our identification of co-localization of root trait QTLs at, but not between, each of the three time-points suggests that maize seedling root traits are regulated by different sets of pleiotropic-effect QTLs at different developmental stages. Furthermore, the identification of QTL hotspots suggests the genetic association of seedling root traits with several other traits and reveals maize chromosomal regions valuable for marker-assisted selection to improve root systems and other agronomic traits simultaneously.}, } @article {pmid30111285, year = {2018}, author = {Jiménez-Galindo, JC and Malvar, RA and Butrón, A and Caicedo, M and Ordás, B}, title = {Fine analysis of a genomic region involved in resistance to Mediterranean corn borer.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {169}, pmid = {30111285}, issn = {1471-2229}, mesh = {Animals ; *Antibiosis ; Chromosome Mapping ; Flowers/growth & development ; *Genome, Plant ; *Herbivory ; Larva/growth & development/*physiology ; Moths/growth & development/*physiology ; Plant Stems ; *Quantitative Trait Loci ; Seeds ; Zea mays/*genetics ; }, abstract = {BACKGROUND: Sesamia nonagrioides Lefebvere (Mediterranean corn borer, MCB) is the main pest of maize in the Mediterranean area. QTL for MCB stalk tunneling and grain yield under high MCB infestation had been located at bin 8.03-8.05 (4-21 cM and 10-30 cM respectively) in a previous analysis of the EP42 x EP39 RILs mapping population. The objective of the present work was to study with higher resolution those QTL, and validating and estimating with higher precision their locations and effects. To achieve this objective, we developed a set of 38 heterogeneous inbred families (HIFs) which were near-homozygous in the genome, except in the region under study. The HIFs were evaluated in multiple environments under artificial infestation with MCB and genotyped with SNPs.

RESULTS: The QTL for grain yield under high infestation was confirmed with higher precision and improved reliability at 112.6-116.9 Mb. On the contrary, the location of the QTL for stalk tunneling was not validated probably due to the fixation of some genomic regions during the development of the HIFs. Our study confirmed that the co-localization of the QTL for stalk tunneling and grain yield in the previous study was due to linked genes, not to pleiotropic effects. So, the QTL for grain yield can be used for improving grain yield without undesirable effect on stalk tunneling.

CONCLUSIONS: The HIF analysis is useful for validating QTL and for conducting deeper studies in traits related to corn borer resistance.}, } @article {pmid30111282, year = {2018}, author = {Tai, Y and Liu, C and Yu, S and Yang, H and Sun, J and Guo, C and Huang, B and Liu, Z and Yuan, Y and Xia, E and Wei, C and Wan, X}, title = {Gene co-expression network analysis reveals coordinated regulation of three characteristic secondary biosynthetic pathways in tea plant (Camellia sinensis).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {616}, pmid = {30111282}, issn = {1471-2164}, support = {13Z03012//Science and Technology Project of AnHui Province, China/ ; No. 31170283//Natural Science Foundation of Anhui Province/ ; 2016ZR012//the Youth Foundation of Anhui Agricultural University/ ; }, mesh = {Caffeine/metabolism ; Camellia sinensis/chemistry/*genetics/*metabolism ; Catechin/metabolism ; Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Glutamates/metabolism ; High-Throughput Nucleotide Sequencing/methods ; Metabolic Networks and Pathways ; Plant Leaves/genetics/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: The leaves of tea plants (Camellia sinensis) are used to produce tea, which is one of the most popular beverages consumed worldwide. The nutritional value and health benefits of tea are mainly related to three abundant characteristic metabolites; catechins, theanine and caffeine. Weighted gene co-expression network analysis (WGCNA) is a powerful system for investigating correlations between genes, identifying modules among highly correlated genes, and relating modules to phenotypic traits based on gene expression profiling. Currently, relatively little is known about the regulatory mechanisms and correlations between these three secondary metabolic pathways at the omics level in tea.

RESULTS: In this study, levels of the three secondary metabolites in ten different tissues of tea plants were determined, 87,319 high-quality unigenes were assembled, and 55,607 differentially expressed genes (DEGs) were identified by pairwise comparison. The resultant co-expression network included 35 co-expression modules, of which 20 modules were significantly associated with the biosynthesis of catechins, theanine and caffeine. Furthermore, we identified several hub genes related to these three metabolic pathways, and analysed their regulatory relationships using RNA-Seq data. The results showed that these hub genes are regulated by genes involved in all three metabolic pathways, and they regulate the biosynthesis of all three metabolites. It is notable that light was identified as an important regulator for the biosynthesis of catechins.

CONCLUSION: Our integrated omics-level WGCNA analysis provides novel insights into the potential regulatory mechanisms of catechins, theanine and caffeine metabolism, and the identified hub genes provide an important reference for further research on the molecular biology of tea plants.}, } @article {pmid30111279, year = {2018}, author = {Hackett, CA and Milne, L and Smith, K and Hedley, P and Morris, J and Simpson, CG and Preedy, K and Graham, J}, title = {Enhancement of Glen Moy x Latham raspberry linkage map using GbS to further understand control of developmental processes leading to fruit ripening.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {59}, pmid = {30111279}, issn = {1471-2156}, abstract = {BACKGROUND: The changing climate is altering timing of key fruit ripening processes and increasing the occurrence of fruit defects. To improve our understanding of the genetic control of raspberry fruit development an enhanced genetic linkage map was developed and used to examine ripening phenotypic data.

RESULTS: In this study we developed an enhanced genetic linkage map for the raspberry cvs. Glen Moy x Latham reference mapping population using genotyping by sequencing (GbS). Alignment to a newly sequenced draft reference genome of red raspberry, cultivar (cv.) Glen Moy, identified 8019 single nucleotide polymorphisms (SNPs). After stringent filtering to take account of read coverage over all the progeny individuals, association with a single chromosome, heterozygosity and marker regression mapping, 2348 high confidence SNPs were retained and integrated with an existing raspberry genetic map. The linkage map contained many more SNPs segregating in Latham than in Glen Moy. This caused difficulties in quantitative trait loci (QTL) mapping with standard software and a novel analysis based on a hidden Markov model was used to improve the mapping. QTL mapping using the newly generated dense genetic map not only corroborated previously identified genetic locations but also provided additional genetic elements controlling fruit ripening in raspberry.

CONCLUSION: The high-density GbS map located the QTL peaks more precisely than in earlier studies, aligned the QTLs with Glen Moy genome scaffolds, narrowed the range of potential candidate genes to these regions that can be utilised in other populations or in gene expression studies to confirm their role and increased the repertoire of markers available to understand the genetic control of fruit ripening traits.}, } @article {pmid30111278, year = {2018}, author = {Arias, RS and Sobolev, VS and Massa, AN and Orner, VA and Walk, TE and Ballard, LL and Simpson, SA and Puppala, N and Scheffler, BE and de Blas, F and Seijo, GJ}, title = {New tools to screen wild peanut species for aflatoxin accumulation and genetic fingerprinting.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {170}, pmid = {30111278}, issn = {1471-2229}, support = {NP301 6604-21000-004-00D//USDA-ARS/ ; NP303 6604-42000-008-00D//USDA-ARS/ ; }, mesh = {Aflatoxins/*metabolism ; Arachis/*genetics ; Aspergillus flavus/chemistry ; DNA Fingerprinting/economics/*methods ; *Genetic Markers ; *Microsatellite Repeats ; Reproducibility of Results ; Seed Bank ; Seeds/metabolism/microbiology ; }, abstract = {BACKGROUND: Aflatoxin contamination in peanut seeds is still a serious problem for the industry and human health. No stable aflatoxin resistant cultivars have yet been produced, and given the narrow genetic background of cultivated peanuts, wild species became an important source of genetic diversity. Wild peanut seeds, however, are not abundant, thus, an effective method of screening for aflatoxin accumulation using minimal seeds is highly desirable. In addition, keeping record of genetic fingerprinting of each accession would be very useful for breeding programs and for the identification of accessions within germplasm collections.

RESULTS: In this study, we report a method of screening for aflatoxin accumulation that is applicable to the small-size seeds of wild peanuts, increases the reliability by testing seed viability, and records the genetic fingerprinting of the samples. Aflatoxin levels observed among 20 wild peanut species varied from zero to 19000 ng.g-1 and 155 ng.g-1 of aflatoxin B1 and B2, respectively. We report the screening of 373 molecular markers, including 288 novel SSRs, tested on 20 wild peanut species. Multivariate analysis by Neighbor-Joining, Principal Component Analysis and 3D-Principal Coordinate Analysis using 134 (36 %) transferable markers, in general grouped the samples according to their reported genomes. The best 88 markers, those with high fluorescence, good scorability and transferability, are reported with BLAST results. High quality markers (total 98) that discriminated genomes are reported. A high quality marker with UPIC score 16 (16 out of 20 species discriminated) had significant hits on BLAST2GO to a pentatricopeptide-repeat protein, another marker with score 5 had hits on UDP-D-apiose synthase, and a third one with score 12 had BLASTn hits on La-RP 1B protein. Together, these three markers discriminated all 20 species tested.

CONCLUSIONS: This study provides a reliable method to screen wild species of peanut for aflatoxin resistance using minimal seeds. In addition we report 288 new SSRs for peanut, and a cost-effective combination of markers sufficient to discriminate all 20 species tested. These tools can be used for the systematic search of aflatoxin resistant germplasm keeping record of the genetic fingerprinting of the accessions tested for breeding purpose.}, } @article {pmid30111276, year = {2018}, author = {Moorefield, EC and Blue, RE and Quinney, NL and Gentzsch, M and Ding, S}, title = {Generation of renewable mouse intestinal epithelial cell monolayers and organoids for functional analyses.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {15}, pmid = {30111276}, issn = {1471-2121}, support = {P30 DK065988/DK/NIDDK NIH HHS/United States ; P30 DK065988/NH/NIH HHS/United States ; }, mesh = {3T3 Cells ; Adenomatous Polyposis Coli/metabolism/pathology ; Alleles ; Animals ; Cell Proliferation ; Cell Self Renewal ; Cell Shape ; Cells, Cultured ; Cellular Reprogramming ; Cystic Fibrosis/metabolism/pathology ; Cystic Fibrosis Transmembrane Conductance Regulator/metabolism ; Epithelial Cells/*cytology/metabolism ; Intestinal Mucosa/cytology ; Intestines/*cytology ; Mice ; Mice, Inbred C57BL ; Mutation/genetics ; Organoids/*cytology ; }, abstract = {BACKGROUND: Conditional reprogramming has enabled the development of long-lived, normal epithelial cell lines from mice and humans by in vitro culture with ROCK inhibitor on a feeder layer. We applied this technology to mouse small intestine to create 2D mouse intestinal epithelial monolayers (IEC monolayers) from genetic mouse models for functional analysis.

RESULTS: IEC monolayers form epithelial colonies that proliferate on a feeder cell layer and are able to maintain their genotype over long-term passage. IEC monolayers form 3D spheroids in matrigel culture and monolayers on transwell inserts making them useful for functional analyses. IEC monolayers derived from the Cystic Fibrosis (CF) mouse model CFTR ∆F508 fail to respond to CFTR activator forskolin in 3D matrigel culture as measured by spheroid swelling and transwell monolayer culture via Ussing chamber electrophysiology. Tumor IEC monolayers generated from the ApcMin/+ mouse intestinal cancer model grow more quickly than wild-type (WT) IEC monolayers both on feeders and as spheroids in matrigel culture.

CONCLUSIONS: These results indicate that generation of IEC monolayers is a useful model system for growing large numbers of genotype-specific mouse intestinal epithelial cells that may be used in functional studies to examine molecular mechanisms of disease and to identify and assess novel therapeutic compounds.}, } @article {pmid30110663, year = {2018}, author = {Gillung, JP and Winterton, SL and Bayless, KM and Khouri, Z and Borowiec, ML and Yeates, D and Kimsey, LS and Misof, B and Shin, S and Zhou, X and Mayer, C and Petersen, M and Wiegmann, BM}, title = {Anchored phylogenomics unravels the evolution of spider flies (Diptera, Acroceridae) and reveals discordance between nucleotides and amino acids.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {233-245}, doi = {10.1016/j.ympev.2018.08.007}, pmid = {30110663}, issn = {1095-9513}, abstract = {The onset of phylogenomics has contributed to the resolution of numerous challenging evolutionary questions while offering new perspectives regarding biodiversity. However, in some instances, analyses of large genomic datasets can also result in conflicting estimates of phylogeny. Here, we present the first phylogenomic scale study of a dipteran parasitoid family, built upon anchored hybrid enrichment and transcriptomic data of 240 loci of 43 ingroup acrocerid taxa. A new hypothesis for the timing of spider fly evolution is proposed, wielding recent advances in divergence time dating, including the fossilized birth-death process to show that the origin of Acroceridae is younger than previously proposed. To test the robustness of our phylogenetic inferences, we analyzed our datasets using different phylogenetic estimation criteria, including supermatrix and coalescent-based approaches, maximum-likelihood and Bayesian methods, combined with other approaches such as permutations of the data, homogeneous versus heterogeneous models, and alternative data and taxon sets. Resulting topologies based on amino acids and nucleotides are both strongly supported but critically discordant, primarily in terms of the monophyly of Panopinae. Conflict was not resolved by controlling for compositional heterogeneity and saturation in third codon positions, which highlights the need for a better understanding of how different biases affect different data sources. In our study, results based on nucleotides were both more robust to alterations of the data and different analytical methods and more compatible with our current understanding of acrocerid morphology and patterns of host usage.}, } @article {pmid30110558, year = {2018}, author = {Schoenherr, C and Frame, MC and Byron, A}, title = {Trafficking of Adhesion and Growth Factor Receptors and Their Effector Kinases.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {29-58}, doi = {10.1146/annurev-cellbio-100617-062559}, pmid = {30110558}, issn = {1530-8995}, abstract = {Cell adhesion to macromolecules in the microenvironment is essential for the development and maintenance of tissues, and its dysregulation can lead to a range of disease states, including inflammation, fibrosis, and cancer. The biomechanical and biochemical mechanisms that mediate cell adhesion rely on signaling by a range of effector proteins, including kinases and associated scaffolding proteins. The intracellular trafficking of these must be tightly controlled in space and time to enable effective cell adhesion and microenvironmental sensing and to integrate cell adhesion with, and compartmentalize it from, other cellular processes, such as gene transcription, protein degradation, and cell division. Delivery of adhesion receptors and signaling proteins from the plasma membrane to unanticipated subcellular locales is revealing novel biological functions. Here, we review the expected and unexpected trafficking, and sites of activity, of adhesion and growth factor receptors and intracellular kinase partners as we begin to appreciate the complexity and diversity of their spatial regulation.}, } @article {pmid30110557, year = {2018}, author = {Pishesha, N and Ingram, JR and Ploegh, HL}, title = {Sortase A: A Model for Transpeptidation and Its Biological Applications.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {163-188}, doi = {10.1146/annurev-cellbio-100617-062527}, pmid = {30110557}, issn = {1530-8995}, abstract = {Molecular biologists and chemists alike have long sought to modify proteins with substituents that cannot be installed by standard or even advanced genetic approaches. We here describe the use of transpeptidases to achieve these goals. Living systems encode a variety of transpeptidases and peptide ligases that allow for the enzyme-catalyzed formation of peptide bonds, and protein engineers have used directed evolution to enhance these enzymes for biological applications. We focus primarily on the transpeptidase sortase A, which has become popular over the past few years for its ability to perform a remarkably wide variety of protein modifications, both in vitro and in living cells.}, } @article {pmid30110556, year = {2018}, author = {Oh, E and Akopian, D and Rape, M}, title = {Principles of Ubiquitin-Dependent Signaling.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {137-162}, doi = {10.1146/annurev-cellbio-100617-062802}, pmid = {30110556}, issn = {1530-8995}, abstract = {Ubiquitylation is an essential posttranslational modification that controls cell division, differentiation, and survival in all eukaryotes. By combining multiple E3 ligases (writers), ubiquitin-binding effectors (readers), and de-ubiquitylases (erasers) with functionally distinct ubiquitylation tags, the ubiquitin system constitutes a powerful signaling network that is employed in similar ways from yeast to humans. Here, we discuss conserved principles of ubiquitin-dependent signaling that illustrate how this posttranslational modification shapes intracellular signaling networks to establish robust development and homeostasis throughout the eukaryotic kingdom.}, } @article {pmid30109768, year = {2018}, author = {Moll, J and Kellner, H and Leonhardt, S and Stengel, E and Dahl, A and Bässler, C and Buscot, F and Hofrichter, M and Hoppe, B}, title = {Bacteria inhabiting deadwood of 13 tree species are heterogeneously distributed between sapwood and heartwood.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3744-3756}, doi = {10.1111/1462-2920.14376}, pmid = {30109768}, issn = {1462-2920}, support = {BA5127/1-1//DFG Priority Program 1374/ ; BU 941/17-1//DFG Priority Program 1374/ ; HO 1961/6-1//DFG Priority Program 1374/ ; KE 1742/2-1//DFG Priority Program 1374/ ; }, abstract = {Deadwood represents an important structural component of forest ecosystems, where it provides diverse niches for saproxylic biota. Although wood-inhabiting prokaryotes are involved in its degradation, knowledge about their diversity and the drivers of community structure is scarce. To explore the effect of deadwood substrate on microbial distribution, the present study focuses on the microbial communities of deadwood logs from 13 different tree species investigated using an amplicon based deep-sequencing analysis. Sapwood and heartwood communities were analysed separately and linked to various relevant wood physico-chemical parameters. Overall, Proteobacteria, Acidobacteria and Actinobacteria represented the most dominant phyla. Microbial OTU richness and community structure differed significantly between tree species and between sapwood and heartwood. These differences were more pronounced for heartwood than for sapwood. The pH value and water content were the most important drivers in both wood compartments. Overall, investigating numerous tree species and two compartments provided a remarkably comprehensive view of microbial diversity in deadwood.}, } @article {pmid30109758, year = {2018}, author = {Bertin, Y and Segura, A and Jubelin, G and Dunière, L and Durand, A and Forano, E}, title = {Aspartate metabolism is involved in the maintenance of enterohaemorrhagic Escherichia coli O157:H7 in bovine intestinal content.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4473-4485}, doi = {10.1111/1462-2920.14380}, pmid = {30109758}, issn = {1462-2920}, abstract = {The gastrointestinal tract (GIT) of healthy cattle is the main reservoir of enterohaemorrhagic Escherichia coli (EHEC). Therefore, it is crucial to better understand the physiology of EHEC in the bovine GIT. In this study, we demonstrate that aspartate present in bovine small intestine content (BSIC), was exhausted after incubation of the reference EHEC strain EDL933 but was poorly assimilated by the endogenous microbiota. Furthermore, the bovine commensal E. coli strain BG1 appeared less efficient than EDL933 in aspartate assimilation suggesting a competitive ability of EHEC to assimilate this amino acid. Our results strongly suggest that aspartate, internalized via the DcuA aspartate: succinate antiporting system, is then converted to fumarate and carbamoyl-aspartate, the precursor for UMP biosynthesis. Aspartate assimilation by these two pathways conferred a competitive growth advantage to EHEC in BSIC. In summary, supply of intracellular fumarate due to aspartate deamination and used as an electron acceptor for anaerobic fumarate respiration, as well as de novo synthesis of pyrimidine from aspartate appear to be important pathways favouring EHEC persistence in the bovine gut. Aspartate probably represents an ecological niche for EHEC in the bovine small intestine.}, } @article {pmid30109757, year = {2018}, author = {Bakenhus, I and Dlugosch, L and Giebel, HA and Beardsley, C and Simon, M and Wietz, M}, title = {Distinct biogeographic patterns of bacterioplankton composition and single-cell activity between the subtropics and Antarctica.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3100-3108}, doi = {10.1111/1462-2920.14383}, pmid = {30109757}, issn = {1462-2920}, support = {TRR51WI3888/1-2//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Bacterial biogeography and activity in the Southern Ocean are poorly understood to date. Here, we applied CARD-FISH to quantify bacterial community structure from the subtropics to Antarctica between 10°W and 10°E, covering four biogeographic provinces with distinct environmental properties. In addition, incorporation of radiolabeled glucose, amino acids and leucine via MAR-FISH served to quantify the contribution to substrate turnover by selected bacterial groups. SAR11, Bacteroidetes, Gammaproteobacteria and the Roseobacter group accounted for the majority of the bacterial community (52%-88% of DAPI-stained cells) but showed little distributional variation between provinces. In contrast, taxonomic subclades Polaribacter, NS5, NS2b (Bacteroidetes) as well as RCA (Roseobacter group) featured marked geographic variation, illustrated by NMDS and coefficients of variation. Roseobacter (specifically RCA) and Gammaproteobacteria constituted considerable fractions of cells incorporating glucose and amino acids respectively. Bacteroidetes had generally lower activities, but Polaribacter accounted for a major fraction of biomass production at one station near the Antarctic ice shelf. In conclusion, distributional patterns at finer taxonomic level and highest substrate turnover by less abundant taxa highlight the importance of taxonomic subclades in marine carbon fluxes, contributing to the understanding of functional bacterial biogeography in the Southern Ocean.}, } @article {pmid30109706, year = {2018}, author = {Bonel, N and Noël, E and Janicke, T and Sartori, K and Chapuis, E and Ségard, A and Meconcelli, S and Pélissié, B and Sarda, V and David, P}, title = {Asymmetric evolutionary responses to sex-specific selection in a hermaphrodite.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2181-2201}, doi = {10.1111/evo.13565}, pmid = {30109706}, issn = {1558-5646}, support = {ANR-12-BSV7-0015//ESHAP (CNRS-ANR)/ ; }, abstract = {Sex allocation theory predicts that simultaneous hermaphrodites evolve to an evolutionary stable resource allocation, whereby any increase in investment to male reproduction leads to a disproportionate cost on female reproduction and vice versa. However, empirical evidence for sexual trade-offs in hermaphroditic animals is still limited. Here, we tested how male and female reproductive traits evolved under conditions of reduced selection on either male or female reproduction for 40 generations in a hermaphroditic snail. This selection favors a reinvestment of resources from the sex function under relaxed selection toward the other function. We found no such evolutionary response. Instead, juvenile survival and male reproductive success significantly decreased in lines where selection on the male function (i.e., sexual selection) was relaxed, while relaxing selection on the female function had no effect. Our results suggest that most polymorphisms under selection in these lines were not sex-antagonistic. Rather, they were deleterious mutations affecting juvenile survival (thus reducing both male and female fitness) with strong pleiotropic effects on male success in a sexual selection context. These mutations accumulated when sexual selection was relaxed, which supports the idea that sexual selection in hermaphrodites contributes to purge the mutation load from the genome as in separate-sex organisms.}, } @article {pmid30109428, year = {2018}, author = {Aslam, F and Yasmin, A and Thomas, T}, title = {Essential Gene Clusters Identified in Stenotrophomonas MB339 for Multiple Metal/Antibiotic Resistance and Xenobiotic Degradation.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1484-1492}, pmid = {30109428}, issn = {1432-0991}, support = {IRSIP//Higher Education Commmission, Pakistan/ ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*genetics/metabolism ; Biodegradation, Environmental ; Drug Resistance, Bacterial ; Genes, Essential ; Genome, Bacterial ; Metals, Heavy/metabolism ; Multigene Family ; Stenotrophomonas/*drug effects/genetics/isolation & purification/*metabolism ; Waste Water/*microbiology ; Xenobiotics/*metabolism ; }, abstract = {Stenotrophomonas MB339, a bacterium, which could potentially utilize aromatic compounds and tolerate different heavy metals was isolated from industrial wastewater. Subsequent experiments revealed strains ability to resist antibiotics ofloxacin, streptomycin, rifampicillin, erythromycin, ampicillin, clindamycin, and toxicants including As2+, Hg2+, Cu2+, Ni2+, Pb2+. The shotgun sequencing strategy, genome assembly and annotation uncovered specific features, which make this strain MB339 effectively promising to cope with highly contaminated conditions. This report presents isolate's assembled genome and its functional annotation identifying a set of protein coding genes (4711), tRNA (69 genes), and rRNA (9 genes). More than 2900 genes were assigned to various Clusters of Orthologous Groups (COGs) and 1114 genes attributed to 37 different Koyoto Encyclopedia of Genes and Genomes (KEGGs) pathways. Among these annotated genes, eighteen were for key enzymes taking part in xenobiotic degradation. Furthermore, 149 genes have been assigned to virulence, disease, and defense mechanisms responsible for multidrug and metal resistance including mercury, copper, and arsenic operons. These determinants comprised genes for membrane proteins, efflux pumps, and metal reductases, suggesting its potential applications in bioremediation.}, } @article {pmid30108364, year = {2018}, author = {Muhlemann, B and Jones, TC and de Barros Damgaard, P and Allentoft, ME and Shevnina, I and Logvin, A and Usmanova, E and Panyushkina, IP and Boldgiv, B and Bazartseren, T and Tashbaeva, K and Merz, V and Lau, N and Smrčka, V and Voyakin, D and Kitov, E and Epimakhov, A and Pokutta, D and Vicze, M and Price, TD and Moiseyev, V and Hansen, AJ and Orlando, L and Rasmussen, S and Sikora, M and Vinner, L and Osterhaus, ADME and Smith, DJ and Glebe, D and Fouchier, RAM and Drosten, C and Sjogren, KG and Kristiansen, K and Willerslev, E}, title = {Author Correction: Ancient hepatitis B viruses from the Bronze Age to the Medieval period.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {E4}, doi = {10.1038/s41586-018-0406-6}, pmid = {30108364}, issn = {1476-4687}, abstract = {In Fig. 2 of this Letter, the 'E' and 'G' clade labels were inadvertently reversed, and in Table 2 the genotype of DA27 was 'D1' instead of 'D5'. These have been corrected online.}, } @article {pmid30108363, year = {2018}, author = {Banerjee, M and Heiblum, M and Umansky, V and Feldman, DE and Oreg, Y and Stern, A}, title = {Author Correction: Observation of half-integer thermal Hall conductance.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {E6}, doi = {10.1038/s41586-018-0404-8}, pmid = {30108363}, issn = {1476-4687}, abstract = {In this Article, the publication details for references 33, 34 and 40 have been corrected online.}, } @article {pmid30108362, year = {2018}, author = {Nguyen, NX and Armache, JP and Lee, C and Yang, Y and Zeng, W and Mootha, VK and Cheng, Y and Bai, XC and Jiang, Y}, title = {Author Correction: Cryo-EM structure of a fungal mitochondrial calcium uniporter.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {E25}, doi = {10.1038/s41586-018-0427-1}, pmid = {30108362}, issn = {1476-4687}, abstract = {In this Article, ref. 15 has been replaced and references 32 to 50 have been renumbered online.}, } @article {pmid30108361, year = {2018}, author = {Huttenlocker, AK and Grossnickle, DM and Kirkland, JI and Schultz, JA and Luo, ZX}, title = {Publisher Correction: Late-surviving stem mammal links the lowermost Cretaceous of North America and Gondwana.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {E27}, doi = {10.1038/s41586-018-0428-0}, pmid = {30108361}, issn = {1476-4687}, abstract = {The asterisked footnote to Extended Data Table 1 should state '*Including Thomasia and Haramiyavia'. This has been corrected online.}, } @article {pmid30108360, year = {2018}, author = {Castelvecchi, D}, title = {LHC physicists embrace brute-force approach to particle hunt.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {293-294}, doi = {10.1038/d41586-018-05972-7}, pmid = {30108360}, issn = {1476-4687}, } @article {pmid30108359, year = {2018}, author = {Tollefson, J}, title = {Industry trumps peer-reviewed science at US environment agency.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {292-293}, doi = {10.1038/d41586-018-05946-9}, pmid = {30108359}, issn = {1476-4687}, } @article {pmid30108358, year = {2018}, author = {Bauld, L}, title = {Funders must be wary of industry alliances.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {283}, doi = {10.1038/d41586-018-05937-w}, pmid = {30108358}, issn = {1476-4687}, } @article {pmid30108357, year = {2018}, author = {Casado, M}, title = {Engage more early-career scientists as peer reviewers.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {307}, doi = {10.1038/d41586-018-05956-7}, pmid = {30108357}, issn = {1476-4687}, } @article {pmid30108356, year = {2018}, author = {Trant, J}, title = {Bring training forward for undergraduate researchers.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {307}, doi = {10.1038/d41586-018-05954-9}, pmid = {30108356}, issn = {1476-4687}, } @article {pmid30108355, year = {2018}, author = {King, RD and Courtney, P}, title = {Dilemma over AI and drug patenting already under debate.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {307}, doi = {10.1038/d41586-018-05955-8}, pmid = {30108355}, issn = {1476-4687}, } @article {pmid30108354, year = {2018}, author = {Pravst, I}, title = {Speed up global ban on industrial trans fats in food.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {307}, doi = {10.1038/d41586-018-05953-w}, pmid = {30108354}, issn = {1476-4687}, } @article {pmid30108353, year = {2018}, author = {Bates, AE and Helmuth, B and Burrows, MT and Duncan, MI and Garrabou, J and Guy-Haim, T and Lima, F and Queiros, AM and Seabra, R and Marsh, R and Belmaker, J and Bensoussan, N and Dong, Y and Mazaris, AD and Smale, D and Wahl, M and Rilov, G}, title = {Biologists ignore ocean weather at their peril.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {299-301}, doi = {10.1038/d41586-018-05869-5}, pmid = {30108353}, issn = {1476-4687}, } @article {pmid30108352, year = {2018}, author = {Reardon, S}, title = {How digital drug users could help to halt the US opioid epidemic.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {295-297}, doi = {10.1038/d41586-018-05939-8}, pmid = {30108352}, issn = {1476-4687}, } @article {pmid30108351, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {316}, doi = {10.1038/d41586-018-05943-y}, pmid = {30108351}, issn = {1476-4687}, } @article {pmid30108350, year = {2018}, author = {Turner, NJ}, title = {Enzymes team up with light-activated catalysts.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {310-311}, doi = {10.1038/d41586-018-05933-0}, pmid = {30108350}, issn = {1476-4687}, } @article {pmid30108348, year = {2018}, author = {Ledford, H}, title = {Gene-silencing technology gets first drug approval after 20-year wait.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {291-292}, doi = {10.1038/d41586-018-05867-7}, pmid = {30108348}, issn = {1476-4687}, } @article {pmid30108347, year = {2018}, author = {Maxmen, A}, title = {War zone complicates roll-out of Ebola vaccine in latest outbreak.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {289-290}, doi = {10.1038/d41586-018-05921-4}, pmid = {30108347}, issn = {1476-4687}, } @article {pmid30108186, year = {2018}, author = {Ornes, S}, title = {Core Concept: How does climate change influence extreme weather? Impact attribution research seeks answers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8232-8235}, pmid = {30108186}, issn = {1091-6490}, } @article {pmid30108185, year = {2018}, author = {Madhusoodanan, J}, title = {Inner Workings: Safer opioids may be on the horizon, but mitigating addiction is a long shot.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8229-8231}, pmid = {30108185}, issn = {1091-6490}, mesh = {Analgesics, Opioid/*adverse effects ; Humans ; Opioid-Related Disorders/*prevention & control ; Receptors, G-Protein-Coupled/physiology ; Receptors, Opioid, mu/physiology ; }, } @article {pmid30108150, year = {2018}, author = {Jung, MH and Sun, C and Nelson, LD}, title = {People can recognize, learn, and apply default effects in social influence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8105-E8106}, pmid = {30108150}, issn = {1091-6490}, mesh = {*Choice Behavior ; *Learning ; }, } @article {pmid30108149, year = {2018}, author = {Zlatev, JJ and Daniels, DP and Kim, H and Neale, MA}, title = {Reply to Jung et al.: Default neglect persists over time and across contexts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8107-E8108}, pmid = {30108149}, issn = {1091-6490}, } @article {pmid30108148, year = {2018}, author = {Duan, J and Li, Z and Li, J and Hulse, RE and Santa-Cruz, A and Valinsky, WC and Abiria, SA and Krapivinsky, G and Zhang, J and Clapham, DE}, title = {Structure of the mammalian TRPM7, a magnesium channel required during embryonic development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8201-E8210}, pmid = {30108148}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Embryo, Mammalian ; *Embryonic Development ; *Evolution, Molecular ; Mice ; Protein Domains ; TRPM Cation Channels/*chemistry/metabolism ; }, abstract = {The transient receptor potential ion channel subfamily M, member 7 (TRPM7), is a ubiquitously expressed protein that is required for mouse embryonic development. TRPM7 contains both an ion channel and an α-kinase. The channel domain comprises a nonselective cation channel with notable permeability to Mg2+ and Zn2+ Here, we report the closed state structures of the mouse TRPM7 channel domain in three different ionic conditions to overall resolutions of 3.3, 3.7, and 4.1 Å. The structures reveal key residues for an ion binding site in the selectivity filter, with proposed partially hydrated Mg2+ ions occupying the center of the conduction pore. In high [Mg2+], a prominent external disulfide bond is found in the pore helix, which is essential for ion channel function. Our results provide a structural framework for understanding the TRPM1/3/6/7 subfamily and extend the knowledge base upon which to study the diversity and evolution of TRP channels.}, } @article {pmid30108147, year = {2018}, author = {Raes, EJ and Bodrossy, L and van de Kamp, J and Bissett, A and Ostrowski, M and Brown, MV and Sow, SLS and Sloyan, B and Waite, AM}, title = {Oceanographic boundaries constrain microbial diversity gradients in the South Pacific Ocean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8266-E8275}, pmid = {30108147}, issn = {1091-6490}, mesh = {Antarctic Regions ; Archaea/classification/*physiology ; *Bacteria ; *Bacterial Physiological Phenomena ; *Biodiversity ; Pacific Ocean ; Phytoplankton/classification/*physiology ; *Water Microbiology ; }, abstract = {Marine microbes along with microeukaryotes are key regulators of oceanic biogeochemical pathways. Here we present a high-resolution (every 0.5° of latitude) dataset describing microbial pro- and eukaryotic richness in the surface and just below the thermocline along a 7,000-km transect from 66°S at the Antarctic ice edge to the equator in the South Pacific Ocean. The transect, conducted in austral winter, covered key oceanographic features including crossing of the polar front (PF), the subtropical front (STF), and the equatorial upwelling region. Our data indicate that temperature does not determine patterns of marine microbial richness, complementing the global model data from Ladau et al. [Ladau J, et al. (2013) ISME J 7:1669-1677]. Rather, NH4+, nanophytoplankton, and primary productivity were the main drivers for archaeal and bacterial richness. Eukaryote richness was highest in the least-productive ocean region, the tropical oligotrophic province. We also observed a unique diversity pattern in the South Pacific Ocean: a regional increase in archaeal and bacterial diversity between 10°S and the equator. Rapoport's rule describes the tendency for the latitudinal ranges of species to increase with latitude. Our data showed that the mean latitudinal ranges of archaea and bacteria decreased with latitude. We show that permanent oceanographic features, such as the STF and the equatorial upwelling, can have a significant influence on both alpha-diversity and beta-diversity of pro- and eukaryotes.}, } @article {pmid30108146, year = {2018}, author = {Braun, E and Lee, Y and Moosavi, SM and Barthel, S and Mercado, R and Baburin, IA and Proserpio, DM and Smit, B}, title = {Generating carbon schwarzites via zeolite-templating.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8116-E8124}, pmid = {30108146}, issn = {1091-6490}, abstract = {Zeolite-templated carbons (ZTCs) comprise a relatively recent material class synthesized via the chemical vapor deposition of a carbon-containing precursor on a zeolite template, followed by the removal of the template. We have developed a theoretical framework to generate a ZTC model from any given zeolite structure, which we show can successfully predict the structure of known ZTCs. We use our method to generate a library of ZTCs from all known zeolites, to establish criteria for which zeolites can produce experimentally accessible ZTCs, and to identify over 10 ZTCs that have never before been synthesized. We show that ZTCs partition space into two disjoint labyrinths that can be described by a pair of interpenetrating nets. Since such a pair of nets also describes a triply periodic minimal surface (TPMS), our results establish the relationship between ZTCs and schwarzites-carbon materials with negative Gaussian curvature that resemble TPMSs-linking the research topics and demonstrating that schwarzites should no longer be thought of as purely hypothetical materials.}, } @article {pmid30108145, year = {2018}, author = {Kumar, H and Finer-Moore, JS and Jiang, X and Smirnova, I and Kasho, V and Pardon, E and Steyaert, J and Kaback, HR and Stroud, RM}, title = {Crystal Structure of a ligand-bound LacY-Nanobody Complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8769-8774}, pmid = {30108145}, issn = {1091-6490}, support = {R01 GM024485/GM/NIGMS NIH HHS/United States ; R01 GM120043/GM/NIGMS NIH HHS/United States ; }, mesh = {Crystallography, X-Ray ; Escherichia coli/*chemistry/genetics ; Escherichia coli Proteins/*chemistry/genetics ; Monosaccharide Transport Proteins/*chemistry/genetics ; Mutation ; Protein Structure, Quaternary ; Single-Domain Antibodies/*chemistry ; Symporters/*chemistry/genetics ; }, abstract = {The lactose permease of Escherichia coli (LacY), a dynamic polytopic membrane transport protein, catalyzes galactoside/H+ symport and operates by an alternating access mechanism that exhibits multiple conformations, the distribution of which is altered by sugar-binding. Camelid nanobodies were made against a double-mutant Gly46 → Trp/Gly262 → Trp (LacYWW) that produces an outward-open conformation, as opposed to the cytoplasmic open-state crystal structure of WT LacY. Nanobody 9047 (Nb9047) stabilizes WT LacY in a periplasmic-open conformation. Here, we describe the X-ray crystal structure of a complex between LacYWW, the high-affinity substrate analog 4-nitrophenyl-α-d-galactoside (NPG), and Nb9047 at 3-Å resolution. The present crystal structure demonstrates that Nb9047 binds to the periplasmic face of LacY, primarily to the C-terminal six-helical bundle, while a flexible loop of the Nb forms a bridge between the N- and C-terminal halves of LacY across the periplasmic vestibule. The bound Nb partially covers the vestibule, yet does not affect the on-rates or off-rates for the substrate binding to LacYWW, which implicates dynamic flexibility of the Nb-LacYWW complex. Nb9047-binding neither changes the overall structure of LacYWW with bound NPG, nor the positions of side chains comprising the galactoside-binding site. The current NPG-bound structure exhibits a more occluded periplasmic vestibule than seen in a previous structure of a (different Nb) apo-LacYWW/Nb9039 complex that we argue is caused by sugar-binding, with major differences located at the periplasmic ends of transmembrane helices in the N-terminal half of LacY.}, } @article {pmid30108144, year = {2018}, author = {Marie, C and Clavairoly, A and Frah, M and Hmidan, H and Yan, J and Zhao, C and Van Steenwinckel, J and Daveau, R and Zalc, B and Hassan, B and Thomas, JL and Gressens, P and Ravassard, P and Moszer, I and Martin, DM and Lu, QR and Parras, C}, title = {Oligodendrocyte precursor survival and differentiation requires chromatin remodeling by Chd7 and Chd8.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8246-E8255}, pmid = {30108144}, issn = {1091-6490}, support = {R01 DC009410/DC/NIDCD NIH HHS/United States ; R01 DC014456/DC/NIDCD NIH HHS/United States ; R01 NS072427/NS/NINDS NIH HHS/United States ; R01 NS075243/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Autism Spectrum Disorder/genetics/metabolism/pathology ; CHARGE Syndrome/genetics/metabolism/pathology ; Cell Survival ; *Chromatin Assembly and Disassembly ; DNA-Binding Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Oligodendroglia/*metabolism/pathology ; Stem Cells/*metabolism/pathology ; }, abstract = {Oligodendrocyte precursor cells (OPCs) constitute the main proliferative cells in the adult brain, and deregulation of OPC proliferation-differentiation balance results in either glioma formation or defective adaptive (re)myelination. OPC differentiation requires significant genetic reprogramming, implicating chromatin remodeling. Mounting evidence indicates that chromatin remodelers play important roles during normal development and their mutations are associated with neurodevelopmental defects, with CHD7 haploinsuficiency being the cause of CHARGE syndrome and CHD8 being one of the strongest autism spectrum disorder (ASD) high-risk-associated genes. Herein, we report on uncharacterized functions of the chromatin remodelers Chd7 and Chd8 in OPCs. Their OPC-chromatin binding profile, combined with transcriptome and chromatin accessibility analyses of Chd7-deleted OPCs, demonstrates that Chd7 protects nonproliferative OPCs from apoptosis by chromatin closing and transcriptional repression of p53 Furthermore, Chd7 controls OPC differentiation through chromatin opening and transcriptional activation of key regulators, including Sox10, Nkx2.2, and Gpr17 However, Chd7 is dispensable for oligodendrocyte stage progression, consistent with Chd8 compensatory function, as suggested by their common chromatin-binding profiles and genetic interaction. Finally, CHD7 and CHD8 bind in OPCs to a majority of ASD risk-associated genes, suggesting an implication of oligodendrocyte lineage cells in ASD neurological defects. Our results thus offer new avenues to understand and modulate the CHD7 and CHD8 functions in normal development and disease.}, } @article {pmid30108020, year = {2018}, author = {Feng, Y and Ryan, UM and Xiao, L}, title = {Genetic Diversity and Population Structure of Cryptosporidium.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {997-1011}, doi = {10.1016/j.pt.2018.07.009}, pmid = {30108020}, issn = {1471-5007}, abstract = {Cryptosporidium species differ in host range. Parasite-host coevolution, host adaptation, and geographic segregation have led to the formation of subtype families with unique phenotypic traits within the major human-pathogenic species C. parvum and C. hominis. Transmission intensity, genetic diversity, and occurrence of genetic recombination and selective pressure have further shaped their population genetic structures. Panmixia appears to be common within the zoonotic C. parvum, especially its hypertransmissible IIaA15G2R1 subtype. Genetic recombination in C. hominis, in contrast, is more restricted to virulent subtypes, especially IbA10G2. Nonhuman primates and equine animals are commonly infected with genetically divergent C. hominis populations. Systematic studies of these and other host-adapted Cryptosporidium spp. are likely leading to improved understanding of population structures underlying various transmission patterns and intensities of Cryptosporidium.}, } @article {pmid30107827, year = {2018}, author = {Fernando, GKAW and Jayakody, S and Wijenayake, WMHK and Galappaththy, GNL and Yatawara, M and Harishchandra, J}, title = {A comparison of the larvivorous habits of exotic Poecilia reticulata and native Aplocheilus parvus.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {25}, pmid = {30107827}, issn = {1472-6785}, abstract = {BACKGROUND: The exotic fish Poecilia reticulata is promoted in the tropics as a biological control agent for aquatic pathogenic carriers, such as mosquitoes. Such control measures are often adopted blindly, ignoring the potential of native species and the adverse effects of introduced species. The present study was conducted to assess the diet composition of two species of fish, the native Aplocheilus parvus and exotic P. reticulata, and to assess the availability of food items in their natural environment in four types of aquatic systems. Diet composition was estimated using 24 h gut contents analysis, in a clay quarry pit and a perennial reservoir for A. parvus, and in a man-made canal and a second-order natural stream for P. reticulata. Food items in these environments were quantified by analyzing water samples collected every 2 h.

RESULTS: The diet of A. parvus in the clay quarry pit and reservoir consisted of adult or larval stages of Insecta, Maxillopoda and Malacostraca. In both habitats, A. parvus selectively fed on insect parts and insect larvae. The diet of P. reticulata consisted of filamentous algae, diatoms and detritus. The diet of A. parvus showed active selection of insectivore food items against their low availability. In contrast, the diet of P. reticulata showed consumption of food items in accordance with their availability in the environment. The highest mean number of food items in the gut for A. parvus was recorded around mid-day in the clay quarry pit, but no peak feeding time was identified in the perennial reservoir. For P. reticulata, peak feeding was recorded around mid-day in both the habitats.

CONCLUSION: Irrespective of the type of environment and rate of occurrence, A. parvus preferred insect and insect larvae, whereas P. reticulata consumed the most readily available food items. The active selection of insects by A. parvus suggests they may have value as a biological control agent.}, } @article {pmid30107823, year = {2018}, author = {Naveed, S and Lashari, UG and Waqas, A and Bhuiyan, M and Meraj, H}, title = {Gender of children and social provisions as predictors of unplanned pregnancies in Pakistan: a cross-sectional survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {587}, pmid = {30107823}, issn = {1756-0500}, mesh = {Adult ; Child ; Cross-Sectional Studies ; Family Planning Services ; Female ; Humans ; Pakistan ; Pregnancy ; *Pregnancy, Unplanned ; Reproducibility of Results ; *Social Support ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Previous research indicates that attitudes to pregnancy and motherhood are influenced by social values, culture and religion. This study explores the relationship between social support and unwanted pregnancy among Pakistani women. This cross-sectional study was conducted at four teaching hospitals in Lahore in 2014.

RESULTS: A total of 500 pregnant women who visited the hospitals' obstetrics and gynecology departments were asked to respond to a questionnaire consisting of respondents' characteristics and the Social Provisions Scale (SPS). Logistic regression analyzed the predictors of unplanned pregnancy. Unwanted pregnancies were more likely to occur among pregnant women from rural areas, with low scores on the SPS 'reassurance of worth' sub-scale, no history of contraceptive use, and who already had at least one son than those with no sons.}, } @article {pmid30107822, year = {2018}, author = {Higgoda, R and Lokuketagoda, K and Poobalasingham, T and Wedagedara, V and Perera, D and Thirumavalavan, K}, title = {Dengue fever manifesting with tetany as the first presentation of primary hypoparathyroidism: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {588}, pmid = {30107822}, issn = {1756-0500}, mesh = {Adult ; Dengue/*complications ; Humans ; Hypocalcemia ; Hypoparathyroidism/*complications ; Male ; Sri Lanka ; Tetany/*complications ; }, abstract = {BACKGROUND: Primary hypoparathyroidism is associated with diverse variety of symptomatology of hypocalcemia including seizures and tetany. We report a case of previously undiagnosed asymptomatic primary hypoparathyroidism with extensive basal ganglia calcifications presenting for the first time with hypocalcemic tetany during acute dengue infection. Although hypocalcemia is known to occur in dengue infection symptomatic hypocalcemia is very infrequent.

CASE PRESENTATION: A 32 year old male with short stature who has undergone bilateral cataract surgery 2 years ago but who was otherwise healthy, presented with fever and generalized body aches of 3 days duration and carpal spasms/tetany occurring on the third day of the illness. He was diagnosed to have acute dengue fever along with severe hypocalcemia. Subsequent workup confirmed that the patient had primary hypoparathyroidism with extensive basal ganglia and cerebellar calcifications which was previously undiagnosed. His acute illness and hypocalcemia was managed successfully and was commenced on regular calcium supplementations to alleviate the hypocalcemic effects of his chronic illness.

CONCLUSION: Clinical features of hypocalcemia may not commonly manifest up to the same degree of severity of hypocalcemia in primary hypoparathyroidism even till late adulthood but potential early clues such as short stature and premature cataract should be actively investigated. Worsening of already existing hypocalcemia during acute dengue fever led to the ultimate diagnosis of primary hypoparathyroidism in this patient which was lifesaving.}, } @article {pmid30107818, year = {2018}, author = {Galankin, T and Lioznov, D and Nikolaenko, S and McNutt, LA and Leckman-Westin, E and Smith, PF}, title = {Psychological features of abstinent heroin users before and after rehabilitation in Saint Petersburg, Russia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {589}, pmid = {30107818}, issn = {1756-0500}, mesh = {Heroin ; Heroin Dependence/*psychology/rehabilitation ; Humans ; MMPI ; *Personality ; Personality Disorders ; Russia ; }, abstract = {OBJECTIVE: The objective of the study was to describe psychological features of abstinent heroin users undergoing rehabilitation in Saint Petersburg, Russia. Study subjects (n = 197) were recruited prospectively at the time of their admission to rehabilitation between March 2010 and May 2011 at 7 inpatient opiate addiction rehabilitation centers in Saint-Petersburg and neighboring regions, Russia. The centers provided varying rehabilitation programs; 6 of them were religious centers. Socio-demographic information and self-reported HIV status were collected. Personality profiles and severity of drug-associated problems were estimated before and after rehabilitation using the Minnesota Multiphasic Personality Inventory 2 (MMPI-2), and the Addiction Severity Index (ASI).

RESULTS: Thirty-three (17%) subjects dropped out before completing rehabilitation (non-completers). All subjects (completers and non-completers) had psychopathological personality profiles according to MMPI-2. These profiles were refractory to clinically significant improvement after rehabilitation, although some statistically significant changes toward improvement were observed. ASI scores showed statistically and clinically significant improvements after rehabilitation on all scales. Participants in longer-term versus shorter-term rehabilitation programs showed similar changes in their pre- and post-rehabilitation MMPI-2 and ASI scores. Our results suggest that unmet psychiatric needs should be addressed to potentially improve treatment completion in this population.}, } @article {pmid30107816, year = {2018}, author = {Adam, DC and Bui, CM and Heywood, AE and Kunasekaran, M and Sheikh, M and Narasimhan, P and MacIntyre, CR}, title = {Adherence to anti-vectorial prevention measures among travellers with chikungunya and malaria returning to Australia: comparative epidemiology.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {590}, pmid = {30107816}, issn = {1756-0500}, support = {DP120100189//Australian Research Council/ ; }, mesh = {Africa ; Chikungunya Fever/*prevention & control ; Health Behavior ; Humans ; India ; Indonesia ; *Information Seeking Behavior ; Malaria/*prevention & control ; New South Wales ; Patient Compliance ; *Travel ; Victoria ; }, abstract = {OBJECTIVE: Compare the adoption and adherence to health protection behaviours prior to and during travel among international Australian travellers who return to Australia with notified chikungunya or malaria infection. This information could inform targeted health promotion and intervention strategies to limit the establishment of these diseases within Australia.

RESULTS: Seeking travel advice prior to departure was moderate (46%, N = 21/46) yet compliance with a range of recommended anti-vectorial prevention measures was low among both chikungunya and malaria infected groups (16%, N = 7/45). Reasons for not seeking advice between groups was similar and included 'previous overseas travel with no problems' (45%, N = 9/20) and 'no perceived risk of disease' (20%, N = 4/20). Most chikungunya cases (65%, N = 13/20) travelled to Indonesia and a further 25% (N = 5/20) visited India, however most malaria cases (62%, N = 16/26) travelled to continental Africa with only 12% (N = 3/26) travelling to India. The majority (50%, N = 10/20) of chikungunya cases reported 'holiday' as their primary purpose of travel, compared to malaria cases who most frequently reported travel to visit friends and family (VFR; 42%, N = 11/26). These results provide import data that may be used to support distinct public health promotion and intervention strategies of two important vector-borne infectious diseases of concern for Australia.}, } @article {pmid30107785, year = {2018}, author = {Sobkowiak, B and Glynn, JR and Houben, RMGJ and Mallard, K and Phelan, JE and Guerra-Assunção, JA and Banda, L and Mzembe, T and Viveiros, M and McNerney, R and Parkhill, J and Crampin, AC and Clark, TG}, title = {Identifying mixed Mycobacterium tuberculosis infections from whole genome sequence data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {613}, pmid = {30107785}, issn = {1471-2164}, support = {UID/Multi/04413/2013//Fundação para a Ciência e a Tecnologia/ ; MR/K000551/1//Medical Research Council/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; MR/M01360X/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; MC_PC_15103//Medical Research Council/United Kingdom ; MR/N010469/1//Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Bayes Theorem ; DNA, Bacterial ; Female ; Genome, Bacterial ; Humans ; Male ; Middle Aged ; Mycobacterium tuberculosis/*classification/*genetics/isolation & purification ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/*methods ; Tuberculosis/*diagnosis/genetics/microbiology ; Whole Genome Sequencing/*methods ; Young Adult ; }, abstract = {BACKGROUND: Mixed, polyclonal Mycobacterium tuberculosis infection occurs in natural populations. Developing an effective method for detecting such cases is important in measuring the success of treatment and reconstruction of transmission between patients. Using whole genome sequence (WGS) data, we assess two methods for detecting mixed infection: (i) a combination of the number of heterozygous sites and the proportion of heterozygous sites to total SNPs, and (ii) Bayesian model-based clustering of allele frequencies from sequencing reads at heterozygous sites.

RESULTS: In silico and in vitro artificially mixed and known pure M. tuberculosis samples were analysed to determine the specificity and sensitivity of each method. We found that both approaches were effective in distinguishing between pure strains and mixed infection where there was relatively high (> 10%) proportion of a minor strain in the mixture. A large dataset of clinical isolates (n = 1963) from the Karonga Prevention Study in Northern Malawi was tested to examine correlations with patient characteristics and outcomes with mixed infection. The frequency of mixed infection in the population was found to be around 10%, with an association with year of diagnosis, but no association with age, sex, HIV status or previous tuberculosis.

CONCLUSIONS: Mixed Mycobacterium tuberculosis infection was identified in silico using whole genome sequence data. The methods presented here can be applied to population-wide analyses of tuberculosis to estimate the frequency of mixed infection, and to identify individual cases of mixed infections. These cases are important when considering the evolution and transmission of the disease, and in patient treatment.}, } @article {pmid30107784, year = {2018}, author = {Karash, S and Kwon, YM}, title = {Iron-dependent essential genes in Salmonella Typhimurium.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {610}, pmid = {30107784}, issn = {1471-2164}, mesh = {DNA Transposable Elements ; Gene Expression Regulation, Bacterial/*drug effects ; Genes, Bacterial ; Genes, Essential ; Iron/*pharmacology ; Mutagenesis, Insertional ; Reactive Oxygen Species/metabolism ; Salmonella Infections/*drug therapy/genetics/microbiology ; Salmonella typhimurium/drug effects/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The molecular mechanisms underlying bacterial cell death due to stresses or bactericidal antibiotics are complex and remain puzzling. Due to the current crisis of antibiotic resistance, development of effective antibiotics is urgently required. Previously, it has been shown that iron is required for effective killing of bacterial cells by numerous bactericidal antibiotics.

RESULTS: We investigated the death or growth inhibition of S. Typhimurium under iron-restricted conditions, following disruption of essential genes, by transposon mutagenesis using transposon sequencing (Tn-seq). Our high-resolution Tn-seq analysis revealed that transposon mutants of S. Typhimurium with insertions in essential genes escaped immediate killing or growth inhibition under iron-restricted conditions for approximately one-third of all previously known essential genes. Based on this result, we classified all essential genes into two categories, iron-dependent essential genes, for which the insertion mutants can grow slowly if iron is restricted, and iron-independent essential genes, for which the mutants become nonviable regardless of iron concentration. The iron-dependency of the iron-dependent essential genes was further validated by the fact that the relative abundance of these essential gene mutants increased further with more severe iron restrictions. Our unexpected observation can be explained well by the common killing mechanisms of bactericidal antibiotics via production of reactive oxygen species (ROS). In this model, iron restriction would inhibit production of ROS, leading to reduced killing activity following blocking of essential gene functions. Interestingly, the targets of most antibiotics currently in use clinically are iron-dependent essential genes.

CONCLUSIONS: Our result suggests that targeting iron-independent essential genes may be a better strategy for future antibiotic development, because blocking their essential gene functions would lead to immediate cell death regardless of the iron concentration. This work expands our knowledge on the role of iron to a broad range of essential functions and pathways, providing novel insights for development of more effective antibiotics.}, } @article {pmid30107783, year = {2018}, author = {Cruz-Dávalos, DI and Nieves-Colón, MA and Sockell, A and Poznik, GD and Schroeder, H and Stone, AC and Bustamante, CD and Malaspinas, AS and Ávila-Arcos, MC}, title = {In-solution Y-chromosome capture-enrichment on ancient DNA libraries.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {608}, pmid = {30107783}, issn = {1471-2164}, support = {IA206817//Universidad Nacional Autónoma de México/ ; FP7/2007-2013, grant no. 290344, EUROTAST//European Research Council/International ; }, mesh = {*Chromosomes, Human, Y ; DNA, Ancient/*analysis/*isolation & purification ; *Gene Library ; Genomics ; History, Ancient ; Humans ; Sequence Analysis, DNA/*methods ; Whole Genome Sequencing/*methods ; }, abstract = {BACKGROUND: As most ancient biological samples have low levels of endogenous DNA, it is advantageous to enrich for specific genomic regions prior to sequencing. One approach-in-solution capture-enrichment-retrieves sequences of interest and reduces the fraction of microbial DNA. In this work, we implement a capture-enrichment approach targeting informative regions of the Y chromosome in six human archaeological remains excavated in the Caribbean and dated between 200 and 3000 years BP. We compare the recovery rate of Y-chromosome capture (YCC) alone, whole-genome capture followed by YCC (WGC + YCC) versus non-enriched (pre-capture) libraries.

RESULTS: The six samples show different levels of initial endogenous content, with very low (< 0.05%, 4 samples) or low (0.1-1.54%, 2 samples) percentages of sequenced reads mapping to the human genome. We recover 12-9549 times more targeted unique Y-chromosome sequences after capture, where 0.0-6.2% (WGC + YCC) and 0.0-23.5% (YCC) of the sequence reads were on-target, compared to 0.0-0.00003% pre-capture. In samples with endogenous DNA content greater than 0.1%, we found that WGC followed by YCC (WGC + YCC) yields lower enrichment due to the loss of complexity in consecutive capture experiments, whereas in samples with lower endogenous content, the libraries' initial low complexity leads to minor proportions of Y-chromosome reads. Finally, increasing recovery of informative sites enabled us to assign Y-chromosome haplogroups to some of the archeological remains and gain insights about their paternal lineages and origins.

CONCLUSIONS: We present to our knowledge the first in-solution capture-enrichment method targeting the human Y-chromosome in aDNA sequencing libraries. YCC and WGC + YCC enrichments lead to an increase in the amount of Y-DNA sequences, as compared to libraries not enriched for the Y-chromosome. Our probe design effectively recovers regions of the Y-chromosome bearing phylogenetically informative sites, allowing us to identify paternal lineages with less sequencing than needed for pre-capture libraries. Finally, we recommend considering the endogenous content in the experimental design and avoiding consecutive rounds of capture, as clonality increases considerably with each round.}, } @article {pmid30107782, year = {2018}, author = {Wang, H and Wei, H and Tang, L and Lu, J and Mu, C and Wang, C}, title = {Identification and characterization of miRNAs in the gills of the mud crab (Scylla paramamosain) in response to a sudden drop in salinity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {609}, pmid = {30107782}, issn = {1471-2164}, support = {2016C02055-8//Major Sci & Tech Special Project of Zhejiang Province/ ; CARS-48//China Agriculture Research System-48/ ; XYL18013//Research Fund of Ningbo University/ ; }, mesh = {Animals ; Brachyura/*genetics/physiology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Gene Ontology ; Gills/*physiology ; MicroRNAs/*genetics ; Salinity ; Signal Transduction ; Stress, Physiological ; }, abstract = {BACKGROUND: The mud crab (Scylla paramamosain) is a euryhaline and commercially important species. MiRNAs participate in the regulation of many physiological activities.

RESULTS: The miRNA transcriptome of the gills of S. paramamosain was used to investigate the expression profiles of miRNAs in response to a sudden drop in salinity. In total, seven known miRNAs and 43 novel miRNAs were identified, with 18 differentially expressed small RNAs. Fourteen thousand nine hundred fifty-one differentially expressed miRNAs target genes were screened by prediction. GO analysis of differentially expressed miRNAs target genes indicated that 578 genes associated with cellular processes, 523 associated with metabolic processes, and 422 associated with single-organism processes were the most strongly affected by a sudden drop in salinity from 23‰ to 3‰. KEGG pathway analysis showed 14 pathways were related to amino acid metabolism, which plays an important role in osmoregulation. Besides, several pathways were associated with starch and sucrose metabolism (ko00500), glycosaminoglycan degradation (ko00531), and galactose metabolism (ko00052).

CONCLUSIONS: S. paramamosain regulated osmotic pressure and energy balance by regulating target genes to adapt to a sudden changes in salinity. These results provided a basis for further investigations of miRNA-modulating networks underlying the osmoregulation of S. paramamosain.}, } @article {pmid30107781, year = {2018}, author = {Guo, S and Iqbal, S and Ma, R and Song, J and Yu, M and Gao, Z}, title = {High-density genetic map construction and quantitative trait loci analysis of the stony hard phenotype in peach based on restriction-site associated DNA sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {612}, pmid = {30107781}, issn = {1471-2164}, support = {CARS-30//China Agriculture Research System/ ; CX (15)1020//Jiangsu Agriculture Science and Technology Innovation Fund/ ; NY068//Six Talent Fund of Jiangsu Province/ ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, mesh = {Gene Expression Profiling ; Genetic Association Studies/*methods ; *Polymorphism, Single Nucleotide ; Prunus persica/*genetics ; *Quantitative Trait Loci ; Restriction Mapping ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Peach (Prunus persica) is an important fruit crop that generally softens rapidly after harvest resulting in a short shelf-life. By contrast, stony hard (SH) peach fruit does not soften and hardly produces ethylene. To explore the candidate genes responsible for the SH phenotype, a high-density genetic map was constructed by restriction-site associated DNA sequencing technology.

RESULTS: In the present study, the linkage map consisted of 1310 single nucleotide polymorphism markers, spanning 454.2 cM, with an average marker distance of 0.347 cM. The single nucleotide polymorphisms were able to anchor eight linkage groups to their corresponding chromosomes. Based on this high-density integrated peach linkage map and two years of fruit phenotyping, two potential quantitative trait loci for the SH trait were identified and positioned on the genetic map. Additionally, Prupe.6G150900.1, a key gene in abscisic acid (ABA) biosynthesis, displayed a differential expression profile identical to the ABA accumulation pattern: mRNA transcripts were maintained at a high level during storage of SH peaches but occurred at low levels in melting fruit.

CONCLUSION: Thus Prupe.6G150900.1 might play a crucial role in the SH phenotype of peach in which ABA negatively regulates ethylene production. Also, this high-density linkage map of peach will contribute to the mapping of important fruit traits and quantitative trait loci identification.}, } @article {pmid30107780, year = {2018}, author = {Dong, S and Zhao, C and Chen, F and Liu, Y and Zhang, S and Wu, H and Zhang, L and Liu, Y}, title = {The complete mitochondrial genome of the early flowering plant Nymphaea colorata is highly repetitive with low recombination.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {614}, pmid = {30107780}, issn = {1471-2164}, support = {31470314//National Natural Science Foundation of China/ ; 31600171//National Natural Science Foundation of China/ ; FLSF2017-03//National Natural Science Foundation of China/ ; 201520//Shenzhen Urban Management Bureau Fund/ ; DEB-1240045//National Science Foundation/ ; JCYJ20150529150409546//Shenzhen Municipal Government of China/ ; }, mesh = {*Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing/methods ; Mitochondria/*genetics ; Nymphaea/*genetics/growth & development ; *Recombination, Genetic ; Repetitive Sequences, Nucleic Acid ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Mitochondrial genomes of flowering plants (angiosperms) are highly dynamic in genome structure. The mitogenome of the earliest angiosperm Amborella is remarkable in carrying rampant foreign DNAs, in contrast to Liriodendron, the other only known early angiosperm mitogenome that is described as 'fossilized'. The distinctive features observed in the two early flowering plant mitogenomes add to the current confusions of what early flowering plants look like. Expanded sampling would provide more details in understanding the mitogenomic evolution of early angiosperms. Here we report the complete mitochondrial genome of water lily Nymphaea colorata from Nymphaeales, one of the three orders of the earliest angiosperms.

RESULTS: Assembly of data from Pac-Bio long-read sequencing yielded a circular mitochondria chromosome of 617,195 bp with an average depth of 601×. The genome encoded 41 protein coding genes, 20 tRNA and three rRNA genes with 25 group II introns disrupting 10 protein coding genes. Nearly half of the genome is composed of repeated sequences, which contributed substantially to the intron size expansion, making the gross intron length of the Nymphaea mitochondrial genome one of the longest among angiosperms, including an 11.4-Kb intron in cox2, which is the longest organellar intron reported to date in plants. Nevertheless, repeat mediated homologous recombination is unexpectedly low in Nymphaea evidenced by 74 recombined reads detected from ten recombinationally active repeat pairs among 886,982 repeat pairs examined. Extensive gene order changes were detected in the three early angiosperm mitogenomes, i.e. 38 or 44 events of inversions and translocations are needed to reconcile the mitogenome of Nymphaea with Amborella or Liriodendron, respectively. In contrast to Amborella with six genome equivalents of foreign mitochondrial DNA, not a single horizontal gene transfer event was observed in the Nymphaea mitogenome.

CONCLUSIONS: The Nymphaea mitogenome resembles the other available early angiosperm mitogenomes by a similarly rich 64-coding gene set, and many conserved gene clusters, whereas stands out by its highly repetitive nature and resultant remarkable intron expansions. The low recombination level in Nymphaea provides evidence for the predominant master conformation in vivo with a highly substoichiometric set of rearranged molecules.}, } @article {pmid30107779, year = {2018}, author = {Grandchamp, A and Monget, P}, title = {Synchronous birth is a dominant pattern in receptor-ligand evolution.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {611}, pmid = {30107779}, issn = {1471-2164}, mesh = {Animals ; *Evolution, Molecular ; Humans ; Ligands ; Models, Biological ; Phylogeny ; Protein Binding ; Receptors, Cytoplasmic and Nuclear/chemistry/*genetics ; }, abstract = {BACKGROUND: Interactions between proteins are key components in the chemical and physical processes of living organisms. Among these interactions, membrane receptors and their ligands are particularly important because they are at the interface between extracellular and intracellular environments. Many studies have investigated how binding partners have co-evolved in genomes during the evolution. However, little is known about the establishment of the interaction on a phylogenetic scale. In this study, we systematically studied the time of birth of genes encoding human membrane receptors and their ligands in the animal tree of life. We examined a total of 553 pairs of ligands/receptors, representing non-redundant interactions.

RESULTS: We found that 41% of the receptors and their respective first ligands appeared in the same branch, representing 2.5-fold more than expected by chance, thus suggesting an evolutionary dynamic of interdependence and conservation between these partners. In contrast, 21% of the receptors appeared after their ligand, i.e. three-fold less often than expected by chance. Most surprisingly, 38% of the receptors appeared before their first ligand, as much as expected by chance.

CONCLUSIONS: According to these results, we propose that a selective pressure is exerted on ligands and receptors once they appear, that would remove molecules whose partner does not appear quickly.}, } @article {pmid30107778, year = {2018}, author = {Pericolini, E and Colombari, B and Ferretti, G and Iseppi, R and Ardizzoni, A and Girardis, M and Sala, A and Peppoloni, S and Blasi, E}, title = {Real-time monitoring of Pseudomonas aeruginosa biofilm formation on endotracheal tubes in vitro.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {84}, pmid = {30107778}, issn = {1471-2180}, abstract = {BACKGROUND: Pseudomonas aeruginosa is an opportunistic bacterial pathogen responsible for both acute and chronic infections in humans. In particular, its ability to form biofilm, on biotic and abiotic surfaces, makes it particularly resistant to host's immune defenses and current antibiotic therapies as well. Innovative antimicrobial materials, like hydrogel, silver salts or nanoparticles have been used to cover new generation catheters with promising results. Nevertheless, biofilm remains a major health problem. For instance, biofilm produced onto endotracheal tubes (ETT) of ventilated patients plays a relevant role in the onset of ventilation-associated pneumonia. Most of our knowledge on Pseudomonas aeruginosa biofilm derives from in vitro studies carried out on abiotic surfaces, such as polystyrene microplates or plastic materials used for ETT manufacturing. However, these approaches often provide underestimated results since other parameters, in addition to bacterial features (i.e. shape and material composition of ETT) might strongly influence biofilm formation.

RESULTS: We used an already established biofilm development assay on medically-relevant foreign devices (CVC catheters) by a stably transformed bioluminescent (BLI)-Pseudomonas aeruginosa strain, in order to follow up biofilm formation on ETT by bioluminescence detection. Our results demonstrated that it is possible: i) to monitor BLI-Pseudomonas aeruginosa biofilm development on ETT pieces in real-time, ii) to evaluate the three-dimensional structure of biofilm directly on ETT, iii) to assess metabolic behavior and the production of microbial virulence traits of bacteria embedded on ETT-biofilm.

CONCLUSIONS: Overall, we were able to standardize a rapid and easy-to-perform in vitro model for real-time monitoring Pseudomonas aeruginosa biofilm formation directly onto ETT pieces, taking into account not only microbial factors, but also ETT shape and material. Our study provides a rapid method for future screening and validation of novel antimicrobial drugs as well as for the evaluation of novel biomaterials employed in the production of new classes of ETT.}, } @article {pmid30107777, year = {2018}, author = {Płuciennik, A and Stolarczyk, M and Bzówka, M and Raczyńska, A and Magdziarz, T and Góra, A}, title = {BALCONY: an R package for MSA and functional compartments of protein variability analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {300}, pmid = {30107777}, issn = {1471-2105}, support = {DEC-2013/10/E/NZ1/00649//Narodowe Centrum Nauki/ ; }, abstract = {BACKGROUND: Here, we present an R package for entropy/variability analysis that facilitates prompt and convenient data extraction, manipulation and visualization of protein features from multiple sequence alignments. BALCONY can work with residues dispersed across a protein sequence and map them on the corresponding alignment of homologous protein sequences. Additionally, it provides several entropy and variability scores that indicate the conservation of each residue.

RESULTS: Our package allows the user to visualize evolutionary variability by locating the positions most likely to vary and to assess mutation candidates in protein engineering.

CONCLUSION: In comparison to other R packages BALCONY allows conservation/variability analysis in context of protein structure with linkage of the appropriate metrics with physicochemical features of user choice.

AVAILABILITY: CRAN project page: https://cran.r-project.org/package=BALCONY and our website: http://www.tunnelinggroup.pl/software/ for major platforms: Linux/Unix, Windows and Mac OS X.}, } @article {pmid30107579, year = {2018}, author = {Flatau, R and Segoli, M and Khokhlova, I and Hawlena, H}, title = {Wolbachia's role in mediating its flea's reproductive success differs according to flea origin.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy157}, pmid = {30107579}, issn = {1574-6941}, abstract = {Endosymbionts-microbes that live within and engage in prolonged and intimate associations with their hosts-are gaining recognition for their direct impact on plant and animal reproduction. Here we used the overlooked Wolbachia-flea system to explore the possibility that endosymbionts may also play a role as mediators in shaping the reproductive success of their hosts. We simultaneously quantified the Wolbachia density in field- and laboratory-originated fleas that fed and mated on rodents for either 5 or 10 days and assessed their body size and current reproductive success. By combining multigroup analysis and model selection approaches, we teased apart the contribution of the direct effects of the flea's physiological age and body size and the mediation effect of its Wolbachia endosymbionts on flea reproductive success, and we showed that the latter was stronger than the former. However, interestingly, the mediation effect was manifested only in laboratory-originated fleas, for which the increase in Wolbachia with age translated into lower reproductive success. These results suggest that some well-supported phenomena, such as aging effects, may be driven by endosymbionts and show once again that the role of endosymbionts in shaping the reproductive success of their host depends on their selective environment.}, } @article {pmid30107549, year = {2018}, author = {Le, HT and Rochelle-Newall, E and Auda, Y and Ribolzi, O and Sengtaheuanghoung, O and Thébault, E and Soulileuth, B and Pommier, T}, title = {Vicinal land use change strongly drives stream bacterial community in a tropical montane catchment.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy155}, pmid = {30107549}, issn = {1574-6941}, abstract = {Impact of land use (LU) change on stream environmental conditions and the inhabiting bacterial community remains rarely investigated, especially in tropical montane catchments. We examined the effects of LU change and its legacy along a tropical stream by comparing seasonal patterns of dissolved organic carbon (DOC) / colored dissolved organic matter (CDOM) in relation to variations in structure, diversity and metabolic capacities of particle-attached (PA) and free-living (FL) bacterial communities. We hypothesized that despite seasonal differences, hydrological flows that accumulate allochthonous carbon along the catchment are a major controlling factor of the bacterial community. Surprisingly, local environmental conditions that were largely related to nearby LU and the legacy of LU change were more important for stream bacterial diversity than hydrological connectivity. DOC was strongly correlated with PA richness and diversity. The legacy of LU change between teak plantation and annual crops induced high DOC and high diversity and richness of PA in the adjacent waters, while banana plantations were associated with high diversity of FL. The community structures of both PA and FL differed significantly between seasons. Our results highlight the importance of vicinal LU change and its legacy on aquatic bacterial communities in mixed used tropical watersheds.}, } @article {pmid30107505, year = {2018}, author = {Belinchón, R and Ellis, CJ and Yahr, R}, title = {Climate-woodland effects on population genetics for two congeneric lichens with contrasting reproductive strategies.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, doi = {10.1093/femsec/fiy159}, pmid = {30107505}, issn = {1574-6941}, abstract = {Genetic variation is expected to be influenced by the interaction between reproductive mode and dispersal traits on the one hand and environmental and habitat setting affecting establishment success on the other. We evaluated how environmental/habitat setting affects population genetic variation (i.e. variation in genetic diversity and structure) when regulated by contrasting dispersal traits. We used fungus-specific microsatellite markers to examine genetic diversity and structure of two closely related epiphytic lichen fungi that differ in their primary reproductive mode: Nephroma laevigatum (sexually reproducing, n = 191, 10 microsatellites) and N. parile (asexually reproducing, n = 182, 12 microsatellites), along a steep climatic gradient in Scotland. Despite their reproductive differences, we found a high proportion of clones in both species and a background pattern of genetic structure related to climatic gradients. We also demonstrated that woodland connectivity, rather than geographic distance, explained genetic diversity in both species. Environmental/habitat setting, modulated by the reproductive mode of the species, affects genetic diversity and structure, but the putative dissimilarity in their reproductive mode is less important than has been previously assumed. We reinforce the importance of protecting highly connected populations, positioned along a gradient capturing the segregation of gene pool differences in response to climatic variation.}, } @article {pmid30107498, year = {2018}, author = {Smith, RJ and Paterson, JS and Wallis, I and Launer, E and Banks, EW and Bresciani, E and Cranswick, RH and Tobe, SS and Marri, S and Goonan, P and Mitchell, JG}, title = {Southern South Australian groundwater microbe diversity.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy158}, pmid = {30107498}, issn = {1574-6941}, abstract = {Groundwater is increasingly used globally for domestic, industrial and agricultural production. While many studies have focused on groundwater as a resource, the diverse ecosystems within are often ignored. Here, we assess 54 Southern South Australian groundwater microbial communities from the populated part of the state to assess their status and dynamics in isolated groundwater systems. We observed a strong site-to-site individuality in groundwater bacterial communities, likely due to the isolated nature of groundwater bodies leading to unique ecosystems. Rank abundance analysis indicates bacterial diversity is maintained even at low abundances and that the distribution fits classical ecological models for strong competition in resource-limited environments. Combined, our data indicates that despite overrepresentation of pollutant-associated bacterial orders in and around the Adelaide metropolitan area, microbial communities remain diverse and show little evidence of converging on a common pollutant-effected community.}, } @article {pmid30107398, year = {2018}, author = {Han, FR and Guang, XM and Wan, QH and Fang, SG}, title = {Deep Sequencing of Fosmid Clones Indicates Gene Conversion in the Male-Specific Region of the Giant Panda Y Chromosome.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2168-2177}, pmid = {30107398}, issn = {1759-6653}, abstract = {The giant panda (Ailuropoda melanoleuca) is popular around the world and is widely recognized as a symbol of nature conservation. A draft genome of the giant panda is now available, but its Y chromosome has not been sequenced. Y chromosome data are necessary for study of sex chromosome evolution, male development, and spermatogenesis. Thus, in the present study, we sequenced two parts of the giant panda Y chromosome utilizing a male giant panda fosmid library. The sequencing data were assembled into two contigs, each ∼100 kb in length with no gaps, providing high-quality resources for studying the giant panda Y chromosome. Annotation and transposable element comparison indicates varied evolutionary pressure in different regions of the Y chromosome. Two genes, zinc finger protein, Y-linked (ZFY) and lysine demethylase 5D (KDM5D), were annotated and gene conversion was observed for ZFY exon 7. Phylogenetic analysis also revealed that this gene conversion event happened independently in multiple mammalian lineages, indicating a putative mechanism to maintain the function of this particular gene on the Y chromosome. Furthermore, a transposition event, discovered through comparative alignment with the giant panda X chromosome sequence, may be involved in the process of gaining new genes on the Y chromosome. Thus, these newly obtained Y chromosome sequences provide valuable insights into the genomic patterns of the giant panda.}, } @article {pmid30107064, year = {2018}, author = {Gates, DE and Valletta, JJ and Bonneaud, C and Recker, M}, title = {Quantitative host resistance drives the evolution of increased virulence in an emerging pathogen.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1704-1714}, doi = {10.1111/jeb.13366}, pmid = {30107064}, issn = {1420-9101}, abstract = {Emergent infectious diseases can have a devastating impact on host populations. The high selective pressures on both the hosts and the pathogens frequently lead to rapid adaptations not only in pathogen virulence but also host resistance following an initial outbreak. However, it is often unclear whether hosts will evolve to avoid infection-associated fitness costs by preventing the establishment of infection (here referred to as qualitative resistance) or by limiting its deleterious effects through immune functioning (here referred to as quantitative resistance). Equally, the evolutionary repercussions these different resistance mechanisms have for the pathogen are often unknown. Here, we investigate the co-evolutionary dynamics of pathogen virulence and host resistance following the epizootic outbreak of the highly pathogenic bacterium Mycoplasma gallisepticum in North American house finches (Haemorhous mexicanus). Using an evolutionary modelling approach and with a specific emphasis on the evolved resistance trait, we demonstrate that the rapid increase in the frequency of resistant birds following the outbreak is indicative of strong selection pressure to reduce infection-associated mortality. This, in turn, created the ecological conditions that selected for increased bacterial virulence. Our results thus suggest that quantitative host resistance was the key factor underlying the evolutionary interactions in this natural host-pathogen system.}, } @article {pmid30107046, year = {2018}, author = {Ponzi, E and Keller, LF and Bonnet, T and Muff, S}, title = {Heritability, selection, and the response to selection in the presence of phenotypic measurement error: Effects, cures, and the role of repeated measurements.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {1992-2004}, doi = {10.1111/evo.13573}, pmid = {30107046}, issn = {1558-5646}, support = {FK-16-097//Universität Zürich/ ; 31003A 141110//Swiss National Science Foundation/ ; 31003A 159462/1//Swiss National Science Foundation/ ; }, abstract = {Quantitative genetic analyses require extensive measurements of phenotypic traits, a task that is often not trivial, especially in wild populations. On top of instrumental measurement error, some traits may undergo transient (i.e., nonpersistent) fluctuations that are biologically irrelevant for selection processes. These two sources of variability, which we denote here as measurement error in a broad sense, are possible causes for bias in the estimation of quantitative genetic parameters. We illustrate how in a continuous trait transient effects with a classical measurement error structure may bias estimates of heritability, selection gradients, and the predicted response to selection. We propose strategies to obtain unbiased estimates with the help of repeated measurements taken at an appropriate temporal scale. However, the fact that in quantitative genetic analyses repeated measurements are also used to isolate permanent environmental instead of transient effects requires that the information content of repeated measurements is carefully assessed. To this end, we propose to distinguish "short-term" from "long-term" repeats, where the former capture transient variability and the latter help isolate permanent effects. We show how the inclusion of the corresponding variance components in quantitative genetic models yields unbiased estimates of all quantities of interest, and we illustrate the application of the method to data from a Swiss snow vole population.}, } @article {pmid30106224, year = {2018}, author = {Otwell, AE and López García de Lomana, A and Gibbons, SM and Orellana, MV and Baliga, NS}, title = {Systems biology approaches towards predictive microbial ecology.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4197-4209}, doi = {10.1111/1462-2920.14378}, pmid = {30106224}, issn = {1462-2920}, support = {//Washington Research Foundation/ ; //Office of Science/ ; //U.S. Department of Energy/ ; //Lawrence Berkeley National Laboratory/ ; //National Science Foundation/ ; }, abstract = {Through complex interspecies interactions, microbial processes drive nutrient cycling and biogeochemistry. However, we still struggle to predict specifically which organisms, communities and biotic and abiotic processes are determining ecosystem function and how environmental changes will alter their roles and stability. While the tools to create such a predictive microbial ecology capability exist, cross-disciplinary integration of high-resolution field measurements, detailed laboratory studies and computation is essential. In this perspective, we emphasize the importance of pursuing a multiscale, systems approach to iteratively link ecological processes measured in the field to testable hypotheses that drive high-throughput laboratory experimentation. Mechanistic understanding of microbial processes gained in controlled lab systems will lead to the development of theory that can be tested back in the field. Using N2 O production as an example, we review the current status of field and laboratory research and layout a plausible path to the kind of integration that is needed to enable prediction of how N-cycling microbial communities will respond to environmental changes. We advocate for the development of realistic and predictive gene regulatory network models for environmental responses that extend from single-cell resolution to ecosystems, which is essential to understand how microbial communities involved in N2 O production and consumption will respond to future environmental conditions.}, } @article {pmid30105886, year = {2018}, author = {Zheng, H and Li, L and Miao, P and Wu, C and Chen, X and Yuan, M and Fang, T and Norvienyeku, J and Li, G and Zheng, W and Wang, Z and Zhou, J}, title = {FgSec2A, a guanine nucleotide exchange factor of FgRab8, is important for polarized growth, pathogenicity and deoxynivalenol production in Fusarium graminearum.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3378-3392}, doi = {10.1111/1462-2920.14373}, pmid = {30105886}, issn = {1462-2920}, support = {KXB16010A//FAFU international cooperation project/ ; 31670142//National Natural Science Foundation of China/ ; 31701742//National Natural Science Foundation of China/ ; 2017M622046//China Postdoctoral Science Foundation/ ; }, abstract = {Sec4/Rab8 is one of the well-studied members of the Rab GTPase family, previous studies have shown that Sec4/Rab8 crucially promotes the pathogenesis of phytopathogens, but the upstream regulators of Rab8 are still unknown. Here, we have identified two Sec2 homologues FgSec2A and FgSec2B in devastating fungal pathogen Fusarium graminearum and investigated their functions and interactions with FgRab8 by live-cell imaging, genetic and functional analyses. Yeast two-hybrid assay shows that FgSec2A specifically interacts with FgRab8DN(N123I) and itself. Importantly, FgSec2A is required for growth, conidiation, DON production and virulence of F. graminearum. Live-cell imaging shows that FgSec2A and FgSec2B are both localized to the tip region of hyphae and conidia. Both N-terminal region and Sec2 domain of FgSec2A are essential for its function, but not for localization, whereas the C-terminal region is important for its polarized localization. Furthermore, constitutively active FgRab8CA(Q69L) partially rescues the defects of ΔFgsec2A. Consistently, FgSec2A is required for the polarized localization of FgRab8. Finally, FgSec2A and FgSec2B show partial functions, but FgSec2A does not interact and co-localize with FgSec2B. Taken together, these results indicate that FgSec2A acts as a FgRab8 guanine nucleotide exchange factor and is necessary for polarized growth, DON production and pathogenicity in F. graminearum.}, } @article {pmid30105856, year = {2018}, author = {Halbwachs, H and Easton, GL and Bol, R and Hobbie, EA and Garnett, MH and Peršoh, D and Dixon, L and Ostle, N and Karasch, P and Griffith, GW}, title = {Isotopic evidence of biotrophy and unusual nitrogen nutrition in soil-dwelling Hygrophoraceae.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3573-3588}, doi = {10.1111/1462-2920.14327}, pmid = {30105856}, issn = {1462-2920}, support = {NER/T/S/2001/00143//Natural Environment Research Council/ ; NRCF010001//NERC Radiocarbon Facility/ ; }, abstract = {Several lines of evidence suggest that the agaricoid, non-ectomycorrhizal members of the family Hygrophoraceae (waxcaps) are biotrophic with unusual nitrogen nutrition. However, methods for the axenic culture and lab-based study of these organisms remain to be developed, so our current knowledge is limited to field-based investigations. Addition of nitrogen, lime or organophosphate pesticide at an experimental field site (Sourhope) suppressed fruiting of waxcap basidiocarps. Furthermore, stable isotope natural abundance in basidiocarps were unusually high in 15 N and low in 13 C, the latter consistent with mycorrhizal nutritional status. Similar patterns were found in waxcap basidiocarps from diverse habitats across four continents. Additional data from 14 C analysis of basidiocarps and 13 C pulse label experiments suggest that these fungi are not saprotrophs but rather biotrophic endophytes and possibly mycorrhizal. The consistently high but variable δ15 N values (10-20‰) of basidiocarps further indicate that N acquisition or processing differ from other fungi; we suggest that N may be derived from acquisition of N via soil fauna high in the food chain.}, } @article {pmid30105823, year = {2018}, author = {Eizaguirre, JI and Peris, D and Rodríguez, ME and Lopes, CA and De Los Ríos, P and Hittinger, CT and Libkind, D}, title = {Phylogeography of the wild Lager-brewing ancestor (Saccharomyces eubayanus) in Patagonia.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3732-3743}, doi = {10.1111/1462-2920.14375}, pmid = {30105823}, issn = {1462-2920}, support = {PICT1198PICT2014-2542PICT2014-3677//Agencia Nacional de Promoción Científica y Tecnológica/ ; PICT2014-2542//Agencia Nacional de Promoción Científica y Tecnológica/ ; PICT2014-3677//Agencia Nacional de Promoción Científica y Tecnológica/ ; //the Pew Charitable Trusts/ ; //the DOE Great Lakes Bioenergy Research Center/ ; //the Wisconsin Alumni Research Foundation/ ; DEB-1253634//National Science Foundation/ ; PIN04-A128//CONICET/ ; PIP 555//CONICET/ ; PICT 1198//CONICET/ ; PIP392//CONICET/ ; Project B199//Universidad Nacional del Comahue/ ; }, abstract = {Saccharomyces eubayanus is the close relative of the Lager-brewing yeast and was firstly found in North Patagonia associated with Nothofagus trees. In recent years additional strains were found in North America, Asia and New Zealand, and genomic analyses showed the existence of two main populations of this yeast, both of them present in Patagonia. Here, we performed the most comprehensive study of S. eubayanus in Patagonia natural environments (400 samples) and confirmed that this region has the highest isolation success rate for this species described worldwide (more than 10-fold). The genetic characterization of 200 isolates (COX2, DCR1, intFR) revealed five geographically structured subpopulations. We hypothesized that marine ingressions and glaciations, which shaped the Patagonian landscape, contributed on population differentiation. The first large screening of fermentation performance of 60 wild S. eubayanus strains indicated which subpopulations would be more suitable for beer production.}, } @article {pmid30105784, year = {2018}, author = {Rüffel, V and Maar, M and Dammbrück, MN and Hauröder, B and Neu, TR and Meier, J}, title = {Thermodesulfobium sp. strain 3baa, an acidophilic sulfate reducing bacterium forming biofilms triggered by mineral precipitation.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3717-3731}, doi = {10.1111/1462-2920.14374}, pmid = {30105784}, issn = {1462-2920}, abstract = {Sulfate reducing prokaryotes are promising candidates for the remediation of acidic metal-rich waste waters. However, only few acidophilic species have been described to date. Chemolithoautotrophic strain 3baa was isolated from sediments of an acidic mine pit lake. Based on its 16S-rRNA gene sequence it belongs to the genus Thermodesulfobium. It was identified as an acidophile growing in artificial pore water medium in the range of pH 2.6-6.6. Though the highest sulfate reduction rates were obtained at the lower end of this range, elongated cells and extended lag phases demonstrated acid stress. Sulfate reduction at low pH was accompanied by the formation of mineral precipitates strongly adhering to solid surfaces. A structural investigation by laser scanning microscopy, electron microscopy and X-ray microanalysis revealed the formation of Al hydroxides and Fe sulfides which were densely populated by cells. Al hydroxides precipitated first, enabling initial cell attachment. Colonization of solid surfaces coincided with increased sulfate reducing activity indicating more favourable growth conditions within biofilms compared with free-living cells. These findings point out the importance of cell-mineral interaction for biofilm formation and contribute to our understanding how sulfate reducing prokaryotes thrive in both natural and engineered systems at low pH.}, } @article {pmid30105774, year = {2018}, author = {Lee, WY and Bachtiar, M and Choo, CCS and Lee, CG}, title = {Comprehensive review of Hepatitis B Virus-associated hepatocellular carcinoma research through text mining and big data analytics.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12457}, pmid = {30105774}, issn = {1469-185X}, abstract = {PubMed was text mined to glean insights into the role of Hepatitis B virus (HBV) in hepatocellular carcinoma (HCC) from the massive number of publications (9249) available to date. Reports from ∼70 countries identified >1300 human genes associated with either the Core, Surface or X gene in HBV-associated HCC. One hundred and forty-three of these host genes, which can potentially yield 1180 biomolecular interactions, each were reported in at least three different publications to be associated with the same HBV. These 143 genes function in 137 pathways, involved mainly in the cell cycle, apoptosis, inflammation and signalling. Fourteen of these molecules, primarily transcriptional regulators or kinases, play roles in several pathways pertinent to the hallmarks of cancers. 'Chronic' was the most frequent word used across the 9249 abstracts. A key event in chronic HBV infection is the integration of HBV into the host genome. The advent of cost-effective, next-generation sequencing technology facilitated the employment of big-data analytics comprehensively to characterize HBV-host integration within HCC patients. A total of 5331 integration events were reported across seven publications, with most of these integrations observed between the Core/X gene and the introns of genes. Nearly one-quarter of the intergenic integrations are within repeats, especially long interspersed nuclear elements (LINE) repeats. Integrations within 13 genes were each reported by at least three different studies. The human gene with the most HBV integrations observed is the TERT gene where a total of 224 integrations, primarily at its promoter and within the tumour tissue, were reported by six of seven publications. This unique review, which employs state-of-the-art text-mining and data-analytics tools, represents the most complete, systematic and comprehensive review of nearly all the publications associated with HBV-associated HCC research. It provides important resources to either focus future research or develop therapeutic strategies to target key molecules reported to play important roles in key pathways of HCC, through the systematic analyses of the commonly reported molecules associated with the various HBV genes in HCC, including information about the interactions amongst these commonly reported molecules, the pathways in which they reside as well as detailed information regarding the viral and host genes associated with HBV integration in HCC patients. Hence this review, which highlights pathways and key human genes associated with HBV in HCC, may facilitate the deeper elucidation of the role of HBV in hepato-carcinogenesis, potentially leading to timely intervention against this deadly disease.}, } @article {pmid30105586, year = {2018}, author = {Rahman, MM and Matsumura, S and Ikawa, Y}, title = {Oligomerization of a Bimolecular Ribozyme Modestly Rescues its Structural Defects that Disturb Interdomain Assembly to Form the Catalytic Site.}, journal = {Journal of molecular evolution}, volume = {86}, number = {7}, pages = {431-442}, pmid = {30105586}, issn = {1432-1432}, support = {KAKENHI JP15K05561//Ministry of Education, Culture, Sports, Science and Technology/ ; }, abstract = {The emergence of cellular compartmentalization was a crucial step in the hypothetical RNA world and its evolution because it would not only prevent the extinction of RNA self-replication systems due to dispersion/diffusion of their components but also facilitate ribozyme reactions by molecular crowding effects. Here, we proposed and examined self-assembly of RNA components as a primitive cellular-like environment, which may have the ability to mimic cellular compartmentalization and crowding effects. We engineered a bimolecular group I ribozyme to form a one-dimensional (1D)-ribozyme assembly. In the 1D assembly form, severe mutations that inactivated the parent bimolecular ribozyme were modestly rescued resulting in weak catalytic ability.}, } @article {pmid30105525, year = {2018}, author = {Alwazeer, D and Riondet, C and Cachon, R}, title = {Comparison Between Fluorescent Probe and Ion-Selective Electrode Methods for Intracellular pH Determination in Leuconostoc mesenteroides.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1493-1497}, pmid = {30105525}, issn = {1432-0991}, mesh = {Electrochemical Techniques/instrumentation/*methods ; Fluoresceins/chemistry ; Fluorescent Dyes/*chemistry ; Hydrogen-Ion Concentration ; Ion-Selective Electrodes ; Leuconostoc mesenteroides/*chemistry ; Luminescent Measurements/instrumentation/*methods ; Salicylic Acid/chemistry ; Succinimides/chemistry ; }, abstract = {The intracellular pH (pHin) of Leuconostoc mesenteroides subsp. mesenteroides 19D was evaluated by two different methods, fluorescent probe and ion-selective electrode. Two fluorescent probes 5 (and-6)-carboxyfluorescein diacetate succinimidyl ester (cFDASE) and 5 (and-6)-carboxy-2',7'-dichlorofluorescein diacetate succinimidyl ester (cDCFDASE) were tested to evaluate the intracellular pH (pHin) of living cells at a medium pH (pHex) ranged from 5.0 to 6.5. Salicylic acid was used as a probe for the ion-selective electrode method. Cells kept 60-80% of cFDASE probe at all pHex values against 5-10% of cDCFDASE probe at pHex ≤ 6.0. The pHin values measured by the ion-selective electrode were higher by 0.1-0.6 pH units at pHex ranged from 5.0 to 6.5 than those determinated by fluorescent probe method. The possibility to study the intracellular pH at a wide external pH range using a single probe, and the simplicity of the material and experimental protocol may make the ion-selective electrode method most useful and easy to measure the intracellular pH of lactic acid bacteria compared with the other techniques like fluorescent probes.}, } @article {pmid30104764, year = {2018}, author = {Young, AI and Frigge, ML and Gudbjartsson, DF and Thorleifsson, G and Bjornsdottir, G and Sulem, P and Masson, G and Thorsteinsdottir, U and Stefansson, K and Kong, A}, title = {Relatedness disequilibrium regression estimates heritability without environmental bias.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1304-1310}, pmid = {30104764}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Heritability measures the proportion of trait variation that is due to genetic inheritance. Measurement of heritability is important in the nature-versus-nurture debate. However, existing estimates of heritability may be biased by environmental effects. Here, we introduce relatedness disequilibrium regression (RDR), a novel method for estimating heritability. RDR avoids most sources of environmental bias by exploiting variation in relatedness due to random Mendelian segregation. We used a sample of 54,888 Icelanders who had both parents genotyped to estimate the heritability of 14 traits, including height (55.4%, s.e. 4.4%) and educational attainment (17.0%, s.e. 9.4%). Our results suggest that some other estimates of heritability may be inflated by environmental effects.}, } @article {pmid30104763, year = {2018}, author = {Macintyre, G and Goranova, TE and De Silva, D and Ennis, D and Piskorz, AM and Eldridge, M and Sie, D and Lewsley, LA and Hanif, A and Wilson, C and Dowson, S and Glasspool, RM and Lockley, M and Brockbank, E and Montes, A and Walther, A and Sundar, S and Edmondson, R and Hall, GD and Clamp, A and Gourley, C and Hall, M and Fotopoulou, C and Gabra, H and Paul, J and Supernat, A and Millan, D and Hoyle, A and Bryson, G and Nourse, C and Mincarelli, L and Sanchez, LN and Ylstra, B and Jimenez-Linan, M and Moore, L and Hofmann, O and Markowetz, F and McNeish, IA and Brenton, JD}, title = {Copy number signatures and mutational processes in ovarian carcinoma.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1262-1270}, pmid = {30104763}, issn = {1546-1718}, abstract = {The genomic complexity of profound copy number aberrations has prevented effective molecular stratification of ovarian cancers. Here, to decode this complexity, we derived copy number signatures from shallow whole-genome sequencing of 117 high-grade serous ovarian cancer (HGSOC) cases, which were validated on 527 independent cases. We show that HGSOC comprises a continuum of genomes shaped by multiple mutational processes that result in known patterns of genomic aberration. Copy number signature exposures at diagnosis predict both overall survival and the probability of platinum-resistant relapse. Measurement of signature exposures provides a rational framework to choose combination treatments that target multiple mutational processes.}, } @article {pmid30104762, year = {2018}, author = {Khera, AV and Chaffin, M and Aragam, KG and Haas, ME and Roselli, C and Choi, SH and Natarajan, P and Lander, ES and Lubitz, SA and Ellinor, PT and Kathiresan, S}, title = {Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1219-1224}, pmid = {30104762}, issn = {1546-1718}, support = {KL2 TR001100/TR/NCATS NIH HHS/United States ; R01 HL139731/HL/NHLBI NIH HHS/United States ; K24 HL105780/HL/NHLBI NIH HHS/United States ; UM1 HG008895/HG/NHGRI NIH HHS/United States ; R01 HL092577/HL/NHLBI NIH HHS/United States ; R01 HL127564/HL/NHLBI NIH HHS/United States ; R01 HL128914/HL/NHLBI NIH HHS/United States ; T32 HL007208/HL/NHLBI NIH HHS/United States ; K08 HL140203/HL/NHLBI NIH HHS/United States ; 2014105//Doris Duke Charitable Foundation/United States ; K23 HL114724/HL/NHLBI NIH HHS/United States ; }, abstract = {A key public health need is to identify individuals at high risk for a given disease to enable enhanced screening or preventive therapies. Because most common diseases have a genetic component, one important approach is to stratify individuals based on inherited DNA variation1. Proposed clinical applications have largely focused on finding carriers of rare monogenic mutations at several-fold increased risk. Although most disease risk is polygenic in nature2-5, it has not yet been possible to use polygenic predictors to identify individuals at risk comparable to monogenic mutations. Here, we develop and validate genome-wide polygenic scores for five common diseases. The approach identifies 8.0, 6.1, 3.5, 3.2, and 1.5% of the population at greater than threefold increased risk for coronary artery disease, atrial fibrillation, type 2 diabetes, inflammatory bowel disease, and breast cancer, respectively. For coronary artery disease, this prevalence is 20-fold higher than the carrier frequency of rare monogenic mutations conferring comparable risk6. We propose that it is time to contemplate the inclusion of polygenic risk prediction in clinical care, and discuss relevant issues.}, } @article {pmid30104761, year = {2018}, author = {Zhou, W and Nielsen, JB and Fritsche, LG and Dey, R and Gabrielsen, ME and Wolford, BN and LeFaive, J and VandeHaar, P and Gagliano, SA and Gifford, A and Bastarache, LA and Wei, WQ and Denny, JC and Lin, M and Hveem, K and Kang, HM and Abecasis, GR and Willer, CJ and Lee, S}, title = {Efficiently controlling for case-control imbalance and sample relatedness in large-scale genetic association studies.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1335-1341}, pmid = {30104761}, issn = {1546-1718}, support = {U2C OD023196/OD/NIH HHS/United States ; R01 LM010685/LM/NLM NIH HHS/United States ; R01 HG008773/HG/NHGRI NIH HHS/United States ; R35 HL135824/HL/NHLBI NIH HHS/United States ; R01 HL133786/HL/NHLBI NIH HHS/United States ; }, abstract = {In genome-wide association studies (GWAS) for thousands of phenotypes in large biobanks, most binary traits have substantially fewer cases than controls. Both of the widely used approaches, the linear mixed model and the recently proposed logistic mixed model, perform poorly; they produce large type I error rates when used to analyze unbalanced case-control phenotypes. Here we propose a scalable and accurate generalized mixed model association test that uses the saddlepoint approximation to calibrate the distribution of score test statistics. This method, SAIGE (Scalable and Accurate Implementation of GEneralized mixed model), provides accurate P values even when case-control ratios are extremely unbalanced. SAIGE uses state-of-art optimization strategies to reduce computational costs; hence, it is applicable to GWAS for thousands of phenotypes by large biobanks. Through the analysis of UK Biobank data of 408,961 samples from white British participants with European ancestry for > 1,400 binary phenotypes, we show that SAIGE can efficiently analyze large sample data, controlling for unbalanced case-control ratios and sample relatedness.}, } @article {pmid30104760, year = {2018}, author = {Zhang, Y and Qi, G and Park, JH and Chatterjee, N}, title = {Estimation of complex effect-size distributions using summary-level statistics from genome-wide association studies across 32 complex traits.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1318-1326}, doi = {10.1038/s41588-018-0193-x}, pmid = {30104760}, issn = {1546-1718}, abstract = {We developed a likelihood-based approach for analyzing summary-level statistics and external linkage disequilibrium information to estimate effect-size distributions of common variants, characterized by the proportion of underlying susceptibility SNPs and a flexible normal-mixture model for their effects. Analysis of results available across 32 genome-wide association studies showed that, while all traits are highly polygenic, there is wide diversity in the degree and nature of polygenicity. Psychiatric diseases and traits related to mental health and ability appear to be most polygenic, involving a continuum of small effects. Most other traits, including major chronic diseases, involve clusters of SNPs that have distinct magnitudes of effects. We predict that the sample sizes needed to identify SNPs that explain most heritability found in genome-wide association studies will range from a few hundred thousand to multiple millions, depending on the underlying effect-size distributions of the traits. Accordingly, we project the risk-prediction ability of polygenic risk scores across a wide variety of diseases.}, } @article {pmid30104759, year = {2018}, author = {Palamara, PF and Terhorst, J and Song, YS and Price, AL}, title = {High-throughput inference of pairwise coalescence times identifies signals of selection and enriched disease heritability.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1311-1317}, pmid = {30104759}, issn = {1546-1718}, support = {R01 HG006399/HG/NHGRI NIH HHS/United States ; R01 GM105857/GM/NIGMS NIH HHS/United States ; U01 HG009379/HG/NHGRI NIH HHS/United States ; R01 MH101244/MH/NIMH NIH HHS/United States ; R01 GM094402/GM/NIGMS NIH HHS/United States ; }, abstract = {Interest in reconstructing demographic histories has motivated the development of methods to estimate locus-specific pairwise coalescence times from whole-genome sequencing data. Here we introduce a powerful new method, ASMC, that can estimate coalescence times using only SNP array data, and is orders of magnitude faster than previous approaches. We applied ASMC to detect recent positive selection in 113,851 phased British samples from the UK Biobank, and detected 12 genome-wide significant signals, including 6 novel loci. We also applied ASMC to sequencing data from 498 Dutch individuals to detect background selection at deeper time scales. We detected strong heritability enrichment in regions of high background selection in an analysis of 20 independent diseases and complex traits using stratified linkage disequilibrium score regression, conditioned on a broad set of functional annotations (including other background selection annotations). These results underscore the widespread effects of background selection on the genetic architecture of complex traits.}, } @article {pmid30104756, year = {2018}, author = {Manning, P and van der Plas, F and Soliveres, S and Allan, E and Maestre, FT and Mace, G and Whittingham, MJ and Fischer, M}, title = {Publisher Correction: Redefining ecosystem multifunctionality.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1515}, doi = {10.1038/s41559-018-0660-x}, pmid = {30104756}, issn = {2397-334X}, abstract = {In the version of this Perspective originally published, in the figure in Box 3 the middle panel of the top row was incorrectly labelled '50% threshold-plus'; it should have read '50% threshold'. This has now been corrected.}, } @article {pmid30104755, year = {2018}, author = {}, title = {Robust regulations.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1333}, doi = {10.1038/s41559-018-0661-9}, pmid = {30104755}, issn = {2397-334X}, } @article {pmid30104754, year = {2018}, author = {Kukekova, AV and Johnson, JL and Xiang, X and Feng, S and Liu, S and Rando, HM and Kharlamova, AV and Herbeck, Y and Serdyukova, NA and Xiong, Z and Beklemischeva, V and Koepfli, KP and Gulevich, RG and Vladimirova, AV and Hekman, JP and Perelman, PL and Graphodatsky, AS and O'Brien, SJ and Wang, X and Clark, AG and Acland, GM and Trut, LN and Zhang, G}, title = {Author Correction: Red fox genome assembly identifies genomic regions associated with tame and aggressive behaviours.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1514}, doi = {10.1038/s41559-018-0664-6}, pmid = {30104754}, issn = {2397-334X}, abstract = {In the version of this Article originally published, there were some errors in the affiliations: Stephen J. O'Brien's affiliations were incorrectly listed as 8,9; they should have been 7,9. Affiliation 3 was incorrectly named the Institute of Cytology and Genetics of the Russian Academy of Sciences; it should have read Institute of Cytology and Genetics of the Siberian Branch of the Russian Academy of Sciences. Affiliation 4 was incorrectly named the Institute of Molecular and Cell Biology of the Russian Academy of Sciences; it should have read Institute of Molecular and Cellular Biology of the Siberian Branch of the Russian Academy of Sciences. These have now been corrected.}, } @article {pmid30104753, year = {2018}, author = {Britt, BB and Dalla Vecchia, FM and Chure, DJ and Engelmann, GF and Whiting, MF and Scheetz, RD}, title = {Caelestiventus hanseni gen. et sp. nov. extends the desert-dwelling pterosaur record back 65 million years.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1386-1392}, doi = {10.1038/s41559-018-0627-y}, pmid = {30104753}, issn = {2397-334X}, abstract = {Pterosaurs are the oldest known powered flying vertebrates. Originating in the Late Triassic, they thrived to the end of the Cretaceous. Triassic pterosaurs are extraordinarily rare and all but one specimen come from marine deposits in the Alps. A new comparatively large (wing span >150 cm) pterosaur, Caelestiventus hanseni gen. et sp. nov., from Upper Triassic desert deposits of western North America preserves delicate structural and pneumatic details not previously known in early pterosaurs, and allows a reinterpretation of crushed Triassic specimens. It shows that the earliest pterosaurs were geographically widely distributed and ecologically diverse, even living in harsh desert environments. It is the only record of desert-dwelling non-pterodactyloid pterosaurs and predates all known desert pterosaurs by more than 65 Myr. A phylogenetic analysis shows it is closely allied with Dimorphodon macronyx from the Early Jurassic of Britain.}, } @article {pmid30104752, year = {2018}, author = {Tsuboi, M and van der Bijl, W and Kopperud, BT and Erritzøe, J and Voje, KL and Kotrschal, A and Yopak, KE and Collin, SP and Iwaniuk, AN and Kolm, N}, title = {Breakdown of brain-body allometry and the encephalization of birds and mammals.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1492-1500}, doi = {10.1038/s41559-018-0632-1}, pmid = {30104752}, issn = {2397-334X}, abstract = {The allometric relationship between brain and body size among vertebrates is often considered a manifestation of evolutionary constraints. However, birds and mammals have undergone remarkable encephalization, in which brain size has increased without corresponding changes in body size. Here, we explore the hypothesis that a reduction of phenotypic integration between brain and body size has facilitated encephalization in birds and mammals. Using a large dataset comprising 20,213 specimens across 4,587 species of jawed vertebrates, we show that the among-species (evolutionary) brain-body allometries are remarkably constant, both across vertebrate classes and across taxonomic levels. Birds and mammals, however, are exceptional in that their within-species (static) allometries are shallower and more variable than in other vertebrates. These patterns are consistent with the idea that birds and mammals have reduced allometric constraints that are otherwise ubiquitous across jawed vertebrates. Further exploration of ontogenetic allometries in selected taxa of birds, fishes and mammals reveals that birds and mammals have extended the period of fetal brain growth compared to fishes. Based on these findings, we propose that avian and mammalian encephalization has been contingent on increased variability in brain growth patterns.}, } @article {pmid30104751, year = {2018}, author = {Johnson, DJ and Needham, J and Xu, C and Massoud, EC and Davies, SJ and Anderson-Teixeira, KJ and Bunyavejchewin, S and Chambers, JQ and Chang-Yang, CH and Chiang, JM and Chuyong, GB and Condit, R and Cordell, S and Fletcher, C and Giardina, CP and Giambelluca, TW and Gunatilleke, N and Gunatilleke, S and Hsieh, CF and Hubbell, S and Inman-Narahari, F and Kassim, AR and Katabuchi, M and Kenfack, D and Litton, CM and Lum, S and Mohamad, M and Nasardin, M and Ong, PS and Ostertag, R and Sack, L and Swenson, NG and Sun, IF and Tan, S and Thomas, DW and Thompson, J and Umaña, MN and Uriarte, M and Valencia, R and Yap, S and Zimmerman, J and McDowell, NG and McMahon, SM}, title = {Climate sensitive size-dependent survival in tropical trees.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1436-1442}, doi = {10.1038/s41559-018-0626-z}, pmid = {30104751}, issn = {2397-334X}, abstract = {Survival rates of large trees determine forest biomass dynamics. Survival rates of small trees have been linked to mechanisms that maintain biodiversity across tropical forests. How species survival rates change with size offers insight into the links between biodiversity and ecosystem function across tropical forests. We tested patterns of size-dependent tree survival across the tropics using data from 1,781 species and over 2 million individuals to assess whether tropical forests can be characterized by size-dependent life-history survival strategies. We found that species were classifiable into four 'survival modes' that explain life-history variation that shapes carbon cycling and the relative abundance within forests. Frequently collected functional traits, such as wood density, leaf mass per area and seed mass, were not generally predictive of the survival modes of species. Mean annual temperature and cumulative water deficit predicted the proportion of biomass of survival modes, indicating important links between evolutionary strategies, climate and carbon cycling. The application of survival modes in demographic simulations predicted biomass change across forest sites. Our results reveal globally identifiable size-dependent survival strategies that differ across diverse systems in a consistent way. The abundance of survival modes and interaction with climate ultimately determine forest structure, carbon storage in biomass and future forest trajectories.}, } @article {pmid30104750, year = {2018}, author = {Tian, F and Wigneron, JP and Ciais, P and Chave, J and Ogée, J and Peñuelas, J and Ræbild, A and Domec, JC and Tong, X and Brandt, M and Mialon, A and Rodriguez-Fernandez, N and Tagesson, T and Al-Yaari, A and Kerr, Y and Chen, C and Myneni, RB and Zhang, W and Ardö, J and Fensholt, R}, title = {Coupling of ecosystem-scale plant water storage and leaf phenology observed by satellite.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1428-1435}, doi = {10.1038/s41559-018-0630-3}, pmid = {30104750}, issn = {2397-334X}, abstract = {Plant water storage is fundamental to the functioning of terrestrial ecosystems by participating in plant metabolism, nutrient and sugar transport, and maintenance of the integrity of the hydraulic system of the plant. However, a global view of the size and dynamics of the water pools stored in plant tissues is still lacking. Here, we report global patterns of seasonal variations in ecosystem-scale plant water storage and their relationship with leaf phenology, based on space-borne measurements of L-band vegetation optical depth. We find that seasonal variations in plant water storage are highly synchronous with leaf phenology for the boreal and temperate forests, but asynchronous for the tropical woodlands, where the seasonal development of plant water storage lags behind leaf area by up to 180 days. Contrasting patterns of the time lag between plant water storage and terrestrial groundwater storage are also evident in these ecosystems. A comparison of the water cycle components in seasonally dry tropical woodlands highlights the buffering effect of plant water storage on the seasonal dynamics of water supply and demand. Our results offer insights into ecosystem-scale plant water relations globally and provide a basis for an improved parameterization of eco-hydrological and Earth system models.}, } @article {pmid30104749, year = {2018}, author = {Galaz, V and Crona, B and Dauriach, A and Jouffray, JB and Österblom, H and Fichtner, J}, title = {Tax havens and global environmental degradation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1352-1357}, doi = {10.1038/s41559-018-0497-3}, pmid = {30104749}, issn = {2397-334X}, abstract = {The release of classified documents in the past years have offered a rare glimpse into the opaque world of tax havens and their role in the global economy. Although the political, economic and social implications related to these financial secrecy jurisdictions are known, their role in supporting economic activities with potentially detrimental environmental consequences have until now been largely ignored. Here, we combine quantitative analysis with case descriptions to elaborate and quantify the connections between tax havens and the environment, both in global fisheries and the Brazilian Amazon. We show that while only 4% of all registered fishing vessels are currently flagged in a tax haven, 70% of the known vessels implicated in illegal, unreported and unregulated fishing are, or have been, flagged under a tax haven jurisdiction. We also find that between October 2000 and August 2011, 68% of all investigated foreign capital to nine focal companies in the soy and beef sectors in the Brazilian Amazon was transferred through one, or several, known tax havens. This represents as much as 90-100% of foreign capital for some companies investigated. We highlight key research challenges for the academic community that emerge from our findings and present a set of proposed actions for policy that would put tax havens on the global sustainability agenda.}, } @article {pmid30104690, year = {2018}, author = {Nobrega, FL and Vlot, M and de Jonge, PA and Dreesens, LL and Beaumont, HJE and Lavigne, R and Dutilh, BE and Brouns, SJJ}, title = {Targeting mechanisms of tailed bacteriophages.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {12}, pages = {760-773}, doi = {10.1038/s41579-018-0070-8}, pmid = {30104690}, issn = {1740-1534}, abstract = {Phages differ substantially in the bacterial hosts that they infect. Their host range is determined by the specific structures that they use to target bacterial cells. Tailed phages use a broad range of receptor-binding proteins, such as tail fibres, tail spikes and the central tail spike, to target their cognate bacterial cell surface receptors. Recent technical advances and new structure-function insights have begun to unravel the molecular mechanisms and temporal dynamics that govern these interactions. Here, we review the current understanding of the targeting machinery and mechanisms of tailed phages. These new insights and approaches pave the way for the application of phages in medicine and biotechnology and enable deeper understanding of their ecology and evolution.}, } @article {pmid30104596, year = {2018}, author = {, }, title = {Probing high-momentum protons and neutrons in neutron-rich nuclei.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {617-621}, doi = {10.1038/s41586-018-0400-z}, pmid = {30104596}, issn = {1476-4687}, abstract = {The atomic nucleus is one of the densest and most complex quantum-mechanical systems in nature. Nuclei account for nearly all the mass of the visible Universe. The properties of individual nucleons (protons and neutrons) in nuclei can be probed by scattering a high-energy particle from the nucleus and detecting this particle after it scatters, often also detecting an additional knocked-out proton. Analysis of electron- and proton-scattering experiments suggests that some nucleons in nuclei form close-proximity neutron-proton pairs1-12 with high nucleon momentum, greater than the nuclear Fermi momentum. However, how excess neutrons in neutron-rich nuclei form such close-proximity pairs remains unclear. Here we measure protons and, for the first time, neutrons knocked out of medium-to-heavy nuclei by high-energy electrons and show that the fraction of high-momentum protons increases markedly with the neutron excess in the nucleus, whereas the fraction of high-momentum neutrons decreases slightly. This effect is surprising because in the classical nuclear shell model, protons and neutrons obey Fermi statistics, have little correlation and mostly fill independent energy shells. These high-momentum nucleons in neutron-rich nuclei are important for understanding nuclear parton distribution functions (the partial momentum distribution of the constituents of the nucleon) and changes in the quark distributions of nucleons bound in nuclei (the EMC effect)1,13,14. They are also relevant for the interpretation of neutrino-oscillation measurements15 and understanding of neutron-rich systems such as neutron stars3,16.}, } @article {pmid30104594, year = {2018}, author = {Gewin, V}, title = {Top tips for building and maintaining international collaborations.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {401-402}, doi = {10.1038/d41586-018-05944-x}, pmid = {30104594}, issn = {1476-4687}, } @article {pmid30104593, year = {2018}, author = {Margócsy, D and Somos, M and Joffe, SN}, title = {Sex, religion and a towering treatise on anatomy.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {304-305}, doi = {10.1038/d41586-018-05941-0}, pmid = {30104593}, issn = {1476-4687}, } @article {pmid30104592, year = {2018}, author = {}, title = {The spectre of smallpox lingers.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {281}, doi = {10.1038/d41586-018-05936-x}, pmid = {30104592}, issn = {1476-4687}, } @article {pmid30104590, year = {2018}, author = {Mewes, M}, title = {Special relativity validated by neutrinos.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {316-317}, doi = {10.1038/d41586-018-05931-2}, pmid = {30104590}, issn = {1476-4687}, } @article {pmid30104582, year = {2018}, author = {Coyne, CB}, title = {STING'ing Zika virus in neurons.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {975-976}, doi = {10.1038/s41564-018-0232-5}, pmid = {30104582}, issn = {2058-5276}, } @article {pmid30104439, year = {2018}, author = {Madden, JR and Langley, EJG and Whiteside, MA and Beardsworth, CE and van Horik, JO}, title = {The quick are the dead: pheasants that are slow to reverse a learned association survive for longer in the wild.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104439}, issn = {1471-2970}, abstract = {Cognitive abilities probably evolve through natural selection if they provide individuals with fitness benefits. A growing number of studies demonstrate a positive relationship between performance in psychometric tasks and (proxy) measures of fitness. We assayed the performance of 154 common pheasant (Phasianus colchicus) chicks on tests of acquisition and reversal learning, using a different set of chicks and different set of cue types (spatial location and colour) in each of two years and then followed their fates after release into the wild. Across all birds, individuals that were slow to reverse previously learned associations were more likely to survive to four months old. For heavy birds, individuals that rapidly acquired an association had improved survival to four months, whereas for light birds, slow acquirers were more likely to be alive. Slow reversers also exhibited less exploratory behaviour in assays when five weeks old. Fast acquirers visited more artificial feeders after release. In contrast to most other studies, we showed that apparently 'poor' cognitive performance (slow reversal speed suggesting low behavioural flexibility) correlates with fitness benefits in at least some circumstances. This correlation suggests a novel mechanism by which continued exaggeration of cognitive abilities may be constrained.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104438, year = {2018}, author = {Huebner, F and Fichtel, C and Kappeler, PM}, title = {Linking cognition with fitness in a wild primate: fitness correlates of problem-solving performance and spatial learning ability.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104438}, issn = {1471-2970}, abstract = {Linking the cognitive performance of wild animals with fitness consequences is crucial for understanding evolutionary processes that shape individual variation in cognition. However, the few studies that have examined these links revealed differing relationships between various cognitive performance measures and fitness proxies. To contribute additional comparative data to this body of research, we linked individual performance during repeated problem-solving and spatial learning ability in a maze with body condition and survival in wild grey mouse lemurs (Microcebus murinus). All four variables exhibited substantial inter-individual variation. Solving efficiency in the problem-solving task, but not spatial learning performance, predicted the magnitude of change in body condition after the harsh dry season, indicating that the ability to quickly apply a newly discovered motor technique might also facilitate exploitation of new, natural food resources. Survival was not linked with performance in both tasks, however, suggesting that mouse lemurs' survival might not depend on the cognitive performances addressed here. Our study is the first linking cognition with fitness proxies in a wild primate species, and our discussion highlights the importance and challenges of accounting for a species' life history and ecology in choosing meaningful cognitive and fitness variables for a study in the wild.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104437, year = {2018}, author = {Wascher, CAF and Kulahci, IG and Langley, EJG and Shaw, RC}, title = {How does cognition shape social relationships?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104437}, issn = {1471-2970}, abstract = {The requirements of living in social groups, and forming and maintaining social relationships are hypothesized to be one of the major drivers behind the evolution of cognitive abilities. Most empirical studies investigating the relationships between sociality and cognition compare cognitive performance between species living in systems that differ in social complexity. In this review, we ask whether and how individuals benefit from cognitive skills in their social interactions. Cognitive abilities, such as perception, attention, learning, memory, and inhibitory control, aid in forming and maintaining social relationships. We investigate whether there is evidence that individual variation in these abilities influences individual variation in social relationships. We then consider the evolutionary consequences of the interaction between sociality and cognitive ability to address whether bi-directional relationships exist between the two, such that cognition can both shape and be shaped by social interactions and the social environment. In doing so, we suggest that social network analysis is emerging as a powerful tool that can be used to test for directional causal relationships between sociality and cognition. Overall, our review highlights the importance of investigating individual variation in cognition to understand how it shapes the patterns of social relationships.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104436, year = {2018}, author = {Dalesman, S}, title = {Habitat and social context affect memory phenotype, exploration and covariance among these traits.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104436}, issn = {1471-2970}, abstract = {Individual differences in cognitive ability are predicted to covary with other behavioural traits such as exploration and boldness. Selection within different habitats may act to either enhance or break down covariance among traits; alternatively, changing the environmental context in which traits are assessed may result in plasticity that alters trait covariance. Pond snails, Lymnaea stagnalis, from two laboratory strains (more than 20 generations in captivity) and F1 laboratory reared from six wild populations were tested for long-term memory and exploration traits (speed and thigmotaxis) following maintenance in grouped and isolated conditions to determine if isolation: (i) alters memory and exploration; and (ii) alters covariance between memory and exploration. Populations that demonstrated strong memory formation (longer duration) under grouped conditions demonstrated weaker memory formation and reduced both speed and thigmotaxis following isolation. In wild populations, snails showed no relationship between memory and exploration in grouped conditions; however, following isolation, exploration behaviour was negatively correlated with memory, i.e. slow-explorers showing low levels of thigmotaxis formed stronger memories. Laboratory strains demonstrated no covariance among exploration traits and memory independent of context. Together these data demonstrate that the relationship between cognition and exploration traits can depend on both habitat and context-specific trait plasticity.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104435, year = {2018}, author = {Boogert, NJ and Lachlan, RF and Spencer, KA and Templeton, CN and Farine, DR}, title = {Stress hormones, social associations and song learning in zebra finches.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104435}, issn = {1471-2970}, abstract = {The use of information provided by others is a common short-cut adopted to inform decision-making. However, instead of indiscriminately copying others, animals are often selective in what, when and whom they copy. How do they decide which 'social learning strategy' to use? Previous research indicates that stress hormone exposure in early life may be important: while juvenile zebra finches copied their parents' behaviour when solving novel foraging tasks, those exposed to elevated levels of corticosterone (CORT) during development copied only unrelated adults. Here, we tested whether this switch in social learning strategy generalizes to vocal learning. In zebra finches, juvenile males often copy their father's song; would CORT-treated juveniles in free-flying aviaries switch to copying songs of other males? We found that CORT-treated juveniles copied their father's song less accurately as compared to control juveniles. We hypothesized that this could be due to having weaker social foraging associations with their fathers, and found that sons that spent less time foraging with their fathers produced less similar songs. Our findings are in line with a novel hypothesis linking early-life stress and social learning: early-life CORT exposure may affect social learning indirectly as a result of the way it shapes social affiliations.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104434, year = {2018}, author = {Sauce, B and Bendrath, S and Herzfeld, M and Siegel, D and Style, C and Rab, S and Korabelnikov, J and Matzel, LD}, title = {The impact of environmental interventions among mouse siblings on the heritability and malleability of general cognitive ability.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104434}, issn = {1471-2970}, abstract = {General cognitive ability can be highly heritable in some species, but at the same time, is very malleable. This apparent paradox could potentially be explained by gene-environment interactions and correlations that remain hidden due to experimental limitations on human research and blind spots in animal research. Here, we shed light on this issue by combining the design of a sibling study with an environmental intervention administered to laboratory mice. The analysis included 58 litters of four full-sibling genetically heterogeneous CD-1 male mice, for a total of 232 mice. We separated the mice into two subsets of siblings: a control group (maintained in standard laboratory conditions) and an environmental-enrichment group (which had access to continuous physical exercise and daily exposure to novel environments). We found that general cognitive ability in mice has substantial heritability (24% for all mice) and is also malleable. The mice that experienced the enriched environment had a mean intelligence score that was 0.44 standard deviations higher than their siblings in the control group (equivalent to gains of 6.6 IQ points in humans). We also found that the estimate of heritability changed between groups (55% in the control group compared with non-significant 15% in the enrichment group), analogous to findings in humans across socio-economic status. Unexpectedly, no evidence of gene-environment interaction was detected, and so the change in heritability might be best explained by higher environmental variance in the enrichment group. Our findings, as well as the 'sibling intervention procedure' for mice, may be valuable to future research on the heritability, mechanisms and evolution of cognition.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104433, year = {2018}, author = {Ashton, BJ and Thornton, A and Ridley, AR}, title = {An intraspecific appraisal of the social intelligence hypothesis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104433}, issn = {1471-2970}, support = {BB/H021817/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The prevailing hypotheses for the evolution of cognition focus on either the demands associated with group living (the social intelligence hypothesis (SIH)) or ecological challenges such as finding food. Comparative studies testing these hypotheses have generated highly conflicting results; consequently, our understanding of the drivers of cognitive evolution remains limited. To understand how selection shapes cognition, research must incorporate an intraspecific approach, focusing on the causes and consequences of individual variation in cognition. Here, we review the findings of recent intraspecific cognitive research to investigate the predictions of the SIH. Extensive evidence from our own research on Australian magpies (Cracticus tibicen dorsalis), and a number of other taxa, suggests that individuals in larger social groups exhibit elevated cognitive performance and, in some cases, elevated reproductive fitness. Not only do these findings demonstrate how the social environment has the potential to shape cognitive evolution, but crucially, they demonstrate the importance of considering both genetic and developmental factors when attempting to explain the causes of cognitive variation.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104432, year = {2018}, author = {Pike, TW and Ramsey, M and Wilkinson, A}, title = {Environmentally induced changes to brain morphology predict cognitive performance.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104432}, issn = {1471-2970}, abstract = {The relationship between the size and structure of a species' brain and its cognitive capacity has long interested scientists. Generally, this work relates interspecific variation in brain anatomy with performance on a variety of cognitive tasks. However, brains are known to show considerable short-term plasticity in response to a range of social, ecological and environmental factors. Despite this, we have a remarkably poor understanding of how this impacts on an animal's cognitive performance. Here, we non-invasively manipulated the relative size of brain regions associated with processing visual and chemical information in fish (the optic tectum and olfactory bulbs, respectively). We then tested performance in a cognitive task in which information from the two sensory modalities was in conflict. Although the fish could effectively use both visual and chemical information if presented in isolation, when they received cues from both modalities simultaneously, those with a relatively better developed optic tectum showed a greater reliance on visual information, while individuals with relatively better developed olfactory bulbs showed a greater reliance on chemical information. These results suggest that short-term changes in brain structure, possibly resulting from an attempt to minimize the costs of developing unnecessary but energetically expensive brain regions, may have marked effects on cognitive performance.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104431, year = {2018}, author = {Davidson, GL and Cooke, AC and Johnson, CN and Quinn, JL}, title = {The gut microbiome as a driver of individual variation in cognition and functional behaviour.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104431}, issn = {1471-2970}, abstract = {Research into proximate and ultimate mechanisms of individual cognitive variation in animal populations is a rapidly growing field that incorporates physiological, behavioural and evolutionary investigations. Recent studies in humans and laboratory animals have shown that the enteric microbial community plays a central role in brain function and development. The 'gut-brain axis' represents a multi-directional signalling system that encompasses neurological, immunological and hormonal pathways. In particular it is tightly linked with the hypothalamic-pituitary-adrenal axis (HPA), a system that regulates stress hormone release and influences brain development and function. Experimental examination of the microbiome through manipulation of diet, infection, stress and exercise, suggests direct effects on cognition, including learning and memory. However, our understanding of these processes in natural populations is extremely limited. Here, we outline how recent advances in predominantly laboratory-based microbiome research can be applied to understanding individual differences in cognition. Experimental manipulation of the microbiome across natal and adult environments will help to unravel the interplay between cognitive variation and the gut microbial community. Focus on individual variation in the gut microbiome and cognition in natural populations will reveal new insight into the environmental and evolutionary constraints that drive individual cognitive variation.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104430, year = {2018}, author = {Sorato, E and Zidar, J and Garnham, L and Wilson, A and Løvlie, H}, title = {Heritabilities and co-variation among cognitive traits in red junglefowl.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104430}, issn = {1471-2970}, abstract = {Natural selection can act on between-individual variation in cognitive abilities, yet evolutionary responses depend on the presence of underlying genetic variation. It is, therefore, crucial to determine the relative extent of genetic versus environmental control of these among-individual differences in cognitive traits to understand their causes and evolutionary potential. We investigated heritability of associative learning performance and of a cognitive judgement bias (optimism), as well as their covariation, in a captive pedigree-bred population of red junglefowl (Gallus gallus, n > 300 chicks over 5 years). We analysed performance in discriminative and reversal learning (two facets of associative learning), and cognitive judgement bias, by conducting animal models to disentangle genetic from environmental contributions. We demonstrate moderate heritability for reversal learning, and weak to no heritability for optimism and discriminative learning, respectively. The two facets of associative learning were weakly negatively correlated, consistent with hypothesized trade-offs underpinning individual cognitive styles. Reversal, but not discriminative learning performance, was associated with judgement bias; less optimistic individuals reversed a previously learnt association faster. Together these results indicate that genetic and environmental contributions differ among traits. While modular models of cognitive abilities predict a lack of common genetic control for different cognitive traits, further investigation is required to fully ascertain the degree of covariation between a broader range of cognitive traits and the extent of any shared genetic control.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104429, year = {2018}, author = {Dubois, J and Galdi, P and Paul, LK and Adolphs, R}, title = {A distributed brain network predicts general intelligence from resting-state human neuroimaging data.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104429}, issn = {1471-2970}, support = {P50 MH094258/MH/NIMH NIH HHS/United States ; U01 NS103780/NS/NINDS NIH HHS/United States ; }, abstract = {Individual people differ in their ability to reason, solve problems, think abstractly, plan and learn. A reliable measure of this general ability, also known as intelligence, can be derived from scores across a diverse set of cognitive tasks. There is great interest in understanding the neural underpinnings of individual differences in intelligence, because it is the single best predictor of long-term life success. The most replicated neural correlate of human intelligence to date is total brain volume; however, this coarse morphometric correlate says little about function. Here, we ask whether measurements of the activity of the resting brain (resting-state fMRI) might also carry information about intelligence. We used the final release of the Young Adult Human Connectome Project (N = 884 subjects after exclusions), providing a full hour of resting-state fMRI per subject; controlled for gender, age and brain volume; and derived a reliable estimate of general intelligence from scores on multiple cognitive tasks. Using a cross-validated predictive framework, we predicted 20% of the variance in general intelligence in the sampled population from their resting-state connectivity matrices. Interestingly, no single anatomical structure or network was responsible or necessary for this prediction, which instead relied on redundant information distributed across the brain.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104428, year = {2018}, author = {Völter, CJ and Tinklenberg, B and Call, J and Seed, AM}, title = {Comparative psychometrics: establishing what differs is central to understanding what evolves.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104428}, issn = {1471-2970}, abstract = {Cognitive abilities cannot be measured directly. What we can measure is individual variation in task performance. In this paper, we first make the case for why we should be interested in mapping individual differences in task performance onto particular cognitive abilities: we suggest that it is crucial for examining the causes and consequences of variation both within and between species. As a case study, we examine whether multiple measures of inhibitory control for non-human animals do indeed produce correlated task performance; however, no clear pattern emerges that would support the notion of a common cognitive ability underpinning individual differences in performance. We advocate a psychometric approach involving a three-step programme to make theoretical and empirical progress: first, we need tasks that reveal signature limits in performance. Second, we need to assess the reliability of individual differences in task performance. Third, multi-trait multi-method test batteries will be instrumental in validating cognitive abilities. Together, these steps will help us to establish what varies between individuals that could impact their fitness and ultimately shape the course of the evolution of animal minds. Finally, we propose executive functions, including working memory, inhibitory control and attentional shifting, as a sensible starting point for this endeavour.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104427, year = {2018}, author = {Dougherty, LR and Guillette, LM}, title = {Linking personality and cognition: a meta-analysis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104427}, issn = {1471-2970}, abstract = {In the past decade, several conceptual papers have linked variation in animal personality to variation in cognition, and recent years have seen a flood of empirical studies testing this link. However, these results have not been synthesized in a quantitative way. Here, we systematically search the literature and conduct a phylogenetically controlled meta-analysis of empirical papers that have tested the relationship between animal personality (exploration, boldness, activity, aggression and sociability) and cognition (initial learning/reversal speed, number of correct choices/errors after standard training). We find evidence for a small but significant relationship between variation in personality and variation in learning across species in the absolute scale; however, the direction of this relationship is highly variable and when both positive and negative effect sizes are considered, the average effect size does not differ significantly from zero. Importantly, this variation among studies is not explained by differences in personality or learning measure, or taxonomic grouping. Further, these results do not support current hypotheses suggesting that that fast-explorers are fast-learners or that slow-explorers perform better on tests of reversal learning. Rather, we find evidence that bold animals are faster learners, but only when boldness is measured in response to a predator (or simulated predator) and not when boldness is measured by exposure to a novel object (or novel food). Further, although only a small sub-sample of papers reported results separately for males and females, sex explained a significant amount of variation in effect size. These results, therefore, suggest that, while personality and learning are indeed related across a range of species, the direction of this relationship is highly variable. Thus further empirical work is needed to determine whether there are important moderators of this relationship.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104426, year = {2018}, author = {Cauchoix, M and Chow, PKY and van Horik, JO and Atance, CM and Barbeau, EJ and Barragan-Jason, G and Bize, P and Boussard, A and Buechel, SD and Cabirol, A and Cauchard, L and Claidière, N and Dalesman, S and Devaud, JM and Didic, M and Doligez, B and Fagot, J and Fichtel, C and Henke-von der Malsburg, J and Hermer, E and Huber, L and Huebner, F and Kappeler, PM and Klein, S and Langbein, J and Langley, EJG and Lea, SEG and Lihoreau, M and Lovlie, H and Matzel, LD and Nakagawa, S and Nawroth, C and Oesterwind, S and Sauce, B and Smith, EA and Sorato, E and Tebbich, S and Wallis, LJ and Whiteside, MA and Wilkinson, A and Chaine, AS and Morand-Ferron, J}, title = {The repeatability of cognitive performance: a meta-analysis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104426}, issn = {1471-2970}, abstract = {Behavioural and cognitive processes play important roles in mediating an individual's interactions with its environment. Yet, while there is a vast literature on repeatable individual differences in behaviour, relatively little is known about the repeatability of cognitive performance. To further our understanding of the evolution of cognition, we gathered 44 studies on individual performance of 25 species across six animal classes and used meta-analysis to assess whether cognitive performance is repeatable. We compared repeatability (R) in performance (1) on the same task presented at different times (temporal repeatability), and (2) on different tasks that measured the same putative cognitive ability (contextual repeatability). We also addressed whether R estimates were influenced by seven extrinsic factors (moderators): type of cognitive performance measurement, type of cognitive task, delay between tests, origin of the subjects, experimental context, taxonomic class and publication status. We found support for both temporal and contextual repeatability of cognitive performance, with mean R estimates ranging between 0.15 and 0.28. Repeatability estimates were mostly influenced by the type of cognitive performance measures and publication status. Our findings highlight the widespread occurrence of consistent inter-individual variation in cognition across a range of taxa which, like behaviour, may be associated with fitness outcomes.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104425, year = {2018}, author = {Boogert, NJ and Madden, JR and Morand-Ferron, J and Thornton, A}, title = {Measuring and understanding individual differences in cognition.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1756}, pages = {}, pmid = {30104425}, issn = {1471-2970}, abstract = {Individuals vary in their cognitive performance. While this variation forms the foundation of the study of human psychometrics, its broader importance is only recently being recognized. Explicitly acknowledging this individual variation found in both humans and non-human animals provides a novel opportunity to understand the mechanisms, development and evolution of cognition. The papers in this special issue highlight the growing emphasis on individual cognitive differences from fields as diverse as neurobiology, experimental psychology and evolutionary biology. Here, we synthesize this body of work. We consider the distinct challenges in quantifying individual differences in cognition and provide concrete methodological recommendations. In particular, future studies would benefit from using multiple task variants to ensure they target specific, clearly defined cognitive traits and from conducting repeated testing to assess individual consistency. We then consider how neural, genetic, developmental and behavioural factors may generate individual differences in cognition. Finally, we discuss the potential fitness consequences of individual cognitive variation and place these into an evolutionary framework with testable hypotheses. We intend for this special issue to stimulate researchers to position individual variation at the centre of the cognitive sciences.This article is part of the theme issue 'Causes and consequences of individual differences in cognitive abilities'.}, } @article {pmid30104389, year = {2018}, author = {Ujisawa, T and Ohta, A and Ii, T and Minakuchi, Y and Toyoda, A and Ii, M and Kuhara, A}, title = {Endoribonuclease ENDU-2 regulates multiple traits including cold tolerance via cell autonomous and nonautonomous controls in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8823-8828}, pmid = {30104389}, issn = {1091-6490}, mesh = {Acclimatization/*physiology ; Animals ; Caenorhabditis elegans/*enzymology/genetics ; Caenorhabditis elegans Proteins/biosynthesis/genetics ; Caspases/biosynthesis/genetics ; Endoribonucleases/genetics/*metabolism ; Gene Expression Profiling ; *Quantitative Trait, Heritable ; Signal Transduction/*physiology ; Synapses/genetics/*metabolism ; TRPC Cation Channels/genetics/metabolism ; }, abstract = {Environmental temperature acclimation is essential to animal survival, yet thermoregulation mechanisms remain poorly understood. We demonstrate cold tolerance in Caenorhabditis elegans as regulated by paired ADL chemosensory neurons via Ca2+-dependent endoribonuclease (EndoU) ENDU-2. Loss of ENDU-2 function results in life span, brood size, and synaptic remodeling abnormalities in addition to enhanced cold tolerance. Enzymatic ENDU-2 defects localized in the ADL and certain muscle cells led to increased cold tolerance in endu-2 mutants. Ca2+ imaging revealed ADL neurons were responsive to temperature stimuli through transient receptor potential (TRP) channels, concluding that ADL function requires ENDU-2 action in both cell-autonomous and cell-nonautonomous mechanisms. ENDU-2 is involved in caspase expression, which is central to cold tolerance and synaptic remodeling in dorsal nerve cord. We therefore conclude that ENDU-2 regulates cell type-dependent, cell-autonomous, and cell-nonautonomous cold tolerance.}, } @article {pmid30104388, year = {2018}, author = {Culp, TE and Shen, YX and Geitner, M and Paul, M and Roy, A and Behr, MJ and Rosenberg, S and Gu, J and Kumar, M and Gomez, ED}, title = {Electron tomography reveals details of the internal microstructure of desalination membranes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8694-8699}, pmid = {30104388}, issn = {1091-6490}, abstract = {As water availability becomes a growing challenge in various regions throughout the world, desalination and wastewater reclamation through technologies such as reverse osmosis (RO) are becoming more important. Nevertheless, many open questions remain regarding the internal structure of thin-film composite RO membranes. In this work, fully aromatic polyamide films that serve as the active layer of state-of-the-art water filtration membranes were investigated using high-angle annular dark-field scanning transmission electron microscopy tomography. Reconstructions of the 3D morphology reveal intricate aspects of the complex microstructure not visible from 2D projections. We find that internal voids of the active layer of compressed commercial membranes account for less than 0.2% of the total polymer volume, contrary to previously reported values that are two orders of magnitude higher. Measurements of the local variation in polyamide density from electron tomography reveal that the polymer density is highest at the permeable surface for the two membranes tested and establish the significance of surface area on RO membrane transport properties. The same type of analyses could provide explanations for different flux variations with surface area for other types of membranes where the density is distributed differently. Thus, 3D reconstructions and quantitative analyses will be crucial to characterize the complex morphology of polymeric membranes used in next-generation water-purification membranes.}, } @article {pmid30104387, year = {2018}, author = {Anderson, RL and Trivedi, DV and Sarkar, SS and Henze, M and Ma, W and Gong, H and Rogers, CS and Gorham, JM and Wong, FL and Morck, MM and Seidman, JG and Ruppel, KM and Irving, TC and Cooke, R and Green, EM and Spudich, JA}, title = {Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8143-E8152}, pmid = {30104387}, issn = {1091-6490}, support = {P41 GM103622/GM/NIGMS NIH HHS/United States ; R01 GM033289/GM/NIGMS NIH HHS/United States ; R01 HL117138/HL/NHLBI NIH HHS/United States ; R01 HL084553/HL/NHLBI NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; R01 AR062279/AR/NIAMS NIH HHS/United States ; S10 RR026780/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Benzylamines/*chemistry/pharmacology ; Cardiomegaly/enzymology/genetics ; Humans ; Muscle, Skeletal/enzymology ; Mutation ; Swine ; Swine, Miniature ; Uracil/*analogs & derivatives/chemistry/pharmacology ; Ventricular Myosins/*chemistry/genetics/metabolism ; }, abstract = {Mutations in β-cardiac myosin, the predominant motor protein for human heart contraction, can alter power output and cause cardiomyopathy. However, measurements of the intrinsic force, velocity, and ATPase activity of myosin have not provided a consistent mechanism to link mutations to muscle pathology. An alternative model posits that mutations in myosin affect the stability of a sequestered, super relaxed state (SRX) of the protein with very slow ATP hydrolysis and thereby change the number of myosin heads accessible to actin. Here we show that purified human β-cardiac myosin exists partly in an SRX and may in part correspond to a folded-back conformation of myosin heads observed in muscle fibers around the thick filament backbone. Mutations that cause hypertrophic cardiomyopathy destabilize this state, while the small molecule mavacamten promotes it. These findings provide a biochemical and structural link between the genetics and physiology of cardiomyopathy with implications for therapeutic strategies.}, } @article {pmid30104386, year = {2018}, author = {Wang, Q and Rio, DC}, title = {JUM is a computational method for comprehensive annotation-free analysis of alternative pre-mRNA splicing patterns.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8181-E8190}, pmid = {30104386}, issn = {1091-6490}, support = {P50 GM102706/GM/NIGMS NIH HHS/United States ; R01 GM097352/GM/NIGMS NIH HHS/United States ; R35 GM118121/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Computer Simulation ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster ; Humans ; K562 Cells ; *Models, Genetic ; *Molecular Sequence Annotation ; Mutation ; Neoplasm Proteins/genetics/metabolism ; *Neoplasms/genetics/metabolism ; *RNA Precursors/genetics/metabolism ; *RNA Splicing ; RNA Splicing Factors/genetics/metabolism ; *RNA, Neoplasm/genetics/metabolism ; }, abstract = {Alternative pre-mRNA splicing (AS) greatly diversifies metazoan transcriptomes and proteomes and is crucial for gene regulation. Current computational analysis methods of AS from Illumina RNA-sequencing data rely on preannotated libraries of known spliced transcripts, which hinders AS analysis with poorly annotated genomes and can further mask unknown AS patterns. To address this critical bioinformatics problem, we developed a method called the junction usage model (JUM) that uses a bottom-up approach to identify, analyze, and quantitate global AS profiles without any prior transcriptome annotations. JUM accurately reports global AS changes in terms of the five conventional AS patterns and an additional "composite" category composed of inseparable combinations of conventional patterns. JUM stringently classifies the difficult and disease-relevant pattern of intron retention (IR), reducing the false positive rate of IR detection commonly seen in other annotation-based methods to near-negligible rates. When analyzing AS in RNA samples derived from Drosophila heads, human tumors, and human cell lines bearing cancer-associated splicing factor mutations, JUM consistently identified approximately twice the number of novel AS events missed by other methods. Computational simulations showed JUM exhibits a 1.2 to 4.8 times higher true positive rate at a fixed cutoff of 5% false discovery rate. In summary, JUM provides a framework and improved method that removes the necessity for transcriptome annotations and enables the detection, analysis, and quantification of AS patterns in complex metazoan transcriptomes with superior accuracy.}, } @article {pmid30104385, year = {2018}, author = {Chen, SY and Ho, CT and Liu, WW and Lucanic, M and Shih, HM and Huang, PH and Cheng, HJ}, title = {Regulation of axon repulsion by MAX-1 SUMOylation and AP-3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8236-E8245}, pmid = {30104385}, issn = {1091-6490}, mesh = {Animals ; Axons/*metabolism ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; Protein Transport/physiology ; Sumoylation/*physiology ; Transcription Factors/genetics/*metabolism ; }, abstract = {During neural development, growing axons express specific surface receptors in response to various environmental guidance cues. These axon guidance receptors are regulated through intracellular trafficking and degradation to enable navigating axons to reach their targets. In Caenorhabditis elegans, the UNC-5 receptor is necessary for dorsal migration of developing motor axons. We previously found that MAX-1 is required for UNC-5-mediated axon repulsion, but its mechanism of action remained unclear. Here, we demonstrate that UNC-5-mediated axon repulsion in C. elegans motor axons requires both max-1 SUMOylation and the AP-3 complex β subunit gene, apb-3 Genetic interaction studies show that max-1 is SUMOylated by gei-17/PIAS1 and acts upstream of apb-3 Biochemical analysis suggests that constitutive interaction of MAX-1 and UNC-5 receptor is weakened by MAX-1 SUMOylation and by the presence of APB-3, a competitive interactor with UNC-5. Overexpression of APB-3 reroutes the trafficking of UNC-5 receptor into the lysosome for protein degradation. In vivo fluorescence recovery after photobleaching experiments shows that MAX-1 SUMOylation and APB-3 are required for proper trafficking of UNC-5 receptor in the axon. Our results demonstrate that SUMOylation of MAX-1 plays an important role in regulating AP-3-mediated trafficking and degradation of UNC-5 receptors during axon guidance.}, } @article {pmid30104384, year = {2018}, author = {Li, Y and Li, C and Li, S and Peng, Q and An, NA and He, A and Li, CY}, title = {Human exonization through differential nucleosome occupancy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8817-8822}, pmid = {30104384}, issn = {1091-6490}, mesh = {Animals ; Base Composition/*physiology ; *Evolution, Molecular ; Exons/*physiology ; Genome-Wide Association Study ; Humans ; Introns/*physiology ; Macaca ; Mice ; Nucleosomes/genetics/*metabolism ; }, abstract = {Nucleosomal modifications have been implicated in fundamental epigenetic regulation, but the roles of nucleosome occupancy in shaping changes through evolution remain to be addressed. Here we present high-resolution nucleosome occupancy profiles for multiple tissues derived from human, macaque, tree shrew, mouse, and pig. Genome-wide comparison reveals conserved nucleosome occupancy profiles across both different species and tissue types. Notably, we found significantly higher levels of nucleosome occupancy in exons than in introns, a pattern correlated with the different exon-intron GC content. We then determined whether this biased occupancy may play roles in the origination of new exons through evolution, rather than being a downstream effect of exonization, through a comparative approach to sequentially trace the order of the exonization and biased nucleosome binding. By identifying recently evolved exons in human but not in macaque using matched RNA sequencing, we found that higher exonic nucleosome occupancy also existed in macaque regions orthologous to these exons. Presumably, such biased nucleosome occupancy facilitates the origination of new exons by increasing the splice strength of the ancestral nonexonic regions through driving a local difference in GC content. These data thus support a model that sites bound by nucleosomes are more likely to evolve into exons, which we term the "nucleosome-first" model.}, } @article {pmid30104383, year = {2018}, author = {Chen, M and Lin, JY and Hur, J and Pelletier, JM and Baden, R and Pellegrini, M and Harada, JJ and Goldberg, RB}, title = {Seed genome hypomethylated regions are enriched in transcription factor genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8315-E8322}, pmid = {30104383}, issn = {1091-6490}, mesh = {*Arabidopsis/genetics/metabolism ; *Arabidopsis Proteins/genetics/metabolism ; DNA Methylation/*physiology ; *DNA, Plant/genetics/metabolism ; Epigenesis, Genetic/physiology ; Gene Expression Regulation, Plant/physiology ; Genome, Plant/*physiology ; *Seeds/genetics/metabolism ; *Soybeans/genetics/metabolism ; *Transcription Factors/genetics/metabolism ; }, abstract = {The precise mechanisms that control gene activity during seed development remain largely unknown. Previously, we showed that several genes essential for seed development, including those encoding storage proteins, fatty acid biosynthesis enzymes, and transcriptional regulators (e.g., ABI3, FUS3) are located within hypomethylated regions of the soybean genome. These hypomethylated regions are similar to the DNA methylation valleys (DMVs), or canyons, found in mammalian cells. Here, we address the question of the extent to which DMVs are present within seed genomes and what role they might play in seed development. We scanned soybean and Arabidopsis seed genomes from postfertilization through dormancy and germination for regions that contain <5% or <0.4% bulk methylation in CG, CHG, and CHH contexts over all developmental stages. We found that DMVs represent extensive portions of seed genomes, range in size from 5-76 kb, are scattered throughout all chromosomes, and are hypomethylated throughout the plant life cycle. Significantly, DMVs are enriched greatly in transcription factor (TF) genes and other developmental genes that play critical roles in seed formation. Many DMV genes are regulated with respect to seed stage, region, and tissue, and contain H3K4me3, H3K27me3, or bivalent marks that fluctuate during development. Our results indicate that DMVs are a unique regulatory feature of both plant and animal genomes, and that a large number of seed genes are regulated in the absence of methylation changes during development, probably by the action of specific TFs and epigenetic events at the chromatin level.}, } @article {pmid30104382, year = {2018}, author = {Plugis, NM and Weng, N and Zhao, Q and Palanski, BA and Maecker, HT and Habtezion, A and Khosla, C}, title = {Interleukin 4 is inactivated via selective disulfide-bond reduction by extracellular thioredoxin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8781-8786}, pmid = {30104382}, issn = {1091-6490}, support = {R01 DK063158/DK/NIDDK NIH HHS/United States ; R01 DK105263/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Disulfides/immunology/*metabolism ; Humans ; Interleukin-13/immunology/metabolism ; Interleukin-4/immunology/*metabolism ; Mass Spectrometry ; Mice ; Oxidation-Reduction ; Pancreatitis/immunology/*metabolism/pathology ; THP-1 Cells ; Thioredoxins/immunology/*metabolism ; }, abstract = {Thioredoxin 1 (TRX), an essential intracellular redox regulator, is also secreted by mammalian cells. Recently, we showed that TRX activates extracellular transglutaminase 2 via reduction of an allosteric disulfide bond. In an effort to identify other extracellular substrates of TRX, macrophages derived from THP-1 cells were treated with NP161, a small-molecule inhibitor of secreted TRX. NP161 enhanced cytokine outputs of alternatively activated macrophages, suggesting that extracellular TRX regulated the activity of interleukin 4 (IL-4) and/or interleukin 13 (IL-13). To test this hypothesis, the C35S mutant of human TRX was shown to form a mixed disulfide bond with recombinant IL-4 but not IL-13. Kinetic analysis revealed a kcat/KM value of 8.1 μM-1⋅min-1 for TRX-mediated recognition of IL-4, which established this cytokine as the most selective partner of extracellular TRX to date. Mass spectrometry identified the C46-C99 bond of IL-4 as the target of TRX, consistent with the essential role of this disulfide bond in IL-4 activity. To demonstrate the physiological relevance of our biochemical findings, recombinant TRX was shown to attenuate IL-4-dependent proliferation of cultured TF-1 erythroleukemia cells and also to inhibit the progression of chronic pancreatitis in an IL-4-driven mouse model of this disease. By establishing that IL-4 is posttranslationally regulated by TRX-promoted reduction of a disulfide bond, our findings highlight a novel regulatory mechanism of the type 2 immune response that is specific to IL-4 over IL-13.}, } @article {pmid30104381, year = {2018}, author = {Angelani, L and Paoluzzi, M and Parisi, G and Ruocco, G}, title = {Probing the non-Debye low-frequency excitations in glasses through random pinning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8700-8704}, pmid = {30104381}, issn = {1091-6490}, abstract = {We investigate the properties of the low-frequency spectrum in the density of states [Formula: see text] of a 3D model glass former. To magnify the non-Debye sector of the spectrum, we introduce a random pinning field that freezes a finite particle fraction to break the translational invariance and shifts all of the vibrational frequencies of the extended modes toward higher frequencies. We show that non-Debye soft localized modes progressively emerge as the fraction p of pinned particles increases. Moreover, the low-frequency tail of [Formula: see text] goes to zero as a power law [Formula: see text], with [Formula: see text] and [Formula: see text] above a threshold fraction [Formula: see text].}, } @article {pmid30104380, year = {2018}, author = {An, L and Dong, C and Li, J and Chen, J and Yuan, J and Huang, J and Chan, KM and Yu, CH and Huen, MSY}, title = {RNF169 limits 53BP1 deposition at DSBs to stimulate single-strand annealing repair.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8286-E8295}, pmid = {30104380}, issn = {1091-6490}, mesh = {Carrier Proteins/genetics/metabolism ; Cell Line, Tumor ; DNA/genetics/*metabolism ; *DNA Breaks, Double-Stranded ; DNA Repair/*physiology ; Humans ; Nuclear Proteins/genetics/metabolism ; Tumor Suppressor p53-Binding Protein 1/genetics/*metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; }, abstract = {Unrestrained 53BP1 activity at DNA double-strand breaks (DSBs) hampers DNA end resection and upsets DSB repair pathway choice. RNF169 acts as a molecular rheostat to limit 53BP1 deposition at DSBs, but how this fine balance translates to DSB repair control remains undefined. In striking contrast to 53BP1, ChIP analyses of AsiSI-induced DSBs unveiled that RNF169 exhibits robust accumulation at DNA end-proximal regions and preferentially targets resected, RPA-bound DSBs. Accordingly, we found that RNF169 promotes CtIP-dependent DSB resection and favors homology-mediated DSB repair, and further showed that RNF169 dose-dependently stimulates single-strand annealing repair, in part, by alleviating the 53BP1-imposed barrier to DSB end resection. Our results highlight the interplay of RNF169 with 53BP1 in fine-tuning choice of DSB repair pathways.}, } @article {pmid30104379, year = {2018}, author = {Lee, JM and Huddleston, J and Doud, MB and Hooper, KA and Wu, NC and Bedford, T and Bloom, JD}, title = {Deep mutational scanning of hemagglutinin helps predict evolutionary fates of human H3N2 influenza variants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8276-E8285}, pmid = {30104379}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R35 GM119774/GM/NIGMS NIH HHS/United States ; U19 AI117891/AI/NIAID NIH HHS/United States ; R01 AI127893/AI/NIAID NIH HHS/United States ; T32 GM007266/GM/NIGMS NIH HHS/United States ; U54 GM111274/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Dogs ; *Evolution, Molecular ; *Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics ; Humans ; *Influenza A Virus, H3N2 Subtype/chemistry/genetics ; Madin Darby Canine Kidney Cells ; Mutagenesis ; *Mutation ; Protein Domains ; }, abstract = {Human influenza virus rapidly accumulates mutations in its major surface protein hemagglutinin (HA). The evolutionary success of influenza virus lineages depends on how these mutations affect HA's functionality and antigenicity. Here we experimentally measure the effects on viral growth in cell culture of all single amino acid mutations to the HA from a recent human H3N2 influenza virus strain. We show that mutations that are measured to be more favorable for viral growth are enriched in evolutionarily successful H3N2 viral lineages relative to mutations that are measured to be less favorable for viral growth. Therefore, despite the well-known caveats about cell-culture measurements of viral fitness, such measurements can still be informative for understanding evolution in nature. We also compare our measurements for H3 HA to similar data previously generated for a distantly related H1 HA and find substantial differences in which amino acids are preferred at many sites. For instance, the H3 HA has less disparity in mutational tolerance between the head and stalk domains than the H1 HA. Overall, our work suggests that experimental measurements of mutational effects can be leveraged to help understand the evolutionary fates of viral lineages in nature-but only when the measurements are made on a viral strain similar to the ones being studied in nature.}, } @article {pmid30104378, year = {2018}, author = {Babino, A and Makse, HA and DiTella, R and Sigman, M}, title = {Maintaining trust when agents can engage in self-deception.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8728-8733}, pmid = {30104378}, issn = {1091-6490}, support = {R01 EB022720/EB/NIBIB NIH HHS/United States ; }, mesh = {*Cooperative Behavior ; *Culture ; *Deception ; Humans ; *Models, Theoretical ; *Prisoner Dilemma ; *Professional Misconduct ; }, abstract = {The coexistence of cooperation and selfish instincts is a remarkable characteristic of humans. Psychological research has unveiled the cognitive mechanisms behind self-deception. Two important findings are that a higher ambiguity about others' social preferences leads to a higher likelihood of acting selfishly and that agents acting selfishly will increase their belief that others are also selfish. In this work, we posit a mathematical model of these mechanisms and explain their impact on the undermining of a global cooperative society. We simulate the behavior of agents playing a prisoner's dilemma game in a random network of contacts. We endow each agent with these two self-deception mechanisms which bias her toward thinking that the other agent will defect. We study behavior when a fraction of agents with the "always defect" strategy is introduced in the network. Depending on the magnitude of the biases the players could start a cascade of defection or isolate the defectors. We find that there are thresholds above which the system approaches a state of complete distrust.}, } @article {pmid30104377, year = {2018}, author = {Xu, S and Liu, P and Chen, Y and Chen, Y and Zhang, W and Zhao, H and Cao, Y and Wang, F and Jiang, N and Lin, S and Li, B and Zhang, Z and Wei, Z and Fan, Y and Jin, Y and He, L and Zhou, R and Dekker, JD and Tucker, HO and Fisher, SE and Yao, Z and Liu, Q and Xia, X and Guo, X}, title = {Foxp2 regulates anatomical features that may be relevant for vocal behaviors and bipedal locomotion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8799-8804}, pmid = {30104377}, issn = {1091-6490}, support = {R01 CA031534/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bone Remodeling/*genetics ; *Forkhead Transcription Factors/genetics/metabolism ; Hindlimb/metabolism ; Humans ; Locomotion/*genetics ; Mice ; Mice, Knockout ; *Mutation ; *Repressor Proteins/genetics/metabolism ; Skull/*metabolism ; *Vocalization, Animal ; }, abstract = {Fundamental human traits, such as language and bipedalism, are associated with a range of anatomical adaptations in craniofacial shaping and skeletal remodeling. However, it is unclear how such morphological features arose during hominin evolution. FOXP2 is a brain-expressed transcription factor implicated in a rare disorder involving speech apraxia and language impairments. Analysis of its evolutionary history suggests that this gene may have contributed to the emergence of proficient spoken language. In the present study, through analyses of skeleton-specific knockout mice, we identified roles of Foxp2 in skull shaping and bone remodeling. Selective ablation of Foxp2 in cartilage disrupted pup vocalizations in a similar way to that of global Foxp2 mutants, which may be due to pleiotropic effects on craniofacial morphogenesis. Our findings also indicate that Foxp2 helps to regulate strength and length of hind limbs and maintenance of joint cartilage and intervertebral discs, which are all anatomical features that are susceptible to adaptations for bipedal locomotion. In light of the known roles of Foxp2 in brain circuits that are important for motor skills and spoken language, we suggest that this gene may have been well placed to contribute to coevolution of neural and anatomical adaptations related to speech and bipedal locomotion.}, } @article {pmid30104376, year = {2018}, author = {Glasser, NR and Oyala, PH and Osborne, TH and Santini, JM and Newman, DK}, title = {Structural and mechanistic analysis of the arsenate respiratory reductase provides insight into environmental arsenic transformations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {37}, pages = {E8614-E8623}, pmid = {30104376}, issn = {1091-6490}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; R01 AI127850/AI/NIAID NIH HHS/United States ; BB/N012674/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Arsenate Reductases/chemistry/genetics/*metabolism ; Arsenates/chemistry/*metabolism ; Arsenic/chemistry/*metabolism ; Arsenites/chemistry/metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Crystallography, X-Ray ; Gene Expression Regulation, Bacterial ; Kinetics ; Models, Molecular ; Oxidoreductases/chemistry/genetics/metabolism ; Protein Binding ; Protein Domains ; Sequence Homology, Amino Acid ; Shewanella/genetics/*metabolism ; }, abstract = {Arsenate respiration by bacteria was discovered over two decades ago and is catalyzed by diverse organisms using the well-conserved Arr enzyme complex. Until now, the mechanisms underpinning this metabolism have been relatively opaque. Here, we report the structure of an Arr complex (solved by X-ray crystallography to 1.6-Å resolution), which was enabled by an improved Arr expression method in the genetically tractable arsenate respirer Shewanella sp. ANA-3. We also obtained structures bound with the substrate arsenate (1.8 Å), the product arsenite (1.8 Å), and the natural inhibitor phosphate (1.7 Å). The structures reveal a conserved active-site motif that distinguishes Arr [(R/K)GRY] from the closely related arsenite respiratory oxidase (Arx) complex (XGRGWG). Arr activity assays using methyl viologen as the electron donor and arsenate as the electron acceptor display two-site ping-pong kinetics. A Mo(V) species was detected with EPR spectroscopy, which is typical for proteins with a pyranopterin guanine dinucleotide cofactor. Arr is an extraordinarily fast enzyme that approaches the diffusion limit (Km = 44.6 ± 1.6 μM, kcat = 9,810 ± 220 seconds-1), and phosphate is a competitive inhibitor of arsenate reduction (Ki = 325 ± 12 μM). These observations, combined with knowledge of typical sedimentary arsenate and phosphate concentrations and known rates of arsenate desorption from minerals in the presence of phosphate, suggest that (i) arsenate desorption limits microbiologically induced arsenate reductive mobilization and (ii) phosphate enhances arsenic mobility by stimulating arsenate desorption rather than by inhibiting it at the enzymatic level.}, } @article {pmid30104375, year = {2018}, author = {Bang, I and Kim, HR and Beaven, AH and Kim, J and Ko, SB and Lee, GR and Kan, W and Lee, H and Im, W and Seok, C and Chung, KY and Choi, HJ}, title = {Biophysical and functional characterization of Norrin signaling through Frizzled4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8787-8792}, pmid = {30104375}, issn = {1091-6490}, mesh = {Animals ; Eye Proteins/*chemistry/metabolism ; Frizzled Receptors/*chemistry/metabolism ; Mice ; Nerve Tissue Proteins/*chemistry/metabolism ; Protein Binding ; Protein Domains ; Protein Structure, Quaternary ; Protein Structure, Secondary ; Structure-Activity Relationship ; *Wnt Signaling Pathway ; }, abstract = {Wnt signaling is initiated by Wnt ligand binding to the extracellular ligand binding domain, called the cysteine-rich domain (CRD), of a Frizzled (Fzd) receptor. Norrin, an atypical Fzd ligand, specifically interacts with Fzd4 to activate β-catenin-dependent canonical Wnt signaling. Much of the molecular basis that confers Norrin selectivity in binding to Fzd4 was revealed through the structural study of the Fzd4CRD-Norrin complex. However, how the ligand interaction, seemingly localized at the CRD, is transmitted across full-length Fzd4 to the cytoplasm remains largely unknown. Here, we show that a flexible linker domain, which connects the CRD to the transmembrane domain, plays an important role in Norrin signaling. The linker domain directly contributes to the high-affinity interaction between Fzd4 and Norrin as shown by ∼10-fold higher binding affinity of Fzd4CRD to Norrin in the presence of the linker. Swapping the Fzd4 linker with the Fzd5 linker resulted in the loss of Norrin signaling, suggesting the importance of the linker in ligand-specific cellular response. In addition, structural dynamics of Fzd4 associated with Norrin binding investigated by hydrogen/deuterium exchange MS revealed Norrin-induced conformational changes on the linker domain and the intracellular loop 3 (ICL3) region of Fzd4. Cell-based functional assays showed that linker deletion, L430A and L433A mutations at ICL3, and C-terminal tail truncation displayed reduced β-catenin-dependent signaling activity, indicating the functional significance of these sites. Together, our results provide functional and biochemical dissection of Fzd4 in Norrin signaling.}, } @article {pmid30104374, year = {2018}, author = {Sun, AX and Londono, R and Hudnall, ML and Tuan, RS and Lozito, TP}, title = {Differences in neural stem cell identity and differentiation capacity drive divergent regenerative outcomes in lizards and salamanders.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8256-E8265}, pmid = {30104374}, issn = {1091-6490}, support = {R01 GM115444/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*physiology ; Ependyma/metabolism ; Lizards/*physiology ; Neural Stem Cells/*metabolism ; Regeneration/*physiology ; Species Specificity ; Spinal Cord/*physiology ; Urodela ; }, abstract = {While lizards and salamanders both exhibit the ability to regenerate amputated tails, the outcomes achieved by each are markedly different. Salamanders, such as Ambystoma mexicanum, regenerate nearly identical copies of original tails. Regenerated lizard tails, however, exhibit important morphological differences compared with originals. Some of these differences concern dorsoventral patterning of regenerated skeletal and spinal cord tissues; regenerated salamander tail tissues exhibit dorsoventral patterning, while regrown lizard tissues do not. Additionally, regenerated lizard tails lack characteristically roof plate-associated structures, such as dorsal root ganglia. We hypothesized that differences in neural stem cells (NSCs) found in the ependyma of regenerated spinal cords account for these divergent regenerative outcomes. Through a combination of immunofluorescent staining, RT-PCR, hedgehog regulation, and transcriptome analysis, we analyzed NSC-dependent tail regeneration. Both salamander and lizard Sox2+ NSCs form neurospheres in culture. While salamander neurospheres exhibit default roof plate identity, lizard neurospheres exhibit default floor plate. Hedgehog signaling regulates dorsalization/ventralization of salamander, but not lizard, NSCs. Examination of NSC differentiation potential in vitro showed that salamander NSCs are capable of neural differentiation into multiple lineages, whereas lizard NSCs are not, which was confirmed by in vivo spinal cord transplantations. Finally, salamander NSCs xenogeneically transplanted into regenerating lizard tail spinal cords were influenced by native lizard NSC hedgehog signals, which favored salamander NSC floor plate differentiation. These findings suggest that NSCs in regenerated lizard and salamander spinal cords are distinct cell populations, and these differences contribute to the vastly different outcomes observed in tail regeneration.}, } @article {pmid30104373, year = {2018}, author = {Fernández, PJ and Mongle, CS and Leakey, L and Proctor, DJ and Orr, CM and Patel, BA and Almécija, S and Tocheri, MW and Jungers, WL}, title = {Evolution and function of the hominin forefoot.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8746-8751}, pmid = {30104373}, issn = {1091-6490}, support = {P40 OD012217/OD/NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; *Hominidae/anatomy & histology/physiology ; *Metatarsal Bones/anatomy & histology/physiology ; *Phylogeny ; }, abstract = {The primate foot functions as a grasping organ. As such, its bones, soft tissues, and joints evolved to maximize power and stability in a variety of grasping configurations. Humans are the obvious exception to this primate pattern, with feet that evolved to support the unique biomechanical demands of bipedal locomotion. Of key functional importance to bipedalism is the morphology of the joints at the forefoot, known as the metatarsophalangeal joints (MTPJs), but a comprehensive analysis of hominin MTPJ morphology is currently lacking. Here we present the results of a multivariate shape and Bayesian phylogenetic comparative analyses of metatarsals (MTs) from a broad selection of anthropoid primates (including fossil apes and stem catarrhines) and most of the early hominin pedal fossil record, including the oldest hominin for which good pedal remains exist, Ardipithecus ramidus Results corroborate the importance of specific bony morphologies such as dorsal MT head expansion and "doming" to the evolution of terrestrial bipedalism in hominins. Further, our evolutionary models reveal that the MT1 of Ar. ramidus shifts away from the reconstructed optimum of our last common ancestor with apes, but not necessarily in the direction of modern humans. However, the lateral rays of Ar. ramidus are transformed in a more human-like direction, suggesting that they were the digits first recruited by hominins into the primary role of terrestrial propulsion. This pattern of evolutionary change is seen consistently throughout the evolution of the foot, highlighting the mosaic nature of pedal evolution and the emergence of a derived, modern hallux relatively late in human evolution.}, } @article {pmid30104372, year = {2018}, author = {Tomasello, M}, title = {How children come to understand false beliefs: A shared intentionality account.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8491-8498}, pmid = {30104372}, issn = {1091-6490}, mesh = {Child ; Child, Preschool ; Comprehension/*physiology ; *Culture ; Female ; Humans ; Imagination/*physiology ; Male ; *Social Behavior ; }, abstract = {To predict and explain the behavior of others, one must understand that their actions are determined not by reality but by their beliefs about reality. Classically, children come to understand beliefs, including false beliefs, at about 4-5 y of age, but recent studies using different response measures suggest that even infants (and apes!) have some skills as well. Resolving this discrepancy is not possible with current theories based on individual cognition. Instead, what is needed is an account recognizing that the key processes in constructing an understanding of belief are social and mental coordination with other persons and their (sometimes conflicting) perspectives. Engaging in such social and mental coordination involves species-unique skills and motivations of shared intentionality, especially as they are manifest in joint attention and linguistic communication, as well as sophisticated skills of executive function to coordinate the different perspectives involved. This shared intentionality account accords well with documented differences in the cognitive capacities of great apes and human children, and it explains why infants and apes pass some versions of false-belief tasks whereas only older children pass others.}, } @article {pmid30104371, year = {2018}, author = {Bernstein, E and Shore, J and Lazer, D}, title = {How intermittent breaks in interaction improve collective intelligence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8734-8739}, pmid = {30104371}, issn = {1091-6490}, mesh = {Adult ; *Cooperative Behavior ; Female ; Humans ; *Intelligence ; Male ; *Problem Solving ; }, abstract = {People influence each other when they interact to solve problems. Such social influence introduces both benefits (higher average solution quality due to exploitation of existing answers through social learning) and costs (lower maximum solution quality due to a reduction in individual exploration for novel answers) relative to independent problem solving. In contrast to prior work, which has focused on how the presence and network structure of social influence affect performance, here we investigate the effects of time. We show that when social influence is intermittent it provides the benefits of constant social influence without the costs. Human subjects solved the canonical traveling salesperson problem in groups of three, randomized into treatments with constant social influence, intermittent social influence, or no social influence. Groups in the intermittent social-influence treatment found the optimum solution frequently (like groups without influence) but had a high mean performance (like groups with constant influence); they learned from each other, while maintaining a high level of exploration. Solutions improved most on rounds with social influence after a period of separation. We also show that storing subjects' best solutions so that they could be reloaded and possibly modified in subsequent rounds-a ubiquitous feature of personal productivity software-is similar to constant social influence: It increases mean performance but decreases exploration.}, } @article {pmid30104370, year = {2018}, author = {Viegas, J}, title = {Profile of Michael Tomasello.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8466-8468}, pmid = {30104370}, issn = {1091-6490}, mesh = {Anthropology/*history ; History, 20th Century ; History, 21st Century ; Humans ; Portraits as Topic ; }, } @article {pmid30104369, year = {2018}, author = {Brandon, A and List, JA and Metcalfe, RD and Price, MK and Rundhammer, F}, title = {Testing for crowd out in social nudges: Evidence from a natural field experiment in the market for electricity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802874115}, pmid = {30104369}, issn = {1091-6490}, abstract = {This study considers the response of household electricity consumption to social nudges during peak load events. Our investigation considers two social nudges. The first targets conservation during peak load events, while the second promotes aggregate conservation. Using data from a natural field experiment with 42,100 households, we find that both social nudges reduce peak load electricity consumption by 2 to 4% when implemented in isolation and by nearly 7% when implemented in combination. These findings suggest an important role for social nudges in the regulation of electricity markets and a limited role for crowd out effects.}, } @article {pmid30104368, year = {2018}, author = {Imam, H and Khan, M and Gokhale, NS and McIntyre, ABR and Kim, GW and Jang, JY and Kim, SJ and Mason, CE and Horner, SM and Siddiqui, A}, title = {N6-methyladenosine modification of hepatitis B virus RNA differentially regulates the viral life cycle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8829-8834}, pmid = {30104368}, issn = {1091-6490}, support = {R01 MH117406/MH/NIMH NIH HHS/United States ; R01 AI125416/AI/NIAID NIH HHS/United States ; R56 AI139234/AI/NIAID NIH HHS/United States ; R01 AI125350/AI/NIAID NIH HHS/United States ; R21 AI129851/AI/NIAID NIH HHS/United States ; }, mesh = {Adenosine/*analogs & derivatives/genetics/metabolism ; Gene Expression Regulation, Viral/*physiology ; Hep G2 Cells ; Hepatitis B virus/*physiology ; Humans ; *Nucleic Acid Conformation ; *RNA Stability ; RNA, Viral/*biosynthesis/genetics ; Reverse Transcription/physiology ; Viral Proteins/biosynthesis/genetics ; }, abstract = {N6-methyladenosine (m6A) RNA methylation is the most abundant epitranscriptomic modification of eukaryotic messenger RNAs (mRNAs). Previous reports have found m6A on both cellular and viral transcripts and defined its role in regulating numerous biological processes, including viral infection. Here, we show that m6A and its associated machinery regulate the life cycle of hepatitis B virus (HBV). HBV is a DNA virus that completes its life cycle via an RNA intermediate, termed pregenomic RNA (pgRNA). Silencing of enzymes that catalyze the addition of m6A to RNA resulted in increased HBV protein expression, but overall reduced reverse transcription of the pgRNA. We mapped the m6A site in the HBV RNA and found that a conserved m6A consensus motif situated within the epsilon stem loop structure, is the site for m6A modification. The epsilon stem loop is located in the 3' terminus of all HBV mRNAs and at both the 5' and 3' termini of the pgRNA. Mutational analysis of the identified m6A site in the 5' epsilon stem loop of pgRNA revealed that m6A at this site is required for efficient reverse transcription of pgRNA, while m6A methylation of the 3' epsilon stem loop results in destabilization of all HBV transcripts, suggesting that m6A has dual regulatory function for HBV RNA. Overall, this study reveals molecular insights into how m6A regulates HBV gene expression and reverse transcription, leading to an increased level of understanding of the HBV life cycle.}, } @article {pmid30104367, year = {2018}, author = {Roffet-Salque, M and Marciniak, A and Valdes, PJ and Pawłowska, K and Pyzel, J and Czerniak, L and Krüger, M and Roberts, CN and Pitter, S and Evershed, RP}, title = {Evidence for the impact of the 8.2-kyBP climate event on Near Eastern early farmers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8705-8709}, pmid = {30104367}, issn = {1091-6490}, abstract = {The 8.2-thousand years B.P. event is evident in multiple proxy records across the globe, showing generally dry and cold conditions for ca. 160 years. Environmental changes around the event are mainly detected using geochemical or palynological analyses of ice cores, lacustrine, marine, and other sediments often distant from human settlements. The Late Neolithic excavated area of the archaeological site of Çatalhöyük East [Team Poznań (TP) area] was occupied for four centuries in the ninth and eighth millennia B.P., thus encompassing the 8.2-thousand years B.P. climatic event. A Bayesian analysis of 56 radiocarbon dates yielded a high-resolution chronological model comprising six building phases, with dates ranging from before 8325-8205 to 7925-7815 calibrated years (cal) B.P. Here, we correlate an onsite paleoclimate record constructed from δ2H values of lipid biomarkers preserved in pottery vessels recovered from these buildings with changes in architectural, archaeozoological, and consumption records from well-documented archaeological contexts. The overall sequence shows major changes in husbandry and consumption practices at ca. 8.2 thousand years B.P., synchronous with variations in the δ2H values of the animal fat residues. Changes in paleoclimate and archaeological records seem connected with the patterns of atmospheric precipitation during the occupation of the TP area predicted by climate modeling. Our multiproxy approach uses records derived directly from documented archaeological contexts. Through this, we provide compelling evidence for the specific impacts of the 8.2-thousand years B.P. climatic event on the economic and domestic activities of pioneer Neolithic farmers, influencing decisions relating to settlement planning and food procurement strategies.}, } @article {pmid30104366, year = {2018}, author = {Jenkins, KA and Fossat, MJ and Zhang, S and Rai, DK and Klein, S and Gillilan, R and White, Z and Gerlich, G and McCallum, SA and Winter, R and Gruner, SM and Barrick, D and Royer, CA}, title = {The consequences of cavity creation on the folding landscape of a repeat protein depend upon context.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8153-E8161}, pmid = {30104366}, issn = {1091-6490}, support = {P41 GM103485/GM/NIGMS NIH HHS/United States ; R01 GM068462/GM/NIGMS NIH HHS/United States ; T32 GM008403/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; Intracellular Signaling Peptides and Proteins/*chemistry/genetics ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Protein Domains ; Protein Folding ; Protein Stability ; Scattering, Small Angle ; Structure-Activity Relationship ; X-Ray Diffraction ; }, abstract = {The effect of introducing internal cavities on protein native structure and global stability has been well documented, but the consequences of these packing defects on folding free-energy landscapes have received less attention. We investigated the effects of cavity creation on the folding landscape of the leucine-rich repeat protein pp32 by high-pressure (HP) and urea-dependent NMR and high-pressure small-angle X-ray scattering (HPSAXS). Despite a modest global energetic perturbation, cavity creation in the N-terminal capping motif (N-cap) resulted in very strong deviation from two-state unfolding behavior. In contrast, introduction of a cavity in the most stable, C-terminal half of pp32 led to highly concerted unfolding, presumably because the decrease in stability by the mutations attenuated the N- to C-terminal stability gradient present in WT pp32. Interestingly, enlarging the central cavity of the protein led to the population under pressure of a distinct intermediate in which the N-cap and repeats 1-4 were nearly completely unfolded, while the fifth repeat and the C-terminal capping motif remained fully folded. Thus, despite modest effects on global stability, introducing internal cavities can have starkly distinct repercussions on the conformational landscape of a protein, depending on their structural and energetic context.}, } @article {pmid30104365, year = {2018}, author = {}, title = {Correction for Wang et al., Molecular origin of the weak susceptibility of kinesin velocity to loads and its relation to the collective behavior of kinesins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8104}, doi = {10.1073/pnas.1812987115}, pmid = {30104365}, issn = {1091-6490}, } @article {pmid30104364, year = {2018}, author = {Kanaji, T and Vo, MN and Kanaji, S and Zarpellon, A and Shapiro, R and Morodomi, Y and Yuzuriha, A and Eto, K and Belani, R and Do, MH and Yang, XL and Ruggeri, ZM and Schimmel, P}, title = {Tyrosyl-tRNA synthetase stimulates thrombopoietin-independent hematopoiesis accelerating recovery from thrombocytopenia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8228-E8235}, pmid = {30104364}, issn = {1091-6490}, support = {R01 CA092577/CA/NCI NIH HHS/United States ; R01 HL117722/HL/NHLBI NIH HHS/United States ; R01 HL129011/HL/NHLBI NIH HHS/United States ; R01 HL135294/HL/NHLBI NIH HHS/United States ; }, mesh = {Blood Platelets/*metabolism/pathology ; Cell Culture Techniques ; Cells, Cultured ; Female ; *Hematopoiesis ; Hematopoietic Stem Cells/metabolism/pathology ; Humans ; Induced Pluripotent Stem Cells/metabolism/pathology ; Male ; Megakaryocytes/*metabolism/pathology ; *Polyploidy ; Signal Transduction ; Thrombocytopenia/*metabolism/pathology ; Thrombopoietin/metabolism ; Tyrosine-tRNA Ligase/*metabolism ; }, abstract = {New mechanisms behind blood cell formation continue to be uncovered, with therapeutic approaches for hematological diseases being of great interest. Here we report an enzyme in protein synthesis, known for cell-based activities beyond translation, is a factor inducing megakaryocyte-biased hematopoiesis, most likely under stress conditions. We show an activated form of tyrosyl-tRNA synthetase (YRSACT), prepared either by rationally designed mutagenesis or alternative splicing, induces expansion of a previously unrecognized high-ploidy Sca-1+ megakaryocyte population capable of accelerating platelet replenishment after depletion. Moreover, YRSACT targets monocytic cells to induce secretion of transacting cytokines that enhance megakaryocyte expansion stimulating the Toll-like receptor/MyD88 pathway. Platelet replenishment by YRSACT is independent of thrombopoietin (TPO), as evidenced by expansion of the megakaryocytes from induced pluripotent stem cell-derived hematopoietic stem cells from a patient deficient in TPO signaling. We suggest megakaryocyte-biased hematopoiesis induced by YRSACT offers new approaches for treating thrombocytopenia, boosting yields from cell-culture production of platelet concentrates for transfusion, and bridging therapy for hematopoietic stem cell transplantation.}, } @article {pmid30104363, year = {2018}, author = {Tang, H and Schrimpf, M and Lotter, W and Moerman, C and Paredes, A and Ortega Caro, J and Hardesty, W and Cox, D and Kreiman, G}, title = {Recurrent computations for visual pattern completion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8835-8840}, pmid = {30104363}, issn = {1091-6490}, support = {R01 EY026025/EY/NEI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *Computer Simulation ; Female ; Humans ; Male ; *Models, Neurological ; Pattern Recognition, Visual/*physiology ; }, abstract = {Making inferences from partial information constitutes a critical aspect of cognition. During visual perception, pattern completion enables recognition of poorly visible or occluded objects. We combined psychophysics, physiology, and computational models to test the hypothesis that pattern completion is implemented by recurrent computations and present three pieces of evidence that are consistent with this hypothesis. First, subjects robustly recognized objects even when they were rendered <15% visible, but recognition was largely impaired when processing was interrupted by backward masking. Second, invasive physiological responses along the human ventral cortex exhibited visually selective responses to partially visible objects that were delayed compared with whole objects, suggesting the need for additional computations. These physiological delays were correlated with the effects of backward masking. Third, state-of-the-art feed-forward computational architectures were not robust to partial visibility. However, recognition performance was recovered when the model was augmented with attractor-based recurrent connectivity. The recurrent model was able to predict which images of heavily occluded objects were easier or harder for humans to recognize, could capture the effect of introducing a backward mask on recognition behavior, and was consistent with the physiological delays along the human ventral visual stream. These results provide a strong argument of plausibility for the role of recurrent computations in making visual inferences from partial information.}, } @article {pmid30104362, year = {2018}, author = {Karra, R and Foglia, MJ and Choi, WY and Belliveau, C and DeBenedittis, P and Poss, KD}, title = {Vegfaa instructs cardiac muscle hyperplasia in adult zebrafish.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8805-8810}, pmid = {30104362}, issn = {1091-6490}, support = {F30 HL126487/HL/NHLBI NIH HHS/United States ; K08 HL116485/HL/NHLBI NIH HHS/United States ; R01 HL081674/HL/NHLBI NIH HHS/United States ; R01 HL131319/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cardiomegaly/genetics/*metabolism/pathology ; Epithelial-Mesenchymal Transition ; Hyperplasia/genetics/metabolism/pathology ; Myocardium/*metabolism/pathology ; Myocytes, Cardiac/*metabolism/pathology ; Vascular Endothelial Growth Factor A/genetics/*metabolism ; Zebrafish/genetics/*metabolism ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {During heart development and regeneration, coronary vascularization is tightly coupled with cardiac growth. Although inhibiting vascularization causes defects in the innate regenerative response of zebrafish to heart injury, angiogenic signals are not known to be sufficient for triggering regeneration events. Here, by using a transgenic reporter strain, we found that regulatory sequences of the angiogenic factor vegfaa are active in epicardial cells of uninjured animals, as well as in epicardial and endocardial tissue adjacent to regenerating muscle upon injury. Additionally, we find that induced cardiac overexpression of vegfaa in zebrafish results in overt hyperplastic thickening of the myocardial wall, accompanied by indicators of angiogenesis, epithelial-to-mesenchymal transition, and cardiomyocyte regeneration programs. Unexpectedly, vegfaa overexpression in the context of cardiac injury enabled ectopic cardiomyogenesis but inhibited regeneration at the site of the injury. Our findings identify Vegfa as one of a select few known factors sufficient to activate adult cardiomyogenesis, while also illustrating how instructive factors for heart regeneration require spatiotemporal control for efficacy.}, } @article {pmid30104361, year = {2018}, author = {Zhang, Z and Niu, B and Ji, D and Li, M and Li, K and James, AA and Tan, A and Huang, Y}, title = {Silkworm genetic sexing through W chromosome-linked, targeted gene integration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8752-8756}, pmid = {30104361}, issn = {1091-6490}, support = {27304C2054/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Bombyx/*genetics ; *CRISPR-Cas Systems ; Chromosomes, Insect/*genetics ; Female ; Gene Editing/*methods ; Male ; Sex Chromosomes/*genetics ; *Sex Determination Processes ; }, abstract = {Sex separation methods are critical for genetic sexing systems in commercial insect production and sterile insect techniques. Integration of selectable marker genes into a sex chromosome is particularly useful in insects with a heterogametic sex determination system. Here, we describe targeted gene integration of fluorescent marker expression cassettes into a randomly amplified polymorphic DNA (RAPD) marker region in the W chromosome of the lepidopteran model insect Bombyx mori using transcriptional activator-like effector nuclease (TALEN)-mediated genome editing. This silkworm strain shows ubiquitous female-specific red or green fluorescence from the embryonic to adult stages. Furthermore, we developed a binary, female-specific, embryonic lethality system combining the TALEN and the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) technology. This system includes one strain with TALEN-mediated, W-specific Cas9 expression driven by the silkworm germ cell-specific nanos (nos) promoter and another strain with U6-derived single-guide RNA (sgRNA) expression targeting transformer 2 (tra2), an essential gene for silkworm embryonic development. Filial 1 (F1) hybrids exhibit complete female-specific lethality during embryonic stages. Our study provides a promising approach for B. mori genetic sexing and sheds light on developing sterile insect techniques in other insect species, especially in lepidopteran pests with WZ/ZZ sex chromosome systems.}, } @article {pmid30104360, year = {2018}, author = {Wang, Z and Guo, H and Shao, S and Saghayezhian, M and Li, J and Fittipaldi, R and Vecchione, A and Siwakoti, P and Zhu, Y and Zhang, J and Plummer, EW}, title = {Designing antiphase boundaries by atomic control of heterointerfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9485-9490}, pmid = {30104360}, issn = {1091-6490}, abstract = {Extended defects are known to have critical influences in achieving desired material performance. However, the nature of extended defect generation is highly elusive due to the presence of multiple nucleation mechanisms with close energetics. A strategy to design extended defects in a simple and clean way is thus highly desirable to advance the understanding of their role, improve material quality, and serve as a unique playground to discover new phenomena. In this work, we report an approach to create planar extended defects-antiphase boundaries (APB) -with well-defined origins via the combination of advanced growth, atomic-resolved electron microscopy, first-principals calculations, and defect theory. In La2/3Sr1/3MnO3 thin film grown on Sr2RuO4 substrate, APBs in the film naturally nucleate at the step on the substrate/film interface. For a single step, the generated APBs tend to be nearly perpendicular to the interface and propragate toward the film surface. Interestingly, when two steps are close to each other, two corresponding APBs communicate and merge together, forming a unique triangle-shaped defect domain boundary. Such behavior has been ascribed, in general, to the minimization of the surface energy of the APB. Atomic-resolved electron microscopy shows that these APBs have an intriguing antipolar structure phase, thus having the potential as a general recipe to achieve ferroelectric-like domain walls for high-density nonvolatile memory.}, } @article {pmid30104359, year = {2018}, author = {Pataki, CI and Rodrigues, J and Zhang, L and Qian, J and Efron, B and Hastie, T and Elias, JE and Levitt, M and Kopito, RR}, title = {Proteomic analysis of monolayer-integrated proteins on lipid droplets identifies amphipathic interfacial α-helical membrane anchors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8172-E8180}, pmid = {30104359}, issn = {1091-6490}, support = {R01 EB001988/EB/NIBIB NIH HHS/United States ; R01 GM074874/GM/NIGMS NIH HHS/United States ; R35 GM122543/GM/NIGMS NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; }, mesh = {HEK293 Cells ; Humans ; Lipid Droplets ; Membrane Proteins/*chemistry/genetics/metabolism ; Mutagenesis ; Protein Domains ; Protein Structure, Secondary ; *Proteomics ; }, abstract = {Despite not spanning phospholipid bilayers, monotopic integral proteins (MIPs) play critical roles in organizing biochemical reactions on membrane surfaces. Defining the structural basis by which these proteins are anchored to membranes has been hampered by the paucity of unambiguously identified MIPs and a lack of computational tools that accurately distinguish monolayer-integrating motifs from bilayer-spanning transmembrane domains (TMDs). We used quantitative proteomics and statistical modeling to identify 87 high-confidence candidate MIPs in lipid droplets, including 21 proteins with predicted TMDs that cannot be accommodated in these monolayer-enveloped organelles. Systematic cysteine-scanning mutagenesis showed the predicted TMD of one candidate MIP, DHRS3, to be a partially buried amphipathic α-helix in both lipid droplet monolayers and the cytoplasmic leaflet of endoplasmic reticulum membrane bilayers. Coarse-grained molecular dynamics simulations support these observations, suggesting that this helix is most stable at the solvent-membrane interface. The simulations also predicted similar interfacial amphipathic helices when applied to seven additional MIPs from our dataset. Our findings suggest that interfacial helices may be a common motif by which MIPs are integrated into membranes, and provide high-throughput methods to identify and study MIPs.}, } @article {pmid30104358, year = {2018}, author = {Vaughan, RM and Dickson, BM and Whelihan, MF and Johnstone, AL and Cornett, EM and Cheek, MA and Ausherman, CA and Cowles, MW and Sun, ZW and Rothbart, SB}, title = {Chromatin structure and its chemical modifications regulate the ubiquitin ligase substrate selectivity of UHRF1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8775-8780}, pmid = {30104358}, issn = {1091-6490}, support = {R35 GM124736/GM/NIGMS NIH HHS/United States ; R43 CA212733/CA/NCI NIH HHS/United States ; R44 CA212733/CA/NCI NIH HHS/United States ; }, mesh = {*CCAAT-Enhancer-Binding Proteins/chemistry/metabolism ; *Chromatin/chemistry/metabolism ; DNA (Cytosine-5-)-Methyltransferase 1/chemistry/metabolism ; *DNA Methylation ; *Histones/chemistry/metabolism ; Humans ; *Models, Biological ; Substrate Specificity ; *Ubiquitination ; }, abstract = {Mitotic inheritance of DNA methylation patterns is facilitated by UHRF1, a DNA- and histone-binding E3 ubiquitin ligase that helps recruit the maintenance DNA methyltransferase DNMT1 to replicating chromatin. The DNA methylation maintenance function of UHRF1 is dependent on its ability to bind chromatin, where it facilitates monoubiquitination of histone H3 at lysines 18 and 23, a docking site for DNMT1. Because of technical limitations, this model of UHRF1-dependent DNA methylation inheritance has been constructed largely based on genetics and biochemical observations querying methylated DNA oligonucleotides, synthetic histone peptides, and heterogeneous chromatin extracted from cells. Here, we construct semisynthetic mononucleosomes harboring defined histone and DNA modifications and perform rigorous analysis of UHRF1 binding and enzymatic activity with these reagents. We show that multivalent engagement of nucleosomal linker DNA and dimethylated lysine 9 on histone H3 directs UHRF1 ubiquitin ligase activity toward histone substrates. Notably, we reveal a molecular switch, stimulated by recognition of hemimethylated DNA, which redirects UHRF1 ubiquitin ligase activity away from histones in favor of robust autoubiquitination. Our studies support a noncompetitive model for UHRF1 and DNMT1 chromatin recruitment to replicating chromatin and define a role for hemimethylated linker DNA as a regulator of UHRF1 ubiquitin ligase substrate selectivity.}, } @article {pmid30104357, year = {2018}, author = {Sun, Y and Kotiuga, M and Lim, D and Narayanan, B and Cherukara, M and Zhang, Z and Dong, Y and Kou, R and Sun, CJ and Lu, Q and Waluyo, I and Hunt, A and Tanaka, H and Hattori, AN and Gamage, S and Abate, Y and Pol, VG and Zhou, H and Sankaranarayanan, SKRS and Yildiz, B and Rabe, KM and Ramanathan, S}, title = {Strongly correlated perovskite lithium ion shuttles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {39}, pages = {9672-9677}, pmid = {30104357}, issn = {1091-6490}, abstract = {Solid-state ion shuttles are of broad interest in electrochemical devices, nonvolatile memory, neuromorphic computing, and biomimicry utilizing synthetic membranes. Traditional design approaches are primarily based on substitutional doping of dissimilar valent cations in a solid lattice, which has inherent limits on dopant concentration and thereby ionic conductivity. Here, we demonstrate perovskite nickelates as Li-ion shuttles with simultaneous suppression of electronic transport via Mott transition. Electrochemically lithiated SmNiO3 (Li-SNO) contains a large amount of mobile Li+ located in interstitial sites of the perovskite approaching one dopant ion per unit cell. A significant lattice expansion associated with interstitial doping allows for fast Li+ conduction with reduced activation energy. We further present a generalization of this approach with results on other rare-earth perovskite nickelates as well as dopants such as Na+ The results highlight the potential of quantum materials and emergent physics in design of ion conductors.}, } @article {pmid30104356, year = {2018}, author = {Zhao, TC and Kuhl, PK}, title = {Linguistic effect on speech perception observed at the brainstem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8716-8721}, pmid = {30104356}, issn = {1091-6490}, mesh = {Adult ; Brain Stem/*physiology ; Female ; Humans ; *Language ; Male ; Pitch Perception/*physiology ; Speech Perception/*physiology ; }, abstract = {Linguistic experience affects speech perception from early infancy, as previously evidenced by behavioral and brain measures. Current research focuses on whether linguistic effects on speech perception can be observed at an earlier stage in the neural processing of speech (i.e., auditory brainstem). Brainstem responses reflect rapid, automatic, and preattentive encoding of sounds. Positive experiential effects have been reported by examining the frequency-following response (FFR) component of the complex auditory brainstem response (cABR) in response to sustained high-energy periodic portions of speech sounds (vowels and lexical tones). The current study expands the existing literature by examining the cABR onset component in response to transient and low-energy portions of speech (consonants), employing simultaneous magnetoencephalography (MEG) in addition to electroencephalography (EEG), which provide complementary source information on cABR. Utilizing a cross-cultural design, we behaviorally measured perceptual responses to consonants in native Spanish- and English-speaking adults, in addition to cABR. Brain and behavioral relations were examined. Results replicated previous behavioral differences between language groups and further showed that individual consonant perception is strongly associated with EEG-cABR onset peak latency. MEG-cABR source analysis of the onset peaks complimented the EEG-cABR results by demonstrating subcortical sources for both peaks, with no group differences in peak locations. Current results demonstrate a brainstem-perception relation and show that the effects of linguistic experience on speech perception can be observed at the brainstem level.}, } @article {pmid30104355, year = {2018}, author = {Groopman, EE and Willingham, DG and Meshik, AP and Pravdivtseva, OV}, title = {Discovery of fissionogenic Cs and Ba capture five years after Oklo reactor shutdown.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8676-8681}, pmid = {30104355}, issn = {1091-6490}, abstract = {Understanding the release and sequestration of specific radioactive signatures into the environment is of extreme importance for long-term nuclear waste storage and reactor accident mitigation. Recent accidents at the Fukushima and Chernobyl nuclear reactors released radioactive 137Cs and 134Cs into the environment, the former of which is still live today. We have studied the migration of fission products in the Oklo natural nuclear reactor using an isotope imaging capability, the NAval Ultra-Trace Isotope Laboratory's Universal Spectrometer (NAUTILUS) at the US Naval Research Laboratory. In Oklo reactor zone (RZ) 13, we have identified the most depleted natural U of any known material with a 235U/238U ratio of 0.3655 ± 0.0007% (2σ). This sample contains the most extreme natural burnup in 149Sm, 151Eu, 155Gd, and 157Gd, which demonstrates that it was sourced from the most active Oklo reactor region. We have discovered that fissionogenic Cs and Ba were captured by Ru metal/sulfide aggregates shortly following reactor shutdown. Isochrons from the Ru aggregates place their closure time at 4.98 ± 0.56 y after the end of criticality. Most fissionogenic 135Ba and 137Ba in the Ru migrated and was incorporated as Cs over this period. Excesses in 134Ba in the Ru point to the burnup of 133Cs. Cesium and Ba were retained in the Ru despite local volcanic activity since the reactor shutdown and the high level of activity during reactor operation.}, } @article {pmid30104354, year = {2018}, author = {Wang, XJ and Chen, LH and Hofmann, AW and Hanyu, T and Kawabata, H and Zhong, Y and Xie, LW and Shi, JH and Miyazaki, T and Hirahara, Y and Takahashi, T and Senda, R and Chang, Q and Vaglarov, BS and Kimura, JI}, title = {Recycled ancient ghost carbonate in the Pitcairn mantle plume.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8682-8687}, pmid = {30104354}, issn = {1091-6490}, abstract = {The extreme Sr, Nd, Hf, and Pb isotopic compositions found in Pitcairn Island basalts have been labeled enriched mantle 1 (EM1), characterizing them as one of the isotopic mantle end members. The EM1 origin has been vigorously debated for over 25 years, with interpretations ranging from delaminated subcontinental lithosphere, to recycled lower continental crust, to recycled oceanic crust carrying ancient pelagic sediments, all of which may potentially generate the requisite radiogenic isotopic composition. Here we find that δ26Mg ratios in Pitcairn EM1 basalts are significantly lower than in normal mantle and are the lowest values so far recorded in oceanic basalts. A global survey of Mg isotopic compositions of potentially recycled components shows that marine carbonates constitute the most common and typical reservoir invariably characterized by extremely low δ26Mg values. We therefore infer that the subnormal δ26Mg of the Pitcairn EM1 component originates from subducted marine carbonates. This, combined with previously published evidence showing exceptionally unradiogenic Pb as well as sulfur isotopes affected by mass-independent fractionation, suggests that the Pitcairn EM1 component is most likely derived from late Archean subducted carbonate-bearing sediments. However, the low Ca/Al ratios of Pitcairn lavas are inconsistent with experimental evidence showing high Ca/Al ratios in melts derived from carbonate-bearing mantle sources. We suggest that carbonate-silicate reactions in the late Archean subducted sediments exhausted the carbonates, but the isotopically light magnesium of the carbonate was incorporated in the silicates, which then entered the lower mantle and ultimately became the Pitcairn plume source.}, } @article {pmid30104353, year = {2018}, author = {Heisser, RH and Patil, VP and Stoop, N and Villermaux, E and Dunkel, J}, title = {Controlling fracture cascades through twisting and quenching.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8665-8670}, pmid = {30104353}, issn = {1091-6490}, abstract = {Fracture fundamentally limits the structural stability of macroscopic and microscopic matter, from beams and bones to microtubules and nanotubes. Despite substantial recent experimental and theoretical progress, fracture control continues to present profound practical and theoretical challenges. While bending-induced fracture of elongated rod-like objects has been intensely studied, the effects of twist and quench dynamics have yet to be explored systematically. Here, we show how twist and quench protocols may be used to control such fracture processes, by revisiting Feynman's observation that dry spaghetti typically breaks into three or more pieces when exposed to large pure bending stresses. Combining theory and experiment, we demonstrate controlled binary fracture of brittle elastic rods for two distinct protocols based on twisting and nonadiabatic quenching. Our experimental data for twist-controlled fracture agree quantitatively with a theoretically predicted phase diagram, and we establish asymptotic scaling relations for quenched fracture. Due to their general character, these results are expected to apply to torsional and kinetic fracture processes in a wide range of systems.}, } @article {pmid30104352, year = {2018}, author = {George, RJ and Plog, S and Watson, AS and Schmidt, KL and Culleton, BJ and Harper, TK and Gilman, PA and LeBlanc, SA and Amato, G and Whiteley, P and Kistler, L and Kennett, DJ}, title = {Archaeogenomic evidence from the southwestern US points to a pre-Hispanic scarlet macaw breeding colony.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8740-8745}, pmid = {30104352}, issn = {1091-6490}, mesh = {Animals ; *Breeding ; *Fossils ; *Models, Biological ; Parrots/*physiology ; Phylogeography ; Southwestern United States ; }, abstract = {Hundreds of scarlet macaw (Ara macao cyanoptera) skeletons have been recovered from archaeological contexts in the southwestern United States and northwestern Mexico (SW/NW). The location of these skeletons, >1,000 km outside their Neotropical endemic range, has suggested a far-reaching pre-Hispanic acquisition network. Clear evidence for scarlet macaw breeding within this network is only known from the settlement of Paquimé in NW dating between 1250 and 1450 CE. Although some scholars have speculated on the probable existence of earlier breeding centers in the SW/NW region, there has been no supporting evidence. In this study, we performed an ancient DNA analysis of scarlet macaws recovered from archaeological sites in Chaco Canyon and the contemporaneous Mimbres area of New Mexico. All samples were directly radiocarbon dated between 900 and 1200 CE. We reconstructed complete or near-complete mitochondrial genome sequences of 14 scarlet macaws from five different sites. We observed remarkably low genetic diversity in this sample, consistent with breeding of a small founder population translocated outside their natural range. Phylogeographic comparisons of our ancient DNA mitogenomes with mitochondrial sequences from macaws collected during the last 200 years from their endemic Neotropical range identified genetic affinity between the ancient macaws and a single rare haplogroup (Haplo6) observed only among wild macaws in Mexico and northern Guatemala. Our results suggest that people at an undiscovered pre-Hispanic settlement dating between 900 and 1200 CE managed a macaw breeding colony outside their endemic range and distributed these symbolically important birds through the SW.}, } @article {pmid30104351, year = {2018}, author = {Brillada, C and Zheng, J and Krüger, F and Rovira-Diaz, E and Askani, JC and Schumacher, K and Rojas-Pierce, M}, title = {Phosphoinositides control the localization of HOPS subunit VPS41, which together with VPS33 mediates vacuole fusion in plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8305-E8314}, pmid = {30104351}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Membrane Fusion/*physiology ; Membrane Proteins/genetics/*metabolism ; Phosphatidylinositol Phosphates/genetics/metabolism ; Vacuoles/genetics/*metabolism ; Vesicular Transport Proteins/genetics/*metabolism ; }, abstract = {The vacuole is an essential organelle in plant cells, and its dynamic nature is important for plant growth and development. Homotypic membrane fusion is required for vacuole biogenesis, pollen germination, stomata opening, and gravity perception. Known components of the vacuole fusion machinery in eukaryotes include SNARE proteins, Rab GTPases, phosphoinositides, and the homotypic fusion and vacuolar protein sorting (HOPS) tethering complex. HOPS function is not well characterized in plants, but roles in embryogenesis and pollen tube elongation have been reported. Here, we show that Arabidopsis HOPS subunits VPS33 and VPS41 accumulate in late endosomes and that VPS41, but not VPS33, accumulates in the tonoplast via a wortmannin-sensitive process. VPS41 and VPS33 proteins bind to liposomes, but this binding is inhibited by phosphatidylinosiltol-3-phosphate [PtdIns(3)P] and PtdIns(3,5)P2, which implicates a nonconserved mechanism for HOPS recruitment in plants. Inducible knockdown of VPS41 resulted in dramatic vacuole fragmentation phenotypes and demonstrated a critical role for HOPS in vacuole fusion. Furthermore, we provide evidence for genetic interactions between VPS41 and VTI11 SNARE that regulate vacuole fusion, and the requirement of a functional SNARE complex for normal VPS41 and VPS33 localization. Finally, we provide evidence to support VPS33 and SYP22 at the initial stage for HOPS-SNARE interactions, which is similar to other eukaryotes. These results highlight both conserved and specific mechanisms for HOPS recruitment and function during vacuole fusion in plants.}, } @article {pmid30104350, year = {2018}, author = {Obradovich, N and Tingley, D and Rahwan, I}, title = {Effects of environmental stressors on daily governance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8710-8715}, pmid = {30104350}, issn = {1091-6490}, mesh = {*Accidents, Traffic ; *Climate Change ; *Emergency Medical Dispatch ; Environmental Exposure/*adverse effects ; Female ; *Food Safety ; Humans ; Male ; *Models, Theoretical ; Stress, Psychological/*epidemiology ; United States ; }, abstract = {Human workers ensure the functioning of governments around the world. The efficacy of human workers, in turn, is linked to the climatic conditions they face. Here we show that the same weather that amplifies human health hazards also reduces street-level government workers' oversight of these hazards. To do so, we employ US data from over 70 million regulatory police stops between 2000 and 2017, from over 500,000 fatal vehicular crashes between 2001 and 2015, and from nearly 13 million food safety violations across over 4 million inspections between 2012 and 2016. We find that cold and hot temperatures increase fatal crash risk and incidence of food safety violations while also decreasing police stops and food safety inspections. Added precipitation increases fatal crash risk while also decreasing police stops. We examine downscaled general circulation model output to highlight the possible day-to-day governance impacts of climate change by 2050 and 2099. Future warming may augment regulatory oversight during cooler seasons. During hotter seasons, however, warming may diminish regulatory oversight while simultaneously amplifying the hazards government workers are tasked with overseeing.}, } @article {pmid30104349, year = {2018}, author = {Strona, G and Stringer, SD and Vieilledent, G and Szantoi, Z and Garcia-Ulloa, J and A Wich, S}, title = {Small room for compromise between oil palm cultivation and primate conservation in Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8811-8816}, pmid = {30104349}, issn = {1091-6490}, mesh = {Africa ; Animals ; Arecaceae/*growth & development ; *Biodiversity ; *Conservation of Natural Resources ; Crops, Agricultural/*growth & development ; Primates/*physiology ; }, abstract = {Despite growing awareness about its detrimental effects on tropical biodiversity, land conversion to oil palm continues to increase rapidly as a consequence of global demand, profitability, and the income opportunity it offers to producing countries. Although most industrial oil palm plantations are located in Southeast Asia, it is argued that much of their future expansion will occur in Africa. We assessed how this could affect the continent's primates by combining information on oil palm suitability and current land use with primate distribution, diversity, and vulnerability. We also quantified the potential impact of large-scale oil palm cultivation on primates in terms of range loss under different expansion scenarios taking into account future demand, oil palm suitability, human accessibility, carbon stock, and primate vulnerability. We found a high overlap between areas of high oil palm suitability and areas of high conservation priority for primates. Overall, we found only a few small areas where oil palm could be cultivated in Africa with a low impact on primates (3.3 Mha, including all areas suitable for oil palm). These results warn that, consistent with the dramatic effects of palm oil cultivation on biodiversity in Southeast Asia, reconciling a large-scale development of oil palm in Africa with primate conservation will be a great challenge.}, } @article {pmid30104348, year = {2018}, author = {Ruan, Z and Kannan, N}, title = {Altered conformational landscape and dimerization dependency underpins the activation of EGFR by αC-β4 loop insertion mutations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8162-E8171}, pmid = {30104348}, issn = {1091-6490}, support = {R01 GM114409/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; CHO Cells ; Cricetulus ; ErbB Receptors/antagonists & inhibitors/*chemistry/genetics ; Humans ; *Molecular Dynamics Simulation ; *Mutagenesis, Insertional ; Protein Kinase Inhibitors/*chemistry ; *Protein Multimerization ; Protein Structure, Secondary ; }, abstract = {Mutational activation of epidermal growth factor receptor (EGFR) in human cancers involves both point mutations and complex mutations (insertions and deletions). In particular, short in-frame insertion mutations within a conserved αC-β4 loop in the EGFR kinase domain are frequently observed in tumor samples and patients harboring these mutations are insensitive to first-generation EGFR inhibitors. Despite the prevalence and clinical relevance of insertion mutations, the mechanisms by which these mutations regulate EGFR activity and contribute to drug sensitivity are poorly understood. Using cell-based mutation screening, we find that the precise location, length, and sequence of the inserted segment are critical for ligand-independent EGFR activation and downstream signaling. We identify three insertion mutations (N771_P772insN, D770_N771insG, and D770>GY) that activate EGFR in a unique way by relying more on the "acceptor" interface for kinase activation. Our drug inhibition studies indicate that these activating insertion mutations respond more favorably to osimertinib, a recently Food and Drug Administration-approved EGFR inhibitor for T790M-positive patients with lung cancer. Molecular dynamics simulations and umbrella sampling of WT and mutant EGFR suggest a model in which activating insertion mutations increase catalytic activity by relieving key autoinhibitory interactions associated with αC-helix movement and by lowering the transition free energy ([Formula: see text]) between active and inactive states. Our studies also identify a transition state sampled by activating insertion mutations that can be exploited in the design of mutant-selective EGFR inhibitors.}, } @article {pmid30104347, year = {2018}, author = {Yoshida, K and Hara, A and Sugiura, K and Fukaya, Y and Hisabori, T}, title = {Thioredoxin-like2/2-Cys peroxiredoxin redox cascade supports oxidative thiol modulation in chloroplasts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8296-E8304}, pmid = {30104347}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Carrier Proteins/genetics/*metabolism ; Chloroplast Proteins/genetics/*metabolism ; Chloroplasts/genetics/*metabolism ; Oxidation-Reduction ; Peroxiredoxins/genetics/*metabolism ; Sulfhydryl Compounds/*metabolism ; }, abstract = {Thiol-based redox regulation is central to adjusting chloroplast functions under varying light conditions. A redox cascade via the ferredoxin-thioredoxin reductase (FTR)/thioredoxin (Trx) pathway has been well recognized to mediate the light-responsive reductive control of target proteins; however, the molecular basis for reoxidizing its targets in the dark remains unidentified. Here, we report a mechanism of oxidative thiol modulation in chloroplasts. We biochemically characterized a chloroplast stroma-localized atypical Trx from Arabidopsis, designated as Trx-like2 (TrxL2). TrxL2 had redox-active properties with an unusually less negative redox potential. By an affinity chromatography-based method, TrxL2 was shown to interact with a range of chloroplast redox-regulated proteins. The direct discrimination of thiol status indicated that TrxL2 can efficiently oxidize, but not reduce, these proteins. A notable exception was found in 2-Cys peroxiredoxin (2CP); TrxL2 was able to reduce 2CP with high efficiency. We achieved a complete in vitro reconstitution of the TrxL2/2CP redox cascade for oxidizing redox-regulated proteins and draining reducing power to hydrogen peroxide (H2O2). We further addressed the physiological relevance of this system by analyzing protein-oxidation dynamics. In Arabidopsis plants, a decreased level of 2CP led to the impairment of the reoxidation of redox-regulated proteins during light-dark transitions. A delayed response of protein reoxidation was concomitant with the prolonged accumulation of reducing power in TrxL2. These results suggest an in vivo function of the TrxL2/2CP redox cascade for driving oxidative thiol modulation in chloroplasts.}, } @article {pmid30104346, year = {2018}, author = {Zhu, M and Zhao, H and Limbo, O and Russell, P}, title = {Mre11 complex links sister chromatids to promote repair of a collapsed replication fork.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8793-8798}, pmid = {30104346}, issn = {1091-6490}, support = {R01 CA077325/CA/NCI NIH HHS/United States ; R01 CA117638/CA/NCI NIH HHS/United States ; R01 GM059447/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromatids/genetics/*metabolism ; Chromosomes, Fungal/genetics/*metabolism ; DNA Repair/*physiology ; DNA Replication/physiology ; DNA, Fungal/genetics/*metabolism ; DNA-Binding Proteins/genetics/metabolism ; Exodeoxyribonucleases/genetics/*metabolism ; Multiprotein Complexes/genetics/*metabolism ; Mutation ; Schizosaccharomyces/genetics/*metabolism ; Schizosaccharomyces pombe Proteins/genetics/*metabolism ; }, abstract = {Collapsed replication forks, which are a major source of DNA double-strand breaks (DSBs), are repaired by sister chromatid recombination (SCR). The Mre11-Rad50-Nbs1 (MRN) protein complex, assisted by CtIP/Sae2/Ctp1, initiates SCR by nucleolytically resecting the single-ended DSB (seDSB) at the collapsed fork. The molecular architecture of the MRN intercomplex, in which zinc hooks at the apices of long Rad50 coiled-coils connect two Mre112-Rad502 complexes, suggests that MRN also structurally assists SCR. Here, Rad50 ChIP assays in Schizosaccharomyces pombe show that MRN sequentially localizes with the seDSB and sister chromatid at a collapsed replication fork. Ctp1, which has multivalent DNA-binding and DNA-bridging activities, has the same DNA interaction pattern. Provision of an intrachromosomal repair template alleviates the nonnucleolytic requirement for MRN to repair the broken fork. Mutations of zinc-coordinating cysteines in the Rad50 hook severely impair SCR. These data suggest that the MRN complex facilitates SCR by linking the seDSB and sister chromatid.}, } @article {pmid30104345, year = {2018}, author = {Haraguchi, S and Shingae, T and Fujisawa, T and Kasai, N and Kumauchi, M and Hanamoto, T and Hoff, WD and Unno, M}, title = {Spectroscopic ruler for measuring active-site distortions based on Raman optical activity of a hydrogen out-of-plane vibration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8671-8675}, pmid = {30104345}, issn = {1091-6490}, mesh = {Bacterial Proteins/*chemistry ; Halorhodospira halophila/*chemistry ; Hydrogen/*chemistry ; *Models, Molecular ; Photoreceptors, Microbial/*chemistry ; Quantum Theory ; Spectrum Analysis, Raman/*methods ; }, abstract = {Photoactive yellow protein (PYP), from the phototrophic bacterium Halorhodospira halophila, is a small water-soluble photoreceptor protein and contains p-coumaric acid (pCA) as a chromophore. PYP has been an attractive model for studying the physical chemistry of protein active sites. Here, we explore how Raman optical activity (ROA) can be used to extract quantitative information on distortions of the pCA chromophore at the active site in PYP. We use 13C8-pCA to assign an intense signal at 826 cm-1 in the ROA spectrum of PYP to a hydrogen out-of-plane vibration of the ethylenic moiety of the chromophore. Quantum-chemical calculations based on density functional theory demonstrate that the sign of this ROA band reports the direction of the distortion in the dihedral angle about the ethylenic C=C bond, while its amplitude is proportional to the dihedral angle. These results document the ability of ROA to quantify structural deformations of a cofactor molecule embedded in a protein moiety.}, } @article {pmid30104137, year = {2018}, author = {Bernot, RJ and Poulin, R}, title = {Ecological Stoichiometry for Parasitologists.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {928-933}, doi = {10.1016/j.pt.2018.07.008}, pmid = {30104137}, issn = {1471-5007}, abstract = {Ecological stoichiometry (ES) is an ecological theory used to study the imbalances of chemical elements, ratios, and flux rates among organisms and the environment to better understand nutrient cycling, energy flow, and the role of organisms in ecosystems. Parasitologists can use this framework to study phenomena across biological scales from genomes to ecosystems. By using the common currency of elemental ratios such as carbon:nitrogen:phosphorus, parasitologists are beginning to explicitly link parasite-host interactions to ecosystem dynamics. Thus, ecological stoichiometry provides a framework for studying the feedbacks of parasites on the environment as well as the effects of the environment on parasites and disease.}, } @article {pmid30103831, year = {2018}, author = {Noeske, J and Yakam, AN and Foe, JLA and Nguafack, D and Kuaban, C}, title = {Rifampicin resistance in new bacteriologically confirmed pulmonary tuberculosis patients in Cameroon: a cross-sectional survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {580}, pmid = {30103831}, issn = {1756-0500}, mesh = {Adolescent ; Antitubercular Agents/*pharmacology ; Cameroon ; Cross-Sectional Studies ; Female ; Humans ; Male ; Mycobacterium tuberculosis ; Rifampin/*pharmacology ; Surveys and Questionnaires ; *Tuberculosis, Multidrug-Resistant ; Tuberculosis, Pulmonary/*drug therapy ; Young Adult ; }, abstract = {OBJECTIVE: In Cameroon, tuberculosis (TB) cases are diagnosed and treated within a nationwide network of 248 diagnostic and treatment centres. In 2016, the centers notified a total of 175 multidrug-resistant (MDR-)TB cases, most of them retreatment cases. According to the WHO, the expected number of MDR-TB cases was estimated to be 1200 (1000-2200) corresponding to a rate of 6.8 (4.3-9.4) per 100,000 population. This indicates a notification gap of more than 80%. The objective of this study was to estimate the prevalence of MDR-TB in new bacteriologically confirmed pulmonary TB cases. We undertook a nationwide cross sectional survey during 6 weeks.

RESULTS: During the study period, the NTP notified 1478 new bacteriologically confirmed pulmonary TB cases. Among them, 1029 (70%) had a valid Xpert result and 16 were identified with rifampicin resistant (RR-TB), a tracer of MDR-TB. This gives a prevalence of 1.6% (95% CI 0.8-2.3) among incident cases. The rate of RR-TB in the regions varied between 0 and 3.3%. If the results of this study are confirmed, the incidence rate given by WHO (2.8%, 95% CI 2.1-3.4) might be an over-estimation.}, } @article {pmid30103830, year = {2018}, author = {Kawata, S and Saito, E}, title = {An exploratory pilot study on health education program to improve health literacy among female in their 20s.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {572}, pmid = {30103830}, issn = {1756-0500}, support = {15K20801//Japan Society for the Promotion of Science/ ; }, mesh = {Adult ; Female ; *Health Education ; Health Knowledge, Attitudes, Practice ; *Health Literacy ; Humans ; Japan ; Pilot Projects ; Retrospective Studies ; Uterine Cervical Neoplasms/*diagnosis/prevention & control ; Young Adult ; }, abstract = {OBJECTIVE: Health literacy (HL) is one of the most important concepts in women's healthcare. The low cervical cancer screening rate for young Japanese women is an urgent issue. Cervical cancer is preventable, and cervical cancer screening behavior is associated with HL. Therefore, the present study aimed to elucidate the effects of a health education program to improve HL among young female undergraduate students in Japan. Immediately after completing the program, participants evaluated their level of satisfaction with and the level of difficulty of the program, their understanding of the educational materials, and the length of the curriculum. Furthermore, 1 month after completing the program, participants evaluated their overall HL and their knowledge of women's health, and indicated whether they had undergone cervical cancer screening.

RESULTS: Thirteen female undergraduate students in their 20s participated. All participants indicated high levels of satisfaction and understanding of the material, and an appropriate level of difficulty of the curriculum. Three participants indicated that the program was too long. All participants had improved HL and knowledge of women's health after completing the education program, but no significant difference was observed in the cervical cancer screening rate. Trial registration UMINR000036690 April 10, 2018 retrospectively registered.}, } @article {pmid30103824, year = {2018}, author = {Teka, TT and Feyissa, TR and Melka, AS and Bobo, FT}, title = {Role of antenatal and postnatal care in contraceptive use during postpartum period in western Ethiopia: a cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {581}, pmid = {30103824}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; *Contraception Behavior ; Contraceptive Agents ; Cross-Sectional Studies ; Ethiopia ; *Family Planning Services ; Female ; Humans ; Infant ; Middle Aged ; *Postnatal Care ; Postpartum Period ; Pregnancy ; Reproducibility of Results ; Young Adult ; }, abstract = {OBJECTIVE: Little has been known about the magnitude and predictors of contraceptive use in extended postpartum period in Ethiopia. Thus, this study aims to assess the magnitude and determinants of contraception utilization in extended postpartum period. A community based cross-sectional survey was conducted in Gida Ayana district, Oromia regional state, Ethiopia in February 2015. Six hundred and three postpartum women were included using a multistage sampling technique. Descriptive statistics were used to summarize the data and logistic regressions were used to assess the predictors of modern family planning use at 95% confidence interval.

RESULTS: The proportion of women using any of the modern family planning in extended postpartum period was 45.4%. Women who had four and more antenatal care visits (AOR = 2.93; 95% CI 1.08-7.94), mothers who received post-natal care (AOR = 4.34; 95% CI 2.37-7.94), and those desiring less number of children (AOR = 5; 95% CI 2.19-11.41) were more likely to use modern family planning methods during the extended postpartum period. Therefore, health care providers should work to improve quality of health services provided during antenatal care and postnatal care to enhance family planning utilization among post-partum women.}, } @article {pmid30103821, year = {2018}, author = {Yonekura, S and Itoh, M and Shiratori, E and Ohtaka, M and Tohda, S}, title = {FOXP3 knockdown inhibits the proliferation and reduces NOTCH1 expression of T cell acute lymphoblastic leukemia cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {582}, pmid = {30103821}, issn = {1756-0500}, support = {26460669//a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science/ ; }, mesh = {*Cell Proliferation ; Forkhead Transcription Factors/genetics/*physiology ; Gene Knockdown Techniques ; Humans ; *Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Receptor, Notch1/*metabolism ; T-Lymphocytes ; }, abstract = {OBJECTIVE: Forkhead box P3 (FOXP3) is a master transcriptional factor of regulatory T-cells (Tregs). Recent studies have shown that FOXP3 is associated with growth inhibition of cancer cells. However, the role of FOXP3 in acute T-lymphoblastic leukemia (T-ALL) cells is not known. It was also reported that NOTCH signaling promoted the expression of FOXP3 in Tregs. However, the effect of FOXP3 on NOTCH expression in T-ALL cells is little known. Therefore, we examined the effect of FOXP3 knockdown on the proliferation of T-ALL cells and NOTCH1 signaling.

RESULTS: Two T-ALL cell lines Jurkat and KOPT-K1, harboring activating NOTCH1 mutations, were transfected with small interfering RNA against FOXP3. Cell growth was assessed with a colorimetric assay and morphology was observed under a microscope. FOXP3 knockdown significantly reduced cell growth and induced morphological changes suggesting apoptosis. Quantitative polymerase chain reaction revealed that FOXP3 knockdown caused the downregulation of mRNA expression of NOTCH1 and HES1. These findings suggest that FOXP3 supports the growth of T-ALL cells although this can not be generalized because we examined only two cell lines. The observed growth suppression can be partly due to the downregulation of NOTCH1 signaling. FOXP3 may be a potential therapeutic target in T-ALL.}, } @article {pmid30103819, year = {2018}, author = {Lourenço, KS and Suleiman, AKA and Pijl, A and van Veen, JA and Cantarella, H and Kuramae, EE}, title = {Resilience of the resident soil microbiome to organic and inorganic amendment disturbances and to temporary bacterial invasion.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {142}, pmid = {30103819}, issn = {2049-2618}, mesh = {Bacteria/classification/drug effects/*growth & development/isolation & purification ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Metagenomics ; Nitrogen/adverse effects ; RNA, Ribosomal, 16S/genetics ; Recycling/methods ; Saccharum/chemistry/*growth & development ; Soil Microbiology ; Solid Waste/*adverse effects ; }, abstract = {BACKGROUND: Vinasse, a by-product of sugarcane ethanol production, is recycled by sugarcane plantations as a fertilizer due to its rich nutrient content. However, the impacts of the chemical and microbial composition of vinasse on soil microbiome dynamics are unknown. Here, we evaluate the recovery of the native soil microbiome after multiple disturbances caused by the application of organic vinasse residue, inorganic nitrogen, or a combination of both during the sugarcane crop-growing season (389 days). Additionally, we evaluated the resistance of the resident soil microbial community to the vinasse microbiome.

RESULTS: Vinasse applied alone or 30 days prior to N resulted in similar changes in the soil microbial community. Furthermore, the impact of the application of vinasse together with N fertilizer on the soil microbial community differed from that of N fertilizer alone. Organic vinasse is a source of microbes, nutrients, and organic matter, and the combination of these factors drove the changes in the resident soil microbial community. However, these changes were restricted to a short period of time due to the capacity of the soil community to recover. The invasive bacteria present in the vinasse microbiome were unable to survive in the soil conditions and disappeared after 31 days, with the exception of the Acetobacteraceae (native in the soil) and Lactobacillaceae families.

CONCLUSION: Our analysis showed that the resident soil microbial community was not resistant to vinasse and inorganic N application but was highly resilient.}, } @article {pmid30103818, year = {2018}, author = {Semachew Kasa, A and Tarekegn, M and Embiale, N}, title = {Knowledge, attitude and practice towards family planning among reproductive age women in a resource limited settings of Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {577}, pmid = {30103818}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Ethiopia ; *Family Planning Services ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: To assess the knowledge and attitude regarding family planning and the practice of family planning among the women of reproductive age group in South Achefer District, Northwest Ethiopia, 2017.

RESULT: The study showed that the overall proper knowledge, attitude and practice of women towards family planning (FP) was 42.3%, 58.8%, and 50.4% respectively. Factors associated with the practice of FP were: residence, marital status, educational status, age, occupation, and knowledge, and attitude, number of children and monthly average household income of participants. In this study, the level of knowledge and attitude towards family planning was relatively low and the level of family planning utilization was quite low in comparison with many studies. Every health worker should teach the community on family planning holistically to increase the awareness so that family planning utilization will be enhanced. Besides, more studies are needed in a thorough investigation of the different reasons affecting the non-utilizing of family planning and how these can be addressed are necessary.}, } @article {pmid30103816, year = {2018}, author = {Norling, M and Jareborg, N and Dainat, J}, title = {EMBLmyGFF3: a converter facilitating genome annotation submission to European Nucleotide Archive.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {584}, pmid = {30103816}, issn = {1756-0500}, mesh = {*Databases, Nucleic Acid ; Europe ; Genome ; Internet ; *Molecular Sequence Annotation ; *Nucleotides ; Software ; }, abstract = {OBJECTIVE: The state-of-the-art genome annotation tools output GFF3 format files, while this format is not accepted as submission format by the International Nucleotide Sequence Database Collaboration (INSDC) databases. Converting the GFF3 format to a format accepted by one of the three INSDC databases is a key step in the achievement of genome annotation projects. However, the flexibility existing in the GFF3 format makes this conversion task difficult to perform. Until now, no converter is able to handle any GFF3 flavour regardless of source.

RESULTS: Here we present EMBLmyGFF3, a robust universal converter from GFF3 format to EMBL format compatible with genome annotation submission to the European Nucleotide Archive. The tool uses json parameter files, which can be easily tuned by the user, allowing the mapping of corresponding vocabulary between the GFF3 format and the EMBL format. We demonstrate the conversion of GFF3 annotation files from four different commonly used annotation tools: Maker, Prokka, Augustus and Eugene. EMBLmyGFF3 is freely available at https://github.com/NBISweden/EMBLmyGFF3 .}, } @article {pmid30103813, year = {2018}, author = {Alemu, MB and Asnake, MA and Lemma, MY and Melak, MF and Yenit, MK}, title = {Utilization of insecticide treated bed net and associated factors among households of Kola Diba town, North Gondar, Amhara region, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {575}, pmid = {30103813}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Ethiopia ; Family Characteristics ; Female ; Humans ; Insecticide-Treated Bednets/*statistics & numerical data ; Malaria/*prevention & control ; Male ; Middle Aged ; Young Adult ; }, abstract = {OBJECTIVE: The primary aim of this study was to assess the utilization of an insecticide-treated bed net on the preceding night and associated factors among households of Kola Diba town in 2017.

RESULTS: Of the 260 households, 239 (91.9%) (95% CI = 88.5-95%) utilized insecticide-treated bed net on the night preceding the interview. 242 (93.1%) households didn't treat the bed net whereas 18 (6.9%) treat the bed net by chemical regularly. Household structure and knowledge about malaria transmission were found to be associated with insecticide-treated bed net utilization.}, } @article {pmid30103812, year = {2018}, author = {Tomita, D and Suga, T and Tanaka, T and Ueno, H and Miyake, Y and Otsuka, M and Nagano, A and Isaka, T}, title = {A pilot study on the importance of forefoot bone length in male 400-m sprinters: is there a key morphological factor for superior long sprint performance?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {583}, pmid = {30103812}, issn = {1756-0500}, mesh = {Anthropometry ; *Athletic Performance ; Biomechanical Phenomena ; Foot/*anatomy & histology ; Humans ; Male ; Pilot Projects ; *Running ; Switzerland ; Young Adult ; }, abstract = {OBJECTIVE: The main purpose of the present study was to determine the relationship between the forefoot bone length and long sprint performance in well-trained 400-m specialized sprinters. The total lengths of the forefoot bones of the big and second toes in 25 male 400-m sprinters and 25 male non-sprinters were measured using magnetic resonance imaging. The forefoot bones of each toe were totaled to assess overall forefoot bone length and then normalized to the maximum foot length.

RESULTS: The relative total lengths of the forefoot bones in the big and second toes were significantly longer in 400-m sprinters than in non-sprinters (P < 0.05 for both). The relative total length of the forefoot bones of the second toe, but not of the big toe, in 400-m sprinters was significantly correlated with personal best 400-m sprint time (r = - 0.441, P = 0.028). These findings demonstrated that longer forefoot bones are related to higher long sprint performance in well-trained 400-m specialized sprinters. Therefore, the present study is the first to determine that morphological factors such as long forefoot bones may play an important role in achieving superior long sprinting performance.}, } @article {pmid30103809, year = {2018}, author = {Budachetri, K and Kumar, D and Crispell, G and Beck, C and Dasch, G and Karim, S}, title = {The tick endosymbiont Candidatus Midichloria mitochondrii and selenoproteins are essential for the growth of Rickettsia parkeri in the Gulf Coast tick vector.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {141}, pmid = {30103809}, issn = {2049-2618}, support = {P20 RR016476/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Arachnid Vectors/genetics/metabolism/microbiology ; Arthropod Proteins/genetics/metabolism ; Female ; Gene Expression Regulation, Bacterial ; Gene Silencing ; Gulf of Mexico ; Male ; Oxidative Stress ; Rickettsia/*growth & development ; Rickettsiaceae/*physiology ; Selenoproteins/*genetics/metabolism ; Symbiosis ; Ticks/genetics/metabolism/*microbiology ; Up-Regulation ; }, abstract = {BACKGROUND: Pathogen colonization inside tick tissues is a significant aspect of the overall competence of a vector. Amblyomma maculatum is a competent vector of the spotted fever group rickettsiae, Rickettsia parkeri. When R. parkeri colonizes its tick host, it has the opportunity to dynamically interact with not just its host but with the endosymbionts living within it, and this enables it to modulate the tick's defenses by regulating tick gene expression. The microbiome in A. maculatum is dominated by two endosymbiont microbes: a Francisella-like endosymbiont (FLE) and Candidatus Midichloria mitochondrii (CMM). A range of selenium-containing proteins (selenoproteins) in A. maculatum ticks protects them from oxidative stress during blood feeding and pathogen infections. Here, we investigated rickettsial multiplication in the presence of tick endosymbionts and characterized the functional significance of selenoproteins during R. parkeri replication in the tick.

RESULTS: FLE and CMM were quantified throughout the tick life stages by quantitative PCR in R. parkeri-infected and uninfected ticks. R. parkeri infection was found to decrease the FLE numbers but CMM thrived across the tick life cycle. Our qRT-PCR analysis indicated that the transcripts of genes with functions related to redox (selenogenes) were upregulated in ticks infected with R. parkeri. Three differentially expressed proteins, selenoprotein M, selenoprotein O, and selenoprotein S were silenced to examine their functional significance during rickettsial replication within the tick tissues. Gene silencing of the target genes was found to impair R. parkeri colonization in the tick vector. Knockdown of the selenogenes triggered a compensatory response from other selenogenes, as observed by changes in gene expression, but oxidative stress levels and endoplasmic reticulum stress inside the ticks were also found to have heightened.

CONCLUSIONS: This study illustrates the potential of this new research model for augmenting our understanding of the pathogen interactions occurring within tick hosts and the important roles that symbionts and various tick factors play in regulating pathogen growth.}, } @article {pmid30103808, year = {2018}, author = {Loupa, CV and Meimeti, E and Voyatzoglou, E and Donou, A and Koutsantoniou, E and Lafoyanni, S}, title = {Successful nonsurgical therapy of a diabetic foot osteomyelitis in a patient with peripheral artery disease with almost complete radiological restoration.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {579}, pmid = {30103808}, issn = {1756-0500}, mesh = {Aged ; *Angioplasty ; Anti-Bacterial Agents/*therapeutic use ; Diabetic Foot/*complications ; Greece ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus ; Osteomyelitis/etiology/*therapy ; Peripheral Arterial Disease ; }, abstract = {BACKGROUND: Diabetic foot ulcer (DFU) is a common complication in patients with diabetes mellitus (DM) and can consequently lead to soft tissue infection and osteomyelitis.

CASE PRESENTATION: We present a case of a 68-year-old man with a history of Type 2 DM and symptomatic peripheral artery disease, referred to our hospital due to an infected lower extremity DFU. Cultures revealed methicillin-resistant Staphylococcus aureus and Stenotrophomonas maltophilia. There was a significant increase of inflammatory marker levels and plain X-rays revealed osteomyelitis. He underwent lower extremity angioplasty for the restoration of the blood flow. He received targeted intravenous antibiotic therapy for 2 weeks and continued ciprofloxacin along with clindamycin per os for 10 more weeks as outpatient.

CONCLUSION: As a result, the patient presented almost complete healing of his DFU, reconstruction of osteomyelitis defects in X-ray and complete restoration of his foot functionality only 4 months after the end of the treatment. This case demonstrates a DFU complicated by osteomyelitis which resolved medically and nonsurgically, with the exception of surgical restoration of the blood flow.}, } @article {pmid30103806, year = {2018}, author = {Teklay, G and Teshale, T and Tasew, H and Mariye, T and Berihu, H and Zeru, T}, title = {Risk factors of preterm birth among mothers who gave birth in public hospitals of central zone, Tigray, Ethiopia: unmatched case-control study 2017/2018.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {571}, pmid = {30103806}, issn = {1756-0500}, support = {AKU0001/2010//Aksum University/ ; }, mesh = {Adult ; Case-Control Studies ; Ethiopia ; Female ; Hospitals, Public/*statistics & numerical data ; Humans ; Infant, Newborn ; Mothers ; Pregnancy ; Premature Birth/*epidemiology ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: The aim of the study was to identify the risk factors for preterm birth in public hospitals of the central zone, Tigray, Ethiopia 2017/2018.

RESULT: A total of 88 neonates who born preterm (cases) and 176 neonates who born term (controls) with their index mothers were included making a response rate of 100%. About 84/88 (95.5%) mothers in cases and 173/176 (98.3%) in control had antenatal care follow up. Among them, 33 (39.3%) cases and 102 (58%) controls were had antenatal care follow up four times and above. In multiple logistic regression at P-value < 0.05, mothers with ANC follow up less than four [AOR 95% CI 2.15 (1.19, 3.85)], mothers with pregnancy-induced hypertension [AOR 3.245; 95% CI (1.58, 6.67)], multiple pregnancy [AOR 2.47; 95% CI (1.14, 5.33)], fetal distress [AOR 4.0; 95% CI (1.9, 8.2)] and birth defect [AOR 3.19; 95% CI (1.22, 8.34)] were independent risk factors of preterm delivery.}, } @article {pmid30103805, year = {2018}, author = {Asim, M and Mudassir, G and Hashmi, AA and Abid, M and Sheikh, AK and Naveed, H and Habib, M and Edhi, MM and Khan, A}, title = {Diagnostic accuracy of fine needle aspiration biopsy in pediatric small round cell tumors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {573}, pmid = {30103805}, issn = {1756-0500}, mesh = {Adolescent ; *Biopsy, Fine-Needle ; Child ; Child, Preschool ; Female ; Humans ; Immunohistochemistry ; Infant ; Infant, Newborn ; Lymphoma, Non-Hodgkin/*diagnosis ; Male ; Pakistan ; Sensitivity and Specificity ; Wilms Tumor/*diagnosis ; }, abstract = {OBJECTIVE: Fine needle aspiration biospy (FNAB) is a simple, cost effective procedure, which can be carried out in the out-patient department. The objective of our study was to determine the diagnostic accuracy of fine needle aspiration biopsy in small round cell tumors of childhood, keeping histopathology as the gold standard.

RESULTS: Out of these 50 cases, 35 (70%) were small round cell tumors and 15 (30%) cases of other childhood malignancies and certain reactive conditions. In our study, the most common malignant small round cell tumor (SRCT) on histopathology was Wilms tumor (10 cases) followed by non Hodgkin lymphoma (9 cases). FNAB results were correlated with the histological findings and the diagnostic accuracy of SRCT came out to be 98%. The sensitivity and specificity of FNAB in diagnosing SRCT was 97% and 100% respectively. FNAB was found to be a very useful technique in the initial evaluation of any palpable lesion of childhood. Although the small round cell tumors appear cytologically similar, in the hands of experienced cytopathologists, the subtle morphological features can help towards the final diagnosis. In addition, clinical and radiological findings are invaluable assets, which help to reach the final diagnosis.}, } @article {pmid30103802, year = {2018}, author = {Hashmi, AA and Mahboob, R and Khan, SM and Irfan, M and Nisar, M and Iftikhar, N and Siddiqui, M and Faridi, N and Khan, A and Edhi, MM}, title = {Clinical and prognostic profile of Her2neu positive (non-luminal) intrinsic breast cancer subtype: comparison with Her2neu positive luminal breast cancers.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {574}, pmid = {30103802}, issn = {1756-0500}, mesh = {Adult ; Biomarkers, Tumor/*analysis ; Breast Neoplasms/*diagnosis ; Female ; Humans ; Ki-67 Antigen/analysis ; Middle Aged ; Prognosis ; Receptor, ErbB-2/*analysis ; Receptors, Estrogen ; Receptors, Progesterone ; }, abstract = {OBJECTIVE: Her2neu receptor is proto-oncogene which can be over-expressed in both luminal and non-luminal breast cancers. In the present study, we aimed to compare the prognostic and predictive factors like tumor grade, T-stage, N-stage and ki67 index in Her2neu intrinsic breast cancer subtype with Her2neu over-expressed luminal breast cancers.

RESULTS: 801 (41%) cases were Her2neu positive; out of which, 418 cases (52.2%) showed ER positivity and thus were classified as Her2neu positive luminal cancers whereas 383 cases (47.8%) were ER and PR negative and therefore were labeled as intrinsic Her2neu subtype (non-luminal). Her2neu positive (non-luminal) cancers were significantly associated with higher grades and Ki67 proliferative index compared to Her2neu positive luminal cancers. On the other no significant association was noted in T-stage and N-stage. We found a high frequency of her2neu positivity in our studied population of breast cancer. Moreover, association of her2neu positive (non-luminal) breast cancers with higher grade and ki67 index indicates a predictive value of ER/PR positivity in her2neu positive breast cancers. On the other hand, lack of association with respect to T and N stage, signifies no prognostic benefit of ER/PR in her2neu positive breast cancers.}, } @article {pmid30103801, year = {2018}, author = {Mavoa, S and Lamb, K and O'Sullivan, D and Witten, K and Smith, M}, title = {Are disadvantaged children more likely to be excluded from analysis when applying global positioning systems inclusion criteria?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {578}, pmid = {30103801}, issn = {1756-0500}, mesh = {Adolescent ; Child ; *Environmental Exposure ; Female ; *Geographic Information Systems ; Humans ; Male ; New Zealand ; Schools ; Taiwan ; *Vulnerable Populations ; }, abstract = {OBJECTIVE: When using global positioning systems (GPS) to assess an individual's exposure to their environment, a first step in data cleaning is to establish minimum GPS 'inclusion criteria' (a set of rules used to determine which GPS data are able to be included in analyses). Care is needed at this stage to avoid any data exclusion (data loss) systematically biasing results in terms of characteristics of the environment and participants. The extent of potential systematic bias in sample retention due to GPS data loss and application of GPS inclusion criteria is unknown. The aim of this study was to describe differences in sample size and socio-demographic characteristics of the retained sample when applying three different GPS inclusion criteria. The study assessed 7-day GPS data collected from children (aged 9-13 years) recruited from nine schools in Auckland, New Zealand as part of the Kids in the City study.

RESULTS: Participants from ethnic minorities and those attending schools in lower socioeconomic areas were disproportionately excluded from the retained samples. This highlights potential equity implications in basing the assessment of exposure-which ultimately influences research results on the relationship between environment and health-on non-representative GPS data.}, } @article {pmid30103799, year = {2018}, author = {Gebremedhin, G and Tetemke, D and Gebremedhin, M and Kahsay, G and Zelalem, H and Syum, H and Gerensea, H}, title = {Factors associated with latrine utilization among model and non-model families in Laelai Maichew Woreda, Aksum, Tigray, Ethiopia: comparative community based study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {586}, pmid = {30103799}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Ethiopia ; *Family Characteristics ; Female ; Humans ; *Literacy ; Male ; Middle Aged ; Rural Population ; *Toilet Facilities ; }, abstract = {OBJECTIVE: The study was conducted on 313 model and 313 non model households to assess latrine utilization and factors affecting among model and non-model families.

RESULT: About 225 (71.9%) model and 144 (46%) non-model participants declared that they utilize their latrine which gave the overall utilization rate of 369 (58.9%). Households with primary and above education were two times (AOR = 2.03, 95% CI 1.427, 4.638) more likely to utilize latrine as compared with illiterate households. Cleanness of the latrine was also found to be associated with latrine utilization in both model and non-model families. Age, type of latrine, latrine supper structure, cleanness and observable soap near the latrine in model families and age, educational status, occupation, latrine privacy and cleanness in non-model families were identified as a statistical significant factor for latrine utilization.}, } @article {pmid30103797, year = {2018}, author = {Molla, E and Mamo, H}, title = {Soil-transmitted helminth infections, anemia and undernutrition among schoolchildren in Yirgacheffee, South Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {585}, pmid = {30103797}, issn = {1756-0500}, mesh = {Adolescent ; Anemia/epidemiology/*etiology ; Animals ; Child ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Feces ; Female ; Helminthiasis/*complications/epidemiology ; Helminths ; Humans ; Male ; Malnutrition/epidemiology/*etiology ; Prevalence ; Soil ; Trichuris/isolation & purification ; }, abstract = {OBJECTIVE: Current data on soil-transmitted helminth infections, anemia and malnutrition that are largely neglected is vital to the control and management of them in a specific setting. This study was, therefore, aimed at determining the status of the three health concerns in one of the high-risk groups, schoolchildren, in South Ethiopia.

RESULTS: Among the 443 sampled schoolchildren, 54% were infected with soil-transmitted helminths (STHs) and 15.4% of them had anaemia, while the prevalence rate of undernutrition was 28.9%. Species-wise, prevalence of STH infections was 21.7, 16.7, 7.2 and 8.4% for Ascaris lumbricoides, the hookworms, Trichuris trichiura and mixed infections, respectively. Untreated drinking water, high frequency of sucking fingernails and open defecation were significantly associated with risk of getting STH infections. Child positivity for STH infection didn't show any significant association with undernutrition of the children. Anaemia was significantly correlated with hookworm (adjusted odds ratio (AOR) = 2.96, 95% confidence interval (CI) = 2.15, 4.86), A. lumbricoides (AOR = 1.93, 95% CI = 1.13, 3.01) and polyparasitism (AOR = 1.54, 95% CI = 1.04, 2.64). In addition, children with heavy intensities of hookworm infections and those undernourished were more likely to suffer from anaemia with P = 0.001 and P = 0.007, respectively.}, } @article {pmid30103796, year = {2018}, author = {Tasew, H and Gebrekristos, K and Kidanu, K and Mariye, T and Teklay, G}, title = {Determinants of hypothermia on neonates admitted to the intensive care unit of public hospitals of Central Zone, Tigray, Ethiopia 2017: unmatched case-control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {576}, pmid = {30103796}, issn = {1756-0500}, mesh = {Case-Control Studies ; Ethiopia ; Hospitals, Public/*statistics & numerical data ; Humans ; Hypothermia/*etiology ; Infant, Newborn ; Infant, Newborn, Diseases/*etiology ; Intensive Care Units ; }, abstract = {OBJECTIVE: This study aims to identify determinants of hypothermia in neonates in neonatal intensive care unit of public hospitals of Central Zone Tigray, Ethiopia in 2017.

RESULTS: A total of 88 cases and 176 controls were included in this study. Ninety-one percent cases and 86.4% controls were in the 1st week of neonate age. Multivariable logistic regression analysis showed that delayed initiation of breastfeeding [AOR = 7.23; 95% CI (2.75, 18.99)], low birth weight [AOR = 8.51; 95% CI (2.71, 26.73)], preterm [AOR = 3.689; 95% CI (1.359, 10.012)], low APGAR score at 5th min [AOR = 3.71; 95% CI (1.57, 8.79)], skin to skin contact [AOR = 6.23; 95% CI (2.523, 15.358)], night time delivery [AOR = 6.25; 95% CI (2.58, 15.12)] and bathed within 24 h [AOR = 10.06; 95% CI (3.86, 26.22)] were independent risk factors of neonatal hypothermia.}, } @article {pmid30103762, year = {2018}, author = {Libbrecht, R and Oxley, PR and Kronauer, DJC}, title = {Clonal raider ant brain transcriptomics identifies candidate molecular mechanisms for reproductive division of labor.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {89}, pmid = {30103762}, issn = {1741-7007}, support = {1DP2GM105454-01/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Division of labor between reproductive queens and workers that perform brood care is a hallmark of insect societies. However, studies of the molecular basis of this fundamental dichotomy are limited by the fact that the caste of an individual cannot typically be experimentally manipulated at the adult stage. Here we take advantage of the unique biology of the clonal raider ant, Ooceraea biroi, to study brain gene expression dynamics during experimentally induced transitions between reproductive and brood care behavior.

RESULTS: Introducing larvae that inhibit reproduction and induce brood care behavior causes much faster changes in adult gene expression than removing larvae. In addition, the general patterns of gene expression differ depending on whether ants transition from reproduction to brood care or vice versa, indicating that gene expression changes between phases are cyclic rather than pendular. Finally, we identify genes that could play upstream roles in regulating reproduction and behavior because they show large and early expression changes in one or both transitions.

CONCLUSIONS: Our analyses reveal that the nature and timing of gene expression changes differ substantially depending on the direction of the transition, and identify a suite of promising candidate molecular regulators of reproductive division of labor that can now be characterized further in both social and solitary animal models. This study contributes to understanding the molecular regulation of reproduction and behavior, as well as the organization and evolution of insect societies.}, } @article {pmid30103702, year = {2018}, author = {Iorio, F and Behan, FM and Gonçalves, E and Bhosle, SG and Chen, E and Shepherd, R and Beaver, C and Ansari, R and Pooley, R and Wilkinson, P and Harper, S and Butler, AP and Stronach, EA and Saez-Rodriguez, J and Yusa, K and Garnett, MJ}, title = {Unsupervised correction of gene-independent cell responses to CRISPR-Cas9 targeting.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {604}, pmid = {30103702}, issn = {1471-2164}, support = {015//Open Targets/ ; C44943/A22536//Cancer Research UK/United Kingdom ; SU2C-AACR-DT1213//Cancer Research UK/United Kingdom ; 102696//Wellcome Trust (GB)/ ; }, mesh = {*CRISPR-Cas Systems ; Cell Line, Tumor ; DNA Copy Number Variations ; Gene Amplification ; Gene Knockout Techniques/methods ; Gene Targeting/*methods ; Genes, Essential ; *Genome, Human ; High-Throughput Screening Assays ; Humans ; Neoplasms/*genetics ; Sequence Analysis, DNA ; Software ; }, abstract = {BACKGROUND: Genome editing by CRISPR-Cas9 technology allows large-scale screening of gene essentiality in cancer. A confounding factor when interpreting CRISPR-Cas9 screens is the high false-positive rate in detecting essential genes within copy number amplified regions of the genome. We have developed the computational tool CRISPRcleanR which is capable of identifying and correcting gene-independent responses to CRISPR-Cas9 targeting. CRISPRcleanR uses an unsupervised approach based on the segmentation of single-guide RNA fold change values across the genome, without making any assumption about the copy number status of the targeted genes.

RESULTS: Applying our method to existing and newly generated genome-wide essentiality profiles from 15 cancer cell lines, we demonstrate that CRISPRcleanR reduces false positives when calling essential genes, correcting biases within and outside of amplified regions, while maintaining true positive rates. Established cancer dependencies and essentiality signals of amplified cancer driver genes are detectable post-correction. CRISPRcleanR reports sgRNA fold changes and normalised read counts, is therefore compatible with downstream analysis tools, and works with multiple sgRNA libraries.

CONCLUSIONS: CRISPRcleanR is a versatile open-source tool for the analysis of CRISPR-Cas9 knockout screens to identify essential genes.}, } @article {pmid30103701, year = {2018}, author = {Shimada, T and Endo, T and Fujii, H and Nakano, M and Sugiyama, A and Daido, G and Ohta, S and Yoshioka, T and Omura, M}, title = {MITE insertion-dependent expression of CitRKD1 with a RWP-RK domain regulates somatic embryogenesis in citrus nucellar tissues.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {166}, pmid = {30103701}, issn = {1471-2229}, abstract = {BACKGROUND: Somatic embryogenesis in nucellar tissues is widely recognized to induce polyembryony in major citrus varieties such as sweet oranges, satsuma mandarins and lemons. This capability for apomixis is attractive in agricultural production systems using hybrid seeds, and many studies have been performed to elucidate the molecular mechanisms of various types of apomixis. To identify the gene responsible for somatic embryogenesis in citrus, a custom oligo-DNA microarray including predicted genes in the citrus polyembryonic locus was used to compare the expression profiles in reproductive tissues between monoembryonic and polyembryonic varieties. The full length of CitRKD1, which was identified as a candidate gene responsible for citrus somatic embryogenesis, was isolated from satsuma mandarin and its molecular function was investigated using transgenic 'Hamlin' sweet orange by antisense-overexpression.

RESULTS: The candidate gene CitRKD1, predominantly transcribed in reproductive tissues of polyembryonic varieties, is a member of the plant RWP-RK domain-containing protein. CitRKD1 of satsuma mandarin comprised two alleles (CitRKD1-mg1 and CitRKD1-mg2) at the polyembryonic locus controlling embryonic type (mono/polyembryony) that were structurally divided into two types with or without a miniature inverted-repeat transposable element (MITE)-like insertion in the upstream region. CitRKD1-mg2 with the MITE insertion was the predominant transcript in flowers and young fruits where somatic embryogenesis of nucellar cells occurred. Loss of CitRKD1 function by antisense-overexpression abolished somatic embryogenesis in transgenic sweet orange and the transgenic T1 plants were confirmed to derive from zygotic embryos produced by self-pollination by DNA diagnosis. Genotyping PCR analysis of 95 citrus traditional and breeding varieties revealed that the CitRKD1 allele with the MITE insertion (polyembryonic allele) was dominant and major citrus varieties with the polyembryonic allele produced polyembryonic seeds.

CONCLUSION: CitRKD1 at the polyembryonic locus plays a principal role in regulating citrus somatic embryogenesis. CitRKD1 comprised multiple alleles that were divided into two types, polyembryonic alleles with a MITE insertion in the upstream region and monoembryonic alleles without it. CitRKD1 was transcribed in reproductive tissues of polyembryonic varieties with the polyembryonic allele. The MITE insertion in the upstream region of CitRKD1 might be involved in regulating the transcription of CitRKD1.}, } @article {pmid30103700, year = {2018}, author = {Liu, Z and Zhao, Y and Wang, X and Yang, M and Guo, C and Xiao, K}, title = {TaNBP1, a guanine nucleotide-binding subunit gene of wheat, is essential in the regulation of N starvation adaptation via modulating N acquisition and ROS homeostasis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {167}, pmid = {30103700}, issn = {1471-2229}, support = {(no. 31571664)//National Natural Science Foundation of China (no. 31571664)/ ; }, abstract = {BACKGROUND: Nitrate (NO3-) is the major source of nitrogen (N) for higher plants aside from its function in transducing the N signaling. Improving N use efficiency of crops has been an effective strategy for promotion of the sustainable agriculture worldwide. The regulatory pathways associating with N uptake and the corresponding biochemical processes impact largely on plant N starvation tolerance. Thus, exploration of the molecular mechanism underlying nitrogen use efficiency (NUE) and the gene wealth will pave a way for molecular breeding of N starvation-tolerant crop cultivars.

RESULTS: In the current study, we characterized the function of TaNBP1, a guanine nucleotide-binding protein subunit beta gene of wheat (T. aestivum), in mediating the plant N starvation response. TaNBP1 protein harbors a conserved W40 domain and the TaNBP1-GFP (green fluorescence protein) signals concentrate at positions of cytoplasm membrane and cytosol. TaNBP1 transcripts are induced in roots and leaves upon N starvation stress and that this upregulated expression is recovered by N recovery treatment. TaNBP1 overexpression confers improved phenotype, enlarged root system architecture (RSA), and increased biomass for plants upon N deprivation relative to the wild type, associating with its role in enhancing N accumulation and improving reactive oxygen species (ROS) homeostasis. Nitrate transporter (NRT) gene NtNRT2.2 and antioxidant enzyme genes NtSOD1, NtSOD2, and NtCAT1 are transcriptionally regulated under TaNBP1 and contribute to the improved N acquisition and the increased AE activities of plants.

CONCLUSIONS: Altogether, TaNBP1 is transcriptional response to N starvation stress. Overexpression of this gene enhances plant N starvation adaptation via improvement of N uptake and cellular ROS homeostasis by modifying transcription of NRT gene NtNRT2.2 and antioxidant enzyme genes NtSOD1, NtSOD2, and NtCAT1, respectively. Our research helps to understand the mechanism underlying plant N starvation response and benefits to genetically engineer crop cultivars with improved NUE under the N-saving cultivation conditions.}, } @article {pmid30103699, year = {2018}, author = {Yang, B and Jiao, B and Ge, W and Zhang, X and Wang, S and Zhao, H and Wang, X}, title = {Transcriptome sequencing to detect the potential role of long non-coding RNAs in bovine mammary gland during the dry and lactation period.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {605}, pmid = {30103699}, issn = {1471-2164}, support = {NCET-13-0485//Program for New Excellent Talents in University of China/ ; CXGC2016B03//Agricultural Scientific and Technological Innovation Project of Shandong Academy of Agricultural Science/ ; }, mesh = {Animals ; Cattle ; Female ; Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/*methods ; *Lactation ; Mammary Glands, Animal/*metabolism/physiology ; RNA, Long Noncoding/*genetics ; Signal Transduction ; Whole Exome Sequencing/*methods ; }, abstract = {BACKGROUND: It is known that long non-coding RNAs (lncRNAs) play an important role in various biological processes, including cell proliferation, differentiation and apoptosis. However, their functions and profiles in lactation cycle of dairy cows are largely unknown. In this study, lncRNA-seq technique was employed to compare the expression profiles of lncRNAs and mRNAs from Chinese Holstein mammary gland in dry and lactation period.

RESULT: Totally 3746 differentially expressed lncRNAs (DELs) and 2890 differentially expressed genes (DEGs) were identified from the dry and lactation mammary glands of Holstein cows. Functional enrichment analysis on target genes of lncRNAs indicated that these genes were involved in lactation-related signaling pathways, including cell cycle, JAK-STAT, cell adhesion, and PI3K-Akt signaling pathways. Additionally, the interaction between lncRNAs and their potential miRNAs was predicted and partly verified. The result indicated that the lactation-associated miR-221 might interact with lncRNAs TCONS_00040268, TCONS_00137654, TCONS_00071659 and TCONS_00000352, which revealed that these lncRNAs might be important regulators for lactation cycle.

CONCLUSION: This study provides a resource for lncRNA research on lactation cycle of bovine mammary gland. Besides, the interaction between lncRNAs and the specific miRNA is revealed. It expands our knowledge about lncRNA and miRNA biology as well as contributes to clarify the regulation of lactation cycle of bovine mammary gland.}, } @article {pmid30103675, year = {2018}, author = {Chen, NWG and Serres-Giardi, L and Ruh, M and Briand, M and Bonneau, S and Darrasse, A and Barbe, V and Gagnevin, L and Koebnik, R and Jacques, MA}, title = {Horizontal gene transfer plays a major role in the pathological convergence of Xanthomonas lineages on common bean.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {606}, pmid = {30103675}, issn = {1471-2164}, support = {ANR-2010-GENM-013-02//Agence Nationale de la Recherche/ ; ANR-10-INBS-0009//Agence Nationale de la Recherche/ ; 154/AP2006-2007//Genoscope/ ; 18/AP2009-2010//Genoscope/ ; }, mesh = {Bacterial Proteins/genetics ; *Gene Transfer, Horizontal ; Genome, Bacterial ; *Host-Pathogen Interactions ; Phaseolus/genetics/growth & development/*microbiology ; Phylogeny ; Plant Diseases/*genetics/microbiology ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Virulence ; Whole Genome Sequencing ; Xanthomonas/classification/*pathogenicity ; }, abstract = {BACKGROUND: Host specialization is a hallmark of numerous plant pathogens including bacteria, fungi, oomycetes and viruses. Yet, the molecular and evolutionary bases of host specificity are poorly understood. In some cases, pathological convergence is observed for individuals belonging to distant phylogenetic clades. This is the case for Xanthomonas strains responsible for common bacterial blight of bean, spread across four genetic lineages. All the strains from these four lineages converged for pathogenicity on common bean, implying possible gene convergences and/or sharing of a common arsenal of genes conferring the ability to infect common bean.

RESULTS: To search for genes involved in common bean specificity, we used a combination of whole-genome analyses without a priori, including a genome scan based on k-mer search. Analysis of 72 genomes from a collection of Xanthomonas pathovars unveiled 115 genes bearing DNA sequences specific to strains responsible for common bacterial blight, including 20 genes located on a plasmid. Of these 115 genes, 88 were involved in successive events of horizontal gene transfers among the four genetic lineages, and 44 contained nonsynonymous polymorphisms unique to the causal agents of common bacterial blight.

CONCLUSIONS: Our study revealed that host specificity of common bacterial blight agents is associated with a combination of horizontal transfers of genes, and highlights the role of plasmids in these horizontal transfers.}, } @article {pmid30103674, year = {2018}, author = {Li, H and Yuan, J and Wu, M and Han, Z and Li, L and Jiang, H and Jia, Y and Han, X and Liu, M and Sun, D and Chen, C and Song, W and Wang, C}, title = {Transcriptome and DNA methylome reveal insights into yield heterosis in the curds of broccoli (Brassica oleracea L var. italic).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {168}, pmid = {30103674}, issn = {1471-2229}, support = {31470669//National Natural Science Foundation of China/ ; 31401889//National Natural Science Foundation of China (CN)/ ; No.14JCZDJC34000//Natural Science Foundation of Tianjin Municipal Science and Technology Commission/ ; 15JCQNJC15100//Natural Science Foundation of Tianjin/ ; 2017YPY004//Graduate education quality improvement projects of Tianjin Agricultural University/ ; }, abstract = {BACKGROUND: Curds are the main edible organs, which exhibit remarkable yield heterosis in F1 hybrid broccoli. However, the molecular basis underlying heterosis in broccoli remains elusive.

RESULTS: In the present study, transcriptome profiles revealed that the hybridization made most genes show additive expression patterns in hybrid broccoli. The differentially expressed genes including the non-additively expressed genes detected in the hybrid broccoli and its parents were mainly involved in light, hormone and hydrogen peroxide-mediated signaling pathways, responses to stresses, and regulation of floral development, which suggested that these biological processes should play crucial roles in the yield heterosis of broccoli. Among them, light and hydrogen peroxide-mediated signaling pathways represent two novel classes of regulatory processes that could function in yield or biomass heterosis of plants. Totally, 53 candidate genes closely involved in curd yield heterosis were identified. Methylome data indicated that the DNA methylation ratio of the hybrids was higher than that of their parents. However, the DNA methylation levels of most sites also displayed additive expression patterns. These sites with differential methylation levels were predominant in the intergenic regions. In most cases, the changes of DNA methylation levels in gene regions did not significantly affect their expression levels.

CONCLUSIONS: The differentially expressed genes, the regulatory processes and the possible roles of DNA methylation modification in the formation of curd yield heterotic trait were discovered. These findings provided comprehensive insights into the curd yield heterosis in broccoli, and were significant for breeding high-yield broccoli varieties.}, } @article {pmid30103673, year = {2018}, author = {Meng, X and Zhang, P and Chen, Q and Wang, J and Chen, M}, title = {Identification and characterization of ncRNA-associated ceRNA networks in Arabidopsis leaf development.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {607}, pmid = {30103673}, issn = {1471-2164}, support = {2016YFA0501704//National Key Research and Development Program of China/ ; 31771477, 31571366 and 31450110068//National Natural Science Foundation of China/ ; }, mesh = {Arabidopsis/*genetics/growth & development/physiology ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; Plant Leaves/*genetics/growth & development/physiology ; RNA/*genetics ; RNA, Untranslated/*genetics ; Transcriptome ; }, abstract = {BACKGROUND: Leaf development is a complex biological process that is accompanied by wide transcriptional changes. Many protein-coding genes have been characterized in plant leaves, but little attention has been given to noncoding RNAs (ncRNAs). Moreover, increasing evidence indicates that an intricate interplay among RNA species, including protein-coding RNAs and ncRNAs, exists in eukaryotic transcriptomes, however, it remains elusive in plant leaves.

RESULTS: We detected novel ncRNAs, such as circular RNAs (circRNAs) and long noncoding RNAs (lncRNAs), and further constructed and analyzed their associated competitive endogenous RNA (ceRNA) networks in Arabidopsis leaves. Transcriptome profiling showed extensive changes during leaf development. In addition, comprehensive detection of circRNAs in other plant leaves suggested that circRNAs are widespread in plant leaves. To investigate the complex post-transcriptional interactions in Arabidopsis leaves, we constructed a global circRNA/lncRNA-associated ceRNA network. Functional analysis revealed that ceRNAs were highly correlated with leaf development. These ceRNAs could be divided into six clusters, which were enriched for different functional classes. Stage-specific ceRNA networks were further constructed and comparative analysis revealed different roles of stage common and specific hub ceRNAs.

CONCLUSIONS: Our results demonstrate that understanding the ceRNA interactions will lead insights into gene regulations implicated in leaf development.}, } @article {pmid30102976, year = {2018}, author = {Baron, S and van der Merwe, NA and Maritz-Olivier, C}, title = {The genetic relationship between R. microplus and R. decoloratus ticks in South Africa and their population structure.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {60-69}, doi = {10.1016/j.ympev.2018.08.003}, pmid = {30102976}, issn = {1095-9513}, abstract = {Rhipicephalus microplus and R. decoloratus are one-host ticks that preferentially feed on cattle. They are capable of transmitting various tick-borne pathogens which may be detrimental to the agricultural and livestock industry in South Africa. Previous studies have shown that R. microplus forms five lineages in the R. microplus complex, segregating into different geographical areas based on mitochondrial markers. This study examined the phylogenetic relationship within and between R. microplus and R. decoloratus using the nuclear internal transcribed spacer 2 (ITS2) and mitochondrial cytochrome oxidase subunit I (COI) genes. The results showed that the nuclear ITS2 marker is informative for interspecific variation but lacks the resolution for intraspecific variation. Analysis of the mitochondrial COI gene revealed that R. microplus ticks from South Africa grouped into a clade comprised of ticks from Asia and South America. The population structure of these two tick species was also investigated using novel microsatellite markers. Population structure analyses revealed that both the R. microplus and R. decoloratus populations presented with two genetic clusters. Rhipicephalus microplus ticks from the Kwa-Zulu Natal (KZN) province belonged to cluster 1, and those from the Eastern Cape (EC) province predominantly grouped into cluster 2. No observable population structure was noted for R. decoloratus. The overlap of genetic clusters in both species could be attributed to inbreeding between the regions by unrestricted movement of cattle across provinces. Such movement promotes tick mobility, gene flow and the homogenisation of tick populations.}, } @article {pmid30102810, year = {2018}, author = {Murali, G and Merilaita, S and Kodandaramaiah, U}, title = {Grab my tail: evolution of dazzle stripes and colourful tails in lizards.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1675-1688}, doi = {10.1111/jeb.13364}, pmid = {30102810}, issn = {1420-9101}, support = {DST/INSPIRE/04/2013/000476//Department of Science and Technology/ ; //IISER-TVM/ ; //Åbo Akademi University/ ; }, abstract = {Understanding the functions of animal coloration has been a long-standing question in evolutionary biology. For example, the widespread occurrence of striking longitudinal stripes and colourful tails in lizards begs for an explanation. Experiments have suggested that colourful tails can deflect attacks towards the tail (the 'deflection' hypothesis), which is sacrificable in most lizards, thereby increasing the chance of escape. Studies also suggest that in moving lizards, longitudinal body stripes can redirect predators' strikes towards the tail through the 'motion dazzle' effect. Despite these experimental studies, the ecological factors associated with the evolution of such striking colorations remain unexplored. Here, we investigated whether predictions from motion dazzle and attack deflection could explain the widespread occurrence of these striking marks using comparative methods and information on eco-physiological variables (caudal autotomy, diel activity, microhabitat and body temperature) potentially linked to their functioning. We found both longitudinal stripes and colourful tails are associated with diurnal activity and with the ability to lose the tail. Compared to stripeless species, striped species are more likely to be ground-dwelling and have higher body temperature, emphasizing the connection of stripes to mobility and rapid escape strategy. Colourful tails and stripes have evolved multiple times in a correlated fashion, suggesting that their functions may be linked. Overall, our results together with previous experimental studies support the notion that stripes and colourful tails in lizards may have protective functions based on deflective and motion dazzle effects.}, } @article {pmid30102395, year = {2018}, author = {Manzano-Marín, A and Coeur d'acier, A and Clamens, AL and Orvain, C and Cruaud, C and Barbe, V and Jousselin, E}, title = {A Freeloader? The Highly Eroded Yet Large Genome of the Serratia symbiotica Symbiont of Cinara strobi.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2178-2189}, pmid = {30102395}, issn = {1759-6653}, abstract = {Genome reduction is pervasive among maternally inherited bacterial endosymbionts. This genome reduction can eventually lead to serious deterioration of essential metabolic pathways, thus rendering an obligate endosymbiont unable to provide essential nutrients to its host. This loss of essential pathways can lead to either symbiont complementation (sharing of the nutrient production with a novel co-obligate symbiont) or symbiont replacement (complete takeover of nutrient production by the novel symbiont). However, the process by which these two evolutionary events happen remains somewhat enigmatic by the lack of examples of intermediate stages of this process. Cinara aphids (Hemiptera: Aphididae) typically harbor two obligate bacterial symbionts: Buchnera and Serratia symbiotica. However, the latter has been replaced by different bacterial taxa in specific lineages, and thus species within this aphid lineage could provide important clues into the process of symbiont replacement. In the present study, using 16S rRNA high-throughput amplicon sequencing, we determined that the aphid Cinara strobi harbors not two, but three fixed bacterial symbionts: Buchnera aphidicola, a Sodalis sp., and S. symbiotica. Through genome assembly and genome-based metabolic inference, we have found that only the first two symbionts (Buchnera and Sodalis) actually contribute to the hosts' supply of essential nutrients while S. symbiotica has become unable to contribute towards this task. We found that S. symbiotica has a rather large and highly eroded genome which codes only for a few proteins and displays extensive pseudogenization. Thus, we propose an ongoing symbiont replacement within C. strobi, in which a once "competent" S. symbiotica does no longer contribute towards the beneficial association. These results suggest that in dual symbiotic systems, when a substitute cosymbiont is available, genome deterioration can precede genome reduction and a symbiont can be maintained despite the apparent lack of benefit to its host.}, } @article {pmid30102365, year = {2018}, author = {Brennan, RS and Healy, TM and Bryant, HJ and La, MV and Schulte, PM and Whitehead, A}, title = {Integrative Population and Physiological Genomics Reveals Mechanisms of Adaptation in Killifish.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2639-2653}, doi = {10.1093/molbev/msy154}, pmid = {30102365}, issn = {1537-1719}, abstract = {Adaptive divergence between marine and freshwater (FW) environments is important in generating phyletic diversity within fishes, but the genetic basis of this process remains poorly understood. Genome selection scans can identify adaptive loci, but incomplete knowledge of genotype-phenotype connections makes interpreting their significance difficult. In contrast, association mapping (genome-wide association mapping [GWAS], random forest [RF] analyses) links genotype to phenotype, but offer limited insight into the evolutionary forces shaping variation. Here, we combined GWAS, RF, and selection scans to identify loci important in adaptation to FW environments. We utilized FW-native and brackish water (BW)-native populations of Atlantic killifish (Fundulus heteroclitus) as well as a naturally admixed population between the two. We measured morphology and multiple physiological traits that differ between populations and may contribute to osmotic adaptation (salinity tolerance, hypoxia tolerance, metabolic rate, body shape) and used a reduced representation approach for genome-wide genotyping. Our results show patterns of population divergence in physiological capabilities that are consistent with local adaptation. Population genomic scans between BW-native and FW-native populations identified genomic regions evolving by natural selection, whereas association mapping revealed loci that contribute to variation for each trait. There was substantial overlap in the genomic regions putatively under selection and loci associated with phenotypic traits, particularly for salinity tolerance, suggesting that these regions and genes are important for adaptive divergence between BW and FW environments. Together, these data provide insight into the mechanisms that enable diversification of fishes across osmotic boundaries.}, } @article {pmid30102363, year = {2018}, author = {Thawornwattana, Y and Dalquen, D and Yang, Z}, title = {Coalescent Analysis of Phylogenomic Data Confidently Resolves the Species Relationships in the Anopheles gambiae Species Complex.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2512-2527}, pmid = {30102363}, issn = {1537-1719}, abstract = {Deep coalescence and introgression make it challenging to infer phylogenetic relationships among closely related species that arose through radiative speciation events. Despite numerous phylogenetic analyses and the availability of whole genomes, the phylogeny in the Anopheles gambiae species complex has not been confidently resolved. Here we extract over 80, 000 coding and noncoding short segments (called loci) from the genomes of six members of the species complex and use a Bayesian method under the multispecies coalescent model to infer the species tree, which takes into account genealogical heterogeneity across the genome and uncertainty in the gene trees. We obtained a robust estimate of the species tree from the distal region of the X chromosome: (A. merus, ((A. melas, (A. arabiensis, A. quadriannulatus)), (A. gambiae, A. coluzzii))), with A. merus to be the earliest branching species. This species tree agrees with the chromosome inversion phylogeny and provides a parsimonious interpretation of inversion and introgression events. Simulation informed by the real data suggest that the coalescent approach is reliable while the sliding-window analysis used in a previous phylogenomic study generates artifactual species trees. Likelihood ratio test of gene flow revealed strong evidence of autosomal introgression from A. arabiensis into A. gambiae (at the average rate of ∼0.2 migrants per generation), but not in the opposite direction, and introgression of the 3 L chromosomal region from A. merus into A. quadriannulatus. Our results highlight the importance of accommodating incomplete lineage sorting and introgression in phylogenomic analyses of species that arose through recent radiative speciation events.}, } @article {pmid30102357, year = {2018}, author = {Brauchle, M and Bilican, A and Eyer, C and Bailly, X and Martínez, P and Ladurner, P and Bruggmann, R and Sprecher, SG}, title = {Xenacoelomorpha Survey Reveals That All 11 Animal Homeobox Gene Classes Were Present in the First Bilaterians.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2205-2217}, pmid = {30102357}, issn = {1759-6653}, abstract = {Homeodomain transcription factors are involved in many developmental processes across animals and have been linked to body plan evolution. Detailed classifications of these proteins identified 11 distinct classes of homeodomain proteins in animal genomes, each harboring specific sequence composition and protein domains. Although humans contain the full set of classes, Drosophila melanogaster and Caenorhabditis elegans each lack one specific class. Furthermore, representative previous analyses in sponges, ctenophores, and cnidarians could not identify several classes in those nonbilaterian metazoan taxa. Consequently, it is currently unknown when certain homeodomain protein classes first evolved during animal evolution. Here, we investigate representatives of the sister group to all remaining bilaterians, the Xenacoelomorpha. We analyzed three acoel, one nemertodermatid, and one Xenoturbella transcriptomes and identified their expressed homeodomain protein content. We report the identification of representatives of all 11 classes of animal homeodomain transcription factors in Xenacoelomorpha and we describe and classify their homeobox genes relative to the established animal homeodomain protein families. Our findings suggest that the genome of the last common ancestor of bilateria contained the full set of these gene classes, supporting the subsequent diversification of bilaterians.}, } @article {pmid30102350, year = {2018}, author = {Lo, WS and Gasparich, GE and Kuo, CH}, title = {Convergent Evolution among Ruminant-Pathogenic Mycoplasma Involved Extensive Gene Content Changes.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2130-2139}, pmid = {30102350}, issn = {1759-6653}, mesh = {Biological Evolution ; Genes, Bacterial ; Gram-Negative Bacteria/classification/genetics ; Mycoplasma/*classification/*genetics ; Phylogeny ; Synteny ; }, abstract = {Convergent evolution, a process by which organisms evolved independently to have similar traits, provides opportunities to understand adaptation. The bacterial genus Mycoplasma contains multiple species that evolved independently to become ruminant pathogens, which represents an interesting study system for investigating the process. In this work, we determined the genome sequences of 11 Entomoplasma/Mesoplasma species. This new data set, together with the other available Mollicutes genomes, provided comprehensive taxon sampling for inferring the gene content evolution that led to the emergence of Mycoplasma Mycoides cluster. Our results indicated that the most recent common ancestor (MRCA) of the Mycoides-Entomoplasmataceae clade lost ∼15% of the core genes when it diverged from the Spiroplasma Apis clade. After this initial wave of genome reduction, relatively few gene gains or losses were inferred until the emergence of the Mycoides cluster. Compared with those Entomoplasmataceae lineages that maintained the association with insects, the MRCA of the Mycoides cluster experienced a second wave of gene losses, as well as acquiring >100 novel genes through horizontal gene transfer. These gene acquisitions involved many with the Mycoplasma Hominis/Pneumoniae lineages as the putative donors, suggesting that gene exchanges among these vertebrate symbionts with distinct phylogenetic affiliations may be important in the emergence of the Mycoides cluster. These findings demonstrated that the gene content of bacterial genomes could be exceedingly dynamic, even for those symbionts with highly reduced genomes. Moreover, the emergence of novel pathogens may involve extensive remodeling of gene content, rather than acquisition of few virulence genes.}, } @article {pmid30102348, year = {2018}, author = {Li, ZW and Hou, XH and Chen, JF and Xu, YC and Wu, Q and González, J and Guo, YL}, title = {Transposable Elements Contribute to the Adaptation of Arabidopsis thaliana.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2140-2150}, pmid = {30102348}, issn = {1759-6653}, mesh = {Adaptation, Physiological ; Arabidopsis/classification/*genetics/physiology ; *DNA Transposable Elements ; Evolution, Molecular ; }, abstract = {Transposable elements (TEs) are mobile genetic elements with very high mutation rates that play important roles in shaping genome architecture and regulating phenotypic variation. However, the extent to which TEs influence the adaptation of organisms in their natural habitats is largely unknown. Here, we scanned 201 representative resequenced genomes from the model plant Arabidopsis thaliana and identified 2,311 polymorphic TEs from noncentromeric regions. We found expansion and contraction of different types of TEs in different A. thaliana populations. More importantly, we identified two TE insertions that are likely candidates to play a role in adaptive evolution. Our results highlight the importance of variations in TEs for the adaptation of plants in general in the context of rapid global climate change.}, } @article {pmid30102347, year = {2018}, author = {Gaouda, H and Hamaji, T and Yamamoto, K and Kawai-Toyooka, H and Suzuki, M and Noguchi, H and Minakuchi, Y and Toyoda, A and Fujiyama, A and Nozaki, H and Smith, DR}, title = {Exploring the Limits and Causes of Plastid Genome Expansion in Volvocine Green Algae.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2248-2254}, pmid = {30102347}, issn = {1759-6653}, abstract = {Plastid genomes are not normally celebrated for being large. But researchers are steadily uncovering algal lineages with big and, in rare cases, enormous plastid DNAs (ptDNAs), such as volvocine green algae. Plastome sequencing of five different volvocine species has revealed some of the largest, most repeat-dense plastomes on record, including that of Volvox carteri (∼525 kb). Volvocine algae have also been used as models for testing leading hypotheses on organelle genome evolution (e.g., the mutational hazard hypothesis), and it has been suggested that ptDNA inflation within this group might be a consequence of low mutation rates and/or the transition from a unicellular to multicellular existence. Here, we further our understanding of plastome size variation in the volvocine line by examining the ptDNA sequences of the colonial species Yamagishiella unicocca and Eudorina sp. NIES-3984 and the multicellular Volvox africanus, which are phylogenetically situated between species with known ptDNA sizes. Although V. africanus is closely related and similar in multicellular organization to V. carteri, its ptDNA was much less inflated than that of V. carteri. Synonymous- and noncoding-site nucleotide substitution rate analyses of these two Volvox ptDNAs suggest that there are drastically different plastid mutation rates operating in the coding versus intergenic regions, supporting the idea that error-prone DNA repair in repeat-rich intergenic spacers is contributing to genome expansion. Our results reinforce the idea that the volvocine line harbors extremes in plastome size but ultimately shed doubt on some of the previously proposed hypotheses for ptDNA inflation within the lineage.}, } @article {pmid30102345, year = {2018}, author = {Jabiol, J and Cornut, J and Tlili, A and Gessner, MO}, title = {Interactive effects of dissolved nitrogen, phosphorus and litter chemistry on stream fungal decomposers.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy151}, pmid = {30102345}, issn = {1574-6941}, abstract = {The enrichment of ecosystems by nutrients such as nitrogen (N) and phosphorus (P) has important ecological consequences. These include effects on plant litter decomposition in forest soils and forested headwater streams, where fungi play a pivotal role. However, our understanding of nutrient relationships on fungal communities associated with decomposing litter remains surprisingly incomplete. We conducted a fully factorial microcosm experiment with known communities of fungal decomposers from streams to assess the importance of dissolved N and P supply, as well as the atomic nutrient ratio (N:P), on fungal community succession, diversity, biomass and reproduction on three leaf-litter species differing in nutrient and lignin concentrations. Fungal biomass accrual and spore production were strongly controlled by external N supply, whereas P supply was much less important. The magnitude of these effects was mediated by litter quality, with stronger effects of dissolved N and P on lignin-poor and high N:P litter. N supply also influenced fungal diversity and species composition, acting as a pacemaker of community succession. Collectively, our data indicate that N was in much greater demand than predicted by standard stoichiometric models. The most parsimonious explanation for this deviation relates to the need of litter fungi to invest large amounts of N into degradative exoenzymes.}, } @article {pmid30102341, year = {2018}, author = {Westervelt, N and Chadwick, BP}, title = {Characterization of the ICCE Repeat in Mammals Reveals an Evolutionary Relationship with the DXZ4 Macrosatellite through Conserved CTCF Binding Motifs.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2190-2204}, pmid = {30102341}, issn = {1759-6653}, support = {R01 GM117003/GM/NIGMS NIH HHS/United States ; }, abstract = {Appreciation is growing for how chromosomes are organized in three-dimensional space at interphase. Microscopic and high throughput sequence-based studies have established that the mammalian inactive X chromosome (Xi) adopts an alternate conformation relative to the active X chromosome. The Xi is organized into several multi-megabase chromatin loops called superloops. At the base of these loops are superloop anchors, and in humans three of these anchors are composed of large tandem repeat DNA that include DXZ4, Functional Intergenic Repeating RNA Element, and Inactive-X CTCF-binding Contact Element (ICCE). Each repeat contains a high density of binding sites for the architectural organization protein CCCTC-binding factor (CTCF) which exclusively associates with the Xi allele in normal cells. Removal of DXZ4 from the Xi compromises proper folding of the chromosome. In this study, we report the characterization of the ICCE tandem repeat, for which very little is known. ICCE is embedded within an intron of the Nobody (NBDY) gene locus at Xp11.21. We find that primary DNA sequence conservation of ICCE is only retained in higher primates, but that ICCE orthologs exist beyond the primate lineage. Like DXZ4, what is conserved is organization of the underlying DNA into a large tandem repeat, physical location within the NBDY locus and conservation of short DNA sequences corresponding to specific CTCF and Yin Yang 1 binding motifs that correlate with female-specific DNA hypomethylation. Unlike DXZ4, ICCE is not common to all eutherian mammals. Analysis of certain ICCE CTCF motifs reveal striking similarity with the DXZ4 motif and support an evolutionary relationship between DXZ4 and ICCE.}, } @article {pmid30102146, year = {2018}, author = {Heo, J and Cho, H and Hong, SB and Kim, JS and Kwon, SW and Kim, SJ}, title = {Ottowia oryzae sp. nov., isolated from Andong sikhye, a Korean traditional rice beverage.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3096-3100}, doi = {10.1099/ijsem.0.002935}, pmid = {30102146}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Beverages/*microbiology ; Comamonadaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Food Microbiology ; Oryza ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, non-spore-forming, non-motile, short-rod-shaped bacterial strain, designated KADR8-3T, isolated from Andong sikhye in Andong-si, Gyeongsangbuk-do, Republic of Korea, was characterized using a polyphasic approach. On the basis of morphological, genetic and chemotaxonomic characteristics, it was determined to belong to the genus Ottowia. The phylogenetic similarity based on the 16S rRNA gene sequences indicated the strain formed a clade with Ottowia beijingensis GCS-AN-3T, Ottowia thiooxydans DSM 14619T, Ottowia pentelensis RB3-7T and 'Ottowia shaoguanensis' J5-66T, showing the highest similarity to O. beijingensis GCS-AN-3T (96.3 %). The major fatty acids were C16 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c). The predominant respiratory quinone was Q-8. The polar lipids present were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, two unidentified aminolipids and two unidentified lipids. The genomic DNA G+C content was 66.80 mol%. These results supported that strain KADR8-3T was clearly distinguishable from its closely related species and represents a novel species of the genus Ottowia, for which the name Ottowia oryzae is proposed. The type strain is KADR8-3T (=KACC 19325T=NBRC 113109T).}, } @article {pmid30102143, year = {2018}, author = {Roh, SG and Kim, MK and Park, S and Yun, BR and Park, J and Kim, MJ and Kim, YS and Kim, SB}, title = {Streptacidiphilus pinicola sp. nov., isolated from pine grove soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3149-3155}, doi = {10.1099/ijsem.0.002957}, pmid = {30102143}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Nucleic Acid Hybridization ; *Phylogeny ; Pinus/*microbiology ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomycetaceae/*classification/genetics/isolation & purification ; }, abstract = {A moderately acidophilic actinobacterial strain, designated MMS16-CNU450T, was isolated from pine grove soil, and its taxonomic position was analysed using a polyphasic approach. The isolate showed best growth at 30 °C, pH 6 and 0.5 % (w/v) NaCl. On the basis of 16S rRNA gene sequence similarity, the isolate was assigned to the genus Streptacidiphilus, and the closest species were Streptacidiphilus rugosus AM-16T (sequence similarity, 98.61 %), Streptacidiphilus melanogenes NBRC 103184T (98.53 %), Streptacidiphilus jiangxiensis NBRC 100920T (98.19 %) and Streptacidiphilus anmyonensis NBRC 103185T (98.05 %). The isolate formed a distinct cluster of its own within the Streptacidiphilusclade in the phylogenetic tree. Based on whole-genome comparison between the strain MMS16-CNU450T and the type strains of related species, the orthologous average nucleotide identity and in silico DNA-DNA hybridization values were in the range of 77.9-87.0 and 22.3-32.7 %, respectively. The DNA G+C content of the isolate was 68.6 mol%. The phylogenetic, phenotypic, chemotaxonomic and genomic data supported the affiliation of the strain to Streptacidiphilus, and the name Streptacidiphilus pinicola sp. nov. (type strain, MMS16-CNU450T=KCTC 49008T=JCM 32300T) is proposed accordingly.}, } @article {pmid30101976, year = {2018}, author = {Anstett, DN and Ahern, JR and Johnson, MTJ and Salminen, JP}, title = {Testing for latitudinal gradients in defense at the macroevolutionary scale.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2129-2143}, doi = {10.1111/evo.13579}, pmid = {30101976}, issn = {1558-5646}, support = {Discovery Grant - Marc Johnson//Natural Sciences and Engineering Research Council of Canada/ ; Vanier - Daniel//Natural Sciences and Engineering Research Council of Canada/ ; Anstett//Natural Sciences and Engineering Research Council of Canada/ ; Marc Johnson//Canadian Foundation for Innovation/ ; Ontario's Early Researcher Award - Marc Johnson//Government of Ontario,/ ; 258992 J.-P.//Suomen Akatemia/ ; Salminen//Suomen Akatemia/ ; }, abstract = {Plant defenses against herbivores are predicted to evolve to be greater in warmer climates, such as lower latitudes where herbivore pressure is also thought to be higher. Instead, recent findings are often inconsistent with this expectation, suggesting alternative hypotheses are needed. We tested for latitudinal gradients in plant defense evolution at the macroevolutionary scale by characterizing plant chemical defenses across 80 species of the evening primroses, spanning both North and South America. We quantified phenolics in leaves, flowers, and fruits, using advanced analytical chemistry techniques. Dominant individual ellagitannin compounds, total concentrations of ellagitannins, flavonoids, total phenolics, and compound diversity were quantified. Variation in these compounds was predicted with latitude, temperature, precipitation, and continent using phylogenetic generalized least squares (PGLS) multiple regression models. Latitude did not strongly explain variation in chemical defenses. Instead, fruit total ellagitannins, oenothein A, and total phenolics were greater in species inhabiting regions with colder climates. Using analytical chemistry and 80 species in two continents, we show that contrary to classic predictions, concentrations of secondary metabolites are not greater at lower latitudes or in warmer regions. We propose higher herbivore pressure in colder climates and gradients in resource availability as potential drivers of the observed patterns in Oenothera.}, } @article {pmid30101975, year = {2018}, author = {Walsh, J and Kovach, AI and Olsen, BJ and Shriver, WG and Lovette, IJ}, title = {Bidirectional adaptive introgression between two ecologically divergent sparrow species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2076-2089}, doi = {10.1111/evo.13581}, pmid = {30101975}, issn = {1558-5646}, support = {DBI 1523719//National Science Foundation Postdoctoral Research Fellowship in Biology/ ; }, abstract = {Natural hybrid zones can be used to dissect the mechanisms driving key evolutionary processes by allowing us to identify genomic regions important for establishing reproductive isolation and that allow for transfer of adaptive variation. We leverage whole-genome data in a system where two bird species, the saltmarsh (Ammospiza caudacuta) and Nelson's (A. nelsoni) sparrow, hybridize despite their relatively high background genetic differentiation and past ecological divergence. Adaptive introgression is plausible in this system because Nelson's sparrows are recent colonists of saltwater marshes, compared to the specialized saltmarsh sparrow that has a longer history of saltmarsh adaptation. Comparisons among whole-genome sequences of 34 individuals from allopatric and sympatric populations show that ongoing gene flow is shaping the genomic landscape, with allopatric populations exhibiting genome-wide FST estimates close to double of that observed in sympatry. We characterized patterns of introgression across the genome and identify regions that exhibit biased introgression into hybrids from one parental species. These regions offer compelling candidates for genes related to tidal marsh adaptations suggesting that adaptive introgression may be an important consequence of hybridization. These findings highlight the value of considering the landscapes of both genome-wide introgression and divergence when characterizing the evolutionary forces that drive speciation.}, } @article {pmid30101971, year = {2018}, author = {Meyer, ALS and Román-Palacios, C and Wiens, JJ}, title = {BAMM gives misleading rate estimates in simulated and empirical datasets.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2257-2266}, doi = {10.1111/evo.13574}, pmid = {30101971}, issn = {1558-5646}, support = {DEB 1655690//U.S. National Science Foundation/ ; }, abstract = {In a previous paper, we used simulations and empirical data to show that BAMM (Bayesian Analysis of Macroevolutionary Mixtures) can give misleading estimates of rates and rate shifts. In simulations, BAMM underestimated rate shifts across every tree analyzed, and assigned incorrect rates to most clades in most trees. In empirical analyses, BAMM behaved as expected from simulations, and assigned different rates to clades when clades were analyzed alone versus across the tree (i.e., with rate heterogeneity). Rabosky recently criticized our paper, focusing primarily on the idea that our comparison of BAMM to another approach (method-of-moments estimators of Magallón and Sanderson, or MS estimators) was unfair to BAMM. Here, we provide further evidence that BAMM gives misleading rate estimates in empirical studies. We then describe how Rabosky's rown method comparisons were either acknowledged as being problematic or were described inaccurately (to favor BAMM). Finally, we show that the MS estimators can perform well when rates vary over time, despite untested assertions that they require constant rates to be accurate. Many other methods are available for analyzing diversification rates: we argue that BAMM should be avoided for estimating both diversification rates and rate shifts.}, } @article {pmid30101493, year = {2018}, author = {Hood, GR and Zhang, L and Egan, SP}, title = {Digest: Disentangled bank: Less diverse urban environments modify the shape and magnitude of natural selection.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1972-1973}, doi = {10.1111/evo.13577}, pmid = {30101493}, issn = {1558-5646}, abstract = {Urbanization provides a natural experiment for biologists to test how anthropogenic environmental change affects evolution in real time and frames predictions for anticipated evolutionary outcomes worldwide. Start et al. () found that changes in species interactions (herbivore abundance and avian predation) along urbanization gradients predictably alter the shape and magnitude of natural selection on gall size (a defensive trait), suggesting that rapid global environmental change can alter species interactions, which may have foreseeable evolutionary consequences.}, } @article {pmid30101456, year = {2018}, author = {Clo, J}, title = {Digest: How mutational bias could explain the maintenance of sex.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1970-1971}, doi = {10.1111/evo.13578}, pmid = {30101456}, issn = {1558-5646}, abstract = {How does mutational bias affect the fitness of populations under different reproductive strategies? Vanhoenacker et al. (2018) found that mutational bias can greatly reduce the mean fitness of asexual populations, offering a new hypothesis for the maintenance of sex.}, } @article {pmid30101435, year = {2018}, author = {Rabosky, DL}, title = {BAMM at the court of false equivalency: A response to Meyer and Wiens.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2246-2256}, doi = {10.1111/evo.13566}, pmid = {30101435}, issn = {1558-5646}, abstract = {The software program BAMM has been widely used to study rates of speciation, extinction, and phenotypic evolution on phylogenetic trees. The program implements a model-based clustering algorithm to identify clades that share common macroevolutionary rate dynamics and to estimate parameters. A recent simulation study by Meyer and Wiens (M&W) argued that (1) a simple inference framework (MS) performs much better than BAMM, and (2) evolutionary rates inferred with BAMM are poorly correlated with true rates. I address two statistical concerns with their assessment that affect the generality of their conclusions. These considerations are not specific to BAMM and apply to other methods for estimating parameters from empirical data where the true grouping structure of the data is unknown. M&W constrain roughly half of the parameters in their MS analyses to their true values, but BAMM is given no such information and must estimate all parameters from the data. This information disparity results in a substantial degrees of freedom advantage for the MS estimators. When both methods are given equivalent information, BAMM outperforms the MS estimators.}, } @article {pmid30101430, year = {2018}, author = {Wolak, ME and Arcese, P and Keller, LF and Nietlisbach, P and Reid, JM}, title = {Sex-specific additive genetic variances and correlations for fitness in a song sparrow (Melospiza melodia) population subject to natural immigration and inbreeding.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2057-2075}, doi = {10.1111/evo.13575}, pmid = {30101430}, issn = {1558-5646}, support = {//European Research Council/ ; }, abstract = {Quantifying sex-specific additive genetic variance (VA) in fitness, and the cross-sex genetic correlation (rA), is prerequisite to predicting evolutionary dynamics and the magnitude of sexual conflict. Further, quantifying VA and rA in underlying fitness components, and genetic consequences of immigration and resulting gene flow, is required to identify mechanisms that maintain VA in fitness. However, these key parameters have rarely been estimated in wild populations experiencing natural environmental variation and immigration. We used comprehensive pedigree and life-history data from song sparrows (Melospiza melodia) to estimate VA and rA in sex-specific fitness and underlying fitness components, and to estimate additive genetic effects of immigrants alongside inbreeding depression. We found evidence of substantial VA in female and male fitness, with a moderate positive cross-sex rA . There was also substantial VA in male but not female adult reproductive success, and moderate VA in juvenile survival but not adult annual survival. Immigrants introduced alleles with negative additive genetic effects on local fitness, potentially reducing population mean fitness through migration load, but alleviating expression of inbreeding depression. Our results show that VA for fitness can be maintained in the wild, and be broadly concordant between the sexes despite marked sex-specific VA in reproductive success.}, } @article {pmid30101334, year = {2018}, author = {Kadnikov, VV and Mardanov, AV and Beletsky, AV and Banks, D and Pimenov, NV and Frank, YA and Karnachuk, OV and Ravin, NV}, title = {A metagenomic window into the 2-km-deep terrestrial subsurface aquifer revealed multiple pathways of organic matter decomposition.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy152}, pmid = {30101334}, issn = {1574-6941}, abstract = {We have sequenced metagenome of the microbial community of a deep subsurface thermal aquifer in the Tomsk Region of the Western Siberia, Russia. Our goal was the recovery of near-complete genomes of the community members to enable accurate reconstruction of metabolism and ecological roles of the microbial majority, including previously unstudied lineages. The water, obtained via a 2.6 km deep borehole 1-R, was anoxic, with a slightly alkaline pH, and a temperature around 45°C. Microbial community, as revealed by 16S rRNA gene profiling over 2 years, mostly consisted of sulfate-reducing Firmicutes and Deltaproteobacteria, and uncultured lineages of the phyla Chlorofexi, Ignavibacteriae and Aminicenantes (OP8). 25 composite genomes with more than 90% completeness were recovered from metagenome and used for metabolic reconstruction. Members of uncultured lineages of Chlorofexi and Ignavibacteriae are likely involved in degradation of carbohydrates by fermentation, and are also capable of aerobic and anaerobic respiration. The Chlorofexi bacterium has the Wood-Ljungdahl pathway of CO2 fixation. The recently identified candidate phylum Riflebacteria accounted for 5%-10% of microbial community. Metabolic reconstruction of a member of Riflebacteria predicted that it is an anaerobe capable to grow on carbohydrates by fermentation or dissimilatory Fe(III) reduction.}, } @article {pmid30101289, year = {2018}, author = {Shelton, JL and Andrews, RS and Akob, DM and DeVera, CA and Mumford, A and McCray, JE and McIntosh, JC}, title = {Microbial community composition of a hydrocarbon reservoir 40 years after a CO2 enhanced oil recovery flood.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, pmid = {30101289}, issn = {1574-6941}, abstract = {Injecting CO2 into depleted oil reservoirs to extract additional crude oil is a common enhanced oil recovery (CO2-EOR) technique. However, little is known about how in situ microbial communities may be impacted by CO2 flooding, or if any permanent microbiological changes occur after flooding has ceased. Formation water was collected from an oil field that was flooded for CO2-EOR in the 1980s, including samples from areas affected by or outside of the flood region, to determine the impacts of CO2-EOR on reservoir microbial communities. Archaea, specifically methanogens, were more abundant than bacteria in all samples, while identified bacteria exhibited much greater diversity than the archaea. Microbial communities in CO2-impacted and non-impacted samples did not significantly differ (ANOSIM: Statistic R = -0.2597, significance = 0.769). However, several low abundance bacteria were found to be significantly associated with the CO2-affected group; very few of these species are known to metabolize CO2 or are associated with CO2-rich habitats. Although this study had limitations, on a broad scale, either the CO2 flood did not impact the microbial community composition of the target formation, or microbial communities in affected wells may have reverted back to pre-injection conditions over the ca. 40 years since the CO2-EOR.}, } @article {pmid30101286, year = {2018}, author = {Gekenidis, MT and Schöner, U and von Ah, U and Schmelcher, M and Walsh, F and Drissner, D}, title = {Tracing back multidrug-resistant bacteria in fresh herb production: from chive to source through the irrigation water chain.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {11}, pages = {}, pmid = {30101286}, issn = {1574-6941}, abstract = {Environmental antibiotic-resistant bacteria (ARB) can be transferred to humans through foods. Fresh produce in particular is an ideal vector due to frequent raw consumption. A major contamination source of fresh produce is irrigation water. We hypothesized that water quality significantly affects loads of ARB and their diversity on fresh produce despite various other contamination sources present under agricultural practice conditions. Chive irrigated from an open-top reservoir or sterile-filtered water (control) was examined. Heterotrophic plate counts (HPC) and ARB were determined for water and chive with emphasis on Escherichia coli and Enterococcus spp. High HPC of freshly planted chive decreased over time and were significantly lower on control- vs. reservoir-irrigated chive at harvest (1.3 log (CFU/g) lower). Ciprofloxacin- and ceftazidime-resistant bacteria were significantly lower on control-irrigated chive at harvest and end of shelf life (up to 1.8 log (CFU/g) lower). Escherichia coli and Enterococcus spp. repeatedly isolated from water and chive proved resistant to up to six or four antibiotic classes (80% or 49% multidrug-resistant, respectively). Microbial source tracking identified E. coli-ST1056 along the irrigation chain and on chive. Whole-genome sequencing revealed that E. coli-ST1056 from both environments were clonal and carried the same transmissible multidrug-resistance plasmid, proving water as source of chive contamination. These findings emphasize the urgent need for guidelines concerning ARB in irrigation water and development of affordable water disinfection technologies to diminish ARB on irrigated produce.}, } @article {pmid30100954, year = {2018}, author = {Younkin, K and Romano, C}, title = {Student-Centered Microbioassay Laboratory Activity Utilizing Bioluminescent Bacteria.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30100954}, issn = {1935-7877}, abstract = {Student-centered teaching allows students to be actively engaged in hands-on, minds-on activities that emphasize creativity and collaboration, enabling them to ask questions and design their own investigations to real-world problems. One such problem is water contamination, which causes human health and environmental issues. However, chemical water quality testing for pollutants can be timely and expensive. In addition to chemical testing, researchers have developed assays using unicellular organisms to determine which pollutants are present and in what concentrations. In this three-hour laboratory activity, high school students and undergraduate biology or microbiology students work in pairs to help a fictional company develop a water quality microbioassay. Students design their own laboratory protocols to test the reaction of a bioluminescent bacterial species (i.e., Photobacterium phosphoreum or Aliivibrio fischeri) to exposure of common aquatic pollutants such as fertilizer, household cleaners, and motor oil. During this laboratory activity, students apply previously learned components of experimental design, including positive and negative controls, constants, and experimental groups. In addition, students gain experience writing a scientific explanation for a recommendation regarding the bioluminescent bacteria's suitability in a bioassay. Pre- and post-evaluation data revealed that students were successful in achieving the activity's objectives as well as in designing their investigations and writing their protocols using scaffolds within the lesson.}, } @article {pmid30100953, year = {2018}, author = {Bauler, TJ and Cole, S and Gibb, T and Van Enk, R and Lutwick, L and Dickinson, BL}, title = {HIV/AIDS: A Case-Based Learning Module for First-Year Medical Students.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30100953}, issn = {1935-7877}, abstract = {In medical and healthcare-related education, case-based learning (CBL) is a teaching strategy that uses clinical cases to engage students in active learning using course concepts to solve important problems. Here we describe the design and implementation of a CBL module to teach first year medical students about the human immunodeficiency virus (HIV), acute retroviral syndrome, clinical progression to acquired immunodeficiency syndrome, HIV diagnostics, assays used to assess stage of disease and response to antiretroviral treatment, and highly active antiretroviral therapy. A team of basic science and clinical faculty in the disciplines of microbiology, immunology, infection prevention and control, clinical medicine, pharmacology, and medical ethics collaboratively designed the CBL module. The results of a questionnaire indicated that the students found the CBL case interesting, engaging, and a useful educational strategy for linking basic science concepts to important clinical problems. In our experience, the CBL promoted student synthesis of basic science concepts across disciplines and engaged learners in the application of basic science knowledge to address significant real-world clinical problems.}, } @article {pmid30100952, year = {2018}, author = {Andrews, SE and Aikens, ML}, title = {Life Science Majors' Math-Biology Task Values Relate to Student Characteristics and Predict the Likelihood of Taking Quantitative Biology Courses.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30100952}, issn = {1935-7877}, abstract = {Expectancy-value theory of achievement motivation predicts that students' task values, which include their interest in and enjoyment of a task, their perceptions of the usefulness of a task (utility value), and their perceptions of the costs of engaging in the task (e.g., extra effort, anxiety), influence their achievement and academic-related choices. Further, these task values are theorized to be informed by students' sociocultural background. Although biology students are often considered to be math-averse, there is little empirical evidence of students' values of mathematics in the context of biology (math-biology task values). To fill this gap in knowledge, we sought to determine 1) life science majors' math-biology task values, 2) how math-biology task values differ according to students' sociocultural background, and 3) whether math-biology task values predict students' likelihood of taking quantitative biology courses. We surveyed life science majors about their likelihood of choosing to take quantitative biology courses and their interest in using mathematics to understand biology, the utility value of mathematics for their life science career, and the cost of doing mathematics in biology courses. Students on average reported some cost associated with doing mathematics in biology; however, they also reported high utility value and were more interested in using mathematics to understand biology than previously believed. Women and first-generation students reported more negative math-biology task values than men and continuing-generation students. Finally, students' math-biology task values predicted their likelihood of taking biomodeling and biostatistics courses. Instructional strategies promoting positive math-biology task values could be particularly beneficial for women and first-generation students, increasing the likelihood that students would choose to take advanced quantitative biology courses.}, } @article {pmid30100951, year = {2018}, author = {Gammerdinger, WJ and Kocher, TD}, title = {Understanding Student Perceptions and Practices for Pre-Lecture Content Reading in the Genetics Classroom.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {30100951}, issn = {1935-7877}, abstract = {Many faculty members assign textbook readings prior to their traditional lectures. In this study, we assessed students' level of class preparedness and surveyed their textbook reading practices weekly along with entrance and exit surveys concerning their attitudes toward reading the textbook. We report that pre-lecture reading is a significant variable in explaining pre-lecture preparedness as well as exam scores. We also report the reasons participants cited for not reading more of the textbook. We hope this analysis will allow educators to have a better understanding of the level of pre-lecture reading that is occurring in a traditional lecture-style course and the impacts of pre-lecture reading on student success.}, } @article {pmid30100950, year = {2018}, author = {}, title = {Correction Notice: Twitter as a Tool for Teaching and Communicating Microbiology: The #microMOOCSEM Initiative.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, doi = {10.1128/jmbe.v19i2.1644}, pmid = {30100950}, issn = {1935-7877}, abstract = {[This corrects the article on p. 492 in vol. 17, PMID: 28101285.].}, } @article {pmid30100389, year = {2018}, author = {Devitt, M}, title = {Historical biological essentialism.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {71}, number = {}, pages = {1-7}, doi = {10.1016/j.shpsc.2018.05.004}, pmid = {30100389}, issn = {1879-2499}, mesh = {*Biology ; *Classification ; Humans ; *Philosophy ; *Social Identification ; }, } @article {pmid30100203, year = {2018}, author = {Hung, TM and Clapham, HE and Bettis, AA and Cuong, HQ and Thwaites, GE and Wills, BA and Boni, MF and Turner, HC}, title = {The Estimates of the Health and Economic Burden of Dengue in Vietnam.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {904-918}, pmid = {30100203}, issn = {1471-5007}, support = {//Wellcome Trust/United Kingdom ; 089276/B/09/7//Wellcome Trust/United Kingdom ; 098511/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Dengue/*economics/*epidemiology ; Humans ; Quality-Adjusted Life Years ; Research/trends ; Vietnam/epidemiology ; }, abstract = {Dengue has been estimated to cause a substantial health and economic burden in Vietnam. The most recent studies have estimated that it is responsible for 39884 disability-adjusted life years (DALYs) annually, representing an economic burden of US$94.87 million per year (in 2016 prices). However, there are alternative burden estimates that are notably lower. This variation is predominantly due to differences in how the number of symptomatic dengue cases is estimated. Understanding the methodology of these burden calculations is vital when interpreting health economic analyses of dengue. This review aims to provide an overview of the health and economic burden estimates of dengue in Vietnam. We also highlight important research gaps for future studies.}, } @article {pmid30099809, year = {2018}, author = {Scott-Phillips, T and Blancke, S and Heintz, C}, title = {Four misunderstandings about cultural attraction.}, journal = {Evolutionary anthropology}, volume = {27}, number = {4}, pages = {162-173}, doi = {10.1002/evan.21716}, pmid = {30099809}, issn = {1520-6505}, mesh = {Anthropology ; Biological Evolution ; Cognition/*physiology ; Computer Simulation ; *Cultural Evolution ; *Culture ; Humans ; }, abstract = {Cultural attraction theory (CAT) is a research agenda the purpose of which is to develop causal explanations of cultural phenomena. CAT is also an evolutionary approach to culture, in the sense that it treats culture as a population of items of different types, with the frequency of tokens of those types changing over time. Now more than 20 years old, CAT has made many positive contributions, theoretical and empirical, to the naturalization of the social sciences. In consequence of this growing impact, CAT has, in recent years, been the subject of critical discussion. Here, we review and respond to these critiques. In so doing, we also provide a clear and concise introduction to CAT. We give clear characterizations of CAT's key theoretical notions, and we outline how these notions are derived from consideration of the natural character of cultural phenomena (Box). This naturalistic quality distinguishes CAT from other evolutionary approaches to culture.}, } @article {pmid30099807, year = {2018}, author = {Eisen, KE and Geber, MA}, title = {Ecological sorting and character displacement contribute to the structure of communities of Clarkia species.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1440-1458}, doi = {10.1111/jeb.13365}, pmid = {30099807}, issn = {1420-9101}, support = {1256288//Division of Environmental Biology/ ; 1650441//Division of Graduate Education/ ; //Cornell University/ ; }, abstract = {Despite long-standing interest in the evolutionary ecology of plants that share pollinators, few studies have explored how these interactions may affect communities during both community assembly (ecological sorting) and through ongoing, in situ evolution (character displacement), and how the effects of these interactions may change with community context. To determine if communities display patterns consistent with ecological sorting, we assessed the frequency of co-occurrence of four species of Clarkia in the southern Sierra foothills (Kern County, CA, USA). To investigate potential character displacement, we measured pollination-related traits on plants grown in a greenhouse common garden from seed collected in communities with one, two or four Clarkia species. Among the four species of Clarkia in this region, the two species that are often found in multi-species communities also co-occur with one another more frequently than expected under a null model. This pattern is consistent with ecological sorting, although further investigation is needed to determine the role of pollinators in shaping community assembly. Patterns of trait variation in a common garden suggest that these two species have diverged in floral traits and converged in flowering time where they co-occur, which is consistent with character displacement. Trait variation across community types also suggests that the process and outcome of character displacement may vary with community context. Because community context appears to affect both the direction and magnitude of character displacement, change in more species-rich communities may not be predictable from patterns of change in simpler communities.}, } @article {pmid30099590, year = {2018}, author = {Akoopie, A and Müller, UF}, title = {Cotranscriptional 3'-End Processing of T7 RNA Polymerase Transcripts by a Smaller HDV Ribozyme.}, journal = {Journal of molecular evolution}, volume = {86}, number = {7}, pages = {425-430}, pmid = {30099590}, issn = {1432-1432}, support = {NNX13AJ09G//National Aeronautics and Space Administration/ ; GAANN P200A150251//U.S. Department of Education/ ; }, abstract = {In vitro run-off transcription by T7 RNA polymerase generates heterogeneous 3'-ends because the enzyme tends to add untemplated adenylates. To generate homogeneous 3'-termini, HDV ribozymes have been used widely. Their sequences are added to the 3'-terminus such that co-transcriptional self-cleavage generates homogeneous 3'-ends. A shorter HDV sequence that cleaves itself efficiently would be advantageous. Here we show that a recently discovered, small HDV ribozyme is a good alternative to the previously used HDV ribozyme. The new HDV ribozyme is more efficient in some sequence contexts, and less efficient in other sequence contexts than the previously used HDV ribozyme. The smaller size makes the new HDV ribozyme a good alternative for transcript 3'-end processing.}, } @article {pmid30099551, year = {2018}, author = {Gerdol, M and Cervelli, M and Oliverio, M and Modica, MV}, title = {Piercing Fishes: Porin Expansion and Adaptation to Hematophagy in the Vampire Snail Cumia reticulata.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2654-2668}, pmid = {30099551}, issn = {1537-1719}, abstract = {Cytolytic pore-forming proteins are widespread in living organisms, being mostly involved in both sides of the host-pathogen interaction, either contributing to the innate defense or promoting infection. In venomous organisms, such as spiders, insects, scorpions, and sea anemones, pore-forming proteins are often secreted as key components of the venom. Coluporins are pore-forming proteins recently discovered in the Mediterranean hematophagous snail Cumia reticulata (Colubrariidae), highly expressed in the salivary glands that discharge their secretion at close contact with the host. To understand their putative functional role, we investigated coluporins' molecular diversity and evolutionary patterns. Coluporins is a well-diversified family including at least 30 proteins, with an overall low sequence similarity but sharing a remarkably conserved actinoporin-like predicted structure. Tracking the evolutionary history of the molluscan porin genes revealed a scattered distribution of this family, which is present in some other lineages of predatory gastropods, including venomous conoidean snails. Comparative transcriptomic analyses highlighted the expansion of porin genes as a lineage-specific feature of colubrariids. Coluporins seem to have evolved from a single ancestral porin gene present in the latest common ancestor of all Caenogastropoda, undergoing massive expansion and diversification in this colubrariid lineage through repeated gene duplication events paired with widespread episodic positive selection. As for other parasites, these findings are congruent with a "one-sided arms race," equipping the parasite with multiple variants in order to broaden its host spectrum. Overall, our results pinpoint a crucial adaptive role for coluporins in the evolution of the peculiar trophic ecology of vampire snails.}, } @article {pmid30099533, year = {2018}, author = {Jiang, X and Tang, H and Mohammed Ismail, W and Lynch, M}, title = {A Maximum-Likelihood Approach to Estimating the Insertion Frequencies of Transposable Elements from Population Sequencing Data.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2560-2571}, pmid = {30099533}, issn = {1537-1719}, support = {R01 GM101672/GM/NIGMS NIH HHS/United States ; R35 GM122566/GM/NIGMS NIH HHS/United States ; }, abstract = {Transposable elements (TEs) contribute to a large fraction of the expansion of many eukaryotic genomes due to the capability of TEs duplicating themselves through transposition. A first step to understanding the roles of TEs in a eukaryotic genome is to characterize the population-wide variation of TE insertions in the species. Here, we present a maximum-likelihood (ML) method for estimating allele frequencies and detecting selection on TE insertions in a diploid population, based on the genotypes at TE insertion sites detected in multiple individuals sampled from the population using paired-end (PE) sequencing reads. Tests of the method on simulated data show that it can accurately estimate the allele frequencies of TE insertions even when the PE sequencing is conducted at a relatively low coverage (=5X). The method can also detect TE insertions under strong selection, and the detection ability increases with sample size in a population, although a substantial fraction of actual TE insertions under selection may be undetected. Application of the ML method to genomic sequencing data collected from a natural Daphnia pulex population shows that, on the one hand, most (>90%) TE insertions present in the reference D. pulex genome are either fixed or nearly fixed (with allele frequencies >0.95); on the other hand, among the nonreference TE insertions (i.e., those detected in some individuals in the population but absent from the reference genome), the majority (>70%) are still at low frequencies (<0.1). Finally, we detected a substantial fraction (∼9%) of nonreference TE insertions under selection.}, } @article {pmid30099520, year = {2018}, author = {Adam, DC and Scotch, M and MacIntyre, CR}, title = {Bayesian Phylogeography and Pathogenic Characterization of Smallpox Based on HA, ATI, and CrmB Genes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2607-2617}, pmid = {30099520}, issn = {1537-1719}, abstract = {Variola virus is at risk of re-emergence either through accidental release, bioterrorism, or synthetic biology. The use of phylogenetics and phylogeography to support epidemic field response is expected to grow as sequencing technology becomes miniaturized, cheap, and ubiquitous. In this study, we aimed to explore the use of common VARV diagnostic targets hemagglutinin (HA), cytokine response modifier B (CrmB), and A-type inclusion protein (ATI) for phylogenetic characterization as well as the representativeness of modelling strategies in phylogeography to support epidemic response should smallpox re-emerge. We used Bayesian discrete-trait phylogeography using the most complete data set currently available of whole genome (n = 51) and partially sequenced (n = 20) VARV isolates. We show that multilocus models combining HA, ATI, and CrmB genes may represent a useful heuristic to differentiate between VARV Major and subclades of VARV Minor which have been associated with variable case-fatality rates. Where whole genome sequencing is unavailable, phylogeography models of HA, ATI, and CrmB may provide preliminary but uncertain estimates of transmission, while supplementing whole genome models with additional isolates sequenced only for HA can improve sample representativeness, maintaining similar support for transmission relative to whole genome models. We have also provided empirical evidence delineating historic international VARV transmission using phylogeography. Due to the persistent threat of re-emergence, our results provide important research for smallpox epidemic preparedness in the posteradication era as recommended by the World Health Organisation.}, } @article {pmid30099499, year = {2018}, author = {Schlub, TE and Buchmann, JP and Holmes, EC}, title = {A Simple Method to Detect Candidate Overlapping Genes in Viruses Using Single Genome Sequences.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2572-2581}, pmid = {30099499}, issn = {1537-1719}, abstract = {Overlapping genes in viruses maximize the coding capacity of their genomes and allow the generation of new genes without major increases in genome size. Despite their importance, the evolution and function of overlapping genes are often not well understood, in part due to difficulties in their detection. In addition, most bioinformatic approaches for the detection of overlapping genes require the comparison of multiple genome sequences that may not be available in metagenomic surveys of virus biodiversity. We introduce a simple new method for identifying candidate functional overlapping genes using single virus genome sequences. Our method uses randomization tests to estimate the expected length of open reading frames and then identifies overlapping open reading frames that significantly exceed this length and are thus predicted to be functional. We applied this method to 2548 reference RNA virus genomes and find that it has both high sensitivity and low false discovery for genes that overlap by at least 50 nucleotides. Notably, this analysis provided evidence for 29 previously undiscovered functional overlapping genes, some of which are coded in the antisense direction suggesting there are limitations in our current understanding of RNA virus replication.}, } @article {pmid30099482, year = {2018}, author = {Yazdi, HP and Ellegren, H}, title = {A Genetic Map of Ostrich Z Chromosome and the Role of Inversions in Avian Sex Chromosome Evolution.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2049-2060}, pmid = {30099482}, issn = {1759-6653}, mesh = {Animals ; Chromosome Inversion/*genetics ; *Chromosome Mapping ; *Evolution, Molecular ; Female ; Genetic Linkage ; Genetic Markers ; Male ; Recombination, Genetic ; Sex Chromosomes/*genetics ; Struthioniformes/*genetics ; }, abstract = {Recombination arrest is a necessary step for the evolution of distinct sex chromosomes. Structural changes, such as inversions, may represent the mechanistic basis for recombination suppression and comparisons of the structural organization of chromosomes as given by chromosome-level assemblies offer the possibility to infer inversions across species at some detail. In birds, deduction of the process of sex chromosome evolution has been hampered by the lack of a validated chromosome-level assembly from a representative of one of the two basal clades of modern birds, Paleognathae. We therefore developed a high-density genetic linkage map of the ostrich Z chromosome and used this to correct an existing assembly, including correction of a large chimeric superscaffold and the order and orientation of other superscaffolds. We identified the pseudoautosomal region as a 52 Mb segment (≈60% of the Z chromosome) where recombination occurred in both sexes. By comparing the order and location of genes on the ostrich Z chromosome with that of six bird species from the other major clade of birds (Neognathae), and of reptilian outgroup species, 25 Z-linked inversions were inferred in the avian lineages. We defined Z chromosome organization in an early avian ancestor and identified inversions spanning the candidate sex-determining DMRT1 gene in this ancestor, which could potentially have triggered the onset of avian sex chromosome evolution. We conclude that avian sex chromosome evolution has been characterized by a complex process of probably both Z-linked and W-linked inversions (and/or other processes). This study illustrates the need for validated chromosome-level assemblies for inference of genome evolution.}, } @article {pmid30099465, year = {2018}, author = {Morhardt, AC}, title = {From Fossils to Function: Integrative and Taxonomically Inclusive Approaches to Vertebrate Evolutionary Neuroscience.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {3}, pages = {123-124}, doi = {10.1159/000490745}, pmid = {30099465}, issn = {1421-9743}, } @article {pmid30099464, year = {2018}, author = {Van Essen, DC and Donahue, CJ and Glasser, MF}, title = {Development and Evolution of Cerebral and Cerebellar Cortex.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {3}, pages = {158-169}, pmid = {30099464}, issn = {1421-9743}, support = {F30 MH097312/MH/NIMH NIH HHS/United States ; R01 MH060974/MH/NIMH NIH HHS/United States ; U54 MH091657/MH/NIMH NIH HHS/United States ; P01 AG026423/AG/NIA NIH HHS/United States ; R24 NS092988/NS/NINDS NIH HHS/United States ; }, abstract = {Cerebral cortex and cerebellar cortex both vary enormously across species in their size and complexity of convolutions. We discuss the development and evolution of cortical structures in terms of anatomy and functional organization. We propose that the distinctive shapes of cerebral and cerebellar cortex can be explained by relatively few developmental processes, notably including mechanical tension along axons and dendrites. Regarding functional organization, we show how maps of myelin content in cerebral cortex are evolutionarily conserved across primates but differ in the proportion of cortex devoted to sensory, cognitive, and other functions. We summarize recent progress and challenges in (i) parcellating cerebral cortex into a mosaic of distinct areas, (ii) distinguishing cortical areas that correspond across species from those that are present in one species but not another, and (iii) using this information along with surface-based interspecies registration to gain deeper insights into cortical evolution. We also comment on the methodological challenges imposed by the differences in anatomical and functional organization of cerebellar cortex relative to cerebral cortex.}, } @article {pmid30099463, year = {2018}, author = {Gignac, PM and Kley, NJ}, title = {The Utility of DiceCT Imaging for High-Throughput Comparative Neuroanatomical Studies.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {3}, pages = {180-190}, doi = {10.1159/000485476}, pmid = {30099463}, issn = {1421-9743}, abstract = {Advancements in imaging techniques have drastically improved our ability to visualize, study, and digitally share complex, often minute, anatomical relationships. The recent adoption of soft-tissue X-ray imaging techniques, such as diffusible iodine-based contrast-enhanced computed tomography (diceCT), is beginning to offer previously unattainable insights into the detailed configurations of soft- tissue complexes across Metazoa. As a contrast agent, dissolved iodine diffuses deeply throughout preserved specimens to bind fats and carbohydrates that are natural ly present within metazoan soft tissues, increasing the radiodensities of these tissues in predictable ways. Like the current "gold standard" of magnetic resonance imaging, diceCT does not require physical dissection and can differentiate between the lipid content of myelinated versus nonmyelinated tissues, thereby offering great potential for neuroanatomical studies. Within the brain, for example, diceCT distinguishes myelinated fiber tracts from unmyelinated cortices, nuclei, and ganglia and allows three-dimensional visualization of their anatomical interrelationships at previously unrealized spatial scales. In this study, we illustrate the utility of diceCT for the rapid visualization of both external and internal brain anatomy in vertebrates - alongside the intact bones of the skull and the complete, undisturbed pathways of peripheral nerves, up to and including the target organs that they innervate. We demonstrate the transformative potential of this technique for developing high-resolution neuroanatomical datasets and describe best practices for imaging large numbers of specimens for broad evolutionary studies across vertebrates.}, } @article {pmid30099462, year = {2018}, author = {O'Brien, HD}, title = {Augmenting Trait-Dependent Diversification Estimations with Fossil Evidence: A Case Study Using Osmoregulatory Neurovasculature.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {3}, pages = {148-157}, doi = {10.1159/000488887}, pmid = {30099462}, issn = {1421-9743}, abstract = {When comparative neuromorphological studies are extended into evolutionary contexts, traits of interest are often linked to diversification patterns. Features demonstrably associated with increases in diversification rates and the infiltration or occupation of novel niche spaces are often termed "key innovations." Within the past decade, phylogenetically informed methods have been developed to test key innovation hypotheses and evaluate the influence these traits have had in shaping modern faunas. This is primarily accomplished by estimating state-dependent speciation and extinction rates. These methods have important caveats and guidelines related to both calculation and interpretation, which are necessary to understand in cases of discrete (qualitative) character analysis, as can be common when studying the evolution of neuromorphology. In such studies, inclusion of additional characters, acknowledgement of character codistribution, and addition of sister clade comparison should be explored to ensure model accuracy. Even so, phylogenies provide a survivor-only examination of character evolution, and paleontological contexts may be necessary to replicate and confirm results. Here, I review these issues in the context of selective brain cooling - a neurovascular-mediated osmoregulatory physiology that dampens hypothalamic responses to heat stress and reduces evaporative water loss in large-bodied mammals. This binary character provides an example of the interplay between sample size, evenness, and character codistribution. Moreover, it allows for an opportunity to compare phylogenetically constrained results with paleontological data, augmenting survivor-only analyses with observable extinction patterns. This trait- dependent diversification example indicates that selective brain cooling is significantly associated with the generation of modern large-mammal faunas. Importantly, paleontological data validate phylogenetic patterns and demonstrate how suites of characters worked in concert to establish the large-mammal communities of today.}, } @article {pmid30099461, year = {2018}, author = {Rilling, JK and van den Heuvel, MP}, title = {Comparative Primate Connectomics.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {3}, pages = {170-179}, doi = {10.1159/000488886}, pmid = {30099461}, issn = {1421-9743}, abstract = {A connectome is a comprehensive map of neural connections of a species nervous system. While recent work has begun comparing connectomes across a wide breadth of species, we present here a more detailed and specific comparison of connectomes across the primate order. Long-range connections are thought to improve communication efficiency and thus brain function but are costly in terms of energy and space utilization. Methods for measuring connectivity in the brain include measuring white matter volume, histological cell counting, anatomical tract tracing, diffusion-weighted imaging and tractography, and functional connectivity in MRI. Comparisons of global white matter connectivity suggest that larger primate brains are less well connected than smaller primate brains, but that humans have more connections than expected for our cortical neuron number, which may be concentrated in the prefrontal cortex. Although there is significant overlap in structural connectivity between humans and nonhuman primates, human-specific connections are found in cortical areas involved with language, imitation, and tool use. Similar to structural connectivity, there is also widespread overlap between humans and macaques in resting state functional connectivity. However, there are again a number of human-specific connections in cortical regions involved in language, tool use, and empathy. Comparative connectomics also offers the opportunity to detect specializations of connectivity in other primate species besides humans. Future research should capitalize on the ability of diffusion tractography to measure connectivity in postmortem brains that could expand the representation of species beyond humans, chimpanzees, and rhesus macaques, and facilitate identification of connectivity-based adaptations to different social and ecological niches. This work will require careful attention to establishing cortical homologies across species and to improving tractography methods to limit detection of false-positive and false-negative connections. Finally, it will be important to attempt to establish the functional significance of variation in connectivity profiles by examining how these covary with behavior and cognition both across and within species.}, } @article {pmid30099460, year = {2018}, author = {Balanoff, AM and Norell, MA and Hogan, AVC and Bever, GS}, title = {The Endocranial Cavity of Oviraptorosaur Dinosaurs and the Increasingly Complex, Deep History of the Avian Brain.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {3}, pages = {125-135}, doi = {10.1159/000488890}, pmid = {30099460}, issn = {1421-9743}, abstract = {Unraveling the origins of the character complexes diagnosing major crown clades is one of the greatest challenges in evolutionary biology. These origination events tend to optimize along extraordinarily long stem lineages where the comparative biology of extant lineages is relatively weak in its heuristic power. Here we add to a growing paleontological literature on the evolutionary origins of the modern avi an brain by describing the endocranial casts of two oviraptorosaur dinosaurs, Citipati osmolskae and Khaan mckennai. These fossil data confirm the antiquity of several avian features, including the expanded cerebrum. They also extend our appreciation of both the inherent variability in the brain-skull relationship along the avian stem and the dynamic nature of these crown characters in the earliest history of their expression.}, } @article {pmid30099459, year = {2018}, author = {Bruner, E}, title = {Human Paleoneurology and the Evolution of the Parietal Cortex.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {3}, pages = {136-147}, doi = {10.1159/000488889}, pmid = {30099459}, issn = {1421-9743}, abstract = {Paleoneurology deals with the study of brain anatomy in fossil species, as inferred from the morphology of their endocranial features. When compared with other living and extinct hominids, Homo sapiens is characterized by larger parietal bones and, according to the paleoneurological evidence, also by larger parietal lobes. The dorsal elements of the posterior parietal cortex (superior parietal lobules, precuneus, and intraparietal sulcus) may be involved in these morphological changes. This parietal expansion was also associated with an increase in the corresponding vascular networks, and possibly with increased heat loads. Only H. sapiens has a specific early ontogenetic stage in which brain form achieves such globular appearance. In adult modern humans, the precuneus displays remarkable variation, being largely responsible for the longitudinal parietal size. The precuneus is also much more expanded in modern humans than in chimpanzees. Parietal expansion is not influenced by brain size in fossil hominids or living primates. Therefore, our larger parietal cortex must be interpreted as a derived feature. Spatial models suggest that the dorsal and anterior areas of the precuneus might be involved in these derived morphological variations. These areas are crucial for visuospatial integration, and are sensitive to both genetic and environmental influences. This article reviews almost 20 years of my collaborations on human parietal lobe evolution, integrating functional craniology, paleoneurology, and evolutionary neuroanatomy.}, } @article {pmid30099063, year = {2019}, author = {Ma, X and Petrusek, A and Wolinska, J and Hu, W and Yin, M}, title = {Lineage diversity and reproductive modes of the Daphnia pulex group in Chinese lakes and reservoirs.}, journal = {Molecular phylogenetics and evolution}, volume = {130}, number = {}, pages = {424-433}, doi = {10.1016/j.ympev.2018.08.004}, pmid = {30099063}, issn = {1095-9513}, abstract = {Recent studies of the distribution and diversity of freshwater zooplankton have indicated that the previously understudied Eastern Palearctic region is an important biogeographic hotspot. Here, we explored the lineage diversity and reproductive modes of the Daphnia pulex species group across China. Members of this group are often keystone species of standing water bodies and are frequently used as a model system for ecological, evolutionary and, more recently, genomic studies. We found members of the D. pulex group in seven of seventy-six Chinese water bodies examined. We analyzed their phylogenetic position using mitochondrial markers, and explored the genetic structure of six populations using microsatellite markers. Mitochondrial DNA analysis suggested the presence of two distinct species complexes in China: the D. pulex complex that has a global distribution, and an apparently endemic Eastern Palearctic D. mitsukuri complex. Microsatellite analyses of six populations suggested that three of these reproduced by cyclical parthenogenesis, as evidenced by high clonal diversity and the absence of deviations from the Hardy-Weinberg equilibrium. In contrast, three other populations showed remarkably low diversity of multilocus genotypes. This suggests an obligate parthenogenetic reproductive mode, which was confirmed in one of the populations by comparison of genotypes of Daphnia adults and dormant embryos. All presumably obligate parthenogenetic clones were heterozygous at the majority of microsatellite loci, suggesting their hybrid origin. This was further supported by analyses of a small GTPase nuclear gene (rab4), as two alleles within single individuals belonged to different clades. Interestingly, one putatively obligate parthenogenetic clone carried three distinct alleles suggesting higher ploidy and potential gene flow between the D. pulicaria and D. mitsukuri complexes. Our data show that the expansion of the D. pulex complex in the Eastern Palearctic was associated with widespread hybridization.}, } @article {pmid30099062, year = {2018}, author = {Zembrzuski, DC and Anderson, FE}, title = {Clarifying the phylogenetic relationships and taxonomy of Stenonema, Stenacron and Maccaffertium, three common eastern North American mayfly genera.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {212-220}, doi = {10.1016/j.ympev.2018.08.002}, pmid = {30099062}, issn = {1095-9513}, abstract = {Stenonema, Stenacron, and Maccaffertium are three closely related genera of mayflies (Ephemeroptera:Heptageniidae) commonly found across North America. Due to their primarily aquatic life history and sensitivity to aquatic pollutants, these mayflies are often used as water quality indicators. However, there is little morphological variation within these genera, leading to difficulties in identification and rampant taxonomic confusion, limiting their utility as bioindicators. In an attempt to resolve the phylogenetic relationships of Stenonema, Stenacron, and Maccaffertium, and to clarify their higher-level classifications, we sequenced regions of two mitochondrial genes (cytochrome oxidase subunit 1 (cox1) and 16S ribosomal RNA (rrnl)) and two nuclear genes (Wingless (Wg) and histone H3) from 60 individuals representing most of the described species in these genera and included data from representatives of three heptageniid genera (Kageronia, Macdunnoa and Pseudiron) proposed in previous studies to be closely related to our focal taxa as well as two more distantly related heptageniid genera (Epeorus and Heptagenia) to root the phylogenies. Maximum likelihood and Bayesian analysis were conducted on single-gene and concatenated multi-gene data sets and species tree methods were utilized to resolve relationships. These analyses resolved Stenacron as a monophyletic group sister to a clade comprising Macdunnoa, Maccaffertium and Stenonema. Maccaffertium was found to be paraphyletic, with Stenonema femoratum resolved within Maccaffertium as sister to M. mexicanum. Many relationships remained unresolved or varied across analyses, making revision of the classification based on phylogenetic considerations challenging. To minimize confusion while naming clades and acknowledging uncertainty in our phylogenetic conclusions, we redefine Stenonema to include Maccaffertium and propose three subgenera-Stenonema, Maccaffertium and Lewisa- for key well-supported clades.}, } @article {pmid30098999, year = {2018}, author = {Alata Jimenez, N and Torres Pérez, SA and Sánchez-Vásquez, E and Fernandino, JI and Strobl-Mazzulla, PH}, title = {Folate deficiency prevents neural crest fate by disturbing the epigenetic Sox2 repression on the dorsal neural tube.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.08.001}, pmid = {30098999}, issn = {1095-564X}, abstract = {Folate deficiency has been known to contribute to neural tube and neural crest defects, but why these tissues are particularly affected, and which are the molecular mechanisms involved in those abnormalities are important human health questions that remain unanswered. Here we study the function of two of the main folate transporters, FolR1 and Rfc1, which are robustly expressed in these tissues. Folate is the precursor of S-adenosylmethionine, which is the main donor for DNA, protein and RNA methylation. Our results show that knockdown of FolR1 and/or Rfc1 reduced the abundance of histone H3 lysine and DNA methylation, two epigenetic modifications that play an important role during neural and neural crest development. Additionally, by knocking down folate transporter or pharmacologically inhibiting folate transport and metabolism, we observed ectopic Sox2 expression at the expense of neural crest markers in the dorsal neural tube. This is correlated with neural crest associated defects, with particular impact on orofacial formation. By using bisulfite sequencing, we show that this phenotype is consequence of reduced DNA methylation on the Sox2 locus at the dorsal neural tube, which can be rescued by the addition of folinic acid. Taken together, our in vivo results reveal the importance of folate as a source of the methyl groups necessary for the establishment of the correct epigenetic marks during neural and neural crest fate-restriction.}, } @article {pmid30098998, year = {2018}, author = {Wylie, LA and Mouillesseaux, KP and Chong, DC and Bautch, VL}, title = {Developmental SMAD6 loss leads to blood vessel hemorrhage and disrupted endothelial cell junctions.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {199-209}, doi = {10.1016/j.ydbio.2018.07.027}, pmid = {30098998}, issn = {1095-564X}, support = {R35 HL139950/HL/NHLBI NIH HHS/United States ; R01 HL043174/HL/NHLBI NIH HHS/United States ; T32 HL069768/HL/NHLBI NIH HHS/United States ; }, mesh = {Adherens Junctions/metabolism ; Animals ; Arteries/metabolism ; Blood Vessels/metabolism/*physiology ; Endothelial Cells/physiology ; Endothelium, Vascular/metabolism ; Hemorrhage/blood ; Intercellular Junctions/physiology ; Mice ; Neovascularization, Pathologic/genetics ; Neovascularization, Physiologic/genetics ; Retinal Vessels ; Signal Transduction ; Smad6 Protein/*genetics/*physiology ; }, abstract = {The BMP pathway regulates developmental processes including angiogenesis, yet its signaling outputs are complex and context-dependent. Recently, we showed that SMAD6, an intracellular BMP inhibitor expressed in endothelial cells, decreases vessel sprouting and branching both in vitro and in zebrafish. Genetic deletion of SMAD6 in mice results in poorly characterized cardiovascular defects and lethality. Here, we analyzed the effects of SMAD6 loss on vascular function during murine development. SMAD6 was expressed in a subset of blood vessels throughout development, primarily in arteries, while expression outside of the vasculature was largely confined to developing cardiac valves with no obvious embryonic phenotype. Mice deficient in SMAD6 died during late gestation and early stages of postnatal development, and this lethality was associated with vessel hemorrhage. Mice that survived past birth had increased branching and sprouting of developing postnatal retinal vessels and disorganized tight and adherens junctions. In vitro, knockdown of SMAD6 led to abnormal endothelial cell adherens junctions and increased VE-cadherin endocytosis, indicative of activated endothelium. Thus, SMAD6 is essential for proper blood vessel function during murine development, where it appears to stabilize endothelial junctions to prevent hemorrhage and aberrant angiogenesis.}, } @article {pmid30098918, year = {2018}, author = {Mather, MW and Ke, H}, title = {Novel Defense Peptides from Platelets Kill Malaria Parasites.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {729-731}, doi = {10.1016/j.pt.2018.07.013}, pmid = {30098918}, issn = {1471-5007}, abstract = {PF4 (platelet factor 4) is the first host defense peptide identified from platelets that kills malaria parasites. In a recent study, a cyclic PF4 derivative, cPF4PD, is developed, which inherits the antiparasitic effect of PF4 but excludes its potential side effects. cPF4PD is a promising novel antimalarial agent of human origin.}, } @article {pmid30098801, year = {2018}, author = {Skovmand, LH and Xu, CCY and Servedio, MR and Nosil, P and Barrett, RDH and Hendry, AP}, title = {Keystone Genes.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {689-700}, doi = {10.1016/j.tree.2018.07.002}, pmid = {30098801}, issn = {1872-8383}, abstract = {The keystone species concept is used in ecology to describe individual species with disproportionately large effects on their communities. We extend this idea to the level of genes with disproportionately large effects on ecological processes. Such 'keystone genes' (KGs) would underlie traits involved in species interactions or causing critical biotic and/or abiotic changes that influence emergent community and ecosystem properties. We propose a general framework for how KGs could be identified, while keeping KGs under the umbrella of 'ecologically important genes' (EIGs) that also include categories such as 'foundation genes', 'ecosystem engineering genes', and more. Although likely rare, KGs and other EIGs could dominate certain ecological processes; thus, their discovery and study are relevant for understanding eco-evolutionary dynamics.}, } @article {pmid30097658, year = {2018}, author = {Ye, W and Li, A}, title = {Reaction combination opens up 3D molecular diversity for drug discovery.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {314-316}, doi = {10.1038/d41586-018-05874-8}, pmid = {30097658}, issn = {1476-4687}, mesh = {*Drug Design ; *Drug Discovery ; Molecular Structure ; }, } @article {pmid30097657, year = {2018}, author = {Travaglini, KJ and Krasnow, MA}, title = {Profile of an unknown airway cell.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {313-314}, doi = {10.1038/d41586-018-05813-7}, pmid = {30097657}, issn = {1476-4687}, } @article {pmid30097656, year = {2018}, author = {Liti, G}, title = {Yeast chromosome numbers minimized using genome editing.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {317-318}, doi = {10.1038/d41586-018-05309-4}, pmid = {30097656}, issn = {1476-4687}, mesh = {Chromosomes ; *Gene Editing ; Saccharomyces cerevisiae/*genetics ; }, } @article {pmid30097655, year = {2018}, author = {Kelber, A}, title = {Birds perceive colours in categories.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {311-312}, doi = {10.1038/d41586-018-05811-9}, pmid = {30097655}, issn = {1476-4687}, } @article {pmid30097647, year = {2018}, author = {van Wolferen, M and Orell, A and Albers, SV}, title = {Archaeal biofilm formation.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {699-713}, doi = {10.1038/s41579-018-0058-4}, pmid = {30097647}, issn = {1740-1534}, abstract = {Biofilms are structured and organized communities of microorganisms that represent one of the most successful forms of life on Earth. Bacterial biofilms have been studied in great detail, and many molecular details are known about the processes that govern bacterial biofilm formation, however, archaea are ubiquitous in almost all habitats on Earth and can also form biofilms. In recent years, insights have been gained into the development of archaeal biofilms, how archaea communicate to form biofilms and how the switch from a free-living lifestyle to a sessile lifestyle is regulated. In this Review, we explore the different stages of archaeal biofilm development and highlight similarities and differences between archaea and bacteria on a molecular level. We also consider the role of archaeal biofilms in industry and their use in different industrial processes.}, } @article {pmid30097541, year = {2018}, author = {Pandey, AK and Kaur, N and Shafiq, N}, title = {Do the pharmacokinetic and pharmacodynamic graphs warrant additional explanation?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8113}, pmid = {30097541}, issn = {1091-6490}, mesh = {*Models, Biological ; }, } @article {pmid30097540, year = {2018}, author = {Kudalkar, SN and Beloor, J and Quijano, E and Spasov, KA and Lee, WG and Cisneros, JA and Saltzman, WM and Kumar, P and Jorgensen, WL and Anderson, KS}, title = {Reply to Pandey et al.: Understanding the efficacy of a potential antiretroviral drug candidate in humanized mouse model of HIV infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8114-E8115}, pmid = {30097540}, issn = {1091-6490}, support = {T32 GM007223/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-HIV Agents ; Disease Models, Animal ; *HIV Infections ; *HIV-1 ; Mice ; }, } @article {pmid30097262, year = {2018}, author = {Haelewaters, D and Hiller, T and Dick, CW}, title = {Bats, Bat Flies, and Fungi: A Case of Hyperparasitism.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {784-799}, doi = {10.1016/j.pt.2018.06.006}, pmid = {30097262}, issn = {1471-5007}, abstract = {Bats are parasitized by numerous lineages of arthropods, of which bat flies (Diptera, Nycteribiidae and Streblidae) are the most conspicuous. Bat flies themselves can be parasitized by Laboulbeniales, fungal biotrophs of arthropods. This is known as hyperparasitism, a severely understudied phenomenon. Three genera of Laboulbeniales occur on bat flies: Arthrorhynchus on Nycteribiidae, Gloeandromyces and Nycteromyces on Streblidae. In this review we introduce the parasitic partners in this tripartite system and discuss their diversity, ecology, and specificity patterns, alongside some important life history traits. Furthermore, we cover recent advances in the study of the associations between bat flies and Laboulbeniales, which were neglected for decades. Among the most immediate needs for further studies are detailed tripartite field surveys. The vermin only teaze and pinch Their foes superior by an inch So, naturalists observe, a flea Has smaller fleas that on him prey; And these have smaller still to bite 'em, And so proceed ad infinitum. Jonathan Swift (On Poetry: A Rhapsody, 1733).}, } @article {pmid30097184, year = {2018}, author = {Kuman, K and Sutton, MB and Pickering, TR and Heaton, JL}, title = {The Oldowan industry from Swartkrans cave, South Africa, and its relevance for the African Oldowan.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {52-69}, doi = {10.1016/j.jhevol.2018.06.004}, pmid = {30097184}, issn = {1095-8606}, abstract = {The oldest recognized artifacts at the Swartkrans cave hominid-bearing site in South Africa have long been known to occur in the Lower Bank of Member 1, now dated with the cosmogenic nuclide burial method to ca. 1.8-2.19 Ma. However, the affinities of this industry have been debated due to small sample size. In this paper we present newly excavated material from the Lower Bank retrieved since 2005 in the Swartkrans Paleoanthropological Research Project. The sample is now large enough to confirm its affinity with the Oldowan industrial complex. The assemblage is highly expedient and core reduction strategies are largely casual. Although freehand flaking is present, the bipolar technique is most significant, even in non-quartz raw materials. The Swartkrans assemblage shows some significant contrasts with the Sterkfontein Oldowan, ca. 2.18 Ma, which can be explained by its closer proximity to raw material sources, its somewhat different geographic context, and its more expedient nature. The Swartkrans Oldowan now provides us with the first good indication of Oldowan variability in southern Africa, where only two sizeable assemblages have thus far been discovered. Comparisons are made with other sites across Africa that help to place this variability within our overall understanding of the Oldowan industrial complex.}, } @article {pmid30097183, year = {2018}, author = {Youlatos, D and Moussa, D and Karantanis, NE and Rychlik, L}, title = {Locomotion, postures, substrate use, and foot grasping in the marsupial feathertail glider Acrobates pygmaeus (Diprotodontia: Acrobatidae): Insights into early euprimate evolution.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {148-159}, doi = {10.1016/j.jhevol.2018.07.007}, pmid = {30097183}, issn = {1095-8606}, abstract = {Debates on early euprimate evolution are related to the understanding of the ecological context that promoted their unique adaptations. Currently, these discussions mainly revolve around the habitual use of the small-branch niche or the frequent utilization of wider, and probably, strongly inclined substrates by euprimate ancestors. The current fossil evidence implies a diversity of arboreal quadrupedal behaviors for these early euprimates, associated with the use of various types of substrates. However, inferring the positional behavior of early euprimates based exclusively on fossils fails to unravel the positional flexibility in terms of modes and substrate use, which is important for understanding key adaptations related to limb postures. Following previous research, we studied the positional behavior, substrate use and pedal grasping modes of the marsupial feathertail gliders to investigate patterns of arboreal behavior that may be analogous to those exhibited by early euprimate ancestors. For the purposes of the current study, we observed and filmed 15 male and 20 female captive adult feathertail gliders Acrobates pygmaeus (Marsupialia: Diprotodontia: Acrobatidae) in a large enclosure in the Nocturnal Pavilion of Nowe Zoo, Poznań, Poland. Our observations demonstrated a strong preference for small and for horizontal substrates, avoidance of large and of vertical ones, a diverse positional repertoire mainly composed of quadrupedalism, clambering, climbing and gliding, the last occurring from small and oblique and vertical substrates, and the dominant use of hallucal grasping, especially on small, horizontal and oblique substrates. We thus consider that the generalized profile of A. pygmaeus could fit in a stage where the euarchontan heritage of vertical clawed activities on large substrates has decreased in favor of the use of small moderately inclined substrates efficiently negotiated by diagonal sequence quadrupedalism and handled via an apparently powerful hallucal grasp. Competent use of small substrates could have further expanded into small vertical substrates, which would progressively serve as new climbing platforms and takeoff perches for unspecialized leaping. We feel that this stage may have occurred early in euprimate evolution, as small body size likely provided the necessary behavioral flexibility to exploit various niches. Depending on alternative scenarios, it could represent that of the common ancestor of euprimates or be rooted at the base of strepsirrhine evolution. This study underscores the important of analyzing the behavior of extant models to infer the locomotor evolution of euarchontans, primates or euprimates.}, } @article {pmid30097068, year = {2018}, author = {Cen, W and Liu, J and Lu, S and Jia, P and Yu, K and Han, Y and Li, R and Luo, J}, title = {Comparative proteomic analysis of QTL CTS-12 derived from wild rice (Oryza rufipogon Griff.), in the regulation of cold acclimation and de-acclimation of rice (Oryza sativa L.) in response to severe chilling stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {163}, pmid = {30097068}, issn = {1471-2229}, support = {31460342//National Natural Science Foundation of China (CN)/ ; Guike-AA17204070//Guangxi innovation-driven development special funding project/ ; YCBZ2017012//Innovation Project of Guangxi Graduate Education/ ; YCSW2017047//Innovation Project of Guangxi Graduate Education/ ; }, abstract = {BACKGROUND: Rice (Oryza sativa L.) is a thermophilic crop vulnerable to chilling stress. However, common wild rice (Oryza rufipogon Griff.) in Guangxi (China) has the ability to tolerate chilling stress. To better understand the molecular mechanisms underlying chilling tolerance in wild rice, iTRAQ-based proteomic analysis was performed to examine CTS-12, a major chilling tolerance QTL derived from common wild rice, mediated chilling and recovery-induced differentially expressed proteins (DEPs) between the chilling-tolerant rice line DC90 and the chilling-sensitive 9311.

RESULTS: Comparative analysis identified 206 and 155 DEPs in 9311 and DC90, respectively, in response to the whole period of chilling and recovery. These DEPs were clustered into 6 functional groups in 9311 and 4 in DC90. The majority were enriched in the 'structural constituent of ribosome', 'protein-chromophore linkage', and 'photosynthesis and light harvesting' categories. Short Time-series Expression Miner (STEM) analysis revealed distinct dynamic responses of both chloroplast photosynthetic and ribosomal proteins between 9311 and DC90.

CONCLUSION: CTS-12 might mediate the dynamic response of chloroplast photosynthetic and ribosomal proteins in DC90 under chilling (cold acclimation) and recovery (de-acclimation) and thereby enhancing the chilling stress tolerance of this rice line. The identified DEPs and the involvement of CTS-12 in mediating the dynamic response of DC90 at the proteomic level illuminate and deepen the understanding of the mechanisms that underlie chilling stress tolerance in wild rice.}, } @article {pmid30097063, year = {2018}, author = {Walsh, E and Murphy, A}, title = {Investigating the causal relationship between employment and informal caregiving of the elderly.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {570}, pmid = {30097063}, issn = {1756-0500}, mesh = {Aged ; *Caregivers ; *Employment ; Family Characteristics ; Humans ; Ireland ; Patient Care ; }, abstract = {OBJECTIVE: Examining the causal relationship between employment and informal caring to date has been impeded in countries like Ireland where there is a lack of suitable panel data and/or variables for instrument construction. This paper employs propensity score matching to control for non-random selection into treatment and control groups which controls for differences in employment outcomes between carers and non-carers in Ireland using data from Quarterly National Household Survey 2009 Quarter 3. Earlier papers focus on using regression techniques which may lead to biased estimates.

RESULTS: Results suggest that differences exist between carers and non-carers with respect to their employment status in Ireland. Overall the results suggest that the effects are more significant for those providing greater hours of informal care per week than those providing fewer hours of care per week. The effects estimated in this paper are likely to be more precise as failing to account for potential biases in the relationship are likely to underestimate the true effect of caring on employment outcomes. We find that propensity score matching provides an alternative method of examining the relationship when suitable panel data and/or variables for instrument construction are not available.}, } @article {pmid30097057, year = {2018}, author = {An, SQ and Tang, JL}, title = {Diffusible signal factor signaling regulates multiple functions in the opportunistic pathogen Stenotrophomonas maltophilia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {569}, pmid = {30097057}, issn = {1756-0500}, support = {2014A002//Ba Gui Scholar Program of Guangxi Zhuang Autonomous Region of China/ ; }, mesh = {Bacterial Proteins/*physiology ; Signal Transduction ; Stenotrophomonas maltophilia/pathogenicity/*physiology ; Virulence ; Virulence Factors ; Xylella ; }, abstract = {OBJECTIVE: Stenotrophomonas maltophilia is a Gram-negative bacterium commonly isolated from nosocomial infections. Analysis of the genome of the clinical S. maltophilia isolate K279a indicates that it encodes a diffusible signal factor (DSF)-dependent cell-cell signaling mechanism that is highly similar to the system previously described in phytopathogens from the genera Xanthomonas and Xylella. Our objective was to study the function of DSF signaling in the clinical strain S. maltophilia K279a using genetic and functional genomic analyses.

RESULTS: We compared the wild-type strain with a mutant deficient in the rpfF (regulation of pathogenicity factors) gene that is essential for the synthesis of DSF. The effects of disruption of DSF signaling were pleiotropic with an impact on virulence, biofilm formation and pathogenesis. The phenotypic effects of rpfF mutation in S. maltophilia could be reversed by addition of exogenous DSF. Taken together, we demonstrate that DSF signaling regulates factors contributing to virulence, biofilm formation and motility of this important opportunistic pathogen.}, } @article {pmid30097053, year = {2018}, author = {Sinclair-McBride, K and Morelli, N and Tembulkar, S and Graber, K and Gonzalez-Heydrich, J and D'Angelo, EJ}, title = {Young children with psychotic symptoms and risk for suicidal thoughts and behaviors: a research note.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {568}, pmid = {30097053}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Child ; Female ; Humans ; Male ; Psychotic Disorders/*psychology ; Risk Factors ; *Suicidal Ideation ; Suicide, Attempted ; }, abstract = {OBJECTIVE: Suicidal thoughts and behaviors (STBs) are prevalent among youth with psychotic disorders (PD) relative to the general population. Recent research now suggests that STBs may present during the prodromal phase of the disease, or the clinical high risk (CHR) state. While this knowledge is important for the development of suicide prevention strategies in adolescent and adult populations, it remains unclear whether risk for suicide extends to children with or at risk for psychosis. The current study is an extension of previous work assessing STBs in youth across the psychosis continuum. We examine STBs in 37 CHR and PD children ages 7-13 years old, and further explore the prodromal symptom correlates of STB severity among CHR children.

RESULTS: CHR and PD children endorsed STBs with a frequency and severity similar to what is observed in older CHR and PD populations. A number of children had never previously vocalized their suicidal plans or intent. Among CHR children, Social Anhedonia and Odd Behavior or Appearance were significantly correlated with STB severity. These findings underscore the importance of screening for STBs even in young children presenting with psychotic symptoms.}, } @article {pmid30097019, year = {2018}, author = {Dotson, BR and Soltan, D and Schmidt, J and Areskoug, M and Rabe, K and Swart, C and Widell, S and Rasmusson, AG}, title = {The antibiotic peptaibol alamethicin from Trichoderma permeabilises Arabidopsis root apical meristem and epidermis but is antagonised by cellulase-induced resistance to alamethicin.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {165}, pmid = {30097019}, issn = {1471-2229}, support = {12:527//Carl Tryggers Stiftelse för Vetenskaplig Forskning/ ; 20150915//Crafoordska Stiftelsen/ ; 1283156424//Erasmus Mundus Action 2/ ; }, abstract = {BACKGROUND: Trichoderma fungi live in the soil rhizosphere and are beneficial for plant growth and pathogen resistance. Several species and strains are currently used worldwide in co-cultivation with crops as a biocontrol alternative to chemical pesticides even though little is known about the exact mechanisms of the beneficial interaction. We earlier found alamethicin, a peptide antibiotic secreted by Trichoderma, to efficiently permeabilise cultured tobacco cells. However, pre-treatment with Trichoderma cellulase made the cells resistant to subsequent alamethicin, suggesting a potential mechanism for plant tolerance to Trichoderma, needed for mutualistic symbiosis.

RESULTS: We here investigated intact sterile-grown Arabidopsis thaliana seedlings germinated in water or growth medium. These could be permeabilised by alamethicin but not if pretreated with cellulase. By following the fluorescence from the membrane-impermeable DNA-binding probe propidium iodide, we found alamethicin to mainly permeabilise root tips, especially the apical meristem and epidermis cells, but not the root cap and basal meristem cells nor cortex cells. Alamethicin permeabilisation and cellulase-induced resistance were confirmed by developing a quantitative in situ assay based on NADP-isocitrate dehydrogenase accessibility. The combined assays also showed that hyperosmotic treatment after the cellulase pretreatment abolished the induced cellulase resistance.

CONCLUSION: We here conclude the presence of cell-specific alamethicin permeabilisation, and cellulase-induced resistance to it, in root tip apical meristem and epidermis of the model organism A. thaliana. We suggest that contact between the plasma membrane and the cell wall is needed for the resistance to remain. Our results indicate a potential mode for the plant to avoid negative effects of alamethicin on plant growth and localises the point of potential damage and response. The results also open up for identification of plant genetic components essential for beneficial effects from Trichoderma on plants.}, } @article {pmid30097018, year = {2018}, author = {Gautier, F and Eliášová, K and Leplé, JC and Vondráková, Z and Lomenech, AM and Le Metté, C and Label, P and Costa, G and Trontin, JF and Teyssier, C and Lelu-Walter, MA}, title = {Repetitive somatic embryogenesis induced cytological and proteomic changes in embryogenic lines of Pseudotsuga menziesii [Mirb.].}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {164}, pmid = {30097018}, issn = {1471-2229}, support = {NA15-298//Chair of Excellence Forest Resources and Wood Uses/ ; LTC 17030//Ministry of Education, Youth and Sports of the Czech Republic/ ; }, abstract = {BACKGROUND: To explore poorly understood differences between primary and subsequent somatic embryogenic lines of plants, we induced secondary (2ry) and tertiary (3ry) lines from cotyledonary somatic embryos (SEs) of two Douglas-fir genotypes: SD4 and TD17. The 2ry lines exhibited significantly higher embryogenic potential (SE yields) than the 1ry lines initiated from zygotic embryos (SD4, 2155 vs 477; TD17, 240 vs 29 g- 1 f.w.). Moreover, we observed similar differences in yield between 2ry and 3ry lines of SD4 (2400 vs 3921 g- 1 f.w.). To elucidate reasons for differences in embryogenic potential induced by repetitive somatic embryogenesis we then compared 2ry vs 1ry and 2ry vs 3ry lines at histo-cytological (using LC-MS/MS) and proteomic levels.

RESULTS: Repetitive somatic embryogenesis dramatically improved the proliferating lines' cellular organization (genotype SD4's most strongly). Frequencies of singulated, bipolar SEs and compact polyembryogenic centers with elongated suspensors and apparently cleavable embryonal heads increased in 2ry and (even more) 3ry lines. Among 2300-2500 identified proteins, 162 and 228 were classified significantly differentially expressed between 2ry vs 1ry and 3ry vs 2ry lines, respectively, with special emphasis on "Proteolysis" and "Catabolic process" Gene Ontology categories. Strikingly, most of the significant proteins (> 70%) were down-regulated in 2ry relative to 1ry lines, but up-regulated in 3ry relative to 2ry lines, revealing a down-up pattern of expression. GO category enrichment analyses highlighted the opposite adjustments of global protein patterns, particularly for processes involved in chitin catabolism, lignin and L-phenylalanine metabolism, phenylpropanoid biosynthesis, oxidation-reduction, and response to karrikin. Sub-Network Enrichment Analyses highlighted interactions between significant proteins and both plant growth regulators and secondary metabolites after first (especially jasmonic acid, flavonoids) and second (especially salicylic acid, abscisic acid, lignin) embryogenesis cycles. Protein networks established after each induction affected the same "Plant development" and "Defense response" biological processes, but most strongly after the third cycle, which could explain the top embryogenic performance of 3ry lines.

CONCLUSIONS: This first report of cellular and molecular changes after repetitive somatic embryogenesis in conifers shows that each cycle enhanced the structure and singularization of EMs through modulation of growth regulator pathways, thereby improving the lines' embryogenic status.}, } @article {pmid30097017, year = {2018}, author = {Hou, BZ and Li, CL and Han, YY and Shen, YY}, title = {Characterization of the hot pepper (Capsicum frutescens) fruit ripening regulated by ethylene and ABA.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {162}, pmid = {30097017}, issn = {1471-2229}, support = {31672125//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Ripening of fleshy fruits has been classically defined as climacteric or non-climacteric. Both types of ripening are controlled by plant hormones, notably by ethylene in climacteric ripening and by abscisic acid (ABA) in non-climacteric ripening. In pepper (Capsicum), fruit ripening has been widely classified as non-climacteric, but the ripening of the hot pepper fruit appears to be climacteric. To date, how to regulate the hot pepper fruit ripening through ethylene and ABA remains unclear.

RESULTS: Here, we examined ripening of the hot pepper (Capsicum frutescens) fruit during large green (LG), initial colouring (IC), brown (Br), and full red (FR) stages. We found a peak of ethylene emission at the IC stage, followed by a peak respiratory quotient at the Br stage. By contrast, ABA levels increased slowly before the Br stage, then increased sharply and reached a maximum level at the FR stage. Exogenous ethylene promoted colouration, but exogenous ABA did not. Unexpectedly, fluridone, an inhibitor of ABA biosynthesis, promoted colouration. RNA-sequencing data obtained from the four stages around ripening showed that ACO3 and NCED1/3 gene expression determined ethylene and ABA levels, respectively. Downregulation of ACO3 and NCED1/3 expression by virus-induced gene silencing (VIGS) inhibited and promoted colouration, respectively, as evidenced by changes in carotenoid, ABA, and ethylene levels, as well as carotenoid biosynthesis-related gene expression. Importantly, the retarded colouration in ACO3-VIGS fruits was rescued by exogenous ethylene.

CONCLUSIONS: Ethylene positively regulates the hot pepper fruit colouration, while inhibition of ABA biosynthesis promotes colouration, suggesting a role of ABA in de-greening. Our findings provide new insights into processes of fleshy fruit ripening regulated by ABA and ethylene, focusing on ethylene in carotenoid biosynthesis and ABA in chlorophyll degradation.}, } @article {pmid30097016, year = {2018}, author = {Espada, M and den Akker, SE and Maier, T and Vijayapalani, P and Baum, T and Mota, M and Jones, JT}, title = {Correction to: STATAWAARS: a promoter motif associated with spatial expression in the major effector-producing tissues of the plantparasitic nematode Bursaphelenchus xylophilus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {603}, pmid = {30097016}, issn = {1471-2164}, abstract = {Following publication of the original article [1], the authors reported that one of the authors' names was erroneously changed during proofing and published incorrectly. In this Correction the incorrect and correct author name are shown. The original publication of this article has been corrected.}, } @article {pmid30097011, year = {2018}, author = {Koszela, J and Pham, NT and Evans, D and Mann, S and Perez-Pi, I and Shave, S and Ceccarelli, DFJ and Sicheri, F and Tyers, M and Auer, M}, title = {Real-time tracking of complex ubiquitination cascades using a fluorescent confocal on-bead assay.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {88}, pmid = {30097011}, issn = {1741-7007}, support = {089397/Z/09/Z//Wellcome Trust/United Kingdom ; MOP-126129//Canadian Institutes for Health Research/International ; J54359//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: The ubiquitin-proteasome system (UPS) controls the stability, localization and/or activity of the proteome. However, the identification and characterization of complex individual ubiquitination cascades and their modulators remains a challenge. Here, we report a broadly applicable, multiplexed, miniaturized on-bead technique for real-time monitoring of various ubiquitination-related enzymatic activities. The assay, termed UPS-confocal fluorescence nanoscanning (UPS-CONA), employs a substrate of interest immobilized on a micro-bead and a fluorescently labeled ubiquitin which, upon enzymatic conjugation to the substrate, is quantitatively detected on the bead periphery by confocal imaging.

RESULTS: UPS-CONA is suitable for studying individual enzymatic activities, including various E1, E2, and HECT-type E3 enzymes, and for monitoring multi-step reactions within ubiquitination cascades in a single experimental compartment. We demonstrate the power of the UPS-CONA technique by simultaneously following ubiquitin transfer from Ube1 through Ube2L3 to E6AP. We applied this multi-step setup to investigate the selectivity of five ubiquitination inhibitors reportedly targeting different classes of ubiquitination enzymes. Using UPS-CONA, we have identified a new activity of a small molecule E2 inhibitor, BAY 11-7082, and of a HECT E3 inhibitor, heclin, towards the Ube1 enzyme.

CONCLUSIONS: As a sensitive, quantitative, flexible, and reagent-efficient method with a straightforward protocol, UPS-CONA constitutes a powerful tool for interrogation of ubiquitination-related enzymatic pathways and their chemical modulators, and is readily scalable for large experiments.}, } @article {pmid30097007, year = {2018}, author = {Kaur, G and Pati, PK}, title = {In silico insights on diverse interacting partners and phosphorylation sites of respiratory burst oxidase homolog (Rbohs) gene families from Arabidopsis and rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {161}, pmid = {30097007}, issn = {1471-2229}, support = {DST/INSPIRE Fellowship/2010[79]//Innovation in Science Pursuit for Inspired Research (INSPIRE) Programme, Department of Science and Technology (DST), Government of India/ ; BT/PR13965/BRB/10/883/2010//Department of Biotechnology (DBT), Government of India/ ; }, abstract = {BACKGROUND: NADPH oxidase (Nox) is a critical enzyme involved in the generation of apoplastic superoxide (O2-), a type of reactive oxygen species (ROS) and hence regulate a wide range of biological functions in many organisms. Plant Noxes are the homologs of the catalytic subunit from mammalian NADPH oxidases and are known as respiratory burst oxidase homologs (Rbohs). Previous studies have highlighted their versatile roles in tackling different kind of stresses and in plant growth and development. In the current study, potential interacting partners and phosphorylation sites were predicted for Rboh proteins from two model species (10 Rbohs from Arabidopsis thaliana and 9 from Oryza sativa japonica). The present work is the first step towards in silico prediction of interacting partners and phosphorylation sites for Rboh proteins from two plant species.

RESULTS: In this work, an extensive range of potential partners (unique and common), leading to diverse functions were revealed from interaction networks and gene ontology classifications, where majority of AtRbohs and OsRbohs play role in stress-related activities, followed by cellular development. Further, 68 and 38 potential phosphorylation sites were identified in AtRbohs and OsRbohs, respectively. Their distribution, location and kinase specificities were also predicted and correlated with experimental data as well as verified with the other EF-hand containing proteins within both genomes.

CONCLUSIONS: Analysis of regulatory mechanisms including interaction with diverse partners and post-translational modifications like phosphorylation have provided insights regarding functional multiplicity of Rbohs. The bioinformatics-based workflow in the current study can be used to get insights for interacting partners and phosphorylation sites from Rbohs of other plant species.}, } @article {pmid30097006, year = {2018}, author = {Li, J and Huang, JP and Sukumaran, J and Knowles, LL}, title = {Microevolutionary processes impact macroevolutionary patterns.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {123}, pmid = {30097006}, issn = {1471-2148}, support = {1420967//Division of Ocean Sciences/International ; }, mesh = {Animals ; Biodiversity ; *Biological Evolution ; Birds/physiology ; Extinction, Biological ; Genetic Speciation ; Phylogeny ; }, abstract = {BACKGROUND: Macroevolutionary modeling of species diversification plays important roles in inferring large-scale biodiversity patterns. It allows estimation of speciation and extinction rates and statistically testing their relationships with different ecological factors. However, macroevolutionary patterns are ultimately generated by microevolutionary processes acting at population levels, especially when speciation and extinction are considered protracted instead of point events. Neglecting the connection between micro- and macroevolution may hinder our ability to fully understand the underlying mechanisms that drive the observed patterns.

RESULTS: In this simulation study, we used the protracted speciation framework to demonstrate that distinct microevolutionary scenarios can generate very similar biodiversity patterns (e.g., latitudinal diversity gradient). We also showed that current macroevolutionary models may not be able to distinguish these different scenarios.

CONCLUSIONS: Given the compounded nature of speciation and extinction rates, one needs to be cautious when inferring causal relationships between ecological factors and macroevolutioanry rates. Future studies that incorporate microevolutionary processes into current modeling approaches are in need.}, } @article {pmid30097005, year = {2018}, author = {Islam, MT and Sarker, SK and Talukder, S and Bhuyan, GS and Rahat, A and Islam, NN and Mahmud, H and Hossain, MA and Muraduzzaman, AKM and Rahman, J and Qadri, SK and Shahidullah, M and Mannan, MA and Tahura, S and Hussain, M and Saha, N and Akhter, S and Nahar, N and Begum, F and Shirin, T and Akhteruzzaman, S and Qadri, SS and Qadri, F and Mannoor, K}, title = {High resolution melting curve analysis enables rapid and reliable detection of G6PD variants in heterozygous females.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {58}, pmid = {30097005}, issn = {1471-2156}, abstract = {BACKGROUND: Like glucose-6-phosphate dehydrogenase (G6PD) deficient hemizygous males and homozygous females, heterozygous females could also manifest hemolytic crisis, neonatal hyperbilirubinemia or kernicterus upon exposure to oxidative stress induced by certain foods such as fava beans, drugs or infections. Although hemizygous males and homozygous females are easily detected by conventional G6PD enzyme assay method, the heterozygous state could be missed by the conventional methods as the mosaic population of both normal and deficient RBCs circulates in the blood. Thus the present study aimed to apply high resolution melting (HRM) curve analysis approach to see whether HRM could be used as a supplemental approach to increase the chance of detection of G6PD heterozygosity.

RESULTS: Sixty-three clinically suspected females were evaluated for G6PD status using both enzyme assay and HRM analysis. Four out of sixty-three participants came out as G6PD deficient by the enzyme assay method, whereas HRM approach could identify nine participants with G6PD variants, one homozygous and eight heterozygous. Although only three out of eight heterozygous samples had G6PD enzyme deficiency, the HRM-based heterozygous G6PD variants detection for the rest of the samples with normal G6PD enzyme activities could have significance because their newborns might fall victim to serious consequences under certain oxidative stress.

CONCLUSIONS: In addition to the G6PD enzyme assay, HRM curve analysis could be useful as a supplemental approach for detection of G6PD heterozygosity.}, } @article {pmid30097004, year = {2018}, author = {Abdul Hadi, LH and Xuan Lin, QX and Minh, TT and Loh, M and Ng, HK and Salim, A and Soong, R and Benoukraf, T}, title = {miREM: an expectation-maximization approach for prioritizing miRNAs associated with gene-set.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {299}, pmid = {30097004}, issn = {1471-2105}, support = {MOE2014-T3-1-006//Ministry of Education - Singapore/ ; 01/9/21/19/618//Biomedical Research Council/ ; }, abstract = {BACKGROUND: The knowledge of miRNAs regulating the expression of sets of mRNAs has led to novel insights into numerous and diverse cellular mechanisms. While a single miRNA may regulate many genes, one gene can be regulated by multiple miRNAs, presenting a complex relationship to model for accurate predictions.

RESULTS: Here, we introduce miREM, a program that couples an expectation-maximization (EM) algorithm to the common approach of hypergeometric probability (HP), which improves the prediction and prioritization of miRNAs from gene-sets of interest. miREM has been made available through a web-server (https://bioinfo-csi.nus.edu.sg/mirem2/) that can be accessed through an intuitive graphical user interface. The program incorporates a large compendium of human/mouse miRNA-target prediction databases to enhance prediction. Users may upload their genes of interest in various formats as an input and select whether to consider non-conserved miRNAs, amongst filtering options. Results are reported in a rich graphical interface that allows users to: (i) prioritize predicted miRNAs through a scatterplot of HP p-values and EM scores; (ii) visualize the predicted miRNAs and corresponding genes through a heatmap; and (iii) identify and filter homologous or duplicated predictions by clustering them according to their seed sequences.

CONCLUSION: We tested miREM using RNAseq datasets from two single "spiked" knock-in miRNA experiments and two double knock-out miRNA experiments. miREM predicted these manipulated miRNAs as having high EM scores from the gene set signatures (i.e. top predictions for single knock-in and double knock-out miRNA experiments). Finally, we have demonstrated that miREM predictions are either similar or better than results provided by existing programs.}, } @article {pmid30096485, year = {2018}, author = {Rossi, M and Fasel, N}, title = {The criminal association of Leishmania parasites and viruses.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {65-72}, doi = {10.1016/j.mib.2018.07.005}, pmid = {30096485}, issn = {1879-0364}, abstract = {In nature, humans infected with protozoan parasites can encounter viruses, which could alter their host immune response. The impact of viruses on human parasitic diseases remains largely unexplored due to the highly sterilized environment in experimental studies and the difficulty to draw a correlation between co-infection and pathology. Recent studies show that viral infections exacerbate pathology and promote dissemination of some Leishmania infections, based on a hyper-inflammatory reaction driven by type I interferons. Thus, not only the infecting parasite species, but also bystander viral infections could be a major determinant of the outcome of Leishmania infection. In this review, we focus on the contribution of viral co-infection to the exacerbation of leishmaniasis's pathology and its possible impact on treatment and vaccination strategies.}, } @article {pmid30096282, year = {2018}, author = {Willsey, HR and Walentek, P and Exner, CRT and Xu, Y and Lane, AB and Harland, RM and Heald, R and Santama, N}, title = {Katanin-like protein Katnal2 is required for ciliogenesis and brain development in Xenopus embryos.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {276-287}, pmid = {30096282}, issn = {1095-564X}, support = {R35 GM118183/GM/NIGMS NIH HHS/United States ; R01 GM042341/GM/NIGMS NIH HHS/United States ; R21 MH112158/MH/NIMH NIH HHS/United States ; K99 HL127275/HL/NHLBI NIH HHS/United States ; R01 DC011901/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Brain/*embryology/*metabolism ; Cell Cycle/physiology ; Cell Division/physiology ; Cilia/metabolism ; Embryo, Nonmammalian ; Embryonic Development ; Katanin/*metabolism ; Microtubules/metabolism ; Spindle Apparatus/metabolism ; Xenopus/embryology/metabolism ; Xenopus Proteins/metabolism ; }, abstract = {Microtubule remodeling is critical for cellular and developmental processes underlying morphogenetic changes and for the formation of many subcellular structures. Katanins are conserved microtubule severing enzymes that are essential for spindle assembly, ciliogenesis, cell division, and cellular motility. We have recently shown that a related protein, Katanin-like 2 (KATNAL2), is similarly required for cytokinesis, cell cycle progression, and ciliogenesis in cultured mouse cells. However, its developmental expression pattern, localization, and in vivo role during organogenesis have yet to be characterized. Here, we used Xenopus embryos to reveal that Katnal2 (1) is expressed broadly in ciliated and neurogenic tissues throughout embryonic development; (2) is localized to basal bodies, ciliary axonemes, centrioles, and mitotic spindles; and (3) is required for ciliogenesis and brain development. Since human KATNAL2 is a risk gene for autism spectrum disorders, our functional data suggest that Xenopus may be a relevant system for understanding the relationship of mutations in this gene to autism and the underlying molecular mechanisms of pathogenesis.}, } @article {pmid30095389, year = {2018}, author = {Levett, PN and Picardeau, M}, title = {International Committee on Systematics of Prokaryotes Subcommittee on the Taxonomy of Leptospiraceae. Minutes of the closed meeting, 28 November 2017, Palmerston North, New Zealand.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3362}, doi = {10.1099/ijsem.0.002961}, pmid = {30095389}, issn = {1466-5034}, support = {R13 AI133972/AI/NIAID NIH HHS/United States ; }, } @article {pmid30095388, year = {2018}, author = {Liu, Q and Xamxidin, M and Sun, C and Cheng, H and Meng, FX and Wu, YH and Wang, CS and Xu, XW}, title = {Marinobacter fuscus sp. nov., a marine bacterium of Gammaproteobacteria isolated from surface seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3156-3162}, doi = {10.1099/ijsem.0.002956}, pmid = {30095388}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Marinobacter/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative bacterium, designated NH169-3T, was isolated from a surface seawater sample of the South China Sea and subjected to a taxonomic polyphasic investigation. Strain NH169-3T was strictly aerobic, non-motile, non-spore-forming and rod-shaped. The colony was 1.0-2.0 mm in diameter after the growth on marine agar at 30 °C for 72 h. The centre of the colony was smooth, circular, convex and brown with a transparent periphery. Strain NH169-3T was able to grow at temperatures between 4-40 °C (optimum, 37 °C), pH 5.5-9.0 (pH 7.5) and with 0-12.5 % (w/v) NaCl (3.0 %). Chemotaxonomic analysis showed that the sole respiratory quinone of strain NH169-3T was ubiquinone 9; major fatty acids were C16 : 0 and C18 : 1ω9c, and major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and one unidentified glycolipid. The DNA G+C content was 52.7 mol%. The comparison of 16S rRNA gene sequences showed that strain NH169-3T was closely related to Marinobacter shengliensis SL013A34A2T with a similarity of 98.0 %. Three phylogenetic trees reconstructed with neighbour-joining, maximum-parsimony and maximum-likelihood methods using 16S rRNA gene sequences showed that strain NH169-3T was grouped into a separated branch with M. shengliensis SL013A34A2T in a clade of the genus Marinobacter and closely related to Marinobacter halophilus JCM 30472T, Marinobacter vinifirmus DSM 17747T and Marinobacter hydrocarbonoclasticus DSM 8798T. Analyses of both phenotypic and phylogenetic properties have suggested that strain NH169-3T was distinctive from species with validly published names in genus Marinobacter. Thus, strain NH169-3T (=MCCC 1K03455T=KCTC 62226T) is proposed as a novel species in genus Marinobacter with the name Marinobacter fuscus sp. nov.}, } @article {pmid30095387, year = {2018}, author = {Králová, S and Švec, P and Busse, HJ and Staňková, E and Váczi, P and Sedláček, I}, title = {Flavobacterium chryseum sp. nov. and Flavobacterium psychroterrae sp. nov., novel environmental bacteria isolated from Antarctica.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3132-3139}, doi = {10.1099/ijsem.0.002952}, pmid = {30095387}, issn = {1466-5034}, mesh = {Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Spermidine/analogs & derivatives/chemistry ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A group of rod-shaped, aerobic, Gram-stain-negative, gliding bacteria producing flexirubin-type pigment was isolated from environmental samples collected in Antarctica in 2009-2014. Phylogenetic analysis of the almost complete 16S rRNA gene sequences revealed two separated branches belonging to the genus Flavobacterium. Group I (n=8), represented by strain CCM 8826T, shared the highest sequence similarity to Flavobacterium collinsii 983-08T (98.8 %) and Flavobacterium saccharophilum DSM 1811T (98.4 %), and group II (n=4) represented by strain CCM 8827T shared the highest similarity to Flavobacterium aquidurense WB 1.1-56T (99.6 %). High genetic homogeneity of both groups, separation from each other and from phylogenetically close Flavobacterium species was verified by the rep-PCR fingerprinting method. DNA-DNA hybridization confirmed low genomic relatedness between strain CCM 8826T and F. collinsii 983-08T and F. saccharophilum DSM 1811T (18 and 28 %, respectively) and between strain CCM 8827T and F. aquidurense WB 1.1-56T (27 %). Chemotaxonomic analyses of strains CCM 8826T and CCM 8827T revealed the respiratory quinone to be MK-6, the major identified polar lipid was phosphatidylethanolamine and the predominant polyamine was sym-homospermidine. The common major fatty acids were C15 : 0 iso, C17 : 0 iso 3OH, C15 : 1 iso G, Summed Feature 3 (C16 : 1ω7c/C16 : 1ω6c), C15 : 0 iso 3OH and additionally, C15 : 0 anteiso among group II members. All analyses confirmed that strains of group I and II represent two novel species of the genus Flavobacterium, for which the names Flavobacterium chryseum sp. nov. (type strain CCM 8826T=P3160T=LMG 30615T) and Flavobacterium psychroterrae sp. nov. (type strain CCM 8827T=P3922T=LMG 30616T) are proposed.}, } @article {pmid30095293, year = {2018}, author = {McCullough, J and Frost, A and Sundquist, WI}, title = {Structures, Functions, and Dynamics of ESCRT-III/Vps4 Membrane Remodeling and Fission Complexes.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {85-109}, pmid = {30095293}, issn = {1530-8995}, support = {DP2 GM110772/GM/NIGMS NIH HHS/United States ; R01 GM112080/GM/NIGMS NIH HHS/United States ; R37 AI051174/AI/NIAID NIH HHS/United States ; }, abstract = {The endosomal sorting complexes required for transport (ESCRT) pathway mediates cellular membrane remodeling and fission reactions. The pathway comprises five core complexes: ALIX, ESCRT-I, ESCRT-II, ESCRT-III, and Vps4. These soluble complexes are typically recruited to target membranes by site-specific adaptors that bind one or both of the early-acting ESCRT factors: ALIX and ESCRT-I/ESCRT-II. These factors, in turn, nucleate assembly of ESCRT-III subunits into membrane-bound filaments that recruit the AAA ATPase Vps4. Together, ESCRT-III filaments and Vps4 remodel and sever membranes. Here, we review recent advances in our understanding of the structures, activities, and mechanisms of the ESCRT-III and Vps4 machinery, including the first high-resolution structures of ESCRT-III filaments, the assembled Vps4 enzyme in complex with an ESCRT-III substrate, the discovery that ESCRT-III/Vps4 complexes can promote both inside-out and outside-in membrane fission reactions, and emerging mechanistic models for ESCRT-mediated membrane fission.}, } @article {pmid30095292, year = {2018}, author = {Zhang, HT and Hiiragi, T}, title = {Symmetry Breaking in the Mammalian Embryo.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {405-426}, doi = {10.1146/annurev-cellbio-100617-062616}, pmid = {30095292}, issn = {1530-8995}, abstract = {We present an overview of symmetry breaking in early mammalian development as a continuous process from compaction to specification of the body axes. While earlier studies have focused on individual symmetry-breaking events, recent advances enable us to explore progressive symmetry breaking during early mammalian development. Although we primarily discuss embryonic development of the mouse, as it is the best-studied mammalian model system to date, we also highlight the shared and distinct aspects between different mammalian species. Finally, we discuss how insights gained from studying mammalian development can be generalized in light of self-organization principles. With this review, we hope to highlight new perspectives in studying symmetry breaking and self-organization in multicellular systems.}, } @article {pmid30095291, year = {2018}, author = {Hu, MM and Shu, HB}, title = {Cytoplasmic Mechanisms of Recognition and Defense of Microbial Nucleic Acids.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {357-379}, doi = {10.1146/annurev-cellbio-100617-062903}, pmid = {30095291}, issn = {1530-8995}, abstract = {Microbial nucleic acids are major signatures of invading pathogens, and their recognition by various host pattern recognition receptors (PRRs) represents the first step toward an efficient innate immune response to clear the pathogens. The nucleic acid-sensing PRRs are localized at the plasma membrane, the cytosol, and/or various cellular organelles. Sensing of nucleic acids and signaling by PRRs involve recruitment of distinct signaling components, and PRRs are intensively regulated by cellular organelle trafficking. PRR-mediated innate immune responses are also heavily regulated by posttranslational modifications, including phosphorylation, polyubiquitination, sumoylation, and glutamylation. In this review, we focus on our current understanding of recognition of microbial nucleic acid by PRRs, particularly on their regulation by organelle trafficking and posttranslational modifications. We also discuss how sensing of self nucleic acids and dysregulation of PRR-mediated signaling lead to serious human diseases.}, } @article {pmid30095166, year = {2018}, author = {Borrero-Echeverry, F and Bengtsson, M and Nakamuta, K and Witzgall, P}, title = {Plant odor and sex pheromone are integral elements of specific mate recognition in an insect herbivore.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2225-2233}, pmid = {30095166}, issn = {1558-5646}, support = {IC-E3//Sveriges Lantbruksuniversitet/ ; IC-E3//Svenska Forskningsrådet Formas/ ; }, abstract = {Specific mate recognition relies on the chemical senses in most animals, and especially in nocturnal insects. Two signal types mediate premating olfactory communication in terrestrial habitats: sex pheromones, which blend into an atmosphere of plant odorants. We show that host plant volatiles affect the perception of sex pheromone in males of the African cotton leafworm Spodoptera littoralis and that pheromone and plant volatiles are not perceived as independent messages. In clean air, S. littoralis males are attracted to single synthetic pheromone components or even the pheromone of a sibling species, oriental cotton leafworm S. litura. Presence of host plant volatiles, however, reduces the male response to deficient or heterospecific pheromone signals. That plant cues enhance discrimination of sex pheromone quality confirms the idea that specific mate recognition in noctuid moths has evolved in concert with adaptation to host plants. Shifts in either female host preference or sex pheromone biosynthesis give rise to new communication channels that have the potential to initiate or contribute to reproductive isolation.}, } @article {pmid30095165, year = {2018}, author = {Tomaszewski, CE and Kulbaba, MW and Harder, LD}, title = {Mating consequences of contrasting hermaphroditic plant sexual systems.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2114-2128}, doi = {10.1111/evo.13572}, pmid = {30095165}, issn = {1558-5646}, support = {RGPAS/429418-2012//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN/107375-2012//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {For hermaphroditic angiosperms with multiple flowers, the sex roles can be exclusively combined in bisexual flowers (monocliny), strictly separated among different flowers (monoecy), or arrayed in mixtures of bisexual flowers with female flowers (gynomonoecy) or male flowers (andromonoecy). The hypothesized benefits favoring the evolution of these contrasting hermaphroditic sexual systems are typically examined individually, usually by assessing success through only one sex role. We tested predictions of most hypotheses experimentally with an andromonoecious species, Anticlea occidentalis (Melanthiaceae), based on the performance of intact plants (andromonoecy) and those with emasculated bisexual flowers (functionally monoecious) or emasculated male flowers (functionally monoclinous with sterile peripheral flowers). Andromonoecy in this species enables efficient, size-dependent resource allocation, emphasizing female function in large plants. Emasculation revealed that anthers in male flowers promote female mating quality (outcrossing rate and mate diversity), whereas anthers in bisexual flowers promote male mating quantity (pollen dispersal distance and probability of any siring success). Thus, different hermaphroditic sexual systems likely evolve to capitalize on suites of benefits, rather than just one, and provide compromises between quantitative and qualitative reproductive components. These compromises apparently maximize an individual's combined genetic contributions through female and male functions, rather than separate contributions through each sex role.}, } @article {pmid30095156, year = {2018}, author = {Møller, AP and Erritzøe, J and van Dongen, S}, title = {Body size, developmental instability, and climate change.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2049-2056}, doi = {10.1111/evo.13570}, pmid = {30095156}, issn = {1558-5646}, abstract = {Development is often temperature-dependent. We hypothesized smaller size and larger asymmetry with increasing temperatures. However, we also predicted associations with asymmetry to differ among traits that differ in their degree of functional importance (especially the functional wings in migratory birds were predicted to be more canalized), timing of development (skeletal [femur, tarsus, and humerus] vs. feather [wing and tail traits]). We analyzed a large dataset of which we included species with at least 20 specimens resulting in 5533 asymmetry values in 1593 individuals from 66 species. There was a consistent significant decrease in size with temperature across all traits. Fluctuating asymmetry (FA) for wings and femur was on average lower, suggesting higher canalization, and it decreased with migration distance, however that was not the case for the other traits. FA increased with increasing temperature for wings, but not for the other characters, where the different responses of different characters to temperature were significant. Because there was no significant three-way interaction between temperature, migration distance, and character, the asymmetry-temperature response was similar in migratory and resident species. These findings imply that climate warming reduces size of all traits and decreases developmental instability of wings in birds.}, } @article {pmid30095155, year = {2018}, author = {Sane, M and Miranda, JJ and Agashe, D}, title = {Antagonistic pleiotropy for carbon use is rare in new mutations.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2202-2213}, pmid = {30095155}, issn = {1558-5646}, support = {//National Centre for Biological Sciences/ ; //Council for Scientific and Industrial Research/ ; IA/I/17/1/503091//Wellcome Trust-DBT India Alliance/India ; //Wellcome Trust/United Kingdom ; IA/I/17/1/503091//Wellcome Trust/DBT-India Alliance/ ; }, abstract = {Pleiotropic effects of mutations underlie diverse biological phenomena such as ageing and specialization. In particular, antagonistic pleiotropy ("AP": when a mutation has opposite fitness effects in different environments) generates tradeoffs, which may constrain adaptation. Models of adaptation typically assume that AP is common - especially among large-effect mutations - and that pleiotropic effect sizes are positively correlated. Empirical tests of these assumptions have focused on de novo beneficial mutations arising under strong selection. However, most mutations are actually deleterious or neutral, and may contribute to standing genetic variation that can subsequently drive adaptation. We quantified the incidence, nature, and effect size of pleiotropy for carbon utilization across 80 single mutations in Escherichia coli that arose under mutation accumulation (i.e., weak selection). Although ∼46% of the mutations were pleiotropic, only 11% showed AP; among beneficial mutations, only ∼4% showed AP. In some environments, AP was more common in large-effect mutations; and AP effect sizes across environments were often negatively correlated. Thus, AP for carbon use is generally rare (especially among beneficial mutations); is not consistently enriched in large-effect mutations; and often involves weakly deleterious antagonistic effects. Our unbiased quantification of mutational effects therefore suggests that antagonistic pleiotropy may be unlikely to cause maladaptive tradeoffs.}, } @article {pmid30094969, year = {2018}, author = {Ponz-Segrelles, G and Bleidorn, C and Aguado, MT}, title = {Expression of vasa, piwi, and nanos during gametogenesis in Typosyllis antoni (Annelida, Syllidae).}, journal = {Evolution & development}, volume = {20}, number = {5}, pages = {132-145}, doi = {10.1111/ede.12263}, pmid = {30094969}, issn = {1525-142X}, support = {CGL2015-63593-P//Ministerio de Economía y Competitividad/International ; }, mesh = {Animals ; DEAD-box RNA Helicases/*genetics ; Female ; *Gametogenesis ; Male ; Phylogeny ; Polychaeta/classification/*genetics/physiology ; RNA-Binding Proteins/*genetics ; }, abstract = {Although model species have proven to be crucial for developmental biology, the evo-devo approach requires a broader picture across phylogeny. Herein, we try to expand the range of studied annelids by presenting a transcriptome of Typosyllis antoni as a tool for the study of developmental and evolutionary processes in Syllidae. Moreover, we provide homologs of the stem-cell markers vasa, piwi, and nanos, and investigate their expression patterns in gamete-producing individuals for the first time in this group. We found no expression in females, while there is a distinct expression pattern in males. Based on this data, we argue that spermatogenesis starts in the gonads and finishes in the coelomic cavity, and it occurs simultaneously in a large number of segments. Surprisingly, no expression of the stem-cell markers was found in the segment addition zone of these reproducing animals (stolonizing). Preliminary explanations like a lack of growth during stolonization, or the absence of a common genetic program between germ and somatic stem cells, are discussed. Finally, no reservoir of primordial cells has been detected, suggesting a possible epigenic origin of the Primordial Germ Cells of this species, though this hypothesis needs to be further investigated.}, } @article {pmid30094964, year = {2018}, author = {Cordero, GA and Liu, H and Wimalanathan, K and Weber, R and Quinteros, K and Janzen, FJ}, title = {Gene network variation and alternative paths to convergent evolution in turtles.}, journal = {Evolution & development}, volume = {20}, number = {5}, pages = {172-185}, doi = {10.1111/ede.12264}, pmid = {30094964}, issn = {1525-142X}, support = {DEB-1310874//NSF Doctoral Dissertation Improvement/International ; DEB-0640932//NSF/International ; DEB-1242510//NSF/International ; //Society for the Study of Evolution Rosemary Grant Graduate Student Research Award/International ; //Chicago Herpetological Society/International ; //Nebraska Herpetological Society/International ; //ISU Ecology, Evolution, and Organismal Biology/International ; //Sigma Xi/International ; //Society for Integrative and Comparative Biology/International ; }, mesh = {Animal Shells/anatomy & histology ; Animals ; *Biological Evolution ; *Gene Regulatory Networks ; Phylogeny ; Reptilian Proteins/genetics ; Turtles/*anatomy & histology/classification/*genetics/growth & development ; }, abstract = {Diversification of the turtle's shell comprises remarkable phenotypic transformations. For instance, two divergent species convergently evolved shell-closing systems with shoulder blade (scapula) segments that enable coordinated movements with the shell. We expected these unusual structures to originate via similar changes in underlying gene networks, as skeletal segment formation is an evolutionarily conserved developmental process. We tested this hypothesis by comparing transcriptomes of scapula tissue across three stages of embryonic development in three emydid turtles from natural populations. We found that alternative strategies for skeletal segmentation were associated with interspecific differences in gene co-expression networks. Notably, mesenchyme homeobox 2 (MEOX2) and HOXA3-5 were central hubs driving the activity of 2,806 genes in a candidate network for scapula segmentation, albeit in only one species. Even so, scapula muscle overgrowth corresponded to the activity of similar myogenic networks in both species. This and other derived developmental processes were not observed in the third species, which displayed the ancestral (unsegmented) scapula condition. Differential gene expression tests against this reference lineage supported histological and network analyses. Our findings illustrate that molecular underpinnings of convergent evolution, including during the diversification of the atypical turtle "body plan," are influenced by variation in underlying developmental processes.}, } @article {pmid30094953, year = {2018}, author = {Huggett, MJ and Apprill, A}, title = {Coral microbiome database: Integration of sequences reveals high diversity and relatedness of coral-associated microbes.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12686}, pmid = {30094953}, issn = {1758-2229}, support = {OCE-1233612//NSF/ ; OCE-1736288//NSF/ ; //Edith Cowan University/ ; }, abstract = {Coral-associated microorganisms are thought to play a fundamental role in the health and ecology of corals, but understanding of specific coral-microbial interactions are lacking. In order to create a framework to examine coral-microbial specificity, we integrated and phylogenetically compared 21,100 SSU rRNA gene Sanger-produced sequences from bacteria and archaea associated with corals from previous studies, and accompanying host, location and publication metadata, to produce the Coral Microbiome Database. From this database, we identified 39 described and candidate phyla of Bacteria and two Archaea phyla associated with corals, demonstrating that corals are one of the most phylogenetically diverse animal microbiomes. Secondly, this new phylogenetic resource shows that certain microorganisms are indeed specific to corals, including evolutionary distinct hosts. Specifically, we identified 2-37 putative monophyletic, coral-specific sequence clusters within bacterial genera associated with the greatest number of coral species (Vibrio, Endozoicomonas and Ruegeria) as well as functionally relevant microbial taxa ("Candidatus Amoebophilus", "Candidatus Nitrosopumilus" and under recognized cyanobacteria). This phylogenetic resource provides a framework for more targeted studies of corals and their specific microbial associates, which is timely given the escalated need to understand the role of the coral microbiome and its adaptability to changing ocean and reef conditions.}, } @article {pmid30094916, year = {2018}, author = {Filannino, P and De Angelis, M and Di Cagno, R and Gozzi, G and Riciputi, Y and Gobbetti, M}, title = {How Lactobacillus plantarum shapes its transcriptome in response to contrasting habitats.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3700-3716}, doi = {10.1111/1462-2920.14372}, pmid = {30094916}, issn = {1462-2920}, support = {//Apulian Region Project cod/ ; }, abstract = {Triplets of Lactobacullus plantarum strains were isolated from nine contrasting habitats. Without any passage through other culture media, isolation and cultivation were on model media that strictly reproduced the chemical and physical conditions and stressors of the habitats of origin. Here, we demonstrated how L. plantarum regulates and shapes its transcriptome in response to contrasting habitats. Firstly, multivariate clustering analysis of transcriptional data (RNA-Seq), complemented with metabolomics and phenomics, grouped the strains according to the habitats of origin. Subsequently, selected strains from each habitat switched to repeated cultivation on MRS medium and transcriptomes homogenized into a unique cluster. Adaptation to this common medium mainly relied on activation of genes for phage- and prophage-related proteins and transposases. Finally, the comparison of growth across model media and with respect to MRS medium showed that 44% of the overall 3112 gene transcripts changed depending on the specific habitat. Regulation and shaping of transcriptomes mainly concerned carbohydrate acquisition, pyruvate catabolism, proteolytic system and amino acid, lipid and inorganic ion transport and metabolism, with contrasting responses for contrasting habitats. Pathways reconstruction demonstrated how the large genome size of L. plantarum imparts transcriptome and metabolic flexibility as the basic mechanism for a nomadic lifestyle.}, } @article {pmid30094835, year = {2018}, author = {Li, Q and Grossenbacher, DL and Angert, AL}, title = {The effect of range overlap on ecological niche divergence depends on spatial scale in monkeyflowers.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2100-2113}, doi = {10.1111/evo.13567}, pmid = {30094835}, issn = {1558-5646}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; //Center for Population Biology at UC Davis/ ; DEB0910038//NSF-DDIG/ ; }, abstract = {Patterns of niche divergence and geographical range overlap of closely related species provide insights into the evolutionary dynamics of ecological niches. When ranges overlap, shared selective pressures may preserve niche similarity along coarse-scale macrohabitat axes (e.g., bioclimates). Alternatively, competitive interactions may drive greater divergence along local-scale microhabitat axes (e.g., micro-topographical features). We tested these hypotheses in 16 species pairs of western North American monkeyflowers (Erythranthe and Diplacus, formerly Mimulus) with estimations of species' niches, geographic ranges, and a robust phylogeny. We found that macrohabitat niche divergence decreased with increasing range overlap, consistent with convergent selection operating at a coarse scale. No significant relationship was detected for microhabitat niches. Additionally, niche divergence was greater for recently diverged pairs along all macrohabitat niche axes, but greater for distantly diverged pairs along one microhabitat axis related to vegetation cover. For species pairs with partially overlapping ranges, greater microhabitat divergence was detected in sympatry than in allopatry for at least one niche axis for three of four pairs, consistent with character displacement in sympatry. Thus, coarse- and local-scale niche divergence show dissimilar patterns in relation to range overlap and divergence time, perhaps because the relative importance of convergent versus divergent selection depends on spatial scale.}, } @article {pmid30094027, year = {2018}, author = {Long, E}, title = {Evolutionary medicine: Why does prevalence of myopia significantly increase?.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {151-152}, pmid = {30094027}, issn = {2050-6201}, } @article {pmid30093724, year = {2018}, author = {Trenkmann, M}, title = {Lessons from 1 million genomes.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {592-593}, doi = {10.1038/s41576-018-0047-5}, pmid = {30093724}, issn = {1471-0064}, } @article {pmid30093723, year = {2018}, author = {Furlong, R}, title = {FOXP2 tells a cautionary tale.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {592-593}, doi = {10.1038/s41576-018-0046-6}, pmid = {30093723}, issn = {1471-0064}, } @article {pmid30093672, year = {2018}, author = {Cross, RL}, title = {Paul Delos Boyer (1918-2018).}, journal = {Nature}, volume = {560}, number = {7718}, pages = {308}, doi = {10.1038/d41586-018-05880-w}, pmid = {30093672}, issn = {1476-4687}, } @article {pmid30093605, year = {2018}, author = {Su, Q and Hu, F and Ge, X and Lei, J and Yu, S and Wang, T and Zhou, Q and Mei, C and Shi, Y}, title = {Structure of the human PKD1-PKD2 complex.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {}, doi = {10.1126/science.aat9819}, pmid = {30093605}, issn = {1095-9203}, mesh = {Cryoelectron Microscopy ; Crystallography, X-Ray ; Humans ; Multiprotein Complexes/*chemistry/genetics/ultrastructure ; Mutation ; Polycystic Kidney, Autosomal Dominant/genetics/*metabolism ; Protein Domains ; Protein Folding ; TRPP Cation Channels/*chemistry/genetics/metabolism/ultrastructure ; }, abstract = {Mutations in two genes, PKD1 and PKD2, account for most cases of autosomal dominant polycystic kidney disease, one of the most common monogenetic disorders. Here we report the 3.6-angstrom cryo-electron microscopy structure of truncated human PKD1-PKD2 complex assembled in a 1:3 ratio. PKD1 contains a voltage-gated ion channel (VGIC) fold that interacts with PKD2 to form the domain-swapped, yet noncanonical, transient receptor potential (TRP) channel architecture. The S6 helix in PKD1 is broken in the middle, with the extracellular half, S6a, resembling pore helix 1 in a typical TRP channel. Three positively charged, cavity-facing residues on S6b may block cation permeation. In addition to the VGIC, a five-transmembrane helix domain and a cytosolic PLAT domain were resolved in PKD1. The PKD1-PKD2 complex structure establishes a framework for dissecting the function and disease mechanisms of the PKD proteins.}, } @article {pmid30093604, year = {2018}, author = {Kalhor, R and Kalhor, K and Mejia, L and Leeper, K and Graveline, A and Mali, P and Church, GM}, title = {Developmental barcoding of whole mouse via homing CRISPR.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6405}, pages = {}, pmid = {30093604}, issn = {1095-9203}, support = {P50 HG005550/HG/NHGRI NIH HHS/United States ; R01 GM123313/GM/NIGMS NIH HHS/United States ; R01 MH103910/MH/NIMH NIH HHS/United States ; R01 CA222826/CA/NCI NIH HHS/United States ; R01 HG009285/HG/NHGRI NIH HHS/United States ; }, mesh = {Alleles ; Animals ; *CRISPR-Cas Systems ; Cell Lineage ; Embryonic Development/*genetics ; Embryonic Stem Cells ; Gene Expression Profiling/*methods ; Mice ; Mutation ; RNA, Guide/genetics ; }, abstract = {In vivo barcoding using nuclease-induced mutations is a powerful approach for recording biological information, including developmental lineages; however, its application in mammalian systems has been limited. We present in vivo barcoding in the mouse with multiple homing guide RNAs that each generate hundreds of mutant alleles and combine to produce an exponential diversity of barcodes. Activation upon conception and continued mutagenesis through gestation resulted in developmentally barcoded mice wherein information is recorded in lineage-specific mutations. We used these recordings for reliable post hoc reconstruction of the earliest lineages and investigation of axis development in the brain. Our results provide an enabling and versatile platform for in vivo barcoding and lineage tracing in a mammalian model system.}, } @article {pmid30093603, year = {2018}, author = {Meng, L and Zhang, Y and Wan, X and Li, C and Zhang, X and Wang, Y and Ke, X and Xiao, Z and Ding, L and Xia, R and Yip, HL and Cao, Y and Chen, Y}, title = {Organic and solution-processed tandem solar cells with 17.3% efficiency.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6407}, pages = {1094-1098}, doi = {10.1126/science.aat2612}, pmid = {30093603}, issn = {1095-9203}, abstract = {Although organic photovoltaic (OPV) cells have many advantages, their performance still lags far behind that of other photovoltaic platforms. A fundamental reason for their low performance is the low charge mobility of organic materials, leading to a limit on the active-layer thickness and efficient light absorption. In this work, guided by a semi-empirical model analysis and using the tandem cell strategy to overcome such issues, and taking advantage of the high diversity and easily tunable band structure of organic materials, a record and certified 17.29% power conversion efficiency for a two-terminal monolithic solution-processed tandem OPV is achieved.}, } @article {pmid30093602, year = {2018}, author = {Hayes, GP and Moore, GL and Portner, DE and Hearne, M and Flamme, H and Furtney, M and Smoczyk, GM}, title = {Slab2, a comprehensive subduction zone geometry model.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6410}, pages = {58-61}, doi = {10.1126/science.aat4723}, pmid = {30093602}, issn = {1095-9203}, abstract = {Subduction zones are home to the most seismically active faults on the planet. The shallow megathrust interfaces of subduction zones host Earth's largest earthquakes and are likely the only faults capable of magnitude 9+ ruptures. Despite these facts, our knowledge of subduction zone geometry-which likely plays a key role in determining the spatial extent and ultimately the size of subduction zone earthquakes-is incomplete. We calculated the three-dimensional geometries of all seismically active global subduction zones. The resulting model, called Slab2, provides a uniform geometrical analysis of all currently subducting slabs.}, } @article {pmid30093600, year = {2018}, author = {Fyshe, A}, title = {How to start a research lab.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {618}, doi = {10.1126/science.361.6402.618}, pmid = {30093600}, issn = {1095-9203}, } @article {pmid30093599, year = {2018}, author = {Cheng, X and Ferrell, JE}, title = {Apoptosis propagates through the cytoplasm as trigger waves.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {607-612}, pmid = {30093599}, issn = {1095-9203}, support = {P50 GM107615/GM/NIGMS NIH HHS/United States ; R01 GM110564/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*physiology ; Cell-Free System ; Cytoplasm/chemistry/*physiology ; Oocytes ; *Signal Transduction ; Xenopus laevis ; }, abstract = {Apoptosis is an evolutionarily conserved form of programmed cell death critical for development and tissue homeostasis in animals. The apoptotic control network includes several positive feedback loops that may allow apoptosis to spread through the cytoplasm in self-regenerating trigger waves. We tested this possibility in cell-free Xenopus laevis egg extracts and observed apoptotic trigger waves with speeds of ~30 micrometers per minute. Fractionation and inhibitor studies implicated multiple feedback loops in generating the waves. Apoptotic oocytes and eggs exhibited surface waves with speeds of ~30 micrometers per minute, which were tightly correlated with caspase activation. Thus, apoptosis spreads through trigger waves in both extracts and intact cells. Our findings show how apoptosis can spread over large distances within a cell and emphasize the general importance of trigger waves in cell signaling.}, } @article {pmid30093598, year = {2018}, author = {Zhang, F and Zarkada, G and Han, J and Li, J and Dubrac, A and Ola, R and Genet, G and Boyé, K and Michon, P and Künzel, SE and Camporez, JP and Singh, AK and Fong, GH and Simons, M and Tso, P and Fernández-Hernando, C and Shulman, GI and Sessa, WC and Eichmann, A}, title = {Lacteal junction zippering protects against diet-induced obesity.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {599-603}, doi = {10.1126/science.aap9331}, pmid = {30093598}, issn = {1095-9203}, support = {P30 EY026878/EY/NEI NIH HHS/United States ; P01 HL107205/HL/NHLBI NIH HHS/United States ; R01 HL053793/HL/NHLBI NIH HHS/United States ; 17SDG33700124//American Heart Association-American Stroke Association/United States ; T32 HL007950/HL/NHLBI NIH HHS/United States ; R01 HL135582/HL/NHLBI NIH HHS/United States ; R01 EY025979/EY/NEI NIH HHS/United States ; T32 HL007974/HL/NHLBI NIH HHS/United States ; R01 HL125811/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD/metabolism ; Cadherins/antagonists & inhibitors/metabolism ; Chylomicrons/adverse effects/*metabolism ; Diet, High-Fat/*adverse effects ; Dietary Fats/adverse effects/*metabolism ; Enterocytes/metabolism ; Gene Deletion ; Intestinal Absorption/genetics/physiology ; Male ; Mice ; Mice, Knockout ; Neuropilin-1/*genetics ; Obesity/*etiology/*genetics ; Signal Transduction ; Vascular Endothelial Growth Factor A/antagonists & inhibitors/metabolism ; Vascular Endothelial Growth Factor Receptor-1/*genetics ; Vascular Endothelial Growth Factor Receptor-2/antagonists & inhibitors/metabolism ; }, abstract = {Excess dietary lipid uptake causes obesity, a major global health problem. Enterocyte-absorbed lipids are packaged into chylomicrons, which enter the bloodstream through intestinal lymphatic vessels called lacteals. Here, we show that preventing lacteal chylomicron uptake by inducible endothelial genetic deletion of Neuropilin1 (Nrp1) and Vascular endothelial growth factor receptor 1 (Vegfr1; also known as Flt1) renders mice resistant to diet-induced obesity. Absence of NRP1 and FLT1 receptors increased VEGF-A bioavailability and signaling through VEGFR2, inducing lacteal junction zippering and chylomicron malabsorption. Restoring permeable lacteal junctions by VEGFR2 and vascular endothelial (VE)-cadherin signaling inhibition rescued chylomicron transport in the mutant mice. Zippering of lacteal junctions by disassembly of cytoskeletal VE-cadherin anchors prevented chylomicron uptake in wild-type mice. These data suggest that lacteal junctions may be targets for preventing dietary fat uptake.}, } @article {pmid30093597, year = {2018}, author = {Young, MD and Mitchell, TJ and Vieira Braga, FA and Tran, MGB and Stewart, BJ and Ferdinand, JR and Collord, G and Botting, RA and Popescu, DM and Loudon, KW and Vento-Tormo, R and Stephenson, E and Cagan, A and Farndon, SJ and Del Castillo Velasco-Herrera, M and Guzzo, C and Richoz, N and Mamanova, L and Aho, T and Armitage, JN and Riddick, ACP and Mushtaq, I and Farrell, S and Rampling, D and Nicholson, J and Filby, A and Burge, J and Lisgo, S and Maxwell, PH and Lindsay, S and Warren, AY and Stewart, GD and Sebire, N and Coleman, N and Haniffa, M and Teichmann, SA and Clatworthy, M and Behjati, S}, title = {Single-cell transcriptomes from human kidneys reveal the cellular identity of renal tumors.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {594-599}, doi = {10.1126/science.aat1699}, pmid = {30093597}, issn = {1095-9203}, support = {MR/K023934/1//Medical Research Council/United Kingdom ; MR/M008975/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Carcinoma, Renal Cell/classification/genetics/pathology ; Child ; Genetic Variation ; Humans ; Kidney/embryology/*metabolism ; Kidney Neoplasms/classification/*genetics/*pathology ; Single-Cell Analysis ; *Transcriptome ; Wilms Tumor/classification/genetics/pathology ; }, abstract = {Messenger RNA encodes cellular function and phenotype. In the context of human cancer, it defines the identities of malignant cells and the diversity of tumor tissue. We studied 72,501 single-cell transcriptomes of human renal tumors and normal tissue from fetal, pediatric, and adult kidneys. We matched childhood Wilms tumor with specific fetal cell types, thus providing evidence for the hypothesis that Wilms tumor cells are aberrant fetal cells. In adult renal cell carcinoma, we identified a canonical cancer transcriptome that matched a little-known subtype of proximal convoluted tubular cell. Analyses of the tumor composition defined cancer-associated normal cells and delineated a complex vascular endothelial growth factor (VEGF) signaling circuit. Our findings reveal the precise cellular identities and compositions of human kidney tumors.}, } @article {pmid30093596, year = {2018}, author = {Meyer, WK and Jamison, J and Richter, R and Woods, SE and Partha, R and Kowalczyk, A and Kronk, C and Chikina, M and Bonde, RK and Crocker, DE and Gaspard, J and Lanyon, JM and Marsillach, J and Furlong, CE and Clark, NL}, title = {Ancient convergent losses of Paraoxonase 1 yield potential risks for modern marine mammals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {591-594}, doi = {10.1126/science.aap7714}, pmid = {30093596}, issn = {1095-9203}, support = {R01 HG009299/HG/NHGRI NIH HHS/United States ; T32 EB009403/EB/NIBIB NIH HHS/United States ; U54 HG008540/HG/NHGRI NIH HHS/United States ; }, mesh = {Adaptation, Biological ; Animals ; Aryldialkylphosphatase/*blood/*genetics ; *Cetacea/blood/classification/genetics ; Environmental Exposure ; *Evolution, Molecular ; Genetic Fitness ; *Lipid Metabolism ; Lipoproteins, HDL/metabolism ; Lipoproteins, LDL/metabolism ; *Metabolic Detoxication, Phase I ; Organophosphorus Compounds/*metabolism/toxicity ; Oxidation-Reduction ; Phylogeny ; Risk ; Selection, Genetic ; }, abstract = {Mammals diversified by colonizing drastically different environments, with each transition yielding numerous molecular changes, including losses of protein function. Though not initially deleterious, these losses could subsequently carry deleterious pleiotropic consequences. We have used phylogenetic methods to identify convergent functional losses across independent marine mammal lineages. In one extreme case, Paraoxonase 1 (PON1) accrued lesions in all marine lineages, while remaining intact in all terrestrial mammals. These lesions coincide with PON1 enzymatic activity loss in marine species' blood plasma. This convergent loss is likely explained by parallel shifts in marine ancestors' lipid metabolism and/or bloodstream oxidative environment affecting PON1's role in fatty acid oxidation. PON1 loss also eliminates marine mammals' main defense against neurotoxicity from specific man-made organophosphorus compounds, implying potential risks in modern environments.}, } @article {pmid30093595, year = {2018}, author = {Doctor, JN and Nguyen, A and Lev, R and Lucas, J and Knight, T and Zhao, H and Menchine, M}, title = {Opioid prescribing decreases after learning of a patient's fatal overdose.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {588-590}, doi = {10.1126/science.aat4595}, pmid = {30093595}, issn = {1095-9203}, support = {R21 AG057395/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Analgesics, Opioid/administration & dosage/*adverse effects ; Drug Overdose/*mortality ; Drug Prescriptions/*statistics & numerical data ; Female ; Humans ; Learning ; Male ; Middle Aged ; Morphine/administration & dosage/*adverse effects ; United States ; }, abstract = {Most opioid prescription deaths occur among people with common conditions for which prescribing risks outweigh benefits. General psychological insights offer an explanation: People may judge risk to be low without available personal experiences, may be less careful than expected when not observed, and may falter without an injunction from authority. To test these hypotheses, we conducted a randomized trial of 861 clinicians prescribing to 170 persons who subsequently suffered fatal overdoses. Clinicians in the intervention group received notification of their patients' deaths and a safe prescribing injunction from their county's medical examiner, whereas physicians in the control group did not. Milligram morphine equivalents in prescriptions filled by patients of letter recipients versus controls decreased by 9.7% (95% confidence interval: 6.2 to 13.2%; P < 0.001) over 3 months after intervention. We also observed both fewer opioid initiates and fewer high-dose opioid prescriptions by letter recipients.}, } @article {pmid30093594, year = {2018}, author = {Tang, HK and Leaw, JN and Rodrigues, JNB and Herbut, IF and Sengupta, P and Assaad, FF and Adam, S}, title = {The role of electron-electron interactions in two-dimensional Dirac fermions.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {570-574}, doi = {10.1126/science.aao2934}, pmid = {30093594}, issn = {1095-9203}, abstract = {The role of electron-electron interactions in two-dimensional Dirac fermion systems remains enigmatic. Using a combination of nonperturbative numerical and analytical techniques that incorporate both the contact and long-range parts of the Coulomb interaction, we identify the two previously discussed regimes: a Gross-Neveu transition to a strongly correlated Mott insulator and a semimetallic state with a logarithmically diverging Fermi velocity accurately described by the random phase approximation. We predict that experimental realizations of Dirac fermions span this crossover and that this determines whether the Fermi velocity is increased or decreased by interactions. We explain several long-standing mysteries, including why the observed Fermi velocity in graphene is consistently about 20% larger than values obtained from ab initio calculations and why graphene on different substrates shows different behaviors.}, } @article {pmid30093593, year = {2018}, author = {Jones, KR and Venter, O and Fuller, RA and Allan, JR and Maxwell, SL and Negret, PJ and Watson, JEM}, title = {Response.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {562-563}, doi = {10.1126/science.aau7317}, pmid = {30093593}, issn = {1095-9203}, } @article {pmid30093592, year = {2018}, author = {Hulme, PE}, title = {Protected land: Threat of invasive species.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {561-562}, doi = {10.1126/science.aau3784}, pmid = {30093592}, issn = {1095-9203}, mesh = {Biodiversity ; *Conservation of Natural Resources ; Ecosystem ; *Introduced Species ; }, } @article {pmid30093591, year = {2018}, author = {Gavin, MC and McCarter, J and Berkes, F and Sterling, EJ and Turner, NJ}, title = {Protected land: Many factors shape success.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {561}, doi = {10.1126/science.aau5168}, pmid = {30093591}, issn = {1095-9203}, mesh = {Biodiversity ; *Conservation of Natural Resources ; Ecosystem ; *Forestry ; }, } @article {pmid30093590, year = {2018}, author = {Lavery, JV}, title = {Building an evidence base for stakeholder engagement.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {554-556}, doi = {10.1126/science.aat8429}, pmid = {30093590}, issn = {1095-9203}, mesh = {Humans ; Policy ; Science/*trends ; *Stakeholder Participation ; }, } @article {pmid30093589, year = {2018}, author = {FitzGerald, G and Botstein, D and Califf, R and Collins, R and Peters, K and Van Bruggen, N and Rader, D}, title = {The future of humans as model organisms.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {552-553}, doi = {10.1126/science.aau7779}, pmid = {30093589}, issn = {1095-9203}, mesh = {Animal Experimentation ; Drug Evaluation, Preclinical/trends ; *Human Experimentation ; Humans ; Phenotype ; Precision Medicine/*trends ; }, } @article {pmid30093588, year = {2018}, author = {McDonald, DM}, title = {Tighter lymphatic junctions prevent obesity.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {551-552}, doi = {10.1126/science.aau5583}, pmid = {30093588}, issn = {1095-9203}, mesh = {Humans ; Intercellular Junctions ; *Lymphatic Vessels ; Obesity ; *Tight Junctions ; }, } @article {pmid30093587, year = {2018}, author = {Dames, C}, title = {Ultrahigh thermal conductivity confirmed in boron arsenide.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {549-550}, pmid = {30093587}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; 206194//Wellcome Trust/United Kingdom ; }, mesh = {*Boron ; Boron Compounds ; Surface Properties ; *Thermal Conductivity ; }, } @article {pmid30093586, year = {2018}, author = {Boczek, EE and Alberti, S}, title = {Phase changes in neurotransmission.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {548-549}, doi = {10.1126/science.aau5477}, pmid = {30093586}, issn = {1095-9203}, mesh = {*Synaptic Transmission ; }, } @article {pmid30093585, year = {2018}, author = {Palmer, M and Ruhi, A}, title = {Measuring Earth's rivers.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {546-547}, doi = {10.1126/science.aau3842}, pmid = {30093585}, issn = {1095-9203}, mesh = {*Earth (Planet) ; *Rivers ; }, } @article {pmid30093584, year = {2018}, author = {Servick, K}, title = {Control freaks.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {542-545}, doi = {10.1126/science.361.6402.542}, pmid = {30093584}, issn = {1095-9203}, mesh = {Animals ; Pest Control, Biological/*methods ; United States ; *Wasps ; }, } @article {pmid30093583, year = {2018}, author = {Leslie, M}, title = {Infrared method could safely identify cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {541}, doi = {10.1126/science.361.6402.541}, pmid = {30093583}, issn = {1095-9203}, mesh = {Animals ; Atlases as Topic ; Cells/*classification ; Humans ; *Infrared Rays ; Mice ; Spectrophotometry, Infrared/*methods ; *Synchrotrons ; }, } @article {pmid30093582, year = {2018}, author = {Pennisi, E}, title = {Hope blooms for Hawaii's iconic native tree.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {540}, doi = {10.1126/science.361.6402.540}, pmid = {30093582}, issn = {1095-9203}, mesh = {Animals ; Ascomycota/*pathogenicity ; *Conservation of Natural Resources ; Hawaii ; Livestock ; Myrtaceae/*microbiology ; Plant Diseases/*microbiology/*prevention & control ; Trees/*microbiology ; Volcanic Eruptions ; }, } @article {pmid30093581, year = {2018}, author = {Pennisi, E}, title = {Hybrids spawned Lake Victoria's rich fish diversity.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {539}, doi = {10.1126/science.361.6402.539}, pmid = {30093581}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Chimera/*genetics ; Cichlids/*genetics ; *Genetic Variation ; Hawaii ; Lakes ; Sequence Analysis, DNA ; }, } @article {pmid30093580, year = {2018}, author = {Servick, K}, title = {March of Dimes curtails support for researchers.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {538}, doi = {10.1126/science.361.6402.538}, pmid = {30093580}, issn = {1095-9203}, mesh = {Biomedical Research/*economics ; *Congenital Abnormalities ; Humans ; *Premature Birth ; *Research Support as Topic ; United States ; }, } @article {pmid30093579, year = {2018}, author = {Voosen, P}, title = {New geological age comes under fire.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {537-538}, doi = {10.1126/science.361.6402.537}, pmid = {30093579}, issn = {1095-9203}, } @article {pmid30093578, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {534-536}, doi = {10.1126/science.361.6402.534}, pmid = {30093578}, issn = {1095-9203}, } @article {pmid30093577, year = {2018}, author = {Memish, ZA}, title = {Health of the Hajj.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {533}, doi = {10.1126/science.aau9617}, pmid = {30093577}, issn = {1095-9203}, mesh = {Disease Outbreaks/*prevention & control ; Disease Transmission, Infectious/*prevention & control ; Epidemiological Monitoring ; Health ; *Human Migration ; Humans ; *Islam ; Saudi Arabia ; }, } @article {pmid30093576, year = {2018}, author = {Kippenberg, TJ and Gaeta, AL and Lipson, M and Gorodetsky, ML}, title = {Dissipative Kerr solitons in optical microresonators.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {}, doi = {10.1126/science.aan8083}, pmid = {30093576}, issn = {1095-9203}, abstract = {The development of compact, chip-scale optical frequency comb sources (microcombs) based on parametric frequency conversion in microresonators has seen applications in terabit optical coherent communications, atomic clocks, ultrafast distance measurements, dual-comb spectroscopy, and the calibration of astophysical spectrometers and have enabled the creation of photonic-chip integrated frequency synthesizers. Underlying these recent advances has been the observation of temporal dissipative Kerr solitons in microresonators, which represent self-enforcing, stationary, and localized solutions of a damped, driven, and detuned nonlinear Schrödinger equation, which was first introduced to describe spatial self-organization phenomena. The generation of dissipative Kerr solitons provide a mechanism by which coherent optical combs with bandwidth exceeding one octave can be synthesized and have given rise to a host of phenomena, such as the Stokes soliton, soliton crystals, soliton switching, or dispersive waves. Soliton microcombs are compact, are compatible with wafer-scale processing, operate at low power, can operate with gigahertz to terahertz line spacing, and can enable the implementation of frequency combs in remote and mobile environments outside the laboratory environment, on Earth, airborne, or in outer space.}, } @article {pmid30093575, year = {2018}, author = {Reich, PB and Hobbie, SE and Lee, TD and Pastore, MA}, title = {Response to Comment on "Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {}, doi = {10.1126/science.aau1300}, pmid = {30093575}, issn = {1095-9203}, mesh = {*Carbon Dioxide ; Photosynthesis ; Plant Leaves ; *Poaceae ; Soil ; }, abstract = {Wolf and Ziska suggest that soil and species attributes can explain an unexpected 20-year reversal of C3-C4 grass responses to elevated CO2 This is consistent with our original interpretation; however, we disagree with the assertion that such explanations somehow render our results irrelevant for questioning a long-standing paradigm of plant response to CO2 based on C3-C4 differences in photosynthetic pathway.}, } @article {pmid30093574, year = {2018}, author = {Wolf, J and Ziska, L}, title = {Comment on "Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {}, doi = {10.1126/science.aau1073}, pmid = {30093574}, issn = {1095-9203}, mesh = {Biomass ; *Carbon Dioxide ; Plants ; *Poaceae ; Soil ; }, abstract = {Reich et al (Reports, 20 April 2018, p. 317) assert that the responses of C3 and C4 grass biomass to elevated CO2 "challenge the current C3-C4 [elevated CO2] paradigm," but these responses can be explained by the natural history of the experimental plants and soils without challenging this paradigm.}, } @article {pmid30093390, year = {2018}, author = {Shin, JW}, title = {Squeezing cells through the epigenetic machinery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8472-8474}, pmid = {30093390}, issn = {1091-6490}, support = {R00 HL125884/HL/NHLBI NIH HHS/United States ; }, mesh = {*Epigenetic Repression ; *Epigenomics ; }, } @article {pmid30093389, year = {2018}, author = {Podgornik, R}, title = {Sticking and stacking: Persistent ordering of fragmented DNA analogs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8652-8654}, pmid = {30093389}, issn = {1091-6490}, mesh = {*DNA ; }, } @article {pmid30093388, year = {2018}, author = {Husmann, D and Lebrat, M and Häusler, S and Brantut, JP and Corman, L and Esslinger, T}, title = {Breakdown of the Wiedemann-Franz law in a unitary Fermi gas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8563-8568}, pmid = {30093388}, issn = {1091-6490}, abstract = {We report on coupled heat and particle transport measurements through a quantum point contact (QPC) connecting two reservoirs of resonantly interacting, finite temperature Fermi gases. After heating one of them, we observe a particle current flowing from cold to hot. We monitor the temperature evolution of the reservoirs and find that the system evolves after an initial response into a nonequilibrium steady state with finite temperature and chemical potential differences across the QPC. In this state any relaxation in the form of heat and particle currents vanishes. From our measurements we extract the transport coefficients of the QPC and deduce a Lorenz number violating the Wiedemann-Franz law by one order of magnitude, a characteristic persisting even for a wide contact. In contrast, the Seebeck coefficient takes a value close to that expected for a noninteracting Fermi gas and shows a smooth decrease as the atom density close to the QPC is increased beyond the superfluid transition. Our work represents a fermionic analog of the fountain effect observed with superfluid helium and poses challenges for microscopic modeling of the finite temperature dynamics of the unitary Fermi gas.}, } @article {pmid30093387, year = {2018}, author = {Yeh, SH and Hoehn, RD and Allodi, MA and Engel, GS and Kais, S}, title = {Elucidation of near-resonance vibronic coherence lifetimes by nonadiabatic electronic-vibrational state character mixing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1701390115}, pmid = {30093387}, issn = {1091-6490}, abstract = {Recent work suggests that the long-lived coherences observed in both natural and artificial light-harvesting systems (such as the Fenna-Matthews-Olson complex) could be attributed to the mixing of the pigments' electronic and vibrational degrees of freedom. To investigate the underlying mechanism of these long coherence lifetimes, a sophisticated description of interactions between the molecular aggregates and the nonequilibrium fluctuations in the surrounding environment is necessary. This is done by implementing the hierarchical equations of motion approach on model homodimers, a method used in the intermediate coupling regime for many molecular aggregates wherein the nonequilibrium environment phonons play nontrivial roles in exciton dynamics. Here we report a character change in the vibronic states-reflective of property mixing between the electronic and vibrational states-induced by an interplay between system coupling parameters within the exciton-vibrational near-resonance regime. This mixing dictates vital aspects of coherence lifetime; by tracking the degree of mixing, we are able to elucidate the relationship between coherence lifetime and both the electronic energy fluctuation and the vibrational relaxation dephasing pathways.}, } @article {pmid30093386, year = {2018}, author = {Mitra, A and Ruhnow, F and Girardo, S and Diez, S}, title = {Directionally biased sidestepping of Kip3/kinesin-8 is regulated by ATP waiting time and motor-microtubule interaction strength.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7950-E7959}, pmid = {30093386}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/*chemistry/metabolism ; Animals ; Calcium-Binding Proteins/*chemistry/genetics/metabolism ; Drosophila Proteins/*chemistry/genetics/metabolism ; Drosophila melanogaster ; Kinesin/*chemistry/genetics/metabolism ; }, abstract = {Kinesin-8 motors, which move in a highly processive manner toward microtubule plus ends where they act as depolymerases, are essential regulators of microtubule dynamics in cells. To understand their navigation strategy on the microtubule lattice, we studied the 3D motion of single yeast kinesin-8 motors, Kip3, on freely suspended microtubules in vitro. We observed short-pitch, left-handed helical trajectories indicating that kinesin-8 motors frequently switch protofilaments in a directionally biased manner. Intriguingly, sidestepping was not directly coupled to forward stepping but rather depended on the average dwell time per forward step under limiting ATP concentrations. Based on our experimental findings and numerical simulations we propose that effective sidestepping toward the left is regulated by a bifurcation in the Kip3 step cycle, involving a transition from a two-head-bound to a one-head-bound conformation in the ATP-waiting state. Results from a kinesin-1 mutant with extended neck linker hint toward a generic sidestepping mechanism for processive kinesins, facilitating the circumvention of intracellular obstacles on the microtubule surface.}, } @article {pmid30092815, year = {2018}, author = {Murali, A and Bhargava, A and Wright, ES}, title = {IDTAXA: a novel approach for accurate taxonomic classification of microbiome sequences.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {140}, pmid = {30092815}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics ; DNA Barcoding, Taxonomic/*methods ; Machine Learning ; Metagenomics/*methods ; Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Software ; }, abstract = {BACKGROUND: Microbiome studies often involve sequencing a marker gene to identify the microorganisms in samples of interest. Sequence classification is a critical component of this process, whereby sequences are assigned to a reference taxonomy containing known sequence representatives of many microbial groups. Previous studies have shown that existing classification programs often assign sequences to reference groups even if they belong to novel taxonomic groups that are absent from the reference taxonomy. This high rate of "over classification" is particularly detrimental in microbiome studies because reference taxonomies are far from comprehensive.

RESULTS: Here, we introduce IDTAXA, a novel approach to taxonomic classification that employs principles from machine learning to reduce over classification errors. Using multiple reference taxonomies, we demonstrate that IDTAXA has higher accuracy than popular classifiers such as BLAST, MAPSeq, QIIME, SINTAX, SPINGO, and the RDP Classifier. Similarly, IDTAXA yields far fewer over classifications on Illumina mock microbial community data when the expected taxa are absent from the training set. Furthermore, IDTAXA offers many practical advantages over other classifiers, such as maintaining low error rates across varying input sequence lengths and withholding classifications from input sequences composed of random nucleotides or repeats.

CONCLUSIONS: IDTAXA's classifications may lead to different conclusions in microbiome studies because of the substantially reduced number of taxa that are incorrectly identified through over classification. Although misclassification error is relatively minor, we believe that many remaining misclassifications are likely caused by errors in the reference taxonomy. We describe how IDTAXA is able to identify many putative mislabeling errors in reference taxonomies, enabling training sets to be automatically corrected by eliminating spurious sequences. IDTAXA is part of the DECIPHER package for the R programming language, available through the Bioconductor repository or accessible online (http://DECIPHER.codes).}, } @article {pmid30092779, year = {2018}, author = {Shaban, M and Ahmed, MM and Sun, H and Ullah, A and Zhu, L}, title = {Genome-wide identification of lipoxygenase gene family in cotton and functional characterization in response to abiotic stresses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {599}, pmid = {30092779}, issn = {1471-2164}, support = {2016CFA054//Natural Science Foundation of Hubei Province/ ; 2016AG001//Basic research project of the Xinjiang production and Construction Corps/ ; }, mesh = {*Gene Expression Regulation, Plant ; Genome, Plant ; Genome-Wide Association Study ; Gossypium/enzymology/*genetics ; Lipoxygenase/*genetics ; *Multigene Family ; Phylogeny ; Plant Proteins/genetics ; Stress, Physiological ; }, abstract = {BACKGROUND: Plant lipoxygenase (LOX) genes are members of the non-haeme iron-containing dioxygenase family that catalyze the oxidation of polyunsaturated fatty acids into functionally diverse oxylipins. The LOX family genes have been extensively studied under biotic and abiotic stresses, both in model and non-model plant species; however, information on their roles in cotton is still limited.

RESULTS: A total of 64 putative LOX genes were identified in four cotton species (Gossypium (G. hirsutum, G. barbadense, G. arboreum, and G. raimondii)). In the phylogenetic tree, these genes were clustered into three categories (9-LOX, 13-LOX type I, and 13-LOX type II). Segmental duplication of putative LOX genes was observed between homologues from A2 to At and D5 to Dt hinting at allopolyploidy in cultivated tetraploid species (G. hirsutum and G. barbadense). The structure and motif composition of GhLOX genes appears to be relatively conserved among the subfamilies. Moreover, many cis-acting elements related to growth, stresses, and phytohormone signaling were found in the promoter regions of GhLOX genes. Gene expression analysis revealed that all GhLOX genes were induced in at least two tissues and the majority of GhLOX genes were up-regulated in response to heat and salinity stress. Specific expressions of some genes in response to exogenous phytohormones suggest their potential roles in regulating growth and stress responses. In addition, functional characterization of two candidate genes (GhLOX12 and GhLOX13) using virus induced gene silencing (VIGS) approach revealed their increased sensitivity to salinity stress in target gene-silenced cotton. Compared with controls, target gene-silenced plants showed significantly higher chlorophyll degradation, higher H2O2, malondialdehyde (MDA) and proline accumulation but significantly reduced superoxide dismutase (SOD) activity, suggesting their reduced ability to effectively degrade accumulated reactive oxygen species (ROS).

CONCLUSION: This genome-wide study provides a systematic analysis of the cotton LOX gene family using bioinformatics tools. Differential expression patterns of cotton LOX genes in different tissues and under various abiotic stress conditions provide insights towards understanding the potential functions of candidate genes. Beyond the findings reported here, our study provides a basis for further uncovering the biological roles of LOX genes in cotton development and adaptation to stress conditions.}, } @article {pmid30092776, year = {2018}, author = {He, J and Guo, Y and Xu, J and Li, H and Fuller, A and Tait, RG and Wu, XL and Bauck, S}, title = {Comparing SNP panels and statistical methods for estimating genomic breed composition of individual animals in ten cattle breeds.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {56}, pmid = {30092776}, issn = {1471-2156}, abstract = {BACKGROUND: SNPs are informative to estimate genomic breed composition (GBC) of individual animals, but selected SNPs for this purpose were not made available in the commercial bovine SNP chips prior to the present study. The primary objective of the present study was to select five common SNP panels for estimating GBC of individual animals initially involving 10 cattle breeds (two dairy breeds and eight beef breeds). The performance of the five common SNP panels was evaluated based on admixture model and linear regression model, respectively. Finally, the downstream implication of GBC on genomic prediction accuracies was investigated and discussed in a Santa Gertrudis cattle population.

RESULTS: There were 15,708 common SNPs across five currently-available commercial bovine SNP chips. From this set, four subsets (1,000, 3,000, 5,000, and 10,000 SNPs) were selected by maximizing average Euclidean distance (AED) of SNP allelic frequencies among the ten cattle breeds. For 198 animals presented as Akaushi, estimated GBC of the Akaushi breed (GBCA) based on the admixture model agreed very well among the five SNP panels, identifying 166 animals with GBCA = 1. Using the same SNP panels, the linear regression approach reported fewer animals with GBCA = 1. Nevertheless, estimated GBCA using both models were highly correlated (r = 0.953 to 0.992). In the genomic prediction of a Santa Gertrudis population (and crosses), the results showed that the predictability of molecular breeding values using SNP effects obtained from 1,225 animals with no less than 0.90 GBC of Santa Gertrudis (GBCSG) decreased on crossbred animals with lower GBCSG.

CONCLUSIONS: Of the two statistical models used to compute GBC, the admixture model gave more consistent results among the five selected SNP panels than the linear regression model. The availability of these common SNP panels facilitates identification and estimation of breed compositions using currently-available bovine SNP chips. In view of utility, the 1 K panel is the most cost effective and it is convenient to be included as add-on content in future development of bovine SNP chips, whereas the 10 K and 16 K SNP panels can be more resourceful if used independently for imputation to intermediate or high-density genotypes.}, } @article {pmid30092775, year = {2018}, author = {Johnston, CM and Fahnøe, U and Belsham, GJ and Rasmussen, TB}, title = {Strategy for efficient generation of numerous full-length cDNA clones of classical swine fever virus for haplotyping.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {600}, pmid = {30092775}, issn = {1471-2164}, mesh = {Animals ; Classical Swine Fever/*diagnosis/genetics/virology ; Classical Swine Fever Virus/*classification/*genetics ; DNA, Complementary/*genetics ; *Genetic Techniques ; Genetic Variation ; Genotyping Techniques ; *Haplotypes ; Phylogeny ; Polymorphism, Single Nucleotide ; RNA, Viral/*genetics ; Sequence Analysis, RNA ; Swine ; }, abstract = {BACKGROUND: Direct molecular cloning of full-length cDNAs derived from viral RNA is an approach to identify the individual viral genomes within a virus population. This enables characterization of distinct viral haplotypes present during infection.

RESULTS: In this study, we recover individual genomes of classical swine fever virus (CSFV), present in a pig infected with vKos that was rescued from a cDNA clone corresponding to the highly virulent CSFV Koslov strain. Full-length cDNA amplicons (ca. 12.3 kb) were made by long RT-PCR, using RNA extracted from serum, and inserted directly into a cloning vector prior to detailed characterization of the individual viral genome sequences. The amplicons used for cloning were deep sequenced, which revealed low level sequence variation (< 5%) scattered across the genome consistent with the clone-derived origin of vKos. Numerous full-length cDNA clones were generated using these amplicons and full-genome sequencing of individual cDNA clones revealed insights into the virus diversity and the haplotypes present during infection. Most cDNA clones were unique, containing several single-nucleotide polymorphisms, and phylogenetic reconstruction revealed a low degree of order.

CONCLUSIONS: This optimized methodology enables highly efficient construction of full-length cDNA clones corresponding to individual viral genomes present within RNA virus populations.}, } @article {pmid30092770, year = {2018}, author = {Zhang, M and Han, W and Tang, H and Li, G and Zhang, M and Xu, R and Liu, Y and Yang, T and Li, W and Zou, J and Wu, K}, title = {Genomic diversity dynamics in conserved chicken populations are revealed by genome-wide SNPs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {598}, pmid = {30092770}, issn = {1471-2164}, support = {IRT_15R62//the Program for Changjiang Scholars and Innovation Research Teams in the University/ ; 973 Program, Grant 2014CB138501//the National Basic Research Program of China/ ; }, mesh = {Animals ; Chickens/*classification/*genetics ; *Genome ; Homozygote ; Inbreeding ; Linkage Disequilibrium ; *Polymorphism, Single Nucleotide ; Population Density ; Population Dynamics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Maintaining maximum genetic diversity and preserving breed viability in conserved populations necessitates the rigorous evaluation of conservation schemes. Three chicken breeds (Baier Yellow Chicken (BEC), Beijing You Chicken (BYC) and Langshan Chicken (LSC)) are currently in conservation programs in China. Changes in genetic diversity were measured by heterozygosity, genomic inbreeding coefficients, and autozygosity, using estimates derived from runs of homozygosity (ROH) that were identified using SNPs.

RESULTS: Ninety DNA samples were collected from three generations for each breed. In the most recent generation, the highest genetic diversity was observed in LSC, followed by BEC and BYC. Inbreeding coefficients based on ROH for the three breeds declined slightly between the first and middle generations, and then rapidly increased. No inbreeding coefficients exceeded 0.1. Population structure assessments using neighbor-joining tree analysis, principal components analysis, and STRUCTURE analysis indicated that no genetic differentiation existed within breeds. LD decay and ROH at different cut-off lengths were used to identify traces left by recent or ancient inbreeding. Few long ROH were identified, indicating that inbreeding has been largely avoided with the current conservation strategy. The observed losses in genetic diversity and occurrences of inbreeding might be consequences of sub-optimal effective population sizes.

CONCLUSIONS: The conserved Chinese chicken populations have high genomic diversity under the current conservation program (R: F). Furthermore, this study highlights the need to monitor dynamic changes in genetic diversity in conserved breeds over successive generations. Our research provides new insights into genetic diversity dynamics in conserved populations, and lays a solid foundation for improving conservation schemes.}, } @article {pmid30092762, year = {2018}, author = {Pietsch, M and Irrgang, A and Roschanski, N and Brenner Michael, G and Hamprecht, A and Rieber, H and Käsbohrer, A and Schwarz, S and Rösler, U and Kreienbrock, L and Pfeifer, Y and Fuchs, S and Werner, G and , }, title = {Whole genome analyses of CMY-2-producing Escherichia coli isolates from humans, animals and food in Germany.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {601}, pmid = {30092762}, issn = {1471-2164}, support = {01KI1313//Bundesministerium für Bildung und Forschung/ ; 01KI1313//Bundesministerium für Bildung und Forschung/ ; 01KI1313//Bundesministerium für Bildung und Forschung/ ; 01KI1313//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Animals ; Cattle ; Chickens ; Escherichia coli/enzymology/*genetics/*isolation & purification/metabolism ; Escherichia coli Infections/microbiology/*veterinary ; Escherichia coli Proteins/genetics/metabolism ; Food Analysis/*methods ; Germany ; Phylogeny ; Polymorphism, Single Nucleotide ; Swine ; Turkeys ; Whole Genome Sequencing/*methods ; beta-Lactamases/genetics/metabolism ; }, abstract = {BACKGROUND: Resistance to 3rd-generation cephalosporins in Escherichia coli is mostly mediated by extended-spectrum beta-lactamases (ESBLs) or AmpC beta-lactamases. Besides overexpression of the species-specific chromosomal ampC gene, acquisition of plasmid-encoded ampC genes, e.g. blaCMY-2, has been described worldwide in E. coli from humans and animals. To investigate a possible transmission of blaCMY-2 along the food production chain, we conducted a next-generation sequencing (NGS)-based analysis of 164 CMY-2-producing E. coli isolates from humans, livestock animals and foodstuff from Germany.

RESULTS: The data of the 164 sequenced isolates revealed 59 different sequence types (STs); the most prevalent ones were ST38 (n = 19), ST131 (n = 16) and ST117 (n = 13). Two STs were present in all reservoirs: ST131 (human n = 8; food n = 2; animal n = 6) and ST38 (human n = 3; animal n = 9; food n = 7). All but one CMY-2-producing ST131 isolates belonged to the clade B (fimH22) that differed substantially from the worldwide dominant CTX-M-15-producing clonal lineage ST131-O25b clade C (fimH30). Plasmid replicon types IncI1 (n = 61) and IncK (n = 72) were identified for the majority of blaCMY-2-carrying plasmids. Plasmid sequence comparisons showed a remarkable sequence identity, especially for IncK plasmids. Associations of replicon types and distinct STs were shown for IncK and ST57, ST429 and ST38 as well as for IncI1 and ST58. Additional β-lactamase genes (blaTEM, blaCTX-M, blaOXA, blaSHV) were detected in 50% of the isolates, and twelve E. coli from chicken and retail chicken meat carried the colistin resistance gene mcr-1.

CONCLUSION: We found isolates of distinct E. coli clonal lineages (ST131 and ST38) in all three reservoirs. However, a direct clonal relationship of isolates from food animals and humans was only noticeable for a few cases. The CMY-2-producing E. coli-ST131 represents a clonal lineage different from the CTX-M-15-producing ST131-O25b cluster. Apart from the ST-driven spread, plasmid-mediated spread, especially via IncI1 and IncK plasmids, likely plays an important role for emergence and transmission of blaCMY-2 between animals and humans.}, } @article {pmid30092759, year = {2018}, author = {Cetina, K and Buenaposada, JM and Baumela, L}, title = {Multi-class segmentation of neuronal structures in electron microscopy images.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {298}, pmid = {30092759}, issn = {1471-2105}, support = {478797//CONACYT/ ; TIN2016-75982-C2-2-R//Ministerio de Economía y Competitividad (ES)/ ; }, abstract = {BACKGROUND: Serial block face scanning electron microscopy (SBFEM) is becoming a popular technology in neuroscience. We have seen in the last years an increasing number of works addressing the problem of segmenting cellular structures in SBFEM images of brain tissue. The vast majority of them is designed to segment one specific structure, typically membranes, synapses and mitochondria. Our hypothesis is that the performance of these algorithms can be improved by concurrently segmenting more than one structure using image descriptions obtained at different scales.

RESULTS: We consider the simultaneous segmentation of two structures, namely, synapses with mitochondria, and mitochondra with membranes. To this end we select three image stacks encompassing different SBFEM acquisition technologies and image resolutions. We introduce both a new Boosting algorithm to perform feature scale selection and the Jaccard Curve as a tool compare several segmentation results. We then experimentally study the gains in performance obtained when simultaneously segmenting two structures with properly selected image descriptor scales. The results show that by doing so we achieve significant gains in segmentation accuracy when compared to the best results in the literature.

CONCLUSIONS: Simultaneously segmenting several neuronal structures described at different scales provides voxel classification algorithms with highly discriminating features that significantly improve segmentation accuracy.}, } @article {pmid30092758, year = {2018}, author = {Schelkunov, MI and Penin, AA and Logacheva, MD}, title = {RNA-seq highlights parallel and contrasting patterns in the evolution of the nuclear genome of fully mycoheterotrophic plants.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {602}, pmid = {30092758}, issn = {1471-2164}, support = {14-50-00150//Russian Science Foundation/ ; 17-14-01315//Russian Science Foundation/ ; }, mesh = {Cell Nucleus/genetics ; *Evolution, Molecular ; Gene Expression Profiling ; *Genome, Plant ; High-Throughput Nucleotide Sequencing/*methods ; Mycorrhizae/*classification/*genetics ; Nuclear Proteins/*genetics ; Phylogeny ; Plant Proteins/genetics ; RNA, Plant/genetics ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: While photosynthesis is the most notable trait of plants, several lineages of plants (so-called full heterotrophs) have adapted to obtain organic compounds from other sources. The switch to heterotrophy leads to profound changes at the morphological, physiological and genomic levels.

RESULTS: Here, we characterize the transcriptomes of three species representing two lineages of mycoheterotrophic plants: orchids (Epipogium aphyllum and Epipogium roseum) and Ericaceae (Hypopitys monotropa). Comparative analysis is used to highlight the parallelism between distantly related fully heterotrophic plants. In both lineages, we observed genome-wide elimination of nuclear genes that encode proteins related to photosynthesis, while systems associated with protein import to plastids as well as plastid transcription and translation remain active. Genes encoding components of plastid ribosomes that have been lost from the plastid genomes have not been transferred to the nuclear genomes; instead, some of the encoded proteins have been substituted by homologs. The nuclear genes of both Epipogium species accumulated nucleotide substitutions twice as rapidly as their photosynthetic relatives; in contrast, no increase in the substitution rate was observed in H. monotropa.

CONCLUSIONS: Full heterotrophy leads to profound changes in nuclear gene content. The observed increase in the rate of nucleotide substitutions is lineage specific, rather than a universal phenomenon among non-photosynthetic plants.}, } @article {pmid30092756, year = {2018}, author = {Myśków, B and Góralska, M and Lenarczyk, N and Czyczyło-Mysza, I and Stojałowski, S}, title = {Putative candidate genes responsible for leaf rolling in rye (Secale cereale L.).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {57}, pmid = {30092756}, issn = {1471-2156}, support = {518070173171-01/18//Ministerstwo Nauki i Szkolnictwa Wyższego/ ; }, abstract = {BACKGROUND: Rolling of leaves (RL) is a phenomenon commonly found in grasses. Morphology of the leaf is an important agronomic trait in field crops especially in rice; therefore, majority of the rice breeders are interested in RL. There are only few studies with respect to RL of wheat and barley; however, the information regarding the genetic base of RL with respect to the shape of leaf in rye is lacking. To the best of our knowledge, this is the first study on the localization of loci controlling RL on high density consensus genetic map of rye.

RESULTS: Genotypic analysis led to the identification of 43 quantitative trait loci (QTLs) for RL, grouped into 28 intervals, which confirms the multigenic base of the trait stated for wheat and rice. Four stable QTLs were located on chromosomes 3R, 5R, and 7R. Co-localization of QTL for RL and for different morphological, biochemical and physiological traits may suggests pleiotropic effects of some QTLs. QTLs for RL were associated with QTLs for such morphological traits as: grain number and weight, spike number per plant, compactness of spike, and plant height. Two QTLs for RL were found to coincide with QTLs for drought tolerance (4R, 7R), two with QTLs for heading earliness (2R, 7R), one with α-amylase activity QTL (7R) and three for pre-harvest sprouting QTL (1R, 4R, 7R). The set of molecular markers strongly linked to RL was selected, and the putative candidate genes controlling the process of RL were identified. Twelve QTLs are considered as linked to candidate genes on the base of DArT sequences alignment, which is a new information for rye.

CONCLUSIONS: Our results expand the knowledge about the network of QTLs for different morphological, biochemical and physiological traits and can be a starting point to studies on particular genes controlling RL and other important agronomic traits (yield, earliness, pre-harvest sprouting, reaction to water deficit) and to appoint markers useful in marker assisted selection (MAS). A better knowledge of the rye genome and genes could both facilitate rye improvement itself and increase the efficiency of utilizing rye genes in wheat breeding.}, } @article {pmid30092755, year = {2018}, author = {Cheng, YH and Liaw, JJ and Kuo, CN}, title = {REHUNT: a reliable and open source package for restriction enzyme hunting.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {178}, pmid = {30092755}, issn = {1471-2105}, abstract = {BACKGROUND: Restriction enzymes are used frequently in biotechnology. However, manual mining of restriction enzymes is challenging. Furthermore, integrating available restriction enzymes into different bioinformatics systems is necessary for many biotechnological applications, such as polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Thus, in the present study, we developed the package REHUNT (Restriction Enzymes HUNTing), which mines restriction enzymes from the public database REBASE using a series of search operations.

RESULTS: REHUNT is a reliable and open source package implemented in JAVA. It provides useful methods and manipulations for biological sequence analysis centered around restriction enzymes contained in REBASE. All available restriction enzymes for the imported biological sequences can be identified by REHUNT. Different genotypes can be identified using PCR-RFLP based on REHUNT for single nucleotide polymorphism (SNP), mutations, and the other variations. REHUNT robustly recognizes multiple inputs with different formats, e.g. regular DNA sequences, variation-in-sequence indicated by IUPAC code, as well as variation-in-sequence indicated by dNTPs format. Variations including di-, tri-, and tetra-allelic types and indel formats are also acceptable. Furthermore, REHUNT provides classified restriction enzymes output, including IUPAC and general sequence types, as well as commercial and non-commercial availabilities. REHUNT also enables analysis for high throughput screening (HTS) technologies.

CONCLUSIONS: REHUNT is open source software with GPL v3 license and can be run on all platforms. Its features include: 1) Quick restriction enzymes search throughout a sequence based on the Boyer-Moore algorithm; 2) all available restriction enzymes provided and regularly updated from REBASE; 3) an open source API available of integrating all types of bioinformatics systems and applications; 4) SNP genotyping available for plant and animal marker-assisted breeding, and for human genetics; and 5) high throughput analysis available for Next Generation Sequencing (NGS). REHUNT not only to effectively looks for restriction enzymes in a sequence, but also available for SNP genotyping. Furthermore, it can be integrated into other biological and medical applications. REHUNT offers a convenient and flexible package for powerful restriction enzymes analyses in association studies, and supports high throughput analysis. The source codes and complete API documents are available at SourceForge: https://sourceforge.net/projects/rehunt/ , GitHub: https://github.com/yuhuei/rehunt , and at: https://sites.google.com/site/yhcheng1981/rehunt .}, } @article {pmid30092357, year = {2018}, author = {Trujillo-Arias, N and Calderón, L and Santos, FR and Miyaki, CY and Aleixo, A and Witt, CC and Tubaro, PL and Cabanne, GS}, title = {Forest corridors between the central Andes and the southern Atlantic Forest enabled dispersal and peripatric diversification without niche divergence in a passerine.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {221-232}, doi = {10.1016/j.ympev.2018.08.005}, pmid = {30092357}, issn = {1095-9513}, abstract = {The central Andean rainforests and the Atlantic Forest are separated by the Chaco and the Cerrado domains. Despite this isolation, diverse evidence suggests that these rainforests have been connected in the past. However, little is known about the timing and geographic positions of these connections, as well as their effects on diversification of species. In this study, we used the Black-goggled Tanager (Trichothraupis melanops, Thraupidae) as a model to study whether the Andean and the Atlantic forests have acted as a refugia system, and to evaluate biogeographic hypotheses of diversification and connection between these rainforests. We compared alternative biogeographic scenarios by using Approximate Bayesian Computation (ABC), modeled range shifts across time, and assessed niche divergence between regions. The results indicated that the major phylogeographic gap within T. melanops is located between these rainforests. The ABC analysis supported peripatric diversification, with initial dispersal from the Atlantic Forest to the Andes during the Mid-Pleistocene. Also, the results supported an Andean-Atlantic forests connection through the current Cerrado-Chaco transition, linking the southern Atlantic Forest with the central Andes. Our findings, taken together with other studies, support that the connection between these biomes has been recurrent, and that has occurred mostly through the Cerrado and/or the Cerrado-Chaco transition. The data also support that the connection dynamic has played an important role in the biological diversification, by promoting peripatric divergence in some forest taxa restricted to both biomes.}, } @article {pmid30092356, year = {2018}, author = {Jiang, W and Zhu, J and Wu, Y and Li, L and Li, Y and Ge, C and Wang, Y and Endersby, NM and Hoffmann, AA and Yu, W}, title = {Influence of Wolbachia infection on mitochondrial DNA variation in the genus Polytremis (Lepidoptera: Hesperiidae).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {158-170}, doi = {10.1016/j.ympev.2018.08.001}, pmid = {30092356}, issn = {1095-9513}, abstract = {The maternally inherited obligate bacteria Wolbachia is known for infecting the reproductive tissues of a wide range of arthropods and can contribute to phylogenetically discordant patterns between mtDNA and nDNA. In this study, we tested for an association between mito-nuclear discordance in Polytremis and Wolbachia infection. Six of the 17 species of Polytremis were found to be infected with Wolbachia. Overall, 34% (70/204) of Polytremis specimens were Wolbachia positive and three strains of Wolbachia identified using a wsp marker were further characterized as six strains based on MLST markers. Wolbachia acquisition in Polytremis appears to occur mainly through horizontal transmission rather than codivergence based on comparison of the divergence times of Wolbachia and Polytremis species. At the intraspecific level, one of the Wolbachia infections (wNas1) is associated with reduced mtDNA polymorphism in the infected Polytremis population. At the interspecific level, there is one case of mito-nuclear discordance likely caused by introgression of P. fukia mtDNA into P. nascens driven by another Wolbachia strain (wNas3). Based on an absence of infected males, we suspect that one Wolbachia strain (wNas2) affects sex ratio, but the phenotypic effects of the other strains are unclear. These data reveal a dynamic interaction between Polytremis and Wolbachia endosymbionts affecting patterns of mtDNA variation.}, } @article {pmid30091699, year = {2018}, author = {Yu, WN and Han, JR and Liu, Y and Du, ZJ and Mu, DS}, title = {Agaribacter flavus sp. nov., isolated from red algae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {10}, pages = {3140-3143}, doi = {10.1099/ijsem.0.002953}, pmid = {30091699}, issn = {1466-5034}, mesh = {Alteromonadaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gracilaria/*microbiology ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, non-motile, aerobic, curved-rod bacterium, designated as strain 2p52T, was isolated from the marine algae Gracilaria blodgettii collected off the coast of Lingshui county, in Hainan province, China. Strain 2p52T grew at 15-42 °C (optimally at 30-33 °C), at pH 6.0-10.0 (7.5-8.0) and in the presence of 1.0-8.0 % (w/v) NaCl (2.0-3.0 %). The most closely related species was Agaribacter marinus (96.5 % 16S rRNA gene sequence similarity). Phylogenetic analysis based on the sequence of the 16S rRNA gene revealed that strain 2p52T belonged to the genus Agaribacter. The novel strain contained phophatidylethanolamine and phosphatidylglycerol as the major polar lipids. The predominant isoprenoid quinine was Q-8, and the DNA G+C content was 43.2 mol%. The major cellular fatty acids were C16 : 1ω7c and/or iso-C15 : 0 2-OH, C16 : 0, and C18 : 1ω7c. The phenotypic and systematic comparative analyses indicated that the isolate is representative of a novel species of the genus Agaribacter, and the name Agaribacter flavus sp. nov. is proposed. The type strain is 2p52T (=KCTC 52473T=MCCC 1H00151T).}, } @article {pmid30091696, year = {2018}, author = {Cao, C and Xu, T and Liu, J and Cai, X and Sun, Y and Qin, S and Jiang, J and Huang, Y}, title = {Actinomadura deserti sp. nov., isolated from desert soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2930-2935}, doi = {10.1099/ijsem.0.002922}, pmid = {30091696}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; *Desert Climate ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-positive, strictly aerobic actinobacterium, designated BMP B8004T, was isolated from desert soil collected in Xinjiang Province, Northwest China. It produced an extensively branched non-fragmenting substrate mycelium, and very scanty aerial mycelium that formed a short hooked chain of arthrospores with a smooth surface. Optimum growth occurred at 28 °C, pH 7.0 and 0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain BMP B8004T formed a distinct phyletic lineage within the genus Actinomadura. It shared the highest 16S rRNA gene sequence similarity to Actinomadura apis IM17-1T (99.2 %) and Actinomadura rifamycini NBRC 14183T (98.6 %). However, it could be distinguished from the two closest strains based on the low levels of DNA-DNA relatedness (52.7±0.7 and 45±1.8 %, respectively). Chemotaxonomic characteristics, including the main phospholipids, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides, the major menaquinones MK-9(H6) and MK-9(H8), the predominant fatty acids iso-C16 : 0, C16 : 0, C18 : 0 10-methyl and C18 : 1ω9c, were also consistent with the properties of the genus Actinomadura. The DNA G+C content of strain BMP B8004T was 71.9 mol%. Based on phenotypic and genotypic features, strain BMP B8004T is considered to represent a novel species of the genus Actinomadura, for which the name Actinomadura deserti sp. nov. is proposed. The type strain is BMP B8004T (=CGMCC 4.7432T=KCTC 39998T).}, } @article {pmid30091694, year = {2018}, author = {Wang, NN and Sang, J and Wang, XQ and Li, YX and Du, ZJ}, title = {Primorskyibacter marinus sp. nov., isolated from coastal sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3169-3174}, doi = {10.1099/ijsem.0.002959}, pmid = {30091694}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative, whitish-yellow, rod-shaped, non-pigmented, aerobic, oxidase-positive and catalase-positive bacterium, designated PX7T, was isolated from coastal sediment of Xiaoshi Island, Weihai, China (37° 31' 36″ N, 122° 00' 58″ E). Strain PX7T grew optimally at 30 °C, at pH 7.0-7.5 and in the presence of 3.0 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain PX7T formed a robust clade with members of the genus Primorskyibacter and was closely related to Primorskyibacter sedentarius, Primorskyibacter aestuariivivens and Primorskyibacter insulae with 96.5, 96.2 and 95.1 % sequence similarities, respectively. The sole respiratory quinone of strain PX7T was ubiquinone-10, and the dominant fatty acid was C18 : 1ω7c (80.2 %). The major polar lipids were phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, one unidentified aminolipid, one unidentified phospholipid and one unidentified lipid. The DNA G+C content of strain PX7T was 60.2 mol%. Based on the combination of phylogenetic analyses, phenotypic and chemotaxonomic data, strain PX7T is considered to represent a novel species within the genus Primorskyibacter in the family Rhodobacteraceae, for which the name Primorskyibacter marinus sp. nov. is proposed. The type strain of the new species is PX7T (=KCTC 42952T=MCCC 1H00196T).}, } @article {pmid30091010, year = {2018}, author = {Bassez, MP}, title = {Water near its Supercritical Point and at Alkaline pH for the Production of Ferric Oxides and Silicates in Anoxic Conditions. A New Hypothesis for the Synthesis of Minerals Observed in Banded Iron Formations and for the Related Geobiotropic Chemistry inside Fluid Inclusions.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {3}, pages = {289-320}, pmid = {30091010}, issn = {1573-0875}, mesh = {Alkalies/chemistry ; Anaerobiosis ; *Earth (Planet) ; Ferric Compounds/chemical synthesis/chemistry ; Hydrogen-Ion Concentration ; Minerals/*chemical synthesis/chemistry ; *Origin of Life ; Oxygen/chemistry/metabolism ; Silicates/chemical synthesis/chemistry ; Solubility ; Temperature ; Ultraviolet Rays ; Water/*chemistry ; }, abstract = {An alternative hypothesis for the origin of the banded iron formations and the synthesis of prebiotic molecules is presented here. I show the importance of considering water near its supercritical point and at alkaline pH. It is based on the chemical equation for the anoxic oxidation of ferrous iron into ferric iron at high-subcritical conditions of water and high pH, that I extract from E-pH diagrams drawn for corrosion purposes (Geophysical Research Abstracts Vol 15, EGU2013-22 Bassez 2013, Orig Life Evol Biosph 45(1):5-13, Bassez 2015, Procedia Earth Planet Sci 17, 492-495, Bassez 2017a, Orig Life Evol Biosph 47:453-480, Bassez 2017b). The sudden change in solubility of silica, SiO2, at the critical point of water is also considered. It is shown that under these temperatures and pressures, ferric oxides and ferric silicates can form in anoxic terrains. No FeII oxidation by UV light, neither by oxygen is needed to explain the minerals of the Banded Iron Formations. The intervention of any kind of microorganisms, either sulfate-reducing, or FeII-oxidizing or O2-producing, is not required. The chemical equation for the anoxic oxidation of ferrous iron is applied to the hydrolyses of fayalite, Fe2SiO4 and ferrosilite, FeSiO3. It is shown that the BIF minerals of the Hamersley Group, Western Australia, and the Transvaal Supergroup, South Africa, are those of fayalite and ferrosilite hydrolyses and carbonations. The dissolution of crustal fayalite and ferrosilite during water-rock interaction needs to occur at T&P just below the critical point of water and in a rising water which is undersaturated in SiO2. Minerals of BIFs which can then be ejected at the surface from venting arcs are ferric oxide hydroxides, hematite, FeIII-greenalite, siderite. The greenalite dehydrated product minnesotaite forms when rising water becomes supersaturated in SiO2, as also riebeckite and stilpnomelane. Long lengths of siderite without ferric oxides neither ferric silicates can occur since the exothermic siderite formation is not so much dependent in T&P. It is also shown that the H2 which is released during hydrolysis/oxidation of fayalite/ferrosilite can lead to components of life, such as macromolecules of amino acids which are synthesized from mixtures of (CO, N2, H2O) in Sabatier-Senderens/Fischer-Tropsch & Haber-Bosch reactions or microwave or gamma-ray excitation reactions. I propose that such geobiotropic synthesis may occur inside fluid inclusions of BIFs, in the silica chert, hematite, FeIII-greenalite or siderite. Therefore, the combination of high-subcritical conditions of water, high solubility of SiO2 at these T&P values, formation of CO also at these T&P, high pH and anoxic water, leads to the formation of ferric minerals and prebiotic molecules in the process of geobiotropy.}, } @article {pmid30090631, year = {2018}, author = {Alvergne, A and Vlajic Wheeler, M and Högqvist Tabor, V}, title = {Do sexually transmitted infections exacerbate negative premenstrual symptoms? Insights from digital health.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {138-150}, pmid = {30090631}, issn = {2050-6201}, abstract = {Background and objectives: The underlying reasons why some women experience debilitating premenstrual symptoms and others do not are largely unknown. Here, we test the evolutionary ecological hypothesis that some negative premenstrual symptoms may be exacerbated by the presence of chronic sexually transmitted infections (STIs).

Methodology: 34 511 women were recruited through a digital period-tracker app. Participants were asked: (i) Have you ever been diagnosed with a STI? (ii) If yes, when was it, and were you given treatment? Those data were combined with longitudinal cycle data on menstrual bleeding patterns, the experience of pain and emotions and hormonal contraceptive use.

Results: 865 women had at least two complete menstrual cycle data and were eligible for analysis. Before diagnosis, the presence of an infection predicts a ca. 2-fold increase in the odds of reporting both headache, cramps and sadness during the late luteal phase and sensitive emotions during the wider luteal phase. After diagnosis, the odds of reporting negative symptoms pre-menstrually remain unchanged among STI negative individuals, but the odds of reporting sensitive emotions decrease among STI positive individuals receiving a treatment. No relationships between STIs, pain and emotions are observed among hormonal contraceptive users.

Conclusions and implications: The results support the idea that a negative premenstrual experience might be aggravated by the presence of undiagnosed STIs, a leading cause of infertility worldwide. Caution is warranted in extrapolating the results as the data are self-reported, inflammatory levels are unknown and the tracker is biased towards recording negative premenstrual symptoms among Western individuals.}, } @article {pmid30089929, year = {2018}, author = {}, title = {Human-embryo editing, genetic privacy and Ebola returns.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {146-147}, doi = {10.1038/d41586-018-05888-2}, pmid = {30089929}, issn = {1476-4687}, mesh = {Ebolavirus/genetics ; Gene Editing ; *Genetic Privacy ; *Hemorrhagic Fever, Ebola ; Humans ; Mutation ; Privacy ; Viral Proteins/genetics ; }, } @article {pmid30089928, year = {2018}, author = {Gibney, E}, title = {Thousands of exotic 'topological' materials discovered through sweeping search.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {151-152}, doi = {10.1038/d41586-018-05913-4}, pmid = {30089928}, issn = {1476-4687}, } @article {pmid30089927, year = {2018}, author = {Butler, D}, title = {The ghost of influenza past and the hunt for a universal vaccine.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {158-160}, doi = {10.1038/d41586-018-05889-1}, pmid = {30089927}, issn = {1476-4687}, mesh = {Child ; *Hemagglutinins ; Humans ; Influenza A Virus, H5N1 Subtype ; Influenza A Virus, H7N9 Subtype ; Influenza Vaccines ; *Influenza, Human ; }, } @article {pmid30089925, year = {2018}, author = {Bollen, J}, title = {Who would you share your funding with?.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {143}, doi = {10.1038/d41586-018-05887-3}, pmid = {30089925}, issn = {1476-4687}, } @article {pmid30089924, year = {2018}, author = {Egli, D and Zuccaro, MV and Kosicki, M and Church, GM and Bradley, A and Jasin, M}, title = {Inter-homologue repair in fertilized human eggs?.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {E5-E7}, doi = {10.1038/s41586-018-0379-5}, pmid = {30089924}, issn = {1476-4687}, } @article {pmid30089923, year = {2018}, author = {Ma, H and Marti-Gutierrez, N and Park, SW and Wu, J and Hayama, T and Darby, H and Van Dyken, C and Li, Y and Koski, A and Liang, D and Suzuki, K and Gu, Y and Gong, J and Xu, X and Ahmed, R and Lee, Y and Kang, E and Ji, D and Park, AR and Kim, D and Kim, ST and Heitner, SB and Battaglia, D and Krieg, SA and Lee, DM and Wu, DH and Wolf, DP and Amato, P and Kaul, S and Belmonte, JCI and Kim, JS and Mitalipov, S}, title = {Ma et al. reply.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {E10-E23}, doi = {10.1038/s41586-018-0381-y}, pmid = {30089923}, issn = {1476-4687}, } @article {pmid30089922, year = {2018}, author = {Adikusuma, F and Piltz, S and Corbett, MA and Turvey, M and McColl, SR and Helbig, KJ and Beard, MR and Hughes, J and Pomerantz, RT and Thomas, PQ}, title = {Large deletions induced by Cas9 cleavage.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {E8-E9}, doi = {10.1038/s41586-018-0380-z}, pmid = {30089922}, issn = {1476-4687}, } @article {pmid30089921, year = {2018}, author = {Rein, M and Favrod, VD and Hou, C and Khudiyev, T and Stolyarov, A and Cox, J and Chung, CC and Chhav, C and Ellis, M and Joannopoulos, J and Fink, Y}, title = {Diode fibres for fabric-based optical communications.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {214-218}, doi = {10.1038/s41586-018-0390-x}, pmid = {30089921}, issn = {1476-4687}, abstract = {Semiconductor diodes are basic building blocks of modern computation, communications and sensing1. As such, incorporating them into textile-grade fibres can increase fabric capabilities and functions2, to encompass, for example, fabric-based communications or physiological monitoring. However, processing challenges have so far precluded the realization of semiconducting diodes of high quality in thermally drawn fibres. Here we demonstrate a scalable thermal drawing process of electrically connected diode fibres. We begin by constructing a macroscopic preform that hosts discrete diodes internal to the structure alongside hollow channels through which conducting copper or tungsten wires are fed. As the preform is heated and drawn into a fibre, the conducting wires approach the diodes until they make electrical contact, resulting in hundreds of diodes connected in parallel inside a single fibre. Two types of in-fibre device are realized: light-emitting and photodetecting p-i-n diodes. An inter-device spacing smaller than 20 centimetres is achieved, as well as light collimation and focusing by a lens designed in the fibre cladding. Diode fibres maintain performance throughout ten machine-wash cycles, indicating the relevance of this approach to apparel applications. To demonstrate the utility of this approach, a three-megahertz bi-directional optical communication link is established between two fabrics containing receiver-emitter fibres. Finally, heart-rate measurements with the diodes indicate their potential for implementation in all-fabric physiological-status monitoring systems. Our approach provides a path to realizing ever more sophisticated functions in fibres, presenting the prospect of a fibre 'Moore's law' analogue through the increase of device density and function in thermally drawn textile-ready fibres.}, } @article {pmid30089920, year = {2018}, author = {Parai, R and Mukhopadhyay, S}, title = {Xenon isotopic constraints on the history of volatile recycling into the mantle.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {223-227}, doi = {10.1038/s41586-018-0388-4}, pmid = {30089920}, issn = {1476-4687}, abstract = {The long-term exchange of volatile species (such as water, carbon, nitrogen and the noble gases) between deep Earth and surface reservoirs controls the habitability of the Earth's surface. The present-day volatile budget of the mantle reflects the integrated history of outgassing and retention of primordial volatiles delivered to the planet during accretion, volatile species generated by radiogenic ingrowth and volatiles transported into the mantle from surface reservoirs over time. Variations in the distribution of volatiles between deep Earth and surface reservoirs affect the viscosity, cooling rate and convective stress state of the solid Earth. Accordingly, constraints on the flux of surface volatiles transported into the deep Earth improve our understanding of mantle convection and plate tectonics. However, the history of surface volatile regassing into the mantle is not known. Here we use mantle xenon isotope systematics to constrain the age of initiation of volatile regassing into the deep Earth. Given evidence of prolonged evolution of the xenon isotopic composition of the atmosphere1,2, we find that substantial recycling of atmospheric xenon into the deep Earth could not have occurred before 2.5 billion years ago. Xenon concentrations in downwellings remained low relative to ambient convecting mantle concentrations throughout the Archaean era, and the mantle shifted from a net degassing to a net regassing regime after 2.5 billion years ago. Because xenon is carried into the Earth's interior in hydrous mineral phases3-5, our results indicate that downwellings were drier in the Archaean era relative to the present. Progressive drying of the Archean mantle would allow slower convection and decreased heat transport out of the mantle, suggesting non-monotonic thermal evolution of the Earth's interior.}, } @article {pmid30089919, year = {2018}, author = {Gröning, O and Wang, S and Yao, X and Pignedoli, CA and Borin Barin, G and Daniels, C and Cupo, A and Meunier, V and Feng, X and Narita, A and Müllen, K and Ruffieux, P and Fasel, R}, title = {Engineering of robust topological quantum phases in graphene nanoribbons.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {209-213}, doi = {10.1038/s41586-018-0375-9}, pmid = {30089919}, issn = {1476-4687}, abstract = {Boundaries between distinct topological phases of matter support robust, yet exotic quantum states such as spin-momentum locked transport channels or Majorana fermions1-3. The idea of using such states in spintronic devices or as qubits in quantum information technology is a strong driver of current research in condensed matter physics4-6. The topological properties of quantum states have helped to explain the conductivity of doped trans-polyacetylene in terms of dispersionless soliton states7-9. In their seminal paper, Su, Schrieffer and Heeger (SSH) described these exotic quantum states using a one-dimensional tight-binding model10,11. Because the SSH model describes chiral topological insulators, charge fractionalization and spin-charge separation in one dimension, numerous efforts have been made to realize the SSH Hamiltonian in cold-atom, photonic and acoustic experimental configurations12-14. It is, however, desirable to rationally engineer topological electronic phases into stable and processable materials to exploit the corresponding quantum states. Here we present a flexible strategy based on atomically precise graphene nanoribbons to design robust nanomaterials exhibiting the valence electronic structures described by the SSH Hamiltonian15-17. We demonstrate the controlled periodic coupling of topological boundary states18 at junctions of graphene nanoribbons with armchair edges to create quasi-one-dimensional trivial and non-trivial electronic quantum phases. This strategy has the potential to tune the bandwidth of the topological electronic bands close to the energy scale of proximity-induced spin-orbit coupling19 or superconductivity20, and may allow the realization of Kitaev-like Hamiltonians3 and Majorana-type end states21.}, } @article {pmid30089918, year = {2018}, author = {Rizzo, DJ and Veber, G and Cao, T and Bronner, C and Chen, T and Zhao, F and Rodriguez, H and Louie, SG and Crommie, MF and Fischer, FR}, title = {Topological band engineering of graphene nanoribbons.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {204-208}, doi = {10.1038/s41586-018-0376-8}, pmid = {30089918}, issn = {1476-4687}, abstract = {Topological insulators are an emerging class of materials that host highly robust in-gap surface or interface states while maintaining an insulating bulk1,2. Most advances in this field have focused on topological insulators and related topological crystalline insulators3 in two dimensions4-6 and three dimensions7-10, but more recent theoretical work has predicted the existence of one-dimensional symmetry-protected topological phases in graphene nanoribbons (GNRs)11. The topological phase of these laterally confined, semiconducting strips of graphene is determined by their width, edge shape and terminating crystallographic unit cell and is characterized by a [Formula: see text] invariant12 (that is, an index of either 0 or 1, indicating two topological classes-similar to quasi-one-dimensional solitonic systems13-16). Interfaces between topologically distinct GNRs characterized by different values of [Formula: see text] are predicted to support half-filled, in-gap localized electronic states that could, in principle, be used as a tool for material engineering11. Here we present the rational design and experimental realization of a topologically engineered GNR superlattice that hosts a one-dimensional array of such states, thus generating otherwise inaccessible electronic structures. This strategy also enables new end states to be engineered directly into the termini of the one-dimensional GNR superlattice. Atomically precise topological GNR superlattices were synthesized from molecular precursors on a gold surface, Au(111), under ultrahigh-vacuum conditions and characterized by low-temperature scanning tunnelling microscopy and spectroscopy. Our experimental results and first-principles calculations reveal that the frontier band structure (the bands bracketing filled and empty states) of these GNR superlattices is defined purely by the coupling between adjacent topological interface states. This manifestation of non-trivial one-dimensional topological phases presents a route to band engineering in one-dimensional materials based on precise control of their electronic topology, and is a promising platform for studies of one-dimensional quantum spin physics.}, } @article {pmid30089917, year = {2018}, author = {Kummer, E and Leibundgut, M and Rackham, O and Lee, RG and Boehringer, D and Filipovska, A and Ban, N}, title = {Unique features of mammalian mitochondrial translation initiation revealed by cryo-EM.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {263-267}, doi = {10.1038/s41586-018-0373-y}, pmid = {30089917}, issn = {1476-4687}, abstract = {Mitochondria maintain their own specialized protein synthesis machinery, which in mammals is used exclusively for the synthesis of the membrane proteins responsible for oxidative phosphorylation1,2. The initiation of protein synthesis in mitochondria differs substantially from bacterial or cytosolic translation systems. Mitochondrial translation initiation lacks initiation factor 1, which is essential in all other translation systems from bacteria to mammals3,4. Furthermore, only one type of methionyl transfer RNA (tRNAMet) is used for both initiation and elongation4,5, necessitating that the initiation factor specifically recognizes the formylated version of tRNAMet (fMet-tRNAMet). Lastly, most mitochondrial mRNAs do not possess 5' leader sequences to promote mRNA binding to the ribosome2. There is currently little mechanistic insight into mammalian mitochondrial translation initiation, and it is not clear how mRNA engagement, initiator-tRNA recruitment and start-codon selection occur. Here we determine the cryo-EM structure of the complete translation initiation complex from mammalian mitochondria at 3.2 Å. We describe the function of an additional domain insertion that is present in the mammalian mitochondrial initiation factor 2 (mtIF2). By closing the decoding centre, this insertion stabilizes the binding of leaderless mRNAs and induces conformational changes in the rRNA nucleotides involved in decoding. We identify unique features of mtIF2 that are required for specific recognition of fMet-tRNAMet and regulation of its GTPase activity. Finally, we observe that the ribosomal tunnel in the initiating ribosome is blocked by insertion of the N-terminal portion of mitochondrial protein mL45, which becomes exposed as the ribosome switches to elongation mode and may have an additional role in targeting of mitochondrial ribosomes to the protein-conducting pore in the inner mitochondrial membrane.}, } @article {pmid30089911, year = {2018}, author = {Chen, G and Huang, AC and Zhang, W and Zhang, G and Wu, M and Xu, W and Yu, Z and Yang, J and Wang, B and Sun, H and Xia, H and Man, Q and Zhong, W and Antelo, LF and Wu, B and Xiong, X and Liu, X and Guan, L and Li, T and Liu, S and Yang, R and Lu, Y and Dong, L and McGettigan, S and Somasundaram, R and Radhakrishnan, R and Mills, G and Lu, Y and Kim, J and Chen, YH and Dong, H and Zhao, Y and Karakousis, GC and Mitchell, TC and Schuchter, LM and Herlyn, M and Wherry, EJ and Xu, X and Guo, W}, title = {Exosomal PD-L1 contributes to immunosuppression and is associated with anti-PD-1 response.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {382-386}, pmid = {30089911}, issn = {1476-4687}, support = {R01 GM085146/GM/NIGMS NIH HHS/United States ; R01 GM111128/GM/NIGMS NIH HHS/United States ; R01 AI105343/AI/NIAID NIH HHS/United States ; U19 AI082630/AI/NIAID NIH HHS/United States ; U19 AI117950/AI/NIAID NIH HHS/United States ; P01 CA114046/CA/NCI NIH HHS/United States ; P01 CA025874/CA/NCI NIH HHS/United States ; P30 CA010815/CA/NCI NIH HHS/United States ; U54 CA193417/CA/NCI NIH HHS/United States ; R01 CA047159/CA/NCI NIH HHS/United States ; P50 CA174523/CA/NCI NIH HHS/United States ; }, abstract = {Tumour cells evade immune surveillance by upregulating the surface expression of programmed death-ligand 1 (PD-L1), which interacts with programmed death-1 (PD-1) receptor on T cells to elicit the immune checkpoint response1,2. Anti-PD-1 antibodies have shown remarkable promise in treating tumours, including metastatic melanoma2-4. However, the patient response rate is low4,5. A better understanding of PD-L1-mediated immune evasion is needed to predict patient response and improve treatment efficacy. Here we report that metastatic melanomas release extracellular vesicles, mostly in the form of exosomes, that carry PD-L1 on their surface. Stimulation with interferon-γ (IFN-γ) increases the amount of PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumour growth. In patients with metastatic melanoma, the level of circulating exosomal PD-L1 positively correlates with that of IFN-γ, and varies during the course of anti-PD-1 therapy. The magnitudes of the increase in circulating exosomal PD-L1 during early stages of treatment, as an indicator of the adaptive response of the tumour cells to T cell reinvigoration, stratifies clinical responders from non-responders. Our study unveils a mechanism by which tumour cells systemically suppress the immune system, and provides a rationale for the application of exosomal PD-L1 as a predictor for anti-PD-1 therapy.}, } @article {pmid30089910, year = {2018}, author = {Walsh, JJ and Christoffel, DJ and Heifets, BD and Ben-Dor, GA and Selimbeyoglu, A and Hung, LW and Deisseroth, K and Malenka, RC}, title = {5-HT release in nucleus accumbens rescues social deficits in mouse autism model.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {589-594}, doi = {10.1038/s41586-018-0416-4}, pmid = {30089910}, issn = {1476-4687}, support = {F32 MH103949/MH/NIMH NIH HHS/United States ; }, abstract = {Dysfunction in prosocial interactions is a core symptom of autism spectrum disorder. However, the neural mechanisms that underlie sociability are poorly understood, limiting the rational development of therapies to treat social deficits. Here we show in mice that bidirectional modulation of the release of serotonin (5-HT) from dorsal raphe neurons in the nucleus accumbens bidirectionally modifies sociability. In a mouse model of a common genetic cause of autism spectrum disorder-a copy number variation on chromosome 16p11.2-genetic deletion of the syntenic region from 5-HT neurons induces deficits in social behaviour and decreases dorsal raphe 5-HT neuronal activity. These sociability deficits can be rescued by optogenetic activation of dorsal raphe 5-HT neurons, an effect requiring and mimicked by activation of 5-HT1b receptors in the nucleus accumbens. These results demonstrate an unexpected role for 5-HT action in the nucleus accumbens in social behaviours, and suggest that targeting this mechanism may prove therapeutically beneficial.}, } @article {pmid30089909, year = {2018}, author = {Proctor, J and Hsiang, S and Burney, J and Burke, M and Schlenker, W}, title = {Estimating global agricultural effects of geoengineering using volcanic eruptions.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {480-483}, doi = {10.1038/s41586-018-0417-3}, pmid = {30089909}, issn = {1476-4687}, support = {CNH-L 1715557//National Science Foundation/International ; DGE-1752814//National Science Foundation/International ; }, abstract = {Solar radiation management is increasingly considered to be an option for managing global temperatures1,2, yet the economic effects of ameliorating climatic changes by scattering sunlight back to space remain largely unknown3. Although solar radiation management may increase crop yields by reducing heat stress4, the effects of concomitant changes in available sunlight have never been empirically estimated. Here we use the volcanic eruptions that inspired modern solar radiation management proposals as natural experiments to provide the first estimates, to our knowledge, of how the stratospheric sulfate aerosols created by the eruptions of El Chichón and Mount Pinatubo altered the quantity and quality of global sunlight, and how these changes in sunlight affected global crop yields. We find that the sunlight-mediated effect of stratospheric sulfate aerosols on yields is negative for both C4 (maize) and C3 (soy, rice and wheat) crops. Applying our yield model to a solar radiation management scenario based on stratospheric sulfate aerosols, we find that projected mid-twenty-first century damages due to scattering sunlight caused by solar radiation management are roughly equal in magnitude to benefits from cooling. This suggests that solar radiation management-if deployed using stratospheric sulfate aerosols similar to those emitted by the volcanic eruptions it seeks to mimic-would, on net, attenuate little of the global agricultural damage from climate change. Our approach could be extended to study the effects of solar radiation management on other global systems, such as human health or ecosystem function.}, } @article {pmid30089908, year = {2018}, author = {Vještica, A and Merlini, L and Nkosi, PJ and Martin, SG}, title = {Gamete fusion triggers bipartite transcription factor assembly to block re-fertilization.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {397-400}, doi = {10.1038/s41586-018-0407-5}, pmid = {30089908}, issn = {1476-4687}, abstract = {The ploidy cycle, which is integral to sexual reproduction, requires meiosis to halve chromosome numbers as well as mechanisms that ensure zygotes are formed by exactly two partners1-4. During sexual reproduction of the fungal model organism Schizosaccharomyces pombe, haploid P and M cells fuse to form a diploid zygote that immediately enters meiosis5. Here we reveal that rapid post-fusion reconstitution of a bipartite transcription factor blocks re-fertilization. We first identify mutants that undergo transient cell fusion involving cytosol exchange but not karyogamy, and show that this drives distinct cell fates in the two gametes. The P partner undergoes lethal haploid meiosis, whereas the M cell persists in mating. The zygotic transcription that drives meiosis is rapidly initiated first from the P parental genome, even in wild-type cells. This asymmetric gene expression depends on a bipartite complex formed post-fusion between the cytosolic M-cell-specific peptide Mi and the nuclear P-cell-specific homeobox protein Pi6,7, which captures Mi in the P nucleus. Zygotic transcription is thus poised to initiate in the P nucleus as fast as Mi reaches it after fusion, a design that we reconstruct using two synthetic interactors localized to the nucleus and the cytosol of two respective partner cells. Notably, delaying zygotic transcription-by postponing Mi expression or deleting its transcriptional target in the P genome-leads to zygotes fusing with additional gametes, thus forming polyploids and eventually aneuploid progeny. The signalling cascade to block re-fertilization shares components with, but bifurcates from, meiotic induction8-10. Thus, a cytoplasmic connection upon gamete fusion leads to asymmetric reconstitution of a bipartite transcription factor to rapidly block re-fertilization and induce meiosis, ensuring genome maintenance during sexual reproduction.}, } @article {pmid30089907, year = {2018}, author = {Isson, TT and Planavsky, NJ}, title = {Reverse weathering as a long-term stabilizer of marine pH and planetary climate.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {471-475}, doi = {10.1038/s41586-018-0408-4}, pmid = {30089907}, issn = {1476-4687}, support = {NNA15BB03A/NASA/NASA/United States ; }, mesh = {Atmosphere/chemistry ; Carbon Cycle ; Carbon Dioxide/analysis ; *Climate ; Geologic Sediments/*chemistry ; Hydrogen-Ion Concentration ; Methane/metabolism ; Oceans and Seas ; Partial Pressure ; Seawater/*chemistry ; Silicon Dioxide/analysis/chemistry ; }, abstract = {For the first four billion years of Earth's history, climate was marked by apparent stability and warmth despite the Sun having lower luminosity1. Proposed mechanisms for maintaining an elevated partial pressure of carbon dioxide in the atmosphere ([Formula: see text]) centre on a reduction in the weatherability of Earth's crust and therefore in the efficiency of carbon dioxide removal from the atmosphere2. However, the effectiveness of these mechanisms remains debated2,3. Here we use a global carbon cycle model to explore the evolution of processes that govern marine pH, a factor that regulates the partitioning of carbon between the ocean and the atmosphere. We find that elevated rates of 'reverse weathering'-that is, the consumption of alkalinity and generation of acidity during marine authigenic clay formation4-7-enhanced the retention of carbon within the ocean-atmosphere system, leading to an elevated [Formula: see text] baseline. Although this process is dampened by sluggish kinetics today, we propose that more prolific rates of reverse weathering would have persisted under the pervasively silica-rich conditions8,9 that dominated Earth's early oceans. This distinct ocean and coupled carbon-silicon cycle state would have successfully maintained the equable and ice-free environment that characterized most of the Precambrian period. Further, we propose that during this time, the establishment of a strong negative feedback between marine pH and authigenic clay formation would have also enhanced climate stability by mitigating large swings in [Formula: see text]-a critical component of Earth's natural thermostat that would have been dominant for most of Earth's history. We speculate that the late ecological rise of siliceous organisms8 and a resulting decline in silica-rich conditions dampened the reverse weathering buffer, destabilizing Earth's climate system and lowering baseline [Formula: see text].}, } @article {pmid30089906, year = {2018}, author = {La Manno, G and Soldatov, R and Zeisel, A and Braun, E and Hochgerner, H and Petukhov, V and Lidschreiber, K and Kastriti, ME and Lönnerberg, P and Furlan, A and Fan, J and Borm, LE and Liu, Z and van Bruggen, D and Guo, J and He, X and Barker, R and Sundström, E and Castelo-Branco, G and Cramer, P and Adameyko, I and Linnarsson, S and Kharchenko, PV}, title = {RNA velocity of single cells.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {494-498}, pmid = {30089906}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; R01 HL131768/HL/NHLBI NIH HHS/United States ; }, abstract = {RNA abundance is a powerful indicator of the state of individual cells. Single-cell RNA sequencing can reveal RNA abundance with high quantitative accuracy, sensitivity and throughput1. However, this approach captures only a static snapshot at a point in time, posing a challenge for the analysis of time-resolved phenomena such as embryogenesis or tissue regeneration. Here we show that RNA velocity-the time derivative of the gene expression state-can be directly estimated by distinguishing between unspliced and spliced mRNAs in common single-cell RNA sequencing protocols. RNA velocity is a high-dimensional vector that predicts the future state of individual cells on a timescale of hours. We validate its accuracy in the neural crest lineage, demonstrate its use on multiple published datasets and technical platforms, reveal the branching lineage tree of the developing mouse hippocampus, and examine the kinetics of transcription in human embryonic brain. We expect RNA velocity to greatly aid the analysis of developmental lineages and cellular dynamics, particularly in humans.}, } @article {pmid30089905, year = {2018}, author = {Richardson, AD and Hufkens, K and Milliman, T and Aubrecht, DM and Furze, ME and Seyednasrollah, B and Krassovski, MB and Latimer, JM and Nettles, WR and Heiderman, RR and Warren, JM and Hanson, PJ}, title = {Ecosystem warming extends vegetation activity but heightens vulnerability to cold temperatures.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {368-371}, doi = {10.1038/s41586-018-0399-1}, pmid = {30089905}, issn = {1476-4687}, support = {DE-AC05-00OR22725//US Department of Energy/International ; EF-1065029//Department of Energy/International ; EF-1702697//Department of Energy/International ; }, abstract = {Shifts in vegetation phenology are a key example of the biological effects of climate change1-3. However, there is substantial uncertainty about whether these temperature-driven trends will continue, or whether other factors-for example, photoperiod-will become more important as warming exceeds the bounds of historical variability4,5. Here we use phenological transition dates derived from digital repeat photography6 to show that experimental whole-ecosystem warming treatments7 of up to +9 °C linearly correlate with a delayed autumn green-down and advanced spring green-up of the dominant woody species in a boreal Picea-Sphagnum bog. Results were confirmed by direct observation of both vegetative and reproductive phenology of these and other bog plant species, and by multiple years of observations. There was little evidence that the observed responses were constrained by photoperiod. Our results indicate a likely extension of the period of vegetation activity by 1-2 weeks under a 'CO2 stabilization' climate scenario (+2.6 ± 0.7 °C), and 3-6 weeks under a 'high-CO2 emission' scenario (+5.9 ± 1.1 °C), by the end of the twenty-first century. We also observed severe tissue mortality in the warmest enclosures after a severe spring frost event. Failure to cue to photoperiod resulted in precocious green-up and a premature loss of frost hardiness8, which suggests that vulnerability to spring frost damage will increase in a warmer world9,10. Vegetation strategies that have evolved to balance tradeoffs associated with phenological temperature tracking may be optimal under historical climates, but these strategies may not be optimized for future climate regimes. These in situ experimental results are of particular importance because boreal forests have both a circumpolar distribution and a key role in the global carbon cycle11.}, } @article {pmid30089904, year = {2018}, author = {Ben-David, U and Siranosian, B and Ha, G and Tang, H and Oren, Y and Hinohara, K and Strathdee, CA and Dempster, J and Lyons, NJ and Burns, R and Nag, A and Kugener, G and Cimini, B and Tsvetkov, P and Maruvka, YE and O'Rourke, R and Garrity, A and Tubelli, AA and Bandopadhayay, P and Tsherniak, A and Vazquez, F and Wong, B and Birger, C and Ghandi, M and Thorner, AR and Bittker, JA and Meyerson, M and Getz, G and Beroukhim, R and Golub, TR}, title = {Genetic and transcriptional evolution alters cancer cell line drug response.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {325-330}, doi = {10.1038/s41586-018-0409-3}, pmid = {30089904}, issn = {1476-4687}, support = {R01 CA188228/CA/NCI NIH HHS/United States ; }, abstract = {Human cancer cell lines are the workhorse of cancer research. Although cell lines are known to evolve in culture, the extent of the resultant genetic and transcriptional heterogeneity and its functional consequences remain understudied. Here we use genomic analyses of 106 human cell lines grown in two laboratories to show extensive clonal diversity. Further comprehensive genomic characterization of 27 strains of the common breast cancer cell line MCF7 uncovered rapid genetic diversification. Similar results were obtained with multiple strains of 13 additional cell lines. Notably, genetic changes were associated with differential activation of gene expression programs and marked differences in cell morphology and proliferation. Barcoding experiments showed that cell line evolution occurs as a result of positive clonal selection that is highly sensitive to culture conditions. Analyses of single-cell-derived clones demonstrated that continuous instability quickly translates into heterogeneity of the cell line. When the 27 MCF7 strains were tested against 321 anti-cancer compounds, we uncovered considerably different drug responses: at least 75% of compounds that strongly inhibited some strains were completely inactive in others. This study documents the extent, origins and consequences of genetic variation within cell lines, and provides a framework for researchers to measure such variation in efforts to support maximally reproducible cancer research.}, } @article {pmid30089903, year = {2018}, author = {Song, XP and Hansen, MC and Stehman, SV and Potapov, PV and Tyukavina, A and Vermote, EF and Townshend, JR}, title = {Global land change from 1982 to 2016.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {639-643}, doi = {10.1038/s41586-018-0411-9}, pmid = {30089903}, issn = {1476-4687}, abstract = {Land change is a cause and consequence of global environmental change1,2. Changes in land use and land cover considerably alter the Earth's energy balance and biogeochemical cycles, which contributes to climate change and-in turn-affects land surface properties and the provision of ecosystem services1-4. However, quantification of global land change is lacking. Here we analyse 35 years' worth of satellite data and provide a comprehensive record of global land-change dynamics during the period 1982-2016. We show that-contrary to the prevailing view that forest area has declined globally5-tree cover has increased by 2.24 million km2 (+7.1% relative to the 1982 level). This overall net gain is the result of a net loss in the tropics being outweighed by a net gain in the extratropics. Global bare ground cover has decreased by 1.16 million km2 (-3.1%), most notably in agricultural regions in Asia. Of all land changes, 60% are associated with direct human activities and 40% with indirect drivers such as climate change. Land-use change exhibits regional dominance, including tropical deforestation and agricultural expansion, temperate reforestation or afforestation, cropland intensification and urbanization. Consistently across all climate domains, montane systems have gained tree cover and many arid and semi-arid ecosystems have lost vegetation cover. The mapped land changes and the driver attributions reflect a human-dominated Earth system. The dataset we developed may be used to improve the modelling of land-use changes, biogeochemical cycles and vegetation-climate interactions to advance our understanding of global environmental change1-4,6.}, } @article {pmid30089902, year = {2018}, author = {Fulde, M and Sommer, F and Chassaing, B and van Vorst, K and Dupont, A and Hensel, M and Basic, M and Klopfleisch, R and Rosenstiel, P and Bleich, A and Bäckhed, F and Gewirtz, AT and Hornef, MW}, title = {Neonatal selection by Toll-like receptor 5 influences long-term gut microbiota composition.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {489-493}, doi = {10.1038/s41586-018-0395-5}, pmid = {30089902}, issn = {1476-4687}, abstract = {Alterations in enteric microbiota are associated with several highly prevalent immune-mediated and metabolic diseases1-3, and experiments involving faecal transplants have indicated that such alterations have a causal role in at least some such conditions4-6. The postnatal period is particularly critical for the development of microbiota composition, host-microbe interactions and immune homeostasis7-9. However, the underlying molecular mechanisms of this neonatal priming period have not been defined. Here we report the identification of a host-mediated regulatory circuit of bacterial colonization that acts solely during the early neonatal period but influences life-long microbiota composition. We demonstrate age-dependent expression of the flagellin receptor Toll-like receptor 5 (TLR5) in the gut epithelium of neonate mice. Using competitive colonization experiments, we demonstrate that epithelial TLR5-mediated REG3γ production is critical for the counter-selection of colonizing flagellated bacteria. Comparative microbiota transfer experiments in neonate and adult wild-type and Tlr5-deficient germ-free mice reveal that neonatal TLR5 expression strongly influences the composition of the microbiota throughout life. Thus, the beneficial microbiota in the adult host is shaped during early infancy. This might explain why environmental factors that disturb the establishment of the microbiota during early life can affect immune homeostasis and health in adulthood.}, } @article {pmid30089860, year = {2018}, author = {Chen, J and Guccini, I and Di Mitri, D and Brina, D and Revandkar, A and Sarti, M and Pasquini, E and Alajati, A and Pinton, S and Losa, M and Civenni, G and Catapano, CV and Sgrignani, J and Cavalli, A and D'Antuono, R and Asara, JM and Morandi, A and Chiarugi, P and Crotti, S and Agostini, M and Montopoli, M and Masgras, I and Rasola, A and Garcia-Escudero, R and Delaleu, N and Rinaldi, A and Bertoni, F and de Bono, J and Carracedo, A and Alimonti, A}, title = {Publisher Correction: Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1343}, doi = {10.1038/s41588-018-0181-1}, pmid = {30089860}, issn = {1546-1718}, abstract = {In the HTML version of this article initially published, the name of author Diletta Di Mitri was miscoded in the XML such that Di was included as part of the given name instead of the family name. The error has been corrected in the HTML version of the article.}, } @article {pmid30089805, year = {2018}, author = {Tewary, M and Shakiba, N and Zandstra, PW}, title = {Stem cell bioengineering: building from stem cell biology.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {595-614}, doi = {10.1038/s41576-018-0040-z}, pmid = {30089805}, issn = {1471-0064}, abstract = {New fundamental discoveries in stem cell biology have yielded potentially transformative regenerative therapeutics. However, widespread implementation of stem-cell-derived therapeutics remains sporadic. Barriers that impede the development of these therapeutics can be linked to our incomplete understanding of how the regulatory networks that encode stem cell fate govern the development of the complex tissues and organs that are ultimately required for restorative function. Bioengineering tools, strategies and design principles represent core components of the stem cell bioengineering toolbox. Applied to the different layers of complexity present in stem-cell-derived systems - from gene regulatory networks in single stem cells to the systemic interactions of stem-cell-derived organs and tissues - stem cell bioengineering can address existing challenges and advance regenerative medicine and cellular therapies.}, } @article {pmid30089791, year = {2018}, author = {Berné, O}, title = {Are women the losers in team cosmology prize?.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {307}, doi = {10.1038/d41586-018-05906-3}, pmid = {30089791}, issn = {1476-4687}, } @article {pmid30089520, year = {2018}, author = {Luo, D and Lai, M and Xu, C and Shi, H and Liu, X}, title = {Life history traits in a capital breeding pine caterpillar: effect of host species and needle age.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {24}, pmid = {30089520}, issn = {1472-6785}, support = {31360092//National Natural Science Foundation of China/International ; }, abstract = {BACKGROUND: For capital breeding Lepidoptera, larval food quality is a key determinant of their fitness. A series of studies have suggested that the larval host species or varieties dramatically impact their development and reproductive output. However, few studies have reported the role of foliar age and adult mating success has often been ignored in these studies. In this paper, the influence of host species and needle age on larval performances, adult mating behavior and fitness consequences has been studied using a capital breeding caterpillar, Dendrolimus punctatus Walker (Lepidoptera:Lasiocampidae).

RESULTS: In larval performance trial, a strong effect of larval host species and needle age was found on survivorship, developmental duration, body weight, percentage of adult emergence, and growth index, but not on percentage of female progeny. In adult mating trial, larval host species and needle age also significantly affected mating latency and mating duration, but not mating success. In adult fitness trial, female fecundity, longevity and fitness index, but not oviposition duration and fertility, influenced by larval host species and needle age.

CONCLUSIONS: These results reveal the importance of larval host species and needle age on larval performance and adult reproductive fitness in this capital breeding insect and provide strong evidence that old needles of masson pine P. massoniana is the best host for D. punctatus.}, } @article {pmid30089518, year = {2018}, author = {Singh, A and Lasek-Nesselquist, E and Chaturvedi, V and Chaturvedi, S}, title = {Trichoderma polysporum selectively inhibits white-nose syndrome fungal pathogen Pseudogymnoascus destructans amidst soil microbes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {139}, pmid = {30089518}, issn = {2049-2618}, mesh = {Animals ; Chiroptera/*microbiology ; Colony Count, Microbial ; Disease Resistance ; Fungi/classification/isolation & purification ; Metagenomics/*methods ; Mycoses/prevention & control/veterinary ; Saccharomycetales/*growth & development/pathogenicity ; Sequence Analysis, DNA ; Soil Microbiology ; Trichoderma/*physiology ; }, abstract = {BACKGROUND: Pseudogymnoascus destructans (Pd), the causative fungal agent of white-nose syndrome (WNS), has led to the deaths of millions of hibernating bats in the United States of America (USA) and Canada. Efficient strategies are needed to decontaminate Pd from the bat hibernacula to interrupt the disease transmission cycle without affecting the native microbes. Previously, we discovered a novel Trichoderma polysporum (Tp) strain (WPM 39143), which inhibited the growth of Pd in autoclaved soil samples. In the present investigation, we used culture-based approaches to determine Tp-induced killing of native and enriched Pd in the natural soil of two bat hibernacula. We also assessed the impact of Tp treatment on native microbial communities by metagenomics.

RESULTS: Our results demonstrated that Tp at the concentration of 105 conidia/g soil caused 100% killing of native Pd in culture within 5 weeks of incubation. A 10-fold higher concentration of Tp (106 conidia/g soil) killed an enriched Pd population (105 conidia/g soil). The 12,507 fungal operational taxonomic units (OTUs, dominated by Ascomycota and Basidiomycota) and 27,427 bacterial OTUs (dominated by Acidobacteria and Proteobacteria) comprised the native soil microbes of the two bat hibernacula. No significant differences in fungal and bacterial relative abundances were observed between untreated and Tp-treated soil (105 Tp conidia/g soil, p ≤ 0.05).

CONCLUSIONS: Our results suggest that Tp-induced killing of Pd is highly specific, with minimal to no impact on the indigenous microbes present in the soil samples. These findings provide the scientific rationale for the field trials of Tp in the WNS-affected hibernacula for the effective decontamination of Pd and the control of WNS.}, } @article {pmid30089517, year = {2018}, author = {Esvaran, M and Conway, PL}, title = {Lactobacilli can attenuate inflammation in mouse macrophages exposed to polyethylene particles in vitro.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {567}, pmid = {30089517}, issn = {1756-0500}, mesh = {Animals ; Cytokines ; *Inflammation ; *Lactobacillus ; Macrophages/*drug effects ; Mice ; Osteolysis ; Polyethylene/toxicity ; Tumor Necrosis Factor-alpha ; }, abstract = {OBJECTIVE: It is well established that polyethylene (PE) wear particles induce macrophage production of cytokines and mediators associated with the pathogenesis of inflammatory osteolysis. The objective of this study was to examine the potential of three Lactobacillus strains to attenuate the TNF-α cytokine response of macrophages exposed to Ceridust 3615 PE particles. An in vitro experimental model using the RAW 246.7 macrophage cell line and PE particles was utilized.

RESULTS: Lactobacillus strains were found to modulate the cytokines in a strain and dose specific manner. Only the Lactobacillus acidophilus strain that was tested was able to attenuate PE particle-induced TNF-α production by RAW 246.7 macrophages. This effect was independent of IL-10 cytokine levels since all three strains of lactobacilli yielded comparable levels of IL-10. It was concluded that some, but not all, Lactobacillus strains may be useful in reducing the risk of inflammatory osteolysis and that further studies in appropriate in vivo models are warranted. Furthermore, this in vitro model can be used to evaluate the inflammatory potential of new materials being tested for use as joint implants.}, } @article {pmid30089471, year = {2018}, author = {Wu, Q and Ni, M and Wang, G and Liu, Q and Yu, M and Tang, J}, title = {Omics for understanding the tolerant mechanism of Trichoderma asperellum TJ01 to organophosphorus pesticide dichlorvos.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {596}, pmid = {30089471}, issn = {1471-2164}, support = {31440025//National Natural Science Foundation of China (CN)/ ; KJ2018A0339//Key Projects of Natural Science Research in Anhui Colleges and Universities/ ; 2018HXXM21//Fuyang Normal University Research Project/ ; 201610371025//National Training Programs of Innovation and Entrepreneurship for Undergraduates/ ; }, mesh = {Chromatography, Liquid ; Dichlorvos/*pharmacology ; *Drug Resistance, Fungal ; Fungal Proteins/drug effects/*genetics ; Gas Chromatography-Mass Spectrometry ; Gene Expression Profiling/methods ; Gene Expression Regulation, Fungal/drug effects ; Metabolome/*drug effects ; Metabolomics/methods ; Pesticides/*pharmacology ; Secondary Metabolism/drug effects ; Sequence Analysis, RNA ; Trichoderma/chemistry/drug effects/genetics/*growth & development ; }, abstract = {BACKGROUD: Though it is toxic to humans, dichlorvos is a widely used chemical pesticide and plays an important role in the control of plant pests. The application of a combination of the biocontrol agent Trichoderma with dichlorvos may reduce the need for chemical pesticides. Therefore, revealing the specific molecular mechanism of Trichoderma tolerance to dichlorvos has become particularly important.

RESULTS: In this study, using transcriptome and metabolome analyses, changes in primary and secondary metabolisms in Trichoderma asperellum TJ01 were comprehensively studied in the presence of dichlorvos. A novel C2H2 zinc finger protein gene, zinc finger chimera 1 (zfc1), was discovered to be upregulated, along with a large number of oxidoreductase genes and ABC transporter genes under dichlorvos stress. In addition, gas chromatography-mass spectrometry (GC-TOF-MS), and liquid chromatography-mass spectrometry (LC-QQQ-MS) data revealed the global primary and secondary metabolic changes that occur in T. asperellum TJ01 under dichlorvos stress.

CONCLUSIONS: The tolerance mechanism of T. asperellum TJ01 to dichlorvos was proposed. In addition, the absorption and residue of dichlorvos were analyzed, laying the foundation for elucidation of the mechanism by which T. asperellum TJ01 degrades pesticide residues.}, } @article {pmid30089468, year = {2018}, author = {Wiesel, Y and Sabath, N and Shalgi, R}, title = {DoGFinder: a software for the discovery and quantification of readthrough transcripts from RNA-seq.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {597}, pmid = {30089468}, issn = {1471-2164}, support = {677776//European Research Council/International ; }, mesh = {Animals ; Cell Hypoxia ; Endothelial Cells/cytology ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Lung/blood supply ; Microvessels/cytology ; Sequence Analysis, RNA/*methods ; *Software ; }, abstract = {BACKGROUND: Recent studies have described a widespread induction of transcriptional readthrough as a consequence of various stress conditions in mammalian cells. This novel phenomenon, initially identified from analysis of RNA-seq data, suggests intriguing new levels of gene expression regulation. However, the mechanism underlying naturally occurring transcriptional readthrough, as well as its regulatory consequences, still remain elusive. Furthermore, the readthrough response to stress has thus far not been investigated outside of mammalian species, and the occurrence of readthrough in many physiological and disease conditions remains to be explored.

RESULTS: To facilitate a wider investigation into transcriptional readthrough, we created the DoGFinder software package, for the streamlined identification and quantification of readthrough transcripts, also known as DoGs (Downstream of Gene-containing transcripts), from any RNA-seq dataset. Using DoGFinder, we explore the dependence of DoG discovery potential on RNA-seq library depth, and show that stress-induced readthrough induction discovery is robust to sequencing depth, and input parameter settings. We further demonstrate the use of the DoGFinder software package on a new publically available RNA-seq dataset, and discover DoG induction in human PME cells following hypoxia - a previously unknown readthrough inducing stress type.

CONCLUSIONS: DoGFinder will enable users to explore, in a few simple steps, the readthrough phenomenon in any condition and organism. DoGFinder is freely available at https://github.com/shalgilab/DoGFinder .}, } @article {pmid30089465, year = {2018}, author = {Oliveira, RRM and Nunes, GL and de Lima, TGL and Oliveira, G and Alves, R}, title = {PIPEBAR and OverlapPER: tools for a fast and accurate DNA barcoding analysis and paired-end assembly.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {297}, pmid = {30089465}, issn = {1471-2105}, support = {443270/2015-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 440880/2013-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)/ ; 307479/2016-1)//Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)/ ; 20/2016//Conselho de Aperfeiçoamento de Pessoal de Nível Superior - CAPES - BR/ ; 22298//Fundação de Desenvolvimento da Pesquisa (BR)/ ; }, abstract = {BACKGROUND: Taxonomic identification of plants and insects is a hard process that demands expert taxonomists and time, and it's often difficult to distinguish on morphology only. DNA barcodes allow a rapid species discovery and identification and have been widely used for taxonomic identification by targeting known gene regions that permit to discriminate these species. DNA barcode sequence analysis is usually carried out with processes and tools that still demand a high interaction with the user or researcher. To reduce at most such interaction, we proposed PIPEBAR, a pipeline for DNA chromatograms analysis of Sanger platform sequencing, ensuring high quality consensus sequences along with efficient running time. We also proposed a paired-end reads assembly tool, OverlapPER, which is used in sequence or independently of PIPEBAR.

RESULTS: PIPEBAR is a command line tool to automatize the processing of large number of trace files. It is accurate as the proprietary Geneious tool and faster than most popular software for barcoding analysis. It is 7 times faster than Geneious and 14 times faster than SeqTrace for processing hundreds of barcoding sequences. OverlapPER is a novel tool for overlapping paired-end reads accurately that accepts both substitution and indel errors and returns both overlapped and non-overlapped regions between a pair of reads. OverlapPER obtained the best results compared to currently used tools when merging 1,000,000 simulated paired-end reads.

CONCLUSIONS: PIPEBAR and OverlapPER run on most operating systems and are freely available, along with supporting code and documentation, at https://sourceforge.net/projects/PIPEBAR / and https://sourceforge.net/projects/overlapper-reads /.}, } @article {pmid30089464, year = {2018}, author = {Lin, IH and Chang, JL and Hua, K and Huang, WC and Hsu, MT and Chen, YF}, title = {Skeletal muscle in aged mice reveals extensive transformation of muscle gene expression.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {55}, pmid = {30089464}, issn = {1471-2156}, support = {MOST 103-2320-B-038-057//Ministry of Science and Technology, Taiwan/ ; MOST 104-2320-B-038-049//Ministry of Science and Technology, Taiwan/ ; MOST105-2320-B-038-022-MY3//Ministry of Science and Technology, Taiwan (TW)/ ; TMU102-AE1-B37//Taipei Medical University/ ; }, abstract = {BACKGROUND: Aging leads to decreased skeletal muscle function in mammals and is associated with a progressive loss of muscle mass, quality and strength. Age-related muscle loss (sarcopenia) is an important health problem associated with the aged population.

RESULTS: We investigated the alteration of genome-wide transcription in mouse skeletal muscle tissue (rectus femoris muscle) during aging using a high-throughput sequencing technique. Analysis revealed significant transcriptional changes between skeletal muscles of mice at 3 (young group) and 24 (old group) months of age. Specifically, genes associated with energy metabolism, cell proliferation, muscle myosin isoforms, as well as immune functions were found to be altered. We observed several interesting gene expression changes in the elderly, many of which have not been reported before.

CONCLUSIONS: Those data expand our understanding of the various compensatory mechanisms that can occur with age, and further will assist in the development of methods to prevent and attenuate adverse outcomes of aging.}, } @article {pmid30089462, year = {2018}, author = {Amaral, ML and Erikson, GA and Shokhirev, MN}, title = {BART: bioinformatics array research tool.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {296}, pmid = {30089462}, issn = {1471-2105}, support = {CCSG 014195//Division of Cancer Epidemiology and Genetics, National Cancer Institute/ ; }, abstract = {BACKGROUND: Microarray experiments comprise more than half of all series in the Gene Expression Omnibus (GEO). However, downloading and analyzing raw or semi-processed microarray data from GEO is not intuitive and requires manual error-prone analysis and a bioinformatics background. This is due to a lack of standardization in array platform fabrication as well as the lack of a simple interactive tool for clustering, plotting, differential expression testing, and testing for functional enrichment.

RESULTS: We introduce the Bioinformatics Array Research Tool (BART), an R Shiny web application that automates the microarray download and analysis process across diverse microarray platforms. It provides an intuitive interface, automatically downloads and parses data from GEO, suggests groupings of samples for differential expression testing, performs batch effect correction, outputs quality control plots, converts probe IDs, generates full lists of differentially expressed genes, and performs functional enrichment analysis. We show that BART enables a more comprehensive analysis of a wider range of microarray datasets on GEO by comparing it to four leading online microarray analysis tools.

CONCLUSIONS: BART allows a scientist with no bioinformatics background to extract knowledge from their own microarray data or microarray experiments available from GEO. BART is functional on more microarray experiments and provides more comprehensive analyses than extant microarray analysis tools. BART is hosted on bart.salk.edu , includes a user tutorial, and is available for download from https://bitbucket.org/Luisa_amaral/bart .}, } @article {pmid30089455, year = {2018}, author = {Chen, LM and Yao, N and Garg, E and Zhu, Y and Nguyen, TTT and Pokhvisneva, I and Hari Dass, SA and Unternaehrer, E and Gaudreau, H and Forest, M and McEwen, LM and MacIsaac, JL and Kobor, MS and Greenwood, CMT and Silveira, PP and Meaney, MJ and O'Donnell, KJ}, title = {PRS-on-Spark (PRSoS): a novel, efficient and flexible approach for generating polygenic risk scores.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {295}, pmid = {30089455}, issn = {1471-2105}, abstract = {BACKGROUND: Polygenic risk scores (PRS) describe the genomic contribution to complex phenotypes and consistently account for a larger proportion of variance in outcome than single nucleotide polymorphisms (SNPs) alone. However, there is little consensus on the optimal data input for generating PRS, and existing approaches largely preclude the use of imputed posterior probabilities and strand-ambiguous SNPs i.e., A/T or C/G polymorphisms. Our ability to predict complex traits that arise from the additive effects of a large number of SNPs would likely benefit from a more inclusive approach.

RESULTS: We developed PRS-on-Spark (PRSoS), a software implemented in Apache Spark and Python that accommodates different data inputs and strand-ambiguous SNPs to calculate PRS. We compared performance between PRSoS and an existing software (PRSice v1.25) for generating PRS for major depressive disorder using a community cohort (N = 264). We found PRSoS to perform faster than PRSice v1.25 when PRS were generated for a large number of SNPs (~ 17 million SNPs; t = 42.865, p = 5.43E-04). We also show that the use of imputed posterior probabilities and the inclusion of strand-ambiguous SNPs increase the proportion of variance explained by a PRS for major depressive disorder (from 4.3% to 4.8%).

CONCLUSIONS: PRSoS provides the user with the ability to generate PRS using an inclusive and efficient approach that considers a larger number of SNPs than conventional approaches. We show that a PRS for major depressive disorder that includes strand-ambiguous SNPs, calculated using PRSoS, accounts for the largest proportion of variance in symptoms of depression in a community cohort, demonstrating the utility of this approach. The availability of this software will help users develop more informative PRS for a variety of complex phenotypes.}, } @article {pmid30089300, year = {2018}, author = {Liehr, T and Hamid Al-Rikabi, AB}, title = {Impaired Spermatogenesis due to Small Supernumerary Marker Chromosomes: The Reason for Infertility Is Only Reliably Ascertainable by Cytogenetics.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000491870}, pmid = {30089300}, issn = {1661-5433}, abstract = {Infertile male with small supernumerary marker chromosomes (sSMCs) were studied. Overall, 37 own patients and 166 cases from the literature were included. sSMCs of our own cases were characterized by multicolor-FISH probe sets. Available clinical data of the infertile males were also evaluated, and meta-analysis on suitability of molecular karyotyping for sSMC characterization was done. As a result, sSMCs can be optimally characterized by single-cell directed (molecular) cytogenetics. In infertile males, sSMCs derive predominantly from one of the acrocentric chromosomes, mainly chromosomes 15, 14, and 22. Interestingly, altered spermiograms were found in 62% of the males with an sSMC, while the remainder cases had infertility in connection with recurrent spontaneous abortions. Meta-analysis for detectability of sSMCs by aCGH revealed that 81-87% of the cases would have not been picked up by exclusive use of that approach. Thus, as impaired spermatogenesis is known to be indicative for gross chromosomal anomalies in infertile male patients, it can be concluded from this study that the presence of sSMCs also needs to be considered. However, sSMCs can only be reliably detected by standard karyotyping and not by modern high throughput approaches like aCGH and next-generation sequencing.}, } @article {pmid30089226, year = {2019}, author = {Harris, PM and Diaz, MR and Eberli, GP}, title = {The Formation and Distribution of Modern Ooids on Great Bahama Bank.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {491-516}, doi = {10.1146/annurev-marine-010318-095251}, pmid = {30089226}, issn = {1941-0611}, abstract = {Great Bahama Bank (GBB) is the principal location of the formation and accumulation of ooids (concentrically coated, sand-size carbonate grains) in the world today, and as such has been the focus of studies on all aspects of ooids for more than half a century. Our view from a close look at this vast body of literature coupled with our continuing interests stresses that biological mechanisms (microbially mediated organomineralization) are very important in the formation of ooids, whereas the controlling factor for the distribution and size of ooid sand bodies is the physical energy. Mapping and coring studies of the modern ooid sand bodies on GBB provide insight into the rock record from different perspectives. An important consequence of the dual influence of ooid formation and distribution is that the geochemical signature of ooids is not in equilibrium with the seawater in which ooids form; therefore, extracting the paleophysical energy record from oolitic deposits is potentially more accurate than doing so for the paleochemical record.}, } @article {pmid30089222, year = {2018}, author = {Gudipaty, SA and Conner, CM and Rosenblatt, J and Montell, DJ}, title = {Unconventional Ways to Live and Die: Cell Death and Survival in Development, Homeostasis, and Disease.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {311-332}, doi = {10.1146/annurev-cellbio-100616-060748}, pmid = {30089222}, issn = {1530-8995}, abstract = {Balancing cell death and survival is essential for normal development and homeostasis and for preventing diseases, especially cancer. Conventional cell death pathways include apoptosis, a form of programmed cell death controlled by a well-defined biochemical pathway, and necrosis, the lysis of acutely injured cells. New types of regulated cell death include necroptosis, pyroptosis, ferroptosis, phagoptosis, and entosis. Autophagy can promote survival or can cause death. Newly described processes of anastasis and resuscitation show that, remarkably, cells can recover from the brink of apoptosis or necroptosis. Important new work shows that epithelia achieve homeostasis by extruding excess cells, which then die by anoikis due to loss of survival signals. This mechanically regulated process both maintains barrier function as cells die and matches rates of proliferation and death. In this review, we describe these unconventional ways in which cells have evolved to die or survive, as well as the contributions that these processes make to homeostasis and cancer.}, } @article {pmid30089221, year = {2018}, author = {Hammond, TR and Robinton, D and Stevens, B}, title = {Microglia and the Brain: Complementary Partners in Development and Disease.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {523-544}, doi = {10.1146/annurev-cellbio-100616-060509}, pmid = {30089221}, issn = {1530-8995}, abstract = {An explosion of findings driven by powerful new technologies has expanded our understanding of microglia, the resident immune cells of the central nervous system (CNS). This wave of discoveries has fueled a growing interest in the roles that these cells play in the development of the CNS and in the neuropathology of a diverse array of disorders. In this review, we discuss the crucial roles that microglia play in shaping the brain-from their influence on neurons and glia within the developing CNS to their roles in synaptic maturation and brain wiring-as well as some of the obstacles to overcome when assessing their contributions to normal brain development. Furthermore, we examine how normal developmental functions of microglia are perturbed or remerge in neurodevelopmental and neurodegenerative disease.}, } @article {pmid30088343, year = {2018}, author = {Stahl, D}, title = {Editorial.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14298}, pmid = {30088343}, issn = {1462-2920}, } @article {pmid30087774, year = {2018}, author = {Huijben, S and Chan, BHK and Nelson, WA and Read, AF}, title = {The impact of within-host ecology on the fitness of a drug-resistant parasite.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {127-137}, pmid = {30087774}, issn = {2050-6201}, support = {R01 AI089819/AI/NIAID NIH HHS/United States ; R01 GM089932/GM/NIGMS NIH HHS/United States ; U19 AI089676/AI/NIAID NIH HHS/United States ; }, abstract = {Background and objectives: The rate of evolution of drug resistance depends on the fitness of resistant pathogens. The fitness of resistant pathogens is reduced by competition with sensitive pathogens in untreated hosts and so enhanced by competitive release in drug-treated hosts. We set out to estimate the magnitude of those effects on a variety of fitness measures, hypothesizing that competitive suppression and competitive release would have larger impacts when resistance was rarer to begin with. Methodology: We infected mice with varying densities of drug-resistant Plasmodium chabaudi malaria parasites in a fixed density of drug-sensitive parasites and followed infection dynamics using strain-specific quantitative PCR. Results: Competition with susceptible parasites reduced the absolute fitness of resistant parasites by 50-100%. Drug treatment increased the absolute fitness from 2- to >10 000-fold. The ecological context and choice of fitness measure was responsible for the wide variation in those estimates. Initial population growth rates poorly predicted parasite abundance and transmission probabilities. Conclusions and implications: (i) The sensitivity of estimates of pathogen fitness to ecological context and choice of fitness measure make it difficult to derive field-relevant estimates of the fitness costs and benefits of resistance from experimental settings. (ii) Competitive suppression can be a key force preventing resistance from emerging when it is rare, as it is when it first arises. (iii) Drug treatment profoundly affects the fitness of resistance. Resistance evolution could be slowed by developing drug use policies that consider in-host competition.}, } @article {pmid30087486, year = {2018}, author = {Del Bello, L}, title = {Indian scientists race to map Ganges river in 3D.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {149-150}, doi = {10.1038/d41586-018-05872-w}, pmid = {30087486}, issn = {1476-4687}, } @article {pmid30087485, year = {2018}, author = {Willyard, C}, title = {The mice with human tumours: Growing pains for a popular cancer model.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {156-157}, doi = {10.1038/d41586-018-05890-8}, pmid = {30087485}, issn = {1476-4687}, mesh = {Aged ; Animals ; Cell Line, Tumor ; Female ; Humans ; Immunotherapy ; Medical Oncology/methods/trends ; Mice ; Precision Medicine/*methods/*trends ; *Xenograft Model Antitumor Assays ; }, } @article {pmid30087484, year = {2018}, author = {Franke, KJ and von Oppen, F}, title = {Topological states engineered in narrow strips of graphene.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {175-176}, doi = {10.1038/d41586-018-05851-1}, pmid = {30087484}, issn = {1476-4687}, mesh = {Engineering ; *Graphite ; *Nanotubes, Carbon ; }, } @article {pmid30087483, year = {2018}, author = {Margulis, W}, title = {Integration of optoelectronics into fibres enhances textiles.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {170-171}, doi = {10.1038/d41586-018-05873-9}, pmid = {30087483}, issn = {1476-4687}, mesh = {*Textiles ; }, } @article {pmid30087482, year = {2018}, author = {Gewin, V}, title = {Earth hacker.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {273}, doi = {10.1038/d41586-018-05897-1}, pmid = {30087482}, issn = {1476-4687}, } @article {pmid30087481, year = {2018}, author = {Gogarty, B}, title = {Glacier geoengineering needs lawyers too.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {167}, doi = {10.1038/d41586-018-05877-5}, pmid = {30087481}, issn = {1476-4687}, mesh = {Environmental Policy ; Global Warming ; *Ice Cover ; *International Cooperation ; }, } @article {pmid30087480, year = {2018}, author = {David, D and Markó, B}, title = {Don't decouple Romanian universities from international excellence.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {167}, doi = {10.1038/d41586-018-05876-6}, pmid = {30087480}, issn = {1476-4687}, } @article {pmid30087479, year = {2018}, author = {Vidal, E and Thibault, M and Bourgeois, K}, title = {Warnings alone won't protect New Caledonia wildlife from cruises.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {167}, doi = {10.1038/d41586-018-05878-4}, pmid = {30087479}, issn = {1476-4687}, mesh = {Animals ; Animals, Wild ; *Birds ; *Fishes ; New Caledonia ; Seafood ; }, } @article {pmid30087478, year = {2018}, author = {Yang, H and Flower, RJ and Thompson, JR}, title = {Eradicate illicit production of ozone-depleting emissions.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {167}, doi = {10.1038/d41586-018-05879-3}, pmid = {30087478}, issn = {1476-4687}, } @article {pmid30087477, year = {2018}, author = {Kwok, R}, title = {How to work with your institution's press office to maximize the reach of your work.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {271-273}, doi = {10.1038/d41586-018-05896-2}, pmid = {30087477}, issn = {1476-4687}, } @article {pmid30087476, year = {2018}, author = {}, title = {A single island spawned two populations of miniature humans.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {145}, doi = {10.1038/d41586-018-05881-9}, pmid = {30087476}, issn = {1476-4687}, } @article {pmid30087475, year = {2018}, author = {Schiermeier, Q}, title = {Gigantic review of German science recommends more data and diversity.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {153-154}, doi = {10.1038/d41586-018-05818-2}, pmid = {30087475}, issn = {1476-4687}, mesh = {Biomedical Research/standards/trends ; Datasets as Topic ; Foreign Professional Personnel/*supply & distribution ; Germany ; Humans ; Internationality ; Personnel Selection ; Science/standards/*trends ; Sexism/*prevention & control ; Workforce ; }, } @article {pmid30087474, year = {2018}, author = {}, title = {How to get droplets just right.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {144}, doi = {10.1038/d41586-018-05868-6}, pmid = {30087474}, issn = {1476-4687}, } @article {pmid30087473, year = {2018}, author = {}, title = {Transport network's handrails teem with a mix of microbes during evening rush hour.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {145}, doi = {10.1038/d41586-018-05855-x}, pmid = {30087473}, issn = {1476-4687}, } @article {pmid30087472, year = {2018}, author = {Castelvecchi, D}, title = {Number-theory prodigy among winners of most coveted prize in mathematics.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {152-153}, doi = {10.1038/d41586-018-05864-w}, pmid = {30087472}, issn = {1476-4687}, } @article {pmid30087471, year = {2018}, author = {}, title = {These insects vomit collectively to defend themselves.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {144-145}, doi = {10.1038/d41586-018-05853-z}, pmid = {30087471}, issn = {1476-4687}, } @article {pmid30087470, year = {2018}, author = {Reardon, S and Witze, A}, title = {The wait is over: Trump taps meteorologist as White House science adviser.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {150-151}, doi = {10.1038/d41586-018-05862-y}, pmid = {30087470}, issn = {1476-4687}, } @article {pmid30087469, year = {2018}, author = {}, title = {Hunger's toll looks set to grow with tough action on climate change.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {144}, doi = {10.1038/d41586-018-05837-z}, pmid = {30087469}, issn = {1476-4687}, } @article {pmid30087468, year = {2018}, author = {}, title = {Volcanoes hinder global pact to protect the planet.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {145}, doi = {10.1038/d41586-018-05833-3}, pmid = {30087468}, issn = {1476-4687}, } @article {pmid30087467, year = {2018}, author = {}, title = {Enormous penguin population crashes by almost 90.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {144}, doi = {10.1038/d41586-018-05850-2}, pmid = {30087467}, issn = {1476-4687}, } @article {pmid30087441, year = {2018}, author = {Small, KS and Todorčević, M and Civelek, M and El-Sayed Moustafa, JS and Wang, X and Simon, MM and Fernandez-Tajes, J and Mahajan, A and Horikoshi, M and Hugill, A and Glastonbury, CA and Quaye, L and Neville, MJ and Sethi, S and Yon, M and Pan, C and Che, N and Vinuela, A and Tsai, PC and Nag, A and Buil, A and Thorleifsson, G and Raghavan, A and Ding, Q and Morris, AP and Bell, JT and Thorsteinsdottir, U and Stefansson, K and Laakso, M and Dahlman, I and Arner, P and Gloyn, AL and Musunuru, K and Lusis, AJ and Cox, RD and Karpe, F and McCarthy, MI}, title = {Author Correction: Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1342}, doi = {10.1038/s41588-018-0180-2}, pmid = {30087441}, issn = {1546-1718}, abstract = {In the version of this article originally published, minus signs were missing from the three β-values for BMI given in Table 1. The errors have been corrected in the HTML and PDF versions of the article.}, } @article {pmid30087210, year = {2018}, author = {Eyal, N and Lipsitch, M and Bärnighausen, T and Wikler, D}, title = {Opinion: Risk to study nonparticipants: A procedural approach.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8051-8053}, pmid = {30087210}, issn = {1091-6490}, support = {208766/Z/17/Z//Wellcome Trust/United Kingdom ; R01 HD084233/HD/NICHD NIH HHS/United States ; R01 AI114617/AI/NIAID NIH HHS/United States ; R01 AI124389/AI/NIAID NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Attitude ; *Ethics, Research ; Humans ; *Patient Compliance ; Research/*standards ; Research Personnel/psychology ; Risk ; Self-Control ; Surveys and Questionnaires/standards ; }, } @article {pmid30087191, year = {2018}, author = {Yoshida, GJ}, title = {Molecular machinery underlying the autophagic regulation by MDA-9/Syntenin leading to anoikis resistance of tumor cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7652-E7653}, pmid = {30087191}, issn = {1091-6490}, mesh = {*Anoikis ; Autophagy ; Cell Line, Tumor ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Syntenins/*genetics ; }, } @article {pmid30087190, year = {2018}, author = {Talukdar, S and Das, SK and Emdad, L and Sarkar, D and Cavenee, WK and Fisher, PB}, title = {Reply to Yoshida: Delineating critical roles of MDA-9 in protective autophagy-mediated anoikis resistance in human glioma stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7654-E7655}, pmid = {30087190}, issn = {1091-6490}, mesh = {*Anoikis ; *Autophagy ; Cell Line, Tumor ; Glioma ; Humans ; Neoplastic Stem Cells ; }, } @article {pmid30087189, year = {2018}, author = {Abat, C and Gautret, P and Raoult, D}, title = {Benefits of antibiotics burden in low-income countries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8109-E8110}, pmid = {30087189}, issn = {1091-6490}, mesh = {*Anti-Bacterial Agents ; Developing Countries ; Global Health ; Income ; *Poverty ; }, } @article {pmid30087188, year = {2018}, author = {Klein, EY and Levin, SA and Laxminarayan, R}, title = {Reply to Abat et al.: Improved policies necessary to ensure an effective future for antibiotics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {E8111-E8112}, pmid = {30087188}, issn = {1091-6490}, mesh = {*4-Aminobutyrate Transaminase ; *Anti-Bacterial Agents ; }, } @article {pmid30087187, year = {2018}, author = {Santis, CT and Vilenchik, Y and Satyan, N and Rakuljic, G and Yariv, A}, title = {Quantum control of phase fluctuations in semiconductor lasers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7896-E7904}, pmid = {30087187}, issn = {1091-6490}, abstract = {Few laser systems allow access to the light-emitter interaction as versatile and direct as that afforded by semiconductor lasers. Such a level of access can be exploited for the control of the coherence and dynamic properties of the laser. Here, we demonstrate, theoretically and experimentally, the reduction of the quantum phase noise of a semiconductor laser through the direct control of the spontaneous emission into the laser mode, exercised via the precise and deterministic manipulation of the optical mode's spatial field distribution. Central to the approach is the recognition of the intimate interplay between spontaneous emission and optical loss. A method of leveraging and "walking" this fine balance to its limit is described. As a result, some two orders of magnitude reduction in quantum noise over the state of the art in semiconductor lasers, corresponding to a minimum linewidth of [Formula: see text], is demonstrated. Further implications, including an additional order-of-magnitude enhancement in effective coherence by way of control of the relaxation oscillation resonance frequency and enhancement of the intrinsic immunity to optical feedback, highlight the potential of the proposed concept for next-generation, integrated coherent systems.}, } @article {pmid30087186, year = {2018}, author = {Large, AM and Vogler, NW and Canto-Bustos, M and Friason, FK and Schick, P and Oswald, AM}, title = {Differential inhibition of pyramidal cells and inhibitory interneurons along the rostrocaudal axis of anterior piriform cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8067-E8076}, pmid = {30087186}, issn = {1091-6490}, support = {R01 DC015139/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; GABAergic Neurons/cytology/metabolism ; Interneurons/cytology/*metabolism ; Mice ; Mice, Transgenic ; Olfactory Perception/*physiology ; Piriform Cortex/cytology/*metabolism ; Pyramidal Cells/cytology/*metabolism ; Synapses/metabolism ; Synaptic Transmission/*physiology ; }, abstract = {The spatial representation of stimuli in sensory neocortices provides a scaffold for elucidating circuit mechanisms underlying sensory processing. However, the anterior piriform cortex (APC) lacks topology for odor identity as well as afferent and intracortical excitation. Consequently, olfactory processing is considered homogenous along the APC rostral-caudal (RC) axis. We recorded excitatory and inhibitory neurons in APC while optogenetically activating GABAergic interneurons along the RC axis. In contrast to excitation, we find opposing, spatially asymmetric inhibition onto pyramidal cells (PCs) and interneurons. PCs are strongly inhibited by caudal stimulation sites, whereas interneurons are strongly inhibited by rostral sites. At least two mechanisms underlie spatial asymmetries. Enhanced caudal inhibition of PCs is due to increased synaptic strength, whereas rostrally biased inhibition of interneurons is mediated by increased somatostatin-interneuron density. Altogether, we show differences in rostral and caudal inhibitory circuits in APC that may underlie spatial variation in odor processing along the RC axis.}, } @article {pmid30087185, year = {2018}, author = {He, L and Gu, W and Wang, M and Chang, X and Sun, X and Zhang, Y and Lin, X and Yan, C and Fan, W and Su, P and Wang, Y and Yi, C and Lin, G and Li, L and Jiang, Y and Lu, J and Dong, C and Wang, H and Sun, B}, title = {Extracellular matrix protein 1 promotes follicular helper T cell differentiation and antibody production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8621-8626}, pmid = {30087185}, issn = {1091-6490}, mesh = {Animals ; *Antibody Formation ; B-Lymphocytes/cytology/*immunology ; Cell Differentiation/genetics/*immunology ; Extracellular Matrix Proteins/genetics/*immunology ; Influenza A virus/immunology ; Interleukin-6/genetics/immunology ; Interleukins/genetics/immunology ; Mice ; Mice, Knockout ; Orthomyxoviridae Infections/genetics/immunology ; T-Lymphocytes, Helper-Inducer/cytology/*immunology ; }, abstract = {T-follicular helper (TFH) cells are a subset of CD4+ helper T cells that help germinal center (GC) B-cell differentiation and high-affinity antibody production during germinal center reactions. Whether important extracellular molecules control TFH differentiation is not fully understood. Here, we demonstrate that a secreted protein extracellular matrix protein 1 (ECM1) is critical for TFH differentiation and antibody response. A lack of ECM1 inhibited TFH cell development and impaired GC B-cell reactions and antigen-specific antibody production in an antigen-immunized mouse model. ECM1 was induced by IL-6 and IL-21 in TFH cells, promoting TFH differentiation by down-regulating the level of STAT5 phosphorylation and up-regulating Bcl6 expression. Furthermore, injection of recombinant ECM1 protein into mice infected with PR8 influenza virus promoted protective immune responses effectively, by enhancing TFH differentiation and neutralizing antibody production. Collectively, our data identify ECM1 as a soluble protein to promote TFH cell differentiation and antibody production.}, } @article {pmid30087184, year = {2018}, author = {Hsu, WC and Chen, MY and Hsu, SC and Huang, LR and Kao, CY and Cheng, WH and Pan, CH and Wu, MS and Yu, GY and Hung, MS and Leu, CM and Tan, TH and Su, YW}, title = {DUSP6 mediates T cell receptor-engaged glycolysis and restrains TFH cell differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8027-E8036}, pmid = {30087184}, issn = {1091-6490}, mesh = {Animals ; Antibody Formation/physiology ; CD28 Antigens/genetics/immunology/metabolism ; Cell Differentiation/*physiology ; *Dual Specificity Phosphatase 6/genetics/immunology/metabolism ; Glycolysis/*physiology ; Immunoglobulin G/immunology/metabolism ; Interleukins/genetics/immunology/metabolism ; MAP Kinase Kinase 4/genetics/immunology/metabolism ; Mice ; Mice, Knockout ; Mitochondria/genetics/immunology/metabolism ; Oxygen Consumption/physiology ; *Receptors, Antigen, T-Cell/genetics/immunology/metabolism ; Signal Transduction/*physiology ; *T-Lymphocytes, Helper-Inducer/cytology/immunology/metabolism ; p38 Mitogen-Activated Protein Kinases/genetics/immunology/metabolism ; }, abstract = {Activated T cells undergo metabolic reprogramming and effector-cell differentiation but the factors involved are unclear. Utilizing mice lacking DUSP6 (DUSP6-/-), we show that this phosphatase regulates T cell receptor (TCR) signaling to influence follicular helper T (TFH) cell differentiation and T cell metabolism. In vitro, DUSP6-/- CD4+ TFH cells produced elevated IL-21. In vivo, TFH cells were increased in DUSP6-/- mice and in transgenic OTII-DUSP6-/- mice at steady state. After immunization, DUSP6-/- and OTII-DUSP6-/- mice generated more TFH cells and produced more antigen-specific IgG2 than controls. Activated DUSP6-/- T cells showed enhanced JNK and p38 phosphorylation but impaired glycolysis. JNK or p38 inhibitors significantly reduced IL-21 production but did not restore glycolysis. TCR-stimulated DUSP6-/- T cells could not induce phosphofructokinase activity and relied on glucose-independent fueling of mitochondrial respiration. Upon CD28 costimulation, activated DUSP6-/- T cells did not undergo the metabolic commitment to glycolysis pathway to maintain viability. Unexpectedly, inhibition of fatty acid oxidation drastically lowered IL-21 production in DUSP6-/- TFH cells. Our findings suggest that DUSP6 connects TCR signaling to activation-induced metabolic commitment toward glycolysis and restrains TFH cell differentiation via inhibiting IL-21 production.}, } @article {pmid30087183, year = {2018}, author = {Kong, D and Zhang, K and Schubert, G and Anderson, JD}, title = {Origin of Jupiter's cloud-level zonal winds remains a puzzle even after Juno.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8499-8504}, pmid = {30087183}, issn = {1091-6490}, abstract = {How far Jupiter's cloud-level zonal winds penetrate into its interior, a question related to the origin of the winds, has long been a major puzzle about Jupiter. There exist two different views: the shallow scenario in which the cloud-level winds are confined within the thin weather layer at cloud top and the deep scenario in which the cloud-level winds manifest thermal convection in the deep interior. We interpret, using two different models corresponding to the two scenarios, the high-precision measurements of Jupiter's equatorially antisymmetric gravitational field by the Juno spacecraft. We demonstrate, based on the thermal-gravitational wind equation, that both the shallow and deep cloud-level winds models are capable of explaining the measured odd gravitational coefficients within the measured uncertainties, reflecting the nonunique nature of the gravity inverse problem. We conclude that the high-precision Juno gravity measurements cannot provide an answer to the long-standing question about the origin of Jupiter's cloud-level zonal winds.}, } @article {pmid30087182, year = {2018}, author = {Powers, MJ and Trent, MS}, title = {Phospholipid retention in the absence of asymmetry strengthens the outer membrane permeability barrier to last-resort antibiotics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8518-E8527}, pmid = {30087182}, issn = {1091-6490}, mesh = {Acinetobacter baumannii/genetics/*metabolism ; Bacterial Outer Membrane Proteins/genetics/*metabolism ; Cell Membrane/genetics/*metabolism ; Cell Membrane Permeability/*physiology ; Lipid A/genetics/*metabolism ; Lipopolysaccharides/genetics/*metabolism ; }, abstract = {The outer membrane of Gram-negative bacteria is a critical barrier that prevents entry of noxious compounds. Integral to this functionality is the presence of lipopolysaccharide (LPS) or lipooligosaccharide (LOS), a molecule that is located exclusively in the outer leaflet of the outer membrane. Its lipid anchor, lipid A, is a glycolipid whose hydrophobicity and net negative charge are primarily responsible for the robustness of the membrane. Because of this, lipid A is a hallmark of Gram-negative physiology and is generally essential for survival. Rare exceptions have been described, including Acinetobacter baumannii, which can survive in the absence of lipid A, albeit with significant growth and membrane permeability defects. Here, we show by an evolution experiment that LOS-deficient A. baumannii can rapidly improve fitness over the course of only 120 generations. We identified two factors which negatively contribute to fitness in the absence of LOS, Mla and PldA. These proteins are involved in glycerophospholipid transport (Mla) and lipid degradation (PldA); both are active only on mislocalized, surface-exposed glycerophospholipids. Elimination of these two mechanisms was sufficient to cause a drastic fitness improvement in LOS-deficient A. baumannii The LOS-deficient double mutant grows as robustly as LOS-positive wild-type bacteria while remaining resistant to the last-resort polymyxin antibiotics. These data provide strong biological evidence for the directionality of Mla-mediated glycerophospholipid transport in Gram-negative bacteria and furthers our knowledge of asymmetry-maintenance mechanisms in the context of the outer membrane barrier.}, } @article {pmid30087181, year = {2018}, author = {Litvinov, RI and Kononova, O and Zhmurov, A and Marx, KA and Barsegov, V and Thirumalai, D and Weisel, JW}, title = {Regulatory element in fibrin triggers tension-activated transition from catch to slip bonds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8575-8580}, pmid = {30087181}, issn = {1091-6490}, support = {R01 GM089685/GM/NIGMS NIH HHS/United States ; R01 HL135254/HL/NHLBI NIH HHS/United States ; U01 HL116330/HL/NHLBI NIH HHS/United States ; }, mesh = {Binding Sites ; Calcium/*chemistry/metabolism ; Fibrin/*chemistry/metabolism ; Humans ; Multiprotein Complexes/*chemistry/metabolism ; }, abstract = {Fibrin formation and mechanical stability are essential in thrombosis and hemostasis. To reveal how mechanical load impacts fibrin, we carried out optical trap-based single-molecule forced unbinding experiments. The strength of noncovalent A:a knob-hole bond stabilizing fibrin polymers first increases with tensile force (catch bonds) and then decreases with force when the force exceeds a critical value (slip bonds). To provide the structural basis of catch-slip-bond behavior, we analyzed crystal structures and performed molecular modeling of A:a knob-hole complex. The movable flap (residues γ295 to γ305) containing the weak calcium-binding site γ2 serves as a tension sensor. Flap dissociation from the B domain in the γ-nodule and translocation to knob 'A' triggers hole 'a' closure, resulting in the increase of binding affinity and prolonged bond lifetimes. The discovery of biphasic kinetics of knob-hole bond rupture is quantitatively explained by using a theory, formulated in terms of structural transitions in the binding pocket between the low-affinity (slip) and high-affinity (catch) states. We provide a general framework to understand the mechanical response of protein pairs capable of tension-induced remodeling of their association interface. Strengthening of the A:a knob-hole bonds at 30- to 40-pN forces might favor formation of nascent fibrin clots subject to hydrodynamic shear in vivo.}, } @article {pmid30087180, year = {2018}, author = {Lundquist, K and Bakelar, J and Noinaj, N and Gumbart, JC}, title = {C-terminal kink formation is required for lateral gating in BamA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7942-E7949}, pmid = {30087180}, issn = {1091-6490}, support = {F32 GM121021/GM/NIGMS NIH HHS/United States ; K22 AI113078/AI/NIAID NIH HHS/United States ; R01 GM116961/GM/NIGMS NIH HHS/United States ; R01 GM123169/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Outer Membrane Proteins/*chemistry/metabolism ; Escherichia coli/*chemistry/metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; *Molecular Dynamics Simulation ; Protein Domains ; Protein Structure, Secondary ; Structure-Activity Relationship ; }, abstract = {In Gram-negative bacteria, the outer membrane contains primarily β-barrel transmembrane proteins and lipoproteins. The insertion and assembly of β-barrel outer-membrane proteins (OMPs) is mediated by the β-barrel assembly machinery (BAM) complex, the core component of which is the 16-stranded transmembrane β-barrel BamA. Recent studies have indicated a possible role played by the seam between the first and last β-barrel strands of BamA in the OMP insertion process through lateral gating and a destabilized membrane region. In this study, we have determined the stability and dynamics of the lateral gate through over 12.5 μs of equilibrium simulations and 4 μs of free-energy calculations. From the equilibrium simulations, we have identified a persistent kink in the C-terminal strand and observed spontaneous lateral-gate separation in a mimic of the native bacterial outer membrane. Free-energy calculations of lateral gate opening revealed a significantly lower barrier to opening in the C-terminal kinked conformation; mutagenesis experiments confirm the relevance of C-terminal kinking to BamA structure and function.}, } @article {pmid30086797, year = {2018}, author = {Dalcin Martins, P and Danczak, RE and Roux, S and Frank, J and Borton, MA and Wolfe, RA and Burris, MN and Wilkins, MJ}, title = {Viral and metabolic controls on high rates of microbial sulfur and carbon cycling in wetland ecosystems.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {138}, pmid = {30086797}, issn = {2049-2618}, mesh = {Bacteria/classification/*metabolism/virology ; Carbon/*metabolism ; DNA, Ribosomal/genetics ; Geologic Sediments/*microbiology ; High-Throughput Nucleotide Sequencing ; Metagenomics/*methods ; North America ; Oxidation-Reduction ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfur/*metabolism ; Viruses/*classification ; Wetlands ; }, abstract = {BACKGROUND: Microorganisms drive high rates of methanogenesis and carbon mineralization in wetland ecosystems. These signals are especially pronounced in the Prairie Pothole Region of North America, the tenth largest wetland ecosystem in the world. Sulfate reduction rates up to 22 μmol cm-3 day-1 have been measured in these wetland sediments, as well as methane fluxes up to 160 mg m-2 h-1-some of the highest emissions ever measured in North American wetlands. While pore waters from PPR wetlands are characterized by high concentrations of sulfur species and dissolved organic carbon, the constraints on microbial activity are poorly understood. Here, we utilized metagenomics to investigate candidate sulfate reducers and methanogens in this ecosystem and identify metabolic and viral controls on microbial activity.

RESULTS: We recovered 162 dsrA and 206 dsrD sequences from 18 sediment metagenomes and reconstructed 24 candidate sulfate reducer genomes assigned to seven phyla. These genomes encoded the potential for utilizing a wide variety of electron donors, such as methanol and other alcohols, methylamines, and glycine betaine. We also identified 37 mcrA sequences spanning five orders and recovered two putative methanogen genomes representing the most abundant taxa-Methanosaeta and Methanoregulaceae. However, given the abundance of Methanofollis-affiliated mcrA sequences, the detection of F420-dependent alcohol dehydrogenases, and millimolar concentrations of ethanol and 2-propanol in sediment pore fluids, we hypothesize that these alcohols may drive a significant fraction of methanogenesis in this ecosystem. Finally, extensive viral novelty was detected, with approximately 80% of viral populations being unclassified at any known taxonomic levels and absent from publicly available databases. Many of these viral populations were predicted to target dominant sulfate reducers and methanogens.

CONCLUSIONS: Our results indicate that diversity is likely key to extremely high rates of methanogenesis and sulfate reduction observed in these wetlands. The inferred genomic diversity and metabolic versatility could result from dynamic environmental conditions, viral infections, and niche differentiation in the heterogeneous sediment matrix. These processes likely play an important role in modulating carbon and sulfur cycling in this ecosystem.}, } @article {pmid30086749, year = {2018}, author = {Krefting, J and Andrade-Navarro, MA and Ibn-Salem, J}, title = {Evolutionary stability of topologically associating domains is associated with conserved gene regulation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {87}, pmid = {30086749}, issn = {1741-7007}, abstract = {BACKGROUND: The human genome is highly organized in the three-dimensional nucleus. Chromosomes fold locally into topologically associating domains (TADs) defined by increased intra-domain chromatin contacts. TADs contribute to gene regulation by restricting chromatin interactions of regulatory sequences, such as enhancers, with their target genes. Disruption of TADs can result in altered gene expression and is associated to genetic diseases and cancers. However, it is not clear to which extent TAD regions are conserved in evolution and whether disruption of TADs by evolutionary rearrangements can alter gene expression.

RESULTS: Here, we hypothesize that TADs represent essential functional units of genomes, which are stable against rearrangements during evolution. We investigate this using whole-genome alignments to identify evolutionary rearrangement breakpoints of different vertebrate species. Rearrangement breakpoints are strongly enriched at TAD boundaries and depleted within TADs across species. Furthermore, using gene expression data across many tissues in mouse and human, we show that genes within TADs have more conserved expression patterns. Disruption of TADs by evolutionary rearrangements is associated with changes in gene expression profiles, consistent with a functional role of TADs in gene expression regulation.

CONCLUSIONS: Together, these results indicate that TADs are conserved building blocks of genomes with regulatory functions that are often reshuffled as a whole instead of being disrupted by rearrangements.}, } @article {pmid30086736, year = {2018}, author = {Rowland, MA and Wear, H and Watanabe, KH and Gust, KA and Mayo, ML}, title = {Statistical relationship between metabolic decomposition and chemical uptake predicts bioconcentration factor data for diverse chemical exposures.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {81}, pmid = {30086736}, issn = {1752-0509}, abstract = {BACKGROUND: A challenge of in vitro to in vivo extrapolation (IVIVE) is to predict the physical state of organisms exposed to chemicals in the environment from in vitro exposure assay data. Although toxicokinetic modeling approaches promise to bridge in vitro screening data with in vivo effects, they are often encumbered by a need for redesign or re-parameterization when applied to different tissues or chemicals.

RESULTS: We demonstrate a parameterization of reverse toxicokinetic (rTK) models developed for the adult zebrafish (Danio rerio) based upon particle swarm optimizations (PSO) of the chemical uptake and degradation rates that predict bioconcentration factors (BCF) for a broad range of chemicals. PSO reveals a relationship between chemical uptake and decomposition parameter values that predicts chemical-specific BCF values with moderate statistical agreement to a limited yet diverse chemical dataset, and all without a need to retrain the model to new data.

CONCLUSIONS: The presented model requires only the octanol-water partitioning ratio to predict BCFs to a fidelity consistent with existing QSAR models. This success begs re-evaluation of the modeling assumptions; specifically, it suggests that chemical uptake into arterial blood may be limited by transport across gill membranes (diffusion) rather than by counter-current flow between gill lamellae (convection). Therefore, more detailed molecular modeling of aquatic respiration may further improve predictive accuracy of the rTK approach.}, } @article {pmid30086723, year = {2018}, author = {Ribicic, D and McFarlin, KM and Netzer, R and Brakstad, OG and Winkler, A and Throne-Holst, M and Størseth, TR}, title = {Oil type and temperature dependent biodegradation dynamics - Combining chemical and microbial community data through multivariate analysis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {83}, pmid = {30086723}, issn = {1471-2180}, abstract = {BACKGROUND: This study investigates a comparative multivariate approach for studying the biodegradation of chemically dispersed oil. The rationale for this approach lies in the inherent complexity of the data and challenges associated with comparing multiple experiments with inconsistent sampling points, with respect to inferring correlations and visualizing multiple datasets with numerous variables. We aim to identify novel correlations among microbial community composition, the chemical change of individual petroleum hydrocarbons, oil type and temperature by creating modelled datasets from inconsistent sampling time points. Four different incubation experiments were conducted with freshly collected Norwegian seawater and either Grane and Troll oil dispersed with Corexit 9500. Incubations were conducted at two different temperatures (5 °C and 13 °C) over a period of 64 days.

RESULTS: PCA analysis of modelled chemical datasets and calculated half-lives revealed differences in the biodegradation of individual hydrocarbons among temperatures and oil types. At 5 °C, most n-alkanes biodegraded faster in heavy Grane oil compared to light Troll oil. PCA analysis of modelled microbial community datasets reveal differences between temperature and oil type, especially at low temperature. For both oils, Colwelliaceae and Oceanospirillaceae were more prominent in the colder incubation (5 °C) than the warmer (13 °C). Overall, Colwelliaceae, Oceanospirillaceae, Flavobacteriaceae, Rhodobacteraceae, Alteromonadaceae and Piscirickettsiaceae consistently dominated the microbial community at both temperatures and in both oil types. Other families known to include oil-degrading bacteria were also identified, such as Alcanivoracaceae, Methylophilaceae, Sphingomonadaceae and Erythrobacteraceae, but they were all present in dispersed oil incubations at a low abundance (< 1%).

CONCLUSIONS: In the current study, our goal was to introduce a comparative multivariate approach for studying the biodegradation of dispersed oil, including curve-fitted models of datasets for a greater data resolution and comparability. By applying these approaches, we have shown how different temperatures and oil types influence the biodegradation of oil in incubations with inconsistent sampling points. Clustering analysis revealed further how temperature and oil type influence single compound depletion and microbial community composition. Finally, correlation analysis of degraders community, with single compound data, revealed complexity beneath usual abundance cut-offs used for microbial community data in biodegradation studies.}, } @article {pmid30086719, year = {2018}, author = {Kasimatis, KR and Moerdyk-Schauwecker, MJ and Timmermeyer, N and Phillips, PC}, title = {Proteomic and evolutionary analyses of sperm activation identify uncharacterized genes in Caenorhabditis nematodes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {593}, pmid = {30086719}, issn = {1471-2164}, support = {T32 GM007413/GM/NIGMS NIH HHS/United States ; T32GM007413//National Institutes of Health/ ; R01GM102511//National Institutes of Health/ ; R01AG049396//National Institutes of Health/ ; }, mesh = {Animals ; Caenorhabditis/*metabolism ; Caenorhabditis elegans/metabolism ; Evolution, Molecular ; Helminth Proteins/*metabolism ; Male ; Multigene Family ; Proteomics/*methods ; Species Specificity ; Spermatozoa/*metabolism ; }, abstract = {BACKGROUND: Nematode sperm have unique and highly diverged morphology and molecular biology. In particular, nematode sperm contain subcellular vesicles known as membranous organelles that are necessary for male fertility, yet play a still unknown role in overall sperm function. Here we take a novel proteomic approach to characterize the functional protein complement of membranous organelles in two Caenorhabditis species: C. elegans and C. remanei.

RESULTS: We identify distinct protein compositions between membranous organelles and the activated sperm body. Two particularly interesting and undescribed gene families-the Nematode-Specific Peptide family, group D and the here designated Nematode-Specific Peptide family, group F-localize to the membranous organelle. Both multigene families are nematode-specific and exhibit patterns of conserved evolution specific to the Caenorhabditis clade. These data suggest gene family dynamics may be a more prevalent mode of evolution than sequence divergence within sperm. Using a CRISPR-based knock-out of the NSPF gene family, we find no evidence of a male fertility effect of these genes, despite their high protein abundance within the membranous organelles.

CONCLUSIONS: Our study identifies key components of this unique subcellular sperm component and establishes a path toward revealing their underlying role in reproduction.}, } @article {pmid30086718, year = {2018}, author = {Zhang, J and Long, Y and Wang, L and Dang, Z and Zhang, T and Song, X and Dang, Z and Pei, X}, title = {Consensus genetic linkage map construction and QTL mapping for plant height-related traits in linseed flax (Linum usitatissimum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {160}, pmid = {30086718}, issn = {1471-2229}, support = {31560401//National Natural Science Foundation of China/ ; CARS-17-GW-04//Modern Agricultural Industry Technology System/ ; ASTIP//Agricultural Science and Technology Innovation Program/ ; }, abstract = {BACKGROUND: Flax is an important field crop that can be used for either oilseed or fiber production. Plant height and technical length are important characters for flax. For linseed flax, plants usually have a short technical length and plant height than those for fiber flax. As an important agronomical character for fiber and linseed flax, plant height is usually a selection target for breeding. However, because of limited technologies and methods available, there has been little research focused on discovering the molecular mechanism controlling plant height.

RESULTS: In this study, two related recombinant inbred line (RIL) populations developed from crosses of linseed and fiber parents were developed and phenotyped for plant height and technical length in four environments. A consensus linkage map based on two RIL populations was constructed using SNP markers generated by genotyping by sequencing (GBS) technology. A total of 4497 single nucleotide polymorphism (SNP) markers were included on 15 linkage groups with an average marker density of one marker every 2.71 cM. Quantitative trait locus (QTL) mapping analysis was performed for plant height and technical length using the two populations. A total of 19 QTLs were identified for plant height and technical length. For the MH population, eight plant height QTLs and seven technical length QTLs were identified, five of which were common QTLs for both traits. For the PH population, six plant height and three technical length QTLs were identified. By comparing the QTLs and candidate gene information in the two population, two common QTLs and three candidate genes were discovered.

CONCLUSIONS: This study provides a foundation for map-based cloning of QTLs and marker-assisted selection for plant height-related traits in linseed and fiber flax.}, } @article {pmid30086717, year = {2018}, author = {Bush, SJ and Freem, L and MacCallum, AJ and O'Dell, J and Wu, C and Afrasiabi, C and Psifidi, A and Stevens, MP and Smith, J and Summers, KM and Hume, DA}, title = {Combination of novel and public RNA-seq datasets to generate an mRNA expression atlas for the domestic chicken.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {594}, pmid = {30086717}, issn = {1471-2164}, support = {BB/M011925/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/D/20211550//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/D/20211552//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J006815/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004243/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; R8/H10/56//Natural Environment Research Council (GB)/ ; MR/K001744/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Atlases as Topic ; Chickens/*genetics ; Databases, Genetic ; Gene Expression Profiling/*methods ; High-Throughput Nucleotide Sequencing ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: The domestic chicken (Gallus gallus) is widely used as a model in developmental biology and is also an important livestock species. We describe a novel approach to data integration to generate an mRNA expression atlas for the chicken spanning major tissue types and developmental stages, using a diverse range of publicly-archived RNA-seq datasets and new data derived from immune cells and tissues.

RESULTS: Randomly down-sampling RNA-seq datasets to a common depth and quantifying expression against a reference transcriptome using the mRNA quantitation tool Kallisto ensured that disparate datasets explored comparable transcriptomic space. The network analysis tool Graphia was used to extract clusters of co-expressed genes from the resulting expression atlas, many of which were tissue or cell-type restricted, contained transcription factors that have previously been implicated in their regulation, or were otherwise associated with biological processes, such as the cell cycle. The atlas provides a resource for the functional annotation of genes that currently have only a locus ID. We cross-referenced the RNA-seq atlas to a publicly available embryonic Cap Analysis of Gene Expression (CAGE) dataset to infer the developmental time course of organ systems, and to identify a signature of the expansion of tissue macrophage populations during development.

CONCLUSION: Expression profiles obtained from public RNA-seq datasets - despite being generated by different laboratories using different methodologies - can be made comparable to each other. This meta-analytic approach to RNA-seq can be extended with new datasets from novel tissues, and is applicable to any species.}, } @article {pmid30086715, year = {2018}, author = {Khoshdeli, M and Winkelmaier, G and Parvin, B}, title = {Fusion of encoder-decoder deep networks improves delineation of multiple nuclear phenotypes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {294}, pmid = {30086715}, issn = {1471-2105}, support = {R01 CA140663/CA/NCI NIH HHS/United States ; RO1CA140663//Foundation for the National Institutes of Health/ ; }, abstract = {BACKGROUND: Nuclear segmentation is an important step for profiling aberrant regions of histology sections. If nuclear segmentation can be resolved, then new biomarkers of nuclear phenotypes and their organization can be predicted for the application of precision medicine. However, segmentation is a complex problem as a result of variations in nuclear geometry (e.g., size, shape), nuclear type (e.g., epithelial, fibroblast), nuclear phenotypes (e.g., vesicular, aneuploidy), and overlapping nuclei. The problem is further complicated as a result of variations in sample preparation (e.g., fixation, staining). Our hypothesis is that (i) deep learning techniques can learn complex phenotypic signatures that rise in tumor sections, and (ii) fusion of different representations (e.g., regions, boundaries) contributes to improved nuclear segmentation.

RESULTS: We have demonstrated that training of deep encoder-decoder convolutional networks overcomes complexities associated with multiple nuclear phenotypes, where we evaluate alternative architecture of deep learning for an improved performance against the simplicity of the design. In addition, improved nuclear segmentation is achieved by color decomposition and combining region- and boundary-based features through a fusion network. The trained models have been evaluated against approximately 19,000 manually annotated nuclei, and object-level Precision, Recall, F1-score and Standard Error are reported with the best F1-score being 0.91. Raw training images, annotated images, processed images, and source codes are released as a part of the Additional file 1.

CONCLUSIONS: There are two intrinsic barriers in nuclear segmentation to H&E stained images, which correspond to the diversity of nuclear phenotypes and perceptual boundaries between adjacent cells. We demonstrate that (i) the encoder-decoder architecture can learn complex phenotypes that include the vesicular type; (ii) delineation of overlapping nuclei is enhanced by fusion of region- and edge-based networks; (iii) fusion of ENets produces an improved result over the fusion of UNets; and (iv) fusion of networks is better than multitask learning. We suggest that our protocol enables processing a large cohort of whole slide images for applications in precision medicine.}, } @article {pmid30086712, year = {2018}, author = {Nichols, AEC and Settlage, RE and Werre, SR and Dahlgren, LA}, title = {Novel roles for scleraxis in regulating adult tenocyte function.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {14}, pmid = {30086712}, issn = {1471-2121}, mesh = {Aging/*metabolism ; Animals ; Base Composition/genetics ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Cell Movement ; Cell Nucleus Shape ; Cytoskeleton/metabolism ; Down-Regulation/genetics ; Focal Adhesions/metabolism ; Gene Expression Profiling ; Gene Knockdown Techniques ; Gene Ontology ; Horses ; RNA, Messenger/genetics/metabolism ; RNA, Small Interfering/metabolism ; Reproducibility of Results ; Sequence Analysis, RNA ; Tendons/cytology ; Tenocytes/*metabolism ; }, abstract = {BACKGROUND: Tendinopathies are common and difficult to resolve due to the formation of scar tissue that reduces the mechanical integrity of the tissue, leading to frequent reinjury. Tenocytes respond to both excessive loading and unloading by producing pro-inflammatory mediators, suggesting that these cells are actively involved in the development of tendon degeneration. The transcription factor scleraxis (Scx) is required for the development of force-transmitting tendon during development and for mechanically stimulated tenogenesis of stem cells, but its function in adult tenocytes is less well-defined. The aim of this study was to further define the role of Scx in mediating the adult tenocyte mechanoresponse.

RESULTS: Equine tenocytes exposed to siRNA targeting Scx or a control siRNA were maintained under cyclic mechanical strain before being submitted for RNA-seq analysis. Focal adhesions and extracellular matrix-receptor interaction were among the top gene networks downregulated in Scx knockdown tenocytes. Correspondingly, tenocytes exposed to Scx siRNA were significantly softer, with longer vinculin-containing focal adhesions, and an impaired ability to migrate on soft surfaces. Other pathways affected by Scx knockdown included increased oxidative phosphorylation and diseases caused by endoplasmic reticular stress, pointing to a larger role for Scx in maintaining tenocyte homeostasis.

CONCLUSIONS: Our study identifies several novel roles for Scx in adult tenocytes, which suggest that Scx facilitates mechanosensing by regulating the expression of several mechanosensitive focal adhesion proteins. Furthermore, we identified a number of other pathways and targets affected by Scx knockdown that have the potential to elucidate the role that tenocytes may play in the development of degenerative tendinopathy.}, } @article {pmid30086710, year = {2018}, author = {Blighe, K and DeDionisio, L and Christie, KA and Chawes, B and Shareef, S and Kakouli-Duarte, T and Chao-Shern, C and Harding, V and Kelly, RS and Castellano, L and Stebbing, J and Lasky-Su, JA and Nesbit, MA and Moore, CBT}, title = {Gene editing in the context of an increasingly complex genome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {595}, pmid = {30086710}, issn = {1471-2164}, mesh = {Gene Editing/*methods ; Genetic Engineering ; Genetic Variation ; *Genome, Human ; Humans ; RNA, Guide/genetics ; }, abstract = {The reporting of the first draft of the human genome in 2000 brought with it much hope for the future in what was felt as a paradigm shift toward improved health outcomes. Indeed, we have now mapped the majority of variation across human populations with landmark projects such as 1000 Genomes; in cancer, we have catalogued mutations across the primary carcinomas; whilst, for other diseases, we have identified the genetic variants with strongest association. Despite this, we are still awaiting the genetic revolution in healthcare to materialise and translate itself into the health benefits for which we had hoped. A major problem we face relates to our underestimation of the complexity of the genome, and that of biological mechanisms, generally. Fixation on DNA sequence alone and a 'rigid' mode of thinking about the genome has meant that the folding and structure of the DNA molecule -and how these relate to regulation- have been underappreciated. Projects like ENCODE have additionally taught us that regulation at the level of RNA is just as important as that at the spatiotemporal level of chromatin.In this review, we chart the course of the major advances in the biomedical sciences in the era pre- and post the release of the first draft sequence of the human genome, taking a focus on technology and how its development has influenced these. We additionally focus on gene editing via CRISPR/Cas9 as a key technique, in particular its use in the context of complex biological mechanisms. Our aim is to shift the mode of thinking about the genome to that which encompasses a greater appreciation of the folding of the DNA molecule, DNA- RNA/protein interactions, and how these regulate expression and elaborate disease mechanisms.Through the composition of our work, we recognise that technological improvement is conducive to a greater understanding of biological processes and life within the cell. We believe we now have the technology at our disposal that permits a better understanding of disease mechanisms, achievable through integrative data analyses. Finally, only with greater understanding of disease mechanisms can techniques such as gene editing be faithfully conducted.}, } @article {pmid30086708, year = {2018}, author = {Llorens, C and Arcos, SC and Robertson, L and Ramos, R and Futami, R and Soriano, B and Ciordia, S and Careche, M and González-Muñoz, M and Jiménez-Ruiz, Y and Carballeda-Sangiao, N and Moneo, I and Albar, JP and Blaxter, M and Navas, A}, title = {Functional insights into the infective larval stage of Anisakis simplex s.s., Anisakis pegreffii and their hybrids based on gene expression patterns.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {592}, pmid = {30086708}, issn = {1471-2164}, support = {AGL2009-2485-C03-02//Ministerio de Economía, Industria y Competitividad, Gobierno de España/ ; FP7-312068//European Union/ ; }, mesh = {Allergens/genetics ; Animals ; Anisakis/*genetics/isolation & purification/pathogenicity ; Breeding ; Energy Metabolism ; Fish Diseases/parasitology ; Gadiformes/*parasitology ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; Helminth Proteins/*genetics ; Larva/genetics/pathogenicity ; Molecular Sequence Annotation ; Sequence Analysis, RNA/methods ; Virulence Factors/genetics ; }, abstract = {BACKGROUND: Anisakis simplex sensu stricto and Anisakis pegreffii are sibling species of nematodes parasitic on marine mammals. Zoonotic human infection with third stage infective larvae causes anisakiasis, a debilitating and potentially fatal disease. These 2 species show evidence of hybridisation in geographical areas where they are sympatric. How the species and their hybrids differ is still poorly understood.

RESULTS: Third stage larvae of Anisakis simplex s.s., Anisakis pegreffii and hybrids were sampled from Merluccius merluccius (Teleosti) hosts captured in waters of the FAO 27 geographical area. Specimens of each species and hybrids were distinguished with a diagnostic genetic marker (ITS). RNA was extracted from pools of 10 individuals of each taxon. Transcriptomes were generated using Illumina RNA-Seq, and assembled de novo. A joint assembly (here called merged transcriptome) of all 3 samples was also generated. The inferred transcript sets were functionally annotated and compared globally and also on subsets of secreted proteins and putative allergen families. While intermediary metabolism appeared to be typical for nematodes in the 3 evaluated taxa, their transcriptomes present strong levels of differential expression and enrichment, mainly of transcripts related to metabolic pathways and gene ontologies associated to energy metabolism and other pathways, with significant presence of excreted/secreted proteins, most of them allergens. The allergome of the 2 species and their hybrids has also been thoroughly studied; at least 74 different allergen families were identified in the transcriptomes.

CONCLUSIONS: A. simplex s.s., A. pegreffi and their hybrids differ in gene expression patterns in the L3 stage. Strong parent-of-origin effects were observed: A. pegreffi alleles dominate in the expression patterns of hybrids albeit the latter, and A. pegreffii also display significant differences indicating that hybrids are intermediate biological entities among their parental species, and thus of outstanding interest in the study of speciation in nematodes. Analyses of differential expression based on genes coding for secreted proteins suggests that co-infections presents different repertoires of released protein to the host environment. Both species and their hybrids, share more allergen genes than previously thought and are likely to induce overlapping disease responses.}, } @article {pmid30086702, year = {2018}, author = {Daca-Roszak, P and Swierniak, M and Jaksik, R and Tyszkiewicz, T and Oczko-Wojciechowska, M and Zebracka-Gala, J and Jarzab, B and Witt, M and Zietkiewicz, E}, title = {Transcriptomic population markers for human population discrimination.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {54}, pmid = {30086702}, issn = {1471-2156}, support = {OR00 0027 12//The National Centre for Research and Development/ ; }, abstract = {BACKGROUND: Numerous studies have demonstrated significant differences in the expression level across continental human populations. Most of published results were performed on B-cell lines materials examined under specific laboratory conditions, without further validation in a primary biological material. The goal of our study was to identify mRNA markers characterized by a significant and stable difference in the gene expression profile in Caucasian and Chinese populations, both in the commercially available B-lymphocyte cell lines and in the primary samples of the peripheral blood.

RESULTS: The preliminary selection of population-differentiating transcripts was based on Illumina expression microarray analysis of the representative group of ethnically-specified B-lymphocyte cell lines. Twenty genes with the inter-population difference in the mean expression characterized by the at least 1.5-fold change and FDR < 0.05 were identified. Subsequently, a two-step validation procedure was carried out. In the first step, a subset of selected population- differentiating transcripts was tested in the independent set of B-lymphocyte cell lines, using TLDA cards. Based on TLDA analysis, three transcripts representing Fch > 2 were chosen for validation. The differentiating status was confirmed for all of them: UTS2, UGT2B17 and SLC7A7. The mean expression of UTS2 was higher in CHB (25.8-fold change compared to CEU), while the expression of UGT2B17 and SLC7A7 was higher in CEU (3.2- and 2.2-fold change, respectively). In the next validation step, two transcripts were verified in the primary biological material. As an ultimate result of our study, two mRNA markers (UTS2 and UGT2B17) exhibiting population differences in the expression level in both B-cell line and in the blood were identified. Further statistical analysis confirmed the discriminatory potential of these two markers.

CONCLUSIONS: An inter-population differences on the level of gene expression were identified in both B-cell lines and peripheral blood samples. These findings may have a practical application in the field of forensic science. In particular, these transcripts, targeted by specific probes, may be used as population-specific targets in the efforts aiming to separate mixture of blood from individuals of different populations. Notwithstanding, these results have to be confirmed on extended population group.}, } @article {pmid30086701, year = {2018}, author = {Skoracka, A and Lopes, LF and Alves, MJ and Miller, A and Lewandowski, M and Szydło, W and Majer, A and Różańska, E and Kuczyński, L}, title = {Genetics of lineage diversification and the evolution of host usage in the economically important wheat curl mite, Aceria tosichella Keifer, 1969.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {122}, pmid = {30086701}, issn = {1471-2148}, support = {No. 01/KNOW2/2014//Funding for open access charge: Ministry of Science and Higher Education of the Republic of Poland, from the quality promoting subsidy, under the Leading National Research Centre (KNOW) program for the years 2014-2019/International ; 2011/03/B/NZ8/00129//Narodowe Centrum Nauki/International ; 2011/01/N/NZ8/04540//Narodowe Centrum Nauki/International ; UID/BIA/00329/2013//Fundação para a Ciência e a Tecnologia/International ; UID/BIA/00329/2013//Fundação para a Ciência e a Tecnologia/International ; }, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Calibration ; DNA, Mitochondrial/genetics ; Demography ; Gene Flow ; Genetic Variation ; Host-Pathogen Interactions/*genetics ; Mites/*classification/*genetics ; Mitochondria/genetics ; *Phylogeny ; Plant Diseases/*parasitology ; Time Factors ; Triticum/*parasitology ; }, abstract = {BACKGROUND: Understanding the mechanisms that underlie the diversification of herbivores through interactions with their hosts is important for their diversity assessment and identification of expansion events, particularly in a human-altered world where evolutionary processes can be exacerbated. We studied patterns of host usage and genetic structure in the wheat curl mite complex (WCM), Aceria tosichella, a major pest of the world's grain industry, to identify the factors behind its extensive diversification.

RESULTS: We expanded on previous phylogenetic research, demonstrating deep lineage diversification within the taxon, a complex of distinctive host specialist and generalist lineages more diverse than previously assumed. Time-calibrated phylogenetic reconstruction inferred from mitochondrial DNA sequence data suggests that lineage diversification pre-dates the influence of agricultural practices, and lineages started to radiate in the mid Miocene when major radiations of C4 grasses is known to have occurred. Furthermore, we demonstrated that host specificity is not phylogenetically constrained, while host generalization appears to be a more derived trait coinciding with the expansion of the world's grasslands. Demographic history of specialist lineages have been more stable when compared to generalists, and their expansion pre-dated all generalist lineages. The lack of host-associated genetic structure of generalists indicates gene flow between mite populations from different hosts.

CONCLUSIONS: Our analyses demonstrated that WCM is an unexpectedly diverse complex of genetic lineages and its differentiation is likely associated with the time of diversification and expansion of its hosts. Signatures of demographic histories and expansion of generalists are consistent with the observed proliferation of the globally most common lineages. The apparent lack of constrains on host use, coupled with a high colonization potential, hinders mite management, which may be further compromised by host range expansion. This study provides a significant contribution to the growing literature on host-association and diversification in herbivorous invertebrates.}, } @article {pmid30086548, year = {2018}, author = {De Lorenzi, L and Arrighi, S and Groppetti, D and Bonacina, S and Parma, P}, title = {Persistent Müllerian Duct Syndrome in a German Shepherd Dog.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000492037}, pmid = {30086548}, issn = {1661-5433}, abstract = {In mammals, the regression of the müllerian ducts is regulated by the action of the AMH hormone which is produced by testes during embryonic development. The action of this hormone is mediated by the only known receptor AMHR2. Mutations occurring in the AHM hormone and/or in the AMHR2 receptor gene cause the lack of regression of müllerian ducts, which may therefore persist even in male embryos carrying a XY chromosomal arrangement. This is known as the persistent müllerian duct syndrome (PMDS). A female German Shepherd dog was referred to the veterinary clinic because of urinary incontinence. She also showed an anatomical structure that protruded from and enlarged the vulvar labia. From the morphological appearance, one gonad resembled an ovary and the other a testicle. The histological examination instead showed that the gonads were both testes with an underdeveloped parenchyma and without signs of spermatogenetic activity. No alterations were found with regard to the uterus which showed a correctly developed body, cervix, and horns. Genetic analysis, performed on DNA extracted from blood, showed (i) the presence of both X and Y chromosomes, (ii) the absence of chromosome XX/XY chimerism, (iii) a normal SRY gene coding sequence, (iv) a normal AMHR2 gene coding sequence, and (v) a normal AMH gene coding sequence. In this study, we report and characterize a new case of PMDS in a dog excluding that the only mutation hitherto found in the AMHR2 gene is responsible for the observed phenotype.}, } @article {pmid30086431, year = {2018}, author = {Korpela, K and de Vos, WM}, title = {Early life colonization of the human gut: microbes matter everywhere.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {70-78}, doi = {10.1016/j.mib.2018.06.003}, pmid = {30086431}, issn = {1879-0364}, abstract = {Microbes colonising the infant intestine, especially bacteria, are considered important for metabolic and immunological programming in early life, potentially affecting the susceptibility of the host to disease. We combined published data to provide a global view of microbiota development in early life. The results support the concept that the microbiota develops with age in an orchestrated manner, showing common patterns across populations. Furthermore, infants are colonised at birth by specific, selected maternal faecal bacteria and likely their bacteriophages. Therefore, infants are adapted to receiving specific bacterial signals, partly derived from the maternal microbiota, at successive immunological time windows during early development. Birth by caesarean section compromises the initial vertical transmission of microbes whereas antibiotic use shifts the microbiota away from the normal developmental pattern. These disruptions alter the microbial signals that the host receives, potentially affecting child development.}, } @article {pmid30085387, year = {2018}, author = {Waller, BM and Kaminski, J and Setchell, JM}, title = {Primate Society of Great Britain Spring Meeting 2018: Cognition and communication.}, journal = {Evolutionary anthropology}, volume = {27}, number = {4}, pages = {140-141}, doi = {10.1002/evan.21595}, pmid = {30085387}, issn = {1520-6505}, } @article {pmid30085303, year = {2018}, author = {Otwinowski, J}, title = {Biophysical Inference of Epistasis and the Effects of Mutations on Protein Stability and Function.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2345-2354}, pmid = {30085303}, issn = {1537-1719}, support = {T32 AI055400/AI/NIAID NIH HHS/United States ; }, abstract = {Understanding the relationship between protein sequence, function, and stability is a fundamental problem in biology. The essential function of many proteins that fold into a specific structure is their ability to bind to a ligand, which can be assayed for thousands of mutated variants. However, binding assays do not distinguish whether mutations affect the stability of the binding interface or the overall fold. Here, we introduce a statistical method to infer a detailed energy landscape of how a protein folds and binds to a ligand by combining information from many mutated variants. We fit a thermodynamic model describing the bound, unbound, and unfolded states to high quality data of protein G domain B1 binding to IgG-Fc. We infer distinct folding and binding energies for each mutation providing a detailed view of how mutations affect binding and stability across the protein. We accurately infer the folding energy of each variant in physical units, validated by independent data, whereas previous high-throughput methods could only measure indirect changes in stability. While we assume an additive sequence-energy relationship, the binding fraction is epistatic due its nonlinear relation to energy. Despite having no epistasis in energy, our model explains much of the observed epistasis in binding fraction, with the remaining epistasis identifying conformationally dynamic regions.}, } @article {pmid30085185, year = {2018}, author = {Hockenberry, AJ and Jewett, MC and Amaral, LAN and Wilke, CO}, title = {Within-Gene Shine-Dalgarno Sequences Are Not Selected for Function.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2487-2498}, pmid = {30085185}, issn = {1537-1719}, support = {R01 GM088344/GM/NIGMS NIH HHS/United States ; }, abstract = {The Shine-Dalgarno (SD) sequence motif facilitates translation initiation and is frequently found upstream of bacterial start codons. However, thousands of instances of this motif occur throughout the middle of protein coding genes in a typical bacterial genome. Here, we use comparative evolutionary analysis to test whether SD sequences located within genes are functionally constrained. We measure the conservation of SD sequences across Enterobacteriales, and find that they are significantly less conserved than expected. Further, the strongest SD sequences are the least conserved whereas we find evidence of conservation for the weakest possible SD sequences given amino acid constraints. Our findings indicate that most SD sequences within genes are likely to be deleterious and removed via selection. To illustrate the origin of these deleterious costs, we show that ATG start codons are significantly depleted downstream of SD sequences within genes, highlighting the constraint that these sequences impose on the surrounding nucleotides to minimize the potential for erroneous translation initiation.}, } @article {pmid30085180, year = {2018}, author = {Bolívar, P and Mugal, CF and Rossi, M and Nater, A and Wang, M and Dutoit, L and Ellegren, H}, title = {Biased Inference of Selection Due to GC-Biased Gene Conversion and the Rate of Protein Evolution in Flycatchers When Accounting for It.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2475-2486}, pmid = {30085180}, issn = {1537-1719}, abstract = {The rate of recombination impacts on rates of protein evolution for at least two reasons: it affects the efficacy of selection due to linkage and influences sequence evolution through the process of GC-biased gene conversion (gBGC). We studied how recombination, via gBGC, affects inferences of selection in gene sequences using comparative genomic and population genomic data from the collared flycatcher (Ficedula albicollis). We separately analyzed different mutation categories ("strong"-to-"weak," "weak-to-strong," and GC-conservative changes) and found that gBGC impacts on the distribution of fitness effects of new mutations, and leads to that the rate of adaptive evolution and the proportion of adaptive mutations among nonsynonymous substitutions are underestimated by 22-33%. It also biases inferences of demographic history based on the site frequency spectrum. In light of this impact, we suggest that inferences of selection (and demography) in lineages with pronounced gBGC should be based on GC-conservative changes only. Doing so, we estimate that 10% of nonsynonymous mutations are effectively neutral and that 27% of nonsynonymous substitutions have been fixed by positive selection in the flycatcher lineage. We also find that gene expression level, sex-bias in expression, and the number of protein-protein interactions, but not Hill-Robertson interference (HRI), are strong determinants of selective constraint and rate of adaptation of collared flycatcher genes. This study therefore illustrates the importance of disentangling the effects of different evolutionary forces and genetic factors in interpretation of sequence data, and from that infer the role of natural selection in DNA sequence evolution.}, } @article {pmid30085124, year = {2018}, author = {Grosche, C and Diehl, A and Rensing, SA and Maier, UG}, title = {Iron-Sulfur Cluster Biosynthesis in Algae with Complex Plastids.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2061-2071}, pmid = {30085124}, issn = {1759-6653}, mesh = {Cell Compartmentation ; Cryptophyta/genetics/*metabolism ; Cytosol/metabolism ; Diatoms/genetics ; Genome ; Iron-Sulfur Proteins/*biosynthesis ; Models, Biological ; Phylogeny ; Plastids/*metabolism ; }, abstract = {Plastids surrounded by four membranes harbor a special compartment between the outer and inner plastid membrane pair, the so-called periplastidal compartment (PPC). This cellular structure is usually presumed to be the reduced cytoplasm of a eukaryotic phototrophic endosymbiont, which was integrated into a host cell and streamlined into a plastid with a complex membrane structure. Up to date, no mitochondrion or mitochondrion-related organelle has been identified in the PPC of any representative. However, two prominent groups, the cryptophytes and the chlorarachniophytes, still harbor a reduced cell nucleus of symbiont origin, the nucleomorph, in their PPCs. Generally, many cytoplasmic and nucleus-located eukaryotic proteins need an iron-sulfur cofactor for their functionality. Beside some exceptions, their synthesis is depending on a so-called iron-sulfur complex (ISC) assembly machinery located in the mitochondrion. This machinery provides the cytoplasm with a still unknown sulfur component, which is then converted into iron-sulfur clusters via a cytosolic iron-sulfur protein assembly (CIA) machinery. Here, we investigated if a CIA machinery is present in mitochondrion-lacking PPCs. By using bioinformatic screens and in vivo-localizations of candidate proteins, we show that the presence of a PPC-specific CIA machinery correlates with the presence of a nucleomorph. Phylogenetic analyses of PPC- and host specific CIA components additionally indicate a complex evolution of the CIA machineries in organisms having plastids surrounded by four membranes.}, } @article {pmid30085110, year = {2018}, author = {Shao, GM and Li, XY and Wang, Y and Wang, ZW and Li, Z and Zhang, XJ and Zhou, L and Gui, JF}, title = {Whole Genome Incorporation and Epigenetic Stability in a Newly Synthetic Allopolyploid of Gynogenetic Gibel Carp.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2394-2407}, pmid = {30085110}, issn = {1759-6653}, abstract = {Allopolyploidization plays an important role in speciation, and some natural or synthetic allopolyploid fishes have been extensively applied to aquaculture. Although genetic and epigenetic inheritance and variation associated with plant allopolyploids have been well documented, the relative research in allopolyploid animals is scarce. In this study, the genome constitution and DNA methylation inheritance in a newly synthetic allopolyploid of gynogenetic gibel carp were analyzed. The incorporation of a whole genome of paternal common carp sperm in the allopolyploid was confirmed by genomic in situ hybridization, chromosome localization of 45S rDNAs, and sequence comparison. Pooled sample-based methylation sensitive amplified polymorphism (MSAP) revealed that an overwhelming majority (98.82%) of cytosine methylation patterns in the allopolyploid were inherited from its parents of hexaploid gibel carp clone D and common carp. Compared to its parents, 11 DNA fragments in the allopolyploid were proved to be caused by interindividual variation, recombination, deletion, and mutation through individual sample-based MSAP and sequencing. Contrast to the rapid and remarkable epigenetic changes in most of analyzed neopolyploids, no cytosine methylation variation was detected in the gynogenetic allopolyploid. Therefore, the newly synthetic allopolyploid of gynogenetic gibel carp combined genomes from its parents and maintained genetic and epigenetic stability after its formation and subsequently seven successive gynogenetic generations. Our current results provide a paradigm for recurrent polyploidy consequences in the gynogenetic allopolyploid animals.}, } @article {pmid30085090, year = {2018}, author = {Röttjers, L and Faust, K}, title = {From hairballs to hypotheses-biological insights from microbial networks.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {6}, pages = {761-780}, pmid = {30085090}, issn = {1574-6976}, mesh = {Computer Simulation ; Environment ; Microbiota/*physiology ; Models, Biological ; }, abstract = {Microbial networks are an increasingly popular tool to investigate microbial community structure, as they integrate multiple types of information and may represent systems-level behaviour. Interpreting these networks is not straightforward, and the biological implications of network properties are unclear. Analysis of microbial networks allows researchers to predict hub species and species interactions. Additionally, such analyses can help identify alternative community states and niches. Here, we review factors that can result in spurious predictions and address emergent properties that may be meaningful in the context of the microbiome. We also give an overview of studies that analyse microbial networks to identify new hypotheses. Moreover, we show in a simulation how network properties are affected by tool choice and environmental factors. For example, hub species are not consistent across tools, and environmental heterogeneity induces modularity. We highlight the need for robust microbial network inference and suggest strategies to infer networks more reliably.}, } @article {pmid30085063, year = {2018}, author = {Buckner, MMC and Ciusa, ML and Piddock, LJV}, title = {Strategies to combat antimicrobial resistance: anti-plasmid and plasmid curing.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {6}, pages = {781-804}, pmid = {30085063}, issn = {1574-6976}, support = {//Wellcome Trust/United Kingdom ; MR/N012933/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/genetics ; Drug Resistance, Bacterial/*genetics ; Environmental Microbiology ; Gene Transfer, Horizontal ; Genes, Bacterial/*genetics ; Humans ; Plasmids/*genetics ; }, abstract = {Antimicrobial resistance (AMR) is a global problem hindering treatment of bacterial infections, rendering many aspects of modern medicine less effective. AMR genes (ARGs) are frequently located on plasmids, which are self-replicating elements of DNA. They are often transmissible between bacteria, and some have spread globally. Novel strategies to combat AMR are needed, and plasmid curing and anti-plasmid approaches could reduce ARG prevalence, and sensitise bacteria to antibiotics. We discuss the use of curing agents as laboratory tools including chemicals (e.g. detergents and intercalating agents), drugs used in medicine including ascorbic acid, psychotropic drugs (e.g. chlorpromazine), antibiotics (e.g. aminocoumarins, quinolones and rifampicin) and plant-derived compounds. Novel strategies are examined; these include conjugation inhibitors (e.g. TraE inhibitors, linoleic, oleic, 2-hexadecynoic and tanzawaic acids), systems designed around plasmid incompatibility, phages and CRISPR/Cas-based approaches. Currently, there is a general lack of in vivo curing options. This review highlights this important shortfall, which if filled could provide a promising mechanism to reduce ARG prevalence in humans and animals. Plasmid curing mechanisms which are not suitable for in vivo use could still prove important for reducing the global burden of AMR, as high levels of ARGs exist in the environment.}, } @article {pmid30085042, year = {2018}, author = {Acedo, JZ and Chiorean, S and Vederas, JC and van Belkum, MJ}, title = {The expanding structural variety among bacteriocins from Gram-positive bacteria.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {6}, pages = {805-828}, doi = {10.1093/femsre/fuy033}, pmid = {30085042}, issn = {1574-6976}, mesh = {Bacteriocins/*chemistry/*metabolism ; Gram-Positive Bacteria/chemistry/*physiology ; }, abstract = {Bacteria use various strategies to compete in an ecological niche, including the production of bacteriocins. Bacteriocins are ribosomally synthesized antibacterial peptides, and it has been postulated that the majority of Gram-positive bacteria produce one or more of these natural products. Bacteriocins can be used in food preservation and are also considered as potential alternatives to antibiotics. The majority of bacteriocins from Gram-positive bacteria had been traditionally divided into two major classes, namely lantibiotics, which are post-translationally modified bacteriocins, and unmodified bacteriocins. The last decade has seen an expanding number of ribosomally synthesized and post-translationally modified peptides (RiPPs) in Gram-positive bacteria that have antibacterial activity. These include linear azol(in)e-containing peptides, thiopeptides, bottromycins, glycocins, lasso peptides and lipolanthines. In addition, the three-dimensional (3D) structures of a number of modified and unmodified bacteriocins have been elucidated in recent years. This review gives an overview on the structural variety of bacteriocins from Gram-positive bacteria. It will focus on the chemical and 3D structures of these peptides, and their interactions with receptors and membranes, structure-function relationships and possible modes of action.}, } @article {pmid30084997, year = {2018}, author = {Fouilland, E and Floc'h, EL and Brennan, D and Bell, EM and Lordsmith, SL and McNeill, S and Mitchell, E and Brand, TD and García-Martín, EE and Leakey, RJ}, title = {Assessment of bacterial dependence on marine primary production along a northern latitudinal gradient.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy150}, pmid = {30084997}, issn = {1574-6941}, abstract = {Recent observations in polar marine waters have shown that a large fraction of primary production may be lost to respiration by planktonic bacteria due to very low bacterial growth efficiencies in cold waters. Here we report that sea temperature may be a key factor (but not the only one) influencing the interaction between bacteria and primary production in North Atlantic and Arctic waters, suggesting that low primary production rates could not sustain bacterial carbon demand in the coldest Arctic waters. The use of freshly produced phytoplankton exudate by bacteria in early- and mid-summer was assessed, together with the bacterial uptake of dissolved inorganic nitrogen (DIN = nitrate and ammonium), in surface waters along a latitudinal gradient from the North Sea to the Arctic sea ice. Bacterial production was independent of the low primary production measured in the coldest waters. Under these conditions, heterotrophic bacteria can consume a large fraction of DIN and N-rich organic matter, making them strong contributors to N fluxes in these waters.}, } @article {pmid30084235, year = {2018}, author = {Markussen, T and Happel, EM and Teikari, JE and Huchaiah, V and Alneberg, J and Andersson, AF and Sivonen, K and Riemann, L and Middelboe, M and Kisand, V}, title = {Coupling biogeochemical process rates and metagenomic blueprints of coastal bacterial assemblages in the context of environmental change.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3083-3099}, doi = {10.1111/1462-2920.14371}, pmid = {30084235}, issn = {1462-2920}, support = {//Estonian Research Council/ ; //Academy of Finland/ ; //Swedish Research Council FORMAS/ ; //Danish Council for Independent Research/ ; }, abstract = {Bacteria are major drivers of biogeochemical nutrient cycles and energy fluxes in marine environments, yet how bacterial communities respond to environmental change is not well known. Metagenomes allow examination of genetic responses of the entire microbial community to environmental change. However, it is challenging to link metagenomes directly to biogeochemical process rates. Here, we investigate metagenomic responses in natural bacterioplankton communities to simulated environmental stressors in the Baltic Sea, including increased river water input, increased nutrient concentration, and reduced oxygen level. This allowed us to identify informative prokaryotic gene markers, responding to environmental perturbation. Our results demonstrate that metagenomic and metabolic changes in bacterial communities in response to environmental stressors are influenced both by the initial community composition and by the biogeochemical factors shaping the functional response. Furthermore, the different sources of dissolved organic matter (DOM) had the largest impact on metagenomic blueprint. Most prominently, changes in DOM loads influenced specific transporter types reflecting the substrate availability and DOC assimilation and consumption pathways. The results provide new knowledge for developing models of ecosystem structure and biogeochemical cycling in future climate change scenarios and advance our exploration of the potential use of marine microorganisms as markers for environmental conditions.}, } @article {pmid30084139, year = {2018}, author = {Sasakawa, K and Kon, Y}, title = {Learning-induced host preference in male parasitoid wasps as a potential driver of ecological speciation.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1750-1755}, doi = {10.1111/jeb.13363}, pmid = {30084139}, issn = {1420-9101}, support = {17K15171//Japan Society for the Promotion of Science/ ; 25830150//Japan Society for the Promotion of Science/ ; }, abstract = {Ecological speciation via a host shift plays an important role in the diversification of phytophagous and parasitic insects. However, it is not clear how separation is maintained among initial populations in which genetic separation mechanisms are not fully established. Learning-induced host preference in females can contribute to host fidelity and result in a barrier to gene flow in the initial populations. However, the role of males, which also affects gene flow, has been largely unexplored. We examined host preference through induced learning in males, which can contribute to initial population divergence, in the parasitoid wasp, Anisopteromalus calandrae, and two host species, Callosobruchus chinensis and C. maculatus. Behavioural experiments were performed using a four-chamber olfactometer. When wasps were conditioned during the preimaginal and early adult stage without mating experience, no preference was induced regardless of the host species. However, when wasps were conditioned at the early adult stage using the odour of the rearing host and mate reward, preference was induced in both host species. These results demonstrate mate reward learning-induced host preference in males. Interestingly, when the rearing host species and the mating conditioning host species were interchanged, preference was induced only in males conditioned to C. maculatus at mating. Thus, depending on the host species, preimaginal and early adult learning is vital to preference induction. Our results suggest that behavioural change via learning in males plays a more important role in the ecological speciation of phytophagous and parasitic insects than previously recognized.}, } @article {pmid30084095, year = {2018}, author = {Dicks, LMT and Mikkelsen, LS and Brandsborg, E and Marcotte, H}, title = {Clostridium difficile, the Difficult "Kloster" Fuelled by Antibiotics.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1543-8}, pmid = {30084095}, issn = {1432-0991}, abstract = {Clostridium difficile is normally present in low numbers in a healthy adult gastro-intestinal tract (GIT). Drastic changes in the microbial population, e.g., dysbiosis caused by extensive treatment with antibiotics, stimulates the growth of resistant strains and the onset of C. difficile infection (CDI). Symptoms of infection varies from mild diarrhea to colitis (associated with dehydration and bleeding), pseudomembranous colitis with yellow ulcerations in the mucosa of the colon, to fulminant colitis (perforation of the gut membrane), and multiple organ failure. Inflamed epithelial cells and damaged mucosal tissue predisposes the colon to other opportunistic pathogens such as Clostridium perfringens, Staphylococcus aureus, Klebsiella oxytoca, Candida spp., and Salmonella spp. This may lead to small intestinal bacterial overgrowth (SIBO), sepsis, toxic megacolon, and even colorectal cancer. Many stains of C. difficile are resistant to metronidazole and vancomycin. Vaccination may be an answer to CDI, but requires more research. Success in treatment with probiotics depends on the strains used. Oral or rectal fecal transplants are partly effective, as spores in the small intestine may germinate and colonize the colon. The effect of antibiotics on C. difficile and commensal gut microbiota is summarized and changes in gut physiology are discussed. The need to search for non-antibiotic methods in the treatment of CDI and C. difficile-associated disease (CDAD) is emphasized.}, } @article {pmid30083050, year = {2018}, author = {Yang, M and Han, N and Li, H and Meng, L}, title = {Transcriptome Analysis and Microsatellite Markers Development of a Traditional Chinese Medicinal Herb Halenia elliptica D. Don (Gentianaceae).}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318790263}, pmid = {30083050}, issn = {1176-9343}, abstract = {Halenia elliptica is a popular Chinese medicinal herb that is used to treat jaundice disease and virus hepatitis, and its wild populations have been reduced significantly due to overharvesting recently. However, effective conservation could not be implemented because of the lack of genomic information and genetic markers. In this study, a de novo transcriptome of H elliptica was sequenced using the NGS Illumina, and 132 695 unigenes with the length >200 bp (base pairs) were obtained. Among them, a total of 32 109 unigenes were scanned to develop simple sequence repeats (SSRs). Based on NCBI (National Center for Biotechnology Information) nonredundant database (Nr), these SSR sequences were annotated and assigned into gene ontology categories. In addition, we designed 126 pairs of SSR primers for polymerase chain reaction amplification, of which 12 pairs were identified to be polymorphic among 40 individuals from 8 populations. We then used the 12 polymorphic SSRs to construct a UPGMA dendrogram of the 40 individuals. In addition, a significant correlation between the genetic relationship and the geographic distance was found, suggesting a phylogeographic structure in H elliptica. Moreover, 2 of these SSRs were also successfully amplified in a related species Veratrilla baillonii, suggesting their cross-species transferability. Generally, the SSR markers with high polymorphisms identified in this study provide valuable genetic resources and represent an initial step for exploring the genetic diversity and population histories of H elliptica and its related species.}, } @article {pmid30083049, year = {2018}, author = {Yar, AM and Zaman, G and Hussain, A and Changhui, Y and Rasul, A and Hussain, A and Bo, Z and Bokhari, H and Ibrahim, M}, title = {Comparative Genome Analysis of 2 Mycobacterium Tuberculosis Strains from Pakistan: Insights Globally Into Drug Resistance, Virulence, and Niche Adaptation.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318790252}, pmid = {30083049}, issn = {1176-9343}, abstract = {Multidrug-resistant Mycobacterium tuberculosis is a global threat particularly in developing countries like Pakistan. In this study, we identified 2 M tuberculosis strains, mnpk and swlpk, by 16S RNA genes, sequenced their draft genome, and compared the 2 genomes with reference strain H37Rv and gene expression analysis of selected virulent genes. Phylogenetic analysis of M tuberculosis strains, mnpk and swlpk, using 16S RNA genes revealed that the strains are closely related with reference strain H37Rv. The draft genome sequence of mnpk and swlpk contains 4305 and 4295 protein-coding genes, respectively, having 99.9% with high collinearity when compared with H37Rv. Although some important drug-resistant genes such as fabG, faDE24, and iniA were missing, genome mining also revealed key drug-resistant genes such as katG, inhA, rpoA, rpoB, and rpoC against first-line isoniazid and rifampicin drug. The strain mnpk and swlpk encodes 257 putative and 86 verified virulent genes including type 7 secretion system (T7SS) key genes. The variation in the expression profile of selected T7SS genes, particularly low expression level of EspK, raised concern that the mechanism of virulence of mnpk and swlpk might be different from H37Rv strains as espK is associated with ATPase EccC1a and EccC1b which showed high expression level. Briefly, this study shows that the strains mnpk and swlpk are linked with H37Rv having 99% similarity in genomes, but the absence of drug-resistant genes and variation in key genes' expression profile espK, EccE1, PPE41, and espC provide a rationale for the future investigation of M tuberculosis mnpk and swlpk pathogenesis via RNA sequencing, single-nucleotide polymorphisms, as well as gene manipulation.}, } @article {pmid30082855, year = {2018}, author = {Koch, L}, title = {Transcriptomics in intact tissues.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {593}, doi = {10.1038/s41576-018-0045-7}, pmid = {30082855}, issn = {1471-0064}, } @article {pmid30082854, year = {2018}, author = {Koch, L}, title = {Evolution of eusociality.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {592}, doi = {10.1038/s41576-018-0044-8}, pmid = {30082854}, issn = {1471-0064}, } @article {pmid30082787, year = {2018}, author = {Yang, Z and Qian, S and Scheid, RN and Lu, L and Chen, X and Liu, R and Du, X and Lv, X and Boersma, MD and Scalf, M and Smith, LM and Denu, JM and Du, J and Zhong, X}, title = {EBS is a bivalent histone reader that regulates floral phase transition in Arabidopsis.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1247-1253}, doi = {10.1038/s41588-018-0187-8}, pmid = {30082787}, issn = {1546-1718}, support = {R37 GM059785/GM/NIGMS NIH HHS/United States ; }, abstract = {The ability of cells to perceive and translate versatile cues into differential chromatin and transcriptional states is critical for many biological processes1-5. In plants, timely transition to a flowering state is crucial for successful reproduction6-9. EARLY BOLTING IN SHORT DAY (EBS) is a negative transcriptional regulator that prevents premature flowering in Arabidopsis thaliana10,11. We found that EBS contains bivalent bromo-adjacent homology (BAH)-plant homeodomain (PHD) reader modules that bind H3K27me3 and H3K4me3, respectively. We observed co-enrichment of a subset of EBS-associated genes with H3K4me3, H3K27me3, and Polycomb repressor complex 2 (PRC2). Notably, EBS adopted an autoinhibition mode to mediate its switch in binding preference between H3K27me3 and H3K4me3. This binding balance was critical because disruption of either EBS-H3K27me3 or EBS-H3K4me3 interaction induced early floral transition. Our results identify a bivalent chromatin reader capable of recognizing two antagonistic histone marks, and we propose a distinct mechanism of interaction between active and repressive chromatin states.}, } @article {pmid30082786, year = {2018}, author = {Li, Z and Fu, X and Wang, Y and Liu, R and He, Y}, title = {Polycomb-mediated gene silencing by the BAH-EMF1 complex in plants.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1254-1261}, doi = {10.1038/s41588-018-0190-0}, pmid = {30082786}, issn = {1546-1718}, abstract = {Polycomb proteins implement genome-wide transcriptional repression in multicellular organisms. The evolutionarily conserved Polycomb repressive complex 2 (PRC2) catalyzes histone H3 Lys27 trimethylation (H3K27me3) that is read and effected by Polycomb repressive complex 1 (PRC1) in animals, but the interpretation of this mark remains unclear in plants. Here we report that in the eudicot Arabidopsis thaliana two homologous BAH (Bromo adjacent homology) domain-containing proteins form a plant-specific complex with EMBRYONIC FLOWER 1 (EMF1), and that the BAH-EMF1 complex (BAH-EMF1c) reads and effects the H3K27me3 mark and mediates genome-wide transcriptional repression. Furthermore, in the monocot rice a homolog of the Arabidopsis BAH-domain proteins also binds methylated H3K27 and forms a complex with the rice homolog of EMF1, suggesting that BAH-EMF1c is conserved in flowering plants. Therefore, our results show that the plant-specific BAH-EMF1c fulfills PRC1-like functions in higher plants, suggesting a convergent evolution of PRC1 activity in plants and animals.}, } @article {pmid30082785, year = {2018}, author = {Vigneau, S and Vinogradova, S and Savova, V and Gimelbrant, A}, title = {High prevalence of clonal monoallelic expression.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1198-1199}, doi = {10.1038/s41588-018-0188-7}, pmid = {30082785}, issn = {1546-1718}, } @article {pmid30082784, year = {2018}, author = {Reinius, B and Sandberg, R}, title = {Reply to 'High prevalence of clonal monoallelic expression'.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1199-1200}, doi = {10.1038/s41588-018-0189-6}, pmid = {30082784}, issn = {1546-1718}, } @article {pmid30082739, year = {2018}, author = {Kukekova, AV and Johnson, JL and Xiang, X and Feng, S and Liu, S and Rando, HM and Kharlamova, AV and Herbeck, Y and Serdyukova, NA and Xiong, Z and Beklemischeva, V and Koepfli, KP and Gulevich, RG and Vladimirova, AV and Hekman, JP and Perelman, PL and Graphodatsky, AS and O'Brien, SJ and Wang, X and Clark, AG and Acland, GM and Trut, LN and Zhang, G}, title = {Red fox genome assembly identifies genomic regions associated with tame and aggressive behaviours.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1479-1491}, doi = {10.1038/s41559-018-0611-6}, pmid = {30082739}, issn = {2397-334X}, abstract = {Strains of red fox (Vulpes vulpes) with markedly different behavioural phenotypes have been developed in the famous long-term selective breeding programme known as the Russian farm-fox experiment. Here we sequenced and assembled the red fox genome and re-sequenced a subset of foxes from the tame, aggressive and conventional farm-bred populations to identify genomic regions associated with the response to selection for behaviour. Analysis of the re-sequenced genomes identified 103 regions with either significantly decreased heterozygosity in one of the three populations or increased divergence between the populations. A strong positional candidate gene for tame behaviour was highlighted: SorCS1, which encodes the main trafficking protein for AMPA glutamate receptors and neurexins and suggests a role for synaptic plasticity in fox domestication. Other regions identified as likely to have been under selection in foxes include genes implicated in human neurological disorders, mouse behaviour and dog domestication. The fox represents a powerful model for the genetic analysis of affiliative and aggressive behaviours that can benefit genetic studies of behaviour in dogs and other mammals, including humans.}, } @article {pmid30082738, year = {2018}, author = {Casey-Bryars, M and Reeve, R and Bastola, U and Knowles, NJ and Auty, H and Bachanek-Bankowska, K and Fowler, VL and Fyumagwa, R and Kazwala, R and Kibona, T and King, A and King, DP and Lankester, F and Ludi, AB and Lugelo, A and Maree, FF and Mshanga, D and Ndhlovu, G and Parekh, K and Paton, DJ and Perry, B and Wadsworth, J and Parida, S and Haydon, DT and Marsh, TL and Cleaveland, S and Lembo, T}, title = {Waves of endemic foot-and-mouth disease in eastern Africa suggest feasibility of proactive vaccination approaches.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1449-1457}, doi = {10.1038/s41559-018-0636-x}, pmid = {30082738}, issn = {2397-334X}, support = {BB/H009175/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Livestock production in Africa is key to national economies, food security and rural livelihoods, and > 85% of livestock keepers live in extreme poverty. With poverty elimination central to the Sustainable Development Goals, livestock keepers are therefore critically important. Foot-and-mouth disease is a highly contagious livestock disease widespread in Africa that contributes to this poverty. Despite its US$2.3 billion impact, control of the disease is not prioritized: standard vaccination regimens are too costly, its impact on the poorest is underestimated, and its epidemiology is too weakly understood. Our integrated analysis in Tanzania shows that the disease is of high concern, reduces household budgets for human health, and has major impacts on milk production and draft power for crop production. Critically, foot-and-mouth disease outbreaks in cattle are driven by livestock-related factors with a pattern of changing serotype dominance over time. Contrary to findings in southern Africa, we find no evidence of frequent infection from wildlife, with outbreaks in cattle sweeping slowly across the region through a sequence of dominant serotypes. This regularity suggests that timely identification of the epidemic serotype could allow proactive vaccination ahead of the wave of infection, mitigating impacts, and our preliminary matching work has identified potential vaccine candidates. This strategy is more realistic than wildlife-livestock separation or conventional foot-and-mouth disease vaccination approaches. Overall, we provide strong evidence for the feasibility of coordinated foot-and-mouth disease control as part of livestock development policies in eastern Africa, and our integrated socioeconomic, epidemiological, laboratory and modelling approach provides a framework for the study of other disease systems.}, } @article {pmid30082737, year = {2018}, author = {Lau, MSY and Grenfell, BT}, title = {Vaccination under uncertainty.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1350-1351}, doi = {10.1038/s41559-018-0652-x}, pmid = {30082737}, issn = {2397-334X}, } @article {pmid30082736, year = {2018}, author = {Burgarella, C and Cubry, P and Kane, NA and Varshney, RK and Mariac, C and Liu, X and Shi, C and Thudi, M and Couderc, M and Xu, X and Chitikineni, A and Scarcelli, N and Barnaud, A and Rhoné, B and Dupuy, C and François, O and Berthouly-Salazar, C and Vigouroux, Y}, title = {A western Sahara centre of domestication inferred from pearl millet genomes.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1377-1380}, doi = {10.1038/s41559-018-0643-y}, pmid = {30082736}, issn = {2397-334X}, abstract = {There have been intense debates over the geographic origin of African crops and agriculture. Here, we used whole-genome sequencing data to infer the domestication origin of pearl millet (Cenchrus americanus). Our results supported an origin in western Sahara, and we dated the onset of cultivated pearl millet expansion in Africa to 4,900 years ago. We provided evidence that wild-to-crop gene flow increased cultivated genetic diversity leading to diversity hotspots in western and eastern Sahel and adaptive introgression of 15 genomic regions. Our study reconciled genetic and archaeological data for one of the oldest African crops.}, } @article {pmid30082735, year = {2018}, author = {Grass, I and Jauker, B and Steffan-Dewenter, I and Tscharntke, T and Jauker, F}, title = {Past and potential future effects of habitat fragmentation on structure and stability of plant-pollinator and host-parasitoid networks.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1408-1417}, doi = {10.1038/s41559-018-0631-2}, pmid = {30082735}, issn = {2397-334X}, abstract = {Habitat fragmentation is a primary threat to biodiversity, but how it affects the structure and stability of ecological networks is poorly understood. Here, we studied plant-pollinator and host-parasitoid networks on 32 calcareous grassland fragments covering a size gradient of several orders of magnitude and with amounts of additional habitat availability in the surrounding landscape that varied independent of fragment size. We find that additive and interactive effects of habitat fragmentation at local (fragment size) and landscape scales (1,750 m radius) directly shape species communities by altering the number of interacting species and, indirectly, their body size composition. These, in turn, affect plant-pollinator, but not host-parasitoid, network structure: the nestedness and modularity of plant-pollinator networks increase with pollinator body size. Moreover, pollinator richness increases modularity. In contrast, the modularity of host-parasitoid networks decreases with host richness, whereas neither parasitoid richness nor body size affects network structure. Simulating species coextinctions also reveals that the structure-stability relationship depends on species' sensitivity to coextinctions and their capacity for adaptive partner switches, which differ between mutualistic and antagonistic interaction partners. While plant-pollinator communities may cope with future habitat fragmentation by responding to species loss with opportunistic partner switches, past effects of fragmentation on the current structure of host-parasitoid networks may strongly affect their robustness to coextinctions under future habitat fragmentation.}, } @article {pmid30082724, year = {2018}, author = {Hicks, ND and Yang, J and Zhang, X and Zhao, B and Grad, YH and Liu, L and Ou, X and Chang, Z and Xia, H and Zhou, Y and Wang, S and Dong, J and Sun, L and Zhu, Y and Zhao, Y and Jin, Q and Fortune, SM}, title = {Clinically prevalent mutations in Mycobacterium tuberculosis alter propionate metabolism and mediate multidrug tolerance.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1032-1042}, pmid = {30082724}, issn = {2058-5276}, support = {T32 AI007638/AI/NIAID NIH HHS/United States ; T32 AI049928/AI/NIAID NIH HHS/United States ; U19 AI109755/AI/NIAID NIH HHS/United States ; }, abstract = {The global epidemic of drug-resistant tuberculosis is a catastrophic example of how antimicrobial resistance is undermining the public health gains made possible by combination drug therapy. Recent evidence points to unappreciated bacterial factors that accelerate the emergence of drug resistance. In a genome-wide association study of Mycobacterium tuberculosis isolates from China, we find mutations in the gene encoding the transcription factor prpR enriched in drug-resistant strains. prpR mutations confer conditional drug tolerance to three of the most effective classes of antibiotics by altering propionyl-CoA metabolism. prpR-mediated drug tolerance is carbon-source dependent, and while readily detectable during infection of human macrophages, is not captured by standard susceptibility testing. These data define a previously unrecognized and clinically prevalent class of M. tuberculosis variants that undermine antibiotic efficacy and drive drug resistance.}, } @article {pmid30082697, year = {2018}, author = {}, title = {A star that hides its shine draws admiring looks.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {141}, doi = {10.1038/d41586-018-05886-4}, pmid = {30082697}, issn = {1476-4687}, } @article {pmid30082696, year = {2018}, author = {Wan, Z and Chen, J}, title = {Human errors are behind most oil-tanker spills.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {161-163}, doi = {10.1038/d41586-018-05852-0}, pmid = {30082696}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/drug effects ; China ; Disasters/*statistics & numerical data ; Ecosystem ; Oceans and Seas ; Petroleum Pollution/adverse effects/*statistics & numerical data ; Seawater/*chemistry ; *Ships ; }, } @article {pmid30082695, year = {2018}, author = {Kwok, R}, title = {How to pick an electronic laboratory notebook.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {269-270}, doi = {10.1038/d41586-018-05895-3}, pmid = {30082695}, issn = {1476-4687}, } @article {pmid30082694, year = {2018}, author = {Draaisma, D}, title = {Probing the genetics of the mind.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {166}, doi = {10.1038/d41586-018-05893-5}, pmid = {30082694}, issn = {1476-4687}, } @article {pmid30082693, year = {2018}, author = {Ball, P}, title = {Two slits and one hell of a quantum conundrum.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {165}, doi = {10.1038/d41586-018-05892-6}, pmid = {30082693}, issn = {1476-4687}, } @article {pmid30082692, year = {2018}, author = {Abedalthagafi, M}, title = {A Jordanian biologist redefines success for women in science.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {164}, doi = {10.1038/d41586-018-05891-7}, pmid = {30082692}, issn = {1476-4687}, } @article {pmid30082469, year = {2018}, author = {Sossin, WS and Costa-Mattioli, M}, title = {Translational Control in the Brain in Health and Disease.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032912}, pmid = {30082469}, issn = {1943-0264}, abstract = {Translational control in neurons is crucially required for long-lasting changes in synaptic function and memory storage. The importance of protein synthesis control to brain processes is underscored by the large number of neurological disorders in which translation rates are perturbed, such as autism and neurodegenerative disorders. Here we review the general principles of neuronal translation, focusing on the particular relevance of several key regulators of nervous system translation, including eukaryotic initiation factor 2α (eIF2α), the mechanistic (or mammalian) target of rapamycin complex 1 (mTORC1), and the eukaryotic elongation factor 2 (eEF2). These pathways regulate the overall rate of protein synthesis in neurons and have selective effects on the translation of specific messenger RNAs (mRNAs). The importance of these general and specific translational control mechanisms is considered in the normal functioning of the nervous system, particularly during synaptic plasticity underlying memory, and in the context of neurological disorders.}, } @article {pmid30082468, year = {2018}, author = {Biswas, J and Liu, Y and Singer, RH and Wu, B}, title = {Fluorescence Imaging Methods to Investigate Translation in Single Cells.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032722}, pmid = {30082468}, issn = {1943-0264}, abstract = {Translation is the fundamental biological process that converts the genetic information in messenger RNAs (mRNAs) into functional proteins. Translation regulation allows cells to control when, where, and how many proteins are synthesized. Much of what we know about translation comes from ensemble approaches that measure the average of many cells. The cellular and molecular heterogeneity in the regulation of translation remains largely elusive. Fluorescence microscopy allows interrogation of biological problems with single-molecule, single-cell sensitivity. In recent years, improved design of reagents and microscopy tools has led to improved spatial and temporal resolution of translation imaging. It is now possible to track global translation in specific subcellular compartments and follow the translation dynamics of single transcripts. Highlighted here is the recent progress in translation imaging with emphasis on in vivo translation dynamics. These tools will be invaluable to the study of translation regulation.}, } @article {pmid30082467, year = {2018}, author = {Teixeira, FK and Lehmann, R}, title = {Translational Control during Developmental Transitions.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032987}, pmid = {30082467}, issn = {1943-0264}, abstract = {The many steps of gene expression, from the transcription of a gene to the production of its protein product, are well understood. Yet, transcriptional regulation has been the focal point for the study of gene expression during development. However, quantitative studies reveal that messenger RNA (mRNA) levels are not necessarily good predictors of the respective proteins' levels in a cell. This discrepancy is, at least in part, the result of developmentally regulated, translational mechanisms that control the spatiotemporal regulation of gene expression. In this review, we focus on translational regulatory mechanisms mediating global transitions in gene expression: the shift from the maternal to the embryonic developmental program in the early embryo and the switch from the self-renewal of stem cells to differentiation in the adult.}, } @article {pmid30082466, year = {2018}, author = {Tahmasebi, S and Sonenberg, N and Hershey, JWB and Mathews, MB}, title = {Protein Synthesis and Translational Control: A Historical Perspective.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a035584}, pmid = {30082466}, issn = {1943-0264}, abstract = {Protein synthesis and its regulation are central to all known forms of life and impinge on biological arenas as varied as agriculture, biotechnology, and medicine. Otherwise known as translation and translational control, these processes have been investigated with increasing intensity since the middle of the 20th century, and in increasing depth with advances in molecular and cell biology. We review the origins of the field, focusing on the underlying concepts and early studies of the cellular machinery and mechanisms involved. We highlight key discoveries and events on a timeline, consider areas where current research has engendered new ideas, and conclude with some speculation on future directions for the field.}, } @article {pmid30082465, year = {2018}, author = {Chekulaeva, M and Rajewsky, N}, title = {Roles of Long Noncoding RNAs and Circular RNAs in Translation.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032680}, pmid = {30082465}, issn = {1943-0264}, abstract = {Most of the eukaryotic genome is pervasively transcribed, yielding hundreds to thousands of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs), some of which are well conserved during evolution. Functions have been described for a few lncRNAs and circRNAs but remain elusive for most. Both classes of RNAs play regulatory roles in translation by interacting with messenger RNAs (mRNAs), microRNAs (miRNAs), or mRNA-binding proteins (RBPs), thereby modulating translation in trans Moreover, although initially defined as noncoding, a number of lncRNAs and circRNAs have recently been reported to contain functional open reading frames (ORFs). Here, we review current understanding of the roles played by lncRNAs and circRNAs in protein synthesis and discuss challenges and open questions in the field.}, } @article {pmid30082464, year = {2018}, author = {Ivanov, P and Kedersha, N and Anderson, P}, title = {Stress Granules and Processing Bodies in Translational Control.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032813}, pmid = {30082464}, issn = {1943-0264}, abstract = {Stress granules (SGs) and processing bodies (PBs) are non-membrane-enclosed RNA granules that dynamically sequester translationally inactive messenger ribonucleoprotein particles (mRNPs) into compartments that are distinct from the surrounding cytoplasm. mRNP remodeling, silencing, and/or storage involves the dynamic partitioning of closed-loop polyadenylated mRNPs into SGs, or the sequestration of deadenylated, linear mRNPs into PBs. SGs form when stress-activated pathways stall translation initiation but allow elongation and termination to occur normally, resulting in a sudden excess of mRNPs that are spatially condensed into discrete foci by protein:protein, protein:RNA, and RNA:RNA interactions. In contrast, PBs can exist in the absence of stress, when specific factors promote mRNA deadenylation, condensation, and sequestration from the translational machinery. The formation and dissolution of SGs and PBs reflect changes in messenger RNA (mRNA) metabolism and allow cells to modulate the proteome and/or mediate life or death decisions during changing environmental conditions.}, } @article {pmid30082412, year = {2018}, author = {Talhouarne, GJS and Gall, JG}, title = {Lariat intronic RNAs in the cytoplasm of vertebrate cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7970-E7977}, pmid = {30082412}, issn = {1091-6490}, support = {R01 GM033397/GM/NIGMS NIH HHS/United States ; T32 GM007231/GM/NIGMS NIH HHS/United States ; }, mesh = {3T3 Cells ; Active Transport, Cell Nucleus/physiology ; Animals ; Cell Nucleus/genetics/*metabolism ; Chickens ; Cytoplasm/genetics/*metabolism ; Drosophila ; HeLa Cells ; Humans ; Mice ; RNA, Untranslated/genetics/*metabolism ; Xenopus ; Zebrafish ; }, abstract = {Most intronic RNAs are degraded within seconds or minutes after their excision from newly formed transcripts. However, stable intronic sequence RNAs (sisRNAs) have been described from oocytes of the frog Xenopus, from Drosophila embryos, and from human cell lines. In Xenopus oocytes, sisRNAs are abundant in both the nucleus and cytoplasm, they occur in the form of lariats, and they are stable for days. In this study we demonstrate that cytoplasmic sisRNAs are also found in human, mouse, chicken, and zebrafish cells. They exist as circular (lariat) molecules, mostly 100-500 nucleotides in length, and are derived from many housekeeping genes. They tend to have an unusual cytosine branchpoint (with the exception of those from the frog). Stable lariats are exported from the nucleus to the cytoplasm by the NXF1/NXT1 system, demonstrating that their presence in the cytoplasm is not due to passive diffusion. Lariats in the cytoplasm are not associated with transcripts of the genes from which they are derived. The biological significance of cytoplasmic sisRNAs remains obscure.}, } @article {pmid30082411, year = {2018}, author = {Petrova, B and Liu, K and Tian, C and Kitaoka, M and Freinkman, E and Yang, J and Orr-Weaver, TL}, title = {Dynamic redox balance directs the oocyte-to-embryo transition via developmentally controlled reactive cysteine changes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7978-E7986}, pmid = {30082411}, issn = {1091-6490}, support = {R35 GM118098/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle/*physiology ; Cysteine/genetics/*metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster ; Embryo, Nonmammalian/cytology/*metabolism ; Embryonic Development/*physiology ; Membrane Proteins/genetics/metabolism ; Mutation ; Oocytes/cytology/*metabolism ; Oxidation-Reduction ; Thioredoxins/genetics/metabolism ; }, abstract = {The metabolic and redox state changes during the transition from an arrested oocyte to a totipotent embryo remain uncharacterized. Here, we applied state-of-the-art, integrated methodologies to dissect these changes in Drosophila We demonstrate that early embryos have a more oxidized state than mature oocytes. We identified specific alterations in reactive cysteines at a proteome-wide scale as a result of this metabolic and developmental transition. Consistent with a requirement for redox change, we demonstrate a role for the ovary-specific thioredoxin Deadhead (DHD). dhd-mutant oocytes are prematurely oxidized and exhibit meiotic defects. Epistatic analyses with redox regulators link dhd function to the distinctive redox-state balance set at the oocyte-to-embryo transition. Crucially, global thiol-redox profiling identified proteins whose cysteines became differentially modified in the absence of DHD. We validated these potential DHD substrates by recovering DHD-interaction partners using multiple approaches. One such target, NO66, is a conserved protein that genetically interacts with DHD, revealing parallel functions. As redox changes also have been observed in mammalian oocytes, we hypothesize a link between developmental control of this cell-cycle transition and regulation by metabolic cues. This link likely operates both by general redox state and by changes in the redox state of specific proteins. The redox proteome defined here is a valuable resource for future investigation of the mechanisms of redox-modulated control at the oocyte-to-embryo transition.}, } @article {pmid30082410, year = {2018}, author = {}, title = {Correction for Nojiri et al., Atrial natriuretic peptide prevents cancer metastasis through vascular endothelial cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7883-E7886}, doi = {10.1073/pnas.1811802115}, pmid = {30082410}, issn = {1091-6490}, } @article {pmid30082409, year = {2018}, author = {Steffen, W and Rockström, J and Richardson, K and Lenton, TM and Folke, C and Liverman, D and Summerhayes, CP and Barnosky, AD and Cornell, SE and Crucifix, M and Donges, JF and Fetzer, I and Lade, SJ and Scheffer, M and Winkelmann, R and Schellnhuber, HJ}, title = {Trajectories of the Earth System in the Anthropocene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8252-8259}, pmid = {30082409}, issn = {1091-6490}, abstract = {We explore the risk that self-reinforcing feedbacks could push the Earth System toward a planetary threshold that, if crossed, could prevent stabilization of the climate at intermediate temperature rises and cause continued warming on a "Hothouse Earth" pathway even as human emissions are reduced. Crossing the threshold would lead to a much higher global average temperature than any interglacial in the past 1.2 million years and to sea levels significantly higher than at any time in the Holocene. We examine the evidence that such a threshold might exist and where it might be. If the threshold is crossed, the resulting trajectory would likely cause serious disruptions to ecosystems, society, and economies. Collective human action is required to steer the Earth System away from a potential threshold and stabilize it in a habitable interglacial-like state. Such action entails stewardship of the entire Earth System-biosphere, climate, and societies-and could include decarbonization of the global economy, enhancement of biosphere carbon sinks, behavioral changes, technological innovations, new governance arrangements, and transformed social values.}, } @article {pmid30082408, year = {2018}, author = {Ni, X and Groffman, PM}, title = {Declines in methane uptake in forest soils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8587-8590}, pmid = {30082408}, issn = {1091-6490}, mesh = {*Forests ; Maryland ; Methane/*metabolism ; *Models, Biological ; *Soil ; }, abstract = {Forest soils are a sink for atmospheric methane (CH4) and play an important role in modulating the global CH4 budget. However, whether CH4 uptake by forest soils is affected by global environmental change is unknown. We measured soil to atmosphere net CH4 fluxes in temperate forests at two long-term ecological research sites in the northeastern United States from the late 1990s to the mid-2010s. We found that annual soil CH4 uptake decreased by 62% and 53% in urban and rural forests in Baltimore, Maryland and by 74% and 89% in calcium-fertilized and reference forests at Hubbard Brook, New Hampshire over this period. This decrease occurred despite marked declines in nitrogen deposition and increases in atmospheric CH4 concentration and temperature, which should lead to increases in CH4 uptake. This decrease in soil CH4 uptake appears to be driven by increases in precipitation and soil hydrological flux. Furthermore, an analysis of CH4 uptake around the globe showed that CH4 uptake in forest soils has decreased by an average of 77% from 1988 to 2015, particularly in forests located from 0 to 60 °N latitude where precipitation has been increasing. We conclude that the soil CH4 sink may be declining and overestimated in several regions across the globe.}, } @article {pmid30082407, year = {2018}, author = {Ficklin, DL and Abatzoglou, JT and Robeson, SM and Null, SE and Knouft, JH}, title = {Natural and managed watersheds show similar responses to recent climate change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8553-8557}, pmid = {30082407}, issn = {1091-6490}, abstract = {Changes in climate are driving an intensification of the hydrologic cycle and leading to alterations of natural streamflow regimes. Human disturbances such as dams, land-cover change, and water diversions are thought to obscure climate signals in hydrologic systems. As a result, most studies of changing hydroclimatic conditions are limited to areas with natural streamflow. Here, we compare trends in observed streamflow from natural and human-modified watersheds in the United States and Canada for the 1981-2015 water years to evaluate whether comparable responses to climate change are present in both systems. We find that patterns and magnitudes of trends in median daily streamflow, daily streamflow variability, and daily extremes in human-modified watersheds are similar to those from nearby natural watersheds. Streamflow in both systems show negative trends throughout the southern and western United States and positive trends throughout the northeastern United States, the northern Great Plains, and southern prairies of Canada. The trends in both natural and human-modified watersheds are linked to local trends in precipitation and reference evapotranspiration, demonstrating that water management and land-cover change have not substantially altered the effects of climate change on human-modified watersheds compared with nearby natural watersheds.}, } @article {pmid30082406, year = {2018}, author = {Greenwood, BN and Carnahan, S and Huang, L}, title = {Patient-physician gender concordance and increased mortality among female heart attack patients.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8569-8574}, pmid = {30082406}, issn = {1091-6490}, mesh = {Female ; Florida/epidemiology ; Humans ; Male ; Myocardial Infarction/*mortality/therapy ; Retrospective Studies ; *Sex Characteristics ; }, abstract = {We examine patient gender disparities in survival rates following acute myocardial infarctions (i.e., heart attacks) based on the gender of the treating physician. Using a census of heart attack patients admitted to Florida hospitals between 1991 and 2010, we find higher mortality among female patients who are treated by male physicians. Male patients and female patients experience similar outcomes when treated by female physicians, suggesting that unique challenges arise when male physicians treat female patients. We further find that male physicians with more exposure to female patients and female physicians have more success treating female patients.}, } @article {pmid30082405, year = {2018}, author = {Jiang, Z and Zhang, S and Klausen, LH and Song, J and Li, Q and Wang, Z and Stokke, BT and Huang, Y and Besenbacher, F and Nielsen, LP and Dong, M}, title = {In vitro single-cell dissection revealing the interior structure of cable bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8517-8522}, pmid = {30082405}, issn = {1091-6490}, mesh = {*Bacterial Physiological Phenomena ; Biological Transport, Active/physiology ; Deltaproteobacteria/*physiology ; *Water Microbiology ; }, abstract = {Filamentous Desulfobulbaceae bacteria were recently discovered as long-range transporters of electrons from sulfide to oxygen in marine sediments. The long-range electron transfer through these cable bacteria has created considerable interests, but it has also raised many questions, such as what structural basis will be required to enable micrometer-sized cells to build into centimeter-long continuous filaments? Here we dissected cable bacteria cells in vitro by atomic force microscopy and further explored the interior, which is normally hidden behind the outer membrane. Using nanoscale topographical and mechanical maps, different types of bacterial cell-cell junctions and strings along the cable length were identified. More important, these strings were found to be continuous along the bacterial cells passing through the cell-cell junctions. This indicates that the strings serve an important function in maintaining integrity of individual cable bacteria cells as a united filament. Furthermore, ridges in the outer membrane are found to envelop the individual strings at cell-cell junctions, and they are proposed to strengthen the junctions. Finally, we propose a model for the division and growth of the cable bacteria, which illustrate the possible structural requirements for the formation of centimeter-length filaments in the recently discovered cable bacteria.}, } @article {pmid30082404, year = {2018}, author = {Simon, M and Schwartz, C and Hudson, D and Johnson, SD}, title = {A data-driven computational model on the effects of immigration policies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7914-E7923}, pmid = {30082404}, issn = {1091-6490}, abstract = {Many scholars suggest that visa restrictions push individuals who would have otherwise migrated legally toward illegal channels. This expectation is difficult to test empirically for three reasons. First, unauthorized migration is clandestine and often unobservable. Second, interpersonal ties between migrants and would-be migrants form a self-perpetuating system, which adapts in ways that are difficult to observe or predict. Third, empirical evaluations of immigration policy are vulnerable to endogeneity and other issues of causal inference. In this paper, we pair tailor-made empirical designs with an agent-based computational model (ABM) to capture the dynamics of a migration system that often elude empirical analysis, while grounding agent rules and characteristics with primary data collected in Jamaica, an origin country. We find that some government-imposed restrictions on migrants can deter total migration, but others are ineffective. Relative to a system of free movement, the minimal eligibility conditions required to classify migrants into visa categories alone make migration inaccessible for many. Restrictive policies imposed on student and high-skilled visa categories have little added effect because eligible individuals are likely able to migrate through alternative legal categories. Meanwhile, restrictions on family-based visas result in significant reductions in total migration. However, they also produce the largest reorientation toward unauthorized channels-an unintended consequence that even the highest rates of apprehension do not effectively eliminate.}, } @article {pmid30082403, year = {2018}, author = {Löber, U and Hobbs, M and Dayaram, A and Tsangaras, K and Jones, K and Alquezar-Planas, DE and Ishida, Y and Meers, J and Mayer, J and Quedenau, C and Chen, W and Johnson, RN and Timms, P and Young, PR and Roca, AL and Greenwood, AD}, title = {Degradation and remobilization of endogenous retroviruses by recombination during the earliest stages of a germ-line invasion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8609-8614}, pmid = {30082403}, issn = {1091-6490}, support = {R01 GM092706/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Endogenous Retroviruses/*genetics ; Female ; Male ; New South Wales ; Phascolarctidae/*genetics ; *Recombination, Genetic ; }, abstract = {Endogenous retroviruses (ERVs) are proviral sequences that result from colonization of the host germ line by exogenous retroviruses. The majority of ERVs represent defective retroviral copies. However, for most ERVs, endogenization occurred millions of years ago, obscuring the stages by which ERVs become defective and the changes in both virus and host important to the process. The koala retrovirus, KoRV, only recently began invading the germ line of the koala (Phascolarctos cinereus), permitting analysis of retroviral endogenization on a prospective basis. Here, we report that recombination with host genomic elements disrupts retroviruses during the earliest stages of germ-line invasion. One type of recombinant, designated recKoRV1, was formed by recombination of KoRV with an older degraded retroelement. Many genomic copies of recKoRV1 were detected across koalas. The prevalence of recKoRV1 was higher in northern than in southern Australian koalas, as is the case for KoRV, with differences in recKoRV1 prevalence, but not KoRV prevalence, between inland and coastal New South Wales. At least 15 additional different recombination events between KoRV and the older endogenous retroelement generated distinct recKoRVs with different geographic distributions. All of the identified recombinant viruses appear to have arisen independently and have highly disrupted ORFs, which suggests that recombination with existing degraded endogenous retroelements may be a means by which replication-competent ERVs that enter the germ line are degraded.}, } @article {pmid30082402, year = {2018}, author = {}, title = {Correction for Kang and Lubensky, Chiral twist drives raft formation and organization in membranes composed of rod-like particles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7881}, doi = {10.1073/pnas.1812385115}, pmid = {30082402}, issn = {1091-6490}, } @article {pmid30082401, year = {2018}, author = {Iknayan, KJ and Beissinger, SR}, title = {Collapse of a desert bird community over the past century driven by climate change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8597-8602}, pmid = {30082401}, issn = {1091-6490}, mesh = {Animals ; Birds/*physiology ; *Climate Change ; *Desert Climate ; *Extinction, Biological ; *Models, Biological ; }, abstract = {Climate change has caused deserts, already defined by climatic extremes, to warm and dry more rapidly than other ecoregions in the contiguous United States over the last 50 years. Desert birds persist near the edge of their physiological limits, and climate change could cause lethal dehydration and hyperthermia, leading to decline or extirpation of some species. We evaluated how desert birds have responded to climate and habitat change by resurveying historic sites throughout the Mojave Desert that were originally surveyed for avian diversity during the early 20th century by Joseph Grinnell and colleagues. We found strong evidence of an avian community in collapse. Sites lost on average 43% of their species, and occupancy probability declined significantly for 39 of 135 breeding birds. The common raven was the only native species to substantially increase across survey sites. Climate change, particularly decline in precipitation, was the most important driver of site-level persistence, while habitat change had a secondary influence. Habitat preference and diet were the two most important species traits associated with occupancy change. The presence of surface water reduced the loss of site-level richness, creating refugia. The collapse of the avian community over the past century may indicate a larger imbalance in the Mojave and provide an early warning of future ecosystem disintegration, given climate models unanimously predict an increasingly dry and hot future.}, } @article {pmid30082400, year = {2018}, author = {Tartèse, R and Chaussidon, M and Gurenko, A and Delarue, F and Robert, F}, title = {Insights into the origin of carbonaceous chondrite organics from their triple oxygen isotope composition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8535-8540}, pmid = {30082400}, issn = {1091-6490}, abstract = {Dust grains of organic matter were the main reservoir of C and N in the forming Solar System and are thus considered to be an essential ingredient for the emergence of life. However, the physical environment and the chemical mechanisms at the origin of these organic grains are still highly debated. In this study, we report high-precision triple oxygen isotope composition for insoluble organic matter isolated from three emblematic carbonaceous chondrites, Orgueil, Murchison, and Cold Bokkeveld. These results suggest that the O isotope composition of carbonaceous chondrite insoluble organic matter falls on a slope 1 correlation line in the triple oxygen isotope diagram. The lack of detectable mass-dependent O isotopic fractionation, indicated by the slope 1 line, suggests that the bulk of carbonaceous chondrite organics did not form on asteroidal parent bodies during low-temperature hydrothermal events. On the other hand, these O isotope data, together with the H and N isotope characteristics of insoluble organic matter, may indicate that parent bodies of different carbonaceous chondrite types largely accreted organics formed locally in the protosolar nebula, possibly by photochemical dissociation of C-rich precursors.}, } @article {pmid30082399, year = {2018}, author = {Shankar, GM and Kirtane, AR and Miller, JJ and Mazdiyasni, H and Rogner, J and Tai, T and Williams, EA and Higuchi, F and Juratli, TA and Tateishi, K and Koerner, MVA and Tummala, SS and Fink, AL and Penson, T and Schmidt, SP and Wojtkiewicz, GR and Baig, A and Francis, JM and Rinne, ML and Batten, JM and Batchelor, TT and Brastianos, PK and Curry, WT and Barker, FG and Jordan, JT and Iafrate, AJ and Chi, AS and Lennerz, JK and Meyerson, M and Langer, R and Wakimoto, H and Traverso, G and Cahill, DP}, title = {Genotype-targeted local therapy of glioma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8388-E8394}, pmid = {30082399}, issn = {1091-6490}, support = {R01 CA227821/CA/NCI NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Brain Neoplasms/drug therapy/enzymology/genetics ; Cyanides/*pharmacology ; Drug Delivery Systems/methods ; Female ; *Genotype ; *Glioma/drug therapy/enzymology/genetics ; Guanidines/*pharmacology ; Humans ; Isocitrate Dehydrogenase/*genetics ; Male ; Mice ; Mice, SCID ; Molecular Targeted Therapy/*methods ; *Mutation ; Neoplasm Proteins/*genetics ; Xenograft Model Antitumor Assays ; }, abstract = {Aggressive neurosurgical resection to achieve sustained local control is essential for prolonging survival in patients with lower-grade glioma. However, progression in many of these patients is characterized by local regrowth. Most lower-grade gliomas harbor isocitrate dehydrogenase 1 (IDH1) or IDH2 mutations, which sensitize to metabolism-altering agents. To improve local control of IDH mutant gliomas while avoiding systemic toxicity associated with metabolic therapies, we developed a precision intraoperative treatment that couples a rapid multiplexed genotyping tool with a sustained release microparticle (MP) drug delivery system containing an IDH-directed nicotinamide phosphoribosyltransferase (NAMPT) inhibitor (GMX-1778). We validated our genetic diagnostic tool on clinically annotated tumor specimens. GMX-1778 MPs showed mutant IDH genotype-specific toxicity in vitro and in vivo, inducing regression of orthotopic IDH mutant glioma murine models. Our strategy enables immediate intraoperative genotyping and local application of a genotype-specific treatment in surgical scenarios where local tumor control is paramount and systemic toxicity is therapeutically limiting.}, } @article {pmid30082398, year = {2018}, author = {Mahan, B and Moynier, F and Siebert, J and Gueguen, B and Agranier, A and Pringle, EA and Bollard, J and Connelly, JN and Bizzarro, M}, title = {Volatile element evolution of chondrules through time.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8547-8552}, pmid = {30082398}, issn = {1091-6490}, support = {616027//European Research Council/International ; }, abstract = {Chondrites and their main components, chondrules, are our guides into the evolution of the Solar System. Investigating the history of chondrules, including their volatile element history and the prevailing conditions of their formation, has implications not only for the understanding of chondrule formation and evolution but for that of larger bodies such as the terrestrial planets. Here we have determined the bulk chemical composition-rare earth, refractory, main group, and volatile element contents-of a suite of chondrules previously dated using the Pb-Pb system. The volatile element contents of chondrules increase with time from ∼1 My after Solar System formation, likely the result of mixing with a volatile-enriched component during chondrule recycling. Variations in the Mn/Na ratios signify changes in redox conditions over time, suggestive of decoupled oxygen and volatile element fugacities, and indicating a decrease in oxygen fugacity and a relative increase in the fugacities of in-fluxing volatiles with time. Within the context of terrestrial planet formation via pebble accretion, these observations corroborate the early formation of Mars under relatively oxidizing conditions and the protracted growth of Earth under more reducing conditions, and further suggest that water and volatile elements in the inner Solar System may not have arrived pairwise.}, } @article {pmid30082397, year = {2018}, author = {Xu, J and Dong, Q and Yu, Y and Niu, B and Ji, D and Li, M and Huang, Y and Chen, X and Tan, A}, title = {Mass spider silk production through targeted gene replacement in Bombyx mori.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {35}, pages = {8757-8762}, pmid = {30082397}, issn = {1091-6490}, support = {27304C2054/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; *Animals, Genetically Modified/genetics/metabolism ; *Bombyx/genetics/metabolism ; *Fibroins/biosynthesis/genetics ; *Genetic Engineering ; Spiders/*genetics ; }, abstract = {Spider silk is one of the best natural fibers and has superior mechanical properties. However, the large-scale harvesting of spider silk by rearing spiders is not feasible, due to their territorial and cannibalistic behaviors. The silkworm, Bombyx mori, has been the most well known silk producer for thousands of years and has been considered an ideal bioreactor for producing exogenous proteins, including spider silk. Previous attempts using transposon-mediated transgenic silkworms to produce spider silk could not achieve efficient yields, due to variable promoter activities and endogenous silk fibroin protein expression. Here, we report a massive spider silk production system in B. mori by using transcription activator-like effector nuclease-mediated homology-directed repair to replace the silkworm fibroin heavy chain gene (FibH) with the major ampullate spidroin-1 gene (MaSp1) in the spider Nephila clavipes We successfully replaced the ∼16-kb endogenous FibH gene with a 1.6-kb MaSp1 gene fused with a 1.1-kb partial FibH sequence and achieved up to 35.2% chimeric MaSp1 protein amounts in transformed cocoon shells. The presence of the MaSp1 peptide significantly changed the mechanical characteristics of the silk fiber, especially the extensibility. Our study provides a native promoter-driven, highly efficient system for expressing the heterologous spider silk gene instead of the transposon-based, random insertion of the spider gene into the silkworm genome. Targeted MaSp1 integration into silkworm silk glands provides a paradigm for the large-scale production of spider silk protein with genetically modified silkworms, and this approach will shed light on developing new biomaterials.}, } @article {pmid30082396, year = {2018}, author = {Wang, D and Eberhart, MS and Sheridan, MV and Hu, K and Sherman, BD and Nayak, A and Wang, Y and Marquard, SL and Dares, CJ and Meyer, TJ}, title = {Stabilized photoanodes for water oxidation by integration of organic dyes, water oxidation catalysts, and electron-transfer mediators.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8523-8528}, pmid = {30082396}, issn = {1091-6490}, abstract = {Stabilized photoanodes for light-driven water oxidation have been prepared on nanoparticle core/shell electrodes with surface-stabilized donor-acceptor chromophores, a water oxidation catalyst, and an electron-transfer mediator. For the electrode, fluorine-doped tin oxide FTO|SnO2/TiO2|-Org1-|1.1 nm Al2O3|-RuP2+-WOC (water oxidation catalyst) with Org1 (1-cyano-2-(4-(diphenylamino)phenyl)vinyl)phosphonic acid), the mediator RuP2+ ([Ru(4,4-(PO3H2)2-2,2-bipyridine)(2,2-bipyridine)2]2+), and the WOC, Ru(bda)(py(CH2)(3or10)P(O3H)2)2 (bda is 2,2-bipyridine-6,6-dicarboxylate with x = 3 or 10), solar excitation resulted in photocurrents of ∼500 µA/cm2 and quantitative O2 evolution at pH 4.65. Related results were obtained for other Ru(II) polypyridyl mediators. For the organic dye PP (5-(4-(dihydroxyphosphoryl)phenyl)-10,15,20-Tris(mesityl)porphyrin), solar water oxidation occurred with a driving force near 0 V.}, } @article {pmid30082395, year = {2018}, author = {Abarzhi, SI and Ilyin, DV and Goddard, WA and Anisimov, SI}, title = {Interface dynamics: Mechanisms of stabilization and destabilization and structure of flow fields.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1714500115}, pmid = {30082395}, issn = {1091-6490}, abstract = {Interfacial mixing and transport are nonequilibrium processes coupling kinetic to macroscopic scales. They occur in fluids, plasmas, and materials over celestial events to atoms. Grasping their fundamentals can advance a broad range of disciplines in science, mathematics, and engineering. This paper focuses on the long-standing classic problem of stability of a phase boundary-a fluid interface that has a mass flow across it. We briefly review the recent advances in theoretical and experimental studies, develop the general theoretical framework directly linking the microscopic interfacial transport to the macroscopic flow fields, discover mechanisms of interface stabilization and destabilization that have not been discussed before for both inertial and accelerated dynamics, and chart perspectives for future research.}, } @article {pmid30082394, year = {2018}, author = {Shrivastava, A and Patel, VK and Tang, Y and Yost, SC and Dewhirst, FE and Berg, HC}, title = {Cargo transport shapes the spatial organization of a microbial community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8633-8638}, pmid = {30082394}, issn = {1091-6490}, support = {K99 DE026826/DE/NIDCR NIH HHS/United States ; R01 AI016478/AI/NIAID NIH HHS/United States ; }, mesh = {Capnocytophaga/*physiology ; Humans ; Microbial Consortia/*physiology ; Microbiota/*physiology ; Mouth/*microbiology ; }, abstract = {The human microbiome is an assemblage of diverse bacteria that interact with one another to form communities. Bacteria in a given community are arranged in a 3D matrix with many degrees of freedom. Snapshots of the community display well-defined structures, but the steps required for their assembly are not understood. Here, we show that this construction is carried out with the help of gliding bacteria. Gliding is defined as the motion of cells over a solid or semisolid surface without the necessity of growth or the aid of pili or flagella. Genomic analysis suggests that gliding bacteria are present in human microbial communities. We focus on Capnocytophaga gingivalis, which is present in abundance in the human oral microbiome. Tracking of fluorescently labeled single cells and of gas bubbles carried by fluid flow shows that swarms of C. gingivalis are layered, with cells in the upper layers moving more rapidly than those in the lower layers. Thus, cells also glide on top of one another. Cells of nonmotile bacterial species attach to the surface of C. gingivalis and are propelled as cargo. The cargo cell moves along the length of a C. gingivalis cell, looping from one pole to the other. Multicolor fluorescent spectral imaging of cells of different live but nonmotile bacterial species reveals their long-range transport in a polymicrobial community. A swarm of C. gingivalis transports some nonmotile bacterial species more efficiently than others and helps to shape the spatial organization of a polymicrobial community.}, } @article {pmid30082393, year = {2018}, author = {Marks, SM and Patel, AJ}, title = {Antifreeze protein hydration waters: Unstructured unless bound to ice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8244-8246}, pmid = {30082393}, issn = {1091-6490}, mesh = {*Antifreeze Proteins ; *Ice ; Water ; }, } @article {pmid30082392, year = {2018}, author = {Mittal, P and Brindle, J and Stephen, J and Plotkin, JB and Kudla, G}, title = {Codon usage influences fitness through RNA toxicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8639-8644}, pmid = {30082392}, issn = {1091-6490}, support = {MC_UU_12018/23//Medical Research Council/United Kingdom ; 097383//Wellcome Trust/United Kingdom ; 207507//Wellcome Trust/United Kingdom ; }, mesh = {Codon/genetics/*metabolism ; Escherichia coli/genetics/*metabolism ; *Mutation ; RNA, Bacterial/genetics/*metabolism ; }, abstract = {Many organisms are subject to selective pressure that gives rise to unequal usage of synonymous codons, known as codon bias. To experimentally dissect the mechanisms of selection on synonymous sites, we expressed several hundred synonymous variants of the GFP gene in Escherichia coli, and used quantitative growth and viability assays to estimate bacterial fitness. Unexpectedly, we found many synonymous variants whose expression was toxic to E. coli Unlike previously studied effects of synonymous mutations, the effect that we discovered is independent of translation, but it depends on the production of toxic mRNA molecules. We identified RNA sequence determinants of toxicity and evolved suppressor strains that can tolerate the expression of toxic GFP variants. Genome sequencing of these suppressor strains revealed a cluster of promoter mutations that prevented toxicity by reducing mRNA levels. We conclude that translation-independent RNA toxicity is a previously unrecognized obstacle in bacterial gene expression.}, } @article {pmid30082391, year = {2018}, author = {Fang, Y and Ran, S and Xie, W and Wang, S and Meng, YS and Maple, MB}, title = {Evidence for a conducting surface ground state in high-quality single crystalline FeSi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8558-8562}, pmid = {30082391}, issn = {1091-6490}, abstract = {We report anomalous physical properties of high-quality single-crystalline FeSi over a wide temperature range of 1.8-400 K. The electrical resistivity ρ(T) can be described by activated behavior with an energy gap Δ = 57 meV between 150 and 67 K, below which the estimated energy gap is significantly smaller. The magneto-resistivity and Hall coefficient change sign in the vicinity of 67 K, suggesting a change of dominant charge carriers. At ∼19 K, ρ(T) undergoes a cross-over from semiconducting to metallic behavior which is very robust against external magnetic fields. The low-temperature metallic conductivity depends strongly on the width/thickness of the sample. In addition, no indication of a bulk-phase transition or onset of magnetic order is found down to 2 K from specific heat and magnetic susceptibility measurements. The measurements are consistent with one another and point to complex electronic transport behavior that apparently involves a conducting surface state in FeSi at low temperatures, suggesting the possibility that FeSi is a 3D topological insulator.}, } @article {pmid30082390, year = {2018}, author = {Gistelinck, C and Kwon, RY and Malfait, F and Symoens, S and Harris, MP and Henke, K and Hawkins, MB and Fisher, S and Sips, P and Guillemyn, B and Bek, JW and Vermassen, P and De Saffel, H and Witten, PE and Weis, M and De Paepe, A and Eyre, DR and Willaert, A and Coucke, PJ}, title = {Zebrafish type I collagen mutants faithfully recapitulate human type I collagenopathies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8037-E8046}, pmid = {30082390}, issn = {1091-6490}, support = {U01 DE024434/DE/NIDCR NIH HHS/United States ; P40 RR012546/RR/NCRR NIH HHS/United States ; R01 AR037318/AR/NIAMS NIH HHS/United States ; R37 AR036794/AR/NIAMS NIH HHS/United States ; R37 AR037318/AR/NIAMS NIH HHS/United States ; R01 AR072199/AR/NIAMS NIH HHS/United States ; R01 AR036794/AR/NIAMS NIH HHS/United States ; K01 AR066061/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; *Collagen Type I/genetics/metabolism ; *Disease Models, Animal ; *Ehlers-Danlos Syndrome/genetics/metabolism/pathology ; Humans ; *Osteogenesis Imperfecta/genetics/metabolism/pathology ; *Zebrafish/genetics/metabolism ; }, abstract = {The type I collagenopathies are a group of heterogeneous connective tissue disorders, that are caused by mutations in the genes encoding type I collagen and include specific forms of osteogenesis imperfecta (OI) and the Ehlers-Danlos syndrome (EDS). These disorders present with a broad disease spectrum and large clinical variability of which the underlying genetic basis is still poorly understood. In this study, we systematically analyzed skeletal phenotypes in a large set of zebrafish, with diverse mutations in the genes encoding type I collagen, representing different genetic forms of human OI, and a zebrafish model resembling human EDS, which harbors a number of soft connective tissues defects, typical of EDS. Furthermore, we provide insight into how zebrafish and human type I collagen are compositionally and functionally related, which is relevant in the interpretation of human type I collagen-related disease models. Our studies reveal a high degree of intergenotype variability in phenotypic expressivity that closely correlates with associated OI severity. Furthermore, we demonstrate the potential for select mutations to give rise to phenotypic variability, mirroring the clinical variability associated with human disease pathology. Therefore, our work suggests the future potential for zebrafish to aid in identifying unknown genetic modifiers and mechanisms underlying the phenotypic variability in OI and related disorders. This will improve diagnostic strategies and enable the discovery of new targetable pathways for pharmacological intervention.}, } @article {pmid30082389, year = {2018}, author = {Han, J and Jentzen, A and E, W}, title = {Solving high-dimensional partial differential equations using deep learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8505-8510}, pmid = {30082389}, issn = {1091-6490}, abstract = {Developing algorithms for solving high-dimensional partial differential equations (PDEs) has been an exceedingly difficult task for a long time, due to the notoriously difficult problem known as the "curse of dimensionality." This paper introduces a deep learning-based approach that can handle general high-dimensional parabolic PDEs. To this end, the PDEs are reformulated using backward stochastic differential equations and the gradient of the unknown solution is approximated by neural networks, very much in the spirit of deep reinforcement learning with the gradient acting as the policy function. Numerical results on examples including the nonlinear Black-Scholes equation, the Hamilton-Jacobi-Bellman equation, and the Allen-Cahn equation suggest that the proposed algorithm is quite effective in high dimensions, in terms of both accuracy and cost. This opens up possibilities in economics, finance, operational research, and physics, by considering all participating agents, assets, resources, or particles together at the same time, instead of making ad hoc assumptions on their interrelationships.}, } @article {pmid30082388, year = {2018}, author = {Masch, JM and Steffens, H and Fischer, J and Engelhardt, J and Hubrich, J and Keller-Findeisen, J and D'Este, E and Urban, NT and Grant, SGN and Sahl, SJ and Kamin, D and Hell, SW}, title = {Robust nanoscopy of a synaptic protein in living mice by organic-fluorophore labeling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8047-E8056}, pmid = {30082388}, issn = {1091-6490}, mesh = {Animals ; Disks Large Homolog 4 Protein/genetics/*metabolism ; Luminescent Proteins/genetics/*metabolism ; Mice ; Optical Imaging/*methods ; Staining and Labeling/*methods ; Synapses/genetics/*metabolism ; *Visual Cortex/cytology/metabolism ; }, abstract = {Extending superresolution fluorescence microscopy to living animals has remained a challenging frontier ever since the first demonstration of STED (stimulated emission depletion) nanoscopy in the mouse visual cortex. The use of fluorescent proteins (FPs) in in vivo STED analyses has been limiting available fluorescence photon budgets and attainable image contrasts, in particular for far-red FPs. This has so far precluded the definition of subtle details in protein arrangements at sufficient signal-to-noise ratio. Furthermore, imaging with longer wavelengths holds promise for reducing photostress. Here, we demonstrate that a strategy based on enzymatic self-labeling of the HaloTag fusion protein by high-performance synthetic fluorophore labels provides a robust avenue to superior in vivo analysis with STED nanoscopy in the far-red spectral range. We illustrate our approach by mapping the nanoscale distributions of the abundant scaffolding protein PSD95 at the postsynaptic membrane of excitatory synapses in living mice. With silicon-rhodamine as the reporter fluorophore, we present imaging with high contrast and low background down to ∼70-nm lateral resolution in the visual cortex at ≤25-µm depth. This approach allowed us to identify and characterize the diversity of PSD95 scaffolds in vivo. Besides small round/ovoid shapes, a substantial fraction of scaffolds exhibited a much more complex spatial organization. This highly inhomogeneous, spatially extended PSD95 distribution within the disk-like postsynaptic density, featuring intricate perforations, has not been highlighted in cell- or tissue-culture experiments. Importantly, covisualization of the corresponding spine morphologies enabled us to contextualize the diverse PSD95 patterns within synapses of different orientations and sizes.}, } @article {pmid30082387, year = {2018}, author = {Foulds, CE}, title = {Disrupting a negative feedback loop drives endocrine therapy-resistant breast cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8236-8238}, pmid = {30082387}, issn = {1091-6490}, mesh = {Antineoplastic Agents, Hormonal ; Breast/*drug effects ; *Breast Neoplasms ; Drug Resistance, Neoplasm/drug effects ; Humans ; }, } @article {pmid30082386, year = {2018}, author = {Knoch, E and Sugawara, S and Mori, T and Poulsen, C and Fukushima, A and Harholt, J and Fujimoto, Y and Umemoto, N and Saito, K}, title = {Third DWF1 paralog in Solanaceae, sterol Δ24-isomerase, branches withanolide biosynthesis from the general phytosterol pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8096-E8103}, pmid = {30082386}, issn = {1091-6490}, support = {K08 MH001840/MH/NIMH NIH HHS/United States ; }, mesh = {Gene Expression Regulation, Enzymologic/*physiology ; Gene Expression Regulation, Plant/*physiology ; *Phylogeny ; *Plant Proteins/biosynthesis/genetics ; *Steroid Isomerases/biosynthesis/genetics ; *Withania/enzymology/genetics ; Withanolides/*metabolism ; }, abstract = {A large part of chemodiversity of plant triterpenes is due to the modification of their side chains. Reduction or isomerization of double bonds in the side chains is often an important step for the diversification of triterpenes, although the enzymes involved are not fully understood. Withanolides are a large group of structurally diverse C28 steroidal lactones derived from 24-methylenecholesterol. These compounds are found in the Indian medicinal plant Withania somnifera, also known as ashwagandha, and other members of the Solanaceae. The pathway for withanolide biosynthesis is unknown, preventing sustainable production via white biotechnology and downstream pharmaceutical usages. In the present study, based on genome and transcriptome data we have identified a key enzyme in the biosynthesis of withanolides: a DWF1 paralog encoding a sterol Δ24-isomerase (24ISO). 24ISO originated from DWF1 after two subsequent duplication events in Solanoideae plants. Withanolides and 24ISO appear only in the medicinal plants in the Solanoideae, not in crop plants such as potato and tomato, indicating negative selection during domestication. 24ISO is a unique isomerase enzyme evolved from a reductase and as such has maintained the FAD-binding oxidoreductase structure and requirement for NADPH. Using phylogenetic, metabolomic, and gene expression analysis in combination with heterologous expression and virus-induced gene silencing, we showed that 24ISO catalyzes the conversion of 24-methylenecholesterol to 24-methyldesmosterol. We propose that this catalytic step is the committing step in withanolide biosynthesis, opening up elucidation of the whole pathway and future larger-scale sustainable production of withanolides and related compounds with pharmacological properties.}, } @article {pmid30082385, year = {2018}, author = {Kamer, KJ and Sancak, Y and Fomina, Y and Meisel, JD and Chaudhuri, D and Grabarek, Z and Mootha, VK}, title = {MICU1 imparts the mitochondrial uniporter with the ability to discriminate between Ca2+ and Mn2+.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7960-E7969}, pmid = {30082385}, issn = {1091-6490}, support = {R00 HL124070/HL/NHLBI NIH HHS/United States ; R01 HL130143/HL/NHLBI NIH HHS/United States ; R01 HL141353/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans/genetics/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Calcium/*metabolism ; Calcium Channels/genetics/*metabolism ; Calcium-Binding Proteins/genetics/*metabolism ; Cation Transport Proteins/genetics/*metabolism ; HEK293 Cells ; Humans ; Ion Transport/physiology ; K562 Cells ; Manganese/*metabolism ; Mitochondrial Membrane Transport Proteins/genetics/*metabolism ; }, abstract = {The mitochondrial uniporter is a Ca2+-activated Ca2+ channel complex that displays exceptionally high conductance and selectivity. Here, we report cellular metal toxicity screens highlighting the uniporter's role in Mn2+ toxicity. Cells lacking the pore-forming uniporter subunit, MCU, are more resistant to Mn2+ toxicity, while cells lacking the Ca2+-sensing inhibitory subunit, MICU1, are more sensitive than the wild type. Consistent with these findings, Caenorhabditis elegans lacking the uniporter's pore have increased resistance to Mn2+ toxicity. The chemical-genetic interaction between uniporter machinery and Mn2+ toxicity prompted us to hypothesize that Mn2+ can indeed be transported by the uniporter's pore, but this transport is prevented by MICU1. To this end, we demonstrate that, in the absence of MICU1, both Mn2+ and Ca2+ can pass through the uniporter, as evidenced by mitochondrial Mn2+ uptake assays, mitochondrial membrane potential measurements, and mitoplast electrophysiology. We show that Mn2+ does not elicit the conformational change in MICU1 that is physiologically elicited by Ca2+, preventing Mn2+ from inducing the pore opening. Our work showcases a mechanism by which a channel's auxiliary subunit can contribute to its apparent selectivity and, furthermore, may have implications for understanding how manganese contributes to neurodegenerative disease.}, } @article {pmid30082384, year = {2018}, author = {Ovchinnikov, V and Stone, TA and Deber, CM and Karplus, M}, title = {Structure of the EmrE multidrug transporter and its use for inhibitor peptide design.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7932-E7941}, pmid = {30082384}, issn = {1091-6490}, support = {R03 AI111416/AI/NIAID NIH HHS/United States ; 376666//CIHR/Canada ; }, mesh = {*Antiporters/antagonists & inhibitors/chemistry ; Catalytic Domain ; *Drug Resistance, Multiple, Bacterial ; Escherichia coli/*chemistry ; *Escherichia coli Proteins/antagonists & inhibitors/chemistry ; *Molecular Dynamics Simulation ; Peptides/*chemistry ; *Protein Multimerization ; Protein Structure, Quaternary ; }, abstract = {Small multidrug resistance (SMR) pumps represent a minimal paradigm of proton-coupled membrane transport in bacteria, yet no high-resolution structure of an SMR protein is available. Here, atomic-resolution structures of the Escherichia coli efflux-multidrug resistance E (EmrE) multidrug transporter in ligand-bound form are refined using microsecond molecular dynamics simulations biased using low-resolution data from X-ray crystallography. The structures are compatible with existing mutagenesis data as well as NMR and biochemical experiments, including pKas of the catalytic glutamate residues and the dissociation constant ([Formula: see text]) of the tetraphenylphosphonium+ cation. The refined structures show the arrangement of residue side chains in the EmrE active site occupied by two different ligands and in the absence of a ligand, illustrating how EmrE can adopt structurally diverse active site configurations. The structures also show a stable, well-packed binding interface between the helices H4 of the two monomers, which is believed to be crucial for EmrE dimerization. Guided by the atomic details of this interface, we design proteolysis-resistant stapled peptides that bind to helix H4 of an EmrE monomer. The peptides are expected to interfere with the dimerization and thereby inhibit drug transport. Optimal positions of the peptide staple were determined using free-energy simulations of peptide binding to monomeric EmrE Three of the four top-scoring peptides selected for experimental testing resulted in significant inhibition of proton-driven ethidium efflux in live cells without nonspecific toxicity. The approach described here is expected to be of general use for the design of peptide therapeutics.}, } @article {pmid30082383, year = {2018}, author = {Quick, M and Abramyan, AM and Wiriyasermkul, P and Weinstein, H and Shi, L and Javitch, JA}, title = {The LeuT-fold neurotransmitter:sodium symporter MhsT has two substrate sites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7924-E7931}, pmid = {30082383}, issn = {1091-6490}, support = {P01 DA012408/DA/NIDA NIH HHS/United States ; R01 DA041510/DA/NIDA NIH HHS/United States ; U54 GM087519/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry ; Crystallography, X-Ray ; Humans ; Lactococcus lactis/*chemistry ; Protein Domains ; Symporters/*chemistry ; }, abstract = {Crystal structures of the neurotransmitter:sodium symporter MhsT revealed occluded inward-facing states with one substrate (Trp) bound in the primary substrate (S1) site and a collapsed extracellular vestibule, which in LeuT contains the second substrate (S2) site. In n-dodecyl-β-d-maltoside, the detergent used to prepare MhsT for crystallization, the substrate-to-protein binding stoichiometry was determined by using scintillation proximity to be 1 Trp:MhsT. Here, using the same experimental approach, as well as equilibrium dialysis, we report that in n-decyl-β-d-maltoside, or after reconstitution in lipid, MhsT, like LeuT, can simultaneously bind two Trp substrate molecules. Trp binding to the S2 site sterically blocks access to a substituted Cys at position 33 in the S2 site, as well as access to the deeper S1 site. Mutation of either the S1 or S2 site disrupts transport, consistent with previous studies in LeuT showing that substrate binding to the S2 site is an essential component of the transport mechanism.}, } @article {pmid30082382, year = {2018}, author = {Shi, F and Pei, A and Boyle, DT and Xie, J and Yu, X and Zhang, X and Cui, Y}, title = {Lithium metal stripping beneath the solid electrolyte interphase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8529-8534}, pmid = {30082382}, issn = {1091-6490}, abstract = {Lithium stripping is a crucial process coupled with lithium deposition during the cycling of Li metal batteries. Lithium deposition has been widely studied, whereas stripping as a subsurface process has rarely been investigated. Here we reveal the fundamental mechanism of stripping on lithium by visualizing the interface between stripped lithium and the solid electrolyte interphase (SEI). We observed nanovoids formed between lithium and the SEI layer after stripping, which are attributed to the accumulation of lithium metal vacancies. High-rate dissolution of lithium causes vigorous growth and subsequent aggregation of voids, followed by the collapse of the SEI layer, i.e., pitting. We systematically measured the lithium polarization behavior during stripping and find that the lithium cation diffusion through the SEI layer is the rate-determining step. Nonuniform sites on typical lithium surfaces, such as grain boundaries and slip lines, greatly accelerated the local dissolution of lithium. The deeper understanding of this buried interface stripping process provides beneficial clues for future lithium anode and electrolyte design.}, } @article {pmid30082381, year = {2018}, author = {}, title = {Correction for Burdyga et al., Phosphatases control PKA-dependent functional microdomains at the outer mitochondrial membrane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7882}, doi = {10.1073/pnas.1812383115}, pmid = {30082381}, issn = {1091-6490}, support = {PG/15/5/31110//British Heart Foundation/United Kingdom ; RG/12/3/29423//British Heart Foundation/United Kingdom ; }, } @article {pmid30082380, year = {2018}, author = {Lin, M and Zhang, X and Li, M and Xu, Y and Zhang, Z and Tao, J and Su, B and Liu, L and Shen, Y and Thiemens, MH}, title = {Five-S-isotope evidence of two distinct mass-independent sulfur isotope effects and implications for the modern and Archean atmospheres.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8541-8546}, pmid = {30082380}, issn = {1091-6490}, abstract = {The signature of mass-independent fractionation of quadruple sulfur stable isotopes (S-MIF) in Archean rocks, ice cores, and Martian meteorites provides a unique probe of the oxygen and sulfur cycles in the terrestrial and Martian paleoatmospheres. Its mechanistic origin, however, contains some uncertainties. Even for the modern atmosphere, the primary mechanism responsible for the S-MIF observed in nearly all tropospheric sulfates has not been identified. Here we present high-sensitivity measurements of a fifth sulfur isotope, stratospherically produced radiosulfur, along with all four stable sulfur isotopes in the same sulfate aerosols and a suite of chemical species to define sources and mechanisms on a field observational basis. The five-sulfur-isotope and multiple chemical species analysis approach provides strong evidence that S-MIF signatures in tropospheric sulfates are concomitantly affected by two distinct processes: an altitude-dependent positive 33S anomaly, likely linked to stratospheric SO2 photolysis, and a negative 36S anomaly mainly associated with combustion. Our quadruple stable sulfur isotopic measurements in varying coal samples (formed in the Carboniferous, Permian, and Triassic periods) and in SO2 emitted from combustion display normal 33S and 36S, indicating that the observed negative 36S anomalies originate from a previously unknown S-MIF mechanism during combustion (likely recombination reactions) instead of coal itself. The basic chemical physics of S-MIF in both photolytic and thermal reactions and their interplay, which were not explored together in the past, may be another ingredient for providing deeper understanding of the evolution of Earth's atmosphere and life's origin.}, } @article {pmid30082379, year = {2018}, author = {Robertson, EP and Fletcher, RJ and Cattau, CE and Udell, BJ and Reichert, BE and Austin, JD and Valle, D}, title = {Isolating the roles of movement and reproduction on effective connectivity alters conservation priorities for an endangered bird.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8591-8596}, pmid = {30082379}, issn = {1091-6490}, mesh = {Animal Migration/*physiology ; Animals ; *Endangered Species ; Falconiformes/*physiology ; Female ; Male ; *Models, Biological ; Reproduction/*physiology ; }, abstract = {Movement is important for ecological and evolutionary theory as well as connectivity conservation, which is increasingly critical for species responding to environmental change. Key ecological and evolutionary outcomes of movement, such as population growth and gene flow, require effective dispersal: movement that is followed by successful reproduction. However, the relative roles of movement and postmovement reproduction for effective dispersal and connectivity remain unclear. Here we isolate the contributions of movement and immigrant reproduction to effective dispersal and connectivity across the entire breeding range of an endangered raptor, the snail kite (Rostrhamus sociabilis plumbeus). To do so, we unite mark-resight data on movement and reproduction across 9 years and 27 breeding patches with an integrated model that decomposes effective dispersal into its hierarchical levels of movement, postmovement breeding attempt, and postmovement reproductive success. We found that immigrant reproduction limits effective dispersal more than movement for this endangered species, demonstrating that even highly mobile species may have limited effective connectivity due to reduced immigrant reproduction. We found different environmental limitations for the reproductive component of effective dispersal compared with movement, indicating that different conservation strategies may be needed when promoting effective dispersal rather than movement alone. We also demonstrate that considering immigrant reproduction, rather than movement alone, alters which patches are the most essential for connectivity, thereby changing conservation priorities. These results challenge the assumption that understanding movement alone is sufficient to infer connectivity and highlight that connectivity conservation may require not only fostering movement but also successful reproduction of immigrants.}, } @article {pmid30082378, year = {2018}, author = {Shepherd, AJ and Mickle, AD and Golden, JP and Mack, MR and Halabi, CM and de Kloet, AD and Samineni, VK and Kim, BS and Krause, EG and Gereau, RW and Mohapatra, DP}, title = {Macrophage angiotensin II type 2 receptor triggers neuropathic pain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8057-E8066}, pmid = {30082378}, issn = {1091-6490}, support = {P30 DK056341/DK/NIDDK NIH HHS/United States ; R01 NS042595/NS/NINDS NIH HHS/United States ; K99 HL125805/HL/NHLBI NIH HHS/United States ; R01 NS069898/NS/NINDS NIH HHS/United States ; F31 CA171927/CA/NCI NIH HHS/United States ; R00 HL125805/HL/NHLBI NIH HHS/United States ; }, mesh = {Allografts ; Animals ; Chronic Pain/genetics/*metabolism/pathology ; Hematopoietic Stem Cell Transplantation ; Macrophages/*metabolism/pathology ; Mice ; Neuralgia/genetics/*metabolism/pathology ; Receptor, Angiotensin, Type 2/genetics/*metabolism ; }, abstract = {Peripheral nerve damage initiates a complex series of structural and cellular processes that culminate in chronic neuropathic pain. The recent success of a type 2 angiotensin II (Ang II) receptor (AT2R) antagonist in a phase II clinical trial for the treatment of postherpetic neuralgia suggests angiotensin signaling is involved in neuropathic pain. However, transcriptome analysis indicates a lack of AT2R gene (Agtr2) expression in human and rodent sensory ganglia, raising questions regarding the tissue/cell target underlying the analgesic effect of AT2R antagonism. We show that selective antagonism of AT2R attenuates neuropathic but not inflammatory mechanical and cold pain hypersensitivity behaviors in mice. Agtr2-expressing macrophages (MΦs) constitute the predominant immune cells that infiltrate the site of nerve injury. Interestingly, neuropathic mechanical and cold pain hypersensitivity can be attenuated by chemogenetic depletion of peripheral MΦs and AT2R-null hematopoietic cell transplantation. Our study identifies AT2R on peripheral MΦs as a critical trigger for pain sensitization at the site of nerve injury, and therefore proposes a translatable peripheral mechanism underlying chronic neuropathic pain.}, } @article {pmid30082377, year = {2018}, author = {O'Connell, JF and Allen, J and Williams, MAJ and Williams, AN and Turney, CSM and Spooner, NA and Kamminga, J and Brown, G and Cooper, A}, title = {When did Homo sapiens first reach Southeast Asia and Sahul?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8482-8490}, pmid = {30082377}, issn = {1091-6490}, mesh = {Africa ; Archaeology ; Asia ; History, Ancient ; Human Migration/*history ; Humans ; }, abstract = {Anatomically modern humans (Homo sapiens, AMH) began spreading across Eurasia from Africa and adjacent Southwest Asia about 50,000-55,000 years ago (ca 50-55 ka). Some have argued that human genetic, fossil, and archaeological data indicate one or more prior dispersals, possibly as early as 120 ka. A recently reported age estimate of 65 ka for Madjedbebe, an archaeological site in northern Sahul (Pleistocene Australia-New Guinea), if correct, offers what might be the strongest support yet presented for a pre-55-ka African AMH exodus. We review evidence for AMH arrival on an arc spanning South China through Sahul and then evaluate data from Madjedbebe. We find that an age estimate of >50 ka for this site is unlikely to be valid. While AMH may have moved far beyond Africa well before 50-55 ka, data from the region of interest offered in support of this idea are not compelling.}, } @article {pmid30082147, year = {2018}, author = {Delves, MJ and Angrisano, F and Blagborough, AM}, title = {Antimalarial Transmission-Blocking Interventions: Past, Present, and Future.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {735-746}, doi = {10.1016/j.pt.2018.07.001}, pmid = {30082147}, issn = {1471-5007}, support = {MR/N00227X/1//Medical Research Council/United Kingdom ; }, abstract = {Malaria remains a major global health challenge. Appropriate use of current antimalarial tools has reduced the disease burden, but morbidity and mortality remain unacceptably high. It is widely accepted that, to achieve long-term control/eradication, it will be necessary to use interventions that inhibit the transmission of parasites to mosquitoes - these tools are termed transmission-blocking interventions (TBIs). This article aims to outline the rationale for the development of TBIs, with a focus on transmission-blocking drugs and (parasite-derived) transmission-blocking vaccines. We describe and summarise the current status of each of these intervention classes and attempt to identify future requirements in development, with a focus on the challenges of establishing each method within an integrated malarial control programme in the future.}, } @article {pmid30081966, year = {2018}, author = {Wagnew, F and Eshetie, S and Kibret, GD and Zegeye, A and Dessie, G and Mulugeta, H and Alemu, A}, title = {Diabetic nephropathy and hypertension in diabetes patients of sub-Saharan countries: a systematic review and meta-analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {565}, pmid = {30081966}, issn = {1756-0500}, mesh = {Africa South of the Sahara ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/complications ; Diabetic Nephropathies/*complications ; Humans ; Hypertension/*complications ; }, abstract = {OBJECTIVE: This meta-analysis was undertaken to estimate the prevalence of diabetic nephropathy and its association with hypertension in diabetics of sub-Saharan African countries.

RESULTS: A total of 27 studies were included for the meta-analysis. The pooled overall prevalence of diabetic nephropathy was 35.3 (95% CI 27.46-43.14). In sub-group analyses by types of diabetes and regions, for instance, the prevalence was 41.4% (95% CI 32.2-50.58%) in type-2 diabetes mellitus and 29.7% (95% CI 14.3-45.1%) in Eastern Africa. Pooled point estimates from included studies revealed an increased risk of diabetic nephropathy with hypertension compared to without hypertension (OR = 1.67, 95% CI 1.31, 2.14). Diabetic nephropathy is a common complication in diabetic patients. Diabetic nephropathy complication is significantly higher in hypertensive patients. A preventive strategy should be adopted or planned to reduce diabetes mellitus and its complication of neuropathy, particularly in hypertensive.}, } @article {pmid30081965, year = {2018}, author = {Zalucki, O and Harkins, D and Harris, L and Burne, THJ and Gronostajski, RM and Piper, M}, title = {Analysis of hippocampal-dependent learning and memory behaviour in mice lacking Nfix from adult neural stem cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {564}, pmid = {30081965}, issn = {1756-0500}, support = {DP160100368//Australian Research Council/ ; DP180100017//Australian Research Council/ ; }, mesh = {Animals ; Female ; Hippocampus/*physiology ; *Learning ; Male ; *Memory ; Mice ; Mice, Inbred C57BL ; NFI Transcription Factors/*genetics ; Neural Stem Cells ; }, abstract = {OBJECTIVE: The active place avoidance task (APA) is a behavioural task used to assess learning and memory in rodents. This task relies on the hippocampus, a region of the cerebral cortex capable of generating new neurons from neural stem cells. In this study, to gain further insight into the behavioural phenotype of mice deficient in the transcription factor Nfix, a gene expressed by adult neural stem cells, we examined learning and memory parameters from the APA task that were not published in our original investigation. We analysed time to first and second shock, maximum path and time of shock avoidance, number of entries into the shock zone and time spent in the shock zone. We also assessed performance in the APA task based on sex.

RESULTS: We found mice deficient in Nfix displayed decreased latency to second shock compared to the control mice. Nfix deficient mice entered the shock zone more frequently and also spent more time in the shock zone. Our data provides further insights into the memory deficits evident in Nfix mutant mice, indicating these mice have a memory retrieval problem and may employ a different navigation strategy in the APA task.}, } @article {pmid30081956, year = {2018}, author = {Mayala, HA and Bakari, KH and Mghanga, FP and ZhaoHui, W}, title = {Clinical significance of PET-CT coronary flow reserve in diagnosis of non-obstructive coronary artery disease.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {566}, pmid = {30081956}, issn = {1756-0500}, mesh = {Adult ; Coronary Angiography ; Coronary Artery Disease/*diagnostic imaging ; Coronary Circulation ; Female ; Humans ; Male ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Young Adult ; }, abstract = {OBJECTIVE: To improve current knowledge of coronary flow reserve and non-obstructive coronary artery disease in terms of definition, features and clinical implications of measurement of coronary flow reserve (CFR), is an integrated measure of focal, diffuse, and small vessel coronary artery disease, can also be explained as a calculated ratio of hyperaemic to rest absolute myocardial blood flow. Non-obstructive coronary artery disease is defined as atherosclerotic plaque that does not obstruct blood flow or result in anginal symptoms. We also aimed at knowing the significance of PET in diagnosing coronary microvascular disease.

RESULTS: In our study 92% were between 41 and 60 years. 83% were males and 17% females, more patients had hypertension about 50%, few had diabetes mellitus about 16%, while those with both hypertension and diabetes mellitus were 17%. About 83% had ST segment and T wave changes on ECG. All patients and controls had normal coronaries on coronary angiography TIMI 3 flow. On further investigation by Positron emission tomography/CT we found out 58% had abnormal CFR and 42% had normal coronary flow reserve. Our findings indicate PET/CT coronary flow reserve concept provides a platform for the diagnosis of non-obstructive coronary artery disease in patients with signs and symptoms of ischemia without angiographic obstructive CAD.}, } @article {pmid30081954, year = {2018}, author = {Chane, Y and Hailu, G and Kumera, G}, title = {Pension beneficiaries' household food insecurity and associated factors in Debre Markos town, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {561}, pmid = {30081954}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Ethiopia ; *Family Characteristics ; Female ; *Food Supply ; Humans ; Male ; Middle Aged ; Pensions ; Socioeconomic Factors ; Young Adult ; }, abstract = {OBJECTIVES: A community based cross-sectional study was conducted from March to April, 2016 in Debre Markos town, Northwest Ethiopia to assess the level of household food insecurity and associated factors among pension beneficiaries.

RESULTS: The overall prevalence of household food insecurity among pension beneficiaries' households was 82.5%. Among food insecure households, 4.9% were labelled as mildly, 48.5% moderately and 46.6% severely food insecure. Living in rental house (P = 0.05), being younger beneficiaries (P = 0.001), low monthly household income (P = 0.001) and poor self-reported health status (P = 0.03) were found significantly associated with household food insecurity. In conclusion, food insecurity was a public health problem among pension beneficiaries in the study area. The effort of the government to increase the pension benefit and making especial subsidy on food and health costs yield a long-term solution.}, } @article {pmid30081953, year = {2018}, author = {Zhu, J and Liao, M and Yao, Z and Liang, W and Li, Q and Liu, J and Yang, H and Ji, Y and Wei, W and Tan, A and Liang, S and Chen, Y and Lin, H and Zhu, X and Huang, S and Tian, J and Tang, R and Wang, Q and Mo, Z}, title = {Breast cancer in postmenopausal women is associated with an altered gut metagenome.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {136}, pmid = {30081953}, issn = {2049-2618}, mesh = {Adult ; Bacteria/*classification/genetics ; Bacterial Proteins/genetics ; Breast Neoplasms/metabolism/*microbiology ; C-Reactive Protein/metabolism ; Case-Control Studies ; Estradiol/metabolism ; Female ; *Gastrointestinal Microbiome ; Gene Regulatory Networks ; Humans ; Metagenomics/*methods ; Middle Aged ; Phylogeny ; Postmenopause/metabolism ; Premenopause/metabolism ; }, abstract = {BACKGROUND: Increasing evidence suggests that gut microbiota play a role in the pathogenesis of breast cancer. The composition and functional capacity of gut microbiota associated with breast cancer have not been studied systematically.

METHODS: We performed a comprehensive shotgun metagenomic analysis of 18 premenopausal breast cancer patients, 25 premenopausal healthy controls, 44 postmenopausal breast cancer patients, and 46 postmenopausal healthy controls.

RESULTS: Microbial diversity was higher in breast cancer patients than in controls. Relative species abundance in gut microbiota did not differ significantly between premenopausal breast cancer patients and premenopausal controls. In contrast, relative abundance of 45 species differed significantly between postmenopausal patients and postmenopausal controls: 38 species were enriched in postmenopausal patients, including Escherichia coli, Klebsiella sp_1_1_55, Prevotella amnii, Enterococcus gallinarum, Actinomyces sp. HPA0247, Shewanella putrefaciens, and Erwinia amylovora, and 7 species were less abundant in postmenopausal patients, including Eubacterium eligens and Lactobacillus vaginalis. Acinetobacter radioresistens and Enterococcus gallinarum were positively but weakly associated with expression of high-sensitivity C-reactive protein; Shewanella putrefaciens and Erwinia amylovora were positively but weakly associated with estradiol levels. Actinomyces sp. HPA0247 negatively but weakly correlated with CD3+CD8+ T cell numbers. Further characterization of metagenome functional capacity indicated that the gut metagenomes of postmenopausal breast cancer patients were enriched in genes encoding lipopolysaccharide biosynthesis, iron complex transport system, PTS system, secretion system, and beta-oxidation.

CONCLUSION: The composition and functions of the gut microbial community differ between postmenopausal breast cancer patients and healthy controls. The gut microbiota may regulate or respond to host immunity and metabolic balance. Thus, while cause and effect cannot be determined, there is a reproducible change in the microbiota of treatment-naive patients relative to matched controls.}, } @article {pmid30081949, year = {2018}, author = {Montassier, E and Al-Ghalith, GA and Hillmann, B and Viskocil, K and Kabage, AJ and McKinlay, CE and Sadowsky, MJ and Khoruts, A and Knights, D}, title = {CLOUD: a non-parametric detection test for microbiome outliers.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {137}, pmid = {30081949}, issn = {2049-2618}, mesh = {Bacteria/*classification ; Clostridium Infections/microbiology/*therapy ; Clostridium difficile/pathogenicity ; Computational Biology/*methods ; Dysbiosis/*diagnosis ; Enterocolitis/microbiology/*therapy ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Humans ; }, abstract = {BACKGROUND: Dysbiosis of the human gut microbiome is defined as a maladaptive or clinically relevant deviation of the community profile from the healthy or normal state. Dysbiosis has been implicated in an extensive set of metabolic, auto-immune, and infectious diseases, and yet there is substantial inter-individual variation in microbiome composition even within body sites of healthy humans. An individual's microbiome varies over time in a high-dimensional space to form their personal microbiome cloud. This cloud may or may not be similar to that of other people, both in terms of the average microbiome profile (conformity) and the diameter of the cloud (stability). However, there is currently no robust non-parametric test that determines whether a patient's microbiome cloud is an outlier with respect to a reference group of healthy individuals with widely varying microbiome profiles.

METHODS: Here, we propose a test for outliers' detection in the human gut microbiome that accounts for the wide range of microbiome phenotypes observed in a typical set of healthy individuals and for intra-individual temporal variation. Our robust nonparametric outlier detection test, the CLOUD test, performs two assessments of a patient's microbiome health: conformity, the extent to which the patient's microbiome cloud is ecologically similar to a subset of healthy subjects; and stability, which compares the cloud diameter of a patient to those of healthy subjects. The CLOUD test is based on locally linear embedded ecological distances, allowing it to account for widely varying microbiome compositions among reference individuals. It also leverages temporal variability within patients and reference individuals to increase the robustness of the test.

RESULTS: We describe the CLOUD test, and we apply it to one novel and two previously published cohorts of patients receiving fecal microbiota transplantation for recurrent Clostridium difficile colitis, as well as to two known healthy cohorts, demonstrating high concordance of the CLOUD conformity and stability indices with clinical outcomes.

CONCLUSIONS: Although the CLOUD test is not, on its own, a test for clinical dysbiosis, it nonetheless provides a framework for outlier testing that could be incorporated into evaluation of suspected dysbiosis, which may play a role in diagnosis and prognosis of numerous pediatric and adult diseases.}, } @article {pmid30081946, year = {2018}, author = {Weldemariam, S and Damte, A and Endris, K and Palcon, MC and Tesfay, K and Berhe, A and Araya, T and Hagos, H and Gebrehiwot, H}, title = {Late antenatal care initiation: the case of public health centers in Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {562}, pmid = {30081946}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Ethiopia ; Female ; *Health Facilities ; Humans ; Pregnancy ; *Prenatal Care ; *Public Health ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to determine the magnitude of late initiation of antenatal care visit and associated factors among antenatal care follow up women in Tselemte district health facilities. The data were obtained at health facilities level in a single survey within 1 month and there is no continuation part of this study or previously published part elsewhere.

RESULTS: 60.5% of women were late to initiate the first antenatal care visit. Time constraint with household activity (24.4%), distance to health center (17.2%) and fear of long waiting time in health facility (19.5%) were among the reasons mentioned for late initiation of antenatal care visit. Monthly income ≤ $21(400 ETB) (AOR = 4.54, 95% CI 1.07, 19.33), women who accompanied by their husband during antenatal care visit (AOR = 6.99, 95% CI 2.82, 17.31), who had information access on antenatal care (AOR = 4.85, 95% CI 1.88, 12.50) and distance from home to health center (AOR = 5.44, 95% CI 1.54, 19.25) were significantly associated factors with late initiation of antenatal care visit. This study illustrated that large number of pregnant women still late for first antenatal care visit. Husband involvement and health education about the timing of antenatal care initiation should be encouraged in all aspects of maternal care.}, } @article {pmid30081941, year = {2018}, author = {Ferrante, JA and Giles, MR and Benzie, E and Hunter, ME}, title = {A novel technique for isolating DNA from Tempus™ blood RNA tubes after RNA isolation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {563}, pmid = {30081941}, issn = {1756-0500}, mesh = {Animals ; DNA/*isolation & purification ; Deer ; RNA ; }, abstract = {OBJECTIVE: We use Tempus blood RNA tubes (Applied Biosystems) during health assessments of American moose (Alces alces spp.) as a minimally invasive means to obtain RNA. Here we describe a novel protocol to additionally isolate high-quality DNA from the supernatant remaining after the RNA isolation methodology. Metrics used to qualify DNA quality included measuring the concentration, obtaining a DNA integrity number from a genomic DNA ScreenTape assay (Agilent), and running the isolated DNA on an agarose gel.

RESULTS: Of the 23 samples analyzed, the average DNA concentration was 121 ng/µl (range 4-337 ng/µl) and a genomic DNA ScreenTape assay of seven samples indicated high DNA integrity values for 6 of the 7 samples (range 9.1-9.4 out of 10). Of the DNA sent for genotyping by sequencing, all proved to be of sufficient integrity to yield high-quality next-generation sequence results. We recommend this simple procedure to maximize the yield of both RNA and DNA from blood samples.}, } @article {pmid30081912, year = {2018}, author = {Esghaei, M and Daliri, MR and Treue, S}, title = {Attention decouples action potentials from the phase of local field potentials in macaque visual cortical area MT.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {86}, pmid = {30081912}, issn = {1741-7007}, abstract = {BACKGROUND: The timing of action potentials ("spikes") of cortical neurons has been shown to be aligned to the phase of low-frequency (< 10 Hz) local field potentials (LFPs) in several cortical areas. However, across the areas, this alignment varies and the role of this spike-phase coupling (SPC) in cognitive functions is not well understood.

RESULTS: Here, we propose a role in the coordination of neural activity by selective attention. After refining previous analytical methods for measuring SPC, we show that first, SPC is present along the dorsal processing pathway in macaque visual cortex (area MT); second, spikes occur in falling phases of the low-frequency LFP independent of the location of spatial attention; third, switching spatial attention into the receptive field (RF) of MT neurons decreases this coupling; and finally, the LFP phase causally influences the spikes.

CONCLUSIONS: Here, we show that spikes are coupled to the phase of low-frequency LFP along the dorsal visual pathway. Our data suggest that attention harnesses this spike-LFP coupling to de-synchronize neurons and thereby enhance the neural representation of the attended stimuli.}, } @article {pmid30081841, year = {2018}, author = {Mota, APZ and Vidigal, B and Danchin, EGJ and Togawa, RC and Leal-Bertioli, SCM and Bertioli, DJ and Araujo, ACG and Brasileiro, ACM and Guimaraes, PM}, title = {Comparative root transcriptome of wild Arachis reveals NBS-LRR genes related to nematode resistance.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {159}, pmid = {30081841}, issn = {1471-2229}, abstract = {BACKGROUND: The Root-Knot Nematode (RKN), Meloidogyne arenaria, significantly reduces peanut grain quality and yield worldwide. Whilst the cultivated species has low levels of resistance to RKN and other pests and diseases, peanut wild relatives (Arachis spp.) show rich genetic diversity and harbor high levels of resistance to many pathogens and environmental constraints. Comparative transcriptome analysis can be applied to identify candidate resistance genes.

RESULTS: Transcriptome analysis during the early stages of RKN infection of two peanut wild relatives, the highly RKN resistant Arachis stenosperma and the moderately susceptible A. duranensis, revealed genes related to plant immunity with contrasting expression profiles. These included genes involved in hormone signaling and secondary metabolites production and also members of the NBS-LRR class of plant disease resistance (R) genes. From 345 NBS-LRRs identified in A.duranensis reference genome, 52 were differentially expressed between inoculated and control samples, with the majority occurring in physical clusters unevenly distributed on eight chromosomes with preferential tandem duplication. The majority of these NBS-LRR genes showed contrasting expression behaviour between A. duranensis and A. stenosperma, particularly at 6 days after nematode inoculation, coinciding with the onset of the Hypersensitive Response in the resistant species. The physical clustering of some of these NBS-LRR genes correlated with their expression patterns in the contrasting genotypes. Four NBS-LRR genes exclusively expressed in A. stenosperma are located within clusters on chromosome Aradu. A09, which harbors a QTL for RKN resistance, suggesting a functional role for their physical arrangement and their potential involvement in this defense response.

CONCLUSION: The identification of functional novel R genes in wild Arachis species responsible for triggering effective defense cascades can contribute to the crop genetic improvement and enhance peanut resilience to RKN.}, } @article {pmid30081835, year = {2018}, author = {Bick, JT and Flöter, VL and Robinson, MD and Bauersachs, S and Ulbrich, SE}, title = {Small RNA-seq analysis of single porcine blastocysts revealed that maternal estradiol-17beta exposure does not affect miRNA isoform (isomiR) expression.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {590}, pmid = {30081835}, issn = {1471-2164}, mesh = {Animals ; Blastocyst/*chemistry/drug effects ; Estradiol/*adverse effects ; Female ; Gene Expression Profiling/veterinary ; Gene Expression Regulation, Developmental/drug effects ; Male ; Maternal Exposure/*adverse effects ; MicroRNAs/*genetics ; Molecular Sequence Annotation ; Organ Specificity ; RNA Isoforms/genetics ; Sequence Analysis, RNA/*veterinary ; Sex Factors ; Swine ; }, abstract = {BACKGROUND: The expression of microRNAs (miRNAs) is essential for the proper development of the mammalian embryo. A maternal exposure to endocrine disrupting chemicals during preimplantation bears the potential for transgenerational inheritance of disease through the epigenetic perturbation of the developing embryo. A comprehensive assembly of embryo-specific miRNAs and respective isoforms (isomiR) is lacking to date. We aimed at revealing the sex-specific miRNA expression profile of single porcine blastocysts developing in gilts orally exposed to exogenous estradiol-17 (E2). Therefore we analyzed the miRNA profile specifically focusing on isomiRs and potentially embryo-specific miRNAs.

RESULTS: Deep sequencing of small RNA (small RNA-seq) result in the detection of miRNA sequences mapping to known and predicted porcine miRNAs as well as novel miRNAs highly conserved in human and cattle. A set of highly abundant miRNAs and a large number of rarely expressed miRNAs were identified by using a small RNA analysis pipeline, which was integrated into a novel Galaxy workflow specifically benefits incompletely annotated species. In particular, orthologue species information increased the total number of annotated miRNAs, while mapping to other non-coding RNAs avoided falsely annotated miRNAs. Neither the low nor the high dose of E2 treatment (10 and 1000 µ E2/kg body weight daily, respectively) affected the miRNA profile in blastocysts despite the distinct differential mRNA expression and DNA methylation found in previous studies. The high number of generated sequence reads enabled a comprehensive analysis of the isomiR repertoire showing various templated and non-templated modifications. Furthermore, potentially blastocyst-specific miRNAs were identified.

CONCLUSIONS: In pre-implantation embryos, numerous distinct isomiRs were discovered indicating a high complexity of miRNA expression. Neither the sex of the embryo nor a maternal E2 exposure affected the miRNA expression profile of developing porcine blastocysts. The adaptation to the continuous duration of the E2 treatment might explain the lack of an effect.}, } @article {pmid30081834, year = {2018}, author = {Wu, J and Lin, L and Xu, M and Chen, P and Liu, D and Sun, Q and Ran, L and Wang, Y}, title = {Homoeolog expression bias and expression level dominance in resynthesized allopolyploid Brassica napus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {586}, pmid = {30081834}, issn = {1471-2164}, support = {31330057//National Nature Science Foundation of China/ ; 31601330//National Nature Science Foundation of China/ ; 2015CB150201//National Key Basic Research Program/ ; 2015M581867//China Postdoctoral Science Foundation/ ; 2016T90514//China Postdoctoral Science Foundation/ ; }, mesh = {Brassica napus/*genetics/metabolism ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant ; Plant Breeding ; Plant Proteins/*genetics ; Polyploidy ; Sequence Analysis, RNA/methods ; Whole Genome Sequencing/methods ; }, abstract = {BACKGROUND: Allopolyploids require rapid genetic and epigenetic modifications to reconcile two or more sets of divergent genomes. To better understand the fate of duplicate genes following genomic mergers and doubling during allopolyploid formation, in this study, we explored the global gene expression patterns in resynthesized allotetraploid Brassica napus (AACC) and its diploid parents B. rapa (AA) and B. oleracea (CC) using RNA sequencing of leaf transcriptomes.

RESULTS: We found that allopolyploid B. napus formation was accompanied by extensive changes (approximately one-third of the expressed genes) in the parental gene expression patterns ('transcriptome shock'). Interestingly, the majority (85%) of differentially expressed genes (DEGs) were downregulated in the allotetraploid. Moreover, the homoeolog expression bias (relative contribution of homoeologs to the transcriptome) and expression level dominance (total expression level of both homoeologs) were thoroughly investigated by monitoring the expression of 23,766 B. oleracea-B. rapa orthologous gene pairs. Approximately 36.5% of the expressed gene pairs displayed expression bias with a slight preference toward the A-genome. In addition, 39.6, 4.9 and 9.0% of the expressed gene pairs exhibited expression level dominance (ELD), additivity expression and transgressive expression, respectively. The genome-wide ELD was also biased toward the A-genome in the resynthesized B. napus. To explain the ELD phenomenon, we compared the individual homoeolog expression levels relative to those of the diploid parents and found that ELD in the direction of the higher-expression parent can be explained by the downregulation of homoeologs from the dominant parent or upregulation of homoeologs from the nondominant parent; however, ELD in the direction of the lower-expression parent can be explained only by the downregulation of the nondominant parent or both homoeologs. Furthermore, Gene Ontology (GO) enrichment analysis suggested that the alteration in the gene expression patterns could be a prominent cause of the phenotypic variation between the newly formed B. napus and its parental species.

CONCLUSIONS: Collectively, our data provide insight into the rapid repatterning of gene expression at the beginning of Brassica allopolyploidization and enhance our knowledge of allopolyploidization processes.}, } @article {pmid30081833, year = {2018}, author = {Yin, H and Guo, HB and Weston, DJ and Borland, AM and Ranjan, P and Abraham, PE and Jawdy, SS and Wachira, J and Tuskan, GA and Tschaplinski, TJ and Wullschleger, SD and Guo, H and Hettich, RL and Gross, SM and Wang, Z and Visel, A and Yang, X}, title = {Diel rewiring and positive selection of ancient plant proteins enabled evolution of CAM photosynthesis in Agave.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {588}, pmid = {30081833}, issn = {1471-2164}, support = {DE-SC0008834//Department of Energy, Office of Science, Genomic Science Program/ ; LDRD 5801//Oak Ridge National Laboratory/ ; }, mesh = {Agave/chemistry/*genetics/metabolism ; Carbon/*metabolism ; Carbon Cycle ; Evolution, Molecular ; Gene Expression Profiling ; Gene Regulatory Networks ; Genomics ; Models, Molecular ; Photosynthesis ; Phylogeny ; Plant Proteins/*chemistry/*genetics ; Protein Structure, Secondary ; }, abstract = {BACKGROUND: Crassulacean acid metabolism (CAM) enhances plant water-use efficiency through an inverse day/night pattern of stomatal closure/opening that facilitates nocturnal CO2 uptake. CAM has evolved independently in over 35 plant lineages, accounting for ~ 6% of all higher plants. Agave species are highly heat- and drought-tolerant, and have been domesticated as model CAM crops for beverage, fiber, and biofuel production in semi-arid and arid regions. However, the genomic basis of evolutionary innovation of CAM in genus Agave is largely unknown.

RESULTS: Using an approach that integrated genomics, gene co-expression networks, comparative genomics and protein structure analyses, we investigated the molecular evolution of CAM as exemplified in Agave. Comparative genomics analyses among C3, C4 and CAM species revealed that core metabolic components required for CAM have ancient genomic origins traceable to non-vascular plants while regulatory proteins required for diel re-programming of metabolism have a more recent origin shared among C3, C4 and CAM species. We showed that accelerated evolution of key functional domains in proteins responsible for primary metabolism and signaling, together with a diel re-programming of the transcription of genes involved in carbon fixation, carbohydrate processing, redox homeostasis, and circadian control is required for the evolution of CAM in Agave. Furthermore, we highlighted the potential candidates contributing to the adaptation of CAM functional modules.

CONCLUSIONS: This work provides evidence of adaptive evolution of CAM related pathways. We showed that the core metabolic components required for CAM are shared by non-vascular plants, but regulatory proteins involved in re-reprogramming of carbon fixation and metabolite transportation appeared more recently. We propose that the accelerated evolution of key proteins together with a diel re-programming of gene expression were required for CAM evolution from C3 ancestors in Agave.}, } @article {pmid30081831, year = {2018}, author = {Nakahama, K and Urata, N and Shinya, T and Hayashi, K and Nanto, K and Rosa, AC and Kawaoka, A}, title = {RNA-seq analysis of lignocellulose-related genes in hybrid Eucalyptus with contrasting wood basic density.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {156}, pmid = {30081831}, issn = {1471-2229}, abstract = {BACKGROUND: Wood basic density (WBD), the biomass of plant cell walls per unit volume, is an important trait for elite tree selection in kraft pulp production. Here, we investigated the correlation between WBD and wood volumes or wood properties using 98 open-pollinated, 2.4 to 2.8 year-old hybrid Eucalyptus (Eucalyptus urophylla x E. grandis). Transcript levels of lignocellulose biosynthesis-related genes were studied.

RESULTS: The progeny plants had average WBD of 516 kg/m3 with normal distribution and did not show any correlations between WBD and wood volume or components of α-cellulose, hemicellulose and Klason lignin content. Transcriptomic analysis of two groups of five plants each with high (570-609 kg/m3) or low (378-409 kg/m3) WBD was carried out by RNA-Seq analysis with total RNAs extracted from developing xylem tissues at a breast height. Lignocellulose biosynthesis-related genes, such as cellulose synthase, invertase, cinnamate-4-hydroxylase and cinnamoyl-CoA reductase showed higher transcript levels in the high WBD group. Among plant cell wall modifying genes, increased transcript levels of several expansin and xyloglucan endo-transglycosylase/hydrolase genes were also found in high WBD plants. Interestingly, strong transcript levels of several cytoskeleton genes encoding tubulin, actin and myosin were observed in high WBD plants. Furthermore, we also found elevated transcript levels of genes encoding NAC, MYB, basic helix-loop-helix, homeodomain, WRKY and LIM transcription factors in the high WBD plants. All these results indicate that the high WBD in plants has been associated with the increased transcription of many genes related to lignocellulose formation.

CONCLUSIONS: Most lignocellulose biosynthesis related genes exhibited a tendency to transcribe at relatively higher level in high WBD plants. These results suggest that lignocellulose biosynthesis-related genes may be associated with WBD.}, } @article {pmid30081830, year = {2018}, author = {Di Canito, A and Zampolli, J and Orro, A and D'Ursi, P and Milanesi, L and Sello, G and Steinbüchel, A and Di Gennaro, P}, title = {Genome-based analysis for the identification of genes involved in o-xylene degradation in Rhodococcus opacus R7.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {587}, pmid = {30081830}, issn = {1471-2164}, mesh = {Bacterial Proteins/*genetics/metabolism ; Biodegradation, Environmental ; Dioxygenases/genetics/metabolism ; Mixed Function Oxygenases/genetics/metabolism ; Multigene Family ; Rhodococcus/genetics/*growth & development/metabolism ; Whole Genome Sequencing/*methods ; Xylenes/*chemistry ; }, abstract = {BACKGROUND: Bacteria belonging to the Rhodococcus genus play an important role in the degradation of many contaminants, including methylbenzenes. These bacteria, widely distributed in the environment, are known to be a powerhouse of numerous degradation functions, due to their ability to metabolize a wide range of organic molecules including aliphatic, aromatic, polycyclic aromatic compounds (PAHs), phenols, and nitriles. In accordance with their immense catabolic diversity, Rhodococcus spp. possess large and complex genomes, which contain a multiplicity of catabolic genes, a high genetic redundancy of biosynthetic pathways and a sophisticated regulatory network. The present study aimed to identify genes involved in the o-xylene degradation in R. opacus strain R7 through a genome-based approach.

RESULTS: Using genome-based analysis we identified all the sequences in the R7 genome annotated as dioxygenases or monooxygenases/hydroxylases and clustered them into two different trees. The akb, phe and prm sequences were selected as genes encoding respectively for dioxygenases, phenol hydroxylases and monooxygenases and their putative involvement in o-xylene oxidation was evaluated. The involvement of the akb genes in o-xylene oxidation was demonstrated by RT-PCR/qPCR experiments after growth on o-xylene and by the selection of the R7-50 leaky mutant. Although the akb genes are specifically activated for o-xylene degradation, metabolic intermediates of the pathway suggested potential alternative oxidation steps, possibly through monooxygenation. This led us to further investigate the role of the prm and the phe genes. Results showed that these genes were transcribed in a constitutive manner, and that the activity of the Prm monooxygenase was able to transform o-xylene slowly in intermediates as 3,4-dimethylphenol and 2-methylbenzylalcohol. Moreover, the expression level of phe genes, homologous to the phe genes of Rhodococcus spp. 1CP and UPV-1 with a 90% identity, could explain their role in the further oxidation of o-xylene and R7 growth on dimethylphenols.

CONCLUSIONS: These results suggest that R7 strain is able to degrade o-xylene by the Akb dioxygenase system leading to the production of the corresponding dihydrodiol. Likewise, the redundancy of sequences encoding for several monooxygenases/phenol hydroxylases, supports the involvement of other oxygenases converging in the o-xylene degradation pathway in R7 strain.}, } @article {pmid30081829, year = {2018}, author = {Bhatta, M and Morgounov, A and Belamkar, V and Poland, J and Baenziger, PS}, title = {Unlocking the novel genetic diversity and population structure of synthetic Hexaploid wheat.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {591}, pmid = {30081829}, issn = {1471-2164}, support = {OPP1133199//Department for International Development/ ; 16-16-10005//Russian Science Support Foundation/ ; 2017-67007-25939//National Institute of Food and Agriculture/ ; 2011-68002-30029//USDA-AFRI/ ; 59-0790-4-092//U.S. Wheat and Barley Scab Initiative/ ; }, mesh = {Chromosome Mapping ; Genetics, Population ; Plant Breeding ; *Polymorphism, Single Nucleotide ; Polyploidy ; Sequence Analysis, DNA/*methods ; Triticum/*genetics ; }, abstract = {BACKGROUND: Synthetic hexaploid wheat (SHW) is a reconstitution of hexaploid wheat from its progenitors (Triticum turgidum ssp. durum L.; AABB x Aegilops tauschii Coss.; DD) and has novel sources of genetic diversity for broadening the genetic base of elite bread wheat (BW) germplasm (T. aestivum L). Understanding the diversity and population structure of SHWs will facilitate their use in wheat breeding programs. Our objectives were to understand the genetic diversity and population structure of SHWs and compare the genetic diversity of SHWs with elite BW cultivars and demonstrate the potential of SHWs to broaden the genetic base of modern wheat germplasm.

RESULTS: The genotyping-by-sequencing of SHW provided 35,939 high-quality single nucleotide polymorphisms (SNPs) that were distributed across the A (33%), B (36%), and D (31%) genomes. The percentage of SNPs on the D genome was nearly same as the other two genomes, unlike in BW cultivars where the D genome polymorphism is generally much lower than the A and B genomes. This indicates the presence of high variation in the D genome in the SHWs. The D genome gene diversity of SHWs was 88.2% higher than that found in a sample of elite BW cultivars. Population structure analysis revealed that SHWs could be separated into two subgroups, mainly differentiated by geographical location of durum parents and growth habit of the crop (spring and winter type). Further population structure analysis of durum and Ae. parents separately identified two subgroups, mainly based on type of parents used. Although Ae. tauschii parents were divided into two sub-species: Ae. tauschii ssp. tauschii and ssp. strangulate, they were not clearly distinguished in the diversity analysis outcome. Population differentiation between SHWs (Spring_SHW and Winter_SHW) samples using analysis of molecular variance indicated 17.43% of genetic variance between populations and the remainder within populations.

CONCLUSIONS: SHWs were diverse and had a clearly distinguished population structure identified through GBS-derived SNPs. The results of this study will provide valuable information for wheat genetic improvement through inclusion of novel genetic variation and is a prerequisite for association mapping and genomic selection to unravel economically important marker-trait associations and for cultivar development.}, } @article {pmid30081827, year = {2018}, author = {Cao, K and Yan, F and Xu, D and Ai, K and Yu, J and Bao, E and Zou, Z}, title = {Phytochrome B1-dependent control of SP5G transcription is the basis of the night break and red to far-red light ratio effects in tomato flowering.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {158}, pmid = {30081827}, issn = {1471-2229}, support = {2016BZ09//the study on key technologies for healthy production of efficient resources utilization in protected vegetables/ ; CX161002//research on key technologies and supporting equipment of protected vegetable production/ ; AA16380048//the achievement transformation of multilayer stereo water culture/ ; }, abstract = {BACKGROUND: Phytochromes are dimeric proteins with critical roles in perceiving day length and the environmental signals that trigger flowering. Night break (NB) and the red to far-red light ratio (R:FR) have been used extensively as tools to study the photoperiodic control of flowering. However, at the molecular level, little is known about the effect of NB and different R:FR values on flowering in day-neutral plants (DNPs) such as tomato.

RESULTS: Here, we show that tomato SP5G, SP5G2, and SP5G3 are homologs of Arabidopsis thaliana FLOWERING LOCUS T (FT) that repress flowering in Nicotiana benthamiana. NB every 2 h at intensities of 10 μmol m- 2 s- 1 or lower R:FR (e.g., 0.6) caused a clear delay in tomato flowering and promoted SP5G mRNA expression. The promoted SP5G mRNA expression induced by red light NB and low R:FR treatments was reversed by a subsequent FR light stimulus or a higher R:FR treatment. The tomato phyB1 mutation abolished the effects of NB and lower R:FR treatments on flowering and SP5G mRNA expression, indicating that the effects were mediated by phytochrome B1 in tomato.

CONCLUSION: Our results strongly suggest that SP5G mRNA suppression is the principal cause of NB and lower R:FR effects on flowering in tomato.}, } @article {pmid30081825, year = {2018}, author = {Bohlin, J and Eldholm, V and Brynildsrud, O and Petterson, JH and Alfsnes, K}, title = {Modeling of the GC content of the substituted bases in bacterial core genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {589}, pmid = {30081825}, issn = {1471-2164}, mesh = {Bacteria/*genetics ; *Base Composition ; Evolution, Molecular ; Genome, Bacterial ; Models, Genetic ; Models, Theoretical ; *Mutation ; }, abstract = {BACKGROUND: The purpose of the present study was to examine the GC content of substituted bases (sbGC) in the core genomes of 35 bacterial species. Each species, or core genome, constituted genomes from at least 10 strains. We also wanted to explore whether sbGC for each strain was associated with the corresponding species' core genome GC content (cgGC). We present a simple mathematical model that estimates sbGC from cgGC. The model assumes only that the estimated sbGC is a function of cgGC proportional to fixed AT→GC (α) and GC → AT (β) mutation rates. Non-linear regression was used to estimate parameters α and β from the empirical data described above.

RESULTS: We found that sbGC for each strain showed a non-linear association with the corresponding cgGC with a bias towards higher GC content for most core genomes (66.3% of the strains), assuming as a null-hypothesis that sbGC should be approximately equal to cgGC. The most GC rich core genomes (i.e. approximately %GC > 60), on the other hand, exhibited slightly less GC-biased sbGC than expected. The best fitted regression model indicates that GC → AT mutation rates β = (1.91 ± 0.13) p < 0.001 are approximately (1.91/0.79) = 2.42 times as high, on average, as AT→GC α = (- 0.79 ± 0.25) p < 0.001 mutation rates. Whether the observed sbGC GC-bias for all but the most GC-rich prokaryotic species is due to selection, compensating for the GC → AT mutation bias, and/or selective neutral processes is currently debated. Residual standard error was found to be σ = 0.076 indicating estimated errors of sbGC to be approximately within ±15.2% GC (95% confidence interval) for the strains of all species in the study.

CONCLUSION: Not only did our mathematical model give reasonable estimates of sbGC it also provides further support to previous observations that mutation rates in prokaryotes exhibit a universal GC → AT bias that appears to be remarkably consistent between taxa.}, } @article {pmid30081823, year = {2018}, author = {Zeng, L and Liu, X and Zhou, Z and Li, D and Zhao, X and Zhu, L and Luo, Y and Hu, S}, title = {Identification of a G2-like transcription factor, OsPHL3, functions as a negative regulator of flowering in rice by co-expression and reverse genetic analysis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {157}, pmid = {30081823}, issn = {1471-2229}, support = {31000561//The National Natural Science Foundation of China/ ; 31771473//The National Natural Science Foundation of China/ ; 2017140//Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; XDA08020102//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, abstract = {BACKGROUND: Flowering time is a key trait for regional adaption and seed production in rice (Oryza sativa L.). Forward and reverse genetic studies have characterized a number of flowering-time genes. However, co-expression analysis has not been used to identify the flowering-time genes.

RESULTS: We predicted a G2-like family transcription factor, OsPHL3, by co-expression networks analysis with photoperiodic flowering pathway genes. OsPHL3 contains a MYB-CC domain, and was localized in the nucleus with transcriptional activation potential. OsPHL3 was mainly expressed in the leaves and exhibited a circadian rhythmic expression pattern. Rice lines overexpressing OsPHL3 showed a delayed flowering time in the genetic background of TP309 under both long-day (Beijing) and short-day (Hainan) conditions. By contrast, the knockout rice lines of OsPHL3 by CRISPR/Cas9 technology promoted flowering time regardless of genetic backgrounds (i.e. Nipponbare and TP309) or day length. Further analysis indicated that OsPHL3 delayed flowering time by down-regulating the expression of Hd3a and RFT1 through promoting Hd1 under long-day conditions (LDs), or suppressing Ehd1/Hd1 under short-day conditions (SDs).

CONCLUSIONS: Our results suggested that co-expression analysis is a useful strategy for identifying novel flowering-time genes in rice.}, } @article {pmid30081821, year = {2018}, author = {Hamadeh, B and Chalak, L and Coppens d'Eeckenbrugge, G and Benoit, L and Joly, HI}, title = {Evolution of almond genetic diversity and farmer practices in Lebanon: impacts of the diffusion of a graft-propagated cultivar in a traditional system based on seed-propagation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {155}, pmid = {30081821}, issn = {1471-2229}, support = {09 E F6/L 24//French-Lebanese Program CEDRE/ ; }, abstract = {BACKGROUND: Under cultivation, many outcrossing fruit tree species have switched from sexual reproduction to vegetative propagation. Traditional production systems have persisted, where cultivar propagation is based on a mixed reproductive system. For millenia, almond, Prunus dulcis, has been propagated by seeds. Almond grafting remained of little importance until recently. In Lebanon, both sexual and clonal reproductions are used for almond propagation. We used 15 microsatellite markers to investigate the effect of introducing graft-propagated cultivars and associated practices, on the structure of the genetic diversity among and within the two main Lebanese cultivars.

RESULTS: As expected, the sexually propagated cultivar Khachabi exhibited more genotypic and genetic diversity than the vegetatively propagated cultivar Halwani. It also exhibited lower differentiation among populations. The distribution of clones showed that propagation modes were not exclusive: farmers have introduced clonal propagation in the seed-propagated cultivar while they have maintained a diversity of genotypes within populations that were mostly graft-propagated. These practices are also important to avoid mate limitations that hamper fruit production in a self-incompatible species. 'Khachabi' is structured into two gene pools separated by the Lebanese mountains. As to 'Halwani', two different gene pools were introduced. The most ancient one shares the same geographic range as 'Khachabi'; longtime coexistence and sexual reproduction have resulted in admixture with 'Khachabi'. In contrast, the more recent introduction of the second gene pool in the Bekaa region followed an evolution towards more extensive clonal propagation of 'Halwani' limiting hybridizations. Furthermore, some pairs of geographically distant 'Halwani' orchards, exhibited low genetic distances, suggesting that a network of exchanges between farmers was effective on a large scale and/or that farmers brought clonal plant material from a common source.

CONCLUSIONS: Almond diversification in Lebanon is clearly related to the evolution of propagation practices adapted to self-incompatible cultivars. The comparison between both cultivars demonstrated the genetic effects of the introduction of a new cultivar and the associated grafting propagation practices. Our study provided information to develop a strategy for in situ conservation of cultivars and to limit gene flow from introduced material to ancient orchards.}, } @article {pmid30081820, year = {2018}, author = {Michelotti, V and Lamontanara, A and Buriani, G and Orrù, L and Cellini, A and Donati, I and Vanneste, JL and Cattivelli, L and Tacconi, G and Spinelli, F}, title = {Comparative transcriptome analysis of the interaction between Actinidia chinensis var. chinensis and Pseudomonas syringae pv. actinidiae in absence and presence of acibenzolar-S-methyl.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {585}, pmid = {30081820}, issn = {1471-2164}, support = {613678//FP7 International Cooperation/ ; Interact D.M. 26045-5/12/2011//Ministero delle Politiche Agricole Alimentari e Forestali/ ; Ardica D.M. 27234/7303/2011//Ministero delle Politiche Agricole Alimentari e Forestali/ ; }, mesh = {Actinidia/drug effects/*genetics/microbiology ; Disease Resistance ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant/drug effects ; Gene Regulatory Networks/drug effects ; Plant Diseases/*genetics/microbiology ; Plant Proteins/*genetics ; Plant Roots/genetics/microbiology ; Pseudomonas syringae/physiology ; Sequence Analysis, RNA ; Thiadiazoles/*pharmacology ; }, abstract = {BACKGROUND: Since 2007, bacterial canker caused by Pseudomonas syringae pv. actinidiae (Psa) has become a pandemic disease leading to important economic losses in every country where kiwifruit is widely cultivated. Options for controlling this disease are very limited and rely primarily on the use of bactericidal compounds, such as copper, and resistance inducers. Among the latter, the most widely studied is acibenzolar-S-methyl. To elucidate the early molecular reaction of kiwifruit plants (Actinidia chinensis var. chinensis) to Psa infection and acibenzolar-S-methyl treatment, a RNA seq analysis was performed at different phases of the infection process, from the epiphytic phase to the endophytic invasion on acibenzolar-S-methyl treated and on non-treated plants. The infection process was monitored in vivo by confocal laser scanning microscopy.

RESULTS: De novo assembly of kiwifruit transcriptome revealed a total of 39,607 transcripts, of which 3360 were differentially expressed during the infection process, primarily 3 h post inoculation. The study revealed the coordinated changes of important gene functional categories such as signaling, hormonal balance and transcriptional regulation. Among the transcription factor families, AP2/ERF, MYB, Myc, bHLH, GATA, NAC, WRKY and GRAS were found differentially expressed in response to Psa infection and acibenzolar-S-methyl treatment. Finally, in plants treated with acibenzolar-S-methyl, a number of gene functions related to plant resistance, such as PR proteins, were modulated, suggesting the set-up of a more effective defense response against the pathogen. Weighted-gene coexpression network analysis confirmed these results.

CONCLUSIONS: Our work provides an in-depth description of the plant molecular reactions to Psa, it highlights the metabolic pathway related to acibenzolar-S-methyl-induced resistance and it contributes to the development of effective control strategies in open field.}, } @article {pmid30081819, year = {2018}, author = {Roy, A and George, S and Palli, SR}, title = {Correction to: Multiple functions of CREB-binding protein during postembryonic development: identification of target genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {584}, pmid = {30081819}, issn = {1471-2164}, abstract = {Following the publication of this article [1], the authors found that the primers listed for CREB-binding protein were not correct. This mistake occurred during assembly of the primer table and the authors apologize for this error. This correction does not change the data included in the paper, their interpretation nor the conclusions drawn.}, } @article {pmid30081817, year = {2018}, author = {Galeng-Lawilao, J and Kumar, A and De Waele, D}, title = {QTL mapping for resistance to and tolerance for the rice root-knot nematode, Meloidogyne graminicola.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {53}, pmid = {30081817}, issn = {1471-2156}, abstract = {BACKGROUND: The root-knot nematode Meloidogyne graminicola is an obligate biotrophic pathogen considered to be the most damaging nematode species that causes significant yield losses to upland and rainfed lowland rice production in South and Southeast Asia. Mapping and identification of quantitative trait loci (QTL) for resistance to and tolerance for M. graminicola may offer a safe and economic management option to farmers. In this study, resistance to and tolerance for M. graminicola in Asian rice (Oryza sativa L.) were studied in a mapping population consisting of 300 recombinant inbred lines (RILs) derived from IR78877-208-B-1-2, an aerobic rice genotype with improved resistance to and tolerance for M. graminicola, and IR64, a popular, high-yielding rice mega-variety susceptible to M. graminicola. RILs were phenotyped for resistance and tolerance in the dry seasons of 2012 and 2013. QTL analysis was performed using 131 single nucleotide polymorphism (SNP) and 33 simple sequence repeat (SSR) markers.

RESULTS: Three QTLs with main effects on chromosomes 4 (qMGR4.1), 7 (qMGR7.1) and 9 (qMGR9.1) and two epistatic interactions (qMGR3.1/ qMGR11.1 and qMGR4.2/ qMGR8.1) associated with nematode reproduction that were consistent in the two seasons were detected. A QTL affecting root galling was found on chromosomes 4 (qGR4.1) and 8 (qGR8.1), and QTLs for nematode tolerance were found on chromosomes 5 (qYR5.1) and 11 (qYR11.1). These QTLs were consistent in both seasons. A QTL for grain yield was found on chromosome 10 (qGYLD10.1), a QTL affecting filled grains per panicle was detected on chromosome 11 (qFG11.1) and a QTL for fresh root weight was found on chromosomes 2 (qFRWt2.1), 8 (qFRWt8.1) and 12 (qFRWt12.1) in both seasons. The donor of the alleles for qMGR4.1, qMGR7.1, qMGR9.1, qGR4.1, qGR8.1, qYR5.1 and qFRWt2.1 was IR78877-208-B-1-2, whereas for qYR11.1, qGYLD10.1 and qFG11.1, qFRWt8.1 and qFRWt12.1 was IR64. Lines having favorable alleles for resistance, tolerance and yield provided better yield under nematode-infested conditions and could be a starting point of marker-assisted breeding (MAB) for the improvement of M. graminicola resistance and tolerance in Asian rice.

CONCLUSION: This study identified a total of 12 QTLs with main effects and two epistatic interactions in the 1st season and 2nd season related to M. graminicola resistance and tolerance, and other agronomic traits such as plant yield, percentage of filled grains, and fresh and dry root weight. Rice genotypes that have the favorable alleles for resistance (qMGR4.1, qMGR7.1, qMGR9.1, qGR4.1, qGR8.1) and tolerance (qYR5.1, and qYR11.1,) QTLs, and which are either resistant or partially resistant and tolerant, were also selected. These selected genotypes and the identified QTLs are vital information in designing MAB for the improvement of high-yielding rice genotypes but are susceptible to M. graminicola infection.}, } @article {pmid30079107, year = {2018}, author = {Andrade, PP and da Silva Ferreira, MA and Muniz, MS and de Casto Lira-Neto, A}, title = {GM insect pests under the Brazilian regulatory framework: development and perspectives.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 8}, pages = {16}, pmid = {30079107}, issn = {1753-6561}, abstract = {The emergence of new technologies for genetic modification has broadened the range of possible new products. The regulations of many countries that could benefit from these new products may not be prepared to assess risks and enable science-based decision-making. This is especially acute in the case of genetically modified insects with potential use in public health and agriculture. Modifications of the regulatory framework, sometimes necessary to allow a proper risk assessment of products from new technologies, are strongly influenced by political decisions derived from the balance of power and interest among stakeholders. This article discusses the genesis of the Brazilian regulatory framework, its applicability for the risk assessment of genetically modified insects and the scenarios that have shaped the two biosafety laws that established the basis for the use of modern biotechnology in the country. It is concluded that, for the adoption of the new technologies, it is important to carefully navigate the political tensions by seeking the engagement and empowerment of stakeholders supporting science-based decision-making in order to gather the necessary support for adoption of risk assessment as the basis for final decisions, allowing the use of new technologies.}, } @article {pmid30079106, year = {2018}, author = {Stirling, A and Hayes, KR and Delborne, J}, title = {Towards inclusive social appraisal: risk, participation and democracy in governance of synthetic biology.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 8}, pages = {15}, pmid = {30079106}, issn = {1753-6561}, abstract = {Frameworks that govern the development and application of novel products, such as the products of synthetic biology, should involve all those who are interested or potentially affected by the products. The governance arrangements for novel products should also provide a democratic mechanism that allows affected parties to express their opinions on the direction that innovation does or does not take. In this paper we examine rationales, obstacles and opportunities for public participation in governance of novel synthetic biology products. Our analysis addresses issues such as uncertainties, the considering of alternative innovations, and broader social and environmental implications. The crucial issues in play go beyond safety alone, to include contending social values around diverse notions of benefit and harm. The paper highlights the need for more inclusive social appraisal mechanisms to inform governance of Synthetic Biology and alternative products, and discusses a few practical methods to help achieve this goal.}, } @article {pmid30079105, year = {2018}, author = {Ahuja, V}, title = {Regulation of emerging gene technologies in India.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 8}, pages = {14}, doi = {10.1186/s12919-018-0106-0}, pmid = {30079105}, issn = {1753-6561}, abstract = {In India, genetically modified organisms (GMOs) and the products thereof are regulated under the "Rules for the manufacture, use, import, export & storage of hazardous microorganisms, genetically engineered organisms or cells, 1989" (referred to as Rules, 1989) notified under the Environment (Protection) Act, 1986. These Rules are implemented by the Ministry of Environment, Forest and Climate Change, Department of Biotechnology and State Governments though six competent authorities. The Rules, 1989 are supported by series of guidelines on contained research, biologics, confined field trials, food safety assessment, environmental risk assessment etc. The definition of genetic engineering in the Rules, 1989 implies that new genome engineering technologies including gene editing and gene drives. May be covered under the rules. India is a signatory to the Cartagena Protocol on Biosafety (CPB), however, the definition of modern biotechnology, as in CPB is yet to be adopted in the national regulations. The regulatory authorities review and take into account the experience by other countries in dealing with new technologies. However, there is yet no clarity on how the emerging technologies will be dealt with in India, though research has been initiated in several leading institutions.}, } @article {pmid30079104, year = {2018}, author = {Turner, G and Beech, C and Roda, L}, title = {Means and ends of effective global risk assessments for genetic pest management.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 8}, pages = {13}, pmid = {30079104}, issn = {1753-6561}, abstract = {The development and use of genetic technologies is regulated by countries according to their national laws and governance structures. Legal frameworks require comprehensive technical evidence to be submitted by an applicant on the biology of the organism, its safety to human, animal health and the environment in which it will be released. Some countries also require information on socio-economic and trade impacts. One of the key elements that assists decision-making under those legal frameworks is the use of risk assessments. The risk assessment paradigm of problem formulation based on risk hypothesis, and the assessment of plausible scientific pathways leading to potential environmental and human harms being realised, has been used widely to assess potential risks of genetic technologies to human health and the environment, from crops to mosquitoes. This paper uses the case study of a genetically modified self-limiting olive fly (Bactrocera oleae) for a first deliberate release in Spain to examine the regulatory processes and stakeholders involved in the assessment of risk. It is anticipated that existing risk assessment frameworks are equally applicable to gene drive technologies that may spread and persist in the environment and cross-national borders, but it is the governance structures surrounding the involvement of civil society in regulatory processes that must be administered in a more transparent and defined manner.}, } @article {pmid30079103, year = {2018}, author = {Burgess, MM and Mumford, JD and Lavery, JV}, title = {Public engagement pathways for emerging GM insect technologies.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 8}, pages = {12}, pmid = {30079103}, issn = {1753-6561}, abstract = {Policy and management related to the release of organisms generated by emerging biotechnologies for pest management should be informed through public engagement. Regulatory decisions can be conceptually distinguished into the development of frameworks, the assessment of the release of a specific modified organism, and implementation decisions such as location and timing. Although these decisions are often intertwined in practice, the negotiation takes place at different stages of technology development and suggests different roles for public engagement. Some approaches to public engagement are more appropriate for different purposes and situations, and it is not always obvious how to go about matching the approach to the purpose. In addition to the diverse technologies involved in generating modified organisms, there are diverse publics with particular interests and different kinds of knowledge. Institutional interests range from commercial development to public regulation and future uptake. Contextual features, such as agency mandates, may limit or structure the extent and approach to public engagement. Different convening groups (government agencies, public interest groups, academics, businesses) and the kind of decision that is being considered determine what kind of input is needed and how the engaging groups will be constituted. This paper considers how the context of the release of genetically modified insects for pest control requires expanding approaches to the design of the public engagement.}, } @article {pmid30079102, year = {2018}, author = {Glover, B and Akinbo, O and Savadogo, M and Timpo, S and Lemgo, G and Sinebo, W and Akile, S and Obukosia, S and Ouedraogo, J and Ndomondo-Sigonda, M and Koch, M and Makinde, D and Ambali, A}, title = {Strengthening regulatory capacity for gene drives in Africa: leveraging NEPAD's experience in establishing regulatory systems for medicines and GM crops in Africa.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 8}, pages = {11}, pmid = {30079102}, issn = {1753-6561}, abstract = {The New Partnership for Africa's Development (NEPAD) Agency recognizes that Africa is in a period of transition and that this demands exploring and harnessing safe advances made in science-based innovations including modern biotechnology. To advance the science of biotechnology in Africa effectively, while at the same time safeguarding human health and the environment, the African Union (AU) adopted a High-Level Panel report on modern biotechnology entitled, Freedom to Innovate, which advocated for a coevolutionary approach where technology development goes hand in hand with regulation. Furthermore, most AU member states are Parties to the Cartagena Protocol on Biosafety (CPB), a legally binding international agreement negotiated, concluded and adopted within the framework of the Convention on Biological Diversity. This seeks to guide Parties in developing systems for the environmentally sound management of modern biotechnology applications. Currently, 49 AU Member States have signed and ratified the CPB, of which 12 have passed biosafety laws. African Union (AU) member states are at different stages in the development of regulatory frameworks for applications of modern biotechnology, which include genetically modified (GM) products and other emerging technologies. Biosafety regulatory frameworks comprise: biotechnology and/or biosafety policy; laws, regulations and guidelines; administrative systems; decision-making systems; and mechanisms for public engagement. To assist Member States to implement functional regulatory frameworks for both agriculture and health applications, the NEPAD Agency established the African Biosafety Network of Expertise (ABNE) and the African Medicines Regulatory Harmonization (AMRH). Currently, transgenic insects and GM crops are regulated by Competent National Authorities whose mandate derives from national biosafety laws. For GM crops, a lot of research has been conducted up to the confined field trial (CFT) and multi-location trials stages in a number of African countries. Burkina Faso has fully functional containment facilities for transgenic mosquitoes while Mali and Uganda are developing theirs. The Burkina Faso regulatory agency has granted permits and has already received sets of sterile mosquito eggs for trials in the contained facility. It is instructive to note that both ABNE and AMRH have worked with national and regional regulatory bodies in Africa to enhance their technical capacities for informed decision making, adoption of best practices, and compliance with international standards. It is against the backdrop of a rich blend of on-the-ground knowledge, experience, expertise, and insight into the context and political sensitivities of member states that the NEPAD Agency seeks to expand existing support. This would include capacity strengthening in the regulation of emerging technologies, such as the application of gene drives in the development of transgenic mosquito for the control of malaria transmission.}, } @article {pmid30079101, year = {2018}, author = {Collins, JP}, title = {Gene drives in our future: challenges of and opportunities for using a self-sustaining technology in pest and vector management.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 8}, pages = {9}, pmid = {30079101}, issn = {1753-6561}, abstract = {Gene drives are systems of biased inheritance that enhance the likelihood a sequence of DNA passes between generations through sexual reproduction and potentially throughout a local population and ultimately all connected populations of a species. Gaps in our knowledge of gene drive systems prompted the US National Institutes of Health (NIH) and the Foundation for the NIH to ask the US National Academies of Sciences, Engineering, and Medicine (NASEM) to convene an expert panel to provide an independent, objective examination of what we know about gene drive systems. The report, "Gene drives on the horizon: Advancing science, navigating uncertainty, and aligning research with public values," outlines our understanding of the science, ethics, public engagement, governance, and risk assessment pertaining to gene drive research. Researchers have studied naturally occurring gene drive systems for more than a century. While CRISPR/Cas9 was not the first molecular tool considered to create an engineered gene drive, the advent of the CRISPR/Cas9 technology for gene editing gave a renewed impetus to developing gene drives in the laboratory for eventual release in the field. Recent experiments demonstrate that a CRISPR/Cas9-based gene drive can spread a targeted gene throughout nearly all of laboratory populations of yeast, fruit flies, or mosquitoes. Applying this basic science, there are proposals to use gene drive modified organisms to address such things as eradication of insect-borne infectious diseases and conservation of threatened and endangered species. Gene drives could potentially support agriculture by reversing pesticide and herbicide resistance in insects and weeds, and by control of damaging, invasive species. A major recommendation of the NASEM report is that there is insufficient evidence at this time to support release of gene-drive modified organisms into the environment. Importantly, the committee also recognized that the potential benefits of gene drives for basic and applied research are significant and justify proceeding with laboratory research and controlled field trials. This review summarizes highlights of the NASEM report with its focus on using the CRISPR/Cas9 genome-editing technology to develop gene drive modified organisms.}, } @article {pmid30078701, year = {2018}, author = {White, MW and Suvorova, ES}, title = {Apicomplexa Cell Cycles: Something Old, Borrowed, Lost, and New.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {759-771}, pmid = {30078701}, issn = {1471-5007}, support = {R01 AI109843/AI/NIAID NIH HHS/United States ; R01 AI122760/AI/NIAID NIH HHS/United States ; }, abstract = {Increased parasite burden is linked to the severity of clinical disease caused by Apicomplexa parasites such as Toxoplasma gondii, Plasmodium spp, and Cryptosporidium. Pathogenesis of apicomplexan infections is greatly affected by the growth rate of the parasite asexual stages. This review discusses recent advances in deciphering the mitotic structures and cell cycle regulatory factors required by Apicomplexa parasites to replicate. As the molecular details become clearer, it is evident that the highly unconventional cell cycles of these parasites is a blending of many ancient and borrowed elements, which were then adapted to enable apicomplexan proliferation in a wide variety of different animal hosts.}, } @article {pmid30078068, year = {2018}, author = {Song, J and Wang, J and Sun, T and Li, C and He, H and Shi, L and Guo, X and Zhao, J and Xiang, W}, title = {Spirillospora tritici sp. nov., a Novel Actinomycete Isolated from Rhizosphere Soil of Triticum aestivum L.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1477-1483}, pmid = {30078068}, issn = {1432-0991}, support = {31672092//National Natural Science Foundation of China/ ; 31701858//National Natural Science Foundation of China/ ; }, mesh = {Actinobacteria/classification/enzymology/genetics/*isolation & purification ; Bacterial Proteins/genetics ; China ; DNA, Bacterial/genetics ; Nucleic Acid Hybridization ; Peptide Synthases/genetics ; Phylogeny ; Rhizosphere ; *Soil Microbiology ; Triticum/*growth & development/microbiology ; }, abstract = {A Gram-positive, aerobic actinomycetes, designated strain SJ 21T, was isolated from the rhizosphere soil of Triticum aestivum L. collected from Langfang, Hebei Province, Central China. Strain SJ 21T with weak antifungal activity also contained genes (involved in antibiotics biosynthesis) of the nonribosomal peptide synthetases (NRPS), ketosynthase (KS) and methyl malonyl transferase domains (PKS-I) as well as KSα and KSβ domains (PKS-II). A polyphasic taxonomic study was carried out to establish the status of strain SJ 21T. The strain formed spherical spore vesicles (7.0-8.9 µm) consisting of coiled and branched chains on aerial mycelia. 16S rRNA gene sequence similarity studies showed that strain SJ 21T belongs to the genus Spirillospora and formed a distinct branch with its closest neighbour Spirillospora albida IFO 12248T (98.7%). The morphological and chemotaxonomic properties of the strain are also consistent with those members of the genus Spirillospora. DNA-DNA hybridization experiments and phenotypic tests were carried out between strain SJ 21T and S. albida, which further clarified their relatedness and demonstrated that SJ 21T could be distinguished genomically from S. albida. Therefore, the strain is considered to represent a novel species of the genus Spirillospora, for which the name Spirillospora tritici sp. nov. is proposed. The type strain is SJ 21T (=CGMCC 4.7420T =JCM 32390T).}, } @article {pmid30078067, year = {2018}, author = {Javed, MR and Sadaf, M and Ahmed, T and Jamil, A and Nawaz, M and Abbas, H and Ijaz, A}, title = {CRISPR-Cas System: History and Prospects as a Genome Editing Tool in Microorganisms.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1675-1683}, pmid = {30078067}, issn = {1432-0991}, support = {NRPU Project # 5590//Higher Education Commission of Pakistan/ ; }, mesh = {Animals ; Bacteria/*genetics ; CRISPR-Cas Systems/*genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Gene Editing/methods ; Genetic Engineering/methods ; Genome/*genetics ; Humans ; }, abstract = {Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR or more precisely CRISPR-Cas) system has proven to be a highly efficient and simple tool for achieving site-specific genome modifications in comparison to Zinc Finger Nucleases (ZFNs) and Transcription Activator-Like Effector Nucleases (TALENs). The discovery of bacterial defense system that uses RNA-guided DNA cleaving enzymes for producing double-strand breaks along CRISPR has provided an exciting alternative to ZFNs and TALENs for gene editing & regulation, as the CRISPR-associated (Cas) proteins remain the same for different gene targets and only the short sequence of the guide RNA needs to be changed to redirect the site-specific cleavage. Therefore, in recent years the CRISPR-Cas system has emerged as a revolutionary engineering tool for carrying out precise and controlled genetic modifications in many microbes such as Escherichia coli, Staphylococcus aureus, Lactobacillus reuteri, Clostridium beijerinckii, Streptococcus pneumonia, and Saccharomyces cerevisiae. Though, concerns about CRISPR-Cas effectiveness in interlinked gene modifications and off-target effects need to be addressed. Nevertheless, it holds a great potential to speed up the pace of gene function discovery by interacting with previously intractable organisms and by raising the extent of genetic screens. Therefore, the potential applications of this system in microbial adaptive immune system, genome editing, gene regulations, functional genomics & biosynthesis along ethical issues, and possible harmful effects have been reviewed.}, } @article {pmid30077624, year = {2018}, author = {Wong, HC and Wang, TY and Yang, CW and Tang, CT and Ying, C and Wang, CH and Chang, WH}, title = {Characterization of a lytic vibriophage VP06 of Vibrio parahaemolyticus.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.07.003}, pmid = {30077624}, issn = {1769-7123}, abstract = {Vibrio parahaemolyticus is a human enteropathogenic bacterium and is also pathogenic to shrimp and finfish. In a search for a biocontrol agent for V. parahaemolyticus and other pathogenic Vibrio species, a lytic phage VP06 was isolated from oyster using V. parahaemolyticus as the host. VP06 is a Siphoviridae phage with a polyhedral head and a long tail. The genome sequence of VP06 was 75,893 nucleotides in length and the G + C content was 49%; a total of 101 CDSs were identified in VP06, of which 39 exhibited functional domains/motifs. The genomic sequence of VP06 is similar to those of a lytic Vibriovulnificus phage SSP002 and a temperate V. parahaemolyticus phage vB_VpaS_MAR10, although VP06 has distinct features in the CDS arrangement and 14 unique CDSs. Phylogenetic analysis revealed that VP06, SSP002 and vB_VpaS_MAR10 belong to a novel genus cluster of Siphoviridae phages. This phage lysed 28.1% of various Vibrio strains, and the efficiency of plating method revealed that VP06 was highly effective in lysing strains of Vibrioalginolyticus, Vibrioazureus, Vibrioharveyi and V. parahaemolyticus. The properties of VP06, including its broad range of hosts and resistance to environmental stresses, indicate that it may be a candidate biocontrol agent.}, } @article {pmid30077434, year = {2018}, author = {Larson, EL and Kopania, EEK and Good, JM}, title = {Spermatogenesis and the Evolution of Mammalian Sex Chromosomes.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {9}, pages = {722-732}, pmid = {30077434}, issn = {0168-9525}, support = {R01 GM098536/GM/NIGMS NIH HHS/United States ; R01 HD073439/HD/NICHD NIH HHS/United States ; R01 HD094787/HD/NICHD NIH HHS/United States ; }, abstract = {Developmental constraint and sexual conflict shape the evolution of heteromorphic sex chromosomes. These contrasting forces are perhaps strongest during spermatogenesis in species with XY males. In this review, we consider how the unique regulatory environment and selective pressures of spermatogenesis interact to impact sex chromosome evolution in mammals. We explore how each developmental phase of spermatogenesis influences sex chromosome gene content, structure, and rate of molecular evolution, and how these attributes may contribute to speciation. We argue that a developmental context is fundamental to understanding sex chromosome evolution and that an evolutionary perspective can shed new light on our understanding of sperm development.}, } @article {pmid30077182, year = {2018}, author = {Ye, Z and Zhang, N and Wu, C and Zhang, X and Wang, Q and Huang, X and Du, L and Cao, Q and Tang, J and Zhou, C and Hou, S and He, Y and Xu, Q and Xiong, X and Kijlstra, A and Qin, N and Yang, P}, title = {A metagenomic study of the gut microbiome in Behcet's disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {135}, pmid = {30077182}, issn = {2049-2618}, mesh = {Animals ; Bacteria/*classification/genetics/isolation & purification ; Bacterial Capsules/genetics ; Behcet Syndrome/*microbiology ; Case-Control Studies ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Gene Expression Regulation, Bacterial ; Humans ; Male ; Metagenomics/*methods ; Mice ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Saliva/microbiology ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Behcet's disease (BD) is a recalcitrant, multisystemic inflammatory disease that can lead to irreversible blindness. Microbial agents have been considered to contribute to the pathogenesis of this disease, but the underlying mechanisms remain unclear. In this study, we investigated the association of gut microbiome composition with BD as well as its possible roles in the development of this disease.

METHODS: Fecal and saliva samples were collected from 32 active BD patients and 74 healthy controls. DNA extracted from fecal samples was subjected to metagenomic analysis, whereas DNA extracted from saliva samples was subjected to 16S rRNA gene sequencing analysis. The results were used to compare the composition and biological function of the microbiome between patients and healthy controls. Lastly, transplantation of pooled fecal samples from active BD patients into B10RIII mice undergoing experimental autoimmune uveitis (EAU) was performed to determine the causal relationship between the gut microbiome and BD.

RESULTS: Fecal samples from active BD patients were shown to be enriched in Bilophila spp., a sulfate-reducing bacteria (SRB) and several opportunistic pathogens (e.g., Parabacteroides spp. and Paraprevotella spp.) along with a lower level of butyrate-producing bacteria (BPB) Clostridium spp. and methanogens (Methanoculleus spp. Methanomethylophilus spp.). Analysis of microbial functions revealed that capsular polysaccharide transport system, oxidation-reduction process, type III, and type IV secretion systems were also increased in active BD patients. Network analysis showed that the BD-enriched SRB and opportunistic pathogens were positively correlated with each other, but they were negatively associated with the BPB and methanogens. Animal experiments revealed that fecal microbiota transplantation with feces from BD patients significantly exacerbated EAU activity and increased the production of inflammatory cytokines including IL-17 and IFN-γ.

CONCLUSIONS: Our findings revealed that BD is associated with considerable gut microbiome changes, which is corroborated by a mouse study of fecal microbiota transplants. A model explaining the association of the gut microbiome composition with BD pathogenesis is proposed.}, } @article {pmid30076981, year = {2018}, author = {Sun, Y and Moore, MJ and Landis, JB and Lin, N and Chen, L and Deng, T and Zhang, J and Meng, A and Zhang, S and Tojibaev, KS and Sun, H and Wang, H}, title = {Plastome phylogenomics of the early-diverging eudicot family Berberidaceae.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {203-211}, doi = {10.1016/j.ympev.2018.07.021}, pmid = {30076981}, issn = {1095-9513}, abstract = {The relationships among the genera of the early-diverging eudicot family Berberidaceae have long been controversial. To resolve these relationships and to better understand plastome evolution within the family, we sequenced the complete plastome sequences of ten Berberidaceae genera, combined these with six existing plastomes for the family, and conducted a series of phylogenomic analyses on the resulting data set. Five of the newly sequenced plastomes were found to possess the typical angiosperm plastome complement of 79 protein-coding genes, 4 rRNA genes, and 30 tRNA genes. The infA gene was found to be pseudogenized in Bongardia, Diphylleia, Dysosma and Vancouveria; rps7 was found to be severely truncated in Diphylleia, Dysosma and Podophyllum; clpP was found to be highly divergent in Vancouveria; and a ∼19 kb inversion was detected in Bongardia. Maximum likelihood phylogenetic analyses of a 79-gene, 24-taxon data set including nearly all genera of Berberidaceae recovered four chromosome groups (x = 6, 7, 8, 10), resolved the x = 8 group as the sister to the x = 10 group, and supported the monophyly of the clade comprising x = 7, 8, 10. The generic relationships within each group were all resolved with high support. Based on gene presence within the Inverted Repeat (IR), a total of seven plastome IR types were identified within Berberidaceae. Biogeographical analysis indicated the origin and diversification of Berberidaceae has likely been strongly influenced by the distribution of its favored habitat: temperate forests.}, } @article {pmid30076406, year = {2018}, author = {Du Toit, A}, title = {Taking control over the host.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {582}, doi = {10.1038/s41579-018-0074-4}, pmid = {30076406}, issn = {1740-1534}, } @article {pmid30076405, year = {2018}, author = {Du Toit, A}, title = {Layers of complexity in the ground.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {582}, doi = {10.1038/s41579-018-0072-6}, pmid = {30076405}, issn = {1740-1534}, } @article {pmid30076404, year = {2018}, author = {Du Toit, A}, title = {Defending the niche.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {582}, doi = {10.1038/s41579-018-0073-5}, pmid = {30076404}, issn = {1740-1534}, } @article {pmid30076377, year = {2018}, author = {Birol, T}, title = {Stable and switchable electric polarization in two dimensions.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {174-175}, doi = {10.1038/d41586-018-05807-5}, pmid = {30076377}, issn = {1476-4687}, } @article {pmid30076376, year = {2018}, author = {Murphy, MP}, title = {Newly made mitochondrial DNA drives inflammation.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {176-177}, doi = {10.1038/d41586-018-05764-z}, pmid = {30076376}, issn = {1476-4687}, mesh = {*DNA, Mitochondrial ; Humans ; *Inflammasomes ; Inflammation ; Mitochondria/genetics ; NLR Family, Pyrin Domain-Containing 3 Protein ; }, } @article {pmid30076375, year = {2018}, author = {Catta-Preta, CMC and Mottram, JC}, title = {Drug candidate and target for leishmaniasis.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {171-172}, doi = {10.1038/d41586-018-05765-y}, pmid = {30076375}, issn = {1476-4687}, mesh = {Cyclins ; Drug Delivery Systems ; Humans ; *Leishmaniasis ; *Leishmaniasis, Visceral ; }, } @article {pmid30076374, year = {2018}, author = {Sweeney, MD and Zlokovic, BV}, title = {A lymphatic waste-disposal system implicated in Alzheimer's disease.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {172-174}, pmid = {30076374}, issn = {1476-4687}, support = {R01 AG023084/AG/NIA NIH HHS/United States ; R01 AG039452/AG/NIA NIH HHS/United States ; R01 NS034467/NS/NINDS NIH HHS/United States ; R01 NS100459/NS/NINDS NIH HHS/United States ; P01 AG052350/AG/NIA NIH HHS/United States ; }, } @article {pmid30076351, year = {2018}, author = {Nallu, S and Hill, JA and Don, K and Sahagun, C and Zhang, W and Meslin, C and Snell-Rood, E and Clark, NL and Morehouse, NI and Bergelson, J and Wheat, CW and Kronforst, MR}, title = {The molecular genetic basis of herbivory between butterflies and their host plants.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1418-1427}, pmid = {30076351}, issn = {2397-334X}, support = {R01 GM108626/GM/NIGMS NIH HHS/United States ; }, abstract = {Interactions between herbivorous insects and their host plants are a central component of terrestrial food webs and a critical topic in agriculture, where a substantial fraction of potential crop yield is lost annually to pests. Important insights into plant-insect interactions have come from research on specific plant defences and insect detoxification mechanisms. Yet, much remains unknown about the molecular mechanisms that mediate plant-insect interactions. Here we use multiple genome-wide approaches to map the molecular basis of herbivory from both plant and insect perspectives, focusing on butterflies and their larval host plants. Parallel genome-wide association studies in the cabbage white butterfly, Pieris rapae, and its host plant, Arabidopsis thaliana, pinpointed a small number of butterfly and plant genes that influenced herbivory. These genes, along with much of the genome, were regulated in a dynamic way over the time course of the feeding interaction. Comparative analyses, including diverse butterfly/plant systems, showed a variety of genome-wide responses to herbivory, as well as a core set of highly conserved genes in butterflies as well as their host plants. These results greatly expand our understanding of the genomic causes and evolutionary consequences of ecological interactions across two of nature's most diverse taxa, butterflies and flowering plants.}, } @article {pmid30076236, year = {2018}, author = {Dean, KR and Krauer, F and Walløe, L and Lingjærde, OC and Bramanti, B and Stenseth, NC and Schmid, BV}, title = {Reply to Park et al.: Human ectoparasite transmission of plague during the Second Pandemic is still plausible.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7894-E7895}, pmid = {30076236}, issn = {1091-6490}, mesh = {Disease Outbreaks ; Humans ; *Pandemics ; Plague/*epidemiology ; Yersinia pestis ; }, } @article {pmid30076235, year = {2018}, author = {Park, SW and Dushoff, J and Earn, DJD and Poinar, H and Bolker, BM}, title = {Human ectoparasite transmission of the plague during the Second Pandemic is only weakly supported by proposed mathematical models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7892-E7893}, pmid = {30076235}, issn = {1091-6490}, mesh = {Disease Outbreaks ; Humans ; Models, Theoretical ; *Pandemics ; Plague/*epidemiology ; Yersinia pestis ; }, } @article {pmid30076234, year = {2018}, author = {Matz, SC and Kosinski, M and Nave, G and Stillwell, DJ}, title = {Reply to Sharp et al.: Psychological targeting produces robust effects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7891}, pmid = {30076234}, issn = {1091-6490}, } @article {pmid30076233, year = {2018}, author = {Sharp, B and Danenberg, N and Bellman, S}, title = {Psychological targeting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7890}, pmid = {30076233}, issn = {1091-6490}, mesh = {*Stress, Psychological ; }, } @article {pmid30076232, year = {2018}, author = {Vikesland, PJ and Wei, H and Huang, Q and Guo, H and Marr, LC}, title = {Reply to Colussi: Microdroplet interfacial pH, the ongoing discussion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7888-E7889}, pmid = {30076232}, issn = {1091-6490}, mesh = {*Hydrogen-Ion Concentration ; *Software ; Surface Properties ; }, } @article {pmid30076231, year = {2018}, author = {Colussi, AJ}, title = {Can the pH at the air/water interface be different from the pH of bulk water?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7887}, pmid = {30076231}, issn = {1091-6490}, mesh = {*Air ; Hydrogen-Ion Concentration ; Surface Properties ; *Water ; }, } @article {pmid30076230, year = {2018}, author = {Richards, KL and Milligan, CJ and Richardson, RJ and Jancovski, N and Grunnet, M and Jacobson, LH and Undheim, EAB and Mobli, M and Chow, CY and Herzig, V and Csoti, A and Panyi, G and Reid, CA and King, GF and Petrou, S}, title = {Selective NaV1.1 activation rescues Dravet syndrome mice from seizures and premature death.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8077-E8085}, pmid = {30076230}, issn = {1091-6490}, mesh = {Animals ; CHO Cells ; Cricetulus ; Epilepsies, Myoclonic/*drug therapy/genetics/metabolism/pathology ; HEK293 Cells ; Humans ; Interneurons/*metabolism/pathology ; Mice ; Mice, Mutant Strains ; *Mutation ; NAV1.1 Voltage-Gated Sodium Channel/genetics/*metabolism ; Spider Venoms/*pharmacology ; Synaptic Transmission/*drug effects ; }, abstract = {Dravet syndrome is a catastrophic, pharmacoresistant epileptic encephalopathy. Disease onset occurs in the first year of life, followed by developmental delay with cognitive and behavioral dysfunction and substantially elevated risk of premature death. The majority of affected individuals harbor a loss-of-function mutation in one allele of SCN1A, which encodes the voltage-gated sodium channel NaV1.1. Brain NaV1.1 is primarily localized to fast-spiking inhibitory interneurons; thus the mechanism of epileptogenesis in Dravet syndrome is hypothesized to be reduced inhibitory neurotransmission leading to brain hyperexcitability. We show that selective activation of NaV1.1 by venom peptide Hm1a restores the function of inhibitory interneurons from Dravet syndrome mice without affecting the firing of excitatory neurons. Intracerebroventricular infusion of Hm1a rescues Dravet syndrome mice from seizures and premature death. This precision medicine approach, which specifically targets the molecular deficit in Dravet syndrome, presents an opportunity for treatment of this intractable epilepsy.}, } @article {pmid30076229, year = {2018}, author = {Kenseth, CM and Huang, Y and Zhao, R and Dalleska, NF and Hethcox, JC and Stoltz, BM and Seinfeld, JH}, title = {Synergistic O3 + OH oxidation pathway to extremely low-volatility dimers revealed in β-pinene secondary organic aerosol.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8301-8306}, pmid = {30076229}, issn = {1091-6490}, abstract = {Dimeric compounds contribute significantly to the formation and growth of atmospheric secondary organic aerosol (SOA) derived from monoterpene oxidation. However, the mechanisms of dimer production, in particular the relevance of gas- vs. particle-phase chemistry, remain unclear. Here, through a combination of mass spectrometric, chromatographic, and synthetic techniques, we identify a suite of dimeric compounds (C15-19H24-32O5-11) formed from concerted O3 and OH oxidation of β-pinene (i.e., accretion of O3- and OH-derived products/intermediates). These dimers account for an appreciable fraction (5.9-25.4%) of the β-pinene SOA mass and are designated as extremely low-volatility organic compounds. Certain dimers, characterized as covalent dimer esters, are conclusively shown to form through heterogeneous chemistry, while evidence of dimer production via gas-phase reactions is also presented. The formation of dimers through synergistic O3 + OH oxidation represents a potentially significant, heretofore-unidentified source of low-volatility monoterpene SOA. This reactivity also suggests that the current treatment of SOA formation as a sum of products originating from the isolated oxidation of individual precursors fails to accurately reflect the complexity of oxidation pathways at play in the real atmosphere. Accounting for the role of synergistic oxidation in ambient SOA formation could help to resolve the discrepancy between the measured atmospheric burden of SOA and that predicted by regional air quality and global climate models.}, } @article {pmid30076228, year = {2018}, author = {Flynn, GE and Zagotta, WN}, title = {Insights into the molecular mechanism for hyperpolarization-dependent activation of HCN channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8086-E8095}, pmid = {30076228}, issn = {1091-6490}, support = {R01 EY010329/EY/NEI NIH HHS/United States ; R01 MH102378/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cyclic Nucleotide-Gated Cation Channels/*chemistry/genetics/metabolism ; *Ion Channel Gating ; Protein Domains ; Sea Urchins/*chemistry/genetics/metabolism ; Structure-Activity Relationship ; }, abstract = {Hyperpolarization-activated, cyclic nucleotide-gated (HCN) ion channels are both voltage- and ligand-activated membrane proteins that contribute to electrical excitability and pace-making activity in cardiac and neuronal cells. These channels are members of the voltage-gated Kv channel superfamily and cyclic nucleotide-binding domain subfamily of ion channels. HCN channels have a unique feature that distinguishes them from other voltage-gated channels: the HCN channel pore opens in response to hyperpolarizing voltages instead of depolarizing voltages. In the canonical model of electromechanical coupling, based on Kv channels, a change in membrane voltage activates the voltage-sensing domains (VSD) and the activation energy passes to the pore domain (PD) through a covalent linker that connects the VSD to the PD. In this investigation, the covalent linkage between the VSD and PD, the S4-S5 linker, and nearby regions of spHCN channels were mutated to determine the functional role each plays in hyperpolarization-dependent activation. The results show that: (i) the S4-S5 linker is not required for hyperpolarization-dependent activation or ligand-dependent gating; (ii) the S4 C-terminal region (S4C-term) is not necessary for ligand-dependent gating but is required for hyperpolarization-dependent activation and acts like an autoinhibitory domain on the PD; (iii) the S5N-term region is involved in VSD-PD coupling and holding the pore closed; and (iv) spHCN channels have two voltage-dependent processes, a hyperpolarization-dependent activation and a depolarization-dependent recovery from inactivation. These results are inconsistent with the canonical model of VSD-PD coupling in Kv channels and elucidate the mechanism for hyperpolarization-dependent activation of HCN channels.}, } @article {pmid30076227, year = {2018}, author = {Cheng, T and Jaramillo-Botero, A and An, Q and Ilyin, DV and Naserifar, S and Goddard, WA}, title = {First principles-based multiscale atomistic methods for input into first principles nonequilibrium transport across interfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1800035115}, pmid = {30076227}, issn = {1091-6490}, abstract = {This issue of PNAS features "nonequilibrium transport and mixing across interfaces," with several papers describing the nonequilibrium coupling of transport at interfaces, including mesoscopic and macroscopic dynamics in fluids, plasma, and other materials over scales from microscale to celestial. Most such descriptions describe the materials in terms of the density and equations of state rather than specific atomic structures and chemical processes. It is at interfacial boundaries where such atomistic information is most relevant. However, there is not yet a practical way to couple these phenomena with the atomistic description of chemistry. The starting point for including such information is the quantum mechanics (QM). However, practical QM calculations are limited to a hundred atoms for dozens of picoseconds, far from the scales required to inform the continuum level with the proper atomistic description. To bridge this enormous gap, we need to develop practical methods to extend the scale of the atomistic simulation by several orders of magnitude while retaining the level of QM accuracy in describing the chemical process. These developments would enable continuum modeling of turbulent transport at interfaces to incorporate the relevant chemistry. In this perspective, we will focus on recent progress in accomplishing these extensions in first principles-based atomistic simulations and the strategies being pursued to increase the accuracy of very large scales while dramatically decreasing the computational effort.}, } @article {pmid30076226, year = {2018}, author = {Gong, SJ and Gong, C and Sun, YY and Tong, WY and Duan, CG and Chu, JH and Zhang, X}, title = {Electrically induced 2D half-metallic antiferromagnets and spin field effect transistors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8511-8516}, pmid = {30076226}, issn = {1091-6490}, abstract = {Engineering the electronic band structure of material systems enables the unprecedented exploration of new physical properties that are absent in natural or as-synthetic materials. Half metallicity, an intriguing physical property arising from the metallic nature of electrons with singular spin polarization and insulating for oppositely polarized electrons, holds a great potential for a 100% spin-polarized current for high-efficiency spintronics. Conventionally synthesized thin films hardly sustain half metallicity inherited from their 3D counterparts. A fundamental challenge, in systems of reduced dimensions, is the almost inevitable spin-mixed edge or surface states in proximity to the Fermi level. Here, we predict electric field-induced half metallicity in bilayer A-type antiferromagnetic van der Waals crystals (i.e., intralayer ferromagnetism and interlayer antiferromagnetism), by employing density functional theory calculations on vanadium diselenide. Electric fields lift energy levels of the constituent layers in opposite directions, leading to the gradual closure of the gap of singular spin-polarized states and the opening of the gap of the others. We show that a vertical electrical field is a generic and effective way to achieve half metallicity in A-type antiferromagnetic bilayers and realize the spin field effect transistor. The electric field-induced half metallicity represents an appealing route to realize 2D half metals and opens opportunities for nanoscale highly efficient antiferromagnetic spintronics for information processing and storage.}, } @article {pmid30076225, year = {2018}, author = {Xu, Y and Sommerdijk, NAJM}, title = {Aragonite formation in confinements: A step toward understanding polymorph control.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8469-8471}, pmid = {30076225}, issn = {1091-6490}, } @article {pmid30075901, year = {2018}, author = {Hébert, FO and Boyle, B and Levesque, RC}, title = {Direct In Vivo Microbial Transcriptomics During Infection.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {732-735}, doi = {10.1016/j.tim.2018.07.002}, pmid = {30075901}, issn = {1878-4380}, abstract = {The challenge in infectious diseases is monitoring infection in the host. Omics-based genomics and transcriptomics can define microbial genes expressed during infection and treatment with antimicrobials. Recent studies pinpoint a direct in situ in vivo approach revolutionizing infection monitoring and optimizing antimicrobial therapy using machine learning.}, } @article {pmid30075872, year = {2018}, author = {Boyle, EK and McNutt, EJ and Sasaki, T and Suwa, G and Zipfel, B and DeSilva, JM}, title = {A quantification of calcaneal lateral plantar process position with implications for bipedal locomotion in Australopithecus.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {24-34}, doi = {10.1016/j.jhevol.2018.05.008}, pmid = {30075872}, issn = {1095-8606}, abstract = {The evolution of bipedalism in the hominin lineage has shaped the posterior human calcaneus into a large, robust structure considered to be adaptive for dissipating peak compressive forces and energy during heel-strike. A unique anatomy thought to contribute to the human calcaneus and its function is the lateral plantar process (LPP). While it has long been known that humans possess a plantarly positioned LPP and apes possess a more dorsally positioned homologous structure, the relative position of the LPP and intraspecific variation of this structure have never been quantified. Here, we present a method for quantifying relative LPP position and find that, while variable, humans have a significantly more plantar position of the LPP than that found in the apes. Among extinct hominins, while the position of the LPP in Australopithecus afarensis falls within the human distribution, the LPP is more dorsally positioned in Australopithecus sediba and barely within the modern human range of variation. Results from a resampling procedure suggest that these differences can reflect either individual variation of a foot structure/function largely shared among Australopithecus species, or functionally distinct morphologies that reflect locomotor diversity in Plio-Pleistocene hominins. An implication of the latter possibility is that calcaneal changes adaptive for heel-striking bipedalism may have evolved independently in two different hominin lineages.}, } @article {pmid30075824, year = {2018}, author = {Abera, L and Dejene, T and Laelago, T}, title = {Magnitude of stunting and its determinants in children aged 6-59 months among rural residents of Damot Gale district; southern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {557}, pmid = {30075824}, issn = {1756-0500}, mesh = {Child ; Child, Preschool ; Cross-Sectional Studies ; Ethiopia ; Female ; *Growth Disorders ; Humans ; Infant ; Male ; Risk Factors ; *Rural Population ; }, abstract = {OBJECTIVE: The objective of this study is assessing magnitude of stunting and its predictors among children aged 6-59 months in Damot Gale district, South Ethiopia. Community based cross sectional study was done at Damot Gale district. About 398 children aged 6-59 months were included in the study. Kebele (small administrative unit) and household were chosen by two-phase cluster sample design. Structured questionnaire was used to gather the data. Anthropometric measurement was also used to get the data. SPSS version 20 was used to analysis the data.

RESULTS: About 41.7% of children were stunted. Children aged 36-47 months [AOR 6.22; 95% CI (1.81-21.36)], and 48-59 months [AOR 7.27; 95% CI (1.22-43.19)], sex of the child [AOR 20.79; 95% CI (7.50-57.65)], birth order [AOR 6.42; 95% CI (1.68-24.48)], mother education [AOR 0.06; 95% CI (0.02-0.14)], having toilet facility [AOR 0.059; 95% CI (0.02-0.18)], washing hand by soap [AOR 16.21; 95% CI (5.11-51.4)] and ANC [AOR 0.045; 95% CI (0.01-0.13)] were associated with stunting.}, } @article {pmid30075823, year = {2018}, author = {Holmes, DR and Grubb, LE and Monaghan, J}, title = {The jasmonate receptor COI1 is required for AtPep1-induced immune responses in Arabidopsis thaliana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {555}, pmid = {30075823}, issn = {1756-0500}, support = {RGPIN-2016-04787//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Arabidopsis/*physiology ; Arabidopsis Proteins/*physiology ; Cyclopentanes/metabolism ; Gene Expression Regulation, Plant ; Mutation ; Oxylipins/metabolism ; Plant Growth Regulators ; Signal Transduction ; Trans-Activators/*physiology ; }, abstract = {OBJECTIVE: Plant cells detect the presence of potentially pathogenic microorganisms in the apoplast via plasma membrane-localized receptors. Activated receptors trigger phosphorylation-mediated signaling cascades that protect the cell from infection. It is thought that signaling triggered by the detection of exogenous signals, such as bacterial flagellin, can be amplified by endogenous signals, such as hormones or debris caused by cell damage, to potentiate robust immune responses. For example, perception of flagellin and other microbial molecules results in increased expression of endogenous PROPEP transcripts that give rise to AtPep peptides which also activate immune signaling. Phytohormones such as methyl-jasmonate also induce PROPEP expression, suggestive of additional hormone-mediated feedback loops that similarly amplify immune signaling. The current study aimed to determine if perception of jasmonate is genetically required for AtPep1-induced immune responses in Arabidopsis thaliana.

RESULTS: We assessed several AtPep1-induced immune responses in plants expressing a non-functional variant of the jasmonate receptor CORONATINE-INSENSITIVE 1 (COI1). We found that coi1-16 mutants are severely compromised in some AtPep1-induced immune responses, while other AtPep1-induced responses are maintained but reduced. Our findings build on previously published work and suggest that JA perception plays a role in immune responses triggered by AtPep1.}, } @article {pmid30075822, year = {2018}, author = {Sakisaka, K}, title = {Identification of high risk groups with shorter survival times after onset of the main reason for suicide: findings from interviews with the bereaved in Japan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {553}, pmid = {30075822}, issn = {1756-0500}, mesh = {Adult ; Family ; Female ; Humans ; Japan ; Male ; Middle Aged ; *Suicide, Attempted ; Surveys and Questionnaires ; Survival Analysis ; }, abstract = {OBJECTIVES: We sought to (1) measure survival lengths after the onset of the main reason for the target's suicide, (2) identify the highest-risk groups and the contributors to early death, in Japan, and (3) clarify peculiar traditional Japanese values concerning suicide.

RESULTS: Data for 523 deceased individuals (median age 43.0 years) were collected from bereaved persons. Average survival time from the onset of the main reason for suicide was 1956 days (5.4 years). After controlling for confounding factors, being middle-aged, male, self-employed, and a founding company president were identified as the highest-risk groups. Half of the self-employed founding presidents died within 2 years. Many of the bereaved had observed some signs of the suicide 2 weeks ago. The traditional Japanese idea is that one means of compensating for a serious mistake is to commit suicide, and we observed that many Japanese people still regard suicide as a respectable death, even among the interviewed. The possible intervention time is quite limited; however, those who have contact with the high-risk groups should be alert to behavioral changes or signals of impending suicide.}, } @article {pmid30075812, year = {2018}, author = {Matthias, AT and Fernandopulle, ANR and Seneviratne, SL}, title = {Survey on knowledge of non-alcoholic fatty liver disease (NAFLD) among doctors in Sri Lanka: a multicenter study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {556}, pmid = {30075812}, issn = {1756-0500}, mesh = {Diabetes Mellitus ; *Health Knowledge, Attitudes, Practice ; Humans ; *Non-alcoholic Fatty Liver Disease/diagnosis/therapy ; Physicians ; Pilot Projects ; Risk Factors ; Sri Lanka ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: There has been a global increase in the incidence and prevalence of NAFLD. We assessed the knowledge and awareness of NAFLD among gastroenterology doctors in three state sector hospitals.

RESULTS: 80 medical officers and 58 post-graduate trainee doctors/consultants responded. 110 (79.7%) considered NAFLD a major health problem whilst 97 (70.3%) thought the prevalence of NAFLD was 10-40%. 52.9% saw 12-24 patients with NAFLD/year. A vast majority knew the risk factors for NAFLD: 127 (92.7%) diabetes mellitus, 135 (97.8%) Obesity, 132 (95.7%) Dyslipidemia and 87 (63%) PCOS. The methods for diagnosis were recognized by: USS 132 (95.7%), MRI 34 (24.6%), transient elastography 23 (16.7%) and liver biopsy 88 (63.8%) while, 53 (38.4%) recognized the non-invasive methods available for diagnosis. The trends in referral were lower than expected: 85 (61.6%) refer to a Gastroenterologist/Physician, 53 (38.4%) to a Gym, 67 (48.6%) to a weight loss clinic and 45 (32.6%) to a dietician. Significantly more postgraduate trainee doctors: recognized the availability of non-invasive investigations for NAFLD (P = 0.01) and read guidelines on NAFLD (P = 0.02) compared to non-trainee doctors. As a whole, a majority (57.2%) had not attended a lecture or read a guideline on NAFLD. The barriers for management included: lack of confidence 70 (50.7%) and time constraints 58 (42%).}, } @article {pmid30075807, year = {2018}, author = {Hill, JN and Locatelli, SM and Bokhour, BG and Fix, GM and Solomon, J and Mueller, N and LaVela, SL}, title = {Evaluating broad-scale system change using the Consolidated Framework for Implementation Research: challenges and strategies to overcome them.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {560}, pmid = {30075807}, issn = {1756-0500}, support = {PCE 13-002//Department of Veterans Affairs/ ; PCE 13-001//Department of Veterans Affairs/ ; }, mesh = {*Delivery of Health Care ; Humans ; *Patient-Centered Care ; Qualitative Research ; }, abstract = {OBJECTIVE: The objective of this paper is to demonstrate the utility of the CFIR framework for evaluating broad-scale change by discussing the challenges to be addressed when planning the assessment of broad-scale change and the solutions developed by the evaluation team to address those challenges. The evaluation of implementation of Patient-centered Care and Cultural Transformation (PCC&CT) within the Department of Veterans Affairs (VA) will be used as a demonstrative example. Patient-Centered Care (PCC) is personalized health care that considers a patient's circumstances and goals. The Department of Veterans Affairs (VA) is working towards implementing PCC throughout its healthcare system, comprised of multiple interventions with a singular long-term goal of cultural transformation, however little is known about the factors influencing its implementation. This paper discusses the issues that arose using CFIR to qualitatively assess the factors influencing implementation of cultural transformation.

RESULTS: Application of CFIR to this broad-scale evaluation revealed three strategies recommended for use in evaluating implementation of broad-scale change: (1) the need for adapted definitions for CFIR constructs (especially due to new application to broad-scale change), (2) the use of a mixed deductive-inductive approach with thematic coding to capture emergent themes not encompassed by CFIR, and (3) its use for expedited analysis and synthesis for rapid delivery of findings to operational partners. This paper is among the first to describe use of CFIR to guide the evaluation of a broad-scale transformation, as opposed to discrete interventions. The processes and strategies described in this paper provide a detailed example and structured approach that can be utilized and expanded upon by others evaluating implementation of broad-scale evaluations. Although CFIR was the framework selected for this evaluation, the strategies described in this paper including: use of adapted definitions, use of mixed deductive-inductive approach, and the approach for expedited analysis and synthesis can be transferred and tested with other frameworks.}, } @article {pmid30075803, year = {2018}, author = {Tamiru, A and Edessa, D and Sisay, M and Mengistu, G}, title = {Magnitude and factors associated with medication discrepancies identified through medication reconciliation at care transitions of a tertiary hospital in eastern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {554}, pmid = {30075803}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Ethiopia ; Female ; Humans ; Male ; Medication Errors ; *Medication Reconciliation ; Middle Aged ; *Patient Transfer ; Pharmacists ; *Tertiary Care Centers ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study is to determine the magnitude of medication discrepancies and its associated factors at transitions in care of a Specialized University Hospital in eastern Ethiopia.

RESULTS: This study enrolled 411 patients having at least one prescription medication. For each of the patient enrolled, a medication reconciliation process was accomplished between medication use history before transition and medication orders at the transition. A total of 1027 medications were reconciled and 298 of them showed discrepancies. From such medication discrepancies, 96 (32.2%) of them were unintended discrepancies. Patients admitted to surgical ward (adjusted odds ratio {AOR} 0.27 [95% confidence interval 0.10-0.74]) and on malnutrition therapy (AOR 0.13 [0.03-0.52]) had reduced likelihoods of medication discrepancies. However, patients on cardiovascular drug therapy (AOR 5.69 [2.4-13.62]) and who were hospitalized for more than 5 days (AOR 5.69 [2.97-10.9] {5-10 days}) had significantly increased likelihoods of discrepancies. Accordingly, one-third of the medication discrepancies identified were unintentional and these discrepancies were more likely to occur with cardiovascular drugs, in medical or pediatric wards and patients hospitalized for prolonged time. Therefore, this pharmacist-led medication reconciliation indicates the potential of pharmacists in reducing drug-related adverse health outcomes that arise from medication discrepancy.}, } @article {pmid30075801, year = {2018}, author = {Agbor, NE and Esemu, SN and Ndip, LM and Tanih, NF and Smith, SI and Ndip, RN}, title = {Helicobacter pylori in patients with gastritis in West Cameroon: prevalence and risk factors for infection.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {559}, pmid = {30075801}, issn = {1756-0500}, mesh = {Cameroon ; Female ; Gastritis/complications/*microbiology ; Helicobacter Infections/complications/*epidemiology ; Helicobacter pylori/*isolation & purification ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; }, abstract = {OBJECTIVES: Helicobacter pylori is a pathogenic bacterium that parasitizes the gastric mucous layer and the epithelial lining of the stomach causing duodenal ulcers, gastric ulcers and cardiovascular disease amongst others. This study aimed at establishing the epidemiologic profile of H. pylori infection in gastritis patients presenting at the Melong District Hospital.

RESULTS: Blood, stool and epidemiological data collected from 500 patients were analyzed for the presence of H. pylori antibody in serum, antigen in stool and elucidation of risk factors captured in questionnaires. Of 500 blood samples, 217 (43.4%) were seropositive with male and female seroprevalences of 45.5% (61/134) and 42.6% (156/366) respectively. Similarly, 47.4% (237/500) samples tested positive for stool antigen with prevalences of 47.0% (63/134) for males and 47.5% (174/366) for females. The antigen prevalence was higher (53.2%; 118/222) in older patients (> 50 years) than in younger patients (42.8%; 119/278; P = 0.021). The antigen test had a higher (47.4%) prevalence than the antibody test (43.4%). Educational level, source of income, source of drinking water, age of patients, and alcohol consumption had positive associations with H. pylori infection. These results have clinical and epidemiological significance and call for intervention to mitigate the situation.}, } @article {pmid30075799, year = {2018}, author = {Scheinfeldt, LB and Hodges, K and Pevsner, J and Berlin, D and Turan, N and Gerry, NP}, title = {Genetic and genomic stability across lymphoblastoid cell line expansions.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {558}, pmid = {30075799}, issn = {1756-0500}, support = {U42 GM115336/GM/NIGMS NIH HHS/United States ; 5U42GM115336//National Institute of General Medical Sciences/ ; }, mesh = {B-Lymphocytes/*cytology ; Cell Line ; DNA ; Genetic Variation ; *Genomic Instability ; Humans ; Polymorphism, Single Nucleotide ; }, abstract = {OBJECTIVE: Lymphoblastoid cell lines are widely used in genetic and genomic studies. Previous work has characterized variant stability in transformed culture and across culture passages. Our objective was to extend this work to evaluate single nucleotide polymorphism and structural variation across cell line expansions, which are commonly used in biorepository distribution. Our study used DNA and cell lines sampled from six research participants. We assayed genome-wide genetic variants and inferred structural variants for DNA extracted from blood, from transformed cell cultures, and from three generations of expansions.

RESULTS: Single nucleotide variation was stable between DNA and expanded cell lines (ranging from 99.90 to 99.98% concordance). Structural variation was less consistent across expansions (median 33% concordance) with a noticeable decrease in later expansions. In summary, we demonstrate consistency between SNPs assayed from whole blood DNA and LCL DNA; however, more caution should be taken in using LCL DNA to study structural variation.}, } @article {pmid30075778, year = {2018}, author = {Hariharan, P and Tikhonova, E and Medeiros-Silva, J and Jeucken, A and Bogdanov, MV and Dowhan, W and Brouwers, JF and Weingarth, M and Guan, L}, title = {Structural and functional characterization of protein-lipid interactions of the Salmonella typhimurium melibiose transporter MelB.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {85}, pmid = {30075778}, issn = {1741-7007}, support = {R01 GM122759/GM/NIGMS NIH HHS/United States ; R21 NS105863/NS/NINDS NIH HHS/United States ; R21NS105863/NS/NINDS NIH HHS/United States ; RO1GM121493/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Membrane lipids play critical roles in the structure and function of membrane-embedded transporters. Salmonella typhimurium MelB (MelBSt) is a symporter coupling melibiose translocation with a cation (Na+, Li+, or H+). We present an extensive study on the effects of specific phospholipids on the structure of MelBSt and the melibiose transport catalyzed by this protein.

RESULTS: Lipidomic analysis and thin-layer chromatography (TLC) experiments reveal that at least one phosphatidylethanolamine (PE) and one phosphatidylglycerol (PG) molecule associate with MelBSt at high affinities. Solid-state nuclear magnetic resonance (ssNMR) spectroscopy experiments confirmed the presence of lipid tails and glycerol backbones that co-purified with MelBSt; headgroups of PG were also observed. Studies with lipid-engineered strains, including PE-deficient, cardiolipin (CL)- and PG-deficient, or CL-deficient strains, show that lack of PE or PG, however not CL, largely inhibits both H+- and Na+-coupled melibiose active transport to different extents. Interestingly, neither the co-substrate binding (melibiose or Na+) nor MelBSt folding and stability are affected by changing lipid compositions. Remarkably, the delipidated MelBSt with only 2-3 bound lipids, regardless of the headgroup species, also exhibits unchanged melting temperature values as shown by circular dichroism spectroscopy.

CONCLUSIONS: (1) Lipid tails and glycerol backbones of interacting PE and PG may contribute to the stability of the structure of MelBSt. (2) The headgroups of PE and PG, but not of CL, play important roles in melibiose transport; however, lipid headgroups do not modulate the folding and stability of MelBSt.}, } @article {pmid30075756, year = {2018}, author = {Burke, SV and Ungerer, MC and Duvall, MR}, title = {Investigation of mitochondrial-derived plastome sequences in the Paspalum lineage (Panicoideae; Poaceae).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {152}, pmid = {30075756}, issn = {1471-2229}, support = {DEB-1120856//National Science Foundation/ ; DEB-1120761//National Science Foundation/ ; }, abstract = {BACKGROUND: The grass family (Poaceae), ca. 12,075 species, is a focal point of many recent studies that aim to use complete plastomes to reveal and strengthen relationships within the family. The use of Next Generation Sequencing technology has revealed intricate details in many Poaceae plastomes; specifically the trnI - trnL intergenic spacer region. This study investigates this region and the putative mitochondrial inserts within it in complete plastomes of Paspalum and other Poaceae.

RESULTS: Nine newly sequenced plastomes, seven of which contain an insert within the trnI - trnL intergenic spacer, were combined into plastome phylogenomic and divergence date analyses with 52 other species. A robust Paspalum topology was recovered, originating at 10.6 Ma, with the insert arising at 8.7 Ma. The alignment of the insert across Paspalum reveals 21 subregions with pairwise homology in 19. In an analysis of emergent self-organizing maps of tetranucleotide frequencies, the Paspalum insert grouped with mitochondrial DNA.

CONCLUSIONS: A hypothetical ancestral insert, 17,685 bp in size, was found in the trnI - trnL intergenic spacer for the Paspalum lineage. A different insert, 2808 bp, was found in the same region for Paraneurachne muelleri. Seven different intrastrand deletion events were found within the Paspalum lineage, suggesting selective pressures to remove large portions of noncoding DNA. Finally, a tetranucleotide frequency analysis was used to determine that the origin of the insert in the Paspalum lineage is mitochondrial DNA.}, } @article {pmid30075753, year = {2018}, author = {Gogoi, B and Bhau, BS}, title = {DNA barcoding of the genus Nepenthes (Pitcher plant): a preliminary assessment towards its identification.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {153}, pmid = {30075753}, issn = {1471-2229}, abstract = {BACKGROUND: DNA barcoding is impending towards the generation of universal standards for species discrimination with a standard gene region that can be sequenced accurately and within short span of time. In this study, we were successful in developing efficient barcode locus in the Nepenthes genus. A total of 317 accessions were retrieved from GenBank of NCBI which represent 140 different species Nepenthes and evaluated the efficacy of ITS, rbcl and matK barcode candidates using barcode gap, applied distance similarity, and tree-based methods.

RESULT: Our result indicates that single-locus ITS or combined with plastid regions (matK) showed the best species discrimination with distinctive barcoding gaps. Therefore, we tentatively proposed the combination of ITS+matK as a core barcode for Nepenthes genus.

CONCLUSION: This study provides a report on DNA barcoding for unique insectivores' Nepenthes genus. As the different species of Nepenthes are higly endemic and endangered, it would be a useful study to understand the evolutionary relationship, sketched in emigration, mislabeling and can be a probable assessment for its biodiversity.}, } @article {pmid30075750, year = {2018}, author = {Wang, X and Cheng, C and Zhang, K and Tian, Z and Xu, J and Yang, S and Lou, Q and Li, J and Chen, JF}, title = {Comparative transcriptomics reveals suppressed expression of genes related to auxin and the cell cycle contributes to the resistance of cucumber against Meloidogyne incognita.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {583}, pmid = {30075750}, issn = {1471-2164}, support = {31430075//National Natural Science Foundation of China/ ; 31572134//National Natural Science Foundation of China/ ; 31471872//National Natural Science Foundation of China/ ; 31672168//National Natural Science Foundation of China/ ; 201403032//Special Fund for Agro-Scientific Research in the Public Interest/ ; 2016YFD0101705-5//National Key Research and Development Program of China/ ; 2016YFD0100204-25//National Key Research and Development Program of China/ ; CX (15) 1019//Agricultural science and Technology Innovation Fund of Jiangsu Province/ ; }, mesh = {Animals ; Cell Cycle ; Cucumis sativus/genetics/*growth & development/parasitology ; *Disease Resistance ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant ; Gene Ontology ; Gene Regulatory Networks ; Indoleacetic Acids/metabolism ; Plant Breeding ; Plant Diseases/genetics/*parasitology ; Plant Proteins/*genetics ; Tylenchoidea/physiology ; }, abstract = {BACKGROUND: Meloidogyne incognita is a devastating nematode that causes significant losses in cucumber production worldwide. Although numerous studies have emphasized on the susceptible response of plants after nematode infection, the exact regulation mechanism of M. incognita-resistance in cucumber remains elusive. Verification of an introgression line, 'IL10-1', with M. incognita-resistance provides the opportunity to unravel the resistance mechanism of cucumber against M. incognita.

RESULTS: In the present study, analyses of physiological responses and transcriptional events between IL10-1 (resistant line) and CC3 (susceptible line) were conducted after M. incognita infection. Physiological observations showed abnormal development of giant cells and M. incognita in IL10-1, which were the primary differences compared with CC3. Furthermore, Gene ontology (GO) analysis revealed that genes encoding cell wall proteins were up-regulated in IL10-1 and that the highly expressed lipid transfer protein gene (Csa6G410090) might be the principal regulator of this up-regulation. Simultaneously, analyses of gene expression profiles revealed more auxin-related genes were suppressed in IL10-1 than in those of CC3, which corresponded with the lower level of indole acetic acid (IAA) in the roots of IL10-1 than in those of CC3. Additionally, poor nucleus development as a clear indication of abnormal giant cells in IL10-1 was related to inhibition of the cell cycle. Of those genes related to the cell cycle, the F-box domain Skp2-like genes were down-regulated in IL10-1, whereas more of these genes were up-regulated in CC3.

CONCLUSIONS: All of these findings indicate that suppressed expression of genes related to auxin and the cell cycle and highly expressed cell wall proteins play important roles in the abnormal development of giant cells, which hinders the development of M. incognita, thereby causing resistance to M. incognita in IL10-1. Knowledge from this research will provide a useful foundation for developing effective strategies in M. incognita-resistance breeding.}, } @article {pmid30075747, year = {2018}, author = {Chen, J and Su, P and Chen, P and Li, Q and Yuan, X and Liu, Z}, title = {Insights into the cotton anther development through association analysis of transcriptomic and small RNA sequencing.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {154}, pmid = {30075747}, issn = {1471-2229}, support = {Nos. 31771847//National Natural Science Foundation of China/ ; U1403284//National Natural Science Foundation of China/ ; CX2017B360//Graduate student research innovation project of Hunan province/ ; }, abstract = {BACKGROUND: Plant anther development is a systematic and complex process precisely controlled by genes. Regulation genes and their regulatory mechanisms for this process remain elusive. In contrast to numerous researches on anther development with respect to mRNAs or miRNAs in many crops, the association analysis combining both omics has not been reported on cotton anther.

RESULTS: In this study, the molecular mechanism of cotton anther development was investigated with the employment of association analysis of transcriptome and small RNA sequencing during the predefined four stages of cotton anther development, sporogenuous cell proliferation (SCP), meiotic phase (MP), microspore release period (MRP) and pollen maturity (PM). Analysis revealed that the differentially expressed genes are increasingly recruited along with the developmental progress. Expression of functional genes differed significantly among developmental stages. The genes related with cell cycle, progesterone-mediated oocyte maturation, and meiosis are predominantly expressed at the early stage of anther development (SCP and MP), and the expression of genes involved in energy metabolism, flavonoid biosynthesis, axon guidance and phospholipase D signaling pathways is mainly enriched at the late stage of anther development (MRP and PM). Analysis of expression patterns revealed that there was the largest number of differentially expressed genes in the MP and the expression profiles of differentially expressed genes were significantly increased, which implied the importance of MP in the entire anther development cycle. In addition, prediction and analysis of miRNA targeted genes suggested that miRNAs play important roles in anther development. The miRNAs ghr-miR393, Dt_chr12_6065 and At_chr9_3080 participated in cell cycle, carbohydrate metabolism and auxin anabolism through the target genes, respectively, to achieve the regulation of anther development.

CONCLUSIONS: Through the association analysis of mRNA and miRNA, our work gives a better understanding of the preferentially expressed genes and regulation in different developmental stages of cotton anther and the importance of meiotic phase, and also the involvement of miRNAs in precise regulation for this process, which would be valuable for clarifying the mechanism of plant anther development in response to internal and external environments.}, } @article {pmid30075707, year = {2018}, author = {Zhang, B and Li, J and Lü, Q}, title = {Prediction of 8-state protein secondary structures by a novel deep learning architecture.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {293}, pmid = {30075707}, issn = {1471-2105}, abstract = {BACKGROUND: Protein secondary structure can be regarded as an information bridge that links the primary sequence and tertiary structure. Accurate 8-state secondary structure prediction can significantly give more precise and high resolution on structure-based properties analysis.

RESULTS: We present a novel deep learning architecture which exploits an integrative synergy of prediction by a convolutional neural network, residual network, and bidirectional recurrent neural network to improve the performance of protein secondary structure prediction. A local block comprised of convolutional filters and original input is designed for capturing local sequence features. The subsequent bidirectional recurrent neural network consisting of gated recurrent units can capture global context features. Furthermore, the residual network can improve the information flow between the hidden layers and the cascaded recurrent neural network. Our proposed deep network achieved 71.4% accuracy on the benchmark CB513 dataset for the 8-state prediction; and the ensemble learning by our model achieved 74% accuracy. Our model generalization capability is also evaluated on other three independent datasets CASP10, CASP11 and CASP12 for both 8- and 3-state prediction. These prediction performances are superior to the state-of-the-art methods.

CONCLUSION: Our experiment demonstrates that it is a valuable method for predicting protein secondary structure, and capturing local and global features concurrently is very useful in deep learning.}, } @article {pmid30075706, year = {2018}, author = {Hadwan, MH}, title = {Simple spectrophotometric assay for measuring catalase activity in biological tissues.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {7}, pmid = {30075706}, issn = {1471-2091}, mesh = {Artifacts ; Bacteria/enzymology ; Catalase/blood/*metabolism ; Cobalt/metabolism ; Enzyme Assays ; Erythrocytes/enzymology ; Humans ; Hydrogen Peroxide/metabolism ; Kidney/enzymology ; Liver/enzymology ; Reproducibility of Results ; Spectrophotometry, Ultraviolet/*methods ; }, abstract = {BACKGROUND: The details of a precise, accurate, and sensitive spectrophotometric method for measuring catalase activity are presented here. The assay was established for biological samples and depends on the rapid formation of a stable and colored carbonato-cobaltate (III) complex. Samples exhibiting catalase activity are incubated with hydrogen peroxide solution for 2 min prior to rapid mixing of the incubation enzymatic reaction mixture with cobalt-bicarbonate reagent, which assesses non-reacting hydrogen peroxide. Catalase activity is always directly proportional to the rate of dissociation of hydrogen peroxide. Hydrogen peroxide acts to oxidize cobalt (II) to cobalt (III) in the presence of bicarbonate ions; this process ends with the production of a carbonato-cobaltate (III) complex ([Co (CO3)3]Co). The formed end product has two maximum absorbance peaks: 440 nm and 640 nm. The 440-nm peak has been utilized for assessing catalase activity.

RESULTS: The catalase activity results of the current method for erythrocyte lysate homogenates were computationally identical to those of the dichromate method (r = 0.9950). The coefficient of variation was calculated to determine the imprecision of the current assay. The within-run and between-run results were 2.96 and 3.83%, respectively.

CONCLUSION: This method is appropriate for analyzing bacteria, red blood cells and liver and kidney tissue homogenates.}, } @article {pmid30075704, year = {2018}, author = {Fan, TP and Ting, HC and Yu, JK and Su, YH}, title = {Reiterative use of FGF signaling in mesoderm development during embryogenesis and metamorphosis in the hemichordate Ptychodera flava.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {120}, pmid = {30075704}, issn = {1471-2148}, support = {MOST-103-2311-B-001-030-MY3//Ministry of Science and Technology, Taiwan/International ; MOST-106-2321-B-001-039//Ministry of Science and Technology, Taiwan/International ; }, mesh = {Animals ; Chordata/*embryology/genetics/*growth & development ; Embryonic Development/*genetics ; Fibroblast Growth Factors/genetics/*metabolism ; Gene Expression Regulation, Developmental ; Larva/growth & development ; Ligands ; Mesoderm/*embryology/*metabolism ; Metamorphosis, Biological/*genetics ; Muscle Development/genetics ; Muscle Fibers, Skeletal/metabolism ; Receptors, Fibroblast Growth Factor/metabolism ; *Signal Transduction ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Mesoderm is generally considered to be a germ layer that is unique to Bilateria, and it develops into diverse tissues, including muscle, and in the case of vertebrates, the skeleton and notochord. Studies on various deuterostome animals have demonstrated that fibroblast growth factor (FGF) signaling is required for the formation of many mesodermal structures, such as vertebrate somites, from which muscles are differentiated, and muscles in sea urchin embryos, suggesting an ancient role of FGF signaling in muscle development. However, the formation of trunk muscles in invertebrate chordates is FGF-independent, leading to ambiguity about this ancient role in deuterostomes. To further understand the role of FGF signaling during deuterostome evolution, we investigated the development of mesodermal structures during embryogenesis and metamorphosis in Ptychodera flava, an indirect-developing hemichordate that has larval morphology similar to echinoderms and adult body features that are similar to chordates.

RESULTS: Here we show that genes encoding FGF ligands, FGF receptors and transcription factors that are known to be involved in mesoderm formation and myogenesis are expressed dynamically during embryogenesis and metamorphosis. FGF signaling at the early gastrula stage is required for the specification of the mesodermal cell fate in P. flava. The mesoderm cells are then differentiated stepwise into the hydroporic canal, the pharyngeal muscle and the muscle string; formation of the last two muscular structures are controlled by FGF signaling. Moreover, augmentation of FGF signaling during metamorphosis accelerated the process, facilitating the transformation from cilia-driven swimming larvae into muscle-driven worm-like juveniles.

CONCLUSIONS: Our data show that FGF signaling is required for mesoderm induction and myogenesis in the P. flava embryo, and it is reiteratively used for the morphological transition during metamorphosis. The dependence of muscle development on FGF signaling in both planktonic larvae and sand-burrowing worms supports its ancestral role in deuterostomes.}, } @article {pmid30075703, year = {2018}, author = {Zhong, S and Wang, J and Zhang, Q and Xu, H and Feng, J}, title = {CircPrimer: a software for annotating circRNAs and determining the specificity of circRNA primers.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {292}, pmid = {30075703}, issn = {1471-2105}, support = {81602551//The National Natural Science Foundation of China/ ; 2017YQL-10//Excellent Young Talents Fund Program of Higher Education Institutions of Anhui Province (CN)/ ; F201762//Jiangsu Provincial Women and Children Health Research Project/ ; 2016-WSW-086//Jiangsu Province six talent peak personal training project/ ; }, abstract = {BACKGROUND: Since circular RNAs (circRNAs) post-transcriptionally regulate gene expression, they have attracted increasing attention. However, there is no existing tool to annotate and extract spliced sequences for circRNAs and no tool to determine the specificity of circRNA primers.

RESULTS: In this study, we present circPrimer, which allows users to search, annotate, and visualize circRNAs. Additionally, circPrimer enables users to extract the spliced sequences and genomic sequences of any circRNA, including novel circRNAs. Furthermore, circPrimer help users to design primers for circRNAs and to determine the specificity of the circRNA primers.

CONCLUSIONS: CircPrimer is a user-friendly tool for exploring circRNAs that does not require special user skills.}, } @article {pmid30075702, year = {2018}, author = {Cai, W and Zhou, D and Wu, W and Tan, WL and Wang, J and Zhou, C and Lou, Y}, title = {MHC class II restricted neoantigen peptides predicted by clonal mutation analysis in lung adenocarcinoma patients: implications on prognostic immunological biomarker and vaccine design.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {582}, pmid = {30075702}, issn = {1471-2164}, support = {81570007//National Natural Science Foundation of China grant/ ; }, mesh = {Adenocarcinoma of Lung/*genetics/immunology ; Antigens, Neoplasm/immunology ; Biomarkers, Tumor/*genetics/metabolism ; DNA Mutational Analysis/*methods ; Databases, Genetic ; HLA-DRB1 Chains/*immunology ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Immunologic Tests ; Immunotherapy ; Peptides/*genetics/metabolism ; Sequence Analysis, DNA/methods ; }, abstract = {BACKGROUND: Mutant peptides presented by MHC (major histocompatibility complex) Class II in cancer are important targets for cancer immunotherapy. Both animal studies and clinical trials in cancer patients showed that CD4 T cells specific to tumor-derived mutant peptides are essential for the efficacy of immune checkpoint blockade therapy by PD1 antibody.

RESULTS: In this study, we analyzed the next generation sequencing data of 147 lung adenocarcinoma patients from The Cancer Genome Atlas and predicted neoantigens presented by MHC Class I and Class II molecules. We found 18,175 expressed clonal somatic mutations, with an average of 124 per patient. The presentation of mutant peptides by an HLA(human leukocyte antigen) Class II molecule, HLA DRB1, were predicted by NetMHCIIpan3.1. 8804 neo-peptides, including 375 strong binders and 8429 weak binders were found. For HLA DRB1*01:01, 54 strong binders and 896 weak binders were found. The most commonly mutated genes with predicted neo-antigens are KRAS, TTN, RYR2, MUC16, TP53, USH2A, ZFHX4, KEAP1, STK11, FAT3, NAV3 and EGFR.

CONCLUSIONS: Our results support the feasibility of discovering individualized HLA Class II presented mutant peptides as candidates for immunodiagnosis and immunotherapy of lung adenocarcinoma.}, } @article {pmid30075701, year = {2018}, author = {Bekpen, C and Xie, C and Tautz, D}, title = {Dealing with the adaptive immune system during de novo evolution of genes from intergenic sequences.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {121}, pmid = {30075701}, issn = {1471-2148}, support = {NewGenes - 322564//European Research Council/International ; }, mesh = {Adaptive Immunity/*genetics ; Animals ; Base Sequence ; Computer Simulation ; DNA, Intergenic/*genetics ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation ; Immune System/*immunology ; Mice ; Phylogeny ; RNA, Messenger/genetics/metabolism ; Transcriptome/genetics ; }, abstract = {BACKGROUND: The adaptive immune system of vertebrates has an extraordinary potential to sense and neutralize foreign antigens entering the body. De novo evolution of genes implies that the genome itself expresses novel antigens from intergenic sequences which could cause a problem with this immune system. Peptides from these novel proteins could be presented by the major histocompatibility complex (MHC) receptors to the cell surface and would be recognized as foreign. The respective cells would then be attacked and destroyed, or would cause inflammatory responses. Hence, de novo expressed peptides have to be introduced to the immune system as being self-peptides to avoid such autoimmune reactions. The regulation of the distinction between self and non-self starts during embryonic development, but continues late into adulthood. It is mostly mediated by specialized cells in the thymus, but can also be conveyed in peripheral tissues, such as the lymph nodes and the spleen. The self-antigens need to be exposed to the reactive T-cells, which requires the expression of the genes in the respective tissues. Since the initial activation of a promotor for new intergenic transcription of a de novo gene could occur in any tissue, we should expect that the evolutionary establishment of a de novo gene in animals with an adaptive immune system should also involve expression in at least one of the tissues that confer self-recognition.

RESULTS: We have studied this question by analyzing the transcriptomes of multiple tissues from young mice in three closely related natural populations of the house mouse (M. m. domesticus). We find that new intergenic transcription occurs indeed mostly in only a single tissue. When a second tissue becomes involved, thymus and spleen are significantly overrepresented.

CONCLUSIONS: We conclude that the inclusion of de novo transcripts in the processes for the induction of self-tolerance is indeed an important step in the evolution of functional de novo genes in vertebrates.}, } @article {pmid30075700, year = {2018}, author = {Li, R and Erpelding, JE and Stetina, SR}, title = {Genome-wide association study of Gossypium arboreum resistance to reniform nematode.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {52}, pmid = {30075700}, issn = {1471-2156}, abstract = {BACKGROUND: Reniform nematode (Rotylenchulus reniformis) has emerged as one of the most destructive root pathogens of upland cotton (Gossypium hirsutum) in the United States. Management of R. reniformis has been hindered by the lack of resistant G. hirsutum cultivars; however, resistance has been frequently identified in germplasm accessions from the G. arboreum collection. To determine the genetic basis of reniform nematode resistance, a genome-wide association study (GWAS) was performed using 246 G. arboreum germplasm accessions that were genotyped with 7220 single nucleotide polymorphic (SNP) sequence markers generated from genotyping-by-sequencing.

RESULTS: Fifteen SNPs representing 12 genomic loci distributed over eight chromosomes showed association with reniform nematode resistance. For 14 SNPs, major alleles were shown to be associated with resistance. From the 15 significantly associated SNPs, 146 genes containing or physically close to these loci were identified as putative reniform nematode resistance candidate genes. These genes are involved in a broad range of biological pathways, including plant innate immunity, transcriptional regulation, and redox reaction that may have a role in the expression of resistance. Eighteen of these genes corresponded to differentially expressed genes identified from G. hirsutum in response to reniform nematode infection.

CONCLUSIONS: The identification of multiple genomic loci associated with reniform nematode resistance would indicate that the G. arboreum collection is a significant resource of novel resistance genes. The significantly associated markers identified from this GWAS can be used for the development of molecular tools for breeding improved reniform nematode resistant upland cotton with resistance introgressed from G. arboreum. Additionally, a greater understanding of the molecular mechanisms of reniform nematode resistance can be determined through genetic structure and functional analyses of candidate genes, which will aid in the pyramiding of multiple resistance genes.}, } @article {pmid30075699, year = {2018}, author = {Krah, FS and Bässler, C and Heibl, C and Soghigian, J and Schaefer, H and Hibbett, DS}, title = {Evolutionary dynamics of host specialization in wood-decay fungi.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {119}, pmid = {30075699}, issn = {1471-2148}, support = {IOS-1456777//National Science Foundation/International ; Open Access Publishing//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Basidiomycota/classification/*physiology ; *Biological Evolution ; Cycadopsida/*microbiology ; Fruiting Bodies, Fungal/metabolism ; *Host-Pathogen Interactions ; Models, Biological ; Phylogeny ; Species Specificity ; Wood/*microbiology ; }, abstract = {BACKGROUND: The majority of wood decomposing fungi are mushroom-forming Agaricomycetes, which exhibit two main modes of plant cell wall decomposition: white rot, in which all plant cell wall components are degraded, including lignin, and brown rot, in which lignin is modified but not appreciably removed. Previous studies suggested that brown rot fungi tend to be specialists of gymnosperm hosts and that brown rot promotes gymnosperm specialization. However, these hypotheses were based on analyses of limited datasets of Agaricomycetes. Overcoming this limitation, we used a phylogeny with 1157 species integrating available sequences, assembled decay mode characters from the literature, and coded host specialization using the newly developed R package, rusda.

RESULTS: We found that most brown rot fungi are generalists or gymnosperm specialists, whereas most white rot fungi are angiosperm specialists. A six-state model of the evolution of host specialization revealed high transition rates between generalism and specialization in both decay modes. However, while white rot lineages switched most frequently to angiosperm specialists, brown rot lineages switched most frequently to generalism. A time-calibrated phylogeny revealed that Agaricomycetes is older than the flowering plants but many of the large clades originated after the diversification of the angiosperms in the Cretaceous.

CONCLUSIONS: Our results challenge the current view that brown rot fungi are primarily gymnosperm specialists and reveal intensive white rot specialization to angiosperm hosts. We thus suggest that brown rot associated convergent loss of lignocellulose degrading enzymes was correlated with host generalism, rather than gymnosperm specialism. A likelihood model of host specialization evolution together with a time-calibrated phylogeny further suggests that the rise of the angiosperms opened a new mega-niche for wood-decay fungi, which was exploited particularly well by white rot lineages.}, } @article {pmid30075698, year = {2018}, author = {Orr, RJS and Zhao, S and Klaveness, D and Yabuki, A and Ikeda, K and Watanabe, MM and Shalchian-Tabrizi, K}, title = {Correction to: Enigmatic Diphyllatea eukaryotes: culturing and targeted PacBio RS amplicon sequencing reveals a higher order taxonomic diversity and global distribution.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {118}, pmid = {30075698}, issn = {1471-2148}, abstract = {In the original publication of this article [1] there was an error in an author name. In this correction article the correct and incorrect name are indicated.}, } @article {pmid30075296, year = {2018}, author = {Smissen, PJ and Rowe, KC}, title = {Repeated biome transitions in the evolution of Australian rodents.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {182-191}, doi = {10.1016/j.ympev.2018.07.015}, pmid = {30075296}, issn = {1095-9513}, abstract = {Transitions between disparate biomes (e.g. arid and mesic) are expected to be rare, but few systems provide the taxonomic sampling and geographic scope to test these expectations. The Pseudomys division comprising 5 genera and 41 historically extant species are the most diverse group of rodents to evolve from a single colonisation of Australia and are widely distributed across biomes. With a species-level phylogeny we show that repeated biome transitions were required to achieve the distributions of extant taxa in this group with half of all transitions originating from the arid biome. Transitions to the monsoon and arid biomes occurred early, but transition to the temperate mesic biome occurred up to 2 MY later. Early evolving genera remained primarily restricted to a single biome with few transitions among biomes. In contrast, transitions between biomes were associated with most speciation events in a phylogenetically-nested clade of the genus Pseudomys. Our results suggest that, at the broad environmental scale of biome transitions, evolutionarily labile niche divergence can evolve in lineages descended from niche conservative taxa.}, } @article {pmid30075108, year = {2018}, author = {Wiegering, A and Rüther, U and Gerhardt, C}, title = {The ciliary protein Rpgrip1l in development and disease.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {60-68}, doi = {10.1016/j.ydbio.2018.07.024}, pmid = {30075108}, issn = {1095-564X}, mesh = {Adaptor Proteins, Signal Transducing/*genetics/*metabolism ; Animals ; Cilia/genetics/metabolism ; Disease Models, Animal ; Humans ; Mutation ; Proteostasis ; Signal Transduction ; }, abstract = {RPGRIP1L is an evolutionary highly conserved gene encoding a protein that localises at the transition zone of primary cilia. Mutations in RPGRIP1L result in ciliopathies, severe human diseases caused by dysfunctional cilia. Patients with mutations in this gene often suffer from an impaired development of not only one but various organs. To elucidate the function of Rpgrip1l in human development and the mechanisms underlying ciliopathies, different model organisms are used. In this review article, we summarise the findings of these investigations comprising novel functions of Rpgrip1l and the most promising therapeutic approaches.}, } @article {pmid30075055, year = {2018}, author = {Vijendravarma, RK}, title = {Experimental evolution demonstrates evolvability of preferential nutrient allocation to competing traits in response to chronic malnutrition.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1743-1749}, doi = {10.1111/jeb.13359}, pmid = {30075055}, issn = {1420-9101}, support = {31003A_143939//Swiss National Science Foundation/ ; }, abstract = {Investigating the evolutionary origins of disease vulnerability is an important aspect of evolutionary medicine that strongly complements our current understanding on proximate causes of disease. Life-history trade-offs mediated through evolutionary changes in resource allocation strategies could be one possible explanation to why suboptimal traits that leave bodies vulnerable to disease exist. For example, Drosophila melanogaster populations experimentally evolved to tolerate chronic larval malnutrition succumb to intestinal infection despite eliciting a competent immune response, owing to the loss of their intestinal integrity. Here, I test whether evolved changes in resource allocation underlies this trade-off, by assaying preferential allocation of dietary protein towards growth and tissue repair in the same populations. Using two phenotypic traits, regeneration of intestinal epithelium post-pathogenic infection and body weight, I show that in accordance with the dynamic energy budget theory (DEB) dietary protein acquired during the larval phase is allocated to both growth and adult tissue repair. Furthermore, by altering the ratio of protein and carbohydrates in the larval diets I demonstrate that in comparison with the control populations, the evolved (selected) populations differ in their protein allocation strategy towards these two traits. While the control populations stored away excess protein for tissue repair, the selected populations invested it towards immediate increase in body weight rather than towards an unanticipated tissue damage. Thus, I show how macronutrient availability and their allocation between traits can alter resistance, and provide empirical evidence that supports the 'mismatch hypothesis', wherein vulnerability to disease is proposed to stem from the differences between ancestral and current environment.}, } @article {pmid30075053, year = {2018}, author = {Tung, S and Mishra, A and Gogna, N and Aamir Sadiq, M and Shreenidhi, PM and Shree Sruti, VR and Dorai, K and Dey, S}, title = {Evolution of dispersal syndrome and its corresponding metabolomic changes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1890-1903}, doi = {10.1111/evo.13560}, pmid = {30075053}, issn = {1558-5646}, support = {#EMR/2014/000476//Science and Engineering Research Board/ ; //Council of Scientific and Industrial Research, Government of India/ ; //INSPIRE fellowship of Department of Science and Technology, Government of India/ ; //GE Foundation Scholar Leaders Program/ ; //IISER Mohali institutional fellowship/ ; }, abstract = {Dispersal is one of the strategies for organisms to deal with climate change and habitat degradation. Therefore, investigating the effects of dispersal evolution on natural populations is of considerable interest to ecologists and conservation biologists. Although it is known that dispersal itself can evolve due to selection, the behavioral, life-history and metabolic consequences of dispersal evolution are not well understood. Here, we explore these issues by subjecting four outbred laboratory populations of Drosophila melanogaster to selection for increased dispersal. The dispersal-selected populations had similar values of body size, fecundity, and longevity as the nonselected lines (controls), but evolved significantly greater locomotor activity, exploratory tendency, and aggression. Untargeted metabolomic fingerprinting through NMR spectroscopy suggested that the selected flies evolved elevated cellular respiration characterized by greater amounts of glucose, AMP, and NAD. Concurrent evolution of higher level of Octopamine and other neurotransmitters indicate a possible mechanism for the behavioral changes in the selected lines. We discuss the generalizability of our findings in the context of observations from natural populations. To the best of our knowledge, this is the first report of the evolution of metabolome due to selection for dispersal and its connection to dispersal syndrome evolution.}, } @article {pmid30074816, year = {2018}, author = {Yamashita, YM and Inaba, M and Buszczak, M}, title = {Specialized Intercellular Communications via Cytonemes and Nanotubes.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {59-84}, doi = {10.1146/annurev-cellbio-100617-062932}, pmid = {30074816}, issn = {1530-8995}, abstract = {In recent years, thin membrane protrusions such as cytonemes and tunneling nanotubes have emerged as a novel mechanism of intercellular communication. Protrusion-based cellular interactions allow for specific communication between participating cells and have a distinct spectrum of advantages compared to secretion- and diffusion-based intercellular communication. Identification of protrusion-based signaling in diverse systems suggests that this mechanism is a ubiquitous and prevailing means of communication employed by many cell types. Moreover, accumulating evidence indicates that protrusion-based intercellular communication is often involved in pathogenesis, including cancers and infections. Here we review our current understanding of protrusion-based intercellular communication.}, } @article {pmid30074670, year = {2018}, author = {Endo, Y and Kamei, KI and Inoue-Murayama, M}, title = {Genetic signatures of lipid metabolism evolution in Cetacea since the divergence from terrestrial ancestor.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1655-1665}, doi = {10.1111/jeb.13361}, pmid = {30074670}, issn = {1420-9101}, support = {16K14660//Japan Society for the Promotion of Science/ ; 25118005//Japan Society for the Promotion of Science/ ; //Kyoto University Supporting program for interaction-based initiative team studies (SPIRITS)/ ; //World Premier International Research Centre Initiative (WPI)/ ; //MEXT/ ; }, abstract = {In mammalian evolutionary history, Cetacea (whales, dolphins and porpoises) achieved astonishing success by adapting to an aquatic environment. One unique characteristic of cetaceans, contributing to this adaptive success, is efficient lipid utilization. Here, we report a comparative genetic analysis of five aquatic and five terrestrial Cetartiodactyla species using 144 genes associated with lipid metabolism. Mutation ratio (dN /dS), amino acid substitution in functional domains and metabolic pathways were evaluated using branch-site model in PAML, Pfam and KEGG, respectively. Our tests detected 20 positively selected genes in Cetacea compared to 11 in Bovidae with little overlap between the lineages. We identified lineage-specific patterns of amino acid substitutions and functional domains that were mutually exclusive between cetaceans and bovids, supporting divergent evolution of lipid metabolism since the divergence of these taxa from a common ancestor. Moreover, a pathway analysis showed that the identified genes in cetaceans were associated with lipid digestion, lipid storage and energy-producing pathways. This study emphasizes the evolutionary context of lipid metabolism modification of cetaceans and provides a foundation for future studies of elucidating the adapted biological mechanisms of cetacean lipid metabolism and a framework for incorporating ecological context into studies aimed at investigating adaptive evolution.}, } @article {pmid30074666, year = {2018}, author = {Svanfeldt, K and Monro, K and Marshall, DJ}, title = {Resources mediate selection on module longevity in the field.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1666-1674}, doi = {10.1111/jeb.13362}, pmid = {30074666}, issn = {1420-9101}, support = {//ARC/ ; }, abstract = {The life histories of modular organisms are complicated, where selection and optimization can occur at both organismal and modular levels. At a modular level, growth, reproduction and death can occur in one module, independently of others. Across modular groups, there are no formal investigations of selection on module longevity. We used two field experiments to test whether selection acts on module longevity in a sessile marine invertebrate and whether selection varies across successional gradients and resource regimes. We found that selection does act on module longevity and that the strength of selection varies with environmental conditions. In environments where interspecific competition is high, selection favours colonies with longer zooid (module) longevity for colonies that initially received high levels of maternal investment. In environments where food availability is high and flow rate is low, selection also favours colonies with longer zooid longevity. These patterns of selection provide partial support for module longevity theory developed for plants. Nevertheless, that selection on module longevity is so context-dependent suggests that variation in module longevity is likely to be maintained in this system.}, } @article {pmid30074655, year = {2018}, author = {Firman, RC and Garcia-Gonzalez, F and Simmons, LW and André, GI}, title = {A competitive environment influences sperm production, but not testes tissue composition, in house mice.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1647-1654}, doi = {10.1111/jeb.13360}, pmid = {30074655}, issn = {1420-9101}, support = {DE140100476//Australian Research Council/ ; DP1601000797//Australian Research Council/ ; CGL2012-34685//The Spanish Ministry of Economy/ ; CGL2016-76173-P//The Spanish Ministry of Economy/ ; }, abstract = {Due to the physiological cost of sperm production, males are expected to be prudent in their expenditure and adjust their investment according to current social conditions. Strategic adjustments in sperm expenditure during development can be made via changes in testes size, sperm production rates or testes tissue composition. Here, using house mice, we test the hypothesis that elevated sperm production is driven by a plastic response in the spatial organization of the testes. We reared males under different social conditions (competitive vs. noncompetitive) and quantified sperm number and the proportion of sperm-producing tissue within the testes. Further, because sperm quality is a critical determinant of competitive fertilization success, we used computer-assisted sperm analysis to quantify six sperm motility traits. Our investigation revealed that males reared in an environment with a perceived risk of reproductive competition produced more sperm in the absence of changes in testes morphology. We discuss this result in relation to fixed and flexible phenotypically plastic responses to future competitive conditions, and conclude that adaptive adjustments in sperm number in response to the social environment are likely attributable to variation in sperm production rate. Further, we found no difference in in vitro sperm motility parameters among males from the different social environment regimes. Overall, this investigation improves our understanding of the mechanisms of male plastic responses to reproductive competition experienced during sexual development.}, } @article {pmid30073946, year = {2018}, author = {Liu, Y and Du, J and Lai, Q and Zeng, R and Ye, D and Xu, J and Shao, Z}, title = {Corrigendum: Proposal of nine novel species of the Bacillus cereus group.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2706}, doi = {10.1099/ijsem.0.002902}, pmid = {30073946}, issn = {1466-5034}, } @article {pmid30073945, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 5, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2413-2415}, doi = {10.1099/ijsem.0.002798}, pmid = {30073945}, issn = {1466-5034}, } @article {pmid30073752, year = {2018}, author = {Andersson, M and Åhlund, M and Waldeck, P}, title = {Brood parasitism, relatedness and sociality: a kinship role in female reproductive tactics.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12455}, pmid = {30073752}, issn = {1469-185X}, abstract = {Conspecific brood parasitism (CBP) is a reproductive tactic in which parasitic females lay eggs in nests of other females of the same species that then raise the joint brood. Parasites benefit by increased reproduction, without costs of parental care for the parasitic eggs. CBP occurs in many egg-laying animals, among birds most often in species with large clutches and self-feeding young: two major factors facilitating successful parasitism. CBP is particularly common in waterfowl (Anatidae), a group with female-biased natal philopatry and locally related females. Theory suggests that relatedness between host and parasite can lead to inclusive fitness benefits for both, but if host costs are high, parasites should instead target unrelated females. Pairwise relatedness (r) in host-parasite (h-p) pairs of females has been estimated using molecular genetic methods in seven waterfowl (10 studies). In many h-p pairs, the two females were unrelated (with low r, near the local population mean). However, close relatives (r = 0.5) were over-represented in h-p pairs, which in all 10 studies had higher mean relatedness than other females. In one species where this was studied, h-p relatedness was higher than between nesting close neighbours, and hosts parasitized by non-relatives aggressively rejected other females. In another species, birth nest-mates (mother-daughters, sisters) associated in the breeding area as adults, and became h-p pairs more often than expected by chance. These and other results point to recognition of birth nest-mates and perhaps other close relatives. For small to medium host clutch sizes, addition of a few parasitic eggs need not reduce host offspring success. Estimates in two species suggest that hosts can then gain inclusive fitness if parasitized by relatives. Other evidence of female cooperation is incubation by old eider Somateria mollissima females of clutches laid by their relatives, and merging and joint care of broods of young. Merging females tended to be more closely related. Eiders associate with kin in many situations, and in some geese and swans, related females may associate over many years. Recent genetic evidence shows that also New World quails (Odontophoridae) have female-biased natal philopatry, CBP and brood merging, inviting further study and comparison with waterfowl. Kin-related parasitism also occurs in some insects, with revealing parallels and differences compared to birds. In hemipteran bugs, receiving extra eggs is beneficial for hosts by diluting offspring predation. In eggplant lace bugs Gargaphia solani, host and parasite are closely related, and kin selection favours egg donation to related females. Further studies of kinship in CBP, brood merging and other contexts can test if some of these species are socially more advanced than presently known.}, } @article {pmid30073746, year = {2018}, author = {Nirwane, A and Yao, Y}, title = {Laminins and their receptors in the CNS.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12454}, pmid = {30073746}, issn = {1469-185X}, abstract = {Laminin, an extracellular matrix protein, is widely expressed in the central nervous system (CNS). By interacting with integrin and non-integrin receptors, laminin exerts a large variety of important functions in the CNS in both physiological and pathological conditions. Due to the existence of many laminin isoforms and their differential expression in various cell types in the CNS, the exact functions of each individual laminin molecule in CNS development and homeostasis remain largely unclear. In this review, we first briefly introduce the structure and biochemistry of laminins and their receptors. Next, the dynamic expression of laminins and their receptors in the CNS during both development and in adulthood is summarized in a cell-type-specific manner, which allows appreciation of their functional redundancy/compensation. Furthermore, we discuss the biological functions of laminins and their receptors in CNS development, blood-brain barrier (BBB) maintenance, neurodegeneration, stroke, and neuroinflammation. Last, key challenges and potential future research directions are summarized and discussed. Our goals are to provide a synthetic review to stimulate future studies and promote the formation of new ideas/hypotheses and new lines of research in this field.}, } @article {pmid30073082, year = {2018}, author = {Elbroch, LM and Marescot, L and Quigley, H and Craighead, D and Wittmer, HU}, title = {Multiple anthropogenic interventions drive puma survival following wolf recovery in the Greater Yellowstone Ecosystem.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7236-7245}, pmid = {30073082}, issn = {2045-7758}, abstract = {Humans are primary drivers of declining abundances and extirpation of large carnivores worldwide. Management interventions to restore biodiversity patterns, however, include carnivore reintroductions, despite the many unresolved ecological consequences associated with such efforts. Using multistate capture-mark-recapture models, we explored age-specific survival and cause-specific mortality rates for 134 pumas (Puma concolor) monitored in the Greater Yellowstone Ecosystem during gray wolf (Canis lupus) recovery. We identified two top models explaining differences in puma survivorship, and our results suggested three management interventions (unsustainable puma hunting, reduction in a primary prey, and reintroduction of a dominant competitor) have unintentionally impacted puma survival. Specifically, puma survival across age classes was lower in the 6-month hunting season than the 6-month nonhunting season; human-caused mortality rates for juveniles and adults, and predation rates on puma kittens, were higher in the hunting season. Predation on puma kittens, and starvation rates for all pumas, also increased as managers reduced elk (Cervus elaphus) abundance in the system, highlighting direct and indirect effects of competition between recovering wolves and pumas over prey. Our results emphasize the importance of understanding the synergistic effects of existing management strategies and the recovery of large, dominant carnivores to effectively conserve subordinate, hunted carnivores in human-dominated landscapes.}, } @article {pmid30073081, year = {2018}, author = {Oguntuase, BG and Ogunjemite, BG and Meisel, RP}, title = {Morphometric and genetic differentiation among populations of flat-headed cusimanse (Crossarchus platycephalus) in Nigeria.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7228-7235}, pmid = {30073081}, issn = {2045-7758}, abstract = {Geographic barriers can partition genetic diversity among populations and drive evolutionary divergence between populations, promoting the speciation process and affecting conservation goals. We integrated morphological and genomic data to assess the distribution of variation in the flat-headed cusimanse (Crossarchus platycephalus), a species of least conservation concern, on either side of the River Niger in Nigeria. Ecological disturbances affect the conservation status of many other animals in this region. The two populations were differentiated in the snout and fore limbs, with greater morphological diversity in the western population. We used Restriction site Associated DNA sequencing (RAD-seq) and identified two genotypic clusters in a STRUCTURE analysis. Individuals from the eastern population are almost entirely assigned to one cluster, whereas genotypes from the western population are a mixture of the two clusters. The population from west of the River Niger also had higher heterozygosity. The morphological and population genetic data are therefore in agreement that the population from west of the River Niger is more diverse than the eastern population, and the eastern population contains a subset of the genetic variation found in the western population. Our results demonstrate that combining morphological and genotypic measures of diversity can provide a congruent picture of the distribution of intraspecific variation. The results also suggest that future work should explore the role of the River Niger as a natural barrier to migration in Nigeria.}, } @article {pmid30073080, year = {2018}, author = {Belgrad, BA and Griffen, BD}, title = {Personality interacts with habitat quality to govern individual mortality and dispersal patterns.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7216-7227}, pmid = {30073080}, issn = {2045-7758}, abstract = {Individual phenotypic differences are increasingly recognized as key drivers of ecological processes. However, studies examining the relative importance of these differences in comparison with environmental factors or how individual phenotype interacts across different environmental contexts remain lacking. We performed two field experiments to assess the concurrent roles of personality differences and habitat quality in mediating individual mortality and dispersal. We quantified the predator avoidance response of mud crabs, Panopeus herbstii, collected from low- and high-quality oyster reefs and measured crab loss in a caging experiment. We simultaneously measured the distance crabs traveled as well as the stability of personalities across reef quality in a separate reciprocal transplant experiment. Habitat quality was the primary determinant of crab loss, although the distance crabs traveled was governed by personality which interacted with habitat quality to control the fate of crabs. Here, crabs on low-quality reefs rapidly emigrated, starting with the boldest individuals, and experienced modest levels of predation regardless of personality. In contrast, both bold and shy crabs would remain on high-quality reefs for months where bolder individuals experienced higher predation risk. These findings suggest that personalities could produce vastly different population dynamics across habitat quality and govern community responses to habitat degradation.}, } @article {pmid30073079, year = {2018}, author = {Phillips, P and Swanson, BJ}, title = {A genetic analysis of dragonfly population structure.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7206-7215}, pmid = {30073079}, issn = {2045-7758}, abstract = {Dragonflies reside in both aquatic and terrestrial environments, depending on their life stage, necessitating the conservation of drastically different habitats; however, little is understood about how nymph and adult dragonflies function as metapopulations within connected habitat. We used genetic techniques to examine nymphs and adults within a single metapopulation both spatially and temporally to better understand metapopulation structure and the processes that might influence said structure. We sampled 97 nymphs and 149 adult Sympetrum obtrusum from eight locations, four aquatic, and four terrestrial, at the Pierce Cedar Creek Institute in Southwest Michigan over two summers. We performed AFLP genetic analysis and used the Bayesian analysis program STRUCTURE to detect genetic clusters from sampled individuals. STRUCTURE detected k = u4 populations, in which nymphs and adults from the same locations collected in different years did not necessarily fall into the same clusters. We also evaluated grouping using the statistical clustering analyses NMDS and MRPP. The results of these confirmed findings from STRUCTURE and emphasized differences between adults collected in 2012 and all other generations. These results suggest that both dispersal and a temporal cycle of emergence of nymphs from unique clusters every other year could be influential in structuring dragonfly populations, although our methods were not able to fully distinguish the influences of either force. This study provides a better understanding of local dragonfly metapopulation structure and provides a starting point for future studies to investigate the spatial and temporal mechanisms controlling metapopulation structure. The results of the study should prove informative for managers working to preserve genetic diversity in connected dragonfly metapopulations, especially in the face of increasing anthropogenic landscape changes.}, } @article {pmid30073078, year = {2018}, author = {Tan, SL and Luo, YH and Hollingsworth, PM and Burgess, KS and Xu, K and Li, DZ and Gao, LM}, title = {DNA barcoding herbaceous and woody plant species at a subalpine forest dynamics plot in Southwest China.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7195-7205}, pmid = {30073078}, issn = {2045-7758}, abstract = {Although DNA barcoding has been widely used to identify plant species composition in temperate and tropical ecosystems, relatively few studies have used DNA barcodes to document both herbaceous and woody components of forest plot. A total of 201 species (72 woody species and 129 herbaceous species) representing 135 genera distributed across 64 families of seed plants were collected in a 25 ha CForBio subalpine forest dynamics plot. In total, 491 specimens were screened for three DNA regions of the chloroplast genome (rbcL, matK, and trnH-psbA) as well as the internal transcribed spacers (ITS) of nuclear ribosomal DNA. We quantified species resolution for each barcode separately or in combination using a ML tree-based method. Amplification and sequencing success were highest for rbcL, followed by trnH-psbA, which performed better than ITS and matK. The rbcL + ITS barcode had slightly higher species resolution rates (88.60%) compared with rbcL + matK (86.60%) and rbcL + trnH-psbA (86.01%). The addition of trnH-psbA or ITS to the rbcL + matK barcode only marginally increased species resolution rates, although in combination the four barcodes had the highest discriminatory power (90.21%). The situations where DNA barcodes did not discriminate among species were typically associated with higher numbers of co-occurring con-generic species. In addition, herbaceous species were much better resolved than woody species. Our study represents one of the first applications of DNA barcodes in a subalpine forest dynamics plot and contributes to our understanding of patterns of genetic divergence among woody and herbaceous plant species.}, } @article {pmid30073077, year = {2018}, author = {Menegat, A and Milberg, P and Nilsson, ATS and Andersson, L and Vico, G}, title = {Soil water potential and temperature sum during reproductive growth control seed dormancy in Alopecurus myosuroides Huds.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7186-7194}, pmid = {30073077}, issn = {2045-7758}, abstract = {The sustainable management of unwanted vegetation in agricultural fields through integrated weed control strategies requires detailed knowledge about the maternal formation of primary seed dormancy, to support the prediction of seedling emergence dynamics. This knowledge is decisive for the timing of crop sowing and nonchemical weed control measures. Studies in controlled environments have already demonstrated that thermal conditions and, to some extent, water availability during seed set and maturation has an impact on the level of dormancy. However, it is still unclear if this applies also under field conditions, where environmental stressors and their timing are more variable. We address this question for Alopecurus myosuroides in south-western Sweden. We quantified the effects of cumulated temperature and precipitation as well as soil water potential during the reproductive growth phase of A myosuroides on primary seed dormancy under field conditions. Empirical models differing in focal time intervals and, in case of soil water potential, focal soil depths were compared regarding their predictive power. The highest predictive power for the level of primary dormancy of A. myosuroides seeds was found for a two-factorial linear model containing air temperature sum between 0 and 7 days before peak seed shedding as well as the number of days with soil water potential below field capacity between 7 and 35 days before peak seed shedding. For soil water potential, it was found that only the top 10 cm soil layer is of relevance, which is in line with the shallow root architecture of A. myosuroides. We conclude that for this species the level of dormancy depends on the magnitude and timing of temperature and water availability during the reproductive growth phase. Water availability appears to be more important during maternal environmental perception and temperature during zygotic environmental perception.}, } @article {pmid30073076, year = {2018}, author = {Wiley, EM and Ridley, AR}, title = {The benefits of pair bond tenure in the cooperatively breeding pied babbler (Turdoides bicolor).}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7178-7185}, pmid = {30073076}, issn = {2045-7758}, abstract = {The benefits of stable pair bonds (that persist between breeding attempts) have been well described, but are relatively less well known in cooperatively breeding species. If pair bonds are beneficial, then it is possible that the bond between the behaviorally and socially dominant pair may influence factors such as reproductive success and group stability in cooperative species. Here, we used long-term data to investigate the relationships between pair bond tenure, reproductive success, and group stability in the cooperatively breeding pied babbler (Turdoides bicolor). Pair bond tenure positively influenced both the number of offspring recruited annually per pair and total reproductive success (over entire pair bond duration), indicating that pair bond tenure has an important influence on reproductive success. The likelihood of immigration into the group was lower for groups containing a bonded pair with long tenure, indicating that the duration of pair bonds may impact group stability. These findings suggest that pair tenure, a hitherto relatively unexplored factor in cooperative species, may have an important influence on group dynamics.}, } @article {pmid30073075, year = {2018}, author = {Stubbs, RL and Soltis, DE and Cellinese, N}, title = {The future of cold-adapted plants in changing climates: Micranthes (Saxifragaceae) as a case study.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7164-7177}, pmid = {30073075}, issn = {2045-7758}, abstract = {Research has shown species undergoing range contractions and/or northward and higher elevational movements as a result of changing climates. Here, we evaluate how the distribution of a group of cold-adapted plant species with similar evolutionary histories changes in response to warming climates. We selected 29 species of Micranthes (Saxifragaceae) representing the mountain and Arctic biomes of the Northern Hemisphere. For this analysis, 24,755 data points were input into ecological niche models to assess both present fundamental niches and predicted future ranges under climate change scenarios. Comparisons were made across the Northern Hemisphere between all cold-adapted Micranthes, including Arctic species, montane species, and species defined as narrow endemics. Under future climate change models, 72% of the species would occupy smaller geographical areas than at present. This loss of habitat is most pronounced in Arctic species in general, but is also prevalent in species restricted to higher elevations in mountains. Additionally, narrowly endemic species restricted to high elevations were more susceptible to habitat loss than those species found at lower elevations. Using a large dataset and modeling habitat suitability at a global scale, our results empirically model the threats to cold-adapted species as a result of warming climates. Although Arctic and alpine biomes share many underlying climate similarities, such as cold and short growing seasons, our results confirm that species in these climates have varied responses to climate change and that key abiotic variables differ between these two habitats.}, } @article {pmid30073074, year = {2018}, author = {Randler, C and Kalb, N}, title = {Distance and size matters: A comparison of six wildlife camera traps and their usefulness for wild birds.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7151-7163}, pmid = {30073074}, issn = {2045-7758}, abstract = {Camera traps are increasingly used in ecological research. However, tests of their performance are scarce. It is already known from previous work that camera traps frequently fail to capture visits by animals. This can lead to a misinterpretation of ecological results such as density estimates or predation events. While previous work is mainly based on mammals, for birds, no data about if and how camera traps can be successfully used to estimate species diversity or density are available. Hence, the goal of our study was an empirical validation of six different camera traps in the field. We observed a total number of N = 4567 events (independent visits of a bird) in 100 different sessions from March 2017 until January 2018 while camera traps were deployed. In addition, N = 641 events are based on a comparison of the two close-up camera traps especially designed for birds. These events were all directly observed by the authors. Thus, the cameras can be compared against the human observer. To give an overall assessment and a more generalizable result, we combined the data from the six camera traps and showed that bird size category (effect size = 0.207) and distance (effect size = 0.132) are the most important predictors for a successful trigger. Also, temperature had a small effect, and flock size had an impact with larger flocks being captured more often. The approach of the bird, whether it approached the camera frontally or laterally had no influence. In Table 8, we give some recommendations, based on our results, at which distances camera traps should be placed to get a 25%, 50%, and 75% capture rate for a given bird size.}, } @article {pmid30073073, year = {2018}, author = {Mašková, T and Herben, T}, title = {Root:shoot ratio in developing seedlings: How seedlings change their allocation in response to seed mass and ambient nutrient supply.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7143-7150}, pmid = {30073073}, issn = {2045-7758}, abstract = {Root:shoot (R:S) biomass partitioning is one of the keys to the plants' ability to compensate for limiting resources in the environment and thus to survive and succeed in competition. In adult plants, it can vary in response to many factors, such as nutrient availability in the soil or reserves in the roots from the previous season. The question remains whether, at the interspecific level, reserves in seeds can affect seedlings' R:S ratio in a similar way. Proper allocation to resource-acquiring organs is enormously important for seedlings and is likely to determine their survival and further success. Therefore, we investigated the effect of seed mass on seedling R:S biomass partitioning and its interaction with nutrient supply in the substrate. We measured seedling biomass partitioning under two different nutrient treatments after 2, 4, 6, and 12 weeks for seventeen species differing in seed mass and covering. We used phylogenetically informed analysis to determine the independent influence of seed mass on seedling biomass partitioning. We found consistently lower R:S ratios in seedlings with higher seed mass. Expectedly, R:S was also lower with higher substrate nutrient supply, but substrate nutrient supply had a bigger effect on R:S ratio for species with higher seed mass. These findings point to the importance of seed reserves for the usage of soil resources. Generally, R:S ratio decreased over time and, similarly to the effect of substrate nutrients, R:S ratio decreased faster for large-seeded species. We show that the seed mass determines the allocation patterns into new resource-acquiring organs during seedling development. Large-seeded species are more flexible in soil nutrient use. It is likely that faster development of shoots provides large-seeded species with the key advantage in asymmetric above-ground competition, and that this could constitute one of the selective factors for optimum seed mass.}, } @article {pmid30073072, year = {2018}, author = {Salgado-Roa, FC and Pardo-Diaz, C and Lasso, E and Arias, CF and Solferini, VN and Salazar, C}, title = {Gene flow and Andean uplift shape the diversification of Gasteracantha cancriformis (Araneae: Araneidae) in Northern South America.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7131-7142}, pmid = {30073072}, issn = {2045-7758}, abstract = {The Andean uplift has played a major role in shaping the current Neotropical biodiversity. However, in arthropods other than butterflies, little is known about how this geographic barrier has impacted species historical diversification. Here, we examined the phylogeography of the widespread color polymorphic spider Gasteracantha cancriformis to evaluate the effect of the northern Andean uplift on its divergence and assess whether its diversification occurred in the presence of gene flow. We inferred phylogenetic relationships and divergence times in G. cancriformis using mitochondrial and nuclear data from 105 individuals in northern South America. Genetic diversity, divergence, and population structure were quantified. We also compared multiple demographic scenarios for this species using a model-based approach (phrapl) to determine divergence with or without gene flow. At last, we evaluated the association between genetic variation and color polymorphism. Both nuclear and mitochondrial data supported two well-differentiated clades, which correspond to populations occurring on opposite sides of the Eastern cordillera of the Colombian Andes. The final uplift of this cordillera was identified as the most likely force that shaped the diversification of G. cancriformis in northern South America, resulting in a cis- and trans-Andean phylogeographic structure for the species. We also found shared genetic variation between the cis- and trans-Andean clades, which is better explained by a scenario of historical divergence in the face of gene flow. This has been likely facilitated by the presence of low-elevation passes across the Eastern Colombian cordillera. Our work constitutes the first example in which the Andean uplift coupled with gene flow influenced the evolutionary history of an arachnid lineage.}, } @article {pmid30073071, year = {2018}, author = {Cottingham, A and Huang, P and Hipsey, MR and Hall, NG and Ashworth, E and Williams, J and Potter, IC}, title = {Growth, condition, and maturity schedules of an estuarine fish species change in estuaries following increased hypoxia due to climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7111-7130}, pmid = {30073071}, issn = {2045-7758}, abstract = {Understanding challenges posed by climate change to estuaries and their faunas remains a high priority for managing these systems and their communities. Freshwater discharge into a range of estuary types in south-western Australia between 1990 and 2015 is shown to be related to rainfall. This largely accounts for decreases in discharge in this microtidal region being more pronounced on the west coast than south coast, where rainfall decline was less. Results of an oxygen-balance model imply that, as demonstrated by empirical data for the Swan River Estuary, declines in discharge into a range of estuary types would be accompanied by increases in the extent of hypoxia. In 2013-15, growth and body condition of the teleost Acanthopagrus butcheri varied markedly among three permanently open, one intermittently-open, one seasonally-closed and one normally-closed estuary, with average time taken by females to reach the minimum legal length (MLL) of 250 mm ranging from 3.6 to 17.7 years. It is proposed that, in a given restricted period, these inter-estuary variations in biological characteristics are related more to differences in factors, such as food resources and density, than to temperature and salinity. The biological characteristics of A. butcheri in the four estuaries, for which there are historical data, changed markedly between 1993-96 and 2013-15. Growth of both sexes, and also body condition in all but the normally-closed estuary, declined, with females taking between 1.7 and 2.9 times longer to attain the MLL. Irrespective of period, body condition, and growth are positively related. Age at maturity typically increased between periods, but length at maturity declined only in the estuary in which growth was greatest. The plasticity of the biological characteristics of A. butcheri, allied with confinement to its natal estuary and ability to tolerate a wide range of environmental conditions, makes this sparid and comparable species excellent subjects for assessing estuarine "health."}, } @article {pmid30073070, year = {2018}, author = {Brock, CD and Rennison, D and Veen, T and Bolnick, DI}, title = {Opsin expression predicts male nuptial color in threespine stickleback.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7094-7102}, pmid = {30073070}, issn = {2045-7758}, abstract = {Theoretical models of sexual selection suggest that male courtship signals can evolve through the build-up of genetic correlations between the male signal and female preference. When preference is mediated via increased sensitivity of the signal characteristics, correlations between male signal and perception/sensitivity are expected. When signal expression is limited to males, we would expect to find signal-sensitivity correlations in males. Here, we document such a correlation within a breeding population of threespine stickleback mediated by differences in opsin expression. Males with redder nuptial coloration express more long-wavelength-sensitive (LWS) opsin, making them more sensitive to orange and red. This correlation is not an artifact of shared tuning to the optical microhabitat. Such correlations are an essential feature of many models of sexual selection, and our results highlight the potential importance of opsin expression variation as a substrate for signal-preference evolution. Finally, these results suggest a potential sensory mechanism that could drive negative frequency-dependent selection via male-male competition and thus maintain variation in male nuptial color.}, } @article {pmid30073069, year = {2018}, author = {Vierus, T and Gehrig, S and Brunnschweiler, JM and Glaus, K and Zimmer, M and Marie, AD and Rico, C}, title = {Discovery of a multispecies shark aggregation and parturition area in the Ba Estuary, Fiji Islands.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7079-7093}, pmid = {30073069}, issn = {2045-7758}, abstract = {Population declines in shark species have been reported on local and global scales, with overfishing, habitat destruction and climate change posing severe threats. The lack of species-specific baseline data on ecology and distribution of many sharks, however, makes conservation measures challenging. Here, we present a fisheries-independent shark survey from the Fiji Islands, where scientific knowledge on locally occurring elasmobranchs is largely still lacking despite the location's role as a shark hotspot in the Pacific. Juvenile shark abundance in the fishing grounds of the Ba Estuary (north-western Viti Levu) was assessed with a gillnet- and longline-based survey from December 2015 to April 2016. A total of 103 juvenile sharks identified as blacktip Carcharhinus limbatus (n = 57), scalloped hammerhead Sphyrna lewini (n = 35), and great hammerhead Sphyrna mokarran (n = 11) sharks were captured, tagged, and released. The condition of umbilical scars (68% open or semihealed), mean sizes of individuals (±SD) (C. limbatus: 66.5 ± 3.8 cm, S. lewini: 51.8 ± 4.8 cm, S. mokarran 77.4 ± 2.8 cm), and the presence of these species over recent years (based on fishermen interviews), suggest that the Ba Estuary area is a critical habitat for multiple species that are classified as "Near Threatened" or "Endangered." Specifically, the area likely acts as a parturition ground over the studied period, and potentially as a subsequent nursery area. We identified subareas of high abundance and found that temperature, salinity and depth acted as small-scale environmental drivers of shark abundance. The data suggests a tendency for species-specific spatial use, both horizontally (i.e., between sampling areas) and vertically (i.e., across the water column). These results enhance the understanding of shark ecology in Fiji and provide a scientific basis for the implementation of local conservation strategies that contribute to the protection of these threatened species.}, } @article {pmid30073068, year = {2018}, author = {Peng, Y and Fan, M and Wang, Q and Lan, W and Long, Y}, title = {Best hyperspectral indices for assessing leaf chlorophyll content in a degraded temperate vegetation.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7068-7078}, pmid = {30073068}, issn = {2045-7758}, abstract = {Extensive studies have focused on assessing leaf chlorophyll content through spectral indices; however, the accuracy is weakened by limited wavebands and coarse resolution. With hundreds of wavebands, hyperspectral data can substantially capture the essential absorption features of leaf chlorophyll; however, few such studies have been conducted on same species in various degraded vegetations. In this investigation, complete combinations of either original reflectance or first-order derivative spectra we conducted a complete combination on either original reflectance or its first-order derivative value from 350 to 1000 nm to quantify leaf total chlorophyll (Chll), chlorophyll-a (Chla), and chlorophyll-b (Chlb) contents. This was performed using three hyperspectral datasets collected in situ from lightly, moderately, and severely degraded vegetations in temperate Helin County, China. Suitable combinations were selected by comparing the numbers of significant correlation coefficients with leaf Chll, Chla, and Chlb contents. The combinations of reflectance difference (Dij), normalized differences (ND), first-order derivative (FD), and first-order derivative difference (FD(D)) were found to be the most effective. These sensitive band-based combinations were further optimized by means of a stepwise linear regression analysis and were compared with 43 empirical spectral indices, frequently used in the literature. These sensitive band-based combinations on hyperspectral data proved to be the most effective indices for quantifying leaf chlorophyll content (R2 > 0.7, p < 0.01), demonstrating great potential for the use of hyperspectral data in monitoring degraded vegetation at a fine scale.}, } @article {pmid30073067, year = {2018}, author = {Salmon, Y and Li, X and Yang, B and Ma, K and Siegwolf, RTW and Schmid, B}, title = {Surrounding species diversity improves subtropical seedlings' carbon dynamics.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7055-7067}, pmid = {30073067}, issn = {2045-7758}, abstract = {Increasing biodiversity has been linked to higher primary productivity in terrestrial ecosystems. However, the underlying ecophysiological mechanisms remain poorly understood. We investigated the effects of surrounding species richness (monoculture, two- and four-species mixtures) on the ecophysiology of Lithocarpus glaber seedlings in experimental plots in subtropical China. A natural rain event isotopically labelled both the water uptaken by the L. glaber seedlings and the carbon in new photoassimilates through changes of photosynthetic discrimination. We followed the labelled carbon (C) and oxygen (O) in the plant-soil-atmosphere continuum. We measured gas-exchange variables (C assimilation, transpiration and above- and belowground respiration) and δ13C in leaf biomass, phloem, soil microbial biomass, leaf- and soil-respired CO 2 as well as δ18O in leaf and xylem water. The 13C signal in phloem and respired CO 2 in L. glaber in monoculture lagged behind those in species mixture, showing a slower transport of new photoassimilates to and through the phloem in monoculture. Furthermore, leaf-water 18O enrichment above the xylem water in L. glaber increased after the rain in lower diversity plots suggesting a lower ability to compensate for increased transpiration. Lithocarpus glaber in monoculture showed higher C assimilation rate and water-use efficiency. However, these increased C resources did not translate in higher growth of L. glaber in monoculture suggesting the existence of larger nongrowth-related C sinks in monoculture. These ecophysiological responses of L. glaber, in agreement with current understanding of phloem transport are consistent with a stronger competition for water resources in monoculture than in species mixtures. Therefore, increasing species diversity in the close vicinity of the studied plants appears to alleviate physiological stress induced by water competition and to counterbalance the negative effects of interspecific competition on assimilation rates for L. glaber by allowing a higher fraction of the C assimilated to be allocated to growth in species mixture than in monoculture.}, } @article {pmid30073066, year = {2018}, author = {Godó, L and Tóthmérész, B and Valkó, O and Tóth, K and Kiss, R and Radócz, S and Kelemen, A and Török, P and Švamberková, E and Deák, B}, title = {Ecosystem engineering by foxes is mediated by the landscape context-A case study from steppic burial mounds.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7044-7054}, pmid = {30073066}, issn = {2045-7758}, abstract = {In intensively used landscapes, remnant grassland fragments are often restricted to places unsuitable for agricultural cultivation. Such refuges are the ancient burial mounds called "kurgans," which are typical landscape elements of the Eurasian steppe and forest steppe zone. Due to their hill-like shape, loose soil structure and undisturbed status kurgans provide proper habitats for burrowing mammals. Accordingly, grassland vegetation on kurgans is often exposed to bioturbation, which can influence the habitat structure and plant species pool. In our study, we explored the effect of fox burrows and landscape context on the habitat properties and vegetation composition of small landscape elements, using kurgans as model habitats. We surveyed the vegetation of fox burrows and that of the surrounding grassland on five kurgans situated in cleared landscapes surrounded by arable lands and five kurgans in complex landscapes surrounded by grazed grasslands. We recorded the percentage cover of vascular plants, the amount of litter, and soil moisture content in twelve 0.5 m × 0.5 m plots per kurgan, in a total of 120 plots. We found that foxes considerably transformed habitat conditions and created microhabitats by changing the soil nutrient availability and reducing total vegetation cover and litter. Several grassland specialist species, mostly grasses (Agropyron cristatum, Elymus hispidus, and Stipa capillata) established in the newly created microhabitats, although the cover of noxious species was also considerable. We found that landscape context influenced the sort of species which could establish on kurgans by affecting the available species pool and soil moisture. Our results revealed that foxes act as ecosystem engineers on kurgans by transforming abiotic and biotic conditions by burrowing. Their engineering activity maintains disturbance-dependent components of dry grasslands and increases local environmental heterogeneity.}, } @article {pmid30073065, year = {2018}, author = {Griffiths, CA and Patterson, TA and Blanchard, JL and Righton, DA and Wright, SR and Pitchford, JW and Blackwell, PG}, title = {Scaling marine fish movement behavior from individuals to populations.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7031-7043}, pmid = {30073065}, issn = {2045-7758}, abstract = {Understanding how, where, and when animals move is a central problem in marine ecology and conservation. Key to improving our knowledge about what drives animal movement is the rising deployment of telemetry devices on a range of free-roaming species. An increasingly popular way of gaining meaningful inference from an animal's recorded movements is the application of hidden Markov models (HMMs), which allow for the identification of latent behavioral states in the movement paths of individuals. However, the use of HMMs to explore the population-level consequences of movement is often limited by model complexity and insufficient sample sizes. Here, we introduce an alternative approach to current practices and provide evidence of how the inclusion of prior information in model structure can simplify the application of HMMs to multiple animal movement paths with two clear benefits: (a) consistent state allocation and (b) increases in effective sample size. To demonstrate the utility of our approach, we apply HMMs and adapted HMMs to over 100 multivariate movement paths consisting of conditionally dependent daily horizontal and vertical movements in two species of demersal fish: Atlantic cod (Gadus morhua; n = 46) and European plaice (Pleuronectes platessa; n = 61). We identify latent states corresponding to two main underlying behaviors: resident and migrating. As our analysis considers a relatively large sample size and states are allocated consistently, we use collective model output to investigate state-dependent spatiotemporal trends at the individual and population levels. In particular, we show how both species shift their movement behaviors on a seasonal basis and demonstrate population space use patterns that are consistent with previous individual-level studies. Tagging studies are increasingly being used to inform stock assessment models, spatial management strategies, and monitoring of marine fish populations. Our approach provides a promising way of adding value to tagging studies because inferences about movement behavior can be gained from a larger proportion of datasets, making tagging studies more relevant to management and more cost-effective.}, } @article {pmid30073064, year = {2018}, author = {Strani, F and Profico, A and Manzi, G and Pushkina, D and Raia, P and Sardella, R and DeMiguel, D}, title = {MicroWeaR: A new R package for dental microwear analysis.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7022-7030}, pmid = {30073064}, issn = {2045-7758}, abstract = {Mastication of dietary items with different mechanical properties leaves distinctive microscopic marks on the surface of tooth enamel. The inspection of such marks (dental microwear analysis) is informative about the dietary habitus in fossil as well as in modern species. Dental microwear analysis relies on the morphology, abundance, direction, and distribution of these microscopic marks. We present a new freely available software implementation, MicroWeaR, that, compared to traditional dental microwear tools, allows more rapid, observer error free, and inexpensive quantification and classification of all the microscopic marks (also including for the first time different subtypes of scars). Classification parameters and graphical rendering of the output are fully settable by the user. MicroWeaR includes functions to (a) sample the marks, (b) classify features into categories as pits or scratches and then into their respective subcategories (large pits, coarse scratches, etc.), (c) generate an output table with summary information, and (d) obtain a visual surface-map where marks are highlighted. We provide a tutorial to reproduce the steps required to perform microwear analysis and to test tool functionalities. Then, we present two case studies to illustrate how MicroWeaR works. The first regards a Miocene great ape obtained from through environmental scanning electron microscope, and other a Pleistocene cervid acquired by a stereomicroscope.}, } @article {pmid30073063, year = {2018}, author = {Cavieres, G and Bogdanovich, JM and Toledo, P and Bozinovic, F}, title = {Fluctuating thermal environments and time-dependent effects on fruit fly egg-hatching performance.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7014-7021}, pmid = {30073063}, issn = {2045-7758}, abstract = {Organismal performance in a changing environment is dependent on temporal patterns and duration of exposure to thermal variability. We experimentally assessed the time-dependent effects of thermal variability (i.e., patterns of thermal exposure) on the hatching performance of Drosophila melanogaster. Flies were collected in central Chile and maintained for four generations in laboratory conditions. Fourth generation eggs were acclimated to different thermal fluctuation cycles until hatching occurred. Our results show that the frequency of extreme thermal events has a significant effect on hatching success. Eggs exposed to 24 hr cycles of thermal fluctuation had a higher proportion of eggs that hatched than those acclimated to shorter (6 and 12 hr) and longer cycles (48 hr). Furthermore, eggs subjected to frequent thermal fluctuations hatched earlier than those acclimated to less frequent thermal fluctuations. Overall, we show that, egg-to-adult viability is dependent on the pattern of thermal fluctuations experienced during ontogeny; thus, the pattern of thermal fluctuation experienced by flies has a significant and until now unappreciated impact on fitness.}, } @article {pmid30073062, year = {2018}, author = {Nadukkalam Ravindran, P and Bentzen, P and Bradbury, IR and Beiko, RG}, title = {PMERGE: Computational filtering of paralogous sequences from RAD-seq data.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {7002-7013}, pmid = {30073062}, issn = {2045-7758}, abstract = {Restriction-site associated DNA sequencing (RAD-seq) can identify and score thousands of genetic markers from a group of samples for population-genetics studies. One challenge of de novo RAD-seq analysis is to distinguish paralogous sequence variants (PSVs) from true single-nucleotide polymorphisms (SNPs) associated with orthologous loci. In the absence of a reference genome, it is difficult to differentiate true SNPs from PSVs, and their impact on downstream analysis remains unclear. Here, we introduce a network-based approach, PMERGE that connects fragments based on their DNA sequence similarity to identify probable PSVs. Applying our method to de novo RAD-seq data from 150 Atlantic salmon (Salmo salar) samples collected from 15 locations across the Southern Newfoundland coast allowed the identification of 87% of total PSVs identified through alignment to the Atlantic salmon genome. Removal of these paralogs altered the inferred population structure, highlighting the potential impact of filtering in RAD-seq analysis. PMERGE is also applied to a green crab (Carcinus maenas) data set consisting of 242 samples from 11 different locations and was successfully able to identify and remove the majority of paralogous loci (62%). The PMERGE software can be run as part of the widely used Stacks analysis package.}, } @article {pmid30073061, year = {2018}, author = {Del Castillo, RF and Trujillo-Argueta, S}, title = {On the possible role of nonreproductive traits for the evolution of unisexuality: Life-history variation among males, females, and hermaphrodites in Opuntia robusta (Cactaceae).}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6988-7001}, pmid = {30073061}, issn = {2045-7758}, abstract = {In angiosperms, dioecy has arisen in 871-5,000 independent events, distributed in approximately 43% of the flowering families. The reproductive superiority of unisexuals has been the favorite explanation for the evolution of separate sexes. However, in several instances, the observed reproductive performance of unisexuals, if any, does not seem to compensate for the loss of one of the sex functions. The involvement of fitness components not directly associated with reproduction is a plausible hypothesis that has received little attention. Life-history traits recently recognized as predictors of plant performance were compared among males, females, and hermaphrodites of a rare trioecious Opuntia robusta population in the field, using the cladode as the study unit. Cladode mortality by domestic herbivores was common and higher in females and hermaphrodites than in males. Males, females, or both displayed lower shrinkage and higher rates of survival, growth, and reproductive frequency than hermaphrodites. Unisexuals simultaneously outperformed hermaphrodites in demographic traits known to compete for common limiting resources, such as the acceleration of reproductive maturation (progenesis) and survival. A meta-analysis combining the outcomes of each of the analyzed life-history traits revealed a tendency of males (d++ = 1.03) and females (d++ = 0.93) to outperform hermaphrodites in presumably costly demographic options. Clonality is induced by human or domestic animal plant sectioning; and males and females highly exceeded hermaphrodites in their clonality potential by a factor of 8.3 and 5.3, respectively. The performances of unisexuals in the analyzed life-history traits may enhance their reproductive potential in the long run and their clonality potential and could explain the observed increase of unisexuality in the population. Life-history traits can be crucial for the evolution of unisexuality, but their impact appears to be habitat specific and may involve broad ontogenetic changes.}, } @article {pmid30073060, year = {2018}, author = {Jiang, L and You, Z and Yu, P and Ruan, Q and Chen, W}, title = {The first complete mitochondrial genome sequence of Nanorana parkeri and Nanorana ventripunctata (Amphibia: Anura: Dicroglossidae), with related phylogenetic analyses.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6972-6987}, pmid = {30073060}, issn = {2045-7758}, abstract = {Members of the Nanorana genus (family Dicroglossidae) are often referred to as excellent model species with which to study amphibian adaptations to extreme environments and also as excellent keystone taxa for providing insights into the evolution of the Dicroglossidae. However, a complete mitochondrial genome is currently only available for Nanorana pleskei. Thus, we analyzed the complete mitochondrial genomes of Nanorana parkeri and Nanorana ventripunctata to investigate their evolutionary relationships within Nanorana and their phylogenetic position in the family Dicroglossidae. Our results showed that the genomes of N. parkeri (17,837 bp) and N. ventripunctata (18,373 bp) encode 13 protein-coding genes (PCGs), two ribosomal RNA genes, 23 transfer RNA (tRNA) genes, and a noncoding control region. Overall sequences and genome structure of the two species showed high degree of similarity with N. pleskei, although the motif structures and repeat sequences of the putative control region showed clear differences among these three Nanorana species. In addition, a tandem repeat of the tRNA-Met gene was found located between the tRNA-Gln and ND2 genes. On both the 5' and 3'-sides, the control region possessed distinct repeat regions; however, the CSB-2 motif was not found in N. pleskei. Based on the nucleotide sequences of 13 PCGs, our phylogenetic analyses, using Bayesian inference and maximum-likelihood methods, illustrate the taxonomic status of Nanorana with robust support showing that N. ventripunctata and N. pleskei are more closely related than they are to N. parkeri. In conclusion, our analyses provide a more robust and reliable perspective on the evolutionary history of Dicroglossidae than earlier analyses, which used only a single species (N. pleskei).}, } @article {pmid30073059, year = {2018}, author = {Pereira, AG and Schrago, CG}, title = {Incomplete lineage sorting impacts the inference of macroevolutionary regimes from molecular phylogenies when concatenation is employed: An analysis based on Cetacea.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6965-6971}, pmid = {30073059}, issn = {2045-7758}, abstract = {Interest in methods that estimate speciation and extinction rates from molecular phylogenies has increased over the last decade. The application of such methods requires reliable estimates of tree topology and node ages, which are frequently obtained using standard phylogenetic inference combining concatenated loci and molecular dating. However, this practice disregards population-level processes that generate gene tree/species tree discordance. We evaluated the impact of employing concatenation and coalescent-based phylogeny inference in recovering the correct macroevolutionary regime using simulated data based on the well-established diversification rate shift of delphinids in Cetacea. We found that under scenarios of strong incomplete lineage sorting, macroevolutionary analysis of phylogenies inferred by concatenating loci failed to recover the delphinid diversification shift, while the coalescent-based tree consistently retrieved the correct rate regime. We suggest that ignoring microevolutionary processes reduces the power of methods that estimate macroevolutionary regimes from molecular data.}, } @article {pmid30073058, year = {2018}, author = {Marques, RV and Sarmento, RA and Oliveira, AG and Rodrigues, DM and Venzon, M and Pedro-Neto, M and Pallini, A and Janssen, A}, title = {Reciprocal intraguild predation and predator coexistence.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6952-6964}, pmid = {30073058}, issn = {2045-7758}, abstract = {Intraguild predation is a mix of competition and predation and occurs when one species feeds on another species that uses similar resources. Theory predicts that intraguild predation hampers coexistence of species involved, but it is common in nature. It has been suggested that increasing habitat complexity and the presence of alternative food may promote coexistence. Reciprocal intraguild predation limits possibilities for coexistence even further. Habitat complexity and the presence of alternative food are believed to promote coexistence. We investigated this using two species of predatory mites, Iphiseiodes zuluagai and Euseius concordis, by assessing co-occurrence in the field and on arenas differing in spatial structure in the laboratory. The predators co-occured on the same plants in the field. In the laboratory, adults of the two mites fed on juveniles of the other species, both in the presence and the absence of a shared food source, showing that the two species are involved in reciprocal intraguild predation. Adults of I. zuluagai also attacked adults of E. concordis. This suggests limited possibilities for coexistence of the two species. Indeed, E. concordis invariably went extinct extremely rapidly on arenas without spatial structure with populations consisting of all stages of the two predators and with a shared resource. Coexistence was prolonged on host plant leaves with extra food sources, but E. concordis still went extinct. On small, intact plants, coexistence of the two species was much longer, and ended with the other species, I. zuluagai, often going extinct. These results suggest that spatial structure and the presence of alternative food increase the coexistence period of intraguild predators.}, } @article {pmid30073057, year = {2018}, author = {Iyiola, OA and Nneji, LM and Mustapha, MK and Nzeh, CG and Oladipo, SO and Nneji, IC and Okeyoyin, AO and Nwani, CD and Ugwumba, OA and Ugwumba, AAA and Faturoti, EO and Wang, YY and Chen, J and Wang, WZ and Adeola, AC}, title = {DNA barcoding of economically important freshwater fish species from north-central Nigeria uncovers cryptic diversity.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6932-6951}, pmid = {30073057}, issn = {2045-7758}, abstract = {This study examines the utility of morphology and DNA barcoding in species identification of freshwater fishes from north-central Nigeria. We compared molecular data (mitochondrial cytochrome c oxidase subunit I (COI) sequences) of 136 de novo samples from 53 morphologically identified species alongside others in GenBank and BOLD databases. Using DNA sequence similarity-based (≥97% cutoff) identification technique, 50 (94.30%) and 24 (45.30%) species were identified to species level using GenBank and BOLD databases, respectively. Furthermore, we identified cases of taxonomic problems in 26 (49.00%) morphologically identified species. There were also four (7.10%) cases of mismatch in DNA barcoding in which our query sequence in GenBank and BOLD showed a sequence match with different species names. Using DNA barcode reference data, we also identified four unknown fish samples collected from fishermen to species level. Our Neighbor-joining (NJ) tree analysis recovers several intraspecific species clusters with strong bootstrap support (≥95%). Analysis uncovers two well-supported lineages within Schilbe intermedius. The Bayesian phylogenetic analyses of Nigerian S. intermedius with others from GenBank recover four lineages. Evidence of genetic structuring is consistent with geographic regions of sub-Saharan Africa. Thus, cryptic lineage diversity may illustrate species' adaptive responses to local environmental conditions. Finally, our study underscores the importance of incorporating morphology and DNA barcoding in species identification. Although developing a complete DNA barcode reference library for Nigerian ichthyofauna will facilitate species identification and diversity studies, taxonomic revisions of DNA sequences submitted in databases alongside voucher specimens are necessary for a reliable taxonomic and diversity inventory.}, } @article {pmid30073056, year = {2018}, author = {Coleman, JM and Benowitz, KM and Jost, AG and Matzkin, LM}, title = {Behavioral evolution accompanying host shifts in cactophilic Drosophila larvae.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6921-6931}, pmid = {30073056}, issn = {2045-7758}, abstract = {For plant utilizing insects, the shift to a novel host is generally accompanied by a complex set of phenotypic adaptations. Many such adaptations arise in response to differences in plant chemistry, competitive environment, or abiotic conditions. One less well-understood factor in the evolution of phytophagous insects is the selective environment provided by plant shape and volume. Does the physical structure of a new plant host favor certain phenotypes? Here, we use cactophilic Drosophila, which have colonized the necrotic tissues of cacti with dramatically different shapes and volumes, to examine this question. Specifically, we analyzed two behavioral traits in larvae, pupation height, and activity that we predicted might be related to the ability to utilize variably shaped hosts. We found that populations of D. mojavensis living on lengthy columnar or barrel cactus hosts have greater activity and pupate higher in a laboratory environment than populations living on small and flat prickly pear cactus cladodes. Crosses between the most phenotypically extreme populations suggest that the genetic architectures of these behaviors are distinct. A comparison of activity in additional cactophilic species that are specialized on small and large cactus hosts shows a consistent trend. Thus, we suggest that greater motility and an associated tendency to pupate higher in the laboratory are potential larval adaptations for life on a large plant where space is more abundant and resources may be more sparsely distributed.}, } @article {pmid30073055, year = {2018}, author = {Lee, MB and Carroll, JP}, title = {Effects of patch size and basal area on avian taxonomic and functional diversity in pine forests: Implication for the influence of habitat quality on the species-area relationship.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6909-6920}, pmid = {30073055}, issn = {2045-7758}, abstract = {Relationships between avian diversity and habitat area are assumed to be positive; however, often little attention has given to how these relationships can be influenced by the habitat structure or quality. In addition, other components of biodiversity, such as functional diversity, are often overlooked in assessing habitat patch value. In the Sandhills Ecoregion of Georgia, USA, we investigated the relationship between avian species richness and functional diversity, forest basal area, and patch size in pine forests using basal area as a surrogate for overstory structure which in turn impacts vegetation structure and determines habitat quality within a patch. We conducted bird surveys in planted mature pine stands, during breeding season of 2011. We used three classes of stand basal area (BA): OS, overstocked (BA ≥ 23 m2/ha); FS, fully/densely stocked (13.8 m2/ha ≤ BA < 23 m2/ha); and MS, moderately stocked (2.3 m2/ha ≤ BA < 13.8 m2/ha). MS patches showed more structural diversity due to higher herbaceous vegetation cover than other two pine stocking classes of patches. Total species richness and functional richness increased with the size of MS patches, whereas functional divergence decreased with the size of OS patches (p < 0.05). Functional richness tended to be lower than expected as the size of OS patches increased. Greater richness of pine-grassland species was also found at MS patches. Percent cover of MS patches within a landscape influenced positively the richness of pine-grassland species (p < 0.05). Our results suggest that (a) avian species-habitat area relationship can be affected by habitat quality (structural diversity) and varies depending on diversity indices considered, and (b) it is important to maintain moderate or low levels of pine basal area and to preserve large-sized patches of the level of basal area to enhance both taxonomic and functional diversity in managed pine forests.}, } @article {pmid30073054, year = {2018}, author = {Briedis, M and Hahn, S and Krist, M and Adamík, P}, title = {Finish with a sprint: Evidence for time-selected last leg of migration in a long-distance migratory songbird.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6899-6908}, pmid = {30073054}, issn = {2045-7758}, abstract = {Under time-selected migration, birds should choose a strategy for outcompeting rivals over securing access to prime resources at the final destination. Thus, migration can be viewed as a race among individuals where winners are arriving first when conditions are suitable. The sprint migration hypothesis predicts that individuals shift from maximum sustained speed to a final burst of sprint to shorten the transition from migration to breeding (Alerstam, 2006). In this study, we test the hypothesis of a final sprint migration in a long-distance Afro-Palearctic migrant, the collared flycatcher Ficedula albicollis, during autumn and spring, and compare migration strategies between the seasons. In both seasons, collared flycatchers evidently exhibited sprint migration by increasing their overall speed over the last leg of migration after the Sahara crossing. This phenomenon was more pronounced in spring, contributing to overall faster spring migration and possibly highlighting higher importance for early arrival at the breeding grounds. In both seasons and particularly in spring, late departing individuals flew at a faster rate, partially being able to catch up with their early departing conspecifics. Differential fueling strategies may play an important role in determining migration speed, especially during the early stages of the migration, and might explain the observed differences in migration speeds between late and early departing individuals. Our findings suggest competition for early arrival at the breeding and at the nonbreeding destinations alike. Sprint migration might be an appropriate strategy to gain advantage over conspecifics and settle in prime territories as well as to cope with the increasingly earlier springs at high latitudes.}, } @article {pmid30073053, year = {2018}, author = {Müller, T and Lamprecht, TD and Schrieber, K}, title = {Lifetime inbreeding depression in a leaf beetle.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6889-6898}, pmid = {30073053}, issn = {2045-7758}, abstract = {Ongoing habitat loss and fragmentation result in rapid population size reductions, which can increase the levels of inbreeding. Consequently, many species are threatened by inbreeding depression, a loss of individual fitness following the mating of close relatives. Here, we investigated inbreeding effects on fitness-related traits throughout the lifetime of the mustard leaf beetle (Phaedon cochleariae) and mechanisms for the avoidance of inbreeding. Previously, we found that these beetles have family-specific cuticular hydrocarbon profiles, which are likely not used as recognition cue for precopulatory inbreeding avoidance. Thus, we examined whether adult beetles show postcopulatory inbreeding avoidance instead. For this purpose, we determined the larval hatching rate of eggs laid by females mated sequentially with two nonsiblings, two siblings, a nonsibling, and a sibling or vice versa. The beetles suffered from inbreeding depression throughout their entire ontogeny, as evinced by a prolonged larval development, a decreased larval and adult survival and a decreased reproductive output of inbred compared to outbred individuals. The highest larval hatching rates were detected when females were mated with two nonsiblings or first with a sibling and second with a nonsibling. Significantly lower hatching rates were measured in the treatments with a sibling as second male. Thus, the results do not support the existence of postcopulatory inbreeding avoidance in P. cochleariae, but revealed evidence for second male sperm precedence. Consequently, an alternative strategy to avoid inbreeding costs might exist in this beetle, such as a polyandrous mating system, potentially coupled with a specific dispersal behavior.}, } @article {pmid30073052, year = {2018}, author = {Bhattacharya, A and Pak, HT and Bashey, F}, title = {Plastic responses to competition: Does bacteriocin production increase in the presence of nonself competitors?.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6880-6888}, pmid = {30073052}, issn = {2045-7758}, abstract = {Anticompetitor traits such as the production of allelopathic toxins can confer significant competitive benefits but are often costly to produce. Evolution of these traits may be facilitated by environment-specific induction; however, the extent to which costly anticompetitor traits are induced by competitors is not well explored. Here, we addressed this question using bacteriocins, which are highly specific, proteinaceous anticompetitor toxins, produced by most lineages of bacteria and archaea. We tested the prediction that bacteriocin production is phenotypically plastic and induced by the presence of competitors by examining bacteriocin production in the presence and absence of nonself competitors over the course of growth of a producing strain. Our results show that bacteriocin production is detectable only at high cell densities, when competition for resources is high. However, the amount of bacteriocin activity was not significantly different in the presence vs. the absence of nonself competitors. These results suggest that bacteriocin production is either (a) canalized, constitutively produced by a fixed frequency of cells in the population or (b) induced by generic cues of competition, rather than specific self/nonself discrimination. Such a nonspecific response to competition could be favored in the natural environment where competition is ubiquitous.}, } @article {pmid30073051, year = {2018}, author = {Gao, J and Liu, Y}, title = {Climate stability is more important than water-energy variables in shaping the elevational variation in species richness.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6872-6879}, pmid = {30073051}, issn = {2045-7758}, abstract = {Changes in climate variables have an important impact on the prediction and protection of elevational biodiversity. Gaps exist in our understanding of the elevational distribution patterns in seed plant species richness. Our study examines the importance of climate variables in shaping the elevational variation in species richness. The importance of boundary constraint was also taken into account. Model selection based on Akaike's information criterion was used to select the best explaining climate models. Variation partitioning was used to assess the independent and joint effects of water-energy, physiological tolerance, and environmental stability variables on species richness. Our results revealed that: (a) Both raw (boundary constraint unreduced) and estimated (boundary constraint reduced) species richness showed large elevational variation, with the peak species richness seen at midelevations. The environmental variables were better at explaining the distribution pattern of species richness along the elevation, when the effect of boundary constraint was reduced; (b) the physiological tolerance and environmental stability variables explained more variation in raw and estimated species richness compared with the water-energy variables. Estimated species richness was better explained (98.6%) by the environmental variables than raw species richness (94%); (c) the water-related variables generally had the highest independent effect on raw and estimated species richness and were dominant in shaping the elevational variation in species richness. Our findings quantify the influence of boundary constraint on the distribution pattern of species along an altitudinal gradient and compare the relative contributions of environmental stability and water-energy in explaining the altitude gradient distribution pattern of plant seed species.}, } @article {pmid30073050, year = {2018}, author = {Berriozabal-Islas, C and Rodrigues, JFM and Ramírez-Bautista, A and Becerra-López, JL and Nieto-Montes de Oca, A}, title = {Effect of climate change in lizards of the genus Xenosaurus (Xenosauridae) based on projected changes in climatic suitability and climatic niche conservatism.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6860-6871}, pmid = {30073050}, issn = {2045-7758}, abstract = {Accelerated climate change represents a major threat to the health of the planet's biodiversity. Particularly, lizards of the genus Xenosaurus might be negatively affected by this phenomenon because several of its species have restricted distributions, low vagility, and preference for low temperatures. No study, however, has examined the climatic niche of the species of this genus and how their distribution might be influenced by different climate change scenarios. In this project, we used a maximum entropy approach to model the climatic niche of 10 species of the genus Xenosaurus under present and future suitable habitat, considering a climatic niche conservatism context. Therefore, we performed a similarity analysis of the climatic niche between each species of the genus Xenosaurus. Our results suggest that a substantial decrease in suitable habitat for all species will occur by 2070. Among the most affected species, X. tzacualtipantecus will not have suitable conditions according to its climatic niche requirements and X. phalaroanthereon will lose 85.75% of its current suitable area. On the other hand, we found low values of conservatism of the climatic niche among species. Given the limited capacity of dispersion and the habitat specificity of these lizards, it seems unlikely that fast changes would occur in the distribution of these species facing climate change. The low conservatism in climatic niche we found in Xenosaurus suggests that these species might have the capacity to adapt to the new environmental conditions originated by climate change.}, } @article {pmid30073049, year = {2018}, author = {Cenci, S and Song, C and Saavedra, S}, title = {Rethinking the importance of the structure of ecological networks under an environment-dependent framework.}, journal = {Ecology and evolution}, volume = {8}, number = {14}, pages = {6852-6859}, pmid = {30073049}, issn = {2045-7758}, abstract = {A major quest in network and community ecology has been centered on understanding the importance of structural patterns in species interaction networks-the synthesis of who interacts with whom in a given location and time. In the past decades, much effort has been devoted to infer the importance of a particular structure by its capacity to tolerate an external perturbation on its structure or dynamics. Here, we demonstrate that such a perspective leads to inconsistent conclusions. That is, the importance of a network structure changes as a function of the external perturbations acting on a community at any given point in time. Thus, we discuss a research agenda to investigate the relative importance of the structure of ecological networks under an environment-dependent framework. We hypothesize that only by studying systematically the link between network structure and community dynamics under an environment-dependent framework, we can uncover the limits at which communities can tolerate environmental changes.}, } @article {pmid30072712, year = {2018}, author = {Du Toit, A}, title = {Teamwork pays off.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {521}, doi = {10.1038/s41579-018-0068-2}, pmid = {30072712}, issn = {1740-1534}, } @article {pmid30072577, year = {2018}, author = {Knouse, KW and deGruyter, JN and Schmidt, MA and Zheng, B and Vantourout, JC and Kingston, C and Mercer, SE and Mcdonald, IM and Olson, RE and Zhu, Y and Hang, C and Zhu, J and Yuan, C and Wang, Q and Park, P and Eastgate, MD and Baran, PS}, title = {Unlocking P(V): Reagents for chiral phosphorothioate synthesis.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6408}, pages = {1234-1238}, doi = {10.1126/science.aau3369}, pmid = {30072577}, issn = {1095-9203}, support = {R35 GM118176/GM/NIGMS NIH HHS/United States ; }, mesh = {Genetic Therapy ; Isomerism ; Nucleotides/*chemistry ; Phosphorothioate Oligonucleotides/*chemical synthesis/chemistry/therapeutic use ; Sulfur/chemistry ; }, abstract = {Phosphorothioate nucleotides have emerged as powerful pharmacological substitutes of their native phosphodiester analogs with important translational applications in antisense oligonucleotide (ASO) therapeutics and cyclic dinucleotide (CDN) synthesis. Stereocontrolled installation of this chiral motif has long been hampered by the systemic use of phosphorus(III) [P(III)]-based reagent systems as the sole practical means of oligonucleotide assembly. A fundamentally different approach is described herein: the invention of a P(V)-based reagent platform for programmable, traceless, diastereoselective phosphorus-sulfur incorporation. The power of this reagent system is demonstrated through the robust and stereocontrolled synthesis of various nucleotidic architectures, including ASOs and CDNs, via an efficient, inexpensive, and operationally simple protocol.}, } @article {pmid30072576, year = {2018}, author = {Emilsson, V and Ilkov, M and Lamb, JR and Finkel, N and Gudmundsson, EF and Pitts, R and Hoover, H and Gudmundsdottir, V and Horman, SR and Aspelund, T and Shu, L and Trifonov, V and Sigurdsson, S and Manolescu, A and Zhu, J and Olafsson, Ö and Jakobsdottir, J and Lesley, SA and To, J and Zhang, J and Harris, TB and Launer, LJ and Zhang, B and Eiriksdottir, G and Yang, X and Orth, AP and Jennings, LL and Gudnason, V}, title = {Co-regulatory networks of human serum proteins link genetics to disease.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {769-773}, pmid = {30072576}, issn = {1095-9203}, support = {N01AG12100/AG/NIA NIH HHS/United States ; Z01 AG007380-02/NULL/Intramural NIH HHS/United States ; HHSN271201200022C/AG/NIA NIH HHS/United States ; R01 DK104363/DK/NIDDK NIH HHS/United States ; Z99 AG999999/NULL/Intramural NIH HHS/United States ; }, mesh = {Aptamers, Nucleotide ; Blood Proteins/*analysis/*genetics ; Cardiovascular Diseases/*genetics ; Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Iceland ; Metabolic Diseases/*genetics ; Metabolic Networks and Pathways ; Proteome/*analysis/*genetics ; Proteomics/*methods ; }, abstract = {Proteins circulating in the blood are critical for age-related disease processes; however, the serum proteome has remained largely unexplored. To this end, 4137 proteins covering most predicted extracellular proteins were measured in the serum of 5457 Icelanders over 65 years of age. Pairwise correlation between proteins as they varied across individuals revealed 27 different network modules of serum proteins, many of which were associated with cardiovascular and metabolic disease states, as well as overall survival. The protein modules were controlled by cis- and trans-acting genetic variants, which in many cases were also associated with complex disease. This revealed co-regulated groups of circulating proteins that incorporated regulatory control between tissues and demonstrated close relationships to past, current, and future disease states.}, } @article {pmid30072540, year = {2018}, author = {Abderrahman, B}, title = {Paying it forward as a mentor.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {522}, doi = {10.1126/science.361.6401.522}, pmid = {30072540}, issn = {1095-9203}, } @article {pmid30072539, year = {2018}, author = {Tucci, S and Vohr, SH and McCoy, RC and Vernot, B and Robinson, MR and Barbieri, C and Nelson, BJ and Fu, W and Purnomo, GA and Sudoyo, H and Eichler, EE and Barbujani, G and Visscher, PM and Akey, JM and Green, RE}, title = {Evolutionary history and adaptation of a human pygmy population of Flores Island, Indonesia.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {511-516}, doi = {10.1126/science.aar8486}, pmid = {30072539}, issn = {1095-9203}, support = {R01 GM110068/GM/NIGMS NIH HHS/United States ; //European Research Council/International ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adaptation, Biological/*genetics ; Animals ; *Biological Evolution ; Body Height/*genetics ; Dwarfism/*genetics ; Gene Flow ; Genome, Human ; Humans ; Indonesia ; *Islands ; Neanderthals/genetics ; Population/*genetics ; *Selection, Genetic ; }, abstract = {Flores Island, Indonesia, was inhabited by the small-bodied hominin species Homo floresiensis, which has an unknown evolutionary relationship to modern humans. This island is also home to an extant human pygmy population. Here we describe genome-scale single-nucleotide polymorphism data and whole-genome sequences from a contemporary human pygmy population living on Flores near the cave where H. floresiensis was found. The genomes of Flores pygmies reveal a complex history of admixture with Denisovans and Neanderthals but no evidence for gene flow with other archaic hominins. Modern individuals bear the signatures of recent positive selection encompassing the FADS (fatty acid desaturase) gene cluster, likely related to diet, and polygenic selection acting on standing variation that contributed to their short-stature phenotype. Thus, multiple independent instances of hominin insular dwarfism occurred on Flores.}, } @article {pmid30072538, year = {2018}, author = {Zhou, Y and Yan, A and Han, H and Li, T and Geng, Y and Liu, X and Meyerowitz, EM}, title = {HAIRY MERISTEM with WUSCHEL confines CLAVATA3 expression to the outer apical meristem layers.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {502-506}, pmid = {30072538}, issn = {1095-9203}, support = {R01 GM104244/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/cytology/*genetics/metabolism ; Arabidopsis Proteins/*genetics/*metabolism ; Cell Polarity ; *Gene Expression Regulation, Plant ; Histone Acetyltransferases/genetics/*metabolism ; Homeodomain Proteins/*genetics ; Meristem/*cytology/metabolism ; Stem Cell Niche/*genetics ; }, abstract = {The control of the location and activity of stem cells depends on spatial regulation of gene activities in the stem cell niche. Using computational and experimental approaches, we have tested and found support for a hypothesis for gene interactions that specify the Arabidopsis apical stem cell population. The hypothesis explains how the WUSCHEL gene product, synthesized basally in the meristem, induces CLAVATA3-expressing stem cells in the meristem apex but, paradoxically, not in the basal domain where WUSCHEL itself is expressed. The answer involves the activity of the small family of HAIRY MERISTEM genes, which prevent the activation of CLAVATA3 and which are expressed basally in the shoot meristem.}, } @article {pmid30072537, year = {2018}, author = {Evans, NP and Bauska, TK and Gázquez-Sánchez, F and Brenner, M and Curtis, JH and Hodell, DA}, title = {Quantification of drought during the collapse of the classic Maya civilization.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {498-501}, doi = {10.1126/science.aas9871}, pmid = {30072537}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Civilization/*history ; Droughts/*history ; History, Ancient ; Lakes ; Mexico ; }, abstract = {The demise of Lowland Classic Maya civilization during the Terminal Classic Period (~800 to 1000 CE) is a well-cited example of how past climate may have affected ancient societies. Attempts to estimate the magnitude of hydrologic change, however, have met with equivocal success because of the qualitative and indirect nature of available climate proxy data. We reconstructed the past isotopic composition (δ18O, δD, 17O-excess, and d-excess) of water in Lake Chichancanab, Mexico, using a technique that involves isotopic analysis of the structurally bound water in sedimentary gypsum, which was deposited under drought conditions. The triple oxygen and hydrogen isotope data provide a direct measure of past changes in lake hydrology. We modeled the data and conclude that annual precipitation decreased between 41 and 54% (with intervals of up to 70% rainfall reduction during peak drought conditions) and that relative humidity declined by 2 to 7% compared to present-day conditions.}, } @article {pmid30072536, year = {2018}, author = {Zhang, L and Chen, J and Fan, L and Diéguez, O and Cao, J and Pan, Z and Wang, Y and Wang, J and Kim, M and Deng, S and Wang, J and Wang, H and Deng, J and Yu, R and Scott, JF and Xing, X}, title = {Giant polarization in super-tetragonal thin films through interphase strain.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {494-497}, doi = {10.1126/science.aan2433}, pmid = {30072536}, issn = {1095-9203}, abstract = {Strain engineering has emerged as a powerful tool to enhance the performance of known functional materials. Here we demonstrate a general and practical method to obtain super-tetragonality and giant polarization using interphase strain. We use this method to create an out-of-plane-to-in-plane lattice parameter ratio of 1.238 in epitaxial composite thin films of tetragonal lead titanate (PbTiO3), compared to 1.065 in bulk. These thin films with super-tetragonal structure possess a giant remanent polarization, 236.3 microcoulombs per square centimeter, which is almost twice the value of known ferroelectrics. The super-tetragonal phase is stable up to 725°C, compared to the bulk transition temperature of 490°C. The interphase-strain approach could enhance the physical properties of other functional materials.}, } @article {pmid30072535, year = {2018}, author = {Giraldo-Gallo, P and Galvis, JA and Stegen, Z and Modic, KA and Balakirev, FF and Betts, JB and Lian, X and Moir, C and Riggs, SC and Wu, J and Bollinger, AT and He, X and Božović, I and Ramshaw, BJ and McDonald, RD and Boebinger, GS and Shekhter, A}, title = {Scale-invariant magnetoresistance in a cuprate superconductor.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {479-481}, doi = {10.1126/science.aan3178}, pmid = {30072535}, issn = {1095-9203}, abstract = {The anomalous metallic state in the high-temperature superconducting cuprates is masked by superconductivity near a quantum critical point. Applying high magnetic fields to suppress superconductivity has enabled detailed studies of the normal state, yet the direct effect of strong magnetic fields on the metallic state is poorly understood. We report the high-field magnetoresistance of thin-film La2-x Sr x CuO4 cuprate in the vicinity of the critical doping, 0.161 ≤ p ≤ 0.190. We find that the metallic state exposed by suppressing superconductivity is characterized by magnetoresistance that is linear in magnetic fields up to 80 tesla. The magnitude of the linear-in-field resistivity mirrors the magnitude and doping evolution of the well-known linear-in-temperature resistivity that has been associated with quantum criticality in high-temperature superconductors.}, } @article {pmid30072534, year = {2018}, author = {Troth, A and Puzey, JR and Kim, RS and Willis, JH and Kelly, JK}, title = {Selective trade-offs maintain alleles underpinning complex trait variation in plants.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {475-478}, doi = {10.1126/science.aat5760}, pmid = {30072534}, issn = {1095-9203}, support = {R01 GM073990/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Evolution, Molecular ; Gene Frequency ; Genetic Fitness ; Mimulus/*genetics ; *Multifactorial Inheritance ; Plants/*genetics ; Polymorphism, Genetic ; *Selection, Genetic ; }, abstract = {To understand evolutionary factors that maintain complex trait variation, we sequenced genomes from a single population of the plant Mimulus guttatus, identifying hundreds of nucleotide variants associated with morphological and life history traits. Alleles that delayed flowering also increased size at reproduction, which suggests pervasive antagonistic pleiotropy in this annual plant. The "large and slow" alleles, which were less common in small, rapidly flowering populations, became more abundant in populations with greater plant size. Furthermore, natural selection within the field population favored alternative alleles from year to year. Our results suggest that environmental fluctuations and selective trade-offs maintain polygenic trait variation within populations and also contribute to the geographic divergence in this wildflower species.}, } @article {pmid30072533, year = {2018}, author = {Goldford, JE and Lu, N and Bajić, D and Estrela, S and Tikhonov, M and Sanchez-Gorostiaga, A and Segrè, D and Mehta, P and Sanchez, A}, title = {Emergent simplicity in microbial community assembly.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {469-474}, doi = {10.1126/science.aat1168}, pmid = {30072533}, issn = {1095-9203}, support = {R01 DE024468/DE/NIDCR NIH HHS/United States ; R01 GM121950/GM/NIGMS NIH HHS/United States ; R35 GM119461/GM/NIGMS NIH HHS/United States ; T32 GM100842/GM/NIGMS NIH HHS/United States ; P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 GM089978/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*classification/isolation & purification/*metabolism ; *Microbial Consortia ; Plants/*microbiology ; *Soil Microbiology ; }, abstract = {A major unresolved question in microbiome research is whether the complex taxonomic architectures observed in surveys of natural communities can be explained and predicted by fundamental, quantitative principles. Bridging theory and experiment is hampered by the multiplicity of ecological processes that simultaneously affect community assembly in natural ecosystems. We addressed this challenge by monitoring the assembly of hundreds of soil- and plant-derived microbiomes in well-controlled minimal synthetic media. Both the community-level function and the coarse-grained taxonomy of the resulting communities are highly predictable and governed by nutrient availability, despite substantial species variability. By generalizing classical ecological models to include widespread nonspecific cross-feeding, we show that these features are all emergent properties of the assembly of large microbial communities, explaining their ubiquity in natural microbiomes.}, } @article {pmid30072532, year = {2018}, author = {Gittis, A}, title = {Probing new targets for movement disorders.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {462}, doi = {10.1126/science.aau4916}, pmid = {30072532}, issn = {1095-9203}, mesh = {Animals ; *Deep Brain Stimulation ; Disease Models, Animal ; Globus Pallidus/*physiopathology ; Humans ; Mice ; Parkinson Disease/*genetics/physiopathology/*therapy ; Subthalamic Nucleus/physiopathology ; }, } @article {pmid30072531, year = {2018}, author = {Grossman, N}, title = {Modulation without surgical intervention.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {461-462}, doi = {10.1126/science.aau4915}, pmid = {30072531}, issn = {1095-9203}, mesh = {Deep Brain Stimulation/*methods ; *Electromagnetic Fields ; Humans ; Motor Cortex/*physiology ; }, } @article {pmid30072530, year = {2018}, author = {Schluttenhofer, C}, title = {Canada begins a great ganja experiment.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {460}, doi = {10.1126/science.aau5323}, pmid = {30072530}, issn = {1095-9203}, mesh = {Biomedical Research/*trends ; Canada ; Humans ; Marijuana Use/*legislation & jurisprudence ; Policy ; }, } @article {pmid30072529, year = {2018}, author = {Artelle, KA and Moola, FM and Paquet, PC and Darimont, CT}, title = {British Columbia's wildlife model reform.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {459-460}, doi = {10.1126/science.aau6992}, pmid = {30072529}, issn = {1095-9203}, mesh = {Animals ; *Animals, Wild ; British Columbia ; Conservation of Natural Resources/*trends ; }, } @article {pmid30072528, year = {2018}, author = {Silveira, FAO and Ferreira, MC and Perillo, LN and Carmo, FF and Neves, FS}, title = {Brazil's protected areas under threat.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {459}, doi = {10.1126/science.aau4222}, pmid = {30072528}, issn = {1095-9203}, mesh = {*Biodiversity ; Brazil ; Conservation of Natural Resources/*legislation & jurisprudence ; Decision Making ; }, } @article {pmid30072527, year = {2018}, author = {Womble, P and Perrone, D and Jasechko, S and Nelson, RL and Szeptycki, LF and Anderson, RT and Gorelick, SM}, title = {Indigenous communities, groundwater opportunities.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {453-455}, doi = {10.1126/science.aat6041}, pmid = {30072527}, issn = {1095-9203}, } @article {pmid30072526, year = {2018}, author = {Wulff, BBH and Dhugga, KS}, title = {Wheat-the cereal abandoned by GM.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {451-452}, doi = {10.1126/science.aat5119}, pmid = {30072526}, issn = {1095-9203}, mesh = {Africa ; Asia ; Disease Resistance/*genetics ; Edible Grain/*genetics ; Food Supply ; *Food, Genetically Modified ; Fusarium ; Plant Diseases/*genetics/microbiology ; *Plants, Genetically Modified ; Triticum/*genetics ; }, } @article {pmid30072525, year = {2018}, author = {Fleming, SM and Bang, D}, title = {Shouldering responsibility.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {449-450}, doi = {10.1126/science.aau5392}, pmid = {30072525}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Humans ; *Leadership ; Neurobiology ; }, } @article {pmid30072524, year = {2018}, author = {Cullen-Unsworth, LC and Unsworth, R}, title = {A call for seagrass protection.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {446-448}, doi = {10.1126/science.aat7318}, pmid = {30072524}, issn = {1095-9203}, mesh = {*Aquatic Organisms ; Biodiversity ; *Conservation of Natural Resources ; *Magnoliopsida ; }, } @article {pmid30072523, year = {2018}, author = {Sokol, J}, title = {A place in the sun.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {441-445}, doi = {10.1126/science.361.6401.441}, pmid = {30072523}, issn = {1095-9203}, } @article {pmid30072522, year = {2018}, author = {Normile, D}, title = {Staying slim during pregnancy carries a price.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {440}, doi = {10.1126/science.361.6401.440}, pmid = {30072522}, issn = {1095-9203}, mesh = {Female ; Humans ; *Infant, Low Birth Weight ; Japan/epidemiology ; Pregnancy ; Pregnancy Complications/*epidemiology ; Thinness/*epidemiology ; Weight Gain ; Weight Loss ; }, } @article {pmid30072521, year = {2018}, author = {Gibbons, A}, title = {How islands shrink people.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {439}, doi = {10.1126/science.361.6401.439}, pmid = {30072521}, issn = {1095-9203}, mesh = {Anthropology, Physical ; Asian Continental Ancestry Group/genetics ; DNA/genetics ; Dwarfism/*genetics ; Humans ; Indonesia ; *Islands ; Polymorphism, Genetic ; Selection, Genetic ; }, } @article {pmid30072520, year = {2018}, author = {Cohen, J}, title = {'Ending AIDS' movement falters worldwide.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {438}, doi = {10.1126/science.361.6401.438}, pmid = {30072520}, issn = {1095-9203}, mesh = {Acquired Immunodeficiency Syndrome/*epidemiology/*prevention & control ; *Disease Eradication ; *Global Health ; Health Promotion/*trends ; Humans ; United Nations ; }, } @article {pmid30072519, year = {2018}, author = {Erard, M and Matacic, C}, title = {Did kindness prime our species for language?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {436-437}, doi = {10.1126/science.361.6401.436}, pmid = {30072519}, issn = {1095-9203}, mesh = {Animals ; *Domestication ; Emotions/*physiology ; Finches/*physiology ; Humans ; *Language ; *Language Development ; Vocalization, Animal/*physiology ; }, } @article {pmid30072518, year = {2018}, author = {Kupferschmidt, K}, title = {EU verdict on CRISPR crops dismays scientists.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {435-436}, doi = {10.1126/science.361.6401.435}, pmid = {30072518}, issn = {1095-9203}, mesh = {*CRISPR-Cas Systems ; Clustered Regularly Interspaced Short Palindromic Repeats ; Crops, Agricultural/*genetics ; European Union ; Gene Editing/*legislation & jurisprudence ; Plants, Genetically Modified/*genetics ; }, } @article {pmid30072517, year = {2018}, author = {, }, title = {Researchers welcome Trump's pick to head science office.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {434}, doi = {10.1126/science.361.6401.434}, pmid = {30072517}, issn = {1095-9203}, } @article {pmid30072515, year = {2018}, author = {Thaler, RH}, title = {Nudge, not sludge.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {431}, doi = {10.1126/science.aau9241}, pmid = {30072515}, issn = {1095-9203}, } @article {pmid30072514, year = {2018}, author = {}, title = {Erratum for the Report "Synapse-specific representation of the identity of overlapping memory engrams" by K. Abdou, M. Shehata, K. Choko, H. Nishizono, M. Matsuo, S. Muramatsu, K. Inokuchi.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {}, doi = {10.1126/science.aau8829}, pmid = {30072514}, issn = {1095-9203}, } @article {pmid30072513, year = {2018}, author = {Bay, RA and Harrigan, RJ and Buermann, W and Underwood, VL and Gibbs, HL and Smith, TB and Ruegg, K}, title = {Response to Comment on "Genomic signals of selection predict climate-driven population declines in a migratory bird".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {}, doi = {10.1126/science.aat7956}, pmid = {30072513}, issn = {1095-9203}, mesh = {Animals ; *Climate ; *Climate Change ; Genome ; Genomics ; Passeriformes ; }, abstract = {Fitzpatrick et al discuss issues that they had with analyses and interpretation in our recent manuscript on genomic correlates of climate in yellow warblers. We provide evidence that our findings would not change with different analysis and maintain that our study represents a promising direction for integrating the potential for climate adaptation as one of many tools in conservation management.}, } @article {pmid30072512, year = {2018}, author = {Gut, G and Herrmann, MD and Pelkmans, L}, title = {Multiplexed protein maps link subcellular organization to cellular states.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {}, doi = {10.1126/science.aar7042}, pmid = {30072512}, issn = {1095-9203}, mesh = {Cell Cycle ; Cell Nucleus ; Cell Shape ; Cytoskeleton/ultrastructure ; *Fluorescent Antibody Technique, Indirect ; HeLa Cells ; Humans ; Organelles/ultrastructure ; *Protein Interaction Maps ; Single-Cell Analysis/*methods ; }, abstract = {Obtaining highly multiplexed protein measurements across multiple length scales has enormous potential for biomedicine. Here, we measured, by iterative indirect immunofluorescence imaging (4i), 40-plex protein readouts from biological samples at high-throughput from the millimeter to the nanometer scale. This approach simultaneously captures properties apparent at the population, cellular, and subcellular levels, including microenvironment, cell shape, and cell cycle state. It also captures the detailed morphology of organelles, cytoskeletal structures, nuclear subcompartments, and the fate of signaling receptors in thousands of single cells in situ. We used computer vision and systems biology approaches to achieve unsupervised comprehensive quantification of protein subcompartmentalization within various multicellular, cellular, and pharmacological contexts. Thus, highly multiplexed subcellular protein maps can be used to identify functionally relevant single-cell states.}, } @article {pmid30072511, year = {2018}, author = {Wu, H and Carvalho, P and Voeltz, GK}, title = {Here, there, and everywhere: The importance of ER membrane contact sites.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {}, doi = {10.1126/science.aan5835}, pmid = {30072511}, issn = {1095-9203}, mesh = {Animals ; Calcium/metabolism ; Cell Membrane/*metabolism/ultrastructure ; Endoplasmic Reticulum/*metabolism/ultrastructure ; Endosomes/metabolism/ultrastructure ; Humans ; Lipid Droplets/metabolism ; Lipid Metabolism ; Metabolic Networks and Pathways ; Microscopy, Fluorescence ; Mitochondria/metabolism/ultrastructure ; Neurodegenerative Diseases/metabolism ; Peroxisomes/metabolism/ultrastructure ; Vesicular Transport Proteins/chemistry/metabolism ; }, abstract = {Our textbook image of organelles has changed. Instead of revealing isolated cellular compartments, the picture now emerging shows organelles as largely interdependent structures that can communicate through membrane contact sites (MCSs). MCSs are sites where opposing organelles are tethered but do not fuse. MCSs provide a hybrid location where the tool kits of two different organelles can work together to perform vital cellular functions, such as lipid and ion transfer, signaling, and organelle division. Here, we focus on MCSs involving the endoplasmic reticulum (ER), an organelle forming an extensive network of cisternae and tubules. We highlight how the dynamic ER network regulates a plethora of cellular processes through MCSs with various organelles and with the plasma membrane.}, } @article {pmid30072510, year = {2018}, author = {Edelson, MG and Polania, R and Ruff, CC and Fehr, E and Hare, TA}, title = {Computational and neurobiological foundations of leadership decisions.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {}, doi = {10.1126/science.aat0036}, pmid = {30072510}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Adult ; Brain/*physiology ; Choice Behavior/*physiology ; Computer Simulation ; Decision Making/*physiology ; Female ; Humans ; *Leadership ; Magnetic Resonance Imaging ; Male ; Models, Psychological ; Nerve Net/*physiology ; *Social Responsibility ; }, abstract = {Leaders must take responsibility for others and thus affect the well-being of individuals, organizations, and nations. We identify the effects of responsibility on leaders' choices at the behavioral and neurobiological levels and document the widespread existence of responsibility aversion, that is, a reduced willingness to make decisions if the welfare of others is at stake. In mechanistic terms, basic preferences toward risk, loss, and ambiguity do not explain responsibility aversion, which, instead, is driven by a second-order cognitive process reflecting an increased demand for certainty about the best choice when others' welfare is affected. Finally, models estimating levels of information flow between brain regions that process separate choice components provide the first step in understanding the neurobiological basis of individual variability in responsibility aversion and leadership scores.}, } @article {pmid30072435, year = {2018}, author = {Bolze, A and Boisson, B and Bosch, B and Antipenko, A and Bouaziz, M and Sackstein, P and Chaker-Margot, M and Barlogis, V and Briggs, T and Colino, E and Elmore, AC and Fischer, A and Genel, F and Hewlett, A and Jedidi, M and Kelecic, J and Krüger, R and Ku, CL and Kumararatne, D and Lefevre-Utile, A and Loughlin, S and Mahlaoui, N and Markus, S and Garcia, JM and Nizon, M and Oleastro, M and Pac, M and Picard, C and Pollard, AJ and Rodriguez-Gallego, C and Thomas, C and Von Bernuth, H and Worth, A and Meyts, I and Risolino, M and Selleri, L and Puel, A and Klinge, S and Abel, L and Casanova, JL}, title = {Incomplete penetrance for isolated congenital asplenia in humans with mutations in translated and untranslated RPSA exons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8007-E8016}, pmid = {30072435}, issn = {1091-6490}, support = {UL1 TR001866/TR/NCATS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {5' Untranslated Regions ; *Exons ; Female ; Founder Effect ; Heterozygote ; Humans ; Immunologic Deficiency Syndromes/*genetics/metabolism ; Male ; *Mutation ; *Penetrance ; Protein Biosynthesis/*genetics ; RNA Splicing/*genetics ; Receptors, Laminin/biosynthesis/*genetics ; Ribosomal Proteins/biosynthesis/*genetics ; Spleen/*abnormalities/metabolism ; }, abstract = {Isolated congenital asplenia (ICA) is the only known human developmental defect exclusively affecting a lymphoid organ. In 2013, we showed that private deleterious mutations in the protein-coding region of RPSA, encoding ribosomal protein SA, caused ICA by haploinsufficiency with complete penetrance. We reported seven heterozygous protein-coding mutations in 8 of the 23 kindreds studied, including 6 of the 8 multiplex kindreds. We have since enrolled 33 new kindreds, 5 of which are multiplex. We describe here 11 new heterozygous ICA-causing RPSA protein-coding mutations, and the first two mutations in the 5'-UTR of this gene, which disrupt mRNA splicing. Overall, 40 of the 73 ICA patients (55%) and 23 of the 56 kindreds (41%) carry mutations located in translated or untranslated exons of RPSA. Eleven of the 43 kindreds affected by sporadic disease (26%) carry RPSA mutations, whereas 12 of the 13 multiplex kindreds (92%) carry RPSA mutations. We also report that 6 of 18 (33%) protein-coding mutations and the two (100%) 5'-UTR mutations display incomplete penetrance. Three mutations were identified in two independent kindreds, due to a hotspot or a founder effect. Finally, RPSA ICA-causing mutations were demonstrated to be de novo in 7 of the 23 probands. Mutations in RPSA exons can affect the translated or untranslated regions and can underlie ICA with complete or incomplete penetrance.}, } @article {pmid30072434, year = {2018}, author = {Karp, DS and Chaplin-Kramer, R and Meehan, TD and Martin, EA and DeClerck, F and Grab, H and Gratton, C and Hunt, L and Larsen, AE and Martínez-Salinas, A and O'Rourke, ME and Rusch, A and Poveda, K and Jonsson, M and Rosenheim, JA and Schellhorn, NA and Tscharntke, T and Wratten, SD and Zhang, W and Iverson, AL and Adler, LS and Albrecht, M and Alignier, A and Angelella, GM and Zubair Anjum, M and Avelino, J and Batáry, P and Baveco, JM and Bianchi, FJJA and Birkhofer, K and Bohnenblust, EW and Bommarco, R and Brewer, MJ and Caballero-López, B and Carrière, Y and Carvalheiro, LG and Cayuela, L and Centrella, M and Ćetković, A and Henri, DC and Chabert, A and Costamagna, AC and De la Mora, A and de Kraker, J and Desneux, N and Diehl, E and Diekötter, T and Dormann, CF and Eckberg, JO and Entling, MH and Fiedler, D and Franck, P and Frank van Veen, FJ and Frank, T and Gagic, V and Garratt, MPD and Getachew, A and Gonthier, DJ and Goodell, PB and Graziosi, I and Groves, RL and Gurr, GM and Hajian-Forooshani, Z and Heimpel, GE and Herrmann, JD and Huseth, AS and Inclán, DJ and Ingrao, AJ and Iv, P and Jacot, K and Johnson, GA and Jones, L and Kaiser, M and Kaser, JM and Keasar, T and Kim, TN and Kishinevsky, M and Landis, DA and Lavandero, B and Lavigne, C and Le Ralec, A and Lemessa, D and Letourneau, DK and Liere, H and Lu, Y and Lubin, Y and Luttermoser, T and Maas, B and Mace, K and Madeira, F and Mader, V and Cortesero, AM and Marini, L and Martinez, E and Martinson, HM and Menozzi, P and Mitchell, MGE and Miyashita, T and Molina, GAR and Molina-Montenegro, MA and O'Neal, ME and Opatovsky, I and Ortiz-Martinez, S and Nash, M and Östman, Ö and Ouin, A and Pak, D and Paredes, D and Parsa, S and Parry, H and Perez-Alvarez, R and Perović, DJ and Peterson, JA and Petit, S and Philpott, SM and Plantegenest, M and Plećaš, M and Pluess, T and Pons, X and Potts, SG and Pywell, RF and Ragsdale, DW and Rand, TA and Raymond, L and Ricci, B and Sargent, C and Sarthou, JP and Saulais, J and Schäckermann, J and Schmidt, NP and Schneider, G and Schüepp, C and Sivakoff, FS and Smith, HG and Stack Whitney, K and Stutz, S and Szendrei, Z and Takada, MB and Taki, H and Tamburini, G and Thomson, LJ and Tricault, Y and Tsafack, N and Tschumi, M and Valantin-Morison, M and Van Trinh, M and van der Werf, W and Vierling, KT and Werling, BP and Wickens, JB and Wickens, VJ and Woodcock, BA and Wyckhuys, K and Xiao, H and Yasuda, M and Yoshioka, A and Zou, Y}, title = {Crop pests and predators exhibit inconsistent responses to surrounding landscape composition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7863-E7870}, pmid = {30072434}, issn = {1091-6490}, mesh = {Animals ; *Crops, Agricultural/growth & development/parasitology ; *Ecosystem ; *Models, Biological ; *Pest Control, Biological ; }, abstract = {The idea that noncrop habitat enhances pest control and represents a win-win opportunity to conserve biodiversity and bolster yields has emerged as an agroecological paradigm. However, while noncrop habitat in landscapes surrounding farms sometimes benefits pest predators, natural enemy responses remain heterogeneous across studies and effects on pests are inconclusive. The observed heterogeneity in species responses to noncrop habitat may be biological in origin or could result from variation in how habitat and biocontrol are measured. Here, we use a pest-control database encompassing 132 studies and 6,759 sites worldwide to model natural enemy and pest abundances, predation rates, and crop damage as a function of landscape composition. Our results showed that although landscape composition explained significant variation within studies, pest and enemy abundances, predation rates, crop damage, and yields each exhibited different responses across studies, sometimes increasing and sometimes decreasing in landscapes with more noncrop habitat but overall showing no consistent trend. Thus, models that used landscape-composition variables to predict pest-control dynamics demonstrated little potential to explain variation across studies, though prediction did improve when comparing studies with similar crop and landscape features. Overall, our work shows that surrounding noncrop habitat does not consistently improve pest management, meaning habitat conservation may bolster production in some systems and depress yields in others. Future efforts to develop tools that inform farmers when habitat conservation truly represents a win-win would benefit from increased understanding of how landscape effects are modulated by local farm management and the biology of pests and their enemies.}, } @article {pmid30072433, year = {2018}, author = {Jack, BK and Jayachandran, S}, title = {Self-selection into payments for ecosystem services programs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802868115}, pmid = {30072433}, issn = {1091-6490}, abstract = {Designers and funders of payments for ecosystem services (PES) programs have long worried that payments flow to landholders who would have conserved forests even without the program, undermining the environmental benefits ("additionality") and cost-effectiveness of PES. If landholders self-select into PES programs based on how much conservation they were going to undertake anyway, then those who were planning to conserve should always enroll. This paper discusses the less-appreciated fact that enrollment is often based on other factors too. The hassle of signing up or financial costs of enrollment (e.g., purchasing seedlings) can affect who participates in a PES program. These enrollment costs reduce overall take-up, and, importantly, they can also influence the composition of landholders who select into the program-and thereby the program's environmental benefits per enrollee. Enrollment costs can increase a program's benefits per enrollee if they are systematically higher for (and thus deter enrollment by) landholders who would have conserved anyway. Alternatively, enrollment costs can dampen per-enrollee benefits if their correlation with status-quo conservation is in the opposite direction. We illustrate these points with evidence from two studies of randomized trials of PES programs aimed at increasing forest cover in Uganda and Malawi. We also discuss how in other sectors, such as social welfare, policy designers have purposefully adjusted the costs of program enrollment to influence the composition of participants and improve cost-effectiveness. We propose that these ideas for targeting could be incorporated into the design of PES programs.}, } @article {pmid30072432, year = {2018}, author = {Settele, J and Settle, WH}, title = {Conservation biological control: Improving the science base.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8241-8243}, pmid = {30072432}, issn = {1091-6490}, mesh = {*Biodiversity ; *Conservation of Natural Resources ; }, } @article {pmid30072431, year = {2018}, author = {Liebmann, M and Hucke, S and Koch, K and Eschborn, M and Ghelman, J and Chasan, AI and Glander, S and Schädlich, M and Kuhlencord, M and Daber, NM and Eveslage, M and Beyer, M and Dietrich, M and Albrecht, P and Stoll, M and Busch, KB and Wiendl, H and Roth, J and Kuhlmann, T and Klotz, L}, title = {Nur77 serves as a molecular brake of the metabolic switch during T cell activation to restrict autoimmunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E8017-E8026}, pmid = {30072431}, issn = {1091-6490}, mesh = {Animals ; *Autoimmunity ; Central Nervous System/immunology/metabolism ; Gene Expression Profiling ; Inflammation/genetics/immunology/metabolism ; *Lymphocyte Activation ; Mice ; Mice, Knockout ; *Mitochondria/genetics/immunology/metabolism ; *Nuclear Receptor Subfamily 4, Group A, Member 1/genetics/immunology/metabolism ; Oxygen Consumption/*immunology ; Receptors, Estrogen/genetics/immunology/metabolism ; *T-Lymphocytes/immunology/metabolism ; }, abstract = {T cells critically depend on reprogramming of metabolic signatures to meet the bioenergetic demands during activation and clonal expansion. Here we identify the transcription factor Nur77 as a cell-intrinsic modulator of T cell activation. Nur77-deficient T cells are highly proliferative, and lack of Nur77 is associated with enhanced T cell activation and increased susceptibility for T cell-mediated inflammatory diseases, such as CNS autoimmunity, allergic contact dermatitis and collagen-induced arthritis. Importantly, Nur77 serves as key regulator of energy metabolism in T cells, restricting mitochondrial respiration and glycolysis and controlling switching between different energy pathways. Transcriptional network analysis revealed that Nur77 modulates the expression of metabolic genes, most likely in close interaction with other transcription factors, especially estrogen-related receptor α. In summary, we identify Nur77 as a transcriptional regulator of T cell metabolism, which elevates the threshold for T cell activation and confers protection in different T cell-mediated inflammatory diseases.}, } @article {pmid30072430, year = {2018}, author = {Crowe, JL and Shao, Z and Wang, XS and Wei, PC and Jiang, W and Lee, BJ and Estes, VM and Alt, FW and Zha, S}, title = {Kinase-dependent structural role of DNA-PKcs during immunoglobulin class switch recombination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8615-8620}, pmid = {30072430}, issn = {1091-6490}, support = {R01 CA158073/CA/NCI NIH HHS/United States ; R01 CA184187/CA/NCI NIH HHS/United States ; F31 CA183504/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; TL1 TR000082/TR/NCATS NIH HHS/United States ; R01 CA215067/CA/NCI NIH HHS/United States ; P01 CA174653/CA/NCI NIH HHS/United States ; R01 AI077595/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; B-Lymphocytes/cytology/*enzymology ; Cell Line ; DNA-Activated Protein Kinase/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Immunoglobulin Class Switching/*physiology ; Immunoglobulin G/*biosynthesis/genetics ; Mice ; Mice, Knockout ; Nuclear Proteins/genetics/*metabolism ; Recombination, Genetic/*physiology ; }, abstract = {The catalytic subunit of DNA-dependent protein kinase (DNA-PKcs) is a classical nonhomologous end-joining (cNHEJ) factor. Loss of DNA-PKcs diminished mature B cell class switch recombination (CSR) to other isotypes, but not IgG1. Here, we show that expression of the kinase-dead DNA-PKcs (DNA-PKcsKD/KD) severely compromises CSR to IgG1. High-throughput sequencing analyses of CSR junctions reveal frequent accumulation of nonproductive interchromosomal translocations, inversions, and extensive end resection in DNA-PKcsKD/KD , but not DNA-PKcs-/- , B cells. Meanwhile, the residual joints from DNA-PKcsKD/KD cells and the efficient Sµ-Sγ1 junctions from DNA-PKcs-/- B cells both display similar preferences for small (2-6 nt) microhomologies (MH). In DNA-PKcs-/- cells, Sµ-Sγ1 joints are more resistant to inversions and extensive resection than Sµ-Sε and Sµ-Sµ joints, providing a mechanism for the isotype-specific CSR defects. Together, our findings identify a kinase-dependent role of DNA-PKcs in suppressing MH-mediated end joining and a structural role of DNA-PKcs protein in the orientation of CSR.}, } @article {pmid30072429, year = {2018}, author = {Mattar, P and Stevanovic, M and Nad, I and Cayouette, M}, title = {Casz1 controls higher-order nuclear organization in rod photoreceptors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7987-E7996}, pmid = {30072429}, issn = {1091-6490}, support = {PJT-148553//CIHR/Canada ; }, mesh = {Animals ; DNA-Binding Proteins/genetics/*metabolism ; Gene Silencing/physiology ; Heterochromatin/genetics/*metabolism ; Lamin Type A/genetics/*metabolism ; Mice ; Mice, Transgenic ; *Models, Biological ; Polycomb-Group Proteins/genetics/*metabolism ; Retinal Rod Photoreceptor Cells/cytology/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Genome organization plays a fundamental role in the gene-expression programs of numerous cell types, but determinants of higher-order genome organization are poorly understood. In the developing mouse retina, rod photoreceptors represent a good model to study this question. They undergo a process called "chromatin inversion" during differentiation, in which, as opposed to classic nuclear organization, heterochromatin becomes localized to the center of the nucleus and euchromatin is restricted to the periphery. While previous studies showed that the lamin B receptor participates in this process, the molecular mechanisms regulating lamina function during differentiation remain elusive. Here, using conditional genetics, we show that the zinc finger transcription factor Casz1 is required to establish and maintain the inverted chromatin organization of rod photoreceptors and to safeguard their gene-expression profile and long-term survival. At the mechanistic level, we show that Casz1 interacts with the polycomb repressor complex in a splice variant-specific manner and that both are required to suppress the expression of the nuclear envelope intermediate filament lamin A/C in rods. Lamin A is in turn sufficient to regulate heterochromatin organization and nuclear position. Furthermore, we show that Casz1 is sufficient to expand and centralize the heterochromatin of fibroblasts, suggesting a general role for Casz1 in nuclear organization. Together, these data support a model in which Casz1 cooperates with polycomb to control rod genome organization, in part by silencing lamin A/C.}, } @article {pmid30072428, year = {2018}, author = {Amato, R and Lacasa, L and Díaz-Guilera, A and Baronchelli, A}, title = {The dynamics of norm change in the cultural evolution of language.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8260-8265}, pmid = {30072428}, issn = {1091-6490}, mesh = {*Cultural Evolution ; Humans ; *Language ; *Social Norms ; }, abstract = {What happens when a new social convention replaces an old one? While the possible forces favoring norm change-such as institutions or committed activists-have been identified for a long time, little is known about how a population adopts a new convention, due to the difficulties of finding representative data. Here, we address this issue by looking at changes that occurred to 2,541 orthographic and lexical norms in English and Spanish through the analysis of a large corpora of books published between the years 1800 and 2008. We detect three markedly distinct patterns in the data, depending on whether the behavioral change results from the action of a formal institution, an informal authority, or a spontaneous process of unregulated evolution. We propose a simple evolutionary model able to capture all of the observed behaviors, and we show that it reproduces quantitatively the empirical data. This work identifies general mechanisms of norm change, and we anticipate that it will be of interest to researchers investigating the cultural evolution of language and, more broadly, human collective behavior.}, } @article {pmid30072217, year = {2018}, author = {Hirt, MR and Grimm, V and Li, Y and Rall, BC and Rosenbaum, B and Brose, U}, title = {Bridging Scales: Allometric Random Walks Link Movement and Biodiversity Research.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {701-712}, doi = {10.1016/j.tree.2018.07.003}, pmid = {30072217}, issn = {1872-8383}, abstract = {Integrating mechanistic models of movement and behavior into large-scale movement ecology and biodiversity research is one of the major challenges in current ecological science. This is mainly due to a large gap between the spatial scales at which these research lines act. Here, we propose to apply trait-based movement models to bridge this gap and generalize movement trajectories across species and ecosystems. We show how to use species traits (e.g., body mass) to generate allometric random walks and illustrate in two worked examples how this facilitates general predictions of species-interaction traits, meta-community structures, and biodiversity patterns. Thereby, allometric random walks foster a closer integration of movement ecology and biodiversity research by scaling up from small-scale mechanistic measurements to a predictive understanding of movement and biodiversity patterns in different landscapes.}, } @article {pmid30072187, year = {2018}, author = {Stephens, NB and Kivell, TL and Pahr, DH and Hublin, JJ and Skinner, MM}, title = {Trabecular bone patterning across the human hand.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {1-23}, doi = {10.1016/j.jhevol.2018.05.004}, pmid = {30072187}, issn = {1095-8606}, abstract = {Hand bone morphology is regularly used to link particular hominin species with behaviors relevant to cognitive/technological progress. Debates about the functional significance of differing hominin hand bone morphologies tend to rely on establishing phylogenetic relationships and/or inferring behavior from epigenetic variation arising from mechanical loading and adaptive bone modeling. Most research focuses on variation in cortical bone structure, but additional information about hand function may be provided through the analysis of internal trabecular structure. While primate hand bone trabecular structure is known to vary in ways that are consistent with expected joint loading differences during manipulation and locomotion, no study exists that has documented this variation across the numerous bones of the hand. We quantify the trabecular structure in 22 bones of the human hand (early/extant modern Homo sapiens) and compare structural variation between two groups associated with post-agricultural/industrial (post-Neolithic) and foraging/hunter-gatherer (forager) subsistence strategies. We (1) establish trabecular bone volume fraction (BV/TV), modulus (E), degree of anisotropy (DA), mean trabecular thickness (Tb.Th) and spacing (Tb.Sp); (2) visualize the average distribution of site-specific BV/TV for each bone; and (3) examine if the variation in trabecular structure is consistent with expected joint loading differences among the regions of the hand and between the groups. Results indicate similar distributions of trabecular bone in both groups, with those of the forager sample presenting higher BV/TV, E, and lower DA, suggesting greater and more variable loading during manipulation. We find indications of higher loading along the ulnar side of the forager sample hand, with high site-specific BV/TV distributions among the carpals that are suggestive of high loading while the wrist moves through the 'dart-thrower's' motion. These results support the use of trabecular structure to infer behavior and have direct implications for refining our understanding of human hand evolution and fossil hominin hand use.}, } @article {pmid30072086, year = {2018}, author = {Brunker, K and Mollentze, N}, title = {Rabies Virus.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {886-887}, doi = {10.1016/j.tim.2018.07.001}, pmid = {30072086}, issn = {1878-4380}, abstract = {This infographic describes the transmission cycle of rabies virus in domestic dogs and the necessity of a One Health approach, integrating medical and veterinary interventions, to control and eliminate human rabies deaths. Rabies virus (RABV) causes an acute, fatal neurological infection in humans and other mammals, transmitted through the saliva of rabid animals via a bite or scratch. From the site of infection the virus travels along neurons to the central nervous system (CNS), where viral replication leads to symptoms and systemic spread. Once symptomatic, the disease is nearly 100% fatal. However, the disease is 100% vaccine-preventable through the prompt administration of human postexposure prophylaxis (PEP) and vaccination of animal reservoirs. While RABV has a broad host range, domestic dogs cause over 99% of all human cases, killing 59000 people every year. Human PEP is costly (US$11-150 per dose) and often difficult to obtain. Dog vaccination is a considerably more cost-effective and feasible method to reduce the incidence of human rabies. With this in mind, the World Health Organisation (WHO) and partners have set a target for the global elimination of dog-mediated human rabies, through control of the disease in dogs, by 2030.}, } @article {pmid30071904, year = {2018}, author = {Just, S and Mondot, S and Ecker, J and Wegner, K and Rath, E and Gau, L and Streidl, T and Hery-Arnaud, G and Schmidt, S and Lesker, TR and Bieth, V and Dunkel, A and Strowig, T and Hofmann, T and Haller, D and Liebisch, G and Gérard, P and Rohn, S and Lepage, P and Clavel, T}, title = {The gut microbiota drives the impact of bile acids and fat source in diet on mouse metabolism.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {134}, pmid = {30071904}, issn = {2049-2618}, mesh = {Amino Acids/metabolism ; Animals ; Bacteria/*classification/drug effects/genetics ; Bile Acids and Salts/*analysis ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Diet, High-Fat/*adverse effects ; Dietary Fats/adverse effects ; Gastrointestinal Microbiome/*drug effects ; Gene Expression Profiling ; Lipid Metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Obesity/*chemically induced/metabolism ; Palm Oil/adverse effects ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: As the gut microbiota contributes to metabolic health, it is important to determine specific diet-microbiota interactions that influence host metabolism. Bile acids and dietary fat source can alter phenotypes of diet-induced obesity, but the interplay with intestinal microorganisms is unclear. Here, we investigated metabolic consequences of diets enriched in primary bile acids with or without addition of lard or palm oil, and studied gut microbiota structure and functions in mice.

RESULTS: In combination with bile acids, dietary lard fed to male C57BL/6N mice for a period of 8 weeks enhanced fat mass accumulation in colonized, but not in germ-free mice when compared to palm oil. This was associated with impaired glucose tolerance, lower fasting insulin levels, lower counts of enteroendocrine cells, fatty liver, and elevated amounts of hepatic triglycerides, cholesteryl esters, and monounsaturated fatty acids. Lard- and bile acid-fed mice were characterized by shifts in dominant gut bacterial communities, including decreased relative abundances of Lachnospiraceae and increased occurrence of Desulfovibrionaceae and the species Clostridium lactatifermentans and Flintibacter butyricus. Metatranscriptomic analysis revealed shifts in microbial functions, including lipid and amino acid metabolism.

CONCLUSIONS: Caution is required when interpreting data from diet-induced obesity models due to varying effects of dietary fat source. Detrimental metabolic consequences of a diet enriched with lard and primary bile acids were dependent on microbial colonization of the host and were linked to hepatic lipid rearrangements and to alterations of dominant bacterial communities in the cecum.}, } @article {pmid30071894, year = {2018}, author = {Grimaldi, R and Gibson, GR and Vulevic, J and Giallourou, N and Castro-Mejía, JL and Hansen, LH and Leigh Gibson, E and Nielsen, DS and Costabile, A}, title = {A prebiotic intervention study in children with autism spectrum disorders (ASDs).}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {133}, pmid = {30071894}, issn = {2049-2618}, mesh = {Autism Spectrum Disorder/*diet therapy/microbiology/urine ; Bacteria/*classification/isolation & purification ; Child ; Child, Preschool ; Double-Blind Method ; Feces/chemistry/microbiology ; Female ; Gastrointestinal Tract/*microbiology ; Humans ; Male ; Prebiotics/*administration & dosage ; Urine/chemistry/microbiology ; }, abstract = {BACKGROUND: Different dietary approaches, such as gluten and casein free diets, or the use of probiotics and prebiotics have been suggested in autistic spectrum disorders in order to reduce gastrointestinal (GI) disturbances. GI symptoms are of particular interest in this population due to prevalence and correlation with the severity of behavioural traits. Nowadays, there is lack of strong evidence about the effect of dietary interventions on these problems, particularly prebiotics. Therefore, we assessed the impact of exclusion diets and a 6-week Bimuno® galactooligosaccharide (B-GOS®) prebiotic intervention in 30 autistic children.

RESULTS: The results showed that children on exclusion diets reported significantly lower scores of abdominal pain and bowel movement, as well as lower abundance of Bifidobacterium spp. and Veillonellaceae family, but higher presence of Faecalibacterium prausnitzii and Bacteroides spp. In addition, significant correlations were found between bacterial populations and faecal amino acids in this group, compared to children following an unrestricted diet. Following B-GOS® intervention, we observed improvements in anti-social behaviour, significant increase of Lachnospiraceae family, and significant changes in faecal and urine metabolites.

CONCLUSIONS: To our knowledge, this is the first study where the effect of exclusion diets and prebiotics has been evaluated in autism, showing potential beneficial effects. A combined dietary approach resulted in significant changes in gut microbiota composition and metabolism suggesting that multiple interventions might be more relevant for the improvement of these aspects as well as psychological traits.

TRIAL REGISTRATION: NCT02720900 ; registered in November 2015.}, } @article {pmid30071891, year = {2018}, author = {Indika, NLR and Kesavan, T and Dilanthi, HW and Jayasena, KLSPKM and Chandrasiri, NDPD and Jayasinghe, IN and Piumika, UMT and Vidanapathirana, DM and Gunarathne, KDAV and Dissanayake, M and Jasinge, E and Arachchi, WK and Doheny, D and Desnick, RJ}, title = {Many pitfalls in diagnosis of acute intermittent porphyria: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {552}, pmid = {30071891}, issn = {1756-0500}, mesh = {Adult ; DNA Mutational Analysis ; Genetic Testing ; Humans ; Hydroxymethylbilane Synthase ; Male ; Porphyria, Acute Intermittent/*diagnosis/genetics ; Sri Lanka ; }, abstract = {BACKGROUND: Acute intermittent porphyria is a rare autosomal dominant disorder caused by a deficiency of the enzyme, hydroxymethylbilane synthase. Recognition of acute neurovisceral attacks can be difficult due to the nonspecific nature of symptoms.

CASE PRESENTATION: We report a case of 33-year-old male patient who presented with recurrent episodes of severe abdominal pain, nausea, vomiting, constipation and numbness of bilateral lower limb extremities. These nonspecific neurovisceral attacks were subject to medical and surgical misdiagnoses of acute appendicitis, sinus tachycardia, renal calculi, drug-induced acute interstitial nephritis and two episodes of partial intestinal obstruction. The sixth acute attack raised the suspicion of an acute porphyria. Watson and Schwartz test was positive for porphobilinogen in urine. Mutation analysis by DNA sequencing of the extracted DNA of the proband revealed a previously reported missense mutation, c.517C>T encoding p.R173W in the HMBS gene, confirming the diagnosis of Acute Intermittent Porphyria. Four out of five family members who underwent targeted mutation analyses were mutation-positive.

CONCLUSION: The most common clinical presentation of Acute Intermittent Porphyria is abdominal pain with neurovisceral manifestations which are common to several medical, psychiatric and surgical pathologies. This leads to underdiagnosis and misdiagnosis of this disorder, incorrect management, and severe complications. Therefore, a high index of suspicion and awareness of front line laboratory investigations are important for diagnosis. Definitive diagnosis enables implementation of strategies to prevent acute attacks, and also triggers genetic testing and genetic counseling of at-risk family members.}, } @article {pmid30071888, year = {2018}, author = {Mulyadi, and Sunnati, and Azhary, M and Yunus, F and Nurwidya, F}, title = {The correlation of age and body mass index with the level of both protease MMP3 and anti-protease TIMP-1 among Indonesian patients with chronic obstructive pulmonary disease: a preliminary findings.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {551}, pmid = {30071888}, issn = {1756-0500}, mesh = {Adaptor Proteins, Signal Transducing ; Aged ; *Body Mass Index ; Female ; Humans ; Indonesia ; Male ; Matrix Metalloproteinase 3/*metabolism ; Matrix Metalloproteinase 9 ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/*metabolism ; Tissue Inhibitor of Metalloproteinase-1/*metabolism ; }, abstract = {OBJECTIVES: Individuals with chronic obstructive pulmonary disease (COPD) are usually > 50 years of age and have a low body mass index (BMI). An imbalance between matrix metalloproteinases (MMPs), including MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1), play a role in tissue degradation of lung extracellular matrix among COPD individuals. The purpose of the present study was to correlate age and/or BMI with salivary levels of MMP-3 and TIMP-1 among Indonesian subjects with COPD.

RESULTS: Thirty COPD patients were recruited to undergo thorough physical assessment and saliva collection for evaluating TIMP-1 and MMP-3 levels using commercially available kits enzyme-linked immunosorbent assay method. The mean (standard deviation) participant age and BMI were 60.5 (8.13) years, and 23.1 (4.75) kg/m2, respectively. Furthermore, the mean (standard deviation) of TIMP-1 and MMP3 levels were 23.99 (6.85) ng/mL and 1.81 (1.167) μM, respectively. Age was negatively correlated with MMP-3 (P < 0.05), but not with TIMP-1 levels. Age and BMI were not correlated with TIMP-1 level (P > 0.05). Collectively, this study demonstrated that age has a negative correlation with the protease marker (i.e. MMP-3), but not the anti-protease marker (TIMP-1). BMI was not correlated with either protease/anti-protease marker among Indonesian subjects with COPD.}, } @article {pmid30071886, year = {2018}, author = {Hosoya, S and Kikuchi, K and Nagashima, H and Onodera, J and Sugimoto, K and Satoh, K and Matsuzaki, K and Yasugi, M and Nagano, AJ and Kumagayi, A and Ueda, K and Kurokawa, T}, title = {Assessment of genetic diversity in Coho salmon (Oncorhynchus kisutch) populations with no family records using ddRAD-seq.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {548}, pmid = {30071886}, issn = {1756-0500}, mesh = {Animals ; Breeding ; Female ; *Genetic Variation ; Genotype ; Japan ; Male ; Oncorhynchus kisutch/*genetics ; }, abstract = {OBJECTIVE: Selective breeding for desirable traits is becoming popular in aquaculture. In Miyagi prefecture, Japan, a selectively bred population of Coho salmon (Oncorhynchus kisutch) has been established with the original, randomly breeding population maintained separately. Since they have been bred without family records, the genetic diversity within these populations remains unknown. In this study, we estimated the genetic diversity and key quantitative genetic parameters such as heritability and genomic breeding value for body size traits by means of genomic best linear unbiased prediction to assess the genetic health of these populations.

RESULTS: Ninety-nine and 83 females from the selective and random groups, respectively, were genotyped at 2350 putative SNPs by means of double digest restriction associated DNA sequencing. The genetic diversity in the selectively bred group was low, as were the estimated heritability and prediction accuracy for length and weight (h2 = 0.26-0.28; accuracy = 0.34), compared to the randomly bred group (h2 = 0.50-0.60; accuracy = 0.51-0.54). Although the tested sample size was small, these results suggest that further selection is difficult for the selectively bred population, while there is some potential for the randomly bred group, especially with the aid of genomic information.}, } @article {pmid30071884, year = {2018}, author = {Bhalla, D}, title = {Availability and sufficiency of phenobarbital, an essential medication, in Bhutan: a survey of global and neuropsychiatric relevance.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {549}, pmid = {30071884}, issn = {1756-0500}, mesh = {Adolescent ; Aged ; Anticonvulsants/*supply & distribution ; Asia ; Bhutan ; Child ; Child, Preschool ; Epilepsy/drug therapy ; Female ; Humans ; Infant ; Infant, Newborn ; Male ; Phenobarbital/*supply & distribution ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: We aimed to provide a reliable evidence-based conclusion around manufacturing, import, availability and sufficiency of one essential medication, phenobarbital (PB) through our example location (Bhutan). The relevant details about manufacturing, import, annual quantity, dose strength were obtained.

RESULTS: There was no local manufacturing of PB and all other anti-seizure medications. A total of 1068 vials of PB 200 mg/mL inj and 489,350 tablets of PB30 mg (i.e. 14.6 kilos) was estimated to annually become available. Of this, 5.3 k (36.3%) was present at the basic health units (BHUs). The PB was absent at 26 (14.7%) BHUs. There was no availability of PB syrup. Treating supposed target of 50.0% of the 20.0% of the prevalent case-load (N = 4523) require 18.1 kilo of PB annually. To conclude, having or not the local manufacturing may or may not be a limitation. There is a need to overcome challenges of inappropriate dose strength, absent pediatric formulation, indirect cost, and low selling price of PB. The possible therapeutic participation of PB in managing disease conditions (like epilepsy) remains limited despite favorable safety and efficacy profile. Strengthening the availability of essential medications is essential to reduce the treatment gap and public health burden of treatable disease conditions.}, } @article {pmid30071883, year = {2018}, author = {Suriapperuma, T and Peiris, R and Mettananda, C and Premawardhena, A and Mettananda, S}, title = {Body iron status of children and adolescents with transfusion dependent β-thalassaemia: trends of serum ferritin and associations of optimal body iron control.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {547}, pmid = {30071883}, issn = {1756-0500}, mesh = {Adolescent ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; Ferritins ; Humans ; Iron/*deficiency ; Iron Chelating Agents ; Male ; Sri Lanka ; beta-Thalassemia/*complications ; }, abstract = {OBJECTIVE: This cross sectional study aims to describe the body iron status, trends of serum ferritin and associations of optimal body iron control in patients aged below 16 years with transfusion dependent β-thalassaemia attending Paediatric and Adolescent Thalassaemia Centres of the Colombo North Teaching Hospital of Sri Lanka.

RESULTS: Out of 54 children, 51% were males and a majority were aged 11-16 years; 83% had β-thalassaemia major while 13% had HbE β-thalassaemia. Mean serum ferritin was 1778(± 1458) µg/l and 29% had optimal serum ferritin (below 1000 µg/l). Trend of mean serum ferritin over time showed gradual decline between 2011 and 2017 and longitudinal trend of individual patients at yearly intervals showed gradual rise until 5 years of age and plateauing thereafter. All except two patients were receiving iron chelator medication of which the most commonly used was oral deferasirox (92%). The most common iron-related complications were short stature (24.1%) and pubertal delay (42.8% of > 14 years). None of the patients had hypothyroidism, hypoparathyroidism or diabetes. Optimal serum ferritin levels were significantly associated with the diagnosis of thalassaemia at a later age (23.6 vs 9.0 months) and higher family income (OR-4.81;95%CI 1.17-19.67) however was not associated with the age of the patient or duration of transfusion.}, } @article {pmid30071880, year = {2018}, author = {Kumar, VE and Cherupanakkal, C and Catherine, M and Kadhiravan, T and Parameswaran, N and Rajendiran, S and Pillai, AB}, title = {Endogenous gene selection for relative quantification PCR and IL6 transcript levels in the PBMC's of severe and non-severe dengue cases.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {550}, pmid = {30071880}, issn = {1756-0500}, support = {ID2012-1766//Indian Council of Medical Research/ ; }, mesh = {Dengue/diagnosis/*genetics ; *Gene Expression Profiling ; Humans ; India ; Interleukin-6/*metabolism ; Leukocytes, Mononuclear ; Prospective Studies ; Real-Time Polymerase Chain Reaction ; Reference Standards ; }, abstract = {OBJECTIVES: Dengue viral infection ranges from dengue fever to dengue haemorrhagic fever and lethal dengue shock syndrome. Currently no means are available to monitor the progression of disease. Real time PCR based gene expression analyses are used to find potential molecular markers for effective prediction of dengue clinical outcome. The accuracy of qPCR analysis is strongly dependent on transcript normalization using stably expressed endogenous genes, which if selected imprecisely can lead to misinterpreted results. We aimed to determine the best fit for endogenous gene among six genes namely COX, ACTB, GAPDH, HMBS, HPRT and B2M for dengue viral infection cases. Gene stability was inferred from qPCR data by normalizing with two algorithms geNorm and Normfinder and the rankings generated were validated by gene expression analysis against target gene IL-6.

RESULTS: Both the algorithms showed ACTB, HPRT, GAPDH as most stable genes. Normalizing with the stable genes revealed a significant fold change (p < .05) in IL-6 levels of .32, .52, .69, and .62 in non-dengue febrile illness, non severe, severe and All Dengue groups respectively compared to healthy controls. based on our study, we suggest ACTB with HPRT/GAPDH combination for normalization in qPCR for precise quantification of transcripts in dengue infected studies.}, } @article {pmid30071832, year = {2018}, author = {Berthenet, E and Yahara, K and Thorell, K and Pascoe, B and Meric, G and Mikhail, JM and Engstrand, L and Enroth, H and Burette, A and Megraud, F and Varon, C and Atherton, JC and Smith, S and Wilkinson, TS and Hitchings, MD and Falush, D and Sheppard, SK}, title = {A GWAS on Helicobacter pylori strains points to genetic variants associated with gastric cancer risk.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {84}, pmid = {30071832}, issn = {1741-7007}, support = {MR/L015080/1//Medical Research Council/United Kingdom ; MR/M501608/1//Medical Research Council/United Kingdom ; G0801929//Medical Research Council/United Kingdom ; BB/I02464X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Helicobacter pylori are stomach-dwelling bacteria that are present in about 50% of the global population. Infection is asymptomatic in most cases, but it has been associated with gastritis, gastric ulcers and gastric cancer. Epidemiological evidence shows that progression to cancer depends upon the host and pathogen factors, but questions remain about why cancer phenotypes develop in a minority of infected people. Here, we use comparative genomics approaches to understand how genetic variation amongst bacterial strains influences disease progression.

RESULTS: We performed a genome-wide association study (GWAS) on 173 H. pylori isolates from the European population (hpEurope) with known disease aetiology, including 49 from individuals with gastric cancer. We identified SNPs and genes that differed in frequency between isolates from patients with gastric cancer and those with gastritis. The gastric cancer phenotype was associated with the presence of babA and genes in the cag pathogenicity island, one of the major virulence determinants of H. pylori, as well as non-synonymous variations in several less well-studied genes. We devised a simple risk score based on the risk level of associated elements present, which has the potential to identify strains that are likely to cause cancer but will require refinement and validation.

CONCLUSION: There are a number of challenges to applying GWAS to bacterial infections, including the difficulty of obtaining matched controls, multiple strain colonization and the possibility that causative strains may not be present when disease is detected. Our results demonstrate that bacterial factors have a sufficiently strong influence on disease progression that even a small-scale GWAS can identify them. Therefore, H. pylori GWAS can elucidate mechanistic pathways to disease and guide clinical treatment options, including for asymptomatic carriers.}, } @article {pmid30071829, year = {2018}, author = {Petschner, P and Tamasi, V and Adori, C and Kirilly, E and Ando, RD and Tothfalusi, L and Bagdy, G}, title = {Gene expression analysis indicates reduced memory and cognitive functions in the hippocampus and increase in synaptic reorganization in the frontal cortex 3 weeks after MDMA administration in Dark Agouti rats.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {580}, pmid = {30071829}, issn = {1471-2164}, support = {MTA-SE Neuropsychopharmacology and Neurochemistry Research Group//Hungarian Academy of Sciences and Semmelweis University/ ; Grants KTIA_13_NAP-A-II/14 and 2017-1.2.1-NKP-2017-00002//Hungarian Brain Research Program/ ; Grant KTIA_NAP_13-1-2013-0001//National Development Agency/ ; ÚNKP-17-4-I-SE-8//New National Excellence Program of the Ministry of Human Capacities/ ; OTKA-PD 108297//Hungarian Scientific Research Fund/ ; }, mesh = {Animals ; Cognition/*drug effects ; Frontal Lobe/drug effects ; Gene Expression Profiling/*methods ; Gene Expression Regulation/drug effects ; Gene Regulatory Networks/drug effects ; Hippocampus/drug effects ; Male ; Memory/*drug effects ; Models, Animal ; N-Methyl-3,4-methylenedioxyamphetamine/*administration & dosage ; Oligonucleotide Array Sequence Analysis ; Rats ; Synapses ; }, abstract = {BACKGROUND: 3,4-methylenedioxymethamphetamine (MDMA, "ecstasy") is a widely used entactogenic drug known to impair cognitive functions on the long-run. Both hippocampal and frontal cortical regions have well established roles in behavior, memory formation and other cognitive tasks and damage of these regions is associated with altered behavior and cognitive functions frequently described in otherwise healthy MDMA users. Meanwhile, in post-traumatic stress disorder (PTSD) patients seem to benefit from therapeutic application of the drug, where damage in hippocampal cue extinction may play a role. The aim of this study was to examine the hippocampus, frontal cortex and dorsal raphe of Dark Agouti rats with gene expression arrays (Illumina RatRef bead arrays) looking for possible mechanisms and new candidates contributing to the consequences of a single dose of MDMA (15 mg/kg) 3 weeks earlier.

RESULTS: The number of differentially expressed genes in the hippocampus, frontal cortex and the dorsal raphe were 481, 155, and 15, respectively. Gene set enrichment analysis of the microarray data revealed reduced expression of 'memory' and 'cognition', 'dendrite development' and 'regulation of synaptic plasticity' gene sets in the hippocampus, parallel to the downregulation of CaMK II subunits, glutamate-, CB1 cannabinoid- and EphA4, EphA5, EphA6 receptors. Downregulated gene sets in the frontal cortex were related to protein synthesis, chromatin organization, transmembrane transport processes, while 'dendrite development', 'regulation of synaptic plasticity' and 'positive regulation of synapse assembly' gene sets were upregulated besides elevated levels of a CaMK II subunit and NMDA2B glutamate receptor. Changes in the dorsal raphe region were mild and in most cases not significant.

CONCLUSION: The present data raise the possibility of new synapse formation / synaptic reorganization in the frontal cortex 3 weeks after a single neurotoxic dose of MDMA. In contrast, a prolonged depression of new neurite formation in the hippocampus is proposed by downregulations of members in long-term potentiation pathway and synaptic plasticity emphasizing the particular vulnerability of this brain region and proposing a mechanism responsible for cognitive problems in healthy individuals. At the same time, these results underpin benefits of MDMA in PTSD, where the drug may help memory extinction.}, } @article {pmid30071827, year = {2018}, author = {Mason, VC and Schaefer, RJ and McCue, ME and Leeb, T and Gerber, V}, title = {eQTL discovery and their association with severe equine asthma in European Warmblood horses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {581}, pmid = {30071827}, issn = {1471-2164}, support = {31003A-162548/1//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Animals ; Asthma/chemically induced/genetics/*veterinary ; Dust ; Gene Expression Profiling/*veterinary ; Gene Expression Regulation ; Gene Regulatory Networks/drug effects ; Genetic Predisposition to Disease ; Genome-Wide Association Study/veterinary ; Horse Diseases/chemically induced/*genetics ; Horses ; Leukocytes, Mononuclear/drug effects ; Lipopolysaccharides/adverse effects ; *Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: Severe equine asthma, also known as recurrent airway obstruction (RAO), is a debilitating, performance limiting, obstructive respiratory condition in horses that is phenotypically similar to human asthma. Past genome wide association studies (GWAS) have not discovered coding variants associated with RAO, leading to the hypothesis that causative variant(s) underlying the signals are likely non-coding, regulatory variant(s). Regions of the genome containing variants that influence the number of expressed RNA molecules are expression quantitative trait loci (eQTLs). Variation associated with RAO that also regulates a gene's expression in a disease relevant tissue could help identify candidate genes that influence RAO if that gene's expression is also associated with RAO disease status.

RESULTS: We searched for eQTLs by analyzing peripheral blood mononuclear cells (PBMCs) from two half-sib families and one unrelated cohort of 82 European Warmblood horses that were previously treated in vitro with: no stimulation (MCK), lipopolysaccharides (LPS), recombinant cyathostomin antigen (RCA), and hay-dust extract (HDE). We identified high confidence eQTLs that did not violate linear modeling assumptions and were not significant due to single outlier individuals. We identified a mean of 4347 high confidence eQTLs in four treatments of PBMCs, and discovered two trans regulatory hotspots regulating genes involved in related biological pathways. We corroborated previous RAO associated single nucleotide polymorphisms (SNPs), and increased the resolution of past GWAS by analyzing 1,056,195 SNPs in 361 individuals. We identified four RAO-associated SNPs that only regulate gene expression of dexamethasone-induced protein (DEXI), however we found no significant association between DEXI gene expression and presence of RAO.

CONCLUSIONS: Thousands of genetic variants regulate gene expression in PBMCs of European Warmblood horses in cis and trans. Most high confidence eSNPs are significantly enriched near the transcription start sites of their target genes. Two trans regulatory hotspots on chromosome 11 and 13 regulate many genes involved in transmembrane cell signaling and neurological development respectively when PBMCs are treated with HDE. None of the top fifteen RAO associated SNPs strongly influence disease status through gene expression regulation.}, } @article {pmid30071757, year = {2018}, author = {Wilson, S and Bassiou, E and Denli, A and Dolan, LC and Watson, M}, title = {Traveling Groups Stick Together: How Collective Directional Movement Influences Social Cohesion.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918792134}, doi = {10.1177/1474704918792134}, pmid = {30071757}, issn = {1474-7049}, mesh = {Analysis of Variance ; Female ; Friends ; *Group Processes ; Humans ; *Interpersonal Relations ; Male ; Sense of Coherence ; *Social Behavior ; Young Adult ; }, abstract = {We tested the hypothesis that the social act of moving through space with others-collective directional movement-is associated with greater levels of group cohesion compared to static activities. We asked participants to imagine participating in activities as part of a same-sex group and found that imagining going on a journey is associated with higher levels of expected cohesion compared to imagining attending a meeting (Study 1) or an event (Study 2). Study 3 replicates the main effect using different manipulations and finds that it persists regardless of whether the imagined group were friends or strangers. Two further studies employed real-world tasks and show that the effect is not a consequence of goal ascription (Study 4) or synchrony/exertion (Study 5). We argue that the link between this activity and cohesion is a consequence of its ubiquity in social ecologies and the interdependence and shared common fate of those engaged in it.}, } @article {pmid30071754, year = {2018}, author = {Gračanin, A and Krahmer, E and Rinck, M and Vingerhoets, AJJM}, title = {The Effects of Tears on Approach-Avoidance Tendencies in Observers.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918791058}, doi = {10.1177/1474704918791058}, pmid = {30071754}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Altruism ; Avoidance Learning/*physiology ; Crying/*psychology ; Facial Expression ; Female ; Humans ; Interpersonal Relations ; Male ; Photic Stimulation ; Psychological Tests ; Reaction Time ; Tears ; Young Adult ; }, abstract = {Emotional tears have been proposed to represent a robust affiliative signal whose main function is to promote the willingness to help the crying individual. However, little is known about the psychological mechanisms at the basis of such responses. To investigate whether tears facilitate approach relative to avoidance tendencies, we exposed participants (N = 77) to pictures of faces with and without visible tears, in two different approach-avoidance tasks. In the first task, participants were instructed to either move toward tearful faces and away from nontearful faces, or the other way around, by using a joystick. In the second task, participants made approaching or avoiding responses to tearful and nontearful faces by pressing buttons. The results suggest that tears facilitate behavior that reduces the distance between the observer and the crying person. However, while tears appear to promote approach relative to avoidance behavior, the current findings do not allow firm conclusions about whether tears specifically facilitate approach or rather block avoidance tendencies in observers, or whether they possibly have both effects. Findings are discussed in the context of tears' ability to act as a prosocial stimulus that signals non-aggressive intentions, as well as in the context of the functional goals that predispose humans to approach or avoid crying individuals.}, } @article {pmid30071527, year = {2018}, author = {Neuhauser, S and Handler, J and Schelling, C and Pieńkowska-Schelling, A}, title = {Disorder of Sexual Development in a Mare with an Unusual Tentative Mosaic Karyotype: 63,X/64,Xdel(Y).}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000490861}, pmid = {30071527}, issn = {1661-5433}, abstract = {The present report describes a 4-year-old Trakehner mare which was referred to the clinic for a breeding soundness evaluation. Clinical, histological, and postmortem examination revealed an underdeveloped genital tract, the absence of a cervix uteri, and small inactive ovaries without male gonadal tissue. Blood lymphocyte analysis revealed an unusual mosaic karyotype consisting of 2 cell lines. For the majority of cells (70%), monosomy X (63,X) was observed. The remaining cells (30%) contained 64 chromosomes including one X chromosome and a small rudimentary Y chromosome consisting mostly of heterochromatin. The centromere was retained, but its full functionality was questionable. PCR analysis revealed that the entire male-specific region of Y (Yq14), including the SRY gene, was deleted. It remained unclear if the pseudoautosomal region (Yq15) and parts of the heterochromatic region (Yq13) were affected by this deletion. The phenotype of the mare with this disorder of sex development associated with sex chromosome abnormalities is genetically comparable to 63,X monosomy which fully explains the clinical findings.}, } @article {pmid30071218, year = {2018}, author = {Della Gaspera, B and Chesneau, A and Weill, L and Charbonnier, F and Chanoine, C}, title = {Xenopus SOX5 enhances myogenic transcription indirectly through transrepression.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {262-275}, doi = {10.1016/j.ydbio.2018.07.025}, pmid = {30071218}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation/physiology ; Homeodomain Proteins/genetics/metabolism ; Mesoderm/metabolism ; Muscle Cells/metabolism ; Muscle Development/genetics ; Muscles/metabolism ; MyoD Protein/genetics/metabolism ; SOXD Transcription Factors/genetics/*metabolism ; Somites/metabolism ; Transcriptional Activation/physiology ; Xenopus Proteins/genetics/*metabolism ; Xenopus laevis ; }, abstract = {In anamniotes, somite compartimentalization in the lateral somitic domain leads simultaneously to myotome and dermomyotome formation. In the myotome, Xenopus Sox5 is co-expressed with Myod1 in the course of myogenic differentiation. Here, we studied the function of Sox5 using a Myod1-induced myogenic transcription assay in pluripotent cells of animal caps. We found that Sox5 enhances myogenic transcription of muscle markers Des, Actc1, Ckm and MyhE3. The use of chimeric transactivating or transrepressive Sox5 proteins indicates that Sox5 acts as a transrepressor and indirectly stimulates myogenic transcription except for the slow muscle-specific genes Myh7L, Myh7S, Myl2 and Tnnc1. We showed that this role is shared by Sox6, which is structurally similar to Sox5, both belonging to the SoxD subfamily of transcription factors. Moreover, Sox5 can antagonize the inhibitory function of Meox2 on myogenic differentiation. Meox2 which is a dermomyotome marker, represses myogenic transcription in Myod-induced myogenic transcription assay and in Nodal5-induced mesoderm from animal cap assay. The inhibitory function of Meox2 and the pro-myogenic function of Sox5 were confirmed during Xenopus normal development by the use of translation-blocking oligomorpholinos and dexamethasone inducible chimeric Sox5 and Meox2 proteins. We have therefore identified a new function for SoxD proteins in muscle cells, which can indirectly enhance myogenic transcription through transrepression, in addition to the previously identified function as a direct repressor of slow muscle-specific genes.}, } @article {pmid30071217, year = {2018}, author = {Rothstein, M and Bhattacharya, D and Simoes-Costa, M}, title = {The molecular basis of neural crest axial identity.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.07.026}, pmid = {30071217}, issn = {1095-564X}, support = {R00 DE024232/DE/NIDCR NIH HHS/United States ; }, abstract = {The neural crest is a migratory cell population that contributes to multiple tissues and organs during vertebrate embryonic development. It is remarkable in its ability to differentiate into an array of different cell types, including melanocytes, cartilage, bone, smooth muscle, and peripheral nerves. Although neural crest cells are formed along the entire anterior-posterior axis of the developing embryo, they can be divided into distinct subpopulations based on their axial level of origin. These groups of cells, which include the cranial, vagal, trunk, and sacral neural crest, display varied migratory patterns and contribute to multiple derivatives. While these subpopulations have been shown to be mostly plastic and to differentiate according to environmental cues, differences in their intrinsic potentials have also been identified. For instance, the cranial neural crest is unique in its ability to give rise to cartilage and bone. Here, we examine the molecular features that underlie such developmental restrictions and discuss the hypothesis that distinct gene regulatory networks operate in these subpopulations. We also consider how reconstructing the phylogeny of the trunk and cranial neural crest cells impacts our understanding of vertebrate evolution.}, } @article {pmid30071216, year = {2018}, author = {Ménard, M and Costechareyre, C and Coelho-Aguiar, JM and Jarrosson-Wuilleme, L and Rama, N and Blachier, J and Kindbeiter, K and Bozon, M and Cabrera, JR and Dupin, E and Le Douarin, N and Mehlen, P and Tauszig-Delamasure, S}, title = {The dependence receptor TrkC regulates the number of sensory neurons during DRG development.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {249-261}, doi = {10.1016/j.ydbio.2018.07.022}, pmid = {30071216}, issn = {1095-564X}, mesh = {Animals ; Apoptosis/physiology ; Cell Line ; Cell Survival/physiology ; Chick Embryo ; Female ; Ganglia, Spinal/*cytology/embryology/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Growth Factors/genetics/metabolism ; Receptor, trkC/*metabolism ; Sensory Receptor Cells/*cytology/*metabolism ; }, abstract = {The development of the sensory nervous system is the result of fine-tuned waves of neurogenesis and apoptosis which control the appropriate number of precursors and newly generated neurons and orient them toward a specific lineage. Neurotrophins and their tyrosine-kinase receptors (RTK) orchestrate this process. They have long been in the scope of the neurotrophic theory which established that a neuron is committed to die unless a trophic factor generated by its target provides it with a survival signal. The neural death has thus always been described as a "default" program, survival being the major player to control the number of cells. New insights have been brought by the gain of function studies which recently demonstrated that TrkC (NTRK3) is a "dependence receptor" able to actively trigger apoptosis in absence of its ligand NT-3. In order to address the role of TrkC pro-apoptotic activity in the control of sensory neurons number, we generated a TrkC gene-trap mutant mice. We found out that this new murine model recapitulates the sensory phenotype of TrkC constitutive mutants, with reduced DRG size and reduced number of DRG neurons. We engineered these mice strain with a lacZ reporter in order to follow the fate of neurons committed to a TrkC lineage and observed that they are specifically protected from NT-3 mediated apoptosis in NT-3/TrkC double knock-out embryos. Finally, using a chicken model we demonstrated that silencing NT-3 emanating from the ventral neural tube induced apoptosis in the DRG anlage. This apoptosis was inhibited by silencing TrkC. This work thus demonstrates that, during in vivo DRG development, TrkC behaves as a two-sided receptor transducing positive signals of neuronal survival in response to NT-3, but actively inducing neuronal cell death when unbound. This functional duality sets adequate number of neurons committed to a TrkC identity in the forming DRG.}, } @article {pmid30070622, year = {2018}, author = {Fotedar, R and Kolecka, A and Boekhout, T and Fell, JW and Anand, A and Al Malaki, A and Zeyara, A and Al Marri, M}, title = {Naganishia qatarensis sp. nov., a novel basidiomycetous yeast species from a hypersaline marine environment in Qatar.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2924-2929}, doi = {10.1099/ijsem.0.002920}, pmid = {30070622}, issn = {1466-5034}, mesh = {Basidiomycota/*classification/genetics/isolation & purification ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Mycological Typing Techniques ; *Phylogeny ; Qatar ; Salinity ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {Two yeast strains (INY29 and INY13) representing a novel yeast species were isolated from the hypersaline marine environment of the Inland Sea, Qatar. Phylogenetic analysis based on the D1/D2 domains of the large subunit (LSU) regions and internal transcribed spacer (ITS1 and ITS2) regions showed that the two strains represent a single species in the genus Naganishia that is distinct from other species. These two strains were classified as members of the genus Naganishia and clustered in a strongly supported clade represented by Naganishia albidus in the Filobasidiales order in the phylogenetic tree drawn from ITS and D1/D2 sequences. The novel species was most closely related to the type strain of Naganishia cerealis but the two species differed by 1 % sequence divergence (four substitutions and one gap) in the D1/D2 domains and (five substitutions and one gap) in the ITS regions. In contrast to the closest relative, N. cerealis, the novel yeast species assimilated melibiose, glycerol, meso-erythritol, dl-lactate, methanol, propane 1-2-diol, butane 2-3-diol, and grew at 35 °C. The name Naganishia qatarensis sp. nov. is proposed to accommodate these strains, with INY29 as the holotype.}, } @article {pmid30069060, year = {2018}, author = {Cloney, R}, title = {Dynamic RNAs in sperm shape embryo development.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {591}, doi = {10.1038/s41576-018-0042-x}, pmid = {30069060}, issn = {1471-0064}, } @article {pmid30069054, year = {2018}, author = {Halperin, SO and Tou, CJ and Wong, EB and Modavi, C and Schaffer, DV and Dueber, JE}, title = {CRISPR-guided DNA polymerases enable diversification of all nucleotides in a tunable window.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {248-252}, doi = {10.1038/s41586-018-0384-8}, pmid = {30069054}, issn = {1476-4687}, abstract = {The capacity to diversify genetic codes advances our ability to understand and engineer biological systems1,2. A method for continuously diversifying user-defined regions of a genome would enable forward genetic approaches in systems that are not amenable to efficient homology-directed oligonucleotide integration. It would also facilitate the rapid evolution of biotechnologically useful phenotypes through accelerated and parallelized rounds of mutagenesis and selection, as well as cell-lineage tracking through barcode mutagenesis. Here we present EvolvR, a system that can continuously diversify all nucleotides within a tunable window length at user-defined loci. This is achieved by directly generating mutations using engineered DNA polymerases targeted to loci via CRISPR-guided nickases. We identified nickase and polymerase variants that offer a range of targeted mutation rates that are up to 7,770,000-fold greater than rates seen in wild-type cells, and editing windows with lengths of up to 350 nucleotides. We used EvolvR to identify novel ribosomal mutations that confer resistance to the antibiotic spectinomycin. Our results demonstrate that CRISPR-guided DNA polymerases enable multiplexed and continuous diversification of user-defined genomic loci, which will be useful for a broad range of basic and biotechnological applications.}, } @article {pmid30069053, year = {2018}, author = {Lee, JH and Lee, JE and Kahng, JY and Kim, SH and Park, JS and Yoon, SJ and Um, JY and Kim, WK and Lee, JK and Park, J and Kim, EH and Lee, JH and Lee, JH and Chung, WS and Ju, YS and Park, SH and Chang, JH and Kang, SG and Lee, JH}, title = {Human glioblastoma arises from subventricular zone cells with low-level driver mutations.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {243-247}, doi = {10.1038/s41586-018-0389-3}, pmid = {30069053}, issn = {1476-4687}, abstract = {Glioblastoma (GBM) is a devastating and incurable brain tumour, with a median overall survival of fifteen months1,2. Identifying the cell of origin that harbours mutations that drive GBM could provide a fundamental basis for understanding disease progression and developing new treatments. Given that the accumulation of somatic mutations has been implicated in gliomagenesis, studies have suggested that neural stem cells (NSCs), with their self-renewal and proliferative capacities, in the subventricular zone (SVZ) of the adult human brain may be the cells from which GBM originates3-5. However, there is a lack of direct genetic evidence from human patients with GBM4,6-10. Here we describe direct molecular genetic evidence from patient brain tissue and genome-edited mouse models that show astrocyte-like NSCs in the SVZ to be the cell of origin that contains the driver mutations of human GBM. First, we performed deep sequencing of triple-matched tissues, consisting of (i) normal SVZ tissue away from the tumour mass, (ii) tumour tissue, and (iii) normal cortical tissue (or blood), from 28 patients with isocitrate dehydrogenase (IDH) wild-type GBM or other types of brain tumour. We found that normal SVZ tissue away from the tumour in 56.3% of patients with wild-type IDH GBM contained low-level GBM driver mutations (down to approximately 1% of the mutational burden) that were observed at high levels in their matching tumours. Moreover, by single-cell sequencing and laser microdissection analysis of patient brain tissue and genome editing of a mouse model, we found that astrocyte-like NSCs that carry driver mutations migrate from the SVZ and lead to the development of high-grade malignant gliomas in distant brain regions. Together, our results show that NSCs in human SVZ tissue are the cells of origin that contain the driver mutations of GBM.}, } @article {pmid30069052, year = {2018}, author = {Horie, R and Hazbun, A and Chen, K and Cao, C and Levine, M and Horie, T}, title = {Shared evolutionary origin of vertebrate neural crest and cranial placodes.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {228-232}, doi = {10.1038/s41586-018-0385-7}, pmid = {30069052}, issn = {1476-4687}, support = {R01 NS076542/NS/NINDS NIH HHS/United States ; }, abstract = {Placodes and neural crests represent defining features of vertebrates, yet their relationship remains unclear despite extensive investigation1-3. Here we use a combination of lineage tracing, gene disruption and single-cell RNA-sequencing assays to explore the properties of the lateral plate ectoderm of the proto-vertebrate, Ciona intestinalis. There are notable parallels between the patterning of the lateral plate in Ciona and the compartmentalization of the neural plate ectoderm in vertebrates4. Both systems exhibit sequential patterns of Six1/2, Pax3/7 and Msxb expression that depend on a network of interlocking regulatory interactions4. In Ciona, this compartmentalization network produces distinct but related types of sensory cells that share similarities with derivatives of both cranial placodes and the neural crest in vertebrates. Simple genetic disruptions result in the conversion of one sensory cell type into another. We focused on bipolar tail neurons, because they arise from the tail regions of the lateral plate and possess properties of the dorsal root ganglia, a derivative of the neural crest in vertebrates5. Notably, bipolar tail neurons were readily transformed into palp sensory cells, a proto-placodal sensory cell type that arises from the anterior-most regions of the lateral plate in the Ciona tadpole6. Proof of transformation was confirmed by whole-embryo single-cell RNA-sequencing assays. These findings suggest that compartmentalization of the lateral plate ectoderm preceded the advent of vertebrates, and served as a common source for the evolution of both cranial placodes and neural crest3,4.}, } @article {pmid30069051, year = {2018}, author = {Bahram, M and Hildebrand, F and Forslund, SK and Anderson, JL and Soudzilovskaia, NA and Bodegom, PM and Bengtsson-Palme, J and Anslan, S and Coelho, LP and Harend, H and Huerta-Cepas, J and Medema, MH and Maltz, MR and Mundra, S and Olsson, PA and Pent, M and Põlme, S and Sunagawa, S and Ryberg, M and Tedersoo, L and Bork, P}, title = {Structure and function of the global topsoil microbiome.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {233-237}, doi = {10.1038/s41586-018-0386-6}, pmid = {30069051}, issn = {1476-4687}, abstract = {Soils harbour some of the most diverse microbiomes on Earth and are essential for both nutrient cycling and carbon storage. To understand soil functioning, it is necessary to model the global distribution patterns and functional gene repertoires of soil microorganisms, as well as the biotic and environmental associations between the diversity and structure of both bacterial and fungal soil communities1-4. Here we show, by leveraging metagenomics and metabarcoding of global topsoil samples (189 sites, 7,560 subsamples), that bacterial, but not fungal, genetic diversity is highest in temperate habitats and that microbial gene composition varies more strongly with environmental variables than with geographic distance. We demonstrate that fungi and bacteria show global niche differentiation that is associated with contrasting diversity responses to precipitation and soil pH. Furthermore, we provide evidence for strong bacterial-fungal antagonism, inferred from antibiotic-resistance genes, in topsoil and ocean habitats, indicating the substantial role of biotic interactions in shaping microbial communities. Our results suggest that both competition and environmental filtering affect the abundance, composition and encoded gene functions of bacterial and fungal communities, indicating that the relative contributions of these microorganisms to global nutrient cycling varies spatially.}, } @article {pmid30069050, year = {2018}, author = {Dick, RA and Zadrozny, KK and Xu, C and Schur, FKM and Lyddon, TD and Ricana, CL and Wagner, JM and Perilla, JR and Ganser-Pornillos, BK and Johnson, MC and Pornillos, O and Vogt, VM}, title = {Inositol phosphates are assembly co-factors for HIV-1.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {509-512}, pmid = {30069050}, issn = {1476-4687}, support = {R01 GM107013/GM/NIGMS NIH HHS/United States ; R01 GM105684/GM/NIGMS NIH HHS/United States ; P50 GM082251/GM/NIGMS NIH HHS/United States ; U54 GM103297/GM/NIGMS NIH HHS/United States ; P30 GM110758/GM/NIGMS NIH HHS/United States ; F32 GM115007/GM/NIGMS NIH HHS/United States ; R01 AI129678/AI/NIAID NIH HHS/United States ; R01 GM116961/GM/NIGMS NIH HHS/United States ; R01 GM110776/GM/NIGMS NIH HHS/United States ; }, abstract = {A short, 14-amino-acid segment called SP1, located in the Gag structural protein1, has a critical role during the formation of the HIV-1 virus particle. During virus assembly, the SP1 peptide and seven preceding residues fold into a six-helix bundle, which holds together the Gag hexamer and facilitates the formation of a curved immature hexagonal lattice underneath the viral membrane2,3. Upon completion of assembly and budding, proteolytic cleavage of Gag leads to virus maturation, in which the immature lattice is broken down; the liberated CA domain of Gag then re-assembles into the mature conical capsid that encloses the viral genome and associated enzymes. Folding and proteolysis of the six-helix bundle are crucial rate-limiting steps of both Gag assembly and disassembly, and the six-helix bundle is an established target of HIV-1 inhibitors4,5. Here, using a combination of structural and functional analyses, we show that inositol hexakisphosphate (InsP6, also known as IP6) facilitates the formation of the six-helix bundle and assembly of the immature HIV-1 Gag lattice. IP6 makes ionic contacts with two rings of lysine residues at the centre of the Gag hexamer. Proteolytic cleavage then unmasks an alternative binding site, where IP6 interaction promotes the assembly of the mature capsid lattice. These studies identify IP6 as a naturally occurring small molecule that promotes both assembly and maturation of HIV-1.}, } @article {pmid30069049, year = {2018}, author = {Baell, JB and Leaver, DJ and Hermans, SJ and Kelly, GL and Brennan, MS and Downer, NL and Nguyen, N and Wichmann, J and McRae, HM and Yang, Y and Cleary, B and Lagiakos, HR and Mieruszynski, S and Pacini, G and Vanyai, HK and Bergamasco, MI and May, RE and Davey, BK and Morgan, KJ and Sealey, AJ and Wang, B and Zamudio, N and Wilcox, S and Garnham, AL and Sheikh, BN and Aubrey, BJ and Doggett, K and Chung, MC and de Silva, M and Bentley, J and Pilling, P and Hattarki, M and Dolezal, O and Dennis, ML and Falk, H and Ren, B and Charman, SA and White, KL and Rautela, J and Newbold, A and Hawkins, ED and Johnstone, RW and Huntington, ND and Peat, TS and Heath, JK and Strasser, A and Parker, MW and Smyth, GK and Street, IP and Monahan, BJ and Voss, AK and Thomas, T}, title = {Inhibitors of histone acetyltransferases KAT6A/B induce senescence and arrest tumour growth.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {253-257}, doi = {10.1038/s41586-018-0387-5}, pmid = {30069049}, issn = {1476-4687}, abstract = {Acetylation of histones by lysine acetyltransferases (KATs) is essential for chromatin organization and function1. Among the genes coding for the MYST family of KATs (KAT5-KAT8) are the oncogenes KAT6A (also known as MOZ) and KAT6B (also known as MORF and QKF)2,3. KAT6A has essential roles in normal haematopoietic stem cells4-6 and is the target of recurrent chromosomal translocations, causing acute myeloid leukaemia7,8. Similarly, chromosomal translocations in KAT6B have been identified in diverse cancers8. KAT6A suppresses cellular senescence through the regulation of suppressors of the CDKN2A locus9,10, a function that requires its KAT activity10. Loss of one allele of KAT6A extends the median survival of mice with MYC-induced lymphoma from 105 to 413 days11. These findings suggest that inhibition of KAT6A and KAT6B may provide a therapeutic benefit in cancer. Here we present highly potent, selective inhibitors of KAT6A and KAT6B, denoted WM-8014 and WM-1119. Biochemical and structural studies demonstrate that these compounds are reversible competitors of acetyl coenzyme A and inhibit MYST-catalysed histone acetylation. WM-8014 and WM-1119 induce cell cycle exit and cellular senescence without causing DNA damage. Senescence is INK4A/ARF-dependent and is accompanied by changes in gene expression that are typical of loss of KAT6A function. WM-8014 potentiates oncogene-induced senescence in vitro and in a zebrafish model of hepatocellular carcinoma. WM-1119, which has increased bioavailability, arrests the progression of lymphoma in mice. We anticipate that this class of inhibitors will help to accelerate the development of therapeutics that target gene transcription regulated by histone acetylation.}, } @article {pmid30069048, year = {2018}, author = {Kong, L and Sochacki, KA and Wang, H and Fang, S and Canagarajah, B and Kehr, AD and Rice, WJ and Strub, MP and Taraska, JW and Hinshaw, JE}, title = {Cryo-EM of the dynamin polymer assembled on lipid membrane.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {258-262}, pmid = {30069048}, issn = {1476-4687}, support = {P41 GM103310/GM/NIGMS NIH HHS/United States ; S10 OD019994/OD/NIH HHS/United States ; Z01 DK060100-12/NULL/Intramural NIH HHS/United States ; Z01 DK060100-13/NULL/Intramural NIH HHS/United States ; }, abstract = {Membrane fission is a fundamental process in the regulation and remodelling of cell membranes. Dynamin, a large GTPase, mediates membrane fission by assembling around, constricting and cleaving the necks of budding vesicles1. Here we report a 3.75 Å resolution cryo-electron microscopy structure of the membrane-associated helical polymer of human dynamin-1 in the GMPPCP-bound state. The structure defines the helical symmetry of the dynamin polymer and the positions of its oligomeric interfaces, which were validated by cell-based endocytosis assays. Compared to the lipid-free tetramer form2, membrane-associated dynamin binds to the lipid bilayer with its pleckstrin homology domain (PHD) and self-assembles across the helical rungs via its guanine nucleotide-binding (GTPase) domain3. Notably, interaction with the membrane and helical assembly are accommodated by a severely bent bundle signalling element (BSE), which connects the GTPase domain to the rest of the protein. The BSE conformation is asymmetric across the inter-rung GTPase interface, and is unique compared to all known nucleotide-bound states of dynamin. The structure suggests that the BSE bends as a result of forces generated from the GTPase dimer interaction that are transferred across the stalk to the PHD and lipid membrane. Mutations that disrupted the BSE kink impaired endocytosis. We also report a 10.1 Å resolution cryo-electron microscopy map of a super-constricted dynamin polymer showing localized conformational changes at the BSE and GTPase domains, induced by GTP hydrolysis, that drive membrane constriction. Together, our results provide a structural basis for the mechanism of action of dynamin on the lipid membrane.}, } @article {pmid30069047, year = {2018}, author = {Luo, J and Sun, X and Cormack, BP and Boeke, JD}, title = {Karyotype engineering by chromosome fusion leads to reproductive isolation in yeast.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {392-396}, doi = {10.1038/s41586-018-0374-x}, pmid = {30069047}, issn = {1476-4687}, support = {MCB-1616111//National Science Foundation/International ; }, abstract = {Extant species have wildly different numbers of chromosomes, even among taxa with relatively similar genome sizes (for example, insects)1,2. This is likely to reflect accidents of genome history, such as telomere-telomere fusions and genome duplication events3-5. Humans have 23 pairs of chromosomes, whereas other apes have 24. One human chromosome is a fusion product of the ancestral state6. This raises the question: how well can species tolerate a change in chromosome numbers without substantial changes to genome content? Many tools are used in chromosome engineering in Saccharomyces cerevisiae7-10, but CRISPR-Cas9-mediated genome editing facilitates the most aggressive engineering strategies. Here we successfully fused yeast chromosomes using CRISPR-Cas9, generating a near-isogenic series of strains with progressively fewer chromosomes ranging from sixteen to two. A strain carrying only two chromosomes of about six megabases each exhibited modest transcriptomic changes and grew without major defects. When we crossed a sixteen-chromosome strain with strains with fewer chromosomes, we noted two trends. As the number of chromosomes dropped below sixteen, spore viability decreased markedly, reaching less than 10% for twelve chromosomes. As the number of chromosomes decreased further, yeast sporulation was arrested: a cross between a sixteen-chromosome strain and an eight-chromosome strain showed greatly reduced full tetrad formation and less than 1% sporulation, from which no viable spores could be recovered. However, homotypic crosses between pairs of strains with eight, four or two chromosomes produced excellent sporulation and spore viability. These results indicate that eight chromosome-chromosome fusion events suffice to isolate strains reproductively. Overall, budding yeast tolerates a reduction in chromosome number unexpectedly well, providing a striking example of the robustness of genomes to change.}, } @article {pmid30069046, year = {2018}, author = {Plasschaert, LW and Žilionis, R and Choo-Wing, R and Savova, V and Knehr, J and Roma, G and Klein, AM and Jaffe, AB}, title = {A single-cell atlas of the airway epithelium reveals the CFTR-rich pulmonary ionocyte.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {377-381}, pmid = {30069046}, issn = {1476-4687}, support = {R01 HL141402/HL/NHLBI NIH HHS/United States ; R33 CA212697/CA/NCI NIH HHS/United States ; }, abstract = {The functions of epithelial tissues are dictated by the types, abundance and distribution of the differentiated cells they contain. Attempts to restore tissue function after damage require knowledge of how physiological tasks are distributed among cell types, and how cell states vary between homeostasis, injury-repair and disease. In the conducting airway, a heterogeneous basal cell population gives rise to specialized luminal cells that perform mucociliary clearance1. Here we perform single-cell profiling of human bronchial epithelial cells and mouse tracheal epithelial cells to obtain a comprehensive census of cell types in the conducting airway and their behaviour in homeostasis and regeneration. Our analysis reveals cell states that represent known and novel cell populations, delineates their heterogeneity and identifies distinct differentiation trajectories during homeostasis and tissue repair. Finally, we identified a novel, rare cell type that we call the 'pulmonary ionocyte', which co-expresses FOXI1, multiple subunits of the vacuolar-type H+-ATPase (V-ATPase) and CFTR, the gene that is mutated in cystic fibrosis. Using immunofluorescence, modulation of signalling pathways and electrophysiology, we show that Notch signalling is necessary and FOXI1 expression is sufficient to drive the production of the pulmonary ionocyte, and that the pulmonary ionocyte is a major source of CFTR activity in the conducting airway epithelium.}, } @article {pmid30069045, year = {2018}, author = {Shao, Y and Lu, N and Wu, Z and Cai, C and Wang, S and Zhang, LL and Zhou, F and Xiao, S and Liu, L and Zeng, X and Zheng, H and Yang, C and Zhao, Z and Zhao, G and Zhou, JQ and Xue, X and Qin, Z}, title = {Creating a functional single-chromosome yeast.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {331-335}, doi = {10.1038/s41586-018-0382-x}, pmid = {30069045}, issn = {1476-4687}, abstract = {Eukaryotic genomes are generally organized in multiple chromosomes. Here we have created a functional single-chromosome yeast from a Saccharomyces cerevisiae haploid cell containing sixteen linear chromosomes, by successive end-to-end chromosome fusions and centromere deletions. The fusion of sixteen native linear chromosomes into a single chromosome results in marked changes to the global three-dimensional structure of the chromosome due to the loss of all centromere-associated inter-chromosomal interactions, most telomere-associated inter-chromosomal interactions and 67.4% of intra-chromosomal interactions. However, the single-chromosome and wild-type yeast cells have nearly identical transcriptome and similar phenome profiles. The giant single chromosome can support cell life, although this strain shows reduced growth across environments, competitiveness, gamete production and viability. This synthetic biology study demonstrates an approach to exploration of eukaryote evolution with respect to chromosome structure and function.}, } @article {pmid30069044, year = {2018}, author = {Montoro, DT and Haber, AL and Biton, M and Vinarsky, V and Lin, B and Birket, SE and Yuan, F and Chen, S and Leung, HM and Villoria, J and Rogel, N and Burgin, G and Tsankov, AM and Waghray, A and Slyper, M and Waldman, J and Nguyen, L and Dionne, D and Rozenblatt-Rosen, O and Tata, PR and Mou, H and Shivaraju, M and Bihler, H and Mense, M and Tearney, GJ and Rowe, SM and Engelhardt, JF and Regev, A and Rajagopal, J}, title = {A revised airway epithelial hierarchy includes CFTR-expressing ionocytes.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {319-324}, pmid = {30069044}, issn = {1476-4687}, support = {P30 DK072482/DK/NIDDK NIH HHS/United States ; P01 HL051670/HL/NHLBI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; K99 HL127181/HL/NHLBI NIH HHS/United States ; R00 HL127181/HL/NHLBI NIH HHS/United States ; F31 HL136128/HL/NHLBI NIH HHS/United States ; R35 HL135816/HL/NHLBI NIH HHS/United States ; P30 DK054759/DK/NIDDK NIH HHS/United States ; R01 DK047967/DK/NIDDK NIH HHS/United States ; R24 HL123482/HL/NHLBI NIH HHS/United States ; }, abstract = {The airways of the lung are the primary sites of disease in asthma and cystic fibrosis. Here we study the cellular composition and hierarchy of the mouse tracheal epithelium by single-cell RNA-sequencing (scRNA-seq) and in vivo lineage tracing. We identify a rare cell type, the Foxi1+ pulmonary ionocyte; functional variations in club cells based on their location; a distinct cell type in high turnover squamous epithelial structures that we term 'hillocks'; and disease-relevant subsets of tuft and goblet cells. We developed 'pulse-seq', combining scRNA-seq and lineage tracing, to show that tuft, neuroendocrine and ionocyte cells are continually and directly replenished by basal progenitor cells. Ionocytes are the major source of transcripts of the cystic fibrosis transmembrane conductance regulator in both mouse (Cftr) and human (CFTR). Knockout of Foxi1 in mouse ionocytes causes loss of Cftr expression and disrupts airway fluid and mucus physiology, phenotypes that are characteristic of cystic fibrosis. By associating cell-type-specific expression programs with key disease genes, we establish a new cellular narrative for airways disease.}, } @article {pmid30069043, year = {2018}, author = {Lindgren, A and Hugelius, G and Kuhry, P}, title = {Extensive loss of past permafrost carbon but a net accumulation into present-day soils.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {219-222}, doi = {10.1038/s41586-018-0371-0}, pmid = {30069043}, issn = {1476-4687}, abstract = {Atmospheric concentrations of carbon dioxide increased between the Last Glacial Maximum (LGM, around 21,000 years ago) and the preindustrial era1. It is thought that the evolution of this atmospheric carbon dioxide (and that of atmospheric methane) during the glacial-to-interglacial transition was influenced by organic carbon that was stored in permafrost during the LGM and then underwent decomposition and release following thaw2,3. It has also been suggested that the rather erratic atmospheric δ13C and ∆14C signals seen during deglaciation1,4 could partly be explained by the presence of a large terrestrial inert LGM carbon stock, despite the biosphere being less productive (and therefore storing less carbon)5,6. Here we present an empirically derived estimate of the carbon stored in permafrost during the LGM by reconstructing the extent and carbon content of LGM biomes, peatland regions and deep sedimentary deposits. We find that the total estimated soil carbon stock for the LGM northern permafrost region is smaller than the estimated present-day storage (in both permafrost and non-permafrost soils) for the same region. A substantial decrease in the permafrost area from the LGM to the present day has been accompanied by a roughly 400-petagram increase in the total soil carbon stock. This increase in soil carbon suggests that permafrost carbon has made no net contribution to the atmospheric carbon pool since the LGM. However, our results also indicate potential postglacial reductions in the portion of the carbon stock that is trapped in permafrost, of around 1,000 petagrams, supporting earlier studies7. We further find that carbon has shifted from being primarily stored in permafrost mineral soils and loess deposits during the LGM, to being roughly equally divided between peatlands, mineral soils and permafrost loess deposits today.}, } @article {pmid30069042, year = {2018}, author = {Caves, EM and Green, PA and Zipple, MN and Peters, S and Johnsen, S and Nowicki, S}, title = {Categorical perception of colour signals in a songbird.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {365-367}, doi = {10.1038/s41586-018-0377-7}, pmid = {30069042}, issn = {1476-4687}, abstract = {In many contexts, animals assess each other using signals that vary continuously across individuals and, on average, reflect variation in the quality of the signaller1,2. It is often assumed that signal receivers perceive and respond continuously to continuous variation in the signal2. Alternatively, perception and response may be discontinuous3, owing to limitations in discrimination, categorization or both. Discrimination is the ability to tell two stimuli apart (for example, whether one can tell apart colours close to each other in hue). Categorization concerns whether stimuli are grouped based on similarities (for example, identifying colours with qualitative similarities in hue as similar even if they can be distinguished)4. Categorical perception is a mechanism by which perceptual systems categorize continuously varying stimuli, making specific predictions about discrimination relative to category boundaries. Here we show that female zebra finches (Taeniopygia guttata) categorically perceive a continuously variable assessment signal: the orange to red spectrum of male beak colour. Both predictions of categorical perception5 were supported: females (1) categorized colour stimuli that varied along a continuum and (2) showed increased discrimination between colours from opposite sides of a category boundary compared to equally different colours from within a category. To our knowledge, this is the first demonstration of categorical perception of signal-based colouration in a bird, with implications for understanding avian colour perception and signal evolution in general.}, } @article {pmid30069041, year = {2018}, author = {Raffel, S and Falcone, M and Kneisel, N and Hansson, J and Wang, W and Lutz, C and Bullinger, L and Poschet, G and Nonnenmacher, Y and Barnert, A and Bahr, C and Zeisberger, P and Przybylla, A and Sohn, M and Tönjes, M and Erez, A and Adler, L and Jensen, P and Scholl, C and Fröhling, S and Cocciardi, S and Wuchter, P and Thiede, C and Flörcken, A and Westermann, J and Ehninger, G and Lichter, P and Hiller, K and Hell, R and Herrmann, C and Ho, AD and Krijgsveld, J and Radlwimmer, B and Trumpp, A}, title = {Author Correction: BCAT1 restricts αKG levels in AML stem cells leading to IDHmut-like DNA hypermethylation.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {E28}, doi = {10.1038/s41586-018-0403-9}, pmid = {30069041}, issn = {1476-4687}, abstract = {In Extended Data Fig. 1a of this Letter, the flow cytometry plot depicting the surface phenotype of AML sample DD08 was a duplicate of the plot for AML sample DD06. Supplementary Data 4 has been added to the Supplementary Information of the original Letter to clarify the proteome data acquisition and presentation. The original Letter has been corrected online.}, } @article {pmid30068960, year = {2018}, author = {}, title = {Volcano threat, Parkinson's trial and harassment lawsuits.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {10-11}, doi = {10.1038/d41586-018-05841-3}, pmid = {30068960}, issn = {1476-4687}, } @article {pmid30068959, year = {2018}, author = {Al-Matrouk, F}, title = {The tail of Danny Whiskers.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {136}, doi = {10.1038/d41586-018-05767-w}, pmid = {30068959}, issn = {1476-4687}, } @article {pmid30068958, year = {2018}, author = {Zhang, B}, title = {Reflection forbidden and refraction reversed in an artificial crystal.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {37-38}, doi = {10.1038/d41586-018-05806-6}, pmid = {30068958}, issn = {1476-4687}, mesh = {*Electrons ; *Physics ; Sound ; }, } @article {pmid30068957, year = {2018}, author = {Ogle, K}, title = {Hyperactive soil microbes might weaken the terrestrial carbon sink.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {32-33}, doi = {10.1038/d41586-018-05842-2}, pmid = {30068957}, issn = {1476-4687}, } @article {pmid30068956, year = {2018}, author = {}, title = {How lizards got their big feet.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {5}, doi = {10.1038/d41586-018-05821-7}, pmid = {30068956}, issn = {1476-4687}, mesh = {Animals ; *Cyclonic Storms ; Female ; Foot/*anatomy & histology/*physiology ; Lizards/*anatomy & histology/genetics/*physiology ; Male ; Organ Size/genetics/physiology ; *Selection, Genetic/genetics ; West Indies ; }, } @article {pmid30068955, year = {2018}, author = {Radovic, A and Williams, M and Rousseau, D and Kagan, M and Bonacorsi, D and Himmel, A and Aurisano, A and Terao, K and Wongjirad, T}, title = {Machine learning at the energy and intensity frontiers of particle physics.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {41-48}, doi = {10.1038/s41586-018-0361-2}, pmid = {30068955}, issn = {1476-4687}, abstract = {Our knowledge of the fundamental particles of nature and their interactions is summarized by the standard model of particle physics. Advancing our understanding in this field has required experiments that operate at ever higher energies and intensities, which produce extremely large and information-rich data samples. The use of machine-learning techniques is revolutionizing how we interpret these data samples, greatly increasing the discovery potential of present and future experiments. Here we summarize the challenges and opportunities that come with the use of machine learning at the frontiers of particle physics.}, } @article {pmid30068954, year = {2018}, author = {He, H and Qiu, C and Ye, L and Cai, X and Fan, X and Ke, M and Zhang, F and Liu, Z}, title = {Topological negative refraction of surface acoustic waves in a Weyl phononic crystal.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {61-64}, doi = {10.1038/s41586-018-0367-9}, pmid = {30068954}, issn = {1476-4687}, abstract = {Reflection and refraction of waves occur at the interface between two different media. These two fundamental interfacial wave phenomena form the basis of fabricating various wave components, such as optical lenses. Classical refraction-now referred to as positive refraction-causes the transmitted wave to appear on the opposite side of the interface normal compared to the incident wave. By contrast, negative refraction results in the transmitted wave emerging on the same side of the interface normal. It has been observed in artificial materials1-5, following its theoretical prediction6, and has stimulated many applications including super-resolution imaging7. In general, reflection is inevitable during the refraction process, but this is often undesirable in designing wave functional devices. Here we report negative refraction of topological surface waves hosted by a Weyl phononic crystal-an acoustic analogue of the recently discovered Weyl semimetals8-12. The interfaces at which this topological negative refraction occurs are one-dimensional edges separating different facets of the crystal. By tailoring the surface terminations of the Weyl phononic crystal, constant-frequency contours of surface acoustic waves can be designed to produce negative refraction at certain interfaces, while positive refraction is realized at different interfaces within the same sample. In contrast to the more familiar behaviour of waves at interfaces, unwanted reflection can be prevented in our crystal, owing to the open nature of the constant-frequency contours, which is a hallmark of the topologically protected surface states in Weyl crystals8-12.}, } @article {pmid30068953, year = {2018}, author = {Perry, IB and Brewer, TF and Sarver, PJ and Schultz, DM and DiRocco, DA and MacMillan, DWC}, title = {Direct arylation of strong aliphatic C-H bonds.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {70-75}, pmid = {30068953}, issn = {1476-4687}, support = {R01 GM103558/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Products/chemical synthesis/chemistry ; Carbon/*chemistry ; Catalysis ; *Hydrogen Bonding ; Nickel/chemistry ; Tungsten Compounds/chemistry ; }, abstract = {Despite the widespread success of transition-metal-catalysed cross-coupling methodologies, considerable limitations still exist in reactions at sp3-hybridized carbon atoms, with most approaches relying on prefunctionalized alkylmetal or bromide coupling partners1,2. Although the use of native functional groups (for example, carboxylic acids, alkenes and alcohols) has improved the overall efficiency of such transformations by expanding the range of potential feedstocks3-5, the direct functionalization of carbon-hydrogen (C-H) bonds-the most abundant moiety in organic molecules-represents a more ideal approach to molecular construction. In recent years, an impressive range of reactions that form C(sp3)-heteroatom bonds from strong C-H bonds has been reported6,7. Additionally, valuable technologies have been developed for the formation of carbon-carbon bonds from the corresponding C(sp3)-H bonds via substrate-directed transition-metal C-H insertion8, undirected C-H insertion by captodative rhodium carbenoid complexes9, or hydrogen atom transfer from weak, hydridic C-H bonds by electrophilic open-shell species10-14. Despite these advances, a mild and general platform for the coupling of strong, neutral C(sp3)-H bonds with aryl electrophiles has not been realized. Here we describe a protocol for the direct C(sp3) arylation of a diverse set of aliphatic, C-H bond-containing organic frameworks through the combination of light-driven, polyoxometalate-facilitated hydrogen atom transfer and nickel catalysis. This dual-catalytic manifold enables the generation of carbon-centred radicals from strong, neutral C-H bonds, which thereafter act as nucleophiles in nickel-mediated cross-coupling with aryl bromides to afford C(sp3)-C(sp2) cross-coupled products. This technology enables unprecedented, single-step access to a broad array of complex, medicinally relevant molecules directly from natural products and chemical feedstocks through functionalization at sites that are unreactive under traditional methods.}, } @article {pmid30068952, year = {2018}, author = {Bond-Lamberty, B and Bailey, VL and Chen, M and Gough, CM and Vargas, R}, title = {Globally rising soil heterotrophic respiration over recent decades.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {80-83}, doi = {10.1038/s41586-018-0358-x}, pmid = {30068952}, issn = {1476-4687}, mesh = {Atmosphere/chemistry ; Carbon/analysis/metabolism ; Carbon Dioxide/analysis/metabolism ; *Cell Respiration ; Chlorophyll/metabolism ; Earth (Planet) ; *Ecosystem ; Fluorescence ; *Heterotrophic Processes ; Linear Models ; Meta-Analysis as Topic ; Plants/metabolism ; Soil/*chemistry ; Soil Microbiology ; Temperature ; }, abstract = {Global soils store at least twice as much carbon as Earth's atmosphere1,2. The global soil-to-atmosphere (or total soil respiration, RS) carbon dioxide (CO2) flux is increasing3,4, but the degree to which climate change will stimulate carbon losses from soils as a result of heterotrophic respiration (RH) remains highly uncertain5-8. Here we use an updated global soil respiration database9 to show that the observed soil surface RH:RS ratio increased significantly, from 0.54 to 0.63, between 1990 and 2014 (P = 0.009). Three additional lines of evidence provide support for this finding. By analysing two separate global gross primary production datasets10,11, we find that the ratios of both RH and RS to gross primary production have increased over time. Similarly, significant increases in RH are observed against the longest available solar-induced chlorophyll fluorescence global dataset, as well as gross primary production computed by an ensemble of global land models. We also show that the ratio of night-time net ecosystem exchange to gross primary production is rising across the FLUXNET201512 dataset. All trends are robust to sampling variability in ecosystem type, disturbance, methodology, CO2 fertilization effects and mean climate. Taken together, our findings provide observational evidence that global RH is rising, probably in response to environmental changes, consistent with meta-analyses13-16 and long-term experiments17. This suggests that climate-driven losses of soil carbon are currently occurring across many ecosystems, with a detectable and sustained trend emerging at the global scale.}, } @article {pmid30068951, year = {2018}, author = {Smith, EM and Shirey, SB and Richardson, SH and Nestola, F and Bullock, ES and Wang, J and Wang, W}, title = {Blue boron-bearing diamonds from Earth's lower mantle.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {84-87}, doi = {10.1038/s41586-018-0334-5}, pmid = {30068951}, issn = {1476-4687}, abstract = {Geological pathways for the recycling of Earth's surface materials into the mantle are both driven and obscured by plate tectonics1-3. Gauging the extent of this recycling is difficult because subducted crustal components are often released at relatively shallow depths, below arc volcanoes4-7. The conspicuous existence of blue boron-bearing diamonds (type IIb)8,9 reveals that boron, an element abundant in the continental and oceanic crust, is present in certain diamond-forming fluids at mantle depths. However, both the provenance of the boron and the geological setting of diamond crystallization were unknown. Here we show that boron-bearing diamonds carry previously unrecognized mineral assemblages whose high-pressure precursors were stable in metamorphosed oceanic lithospheric slabs at depths reaching the lower mantle. We propose that some of the boron in seawater-serpentinized oceanic lithosphere is subducted into the deep mantle, where it is released with hydrous fluids that enable diamond growth10. Type IIb diamonds are thus among the deepest diamonds ever found and indicate a viable pathway for the deep-mantle recycling of crustal elements.}, } @article {pmid30068609, year = {2018}, author = {Gebbie, MA and Ishiwata, H and McQuade, PJ and Petrak, V and Taylor, A and Freiwald, C and Dahl, JE and Carlson, RMK and Fokin, AA and Schreiner, PR and Shen, ZX and Nesladek, M and Melosh, NA}, title = {Experimental measurement of the diamond nucleation landscape reveals classical and nonclassical features.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8284-8289}, pmid = {30068609}, issn = {1091-6490}, abstract = {Nucleation is a core scientific concept that describes the formation of new phases and materials. While classical nucleation theory is applied across wide-ranging fields, nucleation energy landscapes have never been directly measured at the atomic level, and experiments suggest that nucleation rates often greatly exceed the predictions of classical nucleation theory. Multistep nucleation via metastable states could explain unexpectedly rapid nucleation in many contexts, yet experimental energy landscapes supporting such mechanisms are scarce, particularly at nanoscale dimensions. In this work, we measured the nucleation energy landscape of diamond during chemical vapor deposition, using a series of diamondoid molecules as atomically defined protonuclei. We find that 26-carbon atom clusters, which do not contain a single bulk atom, are postcritical nuclei and measure the nucleation barrier to be more than four orders of magnitude smaller than prior bulk estimations. These data support both classical and nonclassical concepts for multistep nucleation and growth during the gas-phase synthesis of diamond and other semiconductors. More broadly, these measurements provide experimental evidence that agrees with recent conceptual proposals of multistep nucleation pathways with metastable molecular precursors in diverse processes, ranging from cloud formation to protein crystallization, and nanoparticle synthesis.}, } @article {pmid30068608, year = {2018}, author = {Garriga, D and Headey, S and Accurso, C and Gunzburg, M and Scanlon, M and Coulibaly, F}, title = {Structural basis for the inhibition of poxvirus assembly by the antibiotic rifampicin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8424-8429}, pmid = {30068608}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/*pharmacology ; Capsid Proteins/*chemistry ; Magnetic Resonance Spectroscopy ; Poxviridae/*drug effects/physiology ; Protein Multimerization ; Rifampin/chemistry/*pharmacology ; Surface Plasmon Resonance ; Virus Assembly/*drug effects ; }, abstract = {Poxviruses are large DNA viruses that cause disease in animals and humans. They differ from classical enveloped viruses, because their membrane is acquired from cytoplasmic membrane precursors assembled onto a viral protein scaffold formed by the D13 protein rather than budding through cellular compartments. It was found three decades ago that the antibiotic rifampicin blocks this process and prevents scaffold formation. To elucidate the mechanism of action of rifampicin, we have determined the crystal structures of six D13-rifamycin complexes. These structures reveal that rifamycin compounds bind to a phenylalanine-rich region, or F-ring, at the membrane-proximal opening of the central channel of the D13 trimer. We show by NMR, surface plasmon resonance (SPR), and site-directed mutagenesis that A17, a membrane-associated viral protein, mediates the recruitment of the D13 scaffold by also binding to the F-ring. This interaction is the target of rifampicin, which prevents A17 binding, explaining the inhibition of viral morphogenesis. The F-ring of D13 is both conserved in sequence in mammalian poxviruses and essential for interaction with A17, defining a target for the development of assembly inhibitors. The model of the A17-D13 interaction describes a two-component system for remodeling nascent membranes that may be conserved in other large and giant DNA viruses.}, } @article {pmid30068607, year = {2018}, author = {Kodaimati, MS and Lian, S and Schatz, GC and Weiss, EA}, title = {Energy transfer-enhanced photocatalytic reduction of protons within quantum dot light-harvesting-catalyst assemblies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8290-8295}, pmid = {30068607}, issn = {1091-6490}, abstract = {Excitonic energy transfer (EnT) is the mechanism by which natural photosynthetic systems funnel energy from hundreds of antenna pigments to a single reaction center, which allows multielectron redox reactions to proceed with high efficiencies in low-flux natural light. This paper describes the use of electrostatically assembled CdSe quantum dot (QD) aggregates as artificial light harvesting-reaction center units for the photocatalytic reduction of H+ to H2, where excitons are funneled through EnT from sensitizer QDs (sQDs) to catalyst QDs (cQDs). Upon increasing the sensitizer-to-catalyst ratio in the aggregates from 1:2 to 20:1, the number of excitons delivered to each cQD (via EnT) per excitation of the system increases by a factor of nine. At the optimized sensitizer-to-catalyst ratio of 4:1, the internal quantum efficiency (IQE) of the reaction system is 4.0 ± 0.3%, a factor of 13 greater than the IQE of a sample that is identical except that EnT is suppressed due to the relative core sizes of the sQDs and cQDs. A kinetic model supports the proposed exciton funneling mechanism for enhancement of the catalytic activity.}, } @article {pmid30068606, year = {2018}, author = {Garrido-Gomez, T and Fisher, SJ and Simón, C}, title = {Reply to Liu et al.: Decidualization defect in severe preeclampsia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7656-E7657}, pmid = {30068606}, issn = {1091-6490}, mesh = {Decidua ; *Embryo Implantation ; Female ; Humans ; *Pre-Eclampsia ; Pregnancy ; }, } @article {pmid30068605, year = {2018}, author = {Post, RM}, title = {Myriad of implications of acetyl-l-carnitine deficits in depression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8475-8477}, pmid = {30068605}, issn = {1091-6490}, mesh = {*Acetylcarnitine ; Carnitine ; *Depression ; Depressive Disorder ; Humans ; }, } @article {pmid30068604, year = {2018}, author = {Bush, A and Döppler, JF and Goller, F and Mindlin, GB}, title = {Syringeal EMGs and synthetic stimuli reveal a switch-like activation of the songbird's vocal motor program.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8436-8441}, pmid = {30068604}, issn = {1091-6490}, support = {R01 DC006876/DC/NIDCD NIH HHS/United States ; R01 DC012859/DC/NIDCD NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Animals ; Electrocardiography ; *Electromyography ; Finches/*physiology ; Male ; Phonation ; Vocalization, Animal/*physiology ; }, abstract = {The coordination of complex vocal behaviors like human speech and oscine birdsong requires fine interactions between sensory and motor programs, the details of which are not completely understood. Here, we show that in sleeping male zebra finches (Taeniopygia guttata), the activity of the song system selectively evoked by playbacks of their own song can be detected in the syrinx. Electromyograms (EMGs) of a syringeal muscle show playback-evoked patterns strikingly similar to those recorded during song execution, with preferred activation instants within the song. Using this global and continuous readout, we studied the activation dynamics of the song system elicited by different auditory stimuli. We found that synthetic versions of the bird's song, rendered by a physical model of the avian phonation apparatus, evoked very similar responses, albeit with lower efficiency. Modifications of autogenous or synthetic songs reduce the response probability, but when present, the elicited activity patterns match execution patterns in shape and timing, indicating an all-or-nothing activation of the vocal motor program.}, } @article {pmid30068603, year = {2018}, author = {Yoshida, H and Tanimoto, E and Hirai, T and Miyanoiri, Y and Mitani, R and Kawamura, M and Takeda, M and Takehara, S and Hirano, K and Kainosho, M and Akagi, T and Matsuoka, M and Ueguchi-Tanaka, M}, title = {Evolution and diversification of the plant gibberellin receptor GID1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7844-E7853}, pmid = {30068603}, issn = {1091-6490}, mesh = {Adaptation, Physiological/*genetics ; Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; *Evolution, Molecular ; *Phylogeny ; Receptors, Cell Surface/*genetics/metabolism ; Species Specificity ; }, abstract = {The plant gibberellin (GA) receptor GID1 shows sequence similarity to carboxylesterase (CXE). Here, we report the molecular evolution of GID1 from establishment to functionally diverse forms in eudicots. By introducing 18 mutagenized rice GID1s into a rice gid1 null mutant, we identified the amino acids crucial for GID1 activity in planta. We focused on two amino acids facing the C2/C3 positions of ent-gibberellane, not shared by lycophytes and euphyllophytes, and found that adjustment of these residues resulted in increased GID1 affinity toward GA4, new acceptance of GA1 and GA3 carrying C13-OH as bioactive ligands, and elimination of inactive GAs. These residues rendered the GA perception system more sophisticated. We conducted phylogenetic analysis of 169 GID1s from 66 plant species and found that, unlike other taxa, nearly all eudicots contain two types of GID1, named A- and B-type. Certain B-type GID1s showed a unique evolutionary characteristic of significantly higher nonsynonymous-to-synonymous divergence in the region determining GA4 affinity. Furthermore, these B-type GID1s were preferentially expressed in the roots of Arabidopsis, soybean, and lettuce and might be involved in root elongation without shoot elongation for adaptive growth under low-temperature stress. Based on these observations, we discuss the establishment and adaption of GID1s during plant evolution.}, } @article {pmid30068602, year = {2018}, author = {Sznycer, D and Xygalatas, D and Alami, S and An, XF and Ananyeva, KI and Fukushima, S and Hitokoto, H and Kharitonov, AN and Koster, JM and Onyishi, CN and Onyishi, IE and Romero, PP and Takemura, K and Zhuang, JY and Cosmides, L and Tooby, J}, title = {Invariances in the architecture of pride across small-scale societies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8322-8327}, pmid = {30068602}, issn = {1091-6490}, mesh = {*Cognition ; Cross-Cultural Comparison ; *Emotions ; Humans ; *Social Behavior ; Societies ; }, abstract = {Becoming valuable to fellow group members so that one would attract assistance in times of need is a major adaptive problem. To solve it, the individual needs a predictive map of the degree to which others value different acts so that, in choosing how to act, the payoff arising from others' valuation of a potential action (e.g., showing bandmates that one is a skilled forager by pursuing a hard-to-acquire prey item) can be added to the direct payoff of the action (e.g., gaining the nutrients of the prey captured). The pride system seems to incorporate all of the elements necessary to solve this adaptive problem. Importantly, data from western(-ized), educated, industrialized, rich, and democratic (WEIRD) societies indicate close quantitative correspondences between pride and the valuations of audiences. Do those results generalize beyond industrial mass societies? To find out, we conducted an experiment among 567 participants in 10 small-scale societies scattered across Central and South America, Africa, and Asia: (i) Bosawás Reserve, Nicaragua; (ii) Cotopaxi, Ecuador; (iii) Drâa-Tafilalet, Morocco; (iv) Enugu, Nigeria; (v) Le Morne, Mauritius; (vi) La Gaulette, Mauritius; (vii) Tuva, Russia; (viii) Shaanxi and Henan, China; (ix) farming communities in Japan; and (x) fishing communities in Japan. Despite widely varying languages, cultures, and subsistence modes, pride in each community closely tracked the valuation of audiences locally (mean r = +0.66) and even across communities (mean r = +0.29). This suggests that the pride system not only develops the same functional architecture everywhere but also operates with a substantial degree of universality in its content.}, } @article {pmid30068601, year = {2018}, author = {Schirmer, J and Dyer, F}, title = {A framework to diagnose factors influencing proenvironmental behaviors in water-sensitive urban design.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7690-E7699}, pmid = {30068601}, issn = {1091-6490}, mesh = {*Environment ; Gardening ; Humans ; Knowledge ; Life Style ; *Water Quality ; }, abstract = {The ongoing challenge of maintaining and improving the quality of water that leaves urban stormwater systems is often addressed using technical rather than social solutions. The need for investment in often expensive water infrastructure can be reduced through better investing in promoting human behaviors that protect water quality as part of water-sensitive urban design (WSUD) initiatives. Successfully achieving this requires understanding factors that influence adoption of proenvironmental behaviors. We review past studies examining this topic and identify that factors influencing adoption of proenvironmental behaviors relevant to WSUD commonly fall into four domains: proenvironmental values and norms, awareness and knowledge of environmental problems and the actions that can address them, proximity and place-based identity, and life-stage and lifestyle factors. We propose the VAIL (values, awareness, identify, lifestyle) framework, based on these four domains and able to be contextualized to specific water-quality problems and individual communities, to assist in diagnosing factors influencing adoption of proenvironmental behaviors. We demonstrate the applicability of the framework in a case study examining adoption of gardening practices that support water quality in Canberra, Australia. We developed 22 locally relevant VAIL indicators and surveyed 3,334 residents to understand engagement in four water-friendly gardening behaviors that help improve water quality in local lakes. In regression modeling, the indicators explained a significant amount of variance in these behaviors and suggested avenues for supporting greater adoption of these behaviors. Predictor variables across all four VAIL domains were significant, highlighting the importance of a multidomain framework.}, } @article {pmid30068600, year = {2018}, author = {Dorrity, MW and Cuperus, JT and Carlisle, JA and Fields, S and Queitsch, C}, title = {Preferences in a trait decision determined by transcription factor variants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7997-E8006}, pmid = {30068600}, issn = {1091-6490}, support = {R01 GM114166/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Amino Acid Substitution ; *DNA-Binding Proteins/genetics/metabolism ; *Models, Genetic ; Mutation, Missense ; *Quantitative Trait, Heritable ; *Response Elements ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; *Transcription Factors/genetics/metabolism ; }, abstract = {Few mechanisms are known that explain how transcription factors can adjust phenotypic outputs to accommodate differing environments. In Saccharomyces cerevisiae, the decision to mate or invade relies on environmental cues that converge on a shared transcription factor, Ste12. Specificity toward invasion occurs via Ste12 binding cooperatively with the cofactor Tec1. Here, we determine the range of phenotypic outputs (mating vs. invasion) of thousands of DNA-binding domain variants in Ste12 to understand how preference for invasion may arise. We find that single amino acid changes in the DNA-binding domain can shift the preference of yeast toward either mating or invasion. These mutations define two distinct regions of this domain, suggesting alternative modes of DNA binding for each trait. We characterize the DNA-binding specificity of wild-type Ste12 to identify a strong preference for spacing and orientation of both homodimeric and heterodimeric sites. Ste12 mutants that promote hyperinvasion in a Tec1-independent manner fail to bind cooperative sites with Tec1 and bind to unusual dimeric Ste12 sites composed of one near-perfect and one highly degenerate site. We propose a model in which Ste12 alone may have evolved to activate invasion genes, which could explain how preference for invasion arose in the many fungal pathogens that lack Tec1.}, } @article {pmid30068529, year = {2018}, author = {Brown, CM}, title = {Careers in Core Facility Management.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a032805}, pmid = {30068529}, issn = {1943-0264}, abstract = {The need for centralized shared core facilities and highly qualified core facility staff is becoming increasingly important in universities, research institutes, and commercial laboratories. With the continued advancement and sophistication of scientific equipment typically comes a larger price tag than can be handled by individual research laboratories. Moreover, the ever-increasing need for researchers to think and act in cross-disciplinary environments, coupled with the increasing sophistication of both the instrumentation and associated technologies, prevents most researchers from becoming "experts" in all areas.At all levels, core facility positions involve a love of technology, working with people, working on many diverse scientific questions, and days full of multitasking. Entry-level positions include basic and advanced technicians that require a BSc or MSc degree and some experience in the field. Midlevel management positions require experience in the field and an MSc or PhD degree. Management experience is a plus but not always required. Scientific directorship positions require a PhD and a keen interest in the technologies that are typically applied in the director's research program. Associate deans of core resources are often former core managers or scientific directors with a vision for the core and who are strong administrators.A career as a core facility staff member can be very rewarding. Successful managers and directors must be able to multitask, reassess priorities, and be adept at using logical reasoning to identify and solve issues as they arise. These positions will continue to be available over the long term with the increasing complexity and continued fast pace of technology development.}, } @article {pmid30068528, year = {2018}, author = {Ule, J and Hwang, HW and Darnell, RB}, title = {The Future of Cross-Linking and Immunoprecipitation (CLIP).}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, pmid = {30068528}, issn = {1943-0264}, support = {//Wellcome Trust/United Kingdom ; R35 NS097404/NS/NINDS NIH HHS/United States ; RC2 NS069473/NS/NINDS NIH HHS/United States ; }, abstract = {SUMMARYTo understand the assembly and functional outcomes of protein-RNA regulation, it is crucial to precisely identify the positions of such interactions. Cross-linking and immunoprecipitation (CLIP) serves this purpose by exploiting covalent protein-RNA cross-linking and RNA fragmentation, along with a series of stringent purification and quality control steps to prepare complementary DNA (cDNA) libraries for sequencing. Here we describe the core steps of CLIP, its primary variations, and the approaches to data analysis. We present the application of CLIP to studies of specific cell types in genetically engineered mice and discuss the mechanistic and physiologic insights that have already been gained from studies using CLIP. We conclude by discussing the future opportunities for CLIP, including studies of human postmortem tissues from disease patients and controls, RNA epigenetic modifications, and RNA structure. These and other applications of CLIP will continue to unravel fundamental gene regulatory mechanisms while providing important biologic and clinically relevant insights.}, } @article {pmid30068397, year = {2018}, author = {Carvalho, SDCES and Grangeiro, CHP and Picanço-Albuquerque, CG and Dos Anjos, TO and De Molfetta, GA and Silva, WA and Ferraz, VEF}, title = {Contribution of SLC26A4 to the molecular diagnosis of nonsyndromic prelingual sensorineural hearing loss in a Brazilian cohort.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {546}, pmid = {30068397}, issn = {1756-0500}, support = {130595/2013-6//CNPq/ ; }, mesh = {Adolescent ; Adult ; Brazil ; Child ; Child, Preschool ; Connexin 26 ; Connexins ; Female ; Hearing Loss ; Hearing Loss, Sensorineural/*genetics ; Humans ; Male ; Membrane Transport Proteins ; Middle Aged ; *Mutation ; Sulfate Transporters/*genetics ; Young Adult ; }, abstract = {OBJECTIVE: Hereditary hearing loss (HL) is the most common sensorineural disorder in humans. Besides mutations in GJB2 and GJB6 genes, pathogenic variants in the SLC26A4 gene have been reported as a cause of hereditary HL due to its role in the physiology of the inner ear. In this research we wanted to investigate the prevalence of mutations in SLC26A4 in Brazilian patients with nonsyndromic prelingual sensorineural HL. We applied the high-resolution melting technique to screen 88 DNA samples from unrelated deaf individuals that were previously screened for GJB2, GJB6 and MT-RNR1 mutations.

RESULTS: The frequency of mutations in the SLC26A4 gene was 28.4%. Two novel mutations were found: p.Ile254Val and p.Asn382Lys. The mutation c.-66C>G (rs17154282) in the promoter region of SLC26A4, was the most frequent mutation found and was significantly associated with nonsyndromic prelingual sensorineural HL. After mutations in the GJB2, GJB6 and mitochondrial genes, SLC26A4 mutations are considered the next most common cause of hereditary HL in Brazilian as well as in other populations, which corroborates with our data. Furthermore, we suggest the inclusion of the SCL26A4 gene in the investigation of hereditary HL since there was an increase in the frequency of the mutations found, up to 22.7%.}, } @article {pmid30068392, year = {2018}, author = {Reba, K and Argaw, Z and Walle, B and Gutema, H}, title = {Health-related quality of life of patients with diagnosed type 2 diabetes in Felege Hiwot Referral Hospital, North West Ethiopia: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {544}, pmid = {30068392}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/*complications ; Ethiopia ; Female ; Humans ; Male ; Middle Aged ; *Quality of Life ; Referral and Consultation ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Diabetes mellitus is a chronic non-communicable disease with considerable impact on health status and quality of life. It has a profound effect on quality of life in terms of social and psychological as well as physical well-being. This study was conducted to assess health related quality of life among patients with diagnosed type 2 diabetes.

RESULT: A cross-sectional study design was conducted from April to May, 2015. World Health Organization quality of life-BREF tool was used for collecting the data. A total of 344 patients with diagnosed type 2 diabetes were involved in the study. The overall health related quality of life mean score of the study participants was 52.6 ± 12.1 SD. Social domain has higher mean score (57.8 ± 14.8 SD). Educational status, marital status, occupation, duration of the diabetes and diabetes related complications had statistically significant association with health-related quality of life. An intervention that give special attention to the breaking of the cycle of low occupational status and literacy; and which encourage patients with type 2 DM to have good control of their diabetes and prevent complication should be implemented to improve their quality of life.}, } @article {pmid30068390, year = {2018}, author = {Parkash, O and Jafri, W and Munir, SM and Iqbal, R}, title = {Assessment of malnutrition in patients with liver cirrhosis using protein calorie malnutrition (PCM) score verses bio-electrical impedance analysis (BIA).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {545}, pmid = {30068390}, issn = {1756-0500}, support = {PMRC Grant No: 4-22-17/08/RDC/AKU//Pakistan Medical and Research Council/ ; }, mesh = {Adult ; Body Composition ; Cross-Sectional Studies ; Electric Impedance ; Humans ; Liver Cirrhosis/*complications ; *Nutrition Assessment ; Nutritional Status ; Pakistan ; *Protein-Energy Malnutrition ; }, abstract = {OBJECTIVE: Malnutrition is a common problem in patients with liver cirrhosis and tools for nutritional assessment are under debate. We conducted this study to assess prevalence of malnutrition in cirrhotic patients using PCM score and BIA. Additionally we compared BIA to PCM score for detecting malnutrition in this patient population.

RESULTS: This was a cross sectional study conducted in two tertiary care hospitals of Karachi Pakistan on adults with liver cirrhosis. Malnutrition was assessed by PCM score using anthropometric measurements and biological specimens and (ii) Body cell mass was assessed using BIA. Malnutrition as estimated by the PCM score was present in 122 (73%) of patients in which most patients had mild malnutrition (n = 72 (45%)), followed by 34 (21%) with moderate malnutrition and 3 (1.9%) with severe malnutrition. Malnutrition according to BIA estimated through body cell mass could detect it in 98 (61%) of patients. There was optimal correlation of PCM score with body call mass (Pearson correlation coefficient = 0.3 (p value 0.001)). We conclude that majority of the patients with liver cirrhosis had malnutrition as determined by PCM score. BIA underscored the malnutrition in this patient population.}, } @article {pmid30068387, year = {2018}, author = {de Melo Lucena, DM and Dos Santos Figueiredo, FW and de Alcantara Sousa, LV and da Silva Paiva, L and do Carmo Almeida, TC and Galego, SJ and Correa, JA and da Silva Maciel, E and Adami, F}, title = {Correlation between municipal human development index and stroke mortality: a study of Brazilian capitals.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {540}, pmid = {30068387}, issn = {1756-0500}, support = {PIBIC (Notice 2015-2016) Institutional Program for Scientific Initiation Scholarship//Programa Institucional de Bolsas de Iniciação Científica/ ; }, mesh = {Brazil/epidemiology ; Humans ; Longevity ; *Social Class ; *Socioeconomic Factors ; Stroke/*mortality ; }, abstract = {OBJECTIVE: To analyze the correlation between municipal human development indices (MHDIs) and stroke mortality in residents of Brazilian state capitals in 2010. A secondary data analysis was conducted in 2015 using data for the MHDI and the following dimensions: income, longevity and education which were obtained from the United Nations Development Program. Additionally, we analyzed age-standardized stroke mortality data from the Department of System Information Unified Health of Brazil.

RESULTS: We observed a correlation between stroke mortality and MHDIs overall (Pearson r = - 0.563; p = 0.002) and within the following dimensions: income (Spearman's ρ = - 0.479; p = 0.011), longevity (Pearson r = - 0.510; p = 0.006) and education (Pearson r = - 0.592; p = 0.001). We identified moderate but significant negative correlations between MHDI overall and in its individual dimensions (income, longevity, and age) and stroke mortality in Brazilian capitals. Stroke is the second leading cause of death in industrialized countries and the leading cause of death in Brazil. Therefore, the discovery of factors that may influence the epidemiology of stroke is important for the construction of adequate policies considering to the socioeconomic status in these places and with an emphasis in lower socioeconomic status places.}, } @article {pmid30068386, year = {2018}, author = {Tolefac, PN and Nana, TN and Yeika, EV and Awungafac, NS and Ntsama, Y and Njotang, PN}, title = {Trends and patterns of family planning methods used among women attending family planning clinic in a rural setting in sub-Sahara Africa: the case of Mbalmayo District Hospital, Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {541}, pmid = {30068386}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Africa South of the Sahara ; Cameroon ; Contraception ; *Contraception Behavior ; Cross-Sectional Studies ; *Family Planning Services ; Female ; Hospitals, District ; Humans ; Middle Aged ; Pregnancy ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: Family planning enables women to prevent unwanted pregnancies and control family sizes. Provision of family planning services is an essential human right. This study aimed to describe the trends and patterns of contraceptive use in a family planning clinic in a rural district hospital setting.

RESULTS: A total 313 participants who used contraceptives between March 2016 and August 2017 were included this study given a. Their mean age was 32.4 ± 1.8 years with an age range of 18-48 years. The index study estimates the rate of contraceptive use at 17.4 contraceptives per month. The most commonly used contraceptive methods were implants and IUD in 29.4 and 28.4% of the participants respectively while the least used was condoms in 8.3% of the participants. Contraceptive used are highest among those 21-40 years (83.1%) and least among adolescents less than 20 years (6.7%).}, } @article {pmid30068385, year = {2018}, author = {Azeze, TK and Sisay, MM and Zeleke, EG}, title = {Incidence of diabetes retinopathy and determinants of time to diabetes retinopathy among diabetes patients at Tikur Anbessa Hospital, Ethiopia: a retrospective follow up study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {542}, pmid = {30068385}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Diabetic Retinopathy/*epidemiology ; Ethiopia/epidemiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Retrospective Studies ; }, abstract = {OBJECTIVE: Data regarding diabetes retinopathy and associated factors are currently lacking in Ethiopia. The study aims to determine the incidence and determinants of time to diabetes retinopathy among diabetes mellitus patients at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

RESULTS: The incidence of diabetes retinopathy is a rapidly growing burden of disease in Ethiopia. The incidence rate of diabetes retinopathy was 2.65 (95% CI 2. 54, 4.05) per 1000 person-years observation. Moreover, 70 (18.57%, 95% CI 14.63, 22.5) DM patients developed diabetes retinopathy. The median time was 74.07 months (with IQR 53.60, 89.88). Male sex (AHR = 1.94, 95% CI = 1.10, 3.39), type 2 DM (AHR = 4.01, 95% CI = 1.34, 12.00), creatinine (AHR = 2.59, 95% CI = 1.91, 3.52), borderline triglyceride (AHR = 2.87, 95% CI 1.33, 6.21) and high triglyceride levels (AHR = 2.59, 95% CI = 1.31, 4.97) were positively correlated factors to diabetes retinopathy occurrence. Multisectoral, population-based approaches are needed to reduce type 2 DM complications.}, } @article {pmid30068381, year = {2018}, author = {Behrouzi, A and Vaziri, F and Riazi Rad, F and Amanzadeh, A and Fateh, A and Moshiri, A and Khatami, S and Siadat, SD}, title = {Comparative study of pathogenic and non-pathogenic Escherichia coli outer membrane vesicles and prediction of host-interactions with TLR signaling pathways.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {539}, pmid = {30068381}, issn = {1756-0500}, support = {809//Institut Pasteur/ ; }, mesh = {Bacterial Outer Membrane Proteins/*physiology ; Epithelial Cells ; Escherichia coli/*physiology ; Humans ; *Inflammation ; *Intestinal Mucosa ; *Signal Transduction ; }, abstract = {OBJECTIVE: The intestine is the major defensive barrier in the body by having more than 60% of the immune cells in the intestinal mucosa. The aim of this study was to evaluate the Toll like receptor (TLR) signaling pathways and immune response profiles, against outer membrane vesicles (OMVs) in pathogenic and non-pathogenic strains of Escherichia coli.

RESULTS: Our results demonstrated that despite inducing inflammatory and regulatory responses to OMVs released by both strains, there is a remarkable difference in the nature and severity of these responses between the two strains. Following the production and release of OMV by the pathogenic strain, the expressions of the pro-inflammatory cytokines were significantly elevated, in comparison to the non-pathogenic strains. Eventually, our findings suggest that OMV released by the pathogen strain might be colonized, causing inflammation, eliminating the tight junctions of epithelial cells and damaging underlying cells, without the presence of IL-17 at the inflammation site. This could have happened to prevent the development of more severe inflammation, which could lead to the inhibition of colonization. The production of IL-10 is also preventing such inflammations. On the other hand, OMV released by non-pathogenic E. coli appears to influence intestinal homeostasis by causing more anti-inflammatory responses and mild inflammation.}, } @article {pmid30068365, year = {2018}, author = {Seid, A and Teklay, H}, title = {Training improved the note taking skill of nursing students in Aksum University; northern Ethiopia: a classroom-based action research.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {543}, pmid = {30068365}, issn = {1756-0500}, mesh = {*Clinical Competence ; Ethiopia ; Humans ; *Learning ; *Students, Nursing ; Universities ; }, abstract = {OBJECTIVE: Note taking is an effective strategy to improve students' learning. It is considered that very few learners are fit enough for basic note taking skill. Thus, this study was aimed to assess note taking skill and motivation for learning of nursing students and to take action on the identified gaps.

RESULTS: The mean note taking skill score is 22.95 ± 4.766. The study demonstrates 9.1% of students had good note taking skill but 54.5 and 36.4% had moderate and poor note taking skills respectively. Regarding learning motivation, 13.6% had motivation and the rest 68.2 and 18.2% had moderate and poor motivation for learning to be a nurse respectively. On the items used to examine motivation, 54.1% of students were less motivated to ask questions in classroom though clarification is needed. Reasons for poor note taking showed 68.2 and 27.3% responded due to "most faculties are simply reading from the slides" and "students are confident that instructors will give slide copies later" respectively were the two main cited reasons respectively. Training nursing students about note taking techniques has made considerable impact on student's learning behavior.}, } @article {pmid30068345, year = {2018}, author = {Bens, M and Szafranski, K and Holtze, S and Sahm, A and Groth, M and Kestler, HA and Hildebrandt, TB and Platzer, M}, title = {Naked mole-rat transcriptome signatures of socially suppressed sexual maturation and links of reproduction to aging.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {77}, pmid = {30068345}, issn = {1741-7007}, abstract = {BACKGROUND: Naked mole-rats (NMRs) are eusocially organized in colonies. Although breeders carry the additional metabolic load of reproduction, they are extremely long-lived and remain fertile throughout their lifespan. This phenomenon contrasts the disposable soma theory of aging stating that organisms can invest their resources either in somatic maintenance, enabling a longer lifespan, or in reproduction, at the cost of longevity. Here, we present a comparative transcriptome analysis of breeders vs. non-breeders of the eusocial, long-lived NMR vs. the polygynous and shorter-lived guinea pig (GP).

RESULTS: Comparative transcriptome analysis of tissue samples from ten organs showed, in contrast to GPs, low levels of differentiation between sexes in adult NMR non-breeders. After transition into breeders, NMR transcriptomes are markedly sex-specific, show pronounced feedback signaling via gonadal steroids, and have similarities to reproductive phenotypes in African cichlid fish, which also exhibit social status changes between dominant and subordinate phenotypes. Further, NMRs show functional enrichment of status-related expression differences associated with aging. Lipid metabolism and oxidative phosphorylation-molecular networks known to be linked to aging-were identified among most affected gene sets. Remarkably and in contrast to GPs, transcriptome patterns associated with longevity are reinforced in NMR breeders.

CONCLUSION: Our results provide comprehensive and unbiased molecular insights into interspecies differences between NMRs and GPs, both in sexual maturation and in the impact of reproduction on longevity. We present molecular evidence that sexual maturation in NMRs is socially suppressed. In agreement with evolutionary theories of aging in eusocial organisms, we have identified transcriptome patterns in NMR breeders that-in contrast to the disposable soma theory of aging-may slow down aging rates and potentially contribute to their exceptional long life- and healthspan.}, } @article {pmid30068331, year = {2018}, author = {Heinze, I and Bens, M and Calzia, E and Holtze, S and Dakhovnik, O and Sahm, A and Kirkpatrick, JM and Szafranski, K and Romanov, N and Sama, SN and Holzer, K and Singer, S and Ermolaeva, M and Platzer, M and Hildebrandt, T and Ori, A}, title = {Species comparison of liver proteomes reveals links to naked mole-rat longevity and human aging.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {82}, pmid = {30068331}, issn = {1741-7007}, abstract = {BACKGROUND: Mammals display a wide range of variation in their lifespan. Investigating the molecular networks that distinguish long- from short-lived species has proven useful to identify determinants of longevity. Here, we compared the livers of young and old long-lived naked mole-rats (NMRs) and the phylogenetically closely related, shorter-lived, guinea pigs using an integrated omics approach.

RESULTS: We found that NMR livers display a unique expression pattern of mitochondrial proteins that results in distinct metabolic features of their mitochondria. For instance, we observed a generally reduced respiration rate associated with lower protein levels of respiratory chain components, particularly complex I, and increased capacity to utilize fatty acids. Interestingly, we show that the same molecular networks are affected during aging in both NMRs and humans, supporting a direct link to the extraordinary longevity of both species. Finally, we identified a novel detoxification pathway linked to longevity and validated it experimentally in the nematode Caenorhabditis elegans.

CONCLUSIONS: Our work demonstrates the benefits of integrating proteomic and transcriptomic data to perform cross-species comparisons of longevity-associated networks. Using a multispecies approach, we show at the molecular level that livers of NMRs display progressive age-dependent changes that recapitulate typical signatures of aging despite the negligible senescence and extraordinary longevity of these rodents.}, } @article {pmid30068321, year = {2018}, author = {Dörler, D and Kropf, M and Laaha, G and Zaller, JG}, title = {Occurrence of the invasive Spanish slug in gardens: can a citizen science approach help deciphering underlying factors?.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {23}, pmid = {30068321}, issn = {1472-6785}, support = {100994//Bundesministerium für Land- und Forstwirtschaft, Umwelt und Wasserwirtschaft/International ; }, abstract = {BACKGROUND: The Spanish slug (Arion vulgaris, also known as A. lusitanicus) is considered one of the most invasive species in agriculture, horticulture and private gardens all over Europe. Although this slug has been problematic for decades, there is still not much known about its occurrence across private gardens and the underlying meteorological and ecological factors. One reason for this knowledge gap is the limited access of researchers to private gardens. Here we used a citizen science approach to overcome this obstacle and examined whether the occurrence of Arionidae in Austrian gardens was associated with meteorological (air temperature, precipitation, global solar radiation, relative humidity) or ecological factors (plant diversity, earthworm activity). Occurrence of the invasive A. vulgaris versus the similar-looking native A. rufus was compared using a DNA-barcoding approach.

RESULTS: Slugs were collected from 1061 gardens from the dry Pannonian lowland to the wet alpine climate (altitudinal range 742 m). Slug abundance in gardens was best explained and negatively associated with the parameters "sum of the mean air temperature in spring", "number of frost days in the previous winter" and "mean daily global solar radiation on the day of data collection". Precipitation, plant diversity and earthworm activity were also related to slug abundance, but positively. Out of our genetic sampling of collected slugs, 92% belonged to A. vulgaris.

CONCLUSIONS: Our study showed that citizen science (i) is a feasible approach to record species occurrence in restricted areas across a wide geographical range and (ii) could be more widely employed in order to identify underlying environmental factors of species occurrence.}, } @article {pmid30068314, year = {2018}, author = {Sabino, M and Cappelli, K and Capomaccio, S and Pascucci, L and Biasato, I and Verini-Supplizi, A and Valiani, A and Trabalza-Marinucci, M}, title = {Dietary supplementation with olive mill wastewaters induces modifications on chicken jejunum epithelial cell transcriptome and modulates jejunum morphology.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {576}, pmid = {30068314}, issn = {1471-2164}, support = {IZSUM 03/14 RC//Italian Ministry of Health/ ; }, mesh = {Animal Feed ; Animals ; Chickens ; Epithelial Cells/chemistry/drug effects/ultrastructure ; Food Additives/chemistry/pharmacology ; Gene Expression Profiling/methods ; Gene Expression Regulation/drug effects ; Jejunum/chemistry/drug effects/*ultrastructure ; Microscopy, Electron, Transmission ; Olive Oil/*chemistry/pharmacology ; Polyphenols/*administration & dosage/pharmacology ; Sequence Analysis, RNA/methods ; Transcriptome/*drug effects ; Waste Water/*chemistry ; }, abstract = {BACKGROUND: The Mediterranean diet is considered one of the healthier food habits and olive oil is one of its key components. Olive oil polyphenols are known to induce beneficial effects in several pathological conditions, such as inflammatory bowel disease, and to contrast the proliferation of cancer cells or hypercholesterolemia. Polyphenols are also present in waste products derived from the olive industry: olive mill wastewaters (OMWW) are rich in polyphenols and there is an increasing interest in using OMWW in animal nutrition. OMWW are attributed with positive effects in promoting chicken performance and the quality of food-derived products. However, a tissue-specific transcriptome target analysis of chickens fed with OMWW has never been attempted.

RESULTS: We explored the effect of dietary OMWW on the intestinal function in broilers. A morphological analysis of the jejunum revealed that OMWW reduced crypt depth, whereas no significant modifications were observed for villus height and the villus height/crypt depth ratio. An RNA Sequencing analysis was performed on isolated, intestinal, epithelial cells and 280 differentially expressed genes were found using a count-based approach. An enrichment analysis revealed that the majority of up regulated genes in the OMWW group were over-represented by the regulation of viral genome replication-related GO-Terms, whereas down regulated genes were mainly involved in cholesterol and lipid metabolism.

CONCLUSIONS: Our study showed how an industrial waste product can be recycled as a feed additive with a positive relapse. OMWW dietary supplementation can be a nutritional strategy to improve chicken performance and health, prevent intestinal damage, enhance innate immunity and regulate cholesterol metabolism and fat deposition.}, } @article {pmid30068313, year = {2018}, author = {Beder, T and Saluz, HP}, title = {Virulence-related comparative transcriptomics of infectious and non-infectious chlamydial particles.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {575}, pmid = {30068313}, issn = {1471-2164}, support = {DFG 83/2013//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Animals ; Bacterial Proteins/*genetics ; Chlamydiaceae Infections/microbiology ; Chlamydiales/*genetics/pathogenicity ; Chlamydophila psittaci/genetics/pathogenicity ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Bacterial ; Genome Size ; Genome, Bacterial ; Humans ; Sequence Analysis, RNA/*methods ; Virulence Factors/genetics ; }, abstract = {BACKGROUND: Members of the phylum Chlamydiae are obligate intracellular pathogens of humans and animals and have a serious impact on host health. They comprise several zoonotic species with varying disease outcomes and prevalence. To investigate differences in virulence, we focused on Chlamydia psittaci, C. abortus and Waddlia chondrophila. Most threatening is C. psittaci, which frequently infects humans and causes psittacosis associated with severe pneumonia. The closest relative of C. psittaci is C. abortus, which shares the vast majority of genes but less frequently infects humans, and causes stillbirth and sepsis. W. chondrophila is more distantly related, and occasional human infections are associated with respiratory diseases or miscarriage. One possible explanation for differences in virulence originate from species-specific genes as well as differentially expressed homologous virulence factors.

RESULTS: RNA-sequencing (RNA-Seq) was applied to purified infectious elementary bodies (EBs) and non-infectious reticulate bodies (RBs) in order to elucidate the transcriptome of the infectious and replicative chlamydial states. The results showed that approximately half of all genes were differentially expressed. For a descriptive comparison, genes were categorised according to their function in the RAST database. This list was extended by the inclusion of inclusion membrane proteins, outer membrane proteins, polymorphic membrane proteins and type III secretion system effectors. In addition, the expression of fifty-six known and a variety of predicted virulence and immunogenic factors with homologs in C. psittaci, C. abortus and W. chondrophila was analysed. To confirm the RNA-Seq results, the expression of nine factors was validated using real-time quantitative polymerase chain reaction (RT-qPCR). Comparison of RNA-Seq and RT-qPCR results showed a high mean Pearson correlation coefficient of 0.95.

CONCLUSIONS: It was shown that both the replicative and infectious chlamydial state contained distinctive transcriptomes and the cellular processes emphasised in EBs and RBs differed substantially based on the chlamydial species. In addition, the very first interspecies transcriptome comparison is presented here, and the considerable differences in expression of homologous virulence factors might contribute to the differing infection rates and disease outcomes of the pathogens. The RNA-Seq results were confirmed by RT-qPCR and demonstrate the feasibility of interspecies transcriptome comparisons in chlamydia.}, } @article {pmid30068312, year = {2018}, author = {Boggiatto, PM and Fitzsimmons, D and Bayles, DO and Alt, D and Vrentas, CE and Olsen, SC}, title = {Coincidence cloning recovery of Brucella melitensis RNA from goat tissues: advancing the in vivo analysis of pathogen gene expression in brucellosis.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {10}, pmid = {30068312}, issn = {1471-2199}, support = {Intramural USDA funding//USDA/International ; }, mesh = {Animals ; Bacterial Proteins/genetics ; Brucella melitensis/*genetics ; Cloning, Molecular/*methods ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Bacterial ; Goats ; Lymph Nodes/*microbiology ; Polymorphism, Single Nucleotide ; RNA, Bacterial/*genetics ; Sequence Analysis, RNA/methods ; }, abstract = {BACKGROUND: Brucella melitensis bacteria cause persistent, intracellular infections in small ruminants as well as in humans, leading to significant morbidity and economic loss worldwide. The majority of experiments on the transcriptional responses of Brucella to conditions inside the host have been performed following invasion of cultured mammalian cells, and do not address gene expression patterns during long-term infection.

RESULTS: Here, we examine the application of the previously developed coincidence cloning methodology to recover and characterize B. melitensis RNA from the supramammary lymph node of experimentally-infected goats. Using coincidence cloning, we successfully recovered Brucella RNA from supramammary lymph nodes of B. melitensis-infected goats at both short-term (4 weeks) and long-term (38 weeks) infection time points. Amplified nucleic acid levels were sufficient for analysis of Brucella gene expression patterns by RNA-sequencing, providing evidence of metabolic activity in both the short-term and the long-term samples. We developed a workflow for the use of sequence polymorphism analysis to confirm recovery of the inoculated strain in the recovered reads, and utilized clustering analysis to demonstrate a distinct transcriptional profile present in samples recovered in long-term infection. In this first look at B. melitensis gene expression patterns in vivo, the subset of Brucella genes that was highly upregulated in long-term as compared to short-term infection included genes linked to roles in murine infection, such as genes involved in proline utilization and signal transduction. Finally, we demonstrated the challenges of qPCR validation of samples with very low ratios of pathogen:host RNA, as is the case during in vivo brucellosis, and alternatively characterized intermediate products of the coincidence cloning reaction.

CONCLUSIONS: Overall, this study provides the first example of recovery plus characterization of B. melitensis RNA from in vivo lymph node infection, and demonstrates that the coincidence cloning technique is a useful tool for characterizing in vivo transcriptional changes in Brucella species. Genes upregulated in long-term infection in this data set, including many genes not previously demonstrated to be virulence factors in mice or macrophage experiments, are candidates of future interest for potential roles in Brucella persistence in natural host systems.}, } @article {pmid30068296, year = {2018}, author = {Rincón, E and Rocha-Gregg, BL and Collins, SR}, title = {A map of gene expression in neutrophil-like cell lines.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {573}, pmid = {30068296}, issn = {1471-2164}, support = {R25 GM056765/GM/NIGMS NIH HHS/United States ; UC Davis Hellman Fellowship//Hellman Foundation/ ; R25 GM056765//National Institute of General Medical Sciences/ ; DP2 HD094656/HD/NICHD NIH HHS/United States ; COR Large Grant Award//University of California, Davis/ ; Kimmel Scholar Award//Sidney Kimmel Foundation/ ; DP2 HD094656//NIH Office of the Director/ ; Floyd and Mary Schwall Fellowship//University of California, Davis/ ; }, mesh = {Animals ; Cell Differentiation ; Cell Line, Tumor ; Cell Proliferation ; Cell Survival ; Culture Media/chemistry ; Dimethyl Sulfoxide/chemistry ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; *Gene Regulatory Networks ; HL-60 Cells ; Humans ; Mice ; Neutrophils/chemistry/*cytology ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Human neutrophils are central players in innate immunity, a major component of inflammatory responses, and a leading model for cell motility and chemotaxis. However, primary neutrophils are short-lived, limiting their experimental usefulness in the laboratory. Thus, human myeloid cell lines have been characterized for their ability to undergo neutrophil-like differentiation in vitro. The HL-60 cell line and its PLB-985 sub-line are commonly used to model human neutrophil behavior, but how closely gene expression in differentiated cells resembles that of primary neutrophils has remained unclear.

RESULTS: In this study, we compared the effectiveness of differentiation protocols and used RNA sequencing (RNA-seq) to compare the transcriptomes of HL-60 and PLB-985 cells with published data for human and mouse primary neutrophils. Among commonly used differentiation protocols for neutrophil-like cell lines, addition of dimethyl sulfoxide (DMSO) gave the best combination of cell viability and expression of markers for differentiation. However, combining DMSO with the serum-free-supplement Nutridoma resulted in increased chemotactic response, phagocytic activity, oxidative burst and cell surface expression of the neutrophil markers FPR1 and CD11b without a cost in viability. RNA-seq analysis of HL-60 and PLB-985 cells before and after differentiation showed that differentiation broadly increases the similarity in gene expression between the cell lines and primary neutrophils. Furthermore, the gene expression pattern of the differentiated cell lines correlated slightly better with that of human neutrophils than the mouse neutrophil pattern did. Finally, we created a publicly available gene expression database that is searchable by gene name and protein domain content, where users can compare gene expression in HL-60, PLB-985 and primary human and mouse neutrophils.

CONCLUSIONS: Our study verifies that a DMSO-based differentiation protocol for HL-60 and PLB-985 cell lines gives superior differentiation and cell viability relative to other common protocols, and indicates that addition of Nutridoma may be preferable for studies of chemotaxis, phagocytosis, or oxidative burst. Our neutrophil gene expression database will be a valuable tool to identify similarities and differences in gene expression between the cell lines and primary neutrophils, to compare expression levels for genes of interest, and to improve the design of tools for genetic perturbations.}, } @article {pmid30068294, year = {2018}, author = {Zhao, Z and Peng, H and Lan, C and Zheng, Y and Fang, L and Li, J}, title = {Imbalance learning for the prediction of N6-Methylation sites in mRNAs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {574}, pmid = {30068294}, issn = {1471-2164}, mesh = {Adenosine/*analogs & derivatives/analysis ; Algorithms ; Computational Biology/economics/*methods ; Humans ; Machine Learning ; RNA, Messenger/*chemistry ; }, abstract = {BACKGROUND: N6-methyladenosine (m6A) is an important epigenetic modification which plays various roles in mRNA metabolism and embryogenesis directly related to human diseases. To identify m6A in a large scale, machine learning methods have been developed to make predictions on m6A sites. However, there are two main drawbacks of these methods. The first is the inadequate learning of the imbalanced m6A samples which are much less than the non-m6A samples, by their balanced learning approaches. Second, the features used by these methods are not outstanding to represent m6A sequence characteristics.

RESULTS: We propose to use cost-sensitive learning ideas to resolve the imbalance data issues in the human mRNA m6A prediction problem. This cost-sensitive approach applies to the entire imbalanced dataset, without random equal-size selection of negative samples, for an adequate learning. Along with site location and entropy features, top-ranked positions with the highest single nucleotide polymorphism specificity in the window sequences are taken as new features in our imbalance learning. On an independent dataset, our overall prediction performance is much superior to the existing predictors. Our method shows stronger robustness against the imbalance changes in the tests on 9 datasets whose imbalance ratios range from 1:1 to 9:1. Our method also outperforms the existing predictors on 1226 individual transcripts. It is found that the new types of features are indeed of high significance in the m6A prediction. The case studies on gene c-Jun and CBFB demonstrate the detailed prediction capacity to improve the prediction performance.

CONCLUSION: The proposed cost-sensitive model and the new features are useful in human mRNA m6A prediction. Our method achieves better correctness and robustness than the existing predictors in independent test and case studies. The results suggest that imbalance learning is promising to improve the performance of m6A prediction.}, } @article {pmid30068293, year = {2018}, author = {Lee, YI and Yap, JW and Izan, S and Leitch, IJ and Fay, MF and Lee, YC and Hidalgo, O and Dodsworth, S and Smulders, MJM and Gravendeel, B and Leitch, AR}, title = {Satellite DNA in Paphiopedilum subgenus Parvisepalum as revealed by high-throughput sequencing and fluorescent in situ hybridization.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {578}, pmid = {30068293}, issn = {1471-2164}, support = {NSC 102-2313-B-178-001-MY3//Ministry of Science and Technology, Taiwan/ ; }, mesh = {Chromosome Mapping ; DNA, Plant/genetics ; DNA, Ribosomal/genetics ; DNA, Satellite/*genetics ; Evolution, Molecular ; High-Throughput Nucleotide Sequencing/*methods ; In Situ Hybridization, Fluorescence/*methods ; Orchidaceae/*genetics ; Phylogeny ; RNA, Ribosomal/genetics ; Sequence Analysis, DNA/*methods ; Species Specificity ; }, abstract = {BACKGROUND: Satellite DNA is a rapidly diverging, largely repetitive DNA component of many eukaryotic genomes. Here we analyse the evolutionary dynamics of a satellite DNA repeat in the genomes of a group of Asian subtropical lady slipper orchids (Paphiopedilum subgenus Parvisepalum and representative species in the other subgenera/sections across the genus). A new satellite repeat in Paphiopedilum subgenus Parvisepalum, SatA, was identified and characterized using the RepeatExplorer pipeline in HiSeq Illumina reads from P. armeniacum (2n = 26). Reconstructed monomers were used to design a satellite-specific fluorescent in situ hybridization (FISH) probe. The data were also analysed within a phylogenetic framework built using the internal transcribed spacer (ITS) sequences of 45S nuclear ribosomal DNA.

RESULTS: SatA comprises c. 14.5% of the P. armeniacum genome and is specific to subgenus Parvisepalum. It is composed of four primary monomers that range from 230 to 359 bp and contains multiple inverted repeat regions with hairpin-loop motifs. A new karyotype of P. vietnamense (2n = 28) is presented and shows that the chromosome number in subgenus Parvisepalum is not conserved at 2n = 26, as previously reported. The physical locations of SatA sequences were visualised on the chromosomes of all seven Paphiopedilum species of subgenus Parvisepalum (2n = 26-28), together with the 5S and 45S rDNA loci using FISH. The SatA repeats were predominantly localisedin the centromeric, peri-centromeric and sub-telocentric chromosome regions, but the exact distribution pattern was species-specific.

CONCLUSIONS: We conclude that the newly discovered, highly abundant and rapidly evolving satellite sequence SatA is specific to Paphiopedilum subgenus Parvisepalum. SatA and rDNA chromosomal distributions are characteristic of species, and comparisons between species reveal that the distribution patterns generate a strong phylogenetic signal. We also conclude that the ancestral chromosome number of subgenus Parvisepalum and indeed of all Paphiopedilum could be either 2n = 26 or 28, if P. vietnamense is sister to all species in the subgenus as suggested by the ITS data.}, } @article {pmid30068292, year = {2018}, author = {Aci, MM and Lupini, A and Mauceri, A and Morsli, A and Khelifi, L and Sunseri, F}, title = {Genetic variation and structure of maize populations from Saoura and Gourara oasis in Algerian Sahara.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {51}, pmid = {30068292}, issn = {1471-2156}, abstract = {BACKGROUND: The ability of maize populations/landraces to tolerate drastically extreme environments over the past four centuries in Algeria leads to characterize these genetic resources for germplasm management as well as the identification of the best landraces useful for genetic improvement. Thus, the aim of the present work was a fingerprinting of an Algerian maize collection (47 landraces) from Saharan oasis by using 24 agro-morphological traits and18 Simple Sequence Repeats to evaluate genetic diversity and population structure.

RESULTS: Phenotypic traits showed large significant variation in which earliness, plant size, ear and kernel features and crop yield appeared the most discriminant traits among landraces by using principal component analysis (PCA). One hundred ninety-seven different alleles were detected with a high mean number of allele per locus (10.9). The selected SSR were highly informative with PIC values > 0.65 as well as an overall genetic diversity (0.47) highlighting a broad genetic variability in the analyzed landraces. Genetic structure analysis revealed a high genetic differentiation among the 47 maize landraces with an overall Fst value (0.33). Cluster analysis for morphological traits as well as for SSR markers grouped the 47 Algerian populations regardless their geographic origin.

CONCLUSIONS: Maize from Algerian desert harbors a wide genetic diversity offering a source of novel/unique alleles useful for maize breeding programs to face the ongoing and future major challenge, the climate changes.}, } @article {pmid30068289, year = {2018}, author = {Cheng, C and Wang, Y and Chai, F and Li, S and Xin, H and Liang, Z}, title = {Genome-wide identification and characterization of the 14-3-3 family in Vitis vinifera L. during berry development and cold- and heat-stress response.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {579}, pmid = {30068289}, issn = {1471-2164}, support = {31572090//National Natural Science Foundation of China/ ; 31772266//National Natural Science Foundation of China/ ; NXNYYZ20150203//Agricultural Breeding Project of Ningxia Hui Autonomous Region/ ; }, mesh = {14-3-3 Proteins/*genetics ; Cold Temperature ; Evolution, Molecular ; Fruit/genetics/growth & development ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Genome, Plant ; Hot Temperature ; Multigene Family ; Phylogeny ; Plant Proteins/genetics ; *Stress, Physiological ; Vitis/genetics/*growth & development ; }, abstract = {BACKGROUND: The 14-3-3 family of ubiquitous proteins in eukaryotes plays important roles in the regulation of various plant biological processes. However, less information is known about this family in grape fruit.

RESULTS: To investigate the characteristics and functions of 14-3-3 in grape, a total of 11 14-3-3 proteins were identified. Phylogenetic analysis of 14-3-3 proteins in grape (VviGRFs) with homologous proteins in Arabidopsis showed that these proteins were classified into two groups, namely, epsilon and non-epsilon groups. Epsilon group members commonly contained more introns and motifs than non-epsilon group, and some intron positions were found to be conserved between Vitis and Arabidopsis 14-3-3 genes. RNA-seq and qRT-PCR results indicated that VviGRF genes may be involved in the regulation of grape development and berry ripening. Moreover, six VviGRFs exhibited significantly up- or down-regulated expression in response to cold and heat stresses, thereby revealing their potential roles in the regulation of abiotic stress responses.

CONCLUSIONS: This work provides fundamental knowledge for further studies about the biological roles of VviGRFs in grape development and abiotic stress response. The present result will also be beneficial for understanding their molecular mechanisms and improving grape agricultural traits in the future.}, } @article {pmid30068288, year = {2018}, author = {Karamitros, T and van Wilgenburg, B and Wills, M and Klenerman, P and Magiorkinis, G}, title = {Nanopore sequencing and full genome de novo assembly of human cytomegalovirus TB40/E reveals clonal diversity and structural variations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {577}, pmid = {30068288}, issn = {1471-2164}, support = {MR/K010565/1//Medical Research Council/United Kingdom ; }, mesh = {Algorithms ; Cell Line ; Cytomegalovirus/*genetics ; Evolution, Molecular ; Genome Size ; *Genome, Viral ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Nanopores ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Human cytomegalovirus (HCMV) has a double-stranded DNA genome of approximately 235 Kbp that is structurally complex including extended GC-rich repeated regions. Genomic recombination events are frequent in HCMV cultures but have also been observed in vivo. Thus, the assembly of HCMV whole genomes from technologies producing shorter than 500 bp sequences is technically challenging. Here we improved the reconstruction of HCMV full genomes by means of a hybrid, de novo genome-assembly bioinformatics pipeline upon data generated from the recently released MinION MkI B sequencer from Oxford Nanopore Technologies.

RESULTS: The MinION run of the HCMV (strain TB40/E) library resulted in ~ 47,000 reads from a single R9 flowcell and in ~ 100× average read depth across the virus genome. We developed a novel, self-correcting bioinformatics algorithm to assemble the pooled HCMV genomes in three stages. In the first stage of the bioinformatics algorithm, long contigs (N50 = 21,892) of lower accuracy were reconstructed. In the second stage, short contigs (N50 = 5686) of higher accuracy were assembled, while in the final stage the high quality contigs served as template for the correction of the longer contigs resulting in a high-accuracy, full genome assembly (N50 = 41,056). We were able to reconstruct a single representative haplotype without employing any scaffolding steps. The majority (98.8%) of the genomic features from the reference strain were accurately annotated on this full genome construct. Our method also allowed the detection of multiple alternative sub-genomic fragments and non-canonical structures suggesting rearrangement events between the unique (UL /US) and the repeated (T/IRL/S) genomic regions.

CONCLUSIONS: Third generation high-throughput sequencing technologies can accurately reconstruct full-length HCMV genomes including their low-complexity and highly repetitive regions. Full-length HCMV genomes could prove crucial in understanding the genetic determinants and viral evolution underpinning drug resistance, virulence and pathogenesis.}, } @article {pmid30067175, year = {2018}, author = {Hwang, WM and Ko, Y and Kang, K and Ahn, TY}, title = {Paludirhabdus telluriireducens gen. nov., sp. nov. and Paludirhabdus pumila sp. nov., isolated from soil of a mountain wetland and emended description of Gorillibacterium massiliense.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3040-3046}, doi = {10.1099/ijsem.0.002946}, pmid = {30067175}, issn = {1466-5034}, mesh = {Bacillales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; *Wetlands ; }, abstract = {Two strains of Gram-stain-positive, endospore-forming, motile by means of peritrichous flagella, aerobic or facultative anaerobic, and rod-shaped bacteria that were designated ON8T and ON6T were isolated from soil collected from a mountain wetland in Gwang-ju, Republic of Korea. The isolates were catalase-positive and oxidase-negative. Cells of ON8T and ON6T grew at 15-35 °C (optimal 30 °C) and 15-40 °C (optimal 30 °C), respectively. The major menaquinone was MK-7 and the major cellular fatty acids (>10 % of the total) were anteiso-C15 : 0, iso-C15 : 0, C14 : 0 and C16 : 0. The predominant polar lipids were diphosphatidylglycerol, aminophospholipid and phospholipid. Meso-diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The DNA G+C contents of strains ON8T and ON6T were 50.6 and 53.5 mol%, respectively, and the 16S rRNA gene sequence analysis showed that the nearest phylogenetic neighbour of both strains was Gorillibacterium massiliense G5T (93.9 %), followed by the members of the genus Paenibacillus in the family Paenibacillaceae. The DNA-DNA hybridization relatedness value between ON8T and ON6T was 44.1 %, which indicated that they represented distinct species. Based on polyphasic characteristics, a novel genus is proposed with the name Paludirhabdus gen. nov., which consists of two species, Paludirhabdus telluriireducens sp. nov. (the type species; type strain ON8T=KACC 19267T=JCM 31958T) and Paludirhabdus pumila sp. nov. (type strain ON6T=KACC 19266T=JCM 31957T).}, } @article {pmid30066663, year = {2018}, author = {Garnier, R and Guyeux, C and Couchot, JF and Salomon, M and Al-Nuaimi, B and AlKindy, B}, title = {Comparison of metaheuristics to measure gene effects on phylogenetic supports and topologies.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {218}, pmid = {30066663}, issn = {1471-2105}, abstract = {BACKGROUND: A huge and continuous increase in the number of completely sequenced chloroplast genomes, available for evolutionary and functional studies in plants, has been observed during the past years. Consequently, it appears possible to build large-scale phylogenetic trees of plant species. However, building such a tree that is well-supported can be a difficult task, even when a subset of close plant species is considered. Usually, the difficulty raises from a few core genes disturbing the phylogenetic information, due for example from problems of homoplasy. Fortunately, a reliable phylogenetic tree can be obtained once these problematic genes are identified and removed from the analysis.Therefore, in this paper we address the problem of finding the largest subset of core genomes which allows to build the best supported tree.

RESULTS: As an exhaustive study of all core genes combination is untractable in practice, since the combinatorics of the situation made it computationally infeasible, we investigate three well-known metaheuristics to solve this optimization problem. More precisely, we design and compare distributed approaches using genetic algorithm, particle swarm optimization, and simulated annealing. The latter approach is a new contribution and therefore is described in details, whereas the two former ones have been already studied in previous works. They have been designed de novo in a new platform, and new experiments have been achieved on a larger set of chloroplasts, to compare together these three metaheuristics.

CONCLUSIONS: The ways genes affect both tree topology and supports are assessed using statistical tools like Lasso or dummy logistic regression, in an hybrid approach of the genetic algorithm. By doing so, we are able to provide the most supported trees based on the largest subsets of core genes.}, } @article {pmid30066662, year = {2018}, author = {Colombo, R and Damiani, C and Gilbert, D and Heiner, M and Mauri, G and Pescini, D}, title = {Emerging ensembles of kinetic parameters to characterize observed metabolic phenotypes.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {251}, pmid = {30066662}, issn = {1471-2105}, abstract = {BACKGROUND: Determining the value of kinetic constants for a metabolic system in the exact physiological conditions is an extremely hard task. However, this kind of information is of pivotal relevance to effectively simulate a biological phenomenon as complex as metabolism.

RESULTS: To overcome this issue, we propose to investigate emerging properties of ensembles of sets of kinetic constants leading to the biological readout observed in different experimental conditions. To this aim, we exploit information retrievable from constraint-based analyses (i.e. metabolic flux distributions at steady state) with the goal to generate feasible values for kinetic constants exploiting the mass action law. The sets retrieved from the previous step will be used to parametrize a mechanistic model whose simulation will be performed to reconstruct the dynamics of the system (until reaching the metabolic steady state) for each experimental condition. Every parametrization that is in accordance with the expected metabolic phenotype is collected in an ensemble whose features are analyzed to determine the emergence of properties of a phenotype. In this work we apply the proposed approach to identify ensembles of kinetic parameters for five metabolic phenotypes of E. Coli, by analyzing five different experimental conditions associated with the ECC2comp model recently published by Hädicke and collaborators.

CONCLUSIONS: Our results suggest that the parameter values of just few reactions are responsible for the emergence of a metabolic phenotype. Notably, in contrast with constraint-based approaches such as Flux Balance Analysis, the methodology used in this paper does not require to assume that metabolism is optimizing towards a specific goal.}, } @article {pmid30066660, year = {2018}, author = {Angelini, C and Bracciali, A and Gilbert, D and Rizzo, R}, title = {Preface to the BMC-CIBB 2015-16 special issue.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {201}, doi = {10.1186/s12859-018-2176-4}, pmid = {30066660}, issn = {1471-2105}, } @article {pmid30066658, year = {2018}, author = {Fornili, M and Boracchi, P and Ambrogi, F and Biganzoli, E}, title = {Modeling the covariates effects on the hazard function by piecewise exponential artificial neural networks: an application to a controlled clinical trial on renal carcinoma.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {186}, pmid = {30066658}, issn = {1471-2105}, abstract = {BACKGROUND: In exploring the time course of a disease to support or generate biological hypotheses, the shape of the hazard function provides relevant information. For long follow-ups the shape of hazard function may be complex, with the presence of multiple peaks. In this paper we present the use of a neural network extension of the piecewise exponential model to study the shape of the hazard function in time in dependence of covariates. The technique is applied to a dataset of 247 renal cell carcinoma patients from a randomized clinical trial.

RESULTS: An interaction effect of treatment with number of metastatic lymph nodes but not with pathologic T-stage is highlighted.

CONCLUSIONS: Piecewise Exponential Artificial Neural Networks demonstrate a clinically useful and flexible tool in assessing interaction or time-dependent effects of the prognostic factors on the hazard function.}, } @article {pmid30066650, year = {2018}, author = {Sardina, DS and Micale, G and Ferro, A and Pulvirenti, A and Giugno, R}, title = {INBIA: a boosting methodology for proteomic network inference.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {188}, pmid = {30066650}, issn = {1471-2105}, abstract = {BACKGROUND: The analysis of tissue-specific protein interaction networks and their functional enrichment in pathological and normal tissues provides insights on the etiology of diseases. The Pan-cancer proteomic project, in The Cancer Genome Atlas, collects protein expressions in human cancers and it is a reference resource for the functional study of cancers. However, established protocols to infer interaction networks from protein expressions are still missing.

RESULTS: We have developed a methodology called Inference Network Based on iRefIndex Analysis (INBIA) to accurately correlate proteomic inferred relations to protein-protein interaction (PPI) networks. INBIA makes use of 14 network inference methods on protein expressions related to 16 cancer types. It uses as reference model the iRefIndex human PPI network. Predictions are validated through non-interacting and tissue specific PPI networks resources. The first, Negatome, takes into account likely non-interacting proteins by combining both structure properties and literature mining. The latter, TissueNet and GIANT, report experimentally verified PPIs in more than 50 human tissues. The reliability of the proposed methodology is assessed by comparing INBIA with PERA, a tool which infers protein interaction networks from Pathway Commons, by both functional and topological analysis.

CONCLUSION: Results show that INBIA is a valuable approach to predict proteomic interactions in pathological conditions starting from the current knowledge of human protein interactions.}, } @article {pmid30066646, year = {2018}, author = {Hassall, KL and Mead, A}, title = {Beyond the one-way ANOVA for 'omics data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {199}, pmid = {30066646}, issn = {1471-2105}, support = {BBS/E/C/000I0210//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/C/000I0420//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: With ever increasing accessibility to high throughput technologies, more complex treatment structures can be assessed in a variety of 'omics applications. This adds an extra layer of complexity to the analysis and interpretation, in particular when inferential univariate methods are applied en masse. It is well-known that mass univariate testing suffers from multiplicity issues and although this has been well documented for simple comparative tests, few approaches have focussed on more complex explanatory structures.

RESULTS: Two frameworks are introduced incorporating corrections for multiplicity whilst maintaining appropriate structure in the explanatory variables. Within this paradigm, a choice has to be made as to whether multiplicity corrections should be applied to the saturated model, putting emphasis on controlling the rate of false positives, or to the predictive model, where emphasis is on model selection. This choice has implications for both the ranking and selection of the response variables identified as differentially expressed. The theoretical difference is demonstrated between the two approaches along with an empirical study of lipid composition in Arabidopsis under differing levels of salt stress.

CONCLUSIONS: Multiplicity corrections have an inherent weakness when the full explanatory structure is not properly incorporated. Although a unifying 'single best' recommendation is not provided, two reasonable alternatives are provided and the applicability of these approaches is discussed for different scenarios where the aims of analysis will differ. The key result is that the point at which multiplicity is incorporated into the analysis will fundamentally change the interpretation of the results, and the choice of approach should therefore be driven by the specific aims of the experiment.}, } @article {pmid30066642, year = {2018}, author = {Gigliarano, C and Nonis, A and Briganti, A and Bonetti, M and Serio, CD}, title = {Effect of the number of removed lymph nodes on prostate cancer recurrence and survival: evidence from an observational study.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {200}, pmid = {30066642}, issn = {1471-2105}, abstract = {BACKGROUND: The aim of this article is to analyze the effect on biochemical recurrence and on overall survival of removing an extensive number of pelvic lymph nodes during prostate cancer surgery. The lack of evidence from randomized clinical trials to address this specific question has hampered the ability to determine the true effect of the number of nodes removed.

RESULTS: Our analysis is based on a large observational study, and this can lead unadjusted estimates to be very sensitive to confounding bias due to the different prognosis of individuals. We assess the effect of the number of lymph nodes removed by means of an Inverse Probability Weighting adjustment based on a Poisson regression model, and by a Doubly-robust adjustment.

CONCLUSIONS: Our findings suggest that a large number of nodes removed is associated with a significant improvement in time to biochemical recurrence. However, it appears to have no impact on overall survival.}, } @article {pmid30066640, year = {2018}, author = {Bardozzo, F and Lió, P and Tagliaferri, R}, title = {A study on multi-omic oscillations in Escherichia coli metabolic networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {194}, pmid = {30066640}, issn = {1471-2105}, abstract = {BACKGROUND: Two important challenges in the analysis of molecular biology information are data (multi-omic information) integration and the detection of patterns across large scale molecular networks and sequences. They are are actually coupled beause the integration of omic information may provide better means to detect multi-omic patterns that could reveal multi-scale or emerging properties at the phenotype levels.

RESULTS: Here we address the problem of integrating various types of molecular information (a large collection of gene expression and sequence data, codon usage and protein abundances) to analyse the E.coli metabolic response to treatments at the whole network level. Our algorithm, MORA (Multi-omic relations adjacency) is able to detect patterns which may represent metabolic network motifs at pathway and supra pathway levels which could hint at some functional role. We provide a description and insights on the algorithm by testing it on a large database of responses to antibiotics. Along with the algorithm MORA, a novel model for the analysis of oscillating multi-omics has been proposed. Interestingly, the resulting analysis suggests that some motifs reveal recurring oscillating or position variation patterns on multi-omics metabolic networks. Our framework, implemented in R, provides effective and friendly means to design intervention scenarios on real data. By analysing how multi-omics data build up multi-scale phenotypes, the software allows to compare and test metabolic models, design new pathways or redesign existing metabolic pathways and validate in silico metabolic models using nearby species.

CONCLUSIONS: The integration of multi-omic data reveals that E.coli multi-omic metabolic networks contain position dependent and recurring patterns which could provide clues of long range correlations in the bacterial genome.}, } @article {pmid30066639, year = {2018}, author = {Conde, S and Xu, X and Guo, H and Perola, M and Fazia, T and Bernardinelli, L and Berzuini, C}, title = {Mendelian randomisation analysis of clustered causal effects of body mass on cardiometabolic biomarkers.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {195}, pmid = {30066639}, issn = {1471-2105}, abstract = {BACKGROUND: Recent advances in data analysis methods based on principles of Mendelian Randomisation, such as Egger regression and the weighted median estimator, add to the researcher's ability to infer cause-effect links from observational data. Now is the time to gauge the potential of these methods within specific areas of biomedical research. In this paper, we choose a study in metabolomics as an illustrative testbed. We apply Mendelian Randomisation methods in the analysis of data from the DILGOM (Dietary, Lifestyle and Genetic determinants of Obesity and Metabolic syndrome) study, in the context of an effort to identify molecular pathways of cardiovascular disease. In particular, our illustrative analysis addresses the question whether body mass, as measured by body mass index (BMI), exerts a causal effect on the concentrations of a collection of 137 cardiometabolic markers with different degrees of atherogenic power, such as the (highly atherogenic) lipoprotein metabolites with very low density (VLDLs) and the (protective) high density lipoprotein metabolites.

RESULTS: We found strongest evidence of a positive BMI effect (that is, evidence that an increase in BMI causes an increase in the metabolite concentration) on those metabolites known to represent strong risk factors for coronary artery disease, such as the VLDLs, and evidence of a negative effect on protective biomarkers.

CONCLUSIONS: The methods discussed represent a useful scientific tool, although they assume the validity of conditions that are (at best) only partially verifiable. This paper provides a rigorous account of such conditions. The results of our analysis provide a proof-of-concept illustration of the potential usefulness of Mendelian Randomisation in genomic biobank studies aiming to dissect the molecular causes of disease, and to identify candidate pharmacological targets.}, } @article {pmid30066633, year = {2018}, author = {Kanhaiya, K and Rogojin, V and Kazemi, K and Czeizler, E and Petre, I}, title = {NetControl4BioMed: a pipeline for biomedical data acquisition and analysis of network controllability.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {185}, pmid = {30066633}, issn = {1471-2105}, abstract = {BACKGROUND: Network controllability focuses on discovering combinations of external interventions that can drive a biological system to a desired configuration. In practice, this approach translates into finding a combined multi-drug therapy in order to induce a desired response from a cell; this can lead to developments of novel therapeutic approaches for systemic diseases like cancer.

RESULT: We develop a novel bioinformatics data analysis pipeline called NetControl4BioMed based on the concept of target structural control of linear networks. Our pipeline generates novel molecular interaction networks by combining pathway data from various public databases starting from the user's query. The pipeline then identifies a set of nodes that is enough to control a given, user-defined set of disease-specific essential proteins in the network, i.e., it is able to induce a change in their configuration from any initial state to any final state. We provide both the source code of the pipeline as well as an online web-service based on this pipeline http://combio.abo.fi/nc/net_control/remote_call.php .

CONCLUSION: The pipeline can be used by researchers for controlling and better understanding of molecular interaction networks through combinatorial multi-drug therapies, for more efficient therapeutic approaches and personalised medicine.}, } @article {pmid30066630, year = {2018}, author = {Saggese, I and Bona, E and Conway, M and Favero, F and Ladetto, M and Liò, P and Manzini, G and Mignone, F}, title = {STAble: a novel approach to de novo assembly of RNA-seq data and its application in a metabolic model network based metatranscriptomic workflow.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {184}, pmid = {30066630}, issn = {1471-2105}, abstract = {BACKGROUND: De novo assembly of RNA-seq data allows the study of transcriptome in absence of a reference genome either if data is obtained from a single organism or from a mixed sample as in metatranscriptomics studies. Given the high number of sequences obtained from NGS approaches, a critical step in any analysis workflow is the assembly of reads to reconstruct transcripts thus reducing the complexity of the analysis. Despite many available tools show a good sensitivity, there is a high percentage of false positives due to the high number of assemblies considered and it is likely that the high frequency of false positive is underestimated by currently used benchmarks. The reconstruction of not existing transcripts may false the biological interpretation of results as - for example - may overestimate the identification of "novel" transcripts. Moreover, benchmarks performed are usually based on RNA-seq data from annotated genomes and assembled transcripts are compared to annotations and genomes to identify putative good and wrong reconstructions, but these tests alone may lead to accept a particular type of false positive as true, as better described below.

RESULTS: Here we present a novel methodology of de novo assembly, implemented in a software named STAble (Short-reads Transcriptome Assembler). The novel concept of this assembler is that the whole reads are used to determine possible alignments instead of using smaller k-mers, with the aim of reducing the number of chimeras produced. Furthermore, we applied a new set of benchmarks based on simulated data to better define the performance of assembly method and carefully identifying true reconstructions. STAble was also used to build a prototype workflow to analyse metatranscriptomics data in connection to a steady state metabolic modelling algorithm. This algorithm was used to produce high quality metabolic interpretations of small gene expression sets obtained from already published RNA-seq data that we assembled with STAble.

CONCLUSIONS: The presented results, albeit preliminary, clearly suggest that with this approach is possible to identify informative reactions not directly revealed by raw transcriptomic data.}, } @article {pmid30066629, year = {2018}, author = {Fiannaca, A and La Paglia, L and La Rosa, M and Lo Bosco, G and Renda, G and Rizzo, R and Gaglio, S and Urso, A}, title = {Deep learning models for bacteria taxonomic classification of metagenomic data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 7}, pages = {198}, pmid = {30066629}, issn = {1471-2105}, abstract = {BACKGROUND: An open challenge in translational bioinformatics is the analysis of sequenced metagenomes from various environmental samples. Of course, several studies demonstrated the 16S ribosomal RNA could be considered as a barcode for bacteria classification at the genus level, but till now it is hard to identify the correct composition of metagenomic data from RNA-seq short-read data. 16S short-read data are generated using two next generation sequencing technologies, i.e. whole genome shotgun (WGS) and amplicon (AMP); typically, the former is filtered to obtain short-reads belonging to a 16S shotgun (SG), whereas the latter take into account only some specific 16S hypervariable regions. The above mentioned two sequencing technologies, SG and AMP, are used alternatively, for this reason in this work we propose a deep learning approach for taxonomic classification of metagenomic data, that can be employed for both of them.

RESULTS: To test the proposed pipeline, we simulated both SG and AMP short-reads, from 1000 16S full-length sequences. Then, we adopted a k-mer representation to map sequences as vectors into a numerical space. Finally, we trained two different deep learning architecture, i.e., convolutional neural network (CNN) and deep belief network (DBN), obtaining a trained model for each taxon. We tested our proposed methodology to find the best parameters configuration, and we compared our results against the classification performances provided by a reference classifier for bacteria identification, known as RDP classifier. We outperformed the RDP classifier at each taxonomic level with both architectures. For instance, at the genus level, both CNN and DBN reached 91.3% of accuracy with AMP short-reads, whereas RDP classifier obtained 83.8% with the same data.

CONCLUSIONS: In this work, we proposed a 16S short-read sequences classification technique based on k-mer representation and deep learning architecture, in which each taxon (from phylum to genus) generates a classification model. Experimental results confirm the proposed pipeline as a valid approach for classifying bacteria sequences; for this reason, our approach could be integrated into the most common tools for metagenomic analysis. According to obtained results, it can be successfully used for classifying both SG and AMP data.}, } @article {pmid30066495, year = {2018}, author = {Wang, Y and Xiao, D and Liu, Q and Zhang, Y and Hu, C and Sun, J and Yang, C and Xu, P and Ma, C and Gao, C}, title = {Two NAD-independent l-lactate dehydrogenases drive l-lactate utilization in Pseudomonas aeruginosa PAO1.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {569-575}, doi = {10.1111/1758-2229.12666}, pmid = {30066495}, issn = {1758-2229}, abstract = {Pseudomonas aeruginosa often establishes a chronic infection in the airways of patients with cystic fibrosis (CF). l-Lactate is the most abundant carbon source in the CF sputum, and l-lactate utilization may be important for P. aeruginosa to survive in the lungs of CF patients. In this study, the key enzymes involved in l-lactate utilization by P. aeruginosa PAO1 were characterized using the synthetic CF sputum medium (SCFM). A highly conserved membrane-bound NAD-independent l-lactate dehydrogenase (l-iLDH) encoded by lldD (PA4771) and a novel flavin-containing membrane-bound l-iLDH encoded by lldA (PA2382) were both found to contribute to l-lactate utilization by P. aeruginosa PAO1. In addition, an lldD and lldA double mutant was incapable of growing in a medium containing l-lactate as the sole carbon source. This study clarifies the mechanism and importance of l-lactate catabolism, and demonstrates the first Pseudomonas spp. expressing two l-lactate-oxidizing enzymes.}, } @article {pmid30066486, year = {2018}, author = {Rascle, C and Dieryckx, C and Dupuy, JW and Muszkieta, L and Souibgui, E and Droux, M and Bruel, C and Girard, V and Poussereau, N}, title = {The pH regulator PacC: a host-dependent virulence factor in Botrytis cinerea.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {555-568}, doi = {10.1111/1758-2229.12663}, pmid = {30066486}, issn = {1758-2229}, abstract = {The phytopathogenic fungus Botrytis cinerea is able to infect a wide variety of plants and plant tissues with differing chemical compositions. During its interaction with the host, this pathogen modulates its ambient pH by secreting acids or ammonia. In this work, we examined the Pal/Pac pathway, the fungal ambient pH-responsive signalling circuit, and investigated the role of the PacC transcription factor. Characterization of the BcpacC deletion mutant revealed an alteration of both fungal growth and virulence depending on the pH of the culture medium or of the host tissue. The pathogenicity of the mutant was altered on plants exhibiting a neutral pH and not on plants with acidic tissues. The capacity of the mutant to acidify its environment and, more particularly, to produce oxalic acid was affected, as was production of reactive oxygen species. Finally, proteomic profiling of the mutant secretome revealed significant changes in plant cell wall polysaccharides proteins and lipid degradation and oxidoreduction, highlighting the importance of BcPacC in the necrotrophic lifestyle of B. cinerea.}, } @article {pmid30066470, year = {2018}, author = {Parmentier, A and Billiet, A and Smagghe, G and Vandamme, P and Deforce, D and Van Nieuwerburgh, F and Meeus, I}, title = {A prokaryotic-eukaryotic relation in the fat body of Bombus terrestris.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {644-650}, doi = {10.1111/1758-2229.12673}, pmid = {30066470}, issn = {1758-2229}, abstract = {The interaction between the insect host and its microbiota plays a central role in insect health and is mostly studied in relation to the digestive system. Nonetheless, there are numerous microorganisms occupying multiple habitats in and on insects. We studied microbial communities in the gut and fat body of bumblebees (Bombus terrestris) using the V4 region of the 16S rRNA gene on the Illumina MiSeq platform. In one of the two study locations, the fat body microbial composition was marked by the dominant presence of Arsenophonus sp. and Phyllobacterium sp. Bumblebees infected with Apicystis bombi, a eukaryotic parasite multiplying in the fat body, had a significant higher relative abundance of Arsenophonus sp. compared with the non-infected individuals. In general, the infection of A. bombi correlated with a more interlinked microbial association network, as we observed an increase of significant associations between the relative abundance of bacteria present in the gut and fat body of infected bumblebees. The causality within this potential prokaryotic-eukaryotic relation is important when assessing the health impact on bees.}, } @article {pmid30066434, year = {2018}, author = {Smith, C and Spence, R and Reichard, M}, title = {Sperm is a sexual ornament in rose bitterling.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1610-1622}, doi = {10.1111/jeb.13357}, pmid = {30066434}, issn = {1420-9101}, support = {P505/12/G112//Czech Science Foundation/ ; }, abstract = {In many taxa, odour cues mediate mating decisions. A key question is what these odours comprise, where they are produced, and what they signal. Using rose bitterling, fish that spawn in the gills of freshwater mussels, we investigated the role of sperm cues on female oviposition decisions using individuals of known MHC genotype. Male bitterling frequently released sperm prior to female oviposition and females responded with an increased probability of oviposition and released a greater number of eggs, particularly if males had a dissimilar MHC genotype. These mating preferences by females were shown to be adaptive, with MHC dissimilarity of males and females correlated positively with embryo survival. These results support a role for indirect benefits to rose bitterling mate choice, and we propose that sperm acts as a releaser pheromone in bitterling, functioning as a sexual ornament signalling male quality as a mate.}, } @article {pmid30066380, year = {2019}, author = {Herrero, A and Flores, E}, title = {Genetic responses to carbon and nitrogen availability in Anabaena.}, journal = {Environmental microbiology}, volume = {21}, number = {1}, pages = {1-17}, doi = {10.1111/1462-2920.14370}, pmid = {30066380}, issn = {1462-2920}, support = {BFU2016-77097-P//Agencia Estatal de Investigación, Spain/ ; BFU2017-88202-P//European Regional Development Fund/ ; }, abstract = {Heterocyst-forming cyanobacteria are filamentous organisms that perform oxygenic photosynthesis and CO2 fixation in vegetative cells and nitrogen fixation in heterocysts, which are formed under deprivation of combined nitrogen. These organisms can acclimate to use different sources of nitrogen and respond to different levels of CO2 . Following work mainly done with the best studied heterocyst-forming cyanobacterium, Anabaena, here we summarize the mechanisms of assimilation of ammonium, nitrate, urea and N2 , the latter involving heterocyst differentiation, and describe aspects of CO2 assimilation that involves a carbon concentration mechanism. These processes are subjected to regulation establishing a hierarchy in the assimilation of nitrogen sources -with preference for the most reduced nitrogen forms- and a dependence on sufficient carbon. This regulation largely takes place at the level of gene expression and is exerted by a variety of transcription factors, including global and pathway-specific transcriptional regulators. NtcA is a CRP-family protein that adjusts global gene expression in response to the C-to-N balance in the cells, and PacR is a LysR-family transcriptional regulator (LTTR) that extensively acclimates the cells to oxygenic phototrophy. A cyanobacterial-specific transcription factor, HetR, is involved in heterocyst differentiation, and other LTTR factors are specifically involved in nitrate and CO2 assimilation.}, } @article {pmid30066155, year = {2018}, author = {Hao, X and Zhang, X and Duan, B and Huo, S and Lin, W and Xia, X and Liu, K}, title = {Screening and Genome Sequencing of Deltamethrin-Degrading Bacterium ZJ6.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1468-1476}, pmid = {30066155}, issn = {1432-0991}, support = {No.5152006//Natural Science Foundation of Beijing, China/ ; }, mesh = {Bacteria/classification/genetics/*isolation & purification/*metabolism ; Biodegradation, Environmental ; *Genome, Bacterial ; Insecticides/*metabolism ; Nitriles/*metabolism ; Phylogeny ; Pyrethrins/*metabolism ; Sequence Analysis, DNA ; Sewage/*microbiology ; Temperature ; }, abstract = {Deltamethrin is a pyrethroid insecticide with high insecticidal activity and a wide range of applications. However, with the increased amount and scope of its application, the accumulated toxicity of deltamethrin has gradually raised concerns. In this study, a bacterium strain, which used deltamethrin as its sole carbon source and was named ZJ6 (Lysinibacillus sp.-ZJ6), was isolated from soil samples collected from the sewage outlet of a pesticide plant in Tianjin. Based on morphological observations of ZJ6, as well as its physiological and biochemical characteristics and 16S rDNA sequence (Gen Bank Accession No. KU129013), the strain was identified as Lysinibacillus fusiformis sp.. A study of the degradation characteristics of ZJ6 revealed that the optimum conditions for shake flask fermentation to degrade deltamethrin by ZJ6 were as follows: pH 7.0, a temperature of 30 °C, a substrate concentration of 100-200 mg/L, an inoculation volume of 10%, and 7 days culturing at 160 rpm. Under these conditions, the degradation rate of deltamethrin by ZJ6 reached 57.2%. Preliminary sequencing of the ZJ6 genome showed that it has a total length of 3,921,852 bp and contains 4567 genes. The average length of each gene in the ZJ6 genome is 859 bp, and these genes account for 84.62% of the total genome length. KEGG metabolic pathway analysis revealed that genes involved in sugar metabolism and metabolism of exogenous chemical substances were significantly enriched in the genome of ZJ6. Comparison with the COG database showed that 2839 of the predicted protein sequences from the ZJ6 genome had COG numbers. Among all protein functions, the number of genes involved in general functions was the highest (372). For the first time, it was found that ZJ6 has relatively strong deltamethrin degradation ability and high value as a subject for further research. In addition, this study provides a reference to guide the preparation of pesticide-degrading bacterial agents and environmental remediation.}, } @article {pmid30066154, year = {2018}, author = {Bhattacharjee, MK and Anees, M and Patel, A}, title = {Increased Viability of Sugar Transport-Deficient Mutant of the Periodontal Pathogen, Aggregatibacter actinomycetemcomitans.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1460-1467}, pmid = {30066154}, issn = {1432-0991}, mesh = {Aggregatibacter actinomycetemcomitans/genetics/*metabolism ; Bacterial Proteins/*genetics/metabolism ; Gene Library ; Humans ; Monosaccharide Transport Proteins/*genetics/metabolism ; Mutation ; Periodontal Diseases/*microbiology ; Sugars/metabolism ; }, abstract = {The periodontal pathogen, Aggregatibacter actinomycetemcomitans is extremely sensitive to even a mildly acidic pH resulting from metabolic acids secreted during growth, losing viability rapidly as the pH goes below 6.0. Cells grown at high glucose concentration grow fast but rapidly lose viability. However, if the cells are grown at low glucose concentration, the pH of the growth medium first decreases slowly for about 24 h and then starts to increase. This increase of pH is indicative of cell death since the spontaneous rise of pH due to the presence of bicarbonate can no longer be opposed by secreted metabolic acids. By monitoring these pH changes on a petri dish, a method was developed to screen for sugar transport-deficient mutants from a library of transposon insertion mutants. Isolation of a mannose phosphotransferase mutant strain is described. The mutant cells were found to be more viable and for a longer period of time than wild-type cells both in high and low glucose concentrations due to slower metabolism and less acid secreted. This observation highlights the concern that spontaneous mutations in the sugar transport genes may be selected for in patients due to increased viability of the mutant cells especially in a biofilm.}, } @article {pmid30066019, year = {2018}, author = {Baumann, K and Dashevsky, D and Sunagar, K and Fry, B}, title = {Scratching the Surface of an Itch: Molecular Evolution of Aculeata Venom Allergens.}, journal = {Journal of molecular evolution}, volume = {86}, number = {7}, pages = {484-500}, pmid = {30066019}, issn = {1432-1432}, abstract = {Hymenopteran insects are infamous for their sting, and their ability to cause severe anaphylaxis and in some cases death. This allergic reaction is a result of allergens present in the venom. Hymenopterans have many common venom allergens, the most widespread of which include phospholipase A1, phospholipase A2, acid phosphatase, hyaluronidase, serine protease and antigen 5. While there have been studies that look at the phylogenetic histories of allergens within closely related species, to our knowledge, this is the first study using evolutionary analyses to compare across Hymenoptera the types of selection that are occurring on allergens. This research examined the publicly available sequences of six different groups of allergens and found that allergens had diverged and formed closely related clades which share greater sequence similarities. We also analysed the patterns of selection and found that they are predominately under the influence of negative selection.}, } @article {pmid30065360, year = {2018}, author = {Du Toit, A}, title = {Bearing the load.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {521}, doi = {10.1038/s41579-018-0067-3}, pmid = {30065360}, issn = {1740-1534}, } @article {pmid30065359, year = {2018}, author = {Du Toit, A}, title = {Continued risk of Ebola virus outbreak.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {521}, doi = {10.1038/s41579-018-0069-1}, pmid = {30065359}, issn = {1740-1534}, } @article {pmid30065354, year = {2018}, author = {Keating, JN and Marquart, CL and Marone, F and Donoghue, PCJ}, title = {The nature of aspidin and the evolutionary origin of bone.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1501-1506}, pmid = {30065354}, issn = {2397-334X}, abstract = {Bone is the key innovation underpinning the evolution of the vertebrate skeleton, yet its origin is mired by debate over interpretation of the most primitive bone-like tissue, aspidin. This has variously been interpreted as cellular bone, acellular bone, dentine or an intermediate of dentine and bone. The crux of the controversy is the nature of unmineralized spaces pervading the aspidin matrix, which have alternatively been interpreted as having housed cells, cell processes or Sharpey's fibres. Discriminating between these hypotheses has been hindered by the limits of traditional histological methods. Here, we use synchrotron X-ray tomographic microscopy to reveal the nature of aspidin. We show that the spaces exhibit a linear morphology incompatible with interpretations that they represent voids left by cells or cell processes. Instead, these spaces represent intrinsic collagen fibre bundles that form a scaffold about which mineral was deposited. Aspidin is thus acellular dermal bone. We reject hypotheses that it is a type of dentine, cellular bone or transitional tissue. Our study suggests that the full repertoire of skeletal tissue types was established before the divergence of the earliest known skeletonizing vertebrates, indicating that the corresponding cell types evolved rapidly following the divergence of cyclostomes and gnathostomes.}, } @article {pmid30065341, year = {2018}, author = {Kruger, P}, title = {Why it is not a 'failure' to leave academia.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {133-134}, doi = {10.1038/d41586-018-05838-y}, pmid = {30065341}, issn = {1476-4687}, mesh = {*Academic Success ; *Career Choice ; Education, Graduate/*methods ; Employee Performance Appraisal ; Humans ; *Mentoring ; *Mentors/psychology ; Research Personnel/*psychology ; Students/*psychology ; Vocational Guidance ; }, } @article {pmid30065340, year = {2018}, author = {Bowman, D}, title = {Wildfire science is at a loss for comprehensive data.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {7}, doi = {10.1038/d41586-018-05840-4}, pmid = {30065340}, issn = {1476-4687}, mesh = {Climate Change ; *Fires ; Forests ; *Wildfires ; }, } @article {pmid30065339, year = {2018}, author = {Mitchinson, A}, title = {The origin of blue diamonds.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {35}, doi = {10.1038/d41586-018-05830-6}, pmid = {30065339}, issn = {1476-4687}, mesh = {*Boron ; Color ; *Diamond ; Earth (Planet) ; }, } @article {pmid30065338, year = {2018}, author = {Kabeer, A and Tsai, JW}, title = {Rectify biased interpretation of science history.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {29}, doi = {10.1038/d41586-018-05848-w}, pmid = {30065338}, issn = {1476-4687}, mesh = {Culture ; Egypt ; History, Ancient ; *Prejudice ; Science/*history ; Stereotyping ; }, } @article {pmid30065337, year = {2018}, author = {Eufemia, L and Bonatti, M and Lana, MA}, title = {Colombia's rural development must honour peace agreement.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {29}, doi = {10.1038/d41586-018-05847-x}, pmid = {30065337}, issn = {1476-4687}, mesh = {Colombia ; *Demography ; Developing Countries ; Forests ; *Social Planning ; }, } @article {pmid30065336, year = {2018}, author = {}, title = {From the archive.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {38}, doi = {10.1038/d41586-018-05843-1}, pmid = {30065336}, issn = {1476-4687}, } @article {pmid30065335, year = {2018}, author = {Zhou, Y and Liu, Y}, title = {Solar power brings money to rural areas.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {29}, doi = {10.1038/d41586-018-05846-y}, pmid = {30065335}, issn = {1476-4687}, } @article {pmid30065334, year = {2018}, author = {de Rijcke, S and Penders, B}, title = {Resist calls for replicability in the humanities.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {29}, doi = {10.1038/d41586-018-05845-z}, pmid = {30065334}, issn = {1476-4687}, mesh = {*Curriculum ; *Humanities ; }, } @article {pmid30065333, year = {2018}, author = {Phillips, N}, title = {Chinese vaccine scandal unlikely to dent childhood immunization rates.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {14-15}, doi = {10.1038/d41586-018-05835-1}, pmid = {30065333}, issn = {1476-4687}, mesh = {Child ; Humans ; *Immunization ; Infant ; Vaccination ; *Vaccines ; }, } @article {pmid30065332, year = {2018}, author = {Prieto, D}, title = {Make research-paper databases multilingual.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {29}, doi = {10.1038/d41586-018-05844-0}, pmid = {30065332}, issn = {1476-4687}, mesh = {*Databases, Bibliographic ; *Internationality ; *Language ; *Research ; *Research Report ; *Translations ; }, } @article {pmid30065331, year = {2018}, author = {Cramton, P and Geddes, RR and Ockenfels, A}, title = {Set road charges in real time to ease traffic.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {23-25}, doi = {10.1038/d41586-018-05836-0}, pmid = {30065331}, issn = {1476-4687}, mesh = {Automobile Driving/psychology/*statistics & numerical data ; City Planning/*economics/*methods ; Humans ; Motor Vehicles/economics ; Public Health ; Stress, Psychological ; *Taxes ; Time Factors ; Traffic-Related Pollution/prevention & control/statistics & numerical data ; Travel/*economics/*statistics & numerical data ; }, } @article {pmid30065330, year = {2018}, author = {}, title = {A single gene helps to enthrone an ant queen.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {9}, doi = {10.1038/d41586-018-05831-5}, pmid = {30065330}, issn = {1476-4687}, } @article {pmid30065329, year = {2018}, author = {Rehm, J}, title = {Push to weaken US Endangered Species Act runs into roadblocks.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {17-18}, doi = {10.1038/d41586-018-05834-2}, pmid = {30065329}, issn = {1476-4687}, mesh = {Administrative Personnel ; Animals ; Conservation of Natural Resources/*legislation & jurisprudence ; Endangered Species/*legislation & jurisprudence ; Extinction, Biological ; *Politics ; Uncertainty ; United States ; }, } @article {pmid30065328, year = {2018}, author = {}, title = {Pirouetting particles twirl at one billion times a second.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {9}, doi = {10.1038/d41586-018-05804-8}, pmid = {30065328}, issn = {1476-4687}, } @article {pmid30065327, year = {2018}, author = {}, title = {Green power in Europe comes at a cost.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {9}, doi = {10.1038/d41586-018-05820-8}, pmid = {30065327}, issn = {1476-4687}, } @article {pmid30065326, year = {2018}, author = {}, title = {When Sherlock Holmes enters the quantum realm.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {8}, doi = {10.1038/d41586-018-05786-7}, pmid = {30065326}, issn = {1476-4687}, } @article {pmid30065325, year = {2018}, author = {Witze, A}, title = {Milky Way's black hole provides long-sought test of Einstein's general relativity.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {17}, doi = {10.1038/d41586-018-05825-3}, pmid = {30065325}, issn = {1476-4687}, } @article {pmid30065324, year = {2018}, author = {}, title = {Why spit is key to building a butterfly.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {9}, doi = {10.1038/d41586-018-05802-w}, pmid = {30065324}, issn = {1476-4687}, } @article {pmid30065323, year = {2018}, author = {Witze, A}, title = {There's water on Mars! Signs of buried lake tantalize scientists.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {13-14}, doi = {10.1038/d41586-018-05795-6}, pmid = {30065323}, issn = {1476-4687}, } @article {pmid30065322, year = {2018}, author = {Callaway, E}, title = {CRISPR plants now subject to tough GM laws in European Union.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {16}, doi = {10.1038/d41586-018-05814-6}, pmid = {30065322}, issn = {1476-4687}, mesh = {Agriculture/economics/legislation & jurisprudence/methods ; CRISPR-Cas Systems/*genetics ; *European Union ; *Food, Genetically Modified/economics/standards ; Gene Editing/*legislation & jurisprudence/standards/trends ; Humans ; Mutagenesis ; Plant Breeding/economics/legislation & jurisprudence/methods ; Research/*legislation & jurisprudence/trends ; }, } @article {pmid30065321, year = {2018}, author = {}, title = {A dinosaur that stomped the Jurassic scene on size XXXXL feet.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {8}, doi = {10.1038/d41586-018-05816-4}, pmid = {30065321}, issn = {1476-4687}, } @article {pmid30065320, year = {2018}, author = {}, title = {A transformation of powder to plastic is a piece of cake.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {8-9}, doi = {10.1038/d41586-018-05785-8}, pmid = {30065320}, issn = {1476-4687}, } @article {pmid30065319, year = {2018}, author = {}, title = {Suicides rise with temperature in much of North America.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {9}, doi = {10.1038/d41586-018-05783-w}, pmid = {30065319}, issn = {1476-4687}, } @article {pmid30065318, year = {2018}, author = {}, title = {Antibiotic resistance lurks below the surface of fish-farm ponds.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {8}, doi = {10.1038/d41586-018-05787-6}, pmid = {30065318}, issn = {1476-4687}, } @article {pmid30065117, year = {2018}, author = {Li, JT and Gao, YD and Xie, L and Deng, C and Shi, P and Guan, ML and Huang, S and Ren, JL and Wu, DD and Ding, L and Huang, ZY and Nie, H and Humphreys, DP and Hillis, DM and Wang, WZ and Zhang, YP}, title = {Comparative genomic investigation of high-elevation adaptation in ectothermic snakes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8406-8411}, pmid = {30065117}, issn = {1091-6490}, mesh = {Acclimatization/*physiology ; Alleles ; *Altitude ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Evolution, Molecular ; Female ; Flap Endonucleases/genetics ; Genome ; Hypoxia ; Phylogeny ; Selection, Genetic ; Snakes/*genetics/physiology ; Tibet ; Ultraviolet Rays ; }, abstract = {Several previous genomic studies have focused on adaptation to high elevations, but these investigations have been largely limited to endotherms. Snakes of the genus Thermophis are endemic to the Tibetan plateau and therefore present an opportunity to study high-elevation adaptations in ectotherms. Here, we report the de novo assembly of the genome of a Tibetan hot-spring snake (Thermophis baileyi) and then compare its genome to the genomes of the other two species of Thermophis, as well as to the genomes of two related species of snakes that occur at lower elevations. We identify 308 putative genes that appear to be under positive selection in Thermophis We also identified genes with shared amino acid replacements in the high-elevation hot-spring snakes compared with snakes and lizards that live at low elevations, including the genes for proteins involved in DNA damage repair (FEN1) and response to hypoxia (EPAS1). Functional assays of the FEN1 alleles reveal that the Thermophis allele is more stable under UV radiation than is the ancestral allele found in low-elevation lizards and snakes. Functional assays of EPAS1 alleles suggest that the Thermophis protein has lower transactivation activity than the low-elevation forms. Our analysis identifies some convergent genetic mechanisms in high-elevation adaptation between endotherms (based on studies of mammals) and ectotherms (based on our studies of Thermophis).}, } @article {pmid30065116, year = {2018}, author = {Kim, H and Kim, HJ and Vu, QT and Jung, S and McClung, CR and Hong, S and Nam, HG}, title = {Circadian control of ORE1 by PRR9 positively regulates leaf senescence in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8448-8453}, pmid = {30065116}, issn = {1091-6490}, mesh = {Aging ; Arabidopsis/*physiology ; Arabidopsis Proteins/genetics/*physiology ; Circadian Rhythm/*physiology ; MicroRNAs/physiology ; Plant Leaves/physiology ; Promoter Regions, Genetic ; Transcription Factors/genetics/*physiology ; }, abstract = {The circadian clock coordinates the daily cyclic rhythm of numerous biological processes by regulating a large portion of the transcriptome. In animals, the circadian clock is involved in aging and senescence, and circadian disruption by mutations in clock genes frequently accelerates aging. Conversely, aging alters circadian rhythmicity, which causes age-associated physiological alterations. However, interactions between the circadian clock and aging have been rarely studied in plants. Here, we investigated potential roles for the circadian clock in the regulation of leaf senescence in plants. Members of the evening complex in Arabidopsis circadian clock, EARLY FLOWERING 3 (ELF3), EARLY FLOWERING 4 (ELF4), and LUX ARRHYTHMO (LUX), as well as the morning component PSEUDO-RESPONSE REGULATOR 9 (PRR9), affect both age-dependent and dark-induced leaf senescence. The circadian clock regulates the expression of several senescence-related transcription factors. In particular, PRR9 binds directly to the promoter of the positive aging regulator ORESARA1 (ORE1) gene to promote its expression. PRR9 also represses miR164, a posttranscriptional repressor of ORE1 Consistently, genetic analysis revealed that delayed leaf senescence of a prr9 mutant was rescued by ORE1 overexpression. Thus, PRR9, a core circadian component, is a key regulator of leaf senescence via positive regulation of ORE1 through a feed-forward pathway involving posttranscriptional regulation by miR164 and direct transcriptional regulation. Our results indicate that, in plants, the circadian clock and leaf senescence are intimately interwoven as are the clock and aging in animals.}, } @article {pmid30065115, year = {2018}, author = {Glantz, ST and Berlew, EE and Jaber, Z and Schuster, BS and Gardner, KH and Chow, BY}, title = {Directly light-regulated binding of RGS-LOV photoreceptors to anionic membrane phospholipids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7720-E7727}, pmid = {30065115}, issn = {1091-6490}, support = {R21 DA040434/DA/NIDA NIH HHS/United States ; T32 NS091006/NS/NINDS NIH HHS/United States ; R01 NS101106/NS/NINDS NIH HHS/United States ; R01 GM106239/GM/NIGMS NIH HHS/United States ; F32 GM119430/GM/NIGMS NIH HHS/United States ; }, mesh = {Botrytis/*chemistry/genetics/metabolism ; Fungal Proteins/*chemistry/genetics/metabolism ; Membrane Proteins/*chemistry/genetics/metabolism ; Phospholipids/*chemistry/metabolism ; }, abstract = {We report natural light-oxygen-voltage (LOV) photoreceptors with a blue light-switched, high-affinity (KD ∼ 10-7 M), and direct electrostatic interaction with anionic phospholipids. Membrane localization of one such photoreceptor, BcLOV4 from Botrytis cinerea, is directly coupled to its flavin photocycle, and is mediated by a polybasic amphipathic helix in the linker region between the LOV sensor and its C-terminal domain of unknown function (DUF), as revealed through a combination of bioinformatics, computational protein modeling, structure-function studies, and optogenetic assays in yeast and mammalian cell line expression systems. In model systems, BcLOV4 rapidly translocates from the cytosol to plasma membrane (∼1 second). The reversible electrostatic interaction is nonselective among anionic phospholipids, exhibiting binding strengths dependent on the total anionic content of the membrane without preference for a specific headgroup. The in vitro and cellular responses were also observed with a BcLOV4 homolog and thus are likely to be general across the dikarya LOV class, whose members are associated with regulator of G-protein signaling (RGS) domains. Natural photoreceptors are not previously known to directly associate with membrane phospholipids in a light-dependent manner, and thus this work establishes both a photosensory signal transmission mode and a single-component optogenetic tool with rapid membrane localization kinetics that approaches the diffusion limit.}, } @article {pmid30065114, year = {2018}, author = {Khoriaty, R and Hesketh, GG and Bernard, A and Weyand, AC and Mellacheruvu, D and Zhu, G and Hoenerhoff, MJ and McGee, B and Everett, L and Adams, EJ and Zhang, B and Saunders, TL and Nesvizhskii, AI and Klionsky, DJ and Shavit, JA and Gingras, AC and Ginsburg, D}, title = {Functions of the COPII gene paralogs SEC23A and SEC23B are interchangeable in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7748-E7757}, pmid = {30065114}, issn = {1091-6490}, support = {T32 HL007622/HL/NHLBI NIH HHS/United States ; P01 HL057346/HL/NHLBI NIH HHS/United States ; R35 HL135793/HL/NHLBI NIH HHS/United States ; P30 CA046592/CA/NCI NIH HHS/United States ; R01 HL094505/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; FDN 143301//CIHR/Canada ; R01 GM053396/GM/NIGMS NIH HHS/United States ; R01 HL039693/HL/NHLBI NIH HHS/United States ; R01 GM094231/GM/NIGMS NIH HHS/United States ; R01 HL124232/HL/NHLBI NIH HHS/United States ; K08 HL128794/HL/NHLBI NIH HHS/United States ; T32 GM007315/GM/NIGMS NIH HHS/United States ; }, mesh = {Anemia, Dyserythropoietic, Congenital/genetics/metabolism ; Bone Marrow/metabolism/pathology ; COP-Coated Vesicles/genetics/*metabolism ; Erythrocytes/*metabolism/pathology ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Multiprotein Complexes/*biosynthesis/genetics ; Species Specificity ; Vesicular Transport Proteins/*biosynthesis/genetics ; }, abstract = {Approximately one-third of the mammalian proteome is transported from the endoplasmic reticulum-to-Golgi via COPII-coated vesicles. SEC23, a core component of coat protein-complex II (COPII), is encoded by two paralogous genes in vertebrates (Sec23a and Sec23b). In humans, SEC23B deficiency results in congenital dyserythropoietic anemia type-II (CDAII), while SEC23A deficiency results in a skeletal phenotype (with normal red blood cells). These distinct clinical disorders, together with previous biochemical studies, suggest unique functions for SEC23A and SEC23B. Here we show indistinguishable intracellular protein interactomes for human SEC23A and SEC23B, complementation of yeast Sec23 by both human and murine SEC23A/B, and rescue of the lethality of sec23b deficiency in zebrafish by a sec23a-expressing transgene. We next demonstrate that a Sec23a coding sequence inserted into the murine Sec23b locus completely rescues the lethal SEC23B-deficient pancreatic phenotype. We show that SEC23B is the predominantly expressed paralog in human bone marrow, but not in the mouse, with the reciprocal pattern observed in the pancreas. Taken together, these data demonstrate an equivalent function for SEC23A/B, with evolutionary shifts in the transcription program likely accounting for the distinct phenotypes of SEC23A/B deficiency within and across species, a paradigm potentially applicable to other sets of paralogous genes. These findings also suggest that enhanced erythroid expression of the normal SEC23A gene could offer an effective therapeutic approach for CDAII patients.}, } @article {pmid30065113, year = {2018}, author = {Deng, L and Chang, TZ and Wang, Y and Li, S and Wang, S and Matsuyama, S and Yu, G and Compans, RW and Li, JD and Prausnitz, MR and Champion, JA and Wang, BZ}, title = {Heterosubtypic influenza protection elicited by double-layered polypeptide nanoparticles in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7758-E7767}, pmid = {30065113}, issn = {1091-6490}, support = {R01 AI101047/AI/NIAID NIH HHS/United States ; R01 AI116835/AI/NIAID NIH HHS/United States ; R01 DC013833/DC/NIDCD NIH HHS/United States ; R01 DC015557/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/*immunology ; Female ; Immunization ; Influenza A virus/*immunology ; Influenza Vaccines/*immunology ; Mice ; Mice, Inbred BALB C ; *Nanoparticles ; Orthomyxoviridae Infections/*immunology/pathology/prevention & control ; Peptides/*immunology ; Receptors, IgG/immunology ; Viral Matrix Proteins/*immunology ; }, abstract = {Influenza is a persistent threat to public health. Here we report that double-layered peptide nanoparticles induced robust specific immunity and protected mice against heterosubtypic influenza A virus challenges. We fabricated the nanoparticles by desolvating a composite peptide of tandem copies of nucleoprotein epitopes into nanoparticles as cores and cross-linking another composite peptide of four tandem copies of influenza matrix protein 2 ectodomain epitopes to the core surfaces as a coating. Delivering the nanoparticles via dissolvable microneedle patch-based skin vaccination further enhanced the induced immunity. These peptide-only, layered nanoparticles demonstrated a strong antigen depot effect and migrated into spleens and draining (inguinal) lymph nodes for an extended period compared with soluble antigens. This increased antigen-presentation time correlated with the stronger immune responses in the nanoparticle-immunized group. The protection conferred by nanoparticle immunization was transferable by passive immune serum transfusion and depended partially on a functional IgG receptor FcγRIV. Using a conditional cell depletion, we found that CD8+ T cells were involved in the protection. The immunological potency and stability of the layered peptide nanoparticles indicate applications for other peptide-based vaccines and peptide drug delivery.}, } @article {pmid30065101, year = {2018}, author = {Carey, J}, title = {News Feature: The race to extinguish insect pests by enlisting their own kind.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7839-7843}, pmid = {30065101}, issn = {1091-6490}, mesh = {Animals ; *Diptera ; Florida ; Humans ; *Insect Control ; Screw Worm Infection/epidemiology/*prevention & control ; United States/epidemiology ; United States Department of Agriculture ; }, } @article {pmid30064903, year = {2018}, author = {Pala, ZR and Saxena, V and Saggu, GS and Garg, S}, title = {Recent Advances in the [Fe-S] Cluster Biogenesis (SUF) Pathway Functional in the Apicoplast of Plasmodium.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {800-809}, doi = {10.1016/j.pt.2018.05.010}, pmid = {30064903}, issn = {1471-5007}, abstract = {Iron-sulfur [Fe-S] clusters are one of the most ancient, ubiquitous, structurally and functionally versatile natural biosynthetic prosthetic groups required by various proteins involved in important metabolic processes. Genome mining and localization studies in Plasmodium have shown two evolutionarily distinct biogenesis pathways: the ISC pathway in mitochondria and the SUF pathway in the apicoplast. In recent years, the myriad efforts made to elucidate the SUF pathway have deciphered the role of various proteins involved in the pathway and their importance for the parasite life cycle in both asexual and sexual stages. This review aims to discuss recent research in the apicoplast [Fe-S] biogenesis pathway from Plasmodium to enhance our current understanding of parasite biology with an overall aim to identify gaps to strengthen our fight against malaria.}, } @article {pmid30064902, year = {2018}, author = {Diemert, DJ and Bottazzi, ME and Plieskatt, J and Hotez, PJ and Bethony, JM}, title = {Lessons along the Critical Path: Developing Vaccines against Human Helminths.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {747-758}, doi = {10.1016/j.pt.2018.07.005}, pmid = {30064902}, issn = {1471-5007}, abstract = {Helminthic parasites are important targets for vaccine research as they infect an estimated 1 billion people worldwide. Despite significant progress in the discovery of defined antigens as candidates for vaccines, the potential of a helminth vaccine advancing to an investigational product to be tested in humans remains as challenging as it did 50 years ago. Candidate helminth vaccines must still advance along a 'critical path' of preclinical research, vaccine process development (which includes 'chemistry, manufacturing, and controls' or CMC), current good manufacturing practice (cGMP) production of the vaccine, and clinical trials. This path is highly targeted towards meeting the safety, immunogenicity, and efficacy criteria of regulatory bodies such as the US Food and Drug Administration (FDA). For nearly 20 years our product development partnership (PDP), the Texas Children's Hospital Center for Vaccine Development (TCH-CVD), has followed the critical paths of several novel subunit vaccines for the human hookworm Necator americanus and the intestinal trematode Schistosoma mansoni. Herein, we describe the critical lessons learned along this critical path.}, } @article {pmid30064526, year = {2018}, author = {van de Loo, AJAE and van Schrojenstein Lantman, M and Mackus, M and Scholey, A and Verster, JC}, title = {Impact of mental resilience and perceived immune functioning on the severity of alcohol hangover.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {526}, pmid = {30064526}, issn = {1756-0500}, mesh = {Adaptation, Psychological ; Adolescent ; Adult ; Alcohol Drinking ; *Alcoholic Intoxication ; *Blood Alcohol Content ; Female ; Humans ; *Immunity ; Male ; Perception ; *Self Concept ; Students ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Recent research comparing hangover sensitive drinkers with hangover resistant drinkers has revealed that experiencing alcohol hangovers is associated with significantly poorer self-reported immune functioning (p < 0.0001). No significant difference between the groups was found on mental resilience. The objective of the current survey was to examine the association between hangover severity, perceived immune status, and mental resilience. N = 341 Dutch students, all hangover sensitive drinkers, completed an online survey. The Brief Resilience Scale was completed, and perceived immune functioning and overall hangover severity for their latest past month hangover were assessed.

RESULTS: Students consumed a mean (SD) of 12.3 (5.9) alcoholic drinks the evening before their latest hangover. A significant positive association was found between mental resilience and perceived immune functioning (r = 0.372, p = 0.000). No significant associations of hangover severity were found with mental resilience (r = - 0.010, p = 0.858), or perceived immune functioning (r = - 0.025, p = 0.645). Previous research revealed that hangover resistant and hangover sensitive drinkers report having significantly different levels of immune functioning, and that the immune system is involved in the development of alcohol hangover. These findings suggest that levels of mental resilience and perceived immune functioning are not related to the severity of hangovers in hangover sensitive drinkers.}, } @article {pmid30064524, year = {2018}, author = {Pappada, SM and Woodling, K and Owais, MH and Zink, EM and Dahbour, L and Tripathi, RS and Khuder, SA and Papadimos, TJ}, title = {Continuous glucose monitoring identifies relationship between optimized glycemic control and post-discharge acute care facility needs.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {533}, pmid = {30064524}, issn = {1756-0500}, mesh = {Aged ; Blood Glucose/*analysis ; Blood Glucose Self-Monitoring ; Diabetes Mellitus, Type 2/*diagnosis/drug therapy ; Female ; Humans ; Hyperglycemia/diagnosis ; Hypoglycemic Agents/*therapeutic use ; Insulin/therapeutic use ; Male ; Middle Aged ; *Patient Discharge ; Prospective Studies ; }, abstract = {OBJECTIVE: Hyperglycemia is an independent risk factor in hospitalized patients for adverse outcomes, even if patients are not diabetic. We used continuous glucose monitoring to evaluate whether glycemic control (hyperglycemia) in the first 72 h after an intensive care admission was associated with the need for admission to a post discharge long-term medical facility.

RESULTS: We enrolled 59 coronary artery bypass grafting patients. Poor glycemic control was defined as greater than 33% of continuous glucose monitoring values < 70 and > 180 mg/dL (group 1); and then these patients were reevaluated with a less strict definition of poor glycemic control with greater than 25% of continuous glucose values < 70 and > 180 mg/dL (group 2). In group 1 4/10 (40.0%) whose glucose was not well controlled went to an extended care post discharge facility as opposed to 6/49 (12.2%) that were well controlled. In reevaluation as group 2, 5/14 (35.7%) whose glucose was not well controlled went to an extended care post discharge facility as opposed to 5/45 (11.1%) who were well controlled. Admission to a post discharge facility was increased in patients with poor glycemic control p = 0.045 and p = 0.042 for group 1 and group 2, and with odds ratios of 4.8 (95% CI 1.0-22.5) and 4.4 (95% CI 1.0-19.4), respectively.}, } @article {pmid30064521, year = {2018}, author = {Ponce-Benavente, L and Rejas-Pinelo, P and Aguilar-Luis, MA and Palomares-Reyes, C and Becerra-Goicochea, L and Pinillos-Vilca, L and Silva-Caso, W and Costa, LE and Weilg, P and Alvitrez-Arana, J and Bazán-Mayra, J and Del Valle-Mendoza, J}, title = {Frequency and coinfection between genotypes of human papillomavirus in a population of asymptomatic women in northern Peru.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {530}, pmid = {30064521}, issn = {1756-0500}, support = {Grant: UPC-EXP-02-2017//4th research incentive of the Universidad Peruana de Ciencias Aplicadas Lima, Peru./ ; }, mesh = {Adolescent ; Adult ; *Coinfection ; Cross-Sectional Studies ; Female ; *Genotype ; Humans ; Middle Aged ; Papillomaviridae/*genetics ; Papillomavirus Infections/epidemiology/*genetics ; Peru/epidemiology ; Prevalence ; Uterine Cervical Neoplasms ; Young Adult ; }, abstract = {OBJECTIVE: Describe the prevalence of HPV genotypes via PCR and DNA sequencing in 397 women who attended to the gynecological outpatient center in the Hospital Regional Docente de Cajamarca from March to September 2017.

RESULTS: A positive PCR result for HPV was observed in 121 cervical samples. A high-risk genotype was found in 63.6% (77/121) of patients, a probably oncogenic type in 23.1% (28/121) and a low-risk type in 7.4%. Among the high-risk genotypes, HPV-31 was the most common one present in 20% (21/77), followed by HPV-16 in 11.4% (12/77). Coinfections between two or more genotypes were observed in 12 cases.}, } @article {pmid30064519, year = {2018}, author = {Fairman, KA and Peckham, AM and Rucker, ML and Rucker, JH and Sclar, DA}, title = {Use of power-law analysis to predict abuse or diversion of prescribed medications: proof-of-concept mathematical exploration.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {523}, pmid = {30064519}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; *Analgesics, Opioid ; Female ; Fentanyl ; Forecasting ; Humans ; Middle Aged ; *Models, Theoretical ; *Prescription Drug Diversion ; Substance-Related Disorders ; Young Adult ; }, abstract = {OBJECTIVE: To conduct a proof-of-concept study comparing Lorenz-curve analysis (LCA) with power-law (exponential function) analysis (PLA), by applying segmented regression modeling to 1-year prescription claims data for three medications-alprazolam, opioids, and gabapentin-to predict abuse and/or diversion using power-law zone (PLZ) classification.

RESULTS: In 1-year baseline observation, patients classified into the top PLZ groups (PLGs) were demographically and diagnostically similar to those in Lorenz-1 (top 1% of utilizers) and Lorenz-25 (top 25%). For prediction of follow-up (6-month post-baseline) Lorenz-1 use of alprazolam and opioids (i.e., potential abuse/diversion), PLA had somewhat lower sensitivity compared with LCA (83.5-95.4% vs. 99.5-99.9%, respectively) but better specificity (98.2-98.8% vs. 75.5%) and much better positive predictive value (PPV; 34.5-45.3% vs. 4.0-4.6%). Of top-PLG alprazolam- and opioid-treated patients, respectively, 20.7 and 9.9% developed incident (new) Lorenz-1 in followup, compared with < 3% of Lorenz-25 patients. For gabapentin, neither PLA nor LCA predicted incident Lorenz-1 (PPV = 0.0-1.4%). For all three medications, PLA sensitivity for follow-up hospitalization was < 5%, but specificity was better for PLA (97.3-99.2%) than for LCA (74.3-75.4%). PLA better identified patients at risk of future controlled substance abuse/diversion than did LCA, but the technique needs refinement before widespread use.}, } @article {pmid30064516, year = {2018}, author = {Geletu, AH and Teferra, AS and Sisay, MM and Teshome, DF}, title = {Incidence and predictors of chronic kidney diseases among type 2 diabetes mellitus patients at St. Paul's Hospital, Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {532}, pmid = {30064516}, issn = {1756-0500}, mesh = {Diabetes Mellitus, Type 2/*complications ; Ethiopia/epidemiology ; Female ; Follow-Up Studies ; Humans ; Incidence ; Male ; Renal Insufficiency, Chronic/*epidemiology/etiology ; Retrospective Studies ; }, abstract = {OBJECTIVE: This study aimed to estimate the incidence of chronic kidney disease and its predictors among newly diagnosed type 2 diabetes patients attending St. Paul's Hospital, Addis Ababa, Ethiopia.

RESULTS: The overall incidence of chronic kidney disease was a major public health issue among type 2 diabetes mellitus patients with 2178 (95% CI 12,801, 21,286) cases per 10,000 patient-months. Moreover, 62(14.25%) patients in the sample experienced chronic kidney disease. Old age [adjusted hazard ratio (AHR) = 1.06, 95%CI 1.03, 1.09], no diabetic retinopathy [AHR = 0.13, 95%CI 0.07-0.24], high density lipoprotein cholesterol ≥ 40 mg/dl [AHR = 0.55, 95%CI 0.31, 0.97] and high body mass index [AHR = 1.17, 95%CI 1.1, 1.25] were common factors for chronic kidney diseases.}, } @article {pmid30064508, year = {2018}, author = {Khatoon, S and Budhathoki, SS and Bam, K and Thapa, R and Bhatt, LP and Basnet, B and Jha, N}, title = {Socio-demographic characteristics and the utilization of HIV testing and counselling services among the key populations at the Bhutanese Refugees Camps in Eastern Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {535}, pmid = {30064508}, issn = {1756-0500}, mesh = {Adult ; Bhutan/ethnology ; *Counseling ; Cross-Sectional Studies ; Demography ; Female ; HIV Infections/*diagnosis ; Humans ; Male ; Nepal ; Refugees ; Young Adult ; }, abstract = {OBJECTIVES: This cross-sectional study was conducted to describe the socio-demographic characteristics, assess the utilization of HIV testing and counselling services, and to explore the reasons for the non-utilization of HIV testing and counselling services among the key populations at the Bhutanese refugee camps in eastern Nepal.

RESULTS: The HIV testing and counselling services are utilized by less than a third (29%) of the key population among the Bhutanese Refugees. The prime source of information about the HIV testing and counselling sites has been health workers followed by peer/outreach educators and neighbors. Common self-reported barriers for utilization of HIV testing and counselling services by the Bhutanese refugees were self-perceived stigma about HIV, the fear of being discriminated and the lack of knowledge about HIV testing and counselling services. There is a need to analyze the gap between availability and utilization through more qualitative approaches in order to identify interventions to increase the uptake of the HIV testing and counselling services.}, } @article {pmid30064496, year = {2018}, author = {Dos Santos, LC and de Oliveira Guimarães, L and Grazziotin, AL and de Morais, W and Cubas, ZS and de Oliveira, MJ and da Costa Vieira, RF and Biondo, AW and Kirchgatter, K}, title = {First molecular screening of Plasmodium species in ungulates from Southern Brazil.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {536}, pmid = {30064496}, issn = {1756-0500}, mesh = {Animals ; Brazil ; DNA, Protozoan ; Deer/*parasitology ; Malaria ; Plasmodium/*isolation & purification ; }, abstract = {OBJECTIVE: Despite malaria epidemiology has been extensively studied in primates, few studies were conducted in ungulates. After half a century without descriptions of Plasmodium spp. in deer since its first identification, recent research has rediscovered Plasmodium on ungulates in Africa, Asia, North America and South America, including Central Brazil. Here, a captive herd was evaluated in southern Brazil using light microscopy and PCR. DNA samples were tested for fragment amplification of two Plasmodium spp. genes: mitochondrial cytochrome b and small subunit ribosomal RNA.

RESULTS: All analyses were negative. However, the tests were performed on samples that were collected at a single time point, and parasitemia may fluctuate over the parasite's life cycle. Thus, the possibility of occult infection cannot be ruled out. Despite the negative results of all of the methods applied, it cannot be categorically stated that these animals are free from Plasmodium sp. infection. Further monitoring and/or multiple sequential sampling may improve the success rate of detecting parasites. Moreover, although this survey of Plasmodium represents the first molecular study on ungulate malaria parasites from Southern Brazil, further analysis of samples from different ungulate species is important for characterizing the epidemiology of Plasmodium of these mammals in this region.}, } @article {pmid30064490, year = {2018}, author = {Ayele, Y and Taye, H}, title = {Antibiotic utilization pattern for surgical site infection prophylaxis at Dil Chora Referral Hospital Surgical Ward, Dire Dawa, Eastern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {537}, pmid = {30064490}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Anti-Bacterial Agents/*therapeutic use ; *Antibiotic Prophylaxis ; Child ; Child, Preschool ; Cross-Sectional Studies ; Ethiopia ; Female ; Humans ; Infant ; Male ; Middle Aged ; *Practice Patterns, Physicians' ; Referral and Consultation ; Retrospective Studies ; *Surgical Wound Infection ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to assess utilization pattern of surgical antibiotic prophylaxis in surgical wards of Dil Chora Referral Hospital.

RESULTS: Prophylactic antibiotics were given in all surgical procedures. More than half of the participants 206(53.6%) were given Ceftriaxone while combination of Ceftriaxone and Metronidazole were used for 159(41.4%) patients. The most common procedure (88.3%), appendectomy, was managed with combination of Ceftriaxone and Metronidazole while the remaining was on Ceftriaxone. Hernia repair, another common procedure seen in this ward, was majorly managed by combination of Ceftriaxone and Metronidazole (60.7%) while the rest were on ceftriaxone alone. In general, inconsistence in antibiotic selection for different types of surgical procedures was seen. The surgical prophylactic antibiotics should be prescribed according to the international guidelines.}, } @article {pmid30064488, year = {2018}, author = {Mizuno, H and Taketomi, A}, title = {MicroRNA-101 inhibits the expression of Rhes, a striatal-enriched small G-protein, at the post-transcriptional level in vitro.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {528}, pmid = {30064488}, issn = {1756-0500}, mesh = {3' Untranslated Regions ; GTP-Binding Proteins/*metabolism ; Genes, ras ; HEK293 Cells ; Humans ; MicroRNAs/*physiology ; Monomeric GTP-Binding Proteins ; Neurons ; Signal Transduction ; Visual Cortex ; }, abstract = {OBJECTIVE: Ras homolog enriched in striatum (Rhes) is a small GTP-binding protein that is predominantly localized in the striatal region of the brain. Rhes affects various signaling pathways and plays important roles in Huntington's disease development caused by striatal anomalies. However, the mechanism underlying the regulation of Rhes expression is not fully understood. We hypothesized that Rhes expression might be regulated by microRNAs (miRNAs), which are small noncoding RNAs that regulate gene expression by interacting with the 3'-untranslated region (3'UTR) of mRNA. This study therefore investigated the interaction between miRNAs and the Rhes mRNA 3'UTR.

RESULTS: The results of luciferase assay showed that miR-101, the miRNA determined to have the highest possibility of interacting with the Rhes mRNA 3'UTR using DIANA-microT, significantly inhibits luciferase activity, suggesting that miR-101 directly targets the Rhes mRNA 3'UTR. Additionally, Rhes protein levels in cultured cells co-transfected with a plasmid containing the complete Rhes cDNA and miR-101 were significantly downregulated by miR-101 as demonstrated by western blot analysis. These results support our hypothesis that Rhes expression is regulated by miRNA and indicate that miR-101 may be a potent modulator of Rhes expression in striatal neurons.}, } @article {pmid30064487, year = {2018}, author = {Halawi, E and Assefa, T and Hussen, S}, title = {Pattern of antibiotics use, incidence and predictors of surgical site infections in a Tertiary Care Teaching Hospital.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {538}, pmid = {30064487}, issn = {1756-0500}, mesh = {Adult ; Anti-Bacterial Agents/*therapeutic use ; Ethiopia ; Female ; Hospitals, Teaching ; Humans ; Incidence ; Male ; Middle Aged ; *Practice Patterns, Physicians' ; *Surgical Wound Infection ; Tertiary Healthcare ; }, abstract = {OBJECTIVE: Surgical site infections (SSIs) were the most common healthcare-associated infection mainly in developing countries. Inappropriate use of surgical antibiotic prophylaxis, in terms of antibiotic choice, timing, and duration, can lead to the selection of resistant microorganisms and high costs. The aim of this study was to investigate the pattern of antibiotic use, incidence and predictors of SSIs at Tikur Anbessa Specialized Hospital, Addis Ababa, Ethiopia.

RESULTS: From 131 patients, 55.7% were male study participants. Ninety (68.7%) patients received preoperative prophylaxis. Ceftriaxone was the most 76 (84.5%) prescribed agent for prophylaxis. Twenty-seven (20.6%) patients developed surgical site infection. Previous surgery AOR = 3.22 (95% CI [1.14-9.13]) and alcohol use AOR = 7.04 (95% CI [2.56-23.12, p = 0.000]) were independent predictors of SSIs in multivariate logistic regression analysis.}, } @article {pmid30064486, year = {2018}, author = {Moura, ECR and da Cunha Leal, P and Serra, ICPB and de Paulo Ribeiro, B and do Nascimento, JR and do Nascimento, FRF and Sakata, RK}, title = {Tumor growth activity of duloxetine in Ehrlich carcinoma in mice.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {525}, pmid = {30064486}, issn = {1756-0500}, support = {305608/2015-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)/ ; }, mesh = {Animals ; Carcinoma, Ehrlich Tumor/*drug therapy ; Duloxetine Hydrochloride/*pharmacology ; Female ; Lymphocytes ; Mice ; Nitric Oxide/metabolism ; Serotonin and Noradrenaline Reuptake Inhibitors/*pharmacology ; Spleen ; }, abstract = {OBJECTIVE: The objective of this study was to analyze whether duloxetine influences tumor growth in Ehrlich carcinoma. The mice were administered 5 or 30 mg/kg of duloxetine or saline solution. All animals were inoculated with tumor cells. The tumor progression was evaluated by body weight, abdominal circumference, ascites volume and tumor cell count. The effect of duloxetine on immune response was evaluated by lymphoid cells, nitric oxide (NO) production, arginase and superoxide dismutase (SOD) activity and the spleen immunophenotyping.

RESULTS: There was no difference between the groups regarding weight, abdominal circumference, ascites volume and number of tumor cells. Duloxetine increased the cells of the inguinal lymph node. There was no difference in the number of cells in the bone marrow and spleen. Ascites SOD activity was greater in Duloxetine groups. There were no differences in the levels of NO, nitrite, and arginase. The number of antibody for CD3 (CD3+), CD4+, CD8+ and CD28+ cells was lower in the duloxetine groups. In conclusion, duloxetine has no direct effect on tumor growth and does not alter immunity. The drug increased the SOD that fights free radicals and led the migration of lymphocytes, suggesting that duloxetine could be used in tumor-bearing individuals.}, } @article {pmid30064485, year = {2018}, author = {Hashmi, AA and Aijaz, S and Mahboob, R and Khan, SM and Irfan, M and Iftikhar, N and Nisar, M and Siddiqui, M and Edhi, MM and Faridi, N and Khan, A}, title = {Clinicopathologic features of invasive metaplastic and micropapillary breast carcinoma: comparison with invasive ductal carcinoma of breast.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {531}, pmid = {30064485}, issn = {1756-0500}, mesh = {Adult ; Aged ; Breast Neoplasms/*pathology ; Carcinoma, Ductal, Breast/*pathology ; Carcinoma, Papillary/*pathology ; Female ; Humans ; *Lymphatic Metastasis ; Middle Aged ; Neoplasm Invasiveness ; }, abstract = {OBJECTIVES: The aim of this study was to determine the frequency of metaplastic breast carcinoma and invasive micropapillary carcinoma in our population and also to compare the clinico-pathologic features of metaplastic breast carcinoma and invasive micropapillary carcinoma with invasive ductal carcinoma, not otherwise specified (IDC, NOS).

RESULTS: 86.9% of the cases were identified as ductal carcinoma, NOS, while 2.2% were metaplastic and 0.76% cases were micropapillary carcinoma. Metaplastic carcinomas were found to be of higher grade as compared to IDC, NOS as 81% of metaplastic carcinoma were grade III compared to 35% IDC, NOS. 79% of metaplastic carcinoma were ER negative and 86% were PR negative, respectively as compared to ductal carcinoma NOS, which were 40% ER negative and 54% were PR. Similarly, 86.7% micropapillary cancers were ER positive and 73.3% were PR positive. Moreover, 66.7% micropapillary carcinoma showed nodal metastasis and 77.8% showed lymphovascular invasion, which was significantly higher than that of IDC, NOS micropapillary and metaplastic carcinomas accounts for less than 2 and 1% of the breast cancer burden in our population and highly correlates with poor prognosis parameters therefore, require more intensive management in our population.}, } @article {pmid30064483, year = {2018}, author = {Belachew, T and Mihret, A and Legesse, T and Million, Y and Desta, K}, title = {High level of drug resistance by gram-negative bacteria from selected sewage polluted urban rivers in Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {524}, pmid = {30064483}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents ; Drug Resistance ; *Drug Resistance, Microbial ; Escherichia coli ; Ethiopia ; Gram-Negative Bacteria/*drug effects ; Microbial Sensitivity Tests ; Rivers ; Sewage/*microbiology ; }, abstract = {OBJECTIVE: The aim of this study was to determine the level of drug resistance by gram-negative bacteria isolated from selected sewage polluted urban rivers in Addis Ababa, Ethiopia.

RESULTS: From a total of 94 river water samples, 90 medically important gram-negative bacterial isolates were recovered to the species level. The predominant bacteria isolated were E. coli. 23 (26%) followed by K. pneumoniae 18 (20%), K. oxytoca 17 (19%). E. coli showed a high level of resistance to ampicillin 21 (91.3%), cefalotin, cefuroxime, ceftriaxone and cefepime 16 (70%). Both K. pneumoniae and K. oxytoca showed high resistance to ampicillin 16 (94%) and 17 (95%) respectively. Among identified bacterial species, most of them showed a multidrug-resistant pattern. Providential retigerri showed 100% multidrug resistance followed by P. alkalificiens (90%), E. coli (78%), M. morgani (75%), and C. frundi (60%).}, } @article {pmid30064480, year = {2018}, author = {Alfaqih, MA and Bashir, N and Saadeh, R and Khader, Y and Barqawi, M and Alqudah, S}, title = {Dysregulation of the RANKL/RANK/OPG axis in thalassemia intermedia patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {534}, pmid = {30064480}, issn = {1756-0500}, support = {139/2015//Deanship of Research, Jordan University of Science and Technology/ ; }, mesh = {Biomarkers/blood ; Bone Density ; Case-Control Studies ; Child ; Erythropoietin/blood ; Female ; Humans ; Jordan ; Male ; NF-kappa B ; Osteoporosis/etiology/metabolism ; Osteoprotegerin/*metabolism ; RANK Ligand/*metabolism ; beta-Thalassemia/complications/genetics/*metabolism ; }, abstract = {OBJECTIVE: Thalassemia intermedia (TI) describes a disease ranging in severity between β thalassemia major (TM) and β thalassemia trait. Osteoporosis is observed in TI and TM. The exact reason of osteoporosis in TI could be hypogonadism and/or an increase in erythropoietin (EPO) levels. The carboxy-terminal collagen cross links (CTX), a marker of bone resorption, and the N-terminal propeptide of type 1 collagen (P1NP), a marker of bone formation are serum markers of osteoporosis. The receptor activator of NF-kappaB ligand (RANKL)/receptor activator of NF-kappaB (RANK)/osteoprotegerin (OPG) axis plays an important role in metabolic bone diseases. Herein, we tested the relationship between the RANKL/RANK/OPG axis and the bone-turnover markers CTX and P1NP in TI.

RESULTS: We recruited 44 TI patients and 33 non-thalassemic controls and measured the serum levels of hemoglobin, sex steroid hormones, CTX, P1NP, RANKL and OPG. We then used a general linear model to test the association of the above variables with CTX and P1NP as outcome variables. We showed that EPO levels were the strongest predictor of CTX change (P < 0.000), followed by RANKL (P = 0.017). On the other hand, RANKL was the strongest predictor of P1NP change (P < 0.000), followed by OPG (P = 0.009) and EPO (P = 0.024).}, } @article {pmid30064478, year = {2018}, author = {Spyroglou, II and Spöck, G and Rigas, AG and Paraskakis, EN}, title = {Evaluation of Bayesian classifiers in asthma exacerbation prediction after medication discontinuation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {522}, pmid = {30064478}, issn = {1756-0500}, mesh = {Adolescent ; *Algorithms ; Asthma/classification/*physiopathology ; *Bayes Theorem ; Child ; Child, Preschool ; Greece ; Humans ; Infant ; Probability ; }, abstract = {OBJECTIVE: The achievement of the optimal control of the disease is of cardinal importance in asthma treatment. As the control of the disease is sustained the medication should be gradually reduced and then stopped. Nevertheless, the discontinuation of asthma medication may lead to loss of disease control and eventually to an exacerbation of the disease. The goal of this paper is to examine the performance of Bayesian network classifiers in predicting asthma exacerbation based on several patient's parameters such as objective measurements and medical history data.

RESULTS: In this study several Bayesian network classifiers are presented and evaluated. It is shown that the proposed semi-naive network classifier with the use of Backward Sequential Elimination and Joining algorithm is able to predict if a patient will have an exacerbation of the disease after his last assessment with 93.84% accuracy and 90.9% sensitivity. In addition, the resulting structure and the conditional probability tables give a clear view of the probabilistic relationships between the used factors. This network may help the clinicians to identify the patients who are at high risk of having an exacerbation after stopping the medication and to confirm which factors are the most important.}, } @article {pmid30064476, year = {2018}, author = {Alba-Martínez, Z and Ramírez-Silva, L and Hernández-Alcántara, G}, title = {Exploring the differences between the three pyruvate kinase isozymes from Vibrio cholerae in a heterologous expression system.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {527}, pmid = {30064476}, issn = {1756-0500}, support = {IA204816//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; IN215918//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, mesh = {*Gene Expression ; Genes, Bacterial ; Isoenzymes ; Pyruvate Kinase/*metabolism ; Vibrio cholerae/*enzymology ; }, abstract = {OBJECTIVE: The genome of Vibrio cholerae has three paralog genes encoding for distinct pyruvate kinases. We were interested in elucidating whether they were expressed, and contributed to the pyruvate kinase activity of V. cholerae. VcIPK and VcIIPK were transformed and expressed in BL21-CodonPlus(DE3)-RIL strain, whereas VcIIIPK could not be transformed. Those studied did contribute to the pyruvate kinase activity of the bacteria. Therefore, our aim was to find an efficient transformation and commonly used over-expression heterologous system for VcIIIPK and develop its purification protocol.

RESULTS: vcIpk, vcIIpk and vcIIIpk genes were transformed in six different BL21 expression strains. No transformants were obtained for the vcIIIpk gene using BL21(DE3), BL21(DE3)pLysS and BL21(DE3)CodonPlus-RIL strains. Reduced rates of cell growth were observed for BL21-Gold(DE3)pLysS and Origami B(DE3)pLysS. High efficiency of transformation was obtained for BL21-AI. Using this strain, VcIIIPK was purified but proved to be unstable during its purification and storage. Therefore, the transformation of vcIIIpk gene resulted in a toxic, mildly toxic or nontoxic product for these BL21 strains. Despite VcIIPK and VcIIIPK being phylogenetically related, the preservation of the proteins is drastically different; whereas one is preserved during purification and storage, the other is auto-proteolyzed completely in less than a week.}, } @article {pmid30064471, year = {2018}, author = {Mendes, TA and Caramês, J and Lopes, LP and Ramalho, AL}, title = {Sphere-plane methodology to evaluate the wear of titanium of dental implants: a research proposal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {529}, pmid = {30064471}, issn = {1756-0500}, mesh = {Dental Abutments ; Dental Implant-Abutment Design ; *Dental Implants ; Dental Stress Analysis ; Materials Testing ; Research Design ; Surface Properties ; *Titanium ; }, abstract = {OBJECTIVE: Titanium is the most commonly used material to manufacture dental implants and abutments. Recently, zirconia abutments have been manufactured with better aesthetic properties. However, zirconia abutments are harder than titanium implants; therefore, they could wear the implant surface. Therefore, this article aims to describe a sphere-plane system that can be used to assess the wear that different abutment materials cause in the titanium of dental implants when submitted to cyclic loading. This method can be used to simulate the oral cavity, where the abutment (sphere) applies loads onto the implant (titanium plane). The spheres were made of different materials (titanium and zirconia), and the specimens were loaded for 4,000,000 cycles. The scar size and area on titanium planes were measured with stereoscopic images and analysed through profilometry.

RESULTS: The wear of titanium planes was similar when tested against zirconia or titanium spheres. The sphere-plane system is a method that can be used to evaluate and quantify the wear of the titanium of dental implants, and compared with methods that use real implants, this system is simpler and less expensive. This method could facilitate further research to evaluate the wear of titanium against different materials and under different testing conditions.}, } @article {pmid30064443, year = {2018}, author = {Hayter, EA and Brown, TM}, title = {Additive contributions of melanopsin and both cone types provide broadband sensitivity to mouse pupil control.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {83}, pmid = {30064443}, issn = {1741-7007}, support = {BB/I017836/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N014901/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Intrinsically photosensitive retinal ganglion cells (ipRGCs) drive an array of non-image-forming (NIF) visual responses including circadian photoentrainment and the pupil light reflex. ipRGCs integrate extrinsic (rod/cone) and intrinsic (melanopsin) photoreceptive signals, but the contribution of cones to ipRGC-dependent responses remains incompletely understood. Given recent data revealing that cone-derived colour signals influence mouse circadian timing and pupil responses in humans, here we set out to investigate the role of colour information in pupil control in mice.

RESULTS: We first recorded electrophysiological activity from the pretectal olivary nucleus (PON) of anaesthetised mice with a red-shifted cone population (Opn1mwR) and mice lacking functional cones (Cnga3-/-) or melanopsin (Opn1mwR; Opn4-/-). Using multispectral stimuli to selectively modulate the activity of individual opsin classes, we show that PON cells which receive ipRGC input also exhibit robust S- and/or L-cone opsin-driven activity. This population includes many cells where the two cone opsins drive opponent responses (most commonly excitatory/ON responses to S-opsin stimulation and inhibitory/OFF responses to L-opsin stimulation). These cone inputs reliably tracked even slow (0.025 Hz) changes in illuminance/colour under photopic conditions with melanopsin contributions becoming increasingly dominant for higher-contrast/lower temporal frequency stimuli. We also evaluated consensual pupil responses in awake animals and show that, surprisingly, this aspect of physiology is insensitive to chromatic signals originating with cones. Instead, by contrast with the situation in humans, signals from melanopsin and both cone opsins combine in a purely additive manner to drive pupil constriction in mice.

CONCLUSION: Our data reveal a key difference in the sensory control of the mouse pupil relative to another major target of ipRGCs-the circadian clock. Whereas the latter uses colour information to help estimate time of day, the mouse pupil instead sums signals across cone opsin classes to provide broadband spectral sensitivity to changes in illumination. As such, while the widespread co-occurrence of chromatic responses and melanopsin input in the PON supports a close association between colour discrimination mechanisms and NIF visual processing, our data suggest that colour opponent PON cells in the mouse contribute to functions other than pupil control.}, } @article {pmid30064421, year = {2018}, author = {Ashtiani, M and Salehzadeh-Yazdi, A and Razaghi-Moghadam, Z and Hennig, H and Wolkenhauer, O and Mirzaie, M and Jafari, M}, title = {A systematic survey of centrality measures for protein-protein interaction networks.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {80}, pmid = {30064421}, issn = {1752-0509}, abstract = {BACKGROUND: Numerous centrality measures have been introduced to identify "central" nodes in large networks. The availability of a wide range of measures for ranking influential nodes leaves the user to decide which measure may best suit the analysis of a given network. The choice of a suitable measure is furthermore complicated by the impact of the network topology on ranking influential nodes by centrality measures. To approach this problem systematically, we examined the centrality profile of nodes of yeast protein-protein interaction networks (PPINs) in order to detect which centrality measure is succeeding in predicting influential proteins. We studied how different topological network features are reflected in a large set of commonly used centrality measures.

RESULTS: We used yeast PPINs to compare 27 common of centrality measures. The measures characterize and assort influential nodes of the networks. We applied principal component analysis (PCA) and hierarchical clustering and found that the most informative measures depend on the network's topology. Interestingly, some measures had a high level of contribution in comparison to others in all PPINs, namely Latora closeness, Decay, Lin, Freeman closeness, Diffusion, Residual closeness and Average distance centralities.

CONCLUSIONS: The choice of a suitable set of centrality measures is crucial for inferring important functional properties of a network. We concluded that undertaking data reduction using unsupervised machine learning methods helps to choose appropriate variables (centrality measures). Hence, we proposed identifying the contribution proportions of the centrality measures with PCA as a prerequisite step of network analysis before inferring functional consequences, e.g., essentiality of a node.}, } @article {pmid30064383, year = {2018}, author = {Carmelo, VAO and Kogelman, LJA and Madsen, MB and Kadarmideen, HN}, title = {WISH-R- a fast and efficient tool for construction of epistatic networks for complex traits and diseases.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {277}, pmid = {30064383}, issn = {1471-2105}, support = {4184-00268//DFF-FTP/ ; 4184-00268//DFF-FTP/ ; }, abstract = {BACKGROUND: Genetic epistasis is an often-overlooked area in the study of the genomics of complex traits. Genome-wide association studies are a useful tool for revealing potential causal genetic variants, but in this context, epistasis is generally ignored. Data complexity and interpretation issues make it difficult to process and interpret epistasis. As the number of interaction grows exponentially with the number of variants, computational limitation is a bottleneck. Gene Network based strategies have been successful in integrating biological data and identifying relevant hub genes and pathways related to complex traits. In this study, epistatic interactions and network-based analysis are combined in the Weighted Interaction SNP hub (WISH) method and implemented in an efficient and easy to use R package.

RESULTS: The WISH R package (WISH-R) was developed to calculate epistatic interactions on a genome-wide level based on genomic data. It is easy to use and install, and works on regular genomic data. The package filters data based on linkage disequilibrium and calculates epistatic interaction coefficients between SNP pairs based on a parallelized efficient linear model and generalized linear model implementations. Normalized epistatic coefficients are analyzed in a network framework, alleviating multiple testing issues and integrating biological signal to identify modules and pathways related to complex traits. Functions for visualizing results and testing runtimes are also provided.

CONCLUSION: The WISH-R package is an efficient implementation for analyzing genome-wide epistasis for complex diseases and traits. It includes methods and strategies for analyzing epistasis from initial data filtering until final data interpretation. WISH offers a new way to analyze genomic data by combining epistasis and network based analysis in one method and provides options for visualizations. This alleviates many of the existing hurdles in the analysis of genomic interactions.}, } @article {pmid30064382, year = {2018}, author = {Çelen, İ and Doh, JH and Sabanayagam, CR}, title = {Effects of liquid cultivation on gene expression and phenotype of C. elegans.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {562}, pmid = {30064382}, issn = {1471-2164}, support = {P20 GM103446/GM/NIGMS NIH HHS/United States ; NNX12AR59G, NNX10AN63H, and NNX13AM08G//National Aeronautics and Space Administration/ ; }, mesh = {Animals ; Caenorhabditis elegans/genetics/*growth & development ; Caenorhabditis elegans Proteins/*genetics ; Culture Media/*chemistry ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental ; High-Throughput Nucleotide Sequencing ; Phenotype ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Liquid cultures have been commonly used in space, toxicology, and pharmacology studies of Caenorhabditis elegans. However, the knowledge about transcriptomic alterations caused by liquid cultivation remains limited. Moreover, the impact of different genotypes in rapid adaptive responses to environmental changes (e.g., liquid cultivation) is often overlooked. Here, we report the transcriptomic and phenotypic responses of laboratory N2 and the wild-isolate AB1 strains after culturing P0 worms on agar plates, F1 in liquid cultures, and F2 back on agar plates.

RESULTS: Significant variations were found in the gene expressions between the N2 and AB1 strains in response to liquid cultivation. The results demonstrated that 8-34% of the environmental change-induced transcriptional responses are transmitted to the subsequent generation. By categorizing the gene expressions for genotype, environment, and genotype-environment interactions, we identified that the genotype has a substantial impact on the adaptive responses. Functional analysis of the transcriptome showed correlation with phenotypical changes. For example, the N2 strain exhibited alterations in both phenotype and gene expressions for germline and cuticle in axenic liquid cultivation. We found transcript evidence to approximately 21% of the computationally predicted genes in C. elegans by exposing the worms to environmental changes.

CONCLUSIONS: The presented study reveals substantial differences between N2 and AB1 strains for transcriptomic and phenotypical responses to rapid environmental changes. Our data can provide standard controls for future studies for the liquid cultivation of C. elegans and enable the discovery of condition-specific genes.}, } @article {pmid30064381, year = {2018}, author = {Wu, L and Yu, J and Shen, Q and Huang, L and Wu, D and Zhang, G}, title = {Identification of microRNAs in response to aluminum stress in the roots of Tibetan wild barley and cultivated barley.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {560}, pmid = {30064381}, issn = {1471-2164}, support = {31620103912//National Natural Science Foundation of China/ ; CARS-05//China Agriculture Research System/ ; }, mesh = {Aluminum/*toxicity ; Carrier Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; Genotype ; High-Throughput Nucleotide Sequencing ; Hordeum/drug effects/*genetics/growth & development/metabolism ; MicroRNAs/chemistry/*metabolism ; Plant Roots/drug effects/genetics/growth & development/metabolism ; Sequence Analysis, RNA ; Stress, Physiological/genetics ; Tibet ; }, abstract = {BACKGROUND: Barley is relatively sensitive to Aluminum (Al) toxicity among cereal crops, but shows a wide genotypic difference in Al tolerance. The well-known Al-tolerant mechanism in barley is related to Al exclusion mediated by a citrate transporter HvAACT1 (Al-activated citrate transporter 1). A 1-kb insertion in the promoter region of HvAACT1 gene results in a dramatic increase of its expression level, which only occurs in some Al-tolerant cultivars. However, Al-tolerant Tibetan wild barley accession XZ29 did not have the 1-kb insertion.

RESULTS: We confirmed that the expression of HvAACT1 and secretion of citrate and other organic acids did not explain the difference in Al-tolerant wild barley XZ29 and Al-sensitive cultivated barley Golden Promise. To identify microRNAs (miRNAs) and their target genes responsive to Al stress in barley roots, eight small RNA libraries with two biological replicates from these two genotypes exposed to control and Al-treated conditions were constructed and submitted to deep sequencing. A total of 342 miRNAs were identified in Golden Promise and XZ29, with 296 miRNAs being commonly shared in the two genotypes. Target genes of these miRNAs were obtained through bioinformatics prediction or degradome identification. Comparative analysis detected 50 miRNAs responsive to Al stress, and some of them were found to be exclusively expressed in XZ29 and associated with Al tolerance.

CONCLUSIONS: miRNAs exclusively expressing in the wild barley were identified and found to be associated with Al stress tolerance. The current results provide a model of describing the roles of some special miRNAs associated with Al tolerance in the Tibetan wild barley.}, } @article {pmid30064374, year = {2018}, author = {Medlar, A and Holm, L}, title = {TOPAZ: asymmetric suffix array neighbourhood search for massive protein databases.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {278}, pmid = {30064374}, issn = {1471-2105}, support = {292589//Academy of Finland/ ; }, abstract = {BACKGROUND: Protein homology search is an important, yet time-consuming, step in everything from protein annotation to metagenomics. Its application, however, has become increasingly challenging, due to the exponential growth of protein databases. In order to perform homology search at the required scale, many methods have been proposed as alternatives to BLAST that make an explicit trade-off between sensitivity and speed. One such method, SANSparallel, uses a parallel implementation of the suffix array neighbourhood search (SANS) technique to achieve high speed and provides several modes to allow for greater sensitivity at the expense of performance.

RESULTS: We present a new approach called asymmetric SANS together with scored seeds and an alternative suffix array ordering scheme called optimal substitution ordering. These techniques dramatically improve both the sensitivity and speed of the SANS approach. Our implementation, TOPAZ, is one of the top performing methods in terms of speed, sensitivity and scalability. In our benchmark, searching UniProtKB for homologous proteins to the Dickeya solani proteome, TOPAZ took less than 3 minutes to achieve a sensitivity of 0.84 compared to BLAST.

CONCLUSIONS: Despite the trade-off homology search methods have to make between sensitivity and speed, TOPAZ stands out as one of the most sensitive and highest performance methods currently available.}, } @article {pmid30064372, year = {2018}, author = {Lu, R and Wang, Y and Xu, X and Xie, S and Wang, Y and Zhong, A and Zheng, H and Yu, Y and Gao, X and Guo, L}, title = {Establishment of a detection assay for DNA endonuclease activity and its application in the screening and prognosis of malignant lymphoma.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {6}, pmid = {30064372}, issn = {1471-2091}, support = {NSF-81572552//National Natural Science Foundation of China/International ; NSF-81772774//National Natural Science Foundation of China/International ; NSF-81772808//National Natural Science Foundation of China/International ; KW17411963500//Shanghai Science and Technology Committee Sponsorship/International ; SHDC22014002//Shanghai Hospital Development Center/International ; }, mesh = {Biomarkers, Tumor/*metabolism ; Deoxyribonuclease I/*metabolism ; Early Detection of Cancer ; Electrophoresis, Agar Gel ; *Enzyme Assays ; Female ; Humans ; Kaplan-Meier Estimate ; Lymphoma/blood/*diagnosis/*pathology ; Male ; Middle Aged ; Neoplasm Metastasis ; Plasmids ; Prognosis ; }, abstract = {BACKGROUND: Endonucleases play critical roles in maintaining genomic stability and regulating cell growth. The purpose of this study was to evaluate detection of endonuclease activity as an indicator in the early diagnosis and prognosis of lymphoma.

RESULTS: The method of endonuclease activity determination was successfully established and applied to compare cancer patient and control cohorts. Endonuclease activities of cancer tissues were significantly higher than those of adjacent control tissues (P < 0.001). We next investigated endonuclease activity in peripheral blood of enrolled patients and the controls, which were also significantly higher in patients than in controls (P = 0.015). Additionally, endonuclease activities were elevated in the metastasis subgroup compared with the non-metastasis subgroup(P = 0.038), whereas no significant difference was found between age(≤ 56y, > 56y) and gender (P = 0.736 > 0.05 and P = 0.635 > 0.05, respectively). Although there was no significant difference between control group with the non-metastatic cancer patients (P = 0.800 > 0.05), endonuclease activities were lower in the control group compared with the non-metastatic cancer patients with lymphoma (P = 0.033). The progression-free survival probability of patients with elevated R ratios(R ratio ≥ 1.4) was significantly lower than that of patients with lower R ratios (R ratio < 1.4).

CONCLUSIONS: An assay was established to detect the endonuclease activity,which might be useful for the prognosis of cancers, especially lymphoma.}, } @article {pmid30064364, year = {2018}, author = {Shinotsuka, N and Yamaguchi, Y and Nakazato, K and Matsumoto, Y and Mochizuki, A and Miura, M}, title = {Caspases and matrix metalloproteases facilitate collective behavior of non-neural ectoderm after hindbrain neuropore closure.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {17}, pmid = {30064364}, issn = {1471-213X}, support = {26110005//Japan Society for the Promotion of Science/International ; 24116704//Japan Society for the Promotion of Science/International ; 23229001//Japan Society for the Promotion of Science/International ; 16H06385//Japan Society for the Promotion of Science/International ; JP17gm0610004//Japan Agency for Medical Research and Development/International ; JP18gm5010001//Japan Agency for Medical Research and Development/International ; }, abstract = {BACKGROUND: Mammalian brain is formed through neural tube closure (NTC), wherein both ridges of opposing neural folds are fused in the midline and remodeled in the roof plate of the neural tube and overlying non-neural ectodermal layer. Apoptosis is widely observed from the beginning of NTC at the neural ridges and is crucial for the proper progression of NTC, but its role after the closure remains less clear.

RESULTS: Here, we conducted live-imaging analysis of the mid-hindbrain neuropore (MHNP) closure and revealed unexpected collective behavior of cells surrounding the MHNP. The cells first gathered to the closing point and subsequently relocated as if they were released from the point. Inhibition of caspases or matrix metalloproteases with chemical inhibitors impaired the cell relocation.

CONCLUSIONS: These lines of evidence suggest that apoptosis-mediated degradation of extracellular matrix might facilitate the final process of neuropore closure.}, } @article {pmid30064362, year = {2018}, author = {Stansfield, JC and Cresswell, KG and Vladimirov, VI and Dozmorov, MG}, title = {HiCcompare: an R-package for joint normalization and comparison of HI-C datasets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {279}, pmid = {30064362}, issn = {1471-2105}, support = {IRG-14-192-40//American Cancer Society/ ; T32ES007334//National Institute of Environmental Health Sciences/ ; }, abstract = {BACKGROUND: Changes in spatial chromatin interactions are now emerging as a unifying mechanism orchestrating the regulation of gene expression. Hi-C sequencing technology allows insight into chromatin interactions on a genome-wide scale. However, Hi-C data contains many DNA sequence- and technology-driven biases. These biases prevent effective comparison of chromatin interactions aimed at identifying genomic regions differentially interacting between, e.g., disease-normal states or different cell types. Several methods have been developed for normalizing individual Hi-C datasets. However, they fail to account for biases between two or more Hi-C datasets, hindering comparative analysis of chromatin interactions.

RESULTS: We developed a simple and effective method, HiCcompare, for the joint normalization and differential analysis of multiple Hi-C datasets. The method introduces a distance-centric analysis and visualization of the differences between two Hi-C datasets on a single plot that allows for a data-driven normalization of biases using locally weighted linear regression (loess). HiCcompare outperforms methods for normalizing individual Hi-C datasets and methods for differential analysis (diffHiC, FIND) in detecting a priori known chromatin interaction differences while preserving the detection of genomic structures, such as A/B compartments.

CONCLUSIONS: HiCcompare is able to remove between-dataset bias present in Hi-C matrices. It also provides a user-friendly tool to allow the scientific community to perform direct comparisons between the growing number of pre-processed Hi-C datasets available at online repositories. HiCcompare is freely available as a Bioconductor R package https://bioconductor.org/packages/HiCcompare/ .}, } @article {pmid30064361, year = {2018}, author = {Jung, M and Shim, S and Im, YB and Park, WB and Yoo, HS}, title = {Global gene-expression profiles of intracellular survival of the BruAb2_1031 gene mutated Brucella abortus in professional phagocytes, RAW 264.7 cells.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {82}, pmid = {30064361}, issn = {1471-2180}, abstract = {BACKGROUND: Since recognizing the interaction between Brucella and host cells is crucial to the elucidation of the infectious process, Brucella researches have prioritized the investigation of genes related to pathogenicity. To demonstrate the roles of Brucella genes, RAW 264.7 cells were infected with the Brucella abortus wild-type and mutant strains (generated using transposon mutagenesis), after which the different transcriptional responses of the infected cells were determined using microarray.

RESULTS: Following infection, enhanced strategies for intracellular survival, such as down-regulation of genes associated with cytokine responses and apoptosis, were observed in RAW 264.7 cells infected with C3 mutant strain when compared to the transcriptional responses of wild-type infected cells. Using sequence analysis, we determined the mutation site of a C3 mutant strain as the ATP-binding cassette transporter permease (BruAb2_1031). These results were evidenced by an increased level of intracellular survival of the C3 mutant strain.

CONCLUSIONS: Characteristics of each mutant strain including bacterial growth rate, abilities to induce cytokine production in macrophages after infection, internalization, and levels of intracellular survival and replication, were investigated by performing RAW 264.7 cell infection experiments. Our results indicate that the BruAb2_1031 gene might be closely related with intracellular survival of B. abortus in RAW 264.7 cells.}, } @article {pmid30064359, year = {2018}, author = {Kessi, J and Hörtensteiner, S}, title = {Inhibition of bacteriochlorophyll biosynthesis in the purple phototrophic bacteria Rhodospirillumrubrum and Rhodobacter capsulatus grown in the presence of a toxic concentration of selenite.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {81}, pmid = {30064359}, issn = {1471-2180}, abstract = {Background In many works, the chemical composition of bacterially-produced elemental selenium nanoparticles (Se0-nanoparticles) was investigated using electron dispersive X-ray analysis. The results suggest that these particles should be associated with organic compounds. However, a complete analysis of their chemical composition is still missing. Aiming at identifying organic compounds associated with the Se0-nanoparticles produced by the purple phototrophic bacteria Rhodospirillum rubrum and Rhodobacter capsulatus (α group of the proteobacteria), we used MALDI-TOF spectrometry.Results This technic revealed that numerous signals obtained from particles produced by both species of bacteria were from metabolites of the photosynthetic system. Furthermore, not only bacteriochlorophyll a, bacteriopheophytin a, and bacteriopheophorbide a, which are known to accumulate in stationary phase cultures of these bacteria grown phototrophically in the absence of selenite, were identified. The particles were also associated with intermediary metabolites of the bacteriochlorophyll a biosynthesis pathway such as protoporphyrin IX, protoporphyrin IX monomethyl ester, bacteriochlorophyllide a and, most likely, Mg-protoporphyrin IX-monomethyl ester, as well as with oxidation products of the substrates of protochlorophyllide reductase and chlorin reductase.Conclusion Accumulation of intermediary metabolites of the bacteriochlorophyll biosynthesis pathway in these purple phototrophic bacteria was attributed to inhibition of oxygen-sensitive enzymes involved in this pathway. Consistent with this interpretation it has been reported that these bacteria reduce selenite intracellularly, that they contain high levels of glutathione and that the reduction of selenite with glutathione is a very fast reaction accompanied by the production of reactive oxygen species. As many enzymes involved in the biosynthesis of bacteriochlorophyll contain [Fe-S] clusters in their active site, which are known to be degraded in the presence of reactive oxygen species as well as in the presence of molecular oxygen, we concluded that the substrates of these enzymes accumulate in cells during selenite reduction.Association of metabolites of bacteriochlorophyll biosynthesis and degradation with the Se0-nanoparticles produced by Rhodospirillum rubrum and Rhodobacter capsulatus is proposed to result from coating of the nanoparticles with the intracytoplasmic membrane of these bacteria, where the photochemical apparatus is concentrated.}, } @article {pmid30064355, year = {2018}, author = {Tan, MK and El-Bouhssini, M and Wildman, O and Tadesse, W and Chambers, G and Luo, S and Emebiri, L}, title = {Development of SNP assays for hessian fly response genes, Hfr-1 and Hfr-2, for marker-assisted selection in wheat breeding.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {50}, pmid = {30064355}, issn = {1471-2156}, support = {DAN00174//Grains Research and Development Corporation/ ; }, abstract = {BACKGROUND: The Hessian fly response genes, Hfr-1 and Hfr-2, have been reported to be significantly induced in a Hessian fly attack. Nothing is known about the allelic variants of these two genes in susceptible (S) and resistant (R) wheat cultivars.

RESULTS: Basic local alignment search tool (BLAST) analysis of Hessian fly response genes have identified three alleles of Hessian fly response gene 1 (Hfr-1) on chromosome 4AL and 7DS, and 10 alleles of Hessian fly response gene 2 (Hfr-2) on chromosome 2BS, 2DL, 4BS, 4BL, 5AL and 5BL. Resequencing exons of Hfr-1 and Hfr-2 have identified a single nucleotide polymorphism (SNP) in the lectin domain of each gene that segregates some R sources from S cultivars. Two SNP assays have been developed. The SNP883_Hfr-1 assay characterizes a 'G/A' SNP in Hfr-1, which differentiates 14 Hessian fly R cultivars from S ones. The SNP1294_Hfr-2 assay differentiates 12 R cultivars from S ones. Each of the two SNPs identified in Hfr-1 and Hfr-2 is 'G/A' and resulted in an amino acid change from isoleucine to valine in the lectin domain of the proteins of the alleles in the R cultivars. In addition to the genotype profiles of Hfr-1 and Hfr-2, generated for a set of 249 wheat cultivars which included a set of 39 R cultivars, this study has genotyped the Hessian fly response gene, HfrDrd, and the H32 gene for the wheat germplasm. Resistant cultivars from different origins with one, two, three or four resistance (R) genes in various combinations/permutations have been identified.

CONCLUSION: This study has identified allelic differences in two Hessian fly response genes, Hfr-1 and Hfr-2, between S and R cultivars and developed one SNP assay for each of the genes. These two SNP assays for Hfr-1 and Hfr-2, together with the published assays for HfrDrd and the H32 gene, can be used for the selection and incorporation of one or more of these 4 R genes identified in the different R sources in wheat breeding programs.}, } @article {pmid30064354, year = {2018}, author = {Sannemann, W and Lisker, A and Maurer, A and Léon, J and Kazman, E and Cöster, H and Holzapfel, J and Kempf, H and Korzun, V and Ebmeyer, E and Pillen, K}, title = {Adaptive selection of founder segments and epistatic control of plant height in the MAGIC winter wheat population WM-800.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {559}, pmid = {30064354}, issn = {1471-2164}, support = {28-1-46.010-13//BMEL/ ; }, mesh = {Crosses, Genetic ; *Epistasis, Genetic ; Founder Effect ; *Gene Expression Regulation, Plant ; Gene Frequency ; Genome-Wide Association Study ; Linkage Disequilibrium ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Triticum/anatomy & histology/*genetics ; }, abstract = {BACKGROUND: Multi-parent advanced generation intercross (MAGIC) populations are a newly established tool to dissect quantitative traits. We developed the high resolution MAGIC wheat population WM-800, consisting of 910 F4:6 lines derived from intercrossing eight recently released European winter wheat cultivars.

RESULTS: Genotyping WM-800 with 7849 SNPs revealed a low mean genetic similarity of 59.7% between MAGIC lines. WM-800 harbours distinct genomic regions exposed to segregation distortion. These are mainly located on chromosomes 2 to 6 of the wheat B genome where founder specific DNA segments were positively or negatively selected. This suggests adaptive selection of individual founder alleles during population development. The application of a genome-wide association study identified 14 quantitative trait loci (QTL) controlling plant height in WM-800, including the known semi-dwarf genes Rht-B1 and Rht-D1 and a potentially novel QTL on chromosome 5A. Additionally, epistatic effects controlled plant height. For example, two loci on chromosomes 2B and 7B gave rise to an additive epistatic effect of 13.7 cm.

CONCLUSION: The present study demonstrates that plant height in the MAGIC-WHEAT population WM-800 is mainly determined by large-effect QTL and di-genic epistatic interactions. As a proof of concept, our study confirms that WM-800 is a valuable tool to dissect the genetic architecture of important agronomic traits.}, } @article {pmid30064353, year = {2018}, author = {Pranzatelli, TJF and Michael, DG and Chiorini, JA}, title = {ATAC2GRN: optimized ATAC-seq and DNase1-seq pipelines for rapid and accurate genome regulatory network inference.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {563}, pmid = {30064353}, issn = {1471-2164}, support = {Intramural//National Institute of Dental and Craniofacial Research (US)/ ; }, mesh = {Chromatin Immunoprecipitation ; Computational Biology/*methods ; Deoxyribonuclease I/*metabolism ; Genomic Library ; High-Throughput Nucleotide Sequencing ; Reproducibility of Results ; Sequence Analysis, DNA/*methods ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: Chromatin accessibility profiling assays such as ATAC-seq and DNase1-seq offer the opportunity to rapidly characterize the regulatory state of the genome at a single nucleotide resolution. Optimization of molecular protocols has enabled the molecular biologist to produce next-generation sequencing libraries in several hours, leaving the analysis of sequencing data as the primary obstacle to wide-scale deployment of accessibility profiling assays. To address this obstacle we have developed an optimized and efficient pipeline for the analysis of ATAC-seq and DNase1-seq data.

RESULTS: We executed a multi-dimensional grid-search on the NIH Biowulf supercomputing cluster to assess the impact of parameter selection on biological reproducibility and ChIP-seq recovery by analyzing 4560 pipeline configurations. Our analysis improved ChIP-seq recovery by 15% for ATAC-seq and 3% for DNase1-seq and determined that PCR duplicate removal improves biological reproducibility by 36% without significant costs in footprinting transcription factors. Our analyses of down sampled reads identified a point of diminishing returns for increased library sequencing depth, with 95% of the ChIP-seq data of a 200 million read footprinting library recovered by 160 million reads.

CONCLUSIONS: We present optimized ATAC-seq and DNase-seq pipelines in both Snakemake and bash formats as well as optimal sequencing depths for ATAC-seq and DNase-seq projects. The optimized ATAC-seq and DNase1-seq analysis pipelines, parameters, and ground-truth ChIP-seq datasets have been made available for deployment and future algorithmic profiling.}, } @article {pmid30064352, year = {2018}, author = {Medvecky, M and Cejkova, D and Polansky, O and Karasova, D and Kubasova, T and Cizek, A and Rychlik, I}, title = {Whole genome sequencing and function prediction of 133 gut anaerobes isolated from chicken caecum in pure cultures.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {561}, pmid = {30064352}, issn = {1471-2164}, support = {RO0517//Czech Ministry of Agriculture/ ; CZ.1.05/2.1.00/01.0006-ED0006/01/01//Czech Ministry of Education/ ; QJ1310019//Czech Ministry of Education/ ; LQ1601//Czech Ministry of Education/ ; 15-11688S//Grantová Agentura České Republiky/ ; }, mesh = {Animals ; Bacteria, Anaerobic/genetics/*isolation & purification ; Cecum/*microbiology ; *Chickens ; DNA, Bacterial/*genetics ; Gastrointestinal Microbiome ; Genome Size ; High-Throughput Nucleotide Sequencing ; Phylogeny ; Whole Genome Sequencing/*methods ; }, abstract = {BACKGROUND: In order to start to understand the function of individual members of gut microbiota, we cultured, sequenced and analysed bacterial anaerobes from chicken caecum.

RESULTS: Altogether 204 isolates from chicken caecum were obtained in pure cultures using Wilkins-Chalgren anaerobe agar and anaerobic growth conditions. Genomes of all the isolates were determined using the NextSeq platform and subjected to bioinformatic analysis. Among 204 sequenced isolates we identified 133 different strains belonging to seven different phyla - Firmicutes, Bacteroidetes, Actinobacteria, Proteobacteria, Verrucomicrobia, Elusimicrobia and Synergistetes. Genome sizes ranged from 1.51 Mb in Elusimicrobium minutum to 6.70 Mb in Bacteroides ovatus. Clustering based on the presence of protein coding genes showed that isolates from phyla Proteobacteria, Verrucomicrobia, Elusimicrobia and Synergistetes did not cluster with the remaining isolates. Firmicutes split into families Lactobacillaceae, Enterococcaceae, Veillonellaceae and order Clostridiales from which the Clostridium perfringens isolates formed a distinct sub-cluster. All Bacteroidetes isolates formed a separate cluster showing similar genetic composition in all isolates but distinct from the rest of the gut anaerobes. The majority of Actinobacteria clustered closely together except for the representatives of genus Gordonibacter showing that the genome of this genus differs from the rest of Actinobacteria sequenced in this study. Representatives of Bacteroidetes commonly encoded proteins (collagenase, hemagglutinin, hemolysin, hyaluronidase, heparinases, chondroitinase, mucin-desulfating sulfatase or glutamate decarboxylase) that may enable them to interact with their host. Aerotolerance was recorded in Akkermansia and Cloacibacillus and was also common among representatives of Bacteroidetes. On the other hand, Elusimicrobium and the majority of Clostridiales were highly sensitive to air exposure despite their potential for spore formation.

CONCLUSIONS: Major gut microbiota members utilise different strategies for gut colonisation. High oxygen sensitivity of Firmicutes may explain their commonly reported decrease after oxidative burst during gut inflammation.}, } @article {pmid30064134, year = {2018}, author = {Paris, F and Boulahtouf, A and Kalfa, N and Guibal, MP and Gaspari, L and Servant, N and Bourguet, W and Sultan, C and Balaguer, P}, title = {Functional and Structural Study of the Amino Acid Substitution in a Novel Familial Androgen Receptor Mutation (W752G) Responsible for Complete Androgen Insensitivity Syndrome.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000491114}, pmid = {30064134}, issn = {1661-5433}, abstract = {Mutations of the androgen receptor (AR) gene are the most frequent cause of 46,XY disorders of sex development. They are associated with a variety of phenotypes, ranging from phenotypic women (complete androgen insensitivity syndrome, CAIS) to milder degrees of undervirilization (partial forms) or men with only infertility (mild form). We identified a new W752G AR mutation responsible for a familial case of CAIS and performed an in vitro study and structural analysis of this mutation and the only other reported substitution affecting the same amino acid (W752R). Although sex assignment is not discussed in cases of CAIS, we show how the phenotype-genotype correlation can be refined by in vitro and structural studies according to the nature of the amino acid substitution, which in turn may have interesting impacts on the follow-up of these patients.}, } @article {pmid30063997, year = {2018}, author = {Carlsen, MM and Fér, T and Schmickl, R and Leong-Škorničková, J and Newman, M and Kress, WJ}, title = {Resolving the rapid plant radiation of early diverging lineages in the tropical Zingiberales: Pushing the limits of genomic data.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {55-68}, doi = {10.1016/j.ympev.2018.07.020}, pmid = {30063997}, issn = {1095-9513}, abstract = {Many cases of rapid evolutionary radiations in plant and animal lineages are known; however phylogenetic relationships among these lineages have been difficult to resolve by systematists. Increasing amounts of genomic data have been sequentially applied in an attempt to resolve these radiations, dissecting their evolutionary patterns into a series of bifurcating events. Here we explore one such rapid radiation in the tropical plant order Zingiberales (the bananas and relatives) which includes eight families, approximately 110 genera, and more than 2600 species. One clade, the "Ginger families", including (Costaceae + Zingiberaceae) (Marantaceae + Cannaceae), has been well-resolved and well-supported in all previous studies. However, well-supported reconstructions among the "Banana families" (Musaceae, Heliconiaceae, Lowiaceae, Strelitziaceae), which most likely diverged about 90 Mya, have been difficult to confirm. Supported with anatomical, morphological, single locus, and genome-wide data, nearly every possible phylogenetic placement has been proposed for these families. In an attempt to resolve this complex evolutionary event, hybridization-based target enrichment was used to obtain sequences from up to 378 putatively orthologous low-copy nuclear genes (all ≥ 960 bp). Individual gene trees recovered multiple topologies among the early divergent lineages, with varying levels of support for these relationships. One topology of the "Banana families" (Musaceae (Heliconiaceae (Lowiaceae + Strelitziaceae))), which has not been suggested until now, was almost consistently recovered in all multilocus analyses of the nuclear dataset (concatenated - ExaML, coalescent - ASTRAL and ASTRID, supertree - MRL, and Bayesian concordance - BUCKy). Nevertheless, the multiple topologies recovered among these lineages suggest that even large amounts of genomic data might not be able to fully resolve relationships at this phylogenetic depth. This lack of well-supported resolution could suggest methodological problems (i.e., violation of model assumptions in both concatenated and coalescent analyses) or more likely reflect an evolutionary history shaped by an explosive, rapid, and nearly simultaneous polychotomous radiation in this group of plants towards the end of the Cretaceous, perhaps driven by vertebrate pollinator selection.}, } @article {pmid30063881, year = {2018}, author = {Newman, EA and Wu, D and Taketo, MM and Zhang, J and Blackshaw, S}, title = {Canonical Wnt signaling regulates patterning, differentiation and nucleogenesis in mouse hypothalamus and prethalamus.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {236-248}, pmid = {30063881}, issn = {1095-564X}, support = {R01 DK108230/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/physiology ; Cell Differentiation/physiology ; Female ; Hypothalamus/cytology/*embryology/*metabolism ; Male ; Mice ; Mice, Transgenic ; Pregnancy ; Wnt Signaling Pathway/*physiology ; beta Catenin/genetics/metabolism ; }, abstract = {The hypothalamus is a small, but anatomically and functionally complex region of the brain whose development is poorly understood. In this study, we have explored its development by studying the canonical Wnt signaling pathway, generating gain and loss of function mutations of beta-catenin (Ctnnb1) in both hypothalamic and prethalamic neuroepithelium. Deletion of Ctnnb1 resulted in an anteriorized and hypoplastic hypothalamus. Posterior structures were lost or reduced, and anterior structures were expanded. In contrast, overexpression of a constitutively active mutant form of Ctnnb1 resulted in severe hyperplasia of prethalamus and hypothalamus, and expanded expression of a subset of posterior and premamillary hypothalamic markers. Moderate defects in differentiation of Arx-positive GABAergic neural precursors were observed in both prethalamus and hypothalamus of Ctnnb1 loss of function mutants, while in gain of function mutants, their differentiation was completely suppressed, although markers of prethalamic progenitors were preserved. Multiple other region-specific markers, including several specific posterior hypothalamic structures, were also suppressed in Ctnnb1 gain of function mutations. Severe, region-specific defects in hypothalamic nucleogenesis were also observed in both gain and loss of function mutations of Ctnnb1. Finally, both gain and loss of function of Ctnnb1 also produced severe, non-cell autonomous disruptions of pituitary development. These findings demonstrate a central and multifaceted role for canonical Wnt signaling in regulating growth, patterning, differentiation and nucleogenesis in multiple diencephalic regions.}, } @article {pmid30063204, year = {2018}, author = {Ma, K and Yin, Q and Chen, L and Lai, Q and Xu, Y}, title = {Bacillus acanthi sp. nov., isolated from the rhizosphere soil of a mangrove plant Acanthus ilicifolius.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3047-3051}, doi = {10.1099/ijsem.0.002950}, pmid = {30063204}, issn = {1466-5034}, mesh = {Acanthaceae/*microbiology ; Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hong Kong ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel bacterium, designated strain L28T, was isolated from the rhizosphere soil of a mangrove plant in Hong Kong. Cells of strain L28T are Gram-stain-positive, rod-shaped and endospore-forming. Optimum growth occurs at 37 °C (range, 20-45 °C), 0.5 % (w/v) NaCl (range, 0-5.0 %) and pH 7.5 (range, 6.5-9.0). The major fatty acids are iso-C15 : 0 and C16 : 1ω7c alcohol. The major respiratory quinone is MK-7. The polar lipid profile comprises phospholipid, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol and two unidentified lipids. The 16S rRNA gene sequence analyses indicated that strain L28T exhibited the highest similarity of 96.7 % to Bacillus asahii MA001T. The genome size of strain L28T was 4 063 863 bp with a 36.9 mol% DNA G+C content. Based on the phenotypic and chemotaxonomic properties, along with the phylogenic distinctiveness, it was concluded that this strain represents a novel species of the genus Bacillus, for which the name Bacillusacanthi sp. nov. is proposed. The type strain of this novel species is L28T (=DSM 104296T=MCCC 1K03287T).}, } @article {pmid30063203, year = {2018}, author = {Mu, S and Sun, T and Li, Y and Jiang, S and Guo, X and Wang, X and Zhao, J and Xiang, W}, title = {Glycomyces dulcitolivorans sp. nov., isolated from rhizosphere soil of wheat (Triticum aestivum L.).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3034-3039}, doi = {10.1099/ijsem.0.002948}, pmid = {30063203}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Triticum/*microbiology ; Vitamin K 2/chemistry ; }, abstract = {A novel actinomycete, designated strain SJ-25T, was isolated from rhizosphere soil of wheat (Triticumaestivum L.) and characterized using a polyphasic approach. 16S rRNA gene sequence analysis indicated that strain SJ-25T belonged to the genus Glycomyces and was closely related to Glycomyces scopariae YIM 56256T (99.0 % 16S rRNA gene sequence similarity), Glycomyces artemisiae IXS4T (98.8 %), Glycomyces sambucus E71T (98.7 %) and Glycomyces mayteni YIM 61331T (98.4 %). Moreover, key morphological and chemotaxonomic properties also confirmed the affiliation of strain SJ-25T to the genus Glycomyces. The cell wall contained meso-diaminopimelic acid and the whole-cell hydrolysates contained galactose, glucose and xylose. The phospholipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol mannoside, glycolipid and two unidentified polar lipids. The menaquinones were MK-11, MK-10(H4) and MK-10(H2). Major fatty acids were iso-C16 : 0, anteiso-C15 : 0, iso-C15 : 0, anteiso-C17 : 0 and iso-C14 : 0. The DNA G+C content was 72.2 mol%. The combination of DNA-DNA hybridization results and some phenotypic characteristics demonstrated that strain SJ-25T could be distinguished from its closely related strains. Therefore, it is proposed that strain SJ-25T represents a novel species of the genus Glycomyces, for which the name Glycomycesdulcitolivorans sp. nov. is proposed. The type strain is SJ-25T (=CGMCC 4.7414T=DSM 105121T).}, } @article {pmid30063201, year = {2018}, author = {Lee, Y and Jeon, CO}, title = {Kaistia algarum sp. nov., isolated from a freshwater green alga Paulinella chromatophora.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3028-3033}, doi = {10.1099/ijsem.0.002943}, pmid = {30063201}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chlorophyta/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhizobiaceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-negative, strictly aerobic, non-motile and short rod- or coccus-shaped bacterium, designated strain LYH11T, was isolated from a freshwater green alga Paulinella chromatophora. The strain grew at 5-37 °C (optimum, 30 °C) and pH 6-9 (pH 7) and in the presence of 0-1 % (w/v) NaCl (optimum, 0 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain LYH11T clearly belonged to the genus Kaistia of the family Rhizobiaceae. Strain LYH11T shared the highest 16S rRNA gene sequence similarity to Kaistia soli 5YN9-8T (98.3 %), Kaistia terrae 5YN3-3T (98.2 %), Kaistia geumhonensis B1-1T (97.8 %), Kaistia defluvii B6-12T (97.4 %) and Kaistia granuli Ko04T (97.2 %). The average nucleotide identity and in silico DNA-DNA hybridization values between strain LYH11T and K. soli 5YN9-8T, the closest Kaistia type strain, were 77.3 and 21.1 %, respectively. Major cellular fatty acids of strain LYH11T were cyclo-C19 : 0ω8c, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), iso-C10 : 0, iso-C17 : 0 3-OH, iso-C17 : 1ω5c and C18 : 0. Strain LYH11T contained phosphatidylglycerol, phosphatidylethanolamine, an unidentified phosphoaminolipid, an unidentified aminolipid, three unidentified phospholipids and five unidentified lipids as polar lipids. Ubiquinone-10 was the major respiratory quinone. The genomic DNA G+C content was 64.5 mol%. Based on the genotypic, chemotaxonomic and phenotypic analyses, strain LYH11T represents a novel species of the genus Kaistia, for which the name Kaistia algarum sp. nov. is proposed. The type strain is LYH11T (=KACC 19096T=JCM 31803T).}, } @article {pmid30063200, year = {2018}, author = {Malisorn, K and Kanchanasin, P and Phongsopitanun, W and Tanasupawat, S}, title = {Actinomadura rhizosphaerae sp. nov., isolated from rhizosphere soil of the plant Azadirachta indica.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3012-3016}, doi = {10.1099/ijsem.0.002940}, pmid = {30063200}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Azadirachta/*microbiology ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Muramic Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, strain SDA37T, belonging to the genus Actinomadura, was isolated from rhizosphere soil collected from Udon Thani Province, Thailand. The taxonomic position of the strain was characterized using a polyphasic approach. Meso-diaminopimelic acid, glucose, ribose, galactose and madurose were detected in cell-wall and whole-cell hydrolysates. The N-acyl type of muramic acid was acetyl. Menaquinones were MK-9(H6), MK-9(H8) and MK-9(H4). The predominant cellular fatty acids were iso-C16 : 0, C16 : 0, 10-methyl C18 : 0 and iso-C14 : 0. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylinositol. blast analysis of the almost-complete 16S rRNA gene sequence showed 98.8 % similarity to Actinomadura oligospora NBRC 104149T, 98.7 % similarity to Actinomadura gamaensis DSM 100815T and 97.2 % similarity to Actinomadura rupiterrae KCTC 19559T. The DNA G+C content was 73.1 mol%. Strain SDA37T showed low DNA-DNA relatedness (44.3±7.3 to 58.5±8.7 %) to A. oligospora NBRC 104149T, Actinomadura gamaensis DSM 100815T and Actinomadura rupiterrae KCTC 19559T. The new strain could also be distinguished from its closely related strains by the differences in the phenotypic characteristics. The results of taxonomic analysis suggested that strain SDA37T represented a novel species of the genus Actinomadura for which the name Actinomadura rhizosphaerae sp. nov. is proposed. The type strain is SDA37T (=KCTC 39965T=NBRC 112909T=TISTR 2523T).}, } @article {pmid30063199, year = {2018}, author = {Sannazzaro, AI and Torres Tejerizo, G and Fontana, MF and Cumpa Velásquez, LM and Hansen, LH and Pistorio, M and Estrella, MJ}, title = {Mesorhizobium sanjuanii sp. nov., isolated from nodules of Lotus tenuis in the saline-alkaline lowlands of Flooding Pampa, Argentina.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2936-2942}, doi = {10.1099/ijsem.0.002924}, pmid = {30063199}, issn = {1466-5034}, mesh = {Argentina ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lotus/*microbiology ; Mesorhizobium/*classification/genetics/isolation & purification ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/*microbiology ; Sequence Analysis, DNA ; }, abstract = {Two rhizobial strains, BSA136T and BSA150, related to the genus Mesorhizobium were isolated from root nodules of Lotus tenuis grown in saline-alkaline lowlands soil from Argentina. These strains showed different repetitive element palindromic PCR fingerprinting patterns but shared more than 99 % sequence similarity for both 16S rRNA and recA genes. Despite the symbiotic nodC gene sequences of our strains being related to the canonical Lotus biovar species comprising Mesorhizobium loti and Mesorhizobium japonicum, the 16S rRNA phylogenetic marker suggests that their taxonomical identities are closely related to Mesorhizobium helmanticense, Mesorhizobium metallidurans, Mesorhizobium thianshanense, Mesorhizobium gobiense and Mesorhizobium tarimense. Multilocus sequence analysis performed with seven housekeeping genes confirmed that BSA136T belongs to a separate clade within the genus Mesorhizobium. The results of comparisons for in silico DNA-DNA hybridization and average nucleotide identity indexes between the genomes of BSA136T and closest-related Mesorhizobium species were below the threshold for species delineation. Phenotypic features differentiated BSA136T from its closest-related species. On the basis of our results, BSA136T and BSA150 can be considered to represent a novel species of the genus Mesorhizobium, for which the name Mesorhizobium sanjuanii sp. nov. is hereby proposed. The type strain of this species is BSA136T (=CECT 9305T=LMG 30060T), for which the draft genome sequence is available.}, } @article {pmid30063198, year = {2018}, author = {Choi, KD and Siddiqi, MZ and Liu, Q and Muhammad Shafi, S and Durrani, Y and Lee, SY and Kang, MS and Im, WT}, title = {Brevibacterium hankyongi sp. nov., isolated from compost.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2783-2788}, doi = {10.1099/ijsem.0.002886}, pmid = {30063198}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Brevibacterium/*classification/genetics/isolation & purification ; *Composting ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A Gram-positive, strictly aerobic, non-motile, milky-white to creamy coloured and rod-shaped bacterium, designated BS05T, was isolated from compost. Phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that the strain formed a distinct lineage within the genus Brevibacterium and was most closely related to Brevibacterium avium NCFB 3055T (96.3 %), Brevibacterium oceani BBH7T (96.2 %) and Brevibacterium epidermidis NBRC 14811T (96.1 %). The DNA G+C content was 62.3 mol%. The predominant quinone was MK-8(H2). The major fatty acids were anteiso-C15 : 0, anteiso-C17 : 0, iso-C16 : 0 and iso-C15 : 0. The cell-wall peptidoglycan of strain BS05T contained meso-diaminopimelic acid. The major polar lipid was phosphatidylglycerol. Moreover, the low sequence similarity of the 16S rRNA gene sequencing, physiological, biochemical and chemotaxonomic analyses allowed the phenotypic and genotypic differentiation of strain BS05T from the recognized species of the genus Brevibacterium. Therefore, strain BS05T represents a novel species of the genus Brevibacterium, for which the name Brevibacteriumhankyongi sp. nov. is proposed, with the type strain BS05T (=KACC 18875T=LMG 29562T).}, } @article {pmid30063102, year = {2018}, author = {Fox, RJ and Head, ML and Barber, I}, title = {Good parenting may not increase reproductive success under environmental extremes.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1638-1646}, doi = {10.1111/jeb.13358}, pmid = {30063102}, issn = {1420-9101}, support = {NE/F019440/1//UK Natural Environmental Research Council/ ; //UTS Chancellor's Postdoctoral Research Fellowship/ ; FT160100149//ARC Future Fellowship/ ; }, abstract = {For species exhibiting parental care, the way in which parents adjust care behaviour to compensate for environmental change potentially influences offspring survival and, ultimately, population viability. Using the three-spined stickleback (Gasterosteus aculeatus) - a species in which males provide parental care by building and tending a nest and fanning the eggs - we examined how low dissolved oxygen (DO) levels affect paternal care, embryo development and survival. Although levels of nest tending were unaffected by DO level, we found that larger males fanned their embryos more under low oxygen conditions. This resulted in faster rates of embryo development within the clutches of these larger males, but reduced embryo survival at 7 days post-fertilization compared to clutches of smaller males. Our results suggest that although parents may attempt to compensate for environmental change via alterations to care behaviour, their ability to do so can be dependent on parental phenotype. This sets up the potential for oxygen levels to act on the strength and direction of selection within populations. We discuss possible explanations for the surprising result that supposedly adaptive changes in care behaviour by large males (i.e. increased fanning) led to reduced embryo survival at 7 days post-fertilization, and whether, as a consequence, acute environmental conditions may have the potential to overwhelm selection on sexual traits.}, } @article {pmid30063098, year = {2018}, author = {Kojadinovic-Sirinelli, M and Villain, A and Puppo, C and Fon Sing, S and Prioretti, L and Hubert, P and Grégori, G and Zhang, Y and Sassi, JF and Claverie, JM and Blanc, G and Gontero, B}, title = {Exploring the microbiome of the "star" freshwater diatom Asterionella formosa in a laboratory context.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3601-3615}, doi = {10.1111/1462-2920.14337}, pmid = {30063098}, issn = {1462-2920}, support = {ANR-11-IDEX-0001-02//ANR/ ; ANR-10-INBS-0009//ANR/ ; //Aix-Marseille University/ ; 1166-39417//European FEDER Fund/ ; }, abstract = {Most of our knowledge on the mechanisms underlying diatom-bacterial interactions has been acquired through studies involving isolation of culturable partners. Here, we established a laboratory model of intermediate complexity between complex natural communities and laboratory pure culture models. We investigated the whole community formed by the freshwater diatom Asterionella formosa and its associated bacteria in a laboratory context, including both culturable and unculturable bacteria. Combining cellular and molecular approaches, we showed that in laboratory cultures, A. formosa microbiome was dynamic and comprised of numerous bacterial species (mainly Proteobacteria and Bacteroidetes). Using metagenomics, we explored several metabolic potentials present within the bacterial community. Our analyses suggested that bacteria were heterotrophic although a third of them (Alpha- and Beta-proteobacteria) could also be phototrophic. About 60% of the bacteria, phylogenetically diverse, could metabolize glycolate. The capacity to synthesize molecules such as B vitamins appeared unevenly distributed among bacteria. Altogether, our results brought insights into the bacterial diversity found in diatom-bacterial communities and hinted at metabolic interdependencies within the community that could result in diatom-bacterial and bacterial-bacterial interactions. The present work allowed us to explore the functional architecture of the bacterial community associated with A. formosa in culture and is complementary to field studies.}, } @article {pmid30062827, year = {2018}, author = {Matter, LB and Ares, MA and Abundes-Gallegos, J and Cedillo, ML and Yáñez, JA and Martínez-Laguna, Y and De la Cruz, MA and Girón, JA}, title = {The CpxRA stress response system regulates virulence features of avian pathogenic Escherichia coli.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3363-3377}, doi = {10.1111/1462-2920.14368}, pmid = {30062827}, issn = {1462-2920}, support = {MT78//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, abstract = {Avian pathogenic Escherichia coli (APEC) causes localized and systemic avian infections and is responsible for considerable economic losses in the poultry industry. This organism adheres and invades human and avian cells, however, the regulatory networks that dictate its virulence are largely unknown. The CpxRA two-component system is responsible for sensing and controlling outer-membrane stress and detecting misfolded proteins in the bacterial periplasmic space. CpxA is a membrane sensor kinase and CpxR is a cytoplasmic transcriptional regulator. In this study, we found that the CpxRA system regulates the virulence properties of APEC. Adherence, invasiveness, motility, production of type 1 fimbriae and biofilm were negatively affected in the ΔcpxA mutant indicating that the CpxA is required for full manifestation of these phenotypes. We also found that CpxR-P directly bound to the fimA promoter, locking the fimS region of type 1 fimbriae in the phase-OFF orientation. In addition, the absence of CpxA also reduced flagella production strongly suggesting that CpxRA regulates these two important surface organelles in APEC. This study provides compelling evidence of the role of the CpxRA two-component system in the regulation of virulence factors of avian pathogenic E. coli.}, } @article {pmid30062773, year = {2018}, author = {Wirth, S and Kunert, M and Ahrens, LM and Krause, K and Broska, S and Paetz, C and Kniemeyer, O and Jung, EM and Boland, W and Kothe, E}, title = {The regulator of G-protein signalling Thn1 links pheromone response to volatile production in Schizophyllum commune.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3684-3699}, doi = {10.1111/1462-2920.14369}, pmid = {30062773}, issn = {1462-2920}, support = {//Jena School for Microbial Communication (JSMC)/ ; //Friedrich Schiller University Jena/ ; }, abstract = {The regulator of G-protein signalling, Thn1, is involved in sexual development through pheromone signalling in the mushroom forming basidiomycete Schizophyllum commune affecting hyphal morphology and mating interactions. Thn1 plays a key role in coordinating sesquiterpene production, pheromone response and sexual development. The gene thn1 is transcriptionally regulated in response to mating with a role in clamp cell development and hydrophobin gene transcription. Further, it negatively regulates cAMP signalling and secondary metabolism. Disruption of thn1 affects dikaryotization by reducing clamp fusion and development with predominant non-fused pseudoclamps. Enhanced protein kinase A (PKA) activities in Δthn1 strains indicate that Thn1 regulates pheromone signalling by de-activating G-protein α subunits, which control cAMP-dependent PKA. The repressed formation of aerial hyphae could be linked to a reduced metabolic activity and to a transcriptional down-regulation of hyd6 and sc3 hydrophobin genes. Thn1 was also shown to be necessary for the biosynthesis of sesquiterpenes and an altered spectrum of sesquiterpenes in Δthn1 is linked to transcriptional up-regulation of biosynthesis genes. Proteome analysis indicated changes in cytoskeletal structure affecting actin localization, linking the major regulator Thn1 to growth and development of S. commune. The results support a role for Thn1 in G-protein signalling connecting development and secondary metabolism.}, } @article {pmid30062554, year = {2018}, author = {Kutralam-Muniasamy, G and Marsch, R and Pérez-Guevara, F}, title = {Investigation on the Evolutionary Relation of Diverse Polyhydroxyalkanoate Gene Clusters in Betaproteobacteria.}, journal = {Journal of molecular evolution}, volume = {86}, number = {7}, pages = {470-483}, pmid = {30062554}, issn = {1432-1432}, support = {CB-2014-01; 236285 and Fronteras de la Ciencia 2015-1: 016//CONACyT/ ; }, abstract = {Products of numerous genes (phaC, phaA, phaB, phaP, phaR, and phaZ) are involved in the synthesis and degradation processes of the ubiquitous prokaryotic polyhydroxyalkanoate (PHA) intracellular reserve storage system. In this study, we performed a bioinformatics analysis to identify PHA-related genes and proteins in the genome of 66 selected organisms (class: Betaproteobacteria) that occur in various habitats; besides, evolutionary trajectories of the PHA system are reported here. The identified PHA-related genes were organized into clusters, and the gene arrangement was highly diverse. The occurrence and distribution of PHA-related clusters revealed that a single cluster was primarily segmented into small gene groups among various genomes, which were further reorganized as novel clusters based on various functional genes. The individual phylogenies of gene and protein sequences supported that the clusters were assembled through the relocation of native orthologous genes that underwent insertion, deletion, and elongation events. Furthermore, the neighboring genes provided valuable evolutionary and functional cues regarding the conservation and maintenance of PHA-related genes in the genome. Overall, the aforementioned results strongly indicate the influence of horizontal gene transfer on the organization of PHA-related gene clusters. Therefore, our results reveal new insights into the organization, evolutionary history, and cluster conservation of the PHA-related gene inventories among Betaproteobacterial organisms.}, } @article {pmid30061758, year = {2018}, author = {Leitner, T and Romero-Severson, E}, title = {Phylogenetic patterns recover known HIV epidemiological relationships and reveal common transmission of multiple variants.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {983-988}, doi = {10.1038/s41564-018-0204-9}, pmid = {30061758}, issn = {2058-5276}, abstract = {The growth of human immunodeficiency virus (HIV) sequence databases resulting from drug resistance testing has motivated efforts using phylogenetic methods to assess how HIV spreads1-4. Such inference is potentially both powerful and useful for tracking the epidemiology of HIV and the allocation of resources to prevention campaigns. We recently used simulation and a small number of illustrative cases to show that certain phylogenetic patterns are associated with different types of epidemiological linkage5. Our original approach was later generalized for large next-generation sequencing datasets and implemented as a free computational pipeline6. Previous work has claimed that direction and directness of transmission could not be established from phylogeny because one could not be sure that there were no intervening or missing links involved7-9. Here, we address this issue by investigating phylogenetic patterns from 272 previously identified HIV transmission chains with 955 transmission pairs representing diverse geography, risk groups, subtypes, and genomic regions. These HIV transmissions had known linkage based on epidemiological information such as partner studies, mother-to-child transmission, pairs identified by contact tracing, and criminal cases. We show that the resulting phylogeny inferred from real HIV genetic sequences indeed reveals distinct patterns associated with direct transmission contra transmissions from a common source. Thus, our results establish how to interpret phylogenetic trees based on HIV sequences when tracking who-infected-whom, when and how genetic information can be used for improved tracking of HIV spread. We also investigate limitations that stem from limited sampling and genetic time-trends in the donor and recipient HIV populations.}, } @article {pmid30061757, year = {2018}, author = {Liu, W and Zhou, Y and Peng, T and Zhou, P and Ding, X and Li, Z and Zhong, H and Xu, Y and Chen, S and Hang, HC and Shao, F}, title = {Nε-fatty acylation of multiple membrane-associated proteins by Shigella IcsB effector to modulate host function.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {996-1009}, doi = {10.1038/s41564-018-0215-6}, pmid = {30061757}, issn = {2058-5276}, abstract = {Shigella flexneri, an intracellular Gram-negative bacterium causative for shigellosis, employs a type III secretion system to deliver virulence effectors into host cells. One such effector, IcsB, is critical for S. flexneri intracellular survival and pathogenesis, but its mechanism of action is unknown. Here, we discover that IcsB is an 18-carbon fatty acyltransferase catalysing lysine Nε-fatty acylation. IcsB disrupted the actin cytoskeleton in eukaryotes, resulting from Nε-fatty acylation of RhoGTPases on lysine residues in their polybasic region. Chemical proteomic profiling identified about 60 additional targets modified by IcsB during infection, which were validated by biochemical assays. Most IcsB targets are membrane-associated proteins bearing a lysine-rich polybasic region, including members of the Ras, Rho and Rab families of small GTPases. IcsB also modifies SNARE proteins and other non-GTPase substrates, suggesting an extensive interplay between S. flexneri and host membrane trafficking. IcsB is localized on the Shigella-containing vacuole to fatty-acylate its targets. Knockout of CHMP5-one of the IcsB targets and a component of the ESCRT-III complex-specifically affected S. flexneri escape from host autophagy. The unique Nε-fatty acyltransferase activity of IcsB and its altering of the fatty acylation landscape of host membrane proteomes represent an unprecedented mechanism in bacterial pathogenesis.}, } @article {pmid30061756, year = {2018}, author = {Kent, AG and Garcia, CA and Martiny, AC}, title = {Increased biofilm formation due to high-temperature adaptation in marine Roseobacter.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {989-995}, pmid = {30061756}, issn = {2058-5276}, support = {NNX15AN56H//NASA/United States ; T32 EB009418/EB/NIBIB NIH HHS/United States ; }, abstract = {Ocean temperatures will increase significantly over the next 100 years due to global climate change1. As temperatures increase beyond current ranges, it is unclear how adaptation will impact the distribution and ecological role of marine microorganisms2. To address this major unknown, we imposed a stressful high-temperature regime for 500 generations on a strain from the abundant marine Roseobacter clade. High-temperature-adapted isolates significantly improved their fitness but also increased biofilm formation at the air-liquid interface. Furthermore, this altered lifestyle was coupled with genomic changes linked to biofilm formation in individual isolates, and was also dominant in evolved populations. We hypothesize that the increasing biofilm formation was driven by lower oxygen availability at elevated temperature, and we observe a relative fitness increase at lower oxygen. The response is uniquely different from that of Escherichia coli adapted to high temperature3 (only 3% of mutated genes were shared in both studies). Thus, future increased temperatures could have a direct effect on organismal physiology and an indirect effect via a decrease in ocean oxygen solubility, leading to an alteration in microbial lifestyle.}, } @article {pmid30061737, year = {2018}, author = {Nielsen, JB and Thorolfsdottir, RB and Fritsche, LG and Zhou, W and Skov, MW and Graham, SE and Herron, TJ and McCarthy, S and Schmidt, EM and Sveinbjornsson, G and Surakka, I and Mathis, MR and Yamazaki, M and Crawford, RD and Gabrielsen, ME and Skogholt, AH and Holmen, OL and Lin, M and Wolford, BN and Dey, R and Dalen, H and Sulem, P and Chung, JH and Backman, JD and Arnar, DO and Thorsteinsdottir, U and Baras, A and O'Dushlaine, C and Holst, AG and Wen, X and Hornsby, W and Dewey, FE and Boehnke, M and Kheterpal, S and Mukherjee, B and Lee, S and Kang, HM and Holm, H and Kitzman, J and Shavit, JA and Jalife, J and Brummett, CM and Teslovich, TM and Carey, DJ and Gudbjartsson, DF and Stefansson, K and Abecasis, GR and Hveem, K and Willer, CJ}, title = {Biobank-driven genomic discovery yields new insight into atrial fibrillation biology.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1234-1239}, doi = {10.1038/s41588-018-0171-3}, pmid = {30061737}, issn = {1546-1718}, support = {R01 HL124232/HL/NHLBI NIH HHS/United States ; R35 HL135824/HL/NHLBI NIH HHS/United States ; }, abstract = {To identify genetic variation underlying atrial fibrillation, the most common cardiac arrhythmia, we performed a genome-wide association study of >1,000,000 people, including 60,620 atrial fibrillation cases and 970,216 controls. We identified 142 independent risk variants at 111 loci and prioritized 151 functional candidate genes likely to be involved in atrial fibrillation. Many of the identified risk variants fall near genes where more deleterious mutations have been reported to cause serious heart defects in humans (GATA4, MYH6, NKX2-5, PITX2, TBX5)1, or near genes important for striated muscle function and integrity (for example, CFL2, MYH7, PKP2, RBM20, SGCG, SSPN). Pathway and functional enrichment analyses also suggested that many of the putative atrial fibrillation genes act via cardiac structural remodeling, potentially in the form of an 'atrial cardiomyopathy'2, either during fetal heart development or as a response to stress in the adult heart.}, } @article {pmid30061736, year = {2018}, author = {Springer, NM and Anderson, SN and Andorf, CM and Ahern, KR and Bai, F and Barad, O and Barbazuk, WB and Bass, HW and Baruch, K and Ben-Zvi, G and Buckler, ES and Bukowski, R and Campbell, MS and Cannon, EKS and Chomet, P and Dawe, RK and Davenport, R and Dooner, HK and Du, LH and Du, C and Easterling, KA and Gault, C and Guan, JC and Hunter, CT and Jander, G and Jiao, Y and Koch, KE and Kol, G and Köllner, TG and Kudo, T and Li, Q and Lu, F and Mayfield-Jones, D and Mei, W and McCarty, DR and Noshay, JM and Portwood, JL and Ronen, G and Settles, AM and Shem-Tov, D and Shi, J and Soifer, I and Stein, JC and Stitzer, MC and Suzuki, M and Vera, DL and Vollbrecht, E and Vrebalov, JT and Ware, D and Wei, S and Wimalanathan, K and Woodhouse, MR and Xiong, W and Brutnell, TP}, title = {The maize W22 genome provides a foundation for functional genomics and transposon biology.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1282-1288}, doi = {10.1038/s41588-018-0158-0}, pmid = {30061736}, issn = {1546-1718}, abstract = {The maize W22 inbred has served as a platform for maize genetics since the mid twentieth century. To streamline maize genome analyses, we have sequenced and de novo assembled a W22 reference genome using short-read sequencing technologies. We show that significant structural heterogeneity exists in comparison to the B73 reference genome at multiple scales, from transposon composition and copy number variation to single-nucleotide polymorphisms. The generation of this reference genome enables accurate placement of thousands of Mutator (Mu) and Dissociation (Ds) transposable element insertions for reverse and forward genetics studies. Annotation of the genome has been achieved using RNA-seq analysis, differential nuclease sensitivity profiling and bisulfite sequencing to map open reading frames, open chromatin sites and DNA methylation profiles, respectively. Collectively, the resources developed here integrate W22 as a community reference genome for functional genomics and provide a foundation for the maize pan-genome.}, } @article {pmid30061735, year = {2018}, author = {Sun, S and Zhou, Y and Chen, J and Shi, J and Zhao, H and Zhao, H and Song, W and Zhang, M and Cui, Y and Dong, X and Liu, H and Ma, X and Jiao, Y and Wang, B and Wei, X and Stein, JC and Glaubitz, JC and Lu, F and Yu, G and Liang, C and Fengler, K and Li, B and Rafalski, A and Schnable, PS and Ware, DH and Buckler, ES and Lai, J}, title = {Extensive intraspecific gene order and gene structural variations between Mo17 and other maize genomes.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1289-1295}, doi = {10.1038/s41588-018-0182-0}, pmid = {30061735}, issn = {1546-1718}, abstract = {Maize is an important crop with a high level of genome diversity and heterosis. The genome sequence of a typical female line, B73, was previously released. Here, we report a de novo genome assembly of a corresponding male representative line, Mo17. More than 96.4% of the 2,183 Mb assembled genome can be accounted for by 362 scaffolds in ten pseudochromosomes with 38,620 annotated protein-coding genes. Comparative analysis revealed large gene-order and gene structural variations: approximately 10% of the annotated genes were mutually nonsyntenic, and more than 20% of the predicted genes had either large-effect mutations or large structural variations, which might cause considerable protein divergence between the two inbred lines. Our study provides a high-quality reference-genome sequence of an important maize germplasm, and the intraspecific gene order and gene structural variations identified should have implications for heterosis and genome evolution.}, } @article {pmid30061649, year = {2018}, author = {}, title = {Pinning extreme weather on climate change is now routine and reliable science.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {5}, doi = {10.1038/d41586-018-05839-x}, pmid = {30061649}, issn = {1476-4687}, mesh = {*Climate Change ; Disasters ; *Weather ; }, } @article {pmid30061648, year = {2018}, author = {Schiermeier, Q}, title = {Droughts, heatwaves and floods: How to tell when climate change is to blame.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {20-22}, doi = {10.1038/d41586-018-05849-9}, pmid = {30061648}, issn = {1476-4687}, mesh = {Atmosphere/chemistry ; Climate Change/*statistics & numerical data ; Droughts/*statistics & numerical data ; Europe ; Floods/*statistics & numerical data ; *Forecasting ; Geographic Mapping ; *Hot Temperature ; Human Activities ; Models, Theoretical ; *Natural Disasters ; Probability ; Russia ; South Africa ; *Weather ; Wildfires/statistics & numerical data ; }, } @article {pmid30061647, year = {2018}, author = {Archibald, J}, title = {The band of biologists who redrew the tree of life.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {26-27}, doi = {10.1038/d41586-018-05827-1}, pmid = {30061647}, issn = {1476-4687}, } @article {pmid30061646, year = {2018}, author = {Crease, RP}, title = {Ideal witness: a physicist takes on the world.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {28}, doi = {10.1038/d41586-018-05829-z}, pmid = {30061646}, issn = {1476-4687}, } @article {pmid30061645, year = {2018}, author = {Kiser, B}, title = {Ebola from the front lines, US aviation's female high-fliers, and a history of science journals: Books in brief.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {27}, doi = {10.1038/d41586-018-05828-0}, pmid = {30061645}, issn = {1476-4687}, } @article {pmid30061644, year = {2018}, author = {Mayer, C and Fishell, G}, title = {Developing neurons are innately inclined to learn on the job.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {39-40}, doi = {10.1038/d41586-018-05737-2}, pmid = {30061644}, issn = {1476-4687}, } @article {pmid30061643, year = {2018}, author = {Wei, J and Yewdell, JW}, title = {Peptide secretion triggers diabetes.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {33-34}, doi = {10.1038/d41586-018-05710-z}, pmid = {30061643}, issn = {1476-4687}, mesh = {Blood Glucose ; Diabetes Mellitus, Type 1 ; Exocytosis ; Humans ; *Insulin ; *Islets of Langerhans ; Lymphoid Tissue ; }, } @article {pmid30061642, year = {2018}, author = {Winkler, F}, title = {Leukaemia follows a blood-vessel track to enter the nervous system.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {35-36}, doi = {10.1038/d41586-018-05693-x}, pmid = {30061642}, issn = {1476-4687}, mesh = {*Central Nervous System ; Humans ; *Leukemia ; }, } @article {pmid30061641, year = {2018}, author = {Hui, S and Rabinowitz, JD}, title = {An unexpected trigger for calorie burning in brown fat.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {38-39}, doi = {10.1038/d41586-018-05619-7}, pmid = {30061641}, issn = {1476-4687}, mesh = {Adipose Tissue ; *Adipose Tissue, Brown ; Energy Intake ; Energy Metabolism ; *Succinic Acid ; Thermogenesis ; }, } @article {pmid30061620, year = {2018}, author = {Chen, TG and Barton, LM and Lin, Y and Tsien, J and Kossler, D and Bastida, I and Asai, S and Bi, C and Chen, JS and Shan, M and Fang, H and Fang, FG and Choi, HW and Hawkins, L and Qin, T and Baran, PS}, title = {Building C(sp3)-rich complexity by combining cycloaddition and C-C cross-coupling reactions.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {350-354}, pmid = {30061620}, issn = {1476-4687}, support = {R35 GM118176/GM/NIGMS NIH HHS/United States ; }, abstract = {Prized for their ability to rapidly generate chemical complexity by building new ring systems and stereocentres1, cycloaddition reactions have featured in numerous total syntheses2 and are a key component in the education of chemistry students3. Similarly, carbon-carbon (C-C) cross-coupling methods are integral to synthesis because of their programmability, modularity and reliability4. Within the area of drug discovery, an overreliance on cross-coupling has led to a disproportionate representation of flat architectures that are rich in carbon atoms with orbitals hybridized in an sp2 manner5. Despite the ability of cycloadditions to introduce multiple carbon sp3 centres in a single step, they are less used6. This is probably because of their lack of modularity, stemming from the idiosyncratic steric and electronic rules for each specific type of cycloaddition. Here we demonstrate a strategy for combining the optimal features of these two chemical transformations into one simple sequence, to enable the modular, enantioselective, scalable and programmable preparation of useful building blocks, natural products and lead scaffolds for drug discovery.}, } @article {pmid30061565, year = {2018}, author = {Ghazoul, J and Kleinschroth, F}, title = {A global perspective is needed to protect environmental defenders.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1340-1342}, doi = {10.1038/s41559-018-0640-1}, pmid = {30061565}, issn = {2397-334X}, } @article {pmid30061564, year = {2018}, author = {Louca, S and Shih, PM and Pennell, MW and Fischer, WW and Parfrey, LW and Doebeli, M}, title = {Bacterial diversification through geological time.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1458-1467}, doi = {10.1038/s41559-018-0625-0}, pmid = {30061564}, issn = {2397-334X}, abstract = {Numerous studies have estimated plant and animal diversification dynamics; however, no comparable rigorous estimates exist for bacteria-the most ancient and widespread form of life on Earth. Here, we analyse phylogenies comprising up to 448,112 bacterial lineages to reconstruct global bacterial diversification dynamics. To handle such large phylogenies, we developed methods based on the statistical properties of infinitely large trees. We further analysed sequencing data from 60 environmental studies to determine the fraction of extant bacterial diversity missing from the phylogenies-a crucial parameter for estimating speciation and extinction rates. We estimate that there are about 1.4-1.9 million extant bacterial lineages when lineages are defined by 99% similarity in the 16S ribosomal RNA gene, and that bacterial diversity has been continuously increasing over the past 1 billion years (Gyr). Recent bacterial extinction rates are estimated at 0.03-0.05 per lineage per million years (lineage-1 Myr-1), and are only slightly below estimated recent bacterial speciation rates. Most bacterial lineages ever to have inhabited this planet are estimated to be extinct. Our findings disprove the notion that bacteria are unlikely to go extinct, and provide a valuable perspective on the evolutionary history of a domain of life with a sparse and cryptic fossil record.}, } @article {pmid30061563, year = {2018}, author = {Eppinga, MB and Baudena, M and Johnson, DJ and Jiang, J and Mack, KML and Strand, AE and Bever, JD}, title = {Frequency-dependent feedback constrains plant community coexistence.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1403-1407}, doi = {10.1038/s41559-018-0622-3}, pmid = {30061563}, issn = {2397-334X}, abstract = {Ecological theory suggests that coexistence of many species within communities requires negative frequency-dependent feedbacks to prevent exclusion of the least fit species. For plant communities, empirical evidence of negative frequency dependence driving species coexistence and diversity patterns is rapidly accumulating, but connecting these findings to theory has been difficult as corresponding theoretical frameworks only consider small numbers of species. Here, we show how frequency-dependent feedback constrains community coexistence, regardless of the number of species and inherent fitness inequalities between them. Any interaction network can be characterized by a single community interaction coefficient, IC, which determines whether community-level feedback is positive or negative. Negative feedback is a necessary (but not sufficient) condition for persistence of the entire community. Even in cases where the coexistence equilibrium state cannot recover from perturbations, IC < 0 can enable species persistence via cyclic succession. The number of coexisting species is predicted to increase with the average strength of negative feedback. This prediction is supported by patterns of tree species diversity in more than 200,000 deciduous forest plots in the eastern United States, which can be reproduced in simulations that span the observed range of community feedback. By providing a quantitative metric for the strength of negative feedback needed for coexistence, we can now integrate theory and empirical data to test whether observed feedback-diversity correlations are strong enough to infer causality.}, } @article {pmid30061562, year = {2018}, author = {Schöb, C and Brooker, RW and Zuppinger-Dingley, D}, title = {Evolution of facilitation requires diverse communities.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1381-1385}, doi = {10.1038/s41559-018-0623-2}, pmid = {30061562}, issn = {2397-334X}, abstract = {Diverse experimental plant communities are more productive than monocultures. The increase of this biodiversity effect over time has been attributed to evolutionary selection for complementarity in mixtures. Here we show that evolutionary selection for enhanced net facilitative plant interactions occurred only in mixtures, while evolutionary selection for reduced net competition occurred in mixtures with mixture coexistence history and monocultures with monoculture coexistence history. Widespread declines in natural and agricultural biodiversity could therefore compromise potential evolution of facilitative interactions, that is, cornerstone processes in nature conservation and the development of sustainable agriculture.}, } @article {pmid30061561, year = {2018}, author = {Stewart, AD and Rice, WR}, title = {Arrest of sex-specific adaptation during the evolution of sexual dimorphism in Drosophila.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1507-1513}, doi = {10.1038/s41559-018-0613-4}, pmid = {30061561}, issn = {2397-334X}, abstract = {Sexually antagonistic selection arises when a trait expressed in both sexes (a shared trait) is selected towards different, sex-specific optima. Sex-discordant selection causes different alleles to be favoured in each sex (intralocus sexual conflict). A key parameter responsible for generating this conflict is the intersexual genetic correlation (rMF), which determines the degree to which heritable genetic variation for the shared trait produces a similar phenotype in both sexes. A strong, positive rMF interferes with adaptation when there is sex-discordant selection. In principle, the rMF can evolve in response to sex-discordant selection: the faster it declines, the faster the resolution of intralocus sexual conflict. Here, we use Drosophila melanogaster to quantify the time scale over which a strong, positive rMF impedes a response to sex-discordant selection for a canonical quantitative trait (body size) with an exceptionally long (250 generations) selection experiment for a complex multicellular organism. We found that, compared with rapid and substantial evolution under sex-concordant selection, a high rMF arrested sex-specific adaptation for 100 generations in females and a minimum of 250 generations in males. Our study demonstrates that a high rMF can lead to a protracted period of adaptive stalemate during the evolution of sexual dimorphism.}, } @article {pmid30061560, year = {2018}, author = {Harold, S}, title = {Cross-border science in the Middle East.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1346-1347}, doi = {10.1038/s41559-018-0635-y}, pmid = {30061560}, issn = {2397-334X}, } @article {pmid30061471, year = {2018}, author = {Mellini, P and Marrocco, B and Borovika, D and Polletta, L and Carnevale, I and Saladini, S and Stazi, G and Zwergel, C and Trapencieris, P and Ferretti, E and Tafani, M and Valente, S and Mai, A}, title = {Correction to 'Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, doi = {10.1098/rstb.2018.0305}, pmid = {30061471}, issn = {1471-2970}, } @article {pmid30061470, year = {2018}, author = {Naccache, L}, title = {Why and how access consciousness can account for phenomenal consciousness.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061470}, issn = {1471-2970}, abstract = {According to a popular distinction proposed by the philosopher Ned Block in 1995, our conscious experience would overflow the very limited set of what we can consciously report to ourselves and to others. He proposed to coin this limited consciousness 'Access Consciousness' (A-Cs) and to define 'Phenomenal Consciousness' as a much richer subjective experience that is not accessed but that would still delineate the extent of consciousness. In this article, I review and develop five major problems raised by this theory, and show how a strict A-Cs theory can account for our conscious experience. I illustrate such an A-Cs account within the global workspace (GW) theoretical framework, and revisit some seminal empirical findings and neuropsychological syndromes. In this strict A-Cs perspective, subjective reports are not conceived as the mere passive broadcasting of information to the GW, but as resulting from a dynamic and active chain of internal processes that notably include interpretative and belief attribution stages. Finally, I list a set of testable predictions, of unsolved questions and of some counterintuitive hypotheses.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061469, year = {2018}, author = {Fazekas, P and Nemeth, G}, title = {Dream experiences and the neural correlates of perceptual consciousness and cognitive access.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061469}, issn = {1471-2970}, abstract = {This paper approaches the debate whether perceptual consciousness requires cognitive access from the perspective of dream studies, and investigates what kind of findings could support the opposing views of this debate. Two kinds of arguments are discussed, one that claims that the hypoactivity of the dorsolateral prefrontal cortex in rapid eye movement sleep is directly relevant, and another that proposes that locating the neural correlates of dream experiences can indirectly inform the debate. It is argued that under closer reflection, neither the classical claim about dorsolateral prefrontal cortex hypoactivity nor the more recent emphasis on general posterior hot zone activity during dreaming stand up to scrutiny. White dreaming is identified as the phenomenon that, nevertheless, holds the most promise to have an impact on the debate. Going beyond the topic if studying dreams can contribute to this debate, it is argued that cognitive access is not a monolithic phenomenon, and its neural correlates are not well understood. There seems to be a relevant form of cognitive access that can operate in the absence of activity in the dorsolateral prefrontal cortex, and maybe also in the whole frontal region. If so, then exclusive posterior activation during conscious experiences might very well be compatible with the hypothesis that perceptual consciousness requires cognitive access.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061468, year = {2018}, author = {Ward, EJ}, title = {Downgraded phenomenology: how conscious overflow lost its richness.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061468}, issn = {1471-2970}, abstract = {Our in-the-moment experience of the world can feel vivid and rich, even when we cannot describe our experience due to limitations of attention, memory or other cognitive processes. But the nature of visual awareness is quite sparse, as suggested by the phenomena of failures of awareness, such as change blindness and inattentional blindness. I will argue that once failures of memory or failures of comparison are ruled out as explanations for these phenomena, they present strong evidence against rich awareness. To accommodate and explain these massive failures of awareness, any theory of phenomenal consciousness must downgrade phenomenology to a degree where it is functionless or, ironically, does not reflect what we experience.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061467, year = {2018}, author = {Usher, M and Bronfman, ZZ and Talmor, S and Jacobson, H and Eitam, B}, title = {Consciousness without report: insights from summary statistics and inattention 'blindness'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061467}, issn = {1471-2970}, abstract = {We contrast two theoretical positions on the relation between phenomenal and access consciousness. First, we discuss previous data supporting a mild Overflow position, according to which transient visual awareness can overflow report. These data are open to two interpretations: (i) observers transiently experience specific visual elements outside attentional focus without encoding them into working memory; (ii) no specific visual elements but only statistical summaries are experienced in such conditions. We present new data showing that under data-limited conditions observers cannot discriminate a simple relation (same versus different) without discriminating the elements themselves and, based on additional computational considerations, we argue that this supports the first interpretation: summary statistics (same/different) are grounded on the transient experience of elements. Second, we examine recent data from a variant of 'inattention blindness' and argue that contrary to widespread assumptions, it provides further support for Overflow by highlighting another factor, 'task relevance', which affects the ability to conceptualize and report (but not experience) visual elements.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061466, year = {2018}, author = {Overgaard, M}, title = {Phenomenal consciousness and cognitive access.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061466}, issn = {1471-2970}, abstract = {In consciousness research, it is common to distinguish between phenomenal consciousness and access consciousness. Recently, a number of scientists have attempted to show that phenomenal content can be empirically separated from cognitive access and, accordingly, that the mental content that is accessed is not (always) identical to the content that is experienced. One notable position is that of Ned Block who suggests that phenomenal content overflows cognitive access. I will review the evidence and show that existing data, in fact, do not demonstrate overflow. I will further argue that overflow is theoretically possible-yet highly difficult to empirically demonstrate-under the condition that 'cognitive access' is defined as working memory or attention. However, if 'access' is defined as information becoming 'cognitively available', in a broader sense, I will argue that a separation between subjective experience and access is impossible.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061465, year = {2018}, author = {Matthews, J and Schröder, P and Kaunitz, L and van Boxtel, JJA and Tsuchiya, N}, title = {Conscious access in the near absence of attention: critical extensions on the dual-task paradigm.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061465}, issn = {1471-2970}, abstract = {Whether conscious perception requires attention remains a topic of intense debate. While certain complex stimuli such as faces and animals can be discriminated outside the focus of spatial attention, many simpler stimuli cannot. Because such evidence was obtained in dual-task paradigms involving no measure of subjective insight, it remains unclear whether accurate discrimination of unattended complex stimuli is the product of automatic, unconscious processing, as in blindsight, or is accessible to consciousness. Furthermore, these paradigms typically require extensive training over many hours, bringing into question whether this phenomenon can be achieved in naive subjects. We developed a novel dual-task paradigm incorporating confidence ratings to calculate metacognition and adaptive staircase procedures to reduce training. With minimal training, subjects were able to discriminate face-gender in the near absence of top-down attentional amplification, while also displaying above-chance metacognitive accuracy. By contrast, the discrimination of simple coloured discs was significantly impaired and metacognitive accuracy dropped to chance-level, even in a partial-report condition. In a final experiment, we used blended face/disc stimuli and confirmed that face-gender but not colour orientation can be discriminated in the dual task. Our results show direct evidence for metacognitive conscious access in the near absence of attention for complex, but not simple, stimuli.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061464, year = {2018}, author = {Stazicker, J}, title = {Partial report is the wrong paradigm.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061464}, issn = {1471-2970}, abstract = {Is consciousness independent of the general-purpose information processes known as 'cognitive access'? The dominant methodology for supporting this independence hypothesis appeals to partial report experiments as evidence for perceptual consciousness in the absence of cognitive access. Using a standard model of evidential support, and reviewing recent elaborations of the partial report paradigm, this article argues that the paradigm has the wrong structure to support the independence hypothesis. Like reports in general, a subject's partial report is evidence that she is conscious of information only where that information is cognitively accessed. So, partial report experiments could dissociate consciousness from cognitive access only if there were uncontroversial evidence for consciousness that did not imply reportability. There is no such evidence. An alternative, broadly Marrian methodology for supporting the independence hypothesis is suggested, and some challenges to it outlined. This methodology does not require experimental evidence for consciousness in the absence of cognitive access. Instead, it focuses on a function of perceptual consciousness when a stimulus is cognitively accessed. If the processes best suited to implement this function exclude cognitive access, the independence hypothesis will be supported. One relevant function of consciousness may be reflected in reason-based psychological explanations of a subject's behaviour.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061463, year = {2018}, author = {Sergent, C}, title = {The offline stream of conscious representations.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061463}, issn = {1471-2970}, abstract = {When do we become conscious of a stimulus after its presentation? We would all agree that this necessarily takes time and that it is not instantaneous. Here, I would like to propose not only that conscious access is delayed relative to the external stimulation, but also that it can flexibly desynchronize from external stimulation; it can process some information 'offline', if and when it becomes relevant. Thus, in contrast with initial sensory processing, conscious experience might not strictly follow the sequence of events in the environment. In this article, I will review gathering evidence in favour of this proposition. I will argue that it offers a coherent framework for explaining a great variety of observations in the domain of perception, sensory memory and working memory: the psychological refractory period, the attentional blink, post-dictive phenomena, iconic memory, latent working memory and the newly described retro-perception phenomenon. I will integrate this proposition to the global neuronal workspace model and consider possible underlying brain mechanisms. Finally, I will argue that this capacity to process information 'offline' might have made conscious processing evolutionarily advantageous in spite of its sluggishness and capacity limitations.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061462, year = {2018}, author = {Pitts, MA and Lutsyshyna, LA and Hillyard, SA}, title = {The relationship between attention and consciousness: an expanded taxonomy and implications for 'no-report' paradigms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061462}, issn = {1471-2970}, abstract = {Tensions between global neuronal workspace theory and recurrent processing theory have sparked much debate in the field of consciousness research. Here, we focus on one of the key distinctions between these theories: the proposed relationship between attention and consciousness. By reviewing recent empirical evidence, we argue that both theories contain key insights and that certain aspects of each theory can be reconciled into a novel framework that may help guide future research. Alternative theories are also considered, including attended intermediate-level representations theory, integrated information theory and higher order thought theory. With the aim of offering a fresh and nuanced perspective to current theoretical debates, an updated taxonomy of conscious and non-conscious states is proposed. This framework maps a wider spectrum of conscious states by incorporating contemporary views from cognitive neuroscience regarding the variety of attentional mechanisms that are known to interact with sensory processing. Whether certain types of attention are necessary for phenomenal and access consciousness is considered and incorporated into this extended taxonomy. To navigate this expanded space, we review recent 'no-report' paradigms and address several methodological misunderstandings in order to pave a clear path forward for identifying the neural basis of perceptual awareness.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061461, year = {2018}, author = {Phillips, I}, title = {The methodological puzzle of phenomenal consciousness.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061461}, issn = {1471-2970}, abstract = {Is phenomenal consciousness constitutively related to cognitive access? Despite being a fundamental issue for any science of consciousness, its empirical study faces a severe methodological puzzle. Recent years have seen numerous attempts to address this puzzle, either in practice, by offering evidence for a positive or negative answer, or in principle, by proposing a framework for eventual resolution. The present paper critically considers these endeavours, including partial-report, metacognitive and no-report paradigms, as well as the theoretical proposal that we can make progress by studying phenomenal consciousness as a natural kind. It is argued that the methodological puzzle remains obdurately with us and that, for now, we must adopt an attitude of humility towards the phenomenal.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061460, year = {2018}, author = {Mogensen, J and Overgaard, M}, title = {Reorganization of the connectivity between elementary functions as a common mechanism of phenomenal consciousness and working memory: from functions to strategies.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061460}, issn = {1471-2970}, abstract = {In the present communication, phenomenal consciousness, access consciousness and the closely related concept of working memory are presented in the context of a neurocognitive model-the REF (reorganization of elementary functions) framework. The REF framework is based on connectionist networks within which the 'units' are advanced processing modules called elementary functions (EFs). In this framework, the focus is on dynamically changeable 'strategies'-based on reorganizations of the connectivity between EFs-rather than on the more traditional 'cognitive functions'. The background for the REF framework and especially how the neural correlate of consciousness is understood within these models is summarized. According to the REF framework, phenomenal consciousness cannot 'overflow' availability of information for action. Phenomenal consciousness may, however, overflow working memory because working memory in the present context is seen as a surface phenomenon reflecting underlying dynamic strategies-influenced by both experience and situational factors.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061459, year = {2018}, author = {Odegaard, B and Chang, MY and Lau, H and Cheung, SH}, title = {Inflation versus filling-in: why we feel we see more than we actually do in peripheral vision.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061459}, issn = {1471-2970}, abstract = {Do we perceive fine details in the visual periphery? Here, we propose that phenomenology in the visual periphery can be characterized by an inflated sense of perceptual capacity, as observers overestimate the quality of their perceptual inputs. Distinct from the well-known perceptual phenomenon of 'filling-in' where perceptual content is generated or completed endogenously, inflation can be characterized by incorrect introspection at the subjective level. The perceptual content itself may be absent or weak (i.e. not necessarily filled-in), and yet such content is mistakenly regarded by the system as rich. Behaviourally, this can be reflected by metacognitive deficits in the degree to which confidence judgements track task accuracy, and decisional biases for observers to think particular items are present, even when they are not. In two experiments using paradigms that exploit unique attributes of peripheral vision (crowding and summary statistics), we provide evidence that both types of deficits are present in peripheral vision, as observers' reports are marked by overconfidence in discrimination judgements and high numbers of false alarms in detection judgements. We discuss potential mechanisms that may be the cause of inflation and propose future experiments to further explore this unique sensory phenomenon.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061458, year = {2018}, author = {Lamme, VAF}, title = {Challenges for theories of consciousness: seeing or knowing, the missing ingredient and how to deal with panpsychism.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061458}, issn = {1471-2970}, abstract = {Significant progress has been made in the study of consciousness. Promising theories have been developed and a wealth of experimental data has been generated, both guiding us towards a better understanding of this complex phenomenon. However, new challenges have surfaced. Is visual consciousness about the seeing or the knowing that you see? Controversy about whether the conscious experience is better explained by theories that focus on phenomenal (P-consciousness) or cognitive aspects (A-consciousness) remains, and the debate seems to reach a stalemate. Can we ever resolve this? A further challenge is that many theories of consciousness seem to endorse high degrees of panpsychism-the notion that all beings or even lifeless objects have conscious experience. Should we accept this, or does it imply that these theories require further ingredients that would put a lower bound on beings or devices that have conscious experience? If so, what could these 'missing ingredients' be? These challenges are discussed, and potential solutions are offered.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061457, year = {2018}, author = {Gross, S}, title = {Perceptual consciousness and cognitive access from the perspective of capacity-unlimited working memory.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061457}, issn = {1471-2970}, abstract = {Theories of consciousness divide over whether perceptual consciousness is rich or sparse in specific representational content and whether it requires cognitive access. These two issues are often treated in tandem because of a shared assumption that the representational capacity of cognitive access is fairly limited. Recent research on working memory challenges this shared assumption. This paper argues that abandoning the assumption undermines post-cue-based 'overflow' arguments, according to which perceptual consciousness is rich and does not require cognitive access. Abandoning it also dissociates the rich/sparse debate from the access question. The paper then explores attempts to reformulate overflow theses in ways that do not require the assumption of limited capacity. Finally, it discusses the problem of relating seemingly non-probabilistic perceptual consciousness to the probabilistic representations posited by the models that challenge conceptions of cognitive access as capacity-limited.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061456, year = {2018}, author = {Dennett, DC}, title = {Facing up to the hard question of consciousness.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061456}, issn = {1471-2970}, abstract = {The so-called hard problem of consciousness is a chimera, a distraction from the hard question of consciousness, which is once some content reaches consciousness, 'then what happens?'. This question is seldom properly asked, for reasons good and bad, but when asked it opens up avenues of research that promise to dissolve the hard problem and secure a scientifically sound theory of how the human brain produces the (sometimes illusory) convictions that mislead us.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061455, year = {2018}, author = {Block, N}, title = {If perception is probabilistic, why does it not seem probabilistic?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061455}, issn = {1471-2970}, abstract = {The success of the Bayesian perspective in explaining perceptual phenomena has motivated the view that perceptual representation is probabilistic. But if perceptual representation is probabilistic, why does normal conscious perception not reflect the full probability functions that the probabilistic point of view endorses? For example, neurons in cortical area MT that respond to the direction of motion are broadly tuned: a patch of cortex that is tuned to vertical motion also responds to horizontal motion, but when we see vertical motion, foveally, in good conditions, it does not look at all horizontal. The standard solution in terms of sampling runs into the problem that sampling is an account of perceptual decision rather than perception. This paper argues that the best Bayesian approach to this problem does not require probabilistic representation.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061454, year = {2018}, author = {Fazekas, P and Overgaard, M}, title = {Perceptual consciousness and cognitive access: an introduction.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1755}, pages = {}, pmid = {30061454}, issn = {1471-2970}, abstract = {The problem of perceptual consciousness-the question of how our subjective experiences (colours as we see them; sounds as we hear them; tastes, etc., as we feel them) could be accounted for in terms of brain processes-is often regarded as the greatest unsolved mystery of our times. In recent literature, one of the most pressing questions in this regard is whether the neural basis of perceptual consciousness is independent of the neural basis of cognitive access mechanisms that make reporting and reflecting on conscious experiences possible. The Theme Issue focuses on this central problem of consciousness research and aims to contribute to the field by critically discussing state-of-the-art empirical findings, identifying methodological problems and proposing novel approaches.This article is part of the theme issue 'Perceptual consciousness and cognitive access'.}, } @article {pmid30061424, year = {2018}, author = {Li, K and Brant, CO and Huertas, M and Hessler, EJ and Mezei, G and Scott, AM and Hoye, TR and Li, W}, title = {Fatty-acid derivative acts as a sea lamprey migratory pheromone.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8603-8608}, pmid = {30061424}, issn = {1091-6490}, support = {R01 GM065597/GM/NIGMS NIH HHS/United States ; }, mesh = {Animal Migration/*drug effects/physiology ; Animals ; *Fatty Acids/chemistry/pharmacology ; Lampreys/*physiology ; *Pheromones/chemistry/pharmacology ; }, abstract = {Olfactory cues provide critical information for spatial orientation of fish, especially in the context of anadromous migrations. Born in freshwater, juveniles of anadromous fish descend to the ocean where they grow into adults before migrating back into freshwater to spawn. The reproductive migrants, therefore, are under selective pressures to locate streams optimal for offspring survival. Many anadromous fish use olfactory cues to orient toward suitable streams. However, no behaviorally active compounds have been identified as migratory cues. Extensive studies have shown that the migratory adult sea lampreys (Petromyzon marinus), a jawless fish, track a pheromone emitted by their stream-dwelling larvae, and, consequently, enter streams with abundant larvae. We fractionated extracts of larval sea lamprey washings with guidance from a bioassay that measures in-stream migratory behaviors of adults and identified four dihydroxylated tetrahydrofuran fatty acids, of which (+)-(2S,3S,5R)-tetrahydro-3-hydroxy-5-[(1R)-1-hydroxyhexyl]-2-furanoctanoic acid was shown as a migratory pheromone. The chemical structure was elucidated by spectroscopies and confirmed by chemical synthesis and X-ray crystallography. The four fatty acids were isomer-specific and enantiomer-specific in their olfactory and behavioral activities. A synthetic copy of the identified pheromone was a potent stimulant of the adult olfactory epithelium, and, at 5 × 10-13 M, replicated the extracts of larval washings in biasing adults into a tributary stream. Our results reveal a pheromone that bridges two distinct life stages and guides orientation over a large space that spans two different habitats. The identified molecule may be useful for control of the sea lamprey.}, } @article {pmid30061423, year = {2018}, author = {Shen, J}, title = {Zooming in on a small multidrug transporter reveals details of asymmetric protonation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8060-8062}, pmid = {30061423}, issn = {1091-6490}, support = {R01 GM098818/GM/NIGMS NIH HHS/United States ; R01 GM118772/GM/NIGMS NIH HHS/United States ; }, mesh = {*Membrane Transport Proteins ; *Protein Conformation ; }, } @article {pmid30061422, year = {2018}, author = {Yang, Y and Jang, GB and Yang, X and Wang, Q and He, S and Li, S and Quach, C and Zhao, S and Li, F and Yuan, Z and Lee, HR and Zhong, H and Liang, C}, title = {Central role of autophagic UVRAG in melanogenesis and the suntan response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7728-E7737}, pmid = {30061422}, issn = {1091-6490}, support = {R01 AI073099/AI/NIAID NIH HHS/United States ; R01 CA140964/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; HEK293 Cells ; Humans ; Melanins/*biosynthesis/genetics ; Melanoma/genetics/metabolism ; Melanosomes/genetics/*metabolism ; Microphthalmia-Associated Transcription Factor/genetics/metabolism ; Proto-Oncogene Proteins B-raf/genetics/metabolism ; Skin Pigmentation/*radiation effects ; Tumor Suppressor Proteins/genetics/*metabolism ; *Ultraviolet Rays ; Zebrafish/genetics/metabolism ; Zebrafish Proteins/genetics/metabolism ; }, abstract = {UV-induced cell pigmentation represents an important mechanism against skin cancers. Sun-exposed skin secretes α-MSH, which induces the lineage-specific transcriptional factor MITF and activates melanogenesis in melanocytes. Here, we show that the autophagic tumor suppressor UVRAG plays an integral role in melanogenesis by interaction with the biogenesis of lysosome-related organelles complex 1 (BLOC-1). This interaction is required for BLOC-1 stability and for BLOC-1-mediated cargo sorting and delivery to melanosomes. Absence of UVRAG dispersed BLOC-1 distribution and activity, resulting in impaired melanogenesis in vitro and defective melanocyte development in zebrafish in vivo. Furthermore, our results establish UVRAG as an important effector for melanocytes' response to α-MSH signaling as a direct target of MITF and reveal the molecular basis underlying the association between oncogenic BRAF and compromised UV protection in melanoma.}, } @article {pmid30061421, year = {2018}, author = {Lim, B and Fukaya, T and Heist, T and Levine, M}, title = {Temporal dynamics of pair-rule stripes in living Drosophila embryos.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8376-8381}, pmid = {30061421}, issn = {1091-6490}, support = {R35 GM118147/GM/NIGMS NIH HHS/United States ; T32 HG003284/HG/NHGRI NIH HHS/United States ; U01 EB021239/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; DNA-Binding Proteins/*genetics ; Drosophila/*embryology/genetics ; Drosophila Proteins/*genetics ; Embryo, Nonmammalian/physiology ; Enhancer Elements, Genetic/physiology ; Gene Editing ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Homeodomain Proteins/*genetics ; Transcription Factors/*genetics ; }, abstract = {Traditional studies of gene regulation in the Drosophila embryo centered primarily on the analysis of fixed tissues. These methods provided considerable insight into the spatial control of gene activity, such as the borders of eve stripe 2, but yielded only limited information about temporal dynamics. The advent of quantitative live-imaging and genome-editing methods permits the detailed examination of the temporal control of endogenous gene activity. Here, we present evidence that the pair-rule genes fushi tarazu (ftz) and even-skipped (eve) undergo dynamic shifts in gene expression. We observe sequential anterior shifting of the stripes along the anterior to posterior axis, with stripe 1 exhibiting movement before stripe 2 and the more posterior stripes. Conversely, posterior stripes shift over greater distances (two or three nuclei) than anterior stripes (one or two nuclei). Shifting of the ftz and eve stripes are slightly offset, with ftz moving faster than eve This observation is consistent with previous genetic studies, suggesting that eve is epistatic to ftz The precision of pair-rule temporal dynamics might depend on enhancer-enhancer interactions within the eve locus, since removal of the endogenous eve stripe 1 enhancer via CRISPR/Cas9 genome editing led to precocious and expanded expression of eve stripe 2. These observations raise the possibility of an added layer of complexity in the positional information encoded by the segmentation gene regulatory network.}, } @article {pmid30061420, year = {2018}, author = {Nakamura, A and Nambu, T and Ebara, S and Hasegawa, Y and Toyoshima, K and Tsuchiya, Y and Tomita, D and Fujimoto, J and Kurasawa, O and Takahara, C and Ando, A and Nishigaki, R and Satomi, Y and Hata, A and Hara, T}, title = {Inhibition of GCN2 sensitizes ASNS-low cancer cells to asparaginase by disrupting the amino acid response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7776-E7785}, pmid = {30061420}, issn = {1091-6490}, mesh = {Amino Acids/genetics/*metabolism ; Asparaginase/*pharmacology ; Aspartate-Ammonia Ligase/genetics/*metabolism ; Cell Line, Tumor ; Humans ; Neoplasm Proteins/*antagonists & inhibitors/genetics/*metabolism ; Neoplasms/*drug therapy/enzymology/genetics/pathology ; Protein Kinase Inhibitors/*pharmacology ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/genetics/metabolism ; }, abstract = {General control nonderepressible 2 (GCN2) plays a major role in the cellular response to amino acid limitation. Although maintenance of amino acid homeostasis is critical for tumor growth, the contribution of GCN2 to cancer cell survival and proliferation is poorly understood. In this study, we generated GCN2 inhibitors and demonstrated that inhibition of GCN2 sensitizes cancer cells with low basal-level expression of asparagine synthetase (ASNS) to the antileukemic agent l-asparaginase (ASNase) in vitro and in vivo. We first tested acute lymphoblastic leukemia (ALL) cells and showed that treatment with GCN2 inhibitors rendered ALL cells sensitive to ASNase by preventing the induction of ASNS, resulting in reduced levels of de novo protein synthesis. Comprehensive gene-expression profiling revealed that combined treatment with ASNase and GCN2 inhibitors induced the stress-activated MAPK pathway, thereby triggering apoptosis. By using cell-panel analyses, we also showed that acute myelogenous leukemia and pancreatic cancer cells were highly sensitive to the combined treatment. Notably, basal ASNS expression at protein levels was significantly correlated with sensitivity to combined treatment. These results provide mechanistic insights into the role of GCN2 in the amino acid response and a rationale for further investigation of GCN2 inhibitors for the treatment of cancer.}, } @article {pmid30061419, year = {2018}, author = {Hauge, KE and Brekke, KA and Nyborg, K and Lind, JT}, title = {Sustaining cooperation through self-sorting: The good, the bad, and the conditional.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1802875115}, pmid = {30061419}, issn = {1091-6490}, abstract = {In four public-good game experiments, we study self-sorting as a means to facilitate cooperation in groups. When individuals can choose to join groups precommitted to charity, such groups sustain cooperation toward the group's local public good. By eliciting subjects' conditional contribution profiles, we find that subjects who prefer the charity groups have higher average conditional contribution levels but do not differ with respect to the slope of their profiles. The majority of subjects in both group types are conditional cooperators whose willingness to contribute is stimulated by generous group members but undermined by free-riders. Charity groups thus seem better able to sustain cooperation because they attract a greater number of more generous individuals, triggering generous responses by conditional cooperators.}, } @article {pmid30061418, year = {2018}, author = {Cohen, SE and McKnight, BM and Golden, SS}, title = {Roles for ClpXP in regulating the circadian clock in Synechococcus elongatus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7805-E7813}, pmid = {30061418}, issn = {1091-6490}, support = {R35 GM118290/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Circadian Rhythm/*physiology ; Endopeptidase Clp/genetics/*metabolism ; Molecular Chaperones/genetics/*metabolism ; Protein Unfolding ; Synechococcus/*enzymology/genetics ; }, abstract = {In cyanobacteria, the KaiABC posttranslational oscillator drives circadian rhythms of gene expression and controls the timing of cell division. The Kai-based oscillator can be reconstituted in vitro, demonstrating that the clock can run without protein synthesis and degradation; however, protein degradation is known to be important for clock function in vivo. Here, we report that strains deficient in the ClpXP1P2 protease have, in addition to known long-period circadian rhythms, an exaggerated ability to synchronize with the external environment (reduced "jetlag") compared with WT strains. Deletion of the ClpX chaperone, but not the protease subunits ClpP1 or ClpP2, results in cell division defects in a manner that is dependent on the expression of a dusk-peaking factor. We propose that chaperone activities of ClpX are required to coordinate clock control of cell division whereas the protease activities of the ClpXP1P2 complex are required to maintain appropriate periodicity of the clock and its synchronization with the external environment.}, } @article {pmid30061417, year = {2018}, author = {Mullen, RD and Wang, Y and Liu, B and Moore, EL and Behringer, RR}, title = {Osterix functions downstream of anti-Müllerian hormone signaling to regulate Müllerian duct regression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8382-8387}, pmid = {30061417}, issn = {1091-6490}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R37 HD030284/HD/NICHD NIH HHS/United States ; T32 CA009299/CA/NCI NIH HHS/United States ; R01 HD030284/HD/NICHD NIH HHS/United States ; S10 OD024976/OD/NIH HHS/United States ; }, mesh = {Animals ; Anti-Mullerian Hormone/*physiology ; Gene Expression Profiling ; Male ; Mice ; Mice, Inbred C57BL ; Mullerian Ducts/*physiology ; Signal Transduction/*physiology ; Sp7 Transcription Factor/*physiology ; beta Catenin/physiology ; }, abstract = {In mammals, the developing reproductive tract primordium of male and female fetuses consists of the Wolffian duct and the Müllerian duct (MD), two epithelial tube pairs surrounded by mesenchyme. During male development, mesenchyme-epithelia interactions mediate MD regression to prevent its development into a uterus, oviduct, and upper vagina. It is well established that transforming growth factor-β family member anti-Müllerian hormone (AMH) secreted from the fetal testis and its type 1 and 2 receptors expressed in MD mesenchyme regulate MD regression. However, little is known about the molecular network regulating downstream actions of AMH signaling. To identify potential AMH-induced genes and regulatory networks controlling MD regression in a global nonbiased manner, we examined transcriptome differences in MD mesenchyme between males (AMH signaling on) and females (AMH signaling off) by RNA-seq analysis of purified fetal MD mesenchymal cells. This analysis found 82 genes up-regulated in males during MD regression and identified Osterix (Osx)/Sp7, a key transcriptional regulator of osteoblast differentiation and bone formation, as a downstream effector of AMH signaling during MD regression. Osx/OSX was expressed in a male-specific pattern in MD mesenchyme during MD regression. OSX expression was lost in mutant males without AMH signaling. In addition, transgenic mice ectopically expressing human AMH in females induced a male pattern of Osx expression. Together, these results indicate that AMH signaling is necessary and sufficient for Osx expression in the MD mesenchyme. In addition, MD regression was delayed in Osx-null males, identifying Osx as a factor that regulates MD regression.}, } @article {pmid30061416, year = {2018}, author = {Le, C and Wu, X and Qin, S and Li, Y and Thomale, R and Zhang, FC and Hu, J}, title = {Dirac semimetal in β-CuI without surface Fermi arcs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8311-8315}, pmid = {30061416}, issn = {1091-6490}, abstract = {Anomalous surface states with Fermi arcs are commonly considered to be a fingerprint of Dirac semimetals (DSMs). In contrast to Weyl semimetals, however, Fermi arcs of DSMs are not topologically protected. Using first-principles calculations, we predict that β-cuprous iodide (β-CuI) is a peculiar DSM whose surface states form closed Fermi pockets instead of Fermi arcs. In such a fermiological Dirac semimetal, the deformation mechanism from Fermi arcs to Fermi pockets stems from a large cubic term preserving all crystal symmetries and from the small energy difference between the surface and bulk Dirac points. The cubic term in β-CuI, usually negligible in prototypical DSMs, becomes relevant because of the particular crystal structure. As such, we establish a concrete material example manifesting the lack of topological protection for surface Fermi arcs in DSMs.}, } @article {pmid30061415, year = {2018}, author = {Kayama, H and Kohyama, M and Okuzaki, D and Motooka, D and Barman, S and Okumura, R and Muneta, M and Hoshino, K and Sasaki, I and Ise, W and Matsuno, H and Nishimura, J and Kurosaki, T and Nakamura, S and Arase, H and Kaisho, T and Takeda, K}, title = {Heme ameliorates dextran sodium sulfate-induced colitis through providing intestinal macrophages with noninflammatory profiles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8418-8423}, pmid = {30061415}, issn = {1091-6490}, mesh = {Animals ; CX3C Chemokine Receptor 1/physiology ; Colitis/*drug therapy ; Cytokines/biosynthesis ; DNA-Binding Proteins/physiology ; Dextran Sulfate/toxicity ; Heme/*pharmacology ; Intestines/*immunology ; Iron, Dietary/administration & dosage ; Macrophages/*immunology ; Mice ; Mice, Inbred C57BL ; Toll-Like Receptors/physiology ; Transcription Factor RelA/physiology ; }, abstract = {The local environment is crucial for shaping the identities of tissue-resident macrophages (Mϕs). When hemorrhage occurs in damaged tissues, hemoglobin induces differentiation of anti-inflammatory Mϕs with reparative function. Mucosal bleeding is one of the pathological features of inflammatory bowel diseases. However, the heme-mediated mechanism modulating activation of intestinal innate immune cells remains poorly understood. Here, we show that heme regulates gut homeostasis through induction of Spi-C in intestinal CX3CR1high Mϕs. Intestinal CX3CR1high Mϕs highly expressed Spi-C in a heme-dependent manner, and myeloid lineage-specific Spic-deficient (Lyz2-cre; Spicflox/flox) mice showed severe intestinal inflammation with an increased number of Th17 cells during dextran sodium sulfate-induced colitis. Spi-C down-regulated the expression of a subset of Toll-like receptor (TLR)-inducible genes in intestinal CX3CR1high Mϕs to prevent colitis. LPS-induced production of IL-6 and IL-1α, but not IL-10 and TNF-α, by large intestinal Mϕs from Lyz2-cre; Spicflox/flox mice was markedly enhanced. The interaction of Spi-C with IRF5 was linked to disruption of the IRF5-NF-κB p65 complex formation, thereby abrogating recruitment of IRF5 and NF-κB p65 to the Il6 and Il1a promoters. Collectively, these results demonstrate that heme-mediated Spi-C is a key molecule for the noninflammatory signature of intestinal Mϕs by suppressing the induction of a subset of TLR-inducible genes through binding to IRF5.}, } @article {pmid30061414, year = {2018}, author = {Grither, WR and Longmore, GD}, title = {Inhibition of tumor-microenvironment interaction and tumor invasion by small-molecule allosteric inhibitor of DDR2 extracellular domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7786-E7794}, pmid = {30061414}, issn = {1091-6490}, support = {R01 CA196205/CA/NCI NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; U54 CA210173/CA/NCI NIH HHS/United States ; }, mesh = {Allosteric Regulation/drug effects/genetics ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Breast Neoplasms/*drug therapy/enzymology/genetics/pathology ; Discoidin Domain Receptor 2/*antagonists & inhibitors/genetics/metabolism ; Female ; Fibroblasts/enzymology/pathology ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Transgenic ; Neoplasm Invasiveness/genetics ; Neoplasm Proteins/*antagonists & inhibitors/genetics/metabolism ; Protein Kinase Inhibitors/chemistry/*pharmacology ; Signal Transduction/*drug effects/genetics ; Tumor Microenvironment/*drug effects/genetics ; }, abstract = {The action of the collagen binding receptor tyrosine kinase (RTK) discoidin domain receptor 2 (DDR2) in both tumor and tumor stromal cells has been established as critical for breast cancer metastasis. Small molecule inhibitors that target the extracellular domain of RTKs are rare, as they have classically been regarded as too small to block binding with large polypeptide ligands. Here, we report the identification and characterization of a selective, extracellularly acting small molecule inhibitor (WRG-28) of DDR2 that uniquely inhibits receptor-ligand interactions via allosteric modulation of the receptor. By targeting DDR2, WRG-28 inhibits tumor invasion and migration, as well as tumor-supporting roles of the stroma, and inhibits metastatic breast tumor cell colonization in the lungs. These findings represent an approach to inhibiting tumor-stromal interactions and support the development of allosteric inhibitors of DDR2, such as WRG-28, as a promising approach to antimetastasis treatment.}, } @article {pmid30061413, year = {2018}, author = {Gao, X and Yu, H and Sáez, I and Blue, PR and Zhu, L and Hsu, M and Zhou, X}, title = {Distinguishing neural correlates of context-dependent advantageous- and disadvantageous-inequity aversion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7680-E7689}, pmid = {30061413}, issn = {1091-6490}, mesh = {Cerebral Cortex/*physiology ; Computer Simulation ; Decision Making ; Female ; Games, Experimental ; Humans ; Male ; *Social Behavior ; }, abstract = {Humans can integrate social contextual information into decision-making processes to adjust their responses toward inequity. This context dependency emerges when individuals receive more (i.e., advantageous inequity) or less (i.e., disadvantageous inequity) than others. However, it is not clear whether context-dependent processing of advantageous and disadvantageous inequity involves differential neurocognitive mechanisms. Here, we used fMRI to address this question by combining an interactive game that modulates social contexts (e.g., interpersonal guilt) with computational models that enable us to characterize individual weights on inequity aversion. In each round, the participant played a dot estimation task with an anonymous coplayer. The coplayer would receive pain stimulation with 50% probability when either of them responded incorrectly. At the end of each round, the participant completed a variant of dictator game, which determined payoffs for him/herself and the coplayer. Computational modeling demonstrated the context dependency of inequity aversion: when causing pain to the coplayer (i.e., guilt context), participants cared more about the advantageous inequity and became more tolerant of the disadvantageous inequity, compared with other conditions. Consistently, neuroimaging results suggested the two types of inequity were associated with differential neurocognitive substrates. While the context-dependent processing of advantageous inequity was associated with social- and mentalizing-related processes, involving left anterior insula, right dorsolateral prefrontal cortex, and dorsomedial prefrontal cortex, the context-dependent processing of disadvantageous inequity was primarily associated with emotion- and conflict-related processes, involving left posterior insula, right amygdala, and dorsal anterior cingulate cortex. These results extend our understanding of decision-making processes related to inequity aversion.}, } @article {pmid30061412, year = {2018}, author = {Abe, T and Ooka, M and Kawasumi, R and Miyata, K and Takata, M and Hirota, K and Branzei, D}, title = {Warsaw breakage syndrome DDX11 helicase acts jointly with RAD17 in the repair of bulky lesions and replication through abasic sites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8412-8417}, pmid = {30061412}, issn = {1091-6490}, support = {242928//European Research Council/International ; }, mesh = {Animals ; Cell Cycle Proteins/*physiology ; Chickens ; DEAD-box RNA Helicases/*physiology ; DNA Helicases/*physiology ; *DNA Repair ; *DNA Replication ; Fanconi Anemia/genetics ; Genomic Instability ; Homologous Recombination ; Humans ; Somatic Hypermutation, Immunoglobulin ; }, abstract = {Warsaw breakage syndrome, a developmental disorder caused by mutations in the DDX11/ChlR1 helicase, shows cellular features of genome instability similar to Fanconi anemia (FA). Here we report that DDX11-deficient avian DT40 cells exhibit interstrand crosslink (ICL)-induced chromatid breakage, with DDX11 functioning as backup for the FA pathway in regard to ICL repair. Importantly, we establish that DDX11 acts jointly with the 9-1-1 checkpoint clamp and its loader, RAD17, primarily in a postreplicative fashion, to promote homologous recombination repair of bulky lesions, but is not required for intra-S checkpoint activation or efficient fork progression. Notably, we find that DDX11 also promotes diversification of the chicken Ig-variable gene, a process triggered by programmed abasic sites, by facilitating both hypermutation and homeologous recombination-mediated gene conversion. Altogether, our results uncover that DDX11 orchestrates jointly with 9-1-1 and its loader, RAD17, DNA damage tolerance at sites of bulky lesions, and endogenous abasic sites. These functions may explain the essential roles of DDX11 and its similarity with 9-1-1 during development.}, } @article {pmid30061411, year = {2018}, author = {Joseph, DB and Chandrashekar, AS and Abler, LL and Chu, LF and Thomson, JA and Mendelsohn, C and Vezina, CM}, title = {In vivo replacement of damaged bladder urothelium by Wolffian duct epithelial cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8394-8399}, pmid = {30061411}, issn = {1091-6490}, support = {R01 DK099328/DK/NIDDK NIH HHS/United States ; U01 DK110807/DK/NIDDK NIH HHS/United States ; R01 DK095044/DK/NIDDK NIH HHS/United States ; U54 DK104309/DK/NIDDK NIH HHS/United States ; U54 DK104310/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Apoptosis ; Cell Lineage ; DNA (Cytosine-5-)-Methyltransferase 1/physiology ; DNA Damage ; DNA Methylation ; Epithelial Cells/physiology ; Mice ; Regeneration ; Urinary Bladder/*physiology ; Urothelium/*physiology ; Wolffian Ducts/*physiology ; }, abstract = {The bladder's remarkable regenerative capacity had been thought to derive exclusively from its own progenitors. While examining consequences of DNA methyltransferase 1 (Dnmt1) inactivation in mouse embryonic bladder epithelium, we made the surprising discovery that Wolffian duct epithelial cells can support bladder regeneration. Conditional Dnmt1 inactivation in mouse urethral and bladder epithelium triggers widespread apoptosis, depletes basal and intermediate bladder cells, and disrupts uroplakin protein expression. These events coincide with Wolffian duct epithelial cell recruitment into Dnmt1 mutant urethra and bladder where they are reprogrammed to express bladder markers, including FOXA1, keratin 5, P63, and uroplakin. This is evidence that Wolffian duct epithelial cells are summoned in vivo to replace damaged bladder epithelium and function as a reservoir of cells for bladder regeneration.}, } @article {pmid30061410, year = {2018}, author = {Yoon, JS and Mogilicherla, K and Gurusamy, D and Chen, X and Chereddy, SCRR and Palli, SR}, title = {Double-stranded RNA binding protein, Staufen, is required for the initiation of RNAi in coleopteran insects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8334-8339}, pmid = {30061410}, issn = {1091-6490}, support = {R01 GM070559/GM/NIGMS NIH HHS/United States ; R21 AI131427/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Coleoptera/*genetics ; Insect Proteins/*physiology ; *RNA Interference ; RNA, Double-Stranded/*metabolism ; RNA-Binding Proteins/genetics/*physiology ; }, abstract = {RNA interference (RNAi) is being used to develop methods to control pests and disease vectors. RNAi is robust and systemic in coleopteran insects but is quite variable in other insects. The determinants of efficient RNAi in coleopterans, as well as its potential mechanisms of resistance, are not known. RNAi screen identified a double-stranded RNA binding protein (StaufenC) as a major player in RNAi. StaufenC homologs have been identified in only coleopteran insects. Experiments in two coleopteran insects, Leptinotarsa decemlineata and Tribolium castaneum, showed the requirement of StaufenC for RNAi, especially for processing of double-stranded RNA (dsRNA) to small interfering RNA. RNAi-resistant cells were selected by exposing L. decemlineata, Lepd-SL1 cells to the inhibitor of apoptosis 1 dsRNA for multiple generations. The resistant cells showed lower levels of StaufenC expression compared with its expression in susceptible cells. These studies showed that coleopteran-specific StaufenC is required for RNAi and is a potential target for RNAi resistance. The data included in this article will help improve RNAi in noncoleopteran insects and manage RNAi resistance in coleopteran insects.}, } @article {pmid30061409, year = {2018}, author = {Wu, L and Liu, Q and Li, Y}, title = {Prevalence of tornado-scale vortices in the tropical cyclone eyewall.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8307-8310}, pmid = {30061409}, issn = {1091-6490}, abstract = {Analyses of datasets from manned research flights that penetrated hurricane eyes and tropical cyclone (TC) damage surveys strongly suggest the existence of tornado-scale vortices in the turbulent boundary layer of the TC eyewall. However, their small horizontal scale, their fast movement, and the associated severe turbulence make the tornado-scale vortex very difficult to observe directly. To understand tornado-scale vortices in the TC eyewall and their influence on the TC vortex, mesoscale rainbands, and convective clouds, a numerical experiment including seven nested domains with the smallest horizontal grid interval of 37 m is conducted to perform a large eddy simulation (LES) with the Advanced Weather Research and Forecast (WRF) model. We show that most of the observed features associated with tornado-scale vortices can be realistically simulated in the WRF-LES framework. The numerical simulation confirms the existence of simulated tornado-scale vortices in the turbulent boundary layer of the TC eyewall. Our numerical experiment suggests that tornado-scale vortices are prevalent at the inner edge of the intense eyewall convection.}, } @article {pmid30061408, year = {2018}, author = {Tunnacliffe, E and Corrigan, AM and Chubb, JR}, title = {Promoter-mediated diversification of transcriptional bursting dynamics following gene duplication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8364-8369}, pmid = {30061408}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 202867/Z/16/Z//Wellcome Trust/United Kingdom ; MC_U12266B//Medical Research Council/United Kingdom ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Actins/*genetics ; Cell Line ; Dictyostelium/*genetics ; *Gene Duplication ; Gene Expression Regulation ; *Promoter Regions, Genetic ; *Transcription, Genetic ; }, abstract = {During the evolution of gene families, functional diversification of proteins often follows gene duplication. However, many gene families expand while preserving protein sequence. Why do cells maintain multiple copies of the same gene? Here we have addressed this question for an actin family with 17 genes encoding an identical protein. The genes have divergent flanking regions and are scattered throughout the genome. Surprisingly, almost the entire family showed similar developmental expression profiles, with their expression also strongly coupled in single cells. Using live cell imaging, we show that differences in gene expression were apparent over shorter timescales, with family members displaying different transcriptional bursting dynamics. Strong "bursty" behaviors contrasted steady, more continuous activity, indicating different regulatory inputs to individual actin genes. To determine the sources of these different dynamic behaviors, we reciprocally exchanged the upstream regulatory regions of gene family members. This revealed that dynamic transcriptional behavior is directly instructed by upstream sequence, rather than features specific to genomic context. A residual minor contribution of genomic context modulates the gene OFF rate. Our data suggest promoter diversification following gene duplication could expand the range of stimuli that regulate the expression of essential genes. These observations contextualize the significance of transcriptional bursting.}, } @article {pmid30061407, year = {2018}, author = {Nagano, H and Hashimoto, N and Nakayama, A and Suzuki, S and Miyabayashi, Y and Yamato, A and Higuchi, S and Fujimoto, M and Sakuma, I and Beppu, M and Yokoyama, M and Suzuki, Y and Sugano, S and Ikeda, K and Tatsuno, I and Manabe, I and Yokote, K and Inoue, S and Tanaka, T}, title = {p53-inducible DPYSL4 associates with mitochondrial supercomplexes and regulates energy metabolism in adipocytes and cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8370-8375}, pmid = {30061407}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/biosynthesis ; Adipocytes/*metabolism ; Animals ; Cell Line, Tumor ; *Energy Metabolism ; Humans ; Male ; Mice ; Mice, SCID ; Mitochondria/*metabolism ; Neoplasms/*metabolism ; Nerve Tissue Proteins/*physiology ; Obesity/metabolism ; Oxygen Consumption ; Tumor Suppressor Protein p53/*physiology ; Tumor Suppressor Proteins/physiology ; }, abstract = {The tumor suppressor p53 regulates multiple cellular functions, including energy metabolism. Metabolic deregulation is implicated in the pathogenesis of some cancers and in metabolic disorders and may result from the inactivation of p53 functions. Using RNA sequencing and ChIP sequencing of cancer cells and preadipocytes, we demonstrate that p53 modulates several metabolic processes via the transactivation of energy metabolism genes including dihydropyrimidinase-like 4 (DPYSL4). DPYSL4 is a member of the collapsin response mediator protein family, which is involved in cancer invasion and progression. Intriguingly, DPYSL4 overexpression in cancer cells and preadipocytes up-regulated ATP production and oxygen consumption, while DPYSL4 knockdown using siRNA or CRISPR/Cas9 down-regulated energy production. Furthermore, DPYSL4 was associated with mitochondrial supercomplexes, and deletion of its dihydropyrimidinase-like domain abolished its association and its ability to stimulate ATP production and suppress the cancer cell invasion. Mouse-xenograft and lung-metastasis models indicated that DPYSL4 expression compromised tumor growth and metastasis in vivo. Consistently, database analyses demonstrated that low DPYSL4 expression was significantly associated with poor survival of breast and ovarian cancers in accordance with its reduced expression in certain types of cancer tissues. Moreover, immunohistochemical analysis using the adipose tissue of obese patients revealed that DPYSL4 expression was positively correlated with INFg and body mass index in accordance with p53 activation. Together, these results suggest that DPYSL4 plays a key role in the tumor-suppressor function of p53 by regulating oxidative phosphorylation and the cellular energy supply via its association with mitochondrial supercomplexes, possibly linking to the pathophysiology of both cancer and obesity.}, } @article {pmid30061406, year = {2018}, author = {Dunn, BS and Rush, L and Lu, JY and Xu, T}, title = {Mutations in the Drosophila tricellular junction protein M6 synergize with RasV12 to induce apical cell delamination and invasion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8358-8363}, pmid = {30061406}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Movement ; Drosophila Proteins/genetics/*physiology ; Drosophila melanogaster/genetics ; Intercellular Junctions/*physiology ; *Mutation ; Myosin Type II/physiology ; *Neoplasm Invasiveness ; Neoplasm Metastasis ; ras Proteins/*physiology ; rhoA GTP-Binding Protein/physiology ; }, abstract = {Complications from metastasis are responsible for the majority of cancer-related deaths. Despite the outsized medical impact of metastasis, remarkably little is known about one of the key early steps of metastasis: departure of a tumor cell from its originating tissue. It is well documented that cellular delamination in the basal direction can induce invasive behaviors, but it remains unknown if apical cell delamination can induce migration and invasion in a cancer context. To explore this feature of cancer progression, we performed a genetic screen in Drosophila and discovered that mutations in the protein M6 synergize with oncogenic Ras to drive invasion following apical delamination without crossing a basement membrane. Mechanistically, we observed that M6-deficient RasV12 clones delaminate as a result of alterations in a Canoe-RhoA-myosin II axis that is necessary for both the delamination and invasion phenotypes. To uncover the cellular roles of M6, we show that it localizes to tricellular junctions in epithelial tissues where it is necessary for the structural integrity of multicellular contacts. This work provides evidence that apical delamination can precede invasion and highlights the important role that tricellular junction integrity can play in this process.}, } @article {pmid30061405, year = {2018}, author = {García-Palacios, P and Gross, N and Gaitán, J and Maestre, FT}, title = {Climate mediates the biodiversity-ecosystem stability relationship globally.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8400-8405}, pmid = {30061405}, issn = {1091-6490}, mesh = {*Biodiversity ; *Climate ; *Ecosystem ; }, abstract = {The insurance hypothesis, stating that biodiversity can increase ecosystem stability, has received wide research and political attention. Recent experiments suggest that climate change can impact how plant diversity influences ecosystem stability, but most evidence of the biodiversity-stability relationship obtained to date comes from local studies performed under a limited set of climatic conditions. Here, we investigate how climate mediates the relationships between plant (taxonomical and functional) diversity and ecosystem stability across the globe. To do so, we coupled 14 years of temporal remote sensing measurements of plant biomass with field surveys of diversity in 123 dryland ecosystems from all continents except Antarctica. Across a wide range of climatic and soil conditions, plant species pools, and locations, we were able to explain 73% of variation in ecosystem stability, measured as the ratio of the temporal mean biomass to the SD. The positive role of plant diversity on ecosystem stability was as important as that of climatic and soil factors. However, we also found a strong climate dependency of the biodiversity-ecosystem stability relationship across our global aridity gradient. Our findings suggest that the diversity of leaf traits may drive ecosystem stability at low aridity levels, whereas species richness may have a greater stabilizing role under the most arid conditions evaluated. Our study highlights that to minimize variations in the temporal delivery of ecosystem services related to plant biomass, functional and taxonomic plant diversity should be particularly promoted under low and high aridity conditions, respectively.}, } @article {pmid30061404, year = {2018}, author = {Warren, JS and Tracy, CM and Miller, MR and Makaju, A and Szulik, MW and Oka, SI and Yuzyuk, TN and Cox, JE and Kumar, A and Lozier, BK and Wang, L and Llana, JG and Sabry, AD and Cawley, KM and Barton, DW and Han, YH and Boudina, S and Fiehn, O and Tucker, HO and Zaitsev, AV and Franklin, S}, title = {Histone methyltransferase Smyd1 regulates mitochondrial energetics in the heart.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7871-E7880}, pmid = {30061404}, issn = {1091-6490}, support = {R01 HL130424/HL/NHLBI NIH HHS/United States ; R01 CA031534/CA/NCI NIH HHS/United States ; P30 DK020579/DK/NIDDK NIH HHS/United States ; S10 OD021505/OD/NIH HHS/United States ; T35 DK103596/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; DNA-Binding Proteins/genetics/*metabolism ; Energy Metabolism/*physiology ; Gene Expression Regulation ; Histone Methyltransferases ; Histone-Lysine N-Methyltransferase/genetics/*metabolism ; Mice ; Mice, Knockout ; Mitochondria, Heart/genetics/*metabolism ; Muscle Proteins/genetics/*metabolism ; Myocardium/*enzymology ; PPAR alpha/biosynthesis/genetics ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/*biosynthesis/genetics ; Retinoid X Receptor alpha/biosynthesis/genetics ; Transcription Factors/genetics/*metabolism ; }, abstract = {Smyd1, a muscle-specific histone methyltransferase, has established roles in skeletal and cardiac muscle development, but its role in the adult heart remains poorly understood. Our prior work demonstrated that cardiac-specific deletion of Smyd1 in adult mice (Smyd1-KO) leads to hypertrophy and heart failure. Here we show that down-regulation of mitochondrial energetics is an early event in these Smyd1-KO mice preceding the onset of structural abnormalities. This early impairment of mitochondrial energetics in Smyd1-KO mice is associated with a significant reduction in gene and protein expression of PGC-1α, PPARα, and RXRα, the master regulators of cardiac energetics. The effect of Smyd1 on PGC-1α was recapitulated in primary cultured rat ventricular myocytes, in which acute siRNA-mediated silencing of Smyd1 resulted in a greater than twofold decrease in PGC-1α expression without affecting that of PPARα or RXRα. In addition, enrichment of histone H3 lysine 4 trimethylation (a mark of gene activation) at the PGC-1α locus was markedly reduced in Smyd1-KO mice, and Smyd1-induced transcriptional activation of PGC-1α was confirmed by luciferase reporter assays. Functional confirmation of Smyd1's involvement showed an increase in mitochondrial respiration capacity induced by overexpression of Smyd1, which was abolished by siRNA-mediated PGC-1α knockdown. Conversely, overexpression of PGC-1α rescued transcript expression and mitochondrial respiration caused by silencing Smyd1 in cardiomyocytes. These findings provide functional evidence for a role of Smyd1, or any member of the Smyd family, in regulating cardiac energetics in the adult heart, which is mediated, at least in part, via modulating PGC-1α.}, } @article {pmid30061403, year = {2018}, author = {}, title = {Correction for Otto et al., Past role and future outlook of the Conservation Reserve Program for supporting honey bees in the Great Plains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7651}, doi = {10.1073/pnas.1812119115}, pmid = {30061403}, issn = {1091-6490}, } @article {pmid30061402, year = {2018}, author = {Lynagh, T and Mikhaleva, Y and Colding, JM and Glover, JC and Pless, SA}, title = {Acid-sensing ion channels emerged over 600 Mya and are conserved throughout the deuterostomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8430-8435}, pmid = {30061402}, issn = {1091-6490}, mesh = {Acid Sensing Ion Channels/*physiology ; Animals ; Chordata/*physiology ; Hydrogen Bonding ; Hydrogen-Ion Concentration ; Mice ; Phylogeny ; Protein Isoforms ; }, abstract = {Acid-sensing ion channels (ASICs) are proton-gated ion channels broadly expressed in the vertebrate nervous system, converting decreased extracellular pH into excitatory sodium current. ASICs were previously thought to be a vertebrate-specific branch of the DEG/ENaC family, a broadly conserved but functionally diverse family of channels. Here, we provide phylogenetic and experimental evidence that ASICs are conserved throughout deuterostome animals, showing that ASICs evolved over 600 million years ago. We also provide evidence of ASIC expression in the central nervous system of the tunicate, Oikopleura dioica Furthermore, by comparing broadly related ASICs, we identify key molecular determinants of proton sensitivity and establish that proton sensitivity of the ASIC4 isoform was lost in the mammalian lineage. Taken together, these results suggest that contributions of ASICs to neuronal function may also be conserved broadly in numerous animal phyla.}, } @article {pmid30061401, year = {2018}, author = {}, title = {Correction for Daniel et al., Mechanistic insights in transcription-coupled nucleotide excision repair of ribosomal DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7650}, doi = {10.1073/pnas.1812123115}, pmid = {30061401}, issn = {1091-6490}, } @article {pmid30061400, year = {2018}, author = {Li, X and Jiang, Y and Chong, S and Walt, DR}, title = {Bottom-up single-molecule strategy for understanding subunit function of tetrameric β-galactosidase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8346-8351}, pmid = {30061400}, issn = {1091-6490}, mesh = {Kinetics ; Plasmids ; Polymorphism, Single Nucleotide ; Protein Biosynthesis ; *Protein Multimerization ; Protein Subunits/*physiology ; beta-Galactosidase/biosynthesis/chemistry/genetics/*physiology ; }, abstract = {In this paper, we report an example of the engineered expression of tetrameric β-galactosidase (β-gal) containing varying numbers of active monomers. Specifically, by combining wild-type and single-nucleotide polymorphism plasmids at varying ratios, tetrameric β-gal was expressed in vitro with one to four active monomers. The kinetics of individual enzyme molecules revealed four distinct populations, corresponding to the number of active monomers in the enzyme. Using single-molecule-level enzyme kinetics, we were able to measure an accurate in vitro mistranslation frequency (5.8 × 10-4 per base). In addition, we studied the kinetics of the mistranslated β-gal at the single-molecule level.}, } @article {pmid30061399, year = {2018}, author = {Nasca, C and Bigio, B and Lee, FS and Young, SP and Kautz, MM and Albright, A and Beasley, J and Millington, DS and Mathé, AA and Kocsis, JH and Murrough, JW and McEwen, BS and Rasgon, N}, title = {Acetyl-l-carnitine deficiency in patients with major depressive disorder.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8627-8632}, pmid = {30061399}, issn = {1091-6490}, mesh = {Acetylcarnitine/*blood/*deficiency ; Adult ; Age Factors ; Aged ; Carnitine/blood ; Depressive Disorder, Major/*blood ; Female ; Humans ; Male ; Middle Aged ; Sex Factors ; }, abstract = {The lack of biomarkers to identify target populations greatly limits the promise of precision medicine for major depressive disorder (MDD), a primary cause of ill health and disability. The endogenously produced molecule acetyl-l-carnitine (LAC) is critical for hippocampal function and several behavioral domains. In rodents with depressive-like traits, LAC levels are markedly decreased and signal abnormal hippocampal glutamatergic function and dendritic plasticity. LAC supplementation induces rapid and lasting antidepressant-like effects via epigenetic mechanisms of histone acetylation. This mechanistic model led us to evaluate LAC levels in humans. We found that LAC levels, and not those of free carnitine, were decreased in patients with MDD compared with age- and sex-matched healthy controls in two independent study centers. Secondary exploratory analyses showed that the degree of LAC deficiency reflected both the severity and age of onset of MDD. Moreover, these analyses showed that the decrease in LAC was larger in patients with a history of treatment-resistant depression (TRD), among whom childhood trauma and, specifically, a history of emotional neglect and being female, predicted the decreased LAC. These findings suggest that LAC may serve as a candidate biomarker to help diagnose a clinical endophenotype of MDD characterized by decreased LAC, greater severity, and earlier onset as well as a history of childhood trauma in patients with TRD. Together with studies in rodents, these translational findings support further exploration of LAC as a therapeutic target that may help to define individualized treatments in biologically based depression subtype consistent with the spirit of precision medicine.}, } @article {pmid30061398, year = {2018}, author = {Li, J and Song, X}, title = {Tearing of Indian mantle lithosphere from high-resolution seismic images and its implications for lithosphere coupling in southern Tibet.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8296-8300}, pmid = {30061398}, issn = {1091-6490}, abstract = {What happened to the Indian mantle lithosphere (IML) during the Indian-Eurasian collision and what role it has played on the plateau growth are fundamental questions that remain unanswered. Here, we show clear images of the IML from high-resolution P and S tomography, which suggest that the subducted IML is torn into at least four pieces with different angles and northern limits, shallower and extending further in the west and east sides while steeper in the middle. Intermediate-depth earthquakes in the lower crust and mantle are located almost exclusively in the high-velocity (and presumably strong) part of the Indian lithosphere. The tearing of the IML provides a unified mechanism for Late Miocene and Quaternary rifting, current crustal deformation, and intermediate-depth earthquakes in the southern and central Tibetan Plateau and suggests that the deformations of the crust and the mantle lithosphere are strongly coupled.}, } @article {pmid30061397, year = {2018}, author = {Liu, P and Fu, X and Zhu, J}, title = {Juvenile hormone-regulated alternative splicing of the taiman gene primes the ecdysteroid response in adult mosquitoes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7738-E7747}, pmid = {30061397}, issn = {1091-6490}, support = {R01 AI099250/AI/NIAID NIH HHS/United States ; }, mesh = {Aedes/genetics/*metabolism ; Alternative Splicing/*physiology ; Animals ; Ecdysterone/genetics/*metabolism ; Feeding Behavior/physiology ; Female ; Insect Proteins/*biosynthesis/genetics ; Juvenile Hormones/genetics/*metabolism ; Protein Isoforms/biosynthesis/genetics ; Transcription Factors/*biosynthesis/genetics ; Vitellogenesis/physiology ; }, abstract = {Juvenile hormone (JH) regulates many aspects of insect development and reproduction. In some processes, JH plays a critical role in defining the action of the steroid hormone 20-hydroxyecdysone (20E). In Aedes aegypti mosquitoes, JH prepares newly emerged female adults to become competent to synthesize vitellogenin in response to 20E after blood ingestion. The molecular basis of this competence is still not well understood. Here, we report that JH regulates pre-mRNA splicing of the taiman gene, which encodes a key transcriptional regulator required for both JH- and 20E-controlled gene expression. JH stimulated the production of the Taiman isoforms A/B, while reducing the levels of the isoforms C/D, in the fat body after adult eclosion. The appearance of the A/B isoforms in maturing mosquitoes was accompanied by acquisition of the competence to respond to 20E. Depletion of the A/B isoforms, by inhibiting the alternative splicing or by isoform-specific RNA interference, considerably diminished the 20E-induced gene expression after a blood meal and substantially impaired oocyte development. In accordance with this observation, further studies indicated that in the presence of 20E, the Taiman A/B isoforms showed much stronger interactions with the 20E receptor complex than the Taiman C/D isoforms. In contrast, all four isoforms displayed similar capabilities of forming active JH receptor complexes with the methoprene-tolerant protein (Met). This study suggested that JH confers the competence to newly emerged female mosquitoes by regulating mRNA splicing to generate the Taiman isoforms that are essential for the vitellogenic 20E response.}, } @article {pmid30061396, year = {2018}, author = {Sanger, MC and Hill, MA and Lattanzi, GD and Padgett, BD and Larsen, CS and Culleton, BJ and Kennett, DJ and Dussubieux, L and Napolitano, MF and Lacombe, S and Thomas, DH}, title = {Early metal use and crematory practices in the American Southeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7672-E7679}, pmid = {30061396}, issn = {1091-6490}, mesh = {*Archaeology ; *Copper ; *Cremation ; Georgia ; Humans ; South Carolina ; }, abstract = {Long-distance exchange of copper objects during the Archaic Period (ca. 8000-3000 cal B.P.) is a bellwether of emergent social complexity in the Eastern Woodlands. Originating from the Great Lakes, the Canadian Maritimes, and the Appalachian Mountains, Archaic-age copper is found in significant amounts as far south as Tennessee and in isolated pockets at major trade centers in Louisiana but is absent from most of the southeastern United States. Here we report the discovery of a copper band found with the cremated remains of at least seven individuals buried in the direct center of a Late Archaic shell ring located in coastal Georgia. Late Archaic shell rings are massive circular middens thought to be constructed, in part, during large-scale ritual gatherings and feasting events. The exotic copper and cremated remains are unique in coastal South Carolina and Georgia where Archaic-age cremations are conspicuously absent and no other Archaic copper objects have been reported. Elemental data produced through laser ablation inductively coupled plasma mass spectrometry shows the copper originated from the Great Lakes, effectively extending Archaic copper exchange almost 1,000 km beyond its traditional boundaries. Similarities in mortuary practices and the presence of copper originating from the Great Lakes reveal the presence of long-distance exchange relations spanning vast portions of the eastern United States and suggest an unexpected level of societal complexity at shell ring localities. These findings are consistent with the hypothesis that elite actors solidified their positions through ritual gatherings and the long-distance exchange of exotic objects during the Archaic.}, } @article {pmid30061395, year = {2018}, author = {Vaistij, FE and Barros-Galvão, T and Cole, AF and Gilday, AD and He, Z and Li, Y and Harvey, D and Larson, TR and Graham, IA}, title = {MOTHER-OF-FT-AND-TFL1 represses seed germination under far-red light by modulating phytohormone responses in Arabidopsis thaliana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8442-8447}, pmid = {30061395}, issn = {1091-6490}, support = {BB/J00216X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Abscisic Acid/physiology ; Arabidopsis/*physiology ; Arabidopsis Proteins/genetics/*physiology ; Basic Helix-Loop-Helix Transcription Factors/physiology ; Basic-Leucine Zipper Transcription Factors/genetics/physiology ; Carrier Proteins/genetics/*physiology ; Germination/*physiology ; Gibberellins/physiology ; Light ; Plant Growth Regulators/*physiology ; Signal Transduction/physiology ; }, abstract = {Seed germination in many plant species is triggered by sunlight, which is rich in the red (R) wavelength and repressed by under-the-canopy light rich in far red (FR). R:FR ratios are sensed by phytochromes to regulate levels of gibberellins (GAs) and abscisic acid (ABA), which induce and inhibit germination respectively. In this study we have discovered that, under FR light conditions, germination is repressed by MOTHER-OF-FT-AND-TFL1 (MFT) through the regulation of the ABA and GA signaling pathways. We also show that MFT gene expression is tightly regulated by light quality. Previous work has shown that under FR light conditions the transcription factor PHYOCHROME-INTERACTING-FACTOR1 (PIF1) accumulates and promotes expression of SOMNUS (SOM) that, in turn, leads to increased ABA and decreased GA levels. PIF1 also promotes expression of genes encoding ABA-INSENSITIVE5 (ABI5) and DELLA growth-repressor proteins, which act in the ABA and GA signaling pathways, respectively. Here we show that MFT gene expression is promoted by FR light through the PIF1/SOM/ABI5/DELLA pathway and is repressed by R light via the transcription factor SPATULA (SPT). Consistent with this, we also show that SPT gene expression is repressed under FR light in a PIF1-dependent manner. Furthermore, transcriptomic analyses presented in this study indicate that MFT exerts its function by promoting expression of known ABA-induced genes and repressing cell wall expansion-related genes.}, } @article {pmid30061394, year = {2018}, author = {Madhivanan, K and Greiner, ER and Alves-Ferreira, M and Soriano-Castell, D and Rouzbeh, N and Aguirre, CA and Paulsson, JF and Chapman, J and Jiang, X and Ooi, FK and Lemos, C and Dillin, A and Prahlad, V and Kelly, JW and Encalada, SE}, title = {Cellular clearance of circulating transthyretin decreases cell-nonautonomous proteotoxicity in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7710-E7719}, pmid = {30061394}, issn = {1091-6490}, support = {R01 AG050653/AG/NIA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 DK046335/DK/NIDDK NIH HHS/United States ; R37 DK046335/DK/NIDDK NIH HHS/United States ; R01 AG038664/AG/NIA NIH HHS/United States ; R01 AG049483/AG/NIA NIH HHS/United States ; }, mesh = {Amyloid Neuropathies/genetics/metabolism ; Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/cytology/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Humans ; Prealbumin/genetics/*metabolism ; *Protein Aggregates ; Protein Aggregation, Pathological/genetics/metabolism ; }, abstract = {Cell-autonomous and cell-nonautonomous mechanisms of neurodegeneration appear to occur in the proteinopathies, including Alzheimer's and Parkinson's diseases. However, how neuronal toxicity is generated from misfolding-prone proteins secreted by nonneuronal tissues and whether modulating protein aggregate levels at distal locales affects the degeneration of postmitotic neurons remains unknown. We generated and characterized animal models of the transthyretin (TTR) amyloidoses that faithfully recapitulate cell-nonautonomous neuronal proteotoxicity by expressing human TTR in the Caenorhabditis elegans muscle. We identified sensory neurons with affected morphological and behavioral nociception-sensing impairments. Nonnative TTR oligomer load and neurotoxicity increased following inhibition of TTR degradation in distal macrophage-like nonaffected cells. Moreover, reducing TTR levels by RNAi or by kinetically stabilizing natively folded TTR pharmacologically decreased TTR aggregate load and attenuated neuronal dysfunction. These findings reveal a critical role for in trans modulation of aggregation-prone degradation that directly affects postmitotic tissue degeneration observed in the proteinopathies.}, } @article {pmid30061393, year = {2018}, author = {Zaferani, M and Cheong, SH and Abbaspourrad, A}, title = {Rheotaxis-based separation of sperm with progressive motility using a microfluidic corral system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8272-8277}, pmid = {30061393}, issn = {1091-6490}, mesh = {Animals ; Cattle ; Cell Separation/*methods ; Humans ; *Lab-On-A-Chip Devices ; Male ; *Sperm Motility ; }, abstract = {The separation of motile sperm from semen samples is sought after for medical infertility treatments. In this work, we demonstrate a high-throughput microfluidic device that can passively isolate motile sperm within corrals inside a fluid channel, separating them from the rest of the diluted sample. Using finite element method simulations and proposing a model for sperm motion, we investigated how flow rate can provide a rheotaxis zone in front of the corral for sperm to move upstream/downstream depending on their motility. Using three different flow rates that provided shear rates above the minimum value within the rheotaxis zone, we experimentally tested the device with human and bovine semen. By taking advantage of the rheotactic behavior of sperm, this microfluidic device is able to corral motile sperm with progressive velocities in the range of 48-93 μm⋅s-1 and 51-82 μm⋅s-1 for bovine and human samples, respectively. More importantly, we demonstrate that the separated fractions of both human and bovine samples feature 100% normal progressive motility. Furthermore, by extracting the sperm swimming distribution within the rheotaxis zone and sperm velocity distribution inside the corral, we show that the minimum velocity of the corralled sperm can be adjusted by changing the flow rate; that is, we are able to control the motility of the separated sample. This microfluidic device is simple to use, is robust, and has a high throughput compared with traditional methods of motile sperm separation, fulfilling the needs for sperm sample preparation for medical treatments, clinical applications, and fundamental studies.}, } @article {pmid30061392, year = {2018}, author = {Yu, J and Knoppová, J and Michoux, F and Bialek, W and Cota, E and Shukla, MK and Strašková, A and Pascual Aznar, G and Sobotka, R and Komenda, J and Murray, JW and Nixon, PJ}, title = {Ycf48 involved in the biogenesis of the oxygen-evolving photosystem II complex is a seven-bladed beta-propeller protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7824-E7833}, pmid = {30061392}, issn = {1091-6490}, support = {BB/F023308/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I00937X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L003260/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Cyanobacteria/genetics/*metabolism ; Photosystem I Protein Complex/biosynthesis/genetics ; Photosystem II Protein Complex/*biosynthesis/genetics ; }, abstract = {Robust photosynthesis in chloroplasts and cyanobacteria requires the participation of accessory proteins to facilitate the assembly and maintenance of the photosynthetic apparatus located within the thylakoid membranes. The highly conserved Ycf48 protein acts early in the biogenesis of the oxygen-evolving photosystem II (PSII) complex by binding to newly synthesized precursor D1 subunit and by promoting efficient association with the D2 protein to form a PSII reaction center (PSII RC) assembly intermediate. Ycf48 is also required for efficient replacement of damaged D1 during the repair of PSII. However, the structural features underpinning Ycf48 function remain unclear. Here we show that Ycf48 proteins encoded by the thermophilic cyanobacterium Thermosynechococcus elongatus and the red alga Cyanidioschyzon merolae form seven-bladed beta-propellers with the 19-aa insertion characteristic of eukaryotic Ycf48 located at the junction of blades 3 and 4. Knowledge of these structures has allowed us to identify a conserved "Arg patch" on the surface of Ycf48 that is important for binding of Ycf48 to PSII RCs but also to larger complexes, including trimeric photosystem I (PSI). Reduced accumulation of chlorophyll in the absence of Ycf48 and the association of Ycf48 with PSI provide evidence of a more wide-ranging role for Ycf48 in the biogenesis of the photosynthetic apparatus than previously thought. Copurification of Ycf48 with the cyanobacterial YidC protein insertase supports the involvement of Ycf48 during the cotranslational insertion of chlorophyll-binding apopolypeptides into the membrane.}, } @article {pmid30061391, year = {2018}, author = {Kc, S and Wurzer, M and Speringer, M and Lutz, W}, title = {Future population and human capital in heterogeneous India.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8328-8333}, pmid = {30061391}, issn = {1091-6490}, mesh = {Educational Status ; Family Planning Services ; Female ; Fertility ; Humans ; India ; Male ; *Population Growth ; }, abstract = {Within the next decade India is expected to surpass China as the world's most populous country due to still higher fertility and a younger population. Around 2025 each country will be home to around 1.5 billion people. India is demographically very heterogeneous with some rural illiterate populations still having more than four children on average while educated urban women have fewer than 1.5 children and with great differences between states. We show that the population outlook greatly depends on the degree to which this heterogeneity is explicitly incorporated into the population projection model used. The conventional projection model, considering only the age and sex structures of the population at the national level, results in a lower projected population than the same model applied at the level of states because over time the high-fertility states gain more weight, thus applying the higher rates to more people. The opposite outcome results from an explicit consideration of education differentials because over time the proportion of more educated women with lower fertility increases, thus leading to lower predicted growth than in the conventional model. To comprehensively address this issue, we develop a five-dimensional model of India's population by state, rural/urban place of residence, age, sex, and level of education and show the impacts of different degrees of aggregation. We also provide human capital scenarios for all Indian states that suggest that India will rapidly catch up with other more developed countries in Asia if the recent pace of education expansion is maintained.}, } @article {pmid30061390, year = {2018}, author = {Honda, A and Kita, T and Seshadri, SV and Misaki, K and Ahmed, Z and Ladbury, JE and Richardson, GP and Yonemura, S and Ladher, RK}, title = {FGFR1-mediated protocadherin-15 loading mediates cargo specificity during intraflagellar transport in inner ear hair-cell kinocilia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8388-8393}, pmid = {30061390}, issn = {1091-6490}, mesh = {Adaptor Proteins, Vesicular Transport/physiology ; Animals ; Cadherins/*physiology ; Chick Embryo ; Clathrin/physiology ; Flagella/*metabolism ; Hair Cells, Auditory, Inner/*metabolism ; Mice ; Phosphorylation ; Protein Precursors/*physiology ; Protein Transport ; Receptor, Fibroblast Growth Factor, Type 1/analysis/*physiology ; }, abstract = {The mechanosensory hair cells of the inner ear are required for hearing and balance and have a distinctive apical structure, the hair bundle, that converts mechanical stimuli into electrical signals. This structure comprises a single cilium, the kinocilium, lying adjacent to an ensemble of actin-based projections known as stereocilia. Hair bundle polarity depends on kinociliary protocadherin-15 (Pcdh15) localization. Protocadherin-15 is found only in hair-cell kinocilia, and is not localized to the primary cilia of adjacent supporting cells. Thus, Pcdh15 must be specifically targeted and trafficked into the hair-cell kinocilium. Here we show that kinocilial Pcdh15 trafficking relies on cell type-specific coupling to the generic intraflagellar transport (IFT) transport mechanism. We uncover a role for fibroblast growth factor receptor 1 (FGFR1) in loading Pcdh15 onto kinociliary transport particles in hair cells. We find that on activation, FGFR1 binds and phosphorylates Pcdh15. Moreover, we find a previously uncharacterized role for clathrin in coupling this kinocilia-specific cargo with the anterograde IFT-B complex through the adaptor, DAB2. Our results identify a modified ciliary transport pathway used for Pcdh15 transport into the cilium of the inner ear hair cell and coordinated by FGFR1 activity.}, } @article {pmid30061389, year = {2018}, author = {Yang, J and Xie, X and Xiang, N and Tian, ZX and Dixon, R and Wang, YP}, title = {Polyprotein strategy for stoichiometric assembly of nitrogen fixation components for synthetic biology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8509-E8517}, pmid = {30061389}, issn = {1091-6490}, support = {BBS/E/J/000PR9797//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Bacterial Proteins/biosynthesis/genetics ; Endopeptidases/genetics/metabolism ; *Escherichia coli/genetics/metabolism ; Klebsiella oxytoca/*genetics ; *Microorganisms, Genetically-Modified/genetics/metabolism ; *Nitrogen Fixation ; *Operon ; *Polyproteins/biosynthesis/genetics ; }, abstract = {Re-engineering of complex biological systems (CBS) is an important goal for applications in synthetic biology. Efforts have been made to simplify CBS by refactoring a large number of genes with rearranged polycistrons and synthetic regulatory circuits. Here, a posttranslational protein-splicing strategy derived from RNA viruses was exploited to minimize gene numbers of the classic nitrogenase system, where the expression stoichiometry is particularly important. Operon-based nif genes from Klebsiella oxytoca were regrouped into giant genes either by fusing genes together or by expressing polyproteins that are subsequently cleaved with Tobacco Etch Virus protease. After several rounds of selection based on protein expression levels and tolerance toward a remnant C-terminal ENLYFQ-tail, a system with only five giant genes showed optimal nitrogenase activity and supported diazotrophic growth of Escherichia coli This study provides an approach for efficient translation from an operon-based system into a polyprotein-based assembly that has the potential for portable and stoichiometric expression of the complex nitrogenase system in eukaryotic organisms.}, } @article {pmid30061388, year = {2018}, author = {Kurnik, M and Ortega, G and Dauphin-Ducharme, P and Li, H and Caceres, A and Plaxco, KW}, title = {Quantitative measurements of protein-surface interaction thermodynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8352-8357}, pmid = {30061388}, issn = {1091-6490}, support = {R01 GM118560/GM/NIGMS NIH HHS/United States ; R21 EB018617/EB/NIBIB NIH HHS/United States ; }, mesh = {Electrochemical Techniques ; Humans ; *Protein Folding ; Protein Stability ; Proto-Oncogene Proteins c-fyn/*chemistry ; *Thermodynamics ; *src Homology Domains ; }, abstract = {Whereas proteins generally remain stable upon interaction with biological surfaces, they frequently unfold on and adhere to artificial surfaces. Understanding the physicochemical origins of this discrepancy would facilitate development of protein-based sensors and other technologies that require surfaces that do not compromise protein structure and function. To date, however, only a small number of such artificial surfaces have been reported, and the physics of why these surfaces support functional biomolecules while others do not has not been established. Thus motivated, we have developed an electrochemical approach to determining the folding free energy of proteins site-specifically attached to chemically well-defined, macroscopic surfaces. Comparison with the folding free energies seen in bulk solution then provides a quantitative measure of the extent to which surface interactions alter protein stability. As proof-of-principle, we have characterized the FynSH3 domain site-specifically attached to a hydroxyl-coated surface. Upon guanidinium chloride denaturation, the protein unfolds in a reversible, two-state manner with a free energy within 2 kJ/mol of the value seen in bulk solution. Assuming that excluded volume effects stabilize surface-attached proteins, this observation suggests there are countervening destabilizing interactions with the surface that, under these conditions, are similar in magnitude. Our technique constitutes an unprecedented experimental tool with which to answer long-standing questions regarding the molecular-scale origins of protein-surface interactions and to facilitate rational optimization of surface biocompatibility.}, } @article {pmid30061387, year = {2018}, author = {Hansen, AL and Buchan, GJ and Rühl, M and Mukai, K and Salvatore, SR and Ogawa, E and Andersen, SD and Iversen, MB and Thielke, AL and Gunderstofte, C and Motwani, M and Møller, CT and Jakobsen, AS and Fitzgerald, KA and Roos, J and Lin, R and Maier, TJ and Goldbach-Mansky, R and Miner, CA and Qian, W and Miner, JJ and Rigby, RE and Rehwinkel, J and Jakobsen, MR and Arai, H and Taguchi, T and Schopfer, FJ and Olagnier, D and Holm, CK}, title = {Nitro-fatty acids are formed in response to virus infection and are potent inhibitors of STING palmitoylation and signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7768-E7775}, pmid = {30061387}, issn = {1091-6490}, support = {R01 DK112854/DK/NIDDK NIH HHS/United States ; R01 GM125944/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases of the Nervous System/genetics/metabolism/pathology ; Fatty Acids/*metabolism ; Herpes Simplex/genetics/*metabolism/pathology ; Herpesvirus 2, Human/*metabolism ; Humans ; Interferon Type I/genetics/metabolism ; Lipoylation ; Lupus Erythematosus, Systemic/genetics/metabolism/pathology ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Nervous System Malformations/genetics/metabolism/pathology ; RAW 264.7 Cells ; *Signal Transduction ; }, abstract = {The adaptor molecule stimulator of IFN genes (STING) is central to production of type I IFNs in response to infection with DNA viruses and to presence of host DNA in the cytosol. Excessive release of type I IFNs through STING-dependent mechanisms has emerged as a central driver of several interferonopathies, including systemic lupus erythematosus (SLE), Aicardi-Goutières syndrome (AGS), and stimulator of IFN genes-associated vasculopathy with onset in infancy (SAVI). The involvement of STING in these diseases points to an unmet need for the development of agents that inhibit STING signaling. Here, we report that endogenously formed nitro-fatty acids can covalently modify STING by nitro-alkylation. These nitro-alkylations inhibit STING palmitoylation, STING signaling, and subsequently, the release of type I IFN in both human and murine cells. Furthermore, treatment with nitro-fatty acids was sufficient to inhibit production of type I IFN in fibroblasts derived from SAVI patients with a gain-of-function mutation in STING. In conclusion, we have identified nitro-fatty acids as endogenously formed inhibitors of STING signaling and propose for these lipids to be considered in the treatment of STING-dependent inflammatory diseases.}, } @article {pmid30061386, year = {2018}, author = {Vamvaka, E and Farré, G and Molinos-Albert, LM and Evans, A and Canela-Xandri, A and Twyman, RM and Carrillo, J and Ordóñez, RA and Shattock, RJ and O'Keefe, BR and Clotet, B and Blanco, J and Khush, GS and Christou, P and Capell, T}, title = {Unexpected synergistic HIV neutralization by a triple microbicide produced in rice endosperm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7854-E7862}, pmid = {30061386}, issn = {1091-6490}, mesh = {*Anti-HIV Agents/chemistry/metabolism ; *Antibodies, Monoclonal/biosynthesis/chemistry/genetics ; *Endosperm/chemistry/genetics/metabolism ; *HIV Antibodies/biosynthesis/chemistry/genetics ; HIV Envelope Protein gp120/*antagonists & inhibitors/chemistry/genetics/metabolism ; HIV-1/*chemistry ; *Oryza/chemistry/genetics/metabolism ; *Plants, Genetically Modified/chemistry/genetics/metabolism ; }, abstract = {The transmission of HIV can be prevented by the application of neutralizing monoclonal antibodies and lectins. Traditional recombinant protein manufacturing platforms lack sufficient capacity and are too expensive for developing countries, which suffer the greatest disease burden. Plants offer an inexpensive and scalable alternative manufacturing platform that can produce multiple components in a single plant, which is important because multiple components are required to avoid the rapid emergence of HIV-1 strains resistant to single microbicides. Furthermore, crude extracts can be used directly for prophylaxis to avoid the massive costs of downstream processing and purification. We investigated whether rice could simultaneously produce three functional HIV-neutralizing proteins (the monoclonal antibody 2G12, and the lectins griffithsin and cyanovirin-N). Preliminary in vitro tests showed that the cocktail of three proteins bound to gp120 and achieved HIV-1 neutralization. Remarkably, when we mixed the components with crude extracts of wild-type rice endosperm, we observed enhanced binding to gp120 in vitro and synergistic neutralization when all three components were present. Extracts of transgenic plants expressing all three proteins also showed enhanced in vitro binding to gp120 and synergistic HIV-1 neutralization. Fractionation of the rice extracts suggested that the enhanced gp120 binding was dependent on rice proteins, primarily the globulin fraction. Therefore, the production of HIV-1 microbicides in rice may not only reduce costs compared to traditional platforms but may also provide functional benefits in terms of microbicidal potency.}, } @article {pmid30061385, year = {2018}, author = {Reshetnyak, AV and Mohanty, J and Tomé, F and Puleo, DE and Plotnikov, AN and Ahmed, M and Kaur, N and Poliakov, A and Cinnaiyan, AM and Lax, I and Schlessinger, J}, title = {Identification of a biologically active fragment of ALK and LTK-Ligand 2 (augmentor-α).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8340-8345}, pmid = {30061385}, issn = {1091-6490}, support = {S10 OD018007/OD/NIH HHS/United States ; S10 RR023748/RR/NCRR NIH HHS/United States ; T32 GM007324/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Anaplastic Lymphoma Kinase ; Animals ; Cytokines/chemistry/*isolation & purification/physiology ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; PC12 Cells ; Protein Multimerization ; Rats ; Receptor Protein-Tyrosine Kinases/chemistry/*isolation & purification/metabolism ; }, abstract = {Elucidating the physiological roles and modes of action of the recently discovered ligands (designated ALKAL1,2 or AUG-α,β) of the receptor tyrosine kinases Anaplastic Lymphoma Kinase (ALK) and Leukocyte Tyrosine Kinase (LTK) has been limited by difficulties in producing sufficient amounts of the two ligands and their poor stability. Here we describe procedures for expression and purification of AUG-α and a deletion mutant lacking the N-terminal variable region. Detailed biochemical characterization of AUG-α by mass spectrometry shows that the four conserved cysteines located in the augmentor domain (AD) form two intramolecular disulfide bridges while a fifth, primate-specific cysteine located in the N-terminal variable region mediates dimerization through formation of a disulfide bridge between two AUG-α molecules. In contrast to AUG-α, the capacity of AUG-α AD to undergo dimerization is strongly compromised. However, full-length AUG-α and the AUG-α AD deletion mutant stimulate similar tyrosine phosphorylation of cells expressing either ALK or LTK. Both AUG-α and AUG-α AD also stimulate a similar profile of MAP kinase response in L6 cells and colony formation in soft agar by autocrine stimulation of NIH 3T3 cells expressing ALK. Moreover, both AUG-α and AUG-α AD stimulate neuronal differentiation of human neuroblastoma NB1 and PC12 cells in a similar dose-dependent manner. Taken together, these experiments show that deletion of the N-terminal variable region minimally affects the activity of AUG-α toward LTK or ALK stimulation in cultured cells. Reduced dimerization might be compensated by high local concentration of AUG-α AD bound to ALK at the cell membrane and by potential ligand-induced receptor-receptor interactions.}, } @article {pmid30061384, year = {2018}, author = {Yan, B and Yao, S and Kattel, S and Wu, Q and Xie, Z and Gomez, E and Liu, P and Su, D and Chen, JG}, title = {Active sites for tandem reactions of CO2 reduction and ethane dehydrogenation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8278-8283}, pmid = {30061384}, issn = {1091-6490}, abstract = {Ethylene (C2H4) is one of the most important raw materials for chemical industry. The tandem reactions of CO2-assisted dehydrogenation of ethane (C2H6) to ethylene creates an opportunity to effectively use the underutilized ethane from shale gas while mitigating anthropogenic CO2 emissions. Here we identify the most likely active sites over CeO2-supported NiFe catalysts by using combined in situ characterization with density-functional theory (DFT) calculations. The experimental and theoretical results reveal that the Ni-FeO x interfacial sites can selectively break the C-H bonds and preserve the C-C bond of C2H6 to produce ethylene, while the Ni-CeO x interfacial sites efficiently cleave all of the C-H and C-C bonds to produce synthesis gas. Controlled synthesis of the two distinct active sites enables rational enhancement of the ethylene selectivity for the CO2-assisted dehydrogenation of ethane.}, } @article {pmid30061383, year = {2018}, author = {Oldstone, MBA and Ware, BC and Horton, LE and Welch, MJ and Aiolfi, R and Zarpellon, A and Ruggeri, ZM and Sullivan, BM}, title = {Lymphocytic choriomeningitis virus Clone 13 infection causes either persistence or acute death dependent on IFN-1, cytotoxic T lymphocytes (CTLs), and host genetics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7814-E7823}, pmid = {30061383}, issn = {1091-6490}, support = {T32 AI007036/AI/NIAID NIH HHS/United States ; UL1 TR001114/TR/NCATS NIH HHS/United States ; R01 AI009484/AI/NIAID NIH HHS/United States ; R01 AI099699/AI/NIAID NIH HHS/United States ; HHSN272201400048C/AI/NIAID NIH HHS/United States ; R01 HL135294/HL/NHLBI NIH HHS/United States ; R01 HL117722/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD/genetics/metabolism ; *CD8-Positive T-Lymphocytes/metabolism/pathology ; Humans ; *Interferon Type I/genetics/metabolism ; *Lymphocytic Choriomeningitis/genetics/metabolism/pathology ; Lymphocytic choriomeningitis virus/*physiology ; Mice ; Programmed Cell Death 1 Receptor/genetics/metabolism ; Virus Replication/*genetics ; }, abstract = {Understanding of T cell exhaustion and successful therapy to restore T cell function was first described using Clone (Cl) 13 variant selected from the lymphocytic choriomeningitis virus (LCMV) Armstrong (ARM) 53b parental strain. T cell exhaustion plays a pivotal role in both persistent infections and cancers of mice and humans. C57BL/6, BALB, SWR/J, A/J, 129, C3H, and all but one collaborative cross (CC) mouse strain following Cl 13 infection have immunosuppressed T cell responses, high PD-1, and viral titers leading to persistent infection and normal life spans. In contrast, the profile of FVB/N, NZB, PL/J, SL/J, and CC NZO mice challenged with Cl 13 is a robust T cell response, high titers of virus, PD-1, and Lag3 markers on T cells. These mice all die 7 to 9 d after Cl 13 infection. Death is due to enhanced pulmonary endothelial vascular permeability, pulmonary edema, collapse of alveolar air spaces, and respiratory failure. Pathogenesis involves abundant levels of Cl 13 receptor alpha-dystroglycan on endothelial cells, with high viral replication in such cells leading to immunopathologic injury. Death is aborted by blockade of interferon-1 (IFN-1) signaling or deletion of CD8 T cells.}, } @article {pmid30061382, year = {2018}, author = {Das, B and Dobrowolski, C and Luttge, B and Valadkhan, S and Chomont, N and Johnston, R and Bacchetti, P and Hoh, R and Gandhi, M and Deeks, SG and Scully, E and Karn, J}, title = {Estrogen receptor-1 is a key regulator of HIV-1 latency that imparts gender-specific restrictions on the latent reservoir.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7795-E7804}, pmid = {30061382}, issn = {1091-6490}, support = {K08 AI116344/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Estrogen Receptor Modulators/*pharmacology ; Estrogen Receptor alpha/*agonists/metabolism ; Female ; HIV-1/*physiology ; Humans ; Jurkat Cells ; Male ; Receptors, Antigen, T-Cell/metabolism ; *Sex Characteristics ; T-Lymphocytes/metabolism/pathology ; Transcription, Genetic/*drug effects ; Virus Latency/*drug effects ; }, abstract = {Unbiased shRNA library screens revealed that the estrogen receptor-1 (ESR-1) is a key factor regulating HIV-1 latency. In both Jurkat T cells and a Th17 primary cell model for HIV-1 latency, selective estrogen receptor modulators (SERMs, i.e., fulvestrant, raloxifene, and tamoxifen) are weak proviral activators and sensitize cells to latency-reversing agents (LRAs) including low doses of TNF-α (an NF-κB inducer), the histone deacetylase inhibitor vorinostat (soruberoylanilide hydroxamic acid, SAHA), and IL-15. To probe the physiologic relevance of these observations, leukapheresis samples from a cohort of 12 well-matched reproductive-age women and men on fully suppressive antiretroviral therapy were evaluated by an assay measuring the production of spliced envelope (env) mRNA (the EDITS assay) by next-generation sequencing. The cells were activated by T cell receptor (TCR) stimulation, IL-15, or SAHA in the presence of either β-estradiol or an SERM. β-Estradiol potently inhibited TCR activation of HIV-1 transcription, while SERMs enhanced the activity of most LRAs. Although both sexes responded to SERMs and β-estradiol, females showed much higher levels of inhibition in response to the hormone and higher reactivity in response to ESR-1 modulators than males. Importantly, the total inducible RNA reservoir, as measured by the EDITS assay, was significantly smaller in the women than in the men. We conclude that concurrent exposure to estrogen is likely to limit the efficacy of viral emergence from latency and that ESR-1 is a pharmacologically attractive target that can be exploited in the design of therapeutic strategies for latency reversal.}, } @article {pmid30060909, year = {2018}, author = {Dussault, AC}, title = {Functional ecology's non-selectionist understanding of function.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {70}, number = {}, pages = {1-9}, doi = {10.1016/j.shpsc.2018.05.001}, pmid = {30060909}, issn = {1879-2499}, mesh = {*Biodiversity ; *Ecology ; *Ecosystem ; Philosophy ; }, abstract = {This paper reinforces the current consensus against the applicability of the selected effect theory of function in ecology. It does so by presenting an argument which, in contrast with the usual argument invoked in support of this consensus, is not based on claims about whether ecosystems are customary units of natural selection. Instead, the argument developed here is based on observations about the use of the function concept in functional ecology, and more specifically, research into the relationship between biodiversity and ecosystem functioning. It is argued that a selected effect account of ecological functions is made implausible by the fact that it would conflict with important aspects of the understanding of function and ecosystem functional organization which underpins functional ecology's research program. Specifically, it would conflict with (1) Functional ecology's adoption of a context-based understanding of function and its aim to study the functional equivalence between phylogenetically-divergent organisms; (2) Functional ecology's attribution to ecosystems of a lower degree of part-whole integration than the one found in paradigm individual organisms; and (3) Functional ecology's adoption of a physiological or metabolic perspective on ecosystems rather than an evolutionary one.}, } @article {pmid30060762, year = {2018}, author = {Bolland, MJ and Avenell, A and Gamble, GD and Buranyi, S and Grey, A}, title = {A randomised investigation of journal responses to academic and journalist enquiry about possible scientific misconduct.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {521}, pmid = {30060762}, issn = {1756-0500}, mesh = {*Editorial Policies ; Electronic Mail ; Journalism ; *Periodicals as Topic ; Random Allocation ; *Scientific Misconduct ; }, abstract = {OBJECTIVE: We investigated whether responses about possible scientific misconduct from journals to journalists would differ in speed, usefulness, and tone from responses to academics. Twelve journals that published 23 clinical trials about which concerns had been previously raised were randomly assigned to enquiries by a journalist or academics. Emails were sent every 3 weeks to the journal editor. We recorded the time for the journal to respond, and two investigators independently assessed the usefulness and tone of the journal responses.

RESULTS: 10/12 journals responded: 3 after one email, 5 after two emails, and 2 after three emails (median time from first email to response: 21 days; no difference in response times to journalist or academics, P = 0.25). Of the 10 responses, 8 indicated the journal was investigating, 5 had a positive tone, 4 a neutral tone, and 1 a negative tone. Five of the enquiries by the academics produced information of limited use and 1 no useful information, whereas none of the 6 journalist enquiries produced useful information (P = 0.015). None of the 10 responses was considered very useful. In conclusion, journal responses to a journalist were less useful than those to academics in understanding the status or outcomes of journal investigations.}, } @article {pmid30060733, year = {2018}, author = {Zhang, JD and Hatje, K and Sturm, G and Broger, C and Ebeling, M and Burtin, M and Terzi, F and Pomposiello, SI and Badi, L}, title = {Correction to: Detect tissue heterogeneity in gene expression data with BioQC.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {558}, pmid = {30060733}, issn = {1471-2164}, abstract = {After the publication of this work [1], a mistake was noticed in the Eq. 1. Given an m × n expression matrix with m genes and samples of n tissues, the correct definition of the Gini index for gene i is.}, } @article {pmid30060732, year = {2018}, author = {Schurink, A and da Silva, VH and Velie, BD and Dibbits, BW and Crooijmans, RPMA and Franҫois, L and Janssens, S and Stinckens, A and Blott, S and Buys, N and Lindgren, G and Ducro, BJ}, title = {Copy number variations in Friesian horses and genetic risk factors for insect bite hypersensitivity.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {49}, pmid = {30060732}, issn = {1471-2156}, support = {606142//FP7 Research for the Benefit of SMEs/ ; }, abstract = {BACKGROUND: Many common and relevant diseases affecting equine welfare have yet to be tested regarding structural variants such as copy number variations (CNVs). CNVs make up a substantial proportion of total genetic variability in populations of many species, resulting in more sequence differences between individuals than SNPs. Associations between CNVs and disease phenotypes have been established in several species, but equine CNV studies have been limited. Aim of this study was to identify CNVs and to perform a genome-wide association (GWA) study in Friesian horses to identify genomic loci associated with insect bite hypersensitivity (IBH), a common seasonal allergic dermatitis observed in many horse breeds worldwide.

RESULTS: Genotypes were obtained using the Axiom® Equine Genotyping Array containing 670,796 SNPs. After quality control of genotypes, 15,041 CNVs and 5350 CNV regions (CNVRs) were identified in 222 Friesian horses. Coverage of the total genome by CNVRs was 11.2% with 49.2% of CNVRs containing genes. 58.0% of CNVRs were novel (i.e. so far only identified in Friesian horses). A SNP- and CNV-based GWA analysis was performed, where about half of the horses were affected by IBH. The SNP-based analysis showed a highly significant association between the MHC region on ECA20 and IBH in Friesian horses. Associations between the MHC region on ECA20 and IBH were also detected based on the CNV-based analysis. However, CNVs associated with IBH in Friesian horses were not often in close proximity to SNPs identified to be associated with IBH.

CONCLUSIONS: CNVs were identified in a large sample of the Friesian horse population, thereby contributing to our knowledge on CNVs in horses and facilitating our understanding of the equine genome and its phenotypic expression. A clear association was identified between the MHC region on ECA20 and IBH in Friesian horses based on both SNP- and CNV-based GWA studies. These results imply that MHC contributes to IBH sensitivity in Friesian horses. Although subsequent analyses are needed for verification, nucleotide differences, as well as more complex structural variations like CNVs, seem to contribute to IBH sensitivity. IBH should be considered as a common disease with a complex genomic architecture.}, } @article {pmid30060731, year = {2018}, author = {Gu, L and Wei, H and Wang, H and Su, J and Yu, S}, title = {Characterization and functional analysis of GhWRKY42, a group IId WRKY gene, in upland cotton (Gossypium hirsutum L.).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {48}, pmid = {30060731}, issn = {1471-2156}, support = {2016YED0101006//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: WRKY transcription factors (TFs) participate in various physiological processes of plants. Although WRKY genes have been well studied in model plants, knowledge of the functional roles of these genes is still extremely limited in cotton.

RESULTS: In this study, a group IId WRKY gene from cotton, GhWRKY42, was isolated and characterized. Our data showed that GhWRKY42 localized to the nucleus. A transactivation assay in yeast demonstrated that GhWRKY42 was not a transcriptional activator. A β-glucuronidase (GUS) activity assay revealed that the promoter of GhWRKY42 showed fragment deletion activity in Nicotiana tabacum and was mainly expressed in the roots, stems and leaves of ProGhWRKY42::GUS transgenic Arabidopsis plants. Quantitative real-time PCR (qRT-PCR) analysis indicated that GhWRKY42 was up-regulated during leaf senescence and was induced after exposure to abiotic stresses. Constitutive expression of GhWRKY42 in Arabidopsis led to a premature aging phenotype, which was correlated with an increased number of senescent leaves, reduced chlorophyll content and elevated expression of senescence-associated genes (SAGs). In addition, virus-induced gene silencing (VIGS) was used to silence the endogenous GhWRKY42 gene in cotton, and this silencing reduced plant height.

CONCLUSIONS: Our findings indicate that GhWRKY42 is involved in abiotic stress responses, premature leaf senescence and stem development. This work establishes a solid foundation for further functional analysis of the GhWRKY42 gene in cotton.}, } @article {pmid30060201, year = {2018}, author = {Moyers, BA and Zhang, J}, title = {Toward Reducing Phylostratigraphic Errors and Biases.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2037-2048}, pmid = {30060201}, issn = {1759-6653}, support = {R01 GM120093/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; *Bias ; Computer Simulation ; *Evolution, Molecular ; Humans ; Machine Learning ; Models, Genetic ; *Phylogeny ; Software ; Statistics, Nonparametric ; }, abstract = {Phylostratigraphy is a method for estimating gene age, usually applied to large numbers of genes in order to detect nonrandom age-distributions of gene properties that could shed light on mechanisms of gene origination and evolution. However, phylostratigraphy underestimates gene age with a nonnegligible probability. The underestimation is severer for genes with certain properties, creating spurious age distributions of these properties and those correlated with these properties. Here we explore three strategies to reduce phylostratigraphic error/bias. First, we test several alternative homology detection methods (PSIBLAST, HMMER, PHMMER, OMA, and GLAM2Scan) in phylostratigraphy, but fail to find any that noticeably outperforms the commonly used BLASTP. Second, using machine learning, we look for predictors of error-prone genes to exclude from phylostratigraphy, but cannot identify reliable predictors. Finally, we remove from phylostratigraphic analysis genes exhibiting errors in simulation, which by definition minimizes error/bias if the simulation is sufficiently realistic. Using this last approach, we show that some previously reported phylostratigraphic trends (e.g., younger proteins tend to evolve more rapidly and be shorter) disappear or even reverse, reconfirming the necessity of controlling phylostratigraphic error/bias. Taken together, our analyses demonstrate that phylostratigraphic errors/biases are refractory to several potential solutions but can be controlled at least partially by the exclusion of error-prone genes identified via realistic simulations. These results are expected to stimulate the judicious use of error-aware phylostratigraphy and reevaluation of previous phylostratigraphic findings.}, } @article {pmid30060195, year = {2018}, author = {Elis, S and Desmarchais, A and Cardona, E and Fouchecourt, S and Dalbies-Tran, R and Nguyen, T and Thermes, V and Maillard, V and Papillier, P and Uzbekova, S and Bobe, J and Couderc, JL and Monget, P}, title = {Genes Involved in Drosophila melanogaster Ovarian Function Are Highly Conserved Throughout Evolution.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2629-2642}, pmid = {30060195}, issn = {1759-6653}, abstract = {This work presents a systematic approach to study the conservation of genes between fruit flies and mammals. We have listed 971 Drosophila genes involved in female reproduction at the ovarian level and systematically looked for orthologs in the Ciona, zebrafish, coelacanth, lizard, chicken, and mouse. Depending on the species, the percentage of these Drosophila genes with at least one ortholog varies between 69% and 78%. In comparison, only 42% of all the Drosophila genes have an ortholog in the mouse genome (P < 0.0001), suggesting a dramatically higher evolutionary conservation of ovarian genes. The 177 Drosophila genes that have no ortholog in mice and other vertebrates correspond to genes that are involved in mechanisms of oogenesis that are specific to the fruit fly or the insects. Among 759 genes with at least one ortholog in the zebrafish, 73 have an expression enriched in the ovary in this species (RNA-seq data). Among 760 genes that have at least one ortholog in the mouse; 76 and 11 orthologs are reported to be preferentially and exclusively expressed in the mouse ovary, respectively (based on the UniGene expressed sequence tag database). Several of them are already known to play a key role in murine oogenesis and/or to be enriched in the mouse/zebrafish oocyte, whereas others have remained unreported. We have investigated, by RNA-seq and real-time quantitative PCR, the exclusive ovarian expression of 10 genes in fish and mammals. Overall, we have found several novel candidates potentially involved in mammalian oogenesis by an evolutionary approach and using the fruit fly as an animal model.}, } @article {pmid30060193, year = {2018}, author = {Stief, P and Lundgaard, ASB and Treusch, AH and Thamdrup, B and Grossart, HP and Glud, RN}, title = {Freshwater copepod carcasses as pelagic microsites of dissimilatory nitrate reduction to ammonium.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, pmid = {30060193}, issn = {1574-6941}, abstract = {A considerable fraction of freshwater zooplankton was recently found to consist of dead specimens that sink to the lake bottom. Such carcasses host intense microbial activities that may promote oxygen depletion at the microscale. Therefore, we tested the hypothesis that sinking zooplankton carcasses are microsites of anaerobic nitrogen cycling that contribute to pelagic fixed-nitrogen loss even in the presence of ambient oxygen. Incubation experiments were performed with the ubiquitous copepods Eudiaptomus sp. and Megacyclops gigas at different ambient oxygen levels that sinking carcasses encounter during their descent in stratified lakes. 15N-stable-isotope incubations revealed intense carcass-associated anaerobic nitrogen cycling only at low ambient oxygen levels (<25% air saturation). Dissimilatory nitrate reduction to ammonium (DNRA) dominated over denitrification and thus the potential for fixed-nitrogen loss was low. Consistent with this partitioning of anaerobic nitrogen cycling, the relative abundance of the carcass-associated marker gene for DNRA (nrfA) was ∼20-400 times higher than that for denitrification (nirS). Additionally, the relative nrfA and nirS abundances were ∼90-180 times higher on copepod carcasses than in lake water. This functional distinctiveness of carcass-associated bacterial communities was further substantiated by 16S rDNA-based fingerprinting. We conclude that the unique bacterial communities and microenvironments provided by zooplankton carcasses influence pelagic nitrogen cycling in lakes, but mainly at seasonally low ambient O2 levels in the bottom water.}, } @article {pmid30060190, year = {2018}, author = {Kvist, J and Gonçalves Athanàsio, C and Shams Solari, O and Brown, JB and Colbourne, JK and Pfrender, ME and Mirbahai, L}, title = {Pattern of DNA Methylation in Daphnia: Evolutionary Perspective.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1988-2007}, pmid = {30060190}, issn = {1759-6653}, support = {//Wellcome Trust/United Kingdom ; R00 HG006698/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; CpG Islands/genetics ; DNA Methylation/*genetics ; Daphnia/*genetics ; *Evolution, Molecular ; Gene Expression Regulation ; Genetic Variation ; Genotype ; Phylogeny ; Species Specificity ; }, abstract = {DNA methylation is an evolutionary ancient epigenetic modification that is phylogenetically widespread. Comparative studies of the methylome across a diverse range of non-conventional and conventional model organisms is expected to help reveal how the landscape of DNA methylation and its functions have evolved. Here, we explore the DNA methylation profile of two species of the crustacean Daphnia using whole genome bisulfite sequencing. We then compare our data with the methylomes of two insects and two mammals to achieve a better understanding of the function of DNA methylation in Daphnia. Using RNA-sequencing data for all six species, we investigate the correlation between DNA methylation and gene expression. DNA methylation in Daphnia is mainly enriched within the coding regions of genes, with the highest methylation levels observed at exons 2-4. In contrast, vertebrate genomes are globally methylated, and increase towards the highest methylation levels observed at exon 2, and maintained across the rest of the gene body. Although DNA methylation patterns differ among all species, their methylation profiles share a bimodal distribution across the genomes. Genes with low levels of CpG methylation and gene expression are mainly enriched for species specific genes. In contrast, genes associated with high methylated CpG sites are highly transcribed and evolutionary conserved across all species. Finally, the positive correlation between internal exons and gene expression potentially points to an evolutionary conserved mechanism, whereas the negative regulation of gene expression via methylation of promoters and exon 1 is potentially a secondary mechanism that has been evolved in vertebrates.}, } @article {pmid30060189, year = {2018}, author = {Río Bártulos, C and Rogers, MB and Williams, TA and Gentekaki, E and Brinkmann, H and Cerff, R and Liaud, MF and Hehl, AB and Yarlett, NR and Gruber, A and Kroth, PG and van der Giezen, M}, title = {Mitochondrial Glycolysis in a Major Lineage of Eukaryotes.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2310-2325}, pmid = {30060189}, issn = {1759-6653}, support = {//Wellcome Trust/United Kingdom ; 078566/A/05/Z//Wellcome Trust/United Kingdom ; }, abstract = {The establishment of the mitochondrion is seen as a transformational step in the origin of eukaryotes. With the mitochondrion came bioenergetic freedom to explore novel evolutionary space leading to the eukaryotic radiation known today. The tight integration of the bacterial endosymbiont with its archaeal host was accompanied by a massive endosymbiotic gene transfer resulting in a small mitochondrial genome which is just a ghost of the original incoming bacterial genome. This endosymbiotic gene transfer resulted in the loss of many genes, both from the bacterial symbiont as well the archaeal host. Loss of genes encoding redundant functions resulted in a replacement of the bulk of the host's metabolism for those originating from the endosymbiont. Glycolysis is one such metabolic pathway in which the original archaeal enzymes have been replaced by bacterial enzymes from the endosymbiont. Glycolysis is a major catabolic pathway that provides cellular energy from the breakdown of glucose. The glycolytic pathway of eukaryotes appears to be bacterial in origin, and in well-studied model eukaryotes it takes place in the cytosol. In contrast, here we demonstrate that the latter stages of glycolysis take place in the mitochondria of stramenopiles, a diverse and ecologically important lineage of eukaryotes. Although our work is based on a limited sample of stramenopiles, it leaves open the possibility that the mitochondrial targeting of glycolytic enzymes in stramenopiles might represent the ancestral state for eukaryotes.}, } @article {pmid30060184, year = {2018}, author = {Narrowe, AB and Spang, A and Stairs, CW and Caceres, EF and Baker, BJ and Miller, CS and Ettema, TJG}, title = {Complex Evolutionary History of Translation Elongation Factor 2 and Diphthamide Biosynthesis in Archaea and Parabasalids.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2380-2393}, pmid = {30060184}, issn = {1759-6653}, support = {310039//European Research Council/International ; }, abstract = {Diphthamide is a modified histidine residue which is uniquely present in archaeal and eukaryotic elongation factor 2 (EF-2), an essential GTPase responsible for catalyzing the coordinated translocation of tRNA and mRNA through the ribosome. In part due to the role of diphthamide in maintaining translational fidelity, it was previously assumed that diphthamide biosynthesis genes (dph) are conserved across all eukaryotes and archaea. Here, comparative analysis of new and existing genomes reveals that some archaea (i.e., members of the Asgard superphylum, Geoarchaea, and Korarchaeota) and eukaryotes (i.e., parabasalids) lack dph. In addition, while EF-2 was thought to exist as a single copy in archaea, many of these dph-lacking archaeal genomes encode a second EF-2 paralog missing key residues required for diphthamide modification and for normal translocase function, perhaps suggesting functional divergence linked to loss of diphthamide biosynthesis. Interestingly, some Heimdallarchaeota previously suggested to be most closely related to the eukaryotic ancestor maintain dph genes and a single gene encoding canonical EF-2. Our findings reveal that the ability to produce diphthamide, once thought to be a universal feature in archaea and eukaryotes, has been lost multiple times during evolution, and suggest that anticipated compensatory mechanisms evolved independently.}, } @article {pmid30060177, year = {2018}, author = {Wei, W and Xiong, L and Ye, YN and Du, MZ and Gao, YZ and Zhang, KY and Jin, YT and Yang, Z and Wong, PC and Lau, SKP and Kan, B and Zhu, J and Woo, PCY and Guo, FB}, title = {Mutation Landscape of Base Substitutions, Duplications, and Deletions in the Representative Current Cholera Pandemic Strain.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2072-2085}, pmid = {30060177}, issn = {1759-6653}, mesh = {Base Pairing/*genetics ; Cholera/*epidemiology/*microbiology ; Chromosomes, Bacterial/genetics ; Culture Media ; DNA Replication Timing/drug effects ; *Gene Deletion ; *Gene Duplication ; Genomic Islands ; Humans ; Mutation Rate ; *Pandemics ; Reproducibility of Results ; Rifampin/pharmacology ; Vibrio cholerae/drug effects/*genetics ; }, abstract = {Pandemic cholera is a major concern for public health because of its high mortality and morbidity. Mutation accumulation (MA) experiments were performed on a representative strain of the current cholera pandemic. Although the base-pair substitution mutation rates in Vibrio cholerae (1.24 × 10-10 per site per generation for wild-type lines and 3.29 × 10-8 for mismatch repair deficient lines) are lower than that previously reported in other bacteria using MA analysis, we discovered specific high rates (8.31 × 10-8 site/generation for wild-type lines and 1.82 × 10-6 for mismatch repair deficient lines) of base duplication or deletion driven by large-scale copy number variations (CNVs). These duplication-deletions are located in two pathogenic islands, IMEX and the large integron island. Each element of these islands has discrepant rate in rapid integration and excision, which provides clues to the pandemicity evolution of V. cholerae. These results also suggest that large-scale structural variants such as CNVs can accumulate rapidly during short-term evolution. Mismatch repair deficient lines exhibit a significantly increased mutation rate in the larger chromosome (Chr1) at specific regions, and this pattern is not observed in wild-type lines. We propose that the high frequency of GATC sites in Chr1 improves the efficiency of MMR, resulting in similar rates of mutation in the wild-type condition. In addition, different mutation rates and spectra were observed in the MA lines under distinct growth conditions, including minimal media, rich media and antibiotic treatments.}, } @article {pmid30060169, year = {2018}, author = {Allué-Guardia, A and Koenig, SSK and Quirós, P and Muniesa, M and Bono, JL and Eppinger, M}, title = {Closed Genome and Comparative Phylogenetic Analysis of the Clinical Multidrug Resistant Shigella sonnei Strain 866.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2241-2247}, pmid = {30060169}, issn = {1759-6653}, support = {SC2 AI120941/AI/NIAID NIH HHS/United States ; }, abstract = {Shigella sonnei is responsible for the majority of shigellosis infections in the US with over 500,000 cases reported annually. Here, we present the complete genome of the clinical multidrug resistant (MDR) strain 866, which is highly susceptible to bacteriophage infections. The strain has a circular chromosome of 4.85 Mb and carries a 113 kb MDR plasmid. This IncB/O/K/Z-type plasmid, termed p866, confers resistance to five different classes of antibiotics including ß-lactamase, sulfonamide, tetracycline, aminoglycoside, and trimethoprim. Comparative analysis of the plasmid architecture and gene inventory revealed that p866 shares its plasmid backbone with previously described IncB/O/K/Z-type Shigella spp. and Escherichia coli plasmids, but is differentiated by the insertion of antibiotic resistance cassettes, which we found associated with mobile genetic elements such as Tn3, Tn7, and Tn10. A whole genome-derived phylogenetic reconstruction showed the evolutionary relationships of S. sonnei strain 866 and the four established Shigella species, highlighting the clonal nature of S. sonnei.}, } @article {pmid30060167, year = {2018}, author = {Lamelas, A and Hamid, AM and Dangy, JP and Hauser, J and Jud, M and Röltgen, K and Hodgson, A and Junghanss, T and Harris, SR and Parkhill, J and Bentley, SD and Pluschke, G}, title = {Loss of Genomic Diversity in a Neisseria meningitidis Clone Through a Colonization Bottleneck.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2102-2109}, pmid = {30060167}, issn = {1759-6653}, mesh = {Genetic Variation ; Ghana ; Humans ; Meningitis/cerebrospinal fluid/microbiology ; Neisseria meningitidis/*genetics/isolation & purification ; Phylogeny ; Recombination, Genetic ; }, abstract = {Neisseria meningitidis is the leading cause of epidemic meningitis in the "meningitis belt" of Africa, where clonal waves of colonization and disease are observed. Point mutations and horizontal gene exchange lead to constant diversification of meningococcal populations during clonal spread. Maintaining a high genomic diversity may be an evolutionary strategy of meningococci that increases chances of fixing occasionally new highly successful "fit genotypes". We have performed a longitudinal study of meningococcal carriage and disease in northern Ghana by analyzing cerebrospinal fluid samples from all suspected meningitis cases and monitoring carriage of meningococci by twice yearly colonization surveys. In the framework of this study, we observed complete replacement of an A: sequence types (ST)-2859 clone by a W: ST-2881 clone. However, after a gap of 1 year, A: ST-2859 meningococci re-emerged both as colonizer and meningitis causing agent. Our whole genome sequencing analyses compared the A population isolated prior to the W colonization and disease wave with the re-emerging A meningococci. This analysis revealed expansion of one clone differing in only one nonsynonymous SNP from several isolates already present in the original A: ST-2859 population. The colonization bottleneck caused by the competing W meningococci thus resulted in a profound reduction in genomic diversity of the A meningococcal population.}, } @article {pmid30060147, year = {2018}, author = {Abalde, S and Tenorio, MJ and Afonso, CML and Zardoya, R}, title = {Conotoxin Diversity in Chelyconus ermineus (Born, 1778) and the Convergent Origin of Piscivory in the Atlantic and Indo-Pacific Cones.}, journal = {Genome biology and evolution}, volume = {10}, number = {10}, pages = {2643-2662}, pmid = {30060147}, issn = {1759-6653}, abstract = {The transcriptome of the venom duct of the Atlantic piscivorous cone species Chelyconus ermineus (Born, 1778) was determined. The venom repertoire of this species includes at least 378 conotoxin precursors, which could be ascribed to 33 known and 22 new (unassigned) protein superfamilies, respectively. Most abundant superfamilies were T, W, O1, M, O2, and Z, accounting for 57% of all detected diversity. A total of three individuals were sequenced showing considerable intraspecific variation: each individual had many exclusive conotoxin precursors, and only 20% of all inferred mature peptides were common to all individuals. Three different regions (distal, medium, and proximal with respect to the venom bulb) of the venom duct were analyzed independently. Diversity (in terms of number of distinct members) of conotoxin precursor superfamilies increased toward the distal region whereas transcripts detected toward the proximal region showed higher expression levels. Only the superfamilies A and I3 showed statistically significant differential expression across regions of the venom duct. Sequences belonging to the alpha (motor cabal) and kappa (lightning-strike cabal) subfamilies of the superfamily A were mainly detected in the proximal region of the venom duct. The mature peptides of the alpha subfamily had the α4/4 cysteine spacing pattern, which has been shown to selectively target muscle nicotinic-acetylcholine receptors, ultimately producing paralysis. This function is performed by mature peptides having a α3/5 cysteine spacing pattern in piscivorous cone species from the Indo-Pacific region, thereby supporting a convergent evolution of piscivory in cones.}, } @article {pmid30060135, year = {2018}, author = {Melo, LDR and França, A and Brandão, A and Sillankorva, S and Cerca, N and Azeredo, J}, title = {Assessment of Sep1virus interaction with stationary cultures by transcriptional and flow cytometry studies.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy143}, pmid = {30060135}, issn = {1574-6941}, abstract = {The majority of phage infection studies are performed in bacteria that are growing exponentially, although in nature, phages usually interact also with non-replicating cells. These stationary-phase cells differ from exponential cells morphologically, physiologically and metabolically. The interaction of a Sep1virus with Staphylococcus epidermidis stationary and exponential phase cells was explored. Phage SEP1 efficiently infected both cell culture states, without the addition of any fresh nutrients to stationary cultures. Phage-host interactions, analysed by flow cytometry, showed stationary-phase cells response to phage immediately after SEP1 addition. Quantitative PCR experiments corroborate that phage genes are expressed within 5 min of contact with stationary phase cells. The increase of host RNA polymerase transcripts in stationary cells suggests that SEP1 infection leads to the upregulation of host machinery fundamental for completion of its lytic life cycle. SEP1 infection and replication process highlights its potential clinical interest targeting stationary phase cells.}, } @article {pmid30060094, year = {2018}, author = {Vetukuri, RR and Tripathy, S and Malar C, M and Panda, A and Kushwaha, SK and Chawade, A and Andreasson, E and Grenville-Briggs, LJ and Whisson, SC}, title = {Draft Genome Sequence for the Tree Pathogen Phytophthora plurivora.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2432-2442}, pmid = {30060094}, issn = {1759-6653}, abstract = {Species from the genus Phytophthora are well represented among organisms causing serious diseases on trees. Phytophthora plurivora has been implicated in long-term decline of woodland trees across Europe. Here we present a draft genome sequence of P. plurivora, originally isolated from diseased European beech (Fagus sylvatica) in Malmö, Sweden. When compared with other sequenced Phytophthora species, the P. plurivora genome assembly is relatively compact, spanning 41 Mb. This is organized in 1,919 contigs and 1,898 scaffolds, encompassing 11,741 predicted genes, and has a repeat content of approximately 15%. Comparison of allele frequencies revealed evidence for tetraploidy in the sequenced isolate. As in other sequenced Phytophthora species, P. plurivora possesses genes for pathogenicity-associated RXLR and Crinkle and Necrosis effectors, predominantly located in gene-sparse genomic regions. Comparison of the P. plurivora RXLR effectors with orthologs in other sequenced species in the same clade (Phytophthora multivora and Phytophthora capsici) revealed that the orthologs were likely to be under neutral or purifying selection.}, } @article {pmid30060072, year = {2018}, author = {Gillespie, JJ and Driscoll, TP and Verhoeve, VI and Rahman, MS and Macaluso, KR and Azad, AF}, title = {A Tangled Web: Origins of Reproductive Parasitism.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2292-2309}, pmid = {30060072}, issn = {1759-6653}, support = {R01 AI122672/AI/NIAID NIH HHS/United States ; R01 AI017828/AI/NIAID NIH HHS/United States ; R01 AI126853/AI/NIAID NIH HHS/United States ; }, abstract = {While typically a flea parasite and opportunistic human pathogen, the presence of Rickettsia felis (strain LSU-Lb) in the non-blood-feeding, parthenogenetically reproducing booklouse, Liposcelis bostrychophila, provides a system to ascertain factors governing not only host transitions but also obligate reproductive parasitism (RP). Analysis of plasmid pLbAR, unique to R. felis str. LSU-Lb, revealed a toxin-antitoxin module with similar features to prophage-encoded toxin-antitoxin modules utilized by parasitic Wolbachia strains to induce another form of RP, cytoplasmic incompatibility, in their arthropod hosts. Curiously, multiple deubiquitinase and nuclease domains of the large (3,841 aa) pLbAR toxin, as well the entire antitoxin, facilitated the detection of an assortment of related proteins from diverse intracellular bacteria, including other reproductive parasites. Our description of these remarkable components of the intracellular mobilome, including their presence in certain arthropod genomes, lends insight on the evolution of RP, while invigorating research on parasite-mediated biocontrol of arthropod-borne viral and bacterial pathogens.}, } @article {pmid30060036, year = {2018}, author = {Perry, BW and Card, DC and McGlothlin, JW and Pasquesi, GIM and Adams, RH and Schield, DR and Hales, NR and Corbin, AB and Demuth, JP and Hoffmann, FG and Vandewege, MW and Schott, RK and Bhattacharyya, N and Chang, BSW and Casewell, NR and Whiteley, G and Reyes-Velasco, J and Mackessy, SP and Gamble, T and Storey, KB and Biggar, KK and Passow, CN and Kuo, CH and McGaugh, SE and Bronikowski, AM and de Koning, APJ and Edwards, SV and Pfrender, ME and Minx, P and Brodie, ED and Brodie, ED and Warren, WC and Castoe, TA}, title = {Molecular Adaptations for Sensing and Securing Prey and Insight into Amniote Genome Diversity from the Garter Snake Genome.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2110-2129}, pmid = {30060036}, issn = {1759-6653}, mesh = {Adaptation, Physiological ; Animals ; *Evolution, Molecular ; Female ; *Genome ; *Molecular Sequence Annotation ; Photoreceptor Cells, Vertebrate ; *Predatory Behavior ; Receptors, Odorant/genetics ; Reptiles/classification/genetics ; Retinal Pigments/genetics ; Selection, Genetic ; Snakes/classification/*genetics/physiology ; Venoms/genetics ; Voltage-Gated Sodium Channels/genetics ; }, abstract = {Colubridae represents the most phenotypically diverse and speciose family of snakes, yet no well-assembled and annotated genome exists for this lineage. Here, we report and analyze the genome of the garter snake, Thamnophis sirtalis, a colubrid snake that is an important model species for research in evolutionary biology, physiology, genomics, behavior, and the evolution of toxin resistance. Using the garter snake genome, we show how snakes have evolved numerous adaptations for sensing and securing prey, and identify features of snake genome structure that provide insight into the evolution of amniote genomes. Analyses of the garter snake and other squamate reptile genomes highlight shifts in repeat element abundance and expansion within snakes, uncover evidence of genes under positive selection, and provide revised neutral substitution rate estimates for squamates. Our identification of Z and W sex chromosome-specific scaffolds provides evidence for multiple origins of sex chromosome systems in snakes and demonstrates the value of this genome for studying sex chromosome evolution. Analysis of gene duplication and loss in visual and olfactory gene families supports a dim-light ancestral condition in snakes and indicates that olfactory receptor repertoires underwent an expansion early in snake evolution. Additionally, we provide some of the first links between secreted venom proteins, the genes that encode them, and their evolutionary origins in a rear-fanged colubrid snake, together with new genomic insight into the coevolutionary arms race between garter snakes and highly toxic newt prey that led to toxin resistance in garter snakes.}, } @article {pmid30060031, year = {2018}, author = {Minias, A and Minias, P and Czubat, B and Dziadek, J}, title = {Purifying selective pressure suggests the functionality of a vitamin B12 biosynthesis pathway in a global population of Mycobacterium tuberculosis.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/gbe/evy153}, pmid = {30060031}, issn = {1759-6653}, abstract = {Mycobacterium tuberculosis is one of the deadliest and most challenging pathogens to study in current microbiological research. One of the issues that remains to be resolved is the importance of cobalamin in the metabolism of M. tuberculosis. The functionality of a vitamin B12 biosynthesis pathway in M. tuberculosis is under dispute, and the ability of this pathogen to scavenge vitamin B12 from the host is unknown. Here, we quantified the ratios of non-synonymous and synonymous nucleotide substitution rates (dN/dS) in the genes involved in vitamin B12 biosynthesis and transport and in genes encoding cobalamin-dependent enzymes in nearly four thousand strains of M. tuberculosis. We showed that purifying selection is the dominant force acting on cobalamin-related genes at the levels of individual codons, genes and groups of genes. We conclude that cobalamin-related genes may not be essential but are adaptive for M. tuberculosis in clinical settings. Furthermore, the cobalamin biosynthesis pathway is likely to be functional in this species.}, } @article {pmid30059996, year = {2018}, author = {Wei, X and Zhang, J}, title = {On the Origin of Compositional Features of Ribosomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2010-2016}, pmid = {30059996}, issn = {1759-6653}, support = {R01 GM120093/GM/NIGMS NIH HHS/United States ; }, mesh = {Catalysis ; Gene Expression Regulation ; RNA, Messenger/genetics/metabolism ; RNA, Ribosomal/genetics ; Ribosomal Proteins/chemistry/genetics/metabolism ; Ribosomes/*metabolism ; }, abstract = {Ribosomes are highly abundant in cells and comprise, besides RNAs of varying lengths, 55-80 similarly sized, short proteins. This seemingly unusual composition is thought to have resulted from selection for rapid autocatalytic ribosome production. Here, we demonstrate that ribosomal protein-splitting mutations cannot accelerate ribosome production. The autocatalytic explanation is also unnecessary, because protein lengths generally decline with expression levels. Although ribosomal proteins are shorter than expected from their expression levels, they are not outliers among members of large protein complexes in mean protein length or coefficient of variation. These observations are explainable because 1) shortening proteins lowers their synthetic cost and reduces the waste from mistranslation-induced protein dysfunction and degradation, 2) such benefits rise with expression levels, and 3) members of large complexes participate in more protein-protein interactions so are less tolerant to mistranslation. These and other considerations suggest that the compositional features of ribosomes originate from cellular energy economics.}, } @article {pmid30059981, year = {2018}, author = {Panthee, S and Hamamoto, H and Ishijima, SA and Paudel, A and Sekimizu, K}, title = {Utilization of Hybrid Assembly Approach to Determine the Genome of an Opportunistic Pathogenic Fungus, Candida albicans TIMM 1768.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2017-2022}, pmid = {30059981}, issn = {1759-6653}, mesh = {Candida albicans/*genetics/pathogenicity ; Genes, Fungal ; *Genome, Fungal ; Genomics ; High-Throughput Nucleotide Sequencing/*methods ; Microbial Sensitivity Tests ; Molecular Sequence Annotation ; Phylogeny ; }, abstract = {Candida albicans TIMM1768 is a highly virulent strain utilized as a model organism for the study of gastrointestinal and oral candidiasis. Despite being a model strain, identification of its genetic determinants of pathogenesis is hindered by the unavailability of its genome sequence. In this study, we determined the genome sequence of C. albicans TIMM1768 using reads obtained from portable MinION and benchtop Ion PGM sequencers. Genome annotation and a comparative analysis with published genomes revealed that the TIMM1768 strain was close to Candida albicans CHN1, and we identified a significant number of genes encoding for pathogenesis. The availability of the C. albicans TIMM1768 genome will facilitate comparative genomic analysis of Candida species, including studies of its virulence mechanisms and the development of treatment strategies for severe candidiasis.}, } @article {pmid30059966, year = {2018}, author = {Berto, S and Nowick, K}, title = {Species-Specific Changes in a Primate Transcription Factor Network Provide Insights into the Molecular Evolution of the Primate Prefrontal Cortex.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2023-2036}, pmid = {30059966}, issn = {1759-6653}, mesh = {Adult ; Animals ; Binding Sites ; Brain/metabolism ; Cognition ; Enhancer Elements, Genetic/genetics ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Regulatory Networks ; Humans ; Macaca mulatta/*genetics ; Pan troglodytes/*genetics ; Prefrontal Cortex/*metabolism ; Species Specificity ; Transcription Factors/*metabolism ; }, abstract = {The human prefrontal cortex (PFC) differs from that of other primates with respect to size, histology, and functional abilities. Here, we analyzed genome-wide expression data of humans, chimpanzees, and rhesus macaques to discover evolutionary changes in transcription factor (TF) networks that may underlie these phenotypic differences. We determined the co-expression networks of all TFs with species-specific expression including their potential target genes and interaction partners in the PFC of all three species. Integrating these networks allowed us inferring an ancestral network for all three species. This ancestral network as well as the networks for each species is enriched for genes involved in forebrain development, axonogenesis, and synaptic transmission. Our analysis allows us to directly compare the networks of each species to determine which links have been gained or lost during evolution. Interestingly, we detected that most links were gained on the human lineage, indicating increase TF cooperativity in humans. By comparing network changes between different tissues, we discovered that in brain tissues, but not in the other tissues, the human networks always had the highest connectivity. To pinpoint molecular changes underlying species-specific phenotypes, we analyzed the sub-networks of TFs derived only from genes with species-specific expression changes in the PFC. These sub-networks differed significantly in structure and function between the human and chimpanzee. For example, the human-specific sub-network is enriched for TFs implicated in cognitive disorders and for genes involved in synaptic plasticity and cognitive functions. Our results suggest evolutionary changes in TF networks that might have shaped morphological and functional differences between primate brains, in particular in the human PFC.}, } @article {pmid30059827, year = {2018}, author = {VanderSluis, B and Costanzo, M and Billmann, M and Ward, HN and Myers, CL and Andrews, BJ and Boone, C}, title = {Integrating genetic and protein-protein interaction networks maps a functional wiring diagram of a cell.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {170-179}, doi = {10.1016/j.mib.2018.06.004}, pmid = {30059827}, issn = {1879-0364}, support = {R01 HG005084/HG/NHGRI NIH HHS/United States ; R01 HG005853/HG/NHGRI NIH HHS/United States ; }, abstract = {Systematic experimental approaches have led to construction of comprehensive genetic and protein-protein interaction networks for the budding yeast, Saccharomyces cerevisiae. Genetic interactions capture functional relationships between genes using phenotypic readouts, while protein-protein interactions identify physical connections between gene products. These complementary, and largely non-overlapping, networks provide a global view of the functional architecture of a cell, revealing general organizing principles, many of which appear to be evolutionarily conserved. Here, we focus on insights derived from the integration of large-scale genetic and protein-protein interaction networks, highlighting principles that apply to both unicellular and more complex systems, including human cells. Network integration reveals fundamental connections involving key functional modules of eukaryotic cells, defining a core network of cellular function, which could be elaborated to explore cell-type specificity in metazoans.}, } @article {pmid30059804, year = {2018}, author = {Tripathi, A and Marotz, C and Gonzalez, A and Vázquez-Baeza, Y and Song, SJ and Bouslimani, A and McDonald, D and Zhu, Q and Sanders, JG and Smarr, L and Dorrestein, PC and Knight, R}, title = {Are microbiome studies ready for hypothesis-driven research?.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {61-69}, pmid = {30059804}, issn = {1879-0364}, support = {R01 HG004872/HG/NHGRI NIH HHS/United States ; R01 HL140976/HL/NHLBI NIH HHS/United States ; R01 MD011389/MD/NIMHD NIH HHS/United States ; }, abstract = {Hypothesis-driven research has led to many scientific advances, but hypotheses cannot be tested in isolation: rather, they require a framework of aggregated scientific knowledge to allow questions to be posed meaningfully. This framework is largely still lacking in microbiome studies, and the only way to create it is by discovery-driven, tool-driven, and standards-driven research projects. Here we illustrate these issues using several such non-hypothesis-driven projects from our own laboratories, including spatial mapping, the American Gut Project, the Earth Microbiome Project (which is an umbrella project integrating many smaller hypothesis-driven projects), and the knowledgebase-driven tools GNPS and Qiita. We argue that an investment of community resources in infrastructure tasks, and in the controls and standards that underpin them, will greatly enhance the investment in hypothesis-driven research programs.}, } @article {pmid30059742, year = {2018}, author = {Clouthier, S and Anderson, E and Kurath, G and Breyta, R}, title = {Molecular systematics of sturgeon nucleocytoplasmic large DNA viruses.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {26-37}, doi = {10.1016/j.ympev.2018.07.019}, pmid = {30059742}, issn = {1095-9513}, abstract = {Namao virus (NV) is a sturgeon nucleocytoplasmic large DNA virus (sNCLDV) that can cause a lethal disease of the integumentary system in lake sturgeon Acipenser fulvescens. As a group, the sNCLDV have not been assigned to any currently recognized taxonomic family of viruses. In this study, a data set of NV DNA sequences was generated and assembled as two non-overlapping contigs of 306,448 bp and then used to conduct a comprehensive systematics analysis using Bayesian inference of phylogeny for NV, other sNCLDV and representative members of six families of the NCLDV superfamily. The phylogeny of NV was reconstructed using protein homologues encoded by nine nucleocytoplasmic virus orthologous genes (NCVOGs): NCVOG0022 - mcp, NCVOG0038 - DNA polymerase B elongation subunit, NCVOG0076 - VV A18-type helicase, NCVOG0249 - VV A32-type ATPase, NCVOG0262 - AL2 VLTF3-like transcription factor, NCVOG0271 - RNA polymerase II subunit II, NCVOG0274 - RNA polymerase II subunit I, NCVOG0276 - ribonucleotide reductase small subunit and NCVOG1117 - mRNA capping enzyme. The accuracy of our phylogenetic method was evaluated using a combination of Bayesian statistical analysis and congruence analysis. Stable tree topologies were obtained with data sets differing in target molecule(s), sequence length and taxa. Congruent topologies were obtained in phylogenies constructed using individual protein data sets. The major capsid protein phylogeny inferred that ten representative sNCLDV form a monophyletic group comprised of four lineages within a polyphyletic Mimi-Phycodnaviridae group of taxa. Overall, the analyses revealed that Namao virus is a member of the Mimiviridae family with strong and consistent support for a clade containing NV and CroV as sister taxa.}, } @article {pmid30059669, year = {2018}, author = {Yamada, S and Tanaka, Y and Imai, KS and Saigou, M and Onuma, TA and Nishida, H}, title = {Wavy movements of epidermis monocilia drive the neurula rotation that determines left-right asymmetry in ascidian embryos.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.07.023}, pmid = {30059669}, issn = {1095-564X}, abstract = {Tadpole larvae of the ascidian, Halocynthia roretzi, show morphological left-right asymmetry in the brain structures and the orientation of tail bending within the vitelline membrane. Neurula embryos rotate along the anterior-posterior axis in a counterclockwise direction, and then this rotation stops when the left side of the embryo is oriented downwards. Contact of the left-side epidermis with the vitelline membrane promotes nodal gene expression in the left-side epidermis. This is a novel mechanism in which rotation of whole embryos provides the initial cue for breaking left-right symmetry. Here we show that epidermal monocilia, which appear at the neurula rotation stage, generate the driving force for rotation. A ciliary protein, Arl13b, fused with Venus YFP was used for live imaging of ciliary movements. Although overexpression of wild-type Arl13b fusion protein resulted in aberrant movements of the cilia and abrogation of neurula rotation, mutant Arl13b fusion protein, in which the GTPase and coiled-coil domains were removed, did not affect the normal ciliary movements and neurula rotation. Epidermis cilia moved in a wavy and serpentine way like sperm flagella but not in a rotational way or beating way with effective stroke and recovery stroke. They moved very slowly, at 1/7 Hz, consistent with the low angular velocity of neurula rotation (ca. 43°/min). The tips of most cilia pointed in the opposite direction of embryonic rotation. Similar motility was also observed in Ciona robusta embryos. When embryos were treated with a dynein inhibitor, Ciliobrevin D, both ciliary movements and neurula rotation were abrogated, showing that ciliary movements drive neurula rotation in Halocynthia. The drug also inhibited Ciona neurula rotation. Our observations suggest that the driving force of rotation is generated using the vitelline membrane as a substrate but not by making a water current around the embryo. It is of evolutionary interest that ascidians use ciliary movements to break embryonic left-right symmetry, like in many vertebrates. Meanwhile, ascidian embryos rotate as a whole, similar to embryos of non-vertebrate deuterostomes, such as echinoderm, hemichordate, and amphioxus, while swimming.}, } @article {pmid30059630, year = {2018}, author = {Etienne-Manneville, S}, title = {Cytoplasmic Intermediate Filaments in Cell Biology.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {1-28}, doi = {10.1146/annurev-cellbio-100617-062534}, pmid = {30059630}, issn = {1530-8995}, abstract = {Intermediate filaments (IFs) are one of the three major elements of the cytoskeleton. Their stability, intrinsic mechanical properties, and cell type-specific expression patterns distinguish them from actin and microtubules. By providing mechanical support, IFs protect cells from external forces and participate in cell adhesion and tissue integrity. IFs form an extensive and elaborate network that connects the cell cortex to intracellular organelles. They act as a molecular scaffold that controls intracellular organization. However, IFs have been revealed as much more than just rigid structures. Their dynamics is regulated by multiple signaling cascades and appears to contribute to signaling events in response to cell stress and to dynamic cellular functions such as mitosis, apoptosis, and migration.}, } @article {pmid30059002, year = {2018}, author = {Sakdapetsiri, C and Ngaemthao, W and Suriyachadkun, C and Duangmal, K and Kitpreechavanich, V}, title = {Actinomycetospora endophytica sp. nov., isolated from wild orchid (Podochilus microphyllus Lindl.) in Thailand.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3017-3021}, doi = {10.1099/ijsem.0.002938}, pmid = {30059002}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Orchidaceae/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel endophytic actinomycete, designated strain A-T 8314T, was isolated from a wild orchid, Podochilus microphyllus Lindl., collected from Trat Province, Thailand. The taxonomic position of strain A-T 8314T was established using a combination of genotypic and phenotypic analyses. The isolate was a Gram-positive bacterium that developed bud-like spore chains. Strain A-T 8314T grew aerobically at an optimum temperature of 20-25 °C and an optimal pH 6.0. The cell wall contained meso-diaminopimelic acid, and the whole-cell sugars were ribose, arabinose and galactose. The predominant menaquinone was MK-8 (H4). The polar lipid profile contained phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, phosphatidylmonomethylethanolamine, hydroxy-phosphatidylmonomethylethanolamine and hydroxyl phosphatidylethanolamine. The predominant cellular fatty acid was iso-C16 : 0. The DNA G+C content of the genomic DNA was 73.2±0.2 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain A-T 8314T belonged to the genus Actinomycetospora, and was most closely related to Actinomycetospora chiangmaiensis YIM 0006T (98.8 %) and Actinomycetosporacorticicola 014-5T (98.6 %). The DNA-DNA relatedness values that distinguished A-T 8314T from its closest species were below 70 %. Following an evaluation of phenotypic, chemotaxonomic and genotypic studies, it was concluded that the new isolate represents as a novel species, for which the name Actinomycetospora endophytica sp. nov is proposed. The type strain is A-T 8314T (=TBRC 5722T=NBRC 113235T).}, } @article {pmid30059001, year = {2018}, author = {Normand, P and Nouioui, I and Pujic, P and Fournier, P and Dubost, A and Schwob, G and Klenk, HP and Nguyen, A and Abrouk, D and Herrera-Belaroussi, A and Pothier, JF and Pflüger, V and Fernandez, MP}, title = {Frankia canadensis sp. nov., isolated from root nodules of Alnus incana subspecies rugosa.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3001-3011}, doi = {10.1099/ijsem.0.002939}, pmid = {30059001}, issn = {1466-5034}, mesh = {Alnus/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Frankia/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; Quebec ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain ARgP5T, an actinobacterium isolated from a root nodule present on an Alnus incana subspecies rugosa shrub growing in Quebec City, Canada, was the subject of polyphasic taxonomic studies to clarify its status within the genus Frankia. 16S rRNA gene sequence similarities and ANI values between ARgP5T and type strains of species of the genus Frankiawith validly published names were 98.8 and 82 % or less, respectively. The in silico DNA G+C content was 72.4 mol%. ARgP5T is characterised by the presence of meso-A2pm, galactose, glucose, mannose, rhamnose (trace), ribose and xylose as whole-organism hydrolysates; MK-9(H8) as predominant menaquinone; diphosphatidylglycerol, phosphatidylinositol and phosphatidylglycerol as polar lipids and iso-C16 : 0 and C17 : 1ω8c as major fatty acids. The proteomic results confirmed the distinct position of ARgP5T from its closest neighbours in Frankiacluster 1. ARgP5T was found to be infective on two alder (Alnus glutinosa and Alnusalnobetula subsp. crispa) and on one bayberry (Morella pensylvanica) species and to fix nitrogen in symbiosis and in pure culture. On the basis of phylogenetic (16S rRNA gene sequence), genomic, proteomic and phenotypic results, strain ARgP5T (=DSM 45898=CECT 9033) is considered to represent a novel species within the genus Frankia for which the name Frankia canadensis sp. nov., is proposed.}, } @article {pmid30058996, year = {2018}, author = {Dobritsa, AP and Kutumbaka, KK and Samadpour, M}, title = {Reclassification of Eubacterium combesii and discrepancies in the nomenclature of botulinum neurotoxin-producing clostridia: Challenging Opinion 69. Request for an Opinion.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3068-3075}, doi = {10.1099/ijsem.0.002942}, pmid = {30058996}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Botulinum Toxins ; Clostridium/classification ; DNA, Bacterial/genetics ; Eubacterium/*classification/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {To clarify the taxonomic position of Eubacterium combesii, the whole genome of its type strain, DSM 20696T, was sequenced. Comparison of this sequence with known sequences of other bacteria confirmed that E. combesii represented a member of the Clostridium sporogenes/Clostridium botulinum Group I clade. However, the results of phylogenetic analysis also demonstrated that the latter two species did not form the same genetic entity and that E. combesii was in the C. botulinum Group I subclade. Meanwhile, we showed that E. combesii DSM 20696T did not produce botulinum neurotoxins (BoNTs) and thus should be identified as a strain of C. sporogenes in accordance with the current nomenclature of BoNT-producing clostridia, which is based, in particular, on Opinion 69 issued by the Judicial Commission of the ICSB. However, review of the corresponding Request for an Opinion revealed that it had been based on an erroneous statement. Therefore, we request reconsideration of Opinion 69 and propose to reclassify Eubacterium combesii as a later synonym of Clostridium botulinum. The results of phylogenetic analysis of the other five groups of BoNT-producing clostridia indicated that all the groups were far distant from each other. However, the members of Groups IV-VI are classified as strains of different species, while all members of Groups I-III are designated C. botulinum. Meanwhile, similarly to Group I, Groups II and III are also polyphyletic and appear to consist of two and four species, respectively. These results demonstrate, once again, discrepancies in the nomenclature of BoNT-producing bacteria and corroborate our request for reconsideration of Opinion 69.}, } @article {pmid30058994, year = {2018}, author = {Zhu, H and Fu, B and Lu, S and Liu, H and Liu, H}, title = {Clostridium bovifaecis sp. nov., a novel acetogenic bacterium isolated from cow manure.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2956-2959}, doi = {10.1099/ijsem.0.002928}, pmid = {30058994}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Cattle/*microbiology ; Clostridium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Manure/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A strictly anaerobic, Gram-staining-positive, spore-forming rod-shaped bacterium, and designated BXXT, was isolated from cow manure. Colonies on DSMZ medium 311c agar plates were cream, circular, opaque and lustrous. Growth occurred at 20-45 °C with a pH range of 5.0-10.0 and at NaCl concentrations of up to 2 % (w/v). The optimum temperature, pH and NaCl concentration for growth were 30 °C, pH 7 and 1 % (w/v), respectively. The major cellular fatty acids were C16 : 0 (26.8 %), C14 : 0 (22.8 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (16.4 %) and C16 : 1ω9c (10.7 %). The main polar lipids of BXXT were diphosphatidylglycerol, phosphatidylethanolamine, unidentified aminolipids, an unidentified phospholipid and unidentified lipids. Acetate was mainly produced from H2/CO2, H2/CO2/CO (4/3/3, v/v/v), formate, glycerol, 1,2-propanediol, pyruvate, d-fructose and 2-methoxyethanol. BXXT is most closely related to Clostridium thermobutyricumDSM 4928T, Clostridiumhomopropionicum DSM 5847T and Clostridium thermopalmarium DSM 5974T with 16S rRNA gene sequence similarities of 96.9, 96.6 and 96.5 %, respectively. The DNA G+C content of BXXT was 33.7 mol%, which was lower than that of C. thermobutyricum DSM 4928T (37.0 mol%) and C. thermopalmarium DSM 5974T (35.7 mol%). In addition, DSM 4928T and DSM 5974Tare thermophilic members of the genus Clostridium. The absence of C15 : 0 also distinguished BXXT from Clostridium thermobutyricum. On the basis of phylogenetic, phenotypic and chemotaxonomic evidence, the novel isolate represents a novel species within the genus Clostridium, for which the name Clostridium bovifaecis sp. nov is proposed. The type strain of the type species is BXXT (=JCM 32382T=CGMCC 1.5228T).}, } @article {pmid30058993, year = {2018}, author = {Suksaard, P and Srisuk, N and Duangmal, K}, title = {Saccharopolyspora maritima sp. nov., an actinomycete isolated from mangrove sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3022-3027}, doi = {10.1099/ijsem.0.002941}, pmid = {30058993}, issn = {1466-5034}, mesh = {Avicennia/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Humans ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Saccharopolyspora/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Saccharopolyspora strain, designated 3SS5-12T, isolated from mangrove sediment collected from Ranong Province is described. The strain was characterized by pale yellow branching aerial mycelium which differentiated into flexuous chains of spores covered with tufts of short curved hairs. The whole-cell hydrolysates of the strain contained meso-diaminopimelic acid as the diagnostic diamino acid, with arabinose, galactose and ribose as the main sugars. A major menaquinone of this strain was MK-9(H4). Mycolic acids were absent. The DNA G+C content of the genomic DNA was 69.4 mol%. The predominant cellular fatty acids were iso-C16 : 0 and anteiso-C17 : 0. Polar lipids consisted of diphosphatidylglycerol, hydroxy-phosphatidylethanolamine, hydroxy-phosphatidylmonomethylethanolamine, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, unidentified phospholipids and unidentified lipids. Phylogenetic determination based on 16S rRNA gene sequences indicated that the organism was classified in the genus Saccharopolyspora and highly similar to Saccharopolyspora jiangxiensis W12T (98.8 % sequence similarity), Saccharopolyspora hirsutasubsp. kobensis JCM 9109T (98.8 %), Saccharopolyspora antimicrobica I05-00074T (98.2 %) and Saccharopolyspora indica VRC122T (98.1 %). Evidence from the chemotaxonomic, phenotypic and molecular systematic data indicated that strain 3SS5-12T should be classified as a representing novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora maritima sp. nov. is proposed. The type strain is 3SS5-12T (=TBRC 7048T=NBRC 112863T).}, } @article {pmid30058291, year = {2018}, author = {Bahram, M and Anslan, S and Hildebrand, F and Bork, P and Tedersoo, L}, title = {Newly designed 16S rRNA metabarcoding primers amplify diverse and novel archaeal taxa from the environment.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12684}, pmid = {30058291}, issn = {1758-2229}, support = {ERC-AdG-669830//European Research Council/International ; PUT1399//Estonian Research Council/ ; PUT1317//Estonian Research Council/ ; }, abstract = {High-throughput studies of microbial communities suggest that Archaea are a widespread component of microbial diversity in various ecosystems. However, proper quantification of archaeal diversity and community ecology remains limited, as sequence coverage of Archaea is usually low owing to the inability of available prokaryotic primers to efficiently amplify archaeal compared to bacterial rRNA genes. To improve identification and quantification of Archaea, we designed and validated the utility of several primer pairs to efficiently amplify archaeal 16S rRNA genes based on up-to-date reference genes. We demonstrate that several of these primer pairs amplify phylogenetically diverse Archaea with high sequencing coverage, outperforming commonly used primers. Based on comparing the resulting long 16S rRNA gene fragments with public databases from all habitats, we found several novel family- to phylum-level archaeal taxa from topsoil and surface water. Our results suggest that archaeal diversity has been largely overlooked due to the limitations of available primers, and that improved primer pairs enable to estimate archaeal diversity more accurately.}, } @article {pmid30058280, year = {2018}, author = {Ding, JL and Peng, YJ and Chu, XL and Feng, MG and Ying, SH}, title = {Autophagy-related gene BbATG11 is indispensable for pexophagy and mitophagy, and contributes to stress response, conidiation and virulence in the insect mycopathogen Beauveria bassiana.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3309-3324}, doi = {10.1111/1462-2920.14329}, pmid = {30058280}, issn = {1462-2920}, support = {31670144//National Natural Science Foundation of China/ ; 2017YFD0200400//National Key R & D Program of China/ ; }, abstract = {Autophagy is a conserved degradation system in eukaryotic cells that includes non-selective and selective processes. Selective autophagy functions as a selective degradation mechanism for specific substrates in which autophagy-related protein 11 (ATG11) acts as an essential scaffold protein. In B. bassiana, there is a unique ATG11 family protein, which is designated as BbATG11. Disruption of BbATG11 resulted in significantly reduced conidial germination under starvation stress. The mutant ΔBbATG11 displayed enhanced sensitivity to oxidative stress and impaired asexual reproduction. The conidial yield was reduced by approximately 75%, and this defective phenotype could be repressed by increasing exogenous nutrients. The virulence of the ΔBbATG11 mutant strain was significantly impaired as indicated in topical and intra-hemocoel injection bioassays, with a greater reduction in topical infection. Notably, BbATG11 was involved in pexophagy and mitophagy, but these two autophagic processes appeared in different fungal physiological aspects. Both pexophagy and mitophagy were associated with nutrient shift, starvation stress and growth in the host hemocoel, but only pexophagy appeared in both oxidation-stressed cells and aerial mycelia. This study highlights that BbATG11 mediates pexophagy and mitophagy in B. bassiana and links selective autophagy to the fungal stress response, conidiation and virulence.}, } @article {pmid30058270, year = {2018}, author = {Bryce, C and Blackwell, N and Schmidt, C and Otte, J and Huang, YM and Kleindienst, S and Tomaszewski, E and Schad, M and Warter, V and Peng, C and Byrne, JM and Kappler, A}, title = {Microbial anaerobic Fe(II) oxidation - Ecology, mechanisms and environmental implications.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3462-3483}, doi = {10.1111/1462-2920.14328}, pmid = {30058270}, issn = {1462-2920}, support = {Emmy Noether Fellowship 326028733RTG 1708, 174858087.//Emmy-Noether fellowship (SK) and a research training group (YH)/ ; 307320//ERC/ ; FP/2007-2013//Seventh Framework Programme/ ; 326028733//DFG-funded Emmy-Noether fellowship/ ; 174858087//German Research Foundation/ ; }, abstract = {Iron is the most abundant redox-active metal in the Earth's crust. The one electron transfer between the two most common redox states, Fe(II) and Fe(III), plays a role in a huge range of environmental processes from mineral formation and dissolution to contaminant remediation and global biogeochemical cycling. It has been appreciated for more than a century that microorganisms can harness the energy of this Fe redox transformation for their metabolic benefit. However, this is most widely understood for anaerobic Fe(III)-reducing or aerobic and microaerophilic Fe(II)-oxidizing bacteria. Only in the past few decades have we come to appreciate that bacteria also play a role in the anaerobic oxidation of ferrous iron, Fe(II), and thus can act to form Fe(III) minerals in anoxic settings. Since this discovery, our understanding of the ecology of these organisms, their mechanisms of Fe(II) oxidation and their role in environmental processes has been increasing rapidly. In this article, we bring these new discoveries together to review the current knowledge on these environmentally important bacteria, and reveal knowledge gaps for future research.}, } @article {pmid30058265, year = {2018}, author = {Freitas, L and Mello, B and Schrago, CG}, title = {Multispecies coalescent analysis confirms standing phylogenetic instability in Hexapoda.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1623-1631}, doi = {10.1111/jeb.13355}, pmid = {30058265}, issn = {1420-9101}, support = {421392/2016-9//Brazilian Research Council (CNPq)/ ; 440954/2016-9//Brazilian Research Council (CNPq)/ ; 310974/2015-1//Brazilian Research Council (CNPq)/ ; }, abstract = {The multispecies coalescent (MSC) has been increasingly used in phylogenomic analyses due to the accommodation of gene tree topological heterogeneity by taking into account population-level processes, such as incomplete lineage sorting. In this sense, the phylogeny of insect species, which are characterized by their large effective population sizes, is suitable for a coalescent-based analysis. Furthermore, studies so far recovered short internal branches at early divergences of the insect tree of life, indicating fast evolutionary radiations that increase the probability of incomplete lineage sorting in deep time. Here, we investigated the performance of the MSC for a phylogenomic data set of hexapods compiled by Misof et al. (2014, Science 346:763). Our analysis recovered the monophyly of most insect orders, and major phylogenetic relationships were in agreement with current insect systematics. We identified, however, some evolutionary associations that were consistently problematic. Most noticeable, Hexapod monophyly was disrupted by the sister group relationship between the remiped crustacean and Insecta. Additionally, the interordinal relationships within Polyneoptera and Neuropteroidea were found to be phylogenetically unstable. We show that these controversial phylogenetic arrangements were also poorly supported by previous analyses, and therefore, we evaluated their robustness to stochastic errors from sampling sites and terminals, confirming standing problems in hexapod phylogeny in the genomics age.}, } @article {pmid30058121, year = {2018}, author = {Xu, T and Cao, H and Zhu, W and Wang, M and Du, Y and Yin, Z and Chen, M and Liu, Y and Yang, B and Liu, B}, title = {RNA-seq-based monitoring of gene expression changes of viable but non-culturable state of Vibrio cholerae induced by cold seawater.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {594-604}, doi = {10.1111/1758-2229.12685}, pmid = {30058121}, issn = {1758-2229}, abstract = {Vibrio cholerae O1 is a natural inhabitant of aquatic environments and causes the acute diarrheal disease cholera. Entry into a viable but non-culturable (VBNC) state is a survival strategy by which V. cholerae withstands natural stresses and is important for the transition between the aquatic and host environments during the V. cholerae life cycle. In this study, the formation of VBNC V. cholerae induced by cold seawater exposure was investigated using RNA sequencing (RNA-seq). The analysis revealed that the expression of 1420 genes was changed on VBNC state formation. In the VBNC cells, genes related to biofilm formation, chitin utilization and stress responses were upregulated, whereas those related to cell division, morphology and ribosomal activity were mainly downregulated. The concurrent acquisition of a carbon source and the arrest of cell division in cells with low metabolic activity help bacteria increase their resistance to unfavourable environments. Moreover, two transcriptional regulators, SlmA and MetJ, were found to play roles in both VBNC formation and intestinal colonization, suggesting that some genes may function in both processes. This acquired knowledge will improve our understanding of the molecular mechanisms of stress tolerance and may help control future cholera infections and outbreaks.}, } @article {pmid30058118, year = {2018}, author = {Friedrich, M and Chahine, H and Al-Jageta, C and Badreddine, H}, title = {Massive parallel expansions of Methuselah/Methuselah-like receptors in schizophoran Diptera.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {6-7}, pages = {384-389}, doi = {10.1002/jez.b.22813}, pmid = {30058118}, issn = {1552-5015}, abstract = {The Methuselah/Methuselah-like (Mth/Mthl) family of G-protein coupled receptors (GPCRs) is represented by 16 homologs in the fruit fly Drosophila melanogaster. Three of them have thus far been functionally characterized and found to play critical roles in cell adhesion, immunity, lifespan, and oxidative stress regulation. Evolutionary studies have shown that the large number of D. melanogaster Mth/Mthl GPCRs arose by at least two rounds of gene duplications. The first produced the "mth superclade" subfamily and was followed by the expansion of the "melanogaster subgroup" cluster within the "mth superclade" of Mth/Mthl GPCRs. The adaptive significance of the Mth/Mthl receptor repertoire expansion in Drosophila remains elusive. Studying the Mth/Mthl gene family content in newly available dipteran genomes, we find that the first expansion of the mthl superclade predates the diversification of schizophoran Diptera approximately 65 million years ago. Unexpectedly, we further find that the subsequent expansion of the melanogaster subgroup cluster was paralleled by independent mth superclade Mth/Mthl GPCR expansions in other schizophoran clades (Muscidae and Tephritidae). Our study thus reveals an even more dynamic diversification of mth superclade GPCRs than previously appreciated and linked to the emergence of schizophoran flies, the most dramatic radiation in the dipteran tree of life.}, } @article {pmid30058114, year = {2018}, author = {Santamaría-Hernando, S and Rodríguez-Herva, JJ and Martínez-García, PM and Río-Álvarez, I and González-Melendi, P and Zamorano, J and Tapia, C and Rodríguez-Palenzuela, P and López-Solanilla, E}, title = {Pseudomonas syringae pv. tomato exploits light signals to optimize virulence and colonization of leaves.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4261-4280}, doi = {10.1111/1462-2920.14331}, pmid = {30058114}, issn = {1462-2920}, support = {H2020-ICT-2015-688135//European Union H2020 LEIT Information and Communication Technologies/ ; AGL22015-63851-R//Ministerio de Economía y Competitividad/ ; }, abstract = {Light is pervasive in the leaf environment, creating opportunities for both plants and pathogens to cue into light as a signal to regulate plant-microbe interactions. Light enhances plant defences and regulates opening of stomata, an entry point for foliar bacterial pathogens such as Pseudomonas syringae pv. tomato DC3000 (PsPto). The effect of light perception on gene expression and virulence was investigated in PsPto. Light induced genetic reprogramming in PsPto that entailed significant changes in stress tolerance and virulence. Blue light-mediated up-regulation of type three secretion system genes and red light-mediated down-regulation of coronatine biosynthesis genes. Cells exposed to white light, blue light or darkness before inoculation were more virulent when inoculated at dawn than dusk probably due to an enhanced entry through open stomata. Exposure to red light repressed coronatine biosynthesis genes which could lead to a reduced stomatal re-opening and PsPto entry. Photoreceptor were required for the greater virulence of light-treated and dark-treated PsPto inoculated at dawn as compared to dusk, indicating that these proteins sense the absence of light and contribute to priming of virulence in the dark. These results support a model in which PsPto exploits light changes to maximize survival, entry and virulence on plants.}, } @article {pmid30058099, year = {2018}, author = {Liu, Q and Liu, Y and Kang, Z and Xiao, D and Gao, C and Xu, P and Ma, C}, title = {2,3-Butanediol catabolism in Pseudomonas aeruginosa PAO1.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3927-3940}, doi = {10.1111/1462-2920.14332}, pmid = {30058099}, issn = {1462-2920}, support = {31670041//National Natural Science Foundation of China/ ; 31470164//National Natural Science Foundation of China/ ; 2017A010105020//Special Funds for Public Welfare Research and Capacity Building in Guangdong Province of China/ ; 2015WLJH25//Young Scholars Program of Shandong University/ ; JQ 201806//Shandong Provincial Funds for Distinguished Young Scientists/ ; }, abstract = {2,3-Butanediol (2,3-BD) is a primary microbial metabolite that enhances the virulence of Pseudomonas aeruginosa and alters the lung microbiome. 2,3-BD exists in three stereoisomeric forms: (2R,3R)-2,3-BD, meso-2,3-BD and (2S,3S)-2,3-BD. In this study, we investigated whether and how P. aeruginosa PAO1 utilizes these 2,3-BD stereoisomers and showed that all three stereoisomers were transformed into acetoin by (2R,3R)-2,3-butanediol dehydrogenase (BDH) or (2S,3S)-2,3-BDH. Acetoin was cleaved to form acetyl-CoA and acetaldehyde by acetoin dehydrogenase enzyme system (AoDH ES). Genes encoding (2R,3R)-2,3-BDH, (2S,3S)-2,3-BDH and the E1 and E2 components of AoDH ES were identified as part of a new 2,3-BD utilization operon. In addition, the regulatory protein AcoR promoted the expression of this operon using acetaldehyde, a cleavage product of acetoin, as its direct effector. The results of this study elucidate the integrated catabolic role of 2,3-BD and may provide new insights in P. aeruginosa-related infections.}, } @article {pmid30057348, year = {2018}, author = {Osakunor, DNM and Sengeh, DM and Mutapi, F}, title = {Universal Health Coverage in Africa: Coinfections and Comorbidities.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {813-817}, doi = {10.1016/j.pt.2018.07.002}, pmid = {30057348}, issn = {1471-5007}, mesh = {Africa ; *Coinfection ; *Comorbidity ; Humans ; National Health Programs/trends ; Universal Health Insurance/standards/*statistics & numerical data/trends ; World Health Organization ; }, abstract = {At the 67th session of the World Health Organization (WHO) Regional Committee meeting in August 2017, African health ministers adopted a range of transformational actions intended to strengthen health systems in countries, leading to Universal Health Coverage (UHC). A critical challenge for UHC is the existence of coinfections and noncommunicable diseases (NCDs), characterised by comorbidities.}, } @article {pmid30057327, year = {2018}, author = {Rector, AL and Vergamini, M}, title = {Forelimb morphology and substrate use in extant Cercopithecidae and the fossil primate community of the Hadar sequence, Ethiopia.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {70-83}, doi = {10.1016/j.jhevol.2018.06.005}, pmid = {30057327}, issn = {1095-8606}, abstract = {It is suggested that joint architecture of the extant cercopithecid forelimb differentiates terrestrial from arboreal quadrupedal species. Linear dimensions of forelimb joint morphology have also been used to assign fossil species to locomotor categories. However, many primates use a mix of terrestrial and arboreal behaviors, which can be problematic when developing models of behavior reconstruction using morphological variation. The current study uses multivariate analyses to identify morphology related to substrate use in primates, including determination of semiterrestriality. Measurements collected from distal humeri and proximal ulnae of 49 extant cercopithecid primate species were selected based on studies indicating that they could individually predict substrate use. Analyses including one-way analysis of variance, principal components, and discriminant functions were conducted to assess their ability to differentiate between arboreal and terrestrial substrate use. The functions created in these analyses are then applied to data from fossil specimens from the Hadar sequence, Ethiopia, sampling both the Hadar and overlying Busidima Formations, to retrodict possible substrate behavior of fossil monkeys at Hadar through time. As this study is designed to identify function and behavior rather than phylogeny, the taxonomic assignment of the fossil specimens is sometimes uncertain, but substrate behavior can still be inferred. Results suggest that substrate use, including semiterrestrial behavior, in extant and extinct primates can be inferred successfully from multivariate analyses based on joint morphology of the monkey elbow. This study reveals that the ecological distribution of primarily terrestrial fossil primate species of the Hadar sequence is comparable to modern-day communities in habitats similar to those reconstructed for the Hadar members.}, } @article {pmid30057326, year = {2018}, author = {Pampush, JD and Scott, JE and Robinson, CA and Delezene, LK}, title = {Oblique human symphyseal angle is associated with an evolutionary rate-shift early in the hominin clade.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {84-95}, doi = {10.1016/j.jhevol.2018.06.006}, pmid = {30057326}, issn = {1095-8606}, abstract = {The rate of change in primate mandibular symphyseal angles was modeled with particular aim of locating a rate-shift within the hominin clade. Prior work noted that the human symphyseal angle must have experienced a rapid rate of change in order to assume the modern human form, suggestive of the non-random work of natural selection. This study indicates that the rate of symphyseal evolution rose dramatically between Australopithecus anamensis and Australopithecus afarensis and continued throughout the diversification of the hominin clade. Noting the timing of this event, we speculate as to what ecological factors could have been at play in driving this rearrangement of the anterior mandible, contributing to the eventual appearance of the human chin.}, } @article {pmid30057325, year = {2018}, author = {Pugh, KD and Gilbert, CC}, title = {Phylogenetic relationships of living and fossil African papionins: Combined evidence from morphology and molecules.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {35-51}, doi = {10.1016/j.jhevol.2018.06.002}, pmid = {30057325}, issn = {1095-8606}, abstract = {African papionins are a highly successful subtribe of Old World monkeys with an extensive fossil record. On the basis of both molecular and morphological data, crown African papionins are divided into two clades: Cercocebus/Mandrillus and Papio/Lophocebus/Rungwecebus/Theropithecus (P/L/R/T), though phylogenetic relationships in the latter clade, among both fossil and extant taxa, remain difficult to resolve. While previous phylogenetic studies have focused on either molecular or morphological data, here African papionin molecular and morphological data were combined using both supermatrix and molecular backbone approaches. Theropithecus is supported as the sister taxon to Papio/Lophocebus/Rungwecebus, and while supermatrix analyses using Bayesian methods are largely unresolved, analyses using parsimony are broadly similar to earlier studies. Thus, the position of Rungwecebus relative to Papio and Lophocebus remains equivocal, possibly due to complex patterns of reticulation. Parapapio is likely a paraphyletic grouping of primitive African papionins or possibly a collection of stem P/L/R/T taxa, and a similar phylogenetic position is also hypothesized for Pliopapio. ?Papio izodi is either a stem or crown P/L/R/T taxon, but does not group with other Papio taxa. Dinopithecus and Gorgopithecus are also stem or crown P/L/R/T taxa, but their phylogenetic positions remain unstable. Finally, T. baringensis is likely the most basal Theropithecus taxon, with T. gelada and T. oswaldi sister taxa to the exclusion of T. brumpti. By integrating large amounts of molecular and morphological data, combined with the application of updated parsimony and Bayesian methods, this study represents the most comprehensive analysis of African papionin phylogenetic history to date.}, } @article {pmid30057183, year = {2018}, author = {Rodriguez-Terrones, D and Torres-Padilla, ME}, title = {Nimble and Ready to Mingle: Transposon Outbursts of Early Development.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {10}, pages = {806-820}, doi = {10.1016/j.tig.2018.06.006}, pmid = {30057183}, issn = {0168-9525}, abstract = {Transposable elements are the largest individual constituent of mammalian genomes. These elements are highly diverse, a consequence of the multiplicity of genomic habitats that they inhabit and of the complex evolutionary histories that they have developed therein. Intriguingly, a surge of transposable element transcription occurs during mammalian preimplantation development, contributing to the establishment of totipotency and pluripotency and to the activation of the embryonic genome. However, it remains an open question how such an evolutionarily divergent set can mediate such conserved developmental processes. Here, we review transposable element diversity across mammals and their evolutionary significance. We also discuss the implications that their high evolutionary divergence has for the regulation of preimplantation development across mammals.}, } @article {pmid30056935, year = {2018}, author = {Lim, W and Bae, H and Bazer, FW and Song, G}, title = {Characterization of C-C motif chemokine ligand 4 in the porcine endometrium during the presence of the maternal-fetal interface.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {146-158}, doi = {10.1016/j.ydbio.2018.06.022}, pmid = {30056935}, issn = {1095-564X}, mesh = {Animals ; Cell Proliferation/physiology ; Chemokine CCL4/*metabolism ; Embryo Implantation/*physiology ; Endometrium/*metabolism ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Female ; MAP Kinase Signaling System/*physiology ; Phosphatidylinositol 3-Kinases/metabolism ; Placenta/*metabolism ; Pregnancy/*metabolism ; Receptors, CCR5/metabolism ; Swine/*embryology ; }, abstract = {Chemokines and their receptors play a crucial role in embryo implantation at the maternal-fetal interface during pregnancy. In this study, we investigated the role of CCL4 in development of the porcine endometrium in the early gestational period. Porcine CCL4 showed high similarity with the human counterpart, and mRNA expression of CCL4 and its receptor (CCR5) was predominantly present in the endometrium during early pregnancy. Treatment with CCL4 increased proliferation of porcine uterine luminal epithelial (pLE) cells by activation of PI3K and MAPK signal transduction. In addition, CCL4 recovered the endoplasmic-reticulum stress-reduced proliferation and decreased the unfolded protein response in pLE cells. Besides, the lipopolysaccharide-activated NF-κB pathway was suppressed in response to CCL4 in pLE cells. Inhibition of CCR5 decreased the proliferation of pLE cells and activation of the PI3K and MAPK pathways by CCL4. Furthermore, CCL4 enhanced conceptus-maternal interactions between porcine trophectoderm (pTr) cells and pLE cells during early pregnancy by activating expression of migration and implantation-related genes. Collectively, the results suggest that CCL4 may improve successful implantation in early pregnancy in pigs.}, } @article {pmid30056932, year = {2018}, author = {Ramey-Balcı, P and Fiege, D and Struck, TH}, title = {Molecular phylogeny, morphology, and distribution of Polygordius (Polychaeta: Polygordiidae) in the Atlantic and Mediterranean.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {919-930}, doi = {10.1016/j.ympev.2018.06.039}, pmid = {30056932}, issn = {1095-9513}, abstract = {Low morphological diversity among interstitial taxa makes it difficult to delimit species and their geographic boundaries based solely on morphology and molecular data often reveal cryptic species. Polygordius (Annelida, Polygordiidae) have low morphological diversity, but are unusual among interstitial species in their comparatively large size due to their elongated form, high fecundity, and potential for long-distance dispersal via a planktotrophic larval stage. Polygordius species collected from 14 localities in the Northwest Atlantic, Mediterranean Sea, and Southwest Atlantic including several of the respective type localities were analysed. This study presents the first phylogeny of the genus Polygordius and combines molecular data, sequences of COI, 16S and ITS1/2 genes, and morphological data for a systematic re-evaluation focusing on Atlantic species, with an emphasis on populations from European waters. Phylogenetic analyses recovered six valid species (P. appendiculatus, P. lacteus, P. neapolitanus, P. triestinus, P. jouinae, and P. eschaturus) and their distinctness is confirmed by haplotype network analyses. Thus, molecular data supported the validity of the previously recognized morpho-species and no new species were present. P. erythrophthalmus and P. villoti are invalid species being synonymous with P. lacteus. Subtle differences in head and pygidial morphology and larval type (endolarva vs. exolarva), were useful characters for discrimination. Yet seemingly significant variation in characters among individuals in some species was not diagnostic (e.g., number of pygidial cirri). Highly similar species based on adult morphology were shown to be sister taxa occurring in allopatry. Present day distribution patterns of species are summarized in light of this study.}, } @article {pmid30056833, year = {2018}, author = {Mercer, F and Johnson, PJ}, title = {Trichomonas vaginalis: Pathogenesis, Symbiont Interactions, and Host Cell Immune Responses.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {683-693}, doi = {10.1016/j.pt.2018.05.006}, pmid = {30056833}, issn = {1471-5007}, mesh = {Humans ; Immunity, Cellular/*immunology ; *Symbiosis ; Trichomonas Infections/*immunology/*pathology ; Trichomonas vaginalis/*immunology ; }, abstract = {The parasite Trichomonas vaginalis (Tv) causes a highly prevalent sexually transmitted infection. As an extracellular pathogen, the parasite mediates adherence to epithelial cells to colonize the human host. In addition, the parasite interfaces with the host immune system and the vaginal microbiota. Modes of Tv pathogenesis include damage to host tissue mediated by parasite killing of host cells, disruption of steady-state vaginal microbial ecology, and eliciting inflammation by activating the host immune response. Recent Tv research has uncovered new players that contribute to multifactorial mechanisms of host-parasite adherence and killing, and has examined the relationship between Tv and vaginal bacteria. Mechanisms that may lead to parasite recognition and killing, or the evasion of host immune cells, have also been revealed.}, } @article {pmid30056594, year = {2018}, author = {Yamauchi, K and Kasai, K}, title = {Sequential Molecular Events of Functional Trade-Offs in 5-Hydroxyisourate Hydrolase Before and After Gene Duplication Led to the Evolution of Transthyretin During Chordate Diversification.}, journal = {Journal of molecular evolution}, volume = {86}, number = {7}, pages = {457-469}, pmid = {30056594}, issn = {1432-1432}, abstract = {Transthyretin (TTR), a plasma thyroid hormone distributor protein (THDP), emerged from 5-hydroxyisourate hydrolase (HIUHase), an enzyme involved in urate metabolism, by gene duplication at a stage of chordate evolution. Comparison of amino acid sequences revealed the presence of two His-rich segments in the primitive TTRs. Using several HIUHase and TTR mutants, we investigated 5-hydroxyisourate (HIU) hydrolysis activity and thyroid hormone (TH) binding activity to elucidate how a novel function as a THDP arose. Lancelet HIUHase was found to have higher enzyme activity than trout HIUHase. Two amino acid substitutions, R54E/Y119T, at the active sites of HIUHase, exerted weak [125I]-3,3',5-triiodo-L-thyronine ([125I]T3) binding activity with a concomitant loss of HIU hydrolysis activity. Addition of 3×His (3×H) to the N-terminal end weakened HIU hydrolysis activity of both lancelet and trout HIUHases, whereas it enhanced T3-binding activity of HIUHase R54E/Y119T. Trout HIUHase 3×H R54E/Y119T had higher [125I]T3-binding activity than that of lancelet HIUHase 3×H R54E/Y119T, with a Kd of 143 nM, and displayed metal dependency and no TH binding specificity. Deletion of the N-terminal His-rich segment from lamprey TTR decreased T3-binding activity, while addition of 3×H to trout TTR increased T3-binding activity, while maintaining TH binding specificity. Our results suggest that functional trade-offs of HIU hydrolysis activity with TH binding activity might have sequentially occurred before and after gene duplication, and that TH binding specificity and high-affinity sites may have been acquired later in the course of TTR evolution.}, } @article {pmid30056329, year = {2018}, author = {Mooser, C and Gomez de Agüero, M and Ganal-Vonarburg, SC}, title = {Standardization in host-microbiota interaction studies: challenges, gnotobiology as a tool, and perspective.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {50-60}, doi = {10.1016/j.mib.2018.07.007}, pmid = {30056329}, issn = {1879-0364}, abstract = {Considering the increasing list of diseases linked to the commensal microbiota, experimental studies of host-microbe interactions are of growing interest. Axenic and differently colonized animal models are inalienable tools to study these interactions. Factors, such as host genetics, diet, antibiotics and litter affect microbiota composition and can be confounding factors in many experimental settings. The use of gnotobiotic mice harboring defined microbiotas of different complexity plus additional housing standardization have thus become a gold standard to study the influence of the microbiome on the host. We highlight here the recent advances, challenges and outstanding goals in gnotobiology with the ambition to contribute to the generation of reliable, reproducible and transferrable results, which form the basis for advances in biomedical research.}, } @article {pmid30055910, year = {2018}, author = {Bailey, NW and Moore, AJ}, title = {Evolutionary Consequences of Social Isolation.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {595-607}, doi = {10.1016/j.tree.2018.05.008}, pmid = {30055910}, issn = {1872-8383}, abstract = {Social isolation has profound impacts. Most animal research focuses on negative phenotypic consequences of social isolation within individual lifetimes. Less is known about how it affects genetics, selection, and evolution over longer timescales, though ample indirect evidence suggests that it might. We advocate that evolutionary consequences of social isolation be tested more directly. We suggest that the 'index of social isolation', the mismatch between actual and optimal social interaction experienced by individuals within a population, may play a key role in releasing cryptic genetic variation, adaptation rates, diversification patterns, and ecosystem-level processes. Evolutionary dynamics arising from social isolation could have significant impacts in applied settings such as conservation, animal breeding, control of biological invasions, and evolutionary resilience to anthropogenic change.}, } @article {pmid30055656, year = {2018}, author = {Almeida, IS and Wickramasinghe, D and Weerakkody, P and Samarasekera, DN}, title = {Treatment of fistula in-ano with fistula plug: experience of a tertiary care centre in South Asia and comparison of results with the West.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {513}, pmid = {30055656}, issn = {1756-0500}, mesh = {Adult ; Asia ; Female ; Humans ; Male ; Prospective Studies ; Rectal Fistula/*surgery ; Retrospective Studies ; Tertiary Care Centers ; Treatment Outcome ; }, abstract = {OBJECTIVES: Surgery for fistula in ano is associated with anal incontinence. The biologic anal fistula plug (AFP) can minimize this. This is a retrospective analysis of patients with cryptoglandular anorectal fistulae, who underwent a surgical procedure using AFP. Patient's demographics and characteristics of the fistulae were obtained from a prospective database. Each primary opening was occluded by using an AFP. Success was defined by the closure of the external opening and absent drainage.

RESULTS: Fifty-one patients were treated with AFP (male:female: 37:14), mean age 42 years (SD ± 14.86, range 26-70). Ten patients defaulted follow-up. Forty-seven procedures were analysed. Twenty-three (56.1%) patients had complete healing while 18 (43.9%) patients failed the fistula plug procedure during the follow up period of 12 months. Logistical regression failed to identify any statistical significant association with demographic or disease factors and healing. Healing was 1.5 times less likely for every failed procedure prior to AFP insertion. Contrary to other published studies, placement of fistula plug was associated with much lower overall rates of fistula healing. Highest success rates were seen in simple fistulae when compared to the complex type. Repeat plug placement may be successful in selected patients.}, } @article {pmid30055654, year = {2018}, author = {Maraiki, F and Kelly, S and Ahmed, M and Balhareth, S and Elhasan, T and Aljurf, M and Bazarbashi, S}, title = {Utilization and cost of electronic resources in adult cancer center.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {516}, pmid = {30055654}, issn = {1756-0500}, mesh = {Adult ; Cancer Care Facilities/economics/*statistics & numerical data ; Delivery of Health Care ; Electronic Health Records/*statistics & numerical data ; Health Resources/*economics ; Humans ; Medical Oncology/*economics ; Pharmacists ; Physicians ; }, abstract = {OBJECTIVES: This study aims to evaluate the knowledge of healthcare providers and the cost of the current institutional e-resources in an adult oncology setting. To assess the awareness, accessibility, and utilization of the available intranet e-resources, a survey questionnaire was distributed to all oncology healthcare practitioners (physicians, nurses, and pharmacists) in an adult oncology center. The e-resources were divided into two main categories: pre-paid and institution-specific. The cost of the pre-paid e-resources was obtained from the relevant department. The cost of the institution-specific e-resources was calculated based on the human cost spent developing these e-resources; the cost of the information technology (IT) and the organizational overhead were also taken into consideration.

RESULTS: Institution-specific e-resources constituted the majority (62%) versus (38%) for pre-paid. The overall awareness, access, and frequent utilization of institution-specific e-resources, as compared to pre-paid e-resources, were low (< 50%). The cost of the institution-specific e-resources was $1,137,196, which was more than ten times higher than the pre-paid e-resources. This study identifies the general lack of awareness and utilization of institutional e-resources. The low utilization coupled with the high cost of the institution-specific e-resources makes pre-paid e-resources an attractive alternative for any institution.}, } @article {pmid30055653, year = {2018}, author = {Amrud, K and Slinger, R and Sant, N and Desjardins, M and Toye, B}, title = {A comparison of the Allplex™ bacterial and viral assays to conventional methods for detection of gastroenteritis agents.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {514}, pmid = {30055653}, issn = {1756-0500}, mesh = {Bacteriological Techniques/methods ; Escherichia coli/genetics/*isolation & purification ; Escherichia coli Infections/diagnosis ; Feces ; Gastroenteritis/*microbiology ; Humans ; *Multiplex Polymerase Chain Reaction ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Molecular methods to detect diarrheal pathogens are increasingly being used in place of conventional methods. We compared a new multiplex real-time PCR assay for detection of both bacterial and viral gastroenteritis agents, the Allplex™ Gastrointestinal Panel Assays (AGPA), to conventional methods (stool culture for bacterial pathogens and electron microscopy (EM) for viral pathogens).

RESULTS: Gastrointestinal viruses, in particular norovirus genogroup II viruses, were detected by the AGPA in a high number of specimens that were negative by EM. For bacterial pathogens, the AGPA was able to detect the organisms grown in culture with high sensitivity and additionally detected several types of E. coli, such as enteropathogenic E. coli (EPEC), enteroaggregative E. coli (EAEC), and non-O157 Shiga toxin-producing E. coli (STEC), that could not be detected with conventional culture methods. Overall, the AGPA had a > 2-fold higher detection rate than the conventional methods, with 24/135 (17.8%) samples positive by conventional methods and 60/135 (44.4%) by AGPA. Thus, diarrhea pathogen detection rates increased substantially with the use of the AGPA as compared to conventional methods.}, } @article {pmid30055652, year = {2018}, author = {Mbanga, CM and Efie, DT and Aroke, D and Njim, T}, title = {Prevalence and predictors of recreational drug use among medical and nursing students in Cameroon: a cross sectional analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {515}, pmid = {30055652}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cameroon/epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Prevalence ; *Street Drugs ; *Students, Medical ; *Students, Nursing ; Substance-Related Disorders/*epidemiology ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Medical and nursing students in Cameroon are likely to have mental health problems given the stressful nature of their studies. Paucity of mental health institutions in the country implies they hardly get access to professional help when needed and are obliged to develop coping strategies such as recreational drug use. This study aims to determine the prevalence and predictors of recreational drug use among a group of Cameroonian medical and nursing students.

RESULTS: Cross-sectional analysis of 852 medical and nursing students (mean age 21.78 ± 3.14, 31.49% males) recruited by convenience sampling from three state-owned medical schools; and from two state-owned and two private nursing schools in Cameroon over a four-month period (January-April 2018). Information was collected via a printed self-administered and structured questionnaire from consenting students. Multivariable logistic regression analysis was used to identify independent predictors of recreational drug use. The overall prevalence of recreational drug use was 1.64% with tramadol and marijuana noted as the drugs used by these students. Independent predictors of recreational drug use were: presence of a chronic illness (OR 5.26; 95% CI 1.32, 20.97; p = 0.019), alcohol consumption (OR 5.08; 95% CI 1.54, 16.73; p = 0.008) and Total Oldenburg Burnout Inventory score (OR 1.11; 95% CI 1.02, 1.21; p = 0.021). The use of recreational drugs by medical and nursing students in Cameroon remains worrisome despite its very low prevalence, as it may negatively impact their performance and health.}, } @article {pmid30055650, year = {2018}, author = {Pérez-González, A and Caro, E}, title = {Effect of transcription terminator usage on the establishment of transgene transcriptional gene silencing.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {511}, pmid = {30055650}, issn = {1756-0500}, support = {BIO2014-58789-P//Ministerio de Economía y Competitividad/ ; RYC-2012-10367//Ministerio de Economía y Competitividad/ ; Contarto pre-doctoral Programa Propio-Santander Universidades//Universidad Politécnica de Madrid/ ; }, mesh = {Arabidopsis/genetics ; *DNA Methylation ; Gene Expression Regulation, Plant ; *Gene Silencing ; *Genes, Reporter ; Plants, Genetically Modified ; Promoter Regions, Genetic ; Transcription, Genetic ; *Transgenes ; }, abstract = {OBJECTIVE: Obtaining high and stable transgene expression is of vital importance for plant genetic engineering. A lot is known about the relationship between terminator efficiency and gene expression, but no studies have addressed the relationship between terminator usage and transgene expression stability or heritable gene silencing. In this paper, we aim to analyze if terminators are a determining factor in the establishment of promoter DNA methylation of plant transgenes.

RESULTS: Our experiments comparing plants with a LUC reporter under the 35S CaMV promoter and good efficiency terminators (Thsp, T35S) show that the use of efficient terminator sequences does not avoid the accumulation of promoter DNA methylation and transgene silencing. However, Thsp lead to a higher reporter gene expression and lower promoter DNA methylation levels than T35S, supporting that terminator usage is indeed involved in the establishment of TGS by methylation of transgenes' promoters. In the case of a terminatorless construct, the PTGS initiated by the improperly terminated mRNAs is not followed by the establishment of heritable silencing in the form of strong promoter DNA methylation, like in the case of TAS genes and reactivated TEs (for the transgene DNA methylation levels remained below the 20%).}, } @article {pmid30055649, year = {2018}, author = {Alshareef, SA and Rayis, DA and Adam, I and Gasim, GI}, title = {Helicobacter pylori infection, gestational diabetes mellitus and insulin resistance among pregnant Sudanese women.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {517}, pmid = {30055649}, issn = {1756-0500}, mesh = {Adult ; Blood Glucose ; Cross-Sectional Studies ; Diabetes, Gestational/*epidemiology ; Female ; Glucose Tolerance Test ; Helicobacter Infections/*complications ; Helicobacter pylori ; Humans ; Insulin ; *Insulin Resistance ; Pregnancy ; *Pregnancy Complications, Infectious ; Seroepidemiologic Studies ; }, abstract = {OBJECTIVES: To assess the association between Helicobacter pylori (H. pylori) infection and insulin resistance among pregnant Sudanese women attending Saad Abuelela hospital (Khartoum). A cross-sectional study was conducted from 1st July 2017 to 31st January 2018. One hundred and sixty-six women were enrolled and underwent testing for H. pylori IgG antibodies using specific ELISA kits. The Quantitative insulin sensitivity check index (QUICKI) was computed from the fasting insulin and glucose levels.

RESULTS: Median age, gravidity and gestational age were 27 years, 2 and 26 weeks, respectively. Twenty (12%) women were found to have gestational diabetes mellitus (GDM). H. pylori IgG seroprevalence was 66.0% among the study population. Univariate analysis showed that H. pylori-seropositivity was significantly higher among women who have GDM while Log (Homeostatic Model Assessment-β) HOMA-B% was lower (P value = 0.038, and 0.028) respectively. There was no difference between the GDM group and the other group in terms of demographics, body mass index, haemoglobin and QUICKI index results. In multivariate analysis, a higher prevalence of H. pylori was associated with GDM (OR = 2.8, 95% CI 1.1-7.5, P = 0.036). The current study concludes that an increased prevalence of H. pylori is a risk factor for the development of GDM.}, } @article {pmid30055648, year = {2018}, author = {Fischer-Huchzermeyer, S and Chikobava, L and Stahn, V and Zangarini, M and Berry, P and Veal, GJ and Senner, V and Mautner, VF and Harder, A}, title = {Testing ATRA and MEK inhibitor PD0325901 effectiveness in a nude mouse model for human MPNST xenografts.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {520}, pmid = {30055648}, issn = {1756-0500}, support = {604242//Nothing is forever e.V./ ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Benzamides/*pharmacology ; Diphenylamine/*analogs & derivatives/pharmacology ; Heterografts ; Humans ; Mice ; Mice, Nude ; Nerve Sheath Neoplasms/*drug therapy ; Neurilemmoma ; Sarcoma/*drug therapy ; }, abstract = {OBJECTIVE: Malignant peripheral nerve sheath tumors (MPNST) are aggressive sarcomas characterized by high recurrence rates and early metastases. These tumors arise more frequently within neurofibromatosis type 1 (NF1) and present with resistance during standard chemotherapy leading to increased mortality and morbidity in those patients. In vitro all-trans retinoic acid (ATRA) and MEK inhibitors (MEKi) were shown to inhibit tumor proliferation, especially when applied in combination. Therefore, we established a nude mouse model to investigate if treatment of xenografts derived from NF1 associated S462 and T265 MPNST cells respond to ATRA and the MEKi PD0325901.

RESULTS: We demonstrated that human NF1 associated MPNST derived from S462 but not T265 cells form solid subcutaneous tumors in Foxn1 nude mice but not in Balb/c, SHO or Shorn mice. We verified a characteristic staining pattern of human MPNST xenografts by immunohistochemistry. Therapeutic effects of ATRA and/or MEKi PD0325901 on growth of S462 MPNST xenografts in Foxn1 nude mice were not demonstrated in vitro, as we did not observe significant suppression of MPNST growth compared with placebo treatment.}, } @article {pmid30055647, year = {2018}, author = {Marek, AP and Nygaard, RM and Cohen, EM and Polites, SF and Sirany, AE and Wildenberg, SE and Elsbernd, TA and Murphy, S and Dean Potter, D and Zielinski, MD and Richardson, CJ}, title = {Rural versus urban pediatric non-accidental trauma: different patients, similar outcomes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {519}, pmid = {30055647}, issn = {1756-0500}, mesh = {Adolescent ; Child ; Child, Preschool ; Humans ; Infant ; Infant, Newborn ; Injury Severity Score ; Male ; Retrospective Studies ; *Rural Population ; Trauma Centers ; *Urban Population ; Wounds and Injuries/*epidemiology/therapy ; }, abstract = {OBJECTIVE: Our aim was to compare urban and rural non-accidental trauma for trends and characterize where injury prevention efforts can be focused. Pediatric trauma patients (age 0-14 years) at two level I adult and pediatric trauma centers, one rural and one urban, were included and data from the trauma registries at each center was abstracted.

RESULTS: Of 857 pediatric admissions, 10% of injuries were considered non-accidental. The mean age for all non-accidental trauma patients was significantly lower than the overall pediatric trauma population (2.6 vs. 7.7 years, P < 0.001). Significantly more fatalities occurred in the non-accidental trauma cohort (5.7% vs. 1% P = 0.007). In nearly half of all non-accidental trauma patients, the primary insurance was government programs (49%) and 46% were commercial insurance. The proportion of government insurance in non-accidental trauma was higher in both urban and rural cohorts. There were similar rates of urban and rural patients sustaining non-accidental trauma who were uninsured (6.5 vs. 5.3%). Patients that were younger, in a rural location, and receiving government insurance were at higher risk of non-accidental trauma on univariable analysis. However, only age remained an independent predictor on multivariable analysis.}, } @article {pmid30055643, year = {2018}, author = {Wiegreffe, D and Müller, L and Steuck, J and Zeckzer, D and Stadler, PF}, title = {The Sierra Platinum Service for generating peak-calls for replicated ChIP-seq experiments.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {512}, pmid = {30055643}, issn = {1756-0500}, support = {01IS14014B//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Chromatin Immunoprecipitation ; *High-Throughput Nucleotide Sequencing ; Quality Control ; *Sequence Analysis, DNA ; }, abstract = {OBJECTIVE: Sierra Platinum is a fast and robust peak-caller for replicated ChIP-seq experiments with visual quality-control and -steering. The required computing resources are optimized but still may exceed the resources available to researchers at biological research institutes.

RESULTS: Sierra Platinum Service provides the full functionality of Sierra Platinum: using a web interface, a new instance of the service can be generated. Then experimental data is uploaded and the computation of the peaks is started. Upon completion, the results can be inspected interactively and then downloaded for further analysis, at which point the service terminates.}, } @article {pmid30055628, year = {2018}, author = {Telles, S and Gupta, RK and Verma, S and Kala, N and Balkrishna, A}, title = {Changes in vigilance, self rated sleep and state anxiety in military personnel in India following yoga.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {518}, pmid = {30055628}, issn = {1756-0500}, mesh = {Adult ; Anxiety ; Humans ; India ; Longitudinal Studies ; Male ; Middle Aged ; Military Personnel/*psychology ; Self Report ; *Sleep ; *Yoga ; Young Adult ; }, abstract = {OBJECTIVES: To study the effects of 9 days of yoga on self-rated sleep, state anxiety and performance in a vigilance test among border security force (BSF) personnel. Seven hundred and twenty-two BSF personnel took part in the trial. They were all males, with an average age of 30.9 ± 7.4 years. All of them were involved in guarding the country's border. They were deputed for 9 days residential training in yoga. Before and after training they were assessed for self-rated sleep, state anxiety and vigilance.

RESULTS: The results suggest the benefits of yoga in BSF personnel. The BSF personnel showed a significant increase in scores in the vigilance test, a decrease in state anxiety, and improved self-rated sleep.}, } @article {pmid30055586, year = {2018}, author = {Wolf, IR and Paschoal, AR and Quiroga, C and Domingues, DS and de Souza, RF and Pretto-Giordano, LG and Vilas-Boas, LA}, title = {Functional annotation and distribution overview of RNA families in 27 Streptococcus agalactiae genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {556}, pmid = {30055586}, issn = {1471-2164}, mesh = {*Genome, Bacterial ; Molecular Sequence Annotation ; RNA, Untranslated/classification/*genetics ; Streptococcus agalactiae/*genetics ; }, abstract = {BACKGROUND: Streptococcus agalactiae, also known as Group B Streptococcus (GBS), is a Gram-positive bacterium that colonizes the gastrointestinal and genitourinary tract of humans. This bacterium has also been isolated from various animals, such as fish and cattle. Non-coding RNAs (ncRNAs) can act as regulators of gene expression in bacteria, such as Streptococcus pneumoniae and Streptococcus pyogenes. However, little is known about the genomic distribution of ncRNAs and RNA families in S. agalactiae.

RESULTS: Comparative genome analysis of 27 S. agalactiae strains showed more than 5 thousand genomic regions identified and classified as Core, Exclusive, and Shared genome sequences. We identified 27 to 89 RNA families per genome distributed over these regions, from these, 25 were in Core regions while Shared and Exclusive regions showed variations amongst strains. We propose that the amount and type of ncRNA present in each genome can provide a pattern to contribute in the identification of the clonal types.

CONCLUSIONS: The identification of RNA families provides an insight over ncRNAs, sRNAs and ribozymes function, that can be further explored as targets for antibiotic development or studied in gene regulation of cellular processes. RNA families could be considered as markers to determine infection capabilities of different strains. Lastly, pan-genome analysis of GBS including the full range of functional transcripts provides a broader approach in the understanding of this pathogen.}, } @article {pmid30055575, year = {2018}, author = {Tríbulo, P and Jumatayeva, G and Lehloenya, K and Moss, JI and Negrón-Pérez, VM and Hansen, PJ}, title = {Effects of sex on response of the bovine preimplantation embryo to insulin-like growth factor 1, activin A, and WNT7A.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {16}, pmid = {30055575}, issn = {1471-213X}, support = {R03 HD080855/HD/NICHD NIH HHS/United States ; R01 HD088352/HD/NICHD NIH HHS/United States ; 2011-67015-30688//National Institute of Food and Agriculture/International ; R01 HD088352//Eunice Kennedy Shriver National Institute of Child Health and Human Development/International ; P30 AI073961/AI/NIAID NIH HHS/United States ; R03 HD080855//Eunice Kennedy Shriver National Institute of Child Health and Human Development/International ; }, abstract = {BACKGROUND: Alterations in maternal environment can sometimes affect embryonic development in a sexually-dimorphic manner. The objective was to determine whether preimplantation bovine embryos respond to three maternally-derived cell signaling molecules in a sex-dependent manner.

RESULTS: Actions of three embryokines known to increase competence of bovine embryos to develop to the blastocyst stage, insulin-like growth factor 1 (IGF1), activin A, and WNT member 7A (WNT7A), were evaluated for actions on embryos produced in vitro with X- or Y- sorted semen from the same bull. Each embryokine was tested in embryos produced by in vitro fertilization of groups of oocytes with either pooled sperm from two bulls or with sperm from individual bulls. Embryos were treated with IGF1, activin A, or WNT7A on day 5 of culture. All three embryokines increased the proportion of cleaved zygotes that developed to the blastocyst stage and the effect was similar for female and male embryos. As an additional test of sexual dimorphism, effects of IGF1 on blastocyst expression of a total of 127 genes were determined by RT-qPCR using the Fluidigm Delta Gene assay. Expression of 18 genes was affected by sex, expression of 4 genes was affected by IGF1 and expression of 3 genes was affected by the IGF1 by sex interaction.

CONCLUSION: Sex did not alter how IGF1, activin A or WNT7A altered developmental competence to the blastocyst stage. Thus, sex-dependent differences in regulation of developmental competence of embryos by maternal regulatory signals is not a general phenomenon. The fact that sex altered how IGF1 regulates gene expression is indicative that there could be sexual dimorphism in embryokine regulation of some aspects of embryonic function other than developmental potential to become a blastocyst.}, } @article {pmid30055574, year = {2018}, author = {Liang, X and Shang, S and Dong, Q and Wang, B and Zhang, R and Gleason, ML and Sun, G}, title = {Transcriptomic analysis reveals candidate genes regulating development and host interactions of Colletotrichum fructicola.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {557}, pmid = {30055574}, issn = {1471-2164}, support = {Z109021712//Chinese Universities Scientific Fund/ ; Z109021610//Chinese Universities Scientific Fund/ ; 31601595//the National Natural Science Foundation of China/ ; 2016M592844//the China Postdoctoral Science Foundation/ ; CARS-28//the China Agriculture Research System/ ; }, mesh = {Cell Wall/metabolism ; Colletotrichum/*genetics/growth & development/metabolism/pathogenicity ; Fungal Proteins/genetics ; Gene Expression Profiling/standards ; *Genes, Fungal ; Oxidative Stress/genetics ; Peptide Hydrolases/genetics/metabolism ; Plant Diseases/microbiology ; Quinic Acid/metabolism ; Secondary Metabolism/genetics ; Sequence Analysis, RNA/standards ; Virulence Factors/genetics ; }, abstract = {BACKGROUND: Colletotrichum is a fungal genus in Ascomycota that contain many plant pathogens. Among all Colletotrichum genomes that have been sequenced, C. fructicola contains the largest number of candidate virulence factors, such as plant cell wall degrading enzymes, secondary metabolite (SM) biosynthetic enzymes, secreted proteinases, and small secreted proteins. Systematic analysis of the expressional patterns of these factors would be an important step toward identifying key virulence determinants.

RESULTS: In this study, we obtained and compared the global transcriptome profiles of four types of infection-related structures: conidia, appressoria, infected apple leaves, and cellophane infectious hyphae (bulbous hyphae spreading inside cellophane) of C. fructicola. We also compared the expression changes of candidate virulence factors among these structures in a systematic manner. A total of 3189 genes were differentially expressed in at least one pairwise comparison. Genes showing in planta-specific expressional upregulations were enriched with small secreted proteins (SSPs), cytochrome P450s, carbohydrate-active enzymes (CAZYs) and secondary metabolite (SM) synthetases, and included homologs of several known candidate effectors and one SM gene cluster specific to the Colletotrichum genus. In conidia, tens of genes functioning in triacylglycerol biosynthesis showed coordinately expressional upregulation, supporting the viewpoint that C. fructicola builds up lipid droplets as energy reserves. Several phosphate starvation responsive genes were coordinately up-regulated during early plant colonization, indicating a phosphate-limited in planta environment immediately faced by biotrophic infectious hyphae.

CONCLUSION: This study systematically analyzes the expression patterns of candidate virulence genes, and reveals biological activities related to the development of several infection-related structures of C. fructicola. Our findings lay a foundation for further dissecting infection mechanisms in Colletotrichum and identifying disease control targets.}, } @article {pmid30055567, year = {2018}, author = {Hou, R and Li, M and Tang, T and Wang, R and Li, Y and Xu, Y and Tang, L and Wang, L and Liu, M and Jiang, Y and Cui, W and Qiao, X}, title = {Construction of Lactobacillus casei ghosts by Holin-mediated inactivation and the potential as a safe and effective vehicle for the delivery of DNA vaccines.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {80}, pmid = {30055567}, issn = {1471-2180}, abstract = {BACKGROUND: Bacterial ghosts (BGs) are empty bacterial cell envelopes generated by releasing the cellular contents. In this study, a phage infecting Lactobacillus casei ATCC 393 (L. casei 393) was isolated and designated Lcb. We aimed at using L. casei 393 as an antigen delivery system to express phage-derived holin for development of BGs.

RESULTS: A gene fragment encoding holin of Lcb (hocb) was amplified by polymerase chain reaction (PCR). We used L. casei 393 as an antigen delivery system to construct the recombinant strain pPG-2-hocb/L. casei 393. Then the recombinants were induced to express hocb. The immunoreactive band corresponding to hocb was observed by western-blotting, demonstrating the efficiency and specificity of hocb expression in recombinants. The measurements of optical density at 600 nm (OD600) after induction showed that expression of hocb can be used to convert L. casei cells into BGs. TEM showed that the cytomembrane and cell walls of hocb expressing cells were partially disrupted, accompanied by the loss of cellular contents, whereas control cells did not show any morphological changes. SEM showed that lysis pores were distributed in the middle or at the poles of the cells. To examine where the plasmid DNA was associated, we analyzed the L. casei ghosts loading SYBR Green I labeled pCI-EGFP by confocal microscopy. The result demonstrated that the DNA interacted with the inside rather than with the outside surface of the BGs. To further analyze where the DNA were loaded, we stained BGs with MitoTracker Green FM and the loaded plasmids were detected using EGFP-specific Cy-3-labeled probes. Z-scan sections through the BGs revealed that pCI-EGFP (red) was located within the BGs (green), but not on the outside. Flow cytometry and qPCR showed that the DNA was loaded onto BGs effectively and stably.

CONCLUSIONS: Our study constructed L. casei BGs by a novel method, which may be a promising technology for promoting the further application of DNA vaccine, providing experimental data to aid the development of other Gram-positive BGs.}, } @article {pmid30055354, year = {2018}, author = {Linard, B and Crampton-Platt, A and Moriniere, J and Timmermans, MJTN and Andújar, C and Arribas, P and Miller, KE and Lipecki, J and Favreau, E and Hunter, A and Gómez-Rodríguez, C and Barton, C and Nie, R and Gillett, CPDT and Breeschoten, T and Bocak, L and Vogler, AP}, title = {The contribution of mitochondrial metagenomics to large-scale data mining and phylogenetic analysis of Coleoptera.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {1-11}, doi = {10.1016/j.ympev.2018.07.008}, pmid = {30055354}, issn = {1095-9513}, abstract = {A phylogenetic tree at the species level is still far off for highly diverse insect orders, including the Coleoptera, but the taxonomic breadth of public sequence databases is growing. In addition, new types of data may contribute to increasing taxon coverage, such as metagenomic shotgun sequencing for assembly of mitogenomes from bulk specimen samples. The current study explores the application of these techniques for large-scale efforts to build the tree of Coleoptera. We used shotgun data from 17 different ecological and taxonomic datasets (5 unpublished) to assemble a total of 1942 mitogenome contigs of >3000 bp. These sequences were combined into a single dataset together with all mitochondrial data available at GenBank, in addition to nuclear markers widely used in molecular phylogenetics. The resulting matrix of nearly 16,000 species with two or more loci produced trees (RAxML) showing overall congruence with the Linnaean taxonomy at hierarchical levels from suborders to genera. We tested the role of full-length mitogenomes in stabilizing the tree from GenBank data, as mitogenomes might link terminals with non-overlapping gene representation. However, the mitogenome data were only partly useful in this respect, presumably because of the purely automated approach to assembly and gene delimitation, but improvements in future may be possible by using multiple assemblers and manual curation. In conclusion, the combination of data mining and metagenomic sequencing of bulk samples provided the largest phylogenetic tree of Coleoptera to date, which represents a summary of existing phylogenetic knowledge and a defensible tree of great utility, in particular for studies at the intra-familial level, despite some shortcomings for resolving basal nodes.}, } @article {pmid30055069, year = {2018}, author = {Gygax, M and Rentsch, AK and Rudman, SM and Rennison, DJ}, title = {Differential predation alters pigmentation in threespine stickleback (Gasterosteus aculeatus).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1589-1598}, doi = {10.1111/jeb.13354}, pmid = {30055069}, issn = {1420-9101}, support = {//National Science and Engineering Research Council of Canada Discovery (NSERC)/ ; //University of British Columbia Four Year Fellowships/ ; }, abstract = {Animal pigmentation plays a key role in many biological interactions, including courtship and predator avoidance. Sympatric benthic and limnetic ecotypes of threespine stickleback (Gasterosteus aculeatus) exhibit divergent pigment patterns. To test whether differential predation by cutthroat trout contributes to the differences in pigmentation seen between the ecotypes, we used a within-generation selection experiment on F2 benthic-limnetic hybrids. After 10 months of differential selection, we compared the pigmentation of fish under trout predation to control fish not exposed to trout predation. We found that stickleback exhibited more lateral barring in ponds with trout predation. Ponds with trout were also less turbid, and a greater degree of barring was negatively correlated with the magnitude of turbidity across pond replicates. A more benthic diet, a proxy for habitat use, was also correlated with greater lateral barring and green dorsal pigmentation. These patterns suggest that differential exposure to cutthroat trout predation may explain the divergence in body pigmentation between benthic and limnetic ecotypes.}, } @article {pmid30055064, year = {2018}, author = {Matsumura, K and Miyatake, T}, title = {Costs of walking: differences in egg size and starvation resistance of females between strains of the red flour beetle (Tribolium castaneum) artificially selected for walking ability.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {11}, pages = {1632-1637}, doi = {10.1111/jeb.13356}, pmid = {30055064}, issn = {1420-9101}, support = {16J0445818//Japan Society for the Promotion of Science/ ; 26291091//Japan Society for the Promotion of Science/ ; 17H05976//Japan Society for the Promotion of Science/ ; 18H02510//Japan Society for the Promotion of Science/ ; //MEXT/ ; }, abstract = {In many animals, movement often affects fitness components such as foraging or migration. On the other hand, individuals with higher mobility also often have fitness costs. This trade-off between movement and other traits may explain the maintenance of variation in moving ability in a population. However, few studies have focused on movement by walking, although many previous studies of insects have investigated the evolution of variations in mobility with wing polymorphism. In this study, we focused on the walking ability of the red flour beetle (Tribolium castaneum) and investigated whether females with higher than lower walking ability have fitness costs. The present results showed that females with genetically higher walking ability produced smaller eggs and had lower starvation resistance than females with lower walking ability. These results suggest that higher walking ability is costly for females, and this fitness cost may explain maintenance of variations of walking ability in a population.}, } @article {pmid30055021, year = {2018}, author = {Kemp, DJ and Batistic, FK and Reznick, DN}, title = {Predictable adaptive trajectories of sexual coloration in the wild: Evidence from replicate experimental guppy populations.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {11}, pages = {2462-2477}, doi = {10.1111/evo.13564}, pmid = {30055021}, issn = {1558-5646}, support = {DEB 1258231//National Science Foundation/ ; DEB 1556884//National Science Foundation/ ; EF 0623632//National Science Foundation/ ; DP160103668//Australian Research Council/ ; ATR00350//Natural Environment Research Council/ ; }, abstract = {The question of whether populations evolve predictably and consistently under similar selective regimes is fundamental to understanding how adaptation proceeds in the wild. We address this question with a replicated evolution experiment focused upon male sexual coloration in guppies (Poecilia reticulata). Fish were transplanted from a single high predation population in the Guanapo River to four replicate, guppy-free low predation headwater streams. Two streams had their canopies thinned to adjust the setting under which male coloration is displayed and perceived. We assessed evolutionary divergence using second-generation lab-bred offspring of fish sampled four to six years following translocation. A prior experiment of the same design, performed in an adjacent drainage, resulted in the evolution of more extensive orange, black, and iridescent markings. We however found evidence for expansion only in structural coloration (iridescent blue/green), no change in orange, and a reduction in black. This response amplifies earlier findings for Guanapo fish, revealing that trajectories of color elaboration differ among drainages. We also found that color phenotypes evolved more greatly at the thinned-canopy sites. Our findings support the predictability of sexual trait evolution in the wild, and underscore the importance of signaling conditions and ornamental starting points in shaping adaptive trajectories.}, } @article {pmid30055007, year = {2018}, author = {Herrera-Alsina, L and Pigot, AL and Hildenbrandt, H and Etienne, RS}, title = {The influence of ecological and geographic limits on the evolution of species distributions and diversity.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {1978-1991}, pmid = {30055007}, issn = {1558-5646}, abstract = {The role of ecological limits in regulating the distribution and diversification of species remains controversial. Although such limits must ultimately arise from constraints on local species coexistence, this spatial context is missing from most macroevolutionary models. Here, we develop a stochastic, spatially explicit model of species diversification to explore the phylogenetic and biogeographic patterns expected when local diversity is bounded. We show how local ecological limits, by regulating opportunities for range expansion and thus rates of speciation and extinction, lead to temporal slowdowns in diversification and predictable differences in equilibrium diversity between regions. However, our models also show that even when regions have identical diversity limits, the dynamics of diversification and total number of species supported at equilibrium can vary dramatically depending on the relative size of geographic and local ecological niche space. Our model predicts that small regions with higher local ecological limits support a higher standing diversity and more balanced phylogenetic trees than large geographic areas with more stringent constraints on local coexistence. Our findings highlight how considering the spatial context of diversification can provide new insights into the role of ecological limits in driving variation in biodiversity across space, time, and clades.}, } @article {pmid30054599, year = {2018}, author = {}, title = {One code.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1061}, doi = {10.1038/s41588-018-0194-9}, pmid = {30054599}, issn = {1546-1718}, } @article {pmid30054598, year = {2018}, author = {Thomsen, SK and Raimondo, A and Hastoy, B and Sengupta, S and Dai, XQ and Bautista, A and Censin, J and Payne, AJ and Umapathysivam, MM and Spigelman, AF and Barrett, A and Groves, CJ and Beer, NL and Manning Fox, JE and McCarthy, MI and Clark, A and Mahajan, A and Rorsman, P and MacDonald, PE and Gloyn, AL}, title = {Type 2 diabetes risk alleles in PAM impact insulin release from human pancreatic β-cells.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1122-1131}, pmid = {30054598}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; U01 DK085545/DK/NIDDK NIH HHS/United States ; U01 DK105535/DK/NIDDK NIH HHS/United States ; }, abstract = {The molecular mechanisms underpinning susceptibility loci for type 2 diabetes (T2D) remain poorly understood. Coding variants in peptidylglycine α-amidating monooxygenase (PAM) are associated with both T2D risk and insulinogenic index. Here, we demonstrate that the T2D risk alleles impact negatively on overall PAM activity via defects in expression and catalytic function. PAM deficiency results in reduced insulin content and altered dynamics of insulin secretion in a human β-cell model and primary islets from cadaveric donors. Thus, our results demonstrate a role for PAM in β-cell function, and establish molecular mechanisms for T2D risk alleles at this locus.}, } @article {pmid30054597, year = {2018}, author = {Seoighe, C and Tosh, NJ and Greally, JM}, title = {DNA methylation haplotypes as cancer markers.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1062-1063}, doi = {10.1038/s41588-018-0185-x}, pmid = {30054597}, issn = {1546-1718}, } @article {pmid30054596, year = {2018}, author = {Diep, D and Zhang, K}, title = {Reply to 'DNA methylation haplotypes as cancer markers'.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1063-1066}, doi = {10.1038/s41588-018-0186-9}, pmid = {30054596}, issn = {1546-1718}, } @article {pmid30054595, year = {2018}, author = {Richardson, CD and Kazane, KR and Feng, SJ and Zelin, E and Bray, NL and Schäfer, AJ and Floor, SN and Corn, JE}, title = {CRISPR-Cas9 genome editing in human cells occurs via the Fanconi anemia pathway.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1132-1139}, doi = {10.1038/s41588-018-0174-0}, pmid = {30054595}, issn = {1546-1718}, abstract = {CRISPR-Cas genome editing creates targeted DNA double-strand breaks (DSBs) that are processed by cellular repair pathways, including the incorporation of exogenous DNA via single-strand template repair (SSTR). To determine the genetic basis of SSTR in human cells, we developed a coupled inhibition-cutting system capable of interrogating multiple editing outcomes in the context of thousands of individual gene knockdowns. We found that human Cas9-induced SSTR requires the Fanconi anemia (FA) pathway, which is normally implicated in interstrand cross-link repair. The FA pathway does not directly impact error-prone, non-homologous end joining, but instead diverts repair toward SSTR. Furthermore, FANCD2 protein localizes to Cas9-induced DSBs, indicating a direct role in regulating genome editing. Since FA is itself a genetic disease, these data imply that patient genotype and/or transcriptome may impact the effectiveness of gene editing treatments and that treatments biased toward FA repair pathways could have therapeutic value.}, } @article {pmid30054594, year = {2018}, author = {MacGregor, S and Ong, JS and An, J and Han, X and Zhou, T and Siggs, OM and Law, MH and Souzeau, E and Sharma, S and Lynn, DJ and Beesley, J and Sheldrick, B and Mills, RA and Landers, J and Ruddle, JB and Graham, SL and Healey, PR and White, AJR and Casson, RJ and Best, S and Grigg, JR and Goldberg, I and Powell, JE and Whiteman, DC and Radford-Smith, GL and Martin, NG and Montgomery, GW and Burdon, KP and Mackey, DA and Gharahkhani, P and Craig, JE and Hewitt, AW}, title = {Genome-wide association study of intraocular pressure uncovers new pathways to glaucoma.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1067-1071}, doi = {10.1038/s41588-018-0176-y}, pmid = {30054594}, issn = {1546-1718}, abstract = {Intraocular pressure (IOP) is currently the sole modifiable risk factor for primary open-angle glaucoma (POAG), one of the leading causes of blindness worldwide1. Both IOP and POAG are highly heritable2. We report a combined analysis of participants from the UK Biobank (n = 103,914) and previously published data from the International Glaucoma Genetic Consortium (n = 29,578)3,4 that identified 101 statistically independent genome-wide-significant SNPs for IOP, 85 of which have not been previously reported4-12. We examined these SNPs in 11,018 glaucoma cases and 126,069 controls, and 53 SNPs showed evidence of association. Gene-based tests implicated an additional 22 independent genes associated with IOP. We derived an allele score based on the IOP loci and loci influencing optic nerve head morphology. In 1,734 people with advanced glaucoma and 2,938 controls, participants in the top decile of the allele score were at increased risk (odds ratio (OR) = 5.6; 95% confidence interval (CI): 4.1-7.6) of glaucoma relative to the bottom decile.}, } @article {pmid30054568, year = {2018}, author = {Strobel, EJ and Yu, AM and Lucks, JB}, title = {High-throughput determination of RNA structures.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {615-634}, doi = {10.1038/s41576-018-0034-x}, pmid = {30054568}, issn = {1471-0064}, support = {DP2 GM110838/GM/NIGMS NIH HHS/United States ; T32 GM083937/GM/NIGMS NIH HHS/United States ; }, abstract = {RNA performs and regulates a diverse range of cellular processes, with new functional roles being uncovered at a rapid pace. Interest is growing in how these functions are linked to RNA structures that form in the complex cellular environment. A growing suite of technologies that use advances in RNA structural probes, high-throughput sequencing and new computational approaches to interrogate RNA structure at unprecedented throughput are beginning to provide insights into RNA structures at new spatial, temporal and cellular scales.}, } @article {pmid30054567, year = {2018}, author = {Dart, A}, title = {How to predict the future.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {531}, doi = {10.1038/s41576-018-0041-y}, pmid = {30054567}, issn = {1471-0064}, } @article {pmid30054316, year = {2018}, author = {Fournié, G and Waret-Szkuta, A and Camacho, A and Yigezu, LM and Pfeiffer, DU and Roger, F}, title = {A dynamic model of transmission and elimination of peste des petits ruminants in Ethiopia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8454-8459}, pmid = {30054316}, issn = {1091-6490}, mesh = {Animals ; Ethiopia/epidemiology ; Goats ; Peste-des-Petits-Ruminants/immunology/prevention & control/*transmission ; Sheep ; Vaccination ; }, abstract = {Peste des petits ruminants (PPR), a devastating viral disease of sheep and goats, has been targeted by the global community for eradication within the next 15 years. Although an efficacious attenuated live vaccine is available, the lack of knowledge about the transmission potential of PPR virus (PPRV) may compromise eradication efforts. By fitting a metapopulation model simulating PPRV spread to the results of a nationwide serological survey in Ethiopia, we estimated the level of viral transmission in an endemic setting and the vaccination coverage required for elimination. Results suggest that the pastoral production system as a whole acts as a viral reservoir, from which PPRV spills over into the sedentary production system, where viral persistence is uncertain. Estimated levels of PPRV transmission indicate that viral spread could be prevented if the proportion of immune small ruminants is kept permanently above 37% in at least 71% of pastoral village populations. However, due to the high turnover of these populations, maintaining the fraction of immune animals above this threshold would require high vaccine coverage within villages, and vaccination campaigns to be conducted annually. Adapting vaccination strategies to the specific characteristics of the local epidemiological context and small ruminant population dynamics would result in optimized allocation of limited resources and increase the likelihood of PPR eradication.}, } @article {pmid30054315, year = {2018}, author = {Mei, S and Montanari, A and Nguyen, PM}, title = {A mean field view of the landscape of two-layer neural networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7665-E7671}, doi = {10.1073/pnas.1806579115}, pmid = {30054315}, issn = {1091-6490}, abstract = {Multilayer neural networks are among the most powerful models in machine learning, yet the fundamental reasons for this success defy mathematical understanding. Learning a neural network requires optimizing a nonconvex high-dimensional objective (risk function), a problem that is usually attacked using stochastic gradient descent (SGD). Does SGD converge to a global optimum of the risk or only to a local optimum? In the former case, does this happen because local minima are absent or because SGD somehow avoids them? In the latter, why do local minima reached by SGD have good generalization properties? In this paper, we consider a simple case, namely two-layer neural networks, and prove that-in a suitable scaling limit-SGD dynamics is captured by a certain nonlinear partial differential equation (PDE) that we call distributional dynamics (DD). We then consider several specific examples and show how DD can be used to prove convergence of SGD to networks with nearly ideal generalization error. This description allows for "averaging out" some of the complexities of the landscape of neural networks and can be used to prove a general convergence result for noisy SGD.}, } @article {pmid30053907, year = {2018}, author = {Cheng, C and Wickham, JD and Chen, L and Xu, D and Lu, M and Sun, J}, title = {Bacterial microbiota protect an invasive bark beetle from a pine defensive compound.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {132}, pmid = {30053907}, issn = {2049-2618}, mesh = {Animals ; Bacterial Proteins/genetics ; Coleoptera/*growth & development/microbiology ; Flavanones/*metabolism ; Fungal Proteins/genetics ; Gene Regulatory Networks ; Gram-Negative Bacteria/classification/isolation & purification/*physiology ; Microbiota ; Phylogeny ; Pinus/*chemistry/parasitology ; Proteolysis ; Saccharomycetales/physiology ; Symbiosis ; }, abstract = {BACKGROUND: There is growing evidence that some devastating biotic invasions are facilitated by microbial symbionts. The red turpentine beetle (RTB), an innocuous secondary insect attacking weakened trees in North America, has formed an invasive complex with the fungus Leptographium procerum in China, and this invasive beetle-fungus symbiotic complex is capable of attacking and killing healthy pines. A previous study demonstrated that three Chinese-resident fungi, newly acquired by RTB in China, induce high levels of a phenolic defensive chemical, naringenin, in pines and this invasive beetle-fungus complex is suppressed by elevated levels of naringenin while the beetle uses its gallery as an external detoxification system in which particular yeast-like fungi and bacterial species biodegrade naringenin. However, the functional roles of key microbial players in the symbiosis, contained within the microbiome of the bark beetle gallery, have not been well elucidated.

RESULTS: In this report, the symbiotic naringenin-degrading microbiota were found to increase RTB survivorship in the presence of induced host defenses, and potential genes associated with degradation pathways were discovered. While fungi in the gallery microbiota had little involvement in naringenin degradation, bacterial community structure within the beetle gallery was highly correlated to naringenin degrading activity. Phylotypes of the Gram-negative bacterial genus Novosphingobium, which possessed genes involved in degradation pathways, were highly correlated to naringenin degradation activities and RTB associated with an isolated species of this genus acquired protection against naringenin and gained fitness.

CONCLUSIONS: Our results demonstrated that symbiotic bacterial community of RTB galleries enhances the survivorship and overall fitness of invasive beetles by degrading the host phenolic naringenin, ultimately overcoming the tree defenses and facilitating the success of the invasive beetle-fungi complex. This dynamic interplay between the invasive insect pest and multipartite microbes suggests a putative mechanism in invasion ecology for mitigating biotic resistance to symbiotic invasion.}, } @article {pmid30053887, year = {2018}, author = {Frøysa, HG and Fallahi, S and Blaser, N}, title = {Evaluating model reduction under parameter uncertainty.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {79}, pmid = {30053887}, issn = {1752-0509}, support = {248840//Norges Forskningsråd/ ; }, abstract = {BACKGROUND: The dynamics of biochemical networks can be modelled by systems of ordinary differential equations. However, these networks are typically large and contain many parameters. Therefore model reduction procedures, such as lumping, sensitivity analysis and time-scale separation, are used to simplify models. Although there are many different model reduction procedures, the evaluation of reduced models is difficult and depends on the parameter values of the full model. There is a lack of a criteria for evaluating reduced models when the model parameters are uncertain.

RESULTS: We developed a method to compare reduced models and select the model that results in similar dynamics and uncertainty as the original model. We simulated different parameter sets from the assumed parameter distributions. Then, we compared all reduced models for all parameter sets using cluster analysis. The clusters revealed which of the reduced models that were similar to the original model in dynamics and variability. This allowed us to select the smallest reduced model that best approximated the full model. Through examples we showed that when parameter uncertainty was large, the model should be reduced further and when parameter uncertainty was small, models should not be reduced much.

CONCLUSIONS: A method to compare different models under parameter uncertainty is developed. It can be applied to any model reduction method. We also showed that the amount of parameter uncertainty influences the choice of reduced models.}, } @article {pmid30053880, year = {2018}, author = {Musuka, G and Mutenherwa, F and Mukandavire, Z and Chingombe, I and Mapingure, M}, title = {Association between alcohol use and HIV status: findings from Zambia and Zimbabwe.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {508}, pmid = {30053880}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Alcohol Drinking/*epidemiology ; Female ; HIV Infections/*epidemiology ; Health Surveys ; Humans ; Male ; Middle Aged ; Prevalence ; Young Adult ; Zambia/epidemiology ; Zimbabwe/epidemiology ; }, abstract = {OBJECTIVE: To conduct statistical analysis to assess the association between alcohol use and HIV status using Demographic Health Survey data from Zambia (2013-2014) and Zimbabwe (2015-2016).

RESULTS: The study showed an association between alcohol use and HIV status using nationally representative population-based surveys. The surveys were conducted among men (15-54 years) and women (15-49 years) in 2013-2014 and 2015-2016 in Zambia and Zimbabwe respectively. HIV prevalence in the two countries was higher among males and females who drank alcohol compared to those who did not. This study reinforces the existing knowledge base on the association between alcohol use and HIV sero-status and calls for further research to explore the causal pathways between alcohol consumption and HIV status.}, } @article {pmid30053877, year = {2018}, author = {Canizo, JR and Vazquez Echegaray, C and Klisch, D and Aller, JF and Paz, DA and Alberio, RH and Alberio, R and Guberman, AS}, title = {Exogenous human OKSM factors maintain pluripotency gene expression of bovine and porcine iPS-like cells obtained with STEMCCA delivery system.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {509}, pmid = {30053877}, issn = {1756-0500}, support = {PICT Raíces No 1727-2013//FONCYT-ANPCYT/ ; }, mesh = {Animals ; Cattle ; *Cell Differentiation ; Cellular Reprogramming ; Fibroblasts ; Gene Expression Regulation ; Humans ; *Induced Pluripotent Stem Cells ; Kruppel-Like Transcription Factors/metabolism ; Lentivirus ; Octamer Transcription Factor-3/*physiology ; SOXB1 Transcription Factors/metabolism ; Swine ; }, abstract = {OBJECTIVES: The use of induced pluripotent stem (iPS) cells as an alternative to embryonic stem cells to produce transgenic animals requires the development of a biotechnological platform for their generation. In this study, different strategies for the generation of bovine and porcine iPS cells were evaluated. Lentiviral vectors were used to deliver human factors OCT4, SOX2, KLF4 and c-MYC (OKSM) into bovine and porcine embryonic fibroblasts and different culture conditions were evaluated.

RESULTS: Protocols based on the integrative lentiviral vector STEMCCA produced porcine iPS-like cells more efficiently than in bovine cells. The iPS-like cells generated displayed stem cell features; however, expression of exogenous factors was maintained along at least 12 passages. Since inactivation of the exogenous factors is still a major bottleneck for establishing fully reprogrammed iPS cells, defining culture conditions that support endogenous OKSM expression is critical for the efficient generation of farm animals' iPS cells.}, } @article {pmid30053830, year = {2018}, author = {Berehe, TT and Bekele, GE and Yimer, YS and Lozza, TZ}, title = {Assessment of clients satisfaction with outpatient services at Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {507}, pmid = {30053830}, issn = {1756-0500}, support = {4//Yekatit 12 Hospital Medical college/ ; }, mesh = {Adult ; Ambulatory Care/*standards ; Cross-Sectional Studies ; Ethiopia ; Female ; Humans ; Male ; Middle Aged ; *Patient Satisfaction ; Reproducibility of Results ; }, abstract = {OBJECTIVE: This study aimed at assessing clients' satisfaction and associated factors among adults. A cross sectional facility based study was conducted on 420 clients of Yekatit 12 Hospital Medical College from 1 June 2016 to 1 July 2016. Data was entered, cleaned, and analyzed using SPSS statistical package. Data was analyzed using a multivariable logistic regression model to find out the most significant predictors for clients satisfaction with outpatient services at Yekatit 12 Hospital Medical College.

RESULTS: This study showed that the overall clients' satisfaction level towards out-patient health service at Yekatit 12 Hospital Medical College was 47% at 95% CI (42.5, 51.7%). The most frequently identified problems were: lack of clean toilet in nearby the waiting areas, lack of waiting area particularly at pharmacy, inadequate furniture like chair, lack of adequate drugs and supplies, lack of privacy at the examination room, lack of direction signs, and poor communication between clients and health service providers. In conclusion the overall satisfaction level of the patients is low, so this demands the Hospital to take further action on the identified problems to improve the services delivered to the patients.}, } @article {pmid30053829, year = {2018}, author = {Isaranuwatchai, W and Bayoumi, AM and Renahy, E and Cheff, R and O'Campo, P}, title = {Using decision methods to examine the potential impact of intersectoral action programs.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {506}, pmid = {30053829}, issn = {1756-0500}, mesh = {Budgets ; Cost-Benefit Analysis ; *Decision Support Techniques ; *Public Health ; }, abstract = {OBJECTIVES: In public health today, there is a widespread call for intersectoral action (ISA) programs, in which two or more sectors cooperate to address a problem. This trend raises a question of how to appropriately assess the effectiveness and cost-effectiveness of ISA programs. To assess the impact of ISA, evaluation methods should provide a framework for simultaneously considering the impact of two or more interventions when selecting from a portfolio of programs. There is a gap in literature on such methods. In this research note, from a narrative review, we report and describe methods that could be useful for evaluating ISA programs. Subsequently, we present a hypothetical case study to demonstrate the use of these methods.

RESULTS: We identified four methods that have potential to assess the joint impact of multiple interventions: economic evaluation, portfolio analysis, multiple-criteria decision analysis, and programme budgeting and marginal analysis. To keep pace with the desire to use strong evidence to inform the selection and design of ISA programs, methods must evolve to support these initiatives. This research note seeks to begin a dialogue on existing decision methods which may be used to assist decision makers with funding and resource allocation decisions of ISA programs.}, } @article {pmid30053828, year = {2018}, author = {Haste, A and Penn, L and Rodrigues, AM and Marques, MM and Budig, K and Bell, R and Summerbell, C and White, M and Adamson, AJ and Sniehotta, FF}, title = {Using evidence-based guidelines to inform service provision: a structured mapping exercise within the National Health Service Diabetes Prevention Programme in England.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {510}, pmid = {30053828}, issn = {1756-0500}, support = {MR/K023187/1//Medical Research Council/United Kingdom ; }, mesh = {Diabetes Mellitus/*prevention & control ; England ; *Exercise ; Humans ; *National Health Programs ; }, abstract = {OBJECTIVE: The National Health Service (NHS) in England planned a national diabetes prevention programme (NHS DPP) with phased implementation. Evidence-based guidelines and service specifications support efficient and effective translation of research into practice. We aimed to evaluate the use of a structured mapping exercise to appraise how evidence, service specification and early phase practice could inform recommendations to guide subsequent implementation of the NHS DPP.

RESULTS: The mapping exercise facilitated comparison and appraisal of key components from different documentary sources (evidence-based NICE guidelines, service specification, and provider documents). Key components were categorised into (A) pathways into programmes, (B) intervention content (C) inequalities and (D) quality assurance and staff training. We identified where key components were the same (accordance), where they varied (discrepancies) and where they were lacking (discontinuities), across the documentary sources. For example there was discrepancy in intervention duration and discontinuity in intervention enrolment procedures. This mapping exercise was useful to compare the fidelity in translation of evidence-based guidance into service specification and programme documents, thus identifying where future service implementation might be improved. This method may be applicable for use with other health conditions where research evidence requires translation into real world population programmes.}, } @article {pmid30053802, year = {2018}, author = {Lin, Z and Damaris, RN and Shi, T and Li, J and Yang, P}, title = {Transcriptomic analysis identifies the key genes involved in stamen petaloid in lotus (Nelumbo nucifera).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {554}, pmid = {30053802}, issn = {1471-2164}, support = {No. 31700197//National Natural Science Foundation of China/ ; }, mesh = {Flowers/anatomy & histology/*genetics/metabolism ; Gene Expression Profiling ; *Genes, Plant ; Nelumbo/anatomy & histology/*genetics/metabolism ; Phenotype ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: Flower morphology, a phenomenon regulated by a complex network, is one of the vital ornamental features in Nelumbo nucifera. Stamen petaloid is very prevalent in lotus flowers. However, the mechanism underlying this phenomenon is still obscure.

RESULTS: Here, the comparative transcriptomic analysis was performed among petal, stamen petaloid and stamen through RNA-seq. Using pairwise comparison analysis, a large number of genes involved in hormonal signal transduction pathways and transcription factors, especially the MADS-box genes, were identified as candidate genes for stamen petaloid in lotus.

CONCLUSIONS: Taken together, these results provide an insight into the molecular networks underlying lotus floral organ development and stamen petaloid.}, } @article {pmid30053801, year = {2018}, author = {Bose, T and Das, C and Dutta, A and Mahamkali, V and Sadhu, S and Mande, SS}, title = {Understanding the role of interactions between host and Mycobacterium tuberculosis under hypoxic condition: an in silico approach.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {555}, pmid = {30053801}, issn = {1471-2164}, support = {BT/PR3260/BRB/10/967/2011//Department of Biotechnology , Ministry of Science and Technology/ ; }, mesh = {Bacterial Proteins/metabolism ; Cell Hypoxia ; Computer Simulation ; Gene Regulatory Networks ; *Host-Pathogen Interactions ; Humans ; Macrophages/metabolism/microbiology ; Mycobacterium tuberculosis/*genetics/*metabolism ; Protein Interaction Mapping ; }, abstract = {BACKGROUND: Mycobacterium tuberculosis infection in humans is often associated with extended period of latency. To adapt to the hostile hypoxic environment inside a macrophage, M. tuberculosis cells undergo several physiological and metabolic changes. Previous studies have mostly focused on inspecting individual facets of this complex process. In order to gain deeper insights into the infection process and to understand the coordination among different regulatory/ metabolic pathways in the pathogen, the current in silico study investigates three aspects, namely, (i) host-pathogen interactions (HPIs) between human and M. tuberculosis proteins, (ii) gene regulatory network pertaining to adaptation of M. tuberculosis to hypoxia and (iii) alterations in M. tuberculosis metabolism under hypoxic condition. Subsequently, cross-talks between these components have been probed to evaluate possible gene-regulatory events as well as HPIs which are likely to drive metabolic changes during pathogen's adaptation to the intra-host hypoxic environment.

RESULTS: The newly identified HPIs suggest the pathogen's ability to subvert host mediated reactive oxygen intermediates/ reactive nitrogen intermediates (ROI/ RNI) stress as well as their potential role in modulating host cell cycle and cytoskeleton structure. The results also indicate a significantly pronounced effect of HPIs on hypoxic metabolism of M. tuberculosis. Findings from the current study underscore the necessity of investigating the infection process from a systems-level perspective incorporating different facets of intra-cellular survival of the pathogen.

CONCLUSIONS: The comprehensive host-pathogen interaction network, a Boolean model of M. tuberculosis H37Rv (Mtb) hypoxic gene-regulation, as well as a genome scale metabolic model of Mtb, built for this study are expected to be useful resources for future studies on tuberculosis infection.}, } @article {pmid30053800, year = {2018}, author = {Brzek, A and Cichocka, M and Dolata, J and Juzwa, W and Schümperli, D and Raczynska, KD}, title = {Positive cofactor 4 (PC4) contributes to the regulation of replication-dependent canonical histone gene expression.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {9}, pmid = {30053800}, issn = {1471-2199}, support = {UMO-2013/11/N/NZ1/00010//Narodowe Centrum Nauki/International ; UMO-2012/05/B/NZ2/00826//Narodowe Centrum Nauki/International ; UMO-2015/19/B/NZ1/00233//Narodowe Centrum Nauki/International ; FNP START 2016//Fundacja na rzecz Nauki Polskiej/International ; }, mesh = {Cell Cycle ; Cleavage Stimulation Factor/metabolism ; *DNA Replication ; DNA-Binding Proteins/*metabolism ; Gene Expression Regulation ; HEK293 Cells ; HeLa Cells ; Histones/*genetics ; Humans ; RNA 3' End Processing ; RNA Polymerase II/*metabolism ; Ribonucleoprotein, U7 Small Nuclear/metabolism ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Core canonical histones are required in the S phase of the cell cycle to pack newly synthetized DNA, therefore the expression of their genes is highly activated during DNA replication. In mammalian cells, this increment is achieved by both enhanced transcription and 3' end processing. In this paper, we described positive cofactor 4 (PC4) as a protein that contributes to the regulation of replication-dependent histone gene expression.

RESULTS: We showed that PC4 influences RNA polymerase II recruitment to histone gene loci in a cell cycle-dependent manner. The most important effect was observed in S phase where PC4 knockdown leads to the elevated level of RNA polymerase II on histone genes, which corresponds to the increased total level of those gene transcripts. The opposite effect was caused by PC4 overexpression. Moreover, we found that PC4 has a negative effect on the unique 3' end processing of histone pre-mRNAs that can be based on the interaction of PC4 with U7 snRNP and CstF64. Interestingly, this effect does not depend on the cell cycle.

CONCLUSIONS: We conclude that PC4 might repress RNA polymerase II recruitment and transcription of replication-dependent histone genes in order to maintain the very delicate balance between histone gene expression and DNA synthesis. It guards the cell from excess of histones in S phase. Moreover, PC4 might promote the interaction of cleavage and polyadenylation complex with histone pre-mRNAs, that might impede with the recruitment of histone cleavage complex. This in turn decreases the 3' end processing efficiency of histone gene transcripts.}, } @article {pmid30053798, year = {2018}, author = {Yi, BR and Kim, HJ and Park, HS and Cho, YJ and Kim, JY and Yee, J and Chung, JE and Kim, JH and Lee, KE and Gwak, HS}, title = {Association between MKRN3 and LIN28B polymorphisms and precocious puberty.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {47}, pmid = {30053798}, issn = {1471-2156}, support = {2010-0026225//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: The present study aimed to investigate the association between MKRN3 and LIN28B gene polymorphisms and precocious puberty in Korean boys and girls.

RESULTS: Children 7 to 9 years of age in 2011 to 2012 who were part of the Ewha Birth & Growth Cohort Study were recruited for this study. A total of 103 girls and 70 boys were included in the analyses. Seven girls and 26 boys were identified to have precocious puberty. Among four single nucleotide polymorphisms (SNPs) of MKRN3 and two SNPs of LIN28B examined, three SNPs (rs2239669, rs6576457, and rs12441827) showed significant associations with precocious puberty in additive models in boys but no significance was found in any SNPs in girls. From the logistic regression analysis, boys with TT alleles in rs12441827 had about a four-times greater risk for precocious puberty when compared to C allele carriers (OR = 3.95, 95% CI = 1.27-12.32 in model 1). eQTL analysis revealed that SNPs of statistical significance from our study did not show the variation in expression profiles nor found in the database.

CONCLUSIONS: This study supports the impact of MKRN3 SNP rs12441827 on precocious puberty in Korean boys. The results add a further aspect to genetic association in precocious puberty along with complex interactions of environmental, nutritional and socioeconomic factors.}, } @article {pmid30053797, year = {2018}, author = {Espada, M and Eves-van den Akker, S and Maier, T and Vijayapalani, P and Baum, T and Mota, M and Jones, JT}, title = {STATAWAARS: a promoter motif associated with spatial expression in the major effector-producing tissues of the plant-parasitic nematode Bursaphelenchus xylophilus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {553}, pmid = {30053797}, issn = {1471-2164}, support = {SFRH/BD/84541/2012//FCT - Foundation for Science and Technology/ ; UID/AGR/00115/2013//FCT - Foundation for Science and Technology/ ; BB/M014207/1//Biotechnology and Biological Sciences Research Council (GB)/ ; }, mesh = {Animals ; Nucleotide Motifs ; Pharynx/metabolism ; *Promoter Regions, Genetic ; Transcriptome ; Tylenchida/*genetics/metabolism ; }, abstract = {BACKGROUND: Plant-parasitic nematodes cause severe damage to a wide range of crop and forest species worldwide. The migratory endoparasitic nematode, Bursaphelenchus xylophilus, (pinewood nematode) is a quarantine pathogen that infects pine trees and has a hugely detrimental economic impact on the forestry industry. Under certain environmental conditions large areas of infected trees can be destroyed, leading to damage on an ecological scale. The interactions of B. xylophilus with plants are mediated by secreted effector proteins produced in the pharyngeal gland cells. Identification of effectors is important to understand mechanisms of parasitism and to develop new control measures for the pathogens.

RESULTS: Using an approach pioneered in cyst nematodes, we have analysed the promoter regions of a small panel of previously validated pharyngeal gland cell effectors from B. xylophilus to identify an associated putative regulatory promoter motif: STATAWAARS. The presence of STATAWAARS in the promoter region of an uncharacterized gene is a predictor that the corresponding gene encodes a putatively secreted protein, consistent with effector function. Furthermore, we are able to experimentally validate that a subset of STATAWAARS-containing genes are specifically expressed in the pharyngeal glands. Finally, we independently validate the association of STATAWAARS with tissue-specific expression by directly sequencing the mRNA of pharyngeal gland cells. We combine a series of criteria, including STATAWAARS predictions and abundance in the gland cell transcriptome, to generate a comprehensive effector repertoire for B. xylophilus. The genes highlighted by this approach include many previously described effectors and a series of novel "pioneer" effectors.

CONCLUSIONS: We provide a major scientific advance in the area of effector regulation. We identify a novel promoter motif (STATAWAARS) associated with expression in the pharyngeal gland cells. Our data, coupled with those from previous studies, suggest that lineage-specific promoter motifs are a theme of effector regulation in the phylum Nematoda.}, } @article {pmid30053750, year = {2018}, author = {Ranieri, MR and Whitchurch, CB and Burrows, LL}, title = {Mechanisms of biofilm stimulation by subinhibitory concentrations of antimicrobials.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {164-169}, doi = {10.1016/j.mib.2018.07.006}, pmid = {30053750}, issn = {1879-0364}, abstract = {Biofilms are a typical mode of growth for most microorganisms and provide them with a variety of survival benefits. Biofilms can pose medical and industrial challenges due to their increased tolerance of antimicrobials and disinfectants. Exposure of bacteria to subinhibitory concentrations of those compounds can further exacerbate the problem, as they provoke physiological changes that lead to increased biofilm production and potential therapeutic failure. The protected niche of a biofilm provides conditions that promote selection for persisters and resistant mutants. In this review we discuss our current understanding of the mechanisms underlying biofilm stimulation in response to subinhibitory antimicrobials, and how we might exploit this 'anti-antibiotic' phenotype to treat biofilm-related infections and discover new compounds.}, } @article {pmid30053216, year = {2018}, author = {}, title = {Evolution of Sex-Biased Gene Expression and Dosage Compensation in the Eye and Brain of Heliconius Butterflies.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy137}, pmid = {30053216}, issn = {1537-1719}, } @article {pmid30053206, year = {2018}, author = {Guffanti, G and Bartlett, A and Klengel, T and Klengel, C and Hunter, R and Glinsky, G and Macciardi, F}, title = {Novel Bioinformatics Approach Identifies Transcriptional Profiles of Lineage-Specific Transposable Elements at Distinct Loci in the Human Dorsolateral Prefrontal Cortex.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2435-2453}, pmid = {30053206}, issn = {1537-1719}, support = {R21 MH115327/MH/NIMH NIH HHS/United States ; }, abstract = {Expression of transposable elements (TE) is transiently activated during human preimplantation embryogenesis in a developmental stage- and cell type-specific manner and TE-mediated epigenetic regulation is intrinsically wired in developmental genetic networks in human embryos and embryonic stem cells. However, there are no systematic studies devoted to a comprehensive analysis of the TE transcriptome in human adult organs and tissues, including human neural tissues. To investigate TE expression in the human Dorsolateral Prefrontal Cortex (DLPFC), we developed and validated a straightforward analytical approach to chart quantitative genome-wide expression profiles of all annotated TE loci based on unambiguous mapping of discrete TE-encoded transcripts using a de novo assembly strategy. To initially evaluate the potential regulatory impact of DLPFC-expressed TE, we adopted a comparative evolutionary genomics approach across humans, primates, and rodents to document conservation patterns, lineage-specificity, and colocalizations with transcription factor binding sites mapped within primate- and human-specific TE. We identified 654,665 transcripts expressed from 477,507 distinct loci of different TE classes and families, the majority of which appear to have originated from primate-specific sequences. We discovered 4,687 human-specific and transcriptionally active TEs in DLPFC, of which the prominent majority (80.2%) appears spliced. Our analyses revealed significant associations of DLPFC-expressed TE with primate- and human-specific transcription factor binding sites, suggesting potential cross-talks of concordant regulatory functions. We identified 1,689 TEs differentially expressed in the DLPFC of Schizophrenia patients, a majority of which is located within introns of 1,137 protein-coding genes. Our findings imply that identified DLPFC-expressed TEs may affect human brain structures and functions following different evolutionary trajectories. On one side, hundreds of thousands of TEs maintained a remarkably high conservation for ∼8 My of primates' evolution, suggesting that they are likely conveying evolutionary-constrained primate-specific regulatory functions. In parallel, thousands of transcriptionally active human-specific TE loci emerged more recently, suggesting that they could be relevant for human-specific behavioral or cognitive functions.}, } @article {pmid30053133, year = {2018}, author = {Trujillo, JT and Seetharam, AS and Hufford, MB and Beilstein, MA and Mosher, RA}, title = {Evidence for a Unique DNA-Dependent RNA Polymerase in Cereal Crops.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2454-2462}, pmid = {30053133}, issn = {1537-1719}, support = {T32 GM008659/GM/NIGMS NIH HHS/United States ; }, abstract = {Gene duplication is an important driver for the evolution of new genes and protein functions. Duplication of DNA-dependent RNA polymerase (Pol) II subunits within plants led to the emergence of RNA Pol IV and V complexes, each of which possess unique functions necessary for RNA-directed DNA Methylation. Comprehensive identification of Pol V subunit orthologs across the monocot radiation revealed a duplication of the largest two subunits within the grasses (Poaceae), including critical cereal crops. These paralogous Pol subunits display sequence conservation within catalytic domains, but their carboxy terminal domains differ in length and character of the Ago-binding platform, suggesting unique functional interactions. Phylogenetic analysis of the catalytic region indicates positive selection on one paralog following duplication, consistent with retention via neofunctionalization. Positive selection on residue pairs that are predicted to interact between subunits suggests that paralogous subunits have evolved specific assembly partners. Additional Pol subunits as well as Pol-interacting proteins also possess grass-specific paralogs, supporting the hypothesis that a novel Pol complex with distinct function has evolved in the grass family, Poaceae.}, } @article {pmid30053121, year = {2018}, author = {Hoffmeier, A and Gramzow, L and Bhide, AS and Kottenhagen, N and Greifenstein, A and Schubert, O and Mummenhoff, K and Becker, A and Theißen, G}, title = {A Dead Gene Walking: Convergent Degeneration of a Clade of MADS-Box Genes in Crucifers.}, journal = {Molecular biology and evolution}, volume = {35}, number = {11}, pages = {2618-2638}, doi = {10.1093/molbev/msy142}, pmid = {30053121}, issn = {1537-1719}, abstract = {Genes are "born," and eventually they "die." These processes shape the phenotypic evolution of organisms and are hence of great biological interest. If genes die in plants, they generally do so quite rapidly. Here, we describe the fate of GOA-like genes that evolve in a dramatically different manner. GOA-like genes belong to the subfamily of Bsister genes of MIKC-type MADS-box genes. Typical MIKC-type genes encode conserved transcription factors controlling plant development. We show that ABS-like genes, a clade of Bsister genes, are indeed highly conserved in crucifers (Brassicaceae) maintaining the ancestral function of Bsister genes in ovule and seed development. In contrast, their closest paralogs, the GOA-like genes, have been undergoing convergent gene death in Brassicaceae. Intriguingly, erosion of GOA-like genes occurred after millions of years of coexistence with ABS-like genes. We thus describe Delayed Convergent Asymmetric Degeneration, a so far neglected but possibly frequent pattern of duplicate gene evolution that does not fit classical scenarios. Delayed Convergent Asymmetric Degeneration of GOA-like genes may have been initiated by a reduction in the expression of an ancestral GOA-like gene in the stem group of Brassicaceae and driven by dosage subfunctionalization. Our findings have profound implications for gene annotations in genomics, interpreting patterns of gene evolution and using genes in phylogeny reconstructions of species.}, } @article {pmid30053110, year = {2018}, author = {Burke, GR and Simmonds, TJ and Sharanowski, BJ and Geib, SM}, title = {Rapid Viral Symbiogenesis via Changes in Parasitoid Wasp Genome Architecture.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2463-2474}, doi = {10.1093/molbev/msy148}, pmid = {30053110}, issn = {1537-1719}, abstract = {Viral genome integration provides a complex route to biological innovation that has rarely but repeatedly occurred in one of the most diverse lineages of organisms on the planet, parasitoid wasps. We describe a novel endogenous virus in braconid wasps derived from pathogenic alphanudiviruses. Limited to a subset of the genus Fopius, this recent acquisition allows an unprecedented opportunity to examine early endogenization events. Massive amounts of virus-like particles (VLPs) are produced in wasp ovaries. Unlike most endogenous viruses of parasitoid wasps, the VLPs do not contain DNA, translating to major differences in parasitism-promoting strategies. Rapid changes include genomic rearrangement, loss of DNA processing proteins, and wasp control of viral gene expression. These events precede the full development of tissue-specific viral gene expression observed in older associations. These data indicate that viral endogenization can rapidly result in functional and evolutionary changes associated with genomic novelty and adaptation in parasitoids.}, } @article {pmid30053098, year = {2018}, author = {Flouri, T and Jiao, X and Rannala, B and Yang, Z}, title = {Species Tree Inference with BPP Using Genomic Sequences and the Multispecies Coalescent.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2585-2593}, pmid = {30053098}, issn = {1537-1719}, abstract = {The multispecies coalescent provides a natural framework for accommodating ancestral genetic polymorphism and coalescent processes that can cause different genomic regions to have different genealogical histories. The Bayesian program BPP includes a full-likelihood implementation of the multispecies coalescent, using transmodel Markov chain Monte Carlo to calculate the posterior probabilities of different species trees. BPP is suitable for analyzing multilocus sequence data sets and it accommodates the heterogeneity of gene trees (both the topology and branch lengths) among loci and gene tree uncertainties due to limited phylogenetic information at each locus. Here, we provide a practical guide to the use of BPP in species tree estimation. BPP is a command-line program that runs on linux, macosx, and windows. This protocol shows how to use both BPP 3.4 (http://abacus.gene.ucl.ac.uk/software/) and BPP 4.0 (https://github.com/bpp/).}, } @article {pmid30053041, year = {2018}, author = {Harwood, CR and Mouillon, JM and Pohl, S and Arnau, J}, title = {Secondary metabolite production and the safety of industrially important members of the Bacillus subtilis group.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {6}, pages = {721-738}, pmid = {30053041}, issn = {1574-6976}, mesh = {Bacillus licheniformis/genetics ; Bacillus subtilis/*genetics ; Bacteriological Techniques ; Genome, Bacterial/*genetics ; *Industrial Microbiology ; Peptides/genetics/metabolism/toxicity ; Polyketides ; }, abstract = {Members of the 'Bacillus subtilis group' include some of the most commercially important bacteria, used for the production of a wide range of industrial enzymes and fine biochemicals. Increasingly, group members have been developed for use as animal feed enhancers and antifungal biocontrol agents. The group has long been recognised to produce a range of secondary metabolites and, despite their long history of safe usage, this has resulted in an increased focus on their safety. Traditional methods used to detect the production of secondary metabolites and other potentially harmful compounds have relied on phenotypic tests. Such approaches are time consuming and, in some cases, lack specificity. Nowadays, accessibility to genome data and associated bioinformatical tools provides a powerful means for identifying gene clusters associated with the synthesis of secondary metabolites. This review focuses primarily on well-characterised strains of B. subtilis and B. licheniformis and their synthesis of non-ribosomally synthesised peptides and polyketides. Where known, the activities and toxicities of their secondary metabolites are discussed, together with the limitations of assays currently used to assess their toxicity. Finally, the regulatory framework under which such strains are authorised for use in the production of food and feed enzymes is also reviewed.}, } @article {pmid30052968, year = {2018}, author = {Medina, DA and Pinto, F and Ortuzar, V and Garrido, D}, title = {Simulation and modeling of dietary changes in the infant gut microbiome.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy140}, pmid = {30052968}, issn = {1574-6941}, abstract = {The early gut microbiome is essential for health, and diet has a profound influence in its composition. Oligosaccharides in breast milk or formula act as prebiotics, influencing gut microbiome structure. Here we simulated the impact of a dietary switch from fructooligosaccharides (FOS) to 2-fucosyllactose (2FL) in a continuous culture containing a consortium of species of the infant gut microbiome. During growth on FOS the consortium was dominated by Lactobacillus acidophilus, characterized by high amounts of lactate. Switching to 2FL led to a decrease in total biomass, and a recovery in Bifidobacterium infantis and Escherichia coli levels. While FOS was rapidly metabolized by the consortium, 2FL was utilized only after a delay. 2FL consumption was followed by a gradual switch from lactate to acetate. The activity of these bacterial species correlated well with gene expression analysis. Mathematical modeling of a multi-species consortium in continuous culture was capable to explain in great part the behavior of the system. The model was finally used to represent the outcome of the system after 48 h after each regime. This work highlights the impact of dietary changes in the gut microbiome, and provides a modeling framework to predict this influence.}, } @article {pmid30052954, year = {2018}, author = {Wiegand, S and Jogler, M and Jogler, C}, title = {On the maverick Planctomycetes.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {6}, pages = {739-760}, doi = {10.1093/femsre/fuy029}, pmid = {30052954}, issn = {1574-6976}, mesh = {Biological Evolution ; Cell Wall/chemistry ; Gram-Negative Bacteria/*classification/cytology ; Peptidoglycan/metabolism ; Planctomycetales/*classification/cytology ; Species Specificity ; }, abstract = {Planctomycetes are ubiquitous, environmentally and biotechnologically important bacteria that are key players in global carbon and nitrogen cycles. Ever since their first discovery in the 1920s they seemed to blur the prokaryote /eukaryote dichotomy. After initially being described as fungi and reclassified as bacteria later, they were still thought to feature a nucleus-like compartment surrounding their highly condensed DNA. Also, an endocytosis-like uptake mechanism for macromolecules was described. Besides these eukaryotic hallmark traits, Planctomycetes seemed to lack typical bacterial features such as a peptidoglycan cell wall or the universal bacterial cell division protein FtsZ, while mostly dividing by polar budding instead of binary fission. Thus, Planctomycetes were speculated to be ancestral to both, bacteria and eukaryotes. With the advent of novel microscopic techniques, along with the development of genetic tools for Planctomycetes, some of these hypotheses were revisited. Surprisingly, Planctomycetes were found to possess a peptidoglycan cell wall and to comprise a cell plan comparable to other Gram-negative bacteria as the nucleus-like structure is rather an invagination of the cytoplasmic membrane than a cohesive compartment. These finding challenge the idea of a eukaryotic ancestry of the phylum, as Planctomycetes now appear similar, yet distinct to other bacteria.}, } @article {pmid30052926, year = {2018}, author = {Stedtfeld, RD and Guo, X and Stedtfeld, TM and Sheng, H and Williams, MR and Hauschild, K and Gunturu, S and Tift, L and Wang, F and Howe, A and Chai, B and Yin, D and Cole, JR and Tiedje, JM and Hashsham, SA}, title = {Primer set 2.0 for highly parallel qPCR array targeting antibiotic resistance genes and mobile genetic elements.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy130}, pmid = {30052926}, issn = {1574-6941}, abstract = {The high-throughput antibiotic resistance gene (ARG) qPCR array, initially published in 2012, is increasingly used to quantify resistance and mobile determinants in environmental matrices. Continued utility of the array; however, necessitates improvements such as removing or redesigning questionable primer sets, updating targeted genes and coverage of available sequences. Towards this goal, a new primer design tool (EcoFunPrimer) was used to aid in identification of conserved regions of diverse genes. The total number of assays used for diverse genes was reduced from 91 old primer sets to 52 new primer sets, with only a 10% loss in sequence coverage. While the old and new array both contain 384 primer sets, a reduction in old primer sets permitted 147 additional ARGs and mobile genetic elements to be targeted. Results of validating the updated array with a mock community of strains resulted in over 98% of tested instances incurring true positive/negative calls. Common queries related to sensitivity, quantification and conventional data analysis (e.g. Ct cutoff value, and estimated genomic copies without standard curves) were also explored. A combined list of new and previously used primer sets is provided with a recommended set based on redesign of primer sets and results of validation.}, } @article {pmid30052910, year = {2018}, author = {Hussain, M and Hamid, MI and Tian, J and Hu, J and Zhang, X and Chen, J and Xiang, M and Liu, X}, title = {Bacterial community assemblages in the rhizosphere soil, root endosphere and cyst of soybean cyst nematode-suppressive soil challenged with nematodes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy142}, pmid = {30052910}, issn = {1574-6941}, abstract = {In disease-suppressive soil, plants rely upon mutualistic associations between roots and specific microbes for nutrient acquisition and disease suppression. Notably, the transmission of suppressiveness by the cysts of sugar beet cyst nematode from suppressive to conducive soils has been previously observed in greenhouse trials. However, our current understanding of the bacterial assemblages in the cyst, root endosphere and rhizosphere soil is still limited. To obtain insights into these bacterial microbiota assemblages, the bacterial communities inhabiting the plant-associated microhabitats and cysts in soybean cyst nematode (SCN)-suppressive soil were characterized by deep sequencing, using soybean grown under growth room conditions with additional SCN challenge. Clustering analysis revealed that the cyst bacterial community was closer to the root endosphere community than to the rhizosphere and bulk soil communities. Interestingly, the cyst bacterial community was initially established by the consecutive selection of bacterial taxa from the soybean root endosphere. We found a set of potential microbial consortia, such as Pasteuria, Pseudomonas, Rhizobium, and other taxa, that were consistently enriched in the rhizocompartments under SCN challenge, and more abundant in the cysts than in the bulk soil. Our results suggest that the soybean root-associated and cyst microbiota may cause the suppressiveness of SCN in suppressive soil.}, } @article {pmid30052904, year = {2018}, author = {Evans, JS and Erwin, PM and Shenkar, N and López-Legentil, S}, title = {A comparison of prokaryotic symbiont communities in nonnative and native ascidians from reef and harbor habitats.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy139}, pmid = {30052904}, issn = {1574-6941}, abstract = {Harbor systems represent passive gateways for the introduction of nonnative ascidians that compete with the surrounding benthos and may spread through localized dispersal, even populating adjacent natural reefs. To investigate the potential role of microbial symbionts in the success of ascidian introductions and spread, we evaluated the host-specificity of prokaryotic communities within two ascidian species commonly found off the North Carolina coast. Replicate samples of the native ascidian Eudistoma capsulatum, the nonnative ascidian Distaplia bermudensis, and seawater were collected from artificial (harbor) and natural reef substrates. Prokaryotic communities in seawater samples and ascidian tunics were characterized via next-generation sequencing of partial 16S rRNA gene sequences. Ascidian microbiomes clustered strongly in response to host species, with significant differences in community structure between the two species and seawater. Further, symbiont community structure differed significantly between native ascidians collected from artificial and natural habitats, though this was not the case for the nonnative species. These findings suggested that nonnative species possess stable microbial symbiont communities that may allow them to thrive in a wide range of habitats, while native species rely on the restructuring of their microbial communities with specific symbionts (e.g. Chelativorans) to survive under particular environmental conditions such as increased pollution.}, } @article {pmid30052889, year = {2018}, author = {Kumar, S and Herrmann, M and Blohm, A and Hilke, I and Frosch, T and Trumbore, SE and Küsel, K}, title = {Thiosulfate- and hydrogen-driven autotrophic denitrification by a microbial consortium enriched from groundwater of an oligotrophic limestone aquifer.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy141}, pmid = {30052889}, issn = {1574-6941}, abstract = {Despite its potentially high relevance for nitrate removal in freshwater environments limited in organic carbon, chemolithoautotrophic denitrification has rarely been studied in oligotrophic groundwater. Using thiosulfate and H2 as electron donors, we established a chemolithoautotrophic enrichment culture from groundwater of a carbonate-rock aquifer to get more insight into the metabolic repertoire, substrate turnover, and transcriptional activity of subsurface denitrifying consortia. The enriched consortium was dominated by representatives of the genus Thiobacillus along with denitrifiers related to Sulfuritalea hydrogenivorans, Sulfuricella denitrificans, Dechloromonas sp. and Hydrogenophaga sp., representing the consortium's capacity to use multiple inorganic electron donors. Microcosm experiments coupled with Raman gas spectroscopy demonstrated complete denitrification driven by reduced sulfur compounds and hydrogen without formation of N2O. The initial nitrate/thiosulfate ratio had a strong effect on nosZ transcriptional activity and on N2 formation, suggesting similar patterns of the regulation of gene expression as in heterotrophic denitrifiers. Sequence analysis targeting nirS and nosZ transcripts identified Thiobacillus denitrificans-related organisms as the dominant active nirS-type denitrifiers in the consortium. An additional assessment of the nirS-type denitrifier community in the groundwaterclearly confirmed the potential for sulfur- and hydrogen-dependent chemolithoautotrophic denitrification as important metabolic feature widely spread among subsurface denitrifiers at the Hainich Critical Zone Exploratory.}, } @article {pmid30051891, year = {2018}, author = {Iglesias, N and Currie, MA and Jih, G and Paulo, JA and Siuti, N and Kalocsay, M and Gygi, SP and Moazed, D}, title = {Automethylation-induced conformational switch in Clr4 (Suv39h) maintains epigenetic stability.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {504-508}, pmid = {30051891}, issn = {1476-4687}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; R01 GM072805/GM/NIGMS NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; P50 GM107618/GM/NIGMS NIH HHS/United States ; S10 OD021527/OD/NIH HHS/United States ; K01 DK098285/DK/NIDDK NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 GM067945/GM/NIGMS NIH HHS/United States ; }, abstract = {Histone H3 lysine 9 methylation (H3K9me) mediates heterochromatic gene silencing and is important for genome stability and the regulation of gene expression1-4. The establishment and epigenetic maintenance of heterochromatin involve the recruitment of H3K9 methyltransferases to specific sites on DNA, followed by the recognition of pre-existing H3K9me by the methyltransferase and methylation of proximal histone H35-11. This positive feedback loop must be tightly regulated to prevent deleterious epigenetic gene silencing. Extrinsic anti-silencing mechanisms involving histone demethylation or boundary elements help to limit the spread of inappropriate H3K9me12-15. However, how H3K9 methyltransferase activity is locally restricted or prevented from initiating random H3K9me-which would lead to aberrant gene silencing and epigenetic instability-is not fully understood. Here we reveal an autoinhibited conformation in the conserved H3K9 methyltransferase Clr4 (also known as Suv39h) of the fission yeast Schizosaccharomyces pombe that has a critical role in preventing aberrant heterochromatin formation. Biochemical and X-ray crystallographic data show that an internal loop in Clr4 inhibits the catalytic activity of this enzyme by blocking the histone H3K9 substrate-binding pocket, and that automethylation of specific lysines in this loop promotes a conformational switch that enhances the H3K9me activity of Clr4. Mutations that are predicted to disrupt this regulation lead to aberrant H3K9me, loss of heterochromatin domains and inhibition of growth, demonstrating the importance of the intrinsic inhibition and auto-activation of Clr4 in regulating the deposition of H3K9me and in preventing epigenetic instability. Conservation of the Clr4 autoregulatory loop in other H3K9 methyltransferases and the automethylation of a corresponding lysine in the human SUV39H2 homologue16 suggest that the mechanism described here is broadly conserved.}, } @article {pmid30051890, year = {2018}, author = {Hopkins, BD and Pauli, C and Du, X and Wang, DG and Li, X and Wu, D and Amadiume, SC and Goncalves, MD and Hodakoski, C and Lundquist, MR and Bareja, R and Ma, Y and Harris, EM and Sboner, A and Beltran, H and Rubin, MA and Mukherjee, S and Cantley, LC}, title = {Suppression of insulin feedback enhances the efficacy of PI3K inhibitors.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {499-503}, pmid = {30051890}, issn = {1476-4687}, support = {P01 CA117969/CA/NCI NIH HHS/United States ; U54 CA210184/CA/NCI NIH HHS/United States ; R01 GM041890/GM/NIGMS NIH HHS/United States ; R35 CA197588/CA/NCI NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; }, abstract = {Mutations in PIK3CA, which encodes the p110α subunit of the insulin-activated phosphatidylinositol-3 kinase (PI3K), and loss of function mutations in PTEN, which encodes a phosphatase that degrades the phosphoinositide lipids generated by PI3K, are among the most frequent events in human cancers1,2. However, pharmacological inhibition of PI3K has resulted in variable clinical responses, raising the possibility of an inherent mechanism of resistance to treatment. As p110α mediates virtually all cellular responses to insulin, targeted inhibition of this enzyme disrupts glucose metabolism in multiple tissues. For example, blocking insulin signalling promotes glycogen breakdown in the liver and prevents glucose uptake in the skeletal muscle and adipose tissue, resulting in transient hyperglycaemia within a few hours of PI3K inhibition. The effect is usually transient because compensatory insulin release from the pancreas (insulin feedback) restores normal glucose homeostasis3. However, the hyperglycaemia may be exacerbated or prolonged in patients with any degree of insulin resistance and, in these cases, necessitates discontinuation of therapy3-6. We hypothesized that insulin feedback induced by PI3K inhibitors may reactivate the PI3K-mTOR signalling axis in tumours, thereby compromising treatment effectiveness7,8. Here we show, in several model tumours in mice, that systemic glucose-insulin feedback caused by targeted inhibition of this pathway is sufficient to activate PI3K signalling, even in the presence of PI3K inhibitors. This insulin feedback can be prevented using dietary or pharmaceutical approaches, which greatly enhance the efficacy/toxicity ratios of PI3K inhibitors. These findings have direct clinical implications for the multiple p110α inhibitors that are in clinical trials and provide a way to increase treatment efficacy for patients with many types of tumour.}, } @article {pmid30051650, year = {2018}, author = {Müller, AL and Pelikan, C and de Rezende, JR and Wasmund, K and Putz, M and Glombitza, C and Kjeldsen, KU and Jørgensen, BB and Loy, A}, title = {Bacterial interactions during sequential degradation of cyanobacterial necromass in a sulfidic arctic marine sediment.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2927-2940}, pmid = {30051650}, issn = {1462-2920}, support = {FWF, P29426-B29 to KW//Austrian Science Fund/ ; P25111-B22 to AL//Austrian Science Fund/ ; DSS1431//CARD-FISH probe/ ; }, abstract = {Seafloor microorganisms impact global carbon cycling by mineralizing vast quantities of organic matter (OM) from pelagic primary production, which is predicted to increase in the Arctic because of diminishing sea ice cover. We studied microbial interspecies-carbon-flow during anaerobic OM degradation in arctic marine sediment using stable isotope probing. We supplemented sediment incubations with 13 C-labeled cyanobacterial necromass (spirulina), mimicking fresh OM input, or acetate, an important OM degradation intermediate and monitored sulfate reduction rates and concentrations of volatile fatty acids (VFAs) during substrate degradation. Sequential 16S rRNA gene and transcript amplicon sequencing and fluorescence in situ hybridization combined with Raman microspectroscopy revealed that only few bacterial species were the main degraders of 13 C-spirulina necromass. Psychrilyobacter, Psychromonas, Marinifilum, Colwellia, Marinilabiaceae and Clostridiales species were likely involved in the primary hydrolysis and fermentation of spirulina. VFAs, mainly acetate, produced from spirulina degradation were mineralized by sulfate-reducing bacteria and an Arcobacter species. Cellular activity of Desulfobacteraceae and Desulfobulbaceae species during acetoclastic sulfate reduction was largely decoupled from relative 16S rRNA gene abundance shifts. Our findings provide new insights into the identities and physiological constraints that determine the population dynamics of key microorganisms during complex OM degradation in arctic marine sediments.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid30051643, year = {2018}, author = {García, FC and Calleja, ML and Al-Otaibi, N and Røstad, A and Morán, XAG}, title = {Diel dynamics and coupling of heterotrophic prokaryotes and dissolved organic matter in epipelagic and mesopelagic waters of the central Red Sea.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2990-3000}, doi = {10.1111/1462-2920.14336}, pmid = {30051643}, issn = {1462-2920}, abstract = {The ecological status of an ecosystem can be approached by the taxa present but also by the size of individual organisms. In aquatic ecosystems, flow cytometry (FC) allows to study the individual size spectra and broad community composition through the evaluation of cytometric categories. The Red Sea represents a warm oligotrophic environment with a strong diel signal of vertically migrating mesopelagic fish, which feed at night at the surface and release dissolved organic carbon (DOC) at depth during day-time. However, knowledge about how these conditions affect the dynamics of heterotrophic prokaryotes (HP) and their coupling with DOC is lacking. Here, we analyzed a high frequency sampling over 24 h to identify the community structure and compositional changes of HP in the epipelagic and mesopelagic layers of the central Red Sea. Our results show marked vertical and diel changes in HP communities in both layers. Specifically, the relative contribution of high nucleic acid content cells was remarkably linked to changes in DOC concentration and properties. The patterns observed were likely associated to the diel vertical migration of mesopelagic fish. These findings reveal that the structure of microbial communities in warm oligotrophic environments may be more dynamic than previously thought.}, } @article {pmid30051625, year = {2018}, author = {Docherty, KM and Pearce, DS and Lemmer, KM and Hale, RL}, title = {Distributing regionally, distinguishing locally: examining the underlying effects of local land use on airborne bacterial biodiversity.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3529-3542}, doi = {10.1111/1462-2920.14307}, pmid = {30051625}, issn = {1462-2920}, support = {1550748//Directorate for Biological Sciences/ ; //Western Michigan University College of Arts and Sciences/ ; //Western Michigan University Lee Honors College Fellowship Program/ ; //Western Michigan University College of Arts and Sciences Interdisciplinary Research Initiative Award/ ; //Michigan Space Grant Consortium Research Seed Grant/ ; 1550748//National Science Foundation/ ; }, abstract = {Airborne bacteria are abundant and can vary with land use. Urban expansion is increasing rapidly at a global scale, altering natural sources of airborne bacterial biodiversity, as soils and native plants are replaced by pavement and managed yards. Urbanization homogenizes the biodiversity of larger organisms, but its effects are understudied with respect to microbes. This study uses categorical and gradient approaches to examine airborne bacterial communities in southwest Michigan (USA). Airborne communities carried a gut-microbial signature and were equally homogenous above urban and rural sites, despite greater homogeneity of soil communities at urban sites. Ruminococcaceae were abundant, the source of which is likely wildlife. Beyond the gut-microbial signature, there were underlying effects of land use, which were evident in the shared airborne taxa across urban and rural sites. Bacillales, Burkholderiales, Alteromonadales and Pseudomonadales were shared more across urban sites, while Xanthomonadales, which contains crop-plant pathogens, were shared across rural agricultural sites. These results suggest that taxa which may distribute globally, coupled with localized sources, contribute to urban communities, while regional rural activities drive rural composition. We determined that soils were unlikely to contribute to broad distribution of some plant-associated taxa, but may be a source for distribution of others.}, } @article {pmid30051608, year = {2018}, author = {Lin, X and Wang, Y and Ma, X and Yan, Y and Wu, M and Bond, PL and Guo, J}, title = {Evidence of differential adaptation to decreased temperature by anammox bacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3514-3528}, doi = {10.1111/1462-2920.14306}, pmid = {30051608}, issn = {1462-2920}, support = {51522809//National Natural Science Foundation of China/ ; 51378370//National Natural Science Foundation of China/ ; PCRRY PCRRT16005//Foundation of the State Key Laboratory of Pollution Control and Resource Reuse/ ; }, abstract = {Low temperature is recognized as one of the major barriers for the application of the anaerobic ammonium oxidation (anammox) process to treat mainstream wastewater. Studies are yet to reveal the underlying biological limitations and molecular mechanisms associated with the inhibition of low temperature on the anammox process. In this study, metaproteomics was used to examine proteome modulation patterns of the anammox community occurring at different temperatures. The anammox community remarkably altered their proteomes when the temperature decreased from 35 °C to 20 °C. This was especially for proteins involved in energy conversion, transcription and translation and inorganic ion transport. However, at 15 °C the anammox activities became distinctly inhibited, and there was evidence of energy limitations and severe stress in Candidatus Kuenenia and to a lesser degree in Candidatus Brocadia. Candidatus Jettenia exhibited more changes in its proteome at 15 °C. From the proteomes, at the lower temperatures there was evidence of stress caused by toxic nitrogen compounds or reactive oxygen species in the anammox bacteria. Hydroxylamine oxidoreductase (HAO)-like proteins and an oxidative stress response protein (a catalase) were in high abundance to potentially ameliorate these inhibitory effects. This study offers metaproteomic insight into the anammox community-based physiological response to decreasing temperatures.}, } @article {pmid30051589, year = {2018}, author = {Yi, Y and Li, Z and Song, C and Kuipers, OP}, title = {Exploring plant-microbe interactions of the rhizobacteria Bacillus subtilis and Bacillus mycoides by use of the CRISPR-Cas9 system.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4245-4260}, doi = {10.1111/1462-2920.14305}, pmid = {30051589}, issn = {1462-2920}, support = {//China Scholarship Council/ ; //Dutch NWO-TTW program/ ; }, abstract = {Bacillus subtilis HS3 and Bacillus mycoides EC18 are two rhizosphere-associated bacteria with plant growth-promoting activity. The CRISPR-Cas9 system was implemented to study various aspects of plant-microbe interaction mechanisms of these two environmental isolates. The results show that fengycin and surfactin are involved in the antifungal activity of B. subtilis HS3. Moreover, this strain emits several other volatile organic compounds than 2,3-butanediol, contributing to plant growth promotion. Confocal laser scanning microscopy observations of the GFP-labelled strain showed that HS3 selectively colonizes root hairs of grass (Lolium perenne) in a hydroponic system. For B. mycoides EC18, we found that the wild-type EC18 strain and a ΔasbA (petropectin-deficient) mutant, but not the ΔdhbB (bacillibactin-deficient) and ADKO (asbA and dhbB double knockout) mutants, can increase the plant biomass and total chlorophyll. All the mutant strains have a reduced colonization capability on Chinese cabbage (Brassica rapa) roots, at the root tip and root hair region compared with the wild-type strain. These results indicate that the siderophore, bacillibactin, is involved in the plant growth promoting activity and could affect the root colonization of B. mycoides. Collectively, the CRISPR-Cas9 system we developed for environmental isolates is broadly applicable and will facilitate deciphering the mechanisms of Bacillus-plant interactions. © 2018 The Authors.}, } @article {pmid30051576, year = {2018}, author = {Kuhnert, E and Li, Y and Lan, N and Yue, Q and Chen, L and Cox, RJ and An, Z and Yokoyama, K and Bills, GF}, title = {Enfumafungin synthase represents a novel lineage of fungal triterpene cyclases.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3325-3342}, pmid = {30051576}, issn = {1462-2920}, support = {//National Institute of General Medical Sciences/ ; //Deutscher Akademischer Austauschdienst/ ; R01 GM121458/GM/NIGMS NIH HHS/United States ; INST 187/621//Deutsche Forschungsgemeinschaft/ ; //University of Texas Health Science Centre at Houston/ ; //Kay and Ben Fortson Endowment/ ; AU-20030616//Robert Welch Foundation/ ; R01 GM115729/GM/NIGMS NIH HHS/United States ; }, abstract = {Enfumafungin is a glycosylated fernene-type triterpenoid produced by the fungus Hormonema carpetanum. Its potent antifungal activity, mediated by its interaction with β-1,3-glucan synthase and the fungal cell wall, has led to its development into the semi-synthetic clinical candidate, ibrexafungerp (=SCY-078). We report on the preliminary identification of the enfumafungin biosynthetic gene cluster (BGC) based on genome sequencing, phylogenetic reconstruction, gene disruption, and cDNA sequencing studies. Enfumafungin synthase (efuA) consists of a terpene cyclase domain (TC) fused to a glycosyltransferase (GT) domain and thus represents a novel multifunctional enzyme. Moreover, the TC domain bears a phylogenetic relationship to bacterial squalene-hopene cyclases (SHC) and includes a typical DXDD motif within the active centre suggesting that efuA evolved from SHCs. Phylogenetic reconstruction of the GT domain indicated that this portion of the fusion gene originated from fungal sterol GTs. Eleven genes flanking efuA are putatively involved in the biosynthesis, regulation, transport and self-resistance of enfumafungin and include an acetyltransferase, three P450 monooxygenases, a dehydrogenase, a desaturase and a reductase. A hypothetical scheme for enfumafungin assembly is proposed in which the E-ring is oxidatively cleaved to yield the four-ring system of enfumafungin. EfuA represents the first member of a widespread lineage of fungal SHCs.}, } @article {pmid30051572, year = {2018}, author = {Fernández, M and Corral-Lugo, A and Krell, T}, title = {The plant compound rosmarinic acid induces a broad quorum sensing response in Pseudomonas aeruginosa PAO1.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4230-4244}, doi = {10.1111/1462-2920.14301}, pmid = {30051572}, issn = {1462-2920}, support = {BIO2016-76779-P//Spanish Ministry for Economy and Competitiveness/ ; BIO2013-42297//Spanish Ministry for Economy and Competitiveness/ ; CVI-7335//Junta de Andalucía/ ; //Fondo Social Europeo/ ; //FEDER/ ; }, abstract = {The interference of plant compounds with bacterial quorum sensing (QS) is a major mechanism through which plants and bacteria communicate. However, little is known about the modes of action and effects on signal integrity during this type of communication. We have recently shown that the plant compound rosmarinic acid (RA) specifically binds to the Pseudomonas aeruginosa RhlR QS receptor. To determine the effect of RA on expression patterns, we carried out global RNA-seq analysis. The results show that RA induces the expression of 128 genes, amongst which many virulence factor genes. RA triggers a broad QS response because 88% of the induced genes are known to be controlled by QS, and because RA stimulated genes were found to be involved in all four QS signalling systems within P. aeruginosa. This finding was confirmed through the analysis of transcriptional fusions transferred to wt and a rhlI/lasI double mutant. RA did not induce gene expression in the rhlI/lasI/rhlR triple mutant indicating that the effects observed are due to the RA-RhlR interaction. Furthermore, RA induced seven sRNAs that were all encoded in regions close to QS and/or RA induced genes. This work significantly enhances our understanding of plant bacteria interaction.}, } @article {pmid30051571, year = {2018}, author = {McCallin, S and Sarker, SA and Sultana, S and Oechslin, F and Brüssow, H}, title = {Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo-controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3278-3293}, doi = {10.1111/1462-2920.14310}, pmid = {30051571}, issn = {1462-2920}, abstract = {Bacteriophage therapy is a commonly used treatment for Staphylococcus aureus infections in countries of the former Soviet Union, using both single phages and phage cocktails. The scarce data available on Eastern phage cocktails prompted an investigation into commercially-available Pyophage cocktails from two different manufacturers used to treat skin and wound infections. Comparison of the metagenomic composition of two Pyophage products from Georgia and Russia revealed substantial differences in phage-types targeting Escherichia, Enterococcus, Salmonella, Pseudomonas aeruginosa and Proteus, therefore indicating multiple strategies for composing phage cocktails against these bacterial pathogens. Closely-related Kayvirus-like Myoviruses were, however, a shared component against S. aureus within all products, except for the inclusion of a secondary S. aureus Podovirus in one Microgen cocktail. Metagenomic analysis also revealed the presence of several probable prophage sequences but detected no genetic safety risks in terms of virulence factors or antibiotic resistance genes. The safety of broad-spectrum cocktails was tested by comparing the effects of nasal and oral exposure to Eliava Pyophage, a monospecies counterpart and placebo in healthy human carriers of S. aureus. The lack of adverse effects in any treatment groups supports the clinical safety of S. aureus phages administered as a single phage or as phage cocktail.}, } @article {pmid30051570, year = {2018}, author = {Deng, Y and Ning, D and Qin, Y and Xue, K and Wu, L and He, Z and Yin, H and Liang, Y and Buzzard, V and Michaletz, ST and Zhou, J}, title = {Spatial scaling of forest soil microbial communities across a temperature gradient.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3504-3513}, doi = {10.1111/1462-2920.14303}, pmid = {30051570}, issn = {1462-2920}, support = {31540071//National Natural Science Foundation of China/ ; 2016YFC0500702//China National Key Research and Development Program/ ; XDB15010302//Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)/ ; //CAS 100 talent program/ ; NSF EF-1065844//U.S. National Science Foundation MacroSystems Biology program/ ; 41430856//Collaborative Innovation Center for Regional Environmental Quality at the Tsinghua University and the National Science Foundation of China/ ; }, abstract = {Temperature is an important correlate of global patterns of biodiversity, yet the mechanisms driving these relationships are not well understood. Taxa-area relationships (TARs) have been intensively examined, but the effects of temperature on TARs, particularly for microbial communities, are largely undocumented. Here we present a continental-scale description of temperature-dependent nested TARs of microbial communities (bacteria and archaea) from soils of six forest sites spanning a temperature gradient from subalpine Colorado to tropical Panama. Our results revealed that spatial scaling rates (z-values) of microbial communities varied with both taxonomic resolutions and phylogenetic groups. Additionally, microbial TAR z-values increased with temperature (r = 0.739, P < 0.05), but were not correlated with other environmental variables tested (P > 0.05), indicating that microbial spatial scaling rate is temperature-dependent. Understanding how temperature affects the spatial scaling of microbial biodiversity is of fundamental importance for preservation of soil biodiversity and management of ecosystems.}, } @article {pmid30051569, year = {2018}, author = {Hassell, N and Tinker, KA and Moore, T and Ottesen, EA}, title = {Temporal and spatial dynamics in microbial community composition within a temperate stream network.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3560-3572}, doi = {10.1111/1462-2920.14311}, pmid = {30051569}, issn = {1462-2920}, support = {UG1025GR182025//University of Georgia/ ; }, abstract = {The water column of streams hosts a unique microbial community that is distinct from the microbial communities of the stream benthos and surrounding soil. This community is shaped by complex interacting forces, including microbial dispersal from surrounding environments and in-stream selection. However, how the processes structuring stream communities change over space and time remains poorly understood. In this study, we characterize spatial and temporal trends in microbial community composition throughout a stream network spanning first through fifth order streams. We found that the microbial communities of headwater streams are compositionally diverse, with low representation of freshwater microbial taxa and high representation of soil and sediment-associated taxa. In three out of five seasonal samplings, a successional pattern was identified in which phylotype richness and compositional heterogeneity decreased while the proportion of known freshwater taxa increased with increasing cumulative upstream dendritic distance. However, in two samplings, streams instead exhibited uniformly high microbial diversity across the watershed, and the fraction of freshwater taxa showed no relationship with dendritic distance. Overall, our data suggest that the successional processes that drive microbial diversity in streams are highly dynamic and can be disrupted at landscape scales, potentially in response to variation in temperature and precipitation.}, } @article {pmid30051568, year = {2018}, author = {Wang, G and Sun, P and Gong, Z and Gu, L and Lou, Y and Fang, W and Zhang, L and Su, L and Yang, T and Wang, B and Zhou, J and Xu, JR and Wang, Z and Zheng, W}, title = {Srk1 kinase, a SR protein-specific kinase, is important for sexual reproduction, plant infection and pre-mRNA processing in Fusarium graminearum.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3261-3277}, doi = {10.1111/1462-2920.14299}, pmid = {30051568}, issn = {1462-2920}, support = {31670142//National Natural Science Foundation of China/ ; 31701743//National Natural Science Foundation of China/ ; }, abstract = {SR protein-specific kinases (SRPKs) uniquely with a spacer region are important splicing factors from yeast to human. However, little is known about their biological functions in filamentous fungi. Therefore, we characterized a SRPK called SRK1 in wheat scab fungus Fusarium graminearum. Our data showed that Srk1 is required for vegetative growth, sexual reproduction and plant infection, and plays critical roles in pre-mRNA alternative splicing and gene expression. Remarkably, we found that Srk1 displayed dynamic shuttling between cytoplasm and the nucleus, which is regulated by the divergent spacer domain rather than its kinase activity, suggesting a regulatory mechanism for Srk1. Interestingly, Srk1-GFP also localized to the septal pores, indicating a possible role of Srk1 unrelated to mRNA processing. Although both K1 and K2 lobes of the kinase domain are essential for Srk1 functions, the K2 but not K1 lobe is responsible for the septal pore localization. Lastly, we established that Srk1 physically interacts with the two SR proteins, FgNpl3 and FgSrp1. Overall, our results indicated that SRK1 regulates fungal development, plant infection and mRNA processing by phosphorylation of other splicing factors including SR proteins, and the spacer domain regulates the functions of Srk1 by modulating its nucleocytoplasmic shuttling.}, } @article {pmid30051567, year = {2018}, author = {Kraková, L and Šoltys, K and Puškárová, A and Bučková, M and Jeszeová, L and Kucharík, M and Budiš, J and Orovčík, LU and Szemes, T and Pangallo, D}, title = {The microbiomes of a XVIII century mummy from the castle of Krásna Hôrka (Slovakia) and its surrounding environment.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3294-3308}, doi = {10.1111/1462-2920.14312}, pmid = {30051567}, issn = {1462-2920}, support = {2/0061/17//VEGA/ ; 26240120027//ITMS/ ; //OPRaD/ ; //ERDF/ ; }, abstract = {This microbiological survey was performed to determine the conservation state of a mummy in the Slovak castle of Krásna Hôrka and its surrounding environment. Culture-dependent identification was coupled with biodegradation assays on keratin, gelatin and cellulose. Next Generation Sequencing (NGS) using Illumina platform was used for a deeper microbial investigation. Three environmental samples were collected: from the glass of the sarcophagus, from the air inside it, and from the air of the chapel where the mummy is located. Seven different samples were taken from mummy's surface: from the left ear, left-hand palm, left-hand nail, left instep, right hand, abdomen and mineral crystals embedded within the skin. Three internal organ samples, from the lung, pleura and stomach, were also included in this study. Together, the culture-dependent and culture-independent analyses revealed that the bacterial communities present had fewer taxa than the fungal ones. The mycobiome showed the largest variability and included Epicoccum nigrum, Penicillium spp., Alternaria spp., Aspergillus spp., Cladosporium spp. and Aureobasidium pullulans; many other Ascomycota and Basidiomycota genera were detected by NGS. The most interesting results came from the skin mineral crystals and the internal organs. The hydrolytic assays revealed those microorganisms which might be considered dangerous 'mummy pathogens'. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid30051563, year = {2018}, author = {Himmelberg, AM and Brüls, T and Farmani, Z and Weyrauch, P and Barthel, G and Schrader, W and Meckenstock, RU}, title = {Anaerobic degradation of phenanthrene by a sulfate-reducing enrichment culture.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3589-3600}, doi = {10.1111/1462-2920.14335}, pmid = {30051563}, issn = {1462-2920}, support = {666952//ERC Advanced Grant/ ; }, abstract = {Anaerobic degradation processes are very important to attenuate polycyclic aromatic hydrocarbons (PAHs) in saturated, anoxic sediments. However, PAHs are poorly degradable, leading to very slow microbial growth and thus resulting in only a few cultures that have been enriched and studied so far. Here, we report on a new phenanthrene-degrading, sulfate-reducing enrichment culture, TRIP1. Genome-resolved metagenomics and strain specific cell counting with FISH and flow cytometry indicated that the culture is dominated by a microorganism belonging to the Desulfobacteraceae family (60% of the community) and sharing 93% 16S rRNA sequence similarity to the naphthalene-degrading, sulfate-reducing strain NaphS2. The anaerobic degradation pathway was studied by metabolite analyses and revealed phenanthroic acid as the major intermediate consistent with carboxylation as the initial activation reaction. Further reduced metabolites were indicative of a stepwise reduction of the ring system. We were able to measure the presumed second enzyme reaction in the pathway, phenanthroate-CoA ligase, in crude cell extracts. The reaction was specific for 2-phenanthroic acid and did not transform other isomers. The present study provides first insights into the anaerobic degradation pathways of three-ringed PAHs. The biochemical strategy follows principles known from anaerobic naphthalene degradation, including carboxylation and reduction of the aromatic ring system.}, } @article {pmid30051562, year = {2018}, author = {Matilla, MA}, title = {Shedding light into the mechanisms of formation and resuscitation of persistent bacterial cells.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3129-3131}, doi = {10.1111/1462-2920.14334}, pmid = {30051562}, issn = {1462-2920}, } @article {pmid30051561, year = {2018}, author = {Wang, M and Ding, J and Sun, B and Zhang, J and Wyckoff, KN and Yue, H and Zhao, M and Liang, Y and Wang, X and Wen, C and Zhou, J and Yang, Y}, title = {Microbial responses to inorganic nutrient amendment overridden by warming: Consequences on soil carbon stability.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2509-2522}, doi = {10.1111/1462-2920.14239}, pmid = {30051561}, issn = {1462-2920}, abstract = {Eutrophication and climate warming, induced by anthropogenic activities, are simultaneously occurring worldwide and jointly affecting soil carbon stability. Therefore, it is of great interest to examine whether and how they interactively affect soil microbial community, a major soil carbon driver. Here, we showed that climate warming, simulated by southward transferring Mollisol soil in agricultural ecosystems from the cold temperate climate zone (N) to warm temperate climate (C) and subtropical climate zone (S), decreased soil organic matter (SOM) by 6%-12%. In contrast, amendment with nitrogen, phosphorus and potassium enhanced plant biomass by 97% and SOM by 6% at the N site, thus stimulating copiotrophic taxa but reducing oligotrophic taxa in relative abundance. However, microbial responses to nutrient amendment were overridden by soil transfer in that nutrient amendment had little effect at the C site but increased recalcitrant carbon-degrading fungal Agaricomycetes and Microbotryomycetes taxa derived from Basidiomycota by 4-17 folds and recalcitrant carbon-degrading genes by 23%-40% at the S site, implying a possible priming effect. Consequently, SOM at the S site was not increased by nutrient amendment despite increased plant biomass by 108%. Collectively, we demonstrate that soil transfer to warmer regions overrides microbial responses to nutrient amendment and weakens soil carbon sequestration.}, } @article {pmid30051560, year = {2018}, author = {Balmonte, JP and Teske, A and Arnosti, C}, title = {Structure and function of high Arctic pelagic, particle-associated and benthic bacterial communities.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2941-2954}, doi = {10.1111/1462-2920.14304}, pmid = {30051560}, issn = {1462-2920}, support = {AWI_PS80_01//Alfred Wegener Institute (AWI)/ ; CMG ARC-1025526//National Science Foundation/ ; OCE-1332881//National Science Foundation/ ; OCE-1736772//National Science Foundation/ ; //Howard Hughes Medical Institute Teaching Fellowship/ ; //UNC Dissertation Completion Fellowship/ ; }, abstract = {Arctic marine microbes are affected by environmental changes that may ultimately influence their functions in carbon cycling. Here, we investigated in concert the structure and enzymatic activities of pelagic, particle-associated and benthic bacterial communities in the central Arctic Ocean, and used these data to evaluate microbial structure-function relationships. Our findings showed influences of hydrographic conditions and particle association on community composition, and sharp pelagic-benthic contrasts. In addition to community compositional differences, regional and depth-related patterns in enzymatic activities were observed. Peptide hydrolysis rates were highest in surface waters, especially at ice-free and first year ice-covered regions, and decreased with depth. While the range of hydrolysed polysaccharides showed varying geographic patterns, particles often showed a wider spectrum of polysaccharide hydrolase activities. Summed benthic peptidase rates differed across stations but showed similar proportions of individual enzyme activities. Analysing for potential linkages between structure and function after subtracting the effect of environmental conditions revealed no direct link, indicating functional redundancy to carry out peptide hydrolysis among pelagic microbes. Thus, while community composition and activities are influenced by environmental conditions, bacterial functional redundancy suggests that compositional shifts - in response to the changing Arctic - may have complex and less predictable functional consequences than previously anticipated. © 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid30051558, year = {2018}, author = {Wilhelm, RC and Hanson, BT and Chandra, S and Madsen, E}, title = {Community dynamics and functional characteristics of naphthalene-degrading populations in contaminated surface sediments and hypoxic/anoxic groundwater.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3543-3559}, pmid = {30051558}, issn = {1462-2920}, support = {R01 CA129326/CA/NCI NIH HHS/United States ; //U.S. Department of Energy/ ; //National Science Foundation/ ; 5RO1 CA129326/GF/NIH HHS/United States ; }, abstract = {Earlier research on the biogeochemical factors affecting natural attenuation in coal-tar contaminated groundwater, at South Glens Falls, NY, revealed the importance of anaerobic metabolism and trophic interactions between degrader and bacterivore populations. Field-based characterizations of both phenomena have proven challenging, but advances in stable isotope probing (SIP), single-cell imaging and shotgun metagenomics now provide cultivation-independent tools for their study. We tracked carbon from 13 C-labelled naphthalene through microbial populations in contaminated surface sediments over 6 days using respiration assays, secondary ion mass spectrometry imaging and shotgun metagenomics to disentangle the contaminant-based trophic web. Contaminant-exposed communities in hypoxic/anoxic groundwater were contrasted with those from oxic surface sediments to identify putative features of anaerobic catabolism of naphthalene. In total, six bacteria were responsible for naphthalene degradation. Cupriavidus, Ralstonia and Sphingomonas predominated at the earliest stages of SIP incubations and were succeeded in later stages by Stenotrophomonas and Rhodococcus. Metagenome-assembled genomes provided evidence for the ecological and functional characteristics underlying these temporal shifts. Identical species of Stenotrophomonas and Rhodococcus were abundant in the most contaminated, anoxic groundwater. Apparent increases in bacterivorous protozoa were observed following exposure to naphthalene, though insignificant amounts of carbon were transferred between bacterial degraders and populations of secondary feeders.}, } @article {pmid30051557, year = {2018}, author = {Xu, Y and Zhang, R and Wang, N and Cai, L and Tong, Y and Sun, Q and Chen, F and Jiao, N}, title = {Novel phage-host interactions and evolution as revealed by a cyanomyovirus isolated from an estuarine environment.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2974-2989}, doi = {10.1111/1462-2920.14326}, pmid = {30051557}, issn = {1462-2920}, support = {QNLM2016ORP0303//Qingdao National Laboratory for Marine Science and Technology/ ; 2017 M612256//China Postdoctoral Science Foundation/ ; 41522603, 31570172, 41706161//National Natural Science Foundation of China/ ; }, abstract = {Cyanophages are thought to affect the community structure, population dynamics, metabolic activity and evolution of picocyanobacteria and to impact the biogeochemical cycling in aquatic ecosystems. Here, we report an estuarine Synechococcus phage, S-CBWM1, which represents a novel viral lineage and exhibits interesting genetic features related to phage-host interactions and evolution. S-CBWM1 encapsidates four virion-associated proteins related to cellular metabolic regulation. Several novel auxiliary metabolic genes related to multidrug efflux, cell wall and capsule synthesis or modifications were also identified. In addition, the presence of the largest number of tRNA genes hitherto found in a phage genome may contribute to the translation efficiency of unique genes. These genomic and proteomic features of S-CBWM1 suggested phage-host interactions involved in adaptation to eutrophic estuarine environments. Phylogenetic and metagenomic analysis of the polγ gene in the S-CBWM1 genome provided new insights into the evolutionary path of mitochondrial DNA polymerase gamma. The S-CBWM1 psbA contains two group I introns, representing the first instance of multiple introns within psbA from phage. The isolation of S-CBWM1 reveals that estuarine ecosystems contain evolutionarily novel cyanophages that drive unique phage-host interactions.}, } @article {pmid30050064, year = {2018}, author = {Schiller, D and Monfils, MH and Raio, CM and Johnson, DC and LeDoux, JE and Phelps, EA}, title = {Addendum: Preventing the return of fear in humans using reconsolidation update mechanisms.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {E21}, doi = {10.1038/s41586-018-0405-7}, pmid = {30050064}, issn = {1476-4687}, } @article {pmid30049882, year = {2018}, author = {Sung, V}, title = {Let your stars shine.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {422}, doi = {10.1126/science.361.6400.422}, pmid = {30049882}, issn = {1095-9203}, } @article {pmid30049881, year = {2018}, author = {Poffenberger, MC and Metcalfe-Roach, A and Aguilar, E and Chen, J and Hsu, BE and Wong, AH and Johnson, RM and Flynn, B and Samborska, B and Ma, EH and Gravel, SP and Tonelli, L and Devorkin, L and Kim, P and Hall, A and Izreig, S and Loginicheva, E and Beauchemin, N and Siegel, PM and Artyomov, MN and Lum, JJ and Zogopoulos, G and Blagih, J and Jones, RG}, title = {LKB1 deficiency in T cells promotes the development of gastrointestinal polyposis.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {406-411}, doi = {10.1126/science.aan3975}, pmid = {30049881}, issn = {1095-9203}, support = {//CIHR/Canada ; }, mesh = {Adenomatous Polyps/*genetics/immunology/pathology ; Animals ; Chemokine CXCL2/genetics ; Gene Deletion ; Gene Expression ; Humans ; Inflammation/genetics/immunology/pathology ; Interleukin-11/genetics ; Interleukin-6/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Peutz-Jeghers Syndrome/*genetics/immunology/pathology ; Protein-Serine-Threonine Kinases/*genetics ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; Stomach Neoplasms/*genetics/immunology/pathology ; T-Lymphocytes/*immunology ; }, abstract = {Germline mutations in STK11, which encodes the tumor suppressor liver kinase B1 (LKB1), promote Peutz-Jeghers syndrome (PJS), a cancer predisposition syndrome characterized by the development of gastrointestinal (GI) polyps. Here, we report that heterozygous deletion of Stk11 in T cells (LThet mice) is sufficient to promote GI polyposis. Polyps from LThet mice, Stk11+/- mice, and human PJS patients display hallmarks of chronic inflammation, marked by inflammatory immune-cell infiltration, signal transducer and activator of transcription 3 (STAT3) activation, and increased expression of inflammatory factors associated with cancer progression [interleukin 6 (IL-6), IL-11, and CXCL2]. Targeting either T cells, IL-6, or STAT3 signaling reduced polyp growth in Stk11+/- animals. Our results identify LKB1-mediated inflammation as a tissue-extrinsic regulator of intestinal polyposis in PJS, suggesting possible therapeutic approaches by targeting deregulated inflammation in this disease.}, } @article {pmid30049880, year = {2018}, author = {Dinh, C and Farinholt, T and Hirose, S and Zhuchenko, O and Kuspa, A}, title = {Lectins modulate the microbiota of social amoebae.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {402-406}, doi = {10.1126/science.aat2058}, pmid = {30049880}, issn = {1095-9203}, support = {P01 HD039691/HD/NICHD NIH HHS/United States ; }, mesh = {Biological Transport ; DNA, Bacterial/metabolism ; Dictyostelium/*metabolism/*microbiology ; Discoidins/*metabolism ; Klebsiella pneumoniae/metabolism/*physiology ; Microbiota/*physiology ; Symbiosis ; }, abstract = {The social amoeba Dictyostelium discoideum maintains a microbiome during multicellular development; bacteria are carried in migrating slugs and as endosymbionts within amoebae and spores. Bacterial carriage and endosymbiosis are induced by the secreted lectin discoidin I that binds bacteria, protects them from extracellular killing, and alters their retention within amoebae. This altered handling of bacteria also occurs with bacteria coated by plant lectins and leads to DNA transfer from bacteria to amoebae. Thus, lectins alter the cellular response of D. discoideum to bacteria to establish the amoebae's microbiome. Mammalian cells can also maintain intracellular bacteria when presented with bacteria coated with lectins, so heterologous lectins may induce endosymbiosis in animals. Our results suggest that endogenous or environmental lectins may influence microbiome homeostasis across eukaryotic phylogeny.}, } @article {pmid30049879, year = {2018}, author = {Chandra, V and Fetter-Pruneda, I and Oxley, PR and Ritger, AL and McKenzie, SK and Libbrecht, R and Kronauer, DJC}, title = {Social regulation of insulin signaling and the evolution of eusociality in ants.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {398-402}, pmid = {30049879}, issn = {1095-9203}, support = {DP2 GM105454/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Ants/genetics/*growth & development/metabolism ; Biological Evolution ; Brain/metabolism ; Gene Expression ; Insulin/genetics/*metabolism ; Larva/genetics/growth & development/metabolism ; Reproduction ; Signal Transduction ; *Social Behavior ; }, abstract = {Queens and workers of eusocial Hymenoptera are considered homologous to the reproductive and brood care phases of an ancestral subsocial life cycle. However, the molecular mechanisms underlying the evolution of reproductive division of labor remain obscure. Using a brain transcriptomics screen, we identified a single gene, insulin-like peptide 2 (ilp2), which is always up-regulated in ant reproductives, likely because they are better nourished than their nonreproductive nestmates. In clonal raider ants (Ooceraea biroi), larval signals inhibit adult reproduction by suppressing ilp2, thus producing a colony reproductive cycle reminiscent of ancestral subsociality. However, increasing ILP2 peptide levels overrides larval suppression, thereby breaking the colony cycle and inducing a stable division of labor. These findings suggest a simple model for the origin of ant eusociality via nutritionally determined reproductive asymmetries potentially amplified by larval signals.}, } @article {pmid30049878, year = {2018}, author = {Tanaka, KZ and He, H and Tomar, A and Niisato, K and Huang, AJY and McHugh, TJ}, title = {The hippocampal engram maps experience but not place.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {392-397}, doi = {10.1126/science.aat5397}, pmid = {30049878}, issn = {1095-9203}, mesh = {Action Potentials ; Animals ; Brain Mapping ; CA1 Region, Hippocampal/cytology/*physiology ; *Memory, Episodic ; Mental Recall ; Mice ; Mice, Transgenic ; Neurons/*physiology ; Optogenetics ; Proto-Oncogene Proteins c-fos/analysis/genetics ; Theta Rhythm ; }, abstract = {Episodic memories are encoded by a sparse population of hippocampal neurons. In mice, optogenetic manipulation of this memory engram established that these neurons are indispensable and inducing for memory recall. However, little is known about their in vivo activity or precise role in memory. We found that during memory encoding, only a fraction of CA1 place cells function as engram neurons, distinguished by firing repetitive bursts paced at the theta frequency. During memory recall, these neurons remained highly context specific, yet demonstrated preferential remapping of their place fields. These data demonstrate a dissociation of precise spatial coding and contextual indexing by distinct hippocampal ensembles and suggest that the hippocampal engram serves as an index of memory content.}, } @article {pmid30049877, year = {2018}, author = {Popov, S and Shao, B and Bagdasarian, AL and Benton, TR and Zou, L and Yang, Z and Houk, KN and Nelson, HM}, title = {Teaching an old carbocation new tricks: Intermolecular C-H insertion reactions of vinyl cations.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {381-387}, doi = {10.1126/science.aat5440}, pmid = {30049877}, issn = {1095-9203}, abstract = {Vinyl carbocations have been the subject of extensive experimental and theoretical studies over the past five decades. Despite this long history in chemistry, the utility of vinyl cations in chemical synthesis has been limited, with most reactivity studies focusing on solvolysis reactions or intramolecular processes. Here we report synthetic and mechanistic studies of vinyl cations generated through silylium-weakly coordinating anion catalysis. We find that these reactive intermediates undergo mild intermolecular carbon-carbon bond-forming reactions, including carbon-hydrogen (C-H) insertion into unactivated sp3 C-H bonds and reductive Friedel-Crafts reactions with arenes. Moreover, we conducted computational studies of these alkane C-H functionalization reactions and discovered that they proceed through nonclassical, ambimodal transition structures. This reaction manifold provides a framework for the catalytic functionalization of hydrocarbons using simple ketone derivatives.}, } @article {pmid30049876, year = {2018}, author = {Brügmann, B}, title = {Fundamentals of numerical relativity for gravitational wave sources.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {366-371}, doi = {10.1126/science.aat3363}, pmid = {30049876}, issn = {1095-9203}, abstract = {Einstein's theory of general relativity affords an enormously successful description of gravity. The theory encodes the gravitational interaction in the metric, a tensor field on spacetime that satisfies partial differential equations known as the Einstein equations. This review introduces some of the fundamental concepts of numerical relativity-solving the Einstein equations on the computer-in simple terms. As a primary example, we consider the solution of the general relativistic two-body problem, which features prominently in the new field of gravitational wave astronomy.}, } @article {pmid30049875, year = {2018}, author = {Sanchez-Lengeling, B and Aspuru-Guzik, A}, title = {Inverse molecular design using machine learning: Generative models for matter engineering.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {360-365}, doi = {10.1126/science.aat2663}, pmid = {30049875}, issn = {1095-9203}, abstract = {The discovery of new materials can bring enormous societal and technological progress. In this context, exploring completely the large space of potential materials is computationally intractable. Here, we review methods for achieving inverse design, which aims to discover tailored materials from the starting point of a particular desired functionality. Recent advances from the rapidly growing field of artificial intelligence, mostly from the subfield of machine learning, have resulted in a fertile exchange of ideas, where approaches to inverse molecular design are being proposed and employed at a rapid pace. Among these, deep generative models have been applied to numerous classes of materials: rational design of prospective drugs, synthetic routes to organic compounds, and optimization of photovoltaics and redox flow batteries, as well as a variety of other solid-state materials.}, } @article {pmid30049874, year = {2018}, author = {Bottaro, S and Lindorff-Larsen, K}, title = {Biophysical experiments and biomolecular simulations: A perfect match?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {355-360}, doi = {10.1126/science.aat4010}, pmid = {30049874}, issn = {1095-9203}, mesh = {*Biophysical Phenomena ; Biophysics/*methods ; Models, Theoretical ; Molecular Conformation ; *Molecular Dynamics Simulation ; }, abstract = {A fundamental challenge in biological research is achieving an atomic-level description and mechanistic understanding of the function of biomolecules. Techniques for biomolecular simulations have undergone substantial developments, and their accuracy and scope have expanded considerably. Progress has been made through an increasingly tight integration of experiments and simulations, with experiments being used to refine simulations and simulations used to interpret experiments. Here we review the underpinnings of this progress, including methods for more efficient conformational sampling, accuracy of the physical models used, and theoretical approaches to integrate experiments and simulations. These developments are enabling detailed studies of complex biomolecular assemblies.}, } @article {pmid30049873, year = {2018}, author = {Kent, PRC and Kotliar, G}, title = {Toward a predictive theory of correlated materials.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {348-354}, doi = {10.1126/science.aat5975}, pmid = {30049873}, issn = {1095-9203}, abstract = {Correlated electron materials display a rich variety of notable properties ranging from unconventional superconductivity to metal-insulator transitions. These properties are of interest from the point of view of applications but are hard to treat theoretically, as they result from multiple competing energy scales. Although possible in more weakly correlated materials, theoretical design and spectroscopy of strongly correlated electron materials have been a difficult challenge for many years. By treating all the relevant energy scales with sufficient accuracy, complementary advances in Green's functions and quantum Monte Carlo methods open a path to first-principles computational property predictions in this class of materials.}, } @article {pmid30049872, year = {2018}, author = {Voosen, P}, title = {The Earth Machine.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {344-347}, doi = {10.1126/science.361.6400.344}, pmid = {30049872}, issn = {1095-9203}, } @article {pmid30049871, year = {2018}, author = {Funk, M and Norman, C and Smith, KT and Stajic, J and Yeston, J}, title = {Marvelous models.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {342-343}, doi = {10.1126/science.361.6400.342}, pmid = {30049871}, issn = {1095-9203}, } @article {pmid30049870, year = {2018}, author = {Lindenmayer, DB and Taylor, C}, title = {Where there is fire, there is smoke.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {341}, doi = {10.1126/science.aau6672}, pmid = {30049870}, issn = {1095-9203}, mesh = {*Fires ; *Smoke ; }, } @article {pmid30049869, year = {2018}, author = {Dijkstra, KB and Schrama, MJJ and Gorsich, EE and Hochkirch, A}, title = {"Deadly mosquito" or "living freshwater"?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {341}, doi = {10.1126/science.aau5573}, pmid = {30049869}, issn = {1095-9203}, mesh = {Animals ; Biodiversity ; Climate Change ; *Communicable Disease Control ; *Conservation of Natural Resources ; Culicidae/*physiology ; Fresh Water/*parasitology ; Humans ; Malaria/*prevention & control ; *Mosquito Control ; }, } @article {pmid30049868, year = {2018}, author = {Volcan, MV and Lanés, LEK}, title = {Brazilian killifishes risk extinction.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {340-341}, doi = {10.1126/science.aau5930}, pmid = {30049868}, issn = {1095-9203}, mesh = {Agriculture ; Animals ; Brazil ; *Endangered Species ; *Extinction, Biological ; *Killifishes ; Risk ; Urbanization ; }, } @article {pmid30049867, year = {2018}, author = {Contreras, JL}, title = {The anticommons at 20: Concerns for research continue.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {335-337}, doi = {10.1126/science.aat4684}, pmid = {30049867}, issn = {1095-9203}, mesh = {Biomedical Research/*legislation & jurisprudence ; *Intellectual Property ; }, } @article {pmid30049866, year = {2018}, author = {Eisenberg, DS}, title = {Paul D. Boyer (1918-2018).}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {334}, doi = {10.1126/science.aau6601}, pmid = {30049866}, issn = {1095-9203}, } @article {pmid30049865, year = {2018}, author = {Hollstein, PE and Shaw, RJ}, title = {Inflamed T cells and stroma drive gut tumors.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {332-333}, doi = {10.1126/science.aau4804}, pmid = {30049865}, issn = {1095-9203}, mesh = {Gastrointestinal Neoplasms ; Humans ; Intestinal Mucosa/*immunology ; *Lymphocyte Activation ; T-Lymphocytes ; }, } @article {pmid30049864, year = {2018}, author = {Kennedy, SH and Klumpp, DA}, title = {Hydrocarbon synthesis with vinyl cations.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {331-332}, doi = {10.1126/science.aau0809}, pmid = {30049864}, issn = {1095-9203}, mesh = {*Cations ; *Hydrocarbons ; }, } @article {pmid30049863, year = {2018}, author = {Plys, AJ and Kingston, RE}, title = {Dynamic condensates activate transcription.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {329-330}, doi = {10.1126/science.aau4795}, pmid = {30049863}, issn = {1095-9203}, } @article {pmid30049862, year = {2018}, author = {Knöpfel, T}, title = {Neurotechnology to address big questions.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {328-329}, doi = {10.1126/science.aau4705}, pmid = {30049862}, issn = {1095-9203}, mesh = {*Neurosciences ; }, } @article {pmid30049861, year = {2018}, author = {Soden, BJ and Collins, WD and Feldman, DR}, title = {Reducing uncertainties in climate models.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {326-327}, doi = {10.1126/science.aau1864}, pmid = {30049861}, issn = {1095-9203}, } @article {pmid30049860, year = {2018}, author = {Kornei, K}, title = {The trailblazer.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {322-325}, doi = {10.1126/science.361.6400.322}, pmid = {30049860}, issn = {1095-9203}, mesh = {Athletic Performance/*physiology ; Female ; Humans ; Running/*physiology ; Sex Factors ; Testosterone/*physiology ; *Transsexualism ; }, } @article {pmid30049859, year = {2018}, author = {Service, RF}, title = {Chipmakers look past Moore's law, and silicon.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {321}, doi = {10.1126/science.361.6400.321}, pmid = {30049859}, issn = {1095-9203}, } @article {pmid30049858, year = {2018}, author = {Clery, D}, title = {Lake spied deep below polar ice cap on Mars.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {320}, doi = {10.1126/science.361.6400.320}, pmid = {30049858}, issn = {1095-9203}, } @article {pmid30049857, year = {2018}, author = {Rochmyaningsih, D}, title = {Study of 'sea nomads' under fire in Indonesia.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {318-319}, doi = {10.1126/science.361.6400.318}, pmid = {30049857}, issn = {1095-9203}, } @article {pmid30049856, year = {2018}, author = {Cho, A}, title = {Electron-ion collider wins key endorsement.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {317-318}, doi = {10.1126/science.361.6400.317}, pmid = {30049856}, issn = {1095-9203}, } @article {pmid30049855, year = {2018}, author = {Wadman, M}, title = {Report details harassment by famed biologist.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {316-317}, doi = {10.1126/science.361.6400.316}, pmid = {30049855}, issn = {1095-9203}, mesh = {California ; Genetics ; Humans ; Sexual Harassment/*ethics ; Universities ; }, } @article {pmid30049854, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {314-315}, doi = {10.1126/science.361.6400.314}, pmid = {30049854}, issn = {1095-9203}, } @article {pmid30049853, year = {2018}, author = {Taylor, JM}, title = {A quantum future awaits.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {313}, doi = {10.1126/science.aau8256}, pmid = {30049853}, issn = {1095-9203}, } @article {pmid30049852, year = {2018}, author = {Schneider, FRN and Sana, H and Evans, CJ and Bestenlehner, JM and Castro, N and Fossati, L and Gräfener, G and Langer, N and Ramírez-Agudelo, OH and Sabín-Sanjulián, C and Simón-Díaz, S and Tramper, F and Crowther, PA and de Koter, A and de Mink, SE and Dufton, PL and Garcia, M and Gieles, M and Hénault-Brunet, V and Herrero, A and Izzard, RG and Kalari, V and Lennon, DJ and Maíz Apellániz, J and Markova, N and Najarro, F and Podsiadlowski, P and Puls, J and Taylor, WD and van Loon, JT and Vink, JS and Norman, C}, title = {Response to Comment on "An excess of massive stars in the local 30 Doradus starburst".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {}, doi = {10.1126/science.aat7032}, pmid = {30049852}, issn = {1095-9203}, mesh = {*Extraterrestrial Environment ; *Stars, Celestial ; Time ; }, abstract = {Farr and Mandel reanalyze our data, finding initial mass function slopes for high-mass stars in 30 Doradus that agree with our results. However, their reanalysis appears to underpredict the observed number of massive stars. Their technique results in more precise slopes than in our work, strengthening our conclusion that there is an excess of massive stars (>30 solar masses) in 30 Doradus.}, } @article {pmid30049851, year = {2018}, author = {Farr, WM and Mandel, I}, title = {Comment on "An excess of massive stars in the local 30 Doradus starburst".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {}, doi = {10.1126/science.aat6506}, pmid = {30049851}, issn = {1095-9203}, abstract = {Schneider et al (Reports, 5 January 2018, p. 69) used an ad hoc statistical method in their calculation of the stellar initial mass function. Adopting an improved approach, we reanalyze their data and determine a power-law exponent of [Formula: see text] Alternative assumptions regarding dataset completeness and the star formation history model can shift the inferred exponent to [Formula: see text] and [Formula: see text], respectively.}, } @article {pmid30049787, year = {2018}, author = {Lin, X and Rivenson, Y and Yardimci, NT and Veli, M and Luo, Y and Jarrahi, M and Ozcan, A}, title = {All-optical machine learning using diffractive deep neural networks.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {1004-1008}, doi = {10.1126/science.aat8084}, pmid = {30049787}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Deep learning has been transforming our ability to execute advanced inference tasks using computers. Here we introduce a physical mechanism to perform machine learning by demonstrating an all-optical diffractive deep neural network (D2NN) architecture that can implement various functions following the deep learning-based design of passive diffractive layers that work collectively. We created 3D-printed D2NNs that implement classification of images of handwritten digits and fashion products, as well as the function of an imaging lens at a terahertz spectrum. Our all-optical deep learning framework can perform, at the speed of light, various complex functions that computer-based neural networks can execute; will find applications in all-optical image analysis, feature detection, and object classification; and will also enable new camera designs and optical components that perform distinctive tasks using D2NNs.}, } @article {pmid30049786, year = {2018}, author = {Zaferani, S and Pérez-Rodríguez, M and Biester, H}, title = {Diatom ooze-A large marine mercury sink.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {797-800}, doi = {10.1126/science.aat2735}, pmid = {30049786}, issn = {1095-9203}, mesh = {Antarctic Regions ; Diatoms/*metabolism ; Geologic Sediments/*analysis ; Mercury/analysis/*metabolism ; Oceans and Seas ; Water Pollutants, Chemical/analysis/*metabolism ; }, abstract = {The role of algae for sequestration of atmospheric mercury in the ocean is largely unknown owing to a lack of marine sediment data. We used high-resolution cores from marine Antarctica to estimate Holocene global mercury accumulation in biogenic siliceous sediments (diatom ooze). Diatom ooze exhibits the highest mercury accumulation rates ever reported for the marine environment and provides a large sink of anthropogenic mercury, surpassing existing model estimates by as much as a factor of 7. Anthropogenic pollution of the Southern Ocean began ~150 years ago, and up to 20% of anthropogenic mercury emitted to the atmosphere may have been stored in diatom ooze. These findings reveal the crucial role of diatoms as a fast vector for mercury sequestration and diatom ooze as a large marine mercury sink.}, } @article {pmid30049785, year = {2018}, author = {Hu, A and Guo, JJ and Pan, H and Zuo, Z}, title = {Selective functionalization of methane, ethane, and higher alkanes by cerium photocatalysis.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {668-672}, doi = {10.1126/science.aat9750}, pmid = {30049785}, issn = {1095-9203}, abstract = {With the recent soaring production of natural gas, the use of methane and other light hydrocarbon feedstocks as starting materials in synthetic transformations is becoming increasingly economically attractive, although it remains chemically challenging. We report the development of photocatalytic C-H amination, alkylation, and arylation of methane, ethane, and higher alkanes under visible light irradiation at ambient temperature. High catalytic efficiency (turnover numbers up to 2900 for methane and 9700 for ethane) and selectivity were achieved using abundant, inexpensive cerium salts as photocatalysts. Ligand-to-metal charge transfer excitation generated alkoxy radicals from simple alcohols that in turn acted as hydrogen atom transfer catalysts. The mixed-phase gas/liquid reaction was adapted to continuous flow, enabling the efficient use of gaseous feedstocks in scalable photocatalytic transformations.}, } @article {pmid30049784, year = {2018}, author = {Shen, H and Li, Z and Jiang, Y and Pan, X and Wu, J and Cristofori-Armstrong, B and Smith, JJ and Chin, YKY and Lei, J and Zhou, Q and King, GF and Yan, N}, title = {Structural basis for the modulation of voltage-gated sodium channels by animal toxins.}, journal = {Science (New York, N.Y.)}, volume = {362}, number = {6412}, pages = {}, doi = {10.1126/science.aau2596}, pmid = {30049784}, issn = {1095-9203}, mesh = {Amino Acid Sequence ; Animals ; Cryoelectron Microscopy ; Insect Proteins/*antagonists & inhibitors/*chemistry/ultrastructure ; Ion Channel Gating/drug effects ; Periplaneta ; Protein Domains ; Saxitoxin/chemistry ; Spider Venoms/*chemistry ; Tetrodotoxin/chemistry ; Voltage-Gated Sodium Channel Blockers/*chemistry ; Voltage-Gated Sodium Channels/*chemistry/ultrastructure ; }, abstract = {Animal toxins that modulate the activity of voltage-gated sodium (Nav) channels are broadly divided into two categories-pore blockers and gating modifiers. The pore blockers tetrodotoxin (TTX) and saxitoxin (STX) are responsible for puffer fish and shellfish poisoning in humans, respectively. Here, we present structures of the insect Nav channel NavPaS bound to a gating modifier toxin Dc1a at 2.8 angstrom-resolution and in the presence of TTX or STX at 2.6-Å and 3.2-Å resolution, respectively. Dc1a inserts into the cleft between VSDII and the pore of NavPaS, making key contacts with both domains. The structures with bound TTX or STX reveal the molecular details for the specific blockade of Na+ access to the selectivity filter from the extracellular side by these guanidinium toxins. The structures shed light on structure-based development of Nav channel drugs.}, } @article {pmid30049707, year = {2018}, author = {Tamarit, I and Cuesta, JA and Dunbar, RIM and Sánchez, A}, title = {Cognitive resource allocation determines the organization of personal networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8316-8321}, pmid = {30049707}, issn = {1091-6490}, mesh = {Bayes Theorem ; *Cognition ; Female ; Humans ; Interpersonal Relations ; Male ; *Resource Allocation ; *Social Support ; }, abstract = {The typical human personal social network contains about 150 relationships including kin, friends, and acquaintances, organized into a set of hierarchically inclusive layers of increasing size but decreasing emotional intensity. Data from a number of different sources reveal that these inclusive layers exhibit a constant scaling ratio of [Formula: see text] While the overall size of the networks has been connected to our cognitive capacity, no mechanism explaining why the networks present a layered structure with a consistent scaling has been proposed. Here we show that the existence of a heterogeneous cost to relationships (in terms of time or cognitive investment), together with a limitation in the total capacity an individual has to invest in them, can naturally explain the existence of layers and, when the cost function is linear, explain the scaling between them. We develop a one-parameter Bayesian model that fits the empirical data remarkably well. In addition, the model predicts the existence of a contrasting regime in the case of small communities, such that the layers have an inverted structure (increasing size with increasing emotional intensity). We test the model with five communities and provide clear evidence of the existence of the two predicted regimes. Our model explains, based on first principles, the emergence of structure in the organization of personal networks and allows us to predict a rare phenomenon whose existence we confirm empirically.}, } @article {pmid30049706, year = {2018}, author = {He, Q and Naqvi, S and McLellan, H and Boevink, PC and Champouret, N and Hein, I and Birch, PRJ}, title = {Plant pathogen effector utilizes host susceptibility factor NRL1 to degrade the immune regulator SWAP70.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7834-E7843}, pmid = {30049706}, issn = {1091-6490}, support = {BB/G015244/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/K018183/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L026880/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cullin Proteins/genetics/immunology ; DNA-Binding Proteins/genetics/*immunology ; Gene Expression Regulation, Plant/genetics/immunology ; Phytophthora infestans/immunology ; Plant Diseases/genetics/immunology ; *Plant Immunity ; Plant Proteins/genetics/*immunology ; Proteolysis ; Tobacco/genetics/*immunology/microbiology ; }, abstract = {Plant pathogens deliver effectors into plant cells to suppress immunity. Whereas many effectors inactivate positive immune regulators, other effectors associate with negative regulators of immunity: so-called susceptibility (S) factors. Little is known about how pathogens exploit S factors to suppress immunity. Phytophthora infestans RXLR effector Pi02860 interacts with host protein NRL1, which is an S factor whose activity suppresses INF1-triggered cell death (ICD) and is required for late blight disease. We show that NRL1 interacts in yeast and in planta with a guanine nucleotide exchange factor called SWAP70. SWAP70 associates with endosomes and is a positive regulator of immunity. Virus-induced gene silencing of SWAP70 in Nicotiana benthamiana enhances P. infestans colonization and compromises ICD. In contrast, transient overexpression of SWAP70 reduces P. infestans infection and accelerates ICD. Expression of Pi02860 and NRL1, singly or in combination, results in proteasome-mediated degradation of SWAP70. Degradation of SWAP70 is prevented by silencing NRL1, or by mutation of Pi02860 to abolish its interaction with NRL1. NRL1 is a BTB-domain protein predicted to form the substrate adaptor component of a CULLIN3 ubiquitin E3 ligase. A dimerization-deficient mutant, NRL1NQ, fails to interact with SWAP70 but maintains its interaction with Pi02860. NRL1NQ acts as a dominant-negative mutant, preventing SWAP70 degradation in the presence of effector Pi02860, and reducing P. infestans infection. Critically, Pi02860 enhances the association between NRL1 and SWAP70 to promote proteasome-mediated degradation of the latter and, thus, suppress immunity. Preventing degradation of SWAP70 represents a strategy to combat late blight disease.}, } @article {pmid30049705, year = {2018}, author = {Lai, CY and Rallabandi, B and Perazzo, A and Zheng, Z and Smiddy, SE and Stone, HA}, title = {Foam-driven fracture.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8082-8086}, pmid = {30049705}, issn = {1091-6490}, abstract = {In hydraulic fracturing, water is injected at high pressure to crack shale formations. More sustainable techniques use aqueous foams as injection fluids to reduce the water use and wastewater treatment of conventional hydrofractures. However, the physical mechanism of foam fracturing remains poorly understood, and this lack of understanding extends to other applications of compressible foams such as fire-fighting, energy storage, and enhanced oil recovery. Here we show that the injection of foam is much different from the injection of incompressible fluids and results in striking dynamics of fracture propagation that are tied to the compressibility of the foam. An understanding of bubble-scale dynamics is used to develop a model for macroscopic, compressible flow of the foam, from which a scaling law for the fracture length as a function of time is identified and exhibits excellent agreement with our experimental results.}, } @article {pmid30049603, year = {2018}, author = {Branco, A and Francisco, D and Hanscheid, T}, title = {Is There a 'Normal' Oxygen Concentration for in vitro Plasmodium Cultures?.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {811-812}, doi = {10.1016/j.pt.2018.07.003}, pmid = {30049603}, issn = {1471-5007}, mesh = {In Vitro Techniques ; Oxygen/*chemistry ; Plasmodium/*growth & development ; }, } @article {pmid30049602, year = {2018}, author = {Findlater, A and Bogoch, II}, title = {Human Mobility and the Global Spread of Infectious Diseases: A Focus on Air Travel.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {772-783}, doi = {10.1016/j.pt.2018.07.004}, pmid = {30049602}, issn = {1471-5007}, abstract = {Greater human mobility, largely driven by air travel, is leading to an increase in the frequency and reach of infectious disease epidemics. Air travel can rapidly connect any two points on the planet, and this has the potential to cause swift and broad dissemination of emerging and re-emerging infectious diseases that may pose a threat to global health security. Investments to strengthen surveillance, build robust early-warning systems, improve predictive models, and coordinate public health responses may help to prevent, detect, and respond to new infectious disease epidemics.}, } @article {pmid30049587, year = {2018}, author = {San Millan, A}, title = {Evolution of Plasmid-Mediated Antibiotic Resistance in the Clinical Context.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {978-985}, doi = {10.1016/j.tim.2018.06.007}, pmid = {30049587}, issn = {1878-4380}, abstract = {Antibiotic-resistant infections are an urgent problem in clinical settings because they sharply increase mortality risk in critically ill patients. The horizontal spread of antibiotic resistance genes among bacteria is driven by bacterial plasmids, promoting the evolution of resistance. Crucially, particular associations exist between resistance plasmids and bacterial clones that become especially successful in clinical settings. However, the factors underlying the success of these associations remain unknown. Recent in vitro evidence reveals (i) that plasmids produce fitness costs in bacteria, and (ii) that these costs are alleviated over time through compensatory mutations. I argue that plasmid-imposed costs and subsequent compensatory adaptation may determine the success of associations between plasmids and bacteria in clinical settings, shaping the in vivo evolution of antibiotic resistance.}, } @article {pmid30049268, year = {2018}, author = {Arsenault-Labrecque, G and Sonah, H and Lebreton, A and Labbé, C and Marchand, G and Xue, A and Belzile, F and Knaus, BJ and Grünwald, NJ and Bélanger, RR}, title = {Stable predictive markers for Phytophthora sojae avirulence genes that impair infection of soybean uncovered by whole genome sequencing of 31 isolates.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {80}, pmid = {30049268}, issn = {1741-7007}, abstract = {BACKGROUND: The interaction between oomycete plant pathogen Phytophthora sojae and soybean is characterized by the presence of avirulence (Avr) genes in P. sojae, which encode for effectors that trigger immune responses and resistance in soybean via corresponding resistance genes (Rps). A recent survey highlighted a rapid diversification of P. sojae Avr genes in soybean fields and the need to deploy new Rps genes. However, the full genetic diversity of P. sojae isolates remains complex and dynamic and is mostly characterized on the basis of phenotypic associations with differential soybean lines.

RESULTS: We sequenced the genomes of 31 isolates of P. sojae, representing a large spectrum of the pathotypes found in soybean fields, and compared all the genetic variations associated with seven Avr genes (1a, 1b, 1c, 1d, 1k, 3a, 6) and how the derived haplotypes matched reported phenotypes in 217 interactions. We discovered new variants, copy number variations and some discrepancies with the virulence of previously described isolates with Avr genes, notably with Avr1b and Avr1c. In addition, genomic signatures revealed 11.5% potentially erroneous phenotypes. When these interactions were re-phenotyped, and the Avr genes re-sequenced over time and analyzed for expression, our results showed that genomic signatures alone accurately predicted 99.5% of the interactions.

CONCLUSIONS: This comprehensive genomic analysis of seven Avr genes of P. sojae in a population of 31 isolates highlights that genomic signatures can be used as accurate predictors of phenotypes for compatibility with Rps genes in soybean. Our findings also show that spontaneous mutations, often speculated as a source of aberrant phenotypes, did not occur within the confines of our experiments and further suggest that epigenesis or gene silencing do not account alone for previous discordance between genotypes and phenotypes. Furthermore, on the basis of newly identified virulence patterns within Avr1c, our results offer an explanation why Rps1c has failed more rapidly in the field than the reported information on virulence pathotypes.}, } @article {pmid30049264, year = {2018}, author = {Münch, C}, title = {The different axes of the mammalian mitochondrial unfolded protein response.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {81}, pmid = {30049264}, issn = {1741-7007}, abstract = {Mitochondria are sensitive to numerous environmental stresses, which can lead to activation of mitochondrial stress responses (MSRs). Of particular recent interest has been the mitochondrial unfolded protein response (UPRmt), activated to restore protein homeostasis (proteostasis) upon mitochondrial protein misfolding. Several axes of the UPRmt have been described, creating some confusion as to the nature of the different responses. While distinct molecularly, these different axes are likely mutually beneficial and activated in parallel. This review aims at describing and distinguishing the different mammalian MSR/UPRmt axes to define key processes and members and to examine the involvement of protein misfolding.}, } @article {pmid30048641, year = {2018}, author = {Kowalchuk, AM and Maurer, KA and Shoja-Taheri, F and Brown, NL}, title = {Requirements for Neurogenin2 during mouse postnatal retinal neurogenesis.}, journal = {Developmental biology}, volume = {442}, number = {2}, pages = {220-235}, pmid = {30048641}, issn = {1095-564X}, support = {P30 EY012576/EY/NEI NIH HHS/United States ; R01 EY013612/EY/NEI NIH HHS/United States ; T32 EY015387/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/*metabolism ; Cell Differentiation/physiology ; Female ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Nerve Tissue Proteins/*metabolism ; Neurogenesis/physiology ; Pregnancy ; Repressor Proteins/genetics ; Retina/*cytology/growth & development ; Retinal Cone Photoreceptor Cells/cytology/metabolism ; Retinal Neurons/cytology/*metabolism ; Retinal Rod Photoreceptor Cells/metabolism ; Transcription Factors/genetics ; }, abstract = {During embryonic retinal development, the bHLH factor Neurog2 regulates the temporal progression of neurogenesis, but no role has been assigned for this gene in the postnatal retina. Using Neurog2 conditional mutants, we found that Neurog2 is necessary for the development of an early, embryonic cohort of rod photoreceptors, but also required by both a subset of cone bipolar subtypes, and rod bipolars. Using transcriptomics, we identified a subset of downregulated genes in P2 Neurog2 mutants, which act during rod differentiation, outer segment morphogenesis or visual processing. We also uncovered defects in neuronal cell culling, which suggests that the rod and bipolar cell phenotypes may arise via more complex mechanisms rather than a simple cell fate shift. However, given an overall phenotypic resemblance between Neurog2 and Blimp1 mutants, we explored the relationship between these two factors. We found that Blimp1 is downregulated between E12-birth in Neurog2 mutants, which probably reflects a dependence on Neurog2 in embryonic progenitor cells. Overall, we conclude that the Neurog2 gene is expressed and active prior to birth, but also exerts an influence on postnatal retinal neuron differentiation.}, } @article {pmid30048640, year = {2018}, author = {Le Douarin, NM and Dupin, E}, title = {The "beginnings" of the neural crest.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.07.019}, pmid = {30048640}, issn = {1095-564X}, abstract = {FOREWORD: The neural crest has been the main object of my investigations during my career in science, up to now. It is a fascinating topic for an embryologist because of its two unique characteristics: its large degree of multipotency and the fact that its development involves a phase during which its component cells migrate all over the embryo and settle in elected sites where they differentiate into a large variety of cell types. Thus, neural crest development raises several specific questions that are at the same time, of general interest: what are the mechanisms controlling the migratory behavior of the cells that detach from the neural plate borders? What are the migration routes taken by the neural crest cells and the environmental factors that make these cells stop in elected sites where they differentiate into a definite series of cell types? When I started to be interested in the neural crest, in the late 1960s, this embryonic structure was the subject of investigations of only a small number of developmental biologists. Fifty years later, it has become the center of interest of many laboratories over the world. The 150th anniversary of its discovery is a relevant opportunity to consider the progress that has been accomplished in our knowledge on the development of this ubiquitous structure, the roles it plays in the physiology of the organism through its numerous and widespread derivatives and its relationships with its environment, as well as the evolutionary advantages it has conferred to the vertebrate phylum. I wish to thank Pr Marianne Bronner, Chief Editor of Developmental Biology and Special Issue Guest Editor, for dedicating a special issue of this journal to this particular structure of the vertebrate embryo. In the following pages, Elisabeth Dupin and I will report some of the highlights of our own acquaintance with the neural crest of the avian embryo, after retracing the main trends of the discoveries of the historical pioneers.}, } @article {pmid30047254, year = {2018}, author = {Biagi, E and D'Amico, F and Soverini, M and Angelini, V and Barone, M and Turroni, S and Rampelli, S and Pari, S and Brigidi, P and Candela, M}, title = {Faecal bacterial communities from Mediterranean loggerhead sea turtles (Caretta caretta).}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12683}, pmid = {30047254}, issn = {1758-2229}, support = {LIFE12 NAT/IT/000937//LIFE-EU project TartaLife/ ; }, abstract = {The loggerhead sea turtle (Caretta caretta) is the most widespread sea turtle species in the Mediterranean Sea and a relevant pollution 'flagship species'. Here, we profiled the faecal microbiota from 29 C. caretta from a rescue centre, and explored the impact of several variables linked to both the animal itself and the environment (i.e., tank water ecosystem). We show that loggerhead turtles share more gut microbiota features with carnivorous marine mammals, than with phylogenetically close, but herbivorous, turtles, as a confirmation of the gut microbiota adaptive function to diet and environment. We also highlight a relation between the microbiota composition and the size (and consequently the age) of the turtles. Finally, we point out that the gut microbiota of sea turtles shows unexpectedly low exchange of microbes with the aquatic environment and is resilient to the stress induced by short-time captivity.}, } @article {pmid30047246, year = {2018}, author = {Zhao, T and Zhang, Y and Wu, H and Wang, D and Chen, Y and Zhu, MJ and Ma, LZ}, title = {Extracellular aminopeptidase modulates biofilm development of Pseudomonas aeruginosa by affecting matrix exopolysaccharide and bacterial cell death.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {583-593}, doi = {10.1111/1758-2229.12682}, pmid = {30047246}, issn = {1758-2229}, support = {/CA/NCI NIH HHS/United States ; }, abstract = {Biofilm bacteria are embedded within a self-secreted extracellular matrix that contains a considerable amount of proteins including many extracellular enzymes. However, little is known about the roles of such enzymes in biofilm development. Here, we studied Pseudomonas aeruginosa aminopeptidase (PaAP, encoded by PA2939 that we named the gene as paaP in this study), a quorum-sensing-regulated enzyme and one of the most abundant extracellular proteins in the biofilm matrix of this opportunistic pathogen and environmental bacterium. We found that deletion of paaP in P. aeruginosa increased initial attachment and biofilm formation at early stages of biofilm development. After 24 h growth, loss of PaAP resulted in substantial cell death and biofilm disruption. Bacterial cell death was independent of biofilm matrix polysaccharide Psl, while biofilm disruption was due to the degradation of Psl matrix by dead-bacteria-released glycosyl hydrolase PslG, thereby leading to biofilm dispersion. PaAP functioned extracellularly and aminopeptidase catalytic activity was essential for its effect on biofilm development. Our data reveal an important role of extracellular aminopeptidase in biofilm development, suggesting PaAP as a therapeutic target for preventing P. aeruginosa infection and combating biofilm-related complications.}, } @article {pmid30047196, year = {2018}, author = {Bennett, GM and Mao, M}, title = {Comparative genomics of a quadripartite symbiosis in a planthopper host reveals the origins and rearranged nutritional responsibilities of anciently diverged bacterial lineages.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4461-4472}, doi = {10.1111/1462-2920.14367}, pmid = {30047196}, issn = {1462-2920}, support = {IOS1347116//Division of Integrative Organismal Systems/ ; }, abstract = {Insects in the Auchenorrhyncha (Hemiptera: Suborder) established nutritional symbioses with bacteria approximately 300 million years ago (MYA). The suborder split early during its diversification (~ 250 MYA) into the Fulgoroidea (planthoppers) and Cicadomorpha (leafhoppers and cicadas). The two lineages share some symbionts, including Sulcia and possibly a Betaproteobacteria that collaboratively provide their hosts with 10 essential amino acids (EAA). Some hosts harbour three bacteria, as is common among planthoppers. However, genomic studies are currently restricted to the dual-bacterial symbioses found in Cicadomorpha, leaving the origins and functions of these more complex symbioses unclear. To address these questions, we sequenced the genomes and performed phylogenomic analyses of 'Candidatus Sulcia muelleri' (Bacteroidetes), 'Ca. Vidania fulgoroideae' (Betaproteobacteria) and 'Ca. Purcelliella pentastirinorum' (Gammaproteobacteria) from a planthopper (Cixiidae: Oliarus). In contrast to the Cicadomorpha, nutritional synthesis responsibilities are rearranged between the cixiid symbionts. Although Sulcia has a highly conserved genome across the Auchenorrhyncha, in the cixiids it is greatly reduced and provides only three EAAs. Vidania contributes the remaining seven EAAs. Phylogenomic results suggest that it represents an ancient symbiont lineage paired with Sulcia throughout the Auchenorrhyncha. Finally, Purcelliella was recently acquired from plant-insect associated bacteria (Pantoea-Erwinia) to provide B vitamins and metabolic support to its degenerate partners.}, } @article {pmid30047192, year = {2018}, author = {Whitman, T and Neurath, R and Perera, A and Chu-Jacoby, I and Ning, D and Zhou, J and Nico, P and Pett-Ridge, J and Firestone, M}, title = {Microbial community assembly differs across minerals in a rhizosphere microcosm.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4444-4460}, doi = {10.1111/1462-2920.14366}, pmid = {30047192}, issn = {1462-2920}, support = {DE-SC0010570//Biological and Environmental Research/ ; //University of California Hopland Research and Extension Center/ ; DE-AC52-07NA27344//Lawrence Livermore National Laboratory/ ; //U.S. Department of Energy/ ; //University of Oklahoma/ ; //UC Berkeley/ ; }, abstract = {Mineral-associated microbes drive many critical soil processes, including mineral weathering, soil aggregation and cycling of mineral-sorbed organic matter. To investigate the interactions between soil minerals and microbes in the rhizosphere, we incubated three types of minerals (ferrihydrite, kaolinite and quartz) and a native soil mineral fraction near roots of a common Californian annual grass, Avena barbata, growing in its resident soil. We followed microbial colonization of these minerals for up to 2.5 months - the plant's lifespan. Bacteria and fungi that colonized mineral surfaces during this experiment differed across mineral types and differed from those in the background soil, implying that microbial colonization was the result of processes in addition to passive movement with water to mineral surfaces. Null model analysis revealed that dispersal limitation was a dominant factor structuring mineral-associated microbial communities for all mineral types. Once bacteria arrived at a mineral surface, capacity for rapid growth appeared important, as ribosomal copy number was significantly correlated with relative enrichment on minerals. Glomeromycota (a phylum associated with arbuscular mycorrhizal fungi) appeared to preferentially associate with ferrihydrite surfaces. The mechanisms enabling the colonization of soil minerals may be foundational in shaping the overall soil microbiome composition and development of persistent organic matter in soils.}, } @article {pmid30047191, year = {2018}, author = {Ma, X and Coleman, ML and Waldbauer, JR}, title = {Distinct molecular signatures in dissolved organic matter produced by viral lysis of marine cyanobacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3001-3011}, doi = {10.1111/1462-2920.14338}, pmid = {30047191}, issn = {1462-2920}, support = {3305//Gordon and Betty Moore Foundation/ ; }, abstract = {Dissolved organic matter (DOM) plays a central role in the microbial ecology and biogeochemistry of aquatic environments, yet little is known about how the mechanism of DOM release from its ultimate source, primary producer biomass, affects the molecular composition of the inputs to the dissolved pool. Here we used a model marine phytoplankton, the picocyanobacterium Synechococcus WH7803, to compare the composition of DOM released by three mechanisms: exudation, mechanical cell lysis and infection by the lytic phage S-SM1. A broad, untargeted analytical approach reveals the complexity of this freshly sourced DOM, and comparative analysis between DOM produced by the different mechanisms suggests that exudation and viral lysis are sources of unsaturated, oxygen-rich and possibly novel biomolecules. Furthermore, viral lysis of WH7803 by S-SM1 releases abundant peptides derived from specific proteolysis of the major light-harvesting protein phycoerythrin, raising the possibility that phage infection of these abundant cyanobacteria could be a significant source of high molecular weight dissolved organic nitrogen compounds.}, } @article {pmid30047187, year = {2018}, author = {Janevska, S and Güldener, U and Sulyok, M and Tudzynski, B and Studt, L}, title = {Set1 and Kdm5 are antagonists for H3K4 methylation and regulators of the major conidiation-specific transcription factor gene ABA1 in Fusarium fujikuroi.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3343-3362}, pmid = {30047187}, issn = {1462-2920}, support = {M 2149-B22//Austrian Science Fund/ ; ME 1682/6-2TU101/16 2//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Here we present the identification and characterization of the H3K4-specific histone methyltransferase Set1 and its counterpart, the Jumonji C demethylase Kdm5, in the rice pathogen Fusarium fujikuroi. While Set1 is responsible for all detectable H3K4me2/me3 in this fungus, Kdm5 antagonizes the H3K4me3 mark. Notably, deletion of both SET1 and KDM5 mainly resulted in the upregulation of genome-wide transcription, also affecting a large set of secondary metabolite (SM) key genes. Although H3K4 methylation is a hallmark of actively transcribed euchromatin, several SM gene clusters located in subtelomeric regions were affected by Set1 and Kdm5. While the regulation of many of them is likely indirect, H3K4me2 levels at gibberellic acid (GA) genes correlated with GA biosynthesis in the wild type, Δkdm5 and OE::KDM5 under inducing conditions. Whereas Δset1 showed an abolished GA3 production in axenic culture, phytohormone biosynthesis was induced in planta, so that residual amounts of GA3 were detected during rice infection. Accordingly, Δset1 exhibited a strongly attenuated, though not abolished, virulence on rice. Apart from regulating secondary metabolism, Set1 and Kdm5 function as activator and repressor of conidiation respectively. They antagonistically regulate H3K4me3 levels and expression of the major conidiation-specific transcription factor gene ABA1 in F. fujikuroi.}, } @article {pmid30046636, year = {2018}, author = {Bird, SM and King, R}, title = {Multiple Systems Estimation (or Capture-Recapture Estimation) to Inform Public Policy.}, journal = {Annual review of statistics and its application}, volume = {5}, number = {}, pages = {95-118}, pmid = {30046636}, issn = {2326-8298}, support = {MC_U105260794//Medical Research Council/United Kingdom ; }, abstract = {Estimating population sizes has long been of interest, from the estimation of the human or ecological population size within regions or countries to the hidden number of civilian casualties in a war. Total enumeration of the population, for example, via a census, is often infeasible or simply impractical. However, a series of partial enumerations or observations of the population is often possible. This has led to the ideas of capture-recapture methods, which have been extensively used within ecology to estimate the size of wildlife populations, with an associated measure of uncertainty, and are most effectively applied when there are multiple capture occasions. Capture-recapture ideology can be more widely applied to multiple data-sources, by the linkage of individuals across the multiple lists. This is often referred to as Multiple Systems Estimation (MSE). The MSE approach has been preferred when estimating "capture-shy" or hard-to-reach populations, including those caught up in the criminal justice system; or homeless; or trafficked; or civilian casualties of war. Motivated by a range of public policy applications of MSE, each briefly introduced, we discuss practical problems with potentially substantial methodological implications. They include: "period" definition; "case" definition; when an observed count is not a true count of the population of interest but an upper bound due to mismatched definitions; exact or probabilistic matching of "cases" across different lists; demographic or other information about the "case" which may influence capture-propensities; required permissions to access extant-lists; list-creation by research-teams or interested parties; referrals (if presence on list A results - almost surely - in presence on list B); different mathematical models leading to widely different estimated population sizes; uncertainty in estimation; computational efficiency; external validation; hypothesis-generation; and additional independent external information. Returning to our motivational applications, we focus on whether the uncertainty which qualified their estimates was sufficiently narrow to orient public policy; and, if not, what options were available and/or taken to reduce the uncertainty or to seek external validation. We also consider whether MSE was hypothesis-generating: in the sense of having spawned new lines of inquiry.}, } @article {pmid30046236, year = {2018}, author = {Huang, H and Gao, H and Liu, B and Fan, M and Wang, J and Wang, C and Tian, H and Wang, L and Xie, C and Wu, D and Liu, L and Yan, J and Qi, T and Song, S}, title = {bHLH13 Regulates Jasmonate-Mediated Defense Responses and Growth.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318790265}, pmid = {30046236}, issn = {1176-9343}, abstract = {Jasmonates (JAs) regulate plant growth and defense responses. On perception of bioactive JAs, the JA receptor CORONATINE INSENSITIVE1 (COI1) recruits JA ZIM-domain (JAZ) proteins for degradation, and JAZ-targeted transcription factors are released to regulate JA responses. The subgroup IIId bHLH transcriptional factors, including bHLH17, bHLH13, bHLH3, and bHLH14, interact with JAZs and repress JA responses. In this study, we show that IIId bHLH factors form dimers via the C-terminus in yeast. N-terminus of bHLH13 is essential for its transcriptional repression function. bHLH13 overexpression inhibits Arabidopsis resistance to the necrotrophic fungi Botrytis cinerea and defense against the insect Spodoptera exigua. COI1 mutation disrupts the oversensitivity of the quadruple mutant bhlh3 bhlh13 bhlh14 bhlh17 in various JA responses, including anthocyanin accumulation, root growth inhibition, and defense against B cinerea and S exigua. Disruption of the TTG1/bHLH/MYB complex blocks anthocyanin accumulation of bhlh3 bhlh13 bhlh14 bhlh17, whereas abolishment of MYC2 attenuates JA-inhibitory root growth of bhlh3 bhlh13 bhlh14 bhlh17. These results genetically demonstrate that IIId bHLH factors function downstream of COI1 to inhibit distinctive JA responses via antagonizing different transcriptional activators.}, } @article {pmid30046176, year = {2018}, author = {}, title = {Deliver on diagnostics to save lives.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {847}, doi = {10.1038/s41564-018-0220-9}, pmid = {30046176}, issn = {2058-5276}, } @article {pmid30046175, year = {2018}, author = {de Goffau, MC and Lager, S and Salter, SJ and Wagner, J and Kronbichler, A and Charnock-Jones, DS and Peacock, SJ and Smith, GCS and Parkhill, J}, title = {Recognizing the reagent microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {851-853}, doi = {10.1038/s41564-018-0202-y}, pmid = {30046175}, issn = {2058-5276}, support = {MR/K021133/1//Medical Research Council/United Kingdom ; }, } @article {pmid30046174, year = {2018}, author = {Klassen, JL}, title = {Defining microbiome function.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {864-869}, doi = {10.1038/s41564-018-0189-4}, pmid = {30046174}, issn = {2058-5276}, abstract = {Why does a microorganism associate with a host? What function does it perform? Such questions are difficult to unequivocally address and remain hotly debated. This is partially because scientists often use different philosophical definitions of 'function' ambiguously and interchangeably, as exemplified by the controversy surrounding the Encyclopedia of DNA Elements (ENCODE) project. Here, I argue that research studying host-associated microbial communities and their genomes (that is, microbiomes) faces similar pitfalls and that unclear or misapplied conceptions of function underpin many controversies in this field. In particular, experiments that support phenomenological models of function can inappropriately be used to support functional models that instead require specific measurements of evolutionary selection. Microbiome research also requires uniquely clear definitions of 'who the function is for', in contrast to most single-organism systems where this is implicit. I illustrate how obscuring either of these issues can lead to substantial confusion and misinterpretation of microbiome function, using the varied conceptions of the holobiont as a current and cogent example. Using clear functional definitions and appropriate types of evidence are essential to effectively communicate microbiome research and foster host health.}, } @article {pmid30046173, year = {2018}, author = {Walsh, TR}, title = {A one-health approach to antimicrobial resistance.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {854-855}, doi = {10.1038/s41564-018-0208-5}, pmid = {30046173}, issn = {2058-5276}, } @article {pmid30046172, year = {2018}, author = {Potrykus, K and Cashel, M}, title = {Growth at best and worst of times.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {862-863}, doi = {10.1038/s41564-018-0207-6}, pmid = {30046172}, issn = {2058-5276}, } @article {pmid30046171, year = {2018}, author = {Spoto, M and Oh, J}, title = {Resident risks.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {858-859}, doi = {10.1038/s41564-018-0212-9}, pmid = {30046171}, issn = {2058-5276}, } @article {pmid30046170, year = {2018}, author = {Carrington, M and Higgins, MK}, title = {O-h what a surprise.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {856-857}, doi = {10.1038/s41564-018-0211-x}, pmid = {30046170}, issn = {2058-5276}, } @article {pmid30046169, year = {2018}, author = {Horby, P}, title = {Improving preparedness for the next flu pandemic.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {848-850}, doi = {10.1038/s41564-018-0206-7}, pmid = {30046169}, issn = {2058-5276}, } @article {pmid30046168, year = {2018}, author = {Brunke, S and Hube, B}, title = {The needle and the damage done.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {860-861}, doi = {10.1038/s41564-018-0194-7}, pmid = {30046168}, issn = {2058-5276}, } @article {pmid30046114, year = {2018}, author = {Landig, AJ and Koski, JV and Scarlino, P and Mendes, UC and Blais, A and Reichl, C and Wegscheider, W and Wallraff, A and Ensslin, K and Ihn, T}, title = {Coherent spin-photon coupling using a resonant exchange qubit.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {179-184}, doi = {10.1038/s41586-018-0365-y}, pmid = {30046114}, issn = {1476-4687}, abstract = {Electron spins hold great promise for quantum computation because of their long coherence times. Long-distance coherent coupling of spins is a crucial step towards quantum information processing with spin qubits. One approach to realizing interactions between distant spin qubits is to use photons as carriers of quantum information. Here we demonstrate strong coupling between single microwave photons in a niobium titanium nitride high-impedance resonator and a three-electron spin qubit (also known as a resonant exchange qubit) in a gallium arsenide device consisting of three quantum dots. We observe the vacuum Rabi mode splitting of the resonance of the resonator, which is a signature of strong coupling; specifically, we observe a coherent coupling strength of about 31 megahertz and a qubit decoherence rate of about 20 megahertz. We can tune the decoherence electrostatically to obtain a minimal decoherence rate of around 10 megahertz for a coupling strength of around 23 megahertz. We directly measure the dependence of the qubit-photon coupling strength on the tunable electric dipole moment of the qubit using the 'AC Stark' effect. Our demonstration of strong qubit-photon coupling for a three-electron spin qubit is an important step towards coherent long-distance coupling of spin qubits.}, } @article {pmid30046113, year = {2018}, author = {Dhir, A and Dhir, S and Borowski, LS and Jimenez, L and Teitell, M and Rötig, A and Crow, YJ and Rice, GI and Duffy, D and Tamby, C and Nojima, T and Munnich, A and Schiff, M and de Almeida, CR and Rehwinkel, J and Dziembowski, A and Szczesny, RJ and Proudfoot, NJ}, title = {Mitochondrial double-stranded RNA triggers antiviral signalling in humans.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {238-242}, doi = {10.1038/s41586-018-0363-0}, pmid = {30046113}, issn = {1476-4687}, support = {107928/Z/15/Z//Wellcome Trust/United Kingdom ; GM073981/GM/NIGMS NIH HHS/United States ; }, abstract = {Mitochondria are descendants of endosymbiotic bacteria and retain essential prokaryotic features such as a compact circular genome. Consequently, in mammals, mitochondrial DNA is subjected to bidirectional transcription that generates overlapping transcripts, which are capable of forming long double-stranded RNA structures1,2. However, to our knowledge, mitochondrial double-stranded RNA has not been previously characterized in vivo. Here we describe the presence of a highly unstable native mitochondrial double-stranded RNA species at single-cell level and identify key roles for the degradosome components mitochondrial RNA helicase SUV3 and polynucleotide phosphorylase PNPase in restricting the levels of mitochondrial double-stranded RNA. Loss of either enzyme results in massive accumulation of mitochondrial double-stranded RNA that escapes into the cytoplasm in a PNPase-dependent manner. This process engages an MDA5-driven antiviral signalling pathway that triggers a type I interferon response. Consistent with these data, patients carrying hypomorphic mutations in the gene PNPT1, which encodes PNPase, display mitochondrial double-stranded RNA accumulation coupled with upregulation of interferon-stimulated genes and other markers of immune activation. The localization of PNPase to the mitochondrial inter-membrane space and matrix suggests that it has a dual role in preventing the formation and release of mitochondrial double-stranded RNA into the cytoplasm. This in turn prevents the activation of potent innate immune defence mechanisms that have evolved to protect vertebrates against microbial and viral attack.}, } @article {pmid30046112, year = {2018}, author = {Zhong, Z and Liang, S and Sanchez-Lopez, E and He, F and Shalapour, S and Lin, XJ and Wong, J and Ding, S and Seki, E and Schnabl, B and Hevener, AL and Greenberg, HB and Kisseleva, T and Karin, M}, title = {New mitochondrial DNA synthesis enables NLRP3 inflammasome activation.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {198-203}, doi = {10.1038/s41586-018-0372-z}, pmid = {30046112}, issn = {1476-4687}, support = {R01 AA020172/AA/NIAAA NIH HHS/United States ; P42 ES010337/ES/NIEHS NIH HHS/United States ; R01 DK085252/DK/NIDDK NIH HHS/United States ; R01 DK111866/DK/NIDDK NIH HHS/United States ; R01 DK099205/DK/NIDDK NIH HHS/United States ; U01 AA022614/AA/NIAAA NIH HHS/United States ; R01 CA163798/CA/NCI NIH HHS/United States ; R01 AI043477/AI/NIAID NIH HHS/United States ; R01 DK101737/DK/NIDDK NIH HHS/United States ; }, abstract = {Dysregulated NLRP3 inflammasome activity results in uncontrolled inflammation, which underlies many chronic diseases. Although mitochondrial damage is needed for the assembly and activation of the NLRP3 inflammasome, it is unclear how macrophages are able to respond to structurally diverse inflammasome-activating stimuli. Here we show that the synthesis of mitochondrial DNA (mtDNA), induced after the engagement of Toll-like receptors, is crucial for NLRP3 signalling. Toll-like receptors signal via the MyD88 and TRIF adaptors to trigger IRF1-dependent transcription of CMPK2, a rate-limiting enzyme that supplies deoxyribonucleotides for mtDNA synthesis. CMPK2-dependent mtDNA synthesis is necessary for the production of oxidized mtDNA fragments after exposure to NLRP3 activators. Cytosolic oxidized mtDNA associates with the NLRP3 inflammasome complex and is required for its activation. The dependence on CMPK2 catalytic activity provides opportunities for more effective control of NLRP3 inflammasome-associated diseases.}, } @article {pmid30046111, year = {2018}, author = {Da Mesquita, S and Louveau, A and Vaccari, A and Smirnov, I and Cornelison, RC and Kingsmore, KM and Contarino, C and Onengut-Gumuscu, S and Farber, E and Raper, D and Viar, KE and Powell, RD and Baker, W and Dabhi, N and Bai, R and Cao, R and Hu, S and Rich, SS and Munson, JM and Lopes, MB and Overall, CC and Acton, ST and Kipnis, J}, title = {Functional aspects of meningeal lymphatics in ageing and Alzheimer's disease.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {185-191}, pmid = {30046111}, issn = {1476-4687}, support = {R01 AG034113/AG/NIA NIH HHS/United States ; R01 CA222563/CA/NCI NIH HHS/United States ; R37 CA222563/CA/NCI NIH HHS/United States ; RF1 AG057496/AG/NIA NIH HHS/United States ; }, abstract = {Ageing is a major risk factor for many neurological pathologies, but its mechanisms remain unclear. Unlike other tissues, the parenchyma of the central nervous system (CNS) lacks lymphatic vasculature and waste products are removed partly through a paravascular route. (Re)discovery and characterization of meningeal lymphatic vessels has prompted an assessment of their role in waste clearance from the CNS. Here we show that meningeal lymphatic vessels drain macromolecules from the CNS (cerebrospinal and interstitial fluids) into the cervical lymph nodes in mice. Impairment of meningeal lymphatic function slows paravascular influx of macromolecules into the brain and efflux of macromolecules from the interstitial fluid, and induces cognitive impairment in mice. Treatment of aged mice with vascular endothelial growth factor C enhances meningeal lymphatic drainage of macromolecules from the cerebrospinal fluid, improving brain perfusion and learning and memory performance. Disruption of meningeal lymphatic vessels in transgenic mouse models of Alzheimer's disease promotes amyloid-β deposition in the meninges, which resembles human meningeal pathology, and aggravates parenchymal amyloid-β accumulation. Meningeal lymphatic dysfunction may be an aggravating factor in Alzheimer's disease pathology and in age-associated cognitive decline. Thus, augmentation of meningeal lymphatic function might be a promising therapeutic target for preventing or delaying age-associated neurological diseases.}, } @article {pmid30046110, year = {2018}, author = {Ghezraoui, H and Oliveira, C and Becker, JR and Bilham, K and Moralli, D and Anzilotti, C and Fischer, R and Deobagkar-Lele, M and Sanchiz-Calvo, M and Fueyo-Marcos, E and Bonham, S and Kessler, BM and Rottenberg, S and Cornall, RJ and Green, CM and Chapman, JR}, title = {53BP1 cooperation with the REV7-shieldin complex underpins DNA structure-specific NHEJ.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {122-127}, doi = {10.1038/s41586-018-0362-1}, pmid = {30046110}, issn = {1476-4687}, support = {MR/M009971/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cell Line ; DNA/*chemistry/*metabolism ; DNA Breaks, Double-Stranded ; *DNA End-Joining Repair ; DNA, Single-Stranded/chemistry/metabolism ; Female ; Humans ; Immunoglobulin Class Switching/genetics ; Mad2 Proteins/deficiency/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Multiprotein Complexes/chemistry/*metabolism ; Mutation ; Tumor Suppressor p53-Binding Protein 1/deficiency/*metabolism ; V(D)J Recombination/genetics ; }, abstract = {53BP1 governs a specialized, context-specific branch of the classical non-homologous end joining DNA double-strand break repair pathway. Mice lacking 53bp1 (also known as Trp53bp1) are immunodeficient owing to a complete loss of immunoglobulin class-switch recombination1,2, and reduced fidelity of long-range V(D)J recombination3. The 53BP1-dependent pathway is also responsible for pathological joining events at dysfunctional telomeres4, and its unrestricted activity in Brca1-deficient cellular and tumour models causes genomic instability and oncogenesis5-7. Cells that lack core non-homologous end joining proteins are profoundly radiosensitive8, unlike 53BP1-deficient cells9,10, which suggests that 53BP1 and its co-factors act on specific DNA substrates. Here we show that 53BP1 cooperates with its downstream effector protein REV7 to promote non-homologous end joining during class-switch recombination, but REV7 is not required for 53BP1-dependent V(D)J recombination. We identify shieldin-a four-subunit putative single-stranded DNA-binding complex comprising REV7, c20orf196 (SHLD1), FAM35A (SHLD2) and FLJ26957 (SHLD3)-as the factor that explains this specificity. Shieldin is essential for REV7-dependent DNA end-protection and non-homologous end joining during class-switch recombination, and supports toxic non-homologous end joining in Brca1-deficient cells, yet is dispensable for REV7-dependent interstrand cross-link repair. The 53BP1 pathway therefore comprises distinct double-strand break repair activities within chromatin and single-stranded DNA compartments, which explains both the immunological differences between 53bp1- and Rev7- deficient mice and the context specificity of the pathway.}, } @article {pmid30046109, year = {2018}, author = {Hubler, Z and Allimuthu, D and Bederman, I and Elitt, MS and Madhavan, M and Allan, KC and Shick, HE and Garrison, E and T Karl, M and Factor, DC and Nevin, ZS and Sax, JL and Thompson, MA and Fedorov, Y and Jin, J and Wilson, WK and Giera, M and Bracher, F and Miller, RH and Tesar, PJ and Adams, DJ}, title = {Accumulation of 8,9-unsaturated sterols drives oligodendrocyte formation and remyelination.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {372-376}, doi = {10.1038/s41586-018-0360-3}, pmid = {30046109}, issn = {1476-4687}, support = {R01 NS095280/NS/NINDS NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; P30 CA043703/CA/NCI NIH HHS/United States ; }, abstract = {Regeneration of myelin is mediated by oligodendrocyte progenitor cells-an abundant stem cell population in the central nervous system (CNS) and the principal source of new myelinating oligodendrocytes. Loss of myelin-producing oligodendrocytes in the CNS underlies a number of neurological diseases, including multiple sclerosis and diverse genetic diseases1-3. High-throughput chemical screening approaches have been used to identify small molecules that stimulate the formation of oligodendrocytes from oligodendrocyte progenitor cells and functionally enhance remyelination in vivo4-10. Here we show that a wide range of these pro-myelinating small molecules function not through their canonical targets but by directly inhibiting CYP51, TM7SF2, or EBP, a narrow range of enzymes within the cholesterol biosynthesis pathway. Subsequent accumulation of the 8,9-unsaturated sterol substrates of these enzymes is a key mechanistic node that promotes oligodendrocyte formation, as 8,9-unsaturated sterols are effective when supplied to oligodendrocyte progenitor cells in purified form whereas analogous sterols that lack this structural feature have no effect. Collectively, our results define a unifying sterol-based mechanism of action for most known small-molecule enhancers of oligodendrocyte formation and highlight specific targets to propel the development of optimal remyelinating therapeutics.}, } @article {pmid30046108, year = {2018}, author = {Stuart-Smith, RD and Brown, CJ and Ceccarelli, DM and Edgar, GJ}, title = {Ecosystem restructuring along the Great Barrier Reef following mass coral bleaching.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {92-96}, doi = {10.1038/s41586-018-0359-9}, pmid = {30046108}, issn = {1476-4687}, mesh = {Animals ; Anthozoa/*physiology ; Aquatic Organisms/classification/isolation & purification/*physiology ; *Biodiversity ; *Coral Reefs ; Fishes/physiology ; *Global Warming ; Oceans and Seas ; Population Dynamics ; Seawater/analysis ; Temperature ; }, abstract = {Global warming is markedly changing diverse coral reef ecosystems through an increasing frequency and magnitude of mass bleaching events1-3. How local impacts scale up across affected regions depends on numerous factors, including patchiness in coral mortality, metabolic effects of extreme temperatures on populations of reef-dwelling species4 and interactions between taxa. Here we use data from before and after the 2016 mass bleaching event to evaluate ecological changes in corals, algae, fishes and mobile invertebrates at 186 sites along the full latitudinal span of the Great Barrier Reef and western Coral Sea. One year after the bleaching event, reductions in live coral cover of up to 51% were observed on surveyed reefs that experienced extreme temperatures; however, regional patterns of coral mortality were patchy. Consistent declines in coral-feeding fishes were evident at the most heavily affected reefs, whereas few other short-term responses of reef fishes and invertebrates could be attributed directly to changes in coral cover. Nevertheless, substantial region-wide ecological changes occurred that were mostly independent of coral loss, and instead appeared to be linked directly to sea temperatures. Community-wide trophic restructuring was evident, with weakening of strong pre-existing latitudinal gradients in the diversity of fishes, invertebrates and their functional groups. In particular, fishes that scrape algae from reef surfaces, which are considered to be important for recovery after bleaching2, declined on northern reefs, whereas other herbivorous groups increased on southern reefs. The full impact of the 2016 bleaching event may not be realized until dead corals erode during the next decade5,6. However, our short-term observations suggest that the recovery processes, and the ultimate scale of impact, are affected by functional changes in communities, which in turn depend on the thermal affinities of local reef-associated fauna. Such changes will vary geographically, and may be particularly acute at locations where many fishes and invertebrates are close to their thermal distribution limits7.}, } @article {pmid30046107, year = {2018}, author = {Unuchek, D and Ciarrocchi, A and Avsar, A and Watanabe, K and Taniguchi, T and Kis, A}, title = {Room-temperature electrical control of exciton flux in a van der Waals heterostructure.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {340-344}, doi = {10.1038/s41586-018-0357-y}, pmid = {30046107}, issn = {1476-4687}, abstract = {Devices that rely on the manipulation of excitons-bound pairs of electrons and holes-hold great promise for realizing efficient interconnects between optical data transmission and electrical processing systems. Although exciton-based transistor actions have been demonstrated successfully in bulk semiconductor-based coupled quantum wells1-3, the low temperature required for their operation limits their practical application. The recent emergence of two-dimensional semiconductors with large exciton binding energies4,5 may lead to excitonic devices and circuits that operate at room temperature. Whereas individual two-dimensional materials have short exciton diffusion lengths, the spatial separation of electrons and holes in different layers in heterostructures could help to overcome this limitation and enable room-temperature operation of mesoscale devices6-8. Here we report excitonic devices made of MoS2-WSe2 van der Waals heterostructures encapsulated in hexagonal boron nitride that demonstrate electrically controlled transistor actions at room temperature. The long-lived nature of the interlayer excitons in our device results in them diffusing over a distance of five micrometres. Within our device, we further demonstrate the ability to manipulate exciton dynamics by creating electrically reconfigurable confining and repulsive potentials for the exciton flux. Our results make a strong case for integrating two-dimensional materials in future excitonic devices to enable operation at room temperature.}, } @article {pmid30046106, year = {2018}, author = {Wilson, DE and Scholl, B and Fitzpatrick, D}, title = {Differential tuning of excitation and inhibition shapes direction selectivity in ferret visual cortex.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {97-101}, doi = {10.1038/s41586-018-0354-1}, pmid = {30046106}, issn = {1476-4687}, mesh = {Animals ; Attentional Bias/*physiology ; Excitatory Postsynaptic Potentials/*physiology ; Female ; Ferrets/*physiology ; GABAergic Neurons/physiology ; Inhibitory Postsynaptic Potentials/physiology ; Interneurons/physiology ; *Motion ; Neural Inhibition/*physiology ; Synapses/metabolism ; Visual Cortex/anatomy & histology/*cytology/*physiology ; }, abstract = {To encode specific sensory inputs, cortical neurons must generate selective responses for distinct stimulus features. In principle, a variety of factors can contribute to the response selectivity of a cortical neuron: the tuning and strength of excitatory1-3 and inhibitory synaptic inputs4-6, dendritic nonlinearities7-9 and spike threshold10,11. Here we use a combination of techniques including in vivo whole-cell recording, synaptic- and cellular-resolution in vivo two-photon calcium imaging, and GABA (γ-aminobutyric acid) neuron-selective optogenetic manipulation to dissect the factors that contribute to the direction-selective responses of layer 2/3 neurons in ferret visual cortex (V1). Two-photon calcium imaging of dendritic spines12,13 revealed that each neuron receives a mixture of excitatory synaptic inputs selective for the somatic preferred or null direction of motion. The relative number of preferred- and null-tuned excitatory inputs predicted a neuron's somatic direction preference, but failed to account for the degree of direction selectivity. By contrast, in vivo whole-cell patch-clamp recordings revealed a notable degree of direction selectivity in subthreshold responses that was significantly correlated with spiking direction selectivity. Subthreshold direction selectivity was predicted by the magnitude and variance of the response to the null direction of motion, and several lines of evidence, including conductance measurements, demonstrate that differential tuning of excitation and inhibition suppresses responses to the null direction of motion. Consistent with this idea, optogenetic inactivation of GABAergic neurons in layer 2/3 reduced direction selectivity by enhancing responses to the null direction. Furthermore, by optogenetically mapping connections of inhibitory neurons in layer 2/3 in vivo, we find that layer 2/3 inhibitory neurons make long-range, intercolumnar projections to excitatory neurons that prefer the opposite direction of motion. We conclude that intracortical inhibition exerts a major influence on the degree of direction selectivity in layer 2/3 of ferret V1 by suppressing responses to the null direction of motion.}, } @article {pmid30046105, year = {2018}, author = {Wyllie, S and Thomas, M and Patterson, S and Crouch, S and De Rycker, M and Lowe, R and Gresham, S and Urbaniak, MD and Otto, TD and Stojanovski, L and Simeons, FRC and Manthri, S and MacLean, LM and Zuccotto, F and Homeyer, N and Pflaumer, H and Boesche, M and Sastry, L and Connolly, P and Albrecht, S and Berriman, M and Drewes, G and Gray, DW and Ghidelli-Disse, S and Dixon, S and Fiandor, JM and Wyatt, PG and Ferguson, MAJ and Fairlamb, AH and Miles, TJ and Read, KD and Gilbert, IH}, title = {Cyclin-dependent kinase 12 is a drug target for visceral leishmaniasis.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {192-197}, doi = {10.1038/s41586-018-0356-z}, pmid = {30046105}, issn = {1476-4687}, support = {092340//Wellcome Trust/United Kingdom ; 105021//Wellcome Trust/United Kingdom ; 100476//Wellcome Trust/United Kingdom ; 101842//Wellcome Trust/United Kingdom ; 079838//Wellcome Trust/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; }, abstract = {Visceral leishmaniasis causes considerable mortality and morbidity in many parts of the world. There is an urgent need for the development of new, effective treatments for this disease. Here we describe the development of an anti-leishmanial drug-like chemical series based on a pyrazolopyrimidine scaffold. The leading compound from this series (7, DDD853651/GSK3186899) is efficacious in a mouse model of visceral leishmaniasis, has suitable physicochemical, pharmacokinetic and toxicological properties for further development, and has been declared a preclinical candidate. Detailed mode-of-action studies indicate that compounds from this series act principally by inhibiting the parasite cdc-2-related kinase 12 (CRK12), thus defining a druggable target for visceral leishmaniasis.}, } @article {pmid30046104, year = {2018}, author = {Donihue, CM and Herrel, A and Fabre, AC and Kamath, A and Geneva, AJ and Schoener, TW and Kolbe, JJ and Losos, JB}, title = {Hurricane-induced selection on the morphology of an island lizard.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {88-91}, doi = {10.1038/s41586-018-0352-3}, pmid = {30046104}, issn = {1476-4687}, mesh = {Animals ; Body Size ; *Cyclonic Storms ; *Disasters ; Extremities/anatomy & histology ; Female ; Femur/anatomy & histology ; Humerus/anatomy & histology ; Islands ; Lizards/*anatomy & histology ; Male ; *Selection, Genetic ; West Indies ; }, abstract = {Hurricanes are catastrophically destructive. Beyond their toll on human life and livelihoods, hurricanes have tremendous and often long-lasting effects on ecological systems1,2. Despite many examples of mass mortality events following hurricanes3-5, hurricane-induced natural selection has not previously been demonstrated. Immediately after we finished a survey of Anolis scriptus-a common, small-bodied lizard found throughout the Turks and Caicos archipelago-our study populations were battered by Hurricanes Irma and Maria. Shortly thereafter, we revisited the populations to determine whether morphological traits related to clinging capacity had shifted in the intervening six weeks and found that populations of surviving lizards differed in body size, relative limb length and toepad size from those present before the storm. Our serendipitous study, which to our knowledge is the first to use an immediately before and after comparison6 to investigate selection caused by hurricanes, demonstrates that hurricanes can induce phenotypic change in a population and strongly implicates natural selection as the cause. In the decades ahead, as extreme climate events are predicted to become more intense and prevalent7,8, our understanding of evolutionary dynamics needs to incorporate the effects of these potentially severe selective episodes9-11.}, } @article {pmid30046103, year = {2018}, author = {Raj, L and Ide, T and Gurkar, AU and Foley, M and Schenone, M and Li, X and Tolliday, NJ and Golub, TR and Carr, SA and Shamji, AF and Stern, AM and Mandinova, A and Schreiber, SL and Lee, SW}, title = {Retraction Note: Selective killing of cancer cells by a small molecule targeting the stress response to ROS.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {420}, pmid = {30046103}, issn = {1476-4687}, abstract = {This Letter is being retracted owing to issues with Fig. 1d and Supplementary Fig. 31b, and the unavailability of original data for these figures that raise concerns regarding the integrity of the figures. Nature published two previous corrections related to this Letter1,2. These issues in aggregate undermine the confidence in the integrity of this study. Authors Michael Foley, Monica Schenone, Nicola J. Tolliday, Todd R. Golub, Steven A. Carr, Alykhan F. Shamji, Andrew M. Stern and Stuart L. Schreiber agree with the Retraction. Authors Lakshmi Raj, Takao Ide, Aditi U. Gurkar, Anna Mandinova and Sam W. Lee disagree with the Retraction. Author Xiaoyu Li did not respond.}, } @article {pmid30046102, year = {2018}, author = {Iaccarino, HF and Singer, AC and Martorell, AJ and Rudenko, A and Gao, F and Gillingham, TZ and Mathys, H and Seo, J and Kritskiy, O and Abdurrob, F and Adaikkan, C and Canter, RG and Rueda, R and Brown, EN and Boyden, ES and Tsai, LH}, title = {Author Correction: Gamma frequency entrainment attenuates amyloid load and modifies microglia.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {E1}, doi = {10.1038/s41586-018-0351-4}, pmid = {30046102}, issn = {1476-4687}, abstract = {Change history: In this Article, Extended Data Fig. 8 and Extended Data Table 1 contained errors, which have been corrected online.}, } @article {pmid30046090, year = {2018}, author = {Maxmen, A}, title = {How to defuse malaria's ticking time bomb.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {458-465}, doi = {10.1038/d41586-018-05772-z}, pmid = {30046090}, issn = {1476-4687}, mesh = {Animals ; Armed Conflicts ; Artemisinins/therapeutic use ; Cambodia/epidemiology ; Culicidae/parasitology ; Drug Resistance ; Female ; Foundations/economics ; *Global Health/economics ; Humans ; Malaria/diagnosis/*epidemiology/parasitology/*prevention & control ; Male ; Myanmar/epidemiology ; Plasmodium falciparum/drug effects/genetics/isolation & purification ; }, } @article {pmid30046088, year = {2018}, author = {}, title = {Fruit-fly brain, the real Lorax and new geological ages.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {448-449}, doi = {10.1038/d41586-018-05775-w}, pmid = {30046088}, issn = {1476-4687}, } @article {pmid30046087, year = {2018}, author = {Turcheniuk, K and Bondarev, D and Singhal, V and Yushin, G}, title = {Ten years left to redesign lithium-ion batteries.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {467-470}, doi = {10.1038/d41586-018-05752-3}, pmid = {30046087}, issn = {1476-4687}, } @article {pmid30046086, year = {2018}, author = {Moses, L and Niemi, S and Karlsson, E}, title = {Pet genomics medicine runs wild.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {470-472}, doi = {10.1038/d41586-018-05771-0}, pmid = {30046086}, issn = {1476-4687}, mesh = {Animals ; Cat Diseases/diagnosis/epidemiology/genetics/prevention & control ; Cats ; Conflict of Interest ; Dog Diseases/*diagnosis/epidemiology/*genetics/prevention & control ; Dogs ; Genetic Counseling ; Genetic Testing/*legislation & jurisprudence/*veterinary ; Genomics/*legislation & jurisprudence ; Guidelines as Topic ; Humans ; Legislation, Veterinary ; Pets/*genetics ; Reproducibility of Results ; Sensitivity and Specificity ; *Uncertainty ; Veterinary Medicine ; }, } @article {pmid30046085, year = {2018}, author = {Drew, L}, title = {An age-old story of dementia.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S2-S3}, doi = {10.1038/d41586-018-05718-5}, pmid = {30046085}, issn = {1476-4687}, } @article {pmid30046084, year = {2018}, author = {Sohn, E}, title = {How the evidence stacks up for preventing Alzheimer's disease.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S18-S20}, doi = {10.1038/d41586-018-05724-7}, pmid = {30046084}, issn = {1476-4687}, } @article {pmid30046083, year = {2018}, author = {King, A}, title = {The search for better animal models of Alzheimer's disease.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S13-S15}, doi = {10.1038/d41586-018-05722-9}, pmid = {30046083}, issn = {1476-4687}, } @article {pmid30046082, year = {2018}, author = {Costandi, M}, title = {Ways to stop the spread of Alzheimer's disease.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S16-S17}, doi = {10.1038/d41586-018-05723-8}, pmid = {30046082}, issn = {1476-4687}, } @article {pmid30046081, year = {2018}, author = {Dolgin, E}, title = {Alzheimer's disease is getting easier to spot.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S10-S12}, doi = {10.1038/d41586-018-05721-w}, pmid = {30046081}, issn = {1476-4687}, } @article {pmid30046080, year = {2018}, author = {Makin, S}, title = {The amyloid hypothesis on trial.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S4-S7}, doi = {10.1038/d41586-018-05719-4}, pmid = {30046080}, issn = {1476-4687}, } @article {pmid30046079, year = {2018}, author = {Gravitz, L}, title = {Drawing on the brain's resilience to fight Alzheimer's disease.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S8-S9}, doi = {10.1038/d41586-018-05720-x}, pmid = {30046079}, issn = {1476-4687}, } @article {pmid30046078, year = {2018}, author = {Hodson, R}, title = {Alzheimer's disease.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {S1}, doi = {10.1038/d41586-018-05717-6}, pmid = {30046078}, issn = {1476-4687}, } @article {pmid30046077, year = {2018}, author = {Krinner, L and Stewart, M and Pazmiño, A and Kwon, J and Schneble, D}, title = {Spontaneous emission of matter waves from a tunable open quantum system.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {589-592}, doi = {10.1038/s41586-018-0348-z}, pmid = {30046077}, issn = {1476-4687}, abstract = {The decay of an excited atom undergoing spontaneous photon emission into the fluctuating quantum-electrodynamic vacuum is an emblematic example of the dynamics of an open quantum system. Recent experiments have demonstrated that the gapped photon dispersion in periodic structures, which prevents photons in certain frequency ranges from propagating, can give rise to unusual spontaneous-decay behaviour, including the formation of dissipative bound states1-3. So far, these effects have been restricted to the optical domain. Here we demonstrate similar behaviour in a system of artificial emitters, realized using ultracold atoms in an optical lattice, which decay by emitting matter-wave, rather than optical, radiation into free space. By controlling vacuum coupling and the excitation energy, we directly observe exponential and partly reversible non-Markovian dynamics and detect a tunable bound state that contains evanescent matter waves. Our system provides a flexible platform for simulating open-system quantum electrodynamics and for studying dissipative many-body physics with ultracold atoms4-6.}, } @article {pmid30046076, year = {2018}, author = {Yokoyama, Y and Esat, TM and Thompson, WG and Thomas, AL and Webster, JM and Miyairi, Y and Sawada, C and Aze, T and Matsuzaki, H and Okuno, J and Fallon, S and Braga, JC and Humblet, M and Iryu, Y and Potts, DC and Fujita, K and Suzuki, A and Kan, H}, title = {Rapid glaciation and a two-step sea level plunge into the Last Glacial Maximum.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {603-607}, doi = {10.1038/s41586-018-0335-4}, pmid = {30046076}, issn = {1476-4687}, mesh = {Animals ; Anthozoa ; Coral Reefs ; Foraminifera ; History, Ancient ; Ice Cover/*chemistry ; Rhodophyta ; Seawater/*analysis/*chemistry ; }, abstract = {The approximately 10,000-year-long Last Glacial Maximum, before the termination of the last ice age, was the coldest period in Earth's recent climate history1. Relative to the Holocene epoch, atmospheric carbon dioxide was about 100 parts per million lower and tropical sea surface temperatures were about 3 to 5 degrees Celsius lower2,3. The Last Glacial Maximum began when global mean sea level (GMSL) abruptly dropped by about 40 metres around 31,000 years ago4 and was followed by about 10,000 years of rapid deglaciation into the Holocene1. The masses of the melting polar ice sheets and the change in ocean volume, and hence in GMSL, are primary constraints for climate models constructed to describe the transition between the Last Glacial Maximum and the Holocene, and future changes; but the rate, timing and magnitude of this transition remain uncertain. Here we show that sea level at the shelf edge of the Great Barrier Reef dropped by around 20 metres between 21,900 and 20,500 years ago, to -118 metres relative to the modern level. Our findings are based on recovered and radiometrically dated fossil corals and coralline algae assemblages, and represent relative sea level at the Great Barrier Reef, rather than GMSL. Subsequently, relative sea level rose at a rate of about 3.5 millimetres per year for around 4,000 years. The rise is consistent with the warming previously observed at 19,000 years ago1,5, but we now show that it occurred just after the 20-metre drop in relative sea level and the related increase in global ice volumes. The detailed structure of our record is robust because the Great Barrier Reef is remote from former ice sheets and tectonic activity. Relative sea level can be influenced by Earth's response to regional changes in ice and water loadings and may differ greatly from GMSL. Consequently, we used glacio-isostatic models to derive GMSL, and find that the Last Glacial Maximum culminated 20,500 years ago in a GMSL low of about -125 to -130 metres.}, } @article {pmid30046075, year = {2018}, author = {Barlow, J and França, F and Gardner, TA and Hicks, CC and Lennox, GD and Berenguer, E and Castello, L and Economo, EP and Ferreira, J and Guénard, B and Gontijo Leal, C and Isaac, V and Lees, AC and Parr, CL and Wilson, SK and Young, PJ and Graham, NAJ}, title = {The future of hyperdiverse tropical ecosystems.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {517-526}, doi = {10.1038/s41586-018-0301-1}, pmid = {30046075}, issn = {1476-4687}, mesh = {Animals ; *Biodiversity ; Climate Change ; Conservation of Natural Resources/*trends ; Human Activities ; Plants ; Socioeconomic Factors ; *Tropical Climate ; }, abstract = {The tropics contain the overwhelming majority of Earth's biodiversity: their terrestrial, freshwater and marine ecosystems hold more than three-quarters of all species, including almost all shallow-water corals and over 90% of terrestrial birds. However, tropical ecosystems are also subject to pervasive and interacting stressors, such as deforestation, overfishing and climate change, and they are set within a socio-economic context that includes growing pressure from an increasingly globalized world, larger and more affluent tropical populations, and weak governance and response capacities. Concerted local, national and international actions are urgently required to prevent a collapse of tropical biodiversity.}, } @article {pmid30046074, year = {2018}, author = {Griffith, KJ and Wiaderek, KM and Cibin, G and Marbella, LE and Grey, CP}, title = {Niobium tungsten oxides for high-rate lithium-ion energy storage.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {556-563}, doi = {10.1038/s41586-018-0347-0}, pmid = {30046074}, issn = {1476-4687}, abstract = {The maximum power output and minimum charging time of a lithium-ion battery depend on both ionic and electronic transport. Ionic diffusion within the electrochemically active particles generally represents a fundamental limitation to the rate at which a battery can be charged and discharged. To compensate for the relatively slow solid-state ionic diffusion and to enable high power and rapid charging, the active particles are frequently reduced to nanometre dimensions, to the detriment of volumetric packing density, cost, stability and sustainability. As an alternative to nanoscaling, here we show that two complex niobium tungsten oxides-Nb16W5O55 and Nb18W16O93, which adopt crystallographic shear and bronze-like structures, respectively-can intercalate large quantities of lithium at high rates, even when the sizes of the niobium tungsten oxide particles are of the order of micrometres. Measurements of lithium-ion diffusion coefficients in both structures reveal room-temperature values that are several orders of magnitude higher than those in typical electrode materials such as Li4Ti5O12 and LiMn2O4. Multielectron redox, buffered volume expansion, topologically frustrated niobium/tungsten polyhedral arrangements and rapid solid-state lithium transport lead to extremely high volumetric capacities and rate performance. Unconventional materials and mechanisms that enable lithiation of micrometre-sized particles in minutes have implications for high-power applications, fast-charging devices, all-solid-state energy storage systems, electrode design and material discovery.}, } @article {pmid30046073, year = {2018}, author = {De Rycker, M and Baragaña, B and Duce, SL and Gilbert, IH}, title = {Challenges and recent progress in drug discovery for tropical diseases.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {498-506}, pmid = {30046073}, issn = {1476-4687}, support = {100476//Wellcome Trust/United Kingdom ; 204672//Wellcome Trust/United Kingdom ; 203134//Wellcome Trust/United Kingdom ; 105021//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Coinfection ; Drug Discovery/*trends ; Humans ; Infection/*drug therapy/microbiology/parasitology/virology ; *Tropical Climate ; Tropical Medicine/*trends ; }, abstract = {Infectious tropical diseases have a huge effect in terms of mortality and morbidity, and impose a heavy economic burden on affected countries. These diseases predominantly affect the world's poorest people. Currently available drugs are inadequate for the majority of these diseases, and there is an urgent need for new treatments. This Review discusses some of the challenges involved in developing new drugs to treat these diseases and highlights recent progress. While there have been notable successes, there is still a long way to go.}, } @article {pmid30046072, year = {2018}, author = {Butler, KT and Davies, DW and Cartwright, H and Isayev, O and Walsh, A}, title = {Machine learning for molecular and materials science.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {547-555}, doi = {10.1038/s41586-018-0337-2}, pmid = {30046072}, issn = {1476-4687}, abstract = {Here we summarize recent progress in machine learning for the chemical sciences. We outline machine-learning techniques that are suitable for addressing research questions in this domain, as well as future directions for the field. We envisage a future in which the design, synthesis, characterization and application of molecules and materials is accelerated by artificial intelligence.}, } @article {pmid30046071, year = {2018}, author = {Ferguson, NM}, title = {Challenges and opportunities in controlling mosquito-borne infections.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {490-497}, doi = {10.1038/s41586-018-0318-5}, pmid = {30046071}, issn = {1476-4687}, mesh = {Animals ; Dengue/mortality/*prevention & control/transmission ; Gene Drive Technology ; Goals ; Humans ; Incidence ; Malaria/mortality/*prevention & control/transmission ; Mosquito Control/*methods ; Mosquito Vectors/genetics/microbiology ; Pest Control, Biological/methods ; Vaccines ; Wolbachia/pathogenicity ; }, abstract = {Mosquito-borne diseases remain a major cause of morbidity and mortality across the tropical regions. Despite much progress in the control of malaria, malaria-associated morbidity remains high, whereas arboviruses-most notably dengue-are responsible for a rising burden of disease, even in middle-income countries that have almost completely eliminated malaria. Here I discuss how new interventions offer the promise of considerable future reductions in disease burden. However, I emphasize that intervention programmes need to be underpinned by rigorous trials and quantitative epidemiological analyses. Such analyses suggest that the long-term goal of elimination is more feasible for dengue than for malaria, even if malaria elimination would offer greater overall health benefit to the public.}, } @article {pmid30046070, year = {2018}, author = {Timmermann, A and An, SI and Kug, JS and Jin, FF and Cai, W and Capotondi, A and Cobb, K and Lengaigne, M and McPhaden, MJ and Stuecker, MF and Stein, K and Wittenberg, AT and Yun, KS and Bayr, T and Chen, HC and Chikamoto, Y and Dewitte, B and Dommenget, D and Grothe, P and Guilyardi, E and Ham, YG and Hayashi, M and Ineson, S and Kang, D and Kim, S and Kim, W and Lee, JY and Li, T and Luo, JJ and McGregor, S and Planton, Y and Power, S and Rashid, H and Ren, HL and Santoso, A and Takahashi, K and Todd, A and Wang, G and Wang, G and Xie, R and Yang, WH and Yeh, SW and Yoon, J and Zeller, E and Zhang, X}, title = {El Niño-Southern Oscillation complexity.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {535-545}, doi = {10.1038/s41586-018-0252-6}, pmid = {30046070}, issn = {1476-4687}, mesh = {Climate Change ; *El Nino-Southern Oscillation ; Tropical Climate ; Water Movements ; }, abstract = {El Niño events are characterized by surface warming of the tropical Pacific Ocean and weakening of equatorial trade winds that occur every few years. Such conditions are accompanied by changes in atmospheric and oceanic circulation, affecting global climate, marine and terrestrial ecosystems, fisheries and human activities. The alternation of warm El Niño and cold La Niña conditions, referred to as the El Niño-Southern Oscillation (ENSO), represents the strongest year-to-year fluctuation of the global climate system. Here we provide a synopsis of our current understanding of the spatio-temporal complexity of this important climate mode and its influence on the Earth system.}, } @article {pmid30046069, year = {2018}, author = {Noguchi, M}, title = {The formation of solar-neighbourhood stars in two generations separated by 5 billion years.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {585-588}, doi = {10.1038/s41586-018-0329-2}, pmid = {30046069}, issn = {1476-4687}, abstract = {The chemical compositions of stars encode those of the gas from which they formed, providing important clues regarding the formation histories of galaxies. A powerful diagnostic is the abundance of α elements (O, Mg, Si, S, Ca and Ti) relative to iron, [α/Fe]. The α elements are synthesized and injected into the interstellar medium by type II supernovae, which occur about ten million years after their originating stars form; by contrast, iron is returned to the interstellar medium by type Ia supernovae, which occur after a much longer timescale of roughly one billion years1. Periods of rapid star formation therefore tend to produce high-[α/Fe] stellar populations (because only type II supernovae have time to contribute to interstellar-medium enrichment as the stellar population forms), whereas low-[α/Fe] stars require periods of star formation that last more than a few billion years (over which timescales type Ia supernovae begin to affect the elemental composition of the interstellar medium more strongly than type II supernovae). The existence of two distinct groups of stars in the solar neighbourhood2-7, one with high [α/Fe] and the other with low [α/Fe], therefore suggests two different origins, but the mechanism by which this bimodal distribution arose remains unknown. Here we use a model of disk-galaxy evolution to show that the two episodes of star formation8 predicted by the 'cold flow' theory of galactic gas accretion9,10 also explain the observed chemical bimodality. In this scenario, the high-[α/Fe] stars form early, during an initial phase of accretion that involves infalling streams of cold primordial gas. There is then a hiatus of around two billion years until the shock-heated gas in the galactic dark-matter halo has cooled as a result of radiation and can itself commence accretion. The low-[α/Fe] stars form during this second phase. The peaks in these two star-formation episodes are separated by around five billion years. In addition, the large-scale variation in the abundance patterns of these two stellar populations that has been observed for the Milky Way5,7 is partially explained by the spatial variation in this gas-accretion history.}, } @article {pmid30046068, year = {2018}, author = {Ezzati, M and Pearson-Stuttard, J and Bennett, JE and Mathers, CD}, title = {Acting on non-communicable diseases in low- and middle-income tropical countries.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {507-516}, doi = {10.1038/s41586-018-0306-9}, pmid = {30046068}, issn = {1476-4687}, mesh = {Animals ; Cardiovascular Diseases/etiology/genetics/mortality/therapy ; Developing Countries/economics/*statistics & numerical data ; Humans ; Infection/complications/epidemiology ; Neoplasms/etiology/genetics/mortality/therapy ; Noncommunicable Diseases/economics/mortality/*prevention & control/therapy ; Nutritional Status ; Poverty/statistics & numerical data ; *Tropical Climate ; }, abstract = {The classical portrayal of poor health in tropical countries is one of infections and parasites, contrasting with wealthy Western countries, where unhealthy diet and behaviours cause non-communicable diseases (NCDs) such as heart disease and cancer. Using international mortality data, we show that most NCDs cause more deaths at every age in low- and middle-income tropical countries than in high-income Western countries. Causes of NCDs in low- and middle-income countries include poor nutrition and living environment, infections, insufficient taxation and regulation of tobacco and alcohol, and under-resourced and inaccessible healthcare. We identify a comprehensive set of actions across health, social, economic and environmental sectors that could confront NCDs in low- and middle-income tropical countries and reduce global health inequalities.}, } @article {pmid30046067, year = {2018}, author = {Mitchard, ETA}, title = {The tropical forest carbon cycle and climate change.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {527-534}, doi = {10.1038/s41586-018-0300-2}, pmid = {30046067}, issn = {1476-4687}, mesh = {Animals ; *Carbon Cycle ; Carbon Sequestration ; Environmental Policy ; *Forests ; *Global Warming/prevention & control ; Sustainable Development ; Trees/*metabolism ; *Tropical Climate ; }, abstract = {Tropical forests make an approximately neutral contribution to the global carbon cycle, with intact and recovering forests taking in as much carbon as is released through deforestation and degradation. In the near future, tropical forests are likely to become a carbon source, owing to continued forest loss and the effect of climate change on the ability of the remaining forests to capture excess atmospheric carbon dioxide. This will make it harder to limit global warming to below 2 °C. Encouragingly, recent international agreements commit to halting deforestation and degradation, but a lack of fundamental data for use in monitoring and model design makes policy action difficult.}, } @article {pmid30045882, year = {2018}, author = {Diez, A}, title = {Liquid water on Mars.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {448-449}, doi = {10.1126/science.aau1829}, pmid = {30045882}, issn = {1095-9203}, mesh = {Exobiology ; Extraterrestrial Environment ; *Mars ; *Water ; }, } @article {pmid30045881, year = {2018}, author = {Orosei, R and Lauro, SE and Pettinelli, E and Cicchetti, A and Coradini, M and Cosciotti, B and Di Paolo, F and Flamini, E and Mattei, E and Pajola, M and Soldovieri, F and Cartacci, M and Cassenti, F and Frigeri, A and Giuppi, S and Martufi, R and Masdea, A and Mitri, G and Nenna, C and Noschese, R and Restano, M and Seu, R}, title = {Radar evidence of subglacial liquid water on Mars.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {490-493}, doi = {10.1126/science.aar7268}, pmid = {30045881}, issn = {1095-9203}, abstract = {The presence of liquid water at the base of the martian polar caps has long been suspected but not observed. We surveyed the Planum Australe region using the MARSIS (Mars Advanced Radar for Subsurface and Ionosphere Sounding) instrument, a low-frequency radar on the Mars Express spacecraft. Radar profiles collected between May 2012 and December 2015 contain evidence of liquid water trapped below the ice of the South Polar Layered Deposits. Anomalously bright subsurface reflections are evident within a well-defined, 20-kilometer-wide zone centered at 193°E, 81°S, which is surrounded by much less reflective areas. Quantitative analysis of the radar signals shows that this bright feature has high relative dielectric permittivity (>15), matching that of water-bearing materials. We interpret this feature as a stable body of liquid water on Mars.}, } @article {pmid30045862, year = {2018}, author = {Xing, Z and Caciagli, A and Cao, T and Stoev, I and Zupkauskas, M and O'Neill, T and Wenzel, T and Lamboll, R and Liu, D and Eiser, E}, title = {Microrheology of DNA hydrogels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8137-8142}, pmid = {30045862}, issn = {1091-6490}, mesh = {Biophysical Phenomena ; Biophysics ; DNA/*chemistry/radiation effects ; Diffusion ; Elasticity ; Hydrogels/*chemistry/radiation effects ; Lasers, Semiconductor ; Nanotechnology ; Polymers/chemistry ; *Rheology ; Spectrum Analysis ; Temperature ; Transition Temperature ; Viscosity ; }, abstract = {A key objective in DNA-based material science is understanding and precisely controlling the mechanical properties of DNA hydrogels. We perform microrheology measurements using diffusing wave spectroscopy (DWS) to investigate the viscoelastic behavior of a hydrogel made of Y-shaped DNA (Y-DNA) nanostars over a wide range of frequencies and temperatures. We observe a clear liquid-to-gel transition across the melting temperature region for which the Y-DNA bind to each other. Our measurements reveal a cross-over between the elastic [Formula: see text] and loss modulus [Formula: see text] around the melting temperature [Formula: see text] of the DNA building blocks, which coincides with the systems percolation transition. This transition can be easily shifted in temperature by changing the DNA bond length between the Y shapes. Using bulk rheology as well, we further show that, by reducing the flexibility between the Y-DNA bonds, we can go from a semiflexible transient network to a more energy-driven hydrogel with higher elasticity while keeping the microstructure the same. This level of control in mechanical properties will facilitate the design of more sensitive molecular sensing tools and controlled release systems.}, } @article {pmid30045768, year = {2018}, author = {Khadka, P and Basnet, RB and Rijal, BP and Sherchand, JB}, title = {Correction to: Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {505}, pmid = {30045768}, issn = {1756-0500}, abstract = {Following publication of the original article [1], a typesetting mistake is reported. The captions of Figure 2 and Figure 3 were interchanged. The incorrect and correct combination of the figures and captions are given in this Correction and the original article has been updated.}, } @article {pmid30045760, year = {2018}, author = {Hu, J and Koh, H and He, L and Liu, M and Blaser, MJ and Li, H}, title = {A two-stage microbial association mapping framework with advanced FDR control.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {131}, pmid = {30045760}, issn = {2049-2618}, support = {R01 DK090989/DK/NIDDK NIH HHS/United States ; R01 DK110014/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*classification ; Computational Biology/*methods ; Humans ; Microbiota ; Phylogeny ; }, abstract = {BACKGROUND: In microbiome studies, it is important to detect taxa which are associated with pathological outcomes at the lowest definable taxonomic rank, such as genus or species. Traditionally, taxa at the target rank are tested for individual association, followed by the Benjamini-Hochberg (BH) procedure to control for false discovery rate (FDR). However, this approach neglects the dependence structure among taxa and may lead to conservative results. The taxonomic tree of microbiome data represents alignment from phylum to species rank and characterizes evolutionary relationships across microbial taxa. Taxa that are closer on the tree usually have similar responses to the exposure (environment). The statistical power in microbial association tests can be enhanced by efficiently employing the prior evolutionary information via the taxonomic tree.

METHODS: We propose a two-stage microbial association mapping framework (massMap) which uses grouping information from the taxonomic tree to strengthen statistical power in association tests at the target rank. massMap first screens the association of taxonomic groups at a pre-selected higher taxonomic rank using a powerful microbial group test OMiAT. The method then proceeds to test the association for each candidate taxon at the target rank within the significant taxonomic groups identified in the first stage. Hierarchical BH (HBH) and selected subset testing (SST) procedures are evaluated to control the FDR for the two-stage structured tests.

RESULTS: Our simulations show that massMap incorporating OMiAT and the advanced FDR controlling methodologies largely alleviates the multiplicity issue. It is statistically more powerful than the traditional association mapping directly at the target rank while controlling the FDR at desired levels under most scenarios. In our real data analyses, massMap detects more or the same amount of associated species with smaller adjusted p values compared to the traditional method, which further illustrates the efficiency of the proposed framework. The R package of massMap is publicly available at https://sites.google.com/site/huilinli09/software and https://github.com/JiyuanHu/ .

CONCLUSIONS: massMap is a novel microbial association mapping framework and achieves additional efficiency by utilizing the intrinsic taxonomic structure of microbiome data.}, } @article {pmid30045727, year = {2018}, author = {Anand, R and Sarmah, DT and Chatterjee, S}, title = {Extracting proteins involved in disease progression using temporally connected networks.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {78}, pmid = {30045727}, issn = {1752-0509}, support = {25 (0258)/16/EMR-II.//Council of Scientific and Industrial Research/ ; }, abstract = {BACKGROUND: Metabolic disorders such as obesity and diabetes are diseases which develop gradually over time in an individual and through the perturbations of genes. Systematic experiments tracking disease progression at gene level are usually conducted giving a temporal microarray data. There is a need for developing methods to analyze such complex data and extract important proteins which could be involved in temporal progression of the data and hence progression of the disease.

RESULTS: In the present study, we have considered a temporal microarray data from an experiment conducted to study development of obesity and diabetes in mice. We have used this data along with an available Protein-Protein Interaction network to find a network of interactions between proteins which reproduces the next time point data from previous time point data. We show that the resulting network can be mined to identify critical nodes involved in the temporal progression of perturbations. We further show that published algorithms can be applied on such connected network to mine important proteins and show an overlap between outputs from published and our algorithms. The importance of set of proteins identified was supported by literature as well as was further validated by comparing them with the positive genes dataset from OMIM database which shows significant overlap.

CONCLUSIONS: The critical proteins identified from algorithms can be hypothesized to play important role in temporal progression of the data.}, } @article {pmid30045713, year = {2018}, author = {Shank, SD and Weaver, S and Kosakovsky Pond, SL}, title = {phylotree.js - a JavaScript library for application development and interactive data visualization in phylogenetics.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {276}, pmid = {30045713}, issn = {1471-2105}, support = {GM093939//National Institute of General Medical Sciences/ ; R01 AI134384/AI/NIAID NIH HHS/United States ; GM110749//National Institute of General Medical Sciences/ ; AI134384//National Institute of Allergy and Infectious Diseases/ ; R01 GM093939/GM/NIGMS NIH HHS/United States ; U01 GM110749/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: While several JavaScript packages for visualizing phylogenetic trees exist, most are best characterized as frameworks that are designed with a specific set of tasks in mind. Extending such packages to use cases that are not available as features often ends up being difficult. Moreover, existing packages tend to produce standalone widgets that are not designed to serve as middleware, as opposed to flexible tools that can integrate with other components of an application.

RESULTS: phylotree.js is a library that extends the popular data visualization framework d3.js, and is suitable for building JavaScript applications where users can view and interact with phylogenetic trees. The effects of such interactions can be captured and communicated to other package components, making it possible to engineer complex and responsive applications that include phylogenetic trees. phylotree.js implements several abstractions in addition to features, and comes with a documented application programming interface, thus promoting interoperability and extensibility. Example applications include a tool to visualize and annotate phylogenetic trees, a web application for comparative sequence analysis, a structural viewer that interacts with a large phylogenetic tree, and an interactive tanglegram.

CONCLUSIONS: phylotree.js is a useful tool and application module for a variety of computational biology software applications. The code is available on Github and is released under the MIT license.}, } @article {pmid30045694, year = {2018}, author = {Faria, MMP and Winston, BW and Surette, MG and Conly, JM}, title = {Bacterial DNA patterns identified using paired-end Illumina sequencing of 16S rRNA genes from whole blood samples of septic patients in the emergency room and intensive care unit.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {79}, pmid = {30045694}, issn = {1471-2180}, abstract = {BACKGROUND: Sepsis refers to clinical presentations ranging from mild body dysfunction to multiple organ failure. These clinical symptoms result from a systemic inflammatory response to pathogenic or potentially pathogenic microorganisms present systemically in the bloodstream. Current clinical diagnostics rely on culture enrichment techniques to identify bloodstream infections. However, a positive result is obtained in a minority of cases thereby limiting our knowledge of sepsis microbiology. Previously, a method of saponin treatment of human whole blood combined with a comprehensive bacterial DNA extraction protocol was developed. The results indicated that viable bacteria could be recovered down to 10 CFU/ml using this method. Paired-end Illumina sequencing of the 16S rRNA gene also indicated that the bacterial DNA extraction method enabled recovery of bacterial DNA from spiked blood. This manuscript outlines the application of this method to whole blood samples collected from patients with the clinical presentation of sepsis.

RESULTS: Blood samples from clinically septic patients were obtained with informed consent. Application of the paired-end Illumina 16S rRNA sequencing to saponin treated blood from intensive care unit (ICU) and emergency department (ED) patients indicated that bacterial DNA was present in whole blood. There were three clusters of bacterial DNA profiles which were distinguished based on the distribution of Streptococcus, Staphylococcus, and Gram-negative DNA. The profiles were examined alongside the patient's clinical data and indicated molecular profiling patterns from blood samples had good concordance with the primary source of infection.

CONCLUSIONS: Overall this study identified common bacterial DNA profiles in the blood of septic patients which were often associated with the patients' primary source of infection. These results indicated molecular bacterial DNA profiling could be further developed as a tool for clinical diagnostics for bloodstream infections.}, } @article {pmid30045693, year = {2018}, author = {Mura-Jornet, I and Pimentel, C and Dantas, GPM and Petry, MV and González-Acuña, D and Barbosa, A and Lowther, AD and Kovacs, KM and Poulin, E and Vianna, JA}, title = {Correction to: Chinstrap penguin population genetic structure: one or more populations along the Southern Ocean?.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {117}, pmid = {30045693}, issn = {1471-2148}, abstract = {Correction to: BMC Evolutionary Biology (2018) 18:90 https://doi.org/10.1186/s12862-018-1207-0 .}, } @article {pmid30045691, year = {2018}, author = {Liu, Y and Luo, M and Li, Q and Lu, J and Zhao, M and Qu, H}, title = {CIGene: a literature-based online resource for cancer initiation genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {552}, pmid = {30045691}, issn = {1471-2164}, support = {31671375//National Natural Science Foundation of China/ ; 81273149, 81473040, 81673267//National Natural Science Foundation of China/ ; No. 2017YFC1201200//the National Key Research and Development Program of China/ ; }, mesh = {Breast Neoplasms/genetics/mortality ; *Databases, Genetic ; Female ; *Genes, Neoplasm ; Genes, Tumor Suppressor ; Humans ; Internet ; Mutation ; Neoplasms/genetics/metabolism ; Oncogenes ; Periodicals as Topic ; }, abstract = {BACKGROUND: Cancer initiation genes (CIGs) are genes that can directly promote cell proliferation or induce cancer. There are thousands of published studies identifying various CIGs; however, no systematic collection or description is available.

RESULTS: To construct a CIG reference for genetic screening, we have collected 177 human genes curated from 1507 PubMed abstracts. To facilitate data queries and browsing, the identified CIGs along with extensive bioinformatic annotations were stored in an online database called CIGene. Initial functional analysis revealed an overlooked role for cell motility in cancer initiation. Subsequent cross-referencing of known tumor suppressor genes and oncogenes against the 177 CIGs identified 96 and 81 CIGs with and without known oncogenic roles, respectively. Successive network analyses of all 177 CIGs determined that the two groups of genes were more likely to link within their group. The distinct molecular functions for these groups were also confirmed with functional studies. While the 96 known oncogenic genes had fundamental roles in gene regulation and signaling, the remaining 81 genes possessed more ancillary functions, such enhancer binding. Further network and mutational analysis of the 96 known oncogenic genes revealed that mutations in these genes were highly prevalent in multiple cancers. By focusing on breast cancer, we found that 32 of the 96 genes with mutations in breast cancers were significantly associated with patient survival.

CONCLUSIONS: As the first literature-based online resource for CIGs, CIGene will serve as a useful gateway for the systematic analysis of cancer initiation. CIGene is freely available to all academic users at http://soft.bioinfo-minzhao.org/cigene/ .}, } @article {pmid30045017, year = {2018}, author = {Neeley, B and Overholt, T and Artz, E and Kinsey, SG and Marsat, G}, title = {Selective and Context-Dependent Social and Behavioral Effects of Δ9-Tetrahydrocannabinol in Weakly Electric Fish.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {4}, pages = {214-227}, doi = {10.1159/000490171}, pmid = {30045017}, issn = {1421-9743}, support = {R03 DA039335/DA/NIDA NIH HHS/United States ; R15 AR066806/AR/NIAMS NIH HHS/United States ; }, abstract = {Cannabinoid (CB) receptors are widespread in the nervous system and influence a variety of behaviors. Weakly electric fish have been a useful model system in the study of the neural basis of behavior, but we know nothing of the role played by the CB system. Here, we determine the overall behavioral effect of a nonselective CB receptor agonist, namely Δ9-tetrahydrocannabinol (THC), in the weakly electric fish Apte-ronotus leptorhynchus. Using various behavioral paradigms involving social stimuli, we show that THC decreases locomotor behavior, as in many species, and influences communication and social behavior. Across the different experiments, we found that the propensity to emit communication signals (chirps) and seek social interactions was affected in a context-dependent manner. We explicitly tested this hypothesis by comparing the behavioral effects of THC injection in fish placed in a novel versus a familiar social and physical environment. THC-injected fish were less likely to chirp than control fish in familiar situations but not in novel ones. The tendency to be in close proximity to other fish was affected only in novel environments, with control fish clustering more than THC-injected ones. By identifying behaviors affected by CB agonists, our study can guide further comparative and neurophysiological studies of the role of the CB system using a weakly electric fish as a model.}, } @article {pmid30044889, year = {2018}, author = {Brown, LL and Cohen, B and Tabor, D and Zappalà, G and Maruvada, P and Coates, PM}, title = {The vitamin D paradox in Black Americans: a systems-based approach to investigating clinical practice, research, and public health - expert panel meeting report.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 6}, pages = {6}, pmid = {30044889}, issn = {1753-6561}, abstract = {The Office of Dietary Supplements, the National Institute on Minority Health and Health Disparities, the National Institute on Aging, and the National Institute of Diabetes and Digestive and Kidney Diseases, all components of the U.S. National Institutes of Health, co-sponsored an expert panel meeting to discuss the vitamin D paradox in Black Americans. The paradox is that despite markedly low (or "deficient") measures of vitamin D status in Black Americans, the incidence of falls, fractures, or osteopenia are significantly lower compared to White American counterparts with similar vitamin D status. Six panelists were invited to engage in guided discussions on the state of the science with respect to key knowledge gaps impacting vitamin D status and bone health. They were also asked to reflect on best approaches for advancing the science. A central theme throughout the discussions was that there may be many factors that impact Vitamin D levels in Black Americans and understanding these factors may be key to understanding mechanisms for improving bone health in all populations. Data presented showed that although adiposity, skin pigmentation, vitamin D binding protein polymorphisms, and genetics all contributed to differences in 25(OH)D levels in Black vs. White Americans, no one factor alone could fully explain the vitamin D paradox in Black Americans. However, the panelists did agree that the paradox is significant and warrants further investigation. There was consensus that Black Americans gained no skeletal benefits from high doses of vitamin D supplementation, and that high levels of the biomarker of vitamin D status, serum 25-hydroxyvitamin D or 25(OH)D, in this population are almost certain to result in adverse effects. Some panelists proposed that additional studies are needed so that the Institute of Medicine (IOM) can better define the safe upper limits of vitamin D intake in this and other subpopulations. Others suggested a need for better, more generalizable biomarkers of bone health to advance the science.}, } @article {pmid30044888, year = {2018}, author = {Thompson, J and Undie, CC and Amin, A and Johnson, BR and Khosla, R and Ouedraogo, L and Nkurunziza, T and Rich, S and Westley, E and Garcia, M and Birungi, H and Askew, I}, title = {Harmonizing national abortion and pregnancy prevention laws and policies for sexual violence survivors with the Maputo Protocol: proceedings of a 2016 regional technical meeting in sub-Saharan Africa.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 5}, pages = {5}, doi = {10.1186/s12919-018-0101-5}, pmid = {30044888}, issn = {1753-6561}, abstract = {In April 2016, the Population Council, in partnership with the World Health Organization (WHO) and the International Consortium for Emergency Contraception, convened a regional meeting in Lusaka, Zambia, geared toward supporting countries in East and Southern Africa in meeting their obligations under the Maputo Protocol. These obligations include expanding access to women's reproductive health services - especially women survivors of sexual violence. Government and civil society representatives from six countries participated: Botswana, Ethiopia, Kenya, Malawi, Rwanda, and Zambia. Countries were selected based on to their being priority settings for the projects that sponsored the meeting, coupled with the fact that they were each far enough along in addressing post-rape care to be able to develop concrete policy, programming, and/or legal action plans by the end of the meeting. The meeting was the first activity in a joint project of technical assistance by the conveners, aimed at strengthening access to comprehensive post-rape care for survivors of sexual violence. It aimed to sensitize Member States to their obligations under the Maputo Protocol to expand women's access to emergency contraception (EC) and safe abortion services, and to inspire them to do so by providing information, research evidence, and a platform for discussion. The meeting deliberations fostered a better understanding of opportunities to broaden access to EC and safe abortion for survivors in the region. Discussions on EC in this regard centered on strengthening EC delivery in the clinical context, decentralizing EC services, increasing community awareness, and overcoming policy barriers. Safe abortion discussions focused primarily on legislation, policy, and integrating these services into existing services for sexual violence survivors. Country-specific action plans were developed to address gaps and weaknesses. The regional technical meeting concluded with a discussion of practical steps that participants could take to facilitate legal, policy, and program reform with respect to pregnancy prevention and safe abortion in their respective countries. The steps revolved around three mainly areas, namely: establishing an evidence base to inform action; creating forums for discussing the issues; and drafting action points to carry the momentum from the meeting forward. This paper details the proceedings from this regional technical meeting - proceedings that are of interest to the field of sexual and gender-based violence (and reproductive health, more broadly) as challenges faced by countries in implementing the Maputo Protocol are outlined, and evidence-informed and practice-based strategies for addressing these challenges are provided.}, } @article {pmid30044886, year = {2018}, author = {Pocock, NS and Suphanchaimat, R and Chan, CK and Faller, EM and Harrigan, N and Pillai, V and Wickramage, K}, title = {Reflections on migrant and refugee health in Malaysia and the ASEAN region.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 4}, pages = {4}, pmid = {30044886}, issn = {1753-6561}, abstract = {Migrants and refugees face challenges accessing both healthcare and good social determinants of health in Malaysia. Participants at the "Migrant and Refugee Health in Malaysia workshop, Kuala Lumpur, 9-10 November 2017" scoped these challenges within the regional ASEAN context, identifying gaps in knowledge and practical steps forward to improve the evidence base in the Malaysia.}, } @article {pmid30044688, year = {2019}, author = {Close, HG}, title = {Compound-Specific Isotope Geochemistry in the Ocean.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {27-56}, doi = {10.1146/annurev-marine-121916-063634}, pmid = {30044688}, issn = {1941-0611}, abstract = {Compound-specific isotope analysis encompasses a variety of methods for examining the naturally occurring isotope ratios of individual organic molecules. In marine environments, these methods have revealed heterogeneous sources and alteration processes that underlie the more commonly measured isotope ratios of bulk materials, as well as revealing signatures of marine metabolisms that may otherwise be impossible to isolate. Recently, compound-specific isotopic techniques have improved the reconstruction of metazoan diets and revealed a new potential of metazoan biomass as an archive of paleoecological information. Despite six decades of practice and a diversity of applications, the use of compound-specific isotopic techniques remains uncommon in marine studies. This review examines broad theoretical motivations behind compound-specific isotopic approaches, some applications to studies of marine carbon cycling and trophic relationships, and methodological limitations. In coming years, improvements in analytical efficiency and molecular or intramolecular specificity may transform compound-specific isotope analysis into a tool that can be applied more broadly and help to build global oceanographic data sets.}, } @article {pmid30044650, year = {2018}, author = {Janssen, A and Colmenares, SU and Karpen, GH}, title = {Heterochromatin: Guardian of the Genome.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {265-288}, doi = {10.1146/annurev-cellbio-100617-062653}, pmid = {30044650}, issn = {1530-8995}, abstract = {Constitutive heterochromatin is a major component of the eukaryotic nucleus and is essential for the maintenance of genome stability. Highly concentrated at pericentromeric and telomeric domains, heterochromatin is riddled with repetitive sequences and has evolved specific ways to compartmentalize, silence, and repair repeats. The delicate balance between heterochromatin epigenetic maintenance and cellular processes such as mitosis and DNA repair and replication reveals a highly dynamic and plastic chromatin domain that can be perturbed by multiple mechanisms, with far-reaching consequences for genome integrity. Indeed, heterochromatin dysfunction provokes genetic turmoil by inducing aberrant repeat repair, chromosome segregation errors, transposon activation, and replication stress and is strongly implicated in aging and tumorigenesis. Here, we summarize the general principles of heterochromatin structure and function, discuss the importance of its maintenance for genome integrity, and propose that more comprehensive analyses of heterochromatin roles in tumorigenesis will be integral to future innovations in cancer treatment.}, } @article {pmid30044649, year = {2018}, author = {Curcio, M and Bradke, F}, title = {Axon Regeneration in the Central Nervous System: Facing the Challenges from the Inside.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {495-521}, doi = {10.1146/annurev-cellbio-100617-062508}, pmid = {30044649}, issn = {1530-8995}, abstract = {After an injury in the adult mammalian central nervous system (CNS), lesioned axons fail to regenerate. This failure to regenerate contrasts with axons' remarkable potential to grow during embryonic development and after an injury in the peripheral nervous system (PNS). Several intracellular mechanisms-including cytoskeletal dynamics, axonal transport and trafficking, signaling and transcription of regenerative programs, and epigenetic modifications-control axon regeneration. In this review, we describe how manipulation of intrinsic mechanisms elicits a regenerative response in different organisms and how strategies are implemented to form the basis of a future regenerative treatment after CNS injury.}, } @article {pmid30044648, year = {2018}, author = {Davis, AA and Leyns, CEG and Holtzman, DM}, title = {Intercellular Spread of Protein Aggregates in Neurodegenerative Disease.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {545-568}, doi = {10.1146/annurev-cellbio-100617-062636}, pmid = {30044648}, issn = {1530-8995}, support = {K08 NS101118/NS/NINDS NIH HHS/United States ; }, abstract = {Most neurodegenerative diseases are characterized by the accumulation of protein aggregates, some of which are toxic to cells. Mounting evidence demonstrates that in several diseases, protein aggregates can pass from neuron to neuron along connected networks, although the role of this spreading phenomenon in disease pathogenesis is not completely understood. Here we briefly review the molecular and histopathological features of protein aggregation in neurodegenerative disease, we summarize the evidence for release of proteins from donor cells into the extracellular space, and we highlight some other mechanisms by which protein aggregates might be transmitted to recipient cells. We also discuss the evidence that supports a role for spreading of protein aggregates in neurodegenerative disease pathogenesis and some limitations of this model. Finally, we consider potential therapeutic strategies to target spreading of protein aggregates in the treatment of neurodegenerative diseases.}, } @article {pmid30043554, year = {2018}, author = {Takamatsu, D and Yoshida, E and Watando, E and Ueno, Y and Kusumoto, M and Okura, M and Osaki, M and Katsuda, K}, title = {A frameshift mutation in the rRNA large subunit methyltransferase gene rlmA II determines the susceptibility of a honey bee pathogen Melissococcus plutonius to mirosamicin.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4431-4443}, doi = {10.1111/1462-2920.14365}, pmid = {30043554}, issn = {1462-2920}, support = {//Ministry of Agriculture, Forestry and Fisheries of Japan/ ; }, abstract = {American foulbrood (AFB) and European foulbrood (EFB) caused by Paenibacillus larvae and Melissococcus plutonius, respectively, are major bacterial infections of honey bees. Although macrolides (mirosamicin [MRM] and tylosin) have been used to prevent AFB in Japan, macrolide-resistant P. larvae have yet to be found. In this study, we revealed that both MRM-resistant and -susceptible strains exist in Japanese M. plutonius and that a methyltransferase gene (rlmA II) was disrupted exclusively in MRM-susceptible strains due to a single-nucleotide insertion. The M. plutonius RlmAII modified G748 of 23S rRNA, and the deletion of rlmA II resulted in increased susceptibility to MRM and the loss of modification at G748, suggesting that methylation at G748 by RlmAII confers MRM resistance in M. plutonius. The single-nucleotide mutation in MRM-susceptible strains was easily repaired by spontaneous deletion of the inserted nucleotide; however, intact rlmA II was only found in Japanese M. plutonius and not in a Paraguayan strain tested or any of the whole-genome-sequenced European strains. MRM has been used in apiculture only in Japan. Although M. plutonius is not the target of this drug, the use of MRM as a prophylactic drug for AFB may have influenced the antibiotic susceptibility of the causative agent of EFB.}, } @article {pmid30043533, year = {2018}, author = {Monteil, CL and Perrière, G and Menguy, N and Ginet, N and Alonso, B and Waisbord, N and Cruveiller, S and Pignol, D and Lefèvre, CT}, title = {Genomic study of a novel magnetotactic Alphaproteobacteria uncovers the multiple ancestry of magnetotaxis.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4415-4430}, doi = {10.1111/1462-2920.14364}, pmid = {30043533}, issn = {1462-2920}, support = {//European Regional Development Fund/ ; ANR-14-CE35-0018//DFG-ANR project/ ; DJ/ST/IP/2013/D-112//Appel à Projets en Génomique Environnementale - CNRS/ ; ANR-16-TERC-0025-01//French National Research Agency/ ; }, abstract = {Ecological and evolutionary processes involved in magnetotactic bacteria (MTB) adaptation to their environment have been a matter of debate for many years. Ongoing efforts for their characterization are progressively contributing to understand these processes, including the genetic and molecular mechanisms responsible for biomineralization. Despite numerous culture-independent MTB characterizations, essentially within the Proteobacteria phylum, only few species have been isolated in culture because of their complex growth conditions. Here, we report a newly cultivated magnetotactic, microaerophilic and chemoorganoheterotrophic bacterium isolated from the Mediterranean Sea in Marseille, France: Candidatus Terasakiella magnetica strain PR-1 that belongs to an Alphaproteobacteria genus with no magnetotactic relative. By comparing the morphology and the whole genome shotgun sequence of this MTB with those of closer relatives, we brought further evidence that the apparent vertical ancestry of magnetosome genes suggested by previous studies within Alphaproteobacteria hides a more complex evolutionary history involving horizontal gene transfers and/or duplication events before and after the emergence of Magnetospirillum, Magnetovibrio and Magnetospira genera. A genome-scale comparative genomics analysis identified several additional candidate functions and genes that could be specifically associated to MTB lifestyle in this class of bacteria.}, } @article {pmid30043505, year = {2018}, author = {Cupit, C and Lomstein, BA and Kjeldsen, KU}, title = {Contrasting community composition of endospores and vegetative Firmicutes in a marine sediment suggests both endogenous and exogenous sources of endospore accumulation.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12679}, pmid = {30043505}, issn = {1758-2229}, support = {no DNRF104//Danmarks Grundforskningsfond/ ; no 294200//European Research Council (ERC) under the European Union's Seventh Framework Programme (FP7)/ ; FP7//Danish National Research Foundation/ ; DNRF104//Danish National Research Foundation/ ; }, abstract = {Bacterial endospores are highly abundant in marine sediments, but their taxonomic identity and ecology is largely unknown. We selectively extracted DNA from endospores and vegetative cells and sequenced 16S rRNA genes to characterize the composition of the endospore and vegetative Firmicutes communities in the sediment and water column of Aarhus Bay (Denmark). The endospore community in the sediment was dominated by the families Bacillaceae, Lachnospiraceae, Clostridiaceae and Ruminoccocaceae. These families were also represented in the vegetative community in the sediment and the endospore community in the water column. OTUs of high relative abundance in the endospore community were also represented in the vegetative Firmicutes community. Other OTUs were exclusively found in the endospore communities. This suggests that endospores accumulate in marine sediments due to passive deposition from the water column and sporulation of vegetative cells in the sediment. Some OTUs were detected in the endospore community of the water column and the vegetative community the sediment indicating that endospores deposited from the water column may germinate upon burial/deposition in the sediment. We provide novel insight into the composition of endospore communities in marine sediments and highlight their role in microbial dispersal and as a seed bank in subsurface sediments.}, } @article {pmid30043488, year = {2018}, author = {Sandegren, L and Stedt, J and Lustig, U and Bonnedahl, J and Andersson, DI and Järhult, JD}, title = {Long-term carriage and rapid transmission of extended spectrum beta-lactamase-producing E. coli within a flock of Mallards in the absence of antibiotic selection.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {576-582}, doi = {10.1111/1758-2229.12681}, pmid = {30043488}, issn = {1758-2229}, abstract = {Wild birds have been suggested as transmitters and reservoirs for antibiotic resistant bacteria. We performed an experimental study investigating carriage time and interindividual transmission of extended spectrum beta-lactamase- (ESBL-)producing Escherichia coli in Mallards (Anas platyrhynchos) to assess if the birds carry the bacteria long enough to transfer them geographically during migration. Mallards were inoculated intraoesophageally with four different strains of ESBL-producing E. coli and kept together in a flock. The ESBL-strains belonged to sequence types previously shown to spread between birds and humans. Culturing from faecal samples showed presence of ESBL-producing E. coli the entire 29 day experimental period. An extensive and rapid transmission of the different ESBL-strains between individuals (including non-inoculated controls) was observed. In necropsy samples, we detected ESBL-strains in the cecum even in faeces-negative birds, indicating that this part of the intestine could function as a reservoir of resistant bacteria. We demonstrate that birds can carry ESBL-producing E. coli for long enough times to travel far during migration and the extensive interindividual transmission suggests spread between individuals in a dense bird population as a mechanism that allow persistence of resistant bacteria.}, } @article {pmid30043484, year = {2018}, author = {Lampe, RH and Cohen, NR and Ellis, KA and Bruland, KW and Maldonado, MT and Peterson, TD and Till, CP and Brzezinski, MA and Bargu, S and Thamatrakoln, K and Kuzminov, FI and Twining, BS and Marchetti, A}, title = {Divergent gene expression among phytoplankton taxa in response to upwelling.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3069-3082}, doi = {10.1111/1462-2920.14361}, pmid = {30043484}, issn = {1462-2920}, support = {OCE-1341479//National Science Foundation/ ; OCE-1259776//National Science Foundation/ ; OCE-1334387//National Science Foundation/ ; OCE-1333929//National Science Foundation/ ; OCE-1334632//National Science Foundation/ ; OCE-1334935//National Science Foundation/ ; }, abstract = {Frequent blooms of phytoplankton occur in coastal upwelling zones creating hotspots of biological productivity in the ocean. As cold, nutrient-rich water is brought up to sunlit layers from depth, phytoplankton are also transported upwards to seed surface blooms that are often dominated by diatoms. The physiological response of phytoplankton to this process, commonly referred to as shift-up, is characterized by increases in nitrate assimilation and rapid growth rates. To examine the molecular underpinnings behind this phenomenon, metatranscriptomics was applied to a simulated upwelling experiment using natural phytoplankton communities from the California Upwelling Zone. An increase in diatom growth following 5 days of incubation was attributed to the genera Chaetoceros and Pseudo-nitzschia. Here, we show that certain bloom-forming diatoms exhibit a distinct transcriptional response that coordinates shift-up where diatoms exhibited the greatest transcriptional change following upwelling; however, comparison of co-expressed genes exposed overrepresentation of distinct sets within each of the dominant phytoplankton groups. The analysis revealed that diatoms frontload genes involved in nitrogen assimilation likely in order to outcompete other groups for available nitrogen during upwelling events. We speculate that the evolutionary success of diatoms may be due, in part, to this proactive response to frequently encountered changes in their environment.}, } @article {pmid30043404, year = {2018}, author = {Johns, CT and Grubb, AR and Nissimov, JI and Natale, F and Knapp, V and Mui, A and Fredricks, HF and Van Mooy, BAS and Bidle, KD}, title = {The mutual interplay between calcification and coccolithovirus infection.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14362}, pmid = {30043404}, issn = {1462-2920}, support = {GBMF3301 to BVM//Gordon and Betty Moore Foundation/ ; GBMF3789 to KDB//Gordon and Betty Moore Foundation/ ; OCE-1537951//National Science Foundation/ ; OCE-1559179 to KDB//National Science Foundation/ ; }, abstract = {Two prominent characteristics of marine coccolithophores are their secretion of coccoliths and their susceptibility to infection by coccolithoviruses (EhVs), both of which display variation among cells in culture and in natural populations. We examined the impact of calcification on infection by challenging a variety of Emiliania huxleyi strains at different calcification states with EhVs of different virulence. Reduced cellular calcification was associated with increased infection and EhV production, even though calcified cells and associated coccoliths had significantly higher adsorption coefficients than non-calcified (naked) cells. Sialic acid glycosphingolipids, molecules thought to mediate EhV infection, were generally more abundant in calcified cells and enriched in purified, sorted coccoliths, suggesting a biochemical link between calcification and adsorption rates. In turn, viable EhVs impacted cellular calcification absent of lysis by inducing dramatic shifts in optical side scatter signals and a massive release of detached coccoliths in a subpopulation of cells, which could be triggered by resuspension of healthy, calcified host cells in an EhV-free, 'induced media'. Our findings show that calcification is a key component of the E. huxleyi-EhV arms race and an aspect that is critical both to the modelling of these host-virus interactions in the ocean and interpreting their impact on the global carbon cycle.}, } @article {pmid30043120, year = {2018}, author = {Tak, HJ and Piao, Z and Kim, HJ and Lee, SH}, title = {Axin2 overexpression promotes the early epithelial disintegration and fusion of facial prominences during avian lip development.}, journal = {Development genes and evolution}, volume = {228}, number = {5}, pages = {197-211}, pmid = {30043120}, issn = {1432-041X}, support = {NRF-2017R1A2B4005319//National Research Foundation of Korea/International ; }, mesh = {Animals ; Avian Proteins/*genetics ; Axin Protein/*genetics ; Beak/*embryology/metabolism ; Cell Death ; Chick Embryo/cytology/metabolism ; Chickens/*genetics/*growth & development/metabolism ; *Gene Expression Regulation, Developmental ; *Morphogenesis ; }, abstract = {The epithelial disintegration and the mesenchymal bridging are critical steps in the fusion of facial prominences during the upper lip development. These processes of epithelial-mesenchymal transition and programmed cell death are mainly influenced by Wnt signals. Axis inhibition protein2 (Axin2), a major component of the Wnt pathway, has been reported to be involved in lip development and cleft pathogenesis. We wanted to study the involvement of Axin2 in the lip development, especially during the epithelial disintegration of facial prominences. Our results show that Axin2 was expressed mainly in the epithelium of facial prominences and decreased when the prominences were about to contact each other between Hamburger-Hamilton stages 27 and 28 of chicken embryos. The epithelial integrity was destructed or kept intact by the local gain or loss of Axin2 expression, resulting in morphological changes in the facial processes and their skeletal derivatives including the maxilla, nasal, premaxilla bone, and their junctions without cleft formation. These changes were related to expression changes in nuclear β-catenin, pGSK3β, Slug, Smad3, E-cadherin, and p63. All these data indicate that Axin2 participates in the regulation of epithelial integrity and fusion by promoting epithelial disassociation, basement membrane breakdown, and seam loss during the fusion of facial prominences in lip development.}, } @article {pmid30042547, year = {2018}, author = {Sheldon, T}, title = {Preprints could promote confusion and distortion.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {445}, doi = {10.1038/d41586-018-05789-4}, pmid = {30042547}, issn = {1476-4687}, mesh = {*Access to Information/legislation & jurisprudence ; *Guidelines as Topic ; Journalism/standards ; Mass Media/*standards ; Peer Review, Research ; Periodicals as Topic ; *Public Sector ; Publishing/*standards ; Research/*standards ; }, } @article {pmid30042546, year = {2018}, author = {}, title = {Recognition for inspirational women in science.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {443-444}, doi = {10.1038/d41586-018-05801-x}, pmid = {30042546}, issn = {1476-4687}, mesh = {Child ; Child Care/supply & distribution ; Female ; Humans ; Internationality ; Mentoring/standards ; Minority Groups/education/statistics & numerical data ; Research Personnel/education/*standards/supply & distribution ; *Reward ; *Science/education/standards/statistics & numerical data ; Women ; Women's Rights/*standards ; Young Adult ; }, } @article {pmid30042545, year = {2018}, author = {}, title = {Open data offer risks and rewards for conservation.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {444}, doi = {10.1038/d41586-018-05800-y}, pmid = {30042545}, issn = {1476-4687}, } @article {pmid30042544, year = {2018}, author = {Perkel, JM}, title = {The hackers teaching old DNA sequencers new tricks.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {643-645}, doi = {10.1038/d41586-018-05769-8}, pmid = {30042544}, issn = {1476-4687}, } @article {pmid30042543, year = {2018}, author = {Mbah, O and Nkangu, M and Rogoff, Z}, title = {Don't ignore health-care impacts of Internet shutdowns.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {477}, doi = {10.1038/d41586-018-05797-4}, pmid = {30042543}, issn = {1476-4687}, mesh = {Asia ; Cameroon ; Conflict (Psychology) ; Delivery of Health Care/*statistics & numerical data ; Health Care Surveys ; Humans ; Internet/*supply & distribution ; Middle East ; *Politics ; }, } @article {pmid30042542, year = {2018}, author = {Rivers, CM and Scarpino, SV}, title = {Modelling the trajectory of disease outbreaks works.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {477}, doi = {10.1038/d41586-018-05798-3}, pmid = {30042542}, issn = {1476-4687}, } @article {pmid30042541, year = {2018}, author = {Ryan, BJ}, title = {The United States will lose money if it charges for Earth observation data.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {477}, doi = {10.1038/d41586-018-05796-5}, pmid = {30042541}, issn = {1476-4687}, } @article {pmid30042540, year = {2018}, author = {Forough, R and Mian, M and Klobas, A and Talada, J}, title = {From literature search to vaccine candidate without a lab.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {477}, doi = {10.1038/d41586-018-05790-x}, pmid = {30042540}, issn = {1476-4687}, } @article {pmid30042538, year = {2018}, author = {Whitehouse, P}, title = {Ancient ice sheet had a growth spurt.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {487-488}, doi = {10.1038/d41586-018-05760-3}, pmid = {30042538}, issn = {1476-4687}, } @article {pmid30042537, year = {2018}, author = {González Tudela, A and Cirac, JI}, title = {Quantum optics without photons.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {481-482}, doi = {10.1038/d41586-018-05738-1}, pmid = {30042537}, issn = {1476-4687}, } @article {pmid30042535, year = {2018}, author = {Glausiusz, J}, title = {How to deliver sound science in resource-poor regions.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {647-649}, doi = {10.1038/d41586-018-05768-9}, pmid = {30042535}, issn = {1476-4687}, } @article {pmid30042534, year = {2018}, author = {Reese, A}, title = {Ecologists try to speed up evolution to save Australian marsupial from toxic toads.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {451-452}, doi = {10.1038/d41586-018-05757-y}, pmid = {30042534}, issn = {1476-4687}, mesh = {Animals ; Australia ; Bufonidae ; Ecology ; *Gene Flow ; *Marsupialia ; }, } @article {pmid30042533, year = {2018}, author = {Castelvecchi, D}, title = {Big Bang telescope finale marks end of an era in cosmology.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {455-456}, doi = {10.1038/d41586-018-05788-5}, pmid = {30042533}, issn = {1476-4687}, } @article {pmid30042530, year = {2018}, author = {Silver, A}, title = {Philippines sweetens deal for scientists who return home.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {453-454}, doi = {10.1038/d41586-018-05600-4}, pmid = {30042530}, issn = {1476-4687}, mesh = {Climate Change ; Emigration and Immigration/statistics & numerical data ; Humans ; Internationality ; Laboratories ; Motivation ; Personnel Selection/economics/*methods ; Philippines ; Research/economics/*statistics & numerical data ; Research Personnel/*economics/*supply & distribution ; Workforce/economics/*statistics & numerical data ; }, } @article {pmid30042528, year = {2018}, author = {Else, H}, title = {Dutch publishing giant cuts off researchers in Germany and Sweden.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {454-455}, doi = {10.1038/d41586-018-05754-1}, pmid = {30042528}, issn = {1476-4687}, mesh = {Contracts/*economics/*legislation & jurisprudence ; Germany ; Libraries ; Negotiating ; Netherlands ; Open Access Publishing/economics/legislation & jurisprudence ; Periodicals as Topic/*economics/*legislation & jurisprudence ; *Research/economics ; Sweden ; Universities ; }, } @article {pmid30042524, year = {2018}, author = {Witze, A}, title = {Death-defying NASA mission will make humanity's closest approach to the Sun.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {452-453}, doi = {10.1038/d41586-018-05741-6}, pmid = {30042524}, issn = {1476-4687}, } @article {pmid30042506, year = {2018}, author = {Granda, JM and Donina, L and Dragone, V and Long, DL and Cronin, L}, title = {Publisher Correction: Controlling an organic synthesis robot with machine learning to search for new reactivity.}, journal = {Nature}, volume = {562}, number = {7728}, pages = {E26}, doi = {10.1038/s41586-018-0412-8}, pmid = {30042506}, issn = {1476-4687}, abstract = {The chemical structure formatting in Fig. 5 has been corrected online.}, } @article {pmid30042505, year = {2018}, author = {Szabo, E and Rampalli, S and Risueño, RM and Schnerch, A and Mitchell, R and Fiebig-Comyn, A and Levadoux-Martin, M and Bhatia, M}, title = {Author Correction: Direct conversion of human fibroblasts to multilineage blood progenitors.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {E32}, doi = {10.1038/s41586-018-0402-x}, pmid = {30042505}, issn = {1476-4687}, abstract = {In this Article, there were duplicated empty lanes in Supplementary Figs. 2e and 3b. The corrected figures are presented in the Supplementary Information to the accompanying Amendment. The original Article has not been corrected.}, } @article {pmid30042480, year = {2018}, author = {Burgess, DJ}, title = {Koala genome insights.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {533}, doi = {10.1038/s41576-018-0039-5}, pmid = {30042480}, issn = {1471-0064}, } @article {pmid30042479, year = {2018}, author = {Du Toit, A}, title = {Permafrost thawing and carbon metabolism.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {519}, doi = {10.1038/s41579-018-0066-4}, pmid = {30042479}, issn = {1740-1534}, } @article {pmid30042441, year = {2018}, author = {Delmont, TO and Quince, C and Shaiber, A and Esen, ÖC and Lee, ST and Rappé, MS and McLellan, SL and Lücker, S and Eren, AM}, title = {Author Correction: Nitrogen-fixing populations of Planctomycetes and Proteobacteria are abundant in surface ocean metagenomes.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {963}, doi = {10.1038/s41564-018-0209-4}, pmid = {30042441}, issn = {2058-5276}, abstract = {In the version of this Article originally published, the surname of author Sandra M. McLellan was spelt incorrectly as 'MacLellan'. This has now been corrected. In addition, Fig. 2 was mistakenly duplicated in the Supplementary Information as Supplementary Fig. 2. This has now been replaced with the correct supplementary figure (shown below).}, } @article {pmid30042234, year = {2018}, author = {Shaffer, L}, title = {Inner Workings: Unlocking the molecular mechanisms behind our sense of touch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7641-7643}, pmid = {30042234}, issn = {1091-6490}, mesh = {Animals ; Humans ; Mechanoreceptors/*metabolism ; Moles/*physiology ; Touch Perception/*genetics ; }, } @article {pmid30042233, year = {2018}, author = {Beans, C}, title = {Science and Culture: Sentient architecture promises insight into our evolving relationship with AI.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7638-7640}, doi = {10.1073/pnas.1809390115}, pmid = {30042233}, issn = {1091-6490}, } @article {pmid30042217, year = {2018}, author = {Bailey, PSJ and Hiltunen, JK and Dieckmann, CL and Kastaniotis, AJ and Nathan, JA}, title = {Different opinion on the reported role of Poldip2 and ACSM1 in a mammalian lipoic acid salvage pathway controlling HIF-1 activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7458-E7459}, pmid = {30042217}, issn = {1091-6490}, mesh = {Animals ; Attitude ; *Hypoxia-Inducible Factor 1 ; *Thioctic Acid ; }, } @article {pmid30042216, year = {2018}, author = {Paredes, F and Lassègue, B and Williams, HC and Faidley, EA and Benavides, GA and Yeligar, SM and Griendling, KK and Darley-Usmar, V and San Martin, A}, title = {Reply to Bailey et al.: New perspectives on the novel role of the Poldip2/ACSM1 axis in a functional mammalian lipoylation salvage pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7460-E7461}, pmid = {30042216}, issn = {1091-6490}, mesh = {Animals ; *Lipoylation ; Mammals ; *Nuclear Proteins ; }, } @article {pmid30042215, year = {2018}, author = {Qiang, M and Dong, X and Zha, Z and Zuo, XK and Song, XL and Zhao, L and Yuan, C and Huang, C and Tao, P and Hu, Q and Li, WG and Hu, W and Li, J and Nie, Y and Buratto, D and Zonta, F and Ma, P and Yu, Z and Liu, L and Zhang, Y and Yang, B and Xie, J and Xu, TL and Qu, Z and Yang, G and Lerner, RA}, title = {Selection of an ASIC1a-blocking combinatorial antibody that protects cells from ischemic death.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7469-E7477}, pmid = {30042215}, issn = {1091-6490}, mesh = {Acid Sensing Ion Channel Blockers/chemistry/*pharmacology/therapeutic use ; Acid Sensing Ion Channels/*immunology ; Animals ; Apoptosis/*drug effects ; Brain/blood supply/cytology/drug effects ; Brain Infarction/*drug therapy/etiology ; CHO Cells ; Cerebral Arteries ; Cricetulus ; Disease Models, Animal ; Humans ; Hydrogen-Ion Concentration ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Targeted Therapy/methods ; Neurons/drug effects/physiology ; Single-Chain Antibodies/chemistry/*pharmacology/therapeutic use ; }, abstract = {Acid-sensing ion channels (ASICs) have emerged as important, albeit challenging therapeutic targets for pain, stroke, etc. One approach to developing therapeutic agents could involve the generation of functional antibodies against these channels. To select such antibodies, we used channels assembled in nanodiscs, such that the target ASIC1a has a configuration as close as possible to its natural state in the plasma membrane. This methodology allowed selection of functional antibodies that inhibit acid-induced opening of the channel in a dose-dependent way. In addition to regulation of pH, these antibodies block the transport of cations, including calcium, thereby preventing acid-induced cell death in vitro and in vivo. As proof of concept for the use of these antibodies to modulate ion channels in vivo, we showed that they potently protect brain cells from death after an ischemic stroke. Thus, the methodology described here should be general, thereby allowing selection of antibodies to other important ASICs, such as those involved in pain, neurodegeneration, and other conditions.}, } @article {pmid30042214, year = {2018}, author = {Wu, Y and Han, B and Li, Y and Munro, E and Odde, DJ and Griffin, EE}, title = {Rapid diffusion-state switching underlies stable cytoplasmic gradients in the Caenorhabditis elegans zygote.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {36}, pages = {E8440-E8449}, pmid = {30042214}, issn = {1091-6490}, support = {R01 GM110194/GM/NIGMS NIH HHS/United States ; R01 GM098441/GM/NIGMS NIH HHS/United States ; S10 OD018046/OD/NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/cytology/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Polarity/*physiology ; Cytoplasm/genetics/*metabolism ; *Models, Biological ; Nuclear Proteins/genetics/*metabolism ; Protein Transport/physiology ; Zygote/cytology/*metabolism ; }, abstract = {Protein concentration gradients organize cells and tissues and commonly form through diffusion away from a local source of protein. Interestingly, during the asymmetric division of the Caenorhabditis elegans zygote, the RNA-binding proteins MEX-5 and PIE-1 form opposing concentration gradients in the absence of a local source. In this study, we use near-total internal reflection fluorescence (TIRF) imaging and single-particle tracking to characterize the reaction/diffusion dynamics that maintain the MEX-5 and PIE-1 gradients. Our findings suggest that both proteins interconvert between fast-diffusing and slow-diffusing states on timescales that are much shorter (seconds) than the timescale of gradient formation (minutes). The kinetics of diffusion-state switching are strongly polarized along the anterior/posterior (A/P) axis by the PAR polarity system such that fast-diffusing MEX-5 and PIE-1 particles are approximately symmetrically distributed, whereas slow-diffusing particles are highly enriched in the anterior and posterior cytoplasm, respectively. Using mathematical modeling, we show that local differences in the kinetics of diffusion-state switching can rapidly generate stable concentration gradients over a broad range of spatial and temporal scales.}, } @article {pmid30041995, year = {2018}, author = {Lenton, TM and Daines, SJ and Dyke, JG and Nicholson, AE and Wilkinson, DM and Williams, HTP}, title = {Selection for Gaia across Multiple Scales.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {633-645}, doi = {10.1016/j.tree.2018.05.006}, pmid = {30041995}, issn = {1872-8383}, abstract = {Recently postulated mechanisms and models can help explain the enduring 'Gaia' puzzle of environmental regulation mediated by life. Natural selection can produce nutrient recycling at local scales and regulation of heterogeneous environmental variables at ecosystem scales. However, global-scale environmental regulation involves a temporal and spatial decoupling of effects from actors that makes conventional evolutionary explanations problematic. Instead, global regulation can emerge by a process of 'sequential selection' in which systems that destabilize their environment are short-lived and result in extinctions and reorganizations until a stable attractor is found. Such persistence-enhancing properties can in turn increase the likelihood of acquiring further persistence-enhancing properties through 'selection by survival alone'. Thus, Earth system feedbacks provide a filter for persistent combinations of macroevolutionary innovations.}, } @article {pmid30041705, year = {2018}, author = {Singh, A and Babyak, MA and Brummett, BH and Kraus, WE and Siegler, IC and Hauser, ER and Williams, RB}, title = {Developing a synthetic psychosocial stress measure and harmonizing CVD-risk data: a way forward to GxE meta- and mega-analyses.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {504}, pmid = {30041705}, issn = {1756-0500}, support = {P01 HL036587/HL/NHLBI NIH HHS/United States ; P01HL036587//National Heart, Lung, and Blood Institute/ ; }, mesh = {Demography ; Genetic Variation ; Humans ; Hypertension/*psychology ; Sample Size ; Statistics as Topic ; *Stress, Psychological ; }, abstract = {OBJECTIVES: Among many challenges in cardiovascular disease (CVD) risk prediction are interactions of genes with stress, race, and/or sex and developing robust estimates of these interactions. Improved power with larger sample size contributed by the accumulation of epidemiological data could be helpful, but integration of these datasets is difficult due the absence of standardized phenotypic measures. In this paper, we describe the details of our undertaking to harmonize a dozen datasets and provide a detailed account of a number of decisions made in the process.

RESULTS: We harmonized candidate genetic variants and CVD-risk variables related to demography, adiposity, hypertension, lipodystrophy, hypertriglyceridemia, hyperglycemia, depressive symptom, and chronic psychosocial stress from a dozen studies. Using our synthetic stress algorithm, we constructed a synthetic chronic psychosocial stress measure in nine out of twelve studies where a formal self-rated stress measure was not available. The mega-analytic partial correlation between the stress measure and depressive symptoms while controlling for the effect of study variable in the combined dataset was significant (Rho = 0.27, p < 0.0001). This evidence of the validity and the detailed account of our data harmonization approaches demonstrated that it is possible to overcome the inconsistencies in the collection and measurement of human health risk variables.}, } @article {pmid30041692, year = {2018}, author = {Nkrumah, J and Gbagbo, FY}, title = {Institutional support for breastfeeding in Ghana: a case study of University of Education, Winneba.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {501}, pmid = {30041692}, issn = {1756-0500}, mesh = {Adult ; *Breast Feeding ; Female ; Ghana ; Humans ; Infant ; Mothers ; Pregnancy ; *Students ; *Universities ; Young Adult ; }, abstract = {OBJECTIVES: This study explored institutional support for breastfeeding student-mothers in the University of Education, Winneba, Ghana. It also examined challenges associated with combining academic work with breastfeeding and childcare.

RESULTS: Findings show that although the University as an institution does not have any formal system in place to support breastfeeding among student-mothers, it does follow the provisions made for breastfeeding under the maternity protection section of the labor Act (Act, 651) for its employees. Consequently, breastfeeding student mothers use under trees, lobbies, and Junior Common Rooms of on-campus halls of residence as lactation sites which exposes their babies to risk of infection. The absence of support put student-mothers through stress, divided attention, and conflicting responsibilities between academic work and childcare. Further studies to investigate the situation on other university campuses are recommended to promote policy and interventions on breastfeeding and childcare in tertiary institutions in Ghana to enable students maintain a balance between breastfeeding, childcare and academic work.}, } @article {pmid30041689, year = {2018}, author = {Taniguchi, S and Takahashi, H and Aoki, Y and Nakajima, A and Terajima, F and Sonobe, M and Akatsu, Y and Yamada, M and Furuya, T and Koda, M and Yamazaki, M and Ohtori, S and Nakagawa, K}, title = {Surgical treatment for dropped head syndrome with cervical spondylotic amyotrophy: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {500}, pmid = {30041689}, issn = {1756-0500}, mesh = {Aged ; Cervical Vertebrae ; Humans ; Male ; Muscle Weakness ; Muscular Atrophy/*surgery ; Neck/physiopathology ; Spinal Cord Compression ; Spondylosis/*surgery ; Treatment Outcome ; }, abstract = {BACKGROUND: Dropped head syndrome (DHS) is a flexion deformity of the neck that is caused by severe weakness of the neck extensor muscles. DHS occurs in combination with not only neuromuscular disorders, but also cervical spondylosis. However, there are few reports of DHS complicated by cervical spondylotic amyotrophy (CSA). Here we report a case of DHS with CSA in a patient who underwent surgical treatment.

CASE PRESENTATION: A 79-year-old man became aware of dropped head and gait disturbance in addition to the paralysis of his right upper extremity. At his initial visit, he had a severe chin-on-chest posture. Neurological examination revealed severe paralysis of deltoid, biceps, wrist extensor, finger flexor, extensor, and abductors, in addition to lower extremity spasticity. Nevertheless, sensory dysfunction was not observed. X-ray images showed severe kyphosis at the upper thoracic level. MRI and CT myelography findings revealed spinal canal stenosis at the level of C5-6 and C6 root compression of the right side. Motor neuron disease was excluded because of findings from electromyography. Therefore, we diagnosed this patient as having DHS with cervical spondylotic amyotrophy. A C2-Th5 posterior fusion with C3-C6 laminoplasty and C5-6 foraminotomy on the right side were performed. After surgery, the complaint of dropped head was improved significantly and bilaterally finger motion was improved slightly. His neck position was maintained at the final follow-up at about 1 year after surgery.

CONCLUSIONS: Despite the limitation of short-term follow-up, favorable results for the DHS were maintained in the present case. Surgical treatment for similar cases may be a feasible option, but surgery does have some complications.}, } @article {pmid30041687, year = {2018}, author = {Solomon, FB and Wada, FW and Anjulo, AA and Koyra, HC and Tufa, EG}, title = {Burden of intestinal pathogens and associated factors among asymptomatic food handlers in South Ethiopia: emphasis on salmonellosis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {502}, pmid = {30041687}, issn = {1756-0500}, support = {123/2016//Wolaita sodo university/ ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Cross-Sectional Studies ; Ethiopia ; *Food Handling ; Humans ; Meat ; Parasitic Diseases/*epidemiology ; Prevalence ; Salmonella/isolation & purification ; Salmonella Food Poisoning ; Salmonella Infections/*epidemiology ; }, abstract = {OBJECTIVE: The study aims to assess the burden of intestinal parasites and Salmonellosis among asymptomatic food handlers at meal serving facilities in Sodo town. Antibiotic resistance was also common and increasing among Salmonella isolates with multidrug resistance as current concern.

RESULT: Community based cross-sectional study was carried out from 387 food handlers working in meal serving facilities. Food handlers, 159(41%) had one or more intestinal parasites. A. lumbricoides was the most prevalent parasite 30(7.8%), followed by Taenia species 26(6.7%) and Hook worm 23(5.9%). A total number of 35 Salmonella isolates were found of which Sero-group D was the most frequent, 17(48.5%) followed by Sero-group C, 12(34.3%), and B 6(17.1%). Ten (2.5%) isolates were Salmonella typhi. Raw meat eating, hand washing after toilet and after touching dirty materials showed significant association with intestinal pathogens. Salmonella isolates were highly resistant to ampicillin (85.7%), amoxicillin and tetracycline 74.3% each. Multidrug resistance prevalence of 81.8% was identified. Periodic screening of food handlers is important in order to prevent the transmission of intestinal parasites and Salmonellosis. Treatment needs to be based on accurate laboratory detection to mitigate the spread of drug resistant Salmonella strains.}, } @article {pmid30041686, year = {2018}, author = {Paulander, W and Varming, AN and Bojer, MS and Friberg, C and Bæk, K and Ingmer, H}, title = {The agr quorum sensing system in Staphylococcus aureus cells mediates death of sub-population.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {503}, pmid = {30041686}, issn = {1756-0500}, support = {12-127417//Teknologi og Produktion, Det Frie Forskningsråd (DK)/ ; 09-076146//Teknologi og Produktion, Det Frie Forskningsråd (DK)/ ; DNRF120//Danmarks Grundforskningsfond/ ; }, mesh = {Bacterial Proteins ; *Cell Death ; *Gene Expression Regulation, Bacterial ; Humans ; *Quorum Sensing ; RNA, Bacterial/metabolism ; Staphylococcus aureus/*pathogenicity ; Trans-Activators ; Virulence ; }, abstract = {OBJECTIVE: In the human pathogen, Staphylococcus aureus, the agr quorum sensing system controls expression of a multitude of virulence factors and yet, agr negative cells frequently arise both in the laboratory and in some infections. The aim of this study was to examine the possible reasons behind this phenomenon.

RESULTS: We examined viability of wild type and agr mutant cell cultures using a live-dead stain and observed that in stationary phase, 3% of the wild type population became non-viable whereas for agr mutant cells non-viable cells were barely detectable. The effect appears to be mediated by RNAIII, the effector molecule of agr, as ectopic overexpression of RNAIII resulted in 60% of the population becoming non-viable. This effect was not due to toxicity from delta toxin that is encoded by the hld gene located within RNAIII as hld overexpression did not cause cell death. Importantly, lysed S. aureus cells promoted bacterial growth. Our data suggest that RNAIII mediated cell death of agr positive but not agr negative cells provides a selective advantage to the agr negative cell population and may contribute to the common appearance of agr negative cells in S. aureus populations.}, } @article {pmid30041622, year = {2018}, author = {Sun, H and Hu, M and Li, J and Chen, L and Li, M and Zhang, S and Zhang, X and Yang, X}, title = {Comprehensive analysis of NAC transcription factors uncovers their roles during fiber development and stress response in cotton.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {150}, pmid = {30041622}, issn = {1471-2229}, support = {2016YFD0101006//National Key Project of Research and the Development Plan/ ; 2662016PY001//Fundamental Research Funds for the Central Universities/ ; }, abstract = {BACKGROUND: Transcription factors operate as important switches of transcription networks, and NAC (NAM, ATAF, and CUC) transcription factors are a plant-specific family involved in multiple biological processes. However, this gene family has not been systematically characterized in cotton.

RESULTS: Here we identify a large number of genes with conservative NAC domains in four cotton species, with 147 found in Gossypium arboreum, 149 in G. raimondii, 267 in G. barbadense and 283 in G. hirsutum. Predicted membrane-bound NAC genes were also identified. Phylogenetic analysis showed that cotton NAC proteins clustered into seven subfamilies and homologous protein pairs showed similar characteristics. Evolutionary property analysis revealed that purifying selection of NAC genes occurred between diploid and polyploid cotton species, and variation analysis showed GhNAC genes may have been subjected to selection and domestication. NAC proteins showed extensive transactivation and this was dependent on the C-terminus. Some development and stress related cis-elements were enriched in the promoters of GhNAC genes. Comprehensive expression analysis indicated that 38 GhNAC genes were candidates for involvement in fiber development, and 120 in stress responses. Gene co-expression network analysis revealed relationships between fiber-associated NAC genes and secondary cell wall (SCW) biosynthesis genes.

CONCLUSIONS: NAC genes were identified in diploid and tetraploid cotton, revealing new insights into their evolution, variation and homology relationships. Transcriptome analysis and co-expression network indicated roles for GhNAC genes in cotton fiber development and stress response, and NAC genes may prove useful in molecular breeding programmes.}, } @article {pmid30041609, year = {2018}, author = {Yang, Z and Liu, D and Ji, H}, title = {Sucrose metabolism in developing oil-rich tubers of Cyperus esculentus: comparative transcriptome analysis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {151}, pmid = {30041609}, issn = {1471-2229}, support = {5151001//Natural Science Foundation of Beijing Municipality/ ; 31371692//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Cyperus esculentus is unique in that it can accumulate significant amounts of oil, starch and sugar as major storage reserves in tubers with high tuber yield and therefore considered as a novel model to study carbon allocation into different storage reserves in underground sink tissues such as tubers and roots. Sucrose (Suc) plays a central role in control of carbon flux toward biosynthesis of different storage reserves; however, it remains unclear for the molecular mechanism underlying Suc metabolism in underground oil-rich storage tissues. In the present study, a comprehensive transcriptome analysis of C. esculentus oil tuber compared to other plant oil- or carbohydrate-rich storage tissues was made for the expression patterns of genes related to the Suc metabolism.

RESULTS: The results revealed some species-specific features of gene transcripts in oil tuber of C. esculentus, indicating that: (i) the expressions of genes responsible for Suc metabolism are developmentally regulated and displayed a pattern dissimilar to other plant storage tissues; (ii) both of Suc breakdown and biosynthesis processes might be the major pathways associated with Suc metabolism; (iii) it was probably that Suc degradation could be primarily through the action of Suc synthase (SUS) other than invertase (INV) during tuber development. The orthologs of SUS1, SUS3 and SUS4 are the main SUS isoforms catalyzing Suc breakdown while the vacuolar INV (VIN) is the leading determinant controlling sugar composition; (iv) cytosolic hexose phosphorylation possibly relies more on fructose as substrate and uridine diphosphate glucose pyrophosphorylase (UGP) plays an important role in this pathway; (v) it is Suc-phosphate synthase (SPS) B- and C-family members rather than SPS A that are the principal contributors to SPS enzymes and play crucial roles in Suc biosynthesis pathway.

CONCLUSIONS: We have successfully identified the Suc metabolic pathways in C. esculentus tubers, highlighting several conserved and distinct expressions that might contribute to sugar accumulation in this unique underground storage tissue. The specific and differential expression genes revealed in this study might indicate the special molecular mechanism and transcriptional regulation of Suc metabolism occurred in oil tubers of C. esculentus.}, } @article {pmid30041604, year = {2018}, author = {Chen, J and Tang, X and Ren, C and Wei, B and Wu, Y and Wu, Q and Pei, J}, title = {Full-length transcriptome sequences and the identification of putative genes for flavonoid biosynthesis in safflower.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {548}, pmid = {30041604}, issn = {1471-2164}, support = {81573544//National Natural Science Foundation of China/ ; 2014SZ0156//Sichuan Science and Technology Support Program/ ; ZRYY1610, ZRQN1647//Chengdu University of Traditional Chinese Medicine Fund/ ; 203638//China Postdoctoral Science Foundation/ ; }, mesh = {Acetates/pharmacology ; Biosynthetic Pathways/genetics ; Carthamus tinctorius/drug effects/*genetics/metabolism ; Cyclopentanes/pharmacology ; Flavonoids/*biosynthesis ; Gene Expression Profiling ; Gene Ontology ; Genes, Plant ; Microsatellite Repeats ; Oxylipins/pharmacology ; RNA, Long Noncoding/chemistry ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: The flower of the safflower (Carthamus tinctorius L.) has been widely used in traditional Chinese medicine for the ability to improve cerebral blood flow. Flavonoids are the primary bioactive components in safflower, and their biosynthesis has attracted widespread interest. Previous studies mostly used second-generation sequencing platforms to survey the putative flavonoid biosynthesis genes. For a better understanding of transcription data and the putative genes involved in flavonoid biosynthesis in safflower, we carry our study.

RESULTS: High-quality RNA was extracted from six types of safflower tissue. The RNAs of different tissues were mixed equally and used for multiple size-fractionated libraries (1-2, 2-3 and 3-6 k) library construction. Five cells were carried (2 cells for 1-2 and for 2-3 k libraries and 1 cell for 3-6 k libraries). 10.43Gb clean data and 38,302 de-redundant sequences were captured. 44 unique isoforms were annotated as encoding enzymes involved in flavonoid biosynthesis. The full length flavonoid genes were characterized and their evolutional relationship and expressional pattern were analyzed. They can be divided into eight families, with a large differences in the tissue expression. The temporal expressions under MeJA treatment were also measured, 9 genes are significantly up-regulated and 2 genes are significantly down-regulated. The genes involved in flavonoid synthesis in safflower were predicted in our study. Besides, the SSR and lncRNA are also analyzed in our study.

CONCLUSIONS: Full-length transcriptome sequences were used in our study. The genes involved in flavonoid synthesis in safflower were predicted in our study. Combined the determination of flavonoids, CtC4H2, CtCHS3, CtCHI3, CtF3H3, CtF3H1 are mainly participated in MeJA promoting the synthesis of flavonoids. Our results also provide a valuable resource for further study on safflower.}, } @article {pmid30041601, year = {2018}, author = {Chen, C and Zheng, Y and Zhong, Y and Wu, Y and Li, Z and Xu, LA and Xu, M}, title = {Transcriptome analysis and identification of genes related to terpenoid biosynthesis in Cinnamomum camphora.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {550}, pmid = {30041601}, issn = {1471-2164}, support = {31460209//National Natural Science Foundation of China/ ; 2016512701//Special finance project of Jiangxi Academy of Forestry/ ; }, mesh = {Biosynthetic Pathways/genetics ; Cinnamomum camphora/chemistry/*genetics/metabolism ; Gene Expression Profiling ; Genes, Plant ; Plant Leaves/chemistry/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; Terpenes/analysis/*metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Cinnamomum camphora has been cultivated as an economically important tree for its medicinal and aromatic properties. Selective breeding has produced Cinnamomum plants for special uses, including spice strains with characteristic flavors and aromas and high-potency medicinal cultivars. The molecular biology underlying terpenoid biosynthesis is still unexplored.

RESULTS: Gas chromatography-mass spectrometry was used to analyze the differences in contents and compositions of essential oil terpenoids in linalool- and borneol-type chemotypes of C. camphora. The data revealed that the essential oils consist primarily of monoterpenes with only very minor quantities of sesquiterpenes and diterpenes and that the essential oil differs in different chemotypes of C. camphora, with higher yields of (-)-borneol from the borneol-type than from the linalool-type. To study the terpenoid biosynthesis of signature compounds of the major monoterpenes, we performed RNA sequencing to profile the leaf transcriptomes of the two chemotypes of C. camphora. A total of 23.76 Gb clean data was generated from two chemotypes and assembled into 156,184 unigenes. The total length, average length, N50 and GC content of unigenes were 155,645,929 bp, 997 bp, 1430 bp, and 46.5%, respectively. Among them, 76,421 unigenes were annotated by publicly available databases, of which 67 candidate unigenes were identified to be involved in terpenoid biosynthesis in C. camphora. A total of 2863 unigenes were identified to be differentially expression between borneol-type and linalool-type, including 1714 up-regulated and 1149 down-regulated unigenes. Most genes encoding proteins involved in terpenoid precursor MVA and MEP pathways were expressed in similar levels in both chemotypes of C. camphora. In addition, 10 and 17 DEGs were significantly enriched in the terpene synthase activity and oxidoreductase activity terms of their directed acyclic graphs (DAG), respectively. Three monoterpene synthase genes, TPS14-like1, TPS14-like2 and TPS14-like3 were up-regulated in the borneol-type compared to the linalool-type, and their expression levels were further verified using quantitative real-time PCR.

CONCLUSIONS: This study provides a global overview of gene expression patterns related to terpenoid biosynthesis in C. camphora, and could contribute to a better understanding of the differential accumulation of terpenoids in different C. camphora chemotypes.}, } @article {pmid30041597, year = {2018}, author = {Yasuda, J and Katsuoka, F and Danjoh, I and Kawai, Y and Kojima, K and Nagasaki, M and Saito, S and Yamaguchi-Kabata, Y and Tadaka, S and Motoike, IN and Kumada, K and Sakurai-Yageta, M and Tanabe, O and Fuse, N and Tamiya, G and Higasa, K and Matsuda, F and Yasuda, N and Iwasaki, M and Sasaki, M and Shimizu, A and Kinoshita, K and Yamamoto, M}, title = {Regional genetic differences among Japanese populations and performance of genotype imputation using whole-genome reference panel of the Tohoku Medical Megabank Project.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {551}, pmid = {30041597}, issn = {1471-2164}, support = {JP17km0105001, JP17km0105002, JP17km0405001//Japan Agency for Medical Research and Development/ ; }, mesh = {Asian Continental Ancestry Group/*genetics ; *Genome, Human ; Genotype ; Humans ; Japan ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Genotype imputation from single-nucleotide polymorphism (SNP) genotype data using a haplotype reference panel consisting of thousands of unrelated individuals from populations of interest can help to identify strongly associated variants in genome-wide association studies. The Tohoku Medical Megabank (TMM) project was established to support the development of precision medicine, together with the whole-genome sequencing of 1070 human genomes from individuals in the Miyagi region (Northeast Japan) and the construction of the 1070 Japanese genome reference panel (1KJPN). Here, we investigated the performance of 1KJPN for genotype imputation of Japanese samples not included in the TMM project and compared it with other population reference panels.

RESULTS: We found that the 1KJPN population was more similar to other Japanese populations, Nagahama (south-central Japan) and Aki (Shikoku Island), than to East Asian populations in the 1000 Genomes Project other than JPT, suggesting that the large-scale collection (more than 1000) of Japanese genomes from the Miyagi region covered many of the genetic variations of Japanese in mainland Japan. Moreover, 1KJPN outperformed the phase 3 reference panel of the 1000 Genomes Project (1KGPp3) for Japanese samples, and IKJPN showed similar imputation rates for the TMM and other Japanese samples for SNPs with minor allele frequencies (MAFs) higher than 1%.

CONCLUSIONS: 1KJPN covered most of the variants found in the samples from areas of the Japanese mainland outside the Miyagi region, implying 1KJPN is representative of the Japanese population's genomes. 1KJPN and successive reference panels are useful genome reference panels for the mainland Japanese population. Importantly, the addition of whole genome sequences not included in the 1KJPN panel improved imputation efficiencies for SNPs with MAFs under 1% for samples from most regions of the Japanese archipelago.}, } @article {pmid30041596, year = {2018}, author = {Rahmati Ishka, M and Brown, E and Weigand, C and Tillett, RL and Schlauch, KA and Miller, G and Harper, JF}, title = {A comparison of heat-stress transcriptome changes between wild-type Arabidopsis pollen and a heat-sensitive mutant harboring a knockout of cyclic nucleotide-gated cation channel 16 (cngc16).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {549}, pmid = {30041596}, issn = {1471-2164}, support = {P20 GM103440/GM/NIGMS NIH HHS/United States ; IS-4652-13//United States - Israel Binational Agricultural Research and Development Fund/ ; 1656774//Division of Integrative Organismal Systems/ ; GM103440//National Institute of General Medical Sciences/ ; NEV00384//University of Nevada, Reno (US) College of Agriculture Biotechnology and Natural Resources HATCH/ ; }, mesh = {Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics ; Calcium Signaling/genetics ; Cyclic Nucleotide-Gated Cation Channels/*genetics ; Gene Knockout Techniques ; Heat-Shock Response/*genetics ; Pollen/*genetics/metabolism ; Transcription Factors/genetics/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: In flowering plants, the male gametophyte (pollen) is one of the most vulnerable cells to temperature stress. In Arabidopsis thaliana, a pollen-specific Cyclic Nucleotide-Gated cation Channel 16 (cngc16), is required for plant reproduction under temperature-stress conditions. Plants harboring a cncg16 knockout are nearly sterile under conditions of hot days and cold nights. To understand the underlying cause, RNA-Seq was used to compare the pollen transcriptomes of wild type (WT) and cngc16 under normal and heat stress (HS) conditions.

RESULTS: Here we show that a heat-stress response (HSR) in WT pollen resulted in 2102 statistically significant transcriptome changes (≥ 2-fold changes with adjusted p-value ≤0.01), representing approximately 15% of 14,226 quantified transcripts. Of these changes, 89 corresponded to transcription factors, with 27 showing a preferential expression in pollen over seedling tissues. In contrast to WT, cngc16 pollen showed 1.9-fold more HS-dependent changes (3936 total, with 2776 differences between WT and cngc16). In a quantitative direct comparison between WT and cngc16 transcriptomes, the number of statistically significant differences increased from 21 pre-existing differences under normal conditions to 192 differences under HS. Of the 20 HS-dependent changes in WT that were most different in cngc16, half corresponded to genes encoding proteins predicted to impact cell wall features or membrane dynamics.

CONCLUSIONS: Results here define an extensive HS-dependent reprogramming of approximately 15% of the WT pollen transcriptome, and identify at least 27 transcription factor changes that could provide unique contributions to a pollen HSR. The number of statistically significant transcriptome differences between WT and cngc16 increased by more than 9-fold under HS, with most of the largest magnitude changes having the potential to specifically impact cell walls or membrane dynamics, and thereby potentiate cngc16 pollen to be hypersensitive to HS. However, HS-hypersensitivity could also be caused by the extensive number of differences throughout the transcriptome having a cumulative effect on multiple cellular pathways required for tip growth and fertilization. Regardless, results here support a model in which a functional HS-dependent reprogramming of the pollen transcriptome requires a specific calcium-permeable Cyclic Nucleotide-Gated cation Channel, CNGC16.}, } @article {pmid30041083, year = {2018}, author = {Gonze, D and Coyte, KZ and Lahti, L and Faust, K}, title = {Microbial communities as dynamical systems.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {41-49}, doi = {10.1016/j.mib.2018.07.004}, pmid = {30041083}, issn = {1879-0364}, abstract = {Nowadays, microbial communities are frequently monitored over long periods of time and the interactions between their members are explored in vitro. This development has opened the way to apply mathematical models to characterize community structure and dynamics, to predict responses to perturbations and to explore general dynamical properties such as stability, alternative stable states and periodicity. Here, we highlight the role of dynamical systems theory in the exploration of microbial communities, with a special emphasis on the generalized Lotka-Volterra (gLV) equations. In particular, we discuss applications, assumptions and limitations of the gLV model, mention modifications to address these limitations and review stochastic extensions. The development of dynamical models, together with the generation of time series data, can improve the design and control of microbial communities.}, } @article {pmid30041026, year = {2018}, author = {Bogarín, D and Pérez-Escobar, OA and Groenenberg, D and Holland, SD and Karremans, AP and Lemmon, EM and Lemmon, AR and Pupulin, F and Smets, E and Gravendeel, B}, title = {Anchored hybrid enrichment generated nuclear, plastid and mitochondrial markers resolve the Lepanthes horrida (Orchidaceae: Pleurothallidinae) species complex.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {27-47}, doi = {10.1016/j.ympev.2018.07.014}, pmid = {30041026}, issn = {1095-9513}, abstract = {Phylogenetic relationships in species complexes and lineages derived from rapid diversifications are often challenging to resolve using morphology or standard DNA barcoding markers. The hyper-diverse genus Lepanthes from Neotropical cloud forest includes over 1200 species and many recent, explosive diversifications that have resulted in poorly supported nodes and morphological convergence across clades. Here, we assess the performance of 446 nuclear-plastid-mitochondrial markers derived from an anchored hybrid enrichment approach (AHE) coupled with coalescence- and species network-based inferences to resolve phylogenetic relationships and improve species recognition in the Lepanthes horrida species group. In addition to using orchid-specific probes to increase enrichment efficiency, we improved gene tree resolution by extending standard angiosperm targets into adjacent exons. We found high topological discordance among individual gene trees, suggesting that hybridization/polyploidy may have promoted speciation in the lineage via formation of new hybrid taxa. In addition, we identified ten loci with the highest phylogenetic informativeness values from these genomes. Most previous phylogenetic sampling in the Pleurothallidinae relies on two regions (ITS and matK), therefore, the evaluation of other markers such as those shown here may be useful in future phylogenetic studies in the orchid family. Coalescent-based species tree estimation methods resolved the phylogenetic relationships of the L. horrida species group. The resolution of the phylogenetic estimations was improved with the inclusion of extended anchor targets. This approach produced longer loci with higher discriminative power. These analyses also disclosed two undescribed species, L. amicitiae and L. genetoapophantica, formally described here, which are also supported by morphology. Our study demonstrates the utility of combined genomic evidence to disentangle phylogenetic relationships at very shallow levels of the tree of life, and in clades showing convergent trait evolution. With a fully resolved phylogeny, is it possible to disentangle traits evolving in parallel or convergently across these orchid lineages such as flower color and size from diagnostic traits such as the shape and orientation of the lobes of the petals and lip.}, } @article {pmid30040922, year = {2018}, author = {Naumann, B and Englert, C}, title = {Dispersion/reaggregation in early development of annual killifishes: Phylogenetic distribution and evolutionary significance of a unique feature.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {69-79}, doi = {10.1016/j.ydbio.2018.07.015}, pmid = {30040922}, issn = {1095-564X}, mesh = {Adaptation, Physiological ; Animals ; Blastomeres/physiology ; Cell Differentiation/genetics/physiology ; Diapause/genetics/*physiology ; Embryo, Nonmammalian/metabolism ; Embryonic Development/physiology ; Fundulidae/genetics/growth & development ; Gastrulation/physiology ; Killifishes/*genetics/*growth & development/physiology ; Phylogeny ; }, abstract = {Annual killifishes are members of the Aplocheiloidea and live in ephemeral habitats that desiccate regularly during the dry season and refill during the rainy season. Populations of these fishes survive the dry season by producing drought-resistant diapausing eggs that are buried in the substrate. When the pool refills during the rainy season the juveniles hatch, grow rapidly and reproduce until the pool desiccates again during the next dry season. The association with such unpredictable habitats has led to the evolution to a variety of developmental adaptations such as a dispersed/reaggregation phase of the deep blastomeres, three possible diapause stages, extreme tolerance to high salinity and anoxia, an efficient DNA repair system and an extremely short life span. Here, we review the course of the dispersed/reaggregation phase, its evolution and phylogenetic distribution and diversity within the Aplocheiloidea. The phenomenon of blastomere dispersion/reaggregation in these fishes was first described in the 1960s and 70s. Blastomeres of most teleost fishes segregate into three groups that give rise to the enveloping cell layer, the yolk syncytial layer and the deep blastomeres that will form the embryo itself. When epiboly commences, the deep blastomeres form a more or less coherent cell sheet with a so called embryonic shield at it marginal zone marking the area where gastrulation takes place. In annual killifishes, the deep blastomeres segregate when epiboly starts and disperse when epiboly commences. After epiboly has been completed, the deep blastomeres are randomly distributed and migrate all over the enveloping cell layer. After several days they start to reaggregate and form the actual embryo that starts gastrulation. The evolutionary origin and mechanism behind this peculiar developmental pathway have puzzled developmental biologists for almost 50 years. However, several of these annual killifishes (Nothobranchius furzeri, Austrofundulus limnaeus, Austrolebias charrua and Austrolebias bellottii) have become model organisms in studies on developmental physiology, aging and stress tolerance. This has led to the establishment of modern genetic techniques such as transgenesis and cell fate mapping that are now used to tackle questions about the origin and mechanisms behind the dispersal/reaggregation phase.}, } @article {pmid30040114, year = {2018}, author = {Letsch, H and Gottsberger, B and Metzl, C and Astrin, J and Friedman, ALL and McKenna, DD and Fiedler, K}, title = {Climate and host-plant associations shaped the evolution of ceutorhynch weevils throughout the Cenozoic.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1815-1828}, pmid = {30040114}, issn = {1558-5646}, support = {DEB1355169//National Science Foundation/ ; }, abstract = {Using molecular phylogenetic data and methods we inferred divergence times and diversification patterns for the weevil subfamily Ceutorhynchinae in the context of host-plant associations and global climate over evolutionary time. We detected four major diversification shifts that correlate with both host shifts and major climate events. Ceutorhynchinae experienced an increase in diversification rate at ∼53 Ma, during the Early Eocene Climate Optimum, coincident with a host shift to Lamiaceae. A second major diversification phase occurred at the end of the Eocene (∼34 Ma). This contrasts with the overall deterioration in climate equability at the Eocene-Oligocene boundary, but tracks the diversification of important host plant clades in temperate (higher) latitudes, leading to increased diversification rates in the weevil clades infesting temperate hosts. A third major phase of diversification is correlated with the rising temperatures of the Late Oligocene Warming Event (∼26.5 Ma); diversification rates then declined shortly after the Middle Miocene Climate Transition (∼14.9 Ma). Our results indicate that biotic and abiotic factors together explain the evolution of Ceutorhynchinae better than each of these drivers viewed in isolation.}, } @article {pmid30040064, year = {2018}, author = {Liu, H and Ren, L and Lu, P and Sun, L and Zhu, G}, title = {Arenimonas caeni sp. nov., isolated from activated sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2996-3000}, doi = {10.1099/ijsem.0.002937}, pmid = {30040064}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Ubiquinone/chemistry ; Xanthomonadaceae/*classification/genetics/isolation & purification ; }, abstract = {A Gram-stain-negative, non-spore-forming, motile and rod-shaped strain, z29T, was isolated from the active sludge of a municipal wastewater treatment plant at Wuhu, Anhui, PR China. Phylogenetic analysis of the 16S rRNA gene revealed that strain z29T is most closely related to the genus Arenimonas, showing the highest similarity to Arenimonas donghaensis HO3-R19T (97.14 %), Arenimonas aestuarii S2-21T (96.46 %), Arenimonas daejeonensis T7-07T (96.24 %) and Arenimonas taoyuanensis YN2-31AT (96.23 %). The only respiratory quinone of strain z29T was ubiquinone 8 (Q-8). The major cellular fatty acids (>10 %) were iso-C15 : 0, iso-C16 : 0 and summed feature 9 (iso-C17 : 1ω9c and/or C16 : 010-methyl). The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The genomic DNA G+C content was 70.2 mol%. Genomic comparison between strain z29T and Arenimonas donghaensis HO3-R19T revealed 83.72 % average nucleotide identity. Based on the phenotypic and chemotaxonomic results together with phylogenetical analysis, strain z29T is classified as representing a novel species of the genus Arenimonas, for which the name Arenimonas caeni sp. nov. is proposed. The type strain is z29T (=JCM 32091T=CCTCC AB 2017067T).}, } @article {pmid30040062, year = {2018}, author = {Lee, DW and Lee, H and Kwon, BO and Khim, JS and Yim, UH and Park, H and Park, B and Choi, IG and Kim, BS and Kim, JJ}, title = {Oceanimonas marisflavi sp. nov., a polycyclic aromatic hydrocarbon-degrading marine bacterium.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2990-2995}, doi = {10.1099/ijsem.0.002932}, pmid = {30040062}, issn = {1466-5034}, mesh = {Aeromonadaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/microbiology ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; Polycyclic Aromatic Hydrocarbons/*metabolism ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, strictly aerobic, motile and rod-shaped bacterial strain, designated 102-Na3T, was isolated from sediment of Sinduri beach in Taean, Republic of Korea. Strain 102-Na3T grew optimally at 28-37 °C, at pH 7.0-11.0 and in the presence of 1-3 % (w/v) NaCl, but NaCl was not an absolute requirement for growth. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain 102-Na3T joined the clade comprising the type strains of Oceanimonasspecies. Strain 102-Na3T exhibited 16S rRNA gene sequence similarity values of 98.8, 98.3 and 98.0 % to the type strains of Oceanimonas doudoroffii MBIC1298T, Oceanimonas baumannii GB6T and Oceanimonas smirnovii 31-13T, respectively. Strain 102-Na3T contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0 and C12 : 0 as major fatty acids. The major quinone was ubiquinone-8. The polar lipids were composed of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and two unidentified amino lipids. The DNA G+C content was 56.8 mol%. Strain 102-Na3T exhibited DNA-DNA relatedness values of 25.7, 21.7 and 14.8 % to the type strains of O. doudoroffii, O. baumannii and O. smirnovii, respectively. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain 102-Na3T is separated from recognized species of the genus Oceanimonas. On the basis of the data presented, strain 102-Na3T (=KCTC 62271T=JCM 32358T=DSM 106032T) is considered the type strain of a novel species of the genus Oceanimonas, for which the name Oceanimonas marisflavi sp. nov. is proposed.}, } @article {pmid30040061, year = {2018}, author = {Chanama, S and Janphen, S and Suriyachadkun, C and Chanama, M}, title = {Pseudonocardia mangrovi sp. nov., isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2949-2955}, doi = {10.1099/ijsem.0.002927}, pmid = {30040061}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Avicennia/microbiology ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; *Wetlands ; }, abstract = {A novel Gram-stain-positive, aerobic actinomycete, designated strain SMC 195T, was isolated from soil collected from a mangrove forest in Thailand. The strain produced extensively branched substrate and aerial mycelia. The substrate mycelium was fragmented into rod-shaped elements, and spore chains consisting of smooth and rod-shaped spores were formed on the aerial mycelium. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that SMC 195T represented a member of the genus Pseudonocardia, and the most closely phylogenetically related species were Pseudonocardia yuanmonensisJCM 18055T (99.2 % 16S rRNA gene sequence similarity), Pseudonocardia halophobicaNRRL B-16514T (98.9 %) and Pseudonocardia kujensisNRRL B-24890T (98.7 %). However, the DNA-DNA relatedness values between SMC 195Tand the closest phylogenetically related species were significantly below 70 %. The G+C content of the genomic DNA was 74±0.8 mol%. The cell wall peptidoglycan contained meso-diaminopimelic acid. The whole-cell sugars consisted of arabinose, galactose, glucose, rhamnose and ribose. The menaquinone was MK-8(H4) only. The major cellular fatty acid was the branched fatty acid iso-C16 : 0 (33.6 %). The polar lipids detected were phosphatidylethanolamine, phosphatidylmethylethanolamine, hydroxyphosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol and unidentified glycolipids. On the basis of the results from phenotypic, chemotaxonomic and genotypic studies, it is concluded that SMC 195T represents a novel species of the genus Pseudonocardia, for which the name Pseudonocardia mangrovi sp. nov. is proposed. The type strain is SMC 195T (=TBRC 7778T=NBRC 113150T).}, } @article {pmid30039868, year = {2018}, author = {Blaimer, BB and Mawdsley, JR and Brady, SG}, title = {Multiple origins of sexual dichromatism and aposematism within large carpenter bees.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1874-1889}, doi = {10.1111/evo.13558}, pmid = {30039868}, issn = {1558-5646}, support = {Hatch project 1015782//National Institute of Food and Agriculture/ ; 1555905//Directorate for Biological Sciences/ ; //Global Genome Initiative/ ; //National Science Foundation/ ; //United States Department of Agriculture/ ; }, abstract = {The evolution of reversed sexual dichromatism and aposematic coloration has long been of interest to both theoreticians and empiricists. Yet despite the potential connections between these phenomena, they have seldom been jointly studied. Large carpenter bees (genus Xylocopa) are a promising group for such comparative investigations as they are a diverse clade in which both aposematism and reversed sexual dichromatism can occur either together or separately. We investigated the evolutionary history of dichromatism and aposematism and a potential correlation of these traits with diversification rates within Xylocopa, using a newly generated phylogeny for 179 Xylocopa species based on ultraconserved elements (UCEs). A monochromatic, inconspicuous ancestor is indicated for the genus, with subsequent convergent evolution of sexual dichromatism and aposematism in multiple lineages. Aposematism is found to covary with reversed sexual dichromatism in many species; however, reversed dichromatism also evolved in non-aposematic species. Bayesian Analysis of Macroevolutionary Models (BAMM) did not show increased diversification in any specific clade in Xylocopa, whereas support from Hidden State Speciation and Extinction (HiSSE) models remained inconclusive regarding an association of increased diversification rates with dichromatism or aposematism. We discuss the evolution of color patterns and diversification in Xylocopa by considering potential drivers of dichromatism and aposematism.}, } @article {pmid30039639, year = {2018}, author = {Rodger, JG and Landi, P and Hui, C}, title = {Heterogeneity in local density allows a positive evolutionary relationship between self-fertilisation and dispersal.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1784-1800}, doi = {10.1111/evo.13562}, pmid = {30039639}, issn = {1558-5646}, support = {89967//National Research Foundation/ ; 109244//National Research Foundation/ ; 109683//National Research Foundation/ ; }, abstract = {Despite empirical evidence for a positive relationship between dispersal and self-fertilization (selfing), theoretical work predicts that these traits should always be negatively correlated, and the Good Coloniser Syndrome of high dispersal and selfing (Cf. Baker's Law) should not evolve. Critically, previous work assumes that adult density is spatiotemporally homogeneous, so selfing results in identical offspring production for all patches, eliminating the benefit of dispersal for escaping from local resource competition. We investigate the joint evolution of dispersal and selfing in a demographically structured metapopulation model where local density is spatiotemporally heterogeneous due to extinction-recolonization dynamics. Selfing alleviates outcrossing failure due to low local density (an Allee effect) while dispersal alleviates competition through dispersal of propagules from high- to low-density patches. Because local density is spatiotemporally heterogeneous in our model, selfing does not eliminate heterogeneity in competition, so dispersal remains beneficial even under full selfing. Hence the Good Coloniser Syndrome is evolutionarily stable under a broad range of conditions, and both negative and positive relationships between dispersal and selfing are possible, depending on the environment. Our model thus accommodates positive empirical relationships between dispersal and selfing not predicted by previous theoretical work and provides additional explanations for negative relationships.}, } @article {pmid30039566, year = {2018}, author = {Stayton, CT and O'Connor, LF and Nisivoccia, NM}, title = {The influence of multiple functional demands on morphological diversification: A test on turtle shells.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1933-1949}, doi = {10.1111/evo.13561}, pmid = {30039566}, issn = {1558-5646}, support = {IOS-1257142//National Science Foundation/ ; }, abstract = {Organismal parts are often involved in the performance of more than one function. The role of trade-offs in influencing phenotypic evolution of such parts is well-studied; less well-understood is their role in influencing phenotypic diversity. Increases in the number of functions a part is involved in may inhibit subsequent diversification, as the number of trade-offs increases. Alternately, such an increase might promote phenotypic diversification, by increasing adaptive landscape complexity and promoting specialization for different roles. We compare these predictions by testing whether aquatic turtle shells, which resist loads, act as hydrodynamic elements, facilitate self-righting, and exchange heat with the environment, differ in phenotypic diversity from those of terrestrial species, which perform all the same functions except for hydrodynamics. We used 53 3D landmarks digitized on 2722 specimens of 274 hard-shelled turtle species to quantify shell shape variation, and a set of phylogenetic hypotheses to examine evolutionary patterns. Terrestrial turtles consistently had higher phenotypic diversity than aquatic species. Differences are not due to differences in the rates of evolution between the two groups, but rather differences in evolutionary mode. Thus this study supports the traditional view of the role of multiple functions in determining phenotypic diversity.}, } @article {pmid30039545, year = {2018}, author = {Ibáñez, CM and Rezende, EL and Sepúlveda, RD and Avaria-Llautureo, J and Hernández, CE and Sellanes, J and Poulin, E and Pardo-Gandarillas, MC}, title = {Thorson's rule, life-history evolution, and diversification of benthic octopuses (Cephalopoda: Octopodoidea).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1829-1839}, doi = {10.1111/evo.13559}, pmid = {30039545}, issn = {1558-5646}, support = {3110152//Fondo Nacional de Desarrollo Científico y Tecnológico/ ; FB 0002-2014//CAPES/ ; }, abstract = {Here, we evaluate the so-called Thorson's rule, which posits that direct-development and larger eggs are favored toward the poles in marine organisms and whose validity been the subject of considerable debate in the literature, combining an expanded phenotypic dataset encompassing 60 species of benthic octopuses with a new molecular phylogeny. Phylogenetic reconstruction shows two clades: clade 1 including species of the families Eledonidae, Megaleledonidae, Bathypolypodidae, and Enteroctopodidae, and clade 2 including species of Octopodidae. Egg size, development mode, and all environmental variables exhibited phylogenetic signal, partly due to differences between the two clades: whereas most species in clade 1 inhabit cold and deep waters, exhibit large eggs and hatchling with holobenthic development, species from clade 2 inhabit tropical-temperate and shallow waters, evolved small eggs, and generally exhibit merobenthic development. Phylogenetic regressions show that egg size exhibits a conspicuous latitudinal cline, and that both egg size and development mode vary with water temperature. Additionally, analyses suggest that egg size is constrained by body size in lineages with holobenthic development. Taken together, results suggest that the variation in egg size and development mode across benthic octopuses is adaptive and associated with water temperature, supporting Thorson's rule in these organisms.}, } @article {pmid30039183, year = {2018}, author = {Siddiqi, MZ and Shah, S and Choi, KD and Lee, SY and Kim, SY and Im, WT}, title = {Mesorhizobium hankyongi sp. nov. Isolated from Soil of Ginseng Cultivating Field.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1453-1459}, pmid = {30039183}, issn = {1432-0991}, support = {2011-0031955//This research was supported by the project on survey and excavation of Korean indigenous species of the National Institute of Biological Resources (NIBR) under the Ministry of Environment and by the by the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Science and ICT (2011-0031955)./ ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry/metabolism ; Mesorhizobium/classification/genetics/*isolation & purification/metabolism ; Panax/*growth & development/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Soil Microbiology ; }, abstract = {A Gram-negative, non-spore-forming and rod-shaped, bacterium (designated Gsoil 531T) was isolated from soil of a ginseng field. On the basis of 16S rRNA gene sequence, strain Gsoil 531T clustered with species of the genus Mesorhizobium and was closely related to M. camelthorni CCNWXJ 40-4T (98.9%) and M. alhagi CCNWXJ12-2T (98.7%). The DNA G + C content was 62.9 mol% and the predominant quinone was ubiquinone-10 (Q-10). The major cellular fatty acids were C16:0, C19:0 cyclo ω8c and summed feature 8 (C18:1 ω7c/C18:1 ω6c). The DNA-DNA hybridization values were less than 35.0% between novel isolate and its closest reference strains M. camelthorni HAMBI 3020T, M. alhagi HAMBI 3019T and M tamadayense LMG 26736T. Physiological, biochemical and low values of DNA-DNA hybridization results enabled strain Gsoil 531T to be differentiated genotypically and phenotypically from all known species of the genus Mesorhizobium. Therefore, strain Gsoil 531T signifies a novel species of the genus Mesorhizobium, for which the name Mesorhizobium hankyongi sp. nov. is proposed. The type strain Gsoil 531T (= KACC 19443T = LMG 30463T).}, } @article {pmid30038779, year = {2018}, author = {Williams, EM and O'Donnell, CFJ and Armstrong, DP}, title = {Cost-benefit analysis of acoustic recorders as a solution to sampling challenges experienced monitoring cryptic species.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6839-6848}, pmid = {30038779}, issn = {2045-7758}, abstract = {The inferences that can be made from any study are limited by the quality of the sampling design. By bad luck, when monitoring species that are difficult to detect (cryptic), sampling designs become dictated by what is feasible rather than what is desired. We calibrated and conducted a cost-benefit analysis of four acoustic recorder options that were being considered as potential solutions to several sampling restrictions experienced while monitoring the Australasian bittern, a cryptic wetland bird. Such sampling restrictions are commonly experienced while monitoring many different endangered species, particularly those that are cryptic. The recorder options included mono and stereo devices, with two sound file processing options (visual and audible analysis). Recording devices provided call-count data similar to those collected by field observers but at a fraction of the cost, which meant that "idealistic" sampling regimes, previously thought to be too expensive, became feasible for bitterns. Our study is one of the few to assess the monetary value of recording devices in the context of data quality, allowing trade-offs (and potential solutions) commonly experienced while monitoring cryptic endangered species to be shown and compared more clearly. The ability to overcome challenges of monitoring cryptic species in this way increases research possibilities for data deficient species and is applicable to any species with similar monitoring challenges.}, } @article {pmid30038778, year = {2018}, author = {Stein, K and Stenchly, K and Coulibaly, D and Pauly, A and Dimobe, K and Steffan-Dewenter, I and Konaté, S and Goetze, D and Porembski, S and Linsenmair, KE}, title = {Impact of human disturbance on bee pollinator communities in savanna and agricultural sites in Burkina Faso, West Africa.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6827-6838}, pmid = {30038778}, issn = {2045-7758}, abstract = {All over the world, pollinators are threatened by land-use change involving degradation of seminatural habitats or conversion into agricultural land. Such disturbance often leads to lowered pollinator abundance and/or diversity, which might reduce crop yield in adjacent agricultural areas. For West Africa, changes in bee communities across disturbance gradients from savanna to agricultural land are mainly unknown. In this study, we monitored for the impact of human disturbance on bee communities in savanna and crop fields. We chose three savanna areas of varying disturbance intensity (low, medium, and high) in the South Sudanian zone of Burkina Faso, based on land-use/land cover data via Landsat images, and selected nearby cotton and sesame fields. During 21 months covering two rainy and two dry seasons in 2014 and 2015, we captured bees using pan traps. Spatial and temporal patterns of bee species abundance, richness, evenness and community structure were assessed. In total, 35,469 bee specimens were caught on 12 savanna sites and 22 fields, comprising 97 species of 32 genera. Bee abundance was highest at intermediate disturbance in the rainy season. Species richness and evenness did not differ significantly. Bee communities at medium and highly disturbed savanna sites comprised only subsets of those at low disturbed sites. An across-habitat spillover of bees (mostly abundant social bee species) from savanna into crop fields was observed during the rainy season when crops are mass-flowering, whereas most savanna plants are not in bloom. Despite disturbance intensification, our findings suggest that wild bee communities can persist in anthropogenic landscapes and that some species even benefitted disproportionally. West African areas of crop production such as for cotton and sesame may serve as important food resources for bee species in times when resources in the savanna are scarce and receive at the same time considerable pollination service.}, } @article {pmid30038777, year = {2018}, author = {Iwanycki Ahlstrand, N and Havskov Reghev, N and Markussen, B and Bruun Hansen, HC and Eiriksson, FF and Thorsteinsdóttir, M and Rønsted, N and Barnes, CJ}, title = {Untargeted metabolic profiling reveals geography as the strongest predictor of metabolic phenotypes of a cosmopolitan weed.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6812-6826}, pmid = {30038777}, issn = {2045-7758}, abstract = {Plants produce a multitude of metabolites that contribute to their fitness and survival and play a role in local adaptation to environmental conditions. The effects of environmental variation are particularly well studied within the genus Plantago; however, previous studies have largely focused on targeting specific metabolites. Studies exploring metabolome-wide changes are lacking, and the effects of natural environmental variation and herbivory on the metabolomes of plants growing in situ remain unknown. An untargeted metabolomic approach using ultra-high-performance liquid chromatography-mass spectrometry, coupled with variation partitioning, general linear mixed modeling, and network analysis was used to detect differences in metabolic phenotypes of Plantago major in fifteen natural populations across Denmark. Geographic region, distance, habitat type, phenological stage, soil parameters, light levels, and leaf area were investigated for their relative contributions to explaining differences in foliar metabolomes. Herbivory effects were further investigated by comparing metabolomes from damaged and undamaged leaves from each plant. Geographic region explained the greatest number of significant metabolic differences. Soil pH had the second largest effect, followed by habitat and leaf area, while phenological stage had no effect. No evidence of the induction of metabolic features was found between leaves damaged by herbivores compared to undamaged leaves on the same plant. Differences in metabolic phenotypes explained by geographic factors are attributed to genotypic variation and/or unmeasured environmental factors that differ at the regional level in Denmark. A small number of specialized features in the metabolome may be involved in facilitating the success of a widespread species such as Plantago major into such wide range of environmental conditions, although overall resilience in the metabolome was found in response to environmental parameters tested. Untargeted metabolomic approaches have great potential to improve our understanding of how specialized plant metabolites respond to environmental change and assist in adaptation to local conditions.}, } @article {pmid30038776, year = {2018}, author = {Hess, C and Härdtle, W and Kunz, M and Fichtner, A and von Oheimb, G}, title = {A high-resolution approach for the spatiotemporal analysis of forest canopy space using terrestrial laser scanning data.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6800-6811}, pmid = {30038776}, issn = {2045-7758}, abstract = {Forest canopies and tree crown structures are of high ecological importance. Measuring canopies and crowns by direct inventory methods is time-consuming and of limited accuracy. High-resolution inventory tools, in particular terrestrial laser scanning (TLS), is able to overcome these limitations and obtain three-dimensional (3D) structural information about the canopy with a very high level of detail. The main objective of this study was to introduce a novel method to analyze spatiotemporal dynamics in canopy occupancy at the individual tree and local neighborhood level using high-resolution 3D TLS data. For the analyses, a voxel grid approach was applied. The tree crowns were modeled through the combination of two approaches: the encasement of all crown points with a 3D α-shape, which was then converted into a voxel grid, and the direct voxelization of the crown points. We show that canopy occupancy at individual tree level can be quantified as the crown volume occupied only by the respective tree or shared with neighboring trees. At the local neighborhood level, our method enables the precise determination of the extent of canopy space filling, the identification of tree-tree interactions, and the analysis of complementary space use. Using multitemporal TLS data recordings, this method allows the precise detection and quantification of changes in canopy occupancy through time. The method is applicable to a wide range of investigations in forest ecology research, including the study of tree diversity effects on forest productivity or growing space analyses for optimal tree growth. Due to the high accuracy of this novel method, it facilitates the precise analyses even of highly plastic individual tree crowns and, thus, the realistic representation of forest canopies. Moreover, our voxel grid framework is flexible enough to allow for the inclusion of further biotic and abiotic variables relevant to complex analyses of forest canopy dynamics.}, } @article {pmid30038775, year = {2018}, author = {Murgatroyd, M and Photopoulou, T and Underhill, LG and Bouten, W and Amar, A}, title = {Where eagles soar: Fine-resolution tracking reveals the spatiotemporal use of differential soaring modes in a large raptor.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6788-6799}, pmid = {30038775}, issn = {2045-7758}, abstract = {Unlike smaller raptors, which can readily use flapping flight, large raptors are mainly restricted to soaring flight due to energetic constraints. Soaring comprises of two main strategies: thermal and orographic soaring. These soaring strategies are driven by discrete uplift sources determined by the underlying topography and meteorological conditions in an area. High-resolution GPS tracking of raptor flight allows the identification of these flight strategies and interpretation of the spatiotemporal occurrence of thermal and orographic soaring. In this study, we develop methods to identify soaring flight behaviors from high-resolution GPS tracking data of Verreaux's eagle Aquila verreauxii and analyze these data to understand the conditions that promote the use of thermal and orographic soaring. We use these findings to predict the use of soaring flight both spatially (across the landscape) and temporally (throughout the year) in two topographically contrasting regions in South Africa. We found that topography is important in determining the occurrence of soaring flight and that thermal soaring occurs in relatively flat areas which are likely to have good thermal uplift availability. The predicted use of orographic soaring was predominately determined by terrain slope. Contrary to our expectations, the topography and meteorology of eagle territories in the Sandveld promoted the use of soaring flight to a greater extent than in territories in the more mountainous Cederberg region. Spatiotemporal mapping of predicted flight behaviors can broaden our understanding of how large raptors like the Verreaux's eagle use their habitat and how that links to energetics (as the preferential use of areas that maximize net energy gain is expected), reproductive success, and ultimately population dynamics. Understanding the fine-scale landscape use and environmental drivers of raptor flight can also help to predict and mitigate potential detrimental effects of anthropogenic developments, such as mortality via collision with wind turbines.}, } @article {pmid30038774, year = {2018}, author = {Wagner, TC and Richter, J and Joubert, DF and Fischer, C}, title = {A dominance shift in arid savanna: An herbaceous legume outcompetes local C4 grasses.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6779-6787}, pmid = {30038774}, issn = {2045-7758}, abstract = {The characteristic vegetation structure of arid savannas with a dominant layer of perennial grass is maintained by the putative competitive superiority of the C4 grasses. When this competitive balance is disturbed by weakening the grasses or favoring the recruitment of other species, trees, shrubs, single grass, or forb species can increase and initiate sudden dominance shifts. Such shifts involving woody species, often termed "shrub encroachment", or the mass spreading of so-called increaser species have been extensively researched, but studies on similar processes without obvious preceding disturbance are rare. In Namibia, the native herbaceous legume Crotalaria podocarpa has recently encroached parts of the escarpment region, seriously affecting the productivity of local fodder grasses. Here, we studied the interaction between seedlings of the legume and the dominant local fodder grass (Stipagrostis ciliata). We used a pot experiment to test seedling survival and to investigate the growth of Crotalaria in competition with Stipagrostis. Additional field observations were conducted to quantify the interactive effect. We found germination and growth of the legume seedlings to be facilitated by inactive (dead or dormant) grass tussocks and unhindered by active ones. Seedling survival was three times higher in inactive tussocks and Crotalaria grew taller. In the field, high densities of the legume had a clear negative effect on productivity of the grass. The C4 grass was unable to limit the recruitment and spread of the legume, and Crotalaria did outcompete the putative more competitive grass. Hence, the legume is able to spread and establish itself in large numbers and initiate a dominance shift in savannas, similar to shrub encroachment.}, } @article {pmid30038773, year = {2018}, author = {D'Amore, DC and Clulow, S and Doody, JS and Rhind, D and McHenry, CR}, title = {Claw morphometrics in monitor lizards: Variable substrate and habitat use correlate to shape diversity within a predator guild.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6766-6778}, pmid = {30038773}, issn = {2045-7758}, abstract = {Numerous studies investigate morphology in the context of habitat, and lizards have received particular attention. Substrate usage is often reflected in the morphology of characters associated with locomotion, and, as a result, claws have become well-studied ecomorphological traits linking the two. The Kimberley predator guild of Western Australia consists of 10 sympatric varanid species. The purpose of this study was to quantify claw size and shape in the guild using geometric morphometrics, and determine whether these features correlated with substrate use and habitat. Each species was assigned a Habitat/substrate group based on the substrate their claws interact with in their respective habitat. Claw morphometrics were derived for both wild caught and preserved specimens from museum collections, using a 2D semilandmark analysis. Claw shape significantly separated based on Habitat/substrate group. Varanus gouldii and Varanus panoptes claws were associated with sprinting and extensive digging. Varanus mertensi claws were for shallow excavation. The remaining species' claws reflected specialization for some form of climbing, and differed based on substrate compliance. Varanus glauerti was best adapted for climbing rough sandstone, whereas Varanus scalaris and Varanus tristis had claws ideal for puncturing wood. Phylogenetic signal also significantly influenced claw shape, with Habitat/substrate group limited to certain clades. Positive size allometry allowed for claws to cope with mass increases, and shape allometry reflected a potential size limit on climbing. Claw morphology may facilitate niche separation within this trophic guild, especially when considered with body size. As these varanids are generalist predators, morphological traits associated with locomotion may be more reliable candidates for detecting niche partitioning than those associated directly with diet.}, } @article {pmid30038772, year = {2018}, author = {Guyer, A and Hibbard, BE and Holzkämper, A and Erb, M and Robert, CAM}, title = {Influence of drought on plant performance through changes in belowground tritrophic interactions.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6756-6765}, pmid = {30038772}, issn = {2045-7758}, abstract = {Climate change is predicted to increase the risk of drought in many temperate agroecosystems. While the impact of drought on aboveground plant-herbivore-natural enemy interactions has been studied, little is known about its effects on belowground tritrophic interactions and root defense chemistry. We investigated the effects of low soil moisture on the interaction between maize, the western corn rootworm (WCR, Diabrotica virgifera), and soil-borne natural enemies of WCR. In a manipulative field experiment, reduced soil moisture and WCR attack reduced plant performance and increased benzoxazinoid levels. The negative effects of WCR on cob dry weight and silk emergence were strongest at low moisture levels. Inoculation with entomopathogenic nematodes (EPNs, Heterorhabditis bacteriophora) was ineffective in controlling WCR, and the EPNs died rapidly in the warm and dry soil. However, ants of the species Solenopsis molesta invaded the experiment, were more abundant in WCR-infested pots and predated WCR independently of soil moisture. Ant presence increased root and shoot biomass and was associated with attenuated moisture-dependent effects of WCR on maize cob weight. Our study suggests that apart from directly reducing plant performance, drought can also increase the negative effects of root herbivores such as WCR. It furthermore identifies S. molesta as a natural enemy of WCR that can protect maize plants from the negative impact of herbivory under drought stress. Robust herbivore natural enemies may play an important role in buffering the impact of climate change on plant-herbivore interactions.}, } @article {pmid30038771, year = {2018}, author = {Broekhuis, F}, title = {Natural and anthropogenic drivers of cub recruitment in a large carnivore.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6748-6755}, pmid = {30038771}, issn = {2045-7758}, abstract = {Recruitment is a critical parameter governing population dynamics and influences population persistence. Understanding the drivers of recruitment is therefore important for conservation, especially for long-lived mammals such as large carnivores, which have low reproductive rates, rendering them prone to extinction. Using cheetahs (Acinonyx jubatus) as a model species, I investigated the variation in cub recruitment in relation to habitat and the abundance of tourists and predators. Per litter, female cheetahs on average raised 1.71 ± 1.35 cubs to independence, but this varied depending on the presence of open habitat and the abundance of tourists, both of which had a negative effect on cub recruitment. More specifically, female cheetahs that were mostly found in open habitats on average raised 1.69 ± 0.14 cubs per litter to independence compared to 3.04 ± 0.26 cubs in denser habitat. Similarly, female cheetahs that were exposed to high tourist abundance on average raised 0.21 ± 0.72 cubs to independence compared to 2.32 ± 0.11 cubs in low tourism areas. Neither lion nor spotted hyaena abundance had an impact on the number of cubs that were recruited. Based on these findings, I recommend that the importance of a heterogeneous environment should be taken into consideration in habitat management, restoration efforts, and reintroduction programs. In addition, tourist quotas should be put in place in high visitation areas and strict wildlife viewing guidelines, such as number of vehicles, tourist behavior, time spent, and distance to a sighting, should be enforced. Cub recruitment is an important component of species persistence and incorporating these findings could aid conservation efforts for species that are increasingly under threat.}, } @article {pmid30038770, year = {2018}, author = {Miller, IF and Schneider-Crease, I and Nunn, CL and Muehlenbein, MP}, title = {Estimating infection prevalence: Best practices and their theoretical underpinnings.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6738-6747}, pmid = {30038770}, issn = {2045-7758}, abstract = {Accurately estimating infection prevalence is fundamental to the study of population health, disease dynamics, and infection risk factors. Prevalence is estimated as the proportion of infected individuals ("individual-based estimation"), but is also estimated as the proportion of samples in which evidence of infection is detected ("anonymous estimation"). The latter method is often used when researchers lack information on individual host identity, which can occur during noninvasive sampling of wild populations or when the individual that produced a fecal sample is unknown. The goal of this study was to investigate biases in individual-based versus anonymous prevalence estimation theoretically and to test whether mathematically derived predictions are evident in a comparative dataset of gastrointestinal helminth infections in nonhuman primates. Using a mathematical model, we predict that anonymous estimates of prevalence will be lower than individual-based estimates when (a) samples from infected individuals do not always contain evidence of infection and/or (b) when false negatives occur. The mathematical model further predicts that no difference in bias should exist between anonymous estimation and individual-based estimation when one sample is collected from each individual. Using data on helminth parasites of primates, we find that anonymous estimates of prevalence are significantly and substantially (12.17%) lower than individual-based estimates of prevalence. We also observed that individual-based estimates of prevalence from studies employing single sampling are on average 6.4% higher than anonymous estimates, suggesting a bias toward sampling infected individuals. We recommend that researchers use individual-based study designs with repeated sampling of individuals to obtain the most accurate estimate of infection prevalence. Moreover, to ensure accurate interpretation of their results and to allow for prevalence estimates to be compared among studies, it is essential that authors explicitly describe their sampling designs and prevalence calculations in publications.}, } @article {pmid30038769, year = {2018}, author = {Macintyre, PD and Van Niekerk, A and Dobrowolski, MP and Tsakalos, JL and Mucina, L}, title = {Impact of ecological redundancy on the performance of machine learning classifiers in vegetation mapping.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6728-6737}, pmid = {30038769}, issn = {2045-7758}, abstract = {Vegetation maps are models of the real vegetation patterns and are considered important tools in conservation and management planning. Maps created through traditional methods can be expensive and time-consuming, thus, new more efficient approaches are needed. The prediction of vegetation patterns using machine learning shows promise, but many factors may impact on its performance. One important factor is the nature of the vegetation-environment relationship assessed and ecological redundancy. We used two datasets with known ecological redundancy levels (strength of the vegetation-environment relationship) to evaluate the performance of four machine learning (ML) classifiers (classification trees, random forests, support vector machines, and nearest neighbor). These models used climatic and soil variables as environmental predictors with pretreatment of the datasets (principal component analysis and feature selection) and involved three spatial scales. We show that the ML classifiers produced more reliable results in regions where the vegetation-environment relationship is stronger as opposed to regions characterized by redundant vegetation patterns. The pretreatment of datasets and reduction in prediction scale had a substantial influence on the predictive performance of the classifiers. The use of ML classifiers to create potential vegetation maps shows promise as a more efficient way of vegetation modeling. The difference in performance between areas with poorly versus well-structured vegetation-environment relationships shows that some level of understanding of the ecology of the target region is required prior to their application. Even in areas with poorly structured vegetation-environment relationships, it is possible to improve classifier performance by either pretreating the dataset or reducing the spatial scale of the predictions.}, } @article {pmid30038768, year = {2018}, author = {Minden, V and Schnetger, B and Pufal, G and Leonhardt, SD}, title = {Antibiotic-induced effects on scaling relationships and on plant element contents in herbs and grasses.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6699-6713}, pmid = {30038768}, issn = {2045-7758}, abstract = {Plant performance is correlated with element concentrations in plant tissue, which may be impacted by adverse chemical soil conditions. Antibiotics of veterinary origin can adversely affect plant performance. They are released to agricultural fields via grazing animals or manure, taken up by plants and may be stored, transformed or sequestered by plant metabolic processes. We studied the potential effects of three antibiotics (penicillin, sulfadiazine, and tetracycline) on plant element contents (macro- and microelements). Plant species included two herb species (Brassica napus and Capsella bursa-pastoris) and two grass species (Triticum aestivum and Apera spica-venti), representing two crop species and two noncrop species commonly found in field margins, respectively. Antibiotic concentrations were chosen as to reflect in vivo situations, that is, relatively low concentrations similar to those detected in soils. In a greenhouse experiment, plants were raised in soil spiked with antibiotics. After harvest, macro- and microelements in plant leaves, stems, and roots were determined (mg/g). Results indicate that antibiotics can affect element contents in plants. Penicillin exerted the greatest effect both on element contents and on scaling relationships of elements between plant organs. Roots responded strongest to antibiotics compared to stems and leaves. We conclude that antibiotics in the soil, even in low concentrations, lead to low-element homeostasis, altering the scaling relationships between roots and other plant organs, which may affect metabolic processes and ultimately the performance of a plant.}, } @article {pmid30038767, year = {2018}, author = {Azpillaga, M and Real, J and Hernández-Matías, A}, title = {Effects of rearing conditions on natal dispersal processes in a long-lived predator bird.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6682-6698}, pmid = {30038767}, issn = {2045-7758}, abstract = {Natal or prebreeding dispersal is a key driver of the functioning, dynamics, and evolution of populations. Conditions experienced by individuals during development, that is, rearing conditions, may have serious consequences for the multiple components that shape natal dispersal processes. Rearing conditions vary as a result of differences in parental and environmental quality, and it has been shown that favorable rearing conditions are beneficial for individuals throughout their lives. However, the long-term consequences of rearing conditions on natal dispersal are still not fully understood in long-lived birds. In this study, we aim to test the following hypotheses to address the relationship between rearing conditions and certain components of the natal dispersal process in Bonelli's eagle (Aquila fasciata): (1) The body condition of nestlings depends on the quality of the territory and/or breeders; and (2) the survival until recruitment, (3) the age of recruitment, and (4) the natal dispersal distance (NDD) all depend on rearing conditions. As expected, nestlings reared in territories with high past productivity of chicks had better body condition, which indicates that both body condition and past productivity reflect the rearing conditions under which chicks are raised. In addition, chicks raised in territories with high past productivity and with good body condition had greater chances of surviving until recruitment. Furthermore, birds that have better condition recruit earlier, and males recruit at a younger age than females. At last, although females in good body condition exhibited higher NDD when they recruited at younger ages, this pattern was not observed in either older females or males. Overall, this study provides evidence that rearing conditions have important long-term consequences in long-lived birds. On the basis of our results, we advocate that conservation managers work actively in the promotion of actions aimed at improving the rearing conditions under which individuals develop in threatened populations.}, } @article {pmid30038766, year = {2018}, author = {Kozma, R and Lillie, M and Benito, BM and Svenning, JC and Höglund, J}, title = {Past and potential future population dynamics of three grouse species using ecological and whole genome coalescent modeling.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6671-6681}, pmid = {30038766}, issn = {2045-7758}, abstract = {Studying demographic history of species provides insight into how the past has shaped the current levels of overall biodiversity and genetic composition of species, but also how these species may react to future perturbations. Here we investigated the demographic history of the willow grouse (Lagopus lagopus), rock ptarmigan (Lagopus muta), and black grouse (Tetrao tetrix) through the Late Pleistocene using two complementary methods and whole genome data. Species distribution modeling (SDM) allowed us to estimate the total range size during the Last Interglacial (LIG) and Last Glacial Maximum (LGM) as well as to indicate potential population subdivisions. Pairwise Sequentially Markovian Coalescent (PSMC) allowed us to assess fluctuations in effective population size across the same period. Additionally, we used SDM to forecast the effect of future climate change on the three species over the next 50 years. We found that SDM predicts the largest range size for the cold-adapted willow grouse and rock ptarmigan during the LGM. PSMC captured intraspecific population dynamics within the last glacial period, such that the willow grouse and rock ptarmigan showed multiple bottlenecks signifying recolonization events following the termination of the LGM. We also see signals of population subdivision during the last glacial period in the black grouse, but more data are needed to strengthen this hypothesis. All three species are likely to experience range contractions under future warming, with the strongest effect on willow grouse and rock ptarmigan due to their limited potential for northward expansion. Overall, by combining these two modeling approaches, we have provided a multifaceted examination of the biogeography of these species and how they have responded to climate change in the past. These results help us understand how cold-adapted species may respond to future climate changes.}, } @article {pmid30038765, year = {2018}, author = {Fisher, AM and Cornell, SJ and Holwell, GI and Price, TAR}, title = {Sexual cannibalism and population viability.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6663-6670}, pmid = {30038765}, issn = {2045-7758}, abstract = {Some behaviours that typically increase fitness at the individual level may reduce population persistence, particularly in the face of environmental changes. Sexual cannibalism is an extreme mating behaviour which typically involves a male being devoured by the female immediately before, during or after copulation, and is widespread amongst predatory invertebrates. Although the individual-level effects of sexual cannibalism are reasonably well understood, very little is known about the population-level effects. We constructed both a mathematical model and an individual-based model to predict how sexual cannibalism might affect population growth rate and extinction risk. We found that in the absence of any cannibalism-derived fecundity benefit, sexual cannibalism is always detrimental to population growth rate and leads to a higher population extinction risk. Increasing the fecundity benefits of sexual cannibalism leads to a consistently higher population growth rate and likely a lower extinction risk. However, even if cannibalism-derived fecundity benefits are large, very high rates of sexual cannibalism (>70%) can still drive the population to negative growth and potential extinction. Pre-copulatory cannibalism was particularly damaging for population growth rates and was the main predictor of growth declining below the replacement rate. Surprisingly, post-copulatory cannibalism had a largely positive effect on population growth rate when fecundity benefits were present. This study is the first to formally estimate the population-level effects of sexual cannibalism. We highlight the detrimental effect sexual cannibalism may have on population viability if (1) cannibalism rates become high, and/or (2) cannibalism-derived fecundity benefits become low. Decreased food availability could plausibly both increase the frequency of cannibalism, and reduce the fecundity benefit of cannibalism, suggesting that sexual cannibalism may increase the risk of population collapse in the face of environmental change.}, } @article {pmid30038764, year = {2018}, author = {Lynch, ZR and Penley, MJ and Morran, LT}, title = {Turnover in local parasite populations temporarily favors host outcrossing over self-fertilization during experimental evolution.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6652-6662}, pmid = {30038764}, issn = {2045-7758}, abstract = {The ubiquity of outcrossing in plants and animals is difficult to explain given its costs relative to self-fertilization. Despite these costs, exposure to changing environmental conditions can temporarily favor outcrossing over selfing. Therefore, recurring episodes of environmental change are predicted to favor the maintenance of outcrossing. Studies of host-parasite coevolution have provided strong support for this hypothesis. However, it is unclear whether multiple exposures to novel parasite genotypes in the absence of coevolution are sufficient to favor outcrossing. Using the nematode Caenorhabditis elegans and the bacterial parasite Serratia marcescens, we studied host responses to parasite turnover. We passaged several replicates of a host population that was well-adapted to the S. marcescens strain Sm2170 with either Sm2170 or one of three novel S. marcescens strains, each derived from Sm2170, for 18 generations. We found that hosts exposed to novel parasites maintained higher outcrossing rates than hosts exposed to Sm2170. Nonetheless, host outcrossing rates declined over time against all but the most virulent novel parasite strain. Hosts exposed to the most virulent novel strain exhibited increased outcrossing rates for approximately 12 generations, but did not maintain elevated levels of outcrossing throughout the experiment. Thus, parasite turnover can transiently increase host outcrossing. These results suggest that recurring episodes of parasite turnover have the potential to favor the maintenance of host outcrossing. However, such maintenance may require frequent exposure to novel virulent parasites, rapid rates of parasite turnover, and substantial host gene flow.}, } @article {pmid30038763, year = {2018}, author = {Salas-Lizana, R and Oono, R}, title = {Double-digest RADseq loci using standard Illumina indexes improve deep and shallow phylogenetic resolution of Lophodermium, a widespread fungal endophyte of pine needles.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6638-6651}, pmid = {30038763}, issn = {2045-7758}, abstract = {The phylogenetic and population genetic structure of symbiotic microorganisms may correlate with important ecological traits that can be difficult to directly measure, such as host preferences or dispersal rates. This study develops and tests a low-cost double-digest restriction site-associated DNA sequencing (ddRADseq) protocol to reveal among- and within-species genetic structure for Lophodermium, a genus of fungal endophytes whose evolutionary analyses have been limited by the scarcity of informative markers. The protocol avoids expensive barcoded adapters and incorporates universal indexes for multiplexing. We tested for reproducibility and functionality by comparing shared loci from sample replicates and assessed the effects of numbers of ambiguous sites and clustering thresholds on coverage depths, number of shared loci among samples, and phylogenetic reconstruction. Errors between technical replicates were minimal. Relaxing the quality-filtering criteria increased the mean coverage depth per locus and the number of loci recovered within a sample, but had little effect on the number of shared loci across samples. Increasing clustering threshold decreased the mean coverage depth per cluster and increased the number of loci recovered within a sample but also decreased the number of shared loci across samples, especially among distantly related species. The combination of low similarity clustering (70%) and relaxed quality-filtering (allowing up to 30 ambiguous sites per read) performed the best in phylogenetic analyses at both recent and deep genetic divergences. Hence, this method generated sufficient number of shared homologous loci to investigate the evolutionary relationships among divergent fungal lineages with small haploid genomes. The greater genetic resolution also revealed new structure within species that correlated with ecological traits, providing valuable insights into their cryptic life histories.}, } @article {pmid30038762, year = {2018}, author = {Ehrlich, E and Gaedke, U}, title = {Not attackable or not crackable-How pre- and post-attack defenses with different competition costs affect prey coexistence and population dynamics.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6625-6637}, pmid = {30038762}, issn = {2045-7758}, abstract = {It is well-known that prey species often face trade-offs between defense against predation and competitiveness, enabling predator-mediated coexistence. However, we lack an understanding of how the large variety of different defense traits with different competition costs affects coexistence and population dynamics. Our study focusses on two general defense mechanisms, that is, pre-attack (e.g., camouflage) and post-attack defenses (e.g., weaponry) that act at different phases of the predator-prey interaction. We consider a food web model with one predator, two prey types and one resource. One prey type is undefended, while the other one is pre- or post-attack defended paying costs either by a higher half-saturation constant for resource uptake or a lower maximum growth rate. We show that post-attack defenses promote prey coexistence and stabilize the population dynamics more strongly than pre-attack defenses by interfering with the predator's functional response: Because the predator spends time handling "noncrackable" prey, the undefended prey is indirectly facilitated. A high half-saturation constant as defense costs promotes coexistence more and stabilizes the dynamics less than a low maximum growth rate. The former imposes high costs at low resource concentrations but allows for temporally high growth rates at predator-induced resource peaks preventing the extinction of the defended prey. We evaluate the effects of the different defense mechanisms and costs on coexistence under different enrichment levels in order to vary the importance of bottom-up and top-down control of the prey community.}, } @article {pmid30038761, year = {2018}, author = {Liu, L and Pei, C and Liu, S and Guo, X and Du, N and Guo, W}, title = {Genetic and epigenetic changes during the invasion of a cosmopolitan species (Phragmites australis).}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6615-6624}, pmid = {30038761}, issn = {2045-7758}, abstract = {While many introduced invasive species can increase genetic diversity through multiple introductions and/or hybridization to colonize successfully in new environments, others with low genetic diversity have to persist by alternative mechanisms such as epigenetic variation. Given that Phragmites australis is a cosmopolitan reed growing in a wide range of habitats and its invasion history, especially in North America, has been relatively well studied, it provides an ideal system for studying the role and relationship of genetic and epigenetic variation in biological invasions. We used amplified fragment length polymorphism (AFLP) and methylation-sensitive (MS) AFLP methods to evaluate genetic and epigenetic diversity and structure in groups of the common reed across its range in the world. Evidence from analysis of molecular variance (AMOVA) based on AFLP and MS-AFLP data supported the previous conclusion that the invasive introduced populations of P. australis in North America were from European and Mediterranean regions. In the Gulf Coast region, the introduced group harbored a high level of genetic variation relative to originating group from its native location, and it showed epigenetic diversity equal to that of the native group, if not higher, while the introduced group held lower genetic diversity than the native. In the Great Lakes region, the native group displayed very low genetic and epigenetic variation, and the introduced one showed slightly lower genetic and epigenetic diversity than the original one. Unexpectedly, AMOVA and principal component analysis did not demonstrate any epigenetic convergence between native and introduced groups before genetic convergence. Our results suggested that intertwined changes in genetic and epigenetic variation were involved in the invasion success in North America. Although our study did not provide strong evidence proving the importance of epigenetic variation prior to genetic, it implied the similar role of stable epigenetic diversity to genetic diversity in the adaptation of P. australis to local environment.}, } @article {pmid30038760, year = {2018}, author = {Cammen, KM and Schultz, TF and Don Bowen, W and Hammill, MO and Puryear, WB and Runstadler, J and Wenzel, FW and Wood, SA and Kinnison, M}, title = {Genomic signatures of population bottleneck and recovery in Northwest Atlantic pinnipeds.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6599-6614}, pmid = {30038760}, issn = {2045-7758}, support = {HHSN272201400008C/AI/NIAID NIH HHS/United States ; }, abstract = {Population increases over the past several decades provide natural settings in which to study the evolutionary processes that occur during bottleneck, growth, and spatial expansion. We used parallel natural experiments of historical decline and subsequent recovery in two sympatric pinniped species in the Northwest Atlantic, the gray seal (Halichoerus grypus atlantica) and harbor seal (Phoca vitulina vitulina), to study the impact of recent demographic change in genomic diversity. Using restriction site-associated DNA sequencing, we assessed genomic diversity at over 8,700 polymorphic gray seal loci and 3,700 polymorphic harbor seal loci in samples from multiple cohorts collected throughout recovery over the past half-century. Despite significant differences in the degree of genetic diversity assessed in the two species, we found signatures of historical bottlenecks in the contemporary genomes of both gray and harbor seals. We evaluated temporal trends in diversity across cohorts, as well as compared samples from sites at both the center and edge of a recent gray seal range expansion, but found no significant change in genomewide diversity following recovery. We did, however, find that the variance and degree of allele frequency change measured over the past several decades were significantly different from neutral expectations of drift under population growth. These two cases of well-described demographic history provide opportunities for critical evaluation of current approaches to simulating and understanding the genetic effects of historical demographic change in natural populations.}, } @article {pmid30038759, year = {2018}, author = {Sander, NL and Pérez-Zavala, F and Da Silva, CJ and Arruda, JC and Pulido, MT and Barelli, MAA and Rossi, AB and Viana, AP and Boechat, MSB and Bacon, CD and Cibrián-Jaramillo, A}, title = {Rivers shape population genetic structure in Mauritia flexuosa (Arecaceae).}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6589-6598}, pmid = {30038759}, issn = {2045-7758}, abstract = {The Mauritia flexuosa L.f. palm is known as the "tree of life" given its importance as fundamental food and construction resources for humans. The species is broadly distributed in wet habitats of Amazonia and dry habitats of the Amazon and Orinoco river basins and in the Cerrado savanna. We collected 179 individuals from eight different localities throughout these habitats and used microsatellites to characterize their population structure and patterns of gene flow. Overall, we found high genetic variation, except in one savanna locality. Gene flow between populations is largely congruent with river basins and the direction of water flow within and among them, suggesting their importance for seed dispersal. Further, rivers have had a higher frequency of human settlements than forested sites, contributing to population diversity and structure through increased human use and consumption of M. flexuosa along rivers. Gene flow patterns revealed that migrants are sourced primarily from within the same river basin, such as those from Madeira and Tapajós basins. Our work suggests that rivers and their inhabitants are a critical element of the landscape in Amazonia and have impacted the dispersal and subsequent distribution of tropical palm species, as shown by the patterns of genetic variation in M. flexuosa.}, } @article {pmid30038758, year = {2018}, author = {Nguyen-Phuc, H and Berres, ME}, title = {Genetic structure in Red Junglefowl (Gallus gallus) populations: Strong spatial patterns in the wild ancestors of domestic chickens in a core distribution range.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6575-6588}, pmid = {30038758}, issn = {2045-7758}, abstract = {Red Junglefowl (Gallus gallus) are among the few remaining ancestors of an extant domesticated livestock species, the domestic chicken, that still occur in the wild. Little is known about genetic diversity, population structure, and demography of wild Red Junglefowl in their natural habitats. Extinction threats from habitat loss or genetic alteration from domestic introgression exacerbate further the conservation status of this progenitor species. In a previous study, we reported extraordinary adaptive genetic variation in the MHC B-locus in wild Red Junglefowl and no evidence of allelic introgression between wild and domestic chickens was observed. In this study, we characterized spatial genetic variation and population structure in naturally occurring populations of Red Junglefowl in their core distribution range in South Central Vietnam. A sample of 212 Red Junglefowl was obtained from geographically and ecologically diverse habitats across an area of 250 × 350 km. We used amplified fragment-length polymorphism markers obtained from 431 loci to determine whether genetic diversity and population structure varies. We found that Red Junglefowl are widely distributed but form small and isolated populations. Strong spatial genetic patterns occur at both local and regional scales. At local scale, population stratification can be identified to approximately 5 km. At regional scale, we identified distinct populations of Red Junglefowl in the southern lowlands, northern highlands, and eastern coastal portions of the study area. Both local and long-distance genetic patterns observed in wild Red Junglefowl may reflect the species' ground-dwelling and territorial characteristics, including dispersal barriers imposed by the Annamite Mountain Range. Spatially explicit analyses with neutral genetic markers can be highly informative and here elevates the conservation profile of the wild ancestors of domesticated chickens.}, } @article {pmid30038757, year = {2018}, author = {Alves, FM and Sartori, ÂLB and Zucchi, MI and Azevedo-Tozzi, AMG and Tambarussi, EV and Alves-Pereira, A and de Souza, AP}, title = {Genetic structure of two Prosopis species in Chaco areas: A lack of allelic diversity diagnosis and insights into the allelic conservation of the affected species.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6558-6574}, pmid = {30038757}, issn = {2045-7758}, abstract = {The Gran Chaco is the largest continuous region of the South American dry forest, spanning Argentina, Paraguay, Bolivia, and Brazil. Prosopis rubriflora and Prosopis ruscifolia are typical tree species of chaquenian area forests, which have been subjected to continuous fragmentation caused by cattle raising. This study evaluated P. rubriflora and P. ruscifolia in areas with varying levels of disturbance. We investigated the contemporary genetic diversities of both species in areas with distinct anthropogenic disturbances. Even with a lower heterozygote frequency, disturbed areas can provide important storage for alleles, allowing the maintenance of diversity. The genetic diversity of P. rubriflora was surprisingly similar to that of P. ruscifolia (He = 0.59 and He = 0.60, respectively) even with very different distribution ranges of both species. However, P. ruscifolia exhibited a higher intrapopulation fixation index than P. rubriflora. P. rubriflora showed evidence of bottlenecking in 64% of the sampled areas, while P. ruscifolia showed such evidence in 36% of the sampled areas. Additionally, P. rubriflora had two distinct populations due to its disjunctive geographic distribution, whereas P. ruscifolia had a single population that exhibited few signs of population structure in some areas, possibly due to the main pollinators presenting a short range of dispersion. Our results suggest that 42 Chaco areas should be conserved to retain the minimum of 500 individuals necessary to maintain genetic diversity for 100-1,000 generations. This study improves our understanding of these two Prosopis species and provides information for the conservation of their genetic diversities.}, } @article {pmid30038756, year = {2018}, author = {Soulsbury, CD and Lipponen, A and Wood, K and Mein, CA and Hoffman, JI and Lebigre, C}, title = {Age- and quality-dependent DNA methylation correlate with melanin-based coloration in a wild bird.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6547-6557}, pmid = {30038756}, issn = {2045-7758}, abstract = {Secondary sexual trait expression can be influenced by fixed individual factors (such as genetic quality) as well as by dynamic factors (such as age and environmentally induced gene expression) that may be associated with variation in condition or quality. In particular, melanin-based traits are known to relate to condition and there is a well-characterized genetic pathway underpinning their expression. However, the mechanisms linking variable trait expression to genetic quality remain unclear. One plausible mechanism is that genetic quality could influence trait expression via differential methylation and differential gene expression. We therefore conducted a pilot study examining DNA methylation at a candidate gene (agouti-related neuropeptide: AgRP) in the black grouse Lyrurus tetrix. We specifically tested whether CpG methylation covaries with age and multilocus heterozygosity (a proxy of genetic quality) and from there whether the expression of a melanin-based ornament (ultraviolet-blue chroma) correlates with DNA methylation. Consistent with expectations, we found clear evidence for age- and heterozygosity-specific patterns of DNA methylation, with two CpG sites showing the greatest DNA methylation in highly heterozygous males at their peak age of reproduction. Furthermore, DNA methylation at three CpG sites was significantly positively correlated with ultraviolet-blue chroma. Ours is the first study to our knowledge to document age- and quality-dependent variation in DNA methylation and to show that dynamic sexual trait expression across the lifespan of an organism is associated with patterns of DNA methylation. Although we cannot demonstrate causality, our work provides empirical support for a mechanism that could potentially link key individual factors to variation in sexual trait expression in a wild vertebrate.}, } @article {pmid30038755, year = {2018}, author = {Lin, WT and Pennings, SC}, title = {Predator-prey interactions in a ladybeetle-aphid system depend on spatial scale.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6537-6546}, pmid = {30038755}, issn = {2045-7758}, abstract = {The outcome of species interactions may manifest differently at different spatial scales; therefore, our interpretation of observed interactions will depend on the scale at which observations are made. For example, in ladybeetle-aphid systems, the results from small-scale cage experiments usually cannot be extrapolated to landscape-scale field observations. To understand how ladybeetle-aphid interactions change across spatial scales, we evaluated predator-prey interactions in an experimental system. The experimental habitat consisted of 81 potted plants and was manipulated to facilitate analysis across four spatial scales. We also simulated a spatially explicit metacommunity model parallel to the experiment. In the experiment, we found that the negative effect of ladybeetles on aphids decreased with increasing spatial scales. This pattern can be explained by ladybeetles strongly suppressing aphids at small scales, but not colonizing distant patches fast enough to suppress aphids at larger scales. In the experiment, the positive effects of aphids on ladybeetles were strongest at three-plant scale. In a model scenario where predators did not have demographic dynamics, we found, consistent with the experiment, that both the effects of ladybeetles on aphids and the effects of aphids on ladybeetles decreased with increasing spatial scales. These patterns suggest that dispersal was the primary cause of ladybeetle population dynamics in our experiment: aphids increased ladybeetle numbers at smaller scales because ladybeetles stayed in a patch longer and performed area-restricted searches after encountering aphids; these behaviors did not affect ladybeetle numbers at larger spatial scales. The parallel experimental and model results illustrate how predator-prey interactions can change across spatial scales, suggesting that our interpretation of observed predator-prey dynamics would differ if observations were made at different scales. This study demonstrates how studying ecological interactions at a range of scales can help link the results of small-scale ecological experiments to landscape-scale ecological problems.}, } @article {pmid30038754, year = {2018}, author = {Zhang, H and Qi, W and Liu, K}, title = {Functional traits associated with plant colonizing and competitive ability influence species abundance during secondary succession: Evidence from subalpine meadows of the Qinghai-Tibetan Plateau.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6529-6536}, pmid = {30038754}, issn = {2045-7758}, abstract = {It is widely recognized that colonists and competitors dominate early and late succession, respectively, with selected species having different colonizing and competitive abilities. However, it remains unknown whether colonizing and competitive ability can determine species abundance directly over succession. The data for five key functional traits were collected (photosynthesis rate, leaf turgor loss point, leaf proline content, seed mass, and seed germination rate), which are direct indicators of plant competitive and colonizing abilities including growth, drought and cold stress resistance, dispersal, and seed dormancy. Here, we tested the effects of colonizing and competitive abilities on species abundance, by employing a linear mixed-effects model to examine the shifts in the relationship between species abundance and these five colonization and competition-related traits in species-rich subalpine secondary successional meadows (at 4, 6, 10, 13 years of age, and undisturbed, respectively) of the Qinghai-Tibetan Plateau. The abundant species at the early-successional meadows tend to have high photosynthetic rate, high leaf proline content, low seed mass, and seed germination rate for having high colonizing ability, but low competitive ability. By contrast, late-successional communities tend to be dominated by species with high competitive ability, but low colonizing ability, indicated by large seeds, high seed germination rate, low photosynthetic rate, and leaf proline content. The observed directional shifts in the relationships between traits (photosynthetic rate, leaf proline content, seed mass, and seed germination rate) and abundance with successional age, bring two new understandings of community assembly during succession of subalpine meadows in the Qinghai-Tibetan Plateau. First, it discloses that the differences in species abundance over succession can be directly attributed to differences in colonizing and competitive abilities of different species. Second, it expands the effects of multiple life historical differences including growth, resource competitive ability, cold stress resistance, dispersal, and seed germination strategy, represented by functional traits on community assembly along succession, that is, from the species to the community level.}, } @article {pmid30038753, year = {2018}, author = {Lozano-Jaramillo, M and McCracken, KG and Cadena, CD}, title = {Neutral and functionally important genes shed light on phylogeography and the history of high-altitude colonization in a widespread New World duck.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6515-6528}, pmid = {30038753}, issn = {2045-7758}, abstract = {Phylogeographic studies often infer historical demographic processes underlying species distributions based on patterns of neutral genetic variation, but spatial variation in functionally important genes can provide additional insights about biogeographic history allowing for inferences about the potential role of adaptation in geographic range evolution. Integrating data from neutral markers and genes involved in oxygen (O2)-transport physiology, we test historical hypotheses about colonization and gene flow across low- and high-altitude regions in the Ruddy Duck (Oxyura jamaicensis), a widely distributed species in the New World. Using multilocus analyses that for the first time include populations from the Colombian Andes, we also examined the hypothesis that Ruddy Duck populations from northern South America are of hybrid origin. We found that neutral and functional genes appear to have moved into the Colombian Andes from both North America and southern South America, and that high-altitude Colombian populations do not exhibit evidence of adaptation to hypoxia in hemoglobin genes. Therefore, the biogeographic history of Ruddy Ducks is likely more complex than previously inferred. Our new data raise questions about the hypothesis that adaptation via natural selection to high-altitude conditions through amino acid replacements in the hemoglobin protein allowed Ruddy Ducks to disperse south along the high Andes into southern South America. The existence of shared genetic variation with populations from both North America and southern South America as well as private alleles suggests that the Colombian population of Ruddy Ducks may be of old hybrid origin. This study illustrates the breadth of inferences one can make by combining data from nuclear and functionally important loci in phylogeography, and underscores the importance of complete range-wide sampling to study species history in complex landscapes.}, } @article {pmid30038752, year = {2018}, author = {Thambithurai, D and Hollins, J and Van Leeuwen, T and Rácz, A and Lindström, J and Parsons, K and Killen, SS}, title = {Shoal size as a key determinant of vulnerability to capture under a simulated fishery scenario.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6505-6514}, pmid = {30038752}, issn = {2045-7758}, abstract = {Group living is widespread among animals and has a range of positive effects on individual foraging and predator avoidance. For fishes, capture by humans constitutes a major source of mortality, and the ecological effects of group living could carry-over to harvest scenarios if fish are more likely to interact with fishing gears when in social groups. Furthermore, individual metabolic rate can affect both foraging requirements and social behaviors, and could, therefore, have an additional influence on which fish are most vulnerable to capture by fishing. Here, we studied whether social environment (i.e., social group size) and metabolic rate exert independent or interactive effects on the vulnerability of wild zebrafish (Danio rerio) to capture by a baited passive trap gear. Using video analysis, we observed the tendency for individual fish to enter a deployed trap when in different shoal sizes. Fish in larger groups were more vulnerable to capture than fish tested individually or at smaller group sizes. Specifically, focal fish in larger groups entered traps sooner, spent more total time within the trap, and were more likely to re-enter the trap after an escape. Contrary to expectations, there was evidence that fish with a higher SMR took longer to enter traps, possibly due to a reduced tendency to follow groupmates or attraction to conspecifics already within the trap. Overall, however, social influences appeared to largely overwhelm any link between vulnerability and metabolic rate. The results suggest that group behavior, which in a natural predation setting is beneficial for avoiding predators, could be maladaptive under a trap harvest scenario and be an important mediator of which traits are under harvest associated selection.}, } @article {pmid30038751, year = {2018}, author = {Cerda-Hurtado, IM and Mayek-Pérez, N and Hernández-Delgado, S and Muruaga-Martínez, JS and Reyes-Lara, MA and Reyes-Valdés, MH and González-Prieto, JM}, title = {Climatic adaptation and ecological descriptors of wild beans from Mexico.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6492-6504}, pmid = {30038751}, issn = {2045-7758}, abstract = {Despite its economic, social, biological, and cultural importance, wild forms of the genus Phaseolus are not well represented in germplasm banks, and they are at great risk due to changes in land use as well as climate change. To improve our understanding of the potential geographical distribution of wild beans (Phaseolus spp.) from Mexico and support in situ and ex situ conservation programs, we determined the climatic adaptation ranges of 29 species and two subspecies of Phaseolus collected throughout Mexico. Based on five biotic and 117 abiotic variables obtained from different databases-WorldClim, Global-Aridity, and Global-PET-we performed principal component and cluster analyses. Germplasm was distributed among 12 climatic types from a possible 28. The general climatic ranges were as follows: 8-3,083 m above sea level; 12.07-26.96°C annual mean temperature; 10.33-202.68 mm annual precipitation; 9.33-16.56 W/m2 of net radiation; 11.68-14.23 hr photoperiod; 0.06-1.57 aridity index; and 10-1,728 mm/month of annual potential evapotranspiration. Most descriptive variables (25) clustered species into two groups: One included germplasm from semihot climates, and the other included germplasm from temperate climates. Species clustering showed 45% to 54% coincidence with species previously grouped using molecular data. The species P. filiformis, P. purpusii, and P. maculatus were found at low-humidity locations; these species could be used to improve our understanding of the extreme aridity adaptation mechanisms used by wild beans to avoid or tolerate climate change as well as to introgress favorable alleles into new cultivars adapted to hot, dry environments.}, } @article {pmid30038750, year = {2018}, author = {Végvári, Z and Katona, G and Vági, B and Freckleton, RP and Gaillard, JM and Székely, T and Liker, A}, title = {Sex-biased breeding dispersal is predicted by social environment in birds.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6483-6491}, pmid = {30038750}, issn = {2045-7758}, abstract = {Sex-biased dispersal is common in vertebrates, although the ecological and evolutionary causes of sex differences in dispersal are debated. Here, we investigate sex differences in both natal and breeding dispersal distances using a large dataset on birds including 86 species from 41 families. Using phylogenetic comparative analyses, we investigate whether sex-biased natal and breeding dispersal are associated with sexual selection, parental sex roles, adult sex ratio (ASR), or adult mortality. We show that neither the intensity of sexual selection, nor the extent of sex bias in parental care was associated with sex-biased natal or breeding dispersal. However, breeding dispersal was related to the social environment since male-biased ASRs were associated with female-biased breeding dispersal. Male-biased ASRs were associated with female-biased breeding dispersal. Sex bias in adult mortality was not consistently related to sex-biased breeding dispersal. These results may indicate that the rare sex has a stronger tendency to disperse in order to find new mating opportunities. Alternatively, higher mortality of the more dispersive sex could account for biased ASRs, although our results do not give a strong support to this explanation. Whichever is the case, our findings improve our understanding of the causes and consequences of sex-biased dispersal. Since the direction of causality is not yet known, we call for future studies to identify the causal relationships linking mortality, dispersal, and ASR.}, } @article {pmid30038749, year = {2018}, author = {Sheriff, MJ and Dantzer, B and Love, OP and Orrock, JL}, title = {Error management theory and the adaptive significance of transgenerational maternal-stress effects on offspring phenotype.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6473-6482}, pmid = {30038749}, issn = {2045-7758}, abstract = {It is well established that circulating maternal stress hormones (glucocorticoids, GCs) can alter offspring phenotype. There is also a growing body of empirical work, within ecology and evolution, indicating that maternal GCs link the environment experienced by the mother during gestation with changes in offspring phenotype. These changes are considered to be adaptive if the maternal environment matches the offspring's environment and maladaptive if it does not. While these ideas are conceptually sound, we lack a testable framework that can be used to investigate the fitness costs and benefits of altered offspring phenotypes across relevant future environments. We present error management theory as the foundation for a framework that can be used to assess the adaptive potential of maternal stress hormones on offspring phenotype across relevant postnatal scenarios. To encourage rigorous testing of our framework, we provide field-testable hypotheses regarding the potential adaptive role of maternal stress across a diverse array of taxa and life histories, as well as suggestions regarding how our framework might provide insight into past, present, and future research. This perspective provides an informed lens through which to design and interpret experiments on the effects of maternal stress, provides a framework for predicting and testing variation in maternal stress across and within taxa, and also highlights how rapid environmental change that induces maternal stress may lead to evolutionary traps.}, } @article {pmid30038748, year = {2018}, author = {Varudkar, A and Ramakrishnan, U}, title = {Gut microflora may facilitate adaptation to anthropic habitat: A comparative study in Rattus.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6463-6472}, pmid = {30038748}, issn = {2045-7758}, abstract = {Anthropophilic species ("commensal" species) that are completely dependent upon anthropic habitats experience different selective pressures particularly in terms of food than their noncommensal counterparts. Using a next-generation sequencing approach, we characterized and compared the gut microflora community of 53 commensal Rattus rattus and 59 noncommensal Rattus satarae captured in 10 locations in the Western Ghats, India. We observed that, while species identity was important in characterizing the microflora communities of the two Rattus hosts, environmental factors also had a significant effect. While there was significant geographic variation in the microflora of the noncommensal R. satarae, there was no effect of geographic distance on gut microflora of the commensal R. rattus. Interestingly, host genetic distance did not significantly influence the community in either Rattus hosts. Collectively, these results indicate that a shift in habitat is likely to result in a change in the gut microflora community and imply that the gut microflora is a complex trait, influenced by various parameters in different habitats.}, } @article {pmid30038747, year = {2018}, author = {Ludwig, L and Barbour, MA and Guevara, J and Avilés, L and González, AL}, title = {Caught in the web: Spider web architecture affects prey specialization and spider-prey stoichiometric relationships.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6449-6462}, pmid = {30038747}, issn = {2045-7758}, abstract = {Quantitative approaches to predator-prey interactions are central to understanding the structure of food webs and their dynamics. Different predatory strategies may influence the occurrence and strength of trophic interactions likely affecting the rates and magnitudes of energy and nutrient transfer between trophic levels and stoichiometry of predator-prey interactions. Here, we used spider-prey interactions as a model system to investigate whether different spider web architectures-orb, tangle, and sheet-tangle-affect the composition and diet breadth of spiders and whether these, in turn, influence stoichiometric relationships between spiders and their prey. Our results showed that web architecture partially affects the richness and composition of the prey captured by spiders. Tangle-web spiders were specialists, capturing a restricted subset of the prey community (primarily Diptera), whereas orb and sheet-tangle web spiders were generalists, capturing a broader range of prey types. We also observed elemental imbalances between spiders and their prey. In general, spiders had higher requirements for both nitrogen (N) and phosphorus (P) than those provided by their prey even after accounting for prey biomass. Larger P imbalances for tangle-web spiders than for orb and sheet-tangle web spiders suggest that trophic specialization may impose strong elemental constraints for these predators unless they display behavioral or physiological mechanisms to cope with nutrient limitation. Our findings suggest that integrating quantitative analysis of species interactions with elemental stoichiometry can help to better understand the occurrence of stoichiometric imbalances in predator-prey interactions.}, } @article {pmid30038746, year = {2018}, author = {Mensinger, AF and Putland, RL and Radford, CA}, title = {The effect of motorboat sound on Australian snapper Pagrus auratus inside and outside a marine reserve.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6438-6448}, pmid = {30038746}, issn = {2045-7758}, abstract = {Human-generated sound affects hearing, movement, and communication in both aquatic and terrestrial animals, but direct natural underwater behavioral observations are lacking. Baited underwater video (BUV) were deployed in near shore waters adjacent to Goat Island in the Cape Rodney-Okakari Point Marine Reserve (protected) or outside the reserve approximately four km south in Mathesons Bay (open), New Zealand to determine the natural behavior of Australian snapper Pagrus auratus exposed to motorboat sound. BUVs worked effectively at bringing fish into video range to assess the effects of sound. The snapper inhabiting the protected area showed no behavioral response to motorboat transits; however, fish in the open zones either scattered from the video frame or decreased feeding activity during boat presence. Our study suggests that motorboat sound, a common source of anthropogenic activity in the marine environment can affect fish behavior differently depending on the status of their habitat (protected versus open).}, } @article {pmid30038745, year = {2018}, author = {Lait, LA and Marshall, HD and Carr, SM}, title = {Phylogeographic mitogenomics of Atlantic cod Gadus morhua: Variation in and among trans-Atlantic, trans-Laurentian, Northern cod, and landlocked fjord populations.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6420-6437}, pmid = {30038745}, issn = {2045-7758}, abstract = {The historical phylogeography, biogeography, and ecology of Atlantic cod (Gadus morhua) have been impacted by cyclic Pleistocene glaciations, where drops in sea temperatures led to sequestering of water in ice sheets, emergence of continental shelves, and changes to ocean currents. High-resolution, whole-genome mitogenomic phylogeography can help to elucidate this history. We identified eight major haplogroups among 153 fish from 14 populations by Bayesian, parsimony, and distance methods, including one that extends the species coalescent back to ca. 330 kya. Fish from the Barents and Baltic Seas tend to occur in basal haplogroups versus more recent distribution of fish in the Northwest Atlantic. There was significant differentiation in the majority of trans-Atlantic comparisons (ΦST = .029-.180), but little or none in pairwise comparisons within the Northwest Atlantic of individual populations (ΦST = .000-.060) or defined management stocks (ΦST = .000-.023). Monte Carlo randomization tests of population phylogeography showed significantly nonrandom trans-Atlantic phylogeography versus absence of such structure within various partitions of trans-Laurentian, Northern cod (NAFO 2J3KL) and other management stocks, and Flemish Cap populations. A landlocked meromictic fjord on Baffin Island comprised multiple identical or near-identical mitogenomes in two major polyphyletic clades, and was significantly differentiated from all other populations (ΦST = .153-.340). The phylogeography supports a hypothesis of an eastern origin of genetic diversity ca. 200-250 kya, rapid expansion of a western superhaplogroup comprising four haplogroups ca. 150 kya, and recent postglacial founder populations.}, } @article {pmid30038744, year = {2018}, author = {Balan, RK and Ramasamy, A and Hande, RH and Gawande, SJ and Krishna Kumar, NK}, title = {Genome-wide identification, expression profiling, and target gene analysis of microRNAs in the Onion thrips, Thrips tabaci Lindeman (Thysanoptera: Thripidae), vectors of tospoviruses (Bunyaviridae).}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6399-6419}, pmid = {30038744}, issn = {2045-7758}, abstract = {Thrips tabaci Lindeman is an important polyphagous insect pest species estimated to cause losses of more than U.S. $1 billion worldwide annually. Chemical insecticides are of limited use in the management of T. tabaci due to the thigmokinetic behavior and development of resistance to insecticides. There is an urgent need to find alternative management strategies. Small noncoding RNAs (sncRNAs) especially microRNAs (miRNAs) hold great promise as key regulators of gene expression in a wide range of organisms. MiRNAs are a group of endogenously originated sncRNA known to regulate gene expression in animals, plants, and protozoans. In this study, we explored these RNAs in T. tabaci using deep sequencing to provide a basis for future studies of their biological and physiological roles in governing gene expression. Apart from snoRNAs and piRNAs, our study identified nine novel and 130 known miRNAs from T. tabaci. Functional classification of the targets for these miRNAs predicted that majority are involved in regulating transcription, translation, signal transduction and genetic information processing. The higher expression of few miRNAs (such as tta-miR-281, tta-miR-184, tta-miR-3533, tta-miR-N1, tta-miR-N7, and tta-miR-N9) in T. tabaci pupal and adult stages reflected their possible role in larval and adult development, metamorphosis, parthenogenesis, and reproduction. This is the first exploration of the miRNAome in T. tabaci, which not only provides insights into their possible role in insect metamorphosis, growth, and development but also offer an important resource for future pest management strategies.}, } @article {pmid30038743, year = {2018}, author = {Grégoir, AF and Thoré, ESJ and Philippe, C and Pinceel, T and Brendonck, L and Vanschoenwinkel, B}, title = {Squeezing out the last egg-annual fish increase reproductive efforts in response to a predation threat.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6390-6398}, pmid = {30038743}, issn = {2045-7758}, abstract = {Both constitutive and inducible antipredator strategies are ubiquitous in nature and serve to maximize fitness under a predation threat. Inducible strategies may be favored over constitutive defenses depending on their relative cost and benefit and temporal variability in predator presence. In African temporary ponds, annual killifish of the genus Nothobranchius are variably exposed to predators, depending on whether larger fish invade their habitat from nearby rivers during floods. Nonetheless, potential plastic responses to predation risk are poorly known. Here, we studied whether Nothobranchius furzeri individuals adjust their life history in response to a predation threat. For this, we monitored key life history traits in response to cues that signal the presence of predatory pumpkinseed sunfish (Lepomis gibbosus). While growth rate, adult body size, age at maturation, and initial fecundity were not affected, peak and total fecundity were higher in the predation risk treatment. This contrasts with known life history strategies of killifish from permanent waters, which tend to reduce reproduction in the presence of predators. Although our results show that N. furzeri individuals are able to detect predators and respond to their presence by modulating their reproductive output, these responses only become evident after a few clutches have been deposited. Overall our findings suggest that, in the presence of a predation risk, it can be beneficial to increase the production of life stages that can persist until the predation risk has faded.}, } @article {pmid30038742, year = {2018}, author = {Olsson, M and Loeb, L and Lindsay, W and Wapstra, E and Fitzpatrick, L and Shine, R}, title = {Extreme plasticity in reproductive biology of an oviparous lizard.}, journal = {Ecology and evolution}, volume = {8}, number = {13}, pages = {6384-6389}, pmid = {30038742}, issn = {2045-7758}, abstract = {Most oviparous squamate reptiles lay their eggs when embryos have completed less than one-third of development, with the remaining two-thirds spent in an external nest. Even when females facultatively retain eggs in dry or cold conditions, such retention generally causes only a minor (<10%) decrease in subsequent incubation periods. In contrast, we found that female sand lizards (Lacerta agilis) from an experimentally founded field population (established ca. 20 years ago on the southwest coast of Sweden) exhibited wide variation in incubation periods even when the eggs were kept at standard (25°C) conditions. Females that retained eggs in utero for longer based on the delay between capture and oviposition produced eggs that hatched sooner. In the extreme case, eggs hatched after only 55% of the "normal" incubation period. Although the proximate mechanisms underlying this flexibility remain unclear, our results from this first full field season at the new study site show that females within a single cold-climate population of lizards can span a substantial proportion of the continuum from "normal" oviparity to viviparity.}, } @article {pmid30038485, year = {2018}, author = {Karimi, K and Wuitchik, DM and Oldach, MJ and Vize, PD}, title = {Distinguishing Species Using GC Contents in Mixed DNA or RNA Sequences.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318788866}, pmid = {30038485}, issn = {1176-9343}, support = {P41 HD064556/HD/NICHD NIH HHS/United States ; }, abstract = {With the advent of whole transcriptome and genome analysis methods, classifying samples containing multiple origins has become a significant task. Nucleotide sequences can be allocated to a genome or transcriptome by aligning sequences to multiple target sequence sets, but this approach requires extensive computational resources and also depends on target sequence sets lacking contaminants, which is often not the case. Here, we demonstrate that raw sequences can be rapidly sorted into groups, in practice corresponding to genera, by exploiting differences in nucleotide GC content. To do so, we introduce GCSpeciesSorter, which uses classification, specifically Support Vector Machines (SVM) and the C4.5 decision tree generator, to differentiate sequences. It also implements a secondary BLAST feature to identify known outliers. In the test case presented, a hermatypic coral holobiont, the cnidarian host includes various endosymbionts. The best characterized and most common of these symbionts are zooxanthellae of the genus Symbiodinium. GCSpeciesSorter separates cnidarian from Symbiodinium sequences with a high degree of accuracy. We show that if the GC contents of the species differ enough, this method can be used to accurately distinguish the sequences of different species when using high-throughput sequencing technologies.}, } @article {pmid30038484, year = {2018}, author = {Watanabe, T and Yamazaki, S and Maita, C and Matushita, M and Matsuo, J and Okubo, T and Yamaguchi, H}, title = {Lateral Gene Transfer Between Protozoa-Related Giant Viruses of Family Mimiviridae and Chlamydiae.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318788337}, pmid = {30038484}, issn = {1176-9343}, abstract = {Obligate intracellular chlamydiae diverged into pathogenic and environmental chlamydiae 0.7-1.4 billion years ago. While pathogenic chlamydiae have adapted to a wide range of vertebrates, environmental chlamydiae inhabit unicellular amoebae, the free-living Acanthamoeba. However, how and why this divergence occurred remains unclear. Meanwhile, giant viruses consisting of protozoa-related and protozoa-unrelated viruses have been discovered, with the former group being suggested to have more influenced environmental chlamydiae during their evolution while cohabiting host amoebae. Against this background, we attempted to visualize genes of giant viruses in chlamydial genomes by bioinformatic analysis mainly with comparative genome and phylogenic analysis, seeking genes present in chlamydiae that are specifically shared with protozoa-related giant viruses. As a result, in contrast to protozoa-unrelated giant viruses, the genes of protozoa-related giant viruses were significantly shared in both the chlamydia genomes depending on the giant virus type. In particular, the prevalence of Mimiviridae genes among the protozoa-related giant virus genes in chlamydial genomes was significantly high. Meanwhile, the prevalence of protozoa-related giant virus genes in pathogenic chlamydia genomes was consistently higher than those of environmental chlamydiae; the actual number of sequences similar to giant virus was also significantly predominant compared with those in the environmental chlamydial genomes. Among them, the most prevalent of giant virus was in the case of chlamydiae with Megavirus chiliensis; total of 1338 genes of the chlamydiae were found to be shared with the virus (444 genes specific to environmental chlamydiae, 892 genes shared between both chlamydiae, only two genes in the pathogenic chlamydiae). Phylogenic analysis with most prevalent sets (Megavirus chiliensis and Protochlamydia EI2 or Chlamydia trachomatis L2 434Bu) showed the presence of orthologs between these with several clustered. In addition, Pearson's single regression analysis revealed that almost the prevalence of the genes from the giant viruses in chlamydial genomes was negatively and specifically correlated with the number of chlamydial open reading frames (ORFs). Thus, these results indicated the trace of lateral gene transfer between protozoa-related giant viruses of family Mimiviridae and chlamydiae. This is the first demonstration of a putative linkage between chlamydiae and the giant viruses, providing us with a hint to understand chlamydial evolution.}, } @article {pmid30038418, year = {2018}, author = {}, title = {Through a child's eyes.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1191}, doi = {10.1038/s41559-018-0645-9}, pmid = {30038418}, issn = {2397-334X}, } @article {pmid30038417, year = {2018}, author = {Tulloch, AIT and Auerbach, N and Avery-Gomm, S and Bayraktarov, E and Butt, N and Dickman, CR and Ehmke, G and Fisher, DO and Grantham, H and Holden, MH and Lavery, TH and Leseberg, NP and Nicholls, M and O'Connor, J and Roberson, L and Smyth, AK and Stone, Z and Tulloch, V and Turak, E and Wardle, GM and Watson, JEM}, title = {A decision tree for assessing the risks and benefits of publishing biodiversity data.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1209-1217}, doi = {10.1038/s41559-018-0608-1}, pmid = {30038417}, issn = {2397-334X}, abstract = {Inadequate information on the geographical distribution of biodiversity hampers decision-making for conservation. Major efforts are underway to fill knowledge gaps, but there are increasing concerns that publishing the locations of species is dangerous, particularly for species at risk of exploitation. While we recognize that well-informed control of location data for highly sensitive taxa is necessary to avoid risks, such as poaching or habitat disturbance by recreational visitors, we argue that ignoring the benefits of sharing biodiversity data could unnecessarily obstruct conservation efforts for species and locations with low risks of exploitation. We provide a decision tree protocol for scientists that systematically considers both the risks of exploitation and potential benefits of increased conservation activities. Our protocol helps scientists assess the impacts of publishing biodiversity data and aims to enhance conservation opportunities, promote community engagement and reduce duplication of survey efforts.}, } @article {pmid30038416, year = {2018}, author = {Dominy, NJ and Winters, S and Pease, DE and Higham, JP}, title = {Dr Seuss and the real Lorax.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1196-1198}, doi = {10.1038/s41559-018-0628-x}, pmid = {30038416}, issn = {2397-334X}, } @article {pmid30038397, year = {2018}, author = {Chen, H and Levo, M and Barinov, L and Fujioka, M and Jaynes, JB and Gregor, T}, title = {Dynamic interplay between enhancer-promoter topology and gene activity.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1296-1303}, pmid = {30038397}, issn = {1546-1718}, support = {R01 GM097275/GM/NIGMS NIH HHS/United States ; R01 GM117458/GM/NIGMS NIH HHS/United States ; U01 DA047730/DA/NIDA NIH HHS/United States ; U01 EB021239/EB/NIBIB NIH HHS/United States ; }, abstract = {A long-standing question in gene regulation is how remote enhancers communicate with their target promoters, and specifically how chromatin topology dynamically relates to gene activation. Here, we combine genome editing and multi-color live imaging to simultaneously visualize physical enhancer-promoter interaction and transcription at the single-cell level in Drosophila embryos. By examining transcriptional activation of a reporter by the endogenous even-skipped enhancers, which are located 150 kb away, we identify three distinct topological conformation states and measure their transition kinetics. We show that sustained proximity of the enhancer to its target is required for activation. Transcription in turn affects the three-dimensional topology as it enhances the temporal stability of the proximal conformation and is associated with further spatial compaction. Furthermore, the facilitated long-range activation results in transcriptional competition at the locus, causing corresponding developmental defects. Our approach offers quantitative insight into the spatial and temporal determinants of long-range gene regulation and their implications for cellular fates.}, } @article {pmid30038396, year = {2018}, author = {Lee, JJ and Wedow, R and Okbay, A and Kong, E and Maghzian, O and Zacher, M and Nguyen-Viet, TA and Bowers, P and Sidorenko, J and Karlsson Linnér, R and Fontana, MA and Kundu, T and Lee, C and Li, H and Li, R and Royer, R and Timshel, PN and Walters, RK and Willoughby, EA and Yengo, L and , and , and , and Alver, M and Bao, Y and Clark, DW and Day, FR and Furlotte, NA and Joshi, PK and Kemper, KE and Kleinman, A and Langenberg, C and Mägi, R and Trampush, JW and Verma, SS and Wu, Y and Lam, M and Zhao, JH and Zheng, Z and Boardman, JD and Campbell, H and Freese, J and Harris, KM and Hayward, C and Herd, P and Kumari, M and Lencz, T and Luan, J and Malhotra, AK and Metspalu, A and Milani, L and Ong, KK and Perry, JRB and Porteous, DJ and Ritchie, MD and Smart, MC and Smith, BH and Tung, JY and Wareham, NJ and Wilson, JF and Beauchamp, JP and Conley, DC and Esko, T and Lehrer, SF and Magnusson, PKE and Oskarsson, S and Pers, TH and Robinson, MR and Thom, K and Watson, C and Chabris, CF and Meyer, MN and Laibson, DI and Yang, J and Johannesson, M and Koellinger, PD and Turley, P and Visscher, PM and Benjamin, DJ and Cesarini, D}, title = {Gene discovery and polygenic prediction from a genome-wide association study of educational attainment in 1.1 million individuals.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1112-1121}, doi = {10.1038/s41588-018-0147-3}, pmid = {30038396}, issn = {1546-1718}, support = {647648//European Research Council/International ; MC_UU_12015/2//Medical Research Council/United Kingdom ; R01 AG042568/AG/NIA NIH HHS/United States ; }, abstract = {Here we conducted a large-scale genetic association analysis of educational attainment in a sample of approximately 1.1 million individuals and identify 1,271 independent genome-wide-significant SNPs. For the SNPs taken together, we found evidence of heterogeneous effects across environments. The SNPs implicate genes involved in brain-development processes and neuron-to-neuron communication. In a separate analysis of the X chromosome, we identify 10 independent genome-wide-significant SNPs and estimate a SNP heritability of around 0.3% in both men and women, consistent with partial dosage compensation. A joint (multi-phenotype) analysis of educational attainment and three related cognitive phenotypes generates polygenic scores that explain 11-13% of the variance in educational attainment and 7-10% of the variance in cognitive performance. This prediction accuracy substantially increases the utility of polygenic scores as tools in research.}, } @article {pmid30038395, year = {2018}, author = {Sundaram, L and Gao, H and Padigepati, SR and McRae, JF and Li, Y and Kosmicki, JA and Fritzilas, N and Hakenberg, J and Dutta, A and Shon, J and Xu, J and Batzoglou, S and Li, X and Farh, KK}, title = {Predicting the clinical impact of human mutation with deep neural networks.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1161-1170}, pmid = {30038395}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; R01 GM089753/GM/NIGMS NIH HHS/United States ; R01 GM110240/GM/NIGMS NIH HHS/United States ; }, abstract = {Millions of human genomes and exomes have been sequenced, but their clinical applications remain limited due to the difficulty of distinguishing disease-causing mutations from benign genetic variation. Here we demonstrate that common missense variants in other primate species are largely clinically benign in human, enabling pathogenic mutations to be systematically identified by the process of elimination. Using hundreds of thousands of common variants from population sequencing of six non-human primate species, we train a deep neural network that identifies pathogenic mutations in rare disease patients with 88% accuracy and enables the discovery of 14 new candidate genes in intellectual disability at genome-wide significance. Cataloging common variation from additional primate species would improve interpretation for millions of variants of uncertain significance, further advancing the clinical utility of human genome sequencing.}, } @article {pmid30038344, year = {2018}, author = {Bernheim, A and Sorek, R}, title = {Viruses cooperate to defeat bacteria.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {482-484}, doi = {10.1038/d41586-018-05762-1}, pmid = {30038344}, issn = {1476-4687}, } @article {pmid30038342, year = {2018}, author = {Armstrong, A and Chou, IH and Mossinger, J and Thomas, C and Tobin Kårlström, C and White, M}, title = {Tropics.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {489}, doi = {10.1038/d41586-018-05770-1}, pmid = {30038342}, issn = {1476-4687}, mesh = {Animals ; *Biodiversity ; Carbon Cycle ; Dengue/epidemiology ; El Nino-Southern Oscillation ; Forests ; *Global Health ; Heart Diseases/mortality ; Humans ; Malaria/drug therapy/epidemiology/transmission ; Neoplasms/mortality ; Social Change ; *Sustainable Development ; *Tropical Climate ; Tuberculosis/drug therapy ; }, } @article {pmid30038311, year = {2018}, author = {Shen, Y and Zhou, H and Xu, J and Wang, Y and Zhang, Q and Walsh, TR and Shao, B and Wu, C and Hu, Y and Yang, L and Shen, Z and Wu, Z and Sun, Q and Ou, Y and Wang, Y and Wang, S and Wu, Y and Cai, C and Li, J and Shen, J and Zhang, R and Wang, Y}, title = {Anthropogenic and environmental factors associated with high incidence of mcr-1 carriage in humans across China.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1054-1062}, pmid = {30038311}, issn = {2058-5276}, support = {MR/P007295/1//Medical Research Council/United Kingdom ; }, abstract = {MCR-1-positve Escherichia coli (MCRPEC) have been reported in humans worldwide; however, thus far, their prevalence is low and potential sources for human mcr-1 carriage have not yet been identified. Here, we analyse a nationwide epidemiological dataset on MCRPEC in humans throughout China and assess the factors associated with MCRPEC carriage using natural and national anthropogenic data. We identified 774 non-duplicate MCRPEC isolates from 774 stool samples collected from 5,159 healthy individuals in 30 provinces and municipalities in 2016, with a prevalence of MCRPEC ranging from 3.7 to 32.7% (average: 15.0%)-substantially higher than previously reported. MCRPEC carriage was associated with provincial regions, the production of sheep and freshwater aquaculture, annual consumption of total meat, pork and mutton, and daily intake of aquaculture products. MCRPEC was significantly more prevalent in provinces with higher aquaculture industries. Whole-genome sequencing analysis revealed that the MCRPEC isolates were clustered into four distinct lineages, two of which were dominant and harboured most of the MCRPEC isolates. The high prevalence of MCRPEC in the community poses a substantial risk for colistin usage in clinical practice and suggests the need for intestinal screening of mcr-1 carriers in intensive care units in Chinese hospitals. Furthermore, our data suggest that aquaculture is a significant reservoir of mcr-1.}, } @article {pmid30038310, year = {2018}, author = {Duerkop, BA and Kleiner, M and Paez-Espino, D and Zhu, W and Bushnell, B and Hassell, B and Winter, SE and Kyrpides, NC and Hooper, LV}, title = {Murine colitis reveals a disease-associated bacteriophage community.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1023-1031}, pmid = {30038310}, issn = {2058-5276}, support = {K01 DK102436/DK/NIDDK NIH HHS/United States ; R01 DK070855/DK/NIDDK NIH HHS/United States ; }, abstract = {The dysregulation of intestinal microbial communities is associated with inflammatory bowel diseases (IBD). Studies aimed at understanding the contribution of the microbiota to inflammatory diseases have primarily focused on bacteria, yet the intestine harbours a viral component dominated by prokaryotic viruses known as bacteriophages (phages). Phage numbers are elevated at the intestinal mucosal surface and phages increase in abundance during IBD, suggesting that phages play an unidentified role in IBD. We used a sequence-independent approach for the selection of viral contigs and then applied quantitative metagenomics to study intestinal phages in a mouse model of colitis. We discovered that during colitis the intestinal phage population is altered and transitions from an ordered state to a stochastic dysbiosis. We identified phages specific to pathobiotic hosts associated with intestinal disease, whose abundances are altered during colitis. Additionally, phage populations in healthy and diseased mice overlapped with phages from healthy humans and humans with IBD. Our findings indicate that intestinal phage communities are altered during inflammatory disease, establishing a platform for investigating phage involvement in IBD.}, } @article {pmid30038309, year = {2018}, author = {Helfrich, EJN and Vogel, CM and Ueoka, R and Schäfer, M and Ryffel, F and Müller, DB and Probst, S and Kreuzer, M and Piel, J and Vorholt, JA}, title = {Bipartite interactions, antibiotic production and biosynthetic potential of the Arabidopsis leaf microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {909-919}, doi = {10.1038/s41564-018-0200-0}, pmid = {30038309}, issn = {2058-5276}, abstract = {Plants are colonized by phylogenetically diverse microorganisms that affect plant growth and health. Representative genome-sequenced culture collections of bacterial isolates from model plants, including Arabidopsis thaliana, have recently been established. These resources provide opportunities for systematic interaction screens combined with genome mining to discover uncharacterized natural products. Here, we report on the biosynthetic potential of 224 strains isolated from the A. thaliana phyllosphere. Genome mining identified more than 1,000 predicted natural product biosynthetic gene clusters (BGCs), hundreds of which are unknown compared to the MIBiG database of characterized BGCs. For functional validation, we used a high-throughput screening approach to monitor over 50,000 binary strain combinations. We observed 725 inhibitory interactions, with 26 strains contributing to the majority of these. A combination of imaging mass spectrometry and bioactivity-guided fractionation of the most potent inhibitor, the BGC-rich Brevibacillus sp. Leaf182, revealed three distinct natural product scaffolds that contribute to the observed antibiotic activity. Moreover, a genome mining-based strategy led to the isolation of a trans-acyltransferase polyketide synthase-derived antibiotic, macrobrevin, which displays an unprecedented natural product structure. Our findings demonstrate that the phyllosphere is a valuable environment for the identification of antibiotics and natural products with unusual scaffolds.}, } @article {pmid30038308, year = {2018}, author = {Munk, P and Knudsen, BE and Lukjancenko, O and Duarte, ASR and Van Gompel, L and Luiken, REC and Smit, LAM and Schmitt, H and Garcia, AD and Hansen, RB and Petersen, TN and Bossers, A and Ruppé, E and , and Lund, O and Hald, T and Pamp, SJ and Vigre, H and Heederik, D and Wagenaar, JA and Mevius, D and Aarestrup, FM}, title = {Abundance and diversity of the faecal resistome in slaughter pigs and broilers in nine European countries.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {898-908}, doi = {10.1038/s41564-018-0192-9}, pmid = {30038308}, issn = {2058-5276}, abstract = {Antimicrobial resistance (AMR) in bacteria and associated human morbidity and mortality is increasing. The use of antimicrobials in livestock selects for AMR that can subsequently be transferred to humans. This flow of AMR between reservoirs demands surveillance in livestock and in humans. We quantified and characterized the acquired resistance gene pools (resistomes) of 181 pig and 178 poultry farms from nine European countries, sequencing more than 5,000 Gb of DNA using shotgun metagenomics. We quantified acquired AMR using the ResFinder database and a second database constructed for this study, consisting of AMR genes identified through screening environmental DNA. The pig and poultry resistomes were very different in abundance and composition. There was a significant country effect on the resistomes, more so in pigs than in poultry. We found higher AMR loads in pigs, whereas poultry resistomes were more diverse. We detected several recently described, critical AMR genes, including mcr-1 and optrA, the abundance of which differed both between host species and between countries. We found that the total acquired AMR level was associated with the overall country-specific antimicrobial usage in livestock and that countries with comparable usage patterns had similar resistomes. However, functionally determined AMR genes were not associated with total drug use.}, } @article {pmid30038307, year = {2018}, author = {Trunk, K and Peltier, J and Liu, YC and Dill, BD and Walker, L and Gow, NAR and Stark, MJR and Quinn, J and Strahl, H and Trost, M and Coulthurst, SJ}, title = {The type VI secretion system deploys antifungal effectors against microbial competitors.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {920-931}, pmid = {30038307}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Interactions between bacterial and fungal cells shape many polymicrobial communities. Bacteria elaborate diverse strategies to interact and compete with other organisms, including the deployment of protein secretion systems. The type VI secretion system (T6SS) delivers toxic effector proteins into host eukaryotic cells and competitor bacterial cells, but, surprisingly, T6SS-delivered effectors targeting fungal cells have not been reported. Here we show that the 'antibacterial' T6SS of Serratia marcescens can act against fungal cells, including pathogenic Candida species, and identify the previously undescribed effector proteins responsible. These antifungal effectors, Tfe1 and Tfe2, have distinct impacts on the target cell, but both can ultimately cause fungal cell death. 'In competition' proteomics analysis revealed that T6SS-mediated delivery of Tfe2 disrupts nutrient uptake and amino acid metabolism in fungal cells, and leads to the induction of autophagy. Intoxication by Tfe1, in contrast, causes a loss of plasma membrane potential. Our findings extend the repertoire of the T6SS and suggest that antifungal T6SSs represent widespread and important determinants of the outcome of bacterial-fungal interactions.}, } @article {pmid30038306, year = {2018}, author = {Li, SH and Li, Z and Park, JO and King, CG and Rabinowitz, JD and Wingreen, NS and Gitai, Z}, title = {Escherichia coli translation strategies differ across carbon, nitrogen and phosphorus limitation conditions.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {939-947}, pmid = {30038306}, issn = {2058-5276}, support = {DP1 AI124669/AI/NIAID NIH HHS/United States ; R01 GM082938/GM/NIGMS NIH HHS/United States ; R01 GM107384/GM/NIGMS NIH HHS/United States ; }, abstract = {For cells to grow faster they must increase their protein production rate. Microorganisms have traditionally been thought to accomplish this increase by producing more ribosomes to enhance protein synthesis capacity, leading to the linear relationship between ribosome level and growth rate observed under most growth conditions previously examined. Past studies have suggested that this linear relationship represents an optimal resource allocation strategy for each growth rate, independent of any specific nutrient state. Here we investigate protein production strategies in continuous cultures limited for carbon, nitrogen and phosphorus, which differentially impact substrate supply for protein versus nucleic acid metabolism. Unexpectedly, we find that at slow growth rates, Escherichia coli achieves the same protein production rate using three different strategies under the three different nutrient limitations. Under phosphorus (P) limitation, translation is slow due to a particularly low abundance of ribosomes, which are RNA-rich and thus particularly costly for phosphorous-limited cells. Under nitrogen (N) limitation, translation elongation is slowed by processes including ribosome stalling at glutamine codons. Under carbon (C) limitation, translation is slowed by accumulation of inactive ribosomes not bound to messenger RNA. These extra ribosomes enable rapid growth acceleration during nutrient upshift. Thus, bacteria tune ribosome usage across different limiting nutrients to enable balanced nutrient-limited growth while also preparing for future nutrient upshifts.}, } @article {pmid30038286, year = {2018}, author = {Fei, Z and Zhao, W and Palomaki, TA and Sun, B and Miller, MK and Zhao, Z and Yan, J and Xu, X and Cobden, DH}, title = {Ferroelectric switching of a two-dimensional metal.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {336-339}, doi = {10.1038/s41586-018-0336-3}, pmid = {30038286}, issn = {1476-4687}, support = {DE-SC0002197//US Department of Energy/International ; DE-SC0018171//US Department of Energy/International ; DMR-1420451//National Science Foundation/International ; DMR-1420451//National Science Foundation/International ; 1433496//National Science Foundation/International ; 1719797//National Science Foundation/International ; }, abstract = {A ferroelectric is a material with a polar structure whose polarity can be reversed (switched) by applying an electric field1,2. In metals, itinerant electrons screen electrostatic forces between ions, which explains in part why polar metals are very rare3-7. Screening also excludes external electric fields, apparently ruling out the possibility of ferroelectric switching. However, in principle, a thin enough polar metal could be sufficiently penetrated by an electric field to have its polarity switched. Here we show that the topological semimetal WTe2 provides an embodiment of this principle. Although monolayer WTe2 is centro-symmetric and thus non-polar, the stacked bulk structure is polar. We find that two- or three-layer WTe2 exhibits spontaneous out-of-plane electric polarization that can be switched using gate electrodes. We directly detect and quantify the polarization using graphene as an electric-field sensor8. Moreover, the polarization states can be differentiated by conductivity and the carrier density can be varied to modify the properties. The temperature at which polarization vanishes is above 350 kelvin, and even when WTe2 is sandwiched between graphene layers it retains its switching capability at room temperature, demonstrating a robustness suitable for applications in combination with other two-dimensional materials9-12.}, } @article {pmid30038247, year = {2018}, author = {Cabral, RB and Gaines, SD and Mayorga, J and Clemence, M and Lynham, J and Koeshendrajana, S and Muawanah, U and Nugroho, D and Anna, Z and Mira, and Ghofar, A and Zulbainarni, N and Costello, C}, title = {Reply to 'Achieving sustainable and equitable fisheries requires nuanced policies not silver bullets'.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1335}, doi = {10.1038/s41559-018-0634-z}, pmid = {30038247}, issn = {2397-334X}, } @article {pmid30038246, year = {2018}, author = {Richardson, EJ and Bacigalupe, R and Harrison, EM and Weinert, LA and Lycett, S and Vrieling, M and Robb, K and Hoskisson, PA and Holden, MTG and Feil, EJ and Paterson, GK and Tong, SYC and Shittu, A and van Wamel, W and Aanensen, DM and Parkhill, J and Peacock, SJ and Corander, J and Holmes, M and Fitzgerald, JR}, title = {Gene exchange drives the ecological success of a multi-host bacterial pathogen.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1468-1478}, doi = {10.1038/s41559-018-0617-0}, pmid = {30038246}, issn = {2397-334X}, abstract = {The capacity for some pathogens to jump into different host-species populations is a major threat to public health and food security. Staphylococcus aureus is a multi-host bacterial pathogen responsible for important human and livestock diseases. Here, using a population-genomic approach, we identify humans as a major hub for ancient and recent S. aureus host-switching events linked to the emergence of endemic livestock strains, and cows as the main animal reservoir for the emergence of human epidemic clones. Such host-species transitions are associated with horizontal acquisition of genetic elements from host-specific gene pools conferring traits required for survival in the new host-niche. Importantly, genes associated with antimicrobial resistance are unevenly distributed among human and animal hosts, reflecting distinct antibiotic usage practices in medicine and agriculture. In addition to gene acquisition, genetic diversification has occurred in pathways associated with nutrient acquisition, implying metabolic remodelling after a host switch in response to distinct nutrient availability. For example, S. aureus from dairy cattle exhibit enhanced utilization of lactose-a major source of carbohydrate in bovine milk. Overall, our findings highlight the influence of human activities on the multi-host ecology of a major bacterial pathogen, underpinned by horizontal gene transfer and core genome diversification.}, } @article {pmid30038245, year = {2018}, author = {Cisneros-Montemayor, AM and Cashion, T and Miller, DD and Tai, TC and Talloni-Álvarez, N and Weiskel, HW and Sumaila, UR}, title = {Achieving sustainable and equitable fisheries requires nuanced policies not silver bullets.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1334}, doi = {10.1038/s41559-018-0633-0}, pmid = {30038245}, issn = {2397-334X}, } @article {pmid30038244, year = {2018}, author = {Courchamp, F and Bradshaw, CJA}, title = {Reply to 'Questionable survey methods generate a questionable list of recommended articles'.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1338-1339}, doi = {10.1038/s41559-018-0638-8}, pmid = {30038244}, issn = {2397-334X}, } @article {pmid30038243, year = {2018}, author = {Mayer, AL and Wellstead, AM}, title = {Questionable survey methods generate a questionable list of recommended articles.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1336-1337}, doi = {10.1038/s41559-018-0637-9}, pmid = {30038243}, issn = {2397-334X}, } @article {pmid30038030, year = {2018}, author = {Su, Z and Song, J and Wang, Z and Zhou, L and Xia, Y and Yu, S and Sun, Q and Liu, SS and Zhao, L and Li, S and Wei, L and Carson, DA and Lu, D}, title = {Tumor promoter TPA activates Wnt/β-catenin signaling in a casein kinase 1-dependent manner.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7522-E7531}, pmid = {30038030}, issn = {1091-6490}, mesh = {Animals ; Axin Protein/metabolism ; Carcinogenesis/chemically induced/pathology ; Carcinogens/*toxicity ; Casein Kinase Idelta/antagonists & inhibitors/*metabolism ; Casein Kinase Iepsilon/antagonists & inhibitors/*metabolism ; Cell Line, Tumor ; Disease Models, Animal ; Fibroblasts ; HEK293 Cells ; Humans ; Low Density Lipoprotein Receptor-Related Protein-6/metabolism ; Mice ; Phosphorylation ; Protein Stability/drug effects ; Purines/pharmacology ; Skin Neoplasms/chemically induced/*pathology ; Tetradecanoylphorbol Acetate/*toxicity ; Transcription Factor 4 ; Wnt Proteins/metabolism ; Wnt Signaling Pathway/*drug effects ; beta Catenin/metabolism ; }, abstract = {The tumor promoter 12-O-tetra-decanoylphorbol-13-acetate (TPA) has been defined by its ability to promote tumorigenesis on carcinogen-initiated mouse skin. Activation of Wnt/β-catenin signaling has a decisive role in mouse skin carcinogenesis, but it remains unclear how TPA activates Wnt/β-catenin signaling in mouse skin carcinogenesis. Here, we found that TPA could enhance Wnt/β-catenin signaling in a casein kinase 1 (CK1) ε/δ-dependent manner. TPA stabilized CK1ε and enhanced its kinase activity. TPA further induced the phosphorylation of LRP6 at Thr1479 and Ser1490 and the formation of a CK1ε-LRP6-axin1 complex, leading to an increase in cytosolic β-catenin. Moreover, TPA increased the association of β-catenin with TCF4E in a CK1ε/δ-dependent way, resulting in the activation of Wnt target genes. Consistently, treatment with a selective CK1ε/δ inhibitor SR3029 suppressed TPA-induced skin tumor formation in vivo, probably through blocking Wnt/β-catenin signaling. Taken together, our study has identified a pathway by which TPA activates Wnt/β-catenin signaling.}, } @article {pmid30038029, year = {2018}, author = {}, title = {Correction to Supporting Information for Hayashi et.al., Distinct requirements for energy metabolism in mouse primordial germ cells and their reprogramming to embryonic germ cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7232}, doi = {10.1073/pnas.1811451115}, pmid = {30038029}, issn = {1091-6490}, } @article {pmid30038028, year = {2018}, author = {Monroe, JI and Shell, MS}, title = {Computational discovery of chemically patterned surfaces that effect unique hydration water dynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8093-8098}, pmid = {30038028}, issn = {1091-6490}, abstract = {The interactions of water with solid surfaces govern their apparent hydrophobicity/hydrophilicity, influenced at the molecular scale by surface coverage of chemical groups of varied nonpolar/polar character. Recently, it has become clear that the precise patterning of surface groups, and not simply average surface coverage, has a significant impact on the structure and thermodynamics of hydration layer water, and, in turn, on macroscopic interfacial properties. Here we show that patterning also controls the dynamics of hydration water, a behavior frequently thought to be leveraged by biomolecules to influence functional dynamics, but yet to be generalized. To uncover the role of surface heterogeneities, we couple a genetic algorithm to iterative molecular dynamics simulations to design the patterning of surface functional groups, at fixed coverage, to either minimize or maximize proximal water diffusivity. Optimized surface configurations reveal that clustering of hydrophilic groups increases hydration water mobility, while dispersing them decreases it, but only if hydrophilic moieties interact with water through directional, hydrogen-bonding interactions. Remarkably, we find that, across different surfaces, coverages, and patterns, both the chemical potential for inserting a methane-sized hydrophobe near the interface and, in particular, the hydration water orientational entropy serve as strong predictors for hydration water diffusivity, suggesting that these simple thermodynamic quantities encode the way surfaces control water dynamics. These results suggest a deep and intriguing connection between hydration water thermodynamics and dynamics, demonstrating that subnanometer chemical surface patterning is an important design parameter for engineering solid-water interfaces with applications spanning separations to catalysis.}, } @article {pmid30038027, year = {2018}, author = {Soma, S and Latimer, AJ and Chun, H and Vicary, AC and Timbalia, SA and Boulet, A and Rahn, JJ and Chan, SSL and Leary, SC and Kim, BE and Gitlin, JD and Gohil, VM}, title = {Elesclomol restores mitochondrial function in genetic models of copper deficiency.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8161-8166}, pmid = {30038027}, issn = {1091-6490}, support = {R01 DK110195/DK/NIDDK NIH HHS/United States ; MOP 133562//CIHR/Canada ; R01 GM111672/GM/NIGMS NIH HHS/United States ; R01 DK044464/DK/NIDDK NIH HHS/United States ; R37 DK044464/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology/therapeutic use ; Biological Transport/genetics ; Carrier Proteins/genetics ; Cell Line ; Coenzymes/deficiency ; Copper/*deficiency/therapeutic use ; Dietary Supplements ; Disease Models, Animal ; Drug Repositioning ; Drugs, Investigational/*pharmacology/therapeutic use ; Electron Transport Complex IV/*metabolism ; Fibroblasts ; Humans ; Hydrazines/*pharmacology/therapeutic use ; Membrane Transport Proteins/genetics ; Metabolism, Inborn Errors/drug therapy/genetics/metabolism ; Mitochondria/*drug effects/metabolism ; Mitochondrial Proteins/genetics ; Mutagenesis, Site-Directed ; Mutation ; Rats ; Saccharomyces cerevisiae ; Zebrafish ; Zebrafish Proteins/genetics ; }, abstract = {Copper is an essential cofactor of cytochrome c oxidase (CcO), the terminal enzyme of the mitochondrial respiratory chain. Inherited loss-of-function mutations in several genes encoding proteins required for copper delivery to CcO result in diminished CcO activity and severe pathologic conditions in affected infants. Copper supplementation restores CcO function in patient cells with mutations in two of these genes, COA6 and SCO2, suggesting a potential therapeutic approach. However, direct copper supplementation has not been therapeutically effective in human patients, underscoring the need to identify highly efficient copper transporting pharmacological agents. By using a candidate-based approach, we identified an investigational anticancer drug, elesclomol (ES), that rescues respiratory defects of COA6-deficient yeast cells by increasing mitochondrial copper content and restoring CcO activity. ES also rescues respiratory defects in other yeast mutants of copper metabolism, suggesting a broader applicability. Low nanomolar concentrations of ES reinstate copper-containing subunits of CcO in a zebrafish model of copper deficiency and in a series of copper-deficient mammalian cells, including those derived from a patient with SCO2 mutations. These findings reveal that ES can restore intracellular copper homeostasis by mimicking the function of missing transporters and chaperones of copper, and may have potential in treating human disorders of copper metabolism.}, } @article {pmid30038026, year = {2018}, author = {Azar, Y and Horvitz, E and Lubetzky, E and Peres, Y and Shahaf, D}, title = {Tractable near-optimal policies for crawling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8099-8103}, doi = {10.1073/pnas.1801519115}, pmid = {30038026}, issn = {1091-6490}, abstract = {The problem of maintaining a local cache of n constantly changing pages arises in multiple mechanisms such as web crawlers and proxy servers. In these, the resources for polling pages for possible updates are typically limited. The goal is to devise a polling and fetching policy that maximizes the utility of served pages that are up to date. Cho and Garcia-Molina [(2003) ACM Trans Database Syst 28:390-426] formulated this as an optimization problem, which can be solved numerically for small values of n, but appears intractable in general. Here, we show that the optimal randomized policy can be found exactly in [Formula: see text] operations. Moreover, using the optimal probabilities to define in linear time a deterministic schedule yields a tractable policy that in experiments attains 99% of the optimum.}, } @article {pmid30038025, year = {2018}, author = {Karpitschka, S and Das, S and van Gorcum, M and Perrin, H and Andreotti, B and Snoeijer, JH}, title = {Soft wetting: Models based on energy dissipation or on force balance are equivalent.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7233}, pmid = {30038025}, issn = {1091-6490}, } @article {pmid30038024, year = {2018}, author = {Kleiner, S and Gomez, D and Megra, B and Na, E and Bhavsar, R and Cavino, K and Xin, Y and Rojas, J and Dominguez-Gutierrez, G and Zambrowicz, B and Carrat, G and Chabosseau, P and Hu, M and Murphy, AJ and Yancopoulos, GD and Rutter, GA and Gromada, J}, title = {Mice harboring the human SLC30A8 R138X loss-of-function mutation have increased insulin secretory capacity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7642-E7649}, pmid = {30038024}, issn = {1091-6490}, support = {MR/N00275X/1//Medical Research Council/United Kingdom ; MR/L020149/1//Medical Research Council/United Kingdom ; MR/K001981/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; MR/J0003042/1//Medical Research Council/United Kingdom ; WT098424AIA//Wellcome Trust/United Kingdom ; }, mesh = {Alleles ; Animals ; Blood Glucose ; Diabetes Mellitus, Type 2/*genetics/metabolism ; Disease Models, Animal ; Gene Knock-In Techniques ; Glucose/*metabolism ; Humans ; Hyperglycemia/blood/chemically induced/metabolism ; Insulin/*metabolism ; Insulin Secretion ; Insulin-Secreting Cells/*metabolism ; Loss of Function Mutation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Peptides/pharmacology ; Receptor, Insulin/antagonists & inhibitors/metabolism ; Zinc Transporter 8/*genetics/metabolism ; }, abstract = {SLC30A8 encodes a zinc transporter that is primarily expressed in the pancreatic islets of Langerhans. In β-cells it transports zinc into insulin-containing secretory granules. Loss-of-function (LOF) mutations in SLC30A8 protect against type 2 diabetes in humans. In this study, we generated a knockin mouse model carrying one of the most common human LOF mutations for SLC30A8, R138X. The R138X mice had normal body weight, glucose tolerance, and pancreatic β-cell mass. Interestingly, in hyperglycemic conditions induced by the insulin receptor antagonist S961, the R138X mice showed a 50% increase in insulin secretion. This effect was not associated with enhanced β-cell proliferation or mass. Our data suggest that the SLC30A8 R138X LOF mutation may exert beneficial effects on glucose metabolism by increasing the capacity of β-cells to secrete insulin under hyperglycemic conditions.}, } @article {pmid30038023, year = {2018}, author = {Díaz-Franulic, I and González-Pérez, V and Moldenhauer, H and Navarro-Quezada, N and Naranjo, D}, title = {Gating-induced large aqueous volumetric remodeling and aspartate tolerance in the voltage sensor domain of Shaker K+ channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8203-8208}, pmid = {30038023}, issn = {1091-6490}, mesh = {Action Potentials ; Amino Acid Sequence/genetics ; Animals ; Arginine/chemistry/genetics/metabolism ; Aspartic Acid/*chemistry/genetics ; Hydrophobic and Hydrophilic Interactions ; *Ion Channel Gating ; Molecular Dynamics Simulation ; Mutagenesis, Site-Directed ; Oocytes ; Osmosis ; Patch-Clamp Techniques ; *Protein Domains ; Shaker Superfamily of Potassium Channels/*chemistry/genetics ; Static Electricity ; Water/chemistry ; Xenopus ; }, abstract = {Neurons encode electrical signals with critically tuned voltage-gated ion channels and enzymes. Dedicated voltage sensor domains (VSDs) in these membrane proteins activate coordinately with an unresolved structural change. Such change conveys the transmembrane translocation of four positively charged arginine side chains, the voltage-sensing residues (VSRs; R1-R4). Countercharges and lipid phosphohead groups likely stabilize these VSRs within the low-dielectric core of the protein. However, the role of hydration, a sign-independent charge stabilizer, remains unclear. We replaced all VSRs and their neighboring residues with negatively charged aspartates in a voltage-gated potassium channel. The ensuing mild functional effects indicate that hydration is also important in VSR stabilization. The voltage dependency of the VSR aspartate variants approached the expected arithmetic summation of charges at VSR positions, as if negative and positive side chains faced similar pathways. In contrast, aspartates introduced between R2 and R3 did not affect voltage dependence as if the side chains moved outside the electric field or together with it, undergoing a large displacement and volumetric remodeling. Accordingly, VSR performed osmotic work at both internal and external aqueous interfaces. Individual VSR contributions to volumetric works approached arithmetical additivity but were largely dissimilar. While R1 and R4 displaced small volumes, R2 and R3 volumetric works were massive and vectorially opposed, favoring large aqueous remodeling during VSD activation. These diverse volumetric works are, at least for R2 and R3, not compatible with VSR translocation across a unique stationary charge transfer center. Instead, VSRs may follow separated pathways across a fluctuating low-dielectric septum.}, } @article {pmid30038022, year = {2018}, author = {Zhao, M and Dervaux, J and Narita, T and Lequeux, F and Limat, L and Roché, M}, title = {Reply to Karpitschka et al.: The Neumann force balance does not hold in dynamical elastowetting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7234-E7235}, pmid = {30038022}, issn = {1091-6490}, } @article {pmid30038021, year = {2018}, author = {Medinas, DB and Rozas, P and Martínez Traub, F and Woehlbier, U and Brown, RH and Bosco, DA and Hetz, C}, title = {Endoplasmic reticulum stress leads to accumulation of wild-type SOD1 aggregates associated with sporadic amyotrophic lateral sclerosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8209-8214}, pmid = {30038021}, issn = {1091-6490}, support = {R01 NS067206/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Aging/pathology ; Amyotrophic Lateral Sclerosis/genetics/*pathology ; Animals ; Astrocytes/pathology ; Brain/cytology/drug effects/pathology ; Cell Line ; Disease Models, Animal ; Endoplasmic Reticulum Stress/drug effects/*physiology ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Middle Aged ; Motor Neurons ; Mutation ; Oxidation-Reduction ; Protein Aggregation, Pathological/genetics/pathology ; Protein Folding ; Proteostasis/physiology ; Spinal Cord/cytology/drug effects/*pathology ; Superoxide Dismutase-1/genetics/*metabolism ; Tryptophan/metabolism ; Tunicamycin/pharmacology ; Unfolded Protein Response/physiology ; }, abstract = {Abnormal modifications to mutant superoxide dismutase 1 (SOD1) are linked to familial amyotrophic lateral sclerosis (fALS). Misfolding of wild-type SOD1 (SOD1WT) is also observed in postmortem tissue of a subset of sporadic ALS (sALS) cases, but cellular and molecular mechanisms generating abnormal SOD1WT species are unknown. We analyzed aberrant human SOD1WT species over the lifetime of transgenic mice and found the accumulation of disulfide-cross-linked high-molecular-weight SOD1WT aggregates during aging. Subcellular fractionation of spinal cord tissue and protein overexpression in NSC-34 motoneuron-like cells revealed that endoplasmic reticulum (ER) localization favors oxidation and disulfide-dependent aggregation of SOD1WT We established a pharmacological paradigm of chronic ER stress in vivo, which recapitulated SOD1WTaggregation in young transgenic mice. These species were soluble in nondenaturing detergents and did not react with a SOD1 conformation-specific antibody. Interestingly, SOD1WT aggregation under ER stress correlated with astrocyte activation in the spinal cord of transgenic mice. Finally, the disulfide-cross-linked SOD1WT species were also found augmented in spinal cord tissue of sALS patients, correlating with the presence of ER stress markers. Overall, this study suggests that ER stress increases the susceptibility of SOD1WT to aggregate during aging, operating as a possible risk factor for developing ALS.}, } @article {pmid30038020, year = {2018}, author = {Smith, Q and Rochman, N and Carmo, AM and Vig, D and Chan, XY and Sun, S and Gerecht, S}, title = {Cytoskeletal tension regulates mesodermal spatial organization and subsequent vascular fate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8167-8172}, pmid = {30038020}, issn = {1091-6490}, support = {F31 HL134329/HL/NHLBI NIH HHS/United States ; U54 CA210173/CA/NCI NIH HHS/United States ; }, mesh = {Body Patterning/*physiology ; Cell Differentiation/physiology ; Cell Lineage/*physiology ; Cells, Cultured ; Cytoskeleton/*physiology ; Endothelial Cells/physiology ; Fetal Proteins/metabolism ; Fluorescent Antibody Technique/methods ; Humans ; Image Processing, Computer-Assisted ; Induced Pluripotent Stem Cells/*physiology ; Machine Learning ; Mesoderm/cytology/*physiopathology ; Pericytes/physiology ; Stem Cell Niche/physiology ; Stress, Mechanical ; T-Box Domain Proteins/metabolism ; rho-Associated Kinases/metabolism ; rhoA GTP-Binding Protein/metabolism ; }, abstract = {Morphogenesis during human development relies on the interplay between physiochemical cues that are mediated in part by cellular density and cytoskeletal tension. Here, we interrogated these factors on vascular lineage specification during human-induced pluripotent stem-cell (hiPSC) fate decision. We found that independent of chemical cues, spatially presented physical cues induce the self-organization of Brachyury-positive mesodermal cells, in a RhoA/Rho-associated kinase (ROCK)-dependent manner. Using unbiased support vector machine (SVM) learning, we found that density alone is sufficient to predict mesodermal fate. Furthermore, the long-withstanding presentation of spatial confinement during hiPSC differentiation led to an organized vascular tissue, reminiscent of native blood vessels, a process dependent on cell density as found by SVM analysis. Collectively, these results show how tension and density relate to vascular identity mirroring early morphogenesis. We propose that such a system can be applied to study other aspects of the stem-cell niche and its role in embryonic patterning.}, } @article {pmid30038019, year = {2018}, author = {Bertagni, MB and Perona, P and Camporeale, C}, title = {Parametric transitions between bare and vegetated states in water-driven patterns.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8125-8130}, pmid = {30038019}, issn = {1091-6490}, mesh = {*Competitive Behavior ; Ecosystem ; Geologic Sediments ; *Geological Phenomena ; Hydrodynamics ; *Models, Biological ; Plant Development/*physiology ; Population Dynamics ; Rivers ; Soil ; Species Specificity ; Stochastic Processes ; Water ; }, abstract = {Conditions for vegetation spreading and pattern formation are mathematically framed through an analysis encompassing three fundamental processes: flow stochasticity, vegetation dynamics, and sediment transport. Flow unsteadiness is included through Poisson stochastic processes whereby vegetation dynamics appears as a secondary instability, which is addressed by Floquet theory. Results show that the model captures the physical conditions heralding the transition between bare and vegetated fluvial states where the nonlinear formation and growth of finite alternate bars are accounted for by Center Manifold Projection. This paves the way to understand changes in biogeomorphological styles induced by man in the Anthropocene and of natural origin since the Paleozoic (Devonian plant hypothesis).}, } @article {pmid30038018, year = {2018}, author = {Bello, OD and Jouannot, O and Chaudhuri, A and Stroeva, E and Coleman, J and Volynski, KE and Rothman, JE and Krishnakumar, SS}, title = {Synaptotagmin oligomerization is essential for calcium control of regulated exocytosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7624-E7631}, pmid = {30038018}, issn = {1091-6490}, support = {R01 DK027044/DK/NIDDK NIH HHS/United States ; T32 GM007223/GM/NIGMS NIH HHS/United States ; 104033//Wellcome Trust/United Kingdom ; R37 DK027044/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Calcium/*metabolism ; Cations, Divalent/metabolism ; Cytoplasmic Vesicles/metabolism/ultrastructure ; *Exocytosis ; Fluorescent Antibody Technique ; Green Fluorescent Proteins/chemistry ; Membrane Fusion/*physiology ; Microscopy, Electron ; Mutation ; PC12 Cells ; Protein Binding/physiology ; Protein Multimerization/*physiology ; Rats ; Recombinant Proteins/metabolism ; Synaptotagmin I/genetics/*metabolism ; Vesicle-Associated Membrane Protein 2/metabolism ; }, abstract = {Regulated exocytosis, which underlies many intercellular signaling events, is a tightly controlled process often triggered by calcium ion(s) (Ca2+). Despite considerable insight into the central components involved, namely, the core fusion machinery [soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)] and the principal Ca2+ sensor [C2-domain proteins like synaptotagmin (Syt)], the molecular mechanism of Ca2+-dependent release has been unclear. Here, we report that the Ca2+-sensitive oligomers of Syt1, a conserved structural feature among several C2-domain proteins, play a critical role in orchestrating Ca2+-coupled vesicular release. This follows from pHluorin-based imaging of single-vesicle exocytosis in pheochromocytoma (PC12) cells showing that selective disruption of Syt1 oligomerization using a structure-directed mutation (F349A) dramatically increases the normally low levels of constitutive exocytosis to effectively occlude Ca2+-stimulated release. We propose a parsimonious model whereby Ca2+-sensitive oligomers of Syt (or a similar C2-domain protein) assembled at the site of docking physically block spontaneous fusion until disrupted by Ca2+ Our data further suggest Ca2+-coupled vesicular release is triggered by removal of the inhibition, rather than by direct activation of the fusion machinery.}, } @article {pmid30038017, year = {2018}, author = {Kincaid, RP and Lam, VL and Chirayil, RP and Randall, G and Sullivan, CS}, title = {RNA triphosphatase DUSP11 enables exonuclease XRN-mediated restriction of hepatitis C virus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8197-8202}, pmid = {30038017}, issn = {1091-6490}, support = {R01 DK102883/DK/NIDDK NIH HHS/United States ; }, mesh = {Acid Anhydride Hydrolases/genetics/*metabolism ; Carcinoma, Hepatocellular/genetics/virology ; Cell Line, Tumor ; Dual-Specificity Phosphatases/genetics/*metabolism ; Exoribonucleases/genetics/*metabolism ; Gene Knockout Techniques ; Genome, Viral ; Hepacivirus/*pathogenicity/physiology ; Hepatitis C, Chronic/genetics/virology ; Hepatocytes/virology ; Host-Pathogen Interactions/*physiology ; Humans ; Liver Neoplasms/genetics/virology ; MicroRNAs/*metabolism ; RNA, Small Interfering/metabolism ; RNA, Viral/metabolism ; Virus Replication/genetics ; }, abstract = {Seventy percent of people infected with hepatitis C virus (HCV) will suffer chronic infection, putting them at risk for liver disease, including hepatocellular carcinoma. The full range of mechanisms that render some people more susceptible to chronic infection and liver disease is still being elucidated. XRN exonucleases can restrict HCV replication and may help to resolve HCV infections. However, it is unknown how 5' triphosphorylated HCV transcripts, primary products of the viral polymerase, become susceptible to attack by 5' monophosphate-specific XRNs. Here, we show that the 5' RNA triphosphatase DUSP11 acts on HCV transcripts, rendering them susceptible to XRN-mediated attack. Cells lacking DUSP11 show substantially enhanced HCV replication, and this effect is diminished when XRN expression is reduced. MicroRNA-122 (miR-122), a target of current phase II anti-HCV drugs, is known to protect HCV transcripts against XRNs. We show that HCV replication is less dependent on miR-122 in cells lacking DUSP11. Combined, these results implicate DUSP11 as an important component of XRN-mediated restriction of HCV.}, } @article {pmid30038016, year = {2018}, author = {England, JP and Hao, Y and Bai, L and Glick, V and Hodges, HC and Taylor, SS and Maillard, RA}, title = {Switching of the folding-energy landscape governs the allosteric activation of protein kinase A.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7478-E7485}, pmid = {30038016}, issn = {1091-6490}, support = {R00 CA187565/CA/NCI NIH HHS/United States ; R01 GM034921/GM/NIGMS NIH HHS/United States ; }, mesh = {Allosteric Regulation/physiology ; Catalytic Domain/genetics/*physiology ; Cyclic AMP/chemistry/*metabolism ; Cyclic AMP-Dependent Protein Kinases/chemistry/*metabolism ; Enzyme Assays ; Molecular Dynamics Simulation ; Mutation ; Optical Tweezers ; Protein Binding/physiology ; Protein Domains/physiology ; *Protein Folding ; Signal Transduction/*physiology ; }, abstract = {Protein kinases are dynamic molecular switches that sample multiple conformational states. The regulatory subunit of PKA harbors two cAMP-binding domains [cyclic nucleotide-binding (CNB) domains] that oscillate between inactive and active conformations dependent on cAMP binding. The cooperative binding of cAMP to the CNB domains activates an allosteric interaction network that enables PKA to progress from the inactive to active conformation, unleashing the activity of the catalytic subunit. Despite its importance in the regulation of many biological processes, the molecular mechanism responsible for the observed cooperativity during the activation of PKA remains unclear. Here, we use optical tweezers to probe the folding cooperativity and energetics of domain communication between the cAMP-binding domains in the apo state and bound to the catalytic subunit. Our study provides direct evidence of a switch in the folding-energy landscape of the two CNB domains from energetically independent in the apo state to highly cooperative and energetically coupled in the presence of the catalytic subunit. Moreover, we show that destabilizing mutational effects in one CNB domain efficiently propagate to the other and decrease the folding cooperativity between them. Taken together, our results provide a thermodynamic foundation for the conformational plasticity that enables protein kinases to adapt and respond to signaling molecules.}, } @article {pmid30038015, year = {2018}, author = {Bonsma-Fisher, M and Soutière, D and Goyal, S}, title = {How adaptive immunity constrains the composition and fate of large bacterial populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7462-E7468}, pmid = {30038015}, issn = {1091-6490}, mesh = {Adaptive Immunity/*physiology ; Bacteria/genetics/*immunology/virology ; Bacteriophages/genetics/*immunology ; CRISPR-Cas Systems/*immunology ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics/immunology ; DNA, Viral/genetics/immunology ; Evolution, Molecular ; Quorum Sensing/*immunology ; }, abstract = {Features of the CRISPR-Cas system, in which bacteria integrate small segments of phage genome (spacers) into their DNA to neutralize future attacks, suggest that its effect is not limited to individual bacteria but may control the fate and structure of whole populations. Emphasizing the population-level impact of the CRISPR-Cas system, recent experiments show that some bacteria regulate CRISPR-associated genes via the quorum sensing (QS) pathway. Here we present a model that shows that from the highly stochastic dynamics of individual spacers under QS control emerges a rank-abundance distribution of spacers that is time invariant, a surprising prediction that we test with dynamic spacer-tracking data from literature. This distribution depends on the state of the competing phage-bacteria population, which due to QS-based regulation may coexist in multiple stable states that vary significantly in their phage-to-bacterium ratio, a widely used ecological measure to characterize microbial systems.}, } @article {pmid30038014, year = {2018}, author = {}, title = {Correction for Touboul et al., On the complex dynamics of savanna landscapes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7457}, doi = {10.1073/pnas.1810993115}, pmid = {30038014}, issn = {1091-6490}, } @article {pmid30038013, year = {2018}, author = {Deng, W and Lira, V and Hudson, TE and Lemmens, EE and Hanson, WG and Flores, R and Barajas, G and Katibah, GE and Desbien, AL and Lauer, P and Leong, ML and Portnoy, DA and Dubensky, TW}, title = {Recombinant Listeria promotes tumor rejection by CD8+ T cell-dependent remodeling of the tumor microenvironment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8179-8184}, pmid = {30038013}, issn = {1091-6490}, support = {P01 AI063302/AI/NIAID NIH HHS/United States ; R01 AI027655/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigens, Neoplasm/genetics/*immunology/therapeutic use ; CD8-Positive T-Lymphocytes/*immunology ; Cancer Vaccines/genetics/*immunology/therapeutic use ; Cell Line, Tumor ; Drug Evaluation, Preclinical ; Female ; Humans ; Listeria monocytogenes/genetics/*immunology ; Macrophages/immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms/immunology/*therapy ; Treatment Outcome ; Tumor Microenvironment/*immunology ; Vaccination/methods ; Vaccines, Attenuated/genetics/immunology/therapeutic use ; Vaccines, DNA/genetics/immunology/therapeutic use ; Xenograft Model Antitumor Assays ; }, abstract = {Agents that remodel the tumor microenvironment (TME), prime functional tumor-specific T cells, and block inhibitory signaling pathways are essential components of effective immunotherapy. We are evaluating live-attenuated, double-deleted Listeria monocytogenes expressing tumor antigens (LADD-Ag) in the clinic. Here we show in numerous mouse models that while treatment with nonrecombinant LADD induced some changes in the TME, no antitumor efficacy was observed, even when combined with immune checkpoint blockade. In contrast, LADD-Ag promoted tumor rejection by priming tumor-specific KLRG1+PD1loCD62L- CD8+ T cells. These IFNγ-producing effector CD8+ T cells infiltrated the tumor and converted the tumor from an immunosuppressive to an inflamed microenvironment that was characterized by a decrease in regulatory T cells (Treg) levels, a proinflammatory cytokine milieu, and the shift of M2 macrophages to an inducible nitric oxide synthase (iNOS)+CD206- M1 phenotype. Remarkably, these LADD-Ag-induced tumor-specific T cells persisted for more than 2 months after primary tumor challenge and rapidly controlled secondary tumor challenge. Our results indicate that the striking antitumor efficacy observed in mice with LADD-based immunotherapy stems from TME remodeling which is a direct consequence of eliciting potent, systemic tumor-specific CD8+ T cells.}, } @article {pmid30038012, year = {2018}, author = {Cully, TR and Choi, RH and Bjorksten, AR and Stephenson, DG and Murphy, RM and Launikonis, BS}, title = {Junctional membrane Ca2+ dynamics in human muscle fibers are altered by malignant hyperthermia causative RyR mutation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8215-8220}, pmid = {30038012}, issn = {1091-6490}, mesh = {Adult ; Biopsy ; Calcium/chemistry/*metabolism ; Cations, Divalent/chemistry/metabolism ; Cell Membrane/metabolism/pathology ; Female ; Fluorescent Dyes/chemistry ; Humans ; Intercellular Junctions/metabolism/*pathology ; Male ; Malignant Hyperthermia/genetics/*pathology ; Mutation ; Nanostructures/chemistry ; Ryanodine Receptor Calcium Release Channel/*genetics/metabolism ; Sarcoplasmic Reticulum/metabolism/*pathology ; Young Adult ; }, abstract = {We used the nanometer-wide tubules of the transverse tubular (t)-system of human skeletal muscle fibers as sensitive sensors for the quantitative monitoring of the Ca2+-handling properties in the narrow junctional cytoplasmic space sandwiched between the tubular membrane and the sarcoplasmic reticulum cisternae in single muscle fibers. The t-system sealed with a Ca2+-sensitive dye trapped in it is sensitive to changes in ryanodine receptor (RyR) Ca2+ leak, the store operated calcium entry flux, plasma membrane Ca pump, and sodium-calcium exchanger activities, thus making the sealed t-system a nanodomain Ca2+ sensor of Ca2+ dynamics in the junctional space. The sensor was used to assess the basal Ca2+-handling properties of human muscle fibers obtained by needle biopsy from control subjects and from people with a malignant hyperthermia (MH) causative RyR variant. Using this approach we show that the muscle fibers from MH-susceptible individuals display leakier RyRs and a greater capacity to extrude Ca2+ across the t-system membrane compared with fibers from controls. This study provides a quantitative way to assess the effect of RyR variants on junctional membrane Ca2+ handling under defined ionic conditions.}, } @article {pmid30038011, year = {2018}, author = {Koltz, AM and Classen, AT and Wright, JP}, title = {Warming reverses top-down effects of predators on belowground ecosystem function in Arctic tundra.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7541-E7549}, pmid = {30038011}, issn = {1091-6490}, mesh = {Animals ; Arctic Regions ; Biomass ; Carbon Cycle ; *Food Chain ; Fungi/chemistry/physiology ; *Global Warming ; Insecta/physiology ; Nitrogen/chemistry ; Soil/*chemistry ; *Soil Microbiology ; Spiders/physiology ; *Tundra ; }, abstract = {Predators can disproportionately impact the structure and function of ecosystems relative to their biomass. These effects may be exacerbated under warming in ecosystems like the Arctic, where the number and diversity of predators are low and small shifts in community interactions can alter carbon cycle feedbacks. Here, we show that warming alters the effects of wolf spiders, a dominant tundra predator, on belowground litter decomposition. Specifically, while high densities of wolf spiders result in faster litter decomposition under ambient temperatures, they result, instead, in slower decomposition under warming. Higher spider densities are also associated with elevated levels of available soil nitrogen, potentially benefiting plant production. Changes in decomposition rates under increased wolf spider densities are accompanied by trends toward fewer fungivorous Collembola under ambient temperatures and more Collembola under warming, suggesting that Collembola mediate the indirect effects of wolf spiders on decomposition. The unexpected reversal of wolf spider effects on Collembola and decomposition suggest that in some cases, warming does not simply alter the strength of top-down effects but, instead, induces a different trophic cascade altogether. Our results indicate that climate change-induced effects on predators can cascade through other trophic levels, alter critical ecosystem functions, and potentially lead to climate feedbacks with important global implications. Moreover, given the expected increase in wolf spider densities with climate change, our findings suggest that the observed cascading effects of this common predator on detrital processes could potentially buffer concurrent changes in decomposition rates.}, } @article {pmid30038010, year = {2018}, author = {Datta, S and Misra, SK and Saha, ML and Lahiri, N and Louie, J and Pan, D and Stang, PJ}, title = {Orthogonal self-assembly of an organoplatinum(II) metallacycle and cucurbit[8]uril that delivers curcumin to cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8087-8092}, pmid = {30038010}, issn = {1091-6490}, support = {R01 CA215157/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*chemistry/*pharmacology ; Apoptosis/drug effects ; Biocompatible Materials/chemistry/pharmacology ; Biological Availability ; Breast Neoplasms ; Bridged-Ring Compounds/*chemistry/*pharmacology ; Cell Line, Tumor/drug effects ; Cell Survival/drug effects ; Curcuma/chemistry ; Curcumin/*chemistry/*pharmacology ; Drug Delivery Systems ; Humans ; Imidazoles/*chemistry/*pharmacology ; Inhibitory Concentration 50 ; MCF-7 Cells ; Melanoma ; Molecular Structure ; Organoplatinum Compounds/*chemistry/*pharmacology ; Paraquat ; Rodentia ; STAT3 Transcription Factor/metabolism ; Solubility ; Water/chemistry ; }, abstract = {Curcumin (Cur) is a naturally occurring anticancer drug isolated from the Curcuma longa plant. It is known to exhibit anticancer properties via inhibiting the STAT3 phosphorylation process. However, its poor water solubility and low bioavailability impede its clinical application. Herein, we used organoplatinum(II) ← pyridyl coordination-driven self-assembly and a cucurbit[8]uril (CB[8])-mediated heteroternary host-guest complex formation in concert to produce an effective delivery system that transports Cur into the cancer cells. Specifically, a hexagon 1, containing hydrophilic methyl viologen (MV) units and 3,4,5-Tris[2-[2-(2-methoxyethoxy)ethoxy]ethoxy]benzoyl groups alternatively at the vertices, has been synthesized and characterized by several spectroscopic techniques. The MV units of 1 underwent noncovalent complexation with CB[8] to yield a host-guest complex 4. Cur can be encapsulated in 4, via a 1:1:1 heteroternary complex formation, resulting in a water-soluble host-guest complex 5. The host-guest complex 5 exhibited ca 100-fold improved IC50 values relative to free Cur against human melanoma (C32), melanoma of rodents (B16F10), and hormone-responsive (MCF-7) and triple-negative (MDA-MB231) breast cancer cells. Moreover, strong synergisms of Cur with 1 and 4 with combinatorial indexes of <1 across all of the cell lines were observed. An induced apoptosis with fragmented DNA pattern and inhibited expression of phosphor-STAT3 supported the improved therapeutic potential of Cur in heteroternary complex 5.}, } @article {pmid30038009, year = {2018}, author = {Bellefroid, EJ and Hood, AVS and Hoffman, PF and Thomas, MD and Reinhard, CT and Planavsky, NJ}, title = {Constraints on Paleoproterozoic atmospheric oxygen levels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8104-8109}, pmid = {30038009}, issn = {1091-6490}, abstract = {The oxygenation of Earth's surface environment dramatically altered key biological and geochemical cycles and ultimately ushered in the rise of an ecologically diverse biosphere. However, atmospheric oxygen partial pressures (pO2) estimates for large swaths of the Precambrian remain intensely debated. Here we evaluate and explore the use of carbonate cerium (Ce) anomalies (Ce/Ce*) as a quantitative atmospheric pO2 proxy and provide estimates of Proterozoic pO2 using marine carbonates from a unique Precambrian carbonate succession-the Paleoproterozoic Pethei Group. In contrast to most previous work, we measure Ce/Ce* on marine carbonate precipitates that formed in situ across a depth gradient, building on previous detailed sedimentology and stratigraphy to constrain the paleo-depth of each sample. Measuring Ce/Ce* across a full platform to basin depth gradient, we found only minor depleted Ce anomalies restricted to the platform and upper slope facies. We combine these results with a Ce oxidation model to provide a quantitative constraint on atmospheric pO2 1.87 billion years ago (Ga). Our results suggest Paleoproterozoic atmospheric oxygen concentrations were low, near 0.1% of the present atmospheric level. This work provides another crucial line of empirical evidence that atmospheric oxygen levels returned to low concentrations following the Lomagundi Event, and remained low enough for large portions of the Proterozoic to have impacted the ecology of the earliest complex organisms.}, } @article {pmid30038008, year = {2018}, author = {Sakabe, S and Sullivan, BM and Hartnett, JN and Robles-Sikisaka, R and Gangavarapu, K and Cubitt, B and Ware, BC and Kotliar, D and Branco, LM and Goba, A and Momoh, M and Sandi, JD and Kanneh, L and Grant, DS and Garry, RF and Andersen, KG and de la Torre, JC and Sabeti, PC and Schieffelin, JS and Oldstone, MBA}, title = {Analysis of CD8+ T cell response during the 2013-2016 Ebola epidemic in West Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7578-E7586}, pmid = {30038008}, issn = {1091-6490}, support = {HHSN272201400048C/AI/NIAID NIH HHS/United States ; U19 AI135995/AI/NIAID NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Antibodies, Viral/blood/*immunology ; Antigens, Viral/immunology ; CD8-Positive T-Lymphocytes/*immunology ; Ebolavirus/*immunology ; *Epidemics ; Epitopes, T-Lymphocyte/immunology ; Female ; HLA Antigens/blood/*immunology ; Hemorrhagic Fever, Ebola/blood/epidemiology/*immunology/prevention & control ; Humans ; Male ; Nucleoproteins/immunology ; Sierra Leone ; Survivors ; Vaccination/methods ; Viral Proteins/immunology ; Young Adult ; }, abstract = {The recent Ebola epidemic exemplified the importance of understanding and controlling emerging infections. Despite the importance of T cells in clearing virus during acute infection, little is known about Ebola-specific CD8+ T cell responses. We investigated immune responses of individuals infected with Ebola virus (EBOV) during the 2013-2016 West Africa epidemic in Sierra Leone, where the majority of the >28,000 EBOV disease (EVD) cases occurred. We examined T cell memory responses to seven of the eight Ebola proteins (GP, sGP, NP, VP24, VP30, VP35, and VP40) and associated HLA expression in survivors. Of the 30 subjects included in our analysis, CD8+ T cells from 26 survivors responded to at least one EBOV antigen. A minority, 10 of 26 responders (38%), made CD8+ T cell responses to the viral GP or sGP. In contrast, 25 of the 26 responders (96%) made response to viral NP, 77% to VP24 (20 of 26), 69% to VP40 (18 of 26), 42% (11 of 26) to VP35, with no response to VP30. Individuals making CD8+ T cells to EBOV VP24, VP35, and VP40 also made CD8+ T cells to NP, but rarely to GP. We identified 34 CD8+ T cell epitopes for Ebola. Our data indicate the immunodominance of the EBOV NP-specific T cell response and suggest that its inclusion in a vaccine along with the EBOV GP would best mimic survivor responses and help boost cell-mediated immunity during vaccination.}, } @article {pmid30038007, year = {2018}, author = {Morelli, SA and Leong, YC and Carlson, RW and Kullar, M and Zaki, J}, title = {Neural detection of socially valued community members.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8149-8154}, pmid = {30038007}, issn = {1091-6490}, support = {F32 MH098504/MH/NIMH NIH HHS/United States ; R21 MH104464/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Brain/*physiopathology ; Empathy ; Female ; Friends ; Humans ; Male ; Neuroimaging/*methods ; Peer Group ; *Social Behavior ; *Social Networking ; Social Perception ; *Social Values ; Theory of Mind ; }, abstract = {As people form social groups, they benefit from being able to detect socially valuable community members-individuals who act prosocially, support others, and form strong relationships. Multidisciplinary evidence demonstrates that people indeed track others' social value, but the mechanisms through which such detection occurs remain unclear. Here, we combine social network and neuroimaging analyses to examine this process. We mapped social networks in two freshman dormitories (n = 97), identifying how often individuals were nominated as socially valuable (i.e., sources of friendship, empathy, and support) by their peers. Next, we scanned a subset of dorm members ("perceivers"; n = 50) as they passively viewed photos of their dormmates ("targets"). Perceiver brain activity in regions associated with mentalizing and value computation differentiated between highly valued targets and other community members but did not differentiate between targets with middle versus low levels of social value. Cross-validation analysis revealed that brain activity from novel perceivers could be used to accurately predict whether targets viewed by those perceivers were high in social value or not. These results held even after controlling for perceivers' own ratings of closeness to targets, and even though perceivers were not directed to focus on targets' social value. Overall, these findings demonstrate that individuals spontaneously monitor people identified as sources of strong connection in the broader community.}, } @article {pmid30038006, year = {2018}, author = {Azar, B}, title = {Profile of Myles Brown.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8054-8056}, pmid = {30038006}, issn = {1091-6490}, mesh = {Chromosome Mapping ; Gonadal Steroid Hormones ; History, 20th Century ; History, 21st Century ; Humans ; Oncologists/*history ; Receptors, Estrogen ; United States ; }, } @article {pmid30038005, year = {2018}, author = {Severo, MS and Landry, JJM and Lindquist, RL and Goosmann, C and Brinkmann, V and Collier, P and Hauser, AE and Benes, V and Henriksson, J and Teichmann, SA and Levashina, EA}, title = {Unbiased classification of mosquito blood cells by single-cell genomics and high-content imaging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7568-E7577}, pmid = {30038005}, issn = {1091-6490}, mesh = {Animals ; Animals, Genetically Modified ; Anopheles/*genetics/immunology ; Blood Cells/*classification/immunology ; Cell Communication/genetics ; Cell Plasticity/*genetics ; Datasets as Topic ; Female ; Genomics/methods ; Malaria/*transmission ; Mosquito Vectors/*genetics/immunology ; RNA/genetics ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Transcriptome ; }, abstract = {Mosquito blood cells are immune cells that help control infection by vector-borne pathogens. Despite their importance, little is known about mosquito blood cell biology beyond morphological and functional criteria used for their classification. Here, we combined the power of single-cell RNA sequencing, high-content imaging flow cytometry, and single-molecule RNA hybridization to analyze a subset of blood cells of the malaria mosquito Anopheles gambiae By demonstrating that blood cells express nearly half of the mosquito transcriptome, our dataset represents an unprecedented view into their transcriptional program. Analyses of differentially expressed genes identified transcriptional signatures of two cell types and provide insights into the current classification of these cells. We further demonstrate the active transfer of a cellular marker between blood cells that may confound their identification. We propose that cell-to-cell exchange may contribute to cellular diversity and functional plasticity seen across biological systems.}, } @article {pmid30038004, year = {2018}, author = {Liu, G and Gong, J and Kong, L and Schaller, RD and Hu, Q and Liu, Z and Yan, S and Yang, W and Stoumpos, CC and Kanatzidis, MG and Mao, HK and Xu, T}, title = {Isothermal pressure-derived metastable states in 2D hybrid perovskites showing enduring bandgap narrowing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8076-8081}, pmid = {30038004}, issn = {1091-6490}, abstract = {Materials in metastable states, such as amorphous ice and supercooled condensed matter, often exhibit exotic phenomena. To date, achieving metastability is usually accomplished by rapid quenching through a thermodynamic path function, namely, heating-cooling cycles. However, heat can be detrimental to organic-containing materials because it can induce degradation. Alternatively, the application of pressure can be used to achieve metastable states that are inaccessible via heating-cooling cycles. Here we report metastable states of 2D organic-inorganic hybrid perovskites reached through structural amorphization under compression followed by recrystallization via decompression. Remarkably, such pressure-derived metastable states in 2D hybrid perovskites exhibit enduring bandgap narrowing by as much as 8.2% with stability under ambient conditions. The achieved metastable states in 2D hybrid perovskites via compression-decompression cycles offer an alternative pathway toward manipulating the properties of these "soft" materials.}, } @article {pmid30038003, year = {2018}, author = {Jing, Z and Liu, C and Qi, R and Ren, P}, title = {Many-body effect determines the selectivity for Ca2+ and Mg2+ in proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7495-E7501}, pmid = {30038003}, issn = {1091-6490}, support = {R01 GM106137/GM/NIGMS NIH HHS/United States ; R01 GM114237/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Calcium/*metabolism ; Calcium-Binding Proteins/*metabolism ; Ions/metabolism ; Magnesium/*metabolism ; *Molecular Dynamics Simulation ; Protein Binding ; Static Electricity ; }, abstract = {Calcium ion is a versatile messenger in many cell-signaling processes. To achieve their functions, calcium-binding proteins selectively bind Ca2+ against a background of competing ions such as Mg2+ The high specificity of calcium-binding proteins has been intriguing since Mg2+ has a higher charge density than Ca2+ and is expected to bind more tightly to the carboxylate groups in calcium-binding pockets. Here, we showed that the specificity for Ca2+ is dictated by the many-body polarization effect, which is an energetic cost arising from the dense packing of multiple residues around the metal ion. Since polarization has stronger distance dependence compared with permanent electrostatics, the cost associated with the smaller Mg2+ is much higher than that with Ca2+ and outweighs the electrostatic attraction favorable for Mg2+ With the AMOEBA (atomic multipole optimized energetics for biomolecular simulation) polarizable force field, our simulations captured the relative binding free energy between Ca2+ and Mg2+ for proteins with various types of binding pockets and explained the nonmonotonic size dependence of the binding free energy in EF-hand proteins. Without electronic polarization, the smaller ions are always favored over larger ions and the relative binding free energy is roughly proportional to the net charge of the pocket. The many-body effect depends on both the number and the arrangement of charged residues. Fine-tuning of the ion selectivity could be achieved by combining the many-body effect and geometric constraint.}, } @article {pmid30038002, year = {2018}, author = {Li, Y and Sharma, MR and Koripella, RK and Yang, Y and Kaushal, PS and Lin, Q and Wade, JT and Gray, TA and Derbyshire, KM and Agrawal, RK and Ojha, AK}, title = {Zinc depletion induces ribosome hibernation in mycobacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8191-8196}, pmid = {30038002}, issn = {1091-6490}, support = {R21 AI107595/AI/NIAID NIH HHS/United States ; P41 GM103310/GM/NIGMS NIH HHS/United States ; R01 GM061576/GM/NIGMS NIH HHS/United States ; R01 AI132422/AI/NIAID NIH HHS/United States ; R01 AI097191/AI/NIAID NIH HHS/United States ; }, mesh = {Aminoglycosides/pharmacology ; Animals ; Antibiotics, Antitubercular/*pharmacology ; Bacterial Proteins/*metabolism ; Cryoelectron Microscopy ; Disease Models, Animal ; Drug Resistance, Bacterial ; Female ; Humans ; Mice ; Mice, Inbred C57BL ; Microbial Sensitivity Tests ; Models, Molecular ; Mycobacterium smegmatis/drug effects/physiology ; Mycobacterium tuberculosis/drug effects/*physiology ; Protein Biosynthesis/physiology ; Ribosomal Proteins/*metabolism ; Ribosomes/metabolism/ultrastructure ; Tuberculosis/*drug therapy/microbiology/pathology ; Zinc/*deficiency ; }, abstract = {Bacteria respond to zinc starvation by replacing ribosomal proteins that have the zinc-binding CXXC motif (C+) with their zinc-free (C-) paralogues. Consequences of this process beyond zinc homeostasis are unknown. Here, we show that the C- ribosome in Mycobacterium smegmatis is the exclusive target of a bacterial protein Y homolog, referred to as mycobacterial-specific protein Y (MPY), which binds to the decoding region of the 30S subunit, thereby inactivating the ribosome. MPY binding is dependent on another mycobacterial protein, MPY recruitment factor (MRF), which is induced on zinc depletion, and interacts with C- ribosomes. MPY binding confers structural stability to C- ribosomes, promoting survival of growth-arrested cells under zinc-limiting conditions. Binding of MPY also has direct influence on the dynamics of aminoglycoside-binding pockets of the C- ribosome to inhibit binding of these antibiotics. Together, our data suggest that zinc limitation leads to ribosome hibernation and aminoglycoside resistance in mycobacteria. Furthermore, our observation of the expression of the proteins of C- ribosomes in Mycobacterium tuberculosis in a mouse model of infection suggests that ribosome hibernation could be relevant in our understanding of persistence and drug tolerance of the pathogen encountered during chemotherapy of TB.}, } @article {pmid30038001, year = {2018}, author = {Carrette, LLG and Blum, R and Ma, W and Kelleher, RJ and Lee, JT}, title = {Tsix-Mecp2 female mouse model for Rett syndrome reveals that low-level MECP2 expression extends life and improves neuromotor function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8185-8190}, pmid = {30038001}, issn = {1091-6490}, support = {R01 DA036895/DA/NIDA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Alleles ; Animals ; Behavior, Animal ; Brain/pathology ; *Disease Models, Animal ; Female ; Genes, X-Linked/*genetics ; Heterozygote ; Humans ; Longevity/*genetics ; Male ; Methyl-CpG-Binding Protein 2/*genetics/metabolism ; *Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Mosaicism ; Motor Activity/genetics ; Mutation ; Phenotype ; RNA, Long Noncoding/*genetics/metabolism ; Rett Syndrome/*genetics/mortality/pathology ; X Chromosome Inactivation ; }, abstract = {Rett syndrome (RTT) is a severe neurodevelopmental disorder caused by a mutation in the X-linked methyl-CpG-binding protein 2 (MECP2). There is currently no disease-specific treatment, but MECP2 restoration through reactivation of the inactive X (Xi) has been of considerable interest. Progress toward an Xi-reactivation therapy has been hampered by a lack of suitable female mouse models. Because of cellular mosaicism due to random X-chromosome inactivation (XCI), Mecp2+/- heterozygous females develop only mild RTT. Here, we create an improved female mouse model by introducing a mutation in Tsix, the antisense regulator of XCI allelic choice. Tsix-Mecp2 mice show reduced MECP2 mosaicism and closely phenocopy the severely affected Mecp2-null males. Tsix-Mecp2 females demonstrate shortened lifespan, motor weakness, tremors, and gait disturbance. Intriguingly, they also exhibit repetitive behaviors, as is often seen in human RTT, including excessive grooming and biting that result in self-injury. With a Tsix allelic series, we vary MECP2 levels in brain and demonstrate a direct, but nonlinear correlation between MECP2 levels and phenotypic improvement. As little as 5-10% MECP2 restoration improves neuromotor function and extends lifespan five- to eightfold. Our study thus guides future pharmacological strategies and suggests that partial MECP2 restoration could have disproportionate therapeutic benefit.}, } @article {pmid30038000, year = {2018}, author = {Lochy, A and Jacques, C and Maillard, L and Colnat-Coulbois, S and Rossion, B and Jonas, J}, title = {Selective visual representation of letters and words in the left ventral occipito-temporal cortex with intracerebral recordings.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7595-E7604}, pmid = {30038000}, issn = {1091-6490}, mesh = {Adult ; Brain Mapping/instrumentation/*methods ; Drug Resistant Epilepsy/diagnosis ; Electrocorticography/instrumentation/*methods ; Electrodes ; Epilepsies, Partial/diagnosis ; Female ; Humans ; Male ; Occipital Lobe/*physiology ; Pattern Recognition, Visual/*physiology ; Reading ; Temporal Lobe/*physiology ; }, abstract = {We report a comprehensive cartography of selective responses to visual letters and words in the human ventral occipito-temporal cortex (VOTC) with direct neural recordings, clarifying key aspects of the neural basis of reading. Intracerebral recordings were performed in a large group of patients (n = 37) presented with visual words inserted periodically in rapid sequences of pseudofonts, nonwords, or pseudowords, enabling classification of responses at three levels of word processing: letter, prelexical, and lexical. While letter-selective responses are found in much of the VOTC, with a higher proportion in left posterior regions, prelexical/lexical responses are confined to the middle and anterior sections of the left fusiform gyrus. This region overlaps with and extends more anteriorly than the visual word form area typically identified with functional magnetic resonance imaging. In this region, prelexical responses provide evidence for populations of neurons sensitive to the statistical regularity of letter combinations independently of lexical responses to familiar words. Despite extensive sampling in anterior ventral temporal regions, there is no hierarchical organization between prelexical and lexical responses in the left fusiform gyrus. Overall, distinct word processing levels depend on neural populations that are spatially intermingled rather than organized according to a strict postero-anterior hierarchy in the left VOTC.}, } @article {pmid30037999, year = {2018}, author = {Alcaino, C and Knutson, KR and Treichel, AJ and Yildiz, G and Strege, PR and Linden, DR and Li, JH and Leiter, AB and Szurszewski, JH and Farrugia, G and Beyder, A}, title = {A population of gut epithelial enterochromaffin cells is mechanosensitive and requires Piezo2 to convert force into serotonin release.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7632-E7641}, pmid = {30037999}, issn = {1091-6490}, support = {R01 DK110614/DK/NIDDK NIH HHS/United States ; R01 DK052766/DK/NIDDK NIH HHS/United States ; P30 DK084567/DK/NIDDK NIH HHS/United States ; R01 DK100223/DK/NIDDK NIH HHS/United States ; K08 DK106456/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Enterochromaffin Cells/*physiology ; Ion Channels/genetics/*metabolism ; Jejunum/cytology/*physiology ; Mechanotransduction, Cellular/*physiology ; Mice ; Mice, Transgenic ; Organoids/physiology ; Primary Cell Culture ; RNA, Small Interfering/metabolism ; Serotonin/*metabolism ; Single-Cell Analysis ; }, abstract = {Enterochromaffin (EC) cells constitute the largest population of intestinal epithelial enteroendocrine (EE) cells. EC cells are proposed to be specialized mechanosensory cells that release serotonin in response to epithelial forces, and thereby regulate intestinal fluid secretion. However, it is unknown whether EE and EC cells are directly mechanosensitive, and if so, what the molecular mechanism of their mechanosensitivity is. Consequently, the role of EE and EC cells in gastrointestinal mechanobiology is unclear. Piezo2 mechanosensitive ion channels are important for some specialized epithelial mechanosensors, and they are expressed in mouse and human EC cells. Here, we use EC and EE cell lineage tracing in multiple mouse models to show that Piezo2 is expressed in a subset of murine EE and EC cells, and it is distributed near serotonin vesicles by superresolution microscopy. Mechanical stimulation of a subset of isolated EE cells leads to a rapid inward ionic current, which is diminished by Piezo2 knockdown and channel inhibitors. In these mechanosensitive EE cells force leads to Piezo2-dependent intracellular Ca2+ increase in isolated cells as well as in EE cells within intestinal organoids, and Piezo2-dependent mechanosensitive serotonin release in EC cells. Conditional knockout of intestinal epithelial Piezo2 results in a significant decrease in mechanically stimulated epithelial secretion. This study shows that a subset of primary EE and EC cells is mechanosensitive, uncovers Piezo2 as their primary mechanotransducer, defines the molecular mechanism of their mechanotransduction and mechanosensitive serotonin release, and establishes the role of epithelial Piezo2 mechanosensitive ion channels in regulation of intestinal physiology.}, } @article {pmid30037998, year = {2018}, author = {Paracini, N and Clifton, LA and Skoda, MWA and Lakey, JH}, title = {Liquid crystalline bacterial outer membranes are critical for antibiotic susceptibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7587-E7594}, pmid = {30037998}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/*pharmacology ; Cell Membrane/chemistry/*metabolism ; Cell Membrane Permeability/drug effects/physiology ; *Drug Resistance, Bacterial ; Gram-Negative Bacteria/*physiology ; Lipid Bilayers/chemistry ; Lipopolysaccharides/chemistry/physiology ; Liquid Crystals/chemistry ; Models, Chemical ; Phase Transition ; Phospholipids/chemistry/physiology ; Polymyxin B/*pharmacology ; Spectrum Analysis ; Temperature ; }, abstract = {The outer membrane (OM) of Gram-negative bacteria is a robust, impermeable, asymmetric bilayer of outer lipopolysaccharides (LPSs) and inner phospholipids containing selective pore proteins which confer on it the properties of a molecular sieve. This structure severely limits the variety of antibiotic molecules effective against Gram-negative pathogens and, as antibiotic resistance has increased, so has the need to solve the OM permeability problem. Polymyxin B (PmB) represents those rare antibiotics which act directly on the OM and which offer a distinct starting point for new antibiotic development. Here we investigate PmB's interactions with in vitro OM models and show how the physical state of the lipid matrix of the OM is a critical factor in regulating the interaction with the antimicrobial peptide. Using neutron reflectometry and infrared spectroscopy, we reveal the structural and chemical changes induced by PmB on OM models of increasing complexity. In particular, only a tightly packed model reproduced the temperature-controlled disruption of the asymmetric lipid bilayer by PmB observed in vivo. By measuring the order of outer-leaflet LPS and inner-leaflet phospholipids, we show that PmB insertion is dependent on the phase transition of LPS from the gel to the liquid crystalline state. The demonstration of a lipid phase transition in the physiological temperature range also supports the hypothesis that bacteria grown at different temperatures adapt their LPS structures to maintain a homeoviscous OM.}, } @article {pmid30037997, year = {2018}, author = {Barczak, A and O'Connell, MN and McGinnis, T and Ross, D and Mowery, T and Falchier, A and Lakatos, P}, title = {Top-down, contextual entrainment of neuronal oscillations in the auditory thalamocortical circuit.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7605-E7614}, pmid = {30037997}, issn = {1091-6490}, support = {R01 DC012947/DC/NIDCD NIH HHS/United States ; R01 MH109289/MH/NIMH NIH HHS/United States ; }, mesh = {Acoustic Stimulation/methods ; Animals ; Auditory Cortex/*physiology ; Auditory Perception/*physiology ; Cues ; Electrocorticography/methods ; Female ; Macaca mulatta/*physiology ; Neural Pathways/physiology ; Neurons/physiology ; Noise ; Pulvinar/*physiology ; }, abstract = {Prior studies have shown that repetitive presentation of acoustic stimuli results in an alignment of ongoing neuronal oscillations to the sequence rhythm via oscillatory entrainment by external cues. Our study aimed to explore the neural correlates of the perceptual parsing and grouping of complex repeating auditory patterns that occur based solely on statistical regularities, or context. Human psychophysical studies suggest that the recognition of novel auditory patterns amid a continuous auditory stimulus sequence occurs automatically halfway through the first repetition. We hypothesized that once repeating patterns were detected by the brain, internal rhythms would become entrained, demarcating the temporal structure of these repetitions despite lacking external cues defining pattern on- or offsets. To examine the neural correlates of pattern perception, neuroelectric activity of primary auditory cortex (A1) and thalamic nuclei was recorded while nonhuman primates passively listened to streams of rapidly presented pure tones and bandpass noise bursts. At arbitrary intervals, random acoustic patterns composed of 11 stimuli were repeated five times without any perturbance of the constant stimulus flow. We found significant delta entrainment by these patterns in the A1, medial geniculate body, and medial pulvinar. In A1 and pulvinar, we observed a statistically significant, pattern structure-aligned modulation of neuronal firing that occurred earliest in the pulvinar, supporting the idea that grouping and detecting complex auditory patterns is a top-down, context-driven process. Besides electrophysiological measures, a pattern-related modulation of pupil diameter verified that, like humans, nonhuman primates consciously detect complex repetitive patterns that lack physical boundaries.}, } @article {pmid30037996, year = {2018}, author = {Sima, J and Yan, Z and Chen, Y and Lehrmann, E and Zhang, Y and Nagaraja, R and Wang, W and Wang, Z and Schlessinger, D}, title = {Eda-activated RelB recruits an SWI/SNF (BAF) chromatin-remodeling complex and initiates gene transcription in skin appendage formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8173-8178}, pmid = {30037996}, issn = {1091-6490}, support = {R01 HL109054/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/*physiology ; Ectodysplasins/genetics/*metabolism ; Edar Receptor/genetics/metabolism ; Female ; Gene Expression Profiling ; HEK293 Cells ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; NF-kappa B/metabolism ; Organogenesis/*genetics ; Proteins/genetics/metabolism ; RNA, Small Interfering/metabolism ; Signal Transduction/physiology ; Skin/*embryology ; Transcription Factor RelB/*genetics/metabolism ; Transcription Factors/*physiology ; Transcription, Genetic/*physiology ; Transcriptional Activation/physiology ; Up-Regulation ; }, abstract = {Ectodysplasin A (Eda) signaling activates NF-κB during skin appendage formation, but how Eda controls specific gene transcription remains unclear. Here, we find that Eda triggers the formation of an NF-κB-associated SWI/SNF (BAF) complex in which p50/RelB recruits a linker protein, Tfg, that interacts with BAF45d in the BAF complex. We further reveal that Tfg is initially induced by Eda-mediated RelB activation and then bridges RelB and BAF for subsequent gene regulation. The BAF component BAF250a is particularly up-regulated in skin appendages, and epidermal knockout of BAF250a impairs skin appendage development, resulting in phenotypes similar to those of Eda-deficient mouse models. Transcription profiling identifies several target genes regulated by Eda, RelB, and BAF. Notably, RelB and the BAF complex are indispensable for transcription of Eda target genes, and both BAF complex and Eda signaling are required to open chromatin of Eda targets. Our studies thus suggest that Eda initiates a signaling cascade and recruits a BAF complex to specific gene loci to facilitate transcription during organogenesis.}, } @article {pmid30037995, year = {2018}, author = {Roos, CI and Zedeño, MN and Hollenback, KL and Erlick, MMH}, title = {Indigenous impacts on North American Great Plains fire regimes of the past millennium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8143-8148}, pmid = {30037995}, issn = {1091-6490}, mesh = {Animals ; Bison ; Charcoal ; Climate ; Climate Change/*history ; Droughts ; Ecology ; *Ecosystem ; Fires ; Geographic Mapping ; Geography ; Geologic Sediments/analysis ; Grassland ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Medieval ; Humans ; Montana ; North America ; Population Dynamics ; Radiometric Dating ; Time Factors ; United States ; Wildfires/*history ; }, abstract = {Fire use has played an important role in human evolution and subsequent dispersals across the globe, yet the relative importance of human activity and climate on fire regimes is controversial. This is particularly true for historical fire regimes of the Americas, where indigenous groups used fire for myriad reasons but paleofire records indicate strong climate-fire relationships. In North American grasslands, decadal-scale wet periods facilitated widespread fire activity because of the abundance of fuel promoted by pluvial episodes. In these settings, human impacts on fire regimes are assumed to be independent of climate, thereby diminishing the strength of climate-fire relationships. We used an offsite geoarchaeological approach to link terrestrial records of prairie fire activity with spatially related archaeological features (driveline complexes) used for intensive, communal bison hunting in north-central Montana. Radiocarbon-dated charcoal layers from alluvial and colluvial deposits associated with driveline complexes indicate that peak fire activity over the past millennium occurred coincident with the use of these features (ca. 1100-1650 CE). However, comparison of dated fire deposits with Palmer Drought Severity Index reconstructions reveal strong climate-fire linkages. More than half of all charcoal layers coincide with modest pluvial episodes, suggesting that fire use by indigenous hunters enhanced the effects of climate variability on prairie fire regimes. These results indicate that relatively small, mobile human populations can impact natural fire regimes, even in pyrogeographic settings in which climate exerts strong, top-down controls on fuels.}, } @article {pmid30037994, year = {2018}, author = {Li, M and Wang, Y and Chen, A and Naidu, A and Napier, BS and Li, W and Rodriguez, CL and Crooker, SA and Omenetto, FG}, title = {Flexible magnetic composites for light-controlled actuation and interfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8119-8124}, pmid = {30037994}, issn = {1091-6490}, abstract = {The interaction between light and matter has been long explored, leading to insights based on the modulation and control of electrons and/or photons within a material. An opportunity exists in optomechanics, where the conversion of radiation into material strain and actuation is currently induced at the molecular level in liquid crystal systems, or at the microelectromechanical systems (MEMS) device scale, producing limited potential strain energy (or force) in light-driven systems. We present here flexible material composites that, when illuminated, are capable of macroscale motion, through the interplay of optically absorptive elements and low Curie temperature magnetic materials. These composites can be formed into films, sponges, monoliths, and hydrogels, and can be actuated with light at desired locations. Light-actuated elastomeric composites for gripping and releasing, heliotactic motion, light-driven propulsion, and rotation are demonstrated as examples of the versatility of this approach.}, } @article {pmid30037993, year = {2018}, author = {Fuchs, HL and Gerbi, GP and Hunter, EJ and Christman, AJ}, title = {Waves cue distinct behaviors and differentiate transport of congeneric snail larvae from sheltered versus wavy habitats.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7532-E7540}, pmid = {30037993}, issn = {1091-6490}, mesh = {Animals ; Aquatic Organisms/physiology ; Behavior, Animal/*physiology ; *Cues ; Ecosystem ; Larva/*physiology ; Motion ; Oceans and Seas ; Population Dynamics ; Snails/*physiology ; Sound ; Swimming/psychology ; *Water Movements ; }, abstract = {Marine population dynamics often depend on dispersal of larvae with infinitesimal odds of survival, creating selective pressure for larval behaviors that enhance transport to suitable habitats. One intriguing possibility is that larvae navigate using physical signals dominating their natal environments. We tested whether flow-induced larval behaviors vary with adults' physical environments, using congeneric snail larvae from the wavy continental shelf (Tritia trivittata) and from turbulent inlets (Tritia obsoleta). Turbulence and flow rotation (vorticity) induced both species to swim more energetically and descend more frequently. Accelerations, the strongest signal from waves, induced a dramatic response in T. trivittata but almost no response in competent T. obsoleta Early stage T. obsoleta did react to accelerations, ruling out differences in sensory capacities. Larvae likely distinguished turbulent vortices from wave oscillations using statocysts. Statocysts' ability to sense acceleration would also enable detection of low-frequency sound from wind and waves. T. trivittata potentially hear and react to waves that provide a clear signal over the continental shelf, whereas T. obsoleta effectively "go deaf" to wave motions that are weak in inlets. Their contrasting responses to waves would cause these larvae to move in opposite directions in the water columns of their respective adult habitats. Simulations showed that the congeners' transport patterns would diverge over the shelf, potentially reinforcing the separate biogeographic ranges of these otherwise similar species. Responses to turbulence could enhance settlement but are unlikely to aid large-scale navigation, whereas shelf species' responses to waves may aid retention over the shelf via Stokes drift.}, } @article {pmid30037992, year = {2018}, author = {Shah, V and Jaeglé, L and Thornton, JA and Lopez-Hilfiker, FD and Lee, BH and Schroder, JC and Campuzano-Jost, P and Jimenez, JL and Guo, H and Sullivan, AP and Weber, RJ and Green, JR and Fiddler, MN and Bililign, S and Campos, TL and Stell, M and Weinheimer, AJ and Montzka, DD and Brown, SS}, title = {Chemical feedbacks weaken the wintertime response of particulate sulfate and nitrate to emissions reductions over the eastern United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8110-8115}, pmid = {30037992}, issn = {1091-6490}, abstract = {Sulfate ([Formula: see text]) and nitrate ([Formula: see text]) account for half of the fine particulate matter mass over the eastern United States. Their wintertime concentrations have changed little in the past decade despite considerable precursor emissions reductions. The reasons for this have remained unclear because detailed observations to constrain the wintertime gas-particle chemical system have been lacking. We use extensive airborne observations over the eastern United States from the 2015 Wintertime Investigation of Transport, Emissions, and Reactivity (WINTER) campaign; ground-based observations; and the GEOS-Chem chemical transport model to determine the controls on winter [Formula: see text] and [Formula: see text] GEOS-Chem reproduces observed [Formula: see text]-[Formula: see text]-[Formula: see text] particulate concentrations (2.45 μg [Formula: see text]) and composition ([Formula: see text]: 47%; [Formula: see text]: 32%; [Formula: see text]: 21%) during WINTER. Only 18% of [Formula: see text] emissions were regionally oxidized to [Formula: see text] during WINTER, limited by low [H2O2] and [OH]. Relatively acidic fine particulates (pH∼1.3) allow 45% of nitrate to partition to the particle phase. Using GEOS-Chem, we examine the impact of the 58% decrease in winter [Formula: see text] emissions from 2007 to 2015 and find that the H2O2 limitation on [Formula: see text] oxidation weakened, which increased the fraction of [Formula: see text] emissions oxidizing to [Formula: see text] Simultaneously, NOx emissions decreased by 35%, but the modeled [Formula: see text] particle fraction increased as fine particle acidity decreased. These feedbacks resulted in a 40% decrease of modeled [[Formula: see text]] and no change in [[Formula: see text]], as observed. Wintertime [[Formula: see text]] and [[Formula: see text]] are expected to change slowly between 2015 and 2023, unless [Formula: see text] and NOx emissions decrease faster in the future than in the recent past.}, } @article {pmid30037991, year = {2018}, author = {Huang, J and Li, J and Zhou, J and Wang, L and Yang, S and Hurst, LD and Li, WH and Tian, D}, title = {Identifying a large number of high-yield genes in rice by pedigree analysis, whole-genome sequencing, and CRISPR-Cas9 gene knockout.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7559-E7567}, pmid = {30037991}, issn = {1091-6490}, mesh = {Agriculture/*methods ; CRISPR-Cas Systems/genetics ; Gene Knockout Techniques/methods ; Genome, Plant/*physiology ; Oryza/genetics/*physiology ; Pedigree ; Phenotype ; Plants, Genetically Modified/genetics/physiology ; *Quantitative Trait Loci ; *Quantitative Trait, Heritable ; Selection, Genetic/genetics ; Sequence Analysis, DNA/methods ; }, abstract = {Repeated artificial selection of a complex trait facilitates the identification of genes underlying the trait, especially if multiple selected descendant lines are available. Here we developed a pedigree-based approach to identify genes underlying the Green Revolution (GR) phenotype. From a pedigree analysis, we selected 30 cultivars including the "miracle rice" IR8, a GR landmark, its ancestors and descendants, and also other related cultivars for identifying high-yield genes. Through sequencing of these genomes, we identified 28 ancestral chromosomal blocks that were maintained in all the high-yield cultivars under study. In these blocks, we identified six genes of known function, including the GR gene sd1, and 123 loci with genes of unknown function. We randomly selected 57 genes from the 123 loci for knockout or knockdown studies and found that a high proportion of these genes are essential or have phenotypic effects related to rice production. Notably, knockout lines have significant changes in plant height (P < 0.003), a key GR trait, compared with wild-type lines. Some gene knockouts or knockdowns were especially interesting. For example, knockout of Os10g0555100, a putative glucosyltransferase gene, showed both reduced growth and altered panicle architecture. In addition, we found that in some retained chromosome blocks several GR-related genes were clustered, although they have unrelated sequences, suggesting clustering of genes with similar functions. In conclusion, we have identified many high-yield genes in rice. Our method provides a powerful means to identify genes associated with a specific trait.}, } @article {pmid30037990, year = {2018}, author = {Otwinowski, J and McCandlish, DM and Plotkin, JB}, title = {Inferring the shape of global epistasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7550-E7558}, pmid = {30037990}, issn = {1091-6490}, support = {T32 AI055400/AI/NIAID NIH HHS/United States ; }, mesh = {*Epistasis, Genetic ; *Evolution, Molecular ; *Genetic Fitness ; Genotype ; *Models, Genetic ; Models, Statistical ; Mutation ; Nonlinear Dynamics ; Phenotype ; }, abstract = {Genotype-phenotype relationships are notoriously complicated. Idiosyncratic interactions between specific combinations of mutations occur and are difficult to predict. Yet it is increasingly clear that many interactions can be understood in terms of global epistasis. That is, mutations may act additively on some underlying, unobserved trait, and this trait is then transformed via a nonlinear function to the observed phenotype as a result of subsequent biophysical and cellular processes. Here we infer the shape of such global epistasis in three proteins, based on published high-throughput mutagenesis data. To do so, we develop a maximum-likelihood inference procedure using a flexible family of monotonic nonlinear functions spanned by an I-spline basis. Our analysis uncovers dramatic nonlinearities in all three proteins; in some proteins a model with global epistasis accounts for virtually all of the measured variation, whereas in others we find substantial local epistasis as well. This method allows us to test hypotheses about the form of global epistasis and to distinguish variance components attributable to global epistasis, local epistasis, and measurement error.}, } @article {pmid30037989, year = {2018}, author = {Lenc, T and Keller, PE and Varlet, M and Nozaradan, S}, title = {Neural tracking of the musical beat is enhanced by low-frequency sounds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8221-8226}, pmid = {30037989}, issn = {1091-6490}, mesh = {Acoustic Stimulation/*psychology ; Adult ; Attention ; Auditory Perception/*physiology ; Brain/*physiology ; Electroencephalography ; Female ; Healthy Volunteers ; Humans ; Male ; Motor Activity/*physiology ; Music/*psychology ; Periodicity ; Sound ; Young Adult ; }, abstract = {Music makes us move, and using bass instruments to build the rhythmic foundations of music is especially effective at inducing people to dance to periodic pulse-like beats. Here, we show that this culturally widespread practice may exploit a neurophysiological mechanism whereby low-frequency sounds shape the neural representations of rhythmic input by boosting selective locking to the beat. Cortical activity was captured using electroencephalography (EEG) while participants listened to a regular rhythm or to a relatively complex syncopated rhythm conveyed either by low tones (130 Hz) or high tones (1236.8 Hz). We found that cortical activity at the frequency of the perceived beat is selectively enhanced compared with other frequencies in the EEG spectrum when rhythms are conveyed by bass sounds. This effect is unlikely to arise from early cochlear processes, as revealed by auditory physiological modeling, and was particularly pronounced for the complex rhythm requiring endogenous generation of the beat. The effect is likewise not attributable to differences in perceived loudness between low and high tones, as a control experiment manipulating sound intensity alone did not yield similar results. Finally, the privileged role of bass sounds is contingent on allocation of attentional resources to the temporal properties of the stimulus, as revealed by a further control experiment examining the role of a behavioral task. Together, our results provide a neurobiological basis for the convention of using bass instruments to carry the rhythmic foundations of music and to drive people to move to the beat.}, } @article {pmid30037988, year = {2018}, author = {Schickinger, M and Zacharias, M and Dietz, H}, title = {Tethered multifluorophore motion reveals equilibrium transition kinetics of single DNA double helices.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7512-E7521}, pmid = {30037988}, issn = {1091-6490}, support = {256270//European Research Council/International ; }, mesh = {Cations/chemistry/metabolism ; DNA/*chemistry/metabolism ; Dimerization ; Fluorescence ; Kinetics ; Nucleic Acid Conformation ; Nucleic Acid Heteroduplexes ; Nucleic Acid Hybridization ; Oligonucleotides/*chemistry/metabolism ; Thermodynamics ; }, abstract = {We describe a tethered multifluorophore motion assay based on DNA origami for revealing bimolecular reaction kinetics on the single-molecule level. Molecular binding partners may be placed at user-defined positions and in user-defined stoichiometry; and binding states are read out by tracking the motion of quickly diffusing fluorescent reporter units. Multiple dyes per reporter unit enable singe-particle observation for more than 1 hour. We applied the system to study in equilibrium reversible hybridization and dissociation of complementary DNA single strands as a function of tether length, cation concentration, and sequence. We observed up to hundreds of hybridization and dissociation events per single reactant pair and could produce cumulative statistics with tens of thousands of binding and unbinding events. Because the binding partners per particle do not exchange, we could also detect subtle heterogeneity from molecule to molecule, which enabled separating data reflecting the actual target strand pair binding kinetics from falsifying influences stemming from chemically truncated oligonucleotides. Our data reflected that mainly DNA strand hybridization, but not strand dissociation, is affected by cation concentration, in agreement with previous results from different assays. We studied 8-bp-long DNA duplexes with virtually identical thermodynamic stability, but different sequences, and observed strongly differing hybridization kinetics. Complementary full-atom molecular-dynamics simulations indicated two opposing sequence-dependent phenomena: helical templating in purine-rich single strands and secondary structures. These two effects can increase or decrease, respectively, the fraction of strand collisions leading to successful nucleation events for duplex formation.}, } @article {pmid30037969, year = {2018}, author = {Ingolia, NT and Hussmann, JA and Weissman, JS}, title = {Ribosome Profiling: Global Views of Translation.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032698}, pmid = {30037969}, issn = {1943-0264}, abstract = {The translation of messenger RNA (mRNA) into protein and the folding of the resulting protein into an active form are prerequisites for virtually every cellular process and represent the single largest investment of energy by cells. Ribosome profiling-based approaches have revolutionized our ability to monitor every step of protein synthesis in vivo, allowing one to measure the rate of protein synthesis across the proteome, annotate the protein coding capacity of genomes, monitor localized protein synthesis, and explore cotranslational folding and targeting. The rich and quantitative nature of ribosome profiling data provides an unprecedented opportunity to explore and model complex cellular processes. New analytical techniques and improved experimental protocols will provide a deeper understanding of the factors controlling translation speed and its impact on protein function and cell physiology as well as the role of ribosomal RNA and mRNA modifications in regulating translation.}, } @article {pmid30037968, year = {2018}, author = {Peer, E and Moshitch-Moshkovitz, S and Rechavi, G and Dominissini, D}, title = {The Epitranscriptome in Translation Regulation.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032623}, pmid = {30037968}, issn = {1943-0264}, abstract = {The cellular proteome reflects the total outcome of many regulatory mechanisms that affect the metabolism of messenger RNA (mRNA) along its pathway from synthesis to degradation. Accumulating evidence in recent years has uncovered the roles of a growing number of mRNA modifications in every step along this pathway, shaping translational output. mRNA modifications affect the translation machinery directly, by influencing translation initiation, elongation and termination, or by altering mRNA levels and subcellular localization. Features of modification-related translational control are described, charting a new and complex layer of translational regulation.}, } @article {pmid30037568, year = {2018}, author = {Mostowy, RJ and Holt, KE}, title = {Diversity-Generating Machines: Genetics of Bacterial Sugar-Coating.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {1008-1021}, pmid = {30037568}, issn = {1878-4380}, abstract = {Bacterial pathogens and commensals are surrounded by diverse surface polysaccharides which include capsules and lipopolysaccharides. These carbohydrates play a vital role in bacterial ecology and interactions with the environment. Here, we review recent rapid advancements in this field, which have improved our understanding of the roles, structures, and genetics of bacterial polysaccharide antigens. Genetic loci encoding the biosynthesis of these antigens may have evolved as bacterial diversity-generating machines, driven by selection from a variety of forces, including host immunity, bacteriophages, and cell-cell interactions. We argue that the high adaptive potential of polysaccharide antigens should be taken into account in the design of polysaccharide-targeting medical interventions like conjugate vaccines and phage-based therapies.}, } @article {pmid30037334, year = {2018}, author = {Musuka, G and Teveredzi, V and Busang, L and Chingombe, I and Makadzange, P and Mokgweetsinyana, S and Ncube, R and Maradzika, J and Chinamasa, CF and Moeti, T}, title = {Community attitudes on tuberculosis in Botswana: an opportunity for improving the National Tuberculosis Programme outcomes, 2011.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {499}, doi = {10.1186/s13104-018-3585-1}, pmid = {30037334}, issn = {1756-0500}, mesh = {Botswana ; Family ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Social Stigma ; *Tuberculosis/etiology/transmission ; }, abstract = {OBJECTIVES: The Botswana tuberculosis HIV Knowledge Attitude and Practice study sought to assess knowledge, attitudes and practices of communities on TB and identify sources of their information on this disease and HIV. Specific objectives of the study were to: (a) collect baseline information on the knowledge, attitudes, and practices about tuberculosis treatment seeking and adherence behaviors in Botswana. (b) Identify barriers which discourage people who may have smear positive tuberculosis from testing and getting treatment (e.g. social stigma) and constraints which prevent them from initiating and completing treatment.

RESULTS: Approximately 92% of respondents (n = 2029), reported that having TB was not something embarrassing, while about 97% (n = 2030) were not ashamed of having a family member with TB. Approximately 95% (n = 2030) expressed willingness to accommodate their relatives with TB at their homes or, work with TB patients (n = 2026). About 21% of the respondents however, believed in myths that TB infection is a result of either having sex with women who had miscarried (n = 2028), or food poisoning (n = 2031) while about 17% believed that TB infection is a result of sleeping with a widow or widower (n = 2031).}, } @article {pmid30036705, year = {2018}, author = {Kriss, M and Hazleton, KZ and Nusbacher, NM and Martin, CG and Lozupone, CA}, title = {Low diversity gut microbiota dysbiosis: drivers, functional implications and recovery.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {34-40}, doi = {10.1016/j.mib.2018.07.003}, pmid = {30036705}, issn = {1879-0364}, abstract = {Dysbiosis, an imbalance in microbial communities, is linked with disease when this imbalance disturbs microbiota functions essential for maintaining health or introduces processes that promote disease. Dysbiosis in disease is predicted when microbiota differ compositionally from a healthy control population, but only truly defined when these differences are mechanistically related to adverse phenotypes. For the human gut microbiota, dysbiosis varies across diseases. One common manifestation is replacement of the complex community of anaerobes typical of the healthy adult gut microbiome with a community of lower overall microbial diversity and increased facultative anaerobes. Here we review diseases in which low-diversity dysbiosis has been observed and mechanistically linked with disease, with a particular focus on liver disease, inflammatory bowel disease, and Clostridium difficile infection.}, } @article {pmid30036701, year = {2018}, author = {Castellanos-Morales, G and Paredes-Torres, LM and Gámez, N and Hernández-Rosales, HS and Sánchez-de la Vega, G and Barrera-Redondo, J and Aguirre-Planter, E and Vázquez-Lobo, A and Montes-Hernández, S and Lira-Saade, R and Eguiarte, LE}, title = {Historical biogeography and phylogeny of Cucurbita: Insights from ancestral area reconstruction and niche evolution.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {38-54}, doi = {10.1016/j.ympev.2018.07.016}, pmid = {30036701}, issn = {1095-9513}, abstract = {Knowledge of the role of geographical and ecological events associated to the divergence process of wild progenitors is important to understand the process of domestication. We analysed the temporal, spatial and ecological patterns of the diversification of Cucurbita, an American genus of worldwide economic importance. We conducted a phylogenetic analysis based on six chloroplast regions (5907 bp) to estimate diversification rates and dates of divergence between taxa. This is the first phylogenetic study to include C. radicans, a wild species that is endemic to the Trans Mexican Volcanic Belt. We performed analysis of ancestral area reconstruction and paleoreconstructions of species distribution models to understand shifts in wild species ranges. We used principal component analysis (PCA) and multivariate analysis of variance (MANOVA) to evaluate the environmental differentiation among taxa within each clade. The phylogenetic analyses showed good support for at least six independent domestication events in Cucurbita. The genus Cucurbita showed a time of divergence of 11.24 Ma (6.88-17 Ma 95% HDP), and the dates of divergence between taxa within each group ranged from 0.35 to 6.58 Ma, being the divergence between C. lundelliana and C. okeechobeensis subsp. martinezii the most recent. The diversification rate of the genus was constant through time. The diversification of most wild taxa occurred during the Pleistocene, and its date of divergence is concordant with the dates of divergence reported for specialized bees of the genera Xenoglossa and Peponapis, suggesting a process of coevolution between Cucurbita and their main pollinators that should be further investigated. Tests of environmental differentiation together with ancestral area reconstruction and species distribution models past projections suggest that divergence was promoted by the onset of geographic barriers and secondary range contraction and by expansion related to glacial-interglacial cycles.}, } @article {pmid30036700, year = {2018}, author = {Herrando-Moraira, S and , }, title = {Exploring data processing strategies in NGS target enrichment to disentangle radiations in the tribe Cardueae (Compositae).}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {69-87}, doi = {10.1016/j.ympev.2018.07.012}, pmid = {30036700}, issn = {1095-9513}, abstract = {Target enrichment is a cost-effective sequencing technique that holds promise for elucidating evolutionary relationships in fast-evolving lineages. However, potential biases and impact of bioinformatic sequence treatments in phylogenetic inference have not been thoroughly explored yet. Here, we investigate this issue with an ultimate goal to shed light into a highly diversified group of Compositae (Asteraceae) constituted by four main genera: Arctium, Cousinia, Saussurea, and Jurinea. Specifically, we compared sequence data extraction methods implemented in two easy-to-use workflows, PHYLUCE and HybPiper, and assessed the impact of two filtering practices intended to reduce phylogenetic noise. In addition, we compared two phylogenetic inference methods: (1) the concatenation approach, in which all loci were concatenated in a supermatrix; and (2) the coalescence approach, in which gene trees were produced independently and then used to construct a species tree under coalescence assumptions. Here we confirm the usefulness of the set of 1061 COS targets (a nuclear conserved orthology loci set developed for the Compositae) across a variety of taxonomic levels. Intergeneric relationships were completely resolved: there are two sister groups, Arctium-Cousinia and Saussurea-Jurinea, which are in agreement with a morphological hypothesis. Intrageneric relationships among species of Arctium, Cousinia, and Saussurea are also well defined. Conversely, conflicting species relationships remain for Jurinea. Methodological choices significantly affected phylogenies in terms of topology, branch length, and support. Across all analyses, the phylogeny obtained using HybPiper and the strictest scheme of removing fast-evolving sites was estimated as the optimal. Regarding methodological choices, we conclude that: (1) trees obtained under the coalescence approach are topologically more congruent between them than those inferred using the concatenation approach; (2) refining treatments only improved support values under the concatenation approach; and (3) branch support values are maximized when fast-evolving sites are removed in the concatenation approach, and when a higher number of loci is analyzed in the coalescence approach.}, } @article {pmid30036699, year = {2018}, author = {Kuang, T and Tornabene, L and Li, J and Jiang, J and Chakrabarty, P and Sparks, JS and Naylor, GJP and Li, C}, title = {Phylogenomic analysis on the exceptionally diverse fish clade Gobioidei (Actinopterygii: Gobiiformes) and data-filtering based on molecular clocklikeness.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {192-202}, doi = {10.1016/j.ympev.2018.07.018}, pmid = {30036699}, issn = {1095-9513}, abstract = {The use of genome-scale data to infer phylogenetic relationships has gained in popularity in recent years due to the progress made in target-gene capture and sequencing techniques. Data filtering, the approach of excluding data inconsistent with the model from analyses, presumably could alleviate problems caused by systematic errors in phylogenetic inference. Different data filtering criteria, such as those based on evolutionary rate and molecular clocklikeness as well as others have been proposed for selecting useful phylogenetic markers, yet few studies have tested these criteria using phylogenomic data. We developed a novel set of single-copy nuclear coding markers to capture thousands of target genes in gobioid fishes, a species-rich lineages of vertebrates, and tested the effects of data-filtering methods based on substitution rate and molecular clocklikeness while attempting to control for the compounding effects of missing data and variation in locus length. We found that molecular clocklikeness was a better predictor than overall substitution rate for phylogenetic usefulness of molecular markers in our study. In addition, when the 100 best ranked loci for our predictors were concatenated and analyzed using maximum likelihood, or combined in a coalescent-based species-tree analysis, the resulting trees showed a well-resolved topology of Gobioidei that mostly agrees with previous studies. However, trees generated from the 100 least clocklike frequently recovered conflicting, and in some cases clearly erroneous topologies with strong support, thus indicating strong systematic biases in those datasets. Collectively these results suggest that data filtering has the potential improve the performance of phylogenetic inference when using both a concatenation approach as well as methods that rely on input from individual gene trees (i.e. coalescent species-tree approaches), which may be preferred in scenarios where incomplete lineage sorting is likely to be an issue.}, } @article {pmid30036698, year = {2018}, author = {Cornejo, C and Chabanenko, S and Scheidegger, C}, title = {Are species-pairs diverging lineages? A nine-locus analysis uncovers speciation among species-pairs of the Lobaria meridionalis-group (Ascomycota).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {48-59}, doi = {10.1016/j.ympev.2018.07.011}, pmid = {30036698}, issn = {1095-9513}, abstract = {In spite of considerable effort to verify the theory of species-pairs, uncertainty still exists about the relationship between sexually or vegetatively reproducing populations of morphologically indistinguishable, sympatric lichen species. The current paper studies putative species-pairs within the Asian Lobaria meridionalis-group, using a nine-locus and time calibrated species-tree approach. Analyses demonstrate that pairs of sexually or vegetatively reproducing lineages split into highly supported monophyletic clades-confirming molecularly the species-pair concept for the L. meridionalis-group. In the broader context of evolution and speciation dynamics in lichenized fungi, this paper attempts to synthesize molecular findings from the last two decades to promote a more modern perception of the species-pair concept. Taxonomically, eight species were found to currently conform to the L. meridionalis-group, which differentiated during the Pliocene and Pleistocene. The coincidence of paleoclimatic events with estimated dates of divergence support a bioclimatic hypothesis for the evolution of species in the L. meridionalis-group, which also explains their current eco-geographic distribution patterns. Greater recognition for species with a long and independent evolutionary history, which merit high conservation priority, will be especially critical for preserving geographically restricted endemics from Southeast Asia, where habitat loss is driving rapid declines.}, } @article {pmid30034216, year = {2018}, author = {Campos, DA and Pereira, EC and Jardim, R and Cuadrat, RR and Bernardes, JS and Dávila, AM}, title = {Homology Inference Based on a Reconciliation Approach for the Comparative Genomics of Protozoa.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318785138}, pmid = {30034216}, issn = {1176-9343}, abstract = {Protozoa parasites are responsible for several diseases in tropical countries, such as malaria, sleeping sickness, Chagas disease, leishmaniasis, amebiasis, and giardiasis, which together threaten millions of people around the world. In addition, most of the classic parasitic diseases due to protozoa are zoonotic. Understanding the biology of these organisms plays a relevant role in combating these diseases. Using homology inference and comparative genomics, this study targeted 3 protozoan species from different Phyla: Cryptosporidium muris (Apicomplexa), Entamoeba invadens (Amoebozoa), and Trypanosoma grayi (Euglenozoa). In this study, we propose a new approach for the identification of homologs, based on the reconciliation of the results of 2 different homology inference software programs. Our results showed that 46.1% (59/128) of the groups inferred by our reconciliation approach could be validated using this methodology. These validated groups are here called homologous Supergroups and were compared with SUPERFAMILY and Pfam Clans.}, } @article {pmid30033663, year = {2018}, author = {Lopes, LD and Pereira E Silva, MC and Weisberg, AJ and Davis, EW and Yan, Q and Varize, CS and Wu, CF and Chang, JH and Loper, JE and Andreote, FD}, title = {Genome variations between rhizosphere and bulk soil ecotypes of a Pseudomonas koreensis population.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4401-4414}, doi = {10.1111/1462-2920.14363}, pmid = {30033663}, issn = {1462-2920}, support = {302168/2014-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; //Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; 2013/50353-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2011-67019-301922014-51181-22384//National Institute of Food and Agriculture/ ; DGE-1314109//National Science Foundation Graduate Research Fellowship/ ; }, abstract = {Bulk soil and rhizosphere are soil compartments selecting different microbial communities. However, it is unknown whether this selection also can change the genome content of specific bacterial taxa, splitting a population in distinct ecotypes. To answer this question we compared the genome sequences of 53 isolates obtained from sugarcane rhizosphere (28) and bulk soil (25). These isolates were previously classified in the Pseudomonas koreensis subgroup of the P. fluorescens complex. Phylogenomics showed a trend of separation between bulk soil and rhizosphere isolates. Discriminant analysis of principal components (DAPC) identified differences in the accessory genome of rhizosphere and bulk soil sub-populations. We found significant changes in gene frequencies distinguishing rhizosphere from bulk soil ecotypes, for example, enrichment of phosphatases and xylose utilization (xut) genes, respectively. Phenotypic assays and deletion of xutA gene indicated that accumulation of xut genes in the bulk soil sub-population provided a higher growth capacity in a d-xylose medium, supporting the corresponding genomic differences. Despite the clear differences distinguishing the two ecotypes, all 53 isolates were classified in a single 16S rRNA gene OTU. Collectively, our results revealed that the gene pool and ecological behavior of a bacterial population can be different for ecotypes living in neighbouring soil habitats.}, } @article {pmid30033661, year = {2018}, author = {García-Romero, I and Förstner, KU and Santero, E and Floriano, B}, title = {SuhB, a small non-coding RNA involved in catabolite repression of tetralin degradation genes in Sphingopyxis granuli strain TFA.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3671-3683}, doi = {10.1111/1462-2920.14360}, pmid = {30033661}, issn = {1462-2920}, support = {BIO201457545R//Ministry of Economy and Competitiveness/ ; BIO201124003//Ministry of Economy and Competitiveness/ ; }, abstract = {Global dRNA-seq analysis of transcription start sites combined with in silico annotation using Infernal software revealed the expression of 91 putative non-coding sRNA in Sphingopyxis granuli TFA cells grown on different carbon sources. Excluding housekeeping sRNAs, only one additional sRNA, which belongs to the Rfam SuhB family (RF00519), was detected by Infernal but with an incorrect size according to the experimental results. SuhB is highly conserved across the Sphingopyxis genus. Expression data revealed that SuhB is present in rapidly growing TFA cells. A suhB deletion mutant exhibited de-repression of tetralin degradation (thn) gene expression and higher amounts of their LysR-type activator, ThnR, under conditions of carbon catabolite repression (CCR). Interaction between SuhB and the 5'UTR of thnR mRNA was demonstrated in vitro. Moreover, co-immunoprecipitation experiments, combined with fluorescence measurements of gfp fusions to the 5'UTR of thnR mRNA and the phenotype of an hfq deletion mutant, suggest the involvement of Hfq in this interaction. Taken together, these data support an Hfq-mediated repressive role for SuhB, on ThnR mRNA translation that prevents thn gene induction. SuhB, which is a highly conserved sRNA in the Sphingopyxis genus, is the first identified element directly involved in CCR of thn gene expression in S. granuli strain TFA.}, } @article {pmid30033343, year = {2019}, author = {Walsh, D and Naghavi, MH}, title = {Exploitation of Cytoskeletal Networks during Early Viral Infection.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {39-50}, doi = {10.1016/j.tim.2018.06.008}, pmid = {30033343}, issn = {1878-4380}, support = {P01 GM105536/GM/NIGMS NIH HHS/United States ; R01 GM101975/GM/NIGMS NIH HHS/United States ; }, abstract = {Being dependent upon host transport systems to navigate the cytoplasm, viruses have evolved various strategies to manipulate cytoskeletal functions. Generally, viruses use the actin cytoskeleton to control entry and short-range transport at the cell periphery and exploit microtubules (MTs) for longer-range cytosolic transport, in some cases to reach the nucleus. While earlier studies established the fundamental importance of these networks to successful infection, the mechanistic details and true extent to which viruses usurp highly specialized host cytoskeletal regulators and motor adaptors is only beginning to emerge. This review outlines our current understanding of how cytoskeletal regulation contributes specifically to the early stages of viral infection, with a primary focus on retroviruses and herpesviruses as examples of recent advances in this area.}, } @article {pmid30032303, year = {2018}, author = {Abdelkrim, J and Aznar-Cormano, L and Fedosov, AE and Kantor, YI and Lozouet, P and Phuong, MA and Zaharias, P and Puillandre, N}, title = {Exon-Capture-Based Phylogeny and Diversification of the Venomous Gastropods (Neogastropoda, Conoidea).}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2355-2374}, doi = {10.1093/molbev/msy144}, pmid = {30032303}, issn = {1537-1719}, abstract = {Transcriptome-based exon capture methods provide an approach to recover several hundred markers from genomic DNA, allowing for robust phylogenetic estimation at deep timescales. We applied this method to a highly diverse group of venomous marine snails, Conoidea, for which published phylogenetic trees remain mostly unresolved for the deeper nodes. We targeted 850 protein coding genes (678,322 bp) in ca. 120 samples, spanning all (except one) known families of Conoidea and a broad selection of non-Conoidea neogastropods. The capture was successful for most samples, although capture efficiency decreased when DNA libraries were of insufficient quality and/or quantity (dried samples or low starting DNA concentration) and when targeting the most divergent lineages. An average of 75.4% of proteins was recovered, and the resulting tree, reconstructed using both supermatrix (IQ-tree) and supertree (Astral-II, combined with the Weighted Statistical Binning method) approaches, are almost fully supported. A reconstructed fossil-calibrated tree dates the origin of Conoidea to the Lower Cretaceous. We provide descriptions for two new families. The phylogeny revealed in this study provides a robust framework to reinterpret changes in Conoidea anatomy through time. Finally, we used the phylogeny to test the impact of the venom gland and radular type on diversification rates. Our analyses revealed that repeated losses of the venom gland had no effect on diversification rates, while families with a breadth of radula types showed increases in diversification rates, thus suggesting that trophic ecology may have an impact on the evolution of Conoidea.}, } @article {pmid30032189, year = {2018}, author = {Donhauser, J and Frey, B}, title = {Alpine soil microbial ecology in a changing world.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy099}, pmid = {30032189}, issn = {1574-6941}, abstract = {Climate change has a disproportionally large impact on alpine soil ecosystems, leading to pronounced changes in soil microbial diversity and function associated with effects on biogeochemical processes at the local and supraregional scales. However, due to restricted accessibility, high-altitude soils remain largely understudied and a considerable heterogeneity hampers the comparability of different alpine studies. Here, we highlight differences and similarities between alpine and arctic ecosystems, and we discuss the impact of climatic variables and associated vegetation and soil properties on microbial ecology. We consider how microbial alpha-diversity, community structures and function change along altitudinal gradients and with other topographic features such as slope aspect. In addition, we focus on alpine permafrost soils, harboring a surprisingly large unknown microbial diversity and on microbial succession along glacier forefield chronosequences constituting the most thoroughly studied alpine habitat. Finally, highlighting experimental approaches, we present climate change studies showing shifts in microbial community structures and function in response to warming and altered moisture, interestingly with some contradiction. Collectively, despite harsh environmental conditions, many specially adapted microorganisms are able to thrive in alpine environments. Their community structures strongly correlate with climatic, vegetation and soil properties and thus closely mirror the complexity and small-scale heterogeneity of alpine soils.}, } @article {pmid30032139, year = {2018}, author = {Mazen, I and McElreavey, K and Eid, MM and Bashamboo, A and Kamah, G}, title = {A Homozygous Missense Mutation in FANCA Gene in a 46,XY Female with Gonadal Dysgenesis.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000491407}, pmid = {30032139}, issn = {1661-5433}, abstract = {Fanconi anemia (FA) is a pleiotropic condition with 2 characteristic phenotypic markers of hematological and cytogenetic changes. The phenotype of patients with FA is very heterogeneous, associated with an array of congenital malformations affecting the skeletal, renal, genital, and/or central nervous systems. Here, we report on a 46,XY female who presented with gonadal dysgenesis and microcephaly. Exome sequencing showed that she was homozygous for a rare variant in the FANCA gene (c.4232C>T, p.P1411L, rs201494304). Both parents were heterozygous for the mutation. The FA mutation was associated with an atypical clinical presentation, and thus exome sequencing provided essential data that otherwise would have been overlooked in the diagnosis of this patient.}, } @article {pmid30031896, year = {2018}, author = {Khaleque, HN and Shafique, R and Kaksonen, AH and Boxall, NJ and Watkin, ELJ}, title = {Quantitative proteomics using SWATH-MS identifies mechanisms of chloride tolerance in the halophilic acidophile Acidihalobacter prosperus DSM 14174.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {638-648}, doi = {10.1016/j.resmic.2018.07.002}, pmid = {30031896}, issn = {1769-7123}, mesh = {Acids/*metabolism ; Bacterial Proteins/chemistry/*genetics/metabolism ; Chlorides/*metabolism ; DNA Repair ; Gammaproteobacteria/chemistry/genetics/*metabolism ; Mass Spectrometry ; Proteomics ; Sodium Chloride/*metabolism ; }, abstract = {In this study, the differential protein expression of the acidophilic halophile, Acidihalobacter prosperus DSM 14174 (strain V6) was studied with the aim of understanding its mechanisms of tolerance to high chloride ion stress in the presence of low pH, using Sequential Window Acquisition of all Theoretical Mass Spectra (SWATH-MS). In acidophiles, chloride stress results in both osmotic stress as well as acidification of the cytoplasm due to the ability of chloride to permeate the cell membrane and disrupt the reversed transmembrane potential which normally extrudes protons. The proteomic response of A. prosperus DSM 14174 to elevated chloride concentrations included the production of osmotic stress regulators that potentially induced the production of compatibles solutes, of which the most significant increase was in the synthesis of ectoine. Other responses directly related to the increased chloride and acid stress, included the increased synthesis of glutathione, changes in carbon flux, the increased production of amino acids, the decreased production of ribosomal proteins, the efflux of metals and protons, and the increase in proteins involved in DNA repair and membrane biosynthesis. Energy generation through iron oxidation and sulphur oxidation were decreased, and energy was probably obtained from the metabolism of glycogen stores. Overall, these studies have helped to create a model of tolerance to elevated chloride under acidic conditions by A. prosperus DSM 14174 that differs from the previous model developed for the type strain, A. prosperus DSM 5130T.}, } @article {pmid30031771, year = {2018}, author = {Wade, RM and Sherwood, AR}, title = {Updating Plakobranchus cf. ianthobapsus (Gastropoda, Sacoglossa) host use: Diverse algal-animal interactions revealed by NGS with implications for invasive species management.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {172-181}, doi = {10.1016/j.ympev.2018.07.010}, pmid = {30031771}, issn = {1095-9513}, abstract = {Sacoglossa, the "sap sucking" sea slugs, are highly specialized herbivores and the only metazoans that exhibit kleptoplasty, the sequestration and retention of chloroplasts from algae. Plakobranchus is one of the most generalistic herbivores within this order, with as many as 12 reported "algal host" (i.e. kleptoplast source) species. However, kleptoplast diversity studies conducted on Plakobranchus to date most likely underestimated the full diversity of kleptoplast sources within the studied populations due to limitations of the molecular techniques employed. Here, we apply a high throughput sequencing technique to assess kleptoplast diversity of Plakobranchus cf. ianthobapsus' from 10 sites across the Main Hawaiian Islands during winter and summer seasons. In so doing, we effectively used P. cf. ianthobapsus as a novel sampling tool to explore diminutive algal communities, including the current distribution of the invasive alga "Avrainvillea amadelpha." Our results show that P. cf. ianthobapsus sequesters chloroplasts from 23 algal species from across the siphonous green algal order Bryopsidales. We identified "Avrainvillea amadelpha" and Codium edule as new host species for P. cf. ianthobapusus, but their rarity among the data suggests they were most likely less preferential as hosts and were possibly utilized due to low abundance or unavailability of more preferable species, and therefore a response to starvation risk. Additionally, the identification of the highly invasive siphonous green alga "A. amadelpha" as a kleptoplast source provides new fine-scale range and distribution data for this problematic species. Overall kleptoplast diversity does not differ among sites, except in a coral-dominated, (i.e. not algal dominated) environment, suggesting that siphonous algal assemblages are common in algal-dominated ecosystems in the Hawaiian Islands. Diversity dissimilarity among seasons was recovered from the majority of sites sampled, supporting the need for seasonal data collection in algal diversity assessments. This case study using metabarcoding of sacoglossan kleptoplasts provides deeper insights into these plant-animal interactions with a better understanding of host use than previous studies using traditional molecular methods and illustrates how algal diversity studies on the scale of plastids can have implications for understanding algal community structure and invasive species dynamics.}, } @article {pmid30031757, year = {2018}, author = {Espinasa, L and Robinson, J and Espinasa, M}, title = {Mc1r gene in Astroblepus pholeter and Astyanax mexicanus: Convergent regressive evolution of pigmentation across cavefish species.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {305-310}, doi = {10.1016/j.ydbio.2018.07.016}, pmid = {30031757}, issn = {1095-564X}, mesh = {*5' Untranslated Regions ; Animals ; Catfishes/*genetics/metabolism ; Characiformes/*genetics/metabolism ; *Evolution, Molecular ; Melatonin/*genetics/metabolism ; *Mutation ; }, abstract = {Cave-adapted organisms are often characterized by a reduction in pigmentation, eyesight, and enhanced mechanosensory functions. Previous studies have described the genetic basis for a depigmented phenotype in multiple independent populations of the Blind Mexican Tetra, Astyanax mexicanus; the reduction in melanin content (brown; Mc1r). At least seven wild populations express the brown phenotype. In three populations, there are two different coding sequence alterations affecting Mc1r and the remaining four populations show the accumulation of sequence mutations affecting the 5' regulatory region. Thus, the Mc1r gene has been the repeated and independent location of mutations in Astyanax. As such, it would appear that this gene is a target during regressive evolution of cave adapted organisms. If this is the case, it would be expected that other cave adapted fish would have mutations in the same gene. We study here the stygobitic catfish Astroblepus pholeter, a depigmented fish found within some river caves in Ecuador. A. pholeter displays mutations in ultra-conserved areas of the pigment-controlling gene, Mc1r, that have been linked to pigment regulation in other organisms. It is thus concluded that Mc1r, a gene known to control pigment variation in many organisms, may be the target of cavernicole regressive evolution across species in different families of fish.}, } @article {pmid30031756, year = {2018}, author = {Eusebio, N and Tavares, L and Pereira, PS}, title = {CtBP represses Dpp-dependent Mad activation during Drosophila eye development.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {188-198}, doi = {10.1016/j.ydbio.2018.07.018}, pmid = {30031756}, issn = {1095-564X}, mesh = {Activin Receptors, Type II/genetics/metabolism/*physiology ; Alcohol Oxidoreductases/metabolism/*physiology ; Animals ; Cell Differentiation/genetics ; Cyclin-Dependent Kinase 4 ; DNA-Binding Proteins/*metabolism/*physiology ; Drosophila Proteins/genetics/*metabolism/*physiology ; Drosophila melanogaster/genetics/metabolism ; Eye/embryology/metabolism ; Gene Expression Regulation, Developmental/genetics ; Morphogenesis ; Organogenesis ; Repressor Proteins/metabolism ; Signal Transduction/genetics ; Transcription Factors/*metabolism/physiology ; Transforming Growth Factor beta/metabolism ; }, abstract = {Complex networks of signaling pathways maintain the correct balance between positive and negative growth signals, ensuring that tissues achieve proper sizes and differentiation pattern during development. In Drosophila, Dpp, a member of the TGFβ family, plays two main roles during larval eye development. In the early eye primordium, Dpp promotes growth and cell survival, but later on, it switches its function to induce a developmentally-regulated cell cycle arrest in the G1 phase and neuronal photoreceptor differentiation. To advance in the identification and characterization of regulators and targets of Dpp signaling required for retinal development, we carried out an in vivo eye-targeted double-RNAi screen to identify punt (Type II TGFβ receptor) interactors. Using a set of 251 genes associated with eye development, we identified CtBP, Dad, Ago and Brk as punt genetic interactors. Here, we show that downregulation of Ago, or conditions causing increased tissue growth including overexpression of Myc or CyclinD-Cdk4 are sufficient to partially rescue punt-dependent growth and photoreceptor differentiation. Interestingly, we show a novel role for the transcriptional co-repressor CtBP in inhibiting Dpp-dependent Mad activation by phosphorylation, downstream or in parallel to Dad, the inhibitory Smad. Furthermore, CtBP downregulation activates JNK signaling pathway, implying a complex regulation of signaling pathways by CtBP during eye development.}, } @article {pmid30031755, year = {2018}, author = {Ren, X and Hamilton, N and Müller, F and Yamamoto, Y}, title = {Cellular rearrangement of the prechordal plate contributes to eye degeneration in the cavefish.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {221-234}, doi = {10.1016/j.ydbio.2018.07.017}, pmid = {30031755}, issn = {1095-564X}, support = {PG/12/39/29626//British Heart Foundation/United Kingdom ; BB/C517041/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Characiformes/embryology/genetics ; Eye/*embryology ; *Eye Abnormalities/embryology/genetics ; *Fish Proteins/biosynthesis/genetics ; Gastrula/embryology ; Signal Transduction/*genetics ; }, abstract = {Astyanax mexicanus consists of two different populations: a sighted surface-dwelling form (surface fish) and a blind cave-dwelling form (cavefish). In the cavefish, embryonic expression of sonic hedgehog a (shha) in the prechordal plate is expanded towards the anterior midline, which has been shown to contribute to cavefish specific traits such as eye degeneration, enhanced feeding apparatus, and specialized brain anatomy. However, it is not clear how this expanded expression is achieved and which signaling pathways are involved. Nodal signaling has a crucial role for expression of shh and formation of the prechordal plate. In this study, we report increased expression of prechordal plate marker genes, nodal-related 2 (ndr2) and goosecoid (gsc) in cavefish embryos at the tailbud stage. To investigate whether Nodal signaling is responsible for the anterior expansion of the prechordal plate, we used an inhibitor of Nodal signaling and showed a decreased anterior expansion of the prechordal plate and increased pax6 expression in the anterior midline in treated cavefish embryos. Later in development, the lens and optic cup of treated embryos were significantly larger than untreated embryos. Conversely, increasing Nodal signaling in the surface fish embryo resulted in the expansion of anterior prechordal plate and reduction of pax6 expression in the anterior neural plate together with the formation of small lenses and optic cups later in development. These results confirmed that Nodal signaling has a crucial role for the anterior expansion of the prechordal plate and plays a significant role in cavefish eye development. We showed that the anterior expansion of the prechordal plate was not due to increased total cell number, suggesting the expansion is achieved by changes in cellular distribution in the prechordal plate. In addition, the distribution of presumptive prechordal plate cells in Spemann's organiser was also altered in the cavefish. These results suggested that changes in the cellular arrangement of Spemann's organiser in early gastrulae could have an essential role in the anterior expansion of the prechordal plate contributing to eye degeneration in the cavefish.}, } @article {pmid30031754, year = {2018}, author = {Ma, L and Strickler, AG and Parkhurst, A and Yoshizawa, M and Shi, J and Jeffery, WR}, title = {Maternal genetic effects in Astyanax cavefish development.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {209-220}, pmid = {30031754}, issn = {1095-564X}, support = {R01 EY024941/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/genetics ; *Characiformes/embryology/genetics ; *Crosses, Genetic ; Eye/*embryology ; Female ; *Fish Proteins/biosynthesis/genetics ; Gene Expression Regulation, Developmental/*physiology ; Male ; Maternal Inheritance/*physiology ; }, abstract = {The role of maternal factors in the evolution of development is poorly understood. Here we describe the use of reciprocal hybridization between the surface dwelling (surface fish, SF) and cave dwelling (cavefish, CF) morphs of the teleost Astyanax mexicanus to investigate the roles of maternal genetic effects in cavefish development. Reciprocal hybridization, a procedure in which F1 hybrids are generated by fertilizing SF eggs with CF sperm (SF × CF hybrids) and CF eggs with SF sperm (CF × SF hybrids), revealed that the CF degenerative eye phenotype showed maternal genetic effects. The eyes of CF × SF hybrids resembled the degenerate eyes of CF in showing ventral reduction of the retina and corresponding displacement of the lens within the optic cup, a smaller lens and eyeball, more lens apoptosis, a smaller cartilaginous sclera, and lens-specific gene expression characteristics compared to SF × CF hybrids, which showed eye and lens gene expression phenotypes resembling SF. In contrast, reciprocal hybridization failed to support roles for maternal genetic effects in the CF regressive pigmentation phenotype or in CF constructive changes related to enhanced jaw development. Maternal transcripts encoded by the pou2f1b, runx2b, and axin1 genes, which are involved in determining ventral embryonic fates, were increased in unfertilized CF eggs. In contrast, maternal mRNAs encoded by the ß-catenin and syntabulin genes, which control dorsal embryonic fates, showed similar expression levels in unfertilized SF and CF eggs. Furthermore, maternal transcripts of a sonic hedgehog gene were detected in SF and CF eggs and early cleaving embryos. This study reveals that CF eye degeneration is controlled by changes in maternal factors produced during oogenesis and introduces A. mexicanus as a model system for studying the role of maternal changes in the evolution of development.}, } @article {pmid30031590, year = {2019}, author = {Foster, TJ}, title = {Can β-Lactam Antibiotics Be Resurrected to Combat MRSA?.}, journal = {Trends in microbiology}, volume = {27}, number = {1}, pages = {26-38}, doi = {10.1016/j.tim.2018.06.005}, pmid = {30031590}, issn = {1878-4380}, abstract = {The use of β-lactam antibiotics to treat infections caused by Staphylococcus aureus has been severely compromised by the acquisition by horizontal gene transfer of a gene that encodes the β-lactam-insensitive penicillin-binding protein PBP2a. This allows methicillin-resistant S. aureus (MRSA) to proliferate in the presence of β-lactam antibiotics. Paradoxically the dependence on PBP2a for the essential transpeptidase activity in cell wall peptidoglycan biosynthesis is the 'Achilles heel' of MRSA. Compounds that disrupt the divisome, wall teichoic acid, and functional membrane microdomains act synergistically with β-lactams against MRSA. These include drugs such as statins that are widely used in human medicine. The antibiotics vancomycin and daptomycin are also synergistic with β-lactams, and combinations have been employed to treat persistent MRSA infections. An additional benefit of exposing MRSA to β-lactams could be a reduction in virulence mediated by interfering with the global regulator Agr. The mechanistic basis of synergy is discussed, and the possibility that β-lactams can be resurrected to combat MRSA infections is explored.}, } @article {pmid30031562, year = {2018}, author = {Yeung, ACY and Richardson, JS}, title = {Expanding Resilience Comparisons to Address Management Needs: A Response to Ingrisch and Bahn.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {647-649}, doi = {10.1016/j.tree.2018.06.005}, pmid = {30031562}, issn = {1872-8383}, mesh = {*Conservation of Natural Resources ; *Ecosystem ; }, } @article {pmid30031406, year = {2018}, author = {Greenstein, RJ and Su, L and Fam, PS and Stabel, JR and Brown, ST}, title = {Failure to detect M. avium subspecies paratuberculosis in Johne's disease using a proprietary fluorescent in situ hybridization assay.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {498}, pmid = {30031406}, issn = {1756-0500}, mesh = {Animals ; Biological Assay ; Cattle ; Cattle Diseases ; Diagnostic Tests, Routine ; *In Situ Hybridization, Fluorescence ; Mycobacterium avium subsp. paratuberculosis/genetics/*isolation & purification ; Paratuberculosis/*microbiology ; Sequence Analysis, DNA ; }, abstract = {OBJECTIVES: Mycobacterium avium subspecies paratuberculosis (MAP) causes Johne's disease in ruminants. The "gold standard" of MAP detection is by culture, DNA sequencing possibly supplemented by identification of Ziehl-Neelsen positive mycobacteria. The purpose of this study was to evaluate a proprietary (Affymetrix™ RNA view®) fluorescent in situ hybridization (FISH) assay for MAP RNA. Intestine from a steer with documented Johne's disease was assayed according to the manufacturer's instructions. Probes were custom designed for MAP and bovine β-actin (as the eukaryotic housekeeping gene) from published genomes. We attempt to prevent false positive signal in the "no-probe" control, by modifying wash solutions, using recommended hydrochloric acid titration and different fluorescent filters (TritC for Texas Red and "Hope" for Cy-5).

RESULTS: Repetitively, false positive signal was observed in our "no probe" negative control. Attempts to correct this according to the manufacturers suggestions, and with multiple derivative techniques have been unsuccessful. It is concluded that when performed according to manufactures instruction and with multiple variations on the manufactures recommended suggestions to correct for false positive signal, that the Affymetrix™ RNA view® cannot be used to detect MAP in pre-frozen intestine of cattle with Johne's disease.}, } @article {pmid30031405, year = {2018}, author = {Zhang, AN and Li, LG and Ma, L and Gillings, MR and Tiedje, JM and Zhang, T}, title = {Conserved phylogenetic distribution and limited antibiotic resistance of class 1 integrons revealed by assessing the bacterial genome and plasmid collection.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {130}, pmid = {30031405}, issn = {2049-2618}, mesh = {*Drug Resistance, Bacterial ; Evolution, Molecular ; Gammaproteobacteria/drug effects/*genetics ; Gene Transfer, Horizontal ; Genome, Bacterial ; *Integrons ; Phylogeny ; Plasmids/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Integrons, especially the class 1 integrons, are major contributors to the acquisition and dissemination of antibiotic resistance genes (ARGs). However, comprehensive knowledge of the types, content, and distribution of integrons in bacterial taxa is lacking to evaluate their contribution.

RESULTS: We have constructed a new integrase database and developed a pipeline that provides comprehensive recovery of class 1 integrons. Previous PCR-based techniques might only detect one fourth of the integron-integrases and integrons recovered in this study. By exploring the class 1 integrons in over 73,000 currently available complete and draft bacterial genomes, the contribution of class 1 integrons in spreading and acquiring ARGs was evaluated. Firstly, the host species of class 1 integrons are highly conserved within (96%) in class Gammaproteobacteria, dominated by four pathogenic species of "ESKAPE." Secondly, more than half of class 1 integrons are embedded in chromosomes with less potential for horizontal gene transfer. Finally, ARGs that have been acquired by these integrons only cover 11% of all the ARG genotypes detected in bacterial genomes.

CONCLUSIONS: The above observations indicated that there are both biological and ecological limitations to class 1 integrons in acquiring and spreading ARGs across different classes of the domain Bacteria.}, } @article {pmid30031243, year = {2018}, author = {Paul, W and Marta, C and Tom, VW}, title = {Resolving host-microbe interactions in the gut: the promise of in vitro models to complement in vivo research.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {28-33}, doi = {10.1016/j.mib.2018.07.001}, pmid = {30031243}, issn = {1879-0364}, abstract = {While animal models remain essential for inferring causality, they exhibit important limitations, which restrict the direct translation of findings into new approaches aimed at steering host-microbe interactions for the improvement of human health. Different in vitro models have therefore been developed which incorporate human cell types and microbiota. By virtue of their intricate designs, these models result in human and microbial read-outs reflective of in vivo gut physiology, and present important alternatives to animal models. However, to allow systematic investigations of the interactions between gut microbiota and different human cell types and body systems, ever more complex cell assemblies are necessary which will culminate in the establishment of personalized in vitro models. Such models will allow the unravelling of human-microbe interdependencies and will open exciting new avenues for microbiome-tailored nutrition and drug development.}, } @article {pmid30031071, year = {2018}, author = {Falagán, C and Johnson, DB}, title = {The significance of pH in dictating the relative toxicities of chloride and copper to acidophilic bacteria.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {552-557}, doi = {10.1016/j.resmic.2018.07.004}, pmid = {30031071}, issn = {1769-7123}, mesh = {Acidiphilium/drug effects/genetics/growth & development/*metabolism ; Acidithiobacillus/drug effects/genetics/growth & development/*metabolism ; Acids/*metabolism ; Bacteria/*drug effects/genetics/metabolism ; Chlorides/metabolism/*toxicity ; Clostridiales/drug effects/genetics/growth & development/*metabolism ; Copper/metabolism/*toxicity ; Culture Media/chemistry/metabolism ; Hydrogen-Ion Concentration ; }, abstract = {The ability of acidophilic bacteria to grow in the presence of elevated concentrations of cationic transition metals, though varying between species, has long been recognized to be far greater than that of most neutrophiles. Conversely, their sensitivity to both inorganic and organic anions, with the notable exception of sulfate, has generally been considered to be far more pronounced. We have compared the tolerance of different species of mineral-oxidizing Acidithiobacillus and Sulfobacillus, and the heterotrophic iron-reducer Acidiphilium cryptum, to copper and chloride when grown on ferrous iron, hydrogen or glucose as electron donors at pH values between 2.0 and 3.0. While tolerance of copper varied greatly between species, these were invariably far greater at pH 2.0 than at pH 3.0, while their tolerance of chloride showed the opposite pattern. The combination of copper and chloride in liquid media appeared to be far more toxic than when these elements were present alone, which was thought to be due to the formation of copper-chloride complexes. The results of this study bring new insights into the understanding of the physiological behaviour of metal-mobilising acidophilic bacteria, and have generic significance for the prospects of bioleaching copper ores and concentrates in saline and brackish waters.}, } @article {pmid30030982, year = {2018}, author = {Seidel, HS and Smith, TA and Evans, JK and Stamper, JQ and Mast, TG and Kimble, J}, title = {C. elegans germ cells divide and differentiate in a folded tissue.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {173-187}, doi = {10.1016/j.ydbio.2018.07.013}, pmid = {30030982}, issn = {1095-564X}, support = {P40 OD010440/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans/embryology/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Cell Differentiation/physiology ; Cell Division/physiology ; Cell Proliferation ; Female ; Germ Cells/*cytology/*metabolism ; Male ; Stem Cells/cytology ; }, abstract = {Knowing how stem cells and their progeny are positioned within their tissues is essential for understanding their regulation. One paradigm for stem cell regulation is the C. elegans germline, which is maintained by a pool of germline stem cells in the distal gonad, in a region known as the 'progenitor zone'. The C. elegans germline is widely used as a stem cell model, but the cellular architecture of the progenitor zone has been unclear. Here we characterize this architecture by creating virtual 3D models of the progenitor zone in both sexes. We show that the progenitor zone in adult hermaphrodites is organized like a folded epithelium. The progenitor zone in males is not folded. Analysis of germ cell division shows that daughter cells are born side-by-side along the epithelial-like surface of the germline tissue. Analysis of a key regulator driving differentiation, GLD-1, shows that germ cells in hermaphrodites differentiate along a folded path, with previously described "steps" in GLD-1 expression corresponding to germline folds. Our study provides a three-dimensional view of how C. elegans germ cells progress from stem cell to overt differentiation, with critical implications for regulators driving this transition.}, } @article {pmid30030877, year = {2018}, author = {Heldstab, SA and Isler, K and van Schaik, CP}, title = {Hibernation constrains brain size evolution in mammals.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1582-1588}, doi = {10.1111/jeb.13353}, pmid = {30030877}, issn = {1420-9101}, support = {31003A-144210//Swiss National Science Foundation/ ; //A. H. Schultz Foundation/ ; //University of Zurich/ ; }, abstract = {The expensive brain hypothesis predicts that the lowest stable level of steady energy input acts as a strong constraint on a species' brain size, and thus, that periodic troughs in net energy intake should select for reduced brain size relative to body mass. Here, we test this prediction for the extreme case of hibernation. Hibernators drastically reduce food intake for up to several months and are therefore expected to have smaller relative brain sizes than nonhibernating species. Using a comparative phylogenetic approach on brain size estimates of 1104 mammalian species, and controlling for possible confounding variables, we indeed found that the presence of hibernation in mammals is correlated with decreased relative brain size. This result adds to recent comparative work across mammals and amphibians supporting the idea that environmental seasonality (where in extremis hibernation is necessary for survival) imposes an energetic challenge and thus acts as an evolutionary constraint on relative brain size.}, } @article {pmid30030563, year = {2018}, author = {Wang, Y and Li, B and Dong, H and Huang, X and Chen, R and Chen, X and Yang, L and Peng, B and Xie, G and Cheng, W and Hao, B and Li, C and Xia, J and Zhang, B}, title = {Complete Genome Sequence of Clostridium kluyveri JZZ Applied in Chinese Strong-Flavor Liquor Production.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1429-1433}, pmid = {30030563}, issn = {1432-0991}, support = {J01001935//Initial Foundation of Doctoral Scientific Research in Anhui University/ ; }, mesh = {Bacterial Proteins/genetics/metabolism ; Base Sequence ; Caproates/metabolism ; China ; Clostridium kluyveri/*genetics/isolation & purification/metabolism ; Ethanol/metabolism ; Fermentation ; Flavoring Agents/metabolism ; *Genome, Bacterial ; Wine/*microbiology ; }, abstract = {Chinese strong-flavor liquor (CSFL), accounting for more than 70% of both Chinese liquor production and sales, was produced by complex fermentation with pit mud. Clostridium kluyveri, an important species coexisted with other microorganisms in fermentation pit mud (FPM), could produce caproic acid, which was subsequently converted to the key CSFL flavor substance ethyl caproate. In this study, we present the first complete genome sequence of C. kluyveri isolated from FPM. Clostridium kluyveri JZZ contains one circular chromosome and one circular plasmid with length of 4,454,353 and 58,581 bp, respectively. 4158 protein-coding genes were predicted and 2792 genes could be assigned with COG categories. It possesses the pathway predicted for biosynthesis of caproic acid with ethanol. Compared to other two C. kluyveri genomes, JZZ consists of longer chromosome with multiple gene rearrangements, and contains more genes involved in defense mechanisms, as well as DNA replication, recombination, and repair. Meanwhile, JZZ contains fewer genes involved in secondary metabolites biosynthesis, transport, and catabolism, including genes encoding Polyketide Synthases/Non-ribosomal Peptide Synthetases. Additionally, JZZ possesses 960 unique genes with relatively aggregating in defense mechanisms and transcription. Our study will be available for further research about C. kluyveri isolated from FPM, and will also facilitate the genetic engineering to increase biofuel production and improve fragrance flavor of CSFL.}, } @article {pmid30030562, year = {2018}, author = {Dasgupta, A and Saikia, R and Handique, PJ}, title = {Mapping the Bacterial Community in Digboi Oil Refinery, India by High-Throughput Sequencing Approach.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1441-1446}, pmid = {30030562}, issn = {1432-0991}, support = {INDEPTH//Council of Scientific and Industrial Research/ ; }, mesh = {Bacteria/classification/genetics/*isolation & purification ; *Biodiversity ; High-Throughput Nucleotide Sequencing ; India ; Oil and Gas Industry ; Phylogeny ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {Microbial enhanced oil recovery (MOER) is a technique which uses microbes to enhance the oil recovery process. This technique is advantageous to enhance oil recovery (EOR). In this study, we analyzed the bacterial communities of Digboi oil refinery and its surroundings using Illumina MiSeq sequencing platform. A total of 12 samples were analyzed, 6 from inside the refinery areas and another 6 from the township areas. Alpha diversity studies indicated that diversity of bacterial communities in township area was higher than the refinery areas except for Sample 1. Sample 9 from the nearby pond of Digboi Centenary Park was more diverse in community composition. Proteobacteria was found to be most dominant phylum. Mantel test indicated that environmental factors had negative influence over the bacterial community structure. Among the environmental factors Fe was least significant (r2 = 0.368) as indicated by canonical correspondence analysis.}, } @article {pmid30030513, year = {2018}, author = {Gompel, N and Prud'homme, B}, title = {Neural circuit evolved to process pheromone differently in two species of fruit fly.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {485-487}, doi = {10.1038/d41586-018-05595-y}, pmid = {30030513}, issn = {1476-4687}, } @article {pmid30030512, year = {2018}, author = {Kappelman, J}, title = {An early hominin arrival in Asia.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {480-481}, doi = {10.1038/d41586-018-05293-9}, pmid = {30030512}, issn = {1476-4687}, } @article {pmid30030511, year = {2018}, author = {Frezza, C}, title = {Histidine metabolism boosts cancer therapy.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {484-485}, doi = {10.1038/d41586-018-05573-4}, pmid = {30030511}, issn = {1476-4687}, } @article {pmid30030285, year = {2018}, author = {Scully, MO and Fulling, S and Lee, DM and Page, DN and Schleich, WP and Svidzinsky, AA}, title = {Quantum optics approach to radiation from atoms falling into a black hole.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8131-8136}, pmid = {30030285}, issn = {1091-6490}, abstract = {We show that atoms falling into a black hole (BH) emit acceleration radiation which, under appropriate initial conditions, looks to a distant observer much like (but is different from) Hawking BH radiation. In particular, we find the entropy of the acceleration radiation via a simple laser-like analysis. We call this entropy horizon brightened acceleration radiation (HBAR) entropy to distinguish it from the BH entropy of Bekenstein and Hawking. This analysis also provides insight into the Einstein principle of equivalence between acceleration and gravity.}, } @article {pmid30030284, year = {2018}, author = {Edwards, BFL and Wheeler, RJ and Barker, AR and Moreira-Leite, FF and Gull, K and Sunter, JD}, title = {Direction of flagellum beat propagation is controlled by proximal/distal outer dynein arm asymmetry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7341-E7350}, pmid = {30030284}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 103261/Z/13/Z//Wellcome Trust/United Kingdom ; 108445/Z/15/Z//Wellcome Trust/United Kingdom ; 104627/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Axoneme/chemistry ; Dyneins/*chemistry ; Flagella/chemistry/*physiology ; Protein Multimerization ; }, abstract = {The 9 + 2 axoneme structure of the motile flagellum/cilium is an iconic, apparently symmetrical cellular structure. Recently, asymmetries along the length of motile flagella have been identified in a number of organisms, typically in the inner and outer dynein arms. Flagellum-beat waveforms are adapted for different functions. They may start either near the flagellar tip or near its base and may be symmetrical or asymmetrical. We hypothesized that proximal/distal asymmetry in the molecular composition of the axoneme may control the site of waveform initiation and the direction of waveform propagation. The unicellular eukaryotic pathogens Trypanosoma brucei and Leishmania mexicana often switch between tip-to-base and base-to-tip waveforms, making them ideal for analysis of this phenomenon. We show here that the proximal and distal portions of the flagellum contain distinct outer dynein arm docking-complex heterodimers. This proximal/distal asymmetry is produced and maintained through growth by a concentration gradient of the proximal docking complex, generated by intraflagellar transport. Furthermore, this asymmetry is involved in regulating whether a tip-to-base or base-to-tip beat occurs, which is linked to a calcium-dependent switch. Our data show that the mechanism for generating proximal/distal flagellar asymmetry can control waveform initiation and propagation direction.}, } @article {pmid30030180, year = {2018}, author = {Aghová, T and Kimura, Y and Bryja, J and Dobigny, G and Granjon, L and Kergoat, GJ}, title = {Fossils know it best: Using a new set of fossil calibrations to improve the temporal phylogenetic framework of murid rodents (Rodentia: Muridae).}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {98-111}, doi = {10.1016/j.ympev.2018.07.017}, pmid = {30030180}, issn = {1095-9513}, abstract = {Murid rodents (Rodentia: Muridae) represent the most diverse and abundant mammalian family. In this study, we provide a refined set of fossil calibrations which is used to reconstruct a dated phylogeny of the family using a multilocus dataset (six nuclear and nine mitochondrial gene fragments) encompassing 161 species representing 82 murid genera from four extant subfamilies (Deomyinae, Gerbillinae, Lophiomyinae and Murinae). In comparison with previous studies on murid or muroid rodents, our work stands out for the implementation of nine robust fossil constraints within the Muridae thanks to a thorough review of the fossil record. Before being assigned to specific nodes of the phylogeny, all potential fossil constraints were carefully assessed; they were also subjected to several cross-validation analyses. The resulting phylogeny is consistent with previous phylogenetic studies on murids, and recovers the monophyly of all sampled murid subfamilies and tribes. Based on nine controlled fossil calibrations, our inferred temporal timeframe indicates that the murid family likely originated in the course of the Early Miocene, 22.0-17.0 million years ago (Ma), and that most major lineages (i.e. tribes) started diversifying ca. 10 Ma. Historical biogeography analyses support the tropical origin for the family, with an initial internal split (vicariance event) between Afrotropical and Oriental (Indomalaya and Philippines) lineages. During the course of their diversification, the biogeographic pattern of murids is marked by several dispersal events toward the Australasian and the Palearctic regions. The Afrotropical region was also secondarily colonized at least three times from the Indomalaya, indicating that the latter region has acted as a major centre of diversification for the family.}, } @article {pmid30030179, year = {2018}, author = {Chan, KO and Grismer, LL and Brown, RM}, title = {Comprehensive multi-locus phylogeny of Old World tree frogs (Anura: Rhacophoridae) reveals taxonomic uncertainties and potential cases of over- and underestimation of species diversity.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {1010-1019}, doi = {10.1016/j.ympev.2018.07.005}, pmid = {30030179}, issn = {1095-9513}, abstract = {The family Rhacophoridae is one of the most diverse amphibian families in Asia, for which taxonomic understanding is rapidly-expanding, with new species being described steadily, and at increasingly finer genetic resolution. Distance-based methods frequently have been used to justify or at least to bolster the recognition of new species, particularly in complexes of "cryptic" species where obvious morphological differentiation does not accompany speciation. However, there is no universally-accepted threshold to distinguish intra- from interspecific genetic divergence. Moreover, indiscriminant use of divergence thresholds to delimit species can result in over- or underestimation of species diversity. To explore the range of variation in application of divergence scales, and to provide a family-wide assessment of species-level diversity in Old-World treefrogs (family Rhacophoridae), we assembled the most comprehensive multi-locus phylogeny to date, including all 18 genera and approximately 247 described species (∼60% coverage). We then used the Automatic Barcode Gap Discovery (ABGD) method to obtain different species-delimitation schemes over a range of prior intraspecific divergence limits to assess the consistency of divergence thresholds used to demarcate current species boundaries. The species-rich phylogeny was able to identify a number of taxonomic errors, namely the incorrect generic placement of Chiromantis inexpectatus, which we now move to the genus Feihyla, and the specific identity of Rhacophorus bipunctatus from Peninsular Malaysia, which we tentatively reassign to R. rhodopus. The ABGD analysis demonstrated overlap between intra- and interspecific divergence limits: genetic thresholds used in some studies to synonymize taxa have frequently been used in other studies to justify the recognition of new species. This analysis also highlighted numerous groups that could potentially be split or lumped, which we earmark for future examination. Our large-scale and en bloc approach to species-level phylogenetic systematics contributes to the resolution of taxonomic uncertainties, reveals possible new species, and identifies numerous groups that require critical examination. Overall, we demonstrate that the taxonomy and evolutionary history of Old-World tree frogs are far from resolved, stable or adequately characterized at the level of genus, species, and/or population.}, } @article {pmid30029803, year = {2019}, author = {Charlier, P and Gaultier, F and Héry-Arnaud, G}, title = {Interbreeding between Neanderthals and modern humans: Remarks and methodological dangers of a dental calculus microbiome analysis.}, journal = {Journal of human evolution}, volume = {126}, number = {}, pages = {124-126}, doi = {10.1016/j.jhevol.2018.06.007}, pmid = {30029803}, issn = {1095-8606}, } @article {pmid30029618, year = {2018}, author = {López-González, MJ and Campelo, AB and Picon, A and Rodríguez, A and Martínez, B}, title = {Resistance to bacteriocin Lcn972 improves oxygen tolerance of Lactococcus lactis IPLA947 without compromising its performance as a dairy starter.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {76}, pmid = {30029618}, issn = {1471-2180}, abstract = {BACKGROUND: Lactococcus lactis is the main component of the mesophilic starters used in cheese manufacture. The success of milk fermentation relies on the viability and metabolic activity of the starter bacteria. Therefore, robust strains able to withstand the harsh conditions encountered during cheese manufacture and starter production are demanded. In this work, we have applied adaptive evolution under cell envelope stress imposed by the cell wall active bacteriocin Lcn972 to evolve strains with more robust phenotypes.

RESULTS: Consecutive exposure of the starter strain L. lactis IPLA947 to Lcn972 yielded a stable mutant, L. lactis R5, with enhanced survival when challenged with hydrogen peroxide. L. lactis R5 exhibited faster growth rates in aerobic fermentations in broth and was able to acidify milk to a lower pH in aerated milk cultures. The improved behavior of L. lactis R5 in the presence of oxygen did not translate into a better performance in the presence of heme (i.e. respiration metabolism) or into higher survival during storage at cold temperatures or after freeze-drying compared to the wild type L. lactis IPLA947. L. lactis R5 retained the same milk acidification rate and no changes in the consumption of lactose and production of organic acids were noticed. However, the profile of volatile compounds revealed a significant increase in 3-hydroxy-2-butanone (acetoin) in curds manufactured with L. lactis R5.

CONCLUSIONS: Based on our results, L. lactis R5 can be proposed as a suitable dairy starter with improved survival under oxidative stress and enhanced metabolic traits. The results support the notion that adaptive evolution under cell envelope stress might be useful to generate strain diversity within industrial L. lactis strains.}, } @article {pmid30029615, year = {2018}, author = {Lekana-Douki, SE and Behillil, S and Enouf, V and Leroy, EM and Berthet, N}, title = {Detection of human bocavirus-1 in both nasal and stool specimens from children under 5 years old with influenza-like illnesses or diarrhea in Gabon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {495}, pmid = {30029615}, issn = {1756-0500}, mesh = {Child, Preschool ; Diarrhea/*virology ; Female ; Gabon ; Human bocavirus/*isolation & purification ; Humans ; Infant ; Influenza A Virus, H1N1 Subtype ; Influenza, Human/*virology ; Male ; Parvoviridae Infections ; Prevalence ; Respiratory Tract Infections ; Retrospective Studies ; }, abstract = {OBJECTIVE: Human bocavirus (HBoV) is a viral pathogen which causes respiratory tract diseases and acute gastroenteritis worldwide. This virus mainly affected children under 5 years old. There is little information on HBoV in Gabon. Two first studies was conducted to determine the prevalence of respiratory and enteric viruses in children under 5 years old who visited health centers for influenza-like illness (ILI) or diarrhea in Gabon from March 2010 to June 2011. However, HBoV was not included in the screening. The aim of this retrospective study was to evaluate the prevalence and the HBoV genotype in children under 5 years old with ILI or diarrhea in Gabon.

RESULTS: A total of 810 nasal swabs and 317 feces samples collected during the two first study were analyzed among which 32 (4.4%) and 7 (2.2%) were positive for HBoV respectively. While there were no significant differences in prevalence between age groups in children with ILI, all children with diarrhea were under 12 months of age. Moreover, 84.4 and 42.8% were diagnosed in co-infections with at least one other respiratory virus, or enteric viruses respectively. Finally, HBoV subtype 1 has been detected in both respiratory and gastrointestinal tracts with very low variability.}, } @article {pmid30029614, year = {2018}, author = {Tasew, H and Zemicheal, M and Teklay, G and Mariye, T and Ayele, E}, title = {Risk factors of birth asphyxia among newborns in public hospitals of Central Zone, Tigray, Ethiopia 2018.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {496}, pmid = {30029614}, issn = {1756-0500}, support = {AKUR00024/2010E.C//Aksum University/ ; }, mesh = {Asphyxia Neonatorum/*epidemiology ; Ethiopia ; Female ; *Hospitals, Public ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Male ; Pregnancy ; Premature Birth ; Risk Factors ; }, abstract = {OBJECTIVE: The aim of study was to identify risk factors of birth asphyxia among newborns in public hospitals of Central Zone Tigray, Ethiopia 2018.

RESULTS: A total of 88 cases and 176 controls were included in the study. Thirty (34.1%) cases and 28 (15.9%) of controls were not able to read and write. Twenty-one (23.9%) cases and 9 (5.1%) controls were had meconium stained on pelvic examination. Multivariable logistic regression analysis showed that maternal illiteracy [AOR = 6; 95% CI (1.51, 23.80)], low birth weight [AOR = 6.9; 95% CI (3.01, 15.81)], preterm [AOR = 2.2; 95% CI (1.022, 4.76)], prim parous [AOR = 3.1; 95% CI (1.51, 6.38)], antepartum hemorrhage [AOR = 12; 95% CI (2.29, 63.11)] and meconium stained amniotic fluid [AOR = 7.88; 95% CI (2.92, 21.29)] were independent risk factors of birth asphyxia.}, } @article {pmid30029611, year = {2018}, author = {Chastain, DB and King, ST and Stover, KR}, title = {Rethinking urinary antibiotic breakpoints: analysis of urinary antibiotic concentrations to treat multidrug resistant organisms.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {497}, pmid = {30029611}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/*urine ; Ciprofloxacin/urine ; *Drug Resistance, Bacterial ; Fluoroquinolones/urine ; Humans ; Microbial Sensitivity Tests ; Pseudomonas aeruginosa/*drug effects ; }, abstract = {OBJECTIVE: The present study analyzed whether renally eliminated antibiotics achieve sufficient urinary concentrations based on their pharmacokinetic/pharmacodynamic principles to effectively eradicate organisms deemed resistant by automated susceptibility testing.

RESULTS: Lower median minimum inhibitory concentrations against enterobacteriaceae were noted for ceftriaxone, cefepime, and doripenem when comparing Etest® to Vitek®. All Pseudomonas aeruginosa isolates were susceptible to cefepime, ciprofloxacin, and doripenem with both susceptibility methods, but higher median minimum inhibitory concentrations were observed with Etest®. Urine concentrations/time profiles were calculated for standard doses of ceftriaxone, cefepime, doripenem, and ciprofloxacin. The data presented in the current study suggests high urine concentrations of antibiotics may effectively eradicate bacteria which were determined to be resistant per in vitro susceptibility testing.}, } @article {pmid30029596, year = {2018}, author = {Wang, L and Xi, Y and Sung, S and Qiao, H}, title = {RNA-seq assistant: machine learning based methods to identify more transcriptional regulated genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {546}, pmid = {30029596}, issn = {1471-2164}, support = {NIH-1R01GM115879-01//National Institutes of Health/ ; R01 GM115879/GM/NIGMS NIH HHS/United States ; R01 GM100108/GM/NIGMS NIH HHS/United States ; NSF IOS 1656764//National Science Foundation/ ; NIH-2R01GM100108//National Institutes of Health/ ; }, mesh = {Arabidopsis/genetics/metabolism ; *Epigenesis, Genetic ; Gene Expression Profiling/*methods ; Histone Code ; Humans ; *Machine Learning ; Sequence Analysis, RNA/*methods ; Transcription, Genetic ; }, abstract = {BACKGROUND: Although different quality controls have been applied at different stages of the sample preparation and data analysis to ensure both reproducibility and reliability of RNA-seq results, there are still limitations and bias on the detectability for certain differentially expressed genes (DEGs). Whether the transcriptional dynamics of a gene can be captured accurately depends on experimental design/operation and the following data analysis processes. The workflow of subsequent data processing, such as reads alignment, transcript quantification, normalization, and statistical methods for ultimate identification of DEGs can influence the accuracy and sensitivity of DEGs analysis, producing a certain number of false-positivity or false-negativity. Machine learning (ML) is a multidisciplinary field that employs computer science, artificial intelligence, computational statistics and information theory to construct algorithms that can learn from existing data sets and to make predictions on new data set. ML-based differential network analysis has been applied to predict stress-responsive genes through learning the patterns of 32 expression characteristics of known stress-related genes. In addition, the epigenetic regulation plays critical roles in gene expression, therefore, DNA and histone methylation data has been shown to be powerful for ML-based model for prediction of gene expression in many systems, including lung cancer cells. Therefore, it is promising that ML-based methods could help to identify the DEGs that are not identified by traditional RNA-seq method.

RESULTS: We identified the top 23 most informative features through assessing the performance of three different feature selection algorithms combined with five different classification methods on training and testing data sets. By comprehensive comparison, we found that the model based on InfoGain feature selection and Logistic Regression classification is powerful for DEGs prediction. Moreover, the power and performance of ML-based prediction was validated by the prediction on ethylene regulated gene expression and the following qRT-PCR.

CONCLUSIONS: Our study shows that the combination of ML-based method with RNA-seq greatly improves the sensitivity of DEGs identification.}, } @article {pmid30029595, year = {2018}, author = {Shi, W and Wen, D and Chen, C and Yuan, L and Gao, W and Tang, P and Cheng, X and Yao, K}, title = {β-Lactamase production and antibiotic susceptibility pattern of Moraxella catarrhalis isolates collected from two county hospitals in China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {77}, pmid = {30029595}, issn = {1471-2180}, abstract = {BACKGROUND: Moraxella catarrhalis (M. catarrhalis) is an important bacterial pathogen. However, its antibiotic susceptibility patterns in different areas are difficult to compare because of the use of different methods and judgement criteria. This study aimed to determine antimicrobial susceptibility and β-lactamase activity characteristics of M. catarrhalis isolates collected from two county hospitals in China, and to express the results with reference to three commonly used judgement criteria.

RESULTS: Nasopharyngeal swabs were obtained from child inpatients with respiratory tract infections at the People's Hospital of Zhongjiang County and Youyang County from January to December 2015. M. catarrhalis strains were isolated and identified from the swabs, and susceptibility against 11 antimicrobials was determined using the E-test method or disc diffusion. Test results were interpreted with reference to the standards of the European Committee on Antimicrobial Susceptibility Testing (EUCAST), the Clinical and Laboratory Standards Institute (CLSI), and the British Society for Antimicrobial Chemotherapy (BSAC). Detection of β-lactamase activity was determined by the chromogenic cephalosporin nitrocefin. M. catarrhalis yield rates were 7.12 and 9.58% (Zhongjiang County, 77/1082 cases; Youyang County, 101/1054 cases, respectively). All isolates were susceptible to amoxicillin-clavulanic acid. The susceptibility rate to meropenem was 100% according to EUCAST; no breakpoints were listed in CLSI or BSAC. The non-susceptibility rate to sulfamethoxazole-trimethoprim differed significantly between the two hospitals regardless of the judgemnet criteria used, with isolates from Zhongjiang showing higher susceptibility to those from Youyang (Fisher's exact test, P < 0.05). According to CLSI, the total non-susceptibility rate to erythromycin was 70.8% (Zhongjiang County, 79.2%; Youyang County, 64.3%), and the rate reached 92.1% (Zhongjiang County, 90.9%; Youyang County, 93.1%) on the basis of EUCAST or BSAC. The total positive rate of β-lactamase was 99.4% (177/178 cases) (Zhongjiang County, 100%, 77/77 cases; Youyang County, 99.0%, 100/101 cases).

CONCLUSIONS: Ninety nine percent of M. catarrhalis isolates produce β-lactamase. The isolates showed poor susceptibility to ampicillin and erythromycin, and high susceptibility to the third- and fourth-generation cephalosporins and amoxicillin-clavulanic. Significant discrepancies between different antimicrobial susceptibility judgemnet criteria were noted.}, } @article {pmid30029594, year = {2018}, author = {Dou, Y and Zhu, Y and Ai, J and Chen, H and Liu, H and Borgia, JA and Li, X and Yang, F and Jiang, B and Wang, J and Deng, Y}, title = {Plasma small ncRNA pair panels as novel biomarkers for early-stage lung adenocarcinoma screening.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {545}, pmid = {30029594}, issn = {1471-2164}, support = {5P30GM114737//the NIH Grant/ ; P20 GM103466/GM/NIGMS NIH HHS/United States ; 1R21 CA164764//NIH grant/ ; U54 MD007601/MD/NIMHD NIH HHS/United States ; P30 GM114737/GM/NIGMS NIH HHS/United States ; JCYJ20150402095058885//Shenzhen Science and Technology Project/ ; U54 MD007584/MD/NIMHD NIH HHS/United States ; U54 MD007584//the NIH Grant/ ; P20GM103466//the NIH Grant/ ; R21 CA164764/CA/NCI NIH HHS/United States ; }, mesh = {Adenocarcinoma/*diagnosis ; Adult ; Aged ; Aged, 80 and over ; Biomarkers/blood ; Early Detection of Cancer ; Female ; Humans ; Lung Neoplasms/*diagnosis ; Male ; Middle Aged ; RNA, Small Untranslated/*blood ; Young Adult ; }, abstract = {BACKGROUND: Lung cancer is a major cause of cancer-related mortality worldwide, and around two-thirds of patients have metastasis at diagnosis. Thus, detecting lung cancer at an early stage could reduce mortality. Aberrant levels of circulating small non-coding RNAs (small ncRNAs) are potential diagnostic or prognostic markers for lung cancer. We aimed to identify plasma small ncRNA pairs that could be used for early screening and detection of lung adenocarcinoma (LAC).

RESULTS: A panel of seven small ncRNA pair ratios could differentiate patients with LAC or benign lung disease from high-risk controls with an area under the curve (AUC) of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage (which included 50 patients with early-stage LAC, 35 patients with benign diseases and 29 high-risk controls) and an AUC of 90.2%, a sensitivity of 91.5% and a specificity of 80.4% at the validation stage (which included 44 patients with early-stage LAC, 32 patients with benign diseases and 51 high-risk controls). The same panel could distinguish LAC from high-risk controls with an AUC of 100.0%, a sensitivity of 100.0% and a specificity of 100.0% at the training stage and an AUC of 89.5%, a sensitivity of 85.4% and a specificity of 83.3% at the validation stage. Another panel of five small ncRNA pair ratios (different from the first) was able to differentiate LAC from benign disease with an AUC of 82.0%, a sensitivity of 81.1% and a specificity of 78.1% in the training cohort and an AUC of 74.2%, a sensitivity of 70.4% and a specificity of 72.7% in the validation cohort.

CONCLUSIONS: Several small ncRNA pair ratios were identified as markers capable of discerning patients with LAC from those with benign lesions or high-risk control individuals.}, } @article {pmid30029593, year = {2018}, author = {Sharma, P and Caraguel, C and Sexton, M and McWhorter, A and Underwood, G and Holden, K and Chousalkar, K}, title = {Shedding of Salmonella Typhimurium in vaccinated and unvaccinated hens during early lay in field conditions: a randomised controlled trial.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {78}, pmid = {30029593}, issn = {1471-2180}, abstract = {BACKGROUND: Salmonella vaccination is one of the control measure that farmers can use to reduce bacterial shedding in their flocks. This study aimed to examine the efficacy of the Vaxsafe® ST (Strain STM-1) attenuated live vaccine administered as ocular and oral doses followed by an intramuscular (IM) dose in rearing, in reducing contamination by Salmonellae of both eggs and the environment in the commercial multi-age cage layer sheds. A randomised controlled trial was conducted up to 26 weeks post last vaccine on two different multi-age caged egg farms.

RESULTS: No clinical symptoms were observed following IM administration of STM-1 during rearing. Following the first two STM-1 doses, both vaccinated and unvaccinated birds exhibited antibody titres below the positive cut-off value, however after IM administration of STM-1, antibody titres in the vaccinated group were above the cut-off value. Wild type Salmonella Typhimurium was not detected during the rearing of pullets. During production, the antibody titres were significantly higher in the vaccinated group at all sampling points during this trial. There was no significant difference in the prevalence of Salmonella (detected by culture and PCR method) between the vaccinated and unvaccinated groups on the egg belt and faeces in early lay. Wild-type Salmonella spp. were consistently found in dust samples. Quantitative PCR (qPCR) assay was able to differentiate between the live vaccine strain and wild type Salmonella. The load of wild-type Salmonella in shed environment was relatively low (1.3 log10 ± 0.48 CFU/m2 of surface area).

CONCLUSION: Given that Salmonella Typhimurium and other serovars are able to survive/persist in the shed environment (such as in dust), regular cleaning and or removal of dust from shed is important. Use of the Vaxsafe® ST vaccine in multi-age flocks is "not an ultimate intervention" for reduction of Salmonella Typhimurium because of the complexities involved in achieving control, such as the efficacy of cleaning of sheds, the lack of resting periods between batches and the possible carry over of contamination from existing flocks. Hence implementation of more than one or several interventions strategies is essential.}, } @article {pmid30029592, year = {2018}, author = {Tian, Z and Sun, L and Li, Y and Quan, L and Zhang, H and Yan, W and Yue, Q and Qiu, G}, title = {Antennal transcriptome analysis of the chemosensory gene families in Carposina sasakii (Lepidoptera: Carposinidae).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {544}, pmid = {30029592}, issn = {1471-2164}, support = {No. 31601643//National Natural Science Foundation of China/ ; No. 1610182016004//Fundamental Research Funds for Central Non-Profit Scientific Insititution/ ; }, mesh = {Animals ; Arthropod Antennae/*metabolism ; Female ; Gene Expression Profiling ; Insect Proteins/*genetics ; Male ; Membrane Proteins/genetics ; Moths/*genetics/metabolism ; *Multigene Family ; Organ Specificity ; Receptors, Odorant/genetics ; Sex Factors ; }, abstract = {BACKGROUND: The peach fruit moth, Carposina sasakii Matsumura (Lepidoptera: Carposinidae), poses a serious threat to a variety of fruits and causes significant economic loss owing to difficulties in its prevention and control. The olfactory sense is generally acknowledged to be a novel target for pest control. However, a systematic study of the olfactory genes expressed in C. sasakii has not been reported yet. Here, we reported the antennal transcriptome of C. sasakii using high-throughput sequencing and annotated the main chemosensory multi-gene families.

RESULTS: In the chemosensory gene families, 29 odorant-binding proteins, 13 chemosensory proteins, 1 sensory neuron membrane protein, 52 odorant receptors, 8 ionotropic receptors and 11 gustatory receptors were annotated in the C. sasakii antennal transcriptome. The number of olfactory genes obtained in our transcriptome was consistent with that identified in other lepidopteran insects, confirming that we basically accomplished the annotation of the chemosensory genes of C. sasakii in the adult antennal transcriptome. All sequences were annotated and analyzed by BLAST (basic local alignment search tool), and some chemosensory genes with specific functions were named according to the BLAST results and phylogenetic trees. Based on the expression profile in the transcriptome and phylogenetic analysis, differentially expressed genes (DEGs) were analyzed in both male and female adults. Finally, fluorescence quantitative real-time PCR was used to identify the male-specific or female-specific chemosensory genes that were putatively related to odor detection and recognition. Moreover, expression levels of OR33 and PBP2 were significantly higher in males than in females, indicating that these genes may interact with sex pheromones. We found some conserved antennal IRs and GRs involved in detecting sugar compounds (GR2, GR5, GR6, GR8) and carbon dioxide (GR1), which were also identified based on phylogenetic analysis.

CONCLUSIONS: There are 114 putative chemosensory proteins expressed in C. sasakii identified in this study. The identification of these proteins will make the molecular mechanism of odor recognition accessible.}, } @article {pmid30029591, year = {2018}, author = {Franke, KR and Schmidt, SA and Park, S and Jeong, DH and Accerbi, M and Green, PJ}, title = {Analysis of Brachypodium miRNA targets: evidence for diverse control during stress and conservation in bioenergy crops.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {547}, pmid = {30029591}, issn = {1471-2164}, support = {P20 GM103446/GM/NIGMS NIH HHS/United States ; T32 GM008550/GM/NIGMS NIH HHS/United States ; DE-FG02-07ER64450//U.S. Department of Energy/ ; T32 GM008550/GM/NIGMS//National Institutes of Health/ ; }, mesh = {Brachypodium/*genetics/metabolism ; Cold Temperature ; Crops, Agricultural/genetics ; Gene Expression Regulation, Plant ; MicroRNAs/*metabolism ; Panicum/genetics ; RNA Cleavage ; RNA, Messenger/*metabolism ; Sequence Analysis, RNA ; Sorghum/genetics ; Stress, Physiological/genetics ; }, abstract = {BACKGROUND: Since the proposal of Brachypodium distachyon as a model for the grasses, over 500 Bdi-miRNAs have been annotated in miRBase making Brachypodium second in number only to rice. Other monocots, such as switchgrass, are completely absent from the miRBase database. While a significant number of miRNAs have been identified which are highly conserved across plants, little research has been done with respect to the conservation of miRNA targets. Plant responses to abiotic stresses are regulated by diverse pathways many of which involve miRNAs; however, it can be difficult to identify miRNA guided gene regulation when the miRNA is not the primary regulator of the target mRNA.

RESULTS: To investigate miRNA target conservation and stress response involvement, a set of PARE (Parallel Analysis of RNA Ends) libraries totaling over two billion reads was constructed and sequenced from Brachypodium, switchgrass, and sorghum representing the first report of RNA degradome data from the latter two species. Analysis of this data provided not only PARE evidence for miRNA guided cleavage of over 7000 predicted target mRNAs in Brachypodium, but also evidence for miRNA guided cleavage of over 1000 homologous transcripts in sorghum and switchgrass. A pipeline was constructed to compare RNA-seq and PARE data made from Brachypodium plants exposed to various abiotic stress conditions. This resulted in the identification of 44 miRNA targets which exhibit stress regulated cleavage. Time course experiments were performed to reveal the relationship between miR393ab, miR169a, miR394ab, and their respective targets throughout the first 36 h of the cold stress response in Brachypodium.

CONCLUSIONS: Knowledge gained from this study provides considerable insight into the RNA degradomes and the breadth of miRNA target conservation among these three species. Additionally, associations of a number of miRNAs and target mRNAs with the stress responses have been revealed which could aid in the development of stress tolerant transgenic crops.}, } @article {pmid30029590, year = {2018}, author = {He, J and Gao, Y and Wu, G and Lei, X and Zhang, Y and Pan, W and Yu, H}, title = {Molecular mechanism of estrogen-mediated neuroprotection in the relief of brain ischemic injury.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {46}, pmid = {30029590}, issn = {1471-2156}, support = {81270435//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: This study aimed to explore the molecular mechanism of estrogen-mediated neuroprotection in the relief of cerebral ischemic injury. The gene expression profiles were downloaded from Gene Expression Omnibus database, and differentially expressed genes (DEGs) were identified using limma package in R software. Further, DEGs were subjected to Gene Ontology (GO) cluster analysis using online Gene Ontology Enrichment Analysis Software Toolkit and to GO functional enrichment analysis using DAVID software. Using the Gene Set Analysis Toolkit V2, enrichment analysis of Kyoto Encyclopedia of Genes and Genomes pathways was performed. In addition, protein-protein interaction (PPI) network was constructed using STRING database, and submodule analysis of PPI network. Lastly, the significant potential target sites of microRNAs (miRNAs) were predicted using Molecular Signatures Database, and the function analysis of targets of predicted miRNA was also performed using DAVID software.

RESULTS: In total, 321 DEGs were screened in the estrogen-treated sample. The DEGs were mainly associated with intracellular signaling and metabolic pathways, such as calcium channel, calcineurin complex, insulin secretion, low-density lipoprotein reconstruction, and starch or sugar metabolism. In addition, GO enrichment analysis indicated an altered expression of the genes related to starch and sucrose metabolism, retinol metabolism, anti-apoptosis (eg., BDNF and ADAM17) and response to endogenous stimulus. The constructed PPI network comprised of 243 nodes and 590 interaction pairs, and four submodules were obtained from PPI network. Among the module d, four glutamate receptors as Gria4, Gria3, Grin3a and Grik4 were highlighted. Further, 5 novel potential regulatory miRNAs were also predicted. MIR-338 and MIR520D were closely associated with cell cycle, while the targets of MIR-376A and MIR-376B were only involved in cell soma.

CONCLUSIONS: The DEGs in estrogen-treated samples are closely associated with calcium channel, glutamate induced excitotoxicity and anti-apoptotic activity. In addition, some functionally significant DEGs such as BDNF, ADAM17, Gria4, Gria3, Grin3a, Grik4, Gys2 and Ugtla2, and new miRNAs like MIR-338 and MIR-376A were identified, which may serve as potential therapeutic targets for the effective treatment of cerebral ischemic injury.}, } @article {pmid30028643, year = {2018}, author = {Mogessie, B and Scheffler, K and Schuh, M}, title = {Assembly and Positioning of the Oocyte Meiotic Spindle.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {381-403}, doi = {10.1146/annurev-cellbio-100616-060553}, pmid = {30028643}, issn = {1530-8995}, abstract = {Fertilizable eggs develop from diploid precursor cells termed oocytes. Once every menstrual cycle, an oocyte matures into a fertilizable egg in the ovary. To this end, the oocyte eliminates half of its chromosomes into a small cell termed a polar body. The egg is then released into the Fallopian tube, where it can be fertilized. Upon fertilization, the egg completes the second meiotic division, and the mitotic division of the embryo starts. This review highlights recent work that has shed light on the cytoskeletal structures that drive the meiotic divisions of the oocyte in mammals. In particular, we focus on how mammalian oocytes assemble a microtubule spindle in the absence of centrosomes, how they position the spindle in preparation for polar body extrusion, and how the spindle segregates the chromosomes. We primarily focus on mouse oocytes as a model system but also highlight recent insights from human oocytes.}, } @article {pmid30028642, year = {2018}, author = {Furlanis, E and Scheiffele, P}, title = {Regulation of Neuronal Differentiation, Function, and Plasticity by Alternative Splicing.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {451-469}, doi = {10.1146/annurev-cellbio-100617-062826}, pmid = {30028642}, issn = {1530-8995}, abstract = {Posttranscriptional mechanisms provide powerful means to expand the coding power of genomes. In nervous systems, alternative splicing has emerged as a fundamental mechanism not only for the diversification of protein isoforms but also for the spatiotemporal control of transcripts. Thus, alternative splicing programs play instructive roles in the development of neuronal cell type-specific properties, neuronal growth, self-recognition, synapse specification, and neuronal network function. Here we discuss the most recent genome-wide efforts on mapping RNA codes and RNA-binding proteins for neuronal alternative splicing regulation. We illustrate how alternative splicing shapes key steps of neuronal development, neuronal maturation, and synaptic properties. Finally, we highlight efforts to dissect the spatiotemporal dynamics of alternative splicing and their potential contribution to neuronal plasticity and the mature nervous system.}, } @article {pmid30028641, year = {2018}, author = {Sherman, MH}, title = {Stellate Cells in Tissue Repair, Inflammation, and Cancer.}, journal = {Annual review of cell and developmental biology}, volume = {34}, number = {}, pages = {333-355}, doi = {10.1146/annurev-cellbio-100617-062855}, pmid = {30028641}, issn = {1530-8995}, abstract = {Stellate cells are resident lipid-storing cells of the pancreas and liver that transdifferentiate to a myofibroblastic state in the context of tissue injury. Beyond having roles in tissue homeostasis, stellate cells are increasingly implicated in pathological fibrogenic and inflammatory programs that contribute to tissue fibrosis and that constitute a growth-permissive tumor microenvironment. Although the capacity of stellate cells for extracellular matrix production and remodeling has long been appreciated, recent research efforts have demonstrated diverse roles for stellate cells in regulation of epithelial cell fate, immune modulation, and tissue health. Our present understanding of stellate cell biology in health and disease is discussed here, as are emerging means to target these multifaceted cells for therapeutic benefit.}, } @article {pmid30028475, year = {2018}, author = {Piazza, A and Comandatore, F and Romeri, F and Pagani, C and Mattioni Marchetti, V and Brilli, M and Panelli, S and Migliavacca, R and Ridolfo, A and Olivieri, P and Gismondo, MR and Bandi, C and Rimoldi, SG}, title = {Detection of ST1702 Escherichia coli blaNDM-5 and blaCMY-42 genes positive isolates from a Northern Italian hospital.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {230-231}, pmid = {30028475}, issn = {1121-7138}, mesh = {Aged ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins ; Escherichia coli/*genetics/*isolation & purification ; Escherichia coli Infections/epidemiology/microbiology ; Female ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Enzymologic ; Hospitals ; Humans ; Italy/epidemiology ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Phylogeny ; Rectum/microbiology ; Surgical Wound Infection/epidemiology/microbiology ; beta-Lactamases ; }, abstract = {We describe two multi drug-resistant (MDR) carbapenemase-producing Escherichia coli clinical isolates from an acute hospital in Milan. Both strains, isolated from a surgical wound sample and a surveillance rectal swab respectively, were positive for a blaNDM-type gene by Xpert Carba-R test. The whole-genome sequence characterization disclosed several resistance determinants: blaNDM-5, blaCMY-42, blaTEM-198, rmtB, mphA. The two isolates belonged to phylogenetic group A, sequence type (ST) 1702 and serotype O89:H9. PCR-based replicon typing and conjugation assay demonstrated an IncI1 plasmid localization for both blaNDM-5 and blaCMY-42 genes. This is the first report of a ST1702 NDM-5 and CMY-42- producing E. coli clone in Italy.}, } @article {pmid30028474, year = {2018}, author = {Salata, C and Lisotto, P and Boldrin, C and De Canale, E and Piccirillo, A and Calistri, A and Palù, G}, title = {A first molecular characterization of Listeria monocytogenes isolates circulating in humans from 2009 to 2014 in the Italian Veneto region.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {232-234}, pmid = {30028474}, issn = {1121-7138}, mesh = {Humans ; Italy/epidemiology ; Listeria monocytogenes/*classification ; Listeriosis/*epidemiology/*microbiology ; Retrospective Studies ; }, abstract = {Listeriosis is a disease usually associated with the consumption of low-processed ready-to-eat food products contaminated by Listeria monocytogenes. In Italy, listeriosis has an incidence of 0.19-0.27 cases per 100000 persons. Since detailed information concerning the molecular characterization of listeriosis in the Italian Veneto region is currently lacking, we analyzed 36 L. monocytogenes clinical isolates collected between 2009 and 2014. Results show that the serotype 1/2a was the most represented among the tested samples. No antimicrobial resistance was detected in selected isolates representing the main pulsotypes.}, } @article {pmid30028473, year = {2018}, author = {Gabanti, E and Lilleri, D and Scaramuzzi, L and Zelini, P and Rampino, T and Gerna, G}, title = {Comparison of the T-cell response to human cytomegalovirus (HCMV) as detected by cytokine flow cytometry and QuantiFERON-CMV assay in HCMV-seropositive kidney transplant recipients.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {195-202}, pmid = {30028473}, issn = {1121-7138}, mesh = {Adolescent ; Adult ; Aged ; Cytokines/*physiology ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/blood/*immunology ; Female ; Flow Cytometry ; Humans ; Immunity, Cellular ; Immunoassay/methods ; *Kidney Transplantation ; Male ; Middle Aged ; Sensitivity and Specificity ; T-Lymphocytes/*physiology ; *Transplant Recipients ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV)-specific T-cell response in kidney transplant recipients (KTR) helps to identify patients at risk for severe infection. To assess the T-cell response, this study compared our in-house developed reference test, based on T-cell (both CD4+ and CD8+) stimulation by autologous HCMV-infected dendritic cells (iDC) and subsequent detection by cytokine flow cytometry (CFC-iDC), with the Quanti-FERON-CMV (QF-CMV) assay. Fifty-three HCMV-seropositive KTR were enrolled. At the DNAemia peak, 33 (62%) had low viral load (LVL, <3x105 DNA copies/mL) self-resolving infection, 19 (36%) high viral load (HVL, >3x105 DNA copies/mL) infection treated with antivirals, and one LVL patient (2%) tissue-invasive disease alone. Both assays showed a delayed recovery of HCMV-specific T-cell immunity in HVL vs LVL patients. Immune reconstitution kinetics did not significantly differ between the two assays in HVL patients. QF-CMV and CFC-iDC showed comparable sensitivities, but QF-CMV had a lower (although not significantly) specificity. Indeed, 7/19 HVL patients (37%) were erroneously considered protected from severe infection by QF-CMV, whereas CFC-iDC misidentified only 3/19 (16%) patients as protected. Although our reference test takes longer to complete, it appears slightly better at predicting patients at risk for severe HCMV infection. Moreover, QF-CMV may provide false negative results with some HLA types.}, } @article {pmid30028290, year = {2018}, author = {Dong, C and Liu, R and Lai, Q and Liu, Y and Shao, Z}, title = {Thalassospira marina sp. nov., isolated from surface seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2943-2948}, doi = {10.1099/ijsem.0.002925}, pmid = {30028290}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodospirillaceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {Two novel marine bacteria, designated strains CSC3H3T and CSC1P2, were isolated from surface seawater of the South China Sea. Both strains were Gram-negative, oxidase-positive, catalase-positive, curved rods and motile. They grew at 10-40 °C, pH 5-10 and in the presence of 0-15 % (w/v) NaCl. Their 16S rRNA gene sequences were identical to each other. Phylogenetic analysis based on 16S rRNA gene sequences indicated that they belong to the genus Thalassospira, and shared 97.5-98.3 % sequence similarity to all other validly type strains of the genus Thalassospira, and the highest similarity was to the type strain Thalassospira povalilyticaZumi 95T (98.3 %), followed by Thalassospira australica NP3b2T (98.2 %). The digital DNA-DNA hybridization value between the two strains was 80.4 %, while the values with T. povalilyticaZumi 95T and T. australica NP3b2T were only 20.5-20.7 % and 20.4-20.5 %, respectively. The two strains possess similar major cellular fatty acids including C18 : 1ω7c, C16 : 0, C19 : 0ω8c cyclo, C18 : 1 2-OH and C17 : 0 cyclo. The G+C contents of the chromosomal DNA of strains CSC3H3T and CSC1P2 were 54.6 and 54.5 mol%, respectively. The major respiratory quinone was ubiquinone 10. Phosphatidylethanolamine, phosphatidylglycerol and several unidentified phospholipids, aminolipid and lipids were present in both strains. Based on phenotypic and genotypic characteristics, the two strains represent a novel species within the genus Thalassospira, for which the name Thalassospira marina sp. nov. is proposed. The type strain is CSC3H3T (=MCCC 1A11786T=KCTC 62333T).}, } @article {pmid30028289, year = {2018}, author = {Bourland, W and Rotterová, J and Čepička, I}, title = {Morphologic and molecular characterization of Brachonella pulchra (Kahl, 1927) comb. nov. (Armophorea, Ciliophora) with comments on cyst structure and formation.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3052-3065}, doi = {10.1099/ijsem.0.002888}, pmid = {30028289}, issn = {1466-5034}, mesh = {Ciliophora/*classification ; Microscopy, Electron, Scanning ; *Phylogeny ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA ; }, abstract = {In this article we provide morphologic and morphometric data based on in vivo observation, protargol impregnation, scanning electron microscopy and an 18S rRNA gene sequence for another member of the genus Brachonella, Brachonella pulchra comb. nov. (basionym: Metopus pulcher Kahl, 1927). We also provide preliminary data on resting cyst structure and formation in Brachonella pulchra and discuss the possible taxonomic usefulness of these structures.}, } @article {pmid30028288, year = {2018}, author = {Yuan, T and Liu, L and Huang, S and Taher, AH and Tan, Z and Wu, G and Peng, G}, title = {Rhizobium wuzhouense sp. nov., isolated from roots of Oryza officinalis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2918-2923}, doi = {10.1099/ijsem.0.002921}, pmid = {30028288}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Nucleic Acid Hybridization ; Oryza/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Rhizobium/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {Three bacterial isolates, designated W44T, W15 and W11, were isolated from the root of Oryza officinalis grown in Wuzhou, China. These isolates were Gram-negative, aerobic, motile and rod-shaped; demonstrated cellulase and urea activities; and formed cream-coloured colonies. The 16S rRNA gene sequence analysis indicated that the similarities between strain W44T and strains W15 and W11 were 100 %; all of them belonged to the genus Rhizobium and had the highest sequence similarity to Rhizobium rosettiformans W3T (98.7 %), followed by Rhizobium ipomoeae shin9-1T (98.2 %). Sequencing of housekeeping genes (recA, atpD, rpoB and glnA) of the novel isolates revealed similarities to members of established Rhizobium species to be less than 94.3 %. The values of DNA-DNA hybridization between strain W44T and the reference strains (R. rosettiformans W3T and R. ipomoeae shin9-1T) were 41.3 and 29.2 %, respectively. The major cellular fatty acid of strain W44T was summed feature 8 (C18 : 1ω9t and/or C18 : 1ω9c and/or C18 : 1ω7c). The polar lipid profile of strain W44T consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, two unidentified lipids and two unidentified aminophospholipids. The G+C content of strain W44T was 62.4 mol%. In nodulation tests, none of the three strains could induce nodule formation in Glycine max, Phaseolus vulgaris or Medicago sativa. The nodulation gene (nodA), nitrogenase reductase gene (nifH) and virulence gene (virC) were not detected by PCR in these strains. Based on the above results and phenotypic features, a novel species, Rhizobium wuzhouense sp. nov., is proposed, with strain W44T (=CCTCC AB 2017179T=GDMCC 1.1257T=KCTC 62194T) as the type strain.}, } @article {pmid30028287, year = {2018}, author = {Ohn, JE and Ten, LN and Kim, BO and Cho, YJ and Jung, HY}, title = {Hymenobacter rufus sp. nov., a bacterium isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2983-2989}, doi = {10.1099/ijsem.0.002934}, pmid = {30028287}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A bacterial strain, S1-2-2-6T, was isolated from a soil sample collected in Jeollabuk-do province, Republic of Korea. Cells of this strain were observed to be Gram-stain-negative, short and rod-shaped, and colonies were red to pink in colour. Analysis of 16S rRNA gene sequences identified this strain as representing a member of the genus Hymenobacter in the family Cytophagaceae, with the highest levels of sequence similarity being observed in relation to Hymenobacter terrae DG7AT (98.2 %), Hymenobacter rubidus DG7BT (97.9 %), Hymenobacter soli PB17T (97.7 %), and Hymenobacter daeguensis 16F3Y-2T (97.3 %). Growth of S1-2-2-6T was observed at 4-30 °C, pH 6-8 and in the presence of 0-0.5 % NaCl. The predominant respiratory quinone of this strain was menaquinone-7, the major fatty acids were C15 : 0 iso, C15 : 0 anteiso, and Summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), and the major polar lipid was phosphatidylethanolamine. The genomic DNA G+C content of S1-2-2-6T was 60.7 mol%. DNA-DNA hybridization experiments with H. terrae, H. rubidus, H. soli and H. daeguensisresulted in relatedness values of 35.9 and 38.4 %, 34.2 and 30.4 %, 28.3 and 33.1 %, and 23.5 and 27.9 %, respectively. These DNA-DNA hybridization results, in addition to some differentiating phenotypic properties, clearly indicate that S1-2-2-6T is a representative of a novel species of the genus Hymenobacter, for which the name Hymenobacter rufus sp. nov. is proposed. The type strain is S1-2-2-6T (=KCTC 52736T=JCM 32196T).}, } @article {pmid30028286, year = {2018}, author = {Park, YJ and Jeong, SE and Jung, HS and Park, SY and Jeon, CO}, title = {Nocardioides currus sp. nov., isolated from a mobile car air-conditioning system.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2977-2982}, doi = {10.1099/ijsem.0.002933}, pmid = {30028286}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; *Air Conditioning ; *Automobiles ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A strictly aerobic Gram-stain-positive bacterial strain, designated IB-3T, was isolated from a car air-conditioning system in the Republic of Korea. Cells were non-motile rods showing catalase- and oxidase-positive reactions. Growth of IB-3T was observed at 20-40 °C (optimum, 25 °C), at pH 6.5-9.0 (optimum, pH 7.5) and in the presence of 0-1 % (w/v) NaCl (optimum, 0 %). Menaquinone-8 (H4) was detected as the predominant respiratory quinone and iso-C16 : 0, 10-methyl-C17 : 0, iso-C17 : 0, C18 : 1ω9c, C17 : 1ω8c, C18 : 0, 10-methyl-C18 : 0 (TBSA) and C17 : 0 were identified as the major cellular fatty acids. Phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and phosphatidylinositol were detected as the major polar lipids. The major cell wall peptidoglycan type was ll-2,6-diaminopimelic acid. The G+C content of the genomic DNA was 71.5 mol%. IB-3T was most closely related to Nocardioides terrigenaDS-17T with a 98.0 % 16S rRNA gene sequence similarity. The results of phylogenetic analyses based on 16S rRNA gene sequences indicated that IB-3T formed a distinct phylogenetic lineage within the genus Nocardioidesof the family Nocardioidaceae. On the basis of the phenotypic, chemotaxonomic and molecular features, IB-3T represents a novel species of the genus Nocardioides, for which the name Nocardioidescurrus sp. nov. is proposed. The type strain is IB-3T (=KACC 19522T=JCM 32672T).}, } @article {pmid30028285, year = {2018}, author = {Yun, BR and Park, S and Kim, MK and Park, J and Kim, SB}, title = {Shewanella saliphila sp. nov., Shewanella ulleungensis sp. nov. and Shewanella litoralis sp. nov., isolated from coastal seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2960-2966}, doi = {10.1099/ijsem.0.002929}, pmid = {30028285}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Shewanella/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Three Gram-negative, non-spore-forming, rod-shaped and motile bacterial strains, designated MMS16-UL250T, MMS16-UL253T and MMS16-UL482T, were isolated from coastal seawater and subjected to taxonomic characterization. All isolates grew at 4-30 °C (optimum, 25 °C), at pH 6-10 (pH 7) and in the presence of up to 8 % NaCl (2.5-4.5 %). The 16S rRNA gene sequence similarities between the three isolates and Shewanella algicola St-6T, the closest species, were 98.1-99.2 %, and those among the isolates were 98.5-99.0 %. In the phylogenetic tree, MMS16-UL250T formed a cluster with S. algicola St-6T, but the DNA-DNA relatedness between the two strains was 28.8±1.5 %, thus confirming their separation at species level. The other two strains formed separate phylogenetic lines respectively. The main quinones for all strains were Q-7, Q-8, MK-7 and MMK-7, which is typical for Shewanella. The major polar lipids of all strains were phosphatidylglycerol and phosphatidylethanolamine, and the common major fatty acid was a summed feature consisting of C16 : 1ω7c and/or C16 : 1ω6c while the proportions varied among the three strains. The DNA G+C contents of the strains also varied between 42.1 and 43.7 mol%. Phenotypic properties distinguished each strain from S. algicola as well as from one another. Based on the polyphasic analysis, each strain is considered to represent a novel species of Shewanella, for which the names Shewanellasaliphila sp. nov. (type strain, MMS16-UL250T=KCTC 62131T=JCM 32304T), Shewanella ulleungensis sp. nov. (type strain, MMS16-UL253T=KCTC 62130T=JCM 32305T) and Shewanella litoralis sp. nov. (type strain, MMS16-UL482T=KCTC 62129T=JCM 32306T) are proposed.}, } @article {pmid30028284, year = {2018}, author = {Kämpfer, P and Glaeser, SP and Soby, SD}, title = {Chromobacterium pseudoviolaceum Kämpfer et al. 2009 is a later heterotypic synonym of Chromobacterium violaceum Bergonzini 1880.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2967-2968}, doi = {10.1099/ijsem.0.002930}, pmid = {30028284}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Chromobacterium/*classification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Published data on the genome sequences of Chromobacterium pseudoviolaceum LMG 3953T and Chromobacterium violaceum ATCC 12472T suggest that both isolates belong to the same species. Previous 16S rRNA gene sequence comparisons had demonstrated that these species share 99.9 % sequence similarity. Initial investigations of fatty acid patterns and substrate utilization had shown only a few differences between the type strains of both species. Despite the 47.5 % homology by DNA-DNA hybridization studies between these strains, in silico whole genome sequence comparisons have clearly demonstrated that OrthoANIu and Mash/MinHash values were >99.18 %. Molecular phylogeny based on the estimated phylogenetic positions of the published genome sequences of the two type strains, and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analyses indicate that these strains are members of the same species. Due to priority of publication and validation of names, Chromobacterium pseudoviolaceum is reclassified as Chromobacterium violaceum.}, } @article {pmid30028283, year = {2018}, author = {Dong, Y and Liu, Y and Chen, N and Zhong, Y and Liu, L and Xie, Q}, title = {Clostridium beihaiense sp. nov., an anaerobic bacterium isolated from activated sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2789-2793}, doi = {10.1099/ijsem.0.002885}, pmid = {30028283}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Clostridium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Waste Water/microbiology ; }, abstract = {A Gram-positive, strictly anaerobic, rod-shaped bacterium, designated YB-7T, was isolated from activated sludge of an anaerobic baffled reactor pond in Weizhou terminal wastewater treatment plant, Beihai, Guangxi, China. Strain YB-7T grew at pH 5.0-12.0 (optimum, pH 7.0), 20-45 °C (37 °C) and NaCl concentration of 0-5 % w/v (optimum, 5 %). 16S rRNA gene sequence analysis results showed that strain YB-7T belonged to the genus Clostridium and it was most closely related to Clostridium tetanomorphum DSM 4474T (96.9 % similarity). The DNA-DNA relatedness of strain YB-7T to Clostridium tetanomorphum DSM 4474T was 47.4 %. The DNA G+C content of strain YB-7T was determined to be 32.3 mol%, and the predominant cellar fatty acid (>10 %) was C16 : 0. Polar lipids of strain YB-7T included diphosphatidylglycerol, phosphatidylethylethanolamine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, two unidentified aminophospholipids, two unidentified phospholipids and unidentified lipids. The results of this study supported the conclusion that strain YB-7T should be assigned to a new member of the genus Clostridium, for which the name Clostridium beihaiense sp. nov. is proposed. The type strain is YB-7T (=CICC 24109T=KCTC 15555T).}, } @article {pmid30028282, year = {2018}, author = {Sultanpuram, VR and Mothe, T}, title = {Thalassorhabdus alkalitolerans gen. nov., sp. nov., a novel Bacillaceae member isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2969-2976}, doi = {10.1099/ijsem.0.002931}, pmid = {30028282}, issn = {1466-5034}, mesh = {Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; India ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phosphatidylglycerols/analysis ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-variable, rod-shaped, non-motile and non-endospore-forming bacterium (strain G27T) was isolated from near Dhuvaran, Gujarat, India. Based on 16S rRNA gene sequence analysis, strain G27T was identified as a member of the class Firmibacteria and was most closely related to Bacillus populi FJAT-45347T (94.9 % sequence similarity), Salipaludibacillus aurantiacus S9T (94.9 %), Salipaludibacillus neizhouensis KCTC 13187T (94.7 %), Alteribacillus iranensis DSM 23995T (94.6 %) and other Firmibacteria (<94.6 %). The DNA G+C content of strain G27T was 43.4±0.6 mol%. The cell-wall peptidoglycan contained meso-diaminopimelic acid. Polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and five unidentified lipids. The predominant isoprenoid quinone was menaquinone MK-7. Major fatty acids (>5 %) included anteiso-C15:0, iso-C15 : 0, anteiso-C17:0, C16 : 0 and iso-C16 : 0. The results of phylogenetic, chemotaxonomic and biochemical tests allowed the clear differentiation of strain G27T from all other members of the family Bacillaceae.It is therefore considered to represent a novel species of a new genus, for which the name Thalassorhabdus alkalitolerans gen. nov., sp. nov., is proposed. The type strain of Thalassorhabdus alkalitolerans is G27T (=MCC 3411T=CGMCC 1.15772T=KCTC 33941T).}, } @article {pmid30028281, year = {2018}, author = {Liao, H and Li, Y and Lin, X and Lai, Q and Tian, Y}, title = {Zhengella mangrovi gen. nov., sp. nov., a novel member of family Phyllobacteriaceae isolated from mangrove sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2819-2825}, doi = {10.1099/ijsem.0.002900}, pmid = {30028281}, issn = {1466-5034}, mesh = {Avicennia/*microbiology ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; Phyllobacteriaceae/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative strain, designed X9-2-2T, was isolated from mangrove sediment in Yunxiao Mangrove National Nature Reserve, China. Strain X9-2-2T showed less than 96.2 % 16S rRNA gene sequence similarity to type strains of species with validly published names. Phylogenetic analysis based on 16S rRNA gene sequences and rpoB protein sequences revealed that strain X9-2-2T formed a distinct monophyletic clade within the family Phyllobacteriaceae and clustered distantly with the genera Aliihoeflea, Phyllobacterium and Hoeflea. Cells of X9-2-2T were rod-shaped, motile with subpolar or lateral flagella and facultative anaerobic. Optimal growth occurred at 30-37 °C, at pH 7 and in the presence of 2 % NaCl. The DNA G+C content of strain X9-2-2T was 64.9 mol%. The major fatty acids were summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c 56.0 %), iso -C17 : 0 (9.1 %) and C12 : 0 (6.6 %). The predominant respiratory quinone was ubiquinone-10 and the major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmonomethylethanolamine, an unidentified aminolipid and two unidentified polar lipids. According to its morphology, physiology, fatty acid composition and 16S rRNA gene signature nucleotide patterns, strain X9-2-2T represents a novel species of a novel genus in the family Phyllobacteriaceae, for which the name Zhengella mangrovi gen. nov., sp. nov. is proposed. The type strain is X9-2-2T (=MCCC 1K03307T=JCM 32107T).}, } @article {pmid30028280, year = {2018}, author = {Wang, D and Xiang, Y and Jiang, C and Zhang, J and Hua, Z and Niu, L and Luo, L}, title = {Pueribacillus theae gen. nov., sp. nov., isolated from Pu'er tea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2878-2882}, doi = {10.1099/ijsem.0.002913}, pmid = {30028280}, issn = {1466-5034}, mesh = {Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; *Food Microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tea/*microbiology ; Vitamin K 2/chemistry ; }, abstract = {A novel bacterial strain, designated T8T, isolated from ripened Pu'er tea, was investigated by using a polyphasic taxonomic approach. Cells stained Gram-positive and were aerobic, sporogenous and rod-shaped with flagella. Phylogenetic analysis of 16S rRNA gene sequences revealed the strain belonged to the family Bacillaceae in the class Bacilli and represented an independent taxon separated from other genera. Strain T8T shared low levels of 16S rRNA gene sequence similarity (<94 %) to members of other genera in the family Bacillaceae and was most closely related to Bacillus composti SgZ-9T (93.3 % sequence similarity). The DNA G+C content of strain T8T was 40 mol%. The major fatty acids (>10 %) of strain T8T were iso-C15 : 0 and iso-C16 : 0. The strain had a cell-wall type A1γ peptidoglycan with meso-diaminopimelic acid as the diagnostic diamino acid. MK-7 (62 %), MK-6 (31 %) and MK-8 (7 %) were detected as the isoprenoid quinones. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmethylethanolamine and six unidentified phospholipids. On the basis of the polyphasic evidence presented, strain T8T is considered to represent a novel genus and species in the family Bacillaceae, for which we propose the name Pueribacillus theae gen. nov., sp. nov. The type strain is T8T (=CGMCC 1.15924T=KCTC 333888T).}, } @article {pmid30028279, year = {2018}, author = {Watanabe, M and Kojima, H and Fukui, M}, title = {Review of Desulfotomaculum species and proposal of the genera Desulfallas gen. nov., Desulfofundulus gen. nov., Desulfofarcimen gen. nov. and Desulfohalotomaculum gen. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2891-2899}, doi = {10.1099/ijsem.0.002915}, pmid = {30028279}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Desulfotomaculum/*classification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The genus Desulfotomaculumis a heterogeneous group of spore-forming sulfate-reducing bacteria. The type species of the genus is Desulfotomaculum nigrificans (Approved Lists 1980) emend. Visser et al. 2014. The results of phylogenetic analysis demonstrated that the genus Desulfotomaculum already has lost the clustering monophyly and was segregated into some distinct groups with low sequence similarity. Major features of the type strains in these groups were compared, and four novel genera, Desulfallas gen. nov., Desulfofundulus gen. nov., Desulfofarcimen gen. nov. and Desulfohalotomaculum gen. nov. were proposed to accommodate species transferred from the genus Desulfotomaculum.}, } @article {pmid30028082, year = {2018}, author = {Malard, LA and Pearce, DA}, title = {Microbial diversity and biogeography in Arctic soils.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {611-625}, doi = {10.1111/1758-2229.12680}, pmid = {30028082}, issn = {1758-2229}, support = {675546//Marie Curie/United Kingdom ; }, abstract = {Microorganisms dominate terrestrial environments in the polar regions and Arctic soils are known to harbour significant microbial diversity, far more diverse and numerous in the region than was once thought. Furthermore, the geographic distribution and structure of Arctic microbial communities remains elusive, despite their important roles in both biogeochemical cycling and in the generation and decomposition of climate active gases. Critically, Arctic soils are estimated to store over 1500 Pg of carbon and, thus, have the potential to generate positive feedback within the climate system. As the Arctic region is currently undergoing rapid change, the likelihood of faster release of greenhouse gases such as CO2 , CH4 and N2 O is increasing. Understanding the microbial communities in the region, in terms of their diversity, abundance and functional activity, is key to producing accurate models of greenhouse gas release. This review brings together existing data to determine what we know about microbial diversity and biogeography in Arctic soils.}, } @article {pmid30028074, year = {2018}, author = {Mühlenbruch, M and Grossart, HP and Eigemann, F and Voss, M}, title = {Mini-review: Phytoplankton-derived polysaccharides in the marine environment and their interactions with heterotrophic bacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2671-2685}, doi = {10.1111/1462-2920.14302}, pmid = {30028074}, issn = {1462-2920}, support = {RGP0020/2016//Human Frontier Science Program/ ; }, abstract = {Within the wealth of molecules constituting marine dissolved organic matter, carbohydrates make up the largest coherent and quantifiable fraction. Their main sources are from primary producers, which release large amounts of photosynthetic products - mainly polysaccharides - directly into the surrounding water via passive and active exudation. The organic carbon and other nutrients derived from these photosynthates enrich the 'phycosphere' and attract heterotrophic bacteria. The rapid uptake and remineralization of dissolved free monosaccharides by heterotrophic bacteria account for the barely detectable levels of these compounds. By contrast, dissolved combined polysaccharides can reach high concentrations, especially during phytoplankton blooms. Polysaccharides are too large to be taken up directly by heterotrophic bacteria, instead requiring hydrolytic cleavage to smaller oligo- or monomers by bacteria with a suitable set of exoenzymes. The release of diverse polysaccharides by various phytoplankton taxa is generally interpreted as the deposition of excess organic material. However, these molecules likely also fulfil distinct, yet not fully understood functions, as inferred from their active modulation in terms of quality and quantity when phytoplankton becomes nutrient limited or is exposed to heterotrophic bacteria. This minireview summarizes current knowledge regarding the exudation and composition of phytoplankton-derived exopolysaccharides and acquisition of these compounds by heterotrophic bacteria.}, } @article {pmid30026805, year = {2018}, author = {Gaggiotti, OE and Chao, A and Peres-Neto, P and Chiu, CH and Edwards, C and Fortin, MJ and Jost, L and Richards, CM and Selkoe, KA}, title = {Diversity from genes to ecosystems: A unifying framework to study variation across biological metrics and scales.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1176-1193}, pmid = {30026805}, issn = {1752-4571}, abstract = {Biological diversity is a key concept in the life sciences and plays a fundamental role in many ecological and evolutionary processes. Although biodiversity is inherently a hierarchical concept covering different levels of organization (genes, population, species, ecological communities and ecosystems), a diversity index that behaves consistently across these different levels has so far been lacking, hindering the development of truly integrative biodiversity studies. To fill this important knowledge gap, we present a unifying framework for the measurement of biodiversity across hierarchical levels of organization. Our weighted, information-based decomposition framework is based on a Hill number of order q = 1, which weights all elements in proportion to their frequency and leads to diversity measures based on Shannon's entropy. We investigated the numerical behaviour of our approach with simulations and showed that it can accurately describe complex spatial hierarchical structures. To demonstrate the intuitive and straightforward interpretation of our diversity measures in terms of effective number of components (alleles, species, etc.), we applied the framework to a real data set on coral reef biodiversity. We expect our framework will have multiple applications covering the fields of conservation biology, community genetics and eco-evolutionary dynamics.}, } @article {pmid30026804, year = {2018}, author = {Pierson, JC and Graves, TA and Banks, SC and Kendall, KC and Lindenmayer, DB}, title = {Relationship between effective and demographic population size in continuously distributed populations.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1162-1175}, pmid = {30026804}, issn = {1752-4571}, abstract = {Genetic monitoring of wild populations can offer insights into demographic and genetic information simultaneously. However, widespread application of genetic monitoring is hindered by large uncertainty in the estimation and interpretation of target metrics such as contemporary effective population size, Ne . We used four long-term genetic and demographic studies (≥9 years) to evaluate the temporal stability of the relationship between Ne and demographic population size (Nc). These case studies focused on mammals that are continuously distributed, yet dispersal-limited within the spatial scale of the study. We estimated local, contemporary Ne with single-sample methods (LDNE, Heterozygosity Excess, and Molecular Ancestry) and demographic abundance with either mark-recapture estimates or catch-per-unit effort indices. Estimates of Ne varied widely within each case study suggesting interpretation of estimates is challenging. We found inconsistent correlations and trends both among estimates of Ne and between Ne and Nc suggesting the value of Ne as an indicator of Nc is limited in some cases. In the two case studies with consistent trends between Ne and Nc , FIS was more stable over time and lower, suggesting FIS may be a good indicator that the population was sampled at a spatial scale at which genetic structure is not biasing estimates of Ne . These results suggest that more empirical work on the estimation of Ne in continuous populations is needed to understand the appropriate context to use LDNe as a useful metric in a monitoring programme to detect temporal trends in either Ne or Nc .}, } @article {pmid30026803, year = {2018}, author = {Milligan, BG and Archer, FI and Ferchaud, AL and Hand, BK and Kierepka, EM and Waples, RS}, title = {Disentangling genetic structure for genetic monitoring of complex populations.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1149-1161}, pmid = {30026803}, issn = {1752-4571}, abstract = {Genetic monitoring estimates temporal changes in population parameters from molecular marker information. Most populations are complex in structure and change through time by expanding or contracting their geographic range, becoming fragmented or coalescing, or increasing or decreasing density. Traditional approaches to genetic monitoring rely on quantifying temporal shifts of specific population metrics-heterozygosity, numbers of alleles, effective population size-or measures of geographic differentiation such as FST. However, the accuracy and precision of the results can be heavily influenced by the type of genetic marker used and how closely they adhere to analytical assumptions. Care must be taken to ensure that inferences reflect actual population processes rather than changing molecular techniques or incorrect assumptions of an underlying model of population structure. In many species of conservation concern, true population structure is unknown, or structure might shift over time. In these cases, metrics based on inappropriate assumptions of population structure may not provide quality information regarding the monitored population. Thus, we need an inference model that decouples the complex elements that define population structure from estimation of population parameters of interest and reveals, rather than assumes, fine details of population structure. Encompassing a broad range of possible population structures would enable comparable inferences across biological systems, even in the face of range expansion or contraction, fragmentation, or changes in density. Currently, the best candidate is the spatial Λ-Fleming-Viot (SLFV) model, a spatially explicit individually based coalescent model that allows independent inference of two of the most important elements of population structure: local population density and local dispersal. We support increased use of the SLFV model for genetic monitoring by highlighting its benefits over traditional approaches. We also discuss necessary future directions for model development to support large genomic datasets informing real-world management and conservation issues.}, } @article {pmid30026802, year = {2018}, author = {Jost, L and Archer, F and Flanagan, S and Gaggiotti, O and Hoban, S and Latch, E}, title = {Differentiation measures for conservation genetics.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1139-1148}, pmid = {30026802}, issn = {1752-4571}, abstract = {We compare the two main classes of measures of population structure in genetics: (i) fixation measures such as FST,GST, and θ and (ii) allelic differentiation measures such as Jost's D and entropy differentiation. These two groups of measures quantify complementary aspects of population structure, which have no necessary relationship with each other. We focus especially on empirical aspects of population structure relevant to conservation analyses. At the empirical level, the first set of measures quantify nearness to fixation, while the second set of measures quantify relative degree of allelic differentiation. The two sets of measures do not compete with each other. Fixation measures are often misinterpreted as measures of allelic differentiation in conservation applications; we give examples and theoretical explanations showing why this interpretation can mislead. This misinterpretation has led to the mistaken belief that the absolute number of migrants determines allelic differentiation between demes when mutation rate is low; we show that in the finite island model, the absolute number of migrants determines nearness to fixation, not allelic differentiation. We show that a different quantity, the factor that controls Jost's D, is a good predictor of the evolution of the actual genetic divergence between demes at equilibrium in this model. We also show that when conservation decisions require judgments about differences in genetic composition between demes, allelic differentiation measures should be used instead of fixation measures. Allelic differentiation of fast-mutating markers can be used to rank pairs or sets of demes according to their differentiation, but the allelic differentiation at coding loci of interest should be directly measured in order to judge its actual magnitude at these loci.}, } @article {pmid30026801, year = {2018}, author = {Swift, JF and Lance, RF and Guan, X and Britzke, ER and Lindsay, DL and Edwards, CE}, title = {Multifaceted DNA metabarcoding: Validation of a noninvasive, next-generation approach to studying bat populations.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1120-1138}, pmid = {30026801}, issn = {1752-4571}, abstract = {As multiple species of bats are currently experiencing dramatic declines in populations due to white-nose syndrome (WNS) and other factors, conservation managers have an urgent need for data on the ecology and overall status of populations of once-common bat species. Standard approaches to obtain data on bat populations often involve capture and handling, requiring extensive expertise and unavoidably resulting in stress to the bats. New methods to rapidly obtain critical data are needed that minimize both the stress on bats and the spread of WNS. Guano provides a noninvasive source of DNA that includes information from the bat, but also dietary items, parasites, and pathogens. DNA metabarcoding is a high-throughput, DNA-based identification technique to assess the biodiversity of environmental or fecal samples. We investigated the use of multifaceted DNA metabarcoding (MDM), a technique combining next-generation DNA sequencing (NGS), DNA barcodes, and bioinformatic analysis, to simultaneously collect data on multiple parameters of interest (bat species composition, individual genotype, sex ratios, diet, parasites, and presence of WNS) from fecal samples using a single NGS run. We tested the accuracy of each MDM assay using samples in which these parameters were previously determined using conventional approaches. We found that assays for bat species identification, insect diet, parasite diversity, and genotype were both sensitive and accurate, the assay to detect WNS was highly sensitive but requires careful sample processing steps to ensure the reliability of results, while assays for nectivorous diet and sex showed lower sensitivity. MDM was able to quantify multiple data classes from fecal samples simultaneously, and results were consistent whether we included assays for a single data class or multiple data classes. Overall, MDM is a useful approach that employs noninvasive sampling and a customizable suite of assays to gain important and largely accurate information on bat ecology and population dynamics.}, } @article {pmid30026800, year = {2018}, author = {Carroll, EL and Bruford, MW and DeWoody, JA and Leroy, G and Strand, A and Waits, L and Wang, J}, title = {Genetic and genomic monitoring with minimally invasive sampling methods.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1094-1119}, pmid = {30026800}, issn = {1752-4571}, abstract = {The decreasing cost and increasing scope and power of emerging genomic technologies are reshaping the field of molecular ecology. However, many modern genomic approaches (e.g., RAD-seq) require large amounts of high-quality template DNA. This poses a problem for an active branch of conservation biology: genetic monitoring using minimally invasive sampling (MIS) methods. Without handling or even observing an animal, MIS methods (e.g., collection of hair, skin, faeces) can provide genetic information on individuals or populations. Such samples typically yield low-quality and/or quantities of DNA, restricting the type of molecular methods that can be used. Despite this limitation, genetic monitoring using MIS is an effective tool for estimating population demographic parameters and monitoring genetic diversity in natural populations. Genetic monitoring is likely to become more important in the future as many natural populations are undergoing anthropogenically driven declines, which are unlikely to abate without intensive adaptive management efforts that often include MIS approaches. Here, we profile the expanding suite of genomic methods and platforms compatible with producing genotypes from MIS, considering factors such as development costs and error rates. We evaluate how powerful new approaches will enhance our ability to investigate questions typically answered using genetic monitoring, such as estimating abundance, genetic structure and relatedness. As the field is in a period of unusually rapid transition, we also highlight the importance of legacy data sets and recommend how to address the challenges of moving between traditional and next-generation genetic monitoring platforms. Finally, we consider how genetic monitoring could move beyond genotypes in the future. For example, assessing microbiomes or epigenetic markers could provide a greater understanding of the relationship between individuals and their environment.}, } @article {pmid30026799, year = {2018}, author = {Gaughran, SJ and Quinzin, MC and Miller, JM and Garrick, RC and Edwards, DL and Russello, MA and Poulakakis, N and Ciofi, C and Beheregaray, LB and Caccone, A}, title = {Theory, practice, and conservation in the age of genomics: The Galápagos giant tortoise as a case study.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1084-1093}, pmid = {30026799}, issn = {1752-4571}, support = {S10 RR019895/RR/NCRR NIH HHS/United States ; S10 RR029676/RR/NCRR NIH HHS/United States ; }, abstract = {High-throughput DNA sequencing allows efficient discovery of thousands of single nucleotide polymorphisms (SNPs) in nonmodel species. Population genetic theory predicts that this large number of independent markers should provide detailed insights into population structure, even when only a few individuals are sampled. Still, sampling design can have a strong impact on such inferences. Here, we use simulations and empirical SNP data to investigate the impacts of sampling design on estimating genetic differentiation among populations that represent three species of Galápagos giant tortoises (Chelonoidis spp.). Though microsatellite and mitochondrial DNA analyses have supported the distinctiveness of these species, a recent study called into question how well these markers matched with data from genomic SNPs, thereby questioning decades of studies in nonmodel organisms. Using >20,000 genomewide SNPs from 30 individuals from three Galápagos giant tortoise species, we find distinct structure that matches the relationships described by the traditional genetic markers. Furthermore, we confirm that accurate estimates of genetic differentiation in highly structured natural populations can be obtained using thousands of SNPs and 2-5 individuals, or hundreds of SNPs and 10 individuals, but only if the units of analysis are delineated in a way that is consistent with evolutionary history. We show that the lack of structure in the recent SNP-based study was likely due to unnatural grouping of individuals and erroneous genotype filtering. Our study demonstrates that genomic data enable patterns of genetic differentiation among populations to be elucidated even with few samples per population, and underscores the importance of sampling design. These results have specific implications for studies of population structure in endangered species and subsequent management decisions.}, } @article {pmid30026798, year = {2018}, author = {Leroy, G and Carroll, EL and Bruford, MW and DeWoody, JA and Strand, A and Waits, L and Wang, J}, title = {Next-generation metrics for monitoring genetic erosion within populations of conservation concern.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1066-1083}, pmid = {30026798}, issn = {1752-4571}, abstract = {Genetic erosion is a major threat to biodiversity because it can reduce fitness and ultimately contribute to the extinction of populations. Here, we explore the use of quantitative metrics to detect and monitor genetic erosion. Monitoring systems should not only characterize the mechanisms and drivers of genetic erosion (inbreeding, genetic drift, demographic instability, population fragmentation, introgressive hybridization, selection) but also its consequences (inbreeding and outbreeding depression, emergence of large-effect detrimental alleles, maladaptation and loss of adaptability). Technological advances in genomics now allow the production of data the can be measured by new metrics with improved precision, increased efficiency and the potential to discriminate between neutral diversity (shaped mainly by population size and gene flow) and functional/adaptive diversity (shaped mainly by selection), allowing the assessment of management-relevant genetic markers. The requirements of such studies in terms of sample size and marker density largely depend on the kind of population monitored, the questions to be answered and the metrics employed. We discuss prospects for the integration of this new information and metrics into conservation monitoring programmes.}, } @article {pmid30026797, year = {2018}, author = {Ferchaud, AL and Laporte, M and Perrier, C and Bernatchez, L}, title = {Impact of supplementation on deleterious mutation distribution in an exploited salmonid.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1053-1065}, pmid = {30026797}, issn = {1752-4571}, abstract = {Deleterious mutations have important implications for the evolutionary trajectories of populations. While several studies recently investigated the dynamics of deleterious mutations in wild populations, no study has yet explored the fate of deleterious mutations in a context of populations managed by supplementation. Here, based on a dataset of nine wild and 15 supplemented Lake Trout populations genotyped at 4,982 single nucleotide polymorphisms (SNP)s by means of genotype by sequencing (GBS), we explored the effect of supplementation on the frequency of putatively deleterious variants. Three main findings are consequential for the management of fish populations. First, an increase in neutral genetic diversity in stocked populations compared with unstocked ones was observed. Second, putatively deleterious mutations were more likely to be found in unstocked than in stocked populations, suggesting a lower efficiency to purge deleterious mutations in unstocked lakes. Third, a population currently used as a major source for supplementation is characterized by several fixed putatively deleterious alleles. Therefore, other source populations with lower abundance of putatively deleterious mutations should be favored as sources of supplementation. We discuss management implications of our results, especially pertaining to the joint identification of neutral and deleterious mutations that could help refining the choice of source and sink populations for supplementation in order to maximize their evolutionary potential and to limit their mutation load.}, } @article {pmid30026796, year = {2018}, author = {Flanagan, SP and Forester, BR and Latch, EK and Aitken, SN and Hoban, S}, title = {Guidelines for planning genomic assessment and monitoring of locally adaptive variation to inform species conservation.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1035-1052}, pmid = {30026796}, issn = {1752-4571}, abstract = {Identifying and monitoring locally adaptive genetic variation can have direct utility for conserving species at risk, especially when management may include actions such as translocations for restoration, genetic rescue, or assisted gene flow. However, genomic studies of local adaptation require careful planning to be successful, and in some cases may not be a worthwhile use of resources. Here, we offer an adaptive management framework to help conservation biologists and managers decide when genomics is likely to be effective in detecting local adaptation, and how to plan assessment and monitoring of adaptive variation to address conservation objectives. Studies of adaptive variation using genomic tools will inform conservation actions in many cases, including applications such as assisted gene flow and identifying conservation units. In others, assessing genetic diversity, inbreeding, and demographics using selectively neutral genetic markers may be most useful. And in some cases, local adaptation may be assessed more efficiently using alternative approaches such as common garden experiments. Here, we identify key considerations of genomics studies of locally adaptive variation, provide a road map for successful collaborations with genomics experts including key issues for study design and data analysis, and offer guidelines for interpreting and using results from genomic assessments to inform monitoring programs and conservation actions.}, } @article {pmid30026795, year = {2018}, author = {Hunter, ME and Hoban, SM and Bruford, MW and Segelbacher, G and Bernatchez, L}, title = {Next-generation conservation genetics and biodiversity monitoring.}, journal = {Evolutionary applications}, volume = {11}, number = {7}, pages = {1029-1034}, pmid = {30026795}, issn = {1752-4571}, abstract = {This special issue of Evolutionary Applications consists of 10 publications investigating the use of next-generation tools and techniques in population genetic analyses and biodiversity assessment. The special issue stems from a 2016 Next Generation Genetic Monitoring Workshop, hosted by the National Institute for Mathematical and Biological Synthesis (NIMBioS) in Tennessee, USA. The improved accessibility of next-generation sequencing platforms has allowed molecular ecologists to rapidly produce large amounts of data. However, with the increased availability of new genomic markers and mathematical techniques, care is needed in selecting appropriate study designs, interpreting results in light of conservation concerns, and determining appropriate management actions. This special issue identifies key attributes of successful genetic data analyses in biodiversity evaluation and suggests ways to improve analyses and their application in current population and conservation genetics research.}, } @article {pmid30026520, year = {2018}, author = {Du Toit, A}, title = {Defence countermeasures.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {520}, doi = {10.1038/s41579-018-0063-7}, pmid = {30026520}, issn = {1740-1534}, } @article {pmid30026319, year = {2018}, author = {Yuter, SE and Hader, JD and Miller, MA and Mechem, DB}, title = {Abrupt cloud clearing of marine stratocumulus in the subtropical southeast Atlantic.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {697-701}, doi = {10.1126/science.aar5836}, pmid = {30026319}, issn = {1095-9203}, abstract = {We document rapid and abrupt clearings of large portions of the subtropical marine low cloud deck that have implications for the global radiation balance and climate sensitivity. Over the southeast Atlantic, large areas of stratocumulus are quickly eroded, yielding partial or complete clearing along sharp transitions hundreds to thousands of kilometers in length that move westward at 8 to 12 meters per second and travel as far as 1000+ kilometers from the African coast. The westward-moving cloudiness reductions have an annual peak in occurrence in the period from April through June. The cloud erosion boundaries reduce cloud at ≈10-kilometer scale in less than 15 minutes, move approximately perpendicular to the mean flow, and are often accompanied by small-scale wave features. Observations suggest that the cloud erosion is caused by atmospheric gravity waves.}, } @article {pmid30026318, year = {2018}, author = {Tsesses, S and Ostrovsky, E and Cohen, K and Gjonaj, B and Lindner, NH and Bartal, G}, title = {Optical skyrmion lattice in evanescent electromagnetic fields.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6406}, pages = {993-996}, doi = {10.1126/science.aau0227}, pmid = {30026318}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Topological defects play a key role in a variety of physical systems, ranging from high-energy to solid-state physics. A skyrmion is a type of topological defect that has shown promise for applications in the fields of magnetic storage and spintronics. We show that optical skyrmion lattices can be generated using evanescent electromagnetic fields and demonstrate this using surface plasmon polaritons, imaged by phase-resolved near-field optical microscopy. We show how the optical skyrmion lattice exhibits robustness to imperfections while the topological domain walls in the lattice can be continuously tuned, changing the spatial structure of the skyrmions from bubble type to Néel type. Extending the generation of skyrmions to photonic systems provides various possibilities for applications in optical information processing, transfer, and storage.}, } @article {pmid30026317, year = {2018}, author = {Lim, J and Kim, D and Lee, YS and Ha, M and Lee, M and Yeo, J and Chang, H and Song, J and Ahn, K and Kim, VN}, title = {Mixed tailing by TENT4A and TENT4B shields mRNA from rapid deadenylation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {701-704}, doi = {10.1126/science.aam5794}, pmid = {30026317}, issn = {1095-9203}, mesh = {Chromosomal Proteins, Non-Histone/genetics/*metabolism ; DNA-Directed DNA Polymerase/genetics/*metabolism ; Exoribonucleases/metabolism ; Fibroblasts ; Gene Deletion ; *Gene Expression Regulation ; Gene Knockout Techniques ; HEK293 Cells ; HeLa Cells ; Humans ; *RNA 3' End Processing ; RNA Nucleotidyltransferases/genetics/*metabolism ; RNA, Messenger/*metabolism ; }, abstract = {RNA tails play integral roles in the regulation of messenger RNA (mRNA) translation and decay. Guanylation of the poly(A) tail was discovered recently, yet the enzymology and function remain obscure. Here we identify TENT4A (PAPD7) and TENT4B (PAPD5) as the enzymes responsible for mRNA guanylation. Purified TENT4 proteins generate a mixed poly(A) tail with intermittent non-adenosine residues, the most common of which is guanosine. A single guanosine residue is sufficient to impede the deadenylase CCR4-NOT complex, which trims the tail and exposes guanosine at the 3' end. Consistently, depletion of TENT4A and TENT4B leads to a decrease in mRNA half-life and abundance in cells. Thus, TENT4A and TENT4B produce a mixed tail that shields mRNA from rapid deadenylation. Our study unveils the role of mixed tailing and expands the complexity of posttranscriptional gene regulation.}, } @article {pmid30026316, year = {2018}, author = {Cuchet-Lourenço, D and Eletto, D and Wu, C and Plagnol, V and Papapietro, O and Curtis, J and Ceron-Gutierrez, L and Bacon, CM and Hackett, S and Alsaleem, B and Maes, M and Gaspar, M and Alisaac, A and Goss, E and AlIdrissi, E and Siegmund, D and Wajant, H and Kumararatne, D and AlZahrani, MS and Arkwright, PD and Abinun, M and Doffinger, R and Nejentsev, S}, title = {Biallelic RIPK1 mutations in humans cause severe immunodeficiency, arthritis, and intestinal inflammation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {810-813}, doi = {10.1126/science.aar2641}, pmid = {30026316}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Alleles ; Arthritis/*genetics/immunology ; Cytokines/metabolism ; Female ; Fibroblasts/metabolism/pathology ; Humans ; Inflammatory Bowel Diseases/*genetics/immunology ; Lymphopenia/genetics ; Male ; Mitogen-Activated Protein Kinases/metabolism ; Pedigree ; Receptor-Interacting Protein Serine-Threonine Kinases/*genetics ; Severe Combined Immunodeficiency/*genetics/immunology ; }, abstract = {RIPK1 (receptor-interacting serine/threonine kinase 1) is a master regulator of signaling pathways leading to inflammation and cell death and is of medical interest as a drug target. We report four patients from three unrelated families with complete RIPK1 deficiency caused by rare homozygous mutations. The patients suffered from recurrent infections, early-onset inflammatory bowel disease, and progressive polyarthritis. They had immunodeficiency with lymphopenia and altered production of various cytokines revealed by whole-blood assays. In vitro, RIPK1-deficient cells showed impaired mitogen-activated protein kinase activation and cytokine secretion and were prone to necroptosis. Hematopoietic stem cell transplantation reversed cytokine production defects and resolved clinical symptoms in one patient. Thus, RIPK1 plays a critical role in the human immune system.}, } @article {pmid30026315, year = {2018}, author = {Yao, W and Paytan, A and Wortmann, UG}, title = {Large-scale ocean deoxygenation during the Paleocene-Eocene Thermal Maximum.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {804-806}, doi = {10.1126/science.aar8658}, pmid = {30026315}, issn = {1095-9203}, mesh = {*Aquatic Organisms ; Carbon Cycle ; Hydrogen Sulfide/*toxicity ; Models, Theoretical ; Oceans and Seas ; Oxygen/analysis/*metabolism ; }, abstract = {The consequences of global warming for fisheries are not well understood, but the geological record demonstrates that carbon cycle perturbations are frequently associated with ocean deoxygenation. Of particular interest is the Paleocene-Eocene Thermal Maximum (PETM), where the carbon dioxide input into the atmosphere was similar to the IPCC RCP8.5 emission scenario. Here we present sulfur-isotope data that record a positive 1 per mil excursion during the PETM. Modeling suggests that large parts of the ocean must have become sulfidic. The toxicity of hydrogen sulfide will render two of the largest and least explored ecosystems on Earth, the mesopelagic and bathypelagic zones, uninhabitable by multicellular organisms. This will affect many marine species whose ecozones stretch into the deep ocean.}, } @article {pmid30026314, year = {2018}, author = {Eubelen, M and Bostaille, N and Cabochette, P and Gauquier, A and Tebabi, P and Dumitru, AC and Koehler, M and Gut, P and Alsteens, D and Stainier, DYR and Garcia-Pino, A and Vanhollebeke, B}, title = {A molecular mechanism for Wnt ligand-specific signaling.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {}, doi = {10.1126/science.aat1178}, pmid = {30026314}, issn = {1095-9203}, mesh = {Animals ; Brain/blood supply/cytology ; Dishevelled Proteins/*metabolism ; Endothelial Cells/metabolism ; Frizzled Receptors/*metabolism ; HEK293 Cells ; Humans ; Ligands ; Neovascularization, Physiologic ; Protein Binding ; Receptors, G-Protein-Coupled/*metabolism ; Wnt Proteins/*metabolism ; *Wnt Signaling Pathway ; Zebrafish ; }, abstract = {Wnt signaling is key to many developmental, physiological, and disease processes in which cells seem able to discriminate between multiple Wnt ligands. This selective Wnt recognition or "decoding" capacity has remained enigmatic because Wnt/Frizzled interactions are largely incompatible with monospecific recognition. Gpr124 and Reck enable brain endothelial cells to selectively respond to Wnt7. We show that Reck binds with low micromolar affinity to the intrinsically disordered linker region of Wnt7. Availability of Reck-bound Wnt7 for Frizzled signaling relies on the interaction between Gpr124 and Dishevelled. Through polymerization, Dishevelled recruits Gpr124 and the associated Reck-bound Wnt7 into dynamic Wnt/Frizzled/Lrp5/6 signalosomes, resulting in increased local concentrations of Wnt7 available for Frizzled signaling. This work provides mechanistic insights into the Wnt decoding capacities of vertebrate cells and unravels structural determinants of the functional diversification of Wnt family members.}, } @article {pmid30026229, year = {2018}, author = {Pradhan, D}, title = {Working science into fundraising.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {302}, doi = {10.1126/science.361.6399.302}, pmid = {30026229}, issn = {1095-9203}, } @article {pmid30026228, year = {2018}, author = {Zhang, J and Wu, T and Simon, J and Takada, M and Saito, R and Fan, C and Liu, XD and Jonasch, E and Xie, L and Chen, X and Yao, X and Teh, BT and Tan, P and Zheng, X and Li, M and Lawrence, C and Fan, J and Geng, J and Liu, X and Hu, L and Wang, J and Liao, C and Hong, K and Zurlo, G and Parker, JS and Auman, JT and Perou, CM and Rathmell, WK and Kim, WY and Kirschner, MW and Kaelin, WG and Baldwin, AS and Zhang, Q}, title = {VHL substrate transcription factor ZHX2 as an oncogenic driver in clear cell renal cell carcinoma.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {290-295}, pmid = {30026228}, issn = {1095-9203}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R35 CA197684/CA/NCI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R21 CA223675/CA/NCI NIH HHS/United States ; R01 CA211732/CA/NCI NIH HHS/United States ; R35 CA210068/CA/NCI NIH HHS/United States ; P30 NS045892/NS/NINDS NIH HHS/United States ; R00 CA160351/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Renal Cell/drug therapy/*genetics ; Chromatin Immunoprecipitation ; Female ; Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/*metabolism ; Humans ; Hydroxylation ; Kidney Neoplasms/drug therapy/*genetics ; Mice ; Mice, SCID ; Molecular Targeted Therapy ; Mutation ; NF-kappa B/metabolism ; *Oncogenes ; Substrate Specificity ; Transcription Factors/genetics/*metabolism ; Von Hippel-Lindau Tumor Suppressor Protein/genetics/*metabolism ; }, abstract = {Inactivation of the von Hippel-Lindau (VHL) E3 ubiquitin ligase protein is a hallmark of clear cell renal cell carcinoma (ccRCC). Identifying how pathways affected by VHL loss contribute to ccRCC remains challenging. We used a genome-wide in vitro expression strategy to identify proteins that bind VHL when hydroxylated. Zinc fingers and homeoboxes 2 (ZHX2) was found as a VHL target, and its hydroxylation allowed VHL to regulate its protein stability. Tumor cells from ccRCC patients with VHL loss-of-function mutations usually had increased abundance and nuclear localization of ZHX2. Functionally, depletion of ZHX2 inhibited VHL-deficient ccRCC cell growth in vitro and in vivo. Mechanistically, integrated chromatin immunoprecipitation sequencing and microarray analysis showed that ZHX2 promoted nuclear factor κB activation. These studies reveal ZHX2 as a potential therapeutic target for ccRCC.}, } @article {pmid30026227, year = {2018}, author = {Grevet, JD and Lan, X and Hamagami, N and Edwards, CR and Sankaranarayanan, L and Ji, X and Bhardwaj, SK and Face, CJ and Posocco, DF and Abdulmalik, O and Keller, CA and Giardine, B and Sidoli, S and Garcia, BA and Chou, ST and Liebhaber, SA and Hardison, RC and Shi, J and Blobel, GA}, title = {Domain-focused CRISPR screen identifies HRI as a fetal hemoglobin regulator in human erythroid cells.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {285-290}, pmid = {30026227}, issn = {1095-9203}, support = {F30 DK107055/DK/NIDDK NIH HHS/United States ; R01 HL065449/HL/NHLBI NIH HHS/United States ; R56 DK065806/DK/NIDDK NIH HHS/United States ; R01 HL119479/HL/NHLBI NIH HHS/United States ; T32 GM008216/GM/NIGMS NIH HHS/United States ; R37 DK058044/DK/NIDDK NIH HHS/United States ; R01 AI118891/AI/NIAID NIH HHS/United States ; R01 DK054937/DK/NIDDK NIH HHS/United States ; R01 GM110174/GM/NIGMS NIH HHS/United States ; R24 DK106766/DK/NIDDK NIH HHS/United States ; R01 MD009124/MD/NIMHD NIH HHS/United States ; U54 HG006998/HG/NHGRI NIH HHS/United States ; }, mesh = {Anemia, Sickle Cell/drug therapy/*genetics ; CRISPR-Cas Systems ; Carrier Proteins/*genetics/metabolism ; Cell Line ; Erythroid Cells/*metabolism ; Fetal Hemoglobin/*genetics ; *Gene Expression Regulation ; Genetic Testing ; Humans ; Molecular Targeted Therapy ; Nuclear Proteins/*genetics/metabolism ; RNA, Guide ; eIF-2 Kinase/*genetics/metabolism ; }, abstract = {Increasing fetal hemoglobin (HbF) levels in adult red blood cells provides clinical benefit to patients with sickle cell disease and some forms of β-thalassemia. To identify potentially druggable HbF regulators in adult human erythroid cells, we employed a protein kinase domain-focused CRISPR-Cas9-based genetic screen with a newly optimized single-guide RNA scaffold. The screen uncovered the heme-regulated inhibitor HRI (also known as EIF2AK1), an erythroid-specific kinase that controls protein translation, as an HbF repressor. HRI depletion markedly increased HbF production in a specific manner and reduced sickling in cultured erythroid cells. Diminished expression of the HbF repressor BCL11A accounted in large part for the effects of HRI depletion. Taken together, these results suggest HRI as a potential therapeutic target for hemoglobinopathies.}, } @article {pmid30026226, year = {2018}, author = {Rocha, LA and Pinheiro, HT and Shepherd, B and Papastamatiou, YP and Luiz, OJ and Pyle, RL and Bongaerts, P}, title = {Mesophotic coral ecosystems are threatened and ecologically distinct from shallow water reefs.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {281-284}, doi = {10.1126/science.aaq1614}, pmid = {30026226}, issn = {1095-9203}, mesh = {Animals ; *Anthozoa ; *Biodiversity ; *Conservation of Natural Resources ; *Coral Reefs ; Seawater ; }, abstract = {The rapid degradation of coral reefs is one of the most serious biodiversity problems facing our generation. Mesophotic coral reefs (at depths of 30 to 150 meters) have been widely hypothesized to provide refuge from natural and anthropogenic impacts, a promise for the survival of shallow reefs. The potential role of mesophotic reefs as universal refuges is often highlighted in reef conservation research. This hypothesis rests on two assumptions: (i) that there is considerable overlap in species composition and connectivity between shallow and deep populations and (ii) that deep reefs are less susceptible to anthropogenic and natural impacts than their shallower counterparts. Here we present evidence contradicting these assumptions and argue that mesophotic reefs are distinct, impacted, and in as much need of protection as shallow coral reefs.}, } @article {pmid30026225, year = {2018}, author = {Yao, L and Garmash, O and Bianchi, F and Zheng, J and Yan, C and Kontkanen, J and Junninen, H and Mazon, SB and Ehn, M and Paasonen, P and Sipilä, M and Wang, M and Wang, X and Xiao, S and Chen, H and Lu, Y and Zhang, B and Wang, D and Fu, Q and Geng, F and Li, L and Wang, H and Qiao, L and Yang, X and Chen, J and Kerminen, VM and Petäjä, T and Worsnop, DR and Kulmala, M and Wang, L}, title = {Atmospheric new particle formation from sulfuric acid and amines in a Chinese megacity.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {278-281}, doi = {10.1126/science.aao4839}, pmid = {30026225}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Atmospheric new particle formation (NPF) is an important global phenomenon that is nevertheless sensitive to ambient conditions. According to both observation and theoretical arguments, NPF usually requires a relatively high sulfuric acid (H2SO4) concentration to promote the formation of new particles and a low preexisting aerosol loading to minimize the sink of new particles. We investigated NPF in Shanghai and were able to observe both precursor vapors (H2SO4) and initial clusters at a molecular level in a megacity. High NPF rates were observed to coincide with several familiar markers suggestive of H2SO4-dimethylamine (DMA)-water (H2O) nucleation, including sulfuric acid dimers and H2SO4-DMA clusters. In a cluster kinetics simulation, the observed concentration of sulfuric acid was high enough to explain the particle growth to ~3 nanometers under the very high condensation sink, whereas the subsequent higher growth rate beyond this size is believed to result from the added contribution of condensing organic species. These findings will help in understanding urban NPF and its air quality and climate effects, as well as in formulating policies to mitigate secondary particle formation in China.}, } @article {pmid30026224, year = {2018}, author = {Rosenblum, S and Reinhold, P and Mirrahimi, M and Jiang, L and Frunzio, L and Schoelkopf, RJ}, title = {Fault-tolerant detection of a quantum error.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {266-270}, doi = {10.1126/science.aat3996}, pmid = {30026224}, issn = {1095-9203}, abstract = {A critical component of any quantum error-correcting scheme is detection of errors by using an ancilla system. However, errors occurring in the ancilla can propagate onto the logical qubit, irreversibly corrupting the encoded information. We demonstrate a fault-tolerant error-detection scheme that suppresses spreading of ancilla errors by a factor of 5, while maintaining the assignment fidelity. The same method is used to prevent propagation of ancilla excitations, increasing the logical qubit dephasing time by an order of magnitude. Our approach is hardware-efficient, as it uses a single multilevel transmon ancilla and a cavity-encoded logical qubit, whose interaction is engineered in situ by using an off-resonant sideband drive. The results demonstrate that hardware-efficient approaches that exploit system-specific error models can yield advances toward fault-tolerant quantum computation.}, } @article {pmid30026223, year = {2018}, author = {Pham, T and Oh, S and Stetz, P and Onishi, S and Kisielowski, C and Cohen, ML and Zettl, A}, title = {Torsional instability in the single-chain limit of a transition metal trichalcogenide.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {263-266}, doi = {10.1126/science.aat4749}, pmid = {30026223}, issn = {1095-9203}, abstract = {The scientific bounty resulting from the successful isolation of few to single layers of two-dimensional materials suggests that related new physics resides in the few- to single-chain limit of one-dimensional materials. We report the synthesis of the quasi-one-dimensional transition metal trichalcogenide NbSe3 (niobium triselenide) in the few-chain limit, including the realization of isolated single chains. The chains are encapsulated in protective boron nitride or carbon nanotube sheaths to prevent oxidation and to facilitate characterization. Transmission electron microscopy reveals static and dynamic structural torsional waves not found in bulk NbSe3 crystals. Electronic structure calculations indicate that charge transfer drives the torsional wave instability. Very little covalent bonding is found between the chains and the nanotube sheath, leading to relatively unhindered longitudinal and torsional dynamics for the encapsulated chains.}, } @article {pmid30026222, year = {2018}, author = {Norcia, MA and Lewis-Swan, RJ and Cline, JRK and Zhu, B and Rey, AM and Thompson, JK}, title = {Cavity-mediated collective spin-exchange interactions in a strontium superradiant laser.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {259-262}, doi = {10.1126/science.aar3102}, pmid = {30026222}, issn = {1095-9203}, abstract = {Laser-cooled and quantum degenerate atoms are being pursued as quantum simulators and form the basis of today's most precise sensors. A key challenge toward these goals is to understand and control coherent interactions between the atoms. We observe long-range exchange interactions mediated by an optical cavity, which manifest as tunable spin-spin interactions on the pseudo spin-½ system composed of the millihertz linewidth clock transition in strontium. This leads to one-axis twisting dynamics, the emergence of a many-body energy gap, and gap protection of the optical coherence against certain sources of decoherence. Our observations will aid in the future design of versatile quantum simulators and the next generation of atomic clocks that use quantum correlations for enhanced metrology.}, } @article {pmid30026221, year = {2018}, author = {Doppagne, B and Chong, MC and Bulou, H and Boeglin, A and Scheurer, F and Schull, G}, title = {Electrofluorochromism at the single-molecule level.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {251-255}, doi = {10.1126/science.aat1603}, pmid = {30026221}, issn = {1095-9203}, abstract = {The interplay between the oxidation state and the optical properties of molecules is important for applications in displays, sensors, and molecular-based memories. The fundamental mechanisms occurring at the level of a single molecule have been difficult to probe. We used a scanning tunneling microscope (STM) to characterize and control the fluorescence of a single zinc-phthalocyanine radical cation adsorbed on a sodium chloride-covered gold (111) sample. The neutral and oxidized states of the molecule were identified on the basis of their fluorescence spectra, which revealed very different emission energies and vibronic fingerprints. The emission of the charged molecule was controlled by tuning the thickness of the insulator and the plasmons localized at the apex of the STM tip. In addition, subnanometric variations of the tip position were used to investigate the charging and electroluminescence mechanisms.}, } @article {pmid30026220, year = {2018}, author = {Wieder, BJ and Bradlyn, B and Wang, Z and Cano, J and Kim, Y and Kim, HD and Rappe, AM and Kane, CL and Bernevig, BA}, title = {Wallpaper fermions and the nonsymmorphic Dirac insulator.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {246-251}, doi = {10.1126/science.aan2802}, pmid = {30026220}, issn = {1095-9203}, abstract = {Materials whose gapless surface states are protected by crystal symmetries include mirror topological crystalline insulators and nonsymmorphic hourglass insulators. There exists only a very limited set of possible surface crystal symmetries, captured by the 17 "wallpaper groups." Here we show that a consideration of symmetry-allowed band degeneracies in the wallpaper groups can be used to understand previously described topological crystalline insulators and to predict phenomenologically distinct examples. In particular, the two wallpaper groups with multiple glide lines, pgg and p4g, allow for a topological insulating phase whose surface spectrum consists of only a single, fourfold-degenerate, true Dirac fermion, representing an exception to a symmetry-enhanced fermion-doubling theorem. We theoretically predict the presence of this phase in Sr2Pb3 in space group 127 (P4/mbm).}, } @article {pmid30026219, year = {2018}, author = {Rozell, DJ}, title = {A closer look at ageism in science.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {239}, doi = {10.1126/science.aau3997}, pmid = {30026219}, issn = {1095-9203}, mesh = {*Ageism ; }, } @article {pmid30026218, year = {2018}, author = {Sawarkar, R and Scherz-Shouval, R and Denzel, M and Saarikangas, J}, title = {Preparing junior faculty for success.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {238}, doi = {10.1126/science.aau4531}, pmid = {30026218}, issn = {1095-9203}, mesh = {*Faculty, Medical ; }, } @article {pmid30026217, year = {2018}, author = {Żmihorski, M and Chylarecki, P and Orczewska, A and Wesołowski, T}, title = {Białowieża Forest: A new threat.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {238}, doi = {10.1126/science.aau2708}, pmid = {30026217}, issn = {1095-9203}, mesh = {Animals ; Coleoptera ; *Environmental Restoration and Remediation ; *Forests ; Picea/*parasitology ; Poland ; }, } @article {pmid30026216, year = {2018}, author = {Nichols, L and Wynes, D}, title = {Engage research institutions on research regulatory reform.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {233-235}, doi = {10.1126/science.aat9482}, pmid = {30026216}, issn = {1095-9203}, } @article {pmid30026215, year = {2018}, author = {Tas, RP and Kapitein, LC}, title = {Exploring cytoskeletal diversity in neurons.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {231-232}, doi = {10.1126/science.aat5992}, pmid = {30026215}, issn = {1095-9203}, mesh = {Actin Cytoskeleton/*ultrastructure ; Animals ; Humans ; Microtubules/*ultrastructure ; Neurons/*cytology/*physiology ; Polymerization ; }, } @article {pmid30026214, year = {2018}, author = {Stewart, CN and Abudayyeh, RK and Stewart, SG}, title = {Houseplants as home health monitors.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {229-230}, doi = {10.1126/science.aau2560}, pmid = {30026214}, issn = {1095-9203}, mesh = {Arabidopsis/*genetics ; *Biosensing Techniques ; DNA Damage ; Environmental Monitoring/*methods ; Health ; Humans ; *Microbiota ; Mutation ; *Plants, Genetically Modified ; }, } @article {pmid30026213, year = {2018}, author = {Randel, WJ}, title = {The seasonal fingerprint of climate change.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {227-228}, doi = {10.1126/science.aat9097}, pmid = {30026213}, issn = {1095-9203}, mesh = {*Climate Change ; *Seasons ; }, } @article {pmid30026212, year = {2018}, author = {Sanchez, DJ and Simon, MC}, title = {Transcriptional control of kidney cancer.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {226-227}, doi = {10.1126/science.aau4385}, pmid = {30026212}, issn = {1095-9203}, mesh = {Gene Expression Regulation ; Humans ; Kidney ; *Kidney Neoplasms ; *Transcription, Genetic ; }, } @article {pmid30026211, year = {2018}, author = {Kortenkamp, A and Faust, M}, title = {Regulate to reduce chemical mixture risk.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {224-226}, doi = {10.1126/science.aat9219}, pmid = {30026211}, issn = {1095-9203}, mesh = {Animals ; Complex Mixtures/*toxicity ; Environmental Exposure/*legislation & jurisprudence/*standards ; Humans ; Risk ; Toxicology/*legislation & jurisprudence/*standards ; }, } @article {pmid30026210, year = {2018}, author = {Kümmerer, K and Dionysiou, DD and Olsson, O and Fatta-Kassinos, D}, title = {A path to clean water.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {222-224}, doi = {10.1126/science.aau2405}, pmid = {30026210}, issn = {1095-9203}, mesh = {Pharmaceutical Preparations/*isolation & purification/standards ; Waste Water/*chemistry ; Water Pollutants, Chemical/*isolation & purification/standards ; Water Purification/*methods/standards ; }, } @article {pmid30026209, year = {2018}, author = {Enserink, M}, title = {A second chance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {216-221}, doi = {10.1126/science.361.6399.216}, pmid = {30026209}, issn = {1095-9203}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Child ; *Disease Eradication ; Global Health ; Humans ; Neglected Diseases/*epidemiology/pathology/*prevention & control ; Papua New Guinea/epidemiology ; Physicians ; Skin Ulcer/microbiology/pathology ; Spain ; Treponema pallidum/pathogenicity ; Yaws/*epidemiology/pathology/*prevention & control/transmission ; }, } @article {pmid30026208, year = {2018}, author = {Hutson, M}, title = {Hackers easily fool artificial intelligences.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {215}, doi = {10.1126/science.361.6399.215}, pmid = {30026208}, issn = {1095-9203}, } @article {pmid30026207, year = {2018}, author = {Cohen, J}, title = {'Frightening' typhoid fever outbreak spreads in Pakistan.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {214}, doi = {10.1126/science.361.6399.214}, pmid = {30026207}, issn = {1095-9203}, mesh = {Administration, Intravenous ; Anti-Bacterial Agents/*administration & dosage/pharmacology ; *Disease Outbreaks ; Drinking Water/microbiology ; *Drug Resistance, Bacterial ; Humans ; Pakistan/epidemiology ; Prescription Drug Overuse ; Salmonella typhi/*drug effects/genetics/isolation & purification ; Sewage/microbiology ; Typhoid Fever/*drug therapy/*epidemiology ; }, } @article {pmid30026206, year = {2018}, author = {Vogel, G}, title = {Echidnas don't suck-but their ancestors did.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {213}, doi = {10.1126/science.361.6399.213}, pmid = {30026206}, issn = {1095-9203}, mesh = {*Adaptation, Physiological ; Animals ; Animals, Suckling/*anatomy & histology/*physiology ; Biological Evolution ; Echidna/*anatomy & histology/*physiology ; Fossils ; *Sucking Behavior ; }, } @article {pmid30026205, year = {2018}, author = {Kaiser, J}, title = {A new portal for patient data.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {212}, doi = {10.1126/science.361.6399.212}, pmid = {30026205}, issn = {1095-9203}, mesh = {*Clinical Trials as Topic ; *Data Anonymization ; Humans ; Information Dissemination/*methods ; }, } @article {pmid30026204, year = {2018}, author = {Cohen, J}, title = {Congo rapidly curtails Ebola.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {211-212}, doi = {10.1126/science.361.6399.211}, pmid = {30026204}, issn = {1095-9203}, mesh = {Democratic Republic of the Congo/epidemiology ; *Disease Eradication ; Disease Outbreaks/*prevention & control ; Ebola Vaccines/*administration & dosage ; Epidemiological Monitoring ; Hemorrhagic Fever, Ebola/*epidemiology/*prevention & control ; Humans ; Mass Vaccination/*statistics & numerical data ; }, } @article {pmid30026202, year = {2018}, author = {Baker, DN and Chandran, A}, title = {Space, still the final frontier.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {207}, doi = {10.1126/science.aau7631}, pmid = {30026202}, issn = {1095-9203}, } @article {pmid30026201, year = {2018}, author = {Santer, BD and Po-Chedley, S and Zelinka, MD and Cvijanovic, I and Bonfils, C and Durack, PJ and Fu, Q and Kiehl, J and Mears, C and Painter, J and Pallotta, G and Solomon, S and Wentz, FJ and Zou, CZ}, title = {Human influence on the seasonal cycle of tropospheric temperature.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {}, doi = {10.1126/science.aas8806}, pmid = {30026201}, issn = {1095-9203}, mesh = {*Climate Change ; *Human Activities ; Humans ; Satellite Imagery ; *Seasons ; *Temperature ; }, abstract = {We provide scientific evidence that a human-caused signal in the seasonal cycle of tropospheric temperature has emerged from the background noise of natural variability. Satellite data and the anthropogenic "fingerprint" predicted by climate models show common large-scale changes in geographical patterns of seasonal cycle amplitude. These common features include increases in amplitude at mid-latitudes in both hemispheres, amplitude decreases at high latitudes in the Southern Hemisphere, and small changes in the tropics. Simple physical mechanisms explain these features. The model fingerprint of seasonal cycle changes is identifiable with high statistical confidence in five out of six satellite temperature datasets. Our results suggest that attribution studies with the changing seasonal cycle provide powerful evidence for a significant human effect on Earth's climate.}, } @article {pmid30026200, year = {2018}, author = {Rangel, TF and Edwards, NR and Holden, PB and Diniz-Filho, JAF and Gosling, WD and Coelho, MTP and Cassemiro, FAS and Rahbek, C and Colwell, RK}, title = {Modeling the ecology and evolution of biodiversity: Biogeographical cradles, museums, and graves.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {}, doi = {10.1126/science.aar5452}, pmid = {30026200}, issn = {1095-9203}, mesh = {*Biodiversity ; *Climate Change ; *Computer Simulation ; *Models, Theoretical ; Phylogeography ; Population Dynamics ; South America ; Spatio-Temporal Analysis ; }, abstract = {Individual processes shaping geographical patterns of biodiversity are increasingly understood, but their complex interactions on broad spatial and temporal scales remain beyond the reach of analytical models and traditional experiments. To meet this challenge, we built a spatially explicit, mechanistic simulation model implementing adaptation, range shifts, fragmentation, speciation, dispersal, competition, and extinction, driven by modeled climates of the past 800,000 years in South America. Experimental topographic smoothing confirmed the impact of climate heterogeneity on diversification. The simulations identified regions and episodes of speciation (cradles), persistence (museums), and extinction (graves). Although the simulations had no target pattern and were not parameterized with empirical data, emerging richness maps closely resembled contemporary maps for major taxa, confirming powerful roles for evolution and diversification driven by topography and climate.}, } @article {pmid30026199, year = {2018}, author = {Godfray, HCJ and Aveyard, P and Garnett, T and Hall, JW and Key, TJ and Lorimer, J and Pierrehumbert, RT and Scarborough, P and Springmann, M and Jebb, SA}, title = {Meat consumption, health, and the environment.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {}, doi = {10.1126/science.aam5324}, pmid = {30026199}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Diet ; *Environment ; Food Supply/*economics ; *Health ; Humans ; Livestock ; Meat/*adverse effects/*economics ; Population Growth ; }, abstract = {Both the global average per capita consumption of meat and the total amount of meat consumed are rising, driven by increasing average individual incomes and by population growth. The consumption of different types of meat and meat products has substantial effects on people's health, and livestock production can have major negative effects on the environment. Here, we explore the evidence base for these assertions and the options policy-makers have should they wish to intervene to affect population meat consumption. We highlight where more research is required and the great importance of integrating insights from the natural and social sciences.}, } @article {pmid30026198, year = {2018}, author = {Garrido-Charad, F and Vega-Zuniga, T and Gutiérrez-Ibáñez, C and Fernandez, P and López-Jury, L and González-Cabrera, C and Karten, HJ and Luksch, H and Marín, GJ}, title = {"Shepherd's crook" neurons drive and synchronize the enhancing and suppressive mechanisms of the midbrain stimulus selection network.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7615-E7623}, pmid = {30026198}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; Chickens/*physiology ; Neuroanatomical Tract-Tracing Techniques/methods ; Neurons/*physiology ; Photic Stimulation ; Superior Colliculi/cytology/*physiology ; Visual Pathways/*physiology ; }, abstract = {The optic tectum (TeO), or superior colliculus, is a multisensory midbrain center that organizes spatially orienting responses to relevant stimuli. To define the stimulus with the highest priority at each moment, a network of reciprocal connections between the TeO and the isthmi promotes competition between concurrent tectal inputs. In the avian midbrain, the neurons mediating enhancement and suppression of tectal inputs are located in separate isthmic nuclei, facilitating the analysis of the neural processes that mediate competition. A specific subset of radial neurons in the intermediate tectal layers relay retinal inputs to the isthmi, but at present it is unclear whether separate neurons innervate individual nuclei or a single neural type sends a common input to several of them. In this study, we used in vitro neural tracing and cell-filling experiments in chickens to show that single neurons innervate, via axon collaterals, the three nuclei that comprise the isthmotectal network. This demonstrates that the input signals representing the strength of the incoming stimuli are simultaneously relayed to the mechanisms promoting both enhancement and suppression of the input signals. By performing in vivo recordings in anesthetized chicks, we also show that this common input generates synchrony between both antagonistic mechanisms, demonstrating that activity enhancement and suppression are closely coordinated. From a computational point of view, these results suggest that these tectal neurons constitute integrative nodes that combine inputs from different sources to drive in parallel several concurrent neural processes, each performing complementary functions within the network through different firing patterns and connectivity.}, } @article {pmid30026197, year = {2018}, author = {Seo, D and Schrader, AM and Chen, SY and Kaufman, Y and Cristiani, TR and Page, SH and Koenig, PH and Gizaw, Y and Lee, DW and Israelachvili, JN}, title = {Rates of cavity filling by liquids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8070-8075}, pmid = {30026197}, issn = {1091-6490}, support = {S10 OD010610/OD/NIH HHS/United States ; }, mesh = {Air ; Fluorescein/chemistry ; *Hydrophobic and Hydrophilic Interactions ; Meniscus/chemistry ; Phase Transition ; Pressure ; Silicon/chemistry ; Solubility ; Surface Properties ; Surface-Active Agents/chemistry ; *Thermodynamics ; Volatilization ; Water/chemistry ; *Wettability ; }, abstract = {Understanding the fundamental wetting behavior of liquids on surfaces with pores or cavities provides insights into the wetting phenomena associated with rough or patterned surfaces, such as skin and fabrics, as well as the development of everyday products such as ointments and paints, and industrial applications such as enhanced oil recovery and pitting during chemical mechanical polishing. We have studied, both experimentally and theoretically, the dynamics of the transitions from the unfilled/partially filled (Cassie-Baxter) wetting state to the fully filled (Wenzel) wetting state on intrinsically hydrophilic surfaces (intrinsic water contact angle <90°, where the Wenzel state is always the thermodynamically favorable state, while a temporary metastable Cassie-Baxter state can also exist) to determine the variables that control the rates of such transitions. We prepared silicon wafers with cylindrical cavities of different geometries and immersed them in bulk water. With bright-field and confocal fluorescence microscopy, we observed the details of, and the rates associated with, water penetration into the cavities from the bulk. We find that unconnected, reentrant cavities (i.e., cavities that open up below the surface) have the slowest cavity-filling rates, while connected or non-reentrant cavities undergo very rapid transitions. Using these unconnected, reentrant cavities, we identified the variables that affect cavity-filling rates: (i) the intrinsic contact angle, (ii) the concentration of dissolved air in the bulk water phase (i.e., aeration), (iii) the liquid volatility that determines the rate of capillary condensation inside the cavities, and (iv) the presence of surfactants.}, } @article {pmid30026196, year = {2018}, author = {Vermaas, JV and Rempe, SB and Tajkhorshid, E}, title = {Electrostatic lock in the transport cycle of the multidrug resistance transporter EmrE.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7502-E7511}, pmid = {30026196}, issn = {1091-6490}, support = {P41 GM104601/GM/NIGMS NIH HHS/United States ; U54 GM087519/GM/NIGMS NIH HHS/United States ; }, mesh = {Antiporters/chemistry/*metabolism ; Biological Transport ; Cryoelectron Microscopy ; *Drug Resistance, Multiple, Bacterial ; Escherichia coli/*physiology ; Escherichia coli Proteins/chemistry/*metabolism ; Glutamic Acid/chemistry/*metabolism ; Hydrogen Bonding ; Lipid Bilayers/chemistry ; Molecular Dynamics Simulation ; Protein Binding ; Protein Conformation ; Protons ; Static Electricity ; }, abstract = {EmrE is a small, homodimeric membrane transporter that exploits the established electrochemical proton gradient across the Escherichia coli inner membrane to export toxic polyaromatic cations, prototypical of the wider small-multidrug resistance transporter family. While prior studies have established many fundamental aspects of the specificity and rate of substrate transport in EmrE, low resolution of available structures has hampered identification of the transport coupling mechanism. Here we present a complete, refined atomic structure of EmrE optimized against available cryo-electron microscopy (cryo-EM) data to delineate the critical interactions by which EmrE regulates its conformation during the transport process. With the model, we conduct molecular dynamics simulations of the transporter in explicit membranes to probe EmrE dynamics under different substrate loading and conformational states, representing different intermediates in the transport cycle. The refined model is stable under extended simulation. The water dynamics in simulation indicate that the hydrogen-bonding networks around a pair of solvent-exposed glutamate residues (E14) depend on the loading state of EmrE. One specific hydrogen bond from a tyrosine (Y60) on one monomer to a glutamate (E14) on the opposite monomer is especially critical, as it locks the protein conformation when the glutamate is deprotonated. The hydrogen bond provided by Y60 lowers the [Formula: see text] of one glutamate relative to the other, suggesting both glutamates should be protonated for the hydrogen bond to break and a substrate-free transition to take place. These findings establish the molecular mechanism for the coupling between proton transfer reactions and protein conformation in this proton-coupled secondary transporter.}, } @article {pmid30026195, year = {2018}, author = {Cheke, RA}, title = {New pests for old as GMOs bring on substitute pests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8239-8240}, pmid = {30026195}, issn = {1091-6490}, mesh = {*Food, Genetically Modified ; *Plants, Genetically Modified ; }, } @article {pmid30026194, year = {2018}, author = {Small, ML}, title = {Understanding when people will report crimes to the police.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8057-8059}, pmid = {30026194}, issn = {1091-6490}, mesh = {*Crime ; *Police ; }, } @article {pmid30026124, year = {2018}, author = {Ferreira, M and Fernandes, AM and Aleixo, A and Antonelli, A and Olsson, U and Bates, JM and Cracraft, J and Ribas, CC}, title = {Evidence for mtDNA capture in the jacamar Galbula leucogastra/chalcothorax species-complex and insights on the evolution of white-sand ecosystems in the Amazon basin.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {149-157}, doi = {10.1016/j.ympev.2018.07.007}, pmid = {30026124}, issn = {1095-9513}, abstract = {Jacamar species occur throughout Amazonia, with most species occupying forested habitats. One species-complex, Galbula leucogastra/chalcothorax, is associated to white sand ecosystems (WSE). Previous studies of WSE bird species recovered shallow genetic structure in mtDNA coupled with signs of gene flow among WSE patches. Here, we characterize diversification of the G. leucogastra/chalcothorax species-complex with dense sampling across its distribution using mitochondrial and genomic (Ultraconserved Elements, UCEs) DNA sequences. We performed concatenated likelihood and Bayesian analysis, as well as a species-tree analysis using ∗BEAST, to establish the phylogenetic relationships among populations. The mtDNA results recovered at least six geographically-structured lineages, with G. chalcothorax embedded within lineages of G. leucogastra. In contrast, both concatenated and species-tree analyses of UCE data recovered G. chalcothorax as sister to all G. leucogastra lineages. We hypothesize that the mitochondrial genome of one of the G. leucogastra lineage (Madeira) was captured into G. chalcothorax in the past. We discuss how WSE evolution and the coevolution of mtDNA and nuclear genes might have played a role in this apparently rare event.}, } @article {pmid30026123, year = {2018}, author = {Niu, YT and Jabbour, F and Barrett, RL and Ye, JF and Zhang, ZZ and Lu, KQ and Lu, LM and Chen, ZD}, title = {Combining complete chloroplast genome sequences with target loci data and morphology to resolve species limits in Triplostegia (Caprifoliaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {15-26}, doi = {10.1016/j.ympev.2018.07.013}, pmid = {30026123}, issn = {1095-9513}, abstract = {Species represent the most basic unit of taxonomy. As such, species delimitation represents a crucial issue for biodiversity conservation. Taxonomic practices were revolutionized in the last three decades due to the increasing availability of molecular phylogenetic data. The genus Triplostegia (Caprifoliaceae) traditionally consists of two species, T. glandulifera and T. grandiflora, distinguishable mainly based on quantitative morphological features. In this study, we sequenced nine chloroplast loci (i.e., accD, psbK-psbI, rbcL-accD, rpoB-trnC, rps16-trnQ, trnE-trnT, trnF-ndhJ, trnH-psbA, trnS-trnG) and one nuclear locus (ITS) of 16 individuals of Triplostegia representing the entire distribution range of both species recognized. Furthermore, we also obtained whole chloroplast sequences for 11 of the 16 individuals for which silica gel-dried leaves were available. Our phylogenetic analyses integrating chloroplast genome sequences and multiple loci data revealed that Triplostegia includes four main clades that largely match geography. Neither T. grandiflora nor T. glandulifera was recovered as monophyletic and no diagnosable differences in leaf, flower, and pollen traits were detected between the two species, indicating the need for a revised species circumscription within Triplostegia. Our study highlights the importance of combining data from different sources while defining species limits.}, } @article {pmid30026122, year = {2018}, author = {Goyal, Y and Schüpbach, T and Shvartsman, SY}, title = {A quantitative model of developmental RTK signaling.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {80-86}, doi = {10.1016/j.ydbio.2018.07.012}, pmid = {30026122}, issn = {1095-564X}, mesh = {Animals ; Body Patterning/genetics/*physiology ; Drosophila/genetics/metabolism ; Drosophila Proteins/genetics/metabolism ; Gene Expression Regulation, Developmental/genetics ; Protein-Tyrosine Kinases/metabolism ; Proto-Oncogene Proteins p21(ras)/metabolism ; Receptor Protein-Tyrosine Kinases/*metabolism/*physiology ; Signal Transduction/genetics ; }, abstract = {Receptor tyrosine kinases (RTKs) control a wide range of developmental processes, from the first stages of embryogenesis to postnatal growth and neurocognitive development in the adult. A significant share of our knowledge about RTKs comes from genetic screens in model organisms, which provided numerous examples demonstrating how specific cell fates and morphologies are abolished when RTK activation is either abrogated or significantly reduced. Aberrant activation of such pathways has also been recognized in many forms of cancer. More recently, studies of human developmental syndromes established that excessive activation of RTKs and their downstream signaling effectors, most notably the Ras signaling pathway, can also lead to structural and functional defects. Given that both insufficient and excessive pathway activation can lead to abnormalities, mechanistic analysis of developmental RTK signaling must address quantitative questions about its regulation and function. Patterning events controlled by the RTK Torso in the early Drosophila embryo are well-suited for this purpose. This mini review summarizes current state of knowledge about Torso-dependent Ras activation and discusses its potential to serve as a quantitative model for studying the general principles of Ras signaling in development and disease.}, } @article {pmid30026121, year = {2018}, author = {Molotkov, A and Soriano, P}, title = {Distinct mechanisms for PDGF and FGF signaling in primitive endoderm development.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {155-161}, pmid = {30026121}, issn = {1095-564X}, support = {P30 CA196521/CA/NCI NIH HHS/United States ; R01 DE022778/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Blastocyst/metabolism ; Blastocyst Inner Cell Mass/metabolism ; Cell Differentiation/physiology ; Cell Lineage/physiology ; Embryo, Mammalian/metabolism ; Embryonic Development ; Endoderm/metabolism ; Fibroblast Growth Factor 4/*metabolism/physiology ; Fibroblast Growth Factors/metabolism ; Germ Layers/metabolism ; MAP Kinase Signaling System/physiology ; Mice ; Mice, Transgenic ; Phosphatidylinositol 3-Kinases/metabolism ; Platelet-Derived Growth Factor/*metabolism/physiology ; Receptor, Fibroblast Growth Factor, Type 1/metabolism ; Receptor, Fibroblast Growth Factor, Type 2/metabolism ; Receptor, Fibroblast Growth Factor, Type 4/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Signal Transduction/physiology ; }, abstract = {FGF signaling is known to play a critical role in the specification of primitive endoderm (PrE) and epiblast (Epi) from the inner cell mass (ICM) during mouse preimplantation development, but how FGFs synergize with other growth factor signaling pathways is unknown. Because PDGFRα signaling has also been implicated in the PrE, we investigated the coordinate functions of PDGFRα together with FGFR1 or FGFR2 in PrE development. PrE development was abrogated in Pdgfra; Fgfr1 compound mutants, or significantly reduced in Pdgfra; Fgfr2 or PdgfraPI3K; Fgfr2 compound mutants. We provide evidence that both Fgfr2 and Pdgfra play roles in PrE cell survival while Fgfr1 controls PrE cell specification. Our results suggest a model where FGFR1-engaged ERK1/2 signaling governs PrE specification while PDGFRα- and by analogy possibly FGFR2- engaged PI3K signaling regulates PrE survival and positioning in the embryo. Together, these studies indicate how multiple growth factors and signaling pathways can cooperate in preimplantation development.}, } @article {pmid30026120, year = {2018}, author = {Iwase, A and Mita, K and Favero, DS and Mitsuda, N and Sasaki, R and Kobayshi, M and Takebayashi, Y and Kojima, M and Kusano, M and Oikawa, A and Sakakibara, H and Saito, K and Imamura, J and Sugimoto, K}, title = {WIND1 induces dynamic metabolomic reprogramming during regeneration in Brassica napus.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {40-52}, doi = {10.1016/j.ydbio.2018.07.006}, pmid = {30026120}, issn = {1095-564X}, mesh = {Arabidopsis/genetics ; Arabidopsis Proteins/*genetics/metabolism/*physiology ; Brassica napus/*genetics ; Cellular Reprogramming/genetics/physiology ; Cytokinins/metabolism ; Gene Expression Regulation, Plant/drug effects/genetics ; Genes, Plant ; Indoleacetic Acids/metabolism ; Organogenesis, Plant/genetics ; Plant Shoots/metabolism ; Plants, Genetically Modified ; Proline ; Putrescine ; Regeneration/genetics ; Transcription Factors/*genetics/metabolism/*physiology ; gamma-Aminobutyric Acid ; }, abstract = {Plants often display a high competence for regeneration under stress conditions. Signals produced in response to various types of stress serve as critical triggers for de novo organogenesis, but the identity of these signaling molecules underlying cellular reprogramming are largely unknown. We previously identified an AP2/ERF transcription factor, WOUND INDUCED DEDIFFERENTIATION1 (WIND1), as a key regulator involved in wound-induced cellular reprogramming in Arabidopsis. In this study, we found that activation of Arabidopsis WIND1 (AtWIND1) in hypocotyl explants of Brassica napus (B. napus) enhances callus formation and subsequent organ regeneration. Gene expression analyses revealed that AtWIND1 enhances expression of B. napus homologs of ENHANCER OF SHOOT REGENERATION1/DORNRÖSCHEN (ESR1/DRN), which is a direct target of WIND1 in Arabidopsis. Further, time-course hormonal analyses showed that an altered balance of endogenous auxin/cytokinin exists in AtWIND1-activated B. napus explants. Our mass spectrometry analyses, in addition, uncovered dynamic metabolomic reprogramming in AtWIND1-activated explants, including accumulation of several compounds, e.g. proline, gamma aminobutyric acid (GABA), and putrescine, that have historically been utilized as additives to enhance plant cell reprogramming in tissue culture. Our findings thus provide new insights into how WIND1 functions to promote cell reprogramming.}, } @article {pmid30025977, year = {2018}, author = {Yi, H and Kim, HS}, title = {Antibiotic Scars Left on the Gut Microbiota from the Stringent Response.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {735-737}, doi = {10.1016/j.tim.2018.06.003}, pmid = {30025977}, issn = {1878-4380}, abstract = {Current research is primarily focused on compositional shifts and alterations in the metabolic status of the gut microbiota to elucidate the damage caused by antibiotics. However, the impact of the stringent response, which is governed by a global gene regulatory system conserved in most gut bacteria, should not be overlooked.}, } @article {pmid30025872, year = {2018}, author = {Cowgill, LW and Johnston, RA}, title = {Biomechanical implications of the onset of walking.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {133-145}, doi = {10.1016/j.jhevol.2018.06.003}, pmid = {30025872}, issn = {1095-8606}, abstract = {Changes in long bone strength associated with the onset of bipedal walking in humans have been previously documented in a longitudinal growth sample. However, it is unclear if this transition can be detected using archaeological, cross-sectional data, which likely encompass more cultural and biological variation than a single dataset of living children. Focusing on variation in cross-sectional polar second moment of area, we evaluate the ratios of femoral, tibial, and humeral strength in seven temporally diverse samples of individuals from birth to the age of eighteen years (n = 501), with subsequent comparisons to immature Late Pleistocene fossils. Using these samples, we determine whether changes related to the developmental onset of bipedality can be detected in a large, multi-population sample, test for differences in long bone strength ratios among Holocene groups that may indicate developmental differences in the onset of walking, and determine whether immature Late Pleistocene samples follow the same patterns as modern humans. Despite great variation within the Holocene sample, clear changes in these ratios are apparent around the age of the onset of walking. Humeral-to-femoral strength increases briefly prior to the age of one, with a sharp decline in relative humeral strength thereafter until age four. A similar pattern is apparent in the ratio of humeral/tibial and femoral/tibial strength. While the general pattern is consistent across all human groups sampled, these ratios vary by skeletal population, which seems to be closely related to variation in tibial length among samples. Although the extremely small fossil sample makes differences difficult to interpret, Neandertals also differ from both Late Pleistocene and Holocene modern humans in their strength ratios. Further research in this area may provide additional information about the skeletal impact of the onset of walking in the past and in additional fossil taxa.}, } @article {pmid30025871, year = {2018}, author = {Belcastro, MG and Mariotti, V and Riga, A and Bonfiglioli, B and Frayer, DW}, title = {Tooth fractures in the Krapina Neandertals.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {96-108}, doi = {10.1016/j.jhevol.2018.06.009}, pmid = {30025871}, issn = {1095-8606}, abstract = {Dental fractures can be produced during life or post-mortem. Ante-mortem chipping may be indicative of different uses of the dentition in masticatory and non-masticatory activities related to variable diets and behaviors. The Krapina collection (Croatia, 130,000 years BP), thanks to the large number of teeth (293 teeth and tooth fragments) within it, offers an excellent sample to investigate dental fractures systematically. Recorded were the distribution, position and severity of the ante-mortem fractures according to standardized methods. High frequencies of teeth with chipping in both Krapina adults and subadults suggest that the permanent and deciduous dentition were heavily subjected to mechanical stress. This is particularly evident when the frequencies of chipping are compared with those in modern humans (Upper Paleolithic and historic samples) that we analysed using the same methods. The distribution of chipping in the Krapina sample (anterior teeth are more affected) and its position (labial) suggest a systematic use of the anterior teeth for non-masticatory tasks.}, } @article {pmid30025666, year = {2018}, author = {Cvijović, I and Nguyen Ba, AN and Desai, MM}, title = {Experimental Studies of Evolutionary Dynamics in Microbes.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {9}, pages = {693-703}, doi = {10.1016/j.tig.2018.06.004}, pmid = {30025666}, issn = {0168-9525}, abstract = {Evolutionary dynamics in laboratory microbial evolution experiments can be surprisingly complex. In the past two decades, observations of these dynamics have challenged simple models of adaptation and have shown that clonal interference, hitchhiking, ecological diversification, and contingency are widespread. In recent years, advances in high-throughput strain maintenance and phenotypic assays, the dramatically reduced cost of genome sequencing, and emerging methods for lineage barcoding have made it possible to observe evolutionary dynamics at unprecedented resolution. These new methods can now begin to provide detailed measurements of key aspects of fitness landscapes and of evolutionary outcomes across a range of systems. These measurements can highlight challenges to existing theoretical models and guide new theoretical work towards the complications that are most widely important.}, } @article {pmid30025466, year = {2018}, author = {Leding, JK and Toglia, MP}, title = {Adaptive Memory: Survival Processing and Social Isolation.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {3}, pages = {1474704918789297}, doi = {10.1177/1474704918789297}, pmid = {30025466}, issn = {1474-7049}, mesh = {Adaptation, Psychological/*physiology ; Analysis of Variance ; Discrimination (Psychology) ; Female ; Humans ; Male ; Memory/physiology ; Mental Processes/*physiology ; Social Isolation/*psychology ; Survival/*psychology ; }, abstract = {Social isolation was examined to assess its potential influence on the survival processing effect, which shows that individuals are more likely to remember something when it is processed with regard to their survival. Participants imagined being stranded in the grasslands, going on a space mission, or moving to a foreign land while alone or with a group of friends and rated a list of words for their relevance to the assigned scenario. An incidental memory test showed the typical survival processing effect on recall memory, with a significant interaction showing that the effect occurred in the isolated condition but not in the group condition. A second experiment examined rates of recognition for an isolated and group condition for the grasslands and moving scenarios and found a marginally significant effect of isolation in addition to the typical survival processing effect. Further, in both experiments, the perceived isolation of the isolated and group survival grasslands scenarios was significantly higher than the other conditions. The results are discussed with regard to the self-reference effect and the object-function account of the survival processing effect.}, } @article {pmid30024374, year = {2018}, author = {Chen, H and Han, L and Feng, Q and Fan, Q and Lv, J}, title = {Hymenobacter bucti sp. nov., isolated from subsurface sandstone sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2749-2754}, doi = {10.1099/ijsem.0.002866}, pmid = {30024374}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-reaction-negative, strictly aerobic, non-motile, non-spore-forming bacterial strain, designated DK6-66T, was isolated from subsurface sandstone sediment located in the Qilian Mountains in Qinghai Province, Northwest China. Strain DK6-66T was found to grow optimally at pH 7.0 and 22 °C. The 16S rRNA gene sequence analysis indicated that strain DK6-66T belonged to the genus Hymenobacter and clustered with the type strain of Hymenobacter arcticus, with which it exhibited a 16S rRNA gene sequence similarity value of 98.2 %. The DNA G+C content was 60.4 mol%. The major respiratory quinone was MK-7 and the major polar lipid was phosphatidylethanolamine. The major fatty acids were C16 : 1ω7c and/or C16 : 1ω6c, anteiso-C17 : 1 B and/or iso-C17 : 1 I, iso-C15 : 0, anteiso-C15 : 0 and C16 : 1ω5c. On the basis of phylogenetic and phenotypic data, strain DK6-66T was classified in the genus Hymenobacter as a member of a novel species, for which the name Hymenobacterbucti sp. nov. is proposed. The type strain is DK6-66T (=CGMCC 1.15795T=KCTC 52629T).}, } @article {pmid30024371, year = {2018}, author = {Green, PN and Ardley, JK}, title = {Review of the genus Methylobacterium and closely related organisms: a proposal that some Methylobacterium species be reclassified into a new genus, Methylorubrum gen. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2727-2748}, doi = {10.1099/ijsem.0.002856}, pmid = {30024371}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Methylobacterium/*classification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The genus Methylobacterium, when first proposed by Patt et al. in 1976, was a monospecific genus created to accommodate a single pink pigmented facultatively methylotrophic bacterium. The genus now has over 50 validly published species, however, the percentage 16S rRNA sequence divergence within Methylobacterium questions whether or not they can still be accommodated within one genus. Additionally, several strains are described as belonging to Methylobacterium, but nodulate legumes and in some cases are unable to utilize methanol as a sole carbon source. This study reviews and discusses the current taxonomic status of Methylobacterium. Based on 16S rRNA gene, multi-locus sequence analysis, genomic and phenotypic data, the 52 Methylobacterium species can no longer be retained in one genus. Consequently, a new genus, Methylorubrum gen. nov., is proposed to accommodate 11 species previously held in Methylobacterium. The reclassified species names are proposed as: Methylorubrum aminovorans comb. nov. (type strain TH-15T=NCIMB 13343T=DSM 8832T), Methylorubrum extorquens comb. nov. (type strain NCIMB 9399T=DSM 1337T), Methylorubrum podarium comb. nov. (type strain FM4T=NCIMB 14856T=DSM 15083T), Methylorubrum populi comb. nov. (type strain BJ001T=NCIMB 13946T=ATCC BAA-705T), Methylorubrum pseudosasae comb. nov. (type strain BL44T=ICMP 17622T=NBRC 105205T), Methylorubrum rhodesianum comb. nov. (type strain NCIMB 12249T=DSM 5687T), Methylorubrum rhodinum comb. nov. (type strain NCIMB 9421T=DSM 2163T), Methylorubrum salsuginis comb. nov. (type strain MRT=NCIMB 14847T=NCCB 100140T), Methylorubrum suomiense comb. nov. (type strain F20T=NCIMB 13778T=DSM 14458T), Methylorubrum thiocyanatum comb. nov. (type strain ALL/SCN-PT=NCIMB 13651T=DSM 11490T) and Methylorubrum zatmanii comb. nov. (type strain NCIMB 12243T=DSM 5688T). The taxonomic position of several remaining species is also discussed.}, } @article {pmid30024362, year = {2018}, author = {Chen, P and Li, S and Li, QX}, title = {Pseudomonas tianjinensis sp. nov., isolated from domestic sewage.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2760-2769}, doi = {10.1099/ijsem.0.002799}, pmid = {30024362}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pseudomonas/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-negative bacterium, designated as type strain 68T, was isolated from domestic sewage in Tianjin, China. Cells of strain 68T were aerobic, motile and rod-shaped. The organism grew at 15-42 °C, pH 6.0-11.0 and with 0-4 % NaCl (w/v). The DNA G+C content was 61.9 mol%. The major fatty acids (>10 %) were summed feature 8 (C18 : 1ω7c), summed feature 3 (C16 : 1ω7c or C16 : 1ω6c), C16 : 0 and C12 : 0. The respiratory quinone was Q9. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and an unidentified aminophospholipid. Phylogenetic analysis based on full 16S rRNA gene sequences showed that strain 68T was a member of the genus Pseudomonas and showed similarities to Pseudomonas toyotomiensis HT-3T (98.58 %), Pseudomonas chengduensis MBRT (98.53 %), Pseudomonas alcaliphila AL15-21T (98.44 %), Pseudomonas composti C2T (97.75 %) and Pseudomonas anguilliseptica NCIMB 1949T (97.66 %). Strain 68T exhibited low DNA-DNA hybridization homology with P. alcaliphila AL15-21T (35.40 %), P. toyotomiensis HT-3T (33.30 %), P. chengduensis MBRT (35.40 %), P. anguilliseptica NCIMB 1949T (14.40 %) and P. composti C2T (20.40 %). On the basis of phenotypic, genotypic and phylogenetic evidence, strain 68T is considered to represent a novel species of the genus Pseudomonas, for which the name Pseudomonas tainjinensis sp. nov. is proposed. The type strain is 68T (=CICC 24204T=KCTC 52977T).}, } @article {pmid30024361, year = {2018}, author = {Fedi, S and Cappelletti, M and Sandri, F and Turner, RJ and Zannoni, D}, title = {Some facts about the respiratory enzymes of Pseudomonas pseudoalcaligenes KF707 recently renamed as Pseudomonas furukawaii sp. nov., type strain KF707.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {3066-3067}, doi = {10.1099/ijsem.0.002923}, pmid = {30024361}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Oxidation-Reduction ; *Phylogeny ; Pseudomonas pseudoalcaligenes/classification/*enzymology ; }, abstract = {Kimura and co-workers (Kimura N et al. Int J Syst Evol Microbiol 2018;68:1429-1435) recently proposed renaming the obligate aerobe Pseudomonas pseudoalcaligenes KF707 as Pseudomonas furukawiisp. nov. type strain KF707. Since the first quasi-complete genome sequence of KF707 was reported in 2012 (accession number: PRJNA83639) numerous reports on chemotaxis and function/composition of the respiratory redox chain of KF707 have been published, demonstrating that KF707 contains three cheA genes for aerobic motility, four cytochrome oxidases of c(c)aa3- and cbb3-type and one bd-type quinol oxidase. With this background in mind, it has been quite a surprise to read within Table 1 of the paper by Kimura et al. that strain KF707 is phenotypically characterized as cytochrome oxidase-negative. Further, Table 1 also reports that KF707 is β-galactosidase-positive, an affirmation that is not consistent with results documented in the current literature. In this present 'Letter to the Editor' we show that Kimura et al. have contradicted themselves and provided inaccurate information in respect to the respiratory phenotypic features of P. furukawii. Based on this, an official corrigendum is requested since the publication, as it is, blurs the credibility of the International Journal of Systematic and Evolutionary Microbiology.}, } @article {pmid30024089, year = {2018}, author = {Wang, Y and Ni, T and Wang, W and Liu, F}, title = {Gene transcription in bursting: a unified mode for realizing accuracy and stochasticity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12452}, pmid = {30024089}, issn = {1469-185X}, abstract = {There is accumulating evidence that, from bacteria to mammalian cells, messenger RNAs (mRNAs) are produced in intermittent bursts - a much 'noisier' process than traditionally thought. Based on quantitative measurements at individual promoters, diverse phenomenological models have been proposed for transcriptional bursting. Nevertheless, the underlying molecular mechanisms and significance for cellular signalling remain elusive. Here, we review recent progress, address the above issues and illuminate our viewpoints with simulation results. Despite being widely used in modelling and in interpreting experimental data, the traditional two-state model is far from adequate to describe or infer the molecular basis and stochastic principles of transcription. In bacteria, DNA supercoiling contributes to the bursting of those genes that express at high levels and are topologically constrained in short loops; moreover, low-affinity cis-regulatory elements and unstable protein complexes can play a key role in transcriptional regulation. Integrating data on the architecture, kinetics, and transcriptional input-output function is a promising approach to uncovering the underlying dynamic mechanism. For eukaryotes, distinct bursting features described by the multi-scale and continuum models coincide with those predicted by four theoretically derived principles that govern how the transcription apparatus operates dynamically. This consistency suggests a unified framework for comprehending bursting dynamics at the level of the structural and kinetic basis of transcription. Moreover, the existing models can be unified by a generic model. Remarkably, transcriptional bursting enables regulatory information to be transmitted in a digital manner, with the burst frequency representing the strength of regulatory signals. Such a mode guarantees high fidelity for precise transcriptional regulation and also provides sufficient randomness for realizing cellular heterogeneity.}, } @article {pmid30024026, year = {2018}, author = {Ali, N}, title = {Digest: Stress and inbreeding depression in Drosophila melanogaster.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13524}, pmid = {30024026}, issn = {1558-5646}, abstract = {Do stressful conditions exacerbate inbreeding depression? Using Drosophila melanogaster, Schou et al. (2018) examine the mechanisms underlying the interaction between stress and inbreeding depression. The authors found that gene expression in inbred individuals was highly stochastic under benign conditions, but differential gene expression in inbred individuals was reduced compared to controls under stressful conditions.}, } @article {pmid30022808, year = {2018}, author = {Lang, SA and Shain, DH}, title = {Atypical Evolution of the F1Fo Adenosine Triphosphate Synthase Regulatory ATP6 subunit in Glacier Ice Worms (Annelida: Clitellata: Mesenchytraeus).}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318788076}, pmid = {30022808}, issn = {1176-9343}, abstract = {The glacier ice worm, Mesenchytraeus solifugus, is among a few animals that reside permanently in glacier ice. Their adaptation to cold temperature has been linked to relatively high intracellular adenosine triphosphate (ATP) levels, which compensate for reductions in molecular motion at low physiological temperatures. Here, we show that ATP6-the critical regulatory subunit of the F1Fo-ATP synthase and primary target of mitochondrial disease-acquired an unprecedented histidine-rich, 18-amino acid carboxy-terminal extension, which counters the strong evolutionary trend of mitochondrial genome compaction. Furthermore, sequence analysis suggests that this insertion is not of metazoan origin, but rather is a product of horizontal gene transfer from a microbial dietary source, and may act as a proton shuttle to accelerate the rate of ATP synthesis.}, } @article {pmid30022612, year = {2018}, author = {Heal, KR and Qin, W and Amin, SA and Devol, AH and Moffett, JW and Armbrust, EV and Stahl, DA and Ingalls, AE}, title = {Accumulation of NO2 -cobalamin in nutrient-stressed ammonia-oxidizing archaea and in the oxygen deficient zone of the eastern tropical North Pacific.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {453-457}, doi = {10.1111/1758-2229.12664}, pmid = {30022612}, issn = {1758-2229}, abstract = {Cobalamin (vitamin B12) is a precious resource in natural systems that is produced by select prokaryotes and required by a broad range of organisms. In this way, the production of cobalamin reinforces numerous microbial interdependencies. Here we report the accumulation of an unusual form of cobalamin, nitrocobalamin (NO2 -cobalamin), in a marine oxygen deficient zone (ODZ), isolates of ammonia-oxidizing archaea (AOA), and an anaerobic ammonium-oxidizing (anammox) bacteria enriched bioreactor. Low oxygen waters were enriched in NO2 -cobalamin, and AOA isolates experiencing ammonia or copper stress produced more NO2 -cobalamin, though there is wide strain-to-strain and batch-to-batch variability. NO2 -cobalamin has no known biochemical role. We hypothesize that AOA and anammox bacteria are a source of marine NO2 -cobalamin in the environment via a reactive nitrogen intermediate. These findings suggest connections between cobalamin forms and nitrogen transformations, physiological stress and ocean deoxygenation.}, } @article {pmid30022610, year = {2018}, author = {Di Cesare, A and Petrin, S and Fontaneto, D and Losasso, C and Eckert, EM and Tassistro, G and Borello, A and Ricci, A and Wilson, WH and Pruzzo, C and Vezzulli, L}, title = {ddPCR applied on archived Continuous Plankton Recorder samples reveals long-term occurrence of class 1 integrons and a sulphonamide resistance gene in marine plankton communities.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {458-464}, doi = {10.1111/1758-2229.12665}, pmid = {30022610}, issn = {1758-2229}, abstract = {Antibiotic resistance is a rising threat for human health. Although in clinical settings and terrestrial environments the rise of antibiotic resistant bacteria is well documented, their dissemination and spread in the marine environment, covering almost two-thirds of the Earth's surface, is still poorly understood. In this study, the presence and abundance of sulphonamide resistance gene (sul2) and class 1 integron-integrase gene (intI1), used as markers for the occurrence and spread of antibiotic resistance genes since the beginning of the antibiotic era, were investigated. Twenty-nine archived formalin-fixed samples, collected by the Continuous Plankton Recorder (CPR) survey in the Atlantic Ocean and North Sea from 1970 to 2011, were analysed using Droplet Digital PCR (ddPCR) applied for the first time on CPR samples. The two marker genes were present in a large fraction of the samples (48% for sul2 and 76% for intI1). In contrast, results from Real-Time PCR performed on the same samples greatly underestimate their occurrence (21% for sul2 and 52% for intI1). Overall, besides providing successful use of ddPCR for the molecular analysis of CPR samples, this study reveals long-term occurrence and spread of sul2 gene and class 1 integrons in the plankton-associated bacterial communities in the ocean.}, } @article {pmid30022608, year = {2018}, author = {Xie, C and Sun, K and Zhang, K and Sun, Y and Lu, Z}, title = {Cyanobacterial blooms in oil-contaminated subtidal sediments revealed by integrated approaches.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {444-452}, doi = {10.1111/1758-2229.12660}, pmid = {30022608}, issn = {1758-2229}, abstract = {Cyanobacteria are important primary producers on the surface of oceans and are susceptible to oil spills. However, their tolerance to oil and their roles in the bioremediation of crude oil remain elusive. We analysed the response of microbial communities to a simulated oil spill in estuarine sediment microcosms under a series of oil concentrations (0, 25, 125, and 250 g kg-1 dry wt.). Cyanobacterial blooms only occurred on the sediment surface in the low oil (LO, 25 g kg-1 dry wt.) group, and cyanobacteria grew from very small amounts to enriched levels according to an internal mechanism. The dominant phylotypes enriched in the oil-contaminated sediments on day 35 were Leptolyngbya, Oscillatoria, Arthrospira (Spirulina), Geitlerinema and Cyanothece, and the majority were capable of fixing nitrogen. Gammaproteobacterial blooms occurred during the early stage, and Oceanospirillales dominated the sediment surface. The annotation of unassembled metatranscriptomic data revealed an increase in nitrogen metabolism, particularly photosynthesis (antenna proteins) during the later stage, together with depletion of fatty acid metabolism. In summary, high concentrations of crude oil are toxic to cyanobacteria but can facilitate the emergence of cyanobacterial aggregation at low concentrations (crude oil concentration < 25 g kg-1 dry wt.).}, } @article {pmid30022580, year = {2018}, author = {Samo, TJ and Kimbrel, JA and Nilson, DJ and Pett-Ridge, J and Weber, PK and Mayali, X}, title = {Attachment between heterotrophic bacteria and microalgae influences symbiotic microscale interactions.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4385-4400}, doi = {10.1111/1462-2920.14357}, pmid = {30022580}, issn = {1462-2920}, support = {SCW1039//Department of Energy's Genome Sciences Program/ ; AC52-07NA27344//Lawrence Livermore National Laboratory/ ; //Texas A&M University/ ; }, abstract = {The surface and surroundings of microalgal cells (phycosphere) are critical interaction zones but have been difficult to functionally interrogate due to methodological limitations. We examined effects of phycosphere-associated bacteria for two biofuel-relevant microalgal species (Phaeodactylum tricornutum and Nannochloropsis salina) using stable isotope tracing and high spatial resolution mass spectrometry imaging (NanoSIMS) to quantify elemental exchanges at the single-cell level. Each algal species responded differently to bacterial attachment. In P. tricornutum, a high percentage of cells had attached bacteria (92%-98%, up to eight bacteria per alga) and fixed 64% more carbon with attached bacteria compared to axenic cells. In contrast, N. salina cells were less commonly associated with bacteria (42%-63%), harboured fewer bacteria per alga, and fixed 10% more carbon without attached bacteria compared to axenic cells. An uncultivated bacterium related to Haliscomenobacter sp. was identified as an effective mutualist; it increased carbon fixation when attached to P. tricornutum and incorporated 71% more algal-fixed carbon relative to other bacteria. Our results illustrate how phylogenetic identity and physical location of bacteria and algae facilitate diverse metabolic responses. Phycosphere-mediated, mutualistic chemical exchanges between autotrophs and heterotrophs may be a fruitful means to increase microalgal productivity for applied engineering efforts.}, } @article {pmid30022295, year = {2018}, author = {Subramanian, A and Sarkar, RR}, title = {Evolutionary Perspectives of Genotype-Phenotype Factors in Leishmania Metabolism.}, journal = {Journal of molecular evolution}, volume = {86}, number = {7}, pages = {443-456}, pmid = {30022295}, issn = {1432-1432}, support = {BT/PR14958/BID/7/537/2015//Department of Biotechnology, Government of India/ ; Senior Research Fellowship from DBT-BINC//Department of Biotechnology, Government of India/ ; }, abstract = {The sandfly midgut and the human macrophage phagolysosome provide antagonistic metabolic niches for the endoparasite Leishmania to survive and populate. Although these environments fluctuate across developmental stages, the relative changes in both these environments across parasite generations might remain gradual. Such environmental restrictions might endow parasite metabolism with a choice of specific genotypic and phenotypic factors that can constrain enzyme evolution for successful adaptation to the host. With respect to the available cellular information for Leishmania species, for the first time, we measure the relative contribution of eight inter-correlated predictors related to codon usage, GC content, gene expression, gene length, multi-functionality, and flux-coupling potential of an enzyme on the evolutionary rates of singleton metabolic genes and further compare their effects across three Leishmania species. Our analysis reveals that codon adaptation, multi-functionality, and flux-coupling potential of an enzyme are independent contributors of enzyme evolutionary rates, which can together explain a large variation in enzyme evolutionary rates across species. We also hypothesize that a species-specific occurrence of duplicated genes in novel subcellular locations can create new flux routes through certain singleton flux-coupled enzymes, thereby constraining their evolution. A cross-species comparison revealed both common and species-specific genes whose evolutionary divergence was constrained by multiple independent factors. Out of these, previously known pharmacological targets and virulence factors in Leishmania were identified, suggesting their evolutionary reasons for being important survival factors to the parasite. All these results provide a fundamental understanding of the factors underlying adaptive strategies of the parasite, which can be further targeted.}, } @article {pmid30022168, year = {2018}, author = {Noordermeer, SM and Adam, S and Setiaputra, D and Barazas, M and Pettitt, SJ and Ling, AK and Olivieri, M and Álvarez-Quilón, A and Moatti, N and Zimmermann, M and Annunziato, S and Krastev, DB and Song, F and Brandsma, I and Frankum, J and Brough, R and Sherker, A and Landry, S and Szilard, RK and Munro, MM and McEwan, A and Goullet de Rugy, T and Lin, ZY and Hart, T and Moffat, J and Gingras, AC and Martin, A and van Attikum, H and Jonkers, J and Lord, CJ and Rottenberg, S and Durocher, D}, title = {The shieldin complex mediates 53BP1-dependent DNA repair.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {117-121}, pmid = {30022168}, issn = {1476-4687}, support = {156869//Swiss National Science Foundation/Switzerland ; 319661//European Research Council/International ; }, mesh = {Animals ; CRISPR-Cas Systems ; Cell Line ; DNA Breaks, Double-Stranded ; *DNA Repair ; DNA, Single-Stranded/genetics ; Female ; Genes, BRCA1 ; Humans ; Immunoglobulin Class Switching/genetics ; Mice ; Models, Biological ; Multiprotein Complexes/chemistry/deficiency/genetics/*metabolism ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Telomere-Binding Proteins/metabolism ; Tumor Suppressor Protein p53/deficiency ; Tumor Suppressor p53-Binding Protein 1/*metabolism ; }, abstract = {53BP1 is a chromatin-binding protein that regulates the repair of DNA double-strand breaks by suppressing the nucleolytic resection of DNA termini1,2. This function of 53BP1 requires interactions with PTIP3 and RIF14-9, the latter of which recruits REV7 (also known as MAD2L2) to break sites10,11. How 53BP1-pathway proteins shield DNA ends is currently unknown, but there are two models that provide the best potential explanation of their action. In one model the 53BP1 complex strengthens the nucleosomal barrier to end-resection nucleases12,13, and in the other 53BP1 recruits effector proteins with end-protection activity. Here we identify a 53BP1 effector complex, shieldin, that includes C20orf196 (also known as SHLD1), FAM35A (SHLD2), CTC-534A2.2 (SHLD3) and REV7. Shieldin localizes to double-strand-break sites in a 53BP1- and RIF1-dependent manner, and its SHLD2 subunit binds to single-stranded DNA via OB-fold domains that are analogous to those of RPA1 and POT1. Loss of shieldin impairs non-homologous end-joining, leads to defective immunoglobulin class switching and causes hyper-resection. Mutations in genes that encode shieldin subunits also cause resistance to poly(ADP-ribose) polymerase inhibition in BRCA1-deficient cells and tumours, owing to restoration of homologous recombination. Finally, we show that binding of single-stranded DNA by SHLD2 is critical for shieldin function, consistent with a model in which shieldin protects DNA ends to mediate 53BP1-dependent DNA repair.}, } @article {pmid30022167, year = {2018}, author = {Gu, Y and Alt, EA and Wang, H and Li, X and Willard, AP and Johnson, JA}, title = {Photoswitching topology in polymer networks with metal-organic cages as crosslinks.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {65-69}, doi = {10.1038/s41586-018-0339-0}, pmid = {30022167}, issn = {1476-4687}, support = {CHE-1629358//National Science Foundation/International ; CHE-1506722//National Science Foundation/International ; }, abstract = {Polymer networks can have a range of desirable properties such as mechanical strength, wide compositional diversity between different materials, permanent porosity, convenient processability and broad solvent compatibility1,2. Designing polymer networks from the bottom up with new structural motifs and chemical compositions can be used to impart dynamic features such as malleability or self-healing, or to allow the material to respond to environmental stimuli3-8. However, many existing systems exhibit only one operational state that is defined by the material's composition and topology3-6; or their responsiveness may be irreversible7,9,10 and limited to a single network property11,12 (such as stiffness). Here we use cooperative self-assembly as a design principle to prepare a material that can be switched between two topological states. By using networks of polymer-linked metal-organic cages in which the cages change shape and size on irradiation, we can reversibly switch the network topology with ultraviolet or green light. This photoswitching produces coherent changes in several network properties at once, including branch functionality, junction fluctuations, defect tolerance, shear modulus, stress-relaxation behaviour and self-healing. Topology-switching materials could prove useful in fields such as soft robotics and photo-actuators as well as providing model systems for fundamental polymer physics studies.}, } @article {pmid30022166, year = {2018}, author = {Yao, H and Price, TT and Cantelli, G and Ngo, B and Warner, MJ and Olivere, L and Ridge, SM and Jablonski, EM and Therrien, J and Tannheimer, S and McCall, CM and Chenn, A and Sipkins, DA}, title = {Leukaemia hijacks a neural mechanism to invade the central nervous system.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {55-60}, doi = {10.1038/s41586-018-0342-5}, pmid = {30022166}, issn = {1476-4687}, mesh = {Animals ; Antibodies, Neutralizing/immunology ; Basement Membrane/metabolism ; Blood-Brain Barrier/metabolism ; Bone Marrow ; Cell Movement ; Central Nervous System/blood supply/metabolism/*pathology ; Cerebrospinal Fluid/metabolism ; Cerebrovascular Circulation ; Class I Phosphatidylinositol 3-Kinases/antagonists & inhibitors ; Disease Progression ; Female ; Heterografts/immunology/pathology ; Integrin alpha6/immunology/metabolism ; Laminin/metabolism ; Male ; Mice ; Mice, SCID ; Neoplasm Transplantation ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/enzymology/metabolism/*pathology ; Receptors, Laminin/antagonists & inhibitors/immunology/metabolism ; Skull ; Subarachnoid Space ; }, abstract = {Acute lymphoblastic leukaemia (ALL) has a marked propensity to metastasize to the central nervous system (CNS). In contrast to brain metastases from solid tumours, metastases of ALL seldom involve the parenchyma but are isolated to the leptomeninges, which is an infrequent site for carcinomatous invasion. Although metastasis to the CNS occurs across all subtypes of ALL, a unifying mechanism for invasion has not yet been determined. Here we show that ALL cells in the circulation are unable to breach the blood-brain barrier in mice; instead, they migrate into the CNS along vessels that pass directly between vertebral or calvarial bone marrow and the subarachnoid space. The basement membrane of these bridging vessels is enriched in laminin, which is known to coordinate pathfinding of neuronal progenitor cells in the CNS. The laminin receptor α6 integrin is expressed in most cases of ALL. We found that α6 integrin-laminin interactions mediated the migration of ALL cells towards the cerebrospinal fluid in vitro. Mice with ALL xenografts were treated with either a PI3Kδ inhibitor, which decreased α6 integrin expression on ALL cells, or specific α6 integrin-neutralizing antibodies and showed significant reductions in ALL transit along bridging vessels, blast counts in the cerebrospinal fluid and CNS disease symptoms despite minimally decreased bone marrow disease burden. Our data suggest that α6 integrin expression, which is common in ALL, allows cells to use neural migratory pathways to invade the CNS.}, } @article {pmid30022165, year = {2018}, author = {Wan, X and Zinselmeyer, BH and Zakharov, PN and Vomund, AN and Taniguchi, R and Santambrogio, L and Anderson, MS and Lichti, CF and Unanue, ER}, title = {Pancreatic islets communicate with lymphoid tissues via exocytosis of insulin peptides.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {107-111}, pmid = {30022165}, issn = {1476-4687}, support = {R01 AI114551/AI/NIAID NIH HHS/United States ; R01 DK058177/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Animals ; Antigen Presentation/immunology ; Cytoplasmic Granules/chemistry/drug effects/metabolism ; Epitopes/immunology ; *Exocytosis/drug effects ; Female ; Glucose/metabolism/pharmacology ; Humans ; Insulin/blood/chemistry/immunology/*metabolism ; Islets of Langerhans/*cytology/drug effects/*metabolism ; Lymphoid Tissue/cytology/drug effects/immunology/*metabolism ; Male ; Mice, Inbred NOD ; Middle Aged ; Peptide Fragments/blood/chemistry/immunology/*metabolism ; Phenotype ; T-Lymphocytes/drug effects/immunology ; }, abstract = {Tissue-specific autoimmunity occurs when selected antigens presented by susceptible alleles of the major histocompatibility complex are recognized by T cells. However, the reason why certain specific self-antigens dominate the response and are indispensable for triggering autoreactivity is unclear. Spontaneous presentation of insulin is essential for initiating autoimmune type 1 diabetes in non-obese diabetic mice1,2. A major set of pathogenic CD4 T cells specifically recognizes the 12-20 segment of the insulin B-chain (B:12-20), an epitope that is generated from direct presentation of insulin peptides by antigen-presenting cells3,4. These T cells do not respond to antigen-presenting cells that have taken up insulin that, after processing, leads to presentation of a different segment representing a one-residue shift, B:13-214. CD4 T cells that recognize B:12-20 escape negative selection in the thymus and cause diabetes, whereas those that recognize B:13-21 have only a minor role in autoimmunity3-5. Although presentation of B:12-20 is evident in the islets3,6, insulin-specific germinal centres can be formed in various lymphoid tissues, suggesting that insulin presentation is widespread7,8. Here we use live imaging to document the distribution of insulin recognition by CD4 T cells throughout various lymph nodes. Furthermore, we identify catabolized insulin peptide fragments containing defined pathogenic epitopes in β-cell granules from mice and humans. Upon glucose challenge, these fragments are released into the circulation and are recognized by CD4 T cells, leading to an activation state that results in transcriptional reprogramming and enhanced diabetogenicity. Therefore, a tissue such as pancreatic islets, by releasing catabolized products, imposes a constant threat to self-tolerance. These findings reveal a self-recognition pathway underlying a primary autoantigen and provide a foundation for assessing antigenic targets that precipitate pathogenic outcomes by systemically sensitizing lymphoid tissues.}, } @article {pmid30022164, year = {2018}, author = {Miller, CN and Proekt, I and von Moltke, J and Wells, KL and Rajpurkar, AR and Wang, H and Rattay, K and Khan, IS and Metzger, TC and Pollack, JL and Fries, AC and Lwin, WW and Wigton, EJ and Parent, AV and Kyewski, B and Erle, DJ and Hogquist, KA and Steinmetz, LM and Locksley, RM and Anderson, MS}, title = {Thymic tuft cells promote an IL-4-enriched medulla and shape thymocyte development.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {627-631}, pmid = {30022164}, issn = {1476-4687}, support = {P30 DK063720/DK/NIDDK NIH HHS/United States ; R37 AI039560/AI/NIAID NIH HHS/United States ; R01 AI097457/AI/NIAID NIH HHS/United States ; T32 GM007790/GM/NIGMS NIH HHS/United States ; R37 AI097457/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cellular Microenvironment ; Epithelial Cells/*cytology/*metabolism ; Female ; Humans ; Immune Tolerance/immunology ; Interleukin-4/biosynthesis/*metabolism ; Interleukins/metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Protein-Serine-Threonine Kinases/metabolism ; TRPM Cation Channels/metabolism ; Thymocytes/*cytology/metabolism ; Thymus Gland/anatomy & histology/*cytology/*metabolism ; Transcription Factors/deficiency/genetics ; }, abstract = {The thymus is responsible for generating a diverse yet self-tolerant pool of T cells1. Although the thymic medulla consists mostly of developing and mature AIRE+ epithelial cells, recent evidence has suggested that there is far greater heterogeneity among medullary thymic epithelial cells than was previously thought2. Here we describe in detail an epithelial subset that is remarkably similar to peripheral tuft cells that are found at mucosal barriers3. Similar to the periphery, thymic tuft cells express the canonical taste transduction pathway and IL-25. However, they are unique in their spatial association with cornified aggregates, ability to present antigens and expression of a broad diversity of taste receptors. Some thymic tuft cells pass through an Aire-expressing stage and depend on a known AIRE-binding partner, HIPK2, for their development. Notably, the taste chemosensory protein TRPM5 is required for their thymic function through which they support the development and polarization of thymic invariant natural killer T cells and act to establish a medullary microenvironment that is enriched in the type 2 cytokine, IL-4. These findings indicate that there is a compartmentalized medullary environment in which differentiation of a minor and highly specialized epithelial subset has a non-redundant role in shaping thymic function.}, } @article {pmid30022163, year = {2018}, author = {Crockford, PW and Hayles, JA and Bao, H and Planavsky, NJ and Bekker, A and Fralick, PW and Halverson, GP and Bui, TH and Peng, Y and Wing, BA}, title = {Triple oxygen isotope evidence for limited mid-Proterozoic primary productivity.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {613-616}, doi = {10.1038/s41586-018-0349-y}, pmid = {30022163}, issn = {1476-4687}, mesh = {Atmosphere/chemistry ; Carbon Dioxide/analysis ; *Ecosystem ; Geologic Sediments/*chemistry/*microbiology ; History, Ancient ; Ontario ; Oxygen/*analysis/*metabolism ; Oxygen Isotopes/analysis/metabolism ; Partial Pressure ; Photosynthesis ; Probability ; Sulfates/analysis/metabolism ; Sulfides/analysis/metabolism ; Sulfur/*analysis/*metabolism ; Sulfur Isotopes/analysis/metabolism ; }, abstract = {The global biosphere is commonly assumed to have been less productive before the rise of complex eukaryotic ecosystems than it is today1. However, direct evidence for this assertion is lacking. Here we present triple oxygen isotope measurements (∆17O) from sedimentary sulfates from the Sibley basin (Ontario, Canada) dated to about 1.4 billion years ago, which provide evidence for a less productive biosphere in the middle of the Proterozoic eon. We report what are, to our knowledge, the most-negative ∆17O values (down to -0.88‰) observed in sulfates, except for those from the terminal Cryogenian period2. This observation demonstrates that the mid-Proterozoic atmosphere was distinct from what persisted over approximately the past 0.5 billion years, directly reflecting a unique interplay among the atmospheric partial pressures of CO2 and O2 and the photosynthetic O2 flux at this time3. Oxygenic gross primary productivity is stoichiometrically related to the photosynthetic O2 flux to the atmosphere. Under current estimates of mid-Proterozoic atmospheric partial pressure of CO2 (2-30 times that of pre-anthropogenic levels), our modelling indicates that gross primary productivity was between about 6% and 41% of pre-anthropogenic levels if atmospheric O2 was between 0.1-1% or 1-10% of pre-anthropogenic levels, respectively. When compared to estimates of Archaean4-6 and Phanerozoic primary production7, these model solutions show that an increasingly more productive biosphere accompanied the broad secular pattern of increasing atmospheric O2 over geologic time8.}, } @article {pmid30022162, year = {2018}, author = {Bornstein, C and Nevo, S and Giladi, A and Kadouri, N and Pouzolles, M and Gerbe, F and David, E and Machado, A and Chuprin, A and Tóth, B and Goldberg, O and Itzkovitz, S and Taylor, N and Jay, P and Zimmermann, VS and Abramson, J and Amit, I}, title = {Single-cell mapping of the thymic stroma identifies IL-25-producing tuft epithelial cells.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {622-626}, doi = {10.1038/s41586-018-0346-1}, pmid = {30022162}, issn = {1476-4687}, mesh = {Animals ; Epigenesis, Genetic ; Epithelial Cells/*cytology/immunology/*metabolism ; Female ; Humans ; Interleukin-17/biosynthesis/*metabolism ; Interleukins/biosynthesis/*metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Models, Molecular ; *Single-Cell Analysis ; Thymus Gland/*cytology/*immunology ; Transcription Factors/biosynthesis/deficiency/genetics/metabolism ; }, abstract = {T cell development and selection are coordinated in the thymus by a specialized niche of diverse stromal populations1-3. Although much progress has been made over the years in identifying the functions of the different cell types of the thymic stromal compartment, there is no comprehensive characterization of their diversity and heterogeneity. Here we combined massively parallel single-cell RNA-sequencing4,5, spatial mapping, chromatin profiling and gene targeting to characterize de novo the entire stromal compartment of the mouse thymus. We identified dozens of cell states, with thymic epithelial cells (TECs) showing the highest degree of heterogeneity. Our analysis highlights four major medullary TEC (mTEC I-IV) populations, with distinct molecular functions, epigenetic landscapes and lineage regulators. Specifically, mTEC IV constitutes a new and highly divergent TEC lineage with molecular characteristics of the gut chemosensory epithelial tuft cells. Mice deficient in Pou2f3, a master regulator of tuft cells, have complete and specific depletion of mTEC IV cells, which results in increased levels of thymus-resident type-2 innate lymphoid cells. Overall, our study provides a comprehensive characterization of the thymic stroma and identifies a new tuft-like TEC population, which is critical for shaping the immune niche in the thymus.}, } @article {pmid30022161, year = {2018}, author = {Wu, D and Hu, D and Chen, H and Shi, G and Fetahu, IS and Wu, F and Rabidou, K and Fang, R and Tan, L and Xu, S and Liu, H and Argueta, C and Zhang, L and Mao, F and Yan, G and Chen, J and Dong, Z and Lv, R and Xu, Y and Wang, M and Ye, Y and Zhang, S and Duquette, D and Geng, S and Yin, C and Lian, CG and Murphy, GF and Adler, GK and Garg, R and Lynch, L and Yang, P and Li, Y and Lan, F and Fan, J and Shi, Y and Shi, YG}, title = {Glucose-regulated phosphorylation of TET2 by AMPK reveals a pathway linking diabetes to cancer.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {637-641}, doi = {10.1038/s41586-018-0350-5}, pmid = {30022161}, issn = {1476-4687}, support = {R01 CA194302/CA/NCI NIH HHS/United States ; R01 GM112062/GM/NIGMS NIH HHS/United States ; GM112062/NH/NIH HHS/United States ; CA194302/NH/NIH HHS/United States ; }, abstract = {Diabetes is a complex metabolic syndrome that is characterized by prolonged high blood glucose levels and frequently associated with life-threatening complications1,2. Epidemiological studies have suggested that diabetes is also linked to an increased risk of cancer3-5. High glucose levels may be a prevailing factor that contributes to the link between diabetes and cancer, but little is known about the molecular basis of this link and how the high glucose state may drive genetic and/or epigenetic alterations that result in a cancer phenotype. Here we show that hyperglycaemic conditions have an adverse effect on the DNA 5-hydroxymethylome. We identify the tumour suppressor TET2 as a substrate of the AMP-activated kinase (AMPK), which phosphorylates TET2 at serine 99, thereby stabilizing the tumour suppressor. Increased glucose levels impede AMPK-mediated phosphorylation at serine 99, which results in the destabilization of TET2 followed by dysregulation of both 5-hydroxymethylcytosine (5hmC) and the tumour suppressive function of TET2 in vitro and in vivo. Treatment with the anti-diabetic drug metformin protects AMPK-mediated phosphorylation of serine 99, thereby increasing TET2 stability and 5hmC levels. These findings define a novel 'phospho-switch' that regulates TET2 stability and a regulatory pathway that links glucose and AMPK to TET2 and 5hmC, which connects diabetes to cancer. Our data also unravel an epigenetic pathway by which metformin mediates tumour suppression. Thus, this study presents a new model for how a pernicious environment can directly reprogram the epigenome towards an oncogenic state, offering a potential strategy for cancer prevention and treatment.}, } @article {pmid30022160, year = {2018}, author = {Rojas, ER and Billings, G and Odermatt, PD and Auer, GK and Zhu, L and Miguel, A and Chang, F and Weibel, DB and Theriot, JA and Huang, KC}, title = {The outer membrane is an essential load-bearing element in Gram-negative bacteria.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {617-621}, pmid = {30022160}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; P50 GM107615/GM/NIGMS NIH HHS/United States ; R01 GM056836/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Membrane/drug effects/*metabolism ; Cell Wall/drug effects/*metabolism ; Detergents/pharmacology ; Escherichia coli/cytology/drug effects/metabolism ; Gram-Negative Bacteria/*cytology/drug effects/*metabolism ; Microbial Viability/drug effects ; Weight-Bearing ; }, abstract = {Gram-negative bacteria possess a complex cell envelope that consists of a plasma membrane, a peptidoglycan cell wall and an outer membrane. The envelope is a selective chemical barrier1 that defines cell shape2 and allows the cell to sustain large mechanical loads such as turgor pressure3. It is widely believed that the covalently cross-linked cell wall underpins the mechanical properties of the envelope4,5. Here we show that the stiffness and strength of Escherichia coli cells are largely due to the outer membrane. Compromising the outer membrane, either chemically or genetically, greatly increased deformation of the cell envelope in response to stretching, bending and indentation forces, and induced increased levels of cell lysis upon mechanical perturbation and during L-form proliferation. Both lipopolysaccharides and proteins contributed to the stiffness of the outer membrane. These findings overturn the prevailing dogma that the cell wall is the dominant mechanical element within Gram-negative bacteria, instead demonstrating that the outer membrane can be stiffer than the cell wall, and that mechanical loads are often balanced between these structures.}, } @article {pmid30022159, year = {2018}, author = {Mills, EL and Pierce, KA and Jedrychowski, MP and Garrity, R and Winther, S and Vidoni, S and Yoneshiro, T and Spinelli, JB and Lu, GZ and Kazak, L and Banks, AS and Haigis, MC and Kajimura, S and Murphy, MP and Gygi, SP and Clish, CB and Chouchani, ET}, title = {Accumulation of succinate controls activation of adipose tissue thermogenesis.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {102-106}, doi = {10.1038/s41586-018-0353-2}, pmid = {30022159}, issn = {1476-4687}, support = {R01 DK103295/DK/NIDDK NIH HHS/United States ; R01 DK112268/DK/NIDDK NIH HHS/United States ; R01 GM067945/GM/NIGMS NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; 110159/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adipocytes/drug effects/enzymology/metabolism ; Adipose Tissue, Brown/cytology/drug effects/enzymology/*metabolism ; Adipose Tissue, White/cytology/drug effects/enzymology/metabolism ; Animals ; Female ; Male ; Metabolomics ; Mice ; Obesity/metabolism/prevention & control ; Oxidation-Reduction/drug effects ; Reactive Oxygen Species/metabolism ; Succinate Dehydrogenase/metabolism ; Succinic Acid/*metabolism/pharmacology ; Thermogenesis/drug effects/*physiology ; Uncoupling Protein 1/metabolism ; }, abstract = {Thermogenesis by brown and beige adipose tissue, which requires activation by external stimuli, can counter metabolic disease1. Thermogenic respiration is initiated by adipocyte lipolysis through cyclic AMP-protein kinase A signalling; this pathway has been subject to longstanding clinical investigation2-4. Here we apply a comparative metabolomics approach and identify an independent metabolic pathway that controls acute activation of adipose tissue thermogenesis in vivo. We show that substantial and selective accumulation of the tricarboxylic acid cycle intermediate succinate is a metabolic signature of adipose tissue thermogenesis upon activation by exposure to cold. Succinate accumulation occurs independently of adrenergic signalling, and is sufficient to elevate thermogenic respiration in brown adipocytes. Selective accumulation of succinate may be driven by a capacity of brown adipocytes to sequester elevated circulating succinate. Furthermore, brown adipose tissue thermogenesis can be initiated by systemic administration of succinate in mice. Succinate from the extracellular milieu is rapidly metabolized by brown adipocytes, and its oxidation by succinate dehydrogenase is required for activation of thermogenesis. We identify a mechanism whereby succinate dehydrogenase-mediated oxidation of succinate initiates production of reactive oxygen species, and drives thermogenic respiration, whereas inhibition of succinate dehydrogenase supresses thermogenesis. Finally, we show that pharmacological elevation of circulating succinate drives UCP1-dependent thermogenesis by brown adipose tissue in vivo, which stimulates robust protection against diet-induced obesity and improves glucose tolerance. These findings reveal an unexpected mechanism for control of thermogenesis, using succinate as a systemically-derived thermogenic molecule.}, } @article {pmid30022158, year = {2018}, author = {Mirman, Z and Lottersberger, F and Takai, H and Kibe, T and Gong, Y and Takai, K and Bianchi, A and Zimmermann, M and Durocher, D and de Lange, T}, title = {53BP1-RIF1-shieldin counteracts DSB resection through CST- and Polα-dependent fill-in.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {112-116}, pmid = {30022158}, issn = {1476-4687}, support = {R35 CA210036/CA/NCI NIH HHS/United States ; T32 GM066699/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; BRCA1 Protein/deficiency ; Cell Line ; *DNA Breaks, Double-Stranded ; DNA Polymerase I/*metabolism ; DNA Primase/metabolism ; DNA, Single-Stranded/genetics/metabolism ; Humans ; Mice ; Multiprotein Complexes/*chemistry/*metabolism ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors ; Recombinational DNA Repair ; Telomere/genetics/metabolism ; Telomere-Binding Proteins/*metabolism ; Tumor Suppressor p53-Binding Protein 1/*metabolism ; }, abstract = {In DNA repair, the resection of double-strand breaks dictates the choice between homology-directed repair-which requires a 3' overhang-and classical non-homologous end joining, which can join unresected ends1,2. BRCA1-mutant cancers show minimal resection of double-strand breaks, which renders them deficient in homology-directed repair and sensitive to inhibitors of poly(ADP-ribose) polymerase 1 (PARP1)3-8. When BRCA1 is absent, the resection of double-strand breaks is thought to be prevented by 53BP1, RIF1 and the REV7-SHLD1-SHLD2-SHLD3 (shieldin) complex, and loss of these factors diminishes sensitivity to PARP1 inhibitors4,6-9. Here we address the mechanism by which 53BP1-RIF1-shieldin regulates the generation of recombinogenic 3' overhangs. We report that CTC1-STN1-TEN1 (CST)10, a complex similar to replication protein A that functions as an accessory factor of polymerase-α (Polα)-primase11, is a downstream effector in the 53BP1 pathway. CST interacts with shieldin and localizes with Polα to sites of DNA damage in a 53BP1- and shieldin-dependent manner. As with loss of 53BP1, RIF1 or shieldin, the depletion of CST leads to increased resection. In BRCA1-deficient cells, CST blocks RAD51 loading and promotes the efficacy of PARP1 inhibitors. In addition, Polα inhibition diminishes the effect of PARP1 inhibitors. These data suggest that CST-Polα-mediated fill-in helps to control the repair of double-strand breaks by 53BP1, RIF1 and shieldin.}, } @article {pmid30022143, year = {2018}, author = {}, title = {Turtle trouble, fund fraud and India's escape module.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {306-307}, doi = {10.1038/d41586-018-05705-w}, pmid = {30022143}, issn = {1476-4687}, } @article {pmid30022142, year = {2018}, author = {}, title = {Officials and scientists need help to track down rogue source of CFCs.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {302}, doi = {10.1038/d41586-018-05743-4}, pmid = {30022142}, issn = {1476-4687}, } @article {pmid30022141, year = {2018}, author = {}, title = {Track the fate of postdocs to help the next generation of scientists.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {302}, doi = {10.1038/d41586-018-05745-2}, pmid = {30022141}, issn = {1476-4687}, } @article {pmid30022140, year = {2018}, author = {Fan, ZH}, title = {Learn from industry to build a healthy lab.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {331}, doi = {10.1038/d41586-018-05748-z}, pmid = {30022140}, issn = {1476-4687}, } @article {pmid30022139, year = {2018}, author = {Tang, L and Hu, G}, title = {Evaluation woes: Metrics can help beat bias.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {331}, doi = {10.1038/d41586-018-05751-4}, pmid = {30022139}, issn = {1476-4687}, } @article {pmid30022138, year = {2018}, author = {Akhondzadeh, S}, title = {Iran's scientists uncrushed by decades of sanctions.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {331}, doi = {10.1038/d41586-018-05747-0}, pmid = {30022138}, issn = {1476-4687}, } @article {pmid30022137, year = {2018}, author = {Zaratin, P and Salvetti, M}, title = {Evaluation woes: define metrics from the off.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {331}, doi = {10.1038/d41586-018-05750-5}, pmid = {30022137}, issn = {1476-4687}, } @article {pmid30022136, year = {2018}, author = {Sciortino, F}, title = {Why organizing a scientific conference can produce huge benefits.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {431}, doi = {10.1038/d41586-018-05714-9}, pmid = {30022136}, issn = {1476-4687}, } @article {pmid30022135, year = {2018}, author = {Beattie, A}, title = {Evaluation woes: professors should have fought harder.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {331}, doi = {10.1038/d41586-018-05749-y}, pmid = {30022135}, issn = {1476-4687}, } @article {pmid30022134, year = {2018}, author = {Rodenburg, J}, title = {A record-breaking microscope.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {334-335}, doi = {10.1038/d41586-018-05711-y}, pmid = {30022134}, issn = {1476-4687}, } @article {pmid30022133, year = {2018}, author = {Granda, JM and Donina, L and Dragone, V and Long, DL and Cronin, L}, title = {Controlling an organic synthesis robot with machine learning to search for new reactivity.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {377-381}, pmid = {30022133}, issn = {1476-4687}, support = {670467//European Research Council/International ; }, abstract = {The discovery of chemical reactions is an inherently unpredictable and time-consuming process1. An attractive alternative is to predict reactivity, although relevant approaches, such as computer-aided reaction design, are still in their infancy2. Reaction prediction based on high-level quantum chemical methods is complex3, even for simple molecules. Although machine learning is powerful for data analysis4,5, its applications in chemistry are still being developed6. Inspired by strategies based on chemists' intuition7, we propose that a reaction system controlled by a machine learning algorithm may be able to explore the space of chemical reactions quickly, especially if trained by an expert8. Here we present an organic synthesis robot that can perform chemical reactions and analysis faster than they can be performed manually, as well as predict the reactivity of possible reagent combinations after conducting a small number of experiments, thus effectively navigating chemical reaction space. By using machine learning for decision making, enabled by binary encoding of the chemical inputs, the reactions can be assessed in real time using nuclear magnetic resonance and infrared spectroscopy. The machine learning system was able to predict the reactivity of about 1,000 reaction combinations with accuracy greater than 80 per cent after considering the outcomes of slightly over 10 per cent of the dataset. This approach was also used to calculate the reactivity of published datasets. Further, by using real-time data from our robot, these predictions were followed up manually by a chemist, leading to the discovery of four reactions.}, } @article {pmid30022132, year = {2018}, author = {Chen, X and Tung, KK}, title = {Global surface warming enhanced by weak Atlantic overturning circulation.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {387-391}, doi = {10.1038/s41586-018-0320-y}, pmid = {30022132}, issn = {1476-4687}, abstract = {Evidence from palaeoclimatology suggests that abrupt Northern Hemisphere cold events are linked to weakening of the Atlantic Meridional Overturning Circulation (AMOC)1, potentially by excess inputs of fresh water2. But these insights-often derived from model runs under preindustrial conditions-may not apply to the modern era with our rapid emissions of greenhouse gases. If they do, then a weakened AMOC, as in 1975-1998, should have led to Northern Hemisphere cooling. Here we show that, instead, the AMOC minimum was a period of rapid surface warming. More generally, in the presence of greenhouse-gas heating, the AMOC's dominant role changed from transporting surface heat northwards, warming Europe and North America, to storing heat in the deeper Atlantic, buffering surface warming for the planet as a whole. During an accelerating phase from the mid-1990s to the early 2000s, the AMOC stored about half of excess heat globally, contributing to the global-warming slowdown. By contrast, since mooring observations began3-5 in 2004, the AMOC and oceanic heat uptake have weakened. Our results, based on several independent indices, show that AMOC changes since the 1940s are best explained by multidecadal variability6, rather than an anthropogenically forced trend. Leading indicators in the subpolar North Atlantic today suggest that the current AMOC decline is ending. We expect a prolonged AMOC minimum, probably lasting about two decades. If prior patterns hold, the resulting low levels of oceanic heat uptake will manifest as a period of rapid global surface warming.}, } @article {pmid30022131, year = {2018}, author = {Jiang, Y and Chen, Z and Han, Y and Deb, P and Gao, H and Xie, S and Purohit, P and Tate, MW and Park, J and Gruner, SM and Elser, V and Muller, DA}, title = {Electron ptychography of 2D materials to deep sub-ångström resolution.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {343-349}, doi = {10.1038/s41586-018-0298-5}, pmid = {30022131}, issn = {1476-4687}, abstract = {Aberration-corrected optics have made electron microscopy at atomic resolution a widespread and often essential tool for characterizing nanoscale structures. Image resolution has traditionally been improved by increasing the numerical aperture of the lens (α) and the beam energy, with the state-of-the-art at 300 kiloelectronvolts just entering the deep sub-ångström (that is, less than 0.5 ångström) regime. Two-dimensional (2D) materials are imaged at lower beam energies to avoid displacement damage from large momenta transfers, limiting spatial resolution to about 1 ångström. Here, by combining an electron microscope pixel-array detector with the dynamic range necessary to record the complete distribution of transmitted electrons and full-field ptychography to recover phase information from the full phase space, we increase the spatial resolution well beyond the traditional numerical-aperture-limited resolution. At a beam energy of 80 kiloelectronvolts, our ptychographic reconstruction improves the image contrast of single-atom defects in MoS2 substantially, reaching an information limit close to 5α, which corresponds to an Abbe diffraction-limited resolution of 0.39 ångström, at the electron dose and imaging conditions for which conventional imaging methods reach only 0.98 ångström.}, } @article {pmid30022114, year = {2018}, author = {Williams, MJ and Werner, B and Heide, T and Curtis, C and Barnes, CP and Sottoriva, A and Graham, TA}, title = {Author Correction: Quantification of subclonal selection in cancer from bulk sequencing data.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1342}, doi = {10.1038/s41588-018-0169-x}, pmid = {30022114}, issn = {1546-1718}, abstract = {In the version of this article originally published, in the "Theoretical framework of subclonal selection" section of the main text, ref. 11 instead of ref. 19 should have been cited at the end of the phrase "Our previously presented frequentist approach to detect subclonal selection from bulk sequencing data involves an R2 test statistic." The error has been corrected in the HTML and PDF versions of the article.}, } @article {pmid30022106, year = {2018}, author = {Trenkmann, M}, title = {Gold rush to gene-editing in the brain.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {532-533}, doi = {10.1038/s41576-018-0038-6}, pmid = {30022106}, issn = {1471-0064}, } @article {pmid30022105, year = {2018}, author = {Du, D and Wang-Kan, X and Neuberger, A and van Veen, HW and Pos, KM and Piddock, LJV and Luisi, BF}, title = {Author Correction: Multidrug efflux pumps: structure, function and regulation.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {577}, doi = {10.1038/s41579-018-0060-x}, pmid = {30022105}, issn = {1740-1534}, abstract = {In the version of this Review originally published, the author contributions of co-author Arthur Neuberger were incorrectly listed. The author contributions should have appeared as 'D.D., X.W.-K., A.N., H.W.v.V., K.M.P., L.J.V.P. and B.F.L. researched data for the article, made substantial contributions to discussions of the content, wrote the article, and reviewed and edited the manuscript before submission'. This has now been corrected in all versions of the Review. The authors apologize to readers for this error.}, } @article {pmid30022104, year = {2018}, author = {Hofer, U}, title = {Provoking your enemies to kill each other.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {520}, doi = {10.1038/s41579-018-0062-8}, pmid = {30022104}, issn = {1740-1534}, } @article {pmid30022103, year = {2018}, author = {Hofer, U}, title = {Feast and famine: the keys to gut engraftment.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {520}, doi = {10.1038/s41579-018-0061-9}, pmid = {30022103}, issn = {1740-1534}, } @article {pmid30021855, year = {2018}, author = {Lo Iacono, G and Cunningham, AA and Bett, B and Grace, D and Redding, DW and Wood, JLN}, title = {Environmental limits of Rift Valley fever revealed using ecoepidemiological mechanistic models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7448-E7456}, pmid = {30021855}, issn = {1091-6490}, support = {//Department of Health/United Kingdom ; MR/R02491X/1//Medical Research Council/United Kingdom ; }, mesh = {Aedes ; Animals ; Environment ; Humans ; Models, Theoretical ; Mosquito Vectors ; Rift Valley Fever/*epidemiology/transmission/virology ; Seasons ; Temperature ; }, abstract = {Vector-borne diseases (VBDs) of humans and domestic animals are a significant component of the global burden of disease and a key driver of poverty. The transmission cycles of VBDs are often strongly mediated by the ecological requirements of the vectors, resulting in complex transmission dynamics, including intermittent epidemics and an unclear link between environmental conditions and disease persistence. An important broader concern is the extent to which theoretical models are reliable at forecasting VBDs; infection dynamics can be complex, and the resulting systems are highly unstable. Here, we examine these problems in detail using a case study of Rift Valley fever (RVF), a high-burden disease endemic to Africa. We develop an ecoepidemiological, compartmental, mathematical model coupled to the dynamics of ambient temperature and water availability and apply it to a realistic setting using empirical environmental data from Kenya. Importantly, we identify the range of seasonally varying ambient temperatures and water-body availability that leads to either the extinction of mosquito populations and/or RVF (nonpersistent regimens) or the establishment of long-term mosquito populations and consequently, the endemicity of the RVF infection (persistent regimens). Instabilities arise when the range of the environmental variables overlaps with the threshold of persistence. The model captures the intermittent nature of RVF occurrence, which is explained as low-level circulation under the threshold of detection, with intermittent emergence sometimes after long periods. Using the approach developed here opens up the ability to improve predictions of the emergence and behaviors of epidemics of many other important VBDs.}, } @article {pmid30021854, year = {2018}, author = {Kerosuo, L and Neppala, P and Hsin, J and Mohlin, S and Vieceli, FM and Török, Z and Laine, A and Westermarck, J and Bronner, ME}, title = {Enhanced expression of MycN/CIP2A drives neural crest toward a neural stem cell-like fate: Implications for priming of neuroblastoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7351-E7360}, pmid = {30021854}, issn = {1091-6490}, support = {P01 HD037105/HD/NICHD NIH HHS/United States ; R01 DE024157/DE/NIDCR NIH HHS/United States ; }, mesh = {Autoantigens/analysis/*physiology ; Cell Movement ; Humans ; Membrane Proteins/analysis/*physiology ; N-Myc Proto-Oncogene Protein/analysis/*physiology ; Neural Crest/*cytology ; Neural Stem Cells/*physiology ; Neuroblastoma/*etiology/pathology ; SOXB1 Transcription Factors/analysis ; }, abstract = {Neuroblastoma is a neural crest-derived childhood tumor of the peripheral nervous system in which MycN amplification is a hallmark of poor prognosis. Here we show that MycN is expressed together with phosphorylation-stabilizing factor CIP2A in regions of the neural plate destined to form the CNS, but MycN is excluded from the neighboring neural crest stem cell domain. Interestingly, ectopic expression of MycN or CIP2A in the neural crest domain biases cells toward CNS-like neural stem cells that express Sox2. Consistent with this, some forms of neuroblastoma have been shown to share transcriptional resemblance with CNS neural stem cells. As high MycN/CIP2A levels correlate with poor prognosis, we posit that a MycN/CIP2A-mediated cell-fate bias may reflect a possible mechanism underlying early priming of some aggressive forms of neuroblastoma. In contrast to MycN, its paralogue cMyc is normally expressed in the neural crest stem cell domain and typically is associated with better overall survival in clinical neuroblastoma, perhaps reflecting a more "normal" neural crest-like state. These data suggest that priming for some forms of aggressive neuroblastoma may occur before neural crest emigration from the CNS and well before sympathoadrenal specification.}, } @article {pmid30021853, year = {2018}, author = {Redd, NT}, title = {Inner Workings: After years of listening with detectors buried in Antarctic ice, IceCube researchers trace neutrino source.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8463-8465}, pmid = {30021853}, issn = {1091-6490}, } @article {pmid30021852, year = {2018}, author = {Gee, MH and Sibener, LV and Birnbaum, ME and Jude, KM and Yang, X and Fernandes, RA and Mendoza, JL and Glassman, CR and Garcia, KC}, title = {Stress-testing the relationship between T cell receptor/peptide-MHC affinity and cross-reactivity using peptide velcro.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7369-E7378}, pmid = {30021852}, issn = {1091-6490}, support = {K01 CA175127/CA/NCI NIH HHS/United States ; R01 AI103867/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; F31 CA216926/CA/NCI NIH HHS/United States ; P01 AI045757/AI/NIAID NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cross Reactions ; Humans ; *Major Histocompatibility Complex ; Oligopeptides/*metabolism ; Peptide Library ; Protein Engineering ; Receptors, Antigen, T-Cell/*metabolism ; }, abstract = {T cell receptors (TCRs) bind to peptide-major histocompatibility complex (pMHC) with low affinity (Kd ∼ μM), which is generally assumed to facilitate cross-reactive TCR "scanning" of ligands. To understand the relationship between TCR/pMHC affinity and cross-reactivity, we sought to engineer an additional weak interaction, termed "velcro," between the TCR and pMHC to probe the specificities of TCRs at relatively low and high affinities. This additional interaction was generated through an eight-amino acid peptide library covalently linked to the N terminus of the MHC-bound peptide. Velcro was selected through an affinity-based isolation and was subsequently shown to enhance the cognate TCR/pMHC affinity in a peptide-dependent manner by ∼10-fold. This was sufficient to convert a nonstimulatory ultra-low-affinity ligand into a stimulatory ligand. An X-ray crystallographic structure revealed how velcro interacts with the TCR. To probe TCR cross-reactivity, we screened TCRs against yeast-displayed pMHC libraries with and without velcro, and found that the peptide cross-reactivity profiles of low-affinity (Kd > 100 μM) and high-affinity (Kd ∼ μM) TCR/pMHC interactions are remarkably similar. The conservation of recognition of the TCR for pMHC across affinities reveals the nature of low-affinity ligands for which there are important biological functions and has implications for understanding the specificities of affinity-matured TCRs.}, } @article {pmid30021851, year = {2018}, author = {Zaslavsky, N and Kemp, C and Regier, T and Tishby, N}, title = {Efficient compression in color naming and its evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7937-7942}, pmid = {30021851}, issn = {1091-6490}, abstract = {We derive a principled information-theoretic account of cross-language semantic variation. Specifically, we argue that languages efficiently compress ideas into words by optimizing the information bottleneck (IB) trade-off between the complexity and accuracy of the lexicon. We test this proposal in the domain of color naming and show that (i) color-naming systems across languages achieve near-optimal compression; (ii) small changes in a single trade-off parameter account to a large extent for observed cross-language variation; (iii) efficient IB color-naming systems exhibit soft rather than hard category boundaries and often leave large regions of color space inconsistently named, both of which phenomena are found empirically; and (iv) these IB systems evolve through a sequence of structural phase transitions, in a single process that captures key ideas associated with different accounts of color category evolution. These results suggest that a drive for information-theoretic efficiency may shape color-naming systems across languages. This principle is not specific to color, and so it may also apply to cross-language variation in other semantic domains.}, } @article {pmid30021850, year = {2018}, author = {Toska, J and Ho, BT and Mekalanos, JJ}, title = {Exopolysaccharide protects Vibrio cholerae from exogenous attacks by the type 6 secretion system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7997-8002}, pmid = {30021850}, issn = {1091-6490}, mesh = {Polysaccharides, Bacterial/genetics/*metabolism ; Type VI Secretion Systems/genetics/*metabolism ; Vibrio cholerae/genetics/*metabolism ; }, abstract = {The type 6 secretion system (T6SS) is a nanomachine used by many Gram-negative bacteria, including Vibrio cholerae, to deliver toxic effector proteins into adjacent eukaryotic and bacterial cells. Because the activity of the T6SS is dependent on direct contact between cells, its activity is limited to bacteria growing on solid surfaces or in biofilms. V. cholerae can produce an exopolysaccharide (EPS) matrix that plays a role in adhesion and biofilm formation. In this work, we investigated the effect of EPS production on T6SS activity between cells. We found that EPS produced by V. cholerae cells functions as a unidirectional protective armor that blocks exogenous T6SS attacks without interfering with its own T6SS functionality. This EPS armor is effective against both same-species and heterologous attackers. Mutations modulating the level of EPS biosynthesis gene expression result in corresponding modulation in V. cholerae resistance to exogenous T6SS attack. These results provide insight into the potential role of extracellular biopolymers, including polysaccharides, capsules, and S-layers in protecting bacterial cells from attacks involving cell-associated macromolecular protein machines that cannot readily diffuse through these mechanical defenses.}, } @article {pmid30021849, year = {2018}, author = {García-Carreras, B and Sal, S and Padfield, D and Kontopoulos, DG and Bestion, E and Schaum, CE and Yvon-Durocher, G and Pawar, S}, title = {Role of carbon allocation efficiency in the temperature dependence of autotroph growth rates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7361-E7368}, pmid = {30021849}, issn = {1091-6490}, mesh = {*Autotrophic Processes ; Carbon/*metabolism ; Ecosystem ; Models, Theoretical ; Photosynthesis ; Temperature ; }, abstract = {Relating the temperature dependence of photosynthetic biomass production to underlying metabolic rates in autotrophs is crucial for predicting the effects of climatic temperature fluctuations on the carbon balance of ecosystems. We present a mathematical model that links thermal performance curves (TPCs) of photosynthesis, respiration, and carbon allocation efficiency to the exponential growth rate of a population of photosynthetic autotroph cells. Using experiments with the green alga, Chlorella vulgaris, we apply the model to show that the temperature dependence of carbon allocation efficiency is key to understanding responses of growth rates to warming at both ecological and longer-term evolutionary timescales. Finally, we assemble a dataset of multiple terrestrial and aquatic autotroph species to show that the effects of temperature-dependent carbon allocation efficiency on potential growth rate TPCs are expected to be consistent across taxa. In particular, both the thermal sensitivity and the optimal temperature of growth rates are expected to change significantly due to temperature dependence of carbon allocation efficiency alone. Our study provides a foundation for understanding how the temperature dependence of carbon allocation determines how population growth rates respond to temperature.}, } @article {pmid30021638, year = {2018}, author = {Mushanyu, J}, title = {Role of imitation and limited rehabilitation capacity on the spread of drug abuse.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {493}, pmid = {30021638}, issn = {1756-0500}, mesh = {Humans ; Models, Theoretical ; Substance-Related Disorders/epidemiology/*rehabilitation ; }, abstract = {OBJECTIVES: We formulate a mathematical model for the spread of drug abuse using non linear ordinary differential equations. The model seeks to investigate both peer influence and limited rehabilitation effects on the dynamics of drug abuse. Peer-influence is modelled through the mechanism of imitation and limited rehabilitation is described using a special treatment function. Center manifold theory is used to show that the model exhibits the phenomenon of backward bifurcation. Matlab has been used to carry out numerical simulations to support theoretical findings.

RESULTS: The model analysis shows that the model has multiple equilibria. It has been shown that the classical [Formula: see text]-threshold is not the key to control drug abuse within a population. In fact drug abuse problems may persist in the population even with subthreshold values of [Formula: see text]. This was shown to result, in particular when, [Formula: see text], [Formula: see text] and [Formula: see text] are high enough such that [Formula: see text], [Formula: see text] and [Formula: see text]. The results suggest the need for comprehensive and accessible substance abuse treatment services to curtail drug abuse.}, } @article {pmid30021631, year = {2018}, author = {Goelema, MS and de Bruijn, R and Overeem, S and Møst, E and Haakma, R and Markopoulos, P}, title = {Conceptions of sleep experience: a layman perspective.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {494}, pmid = {30021631}, issn = {1756-0500}, mesh = {Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Polysomnography ; *Sleep ; *Sleep Wake Disorders ; Surveys and Questionnaires ; Universities ; }, abstract = {OBJECTIVE: To date, there is little information on how lay people understand and discuss sleep in the context of daily life. Efforts to conceptualize sleep quality have been largely driven by clinical considerations of sleep disorders. As such, they are not necessarily of how normal sleepers without clinical expertise conceptualize sleep quality. A phenomenological approach was taken to understand the essence of the sleep experience and the concepts held by lay people without sleep disorders. A sentence completion questionnaire was developed and administered to a quota sample of 64 respondents who were selected aiming for sufficient representation of different gender, ages, and education levels.

RESULTS: Significant sentences and meaningful units were derived inductively, resulting in a classification of nine categories. The major facets of sleep experience of lay people were 'daytime functioning', 'interruptions during the night' and 'before bed state'. This implies that the experienced sleep quality is not only depending on the progress of the night. These results can guide future research to provide suitable psychometric measures for normal sleepers, as well as the design of sleep data visualization applications in the context of health self-monitoring.}, } @article {pmid30021627, year = {2018}, author = {Alelign, A and Petros, B}, title = {Knowledge, attitudes and practices of malaria transmission and preventive measures in Woreta town, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {491}, pmid = {30021627}, issn = {1756-0500}, support = {GSR/2748/05//Addis Ababa University/ ; }, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Ethiopia ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; *Insecticide-Treated Bednets ; Malaria/prevention & control/*transmission ; Male ; Middle Aged ; *Mosquito Control ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Despite a high public health burden of malaria in endemic regions of Ethiopia, there are limitations on the availability of data concerning public awareness about the disease and its preventive measures. The present study aimed in producing base line data on the community knowledge, attitudes and practices towards malaria transmission and its preventive measures in Woreta town, northwest Ethiopia. A community based two-stage random cluster study was conducted from May to July 2013. Household heads were interviewed to assess their awareness about malaria and its control measures.

RESULTS: About 78.5% (113/144) of the respondents rated bite of infected mosquito as a way of malaria transmission. The majority of participants, 126 (87.5%) stated one or more symptoms of malaria. About 95.8% (138/144) of the respondents indicated that malaria is preventable and curable disease. Only about 25% (36/144) of the study participants practiced frequent and proper use of insecticide treated bed nets (ITNs). Draining logged water was a highly rated, 83 (57.6%), practice of environmental management of malaria.}, } @article {pmid30021621, year = {2018}, author = {Almeida-Souza, F and de Oliveira, AER and Abreu-Silva, AL and da Silva Calabrese, K}, title = {In vitro activity of Morinda citrifolia Linn. fruit juice against the axenic amastigote form of Leishmania amazonensis and its hydrogen peroxide induction capacity in BALB/c peritoneal macrophages.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {492}, pmid = {30021621}, issn = {1756-0500}, support = {E-26/111.252/2014//Fundação Carlos Chagas Filho de Amparo à Pesquisa do Estado do Rio de Janeiro/ ; APP-00844/09//Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão/ ; Pronex-241709/2014//Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão/ ; DCR FAPEMA 03438-16//Fundação de Amparo à Pesquisa e ao Desenvolvimento Científico e Tecnológico do Maranhão/ ; 407831/2012.6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309885/2017-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; DCR CNPq 312765_2016-9//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Animals ; Female ; Fruit ; *Fruit and Vegetable Juices ; Hydrogen Peroxide ; Leishmania/*drug effects ; *Macrophages, Peritoneal ; Mice ; Mice, Inbred BALB C ; Morinda/*chemistry ; }, abstract = {OBJECTIVE: The current treatment of leishmaniasis induces strong side effects and increasing numbers of cases of resistance to reference drugs have been reported. The discovery of the therapeutic properties of active substances in plant extracts represents an interesting field of research into a more efficient treatment against leishmaniasis. Morinda citrifolia, commonly known as noni, has demonstrated promising results as antileishmanial and immunomodulator. Thus, the aim of this work was to evaluate activity against axenic amastigote and hydrogen peroxide induction capacity by M. citrifolia fruit juice.

RESULTS: Phytochemical screening identified anthraquinones, flavonoids, alkaloids, terpenoids, steroids, saponins, coumarins, phenolic compounds, tannins, anthocyanidins and chalcones. Noni juice exhibited dose-dependent activity and an IC50 of 240.1 µg/mL for axenic amastigotes. An absence of endotoxins was observed at the concentrations analyzed, while no cytotoxic effects were identified. Noni juice induced hydrogen peroxide production in BALB/c peritoneal macrophages but not in macrophages infected with Leishmania amazonensis. M. citrifolia fruit juice exhibited antileishmanial activity against L. amazonensis axenic amastigotes and activated macrophages by hydrogen peroxide induction, asserting its potential for further research into new forms of leishmaniasis treatment.}, } @article {pmid30021534, year = {2018}, author = {Quinn, TP and Crowley, TM and Richardson, MF}, title = {Benchmarking differential expression analysis tools for RNA-Seq: normalization-based vs. log-ratio transformation-based methods.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {274}, pmid = {30021534}, issn = {1471-2105}, abstract = {BACKGROUND: Count data generated by next-generation sequencing assays do not measure absolute transcript abundances. Instead, the data are constrained to an arbitrary "library size" by the sequencing depth of the assay, and typically must be normalized prior to statistical analysis. The constrained nature of these data means one could alternatively use a log-ratio transformation in lieu of normalization, as often done when testing for differential abundance (DA) of operational taxonomic units (OTUs) in 16S rRNA data. Therefore, we benchmark how well the ALDEx2 package, a transformation-based DA tool, detects differential expression in high-throughput RNA-sequencing data (RNA-Seq), compared to conventional RNA-Seq methods such as edgeR and DESeq2.

RESULTS: To evaluate the performance of log-ratio transformation-based tools, we apply the ALDEx2 package to two simulated, and two real, RNA-Seq data sets. One of the latter was previously used to benchmark dozens of conventional RNA-Seq differential expression methods, enabling us to directly compare transformation-based approaches. We show that ALDEx2, widely used in meta-genomics research, identifies differentially expressed genes (and transcripts) from RNA-Seq data with high precision and, given sufficient sample sizes, high recall too (regardless of the alignment and quantification procedure used). Although we show that the choice in log-ratio transformation can affect performance, ALDEx2 has high precision (i.e., few false positives) across all transformations. Finally, we present a novel, iterative log-ratio transformation (now implemented in ALDEx2) that further improves performance in simulations.

CONCLUSIONS: Our results suggest that log-ratio transformation-based methods can work to measure differential expression from RNA-Seq data, provided that certain assumptions are met. Moreover, these methods have very high precision (i.e., few false positives) in simulations and perform well on real data too. With previously demonstrated applicability to 16S rRNA data, ALDEx2 can thus serve as a single tool for data from multiple sequencing modalities.}, } @article {pmid30021531, year = {2018}, author = {Orr, RJS and Zhao, S and Klaveness, D and Yabuki, A and Ikeda, K and Watanabe, MM and Shalchian-Tabrizi, K}, title = {Enigmatic Diphyllatea eukaryotes: culturing and targeted PacBio RS amplicon sequencing reveals a higher order taxonomic diversity and global distribution.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {115}, pmid = {30021531}, issn = {1471-2148}, support = {230868//Norges Forskningsråd/International ; }, mesh = {*Biodiversity ; DNA Primers/metabolism ; Ecosystem ; Eukaryota/*classification/cytology/*genetics ; Fresh Water ; Phylogeny ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The class Diphyllatea belongs to a group of enigmatic unicellular eukaryotes that play a key role in reconstructing the morphological innovation and diversification of early eukaryotic evolution. Despite its evolutionary significance, very little is known about the phylogeny and species diversity of Diphyllatea. Only three species have described morphology, being taxonomically divided by flagella number, two or four, and cell size. Currently, one 18S rRNA Diphyllatea sequence is available, with environmental sequencing surveys reporting only a single partial sequence from a Diphyllatea-like organism. Accordingly, geographical distribution of Diphyllatea based on molecular data is limited, despite morphological data suggesting the class has a global distribution. We here present a first attempt to understand species distribution, diversity and higher order structure of Diphyllatea.

RESULTS: We cultured 11 new strains, characterised these morphologically and amplified their rRNA for a combined 18S-28S rRNA phylogeny. We sampled environmental DNA from multiple sites and designed new Diphyllatea-specific PCR primers for long-read PacBio RSII technology. Near full-length 18S rRNA sequences from environmental DNA, in addition to supplementary Diphyllatea sequence data mined from public databases, resolved the phylogeny into three deeply branching and distinct clades (Diphy I - III). Of these, the Diphy III clade is entirely novel, and in congruence with Diphy II, composed of species morphologically consistent with the earlier described Collodictyon triciliatum. The phylogenetic split between the Diphy I and Diphy II + III clades corresponds with a morphological division of Diphyllatea into bi- and quadriflagellate cell forms.

CONCLUSIONS: This altered flagella composition must have occurred early in the diversification of Diphyllatea and may represent one of the earliest known morphological transitions among eukaryotes. Further, the substantial increase in molecular data presented here confirms Diphyllatea has a global distribution, seemingly restricted to freshwater habitats. Altogether, the results reveal the advantage of combining a group-specific PCR approach and long-read high-throughput amplicon sequencing in surveying enigmatic eukaryote lineages. Lastly, our study shows the capacity of PacBio RS when targeting a protist class for increasing phylogenetic resolution.}, } @article {pmid30021530, year = {2018}, author = {Yamada, KD and Kinoshita, K}, title = {De novo profile generation based on sequence context specificity with the long short-term memory network.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {272}, pmid = {30021530}, issn = {1471-2105}, support = {18K18143//Japan Society for the Promotion of Science/ ; }, abstract = {BACKGROUND: Long short-term memory (LSTM) is one of the most attractive deep learning methods to learn time series or contexts of input data. Increasing studies, including biological sequence analyses in bioinformatics, utilize this architecture. Amino acid sequence profiles are widely used for bioinformatics studies, such as sequence similarity searches, multiple alignments, and evolutionary analyses. Currently, many biological sequences are becoming available, and the rapidly increasing amount of sequence data emphasizes the importance of scalable generators of amino acid sequence profiles.

RESULTS: We employed the LSTM network and developed a novel profile generator to construct profiles without any assumptions, except for input sequence context. Our method could generate better profiles than existing de novo profile generators, including CSBuild and RPS-BLAST, on the basis of profile-sequence similarity search performance with linear calculation costs against input sequence size. In addition, we analyzed the effects of the memory power of LSTM and found that LSTM had high potential power to detect long-range interactions between amino acids, as in the case of beta-strand formation, which has been a difficult problem in protein bioinformatics using sequence information.

CONCLUSION: We demonstrated the importance of sequence context and the feasibility of LSTM on biological sequence analyses. Our results demonstrated the effectiveness of memories in LSTM and showed that our de novo profile generator, SPBuild, achieved higher performance than that of existing methods for profile prediction of beta-strands, where long-range interactions of amino acids are important and are known to be difficult for the existing window-based prediction methods. Our findings will be useful for the development of other prediction methods related to biological sequences by machine learning methods.}, } @article {pmid30021523, year = {2018}, author = {Morris, MRJ and Bowles, E and Allen, BE and Jamniczky, HA and Rogers, SM}, title = {Contemporary ancestor? Adaptive divergence from standing genetic variation in Pacific marine threespine stickleback.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {113}, pmid = {30021523}, issn = {1471-2148}, support = {Discovery Grant RT735287//Natural Sciences and Engineering Research Council of Canada/International ; Vanier Scholarship//Natural Sciences and Engineering Research Council of Canada/International ; 418249-2012//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {Adaptation, Physiological/*genetics ; Alaska ; Animals ; Aquatic Organisms/*genetics ; Base Sequence ; California ; Female ; Fresh Water ; Gene Frequency/genetics ; *Genetic Variation ; Genetics, Population ; Genotype ; Geography ; Male ; Pacific Ocean ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Selection, Genetic ; Smegmamorpha/*genetics ; Washington ; }, abstract = {BACKGROUND: Populations that have repeatedly colonized novel environments are useful for studying the role of ecology in adaptive divergence - particularly if some individuals persist in the ancestral habitat. Such "contemporary ancestors" can be used to demonstrate the effects of selection by comparing phenotypic and genetic divergence between the derived population and their extant ancestors. However, evolution and demography in these "contemporary ancestors" can complicate inferences about the source (standing genetic variation, de novo mutation) and pace of adaptive divergence. Marine threespine stickleback (Gasterosteus aculeatus) have colonized freshwater environments along the Pacific coast of North America, but have also persisted in the marine environment. To what extent are marine stickleback good proxies of the ancestral condition?

RESULTS: We sequenced > 5800 variant loci in over 250 marine stickleback from eight locations extending from Alaska to California, and phenotyped them for platedness and body shape. Pairwise FST varied from 0.02 to 0.18. Stickleback were divided into five genetic clusters, with a single cluster comprising stickleback from Washington to Alaska. Plate number, Eda, body shape, and candidate loci showed evidence of being under selection in the marine environment. Comparisons to a freshwater population demonstrated that candidate loci for freshwater adaptation varied depending on the choice of marine populations.

CONCLUSIONS: Marine stickleback are structured into phenotypically and genetically distinct populations that have been evolving as freshwater stickleback evolved. This variation complicates their usefulness as proxies of the ancestors of freshwater populations. Lessons from stickleback may be applied to other "contemporary ancestor"-derived population studies.}, } @article {pmid30021522, year = {2018}, author = {Foster, KL and Piller, KR}, title = {Disentangling the drivers of diversification in an imperiled group of freshwater fishes (Cyprinodontiformes: Goodeidae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {116}, pmid = {30021522}, issn = {1471-2148}, support = {1354930//Directorate for Biological Sciences/International ; }, mesh = {Animals ; *Biodiversity ; Calibration ; Cyprinodontiformes/anatomy & histology/*classification ; *Endangered Species ; *Fresh Water ; Geography ; Mexico ; Phylogeny ; Species Specificity ; Time Factors ; }, abstract = {BACKGROUND: One of the most perplexing questions in evolutionary biology is why some lineages diversify into many species, and others do not. In many cases, ecological opportunity has played an important role, leading to diversification along trophic or habitat-based axes. The Goodeidae (Teleostomi: Cyprinodontiformes) are a family of freshwater fishes with two subfamilies: Goodeinae (42 species, viviparous, heterogeneous habitats, Mesa Central of Mexico) and Empetrichthyinae (4 species, oviparous, homogeneous habitats, Great Basin of the United States). These discrepant sets of characteristics and their sister-group relationship make the goodeids amenable to a comparative study of diversification. We gathered lateral body images from more than 1600 specimens of all extant species in the family. Geometric morphometric, and phylogenetic comparative analyses were used to address whether higher species diversity correlates with higher rates of morphological shape evolution and whether there are differences in functional/habitat modules between the two subfamilies.

RESULTS: This study recovered a higher rate of overall body shape evolution in the Goodeinae that is nearly double in magnitude compared to the Empetrichthyinae. A modularity test indicated that the Goodeinae displayed elevated rates of morphological evolution in comparison to the Empetrichthyinae when only trunk (locomotor) regions were compared between subfamilies. No significant differences in evolutionary shape rates were recovered when the trophic (head) regions were compared between subfamilies.

DISCUSSION: These results support the hypothesis that Mexican goodeids radiated via an ecological opportunity scenario into a wide-array of novel habitats in the island-like Mesa Central as evidenced by their high rate of shape evolution, relative to the Empetrichthyinae. This study quantitatively unraveled the drivers of evolution and eliminated trophic specialization as a driving force within the Goodeidae.

CONCLUSIONS: A combination of phylogenetic and morphometric data, and phylogenetic comparative analyses were used to examine body shape rate evolution within the Goodeidae. Results support the hypothesis that species in the subfamily Goodeinae on the central Mexican plateau had a higher rate of body shape evolution relative to its sister subfamily Empetrichthyinae in the Great Basin suggesting that the Goodeinae diversified via an ecological opportunity scenario along habitat, rather than trophic axes.}, } @article {pmid30021519, year = {2018}, author = {Zhang, C and Song, L and Choudhary, MK and Zhou, B and Sun, G and Broderick, K and Giesler, L and Zeng, L}, title = {Genome-wide analysis of genes encoding core components of the ubiquitin system in soybean (Glycine max) reveals a potential role for ubiquitination in host immunity against soybean cyst nematode.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {149}, pmid = {30021519}, issn = {1471-2229}, support = {1719//Nebraska Soybean Board/ ; }, abstract = {BACKGROUND: Ubiquitination is a major post-translational protein modification that regulates essentially all cellular and physiological pathways in eukaryotes. The ubiquitination process typically involves three distinct classes of enzymes, ubiquitin-activating enzyme (E1), ubiquitin-conjugating enzyme (E2) and ubiquitin ligase (E3). To date, a comprehensive identification and analysis of core components comprising of the whole soybean (Glycine max) ubiquitin system (UBS) has not been reported.

RESULTS: We performed a systematic, genome-wide analysis of genes that encode core members of the soybean UBS in this study. A total of 1431 genes were identified with high confidence to encode putative soybean UBS components, including 4 genes encoding E1s, 71 genes that encode the E2s, and 1356 genes encoding the E3-related components. Among the E3-encoding genes, 760 encode RING-type E3s, 124 encode U-box domain-containing E3s, and 472 encode F-box proteins. To find out whether the identified soybean UBS genes encode active enzymes, a set of genes were randomly selected and the enzymatic activities of their recombinant proteins were tested. Thioester assays indicated proteins encoded by the soybean E1 gene GmUBA1 and the majority of selected E2 genes are active E1 or E2 enzymes, respectively. Meanwhile, most of the purified RING and U-box domain-containing proteins displayed E3 activity in the in vitro ubiquitination assay. In addition, 1034 of the identified soybean UBS genes were found to express in at least one of 14 soybean tissues examined and the transcript level of 338 soybean USB genes were significantly changed after abiotic or biotic (Fusarium oxysporum and Rhizobium strains) stress treatment. Finally, the expression level of a large number of the identified soybean UBS-related genes was found significantly altered after soybean cyst nematode (SCN) treatment, suggesting the soybean UBS potentially plays an important role in soybean immunity against SCN.

CONCLUSIONS: Our findings indicate the presence of a large and diverse number of core UBS proteins in the soybean genome, which suggests that target-specific modification by ubiquitin is a complex and important part of cellular and physiological regulation in soybean. We also revealed certain members of the soybean UBS may be involved in immunity against soybean cyst nematode (SCN). This study sets up an essential foundation for further functional characterization of the soybean UBS in various physiological processes, such as host immunity against SCN.}, } @article {pmid30021517, year = {2018}, author = {Birkeland, Å and ChyŻyńska, K and Valen, E}, title = {Shoelaces: an interactive tool for ribosome profiling processing and visualization.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {543}, pmid = {30021517}, issn = {1471-2164}, support = {#250049//Bergens Forskningsstiftelse/ ; 250049//Norges Forskningsråd (NO)/ ; }, mesh = {Computer Graphics ; Genomics/methods ; Humans ; *Protein Biosynthesis ; Ribosomes/chemistry/*metabolism ; *Software ; Workflow ; }, abstract = {BACKGROUND: The emergence of ribosome profiling to map actively translating ribosomes has laid the foundation for a diverse range of studies on translational regulation. The data obtained with different variations of this assay is typically manually processed, which has created a need for tools that would streamline and standardize processing steps.

RESULTS: We present Shoelaces, a toolkit for ribosome profiling experiments automating read selection and filtering to obtain genuine translating footprints. Based on periodicity, favoring enrichment over the coding regions, it determines the read lengths corresponding to bona fide ribosome protected fragments. The specific codon under translation (P-site) is determined by automatic offset calculations resulting in sub-codon resolution. Shoelaces provides both a user-friendly graphical interface for interactive visualisation in a genome browser-like fashion and a command line interface for integration into automated pipelines. We process 79 libraries and show that studies typically discard excessive amounts of quality data in their manual analysis pipelines.

CONCLUSIONS: Shoelaces streamlines ribosome profiling analysis offering automation of the processing, a range of interactive visualization features and export of the data into standard formats. Shoelaces stores all processing steps performed in an XML file that can be used by other groups to exactly reproduce the processing of a given study. We therefore anticipate that Shoelaces can aid researchers by automating what is typically performed manually and contribute to the overall reproducibility of studies. The tool is freely distributed as a Python package, with additional instructions, tutorial and demo datasets available at https://bitbucket.org/valenlab/shoelaces .}, } @article {pmid30021516, year = {2018}, author = {Schuster, A and Vargas, S and Knapp, IS and Pomponi, SA and Toonen, RJ and Erpenbeck, D and Wörheide, G}, title = {Divergence times in demosponges (Porifera): first insights from new mitogenomes and the inclusion of fossils in a birth-death clock model.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {114}, pmid = {30021516}, issn = {1471-2148}, support = {Wo896/15-1//Deutsche Forschungsgemeinschaft/International ; ER 611/3-1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Animals ; Aquatic Organisms/genetics ; Bayes Theorem ; Calibration ; Evolution, Molecular ; *Fossils ; Fresh Water ; *Genome, Mitochondrial ; *Models, Biological ; Phylogeny ; Porifera/*genetics ; Time Factors ; }, abstract = {BACKGROUND: Approximately 80% of all described extant sponge species belong to the class Demospongiae. Yet, despite their diversity and importance, accurate divergence times are still unknown for most demosponge clades. The estimation of demosponge divergence time is key to answering fundamental questions on the origin of Demospongiae, their diversification and historical biogeography. Molecular sequence data alone is not informative on an absolute time scale, and therefore needs to be "calibrated" with additional data such as fossils. Here, we calibrate the molecular data with the fossilized birth-death model, which compared to strict node dating, allows for the inclusion of young and old fossils in the analysis of divergence time. We use desma-bearing sponges, a diverse group of demosponges that form rigid skeletons and have a rich and continuous fossil record dating back to the Cambrian (~500 Ma), to date the demosponge radiation and constrain the timing of key evolutionary events, like the transition from marine to freshwater habitats. To infer a dated phylogeny of Demospongiae we assembled the mitochondrial genomes of six desma-bearing demosponges from reduced-representation genomic libraries. The total dataset included 33 complete demosponge mitochondrial genomes and 30 fossils.

RESULTS: Our study supports a Neoproterozoic origin of Demospongiae. Novel age estimates for the split of freshwater and marine sponges dating back to the Carboniferous and the previously assumed recent (~18 Ma) diversification of freshwater sponges is supported. Moreover, we provide detailed age estimates for a possible diversification of Tetractinellidae (~315 Ma), the Astrophorina (~240 Ma), the Spirophorina (~120 Ma) and the family Corallistidae (~188 Ma) all of which are considered as key groups for dating the Demospongiae due to their extraordinary rich and continuous fossil history.

CONCLUSION: This study provides novel insights into the evolution of Demospongiae. Observed discrepancies of our dated phylogeny with their putative first fossil appearance dates are discussed for selected sponge groups. For instance, a Carboniferous origin of the order Tetractinellida seems to be too late, compared to their first appearance in the fossil record in the Middle Cambrian. This would imply that Paleozoic spicule forms are not homologous to post-Paleozoic forms.}, } @article {pmid30021513, year = {2018}, author = {Kuśmirek, W and Nowak, R}, title = {De novo assembly of bacterial genomes with repetitive DNA regions by dnaasm application.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {273}, pmid = {30021513}, issn = {1471-2105}, support = {2014/13/B/NZ6/00881//Polish National Science Centre/ ; }, abstract = {BACKGROUND: Many organisms, in particular bacteria, contain repetitive DNA fragments called tandem repeats. These structures are restored by DNA assemblers by mapping paired-end tags to unitigs, estimating the distance between them and filling the gap with the specified DNA motif, which could be repeated many times. However, some of the tandem repeats are longer than the distance between the paired-end tags.

RESULTS: We present a new algorithm for de novo DNA assembly, which uses the relative frequency of reads to properly restore tandem repeats. The main advantage of the presented algorithm is that long tandem repeats, which are much longer than maximum reads length and the insert size of paired-end tags can be properly restored. Moreover, repetitive DNA regions covered only by single-read sequencing data could also be restored. Other existing de novo DNA assemblers fail in such cases. The presented application is composed of several steps, including: (i) building the de Bruijn graph, (ii) correcting the de Bruijn graph, (iii) normalizing edge weights, and (iv) generating the output set of DNA sequences. We tested our approach on real data sets of bacterial organisms.

CONCLUSIONS: The software library, console application and web application were developed. Web application was developed in client-server architecture, where web-browser is used to communicate with end-user and algorithms are implemented in C++ and Python. The presented approach enables proper reconstruction of tandem repeats, which are longer than the insert size of paired-end tags. The application is freely available to all users under GNU Library or Lesser General Public License version 3.0 (LGPLv3).}, } @article {pmid30020850, year = {2019}, author = {Johnston, DW}, title = {Unoccupied Aircraft Systems in Marine Science and Conservation.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {439-463}, doi = {10.1146/annurev-marine-010318-095323}, pmid = {30020850}, issn = {1941-0611}, abstract = {The use of unoccupied aircraft systems (UASs, also known as drones) in science is growing rapidly. Recent advances in microelectronics and battery technology have resulted in the rapid development of low-cost UASs that are transforming many industries. Drones are poised to revolutionize marine science and conservation, as they provide essentially on-demand remote sensing capabilities at low cost and with reduced human risk. A variety of multirotor, fixed-wing, and transitional UAS platforms are capable of carrying various optical and physical sampling payloads and are being employed in almost every subdiscipline of marine science and conservation. This article provides an overview of the UAS platforms and sensors used in marine science and conservation missions along with example physical, biological, and natural resource management applications and typical analytical workflows. It concludes with details on potential effects of UASs on marine wildlife and a look to the future of UASs in marine science and conservation.}, } @article {pmid30020488, year = {2018}, author = {Tangwancharoen, S and Moy, GW and Burton, RS}, title = {Multiple modes of adaptation: regulatory and structural evolution in a small heat shock protein gene.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy138}, pmid = {30020488}, issn = {1537-1719}, abstract = {Thermal tolerance is a key determinant of species distribution. Despite much study, the genetic basis of adaptive evolution of thermal tolerance, including the relative contributions of transcriptional regulation versus protein evolution, remains unclear. Populations of the intertidal copepod Tigriopus californicus are adapted to local thermal regimes across their broad geographic range. Upon thermal stress, adults from a heat tolerant southern population (San Diego) upregulate several heat shock proteins (HSPs) to higher levels than those from a less tolerant northern population (Santa Cruz). Suppression of a specific HSP, HSPB1, significantly reduces T. californicus survival following acute heat stress. Sequencing of HSPB1 revealed population specific nucleotide substitutions in both promoter and coding regions of the gene. HSPB1 promoters from heat tolerant populations contain two canonical heat shock elements (HSEs), the binding sites for heat shock transcription factor (HSF), while less tolerant populations have mutations in these conserved motifs. Allele specific expression of HSPB1 in F1 hybrids between tolerant and less tolerant populations showed significantly biased expression favoring alleles from tolerant populations and supporting the adaptive divergence in these cis-regulatory variants. The functional impact of population-specific non-synonymous substitutions in HSPB1 coding sequences was tested by assessing the thermal stabilization properties of SD versus SC HSPB1 protein variants. Recombinant HSPB1 from the southern SD population showed greater capacity for protecting protein structure under elevated temperature. Our results indicate that both regulatory and protein coding sequence evolution within a single gene appear to contribute to thermal tolerance phenotypes and local adaptation among conspecific populations.}, } @article {pmid30019746, year = {2018}, author = {Braga, MP and Araujo, SBL and Agosta, S and Brooks, D and Hoberg, E and Nylin, S and Janz, N and Boeger, WA}, title = {Host use dynamics in a heterogeneous fitness landscape generates oscillations in host range and diversification.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1773-1783}, doi = {10.1111/evo.13557}, pmid = {30019746}, issn = {1558-5646}, support = {2015-0009//Marcus Wallenbergs Stiftelse för Internationellt Vetenskapligt Samarbete/ ; 2015-04218//Vetenskapsrådet/ ; }, abstract = {Colonization of novel hosts is thought to play an important role in parasite diversification, yet little consensus has been achieved about the macroevolutionary consequences of changes in host use. Here, we offer a mechanistic basis for the origins of parasite diversity by simulating lineages evolved in silico. We describe an individual-based model in which (i) parasites undergo sexual reproduction limited by genetic proximity, (ii) hosts are uniformly distributed along a one-dimensional resource gradient, and (iii) host use is determined by the interaction between the phenotype of the parasite and a heterogeneous fitness landscape. We found two main effects of host use on the evolution of a parasite lineage. First, the colonization of a novel host allowed parasites to explore new areas of the resource space, increasing phenotypic and genotypic variation. Second, hosts produced heterogeneity in the parasite fitness landscape, which led to reproductive isolation and therefore, speciation. As a validation of the model, we analyzed empirical data from Nymphalidae butterflies and their host plants. We then assessed the number of hosts used by parasite lineages and the diversity of resources they encompass. In both simulated and empirical systems, host diversity emerged as the main predictor of parasite species richness.}, } @article {pmid30019372, year = {2018}, author = {Wright, J and Bolstad, GH and Araya-Ajoy, YG and Dingemanse, NJ}, title = {Life-history evolution under fluctuating density-dependent selection and the adaptive alignment of pace-of-life syndromes.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12451}, pmid = {30019372}, issn = {1469-185X}, abstract = {We present a novel perspective on life-history evolution that combines recent theoretical advances in fluctuating density-dependent selection with the notion of pace-of-life syndromes (POLSs) in behavioural ecology. These ideas posit phenotypic co-variation in life-history, physiological, morphological and behavioural traits as a continuum from the highly fecund, short-lived, bold, aggressive and highly dispersive 'fast' types at one end of the POLS to the less fecund, long-lived, cautious, shy, plastic and socially responsive 'slow' types at the other. We propose that such variation in life histories and the associated individual differences in behaviour can be explained through their eco-evolutionary dynamics with population density - a single and ubiquitous selective factor that is present in all biological systems. Contrasting regimes of environmental stochasticity are expected to affect population density in time and space and create differing patterns of fluctuating density-dependent selection, which generates variation in fast versus slow life histories within and among populations. We therefore predict that a major axis of phenotypic co-variation in life-history, physiological, morphological and behavioural traits (i.e. the POLS) should align with these stochastic fluctuations in the multivariate fitness landscape created by variation in density-dependent selection. Phenotypic plasticity and/or genetic (co-)variation oriented along this major POLS axis are thus expected to facilitate rapid and adaptively integrated changes in various aspects of life histories within and among populations and/or species. The fluctuating density-dependent selection POLS framework presented here therefore provides a series of clear testable predictions, the investigation of which should further our fundamental understanding of life-history evolution and thus our ability to predict natural population dynamics.}, } @article {pmid30019131, year = {2018}, author = {De Gregorio, E and Esposito, EP and Zarrilli, R and Di Nocera, PP}, title = {Contact-Dependent Growth Inhibition Proteins in Acinetobacter baylyi ADP1.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1434-1440}, pmid = {30019131}, issn = {1432-0991}, mesh = {Acinetobacter/chemistry/genetics/growth & development/*physiology ; Bacterial Adhesion ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biofilms ; *Contact Inhibition ; Epithelial Cells/microbiology ; Humans ; Membrane Proteins/genetics/*metabolism ; Protein Domains ; }, abstract = {Bacterial contact-dependent growth inhibition (CDI) systems are two-partner secretion systems in which toxic CdiA proteins are exported on the outer membrane by cognate transporter CdiB proteins. Upon binding to specific receptors, the C-terminal toxic (CT) domain, detached from CdiA, is delivered to neighbouring cells. Contacts inhibit the growth of not-self-bacteria, lacking immunity proteins co-expressed with CdiA, but promote cooperative behaviours in "self" bacteria, favouring the formation of biofilm structures. The Acinetobacter baylyi ADP1 strain features two CdiA, which differ significantly in size and have different CT domains. Homologous proteins sharing the same CT domains have been identified in A. baumannii. The growth inhibition property of the two A. baylyi CdiA proteins was supported by competition assays between wild-type cells and mutants lacking immunity genes. However, neither protein plays a role in biofilm formation or adherence to epithelial cells, as proved by assays carried out with knockout mutants. Inhibitory and stimulatory properties may be similarly uncoupled in A. baumannii proteins.}, } @article {pmid30018448, year = {2018}, author = {}, title = {With Pruitt gone, Trump and his allies continue to threaten the EPA.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {301}, doi = {10.1038/d41586-018-05744-3}, pmid = {30018448}, issn = {1476-4687}, } @article {pmid30018447, year = {2018}, author = {Kornblihtt, A}, title = {Why I testified in the Argentina abortion debate.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {303}, doi = {10.1038/d41586-018-05746-1}, pmid = {30018447}, issn = {1476-4687}, } @article {pmid30018446, year = {2018}, author = {Witze, A}, title = {Jupiter has 10 more moons we didn't know about - and they're weird.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {312-313}, doi = {10.1038/d41586-018-05725-6}, pmid = {30018446}, issn = {1476-4687}, } @article {pmid30018445, year = {2018}, author = {Dance, A}, title = {How retirement can give your career a new lease of life.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {429-431}, doi = {10.1038/d41586-018-05715-8}, pmid = {30018445}, issn = {1476-4687}, } @article {pmid30018443, year = {2018}, author = {McCarthy, GD and Thorne, PW}, title = {Sluggish Atlantic circulation could cause global temperatures to surge.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {340-341}, doi = {10.1038/d41586-018-05712-x}, pmid = {30018443}, issn = {1476-4687}, mesh = {Atlantic Ocean ; *Global Warming ; Seawater ; *Temperature ; Water Movements ; }, } @article {pmid30018442, year = {2018}, author = {Ledford, H}, title = {Gene therapy in mouse fetuses treats deadly disease.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {313-314}, doi = {10.1038/d41586-018-05726-5}, pmid = {30018442}, issn = {1476-4687}, } @article {pmid30018440, year = {2018}, author = {Cyranoski, D}, title = {China expands surveillance of sewage to police illegal drug use.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {310-311}, doi = {10.1038/d41586-018-05728-3}, pmid = {30018440}, issn = {1476-4687}, } @article {pmid30018439, year = {2018}, author = {Zou, J and Schiebinger, L}, title = {AI can be sexist and racist - it's time to make it fair.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {324-326}, doi = {10.1038/d41586-018-05707-8}, pmid = {30018439}, issn = {1476-4687}, } @article {pmid30018436, year = {2018}, author = {Van Noorden, R}, title = {Science journals end open-access trial with Gates Foundation.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {311-312}, doi = {10.1038/d41586-018-05729-2}, pmid = {30018436}, issn = {1476-4687}, } @article {pmid30018433, year = {2018}, author = {Castelvecchi, D}, title = {Single subatomic particle illuminates mysterious origins of cosmic rays.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {309-310}, doi = {10.1038/d41586-018-05703-y}, pmid = {30018433}, issn = {1476-4687}, } @article {pmid30018367, year = {2018}, author = {Sloan, DB and Warren, JM and Williams, AM and Wu, Z and Abdel-Ghany, SE and Chicco, AJ and Havird, JC}, title = {Cytonuclear integration and co-evolution.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {635-648}, doi = {10.1038/s41576-018-0035-9}, pmid = {30018367}, issn = {1471-0064}, abstract = {The partitioning of genetic material between the nucleus and cytoplasmic (mitochondrial and plastid) genomes within eukaryotic cells necessitates coordinated integration between these genomic compartments, with important evolutionary and biomedical implications. Classic questions persist about the pervasive reduction of cytoplasmic genomes via a combination of gene loss, transfer and functional replacement - and yet why they are almost always retained in some minimal form. One striking consequence of cytonuclear integration is the existence of 'chimeric' enzyme complexes composed of subunits encoded in two different genomes. Advances in structural biology and comparative genomics are yielding important insights into the evolution of such complexes, including correlated sequence changes and recruitment of novel subunits. Thus, chimeric cytonuclear complexes provide a powerful window into the mechanisms of molecular co-evolution.}, } @article {pmid30018358, year = {2018}, author = {York, A}, title = {Delivery of the gut microbiome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {520-521}, doi = {10.1038/s41579-018-0059-3}, pmid = {30018358}, issn = {1740-1534}, } @article {pmid30018346, year = {2018}, author = {Rintoul, SR and Chown, SL and DeConto, RM and England, MH and Fricker, HA and Masson-Delmotte, V and Naish, TR and Siegert, MJ and Xavier, JC}, title = {Author Correction: Choosing the future of Antarctica.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {E5}, doi = {10.1038/s41586-018-0369-7}, pmid = {30018346}, issn = {1476-4687}, abstract = {On page 234 of this Perspective, '50% decrease' has been corrected online to '50% increase' in the sentence "The pH of surface waters south of 60° S decreased by 0.2 between 2017 and 2070, equivalent to a 50% increase in the concentration of hydrogen ions since the pre-industrial period1."}, } @article {pmid30018126, year = {2018}, author = {Mann, A}, title = {Core Concept: Amazingly precise optical atomic clocks are more than timekeepers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7449-7451}, pmid = {30018126}, issn = {1091-6490}, } @article {pmid30018065, year = {2018}, author = {He, H and Yee, CH and McNally, DE and Simonson, JW and Zellman, S and Klemm, M and Kamenov, P and Geschwind, G and Zebro, A and Ghose, S and Bai, J and Dooryhee, E and Kotliar, G and Aronson, MC}, title = {Combined computational and experimental investigation of the La2CuO4-x S x (0 ≤ x ≤ 4) quaternary system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7890-7895}, pmid = {30018065}, issn = {1091-6490}, abstract = {The lack of a mechanistic framework for chemical reactions forming inorganic extended solids presents a challenge to accelerated materials discovery. We demonstrate here a combined computational and experimental methodology to tackle this problem, in which in situ X-ray diffraction measurements monitor solid-state reactions and deduce reaction pathways, while theoretical computations rationalize reaction energetics. The method has been applied to the La2CuO4-x S x (0 ≤ x ≤ 4) quaternary system, following an earlier prediction that enhanced superconductivity could be found in these new lanthanum copper(II) oxysulfide compounds. In situ diffraction measurements show that reactants containing Cu(II) and S(2-) ions undergo redox reactions, leaving their ions in oxidation states that are incompatible with forming the desired new compounds. Computations of the reaction energies confirm that the observed synthetic pathways are indeed favored over those that would hypothetically form the suggested compounds. The consistency between computation and experiment in the La2CuO4-x S x system suggests a role for predictive theory: to identify and to explicate new synthetic routes for forming predicted compounds.}, } @article {pmid30018064, year = {2018}, author = {Hazzi, NA and Moreno, JS and Ortiz-Movliav, C and Palacio, RD}, title = {Biogeographic regions and events of isolation and diversification of the endemic biota of the tropical Andes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7985-7990}, pmid = {30018064}, issn = {1091-6490}, mesh = {Biota/*physiology ; *Models, Biological ; Phylogeography ; South America ; }, abstract = {Understanding the spatial and temporal evolution of biota in the tropical Andes is a major challenge, given the region's topographic complexity and high beta diversity. We used a network approach to find biogeographic regions (bioregions) based on high-resolution species distribution models for 151 endemic bird taxa. Then, we used dated molecular phylogenies of 14 genera to reconstruct the area history through a sequence of allopatric speciation processes. We identified 15 biogeographical regions and found 26 events of isolation and diversification within their boundaries that are independently confirmed with disjunct distributions of sister taxa. Furthermore, these events are spatially congruent with six geographical barriers related to warm and/or dry river valleys, discontinuities in elevation, and high peaks separating fauna from different range slopes. The most important barrier is the Marañon River Valley, which limits the boundaries of four bioregions and is congruent with eight phylogenetic distribution breaks, separating the Central and Northern Andes, where the most bioregions are found. We also show that many bioregions have diffuse and overlapping structures, with contact and transition zones that challenge previous conceptions of biogeographical regions as spatially simple in structure. This study found evidence that the drivers of our identified bioregions were processes of Andean uplift and mountain dispersal facilitated by temperature oscillations of the Pleistocene. Therefore, Andean bioregions were not formed from one simple biogeographical event in a certain time frame, but from a combination of vicariance and dispersal events, which occurred in different time periods.}, } @article {pmid30018063, year = {2018}, author = {Rohde, JA and Roopnarine, O and Thomas, DD and Muretta, JM}, title = {Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {E7486-E7494}, pmid = {30018063}, issn = {1091-6490}, support = {R01 AR032961/AR/NIAMS NIH HHS/United States ; R42 DA037622/DA/NIDA NIH HHS/United States ; }, mesh = {Actins/*metabolism ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Allosteric Regulation/drug effects ; Benzylamines/*pharmacology/therapeutic use ; Cardiac Myosins/chemistry/*metabolism ; Cardiomyopathy, Hypertrophic, Familial/*drug therapy/etiology ; Humans ; Kinetics ; Myosin Subfragments/chemistry/*metabolism ; Protein Stability/drug effects ; Uracil/*analogs & derivatives/pharmacology/therapeutic use ; }, abstract = {We used transient biochemical and structural kinetics to elucidate the molecular mechanism of mavacamten, an allosteric cardiac myosin inhibitor and a prospective treatment for hypertrophic cardiomyopathy. We find that mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin not found in the single-headed S1 myosin motor fragment. We determined this by measuring cardiac myosin actin-activated and actin-independent ATPase and single-ATP turnover kinetics. A two-headed myosin fragment exhibits distinct autoinhibited ATP turnover kinetics compared with a single-headed fragment. Mavacamten enhanced this autoinhibition. It also enhanced autoinhibition of ADP release. Furthermore, actin changes the structure of the autoinhibited state by forcing myosin lever-arm rotation. Mavacamten slows this rotation in two-headed myosin but does not prevent it. We conclude that cardiac myosin is regulated in solution by an interaction between its two heads and propose that mavacamten stabilizes this state.}, } @article {pmid30018062, year = {2018}, author = {Smith, LJ and Wright, J and Clark, G and Ul-Hasan, T and Jin, X and Fong, A and Chandra, M and St Martin, T and Rubin, H and Knowlton, D and Ellsworth, JL and Fong, Y and Wong, KK and Chatterjee, S}, title = {Stem cell-derived clade F AAVs mediate high-efficiency homologous recombination-based genome editing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7379-E7388}, pmid = {30018062}, issn = {1091-6490}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; R01 HL087285/HL/NHLBI NIH HHS/United States ; }, mesh = {BRCA2 Protein/physiology ; Dependovirus/*genetics ; *Gene Editing ; Genetic Vectors ; Hematopoietic Stem Cells/*metabolism ; *Homologous Recombination ; Humans ; Interleukin Receptor Common gamma Subunit/genetics ; K562 Cells ; }, abstract = {The precise correction of genetic mutations at the nucleotide level is an attractive permanent therapeutic strategy for human disease. However, despite significant progress, challenges to efficient and accurate genome editing persist. Here, we report a genome editing platform based upon a class of hematopoietic stem cell (HSC)-derived clade F adeno-associated virus (AAV), which does not require prior nuclease-mediated DNA breaks and functions exclusively through BRCA2-dependent homologous recombination. Genome editing is guided by complementary homology arms and is highly accurate and seamless, with no evidence of on-target mutations, including insertion/deletions or inclusion of AAV inverted terminal repeats. Efficient genome editing was demonstrated at different loci within the human genome, including a safe harbor locus, AAVS1, and the therapeutically relevant IL2RG gene, and at the murine Rosa26 locus. HSC-derived AAV vector (AAVHSC)-mediated genome editing was robust in primary human cells, including CD34+ cells, adult liver, hepatic endothelial cells, and myocytes. Importantly, high-efficiency gene editing was achieved in vivo upon a single i.v. injection of AAVHSC editing vectors in mice. Thus, clade F AAV-mediated genome editing represents a promising, highly efficient, precise, single-component approach that enables the development of therapeutic in vivo genome editing for the treatment of a multitude of human gene-based diseases.}, } @article {pmid30018061, year = {2018}, author = {Sun, EW and De Camilli, P}, title = {Kv2 potassium channels meet VAP.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7849-7851}, pmid = {30018061}, issn = {1091-6490}, support = {T32 GM007223/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Potassium Channels, Voltage-Gated ; *Shab Potassium Channels ; }, } @article {pmid30018060, year = {2018}, author = {Guerra-Castellano, A and Díaz-Quintana, A and Pérez-Mejías, G and Elena-Real, CA and González-Arzola, K and García-Mauriño, SM and De la Rosa, MA and Díaz-Moreno, I}, title = {Oxidative stress is tightly regulated by cytochrome c phosphorylation and respirasome factors in mitochondria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7955-7960}, pmid = {30018060}, issn = {1091-6490}, mesh = {Animals ; Caspase 3/genetics/metabolism ; Cattle ; Cell Line ; Cytochromes c/genetics/*metabolism ; Electron Transport Complex IV/*metabolism ; Humans ; Mitochondria/*enzymology/genetics ; *Mutation ; Neoplasm Proteins/genetics/metabolism ; *Oxidative Stress ; Phosphorylation ; Rabbits ; }, abstract = {Respiratory cytochrome c has been found to be phosphorylated at tyrosine 97 in the postischemic brain upon neuroprotective insulin treatment, but how such posttranslational modification affects mitochondrial metabolism is unclear. Here, we report the structural features and functional behavior of a phosphomimetic cytochrome c mutant, which was generated by site-specific incorporation at position 97 of p-carboxymethyl-l-phenylalanine using the evolved tRNA synthetase method. We found that the point mutation does not alter the overall folding and heme environment of cytochrome c, but significantly affects the entire oxidative phosphorylation process. In fact, the electron donation rate of the mutant heme protein to cytochrome c oxidase, or complex IV, within respiratory supercomplexes was higher than that of the wild-type species, in agreement with the observed decrease in reactive oxygen species production. Direct contact of cytochrome c with the respiratory supercomplex factor HIGD1A (hypoxia-inducible domain family member 1A) is reported here, with the mutant heme protein exhibiting a lower affinity than the wild-type species. Interestingly, phosphomimetic cytochrome c also exhibited a lower caspase-3 activation activity. Altogether, these findings yield a better understanding of the molecular basis for mitochondrial metabolism in acute diseases, such as brain ischemia, and thus could allow the use of phosphomimetic cytochrome c as a neuroprotector with therapeutic applications.}, } @article {pmid30017824, year = {2018}, author = {Tripp, EA and Zhuang, Y and Schreiber, M and Stone, H and Berardi, AE}, title = {Evolutionary and ecological drivers of plant flavonoids across a large latitudinal gradient.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {147-161}, doi = {10.1016/j.ympev.2018.07.004}, pmid = {30017824}, issn = {1095-9513}, abstract = {Flavonoids are important secondary metabolites that play an integral role in protecting plants against UV radiation and other forms of environmental stress. Given widespread impacts of environmental effects associated with latitude on a multitude of biological systems and a well-documented increase in solar radiation towards the equator, plant flavonoid production is expected to increase as a response to factors associated with decreasing latitude. Using data from a Neotropical genus (Ruellia) that spans an exceptionally broad latitudinal gradient, we tested a hypothesis of a positive latitudinal gradient in flavonoid concentration and assessed other factors that influence flavonoid production including habitat type (xeric vs. wet), altitude, phylogenetic relatedness, and pleiotropic effects. Two flavones with peak absorbance in ultraviolet wavelengths, apigenin and luteolin, were detected across all species. Transcriptome data confirm high expression of the gene required for flavone biosynthesis, flavone synthase (FNS). Contrary to our prediction, data revealed a positive correlation between flavone concentration and higher latitudes. Further, we recovered strong impacts of xeric habitat, pleiotropy, and phylogenetic relatedness on flavone concentrations. This study documents a complex interplay of ecological, historical, phylogenetic relatedness, and pleiotropic factors driving plant flavonoid production.}, } @article {pmid30017823, year = {2018}, author = {Chesser, RT and Vaseghi, H and Hosner, PA and Bergner, LM and Cortes-Rodriguez, MN and Welch, AJ and Collins, CT}, title = {Molecular systematics of swifts of the genus Chaetura (Aves: Apodiformes: Apodidae).}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {162-171}, doi = {10.1016/j.ympev.2018.07.006}, pmid = {30017823}, issn = {1095-9513}, abstract = {Phylogenetic relationships among swifts of the morphologically conservative genus Chaetura were studied using mitochondrial and nuclear DNA sequences. Taxon sampling included all species and 21 of 30 taxa (species and subspecies) within Chaetura. Our results indicate that Chaetura is monophyletic and support the division of the genus into the two subgenera previously identified using plumage characters. However, our genetic data, when considered in combination with phenotypic data, appear to be at odds with the current classification of some species of Chaetura. We recommend that C. viridipennis, currently generally treated as specifically distinct from C. chapmani, be returned to its former status as C. chapmani viridipennis, and that C. andrei, now generally regarded as synonymous with C. vauxi aphanes, again be recognized as a valid species. Widespread Neotropical species C. spinicaudus is paraphyletic with respect to more range-restricted species C. fumosa, C. egregia, and C. martinica. Geographically structured genetic variation within some other species of Chaetura, especially notable in C. cinereiventris, suggests that future study may lead to recognition of additional species in this genus. Biogeographic analysis indicated that Chaetura originated in South America and identified several dispersal events to Middle and North America following the formation of the Isthmus of Panama.}, } @article {pmid30017651, year = {2018}, author = {Koepfli, C and Yan, G}, title = {Complex Determination of the Gametocyte Conversion Rate.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {634-635}, doi = {10.1016/j.pt.2018.06.005}, pmid = {30017651}, issn = {1471-5007}, mesh = {Humans ; *Malaria, Falciparum ; *Plasmodium falciparum ; }, } @article {pmid30017604, year = {2018}, author = {Atukorala, ADS and Franz-Odendaal, TA}, title = {Genetic linkage between altered tooth and eye development in lens-ablated Astyanax mexicanus.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {235-241}, doi = {10.1016/j.ydbio.2018.07.008}, pmid = {30017604}, issn = {1095-564X}, mesh = {Animals ; Anterior Eye Segment/abnormalities/embryology ; *Characiformes/embryology/genetics ; Disease Models, Animal ; Eye Abnormalities/embryology/genetics ; Eye Diseases, Hereditary ; *Fish Proteins/biosynthesis/genetics ; *Gene Expression Regulation, Developmental ; *Genetic Linkage ; Lens, Crystalline/*embryology/pathology ; Tooth/*embryology ; }, abstract = {The phenotype of lens-ablated Mexican tetra (Astyanax mexicanus) compared to wild-type surface fish has been described and includes, among other effects, eye degeneration, changes in tooth number and cranial bone changes. Here, we investigate the spatiotemporal expression patterns of several key genes involved in the development of these structures. Specifically, we show that the expression of pitx2, bmp4 and shh is altered in the eye, oral jaw, nasal pit and forebrain in these lens-ablated fish. Furthermore, for the first time, we show altered pitx2 expression in the cavefish, which also has altered eye and tooth phenotypes. We thus provide evidence for a genetic linkage between the eye and tooth modules in this fish species. Furthermore, the altered pitx2 expression pattern, together with the described morphological features of the lens-ablated fish suggests that Astyanax mexicanus could be considered as an alternative teleost model organism in which to study Axenfeld-Rieger syndrome (ARS), a rare autosomal dominant developmental disorder that is associated with PITX2 and which has both ocular and non-ocular abnormalities.}, } @article {pmid30017313, year = {2018}, author = {Cao, H and Wahlestedt, C and Kapranov, P}, title = {Strategies to Annotate and Characterize Long Noncoding RNAs: Advantages and Pitfalls.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {9}, pages = {704-721}, doi = {10.1016/j.tig.2018.06.002}, pmid = {30017313}, issn = {0168-9525}, abstract = {The past decade has seen an explosion of interest in long noncoding RNAs (lncRNAs). However, despite the massive volume of scientific data implicating these transcripts in a plethora of molecular and cellular processes, a great deal of controversy surrounds these RNAs. One of the main reasons for this lies in the multiple unique features of lncRNAs which limit the available methods used to characterize them. Combined with their vast numbers and inadequate classification, comprehensive annotation of these transcripts becomes a daunting task. The solution to this complex challenge likely lies in deep understanding of the strengths and weaknesses of each computational and empirical approach, and integration of multiple strategies to reduce noise, authenticate the results, and classify lncRNAs. We review here both the advantages and caveats of strategies commonly used for functional characterization and annotation of lncRNAs in the context of emerging conceptual guidelines for their application.}, } @article {pmid30017312, year = {2018}, author = {Krause, HM}, title = {New and Prospective Roles for lncRNAs in Organelle Formation and Function.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {10}, pages = {736-745}, doi = {10.1016/j.tig.2018.06.005}, pmid = {30017312}, issn = {0168-9525}, abstract = {The observation that long noncoding RNAs (lncRNAs) represent the majority of transcripts in humans has led to a rapid increase in interest and study. Most of this interest has focused on their roles in the nucleus. However, increasing evidence is beginning to reveal even more functions outside the nucleus, and even outside cells. Many of these roles are mediated by newly discovered properties, including the ability of lncRNAs to interact with lipids, membranes, and disordered protein domains, and to form differentially soluble RNA-protein sub-organelles. This review explores the possibilities enabled by these new properties and abilities, such as likely roles in exosome formation and function.}, } @article {pmid30017247, year = {2018}, author = {Bahn, M and Ingrisch, J}, title = {Accounting for Complexity in Resilience Comparisons: A Reply to Yeung and Richardson, and Further Considerations.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {649-651}, doi = {10.1016/j.tree.2018.06.006}, pmid = {30017247}, issn = {1872-8383}, mesh = {*Conservation of Natural Resources ; *Ecosystem ; }, } @article {pmid30017175, year = {2018}, author = {Hammond, AS and Almécija, S and Libsekal, Y and Rook, L and Macchiarelli, R}, title = {A partial Homo pelvis from the Early Pleistocene of Eritrea.}, journal = {Journal of human evolution}, volume = {123}, number = {}, pages = {109-128}, doi = {10.1016/j.jhevol.2018.06.010}, pmid = {30017175}, issn = {1095-8606}, abstract = {Here we analyze 1.07-0.99 million-year-old pelvic remains UA 173/405 from Buia, Eritrea. Based on size metrics, UA 173/405 is likely associated with an already described pubic symphysis (UA 466) found nearby. The morphology of UA 173/405 was quantitatively characterized using three-dimensional landmark-based morphometrics and linear data. The Buia specimen falls within the range of variation of modern humans for all metrics investigated, making it unlikely that the shared last common ancestor of Late Pleistocene Homo species would have had an australopith-like pelvis. The discovery of UA 173/405 adds to the increasing number of fossils suggesting that the postcranial morphology of Homo erectus s.l. was variable and, in some cases, nearly indistinguishable from modern human morphology. This Eritrean fossil demonstrates that modern human-like pelvic morphology may have had origins in the Early Pleistocene, potentially within later African H. erectus.}, } @article {pmid30017000, year = {2018}, author = {Assefa, GA and Kelkay, MZ}, title = {Goat pasteurellosis: serological analysis of circulating Pasteurella serotypes in Tanqua Aberegelle and Kola Tembien Districts, Northern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {485}, pmid = {30017000}, issn = {1756-0500}, mesh = {Animals ; Cross-Sectional Studies ; Ethiopia ; Goats/*microbiology ; Pasteurella/immunology/*isolation & purification ; Pasteurella Infections/*veterinary ; *Serogroup ; Serotyping ; }, abstract = {OBJECTIVES: A cross-sectional study was employed with the aim to explore the serological status of goats; we evaluated the presence of serum antibodies of the circulating serotypes of the genus Pasteurella. A total of 124 serum samples were collected from randomly selected goats and subsequently serotyped using indirect haemagglutination test.

RESULTS: In the current study, the overall prevalence of pasteurellosis in goats was 31.4%. Additionally, a total of eight serotypes of Pasteurella were serotyped. It is evident that 25% out of 124 sampled animals were found infected by four or more circulating serotypes and 6.4% animals were also found positive for all serotypes. Accordingly, the prevalence of Pasteurella multocida serotype A were 16.9%, Mannheimia haemolytica serotype A1 26.6%, M. haemolytica serotype A2 18.5%, M. haemolytica serotype A7 16.1%, Bibersteinia trehalosi serotype T3 20.9%, B. trehalosi serotype T4 21.7%, B. trehalosi serotype T10 27.4%, and B. trehalosi serotype T15 was 25.8%. Therefore, although there has been vaccination campaign with monovalent vaccine P. multocida type A, the diseases still exerts negative impacts through death of goats to smallholder farmers. Therefore, to control the disease the government should provide multivalent vaccine of the above serotypes.}, } @article {pmid30016992, year = {2018}, author = {Doostparast Torshizi, A and Duan, J and Wang, K}, title = {Transcriptional network analysis on brains reveals a potential regulatory role of PPP1R3F in autism spectrum disorders.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {489}, pmid = {30016992}, issn = {1756-0500}, support = {R01 MH094714/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; MH108728//National Institutes of Health/ ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R01 MH106575/MH/NIMH NIH HHS/United States ; R01 MH105472/MH/NIMH NIH HHS/United States ; R01 MH108728/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; }, mesh = {Autism Spectrum Disorder/*genetics ; Brain/metabolism ; Carrier Proteins/*genetics ; *Gene Regulatory Networks ; Humans ; Phosphoprotein Phosphatases/*genetics ; Transcriptome ; }, abstract = {OBJECTIVE: This study aims at identifying master regulators of transcriptional networks in autism spectrum disorders (ASDs).

RESULTS: With two sets of independent RNA-Seq data generated on cerebellum from patients with ASDs and control subjects (N = 39 and 45 for set 1, N = 24 and 38 for set 2, respectively), we carried out a network deconvolution of transcriptomic data, followed by virtual protein activity analysis. We identified PPP1R3F (Protein Phosphatase 1 Regulatory Subunit 3F) as a candidate master regulator affecting a large body of downstream genes that are associated with the disease phenotype. Pathway analysis on the identified targets of PPP1R3F in both datasets indicated alteration of endocytosis pathway. Despite a limited sample size, our study represents one of the first applications of network deconvolution approach to brain transcriptomic data to generate hypotheses that may be further validated by large-scale studies.}, } @article {pmid30016990, year = {2018}, author = {Sedghamiz, H and Morris, M and Craddock, TJA and Whitley, D and Broderick, G}, title = {High-fidelity discrete modeling of the HPA axis: a study of regulatory plasticity in biology.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {76}, pmid = {30016990}, issn = {1752-0509}, support = {GW093042//Congressionally Directed Medical Research Programs/ ; GW140142//Congressionally Directed Medical Research Programs/ ; }, abstract = {BACKGROUND: The hypothalamic-pituitary-adrenal (HPA) axis is a central regulator of stress response and its dysfunction has been associated with a broad range of complex illnesses including Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS). Though classical mathematical approaches have been used to model HPA function in isolation, its broad regulatory interactions with immune and central nervous function are such that the biological fidelity of simulations is undermined by the limited availability of reliable parameter estimates.

METHOD: Here we introduce and apply a generalized discrete formalism to recover multiple stable regulatory programs of the HPA axis using little more than connectivity between physiological components. This simple discrete model captures cyclic attractors such as the circadian rhythm by applying generic constraints to a minimal parameter set; this is distinct from Ordinary Differential Equation (ODE) models, which require broad and precise parameter sets. Parameter tuning is accomplished by decomposition of the overall regulatory network into isolated sub-networks that support cyclic attractors. Network behavior is simulated using a novel asynchronous updating scheme that enforces priority with memory within and between physiological compartments.

RESULTS: Consistent with much more complex conventional models of the HPA axis, this parsimonious framework supports two cyclic attractors, governed by higher and lower levels of cortisol respectively. Importantly, results suggest that stress may remodel the stability landscape of this system, favoring migration from one stable circadian cycle to the other. Access to each regime is dependent on HPA axis tone, captured here by the tunable parameters of the multi-valued logic. Likewise, an idealized glucocorticoid receptor blocker alters the regulatory topology such that maintenance of persistently low cortisol levels is rendered unstable, favoring a return to normal circadian oscillation in both cortisol and glucocorticoid receptor expression.

CONCLUSION: These results emphasize the significance of regulatory connectivity alone and how regulatory plasticity may be explored using simple discrete logic and minimal data compared to conventional methods.}, } @article {pmid30016985, year = {2018}, author = {Deculllier, E and Maisonneuve, H}, title = {Correcting the literature: Improvement trends seen in contents of retraction notices.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {490}, pmid = {30016985}, issn = {1756-0500}, mesh = {Biomedical Research ; *Periodicals as Topic ; Plagiarism ; Publications ; *Retraction of Publication as Topic ; }, abstract = {OBJECTIVE: To analyse retraction notices from 2016 and compare their quality to the 2008 notices.

RESULTS: From 146 retractions retrieved, only 123 were included, of which, a clear reason for retraction was available for 122 (99.2%) and no reason was given for one (0.8%). The main reasons for retraction were mistakes 26.0% (n = 32), fraud 26.0% (n = 32), plagiarism 20.3% (n = 25), and overlap 8.1% (n = 10). In 100 (81.3%) cases, a mention of retraction was available on the original paper, in 15 (12.2%) there was no mention of retraction, and 8 (6.5%) papers were deleted. Compared to the previous cohorts, management of retraction has improved because 99.2% provided a clear reason, and 81.3% of original articles were available with a mention of the retraction.}, } @article {pmid30016984, year = {2018}, author = {Nkuwi, EJ and Kabanangi, F and Joachim, A and Rugarabamu, S and Majigo, M}, title = {Methicillin-resistant Staphylococcus aureus contamination and distribution in patient's care environment at Muhimbili National Hospital, Dar es Salaam-Tanzania.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {484}, pmid = {30016984}, issn = {1756-0500}, mesh = {*Cross Infection ; Cross-Sectional Studies ; Hospitals ; Humans ; Methicillin ; Methicillin-Resistant Staphylococcus aureus/*isolation & purification ; *Staphylococcal Infections ; Tanzania ; }, abstract = {OBJECTIVE: Environmental contamination with methicillin-resistant Staphylococcus aureus in routine medical care settings poses an increased risk of health care associated infections through cross-transmission. This study aimed at determining the magnitude and distribution of methicillin-resistant S. aureus contamination among various items in patients' care surroundings at Muhimbili National Hospital, Tanzania's largest tertiary hospital.

RESULTS: A total of 200 environmental samples from high touch items were processed and out of these methicillin-resistant S. aureus was 19.5% with significantly higher contamination in general wards. Patients' beds surfaces were the most contaminated among studied items (43.7%), whilst the surgical trolleys were least contaminated (7.7%). Presence of 10 or more patients in a room was an important significant correlate for methicillin-resistant S. aureus contamination by bivariate logistic regression model (odds ratio: 4.75, 95% confidence interval 1.624-13.895, p = 0.004). These findings warrant further study of decontamination practices and improved infection control mechanisms, especially in light of the drug resistant isolates identified.}, } @article {pmid30016979, year = {2018}, author = {Hall, JA and Stephenson, J and Barrett, G}, title = {Comparing the order of the London Measure of Unplanned Pregnancy and the Demographic and Health Survey question on pregnancy intention in a single group of postnatal women in Malawi - the effect of question order on assessment of pregnancy intention.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {487}, pmid = {30016979}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; 097268/Z/11/Z//Wellcome Trust/United Kingdom ; }, mesh = {Female ; Health Surveys ; Humans ; *Intention ; Malawi ; Parity ; Pregnancy ; *Pregnancy, Unplanned ; }, abstract = {OBJECTIVE: To investigate the effect of question order on women's responses to the London Measure of Unplanned Pregnancy (LMUP) or the pregnancy intention question of the Demographic and Health Survey (DHS) when both are asked in the same survey. We collected data on pregnancy intention from a cohort of 4244 pregnant women in Malawi who were re-interviewed at 1, 6 and 12 months postnatally. Women in Zone 1 were asked the LMUP, then antenatal questions, then the DHS pregnancy intention question, women in Zone 2 were asked the DHS pregnancy intention question, then antenatal questions, then the LMUP; women in Zone 3 were only asked the DHS pregnancy intention question. We used linear regression to compare the LMUP score and ordinal regression to compare DHS categorisations of pregnancy intention across Zones, adjusting for baseline socioeconomic differences between the Zones.

RESULTS: We found no effect of question order on the assessment of pregnancy intention by the LMUP. There were differences in the assessment of pregnancy intention when the pregnancy intention question in the DHS was used, however this seemed to be due to baseline sociodemographic differences between the groups of pregnant women being compared, and not due to question order.}, } @article {pmid30016976, year = {2018}, author = {Khadka, P and Basnet, RB and Rijal, BP and Sherchand, JB}, title = {Pulmonary nocardiosis masquerading renascence of tuberculosis in an immunocompetent host: a case report from Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {488}, pmid = {30016976}, issn = {1756-0500}, mesh = {Diagnosis, Differential ; Farmers ; Humans ; Immunocompromised Host ; Male ; Middle Aged ; Nepal ; Nocardia/isolation & purification ; Nocardia Infections/*diagnosis ; Tuberculosis, Pulmonary/*diagnosis ; }, abstract = {BACKGROUND: Pulmonary nocardiosis is an opportunistic infection in an immunocompromised patient; however, often neglected in the immunocompetent patient from the diagnosis considerations.

CASE PRESENTATIONS: We describe a case of pulmonary nocardiosis masquerading renascence of tuberculosis, in a 51-years-Nepali farmer. After a 6 month of presumed successful antitubercular therapy; the patient develops the clinical presentations and radiological features showing similarities with that of tuberculosis and malignancy. MTB complex was not detected with Xpert MTB/RIF assay and cytological examinations were negative for the malignant cells, however. The Ziehl-Neelsen staining of the broncho-alveolar-lavage revealed acid-fast, thin branching filamentous organisms suggestive Nocardia spp. Further, identifications and susceptibility pattern against recommended antibiotics were assessed as per the CLSI guidelines. The case was then, subsequently, diagnosed as pulmonary nocardiosis. Trimethoprim-sulfamethoxazole was prescribed for 12 months. The patient underwent progressive changes and no relapse was noted in a periodic follow-up.

CONCLUSIONS: This case underscores that pulmonary nocardiosis requires diagnostic considerations, regardless of a patient's immunologic status and other mimicking infections.}, } @article {pmid30016972, year = {2018}, author = {Kargarpour Kamakoli, M and Khanipour, S and Hadifar, S and Ghajavand, H and Farmanfarmaei, G and Fateh, A and Siadat, SD and Vaziri, F}, title = {Challenge in direct Spoligotyping of Mycobacterium tuberculosis: a problematic issue in the region with high prevalence of polyclonal infections.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {486}, pmid = {30016972}, issn = {1756-0500}, mesh = {Bacterial Typing Techniques ; Genotype ; Humans ; Iran ; Mycobacterium tuberculosis/*genetics/isolation & purification ; Prevalence ; Tuberculosis ; *Tuberculosis, Pulmonary ; }, abstract = {OBJECTIVE: Based on our recent studies the prevalence of polyclonal infection in tuberculosis clinical specimens is more than 50% in Tehran, Iran. With this background, Spoligotyping was performed on clinical specimens and their respective cultures, and we examined whether mixed infections interfere with the results or not.

RESULTS: Based on the Spoligotyping pattern, among the fourteen patients, 57.1% had different genotypes in clinical samples and their respective cultures. These discrepant patterns were suggestive of polyclonal infections in clinical samples with possible overlapping Spoligotype patterns. We propose that in societies with high mixed infections (e.g. Iran), direct Spoligotyping on clinical samples can be controversial.}, } @article {pmid30016955, year = {2018}, author = {Habel, JC and Husemann, M and Ulrich, W}, title = {Evolution of contact and alarm calls in the Kenyan endemic Hinde's babbler (Aves: Passeriformes).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {112}, pmid = {30016955}, issn = {1471-2148}, mesh = {Altitude ; Analysis of Variance ; Animals ; *Biological Evolution ; Ecosystem ; Geography ; Kenya ; Passeriformes/*physiology ; Principal Component Analysis ; *Social Behavior ; Vocalization, Animal/*physiology ; }, abstract = {BACKGROUND: Spatial isolation, diverging environmental conditions and social structures may lead to the differentiation of various traits, e.g. molecules, morphology and behaviour. Bird calls may provide important information on effects of geographic isolation and may reflect diverging ecological conditions related to altitude. Furthermore, bird calls are strongly shaped by the social behaviour of species. The Kenyan endemic bird Hinde's Babbler, Turdoides hindei, is a cooperative breeder existing in distinct family groups. The species occurs in five isolated population groups at different altitudes across its distribution range in south-eastern Kenya. With this model species we test for potential effects of geographic isolation, diverging altitudes, and social structures. We recorded and analysed contact and alarm calls of T. hindei, including its entire distribution range and all existing population groups.

RESULTS: Our data show significant differentiation of call characteristics among population groups across the species' distribution range. This differentiation is correlated with geographical distance, but also with altitude. We also found strong call differentiation among neighbouring family groups. Call differentiation of contact calls was comparatively high in comparison to alarm calls, which showed a lower degree of divergence.

CONCLUSION: Our data show that call differentiation is governed by geographic isolation as well as altitude. Diverging degrees of call differentiation in contact and alarm calls suggests that both call types are under different selective pressures. Alarm calls are required to be understood by all members of the species across the entire distribution range and thus call differentiation is lower. In contrast, contact calls are more specific and differ even among neighbouring families supporting the maintenance of distinct bird families and groups.}, } @article {pmid30016953, year = {2018}, author = {Guan, DL and Ma, LB and Khan, MS and Zhang, XX and Xu, SQ and Xie, JY}, title = {Analysis of codon usage patterns in Hirudinaria manillensis reveals a preference for GC-ending codons caused by dominant selection constraints.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {542}, pmid = {30016953}, issn = {1471-2164}, support = {S2015YB03//Excellent Doctor Innovation Project of Shaanxi Normal University/ ; 2016TS057//Fundamental Research Funds for the Central Universities/ ; GK201604008//Fundamental Research Funds for the Central Universities/ ; GK201702010//Fundamental Research Funds for the Central Universities/ ; GK201701006//Fundamental Research Funds for the Central Universities/ ; 61673251//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Base Composition ; *Codon ; *Evolution, Molecular ; Gene Expression ; Genome ; Leeches/*genetics/metabolism ; Nucleotides/analysis ; Principal Component Analysis ; Proteins/chemistry/genetics ; *Selection, Genetic ; }, abstract = {BACKGROUND: Hirudinaria manillensis is an ephemeral, blood-sucking ectoparasite, possessing anticoagulant capacities with potential medical applications. Analysis of codon usage patterns would contribute to our understanding of the evolutionary mechanisms and genetic architecture of H. manillensis, which in turn would provide insight into the characteristics of other leeches. We analysed codon usage and related indices using 18,000 coding sequences (CDSs) retrieved from H. manillensis RNA-Seq data.

RESULTS: We identified four highly preferred codons in H. manillensis that have G/C-endings. Points generated in an effective number of codons (ENC) plot distributed below the standard curve and the slope of a neutrality plot was less than 1. Highly expressed CDSs had lower ENC content and higher GC content than weakly expressed CDSs. Principal component analysis conducted on relative synonymous codon usage (RSCU) values divided CDSs according to GC content and divided codons according to ending bases. Moreover, by determining codon usage, we found that the majority of blood-diet related genes have undergone less adaptive evolution in H. manillensis, except for those with homologous sequences in the host species.

CONCLUSIONS: Codon usage in H. manillensis had an overall preference toward C-endings and indicated that codon usage patterns are mediated by differential expression, GC content, and biological function. Although mutation pressure effects were also notable, the majority of genetic evolution in H. manillensis was driven by natural selection.}, } @article {pmid30016951, year = {2018}, author = {Liu, GS and Ballweg, R and Ashbaugh, A and Zhang, Y and Facciolo, J and Cushion, MT and Zhang, T}, title = {A quantitative systems pharmacology (QSP) model for Pneumocystis treatment in mice.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {77}, pmid = {30016951}, issn = {1752-0509}, support = {I01 BX000523/BX/BLRD VA/United States ; I01BX000523//U.S. Department of Veterans Affairs/ ; }, abstract = {BACKGROUND: The yeast-like fungi Pneumocystis, resides in lung alveoli and can cause a lethal infection known as Pneumocystis pneumonia (PCP) in hosts with impaired immune systems. Current therapies for PCP, such as trimethoprim-sulfamethoxazole (TMP-SMX), suffer from significant treatment failures and a multitude of serious side effects. Novel therapeutic approaches (i.e. newly developed drugs or novel combinations of available drugs) are needed to treat this potentially lethal opportunistic infection. Quantitative Systems Pharmacological (QSP) models promise to aid in the development of novel therapies by integrating available pharmacokinetic (PK) and pharmacodynamic (PD) knowledge to predict the effects of new treatment regimens.

RESULTS: In this work, we constructed and independently validated PK modules of a number of drugs with available pharmacokinetic data. Characterized by simple structures and well constrained parameters, these PK modules could serve as a convenient tool to summarize and predict pharmacokinetic profiles. With the currently accepted hypotheses on the life stages of Pneumocystis, we also constructed a PD module to describe the proliferation, transformation, and death of Pneumocystis. By integrating the PK module and the PD module, the QSP model was constrained with observed levels of asci and trophic forms following treatments with multiple drugs. Furthermore, the temporal dynamics of the QSP model were validated with corresponding data.

CONCLUSIONS: We developed and validated a QSP model that integrates available data and promises to facilitate the design of future therapies against PCP.}, } @article {pmid30016950, year = {2018}, author = {Couronné, R and Probst, P and Boulesteix, AL}, title = {Random forest versus logistic regression: a large-scale benchmark experiment.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {270}, pmid = {30016950}, issn = {1471-2105}, support = {BO3139/6-1//Deutsche Forschungsgemeinschaft/ ; BO3139/2-3//Deutsche Forschungsgemeinschaft/ ; }, abstract = {BACKGROUND AND GOAL: The Random Forest (RF) algorithm for regression and classification has considerably gained popularity since its introduction in 2001. Meanwhile, it has grown to a standard classification approach competing with logistic regression in many innovation-friendly scientific fields.

RESULTS: In this context, we present a large scale benchmarking experiment based on 243 real datasets comparing the prediction performance of the original version of RF with default parameters and LR as binary classification tools. Most importantly, the design of our benchmark experiment is inspired from clinical trial methodology, thus avoiding common pitfalls and major sources of biases.

CONCLUSION: RF performed better than LR according to the considered accuracy measured in approximately 69% of the datasets. The mean difference between RF and LR was 0.029 (95%-CI =[0.022,0.038]) for the accuracy, 0.041 (95%-CI =[0.031,0.053]) for the Area Under the Curve, and - 0.027 (95%-CI =[-0.034,-0.021]) for the Brier score, all measures thus suggesting a significantly better performance of RF. As a side-result of our benchmarking experiment, we observed that the results were noticeably dependent on the inclusion criteria used to select the example datasets, thus emphasizing the importance of clear statements regarding this dataset selection process. We also stress that neutral studies similar to ours, based on a high number of datasets and carefully designed, will be necessary in the future to evaluate further variants, implementations or parameters of random forests which may yield improved accuracy compared to the original version with default values.}, } @article {pmid30016947, year = {2018}, author = {Song, Z and Stajich, JE and Xie, Y and Liu, X and He, Y and Chen, J and Hicks, GR and Wang, G}, title = {Comparative analysis reveals unexpected genome features of newly isolated Thraustochytrids strains: on ecological function and PUFAs biosynthesis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {541}, pmid = {30016947}, issn = {1471-2164}, support = {IOS-1027542//National Science Foundation/ ; CA-R-PPA-5062-H//National Institute of Food and Agriculture Hatch project/ ; 31670044//National Natural Science Foundation of China/ ; 91751115//National Natural Science Foundation of China/ ; S10 OD016290/OD/NIH HHS/United States ; # 2016YFA0601401//The National Key Research Program of China/ ; 201305022//National Marine Public Welfare Industry Special Scientific Research Project/ ; }, mesh = {Biosynthetic Pathways/genetics ; Docosahexaenoic Acids/*biosynthesis ; Ecological and Environmental Phenomena ; Fatty Acids, Unsaturated/biosynthesis ; Gene Ontology ; *Genome ; Genomics ; Molecular Sequence Annotation ; Multigene Family ; Phylogeny ; Stramenopiles/classification/enzymology/*genetics/metabolism ; }, abstract = {BACKGROUND: Thraustochytrids are unicellular fungal-like marine protists with ubiquitous existence in marine environments. They are well-known for their ability to produce high-valued omega-3 polyunsaturated fatty acids (ω-3-PUFAs) (e.g., docosahexaenoic acid (DHA)) and hydrolytic enzymes. Thraustochytrid biomass has been estimated to surpass that of bacterioplankton in both coastal and oceanic waters indicating they have an important role in microbial food-web. Nevertheless, the molecular pathway and regulatory network for PUFAs production and the molecular mechanisms underlying ecological functions of thraustochytrids remain largely unknown.

RESULTS: The genomes of two thraustochytrids strains (Mn4 and SW8) with ability to produce DHA were sequenced and assembled with a hybrid sequencing approach utilizing Illumina short paired-end reads and Pacific Biosciences long reads to generate a highly accurate genome assembly. Phylogenomic and comparative genomic analyses found that DHA-producing thraustochytrid strains were highly similar and possessed similar gene content. Analysis of the conventional fatty acid synthesis (FAS) and the polyketide synthase (PKS) systems for PUFAs production only detected incomplete and fragmentary pathways in the genome of these two strains. Surprisingly, secreted carbohydrate active enzymes (CAZymes) were found to be significantly depleted in the genomes of these 2 strains as compared to other sequenced relatives. Furthermore, these two strains possess an expanded gene repertoire for signal transduction and self-propelled movement, which could be important for their adaptations to dynamic marine environments.

CONCLUSIONS: Our results demonstrate the possibility of a third PUFAs synthesis pathway besides previously described FAS and PKS pathways encoded in the genome of these two thraustochytrid strains. Moreover, lack of a complete set of hydrolytic enzymatic machinery for degrading plant-derived organic materials suggests that these two DHA-producing strains play an important role as a nutritional source rather than a nutrient-producer in marine microbial-food web. Results of this study suggest the existence of two types of saprobic thraustochytrids in the world's ocean. The first group, which does not produce cellulosic enzymes and live as 'left-over' scavenger of bacterioplankton, serves as a dietary source for the plankton of higher trophic levels and the other possesses capacity to live on detrital organic matters in the marine ecosystems.}, } @article {pmid30016940, year = {2018}, author = {Schrammel, B and Petzold, M and Cervero-Aragó, S and Sommer, R and Lück, C and Kirschner, A}, title = {Persistent presence of outer membrane epitopes during short- and long-term starvation of five Legionella pneumophila strains.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {75}, pmid = {30016940}, issn = {1471-2180}, abstract = {BACKGROUND: Legionella pneumophila, the causative agent of Legionnaire's disease, may enter a viable but non-culturable (VBNC) state triggered by environmental stress conditions. Specific outer-membrane epitopes of L. pneumophila are used in many diagnostic applications and some of them are linked to important virulence-related factors or endotoxins. However, it is not clear how the presence and status of these epitopes are influenced by environmental stress conditions. In this study, changes of outer membrane epitopes for monoclonal antibodies (mAb) from the Dresden panel and the major outer membrane protein MOMP were analysed for five L. pneumophila strains during short- and long-term starvation in ultrapure water.

RESULTS: With ELISA and single cell immuno-fluorescence analysis, we could show that for most of the investigated mAb-strain combinations the total number of mAb-stained Legionella cells stayed constant for up to 400 days. Especially the epitopes of mAb 3/1, 8/5, 26/1 and 20/1, which are specific for L. pneumophila serogroup 1 subtypes, and the mAb 9/1, specific for serogroup 6, showed long-term persistence. For most mAb- stained cells, a high percentage of viable cells was observed at least until 118 days of starvation. At the same time, we observed a reduction of the fluorescence intensity of the stained cells during starvation indicating a loss of epitopes from the cell surface. However, most of the epitopes, including the virulence-associated mAb 3/1 epitope were still present with high fluorescence intensity after 400 days of starvation in up to 50% of the starved L. pneumophila population.

CONCLUSIONS: The results demonstrate the continuous presence of outer membrane epitopes of L. pneumophila during short-term and long-term starvation. Thus, culture-independent mAb-based diagnostic and detection tools, such as immuno-magnetic separation and microarray techniques are applicable for both L. pneumophila in the culturable and the VBNC state even after long-term starvation but nevertheless require careful testing before application. However, the mere presence of those epitopes is not necessarily an indication of viability or infectivity.}, } @article {pmid30016933, year = {2018}, author = {Baheti, S and Tang, X and O'Brien, DR and Chia, N and Roberts, LR and Nelson, H and Boughey, JC and Wang, L and Goetz, MP and Kocher, JA and Kalari, KR}, title = {HGT-ID: an efficient and sensitive workflow to detect human-viral insertion sites using next-generation sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {271}, pmid = {30016933}, issn = {1471-2105}, support = {P50 CA116201/CA/NCI NIH HHS/United States ; U54 GM114838/GM/NIGMS NIH HHS/United States ; P50CA116201//Mayo Clinic Breast Specialized Program of Research Excellence/ ; U54GM114838//National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: Transfer of genetic material from microbes or viruses into the host genome is known as horizontal gene transfer (HGT). The integration of viruses into the human genome is associated with multiple cancers, and these can now be detected using next-generation sequencing methods such as whole genome sequencing and RNA-sequencing.

RESULTS: We designed a novel computational workflow, HGT-ID, to identify the integration of viruses into the human genome using the sequencing data. The HGT-ID workflow primarily follows a four-step procedure: i) pre-processing of unaligned reads, ii) virus detection using subtraction approach, iii) identification of virus integration site using discordant and soft-clipped reads and iv) HGT candidates prioritization through a scoring function. Annotation and visualization of the events, as well as primer design for experimental validation, are also provided in the final report. We evaluated the tool performance with the well-understood cervical cancer samples. The HGT-ID workflow accurately detected known human papillomavirus (HPV) integration sites with high sensitivity and specificity compared to previous HGT methods. We applied HGT-ID to The Cancer Genome Atlas (TCGA) whole-genome sequencing data (WGS) from liver tumor-normal pairs. Multiple hepatitis B virus (HBV) integration sites were identified in TCGA liver samples and confirmed by HGT-ID using the RNA-Seq data from the matched liver pairs. This shows the applicability of the method in both the data types and cross-validation of the HGT events in liver samples. We also processed 220 breast tumor WGS data through the workflow; however, there were no HGT events detected in those samples.

CONCLUSIONS: HGT-ID is a novel computational workflow to detect the integration of viruses in the human genome using the sequencing data. It is fast and accurate with functions such as prioritization, annotation, visualization and primer design for future validation of HGTs. The HGT-ID workflow is released under the MIT License and available at http://kalarikrlab.org/Software/HGT-ID.html .}, } @article {pmid30016932, year = {2018}, author = {El-Hawaz, RF and Grace, MH and Janbey, A and Lila, MA and Adelberg, JW}, title = {Correction to: In vitro mineral nutrition of Curcuma longa L. affects production of volatile compounds in rhizomes after transfer to the greenhouse.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {148}, pmid = {30016932}, issn = {1471-2229}, abstract = {Following publication of the original article [1], the author reported a formatting error and an error in the figure caption. The original article has been corrected. The details of the errors are as follows.}, } @article {pmid30016651, year = {2018}, author = {Geda, SR and Lujan, NK and Perkins, M and Abernethy, E and Sabaj, MH and Gangloff, M}, title = {Multilocus phylogeny of the zebra mussel family Dreissenidae (Mollusca: Bivalvia) reveals a fourth Neotropical genus sister to all other genera.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {1020-1033}, doi = {10.1016/j.ympev.2018.07.009}, pmid = {30016651}, issn = {1095-9513}, abstract = {Dreissenidae is one of the most economically and ecologically important families of freshwater and estuarine mollusks. Fourteen extant species and three genera are currently recognized: Congeria contains three species from karst caves along the eastern Adriatic coast and one from the Orinoco River of Venezuela, Dreissena contains six species native to Eastern European rivers and estuaries, and Mytilopsis contains three species from the Gulf of Mexico, Caribbean, and northwestern coast of South America and one from the Tocantins River of Brazil. Previous molecular phylogenetic studies have examined all species except those from South American rivers, and found each genus to be monophyletic with Congeria and Mytilopsis forming a clade sister to Dreissena. We present the first multilocus phylogeny of Dreissenidae inclusive of South American riverine species. Bayesian and maximum likelihood analyses of a 3085 bp alignment consisting of mitochondrial (COI and 16S) and nuclear (18S and 28S) gene regions found Neotropical species to be consistently and strongly supported as sister to all other dreissenids, although incomplete sequencing of the single Orinoco specimen obscured Neotropical monophyly. Our intergeneric relationships are inconsistent with an extensive fossil record suggesting that dreissenids originated in Europe approximately 30 My before dispersing to the Western Hemisphere. Fossil-calibrated analyses indicated that Neotropical dreissenids diverged from European lineages in the mid to late Eocene (∼39.3 Ma), and Brazilian and Guiana shield populations diversified during the Oligocene to Miocene. We erect the new genus Rheodreissena for all Neotropical freshwater dreissenids and present haplotype data indicative of at least three species. Widespread anthropogenic alteration of the middle Xingu River and lower Amazon threatens the persistence of these endemic, poorly studied mussels and may facilitate introduction beyond their native range.}, } @article {pmid30016640, year = {2018}, author = {Hong, CS and Saint-Jeannet, JP}, title = {The b-HLH transcription factor Hes3 participates in neural plate border formation by interfering with Wnt/β-catenin signaling.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {162-172}, pmid = {30016640}, issn = {1095-564X}, support = {R01 DE025468/DE/NIDCR NIH HHS/United States ; R01 DE025806/DE/NIDCR NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Cell Differentiation/physiology ; DNA-Binding Proteins/metabolism ; Embryo, Nonmammalian ; Embryonic Development ; Helix-Loop-Helix Motifs ; Neural Crest/cytology/embryology/metabolism ; Neural Plate/cytology/*embryology/*metabolism ; Phylogeny ; SOXB1 Transcription Factors/metabolism ; Wnt Signaling Pathway/*physiology ; Xenopus Proteins/genetics/*metabolism ; Xenopus laevis/*embryology/genetics/metabolism ; beta Catenin/*metabolism ; }, abstract = {Hes3 belongs to the Hes basic helix-loop-helix family of transcriptional repressors that play central roles in maintaining progenitor cells and regulating binary cell fate decisions in the embryo. During Xenopus laevis development, hes3 is expressed in the embryonic ectoderm in a horseshoe shape domain at the edge of the developing neural pate. Hes3 mis-expression at early neurula stage blocks neural crest (snai2, sox8, sox9 and sox10) and cranial placode (six1 and dmrta1) gene expression, and promotes neural plate (sox2 and sox3) fate. At tailbud stage, these embryos exhibited a massive up-regulation of both sox8 and sox10 expression, associated with an increase in genes important for melanocytes differentiation (mitf and dct). Using a hormone inducible construct we show that Hes3 does not induce a pigment cell differentiation program de novo, rather it maintains progenitor cells in an undifferentiated state, and as Hes3 expression subsides overtime these cells adopt a pigment cell fate. We demonstrate that mechanistically Hes3 mediates its activity through inhibition of Wnt/β-catenin signaling, a molecular pathway critical for neural crest specification and pigment cell lineage differentiation. We propose that Hes3 at the edge of the neural plate spatially restricts the response to mesoderm-derived Wnt ligands, thereby contributing to the establishment of sharp boundaries of gene expression at the neural plate border.}, } @article {pmid30016639, year = {2018}, author = {Yosef, N and Vadakkan, TJ and Park, JH and Poché, RA and Thomas, JL and Dickinson, ME}, title = {The phenotypic and functional properties of mouse yolk-sac-derived embryonic macrophages.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {138-154}, pmid = {30016639}, issn = {1095-564X}, support = {R01 EB016629/EB/NIBIB NIH HHS/United States ; R01 HL128064/HL/NHLBI NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Cell Culture Techniques/methods ; Cell Differentiation/physiology ; Coculture Techniques/methods ; Erythroid Precursor Cells/*physiology ; Flow Cytometry/methods ; Hematopoietic Stem Cells/physiology ; Macrophages/cytology/*physiology ; Mice/embryology ; Myeloid Progenitor Cells/*physiology ; Phenotype ; Yolk Sac/cytology ; }, abstract = {Macrophages are well characterized as immune cells. However, in recent years, a multitude of non-immune functions have emerged many of which play essential roles in a variety of developmental processes (Wynn et al., 2013; DeFalco et al., 2014). In adult animals, macrophages are derived from circulating monocytes originating in the bone marrow, but much of the tissue-resident population arise from erythro-myeloid progenitors (EMPs) in the extra-embryonic yolk sac, appearing around the same time as primitive erythroblasts (Schulz et al., 2012; Kierdorf et al., 2013; McGrath et al., 2015; Gomez Perdiguero et al., 2015; Mass et al., 2016). Of particular interest to our group, macrophages have been shown to act as pro-angiogenic regulators during development (Wynn et al., 2013; DeFalco et al., 2014; Hsu et al., 2015), but there is still much to learn about these early cells. The goal of the present study was to isolate and expand progenitors of yolk-sac-derived Embryonic Macrophages (EMs) in vitro to generate a new platform for mechanistic studies of EM differentiation. To accomplish this goal, we isolated pure (>98%) EGFP+ populations by flow cytometry from embryonic day 9.5 (E9.5) Csf1r-EGFP+/tg mice, then evaluated the angiogenic potential of EMs relative to Bone Marrow-Derived Macrophages (BMDMs). We found that EMs expressed more pro-angiogenic and less pro-inflammatory macrophage markers than BMDMs. EMs also promoted more endothelial cell (EC) cord formation in vitro, as compared to BMDMs in a manner that required direct cell-to-cell contact. Importantly, EMs preferentially matured into microglia when co-cultured with mouse Neural Stem/Progenitor Cells (NSPCs). In conclusion, we have established a protocol to isolate and propagate EMs in vitro, have further defined specialized properties of yolk-sac-derived macrophages, and have identified EM-EC and EM-NSPC interactions as key inducers of EC tube formation and microglial cell maturation, respectively.}, } @article {pmid30016429, year = {2018}, author = {Takahashi-Kariyazono, S and Sakai, K and Terai, Y}, title = {Presence-Absence Polymorphisms of Highly Expressed FP Sequences Contribute to Fluorescent Polymorphisms in Acropora digitifera.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1715-1729}, pmid = {30016429}, issn = {1759-6653}, mesh = {Animals ; Anthozoa/*genetics/growth & development ; Evolution, Molecular ; Exons ; Fluorescence ; Gene Dosage ; Gene Expression ; Gene Library ; Luminescent Proteins/*genetics ; Multigene Family ; Phylogeny ; *Polymorphism, Genetic ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; }, abstract = {Despite many hypotheses regarding the roles of fluorescent proteins (FPs), their biological roles and the genetic basis of FP-mediated color polymorphisms in Acropora remain unclear. In this study, we determined the genetic mechanism underlying fluorescent polymorphisms in A. digitifera. Using a high-throughput sequencing approach, we found that FP gene sequences in FP multigene family exhibit presence-absence polymorphism among individuals. A few particular sequences in short-to-middle wavelength emission and middle-to-long wavelength emission clades were highly expressed in adults, and different sequences were highly expressed in larvae. These highly expressed sequences were absent in the genomes of individuals with low total FP gene expression. In adults, presence-absence differences of the highly expressed FP sequences were consistent with measurements of emission spectra of corals, suggesting that presence-absence polymorphisms of these FP sequences contributed to the fluorescent polymorphisms. The functions of recombinant FPs encoded by highly expressed sequences in adult and larval stages were different, suggesting that expression of FP sequences with different functions may depend on the life-stage of A. digitifera. Highly expressed FP sequences exhibited presence-absence polymorphisms in subpopulations of A. digitifera, suggesting that presence-absence status is maintained during the evolution of A. digitifera subpopulations. The difference in FPs between adults and larvae and the polymorphisms of highly expressed FP genes may provide key insight into the biological roles of FPs in corals.}, } @article {pmid30016420, year = {2018}, author = {Widner, B and Fuchsman, CA and Chang, BX and Rocap, G and Mulholland, MR}, title = {Utilization of urea and cyanate in waters overlying and within the eastern tropical north Pacific oxygen deficient zone.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy138}, pmid = {30016420}, issn = {1574-6941}, abstract = {In marine oxygen deficient zones (ODZs), which contribute up to half of marine N loss, microbes use nitrogen (N) for assimilatory and dissimilatory processes. Here, we examine N utilization above and within the ODZ of the Eastern Tropical North Pacific Ocean, focusing on distribution, uptake and genes for the utilization of two simple organic N compounds, urea and cyanate. Ammonium, urea and cyanate concentrations generally peaked in the oxycline while uptake rates were highest in the surface. Within the ODZ, concentrations were lower, but urea N and C and cyanate C were taken up. All identified autotrophs had an N assimilation pathway that did not require external ammonium: ODZ Prochlorococcus possessed genes to assimilate nitrate, nitrite and urea; nitrite oxidizers (Nitrospina) possessed genes to assimilate nitrite, urea and cyanate; anammox bacteria (Scalindua) possessed genes to utilize cyanate; and ammonia-oxidizing Thaumarchaeota possessed genes to utilize urea. Urease genes were present in 20% of microbes, including SAR11, suggesting the urea utilization capacity was widespread. In the ODZ core, cyanate genes were largely (∼95%) associated with Scalindua, suggesting that, within this ODZ, cyanate N is primarily used for N loss via anammox (cyanammox), and that anammox does not require ammonium for N loss.}, } @article {pmid30016235, year = {2018}, author = {Zhang, W and Yuan, Y and Su, D and Ding, L and Yan, X and Wu, M and Epstein, SS and He, S}, title = {Saccharospirillum mangrovi sp. nov., a bacterium isolated from mangrove sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2813-2818}, doi = {10.1099/ijsem.0.002899}, pmid = {30016235}, issn = {1466-5034}, mesh = {Avicennia ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative, spirilla, non-spore-forming, motile and strictly aerobic bacterium, designated HK-33T, was isolated from a mangrove sediment sample in Haikou city, Hainan Province, China. Strain HK-33T was able to grow at 10-45 °C (optimum 37 °C), 0.5-12.0 % (w/v) NaCl (2.0 %, w/v) and pH 5.5-8.5 (pH 7.0). The major cellular fatty acids were C16 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). Ubiquinone-8 was the predominant respiratory quinone, and Q-9 was present in trace amounts. The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, two unidentified phospholipids, two unidentified glycolipids, an unidentified aminophosphoglycolipid and two unidentified lipids. The DNA G+C content was 57.3 mol%. According to 16S rRNA gene sequences similarity, strain HK-33T shared 98.6 %, 96.4%, 95.7 and 94.9 % sequence similarities to the species Saccharospirillum correiae CPA1T, Saccharospirillum impatiens EL-105T, Saccharospirillum salsuginis YIM-Y25T and Saccharospirillum aestuarii IMCC 4453T, respectively. Phylogenetic analysis showed that strain HK-33T was clustered with S. correiae CPA1T, S. impatiens EL-105T, S. salsuginis YIM-Y25T and S. aestuarii IMCC 4453T. Results of DNA-DNA hybridization analysis revealed that strain HK-33T shared 36.3±1.7 % DNA relatedness with S. correiae CPA1T. On the basis of its phenotypic, chemotaxonomic and genotypic characteristics, strain HK-33T is considered to represent a novel species in the genus Saccharospirillum, for which the name Saccharospirillummangrovi sp. nov. is proposed. The type strain is HK-33T (=KCTC 62178T=MCCC 1K03440T).}, } @article {pmid30016234, year = {2018}, author = {Diéguez, AL and Pérez-Cataluña, A and Figueras, MJ and Romalde, JL}, title = {Arcobacter haliotis Tanaka et al. 2017 is a later heterotypic synonym of Arcobacter lekithochrous Diéguez et al. 2017.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2851-2854}, doi = {10.1099/ijsem.0.002909}, pmid = {30016234}, issn = {1466-5034}, mesh = {Animals ; Arcobacter/*classification/genetics ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Gastropoda/microbiology ; Genes, Bacterial ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The draft whole-genome sequence of Arcobacter haliotis strain LMG 28652T was obtained and compared against the type strain of Arcobacter lekithochrous LFT 1.7T. High similarity was found between the two strains, showing average nucleotide identity and in silico DNA-DNA hybridization values of 98.40 and 86.10 %, respectively. These values indicated that both genomes belonged to the same species, confirming the evidences derived from the phylogenetic analysis performed with the 16S rRNA gene and the concatenated sequences of five housekeeping genes. In addition, the metabolic, physiological and chemotaxonomic features of A. haliotis LMG 28652T were shown to be congruent with those of A. lekithochrous. We conclude that Arcobacter haliotis Tanaka et al. 2017 is a later heterotypic synonym of Arcobacter lekithochrousDiéguez et al. 2017.}, } @article {pmid30016233, year = {2018}, author = {Lee, Y and Lee, B and Lee, K and Jeon, CO}, title = {Solimonas fluminis sp. nov., isolated from a freshwater river.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2755-2759}, doi = {10.1099/ijsem.0.002865}, pmid = {30016233}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A strictly aerobic, catalase-negative and oxidase-positive bacterium (HR-BBT), isolated from a water sample of the Han River, was taxonomically studied using a polyphasic approach. Cells were Gram-stain-negative motile rods with a polar flagellum. The strain grew at 20-35 °C and pH 7-8 and in the absence of NaCl. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HR-BBT belonged to the family Nevskiaceae in the phylum Proteobacteria and formed a phylogenic lineage with members of the genus Solimonas. A comparison of the 16S rRNA gene sequences of strain HR-BBT and the type strains of closely related species of the genus Solimonas showed that it shared highest sequence similarity with Solimonas terrae KIS83-12T (94.9 %), Solimonas soli DCY12T (94.8 %), Solimonas variicoloris MN28T (94.4 %) and Solimonas flava CW-KD 4T (94.2 %). The fatty acids of the strain consisted of summed features 8 (comprising C18 : 1ω6c and/or C18 : 1ω7c) and 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c), C16 : 0 and C12 : 0 as major components. The polar lipids comprised phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, three unidentified phospholipids and an unidentified lipid. Ubiquinone-8 was detected as the sole respiratory quinone. The DNA G+C content of strain HR-BBT was 68.5 mol%. Based on the genotypic, chemotaxonomic and phenotypic analyses, strain HR-BBT represents a novel species of the genus Solimonas, for which the name Solimonas fluminis sp. nov. is proposed. The type strain is HR-BBT (=KACC 19410T=JCM 32268T).}, } @article {pmid30016230, year = {2018}, author = {Lee, Y and Jeon, CO}, title = {Solitalea longa sp. nov., isolated from freshwater and emended description of the genus Solitalea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2826-2831}, doi = {10.1099/ijsem.0.002903}, pmid = {30016230}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-negative, strictly aerobic, oxidase-positive, catalase-negative and yellow-pigmented bacterium, designated strain HR-AVT, was isolated from a water sample of the Han River. Cells were elongated rods with gliding motility without flagellum. Growth was observed at 5-30 °C (optimum, 20 °C), pH 7-8 and 0-0.5 % NaCl. The major respiratory quinone was menaquinone-7. The major fatty acids were iso-C15 : 0, summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c) and anteiso-C15 : 0. The polar lipids comprised phosphatidylethanolamine, an unidentified amino lipid and five unidentified lipids. The DNA G+C content of strain HR-AVT was 38.4 mol%. Results of phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HR-AVTbelonged to the family Sphingobacteriaceae in the phylum Bacteroidetes and formed a phylogenic lineage with Solitalea canadensis DSM 3403T and Solitalea koreensis R2A36-4T. Strain HR-AVT was most closely related to S. canadensis DSM 3403T and S. koreensis R2A36-4T with 97.3 and 94.0 % 16S rRNA gene sequence similarities, respectively, and then had low similarities (below 90.9 %) with other bacteria with validly published names. Average nucleotide identity and in silico DNA-DNA hybridization values between strain HR-AVT and S. canadensis were 74.0 and 19.7 %, respectively. Based on these results, strain HR-AVT represents a novel species of the genus Solitalea, for which the name Solitalea longa sp. nov. is proposed. The type strain is HR-AVT (=KACC 19411T=JCM 32259T). An emended description of the genus Solitalea is also proposed.}, } @article {pmid30016229, year = {2018}, author = {Zhao, Z and Shen, X and Chen, W and Yu, XY and Fu, GY and Sun, C and Wu, M}, title = {Emcibacter congregatus sp. nov., isolated from sediment cultured in situ.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2846-2850}, doi = {10.1099/ijsem.0.002906}, pmid = {30016229}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative, aerobic, motile, rod-shaped, pale-yellow bacterial strain, designated as ZYLT, isolated from a cultured in situ sediment sample collected from the East China Sea coast, was studied using a polyphasic taxonomic approach. Strain ZYLT grew at 4-30 °C (optimum, 25 °C), at pH 6.0-8.5 (pH 7.0) and with 0-7.0 % (w/v) NaCl (2.0 %). Results of phylogenetic analysis based on 16S rRNA gene sequences clearly showed that strain ZYLT and Emcibacter nanhaiensis HTCJW17T, which was most closely related to strain ZYLT with 93.6 % sequence similarity, clustered together. The genomic DNA G+C content was 51.5 % (genome sequence). The quinone system was composed only of ubiquinone-10. Strain ZYLT possessed C18 : 1ω7c and/or C18 : 1ω6c (summed feature 8), iso-C15 : 0 2-OH and/or C16 : 1ω7c (summed feature 3), C14 : 0 2-OH and C14 : 0 as the major fatty acids. The content of summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1ω7c) in strain ZYLT was far greater than that in E. nanhaiensis. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminophospholipids, three unidentified phospholipids, one unidentified aminolipid and four unidentified lipids. One unidentified aminophospholipid and two unidentified lipids present in strain ZYLT were not found in E. nanhaiensis in this research. On the basis of phenotypic, phylogenetic and chemotaxonomic data, strain ZYLT (=KCTC 62328T=JCM 32378T=MCCC 1K03526T) represents a novel species of the genus Emcibacter for which the name Emcibacter congregatus sp. nov. is proposed.}, } @article {pmid30016228, year = {2018}, author = {Kudryashova, EB and Karlyshev, AV and Ariskina, EV and Streshinskaya, GM and Vinokurova, NG and Kopitsyn, DS and Evtushenko, LI}, title = {Cohnella kolymensis sp. nov., a novel bacillus isolated from Siberian permafrost.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2912-2917}, doi = {10.1099/ijsem.0.002919}, pmid = {30016228}, issn = {1466-5034}, mesh = {Bacillales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Peptidoglycan/chemistry ; Permafrost/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Siberia ; *Soil Microbiology ; Vitamin K 2/chemistry ; }, abstract = {A facultative anaerobic, rod-shaped, endospore-forming and non-motile bacterium was isolated from permafrost sediment cores in the Kolyma lowland, Siberia, Russia. The permafrost isolate clustered with members of the genus Cohnella on the basis of 16S rRNA gene sequence analysis and showed the highest sequence similarity to Cohnella saccharovorans CJ22T (96.3 %), followed by Cohnella cellulosilytica FCN3-3T (96.0 %) and Cohnella panacarvi KCTC 13060T (96.0 %). The chemotaxonomic characteristics (quinone system, cellular fatty acids and polar lipid profile) of strain 20.16T were consistent with members of the genus Cohnella. The peptidoglycan diaminoacids included meso-diaminopimelic acid and a small amount of ll-diaminopimelic acid. The molar ratio and composition of major amino acids (meso-diaminopimelic acid, alanine, and glutamic acid) correspond to the peptydoglycan type A1γ. The estimated genome size of strain 20.16T is 4.34 Mb (lower than those in other Cohnella species). The genome has a G+C content of 50.5 mol% and encodes 4843 predicted genes, of these 4740 are protein-coding ones. The results of chemotaxonomic, physiological and biochemical characterization allowed clear differentiation of strain 20.16T from the closest Cohnella species. Based on data provided, a new species Cohnella kolymensis sp. nov. is proposed, with 20.16T (=VKM B-2846T=DSM 104983T) as the type strain.}, } @article {pmid30016227, year = {2018}, author = {Wong, SK and Yoshizawa, S and Nakajima, Y and Cuadra, MJ and Nogi, Y and Nakamura, K and Takami, H and Ogura, Y and Hayashi, T and Chiura, HX and Hamasaki, K}, title = {Amylibacter kogurei sp. nov., a novel marine alphaproteobacterium isolated from the coastal sea surface microlayer of a marine inlet.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2872-2877}, doi = {10.1099/ijsem.0.002911}, pmid = {30016227}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Bays ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Japan ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-negative bacterium, designated 4G11T, was isolated from the sea surface microlayer of a marine inlet. On the basis of 16S rRNA gene sequence analysis, the strain showed the closest similarity to Amylibacter ulvae KCTC 32465T (99.0 %). However, DNA-DNA hybridization values showed low DNA relatedness between strain 4G11T and its close phylogenetic neighbours, Amylibacter marinus NBRC 110140T (8.0±0.4 %) and Amylibacter ulvae KCTC 32465T (52.9±0.9 %). Strain 4G11T had C18 : 1, C16 : 0 and C18 : 2 as the major fatty acids. The only isoprenoid quinone detected for strain 4G11T was ubiquinone-10. The major polar lipids were phosphatidylglycerol, phosphatidylcholine, one unidentified polar lipid, one unidentified phospholipid and one unidentified aminolipid. The DNA G+C content of strain 4G11T was 50.0 mol%. Based on phenotypic and chemotaxonomic characteristics and analysis of the 16S rRNA gene sequence, the novel strain should be assigned to a novel species, for which the name Amylibacter kogurei sp. nov. is proposed. The type strain of Amylibacter kogurei is 4G11T (KY463497=KCTC 52506T=NBRC 112428T).}, } @article {pmid30016224, year = {2018}, author = {Kim, SJ and Ahn, JH and Heo, J and Cho, H and Weon, HY and Hong, SB and Kim, JS and Kwon, SW}, title = {Phreatobacter cathodiphilus sp. nov., isolated from a cathode of a microbial fuel cell.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2855-2859}, doi = {10.1099/ijsem.0.002904}, pmid = {30016224}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; *Bioelectric Energy Sources ; DNA, Bacterial/genetics ; Electrodes/*microbiology ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel bacterial strain, S-12T, of a member of the genus Phreatobacterwas isolated from a cathode of a microbial fuel cell from Suwon City, South Korea. Cells were Gram-staining-negative, aerobic, non-sporulating rods, motile by means of a polar flagellum, and formed white round colonies. The strain grew at the range of 10-40 °C (optimum, 28-30 °C), pH 6.0-10.0 (optimum 7.0-8.0) and 0-1 % NaCl. The 16S rRNA gene sequence analysis showed the relatedness of S-12T to Phreatobacter stygiusYC6-17T (98.2 %) and Phreatobacter oligotrophusPI_21T (98.1 %). The major respiratory quinone was ubiquinone Q-10. Polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine and an unidentified lipid. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The DNA G+C content was 69.3 mol%. On the basis of its differences from species of the genus Phreatobacter with validly published names, strain S-12T is identified as representing a novel species, for which the proposed name is Phreatobactercathodiphilus sp. nov., with S-12T as the type strain (=KACC 18497T=JCM 31612T).}, } @article {pmid30016171, year = {2018}, author = {Mokkonen, M and Koskela, E and Procyshyn, T and Crespi, B}, title = {Socio-reproductive Conflicts and the Father's Curse Dilemma.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {250-262}, doi = {10.1086/698216}, pmid = {30016171}, issn = {1537-5323}, abstract = {Evolutionary conflicts between males and females can manifest over sexually antagonistic interactions at loci or over sexually antagonistic interests within a locus. The latter form of conflict, intralocus sexual conflict, arises from sexually antagonistic selection and constrains the fitness of individuals through a phenotypic compromise. These conflicts, and socio-reproductive interactions in general, are commonly mediated by hormones, and thus predictive insights can be gained from studying their mediating effects. Here, we integrate several lines of evidence to describe a novel, hormonally mediated reproductive dilemma that we call the father's curse, which results from an intralocus conflict between mating and parental efforts. Essentially, a genetic locus exerts pleiotropic and antagonistic effects on the mating effort of one individual and the parental effort of a related individual who is the primary provider of parental care. We outline the criteria for operation of the father's curse dilemma, provide evidence of the phenomenon, and discuss the predictions and outcomes arising from its dynamics. By integrating the effects of hormones into socio-reproductive conflicts and socio-reproductive effort, clearer links between genotypes, phenotypes, and fitness can be established.}, } @article {pmid30016170, year = {2018}, author = {Biro, PA and Garland, T and Beckmann, C and Ujvari, B and Thomas, F and Post, JR}, title = {Metabolic Scope as a Proximate Constraint on Individual Behavioral Variation: Effects on Personality, Plasticity, and Predictability.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {142-154}, doi = {10.1086/697963}, pmid = {30016170}, issn = {1537-5323}, abstract = {Behavioral ecologists have hypothesized that among-individual differences in resting metabolic rate (RMR) may predict consistent individual differences in mean values for costly behaviors or for behaviors that affect energy intake rate. This hypothesis has empirical support and presently attracts considerable attention, but, notably, it does not provide predictions for individual differences in (a) behavioral plasticity or (b) unexplained variation (residual variation from mean individual behavior, here termed predictability). We outline how consideration of aerobic maximum metabolic rate (MMR) and particularly aerobic scope (= MMR - RMR) can be used to simultaneously make predictions about mean and among- and within-individual variation in behavior. We predict that while RMR should be proportional to an individual's mean level of sustained behavioral activity (one aspect of its personality), individuals with greater aerobic scope will also have greater scope to express behavioral plasticity and/or greater unpredictability in behavior (=greater residual variation). As a first step toward testing these predictions, we analyze existing activity data from selectively bred lines of mice that differ in both daily activity and aerobic scope. We find that replicate high-scope mice are more active on average and show greater among-individual variation in activity, greater among-individual variation in plasticity, and greater unpredictability. These data provide some tentative first support for our hypothesis, suggesting that further research on this topic would be valuable.}, } @article {pmid30016169, year = {2018}, author = {Bateman, AW and Ozgul, A and Krkošek, M and Clutton-Brock, TH}, title = {Matrix Models of Hierarchical Demography: Linking Group- and Population-Level Dynamics in Cooperative Breeders.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {188-203}, doi = {10.1086/698217}, pmid = {30016169}, issn = {1537-5323}, abstract = {For highly social species, population dynamics depend on hierarchical demography that links local processes, group dynamics, and population growth. Here, we describe a stage-structured matrix model of hierarchical demography, which provides a framework for understanding social influences on population change. Our approach accounts for dispersal and affords insight into population dynamics at multiple scales. The method has close parallels to integral projection models but focuses on a discrete characteristic (group size). Using detailed long-term records for meerkats (Suricata suricatta), we apply our model to explore patterns of local density dependence and implications of group size for group and population growth. Taking into account dispersers, the model predicts a per capita growth rate for social groups that declines with group size. It predicts that larger social groups should produce a greater number of new breeding groups; thus, dominant breeding females (responsible for most reproduction) are likely to be more productive in larger groups. Considering the potential for future population growth, larger groups have the highest reproductive value, but per capita reproductive value is maximized for individuals in smaller groups. Across a plausible range of dispersal conditions, meerkats' long-run population growth rate is maximized when individuals form groups of intermediate size.}, } @article {pmid30016168, year = {2018}, author = {Näpflin, K and Schmid-Hempel, P}, title = {High Gut Microbiota Diversity Provides Lower Resistance against Infection by an Intestinal Parasite in Bumblebees.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {131-141}, doi = {10.1086/698013}, pmid = {30016168}, issn = {1537-5323}, abstract = {The microbiome, especially the gut flora, is known to affect the interaction between parasites and their hosts. In this context, a parasitic infection can be viewed as an invasion into the preexisting microbial ecological community. Hence, in addition to the intrinsic defense mechanisms of the host itself, infection success depends on the colonization resistance of the microbiota. In the bumblebee Bombus terrestris, the microbiota provides resistance to the intestinal parasite Crithidia bombi, yet which properties actually provide protection remains largely unknown. Here, we show that the community structure of the gut microbiota-in terms of bacterial operational taxonomic units (OTUs) of 16S ribosomal RNA gene sequences-before parasite exposure can be informative of the eventual infection outcome. Specifically, higher microbiota OTU diversity is associated with less resistance. However, the microbial community structure does not differ between infected and noninfected individuals or between infected individuals of varying susceptibility. This suggests that parasite infection success depends on the microbiota composition but that subsequent changes occur, although the exact alteration that occurs remains elusive. In fact, the bumblebee microbiota is surprisingly unaffected by parasite exposure and infection. Rather, the microbiota-host interaction before parasite exposure seems to be a key mechanism regulating resistance to infection.}, } @article {pmid30016167, year = {2018}, author = {Chapman, T}, title = {Sexual Conflict: Mechanisms and Emerging Themes in Resistance Biology.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {217-229}, doi = {10.1086/698169}, pmid = {30016167}, issn = {1537-5323}, support = {BB/L003139/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/H008047/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Sexual conflict is acknowledged as pervasive, with the potential to generate and maintain genetic variation. Mechanistic studies of conflict have been important in providing direct evidence for the existence of sexual conflict. They have also led to the growing realization that there is a striking phenotypic diversity of adaptations whose evolution can be shaped by sexually antagonistic selection. The mechanisms involved range from the use of genital spines, claspers, songs, and smells to ejaculate molecules. In one well-studied example, sexual conflict can occur over the sexually antagonistic effects of seminal fluid proteins in Drosophila melanogaster. However, an important puzzle remains, namely, why seminal fluid proteins are so numerous and complex, hence whether all or some are involved in mediating sexual conflict. I hypothesize that this rich diversity and the complexity of traits subject to sexually antagonistic selection in general may arise, at least in part, due to the deployment of sexually antagonistic adaptations in males in a way that lessens the probability of broadscale, strong resistance evolution in females. In elaborating this hypothesis, I explore how research into the evolution of resistance to insecticides, antimicrobials, and vaccines might be used to provide insights into the evolution of female resistance to the effects of sexually antagonistic manipulative traits of males. In this manner, the manipulative traits of males can be resistance-proofed.}, } @article {pmid30016166, year = {2018}, author = {Sanín, C and Anderson, RP}, title = {A Framework for Simultaneous Tests of Abiotic, Biotic, and Historical Drivers of Species Distributions: Empirical Tests for North American Wood Warblers Based on Climate and Pollen.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {E48-E61}, doi = {10.1086/697537}, pmid = {30016166}, issn = {1537-5323}, abstract = {Understanding how abiotic, biotic, and historical factors shape species distributions remains a central question in ecology, but studies linking biotic factors to continental-scale patterns remain scarce. Here, we present a novel framework for simultaneously testing patterns expected when abiotic, biotic, or historical factors drive species range limits. We use ecological niche models to produce empirical estimates of the "biotic, abiotic, and movement" paradigm (BAM diagrams), which previously has been used only theoretically. On the basis of climatic and pollen data as well as explicit consideration of dispersal limitations, we implement the framework for a group of North American birds (Oreothlypis warblers) with clear habitat associations. Because the pollen-based predictor variables characterize vegetation, they represent biotic factors needed by each bird species. Although continental-scale patterns of distribution are traditionally attributed to abiotic factors, only one species matched the hypothesis of solely abiotic drivers. In contrast, pollen-based models indicate biotic drivers for two species, correctly predicting their absence in climatically suitable areas. These results highlight the feasibility of considering and quantifying the potential effects of biotic interactions on species ranges, especially when interactions can be decoupled from abiotic factors. Furthermore, the availability of pollen data now and in the Holocene highlights the potential of these data to be used to predict range shifts of other organisms tightly dependent on particular vegetation types.}, } @article {pmid30016165, year = {2018}, author = {Gerber, N and Booksmythe, I and Kokko, H}, title = {Sex Allocation Theory for Facultatively Sexual Organisms Inhabiting Seasonal Environments: The Importance of Bet Hedging.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {155-170}, doi = {10.1086/697727}, pmid = {30016165}, issn = {1537-5323}, abstract = {Adaptive explanations for dormancy often invoke bet hedging, where reduced mean fitness can be adaptive if it associates with reduced fitness variance. Sex allocation theory typically ignores variance effects and focuses on mean fitness. For many cyclical parthenogens, these themes become linked, as only sexually produced eggs undergo the dormancy needed to survive harsh conditions. We ask how sex allocation and the timing of sex evolve when this constraint exists in the form of a trade-off between asexual reproduction and sexual production of dormant eggs-the former being crucial for within-season success and the latter for survival across seasons. We show that male production can be temporally separated from or co-occur with sex, depending on whether direct (time) or indirect (population density) cues of the season's end are available and whether population growth is density dependent. Sex generally occurs late in the season but is induced earlier in unpredictable environments. When only indirect cues are available, the temporal spread of sex, and with it the production of dormant stages, is even larger and, given sufficient mortality, leads to endogenous population cycles in which frequent sex coincides with high densities. In all scenarios, algorithms maximizing geometric mean fitness have reduced fitness variance compared with a hypothetical non-bet hedger, confirming that the timing of male production and sex in facultative seasonal settings can be bet-hedging traits.}, } @article {pmid30016164, year = {2018}, author = {Song, MJ and Schaack, S}, title = {Evolutionary Conflict between Mobile DNA and Host Genomes.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {263-273}, doi = {10.1086/698482}, pmid = {30016164}, issn = {1537-5323}, abstract = {The proportion of eukaryotic genomes composed of active or formerly active mobile elements (MEs) is known to vary widely across lineages, but the explanations for why remain largely unknown. Given that ME activity, like other forms of mutation, is thought to be (on average) slightly deleterious in terms of phenotypic effects, understanding the widespread proliferation of MEs in host genomes requires an evolutionary framework. To better develop such a framework, we review the spectrum of resolutions to the genetic conflict between MEs and their hosts: inactivation of MEs due to mutation accumulation, negative selection (or lack thereof) against hosts with high ME loads, silencing of MEs (by hosts or MEs), ME domestication by their hosts, and the horizontal transfer of MEs to new hosts. We also highlight ecological and evolutionary theory from which ME researchers might borrow in order to explain large-scale patterns of ME dynamics across systems. We hope that a synthesis of the surprisingly significant role played by MEs in the genome, as well as the spectrum of resolutions, applicable theory, and recent discoveries, will have two outcomes for future researchers: better parsing of known variation in ME proliferation patterns across genomes and the development of testable models and predictions regarding the evolutionary trajectory of MEs based on a combination of theory, the comparative method, experimental evolution, and empirical observations.}, } @article {pmid30016163, year = {2018}, author = {San-Jose, LM and Roulin, A}, title = {Toward Understanding the Repeated Occurrence of Associations between Melanin-Based Coloration and Multiple Phenotypes.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {111-130}, doi = {10.1086/698010}, pmid = {30016163}, issn = {1537-5323}, abstract = {Melanin is the most widespread pigment in organisms. Melanin-based coloration has been repeatedly observed to be associated with the same traits and in the same direction in different vertebrate and insect species. However, whether any factors that are common to different taxa account for the repeated evolution of melanin-phenotype associations remains unclear. We propose to approach this question from the perspective of convergent and parallel evolution to clarify to what extent different species have evolved the same associations owing to a shared genetic basis and being subjected to similar selective pressures. Our current understanding of the genetic basis of melanin-phenotype associations allows for both convergent and parallel evolution, but this understanding is still limited. Further research is needed to clarify the generality and interdependencies of the different proposed mechanisms (supergenes, pleiotropy based on hormones, or neural crest cells). The general ecological scenarios whereby melanin-based coloration is under selection-protection from ultraviolet radiation, thermoregulation in cold environments, or as a signal of social status-offer a good opportunity to study how melanin-phenotype associations evolve. Reviewing these scenarios shows that some traits associated with melanin-based coloration might be selected together with coloration by also favoring adaptation but that other associated traits might impede adaptation, which may be indicative of genetic constraints. We therefore encourage further research on the relative roles that selection and genetic constraints play in shaping multiple melanin-phenotype associations. Placed into a phylogenetic context, this will help clarify to what extent these associations result from convergent or parallel evolutionary processes and why melanin-phenotype associations are so common across the tree of life.}, } @article {pmid30016162, year = {2018}, author = {Dedrick, AG and Baskett, ML}, title = {Integrating Genetic and Demographic Effects of Connectivity on Population Stability: The Case of Hatchery Trucking in Salmon.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {E62-E80}, doi = {10.1086/697581}, pmid = {30016162}, issn = {1537-5323}, abstract = {Connectivity among populations can have counteracting effects on population stability. Demographically, connectivity can rescue local populations but increase the synchrony across populations. Genetically, connectivity can counteract drift locally but homogenize genotypes across populations. Population independence and diversity underlies system-level buffering against environmental variability, termed the portfolio effect. The portfolio effect has declined in California fall-run Chinook salmon, possibly in part because of the trucking of juvenile hatchery-reared fish for downstream release, which reduces juvenile mortality but increases the connectivity between rivers. We use a dynamical population model to test whether this increased connectivity can explain the loss of the portfolio effect and quantify the relative demographic and genetic contributions to portfolio effect erosion. In the model, populations experience different within-population environmental conditions and the same time-variable ocean conditions, the response to which can depend on a quantitative genetic trait. We find that increased trucking for one population's hatchery can lead to a loss of the portfolio effect, with a system-level trade-off between increased average abundance and increased variability in abundance. This trade-off is much stronger when we include the effects of genetic homogenization than when we consider demographic synchronization alone. Therefore, genetic homogenization can outweigh demographic synchrony in determining the system-level effect of connectivity.}, } @article {pmid30016161, year = {2018}, author = {Folk, RA and Visger, CJ and Soltis, PS and Soltis, DE and Guralnick, RP}, title = {Geographic Range Dynamics Drove Ancient Hybridization in a Lineage of Angiosperms.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {171-187}, doi = {10.1086/698120}, pmid = {30016161}, issn = {1537-5323}, abstract = {Elucidating the dynamic distribution of organismal lineages has been central to biology since the nineteenth century, yet the difficulty of combining biogeographic methods with shifts in habitat suitability remains a limitation. This integration, however, is critical to understanding geographic distributions, present and past, as well as the time-extended trajectories of lineages. Here, we link previous advances in phyloclimatic modeling to develop a framework that overcomes existing methodological gaps by predicting potential ecological and geographic overlap directly from estimated ancestral trait distributions. We show the utility of this framework by focusing on a clade in the montane angiosperm genus Heuchera, which is noteworthy in that it experienced ancient introgression from circumboreally distributed species of Mitella, lineages now ~1,300 km disjunct. Using this system, we demonstrate an application of ancestral state reconstruction to assess geographic range dynamics in a lineage lacking a fossil record. We test hypotheses regarding inferred past geographic distributions and examine the potential for ancient geographic contact. Application of this multifaceted approach suggests potential past contact between species of Heuchera and Mitella in western North America during cooler periods of the Pleistocene. Integration of niche models and phylogenetic estimates suggests that climatic cooling may have promoted range contact and gene flow between currently highly disjunct species. Our approach has wide applicability for testing hypotheses concerning organismal co-occurrences in deep time.}, } @article {pmid30016160, year = {2018}, author = {Immler, S and Otto, SP}, title = {The Evolutionary Consequences of Selection at the Haploid Gametic Stage.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {241-249}, doi = {10.1086/698483}, pmid = {30016160}, issn = {1537-5323}, abstract = {As an immediate consequence of sexual reproduction, biphasic life cycles with alternating diploid and haploid phases are a common characteristic of sexually reproducing eukaryotes. Much of our focus in evolutionary biology has been directed toward dynamics in diploid or haploid populations, but we rarely consider selection occurring during both phases when studying evolutionary processes. One of the reasons for this apparent omission is the fact that many flowering plants and metazoans are predominantly diploid with a very short haploid gametic phase. While this gametic phase may be short, it can play a crucial role in fundamental processes including the rate of adaptation, the load of mutation, and the evolution of features such as recombination. In addition, if selection acts in different directions between the two phases, a genetic conflict will occur, impacting the maintenance of genetic variation. Here we provide an overview of theoretical and empirical studies investigating the importance of selection at the haploid gametic phase in predominantly diploid organisms and discuss future directions to improve our understanding of the underlying dynamics and the general implications of haploid selection.}, } @article {pmid30016159, year = {2018}, author = {Benadi, G and Gegear, RJ}, title = {Adaptive Foraging of Pollinators Can Promote Pollination of a Rare Plant Species.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {E81-E92}, doi = {10.1086/697582}, pmid = {30016159}, issn = {1537-5323}, abstract = {Most pollinators have the foraging flexibility to visit a wide variety of plant species. Yet few studies of pollinator-mediated processes in plants have considered the effects of variation in individual foraging patterns on plant reproductive success. In this study, we use an individual-based model of pollinator foraging economics to predict how visitation rates and pollination success of two coflowering plant species change with their frequency (relative abundance). Whereas previous studies suggested that adaptive foraging of pollinators always favors pollination of abundant plant species (positive frequency dependence), here we show that under certain conditions the per capita pollination success of a rare plant species can exceed that of a more abundant species. Specifically, when the overall flower density is sufficiently high and pollinators' perception ranges are sufficiently large, animals with limited memory of previously encountered rewards forage in a way that favors pollination of the rarer plant species. Moreover, even with perfectly informed foragers, a rare plant species benefits more from offering a higher floral reward than a more abundant species. Our results show that adaptive foraging of individual pollinators can have important implications for plant community dynamics and the persistence of rare plant species.}, } @article {pmid30016158, year = {2018}, author = {Rowe, L and Chenoweth, SF and Agrawal, AF}, title = {The Genomics of Sexual Conflict.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {274-286}, doi = {10.1086/698198}, pmid = {30016158}, issn = {1537-5323}, abstract = {Sexual dimorphism is a substantial contributor to the diversity observed in nature, extending from elaborate traits to the expression level of individual genes. Sexual conflict and sexually antagonistic coevolution are thought to be central forces driving the dimorphism of the sexes and its diversity. We have substantial data to support this at the phenotypic level but much less at the genetic level, where distinguishing the role of conflict from other forms of sex-biased selection and from other processes is challenging. Here we discuss the powerful effects sexual conflict may have on genome evolution and critically evaluate the supporting evidence. Although there is much potential for sexual conflict to affect genome evolution, we have relatively little compelling evidence of a genomic signature of sexual conflict. A central obstacle is the mismatch between taxa in which we understand sexually antagonistic selection and those in which we understand genetics.}, } @article {pmid30016157, year = {2018}, author = {Adler, FR and Quinonez, S and Plowes, N and Adams, ES}, title = {Mechanistic Models of Conflict between Ant Colonies and Their Consequences for Territory Scaling.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {204-216}, doi = {10.1086/698121}, pmid = {30016157}, issn = {1537-5323}, abstract = {Territory size in social insects depends on the rules by which border conflicts are resolved. We present three mechanistic mathematical models of conflict, inspired by the behavior of the pavement ant Tetramorium immigrans, to predict the advantage of larger colonies in pairwise contests and the resulting scaling of territory size with worker force. The models track the number of ants in the nest traveling to and from the boundary or engaged at the boundary. Ants at the boundary base their recruitment response on the relative numbers of ants from the two colonies. With two colonies, our central result is that the larger colony gains a territory disproportionately larger than the ratio of worker forces would indicate. This disproportionate territory control determines the scaling relation of territory size with worker force in a population. In two dimensions, if territory size were proportional to worker force, the slope of the scaling relation between log territory size and log worker force would be 1.0. With disproportionate territories, this slope is larger and can be explicitly approximated in terms of model parameters, and it is steepest when colonies are packed close to each other, when ants run quickly, or when colonies are small. A steeper slope exaggerates the advantage of larger colonies, creating a positive feedback that could amplify the inequality of the worker force distribution.}, } @article {pmid30016156, year = {2018}, author = {Day, T and McLeod, DV}, title = {The Role of Phenotypic Plasticity in Moderating Evolutionary Conflict.}, journal = {The American naturalist}, volume = {192}, number = {2}, pages = {230-240}, doi = {10.1086/698170}, pmid = {30016156}, issn = {1537-5323}, abstract = {Evolutionary conflicts arise when the fitness interests of interacting individuals differ. Well-known examples include sexual conflict between males and females and antagonistic coevolution between hosts and parasites. A common feature of such conflicts is that compensating evolutionary change in each of the parties can lead to little overt change in the interaction itself. As a result, evolutionary conflict is expected to persist even if the evolutionary dynamic between the parties reaches an equilibrium. In these cases, it is of interest to know whether certain kinds of interactions are expected to lead to greater or lesser evolutionary conflict at such evolutionary stalemates. Here we present a theoretical analysis showing that when one of the interacting parties can respond to the other through adaptive phenotypic plasticity, evolutionary conflict is reduced. Paradoxically, however, it is the party that does not express adaptive plasticity that experiences less conflict. Conflict for the party displaying adaptive plasticity can increase or decrease, depending on the situation.}, } @article {pmid30015414, year = {2018}, author = {Blanco, MB and Dausmann, KH and Faherty, SL and Yoder, AD}, title = {Tropical heterothermy is "cool": The expression of daily torpor and hibernation in primates.}, journal = {Evolutionary anthropology}, volume = {27}, number = {4}, pages = {147-161}, doi = {10.1002/evan.21588}, pmid = {30015414}, issn = {1520-6505}, mesh = {Africa ; Animals ; Asia ; Female ; Hibernation/*physiology ; Lemur/*physiology ; Lorisidae/*physiology ; Madagascar ; Male ; Torpor/physiology ; }, abstract = {Living nonhuman primates generally inhabit tropical forests, and torpor is regarded as a strategy employed by cold-adapted organisms. Yet, some primates employ daily torpor or hibernation (heterothermy) under obligatory, temporary, or emergency circumstances. Though heterothermy is present in most mammalian lineages, there are only three extant heterothermic primate lineages: bushbabies from Africa, lorises from Asia, and dwarf and mouse lemurs from Madagascar. Here, we analyze their phenotypes in the general context of tropical mammalian heterothermy. We focus on Malagasy lemurs as they have been the most intensively studied and also show an unmatched range of flexibility in their heterothermic responses. We discuss the evidence for whether heterothermy should be considered an ancestral or derived condition in primates. This consideration is particularly intriguing given that an understanding of the underlying mechanisms for hibernation in lemurs opens the possibility for insight into genotype-phenotype interactions, including those with biomedical relevance for humans.}, } @article {pmid30015353, year = {2018}, author = {Støstad, HN and Johnsen, A and Lifjeld, JT and Rowe, M}, title = {Sperm head morphology is associated with sperm swimming speed: A comparative study of songbirds using electron microscopy.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1918-1932}, doi = {10.1111/evo.13555}, pmid = {30015353}, issn = {1558-5646}, support = {230434/F20//Research Council of Norway/ ; }, abstract = {Sperm exhibit extraordinary levels of morphological diversification across the animal kingdom. In songbirds, sperm have a helically shaped head incorporating a distinct acrosomal membrane or "helical keel," the form and extent of which varies across species. The functional significance of this helical shape, however, remains unknown. Using scanning electron microscopy, we quantified inter- and intraspecific variation in sperm head morphology across 36 songbird species (Passeriformes: Passerida). Using phylogenetic comparative methods, we investigated the relationship between sperm head morphology and both sperm swimming speed and the frequency of extra-pair young (EPY). We found that species whose sperm had a relatively more pronounced helical form (i.e., long acrosome, short nucleus, wide helical membrane, and a more pronounced waveform along the sperm head "core") had faster-swimming sperm. We found no evidence of a relationship between interspecific variation in sperm head morphology and EPY, although we did find that among- and within-male variation in sperm head traits were negatively correlated with EPY. Applying principles of fluid mechanics, we discuss how the helical form of the sperm head may influence swimming speed, and suggest that further studies considering aspects of sperm morphology beyond sperm length are needed to improve our understanding of sperm structure-function relationships.}, } @article {pmid30014616, year = {2018}, author = {Rands, CM and Starikova, EV and Brüssow, H and Kriventseva, EV and Govorun, VM and Zdobnov, EM}, title = {ACI-1 beta-lactamase is widespread across human gut microbiomes in Negativicutes due to transposons harboured by tailed prophages.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14276}, pmid = {30014616}, issn = {1462-2920}, abstract = {Antibiotic resistance is increasing among pathogens, and the human microbiome contains a reservoir of antibiotic resistance genes. Acidaminococcus intestini is the first Negativicute bacterium (Gram-negative Firmicute) shown to be resistant to beta-lactam antibiotics. Resistance is conferred by the aci1 gene, but its evolutionary history and prevalence remain obscure. We discovered that ACI-1 proteins are phylogenetically distinct from beta-lactamases of Gram-positive Firmicutes and that aci1 occurs in bacteria scattered across the Negativicute clade, suggesting lateral gene transfer. In the reference A. intestini RyC-MR95 genome, we found transposons residing within a tailed prophage context are likely vehicles for aci1's mobility. We found aci1 in 56 (4.4%) of 1,267 human gut metagenomes, mostly hosted within A. intestini, and, where could be determined, mostly within a consistent mobile element constellation. These samples are from Europe, China and the USA, showing that aci1 is distributed globally. We found that for most Negativicute assemblies with aci1, the prophage observed in A. instestini is absent, but in all cases aci1 is flanked by varying transposons. The chimeric mobile elements we identify here likely have a complex evolutionary history and potentially provide multiple complementary mechanisms for antibiotic resistance gene transfer both within and between cells.}, } @article {pmid30014579, year = {2018}, author = {von Gunten, K and Hamilton, SM and Zhong, C and Nesbø, C and Li, J and Muehlenbachs, K and Konhauser, KO and Alessi, DS}, title = {Electron donor-driven bacterial and archaeal community patterns along forest ring edges in Ontario, Canada.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {663-672}, doi = {10.1111/1758-2229.12678}, pmid = {30014579}, issn = {1758-2229}, abstract = {Forest rings are 50-1600 m diameter circular structures found in boreal forests around the globe. They are believed to be chemically reducing chimney features, having an accumulation of reduced species in the middle of the ring and oxidation processes occurring at the ring's edges. It has been suggested that microorganisms could be responsible for charge transfer from the inside to the outside of the ring. To explore this, we focused on the changes in bacterial and archaeal communities in the ring edges of two forest rings, the 'Bean' and the 'Thorn North' ring, in proximity to each other in Ontario, Canada. The drier samples from the methane-sourced Bean ring were characterized by the abundance of bacteria from the classes Deltaproteobacteria and Gemmatimonadetes. Geobacter spp. and methanotrophs, such as Candidatus Methylomirabilis and Methylobacter, were highly abundant in these samples. The Thorn North ring, centred on an H2 S accumulation in groundwater, had wetter samples and its communities were dominated by the classes Alphaproteobacteria and Anaerolineae. This ring's microbial communities showed an overall higher microbial diversity supported by higher available free energy. For both rings, the species diversity was highest near the borders of the 20-30 m broad ring edges.}, } @article {pmid30013303, year = {2018}, author = {Ramazzotti, D and Graudenzi, A and Caravagna, G and Antoniotti, M}, title = {Modeling Cumulative Biological Phenomena with Suppes-Bayes Causal Networks.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318785167}, pmid = {30013303}, issn = {1176-9343}, abstract = {Several diseases related to cell proliferation are characterized by the accumulation of somatic DNA changes, with respect to wild-type conditions. Cancer and HIV are 2 common examples of such diseases, where the mutational load in the cancerous/viral population increases over time. In these cases, selective pressures are often observed along with competition, co-operation, and parasitism among distinct cellular clones. Recently, we presented a mathematical framework to model these phenomena, based on a combination of Bayesian inference and Suppes' theory of probabilistic causation, depicted in graphical structures dubbed Suppes-Bayes Causal Networks (SBCNs). The SBCNs are generative probabilistic graphical models that recapitulate the potential ordering of accumulation of such DNA changes during the progression of the disease. Such models can be inferred from data by exploiting likelihood-based model selection strategies with regularization. In this article, we discuss the theoretical foundations of our approach and we investigate in depth the influence on the model selection task of (1) the poset based on Suppes' theory and (2) different regularization strategies. Furthermore, we provide an example of application of our framework to HIV genetic data highlighting the valuable insights provided by the inferred SBCN.}, } @article {pmid30013238, year = {2018}, author = {Guzzo, M and Murray, SM and Martineau, E and Lhospice, S and Baronian, G and My, L and Zhang, Y and Espinosa, L and Vincentelli, R and Bratton, BP and Shaevitz, JW and Molle, V and Howard, M and Mignot, T}, title = {A gated relaxation oscillator mediated by FrzX controls morphogenetic movements in Myxococcus xanthus.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {948-959}, doi = {10.1038/s41564-018-0203-x}, pmid = {30013238}, issn = {2058-5276}, abstract = {Dynamic control of cell polarity is of critical importance for many aspects of cellular development and motility. In Myxococcus xanthus, MglA, a G protein, and MglB, its cognate GTPase-activating protein, establish a polarity axis that defines the direction of movement of the cell and that can be rapidly inverted by the Frz chemosensory system. Although vital for collective cell behaviours, how Frz triggers this switch has remained unknown. Here, we use genetics, imaging and mathematical modelling to show that Frz controls polarity reversals via a gated relaxation oscillator. FrzX, which we identify as a target of the Frz kinase, provides the gating and thus acts as the trigger for reversals. Slow relocalization of the polarity protein RomR then creates a refractory period during which another switch cannot be triggered. A secondary Frz output, FrzZ, decreases this delay, allowing rapid reversals when required. Thus, this architecture results in a highly tuneable switch that allows a wide range of reversal frequencies.}, } @article {pmid30013237, year = {2018}, author = {Boldock, E and Surewaard, BGJ and Shamarina, D and Na, M and Fei, Y and Ali, A and Williams, A and Pollitt, EJG and Szkuta, P and Morris, P and Prajsnar, TK and McCoy, KD and Jin, T and Dockrell, DH and van Strijp, JAG and Kubes, P and Renshaw, SA and Foster, SJ}, title = {Human skin commensals augment Staphylococcus aureus pathogenesis.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {881-890}, pmid = {30013237}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; MR/K015753/1//Medical Research Council/United Kingdom ; }, abstract = {All bacterial infections occur within a polymicrobial environment, from which a pathogen population emerges to establish disease within a host. Emphasis has been placed on prevention of pathogen dominance by competing microflora acting as probiotics1. Here we show that the virulence of the human pathogen Staphylococcus aureus is augmented by native, polymicrobial, commensal skin flora and individual species acting as 'proinfectious agents'. The outcome is pathogen proliferation, but not commensal. Pathogenesis augmentation can be mediated by particulate cell wall peptidoglycan, reducing the S. aureus infectious dose by over 1,000-fold. This phenomenon occurs using a range of S. aureus strains and infection models and is not mediated by established receptor-mediated pathways including Nod1, Nod2, Myd88 and the NLPR3 inflammasome. During mouse sepsis, augmentation depends on liver-resident macrophages (Kupffer cells) that capture and internalize both the pathogen and the proinfectious agent, leading to reduced production of reactive oxygen species, pathogen survival and subsequent multiple liver abscess formation. The augmented infection model more closely resembles the natural situation and establishes the role of resident environmental microflora in the initiation of disease by an invading pathogen. As the human microflora is ubiquitous2, its role in increasing susceptibility to infection by S. aureus highlights potential strategies for disease prevention.}, } @article {pmid30013236, year = {2018}, author = {Emerson, JB and Roux, S and Brum, JR and Bolduc, B and Woodcroft, BJ and Jang, HB and Singleton, CM and Solden, LM and Naas, AE and Boyd, JA and Hodgkins, SB and Wilson, RM and Trubl, G and Li, C and Frolking, S and Pope, PB and Wrighton, KC and Crill, PM and Chanton, JP and Saleska, SR and Tyson, GW and Rich, VI and Sullivan, MB}, title = {Host-linked soil viral ecology along a permafrost thaw gradient.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {870-880}, doi = {10.1038/s41564-018-0190-y}, pmid = {30013236}, issn = {2058-5276}, abstract = {Climate change threatens to release abundant carbon that is sequestered at high latitudes, but the constraints on microbial metabolisms that mediate the release of methane and carbon dioxide are poorly understood1-7. The role of viruses, which are known to affect microbial dynamics, metabolism and biogeochemistry in the oceans8-10, remains largely unexplored in soil. Here, we aimed to investigate how viruses influence microbial ecology and carbon metabolism in peatland soils along a permafrost thaw gradient in Sweden. We recovered 1,907 viral populations (genomes and large genome fragments) from 197 bulk soil and size-fractionated metagenomes, 58% of which were detected in metatranscriptomes and presumed to be active. In silico predictions linked 35% of the viruses to microbial host populations, highlighting likely viral predators of key carbon-cycling microorganisms, including methanogens and methanotrophs. Lineage-specific virus/host ratios varied, suggesting that viral infection dynamics may differentially impact microbial responses to a changing climate. Virus-encoded glycoside hydrolases, including an endomannanase with confirmed functional activity, indicated that viruses influence complex carbon degradation and that viral abundances were significant predictors of methane dynamics. These findings suggest that viruses may impact ecosystem function in climate-critical, terrestrial habitats and identify multiple potential viral contributions to soil carbon cycling.}, } @article {pmid30013225, year = {2018}, author = {Strzyz, P}, title = {Concentrating on intrinsic disorder.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {534}, doi = {10.1038/s41576-018-0037-7}, pmid = {30013225}, issn = {1471-0064}, } @article {pmid30013205, year = {2018}, author = {Mehling, MA and van Asselt, H and Das, K and Droege, S}, title = {Beat protectionism and emissions at a stroke.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {321-324}, doi = {10.1038/d41586-018-05708-7}, pmid = {30013205}, issn = {1476-4687}, } @article {pmid30013204, year = {2018}, author = {Mooers, AO and Greenberg, DA}, title = {Speciation far from the madding crowd.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {341-342}, doi = {10.1038/d41586-018-05575-2}, pmid = {30013204}, issn = {1476-4687}, mesh = {Animals ; Biological Evolution ; *Ecology ; *Fishes ; Genetic Speciation ; Species Specificity ; }, } @article {pmid30013203, year = {2018}, author = {Siekmann, AF}, title = {Coronary artery development, one cell at a time.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {335-336}, doi = {10.1038/d41586-018-05463-9}, pmid = {30013203}, issn = {1476-4687}, mesh = {Coronary Artery Disease ; *Coronary Vessels ; Heart ; Organogenesis ; *Single-Cell Analysis ; Stem Cells ; }, } @article {pmid30013202, year = {2018}, author = {Galsky, MD}, title = {Resistance to prostate-cancer treatment is driven by immune cells.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {338-339}, doi = {10.1038/d41586-018-05460-y}, pmid = {30013202}, issn = {1476-4687}, mesh = {Biological Transport ; Cell Line, Tumor ; Drug Resistance, Neoplasm ; Humans ; Interleukin-23 ; Male ; Myeloid Cells ; *Prostatic Neoplasms ; *Prostatic Neoplasms, Castration-Resistant ; }, } @article {pmid30013184, year = {2018}, author = {Waage, J and Standl, M and Curtin, JA and Jessen, LE and Thorsen, J and Tian, C and Schoettler, N and , and , and Flores, C and Abdellaoui, A and Ahluwalia, TS and Alves, AC and Amaral, AFS and Antó, JM and Arnold, A and Barreto-Luis, A and Baurecht, H and van Beijsterveldt, CEM and Bleecker, ER and Bonàs-Guarch, S and Boomsma, DI and Brix, S and Bunyavanich, S and Burchard, EG and Chen, Z and Curjuric, I and Custovic, A and den Dekker, HT and Dharmage, SC and Dmitrieva, J and Duijts, L and Ege, MJ and Gauderman, WJ and Georges, M and Gieger, C and Gilliland, F and Granell, R and Gui, H and Hansen, T and Heinrich, J and Henderson, J and Hernandez-Pacheco, N and Holt, P and Imboden, M and Jaddoe, VWV and Jarvelin, MR and Jarvis, DL and Jensen, KK and Jónsdóttir, I and Kabesch, M and Kaprio, J and Kumar, A and Lee, YA and Levin, AM and Li, X and Lorenzo-Diaz, F and Melén, E and Mercader, JM and Meyers, DA and Myers, R and Nicolae, DL and Nohr, EA and Palviainen, T and Paternoster, L and Pennell, CE and Pershagen, G and Pino-Yanes, M and Probst-Hensch, NM and Rüschendorf, F and Simpson, A and Stefansson, K and Sunyer, J and Sveinbjornsson, G and Thiering, E and Thompson, PJ and Torrent, M and Torrents, D and Tung, JY and Wang, CA and Weidinger, S and Weiss, S and Willemsen, G and Williams, LK and Ober, C and Hinds, DA and Ferreira, MA and Bisgaard, H and Strachan, DP and Bønnelykke, K}, title = {Genome-wide association and HLA fine-mapping studies identify risk loci and genetic pathways underlying allergic rhinitis.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1072-1080}, doi = {10.1038/s41588-018-0157-1}, pmid = {30013184}, issn = {1546-1718}, abstract = {Allergic rhinitis is the most common clinical presentation of allergy, affecting 400 million people worldwide, with increasing incidence in westernized countries1,2. To elucidate the genetic architecture and understand the underlying disease mechanisms, we carried out a meta-analysis of allergic rhinitis in 59,762 cases and 152,358 controls of European ancestry and identified a total of 41 risk loci for allergic rhinitis, including 20 loci not previously associated with allergic rhinitis, which were confirmed in a replication phase of 60,720 cases and 618,527 controls. Functional annotation implicated genes involved in various immune pathways, and fine mapping of the HLA region suggested amino acid variants important for antigen binding. We further performed genome-wide association study (GWAS) analyses of allergic sensitization against inhalant allergens and nonallergic rhinitis, which suggested shared genetic mechanisms across rhinitis-related traits. Future studies of the identified loci and genes might identify novel targets for treatment and prevention of allergic rhinitis.}, } @article {pmid30013183, year = {2018}, author = {Li, G and Martínez-Bonet, M and Wu, D and Yang, Y and Cui, J and Nguyen, HN and Cunin, P and Levescot, A and Bai, M and Westra, HJ and Okada, Y and Brenner, MB and Raychaudhuri, S and Hendrickson, EA and Maas, RL and Nigrovic, PA}, title = {High-throughput identification of noncoding functional SNPs via type IIS enzyme restriction.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1180-1188}, pmid = {30013183}, issn = {1546-1718}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R21 NS096443/NS/NINDS NIH HHS/United States ; P30 AR070253/AR/NIAMS NIH HHS/United States ; R01 AR065538/AR/NIAMS NIH HHS/United States ; R21 AR070378/AR/NIAMS NIH HHS/United States ; }, abstract = {Genome-wide association studies (GWAS) have identified many disease-associated noncoding variants, but cannot distinguish functional single-nucleotide polymorphisms (fSNPs) from others that reside incidentally within risk loci. To address this challenge, we developed an unbiased high-throughput screen that employs type IIS enzymatic restriction to identify fSNPs that allelically modulate the binding of regulatory proteins. We coupled this approach, termed SNP-seq, with flanking restriction enhanced pulldown (FREP) to identify regulation of CD40 by three disease-associated fSNPs via four regulatory proteins, RBPJ, RSRC2 and FUBP-1/TRAP150. Applying this approach across 27 loci associated with juvenile idiopathic arthritis, we identified 148 candidate fSNPs, including two that regulate STAT4 via the regulatory proteins SATB2 and H1.2. Together, these findings establish the utility of tandem SNP-seq/FREP to bridge the gap between GWAS and disease mechanism.}, } @article {pmid30013182, year = {2018}, author = {Sulkowski, PL and Sundaram, RK and Oeck, S and Corso, CD and Liu, Y and Noorbakhsh, S and Niger, M and Boeke, M and Ueno, D and Kalathil, AN and Bao, X and Li, J and Shuch, B and Bindra, RS and Glazer, PM}, title = {Krebs-cycle-deficient hereditary cancer syndromes are defined by defects in homologous-recombination DNA repair.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1086-1092}, pmid = {30013182}, issn = {1546-1718}, support = {R01 ES005775/ES/NIEHS NIH HHS/United States ; T32 GM007223/GM/NIGMS NIH HHS/United States ; R01 CA215453/CA/NCI NIH HHS/United States ; R35 CA197574/CA/NCI NIH HHS/United States ; R01 CA168733/CA/NCI NIH HHS/United States ; }, abstract = {The hereditary cancer syndromes hereditary leiomyomatosis and renal cell cancer (HLRCC) and succinate dehydrogenase-related hereditary paraganglioma and pheochromocytoma (SDH PGL/PCC) are linked to germline loss-of-function mutations in genes encoding the Krebs cycle enzymes fumarate hydratase and succinate dehydrogenase, thus leading to elevated levels of fumarate and succinate, respectively1-3. Here, we report that fumarate and succinate both suppress the homologous recombination (HR) DNA-repair pathway required for the resolution of DNA double-strand breaks (DSBs) and for the maintenance of genomic integrity, thus rendering tumor cells vulnerable to synthetic-lethal targeting with poly(ADP)-ribose polymerase (PARP) inhibitors. These results identify HLRCC and SDH PGL/PCC as familial DNA-repair deficiency syndromes, providing a mechanistic basis to explain their cancer predisposition and suggesting a potentially therapeutic approach for advanced HLRCC and SDH PGL/PCC, both of which are incurable when metastatic.}, } @article {pmid30013181, year = {2018}, author = {Schaffer, AE and Breuss, MW and Caglayan, AO and Al-Sanaa, N and Al-Abdulwahed, HY and Kaymakçalan, H and Yılmaz, C and Zaki, MS and Rosti, RO and Copeland, B and Baek, ST and Musaev, D and Scott, EC and Ben-Omran, T and Kariminejad, A and Kayserili, H and Mojahedi, F and Kara, M and Cai, N and Silhavy, JL and Elsharif, S and Fenercioglu, E and Barshop, BA and Kara, B and Wang, R and Stanley, V and James, KN and Nachnani, R and Kalur, A and Megahed, H and Incecik, F and Danda, S and Alanay, Y and Faqeih, E and Melikishvili, G and Mansour, L and Miller, I and Sukhudyan, B and Chelly, J and Dobyns, WB and Bilguvar, K and Jamra, RA and Gunel, M and Gleeson, JG}, title = {Biallelic loss of human CTNNA2, encoding αN-catenin, leads to ARP2/3 complex overactivity and disordered cortical neuronal migration.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1093-1101}, pmid = {30013181}, issn = {1546-1718}, support = {P30 NS047101/NS/NINDS NIH HHS/United States ; R01 NS041537/NS/NINDS NIH HHS/United States ; R01 NS048453/NS/NINDS NIH HHS/United States ; K99 HD082337/HD/NICHD NIH HHS/United States ; R01 NS052455/NS/NINDS NIH HHS/United States ; P01 HD070494/HD/NICHD NIH HHS/United States ; R00 HD082337/HD/NICHD NIH HHS/United States ; }, abstract = {Neuronal migration defects, including pachygyria, are among the most severe developmental brain defects in humans. Here, we identify biallelic truncating mutations in CTNNA2, encoding αN-catenin, in patients with a distinct recessive form of pachygyria. CTNNA2 was expressed in human cerebral cortex, and its loss in neurons led to defects in neurite stability and migration. The αN-catenin paralog, αE-catenin, acts as a switch regulating the balance between β-catenin and Arp2/3 actin filament activities1. Loss of αN-catenin did not affect β-catenin signaling, but recombinant αN-catenin interacted with purified actin and repressed ARP2/3 actin-branching activity. The actin-binding domain of αN-catenin or ARP2/3 inhibitors rescued the neuronal phenotype associated with CTNNA2 loss, suggesting ARP2/3 de-repression as a potential disease mechanism. Our findings identify CTNNA2 as the first catenin family member with biallelic mutations in humans, causing a new pachygyria syndrome linked to actin regulation, and uncover a key factor involved in ARP2/3 repression in neurons.}, } @article {pmid30013180, year = {2018}, author = {Zhou, J and Theesfeld, CL and Yao, K and Chen, KM and Wong, AK and Troyanskaya, OG}, title = {Deep learning sequence-based ab initio prediction of variant effects on expression and disease risk.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1171-1179}, pmid = {30013180}, issn = {1546-1718}, support = {HHSN272201000054C/AI/NIAID NIH HHS/United States ; U54 HL117798/HL/NHLBI NIH HHS/United States ; R01 GM071966/GM/NIGMS NIH HHS/United States ; U19 AI117873/AI/NIAID NIH HHS/United States ; R01 HG005998/HG/NHGRI NIH HHS/United States ; }, abstract = {Key challenges for human genetics, precision medicine and evolutionary biology include deciphering the regulatory code of gene expression and understanding the transcriptional effects of genome variation. However, this is extremely difficult because of the enormous scale of the noncoding mutation space. We developed a deep learning-based framework, ExPecto, that can accurately predict, ab initio from a DNA sequence, the tissue-specific transcriptional effects of mutations, including those that are rare or that have not been observed. We prioritized causal variants within disease- or trait-associated loci from all publicly available genome-wide association studies and experimentally validated predictions for four immune-related diseases. By exploiting the scalability of ExPecto, we characterized the regulatory mutation space for human RNA polymerase II-transcribed genes by in silico saturation mutagenesis and profiled > 140 million promoter-proximal mutations. This enables probing of evolutionary constraints on gene expression and ab initio prediction of mutation disease effects, making ExPecto an end-to-end computational framework for the in silico prediction of expression and disease risk.}, } @article {pmid30013179, year = {2018}, author = {Bielski, CM and Zehir, A and Penson, AV and Donoghue, MTA and Chatila, W and Armenia, J and Chang, MT and Schram, AM and Jonsson, P and Bandlamudi, C and Razavi, P and Iyer, G and Robson, ME and Stadler, ZK and Schultz, N and Baselga, J and Solit, DB and Hyman, DM and Berger, MF and Taylor, BS}, title = {Genome doubling shapes the evolution and prognosis of advanced cancers.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1189-1195}, pmid = {30013179}, issn = {1546-1718}, support = {U54 OD020355/OD/NIH HHS/United States ; R01 CA207244/CA/NCI NIH HHS/United States ; P50 CA092629/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; T32 GM007175/GM/NIGMS NIH HHS/United States ; R01 CA204749/CA/NCI NIH HHS/United States ; }, abstract = {Ploidy abnormalities are a hallmark of cancer, but their impact on the evolution and outcomes of cancers is unknown. Here, we identified whole-genome doubling (WGD) in the tumors of nearly 30% of 9,692 prospectively sequenced advanced cancer patients. WGD varied by tumor lineage and molecular subtype, and arose early in carcinogenesis after an antecedent transforming driver mutation. While associated with TP53 mutations, 46% of all WGD arose in TP53-wild-type tumors and in such cases was associated with an E2F-mediated G1 arrest defect, although neither aberration was obligate in WGD tumors. The variability of WGD across cancer types can be explained in part by cancer cell proliferation rates. WGD predicted for increased morbidity across cancer types, including KRAS-mutant colorectal cancers and estrogen receptor-positive breast cancers, independently of established clinical prognostic factors. We conclude that WGD is highly common in cancer and is a macro-evolutionary event associated with poor prognosis across cancer types.}, } @article {pmid30013178, year = {2018}, author = {Kowalec, K and Wright, GEB and Drögemöller, BI and Aminkeng, F and Bhavsar, AP and Kingwell, E and Yoshida, EM and Traboulsee, A and Marrie, RA and Kremenchutzky, M and Campbell, TL and Duquette, P and Chalasani, N and Wadelius, M and Hallberg, P and Xia, Z and De Jager, PL and Denny, JC and Davis, MF and Ross, CJD and Tremlett, H and Carleton, BC}, title = {Common variation near IRF6 is associated with IFN-β-induced liver injury in multiple sclerosis.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1081-1085}, doi = {10.1038/s41588-018-0168-y}, pmid = {30013178}, issn = {1546-1718}, abstract = {Multiple sclerosis (MS) is a disease of the central nervous system treated with disease-modifying therapies, including the biologic, interferon-β (IFN-β). Up to 60% of IFN-β-exposed MS patients develop abnormal biochemical liver test results1,2, and 1 in 50 experiences drug-induced liver injury3. Since genomic variation contributes to other forms of drug-induced liver injury4,5, we aimed to identify biomarkers of IFN-β-induced liver injury using a two-stage genome-wide association study. The rs2205986 variant, previously linked to differential expression of IRF6, surpassed genome-wide significance in the combined two-stage analysis (P = 2.3 × 10-8, odds ratio = 8.3, 95% confidence interval = 3.6-19.2). Analysis of an independent cohort of IFN-β-treated MS patients identified via electronic medical records showed that rs2205986 was also associated with increased peak levels of aspartate aminotransferase (P = 7.6 × 10-5) and alkaline phosphatase (P = 4.9 × 10-4). We show that these findings may be applicable to predicting IFN-β-induced liver injury, offering insight into its safer use.}, } @article {pmid30013133, year = {2018}, author = {Metcalfe, DB and Hermans, TDG and Ahlstrand, J and Becker, M and Berggren, M and Björk, RG and Björkman, MP and Blok, D and Chaudhary, N and Chisholm, C and Classen, AT and Hasselquist, NJ and Jonsson, M and Kristensen, JA and Kumordzi, BB and Lee, H and Mayor, JR and Prevéy, J and Pantazatou, K and Rousk, J and Sponseller, RA and Sundqvist, MK and Tang, J and Uddling, J and Wallin, G and Zhang, W and Ahlström, A and Tenenbaum, DE and Abdi, AM}, title = {Patchy field sampling biases understanding of climate change impacts across the Arctic.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1443-1448}, doi = {10.1038/s41559-018-0612-5}, pmid = {30013133}, issn = {2397-334X}, abstract = {Effective societal responses to rapid climate change in the Arctic rely on an accurate representation of region-specific ecosystem properties and processes. However, this is limited by the scarcity and patchy distribution of field measurements. Here, we use a comprehensive, geo-referenced database of primary field measurements in 1,840 published studies across the Arctic to identify statistically significant spatial biases in field sampling and study citation across this globally important region. We find that 31% of all study citations are derived from sites located within 50 km of just two research sites: Toolik Lake in the USA and Abisko in Sweden. Furthermore, relatively colder, more rapidly warming and sparsely vegetated sites are under-sampled and under-recognized in terms of citations, particularly among microbiology-related studies. The poorly sampled and cited areas, mainly in the Canadian high-Arctic archipelago and the Arctic coastline of Russia, constitute a large fraction of the Arctic ice-free land area. Our results suggest that the current pattern of sampling and citation may bias the scientific consensuses that underpin attempts to accurately predict and effectively mitigate climate change in the region. Further work is required to increase both the quality and quantity of sampling, and incorporate existing literature from poorly cited areas to generate a more representative picture of Arctic climate change and its environmental impacts.}, } @article {pmid30013132, year = {2018}, author = {Menge, DNL and MacPherson, AC and Bytnerowicz, TA and Quebbeman, AW and Schwartz, NB and Taylor, BN and Wolf, AA}, title = {Logarithmic scales in ecological data presentation may cause misinterpretation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1393-1402}, doi = {10.1038/s41559-018-0610-7}, pmid = {30013132}, issn = {2397-334X}, abstract = {Scientific communication relies on clear presentation of data. Logarithmic scales are used frequently for data presentation in many scientific disciplines, including ecology, but the degree to which they are correctly interpreted by readers is unclear. Analysing the extent of log scales in the literature, we show that 22% of papers published in the journal Ecology in 2015 included at least one log-scaled axis, of which 21% were log-log displays. We conducted a survey that asked members of the Ecological Society of America (988 responses, and 623 completed surveys) to interpret graphs that were randomly displayed with linear-linear or log-log axes. Many more respondents interpreted graphs correctly when the graphs had linear-linear axes than when they had log-log axes: 93% versus 56% for our all-around metric, although some of the individual item comparisons were even more skewed (for example, 86% versus 9% and 88% versus 12%). These results suggest that misconceptions about log-scaled data are rampant. We recommend that ecology curricula include explicit instruction on how to interpret log-scaled axes and equations, and we also recommend that authors take the potential for misconceptions into account when deciding how to visualize data.}, } @article {pmid30013131, year = {2018}, author = {Loughlin, NJD and Gosling, WD and Mothes, P and Montoya, E}, title = {Ecological consequences of post-Columbian indigenous depopulation in the Andean-Amazonian corridor.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1233-1236}, doi = {10.1038/s41559-018-0602-7}, pmid = {30013131}, issn = {2397-334X}, abstract = {European colonization of South America instigated a continental-scale depopulation of its indigenous peoples. The impact of depopulation on the tropical forests of South America varied across the continent. Furthermore, the role that indigenous peoples played in transforming the biodiverse tropical forests of the Andean-Amazonian corridor before AD 1492 remains unknown. Here, we reconstruct the past 1,000 years of changing human impact on the cloud forest of Ecuador at a key trade route, which connected the Inkan Empire to the peoples of Amazonia. We compare this historical landscape with the pre-human arrival (around 44,000-42,000 years ago) and modern environments. We demonstrate that intensive land-use within the cloud forest before European arrival deforested the landscape to a greater extent than modern (post-AD 1950) cattle farming. Intensive indigenous land-use ended abruptly around AD 1588 following a catastrophic population decline. Forest succession then took around 130 years to establish a structurally intact forest-one comparable to that which occurred before the arrival of the first humans to the continent. We show that nineteenth-century descriptions of the Andean-Amazonian corridor as a pristine wilderness record a shifted ecological baseline-one that less than 250 years earlier had consisted of a heavily managed and cultivated landscape.}, } @article {pmid30013121, year = {2018}, author = {Que, X and Hung, MY and Yeang, C and Gonen, A and Prohaska, TA and Sun, X and Diehl, C and Määttä, A and Gaddis, DE and Bowden, K and Pattison, J and MacDonald, JG and Ylä-Herttuala, S and Mellon, PL and Hedrick, CC and Ley, K and Miller, YI and Glass, CK and Peterson, KL and Binder, CJ and Tsimikas, S and Witztum, JL}, title = {Publisher Correction: Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {E43}, doi = {10.1038/s41586-018-0313-x}, pmid = {30013121}, issn = {1476-4687}, abstract = {In this Letter, affiliation number 1 was originally missing from the HTML; the affiliations were missing for author Ming-Yow Hung in the HTML; and the Fig. 4 legend erroneously referred to panels a-h, instead of a-g. These errors have been corrected online.}, } @article {pmid30013120, year = {2018}, author = {Nusse, YM and Savage, AK and Marangoni, P and Rosendahl-Huber, AKM and Landman, TA and de Sauvage, FJ and Locksley, RM and Klein, OD}, title = {Publisher Correction: Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche.}, journal = {Nature}, volume = {562}, number = {7727}, pages = {E22}, doi = {10.1038/s41586-018-0370-1}, pmid = {30013120}, issn = {1476-4687}, abstract = {In this Letter, the received date should have been 23 March 2017 instead of 13 April 2018. Authors R.M.K. and O.D.K. were incorrectly denoted as 'equally contributing' authors. The labels for 'control' and 'IFNγ' in Extended Data Fig. 4g were reversed. These have been corrected online.}, } @article {pmid30013119, year = {2018}, author = {Liu, X and Zhang, F and Jing, X and Pan, M and Liu, P and Li, W and Zhu, B and Li, J and Chen, H and Wang, L and Lin, J and Liu, Y and Zhao, D and Yan, H and Fan, C}, title = {Complex silica composite nanomaterials templated with DNA origami.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {593-598}, doi = {10.1038/s41586-018-0332-7}, pmid = {30013119}, issn = {1476-4687}, mesh = {Biomimetics ; DNA/*chemistry/ultrastructure ; Elastic Modulus ; Microscopy, Electron, Transmission ; Molecular Dynamics Simulation ; Nanostructures/*chemistry/ultrastructure ; Silicon Dioxide/*chemistry ; }, abstract = {Genetically encoded protein scaffolds often serve as templates for the mineralization of biocomposite materials with complex yet highly controlled structural features that span from nanometres to the macroscopic scale1-4. Methods developed to mimic these fabrication capabilities can produce synthetic materials with well defined micro- and macro-sized features, but extending control to the nanoscale remains challenging5,6. DNA nanotechnology can deliver a wide range of customized nanoscale two- and three-dimensional assemblies with controlled sizes and shapes7-11. But although DNA has been used to modulate the morphology of inorganic materials12,13 and DNA nanostructures have served as moulds14,15 and templates16,17, it remains challenging to exploit the potential of DNA nanostructures fully because they require high-ionic-strength solutions to maintain their structure, and this in turn gives rise to surface charging that suppresses the material deposition. Here we report that the Stöber method, widely used for producing silica (silicon dioxide) nanostructures, can be adjusted to overcome this difficulty: when synthesis conditions are such that mineral precursor molecules do not deposit directly but first form clusters, DNA-silica hybrid materials that faithfully replicate the complex geometric information of a wide range of different DNA origami scaffolds are readily obtained. We illustrate this approach using frame-like, curved and porous DNA nanostructures, with one-, two- and three-dimensional complex hierarchical architectures that range in size from 10 to 1,000 nanometres. We also show that after coating with an amorphous silica layer, the thickness of which can be tuned by adjusting the growth time, hybrid structures can be up to ten times tougher than the DNA template while maintaining flexibility. These findings establish our approach as a general method for creating biomimetic silica nanostructures.}, } @article {pmid30013118, year = {2018}, author = {Woodcroft, BJ and Singleton, CM and Boyd, JA and Evans, PN and Emerson, JB and Zayed, AAF and Hoelzle, RD and Lamberton, TO and McCalley, CK and Hodgkins, SB and Wilson, RM and Purvine, SO and Nicora, CD and Li, C and Frolking, S and Chanton, JP and Crill, PM and Saleska, SR and Rich, VI and Tyson, GW}, title = {Genome-centric view of carbon processing in thawing permafrost.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {49-54}, doi = {10.1038/s41586-018-0338-1}, pmid = {30013118}, issn = {1476-4687}, mesh = {Bacteria/genetics/isolation & purification/metabolism ; Carbon/*metabolism ; Fermentation ; *Freezing ; Fungi/genetics/isolation & purification/metabolism ; Global Warming ; Metagenome/*genetics ; Methane/metabolism ; Permafrost/*chemistry/*microbiology ; Polysaccharides/metabolism ; *Soil Microbiology ; Sweden ; Xylose/metabolism ; }, abstract = {As global temperatures rise, large amounts of carbon sequestered in permafrost are becoming available for microbial degradation. Accurate prediction of carbon gas emissions from thawing permafrost is limited by our understanding of these microbial communities. Here we use metagenomic sequencing of 214 samples from a permafrost thaw gradient to recover 1,529 metagenome-assembled genomes, including many from phyla with poor genomic representation. These genomes reflect the diversity of this complex ecosystem, with genus-level representatives for more than sixty per cent of the community. Meta-omic analysis revealed key populations involved in the degradation of organic matter, including bacteria whose genomes encode a previously undescribed fungal pathway for xylose degradation. Microbial and geochemical data highlight lineages that correlate with the production of greenhouse gases and indicate novel syntrophic relationships. Our findings link changing biogeochemistry to specific microbial lineages involved in carbon processing, and provide key information for predicting the effects of climate change on permafrost systems.}, } @article {pmid30012750, year = {2018}, author = {Orschiedt, J}, title = {The Late Upper Palaeolithic and earliest Mesolithic evidence of burials in Europe.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012750}, issn = {1471-2970}, abstract = {Burials of the Late Palaeolithic (14 000-11 600 cal years before present, henceforth BP) are a rare phenomenon in Europe. Several sites possess burials of single and double individuals. As with the preceding Magdalenian, the burial of more than two individuals in the same grave cutting seems to be unusual, but does occur occasionally. The deposition of isolated and disarticulated human remains with or without cut marks seems additionally to belong to the Magdalenian context. In the final Palaeolithic phase (13 000-11 600 cal years BP) there is evidence for cemetery-like clusters of burials, which contrast to the Magdalenian evidence, instead showing some similarities with the succeeding Mesolithic. The earliest Mesolithic burials 11 600-10 500 cal BP) are a very rare phenomenon, covering a short time span between the beginning of the Preboreal and the beginning of the Boreal phase of the early Holocene. Here the evidence includes single inhumations, cemetery-like structures and a number of isolated human remains. Caves and rock shelters were the most common places for inhumations in both the final Palaeolithic and the early Mesolithic. Although the number of sites with a chronological continuity from the LUP to the Early Mesolithic burial is low, several aspects indicate a general continuity in burial patterns over this period. Apart from this continuity, the Mesolithic burials in general seem to represent a new level of diversity in burial practices.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012749, year = {2018}, author = {Gonçalves, A and Biro, D}, title = {Comparative thanatology, an integrative approach: exploring sensory/cognitive aspects of death recognition in vertebrates and invertebrates.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012749}, issn = {1471-2970}, abstract = {Evolutionary thanatology benefits from broad taxonomic comparisons of non-human animals' responses to death. Furthermore, exploring the sensory and cognitive bases of these responses promises to allow classification of the underlying mechanisms on a spectrum from phylogenetically ancient to more derived traits. We draw on studies of perception and cognition in invertebrate and vertebrate taxa (with a focus on arthropods, corvids, proboscids, cetaceans and primates) to explore the cues that these animals use to detect life and death in others, and discuss proximate and ultimate drivers behind their capacities to do so. Parallels in thanatological behaviour exhibited by the last four taxa suggest similar sensory-cognitive processing rules for dealing with corpses, the evolution of which may have been driven by complex social environments. Uniting these responses is a phenomenon we term 'animacy detection malfunction', whereupon the corpse, having both animate and inanimate attributes, creates states of fear/curiosity manifested as approach/avoidance behaviours in observers. We suggest that integrating diverse lines of evidence (including the 'uncanny valley' effect originating from the field of robotics) provides a promising way to advance the field, and conclude by proposing avenues for future research.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012748, year = {2018}, author = {Anderson, JR and Biro, D and Pettitt, P}, title = {Evolutionary thanatology.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012748}, issn = {1471-2970}, abstract = {Societies, including those of humans, have evolved multiple ways of dealing with death across changing circumstances and pressures. Despite many studies focusing on specialized topics, for example necrophoresis in eusocial insects, mortuary activities in early human societies, or grief and mourning in bereavement, there has been little attempt to consider these disparate research endeavours from a broader evolutionary perspective. Evolutionary thanatology does this by adopting an explicit evolutionary stance for studies of death and dying within the sociological, psychological and biological disciplines. The collection of papers in this themed issue demonstrates the value of this approach by describing what is known about how various nonhuman species detect and respond to death in conspecifics, how problems of disposing of the dead have evolved in human societies across evolutionary time and also within much shorter time frames, how human adults' understanding of death develops, and how it is ultimately reflected in death-related language. The psychological significance and impact of death is clearly seen in some species' grief-like reactions to the loss of attachment figures, and perhaps uniquely in humans, the existence of certain psychological processes that may lead to suicide. Several research questions are proposed as starting points for building a more comprehensive picture of the ontogeny and phylogeny of how organisms deal with death.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012747, year = {2018}, author = {Watson, CFI and Matsuzawa, T}, title = {Behaviour of nonhuman primate mothers toward their dead infants: uncovering mechanisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012747}, issn = {1471-2970}, abstract = {In comparative thanatology, most reports for nonhuman mammals concern mothers' behavioural responses to their dead offspring: most prominently, dead-infant carrying (sometimes of extended duration); but also inspection, proximity, maternal care such as grooming, protective behaviours and filial cannibalism. Documented across many primate species, these behaviours remain poorly understood in all. The literature is dominated by relatively brief qualitative descriptions of isolated anecdotal cases in apes and monkeys. We argue for quantitative coding in case reports, alongside analyses of longitudinal records of such events to allow objective evaluation of competing theories, and systematic comparisons within and across species and populations. Obtaining necessary datasets depends on raised awareness in researchers of the importance of recording occurrences and knowledge of pertinent data to collect. We review proposed explanatory hypotheses and outline data needed to test each empirically. To determine factors influencing infant-corpse carriage, we suggest analyses of deaths resulting in 'carry' versus 'no carry'. For individual cases, we highlight behavioural variables to code and the need for hormonal samples. We discuss mothers' stress and welfare in relation to infant death, continued transportation and premature removal of the corpse. Elucidating underlying proximate and ultimate causes is important for understanding phylogeny of maternal responses to infant death.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012746, year = {2018}, author = {Reggente, MALV and Papale, E and McGinty, N and Eddy, L and de Lucia, GA and Bertulli, CG}, title = {Social relationships and death-related behaviour in aquatic mammals: a systematic review.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012746}, issn = {1471-2970}, abstract = {Some aquatic mammals appear to care for their dead, whereas others abandon their live offspring when conditions are unfavourable. This incredible variety in behaviours suggests the importance of comparing and contrasting mechanisms driving death-related behaviours among these species. We reviewed 106 cases of aquatic mammals (81 cetaceans and 25 non-cetaceans) reacting to a death event, and extrapolated 'participant' (age class, sex, relationship and decomposition) and 'social' characteristics (escorting, calf dependence, alloparental care, herding and dispersal patterns) from published and unpublished literature. A multiple correspondence analysis (MCA) was performed to explore the relationships between these characteristics and death-related behaviours, with species clustered based on MCA scores. Results showed that both cetaceans and non-cetaceans react to death but in different ways. Non-cetaceans, characterized by a short maternal investment, were observed to protect the dead (defending it from external attacks), while cetaceans spent much longer with their offspring and display carrying (hauling, spinning, mouthing with the carcass and diving with it) and breathing-related (lifting and sinking the carcass) activities with the dead generally in association with other conspecifics. Our work emphasizes the need of increased documentation of death-related cases around the world to improve our understanding of aquatic mammals and their responses to death.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012745, year = {2018}, author = {Swift, K and Marzluff, JM}, title = {Occurrence and variability of tactile interactions between wild American crows and dead conspecifics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012745}, issn = {1471-2970}, abstract = {Observations of some mammals and birds touching their dead provoke questions about the motivation and adaptive value of this potentially risky behaviour. Here, we use controlled experiments to determine if tactile interactions are characteristic of wild American crow responses to dead crows, and what the prevalence and nature of tactile interactions suggests about their motivations. In Experiment 1, we test if food or information acquisition motivates contact by presenting crows with taxidermy-prepared dead crows, and two species crows are known to scavenge: dead pigeons and dead squirrels. In Experiment 2, we test if territoriality motivates tactile interactions by presenting crows with taxidermy crows prepared to look either dead or upright and life-like. In Experiment 1, we find that crows are significantly less likely to make contact but more likely to alarm call and recruit other birds in response to dead crows than to dead pigeons and squirrels. In addition, we find that aggressive and sexual encounters with dead crows are seasonally biased. These findings are inconsistent with feeding or information acquisition-based motivation. In Experiment 2, we find that crows rarely dive-bomb and more often alarm call and recruit other crows to dead than to life-like crows, behaviours inconsistent with responses given to live intruders. Consistent with a danger response hypothesis, our results show that alarm calling and neighbour recruitment occur more frequently in response to dead crows than other stimuli, and that touching dead crows is atypical. Occasional contacts, which take a variety of aggressive and sexual forms, may result from an inability to mediate conflicting stimuli.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012744, year = {2018}, author = {Sun, Q and Haynes, KF and Zhou, X}, title = {Managing the risks and rewards of death in eusocial insects.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012744}, issn = {1471-2970}, abstract = {Eusocial insects frequently face death of colony members as a consequence of living in large groups where the success of the colony is not dependent on the fate of the individual. Whereas death of conspecifics commonly triggers aversion in many group-living species due to risk of pathogens, eusocial insects perform cooperative corpse management. The causes and social context of the death, as well as feeding and nesting ecology of the species, influence the way that corpses are treated. The corpse itself releases cues that dictate the colony's response. As a result, social insects exhibit behavioural responses that promote disease resistance, colony defence and nutrient recycling. Corpse management represents a unique adaption that enhances colony success, and is another factor that has enabled eusocial insects to be so successful. In this review, we summarize the causes of death, the sensory detection of death and corpse management strategies of social insects. In addition, we provide insights into the evolution of behavioural response to the dead and the ecological relevance of corpse management.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012743, year = {2018}, author = {Anderson, JR}, title = {Chimpanzees and death.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012743}, issn = {1471-2970}, abstract = {Information about responses to death in nonhuman primates is important for evolutionary thanatology. This paper reviews the major causes of death in chimpanzees, and how these apes respond to cues related to dying and death. Topics covered include disease, human activities, predation, accidents and intra-species aggression and cannibalism. Chimpanzees also kill and sometimes eat other species. It is argued that, given their cognitive abilities, their experiences of death in conspecifics and other species are likely to equip chimpanzees with an understanding of death as cessation of function and irreversible. Whether they might understand that death is inevitable-including their own death, and biological causes of death is also discussed. As well as gathering more fundamental information about responses to dying and death, researchers should pay attention to possible cultural variations in how great apes deal with death.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012742, year = {2018}, author = {Pettitt, P}, title = {Hominin evolutionary thanatology from the mortuary to funerary realm: the palaeoanthropological bridge between chemistry and culture.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012742}, issn = {1471-2970}, abstract = {Palaeoanthropology, or more precisely Palaeolithic archaeology, offers the possibility of bridging the gap between mortuary activities that can be observed in the wider animal community and which relate to chemistry and emotion; to the often-elaborate systems of rationalization and symbolic contextualisation that are characteristic of recently observable societies. I draw on ethological studies to provide a core set of mortuary behaviours one might expect hominoids to inherit, and on anthropological observations to explore funerary activity represented in the Middle and Upper Palaeolithic, in order to examine how a distinctly human set of funerary behaviours arose from a more widespread set of mortuary behaviours. I suggest that the most profound innovation of the hominins was the incorporation of places into the commemoration of the dead, and propose a falsifiable mechanism for why this came about; and I suggest that the pattern of the earliest burials fits with modern hunter-gatherer belief systems about death, and how these vary by social complexity. Finally, I propose several research questions pertaining to the social context of funerary practices, suggesting how a hominin evolutionary thanatology may contribute not only to our understanding of human behavioural evolution, but to a wider thanatology of the animal kingdom.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012741, year = {2018}, author = {Husband, EM}, title = {Speaking of death.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012741}, issn = {1471-2970}, abstract = {As a human-specific trait, language offers a unique window on human cognition. Grammatical constraints on the ways we speak about events, for instance, have long been thought to reveal the representational formats that our minds impose on the ways that we think about events. In recent research, verbs that name events of death have stood out as key counterexamples to standard theories of the grammatical constraints on possible verbs. The special status of these thanatological verbs raises two important questions: why, given the vast number of verbs in any language, is it that verbs of death hold this special status, and what do they tell us about the restrictions on the representational format for possible verbs? This paper reexamines the evidence coming from verbs of death, confirming that they are counterexamples to standard theories, but that their behaviour suggests a more revealing constraint on our mental representations-that our minds impose strict restrictions on the format of asserted meaning. Thus, the constraints on linguistic representation and the human mind offer a unique perspective on the mental representations of thanatological phenomena.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012740, year = {2018}, author = {Shimane, K}, title = {Social bonds with the dead: how funerals transformed in the twentieth and twenty-first centuries.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012740}, issn = {1471-2970}, abstract = {Evolutionary thanatology includes the study of necrophoresis-the removal of dead individuals by the living among social insects. In human societies, 'necrophoresis' is performed via the funeral ceremony. In pre-modern societies, relatives and local community members helped to conduct funerals. In this way, holding a funeral was a form of mutual help, a social exchange of duty and responsibility essential to individuals. These societies developed systems to ensure the survival of humans as social animals based on mutual trust built over long periods of time within the same community. Contemporary societies are undermining these systems. Compared to funerals in pre-modern societies, holding a funeral in a modern society is a complicated process that requires professionals with specialized knowledge and skills. If people feel they can face mortality without support from relatives or the local community, and that they cannot necessarily expect a future return on the effort invested in community-based social relationships, they may begin to disengage from such relationships. In the context of modernization, the clearest changes in collective funerary behaviours include decreased funeral attendance and the above-mentioned outsourcing of funerary services. As such, it can be said that bonds with the dead changed completely under modernization, especially in the twentieth and twenty-first centuries. To establish a sociology of death with a clearer focus on how funeral ceremonies have been affected by modernization, there is a need for research concerned with human behavioural changes regarding the treatment of corpses-that is, a 'funeralogy'. Accordingly, this study aimed to investigate how modernization has complexified the handling of deceased bodies as death-related services have become commoditized and outsourced while, at the same time, local communities are becoming disengaged from their traditional roles in funeral ceremonies. To this end, fieldwork was conducted in several countries. Moreover, data from surveys conducted by the Social Well-Being Research Consortium in Asia in five East and Southeast Asian countries were quantitatively analysed. The findings highlight the modernization of funerals with the outsourcing of funeral services from the perspective of socio-economic development.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012739, year = {2018}, author = {Nakajima, S}, title = {Complicated grief: recent developments in diagnostic criteria and treatment.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012739}, issn = {1471-2970}, abstract = {Although grief is a natural response to loss among human beings, some people have a severe and prolonged course of grief. In the 1990s, unusual grief persisting with a high level of acute symptoms became known as 'complicated grief (CG)'. Many studies have shown that people who suffer from CG are at risk of long-term mental and physical health impairments and suicidal behaviours; it is considered a pathological state, which requires clinical intervention and treatment. DSM-5 (2013 Diagnostic and statistical manual of mental disorders, 5th edn) proposed 'persistent complex bereavement disorder' as a psychiatric disorder; it is similar to CG in that it is a trauma- and stress-related disorder. In recent years, there has been considerable research on the treatment of CG. Randomized controlled trials have suggested the efficacy of cognitive behavioural therapy including an exposure component that is targeted for CG. However, experts disagree about the terminology and diagnostic criteria for CG. The ICD-11 (International classification of diseases, 11th revision) beta draft proposed prolonged grief disorder as a condition that differs from persistent complex bereavement disorder with respect to terminology and the duration of symptoms. This divergence has arisen from insufficient evidence for a set of core symptoms and the biological basis of CG. Future studies including biological studies are needed to reach consensus about the diagnostic criteria for CG.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012738, year = {2018}, author = {Matsumoto, N}, title = {Changing relationship between the dead and the living in Japanese prehistory.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012738}, issn = {1471-2970}, abstract = {The aim of this paper is to propose a new insight on the changing burial practice by regarding it as a part of the cognitive system for maintaining complex social relationships. Development of concentrated burials and their transformation in Japanese prehistory are examined to present a specific case of the changing relationship between the dead and the living to highlight the significance of the dead in sociocultural evolution. The essential feature of the burial practices observed at Jomon sites is the centrality of the dead and their continuous presence in the kinship system. The mortuary practices discussed in this paper represent a close relationship between the dead and the living in the non-hierarchical complex society, in which the dead were not detached from the society, but kept at its core, as a materialized reference of kin networks.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012737, year = {2018}, author = {Luper, S}, title = {The moral standing of the dead.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, doi = {10.1098/rstb.2017.0270}, pmid = {30012737}, issn = {1471-2970}, abstract = {In choosing to do certain things, we appear to presuppose that we can act in the interests the dead, and that we have a duty to do so. For example, some of us go to great lengths to carry out their final wishes. Given that the dead no longer exist, however, it seems that nothing can be good or bad for them: they lack prudential interests. In that case, it is hard to see how we could owe them anything. They seem to lack moral standing altogether. In this essay, I will rebut this line of thought. I will claim that in some cases things that happen after people die are indeed good or bad for them. Their interests can still be advanced or hindered, so the dead have moral standing.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012736, year = {2018}, author = {Humphrey, N}, title = {The lure of death: suicide and human evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012736}, issn = {1471-2970}, abstract = {At some point in evolutionary history, human beings came to understand, as no non-human animals do, that death brings to an end a person's bodily and mental presence in the world. A potentially devastating consequence was that individuals, seeking to escape physical or mental pain, might choose to kill themselves.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012735, year = {2018}, author = {O'Connor, RC and Kirtley, OJ}, title = {The integrated motivational-volitional model of suicidal behaviour.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012735}, issn = {1471-2970}, abstract = {Suicide is a major public health concern accounting for 800 000 deaths globally each year. Although there have been many advances in understanding suicide risk in recent decades, our ability to predict suicide is no better now than it was 50 years ago. There are many potential explanations for this lack of progress, but the absence, until recently, of comprehensive theoretical models that predict the emergence of suicidal ideation distinct from the transition between suicidal ideation and suicide attempts/suicide is key to this lack of progress. The current article presents the integrated motivational-volitional (IMV) model of suicidal behaviour, one such theoretical model. We propose that defeat and entrapment drive the emergence of suicidal ideation and that a group of factors, entitled volitional moderators (VMs), govern the transition from suicidal ideation to suicidal behaviour. According to the IMV model, VMs include access to the means of suicide, exposure to suicidal behaviour, capability for suicide (fearlessness about death and increased physical pain tolerance), planning, impulsivity, mental imagery and past suicidal behaviour. In this article, we describe the theoretical origins of the IMV model, the key premises underpinning the model, empirical tests of the model and future research directions.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012734, year = {2018}, author = {Longbottom, S and Slaughter, V}, title = {Sources of children's knowledge about death and dying.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012734}, issn = {1471-2970}, abstract = {In the last century, decreases in infant and child mortality, urbanization and increases in healthcare efficacy have reduced children's personal exposure to death and dying. So how do children acquire accurate conceptions of death in this context? In this paper, we discuss three sources of children's learning about death and dying, namely, direct experience of death, parental communication about death and portrayals of death in the media and the arts. We conclude with recommendations about how best to teach modern children about this aspect of life.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012733, year = {2018}, author = {Harris, PL}, title = {Children's understanding of death: from biology to religion.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1754}, pages = {}, pmid = {30012733}, issn = {1471-2970}, abstract = {Young children construct a biological conception of death, recognizing that death terminates mental and bodily processes. Despite this recognition, many children are receptive to an alternative conception of death, which affirms that the deceased has an afterlife elsewhere. A plausible interpretation of children's receptivity to this alternative conception is that human beings, including young children, are naturally disposed to remember and keep in mind individuals to whom they are attached even when those individuals leave and are absent for extended periods. This disposition is reflected in the pervasive tendency to talk about death as a departure rather than a terminus. It also enables the living to sustain their ties to the dead, even if, in the case of death, the departure is permanent rather than temporary. Linguistic and developmental evidence for these claims is reviewed. Possible biological origins and implications for archaeological research are also discussed.This article is part of the theme issue 'Evolutionary thanatology: impacts of the dead on the living in humans and other animals'.}, } @article {pmid30012626, year = {2018}, author = {Corey, RA and Pyle, E and Allen, WJ and Watkins, DW and Casiraghi, M and Miroux, B and Arechaga, I and Politis, A and Collinson, I}, title = {Specific cardiolipin-SecY interactions are required for proton-motive force stimulation of protein secretion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7967-7972}, pmid = {30012626}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; BB/M003604/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I008675/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N015126/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 104632//Wellcome Trust/United Kingdom ; 109854/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Bacterial Secretion Systems/*chemistry/metabolism ; Escherichia coli/*chemistry/metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; *Molecular Dynamics Simulation ; *Proton-Motive Force ; SEC Translocation Channels/*chemistry/metabolism ; Thermotoga maritima/*chemistry/metabolism ; }, abstract = {The transport of proteins across or into membranes is a vital biological process, achieved in every cell by the conserved Sec machinery. In bacteria, SecYEG combines with the SecA motor protein for secretion of preproteins across the plasma membrane, powered by ATP hydrolysis and the transmembrane proton-motive force (PMF). The activities of SecYEG and SecA are modulated by membrane lipids, particularly cardiolipin (CL), a specialized phospholipid known to associate with a range of energy-transducing machines. Here, we identify two specific CL binding sites on the Thermotoga maritima SecA-SecYEG complex, through application of coarse-grained molecular dynamics simulations. We validate the computational data and demonstrate the conserved nature of the binding sites using in vitro mutagenesis, native mass spectrometry, biochemical analysis, and fluorescence spectroscopy of Escherichia coli SecYEG. The results show that the two sites account for the preponderance of functional CL binding to SecYEG, and mediate its roles in ATPase and protein transport activity. In addition, we demonstrate an important role for CL in the conferral of PMF stimulation of protein transport. The apparent transient nature of the CL interaction might facilitate proton exchange with the Sec machinery, and thereby stimulate protein transport, by a hitherto unexplored mechanism. This study demonstrates the power of coupling the high predictive ability of coarse-grained simulation with experimental analyses, toward investigation of both the nature and functional implications of protein-lipid interactions.}, } @article {pmid30012625, year = {2018}, author = {Cantor, AJ and Shah, NH and Kuriyan, J}, title = {Deep mutational analysis reveals functional trade-offs in the sequences of EGFR autophosphorylation sites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7303-E7312}, pmid = {30012625}, issn = {1091-6490}, support = {P01 AI091580/AI/NIAID NIH HHS/United States ; R01 CA096504/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {DNA Mutational Analysis ; ErbB Receptors/*chemistry/physiology ; Humans ; Phosphorylation ; Protein Conformation ; Proteome ; Signal Transduction/physiology ; }, abstract = {Upon activation, the epidermal growth factor receptor (EGFR) phosphorylates tyrosine residues in its cytoplasmic tail, which triggers the binding of Src homology 2 (SH2) and phosphotyrosine-binding (PTB) domains and initiates downstream signaling. The sequences flanking the tyrosine residues (referred to as "phosphosites") must be compatible with phosphorylation by the EGFR kinase domain and the recruitment of adapter proteins, while minimizing phosphorylation that would reduce the fidelity of signal transmission. To understand how phosphosite sequences encode these functions within a small set of residues, we carried out high-throughput mutational analysis of three phosphosite sequences in the EGFR tail. We used bacterial surface display of peptides coupled with deep sequencing to monitor phosphorylation efficiency and the binding of the SH2 and PTB domains of the adapter proteins Grb2 and Shc1, respectively. We found that the sequences of phosphosites in the EGFR tail are restricted to a subset of the range of sequences that can be phosphorylated efficiently by EGFR. Although efficient phosphorylation by EGFR can occur with either acidic or large hydrophobic residues at the -1 position with respect to the tyrosine, hydrophobic residues are generally excluded from this position in tail sequences. The mutational data suggest that this restriction results in weaker binding to adapter proteins but also disfavors phosphorylation by the cytoplasmic tyrosine kinases c-Src and c-Abl. Our results show how EGFR-family phosphosites achieve a trade-off between minimizing off-pathway phosphorylation and maintaining the ability to recruit the diverse complement of effectors required for downstream pathway activation.}, } @article {pmid30012624, year = {2018}, author = {Fei, Q and Yu, Y and Liu, L and Zhang, Y and Baldrich, P and Dai, Q and Chen, X and Meyers, BC}, title = {Biogenesis of a 22-nt microRNA in Phaseoleae species by precursor-programmed uridylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8037-8042}, pmid = {30012624}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {MicroRNAs/*biosynthesis ; *RNA Processing, Post-Transcriptional ; Soybeans/*genetics ; Uridine/*metabolism ; Uridine Monophosphate/metabolism ; }, abstract = {Phased, secondary siRNAs (phasiRNAs) represent a class of small RNAs in plants generated via distinct biogenesis pathways, predominantly dependent on the activity of 22-nt miRNAs. Most 22-nt miRNAs are processed by DCL1 from miRNA precursors containing an asymmetric bulge, yielding a 22/21-nt miRNA/miRNA* duplex. Here we show that miR1510, a soybean miRNA capable of triggering phasiRNA production from numerous nucleotide-binding leucine-rich repeat (NB-LRRs), previously described as 21 nt in its mature form, primarily accumulates as a 22-nt isoform via monouridylation. We demonstrate that, in Arabidopsis, this uridylation is performed by HESO1. Biochemical experiments showed that the 3' terminus of miR1510 is only partially 2'-O-methylated because of the terminal mispairing in the miR1510/miR1510* duplex that inhibits HEN1 activity in soybean. miR1510 emerged in the Phaseoleae ∼41-42 million years ago with a conserved precursor structure yielding a 22-nt monouridylated form, yet a variant in mung bean is processed directly in a 22-nt mature form. This analysis of miR1510 yields two observations: (i) plants can utilize postprocessing modification to generate abundant 22-nt miRNA isoforms to more efficiently regulate target mRNA abundances; and (ii) comparative analysis demonstrates an example of selective optimization of precursor processing of a young plant miRNA.}, } @article {pmid30012623, year = {2018}, author = {Prochazkova, E and Prochazkova, L and Giffin, MR and Scholte, HS and De Dreu, CKW and Kret, ME}, title = {Pupil mimicry promotes trust through the theory-of-mind network.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7265-E7274}, pmid = {30012623}, issn = {1091-6490}, mesh = {Adult ; Female ; Humans ; Magnetic Resonance Imaging ; Prefrontal Cortex/physiology ; Pupil/*physiology ; *Theory of Mind ; *Trust ; }, abstract = {The human eye can provide powerful insights into the emotions and intentions of others; however, how pupillary changes influence observers' behavior remains largely unknown. The present fMRI-pupillometry study revealed that when the pupils of interacting partners synchronously dilate, trust is promoted, which suggests that pupil mimicry affiliates people. Here we provide evidence that pupil mimicry modulates trust decisions through the activation of the theory-of-mind network (precuneus, temporo-parietal junction, superior temporal sulcus, and medial prefrontal cortex). This network was recruited during pupil-dilation mimicry compared with interactions without mimicry or compared with pupil-constriction mimicry. Furthermore, the level of theory-of-mind engagement was proportional to individual's susceptibility to pupil-dilation mimicry. These data reveal a fundamental mechanism by which an individual's pupils trigger neurophysiological responses within an observer: when interacting partners synchronously dilate their pupils, humans come to feel reflections of the inner states of others, which fosters trust formation.}, } @article {pmid30012622, year = {2018}, author = {Wolfowicz, G and Whiteley, SJ and Awschalom, DD}, title = {Electrometry by optical charge conversion of deep defects in 4H-SiC.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7879-7883}, pmid = {30012622}, issn = {1091-6490}, abstract = {Optically active point defects in various host materials, such as diamond and silicon carbide (SiC), have shown significant promise as local sensors of magnetic fields, electric fields, strain, and temperature. Modern sensing techniques take advantage of the relaxation and coherence times of the spin state within these defects. Here we show that the defect charge state can also be used to sense the environment, in particular high-frequency (megahertz to gigahertz) electric fields, complementing established spin-based techniques. This is enabled by optical charge conversion of the defects between their photoluminescent and dark charge states, with conversion rate dependent on the electric field (energy density). The technique provides an all-optical high-frequency electrometer which is tested in 4H-SiC for both ensembles of divacancies and silicon vacancies, from cryogenic to room temperature, and with a measured sensitivity of [Formula: see text] Finally, due to the piezoelectric character of SiC, we obtain spatial 3D maps of surface acoustic wave modes in a mechanical resonator.}, } @article {pmid30012621, year = {2018}, author = {Roca, J and Hori, N and Baral, S and Velmurugu, Y and Narayanan, R and Narayanan, P and Thirumalai, D and Ansari, A}, title = {Monovalent ions modulate the flux through multiple folding pathways of an RNA pseudoknot.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7313-E7322}, pmid = {30012621}, issn = {1091-6490}, mesh = {*Frameshifting, Ribosomal ; *Nucleic Acid Conformation ; RNA/*chemistry ; Sodium Chloride/pharmacology ; *Thermodynamics ; }, abstract = {The functions of RNA pseudoknots (PKs), which are minimal tertiary structural motifs and an integral part of several ribozymes and ribonucleoprotein complexes, are determined by their structure, stability, and dynamics. Therefore, it is important to elucidate the general principles governing their thermodynamics/folding mechanisms. Here, we combine laser temperature-jump experiments and coarse-grained simulations to determine the folding/unfolding pathways of VPK, a variant of the mouse mammary tumor virus (MMTV) PK involved in ribosomal frameshifting. Fluorescent nucleotide analogs (2-aminopurine and pyrrolocytidine) placed at different stem/loop positions in the PK serve as local probes allowing us to monitor the order of assembly of VPK that has two constituent hairpins with different intrinsic stabilities. We show that at 50 mM KCl, the dominant folding pathway populates only the more stable hairpin intermediate; as the salt concentration is increased, a parallel folding pathway emerges involving the less stable hairpin as an alternate intermediate. Notably, the flux between the pathways is modulated by the ionic strength. Our findings support the principle that the order of PK structure formation is determined by the relative stabilities of the hairpins, which can be altered by sequence variations or salt concentrations. The experimental results of salt effects on the partitioning between the two folding pathways are in remarkable agreement with simulations that were performed with no adjustable parameters. Our study not only unambiguously demonstrates that VPK folds by parallel pathways but also showcases the power of combining experiments and simulations for a more enriched description of RNA self-assembly.}, } @article {pmid30012620, year = {2018}, author = {Mao, D and Neumann, AR and Sun, J and Bonin, V and Mohajerani, MH and McNaughton, BL}, title = {Hippocampus-dependent emergence of spatial sequence coding in retrosplenial cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8015-8018}, pmid = {30012620}, issn = {1091-6490}, mesh = {Animals ; Female ; Hippocampus/*physiology ; Learning/*physiology ; Male ; Mice ; Mice, Transgenic ; Neocortex/*physiology ; Visual Perception/*physiology ; }, abstract = {Retrosplenial cortex (RSC) is involved in visuospatial integration and spatial learning, and RSC neurons exhibit discrete, place cell-like sequential activity that resembles the population code of space in hippocampus. To investigate the origins and population dynamics of this activity, we combined longitudinal cellular calcium imaging of dysgranular RSC neurons in mice with excitotoxic hippocampal lesions. We tracked the emergence and stability of RSC spatial activity over consecutive imaging sessions. Overall, spatial activity in RSC was experience-dependent, emerging gradually over time, but, as seen in the hippocampus, the spatial code changed dynamically across days. Bilateral but not unilateral hippocampal lesions impeded the development of spatial activity in RSC. Thus, the emergence of spatial activity in RSC, a major recipient of hippocampal information, depends critically on an intact hippocampus; the indirect connections between the dysgranular RSC and the hippocampus further indicate that hippocampus may exert such influences polysynaptically within neocortex.}, } @article {pmid30012619, year = {2018}, author = {Cowton, TR and Sole, AJ and Nienow, PW and Slater, DA and Christoffersen, P}, title = {Linear response of east Greenland's tidewater glaciers to ocean/atmosphere warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7907-7912}, pmid = {30012619}, issn = {1091-6490}, abstract = {Predicting the retreat of tidewater outlet glaciers forms a major obstacle to forecasting the rate of mass loss from the Greenland Ice Sheet. This reflects the challenges of modeling the highly dynamic, topographically complex, and data-poor environment of the glacier-fjord systems that link the ice sheet to the ocean. To avoid these difficulties, we investigate the extent to which tidewater glacier retreat can be explained by simple variables: air temperature, meltwater runoff, ocean temperature, and two simple parameterizations of "ocean/atmosphere" forcing based on the combined influence of runoff and ocean temperature. Over a 20-y period at 10 large tidewater outlet glaciers along the east coast of Greenland, we find that ocean/atmosphere forcing can explain up to 76% of the variability in terminus position at individual glaciers and 54% of variation in terminus position across all 10 glaciers. Our findings indicate that (i) the retreat of east Greenland's tidewater glaciers is best explained as a product of both oceanic and atmospheric warming and (ii) despite the complexity of tidewater glacier behavior, over multiyear timescales a significant proportion of terminus position change can be explained as a simple function of this forcing. These findings thus demonstrate that simple parameterizations can play an important role in predicting the response of the ice sheet to future climate warming.}, } @article {pmid30012618, year = {2018}, author = {Shkolnik, D and Nuriel, R and Bonza, MC and Costa, A and Fromm, H}, title = {MIZ1 regulates ECA1 to generate a slow, long-distance phloem-transmitted Ca2+ signal essential for root water tracking in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8031-8036}, pmid = {30012618}, issn = {1091-6490}, mesh = {Adaptor Proteins, Vesicular Transport/*physiology ; Arabidopsis/*metabolism ; Arabidopsis Proteins/*physiology ; Calcium/metabolism ; Calcium Signaling/*physiology ; Cytosol/metabolism ; Phloem/*metabolism ; Plant Roots/*metabolism ; Water/*metabolism ; }, abstract = {Ever since Darwin postulated that the tip of the root is sensitive to moisture differences and that it "transmits an influence to the upper adjoining part, which bends towards the source of moisture" [Darwin C, Darwin F (1880) The Power of Movement in Plants, pp 572-574], the signal underlying this tropic response has remained elusive. Using the FRET-based Cameleon Ca2+ sensor in planta, we show that a water potential gradient applied across the root tip generates a slow, long-distance asymmetric cytosolic Ca2+ signal in the phloem, which peaks at the elongation zone, where it is dispersed laterally and asymmetrically to peripheral cells, where cell elongation occurs. In addition, the MIZ1 protein, whose biochemical function is unknown but is required for root curvature toward water, is indispensable for generating the slow, long-distance Ca2+ signal. Furthermore, biochemical and genetic manipulations that elevate cytosolic Ca2+ levels, including mutants of the endoplasmic reticulum (ER) Ca2+-ATPase isoform ECA1, enhance root curvature toward water. Finally, coimmunoprecipitation of plant proteins and functional complementation assays in yeast cells revealed that MIZ1 directly binds to ECA1 and inhibits its activity. We suggest that the inhibition of ECA1 by MIZ1 changes the balance between cytosolic Ca2+ influx and efflux and generates the cytosolic Ca2+ signal required for water tracking.}, } @article {pmid30012617, year = {2018}, author = {Zhang, W and Lu, Y and van der Werf, W and Huang, J and Wu, F and Zhou, K and Deng, X and Jiang, Y and Wu, K and Rosegrant, MW}, title = {Multidecadal, county-level analysis of the effects of land use, Bt cotton, and weather on cotton pests in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7700-E7709}, pmid = {30012617}, issn = {1091-6490}, mesh = {*Agriculture ; Animals ; Aphids ; Bacillus thuringiensis/*genetics ; Gossypium/*genetics ; Insecticides/pharmacology ; Moths ; Pest Control, Biological/*methods ; *Weather ; }, abstract = {Long-term changes in land use, climate, and agricultural technologies may affect pest severity and management. The influences of these major drivers can only be identified by analyzing long-term data. This study examines panel data on land use, adoption of genetically modified Bacillus thuringiensis (Bt) insect-resistant cotton, weather, pest severity, and insecticide use on three major cotton pests for 51 counties in China during 1991-2015. Bt cotton had pervasive effects on the whole pest complex in cotton and its management. Adoption resulted in major reductions in insecticide use for bollworm control. The resulting restoration of aphid biological control decreased aphid severity. However, mirid bugs, which have few effective natural enemies in cotton, increased in severity with warming May and reduced insecticide spraying against bollworm. The effects of landscape on pest severity were pest specific. The severity of cotton aphid and mirid bugs decreased with higher land use diversity, but the severity of highly polyphagous cotton bollworm was unrelated to land use diversity. Shares of forest, water body, and unused land area were negatively associated with the severity of mirid bugs, whereas cotton bollworm responded positively to the shares of water body and unused land area. Farmers sprayed insecticides at mild infestation levels and responded aggressively to severe bollworm outbreaks. Findings support the usefulness of Bt-based plant resistance as a component of integrated pest management (IPM) but highlight the potential for unexpected outcomes resulting from agro-ecosystem feedback loops as well as the importance of climate.}, } @article {pmid30012616, year = {2018}, author = {Lin, X and Noel, JK and Wang, Q and Ma, J and Onuchic, JN}, title = {Atomistic simulations indicate the functional loop-to-coiled-coil transition in influenza hemagglutinin is not downhill.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {E7905-E7913}, pmid = {30012616}, issn = {1091-6490}, support = {R01 GM116280/GM/NIGMS NIH HHS/United States ; R01 GM127628/GM/NIGMS NIH HHS/United States ; R01 GM110310/GM/NIGMS NIH HHS/United States ; R01 AI067839/AI/NIAID NIH HHS/United States ; R01 GM067801/GM/NIGMS NIH HHS/United States ; R01 GM116961/GM/NIGMS NIH HHS/United States ; }, mesh = {Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/metabolism ; Influenza A virus/*chemistry/metabolism ; *Molecular Dynamics Simulation ; Protein Structure, Quaternary ; Protein Structure, Secondary ; }, abstract = {Influenza hemagglutinin (HA) mediates viral entry into host cells through a large-scale conformational rearrangement at low pH that leads to fusion of the viral and endosomal membranes. Crystallographic and biochemical data suggest that a loop-to-coiled-coil transition of the B-loop region of HA is important for driving this structural rearrangement. However, the microscopic picture for this proposed "spring-loaded" movement is missing. In this study, we focus on understanding the transition of the B loop and perform a set of all-atom molecular dynamics simulations of the full B-loop trimeric structure with the CHARMM36 force field. The free-energy profile constructed from our simulations describes a B loop that stably folds half of the postfusion coiled coil in tens of microseconds, but the full coiled coil is unfavorable. A buried hydrophilic residue, Thr59, is implicated in destabilizing the coiled coil. Interestingly, this conserved threonine is the only residue in the B loop that strictly differentiates between the group 1 and 2 HA molecules. Microsecond-scale constant temperature simulations revealed that kinetic traps in the structural switch of the B loop can be caused by nonnative, intramonomer, or intermonomer β-sheets. The addition of the A helix stabilized the postfusion state of the B loop, but introduced the possibility for further β-sheet structures. Overall, our results do not support a description of the B loop in group 2 HAs as a stiff spring, but, rather, it allows for more structural heterogeneity in the placement of the fusion peptides during the fusion process.}, } @article {pmid30012615, year = {2018}, author = {Hechtman, LA and Moore, NP and Schulkey, CE and Miklos, AC and Calcagno, AM and Aragon, R and Greenberg, JH}, title = {NIH funding longevity by gender.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7943-7948}, pmid = {30012615}, issn = {1091-6490}, mesh = {Biomedical Research/*economics ; Female ; Financing, Organized/*economics ; Humans ; *Longevity ; Male ; *National Institutes of Health (U.S.) ; United States ; *Women ; }, abstract = {Women have achieved parity with men among biomedical science degree holders but remain underrepresented in academic positions. The National Institutes of Health (NIH)-the world's largest public funder of biomedical research-receives less than one-third of its new grant applications from women. Correspondingly, women compose less than one-third of NIH research grantees, even though they are as successful as men in obtaining first-time grants. Our study examined women's and men's NIH funding trajectories over time (n = 34,770), exploring whether women remain funded at the same rate as men after receiving their first major research grants. A survival analysis demonstrated a slightly lower funding longevity for women. We next examined gender differences in application, review, and funding outcomes. Women individually held fewer grants, submitted fewer applications, and were less successful in renewing grants-factors that could lead to gender differences in funding longevity. Finally, two adjusted survival models that account for initial investigator characteristics or subsequent application behavior showed no gender differences, suggesting that the small observed longevity differences are affected by both sets of factors. Overall, given men's and women's generally comparable funding longevities, the data contradict the common assumption that women experience accelerated attrition compared with men across all career stages. Women's likelihood of sustaining NIH funding may be better than commonly perceived. This suggests a need to explore women's underrepresentation among initial NIH grantees, as well as their lower rates of new and renewal application submissions.}, } @article {pmid30012614, year = {2018}, author = {Arranz-Otaegui, A and Gonzalez Carretero, L and Ramsey, MN and Fuller, DQ and Richter, T}, title = {Archaeobotanical evidence reveals the origins of bread 14,400 years ago in northeastern Jordan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7925-7930}, pmid = {30012614}, issn = {1091-6490}, mesh = {Bread/*history ; Crops, Agricultural/*history ; *Cyperaceae ; History, Ancient ; Jordan ; *Plant Tubers ; *Triticum ; }, abstract = {The origins of bread have long been associated with the emergence of agriculture and cereal domestication during the Neolithic in southwest Asia. In this study we analyze a total of 24 charred food remains from Shubayqa 1, a Natufian hunter-gatherer site located in northeastern Jordan and dated to 14.6-11.6 ka cal BP. Our finds provide empirical data to demonstrate that the preparation and consumption of bread-like products predated the emergence of agriculture by at least 4,000 years. The interdisciplinary analyses indicate the use of some of the "founder crops" of southwest Asian agriculture (e.g., Triticum boeoticum, wild einkorn) and root foods (e.g., Bolboschoenus glaucus, club-rush tubers) to produce flat bread-like products. The available archaeobotanical evidence for the Natufian period indicates that cereal exploitation was not common during this time, and it is most likely that cereal-based meals like bread become staples only when agriculture was firmly established.}, } @article {pmid30012613, year = {2018}, author = {Gao, P and Ho, PL and Yan, B and Sze, KH and Davies, J and Kao, RYT}, title = {Suppression of Staphylococcus aureus virulence by a small-molecule compound.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8003-8008}, pmid = {30012613}, issn = {1091-6490}, mesh = {Animals ; Anti-Bacterial Agents/chemistry/*pharmacology ; Bacterial Proteins/*antagonists & inhibitors/metabolism ; Disease Models, Animal ; Endopeptidase Clp/*antagonists & inhibitors/metabolism ; Mice ; *Promoter Regions, Genetic ; Staphylococcal Infections/*drug therapy/genetics/metabolism/pathology ; Staphylococcus aureus/genetics/*metabolism/*pathogenicity ; }, abstract = {Emerging antibiotic resistance among bacterial pathogens has necessitated the development of alternative approaches to combat drug-resistance-associated infection. The abolition of Staphylococcus aureus virulence by targeting multiple-virulence gene products represents a promising strategy for exploration. A multiplex promoter reporter platform using gfp-luxABCDE dual-reporter plasmids with selected promoters from S. aureus-virulence-associated genes was used to identify compounds that modulate the expression of virulence factors. One small-molecule compound, M21, was identified from a chemical library to reverse virulent S. aureus into its nonvirulent state. M21 is a noncompetitive inhibitor of ClpP and alters α-toxin expression in a ClpP-dependent manner. A mouse model of infection indicated that M21 could attenuate S. aureus virulence. This nonantibiotic compound has been shown to suppress the expression of multiple unrelated virulence factors in S. aureus, suggesting that targeting a master regulator of virulence is an effective way to control virulence. Our results illustrate the power of chemical genetics in the modulation of virulence gene expression in pathogenic bacteria.}, } @article {pmid30012612, year = {2018}, author = {Jimenez-Vargas, NN and Pattison, LA and Zhao, P and Lieu, T and Latorre, R and Jensen, DD and Castro, J and Aurelio, L and Le, GT and Flynn, B and Herenbrink, CK and Yeatman, HR and Edgington-Mitchell, L and Porter, CJH and Halls, ML and Canals, M and Veldhuis, NA and Poole, DP and McLean, P and Hicks, GA and Scheff, N and Chen, E and Bhattacharya, A and Schmidt, BL and Brierley, SM and Vanner, SJ and Bunnett, NW}, title = {Protease-activated receptor-2 in endosomes signals persistent pain of irritable bowel syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7438-E7447}, pmid = {30012612}, issn = {1091-6490}, support = {R01 DE025393/DE/NIDCR NIH HHS/United States ; R01 DE026806/DE/NIDCR NIH HHS/United States ; R01 NS102722/NS/NINDS NIH HHS/United States ; R56 DE025393/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Chronic Pain/*etiology ; Endocytosis ; Endosomes/*physiology ; Extracellular Signal-Regulated MAP Kinases/physiology ; Humans ; Irritable Bowel Syndrome/*physiopathology ; Nociception ; Nociceptors/physiology ; Receptor, PAR-2/*physiology ; Signal Transduction/*physiology ; Trypsin/pharmacology ; }, abstract = {Once activated at the surface of cells, G protein-coupled receptors (GPCRs) redistribute to endosomes, where they can continue to signal. Whether GPCRs in endosomes generate signals that contribute to human disease is unknown. We evaluated endosomal signaling of protease-activated receptor-2 (PAR2), which has been proposed to mediate pain in patients with irritable bowel syndrome (IBS). Trypsin, elastase, and cathepsin S, which are activated in the colonic mucosa of patients with IBS and in experimental animals with colitis, caused persistent PAR2-dependent hyperexcitability of nociceptors, sensitization of colonic afferent neurons to mechanical stimuli, and somatic mechanical allodynia. Inhibitors of clathrin- and dynamin-dependent endocytosis and of mitogen-activated protein kinase kinase-1 prevented trypsin-induced hyperexcitability, sensitization, and allodynia. However, they did not affect elastase- or cathepsin S-induced hyperexcitability, sensitization, or allodynia. Trypsin stimulated endocytosis of PAR2, which signaled from endosomes to activate extracellular signal-regulated kinase. Elastase and cathepsin S did not stimulate endocytosis of PAR2, which signaled from the plasma membrane to activate adenylyl cyclase. Biopsies of colonic mucosa from IBS patients released proteases that induced persistent PAR2-dependent hyperexcitability of nociceptors, and PAR2 association with β-arrestins, which mediate endocytosis. Conjugation to cholestanol promoted delivery and retention of antagonists in endosomes containing PAR2 A cholestanol-conjugated PAR2 antagonist prevented persistent trypsin- and IBS protease-induced hyperexcitability of nociceptors. The results reveal that PAR2 signaling from endosomes underlies the persistent hyperexcitability of nociceptors that mediates chronic pain of IBS. Endosomally targeted PAR2 antagonists are potential therapies for IBS pain. GPCRs in endosomes transmit signals that contribute to human diseases.}, } @article {pmid30012611, year = {2018}, author = {McClure, CD and Jaffe, DA}, title = {US particulate matter air quality improves except in wildfire-prone areas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7901-7906}, pmid = {30012611}, issn = {1091-6490}, mesh = {Air Pollutants/*analysis ; *Air Pollution ; Particulate Matter/*analysis ; United States ; }, abstract = {Using data from rural monitoring sites across the contiguous United States, we evaluated fine particulate matter (PM2.5) trends for 1988-2016. We calculate trends in the policy-relevant 98th quantile of PM2.5 using Quantile Regression. We use Kriging and Gaussian Geostatistical Simulations to interpolate trends between observed data points. Overall, we found positive trends in 98th quantile PM2.5 at sites within the Northwest United States (average 0.21 ± 0.12 µg·m-3·y-1; ±95% confidence interval). This was in contrast with sites throughout the rest of country, which showed a negative trend in 98th quantile PM2.5, likely due to reductions in anthropogenic emissions (average -0.66 ± 0.10 µg·m-3·y-1). The positive trend in 98th quantile PM2.5 is due to wildfire activity and was supported by positive trends in total carbon and no trend in sulfate across the Northwest. We also evaluated daily moderate resolution imaging spectroradiometer (MODIS) aerosol optical depth (AOD) for 2002-2017 throughout the United States to compare with ground-based trends. For both Interagency Monitoring of Protected Visual Environments (IMPROVE) PM2.5 and MODIS AOD datasets, we found positive 98th quantile trends in the Northwest (1.77 ± 0.68% and 2.12 ± 0.81% per year, respectively) through 2016. The trend in Northwest AOD is even greater if data for the high-fire year of 2017 are included. These results indicate a decrease in PM2.5 over most of the country but a positive trend in the 98th quantile PM2.5 across the Northwest due to wildfires.}, } @article {pmid30012610, year = {2018}, author = {Miton, CM and Jonas, S and Fischer, G and Duarte, F and Mohamed, MF and van Loo, B and Kintses, B and Kamerlin, SCL and Tokuriki, N and Hyvönen, M and Hollfelder, F}, title = {Evolutionary repurposing of a sulfatase: A new Michaelis complex leads to efficient transition state charge offset.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7293-E7302}, pmid = {30012610}, issn = {1091-6490}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arylsulfatases/*chemistry ; Catalysis ; Catalytic Domain ; *Directed Molecular Evolution ; Hydrolysis ; Organophosphorus Compounds/chemistry ; Protein Conformation ; }, abstract = {The recruitment and evolutionary optimization of promiscuous enzymes is key to the rapid adaptation of organisms to changing environments. Our understanding of the precise mechanisms underlying enzyme repurposing is, however, limited: What are the active-site features that enable the molecular recognition of multiple substrates with contrasting catalytic requirements? To gain insights into the molecular determinants of adaptation in promiscuous enzymes, we performed the laboratory evolution of an arylsulfatase to improve its initially weak phenylphosphonate hydrolase activity. The evolutionary trajectory led to a 100,000-fold enhancement of phenylphosphonate hydrolysis, while the native sulfate and promiscuous phosphate mono- and diester hydrolyses were only marginally affected (≤50-fold). Structural, kinetic, and in silico characterizations of the evolutionary intermediates revealed that two key mutations, T50A and M72V, locally reshaped the active site, improving access to the catalytic machinery for the phosphonate. Measured transition state (TS) charge changes along the trajectory suggest the creation of a new Michaelis complex (E•S, enzyme-substrate), with enhanced leaving group stabilization in the TS for the promiscuous phosphonate (βleavinggroup from -1.08 to -0.42). Rather than altering the catalytic machinery, evolutionary repurposing was achieved by fine-tuning the molecular recognition of the phosphonate in the Michaelis complex, and by extension, also in the TS. This molecular scenario constitutes a mechanistic alternative to adaptation solely based on enzyme flexibility and conformational selection. Instead, rapid functional transitions between distinct chemical reactions rely on the high reactivity of permissive active-site architectures that allow multiple substrate binding modes.}, } @article {pmid30012609, year = {2018}, author = {Chandran Suja, V and Kar, A and Cates, W and Remmert, SM and Savage, PD and Fuller, GG}, title = {Evaporation-induced foam stabilization in lubricating oils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7919-7924}, pmid = {30012609}, issn = {1091-6490}, abstract = {Foaming in liquids is ubiquitous in nature. Whereas the mechanism of foaming in aqueous systems has been thoroughly studied, nonaqueous systems have not enjoyed the same level of examination. Here we study the mechanism of foaming in a widely used class of nonaqueous liquids: lubricant base oils. Using a newly developed experimental technique, we show that the stability of lubricant foams can be evaluated at the level of single bubbles. The results obtained with this single-bubble technique indicate that solutocapillary flows are central to lubricant foam stabilization. These solutocapillary flows are shown to originate from the differential evaporation of multicomponent lubricants-an unexpected result given the low volatility of nonaqueous liquids. Further, we show that mixing of some combinations of different lubricant base oils, a common practice in the industry, exacerbates solutocapillary flows and hence leads to increased foaming.}, } @article {pmid30012608, year = {2018}, author = {Sathyanarayana, P and Maurya, S and Behera, A and Ravichandran, M and Visweswariah, SS and Ayappa, KG and Roy, R}, title = {Cholesterol promotes Cytolysin A activity by stabilizing the intermediates during pore formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7323-E7330}, pmid = {30012608}, issn = {1091-6490}, mesh = {Cell Membrane/drug effects ; Cholesterol/*chemistry ; Escherichia coli Proteins/chemistry/*toxicity ; Hemolysin Proteins/chemistry/*toxicity ; Lipid Bilayers/chemistry ; Molecular Dynamics Simulation ; Protein Multimerization ; }, abstract = {Pore-forming toxins (PFTs) form nanoscale pores across target membranes causing cell death. Cytolysin A (ClyA) from Escherichia coli is a prototypical α-helical toxin that contributes to cytolytic phenotype of several pathogenic strains. It is produced as a monomer and, upon membrane exposure, undergoes conformational changes and finally oligomerizes to form a dodecameric pore, thereby causing ion imbalance and finally cell death. However, our current understanding of this assembly process is limited to studies in detergents, which do not capture the physicochemical properties of biological membranes. Here, using single-molecule imaging and molecular dynamics simulations, we study the ClyA assembly pathway on phospholipid bilayers. We report that cholesterol stimulates pore formation, not by enhancing initial ClyA binding to the membrane but by selectively stabilizing a protomer-like conformation. This was mediated by specific interactions by cholesterol-interacting residues in the N-terminal helix. Additionally, cholesterol stabilized the oligomeric structure using bridging interactions in the protomer-protomer interfaces, thereby resulting in enhanced ClyA oligomerization. This dual stabilization of distinct intermediates by cholesterol suggests a possible molecular mechanism by which ClyA achieves selective membrane rupture of eukaryotic cell membranes. Topological similarity to eukaryotic membrane proteins suggests evolution of a bacterial α-toxin to adopt eukaryotic motifs for its activation. Broad mechanistic correspondence between pore-forming toxins hints at a wider prevalence of similar protein membrane insertion mechanisms.}, } @article {pmid30012607, year = {2018}, author = {Elmenhorst, EM and Elmenhorst, D and Benderoth, S and Kroll, T and Bauer, A and Aeschbach, D}, title = {Cognitive impairments by alcohol and sleep deprivation indicate trait characteristics and a potential role for adenosine A1 receptors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8009-8014}, pmid = {30012607}, issn = {1091-6490}, mesh = {Adult ; *Alcohol Drinking/genetics/metabolism ; *Brain/diagnostic imaging/metabolism ; *Cognitive Dysfunction/diagnostic imaging/genetics/metabolism ; Humans ; Male ; *Positron-Emission Tomography ; *Quantitative Trait, Heritable ; *Receptor, Adenosine A1/genetics/metabolism ; *Sleep Deprivation/diagnostic imaging/genetics/metabolism ; }, abstract = {Trait-like differences in cognitive performance after sleep loss put some individuals more at risk than others, the basis of such disparities remaining largely unknown. Similarly, interindividual differences in impairment in response to alcohol intake have been observed. We tested whether performance impairments due to either acute or chronic sleep loss can be predicted by an individual's vulnerability to acute alcohol intake. Also, we used positron emission tomography (PET) to test whether acute alcohol infusion results in an up-regulation of cerebral A1 adenosine receptors (A1ARs), similar to the changes previously observed following sleep deprivation. Sustained attention in the psychomotor vigilance task (PVT) was tested in 49 healthy volunteers (26 ± 5 SD years; 15 females) (i) under baseline conditions: (ii) after ethanol intake, and after either (iii) total sleep deprivation (TSD; 35 hours awake; n = 35) or (iv) partial sleep deprivation (PSD; four nights with 5 hours scheduled sleep; n = 14). Ethanol- versus placebo-induced changes in cerebral A1AR availability were measured in 10 healthy male volunteers (31 ± 9 years) with [18F]8-cyclopentyl-3-(3-fluoropropyl)-1-propylxanthine (CPFPX) PET. Highly significant correlations between the performance impairments induced by ethanol and sleep deprivation were found for various PVT parameters, including mean speed (TSD, r = 0.62; PSD, r = 0.84). A1AR availability increased up to 26% in several brain regions with ethanol infusion. Our studies revealed individual trait characteristics for being either vulnerable or resilient to both alcohol and to sleep deprivation. Both interventions induce gradual increases in cerebral A1AR availability, pointing to a potential common molecular response mechanism.}, } @article {pmid30012606, year = {2018}, author = {Yang, W and Liu, Q and Gao, Z and Yue, Z and Xu, B}, title = {Theoretical search for heterogeneously architected 2D structures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7245-E7254}, pmid = {30012606}, issn = {1091-6490}, abstract = {Architected 2D structures are of growing interest due to their unique mechanical and physical properties for applications in stretchable electronics, controllable phononic/photonic modulators, and switchable optical/electrical devices; however, the underpinning theory of understanding their elastic properties and enabling principles in search of emerging structures with well-defined arrangements and/or bonding connections of assembled elements has yet to be established. Here, we present two theoretical frameworks in mechanics-strain energy-based theory and displacement continuity-based theory-to predict the elastic properties of 2D structures and demonstrate their application in a search for novel architected 2D structures that are composed of heterogeneously arranged, arbitrarily shaped lattice cell structures with regulatory adjacent bonding connections of cells, referred to as heterogeneously architected 2D structures (HASs). By patterning lattice cell structures and tailoring their connections, the elastic properties of HASs can span a very broad range from nearly zero to beyond those of individual lattice cells by orders of magnitude. Interface indices that represent both the pattern arrangements of basic lattice cells and local bonding disconnections in HASs are also proposed and incorporated to intelligently design HASs with on-demand Young's modulus and geometric features. This study offers a theoretical foundation toward future architected structures by design with unprecedented properties and functions.}, } @article {pmid30012605, year = {2018}, author = {Zorba, A and Nguyen, C and Xu, Y and Starr, J and Borzilleri, K and Smith, J and Zhu, H and Farley, KA and Ding, W and Schiemer, J and Feng, X and Chang, JS and Uccello, DP and Young, JA and Garcia-Irrizary, CN and Czabaniuk, L and Schuff, B and Oliver, R and Montgomery, J and Hayward, MM and Coe, J and Chen, J and Niosi, M and Luthra, S and Shah, JC and El-Kattan, A and Qiu, X and West, GM and Noe, MC and Shanmugasundaram, V and Gilbert, AM and Brown, MF and Calabrese, MF}, title = {Delineating the role of cooperativity in the design of potent PROTACs for BTK.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7285-E7292}, pmid = {30012605}, issn = {1091-6490}, mesh = {Agammaglobulinaemia Tyrosine Kinase ; Animals ; Cells, Cultured ; Ligands ; Polyubiquitin/metabolism ; Protein-Tyrosine Kinases/*metabolism ; *Proteolysis ; Rats ; Thermodynamics ; Ubiquitin-Protein Ligases/*metabolism ; *Ubiquitination ; }, abstract = {Proteolysis targeting chimeras (PROTACs) are heterobifunctional small molecules that simultaneously bind to a target protein and an E3 ligase, thereby leading to ubiquitination and subsequent degradation of the target. They present an exciting opportunity to modulate proteins in a manner independent of enzymatic or signaling activity. As such, they have recently emerged as an attractive mechanism to explore previously "undruggable" targets. Despite this interest, fundamental questions remain regarding the parameters most critical for achieving potency and selectivity. Here we employ a series of biochemical and cellular techniques to investigate requirements for efficient knockdown of Bruton's tyrosine kinase (BTK), a nonreceptor tyrosine kinase essential for B cell maturation. Members of an 11-compound PROTAC library were investigated for their ability to form binary and ternary complexes with BTK and cereblon (CRBN, an E3 ligase component). Results were extended to measure effects on BTK-CRBN cooperative interactions as well as in vitro and in vivo BTK degradation. Our data show that alleviation of steric clashes between BTK and CRBN by modulating PROTAC linker length within this chemical series allows potent BTK degradation in the absence of thermodynamic cooperativity.}, } @article {pmid30012604, year = {2018}, author = {Kanner, S and Goldin, M and Galron, R and Ben Jacob, E and Bonifazi, P and Barzilai, A}, title = {Astrocytes restore connectivity and synchronization in dysfunctional cerebellar networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8025-8030}, pmid = {30012604}, issn = {1091-6490}, mesh = {Animals ; Astrocytes/*physiology ; Ataxia Telangiectasia Mutated Proteins/genetics/physiology ; Autophagy ; Cells, Cultured ; Cerebellar Diseases/*physiopathology ; Mice ; Nerve Net/*physiopathology ; Synapses/physiology ; }, abstract = {Evidence suggests that astrocytes play key roles in structural and functional organization of neuronal circuits. To understand how astrocytes influence the physiopathology of cerebellar circuits, we cultured cells from cerebella of mice that lack the ATM gene. Mutations in ATM are causative of the human cerebellar degenerative disease ataxia-telangiectasia. Cerebellar cultures grown from Atm-/- mice had disrupted network synchronization, atrophied astrocytic arborizations, reduced autophagy levels, and higher numbers of synapses per neuron than wild-type cultures. Chimeric circuitries composed of wild-type astrocytes and Atm-/- neurons were indistinguishable from wild-type cultures. Adult cerebellar characterizations confirmed disrupted astrocyte morphology, increased GABAergic synaptic markers, and reduced autophagy in Atm-/- compared with wild-type mice. These results indicate that astrocytes can impact neuronal circuits at levels ranging from synaptic expression to global dynamics.}, } @article {pmid30012603, year = {2018}, author = {Kaplan, E and Greene, NP and Crow, A and Koronakis, V}, title = {Insights into bacterial lipoprotein trafficking from a structure of LolA bound to the LolC periplasmic domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7389-E7397}, pmid = {30012603}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MR/N000994/1//Medical Research Council/United Kingdom ; 101828/Z/13/Z//Wellcome Trust/United Kingdom ; }, mesh = {ATP-Binding Cassette Transporters/chemistry/*metabolism ; Adenosine Triphosphate/chemistry ; Escherichia coli Proteins/chemistry/*metabolism ; Hydrolysis ; Models, Molecular ; Periplasm/*metabolism ; Periplasmic Binding Proteins/chemistry/*metabolism ; Protein Interaction Mapping ; Protein Transport ; }, abstract = {In Gram-negative bacteria, outer-membrane lipoproteins are essential for maintaining cellular integrity, transporting nutrients, establishing infections, and promoting the formation of biofilms. The LolCDE ABC transporter, LolA chaperone, and LolB outer-membrane receptor form an essential system for transporting newly matured lipoproteins from the outer leaflet of the cytoplasmic membrane to the innermost leaflet of the outer membrane. Here, we present a crystal structure of LolA in complex with the periplasmic domain of LolC. The structure reveals how a solvent-exposed β-hairpin loop (termed the "Hook") and trio of surface residues (the "Pad") of LolC are essential for recruiting LolA from the periplasm and priming it to receive lipoproteins. Experiments with purified LolCDE complex demonstrate that association with LolA is independent of nucleotide binding and hydrolysis, and homology models based on the MacB ABC transporter predict that LolA recruitment takes place at a periplasmic site located at least 50 Å from the inner membrane. Implications for the mechanism of lipoprotein extraction and transfer are discussed. The LolA-LolC structure provides atomic details on a key protein interaction within the Lol pathway and constitutes a vital step toward the complete molecular understanding of this important system.}, } @article {pmid30012602, year = {2018}, author = {Patel, D and Roy, A and Kundu, M and Jana, M and Luan, CH and Gonzalez, FJ and Pahan, K}, title = {Aspirin binds to PPARα to stimulate hippocampal plasticity and protect memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7408-E7417}, pmid = {30012602}, issn = {1091-6490}, support = {I01 BX002174/BX/BLRD VA/United States ; R01 AG050431/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Aspirin/metabolism/*pharmacology ; Cyclic AMP Response Element-Binding Protein/genetics ; Hippocampus/*drug effects/physiology ; Memory/*drug effects ; Mice ; Mice, Inbred C57BL ; Neuronal Plasticity/*drug effects/physiology ; PPAR alpha/*metabolism ; Synapses/drug effects/physiology ; }, abstract = {Despite its long history, until now, no receptor has been identified for aspirin, one of the most widely used medicines worldwide. Here we report that peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor involved in fatty acid metabolism, serves as a receptor of aspirin. Detailed proteomic analyses including cheminformatics, thermal shift assays, and TR-FRET revealed that aspirin, but not other structural homologs, acts as a PPARα ligand through direct binding at the Tyr314 residue of the PPARα ligand-binding domain. On binding to PPARα, aspirin stimulated hippocampal plasticity via transcriptional activation of cAMP response element-binding protein (CREB). Finally, hippocampus-dependent behavioral analyses, calcium influx assays in hippocampal slices and quantification of dendritic spines demonstrated that low-dose aspirin treatment improved hippocampal plasticity and memory in FAD5X mice, but not in FAD5X/Ppara-null mice. These findings highlight a property of aspirin: stimulating hippocampal plasticity via direct interaction with PPARα.}, } @article {pmid30012601, year = {2018}, author = {Harris, JD and Moran, MJ and Aprahamian, I}, title = {New molecular switch architectures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9414-9422}, pmid = {30012601}, issn = {1091-6490}, abstract = {In this paper we elaborate on recently developed molecular switch architectures and how these new systems can help with the realization of new functions and advancement of artificial molecular machines. Progress in chemically and photoinduced switches and motors is summarized and contextualized such that the reader may gain an appreciation for the novel tools that have come about in the past decade. Many of these systems offer distinct advantages over commonly employed switches, including improved fidelity, addressability, and robustness. Thus, this paper serves as a jumping-off point for researchers seeking new switching motifs for specific applications, or ones that address the limitations of presently available systems.}, } @article {pmid30012600, year = {2018}, author = {Taubert, J and Flessert, M and Wardle, SG and Basile, BM and Murphy, AP and Murray, EA and Ungerleider, LG}, title = {Amygdala lesions eliminate viewing preferences for faces in rhesus monkeys.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8043-8048}, pmid = {30012600}, issn = {1091-6490}, support = {ZIA MH002918/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/*physiology ; Animals ; Eye Movements ; Face ; Female ; Macaca mulatta ; Male ; *Pattern Recognition, Visual ; *Visual Perception ; }, abstract = {In free-viewing experiments, primates orient preferentially toward faces and face-like stimuli. To investigate the neural basis of this behavior, we measured the spontaneous viewing preferences of monkeys with selective bilateral amygdala lesions. The results revealed that when faces and nonface objects were presented simultaneously, monkeys with amygdala lesions had no viewing preference for either conspecific faces or illusory facial features in everyday objects. Instead of directing eye movements toward socially relevant features in natural images, we found that, after amygdala loss, monkeys are biased toward features with increased low-level salience. We conclude that the amygdala has a role in our earliest specialized response to faces, a behavior thought to be a precursor for efficient social communication and essential for the development of face-selective cortex.}, } @article {pmid30012599, year = {2018}, author = {Miehlbradt, J and Cherpillod, A and Mintchev, S and Coscia, M and Artoni, F and Floreano, D and Micera, S}, title = {Data-driven body-machine interface for the accurate control of drones.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7913-7918}, pmid = {30012599}, issn = {1091-6490}, abstract = {The accurate teleoperation of robotic devices requires simple, yet intuitive and reliable control interfaces. However, current human-machine interfaces (HMIs) often fail to fulfill these characteristics, leading to systems requiring an intensive practice to reach a sufficient operation expertise. Here, we present a systematic methodology to identify the spontaneous gesture-based interaction strategies of naive individuals with a distant device, and to exploit this information to develop a data-driven body-machine interface (BoMI) to efficiently control this device. We applied this approach to the specific case of drone steering and derived a simple control method relying on upper-body motion. The identified BoMI allowed participants with no prior experience to rapidly master the control of both simulated and real drones, outperforming joystick users, and comparing with the control ability reached by participants using the bird-like flight simulator Birdly.}, } @article {pmid30012598, year = {2018}, author = {Lucquin, A and Robson, HK and Eley, Y and Shoda, S and Veltcheva, D and Gibbs, K and Heron, CP and Isaksson, S and Nishida, Y and Taniguchi, Y and Nakajima, S and Kobayashi, K and Jordan, P and Kaner, S and Craig, OE}, title = {The impact of environmental change on the use of early pottery by East Asian hunter-gatherers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7931-7936}, pmid = {30012598}, issn = {1091-6490}, mesh = {*Archaeology ; Climate Change/*history ; Far East ; History, Ancient ; Humans ; }, abstract = {The invention of pottery was a fundamental technological advancement with far-reaching economic and cultural consequences. Pottery containers first emerged in East Asia during the Late Pleistocene in a wide range of environmental settings, but became particularly prominent and much more widely dispersed after climatic warming at the start of the Holocene. Some archaeologists argue that this increasing usage was driven by environmental factors, as warmer climates would have generated a wider range of terrestrial plant and animal resources that required processing in pottery. However, this hypothesis has never been directly tested. Here, in one of the largest studies of its kind, we conducted organic residue analysis of >800 pottery vessels selected from 46 Late Pleistocene and Early Holocene sites located across the Japanese archipelago to identify their contents. Our results demonstrate that pottery had a strong association with the processing of aquatic resources, irrespective of the ecological setting. Contrary to expectations, this association remained stable even after the onset of Holocene warming, including in more southerly areas, where expanding forests provided new opportunities for hunting and gathering. Nevertheless, the results indicate that a broader array of aquatic resources was processed in pottery after the start of the Holocene. We suggest this marks a significant change in the role of pottery of hunter-gatherers, corresponding to an increased volume of production, greater variation in forms and sizes, the rise of intensified fishing, the onset of shellfish exploitation, and reduced residential mobility.}, } @article {pmid30012597, year = {2018}, author = {Kim, S and Maynard, JC and Strickland, A and Burlingame, AL and Milbrandt, J}, title = {Schwann cell O-GlcNAcylation promotes peripheral nerve remyelination via attenuation of the AP-1 transcription factor JUN.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {8019-8024}, pmid = {30012597}, issn = {1091-6490}, support = {R21 NS087306/NS/NINDS NIH HHS/United States ; P41 GM103481/GM/NIGMS NIH HHS/United States ; R56 NS099314/NS/NINDS NIH HHS/United States ; T32 GM108539/GM/NIGMS NIH HHS/United States ; R01 NS105645/NS/NINDS NIH HHS/United States ; RF1 AG013730/AG/NIA NIH HHS/United States ; P50 AG005681/AG/NIA NIH HHS/United States ; R01 AG013730/AG/NIA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Acylation/genetics ; Aging/genetics/metabolism/pathology ; Animals ; Axons/metabolism ; Demyelinating Diseases/genetics/*metabolism/pathology ; Diabetic Neuropathies/genetics/metabolism/pathology ; Gene Deletion ; Mice ; Mice, Knockout ; N-Acetylglucosaminyltransferases/genetics/metabolism ; *Nerve Regeneration ; Oncogene Protein p65(gag-jun)/genetics/*metabolism ; Schwann Cells/*metabolism/pathology ; Sciatic Nerve/*injuries/*metabolism/pathology ; Transcription Factor AP-1/genetics/*metabolism ; }, abstract = {Schwann cells (SCs), the glia of the peripheral nervous system, play an essential role in nerve regeneration. Upon nerve injury, SCs are reprogrammed into unique "repair SCs," and these cells remove degenerating axons/myelin debris, promote axonal regrowth, and ultimately remyelinate regenerating axons. The AP-1 transcription factor JUN is promptly induced in SCs upon nerve injury and potently mediates this injury-induced SC plasticity; however, the regulation of these JUN-dependent SC injury responses is unclear. Previously, we produced mice with a SC-specific deletion of O-GlcNAc transferase (OGT). This enzyme catalyzes O-GlcNAcylation, a posttranslational modification that is influenced by the cellular metabolic state. Mice lacking OGT in SCs develop a progressive demyelinating peripheral neuropathy. Here, we investigated the nerve repair process in OGT-SCKO mutant mice and found that the remyelination of regenerating axons is severely impaired. Gene expression profiling of OGT-SCKO SCs revealed that the JUN-dependent SC injury program was elevated in the absence of injury and failed to shut down at the appropriate time after injury. This aberrant JUN activity results in abnormalities in repair SC function and redifferentiation and prevents the timely remyelination. This aberrant nerve injury response is normalized in OGT-SCKO mice with reduced Jun gene dosage in SCs. Mechanistically, OGT O-GlcNAcylates JUN at multiple sites, which then leads to an attenuation of AP-1 transcriptional activity. Together, these results highlight the metabolic oversight of the nerve injury response via the regulation of JUN activity by O-GlcNAcylation, a pathway that could be important in the neuropathy associated with diabetes and aging.}, } @article {pmid30012596, year = {2018}, author = {Tafoya, S and Liu, S and Castillo, JP and Atz, R and Morais, MC and Grimes, S and Jardine, PJ and Bustamante, C}, title = {Molecular switch-like regulation enables global subunit coordination in a viral ring ATPase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7961-7966}, pmid = {30012596}, issn = {1091-6490}, support = {R00 GM107365/GM/NIGMS NIH HHS/United States ; R01 GM032543/GM/NIGMS NIH HHS/United States ; R01 GM071552/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adenosine Diphosphate/chemistry/metabolism ; *Adenosine Triphosphatases/chemistry/metabolism ; Adenosine Triphosphate/chemistry/metabolism ; Bacillus Phages/*enzymology ; *Models, Biological ; *Viral Proteins/chemistry/metabolism ; }, abstract = {Subunits in multimeric ring-shaped motors must coordinate their activities to ensure correct and efficient performance of their mechanical tasks. Here, we study WT and arginine finger mutants of the pentameric bacteriophage φ29 DNA packaging motor. Our results reveal the molecular interactions necessary for the coordination of ADP-ATP exchange and ATP hydrolysis of the motor's biphasic mechanochemical cycle. We show that two distinct regulatory mechanisms determine this coordination. In the first mechanism, the DNA up-regulates a single subunit's catalytic activity, transforming it into a global regulator that initiates the nucleotide exchange phase and the hydrolysis phase. In the second, an arginine finger in each subunit promotes ADP-ATP exchange and ATP hydrolysis of its neighbor. Accordingly, we suggest that the subunits perform the roles described for GDP exchange factors and GTPase-activating proteins observed in small GTPases. We propose that these mechanisms are fundamental to intersubunit coordination and are likely present in other ring ATPases.}, } @article {pmid30012595, year = {2018}, author = {Przanowski, P and Wasko, U and Zheng, Z and Yu, J and Sherman, R and Zhu, LJ and McConnell, MJ and Tushir-Singh, J and Green, MR and Bhatnagar, S}, title = {Pharmacological reactivation of inactive X-linked Mecp2 in cerebral cortical neurons of living mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7991-7996}, pmid = {30012595}, issn = {1091-6490}, support = {T32 GM008136/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Line ; Cerebral Cortex/*metabolism/pathology ; Humans ; *Methyl-CpG-Binding Protein 2/biosynthesis/genetics/metabolism ; Mice ; Mice, Knockout ; *Mutation ; Neurons/*metabolism/pathology ; Rett Syndrome/drug therapy/genetics/*metabolism/pathology ; }, abstract = {Rett syndrome (RTT) is a genetic disorder resulting from a loss-of-function mutation in one copy of the X-linked gene methyl-CpG-binding protein 2 (MECP2). Typical RTT patients are females and, due to random X chromosome inactivation (XCI), ∼50% of cells express mutant MECP2 and the other ∼50% express wild-type MECP2. Cells expressing mutant MECP2 retain a wild-type copy of MECP2 on the inactive X chromosome (Xi), the reactivation of which represents a potential therapeutic approach for RTT. Previous studies have demonstrated reactivation of Xi-linked MECP2 in cultured cells by biological or pharmacological inhibition of factors that promote XCI (called "XCI factors" or "XCIFs"). Whether XCIF inhibitors in living animals can reactivate Xi-linked MECP2 in cerebral cortical neurons, the cell type most therapeutically relevant to RTT, remains to be determined. Here, we show that pharmacological inhibitors targeting XCIFs in the PI3K/AKT and bone morphogenetic protein signaling pathways reactivate Xi-linked MECP2 in cultured mouse fibroblasts and human induced pluripotent stem cell-derived postmitotic RTT neurons. Notably, reactivation of Xi-linked MECP2 corrects characteristic defects of human RTT neurons including reduced soma size and branch points. Most importantly, we show that intracerebroventricular injection of the XCIF inhibitors reactivates Xi-linked Mecp2 in cerebral cortical neurons of adult living mice. In support of these pharmacological results, we also demonstrate genetic reactivation of Xi-linked Mecp2 in cerebral cortical neurons of living mice bearing a homozygous XCIF deletion. Collectively, our results further establish the feasibility of pharmacological reactivation of Xi-linked MECP2 as a therapeutic approach for RTT.}, } @article {pmid30012594, year = {2018}, author = {Patrinostro, X and Roy, P and Lindsay, A and Chamberlain, CM and Sundby, LJ and Starker, CG and Voytas, DF and Ervasti, JM and Perrin, BJ}, title = {Essential nucleotide- and protein-dependent functions of Actb/β-actin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7973-7978}, pmid = {30012594}, issn = {1091-6490}, support = {R01 AR049899/AR/NIAMS NIH HHS/United States ; R01 DC015495/DC/NIDCD NIH HHS/United States ; }, mesh = {Actins/genetics/*metabolism ; Animals ; Cell Line ; Cytoplasm/genetics/*metabolism ; Embryo, Mammalian/cytology/*metabolism ; Fibroblasts/cytology/*metabolism ; Mice ; Mice, Knockout ; *Models, Biological ; }, abstract = {The highly similar cytoplasmic β- and γ-actins differ by only four functionally similar amino acids, yet previous in vitro and in vivo data suggest that they support unique functions due to striking phenotypic differences between Actb and Actg1 null mouse and cell models. To determine whether the four amino acid variances were responsible for the functional differences between cytoplasmic actins, we gene edited the endogenous mouse Actb locus to translate γ-actin protein. The resulting mice and primary embryonic fibroblasts completely lacked β-actin protein, but were viable and did not present with the most overt and severe cell and organismal phenotypes observed with gene knockout. Nonetheless, the edited mice exhibited progressive high-frequency hearing loss and degeneration of actin-based stereocilia as previously reported for hair cell-specific Actb knockout mice. Thus, β-actin protein is not required for general cellular functions, but is necessary to maintain auditory stereocilia.}, } @article {pmid30012593, year = {2018}, author = {Travis, WR}, title = {Robert W. Kates (1929-2018): Grappled with problems of the human environment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7844-7845}, pmid = {30012593}, issn = {1091-6490}, mesh = {*Environment ; History, 20th Century ; History, 21st Century ; Humans ; Portraits as Topic ; Sociology/*history ; }, } @article {pmid30012592, year = {2018}, author = {Ren, C and Zhang, G and Han, F and Fu, S and Cao, Y and Zhang, F and Zhang, Q and Meslamani, J and Xu, Y and Ji, D and Cao, L and Zhou, Q and Cheung, KL and Sharma, R and Babault, N and Yi, Z and Zhang, W and Walsh, MJ and Zeng, L and Zhou, MM}, title = {Spatially constrained tandem bromodomain inhibition bolsters sustained repression of BRD4 transcriptional activity for TNBC cell growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7949-7954}, pmid = {30012592}, issn = {1091-6490}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Female ; Humans ; Mediator Complex Subunit 1/genetics/metabolism ; Neoplasm Proteins/*antagonists & inhibitors/genetics/metabolism ; Nuclear Proteins/*antagonists & inhibitors/genetics/metabolism ; Transcription Factors/*antagonists & inhibitors/genetics/metabolism ; Transcription, Genetic/*drug effects ; Triple Negative Breast Neoplasms/*drug therapy/metabolism/pathology ; YY1 Transcription Factor/genetics/metabolism ; }, abstract = {The importance of BET protein BRD4 in gene transcription is well recognized through the study of chemical modulation of its characteristic tandem bromodomain (BrD) binding to lysine-acetylated histones and transcription factors. However, while monovalent inhibition of BRD4 by BET BrD inhibitors such as JQ1 blocks growth of hematopoietic cancers, it is much less effective generally in solid tumors. Here, we report a thienodiazepine-based bivalent BrD inhibitor, MS645, that affords spatially constrained tandem BrD inhibition and consequently sustained repression of BRD4 transcriptional activity in blocking proliferation of solid-tumor cells including a panel of triple-negative breast cancer (TNBC) cells. MS645 blocks BRD4 binding to transcription enhancer/mediator proteins MED1 and YY1 with potency superior to monovalent BET inhibitors, resulting in down-regulation of proinflammatory cytokines and genes for cell-cycle control and DNA damage repair that are largely unaffected by monovalent BrD inhibition. Our study suggests a therapeutic strategy to maximally control BRD4 activity for rapid growth of solid-tumor TNBC cells.}, } @article {pmid30012591, year = {2018}, author = {Wie, DS and Zhang, Y and Kim, MK and Kim, B and Park, S and Kim, YJ and Irazoqui, PP and Zheng, X and Xu, B and Lee, CH}, title = {Wafer-recyclable, environment-friendly transfer printing for large-scale thin-film nanoelectronics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7236-E7244}, pmid = {30012591}, issn = {1091-6490}, abstract = {Transfer printing of thin-film nanoelectronics from their fabrication wafer commonly requires chemical etching on the sacrifice of wafer but is also limited by defects with a low yield. Here, we introduce a wafer-recyclable, environment-friendly transfer printing process that enables the wafer-scale separation of high-performance thin-film nanoelectronics from their fabrication wafer in a defect-free manner that enables multiple reuses of the wafer. The interfacial delamination is enabled through a controllable cracking phenomenon in a water environment at room temperature. The physically liberated thin-film nanoelectronics can be then pasted onto arbitrary places of interest, thereby endowing the particular surface with desirable add-on electronic features. Systematic experimental, theoretical, and computational studies reveal the underlying mechanics mechanism and guide manufacturability for the transfer printing process in terms of scalability, controllability, and reproducibility.}, } @article {pmid30012590, year = {2018}, author = {Luis, AD and Kuenzi, AJ and Mills, JN}, title = {Species diversity concurrently dilutes and amplifies transmission in a zoonotic host-pathogen system through competing mechanisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7979-7984}, pmid = {30012590}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; *Hantavirus Pulmonary Syndrome/epidemiology/transmission ; *Host-Parasite Interactions ; Humans ; *Models, Biological ; Prevalence ; Sin Nombre virus/*physiology ; United States/epidemiology ; *Zoonoses/epidemiology/transmission ; }, abstract = {In this era of unprecedented biodiversity loss and increased zoonotic disease emergence, it is imperative to understand the effects of biodiversity on zoonotic pathogen dynamics in wildlife. Whether increasing biodiversity should lead to a decrease or increase in infection prevalence, termed the dilution and amplification effects, respectively, has been hotly debated in disease ecology. Sin Nombre hantavirus, which has an ∼35% mortality rate when it spills over into humans, occurs at a lower prevalence in the reservoir host, the North American deermouse, in areas with higher small mammal diversity-a dilution effect. However, the mechanism driving this relationship is not understood. Using a mechanistic mathematical model of infection dynamics and a unique long-term, high-resolution, multisite dataset, it appears that the observed dilution effect is a result of increasing small-mammal diversity leading to decreased deermouse population density and, subsequently, prevalence (a result of density-dependent transmission). However, once density is taken into account, there is an increase in the transmission rate at sites with higher diversity-a component amplification effect. Therefore, dilution and amplification are occurring at the same time in the same host-pathogen system; there is a component amplification effect (increase in transmission rate), but overall a net dilution because the effect of diversity on reservoir host population density is stronger. These results suggest we should focus on how biodiversity affects individual mechanisms that drive prevalence and their relative strengths if we want to make generalizable predictions across host-pathogen systems.}, } @article {pmid30012589, year = {2018}, author = {Baliga, RS and Preedy, MEJ and Dukinfield, MS and Chu, SM and Aubdool, AA and Bubb, KJ and Moyes, AJ and Tones, MA and Hobbs, AJ}, title = {Phosphodiesterase 2 inhibition preferentially promotes NO/guanylyl cyclase/cGMP signaling to reverse the development of heart failure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7428-E7437}, pmid = {30012589}, issn = {1091-6490}, support = {PG/10/077/28554//British Heart Foundation/United Kingdom ; }, mesh = {Animals ; Cells, Cultured ; Cyclic GMP/analysis/*physiology ; Cyclic Nucleotide Phosphodiesterases, Type 2/*physiology ; Guanylate Cyclase/*physiology ; Heart Failure/*drug therapy ; Male ; Mice ; Nitric Oxide/*physiology ; Phosphodiesterase Inhibitors/*pharmacology ; Signal Transduction/*physiology ; }, abstract = {Heart failure (HF) is a shared manifestation of several cardiovascular pathologies, including hypertension and myocardial infarction, and a limited repertoire of treatment modalities entails that the associated morbidity and mortality remain high. Impaired nitric oxide (NO)/guanylyl cyclase (GC)/cyclic guanosine-3',5'-monophosphate (cGMP) signaling, underpinned, in part, by up-regulation of cyclic nucleotide-hydrolyzing phosphodiesterase (PDE) isozymes, contributes to the pathogenesis of HF, and interventions targeted to enhancing cGMP have proven effective in preclinical models and patients. Numerous PDE isozymes coordinate the regulation of cardiac cGMP in the context of HF; PDE2 expression and activity are up-regulated in experimental and human HF, but a well-defined role for this isoform in pathogenesis has yet to be established, certainly in terms of cGMP signaling. Herein, using a selective pharmacological inhibitor of PDE2, BAY 60-7550, and transgenic mice lacking either NO-sensitive GC-1α (GC-1α-/-) or natriuretic peptide-responsive GC-A (GC-A-/-), we demonstrate that the blockade of PDE2 promotes cGMP signaling to offset the pathogenesis of experimental HF (induced by pressure overload or sympathetic hyperactivation), reversing the development of left ventricular hypertrophy, compromised contractility, and cardiac fibrosis. Moreover, we show that this beneficial pharmacodynamic profile is maintained in GC-A-/- mice but is absent in animals null for GC-1α or treated with a NO synthase inhibitor, revealing that PDE2 inhibition preferentially enhances NO/GC/cGMP signaling in the setting of HF to exert wide-ranging protection to preserve cardiac structure and function. These data substantiate the targeting of PDE2 in HF as a tangible approach to maximize myocardial cGMP signaling and enhancing therapy.}, } @article {pmid30012588, year = {2018}, author = {}, title = {Correction for Fregel et al., Ancient genomes from North Africa evidence prehistoric migrations to the Maghreb from both the Levant and Europe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7231}, doi = {10.1073/pnas.1811169115}, pmid = {30012588}, issn = {1091-6490}, } @article {pmid30012423, year = {2018}, author = {Hoog, TG and Fredrickson, SJ and Hsu, CW and Senger, SM and Dickinson, ME and Udan, RS}, title = {The effects of reduced hemodynamic loading on morphogenesis of the mouse embryonic heart.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {127-137}, doi = {10.1016/j.ydbio.2018.07.007}, pmid = {30012423}, issn = {1095-564X}, mesh = {Animals ; Biomechanical Phenomena/physiology ; Heart/*embryology ; Hemodynamics/*physiology ; Mice/embryology ; Morphogenesis/physiology ; Myocardium/pathology ; Organogenesis ; Stress, Mechanical ; }, abstract = {Development of the embryonic heart involves an intricate network of biochemical and genetic cues to ensure its proper growth and morphogenesis. However, studies from avian and teleost models reveal that biomechanical force, namely hemodynamic loading (blood pressure and shear stress), plays a significant role in regulating heart development. To study how hemodynamic loading impacts development of the mammalian embryonic heart, we utilized mouse embryo culture and manipulation techniques and performed optical projection tomography imaging followed by morphometric analysis to determine how reduced-loading affects heart volume, myocardial thickness, trabeculation and looping. Our results reveal that hemodynamic loading can regulate these features at different thresholds. Intermediate levels of hemodynamic loading are sufficient to promote proper myocardial growth and heart size, but insufficient to promote looping and trabeculation. Whereas, low levels of hemodynamic loading fails to promote proper growth of the myocardium and heart size. These results reveal that the regulation of heart development by biomechanical force is conserved across many vertebrate classes, and this study begins to elucidate how these specific forces regulate development of the mammalian heart.}, } @article {pmid30012221, year = {2018}, author = {Furmanik, M and Shanahan, CM}, title = {ER stress regulates alkaline phosphatase gene expression in vascular smooth muscle cells via an ATF4-dependent mechanism.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {483}, pmid = {30012221}, issn = {1756-0500}, support = {FS/11/9/28695//British Heart Foundation/United Kingdom ; }, mesh = {Activating Transcription Factor 4/metabolism ; Alkaline Phosphatase/*metabolism ; Cells, Cultured ; *Endoplasmic Reticulum Stress ; Humans ; Muscle, Smooth, Vascular/*enzymology ; Myocytes, Smooth Muscle ; Osteogenesis ; }, abstract = {OBJECTIVE: Vascular calcification is the deposition of hydroxyapatite crystals in the blood vessel wall. Osteogenic differentiation of vascular smooth muscle cells (VSMCs) plays a key role in this process. Increased expression of alkaline phosphatase (ALP) occurs in some in vitro models of VSMC calcification and is thought to be crucial for mineralization, however, little is known about the transcriptional regulation of ALP in VSMCs. Recently, ALP upregulation was shown to coincide with endoplasmic reticulum (ER) stress-mediated vascular calcification, specifically with expression of the transcription factor ATF4. As no direct links between ALP expression and ER stress have previously been demonstrated in VSMCs, the aim of this study was to investigate whether ATF4 interacts directly with the ALP promoter.

RESULTS: The present study shows that ALP mRNA and activity were significantly increased by ER stress treatment of human primary VSMCs in vitro and that this was ATF4-dependent. Bioinformatics analysis predicted two ATF4 binding sites in ER-stress responsive regions of the ALP promoter (- 3631 to - 2048 bp from the first intron). However, we found that ATF4 does not bind within this fragment of the ALP promoter region.}, } @article {pmid30012215, year = {2018}, author = {Arachchi, PS and Weerasekera, MM and Seneviratne, B and Weerasekera, D and Fernando, N and Gunasekara, CP}, title = {Imprint cytology: a useful screening test for diagnosis of Helicobacter pylori in resource poor settings.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {481}, pmid = {30012215}, issn = {1756-0500}, support = {NSF/SCH/2015/04//National Science Foundation/ ; ASP/01/RE/MED/2017/28//University of Sri Jayewardenepura/ ; }, mesh = {Adult ; Azure Stains ; Biopsy ; Helicobacter Infections/*diagnosis ; Helicobacter pylori/*isolation & purification ; Humans ; Sensitivity and Specificity ; Sri Lanka ; *Staining and Labeling ; }, abstract = {OBJECTIVE: The study aimed to compare the usefulness of two staining methods for imprint cytology for diagnosis of Helicobacter pylori infection. Gastric biopsy specimens (from dyspeptic patients attending routine upper gastrointestinal endoscopy) were placed on glass slides to obtain imprints. The imprints were stained with Toluidine blue and Giemsa stains separately and observed under ×400 magnification using a light microscope. Imprinted biopsies were sectioned and stained with H & E stain and Giemsa stain for histological analysis. Diagnosis of H. pylori infection in both imprint and histological sections were confirmed by a consultant pathologist. The sensitivity, specificity, positive predictive value and negative predictive value of each stain were calculated and benchmarked against histological diagnosis.

RESULTS: Of the 55 dyspeptic patients enrolled in the study, 5 were positive for H. pylori by Toluidine blue stain and 4 by Giemsa stain. The sensitivity of Toluidine blue stain (57.1%) was higher than Giemsa stain (42.9%) while the specificity of both stains was equal (97.9%). Giemsa stain gave a better discrimination for identification of H. pylori bacteria among the mucosal background. Imprint cytology is a rapid, simple and cost effective diagnosis method that can supplement histological diagnosis.}, } @article {pmid30012214, year = {2018}, author = {Chilinda, GK and Gadama, LA and Stones, W}, title = {Point-of-care umbilical arterial lactate and newborn outcomes in a low resource setting: cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {477}, pmid = {30012214}, issn = {1756-0500}, mesh = {Adult ; Apgar Score ; *Asphyxia Neonatorum ; Cohort Studies ; Female ; Humans ; Infant, Newborn ; Lactic Acid/*blood ; Malawi ; *Point-of-Care Systems ; Pregnancy ; Umbilical Arteries/*chemistry ; }, abstract = {OBJECTIVE: Birth asphyxia contributes substantially to the burden of intrapartum stillbirth and neonatal mortality in resource limited countries. We investigated clinical correlates and neonatal outcomes of lactate analysis of umbilical arterial cord blood in a large referral maternity unit in Malawi using a point-of-care test (Lactate Xpress, Nova Biomedical, Runcorn, UK) and examined maternal and neonatal characteristics and outcomes.

RESULTS: There were 389 live births and 12 intrapartum stillbirths during the study. The median umbilical arterial lactate concentration was 3.4 mmol/L (interquartile range 2.6-4.9). Umbilical arterial lactate concentrations among the 45 babies admitted for special neonatal care were above 5 mmol/L in 16/45 (36%) of cases, with no fatality below 13 mmol/L. A positive malaria rapid diagnostic test was associated with hyperlactatemia (p < 0.05). In receiver-operator characteristic (ROC) analysis using a lactate cutoff of 5 mmol/L, areas under the curve were 0.72 (95% CI 0.66-0.79) and 0.64 (95% CI 0.58-0.69) for the Apgar score at 1 and 5 min respectively. This approach can identify safely those newborns that are unlikely to require additional monitoring. Scale-up implementation research in low resource country referral units is needed. The influence of malaria on neonatal hyperlactatemia requires further exploration.}, } @article {pmid30012207, year = {2018}, author = {Sharyan, A and Gonzalez, C and Ukaegbu, O and Powell, K and McCarthy, PC}, title = {Determination of the binding affinities of Neisseria meningitidis serogroup W capsule polymerase with two nucleotide sugar substrates.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {482}, pmid = {30012207}, issn = {1756-0500}, support = {UL1 GM118973/GM/NIGMS NIH HHS/United States ; UL1GM118973//National Institute of General Medical Sciences/ ; }, mesh = {DNA-Directed DNA Polymerase/*metabolism ; Neisseria meningitidis/enzymology/*immunology ; Nucleotides/chemistry ; Polysaccharides/chemistry ; Serogroup ; Sugars ; }, abstract = {OBJECTIVE: Meningococcal meningitis is a public health burden. Immunization strategies have reduced global incidence of the disease. Glycoconjugate vaccines are the most effective type of vaccine to combat most causes of meningococcal meningitis. These vaccines contain capsular polysaccharide fragments from disease-causing serogroups of Neisseria meningitidis that are chemically attached to a carrier protein. The enzymes responsible for capsular polysaccharide synthesis can serve as tools to make these critical vaccine components. One such enzyme is the N. meningitidis serogroup W capsule polymerase. This enzyme is responsible for creating the galactose-sialic acid containing capsular polysaccharide of this serogroup. Our aim in this study was to determine the binding affinities of nucleotide sugar donors CMP-sialic acid and UDP-galactose using a coupled transferase assay to inform future work to modulate polysaccharide synthesis by this enzyme.

RESULTS: We determined a Km of 66.8 µM for CMP-sialic acid and a Km for UDP-galactose of 3.9 µM. These values are lower than reported values for other retaining galactosyltransferases and inverting sialyltransferases respectively. There were difficulties obtaining reliable data for galactosyltransferase activity. An alternate strategy is needed to assess kinetic parameters of the separate transferase activities for this enzyme.}, } @article {pmid30012204, year = {2018}, author = {Murphy, A and Kirby, A and Bradley, C}, title = {Knowledge is power: general practitioners prescribing of new oral anticoagulants in Ireland.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {478}, pmid = {30012204}, issn = {1756-0500}, mesh = {Adult ; Anticoagulants/*therapeutic use ; Female ; *General Practitioners ; Guideline Adherence ; Humans ; Ireland ; Male ; Middle Aged ; *Practice Patterns, Physicians' ; Warfarin/*therapeutic use ; }, abstract = {OBJECTIVE: New oral anticoagulants (NOACs) aim to overcome warfarin's shortcomings, however their pharmacokinetic characteristics make prescribing complex. Thus it is imperative that general practitioners (GPs) are aware of specific treatments so as to maximise their benefits and minimise their pitfalls. This study explores GPs attitudes and experiences with prescribing NOACs in Ireland where, despite clear national prescribing guidelines advocating warfarin as first line therapy, the number of patients being prescribed NOACs for the first time is growing.

RESULTS: Using primary data collected from GPs in Ireland the factors influencing the likelihood of a GP initiating a prescription for a NOAC are determined using a probit model. Results indicate 46% of the sample initiated NOAC prescriptions and GP practice size is a significant factor influencing this. Analysis revealed no difference regarding the sources of information considered important amongst GPs when prescribing new drugs. However, there were differences in which factors were considered important when prescribing anticoagulants between initiating and non-initiating NOAC prescribers. The results of this study suggest better utilisation of existing information and education tools for GPs prescribing NOACs and managing NOAC patients is imperative, to ensure the right anticoagulant is prescribed for the right patient at the right time.}, } @article {pmid30012199, year = {2018}, author = {Abdullah, NL and Gunasekaran, R and Mohd-Zin, SW and Lim, BH and Maniam, P and Mohd-Salleh, AS and Thong, MK and Chik, Z and Nordin, N and Omar, Z and Engkasan, JP and Ganesan, D and Aiezzah, ZN and Ahmad-Annuar, A and Abdul-Aziz, NM}, title = {Cranial neural tube defect after trimethoprim exposure.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {475}, pmid = {30012199}, issn = {1756-0500}, support = {UM.C/625/1/HIR/062//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/062//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/062//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/062//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/148/2//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/148/2//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/148/2//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/148/2//University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/MOHE/MED/08//Ministry of Higher Education University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/MOHE/MED/08//Ministry of Higher Education University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/MOHE/MED/08//Ministry of Higher Education University of Malaya High Impact Research Grant/ ; UM.C/625/1/HIR/MOHE/MED/08//Ministry of Higher Education University of Malaya High Impact Research Grant/ ; PG153-2015B//University of Malaya Postgraduate Research Grant (PPP)/ ; PG153-2015B//University of Malaya Postgraduate Research Grant (PPP)/ ; PG137-2015A//University of Malaya Postgraduate Research Grant (PPP)/ ; PG137-2015A//University of Malaya Postgraduate Research Grant (PPP)/ ; }, mesh = {Animals ; Anti-Infective Agents, Urinary/*toxicity ; Female ; Germany ; Japan ; Malaysia ; Male ; Mice ; Neural Tube Defects/*chemically induced ; Pregnancy ; Taiwan ; Trimethoprim/*toxicity ; }, abstract = {OBJECTIVES: The Neural Tube Defects Research Group of University of Malaya was approached to analyze a tablet named TELSE, which may have resulted in a baby born with central nervous system malformation at the University of Malaya Medical Centre. In this animal experimental study, we investigated the content of TELSE and exposure of its contents that resulted in failure of primary neurulation.

RESULTS: Liquid Chromatography Tandem Mass spectrophotometry analysis of the TELSE tablet confirmed the presence of trimethoprim as the active compound. The TELSE tablet-treated females produced significant numbers of embryos with exencephaly (n = 8, 36.4%, *P < 0.0001), in all litters. The TELSE tablet-treated females subsequently given folic acid did not result in pregnancies despite there being evidence of possible resorption. Furthermore, after multiple rounds of mating which did not yield viable pregnancies, eventually, 2 embryos with exencephaly were harvested in a litter of 6 at 0.05% w/v pure trimethoprim once. The use of trimethoprim, a folic acid antagonist, peri-conceptionally increased the risk of exencephaly in the mouse.}, } @article {pmid30012198, year = {2018}, author = {Nkembe, NM and Kamga, HG and Baiye, WA and Chafa, AB and Njotang, PN}, title = {Streptococcus agalactiae prevalence and antimicrobial susceptibility pattern in vaginal and anorectal swabs of pregnant women at a tertiary hospital in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {480}, pmid = {30012198}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents ; Anti-Infective Agents ; Cameroon/epidemiology ; Cross-Sectional Studies ; Female ; Humans ; Infant, Newborn ; Microbial Sensitivity Tests ; Middle Aged ; Pregnancy ; Pregnancy Complications, Infectious ; Prevalence ; Streptococcal Infections/drug therapy/*epidemiology ; Streptococcus agalactiae/drug effects/*isolation & purification ; Tertiary Care Centers ; Vagina/*microbiology ; Young Adult ; }, abstract = {OBJECTIVE: Group B Streptococcus (GBS) or Streptococcus agalactiae is part of the normal flora of the gut and genital tract, thus carrier pregnant women can transmit this germ to newborns which could cause early neonatal infection. In Cameroon, few studies have been conducted on GBS, thus this study sought to detect the rectal and vaginal colonization rates and the antibiotic susceptibility profile of the identified strains in pregnant women. We therefore conducted a cross-sectional study over a 6 months period analysing vaginal and anorectal samples obtained from 100 pregnant women. Cultures for the isolation of GBS were carried out according to standard microbiological methods and grouping done using the Pastorex strep Kit. All strains isolated were used for susceptibility test to various antibiotics as recommended by the French microbiology society, using the disk-diffusion method.

RESULTS: The detected colonization rate was 14%. No resistance to ampicillin, oxacillin, amoxycillin-clavulanate, cefotaxime, pristinamycin, vancomycin and clindamycin was found. Just 12, 94 and 82% of strains showed sensitivity to gentamycin, erythromycin and cefoxitin respectively. This study therefore revealed that at least one out of every ten women is GBS colonized and strains showed uniform sensitivity to beta lactamines. However, decreased sensitivity to erythromycin was detected.}, } @article {pmid30012196, year = {2018}, author = {Gerensea, H and Kebede, A and Baraki, Z and Berihu, H and Zeru, T and Birhane, E and G/Her, D and Hintsa, S and Siyum, H and Kahsay, G and Gidey, G and Teklay, G and Mulatu, G}, title = {Consistency of Integrated Management of Newborn and Childhood Illness (IMNCI) in Shire Governmental Health Institution in 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {476}, pmid = {30012196}, issn = {1756-0500}, mesh = {Child ; *Child Health Services ; Child, Preschool ; *Disease Management ; Government ; *Health Facilities ; Humans ; Infant ; *Infant Mortality ; }, abstract = {OBJECTIVE: In an effort to reduce infant mortality and morbidity, the World Health Organization and other technical partners developed the Integrated Management of Newborn and Childhood Illness (IMNCI). This study focuses on assessment of consistency and completeness of integrated management of neonatal and child hood illness in primary health care units.

RESULTS: A total of 384 cases were taken from 3562 cases both from young infant registration (under-2 month old) and child registration (2 months-5 year old). Out of 384 cases, 241 (62.8%) cases were correctly classified and 143 (37.2%) were incorrect classifications. Similarly 164 (42.7%) cases were treated correctly where as 220 (57.3%) treated incorrectly. Only 95 (24.7%) cases have given appropriate appointments where as 289 (75.3%) cases were appointed incorrectly. The overall consistency of IMNCI management is poor. Unless continuous follow up of and training was given, children are not treated as expected. More over using electronic method of IMNCI may alleviate the problem.}, } @article {pmid30012191, year = {2018}, author = {Sakurai, D and Uchida, R and Ihara, F and Kunii, N and Nakagawa, T and Chazono, H and Hanazawa, T and Motohashi, S and Okamoto, Y}, title = {Immunosuppressive property of submandibular lymph nodes in patients with head and neck tumors: differential distribution of regulatory T cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {479}, pmid = {30012191}, issn = {1756-0500}, support = {15K107999//Japan Society for the Promotion of Science/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Forkhead Transcription Factors ; Head and Neck Neoplasms/*immunology ; Humans ; Killer Cells, Natural ; Lymph Nodes/*immunology ; Middle Aged ; Neck ; *T-Lymphocytes, Regulatory ; }, abstract = {OBJECTIVE: Different sensitizations and immune responses are thought to be induced in response to antigens at different mucosal sites between the oral floor and nose. The aim of this study was to investigate differences in the distributions of lymphocyte subsets in the submandibular (SM) and upper jugular (UJ) lymph nodes (LNs), which are supposed to be regional LNs of the oral floor and nasal mucosa, respectively. SMLNs and UJLNs were collected from patients with head and neck tumors who underwent surgical resection. The populations of T cells, Natural Killer (NK) cells, Natural Killer T (NKT) cells, regulatory T cells (Tregs) and dendritic cells (DCs) in LNs without metastasis were analyzed by flow cytometry. The high-affinity IgE receptor (FcεRI) expression of LN cells were also evaluated.

RESULTS: The proportions of CD4+CD25+Foxp3+ Tregs, CD4+CD45RA-Foxp3high effector Tregs and FcεRIα+CD33+CD11c+ DCs were significantly larger in SMLNs compared with UJLNs, while those of CD3+ T cells, CD3-CD56+ NK cells, CD3+Vα24+Vβ11+ NKT cells, and CD123+CD303+ DCs did not show any significant differences between SMLNs and UJLNs. The differential distributions of CD4+CD25+Foxp3+ Tregs were observed regardless of tumor region, LN metastasis and clinical staging. These data indicate that SMLNs may have immunosuppressive properties compared with UJLNs.}, } @article {pmid30012138, year = {2018}, author = {Krishnan, P and Meile, L and Plissonneau, C and Ma, X and Hartmann, FE and Croll, D and McDonald, BA and Sánchez-Vallet, A}, title = {Transposable element insertions shape gene regulation and melanin production in a fungal pathogen of wheat.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {78}, pmid = {30012138}, issn = {1741-7007}, abstract = {BACKGROUND: Fungal plant pathogens pose major threats to crop yield and sustainable food production if they are highly adapted to their host and the local environment. Variation in gene expression contributes to phenotypic diversity within fungal species and affects adaptation. However, very few cases of adaptive regulatory changes have been reported in fungi and the underlying mechanisms remain largely unexplored. Fungal pathogen genomes are highly plastic and harbor numerous insertions of transposable elements, which can potentially contribute to gene expression regulation. In this work, we elucidated how transposable elements contribute to variation in melanin accumulation, a quantitative trait in fungi that affects survival under stressful conditions.

RESULTS: We demonstrated that differential transcriptional regulation of the gene encoding the transcription factor Zmr1, which controls expression of the genes in the melanin biosynthetic gene cluster, is responsible for variation in melanin accumulation in the fungal plant pathogen Zymoseptoria tritici. We show that differences in melanin levels between two strains of Z. tritici are due to two levels of transcriptional regulation: (1) variation in the promoter sequence of Zmr1 and (2) an insertion of transposable elements upstream of the Zmr1 promoter. Remarkably, independent insertions of transposable elements upstream of Zmr1 occurred in 9% of Z. tritici strains from around the world and negatively regulated Zmr1 expression, contributing to variation in melanin accumulation.

CONCLUSIONS: Our studies identified two levels of transcriptional control that regulate the synthesis of melanin. We propose that these regulatory mechanisms evolved to balance the fitness costs associated with melanin production against its positive contribution to survival in stressful environments.}, } @article {pmid30012125, year = {2018}, author = {Maharana, SK and Schlosser, G}, title = {A gene regulatory network underlying the formation of pre-placodal ectoderm in Xenopus laevis.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {79}, pmid = {30012125}, issn = {1741-7007}, abstract = {BACKGROUND: The neural plate border ectoderm gives rise to key developmental structures during embryogenesis, including the neural crest and the preplacodal ectoderm. Many sensory organs and ganglia of vertebrates develop from cranial placodes, which themselves arise from preplacodal ectoderm, defined by expression of transcription factor Six1 and its coactivator Eya1. Here we elucidate the gene regulatory network underlying the specification of the preplacodal ectoderm in Xenopus, and the functional interactions among transcription factors that give rise to this structure.

RESULTS: To elucidate the gene regulatory network upstream of preplacodal ectoderm formation, we use gain- and loss-of-function studies to explore the role of early ectodermal transcription factors for establishing the preplacodal ectoderm and adjacent ectodermal territories, and the role of Six1 and Eya1 in feedback regulation of these transcription factors. Our findings suggest that transcription factors with expression restricted to ventral (non-neural) ectoderm (AP2, Msx1, FoxI1, Vent2, Dlx3, GATA2) and those restricted to dorsal (neural) ectoderm (Pax3, Hairy2b, Zic1) are required for specification of both preplacodal ectoderm and neural crest in a context-dependent fashion and are cross-regulated by Eya1 and Six1.

CONCLUSION: These findings allow us to elucidate a detailed gene regulatory network at the neural plate border upstream of preplacodal ectoderm formation based on functional interactions between ectodermal transcription factors. We propose a new model to explain the formation of immediately juxtaposed preplacodal ectoderm and neural crest territories at the neural plate border, uniting previous models.}, } @article {pmid30012108, year = {2018}, author = {Bukhari, SAC and Martínez-Romero, M and O' Connor, MJ and Egyedi, AL and Willrett, D and Graybeal, J and Musen, MA and Cheung, KH and Kleinstein, SH}, title = {CEDAR OnDemand: a browser extension to generate ontology-based scientific metadata.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {268}, pmid = {30012108}, issn = {1471-2105}, support = {U54 AI117925/AI/NIAID NIH HHS/United States ; U54AI117925//NIH BIG DATA TO KNOWLEDGE/ ; }, abstract = {BACKGROUND: Public biomedical data repositories often provide web-based interfaces to collect experimental metadata. However, these interfaces typically reflect the ad hoc metadata specification practices of the associated repositories, leading to a lack of standardization in the collected metadata. This lack of standardization limits the ability of the source datasets to be broadly discovered, reused, and integrated with other datasets. To increase reuse, discoverability, and reproducibility of the described experiments, datasets should be appropriately annotated by using agreed-upon terms, ideally from ontologies or other controlled term sources.

RESULTS: This work presents "CEDAR OnDemand", a browser extension powered by the NCBO (National Center for Biomedical Ontology) BioPortal that enables users to seamlessly enter ontology-based metadata through existing web forms native to individual repositories. CEDAR OnDemand analyzes the web page contents to identify the text input fields and associate them with relevant ontologies which are recommended automatically based upon input fields' labels (using the NCBO ontology recommender) and a pre-defined list of ontologies. These field-specific ontologies are used for controlling metadata entry. CEDAR OnDemand works for any web form designed in the HTML format. We demonstrate how CEDAR OnDemand works through the NCBI (National Center for Biotechnology Information) BioSample web-based metadata entry.

CONCLUSION: CEDAR OnDemand helps lower the barrier of incorporating ontologies into standardized metadata entry for public data repositories. CEDAR OnDemand is available freely on the Google Chrome store https://chrome.google.com/webstore/search/CEDAROnDemand.}, } @article {pmid30012097, year = {2018}, author = {Rodríguez Lorenzo, JL and Hobza, R and Vyskot, B}, title = {DNA methylation and genetic degeneration of the Y chromosome in the dioecious plant Silene latifolia.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {540}, pmid = {30012097}, issn = {1471-2164}, support = {P501/12/G090//Czech Science Foundation/ ; }, mesh = {*Chromosomes, Plant ; *DNA Methylation ; DNA, Plant/chemistry ; *Evolution, Molecular ; Gene Expression ; Plant Leaves/metabolism ; Sequence Homology, Nucleic Acid ; Silene/*genetics/metabolism ; }, abstract = {BACKGROUND: S. latifolia is a model organism for the study of sex chromosome evolution in plants. Its sex chromosomes include large regions in which recombination became gradually suppressed. The regions tend to expand over time resulting in the formation of evolutionary strata. Non-recombination and later accumulation of repetitive sequences is a putative cause of the size increase in the Y chromosome. Gene decay and accumulation of repetitive DNA are identified as key evolutionary events. Transposons in the X and Y chromosomes are distributed differently and there is a regulation of transposon insertion by DNA methylation of the target sequences, this points to an important role of DNA methylation during sex chromosome evolution in Silene latifolia. The aim of this study was to elucidate whether the reduced expression of the Y allele in S. latifolia is caused by genetic degeneration or if the cause is methylation triggered by transposons and repetitive sequences.

RESULTS: Gene expression analysis in S. latifolia males has shown expression bias in both X and Y alleles. To determine whether these differences are caused by genetic degeneration or methylation spread by transposons and repetitive sequences, we selected several sex-linked genes with varying degrees of degeneration and from different evolutionary strata. Immunoprecipitation of methylated DNA (MeDIP) from promoter, exon and intron regions was used and validated through bisulfite sequencing. We found DNA methylation in males, and only in the promoter of genes of stratum I (older). The Y alleles in genes of stratum I were methylation enriched compared to X alleles. There was also abundant and high percentage methylation in the CHH context in most sequences, indicating de novo methylation through the RdDM pathway.

CONCLUSIONS: We speculate that TE accumulation and not gene decay is the cause of DNA methylation in the S. latifolia Y sex chromosome with influence on the process of heterochromatinization.}, } @article {pmid30012096, year = {2018}, author = {Guo, J and Huang, J and Zhou, Y and Zhou, Y and Yu, L and Li, H and Hou, L and Zhu, L and Ge, D and Zeng, Y and Guleng, B and Li, Q}, title = {Germline and somatic variations influence the somatic mutational signatures of esophageal squamous cell carcinomas in a Chinese population.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {538}, pmid = {30012096}, issn = {1471-2164}, support = {31371289//National Natural Science Foundation of China/ ; 3502Z20149030//Major Disease Research Projects of Xiamen/ ; 2018J01054//Natural Science Foundation of Fujian Province/ ; JAT170004//Education and Research Foundation for Young Scholars of Education department of Fujian Province/ ; }, mesh = {Apc3 Subunit, Anaphase-Promoting Complex-Cyclosome/genetics ; Asian Continental Ancestry Group/*genetics ; Carcinoma, Squamous Cell/*genetics/pathology ; China ; DNA Copy Number Variations ; Databases, Genetic ; Esophageal Neoplasms/*genetics/pathology ; Genetic Loci ; Genetic Predisposition to Disease ; Genome, Human ; Genotype ; Germ Cells/metabolism ; Humans ; INDEL Mutation ; Polymorphism, Single Nucleotide ; Risk Factors ; Transcription Factors/genetics ; }, abstract = {BACKGROUND: Esophageal squamous cell carcinomas (ESCC) is the fourth most lethal cancer in China. Previous studies reveal several highly conserved mutational processes in ESCC. However, it remains unclear what are the true regulators of the mutational processes.

RESULTS: We analyzed the somatic mutational signatures in 302 paired whole-exome sequencing data of ESCC in a Chinese population for potential regulators of the mutational processes. We identified three conserved subtypes based on the mutational signatures with significantly different clinical outcomes. Our results show that patients of different subpopulations of Chinese differ significantly in the activity of the "NpCpG" signature (FDR = 0.00188). In addition, we report ZNF750 and CDC27, of which the somatic statuses and the genetic burdens consistently influence the activities of specific mutational signatures in ESCC: the somatic ZNF750 status is associated with the AID/APOBEC-related mutational process (FDR = 0.0637); the somatic CDC27 copy-number is associated with the "NpCpG" (FDR = 0.00615) and the AID/APOBEC-related mutational processes (FDR = 8.69 × 10- 4). The burdens of germline variants in the two genes also significantly influence the activities of the same somatic mutational signatures (FDR < 0.1).

CONCLUSIONS: We report multiple factors that influence the mutational processes in ESCC including: the subpopulations of Chinese; the germline and somatic statuses of ZNF750 and CDC27 and exposure to alcohol and tobacco. Our findings based on the evidences from both germline and somatic levels reveal potential genetic regulators of the somatic mutational processes and provide insights into the biology of esophageal carcinogenesis.}, } @article {pmid30012095, year = {2018}, author = {Seal, A and Wild, DJ}, title = {Netpredictor: R and Shiny package to perform drug-target network analysis and prediction of missing links.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {265}, pmid = {30012095}, issn = {1471-2105}, abstract = {BACKGROUND: Netpredictor is an R package for prediction of missing links in any given unipartite or bipartite network. The package provides utilities to compute missing links in a bipartite and well as unipartite networks using Random Walk with Restart and Network inference algorithm and a combination of both. The package also allows computation of Bipartite network properties, visualization of communities for two different sets of nodes, and calculation of significant interactions between two sets of nodes using permutation based testing. The application can also be used to search for top-K shortest paths between interactome and use enrichment analysis for disease, pathway and ontology. The R standalone package (including detailed introductory vignettes) and associated R Shiny web application is available under the GPL-2 Open Source license and is freely available to download.

RESULTS: We compared different algorithms performance in different small datasets and found random walk supersedes rest of the algorithms. The package is developed to perform network based prediction of unipartite and bipartite networks and use the results to understand the functionality of proteins in an interactome using enrichment analysis.

CONCLUSION: The rapid application development envrionment like shiny, helps non programmers to develop fast rich visualization apps and we beleieve it would continue to grow in future with further enhancements. We plan to update our algorithms in the package in near future and help scientist to analyse data in a much streamlined fashion.}, } @article {pmid30012094, year = {2018}, author = {Chen, Y and Fokar, M and Kang, M and Chen, N and Allen, RD and Chen, Y}, title = {Phosphorylation of Arabidopsis SINA2 by CDKG1 affects its ubiquitin ligase activity.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {147}, pmid = {30012094}, issn = {1471-2229}, support = {201406300140//China Scholarship Council/ ; 2004-35304-15002//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: SEVEN IN ABSENTIA (SINA) is a RING domain-containing ubiquitin ligase involved in Drosophila eye formation. SINA-like proteins in plants are involved in several signaling pathways. Of the 18 SINA-like proteins identified in Arabidopsis, SEVEN IN ABSENTIA 2 (SINA2) lacks a canonical RING domain and is thought to lack ubiquitin ligase activity.

RESULTS: Our results show that SINA2 has E3 ligase activity in vitro, raising the possibility that a modified B-box domain may compensate for its lack of a RING domain. SINA2 physically interacts with the nuclear protein CYCLIN-DEPENDENT KINASE G1 (CDKG1), which acts as a positive regulator of plant responses to abiotic stress. CDKG1 is expressed in multiple tissues and its expression increased in response to abscisic acid (ABA) and osmotic stress. Transgenic Arabidopsis plants that ectopically express CDKG1 exhibit increased tolerance to ABA and osmotic stress treatments during seed germination and cotyledon development, while the loss-of-function cdkg1 mutant plants show reduced tolerance to ABA and osmotic stress treatments. Moreover, CDKG1-dependent phosphorylation of SINA2 positively affects its E3 ubiquitin ligase activity.

CONCLUSIONS: Based on these results, we propose that CDKG1 modulates SINA2 ubiquitin ligase activity to regulate its effect on plant responses to ABA and osmotic stress.}, } @article {pmid30012093, year = {2018}, author = {Ganesamoorthy, D and Cao, MD and Duarte, T and Chen, W and Coin, L}, title = {GtTR: Bayesian estimation of absolute tandem repeat copy number using sequence capture and high throughput sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {267}, pmid = {30012093}, issn = {1471-2105}, support = {APP1052303//National Health and Medical Research Council/ ; }, abstract = {BACKGROUND: Tandem repeats comprise significant proportion of the human genome including coding and regulatory regions. They are highly prone to repeat number variation and nucleotide mutation due to their repetitive and unstable nature, making them a major source of genomic variation between individuals. Despite recent advances in high throughput sequencing, analysis of tandem repeats in the context of complex diseases is still hindered by technical limitations. We report a novel targeted sequencing approach, which allows simultaneous analysis of hundreds of repeats. We developed a Bayesian algorithm, namely - GtTR - which combines information from a reference long-read dataset with a short read counting approach to genotype tandem repeats at population scale. PCR sizing analysis was used for validation.

RESULTS: We used a PacBio long-read sequenced sample to generate a reference tandem repeat genotype dataset with on average 13% absolute deviation from PCR sizing results. Using this reference dataset GtTR generated estimates of VNTR copy number with accuracy within 95% high posterior density (HPD) intervals of 68 and 83% for capture sequence data and 200X WGS data respectively, improving to 87 and 94% with use of a PCR reference. We show that the genotype resolution increases as a function of depth, such that the median 95% HPD interval lies within 25, 14, 12 and 8% of the its midpoint copy number value for 30X, 200X WGS, 395X and 800X capture sequence data respectively. We validated nine targets by PCR sizing analysis and genotype estimates from sequencing results correlated well with PCR results.

CONCLUSIONS: The novel genotyping approach described here presents a new cost-effective method to explore previously unrecognized class of repeat variation in GWAS studies of complex diseases at the population level. Further improvements in accuracy can be obtained by improving accuracy of the reference dataset.}, } @article {pmid30012091, year = {2018}, author = {Ilacqua, AN and Price, JE and Graham, BN and Buccilli, MJ and McKellar, DR and Damer, CK}, title = {Cyclic AMP signaling in Dictyostelium promotes the translocation of the copine family of calcium-binding proteins to the plasma membrane.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {13}, pmid = {30012091}, issn = {1471-2121}, support = {R15 GM078089/GM/NIGMS NIH HHS/United States ; 2R15GM078089-02/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Calcium/metabolism ; Calcium-Binding Proteins/chemistry/*metabolism ; Carrier Proteins/chemistry/metabolism ; Cell Aggregation ; Cell Membrane/*metabolism ; Cyclic AMP/*metabolism ; Dictyostelium/*metabolism ; Green Fluorescent Proteins/metabolism ; Intracellular Membranes/metabolism ; Ionophores/metabolism ; Methanol ; Phospholipids/metabolism ; Protein Binding ; Protein Transport ; }, abstract = {BACKGROUND: Copines are calcium-dependent phospholipid-binding proteins found in many eukaryotic organisms and are thought to be involved in signaling pathways that regulate a wide variety of cellular processes. Copines are characterized by having two C2 domains at the N-terminus accompanied by an A domain at the C-terminus. Six copine genes have been identified in the Dictyostelium genome, cpnA - cpnF.

RESULTS: Independent cell lines expressing CpnA, CpnB, CpnC, CpnE, or CpnF tagged with green fluorescent protein (GFP) were created as tools to study copine protein membrane-binding and localization. In general, the GFP-tagged copine proteins appeared to localize to the cytoplasm in live cells. GFP-tagged CpnB, CpnC, and CpnF were also found in the nucleus. When cells were fixed or when live cells were treated with calcium ionophore, the GFP-tagged copine proteins were found associated with the plasma membrane and vesicular organelles. When starved Dictyostelium cells were stimulated with cAMP, which causes a transitory increase in calcium concentration, all of the copines translocated to the plasma membrane, but with varying magnitudes and on and off times, suggesting each of the copines has distinct calcium-sensitivities and/or membrane-binding properties. In vitro membrane binding assays showed that all of the GFP-tagged copines pelleted with cellular membranes in the presence of calcium; yet, each copine displayed distinct calcium-independent membrane-binding in the absence of calcium. A lipid overlay assay with purified GFP-tagged copine proteins was used to screen for specific phospholipid-binding targets. Similar to other proteins that contain C2 domains, GFP-tagged copines bound to a variety of acidic phospholipids. CpnA, CpnB, and CpnE bound strongly to PS, PI(4)P, and PI(4,5)P2, while CpnC and CpnF bound strongly to PI(4)P.

CONCLUSIONS: Our studies show that the Dictyostelium copines are soluble cytoplasmic and nuclear proteins that have the ability to bind intracellular membranes. Moreover, copines display different membrane-binding properties suggesting they play distinct roles in the cell. The transient translocation of copines to the plasma membrane in response to cAMP suggests copines may play a specific role in chemotaxis signaling.}, } @article {pmid30012089, year = {2018}, author = {Hong, SH and Kwon, JT and Kim, J and Jeong, J and Kim, J and Lee, S and Cho, C}, title = {Profiling of testis-specific long noncoding RNAs in mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {539}, pmid = {30012089}, issn = {1471-2164}, support = {NRF-2015R1A2A2A01005300),//National Research Foundation of Korea/ ; NRF 2013M3A9A7046297//National Research Foundation of Korea/ ; }, mesh = {Animals ; Cell Line ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Ontology ; Male ; Mice ; Open Reading Frames ; RNA, Long Noncoding/classification/*genetics/metabolism ; RNA, Messenger/genetics/metabolism ; Spermatogenesis/genetics ; Testis/cytology/*metabolism ; }, abstract = {BACKGROUND: Spermatogenesis, which is the complex and highly regulated process of producing haploid spermatozoa, involves testis-specific transcripts. Recent studies have discovered that long noncoding RNAs (lncRNAs) are novel regulatory molecules that play important roles in various biological processes. However, there has been no report on the comprehensive identification of testis-specific lncRNAs in mice.

RESULTS: We performed microarray analysis of transcripts from mouse brain, heart, kidney, liver and testis. We found that testis harbored the highest proportion of tissue-specific lncRNAs (11%; 1607 of 14,256). Testis also harbored the largest number of tissue-specific mRNAs among the examined tissues, but the proportion was lower than that of lncRNAs (7%; 1090 of 16,587). We categorized the testis-specific lncRNAs and found that a large portion corresponded to long intergenic ncRNAs (lincRNAs). Genomic analysis identified 250 protein-coding genes located near (≤ 10 kb) 194 of the loci encoding testis-specific lincRNAs. Gene ontology (GO) analysis showed that these protein-coding genes were enriched for transcriptional regulation-related terms. Analysis of male germ cell-related cell lines (F9, GC-1 and GC-2) revealed that some of the testis-specific lncRNAs were expressed in each of these cell lines. Finally, we arbitrarily selected 26 testis-specific lncRNAs and performed in vitro expression analysis. Our results revealed that all of them were expressed exclusively in the testis, and 23 of the 26 showed germ cell-specific expression.

CONCLUSION: This study provides a catalog of testis-specific lncRNAs and a basis for future investigation of the lncRNAs involved in spermatogenesis and testicular functions.}, } @article {pmid30012088, year = {2018}, author = {Okamura, Y and Kinoshita, K}, title = {Matataki: an ultrafast mRNA quantification method for large-scale reanalysis of RNA-Seq data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {266}, pmid = {30012088}, issn = {1471-2105}, support = {15H02773//Japan Society for the Promotion of Science/ ; }, abstract = {BACKGROUND: Data generated by RNA sequencing (RNA-Seq) is now accumulating in vast amounts in public repositories, especially for human and mouse genomes. Reanalyzing these data has emerged as a promising approach to identify gene modules or pathways. Although meta-analyses of gene expression data are frequently performed using microarray data, meta-analyses using RNA-Seq data are still rare. This lag is partly due to the limitations in reanalyzing RNA-Seq data, which requires extensive computational resources. Moreover, it is nearly impossible to calculate the gene expression levels of all samples in a public repository using currently available methods. Here, we propose a novel method, Matataki, for rapidly estimating gene expression levels from RNA-Seq data.

RESULTS: The proposed method uses k-mers that are unique to each gene for the mapping of fragments to genes. Since aligning fragments to reference sequences requires high computational costs, our method could reduce the calculation cost by focusing on k-mers that are unique to each gene and by skipping uninformative regions. Indeed, Matataki outperformed conventional methods with regards to speed while demonstrating sufficient accuracy.

CONCLUSIONS: The development of Matataki can overcome current limitations in reanalyzing RNA-Seq data toward improving the potential for discovering genes and pathways associated with disease at reduced computational cost. Thus, the main bottleneck of RNA-Seq analyses has shifted to achieving the decompression of sequenced data. The implementation of Matataki is available at https://github.com/informationsea/Matataki .}, } @article {pmid30012087, year = {2018}, author = {Yeganova, L and Kim, S and Balasanov, G and Wilbur, WJ}, title = {Discovering themes in biomedical literature using a projection-based algorithm.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {269}, pmid = {30012087}, issn = {1471-2105}, abstract = {BACKGROUND: The need to organize any large document collection in a manner that facilitates human comprehension has become crucial with the increasing volume of information available. Two common approaches to provide a broad overview of the information space are document clustering and topic modeling. Clustering aims to group documents or terms into meaningful clusters. Topic modeling, on the other hand, focuses on finding coherent keywords for describing topics appearing in a set of documents. In addition, there have been efforts for clustering documents and finding keywords simultaneously.

RESULTS: We present an algorithm to analyze document collections that is based on a notion of a theme, defined as a dual representation based on a set of documents and key terms. In this work, a novel vector space mechanism is proposed for computing themes. Starting with a single document, the theme algorithm treats terms and documents as explicit components, and iteratively uses each representation to refine the other until the theme is detected. The method heavily relies on an optimization routine that we refer to as the projection algorithm which, under specific conditions, is guaranteed to converge to the first singular vector of a data matrix. We apply our algorithm to a collection of about sixty thousand PubMed Ⓡ documents examining the subject of Single Nucleotide Polymorphism, evaluate the results and show the effectiveness and scalability of the proposed method.

CONCLUSIONS: This study presents a contribution on theoretical and algorithmic levels, as well as demonstrates the feasibility of the method for large scale applications. The evaluation of our system on benchmark datasets demonstrates that our method compares favorably with the current state-of-the-art methods in computing clusters of documents with coherent topic terms.}, } @article {pmid30012086, year = {2018}, author = {Jan, S and Alyemeni, MN and Wijaya, L and Alam, P and Siddique, KH and Ahmad, P}, title = {Interactive effect of 24-epibrassinolide and silicon alleviates cadmium stress via the modulation of antioxidant defense and glyoxalase systems and macronutrient content in Pisum sativum L. seedlings.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {146}, pmid = {30012086}, issn = {1471-2229}, abstract = {BACKGROUND: This study assessed the effects of 24-epibrassinolide (EBL, 10-7M) and silicon (2 mM) on the alleviation of cadmium (Cd, 150 mg L-1) toxicity in Pisum sativum L. seedlings via the modulation of growth, antioxidant defense, glyoxalase system, and nutrient uptake.

RESULTS: Shoot and root lengths declined by 46.43% and 52.78%, respectively, following Cd stress. Shoot and root dry weights also declined with Cd toxicity. Biochemical and physiological aspects exhibit significant decline including total chlorophyll (33.09%), carotenoid (51.51%), photosynthetic efficiency (32.60%), photochemical quenching (19.04%), leaf relative water content (40.18%), and gas exchange parameters (80.65%). However, EBL or Si supplementation alone or in combination modulates the previously mentioned parameters. Cadmium stress increased proline and glycine betaine (GB) contents by 4.37 and 2.41-fold, respectively. Exposure of plants to Cd stress increased the accumulation of H2O2, malondialdehyde content, electrolyte leakage, and methylglyoxal, which declined significantly with EBL and Si supplementation, both individually and in combination. Similarly, Cd stress adversely affected enzymatic and non-enzymatic antioxidants, but EBL and/or Si supplementation maintained antioxidant levels. Glyoxalase I (GlyI) accumulated after Cd stress and increased further with the application of EBL and Si. However, GlyII content declined after Cd stress but increased with supplementation of EBL and Si. Cadmium accumulation occurred in the following order: roots > shoots>leaves. Supplementation with EBL and Si, individually and in combination reduced Cd accumulation and enhanced the uptake of macronutrients and micronutrients in shoots and roots, which declined with Cd toxicity.

CONCLUSION: The application of 24-EBL and Si, individually and in combination, alleviated the adverse effects of Cd by improving growth, biochemical parameters, nutrient uptake, osmolyte accumulation, and the anti-oxidative defense and glyoxalase systems in Pisum sativum seedlings.}, } @article {pmid30011002, year = {2018}, author = {Choi, DH and An, SM and Yang, EC and Lee, H and Shim, J and Jeong, J and Noh, JH}, title = {Daily variation in the prokaryotic community during a spring bloom in shelf waters of the East China Sea.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, pmid = {30011002}, issn = {1574-6941}, abstract = {To understand prokaryotic responses during a spring bloom in offshore shelf waters, prokaryotic parameters were measured daily at a station located in the middle of the East China Sea over a six-week period from March 25 to May 19. The site experienced a phytoplankton bloom in late April, triggering changes in prokaryotic abundance and production after a lag of approximately one week. Before the bloom, changes in prokaryotic composition were small. Both during the bloom and in the post-bloom period, successive changes among bacterial groups were apparent. A SAR11 group became more dominant during the bloom period, and diverse groups belonging to the Flavobacteriia occurred dominantly during both the bloom and post-bloom periods. However, bacterial community changes at the species level during the bloom and post-bloom periods occurred rapidly in a time scale of a few days. Especially, NS5, NS4 and Formosa bacteria belonging to Flavobacteriia and bacteria belonging to Halieaceae and Arenicellaceae families of Gammaproteobacteria showed a successive pattern with large short-term variation during the period. The changes in prokaryotic composition were found to be related to phytoplankton biomass and composition, as well as seawater temperature and variations in nutrients.}, } @article {pmid30010964, year = {2018}, author = {Gutierrez, EA and Castiglione, GM and Morrow, JM and Schott, RK and Loureiro, LO and Lim, BK and Chang, BSW}, title = {Functional Shifts in Bat Dim-Light Visual Pigment Are Associated with Differing Echolocation Abilities and Reveal Molecular Adaptation to Photic-Limited Environments.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2422-2434}, doi = {10.1093/molbev/msy140}, pmid = {30010964}, issn = {1537-1719}, abstract = {Bats are excellent models for studying the molecular basis of sensory adaptation. In Chiroptera, a sensory trade-off has been proposed between the visual and auditory systems, though the extent of this association has yet to be fully examined. To investigate whether variation in visual performance is associated with echolocation, we experimentally assayed the dim-light visual pigment rhodopsin from bat species with differing echolocation abilities. While spectral tuning properties were similar among bats, we found that the rate of decay of their light-activated state was significantly slower in a nonecholocating bat relative to species that use distinct echolocation strategies, consistent with a sensory trade-off hypothesis. We also found that these rates of decay were remarkably slower compared with those of other mammals, likely indicating an adaptation to dim light. To examine whether functional changes in rhodopsin are associated with shifts in selection intensity upon bat Rh1 sequences, we implemented selection analyses using codon-based likelihood clade models. While no shifts in selection were identified in response to diverse echolocation abilities of bats, we detected a significant increase in the intensity of evolutionary constraint accompanying the diversification of Chiroptera. Taken together, this suggests that substitutions that modulate the stability of the light-activated rhodopsin state were likely maintained through intensified constraint after bats diversified, being finely tuned in response to novel sensory specializations. Our study demonstrates the power of combining experimental and computational approaches for investigating functional mechanisms underlying the evolution of complex sensory adaptations.}, } @article {pmid30010947, year = {2018}, author = {Ates, LS and Dippenaar, A and Sayes, F and Pawlik, A and Bouchier, C and Ma, L and Warren, RM and Sougakoff, W and Majlessi, L and van Heijst, JWJ and Brossier, F and Brosch, R}, title = {Unexpected Genomic and Phenotypic Diversity of Mycobacterium africanum Lineage 5 Affects Drug Resistance, Protein Secretion, and Immunogenicity.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1858-1874}, pmid = {30010947}, issn = {1759-6653}, mesh = {Adult ; Animals ; Bacterial Proteins/*metabolism ; Base Pairing/genetics ; Computational Biology ; Drug Resistance, Bacterial/drug effects/*genetics ; Female ; Genetic Markers ; *Genomics ; Genotype ; Humans ; Isoniazid/pharmacology ; Male ; Mice, Inbred C57BL ; Middle Aged ; Mycobacterium/drug effects/*genetics/*immunology/isolation & purification ; Phenotype ; *Phylogeny ; Sequence Deletion/genetics ; T-Lymphocytes/drug effects/immunology ; }, abstract = {Mycobacterium africanum consists of Lineages L5 and L6 of the Mycobacterium tuberculosis complex (MTBC) and causes human tuberculosis in specific regions of Western Africa, but is generally not transmitted in other parts of the world. Since M. africanum is evolutionarily closely placed between the globally dispersed Mycobacterium tuberculosis and animal-adapted MTBC-members, these lineages provide valuable insight into M. tuberculosis evolution. Here, we have collected 15 M. africanum L5 strains isolated in France over 4 decades. Illumina sequencing and phylogenomic analysis revealed a previously underappreciated diversity within L5, which consists of distinct sublineages. L5 strains caused relatively high levels of extrapulmonary tuberculosis and included multi- and extensively drug-resistant isolates, especially in the newly defined sublineage L5.2. The specific L5 sublineages also exhibit distinct phenotypic characteristics related to in vitro growth, protein secretion and in vivo immunogenicity. In particular, we identified a PE_PGRS and PPE-MPTR secretion defect specific for sublineage L5.2, which was independent of PPE38. Furthermore, L5 isolates were able to efficiently secrete and induce immune responses against ESX-1 substrates contrary to previous predictions. These phenotypes of Type VII protein secretion and immunogenicity provide valuable information to better link genome sequences to phenotypic traits and thereby understand the evolution of the MTBC.}, } @article {pmid30010915, year = {2018}, author = {Lange, JD and Pool, JE}, title = {Impacts of Recurrent Hitchhiking on Divergence and Demographic Inference in Drosophila.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1882-1891}, pmid = {30010915}, issn = {1759-6653}, support = {T32 GM007133/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Computer Simulation ; Demography ; Drosophila melanogaster/*genetics ; *Genetic Variation ; Models, Genetic ; Population Density ; *Selection, Genetic ; }, abstract = {In species with large population sizes such as Drosophila, natural selection may have substantial effects on genetic diversity and divergence. However, the implications of this widespread nonneutrality for standard population genetic assumptions and practices remain poorly resolved. Here, we assess the consequences of recurrent hitchhiking (RHH), in which selective sweeps occur at a given rate randomly across the genome. We use forward simulations to examine two published RHH models for D. melanogaster, reflecting relatively common/weak and rare/strong selection. We find that unlike the rare/strong RHH model, the common/weak model entails a slight degree of Hill-Robertson interference in high recombination regions. We also find that the common/weak RHH model is more consistent with our genome-wide estimate of the proportion of substitutions fixed by natural selection between D. melanogaster and D. simulans (19%). Finally, we examine how these models of RHH might bias demographic inference. We find that these RHH scenarios can bias demographic parameter estimation, but such biases are weaker for parameters relating recently diverged populations, and for the common/weak RHH model in general. Thus, even for species with important genome-wide impacts of selective sweeps, neutralist demographic inference can have some utility in understanding the histories of recently diverged populations.}, } @article {pmid30010893, year = {2018}, author = {Stibal, M and Jacobsen, CS and Häggblom, MM}, title = {Editorial: Polar and Alpine Microbiology.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy136}, pmid = {30010893}, issn = {1574-6941}, } @article {pmid30010866, year = {2018}, author = {Godfroid, M and Dagan, T and Kupczok, A}, title = {Recombination Signal in Mycobacterium tuberculosis Stems from Reference-guided Assemblies and Alignment Artefacts.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1920-1926}, pmid = {30010866}, issn = {1759-6653}, support = {281357//European Research Council/International ; }, mesh = {*Artifacts ; Genome, Bacterial ; Mycobacterium tuberculosis/*genetics ; Phylogeny ; *Recombination, Genetic ; Reference Standards ; *Sequence Alignment ; }, abstract = {DNA acquisition via genetic recombination is considered advantageous as it has the potential to bring together beneficial mutations that emerge independently within a population. Furthermore, recombination is considered to contribute to the maintenance of genome stability by purging slightly deleterious mutations. The prevalence of recombination differs among prokaryotic species and depends on the accessibility of DNA transfer mechanisms. An exceptional example is the human pathogen Mycobacterium tuberculosis (MTB) where no clear transfer mechanisms have been so far characterized and the presence of recombination is questioned. Here, we analyze completely assembled MTB genomes in search for evidence of recombination. We find that putative recombination events are enriched in strains reconstructed by reference-guided assembly and in regions with unreliable alignments. In addition, assembly and alignment artefacts introduce phylogenetic signals that are conflicting the established MTB phylogeny. Our results reveal that the so far reported recombination events in MTB are likely to stem from methodological artefacts. We conclude that no reliable signal of recombination is observed in the currently available MTB genomes. Moreover, our study demonstrates the limitations of reference-guided genome assembly for phylogenetic reconstructions. Rigorously de novo assembled genomes of high quality are mandatory in order to distinguish true evolutionary signal from noise, in particular for low diversity species such as MTB.}, } @article {pmid30010859, year = {2018}, author = {Macías-Rodríguez, L and Guzmán-Gómez, A and García-Juárez, P and Contreras-Cornejo, HA}, title = {Trichoderma atroviride promotes tomato development and alters the root exudation of carbohydrates, which stimulates fungal growth and the biocontrol of the phytopathogen Phytophthora cinnamomi in a tripartite interaction system.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy137}, pmid = {30010859}, issn = {1574-6941}, abstract = {Several species of Trichoderma promote plant growth and help in defense against root pathogens. The role of root-exuded carbohydrates as chemo-attractive stimuli for Trichoderma colonization is attracting considerable interest. In this project, we studied the interaction between Trichoderma atroviride and tomato (Lycopersicon esculentum L. cv. Río Grande) plants in two different stages, before and during root colonization. In addition, the biocontrol capacity of T. atroviride against the phytopathogen Phytophthora cinnamomi in a tripartite interaction system was examined. We found that the beneficial effects of T. atroviride on plant growth were fine-tuned depending on the progress of interaction. Interestingly, the composition of the carbohydrate exudate from plants interacting with T. atroviride was different from that produced by other treatments and probably provided a nutritional source for the fungus. Particularly, sucrose was found only during root colonization by the fungus. Our data show that root-derived sugars enabled a higher Trichoderma growth rate, and that, in the tripartite interaction system with P. cinnamomi, the fungus competes for space and available soil nutrients more efficiently than P. cinnamomi, thereby antagonizing the growth of the phytopathogen.}, } @article {pmid30010841, year = {2018}, author = {Beattie, RE and Walsh, M and Cruz, MC and McAliley, LR and Dodgen, L and Zheng, W and Hristova, KR}, title = {Agricultural contamination impacts antibiotic resistance gene abundances in river bed sediment temporally.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy131}, pmid = {30010841}, issn = {1574-6941}, abstract = {Kewaunee County, Wisconsin is an agricultural area dominated by concentrated animal feeding operations and manure fertilized cropland. The objective of this study was to characterize chemical and antibiotic resistance gene (ARG) profiles of 20 surface water locations in Kewaunee County to better understand relationships between agricultural contamination and ARG abundance over one year. Surface water (n = 101) and bed sediment (n = 93) were collected from 20 sites during five timepoints between July 2016 and May 2017. Samples were analyzed for six genes (erm(B), tet(W), sul1, qnrA, intI1 and 16S rRNA) and water chemistry and pollution indicators. qnrA, intI1 and sul1 genes in surface water were significantly higher than erm(B) and tet(W); however, no difference was present in sediment samples. Redundancy analysis identified positive correlations of nitrate, Escherichia coli, and coliforms with tet(W) and intI1 genes in sediment and intI1, sul1 and tet(W) genes in water. Temporal patterns of ARG abundance were identified with significantly higher gene abundances found in sediment during Kewaunee County's manure fertilization period; however, surface water patterns were not distinct. Together, these results suggest Kewaunee County sediments serve as a site of accumulation for non-point source agricultural pollution and ARGs on a temporal scale associated with manure fertilization.}, } @article {pmid30010752, year = {2018}, author = {Parker, DJ and Wiberg, RAW and Trivedi, U and Tyukmaeva, VI and Gharbi, K and Butlin, RK and Hoikkala, A and Kankare, M and Ritchie, MG}, title = {Inter and Intraspecific Genomic Divergence in Drosophila montana Shows Evidence for Cold Adaptation.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {2086-2101}, pmid = {30010752}, issn = {1759-6653}, mesh = {Acclimatization ; Animals ; Cold Temperature ; Diapause ; Drosophila/*classification/*genetics/physiology ; Genome, Insect ; Molecular Sequence Annotation ; Phylogeny ; }, abstract = {The genomes of species that are ecological specialists will likely contain signatures of genomic adaptation to their niche. However, distinguishing genes related to ecological specialism from other sources of selection and more random changes is a challenge. Here, we describe the genome of Drosophila montana, which is the most extremely cold-adapted Drosophila species known. We use branch tests to identify genes showing accelerated divergence in contrasts between cold- and warm-adapted species and identify about 250 genes that show differences, possibly driven by a lower synonymous substitution rate in cold-adapted species. We also look for evidence of accelerated divergence between D. montana and D. virilis, a previously sequenced relative, but do not find strong evidence for divergent selection on coding sequence variation. Divergent genes are involved in a variety of functions, including cuticular and olfactory processes. Finally, we also resequenced three populations of D. montana from across its ecological and geographic range. Outlier loci were more likely to be found on the X chromosome and there was a greater than expected overlap between population outliers and those genes implicated in cold adaptation between Drosophila species, implying some continuity of selective process at these different evolutionary scales.}, } @article {pmid30010747, year = {2018}, author = {Nusbaum, DJ and Sun, F and Ren, J and Zhu, Z and Ramsy, N and Pervolarakis, N and Kunde, S and England, W and Gao, B and Fiehn, O and Michail, S and Whiteson, K}, title = {Gut microbial and metabolomic profiles after fecal microbiota transplantation in pediatric ulcerative colitis patients.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy133}, pmid = {30010747}, issn = {1574-6941}, support = {R01 HD081197/HD/NICHD NIH HHS/United States ; T32 EB009418/EB/NIBIB NIH HHS/United States ; }, abstract = {Ulcerative colitis is a chronic inflammatory disease of the colon that carries a significant disease burden in children. Therefore, new therapeutic approaches are being explored to help children living with this disease. Fecal microbiota transplantation (FMT) has been successful in some children with ulcerative colitis. However, the mechanism of its therapeutic effect in this patient population is not well understood. To characterize changes in gut microbial and metabolomic profiles after FMT, we performed 16S rRNA gene sequencing, shotgun metagenomic sequencing, virome analysis and untargeted metabolomics by gas chromatography-time of flight-mass spectrometry on stool samples collected before and after FMT from four children with ulcerative colitis who responded to this treatment. Alpha diversity of the gut microbiota increased after intervention, with species richness rising from 251 (S.D. 125) to 358 (S.D. 27). In responders, the mean relative abundance of bacteria in the class Clostridia shifted toward donor levels, increasing from 33% (S.D. 11%) to 54% (S.D. 16%). Patient metabolomic and viromic profiles exhibited a similar but less pronounced shift toward donor profiles after FMT. The fecal concentrations of several metabolites were altered after FMT, correlating with clinical improvement. Larger studies using a similar multi-omics approach may suggest novel strategies for the treatment of pediatric ulcerative colitis.}, } @article {pmid30010743, year = {2018}, author = {Taylor, JD and Bird, KE and Widdicome, CE and Cunliffe, M}, title = {Active bacterioplankton community response to dissolved 'free' deoxyribonucleic acid (dDNA) in surface coastal marine waters.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {10}, pages = {}, doi = {10.1093/femsec/fiy132}, pmid = {30010743}, issn = {1574-6941}, abstract = {Seawater contains dissolved 'free' DNA (dDNA) that is part of a larger <0.2 µm pool of DNA (D-DNA) including viruses and uncharacterised bound DNA. Previous studies have shown that bacterioplankton readily degrade dDNA, and culture-based approaches have identified several potential dDNA-utilising taxa. This study characterised the seasonal variation in D-DNA concentrations at Station L4, a coastal marine observatory in the Western English Channel, and linked changes in concentration to cognate physicochemical and biological factors. The impact of dDNA addition on active bacterioplankton communities at Station L4 was then determined using 16S rRNA high-throughput sequencing and RNA Stable Isotope Probing (RNA SIP) with 13C-labelled diatom-derived dDNA. Compared to other major bacterioplankton orders, the Rhodobacterales actively responded to dDNA additions in amended microcosms and RNA SIP identified two Rhodobacterales populations most closely associated with the genera Halocynthiibacter and Sulfitobacter that assimilated the 13C-labelled dDNA. Here we demonstrate that dDNA is a source of dissolved organic carbon for some members of the major bacterioplankton group the Marine Roseobacter Clade. This study enhances our understanding of roles of specific bacterioplankton taxa in dissolved organic matter cycling in coastal waters with potential implications for nitrogen and phosphorus regeneration processes.}, } @article {pmid30010741, year = {2018}, author = {Zhang, Y and Jewett, C and Gilley, J and Bartelt-Hunt, SL and Snow, DD and Hodges, L and Li, X}, title = {Microbial Communities in the Rhizosphere and the Root of Lettuce as Affected by Salmonella-Contaminated Irrigation Water.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy135}, pmid = {30010741}, issn = {1574-6941}, abstract = {Reclaimed wastewater is increasingly used as a source of irrigation water in croplands. The enteric pathogens in reclaimed wastewater may accumulate in soil and plants and cause food safety concerns. The objective of this study was to determine the effects of irrigation water containing Salmonella on the microbial communities in the rhizosphere and in the root of lettuce. The effects were also examined with three variables (soil texture, lettuce cultivar, and harvest time) in a factorial design. Analyses on the 16S rRNA gene sequences show that the microbial communities in the root were significantly different from those in the rhizosphere, although ∼80% of the microbes in the root originated from the rhizosphere. Salmonella in irrigation water significantly altered the structure of the microbial community in the rhizosphere, but not in the root. Salmonella internalized in lettuce root was observed when contaminated water was used for irrigation. Compared to lettuce cultivar and harvest time, soil texture played a more significant role in shaping the bacterial communities in rhizosphere and root. Results from the study could advance the understanding about the long-term impacts of reclaimed wastewater as a source of irrigation water on the microbiota associated with leafy green vegetables.}, } @article {pmid30010529, year = {2018}, author = {Mu, S and Zhao, Q and Zhao, J and Cao, T and Zhao, X and Guo, X and Li, Y and Xiang, W and Wang, X}, title = {Sphaerisporangium rhizosphaerae sp. nov., an actinomycete isolated from the rhizosphere soil of a rubber tree (Hevea brasiliensis Muell. Arg).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2860-2865}, doi = {10.1099/ijsem.0.002912}, pmid = {30010529}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Hevea/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, designated strain NEAU-mq3T, was isolated from the rhizosphere soil of a rubber tree (Hevea brasiliensis Muell. Arg) collected from Xianglu Mountain in Heilongjiang Province, north-east China, and characterized by using a polyphasic approach. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that the organism should be assigned to the genus Sphaerisporangium and that it forms a monophyletic clade with its closest relatives 'Sphaerisporangium dianthi' NEAU-CY18T (99.2 % 16S rRNA gene sequence similarity) and Sphaerisporangium cinnabarinum JCM 3291T (98.8 %). Morphological and chemotaxonomic properties of strain NEAU-mq3T were also consistent with the description of the genus Sphaerisporangium. The whole-cell sugars were madurose, mannose, ribose and glucose. The menaquinones were MK-9(H2), MK-9(H4), MK-9(H0) and MK-9(H6). The diagnostic diamino acid of the peptidoglycan was meso-diaminopimelic acid. The phospholipid profile consisted of diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol mannoside, an unidentified polar lipid and an unidentified phospholipid. The major fatty acids were identified as iso-C16 : 0, 10-methyl C17 : 0, C16 : 1ω7c and C17 : 1ω7c. DNA-DNA hybridization experiments and phenotypic tests were carried out between strain NEAU-mq3T and its most closely related strains, which further clarified their relatedness and demonstrated that NEAU-mq3T could be distinguished from these strains. Therefore, it is concluded that strain NEAU-mq3T represents a novel species of the genus Sphaerisporangium, for which the name Sphaerisporangium rhizosphaerae sp. nov. is proposed. The type strain is NEAU-mq3T (=CGMCC 4.7429T=JCM 32389T).}, } @article {pmid30010528, year = {2018}, author = {Xue, H and Piao, CG and Wang, XZ and Lin, CL and Guo, MW and Li, Y}, title = {Sphingomonas aeria sp. nov., isolated from air.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2866-2871}, doi = {10.1099/ijsem.0.002910}, pmid = {30010528}, issn = {1466-5034}, mesh = {*Air Microbiology ; Bacterial Typing Techniques ; Base Composition ; Beijing ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/analogs & derivatives/chemistry ; Sphingomonas/*classification/genetics/isolation & purification ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-negative, aerobic, non-spore-forming, non-motile, yellow-pigmented and rod-shaped bacterial strain, designated B093034T, was isolated from air at the foot of Xiangshan mountain, located in Beijing, China. Cells of strain B093034T were oxidase-negative and catalase-positive. Growth was observed at 4-41 °C, at pH 4.5-10.0 and at 0-7 % (w/v) NaCl. The isolate contained Q-10 as the predominant isoprenoid quinone, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0 and C14 : 02-OH as the major fatty acids, sym-homospermidine as the major polyamine, and sphingoglycolipid, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, diphosphatidylglycerol, aminolipid, two unidentified phospholipids and three unidentified polar lipids as the polar lipids. The DNA G+C content was 67.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain B093034T grouped with members of the genus Sphingomonas and was closely related to Sphingomonas sanguinis IFO 13937T (96.49 % similarity), Sphingomonas pseudosanguinis G1-2T (96.37 %), Sphingomonas ginsenosidimutansGsoil 1429T (95.99 %) and Sphingomonas endophytica YIM 65583T (95.78 %). On the basis of the polyphasic evidence presented here, strain B093034T represents a novel species of the genus Sphingomonas, for which the name Sphingomonasaeria sp. nov. is proposed. The type strain is B093034T (=CFCC 13949T=LMG 30133T).}, } @article {pmid30010527, year = {2018}, author = {Wang, C and Han, JR and Liu, CL and Du, ZJ}, title = {Winogradskyella tangerina sp. nov., a member of the Flavobacteriaceae isolated from coastal sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2832-2837}, doi = {10.1099/ijsem.0.002908}, pmid = {30010527}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped bacterium (designated strain M1309T), with slow gliding motility, was isolated from marine sediment obtained off the coast of Weihai, PR China. The growth of M1309T was observed at 16-42 °C (optimum, 37 °C) and pH 6.5-8.0 (optimum, 7.0-7.5) in the presence of 2.0-6.0 % (w/v) NaCl (optimum, 2.0-3.0 %). Phylogenetic analyses based on the 16S rRNA gene sequence revealed that the strain represented a member of the genus Winogradskyella. M1309T exhibited the highest 16S rRNA gene sequence similarity, of 95.5 %, to Winogradskyella poriferorum JCM 12885T. Chemotaxonomic analysis revealed that the sole respiratory quinone was menaquinone 6 (MK-6) and the major fatty acids included iso-C15 : 0, iso-C15 : 1G and iso-C17 : 0 3-OH. The major polar lipids included phosphatidylethanolamine, two aminolipids, and three unidentified lipids. The DNA G+C content of the strain was 36.1 mol%. On the basis of phenotypic distinctiveness and phylogenetic divergence, strain M1309T is considered to represent a novel species of the genus Winogradskyella, for which the name Winogradskyella tangerina sp. nov. is proposed. The type strain is M1309T (=KCTC 52896T=MCCC 1K03310T).}, } @article {pmid30010526, year = {2018}, author = {Li, FN and Liao, S and Guo, M and Tuo, L and Yan, X and Li, W and Jin, T and Lee, SM and Sun, CH}, title = {Mangrovicella endophytica gen. nov., sp. nov., a new member of the family Aurantimonadaceae isolated from Aegiceras corniculatum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2838-2845}, doi = {10.1099/ijsem.0.002907}, pmid = {30010526}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Plant Bark/microbiology ; Primulaceae/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative, aerobic, motile and short-rod-shaped bacterium, designated strain 5T4P-12-1T, was isolated from a piece of surface-sterilized bark of Aegiceras corniculatum collected from Cotai Ecological Zones in Macao, China and tested by a polyphasic approach to clarify its taxonomic position. Strain 5T4P-12-1T grew optimally with 0-1 % (w/v) NaCl at 30 °C and at pH 7.0-8.0. The 16S rRNA gene sequence of strain 5T4P-12-1T had the highest similarity (96.7 %) to Aureimonas altamirensis DSM 21988T. Phylogenic analysis based on 16S rRNA gene sequences and coding sequences of 98 protein clusters showed that the strain represented a novel genus of the family Aurantimonadaceae. The predominant quinone system of strain 5T4P-12-1T was ubiquinone 10. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylmethylethanolamine, an unidentified aminophospholipid, three unidentified aminolipids, three unidentified phospholipids and three unidentified lipids. The major fatty acids (>10 % of total fatty acids) were C18 : 1ω7c (55.4 %) and C18 : 1 2-OH (15.6 %). The DNA G+C content of strain 5T4P-12-1T was 66.5 mol%. Based on the phylogenic, phenotypic and chemotaxonomic features, strain 5T4P-12-1T is considered to represent a novel species of a new genus in the family Aurantimonadaceae, for which the name Mangrovicella endophytica gen. nov., sp. nov. is proposed. The type strain is 5T4P-12-1T (=KCTC 62053T=CGMCC 1.16279 T).}, } @article {pmid30010525, year = {2018}, author = {Kim, HJ and Lee, HJ and Lim, B and Kim, E and Kim, HY and Suh, M and Hur, M}, title = {Lactobacillus terrae sp. nov., a novel species isolated from soil samples in the Republic of Korea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2906-2911}, doi = {10.1099/ijsem.0.002918}, pmid = {30010525}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lactobacillus/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel strain, designated NIBRBAC000499792T, was isolated from a soil sample collected at Jukgye, Dongnam, Cheonan, Republic of Korea. Cells were Gram-positive, non-motile, non-spore-forming, rod-shaped, oxidase-negative and catalase-negative. Colonies grown on de Man, Rogosa and Sharpe agar were white, circular, raised and entire. Analysis of the 16S rRNA gene sequence analysis revealed that strain NIBRBAC000499792T belongs to the genus Lactobacillus (family Lactobacillaceae) and is most closely related to Lactobacillus nodensis DSM 19682T (96.1 % similarity) and Lactobacillus tucceti KCTC 21005T (96.7 %). The results of DNA-DNA hybridization experiments demonstrated that strain NIBRBAC000499792T represents a novel species. Major fatty acids are C18 : 1ω9c, C16 : 0 and unidentified 18.846 and/or C19 : 1ω6c and/or C19 : 0cyclo. The predominant respiratory quinones are menaquinone-8 and menaquinone-9. The major polar lipids are phosphatidylglycerol and diphosphatidylglycerol. The minor polar lipids are one unidentified aminophospholipid, one unidentified phospholipid, and four unidentified lipids. Next-generation sequencing analysis of strain NIBRBAC000499792T indicated that the total genome size was 1 548 794 bp with a G+C content of 33.1 mol%, 1586 coding sequences, 50 tRNAs and nine rRNAs. The most closely related genomes belonged to Lactobacillus species. Most metabolic pathways were related to carbon metabolism and carbon fixation. Based on this polyphasic analysis, strain NIBRBAC000499792T represents a novel species of the genus Lactobacillus, for which the name Lactobacillus terrae sp. nov. is proposed, with the type strain NIBRBAC000499792T (=KCTC 21093T=JCM 32269T).}, } @article {pmid30010524, year = {2018}, author = {Nouioui, I and Ghodhbane-Gtari, F and Rhode, M and Sangal, V and Klenk, HP and Gtari, M}, title = {Frankia irregularis sp. nov., an actinobacterium unable to nodulate its original host, Casuarina equisetifolia, but effectively nodulates members of the actinorhizal Rhamnales.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2883-2914}, doi = {10.1099/ijsem.0.002914}, pmid = {30010524}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Frankia/*classification/genetics/isolation & purification ; Guadeloupe ; Magnoliopsida/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; *Plant Root Nodulation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Symbiosis ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A red pigmented actinobacterium designated G2T, forming extremely branched vegetative hyphae, vesicles and mutilocular sporangia, was isolated from Casuarina equisetifolia nodules. The strain failed to nodulate its original host plant but effectively nodulated members of actinorhizal Rhamnales. The taxonomic position of G2T was determined using a polyphasic approach. The peptidoglycan of the strain contained meso-diaminopimelic acid as diagnostic diamino acid, galactose, glucose, mannose, rhamnose, ribose and xylose. The polar lipid pattern consisted of phosphatidylinositol (PI), diphosphatidylglycerol (DPG), glycophospholipids (GPL1-2), phosphatidylglycerol (PG), aminophospholipid (APL) and unknown lipids (L). The predominant menaquinones were MK-9 (H4) and MK-9 (H6) while the major fatty acids were iso-C16 : 0, C17 : 1ω8c and C15 : 0. The size of the genome of G2T was 9.5 Mb and digital DNA G+C content was 70.9 %. The 16S rRNA gene showed 97.4-99.5 % sequence identity with the type strains of species of the genus Frankia. Digital DNA -DNA hybridisation (dDDH) values between G2T and its nearest phylogenetic neighbours Frankia elaeagniand Frankia discariaewere below the threshold of 70 %. On the basis of these results, strain G2T (=DSM 45899T=CECT 9038T) is proposed to represent the type strain of a novel species Frankia irregularis sp. nov.}, } @article {pmid30010523, year = {2018}, author = {Yin, Q and Zhang, L and Song, ZM and Wu, Y and Hu, ZL and Zhang, XH and Zhang, Y and Yu, M and Xu, Y}, title = {Euzebya rosea sp. nov., a rare actinobacterium isolated from the East China Sea and analysis of two genome sequences in the genus Euzebya.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2900-2905}, doi = {10.1099/ijsem.0.002917}, pmid = {30010523}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Rare Actinobacteria, known as non-Streptomyces, hold great potential to produce new bioactive compounds for drug development. A strain designated DSW09T, which belongs those rare Actinobacteria, was isolated from surface seawater of the East China Sea. The cells were aerobic, Gram-positive, non-motile, non-spore-forming and rod-shaped (0.4 µm wide and 1.5-4.0 µm long). The closest relative was Euzebya tangerina F10T (96.46 % of 16S rRNA gene similarity). Cell growth occurred at 15-45 °C (optimum, 25-30 °C), at pH 6.0-9.0 (pH 6.0-7.0) and at NaCl concentrations of 0.5-5.0 % (w/v; 1.0-4.0 %). The major cellular fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C15 : 0iso 2OH), C17 : 1ω8c and C16 : 0. The predominant polar lipid was diphosphatidylglycerol. The predominant menaquinone was MK-9(H4). The cell-wall peptidoglycan was A1 γ-type, containing meso-DPA. The major cell-wall sugars were rhamnose and ribose. The genome size was 5 509 297 bp with a 71.29 mol% G+C content for strain DSW09T, while 4 781 440 bp with a 68.87 mol% G+C content for E. tangerina F10T. The average nucleotide identity and digital DNA-DNA hybridization values between strain DSW09T and E. tangerina F10T were 73.44 % and 16.43 %, respectively. Based on phylogenetic, phenotypic, chemotaxonomic evidence and genomic analyses, strain DSW09T is a novel species of genus Euzebya, for which the name Euzebya rosea sp. nov. is proposed. The type strain is DSW09T (=DMS 104446T=MCCC 1K03290T).}, } @article {pmid30010522, year = {2018}, author = {Navarro-Torre, S and Carro, L and Rodríguez-Llorente, ID and Pajuelo, E and Caviedes, MÁ and Igual, JM and Redondo-Gómez, S and Camacho, M and Klenk, HP and Montero-Calasanz, MDC}, title = {Kushneria phyllosphaerae sp. nov. and Kushneria endophytica sp. nov., plant growth promoting endophytes isolated from the halophyte plant Arthrocnemum macrostachyum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2800-2806}, doi = {10.1099/ijsem.0.002897}, pmid = {30010522}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chenopodiaceae/*microbiology ; DNA, Bacterial/genetics ; Endophytes/classification/isolation & purification ; Fatty Acids/chemistry ; Halomonadaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salt-Tolerant Plants/*microbiology ; Sequence Analysis, DNA ; Spain ; Ubiquinone/chemistry ; }, abstract = {Two endophytic bacteria (EAod3T and EAod7T) were isolated from the aerial part of plants of Arthrocnemum macrostachyum growing in the Odiel marshes (Huelva, Spain). Phylogenetic analysis based on 16S rRNA gene sequences indicated their affiliation to the genus Kushneria. 16S rRNA gene sequences of strains EAod3T and EAod7T showed the highest similarity to Kushneria marisflavi DSM 15357T (99.0 and 97.6 %, respectively). Digital DNA-DNA hybridization studies between the draft genomes of strain EAod3T and K. marisflavi DSM 15357T corresponded to 28.5 % confirming the novel lineage of strain EAod3T in the genus Kushneria. Cells of both strains were Gram-staining-negative, aerobic and motile rods able to grow at 4-37 °C, at pH 5.0-8.0 and tolerate 0.5-25 % NaCl (w/v). They presented ubiquinone Q9 and C16 : 0, C16 : 1ω7c/C16 : 1ω6c and C18 : 1ω7c as the major fatty acids. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Based on the phenotypic and phylogenetic results, strains EAod3T (=CECT 9073T=LMG 29856T) and EAod7T (=CECT 9075T=LMG 29858T) are proposed as new representatives of the genus Kushneria, and the proposed names are Kushneria phyllosphaerae sp. nov. and Kushneria endophytica sp. nov., respectively. The whole genome sequence of strain EAod3T has a total length of 3.8 Mbp and a G+C content of 59.3 mol%.}, } @article {pmid30009397, year = {2018}, author = {Sanger, TJ and Rajakumar, R}, title = {How a growing organismal perspective is adding new depth to integrative studies of morphological evolution.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12442}, pmid = {30009397}, issn = {1469-185X}, abstract = {Over the past half century, the field of Evolutionary Developmental Biology, or Evo-devo, has integrated diverse fields of biology into a more synthetic understanding of morphological diversity. This has resulted in numerous insights into how development can evolve and reciprocally influence morphological evolution, as well as generated several novel theoretical areas. Although comparative by default, there remains a great gap in our understanding of adaptive morphological diversification and how developmental mechanisms influence the shape and pattern of phenotypic variation. Herein we highlight areas of research that are in the process of filling this void, and areas, if investigated more fully, that will add new insights into the diversification of morphology. At the centre of our discussion is an explicit awareness of organismal biology. Here we discuss an organismal framework that is supported by three distinct pillars. First, there is a need for Evo-devo to adopt a high-resolution phylogenetic approach in the study of morphological variation and its developmental underpinnings. Secondly, we propose that to understand the dynamic nature of morphological evolution, investigators need to give more explicit attention to the processes that generate evolutionarily relevant variation at the population level. Finally, we emphasize the need to address more thoroughly the processes that structure variation at micro- and macroevolutionary scales including modularity, morphological integration, constraint, and plasticity. We illustrate the power of these three pillars using numerous examples from both invertebrates and vertebrates to emphasize that many of these approaches are already present within the field, but have yet to be formally integrated into many research programs. We feel that the most exciting new insights will come where the traditional experimental approaches to Evo-devo are integrated more thoroughly with the principles of this organismal framework.}, } @article {pmid30009337, year = {2018}, author = {Rana, M and Dash, AK and Ponnusamy, K and Tyagi, RK}, title = {Nuclear localization signal region in nuclear receptor PXR governs the receptor association with mitotic chromatin.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9583-2}, pmid = {30009337}, issn = {1573-6849}, support = {project ID 25//UPE-II (University with Potential for Excellence phase II)/ ; F.No. 41-1294/2012(SR)//UGC (University Grants Commission)/ ; F.No. 3-17/2015/DRS II (SAP-II)//UGC-SAP (University Grants Commission-Special Assistance Programme)/ ; F.No. 63/9/2010-BMS//ICMR-CAR (Indian Council of Medical Research-Centre for Advanced Research)/ ; PAC-JNU-DST-PURSE-462 (Phase-II)//DST-PURSE (Department of Science & Technology-Promotion of University Research and Scientific Excellence)/ ; }, abstract = {In recent years, some transcription factors have been observed to remain associated with mitotic chromatin. Based on these observations, it is suggested that these chromatin-bound transcription factors may serve as 'epigenetic marks' for transmission of pattern of gene expression from progenitor to progeny cells. In this context, our laboratory has reported that nuclear receptor PXR, a master regulator of xenobiotic metabolism, remains constitutively associated with mitotic chromatin. However, the region responsible for this interaction with chromatin remained unknown. In this study, we have shown, for the first time, that mitotic chromatin association of this factor is mediated by the combined action of two zinc fingers present in the DNA-binding domain of PXR. Overall, the nuclear localization signal (NLS) region appears to play a major role in this interaction with mitotic chromatin. Also, we have identified a sub-region of 11 amino acid residues within NLS region of PXR (R66-76R) essential for receptor interaction with the mitotic chromatin. Interestingly, this minimal region is sequence-specific and independent of its basic charge. We have termed this minimal sub-region as 'mitotic chromatin binding-determining region' (MCBR). It is suggested that this receptor region is essential for activation of its target genes. Additionally, we have shown that PXR remains associated with the everted repeat (ER6) region of its major target gene, CYP3A4 promoter during mitosis implying its suggested role in 'gene bookmarking'.}, } @article {pmid30008993, year = {2018}, author = {Guzzo, MM and Van Leeuwen, TE and Hollins, J and Koeck, B and Newton, M and Webber, DM and Smith, FI and Bailey, DM and Killen, SS}, title = {Field testing a novel high residence positioning system for monitoring the fine-scale movements of aquatic organisms.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {6}, pages = {1478-1488}, pmid = {30008993}, issn = {2041-210X}, abstract = {Acoustic telemetry is an important tool for studying the behaviour of aquatic organisms in the wild.VEMCO high residence (HR) tags and receivers are a recent introduction in the field of acoustic telemetry and can be paired with existing algorithms (e.g. VEMCO positioning system [VPS]) to obtain high-resolution two-dimensional positioning data.Here, we present results of the first documented field test of a VPS composed of HR receivers (hereafter, HR-VPS). We performed a series of stationary and moving trials with HR tags (mean HR transmission period = 1.5 s) to evaluate the precision, accuracy and temporal capabilities of this positioning technology. In addition, we present a sample of data obtained for five European perch Perca fluviatilis implanted with HR tags (mean HR transmission period = 4 s) to illustrate how this technology can estimate the fine-scale behaviour of aquatic animals.Accuracy and precision estimates (median [5th-95th percentile]) of HR-VPS positions for all stationary trials were 5.6 m (4.2-10.8 m) and 0.1 m (0.02-0.07 m), respectively, and depended on the location of tags within the receiver array. In moving tests, tracks generated by HR-VPS closely mimicked those produced by a handheld GPS held over the tag, but these differed in location by an average of ≈9 m.We found that estimates of animal speed and distance travelled for perch declined when positional data for acoustically tagged perch were thinned to mimic longer transmission periods. These data also revealed a trade-off between capturing real nonlinear animal movements and the inclusion of positioning error.Our results suggested that HR-VPS can provide more representative estimates of movement metrics and offer an advancement for studying fine-scale movements of aquatic organisms, but high-precision survey techniques may be needed to test these systems.}, } @article {pmid30008988, year = {2018}, author = {Epstein, SC and Charkoudian, LK and Medema, MH}, title = {A standardized workflow for submitting data to the Minimum Information about a Biosynthetic Gene cluster (MIBiG) repository: prospects for research-based educational experiences.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {16}, pmid = {30008988}, issn = {1944-3277}, abstract = {Microorganisms utilize complex enzymatic pathways to biosynthesize structurally complex and pharmacologically relevant molecules. These pathways are encoded by gene clusters and are found in a diverse set of organisms. The Minimum Information about a Biosynthetic Gene cluster repository facilitates standardized and centralized storage of experimental data on these gene clusters and their molecular products, by utilizing user-submitted data to translate scientific discoveries into a format that can be analyzed computationally. This accelerates the processes of connecting genes to chemical structures, understanding biosynthetic gene clusters in the context of environmental diversity, and performing computer-assisted design of synthetic gene clusters. Here, we present a Standard Operating Procedure, Excel templates, a tutorial video, and a collection of relevant review literature to support scientists in their efforts to submit data into MiBIG. Further, we provide tools to integrate gene cluster annotation projects into the classroom environment, including workflows and assessment materials.}, } @article {pmid30008469, year = {2018}, author = {Jacob-Dubuisson, F and Mechaly, A and Betton, JM and Antoine, R}, title = {Structural insights into the signalling mechanisms of two-component systems.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {585-593}, doi = {10.1038/s41579-018-0055-7}, pmid = {30008469}, issn = {1740-1534}, abstract = {Two-component systems reprogramme diverse aspects of microbial physiology in response to environmental cues. Canonical systems are composed of a transmembrane sensor histidine kinase and its cognate response regulator. They catalyse three reactions: autophosphorylation of the histidine kinase, transfer of the phosphoryl group to the regulator and dephosphorylation of the phosphoregulator. Elucidating signal transduction between sensor and output domains is highly challenging given the size, flexibility and dynamics of histidine kinases. However, recent structural work has provided snapshots of the catalytic mechanisms of the three enzymatic reactions and described the conformation and dynamics of the enzymatic moiety in the kinase-competent and phosphatase-competent states. Insight into signalling mechanisms across the membrane is also starting to emerge from new crystal structures encompassing both sensor and transducer domains of sensor histidine kinases. In this Progress article, we highlight such important advances towards understanding at the molecular level the signal transduction mechanisms mediated by these fascinating molecular machines.}, } @article {pmid30008468, year = {2018}, author = {Berne, C and Ellison, CK and Ducret, A and Brun, YV}, title = {Bacterial adhesion at the single-cell level.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {616-627}, doi = {10.1038/s41579-018-0057-5}, pmid = {30008468}, issn = {1740-1534}, abstract = {The formation of multicellular microbial communities, called biofilms, starts from the adhesion of a few planktonic cells to the surface. The transition from a free-living planktonic lifestyle to a sessile, attached state is a multifactorial process that is determined by biological, chemical and physical properties of the environment, the surface and the bacterial cell. The initial weak, reversible interactions between a bacterium and a surface strengthen to yield irreversible adhesion. In this Review, we summarize our understanding of the mechanisms governing bacterial adhesion at the single-cell level, including the physical forces experienced by a cell before reaching the surface, the first contact with a surface and the transition from reversible to permanent adhesion.}, } @article {pmid30008036, year = {2018}, author = {Tani-Matsuhana, S and Kusakabe, R and Inoue, K}, title = {Developmental mechanisms of migratory muscle precursors in medaka pectoral fin formation.}, journal = {Development genes and evolution}, volume = {}, number = {}, pages = {}, pmid = {30008036}, issn = {1432-041X}, support = {24-2096//Japan Society for the Promotion of Science/ ; 16K18551//Japan Society for the Promotion of Science/ ; }, abstract = {Limb muscles are formed from migratory muscle precursor cells (MMPs) that delaminate from the ventral region of dermomyotomes and migrate into the limb bud. MMPs remain undifferentiated during migration, commencing differentiation into skeletal muscle after arrival in the limb. However, it is still unclear whether the developmental mechanisms of MMPs are conserved in teleost fishes. Here, we investigate the development of pectoral fin muscles in the teleost medaka Oryzias latipes. Expression of the MMP marker lbx1 is first observed in several somites prior to the appearance of fin buds. lbx1-positive cells subsequently move anteriorly and localize in the prospective fin bud region to differentiate into skeletal muscle cells. To address the developmental mechanisms underlying fin muscle formation, we knocked down tbx5, a gene that is required for fin bud formation. tbx5 morphants showed loss of fin buds, whereas lbx1 expression initiated normally in anterior somites. Unlike in normal embryos, expression of lbx1 was not maintained in migrating fin MMPs or within the fin buds. We suggest that fin MMPs appear to undergo two phases in their development, with an initial specification of MMPs occurring independent of fin buds and a second fin bud-dependent phase of MMP migration and proliferation. Our results showed that medaka fin muscle is composed of MMPs. It is suggested that the developmental mechanism of fin muscle formation is conserved in teleost fishes including medaka. Through this study, we also propose new insights into the developmental mechanisms of MMPs in fin bud formation.}, } @article {pmid30007989, year = {2018}, author = {Mazen, IM and Mekkawy, MK and Ibrahim, HM and Kamel, AK and Hamza, RT and Elaidy, AA}, title = {Clinical and Cytogenetic Study of Egyptian Patients with Sex Chromosome Disorders of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000490840}, pmid = {30007989}, issn = {1661-5433}, abstract = {Disorders of sex development (DSD) are conditions with an abnormal development of chromosomal, gonadal, or anatomical sex. Sex chromosome DSD involve conditions associated with either numerical or structural abnormalities of the sex chromosomes. This study included patients comprising a wide spectrum of presenting features suggestive of DSD and aimed at studying the frequency of sex chromosome abnormalities among 108 Egyptian DSD patients who presented to the Clinical Genetics and Endocrinology Clinics, National Research Centre (NRC) over the 2-year period of 2013 and 2014. The age of the studied patients ranged from 2 months to 39 years. The patients exhibited various presentations, including ambiguous genitalia, undescended testis, hypogonadism, short stature with Turner manifestations, primary or secondary amenorrhea, primary infertility, edema of the dorsum of the hands and feet, and dysmorphic features. The patients were subjected to detailed clinical examination, pubertal staging, and cytogenetic analysis. Our study reported a wide karyotypic diversity and a high frequency of sex chromosome DSD, reaching 44.44% (48/108). In conclusion, we showed a high incidence of sex chromosome DSD among Egyptian DSD patients with wide karyotype/phenotype diversity. The most frequent sex chromosome DSD detected among patients of the present study was Turner syndrome and variants (52.08%; 25/48) followed by Klinefelter syndrome and variants (43.75%; 21/48). Further long term studies are necessary for accurate detection of frequencies of different types of sex chromosomal anomalies and associated phenotypes.}, } @article {pmid30007977, year = {2018}, author = {Lozano, D and González, A and López, JM}, title = {Organization of the Orexin/Hypocretin System in the Brain of Holostean Fishes: Assessment of Possible Relationships with Monoamines and Neuropeptide Y.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {4}, pages = {228-251}, doi = {10.1159/000490172}, pmid = {30007977}, issn = {1421-9743}, abstract = {Holosteans form a small group of actinopterygian fishes considered the sister group of teleosts. Despite this proximity to the biggest group of vertebrates, relatively few studies have been conducted to investigate the organization of the central nervous system of this group of fishes. In this study, the neuroanatomical distribution of orexin/hypocretin-like immunoreactive (OX-ir) cell bodies and fibers was analyzed in the brain of 3 representative species of the 2 orders of extant holosteans, the spotted gar Lepisosteus oculatus, the Florida gar Lepisosteus platyrhincus, and the bowfin Amia calva. Antibodies against orexin-A (OXA) and orexin-B (OXB) were used, which labeled the same cells and fibers throughout the brain. In addition, double immunohistofluorescence was performed for the simultaneous detection of OXA and OXB with tyrosine hydroxylase, serotonin, and neuropeptide Y (NPY), in an attempt to localize the orexinergic structures precisely and study the possible interactions between these neuroactive substances. The pattern of distribution of OX-ir cells in the 3 species was largely similar, showing labeled cells in the preoptic area (POA), and the tuberal and retrotuberal hypothalamic regions, with only subtle differences between species in the density of labeled cells. OX-ir fibers were found in all main brain subdivisions of the 3 species, mostly in the ventral subpallial areas, POA, hypothalamus, posterior tubercle, thalamus, and mesencephalic tectum. Different densities of orexinergic fibers were observed in relation to catecholaminergic and serotoninergic cell groups, as well as an absence of colocalization between orexins and NPY in the same hypothalamic neurons. The comparison of these results with those obtained in other vertebrates highlights a constant pattern of distribution of this system of neurotransmission among different groups of actinopterygian fishes, especially in teleosts. Conserved features shared by all vertebrates studied were also observed, such as the presence of OX-ir cells in the basal hypothalamus, reflecting the preserved functions of these neuropeptides over the course of evolution.}, } @article {pmid30007846, year = {2018}, author = {Scerri, EML and Thomas, MG and Manica, A and Gunz, P and Stock, JT and Stringer, C and Grove, M and Groucutt, HS and Timmermann, A and Rightmire, GP and d'Errico, F and Tryon, CA and Drake, NA and Brooks, AS and Dennell, RW and Durbin, R and Henn, BM and Lee-Thorp, J and deMenocal, P and Petraglia, MD and Thompson, JC and Scally, A and Chikhi, L}, title = {Did Our Species Evolve in Subdivided Populations across Africa, and Why Does It Matter?.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {582-594}, pmid = {30007846}, issn = {1872-8383}, support = {100719/Z/12/Z//Wellcome Trust/United Kingdom ; WT207492//Wellcome Trust/United Kingdom ; WT206194//Wellcome Trust/United Kingdom ; }, abstract = {We challenge the view that our species, Homo sapiens, evolved within a single population and/or region of Africa. The chronology and physical diversity of Pleistocene human fossils suggest that morphologically varied populations pertaining to the H. sapiens clade lived throughout Africa. Similarly, the African archaeological record demonstrates the polycentric origin and persistence of regionally distinct Pleistocene material culture in a variety of paleoecological settings. Genetic studies also indicate that present-day population structure within Africa extends to deep times, paralleling a paleoenvironmental record of shifting and fractured habitable zones. We argue that these fields support an emerging view of a highly structured African prehistory that should be considered in human evolutionary inferences, prompting new interpretations, questions, and interdisciplinary research directions.}, } @article {pmid30007845, year = {2018}, author = {Kindsvater, HK and Dulvy, NK and Horswill, C and Juan-Jordá, MJ and Mangel, M and Matthiopoulos, J}, title = {Overcoming the Data Crisis in Biodiversity Conservation.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {676-688}, doi = {10.1016/j.tree.2018.06.004}, pmid = {30007845}, issn = {1872-8383}, abstract = {How can we track population trends when monitoring data are sparse? Population declines can go undetected, despite ongoing threats. For example, only one of every 200 harvested species are monitored. This gap leads to uncertainty about the seriousness of declines and hampers effective conservation. Collecting more data is important, but we can also make better use of existing information. Prior knowledge of physiology, life history, and community ecology can be used to inform population models. Additionally, in multispecies models, information can be shared among taxa based on phylogenetic, spatial, or temporal proximity. By exploiting generalities across species that share evolutionary or ecological characteristics within Bayesian hierarchical models, we can fill crucial gaps in the assessment of species' status with unparalleled quantitative rigor.}, } @article {pmid30007844, year = {2018}, author = {Darroch, SAF and Smith, EF and Laflamme, M and Erwin, DH}, title = {Ediacaran Extinction and Cambrian Explosion.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {653-663}, doi = {10.1016/j.tree.2018.06.003}, pmid = {30007844}, issn = {1872-8383}, abstract = {The Ediacaran-Cambrian (E-C) transition marks the most important geobiological revolution of the past billion years, including the Earth's first crisis of macroscopic eukaryotic life, and its most spectacular evolutionary diversification. Here, we describe competing models for late Ediacaran extinction, summarize evidence for these models, and outline key questions which will drive research on this interval. We argue that the paleontological data suggest two pulses of extinction - one at the White Sea-Nama transition, which ushers in a recognizably metazoan fauna (the 'Wormworld'), and a second pulse at the E-C boundary itself. We argue that this latest Ediacaran fauna has more in common with the Cambrian than the earlier Ediacaran, and thus may represent the earliest phase of the Cambrian Explosion.}, } @article {pmid30007843, year = {2018}, author = {Bearup, DJ and Childs, DZ and Freckleton, RP}, title = {Funder Restrictions on Application Numbers Lead to Chaos.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {565-568}, doi = {10.1016/j.tree.2018.06.001}, pmid = {30007843}, issn = {1872-8383}, abstract = {Restricting application rates is an attractive way for funders to reduce time and money wasted evaluating uncompetitive applications. However, mathematical models show that this could induce chaotic cycles in total application numbers, increasing uncertainty in the funding process. One emergent property is that smaller institutions spend disproportionally more time unfunded.}, } @article {pmid30007833, year = {2018}, author = {Packer, J and Trapnell, C}, title = {Single-Cell Multi-omics: An Engine for New Quantitative Models of Gene Regulation.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {9}, pages = {653-665}, pmid = {30007833}, issn = {0168-9525}, support = {DP2 HD088158/HD/NICHD NIH HHS/United States ; RC2 DK114777/DK/NIDDK NIH HHS/United States ; }, abstract = {Cells in a multicellular organism fulfill specific functions by enacting cell-type-specific programs of gene regulation. Single-cell RNA sequencing technologies have provided a transformative view of cell-type-specific gene expression, the output of cell-type-specific gene regulatory programs. This review discusses new single-cell genomic technologies that complement single-cell RNA sequencing by providing additional readouts of cellular state beyond the transcriptome. We highlight regression models as a simple yet powerful approach to relate gene expression to other aspects of cellular state, and in doing so, gain insights into the biochemical mechanisms that are necessary to produce a given gene expression output.}, } @article {pmid30007202, year = {2018}, author = {Stegen, JC and Bottos, EM and Jansson, JK}, title = {A unified conceptual framework for prediction and control of microbiomes.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {20-27}, doi = {10.1016/j.mib.2018.06.002}, pmid = {30007202}, issn = {1879-0364}, abstract = {Microbiomes impact nearly all systems on Earth, and despite vast differences among systems, we contend that it is possible and highly beneficial to develop a unified conceptual framework for understanding microbiome dynamics that is applicable across systems. The ability to robustly predict and control environmental and human microbiomes would provide impactful opportunities to sustain and improve the health of ecosystems and humans alike. Doing so requires understanding the processes governing microbiome temporal dynamics, which currently presents an enormous challenge. We contend, however, that new opportunities can emerge by placing studies of both environmental and human microbiome temporal dynamics in the context of a unified conceptual framework. Our conceptual framework poses that factors influencing the temporal dynamics of microbiomes can be grouped into three broad categories: biotic and abiotic history, internal dynamics, and external forcing factors. Both environmental and human microbiome science study these factors, but not in a coordinated or consistent way. Here we discuss opportunities for greater crosstalk across these domains, such as leveraging specific ecological concepts from environmental microbiome science to guide optimization of strategies to manipulate human microbiomes towards improved health. To achieve unified understanding, it is necessary to have a common body of theory developed from explicit iteration between models and molecular-based characterization of microbiome dynamics across systems. Only through such model-experiment iteration will we eventually achieve prediction and control across microbiomes that impact ecosystem sustainability and human health.}, } @article {pmid30007107, year = {2018}, author = {Nguyen, TTX and Moehring, AJ}, title = {A male's seminal fluid increases later competitors' productivity.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1572-1581}, doi = {10.1111/jeb.13352}, pmid = {30007107}, issn = {1420-9101}, support = {//NSERC/ ; }, abstract = {Polyandrous females allow for sexual selection to persist after mating. In the event that females successfully mate with more than one male, sperm competition can occur. Seminal fluid proteins can indirectly affect a male's success in sperm competition through reducing the remating behaviour of females and can directly influence sperm competition through directly displacing competitor sperm or inducing females to eject it. These direct effects on competitor sperm are thought to contribute to the 'second male advantage', whereby the second male to mate sires the majority of offspring. Here, we show an additional mechanism where seminal proteins already present within a mated female appear to enhance offspring production of later competitor males, and contribute to second male advantage. Counter to expectation, increased offspring production was not due to a priming effect of greater early female productivity, nor was it through a general and consistent increase in offspring production. Instead, enhanced productivity was solely through lengthening the time that offspring are sired by the second male, indicating that seminal proteins from the first male to mate may enhance second male advantage through a presumably unintended protective effect on subsequent competitor sperm.}, } @article {pmid30006623, year = {2018}, author = {Scally, A}, title = {High-quality genomes reveal new differences between the great apes.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {336-338}, doi = {10.1038/d41586-018-05679-9}, pmid = {30006623}, issn = {1476-4687}, } @article {pmid30006468, year = {2018}, author = {Sanchez, DA and Dai, Z and Wang, P and Cantu-Chavez, A and Brennan, CJ and Huang, R and Lu, N}, title = {Mechanics of spontaneously formed nanoblisters trapped by transferred 2D crystals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7884-7889}, pmid = {30006468}, issn = {1091-6490}, abstract = {Layered systems of 2D crystals and heterostructures are widely explored for new physics and devices. In many cases, monolayer or few-layer 2D crystals are transferred to a target substrate including other 2D crystals, and nanometer-scale blisters form spontaneously between the 2D crystal and its substrate. Such nanoblisters are often recognized as an indicator of good adhesion, but there is no consensus on the contents inside the blisters. While gas-filled blisters have been modeled and measured by bulge tests, applying such models to spontaneously formed nanoblisters yielded unrealistically low adhesion energy values between the 2D crystal and its substrate. Typically, gas-filled blisters are fully deflated within hours or days. In contrast, we found that the height of the spontaneously formed nanoblisters dropped only by 20-30% after 3 mo, indicating that probably liquid instead of gas is trapped in them. We therefore developed a simple scaling law and a rigorous theoretical model for liquid-filled nanoblisters, which predicts that the interfacial work of adhesion is related to the fourth power of the aspect ratio of the nanoblister and depends on the surface tension of the liquid. Our model was verified by molecular dynamics simulations, and the adhesion energy values obtained for the measured nanoblisters are in good agreement with those reported in the literature. This model can be applied to estimate the pressure inside the nanoblisters and the work of adhesion for a variety of 2D interfaces, which provides important implications for the fabrication and deformability of 2D heterostructures and devices.}, } @article {pmid30006467, year = {2018}, author = {Namba, K and Ogura, S and Ohno, S and Di, W and Kato, K and Wilde, M and Pletikosić, I and Pervan, P and Milun, M and Fukutani, K}, title = {Acceleration of hydrogen absorption by palladium through surface alloying with gold.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7896-7900}, pmid = {30006467}, issn = {1091-6490}, abstract = {Enhancement of hydrogen (H) absorption kinetics improves the performance of hydrogen-purifying membranes and hydrogen-storage materials, which is necessary for utilizing hydrogen as a carbon-free energy carrier. Pd-Au alloys are known to show higher hydrogen solubility than pure Pd. However, the effect of Au on the hydrogen penetration from the surface into the subsurface region has not been clarified so far. Here, we investigate the hydrogen absorption at Pd-Au surface alloys on Pd(110) by means of thermal desorption spectroscopy (TDS) and hydrogen depth profiling with nuclear reaction analysis (NRA). We demonstrate that alloying the Pd(110) surface with submonolayer amounts of Au dramatically accelerates the hydrogen absorption. The degree of acceleration shows a volcano-shaped form against Au coverage. This kinetic enhancement is explained by a reduced penetration barrier mainly caused by a destabilization of chemisorbed surface hydrogen, which is supported by density-functional-theory (DFT) calculations. The destabilization of chemisorbed surface hydrogen is attributed to the change of the surface electronic states as observed by angle-resolved photoemission spectroscopy (ARPES). If generalized, these discoveries may lead to improving and controlling the hydrogen transport across the surfaces of hydrogen-absorbing materials.}, } @article {pmid30006466, year = {2018}, author = {Taylor, GK}, title = {Simple scaling law predicts peak efficiency in oscillatory propulsion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8063-8065}, pmid = {30006466}, issn = {1091-6490}, mesh = {*Efficiency ; *Physical Exertion ; }, } @article {pmid30006465, year = {2018}, author = {Lohnas, LJ and Duncan, K and Doyle, WK and Thesen, T and Devinsky, O and Davachi, L}, title = {Time-resolved neural reinstatement and pattern separation during memory decisions in human hippocampus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7418-E7427}, pmid = {30006465}, issn = {1091-6490}, support = {F32 MH106266/MH/NIMH NIH HHS/United States ; R01 MH074692/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Decision Making ; Electrocorticography ; Female ; Hippocampus/*physiology ; Humans ; Male ; *Memory ; Occipital Lobe/physiology ; Young Adult ; }, abstract = {Mnemonic decision-making has long been hypothesized to rely on hippocampal dynamics that bias memory processing toward the formation of new memories or the retrieval of old ones. Successful memory encoding may be best optimized by pattern separation, whereby two highly similar experiences can be represented by underlying neural populations in an orthogonal manner. By contrast, successful memory retrieval is thought to be supported by a recovery of the same neural pattern laid down during encoding. Here we examined how hippocampal pattern completion and separation emerge over time during memory decisions. We measured electrocorticography activity in the human hippocampus and posterior occipitotemporal cortex (OTC) while participants performed continuous recognition of items that were new, repeated (old), or highly similar to a prior item (similar). During retrieval decisions of old items, both regions exhibited significant reinstatement of multivariate high-frequency activity (HFA) associated with encoding. Further, the extent of reinstatement of encoding patterns during retrieval was correlated with the strength (HFA power) of hippocampal encoding. Evidence for encoding pattern reinstatement was also seen in OTC on trials requiring fine-grained discrimination of similar items. By contrast, hippocampal activity showed evidence for pattern separation during these trials. Together, these results underscore the critical role of the hippocampus in supporting both reinstatement of overlapping information and separation of similar events.}, } @article {pmid30005837, year = {2018}, author = {Raimundo, RLG and Guimarães, PR and Evans, DM}, title = {Adaptive Networks for Restoration Ecology.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {664-675}, doi = {10.1016/j.tree.2018.06.002}, pmid = {30005837}, issn = {1872-8383}, abstract = {The urgent need to restore biodiversity and ecosystem functioning challenges ecology as a predictive science. Restoration ecology would benefit from evolutionary principles embedded within a framework that combines adaptive network models and the phylogenetic structure of ecological interactions. Adaptive network models capture feedbacks between trait evolution, species abundances, and interactions to explain resilience and functional diversity within communities. Phylogenetically-structured network data, increasingly available via next-generation sequencing, inform constraints affecting interaction rewiring. Combined, these approaches can predict eco-evolutionary changes triggered by community manipulation practices, such as translocations and eradications of invasive species. We discuss theoretical and methodological opportunities to bridge network models and data from restoration projects and propose how this can be applied to the functional restoration of ecological interactions.}, } @article {pmid30005715, year = {2018}, author = {Ajayi, AI and Akpan, W}, title = {Determinants of condom use among parous women in North Central and South Western Nigeria: a cross-sectional survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {467}, pmid = {30005715}, issn = {1756-0500}, mesh = {Adult ; *Condoms ; Contraception Behavior/*psychology ; Cross-Sectional Studies ; Female ; Humans ; Nigeria ; Pregnancy ; Safe Sex ; Socioeconomic Factors ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVES: There appears to be an increasing trend of condom use for pregnancy prevention among nulliparous and multiparous women in developing countries. Drawing from a cross-sectional survey involving 1227 women selected using a 3-stage cluster random sampling technique, the study examines the rates of condom use and its determinants among parous women in three states in North Central and South Western Nigeria.

RESULTS: The rate of condom use among parous women was 13.8% and 23.2% among women using any form of contraceptives. After adjusting for confounding factors (religion and marital status, socioeconomic status and access to a health facility in the resident community), women aged 26-35 (AOR 2.7; CI 1.6-4.5), urban residence (AOR: 3.6; CI 2.2-5.8), no income (AOR: 2.7; CI 1.4-4.9), living in Ekiti State (AOR: 1.8; CI 1.2-2.8) and having a tertiary level of education (AOR: 4.5; CI 1.3-15.6) were the independent predictors of condom use. There is an increasing trend of condom use among parous women.}, } @article {pmid30005713, year = {2018}, author = {Tamambang, RF and Njim, T and Njie, AE and Mbuagbaw, L and Mafuta, A and Tchana, M and Choukem, SP}, title = {Adolescent deliveries in urban Cameroon: a retrospective analysis of the prevalence, 6-year trend and adverse outcomes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {469}, pmid = {30005713}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cameroon ; Delivery, Obstetric/adverse effects/*statistics & numerical data ; Female ; Humans ; Infant, Low Birth Weight ; Infant, Newborn ; Pregnancy ; *Pregnancy Outcome ; Pregnancy in Adolescence/*statistics & numerical data ; Premature Birth ; Prevalence ; Retrospective Studies ; }, abstract = {OBJECTIVE: Adolescent deliveries remain a public health problem in most developing countries. The aim of our study was to determine the prevalence, trends and outcome of adolescent deliveries in an urban setting in Cameroon. We carried out a retrospective register analysis over a 6-year period (January 2010-December 2015) at the Saint Albert Le Grand hospital Douala.

RESULTS: The overall prevalence of adolescent deliveries was 8.2% (662 out of 8056). There was a significant decrease over the 6-year period (p-trend: < 0.05). Adolescents were at higher risk of preterm deliveries (gestational age < 37 weeks; odds ratio [OR], 1.7; 95% confidence interval [CI]; 1.3-2.2; p < 0.01): low birth weight (defined as birth weight < 2650 g, OR; 1.7, CI 1.4-2.2, p < 0.01) and asphyxia at 1st minute (OR, 1.5; 95% CI 1.1-2.2; p = 0.02). There was no difference in delivery outcomes between early and late adolescents. Our results suggest that the prevalence of adolescent deliveries is lower in urban settings. Adolescent deliveries are more likely to result in adverse fetal outcomes than adult deliveries. Measures directed towards the prevention of adolescent pregnancies should be implemented to reduce neonatal morbidity and mortality.}, } @article {pmid30005702, year = {2018}, author = {Tada, R and Hidaka, A and Kiyono, H and Kunisawa, J and Aramaki, Y}, title = {Intranasal administration of cationic liposomes enhanced granulocyte-macrophage colony-stimulating factor expression and this expression is dispensable for mucosal adjuvant activity.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {472}, pmid = {30005702}, issn = {1756-0500}, support = {15K18935//Japan Society for the Promotion of Science/ ; 18K06798//Japan Society for the Promotion of Science/ ; 16K08415//Japan Society for the Promotion of Science/ ; 18H02674//Japan Society for the Promotion of Science/ ; 17fk0108223h0002//Japan Agency for Medical Research and Development/ ; 17ek0410032s0102//Japan Agency for Medical Research and Development/ ; 17fk0108207h0002//Japan Agency for Medical Research and Development/ ; 17ak0101068h0001//Japan Agency for Medical Research and Development/ ; 17gm1010006s0101//Japan Agency for Medical Research and Development/ ; }, mesh = {Adjuvants, Immunologic ; Administration, Intranasal ; Animals ; Antibody Formation ; Cations ; Cholesterol/analogs & derivatives ; Fatty Acids, Monounsaturated ; Female ; Granulocyte-Macrophage Colony-Stimulating Factor/*metabolism ; Humans ; Japan ; Liposomes/*administration & dosage/immunology ; Mice ; Nasal Mucosa/immunology/metabolism ; Quaternary Ammonium Compounds ; Rats ; Tokyo ; }, abstract = {OBJECTIVE: Infectious diseases remain a threat to human life. Vaccination against pathogenic microbes is a primary method of treatment as well as prevention of infectious diseases. Particularly mucosal vaccination is a promising approach to fight against most infectious diseases, because mucosal surfaces are a major point of entry for most pathogens. We recently developed an effective mucosal adjuvant of cationic liposomes composed of 1,2-dioleoyl-3-trimethylammonium-propane (DOTAP) and 3β-[N-(N',N'-dimethylaminoethane)-carbamoyl] (DC-chol) (DOTAP/DC-chol liposomes). However, the mechanism(s) underlying the mucosal adjuvant effects exerted by the cationic liposomes have been unclear. In this study, we investigated the role of granulocyte-macrophage colony-stimulating factor (GM-CSF), which was reported to act as a mucosal adjuvant, on the mucosal adjuvant activities of DOTAP/DC-chol liposomes when administered intranasally to mice.

RESULTS: Here, we show that, although intranasal vaccination with cationic liposomes in combination with antigenic protein elicited GM-CSF expression at the site of administration, blocking GM-CSF function by using an anti-GM-CSF neutralizing antibody did not alter antigen-specific antibody production induced by DOTAP/DC-chol liposomes, indicating that GM-CSF may not contribute to the mucosal adjuvant activity of the cationic liposomes when administered intranasally.}, } @article {pmid30005695, year = {2018}, author = {Kpoda, DS and Ajayi, A and Somda, M and Traore, O and Guessennd, N and Ouattara, AS and Sangare, L and Traore, AS and Dosso, M}, title = {Distribution of resistance genes encoding ESBLs in Enterobacteriaceae isolated from biological samples in health centers in Ouagadougou, Burkina Faso.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {471}, pmid = {30005695}, issn = {1756-0500}, mesh = {Burkina Faso ; Child ; Drug Resistance, Bacterial/*genetics ; Enterobacteriaceae/drug effects/*genetics/isolation & purification ; Enterobacteriaceae Infections/*drug therapy ; Escherichia coli ; *Genes, Bacterial ; Humans ; Microbial Sensitivity Tests ; Prospective Studies ; beta-Lactamases/*pharmacology ; }, abstract = {OBJECTIVE: Resistance to antibiotics most especially third generation cephalosporins has assumed a worrisome dimension globally. Genes conferring these resistance which are mediated by enzymes known as extended spectrum beta-lactamases (ESBLs) are now wide spread among several Enterobacteriaceae species. However there is paucity of data regarding the distribution of these genes in Burkina Faso. Hence this prospective study aims to determine the prevalence and distribution of ESBL encoding genes in ESBL producing Enterobacteriaceae strains isolated from clinical samples of patients attending the three major hospitals in Ouagadougou Burkina Faso.

RESULTS: ESBL-encoding genes were assayed in 187 ESBL producing Enterobacteriaceae strains. Among these isolates, the prevalence of ESBL-producing strains with blaTEM, blaSHV and blaCTX-M genes were 26.2% (49/187), 5.9% (11/187) and 40.1% (75/187) respectively. The association of ESBL encoding genes with health centers was statistically significant (p = 0.0209). Approximately 39.6% of E. coli harbored CTX-M and Klebsiella spp. 5.9%. This study demonstrates the dissemination of TEM, SHV and CTX-M genes in ESBL producing Enterobacteriaceae strains in Ouagadougou. Continuous spread of these bacteria poses great public health risk, thus increased surveillance and regulation of antibiotics use is imperative in Burkina Faso.}, } @article {pmid30005694, year = {2018}, author = {Akpakli, DE and Manyeh, AK and Akpakli, JK and Kukula, V and Gyapong, M}, title = {Determinants of access to improved sanitation facilities in rural districts of southern Ghana: evidence from Dodowa Health and Demographic Surveillance Site.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {473}, pmid = {30005694}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Demography ; Female ; Ghana ; Humans ; Male ; Middle Aged ; *Rural Population ; *Sanitation ; *Toilet Facilities ; }, abstract = {OBJECTIVE: Access to improved sanitation facilities is critical to the health and well-being of individuals and communities. However, globally, over 2.5 billion people live without access to safe sanitation facilities and more than 40% of the world population, do not use a toilet, but defecate in the open or in unsanitary places. In Ghana, only 14% of the population have access to improved sanitation facilities with great disparities between rural (8%) and urban (19%) dwellers. This paper sought to examine the determinants of access to improved sanitation facilities by households among rural dwellers in two districts in southern Ghana.

RESULTS: This study, which involved 16,353 household heads from the Dodowa Health and Demographic Surveillance System, found that sanitation facilities used by households were significantly influenced by age, gender, level of education, occupation, marital and socioeconomic status of household heads. It further revealed that a large proportion (85.94%) of the study participants did not have access to improved sanitation facilities. The study therefore recommends that the national sanitation laws must strictly be enforced to ensure each household in Ghana has decent and hygienic toilet facility.}, } @article {pmid30005690, year = {2018}, author = {Benavides-Ward, A and Vasquez-Achaya, F and Silva-Caso, W and Aguilar-Luis, MA and Mazulis, F and Urteaga, N and Del Valle-Mendoza, J}, title = {Helicobacter pylori and its relationship with variations of gut microbiota in asymptomatic children between 6 and 12 years.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {468}, pmid = {30005690}, issn = {1756-0500}, support = {UPC-EXP 01-2018//The study has been supported by Supported by the Incentives for Research of the Universidad Peruana de Ciencias Aplicadas, Lima-Peru/ ; }, mesh = {Anti-Bacterial Agents ; Child ; Cross-Sectional Studies ; Female ; *Gastrointestinal Microbiome ; Growth Disorders ; Helicobacter Infections/diagnosis/*microbiology ; Helicobacter pylori ; Humans ; Male ; Nutrition Assessment ; }, abstract = {OBJECTIVE: To determine the variations in the composition of the intestinal microbiota in asymptomatic children infected with Helicobacter pylori in comparison with children without the infection.

RESULTS: Children infected with H. pylori doubled their probability of presenting 3 of 9 genera of bacteria from the gut microbiota, including: Proteobacteria (p = 0.008), Clostridium (p = 0.040), Firmicutes (p = 0.001) and Prevotella (p = 0.006) in comparison to patients without the infection. We performed a nutritional assessment and found that growth stunting was statistically significantly higher in patients infected with H. pylori (p = 0.046).}, } @article {pmid30005686, year = {2018}, author = {Herek, TA and Robinson, JE and Heavican, TB and Amador, C and Iqbal, J and Cutucache, CE}, title = {Caveolin-1 is dispensable for early lymphoid development, but plays a role in the maintenance of the mature splenic microenvironment.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {470}, pmid = {30005686}, issn = {1756-0500}, mesh = {Animals ; Caveolin 1/*physiology ; Hematologic Neoplasms/*metabolism ; Humans ; Mice ; Neoplasms ; *Signal Transduction ; Splenomegaly/*metabolism ; }, abstract = {OBJECTIVE: Caveolin-1 (CAV1) is known for its role as both a tumor suppressor and an oncogene, harboring a highly context-dependent role within a myriad of malignancies and cell types. In an immunological context, dysregulation of CAV1 expression has been shown to alter immunological signaling functions and suggests a pivotal role for CAV1 in the facilitation of proper immune responses. Nonetheless, it is still unknown how Cav1-deficiency and heterozygosity would impact the development and composition of lymphoid organs in mice. Herein, we investigated the impacts of Cav1-dysregulation on the lymphoid organs in young (12 weeks) and aged (36 weeks) Cav1+/+, Cav1+/-, and Cav1-/- mice.

RESULTS: We observed that only Cav1-deficiency is associated with persistent splenomegaly at all timepoints. Furthermore, no differences in overall body weight were detected (and without sexual dimorphisms). Both aged Cav1+/- and Cav1-/- mice present with decreased CD19+CD22+ B cells and secondary-follicle atrophy, specifically in the spleen, compared with wild-type controls and irrespective of splenomegaly status. Consequently, the demonstrated effects on B cell homeostasis and secondary follicle characteristics prompted our investigation into follicle-derived human B-cell lymphomas. Our investigation points toward CAV1 as a dysregulated protein in follicle-derived B-cell malignancies without harboring a differential expression between more aggressive and indolent hematological malignancies.}, } @article {pmid30005685, year = {2018}, author = {Jayaweera, JAAS and Joseph, A}, title = {Assessment of healthiness among long term inhabiting army soldiers in dry zone of Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {474}, pmid = {30005685}, issn = {1756-0500}, mesh = {Adult ; *Health Status ; Humans ; Incidence ; Male ; Methicillin-Resistant Staphylococcus aureus/isolation & purification ; *Military Personnel ; Noncommunicable Diseases/epidemiology ; Renal Insufficiency, Chronic/epidemiology ; Sri Lanka/epidemiology ; }, abstract = {OBJECTIVES: Military personnel, because of the unique nature of their duties, are reluctant to face stressors. Living in hot and humid conditions they frequently suffer dehydration. Army soldiers living in dry zone of Sri Lanka, were screened for chronic kidney disease (CKD), common non-communicable diseases and methicillin resistant Staphylococcus aureus (MRSA) colonization. Albumin creatinine ratio > 30 mg/g urine taken as cut-off for detection of CKD.

RESULTS: Screened 417 soldiers, all were men and body mass index were 21.4 ± 2.2 kg/m2. They smoke 0.5 ± 0.1 pack years while consume alcohol 32 ± 3 units/week and were having 100/min average daily moderate physical activity. Eight of them (0.2%) were having essential hypertension, 4 (0.1%) of them were having diabetes mellitus. Blood cholesterol was within normal range. CKD unknown etiology (CKDu) prevalence among screened army soldiers was 0.009. All were from native army recruits. Further, 71.2% had MRSA colonization. In a group of middle aged army recruits, despite tobacco smoking and moderate level of alcohol consumption while continuously having healthy dietary practices with physical activities would leads to low prevalence of communicable diseases. Further, compared to native group of solders, visitors but living long time recruits CKDu incidence is zero.}, } @article {pmid30005656, year = {2018}, author = {Liao, W and Li, S and Lu, C and Peng, M}, title = {Tau GSTs involved in regulation of leaf abscission by comparison the gene profiling of MeGSTs in various abscission-promoting treatments in cassava abscission zones.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {45}, pmid = {30005656}, issn = {1471-2156}, support = {31471551//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Glutathione S-transferases (GSTs) have been reported to regulate the plant tolerance to environmental stresses. Many plant GSTs exhibited the roles on promoting tolerance to drought stress, oxidative stress and plant hormones. The biological function of GSTs has been well characterized in Arabidopsis thaliana in response to exogenous environmental stresses. However, their regulation function under exogenous environmental stresses regulating leaf abscission in cassava (Manihot esculenta Crantz) remained unknown.

RESULTS: Here, 83 GSTs were identified from tropical plant cassava. The amino acid motifs and phylogenetic analyses indicated that MeGSTs were divided into 9 classes. The global expression analyses were carried out to analyze the gene expression patterns of MeGST in cassava abscission zones by comparing the MeGST genes expression patterns in both ethylene and drought induced cassava leaf abscission. Totally, 34 GSTs were detected to express in both ethylene and drought induced leaf abscission in cassava abscission zones. Comparison of GST expression profiling between ethylene and drought induced leaf abscission suggested that Tau GST genes showed with the similar expression in both treatments induced leaf abscission in cassava abscission zone. GO annotation indicated that all 17 Tau GST genes participated in the pathway of toxin catabolism (GO: 0009407). The expression levels of 17 Tau MeGST genes were analyzed in two cassava cultivars, 'SC124' and 'Arg7', the two cultivars exhibit different levels of leaf abscission when suffered from the same environmental stress. Higher expression levels of Tau MeGSTs were detected in the precocious abscission Arg7 cultivar, while lower expression levels in delayed abscission SC124 cultivar. All the results indicated that Tau MeGSTs have the function in regulation the cassava leaf abscission under environmental stresses.

CONCLUSION: Analysis of the expression patterns of GSTs in various abscission-promoting treatments in cassava abscission zones helps us to understand the possible roles of GSTs in cassava leaf abscission.}, } @article {pmid30005645, year = {2018}, author = {Hokan, M and Zimmermann, E and Radespiel, U and Andriatsitohaina, B and Rasoloharijaona, S and Strube, C}, title = {Are sleeping site ecology and season linked to intestinal helminth prevalence and diversity in two sympatric, nocturnal and arboreal primate hosts (Lepilemur edwardsi and Avahi occidentalis)?.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {22}, pmid = {30005645}, issn = {1472-6785}, abstract = {BACKGROUND: Various factors, such as climate, body size and sociality are often linked to parasitism. This constrains the identification of other determinants driving parasite infections. Here, we investigate for the first time intestinal parasites in two sympatric arboreal primate species, which share similar activity patterns, feeding ecology, body size and sociality, and cope with the same climate conditions, but differ in sleeping site ecology: the Milne-Edward's sportive lemur (Lepilemur edwardsi) and the Western woolly lemur (Avahi occidentalis). Comparison of these two species aimed to test whether differences in sleeping sites are related to differences in parasite infection patterns. Additionally, gender and seasonal factors were taken into account. Animals were radio-collared to record their sleeping site dynamics and to collect fecal samples to assess intestinal parasitism during both the dry and the rainy season.

RESULTS: Only low parasite diversity was detected, which is attributable to the strict arboreal lifestyle of these lemurs, limiting their contact with infective parasite stages. L. edwardsi, which sleeps in tree holes and repeatedly uses the same sleeping site, excreted eggs of strongyle and oxyurid nematodes, whereby strongyles always occurred in coinfection with oxyurids. In contrast, A. occidentalis, which sleeps on open branches and frequently changes sleeping sites, only excreted eggs of strongyle nematodes. This difference can be attributed to a potential favorable environment presented by tree holes for infective stages, facilitating parasitic transmission. Additionally, Strongylida in A. occidentalis were only observed in the rainy season, suggesting an arrested development during the dry season in the nematodes' life cycle. Males and females of both lemur species showed the same frequency of parasitism. No differences in body mass of infected and non-infected individuals were observed, indicating that the animals' body condition remains unaffected by the detected gastrointestinal parasites.

CONCLUSIONS: The comparison of two primate hosts with a very similar lifestyle suggests an influence of the sleeping site ecology on intestinal parasites. In A. occidentalis there was a clear seasonal difference in strongyle egg excretion. These results improve our understanding of the parasite ecology in these endangered primate species, which may be critical in the light of species conservation.}, } @article {pmid30005633, year = {2018}, author = {Xue, Z and Warren, RL and Gibb, EA and MacMillan, D and Wong, J and Chiu, R and Hammond, SA and Yang, C and Nip, KM and Ennis, CA and Hahn, A and Reynolds, S and Birol, I}, title = {Recurrent tumor-specific regulation of alternative polyadenylation of cancer-related genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {536}, pmid = {30005633}, issn = {1471-2164}, support = {HHSN261201400007C/CA/NCI NIH HHS/United States ; R21 CA187910/CA/NCI NIH HHS/United States ; R21CA187910//National Human Genome Research Institute/ ; }, mesh = {3' Untranslated Regions ; Cloud Computing ; Databases, Genetic ; Fibroblast Growth Factor 2/genetics ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasm Recurrence, Local/genetics ; Neoplasms/*genetics/pathology ; Polyadenylation ; RNA Cleavage ; RNA, Messenger/*genetics/metabolism ; Software ; }, abstract = {BACKGROUND: Alternative polyadenylation (APA) results in messenger RNA molecules with different 3' untranslated regions (3' UTRs), affecting the molecules' stability, localization, and translation. APA is pervasive and implicated in cancer. Earlier reports on APA focused on 3' UTR length modifications and commonly characterized APA events as 3' UTR shortening or lengthening. However, such characterization oversimplifies the processing of 3' ends of transcripts and fails to adequately describe the various scenarios we observe.

RESULTS: We built a cloud-based targeted de novo transcript assembly and analysis pipeline that incorporates our previously developed cleavage site prediction tool, KLEAT. We applied this pipeline to elucidate the APA profiles of 114 genes in 9939 tumor and 729 tissue normal samples from The Cancer Genome Atlas (TCGA). The full set of 10,668 RNA-Seq samples from 33 cancer types has not been utilized by previous APA studies. By comparing the frequencies of predicted cleavage sites between normal and tumor sample groups, we identified 77 events (i.e. gene-cancer type pairs) of tumor-specific APA regulation in 13 cancer types; for 15 genes, such regulation is recurrent across multiple cancers. Our results also support a previous report showing the 3' UTR shortening of FGF2 in multiple cancers. However, over half of the events we identified display complex changes to 3' UTR length that resist simple classification like shortening or lengthening.

CONCLUSIONS: Recurrent tumor-specific regulation of APA is widespread in cancer. However, the regulation pattern that we observed in TCGA RNA-seq data cannot be described as straightforward 3' UTR shortening or lengthening. Continued investigation into this complex, nuanced regulatory landscape will provide further insight into its role in tumor formation and development.}, } @article {pmid30005624, year = {2018}, author = {Severing, E and Faino, L and Jamge, S and Busscher, M and Kuijer-Zhang, Y and Bellinazzo, F and Busscher-Lange, J and Fernández, V and Angenent, GC and Immink, RGH and Pajoro, A}, title = {Arabidopsis thaliana ambient temperature responsive lncRNAs.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {145}, pmid = {30005624}, issn = {1471-2229}, support = {849.13.005 for the project ERACAPS13.012, FLOWPLAST//NWO/ ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) have emerged as new class of regulatory molecules in animals where they regulate gene expression at transcriptional and post-transcriptional level. Recent studies also identified lncRNAs in plant genomes, revealing a new level of transcriptional complexity in plants. Thousands of lncRNAs have been predicted in the Arabidopsis thaliana genome, but only a few have been studied in depth.

RESULTS: Here we report the identification of Arabidopsis lncRNAs that are expressed during the vegetative stage of development in either the shoot apical meristem or in leaves. We found that hundreds of lncRNAs are expressed in these tissues, of which 50 show differential expression upon an increase in ambient temperature. One of these lncRNAs, FLINC, is down-regulated at higher ambient temperature and affects ambient temperature-mediated flowering in Arabidopsis.

CONCLUSION: A number of ambient temperature responsive lncRNAs were identified with potential roles in the regulation of temperature-dependent developmental changes, such as the transition from the vegetative to the reproductive (flowering) phase. The challenge for the future is to characterize the biological function and molecular mode of action of the large number of ambient temperature-regulated lncRNAs that have been identified in this study.}, } @article {pmid30005621, year = {2018}, author = {Rodrussamee, N and Sattayawat, P and Yamada, M}, title = {Highly efficient conversion of xylose to ethanol without glucose repression by newly isolated thermotolerant Spathaspora passalidarum CMUWF1-2.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {73}, pmid = {30005621}, issn = {1471-2180}, abstract = {BACKGROUND: Efficient bioconversion of lignocellulosic biomass to bioethanol is one of key challenges in the situation of increasing bioethanol demand. The ethanologenic microbes for such conversion are required to possess abilities of utilization of various sugars including xylose and arabinose in lignocellulosic biomass. As required additional characteristics, there are a weak or no glucose repression that allows cells to simultaneously utilize various sugars together with glucose and thermotolerance for fermentation at high temperatures, which has several advantages including reduction of cooling cost. Spathaspora passalidarum ATCC MYA-4345, a type strains, isolated previously have mainly of these abilities or characteristics but its thermotolerance is not so strong and its glucose repression on xylose utilization is revealed.

RESULTS: Newly isolated S. passalidarum CMUWF1-2 was found to have a high ability to produce ethanol from various sugars included in lignocellulosic biomass at high temperatures. The strain achieved ethanol yields of 0.43 g, 0.40 g and 0.20 g ethanol/g xylose at 30 °C, 37 °C and 40 °C, respectively. Interestingly, no significant glucose repression was observed in experiments with mixed sugars, being consistent with the strong resistance to 2-deoxyglucose, and antimycin A showed no effect on its growth in xylose medium. Moreover, the strain was tolerant to glucose and ethanol at concentrations up to 35.0% (w/v) and 8.0% (v/v), respectively.

CONCLUSIONS: S. passalidarum CMUWF1-2 was shown to achieve efficient production of ethanol from various sugars and a high ethanol yield from xylose with little accumulation of xylitol. The strain also exhibited stress-resistance including thermotolerance and no detectable glucose repression as beneficial characteristics. Therefore, S. passalidarum CMUWF1-2 has remarkable potential for conversion of lignocellulosic biomass to bioethanol.}, } @article {pmid30005620, year = {2018}, author = {Stedman, A and Maluquer de Motes, C and Lesellier, S and Dalley, D and Chambers, M and Gutierrez-Merino, J}, title = {Lactic acid Bacteria isolated from European badgers (Meles meles) reduce the viability and survival of Bacillus Calmette-Guerin (BCG) vaccine and influence the immune response to BCG in a human macrophage model.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {74}, pmid = {30005620}, issn = {1471-2180}, abstract = {BACKGROUND: Bovine tuberculosis (bTB) caused by Mycobacterium bovis is the most serious endemic disease affecting livestock in the UK. The European badger (Meles meles) is the most important wildlife reservoir of bTB transmission to cattle, making eradication particularly difficult. In this respect, oral vaccination with the attenuated M. bovis vaccine Bacillus Calmette-Guerin (BCG) has been suggested as a wide-scale intervention to reduce bTB infection in badgers. However, experimental studies show variable protection. Among the possibilities for this variation is that the resident gut bacteria may influence the success of oral vaccination in badgers; either through competitive exclusion and/or inhibition, or via effects on the host immune system. In order to explore this possibility, we have tested whether typical gut commensals such as Lactic Acid Bacteria (LAB) have the capacity to impact on the viability and survival rate of BCG and to modulate the immune response to BCG using an in vitro model.

RESULTS: Twelve LAB isolated from badger faeces displayed inhibitory activity to BCG that was species-dependent. Weissella had a bacteriostatic effect, whereas isolates of enterococci, lactobacilli and pediococci had a more bactericidal activity. Furthermore, BCG-induced activation of the pro-inflammatory transcription factor NF-κB in human THP-1 macrophages was modulated by LAB in a strain-dependent manner. Most pediococci enhanced NF-κB activation but one strain had the opposite effect. Interestingly, isolates of enterococci, lactobacilli and weissella had different effects as immunomodulators of BCG-induced macrophage responses as some had no significant influence on NF-κB activation, but others increased it significantly.

CONCLUSIONS: Our in vitro results show that LAB isolated from badgers exhibit significant inhibitory activity against BCG and influence the immune activation mediated by BCG in a human macrophage assay. These findings suggest that gut commensal bacteria could play a role in influencing the outcome of oral BCG vaccination. Inactivated cells of LAB, or LAB that are bacteriostatic but have a synergistic immunostimulatory effect with BCG, could be potential adjuvants to be used for oral vaccination in badgers. Further work is needed to take into account the complex nature of the gut microbiome, specific immunity of the badger and the in vivo context.}, } @article {pmid30005607, year = {2018}, author = {Lee, H and Nguyen, MP and Choi, Y and Kim, YH}, title = {Minimum InDel pattern analysis of the Zika virus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {535}, pmid = {30005607}, issn = {1471-2164}, support = {2016R1A2B2014493//National Research Foundation of Korea/ ; }, mesh = {Amino Acid Sequence ; Dengue/pathology/virology ; Dengue Virus/genetics/isolation & purification ; Evolution, Molecular ; Gene Frequency ; *Genome, Viral ; Humans ; INDEL Mutation ; Polyproteins/genetics ; Sequence Alignment ; Viral Proteins/genetics ; Zika Virus/*genetics/isolation & purification ; Zika Virus Infection/pathology/virology ; }, abstract = {BACKGROUND: The Zika virus (ZIKV) can cause microcephaly and congenital abnormalities in the foetus. Recent studies have provided insights into the evolution of ZIKV from the current and previous outbreaks, but the types have not been determined.

RESULTS: We analysed the insertions and deletions (InDels) in 212 ZIKV polyproteins and 5 Dengue virus (DENV) reference sequences. Spearman correlation tests for the minimum InDel (minInDel) patterns were used to assess the type of polyprotein. Using the minInDel frequencies calculated from polyproteins with 11 elements, likelihood estimation was conducted to correct the evolutionary distance. The minInDel-corrected tree topology clearly distinguished between the ZIKV types (I and II) with a unique minInDel character in the E protein. From the 10-year average genetic distance, the African and Asian lineages of ZIKV-II were estimated to have occurred ~ 270 years ago, which is unlikely for ZIKV-I.

CONCLUSIONS: The minInDel pattern analysis showed that the minInDel in the E protein is targetable for the rapid detection and determination of the virus types.}, } @article {pmid30005606, year = {2018}, author = {Safari, I and Goymann, W}, title = {Certainty of paternity in two coucal species with divergent sex roles: the devil takes the hindmost.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {110}, pmid = {30005606}, issn = {1471-2148}, support = {Go985/2//DFG/International ; GEFNE92-13//National Geographic Society/International ; }, mesh = {Animals ; Birds/*physiology ; Clutch Size ; Female ; Male ; Phylogeny ; Probability ; Sex Ratio ; Sexual Behavior, Animal/*physiology ; Species Specificity ; Survival Analysis ; }, abstract = {BACKGROUND: Certainty of paternity is considered an important factor in the evolution of paternal care. Several meta-analyses across birds support this idea, particularly for species with altricial young. However, the role of certainty of paternity in the evolution and maintenance of exclusive paternal care in the black coucal (Centropus grillii), which is the only known altricial bird species with male-only care, is not well understood. Here we investigated whether the differences in levels of paternal care in the black coucal and its sympatric congener, the bi-parental white-browed coucal (Centropus superciliosus), are shaped by extra-pair paternity.

RESULTS: We found that male black coucals experienced a substantially higher loss of paternity than white-browed coucals. Further, unlike any previously reported bird species, extra-pair offspring in black coucals represented mainly the last hatchlings of the broods, and these last hatchlings were more likely to disappear during partial-brood loss.

CONCLUSION: The results suggest that exclusive paternal care in black coucals is not maintained by male certainty of parentage, and extra-pair fertilizations are unlikely to be a female strategy for seeking 'good genes'. Extra-pair paternity in black coucals may reflect the inability of males to guard and copulate with the female after the onset of incubation, and a female strategy to demonstrate her commitment to other males of her social group.}, } @article {pmid30005605, year = {2018}, author = {Escobar, N and Valdes, ID and Keizer, EM and Ordonez, SR and Ohm, RA and Wösten, HAB and de Cock, H}, title = {Expression profile analysis reveals that Aspergillus fumigatus but not Aspergillus niger makes type II epithelial lung cells less immunological alert.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {534}, pmid = {30005605}, issn = {1471-2164}, mesh = {A549 Cells ; Aspergillus fumigatus/*pathogenicity ; Aspergillus niger/*pathogenicity ; Down-Regulation ; Epithelial Cells/cytology/metabolism/microbiology ; Gene Expression Profiling ; Host-Pathogen Interactions/genetics ; Humans ; Interleukin-8/genetics/metabolism ; RNA/chemistry/isolation & purification/metabolism ; Sequence Analysis, RNA ; Up-Regulation ; }, abstract = {BACKGROUND: Aspergillus fumigatus is the main causative agent of aspergillosis. Infections rarely occur in immunocompetent individuals, indicating efficient clearance of conidia by pulmonary defense mechanisms. Other aspergilli like Aspergillus niger also cause infections but to a much lesser extent. Our previous studies showed that A. fumigatus and A. niger have different behavior in the presence of type II alveolar A549 epithelial cells. A. fumigatus conidia are more efficiently internalized by these cells and germination is delayed when compared to A. niger. In addition, hyphae that have escaped the epithelial cells grow parallel to the epithelium, while A. niger grows away from this cell layer.

RESULTS: Here it is shown that global gene expression of A. fumigatus and A. niger is markedly different upon contact with A549 cells. A total of 545 and 473 genes of A. fumigatus and A. niger, respectively, were differentially expressed when compared to growth in the absence of A549 cells. Notably, only 53 genes (approximately 10%) were shared in these gene sets. The different response was also illustrated by the fact that only 4 out of 75 GO terms were shared that were enriched in the differentially expressed gene sets. The orthologues of A. fumigatus genes involved in hypoxia regulation and heat shock were also up-regulated in A. niger, whereas thioredoxin reductase and allergen genes were found up-regulated in A. fumigatus but down-regulated in A. niger. Infection with A. fumigatus resulted in only 62 up and 47 down-regulated genes in A549. These numbers were 17 and 34 in the case of A. niger. GO terms related with immune response were down-regulated upon exposure to A. fumigatus but not in the case of A. niger. This indicates that A. fumigatus reprograms A549 to be less immunologically alert.

CONCLUSIONS: Our dual transcriptomic analysis supports earlier observations of a marked difference in life style between A. fumigatus and A. niger when grown in the presence of type II epithelial cells. The results indicate important differences in gene expression, amongst others down regulation of immune response genes in lung epithelial cells by A. fumigatus but not by A niger.}, } @article {pmid30005604, year = {2018}, author = {Moulos, P and Alexandratos, A and Nellas, I and Dedos, SG}, title = {Refining a steroidogenic model: an analysis of RNA-seq datasets from insect prothoracic glands.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {537}, pmid = {30005604}, issn = {1471-2164}, support = {Kapodistrias:11240//National and Kapodistrian University of Athens/ ; Greece-Siemens program//State Scholarships Foundation/ ; }, mesh = {Animals ; Bombyx/*genetics ; Cholesterol/metabolism ; Cyclic AMP/metabolism ; Drosophila melanogaster/*genetics ; Endocrine Glands/*metabolism ; Insect Proteins/genetics/metabolism ; *Models, Biological ; RNA/chemistry/isolation & purification/metabolism ; Sequence Analysis, RNA ; Signal Transduction/genetics ; Transcriptome ; }, abstract = {BACKGROUND: The prothoracic gland (PG), the principal steroidogenic organ of insects, has been proposed as a model for steroid hormone biosynthesis and regulation.

RESULTS: To validate the robustness of the model, we present an analysis of accumulated transcriptomic data from PGs of two model species, Drosophila melanogaster and Bombyx mori. We identify that the common core components of the model in both species are encoded by nine genes. Five of these are Halloween genes whose expression differs substantially between the PGs of these species.

CONCLUSIONS: We conclude that the PGs can be a model for steroid hormone synthesis and regulation within the context of mitochondrial cholesterol transport and steroid biosynthesis but beyond these core mechanisms, gene expression in insect PGs is too diverse to fit in a context-specific model and should be analysed within a species-specific framework.}, } @article {pmid30005603, year = {2018}, author = {Shin, SY and Jeong, JS and Lim, JY and Kim, T and Park, JH and Kim, JK and Shin, C}, title = {Transcriptomic analyses of rice (Oryza sativa) genes and non-coding RNAs under nitrogen starvation using multiple omics technologies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {532}, pmid = {30005603}, issn = {1471-2164}, support = {Next-Generation BioGreen 21 Program (No. PJ01332501)//Rural Development Administration/ ; }, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Plant ; MicroRNAs/genetics/metabolism ; Nitrogen/*deficiency ; Oryza/*genetics/metabolism ; Phosphates/metabolism ; Plant Roots/genetics/metabolism ; Plant Shoots/genetics/metabolism ; RNA, Long Noncoding/genetics/metabolism ; RNA, Untranslated/*genetics/metabolism ; Sequence Analysis, RNA ; Stress, Physiological ; *Transcriptome ; }, abstract = {BACKGROUND: Nitrogen (N) is a key macronutrient essential for plant growth, and its availability has a strong influence on crop development. The application of synthetic N fertilizers on crops has increased substantially in recent decades; however, the applied N is not fully utilized due to the low N use efficiency of crops. To overcome this limitation, it is important to understand the genome-wide responses and functions of key genes and potential regulatory factors in N metabolism.

RESULTS: Here, we characterized changes in the rice (Oryza sativa) transcriptome, including genes, newly identified putative long non-coding RNAs (lncRNAs), and microRNAs (miRNAs) and their target mRNAs in response to N starvation using four different transcriptome approaches. Analysis of rice genes involved in N metabolism and/or transport using strand-specific RNA-Seq identified 2588 novel putative lncRNA encoding loci. Analysis of previously published RNA-Seq datasets revealed a group of N starvation-responsive lncRNAs showing differential expression under other abiotic stress conditions. Poly A-primed sequencing (2P-Seq) revealed alternatively polyadenylated isoforms of N starvation-responsive lncRNAs and provided precise 3' end information on the transcript models of these lncRNAs. Analysis of small RNA-Seq data identified N starvation-responsive miRNAs and down-regulation of miR169 family members, causing de-repression of NF-YA, as confirmed by strand-specific RNA-Seq and qRT-PCR. Moreover, we profiled the N starvation-responsive down-regulation of root-specific miRNA, osa-miR444a.4-3p, and Degradome sequencing confirmed MADS25 as a novel target gene.

CONCLUSIONS: In this study, we used a combination of multiple RNA-Seq analyses to extensively profile the expression of genes, newly identified lncRNAs, and microRNAs in N-starved rice roots and shoots. Data generated in this study provide an in-depth understanding of the regulatory pathways modulated by N starvation-responsive miRNAs. The results of comprehensive, large-scale data analysis provide valuable information on multiple aspects of the rice transcriptome, which may be useful in understanding the responses of rice plants to changes in the N supply status of soil.}, } @article {pmid30005602, year = {2018}, author = {Caniglia, R and Fabbri, E and Hulva, P and Bolfíková, BČ and Jindřichová, M and Stronen, AV and Dykyy, I and Camatta, A and Carnier, P and Randi, E and Galaverni, M}, title = {Wolf outside, dog inside? The genomic make-up of the Czechoslovakian Wolfdog.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {533}, pmid = {30005602}, issn = {1471-2164}, support = {1337-00007//Danish Natural Science Research Council/ ; 20175018//IGA CULS/ ; 20175006//CIGA/ ; 20175018//IGA CULS/ ; }, mesh = {Animals ; Bayes Theorem ; Catechol O-Methyltransferase/genetics ; Circadian Rhythm/genetics ; Czechoslovakia ; DNA/isolation & purification/metabolism ; Dogs/*genetics ; Gene Ontology ; Genetics, Population ; *Genome ; Hybridization, Genetic ; Linkage Disequilibrium ; Lipid Metabolism/genetics ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Wolves/*genetics ; }, abstract = {BACKGROUND: Genomic methods can provide extraordinary tools to explore the genetic background of wild species and domestic breeds, optimize breeding practices, monitor and limit the spread of recessive diseases, and discourage illegal crossings. In this study we analysed a panel of 170k Single Nucleotide Polymorphisms with a combination of multivariate, Bayesian and outlier gene approaches to examine the genome-wide diversity and inbreeding levels in a recent wolf x dog cross-breed, the Czechoslovakian Wolfdog, which is becoming increasingly popular across Europe.

RESULTS: Pairwise FST values, multivariate and assignment procedures indicated that the Czechoslovakian Wolfdog was significantly differentiated from all the other analysed breeds and also well-distinguished from both parental populations (Carpathian wolves and German Shepherds). Coherently with the low number of founders involved in the breed selection, the individual inbreeding levels calculated from homozygosity regions were relatively high and comparable with those derived from the pedigree data. In contrast, the coefficient of relatedness between individuals estimated from the pedigrees often underestimated the identity-by-descent scores determined using genetic profiles. The timing of the admixture and the effective population size trends estimated from the LD patterns reflected the documented history of the breed. Ancestry reconstruction methods identified more than 300 genes with excess of wolf ancestry compared to random expectations, mainly related to key morphological features, and more than 2000 genes with excess of dog ancestry, playing important roles in lipid metabolism, in the regulation of circadian rhythms, in learning and memory processes, and in sociability, such as the COMT gene, which has been described as a candidate gene for the latter trait in dogs.

CONCLUSIONS: In this study we successfully applied genome-wide procedures to reconstruct the history of the Czechoslovakian Wolfdog, assess individual wolf ancestry proportions and, thanks to the availability of a well-annotated reference genome, identify possible candidate genes for wolf-like and dog-like phenotypic traits typical of this breed, including commonly inherited disorders. Moreover, through the identification of ancestry-informative markers, these genomic approaches could provide tools for forensic applications to unmask illegal crossings with wolves and uncontrolled trades of recent and undeclared wolfdog hybrids.}, } @article {pmid30005592, year = {2018}, author = {Qu, J and Zhou, Y and Yu, J and Zhang, J and Han, Y and Zou, X}, title = {Estimated divergence times of Hirsutella (asexual morphs) in Ophiocordyceps provides insight into evolution of phialide structure.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {111}, pmid = {30005592}, issn = {1471-2148}, support = {31360031//National Natural Science Foundation of China/International ; }, mesh = {Animals ; *Biological Evolution ; Fossils ; Hypocreales/classification/*physiology ; Phylogeny ; Species Specificity ; Time Factors ; }, abstract = {BACKGROUND: Hirsutella Pat genus, the asexual morphs of the Ophiocordyceps Sung, is globally distributed entomopathogenic fungi, which infect a variety of arthropods, mites and nematodes. The fungal species also have shown potential application in the field of biological control, bio-medicine and food development. Although these fungi are synonymized under Ophiocordyceps, formal taxonomic assignments remain necessary for classification of species in Hirsutella. However, due to the heterogeneity and complexity of Hirsutella genus, more detailed taxonomic and phylogenetic analyses are required to address the following subjects: (1) the relationships between the phialide morphological characteristics and phylogenetic information of Hirsutella with asexual morphs, (2) the origin and evolution of the phialide structure, and (3) host specificity and fungal pathogenicity.

RESULTS: Five typical phialide structures are summarized, in which the variation in phialide characteristics overlaps well with phylogenetic information. A new member of the special twisted neck clade in the Hirsutella-like group, Ophiocordyceps retorta, was reported based on these analyses. The molecular clock calibration analysis based on one fossil record revealed that Hirsutella (asexual morph) species originated from a common ancestor approximately 102 million years ago (Mya) (Early Cretaceous, Lower Albian) and then resolved into two major lineages. One lineage was typically phialidic, which was a larger shape, including H. guyana, H. nodulosa and H. sinensis clades (86.9 Mya, 95% highest posterior density (HPD): 69.1-101.4 Mya). Another main lineage of the phialides was more diversified and smaller than the former, which included H. citriformis and H. thompsonii clades (71.9 Mya, 95% HPD: 41.8-99.6 Mya).

CONCLUSIONS: Our results showed that certain phialide characteristics of Hirsutella were phylogenetically informative for two groups of taxa. The differentiation of the phialides structures in the major clades demonstrated a clear evolutionary path of Hirsutella (asexual morph) species, which exhibited two trends depending on the host size. Fungi in one of the groups displayed elongated conidiogenous cells with increased complexity of auxiliary structures from the mycelia. The species in another group reduced the volume of phialides and spores, which might be due to an energy-efficient strategy. These results suggested that a common origin allowed for diversification of given clades into separate niches. The distinct parallel evolutionary path combined with the specific phialides structure might result in the host specificity of Hirsutella (asexual morphs). A direct relationship between Hirsutella (asexual morphs) and the Cretaceous-Tertiary extinction was not found, which suggested that the diversity of phialides is more likely to be caused by long-term environmental adaptation and evolution rather than dramatic extinction events. This evolutionary result might correspond to the background of important biological and geological events in the late Cretaceous occurring near the divergence times of Hirsutella (asexual morphs).}, } @article {pmid30005591, year = {2018}, author = {Eguchi, R and Karim, MB and Hu, P and Sato, T and Ono, N and Kanaya, S and Altaf-Ul-Amin, M}, title = {An integrative network-based approach to identify novel disease genes and pathways: a case study in the context of inflammatory bowel disease.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {264}, pmid = {30005591}, issn = {1471-2105}, abstract = {BACKGROUND: There are different and complicated associations between genes and diseases. Finding the causal associations between genes and specific diseases is still challenging. In this work we present a method to predict novel associations of genes and pathways with inflammatory bowel disease (IBD) by integrating information of differential gene expression, protein-protein interaction and known disease genes related to IBD.

RESULTS: We downloaded IBD gene expression data from NCBI's Gene Expression Omnibus, performed statistical analysis to determine differentially expressed genes, collected known IBD genes from DisGeNet database, which were used to construct a IBD related PPI network with HIPPIE database. We adapted our graph-based clustering algorithm DPClusO to cluster the disease PPI network. We evaluated the statistical significance of the identified clusters in the context of determining the richness of IBD genes using Fisher's exact test and predicted novel genes related to IBD. We showed 93.8% of our predictions are correct in the context of other databases and published literatures related to IBD.

CONCLUSIONS: Finding disease-causing genes is necessary for developing drugs with synergistic effect targeting many genes simultaneously. Here we present an approach to identify novel disease genes and pathways and discuss our approach in the context of IBD. The approach can be generalized to find disease-associated genes for other diseases.}, } @article {pmid30005590, year = {2018}, author = {Xiao, C and Li, W and Deng, H and Chen, X and Yang, Y and Xie, Q and Han, H}, title = {Effective automated pipeline for 3D reconstruction of synapses based on deep learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {263}, pmid = {30005590}, issn = {1471-2105}, abstract = {BACKGROUND: The locations and shapes of synapses are important in reconstructing connectomes and analyzing synaptic plasticity. However, current synapse detection and segmentation methods are still not adequate for accurately acquiring the synaptic connectivity, and they cannot effectively alleviate the burden of synapse validation.

RESULTS: We propose a fully automated method that relies on deep learning to realize the 3D reconstruction of synapses in electron microscopy (EM) images. The proposed method consists of three main parts: (1) training and employing the faster region convolutional neural networks (R-CNN) algorithm to detect synapses, (2) using the z-continuity of synapses to reduce false positives, and (3) combining the Dijkstra algorithm with the GrabCut algorithm to obtain the segmentation of synaptic clefts. Experimental results were validated by manual tracking, and the effectiveness of our proposed method was demonstrated. The experimental results in anisotropic and isotropic EM volumes demonstrate the effectiveness of our algorithm, and the average precision of our detection (92.8% in anisotropy, 93.5% in isotropy) and segmentation (88.6% in anisotropy, 93.0% in isotropy) suggests that our method achieves state-of-the-art results.

CONCLUSIONS: Our fully automated approach contributes to the development of neuroscience, providing neurologists with a rapid approach for obtaining rich synaptic statistics.}, } @article {pmid30004822, year = {2018}, author = {Rapisarda, C and Tassinari, M and Gubellini, F and Fronzes, R}, title = {Using Cryo-EM to Investigate Bacterial Secretion Systems.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {231-254}, doi = {10.1146/annurev-micro-090817-062702}, pmid = {30004822}, issn = {1545-3251}, abstract = {Bacterial secretion systems are responsible for releasing macromolecules to the extracellular milieu or directly into other cells. These membrane complexes are associated with pathogenicity and bacterial fitness. Understanding of these large assemblies has exponentially increased in the last few years thanks to electron microscopy. In fact, a revolution in this field has led to breakthroughs in characterizing the structures of secretion systems and other macromolecular machineries so as to obtain high-resolution images of complexes that could not be crystallized. In this review, we give a brief overview of structural advancements in the understanding of secretion systems, focusing in particular on cryo-electron microscopy, whether tomography or single-particle analysis. We describe how such techniques have contributed to knowledge of the mechanism of macromolecule secretion in bacteria and the impact they will have in the future.}, } @article {pmid30004126, year = {2018}, author = {Henshaw, JM and Jennions, MD and Kruuk, LEB}, title = {How to quantify (the response to) sexual selection on traits.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1904-1917}, doi = {10.1111/evo.13554}, pmid = {30004126}, issn = {1558-5646}, abstract = {Natural selection operates via fitness components like mating success, fecundity, and longevity, which can be understood as intermediaries in the causal process linking traits to fitness. In particular, sexual selection occurs when traits influence mating or fertilization success, which, in turn, influences fitness. We show how to quantify both these steps in a single path analysis, leading to better estimates of the strength of sexual selection. Our model controls for confounding variables, such as body size or condition, when estimating the relationship between mating and reproductive success. Correspondingly, we define the Bateman gradient and the Jones index using partial rather than simple regressions, which better captures how they are commonly interpreted. The model can be applied both to purely phenotypic data and to quantitative genetic parameters estimated using information on relatedness. The phenotypic approach breaks down selection differentials into a sexually selected and a "remainder" component. The quantitative genetic approach decomposes the estimated evolutionary response to selection analogously. We apply our method to analyze sexual selection in male dusky pipefish, Syngnathus floridae, and in two simulated datasets. We highlight conceptual and statistical limitations of previous path-based approaches, which can lead to substantial misestimation of sexual selection.}, } @article {pmid30004122, year = {2018}, author = {Ho, EKH and Agrawal, AF}, title = {Mutation accumulation in selfing populations under fluctuating selection.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1759-1772}, doi = {10.1111/evo.13553}, pmid = {30004122}, issn = {1558-5646}, support = {2015-05387//NSERC/ ; }, abstract = {Selfing species are prone to extinction, possibly because highly selfing populations can suffer from a continuous accumulation of deleterious mutations, a process analogous to Muller's ratchet in asexual populations. However, current theory provides little insight into which types of genes are most likely to accumulate deleterious alleles and what environmental circumstances may accelerate genomic degradation. Here, we investigate temporal changes in the environment that cause fluctuations in the strength of purifying selection. We simulate selfing populations with genomes containing a mixture of loci experiencing constant selection and loci experiencing selection that fluctuates in strength (but not direction). Even when both types of loci experience the same average strength of selection, loci under fluctuating selection contribute disproportionately more to deleterious mutation accumulation. Moreover, the presence of loci experiencing fluctuating selection in the genome increases the deleterious fixation rate at loci under constant selection; under most realistic scenarios, this effect of linked selection can be attributed to a reduction in Ne . Fluctuating selection is particularly injurious when selective environments are strongly autocorrelated over time and when selection is concentrated into rare bouts of strong selection. These results imply that loci under fluctuating selection are likely important drivers of extinction in selfing species.}, } @article {pmid30004011, year = {2018}, author = {Stokkan, M and Jurado-Rivera, JA and Oromí, P and Juan, C and Jaume, D and Pons, J}, title = {Species delimitation and mitogenome phylogenetics in the subterranean genus Pseudoniphargus (Crustacea: Amphipoda).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {988-999}, doi = {10.1016/j.ympev.2018.07.002}, pmid = {30004011}, issn = {1095-9513}, abstract = {The amphi-Atlantic distributions exhibited by many thalassoid stygobiont (obligate subterranean) crustaceans have been explained by fragmentation by plate tectonics of ancestral shallow water marine populations. The amphipod stygobiont genus Pseudoniphargus is distributed across the Mediterranean region but also in the North Atlantic archipelagos of Bermuda, Azores, Madeira and the Canaries. We used species delimitation methods and mitogenome phylogenetic analyses to clarify the species diversity and evolutionary relationships within the genus and timing their diversification. Analyses included samples from the Iberian Peninsula, northern Morocco, the Balearic, Canarian, Azores and Madeira archipelagoes plus Bermuda. In most instances, morphological and molecular-based species delimitation analyses yielded consistent results. Notwithstanding, in a few cases either incipient speciation with no involvement of detectable morphological divergence or species crypticism were the most plausible explanations for the disagreement found between morphological and molecular species delimitations. Phylogenetic analyses based on a robust calibrated mitochondrial tree suggested that Pseudoniphargus lineages have a younger age than for other thalassoid amphipods displaying a disjunct distribution embracing both sides of the Atlantic Ocean. A major split within the family was estimated to occur at the Paleocene, when a lineage from Northern Iberian Peninsula diverged from the rest of pseudoniphargids. Species diversification in the peri-Mediterranean area was deduced to occur in early Miocene to Tortonian times, while in the Atlantic islands it started in the Pliocene. Our results show that the current distribution pattern of Pseudoniphargus resulted from a complex admix of relatively ancient vicariance events and several episodes of long- distance dispersal.}, } @article {pmid30003961, year = {2018}, author = {Rodrigues-Costa, F and Cayô, R and Matos, AP and Girardello, R and Martins, WMBS and Carrara-Marroni, FE and Gales, AC}, title = {Temporal evolution of Acinetobacter baumannii ST107 clone: conversion of blaOXA-143 into blaOXA-231 coupled with mobilization of ISAba1 upstream occAB1.}, journal = {Research in microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.resmic.2018.07.001}, pmid = {30003961}, issn = {1769-7123}, abstract = {Nine carbapenem-resistant Acinetobacter baumannii isolates carrying blaOXA-231 and an ISAba1 upstream occAB1 were evaluated. They were clonally related and belonged to ST107. An OXA-143-producing A. baumannii ST107 strain (Ac-148) that did not possess ISAba1 upstream occAB1 was included in the analysis. Reduction in the expression of occAB1 and a 4-fold increase of carbapenem MICs were observed for all isolates, except for the Ac-148 strain, probably due to the presence of ISAba1 upstream occAB1 but in the same transcriptional orientation. We reported an A. baumannii ST107 clone carrying blaOXA-143 that acquired a mutation resulting into blaOXA-231 and mobilized ISAba1 upstream occAB1.}, } @article {pmid30003663, year = {2018}, author = {Butaitė, E and Kramer, J and Wyder, S and Kümmerli, R}, title = {Environmental determinants of pyoverdine production, exploitation and competition in natural Pseudomonas communities.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3629-3642}, doi = {10.1111/1462-2920.14355}, pmid = {30003663}, issn = {1462-2920}, support = {139164//Swiss National Science Foundation/ ; 165835//Swiss National Science Foundation/ ; //Forschungskredit of the University of Zurich/ ; }, abstract = {Many bacteria rely on the secretion of siderophores to scavenge iron from the environment. Laboratory studies revealed that abiotic and biotic factors together determine how much siderophores bacteria make, and whether siderophores can be exploited by non-producing cheaters or be deployed by producers to inhibit competitors. Here, we explore whether these insights apply to natural communities, by comparing the production of the siderophore pyoverdine among 930 Pseudomonas strains from 48 soil and pond communities. We found that pH, iron content, carbon concentration and community diversity determine pyoverdine production levels, and the extent to which strains are either stimulated or inhibited by heterologous (non-self) pyoverdines. While pyoverdine non-producers occurred in both habitats, their prevalence was higher in soils. Environmental and genetic analyses suggest that non-producers can evolve as cheaters, exploiting heterologous pyoverdine, but also due to pyoverdine disuse in environments with increased iron availability. Overall, we found that environmental factors explained between-strain variation in pyoverdine production much better in soils than in ponds, presumably because high strain mixing in ponds impedes local adaption. Our study sheds light on the complexity of natural bacterial communities, and provides first insights into the multivariate nature of siderophore-based iron acquisition and competition among environmental pseudomonads.}, } @article {pmid30003650, year = {2018}, author = {Kremp, F and Poehlein, A and Daniel, R and Müller, V}, title = {Methanol metabolism in the acetogenic bacterium Acetobacterium woodii.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4369-4384}, doi = {10.1111/1462-2920.14356}, pmid = {30003650}, issn = {1462-2920}, support = {741791//European Research Council/International ; }, abstract = {Methanol derived from plant tissue is ubiquitous in anaerobic sediments and a good substrate for anaerobes growing on C1 compounds such as methanogens and acetogens. In contrast to methanogens little is known about the physiology, biochemistry and bioenergetics of methanol utilization in acetogenic bacteria. To fill this gap, we have used the model acetogen Acetobacterium woodii to study methanol metabolism using physiological and biochemical experiments paired with molecular studies and transcriptome analysis. These studies identified the genes and enzymes involved in acetogenesis from methanol and the redox carriers involved. We will present the first comprehensive model for carbon and electron flow from methanol in an acetogen and the bioenergetics of acetogenesis from methanol.}, } @article {pmid30003649, year = {2018}, author = {Aalto, SL and Saarenheimo, J and Mikkonen, A and Rissanen, AJ and Tiirola, M}, title = {Resistant ammonia-oxidizing archaea endure, but adapting ammonia-oxidizing bacteria thrive in boreal lake sediments receiving nutrient-rich effluents.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3616-3628}, pmid = {30003649}, issn = {1462-2920}, support = {286642310302//Biotieteiden ja Ympäristön Tutkimuksen Toimikunta/ ; LIFE12 ENV/FI/597 (N-SINK)//European Commission/ ; 615146//European Research Council/International ; 286642//Academy of Finland/ ; 310302//Academy of Finland/ ; 260797//Academy of Finland/ ; }, abstract = {Climate change along with anthropogenic activities changes biogeochemical conditions in lake ecosystems, modifying the sediment microbial communities. Wastewater effluents introduce nutrients and organic material but also novel microbes to lake ecosystems, simulating forthcoming increases in catchment loadings. In this work, we first used 16s rRNA gene sequencing to study how the overall sediment microbial community responds to wastewater in six boreal lakes. To examine forthcoming changes in the lake biogeochemistry, we focused on the ammonia-oxidizing archaea (AOA) and bacteria (AOB), and examined their functional and compositional community response to wastewater. Although we found the least diverse and least resistant prokaryotic communities from the most wastewater-influenced sediments, the community changed fast toward the natural composition with the diminishing influence of wastewater. Each lake hosted a unique resistant AOA community, while AOB communities were adapting, responding to environmental conditions as well as receiving new members from WWTPs. In general, AOB dominated in numbers in wastewater-influenced sediments, while the ratio between AOA and AOB increased when moving toward pristine conditions. Our results suggest that although future climate-change-driven increases in nutrient loading and microbial migration might significantly disrupt lake sediment microbiomes, they can promote nitrification through adapting and abundant AOB communities.}, } @article {pmid30003647, year = {2018}, author = {Hao, Z and Li, L and Fu, Y and Liu, H}, title = {The influence of bioregenerative life-support system dietary structure and lifestyle on the gut microbiota: a 105-day ground-based space simulation in Lunar Palace 1.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3643-3656}, doi = {10.1111/1462-2920.14358}, pmid = {30003647}, issn = {1462-2920}, support = {2012DFR30570//International Science and Technology Cooperation Program/ ; }, abstract = {Understanding the dynamics of human gut microbiota in space is crucial in maintaining astronaut health. Long-duration and deep-space manned exploration will require the in situ regeneration of resources, which would be achieved by an artificial ecosystem, such as a bioregenerative life-support system (BLSS). Potential response of human gut microbiota to particular lifestyle and dietary structure experienced in a BLSS remains unclear. Here, we report how a BLSS impacts the gut microbiota during a 105-day study that took place in the Chinese Lunar Palace 1 (LP1). The three crewmembers were provided with high-plant and high-fibre diet, and they followed a fixed schedule including extensive labour in the plant cabin. The gut microbiota composition of the three crewmembers showed convergence and similar dynamic change. Increased diversity and abundance of Lachnospira, Faecalibacterium and Blautia indicated that the LP1 dietary structure and the lifestyle may be beneficial for the maintenance of healthy gut microbiome. A stronger impact was found from the gut microbiome to the environment compared with the opposite direction, suggesting the necessity of environmental pathogen control in BLSS.}, } @article {pmid30003645, year = {2018}, author = {Probst, M and Gómez-Brandón, M and Bardelli, T and Egli, M and Insam, H and Ascher-Jenull, J}, title = {Bacterial communities of decaying Norway spruce follow distinct slope exposure and time-dependent trajectories.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3657-3670}, doi = {10.1111/1462-2920.14359}, pmid = {30003645}, issn = {1462-2920}, support = {2017/3/BIO-1//University of Innsbruck (Austria)/ ; DT16364//University of Florence (Italy)/ ; RYC-2016-21231//Ministerio de Economía y Competitividad/ ; I989-B16//Fonds zur Förderung der wissenschaftlichen Forschung/ ; }, abstract = {Deadwood decay employs a complex metabolism and provides carbon and nutrients for soils. Although being highly diverse, the contribution of the bacterial deadwood colonizing community is underexplored compared with the fungal one. Therefore, we performed an in-field mesocosm study and monitored the bacterial communities in decaying experimental Picea abies wood blocks and their underlying soil on north- and south- exposed slopes in the Italian Alps over a 2-year period. The faster deadwood decay at the south-facing slope was associated with a higher bacterial richness and a higher number of specialist operational taxonomic units (OTUs) which were more strongly correlated to environmental parameters than other bacterial community members. With progressing decay, the wood and soil bacterial communities became more similar in terms of richness, diversity and evenness and especially at the south-facing slope, they also became more similar in terms of community composition. Exposure-specific OTUs suggest wood-soil interaction. However, despite the strong influence of exposure on the soil bacterial communities, the P. abies wood blocks shared a comparably high number of OTUs with the soil irrespective of the slope. At finer taxonomic scale, we identified Pseudomonas, Microbacteria, Sphingomonas, Xanthomonas, Methylovirgula and Burkholderia as decay associated, although their functional role needs further studies.}, } @article {pmid30003537, year = {2018}, author = {Cahenzli, F and Bonetti, C and Erhardt, A}, title = {Divergent strategies in pre- and postzygotic reproductive isolation between two closely related Dianthus species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1851-1862}, doi = {10.1111/evo.13556}, pmid = {30003537}, issn = {1558-5646}, support = {3100AO-108271/1//Swiss National Science Foundation/ ; }, abstract = {Quantifying the relative contribution of multiple isolation barriers to gene flow between recently diverged species is essential for understanding speciation processes. In parapatric populations, local adaptation is thought to be a major contributor to the evolution of reproductive isolation. However, extrinsic postzygotic barriers assessed in reciprocal transplant experiments are often neglected in empirical assessments of multiple isolation barriers. We analyzed multiple isolation barriers between two closely related species of the plant genus Dianthus, a genus characterized by the most rapid species diversification in plants reported so far. Although D. carthusianorum L. and D. sylvestris Wulf. can easily be hybridized in crossing experiments, natural hybrids are rare. We found that in parapatry, pollinator-mediated prezygotic reproductive isolation barriers are important for both D. carthusianorum (0.761) and D. sylvestris (0.468). In contrast to D. carthusianorum, high hybrid viability in D. sylvestris (-0.491) was counteracted by strong extrinsic postzygotic isolation (0.900). Our study highlights the importance of including reciprocal transplant experiments for documenting extrinsic postzygotic isolation and demonstrates clearly divergent strategies and hence asymmetric pre- and postzygotic reproductive isolation between closely related species. It also suggests that pollinator-mediated and ecological isolation could have interacted in synergistic ways, further stimulating rapid speciation in Dianthus.}, } @article {pmid30002563, year = {2018}, author = {Hawley, RJ}, title = {Making Stream Restoration More Sustainable: A Geomorphically, Ecologically, and Socioeconomically Principled Approach to Bridge the Practice with the Science.}, journal = {Bioscience}, volume = {68}, number = {7}, pages = {517-528}, pmid = {30002563}, issn = {0006-3568}, abstract = {Despite large advances in the state of the science of stream ecology and river mechanics, the practitioner-driven field of stream restoration remains plagued by narrowly focused projects that sometimes even fail to improve aquatic habitat or geomorphic stability-two nearly universal project goals. The intent of this article is to provide an accessible framework that bridges that gap between the current state of practice and a more geomorphically robust and ecologically holistic foundation that also provides better accounting of socioeconomic factors in support of more sustainable stream restoration outcomes. It points to several more comprehensive design references and presents some simple strategies that could be used to protect against common failure mechanisms of ubiquitous design approaches (i.e., regional curves, Rosgen planform, and grade control). From the simple structure design to the watershed-scale restoration program, this may be a first step toward a more geomorphically principled, ecologically holistic, and socioeconomically sustainable field.}, } @article {pmid30002505, year = {2018}, author = {Du, D and Wang-Kan, X and Neuberger, A and van Veen, HW and Pos, KM and Piddock, LJV and Luisi, BF}, title = {Multidrug efflux pumps: structure, function and regulation.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {523-539}, doi = {10.1038/s41579-018-0048-6}, pmid = {30002505}, issn = {1740-1534}, abstract = {Infections arising from multidrug-resistant pathogenic bacteria are spreading rapidly throughout the world and threaten to become untreatable. The origins of resistance are numerous and complex, but one underlying factor is the capacity of bacteria to rapidly export drugs through the intrinsic activity of efflux pumps. In this Review, we describe recent advances that have increased our understanding of the structures and molecular mechanisms of multidrug efflux pumps in bacteria. Clinical and laboratory data indicate that efflux pumps function not only in the drug extrusion process but also in virulence and the adaptive responses that contribute to antimicrobial resistance during infection. The emerging picture of the structure, function and regulation of efflux pumps suggests opportunities for countering their activities.}, } @article {pmid30002470, year = {2018}, author = {Tollefson, J}, title = {Science under siege: behind the scenes at Trump's troubled environment agency.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {316-319}, doi = {10.1038/d41586-018-05706-9}, pmid = {30002470}, issn = {1476-4687}, } @article {pmid30002255, year = {2018}, author = {Evans, T}, title = {Heed the call to change.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {198}, doi = {10.1126/science.361.6398.198}, pmid = {30002255}, issn = {1095-9203}, } @article {pmid30002254, year = {2018}, author = {Reichmann, J and Nijmeijer, B and Hossain, MJ and Eguren, M and Schneider, I and Politi, AZ and Roberti, MJ and Hufnagel, L and Hiiragi, T and Ellenberg, J}, title = {Dual-spindle formation in zygotes keeps parental genomes apart in early mammalian embryos.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {189-193}, doi = {10.1126/science.aar7462}, pmid = {30002254}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Anaphase ; Animals ; Blastomeres/cytology ; Cell Nucleus/metabolism ; *Chromosome Segregation ; Embryo, Mammalian/*embryology ; Female ; Genome ; Male ; Maternal Inheritance/*genetics ; Mice ; Mice, Inbred C3H ; Mice, Inbred C57BL ; Microtubules/metabolism ; Paternal Inheritance/*genetics ; Spindle Poles/*metabolism ; Zygote/*metabolism ; }, abstract = {At the beginning of mammalian life, the genetic material from each parent meets when the fertilized egg divides. It was previously thought that a single microtubule spindle is responsible for spatially combining the two genomes and then segregating them to create the two-cell embryo. We used light-sheet microscopy to show that two bipolar spindles form in the zygote and then independently congress the maternal and paternal genomes. These two spindles aligned their poles before anaphase but kept the parental genomes apart during the first cleavage. This spindle assembly mechanism provides a potential rationale for erroneous divisions into more than two blastomeric nuclei observed in mammalian zygotes and reveals the mechanism behind the observation that parental genomes occupy separate nuclear compartments in the two-cell embryo.}, } @article {pmid30002253, year = {2018}, author = {Kuroha, T and Nagai, K and Gamuyao, R and Wang, DR and Furuta, T and Nakamori, M and Kitaoka, T and Adachi, K and Minami, A and Mori, Y and Mashiguchi, K and Seto, Y and Yamaguchi, S and Kojima, M and Sakakibara, H and Wu, J and Ebana, K and Mitsuda, N and Ohme-Takagi, M and Yanagisawa, S and Yamasaki, M and Yokoyama, R and Nishitani, K and Mochizuki, T and Tamiya, G and McCouch, SR and Ashikari, M}, title = {Ethylene-gibberellin signaling underlies adaptation of rice to periodic flooding.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {181-186}, doi = {10.1126/science.aat1577}, pmid = {30002253}, issn = {1095-9203}, mesh = {*Adaptation, Physiological ; Alleles ; Ethylenes/*metabolism ; *Floods ; Genes, Plant/*physiology ; Gibberellins/genetics/*physiology ; Haplotypes ; Oryza/genetics/*growth & development ; Transcription Factors/genetics/*physiology ; }, abstract = {Most plants do poorly when flooded. Certain rice varieties, known as deepwater rice, survive periodic flooding and consequent oxygen deficiency by activating internode growth of stems to keep above the water. Here, we identify the gibberellin biosynthesis gene, SD1 (SEMIDWARF1), whose loss-of-function allele catapulted the rice Green Revolution, as being responsible for submergence-induced internode elongation. When submerged, plants carrying the deepwater rice-specific SD1 haplotype amplify a signaling relay in which the SD1 gene is transcriptionally activated by an ethylene-responsive transcription factor, OsEIL1a. The SD1 protein directs increased synthesis of gibberellins, largely GA4, which promote internode elongation. Evolutionary analysis shows that the deepwater rice-specific haplotype was derived from standing variation in wild rice and selected for deepwater rice cultivation in Bangladesh.}, } @article {pmid30002252, year = {2018}, author = {Sweis, BM and Abram, SV and Schmidt, BJ and Seeland, KD and MacDonald, AW and Thomas, MJ and Redish, AD}, title = {Sensitivity to "sunk costs" in mice, rats, and humans.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {178-181}, doi = {10.1126/science.aar8644}, pmid = {30002252}, issn = {1095-9203}, support = {T32 GM008244/GM/NIGMS NIH HHS/United States ; F31 DA040335/DA/NIDA NIH HHS/United States ; R01 DA041808/DA/NIDA NIH HHS/United States ; F30 DA043326/DA/NIDA NIH HHS/United States ; T32 GM008471/GM/NIGMS NIH HHS/United States ; R01 MH084861/MH/NIMH NIH HHS/United States ; R01 DA030672/DA/NIDA NIH HHS/United States ; R01 DA019666/DA/NIDA NIH HHS/United States ; F32 DA038392/DA/NIDA NIH HHS/United States ; R01 MH080318/MH/NIMH NIH HHS/United States ; K02 DA035459/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; *Cognition ; *Cost-Benefit Analysis ; *Decision Making ; Economics, Behavioral ; Humans ; Mice ; Rats ; Reward ; }, abstract = {Sunk costs are irrecoverable investments that should not influence decisions, because decisions should be made on the basis of expected future consequences. Both human and nonhuman animals can show sensitivity to sunk costs, but reports from across species are inconsistent. In a temporal context, a sensitivity to sunk costs arises when an individual resists ending an activity, even if it seems unproductive, because of the time already invested. In two parallel foraging tasks that we designed, we found that mice, rats, and humans show similar sensitivities to sunk costs in their decision-making. Unexpectedly, sensitivity to time invested accrued only after an initial decision had been made. These findings suggest that sensitivity to temporal sunk costs lies in a vulnerability distinct from deliberation processes and that this distinction is present across species.}, } @article {pmid30002251, year = {2018}, author = {Roque, JB and Kuroda, Y and Göttemann, LT and Sarpong, R}, title = {Deconstructive fluorination of cyclic amines by carbon-carbon cleavage.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {171-174}, pmid = {30002251}, issn = {1095-9203}, support = {R01 GM086374/GM/NIGMS NIH HHS/United States ; }, abstract = {Deconstructive functionalizations involving scission of carbon-carbon double bonds are well established. In contrast, unstrained C(sp3)-C(sp3) bond cleavage and functionalization have less precedent. Here we report the use of deconstructive fluorination to access mono- and difluorinated amine derivatives by C(sp3)-C(sp3) bond cleavage in saturated nitrogen heterocycles such as piperidines and pyrrolidines. Silver-mediated ring-opening fluorination using Selectfluor highlights a strategy for cyclic amine functionalization and late-stage skeletal diversification, establishing cyclic amines as synthons for amino alkyl radicals and providing synthetic routes to valuable building blocks.}, } @article {pmid30002250, year = {2018}, author = {Harris, R and Sato, Y and Berkley, AJ and Reis, M and Altomare, F and Amin, MH and Boothby, K and Bunyk, P and Deng, C and Enderud, C and Huang, S and Hoskinson, E and Johnson, MW and Ladizinsky, E and Ladizinsky, N and Lanting, T and Li, R and Medina, T and Molavi, R and Neufeld, R and Oh, T and Pavlov, I and Perminov, I and Poulin-Lamarre, G and Rich, C and Smirnov, A and Swenson, L and Tsai, N and Volkmann, M and Whittaker, J and Yao, J}, title = {Phase transitions in a programmable quantum spin glass simulator.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {162-165}, doi = {10.1126/science.aat2025}, pmid = {30002250}, issn = {1095-9203}, abstract = {Understanding magnetic phases in quantum mechanical systems is one of the essential goals in condensed matter physics, and the advent of prototype quantum simulation hardware has provided new tools for experimentally probing such systems. We report on the experimental realization of a quantum simulation of interacting Ising spins on three-dimensional cubic lattices up to dimensions 8 × 8 × 8 on a D-Wave processor (D-Wave Systems, Burnaby, Canada). The ability to control and read out the state of individual spins provides direct access to several order parameters, which we used to determine the lattice's magnetic phases as well as critical disorder and one of its universal exponents. By tuning the degree of disorder and effective transverse magnetic field, we observed phase transitions between a paramagnetic, an antiferromagnetic, and a spin-glass phase.}, } @article {pmid30002249, year = {2018}, author = {Ye, HY and Tang, YY and Li, PF and Liao, WQ and Gao, JX and Hua, XN and Cai, H and Shi, PP and You, YM and Xiong, RG}, title = {Metal-free three-dimensional perovskite ferroelectrics.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {151-155}, doi = {10.1126/science.aas9330}, pmid = {30002249}, issn = {1095-9203}, abstract = {Inorganic perovskite ferroelectrics are widely used in nonvolatile memory elements, capacitors, and sensors because of their excellent ferroelectric and other properties. Organic ferroelectrics are desirable for their mechanical flexibility, low weight, environmentally friendly processing, and low processing temperatures. Although almost a century has passed since the first ferroelectric, Rochelle salt, was discovered, examples of highly desirable organic perovskite ferroelectrics are lacking. We found a family of metal-free organic perovskite ferroelectrics with the characteristic three-dimensional structure, among which MDABCO (N-methyl-N'-diazabicyclo[2.2.2]octonium)-ammonium triiodide has a spontaneous polarization of 22 microcoulombs per square centimeter [close to that of barium titanate (BTO)], a high phase transition temperature of 448 kelvins (above that of BTO), and eight possible polarization directions. These attributes make it attractive for use in flexible devices, soft robotics, biomedical devices, and other applications.}, } @article {pmid30002248, year = {2018}, author = {, }, title = {Neutrino emission from the direction of the blazar TXS 0506+056 prior to the IceCube-170922A alert.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {147-151}, doi = {10.1126/science.aat2890}, pmid = {30002248}, issn = {1095-9203}, abstract = {A high-energy neutrino event detected by IceCube on 22 September 2017 was coincident in direction and time with a gamma-ray flare from the blazar TXS 0506+056. Prompted by this association, we investigated 9.5 years of IceCube neutrino observations to search for excess emission at the position of the blazar. We found an excess of high-energy neutrino events, with respect to atmospheric backgrounds, at that position between September 2014 and March 2015. Allowing for time-variable flux, this constitutes 3.5σ evidence for neutrino emission from the direction of TXS 0506+056, independent of and prior to the 2017 flaring episode. This suggests that blazars are identifiable sources of the high-energy astrophysical neutrino flux.}, } @article {pmid30002247, year = {2018}, author = {Iversen, LL and Bendixen, M}, title = {Funding agencies can prevent harassment.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {140}, doi = {10.1126/science.aau3979}, pmid = {30002247}, issn = {1095-9203}, mesh = {*Financial Management ; Humans ; Sexual Harassment/*prevention & control ; }, } @article {pmid30002246, year = {2018}, author = {Buchanan, GM and Beresford, AE and Hebblewhite, M and Escobedo, FJ and De Klerk, HM and Donald, PF and Escribano, P and Koh, LP and Martínez-López, J and Pettorelli, N and Skidmore, AK and Szantoi, Z and Tabor, K and Wegmann, M and Wich, S}, title = {Free satellite data key to conservation.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {139-140}, doi = {10.1126/science.aau2650}, pmid = {30002246}, issn = {1095-9203}, mesh = {*Biodiversity ; *Conservation of Natural Resources ; *Environmental Monitoring ; *Satellite Imagery ; }, } @article {pmid30002245, year = {2018}, author = {Brito, MFG and Magalhães, ALB and Lima-Junior, DP and Pelicice, FM and Azevedo-Santos, VM and Garcia, DAZ and Cunico, AM and Vitule, JRS}, title = {Brazil naturalizes non-native species.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {139}, doi = {10.1126/science.aau3368}, pmid = {30002245}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; Brazil ; *Fishes ; Introduced Species/*legislation & jurisprudence ; *Rana catesbeiana ; }, } @article {pmid30002244, year = {2018}, author = {Guerrini, CJ and Majumder, MA and Lewellyn, MJ and McGuire, AL}, title = {Citizen science, public policy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {134-136}, doi = {10.1126/science.aar8379}, pmid = {30002244}, issn = {1095-9203}, support = {K01 HG009355/HG/NHGRI NIH HHS/United States ; }, } @article {pmid30002243, year = {2018}, author = {Nissen, P}, title = {Jens Christian Skou (1918-2018).}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {133}, doi = {10.1126/science.aau5275}, pmid = {30002243}, issn = {1095-9203}, mesh = {Biochemistry/*history ; Denmark ; History, 20th Century ; History, 21st Century ; Membrane Proteins/*history ; }, } @article {pmid30002242, year = {2018}, author = {Li, W and Ji, LJ}, title = {Perovskite ferroelectrics go metal free.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {132}, doi = {10.1126/science.aat5729}, pmid = {30002242}, issn = {1095-9203}, } @article {pmid30002241, year = {2018}, author = {Cotton, JA and Berriman, M and Dalén, L and Barnes, I}, title = {Eradication genomics-lessons for parasite control.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {130-131}, doi = {10.1126/science.aar6609}, pmid = {30002241}, issn = {1095-9203}, mesh = {Disease Eradication/*methods ; Genomics ; Humans ; Neglected Diseases/*parasitology/*prevention & control ; Parasitic Diseases/*prevention & control ; Pest Control, Biological/*methods ; }, } @article {pmid30002240, year = {2018}, author = {Zielinska, AP and Schuh, M}, title = {Double trouble at the beginning of life.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {128-129}, doi = {10.1126/science.aau3216}, pmid = {30002240}, issn = {1095-9203}, mesh = {*Beginning of Human Life ; *Life ; }, } @article {pmid30002239, year = {2018}, author = {Moffat, K}, title = {Femtosecond structural photobiology.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {127-128}, doi = {10.1126/science.aau3200}, pmid = {30002239}, issn = {1095-9203}, } @article {pmid30002238, year = {2018}, author = {Nagy, LG}, title = {Many roads to convergence.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {125-126}, doi = {10.1126/science.aau2409}, pmid = {30002238}, issn = {1095-9203}, } @article {pmid30002237, year = {2018}, author = {Brosnan, SF}, title = {When persistence doesn't pay.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {124-125}, doi = {10.1126/science.aau3144}, pmid = {30002237}, issn = {1095-9203}, } @article {pmid30002236, year = {2018}, author = {Service, RF}, title = {Liquid sunshine.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {120-123}, doi = {10.1126/science.361.6398.120}, pmid = {30002236}, issn = {1095-9203}, } @article {pmid30002235, year = {2018}, author = {Pennisi, E and Price, M}, title = {Molecular 'barcodes' reveal lost whale hunts.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {119}, doi = {10.1126/science.361.6398.119}, pmid = {30002235}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; Bone and Bones ; *DNA Barcoding, Taxonomic ; DNA, Ancient ; Phylogeny ; Whales/*classification/*genetics ; }, } @article {pmid30002234, year = {2018}, author = {Cohen, J}, title = {A 'gene drive' makes its debut in mammals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {118}, doi = {10.1126/science.361.6398.118}, pmid = {30002234}, issn = {1095-9203}, mesh = {Animals ; *CRISPR-Cas Systems ; *Gene Drive Technology ; Gene Editing/*methods ; Mice ; Mice, Inbred Strains/*genetics ; }, } @article {pmid30002233, year = {2018}, author = {Zainzinger, V}, title = {Digital chemical test impresses.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {117}, doi = {10.1126/science.361.6398.117}, pmid = {30002233}, issn = {1095-9203}, mesh = {Animal Use Alternatives/*methods ; Animals ; Computers ; Databases, Chemical/*statistics & numerical data ; Toxicity Tests/*methods ; }, } @article {pmid30002232, year = {2018}, author = {Normile, D}, title = {China announces new flotilla of space science missions.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {116-117}, doi = {10.1126/science.361.6398.116}, pmid = {30002232}, issn = {1095-9203}, } @article {pmid30002231, year = {2018}, author = {Clery, D}, title = {Ice reveals a messenger from a blazing galaxy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {115-116}, doi = {10.1126/science.361.6398.115}, pmid = {30002231}, issn = {1095-9203}, } @article {pmid30002230, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {112-114}, doi = {10.1126/science.361.6398.112}, pmid = {30002230}, issn = {1095-9203}, } @article {pmid30002229, year = {2018}, author = {Moro-Martín, A}, title = {Spain's good news.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {111}, doi = {10.1126/science.aau6630}, pmid = {30002229}, issn = {1095-9203}, } @article {pmid30002228, year = {2018}, author = {Halls, AS and Moyle, PB}, title = {Comment on "Designing river flows to improve food security futures in the Lower Mekong Basin".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {}, doi = {10.1126/science.aat1989}, pmid = {30002228}, issn = {1095-9203}, mesh = {Fisheries ; *Food Supply ; *Rivers ; }, abstract = {The designer flow regime proposed by Sabo et al (Research Articles, 8 December 2017, p. 1270) to support fisheries in the Lower Mekong Basin fails to account for important ecological, political, and economic dimensions. In doing so, they indicate that dam impacts can be easily mitigated. Such an action would serve to increase risks to food and livelihood futures in the basin.}, } @article {pmid30002227, year = {2018}, author = {Holtgrieve, GW and Arias, ME and Ruhi, A and Elliott, V and Nam, S and Ngor, PB and Räsänen, TA and Sabo, JL}, title = {Response to Comments on "Designing river flows to improve food security futures in the Lower Mekong Basin".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {}, doi = {10.1126/science.aat1477}, pmid = {30002227}, issn = {1095-9203}, mesh = {Fisheries ; *Food Supply ; Hydrology ; *Rivers ; }, abstract = {Sabo et al presented an empirically derived algorithm defining the socioecological response of the Tonle Sap Dai fishery in the Cambodian Mekong to basin-scale variation in hydrologic flow regime. Williams suggests that the analysis leading to the algorithm is flawed because of the large distance between the gauge used to measure water levels (hydrology) and the site of harvest for the fishery. Halls and Moyle argue that Sabo et al's findings are well known and contend that the algorithm is not a comprehensive assessment of sustainability. We argue that Williams' critique stems from a misunderstanding about our analysis; further clarification of the analysis is provided. We regret not citing more of the work indicated by Halls and Moyle, yet we note that our empirical analysis provides additional new insights into Mekong flow-fishery relationships.}, } @article {pmid30002226, year = {2018}, author = {, and , and , and , and , and , and , and , and , and , and , and , and , and , and , and , }, title = {Multimessenger observations of a flaring blazar coincident with high-energy neutrino IceCube-170922A.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {}, doi = {10.1126/science.aat1378}, pmid = {30002226}, issn = {1095-9203}, abstract = {Previous detections of individual astrophysical sources of neutrinos are limited to the Sun and the supernova 1987A, whereas the origins of the diffuse flux of high-energy cosmic neutrinos remain unidentified. On 22 September 2017, we detected a high-energy neutrino, IceCube-170922A, with an energy of ~290 tera-electron volts. Its arrival direction was consistent with the location of a known γ-ray blazar, TXS 0506+056, observed to be in a flaring state. An extensive multiwavelength campaign followed, ranging from radio frequencies to γ-rays. These observations characterize the variability and energetics of the blazar and include the detection of TXS 0506+056 in very-high-energy γ-rays. This observation of a neutrino in spatial coincidence with a γ-ray-emitting blazar during an active phase suggests that blazars may be a source of high-energy neutrinos.}, } @article {pmid30002225, year = {2018}, author = {Williams, JG}, title = {Comment on "Designing river flows to improve food security futures in the Lower Mekong Basin".}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {}, doi = {10.1126/science.aat1225}, pmid = {30002225}, issn = {1095-9203}, mesh = {Fisheries ; *Food Supply ; Forecasting ; *Rivers ; }, abstract = {Sabo et al (Research Articles, 8 December 2017, p. 1270) use sophisticated analyses of flow and fishery data from the Lower Mekong Basin to design a "good" hydrograph that, if implemented by planned hydropower dams, would increase the catch by a factor of 3.7. However, the hydrograph is not implementable, and, if it were, it would devastate the fishery. Further, the analyses are questionable.}, } @article {pmid30001870, year = {2018}, author = {Elliott, MC and Quam, R and Nalla, S and de Ruiter, DJ and Hawks, J and Berger, LR}, title = {Description and analysis of three Homo naledi incudes from the Dinaledi Chamber, Rising Star cave (South Africa).}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {146-155}, doi = {10.1016/j.jhevol.2018.06.008}, pmid = {30001870}, issn = {1095-8606}, abstract = {This study describes three incudes recovered from the Dinaledi Chamber in the Rising Star cave system in South Africa. All three bones were recovered during sieving of excavated sediments and likely represent three Homo naledi individuals. Morphologically and metrically, the Dinaledi ossicles resemble those of chimpanzees and Paranthropus robustus more than they do later members of the genus Homo, and fall outside of the modern human range of variation in several dimensions. Despite this, when overall size is considered, the functional lengths in H. naledi and P. robustus are very similar to those predicted for a human with a similar-sized incus. In this sense, both taxa seem to show a relatively elongated functional length, distinguishing them from chimpanzees. The functional length in H. naledi is slightly longer in absolute terms than in P. robustus, suggesting H. naledi may already show a slight increase in functional length compared with early hominins. While H. naledi lacks the more open angle between the long and short processes found in modern humans, considered a derived feature within the genus Homo, the value in H. naledi is similar to that predicted for a hominoid with a similar-sized incus. Principal components analysis of size-standardized variables shows H. naledi falling outside of the recent human range of variation, but within the confidence ellipse for gorillas. Phylogenetic polarity is complicated by the absence of incus data from early members of the genus Homo, but the generally primitive nature of the H. naledi incudes is consistent with other primitive features of the species, such as the very small cranial capacity. These ossicles add significantly to the understanding of incus variation in hominins and provide important new data on the morphology and taxonomic affinities of H. naledi.}, } @article {pmid30001854, year = {2018}, author = {Berry, D and Loy, A}, title = {Stable-Isotope Probing of Human and Animal Microbiome Function.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {999-1007}, pmid = {30001854}, issn = {1878-4380}, abstract = {Humans and animals host diverse communities of microorganisms important to their physiology and health. Despite extensive sequencing-based characterization of host-associated microbiomes, there remains a dramatic lack of understanding of microbial functions. Stable-isotope probing (SIP) is a powerful strategy to elucidate the ecophysiology of microorganisms in complex host-associated microbiotas. Here, we suggest that SIP methodologies should be more frequently exploited as part of a holistic functional microbiomics approach. We provide examples of how SIP has been used to study host-associated microbes in vivo and ex vivo. We highlight recent developments in SIP technologies and discuss future directions that will facilitate deeper insights into the function of human and animal microbiomes.}, } @article {pmid30001749, year = {2018}, author = {K R, J and M, R and M, D and R, S and Gad, A and K, J and P, MI and Manuel, AT and U C, AJ}, title = {Feature optimization in high dimensional chemical space: statistical and data mining solutions.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {463}, pmid = {30001749}, issn = {1756-0500}, mesh = {*Data Mining ; *Polypharmacology ; Principal Component Analysis ; }, abstract = {OBJECTIVES: The primary goal of this experiment is to prioritize molecular descriptors that control the activity of active molecules that could reduce the dimensionality produced during the virtual screening process. It also aims to: (1) develop a methodology for sampling large datasets and the statistical verification of the sampling process, (2) apply screening filter to detect molecules with polypharmacological or promiscuous activity.

RESULTS: Sampling from large a dataset and its verification were done by applying Z-test. Molecular descriptors were prioritized using principal component analysis (PCA) by eliminating the least influencing ones. The original dimensions were reduced to one-twelfth by the application of PCA. There was a significant improvement in statistical parameter values of virtual screening model which in turn resulted in better screening results. Further improvement of screened results was done by applying Eli Lilly MedChem rules filter that removed molecules with polypharmacological or promiscuous activity. It was also shown that similarities in the activity of compounds were due to the molecular descriptors which were not apparent in prima facie structural studies.}, } @article {pmid30001748, year = {2018}, author = {Wadunde, I and Tuhebwe, D and Ediau, M and Okure, G and Mpimbaza, A and Wanyenze, RK}, title = {Factors associated with adherence to antiretroviral therapy among HIV infected children in Kabale district, Uganda: a cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {466}, pmid = {30001748}, issn = {1756-0500}, support = {U2G GH000817/GH/CGH CDC HHS/United States ; }, mesh = {Adolescent ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active ; Caregivers ; Child ; Child, Preschool ; Cross-Sectional Studies ; Female ; HIV Infections/*drug therapy ; Humans ; Infant ; Infant, Newborn ; Male ; *Medication Adherence ; Uganda ; }, abstract = {OBJECTIVES: This study was set out to assess the level of adherence to antiretroviral therapy (ART) and its determinants among children receiving HIV treatment in Kabale district, south western Uganda, in order to inform interventions for improving pediatric ART adherence.

RESULTS: Overall, 79% (121/153) of the children did not miss ART doses over the 7 days. Caregiver forgetfulness was the major reason for missing ART doses, 37% (13/35). Other reasons included transportation costs to the health facilities, 17%, (6/35) and children sitting for examinations in schools. Older children (11-14 years) were more likely to adhere to ART than the younger ones (0-10 years) (AOR = 6.41, 95% CI 1.31-31.42). Caregivers, who knew their HIV status, had their children more adherent to ART than the caregivers of unknown HIV status (AOR = 21.64: 95% CI 1.09-428.28). A significant proportion of children in two facilities 21.5% (32/153) missed ART doses within the previous week. Support for providers to identify clues or reminders to take drugs, extending HIV testing to caregivers and innovative models of ART delivery that alleviate transport costs to caregivers and allow sufficient drugs for children in school could enhance drug adherence among children.}, } @article {pmid30001743, year = {2018}, author = {Geadas, C and Acuna-Villaorduna, C and Mercier, G and Kleinman, MB and Horsburgh, CR and Ellner, JJ and Jacobson, KR}, title = {FDG-PET/CT activity leads to the diagnosis of unsuspected TB: a retrospective study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {464}, pmid = {30001743}, issn = {1756-0500}, support = {U19 AI111276/AI/NIAID NIH HHS/United States ; U19AI111276//National Institute of Allergy and Infectious Diseases/ ; }, mesh = {Adult ; Aged ; Boston ; Fluorodeoxyglucose F18 ; HIV Infections ; Humans ; Latent Tuberculosis/*diagnostic imaging ; Male ; Middle Aged ; *Positron Emission Tomography Computed Tomography ; Positron-Emission Tomography ; Radiopharmaceuticals ; Retrospective Studies ; *Tomography, X-Ray Computed ; }, abstract = {OBJECTIVE: Mycobacterium tuberculosis infection leads to latent or active tuberculosis (TB). Increased uptake on 18F-fluoro-2-deoxy-glucose-positron emission tomography/computed tomography (FDG-PET/CT) has been reported in the lungs and lymph nodes of individuals with recent infection and active TB, but not in individuals without known recent exposure or suggestive symptoms. We describe five patients with lung nodules not suspected to be due to TB in whom abnormalities on FDG-PET/CT scans ultimately were attributed to TB infection.

RESULTS: Patient records were searched using the words "positron emission tomography/computed tomography" and 24 codes for TB between 2004 and 2013. Patients with a diagnosis of TB and a PET/CT scan were included. Clinical and radiographic data were retrieved. PET/CT images were reviewed by an experienced radiologist. FDG-PET/CT scans revealed elevated FDG-uptake in lungs of five patients subsequently diagnosed with active (n = 3) or clinically inactive (n = 2) tuberculosis. Uptake magnitude was unrelated to disease activity. These findings suggest that tuberculosis latency may include periods of percolating inflammation of uncertain relationship to future disease risk.}, } @article {pmid30001735, year = {2018}, author = {Bobo, FT and Woldie, M and Wordofa, MA and Tsega, G and Agago, TA and Wolde-Michael, K and Ibrahim, N and Yesuf, EA}, title = {Technical efficiency of public health centers in three districts in Ethiopia: two-stage data envelopment analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {465}, pmid = {30001735}, issn = {1756-0500}, mesh = {*Efficiency, Organizational ; Ethiopia ; Public Health ; *Public Health Administration ; }, abstract = {OBJECTIVE: The aim of the study was to measure technical and scale efficiency of public health centers in three districts of Jimma zone, Ethiopia. A two-stage data envelopment analysis was used. First, we estimated technical and scale efficiency of the health centers. In the second stage, institutional and environmental factors were against technical efficiency of the health centers to identify factors associated to efficiency of the health centers.

RESULTS: Eight out of the 16 health centers in the study were found to be technically efficient, with an average score of 90% (standard deviation = 17%). This indicates that on average they could have reduce their utilization of all inputs by about 10% without reducing output. On the other hand, 8 out of 16 health centers were found to be scale efficient, with an average scale efficiency score of 94% (standard deviation = 9%). The inefficient health centers had an average scale score of 89%; implying there is potential for increasing total outputs by about 11% using the existing capacity/size. Catchment population and number of clinical staff were found to be directly associated with efficiency, while the number of nonclinical staff was found to be inversely associated with efficiency.}, } @article {pmid30001706, year = {2018}, author = {Kosch, R and Delarocque, J and Claus, P and Becker, SC and Jung, K}, title = {Gene expression profiles in neurological tissues during West Nile virus infection: a critical meta-analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {530}, pmid = {30001706}, issn = {1471-2164}, support = {N-RENNT//Ministry of Science and Culture of Lower Saxony, Germany/ ; }, mesh = {Animals ; Databases, Genetic ; Immune System/metabolism/virology ; Neurons/*metabolism/virology ; Oligonucleotide Array Sequence Analysis ; Principal Component Analysis ; *Transcriptome ; West Nile Fever/pathology/veterinary/virology ; West Nile virus/pathogenicity ; }, abstract = {BACKGROUND: Infections with the West Nile virus (WNV) can attack neurological tissues in the host and alter gene expression levels therein. Several individual studies have analyzed these changes in the transcriptome based on measurements with DNA microarrays. Individual microarray studies produce a high-dimensional data structure with the number of studied genes exceeding the available sample size by far. Therefore, the level of scientific evidence of these studies is rather low and results can remain uncertain. Furthermore, the individual studies concentrate on different types of tissues or different time points after infection. A general statement regarding the transcriptional changes through WNV infection in neurological tissues is therefore hard to make. We screened public databases for transcriptome expression studies related to WNV infections and used different analysis pipelines to perform meta-analyses of these data with the goal of obtaining more stable results and increasing the level of evidence.

RESULTS: We generated new lists of genes differentially expressed between WNV infected neurological tissues and control samples. A comparison with these genes to findings of a meta-analysis of immunological tissues is performed to figure out tissue-specific differences. While 5.879 genes were identified exclusively in the neurological tissues, 15 genes were found exclusively in the immunological tissues, and 44 genes were commonly detected in both tissues. Most findings of the original studies could be confirmed by the meta-analysis with a higher statistical power, but some genes and GO terms related to WNV were newly detected, too. In addition, we identified gene ontology terms related to certain infection processes, which are significantly enriched among the differentially expressed genes. In the neurological tissues, 17 gene ontology terms were found significantly different, and 2 terms in the immunological tissues.

CONCLUSIONS: A critical discussion of our findings shows benefits but also limitations of the meta-analytic approach. In summary, the produced gene lists, identified gene ontology terms and network reconstructions appear to be more reliable than the results from the individual studies. Our meta-analysis provides a basis for further research on the transcriptional mechanisms by WNV infections in neurological tissues.}, } @article {pmid30001702, year = {2018}, author = {Shao, H and Ganesamoorthy, D and Duarte, T and Cao, MD and Hoggart, CJ and Coin, LJM}, title = {npInv: accurate detection and genotyping of inversions using long read sub-alignment.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {261}, pmid = {30001702}, issn = {1471-2105}, abstract = {BACKGROUND: Detection of genomic inversions remains challenging. Many existing methods primarily target inzversions with a non repetitive breakpoint, leaving inverted repeat (IR) mediated non-allelic homologous recombination (NAHR) inversions largely unexplored.

RESULT: We present npInv, a novel tool specifically for detecting and genotyping NAHR inversion using long read sub-alignment of long read sequencing data. We benchmark npInv with other tools in both simulation and real data. We use npInv to generate a whole-genome inversion map for NA12878 consisting of 30 NAHR inversions (of which 15 are novel), including all previously known NAHR mediated inversions in NA12878 with flanking IR less than 7kb. Our genotyping accuracy on this dataset was 94%. We used PCR to confirm the presence of two of these novel inversions. We show that there is a near linear relationship between the length of flanking IR and the minimum inversion size, without inverted repeats.

CONCLUSION: The application of npInv shows high accuracy in both simulation and real data. The results give deeper insight into understanding inversion.}, } @article {pmid30001700, year = {2018}, author = {Fu, Y and Wu, PH and Beane, T and Zamore, PD and Weng, Z}, title = {Elimination of PCR duplicates in RNA-seq and small RNA-seq using unique molecular identifiers.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {531}, pmid = {30001700}, issn = {1471-2164}, support = {P01 HD078253/HD/NICHD NIH HHS/United States ; R37 GM062862/GM/NIGMS NIH HHS/United States ; R37GM062862//National Institute of General Medical Sciences/ ; HD078253//Eunice Kennedy Shriver National Institute of Child Health and Human Development/ ; }, mesh = {Animals ; Gene Library ; Male ; Mice ; Polymerase Chain Reaction ; RNA/chemistry/*isolation & purification/metabolism ; Reproducibility of Results ; Sequence Analysis, RNA/*methods ; Testis/metabolism ; }, abstract = {BACKGROUND: RNA-seq and small RNA-seq are powerful, quantitative tools to study gene regulation and function. Common high-throughput sequencing methods rely on polymerase chain reaction (PCR) to expand the starting material, but not every molecule amplifies equally, causing some to be overrepresented. Unique molecular identifiers (UMIs) can be used to distinguish undesirable PCR duplicates derived from a single molecule and identical but biologically meaningful reads from different molecules.

RESULTS: We have incorporated UMIs into RNA-seq and small RNA-seq protocols and developed tools to analyze the resulting data. Our UMIs contain stretches of random nucleotides whose lengths sufficiently capture diverse molecule species in both RNA-seq and small RNA-seq libraries generated from mouse testis. Our approach yields high-quality data while allowing unique tagging of all molecules in high-depth libraries.

CONCLUSIONS: Using simulated and real datasets, we demonstrate that our methods increase the reproducibility of RNA-seq and small RNA-seq data. Notably, we find that the amount of starting material and sequencing depth, but not the number of PCR cycles, determine PCR duplicate frequency. Finally, we show that computational removal of PCR duplicates based only on their mapping coordinates introduces substantial bias into data analysis.}, } @article {pmid30001697, year = {2018}, author = {Reitermayer, D and Kafka, TA and Lenz, CA and Vogel, RF}, title = {Interrelation between Tween and the membrane properties and high pressure tolerance of Lactobacillus plantarum.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {72}, pmid = {30001697}, issn = {1471-2180}, abstract = {Tween® 80 is a frequently used supplement of media for the cultivation of lactic acid bacteria. We investigated its effect on the cell physiology and stress tolerance of Lactobacillus (L.) plantarum. Data on the transcriptomic response to Tween 80 supplementation and its effects on cellular fatty acid profiles and growth characteristics are compared with data characterizing the effect of Tween 80, other Tween types and free fatty acids on the high hydrostatic pressure (HHP) tolerance of L. plantarum strain TMW 1.708. These include effects on cell viability, sub-lethal injury, metabolic activity, protein release and propidium iodide uptake. Tween 80 caused the downregulation of fatty acid biosynthesis and an increase in oleic acid and cyclopropane fatty acid levels in the cell membrane. Tween 20, Tween 80 and free oleic acid, but not Tween 40, Tween 60 and other free fatty acids, conferred resistance against HHP. Tween 80 diminished pressure-induced loss of metabolic activity, protein release and uptake of propidium iodide. However, loss of cell viability exceeded by far membrane permeabilization, suggesting that membrane permeabilization, which has frequently been postulated as a major factor in HHP inactivation of microbes, is not necessarily required for HHP-induced cell death of Lactobacillus plantarum.}, } @article {pmid30001694, year = {2018}, author = {Zhang, Y and Jenkins, DF and Manimaran, S and Johnson, WE}, title = {Alternative empirical Bayes models for adjusting for batch effects in genomic studies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {262}, pmid = {30001694}, issn = {1471-2105}, support = {R01 ES025002/ES/NIEHS NIH HHS/United States ; U01 CA164720/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Combining genomic data sets from multiple studies is advantageous to increase statistical power in studies where logistical considerations restrict sample size or require the sequential generation of data. However, significant technical heterogeneity is commonly observed across multiple batches of data that are generated from different processing or reagent batches, experimenters, protocols, or profiling platforms. These so-called batch effects often confound true biological relationships in the data, reducing the power benefits of combining multiple batches, and may even lead to spurious results in some combined studies. Therefore there is significant need for effective methods and software tools that account for batch effects in high-throughput genomic studies.

RESULTS: Here we contribute multiple methods and software tools for improved combination and analysis of data from multiple batches. In particular, we provide batch effect solutions for cases where the severity of the batch effects is not extreme, and for cases where one high-quality batch can serve as a reference, such as the training set in a biomarker study. We illustrate our approaches and software in both simulated and real data scenarios.

CONCLUSIONS: We demonstrate the value of these new contributions compared to currently established approaches in the specified batch correction situations.}, } @article {pmid30001693, year = {2018}, author = {Zhang, T and Zhang, SW and Zhang, L and Meng, J}, title = {trumpet: transcriptome-guided quality assessment of m6A-seq data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {260}, pmid = {30001693}, issn = {1471-2105}, abstract = {BACKGROUND: Methylated RNA immunoprecipitation sequencing (MeRIP-seq or m6A-seq) has been extensively used for profiling transcriptome-wide distribution of RNA N6-Methyl-Adnosine methylation. However, due to the intrinsic properties of RNA molecules and the intricate procedures of this technique, m6A-seq data often suffer from various flaws. A convenient and comprehensive tool is needed to assess the quality of m6A-seq data to ensure that they are suitable for subsequent analysis.

RESULTS: From a technical perspective, m6A-seq can be considered as a combination of ChIP-seq and RNA-seq; hence, by effectively combing the data quality assessment metrics of the two techniques, we developed the trumpet R package for evaluation of m6A-seq data quality. The trumpet package takes the aligned BAM files from m6A-seq data together with the transcriptome information as the inputs to generate a quality assessment report in the HTML format.

CONCLUSIONS: The trumpet R package makes a valuable tool for assessing the data quality of m6A-seq, and it is also applicable to other fragmented RNA immunoprecipitation sequencing techniques, including m1A-seq, CeU-Seq, Ψ-seq, etc.}, } @article {pmid30001201, year = {2018}, author = {Zhang, XY and Sukhchuluun, G and Bo, TB and Chi, QS and Yang, JJ and Chen, B and Zhang, L and Wang, DH}, title = {Correction to: Huddling remodels gut microbiota to reduce energy requirements in a small mammal species during cold exposure.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {126}, pmid = {30001201}, issn = {2049-2618}, abstract = {Following publication of the original article [1], the authors reported an error in the caption of Fig. 4.}, } @article {pmid30001200, year = {2018}, author = {Omari, S and Kamenir, Y and Benichou, JIC and Pariente, S and Sela, H and Perl-Treves, R}, title = {Correction to: Landraces of snake melon, an ancient Middle Eastern crop, reveal extensive morphological and DNA diversity for potential genetic improvement.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {44}, pmid = {30001200}, issn = {1471-2156}, abstract = {Following publication of the original article [1], the authors reported the need for a more detailed acknowledgement of the source of the samples that were analyzed and their coordinates, which are discussed in the 'Methods' section of the article. This Correction provides an addition to the 'Methods' section, and a subsequently revised 'Acknowledgements' and 'Availability of data and materials' section.}, } @article {pmid30001194, year = {2018}, author = {Forbes, AA and Bagley, RK and Beer, MA and Hippee, AC and Widmayer, HA}, title = {Quantifying the unquantifiable: why Hymenoptera, not Coleoptera, is the most speciose animal order.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {21}, pmid = {30001194}, issn = {1472-6785}, support = {1145355//Division of Environmental Biology/International ; 1542269//Division of Environmental Biology/International ; }, abstract = {BACKGROUND: We challenge the oft-repeated claim that the beetles (Coleoptera) are the most species-rich order of animals. Instead, we assert that another order of insects, the Hymenoptera, is more speciose, due in large part to the massively diverse but relatively poorly known parasitoid wasps. The idea that the beetles have more species than other orders is primarily based on their respective collection histories and the relative availability of taxonomic resources, which both disfavor parasitoid wasps. Though it is unreasonable to directly compare numbers of described species in each order, the ecology of parasitic wasps-specifically, their intimate interactions with their hosts-allows for estimation of relative richness.

RESULTS: We present a simple logical model that shows how the specialization of many parasitic wasps on their hosts suggests few scenarios in which there would be more beetle species than parasitic wasp species. We couple this model with an accounting of what we call the "genus-specific parasitoid-host ratio" from four well-studied genera of insect hosts, a metric by which to generate extremely conservative estimates of the average number of parasitic wasp species attacking a given beetle or other insect host species.

CONCLUSIONS: Synthesis of our model with data from real host systems suggests that the Hymenoptera may have 2.5-3.2× more species than the Coleoptera. While there are more described species of beetles than all other animals, the Hymenoptera are almost certainly the larger order.}, } @article {pmid29998561, year = {2018}, author = {Parins-Fukuchi, C}, title = {Bayesian placement of fossils on phylogenies using quantitative morphometric data.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1801-1814}, doi = {10.1111/evo.13516}, pmid = {29998561}, issn = {1558-5646}, abstract = {Jointly developing a comprehensive tree of life from living and fossil taxa has long been a fundamental goal in evolutionary biology. One major challenge has stemmed from difficulties in merging evidence from extant and extinct organisms. While these efforts have resulted in varying stages of synthesis, they have been hindered by their dependence on qualitative descriptions of morphology. Though rarely applied to phylogenetic inference, traditional and geometric morphometric data can improve these issues by generating more rigorous ways to quantify variation in morphological structures. They may also facilitate the rapid and objective aggregation of large morphological datasets. I describe a new Bayesian method that leverages quantitative trait data to reconstruct the positions of fossil taxa on fixed reference trees composed of extant taxa. Unlike most formulations of phylogenetic Brownian motion models, this method expresses branch lengths in units of morphological disparity, suggesting a new framework through which to construct Bayesian node calibration priors for molecular dating and explore comparative patterns in morphological disparity. I am hopeful that the approach described here will help to facilitate a deeper integration of neo- and paleontological data to move morphological phylogenetics further into the genomic era.}, } @article {pmid29998528, year = {2018}, author = {Phen, A and Greer, J and Uppal, J and Der, J and Boughner, JC}, title = {Upper jaw development in the absence of teeth: New insights for craniodental evo-devo integration.}, journal = {Evolution & development}, volume = {20}, number = {5}, pages = {146-159}, doi = {10.1111/ede.12261}, pmid = {29998528}, issn = {1525-142X}, support = {2011-402148//Natural Sciences and Engineering Research Council of Canada/International ; 2016-05177//Natural Sciences and Engineering Research Council of Canada/International ; //NSERC Undergraduate Summer Research Awards/International ; #29037//Canada Foundation for Innovation/International ; //Leaders Opportunity Fund/International ; //College of Medicine, University of Saskatchewan/International ; //Biomedical Research Summer Student Awards/International ; }, mesh = {Animals ; *Biological Evolution ; Craniofacial Abnormalities/*genetics ; Embryo, Mammalian/anatomy & histology/metabolism ; Maxilla/anatomy & histology/*embryology ; Mice ; Mice, Inbred C57BL ; Odontogenesis ; Phosphoproteins/genetics/metabolism ; Tooth/pathology ; Trans-Activators/genetics/metabolism ; }, abstract = {In p63-null mice (p63-/-), teeth fail to form but the mandible forms normally; conversely, the upper jaw skeleton is malformed. Here we explored whether lack of dental tissues contributed to midfacial dysmorphologies in p63-/- mice by testing if facial prominence defects appeared before odontogenesis failed. We also investigated gene dose effects by testing if one wild type (WT) p63 allele (p63+/-) was sufficient for normal upper jaw skeleton formation. We micro-CT scanned PFA-fixed p63-/- , p63+/- , and WT (p63+/+) adult and embryonic mice aged E10-E14. Next, we landmarked mandibular (MdP), maxillary (MxP) and nasal prominences (NPs), and facial bones. 3D landmark data were assessed using Principal Component, Canonical Variate, Partial Least Squares, and other statistical analyses. The p63-/- embryos showed MxP and NP malformations by E12, despite the presence of dental tissues. MdP shape was comparable among p63-/- , p63+/- , and p63+/+ embryos. Upper jaw shape was comparable between p63+/+ and p63+/- adults. The upper jaw and its dentition both require p63 signaling, but not each other's presence, to form properly. One WT p63 allele enables normal midfacial morphogenesis; gene dose may be a target for jaw macroevolution. Jaw-specific genetic mechanisms likely integrate the evo-devo of dentitions with upper versus lower jaws.}, } @article {pmid29998472, year = {2018}, author = {Harrison, MC and Arning, N and Kremer, LPM and Ylla, G and Belles, X and Bornberg-Bauer, E and Huylmans, AK and Jongepier, E and Piulachs, MD and Richards, S and Schal, C}, title = {Expansions of key protein families in the German cockroach highlight the molecular basis of its remarkable success as a global indoor pest.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {5}, pages = {254-264}, doi = {10.1002/jez.b.22824}, pmid = {29998472}, issn = {1552-5015}, abstract = {The German cockroach, Blattella germanica, is a worldwide pest that infests buildings, including homes, restaurants, and hospitals, often living in unsanitary conditions. As a disease vector and producer of allergens, this species has major health and economic impacts on humans. Factors contributing to the success of the German cockroach include its resistance to a broad range of insecticides, immunity to many pathogens, and its ability, as an extreme generalist omnivore, to survive on most food sources. The recently published genome shows that B. germanica has an exceptionally high number of protein coding genes. In this study, we investigate the functions of the 93 significantly expanded gene families with the aim to better understand the success of B. germanica as a major pest despite such inhospitable conditions. We find major expansions in gene families with functions related to the detoxification of insecticides and allelochemicals, defense against pathogens, digestion, sensory perception, and gene regulation. These expansions might have allowed B. germanica to develop multiple resistance mechanisms to insecticides and pathogens, and enabled a broad, flexible diet, thus explaining its success in unsanitary conditions and under recurrent chemical control. The findings and resources presented here provide insights for better understanding molecular mechanisms that will facilitate more effective cockroach control.}, } @article {pmid29998471, year = {2018}, author = {Minorsky, PV}, title = {The functions of foliar nyctinasty: a review and hypothesis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12444}, pmid = {29998471}, issn = {1469-185X}, abstract = {Foliar nyctinasty is a plant behaviour characterised by a pronounced daily oscillation in leaf orientation. During the day, the blades of nyctinastic plant leaves (or leaflets) assume a more or less horizontal position that optimises their ability to capture sunlight for photosynthesis. At night, the positions that the leaf blades assume, regardless of whether they arise by rising, falling or twisting, are essentially vertical. Among the ideas put forth to explain the raison d'être of foliar nyctinasty are that it: (i) improves the temperature relations of plants; (ii) helps remove surface water from foliage; (iii) prevents the disruption of photoperiodism by moonlight; and (iv) directly discourages insect herbivory. After discussing these previous hypotheses, a novel tritrophic hypothesis is introduced that proposes that foliar nyctinasty constitutes an indirect plant defence against nocturnal herbivores. It is suggested that the reduction in physical clutter that follows from nocturnal leaf closure may increase the foraging success of many types of animals that prey upon or parasitise herbivores. Predators and parasitoids generally use some combination of visual, auditory or olfactory cues to detect prey. In terrestrial environments, it is hypothesised that the vertical orientation of the blades of nyctinastic plants at night would be especially beneficial to flying nocturnal predators (e.g. bats and owls) and parasitoids whose modus operandi is death from above. The movements of prey beneath a plant with vertically oriented foliage would be visually more obvious to gleaning or swooping predators under nocturnal or crepuscular conditions. Such predators could also detect sounds made by prey better without baffling layers of foliage overhead to damp and disperse the signal. Moreover, any volatiles released by the prey would diffuse more directly to the awaiting olfactory apparatus of the predators or parasitoids. In addition to facilitating the demise of herbivores by carnivores and parasitoids, foliar nyctinasty, much like the enhanced illumination of the full moon, may mitigate feeding by nocturnal herbivores by altering their foraging behaviour. Foliar nyctinasty could also provide a competitive advantage by encouraging herbivores, seeking more cover, to forage on or around non-nyctinastic species. As an added advantage, foliar nyctinasty, by decreasing the temperature between plants through its effects on re-radiation, may slow certain types of ectothermic herbivores making them more vulnerable to predation. Foliar nyctinasty also may not solely be a behavioural adaptation against folivores; by discouraging foraging by granivores, the inclusive fitness of nyctinastic plants may be increased.}, } @article {pmid29997742, year = {2018}, author = {Liu, H and Liu, X and Li, J}, title = {Correction to: Complete genome of a novel virulent phage ST0 lysing Escherichia coli H8.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {15}, doi = {10.1186/s40793-018-0319-x}, pmid = {29997742}, issn = {1944-3277}, abstract = {[This corrects the article DOI: 10.1186/s40793-017-0304-9.].}, } @article {pmid29997696, year = {2018}, author = {Ota, MOC and Kirigia, DG and Asamoah-Odei, E and Drameh-Avognon, PS and Olu, O and Malecela, MN and Cabore, JW and Moeti, MR}, title = {Proceedings of the first African Health Forum: effective partnerships and intersectoral collaborations are critical for attainment of Universal Health Coverage in Africa.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 7}, pages = {8}, pmid = {29997696}, issn = {1753-6561}, abstract = {Background: Universal Health Coverage (UHC)is central to the health Sustainable Development Goals(SDG). Working towards UHC is a powerful mechanism for achieving the right to health and promoting human development which is a priority area of focus for the World Health Organization WHO. As a result, the WHO Regional Office for Africa convened the first-ever Africa Health Forum, co- hosted by the government of Rwanda in Kigali in June 2017 with the theme "Putting People First: The Road to Universal Health Coverage in Africa". The Forum aimed to strengthen and forge new partnerships, align priorities and galvanize commitment to advance the health agenda in Africa in order to attain UHC and the SDGs. This paper reports the proceedings and conclusions of the forum.

Methods: The forum was attended by over 800 participants. It employed moderated panel and public discussions, and side events with political leaders, policy makers and technicians from ministries of health and finance, United Nations agencies, the private sector, the academia, philanthropic foundations, youth, women and non-governmental organizations drawn from within and outside the Region.

Conclusions: The commitment to achieve UHC was a collective expression of the belief that all people should have access to the health services they need without risk of financial hardship. The attainment of UHC will require a significant paradigm shift, including development of new partnerships especially public-private partnerships in selected areas with limited government resources, intersectoral collaboration to engage in interventions that affect health but are outside the purview of the ministries in charge of health and identification of public health issues where knowledge gaps exist as research priorities. The deliberations of the Forum culminated into a "Call-to-Action" - Putting People First: The Road to Universal Health Coverage in Africa, which pledged a renewed determination for Member States, in partnership with the private Sector, WHO, other UN Agencies and partners to support the attainment of the SDGs and UHC. There was agreement that immediate action was required to implement the call-to-action, and that the African Regional Office of WHO should develop a plan to rapidly operationalize the outcomes of the meeting.}, } @article {pmid29997176, year = {2018}, author = {Sharma, S and Čermáková, K and De Rijck, J and Demeulemeester, J and Fábry, M and El Ashkar, S and Van Belle, S and Lepšík, M and Tesina, P and Duchoslav, V and Novák, P and Hubálek, M and Srb, P and Christ, F and Řezáčová, P and Hodges, HC and Debyser, Z and Veverka, V}, title = {Affinity switching of the LEDGF/p75 IBD interactome is governed by kinase-dependent phosphorylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7053-E7062}, pmid = {29997176}, issn = {1091-6490}, support = {R00 CA187565/CA/NCI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Amino Acid Motifs ; Cell Line, Tumor ; HIV/enzymology/genetics ; HIV Integrase/genetics/metabolism ; Histone-Lysine N-Methyltransferase/genetics/metabolism ; Humans ; Mediator Complex Subunit 1/genetics/metabolism ; Myeloid-Lymphoid Leukemia Protein/genetics/metabolism ; Phosphorylation/genetics ; Transcription Factors/genetics/*metabolism ; }, abstract = {Lens epithelium-derived growth factor/p75 (LEDGF/p75, or PSIP1) is a transcriptional coactivator that tethers other proteins to gene bodies. The chromatin tethering function of LEDGF/p75 is hijacked by HIV integrase to ensure viral integration at sites of active transcription. LEDGF/p75 is also important for the development of mixed-lineage leukemia (MLL), where it tethers the MLL1 fusion complex at aberrant MLL targets, inducing malignant transformation. However, little is known about how the LEDGF/p75 protein interaction network is regulated. Here, we obtained solution structures of the complete interfaces between the LEDGF/p75 integrase binding domain (IBD) and its cellular binding partners and validated another binding partner, Mediator subunit 1 (MED1). We reveal that structurally conserved IBD-binding motifs (IBMs) on known LEDGF/p75 binding partners can be regulated by phosphorylation, permitting switching between low- and high-affinity states. Finally, we show that elimination of IBM phosphorylation sites on MLL1 disrupts the oncogenic potential of primary MLL1-rearranged leukemic cells. Our results demonstrate that kinase-dependent phosphorylation of MLL1 represents a previously unknown oncogenic dependency that may be harnessed in the treatment of MLL-rearranged leukemia.}, } @article {pmid29997175, year = {2018}, author = {Wang, Y and Zaytsev, ME and Lajoinie, G and The, HL and Eijkel, JCT and van den Berg, A and Versluis, M and Weckhuysen, BM and Zhang, X and Zandvliet, HJW and Lohse, D}, title = {Giant and explosive plasmonic bubbles by delayed nucleation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7676-7681}, pmid = {29997175}, issn = {1091-6490}, abstract = {When illuminated by a laser, plasmonic nanoparticles immersed in water can very quickly and strongly heat up, leading to the nucleation of so-called plasmonic vapor bubbles. While the long-time behavior of such bubbles has been well-studied, here, using ultrahigh-speed imaging, we reveal the nucleation and early life phase of these bubbles. After some delay time from the beginning of the illumination, a giant bubble explosively grows, and collapses again within 200 μs (bubble life phase 1). The maximal bubble volume [Formula: see text] remarkably increases with decreasing laser power, leading to less total dumped energy E. This dumped energy shows a universal linear scaling relation with [Formula: see text], irrespective of the gas concentration of the surrounding water. This finding supports that the initial giant bubble is a pure vapor bubble. In contrast, the delay time does depend on the gas concentration of the water, as gas pockets in the water facilitate an earlier vapor bubble nucleation, which leads to smaller delay times and lower bubble nucleation temperatures. After the collapse of the initial giant bubbles, first, much smaller oscillating bubbles form out of the remaining gas nuclei (bubble life phase 2). Subsequently, the known vaporization dominated growth phase takes over, and the bubble stabilizes (life phase 3). In the final life phase 4, the bubble slowly grows by gas expelling due to heating of the surrounding. Our findings on the explosive growth and collapse during the early life phase of a plasmonic vapor bubble have strong bearings on possible applications of such bubbles.}, } @article {pmid29997174, year = {2018}, author = {Striem-Amit, E and Vannuscorps, G and Caramazza, A}, title = {Plasticity based on compensatory effector use in the association but not primary sensorimotor cortex of people born without hands.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7801-7806}, pmid = {29997174}, issn = {1091-6490}, mesh = {Female ; Humans ; Male ; *Neuronal Plasticity ; Sensorimotor Cortex/*physiopathology ; Upper Extremity Deformities, Congenital/*physiopathology ; }, abstract = {What forces direct brain organization and its plasticity? When brain regions are deprived of their input, which regions reorganize based on compensation for the disability and experience, and which regions show topographically constrained plasticity? People born without hands activate their primary sensorimotor hand region while moving body parts used to compensate for this disability (e.g., their feet). This was taken to suggest a neural organization based on functions, such as performing manual-like dexterous actions, rather than on body parts, in primary sensorimotor cortex. We tested the selectivity for the compensatory body parts in the primary and association sensorimotor cortex of people born without hands (dysplasic individuals). Despite clear compensatory foot use, the primary sensorimotor hand area in the dysplasic subjects showed preference for adjacent body parts that are not compensatorily used as effectors. This suggests that function-based organization, proposed for congenital blindness and deafness, does not apply to the primary sensorimotor cortex deprivation in dysplasia. These findings stress the roles of neuroanatomical constraints like topographical proximity and connectivity in determining the functional development of primary cortex even in extreme, congenital deprivation. In contrast, increased and selective foot movement preference was found in dysplasics' association cortex in the inferior parietal lobule. This suggests that the typical motor selectivity of this region for manual actions may correspond to high-level action representations that are effector-invariant. These findings reveal limitations to compensatory plasticity and experience in modifying brain organization of early topographical cortex compared with association cortices driven by function-based organization.}, } @article {pmid29997173, year = {2018}, author = {Bandala-Sanchez, E and G Bediaga, N and Goddard-Borger, ED and Ngui, K and Naselli, G and Stone, NL and Neale, AM and Pearce, LA and Wardak, A and Czabotar, P and Haselhorst, T and Maggioni, A and Hartley-Tassell, LA and Adams, TE and Harrison, LC}, title = {CD52 glycan binds the proinflammatory B box of HMGB1 to engage the Siglec-10 receptor and suppress human T cell function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7783-7788}, pmid = {29997173}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Antibodies/pharmacology ; CD52 Antigen/*immunology ; Female ; HMGB1 Protein/antagonists & inhibitors/*immunology ; Humans ; Lectins/*immunology ; Male ; Protein Domains ; Protein Tyrosine Phosphatase, Non-Receptor Type 6/immunology ; Receptors, Antigen, T-Cell/*immunology ; T-Lymphocytes/*immunology ; }, abstract = {CD52, a glycophosphatidylinositol (GPI)-anchored glycoprotein, is released in a soluble form following T cell activation and binds to the Siglec (sialic acid-binding Ig-like lectin)-10 receptor on T cells to suppress their function. We show that binding of CD52-Fc to Siglec-10 and T cell suppression requires the damage-associated molecular pattern (DAMP) protein, high-mobility group box 1 (HMGB1). CD52-Fc bound specifically to the proinflammatory Box B domain of HMGB1, and this in turn promoted binding of the CD52 N-linked glycan, in α-2,3 sialic acid linkage with galactose, to Siglec-10. Suppression of T cell function was blocked by anti-HMGB1 antibody or the antiinflammatory Box A domain of HMGB1. CD52-Fc induced tyrosine phosphorylation of Siglec-10 and was recovered from T cells complexed with HMGB1 and Siglec-10 in association with SHP1 phosphatase and the T cell receptor (TCR). Thus, soluble CD52 exerts a concerted immunosuppressive effect by first sequestering HMGB1 to nullify its proinflammatory Box B, followed by binding to the inhibitory Siglec-10 receptor, triggering recruitment of SHP1 to the intracellular immunoreceptor tyrosine-based inhibitory motif of Siglec-10 and its interaction with the TCR. This mechanism may contribute to immune-inflammatory homeostasis in pathophysiologic states and underscores the potential of soluble CD52 as a therapeutic agent.}, } @article {pmid29997172, year = {2018}, author = {Liu, X and Shu, S and Korn, ED}, title = {Polymerization pathway of mammalian nonmuscle myosin 2s.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7101-E7108}, pmid = {29997172}, issn = {1091-6490}, mesh = {Animals ; Cytoskeleton/*chemistry/genetics/metabolism ; Humans ; Myosin Type II/*chemistry/genetics/metabolism ; Protein Domains ; *Protein Folding ; }, abstract = {The three mammalian nonmuscle myosin 2 (NM2) monomers, like all class 2 myosin monomers, are hexamers of two identical heavy (long) chains and two pairs of light (short) chains bound to the heavy chains. The heavy chains have an N-terminal globular motor domain (head) with actin-activated ATPase activity, a lever arm (neck) to which the two light chains bind, and a coiled-coil helical tail. Monomers polymerize into bipolar filaments, with globular heads at each end separated by a bare zone, by antiparallel association of their coiled-coil tails. NM2 filaments are highly dynamic in situ, frequently disassembling and reassembling at different locations within the cell where they are essential for multiple biological functions. Therefore, it is important to understand the mechanisms of filament polymerization and depolymerization. Monomers can exist in two states: folded and unfolded. It has been thought that unfolded monomers form antiparallel dimers that assemble into bipolar filaments. We now show that polymerization in vitro proceeds from folded monomers to folded antiparallel dimers to folded antiparallel tetramers that unfold forming antiparallel bipolar tetramers. Folded dimers and tetramers then associate with the unfolded tetramer and unfold, forming a mature bipolar filament consisting of multiple unfolded tetramers with an entwined bare zone. We also demonstrate that depolymerization is essentially the reverse of the polymerization process. These results will advance our understanding of NM2 filament dynamics in situ.}, } @article {pmid29996947, year = {2018}, author = {Shahab, H and Khan, HS and Almas, A and Tufail, M and Kazmi, KA and Khan, AH}, title = {The Post Clinic Ambulatory Blood Pressure (PC-ABP) study correlates Post Clinic Blood Pressure (PCBP) with the gold standard Ambulatory Blood Pressure.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {460}, pmid = {29996947}, issn = {1756-0500}, support = {80096//Faculty of Health Sciences, Seed Money Commitee, Aga Khan University (PK)/ ; }, mesh = {Adolescent ; Adult ; *Blood Pressure ; Blood Pressure Determination ; *Blood Pressure Monitoring, Ambulatory ; Cross-Sectional Studies ; Female ; Humans ; Hypertension/*diagnosis ; Male ; Pakistan ; }, abstract = {OBJECTIVE: Our previous study showed that post-clinic blood pressure (BP) taken 15 min after a physician-patient encounter was the lowest reading in a routine clinic. We aimed to validate this reading with 24 h Ambulatory Blood Pressure Monitoring (ABPM) readings. A cross-sectional study was conducted in the cardiology clinics at the Aga Khan University, Pakistan. Hypertensive patients aged ≥ 18 years, or those referred for the diagnosis of hypertension were included.

RESULTS: Of 150 participants, 49% were males. 76% of all participants were hypertensive. Pre-clinic BP reading was measured by a nurse, in-clinic by a physician and 15 min post-clinic by a research assistant using a validated, automated BP device (Omron-HEM7221-E). All patients were referred for 24 h ABPM. Among the three readings taken during a clinic visit, mean (± SD) systolic BP (SBP) pre-clinic, in-clinic, and 15 min post-clinic were 153.2 ± 23, 152.3 ± 21, and 140.0 ± 18 mmHg, respectively. Mean (± SD) diastolic BP (DBP) taken pre-clinic, in-clinic and 15 min post-clinic were 83.5 ± 12, 90.9 ± 12, and 86.4 ± 11 mmHg respectively. Mean (± SD) daytime ambulatory SBP, DBP and pulse readings were 134.7 ± 15, 78.7 ± 15 mmHg, and 72.6 ± 12/min, respectively. Pearson correlation coefficients of pre-clinic, in-clinic and post-clinic SBP with daytime ambulatory-SBP were 0.4 (p value: < 0.001), 0.5 (p value: < 0.001) and 0.6 (p value: < 0.001), respectively. Post-clinic BP has a good correlation with ambulatory BP and may be considered a more reliable reading in the clinic setting.}, } @article {pmid29996939, year = {2018}, author = {Stan, RC and Soriano, FG and de Camargo, MM}, title = {A mathematical model relates intracellular TLR4 oscillations to sepsis progression.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {462}, pmid = {29996939}, issn = {1756-0500}, support = {400662/2014-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 309041/2012-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 11/51778-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Disease Progression ; Gram-Negative Bacteria ; Humans ; Lipopolysaccharides ; *Models, Theoretical ; Sepsis/*physiopathology ; Signal Transduction ; Toll-Like Receptor 4/*metabolism ; }, abstract = {OBJECTIVE: Oscillations of physiological parameters describe many biological processes and their modulation is determinant for various pathologies. In sepsis, toll-like receptor 4 (TLR4) is a key sensor for signaling the presence of Gram-negative bacteria. Its intracellular trafficking rates shift the equilibrium between the pro- and anti-inflammatory downstream signaling cascades, leading to either the physiological resolution of the bacterial stimulation or to sepsis. This study aimed to evaluate the effects of TLR4 increased expression and intracellular trafficking on the course and outcome of sepsis.

RESULTS: Using a set of three differential equations, we defined the TLR4 fluxes between relevant cell organelles. We obtained three different regions in the phase space: (1) a limit-cycle describing unstimulated physiological oscillations, (2) a fixed-point attractor resulting from moderate LPS stimulation that is resolved and (3) a double-attractor resulting from sustained LPS stimulation that leads to sepsis. We used this model to describe available hospital data of sepsis patients and we correctly characterize the clinical outcome of these patients.}, } @article {pmid29996927, year = {2018}, author = {Agbor, VN and Tagny, CT and Kenmegne, JB and Awazi, B and Ngansop, C and Mbanya, D and Ndembi, N}, title = {Prevalence of anti-hepatitis C antibodies and its co-infection with HIV in rural Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {459}, pmid = {29996927}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Cameroon ; Child ; *Coinfection ; Female ; HIV Antibodies ; HIV Infections/*complications ; Hepatitis B ; Hepatitis C/*complications ; Hepatitis C Antibodies/*blood ; Humans ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the prevalence of the co-infection between the human immunodeficiency virus (HIV) and hepatitis C virus (HCV), and the prevalence of factors associated with HCV transmission in a rural Cameroonian community.

RESULTS: The mean age of the 174 participants included in the study was 30.3 (standard deviation = 13.26) years (age range 12-77 years). the prevalence of HCV/HIV co-infection was 1.7% [95% confidence interval (CI) 1.1-5.9]. The prevalence of HCV and HIV were 6.3% (95% CI 2.9-10.3) and 6.9 (95% CI 5.2-11.3), respectively. Histories of scarification (62.1%), multiple sex partners (31.0%) and sexually transmitted diseases (66.1%) were the most common risk factors of HCV transmission in this study.}, } @article {pmid29996923, year = {2018}, author = {González-Pech, PG and Torres-Acosta, JFJ and Sandoval-Castro, CA}, title = {Simpler intake estimation using direct observation in small ruminants: grouping bites by plant structure and morphology.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {453}, pmid = {29996923}, issn = {1756-0500}, support = {290662//CONACYT-MEXICO/ ; CB-2008-01/106146//CONACYT-MEXICO/ ; }, mesh = {Animal Feed ; Animals ; *Diet ; Eating ; Goats ; Mexico ; *Plant Structures ; Poaceae ; *Ruminants ; Sheep ; }, abstract = {OBJECTIVE: To validate the estimation of dry matter intake (DMI) obtained from bite categories (BC) and weight for every plant species (method 1: M1) vs. an alternative method (method 2: M2) grouping plants based on structure and leaf morphology. A dataset containing 80,813 bites and 33 plant species obtained by M1 for sheep and goats browsing a tropical forest was used. Plant species and their respective bite weight were regrouped according to M2. BC weights within each morphological group were compared using ANOVA and post hoc Tukey's honest significant difference comparisons. DMI was estimated for sheep, goats and DMI obtained with both approaches was compared using the t-test, Pearson correlation and orthogonal regression analyses.

RESULTS: Dry matter intake estimations were: M1 = 369 ± 153 vs. M2 = 425 ± 161 gDM for sheep and M1 = 567 ± 190 vs. M2 = 681 ± 203 gDM for goats. DMI estimations by M1 and M2 were similar and strongly correlated. Orthogonal regression showed both procedures yielded a similar DMI estimation (P < 0.001). M2 reduces the amount of work required to estimate DMI in heterogeneous vegetation without reducing accuracy. M2 reduced the time required and made simpler to include data from larger number of animals/replicates.}, } @article {pmid29996918, year = {2018}, author = {Hashmi, AA and Faraz, M and Nauman, Z and Qureshi, MU and Hashmi, SK and Waseem, HF and Edhi, MM and Faridi, N and Khan, A}, title = {Clinicopathologic features and prognostic grouping of gastrointestinal stromal tumors (GISTs) in Pakistani patients: an institutional perspective.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {457}, pmid = {29996918}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Female ; Gastrointestinal Neoplasms/*diagnosis/pathology/therapy ; Gastrointestinal Stromal Tumors/*diagnosis/pathology/therapy ; Humans ; Male ; Middle Aged ; Pakistan ; Prognosis ; Stomach Neoplasms ; Young Adult ; }, abstract = {OBJECTIVES: Gastrointestinal stromal tumors (GISTs) are rare tumors of gastrointestinal tract, prognosis of which largely depends upon histopathologic characteristics of resection specimens, which were not widely studied in our population. Therefore we aimed to evaluate the histopathologic characteristics of GISTs in our population and their prognostic grouping according to college of American pathologist's guidelines.

RESULTS: Mean age of patients was 53.4 years (18-71 years). 92% of cases were of primary GISTs and stomach was the most common site (57.7%). 75% of cases were of spindle cell morphology and 53.8% belonged to high risk prognostic group. Comparison of stomach and intestinal GISTs showed that intestinal GISTs were found to be of high grade (70%) and of high risk prognostic group (75 and 80%) compared to stomach GISTs (43% were of high risk prognostic group), however this finding was not statistically significant. GISTs are infrequent gastrointestinal tumors but early diagnosis and identification of adverse histological features are key to successful treatment. We found a large majority of GISTs to be located in stomach, however intestinal GISTs were found more likely to be associated with adverse prognostic parameters. However more large scale studies are warranted to establish this finding.}, } @article {pmid29996913, year = {2018}, author = {Senra, C and Gomes, LI and Siqueira, LMV and Coelho, PMZ and Rabello, A and Oliveira, E}, title = {Development of a laboratorial platform for diagnosis of schistosomiasis mansoni by PCR-ELISA.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {455}, pmid = {29996913}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Animals ; Brazil ; *Enzyme-Linked Immunosorbent Assay ; Feces/parasitology ; Female ; Humans ; Male ; Mice ; Middle Aged ; Parasite Egg Count ; *Polymerase Chain Reaction ; Prevalence ; Schistosoma mansoni ; Schistosomiasis mansoni/*diagnosis ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVE: We developed a laboratorial platform to release a commercial platform used in the PCR-ELISA for the molecular diagnosis of schistosomiasis mansoni. On following, PCR-ELISA platform laboratorial was evaluated in 206 feces samples collected of individual living in a Brazilian low endemicity area.

RESULTS: The PCR-ELISA laboratorial platform indicated a prevalence rate of 25.2%, which was higher than the Kato-Katz technique (18.4%) and lower than the commercial platform (30.1%). Considering Kato-Katz technique as the reference, there were 97.4% and 91.1% of relative sensitivity and specificity rates, respectively. The laboratorial platform presented good precision, performance diagnostic, and can be used in replacement to the commercial platform for diagnosis of schistosomiasis by PCR-ELISA.}, } @article {pmid29996909, year = {2018}, author = {Herrmann, A and Sanson-Fisher, R and Hall, A and Wall, L and Zdenkowski, N and Waller, A}, title = {Support persons' preferences for the type of consultation and the format of information provided when making a cancer treatment decision.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {456}, pmid = {29996909}, issn = {1756-0500}, support = {APP1059760//National Health and Medical Research Council/ ; CSR 11-02//Cancer Council NSW/ ; Research scholarship//Faculty of Health and Medicine, University of Newcastle Australia/ ; Research scholarship//Hunter Cancer Reseaerch Alliance/ ; RHD student award//Hunter Cancer Reseaerch Alliance/ ; Early Career Research Award//Australian Research Council Discovery/ ; }, mesh = {Adult ; Cross-Sectional Studies ; *Decision Making ; Female ; Humans ; Male ; Medical Oncology ; Middle Aged ; Neoplasms/*therapy ; *Patient Participation ; Patient Preference ; Physician-Patient Relations ; *Referral and Consultation ; }, abstract = {OBJECTIVE: Cancer patients and their support persons commonly feel overwhelmed when being confronted with their diagnosis and treatment options. We used a DCE to examine patients' and support persons' preferences for: (i) attending one 40 min consultation or two 20 min consultations when making a cancer treatment decision; and for (ii) receiving additional information in written form only or in both written and online forms. Here we focus on support persons' preferences and whether they differ from patients' preferences.

RESULTS: 159 adult medical oncology patients and 64 of their support persons took part in this study. Participants were presented with a set of hypothetical scenarios and asked to indicate their most and least preferred scenario. 92% of support persons (n = 59) completed the DCE. Most preferred to receive two consultations along with written and online information (n = 30, 51%). This was the only scenario that was chosen by statistically significantly more support persons (p =0.037). The proportions of patients and support persons choosing each scenario did not differ significantly from each other (p >0.05). Our findings suggest that when making cancer treatment decisions, clinicians should consider offering patients and support persons written and online information, combined with two shorter consultations.}, } @article {pmid29996907, year = {2018}, author = {Cariou, M and Ribière, C and Morlière, S and Gauthier, JP and Simon, JC and Peyret, P and Charlat, S}, title = {Comparing 16S rDNA amplicon sequencing and hybridization capture for pea aphid microbiota diversity analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {461}, pmid = {29996907}, issn = {1756-0500}, support = {CapSymbArt//Centre National de la Recherche Scientifique/ ; }, mesh = {Animals ; Aphids/*microbiology ; DNA, Ribosomal/*genetics ; High-Throughput Nucleotide Sequencing ; Microbiota/*genetics ; Peas ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; }, abstract = {OBJECTIVE: Targeted sequencing of 16S rDNA amplicons is routinely used for microbial community profiling but this method suffers several limitations such as bias affinity of universal primers and short read size. Gene capture by hybridization represents a promising alternative. Here we used a metagenomic extract from the pea aphid Acyrthosiphon pisum to compare the performances of two widely used PCR primer pairs with DNA capture, based on solution hybrid selection.

RESULTS: All methods produced an exhaustive description of the 8 bacterial taxa known to be present in this sample. In addition, the methods yielded similar quantitative results, with the number of reads strongly correlating with quantitative PCR controls. Both methods can thus be considered as qualitatively and quantitatively robust on such a sample with low microbial complexity.}, } @article {pmid29996898, year = {2018}, author = {Agbozo, EY and Dumashie, E and Boakye, DA and de Souza, DK}, title = {Effects of lyophilization and storage temperature on Wuchereria bancrofti antigen sensitivity and stability.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {454}, pmid = {29996898}, issn = {1756-0500}, support = {98595//European and Developing Countries Clinical Trials Partnership/ ; }, mesh = {Animals ; Antigens, Helminth ; Elephantiasis, Filarial/*diagnosis ; *Freeze Drying ; Temperature ; Wuchereria bancrofti/*immunology ; }, abstract = {OBJECTIVE: Antigen-based rapid diagnostic tests for Lymphatic filariasis (LF) do not come with external quality control (QC) materials, and research and disease control programmes rely on stored positive samples. This study was undertaken to evaluate the use of lyophilized Wuchereria bancrofti antigen positive plasma samples to serve as QC materials for LF diagnostic tests. 10 well characterized W. bancrofti positive samples were lyophilized and stored at 4, 28 and 40 °C. The samples were evaluated using the Alere Filariasis Test Strips before lyophilization, and after 1 and 3 months of storage. The sensitivity and stability of the lyophilized samples were evaluated.

RESULTS: The results revealed a loss of sensitivity and stability with increasing temperature and duration of storage. The results are further discussed in terms of the use of dried blood spot (DBS) in diagnostic studies on LF, and the need for thoughtful DBS preparation and storage.}, } @article {pmid29996890, year = {2018}, author = {O'Reilly-Duff, H and Best, P and Tully, MA}, title = {Same old song and dance: an exploratory study of portrayal of physical activity in television programmes aimed at young adolescents.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {458}, pmid = {29996890}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; *Alcohol Drinking ; *Exercise ; Female ; Humans ; Life Style ; *Television ; }, abstract = {OBJECTIVE: Exposure to health-related behaviours on television has been shown to influence smoking and drinking in young people, but little research has been conducted on the portrayal physical activity. The aim of the current project was to explore the portrayal of physical activity in television programmes aimed specifically at adolescent females. Content analysis of 120 episodes of four popular adolescent television programmes was performed. Information on the type and context of physical activity, motivating factors and characters involved was recorded.

RESULTS: Physical activity was portrayed 122 times, for a duration of 1 h and 31 min (3.2% of total viewing time). Physical activity was mainly portrayed as part of an informal activity as part of a group activity. Over half (53.2%) of scenes portrayed activity been carried out by teenagers. The types of activities portrayed were mostly of vigorous intensity (76.2%), for recreational purposes (78.7%) such as dancing (54.1%) and running (11.5%), and motivated by enjoyment. This study highlights that physical activity is portrayed infrequently, and often with a skewed representation of type of activity. There may be an opportunity to influence physical activity in young adolescents through the positioning of positive images of an active lifestyle in the media.}, } @article {pmid29996828, year = {2018}, author = {Martínez-Lumbreras, S and Krysztofinska, EM and Thapaliya, A and Spilotros, A and Matak-Vinkovic, D and Salvadori, E and Roboti, P and Nyathi, Y and Muench, JH and Roessler, MM and Svergun, DI and High, S and Isaacson, RL}, title = {Structural complexity of the co-chaperone SGTA: a conserved C-terminal region is implicated in dimerization and substrate quality control.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {76}, pmid = {29996828}, issn = {1741-7007}, support = {BB/L006952/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; FC001029//Cancer Research UK/United Kingdom ; FC001029//Medical Research Council/United Kingdom ; FC001029//Wellcome Trust/United Kingdom ; G0900936//Medical Research Council/United Kingdom ; BB/L006510/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N006267/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 204957/Z/16/Z//Wellcome Trust/United Kingdom ; BB/J014567/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Protein quality control mechanisms are essential for cell health and involve delivery of proteins to specific cellular compartments for recycling or degradation. In particular, stray hydrophobic proteins are captured in the aqueous cytosol by a co-chaperone, the small glutamine-rich, tetratricopeptide repeat-containing protein alpha (SGTA), which facilitates the correct targeting of tail-anchored membrane proteins, as well as the sorting of membrane and secretory proteins that mislocalize to the cytosol and endoplasmic reticulum-associated degradation. Full-length SGTA has an unusual elongated dimeric structure that has, until now, evaded detailed structural analysis. The C-terminal region of SGTA plays a key role in binding a broad range of hydrophobic substrates, yet in contrast to the well-characterized N-terminal and TPR domains, there is a lack of structural information on the C-terminal domain. In this study, we present new insights into the conformation and organization of distinct domains of SGTA and show that the C-terminal domain possesses a conserved region essential for substrate processing in vivo.

RESULTS: We show that the C-terminal domain region is characterized by α-helical propensity and an intrinsic ability to dimerize independently of the N-terminal domain. Based on the properties of different regions of SGTA that are revealed using cell biology, NMR, SAXS, Native MS, and EPR, we observe that its C-terminal domain can dimerize in the full-length protein and propose that this reflects a closed conformation of the substrate-binding domain.

CONCLUSION: Our results provide novel insights into the structural complexity of SGTA and provide a new basis for mechanistic studies of substrate binding and release at the C-terminal region.}, } @article {pmid29996827, year = {2018}, author = {Roychoudhury, P and De Silva Feelixge, H and Reeves, D and Mayer, BT and Stone, D and Schiffer, JT and Jerome, KR}, title = {Viral diversity is an obligate consideration in CRISPR/Cas9 designs for targeting the HIV reservoir.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {75}, pmid = {29996827}, issn = {1741-7007}, support = {UM1 AI126623//National Institute of Allergy and Infectious Diseases/International ; P30 AI 027757-28//National Institute of Allergy and Infectious Diseases/International ; }, abstract = {BACKGROUND: RNA-guided CRISPR/Cas9 systems can be designed to mutate or excise the integrated HIV genome from latently infected cells and have therefore been proposed as a curative approach for HIV. However, most studies to date have focused on molecular clones with ideal target site recognition and do not account for target site variability observed within and between patients. For clinical success and broad applicability, guide RNA (gRNA) selection must account for circulating strain diversity and incorporate the within-host diversity of HIV.

RESULTS: We identified a set of gRNAs targeting HIV LTR, gag, and pol using publicly available sequences for these genes and ranked gRNAs according to global conservation across HIV-1 group M and within subtypes A-C. By considering paired and triplet combinations of gRNAs, we found triplet sets of target sites such that at least one of the gRNAs in the set was present in over 98% of all globally available sequences. We then selected 59 gRNAs from our list of highly conserved LTR target sites and evaluated in vitro activity using a loss-of-function LTR-GFP fusion reporter. We achieved efficient GFP knockdown with multiple gRNAs and found clustering of highly active gRNA target sites near the middle of the LTR. Using published deep-sequence data from HIV-infected patients, we found that globally conserved sites also had greater within-host target conservation. Lastly, we developed a mathematical model based on varying distributions of within-host HIV sequence diversity and enzyme efficacy. We used the model to estimate the number of doses required to deplete the latent reservoir and achieve functional cure thresholds. Our modeling results highlight the importance of within-host target site conservation. While increased doses may overcome low target cleavage efficiency, inadequate targeting of rare strains is predicted to lead to rebound upon cART cessation even with many doses.

CONCLUSIONS: Target site selection must account for global and within host viral genetic diversity. Globally conserved target sites are good starting points for design, but multiplexing is essential for depleting quasispecies and preventing viral load rebound upon therapy cessation.}, } @article {pmid29996787, year = {2018}, author = {Ke, M and Gao, Z and Chen, J and Qiu, Y and Zhang, L and Chen, X}, title = {Auxin controls circadian flower opening and closure in the waterlily.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {143}, pmid = {29996787}, issn = {1471-2229}, support = {2017YFA0506100//National Key Research and Development Program of China/ ; }, abstract = {BACKGROUND: Flowers open at sunrise and close at sunset, establishing a circadian floral movement rhythm to facilitate pollination as part of reproduction. By the coordination of endogenous factors and environmental stimuli, such as circadian clock, photoperiod, light and temperature, an appropriate floral movement rhythm has been established; however, the underlying mechanisms remain unclear.

RESULTS: In our study, we use waterlily as a model which represents an early-diverging grade of flowering plants, and we aim to reveal the general mechanism of flower actions. We found that the intermediate segment of petal cells of waterlily are highly flexible, followed by a circadian cell expansion upon photoperiod stimuli. Auxin causes constitutively flower opening while auxin inhibitor suppresses opening event. Subsequent transcriptome profiles generated from waterlily's intermediate segment of petals at different day-time points showed that auxin is a crucial phytohormone required for floral movement rhythm via the coordination of YUCCA-controlled auxin synthesis, GH3-mediated auxin homeostasis, PIN and ABCB-dependent auxin efflux as well as TIR/AFB-AUX/IAA- and SAUR-triggered auxin signaling. Genes involved in cell wall organization were downstream of auxin events, resulting in the output phenotypes of rapid cell expansion during flower opening and cell shrinkage at flower closure stage.

CONCLUSIONS: Collectively, our data demonstrate a central regulatory role of auxin in floral movement rhythm and provide a global understanding of flower action in waterlily, which could be a conserved feature of angiosperms.}, } @article {pmid29996779, year = {2018}, author = {Greer, JB and Schmale, MC and Fieber, LA}, title = {Whole-transcriptome changes in gene expression accompany aging of sensory neurons in Aplysia californica.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {529}, pmid = {29996779}, issn = {1471-2164}, support = {P40 OD010952//National Institutes of Health/ ; }, mesh = {Aging/*genetics ; Animals ; Aplysia/*genetics/metabolism ; Down-Regulation ; Gene Ontology ; Ion Channels/genetics/metabolism ; Principal Component Analysis ; RNA/chemistry/isolation & purification/metabolism ; Sensory Receptor Cells/*metabolism ; Sequence Analysis, RNA ; Signal Transduction/genetics ; *Transcriptome ; Up-Regulation ; }, abstract = {BACKGROUND: Large-scale molecular changes occur during aging and have many downstream consequences on whole-organism function, such as motor function, learning, and memory. The marine mollusk Aplysia californica can be used to study transcriptional changes that occur with age in identified neurons of the brain, because its simplified nervous system allows for more direct correlations between molecular changes, physiological changes, and their phenotypic outcomes. Behavioral deficits in the tail-withdrawal reflex of aged animals have been correlated with reduced excitation in sensory neurons that control the reflex. RNASeq was used to investigate whole-transcriptome changes in tail-withdrawal sensory neurons of sexually mature and aged Aplysia to correlate transcriptional changes with reduced behavioral and physiological responses.

RESULTS: Paired-end sequencing resulted in 210 million reads used for differential expression analysis. Aging significantly altered expression of 1202 transcripts in sensory neurons underlying the tail-withdrawal reflex, with an approximately equal number of these genes up- and down regulated with age. Despite overall bidirectionality of expression changes, > 80% of ion channel genes that were differentially expressed had decreased expression with age. In particular, several voltage-gated K+ and Ca2+ channels were down regulated. This marked decrease in ion channel expression may play an important role in previously observed declines in aged sensory neuron excitability. We also observed decreased expression of genes and pathways involved in learning and memory. Genes involved in the stress response showed increased expression in aged Aplysia neurons.

CONCLUSIONS: Significantly altered expression of many genes between sexually mature and aged Aplysia suggests large molecular changes that may impact neuronal function. Decreased ion channel mRNA observed could mean fewer receptors present in aged neurons, resulting in reduced excitability of PVC sensory neurons, ultimately leading to reduced tail-withdrawal reflex observed in aged Aplysia. Significant changes in other genes and pathways, such as stress response and learning and memory, have previously been shown to occur with age in many vertebrate organisms. This suggests that some effects of aging are common across many animal phyla.}, } @article {pmid29996775, year = {2018}, author = {Plesnar-Bielak, A and Skwierzyńska, AM and Hlebowicz, K and Radwan, J}, title = {Relative costs and benefits of alternative reproductive phenotypes at different temperatures - genotype-by-environment interactions in a sexually selected trait.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {109}, pmid = {29996775}, issn = {1471-2148}, support = {UMO-2015/19/B/NZ8/01393//Narodowe Centrum Nauki/International ; }, mesh = {Animals ; *Biological Evolution ; Female ; *Gene-Environment Interaction ; Genetic Variation ; Genotype ; Longevity/genetics ; Male ; Mites/*genetics ; Phenotype ; Polymorphism, Genetic ; *Quantitative Trait, Heritable ; Reproduction/*genetics ; Sexual Behavior, Animal/*physiology ; *Temperature ; Time Factors ; }, abstract = {BACKGROUND: The maintenance of considerable genetic variation in sexually selected traits (SSTs) is puzzling given directional selection expected to act on these traits. A possible explanation is the existence of a genotype-by-environment (GxE) interaction for fitness, by which elaborate SSTs are favored in some environments but selected against in others. In the current study, we look for such interactions for fitness-related traits in the bulb mite, a male-dimorphic species with discontinuous expression of a heritable SST in the form of enlarged legs that are used as weapons.

RESULTS: We show that evolution at 18 °C resulted in populations with a higher prevalence of this SST compared to evolution at 24 °C. We further demonstrate that temperature modified male reproductive success in a way that was consistent with these changes. There was a genotype-by-environment interaction for reproductive success - at 18 °C the relative reproductive success of armored males competing with unarmored ones was higher than at the moderate temperature of 24 °C. However, male morph did not have interactive effects with temperature with respect to other life history traits (development time and longevity).

CONCLUSIONS: A male genotype that is associated with the expression of a SST interacted with temperature in determining male reproductive success. This interaction caused an elaborate SST to evolve in different directions (more or less prevalent) depending on the thermal environment. The implication of this finding is that seasonal temperature fluctuations have the potential to maintain male polymorphism within populations. Furthermore, spatial heterogeneity in thermal conditions may cause differences among populations in SST selection. This could potentially cause selection against male immigrants from populations in different environments and thus strengthen barriers to gene flow.}, } @article {pmid29996774, year = {2018}, author = {Kajikawa, A and Suzuki, S and Igimi, S}, title = {The impact of motility on the localization of Lactobacillus agilis in the murine gastrointestinal tract.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {68}, pmid = {29996774}, issn = {1471-2180}, abstract = {BACKGROUND: While the overall composition of the mammalian gut microbiota has been intensively studied, the characteristics and ecologies of individual gut species are incompletely understood. Lactobacilli are considered beneficial commensals in the gastrointestinal mucosa and are relatively well-studied except for the uncommon species which exhibit motility. In this study, we evaluate the importance of motility on gut colonization by comparing motile and non-motile strains of Lactobacillus agilis in mice models.

RESULTS: A flagellated but non-motile L. agilis strain was constructed by mutation of the motB gene. Colonization of the wild type and the mutant strain was assessed in both antibiotic-treated female Balb/c mice and gnotobiotic mice. The results suggest that the motile strain is better able to persist and/or localize in the gut mucosa. Chemotaxis assays indicated that the motile L. agilis strain is attracted by mucin, which is a major component of the intestinal mucus layer in animal guts.

CONCLUSIONS: Motility and chemotactic ability likely confer advantages in gut colonization to L. agilis. These findings suggest that the motile lactobacilli have unique ecologies compared to non-motile commensals of the lactic acid bacteria.}, } @article {pmid29996771, year = {2018}, author = {Joesch-Cohen, LM and Robinson, M and Jabbari, N and Lausted, CG and Glusman, G}, title = {Novel metrics for quantifying bacterial genome composition skews.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {528}, pmid = {29996771}, issn = {1471-2164}, mesh = {Bacteria/*genetics ; Computational Biology/*methods ; *Genome, Bacterial ; Internet Access ; Models, Genetic ; User-Computer Interface ; }, abstract = {BACKGROUND: Bacterial genomes have characteristic compositional skews, which are differences in nucleotide frequency between the leading and lagging DNA strands across a segment of a genome. It is thought that these strand asymmetries arise as a result of mutational biases and selective constraints, particularly for energy efficiency. Analysis of compositional skews in a diverse set of bacteria provides a comparative context in which mutational and selective environmental constraints can be studied. These analyses typically require finished and well-annotated genomic sequences.

RESULTS: We present three novel metrics for examining genome composition skews; all three metrics can be computed for unfinished or partially-annotated genomes. The first two metrics, (dot-skew and cross-skew) depend on sequence and gene annotation of a single genome, while the third metric (residual skew) highlights unusual genomes by subtracting a GC content-based model of a library of genome sequences. We applied these metrics to 7738 available bacterial genomes, including partial drafts, and identified outlier species. A phylogenetically diverse set of these outliers (i.e., Borrelia, Ehrlichia, Kinetoplastibacterium, and Phytoplasma) display similar skew patterns but share lifestyle characteristics, such as intracellularity and biosynthetic dependence on their hosts.

CONCLUSIONS: Our novel metrics appear to reflect the effects of biosynthetic constraints and adaptations to life within one or more hosts on genome composition. We provide results for each analyzed genome, software and interactive visualizations at http://db.systemsbiology.net/gestalt/ skew_metrics .}, } @article {pmid29996769, year = {2018}, author = {He, Q and Hou, Q and Wang, Y and Li, J and Li, W and Kwok, LY and Sun, Z and Zhang, H and Zhong, Z}, title = {Comparative genomic analysis of Enterococcus faecalis: insights into their environmental adaptations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {527}, pmid = {29996769}, issn = {1471-2164}, support = {31601451//National Natural Science Foundations of China/ ; 31622043//National Natural Science Foundations of China/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Comparative Genomic Hybridization ; DNA, Bacterial/chemistry/isolation & purification/metabolism ; Drug Resistance, Bacterial/drug effects/genetics ; Enterococcus faecalis/classification/*genetics ; *Genome, Bacterial ; Phylogeny ; Sequence Analysis, DNA ; Virulence Factors/genetics ; }, abstract = {BACKGROUND: Enterococcus faecalis is widely studied as a common gut commensal and a nosocomial pathogen. In fact, Enterococcus faecalis is ubiquitous in nature, and it has been isolated from various niches, including the gastrointestinal tract, faeces, blood, urine, water, and fermented foods (such as dairy products). In order to elucidate the role of habitat in shaping the genome of Enterococcus faecalis, we performed a comparative genomic analysis of 78 strains of various origins.

RESULTS: Although no correlation was found between the strain isolation habitat and the phylogeny of Enterococcus faecalis from our whole genome-based phylogenetic analysis, our results revealed some environment-associated features in the analysed Enterococcus faecalis genomes. Significant differences were found in the genome size and the number of predicted open reading frames (ORFs) between strains originated from different environments. In general, strains from water sources had the smallest genome size and the least number of predicted ORFs. We also identified 293 environment-specific genes, some of which might link to the adaptive strategies for survival in particular environments. In addition, the number of antibiotic resistance genes was significantly different between strains isolated from dairy products, water, and blood. Strains isolated from blood had the largest number of antibiotic resistance genes.

CONCLUSION: These findings improve our understanding of the role of habitat in shaping the genomes of Enterococcus faecalis.}, } @article {pmid29996766, year = {2018}, author = {Kumari, G and Wong, KH and Serra, A and Shin, J and Yoon, HS and Sze, SK and Tam, JP}, title = {Molecular diversity and function of jasmintides from Jasminum sambac.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {144}, pmid = {29996766}, issn = {1471-2229}, support = {MOE2016-T3-1-003//AcRF Tier 3 funding/ ; }, abstract = {BACKGROUND: Jasmintides jS1 and jS2 from Jasminum sambac were previously identified as a novel family of cysteine-rich peptides (CRPs) with an unusual disulfide connectivity. However, very little else is known about jasmintides, particularly their molecular diversity and functions. Here, we report the discovery and characterization of a novel suite of jasmintides from J. sambac using transcriptomic, peptidomic, structural and functional tools.

RESULTS: Transcriptomic analysis of leaves, flowers and roots revealed 14 unique jasmintide precursors, all of which possess a three-domain architecture comprising a signal peptide, a pro-domain and a mature jasmintide domain. Peptidomic analysis, using fractionated mixtures of jasmintides and chemical derivatization of cysteine to pseudolysine, trypsin digestion and MS/MS sequencing, revealed an additional 86 jasmintides, some of which were post-translationally modified. NMR analysis showed that jasmintide jS3 has three anti-parallel β-strands with a three-disulfide connectivity of CysI-CysV, CysII-CysIV and CysIII-CysVI, which is similar to jasmintide jS1. Jasmintide jS3 was able to withstand thermal, acidic and enzymatic degradation and, importantly, exhibited antifeedant activity against mealworm Tenebrio molitor.

CONCLUSION: Together, this study expands the existing library of jasmintides and furthers our understanding of the molecular diversity and cystine framework of CRPs as scaffolds and tools for engineering peptides targeting pests.}, } @article {pmid29996765, year = {2018}, author = {Das, R and Romi, W and Das, R and Sharma, HK and Thakur, D}, title = {Antimicrobial potentiality of actinobacteria isolated from two microbiologically unexplored forest ecosystems of Northeast India.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {71}, pmid = {29996765}, issn = {1471-2180}, abstract = {BACKGROUND: Actinobacteria are often known to be great producers of antibiotics. The rapid increase in the global burden of antibiotic-resistance with the concurrent decline in the discovery of new antimicrobial molecules necessitates the search for novel and effective antimicrobial metabolites from unexplored ecological niches. The present study investigated the antimicrobial producing actinobacterial strains isolated from the soils of two microbiologically unexplored forest ecosystems, viz. Nameri National Park (NNP) and Panidehing Wildlife Sanctuary (PWS), located in the Eastern Himalayan Biodiversity hotspot region.

RESULTS: A total of 172 putative isolates of actinobacteria were isolated, of which 24 isolates showed strong antimicrobial bioactivity. Evaluation of the ethyl acetate extracts of culture supernatants against test microbial strains revealed that isolates PWS22, PWS41, PWS12, PWS52, PWS11, NNPR15, NNPR38, and NNPR69 were the potent producers of antimicrobial metabolites. The antimicrobial isolates dominantly belonged to Streptomyces, followed by Nocardia and Streptosporangium. Some of these isolates could be putative novel taxa. Analysis of the antimicrobial biosynthetic genes (type II polyketide synthase and nonribosomal peptide synthetase genes) showed that the antimicrobial metabolites were associated with pigment production and belonged to known families of bioactive secondary metabolites. Characterization of the antimicrobial metabolites of Streptomyces sp. PWS52, which showed lowest taxonomic identity among the studied potent antimicrobial metabolite producers, and their interaction with the test strains using GC-MS, UHPLC-MS, and scanning electron microscopy revealed that the potential bioactivity of PWS52 was due to the production of active antifungal and antibacterial metabolites like 2,5-bis(1,1-dimethylethyl) phenol, benzeneacetic acid and nalidixic acid.

CONCLUSIONS: Our findings suggest that the unexplored soil habitats of NNP and PWS forest ecosystems of Northeast India harbor previously undescribed actinobacteria with the capability to produce diverse antimicrobial metabolites that may be explored to overcome the rapidly rising global concern about antibiotic-resistance.}, } @article {pmid29996764, year = {2018}, author = {Velsko, IM and Shaddox, LM}, title = {Consistent and reproducible long-term in vitro growth of health and disease-associated oral subgingival biofilms.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {70}, pmid = {29996764}, issn = {1471-2180}, support = {R01DE019456/DE/NIDCR NIH HHS/United States ; T90 DE021990/DE/NIDCR NIH HHS/United States ; }, abstract = {BACKGROUND: Several in vitro oral biofilm growth systems can reliably construct oral microbiome communities in culture, yet their stability and reproducibility through time has not been well characterized. Long-term in vitro growth of natural biofilms would enable use of these biofilms in both in vitro and in vivo studies that require complex microbial communities with minimal variation over a period of time. Understanding biofilm community dynamics in continuous culture, and whether they maintain distinct signatures of health and disease, is necessary to determine the reliability and applicability of such models to broader studies. To this end, we performed next-generation sequencing on biofilms grown from healthy and disease-site subgingival plaque for 80 days to assess stability and reliability of continuous oral biofilm growth.

RESULTS: Biofilms were grown from subgingival plaque collected from periodontitis-affected sites and healthy individuals for ten eight-day long generations, using hydroxyapatite disks. The bacterial community in each generation was determined using Human Oral Microbe Identification by Next-Generation Sequencing (HOMINGS) technology, and analyzed in QIIME. Profiles were steady through the ten generations, as determined by species abundance and prevalence, Spearman's correlation coefficient, and Faith's phylogenetic distance, with slight variation predominantly in low abundance species. Community profiles were distinct between healthy and disease site-derived biofilms as demonstrated by weighted UniFrac distance throughout the ten generations. Differentially abundant species between healthy and disease site-derived biofilms were consistent throughout the generations.

CONCLUSIONS: Healthy and disease site-derived biofilms can reliably maintain consistent communities through ten generations of in vitro growth. These communities maintain signatures of health and disease and of individual donors despite culture in identical environments. This subgingival oral biofilm growth and perpetuation model may prove useful to studies involving oral infection or cell stimulation, or those measuring microbial interactions, which require the same biofilms over a period of time.}, } @article {pmid29996763, year = {2018}, author = {Aslam, ML and Carraro, R and Bestin, A and Cariou, S and Sonesson, AK and Bruant, JS and Haffray, P and Bargelloni, L and Meuwissen, THE}, title = {Genetics of resistance to photobacteriosis in gilthead sea bream (Sparus aurata) using 2b-RAD sequencing.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {43}, pmid = {29996763}, issn = {1471-2156}, support = {613611//European Union/ ; }, abstract = {BACKGROUND: Photobacteriosis is an infectious disease developed by a Gram-negative bacterium Photobacterium damselae subsp. piscicida (Phdp), which may cause high mortalities (90-100%) in sea bream. Selection and breeding for resistance against infectious diseases is a highly valuable tool to help prevent or diminish disease outbreaks, and currently available advanced selection methods with the application of genomic information could improve the response to selection. An experimental group of sea bream juveniles was derived from a Ferme Marine de Douhet (FMD, Oléron Island, France) selected line using ~ 109 parents (~ 25 females and 84 males). This group of 1187 individuals represented 177 full-sib families with 1-49 sibs per family, which were challenged with virulent Phdp for a duration of 18 days, and mortalities were recorded within this duration. Tissue samples were collected from the parents and the recorded offspring for DNA extraction, library preparation using 2b-RAD and genotyping by sequencing. Genotypic data was used to develop a linkage map, genome wide association analysis and for the estimation of breeding values.

RESULTS: The analysis of genetic variation for resistance against Phdp revealed moderate genomic heritability with estimates of ~ 0.32. A genome-wide association analysis revealed a quantitative trait locus (QTL) including 11 SNPs at linkage group 17 presenting significant association to the trait with p-value crossing genome-wide Bonferroni corrected threshold P ≤ 2.22e-06. The proportion total genetic variance explained by the single top most significant SNP was ranging from 13.28-16.14% depending on the method used to compute the variance. The accuracies of predicting breeding values obtained using genomic vs. pedigree information displayed 19-24% increase when using genomic information.

CONCLUSION: The current study demonstrates that SNPs-based genotyping of a sea bream population with 2b-RAD approach is effective at capturing the genetic variation for resistance against Phdp. Prediction accuracies obtained using genomic information were significantly higher than the accuracies obtained using pedigree information which highlights the importance and potential of genomic selection in commercial breeding programs.}, } @article {pmid29996759, year = {2018}, author = {Bi, Y and Zeng, S and Zhang, R and Diao, Q and Tu, Y}, title = {Effects of dietary energy levels on rumen bacterial community composition in Holstein heifers under the same forage to concentrate ratio condition.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {69}, pmid = {29996759}, issn = {1471-2180}, abstract = {BACKGROUND: The rumen bacterial community plays a critical role in feeds degradation and productivity. The effects of different forage to concentrate ratios on the ruminal microbial population structure have been studied extensively; however, research into changes in the ruminal bacterial community composition in heifers fed different energy level diets, with the same forage to concentrate ratio, has been very limited. The purpose of this study was to investigate the effects of different dietary energy levels, with the same forage to concentrate ratio, on ruminal bacterial community composition of heifers. Furthermore, we also determine the relationship between rumen bacteria and ruminal fermentation parameters.

RESULTS: The 16S rRNA gene sequencing showed that, under the same forage to concentrate ratio of 50:50, an 8% difference in dietary energy level had no significant impact on the alpha diversity and the relative abundance of the major phyla and most of the major genera in heifers. In all the treatments groups, Firmicutes, Bacteroidetes, and Proteobacteria were the dominant phyla. Spearman correlation analysis between the relative abundances of the rumen bacteria at the genus level and the fermentation parameters showed that the relative abundances of Prevotella and BF311 were positively correlated with the ammonia nitrogen and butyrate concentrations, and these two genera were negatively correlated with the propionate and isovalerate concentrations, respectively, and the genus Bifidobacterium was positively correlated with the butyrate concentration and was negatively correlated with propionate and isovalerate concentration. The total volatile fatty acid concentration was positively correlated with BF311 abundances, and was negatively correlated with Trichococcus and Facklamia abundances.

CONCLUSIONS: Under the same forage to concentrate ratio condition of 50:50, an 8% difference in dietary energy levels had little impact on rumen bacterial community composition in heifers. The correlations between some genera of ruminal bacteria and the concentrations of volatile fatty acids and ammonia nitrogen might be indicative that the ruminal fermentation parameters are strongly influenced by the rumen bacterial community composition.}, } @article {pmid29996063, year = {2019}, author = {Richardson, TL}, title = {Mechanisms and Pathways of Small-Phytoplankton Export from the Surface Ocean.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {57-74}, doi = {10.1146/annurev-marine-121916-063627}, pmid = {29996063}, issn = {1941-0611}, abstract = {Carbon fixation by phytoplankton near the surface and the sinking of this particulate material to deeper waters are key components of the biological carbon pump. The efficiency of the biological pump is influenced by the size and taxonomic composition of the phytoplankton community. Large, heavily ballasted taxa such as diatoms sink quickly and thus efficiently remove fixed carbon from the upper ocean. Smaller, nonballasted species such as picoplanktonic cyanobacteria are usually thought to contribute little to export production. Research in the past decade, however, has shed new light on the potential importance of small phytoplankton to carbon export, especially in oligotrophic oceans, where small cells dominate primary productivity. Here, I examine the mechanisms and pathways through which small-phytoplankton carbon is exported from the surface ocean and the role of small phytoplankton in food webs of a variety of ocean ecosystems.}, } @article {pmid29995870, year = {2018}, author = {}, title = {Meteorite fragment, deadly floods and French open-access push.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {156-157}, doi = {10.1038/d41586-018-05647-3}, pmid = {29995870}, issn = {1476-4687}, } @article {pmid29995869, year = {2018}, author = {Abbott, A}, title = {100 bats and a long, dark tunnel: one neuroscientist's quest to unlock the secrets of 3D navigation.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {165-168}, doi = {10.1038/d41586-018-05648-2}, pmid = {29995869}, issn = {1476-4687}, mesh = {Animal Migration/physiology ; Animals ; Brain/cytology/physiology ; Chiroptera/*physiology ; Decision Making ; Grid Cells/physiology ; Humans ; *Models, Animal ; Place Cells/physiology ; Spatial Navigation/*physiology ; }, } @article {pmid29995868, year = {2018}, author = {Van Noorden, R}, title = {Software beats animal tests at predicting toxicity of chemicals.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {163}, doi = {10.1038/d41586-018-05664-2}, pmid = {29995868}, issn = {1476-4687}, mesh = {Animals ; Machine Learning ; Reproducibility of Results ; *Software ; *Structure-Activity Relationship ; Toxicity Tests ; Toxicology ; }, } @article {pmid29995867, year = {2018}, author = {Zhou, KG and Vasu, KS and Cherian, CT and Neek-Amal, M and Zhang, JC and Ghorbanfekr-Kalashami, H and Huang, K and Marshall, OP and Kravets, VG and Abraham, J and Su, Y and Grigorenko, AN and Pratt, A and Geim, AK and Peeters, FM and Novoselov, KS and Nair, RR}, title = {Electrically controlled water permeation through graphene oxide membranes.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {236-240}, doi = {10.1038/s41586-018-0292-y}, pmid = {29995867}, issn = {1476-4687}, abstract = {Controlled transport of water molecules through membranes and capillaries is important in areas as diverse as water purification and healthcare technologies1-7. Previous attempts to control water permeation through membranes (mainly polymeric ones) have concentrated on modulating the structure of the membrane and the physicochemical properties of its surface by varying the pH, temperature or ionic strength3,8. Electrical control over water transport is an attractive alternative; however, theory and simulations9-14 have often yielded conflicting results, from freezing of water molecules to melting of ice14-16 under an applied electric field. Here we report electrically controlled water permeation through micrometre-thick graphene oxide membranes17-21. Such membranes have previously been shown to exhibit ultrafast permeation of water17,22 and molecular sieving properties18,21, with the potential for industrial-scale production. To achieve electrical control over water permeation, we create conductive filaments in the graphene oxide membranes via controllable electrical breakdown. The electric field that concentrates around these current-carrying filaments ionizes water molecules inside graphene capillaries within the graphene oxide membranes, which impedes water transport. We thus demonstrate precise control of water permeation, from ultrafast permeation to complete blocking. Our work opens up an avenue for developing smart membrane technologies for artificial biological systems, tissue engineering and filtration.}, } @article {pmid29995866, year = {2018}, author = {Puebla-Hellmann, G and Venkatesan, K and Mayor, M and Lörtscher, E}, title = {Metallic nanoparticle contacts for high-yield, ambient-stable molecular-monolayer devices.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {232-235}, doi = {10.1038/s41586-018-0275-z}, pmid = {29995866}, issn = {1476-4687}, abstract = {Accessing the intrinsic functionality of molecules for electronic applications1-3, light emission4 or sensing5 requires reliable electrical contacts to those molecules. A self-assembled monolayer (SAM) sandwich architecture6 is advantageous for technological applications, but requires a non-destructive, top-contact fabrication method. Various approaches ranging from direct metal evaporation6 over poly(3,4-ethylenedioxythiophene) polystyrene sulfonate7 (PEDOT:PSS) or graphene8 interlayers to metal transfer printing9 have been proposed. Nevertheless, it has not yet been possible to fabricate SAM-based devices without compromising film integrity, intrinsic functionality or mass-fabrication compatibility. Here we develop a top-contact approach to SAM-based devices that simultaneously addresses all these issues, by exploiting the fact that a metallic nanoparticle can provide a reliable electrical contact to individual molecules10. Our fabrication route involves first the conformal and non-destructive deposition of a layer of metallic nanoparticles directly onto the SAM (itself laterally constrained within circular pores in a dielectric matrix, with diameters ranging from 60 nanometres to 70 micrometres), and then the reinforcement of this top contact by direct metal evaporation. This approach enables the fabrication of thousands of identical, ambient-stable metal-molecule-metal devices. Systematic variation of the composition of the SAM demonstrates that the intrinsic molecular properties are not affected by the nanoparticle layer and subsequent top metallization. Our concept is generic to densely packed layers of molecules equipped with two anchor groups, and provides a route to the large-scale integration of molecular compounds into solid-state devices that can be scaled down to the single-molecule level.}, } @article {pmid29995865, year = {2018}, author = {Bryan, BA and Gao, L and Ye, Y and Sun, X and Connor, JD and Crossman, ND and Stafford-Smith, M and Wu, J and He, C and Yu, D and Liu, Z and Li, A and Huang, Q and Ren, H and Deng, X and Zheng, H and Niu, J and Han, G and Hou, X}, title = {China's response to a national land-system sustainability emergency.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {193-204}, doi = {10.1038/s41586-018-0280-2}, pmid = {29995865}, issn = {1476-4687}, mesh = {Agriculture ; Biodiversity ; China ; Conservation of Natural Resources ; Food Supply ; Forests ; Goals ; Grassland ; *Soil ; Sustainable Development/economics/legislation & jurisprudence/*trends ; Time Factors ; United Nations ; Water ; }, abstract = {China has responded to a national land-system sustainability emergency via an integrated portfolio of large-scale programmes. Here we review 16 sustainability programmes, which invested US$378.5 billion (in 2015 US$), covered 623.9 million hectares of land and involved over 500 million people, mostly since 1998. We find overwhelmingly that the interventions improved the sustainability of China's rural land systems, but the impacts are nuanced and adverse outcomes have occurred. We identify some key characteristics of programme success, potential risks to their durability, and future research needs. We suggest directions for China and other nations as they progress towards the Sustainable Development Goals of the United Nations' Agenda 2030.}, } @article {pmid29995864, year = {2018}, author = {Graham, NAJ and Wilson, SK and Carr, P and Hoey, AS and Jennings, S and MacNeil, MA}, title = {Seabirds enhance coral reef productivity and functioning in the absence of invasive rats.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {250-253}, doi = {10.1038/s41586-018-0202-3}, pmid = {29995864}, issn = {1476-4687}, mesh = {Animals ; Anthozoa/*physiology ; Aquatic Organisms/metabolism ; Biomass ; Birds/*physiology ; Charadriiformes/physiology ; *Coral Reefs ; Data Analysis ; Fishes/metabolism ; *Food Chain ; Herbivory ; Indian Ocean ; *Introduced Species ; Islands ; Nitrogen/metabolism ; Porifera/metabolism ; Rats ; Seaweed/metabolism ; }, abstract = {Biotic connectivity between ecosystems can provide major transport of organic matter and nutrients, influencing ecosystem structure and productivity1, yet the implications are poorly understood owing to human disruptions of natural flows2. When abundant, seabirds feeding in the open ocean transport large quantities of nutrients onto islands, enhancing the productivity of island fauna and flora3,4. Whether leaching of these nutrients back into the sea influences the productivity, structure and functioning of adjacent coral reef ecosystems is not known. Here we address this question using a rare natural experiment in the Chagos Archipelago, in which some islands are rat-infested and others are rat-free. We found that seabird densities and nitrogen deposition rates are 760 and 251 times higher, respectively, on islands where humans have not introduced rats. Consequently, rat-free islands had substantially higher nitrogen stable isotope (δ15N) values in soils and shrubs, reflecting pelagic nutrient sources. These higher values of δ15N were also apparent in macroalgae, filter-feeding sponges, turf algae and fish on adjacent coral reefs. Herbivorous damselfish on reefs adjacent to the rat-free islands grew faster, and fish communities had higher biomass across trophic feeding groups, with 48% greater overall biomass. Rates of two critical ecosystem functions, grazing and bioerosion, were 3.2 and 3.8 times higher, respectively, adjacent to rat-free islands. Collectively, these results reveal how rat introductions disrupt nutrient flows among pelagic, island and coral reef ecosystems. Thus, rat eradication on oceanic islands should be a high conservation priority as it is likely to benefit terrestrial ecosystems and enhance coral reef productivity and functioning by restoring seabird-derived nutrient subsidies from large areas of ocean.}, } @article {pmid29995863, year = {2018}, author = {Kasahara, Y and Ohnishi, T and Mizukami, Y and Tanaka, O and Ma, S and Sugii, K and Kurita, N and Tanaka, H and Nasu, J and Motome, Y and Shibauchi, T and Matsuda, Y}, title = {Majorana quantization and half-integer thermal quantum Hall effect in a Kitaev spin liquid.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {227-231}, doi = {10.1038/s41586-018-0274-0}, pmid = {29995863}, issn = {1476-4687}, abstract = {The quantum Hall effect in two-dimensional electron gases involves the flow of topologically protected dissipationless charge currents along the edges of a sample. Integer or fractional electrical conductance is associated with edge currents of electrons or quasiparticles with fractional charges, respectively. It has been predicted that quantum Hall phenomena can also be created by edge currents with a fundamentally different origin: the fractionalization of quantum spins. However, such quantization has not yet been observed. Here we report the observation of this type of quantization of the Hall effect in an insulating two-dimensional quantum magnet1, α-RuCl3, with a dominant Kitaev interaction (a bond-dependent Ising-type interaction) on a two-dimensional honeycomb lattice2-7. We find that the application of a magnetic field parallel to the sample destroys long-range magnetic order, leading to a field-induced quantum-spin-liquid ground state with substantial entanglement of local spins8-12. In the low-temperature regime of this state, the two-dimensional thermal Hall conductance reaches a quantum plateau as a function of the applied magnetic field and has a quantization value that is exactly half of the two-dimensional thermal Hall conductance of the integer quantum Hall effect. This half-integer quantization of the thermal Hall conductance in a bulk material is a signature of topologically protected chiral edge currents of charge-neutral Majorana fermions (particles that are their own antiparticles), which have half the degrees of freedom of conventional fermions13-16. These results demonstrate the fractionalization of spins into itinerant Majorana fermions and Z2 fluxes, which is predicted to occur in Kitaev quantum spin liquids1,3. Above a critical magnetic field, the quantization disappears and the thermal Hall conductance goes to zero rapidly, indicating a topological quantum phase transition between the states with and without chiral Majorana edge modes. Emergent Majorana fermions in a quantum magnet are expected to have a great impact on strongly correlated quantum matter, opening up the possibility of topological quantum computing at relatively high temperatures.}, } @article {pmid29995862, year = {2018}, author = {Maier, E and Zhang, X and Abelmann, A and Gersonde, R and Mulitza, S and Werner, M and Méheust, M and Ren, J and Chapligin, B and Meyer, H and Stein, R and Tiedemann, R and Lohmann, G}, title = {North Pacific freshwater events linked to changes in glacial ocean circulation.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {241-245}, doi = {10.1038/s41586-018-0276-y}, pmid = {29995862}, issn = {1476-4687}, mesh = {Diatoms/chemistry ; Foraminifera/chemistry ; *Freezing ; Fresh Water/*analysis ; *Ice Cover ; Oxygen Isotopes/analysis ; Pacific Ocean ; Salinity ; Seawater/*analysis ; Temperature ; *Water Movements ; }, abstract = {There is compelling evidence that episodic deposition of large volumes of freshwater into the oceans strongly influenced global ocean circulation and climate variability during glacial periods1,2. In the North Atlantic region, episodes of massive freshwater discharge to the North Atlantic Ocean were related to distinct cold periods known as Heinrich Stadials1-3. By contrast, the freshwater history of the North Pacific region remains unclear, giving rise to persistent debates about the existence and possible magnitude of climate links between the North Pacific and North Atlantic oceans during Heinrich Stadials4,5. Here we find that there was a strong connection between changes in North Atlantic circulation during Heinrich Stadials and injections of freshwater from the North American Cordilleran Ice Sheet to the northeastern North Pacific. Our record of diatom δ18O (a measure of the ratio of the stable oxygen isotopes 18O and 16O) over the past 50,000 years shows a decrease in surface seawater δ18O of two to three per thousand, corresponding to a decline in salinity of roughly two to four practical salinity units. This coincided with enhanced deposition of ice-rafted debris and a slight cooling of the sea surface in the northeastern North Pacific during Heinrich Stadials 1 and 4, but not during Heinrich Stadial 3. Furthermore, results from our isotope-enabled model6 suggest that warming of the eastern Equatorial Pacific during Heinrich Stadials was crucial for transmitting the North Atlantic signal to the northeastern North Pacific, where the associated subsurface warming resulted in a discernible freshwater discharge from the Cordilleran Ice Sheet during Heinrich Stadials 1 and 4. However, enhanced background cooling across the northern high latitudes during Heinrich Stadial 3-the coldest period in the past 50,000 years7-prevented subsurface warming of the northeastern North Pacific and thus increased freshwater discharge from the Cordilleran Ice Sheet. In combination, our results show that nonlinear ocean-atmosphere background interactions played a complex role in the dynamics linking the freshwater discharge responses of the North Atlantic and North Pacific during glacial periods.}, } @article {pmid29995861, year = {2018}, author = {Roth, TL and Puig-Saus, C and Yu, R and Shifrut, E and Carnevale, J and Li, PJ and Hiatt, J and Saco, J and Krystofinski, P and Li, H and Tobin, V and Nguyen, DN and Lee, MR and Putnam, AL and Ferris, AL and Chen, JW and Schickel, JN and Pellerin, L and Carmody, D and Alkorta-Aranburu, G and Del Gaudio, D and Matsumoto, H and Morell, M and Mao, Y and Cho, M and Quadros, RM and Gurumurthy, CB and Smith, B and Haugwitz, M and Hughes, SH and Weissman, JS and Schumann, K and Esensten, JH and May, AP and Ashworth, A and Kupfer, GM and Greeley, SAW and Bacchetta, R and Meffre, E and Roncarolo, MG and Romberg, N and Herold, KC and Ribas, A and Leonetti, MD and Marson, A}, title = {Reprogramming human T cell function and specificity with non-viral genome targeting.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {405-409}, pmid = {29995861}, issn = {1476-4687}, support = {DP3 DK111914/DK/NIDDK NIH HHS/United States ; T32 DK007418/DK/NIDDK NIH HHS/United States ; T32 GM007618/GM/NIGMS NIH HHS/United States ; R35 CA197633/CA/NCI NIH HHS/United States ; P50 GM082250/GM/NIGMS NIH HHS/United States ; K23 DK094866/DK/NIDDK NIH HHS/United States ; K23 AI115001/AI/NIAID NIH HHS/United States ; P30 DK020595/DK/NIDDK NIH HHS/United States ; }, abstract = {Decades of work have aimed to genetically reprogram T cells for therapeutic purposes1,2 using recombinant viral vectors, which do not target transgenes to specific genomic sites3,4. The need for viral vectors has slowed down research and clinical use as their manufacturing and testing is lengthy and expensive. Genome editing brought the promise of specific and efficient insertion of large transgenes into target cells using homology-directed repair5,6. Here we developed a CRISPR-Cas9 genome-targeting system that does not require viral vectors, allowing rapid and efficient insertion of large DNA sequences (greater than one kilobase) at specific sites in the genomes of primary human T cells, while preserving cell viability and function. This permits individual or multiplexed modification of endogenous genes. First, we applied this strategy to correct a pathogenic IL2RA mutation in cells from patients with monogenic autoimmune disease, and demonstrate improved signalling function. Second, we replaced the endogenous T cell receptor (TCR) locus with a new TCR that redirected T cells to a cancer antigen. The resulting TCR-engineered T cells specifically recognized tumour antigens and mounted productive anti-tumour cell responses in vitro and in vivo. Together, these studies provide preclinical evidence that non-viral genome targeting can enable rapid and flexible experimental manipulation and therapeutic engineering of primary human immune cells.}, } @article {pmid29995860, year = {2018}, author = {Seeholzer, LF and Seppo, M and Stern, DL and Ruta, V}, title = {Evolution of a central neural circuit underlies Drosophila mate preferences.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {564-569}, pmid = {29995860}, issn = {1476-4687}, support = {DP2 NS087942/NS/NINDS NIH HHS/United States ; DP2 NS0879422013/NH/NIH HHS/United States ; }, mesh = {Alkadienes/metabolism ; Animals ; *Biological Evolution ; Courtship ; Drosophila Proteins/metabolism ; Drosophila melanogaster/classification/*physiology ; Drosophila simulans/classification/*physiology ; Female ; Ion Channels/metabolism ; Male ; Mating Preference, Animal/*physiology ; Nerve Tissue Proteins/metabolism ; *Neural Pathways ; *Reproductive Isolation ; Sensory Receptor Cells/metabolism ; Sex Attractants/metabolism ; Species Specificity ; Transcription Factors/metabolism ; }, abstract = {Courtship rituals serve to reinforce reproductive barriers between closely related species. Drosophila melanogaster and Drosophila simulans exhibit reproductive isolation, owing in part to the fact that D. melanogaster females produce 7,11-heptacosadiene, a pheromone that promotes courtship in D. melanogaster males but suppresses courtship in D. simulans males. Here we compare pheromone-processing pathways in D. melanogaster and D. simulans males to define how these sister species endow 7,11-heptacosadiene with the opposite behavioural valence to underlie species discrimination. We show that males of both species detect 7,11-heptacosadiene using homologous peripheral sensory neurons, but this signal is differentially propagated to P1 neurons, which control courtship behaviour. A change in the balance of excitation and inhibition onto courtship-promoting neurons transforms an excitatory pheromonal cue in D. melanogaster into an inhibitory cue in D. simulans. Our results reveal how species-specific pheromone responses can emerge from conservation of peripheral detection mechanisms and diversification of central circuitry, and demonstrate how flexible nodes in neural circuits can contribute to behavioural evolution.}, } @article {pmid29995859, year = {2018}, author = {Yan, Y and Liu, Q and Zang, X and Yuan, S and Bat-Erdene, U and Nguyen, C and Gan, J and Zhou, J and Jacobsen, SE and Tang, Y}, title = {Resistance-gene-directed discovery of a natural-product herbicide with a new mode of action.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {415-418}, pmid = {29995859}, issn = {1476-4687}, support = {DP1 GM106413/GM/NIGMS NIH HHS/United States ; R35 GM118056/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Bioactive natural products have evolved to inhibit specific cellular targets and have served as lead molecules for health and agricultural applications for the past century1-3. The post-genomics era has brought a renaissance in the discovery of natural products using synthetic-biology tools4-6. However, compared to traditional bioactivity-guided approaches, genome mining of natural products with specific and potent biological activities remains challenging4. Here we present the discovery and validation of a potent herbicide that targets a critical metabolic enzyme that is required for plant survival. Our approach is based on the co-clustering of a self-resistance gene in the natural-product biosynthesis gene cluster7-9, which provides insight into the potential biological activity of the encoded compound. We targeted dihydroxy-acid dehydratase in the branched-chain amino acid biosynthetic pathway in plants; the last step in this pathway is often targeted for herbicide development10. We show that the fungal sesquiterpenoid aspterric acid, which was discovered using the method described above, is a sub-micromolar inhibitor of dihydroxy-acid dehydratase that is effective as a herbicide in spray applications. The self-resistance gene astD was validated to be insensitive to aspterric acid and was deployed as a transgene in the establishment of plants that are resistant to aspterric acid. This herbicide-resistance gene combination complements the urgent ongoing efforts to overcome weed resistance11. Our discovery demonstrates the potential of using a resistance-gene-directed approach in the discovery of bioactive natural products.}, } @article {pmid29995858, year = {2018}, author = {Balesdent, J and Basile-Doelsch, I and Chadoeuf, J and Cornu, S and Derrien, D and Fekiacova, Z and Hatté, C}, title = {Atmosphere-soil carbon transfer as a function of soil depth.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {599-602}, doi = {10.1038/s41586-018-0328-3}, pmid = {29995858}, issn = {1476-4687}, mesh = {Agriculture ; Atmosphere/*chemistry ; Biomass ; Carbon/*analysis/metabolism ; Carbon Isotopes/analysis/metabolism ; Climate ; Crops, Agricultural/metabolism ; Datasets as Topic ; Forests ; Grassland ; Soil/*chemistry ; Temperature ; Tropical Climate ; }, abstract = {The exchange of carbon between soil organic carbon (SOC) and the atmosphere affects the climate1,2 and-because of the importance of organic matter to soil fertility-agricultural productivity3. The dynamics of topsoil carbon has been relatively well quantified4, but half of the soil carbon is located in deeper soil layers (below 30 centimetres)5-7, and many questions remain regarding the exchange of this deep carbon with the atmosphere8. This knowledge gap restricts soil carbon management policies and limits global carbon models1,9,10. Here we quantify the recent incorporation of atmosphere-derived carbon atoms into whole-soil profiles, through a meta-analysis of changes in stable carbon isotope signatures at 112 grassland, forest and cropland sites, across different climatic zones, from 1965 to 2015. We find, in agreement with previous work5,6, that soil at a depth of 30-100 centimetres beneath the surface (the subsoil) contains on average 47 per cent of the topmost metre's SOC stocks. However, we show that this subsoil accounts for just 19 per cent of the SOC that has been recently incorporated (within the past 50 years) into the topmost metre. Globally, the median depth of recent carbon incorporation into mineral soil is 10 centimetres. Variations in the relative allocation of carbon to deep soil layers are better explained by the aridity index than by mean annual temperature. Land use for crops reduces the incorporation of carbon into the soil surface layer, but not into deeper layers. Our results suggest that SOC dynamics and its responses to climatic control or land use are strongly dependent on soil depth. We propose that using multilayer soil modules in global carbon models, tested with our data, could help to improve our understanding of soil-atmosphere carbon exchange.}, } @article {pmid29995857, year = {2018}, author = {Baradaran, R and Wang, C and Siliciano, AF and Long, SB}, title = {Cryo-EM structures of fungal and metazoan mitochondrial calcium uniporters.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {580-584}, doi = {10.1038/s41586-018-0331-8}, pmid = {29995857}, issn = {1476-4687}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 GM094273/GM/NIGMS NIH HHS/United States ; T32 GM007739/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/chemistry ; Calcium/metabolism ; Calcium Channels/*chemistry/metabolism/*ultrastructure ; *Cryoelectron Microscopy ; Ion Channel Gating ; Models, Molecular ; Phialophora/*chemistry ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; *Zebrafish ; }, abstract = {The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel and a major route of calcium entry into mitochondria. How the channel catalyses ion permeation and achieves ion selectivity are not well understood, partly because MCU is thought to have a distinct architecture in comparison to other cellular channels. Here we report cryo-electron microscopy reconstructions of MCU channels from zebrafish and Cyphellophora europaea at 8.5 Å and 3.2 Å resolutions, respectively. In contrast to a previous report of pentameric stoichiometry for MCU, both channels are tetramers. The atomic model of C. europaea MCU shows that a conserved WDXXEP signature sequence forms the selectivity filter, in which calcium ions are arranged in single file. Coiled-coil legs connect the pore to N-terminal domains in the mitochondrial matrix. In C. europaea MCU, the N-terminal domains assemble as a dimer of dimers; in zebrafish MCU, they form an asymmetric crescent. The structures define principles that underlie ion permeation and calcium selectivity in this unusual channel.}, } @article {pmid29995856, year = {2018}, author = {Fan, C and Fan, M and Orlando, BJ and Fastman, NM and Zhang, J and Xu, Y and Chambers, MG and Xu, X and Perry, K and Liao, M and Feng, L}, title = {X-ray and cryo-EM structures of the mitochondrial calcium uniporter.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {575-579}, doi = {10.1038/s41586-018-0330-9}, pmid = {29995856}, issn = {1476-4687}, support = {P30 GM124165/GM/NIGMS NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/chemistry ; Calcium/metabolism ; Calcium Channels/*chemistry/metabolism/*ultrastructure ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; Fusarium/*chemistry ; Ion Channel Gating ; Metarhizium/*chemistry ; Models, Molecular ; Protein Domains ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Reproducibility of Results ; Solubility ; }, abstract = {Mitochondrial calcium uptake is critical for regulating ATP production, intracellular calcium signalling, and cell death. This uptake is mediated by a highly selective calcium channel called the mitochondrial calcium uniporter (MCU). Here, we determined the structures of the pore-forming MCU proteins from two fungi by X-ray crystallography and single-particle cryo-electron microscopy. The stoichiometry, overall architecture, and individual subunit structure differed markedly from those described in the recent nuclear magnetic resonance structure of Caenorhabditis elegans MCU. We observed a dimer-of-dimer architecture across species and chemical environments, which was corroborated by biochemical experiments. Structural analyses and functional characterization uncovered the roles of key residues in the pore. These results reveal a new ion channel architecture, provide insights into calcium coordination, selectivity and conduction, and establish a structural framework for understanding the mechanism of mitochondrial calcium uniporter function.}, } @article {pmid29995855, year = {2018}, author = {Nguyen, NX and Armache, JP and Lee, C and Yang, Y and Zeng, W and Mootha, VK and Cheng, Y and Bai, XC and Jiang, Y}, title = {Cryo-EM structure of a fungal mitochondrial calcium uniporter.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {570-574}, pmid = {29995855}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; R01 GM079179/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Calcium/metabolism ; Calcium Channels/*chemistry/metabolism/*ultrastructure ; *Cryoelectron Microscopy ; Humans ; Ion Channel Gating/drug effects ; Ion Transport/drug effects ; Models, Molecular ; Neosartorya/*chemistry ; Protein Domains ; Protein Subunits/chemistry/metabolism ; Ruthenium Compounds/pharmacology ; Solubility ; }, abstract = {The mitochondrial calcium uniporter (MCU) is a highly selective calcium channel localized to the inner mitochondrial membrane. Here, we describe the structure of an MCU orthologue from the fungus Neosartorya fischeri (NfMCU) determined to 3.8 Å resolution by phase-plate cryo-electron microscopy. The channel is a homotetramer with two-fold symmetry in its amino-terminal domain (NTD) that adopts a similar structure to that of human MCU. The NTD assembles as a dimer of dimers to form a tetrameric ring that connects to the transmembrane domain through an elongated coiled-coil domain. The ion-conducting pore domain maintains four-fold symmetry, with the selectivity filter positioned at the start of the pore-forming TM2 helix. The aspartate and glutamate sidechains of the conserved DIME motif are oriented towards the central axis and separated by one helical turn. The structure of NfMCU offers insights into channel assembly, selective calcium permeation, and inhibitor binding.}, } @article {pmid29995854, year = {2018}, author = {Loh, PR and Genovese, G and Handsaker, RE and Finucane, HK and Reshef, YA and Palamara, PF and Birmann, BM and Talkowski, ME and Bakhoum, SF and McCarroll, SA and Price, AL}, title = {Insights into clonal haematopoiesis from 8,342 mosaic chromosomal alterations.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {350-355}, pmid = {29995854}, issn = {1476-4687}, support = {R01 GM105857/GM/NIGMS NIH HHS/United States ; R01 HD081256/HD/NICHD NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; }, abstract = {The selective pressures that shape clonal evolution in healthy individuals are largely unknown. Here we investigate 8,342 mosaic chromosomal alterations, from 50 kb to 249 Mb long, that we uncovered in blood-derived DNA from 151,202 UK Biobank participants using phase-based computational techniques (estimated false discovery rate, 6-9%). We found six loci at which inherited variants associated strongly with the acquisition of deletions or loss of heterozygosity in cis. At three such loci (MPL, TM2D3-TARSL2, and FRA10B), we identified a likely causal variant that acted with high penetrance (5-50%). Inherited alleles at one locus appeared to affect the probability of somatic mutation, and at three other loci to be objects of positive or negative clonal selection. Several specific mosaic chromosomal alterations were strongly associated with future haematological malignancies. Our results reveal a multitude of paths towards clonal expansions with a wide range of effects on human health.}, } @article {pmid29995853, year = {2018}, author = {Yen, HY and Hoi, KK and Liko, I and Hedger, G and Horrell, MR and Song, W and Wu, D and Heine, P and Warne, T and Lee, Y and Carpenter, B and Plückthun, A and Tate, CG and Sansom, MSP and Robinson, CV}, title = {PtdIns(4,5)P2 stabilizes active states of GPCRs and enhances selectivity of G-protein coupling.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {423-427}, pmid = {29995853}, issn = {1476-4687}, support = {104633//Wellcome Trust/United Kingdom ; 695511//European Research Council/International ; G1000819//Medical Research Council/United Kingdom ; MR/N020413/1//Medical Research Council/United Kingdom ; 339995//European Research Council/International ; }, abstract = {G-protein-coupled receptors (GPCRs) are involved in many physiological processes and are therefore key drug targets1. Although detailed structural information is available for GPCRs, the effects of lipids on the receptors, and on downstream coupling of GPCRs to G proteins are largely unknown. Here we use native mass spectrometry to identify endogenous lipids bound to three class A GPCRs. We observed preferential binding of phosphatidylinositol-4,5-bisphosphate (PtdIns(4,5)P2) over related lipids and confirm that the intracellular surface of the receptors contain hotspots for PtdIns(4,5)P2 binding. Endogenous lipids were also observed bound directly to the trimeric Gαsβγ protein complex of the adenosine A2A receptor (A2AR) in the gas phase. Using engineered Gα subunits (mini-Gαs, mini-Gαi and mini-Gα12)2, we demonstrate that the complex of mini-Gαs with the β1 adrenergic receptor (β1AR) is stabilized by the binding of two PtdIns(4,5)P2 molecules. By contrast, PtdIns(4,5)P2 does not stabilize coupling between β1AR and other Gα subunits (mini-Gαi or mini-Gα12) or a high-affinity nanobody. Other endogenous lipids that bind to these receptors have no effect on coupling, highlighting the specificity of PtdIns(4,5)P2. Calculations of potential of mean force and increased GTP turnover by the activated neurotensin receptor when coupled to trimeric Gαiβγ complex in the presence of PtdIns(4,5)P2 provide further evidence for a specific effect of PtdIns(4,5)P2 on coupling. We identify key residues on cognate Gα subunits through which PtdIns(4,5)P2 forms bridging interactions with basic residues on class A GPCRs. These modulating effects of lipids on receptors suggest consequences for understanding function, G-protein selectivity and drug targeting of class A GPCRs.}, } @article {pmid29995852, year = {2018}, author = {Kanarek, N and Keys, HR and Cantor, JR and Lewis, CA and Chan, SH and Kunchok, T and Abu-Remaileh, M and Freinkman, E and Schweitzer, LD and Sabatini, DM}, title = {Histidine catabolism is a major determinant of methotrexate sensitivity.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {632-636}, pmid = {29995852}, issn = {1476-4687}, support = {R01 CA129105/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Ammonia-Lyases/deficiency/genetics/metabolism ; Animals ; CRISPR-Cas Systems/genetics ; Cell Line, Tumor ; Female ; Folic Acid Antagonists/pharmacology/therapeutic use ; Glutamate Formimidoyltransferase/deficiency/genetics/metabolism ; Histidine/*metabolism/pharmacology ; Humans ; Male ; Methotrexate/*pharmacology/*therapeutic use ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasms/*drug therapy/*metabolism ; Nucleotides/biosynthesis ; Reduced Folate Carrier Protein/genetics/metabolism ; Tetrahydrofolate Dehydrogenase/metabolism ; Tetrahydrofolates/deficiency/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {The chemotherapeutic drug methotrexate inhibits the enzyme dihydrofolate reductase1, which generates tetrahydrofolate, an essential cofactor in nucleotide synthesis2. Depletion of tetrahydrofolate causes cell death by suppressing DNA and RNA production3. Although methotrexate is widely used as an anticancer agent and is the subject of over a thousand ongoing clinical trials4, its high toxicity often leads to the premature termination of its use, which reduces its potential efficacy5. To identify genes that modulate the response of cancer cells to methotrexate, we performed a CRISPR-Cas9-based screen6,7. This screen yielded FTCD, which encodes an enzyme-formimidoyltransferase cyclodeaminase-that is required for the catabolism of the amino acid histidine8, a process that has not previously been linked to methotrexate sensitivity. In cultured cancer cells, depletion of several genes in the histidine degradation pathway markedly decreased sensitivity to methotrexate. Mechanistically, histidine catabolism drains the cellular pool of tetrahydrofolate, which is particularly detrimental to methotrexate-treated cells. Moreover, expression of the rate-limiting enzyme in histidine catabolism is associated with methotrexate sensitivity in cancer cell lines and with survival rate in patients. In vivo dietary supplementation of histidine increased flux through the histidine degradation pathway and enhanced the sensitivity of leukaemia xenografts to methotrexate. The histidine degradation pathway markedly influences the sensitivity of cancer cells to methotrexate and may be exploited to improve methotrexate efficacy through a simple dietary intervention.}, } @article {pmid29995851, year = {2018}, author = {Qi, X and Schmiege, P and Coutavas, E and Wang, J and Li, X}, title = {Structures of human Patched and its complex with native palmitoylated sonic hedgehog.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {128-132}, doi = {10.1038/s41586-018-0308-7}, pmid = {29995851}, issn = {1476-4687}, support = {P01 HL020948/HL/NHLBI NIH HHS/United States ; }, mesh = {Binding Sites ; Cholesterol/metabolism ; *Cryoelectron Microscopy ; Fatty Acids/metabolism ; Hedgehog Proteins/*chemistry/metabolism/*ultrastructure ; Humans ; Ligands ; *Lipoylation ; Models, Molecular ; Palmitic Acid/*metabolism ; Patched-1 Receptor/*chemistry/*ultrastructure ; Protein Domains ; }, abstract = {Hedgehog (HH) signalling governs embryogenesis and adult tissue homeostasis in mammals and other multicellular organisms1-3. Whereas deficient HH signalling leads to birth defects, unrestrained HH signalling is implicated in human cancers2,4-6. N-terminally palmitoylated HH releases the repression of Patched to the oncoprotein smoothened (SMO); however, the mechanism by which HH recognizes Patched is unclear. Here we report cryo-electron microscopy structures of human patched 1 (PTCH1) alone and in complex with the N-terminal domain of 'native' sonic hedgehog (native SHH-N has both a C-terminal cholesterol and an N-terminal fatty-acid modification), at resolutions of 3.5 Å and 3.8 Å, respectively. The structure of PTCH1 has internal two-fold pseudosymmetry in the transmembrane core, which features a sterol-sensing domain and two homologous extracellular domains, resembling the architecture of Niemann-Pick C1 (NPC1) protein7. The palmitoylated N terminus of SHH-N inserts into a cavity between the extracellular domains of PTCH1 and dominates the PTCH1-SHH-N interface, which is distinct from that reported for SHH-N co-receptors8. Our biochemical assays show that SHH-N may use another interface, one that is required for its co-receptor binding, to recruit PTCH1 in the absence of a covalently attached palmitate. Our work provides atomic insights into the recognition of the N-terminal domain of HH (HH-N) by PTCH1, offers a structural basis for cooperative binding of HH-N to various receptors and serves as a molecular framework for HH signalling and its malfunction in disease.}, } @article {pmid29995850, year = {2018}, author = {Liu, L and Wang, Y and Sinatra, R and Giles, CL and Song, C and Wang, D}, title = {Hot streaks in artistic, cultural, and scientific careers.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {396-399}, doi = {10.1038/s41586-018-0315-8}, pmid = {29995850}, issn = {1476-4687}, abstract = {The hot streak-loosely defined as 'winning begets more winnings'-highlights a specific period during which an individual's performance is substantially better than his or her typical performance. Although hot streaks have been widely debated in sports1,2, gambling3-5 and financial markets6,7 over the past several decades, little is known about whether they apply to individual careers. Here, building on rich literature on the lifecycle of creativity8-22, we collected large-scale career histories of individual artists, film directors and scientists, tracing the artworks, films and scientific publications they produced. We find that, across all three domains, hit works within a career show a high degree of temporal regularity, with each career being characterized by bursts of high-impact works occurring in sequence. We demonstrate that these observations can be explained by a simple hot-streak model, allowing us to probe quantitatively the hot streak phenomenon governing individual careers. We find this phenomemon to be remarkably universal across diverse domains: hot streaks are ubiquitous yet usually unique across different careers. The hot streak emerges randomly within an individual's sequence of works, is temporally localized, and is not associated with any detectable change in productivity. We show that, because works produced during hot streaks garner substantially more impact, the uncovered hot streaks fundamentally drive the collective impact of an individual, and ignoring this leads us to systematically overestimate or underestimate the future impact of a career. These results not only deepen our quantitative understanding of patterns that govern individual ingenuity and success, but also may have implications for identifying and nurturing individuals whose work will have lasting impact.}, } @article {pmid29995849, year = {2018}, author = {Plaschka, C and Lin, PC and Charenton, C and Nagai, K}, title = {Prespliceosome structure provides insights into spliceosome assembly and regulation.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {419-422}, pmid = {29995849}, issn = {1476-4687}, support = {693087//European Research Council/International ; MC_U105184330//Medical Research Council/United Kingdom ; //Medical Research Council/United Kingdom ; //European Research Council/International ; }, abstract = {The spliceosome catalyses the excision of introns from pre-mRNA in two steps, branching and exon ligation, and is assembled from five small nuclear ribonucleoprotein particles (snRNPs; U1, U2, U4, U5, U6) and numerous non-snRNP factors1. For branching, the intron 5' splice site and the branch point sequence are selected and brought by the U1 and U2 snRNPs into the prespliceosome1, which is a focal point for regulation by alternative splicing factors2. The U4/U6.U5 tri-snRNP subsequently joins the prespliceosome to form the complete pre-catalytic spliceosome. Recent studies have revealed the structural basis of the branching and exon-ligation reactions3, however, the structural basis of the early events in spliceosome assembly remains poorly understood4. Here we report the cryo-electron microscopy structure of the yeast Saccharomyces cerevisiae prespliceosome at near-atomic resolution. The structure reveals an induced stabilization of the 5' splice site in the U1 snRNP, and provides structural insights into the functions of the human alternative splicing factors LUC7-like (yeast Luc7) and TIA-1 (yeast Nam8), both of which have been linked to human disease5,6. In the prespliceosome, the U1 snRNP associates with the U2 snRNP through a stable contact with the U2 3' domain and a transient yeast-specific contact with the U2 SF3b-containing 5' region, leaving its tri-snRNP-binding interface fully exposed. The results suggest mechanisms for 5' splice site transfer to the U6 ACAGAGA region within the assembled spliceosome and for its subsequent conversion to the activation-competent B-complex spliceosome7,8. Taken together, the data provide a working model to investigate the early steps of spliceosome assembly.}, } @article {pmid29995848, year = {2018}, author = {Zhu, Z and Dennell, R and Huang, W and Wu, Y and Qiu, S and Yang, S and Rao, Z and Hou, Y and Xie, J and Han, J and Ouyang, T}, title = {Hominin occupation of the Chinese Loess Plateau since about 2.1 million years ago.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {608-612}, doi = {10.1038/s41586-018-0299-4}, pmid = {29995848}, issn = {1476-4687}, mesh = {Animals ; China ; Fossils ; History, Ancient ; *Hominidae ; Paleontology ; }, abstract = {Considerable attention has been paid to dating the earliest appearance of hominins outside Africa. The earliest skeletal and artefactual evidence for the genus Homo in Asia currently comes from Dmanisi, Georgia, and is dated to approximately 1.77-1.85 million years ago (Ma)1. Two incisors that may belong to Homo erectus come from Yuanmou, south China, and are dated to 1.7 Ma2; the next-oldest evidence is an H. erectus cranium from Lantian (Gongwangling)-which has recently been dated to 1.63 Ma3-and the earliest hominin fossils from the Sangiran dome in Java, which are dated to about 1.5-1.6 Ma4. Artefacts from Majuangou III5 and Shangshazui6 in the Nihewan basin, north China, have also been dated to 1.6-1.7 Ma. Here we report an Early Pleistocene and largely continuous artefact sequence from Shangchen, which is a newly discovered Palaeolithic locality of the southern Chinese Loess Plateau, near Gongwangling in Lantian county. The site contains 17 artefact layers that extend from palaeosol S15-dated to approximately 1.26 Ma-to loess L28, which we date to about 2.12 Ma. This discovery implies that hominins left Africa earlier than indicated by the evidence from Dmanisi.}, } @article {pmid29995847, year = {2018}, author = {Parikshak, NN and Swarup, V and Belgard, TG and Irimia, M and Ramaswami, G and Gandal, MJ and Hartl, C and Leppa, V and de la Torre Ubieta, L and Huang, J and Lowe, JK and Blencowe, BJ and Horvath, S and Geschwind, DH}, title = {Author Correction: Genome-wide changes in lncRNA, splicing, and regional gene expression patterns in autism.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {E30}, doi = {10.1038/s41586-018-0295-8}, pmid = {29995847}, issn = {1476-4687}, abstract = {Change history: In this Letter, the labels for splicing events A3SS and A5SS were swapped in column D of Supplementary Table 3a and b. This has been corrected online.}, } @article {pmid29995846, year = {2018}, author = {Gladkova, C and Maslen, SL and Skehel, JM and Komander, D}, title = {Mechanism of parkin activation by PINK1.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {410-414}, pmid = {29995846}, issn = {1476-4687}, support = {309756//European Research Council/International ; MC_U105192732//Medical Research Council/United Kingdom ; }, abstract = {Mutations in the E3 ubiquitin ligase parkin (PARK2, also known as PRKN) and the protein kinase PINK1 (also known as PARK6) are linked to autosomal-recessive juvenile parkinsonism (AR-JP)1,2; at the cellular level, these mutations cause defects in mitophagy, the process that organizes the destruction of damaged mitochondria3,4. Parkin is autoinhibited, and requires activation by PINK1, which phosphorylates Ser65 in ubiquitin and in the parkin ubiquitin-like (Ubl) domain. Parkin binds phospho-ubiquitin, which enables efficient parkin phosphorylation; however, the enzyme remains autoinhibited with an inaccessible active site5,6. It is unclear how phosphorylation of parkin activates the molecule. Here we follow the activation of full-length human parkin by hydrogen-deuterium exchange mass spectrometry, and reveal large-scale domain rearrangement in the activation process, during which the phospho-Ubl rebinds to the parkin core and releases the catalytic RING2 domain. A 1.8 Å crystal structure of phosphorylated human parkin reveals the binding site of the phospho-Ubl on the unique parkin domain (UPD), involving a phosphate-binding pocket lined by AR-JP mutations. Notably, a conserved linker region between Ubl and the UPD acts as an activating element (ACT) that contributes to RING2 release by mimicking RING2 interactions on the UPD, explaining further AR-JP mutations. Our data show how autoinhibition in parkin is resolved, and suggest a mechanism for how parkin ubiquitinates its substrates via an untethered RING2 domain. These findings open new avenues for the design of parkin activators for clinical use.}, } @article {pmid29995837, year = {2018}, author = {Kline, AD and Moss, JF and Selicorni, A and Bisgaard, AM and Deardorff, MA and Gillett, PM and Ishman, SL and Kerr, LM and Levin, AV and Mulder, PA and Ramos, FJ and Wierzba, J and Ajmone, PF and Axtell, D and Blagowidow, N and Cereda, A and Costantino, A and Cormier-Daire, V and FitzPatrick, D and Grados, M and Groves, L and Guthrie, W and Huisman, S and Kaiser, FJ and Koekkoek, G and Levis, M and Mariani, M and McCleery, JP and Menke, LA and Metrena, A and O'Connor, J and Oliver, C and Pie, J and Piening, S and Potter, CJ and Quaglio, AL and Redeker, E and Richman, D and Rigamonti, C and Shi, A and Tümer, Z and Van Balkom, IDC and Hennekam, RC}, title = {Diagnosis and management of Cornelia de Lange syndrome: first international consensus statement.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {10}, pages = {649-666}, doi = {10.1038/s41576-018-0031-0}, pmid = {29995837}, issn = {1471-0064}, abstract = {Cornelia de Lange syndrome (CdLS) is an archetypical genetic syndrome that is characterized by intellectual disability, well-defined facial features, upper limb anomalies and atypical growth, among numerous other signs and symptoms. It is caused by variants in any one of seven genes, all of which have a structural or regulatory function in the cohesin complex. Although recent advances in next-generation sequencing have improved molecular diagnostics, marked heterogeneity exists in clinical and molecular diagnostic approaches and care practices worldwide. Here, we outline a series of recommendations that document the consensus of a group of international experts on clinical diagnostic criteria, both for classic CdLS and non-classic CdLS phenotypes, molecular investigations, long-term management and care planning.}, } @article {pmid29995832, year = {2018}, author = {Holmqvist, E and Vogel, J}, title = {RNA-binding proteins in bacteria.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {601-615}, doi = {10.1038/s41579-018-0049-5}, pmid = {29995832}, issn = {1740-1534}, abstract = {RNA-binding proteins (RBPs) are central to most if not all cellular processes, dictating the fate of virtually all RNA molecules in the cell. Starting with pioneering work on ribosomal proteins, studies of bacterial RBPs have paved the way for molecular studies of RNA-protein interactions. Work over the years has identified major RBPs that act on cellular transcripts at the various stages of bacterial gene expression and that enable their integration into post-transcriptional networks that also comprise small non-coding RNAs. Bacterial RBP research has now entered a new era in which RNA sequencing-based methods permit mapping of RBP activity in a truly global manner in vivo. Moreover, the soaring interest in understudied members of host-associated microbiota and environmental communities is likely to unveil new RBPs and to greatly expand our knowledge of RNA-protein interactions in bacteria.}, } @article {pmid29993124, year = {2018}, author = {Vanhoenacker, E and Sandell, L and Roze, D}, title = {Stabilizing selection, mutational bias, and the evolution of sex.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1740-1758}, doi = {10.1111/evo.13547}, pmid = {29993124}, issn = {1558-5646}, support = {ANR-14-CE02-0001-01//Agence Nationale de la Recherche/ ; }, abstract = {Stabilizing selection around a fixed phenotypic optimum is expected to disfavor sexual reproduction, since asexually reproducing organisms can maintain a higher fitness at equilibrium, while sex disrupts combinations of compensatory mutations. This conclusion rests on the assumption that mutational effects on phenotypic traits are unbiased, that is, mutation does not tend to push phenotypes in any particular direction. In this article, we consider a model of stabilizing selection acting on an arbitrary number of polygenic traits coded by bialellic loci, and show that mutational bias may greatly reduce the mean fitness of asexual populations compared with sexual ones in regimes where mutations have weak to moderate fitness effects. Indeed, mutation and drift tend to push the population mean phenotype away from the optimum, this effect being enhanced by the low effective population size of asexual populations. In a second part, we present results from individual-based simulations showing that positive rates of sex are favored when mutational bias is present, while the population evolves toward complete asexuality in the absence of bias. We also present analytical (QLE) approximations for the selective forces acting on sex in terms of the effect of sex on the mean and variance in fitness among offspring.}, } @article {pmid29993040, year = {2018}, author = {}, title = {Governments must weigh the environmental costs of deep-sea mining.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {152}, doi = {10.1038/d41586-018-05681-1}, pmid = {29993040}, issn = {1476-4687}, mesh = {Conservation of Natural Resources/*legislation & jurisprudence ; Ecosystem ; Environmental Policy/*legislation & jurisprudence ; *Federal Government ; Geologic Sediments/chemistry ; Mining/*legislation & jurisprudence ; *Oceans and Seas ; }, } @article {pmid29993039, year = {2018}, author = {Daar, AS and Chang, T and Salomon, A and Singer, PA}, title = {Grand challenges in humanitarian aid.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {169-173}, doi = {10.1038/d41586-018-05642-8}, pmid = {29993039}, issn = {1476-4687}, mesh = {*Altruism ; Armed Conflicts/economics ; Conflict (Psychology) ; *Goals ; Humans ; Natural Disasters/economics ; Social Sciences/economics/*trends ; }, } @article {pmid29993033, year = {2018}, author = {Clyde, D}, title = {The genetics of loneliness.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {532-533}, doi = {10.1038/s41576-018-0036-8}, pmid = {29993033}, issn = {1471-0064}, } @article {pmid29992728, year = {2018}, author = {Hayakawa, T and Nathan, SKSS and Stark, DJ and Saldivar, DAR and Sipangkui, R and Goossens, B and Tuuga, A and Clauss, M and Sawada, A and Fukuda, S and Imai, H and Matsuda, I}, title = {First report of foregut microbial community in proboscis monkeys: are diverse forests a reservoir for diverse microbiomes?.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {655-662}, doi = {10.1111/1758-2229.12677}, pmid = {29992728}, issn = {1758-2229}, abstract = {Foregut fermentation is well known to occur in a wide range of mammalian species and in a single bird species. Yet, the foregut microbial community of free-ranging, foregut-fermenting monkeys, that is, colobines, has not been investigated so far. We analysed the foregut microbiomes in four free-ranging proboscis monkeys (Nasalis larvatus) from two different tropical habitats with varying plant diversity (mangrove and riverine forests), in an individual from a semi-free-ranging setting with supplemental feeding, and in an individual from captivity, using high-throughput sequencing based on 16S ribosomal RNA genes. We found a decrease in foregut microbial diversity from a diverse natural habitat (riverine forest) to a low diverse natural habitat (mangrove forest), to human-related environments. Of a total of 2700 bacterial operational taxonomic units (OTUs) detected in all environments, only 153 OTUs were shared across all individuals, suggesting that they were not influenced by diet or habitat. These OTUs were dominated by Firmicutes and Proteobacteria. The relative abundance of the habitat-specific microbial communities showed a wide range of differences among living environments, although such bacterial communities appeared to be dominated by Firmicutes and Bacteroidetes, suggesting that those phyla are key to understanding the adaptive strategy in proboscis monkeys living in different habitats.}, } @article {pmid29992542, year = {2018}, author = {Paudel, BR and Burd, M and Shrestha, M and Dyer, AG and Li, QJ}, title = {Reproductive isolation in alpine gingers: How do coexisting Roscoea (R. purpurea and R. tumjensis) conserve species integrity?.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1840-1850}, doi = {10.1111/evo.13546}, pmid = {29992542}, issn = {1558-5646}, support = {(NSFC-YNU, U1602263)//Joint Funds of the National Natural Science Foundation of China/ ; }, abstract = {Multiple barriers may contribute to reproductive isolation between closely related species. Understanding the relative strength of these barriers can illuminate the ecological factors that currently maintain species integrity and how these factors originally promoted speciation. Two Himalayan alpine gingers, Roscoea purpurea and R. tumjensis, occur sympatrically in central Nepal and have such similar morphology that it is not clear whether or how they maintain a distinct identity. Our quantitative measurements of the components of reproductive isolation show that they are, in fact, completely isolated by a combination of phenological displacement of flowering, earlier for R. tumjensis and later for R. purpurea, and complete fidelity of visitation by different pollinator species, bumblebees for R. tumjensis and a long-tongued fly for R. purpurea. Furthermore, the nectar of R. tumjensis flowers is available to the shorter tongued bumblebees while R. purpurea nectar is less accessible, requiring deep probing from long-tongued flies. Although flowering phenology is a strong current barrier that seemingly obviates any need for pollinator discrimination, this current pattern need not reflect selective forces occurring at the initial divergence of R. tumjensis. There has been considerable pollinator switching during the radiation of the Himalayan Roscoea, and the association of flowering time with type of pollinator in these sympatric species may have originated among the earliest or latest flowering individuals or populations of an ancestor to exploit either bumblebee activity early in the breeding season or long-tongued fly abundance later in the season. These two sympatric Roscoea species add to accumulating evidence of the primacy of prezygotic pollination traits in speciation among angiosperms even in the absence of postzygotic incompatibility.}, } @article {pmid29992348, year = {2018}, author = {Tamayo-Ordóñez, YJ and Narváez-Zapata, JA and Tamayo-Ordóñez, MC and Sánchez-Teyer, LF}, title = {Retroelements and DNA Methylation Could Contribute to Diversity of 5S rDNA in Agave L.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {29992348}, issn = {1432-1432}, abstract = {Agave L. is a genus of economic importance, and many of the 166 species in the American plant genus Agave L. inhabit high-stress environments, which makes the genus promising for facing global climate change. However, sustainable use of economically important species without interfering with their ecology and evolution requires generating knowledge about the factors responsible for their genetic variation and diversity and, on this basis, their adaptation and speciation. Few genetic studies exploring the evolutionary relationships, speciation processes, genetic variability and diversity within species of Agave are currently available. Analyses of rDNA loci have been performed with the purpose of determining the genetic variability and diversity of the genus Agave, and these loci have been used as genetic markers of ploidy. However, the factors involved in the diversity of 5S rDNA regions in Agave have not yet been studied in depth. Our study explored the possible mechanisms of genetic (retroelements) and epigenetic (DNA methylation) diversity in 5S rDNA regions in Agave. We characterized the 5S rDNA gene tandem in species of the genus with different ploidy numbers and determined the levels of methylation in 13 haplotypes of 5S rDNA and in four non-transcribed spacers (NTS). Our results showed highly dynamic methylation with a high percentage in haplotypes and NTS of 5S rDNA regions in Agave. The characterization of the 5S rDNA tandem array in Agave revealed vestigial remains of the Cassandra terminal-repeat retrotransposon in miniature (TRIM). Our analysis supported previous results suggesting that in species of Agave L., regulation and diversity of 5S rDNA regions are controlled by coordinated genetic and epigenetic events, which will vary according to the species and the level of ploidy. The artificial pressure to which some agave crops are subjected may affect the mechanisms of evolution of gene 5S rDNA.}, } @article {pmid29991798, year = {2018}, author = {Ma, K and Gong, Y and Aubert, T and Turker, MZ and Kao, T and Doerschuk, PC and Wiesner, U}, title = {Publisher Correction: Self-assembly of highly symmetrical, ultrasmall inorganic cages directed by surfactant micelles.}, journal = {Nature}, volume = {562}, number = {7726}, pages = {E7}, doi = {10.1038/s41586-018-0364-z}, pmid = {29991798}, issn = {1476-4687}, abstract = {Change history: In Fig. 3b of this Letter, the labels for the outer (11.8 nm) and inner (7.4 nm) diameters of the structure were inadvertently omitted. Fig. 3 has been corrected online.}, } @article {pmid29991796, year = {2018}, author = {Maxmen, A}, title = {Coming soon to a lab near you? Genetically modified cannabis.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {162}, doi = {10.1038/d41586-018-05659-z}, pmid = {29991796}, issn = {1476-4687}, mesh = {Biomedical Research/*trends ; Biotechnology/trends ; *Cannabidiol ; Cannabinoids/*biosynthesis/*genetics ; Cannabis/*genetics ; Drug Approval/*legislation & jurisprudence ; Genetic Engineering ; Humans ; *Medical Marijuana ; United States ; United States Food and Drug Administration/*legislation & jurisprudence ; }, } @article {pmid29991795, year = {2018}, author = {Gibney, E}, title = {Foreign-researcher figures stress need for immigration reform before Brexit.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {160-161}, doi = {10.1038/d41586-018-05632-w}, pmid = {29991795}, issn = {1476-4687}, mesh = {Emigration and Immigration/*legislation & jurisprudence ; European Union/*organization & administration ; Foreign Professional Personnel/*legislation & jurisprudence/supply & distribution ; Research Personnel/*legislation & jurisprudence/supply & distribution ; United Kingdom ; }, } @article {pmid29991794, year = {2018}, author = {}, title = {No place for bullies in science.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {151}, doi = {10.1038/d41586-018-05683-z}, pmid = {29991794}, issn = {1476-4687}, mesh = {Academies and Institutes ; Age Factors ; Bullying/*prevention & control/statistics & numerical data ; Female ; Germany ; Humans ; Male ; Mentoring/*standards ; Mentors/*psychology ; Research Personnel/*psychology ; Societies, Scientific ; }, } @article {pmid29991793, year = {2018}, author = {Koppenol, WH and Sies, H}, title = {Two centuries since discovery of dawn-of-life molecule.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {181}, doi = {10.1038/d41586-018-05674-0}, pmid = {29991793}, issn = {1476-4687}, mesh = {Earth (Planet) ; *Hydrogen Peroxide ; *Life ; Photosynthesis ; }, } @article {pmid29991792, year = {2018}, author = {Chandra, S and Susskind, LE}, title = {Now India is electrified, bring on the renewables.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {181}, doi = {10.1038/d41586-018-05676-y}, pmid = {29991792}, issn = {1476-4687}, mesh = {*Conservation of Natural Resources ; India ; *Renewable Energy ; Students ; }, } @article {pmid29991791, year = {2018}, author = {Wood, P}, title = {Justification for the EPA's transparency rule.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {181}, doi = {10.1038/d41586-018-05677-x}, pmid = {29991791}, issn = {1476-4687}, mesh = {*Government Regulation ; United States ; *United States Environmental Protection Agency ; }, } @article {pmid29991790, year = {2018}, author = {Herrick, C}, title = {EPA is open to scrutiny.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {181}, doi = {10.1038/d41586-018-05675-z}, pmid = {29991790}, issn = {1476-4687}, mesh = {*Federal Government ; *United States Environmental Protection Agency ; }, } @article {pmid29991789, year = {2018}, author = {Yaw, A and Prosper, K and Krampa, F and Awandare, GA}, title = {Local diagnostics kits for Africa being developed in Ghana.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {181}, doi = {10.1038/d41586-018-05666-0}, pmid = {29991789}, issn = {1476-4687}, mesh = {Africa ; *Diagnostic Tests, Routine/economics ; Early Diagnosis ; Ghana ; HIV Infections/diagnosis/economics ; Humans ; Malaria/diagnosis/economics ; Tuberculosis/diagnosis/economics ; }, } @article {pmid29991788, year = {2018}, author = {Thirumalai, K}, title = {A fresh take on ancient climate change in the North Pacific.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {185-186}, doi = {10.1038/d41586-018-05614-y}, pmid = {29991788}, issn = {1476-4687}, mesh = {*Climate Change ; Ecosystem ; *Fresh Water ; Oceans and Seas ; Pacific Ocean ; }, } @article {pmid29991787, year = {2018}, author = {Shtengel, K}, title = {The heat is on for Majorana fermions.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {189-190}, doi = {10.1038/d41586-018-05637-5}, pmid = {29991787}, issn = {1476-4687}, } @article {pmid29991786, year = {2018}, author = {Callaway, E}, title = {Controversial CRISPR 'gene drives' tested in mammals for the first time.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {164}, doi = {10.1038/d41586-018-05665-1}, pmid = {29991786}, issn = {1476-4687}, mesh = {Animals ; Animals, Wild/genetics ; *CRISPR-Cas Systems ; Culicidae/genetics ; Female ; Gene Drive Technology/*methods ; *Gene Editing ; Introduced Species ; Malaria/prevention & control/transmission ; Male ; Mice ; Pest Control, Biological/*methods ; Sex Characteristics ; Uncertainty ; }, } @article {pmid29991785, year = {2018}, author = {}, title = {Oestrogen holds promise for diabetes cure.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {155}, doi = {10.1038/d41586-018-05633-9}, pmid = {29991785}, issn = {1476-4687}, mesh = {Diabetes Mellitus ; *Estrogens ; Humans ; Insulin ; *Proinsulin ; }, } @article {pmid29991784, year = {2018}, author = {}, title = {The story of African rice, as told by genomics.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {154}, doi = {10.1038/d41586-018-05635-7}, pmid = {29991784}, issn = {1476-4687}, } @article {pmid29991783, year = {2018}, author = {Abbott, A}, title = {Max Planck astrophysicist at centre of bullying allegations speaks up.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {159-160}, doi = {10.1038/d41586-018-05634-8}, pmid = {29991783}, issn = {1476-4687}, mesh = {Academies and Institutes ; Astronomy/*education ; *Bullying/prevention & control ; *Education, Graduate ; Female ; Germany ; Humans ; Leadership ; Mentoring/standards ; Mentors/*psychology ; Physics/education ; Research Personnel/*psychology ; Students/*psychology ; }, } @article {pmid29991782, year = {2018}, author = {}, title = {Smart molecule aids natural cancer defences.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {155}, doi = {10.1038/d41586-018-05630-y}, pmid = {29991782}, issn = {1476-4687}, } @article {pmid29991781, year = {2018}, author = {}, title = {First portrait of a soot molecule.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {154}, doi = {10.1038/d41586-018-05598-9}, pmid = {29991781}, issn = {1476-4687}, } @article {pmid29991780, year = {2018}, author = {}, title = {Lighting the way to versatile 3D printing.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {155}, doi = {10.1038/d41586-018-05629-5}, pmid = {29991780}, issn = {1476-4687}, mesh = {*Lighting ; *Masks ; Printing ; Printing, Three-Dimensional ; }, } @article {pmid29991779, year = {2018}, author = {}, title = {Koala genome reveals secrets to surviving a deadly diet.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {154}, doi = {10.1038/d41586-018-05597-w}, pmid = {29991779}, issn = {1476-4687}, } @article {pmid29991778, year = {2018}, author = {}, title = {How to tell when there's a baby whale on the way.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {155}, doi = {10.1038/d41586-018-05580-5}, pmid = {29991778}, issn = {1476-4687}, } @article {pmid29991777, year = {2018}, author = {}, title = {Mastering molecules in virtual reality.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {154-155}, doi = {10.1038/d41586-018-05574-3}, pmid = {29991777}, issn = {1476-4687}, } @article {pmid29991776, year = {2018}, author = {}, title = {Mystery of buried children at German 'Stonehenge'.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {155}, doi = {10.1038/d41586-018-05541-y}, pmid = {29991776}, issn = {1476-4687}, } @article {pmid29991604, year = {2018}, author = {Barnett, L and Barrett, AB and Seth, AK}, title = {Misunderstandings regarding the application of Granger causality in neuroscience.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6676-E6677}, pmid = {29991604}, issn = {1091-6490}, mesh = {Algorithms ; Causality ; *Computer Simulation ; *Neurosciences ; }, } @article {pmid29991603, year = {2018}, author = {Stokes, PA and Purdon, PL}, title = {Reply to Barnett et al.: Regarding interpretation of Granger causality analyses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6678-E6679}, pmid = {29991603}, issn = {1091-6490}, mesh = {*Brain ; Causality ; Models, Neurological ; *Models, Statistical ; }, } @article {pmid29991602, year = {2018}, author = {Kong, CHT and Rog-Zielinska, EA and Kohl, P and Orchard, CH and Cannell, MB}, title = {Solute movement in the t-tubule system of rabbit and mouse cardiomyocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7073-E7080}, pmid = {29991602}, issn = {1091-6490}, support = {PG/14/42/30886//British Heart Foundation/United Kingdom ; MR/N002903/1//Medical Research Council/United Kingdom ; FS/12/17/29532//British Heart Foundation/United Kingdom ; RG/12/10/29802//British Heart Foundation/United Kingdom ; FS/15/3/31047//British Heart Foundation/United Kingdom ; }, mesh = {Animals ; Biological Transport, Active/physiology ; Heart Ventricles/cytology/metabolism ; Male ; Mice ; *Models, Cardiovascular ; Myocytes, Cardiac/cytology/*metabolism ; Rabbits ; }, abstract = {Cardiac transverse (t-) tubules carry both electrical excitation and solutes toward the cell center but their ability to transport small molecules is unclear. While fluorescence recovery after photobleaching (FRAP) can provide an approach to measure local solute movement, extraction of diffusion coefficients is confounded by cell and illumination beam geometries. In this study, we use measured cellular geometry and detailed computer modeling to derive the apparent diffusion coefficient of a 1-kDa solute inside the t-tubular system of rabbit and mouse ventricular cardiomyocytes. This approach shows that diffusion within individual t-tubules is more rapid than previously reported. T-tubule tortuosity, varicosities, and the presence of longitudinal elements combine to substantially reduce the apparent rate of solute movement. In steady state, large (>4 kDa) solutes did not freely fill the t-tubule lumen of both species and <50% of the t-tubule volume was available to solutes >70 kDa. Detailed model fitting of FRAP data suggests that solute diffusion is additionally restricted at the t-tubular entrance and this effect was larger in mouse than in rabbit. The possible structural basis of this effect was investigated using electron microscopy and tomography. Near the cell surface, mouse t-tubules are more tortuous and filled with an electron-dense ground substance, previously identified as glycocalyx and a polyanionic mesh. Solute movement in the t-tubule network of rabbit and mouse appears to be explained by their different geometric properties, which impacts the use of these species for understanding t-tubule function and the consequences of changes associated with t-tubule disease.}, } @article {pmid29991601, year = {2018}, author = {Welkie, DG and Rubin, BE and Chang, YG and Diamond, S and Rifkin, SA and LiWang, A and Golden, SS}, title = {Genome-wide fitness assessment during diurnal growth reveals an expanded role of the cyanobacterial circadian clock protein KaiA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7174-E7183}, pmid = {29991601}, issn = {1091-6490}, support = {R01 GM107521/GM/NIGMS NIH HHS/United States ; R35 GM118290/GM/NIGMS NIH HHS/United States ; T32 GM007240/GM/NIGMS NIH HHS/United States ; }, mesh = {*Bacterial Proteins/metabolism ; Circadian Clocks/*physiology ; *Circadian Rhythm Signaling Peptides and Proteins/metabolism ; *Genome-Wide Association Study ; Photosynthesis/*physiology ; Signal Transduction/*physiology ; *Synechococcus/genetics/metabolism ; }, abstract = {The recurrent pattern of light and darkness generated by Earth's axial rotation has profoundly influenced the evolution of organisms, selecting for both biological mechanisms that respond acutely to environmental changes and circadian clocks that program physiology in anticipation of daily variations. The necessity to integrate environmental responsiveness and circadian programming is exemplified in photosynthetic organisms such as cyanobacteria, which depend on light-driven photochemical processes. The cyanobacterium Synechococcus elongatus PCC 7942 is an excellent model system for dissecting these entwined mechanisms. Its core circadian oscillator, consisting of three proteins, KaiA, KaiB, and KaiC, transmits time-of-day signals to clock-output proteins, which reciprocally regulate global transcription. Research performed under constant light facilitates analysis of intrinsic cycles separately from direct environmental responses but does not provide insight into how these regulatory systems are integrated during light-dark cycles. Thus, we sought to identify genes that are specifically necessary in a day-night environment. We screened a dense bar-coded transposon library in both continuous light and daily cycling conditions and compared the fitness consequences of loss of each nonessential gene in the genome. Although the clock itself is not essential for viability in light-dark cycles, the most detrimental mutations revealed by the screen were those that disrupt KaiA. The screen broadened our understanding of light-dark survival in photosynthetic organisms, identified unforeseen clock-protein interaction dynamics, and reinforced the role of the clock as a negative regulator of a nighttime metabolic program that is essential for S. elongatus to survive in the dark.}, } @article {pmid29991600, year = {2018}, author = {Skene, DJ and Skornyakov, E and Chowdhury, NR and Gajula, RP and Middleton, B and Satterfield, BC and Porter, KI and Van Dongen, HPA and Gaddameedhi, S}, title = {Separation of circadian- and behavior-driven metabolite rhythms in humans provides a window on peripheral oscillators and metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7825-7830}, pmid = {29991600}, issn = {1091-6490}, support = {R00 ES022640/ES/NIEHS NIH HHS/United States ; BB/I019405/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adult ; Biological Clocks/*physiology ; Circadian Rhythm/*physiology ; Fasting/*blood ; Female ; Gene Expression Regulation/*physiology ; Humans ; Hydrocortisone/*blood ; Male ; Melatonin/*blood ; Period Circadian Proteins/*biosynthesis ; }, abstract = {Misalignment between internal circadian rhythmicity and externally imposed behavioral schedules, such as occurs in shift workers, has been implicated in elevated risk of metabolic disorders. To determine underlying mechanisms, it is essential to assess whether and how peripheral clocks are disturbed during shift work and to what extent this is linked to the central suprachiasmatic nuclei (SCN) pacemaker and/or misaligned behavioral time cues. Investigating rhythms in circulating metabolites as biomarkers of peripheral clock disturbances may offer new insights. We evaluated the impact of misaligned sleep/wake and feeding/fasting cycles on circulating metabolites using a targeted metabolomics approach. Sequential plasma samples obtained during a 24-h constant routine that followed a 3-d simulated night-shift schedule, compared with a simulated day-shift schedule, were analyzed for 132 circulating metabolites. Nearly half of these metabolites showed a 24-h rhythmicity under constant routine following either or both simulated shift schedules. However, while traditional markers of the circadian clock in the SCN-melatonin, cortisol, and PER3 expression-maintained a stable phase alignment after both schedules, only a few metabolites did the same. Many showed reversed rhythms, lost their rhythms, or showed rhythmicity only under constant routine following the night-shift schedule. Here, 95% of the metabolites with a 24-h rhythmicity showed rhythms that were driven by behavioral time cues externally imposed during the preceding simulated shift schedule rather than being driven by the central SCN circadian clock. Characterization of these metabolite rhythms will provide insight into the underlying mechanisms linking shift work and metabolic disorders.}, } @article {pmid29991599, year = {2018}, author = {Mutlu, BR and Edd, JF and Toner, M}, title = {Oscillatory inertial focusing in infinite microchannels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7682-7687}, pmid = {29991599}, issn = {1091-6490}, support = {P41 EB002503/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; *Blood Platelets ; *Exosomes ; Humans ; *Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques/instrumentation/*methods ; *Models, Theoretical ; Particle Size ; *Staphylococcus aureus ; }, abstract = {Inertial microfluidics (i.e., migration and focusing of particles in finite Reynolds number microchannel flows) is a passive, precise, and high-throughput method for microparticle manipulation and sorting. Therefore, it has been utilized in numerous biomedical applications including phenotypic cell screening, blood fractionation, and rare-cell isolation. Nonetheless, the applications of this technology have been limited to larger bioparticles such as blood cells, circulating tumor cells, and stem cells, because smaller particles require drastically longer channels for inertial focusing, which increases the pressure requirement and the footprint of the device to the extent that the system becomes unfeasible. Inertial manipulation of smaller bioparticles such as fungi, bacteria, viruses, and other pathogens or blood components such as platelets and exosomes is of significant interest. Here, we show that using oscillatory microfluidics, inertial focusing in practically "infinite channels" can be achieved, allowing for focusing of micron-scale (i.e. hundreds of nanometers) particles. This method enables manipulation of particles at extremely low particle Reynolds number (Rep < 0.005) flows that are otherwise unattainable by steady-flow inertial microfluidics (which has been limited to Rep > ∼10-1). Using this technique, we demonstrated that synthetic particles as small as 500 nm and a submicron bacterium, Staphylococcus aureus, can be inertially focused. Furthermore, we characterized the physics of inertial microfluidics in this newly enabled particle size and Rep range using a Peclet-like dimensionless number (α). We experimentally observed that α > 1 is required to overcome diffusion and be able to inertially manipulate particles.}, } @article {pmid29991598, year = {2018}, author = {Katz, E and Stoler, O and Scheller, A and Khrapunsky, Y and Goebbels, S and Kirchhoff, F and Gutnick, MJ and Wolf, F and Fleidervish, IA}, title = {Role of sodium channel subtype in action potential generation by neocortical pyramidal neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7184-E7192}, pmid = {29991598}, issn = {1091-6490}, mesh = {Action Potentials/*physiology ; Animals ; Axons/*metabolism ; Gene Deletion ; Mice ; Mice, Transgenic ; NAV1.2 Voltage-Gated Sodium Channel/genetics/*metabolism ; NAV1.6 Voltage-Gated Sodium Channel/genetics/*metabolism ; Neocortex/cytology/*metabolism ; Pyramidal Cells/cytology/*metabolism ; }, abstract = {Neocortical pyramidal neurons express several distinct subtypes of voltage-gated Na+ channels. In mature cells, Nav1.6 is the dominant channel subtype in the axon initial segment (AIS) as well as in the nodes of Ranvier. Action potentials (APs) are initiated in the AIS, and it has been proposed that the high excitability of this region is related to the unique characteristics of the Nav1.6 channel. Knockout or loss-of-function mutation of the Scn8a gene is generally lethal early in life because of the importance of this subtype in noncortical regions of the nervous system. Using the Cre/loxP system, we selectively deleted Nav1.6 in excitatory neurons of the forebrain and characterized the excitability of Nav1.6-deficient layer 5 pyramidal neurons by patch-clamp and Na+ and Ca2+ imaging recordings. We now report that, in the absence of Nav1.6 expression, the AIS is occupied by Nav1.2 channels. However, APs are generated in the AIS, and differences in AP propagation to soma and dendrites are minimal. Moreover, the channels that are expressed in the AIS still show a clear hyperpolarizing shift in voltage dependence of activation, compared with somatic channels. The only major difference between Nav1.6-null and wild-type neurons was a strong reduction in persistent sodium current. We propose that the molecular environment of the AIS confers properties on whatever Na channel subtype is present and that some other benefit must be conferred by the selective axonal presence of the Nav1.6 channel.}, } @article {pmid29991597, year = {2018}, author = {Brincat, SL and Siegel, M and von Nicolai, C and Miller, EK}, title = {Gradual progression from sensory to task-related processing in cerebral cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7202-E7211}, pmid = {29991597}, issn = {1091-6490}, support = {R37 MH087027/MH/NIMH NIH HHS/United States ; RF1 MH114277/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cognition/*physiology ; Color Perception/*physiology ; Female ; Macaca mulatta ; Male ; Prefrontal Cortex/cytology/*physiology ; Problem Solving/*physiology ; }, abstract = {Somewhere along the cortical hierarchy, behaviorally relevant information is distilled from raw sensory inputs. We examined how this transformation progresses along multiple levels of the hierarchy by comparing neural representations in visual, temporal, parietal, and frontal cortices in monkeys categorizing across three visual domains (shape, motion direction, and color). Representations in visual areas middle temporal (MT) and V4 were tightly linked to external sensory inputs. In contrast, lateral prefrontal cortex (PFC) largely represented the abstracted behavioral relevance of stimuli (task rule, motion category, and color category). Intermediate-level areas, including posterior inferotemporal (PIT), lateral intraparietal (LIP), and frontal eye fields (FEF), exhibited mixed representations. While the distribution of sensory information across areas aligned well with classical functional divisions (MT carried stronger motion information, and V4 and PIT carried stronger color and shape information), categorical abstraction did not, suggesting these areas may participate in different networks for stimulus-driven and cognitive functions. Paralleling these representational differences, the dimensionality of neural population activity decreased progressively from sensory to intermediate to frontal cortex. This shows how raw sensory representations are transformed into behaviorally relevant abstractions and suggests that the dimensionality of neural activity in higher cortical regions may be specific to their current task.}, } @article {pmid29991596, year = {2018}, author = {Prots, I and Grosch, J and Brazdis, RM and Simmnacher, K and Veber, V and Havlicek, S and Hannappel, C and Krach, F and Krumbiegel, M and Schütz, O and Reis, A and Wrasidlo, W and Galasko, DR and Groemer, TW and Masliah, E and Schlötzer-Schrehardt, U and Xiang, W and Winkler, J and Winner, B}, title = {α-Synuclein oligomers induce early axonal dysfunction in human iPSC-based models of synucleinopathies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7813-7818}, pmid = {29991596}, issn = {1091-6490}, mesh = {*Axonal Transport ; Axons/*metabolism/pathology ; Cell Line ; Energy Metabolism/genetics ; Humans ; Induced Pluripotent Stem Cells/*metabolism/pathology ; Microtubule-Associated Proteins/genetics/metabolism ; Mitochondria/genetics/metabolism/pathology ; Mitochondrial Proteins/genetics/metabolism ; *Models, Biological ; Mutation, Missense ; Neurodegenerative Diseases/genetics/*metabolism/pathology ; *Protein Multimerization ; alpha-Synuclein ; rho GTP-Binding Proteins/genetics/metabolism ; tau Proteins/genetics/metabolism ; }, abstract = {α-Synuclein (α-Syn) aggregation, proceeding from oligomers to fibrils, is one central hallmark of neurodegeneration in synucleinopathies. α-Syn oligomers are toxic by triggering neurodegenerative processes in in vitro and in vivo models. However, the precise contribution of α-Syn oligomers to neurite pathology in human neurons and the underlying mechanisms remain unclear. Here, we demonstrate the formation of oligomeric α-Syn intermediates and reduced axonal mitochondrial transport in human neurons derived from induced pluripotent stem cells (iPSC) from a Parkinson's disease patient carrying an α-Syn gene duplication. We further show that increased levels of α-Syn oligomers disrupt axonal integrity in human neurons. We apply an α-Syn oligomerization model by expressing α-Syn oligomer-forming mutants (E46K and E57K) and wild-type α-Syn in human iPSC-derived neurons. Pronounced α-Syn oligomerization led to impaired anterograde axonal transport of mitochondria, which can be restored by the inhibition of α-Syn oligomer formation. Furthermore, α-Syn oligomers were associated with a subcellular relocation of transport-regulating proteins Miro1, KLC1, and Tau as well as reduced ATP levels, underlying axonal transport deficits. Consequently, reduced axonal density and structural synaptic degeneration were observed in human neurons in the presence of high levels of α-Syn oligomers. Together, increased dosage of α-Syn resulting in α-Syn oligomerization causes axonal transport disruption and energy deficits, leading to synapse loss in human neurons. This study identifies α-Syn oligomers as the critical species triggering early axonal dysfunction in synucleinopathies.}, } @article {pmid29991573, year = {2018}, author = {Lester, SE and Gentry, RR and Kappel, CV and White, C and Gaines, SD}, title = {Opinion: Offshore aquaculture in the United States: Untapped potential in need of smart policy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7162-7165}, pmid = {29991573}, issn = {1091-6490}, mesh = {*Ecosystem ; Fisheries/*economics/*trends ; Humans ; Oceans and Seas ; Seafood/*economics ; United States ; }, } @article {pmid29991352, year = {2018}, author = {Vidulin, V and Šmuc, T and Džeroski, S and Supek, F}, title = {The evolutionary signal in metagenome phyletic profiles predicts many gene functions.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {129}, pmid = {29991352}, issn = {2049-2618}, mesh = {Evolution, Molecular ; Gene Ontology ; Genomics ; Humans ; Metagenomics/*methods ; *Multigene Family ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; Water Microbiology ; }, abstract = {BACKGROUND: The function of many genes is still not known even in model organisms. An increasing availability of microbiome DNA sequencing data provides an opportunity to infer gene function in a systematic manner.

RESULTS: We evaluated if the evolutionary signal contained in metagenome phyletic profiles (MPP) is predictive of a broad array of gene functions. The MPPs are an encoding of environmental DNA sequencing data that consists of relative abundances of gene families across metagenomes. We find that such MPPs can accurately predict 826 Gene Ontology functional categories, while drawing on human gut microbiomes, ocean metagenomes, and DNA sequences from various other engineered and natural environments. Overall, in this task, the MPPs are highly accurate, and moreover they provide coverage for a set of Gene Ontology terms largely complementary to standard phylogenetic profiles, derived from fully sequenced genomes. We also find that metagenomes approximated from taxon relative abundance obtained via 16S rRNA gene sequencing may provide surprisingly useful predictive models. Crucially, the MPPs derived from different types of environments can infer distinct, non-overlapping sets of gene functions and therefore complement each other. Consistently, simulations on > 5000 metagenomes indicate that the amount of data is not in itself critical for maximizing predictive accuracy, while the diversity of sampled environments appears to be the critical factor for obtaining robust models.

CONCLUSIONS: In past work, metagenomics has provided invaluable insight into ecology of various habitats, into diversity of microbial life and also into human health and disease mechanisms. We propose that environmental DNA sequencing additionally constitutes a useful tool to predict biological roles of genes, yielding inferences out of reach for existing comparative genomics approaches.}, } @article {pmid29991350, year = {2018}, author = {Haro-Moreno, JM and López-Pérez, M and de la Torre, JR and Picazo, A and Camacho, A and Rodriguez-Valera, F}, title = {Fine metagenomic profile of the Mediterranean stratified and mixed water columns revealed by assembly and recruitment.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {128}, pmid = {29991350}, issn = {2049-2618}, mesh = {Archaea/*classification/isolation & purification ; Bacteria/*classification/isolation & purification ; Mediterranean Sea ; Metagenomics/*methods ; Phylogeny ; Seasons ; Water Microbiology ; }, abstract = {BACKGROUND: The photic zone of aquatic habitats is subjected to strong physicochemical gradients. To analyze the fine-scale variations in the marine microbiome, we collected seven samples from a single offshore location in the Mediterranean at 15 m depth intervals during a period of strong stratification, as well as two more samples during the winter when the photic water column was mixed. We were able to recover 94 new metagenome-assembled genomes (MAGs) from these metagenomes and examine the distribution of key marine microbes within the photic zone using metagenomic recruitment.

RESULTS: Our results showed significant differences in the microbial composition of different layers within the stratified photic water column. The majority of microorganisms were confined to discreet horizontal layers of no more than 30 m (stenobathic). Only a few such as members of the SAR11 clade appeared at all depths (eurybathic). During the winter mixing period, only some groups of bloomers such as Pseudomonas were favored. Although most microbes appeared in both seasons, some groups like the SAR116 clade and some Bacteroidetes and Verrucomicrobia seemed to disappear during the mixing period. Furthermore, we found that some microbes previously considered seasonal (e.g., Archaea or Actinobacteria) were living in deeper layers within the photic zone during the stratification period. A strong depth-related specialization was detected, not only at the taxonomic level but also at the functional level, even within the different clades, for the manipulation and uptake of specific polysaccharides. Rhodopsin sequences (green or blue) also showed narrow depth distributions that correlated with the taxonomy of the microbe in which they were found but not with depth.

CONCLUSIONS: Although limited to a single location in the Mediterranean, this study has profound implications for our understanding of how marine microbial communities vary with depth within the photic zone when stratified. Our results highlight the importance of collecting samples at different depths in the water column when comparing seasonal variations and have important ramifications for global marine studies that most often take samples from only one single depth. Furthermore, our perspective and approaches (metagenomic assembly and recruitment) are broadly applicable to other metagenomic studies.}, } @article {pmid29990475, year = {2018}, author = {Chapman, H and Riesenberg, A and Ehrman, LA and Kohli, V and Nardini, D and Nakafuku, M and Campbell, K and Waclaw, RR}, title = {Gsx transcription factors control neuronal versus glial specification in ventricular zone progenitors of the mouse lateral ganglionic eminence.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {115-126}, pmid = {29990475}, issn = {1095-564X}, support = {R01 NS044080/NS/NINDS NIH HHS/United States ; R01 NS069893/NS/NINDS NIH HHS/United States ; R01 NS088529/NS/NINDS NIH HHS/United States ; T32 ES007051/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics/physiology ; Cell Lineage ; Embryo, Mammalian/metabolism ; Ganglia/metabolism/physiology ; Homeodomain Proteins/*genetics/metabolism ; Mice ; Mice, Transgenic ; Neural Stem Cells/cytology ; Neurogenesis/physiology ; Neuroglia/metabolism/physiology ; Neurons/metabolism/physiology ; Oligodendrocyte Transcription Factor 2 ; Oligodendroglia/cytology/physiology ; Stem Cells/metabolism/physiology ; Telencephalon/metabolism ; Transcription Factors ; }, abstract = {The homeobox gene Gsx2 has previously been shown to inhibit oligodendroglial specification in dorsal lateral ganglionic eminence (dLGE) progenitors of the ventral telencephalon. The precocious specification of oligodendrocyte progenitor cells (OPCs) observed in Gsx2 mutants, however, is transient and begins to normalize by late stages of embryogenesis. Interestingly, this normalization correlates with the expansion of Gsx1, a close homolog of Gsx2, in a subset of progenitors in the Gsx2 mutant LGE. Here, we interrogated the mechanisms underlying oligodendroglial specification in Gsx2 mutants in relation to Gsx1. We found that Gsx1/2 double mutant embryos exhibit a more robust expansion of Olig2+ cells (i.e. OPCs) in the subventricular zone (SVZ) of the dLGE than Gsx2 mutants. Moreover, misexpression of Gsx1 throughout telencephalic VZ progenitors from E15 and onward resulted in a significant reduction of cortical OPCs. These results demonstrate redundant roles of Gsx1 and Gsx2 in suppressing early OPC specification in LGE VZ progenitors. However, Gsx1/2 mutants did not show a significant increase in adjacent cortical OPCs at later stages compared to Gsx2 mutants. This is likely due to reduced proliferation of OPCs within the SVZ of the Gsx1/2 double mutant LGE, suggesting a novel role for Gsx1 in expansion of migrating OPCs in the ventral telencephalon. We further investigated the glial specification mechanisms downstream of Gsx2 by generating Olig2/Gsx2 double mutants. Consistent with the known essential role for Olig2 in OPC specification, ectopic production of cortical OPCs observed in Gsx2 mutants disappeared in Olig2/Gsx2 double mutants. These mutants, however, maintained the expanded expression of gliogenic markers Zbtb20 and Bcan in the VZ of the LGE similarly to Gsx2 single mutants, suggesting that Gsx2 suppresses gliogenesis via Olig2-dependent and -independent mechanisms.}, } @article {pmid29989333, year = {2018}, author = {Kramer, J and Meunier, J}, title = {The other facets of family life and their role in the evolution of animal sociality.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12443}, pmid = {29989333}, issn = {1469-185X}, abstract = {Family life forms an integral part of the life history of species across the animal kingdom and plays a crucial role in the evolution of animal sociality. Our current understanding of family life, however, is almost exclusively based on studies that (i) focus on parental care and associated family interactions (such as those arising from sibling rivalry and parent-offspring conflict), and (ii) investigate these phenomena in the advanced family systems of mammals, birds, and eusocial insects. Here, we argue that these historical biases have fostered the neglect of key processes shaping social life in ancestral family systems, and thus profoundly hamper our understanding of the (early) evolution of family life. Based on a comprehensive survey of the literature, we first illustrate that the strong focus on parental care in advanced social systems has deflected scrutiny of other important social processes such as sibling cooperation, parent-offspring competition and offspring assistance. We then show that accounting for these neglected processes - and their changing role over time - could profoundly alter our understanding of the origin and subsequent evolution of family life. Finally, we outline how this 'diachronic' perspective on the evolution of family living provides novel insights into general processes driving the evolution of animal sociality. Overall, we infer that the explicit consideration of thus-far neglected facets of family life, together with their study across the whole diversity of family systems, are crucial to advance our understanding of the processes that shape the evolution of social life.}, } @article {pmid29989317, year = {2018}, author = {Legendre, F and Grandcolas, P}, title = {The evolution of sociality in termites from cockroaches: A taxonomic and phylogenetic perspective.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {5}, pages = {279-287}, doi = {10.1002/jez.b.22812}, pmid = {29989317}, issn = {1552-5015}, abstract = {Despite multiple studies and advances, sociality still puzzles evolutionary biologists in numerous ways, which might be partly addressed with the advent of sociogenomics. In insects, the majority of sociogenomic studies deal with Hymenoptera, one of the two groups that evolved eusociality with termites. But, to fully grasp the evolution of sociality, studies must obviously not restrict to eusocial lineages. Multiple kinds of social system transitions have been recorded and they all bring complementary insights. For instance, cockroaches, the closest relatives to termites, display a wide range of social interactions and evolved convergently subsocial behaviors (i.e., brood care). In this context, we emphasize the need for natural history, taxonomic, and phylogenetic studies. Natural history studies provide the foundations on which building hypotheses, whereas taxonomy provides the taxa to sample to test these hypotheses, and phylogenetics brings the historical framework necessary to test evolutionary scenarios of sociality evolution.}, } @article {pmid29989284, year = {2018}, author = {Figon, F and Casas, J}, title = {Ommochromes in invertebrates: biochemistry and cell biology.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12441}, pmid = {29989284}, issn = {1469-185X}, abstract = {Ommochromes are widely occurring coloured molecules of invertebrates, arising from tryptophan catabolism through the so-called Tryptophan → Ommochrome pathway. They are mainly known to mediate compound eye vision, as well as reversible and irreversible colour patterning. Ommochromes might also be involved in cell homeostasis by detoxifying free tryptophan and buffering oxidative stress. These biological functions are directly linked to their unique chromophore, the phenoxazine/phenothiazine system. The most recent reviews on ommochrome biochemistry were published more than 30 years ago, since when new results on the enzymes of the ommochrome pathway, on ommochrome photochemistry as well as on their antiradical capacities have been obtained. Ommochromasomes are the organelles where ommochromes are synthesised and stored. Hence, they play an important role in mediating ommochrome functions. Ommochromasomes are part of the lysosome-related organelles (LROs) family, which includes other pigmented organelles such as vertebrate melanosomes. Ommochromasomes are unique because they are the only LRO for which a recycling process during reversible colour change has been described. Herein, we provide an update on ommochrome biochemistry, photoreactivity and antiradical capacities to explain their diversity and behaviour both in vivo and in vitro. We also highlight new biochemical techniques, such as quantum chemistry, metabolomics and crystallography, which could lead to major advances in their chemical and functional characterisation. We then focus on ommochromasome structure and formation by drawing parallels with the well-characterised melanosomes of vertebrates. The biochemical, genetic, cellular and microscopic tools that have been applied to melanosomes should provide important information on the ommochromasome life cycle. We propose LRO-based models for ommochromasome biogenesis and recycling that could be tested in the future. Using the context of insect compound eyes, we finally emphasise the importance of an integrated approach in understanding the biological functions of ommochromes.}, } @article {pmid29988462, year = {2018}, author = {Karvonen, A and Lindström, K}, title = {Spatiotemporal and gender-specific parasitism in two species of gobiid fish.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6114-6123}, pmid = {29988462}, issn = {2045-7758}, abstract = {Parasitism is considered a major selective force in natural host populations. Infections can decrease host condition and vigour, and potentially influence, for example, host population dynamics and behavior such as mate choice. We studied parasite infections of two common marine fish species, the sand goby (Pomatoschistus minutus) and the common goby (Pomatoschistus microps), in the brackish water Northern Baltic Sea. We were particularly interested in the occurrence of parasite taxa located in central sensory organs, such as eyes, potentially affecting fish behavior and mate choice. We found that both fish species harbored parasite communities dominated by taxa transmitted to fish through aquatic invertebrates. Infections also showed significant spatiotemporal variation. Trematodes in the eyes were very few in some locations, but infection levels were higher among females than males, suggesting differences in exposure or resistance between the sexes. To test between these hypotheses, we experimentally exposed male and female sand gobies to infection with the eye fluke Diplostomum pseudospathaceum. These trials showed that the fish became readily infected and females had higher parasite numbers, supporting higher susceptibility of females. Eye fluke infections also caused high cataract intensities among the fish in the wild. Our results demonstrate the potential of these parasites to influence host condition and visual abilities, which may have significant implications for survival and mate choice in goby populations.}, } @article {pmid29988460, year = {2018}, author = {Romba, R and Gnankine, O and Drabo, SF and Tiendrebeogo, F and Henri, H and Mouton, L and Vavre, F}, title = {Abundance of Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) and its parasitoids on vegetables and cassava plants in Burkina Faso (West Africa).}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6091-6103}, pmid = {29988460}, issn = {2045-7758}, abstract = {The whitefly Bemisia tabaci is a pest of many agricultural and ornamental crops worldwide and particularly in Africa. It is a complex of cryptic species, which is extremely polyphagous with hundreds of host plants identified around the world. Previous surveys in western Africa indicated the presence of two biotypes of the invasive MED species (MED-Q1 and MED-Q3) living in sympatry with the African species SSA and ASL. This situation constitutes one of the rare cases of local coexistence of various genetic entities within the B. tabaci complex. In order to study the dynamics of the distribution and abundance of genetic entities within this community and to identify potential factors that could contribute to coexistence, we sampled B. tabaci populations in Burkina Faso in 2015 and 2016 on various plants, and also their parasitoids. All four genetic entities were still recorded, indicating no exclusion of local species by the MED species. While B. tabaci individuals were found on 55 plant species belonging to eighteen (18) families showing the high polyphagy of this pest, some species/biotypes exhibited higher specificity. Two parasitoid species (Eretmocerus mundus and Encarsia vandrieschei) were also recorded with E. mundus being predominant in most localities and on most plants. Our data indicated that whitefly abundance, diversity, and rate of parasitism varied according to areas, plants, and years, but that parasitism rate was globally highly correlated with whitefly abundance suggesting density dependence. Our results also suggest dynamic variation in the local diversity of B. tabaci species/biotypes from 1 year to the other, specifically with MED-Q1 and ASL species. This work provides relevant information on the nature of plant-B. tabaci-parasitoid interactions in West Africa and identifies that coexistence might be stabilized by niche differentiation for some genetic entities. However, MED-Q1 and ASL show extensive niche overlap, which could ultimately lead to competitive exclusion.}, } @article {pmid29988457, year = {2018}, author = {van Velzen, E and Gaedke, U}, title = {Reversed predator-prey cycles are driven by the amplitude of prey oscillations.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6317-6329}, pmid = {29988457}, issn = {2045-7758}, abstract = {Ecoevolutionary feedbacks in predator-prey systems have been shown to qualitatively alter predator-prey dynamics. As a striking example, defense-offense coevolution can reverse predator-prey cycles, so predator peaks precede prey peaks rather than vice versa. However, this has only rarely been shown in either model studies or empirical systems. Here, we investigate whether this rarity is a fundamental feature of reversed cycles by exploring under which conditions they should be found. For this, we first identify potential conditions and parameter ranges most likely to result in reversed cycles by developing a new measure, the effective prey biomass, which combines prey biomass with prey and predator traits, and represents the prey biomass as perceived by the predator. We show that predator dynamics always follow the dynamics of the effective prey biomass with a classic ¼-phase lag. From this key insight, it follows that in reversed cycles (i.e., ¾-lag), the dynamics of the actual and the effective prey biomass must be in antiphase with each other, that is, the effective prey biomass must be highest when actual prey biomass is lowest, and vice versa. Based on this, we predict that reversed cycles should be found mainly when oscillations in actual prey biomass are small and thus have limited impact on the dynamics of the effective prey biomass, which are mainly driven by trait changes. We then confirm this prediction using numerical simulations of a coevolutionary predator-prey system, varying the amplitude of the oscillations in prey biomass: Reversed cycles are consistently associated with regions of parameter space leading to small-amplitude prey oscillations, offering a specific and highly testable prediction for conditions under which reversed cycles should occur in natural systems.}, } @article {pmid29988456, year = {2018}, author = {Fellous, A and Labed-Veydert, T and Locrel, M and Voisin, AS and Earley, RL and Silvestre, F}, title = {DNA methylation in adults and during development of the self-fertilizing mangrove rivulus, Kryptolebias marmoratus.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6016-6033}, pmid = {29988456}, issn = {2045-7758}, abstract = {In addition to genetic variation, epigenetic mechanisms such as DNA methylation might make important contributions to heritable phenotypic diversity in populations. However, it is often difficult to disentangle the contributions of genetic and epigenetic variation to phenotypic diversity. Here, we investigated global DNA methylation and mRNA expression of the methylation-associated enzymes during embryonic development and in adult tissues of one natural isogenic lineage of mangrove rivulus fish, Kryptolebias marmoratus. Being the best-known self-fertilizing hermaphroditic vertebrate affords the opportunity to work with genetically identical individuals to examine, explicitly, the phenotypic effects of epigenetic variance. Using the LUminometric Methylation Assay (LUMA), we described variable global DNA methylation at CpG sites in adult tissues, which differed significantly between hermaphrodite ovotestes and male testes (79.6% and 87.2%, respectively). After fertilization, an immediate decrease in DNA methylation occurred to 15.8% in gastrula followed by re-establishment to 70.0% by stage 26 (liver formation). Compared to zebrafish, at the same embryonic stages, this reprogramming event seems later, deeper, and longer. Furthermore, genes putatively encoding DNA methyltransferases (DNMTs), Ten-Eleven Translocation (TET), and MeCP2 proteins showed specific regulation in adult gonad and brain, and also during early embryogenesis. Their conserved domains and expression profiles suggest that these proteins play important roles during reproduction and development. This study raises questions about mangrove rivulus' peculiar reprogramming period in terms of epigenetic transmission and physiological adaptation of individuals to highly variable environments. In accordance with the general-purpose genotype model, epigenetic mechanisms might allow for the expression of diverse phenotypes among genetically identical individuals. Such phenotypes might help to overcome environmental challenges, making the mangrove rivulus a valuable vertebrate model for ecological epigenetic studies. The mangrove rivulus, Kryptolebias marmoratus, is the best-known self-fertilizing hermaphroditic vertebrate that allows to work with genetically identical individuals to examine, explicitly, the phenotypic effects of epigenetic variance. The reprogramming event is later, more dramatic and longer than in other described vertebrates. High evolutionary conservation and expression patterns of DNMT, TET, and MeCP2 proteins in K. marmoratus suggest biological roles for each member in gametogenesis and development.}, } @article {pmid29988454, year = {2018}, author = {Drummond, FM and Lovegrove, TG and Armstrong, DP}, title = {Combining data-derived priors with postrelease monitoring data to predict persistence of reintroduced populations.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6183-6191}, pmid = {29988454}, issn = {2045-7758}, abstract = {Monitoring is an essential part of reintroduction programs, but many years of data may be needed to obtain reliable population projections. This duration can potentially be reduced by incorporating prior information on expected vital rates (survival and fecundity) when making inferences from monitoring data. The prior distributions for these parameters can be derived from data for previous reintroductions, but it is important to account for site-to-site variation. We evaluated whether such informative priors improved our ability to estimate the finite rate of increase (λ) of the North Island robin (Petroica longipes) population reintroduced to Tawharanui Regional Park, New Zealand. We assessed how precision improved with each year of postrelease data added, comparing models that used informative or uninformative priors. The population grew from about 22 to 80 individuals from 2007 to 2016, with λ estimated to be 1.23 if density dependence was included in the model and 1.13 otherwise. Under either model, 7 years of data were required before the lower 95% credible limit for λ was > 1, giving confidence that the population would persist. The informative priors did not reduce this requirement. Data-derived priors are useful before reintroduction because they allow λ to be estimated in advance. However, in the case examined here, the value of the priors was overwhelmed once site-specific monitoring data became available. The Bayesian method presented is logical for reintroduced populations. It allows prior information (used to inform prerelease decisions) to be integrated with postrelease monitoring. This makes full use of the data for ongoing management decisions. However, if the priors properly account for site-to-site variation, they may have little predictive value compared with the site-specific data. This value will depend on the degree of site-to-site variation as well as the quality of the data.}, } @article {pmid29988453, year = {2018}, author = {McCool, C and Beattie, J and Milford, M and Bakker, JD and Moore, JL and Firn, J}, title = {Automating analysis of vegetation with computer vision: Cover estimates and classification.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6005-6015}, pmid = {29988453}, issn = {2045-7758}, abstract = {This study develops an approach to automating the process of vegetation cover estimates using computer vision and pattern recognition algorithms. Visual cover estimation is a key tool for many ecological studies, yet quadrat-based analyses are known to suffer from issues of consistency between people as well as across sites (spatially) and time (temporally). Previous efforts to estimate cover from photograps require considerable manual work. We demonstrate that an automated system can be used to estimate vegetation cover and the type of vegetation cover present using top-down photographs of 1 m by 1 m quadrats. Vegetation cover is estimated by modelling the distribution of color using a multivariate Gaussian. The type of vegetation cover is then classified, using illumination robust local binary pattern features, into two broad groups: graminoids (grasses) and forbs. This system is evaluated on two datasets from the globally distributed experiment, the Nutrient Network (NutNet). These NutNet sites were selected for analyses because repeat photographs were taken over time and these sites are representative of very different grassland ecosystems-a low stature subalpine grassland in an alpine region of Australia and a higher stature and more productive lowland grassland in the Pacific Northwest of the USA. We find that estimates of treatment effects on grass and forb cover did not differ between field and automated estimates for eight of nine experimental treatments. Conclusions about total vegetation cover did not correspond quite as strongly, particularly at the more productive site. A limitation with this automated system is that the total vegetation cover is given as a percentage of pixels considered to contain vegetation, but ecologists can distinguish species with overlapping coverage and thus can estimate total coverage to exceed 100%. Automated approaches such as this offer techniques for estimating vegetation cover that are repeatable, cheaper to use, and likely more reliable for quantifying changes in vegetation over the long-term. These approaches would also enable ecologists to increase the spatial and temporal depth of their coverage estimates with methods that allow for vegetation sampling over large spatial scales quickly.}, } @article {pmid29988448, year = {2018}, author = {Goodnoe, TT and Hill, JP}, title = {Plasticity of female reproductive resource allocation depends on the presence or absence of prior environmental sex determination in Ceratopteris richardii.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6133-6143}, pmid = {29988448}, issn = {2045-7758}, abstract = {Resource allocation plasticity enables individuals to alter patterns of nutrient use between reproductive and vegetative output to better fit their current environment. In sexually labile plant species, abiotic environmental factors can influence expression of dimorphic gender, resulting in environmental sex determination (ESD), which potentially reduces the need for plasticity of resource allocation by preemptively matching an individual's future nutrient demands to resource availability in its location. Ceratopteris richardii gametophytes exhibit gender-dependent differences in relative carbon and nitrogen content, and ESD in certain nutrient environments. This study examined whether prior ESD in C. richardii gametophyte populations reduced subsequent plasticity of reproductive allocation compared to instances where no ESD occurred, by quantifying phenotypic responses to reduced P, N, or CO 2 availabilities. All three nutrient-limited environments resulted in decreased size of egg-bearing (meristic) gametophytes compared to nonlimited environments, but gametophytes failed to respond to N and CO 2 limitation at the time of sex determination, resulting in no ESD. N limitation resulted in a predictable allometric re-allocation of resources based on small gametophyte size, whereas CO 2 limitation caused a change in reproductive output consistent with true plasticity. Withholding exogenous P caused ESD and had no effect on relative reproductive output of resultant meristic gametophytes because the size decrease was minor. Under P limitation, ESD matched the resource demands of gender phenotypes to their environment before the onset of developmental dimorphism, reducing the need for large allocation adjustments after sex determination.}, } @article {pmid29988446, year = {2018}, author = {Horianopoulos, LC and Boone, CK and Samarasekera, GDNG and Kandola, GK and Murray, BW}, title = {Selection of the sex-linked inhibitor of apoptosis in mountain pine beetle (Dendroctonus ponderosae) driven by enhanced expression during early overwintering.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6253-6264}, pmid = {29988446}, issn = {2045-7758}, abstract = {The mountain pine beetle (Dendroctonus ponderosae) is an insect native to western North America; however, its geographical range has recently expanded north in BC and east into Alberta. To understand the population structure in the areas of expansion, 16 gene-linked microsatellites were screened and compared to neutral microsatellites using outlier analyses of Fst and Fct values. One sex-linked gene, inhibitor of apoptosis (IAP), showed a strong signature of positive selection for neo-X alleles and was analyzed for evidence of adaptive variation. Alleles of IAP were sequenced, and differences between the neo-X and neo-Y alleles were consistent with neutral evolution suggesting that the neo-Y allele may not be under functional constraints. Neo-Y alleles were amplified from gDNA, but not effectively from cDNA, suggesting that there was little IAP expression from neo-Y alleles. There were no differences in overall IAP expression between males and females with the common northern neo-X allele suggesting that the neo-X allele in males compensates for the reduced expression of neo-Y alleles. However, males lacking the most common northern neo-X allele thought to be selected for in northern populations had reduced overall IAP expression in early October-at a time when beetles are preparing for overwintering. This suggests that the most common allele may have more rapid upregulation. The reduced function of neo-Y alleles of IAP suggested by both sequence differences and lower levels of expression may foster a highly selective environment for neo-X alleles such as the common northern allele with more efficient upregulation.}, } @article {pmid29988445, year = {2018}, author = {Harper, LR and Lawson Handley, L and Hahn, C and Boonham, N and Rees, HC and Gough, KC and Lewis, E and Adams, IP and Brotherton, P and Phillips, S and Hänfling, B}, title = {Needle in a haystack? A comparison of eDNA metabarcoding and targeted qPCR for detection of the great crested newt (Triturus cristatus).}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6330-6341}, pmid = {29988445}, issn = {2045-7758}, abstract = {Environmental DNA (eDNA) analysis is a rapid, cost-effective, non-invasive biodiversity monitoring tool which utilises DNA left behind in the environment by organisms for species detection. The method is used as a species-specific survey tool for rare or invasive species across a broad range of ecosystems. Recently, eDNA and "metabarcoding" have been combined to describe whole communities rather than focusing on single target species. However, whether metabarcoding is as sensitive as targeted approaches for rare species detection remains to be evaluated. The great crested newt Triturus cristatus is a flagship pond species of international conservation concern and the first UK species to be routinely monitored using eDNA. We evaluate whether eDNA metabarcoding has comparable sensitivity to targeted real-time quantitative PCR (qPCR) for T. cristatus detection. Extracted eDNA samples (N = 532) were screened for T. cristatus by qPCR and analysed for all vertebrate species using high-throughput sequencing technology. With qPCR and a detection threshold of 1 of 12 positive qPCR replicates, newts were detected in 50% of ponds. Detection decreased to 32% when the threshold was increased to 4 of 12 positive qPCR replicates. With metabarcoding, newts were detected in 34% of ponds without a detection threshold, and in 28% of ponds when a threshold (0.028%) was applied. Therefore, qPCR provided greater detection than metabarcoding but metabarcoding detection with no threshold was equivalent to qPCR with a stringent detection threshold. The proportion of T. cristatus sequences in each sample was positively associated with the number of positive qPCR replicates (qPCR score) suggesting eDNA metabarcoding may be indicative of eDNA concentration. eDNA metabarcoding holds enormous potential for holistic biodiversity assessment and routine freshwater monitoring. We advocate this community approach to freshwater monitoring to guide management and conservation, whereby entire communities can be initially surveyed to best inform use of funding and time for species-specific surveys.}, } @article {pmid29988444, year = {2018}, author = {Wang, R and Zou, J and Meng, J and Wang, J}, title = {Integrative analysis of genome-wide lncRNA and mRNA expression in newly synthesized Brassica hexaploids.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6034-6052}, pmid = {29988444}, issn = {2045-7758}, abstract = {Polyploidization, as a significant evolution force, has been considered to facilitate plant diversity. The expression levels of lncRNAs and how they control the expression of protein-coding genes in allopolyploids remain largely unknown. In this study, lncRNA expression profiles were compared between Brassica hexaploid and its parents using a high-throughput sequencing approach. A total of 2,725, 1,672, and 2,810 lncRNAs were discovered in Brassica rapa, Brassica carinata, and Brassica hexaploid, respectively. It was also discovered that 725 lncRNAs were differentially expressed between Brassica hexaploid and its parents, and 379 lncRNAs were nonadditively expressed in this hexaploid. LncRNAs have multiple expression patterns between Brassica hexaploid and its parents and show paternal parent-biased expression. These lncRNAs were found to implement regulatory functions directly in the long-chain form, and acted as precursors or targets of miRNAs. According to the prediction of the targets of differentially expressed lncRNAs, 109 lncRNAs were annotated, and their target genes were involved in the metabolic process, pigmentation, reproduction, exposure to stimulus, biological regulation, and so on. Compared with the paternal parent, differentially expressed lncRNAs between Brassica hexaploid and its maternal parent participated in more regulation pathways. Additionally, 61 lncRNAs were identified as putative targets of known miRNAs, and 15 other lncRNAs worked as precursors of miRNAs. Some conservative motifs of lncRNAs from different groups were detected, which indicated that these motifs could be responsible for their regulatory roles. Our findings may provide a reference for the further study of the function and action mechanisms of lncRNAs during plant evolution.}, } @article {pmid29988442, year = {2018}, author = {Saltz, JB and Bell, AM and Flint, J and Gomulkiewicz, R and Hughes, KA and Keagy, J}, title = {Why does the magnitude of genotype-by-environment interaction vary?.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6342-6353}, pmid = {29988442}, issn = {2045-7758}, abstract = {Genotype-by-environment interaction (G × E), that is, genetic variation in phenotypic plasticity, is a central concept in ecology and evolutionary biology. G×E has wide-ranging implications for trait development and for understanding how organisms will respond to environmental change. Although G × E has been extensively documented, its presence and magnitude vary dramatically across populations and traits. Despite this, we still know little about why G × E is so evident in some traits and populations, but minimal or absent in others. To encourage synthetic research in this area, we review diverse hypotheses for the underlying biological causes of variation in G × E. We extract common themes from these hypotheses to develop a more synthetic understanding of variation in G × E and suggest some important next steps.}, } @article {pmid29988441, year = {2018}, author = {Fisher, R and Wilson, SK and Sin, TM and Lee, AC and Langlois, TJ}, title = {A simple function for full-subsets multiple regression in ecology with R.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6104-6113}, pmid = {29988441}, issn = {2045-7758}, abstract = {Full-subsets information theoretic approaches are becoming an increasingly popular tool for exploring predictive power and variable importance where a wide range of candidate predictors are being considered. Here, we describe a simple function in the statistical programming language R that can be used to construct, fit, and compare a complete model set of possible ecological or environmental predictors, given a response variable of interest and a starting generalized additive (mixed) model fit. Main advantages include not requiring a complete model to be fit as the starting point for candidate model set construction (meaning that a greater number of predictors can potentially be explored than might be available through functions such as dredge); model sets that include interactions between factors and continuous nonlinear predictors; and automatic removal of models with correlated predictors (based on a user defined criterion for exclusion). The function takes continuous predictors, which are fitted using smoothers via either gam, gamm (mgcv) or gamm4, as well as factor variables which are included on their own or as two-level interaction terms within the gam smooth (via use of the "by" argument), or with themselves. The function allows any model to be constructed and used as a null model, and takes a range of arguments that allow control over the model set being constructed, including specifying cyclic and linear continuous predictors, specification of the smoothing algorithm used, and the maximum complexity allowed for smooth terms. The use of the function is demonstrated via case studies that highlight how appropriate model sets can be easily constructed and the broader utility of the approach for exploratory ecology.}, } @article {pmid29988440, year = {2018}, author = {Sparkman, AM and Clark, AD and Brummett, LJ and Chism, KR and Combrink, LL and Kabey, NM and Schwartz, TS}, title = {Convergence in reduced body size, head size, and blood glucose in three island reptiles.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6169-6182}, pmid = {29988440}, issn = {2045-7758}, abstract = {Many oceanic islands harbor diverse species that differ markedly from their mainland relatives with respect to morphology, behavior, and physiology. A particularly common morphological change exhibited by a wide range of species on islands worldwide involves either a reduction in body size, termed island dwarfism, or an increase in body size, termed island gigantism. While numerous instances of dwarfism and gigantism have been well documented, documentation of other morphological changes on islands remains limited. Furthermore, we lack a basic understanding of the physiological mechanisms that underlie these changes, and whether they are convergent. A major hypothesis for the repeated evolution of dwarfism posits selection for smaller, more efficient body sizes in the context of low resource availability. Under this hypothesis, we would expect the physiological mechanisms known to be downregulated in model organisms exhibiting small body sizes due to dietary restriction or artificial selection would also be downregulated in wild species exhibiting dwarfism on islands. We measured body size, relative head size, and circulating blood glucose in three species of reptiles-two snakes and one lizard-in the California Channel Islands relative to mainland populations. Collating data from 6 years of study, we found that relative to mainland population the island populations had smaller body size (i.e., island dwarfism), smaller head sizes relative to body size, and lower levels of blood glucose, although with some variation by sex and year. These findings suggest that the island populations of these three species have independently evolved convergent physiological changes (lower glucose set point) corresponding to convergent changes in morphology that are consistent with a scenario of reduced resource availability and/or changes in prey size on the islands. This provides a powerful system to further investigate ecological, physiological, and genetic variables to elucidate the mechanisms underlying convergent changes in life history on islands.}, } @article {pmid29988439, year = {2018}, author = {Lin, D and Bi, K and Conroy, CJ and Lacey, EA and Schraiber, JG and Bowie, RCK}, title = {Mito-nuclear discordance across a recent contact zone for California voles.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6226-6241}, pmid = {29988439}, issn = {2045-7758}, abstract = {To examine the processes that maintain genetic diversity among closely related taxa, we investigated the dynamics of introgression across a contact zone between two lineages of California voles (Microtus californicus). We tested the prediction that introgression of nuclear loci would be greater than that for mitochondrial loci, assuming ongoing gene flow across the contact zone. We also predicted that genomic markers would show a mosaic pattern of differentiation across this zone, consistent with genomes that are semi-permeable. Using mitochondrial cytochrome b sequences and genome-wide loci developed via ddRAD-seq, we analyzed genetic variation for 10 vole populations distributed along the central California coast; this transect included populations from within the distributions of both parental lineages as well as the putative contact zone. Our analyses revealed that (1) the two lineages examined are relatively young, having diverged ca. 8.5-54 kya, (2) voles from the contact zone in Santa Barbara County did not include F1 or early generation backcrossed individuals, and (3) there appeared to be little to no recurrent gene flow across the contact zone. Introgression patterns for mitochondrial and nuclear markers were not concordant; only mitochondrial markers revealed evidence of introgression, putatively due to historical hybridization. These differences in genetic signatures are intriguing given that the contact zone occurs in a region of continuous vole habitat, with no evidence of past or present physical barriers. Future studies that examine specific isolating mechanisms, such as microhabitat use and mate choice, will facilitate our understanding of how genetic boundaries are maintained in this system.}, } @article {pmid29988438, year = {2018}, author = {Tipayno, SC and Truu, J and Samaddar, S and Truu, M and Preem, JK and Oopkaup, K and Espenberg, M and Chatterjee, P and Kang, Y and Kim, K and Sa, T}, title = {The bacterial community structure and functional profile in the heavy metal contaminated paddy soils, surrounding a nonferrous smelter in South Korea.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6157-6168}, pmid = {29988438}, issn = {2045-7758}, abstract = {The pollution of agricultural soils by the heavy metals affects the productivity of the land and has an impact on the quality of the surrounding ecosystems. This study investigated the bacterial community structure in the heavy metal contaminated sites along a smelter and a distantly located paddy field to elucidate the factors that are related to the alterations of the bacterial communities under the conditions of heavy metal pollution. Among the study sites, the bacterial communities in the soil did not show any significant differences in their richness and diversity. The soil bacterial communities at the three study sites were distinct from one another at each site, possessing a distinct set of bacterial phylotypes. Among the study sites, significant changes were observed in the abundances of the bacterial phyla and genera. The variations in the bacterial community structure were mostly related to the general soil properties at the phylum level, while at the finer taxonomic levels, the concentrations of arsenic (As) and lead (Pb) were the significant factors, affecting the community structure. The relative abundances of the genera Desulfatibacillum and Desulfovirga were negatively correlated to the concentrations of As, Pb, and cadmium (Cd) in the soil, while the genus Bacillus was positively correlated to the concentrations of As and Cd. According to the results of the prediction of bacterial community functions, the soil bacterial communities of the heavy metal polluted sites were characterized by the more abundant enzymes involved in DNA replication and repair, translation, transcription, and the nucleotide metabolism pathways, while the amino acid and lipid metabolism, as well as the biodegradation potential of xenobiotics, were reduced. Our results showed that the adaptation of the bacterial communities to the heavy metal contamination was predominantly attributed to the replacement process, while the changes in community richness were linked to the variations in the soil pH values.}, } @article {pmid29988436, year = {2018}, author = {Dong, Z and Li, Y and Zhang, Z}, title = {Genetic diversity of melon aphids Aphis gossypii associated with landscape features.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6308-6316}, pmid = {29988436}, issn = {2045-7758}, abstract = {Despite increasing evidence that landscape features strongly influence the abundance and dispersal of insect populations, landscape composition has seldom been explicitly linked to genetic structure. We conducted a genetic study of the melon aphid, Aphis gossypii, in two counties of Beijing, China during spring migration using samples from watermelon. We performed aphid genetic analysis using restriction site associated DNA sequencing (2b-RAD) and investigated the relationship between land cover and the genetic diversity. The percentage area of land cover (cropland, vegetable, orchard, grassland, woodland) was quantified in each particular scale (ranging from 0.5 km to 3 km) and was used as a predictor variable in our generalized linear models. We found a moderate level of genetic differentiation among nine sampled populations. Geographic distance and genetic distance were not significantly associated, indicating that geographic location was not a barrier to migration. These nine populations could be clustered depending on their level of genetic diversity (high and low). The genetic diversity (Shannon's information index) was positively correlated with grassland at the spatial scales of 1 and 2 km and negatively with orchard and vegetable at 0.5 and 1 km. Genetic diversity was best predicted by the grassland + orchard + vegetable model at a spatial scale of 1 km. Based on the method of relative weights, orchard land had the greatest relative importance, followed by grassland and vegetable land, in that order. This study contributes to our understanding of the genetic variation of aphids in agricultural landscapes.}, } @article {pmid29988435, year = {2018}, author = {Fisher, RN and Brehme, CS and Hathaway, SA and Hovey, TE and Warburton, ML and Stokes, DC}, title = {Longevity and population age structure of the arroyo southwestern toad (Anaxyrus californicus) with drought implications.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6124-6132}, pmid = {29988435}, issn = {2045-7758}, abstract = {The arroyo southwestern toad is a specialized and federally endangered amphibian endemic to the coastal plains and mountains of central and southern California and northwestern Baja California. It is largely unknown how long these toads live in natural systems, how their population demographics vary across occupied drainages, and how hydrology affects age structure. We used skeletochronology to estimate the ages of adult arroyo toads in seven occupied drainages with varying surface water hydrology in southern California. We processed 179 adult toads with age estimates between 1 and 6 years. Comparisons between skeletochronological ages and known ages of PIT tagged toads showed that skeletochronology likely underestimated toad age by up to 2 years, indicating they may live to 7 or 8 years, but nonetheless major patterns were evident. Arroyo toads showed sexual size dimorphism with adult females reaching a maximum size of 12 mm greater than males. Population age structure varied among the sites. Age structure at sites with seasonally predictable surface water was biased toward younger individuals, which indicated stable recruitment for these populations. Age structures at the ephemeral sites were biased toward older individuals with cohorts roughly corresponding to higher rainfall years. These populations are driven by surface water availability, a stochastic process, and thus more unstable. Based on our estimates of toad ages, climate predictions of extreme and prolonged drought events could mean that the number of consecutive dry years could surpass the maximum life span of toads making them vulnerable to extirpation, especially in ephemeral freshwater systems. Understanding the relationship between population demographics and hydrology is essential for predicting species resilience to projected changes in weather and rainfall patterns. The arroyo toad serves as a model for understanding potential responses to climatic and hydrologic changes in Mediterranean stream systems. We recommend development of adaptive management strategies to address these threats.}, } @article {pmid29988434, year = {2018}, author = {Bennett, S and Halford, AR and Choat, JH and Hobbs, JA and Santana-Garcon, J and Ayling, AM and Harvey, ES and Newman, SJ}, title = {Geography and island geomorphology shape fish assemblage structure on isolated coral reef systems.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6242-6252}, pmid = {29988434}, issn = {2045-7758}, abstract = {We quantify the relative importance of multi-scale drivers of reef fish assemblage structure on isolated coral reefs at the intersection of the Indian and Indo-Pacific biogeographical provinces. Large (>30 cm), functionally-important and commonly targeted species of fish, were surveyed on the outer reef crest/front at 38 coral reef sites spread across three oceanic coral reef systems (i.e. Christmas Island, Cocos (Keeling) Islands and the Rowley Shoals), in the tropical Indian Ocean (c. 1.126 x 106 km2). The effects of coral cover, exposure, fishing pressure, lagoon size and geographical context, on observed patterns of fish assemblage structure were modelled using Multivariate Regression Trees. Reef fish assemblages were clearly separated in space with geographical location explaining ~53 % of the observed variation. Lagoon size, within each isolated reef system was an equally effective proxy for explaining fish assemblage structure. Among local-scale variables, 'distance from port', a proxy for the influence of fishing, explained 5.2% of total variation and separated the four most isolated reefs from Cocos (Keeling) Island, from reefs with closer boating access. Other factors were not significant. Major divisions in assemblage structure were driven by sister taxa that displayed little geographical overlap between reef systems and low abundances of several species on Christmas Island corresponding to small lagoon habitats. Exclusion of geographical context from the analysis resulted in local processes explaining 47.3% of the variation, highlighting the importance of controlling for spatial correlation to understand the drivers of fish assemblage structure. Our results suggest reef fish assemblage structure on remote coral reef systems in the tropical eastern Indian Ocean reflects a biogeographical legacy of isolation between Indian and Pacific fish faunas and geomorphological variation within the region, more than local fishing pressure or reef condition. Our findings re-emphasise the importance that historical processes play in structuring contemporary biotic communities.}, } @article {pmid29988432, year = {2018}, author = {Banner, KM and Irvine, KM and Rodhouse, TJ and Wright, WJ and Rodriguez, RM and Litt, AR}, title = {Improving geographically extensive acoustic survey designs for modeling species occurrence with imperfect detection and misidentification.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6144-6156}, pmid = {29988432}, issn = {2045-7758}, abstract = {Acoustic recording units (ARUs) enable geographically extensive surveys of sensitive and elusive species. However, a hidden cost of using ARU data for modeling species occupancy is that prohibitive amounts of human verification may be required to correct species identifications made from automated software. Bat acoustic studies exemplify this challenge because large volumes of echolocation calls could be recorded and automatically classified to species. The standard occupancy model requires aggregating verified recordings to construct confirmed detection/non-detection datasets. The multistep data processing workflow is not necessarily transparent nor consistent among studies. We share a workflow diagramming strategy that could provide coherency among practitioners. A false-positive occupancy model is explored that accounts for misclassification errors and enables potential reduction in the number of confirmed detections. Simulations informed by real data were used to evaluate how much confirmation effort could be reduced without sacrificing site occupancy and detection error estimator bias and precision. We found even under a 50% reduction in total confirmation effort, estimator properties were reasonable for our assumed survey design, species-specific parameter values, and desired precision. For transferability, a fully documented r package, OCacoustic, for implementing a false-positive occupancy model is provided. Practitioners can apply OCacoustic to optimize their own study design (required sample sizes, number of visits, and confirmation scenarios) for properly implementing a false-positive occupancy model with bat or other wildlife acoustic data. Additionally, our work highlights the importance of clearly defining research objectives and data processing strategies at the outset to align the study design with desired statistical inferences.}, } @article {pmid29988431, year = {2018}, author = {Fiedler, S and Perring, MP and Tietjen, B}, title = {Integrating trait-based empirical and modeling research to improve ecological restoration.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6369-6380}, pmid = {29988431}, issn = {2045-7758}, abstract = {A global ecological restoration agenda has led to ambitious programs in environmental policy to mitigate declines in biodiversity and ecosystem services. Current restoration programs can incompletely return desired ecosystem service levels, while resilience of restored ecosystems to future threats is unknown. It is therefore essential to advance understanding and better utilize knowledge from ecological literature in restoration approaches. We identified an incomplete linkage between global change ecology, ecosystem function research, and restoration ecology. This gap impedes a full understanding of the interactive effects of changing environmental factors on the long-term provision of ecosystem functions and a quantification of trade-offs and synergies among multiple services. Approaches that account for the effects of multiple changing factors on the composition of plant traits and their direct and indirect impact on the provision of ecosystem functions and services can close this gap. However, studies on this multilayered relationship are currently missing. We therefore propose an integrated restoration agenda complementing trait-based empirical studies with simulation modeling. We introduce an ongoing case study to demonstrate how this framework could allow systematic assessment of the impacts of interacting environmental factors on long-term service provisioning. Our proposed agenda will benefit restoration programs by suggesting plant species compositions with specific traits that maximize the supply of multiple ecosystem services in the long term. Once the suggested compositions have been implemented in actual restoration projects, these assemblages should be monitored to assess whether they are resilient as well as to improve model parameterization. Additionally, the integration of empirical and simulation modeling research can improve global outcomes by raising the awareness of which restoration goals can be achieved, due to the quantification of trade-offs and synergies among ecosystem services under a wide range of environmental conditions.}, } @article {pmid29988430, year = {2018}, author = {Chaise, LL and Prinet, I and Toscani, C and Gallon, SL and Paterson, W and McCafferty, DJ and Théry, M and Ancel, A and Gilbert, C}, title = {Local weather and body condition influence habitat use and movements on land of molting female southern elephant seals (Mirounga leonina).}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6081-6090}, pmid = {29988430}, issn = {2045-7758}, abstract = {Southern elephant seals (Mirounga leonina) are known to move and aggregate while molting, but little is known about their behavior on land during this time. In this study, 60 adult females were monitored (23 with GPS tags) during four molting seasons, between 2012 and 2016 at Kerguelen Archipelago, Indian Ocean. Population surveys were recorded each year (N = 230 daily counts), and habitat use was analyzed in relation to the stage of the molt and local weather. Based on stage of molt, habitat use, and movements on land, we classified the molt of elephant seals into three phases: (1) a "search phase" at the initial stage of molt when grass and wallow habitats were used and characterized by greater mean distances travelled on land per day compared with the two other phases; (2) a "resident phase": during initial and mid-stage of molt when animals were found in grass and wallow habitats but with less distance moved on land; and (3) a "termination phase" at the final stage of molt where grass and beach habitats were occupied with no change in distances. Windchill and solar radiation influenced individual distances moved per day (mean 590 ± 237.0 m) at the mid- and final stage of molt such that animals travelled greater distances on days of low windchill or high solar radiation. Individual variation in distance moved and relative habitat use were also linked to body mass index (BMI) at arrival on the colony, as females with higher BMI moved less and preferred beach habitat. Moreover, the individual rate of molt increased with the use of wallows. Aggregation rate tended to be negatively correlated with distances moved. We therefore suggest that individuals face an energetic trade-off while molting, balancing energy expenditure between movement and thermoregulation.}, } @article {pmid29988428, year = {2018}, author = {Horn, RL and Marques, AJD and Manseau, M and Golding, B and Klütsch, CFC and Abraham, K and Wilson, PJ}, title = {Parallel evolution of site-specific changes in divergent caribou lineages.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6053-6064}, pmid = {29988428}, issn = {2045-7758}, abstract = {The parallel evolution of phenotypes or traits within or between species provides important insight into the basic mechanisms of evolution. Genetic and genomic advances have allowed investigations into the genetic underpinnings of parallel evolution and the independent evolution of similar traits in sympatric species. Parallel evolution may best be exemplified among species where multiple genetic lineages, descended from a common ancestor, colonized analogous environmental niches, and converged on a genotypic or phenotypic trait. Modern North American caribou (Rangifer tarandus) originated from three ancestral sources separated during the Last Glacial Maximum (LGM): the Beringian-Eurasian lineage (BEL), the North American lineage (NAL), and the High Arctic lineage (HAL). Historical introgression between the NAL and the BEL has been found throughout Ontario and eastern Manitoba. In this study, we first characterized the functional differentiation in the cytochrome-b (cytB) gene by identifying nonsynonymous changes. Second, the caribou lineages were used as a direct means to assess site-specific parallel changes among lineages. There was greater functional diversity within the NAL despite the BEL having greater neutral diversity. The patterns of amino acid substitutions occurring within different lineages supported the parallel evolution of cytB amino acid substitutions suggesting different selective pressures among lineages. This study highlights the independent evolution of identical amino acid substitutions within a wide-ranging mammal species that have diversified from different ancestral haplogroups and where ecological niches can invoke parallel evolution.}, } @article {pmid29988427, year = {2018}, author = {Lobo, A and Hansen, OK and Hansen, JK and Erichsen, EO and Jacobsen, B and Kjær, ED}, title = {Local adaptation through genetic differentiation in highly fragmented Tilia cordata populations.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {5968-5976}, pmid = {29988427}, issn = {2045-7758}, abstract = {We assessed the level of geographic differentiation of Tilia cordata in Denmark based on tests of 91 trees selected from 12 isolated populations. We used quantitative analysis of spring phenology and population genetic analysis based on SSR markers to infer the likely historical genetic processes within and among populations. High genetic variation within and among populations was observed in spring phenology, which correlated with spring temperatures at the origin of the tested T. cordata trees. The population genetic analysis revealed significant differentiation among the populations, but with no clear sign of isolation by distance. We infer the findings as indications of ongoing fine scale selection in favor of local growth conditions made possible by limited gene flow among the small and fragmented populations. This hypothesis fits well with reports of limited fruiting in the investigated Danish T. cordata populations, while the species is known for its ability to propagate vegetatively by root suckers. Our results suggest that both divergent selection and genetic drift may have played important roles in forming the genetic patterns of T. cordata at its northern distribution limit. However, we also speculate that epigenetic mechanism arising from the original population environment could have created similar patterns in regulating the spring phenology.}, } @article {pmid29988426, year = {2018}, author = {Peng, Y and Yang, JX and Zhou, XH and Peng, PH and Li, JJ and He, WM}, title = {Warming delays the phenological sequences of an autumn-flowering invader.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6299-6307}, pmid = {29988426}, issn = {2045-7758}, abstract = {Phenology can play an important role in driving plant invasions; however, little is known about how climate warming, nitrogen (N) deposition, and invasion stages influence the phenological sequences of autumn-flowering invaders in a subtropical climate. Accordingly, we conducted an experiment to address the effects of experimental warming, N-addition, and community types on the first inflorescence buds, flowering, seed-setting, and dieback of invasive Solidago canadensis. Warming delayed the onset of first inflorescence buds, flowering, seed-setting, and dieback; N-addition did not influence these four phenophases; community types influenced the onset of first seed-setting but not the other phenological phases. Seed-setting was more sensitive to experimental manipulations than the other phenophases. The onset of first inflorescence buds, flowering, and seed-setting was marginally or significantly correlated with ramet height but not ramet numbers. Our results suggest that future climate warming might delay the phenological sequences of autumn-flowering invaders and some phenophases can shift with invasion stages.}, } @article {pmid29988420, year = {2018}, author = {Harvey, BJ and Nash, KL and Blanchard, JL and Edwards, DP}, title = {Ecosystem-based management of coral reefs under climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6354-6368}, pmid = {29988420}, issn = {2045-7758}, abstract = {Coral reefs provide food and livelihoods for hundreds of millions of people as well as harbour some of the highest regions of biodiversity in the ocean. However, overexploitation, land-use change and other local anthropogenic threats to coral reefs have left many degraded. Additionally, coral reefs are faced with the dual emerging threats of ocean warming and acidification due to rising CO 2 emissions, with dire predictions that they will not survive the century. This review evaluates the impacts of climate change on coral reef organisms, communities and ecosystems, focusing on the interactions between climate change factors and local anthropogenic stressors. It then explores the shortcomings of existing management and the move towards ecosystem-based management and resilience thinking, before highlighting the need for climate change-ready marine protected areas (MPAs), reduction in local anthropogenic stressors, novel approaches such as human-assisted evolution and the importance of sustainable socialecological systems. It concludes that designation of climate change-ready MPAs, integrated with other management strategies involving stakeholders and participation at multiple scales such as marine spatial planning, will be required to maximise coral reef resilience under climate change. However, efforts to reduce carbon emissions are critical if the long-term efficacy of local management actions is to be maintained and coral reefs are to survive.}, } @article {pmid29988419, year = {2018}, author = {Carpenter, JK and Kelly, D and Moltchanova, E and O'Donnell, CFJ}, title = {Introduction of mammalian seed predators and the loss of an endemic flightless bird impair seed dispersal of the New Zealand tree Elaeocarpus dentatus.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {5992-6004}, pmid = {29988419}, issn = {2045-7758}, abstract = {Understanding the mutualistic services provided by species is critical when considering both the consequences of their loss or the benefits of their reintroduction. Like many other Pacific islands, New Zealand seed dispersal networks have been changed by both significant losses of large frugivorous birds and the introduction of invasive mammals. These changes are particularly concerning when important dispersers remain unidentified. We tested the impact of frugivore declines and invasive seed predators on seed dispersal for an endemic tree, hinau Elaeocarpus dentatus, by comparing seed dispersal and predation rates on the mainland of New Zealand with offshore sanctuary islands with higher bird and lower mammal numbers. We used cameras and seed traps to measure predation and dispersal from the ground and canopy, respectively. We found that canopy fruit handling rates (an index of dispersal quantity) were poor even on island sanctuaries (only 14% of seeds captured below parent trees on islands had passed through a bird), which suggests that hinau may be adapted for ground-based dispersal by flightless birds. Ground-based dispersal of hinau was low on the New Zealand mainland compared to sanctuary islands (4% of seeds dispersed on the mainland vs. 76% dispersed on islands), due to low frugivore numbers. A flightless endemic rail (Gallirallus australis) conducted the majority of ground-based fruit removal on islands. Despite being threatened, this rail is controversial in restoration projects because of its predatory impacts on native fauna. Our study demonstrates the importance of testing which species perform important mutualistic services, rather than simply relying on logical assumptions.}, } @article {pmid29988417, year = {2018}, author = {Landy, JA and Travis, J}, title = {Unique maternal and environmental effects on the body morphology of the Least Killifish, Heterandria formosa.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6265-6279}, pmid = {29988417}, issn = {2045-7758}, abstract = {An important step in diagnosing local adaptation is the demonstration that phenotypic variation among populations is at least in part genetically based. To do this, many methods experimentally minimize the environmental effect on the phenotype to elucidate the genetic effect. Minimizing the environmental effect often includes reducing possible environmental maternal effects. However, maternal effects can be an important factor in patterns of local adaptation as well as adaptive plasticity. Here, we report the results of an experiment with males from two populations of the poeciliid fish, Heterandria formosa, designed to examine the relative influence of environmental maternal effects and environmental effects experienced during growth and development on body morphology, and, in addition, whether the balance among those effects is unique to each population. We used a factorial design that varied thermal environment and water chemistry experienced by mothers and thermal environment and water chemistry experienced by offspring. We found substantial differences between the two populations in their maternal and offspring norms of reaction of male body morphology to differences in thermal environment and water chemistry. We also found that the balance between maternal effects and postparturition environmental effects differed from one thermal regime to another and among traits. These results indicate that environmental maternal effects can be decidedly population-specific and, as a result, might either contribute to the appearance of or blur evidence for local adaptation. These results also suggest that local adaptation might also occur through the evolution of maternal norms of reaction to important, and varying, environmental factors.}, } @article {pmid29988414, year = {2018}, author = {Si, Y and Xu, Y and Xu, F and Li, X and Zhang, W and Wielstra, B and Wei, J and Liu, G and Luo, H and Takekawa, J and Balachandran, S and Zhang, T and de Boer, WF and Prins, HHT and Gong, P}, title = {Spring migration patterns, habitat use, and stopover site protection status for two declining waterfowl species wintering in China as revealed by satellite tracking.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6280-6289}, pmid = {29988414}, issn = {2045-7758}, abstract = {East Asian migratory waterfowl have greatly declined since the 1950s, especially the populations that winter in China. Conservation is severely hampered by the lack of primary information about migration patterns and stopover sites. This study utilizes satellite tracking techniques and advanced spatial analyses to investigate spring migration of the greater white-fronted goose (Anser albifrons) and tundra bean goose (Anser serrirostris) wintering along the Yangtze River Floodplain. Based on 24 tracks obtained from 21 individuals during the spring of 2015 and 2016, we found that the Northeast China Plain is far-out the most intensively used stopover site during migration, with geese staying for over 1 month. This region has also been intensely developed for agriculture, suggesting a causal link to the decline in East Asian waterfowl wintering in China. The protection of waterbodies used as roosting area, especially those surrounded by intensive foraging land, is critical for waterfowl survival. Over 90% of the core area used during spring migration is not protected. We suggest that future ground surveys should target these areas to confirm their relevance for migratory waterfowl at the population level, and core roosting area at critical spring-staging sites should be integrated in the network of protected areas along the flyway. Moreover, the potential bird-human conflict in core stopover area needs to be further studied. Our study illustrates how satellite tracking combined with spatial analyses can provide crucial insights necessary to improve the conservation of declining Migratory species.}, } @article {pmid29988411, year = {2018}, author = {Gomez-Uchida, D and Cañas-Rojas, D and Riva-Rossi, CM and Ciancio, JE and Pascual, MA and Ernst, B and Aedo, E and Musleh, SS and Valenzuela-Aguayo, F and Quinn, TP and Seeb, JE and Seeb, LW}, title = {Genetic signals of artificial and natural dispersal linked to colonization of South America by non-native Chinook salmon (Oncorhynchus tshawytscha).}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6192-6209}, pmid = {29988411}, issn = {2045-7758}, abstract = {Genetics data have provided unprecedented insights into evolutionary aspects of colonization by non-native populations. Yet, our understanding of how artificial (human-mediated) and natural dispersal pathways of non-native individuals influence genetic metrics, evolution of genetic structure, and admixture remains elusive. We capitalize on the widespread colonization of Chinook salmon Oncorhynchus tshawytscha in South America, mediated by both dispersal pathways, to address these issues using data from a panel of polymorphic SNPs. First, genetic diversity and the number of effective breeders (Nb) were higher among artificial than natural populations. Contemporary gene flow was common between adjacent artificial and natural and adjacent natural populations, but uncommon between geographically distant populations. Second, genetic structure revealed four distinct clusters throughout the Chinook salmon distributional range with varying levels of genetic connectivity. Isolation by distance resulted from weak differentiation between adjacent artificial and natural and between natural populations, with strong differentiation between distant Pacific Ocean and Atlantic Ocean populations, which experienced strong genetic drift. Third, genetic mixture analyses revealed the presence of at least six donor geographic regions from North America, some of which likely hybridized as a result of multiple introductions. Relative propagule pressure or the proportion of Chinook salmon propagules introduced from various geographic regions according to government records significantly influenced genetic mixtures for two of three artificial populations. Our findings support a model of colonization in which high-diversity artificial populations established first; some of these populations exhibited significant admixture resulting from propagule pressure. Low-diversity natural populations were likely subsequently founded from a reduced number of individuals.}, } @article {pmid29988407, year = {2018}, author = {Guillaumot, C and Fabri-Ruiz, S and Martin, A and Eléaume, M and Danis, B and Féral, JP and Saucède, T}, title = {Benthic species of the Kerguelen Plateau show contrasting distribution shifts in response to environmental changes.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6210-6225}, pmid = {29988407}, issn = {2045-7758}, abstract = {Marine life of the Southern Ocean has been facing environmental changes and the direct impact of human activities during the past decades. Benthic communities have particularly been affected by such changes although we only slowly understand the effect of environmental changes on species physiology, biogeography, and distribution. Species distribution models (SDM) can help explore species geographic responses to main environmental changes. In this work, we modeled the distribution of four echinoid species with contrasting ecological niches. Models developed for [2005-2012] were projected to different time periods, and the magnitude of distribution range shifts was assessed for recent-past conditions [1955-1974] and for the future, under scenario RCP 8.5 for [2050-2099]. Our results suggest that species distribution shifts are expected to be more important in a near future compared to the past. The geographic response of species may vary between poleward shift, latitudinal reduction, and local extinction. Species with broad ecological niches and not limited by biogeographic barriers would be the least affected by environmental changes, in contrast to endemic species, restricted to coastal areas, which are predicted to be more sensitive.}, } @article {pmid29988406, year = {2018}, author = {Halczok, TK and Brändel, SD and Flores, V and Puechmaille, SJ and Tschapka, M and Page, RA and Kerth, G}, title = {Male-biased dispersal and the potential impact of human-induced habitat modifications on the Neotropical bat Trachops cirrhosus.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6065-6080}, pmid = {29988406}, issn = {2045-7758}, abstract = {Gene flow, maintained through natal dispersal and subsequent mating events, is one of the most important processes in both ecology and population genetics. Among mammalian populations, gene flow is strongly affected by a variety of factors, including the species' ability to disperse, and the composition of the environment which can limit dispersal. Information on dispersal patterns is thus crucial both for conservation management and for understanding the social system of a species. We used 16 polymorphic nuclear microsatellite loci in addition to mitochondrial DNA sequences (1.61 kbp) to analyse the population structure and the sex-specific pattern of natal dispersal in the frog-eating fringe-lipped bat, Trachops cirrhosus, in Central Panama. Our study revealed that-unlike most of the few other investigated Neotropical bats-gene flow in this species is mostly male-mediated. Nevertheless, distinct genetic clusters occur in both sexes. In particular, the presence of genetic differentiation in the dataset only consisting of the dispersing sex (males) indicates that gene flow is impeded within our study area. Our data are in line with the Panama Canal in connection with the widening of the Río Chagres during the canal construction acting as a recent barrier to gene flow. The sensitivity of T. cirrhosus to human-induced habitat modifications is further indicated by an extremely low capture success in highly fragmented areas. Taken together, our genetic and capture data provide evidence for this species to be classified as less mobile and thus vulnerable to habitat change, information that is important for conservation management.}, } @article {pmid29988405, year = {2018}, author = {Sanchez, JL and Trexler, JC}, title = {When is an herbivore not an herbivore? Detritivory facilitates herbivory in a freshwater system.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {5977-5991}, pmid = {29988405}, issn = {2045-7758}, abstract = {Herbivory is thought to be an inefficient diet, but it independently evolved from carnivorous ancestors in many metazoan groups, suggesting that plant-eating is adaptive in some circumstances. In this study, we tested two hypotheses to explain the adaptive evolution of herbivory: (i) the Heterotroph Facilitation hypothesis (herbivory is adaptive because herbivores supplement their diets with heterotrophic microbes); and (ii) the Lipid Allocation hypothesis (herbivory is adaptive because algae, which have high lipid concentrations, are nutritionally similar to carnivory). We tested these hypotheses using enclosure cages placed in the Everglades and stocked with Sailfin Mollies (Poecilia latipinna), a native herbivore. Using shading and phosphorus addition (P), we manipulated the heterotrophic microbe and lipid composition of colonizing epiphyton and examined the effects of varying food quality on Sailfin Molly life history. Epiphyton grown in "shade only" conditions had a 55% increase in bacterial fatty acids and 34% lower ratios of saturated + monounsaturated to polyunsaturated fatty acids relative to the other treatments. Ratio of autotroph to heterotroph biovolume varied throughout the experiment, with a 697% increase at 3 weeks and 98% decrease at 6 weeks compared to the other treatments. Gut contents revealed that fish fed selectively on epiphyton to compensate for apparent deficiencies in the available food. Fish raised in "shade only" cages experienced the highest survival, which was best explained by autotrophic biovolume and algal- and bacterial-derived fatty acids at 3 weeks (2-6× more likely than alternative models with ∆AICc > 2.00), and by percentage of bacterial fatty acids in the diet at 6 weeks (3-8× more likely than alternative models with ∆AICc > 2.00). There were no differences in fish growth among treatments. Autotrophic lipids play a role in early fish life history, but we did not find these to be the best predictors of life history later in the juvenile period. Instead, heterotrophic lipids facilitated the herbivorous diet and enhanced survival of juvenile fish in our experiment. Bacterial fatty acid content of the diet promoted herbivore survival, consistent with the Heterotroph Facilitation hypothesis. This is the first study to explicitly contrast Heterotrophic Facilitation and Lipid Allocation hypotheses for the adaptive evolution of herbivory in an aquatic system.}, } @article {pmid29988352, year = {2018}, author = {Xu, H and Cao, M and Wang, Z and Wu, Y and Cao, Y and Wu, J and Le, Z and Cui, P and Ding, H and Xu, W and Peng, H and Jiang, J and Wu, Y and Jiang, X and Zhang, Z and Rao, D and Li, J and Lei, F and Xia, N and Han, L and Cao, W and Wu, J and Xia, X and Li, Y}, title = {Low ecological representation in the protected area network of China.}, journal = {Ecology and evolution}, volume = {8}, number = {12}, pages = {6290-6298}, pmid = {29988352}, issn = {2045-7758}, abstract = {Protected areas are considered as an essential strategy to halt the decline of biodiversity. Ecological representation in protected areas is crucial for assessment on the progress toward conservation targets. Although China has established a large number of protected areas since the 1950s, ecological representation of protected areas is poorly understood. Here, we performed the complementarity analysis to evaluate ecological representation of protected areas in China. We used a database of the geographical distribution for 10,396 woody plant species, 2,305 fern species, 406 amphibian species, 460 reptile species, 1,364 bird species, and 590 mammal species from 2,376 counties across China. We identified complementary sets of counties for all species or threatened species of plant and vertebrate species using a complementarity algorithm. We evaluated ecological representation of 3,627 protected areas and discerned conservation gaps by comparing the distribution of protected areas with complementary sets. The results show that the spatially representative and complementary sites for biodiversity are poorly covered, and a fairly large proportion of protected areas is not designed to efficiently represent biodiversity at the national scale. Our methodology can serve as a generic framework for assessment on ecological representation of protected areas at the national scale.}, } @article {pmid29988312, year = {2018}, author = {Qiu, J and Game, ET and Tallis, H and Olander, LP and Glew, L and Kagan, JS and Kalies, EL and Michanowicz, D and Phelan, J and Polasky, S and Reed, J and Sills, EO and Urban, D and Weaver, SK}, title = {Evidence-Based Causal Chains for Linking Health, Development, and Conservation Actions.}, journal = {Bioscience}, volume = {68}, number = {3}, pages = {182-193}, pmid = {29988312}, issn = {0006-3568}, abstract = {Sustainability challenges for nature and people are complex and interconnected, such that effective solutions require approaches and a common theory of change that bridge disparate disciplines and sectors. Causal chains offer promising approaches to achieving an integrated understanding of how actions affect ecosystems, the goods and services they provide, and ultimately, human well-being. Although causal chains and their variants are common tools across disciplines, their use remains highly inconsistent, limiting their ability to support and create a shared evidence base for joint actions. In this article, we present the foundational concepts and guidance of causal chains linking disciplines and sectors that do not often intersect to elucidate the effects of actions on ecosystems and society. We further discuss considerations for establishing and implementing causal chains, including nonlinearity, trade-offs and synergies, heterogeneity, scale, and confounding factors. Finally, we highlight the science, practice, and policy implications of causal chains to address real-world linked human-nature challenges.}, } @article {pmid29988169, year = {2018}, author = {Apaldetti, C and Martínez, RN and Cerda, IA and Pol, D and Alcober, O}, title = {An early trend towards gigantism in Triassic sauropodomorph dinosaurs.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1227-1232}, doi = {10.1038/s41559-018-0599-y}, pmid = {29988169}, issn = {2397-334X}, abstract = {Dinosaurs dominated the terrestrial ecosystems for more than 140 Myr during the Mesozoic era, and among them were sauropodomorphs, the largest land animals recorded in the history of life. Early sauropodomorphs were small bipeds, and it was long believed that acquisition of giant body size in this clade (over 10 tonnes) occurred during the Jurassic and was linked to numerous skeletal modifications present in Eusauropoda. Although the origin of gigantism in sauropodomorphs was a pivotal stage in the history of dinosaurs, an incomplete fossil record obscures details of this crucial evolutionary change. Here, we describe a new sauropodomorph from the Late Triassic of Argentina nested within a clade of other non-eusauropods from southwest Pangaea. Members of this clade attained large body size while maintaining a plesiomorphic cyclical growth pattern, displaying many features of the body plan of basal sauropodomorphs and lacking most anatomical traits previously regarded as adaptations to gigantism. This novel strategy highlights a highly accelerated growth rate, an improved avian-style respiratory system, and modifications of the vertebral epaxial musculature and hindlimbs as critical to the evolution of gigantism. This reveals that the first pulse towards gigantism in dinosaurs occurred over 30 Myr before the appearance of the first eusauropods.}, } @article {pmid29988168, year = {2018}, author = {Ferreira, CM and Nagelkerken, I and Goldenberg, SU and Connell, SD}, title = {CO2 emissions boost the benefits of crop production by farming damselfish.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1223-1226}, doi = {10.1038/s41559-018-0607-2}, pmid = {29988168}, issn = {2397-334X}, abstract = {Farming is a technique employed by both humans and animals to enhance crop yields, allowing their populations to increase beyond the natural carrying capacity of the environment. Using volcanic CO2 vents, we investigate how a species of herbivorous fish (the black scalyfin Parma alboscapularis) may use increasing anthropogenic CO2 emissions to enhance its crop yields. We found that these farming fish can take advantage of this resource enrichment, to grow crops within smaller territories and increase the capacity of the environment to support more densely packed fish populations.}, } @article {pmid29988167, year = {2018}, author = {Serván, CA and Capitán, JA and Grilli, J and Morrison, KE and Allesina, S}, title = {Coexistence of many species in random ecosystems.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1237-1242}, doi = {10.1038/s41559-018-0603-6}, pmid = {29988167}, issn = {2397-334X}, abstract = {Rich ecosystems harbour thousands of species interacting in tangled networks encompassing predation, mutualism and competition. Such widespread biodiversity is puzzling, because in ecological models it is exceedingly improbable for large communities to stably coexist. One aspect rarely considered in these models, however, is that coexisting species in natural communities are a selected portion of a much larger pool, which has been pruned by population dynamics. Here we compute the distribution of the number of species that can coexist when we start from a pool of species interacting randomly, and show that even in this case we can observe rich, stable communities. Interestingly, our results show that, once stability conditions are met, network structure has very little influence on the level of biodiversity attained. Our results identify the main drivers responsible for widespread coexistence in natural communities, providing a baseline for determining which structural aspects of empirical communities promote or hinder coexistence.}, } @article {pmid29988166, year = {2018}, author = {Mysterud, A and Rolandsen, CM}, title = {A reindeer cull to prevent chronic wasting disease in Europe.}, journal = {Nature ecology & evolution}, volume = {2}, number = {9}, pages = {1343-1345}, doi = {10.1038/s41559-018-0616-1}, pmid = {29988166}, issn = {2397-334X}, } @article {pmid29988165, year = {2018}, author = {Niehus, R and Mitri, S}, title = {Handling unpredictable ecosystems.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1207-1208}, doi = {10.1038/s41559-018-0619-y}, pmid = {29988165}, issn = {2397-334X}, } @article {pmid29988164, year = {2018}, author = {Morales, HE and Pavlova, A and Amos, N and Major, R and Kilian, A and Greening, C and Sunnucks, P}, title = {Concordant divergence of mitogenomes and a mitonuclear gene cluster in bird lineages inhabiting different climates.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1258-1267}, doi = {10.1038/s41559-018-0606-3}, pmid = {29988164}, issn = {2397-334X}, abstract = {Metabolic processes in eukaryotic cells depend on interactions between mitochondrial and nuclear gene products (mitonuclear interactions). These interactions could have a direct role in population divergence. Here, we study mitonuclear co-evolution in a widespread bird that experienced population divergence followed by bidirectional mitochondrial introgression into different nuclear backgrounds. Using >60,000 single nucleotide polymorphisms, we quantify patterns of nuclear genetic differentiation between populations that occupy areas with different climates and harbour deeply divergent mitochondrial lineages despite ongoing nuclear gene flow. We find that strong genetic differentiation and sequence divergence in a region of ~15.4 megabases on chromosome 1A mirror the geographic pattern of mitochondrial DNA divergence. This result is seen in two different transects representing populations with different nuclear backgrounds. The chromosome 1A region is enriched for genes performing mitochondrial functions (N-mt genes). Molecular signatures of selective sweeps in this region alongside those in the mitochondrial genome suggest a history of adaptive mitonuclear co-introgression. Moreover, evidence for large linkage disequilibrium blocks in this genomic region suggests that low recombination could facilitate functional interactions between co-evolved nuclear alleles. Our results are consistent with mitonuclear co-evolution as an important mechanism for population divergence and local adaptation.}, } @article {pmid29988163, year = {2018}, author = {Wang, S}, title = {Simplicity from complex interactions.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1201-1202}, doi = {10.1038/s41559-018-0618-z}, pmid = {29988163}, issn = {2397-334X}, } @article {pmid29988162, year = {2018}, author = {Beardmore, RE and Cook, E and Nilsson, S and Smith, AR and Tillmann, A and Esquivel, BD and Haynes, K and Gow, NAR and Brown, AJP and White, TC and Gudelj, I}, title = {Drug-mediated metabolic tipping between antibiotic resistant states in a mixed-species community.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1312-1320}, doi = {10.1038/s41559-018-0582-7}, pmid = {29988162}, issn = {2397-334X}, abstract = {Microbes rarely exist in isolation, rather, they form intricate multi-species communities that colonize our bodies and inserted medical devices. However, the efficacy of antimicrobials is measured in clinical laboratories exclusively using microbial monocultures. Here, to determine how multi-species interactions mediate selection for resistance during antibiotic treatment, particularly following drug withdrawal, we study a laboratory community consisting of two microbial pathogens. Single-species dose responses are a poor predictor of community dynamics during treatment so, to better understand those dynamics, we introduce the concept of a dose-response mosaic, a multi-dimensional map that indicates how species' abundance is affected by changes in abiotic conditions. We study the dose-response mosaic of a two-species community with a 'Gene × Gene × Environment × Environment' ecological interaction whereby Candida glabrata, which is resistant to the antifungal drug fluconazole, competes for survival with Candida albicans, which is susceptible to fluconazole. The mosaic comprises several zones that delineate abiotic conditions where each species dominates. Zones are separated by loci of bifurcations and tipping points that identify what environmental changes can trigger the loss of either species. Observations of the laboratory communities corroborated theory, showing that changes in both antibiotic concentration and nutrient availability can push populations beyond tipping points, thus creating irreversible shifts in community composition from drug-sensitive to drug-resistant species. This has an important consequence: resistant species can increase in frequency even if an antibiotic is withdrawn because, unwittingly, a tipping point was passed during treatment.}, } @article {pmid29988161, year = {2018}, author = {Levis, NA and Isdaner, AJ and Pfennig, DW}, title = {Morphological novelty emerges from pre-existing phenotypic plasticity.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1289-1297}, doi = {10.1038/s41559-018-0601-8}, pmid = {29988161}, issn = {2397-334X}, abstract = {Plasticity-first evolution (PFE) posits that novel features arise when selection refines pre-existing phenotypic plasticity into an adaptive phenotype. However, PFE is controversial because few tests have been conducted in natural populations. Here we present evidence that PFE fostered the origin of an evolutionary novelty that allowed certain amphibians to invade a new niche-a distinctive carnivore morph. We compared morphology, gene expression and growth of three species of spadefoot toad tadpoles when reared on alternative diets: Scaphiopus holbrookii, which (like most frogs) never produce carnivores; Spea multiplicata, which sometimes produce carnivores, but only through diet-induced plasticity; and Spea bombifrons, which often produce carnivores regardless of diet. Consistent with PFE, we found diet-induced plasticity-in morphology and gene expression-in Sc. holbrookii, adaptive refinement of this plasticity in Sp. multiplicata, and further refinement of the carnivore phenotype in Sp. bombifrons. Generally, phenotypic plasticity might play a significant, if underappreciated, role in evolutionary innovation.}, } @article {pmid29988160, year = {2018}, author = {Hui, JHL}, title = {Copepod incompatibilities.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1203-1204}, doi = {10.1038/s41559-018-0615-2}, pmid = {29988160}, issn = {2397-334X}, } @article {pmid29988159, year = {2018}, author = {Stein, LR and Bukhari, SA and Bell, AM}, title = {Personal and transgenerational cues are nonadditive at the phenotypic and molecular level.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1306-1311}, pmid = {29988159}, issn = {2397-334X}, support = {R01 GM082937/GM/NIGMS NIH HHS/United States ; }, abstract = {Organisms can gain information about their environment from their ancestors, their parents or their own personal experience. 'Cue integration' models often start with the simplifying assumption that information from different sources is additive. Here, we test key assumptions and predictions of cue integration theory at both the phenotypic and molecular level in threespined sticklebacks (Gasterosteus aculeatus). We show that regardless of whether cues about predation risk were provided by their father or acquired through personal experience, sticklebacks produced the same set of predator-adapted phenotypes. Moreover, there were nonadditive effects of personal and paternal experience: animals that received cues from both sources resembled animals that received cues from a single source. A similar pattern was detected at the molecular level: there was a core set of genes that were differentially expressed in the brains of offspring regardless of whether risk was experienced by their father, themselves or both. These results provide strong support for cue integration theory because they show that cues provided by parents and personal experience are comparable at both the phenotypic and molecular level, and draw attention to the importance of nonadditive responses to multiple cues.}, } @article {pmid29988158, year = {2018}, author = {Barreto, FS and Watson, ET and Lima, TG and Willett, CS and Edmands, S and Li, W and Burton, RS}, title = {Genomic signatures of mitonuclear coevolution across populations of Tigriopus californicus.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1250-1257}, doi = {10.1038/s41559-018-0588-1}, pmid = {29988158}, issn = {2397-334X}, abstract = {The copepod Tigriopus californicus shows extensive population divergence and is becoming a model for understanding allopatric differentiation and the early stages of speciation. Here, we report a high-quality reference genome for one population (~190 megabases across 12 scaffolds, and ~15,500 protein-coding genes). Comparison with other arthropods reveals 2,526 genes presumed to be specific to T. californicus, with an apparent proliferation of genes involved in ion transport and receptor activity. Beyond the reference population, we report re-sequenced genomes of seven additional populations, spanning the continuum of reproductive isolation. Populations show extreme mitochondrial DNA divergence, with higher levels of amino acid differentiation than observed in other taxa. Across the nuclear genome, we find elevated protein evolutionary rates and positive selection in genes predicted to interact with mitochondrial DNA and the proteins and RNA it encodes in multiple pathways. Together, these results support the hypothesis that rapid mitochondrial evolution drives compensatory nuclear evolution within isolated populations, thereby providing a potentially important mechanism for causing intrinsic reproductive isolation.}, } @article {pmid29988157, year = {2018}, author = {Snell-Rood, EC}, title = {Information integration.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1205-1206}, doi = {10.1038/s41559-018-0578-3}, pmid = {29988157}, issn = {2397-334X}, } @article {pmid29988156, year = {2018}, author = {Jones, KE and Purvis, A}, title = {Ben Collen (1978-2018).}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1199-1200}, doi = {10.1038/s41559-018-0621-4}, pmid = {29988156}, issn = {2397-334X}, } @article {pmid29988122, year = {2018}, author = {Gate, RE and Cheng, CS and Aiden, AP and Siba, A and Tabaka, M and Lituiev, D and Machol, I and Gordon, MG and Subramaniam, M and Shamim, M and Hougen, KL and Wortman, I and Huang, SC and Durand, NC and Feng, T and De Jager, PL and Chang, HY and Aiden, EL and Benoist, C and Beer, MA and Ye, CJ and Regev, A}, title = {Genetic determinants of co-accessible chromatin regions in activated T cells across humans.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1140-1150}, pmid = {29988122}, issn = {1546-1718}, support = {U01 HG009380/HG/NHGRI NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; F32 CA168253/CA/NCI NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 AR071522/AR/NIAMS NIH HHS/United States ; F32 DK096822/DK/NIDDK NIH HHS/United States ; R01 HG007348/HG/NHGRI NIH HHS/United States ; }, abstract = {Over 90% of genetic variants associated with complex human traits map to non-coding regions, but little is understood about how they modulate gene regulation in health and disease. One possible mechanism is that genetic variants affect the activity of one or more cis-regulatory elements leading to gene expression variation in specific cell types. To identify such cases, we analyzed ATAC-seq and RNA-seq profiles from stimulated primary CD4+ T cells in up to 105 healthy donors. We found that regions of accessible chromatin (ATAC-peaks) are co-accessible at kilobase and megabase resolution, consistent with the three-dimensional chromatin organization measured by in situ Hi-C in T cells. Fifteen percent of genetic variants located within ATAC-peaks affected the accessibility of the corresponding peak (local-ATAC-QTLs). Local-ATAC-QTLs have the largest effects on co-accessible peaks, are associated with gene expression and are enriched for autoimmune disease variants. Our results provide insights into how natural genetic variants modulate cis-regulatory elements, in isolation or in concert, to influence gene expression.}, } @article {pmid29988121, year = {2018}, author = {Allahyar, A and Vermeulen, C and Bouwman, BAM and Krijger, PHL and Verstegen, MJAM and Geeven, G and van Kranenburg, M and Pieterse, M and Straver, R and Haarhuis, JHI and Jalink, K and Teunissen, H and Renkens, IJ and Kloosterman, WP and Rowland, BD and de Wit, E and de Ridder, J and de Laat, W}, title = {Enhancer hubs and loop collisions identified from single-allele topologies.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1151-1160}, doi = {10.1038/s41588-018-0161-5}, pmid = {29988121}, issn = {1546-1718}, abstract = {Chromatin folding contributes to the regulation of genomic processes such as gene activity. Existing conformation capture methods characterize genome topology through analysis of pairwise chromatin contacts in populations of cells but cannot discern whether individual interactions occur simultaneously or competitively. Here we present multi-contact 4C (MC-4C), which applies Nanopore sequencing to study multi-way DNA conformations of individual alleles. MC-4C distinguishes cooperative from random and competing interactions and identifies previously missed structures in subpopulations of cells. We show that individual elements of the β-globin superenhancer can aggregate into an enhancer hub that can simultaneously accommodate two genes. Neighboring chromatin domain loops can form rosette-like structures through collision of their CTCF-bound anchors, as seen most prominently in cells lacking the cohesin-unloading factor WAPL. Here, massive collision of CTCF-anchored chromatin loops is believed to reflect 'cohesin traffic jams'. Single-allele topology studies thus help us understand the mechanisms underlying genome folding and functioning.}, } @article {pmid29988082, year = {2018}, author = {Abelson, S and Collord, G and Ng, SWK and Weissbrod, O and Mendelson Cohen, N and Niemeyer, E and Barda, N and Zuzarte, PC and Heisler, L and Sundaravadanam, Y and Luben, R and Hayat, S and Wang, TT and Zhao, Z and Cirlan, I and Pugh, TJ and Soave, D and Ng, K and Latimer, C and Hardy, C and Raine, K and Jones, D and Hoult, D and Britten, A and McPherson, JD and Johansson, M and Mbabaali, F and Eagles, J and Miller, JK and Pasternack, D and Timms, L and Krzyzanowski, P and Awadalla, P and Costa, R and Segal, E and Bratman, SV and Beer, P and Behjati, S and Martincorena, I and Wang, JCY and Bowles, KM and Quirós, JR and Karakatsani, A and La Vecchia, C and Trichopoulou, A and Salamanca-Fernández, E and Huerta, JM and Barricarte, A and Travis, RC and Tumino, R and Masala, G and Boeing, H and Panico, S and Kaaks, R and Krämer, A and Sieri, S and Riboli, E and Vineis, P and Foll, M and McKay, J and Polidoro, S and Sala, N and Khaw, KT and Vermeulen, R and Campbell, PJ and Papaemmanuil, E and Minden, MD and Tanay, A and Balicer, RD and Wareham, NJ and Gerstung, M and Dick, JE and Brennan, P and Vassiliou, GS and Shlush, LI}, title = {Prediction of acute myeloid leukaemia risk in healthy individuals.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {400-404}, doi = {10.1038/s41586-018-0317-6}, pmid = {29988082}, issn = {1476-4687}, support = {MC_UU_12015/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, abstract = {The incidence of acute myeloid leukaemia (AML) increases with age and mortality exceeds 90% when diagnosed after age 65. Most cases arise without any detectable early symptoms and patients usually present with the acute complications of bone marrow failure1. The onset of such de novo AML cases is typically preceded by the accumulation of somatic mutations in preleukaemic haematopoietic stem and progenitor cells (HSPCs) that undergo clonal expansion2,3. However, recurrent AML mutations also accumulate in HSPCs during ageing of healthy individuals who do not develop AML, a phenomenon referred to as age-related clonal haematopoiesis (ARCH)4-8. Here we use deep sequencing to analyse genes that are recurrently mutated in AML to distinguish between individuals who have a high risk of developing AML and those with benign ARCH. We analysed peripheral blood cells from 95 individuals that were obtained on average 6.3 years before AML diagnosis (pre-AML group), together with 414 unselected age- and gender-matched individuals (control group). Pre-AML cases were distinct from controls and had more mutations per sample, higher variant allele frequencies, indicating greater clonal expansion, and showed enrichment of mutations in specific genes. Genetic parameters were used to derive a model that accurately predicted AML-free survival; this model was validated in an independent cohort of 29 pre-AML cases and 262 controls. Because AML is rare, we also developed an AML predictive model using a large electronic health record database that identified individuals at greater risk. Collectively our findings provide proof-of-concept that it is possible to discriminate ARCH from pre-AML many years before malignant transformation. This could in future enable earlier detection and monitoring, and may help to inform intervention.}, } @article {pmid29988081, year = {2018}, author = {Caley, T and Extier, T and Collins, JA and Schefuß, E and Dupont, L and Malaizé, B and Rossignol, L and Souron, A and McClymont, EL and Jimenez-Espejo, FJ and García-Comas, C and Eynaud, F and Martinez, P and Roche, DM and Jorry, SJ and Charlier, K and Wary, M and Gourves, PY and Billy, I and Giraudeau, J}, title = {A two-million-year-long hydroclimatic context for hominin evolution in southeastern Africa.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {76-79}, doi = {10.1038/s41586-018-0309-6}, pmid = {29988081}, issn = {1476-4687}, mesh = {Alkanes/analysis/chemistry ; Animals ; *Biological Evolution ; *Climate ; Extinction, Biological ; Foraminifera/chemistry ; Forests ; History, Ancient ; *Hominidae ; Hydrology ; Indian Ocean ; Lakes ; Malawi ; Plants/chemistry ; *Rain ; Rivers ; Water Cycle ; Waxes/chemistry ; Wetlands ; }, abstract = {The past two million years of eastern African climate variability is currently poorly constrained, despite interest in understanding its assumed role in early human evolution1-4. Rare palaeoclimate records from northeastern Africa suggest progressively drier conditions2,5 or a stable hydroclimate6. By contrast, records from Lake Malawi in tropical southeastern Africa reveal a trend of a progressively wetter climate over the past 1.3 million years7,8. The climatic forcings that controlled these past hydrological changes are also a matter of debate. Some studies suggest a dominant local insolation forcing on hydrological changes9-11, whereas others infer a potential influence of sea surface temperature changes in the Indian Ocean8,12,13. Here we show that the hydroclimate in southeastern Africa (20-25° S) is controlled by interplay between low-latitude insolation forcing (precession and eccentricity) and changes in ice volume at high latitudes. Our results are based on a multiple-proxy reconstruction of hydrological changes in the Limpopo River catchment, combined with a reconstruction of sea surface temperature in the southwestern Indian Ocean for the past 2.14 million years. We find a long-term aridification in the Limpopo catchment between around 1 and 0.6 million years ago, opposite to the hydroclimatic evolution suggested by records from Lake Malawi. Our results, together with evidence of wetting at Lake Malawi, imply that the rainbelt contracted toward the Equator in response to increased ice volume at high latitudes. By reducing the extent of woodland or wetlands in terrestrial ecosystems, the observed changes in the hydroclimate of southeastern Africa-both in terms of its long-term state and marked precessional variability-could have had a role in the evolution of early hominins, particularly in the extinction of Paranthropus robustus.}, } @article {pmid29988060, year = {2018}, author = {Dolgin, E}, title = {How to start a lab when funds are tight.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {291-293}, doi = {10.1038/d41586-018-05655-3}, pmid = {29988060}, issn = {1476-4687}, mesh = {Africa ; *Budgets ; Canada ; Commerce/economics ; Laboratories/*economics ; Recycling/*economics ; Research/*economics/*instrumentation ; Research Personnel/*economics ; United Kingdom ; }, } @article {pmid29988058, year = {2018}, author = {Knowlton, N}, title = {How rats wreak havoc on coral reefs.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {190-191}, doi = {10.1038/d41586-018-05355-y}, pmid = {29988058}, issn = {1476-4687}, } @article {pmid29988055, year = {2018}, author = {Greene, M}, title = {The imperial roots of climate science.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {178-179}, doi = {10.1038/d41586-018-05650-8}, pmid = {29988055}, issn = {1476-4687}, } @article {pmid29988052, year = {2018}, author = {Tordoff, J and Weiss, R}, title = {Self-organizing multicellular structures designed using synthetic biology.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {184-185}, doi = {10.1038/d41586-018-05564-5}, pmid = {29988052}, issn = {1476-4687}, mesh = {*Artificial Cells ; Cell Communication ; *Synthetic Biology ; }, } @article {pmid29988051, year = {2018}, author = {Waller, LA}, title = {Estimate suggests many infant deaths in sub-Saharan Africa attributable to air pollution.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {188-189}, doi = {10.1038/d41586-018-05394-5}, pmid = {29988051}, issn = {1476-4687}, } @article {pmid29988050, year = {2018}, author = {Quinet, A and Vindigni, A}, title = {Superfast DNA replication causes damage in cancer cells.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {186-187}, doi = {10.1038/d41586-018-05501-6}, pmid = {29988050}, issn = {1476-4687}, } @article {pmid29988048, year = {2018}, author = {Pinger, J and Nešić, D and Ali, L and Aresta-Branco, F and Lilic, M and Chowdhury, S and Kim, HS and Verdi, J and Raper, J and Ferguson, MAJ and Papavasiliou, FN and Stebbins, CE}, title = {African trypanosomes evade immune clearance by O-glycosylation of the VSG surface coat.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {932-938}, pmid = {29988048}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 AI085973/AI/NIAID NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; }, abstract = {The African trypanosome Trypanosoma brucei spp. is a paradigm for antigenic variation, the orchestrated alteration of cell surface molecules to evade host immunity. The parasite elicits robust antibody-mediated immune responses to its variant surface glycoprotein (VSG) coat, but evades immune clearance by repeatedly accessing a large genetic VSG repertoire and 'switching' to antigenically distinct VSGs. This persistent immune evasion has been ascribed exclusively to amino-acid variance on the VSG surface presented by a conserved underlying protein architecture. We establish here that this model does not account for the scope of VSG structural and biochemical diversity. The 1.4-Å-resolution crystal structure of the variant VSG3 manifests divergence in the tertiary fold and oligomeric state. The structure also reveals an O-linked carbohydrate on the top surface of VSG3. Mass spectrometric analysis indicates that this O-glycosylation site is heterogeneously occupied in VSG3 by zero to three hexose residues and is also present in other VSGs. We demonstrate that this O-glycosylation increases parasite virulence by impairing the generation of protective immunity. These data alter the paradigm of antigenic variation by the African trypanosome, expanding VSG variability beyond amino-acid sequence to include surface post-translational modifications with immunomodulatory impact.}, } @article {pmid29987521, year = {2018}, author = {Hua, M and Guo, J and Li, M and Chen, C and Zhang, Y and Song, C and Jiang, D and Du, P and Zeng, H}, title = {A Dual-Replicon Shuttle Vector System for Heterologous Gene Expression in a Broad Range of Gram-Positive and Gram-Negative Bacteria.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29987521}, issn = {1432-0991}, support = {81702038//the National Natural Science Foundation of China/ ; 81571956//the National Natural Science Foundation of China/ ; }, abstract = {Origin of replication (ori in theta-replicating plasmids or dso in rolling circle replicating plasmids) initiates plasmid replication in a broad range of bacteria. These two kinds of plasmids were both identified in Streptococcus, a genus composed of both human commensal bacteria and pathogens with the ability to cause severe community-acquired infections, including meningitides, septicemia, and respiratory tract diseases. Given the important roles of Streptococcus in the exchange of genetic elements with other symbiotic microbes, the genotypes and phenotypes of both Streptococcus spp. and other symbiotic species could be changed during colonization of the host. Therefore, an improved plasmid system is required to study the functional, complicated, and changeable genomes of Streptococcus. In this study, a dual-replicon shuttle vector system named pDRE was constructed to achieve heterologous gene expression. The vector system contained theta replicon for Escherichia coli. The origin of rolling circle replicon was synthesized according to pMV158 in Gram-positive bacteria. By measuring the products of inserted genes at multiple cloning sites, the ability of this vector system in the replication and expression of heterologous genes was assessed in four Streptococcus and three other Gram-positive bacteria: Bacillus subtilis, Lactococcus lactis, and Staphylococcus aureus. The results showed that the newly constructed vector could simultaneously replicate and express heterologous genes in a broad range of Gram-positive and Gram-negative bacteria, thus providing a potentially powerful genetic tool for further functional analysis.}, } @article {pmid29987491, year = {2018}, author = {O'Keefe, H and Queen, RA and Meldau, S and Lord, P and Elson, JL}, title = {Haplogroup Context is Less Important in the Penetrance of Mitochondrial DNA Complex I Mutations Compared to mt-tRNA Mutations.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {29987491}, issn = {1432-1432}, abstract = {Mitochondrial diseases are a highly complex, heterogeneous group of disorders. Mitochondrial DNA variants that are linked to disease can exhibit variable expression and penetrance. This has an implication for mitochondrial diagnostics as variants that cause disease in one individual may not in another. It has been suggested that the sequence context in which a variant arises could influence the genotype-phenotype relationship. However, the consequence of sequence variation between different haplogroups on the expression of disease is not well understood. European haplogroups are the most widely studied. To ensure accurate diagnostics for patients globally, we first need to understand how, if at all, the sequence context in which a variant arises contributes to the manifestion of disease. To help us understand this, we used 2752 sequences from 33 non-human species that do not have disease. We searched for variants in the seven complex I genes that are associated with disease in humans. Our findings indicate that only three reported pathogenic complex I variants have arisen in these species. More importantly, only one of these, m.3308T>C, has arisen with its associated amino acid change in the studied non-human species. With the status of m.3308T>C as a disease causing variant being a matter of debate. This is a stark contrast to previous findings in the mitochondrial tRNA genes and suggests that sequence context may be less important in the complex I genes. This information will help us improve the identification and diagnosis of mitochondrial DNA variants in non-European populations.}, } @article {pmid29987414, year = {2018}, author = {Barnett, AA and Thomas, RH}, title = {Early segmentation in the mite Archegozetes longisetosus reveals conserved and derived aspects of chelicerate development.}, journal = {Development genes and evolution}, volume = {}, number = {}, pages = {}, pmid = {29987414}, issn = {1432-041X}, support = {DEB-0717389//National Science Foundation/ ; }, abstract = {The arthropod body plan is comprised of several repeating segments along the anteroposterior body axis. This high degree of conservation, however, obfuscates the wide degree of underlying developmental variation present across and within arthropod groups. In chelicerates, the arthropod clade containing mites, spiders, scorpions, and horseshoe crabs, development is the most similar at the stages following early germ band segmentation. Comparative studies of chelicerate segmentation prior to these events, however, remain scarce. In order to elucidate and identify possible shared and derived aspects of chelicerate segmentation, we followed the early prosomal (anterior) segmentation in the model mite Archegozetes longisetosus using the expression of the conserved segmental marker hedgehog (hh). Our data indicate that the ancestral chelicerate likely utilized the gene hedgehog in a group of cells surrounding the germ disc. We also provide evidence that chelicerate segmentation, albeit via the conserved "short/intermediate germ" mode, progresses differently in the prosoma between Archegozetes and spiders and thus early, anterior segmentation in chelicerates is heterochronic.}, } @article {pmid29987052, year = {2018}, author = {He, Y and Liu, JC and Luo, L and Wang, YG and Zhu, J and Du, Y and Li, J and Mao, SX and Wang, C}, title = {Size-dependent dynamic structures of supported gold nanoparticles in CO oxidation reaction condition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7700-7705}, pmid = {29987052}, issn = {1091-6490}, abstract = {Gold (Au) catalysts exhibit a significant size effect, but its origin has been puzzling for a long time. It is generally believed that supported Au clusters are more or less rigid in working condition, which inevitably leads to the general speculation that the active sites are immobile. Here, by using atomic resolution in situ environmental transmission electron microscopy, we report size-dependent structure dynamics of single Au nanoparticles on ceria (CeO2) in CO oxidation reaction condition at room temperature. While large Au nanoparticles remain rigid in the catalytic working condition, ultrasmall Au clusters lose their intrinsic structures and become disordered, featuring vigorous structural rearrangements and formation of dynamic low-coordinated atoms on surface. Ab initio molecular-dynamics simulations reveal that the interaction between ultrasmall Au cluster and CO molecules leads to the dynamic structural responses, demonstrating that the shape of the catalytic particle under the working condition may totally differ from the shape under the static condition. The present observation provides insight on the origin of superior catalytic properties of ultrasmall gold clusters.}, } @article {pmid29987051, year = {2018}, author = {Duren, Z and Chen, X and Zamanighomi, M and Zeng, W and Satpathy, AT and Chang, HY and Wang, Y and Wong, WH}, title = {Integrative analysis of single-cell genomics data by coupled nonnegative matrix factorizations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7723-7728}, pmid = {29987051}, issn = {1091-6490}, support = {P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 GM109836/GM/NIGMS NIH HHS/United States ; R01 HG007834/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; *Databases, Genetic ; Humans ; *Models, Genetic ; Sequence Analysis, RNA/*methods ; }, abstract = {When different types of functional genomics data are generated on single cells from different samples of cells from the same heterogeneous population, the clustering of cells in the different samples should be coupled. We formulate this "coupled clustering" problem as an optimization problem and propose the method of coupled nonnegative matrix factorizations (coupled NMF) for its solution. The method is illustrated by the integrative analysis of single-cell RNA-sequencing (RNA-seq) and single-cell ATAC-sequencing (ATAC-seq) data.}, } @article {pmid29987050, year = {2018}, author = {Xiao, T and Li, W and Wang, X and Xu, H and Yang, J and Wu, Q and Huang, Y and Geradts, J and Jiang, P and Fei, T and Chi, D and Zang, C and Liao, Q and Rennhack, J and Andrechek, E and Li, N and Detre, S and Dowsett, M and Jeselsohn, RM and Liu, XS and Brown, M}, title = {Estrogen-regulated feedback loop limits the efficacy of estrogen receptor-targeted breast cancer therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7869-7878}, pmid = {29987050}, issn = {1091-6490}, support = {P01 CA080111/CA/NCI NIH HHS/United States ; R01 HG008728/HG/NHGRI NIH HHS/United States ; U01 CA180980/CA/NCI NIH HHS/United States ; //Department of Health/United Kingdom ; }, mesh = {Breast Neoplasms/*drug therapy/genetics/metabolism/pathology ; Estrogens/*pharmacology ; Female ; Gene Expression Regulation, Enzymologic/drug effects ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MCF-7 Cells ; Neoplasm Proteins/*biosynthesis/genetics ; Receptors, Estrogen/*biosynthesis/genetics ; p21-Activated Kinases/biosynthesis/genetics ; src-Family Kinases/biosynthesis/genetics ; }, abstract = {Endocrine therapy resistance invariably develops in advanced estrogen receptor-positive (ER+) breast cancer, but the underlying mechanisms are largely unknown. We have identified C-terminal SRC kinase (CSK) as a critical node in a previously unappreciated negative feedback loop that limits the efficacy of current ER-targeted therapies. Estrogen directly drives CSK expression in ER+ breast cancer. At low CSK levels, as is the case in patients with ER+ breast cancer resistant to endocrine therapy and with the poorest outcomes, the p21 protein-activated kinase 2 (PAK2) becomes activated and drives estrogen-independent growth. PAK2 overexpression is also associated with endocrine therapy resistance and worse clinical outcome, and the combination of a PAK2 inhibitor with an ER antagonist synergistically suppressed breast tumor growth. Clinical approaches to endocrine therapy-resistant breast cancer must overcome the loss of this estrogen-induced negative feedback loop that normally constrains the growth of ER+ tumors.}, } @article {pmid29987049, year = {2018}, author = {Gazit, S and Assaad, FF and Sachdev, S and Vishwanath, A and Wang, C}, title = {Confinement transition of ℤ2 gauge theories coupled to massless fermions: Emergent quantum chromodynamics and SO(5) symmetry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E6987-E6995}, pmid = {29987049}, issn = {1091-6490}, abstract = {We study a model of fermions on the square lattice at half-filling coupled to an Ising gauge theory that was recently shown in Monte Carlo simulations to exhibit [Formula: see text] topological order and massless Dirac fermion excitations. On tuning parameters, a confining phase with broken symmetry (an antiferromagnet in one choice of Hamiltonian) was also established, and the transition between these phases was found to be continuous, with coincident onset of symmetry breaking and confinement. While the confinement transition in pure gauge theories is well-understood in terms of condensing magnetic flux excitations, the same transition in the presence of gapless fermions is a challenging problem owing to the statistical interactions between fermions and the condensing flux excitations. The conventional scenario then proceeds via a two-step transition, involving a symmetry-breaking transition leading to gapped fermions followed by confinement. In contrast, here, using quantum Monte Carlo simulations, we provide further evidence for a direct, continuous transition and also find numerical evidence for an enlarged [Formula: see text] symmetry rotating between antiferromagnetism and valence bond solid orders proximate to criticality. Guided by our numerical finding, we develop a field theory description of the direct transition involving an emergent nonabelian [[Formula: see text]] gauge theory and a matrix Higgs field. We contrast our results with the conventional Gross-Neveu-Yukawa transition.}, } @article {pmid29987048, year = {2018}, author = {Akbarpour, M and Jackson, MO}, title = {Diffusion in networks and the virtue of burstiness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E6996-E7004}, pmid = {29987048}, issn = {1091-6490}, mesh = {*Communicable Diseases/epidemiology/transmission ; *Disease Transmission, Infectious ; Humans ; *Infection/epidemiology/transmission ; *Models, Biological ; }, abstract = {Whether an idea, information, or infection diffuses throughout a society depends not only on the structure of the network of interactions, but also on the timing of those interactions. People are not always available to interact with others, and people differ in the timing of when they are active. Some people are active for long periods and then inactive for long periods, while others switch more frequently from being active to inactive and back. We show that maximizing diffusion in classic contagion processes requires heterogeneous activity patterns across agents. In particular, maximizing diffusion comes from mixing two extreme types of people: those who are stationary for long periods of time, changing from active to inactive or back only infrequently, and others who alternate frequently between being active and inactive.}, } @article {pmid29987047, year = {2018}, author = {Verruto, J and Francis, K and Wang, Y and Low, MC and Greiner, J and Tacke, S and Kuzminov, F and Lambert, W and McCarren, J and Ajjawi, I and Bauman, N and Kalb, R and Hannum, G and Moellering, ER}, title = {Unrestrained markerless trait stacking in Nannochloropsis gaditana through combined genome editing and marker recycling technologies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7015-E7022}, pmid = {29987047}, issn = {1091-6490}, mesh = {*Acyl-CoA Oxidase/genetics/metabolism ; *CRISPR-Cas Systems ; *Gene Editing ; Light-Harvesting Protein Complexes/genetics/metabolism ; *Lipids/biosynthesis/genetics ; *Quantitative Trait, Heritable ; *Stramenopiles/genetics/metabolism ; }, abstract = {Robust molecular tool kits in model and industrial microalgae are key to efficient targeted manipulation of endogenous and foreign genes in the nuclear genome for basic research and, as importantly, for the development of algal strains to produce renewable products such as biofuels. While Cas9-mediated gene knockout has been demonstrated in a small number of algal species with varying efficiency, the ability to stack traits or generate knockout mutations in two or more loci are often severely limited by selectable agent availability. This poses a critical hurdle in developing production strains, which require stacking of multiple traits, or in probing functionally redundant gene families. Here, we combine Cas9 genome editing with an inducible Cre recombinase in the industrial alga Nannochloropsis gaditana to generate a strain, NgCas9+Cre+, in which the potentially unlimited stacking of knockouts and addition of new genes is readily achievable. Cre-mediated marker recycling is first demonstrated in the removal of the selectable marker and GFP reporter transgenes associated with the Cas9/Cre construct in NgCas9+Cre+ Next, we show the proof-of-concept generation of a markerless knockout in a gene encoding an acyl-CoA oxidase (Aco1), as well as the markerless recapitulation of a 2-kb insert in the ZnCys gene 5'-UTR, which results in a doubling of wild-type lipid productivity. Finally, through an industrially oriented process, we generate mutants that exhibit up to ∼50% reduction in photosynthetic antennae size by markerless knockout of seven genes in the large light-harvesting complex gene family.}, } @article {pmid29987046, year = {2018}, author = {Wang, P and Dreger, M and Madrazo, E and Williams, CJ and Samaniego, R and Hodson, NW and Monroy, F and Baena, E and Sánchez-Mateos, P and Hurlstone, A and Redondo-Muñoz, J}, title = {WDR5 modulates cell motility and morphology and controls nuclear changes induced by a 3D environment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {34}, pages = {8581-8586}, pmid = {29987046}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {*Cell Movement ; *Cell Polarity ; Chromatin/genetics/*metabolism/ultrastructure ; *Epigenesis, Genetic ; Histone-Lysine N-Methyltransferase/chemistry/genetics/*metabolism ; Humans ; Jurkat Cells ; Microscopy, Atomic Force ; Myosin-Light-Chain Kinase/genetics/metabolism ; Nuclear Proteins/chemistry/genetics/*metabolism ; }, abstract = {Cell migration through extracellular matrices requires nuclear deformation, which depends on nuclear stiffness. In turn, chromatin structure contributes to nuclear stiffness, but the mechanosensing pathways regulating chromatin during cell migration remain unclear. Here, we demonstrate that WD repeat domain 5 (WDR5), an essential component of H3K4 methyltransferase complexes, regulates cell polarity, nuclear deformability, and migration of lymphocytes in vitro and in vivo, independent of transcriptional activity, suggesting nongenomic functions for WDR5. Similarly, depletion of RbBP5 (another H3K4 methyltransferase subunit) promotes similar defects. We reveal that a 3D environment increases the H3K4 methylation dependent on WDR5 and results in a globally less compacted chromatin conformation. Further, using atomic force microscopy, nuclear particle tracking, and nuclear swelling experiments, we detect changes in nuclear mechanics that accompany the epigenetic changes induced in 3D conditions. Indeed, nuclei from cells in 3D environments were softer, and thereby more deformable, compared with cells in suspension or cultured in 2D conditions, again dependent on WDR5. Dissecting the underlying mechanism, we determined that actomyosin contractility, through the phosphorylation of myosin by MLCK (myosin light chain kinase), controls the interaction of WDR5 with other components of the methyltransferase complex, which in turn up-regulates H3K4 methylation activation in 3D conditions. Taken together, our findings reveal a nongenomic function for WDR5 in regulating H3K4 methylation induced by 3D environments, physical properties of the nucleus, cell polarity, and cell migratory capacity.}, } @article {pmid29987045, year = {2018}, author = {Wu, H and Chen, W and Zhao, F and Zhou, Q and Reinach, PS and Deng, L and Ma, L and Luo, S and Srinivasalu, N and Pan, M and Hu, Y and Pei, X and Sun, J and Ren, R and Xiong, Y and Zhou, Z and Zhang, S and Tian, G and Fang, J and Zhang, L and Lang, J and Wu, D and Zeng, C and Qu, J and Zhou, X}, title = {Scleral hypoxia is a target for myopia control.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7091-E7100}, pmid = {29987045}, issn = {1091-6490}, mesh = {Animals ; Disease Models, Animal ; Eukaryotic Initiation Factor-2/metabolism ; Extracellular Matrix/*metabolism/pathology ; Eye Proteins/metabolism ; Guinea Pigs ; Humans ; *Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Male ; Mice ; Myopia/metabolism/pathology/*therapy ; Sclera/blood supply/*metabolism/pathology ; *Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Worldwide, myopia is the leading cause of visual impairment. It results from inappropriate extension of the ocular axis and concomitant declines in scleral strength and thickness caused by extracellular matrix (ECM) remodeling. However, the identities of the initiators and signaling pathways that induce scleral ECM remodeling in myopia are unknown. Here, we used single-cell RNA-sequencing to identify pathways activated in the sclera during myopia development. We found that the hypoxia-signaling, the eIF2-signaling, and mTOR-signaling pathways were activated in murine myopic sclera. Consistent with the role of hypoxic pathways in mouse model of myopia, nearly one third of human myopia risk genes from the genome-wide association study and linkage analyses interact with genes in the hypoxia-inducible factor-1α (HIF-1α)-signaling pathway. Furthermore, experimental myopia selectively induced HIF-1α up-regulation in the myopic sclera of both mice and guinea pigs. Additionally, hypoxia exposure (5% O2) promoted myofibroblast transdifferentiation with down-regulation of type I collagen in human scleral fibroblasts. Importantly, the antihypoxia drugs salidroside and formononetin down-regulated HIF-1α expression as well as the phosphorylation levels of eIF2α and mTOR, slowing experimental myopia progression without affecting normal ocular growth in guinea pigs. Furthermore, eIF2α phosphorylation inhibition suppressed experimental myopia, whereas mTOR phosphorylation induced myopia in normal mice. Collectively, these findings defined an essential role of hypoxia in scleral ECM remodeling and myopia development, suggesting a therapeutic approach to control myopia by ameliorating hypoxia.}, } @article {pmid29987044, year = {2018}, author = {Gualdoni, GA and Mayer, KA and Kapsch, AM and Kreuzberg, K and Puck, A and Kienzl, P and Oberndorfer, F and Frühwirth, K and Winkler, S and Blaas, D and Zlabinger, GJ and Stöckl, J}, title = {Rhinovirus induces an anabolic reprogramming in host cell metabolism essential for viral replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7158-E7165}, pmid = {29987044}, issn = {1091-6490}, mesh = {Animals ; Deoxyglucose/pharmacology ; Female ; Glucose Transporter Type 1/genetics/metabolism ; Lipogenesis/drug effects/genetics ; Mice ; Nucleotides/biosynthesis/genetics ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Picornaviridae Infections/drug therapy/genetics/*metabolism/pathology ; Rhinovirus/*physiology ; Virus Replication/drug effects/*physiology ; }, abstract = {Rhinoviruses (RVs) are responsible for the majority of upper airway infections; despite their high prevalence and the resulting economic burden, effective treatment is lacking. We report here that RV induces metabolic alterations in host cells, which offer an efficient target for antiviral intervention. We show that RV-infected cells rapidly up-regulate glucose uptake in a PI3K-dependent manner. In parallel, infected cells enhance the expression of the PI3K-regulated glucose transporter GLUT1. In-depth metabolomic analysis of RV-infected cells revealed a critical role of glucose mobilization from extracellular and intracellular pools via glycogenolysis for viral replication. Infection resulted in a highly anabolic state, including enhanced nucleotide synthesis and lipogenesis. Consistently, we observed that glucose deprivation from medium and via glycolysis inhibition by 2-deoxyglucose (2-DG) potently impairs viral replication. Metabolomic analysis showed that 2-DG specifically reverts the RV-induced anabolic reprogramming. In addition, treatment with 2-DG inhibited RV infection and inflammation in a murine model. Thus, we demonstrate that the specific metabolic fingerprint of RV infection can be used to identify new targets for therapeutic intervention.}, } @article {pmid29987043, year = {2018}, author = {Nandi, SK and Mandal, R and Bhuyan, PJ and Dasgupta, C and Rao, M and Gov, NS}, title = {A random first-order transition theory for an active glass.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7688-7693}, pmid = {29987043}, issn = {1091-6490}, abstract = {How does nonequilibrium activity modify the approach to a glass? This is an important question, since many experiments reveal the near-glassy nature of the cell interior, remodeled by activity. However, different simulations of dense assemblies of active particles, parametrized by a self-propulsion force, [Formula: see text], and persistence time, [Formula: see text], appear to make contradictory predictions about the influence of activity on characteristic features of glass, such as fragility. This calls for a broad conceptual framework to understand active glasses; here, we extend the random first-order transition (RFOT) theory to a dense assembly of self-propelled particles. We compute the active contribution to the configurational entropy through an effective model of a single particle in a caging potential. This simple active extension of RFOT provides excellent quantitative fits to existing simulation results. We find that whereas [Formula: see text] always inhibits glassiness, the effect of [Formula: see text] is more subtle and depends on the microscopic details of activity. In doing so, the theory automatically resolves the apparent contradiction between the simulation models. The theory also makes several testable predictions, which we verify by both existing and new simulation data, and should be viewed as a step toward a more rigorous analytical treatment of active glass.}, } @article {pmid29987042, year = {2018}, author = {Mann, TH and Shapiro, L}, title = {Integration of cell cycle signals by multi-PAS domain kinases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7166-E7173}, pmid = {29987042}, issn = {1091-6490}, support = {R01 GM032506/GM/NIGMS NIH HHS/United States ; R35 GM118071/GM/NIGMS NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry ; Caulobacter crescentus/chemistry/*enzymology ; Protein Domains ; Protein Kinases/*chemistry ; *Protein Multimerization ; Protein Structure, Quaternary ; }, abstract = {Spatial control of intracellular signaling relies on signaling proteins sensing their subcellular environment. In many cases, a large number of upstream signals are funneled to a master regulator of cellular behavior, but it remains unclear how individual proteins can rapidly integrate a complex array of signals within the appropriate spatial niche within the cell. As a model for how subcellular spatial information can control signaling activity, we have reconstituted the cell pole-specific control of the master regulator kinase/phosphatase CckA from the asymmetrically dividing bacterium Caulobacter crescentus CckA is active as a kinase only when it accumulates within a microdomain at the new cell pole, where it colocalizes with the pseudokinase DivL. Both proteins contain multiple PAS domains, a multifunctional class of sensory domains present across the kingdoms of life. Here, we show that CckA uses its PAS domains to integrate information from DivL and its own oligomerization state to control the balance of its kinase and phosphatase activities. We reconstituted the DivL-CckA complex on liposomes in vitro and found that DivL directly controls the CckA kinase/phosphatase switch, and that stimulation of either CckA catalytic activity depends on the second of its two PAS domains. We further show that CckA oligomerizes through a multidomain interaction that is critical for stimulation of kinase activity by DivL, while DivL stimulation of CckA phosphatase activity is independent of CckA homooligomerization. Our results broadly demonstrate how signaling factors can leverage information from their subcellular niche to drive spatiotemporal control of cell signaling.}, } @article {pmid29987041, year = {2018}, author = {}, title = {Retraction for Ajees et al., Crystal structure of human apolipoprotein A-I: Insights into its protective effect against cardiovascular diseases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6966}, doi = {10.1073/pnas.1806430115}, pmid = {29987041}, issn = {1091-6490}, } @article {pmid29987040, year = {2018}, author = {Samoray, C}, title = {QnAs with Dean H. Roemmich.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7646-7647}, doi = {10.1073/pnas.1810731115}, pmid = {29987040}, issn = {1091-6490}, } @article {pmid29987039, year = {2018}, author = {Merkouris, S and Barde, YA and Binley, KE and Allen, ND and Stepanov, AV and Wu, NC and Grande, G and Lin, CW and Li, M and Nan, X and Chacon-Fernandez, P and DiStefano, PS and Lindsay, RM and Lerner, RA and Xie, J}, title = {Fully human agonist antibodies to TrkB using autocrine cell-based selection from a combinatorial antibody library.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7023-E7032}, pmid = {29987039}, issn = {1091-6490}, mesh = {*Autocrine Communication ; Cell Line ; GABAergic Neurons/*metabolism ; *Gene Library ; Humans ; Membrane Glycoproteins/*agonists/genetics/metabolism ; Phosphorylation/drug effects ; Receptor, trkB/*agonists/genetics/metabolism ; Signal Transduction/*drug effects ; *Single-Chain Antibodies/genetics/pharmacology ; Transcription, Genetic/*drug effects ; }, abstract = {The diverse physiological roles of the neurotrophin family have long prompted exploration of their potential as therapeutic agents for nerve injury and neurodegenerative diseases. To date, clinical trials of one family member, brain-derived neurotrophic factor (BDNF), have disappointingly failed to meet desired endpoints. Contributing to these failures is the fact that BDNF is pharmaceutically a nonideal biologic drug candidate. It is a highly charged, yet is a net hydrophobic molecule with a low molecular weight that confers a short t1/2 in man. To circumvent these shortcomings of BDNF as a drug candidate, we have employed a function-based cellular screening assay to select activating antibodies of the BDNF receptor TrkB from a combinatorial human short-chain variable fragment antibody library. We report here the successful selection of several potent TrkB agonist antibodies and detailed biochemical and physiological characterization of one such antibody, ZEB85. By using a human TrkB reporter cell line and BDNF-responsive GABAergic neurons derived from human ES cells, we demonstrate that ZEB85 is a full agonist of TrkB, comparable in potency to BDNF toward human neurons in activation of TrkB phosphorylation, canonical signal transduction, and mRNA transcriptional regulation.}, } @article {pmid29987038, year = {2018}, author = {Rosner, H and Leithe-Jasper, A and Carrillo-Cabrera, W and Schnelle, W and Ackerbauer, SV and Gamza, MB and Grin, Y}, title = {Local magnetism in MnSiPt rules the chemical bond.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7706-7710}, pmid = {29987038}, issn = {1091-6490}, abstract = {Among intermetallic compounds, ternary phases with the simple stoichiometric ratio 1:1:1 form one of the largest families. More than 15 structural patterns have been observed for several hundred compounds constituting this group. This, on first glance unexpected, finding is a consequence of the complex mechanism of chemical bonding in intermetallic structures, allowing for large diversity. Their formation process can be understood based on a hierarchy of energy scales: The main share is contributed by covalent and ionic interactions in accordance with the electronic needs of the participating elements. However, smaller additional atomic interactions may still tip the scales. Here, we demonstrate that the local spin polarization of paramagnetic manganese in the new compound MnSiPt rules the adopted TiNiSi-type crystal structure. Combining a thorough experimental characterization with a theoretical analysis of the energy landscape and the chemical bonding of MnSiPt, we show that the paramagnetism of the Mn atoms suppresses the formation of Mn-Mn bonds, deciding between competing crystal structures.}, } @article {pmid29987037, year = {2018}, author = {Li, W and Young, JF and Sun, J}, title = {NADPH oxidase-generated reactive oxygen species in mature follicles are essential for Drosophila ovulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7765-7770}, pmid = {29987037}, issn = {1091-6490}, support = {R01 HD086175/HD/NICHD NIH HHS/United States ; S10 OD016435/OD/NIH HHS/United States ; }, mesh = {Animals ; Drosophila Proteins/*metabolism ; Drosophila melanogaster ; Female ; Hydrogen Peroxide/*metabolism ; Matrix Metalloproteinase 2/metabolism ; NADPH Oxidases/*metabolism ; Ovarian Follicle/*metabolism ; Ovulation/*physiology ; Signal Transduction/*physiology ; Superoxide Dismutase/*metabolism ; }, abstract = {Ovarian reactive oxygen species (ROS) are believed to regulate ovulation in mammals, but the details of ROS production in follicles and the role of ROS in ovulation in other species remain underexplored. In Drosophila ovulation, matrix metalloproteinase 2 (MMP2) is required for follicle rupture by degradation of posterior follicle cells surrounding a mature oocyte. We recently demonstrated that MMP2 activation and follicle rupture are regulated by the neuronal hormone octopamine (OA) and the octopamine receptor in mushroom body (OAMB). In the current study, we investigated the role of the superoxide-generating enzyme NADPH oxidase (NOX) in Drosophila ovulation. We report that Nox is highly enriched in mature follicle cells and that Nox knockdown in these cells leads to a reduction in superoxide and to defective ovulation. Similar to MMP2 activation, NOX enzymatic activity is also controlled by the OA/OAMB-Ca2+ signaling pathway. In addition, we report that extracellular superoxide dismutase 3 (SOD3) is required to convert superoxide to hydrogen peroxide, which acts as the key signaling molecule for follicle rupture, independent of MMP2 activation. Given that Nox homologs are expressed in mammalian follicles, the NOX-dependent hydrogen peroxide signaling pathway that we describe could play a conserved role in regulating ovulation in other species.}, } @article {pmid29987036, year = {2018}, author = {Li, WL and Chen, TT and Xing, DH and Chen, X and Li, J and Wang, LS}, title = {Observation of highly stable and symmetric lanthanide octa-boron inverse sandwich complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E6972-E6977}, pmid = {29987036}, issn = {1091-6490}, abstract = {While boron forms a wide range of metal borides with important industrial applications, there has been relatively little attention devoted to lanthanide boride clusters. Here we report a joint photoelectron spectroscopy and quantum chemical study on two octa-boron di-lanthanide clusters, Ln2B8- (Ln = La, Pr). We found that these clusters form highly stable inverse sandwich structures, [Ln-B8-Ln]-, with strong Ln and B8 bonding via interactions between the Ln 5d orbitals and the delocalized σ and π orbitals on the B8 ring. A (d-p)δ bond, involving the 5dδ and the antibonding π orbital of the B8 ring, is observed to be important in the Ln-B8 interactions. The highly symmetric inverse sandwich structures are overwhelmingly more stable than any other isomers. Upon electron detachment, the (d-p)δ orbitals become half-filled, giving rise to a triplet ground state for neutral La2B8 In addition to the two unpaired electrons in the (d-p)δ orbitals upon electron detachment, the neutral Pr2B8 complex also contains two unpaired 4f electrons on each Pr center. The six unpaired spins in Pr2B8 are ferromagnetically coupled to give rise to a septuplet ground state. The current work suggests that highly magnetic Ln…B8…Ln inverse sandwiches or 1D Ln…B8…Ln nanowires may be designed with novel electronic and magnetic properties.}, } @article {pmid29987035, year = {2018}, author = {Kiktev, DA and Sheng, Z and Lobachev, KS and Petes, TD}, title = {GC content elevates mutation and recombination rates in the yeast Saccharomyces cerevisiae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7109-E7118}, pmid = {29987035}, issn = {1091-6490}, support = {R01 GM024110/GM/NIGMS NIH HHS/United States ; R01 GM052319/GM/NIGMS NIH HHS/United States ; R35 GM118020/GM/NIGMS NIH HHS/United States ; }, mesh = {*Base Composition ; *Base Sequence ; *Recombination, Genetic ; Saccharomyces cerevisiae/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/*genetics/metabolism ; *Sequence Deletion ; }, abstract = {The chromosomes of many eukaryotes have regions of high GC content interspersed with regions of low GC content. In the yeast Saccharomyces cerevisiae, high-GC regions are often associated with high levels of meiotic recombination. In this study, we constructed URA3 genes that differ substantially in their base composition [URA3-AT (31% GC), URA3-WT (43% GC), and URA3-GC (63% GC)] but encode proteins with the same amino acid sequence. The strain with URA3-GC had an approximately sevenfold elevated rate of ura3 mutations compared with the strains with URA3-WT or URA3-AT About half of these mutations were single-base substitutions and were dependent on the error-prone DNA polymerase ζ. About 30% were deletions or duplications between short (5-10 base) direct repeats resulting from DNA polymerase slippage. The URA3-GC gene also had elevated rates of meiotic and mitotic recombination relative to the URA3-AT or URA3-WT genes. Thus, base composition has a substantial effect on the basic parameters of genome stability and evolution.}, } @article {pmid29987034, year = {2018}, author = {Filareto, A and Maguire-Nguyen, K and Gan, Q and Aldanondo, G and Machado, L and Chamberlain, JS and Rando, TA}, title = {Monitoring disease activity noninvasively in the mdx model of Duchenne muscular dystrophy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7741-7746}, pmid = {29987034}, issn = {1091-6490}, support = {R01 AR040864/AR/NIAMS NIH HHS/United States ; R37 AG023806/AG/NIA NIH HHS/United States ; I01 RX001222/RX/RRD VA/United States ; R01 AG055755/AG/NIA NIH HHS/United States ; I01 BX002324/BX/BLRD VA/United States ; }, mesh = {Animals ; *Dependovirus ; *Dystrophin/biosynthesis/genetics ; *Genetic Therapy ; Humans ; Mice ; Mice, Transgenic ; *Muscle Fibers, Skeletal/metabolism/pathology ; *Muscular Dystrophy, Duchenne/genetics/metabolism/physiopathology/therapy ; *Transduction, Genetic ; }, abstract = {Duchenne muscular dystrophy (DMD) is a rare, muscle degenerative disease resulting from the absence of the dystrophin protein. DMD is characterized by progressive loss of muscle fibers, muscle weakness, and eventually loss of ambulation and premature death. Currently, there is no cure for DMD and improved methods of disease monitoring are crucial for the development of novel treatments. In this study, we describe a new method of assessing disease progression noninvasively in the mdx model of DMD. The reporter mice, which we term the dystrophic Degeneration Reporter strains, contain an inducible CRE-responsive luciferase reporter active in mature myofibers. In these mice, muscle degeneration is reflected in changes in the level of luciferase expression, which can be monitored using noninvasive, bioluminescence imaging. We monitored the natural history and disease progression in these dystrophic report mice and found that decreases in luciferase signals directly correlated with muscle degeneration. We further demonstrated that this reporter strain, as well as a previously reported Regeneration Reporter strain, successfully reveals the effectiveness of a gene therapy treatment following systemic administration of a recombinant adeno-associated virus-6 (rAAV-6) encoding a microdystrophin construct. Our data demonstrate the value of these noninvasive imaging modalities for monitoring disease progression and response to therapy in mouse models of muscular dystrophy.}, } @article {pmid29987033, year = {2018}, author = {Gueneli, N and McKenna, AM and Ohkouchi, N and Boreham, CJ and Beghin, J and Javaux, EJ and Brocks, JJ}, title = {1.1-billion-year-old porphyrins establish a marine ecosystem dominated by bacterial primary producers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E6978-E6986}, pmid = {29987033}, issn = {1091-6490}, mesh = {Aquatic Organisms/*physiology ; Chlorobi/*genetics/metabolism ; Chromatiaceae/*genetics ; *Ecosystem ; *Evolution, Molecular ; Porphyrins/*genetics/metabolism ; *Water Microbiology ; }, abstract = {The average cell size of marine phytoplankton is critical for the flow of energy and nutrients from the base of the food web to higher trophic levels. Thus, the evolutionary succession of primary producers through Earth's history is important for our understanding of the radiation of modern protists ∼800 million years ago and the emergence of eumetazoan animals ∼200 million years later. Currently, it is difficult to establish connections between primary production and the proliferation of large and complex organisms because the mid-Proterozoic (∼1,800-800 million years ago) rock record is nearly devoid of recognizable phytoplankton fossils. We report the discovery of intact porphyrins, the molecular fossils of chlorophylls, from 1,100-million-year-old marine black shales of the Taoudeni Basin (Mauritania), 600 million years older than previous findings. The porphyrin nitrogen isotopes (δ15Npor = 5.6-10.2‰) are heavier than in younger sedimentary sequences, and the isotopic offset between sedimentary bulk nitrogen and porphyrins (εpor = -5.1 to -0.5‰) points to cyanobacteria as dominant primary producers. Based on fossil carotenoids, anoxygenic green (Chlorobiacea) and purple sulfur bacteria (Chromatiaceae) also contributed to photosynthate. The low εpor values, in combination with a lack of diagnostic eukaryotic steranes in the time interval of 1,600-1,000 million years ago, demonstrate that algae played an insignificant role in mid-Proterozoic oceans. The paucity of algae and the small cell size of bacterial phytoplankton may have curtailed the flow of energy to higher trophic levels, potentially contributing to a diminished evolutionary pace toward complex eukaryotic ecosystems and large and active organisms.}, } @article {pmid29987032, year = {2018}, author = {Cao, X and Zhu, L and Song, X and Hu, Z and Cronan, JE}, title = {Protein moonlighting elucidates the essential human pathway catalyzing lipoic acid assembly on its cognate enzymes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7063-E7072}, pmid = {29987032}, issn = {1091-6490}, support = {R01 AI015650/AI/NIAID NIH HHS/United States ; R37 AI015650/AI/NIAID NIH HHS/United States ; }, mesh = {Acyltransferases/genetics/*metabolism ; Biocatalysis ; Humans ; Ketone Oxidoreductases/metabolism ; Thioctic Acid/genetics/*metabolism ; }, abstract = {The lack of attachment of lipoic acid to its cognate enzyme proteins results in devastating human metabolic disorders. These mitochondrial disorders are evident soon after birth and generally result in early death. The mutations causing specific defects in lipoyl assembly map in three genes, LIAS, LIPT1, and LIPT2 Although physiological roles have been proposed for the encoded proteins, only the LIPT1 protein had been studied at the enzyme level. LIPT1 was reported to catalyze only the second partial reaction of the classical lipoate ligase mechanism. We report that the physiologically relevant LIPT1 enzyme activity is transfer of lipoyl moieties from the H protein of the glycine cleavage system to the E2 subunits of the 2-oxoacid dehydrogenases required for respiration (e.g., pyruvate dehydrogenase) and amino acid degradation. We also report that LIPT2 encodes an octanoyl transferase that initiates lipoyl group assembly. The human pathway is now biochemically defined.}, } @article {pmid29987031, year = {2018}, author = {Li, W and Zhang, X and Yang, Y and Yin, Q and Wang, Y and Li, Y and Wang, C and Wong, SM and Wang, Y and Goldfine, H and Akerley, BJ and Shen, H}, title = {Recognition of conserved antigens by Th17 cells provides broad protection against pulmonary Haemophilus influenzae infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7149-E7157}, pmid = {29987031}, issn = {1091-6490}, support = {R01 AI095740/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigens, Bacterial/*immunology ; Cross Reactions ; Haemophilus Infections/*immunology/pathology/prevention & control ; Haemophilus Vaccines/*immunology ; Haemophilus influenzae/*immunology ; Mice ; Mice, Knockout ; Pneumonia, Bacterial/*immunology/pathology/prevention & control ; Pulmonary Disease, Chronic Obstructive/immunology/microbiology/prevention & control ; Th17 Cells/*immunology/pathology ; }, abstract = {Nontypeable Haemophilus influenzae (NTHi) is a major cause of community acquired pneumonia and exacerbation of chronic obstructive pulmonary disease. A current effort in NTHi vaccine development has focused on generating humoral responses and has been greatly impeded by antigenic variation among the numerous circulating NTHi strains. In this study, we showed that pulmonary immunization of mice with killed NTHi generated broad protection against lung infection by different strains. While passive transfer of immune antibodies protected only against the homologous strain, transfer of immune T cells conferred protection against both homologous and heterologous strains. Further characterization revealed a strong Th17 response that was cross-reactive with different NTHi strains. Responding Th17 cells recognized both cytosolic and membrane-associated antigens, while immune antibodies preferentially responded to surface antigens and were highly strain specific. We further identified several conserved proteins recognized by lung Th17 cells during NTHi infection. Two proteins yielding the strongest responses were tested as vaccine candidates by immunization of mice with purified proteins plus an adjuvant. Immunization induced antigen-specific Th17 cells that recognized different strains and, upon adoptive transfer, conferred protection. Furthermore, immunized mice were protected against challenge with not only NTHi strains but also a fully virulent, encapsulated strain. Together, these results show that the immune mechanism of cross-protection against pneumonia involves Th17 cells, which respond to a broad spectrum of antigens, including those that are highly conserved among NTHi strains. These mechanistic insights suggest that inclusion of Th17 antigens in subunit vaccines offers the advantage of inducing broad protection and complements the current antibody-based approaches.}, } @article {pmid29987030, year = {2018}, author = {Grossman, SR and Engreitz, J and Ray, JP and Nguyen, TH and Hacohen, N and Lander, ES}, title = {Positional specificity of different transcription factor classes within enhancers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7222-E7230}, pmid = {29987030}, issn = {1091-6490}, support = {T32 GM007753/GM/NIGMS NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; }, mesh = {Gene Expression Regulation/*physiology ; Humans ; Jurkat Cells ; Response Elements/*physiology ; Transcription Factors/genetics/*metabolism ; U937 Cells ; }, abstract = {Gene expression is controlled by sequence-specific transcription factors (TFs), which bind to regulatory sequences in DNA. TF binding occurs in nucleosome-depleted regions of DNA (NDRs), which generally encompass regions with lengths similar to those protected by nucleosomes. However, less is known about where within these regions specific TFs tend to be found. Here, we characterize the positional bias of inferred binding sites for 103 TFs within ∼500,000 NDRs across 47 cell types. We find that distinct classes of TFs display different binding preferences: Some tend to have binding sites toward the edges, some toward the center, and some at other positions within the NDR. These patterns are highly consistent across cell types, suggesting that they may reflect TF-specific intrinsic structural or functional characteristics. In particular, TF classes with binding sites at NDR edges are enriched for those known to interact with histones and chromatin remodelers, whereas TFs with central enrichment interact with other TFs and cofactors such as p300. Our results suggest distinct regiospecific binding patterns and functions of TF classes within enhancers.}, } @article {pmid29987029, year = {2018}, author = {}, title = {Correction for Stokes and Purdon, A study of problems encountered in Granger causality analysis from a neuroscience perspective.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6964}, doi = {10.1073/pnas.1809324115}, pmid = {29987029}, issn = {1091-6490}, } @article {pmid29987028, year = {2018}, author = {Li, M and Bao, F and Zhang, Y and Song, W and Chen, C and Zhao, J}, title = {Role of elemental carbon in the photochemical aging of soot.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7717-7722}, pmid = {29987028}, issn = {1091-6490}, abstract = {Soot, which consists of organic carbon (OC) and elemental carbon (EC), is a significant component of the total aerosol mass in the atmosphere. Photochemical oxidation is an important aging pathway for soot. It is commonly believed that OC is photoactive but EC, albeit its strong light absorption, is photochemically inert. Here, by taking advantage of the different light absorption properties of OC and EC, we provide direct experimental evidence that EC also plays an important role in the photochemical aging of soot by initiating the oxidation of OC, even under red light irradiation. We show that nascent soot, in addition to undergoing photochemical oxidation under blue light with a wavelength of 440 nm, undergoes similar oxidation under red light irradiation of λ = 648 nm (L648). However, separated OC (extracted from soot by n-hexane) and EC exhibit little reactivity under L648 These observations indicate that EC plays a pivotal role in photoaging of soot by adsorbing light to initiate the oxidation of OC. Comparison of in situ IR spectra and photoelectrochemical behaviors suggests that EC-initiated photooxidation of OC proceeds through an electron transfer pathway, which is distinct from the photoaging induced by light absorption of OC. Since the absorption spectra of EC have a much larger overlap with the solar spectra than those of OC, our results provide insight into the chemical mechanism leading to rapid soot aging by organic species observed from atmospheric field measurements.}, } @article {pmid29987027, year = {2018}, author = {Wefers, J and van Moorsel, D and Hansen, J and Connell, NJ and Havekes, B and Hoeks, J and van Marken Lichtenbelt, WD and Duez, H and Phielix, E and Kalsbeek, A and Boekschoten, MV and Hooiveld, GJ and Hesselink, MKC and Kersten, S and Staels, B and Scheer, FAJL and Schrauwen, P}, title = {Circadian misalignment induces fatty acid metabolism gene profiles and compromises insulin sensitivity in human skeletal muscle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7789-7794}, pmid = {29987027}, issn = {1091-6490}, support = {R01 DK099512/DK/NIDDK NIH HHS/United States ; R01 HL118601/HL/NHLBI NIH HHS/United States ; R01 DK102696/DK/NIDDK NIH HHS/United States ; R01 HL140574/HL/NHLBI NIH HHS/United States ; R01 DK105072/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Diabetes Mellitus, Type 2/*blood/pathology ; Fatty Acids/*blood ; *Gene Expression Profiling ; *Heart ; Humans ; *Insulin Resistance ; Male ; Muscle, Skeletal/*metabolism/pathology ; Obesity/*blood/pathology ; }, abstract = {Circadian misalignment, such as in shift work, has been associated with obesity and type 2 diabetes. However, direct effects of circadian misalignment on skeletal muscle insulin sensitivity and the muscle molecular circadian clock have never been studied in humans. Here, we investigated insulin sensitivity and muscle metabolism in 14 healthy young lean men [age 22.4 ± 2.8 years; body mass index (BMI) 22.3 ± 2.1 kg/m2 (mean ± SD)] after a 3-d control protocol and a 3.5-d misalignment protocol induced by a 12-h rapid shift of the behavioral cycle. We show that short-term circadian misalignment results in a significant decrease in muscle insulin sensitivity due to a reduced skeletal muscle nonoxidative glucose disposal (rate of disappearance: 23.7 ± 2.4 vs. 18.4 ± 1.4 mg/kg per minute; control vs. misalignment; P = 0.024). Fasting glucose and free fatty acid levels as well as sleeping metabolic rate were higher during circadian misalignment. Molecular analysis of skeletal muscle biopsies revealed that the molecular circadian clock was not aligned to the inverted behavioral cycle, and transcriptome analysis revealed the human PPAR pathway as a key player in the disturbed energy metabolism upon circadian misalignment. Our findings may provide a mechanism underlying the increased risk of type 2 diabetes among shift workers.}, } @article {pmid29987026, year = {2018}, author = {Ke, R and Li, H and Wang, S and Ding, W and Ribeiro, RM and Giorgi, EE and Bhattacharya, T and Barnard, RJO and Hahn, BH and Shaw, GM and Perelson, AS}, title = {Superinfection and cure of infected cells as mechanisms for hepatitis C virus adaptation and persistence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7139-E7148}, pmid = {29987026}, issn = {1091-6490}, support = {R01 OD011095/OD/NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; R01 AI028433/AI/NIAID NIH HHS/United States ; R01 AI078881/AI/NIAID NIH HHS/United States ; R01 AI116868/AI/NIAID NIH HHS/United States ; U19 AI088791/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptation, Physiological/drug effects/genetics ; Antiviral Agents/*therapeutic use ; *Drug Resistance, Viral/drug effects/genetics ; *Hepacivirus/genetics/metabolism ; *Hepatitis C/drug therapy/genetics/metabolism ; Humans ; *Models, Biological ; }, abstract = {RNA viruses exist as a genetically diverse quasispecies with extraordinary ability to adapt to abrupt changes in the host environment. However, the molecular mechanisms that contribute to their rapid adaptation and persistence in vivo are not well studied. Here, we probe hepatitis C virus (HCV) persistence by analyzing clinical samples taken from subjects who were treated with a second-generation HCV protease inhibitor. Frequent longitudinal viral load determinations and large-scale single-genome sequence analyses revealed rapid antiviral resistance development, and surprisingly, dynamic turnover of dominant drug-resistant mutant populations long after treatment cessation. We fitted mathematical models to both the viral load and the viral sequencing data, and the results provided strong support for the critical roles that superinfection and cure of infected cells play in facilitating the rapid turnover and persistence of viral populations. More broadly, our results highlight the importance of considering viral dynamics and competition at the intracellular level in understanding rapid viral adaptation. Thus, we propose a theoretical framework integrating viral and molecular mechanisms to explain rapid viral evolution, resistance, and persistence despite antiviral treatment and host immune responses.}, } @article {pmid29987025, year = {2018}, author = {Santangelo, V and Cavallina, C and Colucci, P and Santori, A and Macrì, S and McGaugh, JL and Campolongo, P}, title = {Enhanced brain activity associated with memory access in highly superior autobiographical memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7795-7800}, pmid = {29987025}, issn = {1091-6490}, mesh = {Adult ; Brain/*diagnostic imaging/*physiology ; *Connectome ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Memory/*physiology ; }, abstract = {Brain systems underlying human memory function have been classically investigated studying patients with selective memory impairments. The discovery of rare individuals who have highly superior autobiographical memory (HSAM) provides, instead, an opportunity to investigate the brain systems underlying enhanced memory. Here, we carried out an fMRI investigation of a group of subjects identified as having HSAM. During fMRI scanning, eight subjects with HSAM and 21 control subjects were asked to retrieve autobiographical memories (AMs) as well as non-AMs (e.g., examples of animals). Subjects were instructed to signal the "access" to an AM by a key press and to continue "reliving" it immediately after. Compared with controls, individuals with HSAM provided a richer AM recollection and were faster in accessing AMs. The access to AMs was associated with enhanced prefrontal/hippocampal functional connectivity. AM access also induced increased activity in the left temporoparietal junction and enhanced functional coupling with sensory cortices in subjects with HSAM compared with controls. In contrast, subjects with HSAM did not differ from controls in functional activity during the reliving phase. These findings, based on fMRI assessment, provide evidence of interaction of brain systems engaged in memory retrieval and suggest that enhanced activity of these systems is selectively involved in enabling more efficient access to past experiences in HSAM.}, } @article {pmid29987024, year = {2018}, author = {He, P and Yang, W}, title = {Template and primer requirements for DNA Pol θ-mediated end joining.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7747-7752}, pmid = {29987024}, issn = {1091-6490}, mesh = {Catalytic Domain ; DNA/biosynthesis/*chemistry/genetics ; *DNA End-Joining Repair ; DNA Primers/*chemistry/genetics/metabolism ; DNA-Directed DNA Polymerase/*chemistry/genetics/metabolism ; HEK293 Cells ; Humans ; }, abstract = {DNA Pol θ-mediated end joining (TMEJ) is a microhomology-based pathway for repairing double-strand breaks in eukaryotes. TMEJ is also a pathway for nonspecific integration of foreign DNAs into host genomes. DNA Pol θ shares structural homology with the high-fidelity replicases, and its polymerase domain (Polθ) has been shown to extend ssDNA without an apparent template. Using oligonucleotides with distinct sequences, we find that with Mg2+ and physiological salt concentrations, human Polθ has no terminal transferase activity and requires a minimum of 2 bp and optimally 4 bp between a template/primer pair for DNA synthesis. Polθ can tolerate a mismatched base pair at the primer end but loses >90% activity when the mismatch is 2 bp upstream from the active site. Polθ is severely inhibited when the template strand has a 3' overhang within 3-4 bp from the active site. In line with its TMEJ function, Polθ has limited strand-displacement activity, and the efficiency and extent of primer extension are similar with or without a downstream duplex.}, } @article {pmid29987023, year = {2018}, author = {Sunamura, S and Satoh, K and Kurosawa, R and Ohtsuki, T and Kikuchi, N and Elias-Al-Mamun, M and Shimizu, T and Ikeda, S and Suzuki, K and Satoh, T and Omura, J and Nogi, M and Numano, K and Siddique, MAH and Miyata, S and Miura, M and Shimokawa, H}, title = {Different roles of myocardial ROCK1 and ROCK2 in cardiac dysfunction and postcapillary pulmonary hypertension in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7129-E7138}, pmid = {29987023}, issn = {1091-6490}, mesh = {Animals ; Basigin/biosynthesis/genetics ; Cardiomegaly/genetics/*metabolism/pathology ; Cyclophilin A/biosynthesis ; Heart Failure/genetics/*metabolism/pathology ; Hypertension, Pulmonary/genetics/*metabolism/pathology ; Lung/*metabolism/pathology ; Mice ; Mice, Knockout ; Myocardium/*metabolism/pathology ; rho-Associated Kinases/genetics/*metabolism ; }, abstract = {Although postcapillary pulmonary hypertension (PH) is an important prognostic factor for patients with heart failure (HF), its pathogenesis remains to be fully elucidated. To elucidate the different roles of Rho-kinase isoforms, ROCK1 and ROCK2, in cardiomyocytes in response to chronic pressure overload, we performed transverse aortic constriction (TAC) in cardiac-specific ROCK1-deficient (cROCK1-/-) and ROCK2-deficient (cROCK2-/-) mice. Cardiomyocyte-specific ROCK1 deficiency promoted pressure-overload-induced cardiac dysfunction and postcapillary PH, whereas cardiomyocyte-specific ROCK2 deficiency showed opposite results. Histological analysis showed that pressure-overload-induced cardiac hypertrophy and fibrosis were enhanced in cROCK1-/- mice compared with controls, whereas cardiac hypertrophy was attenuated in cROCK2-/- mice after TAC. Consistently, the levels of oxidative stress were up-regulated in cROCK1-/- hearts and down-regulated in cROCK2-/- hearts compared with controls after TAC. Furthermore, cyclophilin A (CyPA) and basigin (Bsg), both of which augment oxidative stress, enhanced cardiac dysfunction and postcapillary PH in cROCK1-/- mice, whereas their expressions were significantly lower in cROCK2-/- mice. In clinical studies, plasma levels of CyPA were significantly increased in HF patients and were higher in patients with postcapillary PH compared with those without it. Finally, high-throughput screening demonstrated that celastrol, an antioxidant and antiinflammatory agent, reduced the expressions of CyPA and Bsg in the heart and the lung, ameliorating cardiac dysfunction and postcapillary PH induced by TAC. Thus, by differentially affecting CyPA and Bsg expressions, ROCK1 protects and ROCK2 jeopardizes the heart from pressure-overload HF with postcapillary PH, for which celastrol may be a promising agent.}, } @article {pmid29987022, year = {2018}, author = {}, title = {Retraction for Ganesh et al., Structure of vaccinia complement protein in complex with heparin and potential implications for complement regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6965}, doi = {10.1073/pnas.1806429115}, pmid = {29987022}, issn = {1091-6490}, } @article {pmid29987021, year = {2018}, author = {Banerjee, S and Ji, C and Mayfield, JE and Goel, A and Xiao, J and Dixon, JE and Guo, X}, title = {Ancient drug curcumin impedes 26S proteasome activity by direct inhibition of dual-specificity tyrosine-regulated kinase 2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8155-8160}, pmid = {29987021}, issn = {1091-6490}, support = {R01 DK018024/DK/NIDDK NIH HHS/United States ; R01 DK018849/DK/NIDDK NIH HHS/United States ; R37 DK018024/DK/NIDDK NIH HHS/United States ; T32 CA009523/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology/therapeutic use ; Apoptosis/drug effects ; CRISPR-Cas Systems ; Cell Proliferation/drug effects ; Crystallography, X-Ray ; Curcumin/*pharmacology/therapeutic use ; Drug Synergism ; Female ; Gene Editing/methods ; Gene Knockout Techniques/methods ; HEK293 Cells ; Humans ; Inhibitory Concentration 50 ; Mice ; Neoplasms/*drug therapy/pathology ; Oligopeptides/pharmacology ; Proteasome Endopeptidase Complex/*metabolism ; Proteasome Inhibitors/pharmacology ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/chemistry/genetics/metabolism ; Protein-Tyrosine Kinases/*antagonists & inhibitors/chemistry/genetics/metabolism ; Signal Transduction/drug effects ; Tumor Burden/drug effects ; Xenograft Model Antitumor Assays ; }, abstract = {Curcumin, the active ingredient in Curcuma longa, has been in medicinal use since ancient times. However, the therapeutic targets and signaling cascades modulated by curcumin have been enigmatic despite extensive research. Here we identify dual-specificity tyrosine-regulated kinase 2 (DYRK2), a positive regulator of the 26S proteasome, as a direct target of curcumin. Curcumin occupies the ATP-binding pocket of DYRK2 in the cocrystal structure, and it potently and specifically inhibits DYRK2 over 139 other kinases tested in vitro. As a result, curcumin diminishes DYRK2-mediated 26S proteasome phosphorylation in cells, leading to reduced proteasome activity and impaired cell proliferation. Interestingly, curcumin synergizes with the therapeutic proteasome inhibitor carfilzomib to induce apoptosis in a variety of proteasome-addicted cancer cells, while this drug combination exhibits modest to no cytotoxicity to noncancerous cells. In a breast cancer xenograft model, curcumin treatment significantly reduces tumor burden in immunocompromised mice, showing a similar antitumor effect as CRISPR/Cas9-mediated DYRK2 depletion. These results reveal an unexpected role of curcumin in DYRK2-proteasome inhibition and provide a proof-of-concept that pharmacological manipulation of proteasome regulators may offer new opportunities for anticancer treatment.}, } @article {pmid29987020, year = {2018}, author = {He, J and Xia, M and Yeung, PKK and Li, J and Li, Z and Chung, KK and Chung, SK and Xia, J}, title = {PICK1 inhibits the E3 ubiquitin ligase activity of Parkin and reduces its neuronal protective effect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7193-E7201}, pmid = {29987020}, issn = {1091-6490}, mesh = {Animals ; Carrier Proteins/genetics/*metabolism ; Cell Line, Tumor ; MPTP Poisoning/genetics/*metabolism/pathology ; Mice ; Mice, Knockout ; Nuclear Proteins/genetics/*metabolism ; Protein Domains ; Ubiquitin-Protein Ligases/genetics/*metabolism ; }, abstract = {Parkin functions as a multipurpose E3 ubiquitin ligase, and Parkin loss of function is associated with both sporadic and familial Parkinson's disease (PD). We report that the Bin/Amphiphysin/Rvs (BAR) domain of protein interacting with PRKCA1 (PICK1) bound to the really interesting new gene 1 (RING1) domain of Parkin and potently inhibited the E3 ligase activity of Parkin by disrupting its interaction with UbcH7. Parkin translocated to damaged mitochondria and led to their degradation in neurons, whereas PICK1 robustly inhibited this process. PICK1 also impaired the protective function of Parkin against stresses in SH-SY5Y cells and neurons. The protein levels of several Parkin substrates were reduced in young PICK1-knockout mice, and these mice were resistant to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-mediated toxicity. Taken together, the results indicate that PICK1 is a potent inhibitor of Parkin, and the reduction of PICK1 enhances the protective effect of Parkin.}, } @article {pmid29987019, year = {2018}, author = {Wang, Q and Phillips, NE and Small, ML and Sampson, RJ}, title = {Urban mobility and neighborhood isolation in America's 50 largest cities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7735-7740}, pmid = {29987019}, issn = {1091-6490}, mesh = {Female ; Humans ; Male ; *Models, Theoretical ; *Population Dynamics ; *Social Media ; United States ; *Urban Population ; *Urban Renewal ; }, abstract = {Influential research on the negative effects of living in a disadvantaged neighborhood assumes that its residents are socially isolated from nonpoor or "mainstream" neighborhoods, but the extent and nature of such isolation remain in question. We develop a test of neighborhood isolation that improves on static measures derived from commonly used census reports by leveraging fine-grained dynamic data on the everyday movement of residents in America's 50 largest cities. We analyze 650 million geocoded Twitter messages to estimate the home locations and travel patterns of almost 400,000 residents over 18 mo. We find surprisingly high consistency across neighborhoods of different race and income characteristics in the average travel distance (radius) and number of neighborhoods traveled to (spread) in the metropolitan region; however, we uncover notable differences in the composition of the neighborhoods visited. Residents of primarily black and Hispanic neighborhoods-whether poor or not-are far less exposed to either nonpoor or white middle-class neighborhoods than residents of primarily white neighborhoods. These large racial differences are notable given recent declines in segregation and the increasing diversity of American cities. We also find that white poor neighborhoods are substantially isolated from nonpoor white neighborhoods. The results suggest that even though residents of disadvantaged neighborhoods travel far and wide, their relative isolation and segregation persist.}, } @article {pmid29987018, year = {2018}, author = {Hudait, A and Moberg, DR and Qiu, Y and Odendahl, N and Paesani, F and Molinero, V}, title = {Preordering of water is not needed for ice recognition by hyperactive antifreeze proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {8266-8271}, pmid = {29987018}, issn = {1091-6490}, mesh = {Antifreeze Proteins/*chemistry ; Binding Sites ; *Ice ; Spectrophotometry, Infrared ; Spectrum Analysis, Raman ; Water/*chemistry ; }, abstract = {Antifreeze proteins (AFPs) inhibit ice growth in organisms living in cold environments. Hyperactive insect AFPs are particularly effective, binding ice through "anchored clathrate" motifs. It has been hypothesized that the binding of hyperactive AFPs to ice is facilitated by preordering of water at the ice-binding site (IBS) of the protein in solution. The antifreeze protein TmAFP displays the best matching of its binding site to ice, making it the optimal candidate to develop ice-like order in solution. Here we use multiresolution simulations to unravel the mechanism by which TmAFP recognizes and binds ice. We find that water at the IBS of the antifreeze protein in solution does not acquire ice-like or anchored clathrate-like order. Ice recognition occurs by slow diffusion of the protein to achieve the proper orientation with respect to the ice surface, followed by fast collective organization of the hydration water at the IBS to form an anchored clathrate motif that latches the protein to the ice surface. The simulations suggest that anchored clathrate order could develop on the large ice-binding surfaces of aggregates of ice-nucleating proteins (INP). We compute the infrared and Raman spectra of water in the anchored clathrate motif. The signatures of the OH stretch of water in the anchored clathrate motif can be distinguished from those of bulk liquid in the Raman spectra, but not in the infrared spectra. We thus suggest that Raman spectroscopy may be used to probe the anchored clathrate order at the ice-binding surface of INP aggregates.}, } @article {pmid29987017, year = {2018}, author = {Di Pierro, M and Potoyan, DA and Wolynes, PG and Onuchic, JN}, title = {Anomalous diffusion, spatial coherence, and viscoelasticity from the energy landscape of human chromosomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7753-7758}, pmid = {29987017}, issn = {1091-6490}, mesh = {Chromosomes, Human/*metabolism ; Elasticity ; Epigenesis, Genetic/*physiology ; Genetic Markers ; *Genome, Human ; Humans ; Interphase/*physiology ; *Models, Biological ; Viscosity ; }, abstract = {The nucleus of a eukaryotic cell is a nonequilibrium system where chromatin is subjected to active processes that continuously rearrange it over the cell's life cycle. Tracking the motion of chromosomal loci provides information about the organization of the genome and the physical processes shaping that organization. Optical experiments report that loci move with subdiffusive dynamics and that there is spatially coherent motion of the chromatin. We recently showed that it is possible to predict the 3D architecture of genomes through a physical model for chromosomes that accounts for the biochemical interactions mediated by proteins and regulated by epigenetic markers through a transferable energy landscape. Here, we study the temporal dynamics generated by this quasi-equilibrium energy landscape assuming Langevin dynamics at an effective temperature. Using molecular dynamics simulations of two interacting human chromosomes, we show that the very same interactions that account for genome architecture naturally reproduce the spatial coherence, viscoelasticity, and the subdiffusive behavior of the motion in interphase chromosomes as observed in numerous experiments. The agreement between theory and experiments suggests that even if active processes are involved, an effective quasi-equilibrium landscape model can largely mimic their dynamical effects.}, } @article {pmid29987016, year = {2018}, author = {Seersholm, FV and Cole, TL and Grealy, A and Rawlence, NJ and Greig, K and Knapp, M and Stat, M and Hansen, AJ and Easton, LJ and Shepherd, L and Tennyson, AJD and Scofield, RP and Walter, R and Bunce, M}, title = {Subsistence practices, past biodiversity, and anthropogenic impacts revealed by New Zealand-wide ancient DNA survey.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7771-7776}, pmid = {29987016}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; *Bone and Bones ; DNA/chemistry/*genetics/isolation & purification ; *Fossils ; *Gene Pool ; New Zealand ; }, abstract = {New Zealand's geographic isolation, lack of native terrestrial mammals, and Gondwanan origins make it an ideal location to study evolutionary processes. However, since the archipelago was first settled by humans 750 y ago, its unique biodiversity has been under pressure, and today an estimated 49% of the terrestrial avifauna is extinct. Current efforts to conserve the remaining fauna rely on a better understanding of the composition of past ecosystems, as well as the causes and timing of past extinctions. The exact temporal and spatial dynamics of New Zealand's extinct fauna, however, can be difficult to interpret, as only a small proportion of animals are preserved as morphologically identifiable fossils. Here, we conduct a large-scale genetic survey of subfossil bone assemblages to elucidate the impact of humans on the environment in New Zealand. By genetically identifying more than 5,000 nondiagnostic bone fragments from archaeological and paleontological sites, we reconstruct a rich faunal record of 110 species of birds, fish, reptiles, amphibians, and marine mammals. We report evidence of five whale species rarely reported from New Zealand archaeological middens and characterize extinct lineages of leiopelmatid frog (Leiopelma sp.) and kākāpō (Strigops habroptilus) haplotypes lost from the gene pool. Taken together, this molecular audit of New Zealand's subfossil record not only contributes to our understanding of past biodiversity and precontact Māori subsistence practices but also provides a more nuanced snapshot of anthropogenic impacts on native fauna after first human arrival.}, } @article {pmid29987015, year = {2018}, author = {Tummala, H and Dokal, AD and Walne, A and Ellison, A and Cardoso, S and Amirthasigamanipillai, S and Kirwan, M and Browne, I and Sidhu, JK and Rajeeve, V and Rio-Machin, A and Seraihi, AA and Duncombe, AS and Jenner, M and Smith, OP and Enright, H and Norton, A and Aksu, T and Özbek, NY and Pontikos, N and Cutillas, P and Dokal, I and Vulliamy, T}, title = {Genome instability is a consequence of transcription deficiency in patients with bone marrow failure harboring biallelic ERCC6L2 variants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7777-7782}, pmid = {29987015}, issn = {1091-6490}, support = {MR/P018440//Medical Research Council/United Kingdom ; }, mesh = {A549 Cells ; *Alleles ; Bone Marrow Diseases/genetics/*metabolism/pathology ; DNA Helicases/genetics/*metabolism ; *DNA Repair ; DNA-Activated Protein Kinase/genetics/metabolism ; Female ; Genetic Diseases, Inborn/genetics/*metabolism/pathology ; *Genomic Instability ; HeLa Cells ; Humans ; Male ; RNA Polymerase II/genetics/metabolism ; Syndrome ; *Transcription, Genetic ; }, abstract = {Biallelic variants in the ERCC excision repair 6 like 2 gene (ERCC6L2) are known to cause bone marrow failure (BMF) due to defects in DNA repair and mitochondrial function. Here, we report on eight cases of BMF from five families harboring biallelic variants in ERCC6L2, two of whom present with myelodysplasia. We confirm that ERCC6L2 patients' lymphoblastoid cell lines (LCLs) are hypersensitive to DNA-damaging agents that specifically activate the transcription coupled nucleotide excision repair (TCNER) pathway. Interestingly, patients' LCLs are also hypersensitive to transcription inhibitors that interfere with RNA polymerase II (RNA Pol II) and display an abnormal delay in transcription recovery. Using affinity-based mass spectrometry we found that ERCC6L2 interacts with DNA-dependent protein kinase (DNA-PK), a regulatory component of the RNA Pol II transcription complex. Chromatin immunoprecipitation PCR studies revealed ERCC6L2 occupancy on gene bodies along with RNA Pol II and DNA-PK. Patients' LCLs fail to terminate transcript elongation accurately upon DNA damage and display a significant increase in nuclear DNA-RNA hybrids (R loops). Collectively, we conclude that ERCC6L2 is involved in regulating RNA Pol II-mediated transcription via its interaction with DNA-PK to resolve R loops and minimize transcription-associated genome instability. The inherited BMF syndrome caused by biallelic variants in ERCC6L2 can be considered as a primary transcription deficiency rather than a DNA repair defect.}, } @article {pmid29987014, year = {2018}, author = {Meriin, AB and Narayanan, A and Meng, L and Alexandrov, I and Varelas, X and Cissé, II and Sherman, MY}, title = {Hsp70-Bag3 complex is a hub for proteotoxicity-induced signaling that controls protein aggregation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7043-E7052}, pmid = {29987014}, issn = {1091-6490}, support = {R01 CA176326/CA/NCI NIH HHS/United States ; R01 HL124392/HL/NHLBI NIH HHS/United States ; UL1 TR001430/TR/NCATS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Apoptosis Regulatory Proteins/genetics/*metabolism ; HSP70 Heat-Shock Proteins/genetics/*metabolism ; HeLa Cells ; Humans ; Multiprotein Complexes/genetics/*metabolism ; Protein Aggregation, Pathological/genetics/*metabolism/pathology ; Proteostasis Deficiencies/genetics/*metabolism/pathology ; *Signal Transduction ; }, abstract = {Protein abnormalities in cells are the cause of major pathologies, and a number of adaptive responses have evolved to relieve the toxicity of misfolded polypeptides. To trigger these responses, cells must detect the buildup of aberrant proteins which often associate with proteasome failure, but the sensing mechanism is poorly understood. Here we demonstrate that this mechanism involves the heat shock protein 70-Bcl-2-associated athanogene 3 (Hsp70-Bag3) complex, which upon proteasome suppression responds to the accumulation of defective ribosomal products, preferentially recognizing the stalled polypeptides. Components of the ribosome quality control system LTN1 and VCP and the ribosome-associated chaperone NAC are necessary for the interaction of these species with the Hsp70-Bag3 complex. This complex regulates important signaling pathways, including the Hippo pathway effectors LATS1/2 and the p38 and JNK stress kinases. Furthermore, under proteotoxic stress Hsp70-Bag3-LATS1/2 signaling regulates protein aggregation. We established that the regulated step was the emergence and growth of abnormal protein oligomers containing only a few molecules, indicating that aggregation is regulated at very early stages. The Hsp70-Bag3 complex therefore functions as an important signaling node that senses proteotoxicity and triggers multiple pathways that control cell physiology, including activation of protein aggregation.}, } @article {pmid29987013, year = {2018}, author = {Belsky, DW and Domingue, BW and Wedow, R and Arseneault, L and Boardman, JD and Caspi, A and Conley, D and Fletcher, JM and Freese, J and Herd, P and Moffitt, TE and Poulton, R and Sicinski, K and Wertz, J and Harris, KM}, title = {Genetic analysis of social-class mobility in five longitudinal studies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7275-E7284}, pmid = {29987013}, issn = {1091-6490}, support = {RC4 AG039029/AG/NIA NIH HHS/United States ; R24 AG045061/AG/NIA NIH HHS/United States ; R01 AG041868/AG/NIA NIH HHS/United States ; P01 HD031921/HD/NICHD NIH HHS/United States ; U01 AG009740/AG/NIA NIH HHS/United States ; R01 HD060726/HD/NICHD NIH HHS/United States ; R01 HD077482/HD/NICHD NIH HHS/United States ; R01 HD073342/HD/NICHD NIH HHS/United States ; G1002190//Medical Research Council/United Kingdom ; P30 AG017266/AG/NIA NIH HHS/United States ; MR/P005918/1//Medical Research Council/United Kingdom ; P30 AG028716/AG/NIA NIH HHS/United States ; RC2 AG036495/AG/NIA NIH HHS/United States ; R01 AG032282/AG/NIA NIH HHS/United States ; }, mesh = {Educational Status ; Genetic Testing ; *Genome-Wide Association Study ; Humans ; Longitudinal Studies ; Occupations ; Siblings ; *Social Class ; *Social Mobility ; }, abstract = {A summary genetic measure, called a "polygenic score," derived from a genome-wide association study (GWAS) of education can modestly predict a person's educational and economic success. This prediction could signal a biological mechanism: Education-linked genetics could encode characteristics that help people get ahead in life. Alternatively, prediction could reflect social history: People from well-off families might stay well-off for social reasons, and these families might also look alike genetically. A key test to distinguish biological mechanism from social history is if people with higher education polygenic scores tend to climb the social ladder beyond their parents' position. Upward mobility would indicate education-linked genetics encodes characteristics that foster success. We tested if education-linked polygenic scores predicted social mobility in >20,000 individuals in five longitudinal studies in the United States, Britain, and New Zealand. Participants with higher polygenic scores achieved more education and career success and accumulated more wealth. However, they also tended to come from better-off families. In the key test, participants with higher polygenic scores tended to be upwardly mobile compared with their parents. Moreover, in sibling-difference analysis, the sibling with the higher polygenic score was more upwardly mobile. Thus, education GWAS discoveries are not mere correlates of privilege; they influence social mobility within a life. Additional analyses revealed that a mother's polygenic score predicted her child's attainment over and above the child's own polygenic score, suggesting parents' genetics can also affect their children's attainment through environmental pathways. Education GWAS discoveries affect socioeconomic attainment through influence on individuals' family-of-origin environments and their social mobility.}, } @article {pmid29987012, year = {2018}, author = {Procházková, M and Füzik, T and Škubník, K and Moravcová, J and Ubiparip, Z and Přidal, A and Plevka, P}, title = {Virion structure and genome delivery mechanism of sacbrood honeybee virus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7759-7764}, pmid = {29987012}, issn = {1091-6490}, mesh = {Animals ; Bees/*virology ; *Capsid Proteins/chemistry/metabolism ; Crystallography, X-Ray ; Endosomes/chemistry/metabolism/*virology ; *Genome, Viral ; *RNA Viruses/chemistry/metabolism ; *Virion/chemistry/metabolism ; }, abstract = {Infection by sacbrood virus (SBV) from the family Iflaviridae is lethal to honey bee larvae but only rarely causes the collapse of honey bee colonies. Despite the negative effect of SBV on honey bees, the structure of its particles and mechanism of its genome delivery are unknown. Here we present the crystal structure of SBV virion and show that it contains 60 copies of a minor capsid protein (MiCP) attached to the virion surface. No similar MiCPs have been previously reported in any of the related viruses from the order Picornavirales. The location of the MiCP coding sequence within the SBV genome indicates that the MiCP evolved from a C-terminal extension of a major capsid protein by the introduction of a cleavage site for a virus protease. The exposure of SBV to acidic pH, which the virus likely encounters during cell entry, induces the formation of pores at threefold and fivefold axes of the capsid that are 7 Å and 12 Å in diameter, respectively. This is in contrast to vertebrate picornaviruses, in which the pores along twofold icosahedral symmetry axes are currently considered the most likely sites for genome release. SBV virions lack VP4 subunits that facilitate the genome delivery of many related dicistroviruses and picornaviruses. MiCP subunits induce liposome disruption in vitro, indicating that they are functional analogs of VP4 subunits and enable the virus genome to escape across the endosome membrane into the cell cytoplasm.}, } @article {pmid29987011, year = {2018}, author = {Sellers, PJ and Schimel, DS and Moore, B and Liu, J and Eldering, A}, title = {Observing carbon cycle-climate feedbacks from space.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7860-7868}, pmid = {29987011}, issn = {1091-6490}, abstract = {The impact of human emissions of carbon dioxide and methane on climate is an accepted central concern for current society. It is increasingly evident that atmospheric concentrations of carbon dioxide and methane are not simply a function of emissions but that there are myriad feedbacks forced by changes in climate that affect atmospheric concentrations. If these feedbacks change with changing climate, which is likely, then the effect of the human enterprise on climate will change. Quantifying, understanding, and articulating the feedbacks within the carbon-climate system at the process level are crucial if we are to employ Earth system models to inform effective mitigation regimes that would lead to a stable climate. Recent advances using space-based, more highly resolved measurements of carbon exchange and its component processes-photosynthesis, respiration, and biomass burning-suggest that remote sensing can add key spatial and process resolution to the existing in situ systems needed to provide enhanced understanding and advancements in Earth system models. Information about emissions and feedbacks from a long-term carbon-climate observing system is essential to better stewardship of the planet.}, } @article {pmid29987010, year = {2018}, author = {Koehler, MC and Buick, R and Kipp, MA and Stüeken, EE and Zaloumis, J}, title = {Transient surface ocean oxygenation recorded in the ∼2.66-Ga Jeerinah Formation, Australia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7711-7716}, pmid = {29987010}, issn = {1091-6490}, mesh = {Australia ; *Models, Chemical ; Nitrogen Isotopes/*chemistry ; *Oceans and Seas ; Oxidation-Reduction ; Oxygen/*chemistry ; }, abstract = {Many paleoredox proxies indicate low-level and dynamic incipient oxygenation of Earth's surface environments during the Neoarchean (2.8-2.5 Ga) before the Great Oxidation Event (GOE) at ∼2.4 Ga. The mode, tempo, and scale of these redox changes are poorly understood, because data from various locations and ages suggest both protracted and transient oxygenation. Here, we present bulk rock and kerogen-bound nitrogen isotope ratios as well as bulk rock selenium abundances and isotope ratios from drill cores sampled at high stratigraphic resolution through the Jeerinah Formation (∼2.66 Ga; Fortescue Group, Western Australia) to test for changes in the redox state of the surface environment. We find that both shallow and deep depositional facies in the Jeerinah Formation display episodes of positive primary δ15N values ranging from +4 to +6‰, recording aerobic nitrogen cycling that requires free O2 in the upper water column. Moderate selenium enrichments up to 5.4 ppm in the near-shore core may indicate coincident oxidative weathering of sulfide minerals on land, although not to the extent seen in the younger Mt. McRae Shale that records a well-documented "whiff" of atmospheric oxygen at 2.5 Ga. Unlike the Mt. McRae Shale, Jeerinah selenium isotopes do not show a significant excursion concurrent with the positive δ15N values. Our data are thus most parsimoniously interpreted as evidence for transient surface ocean oxygenation lasting less than 50 My, extending over hundreds of kilometers, and occurring well before the GOE. The nitrogen isotope data clearly record nitrification and denitrification, providing the oldest firm evidence for these microbial metabolisms.}, } @article {pmid29987009, year = {2018}, author = {Piecuch, CG and Bittermann, K and Kemp, AC and Ponte, RM and Little, CM and Engelhart, SE and Lentz, SJ}, title = {River-discharge effects on United States Atlantic and Gulf coast sea-level changes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7729-7734}, pmid = {29987009}, issn = {1091-6490}, abstract = {Identifying physical processes responsible for historical coastal sea-level changes is important for anticipating future impacts. Recent studies sought to understand the drivers of interannual to multidecadal sea-level changes on the United States Atlantic and Gulf coasts. Ocean dynamics, terrestrial water storage, vertical land motion, and melting of land ice were highlighted as important mechanisms of sea-level change along this densely populated coast on these time scales. While known to exert an important control on coastal ocean circulation, variable river discharge has been absent from recent discussions of drivers of sea-level change. We update calculations from the 1970s, comparing annual river-discharge and coastal sea-level data along the Gulf of Maine, Mid-Atlantic Bight, South Atlantic Bight, and Gulf of Mexico during 1910-2017. We show that river-discharge and sea-level changes are significantly correlated ([Formula: see text]), such that sea level rises between 0.01 and 0.08 cm for a 1 [Formula: see text] annual river-discharge increase, depending on region. We formulate a theory that describes the relation between river-discharge and halosteric sea-level changes (i.e., changes in sea level related to salinity) as a function of river discharge, Earth's rotation, and density stratification. This theory correctly predicts the order of observed increment sea-level change per unit river-discharge anomaly, suggesting a causal relation. Our results have implications for remote sensing, climate modeling, interpreting Common Era proxy sea-level reconstructions, and projecting coastal flood risk.}, } @article {pmid29987008, year = {2018}, author = {Koch, E and Baig, F and Zaidi, Q}, title = {Picture perception reveals mental geometry of 3D scene inferences.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7807-7812}, pmid = {29987008}, issn = {1091-6490}, support = {R01 EY007556/EY/NEI NIH HHS/United States ; R01 EY013312/EY/NEI NIH HHS/United States ; }, mesh = {Distance Perception/*physiology ; Female ; Humans ; Male ; Retina/*physiology ; Visual Perception/*physiology ; }, abstract = {Pose estimation of objects in real scenes is critically important for biological and machine visual systems, but little is known of how humans infer 3D poses from 2D retinal images. We show unexpectedly remarkable agreement in the 3D poses different observers estimate from pictures. We further show that all observers apply the same inferential rule from all viewpoints, utilizing the geometrically derived back-transform from retinal images to actual 3D scenes. Pose estimations are altered by a fronto-parallel bias, and by image distortions that appear to tilt the ground plane. We used pictures of single sticks or pairs of joined sticks taken from different camera angles. Observers viewed these from five directions, and matched the perceived pose of each stick by rotating an arrow on a horizontal touchscreen. The projection of each 3D stick to the 2D picture, and then onto the retina, is described by an invertible trigonometric expression. The inverted expression yields the back-projection for each object pose, camera elevation, and observer viewpoint. We show that a model that uses the back-projection, modulated by just two free parameters, explains 560 pose estimates per observer. By considering changes in retinal image orientations due to position and elevation of limbs, the model also explains perceived limb poses in a complex scene of two bodies lying on the ground. The inferential rules simply explain both perceptual invariance and dramatic distortions in poses of real and pictured objects, and show the benefits of incorporating projective geometry of light into mental inferences about 3D scenes.}, } @article {pmid29987007, year = {2018}, author = {Cheng, C and Tan, JC and Hahn, MW and Besansky, NJ}, title = {Systems genetic analysis of inversion polymorphisms in the malaria mosquito Anopheles gambiae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7005-E7014}, pmid = {29987007}, issn = {1091-6490}, support = {R01 AI076584/AI/NIAID NIH HHS/United States ; R01 AI125360/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; Anopheles/*genetics ; *Chromosome Inversion ; Chromosomes, Insect/*genetics ; Female ; Male ; *Quantitative Trait, Heritable ; *Transcriptome ; }, abstract = {Inversion polymorphisms in the African malaria vector Anopheles gambiae segregate along climatic gradients of aridity. Despite indirect evidence of their adaptive significance, little is known of the phenotypic targets of selection or the underlying genetic mechanisms. Here we adopt a systems genetics approach to explore the interaction of two inversions on opposite arms of chromosome 2 with gender, climatic conditions, and one another. We measure organismal traits and transcriptional profiles in 8-d-old adults of both sexes and four alternative homokaryotypic classes reared under two alternative climatic regimes. We show that karyotype strongly influences both organismal traits and transcriptional profiles but that the strength and direction of the effects depend upon complex interactions with gender and environmental conditions and between inversions on independent arms. Our data support the suppressed recombination model for the role of inversions in local adaptation, and-supported by transcriptional and physiological measurements following perturbation with the drug rapamycin-suggest that one mechanism underlying their adaptive role may be the maintenance of energy homeostasis.}, } @article {pmid29987006, year = {2018}, author = {Hagan, J and McCarthy, B and Herda, D and Cann Chandrasekher, A}, title = {Dual-process theory of racial isolation, legal cynicism, and reported crime.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7190-7199}, pmid = {29987006}, issn = {1091-6490}, mesh = {*African Americans ; *Crime/legislation & jurisprudence/prevention & control ; *Emergency Medical Dispatch ; Female ; Humans ; Male ; *Racism ; }, abstract = {Why is neighborhood racial composition linked so strongly to police-reported crime? Common explanations include over-policing and negative interactions with police, but police reports of crime are heavily dependent on resident 911 calls. Using Sampson's concept of legal cynicism and Vaisey's dual-process theory, we theorize that racial concentration and isolation consciously and nonconsciously influence neighborhood variation in 911 calls for protection and prevention. The data we analyze are consistent with this thesis. Independent of police reports of crime, we find that neighborhood racial segregation in 1990 and the legal cynicism about crime prevention and protection it engenders have lasting effects on 911 calls more than a decade later, in 2006-2008. Our theory explains this persistent predictive influence through continuity and change in intervening factors. A source of cumulative continuity, the intensification of neighborhood racial concentration and isolation between 1990 and 2000, predicts 911 calls. Likewise, sources of change-heightened neighborhood incarceration and home foreclosures during the financial crisis in 2006-2008-also predict these calls. Our findings are consistent with legal cynicism theory's focus on neighborhood disadvantage, racial isolation, and concerns about police protection and crime prevention; they correspond less with the emphasis of procedural justice theory on police legitimacy.}, } @article {pmid29987005, year = {2018}, author = {Bowie, LE and Maiuri, T and Alpaugh, M and Gabriel, M and Arbez, N and Galleguillos, D and Hung, CLK and Patel, S and Xia, J and Hertz, NT and Ross, CA and Litchfield, DW and Sipione, S and Truant, R}, title = {N6-Furfuryladenine is protective in Huntington's disease models by signaling huntingtin phosphorylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7081-E7090}, pmid = {29987005}, issn = {1091-6490}, support = {MOP-119391//CIHR/Canada ; }, mesh = {*Adenine/analogs & derivatives/pharmacokinetics/pharmacology ; Adenine Phosphoribosyltransferase/genetics/metabolism ; Animals ; Casein Kinase II/genetics/metabolism ; Cell Line, Transformed ; DNA Adducts/genetics/*metabolism ; *DNA Damage ; Disease Models, Animal ; Humans ; Huntington Disease/*drug therapy/genetics/metabolism/pathology ; Mice ; Mice, Transgenic ; Neurons/*metabolism/pathology ; Phosphorylation/drug effects/genetics ; Signal Transduction/*drug effects/genetics ; }, abstract = {The huntingtin N17 domain is a modulator of mutant huntingtin toxicity and is hypophosphorylated in Huntington's disease (HD). We conducted high-content analysis to find compounds that could restore N17 phosphorylation. One lead compound from this screen was N6-furfuryladenine (N6FFA). N6FFA was protective in HD model neurons, and N6FFA treatment of an HD mouse model corrects HD phenotypes and eliminates cortical mutant huntingtin inclusions. We show that N6FFA restores N17 phosphorylation levels by being salvaged to a triphosphate form by adenine phosphoribosyltransferase (APRT) and used as a phosphate donor by casein kinase 2 (CK2). N6FFA is a naturally occurring product of oxidative DNA damage. Phosphorylated huntingtin functionally redistributes and colocalizes with CK2, APRT, and N6FFA DNA adducts at sites of induced DNA damage. We present a model in which this natural product compound is salvaged to provide a triphosphate substrate to signal huntingtin phosphorylation via CK2 during low-ATP stress under conditions of DNA damage, with protective effects in HD model systems.}, } @article {pmid29986764, year = {2018}, author = {Su, JQ and An, XL and Li, B and Chen, QL and Gillings, MR and Chen, H and Zhang, T and Zhu, YG}, title = {Correction to: Metagenomics of urban sewage identifies an extensively shared antibiotic resistome in China.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {127}, pmid = {29986764}, issn = {2049-2618}, abstract = {Unfortunately, after publication of this article [1], it was noticed that the accession numbers for the study were missing. The correct numbers are PRJNA438554, SRP148953.}, } @article {pmid29986754, year = {2018}, author = {Njim, T and Mbanga, C and Mouemba, D and Makebe, H and Toukam, L and Kika, B and Mulango, I}, title = {Determinants of burnout syndrome among nursing students in Cameroon: cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {450}, pmid = {29986754}, issn = {1756-0500}, mesh = {*Burnout, Professional ; Cameroon ; Cross-Sectional Studies ; Female ; Humans ; Male ; Students, Nursing/*psychology ; Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Burnout syndrome defined as a state of emotional exhaustion and disengagement; which could reduce optimal healthcare delivery, is relatively common amongst healthcare trainees. We sought to assess the determinants of burnout syndrome amongst nursing students in Cameroon. A cross-sectional study which included 447 nursing students recruited after written informed consent by convenience sampling, was carried out from January to April 2018. A printed self-administered questionnaire assessing burnout using the OLdenburg Burnout Inventory was used. Multivariable linear regression was used to identify independent determinants of burnout syndrome.

RESULTS: Most (81.17%) of the students were female with the average for disengagement items being 17.10 ± 3.09 (minimum = 8, maximum = 26) and 20.94 ± 3.04 (minimum = 13, maximum = 31) for exhaustion items. After multivariable linear regression analysis, satisfaction with results (RC: - 1.42, 95% CI - 2.52, - 0.32, p value: 0.012) and regret of choice of nursing studies (RC: 2.13, 95% CI 0.58, 3.68, p value = 0.007) were found to be independent predictors of burnout in these students. Early identification of these determinants is required to prevent progression to burnout.}, } @article {pmid29986751, year = {2018}, author = {AlKhalifah, N and Campbell, DA and Falcon, CM and Gardiner, JM and Miller, ND and Romay, MC and Walls, R and Walton, R and Yeh, CT and Bohn, M and Bubert, J and Buckler, ES and Ciampitti, I and Flint-Garcia, S and Gore, MA and Graham, C and Hirsch, C and Holland, JB and Hooker, D and Kaeppler, S and Knoll, J and Lauter, N and Lee, EC and Lorenz, A and Lynch, JP and Moose, SP and Murray, SC and Nelson, R and Rocheford, T and Rodriguez, O and Schnable, JC and Scully, B and Smith, M and Springer, N and Thomison, P and Tuinstra, M and Wisser, RJ and Xu, W and Ertl, D and Schnable, PS and De Leon, N and Spalding, EP and Edwards, J and Lawrence-Dill, CJ}, title = {Maize Genomes to Fields: 2014 and 2015 field season genotype, phenotype, environment, and inbred ear image datasets.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {452}, pmid = {29986751}, issn = {1756-0500}, support = {DBI-0735191//National Science Foundation/ ; DBI-1265383//National Science Foundation/ ; 2011-67003-30342//USDA-NIFA/ ; }, mesh = {*Datasets as Topic ; Environment ; Genome, Plant ; *Genotype ; Inbreeding ; *Phenotype ; Plant Breeding ; Seasons ; Sequence Analysis, DNA ; Zea mays/*genetics ; }, abstract = {OBJECTIVES: Crop improvement relies on analysis of phenotypic, genotypic, and environmental data. Given large, well-integrated, multi-year datasets, diverse queries can be made: Which lines perform best in hot, dry environments? Which alleles of specific genes are required for optimal performance in each environment? Such datasets also can be leveraged to predict cultivar performance, even in uncharacterized environments. The maize Genomes to Fields (G2F) Initiative is a multi-institutional organization of scientists working to generate and analyze such datasets from existing, publicly available inbred lines and hybrids. G2F's genotype by environment project has released 2014 and 2015 datasets to the public, with 2016 and 2017 collected and soon to be made available.

DATA DESCRIPTION: Datasets include DNA sequences; traditional phenotype descriptions, as well as detailed ear, cob, and kernel phenotypes quantified by image analysis; weather station measurements; and soil characterizations by site. Data are released as comma separated value spreadsheets accompanied by extensive README text descriptions. For genotypic and phenotypic data, both raw data and a version with outliers removed are reported. For weather data, two versions are reported: a full dataset calibrated against nearby National Weather Service sites and a second calibrated set with outliers and apparent artifacts removed.}, } @article {pmid29986749, year = {2018}, author = {Amougou, MA and Atangana, PJA and Afouba, AGN and Moundipa, PF and Pineau, P and Njouom, R}, title = {Dichotomous associations of liver pathology with hepatocellular carcinoma morphology in Middle Africa: the situation in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {451}, pmid = {29986749}, issn = {1756-0500}, mesh = {Adult ; Cameroon ; Carcinoma, Hepatocellular/*pathology ; Female ; Humans ; Liver/injuries ; Liver Cirrhosis/pathology ; Liver Neoplasms/*pathology ; Male ; Middle Aged ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: This study evaluates the occurrence of the various morphological subtypes of hepatocellular carcinoma (HCC) and their connections with some risk factors in Cameroonian patients. The database of the 360 liver biopsies received and associated medical records were reviewed for histological and demographic analysis. Archival formalin-fixed and paraffin embedded liver biopsy specimens or slide were re-evaluated in malignancies patients. HCC classification was determined according to the World Health Organization criteria.

RESULTS: Malignancies were confirmed in 24.7% (89/360) of liver biopsies. Primary liver tumors consisted in 80 cases of HCC and one case of hepatoblastoma. The distribution of the morphological variants of HCC was trabecular pattern (n = 45/80, 56.25%), acinar/pseudoglandular (32.5%) or scirrhous (11.2%). Remarkably, liver steatosis was present in 60.0% (48/80) of patients with HCC, most of them infected with hepatitis C virus (75.8%). Well-differentiated trabecular tumors were significantly associated with important fibrotic and necro-inflammatory activities in livers (P = 0.008) whereas acinar pattern was more frequent on fatty livers (P = 0.02). Our finding indicates that in Middle Africa the morphology of HCC subtypes correlates with changes affecting non-tumor liver tissue. Trabecular subtype is installed by strong liver injury whereas acinar pattern is more often associated with lipid metabolism defects.}, } @article {pmid29986748, year = {2018}, author = {Arivan, R and Deepanjali, S}, title = {Prevalence and risk factors of gastro-esophageal reflux disease among undergraduate medical students from a southern Indian medical school: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {448}, pmid = {29986748}, issn = {1756-0500}, mesh = {Cross-Sectional Studies ; Female ; Gastroesophageal Reflux/*epidemiology ; Humans ; India/epidemiology ; Male ; Prevalence ; Risk Factors ; Schools, Medical ; *Students, Medical ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Gastro-esophageal reflux disease (GERD) affects all age groups, and various lifestyle as well as psychological factors are recognized as risk factors for GERD. Undergraduate medical students are exposed to lifestyle changes and psychological stressors. We aimed to study the prevalence of GERD among undergraduate students of a medical school in southern India in a cross-sectional survey using a validated symptom score.

RESULTS: A total of 358 undergraduate medical students participated in the study. There were 188 (52.5%) males and 170 (47.4%) females; the mean (SD) age of the participants was 20.3 (1.5) years. A total of 115 (31.2%) participants had at least one episode of heartburn per week, while 108 (30.1%) participants had at least one episode of regurgitation per week. Heartburn or regurgitation of at least mild severity was present in 115 (32.1%) and 108 (30.16%) of participants respectively. Based on the symptom score, a diagnosis of GERD was made in 18 (5.02%) students. Frequent consumption of carbonated drinks (OR = 3.63 [95% CI 1.39-9.5]; P = 0.008) and frequent consumption of tea or coffee (OR = 4.65 [95% CI 1.2-17.96]; P = 0.026) were significantly associated with a diagnosis of GERD.}, } @article {pmid29986746, year = {2018}, author = {Amin, FZ and Yamashita, T and Ohneda, O}, title = {Deterioration of alveolar development in mice with both HIF-3α knockout and HIF-2α knockdown.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {449}, pmid = {29986746}, issn = {1756-0500}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors ; Endothelial Cells ; Hypoxia-Inducible Factor 1, alpha Subunit ; Mice ; Mice, Inbred C57BL ; *Mice, Knockout ; Pulmonary Alveoli/*growth & development ; Transcription Factors/*genetics ; Vascular Endothelial Growth Factor A ; }, abstract = {OBJECTIVE: Earlier studies from our group using hypoxia-inducible factor 3α knockout mice showed impairments in lung remodeling and lung endothelial cells. Another research from our group demonstrated that impaired expression of hypoxia-inducible factor 2α induced compensatory expression of hypoxia-inducible factor 1α in hypoxia-inducible factor 2α knockdown mice. The present study uncovers more insights by extending the investigation, utilizing mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown.

RESULTS: No mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown died immediately after birth. The mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown exhibited impaired alveolar sacs and lung alveolar structure and decreased endothelial cell numbers. Analysis of relative mRNA expression revealed depressed expressions of hypoxia-inducible factor 1α, vascular cell adhesion molecule 1, vascular endothelial cadherin, angiopoietin 2, Tie-2, and vascular endothelial growth factor in the lungs of mice with both hypoxia-inducible factor 3α knockout and hypoxia-inducible factor 2α knockdown compared to that in wild-type mice. Further analysis is needed to elucidate the impaired development occurred in the lung endothelial cells.}, } @article {pmid29986740, year = {2018}, author = {Asmare, G and Berhan, N and Berhanu, M and Alebel, A}, title = {Determinants of low birth weight among neonates born in Amhara Regional State Referral Hospitals of Ethiopia: unmatched case control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {447}, pmid = {29986740}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Case-Control Studies ; Ethiopia ; Female ; Humans ; Infant ; *Infant, Low Birth Weight ; Infant, Newborn ; Male ; *Maternal Health ; Parturition ; Pregnancy ; Referral and Consultation ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: This study was conducted to identify the determinants of low birth weight among infants born in Amhara Regional State Referral Hospitals of Ethiopia.

RESULTS: This study found that mothers who delivered female infants (AOR: 1.7, 95% CI 1.1, 2.6), occurrence of health problems during current pregnancy (AOR: 2.8, 95% CI 1.7,4.5), absence of antenatal care (AOR: 2.3,95% CI 1.3,4.0), lack of iron supplementation (AOR: 2.8, 95% CI 1.6,4.9), maternal MUAC below 23 cm (AOR: 1.7, 95% CI 1.0,2.7), and gestational age below 37 completed weeks (AOR: 3.3; 95% CI 1.9, 5.7) were found to be determinants of low birth weight.}, } @article {pmid29986704, year = {2018}, author = {Liu, Q and Bi, L and Song, G and Wang, Q and Jin, G}, title = {Species-habitat associations in an old-growth temperate forest in northeastern China.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {20}, pmid = {29986704}, issn = {1472-6785}, support = {31730015//National Natural Science Foundation of China/International ; XDB31000000//Strategic Priority Research Program of the Chinese Academy of Sciences/International ; 2572017EA02//Fundamental Research Funds for the Central Universities/International ; }, abstract = {BACKGROUND: Species coexistence mechanisms and maintenance of biodiversity have long been considered important components of community ecology research. As one of the important mechanisms, species coexistence theory based on niche differentiation has received attention in past years. Thus, topography, through the formation of habitat heterogeneity, affects species distributions and coexistence. A 30-ha dynamic plot of mixed broadleaved-Korean pine (Pinus koraiensis) forest is located in the Heilongjiang Fenglin National Nature Reserve. We examined species-habitat associations using the torus-translation method. We aim to understand the habitat associations of different species, life forms (shrubs, trees), and shade tolerance (light-demanding, midtolerant, shade-tolerant) across life stages (sapling, juvenile and mature), providing further evidence for the role of niche theory in temperate forests.

RESULTS: Of the 33 species we tested, 28 species (84.8%) were at least significantly associated with one habitat type. Positive associations were more frequent in the valley and slope (shady and sunny) and less frequent on the ridge. Thirty-four significant positive associations with the five habitats were detected at three life stages (11, 11 and 12 at the sapling stage, juvenile stage, and mature stage, respectively). The trees were positively associated with the valley, and the shrubs were positively associated with sunny and ridge. The majority of species' habitat preferences shifted among different life stages; the exceptions were Corylus mandshurica, Maackia amurensis, Quercus mongolica, Picea jezoensis and Acer ukurunduense, which had consistent associations with the same habitat at all stages. The midtolerant trees and midtolerant shrubs were positively correlated with sunny across the three life stages.

CONCLUSIONS: Most species show habitat preferences in the plot. These results indicate that niche theory plays an important role in species coexistence. Most species have no consistent association with habitat at different life stages.}, } @article {pmid29986667, year = {2018}, author = {Fiedler, JD and Lanzatella, C and Edmé, SJ and Palmer, NA and Sarath, G and Mitchell, R and Tobias, CM}, title = {Genomic prediction accuracy for switchgrass traits related to bioenergy within differentiated populations.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {142}, pmid = {29986667}, issn = {1471-2229}, support = {DE-AI02-09ER64829//Biological and Environmental Research/ ; 2030-21000-023//Agricultural Research Service/ ; 5440-21000-030//Agricultural Research Service/ ; }, abstract = {BACKGROUND: Switchgrass breeders need to improve the rates of genetic gain in many bioenergy-related traits in order to create improved cultivars that are higher yielding and have optimal biomass composition. One way to achieve this is through genomic selection. However, the heritability of traits needs to be determined as well as the accuracy of prediction in order to determine if efficient selection is possible.

RESULTS: Using five distinct switchgrass populations comprised of three lowland, one upland and one hybrid accession, the accuracy of genomic predictions under different cross-validation strategies and prediction methods was investigated. Individual genotypes were collected using GBS while kin-BLUP, partial least squares, sparse partial least squares, and BayesB methods were employed to predict yield, morphological, and NIRS-based compositional data collected in 2012-2013 from a replicated Nebraska field trial. Population structure was assessed by F statistics which ranged from 0.3952 between lowland and upland accessions to 0.0131 among the lowland accessions. Prediction accuracy ranged from 0.57-0.52 for cell wall soluble glucose and fructose respectively, to insignificant for traits with low repeatability. Ratios of heritability across to within-population ranged from 15 to 0.6.

CONCLUSIONS: Accuracy was significantly affected by both cross-validation strategy and trait. Accounting for population structure with a cross-validation strategy constrained by accession resulted in accuracies that were 69% lower than apparent accuracies using unconstrained cross-validation. Less accurate genomic selection is anticipated when most of the phenotypic variation exists between populations such as with spring regreening and yield phenotypes.}, } @article {pmid29986664, year = {2018}, author = {Heyman, G and Vulić, I and Moens, MF}, title = {A deep learning approach to bilingual lexicon induction in the biomedical domain.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {259}, pmid = {29986664}, issn = {1471-2105}, abstract = {BACKGROUND: Bilingual lexicon induction (BLI) is an important task in the biomedical domain as translation resources are usually available for general language usage, but are often lacking in domain-specific settings. In this article we consider BLI as a classification problem and train a neural network composed of a combination of recurrent long short-term memory and deep feed-forward networks in order to obtain word-level and character-level representations.

RESULTS: The results show that the word-level and character-level representations each improve state-of-the-art results for BLI and biomedical translation mining. The best results are obtained by exploiting the synergy between these word-level and character-level representations in the classification model. We evaluate the models both quantitatively and qualitatively.

CONCLUSIONS: Translation of domain-specific biomedical terminology benefits from the character-level representations compared to relying solely on word-level representations. It is beneficial to take a deep learning approach and learn character-level representations rather than relying on handcrafted representations that are typically used. Our combined model captures the semantics at the word level while also taking into account that specialized terminology often originates from a common root form (e.g., from Greek or Latin).}, } @article {pmid29986660, year = {2018}, author = {Huang, J and Hao, X and Jin, Y and Guo, X and Shao, Q and Kumar, KS and Ahlawat, YK and Harry, DE and Joshi, CP and Zheng, Y}, title = {Temporal transcriptome profiling of developing seeds reveals a concerted gene regulation in relation to oil accumulation in Pongamia (Millettia pinnata).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {140}, pmid = {29986660}, issn = {1471-2229}, support = {31300275//National Natural Science Foundation of China/ ; 31370289//National Natural Science Foundation of China/ ; 2014ZT05S078//Guangdong Innovation Research Team Fund/ ; JCYJ20140724165855348//Research and Development Foundation of Science and Technology of Shenzhen/ ; }, abstract = {BACKGROUND: Pongamia (Millettia pinnata syn. Pongamia pinnata), an oilseed legume species, is emerging as potential feedstock for sustainable biodiesel production. Breeding Pongamia for favorable traits in commercial application will rely on a comprehensive understanding of molecular mechanism regulating oil accumulation during its seed development. To date, only limited genomic or transcript sequences are available for Pongamia, while a temporal transcriptome profiling of developing seeds is still lacking in this species.

RESULTS: In this work, we conducted a time-series analysis of morphological and physiological characters, oil contents and compositions, as well as global gene expression profiles in developing Pongamia seeds. Firstly, three major developmental phases were characterized based on the combined evidences from embryonic shape, seed weight, seed moisture content, and seed color. Then, the gene expression levels at these three phases were quantified by RNA-Seq analyses with three biological replicates from each phase. Nearly 94% of unigenes were expressed at all three phases, whereas only less than 2% of unigenes were exclusively expressed at one of these phases. A total of 8881 differentially expressed genes (DEGs) were identified between phases. Furthermore, the qRT-PCR analyses for 10 DEGs involved in lipid metabolism demonstrated a good reliability of our RNA-Seq data in temporal gene expression profiling. We observed a dramatic increase in seed oil content from the embryogenesis phase to the early seed-filling phase, followed by a steady and moderate increase towards the maximum at the desiccation phase. We proposed that a highly active expression of most genes related to fatty acid (FA) and triacylglycerol (TAG) biosynthesis at the embryogenesis phase might trigger both the substantial oil accumulation and the membrane lipid synthesis for rapid cell proliferation at this phase, while a concerted reactivation of TAG synthesis-related genes at the desiccation phase might further promote storage lipid synthesis to achieve the maximum content of seed oils.

CONCLUSIONS: This study not only built a bridge between gene expression profiles and oil accumulation in developing seeds, but also laid a foundation for future attempts on genetic engineering of Pongamia varieties to acquire higher oil yield or improved oil properties for biofuel applications.}, } @article {pmid29986655, year = {2018}, author = {Lekota, KE and Bezuidt, OKI and Mafofo, J and Rees, J and Muchadeyi, FC and Madoroba, E and van Heerden, H}, title = {Whole genome sequencing and identification of Bacillus endophyticus and B. anthracis isolated from anthrax outbreaks in South Africa.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {67}, pmid = {29986655}, issn = {1471-2180}, abstract = {BACKGROUND: Bacillus endophyticus is a soil plant-endophytic bacterium, while B. anthracis is the causative agent of anthrax. The virulence factors of B. anthracis are the plasmid encoded tripartite toxins (pXO1) and poly-γ-glutamic acid (PGA) capsule (pXO2). B. endophyticus isolated alongside B. anthracis from animals that died of anthrax in Northern Cape Province (NCP), South Africa, harbored polyglutamate genes. The study compared the characteristics of B. anthracis and B. endophyticus with other Bacillus species with a focus on the presence of the PGA capsule or/and unbound PGA. The morphology and whole genome sequence analysis of B. endophyticus strains and B. anthracis were compared.

RESULTS: In conventional microbiology, B. endophyticus showed gram-positive round-shaped rods in single/short chains, which were endospore-forming, non-motile, non-haemolytic with white and dry colonies, and γ-phage resistant. B. anthracis was differentiated from B. endophyticus based on the latter's box-shaped rods in pairs/long chains, white-grey and slimy colonies, encapsulated and γ-phage susceptible. The study identified a PGA polyglutamate synthase operon that consisted of pgsBCA, γ-glutamyltranspeptidase (ggt) and pgsE in B. endophyticus genomes.

CONCLUSIONS: PGA regions of B. anthracis contain capBCADE genes located in the pXO2 required for capsulation formation, while B. endophyticus contain the pgsBCAE genes in the chromosome. Whole genome and microbiology analysis identified B. endophyticus, as a non-capsuled endospore-forming bacterium that consists of PGA required for biosynthesis. B. endophyticus strains do not synthesize surface associated PGA, therefore capsule visualization of B. anthracis is a key diagnostic characteristic. The study highlights the significance of using whole genome shotgun sequencing to identify virulence and other important genes that might be present amongst unknown samples from natural outbreaks. None of the B. anthracis related plasmids or virulence genes were found in the B. endophyticus genomes.}, } @article {pmid29986650, year = {2018}, author = {Ramakrishna, G and Kaur, P and Nigam, D and Chaduvula, PK and Yadav, S and Talukdar, A and Singh, NK and Gaikwad, K}, title = {Genome-wide identification and characterization of InDels and SNPs in Glycine max and Glycine soja for contrasting seed permeability traits.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {141}, pmid = {29986650}, issn = {1471-2229}, abstract = {BACKGROUND: Water permeability governed by seed coat is a major facet of seed crops, especially soybean, whose seeds lack physiological dormancy and experience rapid deterioration in seed viability under prolonged storage. Moreover, the physiological and chemical characteristics of soybean seeds are known to vary with seed coat color. Thus, to underpin the genes controlling water permeability in soybean seeds, we carried out an in-depth characterization of the associated genomic variation.

RESULTS: In the present study, we have analyzed genomic variation between cultivated soybean and its wild progenitor with implications on seed permeability, a trait related to seed storability. Whole genome resequencing of G.max and G. soja, identified SNPs and InDels which were further characterized on the basis of their genomic location and impact on gene expression. Chromosomal density distribution of the variation was assessed across the genome and genes carrying SNPs and InDels were characterized into different metabolic pathways. Seed hardiness is a complex trait that is affected by the allelic constitution of a genetic locus as well as by a tricky web of plant hormone interactions. Seven genes that hold a probable role in the determination of seed permeability were selected and their expression differences at different stages of water imbibition were analyzed. Variant interaction network derived 205 downstream interacting partners of 7 genes confirmed their role in seed related traits. Interestingly, genes encoding for Type I- Inositol polyphosphate 5 phosphatase1 and E3 Ubiquitin ligase could differentiate parental genotypes, revealed protein conformational deformations and were found to segregate among RILs in coherence with their permeability scores. The 2 identified genes, thus showed a preliminary association with the desirable permeability characteristics.

CONCLUSION: In the light of above outcomes, 2 genes were identified that revealed preliminary, but a relevant association with soybean seed permeability trait and hence could serve as a primary material for understanding the molecular pathways controlling seed permeability traits in soybean.}, } @article {pmid29986648, year = {2018}, author = {Pereyre, S and Bénard, C and Brès, C and Le Roy, C and Mauxion, JP and Rideau, F and Sirand-Pugnet, P and Henrich, B and Bébéar, C}, title = {Generation of Mycoplasma hominis gene-targeted mutants by targeting-induced local lesions in genomes (TILLING).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {525}, pmid = {29986648}, issn = {1471-2164}, support = {20030304002FA//Conseil Régional d'Aquitaine/ ; 20040305003FA//Conseil Régional d'Aquitaine/ ; 2003227//European Union FEDER/ ; ANR-10-EQPX-16-01//Investissements d'Avenir/ ; }, mesh = {Adenosine Triphosphatases/metabolism ; Adhesins, Bacterial/genetics ; Bacterial Proteins/*genetics ; Base Pair Mismatch ; Carrier Proteins/*genetics ; Ethyl Methanesulfonate/pharmacology ; Gene Library ; Gene Targeting/*methods ; HeLa Cells ; Humans ; Lipoproteins/*genetics ; Mycoplasma hominis/*genetics/physiology ; Point Mutation/drug effects ; }, abstract = {BACKGROUND: Mycoplasma hominis is a human urogenital pathogen involved in gynaecological, neonatal and extra-genital infections. However, no versatile genetic tools are currently available to study the pathogenicity of this bacterium. Targeting-Induced Local Lesions IN Genomes (TILLING) is a reverse-genetic method that combines point mutations induced by chemical mutagenesis with a DNA screening technique. We used ethyl methanesulfonate (EMS) that introduces C-G to T-A transition mutations to generate a library of M. hominis mutants. As a proof of concept, mutagenized organisms were screened for mutations in two target genes previously associated with the mycoplasma pathogenicity, the vaa gene encoding an adhesin lipoprotein and the oppA gene encoding the main ectoATPase of the bacterium. The resulting mutants were evaluated using functional assays, an adhesion to HeLa cell assay for vaa-mutants and an ATPase activity test for oppA-mutants.

RESULTS: A 1200-clone library was generated by exposing M. hominis PG21 to 9 mg/mL EMS for 3 h. To identify mutants of interest, targeted gene fragments were amplified, heat-denatured, slowly reannealed and digested with the mismatch-specific endonuclease ENDO1. If multiple alleles were present in the PCR amplicons, these alleles formed heteroduplexes during reannealing that were specifically cleaved by ENDO1 at mismatching positions. A total of four vaa-mutants and two oppA-mutants harbouring missense mutations were obtained and fully sequenced. Zero to eight additional mutations were identified in the genomes of each mutant. The vaa-mutants were tested for adhesion to immobilized HeLa cells but their adhesion was not significantly different from the adhesion of M. hominis PG21. One of the two oppA-mutants that were tested for ATPase activity presented a higher affinity for its ATP substrate than the parental strain.

CONCLUSION: For the first time, we demonstrated that M. hominis gene-targeted mutants could be successfully obtained using this TILLING strategy. In the absence of robust genetic tools for studying M. hominis, the TILLING strategy that can target any gene of the genome could help to elucidate gene functions and to better understand the pathogenesis of this human pathogenic species.}, } @article {pmid29986647, year = {2018}, author = {Moisan, S and Levon, S and Cornec-Le Gall, E and Le Meur, Y and Audrézet, MP and Dostie, J and Férec, C}, title = {Novel long-range regulatory mechanisms controlling PKD2 gene expression.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {515}, pmid = {29986647}, issn = {1471-2164}, support = {CIHR MOP-142451//Canadian Institutes of Health Research (CA)/ ; }, mesh = {A549 Cells ; Chromatin/chemistry/*metabolism ; Deoxyribonuclease I/metabolism ; Enhancer Elements, Genetic ; Epithelial Cells/cytology/metabolism ; Gene Expression ; Humans ; Kidney/cytology ; Polycystic Kidney, Autosomal Dominant/*genetics/pathology ; Promoter Regions, Genetic ; TRPP Cation Channels/*genetics/metabolism ; }, abstract = {BACKGROUND: Cis-regulatory elements control gene expression over large distances through the formation of chromatin loops, which allow contact between enhancers and gene promoters. Alterations in cis-acting regulatory systems could be linked to human genetic diseases. Here, we analyse the spatial organization of a large region spanning the polycystic kidney disease 2 (PKD2) gene, one of the genes responsible of autosomal dominant polycystic kidney disease (ADPKD).

RESULTS: By using chromosome conformation capture carbon copy (5C) technology in primary human renal cyst epithelial cells, we identify novel contacts of the PKD2 promoter with chromatin regions, which display characteristics of regulatory elements. In parallel, by using functional analysis with a reporter assay, we demonstrate that three DNAse I hypersensitive sites regions are involved in the regulation of PKD2 gene expression.

CONCLUSIONS: Finally, through alignment of CCCTC-binding factor (CTCF) sites, we suggest that these novel enhancer elements are brought to the PKD2 promoter by chromatin looping via the recruitment of CTCF.}, } @article {pmid29986646, year = {2018}, author = {Minter, EJA and Lowe, CD and Sørensen, MES and Wood, AJ and Cameron, DD and Brockhurst, MA}, title = {Variation and asymmetry in host-symbiont dependence in a microbial symbiosis.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {108}, pmid = {29986646}, issn = {1471-2148}, support = {NE/K011774/2//Natural Environment Research Council/International ; BB/M011151/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; PLP-2014-242//Leverhulme Trust/International ; UF090328//The Royal Society/International ; }, mesh = {Animals ; Chlorella/*physiology ; Chlorophyll/metabolism ; Fluorescence ; Paramecium/growth & development/*microbiology ; Symbiosis/*physiology ; }, abstract = {BACKGROUND: Symbiosis is a major source of evolutionary innovation and, by allowing species to exploit new ecological niches, underpins the functioning of ecosystems. The transition from free-living to obligate symbiosis requires the alignment of the partners' fitness interests and the evolution of mutual dependence. While symbiotic taxa are known to vary widely in the extent of host-symbiont dependence, rather less is known about variation within symbiotic associations.

RESULTS: Using experiments with the microbial symbiosis between the protist Paramecium bursaria and the alga Chlorella, we show variation between pairings in host-symbiont dependence, encompassing facultative associations, mutual dependence and host dependence upon the symbiont. Facultative associations, that is where both the host and the symbiont were capable of free-living growth, displayed higher symbiotic growth rates and higher per host symbiont loads than those with greater degrees of dependence.

CONCLUSIONS: These data show that the Paramecium-Chlorella interaction exists at the boundary between facultative and obligate symbiosis, and further suggest that the host is more likely to evolve dependence than the algal symbiont.}, } @article {pmid29986645, year = {2018}, author = {Carissimo, G and Pain, A and Belda, E and Vernick, KD}, title = {Highly focused transcriptional response of Anopheles coluzzii to O'nyong nyong arbovirus during the primary midgut infection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {526}, pmid = {29986645}, issn = {1471-2164}, support = {AI121587//National Institute of Allergy and Infectious Diseases/ ; 731060 Infravec2//H2020 European Research Council/ ; R21 AI121587/AI/NIAID NIH HHS/United States ; ANR- 10-LABX-62-IBEID//Agence Nationale de la Recherche/ ; 323173 AnoPath//European Research Council/International ; }, mesh = {Animals ; Anopheles/*genetics/metabolism/virology ; Arboviruses/*pathogenicity ; Host-Pathogen Interactions/genetics ; Immunity, Innate/genetics ; Intestinal Mucosa/*metabolism/virology ; MicroRNAs/chemistry/genetics/metabolism ; Principal Component Analysis ; RNA/chemistry/isolation & purification/metabolism ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: Anopheles mosquitoes are efficient vectors of human malaria, but it is unknown why they do not transmit viruses as well as Aedes and Culex mosquitoes. The only arbovirus known to be consistently transmitted by Anopheles mosquitoes is O'nyong nyong virus (ONNV, genus Alphavirus, family Togaviridae). The interaction of Anopheles mosquitoes with RNA viruses has been relatively unexamined.

RESULTS: We transcriptionally profiled the African malaria vector, Anopheles coluzzii, infected with ONNV. Mosquitoes were fed on an infectious bloodmeal and were analyzed by Illumina RNAseq at 3 days post-bloodmeal during the primary virus infection of the midgut epithelium, before systemic dissemination. Virus infection triggers transcriptional regulation of just 30 host candidate genes. Most of the regulated candidate genes are novel, without known function. Of the known genes, a significant cluster includes candidates with predicted involvement in carbohydrate metabolism. Two candidate genes encoding leucine-rich repeat immune (LRIM) factors point to possible involvement of immune protein complexes in the mosquito antiviral response. The primary ONNV infection by bloodmeal shares little transcriptional response in common with ONNV infection by intrathoracic injection, nor with midgut infection by the malaria parasites, Plasmodium falciparum or P. berghei. Profiling of A. coluzzii microRNA (miRNA) identified 118 known miRNAs and 182 potential novel miRNA candidates, with just one miRNA regulated by ONNV infection. This miRNA was not regulated by other previously reported treatments, and may be virus specific. Coexpression analysis of miRNA abundance and messenger RNA expression revealed discrete clusters of genes regulated by Imd and JAK/STAT, immune signaling pathways that are protective against ONNV in the primary infection.

CONCLUSIONS: ONNV infection of the A. coluzzii midgut triggers a remarkably limited gene regulation program of mostly novel candidate genes, which likely includes host genes deployed for antiviral defense, as well as genes manipulated by the virus to facilitate infection. Functional dissection of the ONNV-response candidate genes is expected to generate novel insight into the mechanisms of virus-vector interaction.}, } @article {pmid29986644, year = {2018}, author = {Cologne, J and Loo, L and Shvetsov, YB and Misumi, M and Lin, P and Haiman, CA and Wilkens, LR and Le Marchand, L}, title = {Stepwise approach to SNP-set analysis illustrated with the Metabochip and colorectal cancer in Japanese Americans of the Multiethnic Cohort.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {524}, pmid = {29986644}, issn = {1471-2164}, support = {U01 CA164973/CA/NCI NIH HHS/United States ; U01 HG004802/HG/NHGRI NIH HHS/United States ; U01 CA164973//National Institutes of Health/ ; U01 HG004802//National Institutes of Health/ ; }, mesh = {Asian Americans/*genetics ; Cohort Studies ; Colorectal Neoplasms/ethnology/*genetics/pathology ; Genome-Wide Association Study ; Genotype ; Humans ; Japan ; *Polymorphism, Single Nucleotide ; Receptor, Transforming Growth Factor-beta Type II/genetics/metabolism ; Risk ; Signal Transduction/genetics ; Smad7 Protein/genetics/metabolism ; Transforming Growth Factor beta/genetics/metabolism ; }, abstract = {BACKGROUND: Common variants have explained less than the amount of heritability expected for complex diseases, which has led to interest in less-common variants and more powerful approaches to the analysis of whole-genome scans. Because of low frequency (low statistical power), less-common variants are best analyzed using SNP-set methods such as gene-set or pathway-based analyses. However, there is as yet no clear consensus regarding how to focus in on potential risk variants following set-based analyses. We used a stepwise, telescoping approach to analyze common- and rare-variant data from the Illumina Metabochip array to assess genomic association with colorectal cancer (CRC) in the Japanese sub-population of the Multiethnic Cohort (676 cases, 7180 controls). We started with pathway analysis of SNPs that are in genes and pathways having known mechanistic roles in colorectal cancer, then focused on genes within the pathways that evidenced association with CRC, and finally assessed individual SNPs within the genes that evidenced association. Pathway SNPs downloaded from the dbSNP database were cross-matched with Metabochip SNPs and analyzed using the logistic kernel machine regression approach (logistic SNP-set kernel-machine association test, or sequence kernel association test; SKAT) and related methods.

RESULTS: The TGF-β and WNT pathways were associated with all CRC, and the WNT pathway was associated with colon cancer. Individual genes demonstrating the strongest associations were TGFBR2 in the TGF-β pathway and SMAD7 (which is involved in both the TGF-β and WNT pathways). As partial validation of our approach, a known CRC risk variant in SMAD7 (in both the TGF-β and WNT pathways: rs11874392) was associated with CRC risk in our data. We also detected two novel candidate CRC risk variants (rs13075948 and rs17025857) in TGFBR2, a gene known to be associated with CRC risk.

CONCLUSIONS: A stepwise, telescoping approach identified some potentially novel risk variants associated with colorectal cancer, so it may be a useful method for following up on results of set-based SNP analyses. Further work is required to assess the statistical characteristics of the approach, and additional applications should aid in better clarifying its utility.}, } @article {pmid29986643, year = {2018}, author = {Dahle, G and Quintela, M and Johansen, T and Westgaard, JI and Besnier, F and Aglen, A and Jørstad, KE and Glover, KA}, title = {Analysis of coastal cod (Gadus morhua L.) sampled on spawning sites reveals a genetic gradient throughout Norway's coastline.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {42}, pmid = {29986643}, issn = {1471-2156}, abstract = {BACKGROUND: Atlantic cod (Gadus morhua L.) has formed the basis of many economically significant fisheries in the North Atlantic, and is one of the best studied marine fishes, but a legacy of overexploitation has depleted populations and collapsed fisheries in several regions. Previous studies have identified considerable population genetic structure for Atlantic cod. However, within Norway, which is the country with the largest remaining catch in the Atlantic, the population genetic structure of coastal cod (NCC) along the entire coastline has not yet been investigated. We sampled > 4000 cod from 55 spawning sites. All fish were genotyped with 6 microsatellite markers and Pan I (Dataset 1). A sub-set of the samples (1295 fish from 17 locations) were also genotyped with an additional 9 microsatellites (Dataset 2). Otoliths were read in order to exclude North East Arctic Cod (NEAC) from the analyses, as and where appropriate.

RESULTS: We found no difference in genetic diversity, measured as number of alleles, allelic richness, heterozygosity nor effective population sizes, in the north-south gradient. In both data sets, weak but significant population genetic structure was revealed (Dataset 1: global FST = 0.008, P < 0.0001. Dataset 2: global FST = 0.004, P < 0.0001). While no clear genetic groups were identified, genetic differentiation increased among geographically-distinct samples. Although the locus Gmo132 was identified as a candidate for positive selection, possibly through linkage with a genomic region under selection, overall trends remained when this locus was excluded from the analyses. The most common allele in loci Gmo132 and Gmo34 showed a marked frequency change in the north-south gradient, increasing towards the frequency observed in NEAC in the north.

CONCLUSION: We conclude that Norwegian coastal cod displays significant population genetic structure throughout its entire range, that follows a trend of isolation by distance. Furthermore, we suggest that a gradient of genetic introgression between NEAC and NCC contributes to the observed population genetic structure. The current management regime for coastal cod in Norway, dividing it into two stocks at 62°N, represents a simplification of the level of genetic connectivity among coastal cod in Norway, and needs revision.}, } @article {pmid29986642, year = {2018}, author = {Mekonnen, A and Rueness, EK and Stenseth, NC and Fashing, PJ and Bekele, A and Hernandez-Aguilar, RA and Missbach, R and Haus, T and Zinner, D and Roos, C}, title = {Population genetic structure and evolutionary history of Bale monkeys (Chlorocebus djamdjamensis) in the southern Ethiopian Highlands.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {106}, pmid = {29986642}, issn = {1471-2148}, support = {11727-1//Rufford Small Grants Foundation/International ; }, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Cercopithecus/*genetics ; DNA, Mitochondrial/genetics ; Demography ; *Ecosystem ; Ethiopia ; Genetic Variation ; *Genetics, Population ; Geography ; Haplotypes/genetics ; Phylogeny ; Population Density ; Time Factors ; }, abstract = {BACKGROUND: Species with a restricted geographic distribution, and highly specialized habitat and dietary requirements, are particularly vulnerable to extinction. The Bale monkey (Chlorocebus djamdjamensis) is a little-known arboreal, bamboo-specialist primate endemic to the southern Ethiopian Highlands. While most Bale monkeys inhabit montane forests dominated by bamboo, some occupy forest fragments where bamboo is much less abundant. We used mitochondrial DNA (mtDNA) sequences to analyse the genetic structure and evolutionary history of Bale monkeys covering the majority of their remaining distribution range. We analysed 119 faecal samples from their two main habitats, continuous forest (CF) and fragmented forests (FF), and sequenced 735 bp of the hypervariable region I (HVI) of the control region. We added 12 orthologous sequences from congeneric vervets (C. pygerythrus) and grivets (C. aethiops) as well as animals identified as hybrids, previously collected in southern Ethiopia.

RESULTS: We found strong genetic differentiation (with no shared mtDNA haplotypes) between Bale monkey populations from CF and FF. Phylogenetic analyses revealed two distinct and highly diverged clades: a Bale monkey clade containing only Bale monkeys from CF and a green monkey clade where Bale monkeys from FF cluster with grivets and vervets. Analyses of demographic history revealed that Bale monkey populations (CF and FF) have had stable population sizes over an extended period, but have all recently experienced population declines.

CONCLUSIONS: The pronounced genetic structure and deep mtDNA divergence between Bale monkey populations inhabiting CF and FF are likely to be the results of hybridization and introgression of the FF population with parapatric Chlorocebus species, in contrast to the CF population, which was most likely not impacted by hybridization. Hybridization in the FF population was probably enhanced by an alteration of the bamboo forest habitat towards a more open woodland habitat, which enabled the parapatric Chlorocebus species to invade the Bale monkey's range and introgress the FF population. We therefore propose that the CF and FF Bale monkey populations should be managed as separate units when developing conservation strategies for this threatened species.}, } @article {pmid29986048, year = {2018}, author = {Rey, C and Guéguen, L and Sémon, M and Boussau, B}, title = {Accurate detection of convergent amino-acid evolution with PCOC.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29986048}, issn = {1537-1719}, abstract = {In the history of life, some phenotypes have been acquired several times independently, through convergent evolution. Recently, lots of genome-scale studies have been devoted to identify nucleotides or amino acids that changed in a convergent manner when the convergent phenotypes evolved. These efforts have had mixed results, probably because of differences in the detection methods, and because of conceptual differences about the definition of a convergent substitution. Some methods contend that substitutions are convergent only if they occur on all branches where the phenotype changed towards the exact same state at a given nucleotide or amino acid position. Others are much looser in their requirements and define a convergent substitution as one that leads the site at which they occur to prefer a phylogeny in which species with the convergent phenotype group together. Here we suggest to look for convergent shifts in amino acid preferences instead of convergent substitutions to the exact same amino acid. We define as convergent shifts substitutions that occur on all branches where the phenotype changed and such that they correspond to a change in the type of amino acid preferred at this position. We implement the corresponding model into a method named PCOC. We show on simulations that PCOC better recovers convergent shifts than existing methods in terms of sensitivity and specificity. We test it on a plant protein alignment where convergent evolution has been studied in detail and find that our method recovers several previously identified convergent substitutions and proposes credible new candidates.}, } @article {pmid29986017, year = {2018}, author = {Rogozin, IB and Gertz, EM and Baranov, PV and Poliakov, E and Schaffer, AA}, title = {Genome-Wide Changes in Protein Translation Efficiency Are Associated with Autism.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1902-1919}, pmid = {29986017}, issn = {1759-6653}, mesh = {Algorithms ; Autism Spectrum Disorder/*genetics ; CpG Islands/genetics ; DNA Methylation/genetics ; Evolution, Molecular ; Female ; Gene Regulatory Networks ; *Genome, Human ; Humans ; Male ; Models, Genetic ; Parents ; Polymorphism, Single Nucleotide/genetics ; Protein Biosynthesis/*genetics ; Regression Analysis ; Ribosomes/metabolism ; Selection, Genetic ; Siblings ; }, abstract = {We previously proposed that changes in the efficiency of protein translation are associated with autism spectrum disorders (ASDs). This hypothesis connects environmental factors and genetic factors because each can alter translation efficiency. For genetic factors, we previously tested our hypothesis using a small set of ASD-associated genes, a small set of ASD-associated variants, and a statistic to quantify by how much a single nucleotide variant (SNV) in a protein coding region changes translation speed. In this study, we confirm and extend our hypothesis using a published set of 1,800 autism quartets (parents, one affected child and one unaffected child) and genome-wide variants. Then, we extend the test statistic to combine translation efficiency with other possibly relevant variables: ribosome profiling data, presence/absence of CpG dinucleotides, and phylogenetic conservation. The inclusion of ribosome profiling abundances strengthens our results for male-male sibling pairs. The inclusion of CpG information strengthens our results for female-female pairs, giving an insight into the significant gender differences in autism incidence. By combining the single-variant test statistic for all variants in a gene, we obtain a single gene score to evaluate how well a gene distinguishes between affected and unaffected siblings. Using statistical methods, we compute gene sets that have some power to distinguish between affected and unaffected siblings by translation efficiency of gene variants. Pathway and enrichment analysis of those gene sets suggest the importance of Wnt signaling pathways, some other pathways related to cancer, ATP binding, and ATP-ase pathways in the etiology of ASDs.}, } @article {pmid29986009, year = {2018}, author = {Barton-Owen, TB and Szabó, R and Somorjai, IML and Ferrier, DEK}, title = {A Revised Spiralian Homeobox Gene Classification Incorporating New Polychaete Transcriptomes Reveals a Diverse TALE Class and a Divergent Hox Gene.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2151-2167}, pmid = {29986009}, issn = {1759-6653}, abstract = {The diversity of mechanisms and capacity for regeneration across the Metazoa present an intriguing challenge in evolutionary biology, impacting on the burgeoning field of regenerative medicine. Broad taxonomic sampling is essential to improve our understanding of regeneration, and studies outside of the traditional model organisms have proved extremely informative. Within the historically understudied Spiralia, the Annelida have an impressive variety of tractable regenerative systems. The biomeralizing, blastema-less regeneration of the head appendage (operculum) of the serpulid polychaete keelworm Spirobranchus (formerly Pomatoceros) lamarcki is one such system. To profile potential regulatory mechanisms, we classified the homeobox gene content of opercular regeneration transcriptomes. As a result of retrieving several difficult-to-classify homeobox sequences, we performed an extensive search and phylogenetic analysis of the TALE and PRD-class homeobox gene content of a broad selection of lophotrochozoan genomes. These analyses contribute to our increasing understanding of the diversity, taxonomic extent, rapid evolution, and radical flexibility of these recently discovered homeobox gene radiations. Our expansion and integration of previous nomenclature systems helps to clarify their cryptic orthology. We also describe an unusual divergent S. lamarcki Antp gene, a previously unclassified lophotrochozoan orphan gene family (Lopx), and a number of novel Nk class orphan genes. The expression and potential involvement of many of these lineage- and clade-restricted homeobox genes in S. lamarcki operculum regeneration provides an example of diversity in regenerative mechanisms, as well as significantly improving our understanding of homeobox gene evolution.}, } @article {pmid29986000, year = {2018}, author = {Nozawa, M and Ikeo, K and Gojobori, T}, title = {Gene-by-Gene or Localized Dosage Compensation on the Neo-X Chromosome in Drosophila miranda.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1875-1881}, pmid = {29986000}, issn = {1759-6653}, mesh = {Animals ; *Dosage Compensation, Genetic ; Drosophila/*genetics ; Gene Expression Regulation ; *Genes, Insect ; Genes, X-Linked ; Genes, Y-Linked ; Gonads/metabolism ; Male ; Up-Regulation/genetics ; X Chromosome/*genetics ; }, abstract = {Many organisms have a global mechanism for dosage compensation (DC) operating along the entire male X chromosome, which equalizes gene expression on the male X with that on the two Xs in females and/or on autosomes. At the initial stage of sex chromosome evolution, however, gene-by-gene (or localized) DC may also be necessary because the degeneration of Y-linked genes occurs independently at different times. We therefore tested whether the up-regulation of X-linked genes depends on the status of their Y-linked homologs, using the young sex chromosomes, neo-X and neo-Y, in Drosophila miranda. In support of the presence of gene-by-gene DC, the extent of up-regulation in males was indeed higher for neo-X-linked genes with pseudogenized neo-Y-linked homologs than for neo-X-linked genes with functional neo-Y-linked homologs. Further molecular evolutionary analysis also supports the idea that many individual neo-X-linked genes first acquired the potential for up-regulation, which then enabled the pseudogenization of neo-Y-linked homologs, without serious deleterious effects on male fitness.}, } @article {pmid29985527, year = {2018}, author = {Groth, BR and Huang, Y and Monette, MJ and Pool, JE}, title = {Directional selection reduces developmental canalization against genetic and environmental perturbations in Drosophila wings.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13550}, pmid = {29985527}, issn = {1558-5646}, abstract = {Natural selection may enhance or weaken the robustness of phenotypes against genetic or environmental perturbations. However, important aspects of the relationship between adaptive evolution and canalization remain unclear. Recent work showed that the evolution of larger wing size in a high altitude natural population of Drosophila melanogaster was accompanied by decanalized wing development--specifically a loss of robustness to genetic perturbation. But this study did not address environmental robustness, and it compared populations that may have numerous biological differences. Here, we perform artificial selection on this same trait in D. melanogaster (larger wing length) and directly test whether this directional selection resulted in decanalization. We find that in general, size-selected replicates show greater frequencies of wing defects than control replicates both after mutagenesis (genetic perturbation) and when subjected to high temperature stress (environmental perturbation), although the increase in defect frequency varies importantly among replicates. These results support the hypothesis that directional selection may result in the loss of both genetic and environmental robustness-offering a rare window into the relationship between adaptation and canalization.}, } @article {pmid29985525, year = {2018}, author = {Indermaur, A and Theis, A and Egger, B and Salzburger, W}, title = {Mouth dimorphism in scale-eating cichlid fish from Lake Tanganyika advances individual fitness.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1962-1969}, doi = {10.1111/evo.13552}, pmid = {29985525}, issn = {1558-5646}, support = {156405//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 201067//H2020 European Research Council/ ; 617585//H2020 European Research Council/ ; }, abstract = {Random asymmetry, that is the coexistence of left- and right-sided (or -handed) individuals within a population, is a particular case of natural variation; what triggers and maintains such dimorphisms remains unknown in most cases. Here, we report a field-based cage experiment in the scale-eating Tanganyikan cichlid Perissodus microlepis, which occurs in two morphs in nature: left-skewed and right-skewed individuals with respect to mouth orientation. Using underwater cages stocked with scale-eaters and natural prey fish, we first confirm that, under semi-natural conditions, left-skewed scale-eaters preferentially attack the right flank of their prey, whereas right-skewed individuals feed predominantly from the left side. We then demonstrate that scale-eaters have a higher probability for successful attacks when kept in dimorphic experimental populations (left- and right-skewed morphs together) as compared to monomorphic populations (left- or right-skewed morphs), most likely because prey fishes fail to accustom to strikes from both sides. The significantly increased probability for attacks appears to be the selective agent responsible for the evolution and maintenance of mouth dimorphism in P. microlepis, lending further support to the hypothesis that negative frequency-dependent selection is the stabilizing force balancing the mouth dimorphism at quasi-equal ratios in scale-eating cichlids.}, } @article {pmid29985523, year = {2018}, author = {Becher, H}, title = {Digest: Ancestry mosaics hint at selection and may provide an alternative to differentiation scans.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13549}, pmid = {29985523}, issn = {1558-5646}, abstract = {We now have a flood of genomic sequencing data available to study reproductive isolation and selection in action, but how are these data best analyzed? Usually, genetic differentiation is compared between two groups, scanning along genomes. This approach has several drawbacks, and has been criticized repeatedly. An alternative, truly genetic approach, based on blocks of common ancestry in a hybrid zone setting, is presented by Hvala et al. (2018) in this issue.}, } @article {pmid29985522, year = {2018}, author = {Jiménez-Mena, B and Henriques, R}, title = {Digest: Untangling the influence of soft and hard selection in experimental populations-from environment to genomics.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13548}, pmid = {29985522}, issn = {1558-5646}, abstract = {Gallet et al. (2018) studied the effect of two selection regimes on the maintenance of polymorphism in experimental populations. They took two strains of Escherichia coli, each resistant to a different antibiotic, evolved them in culture conditions representing "soft" or "hard" selective regimes, and measured polymorphism levels for three to five transfers. Their results supported theoretical predictions that only "soft" selection maintains polymorphism, highlighting the importance of experimental studies to understand maintenance of variation in nature.}, } @article {pmid29985124, year = {2018}, author = {de Alvarenga, LV and Vaz, MGMV and Genuário, DB and Esteves-Ferreira, AA and Almeida, AVM and de Castro, NV and Lizieri, C and Souza, JJLL and Schaefer, CEGR and Nunes-Nesi, A and Araújo, WL}, title = {Extending the ecological distribution of Desmonostoc genus: proposal of Desmonostoc salinum sp. nov., a novel Cyanobacteria from a saline-alkaline lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2770-2782}, doi = {10.1099/ijsem.0.002878}, pmid = {29985124}, issn = {1466-5034}, mesh = {Alkalies ; Bacterial Typing Techniques ; Chile ; Cyanobacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Ribosomal Spacer/genetics ; Fatty Acids/chemistry ; Hydrogen-Ion Concentration ; Lakes/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; }, abstract = {Cyanobacteria is an ancient phylum of oxygenic photosynthetic microorganisms found in almost all environments of Earth. In recent years, the taxonomic placement of some cyanobacterial strains, including those belonging to the genus Nostocsensu lato, have been reevaluated by means of a polyphasic approach. Thus, 16S rRNA gene phylogeny and 16S-23S internal transcribed spacer (ITS) secondary structures coupled with morphological, ecological and physiological data are considered powerful tools for a better taxonomic and systematics resolution, leading to the description of novel genera and species. Additionally, underexplored and harsh environments, such as saline-alkaline lakes, have received special attention given they can be a source of novel cyanobacterial taxa. Here, a filamentous heterocytous strain, Nostocaceae CCM-UFV059, isolated from Laguna Amarga, Chile, was characterized applying the polyphasic approach; its fatty acid profile and physiological responses to salt (NaCl) were also determined. Morphologically, this strain was related to morphotypes of the Nostocsensu lato group, being phylogenetically placed into the typical cluster of the genus Desmonostoc. CCM-UFV059 showed identity of the 16S rRNA gene as well as 16S-23S secondary structures that did not match those from known described species of the genus Desmonostoc, as well as distinct ecological and physiological traits. Taken together, these data allowed the description of the first strain of a member of the genus Desmonostoc from a saline-alkaline lake, named Desmonostoc salinum sp. nov., under the provisions of the International Code of Nomenclature for algae, fungi and plants. This finding extends the ecological coverage of the genus Desmonostoc, contributing to a better understanding of cyanobacterial diversity and systematics.}, } @article {pmid29985122, year = {2018}, author = {Wang, Y and Luo, XX and Xia, ZF and Wan, CX and Alim, A and Zhang, LL}, title = {Glycomyces xiaoerkulensis sp. nov., isolated from Xiaoerkule lake in Xinjiang, China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2722-2726}, doi = {10.1099/ijsem.0.002842}, pmid = {29985122}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, strain TRM 41368T, was isolated from a silt sample from Xiaoerkule lake in Xinjiang province, China, and was examined using a polyphasic approach. Strain TRM 41368T was aerobic, Gram-stain-positive, with an optimum NaCl concentration for growth of 5 % (w/v), and an optimum temperature for growth of 35-37 °C. On the basis of 16S rRNA gene sequence analysis, strain TRM 41368T was most closely related to Glycomycesfuscus TRM 49117T (98.46 % similarity). However, it had a relatively low DNA-DNA relatedness value with G. fuscus TRM 49117T (ANI=70.59 %). The organism had chemical and morphological features typical of the genus Glycomyces. The cell wall of TRM 41368T contained meso-diaminopimelic acid; xylose, ribose and glucose were the major whole-cell sugars. The diagnostic polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol and phosphatidylinositolmannosides. The predominant menaquinone was MK-9(H6). The major fatty acids were C18 : 1ω9c, C16 : 0, iso-C16 : 0, anteiso-C17 : 0 and anteiso-C15 : 0. The G+C content of the DNA was 69.9 mol%. On the basis of the polyphasic evidence, strain TRM 41368T should be designated as a novel species of the genus Glycomyces, for which the name Glycomyces xiaoerkulensis sp. nov. is proposed. The type strain is TRM 41368T (=CCTCC AA 2017005T=KCTC 39932T).}, } @article {pmid29984827, year = {2018}, author = {Skwierzyńska, AM and Radwan, J and Plesnar-Bielak, A}, title = {Male-limited secondary sexual trait interacts with environment in determining female fitness.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, pmid = {29984827}, issn = {1558-5646}, abstract = {Selection for secondary sexual trait (SST) elaboration may increase intralocus sexual conflict over the optimal values of traits expressed from shared genomes. This conflict can reduce female fitness, and the resulting gender load can be exacerbated by environmental stress, with consequences for a population's ability to adapt to novel environments. However, how the evolution of SSTs interacts with environment in determining female fitness is not well understood. Here, we investigated this question using replicate lines of bulb mites selected for increased or decreased prevalence of a male SST-thickened legs used as weapons. The fitness of females from these lines was measured at a temperature to which the mites were adapted (24°C), as well as at two novel temperatures: 18°C and 28°C. We found the prevalence of the SST interacted with temperature in determining female fecundity. At 28°C, females from populations with high SST prevalence were less fecund than females from populations in which the SST was rare, but the reverse was true at 18°C. Thus, a novel environment does not universally depress female fitness more in populations with a high degree of sexually selected dimorphism. We discuss possible consequences of the interaction we detected for adaptation to novel environments.}, } @article {pmid29984552, year = {2018}, author = {Gulliver, D and Lipus, D and Ross, D and Bibby, K}, title = {Insights into microbial community structure and function from a shallow, simulated CO2 -leakage aquifer demonstrate microbial selection and adaptation.}, journal = {Environmental microbiology reports}, volume = {}, number = {}, pages = {}, doi = {10.1111/1758-2229.12675}, pmid = {29984552}, issn = {1758-2229}, abstract = {Geological carbon storage is likely to be a part of a comprehensive strategy to minimize the atmospheric release of carbon dioxide (CO2), raising concerns that injected CO2 will leak into overlying freshwater aquifers. CO2(aq) leakage may impact the dominant microbial community responsible for important ecosystem functions such as nutrient cycling, metal cycling and carbon conversion. Here, we examined the impact of an experimental in situ CO2 -leakage on a freshwater aquifer microbial community. High-throughput 16S rRNA gene sequencing demonstrated lower microbial diversity in freshwater wells with CO2 concentrations above 1.15 g l-1 . Metagenomic sequencing and population genome binning were used to evaluate the metabolic potential of microbial populations across four CO2 exposed samples and one control sample. Population genome binning resulted in the recovery and annotation of three metagenome assembled genomes (MAGs). Two of the MAGs, most closely related to Curvibacter and Sulfuricurvum, had the functional capacity for CO2 utilization via carbon fixation coupled to sulfur and iron oxidation. The third draft genome was an Archaea, most closely related to Methanoregula, characterized by the metabolic potential for methanogenesis. Together, these findings show that CO2 leakage in a freshwater aquifer poses a strong selection, driving both microbial community structure and metabolic function.}, } @article {pmid29984543, year = {2018}, author = {Carvalho, F and Sousa, S and Cabanes, D}, title = {l-Rhamnosylation of wall teichoic acids promotes efficient surface association of Listeria monocytogenes virulence factors InlB and Ami through interaction with GW domains.}, journal = {Environmental microbiology}, volume = {20}, number = {11}, pages = {3941-3951}, doi = {10.1111/1462-2920.14351}, pmid = {29984543}, issn = {1462-2920}, abstract = {Wall teichoic acids (WTAs) are important surface glycopolymers involved in various physiological processes occurring in the Gram-positive cell envelope. We previously showed that the decoration of Listeria monocytogenes (Lm) WTAs with l-rhamnose conferred resistance against antimicrobial peptides. Here, we show that WTA l-rhamnosylation also contributes to physiological levels of autolysis in Lm through a mechanism that requires efficient association of Ami, a virulence-promoting autolysin belonging to the GW protein family, to the bacterial cell surface. Importantly, WTA l-rhamnosylation also controls the surface association of another GW protein, the invasin internalin B (InlB), that promotes Lm invasion of host cells. Whereas WTA N-acetylglucosaminylation is not a prerequisite for GW protein surface association, lipoteichoic acids appear to also play a role in the surface anchoring of InlB. Strikingly, while the GW domains of Ami, InlB and Auto (another autolysin contributing to cell invasion and virulence) are sufficient to mediate surface association, this is not the case for the GW domains of the remaining six uncharacterized Lm GW proteins. Overall, we reveal WTA l-rhamnosylation as a bacterial surface modification mechanism that contributes to Lm physiology and pathogenesis by controlling the surface association of GW proteins involved in autolysis and infection.}, } @article {pmid29984466, year = {2018}, author = {Patsch, D and van Vliet, S and Marcantini, LG and Johnson, DR}, title = {Generality of associations between biological richness and the rates of metabolic processes across microbial communities.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4356-4368}, doi = {10.1111/1462-2920.14352}, pmid = {29984466}, issn = {1462-2920}, support = {607492//European Union's Seventh Framework Programme/ ; }, abstract = {Biological richness is positively associated with the rates of some metabolic processes performed by microbial communities. It remains unclear, however, whether these positive associations are a general feature of the metabolic processes performed by microbial communities or whether they are specific to certain types of metabolic processes. For example, it was hypothesized that the strength of any particular positive association depends on how many different genotypes within a microbial community perform the metabolic process of interest (i.e. the 'rarity hypothesis'). We tested the generality of these positive associations by measuring the taxonomic richness, functional gene richness and rate constants for 71 different metabolic processes across 30 independent microbial communities. We found that both taxonomic and functional gene richness do indeed tend to positively associate with the rates of metabolic processes. In addition, we found that positive associations occur across a wide range of different environmental conditions. Counter to the 'rarity hypothesis', however, we did not detect a relationship between the strengths of the positive associations and the rarity of each metabolic process. Together, our data provide empirical evidence that positive associations with biological richness may indeed be a general feature of the metabolic processes performed by microbial communities.}, } @article {pmid29983854, year = {2018}, author = {Haddix, PL and Danderson, CA}, title = {Mutation Rate Simulation by Dice Roll: Practice with the Drake Equation.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983854}, issn = {1935-7877}, } @article {pmid29983853, year = {2018}, author = {Segarra, VA and Wilson, C and Lowery, K and Ransdell, S and Schnuck, J and Way, P and Srougi, MC}, title = {Student-Designed High-Throughput Assays to Assess Effects of Growth Insults in Budding Yeast.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983853}, issn = {1935-7877}, } @article {pmid29983852, year = {2018}, author = {McGuffey, JC and Leon, D and Dhanji, EZ and Mishler, DM and Barrick, JE}, title = {Bacterial Production of Gellan Gum as a Do-It-Yourself Alternative to Agar.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983852}, issn = {1935-7877}, } @article {pmid29983851, year = {2018}, author = {Goff, EE and Reindl, KM and Johnson, C and McClean, P and Offerdahl, EG and Schroeder, NL and White, AR}, title = {Investigation of a Stand-Alone Online Learning Module for Cellular Respiration Instruction.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983851}, issn = {1935-7877}, abstract = {With the recent rise of alternative instructional methodologies such as flipped classrooms and active learning, many core concepts are being introduced outside of the classroom prior to scheduled class meeting times. One popular means for external concept introduction in many undergraduate biology courses is the use of stand-alone online learning modules. Using a group of four large introductory biology course sections, we investigate the use of a stand-alone online learning module developed using animations from Virtual Cell Animation Collection as a resource for the introduction of cellular respiration concepts outside of the classroom. Results from four sections of introductory biology (n = 629) randomized to treatments show that students who interacted with the stand-alone online learning module had significantly higher normalized gain scores on a cellular respiration assessment than students who only attended a traditional lecture as a means of concept introduction (p < 0.001, d = 0.59). These findings suggest a superior ability to convey certain introductory cellular respiration topics in a stand-alone manner outside of the classroom than in a more traditional lecture-based classroom setting.}, } @article {pmid29983850, year = {2018}, author = {Cox, JL and Simpson, MD}, title = {Microbiology Education and Infection Control Competency: Offering a New Perspective.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983850}, issn = {1935-7877}, abstract = {Healthcare-associated infections (HAIs) have become a significant and costly problem for healthcare institutions worldwide. Despite the crucial role of infection prevention and control (IC) procedures, there is a substantial body of evidence to indicate that IC knowledge and practices of health professional graduates is, however, sub-optimal. This paper presents a discussion of the critical role microbiology plays in infection control education and practice, arguing that without an ability to apply microbiology knowledge to IC decision-making, there is an inherent risk of incorrect application of IC practices and thus a risk to patient (and nurse) safety. The authors propose a re-conceptualization of infection control competency, using nursing as an exemplar profession, to reflect practice that is not based on simple memorization of protocols but rather on a sound understanding of microbiology and informed decision-making. The proposal for re-conceptualizing the definition and assessment of IC competence, if adopted, would potentially enhance students' understanding and synthesis of microbiology knowledge and help build students' capacity to apply that knowledge to practice.}, } @article {pmid29983849, year = {2018}, author = {Angra, A and Weigel, E and Onstine, A}, title = {Claw Waving for Sex: An Inquiry-Based Lab to Teach Sexual Dimorphism and Behavior in Fiddler Crabs.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983849}, issn = {1935-7877}, } @article {pmid29983848, year = {2018}, author = {Osueke, B and Mekonnen, B and Stanton, JD}, title = {How Undergraduate Science Students Use Learning Objectives to Study.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983848}, issn = {1935-7877}, abstract = {Learning objectives communicate the knowledge and skills that instructors intend for students to acquire in a course. Student performance can be enhanced when learning objectives align with instruction and assessment. We understand how instructors should use learning objectives, but we know less about how students should use them. We investigated students' use and perceptions of learning objectives in an undergraduate science course at a public research university. In this exploratory study, students (n = 185) completed two open-ended assignments regarding learning objectives and we analyzed the content of their answers. We found that students used learning objectives in ways that reflected the recommendations of past and present instructors, suggesting that students are receptive to instruction on how to use learning objectives. Students generally found learning objectives to be useful because the objectives helped them to narrow their focus and organize their studying, suggesting that students may need additional help from instructors in order to self-direct their learning. Students who chose not to use learning objectives often found other resources, such as case studies covered in class, to be more helpful for their learning. Some of these students recognized that the concepts included in case studies and learning objectives overlapped, pointing to a benefit of alignment between instructional activities and learning objectives. These qualitative results provide the data necessary for designing a quantitative instrument to test the extent to which students' use of learning objectives affects their performance.}, } @article {pmid29983847, year = {2018}, author = {Khan, LB and Swift, S and Kamal, T and Read, HM}, title = {Simulation of MICROBACT Strip Assay Using Colored Liquids to Demonstrate Identification of Unknown Gram-Negative Organisms in Undergraduate Laboratory.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983847}, issn = {1935-7877}, } @article {pmid29983846, year = {2018}, author = {Kiefer, AM and Seney, CS and Lambright, AL and Cottrill, KA and Young, VA}, title = {Makgeolli: Rapid Production of an Alcoholic Beverage from the Fermentation of Rice.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983846}, issn = {1935-7877}, } @article {pmid29983845, year = {2018}, author = {Laungani, R and Tanner, C and Brooks, TD and Clement, B and Clouse, M and Doyle, E and Dworak, S and Elder, B and Marley, K and Schofield, B}, title = {Finding Some Good in an Invasive Species: Introduction and Assessment of a Novel CURE to Improve Experimental Design in Undergraduate Biology Classrooms.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29983845}, issn = {1935-7877}, abstract = {Reports such as Vision and Change in Undergraduate Biology Education call for integration of course-based undergraduate research experiences (CUREs) into biology curricula and less emphasis on "cookbook" laboratories. CUREs, often characterized by a single open-ended research question, allow students to develop hypotheses, design experiments, and collaborate with peers. Conversely, "cookbook" labs incentivize task completion and have pre-determined experimental outcomes. While research comparing CUREs and "cookbook" labs is growing, there are fewer comparisons among CUREs. Here, we present a novel CURE built around an invasive grass, Bromus inermis. We evaluated this CURE's effectiveness in improving students' understanding of the Vision and Change competency relating to the application of the scientific process through development and testing of hypotheses. We did so by comparing changes in pre- and posttest scores on the Experimental Design Ability Test (EDAT) between Brome CURE students and students in a concurrent CURE, SEA-PHAGES. While students in both CUREs showed improvements at the end of the semester, Brome CURE students showed a greater increase in EDAT scores than did SEA-PHAGES CURE students. Additionally, Brome CURE students had significantly higher gains in 6 of the 10 EDAT criteria. We conclude that the Brome CURE is an effective ecological parallel to the SEA-PHAGES CURE and can help students gain a meaningful understanding of Vision and Change competencies. Journal of Microbiology & Biology Education.}, } @article {pmid29983157, year = {2018}, author = {Seymour, RS and Snelling, EP}, title = {Calculating brain perfusion of primates.}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2018.06.001}, pmid = {29983157}, issn = {1095-8606}, } @article {pmid29983156, year = {2018}, author = {García-Martínez, D and Radovčić, D and Radovčić, J and Cofran, Z and Rosas, A and Bastir, M}, title = {Over 100 years of Krapina: New insights into the Neanderthal thorax from the study of rib cross-sectional morphology.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {124-132}, doi = {10.1016/j.jhevol.2018.05.009}, pmid = {29983156}, issn = {1095-8606}, abstract = {The Krapina costal sample was studied by Gorjanović-Kramberger in the early twentieth century. He pointed out unique features in the sample such as the rounder rib cross-section, which was recently confirmed in other Neanderthal specimens. Round rib cross-sections are characteristic of Homo ergaster, suggesting this may be plesiomorphic for Pleistocene Homo, but it is unknown whether Homo antecessor also had this rib shape. Furthermore, the influence of allometry on the cross-sectional shape of ribs is still unknown. The large costal sample from Krapina allows us to address these issues. We quantified cross-section morphology at the midshaft throughout a closed curve of one landmark and nine sliding semilandmarks in the Krapina costal remains (n = 7), as well as in other Neanderthals (n = 50), H. antecessor (n = 3) and modern humans, both fossil (n = 12) and recent (n = 160). We used principal components analysis and mean comparisons to explore interspecific differences, regression analysis to investigate allometry, and partial least squares analysis to examine covariation of cross-section shape and overall rib morphology. Neanderthal cross-sections tended to be larger than those of recent humans except for the Krapina and Tabun remains. Regarding shape, inter-group differences were found only in the diaphragmatic thorax, where Neanderthal and H. antecessor ribs were statistically significantly rounder than those of modern humans. Allometry accounted for covariation of size on shape, but the Neandertal and modern human trajectories had different slopes. While our results based on the Krapina costal sample are similar to previous findings, we also make several new insights: 1) the cross-section morphology observed in Neanderthals was probably present in H. antecessor, albeit less marked; 2) the distinct roundness of Neanderthal cross-sections is not related to size; 3) rounder cross-sections are correlated with ribs presenting less curvature in cranial view and a low degree of torsion in recent humans. These results are important for the interpretation of fragmentary Neanderthal costal remains, and the fact that the differences are marked only in the diaphragmatic thorax could have implications for breathing kinematics.}, } @article {pmid29982935, year = {2018}, author = {Dione, N and Bellali, S and Yasir, M and Azhar, EI and Bibi, F and Beye, M and Armstrong, N and Cadoret, F and Jiman-Fatani, AA and Helmy, N and Rathored, J and Labas, N and Fournier, PE and Raoult, D and Lagier, JC}, title = {Anaerococcus jeddahensis sp. nov., a New Bacterial Species Isolated From Healthy Nomadic Bedouin Woman From Saudi Arabia.}, journal = {Current microbiology}, volume = {75}, number = {11}, pages = {1419-1428}, pmid = {29982935}, issn = {1432-0991}, support = {10-IAHU-03//Fondation Méditerranée Infection/ ; }, mesh = {Base Composition ; Fatty Acids/analysis/metabolism ; Feces/microbiology ; Female ; Firmicutes/classification/genetics/*isolation & purification/metabolism ; Gastrointestinal Microbiome ; Genome, Bacterial ; Humans ; Phylogeny ; Saudi Arabia ; }, abstract = {An understanding of the microbial diversity of the human body has generated significant interest in recent years. With the advent of MALDI-TOF mass spectrometry, high-speed sequencing, and the rebirth of microbial culture, knowledge of human microbiota is growing. Using culturomics, a strategy to explore the microbial diversity of samples, coupled with a taxono-genomic strategy, we isolated a new bacterium named Anaerococcus jeddahensis sp. nov. strain SB3T. This strain was isolated from the stool sample of a healthy nomadic Bedouin woman from Saudi Arabia. Here, we describe the characteristics of this organism, and the complete genome sequence and annotation. Strain SB3T is a Gram-positive obligate anaerobic coccus which is non-motile and non-spore forming. Fatty acid analysis shows that the major fatty acid is by far hexadecanoic acid (C16:0; 52%). Its genome is 1,903,534 bp long and has 29.70 mol% of G+C content. It contains 1756 protein-coding genes and 53 RNA genes. These results show that strategy provides a better understanding of the microorganism and that is a good methodology for microbial identification and characterization.}, } @article {pmid29982603, year = {2018}, author = {Brüggemann, H and Migliorini, LB and Sales, RO and Koga, PCM and Souza, AV and Jensen, A and Poehlein, A and Brzuszkiewicz, E and Doi, AM and Pasternak, J and Martino, MDV and Severino, P}, title = {Comparative Genomics of Nonoutbreak Pseudomonas aeruginosa Strains Underlines Genome Plasticity and Geographic Relatedness of the Global Clone ST235.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1852-1857}, pmid = {29982603}, issn = {1759-6653}, mesh = {Brazil ; Genome, Bacterial ; Humans ; Phylogeny ; Pseudomonas Infections/*microbiology/pathology ; Pseudomonas aeruginosa/*classification/*genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {Pseudomonas aeruginosa is an important opportunistic pathogen in hospitals, responsible for various infections that are difficult to treat due to intrinsic and acquired antibiotic resistance. Here, 20 epidemiologically unrelated strains isolated from patients in a general hospital over a time period of two decades were analyzed using whole genome sequencing. The genomes were compared in order to assess the presence of a predominant clone or sequence type (ST). No clonal structure was identified, but core genome-based single nucleotide polymorphism (SNP) analysis distinguished two major, previously identified phylogenetic groups. Interestingly, most of the older strains isolated between 1994 and 1998 harbored exoU, encoding a cytotoxic phospholipase. In contrast, most strains isolated between 2011 and 2016 were exoU-negative and phylogenetically very distinct from the older strains, suggesting a population shift of nosocomial P. aeruginosa over time. Three out of 20 strains were ST235 strains, a global high-risk clonal lineage; these carried several additional resistance determinants including aac(6')Ib-cr encoding an aminoglycoside N-acetyltransferase that confers resistance to fluoroquinolones. Core genome comparison with ST235 strains from other parts of the world showed that the three strains clustered together with other Brazilian/Argentinean isolates. Despite this regional relatedness, the individuality of each of the three ST235 strains was revealed by core genome-based SNPs and the presence of genomic islands in the accessory genome. Similarly, strain-specific characteristics were detected for the remaining strains, indicative of individual evolutionary histories and elevated genome plasticity.}, } @article {pmid29982569, year = {2018}, author = {Dong, W and Vannozzi, A and Chen, F and Hu, Y and Chen, Z and Zhang, L}, title = {MORC Domain Definition and Evolutionary Analysis of the MORC Gene Family in Green Plants.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1730-1744}, pmid = {29982569}, issn = {1759-6653}, mesh = {Adenosine Triphosphatases/*genetics ; Animals ; Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; Evolution, Molecular ; Gene Duplication ; Gene Expression Regulation, Plant ; *Genes, Plant ; Genome, Plant ; Humans ; Models, Molecular ; *Multigene Family ; *Phylogeny ; Plant Proteins/*genetics ; Transcriptome ; Viridiplantae/*genetics ; }, abstract = {Microrchidia (MORC) proteins have been described as epigenetic regulators and plant immune mediators in Arabidopsis. Typically, plant and animal MORC proteins contain a hallmark GHKL-type (Gyrase, Hsp90, Histidine kinase, MutL) ATPase domain in their N-terminus. Here, 356 and 83 MORC orthologues were identified in 60 plant and 27 animal genomes. Large-scale MORC sequence analyses revealed the presence of a highly conserved motif composition that defined as the MORC domain. The MORC domain was present in both plants and animals, indicating that it originated in the common ancestor before the divergence of plants and animals. Phylogenetic analyses showed that MORC genes in both plant and animal lineages were clearly classified into two major groups, named Plants-Group I, Plants-Group II and Animals-Group I, Animals-Group II, respectively. Further analyses of MORC genes in green plants uncovered that Group I can be subdivided into Group I-1 and Group I-2. Group I-1 only contains seed plant genes, suggesting that Group I-1 and I-2 divergence occurred at least before the emergence of spermatophytes. Group I-2 and Group II have undergone several gene duplications, resulting in the expansion of MORC gene family in angiosperms. Additionally, MORC gene expression analyses in Arabidopsis, soybean, and rice revealed a higher expression level in reproductive tissues compared with other organs, and showed divergent expression patterns for several paralogous gene pairs. Our studies offered new insights into the origins, phylogenetic relationships, and expressional patterns of MORC family members in green plants, which would help to further reveal their functions as plant epigenetic regulators.}, } @article {pmid29982531, year = {2018}, author = {Bisch, G and Neuvonen, MM and Pierce, NE and Russell, JA and Koga, R and Sanders, JG and Lukasik, P and Andersson, SGE}, title = {Genome Evolution of Bartonellaceae Symbionts of Ants at the Opposite Ends of the Trophic Scale.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1687-1704}, pmid = {29982531}, issn = {1759-6653}, mesh = {Animal Nutritional Physiological Phenomena ; Animals ; Ants/anatomy & histology/*microbiology/physiology/ultrastructure ; Bartonellaceae/*genetics/physiology ; *Evolution, Molecular ; Gastrointestinal Microbiome ; Genome Size ; *Genome, Bacterial ; Phylogeny ; Symbiosis ; }, abstract = {Many insects rely on bacterial symbionts to supply essential amino acids and vitamins that are deficient in their diets, but metabolic comparisons of closely related gut bacteria in insects with different dietary preferences have not been performed. Here, we demonstrate that herbivorous ants of the genus Dolichoderus from the Peruvian Amazon host bacteria of the family Bartonellaceae, known for establishing chronic or pathogenic infections in mammals. We detected these bacteria in all studied Dolichoderus species, and found that they reside in the midgut wall, that is, the same location as many previously described nutritional endosymbionts of insects. The genomic analysis of four divergent strains infecting different Dolichoderus species revealed genes encoding pathways for nitrogen recycling and biosynthesis of several vitamins and all essential amino acids. In contrast, several biosynthetic pathways have been lost, whereas genes for the import and conversion of histidine and arginine to glutamine have been retained in the genome of a closely related gut bacterium of the carnivorous ant Harpegnathos saltator. The broad biosynthetic repertoire in Bartonellaceae of herbivorous ants resembled that of gut bacteria of honeybees that likewise feed on carbohydrate-rich diets. Taken together, the broad distribution of Bartonellaceae across Dolichoderus ants, their small genome sizes, the specific location within hosts, and the broad biosynthetic capability suggest that these bacteria are nutritional symbionts in herbivorous ants. The results highlight the important role of the host nutritional biology for the genomic evolution of the gut microbiota-and conversely, the importance of the microbiota for the nutrition of hosts.}, } @article {pmid29982504, year = {2018}, author = {Potts, LD and Perez Calderon, LJ and Gontikaki, E and Keith, L and Gubry-Rangin, C and Anderson, JA and Witte, U}, title = {Effect of spatial origin and hydrocarbon composition on bacterial consortia community structure and hydrocarbon biodegradation rates.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, pmid = {29982504}, issn = {1574-6941}, abstract = {Oil reserves in deep-sea sediments are currently subject to intense exploration, with associated risks of oil spills. Previous research suggests that microbial communities from deep-sea sediment (>1000m) can degrade hydrocarbons (HCs), but have a lower degradation ability than shallow (<200m) communities, probably due to in situ temperature. This study aimed to assess the effect of marine origin on microbial HC degradation potential while separating the influence of temperature, and to characterise associated HC-degrading bacterial communities. Microbial communities from 135 and 1000 m deep sediments were selectively enriched on crude oil at in situ temperatures and both consortia were subsequently incubated for 42 days at 20°C with two HC mixtures: diesel fuel or model oil. Significant HC biodegradation occurred rapidly in the presence of both consortia, especially of low molecular weight HCs and was concomitant with microbial community changes. Further, oil degradation was higher with the shallow consortium than with the deep one. Dominant HC-degrading bacteria differed based on both spatial origin of the consortia and supplemented HC types. This study provides evidence for influence of sediment spatial origin and HC composition on the selection and activity of marine HC-degrading bacterial communities and is relevant for future bioremediationdevelopments.}, } @article {pmid29982460, year = {2018}, author = {Barbosa, R and Pontes, A and Santos, RO and Montandon, GG and de Ponzzes-Gomes, CM and Morais, PB and Gonçalves, P and Rosa, CA and Sampaio, JP}, title = {Multiple Rounds of Artificial Selection Promote Microbe Secondary Domestication-The Case of Cachaça Yeasts.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1939-1955}, pmid = {29982460}, issn = {1759-6653}, mesh = {Aquaporins/genetics ; Base Sequence ; Fermentation/genetics ; Genes, Fungal ; Genetic Variation ; Models, Biological ; Phylogeny ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; *Selection, Genetic ; }, abstract = {The study of microbe domestication has witnessed major advances that contribute to a better understanding of the emergence of artificially selected phenotypes and set the foundations of their rational improvement for biotechnology. Several features make Saccharomyces cerevisiae an ideal model for such a study, notably the availability of a catalogue of signatures of artificial selection and the extensive knowledge available on its biological processes. Here, we investigate with population and comparative genomics a set of strains used for cachaça fermentation, a Brazilian beverage based on the fermentation of sugar cane juice. We ask if the selective pressures posed by this fermentation have given rise to a domesticated lineage distinct from the ones already known, like wine, beer, bread, and sake yeasts. Our results show that cachaça yeasts derive from wine yeasts that have undergone an additional round of domestication, which we define as secondary domestication. As a consequence, cachaça strains combine features of wine yeasts, such as the presence of genes relevant for wine fermentation and advantageous gene inactivations, with features of beer yeasts like resistance to the effects of inhibitory compounds present in molasses. For other markers like those related to sulfite resistance and biotin metabolism our analyses revealed distributions more complex than previously reported that support the secondary domestication hypothesis. We propose a multilayered microbe domestication model encompassing not only transitions from wild to primarily domesticated populations, as in the case of wine yeasts, but also secondary domestications like those of cachaça yeasts.}, } @article {pmid29982456, year = {2018}, author = {Danneels, B and Pinto-Carbó, M and Carlier, A}, title = {Patterns of Nucleotide Deletion and Insertion Inferred from Bacterial Pseudogenes.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1792-1802}, pmid = {29982456}, issn = {1759-6653}, mesh = {Bacteria/*genetics ; DNA Repair ; Evolution, Molecular ; Genome, Bacterial ; *Mutagenesis, Insertional ; Nucleotides/*genetics ; Phylogeny ; *Pseudogenes ; *Sequence Deletion ; }, abstract = {Pseudogenes are a paradigm of neutral evolution and their study has the potential to reveal intrinsic mutational biases. However, this potential is mitigated by the fact that pseudogenes are quickly purged from bacterial genomes. Here, we assembled a large set of pseudogenes from genomes experiencing reductive evolution as well as functional references for which we could establish reliable phylogenetic relationships. Using this unique dataset, we identified 857 independent insertion and deletion mutations and discover a pervasive bias towards deletions, but not insertions, with sizes multiples of 3 nt. We further show that selective constraints for the preservation of gene frame are unlikely to account for the observed mutational bias and propose that a mechanistic bias in alternative end-joining repair, a recombination-independent double strand break DNA repair mechanism, is responsible for the accumulation of 3n deletions.}, } @article {pmid29982435, year = {2018}, author = {Ambrós, S and de la Iglesia, F and Rosario, SM and Butkovic, A and Elena, SF}, title = {Engineered Functional Redundancy Relaxes Selective Constraints upon Endogenous Genes in Viral RNA Genomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1823-1836}, pmid = {29982435}, issn = {1759-6653}, mesh = {*Evolution, Molecular ; *Genome, Viral ; Mutation ; Plant Diseases/*virology ; Plants/*virology ; Potyvirus/*genetics/pathogenicity ; Pseudogenes ; RNA Interference ; RNA Viruses/genetics ; RNA, Viral/*genetics ; }, abstract = {Functional redundancy, understood as the functional overlap of different genes, is a double-edge sword. At the one side, it is thought to serve as a robustness mechanism that buffers the deleterious effect of mutations hitting one of the redundant copies, thus resulting in pseudogenization. At the other side, it is considered as a source of genetic and functional innovation. In any case, genetically redundant genes are expected to show an acceleration in the rate of molecular evolution. Here, we tackle the role of functional redundancy in viral RNA genomes. To this end, we have evaluated the rates of compensatory evolution for deleterious mutations affecting an essential function, the suppression of RNA silencing plant defense, of tobacco etch potyvirus (TEV). TEV genotypes containing deleterious mutations in presence/absence of engineered functional redundancy were evolved and the pattern of fitness and pathogenicity recovery evaluated. Genetically redundant genotypes suffered less from the effect of deleterious mutations and showed relatively minor changes in fitness and pathogenicity. By contrast, nongenetically redundant genotypes had very low fitness and pathogenicity at the beginning of the evolution experiment that were fully recovered by the end. At the molecular level, the outcome depended on the combination of the actual mutations being compensated and the presence/absence of functional redundancy. Reversions to wild-type alleles were the norm in the nonredundant genotypes while redundant ones either did not fix any mutation at all or showed a higher nonsynonymous mutational load.}, } @article {pmid29982428, year = {2018}, author = {Heß, S and Berendonk, TU and Kneis, D}, title = {Antibiotic resistant bacteria and resistance genes in the bottom sediment of a small stream and the potential impact of remobilization.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy128}, pmid = {29982428}, issn = {1574-6941}, abstract = {River sediments are regarded as hot spots of bacterial density and activity. Moreover, high bacterial densities and biofilm formation are known to promote horizontal gene transfer, the latter playing a vital role in the spread of antimicrobial resistance. It can thus be hypothesized that sediments act as a reservoir of antibiotic resistant bacteria (ARB) and resistance genes (ARGs), particularly in rivers receiving microbes and drug residues from treated sewage. We analyzed the phenotypic susceptibility of 782 Escherichia coli isolates against 24 antimicrobials and we measured the relative abundances of five ARGs in water and sediment extracts of a small stream. We did not find evidence for a general increase in the proportion of resistant E. coli isolated from sediments as compared to those found in stream water. For most antimicrobials, the likelihood of detecting a resistant isolate was similar in water and sediment or it was even lower in the latter compartment. The mean relative abundance of ARGs was moderately increased in sediment-borne samples. Generally, absolute abundances of resistant cells and resistance genes in the sediment exceeded the pelagic level owing to higher bacterial densities. The river bottom thus represents a reservoir of ARB and ARGs that can be mobilized by resuspension.}, } @article {pmid29982426, year = {2018}, author = {Bethke, J and Yáñez, AJ and Avendaño-Herrera, R}, title = {Comparative Genomic Analysis of Two Chilean Renibacterium salmoninarum Isolates and the Type Strain ATCC 33209T.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1816-1822}, pmid = {29982426}, issn = {1759-6653}, mesh = {Actinobacteria/*genetics/*isolation & purification ; Animals ; Bacterial Proteins/genetics ; Chile ; Fish Diseases/*microbiology ; *Genome, Bacterial ; Genomics ; Salmonidae/*microbiology ; Virulence Factors/genetics ; }, abstract = {Renibacterium salmoninarum, a slow-growing facultative intracellular pathogen belonging to the high C + G content Actinobacteria phylum, is the causative agent of bacterial kidney disease, a progressive granulomatous infection affecting salmonids worldwide. This Gram-positive bacterium has existed in the Chilean salmonid industry for >30 years, but little or no information is available regarding the virulence mechanisms and genomic characteristics of Chilean isolates. In this study, the genomes of two Chilean isolates (H-2 and DJ2R) were sequenced, and a search was conducted for genes and proteins involved in virulence and pathogenicity, and we compare with the type strain ATCC 33209 T genome. The genome sizes of H-2 and DJ2R are 3,155,332 bp and 3,155,228 bp, respectively. They genomes presented six ribosomal RNA, 46 transcription RNA, and 25 noncodingRNA, and both had the same 56.27% G + C content described for the type strain ATCC 33209 T. A total of 3,522 and 3,527 coding sequences were found for H-2 and DJ2R, respectively. Meanwhile, the ATCC 33209 T type strain had 3,519 coding sequences. The in silico genome analysis revealed a genes related to tricarboxylic acid cycle, glycolysis, iron transport and others metabolic pathway. Also, the data indicated that R salmoninarum may have a variety of possible virulence-factor and antibiotic-resistance strategies. Interestingly, many of genes had high identities with Mycobacterium species, a known pathogenic Actinobacteria bacterium. In summary, this study provides the first insights into and initial steps towards understanding the molecular basis of antibiotic resistance, virulence mechanisms and host/environment adaptation in two Chilean R. salmoninarum isolates that contain proteins of which were similar to those of Mycobacterium. Furthermore, important information is presented that could facilitate the development of preventive and treatment measures against R. salmoninarum in Chile and worldwide.}, } @article {pmid29982420, year = {2018}, author = {Saito, Y and Sato, T and Nomoto, K and Tsuji, H}, title = {Identification of phenol- and p-cresol-producing intestinal bacteria by using media supplemented with tyrosine and its metabolites.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy125}, pmid = {29982420}, issn = {1574-6941}, abstract = {To identify intestinal bacteria that produce phenols (phenol and p-cresol), we screened 153 strains within 152 species in 44 genera by culture-based assay using broth media supplemented with 200 µM each of tyrosine and its predicted microbial metabolic intermediates (4-hydroxyphenylpyruvate, DL-4-hydroxyphenyllactate, 3-(p-hydroxyphenyl)propionate, 4-hydroxyphenylacetate and 4-hydroxybenzoate). Phenol-producing activity was found in 36 strains and p-cresol-producing activity in 55 strains. Sixteen strains had both types of activity. Phylogenetic analysis based on the 16S rRNA gene sequences of strains that produced 100 µM or more of phenols revealed that 16 phenol producers belonged to the Coriobacteriaceae, Enterobacteriaceae, Fusobacteriaceae and Clostridium clusters I and XIVa; four p-cresol-producing bacteria belonged to the Coriobacteriaceae and Clostridium clusters XI and XIVa; and one strain producing both belonged to the Coriobacteriaceae. A genomic search for protein homologs of enzymes involved in the metabolism of tyrosine to phenols in 10 phenol producers and four p-cresol producers, the draft genomes of which were available in public databases, predicted that phenol producers harbored tyrosine phenol-lyase or hydroxyarylic acid decarboxylase, or both, and p-cresol producers harbored p-hydroxyphenylacetate decarboxylase or tyrosine lyase, or both. These results provide important information about the bacterial strains that contribute to production of phenols in the intestine.}, } @article {pmid29982411, year = {2018}, author = {Saad, R and Cohanim, AB and Kosloff, M and Privman, E}, title = {Neofunctionalization in Ligand Binding Sites of Ant Olfactory Receptors.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2490-2500}, pmid = {29982411}, issn = {1759-6653}, abstract = {Chemical communication is fundamental for the operation of insect societies. Their diverse vocabulary of chemical signals requires a correspondingly diverse set of chemosensory receptors. Insect olfactory receptors (ORs) are the largest family of chemosensory receptors. The OR family is characterized by frequent expansions of subfamilies, in which duplicated ORs may adapt to detect new signals through positive selection on their amino acid sequence. Ants are an extreme example with ∼400 ORs per genome-the highest number in insects. Presumably, this reflects an increased complexity of chemical communication. Here, we examined gene duplications and positive selection on ant ORs. We reconstructed the hymenopteran OR gene tree, including five ant species, and inferred positive selection along every branch using the branch-site test, a total of 3326 tests. We find more positive selection in branches following species-specific duplications. We identified amino acid sites targeted by positive selection, and mapped them onto a structural model of insect ORs. Seventeen sites were under positive selection in six or more branches, forming two clusters on the extracellular side of the receptor, on either side of a cleft in the structure. This region was previously implicated in ligand activation, suggesting that the concentration of positively selected sites in this region is related to adaptive evolution of ligand binding sites or allosteric transmission of ligand activation. These results provide insights into the specific OR subfamilies and individual residues that facilitated adaptive evolution of olfactory functions, potentially explaining the elaboration of chemical signaling in ant societies.}, } @article {pmid29982398, year = {2018}, author = {Valdespino-Castillo, PM and Cerqueda-García, D and Espinosa, AC and Batista, S and Merino-Ibarra, M and Tas, N and Alcántara-Hernández, RJ and Falcón, LI}, title = {Microbial distribution and turnover in Antarctic microbial mats highlight the relevance of heterotrophic bacteria in low-nutrient environments.}, journal = {FEMS microbiology ecology}, volume = {}, number = {}, pages = {}, doi = {10.1093/femsec/fiy129}, pmid = {29982398}, issn = {1574-6941}, abstract = {Maritime Antarctica has shown the highest increase in temperature in the Southern Hemisphere. Under this scenario, biogeochemical cycles may be altered, resulting in rapid environmental change for Antarctic biota. Microbes, that drive biogeochemical cycles often form biofilms or microbial mats in continental meltwater environments. Limnetic microbial mats from the Fildes Peninsula were studied using high-throughput 16S rRNA gene sequencing. Mat samples were collected from fifteen meltwater stream sites, comprising a natural gradient from ultraoligotrophic glacier flows to meltwater streams exposed to anthropogenic activities. Our analyses show microbial structure differences between mats are explained by environmental NH4+, NO3-, DIN, soluble reactive silicon and conductivity. Microbial mats living under ultraoligotrophic meltwater conditions did not exhibit a dominance of cyanobacterial photoautotrophs, as it has been documented for other Antarctic limnetic microbial mats. Instead, ultraoligotrophic mat communities were characterized by the presence of microbes recognized as heterotrophs and photoheterotrophs. This suggests that microbial capabilities for recycling may be a key factor to dwell in ultra-low nutrient conditions. Our analyses show that phylotype level assemblages exhibit coupled distribution patterns in environmental oligotrophic inland waters. The evaluation of these microbes suggests the relevance of reproductive and structural strategies to pioneer these psychrophilic ultraoligotrophic environments.}, } @article {pmid29982381, year = {2018}, author = {Vialle, RA and de Souza, JES and Lopes, KP and Teixeira, DG and Alves Sobrinho, PA and Ribeiro-Dos-Santos, AM and Furtado, C and Sakamoto, T and Oliveira Silva, FA and Herculano Corrêa de Oliveira, E and Hamoy, IG and Assumpção, PP and Ribeiro-Dos-Santos, Â and Santos Lima, JPM and Seuánez, HN and de Souza, SJ and Santos, S}, title = {Whole Genome Sequencing of the Pirarucu (Arapaima gigas) Supports Independent Emergence of Major Teleost Clades.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2366-2379}, pmid = {29982381}, issn = {1759-6653}, abstract = {The Pirarucu (Arapaima gigas) is one of the world's largest freshwater fishes and member of the superorder Osteoglossomorpha (bonytongues), one of the oldest lineages of ray-finned fishes. This species is an obligate air-breather found in the basin of the Amazon River with an attractive potential for aquaculture. Its phylogenetic position among bony fishes makes the Pirarucu a relevant subject for evolutionary studies of early teleost diversification. Here, we present, for the first time, a draft genome version of the A. gigas genome, providing useful information for further functional and evolutionary studies. The A. gigas genome was assembled with 103-Gb raw reads sequenced in an Illumina platform. The final draft genome assembly was ∼661 Mb, with a contig N50 equal to 51.23 kb and scaffold N50 of 668 kb. Repeat sequences accounted for 21.69% of the whole genome, and a total of 24,655 protein-coding genes were predicted from the genome assembly, with an average of nine exons per gene. Phylogenomic analysis based on 24 fish species supported the postulation that Osteoglossomorpha and Elopomorpha (eels, tarpons, and bonefishes) are sister groups, both forming a sister lineage with respect to Clupeocephala (remaining teleosts). Divergence time estimations suggested that Osteoglossomorpha and Elopomorpha lineages emerged independently in a period of ∼30 Myr in the Jurassic. The draft genome of A. gigas provides a valuable genetic resource for further investigations of evolutionary studies and may also offer a valuable data for economic applications.}, } @article {pmid29981933, year = {2018}, author = {Ali, H and Muhammad, A and Bala, NS and Wang, G and Chen, Z and Peng, Z and Hou, Y}, title = {Genomic evaluations of Wolbachia and mtDNA in the population of coconut hispine beetle, Brontispa longissima (Coleoptera: Chrysomelidae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {1000-1009}, doi = {10.1016/j.ympev.2018.07.003}, pmid = {29981933}, issn = {1095-9513}, abstract = {Wolbachia pipientis is a diverse, ubiquitous and most prevalent intracellular bacterial group of alpha-Proteobacteria that is concerned with many biological processes in arthropods. The coconut hispine beetle (CHB), Brontispa longissima (Gestro) is an economically important pest of palm cultivation worldwide. In the present study, we comprehensively surveyed the Wolbachia-infection prevalence and mitochondrial DNA (mtDNA) polymorphism in CHB from five different geographical locations, including China's Mainland and Taiwan, Vietnam, Thailand, Malaysia and Indonesia. A total of 540 sequences were screened in this study through three different genes, i.e., cytochrome oxidase subunit I (COI), Wolbachia outer surface protein (wsp) and multilocus sequencing type (MLST) genes. The COI genetic divergence ranges from 0.08% to 0.67%, and likewise, a significant genetic diversity (π = 0.00082; P = 0.049) was noted within and between all analyzed samples. In the meantime, ten different haplotypes (H) were characterized (haplotype diversity = 0.4379) from 21 different locations, and among them, H6 (46 individuals) have shown a maximum number of population clusters than others. Subsequently, Wolbachia-prevalence results indicated that all tested specimens of CHB were found positive (100%), which suggested that CHB was naturally infected with Wolbachia. Wolbachia sequence results (wsp gene) revealed a high level of nucleotide diversity (π = 0.00047) under Tajima's D test (P = 0.049). Meanwhile, the same trend of nucleotide diversity (π = 0.00041) was observed in Wolbachia concatenated MLST locus. Furthermore, phylogenetic analysis (wsp and concatenated MLST genes) revealed that all collected samples of CHB attributed to same Wolbachia B-supergroup. Our results strongly suggest that Wolbachia bacteria and mtDNA were highly concordant with each other and Wolbachia can affect the genetic structure and diversity within the CHB populations.}, } @article {pmid29981932, year = {2018}, author = {Qi, X and Kuo, LY and Guo, C and Li, H and Li, Z and Qi, J and Wang, L and Hu, Y and Xiang, J and Zhang, C and Guo, J and Huang, CH and Ma, H}, title = {A well-resolved fern nuclear phylogeny reveals the evolution history of numerous transcription factor families.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {961-977}, doi = {10.1016/j.ympev.2018.06.043}, pmid = {29981932}, issn = {1095-9513}, abstract = {Ferns account for 80% of nonflowering vascular plant species and are the sister lineage of seed plants. Recent molecular phylogenetics have greatly advanced understanding of fern tree of life, but relationships among some major lineages remain unclear. To better resolve the phylogenetic relationships of ferns, we generated transcriptomes from 125 ferns and two lycophytes, with three additional public datasets, to represent all 11 orders and 85% of families of ferns. Our nuclear phylogeny provides strong supports for the monophyly of all four subclasses and nearly all orders and families, and for relationships among these lineages. The only exception is Gleicheniales, which was highly supported as being paraphyletic with Dipteridaceae sister to a clade with Gleicheniaceae + Hymenophyllales. In addition, new and strongly supported phylogenetic relationships are found for suborders and families in Polypodiales. We provide the first dated fern phylogenomic tree using many nuclear genes from a large majority of families, with an estimate for separation of the ancestors of ferns and seed plants in early Devonian at ∼400 Mya and subsequent gradual divergences of fern orders from ∼380 to 200 Mya. Moreover, the newly obtained fern phylogeny provides a framework for gene family analyses, which indicate that the vast majority of transcription factor families found in seed plants were already present in the common ancestor of extant vascular plants. In addition, fern transcription factor genes show similar duplication patterns to those in seed plants, with some showing stable copy number and others displaying independent expansions in both ferns and seed plants. This study provides a robust phylogenetic and gene family evolution framework, as well as rich molecular resources for understanding the morphological and functional evolution in ferns.}, } @article {pmid29981693, year = {2018}, author = {Perez-Garcia, P and Moreno-Risueno, MA}, title = {Stem cells and plant regeneration.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {3-12}, doi = {10.1016/j.ydbio.2018.06.021}, pmid = {29981693}, issn = {1095-564X}, mesh = {Cellular Reprogramming ; Plant Development/*physiology ; Plants ; Regeneration/*physiology ; Stem Cells/metabolism ; }, abstract = {Multicellular organisms show the ability to replace damage cells, tissues and even whole organs through regeneration mechanisms. Plants show a remarkable regenerative potential. While the basic principles of plant regeneration have been known for a number of decades, the molecular and cellular mechanisms underlying such principles are currently starting to emerge. Some of these mechanisms point to the existence of highly reprogrammable cells. Developmental plasticity is a hallmark for stem cells, and stem cells are responsible for the generation of distinctive cell types forming plants. In the last years, a number of players and molecular mechanism regulating stem cell maintenance have been described, and some of them have also been involved in regenerative processes. These discoveries in plant stem cell regulation and regeneration invite us to rethink several of the classical concepts in plant biology such as cell fate specification and even the actual meaning of what we consider stem cells in plants. In this review we will cover some of these discoveries, focusing on the role of the plant stem cell function and regulation during cell and organ regeneration.}, } @article {pmid29981692, year = {2018}, author = {Hutchins, EJ and Kunttas, E and Piacentino, ML and Howard, AGA and Bronner, ME and Uribe, RA}, title = {Migration and diversification of the vagal neural crest.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.07.004}, pmid = {29981692}, issn = {1095-564X}, support = {R01 DE024157/DE/NIDCR NIH HHS/United States ; P01 HD037105/HD/NICHD NIH HHS/United States ; F32 DE026355/DE/NIDCR NIH HHS/United States ; F32 HD088022/HD/NICHD NIH HHS/United States ; L40 HD096443/HD/NICHD NIH HHS/United States ; L40 DE028128/DE/NIDCR NIH HHS/United States ; F32 HD087026/HD/NICHD NIH HHS/United States ; }, abstract = {Arising within the neural tube between the cranial and trunk regions of the body axis, the vagal neural crest shares interesting similarities in its migratory routes and derivatives with other neural crest populations. However, the vagal neural crest is also unique in its ability to contribute to diverse organs including the heart and enteric nervous system. This review highlights the migratory routes of the vagal neural crest and compares them across multiple vertebrates. We also summarize recent advances in understanding vagal neural crest ontogeny and discuss the contribution of this important neural crest population to the cardiovascular system and endoderm-derived organs, including the thymus, lungs and pancreas.}, } @article {pmid29981583, year = {2018}, author = {Nyangahu, DD and Lennard, KS and Brown, BP and Darby, MG and Wendoh, JM and Havyarimana, E and Smith, P and Butcher, J and Stintzi, A and Mulder, N and Horsnell, W and Jaspan, HB}, title = {Disruption of maternal gut microbiota during gestation alters offspring microbiota and immunity.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {124}, pmid = {29981583}, issn = {2049-2618}, support = {GPH-129340//CIHR/Canada ; MOP-114872//CIHR/Canada ; ECD-144627//CIHR/Canada ; }, mesh = {Adaptive Immunity/*immunology ; Animals ; Animals, Newborn/*immunology/microbiology ; Anti-Bacterial Agents/pharmacology ; Antibodies, Bacterial/*immunology ; B-Lymphocytes/*immunology ; *Breast Feeding ; CD4-Positive T-Lymphocytes/*immunology ; Female ; Gastrointestinal Microbiome/genetics/*immunology ; Immunoglobulin G/immunology ; Immunoglobulin M/immunology ; Intestines/microbiology ; Lymphocyte Count ; Mice ; Mice, Inbred BALB C ; Pregnancy ; Vancomycin/pharmacology ; }, abstract = {BACKGROUND: Early life microbiota is an important determinant of immune and metabolic development and may have lasting consequences. The maternal gut microbiota during pregnancy or breastfeeding is important for defining infant gut microbiota. We hypothesized that maternal gut microbiota during pregnancy and breastfeeding is a critical determinant of infant immunity. To test this, pregnant BALB/c dams were fed vancomycin for 5 days prior to delivery (gestation; Mg), 14 days postpartum during nursing (Mn), or during gestation and nursing (Mgn), or no vancomycin (Mc). We analyzed adaptive immunity and gut microbiota in dams and pups at various times after delivery.

RESULTS: In addition to direct alterations to maternal gut microbial composition, pup gut microbiota displayed lower α-diversity and distinct community clusters according to timing of maternal vancomycin. Vancomycin was undetectable in maternal and offspring sera, therefore the observed changes in the microbiota of stomach contents (as a proxy for breastmilk) and pup gut signify an indirect mechanism through which maternal intestinal microbiota influences extra-intestinal and neonatal commensal colonization. These effects on microbiota influenced both maternal and offspring immunity. Maternal immunity was altered, as demonstrated by significantly higher levels of both total IgG and IgM in Mgn and Mn breastmilk when compared to Mc. In pups, lymphocyte numbers in the spleens of Pg and Pn were significantly increased compared to Pc. This increase in cellularity was in part attributable to elevated numbers of both CD4+ T cells and B cells, most notable Follicular B cells.

CONCLUSION: Our results indicate that perturbations to maternal gut microbiota dictate neonatal adaptive immunity.}, } @article {pmid29981578, year = {2018}, author = {Bengtsson-Palme, J}, title = {The diversity of uncharacterized antibiotic resistance genes can be predicted from known gene variants-but not always.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {125}, pmid = {29981578}, issn = {2049-2618}, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/*drug effects/*genetics ; Databases, Genetic ; Drug Resistance, Multiple, Bacterial/*genetics ; Genes, Bacterial/genetics ; Genetic Variation/genetics ; Humans ; Metagenome/*genetics ; Polymerase Chain Reaction ; }, abstract = {BACKGROUND: Antibiotic resistance is considered one of the most urgent threats to modern healthcare, and the role of the environment in resistance development is increasingly recognized. It is often assumed that the abundance and diversity of known resistance genes are representative also for the non-characterized fraction of the resistome in a given environment, but this assumption has not been verified. In this study, this hypothesis is tested, using the resistance gene profiles of 1109 metagenomes from various environments.

RESULTS: This study shows that the diversity and abundance of known antibiotic resistance genes can generally predict the diversity and abundance of undescribed resistance genes. However, the extent of this predictability is dependent on the type of environment investigated. Furthermore, it is shown that carefully selected small sets of resistance genes can describe total resistance gene diversity remarkably well.

CONCLUSIONS: The results of this study suggest that knowledge gained from large-scale quantifications of known resistance genes can be utilized as a proxy for unknown resistance factors. This is important for current and proposed monitoring efforts for environmental antibiotic resistance and has implications for the design of risk ranking strategies and the choices of measures and methods for describing resistance gene abundance and diversity in the environment.}, } @article {pmid29981470, year = {2018}, author = {Ye, WQ and Yap, ZY and Li, P and Comes, HP and Qiu, YX}, title = {Plastome organization, genome-based phylogeny and evolution of plastid genes in Podophylloideae (Berberidaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {978-987}, doi = {10.1016/j.ympev.2018.07.001}, pmid = {29981470}, issn = {1095-9513}, abstract = {Species of Podophylloideae (Berberidaceae, Ranunculales) are of great pharmacogenetic importance and represent the classic biogeographic disjunction between eastern Asia (EA; 10 ssp.) and eastern North America (ENA; 2 ssp.). However, previous molecular studies of this group suffered from low phylogenetic resolution and/or insufficient marker variability. This study is the first to report whole-plastome sequence data for all 12 species of Podophylloideae (14 individuals) and a close relative, Achlys triphylla. These 15 plastomes proved highly similar in overall size (156,240-157,370 bp), structure, gene order and content, also when compared to other Ranunculales, but also revealed some structural variations caused by the expansion or contraction of the inverted repeats (IRs) into or out of adjacent single-copy regions. Our phylogenomic analysis, based on 63 plastome-derived protein-coding genes (CDS), supported the monophyly of Podophylloideae and its two major genera (EA: Dysosma, EA/ENA: Diphylleia), with Podophyllum peltatum L. (ENA) being more closely related to Diphylleia than to the group's earliest diverging species, Sinopodophyllum hexandrum (EA). Furthermore, within this subfamily/dataset, matK was identified as the fastest evolving gene, which proved to be under positive selection especially in more recently derived, lower-elevation lineages of Dysosma, possibly reflecting an adaptive response to novel environmental (i.e. subtropical compared to higher-elevation/alpine) conditions. Finally, several highly variable noncoding regions were identified in the plastomes of Podophylloideae and Ranunculales. These highly variable loci should be the best choices for future phylogenetic, phylogeographic, and population-level genetic studies. Overall, our results demonstrate the power of plastid phylogenomics to improve phylogenetic resolution, and contribute to a better understanding of plastid gene evolution in Podophylloideae.}, } @article {pmid29981311, year = {2018}, author = {Grover, S and Williams, ME and Kaiser, R and Hughes, JT and Gresham, L and Rebeiz, M and Williams, TM}, title = {Augmentation of a wound response element accompanies the origin of a Hox-regulated Drosophila abdominal pigmentation trait.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {159-175}, pmid = {29981311}, issn = {1095-564X}, support = {P40 OD018537/OD/NIH HHS/United States ; R01 GM084947/GM/NIGMS NIH HHS/United States ; R01 GM114093/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; GATA Transcription Factors/genetics/*metabolism ; Pigmentation/*physiology ; *Quantitative Trait, Heritable ; Response Elements/*physiology ; }, abstract = {A challenge for evolutionary research is to uncover how new morphological traits evolve the coordinated spatial and temporal expression patterns of genes that govern their formation during development. Detailed studies are often limited to characterizing how one or a few genes contributed to a trait's emergence, and thus our knowledge of how entire GRNs evolve their coordinated expression of each gene remains unresolved. The melanic color patterns decorating the male abdominal tergites of Drosophila (D.) melanogaster evolved in part by novel expression patterns for genes acting at the terminus of a pigment metabolic pathway, driven by cis-regulatory elements (CREs) with distinct mechanisms of Hox regulation. Here, we examined the expression and evolutionary histories of two important enzymes in this pathway, encoded by the pale and Ddc genes. We found that while both genes exhibit dynamic patterns of expression, a robust pattern of Ddc expression specifically evolved in the lineage of fruit flies with pronounced melanic abdomens. Derived Ddc expression requires the activity of a CRE previously shown to activate expression in response to epidermal wounding. We show that a binding site for the Grainy head transcription factor that promotes the ancestral wound healing function of this CRE is also required for abdominal activity. Together with previous findings in this system, our work shows how the GRN for a novel trait emerged by assembling unique yet similarly functioning CREs from heterogeneous starting points.}, } @article {pmid29981310, year = {2018}, author = {Li, J and Yuan, Y and He, J and Feng, J and Han, X and Jing, J and Ho, TV and Xu, J and Chai, Y}, title = {Constitutive activation of hedgehog signaling adversely affects epithelial cell fate during palatal fusion.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {191-203}, pmid = {29981310}, issn = {1095-564X}, support = {R37 DE012711/DE/NIDCR NIH HHS/United States ; R90 DE022528/DE/NIDCR NIH HHS/United States ; U01 DE024421/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Cell Adhesion/physiology ; Embryo, Mammalian/cytology/*metabolism ; Epithelial Cells/cytology/*metabolism ; Hedgehog Proteins/genetics/*metabolism ; Interferon Regulatory Factors/genetics/metabolism ; Mice ; Mice, Transgenic ; Palate/cytology/*embryology ; Phosphoproteins/genetics/metabolism ; Signal Transduction/*physiology ; Trans-Activators/genetics/metabolism ; }, abstract = {Cleft palate is one of the most common craniofacial congenital defects in humans. It is associated with multiple genetic and environmental risk factors, including mutations in the genes encoding signaling molecules in the sonic hedgehog (Shh) pathway, which are risk factors for cleft palate in both humans and mice. However, the function of Shh signaling in the palatal epithelium during palatal fusion remains largely unknown. Although components of the Shh pathway are localized in the palatal epithelium, specific inhibition of Shh signaling in palatal epithelium does not affect palatogenesis. We therefore utilized a hedgehog (Hh) signaling gain-of-function mouse model, K14-Cre;R26SmoM2, to uncover the role of Shh signaling in the palatal epithelium during palatal fusion. In this study, we discovered that constitutive activation of Hh signaling in the palatal epithelium results in submucous cleft palate and persistence of the medial edge epithelium (MEE). Further investigation revealed that precise downregulation of Shh signaling is required at a specific time point in the MEE during palatal fusion. Upregulation of Hh signaling in the palatal epithelium maintains the proliferation of MEE cells. This may be due to a dysfunctional p63/Irf6 regulatory loop. The resistance of MEE cells to apoptosis is likely conferred by enhancement of a cell adhesion network through the maintenance of p63 expression. Collectively, our data illustrate that persistent Hh signaling in the palatal epithelium contributes to the etiology and pathogenesis of submucous cleft palate through its interaction with a p63/Irf6-dependent biological regulatory loop and through a p63-induced cell adhesion network.}, } @article {pmid29981309, year = {2018}, author = {Yuan, T and York, JR and McCauley, DW}, title = {Gliogenesis in lampreys shares gene regulatory interactions with oligodendrocyte development in jawed vertebrates.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {176-190}, doi = {10.1016/j.ydbio.2018.07.002}, pmid = {29981309}, issn = {1095-564X}, mesh = {Animals ; Embryo, Nonmammalian/cytology/*embryology ; *Fish Proteins/biosynthesis/genetics ; Gene Expression Regulation, Developmental/*physiology ; *Lampreys/embryology/genetics ; Neural Tube/cytology/*embryology ; Neuroglia/cytology/*metabolism ; Oligodendroglia/cytology/*metabolism ; }, abstract = {Glial cells in the nervous system regulate and support many functions related to neuronal activity. Understanding how the vertebrate nervous system has evolved demands a greater understanding of the mechanisms controlling evolution and development of glial cells in basal vertebrates. Among vertebrate glia, oligodendrocytes form an insulating myelin layer surrounding axons of the central nervous system (CNS) in jawed vertebrates. Jawless vertebrates lack myelinated axons but it is unclear when oligodendrocytes or the regulatory mechanisms controlling their development evolved. To begin to investigate the evolution of mechanisms controlling glial development, we identified key genes required for the differentiation of oligodendrocytes in gnathostomes, including Nkx2.2, SoxE genes, and PDGFR, analyzed their expression, and used CRISPR/Cas9 genome editing to perturb their functions in a primitively jawless vertebrate, the sea lamprey. We show in lamprey that orthologs required for oligodendrocyte development in jawed vertebrates are expressed in the lamprey ventral neural tube, in similar locations where gnathostome oligodendrocyte precursor cells (OPC) originate. In addition, they appear to be under the control of conserved mechanisms that regulate OPC development in jawed vertebrates and may also function in gliogenesis. Our results suggest that although oligodendrocytes first emerged in jawed vertebrates, regulatory mechanisms required for their development predate the divergence of jawless and jawed vertebrates.}, } @article {pmid29980814, year = {2018}, author = {Molina, R and Rivera, D and Mora, V and López, G and Rosas, S and Spaepen, S and Vanderleyden, J and Cassán, F}, title = {Regulation of IAA Biosynthesis in Azospirillum brasilense Under Environmental Stress Conditions.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1408-1418}, pmid = {29980814}, issn = {1432-0991}, mesh = {Azospirillum brasilense/*genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Culture Media/chemistry/metabolism ; *Gene Expression Regulation, Bacterial ; Indoleacetic Acids/*metabolism ; Plant Growth Regulators/*biosynthesis ; Tryptophan/metabolism ; }, abstract = {Indole-3-acetic acid (IAA) is one of the most important molecules produced by Azospirillum sp., given that it affects plant growth and development. Azospirillum brasilense strains Sp245 and Az39 (pFAJ64) were pre-incubated in MMAB medium plus 100 mg/mL L-tryptophan and treated with or exposed to the following (a) abiotic and (b) biotic stress effectors: (a) 100 mM NaCl or Na2SO4, 4.0% (w/v) PEG6000, 0.5 mM H2O2, 0.1 mM abscisic acid, 0.1 mM 1-aminocyclopropane 1-carboxylic acid, 45 °C or daylight, and (b) 4.0% (v/v) filtered supernatant of Pseudomonas savastanoi (Ps) or Fusarium oxysporum (Fo), 0.1 mM salicylic acid (SA), 0.1 mM methyl jasmonic acid (MeJA), and 0.01% (w/v) chitosan (CH). After 30 and 120 min of incubation, biomass production, cell viability, IAA concentration (µg/mL), and ipdC gene expression were measured. Our results show that IAA production increases with daylight or in the presence of PEG6000, ABA, SA, CH, and Fo. On the contrary, exposure to 45 °C or treatment with H2O2, NaCl, Na2SO4, ACC, MeJA, and Ps decrease IAA biosynthesis. In this report, growth and IAA biosynthesis in A. brasilense under biotic and abiotic stress conditions are discussed from the point of view of their role in bacterial lifestyle and their potential application as bioproducts.}, } @article {pmid29980813, year = {2018}, author = {Siddiqi, MZ and Liu, Q and Choi, KD and Lee, SY and Lee, JH and Im, WT}, title = {Actinomadura hankyongense sp. nov. Isolated From Soil of Ginseng Cultivating Field.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1401-1407}, pmid = {29980813}, issn = {1432-0991}, support = {2014M3A6A8066437//This research was supported by the project on survey and excavation of Korean indigenous species of the National Institute of Biological Resources (NIBR) under the Ministry of Environment and by the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Education, Science and Technology (2014M3A6A8066437)./ ; }, mesh = {Actinomycetales/classification/genetics/*isolation & purification/metabolism ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry/metabolism ; Genotype ; Panax/*growth & development/microbiology ; Phylogeny ; *Soil Microbiology ; }, abstract = {A Gram-positive, rod-shaped, non-spore-forming, and aerobic bacterium (Gsoil 556T) was isolated from soil of a ginseng field and subjected to its taxonomic position. Based on 16S rRNA gene sequence similarity, strain Gsoil 556T was shown to belong to the genus Actinomadura of the family Thermomonosporaceae and was closely related to A. montaniterrae CYP1-1BT (99.3%), A. nitritigenes DSM 44137T (98.7%), and A. rudentiformis HMC1T (98.5%), while it showed less than 98.4% sequence similarity to the other species of this genus. Phylogenetic analysis based on the 16S rRNA gene sequence indicated that it is most closely related to A. rudentiformis HMC1T and A. nitritigenes DSM 44137T. The DNA G+C content was 73.1 mol%. The peptidoglycan was meso-diaminopimelic acid and the whole-cell sugar contained fucose, galactose, glucose, mannose, and ribose. The predominant menaquinone (KK) was MK-9(H8) [55%] and MK-9(H6) [45%]. The major cellular fatty acids were C14:0, C16:0, C18:1 ω9c and summed feature 3 (C16:1 ω6c/C16:1 ω7c). All these data supported the affiliation of strain Gsoil 556T to the genus Actinomadura. The DNA-DNA hybridization between strain Gsoil 556T and its phylogenetically closest relatives were less than 40%. Furthermore, the results of physiological and biochemical tests enabled strain Gsoil 556T to be differentiated genotypically and phenotypically from currently known Actinomadura species. Therefore, strain Gsoil 556T represents a novel species of the genus Actinomadura, for which the name Actinomadura hankyongense sp. nov. is proposed. The type strain Gsoil 556T (=KACC 19438T=LMG 30327T).}, } @article {pmid29980812, year = {2018}, author = {Rech, MM and Swalla, BM and Dobranic, JK}, title = {Evaluation of Legiolert for Quantification of Legionella pneumophila from Non-potable Water.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1282-1289}, pmid = {29980812}, issn = {1432-0991}, mesh = {Bacteriological Techniques/*methods ; Centers for Disease Control and Prevention (U.S.) ; Fresh Water/*microbiology ; Humans ; Legionella pneumophila/classification/genetics/*isolation & purification ; Legionnaires' Disease/microbiology ; Sensitivity and Specificity ; United States ; Water Supply ; }, abstract = {Legiolert® is a new culture method for quantification of Legionella pneumophila, which is the primary species associated with Legionnaires' disease. The test is based on a most probable number approach, and differs significantly from traditional culture methods by providing results at 7 days, rapid sample preparation and analysis, and objective interpretation of test results. In this study, we compared the performance of Legiolert with the U.S. Centers for Disease Control and Prevention (CDC) method for detection of L. pneumophila from non-potable samples, primarily comprising cooling tower waters. Our results demonstrated no significant difference between Legiolert and the CDC method for quantification of L. pneumophila. However, Legiolert showed a significant increase in sensitivity when water samples containing higher L. pneumophila concentrations were examined. Cooling tower waters often contain non-Legionella organisms (NLO) that interfere with traditional Legionella test methods, and we observed varying degrees of NLO interference on many CDC method plates. In contrast, Legiolert was resistant to NLO interference and produced a very low rate of false-positive results. Collectively, Legiolert is a sensitive and specific method for quantification of L. pneumophila from non-potable water that provides advantages over the CDC method.}, } @article {pmid29980769, year = {2018}, author = {Gizzi, AS and Grove, TL and Arnold, JJ and Jose, J and Jangra, RK and Garforth, SJ and Du, Q and Cahill, SM and Dulyaninova, NG and Love, JD and Chandran, K and Bresnick, AR and Cameron, CE and Almo, SC}, title = {Publisher Correction: A naturally occurring antiviral ribonucleotide encoded by the human genome.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {E3}, doi = {10.1038/s41586-018-0355-0}, pmid = {29980769}, issn = {1476-4687}, abstract = {Change history: In the HTML version of this Letter, Extended Data Fig. 4 incorrectly corresponded to Fig. 4 (the PDF version of the figure was correct). This has been corrected online.}, } @article {pmid29980736, year = {2018}, author = {Mehta, D}, title = {Lab heads should learn to talk about racism.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {153}, doi = {10.1038/d41586-018-05646-4}, pmid = {29980736}, issn = {1476-4687}, mesh = {*Communication ; Education, Graduate ; Humans ; Laboratories ; Mentors/*psychology ; Racism/*prevention & control ; Research Personnel/ethics/*psychology ; }, } @article {pmid29980735, year = {2018}, author = {Muller, M}, title = {Cape Town's drought: don't blame climate change.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {174-176}, doi = {10.1038/d41586-018-05649-1}, pmid = {29980735}, issn = {1476-4687}, mesh = {Australia ; Brazil ; Climate Change ; Conservation of Water Resources/economics/methods/trends ; *Droughts ; Humans ; *Politics ; South Africa ; Spain ; *Water Supply/economics/methods ; }, } @article {pmid29980649, year = {2018}, author = {Doi, T and Abdolrahmani, M and Fujita, I}, title = {Spatial pooling inherent to intrinsic signal optical imaging might cause V2 to resemble a solution to the stereo correspondence problem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E6967-E6968}, pmid = {29980649}, issn = {1091-6490}, mesh = {*Depth Perception ; *Photic Stimulation ; }, } @article {pmid29980648, year = {2018}, author = {Yin, H and Fu, P and Lu, HD and Tanigawa, H and Roe, AW and Chen, G}, title = {Reply to Doi et al.: Functional architecture matters in the formation of perception.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E6969-E6971}, pmid = {29980648}, issn = {1091-6490}, mesh = {*Perception ; }, } @article {pmid29980647, year = {2018}, author = {Ballesteros, A and Swartz, KJ}, title = {Lipids surf the groove in scramblases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7648-7650}, pmid = {29980647}, issn = {1091-6490}, mesh = {*Cell Membrane ; *Lipids ; }, } @article {pmid29980646, year = {2018}, author = {Levy, I}, title = {Information utility in the human brain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7846-7848}, pmid = {29980646}, issn = {1091-6490}, mesh = {*Brain ; Humans ; }, } @article {pmid29980232, year = {2018}, author = {Hani, J and Abdel Nour, G and Matta, J and Jazzar, B and Pfaffl, MW and Hanna-Wakim, L and Abdel Nour, AM}, title = {Shisha microbiota: the good, the bad and the not so ugly.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {446}, pmid = {29980232}, issn = {1756-0500}, mesh = {Adult ; Bacteria/genetics/*isolation & purification ; Equipment Contamination ; *Gastrointestinal Microbiome ; Humans ; RNA, Ribosomal, 16S ; Smoking ; Smoking Water Pipes/*microbiology ; Tobacco ; }, abstract = {OBJECTIVE: Over the last decade, there has been a rapid expansion of the trendy water pipe smoking around the world especially among younger adults. The initial objective of this study was to identify the microbiota of the shisha, which may either be of no harm for the smoker or enhance the threat on his well-being. The total DNA for the metagenomics study was conducted on three different shishas from three different delivery shops in Jounieh, Lebanon. The microbiota in two solid parts of the shisha, shaft and hose, were analysed including the fresh tobacco and the water in the bowl. All samples were analysed using high-throughput sequencing of 16S rRNA gene amplicons.

RESULTS: Overall, more than 40 bacterial genera were found in the three investigated shishas, some are commensal others are pathogenic. All three shishas showed similar microbial content regarding the bacteria inhabiting in water, shaft, or hose. From the results of this study it appears that a very large quantity of bacteria was found in the water pipes, some are harmful and others beneficial. We assume that the presence of gut dependent microbiota is related to the loose hygienic conditions in which the shisha is prepared.}, } @article {pmid29980191, year = {2018}, author = {St John, JC and Tsai, TS}, title = {The association of mitochondrial DNA haplotypes and phenotypic traits in pigs.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {41}, pmid = {29980191}, issn = {1471-2156}, support = {2012/1024//Australian Pork Limited/ ; }, abstract = {BACKGROUND: The mitochondrial genome (mtDNA) is an emerging determiner of phenotypic traits and disease. mtDNA is inherited in a strict maternal fashion from the population of mitochondria present in the egg at fertilisation. Individuals are assigned to mtDNA haplotypes and those with sequences that cluster closely have common origins and their migration patterns can be mapped. Previously, we identified five mtDNA haplotypes in the commercial breeding lines of Australian pigs, which defined their common origins, and showed how these mtDNA haplotypes influenced litter size and reproductive function in terms of egg and embryo quality and fertilisation efficiency.

RESULTS: We have determined whether mtDNA haplotypes influence other phenotypic traits. These include fat density; muscle depth; fat to leanness ratios; lifetime daily gain; teat quality; muscle score; front and rear leg assessments; percentage offspring weaned; weaning to oestrus intervals; gilt age at selection; and gestational length. In all, we assessed 5687 pigs of which 2762 were females and 2925 were males. We assessed all animals together and then by gender. We further assessed by gender based on whether a sire had joined with females from only one haplotype or from more than one haplotype. We determined that fat density, muscle depth, fat to leanness ratios, lifetime daily gain and teat quality were influenced by mtDNA haplotype and that there were gender specific effects on teat quality.

CONCLUSIONS: Our data illustrate that mtDNA haplotypes are associated with a number of important phenotypic traits indicative of economic breeding values in breeding pigs with gender-specific differences. Interestingly, there are 'trade offs' whereby some mtDNA haplotypes perform better for one selection criterion, such as muscle depth, but less so for another, for example teat quality, indicating that pig mtDNA haplotypes are afforded an advantage in one respect but a disadvantage in another.}, } @article {pmid29980168, year = {2018}, author = {Rhee, YH and Moon, JH and Mo, JH and Pham, T and Chung, PS}, title = {mTOR and ROS regulation by anethole on adipogenic differentiation in human mesenchymal stem cells.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {12}, pmid = {29980168}, issn = {1471-2121}, support = {2017R1D1A1B03030060//National Research Foundation of Korea/International ; HI15C1524//Ministry of health & Welfare, Republic of Korea/International ; 2012K1A4A3053142//the Ministry of Science and ICT/International ; }, mesh = {Adipogenesis/*drug effects ; Anisoles/chemistry/*pharmacology ; Apoptosis/drug effects ; Biomarkers/metabolism ; Cell Proliferation/drug effects ; Humans ; Mesenchymal Stem Cells/*cytology/drug effects/*metabolism ; Reactive Oxygen Species/*metabolism ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {BACKGROUND: Adipocyte differentiation of human mesenchymal stem cells (hMSCs) is dependent on mitochondrial metabolism and reactive oxygen species (ROS) to initiate adipocyte differentiation. Although anethole has been known as an anti-oxidant and lipid peroxidation inhibitor, there is little investigated about its role in adipogenic differentiation.

METHODS: The effects on cytotoxicity and proliferation of anethole in hMSCs were measured by the MTT assay. The anti-adipogenic effect of anethole on hMSCs was analyzed by Oil Red O staining and western blot analysis. The anti-oxidant activity of anethole on hMSC was assessed by flowcytometry and fluorescence staining using 2',7' -dichlorofluorescin diacetate (DCFDA). The western blotting was used to detect of phospho-Akt, phospho-mTOR, phospho-p70S6K, PPARγ, and phsopho-AMP-activated kinase (AMPK).

RESULTS: Anethole suppressed the adipogenic differentiation of hMSCs through down-regulation of Akt-mTOR-p70S6K-PPARγ and up-regulation of AMPK. Anethole affected oxidative conditions through ROS generation. Anethole also rescued AMPK activity and reduced activation of mTOR-p70S6K-PPARγ under oxidative conditions in presence of exogenous hydrogen peroxide.

CONCLUSION: ROS and mTOR regulation is a crucial factor in adipogenic differentiation, anethole has an important role in regulating activities of mTOR/PPARγ and ROS control in adipogenic differentiation of hMSCs.}, } @article {pmid29978525, year = {2018}, author = {Arbuthnott, D and Whitlock, MC}, title = {Environmental stress does not increase the mean strength of selection.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1599-1606}, doi = {10.1111/jeb.13351}, pmid = {29978525}, issn = {1420-9101}, support = {//NSERC PDF/ ; }, abstract = {A common intuition among evolutionary biologists and ecologists is that environmental stress will increase the strength of selection against deleterious alleles and among alternate genotypes. However, the strength of selection is determined by the relative fitness differences among genotypes, and there is no theoretical reason why these differences should be exaggerated as mean fitness decreases. We update a recent review of the empirical results pertaining to environmental stress and the strength of selection and find that there is no overall trend towards increased selection under stress, in agreement with other recent analyses of existing data. The majority of past studies measure the strength of selection by quantifying the decrease in fitness imposed by single or multiple mutations in different environments. However, selection rarely acts on one locus independently, and the strength of selection will be determined by variation across the whole genome. We used 20 inbred lines of Drosophila melanogaster to make repeated fitness measurements of the same genotypes in four different environments. This framework allowed us to determine the variation in fitness attributable to genotype across stressful environments and to calculate the opportunity for selection among these genotypes in each stress. Although we found significant decreases in mean fitness in our stressful environments, we did not find any significant differences in the strength of selection among any of the four measured environments. Therefore, in agreement with our updated review, we find no evidence for the oft-cited verbal model that stress increases the strength of selection.}, } @article {pmid29978521, year = {2018}, author = {Merilaita, S and Kelley, JL}, title = {Scary clowns: adaptive function of anemonefish coloration.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1558-1571}, doi = {10.1111/jeb.13350}, pmid = {29978521}, issn = {1420-9101}, support = {//Ella and Georg Ehrnrooth Foundation/ ; //School of Biological Sciences at The University of Western Australia/ ; }, abstract = {Clownfishes, with their showy coloration, are well known for their symbiosis with sea anemones and for their hierarchical reproductive system, but the function of their coloration is unclear. We used a phylogeny of 27 clownfish species to test whether fish coloration (i) serves a protective function that involves their anemone hosts, or (ii) signals species identity in species with overlapping host ranges that can potentially share the same host. We tested for an association between fish colour pattern traits, host morphology and host toxicity and examined coloration in relation to host sharing and geographic proximity. Fish with fewer stripes occupied fewer anemone species, and hosts with shorter tentacles, than fish with multiple stripes. There was a negative relationship between anemone toxicity and tentacle length and these protective traits together were correlated with the evolution of stripes. Host sharing or range overlap was not associated with coloration divergence. We propose that ancestral anemonefishes had multiple stripes that served for hiding/camouflage among the hosts' long tentacles, whereas increased specialization towards fewer and more toxic hosts (with shorter tentacles) led to the use of coloration as an aposematic signal. The intriguing notion that an aposematic signal could advertise the defence of another species may reflect the unique symbiotic relationship between anemonefishes and their hosts.}, } @article {pmid29977111, year = {2018}, author = {Qi, ZH and Li, KC and Ma, JL and Yao, YH and Liu, LY}, title = {Novel Method of 3-Dimensional Graphical Representation for Proteins and Its Application.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318777755}, pmid = {29977111}, issn = {1176-9343}, abstract = {In this article, we propose a 3-dimensional graphical representation of protein sequences based on 10 physicochemical properties of 20 amino acids and the BLOSUM62 matrix. It contains evolutionary information and provides intuitive visualization. To further analyze the similarity of proteins, we extract a specific vector from the graphical representation curve. The vector is used to calculate the similarity distance between 2 protein sequences. To prove the effectiveness of our approach, we apply it to 3 real data sets. The results are consistent with the known evolution fact and show that our method is effective in phylogenetic analysis.}, } @article {pmid29977062, year = {2018}, author = {Szenker-Ravi, E and Altunoglu, U and Leushacke, M and Bosso-Lefèvre, C and Khatoo, M and Thi Tran, H and Naert, T and Noelanders, R and Hajamohideen, A and Beneteau, C and de Sousa, SB and Karaman, B and Latypova, X and Başaran, S and Yücel, EB and Tan, TT and Vlaminck, L and Nayak, SS and Shukla, A and Girisha, KM and Le Caignec, C and Soshnikova, N and Uyguner, ZO and Vleminckx, K and Barker, N and Kayserili, H and Reversade, B}, title = {Author Correction: RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {E7}, doi = {10.1038/s41586-018-0296-7}, pmid = {29977062}, issn = {1476-4687}, abstract = {In this Letter, the surname of author Lena Vlaminck was misspelled 'Vlaeminck'. In addition, author Kris Vleminckx should have been associated with affiliation 16 (Center for Medical Genetics, Ghent University, Ghent, Belgium). These have been corrected online.}, } @article {pmid29977061, year = {2018}, author = {Shoshkes-Carmel, M and Wang, YJ and Wangensteen, KJ and Tóth, B and Kondo, A and Massasa, EE and Itzkovitz, S and Kaestner, KH}, title = {Author Correction: Subepithelial telocytes are an important source of Wnts that supports intestinal crypts.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {E29}, doi = {10.1038/s41586-018-0286-9}, pmid = {29977061}, issn = {1476-4687}, abstract = {Change history: In this Letter, the surname of author Efi E. Massasa was misspelled 'Massassa'. This error has been corrected online.}, } @article {pmid29976950, year = {2018}, author = {Hofer, U}, title = {Candida tolerates and persists.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {520-521}, doi = {10.1038/s41579-018-0056-6}, pmid = {29976950}, issn = {1740-1534}, } @article {pmid29976841, year = {2018}, author = {Vasudevan, S and Flashner-Abramson, E and Remacle, F and Levine, RD and Kravchenko-Balasha, N}, title = {Personalized disease signatures through information-theoretic compaction of big cancer data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7694-7699}, pmid = {29976841}, issn = {1091-6490}, mesh = {*Databases, Genetic ; *Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Humans ; *Neoplasms/classification/genetics/metabolism ; *Patient-Specific Modeling ; *Transcriptome ; }, abstract = {Every individual cancer develops and grows in its own specific way, giving rise to a recognized need for the development of personalized cancer diagnostics. This suggested that the identification of patient-specific oncogene markers would be an effective diagnostics approach. However, tumors that are classified as similar according to the expression levels of certain oncogenes can eventually demonstrate divergent responses to treatment. This implies that the information gained from the identification of tumor-specific biomarkers is still not sufficient. We present a method to quantitatively transform heterogeneous big cancer data to patient-specific transcription networks. These networks characterize the unbalanced molecular processes that deviate the tissue from the normal state. We study a number of datasets spanning five different cancer types, aiming to capture the extensive interpatient heterogeneity that exists within a specific cancer type as well as between cancers of different origins. We show that a relatively small number of altered molecular processes suffices to accurately characterize over 500 tumors, showing extreme compaction of the data. Every patient is characterized by a small specific subset of unbalanced processes. We validate the result by verifying that the processes identified characterize other cancer patients as well. We show that different patients may display similar oncogene expression levels, albeit carrying biologically distinct tumors that harbor different sets of unbalanced molecular processes. Thus, tumors may be inaccurately classified and addressed as similar. These findings highlight the need to expand the notion of tumor-specific oncogenic biomarkers to patient-specific, comprehensive transcriptional networks for improved patient-tailored diagnostics.}, } @article {pmid29976840, year = {2018}, author = {Liu, BH and Jobichen, C and Chia, CSB and Chan, THM and Tang, JP and Chung, TXY and Li, J and Poulsen, A and Hung, AW and Koh-Stenta, X and Tan, YS and Verma, CS and Tan, HK and Wu, CS and Li, F and Hill, J and Joy, J and Yang, H and Chai, L and Sivaraman, J and Tenen, DG}, title = {Targeting cancer addiction for SALL4 by shifting its transcriptome with a pharmacologic peptide.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7119-E7128}, pmid = {29976840}, issn = {1091-6490}, support = {P01 CA066996/CA/NCI NIH HHS/United States ; P01 HL095489/HL/NHLBI NIH HHS/United States ; }, mesh = {*Antineoplastic Agents/chemistry/pharmacology ; Cell Line, Tumor ; Gene Expression Regulation/*drug effects ; Humans ; *Neoplasm Proteins/chemistry/genetics/metabolism ; *Neoplasms/chemistry/drug therapy/genetics/metabolism ; *Peptides/chemistry/pharmacology ; Protein Structure, Quaternary ; Retinoblastoma-Binding Protein 4/chemistry/genetics/metabolism ; *Transcription Factors/chemistry/genetics/metabolism ; Transcriptome/*drug effects ; }, abstract = {Sal-like 4 (SALL4) is a nuclear factor central to the maintenance of stem cell pluripotency and is a key component in hepatocellular carcinoma, a malignancy with no effective treatment. In cancer cells, SALL4 associates with nucleosome remodeling deacetylase (NuRD) to silence tumor-suppressor genes, such as PTEN. Here, we determined the crystal structure of an amino-terminal peptide of SALL4(1-12) complexed to RBBp4, the chaperone subunit of NuRD, at 2.7 Å, and subsequent design of a potent therapeutic SALL4 peptide (FFW) capable of antagonizing the SALL4-NURD interaction using systematic truncation and amino acid substitution studies. FFW peptide disruption of the SALL4-NuRD complex resulted in unidirectional up-regulation of transcripts, turning SALL4 from a dual transcription repressor-activator mode to singular transcription activator mode. We demonstrate that FFW has a target affinity of 23 nM, and displays significant antitumor effects, inhibiting tumor growth by 85% in xenograft mouse models. Using transcriptome and survival analysis, we discovered that the peptide inhibits the transcription-repressor function of SALL4 and causes massive up-regulation of transcripts that are beneficial to patient survival. This study supports the SALL4-NuRD complex as a drug target and FFW as a viable drug candidate, showcasing an effective strategy to accurately target oncogenes previously considered undruggable.}, } @article {pmid29976839, year = {2018}, author = {Olson, AL}, title = {RalA signaling may reveal the true nature of 3T3-L1 adipocytes as a model for thermogenic adipocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7651-7653}, pmid = {29976839}, issn = {1091-6490}, mesh = {*3T3-L1 Cells ; *Adipocytes ; Animals ; Insulin ; Signal Transduction ; }, } @article {pmid29976838, year = {2018}, author = {Sinclair, KD}, title = {When maternal periconceptional diet affects neurological development, it's time to think.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {7852-7854}, pmid = {29976838}, issn = {1091-6490}, support = {BB/K017810/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/R007985/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Diet ; *Thinking ; }, } @article {pmid29976828, year = {2018}, author = {Perrigo, A}, title = {The road less traveled.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {102}, doi = {10.1126/science.361.6397.102}, pmid = {29976828}, issn = {1095-9203}, mesh = {*Career Choice ; Entrepreneurship/economics ; *Happiness ; *Job Satisfaction ; *Publishing/economics ; Research Personnel/*economics/*psychology ; *Travel/economics/psychology ; }, } @article {pmid29976827, year = {2018}, author = {McColl, H and Racimo, F and Vinner, L and Demeter, F and Gakuhari, T and Moreno-Mayar, JV and van Driem, G and Gram Wilken, U and Seguin-Orlando, A and de la Fuente Castro, C and Wasef, S and Shoocongdej, R and Souksavatdy, V and Sayavongkhamdy, T and Saidin, MM and Allentoft, ME and Sato, T and Malaspinas, AS and Aghakhanian, FA and Korneliussen, T and Prohaska, A and Margaryan, A and de Barros Damgaard, P and Kaewsutthi, S and Lertrit, P and Nguyen, TMH and Hung, HC and Minh Tran, T and Nghia Truong, H and Nguyen, GH and Shahidan, S and Wiradnyana, K and Matsumae, H and Shigehara, N and Yoneda, M and Ishida, H and Masuyama, T and Yamada, Y and Tajima, A and Shibata, H and Toyoda, A and Hanihara, T and Nakagome, S and Deviese, T and Bacon, AM and Duringer, P and Ponche, JL and Shackelford, L and Patole-Edoumba, E and Nguyen, AT and Bellina-Pryce, B and Galipaud, JC and Kinaston, R and Buckley, H and Pottier, C and Rasmussen, S and Higham, T and Foley, RA and Lahr, MM and Orlando, L and Sikora, M and Phipps, ME and Oota, H and Higham, C and Lambert, DM and Willerslev, E}, title = {The prehistoric peopling of Southeast Asia.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {88-92}, doi = {10.1126/science.aat3628}, pmid = {29976827}, issn = {1095-9203}, mesh = {Asia, Southeastern ; Asian Continental Ancestry Group/genetics ; DNA, Ancient ; Genetic Variation ; *Genome, Human ; History, Ancient ; Human Migration/*history ; Humans ; Population/genetics ; Sequence Analysis, DNA ; }, abstract = {The human occupation history of Southeast Asia (SEA) remains heavily debated. Current evidence suggests that SEA was occupied by Hòabìnhian hunter-gatherers until ~4000 years ago, when farming economies developed and expanded, restricting foraging groups to remote habitats. Some argue that agricultural development was indigenous; others favor the "two-layer" hypothesis that posits a southward expansion of farmers giving rise to present-day Southeast Asian genetic diversity. By sequencing 26 ancient human genomes (25 from SEA, 1 Japanese Jōmon), we show that neither interpretation fits the complexity of Southeast Asian history: Both Hòabìnhian hunter-gatherers and East Asian farmers contributed to current Southeast Asian diversity, with further migrations affecting island SEA and Vietnam. Our results help resolve one of the long-standing controversies in Southeast Asian prehistory.}, } @article {pmid29976826, year = {2018}, author = {Daly, KG and Maisano Delser, P and Mullin, VE and Scheu, A and Mattiangeli, V and Teasdale, MD and Hare, AJ and Burger, J and Verdugo, MP and Collins, MJ and Kehati, R and Erek, CM and Bar-Oz, G and Pompanon, F and Cumer, T and Çakırlar, C and Mohaseb, AF and Decruyenaere, D and Davoudi, H and Çevik, Ö and Rollefson, G and Vigne, JD and Khazaeli, R and Fathi, H and Doost, SB and Rahimi Sorkhani, R and Vahdati, AA and Sauer, EW and Azizi Kharanaghi, H and Maziar, S and Gasparian, B and Pinhasi, R and Martin, L and Orton, D and Arbuckle, BS and Benecke, N and Manica, A and Horwitz, LK and Mashkour, M and Bradley, DG}, title = {Ancient goat genomes reveal mosaic domestication in the Fertile Crescent.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {85-88}, doi = {10.1126/science.aas9411}, pmid = {29976826}, issn = {1095-9203}, mesh = {Africa ; Animals ; Animals, Domestic/classification/genetics ; Asia ; DNA, Ancient ; DNA, Mitochondrial/genetics ; *Domestication ; Europe ; Follistatin/genetics ; Genetic Variation ; Genome ; Goats/classification/*genetics ; *Mosaicism ; Phylogeny ; }, abstract = {Current genetic data are equivocal as to whether goat domestication occurred multiple times or was a singular process. We generated genomic data from 83 ancient goats (51 with genome-wide coverage) from Paleolithic to Medieval contexts throughout the Near East. Our findings demonstrate that multiple divergent ancient wild goat sources were domesticated in a dispersed process that resulted in genetically and geographically distinct Neolithic goat populations, echoing contemporaneous human divergence across the region. These early goat populations contributed differently to modern goats in Asia, Africa, and Europe. We also detect early selection for pigmentation, stature, reproduction, milking, and response to dietary change, providing 8000-year-old evidence for human agency in molding genome variation within a partner species.}, } @article {pmid29976825, year = {2018}, author = {Ní Leathlobhair, M and Perri, AR and Irving-Pease, EK and Witt, KE and Linderholm, A and Haile, J and Lebrasseur, O and Ameen, C and Blick, J and Boyko, AR and Brace, S and Cortes, YN and Crockford, SJ and Devault, A and Dimopoulos, EA and Eldridge, M and Enk, J and Gopalakrishnan, S and Gori, K and Grimes, V and Guiry, E and Hansen, AJ and Hulme-Beaman, A and Johnson, J and Kitchen, A and Kasparov, AK and Kwon, YM and Nikolskiy, PA and Lope, CP and Manin, A and Martin, T and Meyer, M and Myers, KN and Omura, M and Rouillard, JM and Pavlova, EY and Sciulli, P and Sinding, MS and Strakova, A and Ivanova, VV and Widga, C and Willerslev, E and Pitulko, VV and Barnes, I and Gilbert, MTP and Dobney, KM and Malhi, RS and Murchison, EP and Larson, G and Frantz, LAF}, title = {The evolutionary history of dogs in the Americas.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {81-85}, doi = {10.1126/science.aao4776}, pmid = {29976825}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; //European Research Council/International ; }, mesh = {Americas ; Animals ; *Biological Evolution ; Cell Nucleus/genetics ; Dog Diseases/genetics/*transmission ; *Dogs/classification/genetics ; *Domestication ; Genome, Mitochondrial ; Human Migration ; Humans ; Neoplasms/*veterinary ; Phylogeny ; Sexually Transmitted Diseases/transmission/*veterinary ; Siberia ; Wolves/classification/genetics ; }, abstract = {Dogs were present in the Americas before the arrival of European colonists, but the origin and fate of these precontact dogs are largely unknown. We sequenced 71 mitochondrial and 7 nuclear genomes from ancient North American and Siberian dogs from time frames spanning ~9000 years. Our analysis indicates that American dogs were not derived from North American wolves. Instead, American dogs form a monophyletic lineage that likely originated in Siberia and dispersed into the Americas alongside people. After the arrival of Europeans, native American dogs almost completely disappeared, leaving a minimal genetic legacy in modern dog populations. The closest detectable extant lineage to precontact American dogs is the canine transmissible venereal tumor, a contagious cancer clone derived from an individual dog that lived up to 8000 years ago.}, } @article {pmid29976824, year = {2018}, author = {Luo, SX and Huang, J and Li, Q and Mohammad, H and Lee, CY and Krishna, K and Kok, AM and Tan, YL and Lim, JY and Li, H and Yeow, LY and Sun, J and He, M and Grandjean, J and Sajikumar, S and Han, W and Fu, Y}, title = {Regulation of feeding by somatostatin neurons in the tuberal nucleus.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {76-81}, doi = {10.1126/science.aar4983}, pmid = {29976824}, issn = {1095-9203}, mesh = {Animals ; Appetite Regulation/*physiology ; GABAergic Neurons/*physiology ; Ghrelin/physiology ; Mice ; Mice, Mutant Strains ; Paraventricular Hypothalamic Nucleus/cytology/physiology ; Somatostatin/*physiology ; Ventral Thalamic Nuclei/cytology/*physiology ; }, abstract = {The tuberal nucleus (TN) is a surprisingly understudied brain region. We found that somatostatin (SST) neurons in the TN, which is known to exhibit pathological or cytological changes in human neurodegenerative diseases, play a crucial role in regulating feeding in mice. GABAergic tuberal SST (TNSST) neurons were activated by hunger and by the hunger hormone, ghrelin. Activation of TNSST neurons promoted feeding, whereas inhibition reduced it via projections to the paraventricular nucleus and bed nucleus of the stria terminalis. Ablation of TNSST neurons reduced body weight gain and food intake. These findings reveal a previously unknown mechanism of feeding regulation that operates through orexigenic TNSST neurons, providing a new perspective for understanding appetite changes.}, } @article {pmid29976823, year = {2018}, author = {Weber, T and John, S and Tagliabue, A and DeVries, T}, title = {Biological uptake and reversible scavenging of zinc in the global ocean.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {72-76}, doi = {10.1126/science.aap8532}, pmid = {29976823}, issn = {1095-9203}, mesh = {*Climate Change ; Oceans and Seas ; Plankton/*metabolism ; Seawater/*chemistry ; Zinc/analysis/*metabolism ; }, abstract = {Zinc (Zn) is a key micronutrient for marine phytoplankton, with a global distribution that is similar to silicic acid. The processes that govern this relationship, despite the very different biological cycling of Zn and silica, remain poorly understood. Here, we use diagnostic and mechanistic models to show that only a combination of Southern Ocean biological uptake and reversible scavenging of Zn onto sinking particles can explain the observations. The distinction between organic and adsorbed Zn can also reconcile the vertical distribution and mass balance of Zn isotopes, which previously appeared at odds. This holistic understanding explains the Zn deficiencies observed throughout the low-latitude ocean and implies a greater sensitivity of the marine Zn cycle to climate-driven changes in organic matter cycling than previously recognized.}, } @article {pmid29976822, year = {2018}, author = {Pagar, VV and RajanBabu, TV}, title = {Tandem catalysis for asymmetric coupling of ethylene and enynes to functionalized cyclobutanes.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {68-72}, pmid = {29976822}, issn = {1095-9203}, support = {R01 GM108762/GM/NIGMS NIH HHS/United States ; }, abstract = {Transformation of simple precursors into structurally complex cyclobutanes, present in many biologically important natural products and pharmaceuticals, is of considerable interest in medicinal chemistry. Starting from 1,3-enynes and ethylene, both exceptionally inexpensive starting materials, we report a cobalt-catalyzed route to vinylcyclobutenes, as well as the further enantioselective addition of ethylene to these products to form complex cyclobutanes with all-carbon quaternary centers. These reactions can proceed in discrete stages or in a tandem fashion to achieve three highly selective carbon-carbon bond formations in one pot using a single chiral cobalt catalyst.}, } @article {pmid29976821, year = {2018}, author = {Yang, J and Zhu, X and Wolf, TJA and Li, Z and Nunes, JPF and Coffee, R and Cryan, JP and Gühr, M and Hegazy, K and Heinz, TF and Jobe, K and Li, R and Shen, X and Veccione, T and Weathersby, S and Wilkin, KJ and Yoneda, C and Zheng, Q and Martinez, TJ and Centurion, M and Wang, X}, title = {Imaging CF3I conical intersection and photodissociation dynamics with ultrafast electron diffraction.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {64-67}, doi = {10.1126/science.aat0049}, pmid = {29976821}, issn = {1095-9203}, abstract = {Conical intersections play a critical role in excited-state dynamics of polyatomic molecules because they govern the reaction pathways of many nonadiabatic processes. However, ultrafast probes have lacked sufficient spatial resolution to image wave-packet trajectories through these intersections directly. Here, we present the simultaneous experimental characterization of one-photon and two-photon excitation channels in isolated CF3I molecules using ultrafast gas-phase electron diffraction. In the two-photon channel, we have mapped out the real-space trajectories of a coherent nuclear wave packet, which bifurcates onto two potential energy surfaces when passing through a conical intersection. In the one-photon channel, we have resolved excitation of both the umbrella and the breathing vibrational modes in the CF3 fragment in multiple nuclear dimensions. These findings benchmark and validate ab initio nonadiabatic dynamics calculations.}, } @article {pmid29976820, year = {2018}, author = {Rose, BC and Huang, D and Zhang, ZH and Stevenson, P and Tyryshkin, AM and Sangtawesin, S and Srinivasan, S and Loudin, L and Markham, ML and Edmonds, AM and Twitchen, DJ and Lyon, SA and de Leon, NP}, title = {Observation of an environmentally insensitive solid-state spin defect in diamond.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {60-63}, doi = {10.1126/science.aao0290}, pmid = {29976820}, issn = {1095-9203}, abstract = {Engineering coherent systems is a central goal of quantum science. Color centers in diamond are a promising approach, with the potential to combine the coherence of atoms with the scalability of a solid-state platform. We report a color center that shows insensitivity to environmental decoherence caused by phonons and electric field noise: the neutral charge state of silicon vacancy (SiV0). Through careful materials engineering, we achieved >80% conversion of implanted silicon to SiV0 SiV0 exhibits spin-lattice relaxation times approaching 1 minute and coherence times approaching 1 second. Its optical properties are very favorable, with ~90% of its emission into the zero-phonon line and near-transform-limited optical linewidths. These combined properties make SiV0 a promising defect for quantum network applications.}, } @article {pmid29976819, year = {2018}, author = {Sun, S and Kim, H and Luo, Z and Solomon, GS and Waks, E}, title = {A single-photon switch and transistor enabled by a solid-state quantum memory.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {57-60}, doi = {10.1126/science.aat3581}, pmid = {29976819}, issn = {1095-9203}, abstract = {Single-photon switches and transistors generate strong photon-photon interactions that are essential for quantum circuits and networks. However, the deterministic control of an optical signal with a single photon requires strong interactions with a quantum memory, which has been challenging to achieve in a solid-state platform. We demonstrate a single-photon switch and transistor enabled by a solid-state quantum memory. Our device consists of a semiconductor spin qubit strongly coupled to a nanophotonic cavity. The spin qubit enables a single 63-picosecond gate photon to switch a signal field containing up to an average of 27.7 photons before the internal state of the device resets. Our results show that semiconductor nanophotonic devices can produce strong and controlled photon-photon interactions that could enable high-bandwidth photonic quantum information processing.}, } @article {pmid29976818, year = {2018}, author = {Ma, T and Kapustin, EA and Yin, SX and Liang, L and Zhou, Z and Niu, J and Li, LH and Wang, Y and Su, J and Li, J and Wang, X and Wang, WD and Wang, W and Sun, J and Yaghi, OM}, title = {Single-crystal x-ray diffraction structures of covalent organic frameworks.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {48-52}, doi = {10.1126/science.aat7679}, pmid = {29976818}, issn = {1095-9203}, abstract = {The crystallization problem is an outstanding challenge in the chemistry of porous covalent organic frameworks (COFs). Their structural characterization has been limited to modeling and solutions based on powder x-ray or electron diffraction data. Single crystals of COFs amenable to x-ray diffraction characterization have not been reported. Here, we developed a general procedure to grow large single crystals of three-dimensional imine-based COFs (COF-300, hydrated form of COF-300, COF-303, LZU-79, and LZU-111). The high quality of the crystals allowed collection of single-crystal x-ray diffraction data of up to 0.83-angstrom resolution, leading to unambiguous solution and precise anisotropic refinement. Characteristics such as degree of interpenetration, arrangement of water guests, the reversed imine connectivity, linker disorder, and uncommon topology were deciphered with atomic precision-aspects impossible to determine without single crystals.}, } @article {pmid29976817, year = {2018}, author = {Claybrook, J and Kildare, S}, title = {Autonomous vehicles: No driver…no regulation?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {36-37}, doi = {10.1126/science.aau2715}, pmid = {29976817}, issn = {1095-9203}, } @article {pmid29976816, year = {2018}, author = {Navarro, JAR}, title = {The dynamic art of growing COF crystals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {35}, doi = {10.1126/science.aau1701}, pmid = {29976816}, issn = {1095-9203}, } @article {pmid29976815, year = {2018}, author = {Reinberg, D and Vales, LD}, title = {Chromatin domains rich in inheritance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {33-34}, doi = {10.1126/science.aat7871}, pmid = {29976815}, issn = {1095-9203}, mesh = {Animals ; Caenorhabditis elegans/genetics ; Chromatin/*chemistry ; *Epigenesis, Genetic ; *Heredity ; Histones/*chemistry ; Protein Domains ; *Protein Processing, Post-Translational ; Saccharomyces cerevisiae/genetics ; Schizosaccharomyces/genetics ; }, } @article {pmid29976814, year = {2018}, author = {Bellwood, P}, title = {The search for ancient DNA heads east.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {31-32}, doi = {10.1126/science.aat8662}, pmid = {29976814}, issn = {1095-9203}, mesh = {*DNA, Ancient ; *DNA, Mitochondrial ; History, Ancient ; Phylogeny ; }, } @article {pmid29976813, year = {2018}, author = {Fielding, HH}, title = {Molecular movies filmed at conical intersections.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {30-31}, doi = {10.1126/science.aat6002}, pmid = {29976813}, issn = {1095-9203}, mesh = {*Microscopy, Electron, Transmission ; Models, Molecular ; *Quantum Theory ; }, } @article {pmid29976812, year = {2018}, author = {Diano, S}, title = {A new brain circuit in feeding control.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {29-30}, doi = {10.1126/science.aau1419}, pmid = {29976812}, issn = {1095-9203}, mesh = {Brain ; *Central Nervous System ; Feeding Behavior ; *Neural Pathways ; }, } @article {pmid29976811, year = {2018}, author = {Goodman, L and Karlsson, EK}, title = {America's lost dogs.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {27-28}, doi = {10.1126/science.aau1306}, pmid = {29976811}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Dogs/*genetics ; }, } @article {pmid29976810, year = {2018}, author = {Adamowicz, BM and Chong, DHY and Gutiérrez, C and Matz, J and Fer, E and Polat, EO and MacKay, H and Galagedara, R and Coste, A and Pupkaite, J and Farnoud, AM and Murphy, CW and White, ER and Rezic, I and Hartzell, C and Matia, A and Nicola, MV and Isaacson, KJ and Tiv, M and Weinstein, AM and Ch'ng, S and Sweeney, M and Lipkin, A and Chakraborty, S and Sanganyado, E and Anderson, SM and Nguyen, N and Laisk, T and Favaro, B}, title = {Broad interests reap benefits for science.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {24-26}, doi = {10.1126/science.aau3978}, pmid = {29976810}, issn = {1095-9203}, mesh = {Hobbies/*psychology ; Humans ; Research Personnel/*psychology ; Science ; }, } @article {pmid29976809, year = {2018}, author = {Piller, C}, title = {Is FDA's revolving door open too wide?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {21}, doi = {10.1126/science.361.6397.21}, pmid = {29976809}, issn = {1095-9203}, mesh = {Advisory Committees/*economics ; *Conflict of Interest ; Drug Approval/*economics ; United States ; United States Food and Drug Administration ; }, } @article {pmid29976808, year = {2018}, author = {Piller, C}, title = {Hidden conflicts?.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {16-20}, doi = {10.1126/science.361.6397.16}, pmid = {29976808}, issn = {1095-9203}, mesh = {Adenosine/*analogs & derivatives ; Advisory Committees/*economics ; Conflict of Interest/*economics ; *Drug Approval ; Drug Industry/*economics ; Federal Government ; *Purinergic P2Y Receptor Antagonists ; Ticagrelor ; United States ; United States Food and Drug Administration ; }, } @article {pmid29976807, year = {2018}, author = {Cho, A}, title = {Proposed DOE test reactor sparks controversy.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {15}, doi = {10.1126/science.361.6397.15}, pmid = {29976807}, issn = {1095-9203}, } @article {pmid29976806, year = {2018}, author = {Kupferschmidt, K}, title = {Biologists raise alarm over changes to biopiracy rules.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {14}, doi = {10.1126/science.361.6397.14}, pmid = {29976806}, issn = {1095-9203}, } @article {pmid29976805, year = {2018}, author = {Mann, A}, title = {Optical interferometers sharpen views of the sky.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {12-13}, doi = {10.1126/science.361.6397.12}, pmid = {29976805}, issn = {1095-9203}, } @article {pmid29976804, year = {2018}, author = {Mervis, J}, title = {Lawmakers ask NIH and CDC charities for more on donors.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {11-12}, doi = {10.1126/science.361.6397.11}, pmid = {29976804}, issn = {1095-9203}, } @article {pmid29976803, year = {2018}, author = {Roberts, L}, title = {Polio outbreaks in the DRC threaten eradication effort.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {10-11}, doi = {10.1126/science.361.6397.10}, pmid = {29976803}, issn = {1095-9203}, } @article {pmid29976802, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {8-9}, doi = {10.1126/science.361.6397.8}, pmid = {29976802}, issn = {1095-9203}, } @article {pmid29976801, year = {2018}, author = {Berg, J}, title = {Science Advances advancing.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {7}, doi = {10.1126/science.aau6038}, pmid = {29976801}, issn = {1095-9203}, } @article {pmid29976800, year = {2018}, author = {}, title = {Erratum for the Report "Aging and neurodegeneration are associated with increased mutations in single human neurons" by M. A. Lodato, R. E. Rodin, C. L. Bohrson, M. E. Coulter, A. R. Barton, M. Kwon, M. A. Sherman, C. M. Vitzthum, L. J. Luquette, C. N. Yandava, P. Yang, T. W. Chittenden, N. E. Hatem, S. C. Ryu, M. B. Woodworth, P. J. Park, C. A. Walsh.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {}, doi = {10.1126/science.aau6185}, pmid = {29976800}, issn = {1095-9203}, } @article {pmid29976799, year = {2018}, author = {Milovanovic, D and Wu, Y and Bian, X and De Camilli, P}, title = {A liquid phase of synapsin and lipid vesicles.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {604-607}, pmid = {29976799}, issn = {1095-9203}, support = {P30 DA018343/DA/NIDA NIH HHS/United States ; R37 NS036251/NS/NINDS NIH HHS/United States ; }, mesh = {Cerebellum/ultrastructure ; GRB2 Adaptor Protein/chemistry ; Green Fluorescent Proteins/chemistry ; Humans ; Intrinsically Disordered Proteins/chemistry ; Lipids/*chemistry ; Liposomes/chemistry ; Microscopy, Electron ; Phosphorylation ; Synapsins/*chemistry ; Synaptic Vesicles/*chemistry ; Water/*chemistry ; src Homology Domains ; }, abstract = {Neurotransmitter-containing synaptic vesicles (SVs) form tight clusters at synapses. These clusters act as a reservoir from which SVs are drawn for exocytosis during sustained activity. Several components associated with SVs that are likely to help form such clusters have been reported, including synapsin. Here we found that synapsin can form a distinct liquid phase in an aqueous environment. Other scaffolding proteins could coassemble into this condensate but were not necessary for its formation. Importantly, the synapsin phase could capture small lipid vesicles. The synapsin phase rapidly disassembled upon phosphorylation by calcium/calmodulin-dependent protein kinase II, mimicking the dispersion of synapsin 1 that occurs at presynaptic sites upon stimulation. Thus, principles of liquid-liquid phase separation may apply to the clustering of SVs at synapses.}, } @article {pmid29976798, year = {2018}, author = {Kang, JS and Li, M and Wu, H and Nguyen, H and Hu, Y}, title = {Experimental observation of high thermal conductivity in boron arsenide.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {575-578}, doi = {10.1126/science.aat5522}, pmid = {29976798}, issn = {1095-9203}, abstract = {Improving the thermal management of small-scale devices requires developing materials with high thermal conductivities. The semiconductor boron arsenide (BAs) is an attractive target because of ab initio calculation indicating that single crystals have an ultrahigh thermal conductivity. We synthesized BAs single crystals without detectable defects and measured a room-temperature thermal conductivity of 1300 watts per meter-kelvin. Our spectroscopy study, in conjunction with atomistic theory, reveals that the distinctive band structure of BAs allows for very long phonon mean free paths and strong high-order anharmonicity through the four-phonon process. The single-crystal BAs has better thermal conductivity than other metals and semiconductors. Our study establishes BAs as a benchmark material for thermal management applications and exemplifies the power of combining experiments and ab initio theory in new materials discovery.}, } @article {pmid29976797, year = {2018}, author = {Tian, F and Song, B and Chen, X and Ravichandran, NK and Lv, Y and Chen, K and Sullivan, S and Kim, J and Zhou, Y and Liu, TH and Goni, M and Ding, Z and Sun, J and Udalamatta Gamage, GAG and Sun, H and Ziyaee, H and Huyan, S and Deng, L and Zhou, J and Schmidt, AJ and Chen, S and Chu, CW and Huang, PY and Broido, D and Shi, L and Chen, G and Ren, Z}, title = {Unusual high thermal conductivity in boron arsenide bulk crystals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {582-585}, doi = {10.1126/science.aat7932}, pmid = {29976797}, issn = {1095-9203}, abstract = {Conventional theory predicts that ultrahigh lattice thermal conductivity can only occur in crystals composed of strongly bonded light elements, and that it is limited by anharmonic three-phonon processes. We report experimental evidence that departs from these long-held criteria. We measured a local room-temperature thermal conductivity exceeding 1000 watts per meter-kelvin and an average bulk value reaching 900 watts per meter-kelvin in bulk boron arsenide (BAs) crystals, where boron and arsenic are light and heavy elements, respectively. The high values are consistent with a proposal for phonon-band engineering and can only be explained by higher-order phonon processes. These findings yield insight into the physics of heat conduction in solids and show BAs to be the only known semiconductor with ultrahigh thermal conductivity.}, } @article {pmid29976796, year = {2018}, author = {Li, S and Zheng, Q and Lv, Y and Liu, X and Wang, X and Huang, PY and Cahill, DG and Lv, B}, title = {High thermal conductivity in cubic boron arsenide crystals.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {579-581}, doi = {10.1126/science.aat8982}, pmid = {29976796}, issn = {1095-9203}, abstract = {The high density of heat generated in power electronics and optoelectronic devices is a critical bottleneck in their application. New materials with high thermal conductivity are needed to effectively dissipate heat and thereby enable enhanced performance of power controls, solid-state lighting, communication, and security systems. We report the experimental discovery of high thermal conductivity at room temperature in cubic boron arsenide (BAs) grown through a modified chemical vapor transport technique. The thermal conductivity of BAs, 1000 ± 90 watts per meter per kelvin meter-kelvin, is higher than that of silicon carbide by a factor of 3 and is surpassed only by diamond and the basal-plane value of graphite. This work shows that BAs represents a class of ultrahigh-thermal conductivity materials predicted by a recent theory, and that it may constitute a useful thermal management material for high-power density electronic devices.}, } @article {pmid29976795, year = {2018}, author = {Mura, A and Adriani, A and Connerney, JEP and Bolton, S and Altieri, F and Bagenal, F and Bonfond, B and Dinelli, BM and Gérard, JC and Greathouse, T and Grodent, D and Levin, S and Mauk, B and Moriconi, ML and Saur, J and Waite, JH and Amoroso, M and Cicchetti, A and Fabiano, F and Filacchione, G and Grassi, D and Migliorini, A and Noschese, R and Olivieri, A and Piccioni, G and Plainaki, C and Sindoni, G and Sordini, R and Tosi, F and Turrini, D}, title = {Juno observations of spot structures and a split tail in Io-induced aurorae on Jupiter.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {774-777}, doi = {10.1126/science.aat1450}, pmid = {29976795}, issn = {1095-9203}, abstract = {Jupiter's aurorae are produced in its upper atmosphere when incoming high-energy electrons precipitate along the planet's magnetic field lines. A northern and a southern main auroral oval are visible, surrounded by small emission features associated with the Galilean moons. We present infrared observations, obtained with the Juno spacecraft, showing that in the case of Io, this emission exhibits a swirling pattern that is similar in appearance to a von Kármán vortex street. Well downstream of the main auroral spots, the extended tail is split in two. Both of Ganymede's footprints also appear as a pair of emission features, which may provide a remote measure of Ganymede's magnetosphere. These features suggest that the magnetohydrodynamic interaction between Jupiter and its moon is more complex than previously anticipated.}, } @article {pmid29976794, year = {2018}, author = {Du, M and Chen, ZJ}, title = {DNA-induced liquid phase condensation of cGAS activates innate immune signaling.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6403}, pages = {704-709}, doi = {10.1126/science.aat1022}, pmid = {29976794}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cells, Cultured ; DNA/*metabolism ; Fibroblasts ; Humans ; *Immunity, Innate ; Mice ; Nucleotides, Cyclic/*biosynthesis ; Nucleotidyltransferases/*metabolism ; Phase Transition ; Protein Binding ; Signal Transduction ; Zinc/metabolism ; }, abstract = {The binding of DNA to cyclic GMP-AMP synthase (cGAS) leads to the production of the secondary messenger cyclic GMP-AMP (cGAMP), which activates innate immune responses. We have shown that DNA binding to cGAS robustly induced the formation of liquidlike droplets in which cGAS was activated. The disordered and positively charged cGAS N terminus enhanced cGAS-DNA phase separation by increasing the valencies of DNA binding. Long DNA was more efficient in promoting cGAS liquid phase separation and cGAS enzyme activity than short DNA. Moreover, free zinc ions enhanced cGAS enzyme activity both in vitro and in cells by promoting cGAS-DNA phase separation. These results demonstrated that the DNA-induced phase transition of cGAS promotes cGAMP production and innate immune signaling.}, } @article {pmid29976249, year = {2018}, author = {Kayani, MUR and Doyle, SM and Sangwan, N and Wang, G and Gilbert, JA and Christner, BC and Zhu, TF}, title = {Metagenomic analysis of basal ice from an Alaskan glacier.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {123}, pmid = {29976249}, issn = {2049-2618}, mesh = {Alaska ; Bacteria/*classification/genetics/*isolation & purification/metabolism ; Base Sequence ; Biodiversity ; Ecosystem ; Genome, Bacterial/*genetics ; Geologic Sediments/*microbiology ; Ice Cover/*microbiology ; *Metagenomics ; Microbiota/*genetics ; Nitrification/genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfur/metabolism ; }, abstract = {BACKGROUND: Glaciers cover ~ 10% of land but are among the least explored environments on Earth. The basal portion of glaciers often harbors unique aquatic microbial ecosystems in the absence of sunlight, and knowledge on the microbial community structures and their metabolic potential is very limited. Here, we provide insights into the microbial lifestyle present at the base of the Matanuska Glacier, Alaska.

RESULTS: DNA and RNA were extracted from samples of the Matanuska Glacier basal ice. Using Illumina MiSeq and HiSeq sequencing, we investigated the microbial diversity with the metagenomic shotgun reads and 16S ribosomal RNA data. We further assembled 9 partial and draft bacterial genomes from the metagenomic assembly, and identified key metabolic pathways such as sulfur oxidation and nitrification. Collectively, our analyses suggest a prevalence of lithotrophic and heterotrophic metabolisms in the subglacial microbiome.

CONCLUSION: Our results present the first metagenomic assembly and bacterial draft genomes for a subglacial environment. These results extend our understanding of the chemical and biological processes in subglacial environments critically influenced by global climate change.}, } @article {pmid29976198, year = {2018}, author = {McKenna, A and Shendure, J}, title = {FlashFry: a fast and flexible tool for large-scale CRISPR target design.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {74}, pmid = {29976198}, issn = {1741-7007}, support = {DP1 HG007811/HG/NHGRI NIH HHS/United States ; T32 HL007312/HL/NHLBI NIH HHS/United States ; R01HG006283/HG/NHGRI NIH HHS/United States ; T32HL007312/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {BACKGROUND: Genome-wide knockout studies, noncoding deletion scans, and other large-scale studies require a simple and lightweight framework that can quickly discover and score thousands of candidate CRISPR guides targeting an arbitrary DNA sequence. While several CRISPR web applications exist, there is a need for a high-throughput tool to rapidly discover and process hundreds of thousands of CRISPR targets.

RESULTS: Here, we introduce FlashFry, a fast and flexible command-line tool for characterizing large numbers of CRISPR target sequences. With FlashFry, users can specify an unconstrained number of mismatches to putative off-targets, richly annotate discovered sites, and tag potential guides with commonly used on-target and off-target scoring metrics. FlashFry runs at speeds comparable to commonly used genome-wide sequence aligners, and output is provided as an easy-to-manipulate text file.

CONCLUSIONS: FlashFry is a fast and convenient command-line tool to discover and score CRISPR targets within large DNA sequences.}, } @article {pmid29976179, year = {2018}, author = {Yan, H and Zhang, J and Wen, J and Wang, Y and Niu, W and Teng, Z and Zhao, T and Dai, Y and Zhang, Y and Wang, C and Qin, Y and Xia, G and Zhang, H}, title = {CDC42 controls the activation of primordial follicles by regulating PI3K signaling in mouse oocytes.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {73}, pmid = {29976179}, issn = {1741-7007}, abstract = {BACKGROUND: In mammalian females, progressive activation of dormant primordial follicles in adulthood is crucial for the maintenance of the reproductive lifespan. Misregulated activation of primordial follicles leads to various ovarian diseases, such as premature ovarian insufficiency (POI). Although recent studies have revealed that several functional genes and pathways, such as phosphoinositide 3-kinase (PI3K) signaling, play roles in controlling the activation of primordial follicles, our understanding of the molecular networks regulating the activation progress is still incomplete.

RESULTS: Here, we identify a new role for cell division cycle 42 (CDC42) in regulating the activation of primordial follicles in mice. Our results show that CDC42 expression increases in oocytes during the activation of primordial follicles in the ovary. Disruption of CDC42 activity with specific inhibitors or knockdown of Cdc42 expression significantly suppresses primordial follicle activation in cultured mouse ovaries. Conversely, the follicle activation ratio is remarkably increased by overexpression of CDC42 in ovaries. We further demonstrate that CDC42 governs the process of primordial follicle activation by binding to phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (p110β) and regulating the expression levels of PTEN in oocytes. Finally, we extend our study to potential clinical applications and show that a short-term in vitro treatment with CDC42 activators could significantly increase the activation rates of primordial follicles in both neonatal and adult mouse ovaries.

CONCLUSION: Our results reveal that CDC42 controls the activation of primordial follicles in the mammalian ovary and that increasing the activity of CDC42 with specific activators might improve the efficiency of in vitro activation approaches, opening avenues for infertility treatments.}, } @article {pmid29976163, year = {2018}, author = {Mommert, M and Tabone, O and Oriol, G and Cerrato, E and Guichard, A and Naville, M and Fournier, P and Volff, JN and Pachot, A and Monneret, G and Venet, F and Brengel-Pesce, K and Textoris, J and Mallet, F}, title = {LTR-retrotransposon transcriptome modulation in response to endotoxin-induced stress in PBMCs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {522}, pmid = {29976163}, issn = {1471-2164}, mesh = {Computational Biology ; Endogenous Retroviruses/genetics ; Humans ; Immune System/drug effects/metabolism ; Leukocytes, Mononuclear/cytology/*drug effects/metabolism ; Lipopolysaccharides/*pharmacology ; Retroelements/*genetics ; Terminal Repeat Sequences/*genetics ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: Human Endogenous Retroviruses (HERVs) and Mammalian apparent LTR-retrotransposons (MaLRs) represent the 8% of our genome and are distributed among our 46 chromosomes. These LTR-retrotransposons are thought to be essentially silent except in cancer, autoimmunity and placental development. Their Long Terminal Repeats (LTRs) constitute putative promoter or polyA regulatory sequences. In this study, we used a recently described high-density microarray which can be used to study HERV/MaLR transcriptome including 353,994 HERV/MaLR loci and 1559 immunity-related genes.

RESULTS: We described, for the first time, the HERV transcriptome in peripheral blood mononuclear cells (PBMCs) using a cellular model mimicking inflammatory response and monocyte anergy observed after septic shock. About 5.6% of the HERV/MaLR repertoire is transcribed in PBMCs. Roughly one-tenth [5.7-13.1%] of LTRs exhibit a putative constitutive promoter or polyA function while one-quarter [19.5-27.6%] may shift from silent to active. Evidence was given that some HERVs/MaLRs and genes may share similar regulation control under lipopolysaccharide (LPS) stimulation conditions. Stimulus-dependent response confirms that HERV expression is tightly regulated in PBMCs. Altogether, these observations make it possible to integrate 62 HERVs/MaLRs and 26 genes in 11 canonical pathways and suggest a link between HERV expression and immune response. The transcriptional modulation of HERVs located close to genes such as OAS2/3 and IFI44/IFI44L or at a great distance from genes was discussed.

CONCLUSION: This microarray-based approach revealed the expression of about 47,466 distinct HERV loci and identified 951 putative promoter LTRs and 744 putative polyA LTRs in PBMCs. HERV/MaLR expression was shown to be tightly modulated under several stimuli including high-dose and low-dose LPS and Interferon-γ (IFN-γ). HERV incorporation at the crossroads of immune response pathways paves the way for further functional studies and analyses of the HERV transcriptome in altered immune responses in vivo such as in sepsis.}, } @article {pmid29976148, year = {2018}, author = {Kessi, M and Peng, J and Yang, L and Xiong, J and Duan, H and Pang, N and Yin, F}, title = {Genetic etiologies of the electrical status epilepticus during slow wave sleep: systematic review.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {40}, pmid = {29976148}, issn = {1471-2156}, support = {NO. 2016YFC1306202, NO. 2016YFC0904400//National Key Research and Development Program of China/ ; NO. 2016YFC1306202, NO. 2016YFC0904400//National Key Research and Development Program of China/ ; NO. 2016YFC1306202, NO. 2016YFC0904400//National Key Research and Development Program of China/ ; NO. 2016YFC1306202, NO. 2016YFC0904400//National Key Research and Development Program of China/ ; NO. 2016YFC1306202, NO. 2016YFC0904400//National Key Research and Development Program of China/ ; NO. 2016YFC1306202, NO. 2016YFC0904400//National Key Research and Development Program of China/ ; NO. 2016YFC1306202, NO. 2016YFC0904400//National Key Research and Development Program of China/ ; NO. 81370771//National Natural Science Foundation of China/ ; NO. 81370771//National Natural Science Foundation of China/ ; NO. 81370771//National Natural Science Foundation of China/ ; NO. 81370771//National Natural Science Foundation of China/ ; NO. 81370771//National Natural Science Foundation of China/ ; NO. 81370771//National Natural Science Foundation of China/ ; NO. 81370771//National Natural Science Foundation of China (CN)/ ; }, abstract = {BACKGROUND: Electrical status epilepticus during slow-wave sleep (ESESS) which is also known as continuous spike-wave of slow sleep (CSWSS) is type of electroencephalographic (EEG) pattern which is seen in ESESS/CSWSS/epilepsy aphasia spectrum. This EEG pattern can occur alone or with other syndromes. Its etiology is not clear, however, brain malformations, immune disorders, and genetic etiologies are suspected to contribute. We aimed to perform a systematic review of all genetic etiologies which have been reported to associate with ESESS/CSWSS/epilepsy-aphasia spectrum. We further aimed to identify the common underlying pathway which can explain it. To our knowledge, there is no available systematic review of genetic etiologies of ESESS/CSWSS/epilepsy-aphasia spectrum. MEDLINE, EMBASE, PubMed and Cochrane review database were searched, using terms specific to electrical status epilepticus during sleep or continuous spike-wave discharges during slow sleep or epilepsy-aphasia spectrum and of studies of genetic etiologies. These included monogenic mutations and copy number variations (CNVs). For each suspected dosage-sensitive gene, further studies were performed through OMIM and PubMed database.

RESULTS: Twenty-six studies out of the 136 identified studies satisfied our inclusion criteria. I51 cases were identified among those 26 studies. 16 studies reported 11 monogenic mutations: SCN2A (N = 6), NHE6/SLC9A6 (N = 1), DRPLA/ ATN1 (N = 1), Neuroserpin/SRPX2 (N = 1), OPA3 (N = 1), KCNQ2 (N = 2), KCNA2 (N = 5), GRIN2A (N = 34), CNKSR2 (N = 2), SLC6A1 (N = 2) and KCNB1 (N = 5). 10 studies reported 89 CNVs including 9 recurrent ones: Xp22.12 deletion encompassing CNKSR2 (N = 6), 16p13 deletion encompassing GRIN2A (N = 4), 15q11.2-13.1 duplication (N = 15), 3q29 duplication (N = 11), 11p13 duplication (N = 2), 10q21.3 deletion (N = 2), 3q25 deletion (N = 2), 8p23.3 deletion (N = 2) and 9p24.2 (N = 2). 68 of the reported genetic etiologies including monogenic mutations and CNVs were detected in patients with ESESS/CSWSS/epilepsy aphasia spectrum solely. The most common underlying pathway was channelopathy (N = 56).

CONCLUSIONS: Our review suggests that genetic etiologies have a role to play in the occurrence of ESESS/CSWSS/epilepsy-aphasia spectrum. The common underlying pathway is channelopathy. Therefore we propose more genetic studies to be done for more discoveries which can pave a way for proper drug identification. We also suggest development of common cut-off value for spike-wave index to ensure common language among clinicians and researchers.}, } @article {pmid29976145, year = {2018}, author = {Somervuo, P and Koskinen, P and Mei, P and Holm, L and Auvinen, P and Paulin, L}, title = {BARCOSEL: a tool for selecting an optimal barcode set for high-throughput sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {257}, pmid = {29976145}, issn = {1471-2105}, abstract = {BACKGROUND: Current high-throughput sequencing platforms provide capacity to sequence multiple samples in parallel. Different samples are labeled by attaching a short sample specific nucleotide sequence, barcode, to each DNA molecule prior pooling them into a mix containing a number of libraries to be sequenced simultaneously. After sequencing, the samples are binned by identifying the barcode sequence within each sequence read. In order to tolerate sequencing errors, barcodes should be sufficiently apart from each other in sequence space. An additional constraint due to both nucleotide usage and basecalling accuracy is that the proportion of different nucleotides should be in balance in each barcode position. The number of samples to be mixed in each sequencing run may vary and this introduces a problem how to select the best subset of available barcodes at sequencing core facility for each sequencing run. There are plenty of tools available for de novo barcode design, but they are not suitable for subset selection.

RESULTS: We have developed a tool which can be used for three different tasks: 1) selecting an optimal barcode set from a larger set of candidates, 2) checking the compatibility of user-defined set of barcodes, e.g. whether two or more libraries with existing barcodes can be combined in a single sequencing pool, and 3) augmenting an existing set of barcodes. In our approach the selection process is formulated as a minimization problem. We define the cost function and a set of constraints and use integer programming to solve the resulting combinatorial problem. Based on the desired number of barcodes to be selected and the set of candidate sequences given by user, the necessary constraints are automatically generated and the optimal solution can be found. The method is implemented in C programming language and web interface is available at http://ekhidna2.biocenter.helsinki.fi/barcosel .

CONCLUSIONS: Increasing capacity of sequencing platforms raises the challenge of mixing barcodes. Our method allows the user to select a given number of barcodes among the larger existing barcode set so that both sequencing errors are tolerated and the nucleotide balance is optimized. The tool is easy to access via web browser.}, } @article {pmid29976144, year = {2018}, author = {Li, H and Harwood, JD and Liu, T and Chu, D}, title = {Novel proteome and acetylome of Bemisia tabaci Q in response to Cardinium infection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {523}, pmid = {29976144}, issn = {1471-2164}, support = {31572064//National Natural Science Foundation of China/ ; }, mesh = {Acetylation ; Animals ; Bacteroidetes/*physiology ; Chromatography, High Pressure Liquid ; Hemiptera/*metabolism/microbiology ; Insect Proteins/genetics/metabolism ; Lysine/metabolism ; Peptides/analysis ; Protein Interaction Maps/genetics ; Proteome/*metabolism ; Symbiosis ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: It has become increasingly clear that symbionts have crucial evolutionary and ecological ramifications for their host arthropods. However, little is known whether these symbiont infections influence the proteome and lysine acetylome of their host arthropods. Here we performed experiments to investigate the proteomes and acetylomes of Cardinium-infected (C*+) and -uninfected (C-) Bemisia tabaci Q with identical backgrounds, through the combination of affinity enrichment and high-resolution LC-MS/MS analysis.

RESULTS: Of the 3353 proteins whose levels were quantitated in proteome, a total of 146 proteins dividing into 77 up-regulated and 69 down-regulated proteins were discovered to be differentially expressed as having at least a 1.2-fold change when C*+ strain was compared with C- strain. Furthermore, a total of 528 lysine acetylation sites in 283 protein groups were identified, among which 356 sites in 202 proteins were quantified. The comparison of acetylomes revealed 30 sites in 26 lysine acetylation proteins (Kac) were quantified as up-regulated targets and 35 sites in 29 Kac proteins were quantified as down-regulated targets. Functional analysis showed that these differentially expressed proteins and Kac proteins were mainly involved in diverse physiological processes related to development, immune responses and energy metabolism, such as retinol metabolism, methane metabolism and fatty acid degradation. Notably, protein interaction network analyses demonstrated widespread interactions modulated by protein acetylation.

CONCLUSION: Here we show the proteome and acetylom of B. tabaci Q in response to the symbiont Cardinium infection. This is the first study to utilize the tool of acetylome analysis for revealing physiological responses of arthropods to its symbiont infection, which will provide an important resource for exploring the arthropod-symbiont interaction.}, } @article {pmid29976143, year = {2018}, author = {Villarreal, P and Carrasco, M and Barahona, S and Alcaíno, J and Cifuentes, V and Baeza, M}, title = {Antarctic yeasts: analysis of their freeze-thaw tolerance and production of antifreeze proteins, fatty acids and ergosterol.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {66}, pmid = {29976143}, issn = {1471-2180}, abstract = {BACKGROUND: Microorganisms have evolved a number of mechanisms to thrive in cold environments, including the production of antifreeze proteins, high levels of polyunsaturated fatty acids, and ergosterol. In this work, several yeast species isolated from Antarctica were analyzed with respect to their freeze-thaw tolerance and production of the three abovementioned compounds, which may also have economic importance.

RESULTS: The freeze-thaw tolerance of yeasts was widely variable among species, and a clear correlation with the production of any of the abovementioned compounds was not observed. Antifreeze proteins that were partially purified from Goffeauzyma gastrica maintained their antifreeze activities after several freeze-thaw cycles. A relatively high volumetric production of ergosterol was observed in the yeasts Vishniacozyma victoriae, G. gastrica and Leucosporidium creatinivorum, i.e., 19, 19 and 16 mg l- 1, respectively. In addition, a high percentage of linoleic acid with respect to total fatty acids was observed in V. victoriae (10%), Wickerhamomyces anomalus (12%) and G. gastrica (13%), and a high percentage of alpha linoleic acid was observed in L. creatinivorum (3.3%).

CONCLUSIONS: Given these results, the abovementioned yeasts are good candidates to be evaluated for use in the production of antifreeze proteins, fatty acids, and ergosterol at the industrial scale.}, } @article {pmid29976142, year = {2018}, author = {Scherbaum, S and Hellmann, N and Fernández, R and Pick, C and Burmester, T}, title = {Diversity, evolution, and function of myriapod hemocyanins.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {107}, pmid = {29976142}, issn = {1471-2148}, support = {Bu956/9//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Amino Acid Sequence ; Animals ; Arthropods/classification/*genetics ; Base Sequence ; Binding Sites ; Copper/metabolism ; *Evolution, Molecular ; *Genetic Variation ; Hemocyanins/chemistry/*genetics/metabolism ; Monophenol Monooxygenase/metabolism ; Oxygen/metabolism ; Phylogeny ; Protein Subunits/chemistry/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; }, abstract = {BACKGROUND: Hemocyanin transports O2 in the hemolymph of many arthropod species. Such respiratory proteins have long been considered unnecessary in Myriapoda. As a result, the presence of hemocyanin in Myriapoda has long been overlooked. We analyzed transcriptome and genome sequences from all major myriapod taxa - Chilopoda, Diplopoda, Symphyla, and Pauropoda - with the aim of identifying hemocyanin-like proteins.

RESULTS: We investigated the genomes and transcriptomes of 56 myriapod species and identified 46 novel full-length hemocyanin subunit sequences in 20 species of Chilopoda, Diplopoda, and Symphyla, but not Pauropoda. We found in Cleidogona sp. (Diplopoda, Chordeumatida) a hemocyanin-like sequence with mutated copper-binding centers, which cannot bind O2. An RNA-seq approach showed markedly different hemocyanin mRNA levels from ~ 6 to 25,000 reads per kilobase per million reads. To evaluate the contribution of hemocyanin to O2 transport, we specifically studied the hemocyanin of the centipede Scolopendra dehaani. This species harbors two distinct hemocyanin subunits with low expression levels. We showed cooperative O2 binding in the S. dehaani hemolymph, indicating that hemocyanin supports O2 transport even at low concentration. Further, we demonstrated that hemocyanin is > 1500-fold more highly expressed in the fertilized egg than in the adult.

CONCLUSION: Hemocyanin was most likely the respiratory protein in the myriapod stem-lineage, but multiple taxa may have independently lost hemocyanin and thus the ability of efficient O2 transport. In myriapods, hemocyanin is much more widespread than initially appreciated. Some myriapods express hemocyanin only at low levels, which are, nevertheless, sufficient for O2 supply. Notably, also in myriapods, a non-respiratory protein similar to insect storage hexamerins evolved from the hemocyanin.}, } @article {pmid29976139, year = {2018}, author = {Wang, R and Sun, L and Wang, Y and Deng, Y and Fang, Z and Liu, Y and Deng, Q and Sun, D and Gooneratne, R}, title = {Influence of food matrix type on extracellular products of Vibrio parahaemolyticus.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {65}, pmid = {29976139}, issn = {1471-2180}, abstract = {BACKGROUND: Two strains of Vibrio parahaemolyticus (ATCC 17802 and 33847) in shrimp, oyster, freshwater fish, pork, chicken and egg fried rice were evaluated for production of hemolysin and exoenzymes of potential importance to the pathogenicity of this bacterium.

RESULTS: The two strains of V. parahaemolyticus produced hemolysin, gelatinase, caseinase, phospholipase, urease, DNase and amylase in selected food matrices. Significantly higher (p < 0.05) hemolytic activity was produced by V. parahaemolyticus in egg fried rice > shrimp > freshwater fish > chicken > oyster > pork. But the exoenzyme activities were not consistent with the hemolytic activity profile, being significantly higher (p < 0.05) in shrimp > freshwater fish > chicken > oyster > pork > egg fried rice. Filtrates of V. parahaemolyticus from shrimp, freshwater fish and chicken given intraperitoneally to adult mice induced marked liver and kidney damage and were highly lethal compared with the filtrates of V. parahaemolyticus from oyster > egg fried rice > pork.

CONCLUSION: From in vitro and in vivo tests, it appears that the food matrix type has a significant impact on the activity of extracellular products and the pathogenicity of V. parahaemolyticus. From a food safety aspect, it is important to determine which food matrices can stimulate V. parahaemolyticus to produce additional extracellular factors. This is the first report of non-seafood including freshwater fish and chicken contaminated with V. parahaemolyticus to have been shown to be toxic to mice in vivo.}, } @article {pmid29976136, year = {2018}, author = {Dinarelli, S and Girasole, M and Longo, G}, title = {FC_analysis: a tool for investigating atomic force microscopy maps of force curves.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {258}, pmid = {29976136}, issn = {1471-2105}, abstract = {BACKGROUND: The collection and analysis of Atomic Force Microscopy force curves is a well-established procedure to obtain high-resolution information of non-topographic data from any kind of sample, including biological specimens. In particular, these analyses are commonly employed to study elasticity, stiffness or adhesion properties of the samples. Furthermore, the collection of several force curves over an extended area of the specimens allows reconstructing maps, called force volume maps, of the spatial distribution of the mechanical properties. Coupling these maps with the conventional high-resolution topographic reconstruction of the sample's surface, provides a deeper insight on the sample composition from the structural and nanomechanical point of view.

RESULTS: In this paper we present the open source software package FC_analysis that automatically analyses single force curves or entire force volume maps to yield the corresponding elasticity and deformability images. The principal characteristic of the FC_analysis is a large adaptability to the various experimental setups and to different analysis methodologies. For instance, the user can provide custom values for the detector sensitivity, scanner-z sensitivity, cantilever's elastic constant and map's acquisition modality and can choose between different analysis methodologies. Furthermore, the software allows the optimization of the fitting parameters and gives direct control on each step of the analysis procedure. Notably, to overcome a limitation common to many other analysis programs, FC_analysis can be applied to a rectangular portion of the image, allowing the analysis of inhomogeneous samples. Finally, the software allows reconstructing a Young's modulus map at different penetration depths, enabling the use of modern investigation tools such as the force tomography.

CONCLUSIONS: The FC_analysis software aims to become a useful tool for the analysis of force curves maps collected using custom or commercial Atomic Force Microscopes, and is especially useful in those cases for which the producer doesn't release a dedicated software.}, } @article {pmid29975590, year = {2018}, author = {Josling, GA and Williamson, KC and Llinás, M}, title = {Regulation of Sexual Commitment and Gametocytogenesis in Malaria Parasites.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {501-519}, doi = {10.1146/annurev-micro-090817-062712}, pmid = {29975590}, issn = {1545-3251}, support = {R01 AI069314/AI/NIAID NIH HHS/United States ; }, abstract = {Sexual differentiation of malaria parasites from the asexual blood stage into gametocytes is an essential part of the life cycle, as gametocytes are the form that is taken up by the mosquito host. Because of the essentiality of this process for transmission to the mosquito, gametocytogenesis is an extremely attractive target for therapeutic interventions. The subject of this review is the considerable progress that has been made in recent years in elucidating the molecular mechanisms governing this important differentiation process. In particular, a number of critical transcription factors and epigenetic regulators have emerged as crucial elements in the regulation of commitment. The identification of these factors has allowed us to understand better than ever before the events occurring prior to and during commitment to sexual development and offers potential for new therapeutic interventions.}, } @article {pmid29975449, year = {2018}, author = {Llonga, N and Ylla, G and Bau, J and Belles, X and Piulachs, MD}, title = {Diversity of piRNA expression patterns during the ontogeny of the German cockroach.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {5}, pages = {288-295}, doi = {10.1002/jez.b.22815}, pmid = {29975449}, issn = {1552-5015}, abstract = {The Piwi-interacting RNA (piRNA) system is an evolutionarily conserved mechanism involved in the control of transposable elements and maintenance of genomic stability, especially in germ line cells and in early embryo stages. However, relevant particularities, both in mechanism and function, exist across species among metazoans and even within the insect class. As a member of the scarcely studied hemimetabolan group, Blattella germanica can be a suitable reference model to study insect evolution. We present the results of a stringent process of identification and study of expressed piRNAs for B. germanica across 11 developmental stages, ranging from unfertilized egg to nymphs and adult female. Our results confirm the dual origin of piRNA in this species, with a majority of them being generated from the primary pathway, and a smaller but highly expressed set of sequences participating in the secondary ("ping-pong") reamplification pathway. An intriguing partial complementarity in expression is observed between the piRNA of the two biogenesis pathways, with those generated in the secondary pathway being quite restricted to early embryo stages. In addition, many piRNAs are exclusively expressed in late embryo and nymphal stages. These observations point at piRNA functions beyond the role of transposon control in early embryogenesis. Our work supports the view of a more complex scenario, with different sets of piRNAs acting in different times and having a range of functions wider than previously thought.}, } @article {pmid29975186, year = {2018}, author = {Révész, F and Tóth, EM and Kriszt, B and Bóka, K and Benedek, T and Sárkány, O and Nagy, Z and Táncsics, A}, title = {Sphingobium aquiterrae sp. nov., a toluene, meta- and para-xylene-degrading bacterium isolated from petroleum hydrocarbon-contaminated groundwater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2807-2812}, doi = {10.1099/ijsem.0.002898}, pmid = {29975186}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Groundwater/*microbiology ; Hungary ; Nucleic Acid Hybridization ; Petroleum/metabolism ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/chemistry ; Sphingomonadaceae/*classification/genetics/isolation & purification ; Toluene/metabolism ; Ubiquinone/analogs & derivatives/chemistry ; Water Pollutants, Chemical/*metabolism ; Xylenes/metabolism ; }, abstract = {A Gram-negative, aerobic, slightly yellow-pigmented bacterium, designated as SKLS-A10T, was isolated from groundwater sample of the 'Siklós' petroleum hydrocarbon contaminated site (Hungary). Phylogenetic analysis based on 16S rRNA gene sequence revealed that strain SKLS-A10T formed a distinct phyletic lineage within the genus Sphingobium. It shared the highest 16S rRNA gene homology with Sphingobium abikonense DSM 23268T (97.29 %), followed by Sphingobium lactosutens DSM 23389T (97.23 %), Sphingobium phenoxybenzoativorans KCTC 42448T (97.16 %) and Sphingobium subterraneum NBRC 109814T (96.74 %). The predominant fatty acids (>5 % of the total) are C18 : 1ω7c, C14 : 0 2-OH, C16 : 1ω7c/iso C15 : 0 2-OH, C17 : 1ω6c and C16 : 0. The major ubiquinone is Q-10. The predominant polyamine is spermidine. The major polar lipids are sphingoglycolipid and diphosphatidylglycerol. The DNA G+C content of strain SKLS-A10T is 65.9 mol%. On the basis of evidence from this taxonomic study using a polyphasic approach, strain SKLS-A10T represents a novel species of the genus Sphingobium for which the name Sphingobiumaquiterrae sp. nov. is proposed. The type strain is SKLS-A10T (=DSM 106441T=NCAIM B. 02634T).}, } @article {pmid29974612, year = {2018}, author = {Parizadeh, L and Tourbiez, D and Garcia, C and Haffner, P and Dégremont, L and Le Roux, F and Travers, MA}, title = {Ecologically realistic model of infection for exploring the host damage caused by Vibrio aestuarianus.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4343-4355}, doi = {10.1111/1462-2920.14350}, pmid = {29974612}, issn = {1462-2920}, support = {//IFREMER and Poitou-Charente Region/ ; OPOPOP project, 13-ADAP-0007-01//ANR/ ; H2020 n°678589//European commission/ ; }, abstract = {Although vibrios are frequently associated with marine organisms mortality outbreaks, knowledge on their ecology and pathogenicity is sparse, thus limiting disease management and prophylactic strategies. Here, we investigated V. aestuarianus infection onset and progression in the wild, taking advantage of a 'claire' pond: a semi-closed system with limited seawater renewal, theoretically more adapted to disease transmission. We showed a positive association of the bacteria with oysters, which can constitute a reservoir for the bacteria in the winter. Moreover, passage through oysters was found to be necessary for experimental disease reproduction as vibrios shedding from diseased oysters have higher infectivity than from in vitro grown. We next developed an experimental 'ecologically realistic' infection model in a mesocosm, allowing infection by natural route. By means of this non-invasive protocol, we analysed the pathogenesis of the bacteria and demonstrated the importance of haemolymph for initial colonization and the septicaemic nature of this disease.}, } @article {pmid29974361, year = {2018}, author = {McNulty, SM and Sullivan, BA}, title = {Alpha satellite DNA biology: finding function in the recesses of the genome.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {3}, pages = {115-138}, pmid = {29974361}, issn = {1573-6849}, support = {R01 GM124041/GM/NIGMS NIH HHS/United States ; DGE-1644868//National Science Foundation/International ; R01 GM124041/NH/NIH HHS/United States ; }, mesh = {Animals ; DNA, Satellite/genetics/*metabolism ; Genome, Human/*physiology ; Humans ; Kinetochores/*metabolism ; RNA, Untranslated/genetics/*metabolism ; Transcriptome/*physiology ; }, abstract = {Repetitive DNA, formerly referred to by the misnomer "junk DNA," comprises a majority of the human genome. One class of this DNA, alpha satellite, comprises up to 10% of the genome. Alpha satellite is enriched at all human centromere regions and is competent for de novo centromere assembly. Because of the highly repetitive nature of alpha satellite, it has been difficult to achieve genome assemblies at centromeres using traditional next-generation sequencing approaches, and thus, centromeres represent gaps in the current human genome assembly. Moreover, alpha satellite DNA is transcribed into repetitive noncoding RNA and contributes to a large portion of the transcriptome. Recent efforts to characterize these transcripts and their function have uncovered pivotal roles for satellite RNA in genome stability, including silencing "selfish" DNA elements and recruiting centromere and kinetochore proteins. This review will describe the genomic and epigenetic features of alpha satellite DNA, discuss recent findings of noncoding transcripts produced from distinct alpha satellite arrays, and address current progress in the functional understanding of this oft-neglected repetitive sequence. We will discuss unique challenges of studying human satellite DNAs and RNAs and point toward new technologies that will continue to advance our understanding of this largely untapped portion of the genome.}, } @article {pmid29974176, year = {2018}, author = {Zagrobelny, M and Jensen, MK and Vogel, H and Feyereisen, R and Bak, S}, title = {Evolution of the Biosynthetic Pathway for Cyanogenic Glucosides in Lepidoptera.}, journal = {Journal of molecular evolution}, volume = {86}, number = {6}, pages = {379-394}, pmid = {29974176}, issn = {1432-1432}, support = {DFF-1323-00088//Natur og Univers, Det Frie Forskningsråd/ ; }, abstract = {Cyanogenic glucosides are widespread defence compounds in plants, and they are also found in some arthropods, especially within Lepidoptera. The aliphatic linamarin and lotaustralin are the most common cyanogenic glucosides in Lepidoptera, and they are biosynthesised de novo, and/or sequestered from food plants. Their biosynthetic pathway was elucidated in the burnet moth, Zygaena filipendulae, and consists of three enzymes: two cytochrome P450 enzymes, CYP405A2 and CYP332A3, and a glucosyl transferase, UGT33A1. Heliconius butterflies also produce linamarin and lotaustralin and have close homologs to CYP405A2 and CYP332A3. To unravel the evolution of the pathway in Lepidoptera, we performed phylogenetic analyses on all available CYP405 and CYP332 sequences. CYP332 sequences were present in almost all Lepidoptera, while the distribution of CYP405s among butterflies and moths was much more limited. Negative purifying selection was found in both CYP enzyme families, indicating that the biosynthesis of CNglcs is an old trait, and not a newly evolved pathway. We compared CYP405A2 to its close paralog, CYP405A3, which is not involved in the biosynthetic pathway. The only significant difference between these two enzymes is a smaller substrate binding pocket in CYP405A2, which would make the enzyme more substrate specific. We consider it likely that the biosynthetic pathway of CNglcs in butterflies and moths have evolved from a common pathway, perhaps based on a predisposition for detoxifying aldoximes by way of a CYP332. Later the aldoxime metabolising CYP405s evolved, and a UGT was recruited into the pathway to establish de novo biosynthesis of CNglcs.}, } @article {pmid29973737, year = {2018}, author = {Shen, H}, title = {The labs growing human embryos for longer than ever before.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {19-22}, doi = {10.1038/d41586-018-05586-z}, pmid = {29973737}, issn = {1476-4687}, mesh = {Animals ; Blastomeres/cytology ; Developmental Biology/ethics/methods/*trends ; Embryo Culture Techniques/ethics/methods/*trends ; Embryo Research/ethics ; Embryo, Mammalian/cytology/embryology ; Embryoid Bodies/cytology ; *Embryonic Development/genetics ; Female ; Fertilization in Vitro ; Fetal Development ; Fetus/cytology/embryology ; Gastrulation ; Gene Editing ; Human Embryonic Stem Cells/cytology ; Humans ; Imaging, Three-Dimensional ; Mice ; Octamer Transcription Factor-3/genetics ; Organizers, Embryonic/cytology/embryology ; Pregnancy ; Time Factors ; }, } @article {pmid29973736, year = {2018}, author = {}, title = {Microscope damage, reef recovery and disappearing trees.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {10-11}, doi = {10.1038/d41586-018-05608-w}, pmid = {29973736}, issn = {1476-4687}, } @article {pmid29973735, year = {2018}, author = {Bai, X}, title = {Advance the ecosystem approach in cities.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {7}, doi = {10.1038/d41586-018-05607-x}, pmid = {29973735}, issn = {1476-4687}, mesh = {*Cities/economics ; Climate Change ; Conservation of Natural Resources/economics/methods/*trends ; *Ecosystem ; Humans ; Public Health/methods/trends ; Trees/growth & development ; Urban Population/statistics & numerical data/*trends ; }, } @article {pmid29973734, year = {2018}, author = {Lebel, J and McLean, R}, title = {A better measure of research from the global south.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {23-26}, doi = {10.1038/d41586-018-05581-4}, pmid = {29973734}, issn = {1476-4687}, mesh = {*Communication Barriers ; Egypt ; India ; Journal Impact Factor ; *Peer Review, Research ; Research/*standards ; *Research Design ; Research Personnel/standards ; *Social Change ; *Stakeholder Participation ; }, } @article {pmid29973733, year = {2018}, author = {Archibald, AM and Gusinskaia, NV and Hessels, JWT and Deller, AT and Kaplan, DL and Lorimer, DR and Lynch, RS and Ransom, SM and Stairs, IH}, title = {Universality of free fall from the orbital motion of a pulsar in a stellar triple system.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {73-76}, doi = {10.1038/s41586-018-0265-1}, pmid = {29973733}, issn = {1476-4687}, abstract = {Einstein's theory of gravity-the general theory of relativity1-is based on the universality of free fall, which specifies that all objects accelerate identically in an external gravitational field. In contrast to almost all alternative theories of gravity2, the strong equivalence principle of general relativity requires universality of free fall to apply even to bodies with strong self-gravity. Direct tests of this principle using Solar System bodies3,4 are limited by the weak self-gravity of the bodies, and tests using pulsar-white-dwarf binaries5,6 have been limited by the weak gravitational pull of the Milky Way. PSR J0337+1715 is a hierarchical system of three stars (a stellar triple system) in which a binary consisting of a millisecond radio pulsar and a white dwarf in a 1.6-day orbit is itself in a 327-day orbit with another white dwarf. This system permits a test that compares how the gravitational pull of the outer white dwarf affects the pulsar, which has strong self-gravity, and the inner white dwarf. Here we report that the accelerations of the pulsar and its nearby white-dwarf companion differ fractionally by no more than 2.6 × 10-6. For a rough comparison, our limit on the strong-field Nordtvedt parameter, which measures violation of the universality of free fall, is a factor of ten smaller than that obtained from (weak-field) Solar System tests3,4 and a factor of almost a thousand smaller than that obtained from other strong-field tests5,6.}, } @article {pmid29973732, year = {2018}, author = {Schildgen, TF and van der Beek, PA and Sinclair, HD and Thiede, RC}, title = {Spatial correlation bias in late-Cenozoic erosion histories derived from thermochronology.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {89-93}, doi = {10.1038/s41586-018-0260-6}, pmid = {29973732}, issn = {1476-4687}, abstract = {The potential link between erosion rates at the Earth's surface and changes in global climate has intrigued geoscientists for decades1,2 because such a coupling has implications for the influence of silicate weathering3,4 and organic-carbon burial5 on climate and for the role of Quaternary glaciations in landscape evolution1,6. A global increase in late-Cenozoic erosion rates in response to a cooling, more variable climate has been proposed on the basis of worldwide sedimentation rates7. Other studies have indicated, however, that global erosion rates may have remained steady, suggesting that the reported increases in sediment-accumulation rates are due to preservation biases, depositional hiatuses and varying measurement intervals8-10. More recently, a global compilation of thermochronology data has been used to infer a nearly twofold increase in the erosion rate in mountainous landscapes over late-Cenozoic times6. It has been contended that this result is free of the biases that affect sedimentary records11, although others have argued that it contains biases related to how thermochronological data are averaged12 and to erosion hiatuses in glaciated landscapes13. Here we investigate the 30 locations with reported accelerated erosion during the late Cenozoic6. Our analysis shows that in 23 of these locations, the reported increases are a result of a spatial correlation bias-that is, combining data with disparate exhumation histories, thereby converting spatial erosion-rate variations into temporal increases. In four locations, the increases can be explained by changes in tectonic boundary conditions. In three cases, climatically induced accelerations are recorded, driven by localized glacial valley incision. Our findings suggest that thermochronology data currently have insufficient resolution to assess whether late-Cenozoic climate change affected erosion rates on a global scale. We suggest that a synthesis of local findings that include location-specific information may help to further investigate drivers of global erosion rates.}, } @article {pmid29973731, year = {2018}, author = {Thal, DM and Glukhova, A and Sexton, PM and Christopoulos, A}, title = {Structural insights into G-protein-coupled receptor allostery.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {45-53}, doi = {10.1038/s41586-018-0259-z}, pmid = {29973731}, issn = {1476-4687}, mesh = {*Allosteric Regulation/drug effects ; Animals ; Binding Sites/drug effects ; Cytosol ; Humans ; Models, Molecular ; Protein Conformation/drug effects ; Protein Multimerization/drug effects ; Receptors, G-Protein-Coupled/agonists/*chemistry/classification/*metabolism ; }, abstract = {G-protein-coupled receptors (GPCRs) are key cell-surface proteins that transduce external environmental cues into biochemical signals across the membrane. GPCRs are intrinsically allosteric proteins; they interact via spatially distinct yet conformationally linked domains with both endogenous and exogenous proteins, nutrients, metabolites, hormones, small molecules and biological agents. Here we explore recent high-resolution structural studies, which are beginning to unravel the atomic details of allosteric transitions that govern GPCR biology, as well as highlighting how the wide diversity of druggable allosteric sites across these receptors present opportunities for developing new classes of therapeutics.}, } @article {pmid29973729, year = {2018}, author = {van der Linde, S and Suz, LM and Orme, CDL and Cox, F and Andreae, H and Asi, E and Atkinson, B and Benham, S and Carroll, C and Cools, N and De Vos, B and Dietrich, HP and Eichhorn, J and Gehrmann, J and Grebenc, T and Gweon, HS and Hansen, K and Jacob, F and Kristofel, F and Lech, P and Manninger, M and Martin, J and Meesenburg, H and Merila, P and Nicolas, M and Pavlenda, P and Rautio, P and Schaub, M and Schrock, HW and Seidling, W and Šramek, V and Thimonier, A and Thomsen, IM and Titeux, H and Vanguelova, E and Verstraeten, A and Vesterdal, L and Waldner, P and Wijk, S and Zhang, Y and Žlindra, D and Bidartondo, MI}, title = {Author Correction: Environment and host as large-scale controls of ectomycorrhizal fungi.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {E42}, doi = {10.1038/s41586-018-0312-y}, pmid = {29973729}, issn = {1476-4687}, abstract = {Change history: In the HTML version of this Article, author 'Filipa Cox' had no affiliation in the author list, although she was correctly associated with affiliation 3 in the PDF. In addition, the blue circles for 'oak' were missing from Extended Data Fig. 1. These errors have been corrected online.}, } @article {pmid29973728, year = {2018}, author = {Zhang, L and Bailey, JB and Subramanian, RH and Groisman, A and Tezcan, FA}, title = {Author Correction: Hyperexpandable, self-healing macromolecular crystals with integrated polymer networks.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {E31}, doi = {10.1038/s41586-018-0283-z}, pmid = {29973728}, issn = {1476-4687}, support = {T32 GM112584/GM/NIGMS NIH HHS/United States ; }, abstract = {Change history: In this Letter, Alexander Groisman should have been listed as an author. This error has been corrected online.}, } @article {pmid29973727, year = {2018}, author = {Cherry, KM and Qian, L}, title = {Scaling up molecular pattern recognition with DNA-based winner-take-all neural networks.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {370-376}, doi = {10.1038/s41586-018-0289-6}, pmid = {29973727}, issn = {1476-4687}, abstract = {From bacteria following simple chemical gradients1 to the brain distinguishing complex odour information2, the ability to recognize molecular patterns is essential for biological organisms. This type of information-processing function has been implemented using DNA-based neural networks3, but has been limited to the recognition of a set of no more than four patterns, each composed of four distinct DNA molecules. Winner-take-all computation4 has been suggested5,6 as a potential strategy for enhancing the capability of DNA-based neural networks. Compared to the linear-threshold circuits7 and Hopfield networks8 used previously3, winner-take-all circuits are computationally more powerful4, allow simpler molecular implementation and are not constrained by the number of patterns and their complexity, so both a large number of simple patterns and a small number of complex patterns can be recognized. Here we report a systematic implementation of winner-take-all neural networks based on DNA-strand-displacement9,10 reactions. We use a previously developed seesaw DNA gate motif3,11,12, extended to include a simple and robust component that facilitates the cooperative hybridization13 that is involved in the process of selecting a 'winner'. We show that with this extended seesaw motif DNA-based neural networks can classify patterns into up to nine categories. Each of these patterns consists of 20 distinct DNA molecules chosen from the set of 100 that represents the 100 bits in 10 × 10 patterns, with the 20 DNA molecules selected tracing one of the handwritten digits '1' to '9'. The network successfully classified test patterns with up to 30 of the 100 bits flipped relative to the digit patterns 'remembered' during training, suggesting that molecular circuits can robustly accomplish the sophisticated task of classifying highly complex and noisy information on the basis of similarity to a memory.}, } @article {pmid29973726, year = {2018}, author = {Rabosky, DL and Chang, J and Title, PO and Cowman, PF and Sallan, L and Friedman, M and Kaschner, K and Garilao, C and Near, TJ and Coll, M and Alfaro, ME}, title = {An inverse latitudinal gradient in speciation rate for marine fishes.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {392-395}, doi = {10.1038/s41586-018-0273-1}, pmid = {29973726}, issn = {1476-4687}, abstract = {Far more species of organisms are found in the tropics than in temperate and polar regions, but the evolutionary and ecological causes of this pattern remain controversial1,2. Tropical marine fish communities are much more diverse than cold-water fish communities found at higher latitudes3,4, and several explanations for this latitudinal diversity gradient propose that warm reef environments serve as evolutionary 'hotspots' for species formation5-8. Here we test the relationship between latitude, species richness and speciation rate across marine fishes. We assembled a time-calibrated phylogeny of all ray-finned fishes (31,526 tips, of which 11,638 had genetic data) and used this framework to describe the spatial dynamics of speciation in the marine realm. We show that the fastest rates of speciation occur in species-poor regions outside the tropics, and that high-latitude fish lineages form new species at much faster rates than their tropical counterparts. High rates of speciation occur in geographical regions that are characterized by low surface temperatures and high endemism. Our results reject a broad class of mechanisms under which the tropics serve as an evolutionary cradle for marine fish diversity and raise new questions about why the coldest oceans on Earth are present-day hotspots of species formation.}, } @article {pmid29973725, year = {2018}, author = {Su, T and Stanley, G and Sinha, R and D'Amato, G and Das, S and Rhee, S and Chang, AH and Poduri, A and Raftrey, B and Dinh, TT and Roper, WA and Li, G and Quinn, KE and Caron, KM and Wu, S and Miquerol, L and Butcher, EC and Weissman, I and Quake, S and Red-Horse, K}, title = {Single-cell analysis of early progenitor cells that build coronary arteries.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {356-362}, pmid = {29973725}, issn = {1476-4687}, support = {R01 HL128503/HL/NHLBI NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; T32 HL098049/HL/NHLBI NIH HHS/United States ; R01 GM037734/GM/NIGMS NIH HHS/United States ; R01 AI130471/AI/NIAID NIH HHS/United States ; }, abstract = {Arteries and veins are specified by antagonistic transcriptional programs. However, during development and regeneration, new arteries can arise from pre-existing veins through a poorly understood process of cell fate conversion. Here, using single-cell RNA sequencing and mouse genetics, we show that vein cells of the developing heart undergo an early cell fate switch to create a pre-artery population that subsequently builds coronary arteries. Vein cells underwent a gradual and simultaneous switch from venous to arterial fate before a subset of cells crossed a transcriptional threshold into the pre-artery state. Before the onset of coronary blood flow, pre-artery cells appeared in the immature vessel plexus, expressed mature artery markers, and decreased cell cycling. The vein-specifying transcription factor COUP-TF2 (also known as NR2F2) prevented plexus cells from overcoming the pre-artery threshold by inducing cell cycle genes. Thus, vein-derived coronary arteries are built by pre-artery cells that can differentiate independently of blood flow upon the release of inhibition mediated by COUP-TF2 and cell cycle factors.}, } @article {pmid29973724, year = {2018}, author = {Rai, AK and Chen, JX and Selbach, M and Pelkmans, L}, title = {Kinase-controlled phase transition of membraneless organelles in mitosis.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {211-216}, doi = {10.1038/s41586-018-0279-8}, pmid = {29973724}, issn = {1476-4687}, mesh = {Anaphase-Promoting Complex-Cyclosome/metabolism ; Cytoplasm/metabolism ; Cytoplasmic Granules/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; *Mitosis ; Nuclear Envelope/metabolism ; Organelles/*metabolism ; Poly(A)-Binding Protein I/metabolism ; Protein Binding ; Protein Transport ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/biosynthesis/*metabolism ; Protein-Tyrosine Kinases/antagonists & inhibitors/biosynthesis/*metabolism ; Solubility ; Spindle Apparatus/metabolism ; Stress, Physiological ; }, abstract = {Liquid-liquid phase separation has been shown to underlie the formation and disassembly of membraneless organelles in cells, but the cellular mechanisms that control this phenomenon are poorly understood. A prominent example of regulated and reversible segregation of liquid phases may occur during mitosis, when membraneless organelles disappear upon nuclear-envelope breakdown and reappear as mitosis is completed. Here we show that the dual-specificity kinase DYRK3 acts as a central dissolvase of several types of membraneless organelle during mitosis. DYRK3 kinase activity is essential to prevent the unmixing of the mitotic cytoplasm into aberrant liquid-like hybrid organelles and the over-nucleation of spindle bodies. Our work supports a mechanism in which the dilution of phase-separating proteins during nuclear-envelope breakdown and the DYRK3-dependent degree of their solubility combine to allow cells to dissolve and condense several membraneless organelles during mitosis.}, } @article {pmid29973723, year = {2018}, author = {Haag, SM and Gulen, MF and Reymond, L and Gibelin, A and Abrami, L and Decout, A and Heymann, M and van der Goot, FG and Turcatti, G and Behrendt, R and Ablasser, A}, title = {Targeting STING with covalent small-molecule inhibitors.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {269-273}, doi = {10.1038/s41586-018-0287-8}, pmid = {29973723}, issn = {1476-4687}, mesh = {Animals ; Binding Sites ; Cell Line ; Cysteine/metabolism ; Golgi Apparatus/drug effects/metabolism ; Hereditary Autoinflammatory Diseases/drug therapy/metabolism ; Humans ; Lipoylation/drug effects ; Membrane Proteins/*antagonists & inhibitors ; Mice ; Mice, Inbred C57BL ; Protein Binding/drug effects ; Signal Transduction/drug effects ; Small Molecule Libraries/analysis/*chemistry/metabolism/*pharmacology ; }, abstract = {Aberrant activation of innate immune pathways is associated with a variety of diseases. Progress in understanding the molecular mechanisms of innate immune pathways has led to the promise of targeted therapeutic approaches, but the development of drugs that act specifically on molecules of interest remains challenging. Here we report the discovery and characterization of highly potent and selective small-molecule antagonists of the stimulator of interferon genes (STING) protein, which is a central signalling component of the intracellular DNA sensing pathway1,2. Mechanistically, the identified compounds covalently target the predicted transmembrane cysteine residue 91 and thereby block the activation-induced palmitoylation of STING. Using these inhibitors, we show that the palmitoylation of STING is essential for its assembly into multimeric complexes at the Golgi apparatus and, in turn, for the recruitment of downstream signalling factors. The identified compounds and their derivatives reduce STING-mediated inflammatory cytokine production in both human and mouse cells. Furthermore, we show that these small-molecule antagonists attenuate pathological features of autoinflammatory disease in mice. In summary, our work uncovers a mechanism by which STING can be inhibited pharmacologically and demonstrates the potential of therapies that target STING for the treatment of autoinflammatory disease.}, } @article {pmid29973722, year = {2018}, author = {Li, N and Lam, WH and Zhai, Y and Cheng, J and Cheng, E and Zhao, Y and Gao, N and Tye, BK}, title = {Structure of the origin recognition complex bound to DNA replication origin.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {217-222}, doi = {10.1038/s41586-018-0293-x}, pmid = {29973722}, issn = {1476-4687}, mesh = {Base Sequence ; *Cryoelectron Microscopy ; DNA/chemistry/genetics/metabolism/ultrastructure ; Minichromosome Maintenance Proteins/metabolism ; Models, Molecular ; Origin Recognition Complex/*chemistry/metabolism/*ultrastructure ; Protein Subunits/chemistry/metabolism ; *Replication Origin ; *Saccharomyces cerevisiae/chemistry/ultrastructure ; Substrate Specificity ; }, abstract = {The six-subunit origin recognition complex (ORC) binds to DNA to mark the site for the initiation of replication in eukaryotes. Here we report a 3 Å cryo-electron microscopy structure of the Saccharomyces cerevisiae ORC bound to a 72-base-pair origin DNA sequence that contains the ARS consensus sequence (ACS) and the B1 element. The ORC encircles DNA through extensive interactions with both phosphate backbone and bases, and bends DNA at the ACS and B1 sites. Specific recognition of thymine residues in the ACS is carried out by a conserved basic amino acid motif of Orc1 in the minor groove, and by a species-specific helical insertion motif of Orc4 in the major groove. Moreover, similar insertions into major and minor grooves are also embedded in the B1 site by basic patch motifs from Orc2 and Orc5, respectively, to contact bases and to bend DNA. This work pinpoints a conserved role of ORC in modulating DNA structure to facilitate origin selection and helicase loading in eukaryotes.}, } @article {pmid29973721, year = {2018}, author = {Borges da Silva, H and Beura, LK and Wang, H and Hanse, EA and Gore, R and Scott, MC and Walsh, DA and Block, KE and Fonseca, R and Yan, Y and Hippen, KL and Blazar, BR and Masopust, D and Kelekar, A and Vulchanova, L and Hogquist, KA and Jameson, SC}, title = {The purinergic receptor P2RX7 directs metabolic fitness of long-lived memory CD8+ T cells.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {264-268}, pmid = {29973721}, issn = {1476-4687}, support = {R01 AI075168/AI/NIAID NIH HHS/United States ; R56 AI075168/AI/NIAID NIH HHS/United States ; R01 CA157971/CA/NCI NIH HHS/United States ; R29 AI038903/AI/NIAID NIH HHS/United States ; T32 GM008471/GM/NIGMS NIH HHS/United States ; R01 CA072669/CA/NCI NIH HHS/United States ; R01 AI038903/AI/NIAID NIH HHS/United States ; R37 AI038903/AI/NIAID NIH HHS/United States ; }, mesh = {AMP-Activated Protein Kinases/metabolism ; Animals ; CD8-Positive T-Lymphocytes/*cytology/enzymology/immunology/*metabolism ; Cells, Cultured ; Enzyme Activation ; Female ; Homeostasis ; Humans ; *Immunologic Memory ; Mice ; Mice, Inbred C57BL ; Mitochondria/physiology ; Receptors, Purinergic P2X7/deficiency/genetics/*metabolism ; }, abstract = {Extracellular ATP (eATP) is an ancient 'danger signal' used by eukaryotes to detect cellular damage1. In mice and humans, the release of eATP during inflammation or injury stimulates both innate immune activation and chronic pain through the purinergic receptor P2RX72-4. It is unclear, however, whether this pathway influences the generation of immunological memory, a hallmark of the adaptive immune system that constitutes the basis of vaccines and protective immunity against re-infection5,6. Here we show that P2RX7 is required for the establishment, maintenance and functionality of long-lived central and tissue-resident memory CD8+ T cell populations in mice. By contrast, P2RX7 is not required for the generation of short-lived effector CD8+ T cells. Mechanistically, P2RX7 promotes mitochondrial homeostasis and metabolic function in differentiating memory CD8+ T cells, at least in part by inducing AMP-activated protein kinase. Pharmacological inhibitors of P2RX7 provoked dysregulated metabolism and differentiation of activated mouse and human CD8+ T cells in vitro, and transient P2RX7 blockade in vivo ameliorated neuropathic pain but also compromised production of CD8+ memory T cells. These findings show that activation of P2RX7 by eATP provides a common currency that both alerts the nervous and immune system to tissue damage, and promotes the metabolic fitness and survival of the most durable and functionally relevant memory CD8+ T cell populations.}, } @article {pmid29973720, year = {2018}, author = {Alfieri, C and Chang, L and Barford, D}, title = {Mechanism for remodelling of the cell cycle checkpoint protein MAD2 by the ATPase TRIP13.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {274-278}, pmid = {29973720}, issn = {1476-4687}, support = {A14109//Cancer Research UK/United Kingdom ; MC_UP_1201/6//Medical Research Council/United Kingdom ; }, mesh = {ATPases Associated with Diverse Cellular Activities/chemistry/*metabolism/ultrastructure ; Apoproteins/chemistry/metabolism/ultrastructure ; Binding Sites ; Biocatalysis/drug effects ; Cdc20 Proteins/chemistry/metabolism/ultrastructure ; Cell Cycle Proteins/chemistry/*metabolism/ultrastructure ; Cryoelectron Microscopy ; Humans ; M Phase Cell Cycle Checkpoints/drug effects ; Mad2 Proteins/*chemistry/*metabolism/ultrastructure ; Models, Molecular ; Protein Conformation ; Spindle Apparatus/drug effects ; Substrate Specificity ; }, abstract = {The maintenance of genome stability during mitosis is coordinated by the spindle assembly checkpoint (SAC) through its effector the mitotic checkpoint complex (MCC), an inhibitor of the anaphase-promoting complex (APC/C, also known as the cyclosome)1,2. Unattached kinetochores control MCC assembly by catalysing a change in the topology of the β-sheet of MAD2 (an MCC subunit), thereby generating the active closed MAD2 (C-MAD2) conformer3-5. Disassembly of free MCC, which is required for SAC inactivation and chromosome segregation, is an ATP-dependent process driven by the AAA+ ATPase TRIP13. In combination with p31comet, an SAC antagonist6, TRIP13 remodels C-MAD2 into inactive open MAD2 (O-MAD2)7-10. Here, we present a mechanism that explains how TRIP13-p31comet disassembles the MCC. Cryo-electron microscopy structures of the TRIP13-p31comet-C-MAD2-CDC20 complex reveal that p31comet recruits C-MAD2 to a defined site on the TRIP13 hexameric ring, positioning the N terminus of C-MAD2 (MAD2NT) to insert into the axial pore of TRIP13 and distorting the TRIP13 ring to initiate remodelling. Molecular modelling suggests that by gripping MAD2NT within its axial pore, TRIP13 couples sequential ATP-driven translocation of its hexameric ring along MAD2NT to push upwards on, and simultaneously rotate, the globular domains of the p31comet-C-MAD2 complex. This unwinds a region of the αA helix of C-MAD2 that is required to stabilize the C-MAD2 β-sheet, thus destabilizing C-MAD2 in favour of O-MAD2 and dissociating MAD2 from p31comet. Our study provides insights into how specific substrates are recruited to AAA+ ATPases through adaptor proteins and suggests a model of how translocation through the axial pore of AAA+ ATPases is coupled to protein remodelling.}, } @article {pmid29973719, year = {2018}, author = {Brochado, AR and Telzerow, A and Bobonis, J and Banzhaf, M and Mateus, A and Selkrig, J and Huth, E and Bassler, S and Zamarreño Beas, J and Zietek, M and Ng, N and Foerster, S and Ezraty, B and Py, B and Barras, F and Savitski, MM and Bork, P and Göttig, S and Typas, A}, title = {Species-specific activity of antibacterial drug combinations.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {259-263}, pmid = {29973719}, issn = {1476-4687}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Benzaldehydes/pharmacology ; Colistin/pharmacology ; Drug Combinations ; Drug Interactions ; Drug Resistance, Microbial/drug effects ; Drug Resistance, Multiple, Bacterial/drug effects ; Drug Synergism ; Escherichia coli/classification/drug effects ; Food Additives/pharmacology ; Gram-Negative Bacteria/*classification/*drug effects ; Larva/drug effects/microbiology ; Microbial Sensitivity Tests ; Moths/growth & development/microbiology ; Phylogeny ; Pseudomonas aeruginosa/classification/drug effects ; Salmonella typhimurium/classification/drug effects ; Species Specificity ; }, abstract = {The spread of antimicrobial resistance has become a serious public health concern, making once-treatable diseases deadly again and undermining the achievements of modern medicine1,2. Drug combinations can help to fight multi-drug-resistant bacterial infections, yet they are largely unexplored and rarely used in clinics. Here we profile almost 3,000 dose-resolved combinations of antibiotics, human-targeted drugs and food additives in six strains from three Gram-negative pathogens-Escherichia coli, Salmonella enterica serovar Typhimurium and Pseudomonas aeruginosa-to identify general principles for antibacterial drug combinations and understand their potential. Despite the phylogenetic relatedness of the three species, more than 70% of the drug-drug interactions that we detected are species-specific and 20% display strain specificity, revealing a large potential for narrow-spectrum therapies. Overall, antagonisms are more common than synergies and occur almost exclusively between drugs that target different cellular processes, whereas synergies are more conserved and are enriched in drugs that target the same process. We provide mechanistic insights into this dichotomy and further dissect the interactions of the food additive vanillin. Finally, we demonstrate that several synergies are effective against multi-drug-resistant clinical isolates in vitro and during infections of the larvae of the greater wax moth Galleria mellonella, with one reverting resistance to the last-resort antibiotic colistin.}, } @article {pmid29973718, year = {2018}, author = {Hilbe, C and Šimsa, Š and Chatterjee, K and Nowak, MA}, title = {Evolution of cooperation in stochastic games.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {246-249}, doi = {10.1038/s41586-018-0277-x}, pmid = {29973718}, issn = {1476-4687}, mesh = {*Biological Evolution ; *Cooperative Behavior ; Decision Making ; Feedback, Psychological ; *Game Theory ; Group Processes ; Probability ; Stochastic Processes ; }, abstract = {Social dilemmas occur when incentives for individuals are misaligned with group interests1-7. According to the 'tragedy of the commons', these misalignments can lead to overexploitation and collapse of public resources. The resulting behaviours can be analysed with the tools of game theory8. The theory of direct reciprocity9-15 suggests that repeated interactions can alleviate such dilemmas, but previous work has assumed that the public resource remains constant over time. Here we introduce the idea that the public resource is instead changeable and depends on the strategic choices of individuals. An intuitive scenario is that cooperation increases the public resource, whereas defection decreases it. Thus, cooperation allows the possibility of playing a more valuable game with higher payoffs, whereas defection leads to a less valuable game. We analyse this idea using the theory of stochastic games16-19 and evolutionary game theory. We find that the dependence of the public resource on previous interactions can greatly enhance the propensity for cooperation. For these results, the interaction between reciprocity and payoff feedback is crucial: neither repeated interactions in a constant environment nor single interactions in a changing environment yield similar cooperation rates. Our framework shows which feedbacks between exploitation and environment-either naturally occurring or designed-help to overcome social dilemmas.}, } @article {pmid29973717, year = {2018}, author = {Zimmermann, M and Murina, O and Reijns, MAM and Agathanggelou, A and Challis, R and Tarnauskaitė, Ž and Muir, M and Fluteau, A and Aregger, M and McEwan, A and Yuan, W and Clarke, M and Lambros, MB and Paneesha, S and Moss, P and Chandrashekhar, M and Angers, S and Moffat, J and Brunton, VG and Hart, T and de Bono, J and Stankovic, T and Jackson, AP and Durocher, D}, title = {CRISPR screens identify genomic ribonucleotides as a source of PARP-trapping lesions.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {285-289}, pmid = {29973717}, issn = {1476-4687}, support = {MC_PC_U127580972//Medical Research Council/United Kingdom ; }, mesh = {Animals ; BRCA1 Protein/deficiency/genetics ; *CRISPR-Cas Systems ; Cell Line ; *DNA Damage/drug effects ; DNA Repair/genetics ; DNA Replication ; DNA Topoisomerases, Type I/metabolism ; Female ; *Gene Editing ; Genes, BRCA1 ; Genome/genetics ; HeLa Cells ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy/enzymology/genetics/pathology ; Male ; Mice ; Neoplasms/drug therapy/enzymology/*genetics/*pathology ; Phthalazines/pharmacology ; Piperazines/pharmacology ; Poly (ADP-Ribose) Polymerase-1/deficiency/genetics/*metabolism ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Prostatic Neoplasms/drug therapy/enzymology/pathology ; Ribonuclease H/deficiency/genetics/metabolism ; Ribonucleotides/*genetics ; Synthetic Lethal Mutations ; Xenograft Model Antitumor Assays ; }, abstract = {The observation that BRCA1- and BRCA2-deficient cells are sensitive to inhibitors of poly(ADP-ribose) polymerase (PARP) has spurred the development of cancer therapies that use these inhibitors to target deficiencies in homologous recombination1. The cytotoxicity of PARP inhibitors depends on PARP trapping, the formation of non-covalent protein-DNA adducts composed of inhibited PARP1 bound to DNA lesions of unclear origins1-4. To address the nature of such lesions and the cellular consequences of PARP trapping, we undertook three CRISPR (clustered regularly interspersed palindromic repeats) screens to identify genes and pathways that mediate cellular resistance to olaparib, a clinically approved PARP inhibitor1. Here we present a high-confidence set of 73 genes, which when mutated cause increased sensitivity to PARP inhibitors. In addition to an expected enrichment for genes related to homologous recombination, we discovered that mutations in all three genes encoding ribonuclease H2 sensitized cells to PARP inhibition. We establish that the underlying cause of the PARP-inhibitor hypersensitivity of cells deficient in ribonuclease H2 is impaired ribonucleotide excision repair5. Embedded ribonucleotides, which are abundant in the genome of cells deficient in ribonucleotide excision repair, are substrates for cleavage by topoisomerase 1, resulting in PARP-trapping lesions that impede DNA replication and endanger genome integrity. We conclude that genomic ribonucleotides are a hitherto unappreciated source of PARP-trapping DNA lesions, and that the frequent deletion of RNASEH2B in metastatic prostate cancer and chronic lymphocytic leukaemia could provide an opportunity to exploit these findings therapeutically.}, } @article {pmid29973716, year = {2018}, author = {Smakowska-Luzan, E and Mott, GA and Parys, K and Stegmann, M and Howton, TC and Layeghifard, M and Neuhold, J and Lehner, A and Kong, J and Grünwald, K and Weinberger, N and Satbhai, SB and Mayer, D and Busch, W and Madalinski, M and Stolt-Bergner, P and Provart, NJ and Mukhtar, MS and Zipfel, C and Desveaux, D and Guttman, DS and Belkhadir, Y}, title = {Publisher Correction: An extracellular network of Arabidopsis leucine-rich repeat receptor kinases.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {E8}, doi = {10.1038/s41586-018-0268-y}, pmid = {29973716}, issn = {1476-4687}, abstract = {In this Letter, an incorrect version of the Supplementary Information file was inadvertently used, which contained several errors. The details of references 59-65 were missing from the end of the Supplementary Discussion section on page 4. In addition, the section 'Text 3. Y2H on ICD interactions' incorrectly referred to 'Extended Data Fig. 4d' instead of 'Extended Data Fig. 3d' on page 3. Finally, the section 'Text 4. Interaction network analysis' incorrectly referred to 'Fig. 1b and Extended Data Fig. 6' instead of 'Fig. 2b and Extended Data Fig. 7' on page 3. These errors have all been corrected in the Supplementary Information.}, } @article {pmid29973715, year = {2018}, author = {Huang, W and Thomas, B and Flynn, RA and Gavzy, SJ and Wu, L and Kim, SV and Hall, JA and Miraldi, ER and Ng, CP and Rigo, F and Meadows, S and Montoya, NR and Herrera, NG and Domingos, AI and Rastinejad, F and Myers, RM and Fuller-Pace, FV and Bonneau, R and Chang, HY and Acuto, O and Littman, DR}, title = {Retraction Note: DDX5 and its associated lncRNA Rmrp modulate TH17 cell effector functions.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {150}, doi = {10.1038/s41586-018-0311-z}, pmid = {29973715}, issn = {1476-4687}, abstract = {Change History: This Article has been retracted; see accompanying Retraction. Corrected online 20 January: In this Article, author Frank Rigo was incorrectly listed with a middle initial; this has been corrected in the online versions of the paper.}, } @article {pmid29973714, year = {2018}, author = {Shalapour, S and Lin, XJ and Bastian, IN and Brain, J and Burt, AD and Aksenov, AA and Vrbanac, AF and Li, W and Perkins, A and Matsutani, T and Zhong, Z and Dhar, D and Navas-Molina, JA and Xu, J and Loomba, R and Downes, M and Yu, RT and Evans, RM and Dorrestein, PC and Knight, R and Benner, C and Anstee, QM and Karin, M}, title = {Author Correction: Inflammation-induced IgA+ cells dismantle anti-liver cancer immunity.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {E1}, doi = {10.1038/s41586-018-0304-y}, pmid = {29973714}, issn = {1476-4687}, abstract = {In this Article, the sentence: "After 7 months of HFD, MUP-uPA mice developed HCC15, which contained numerous (usually 50-100 per tumour) non-recurrent coding mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).", should have read: "After 7 months of HFD, MUP-uPA mice developed HCC15, which contained numerous (usually 50-100 per tumour) non-recurrent mutations in pathways that are mutated in human HCC (Fig. 2d and Extended Data Fig. 6a).". This has been corrected online. In Extended Data Fig. 6a and b, which show the number of point mutations identified per sample and the mutational signatures, all sequence variants (including non-coding mutations) are shown. Fig. 2d also presents all variants compared to human mutations. In the Supplementary Information to this Amendment, we now provide the comparisons of all variants and coding variants to human mutations.}, } @article {pmid29973713, year = {2018}, author = {Naik, S and Larsen, SB and Gomez, NC and Alaverdyan, K and Sendoel, A and Yuan, S and Polak, L and Kulukian, A and Chai, S and Fuchs, E}, title = {Author Correction: Inflammatory memory sensitizes skin epithelial stem cells to tissue damage.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {E2}, doi = {10.1038/s41586-018-0229-5}, pmid = {29973713}, issn = {1476-4687}, abstract = {In Fig. 2g of this Article, a panel was inadvertently duplicated. The 'D30 IMQ' image was a duplicate of the 'D6 Ctrl' image. Fig. 2g has been corrected online to show the correct 'D30 IMQ' image (showing skin inflammation induced by the NALP3 agonist imiquimod, IMQ). The Supplementary Information to this Amendment contains the old, incorrect Fig. 2 for transparency.}, } @article {pmid29973711, year = {2018}, author = {Frigola, J and Sabarinathan, R and Mularoni, L and Muiños, F and Gonzalez-Perez, A and López-Bigas, N}, title = {Author Correction: Reduced mutation rate in exons due to differential mismatch repair.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1196}, doi = {10.1038/s41588-018-0123-y}, pmid = {29973711}, issn = {1546-1718}, abstract = {In the version of this article initially published, the x axis on the fourth plot in Fig. 2e was incorrectly labeled "H3K36me3 exon-to-intron ratio (lower to higher)." The x axis on this plot should read "Genic H3K36me3 coverage bins (higher to lower)".}, } @article {pmid29973680, year = {2018}, author = {Sheppard, SK and Guttman, DS and Fitzgerald, JR}, title = {Population genomics of bacterial host adaptation.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {549-565}, doi = {10.1038/s41576-018-0032-z}, pmid = {29973680}, issn = {1471-0064}, abstract = {Some bacteria can transfer to new host species, and this poses a risk to human health. Indeed, an estimated 60% of all human pathogens have originated from other animal species. Similarly, human-to-animal transitions are recognized as a major threat to sustainable livestock production, and emerging pathogens impose an increasing burden on crop yield and global food security. Recent advances in high-throughput sequencing technologies have enabled comparative genomic analyses of bacterial populations from multiple hosts. Such studies are providing new insights into the evolutionary processes that underpin the establishment of bacteria in new host niches. A better understanding of the genetic and mechanistic basis for bacterial host adaptation may reveal novel targets for controlling infection or inform the design of approaches to limit the emergence of new pathogens.}, } @article {pmid29973274, year = {2018}, author = {Lundgren, SN and Madan, JC and Emond, JA and Morrison, HG and Christensen, BC and Karagas, MR and Hoen, AG}, title = {Maternal diet during pregnancy is related with the infant stool microbiome in a delivery mode-dependent manner.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {109}, pmid = {29973274}, issn = {2049-2618}, support = {R01 LM012723/LM/NLM NIH HHS/United States ; K01 LM011985/LM/NLM NIH HHS/United States ; R01 DE022772/DE/NIDCR NIH HHS/United States ; P01 ES022832/ES/NIEHS NIH HHS/United States ; UG3 OD023275/OD/NIH HHS/United States ; P20 GM104416/GM/NIGMS NIH HHS/United States ; }, mesh = {Adult ; Bacteroides/classification/genetics/*isolation & purification ; Bifidobacterium/classification/genetics/*isolation & purification ; *Cesarean Section ; Clostridium/classification/genetics/*isolation & purification ; Dairy Products ; *Diet ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; RNA, Ribosomal, 16S/genetics ; Seafood ; Streptococcus/classification/genetics/*isolation & purification ; Surveys and Questionnaires ; Young Adult ; }, abstract = {BACKGROUND: The gut microbiome has an important role in infant health and immune development and may be affected by early-life exposures. Maternal diet may influence the infant gut microbiome through vertical transfer of maternal microbes to infants during vaginal delivery and breastfeeding. We aimed to examine the association of maternal diet during pregnancy with the infant gut microbiome 6 weeks post-delivery in mother-infant dyads enrolled in the New Hampshire Birth Cohort Study. Infant stool samples were collected from 145 infants, and maternal prenatal diet was assessed using a food frequency questionnaire. We used targeted sequencing of the 16S rRNA V4-V5 hypervariable region to characterize infant gut microbiota. To account for differences in baseline and trajectories of infant gut microbial profiles, we stratified analyses by delivery mode.

RESULTS: We identified three infant gut microbiome clusters, characterized by increased abundance of Bifidobacterium, Streptococcus and Clostridium, and Bacteroides, respectively, overall and in the vaginally delivered infant stratum. In the analyses stratified to infants born vaginally and adjusted for other potential confounders, maternal fruit intake was associated with infant gut microbial community structure (PERMANOVA, p < 0.05). In multinomial logistic regression analyses, increased fruit intake was associated with an increased odds of belonging to the high Streptococcus/Clostridium group among infants born vaginally (OR (95% CI) = 2.73 (1.36, 5.46)). In infants delivered by Cesarean section, we identified three clusters that differed slightly from vaginally delivered infants, which were characterized by a high abundance of Bifidobacterium, high Clostridium and low Streptococcus and Ruminococcus genera, and high abundance of the family Enterobacteriaceae. Maternal dairy intake was associated with an increased odds of infants belonging to the high Clostridium cluster in infants born by Cesarean section (OR (95% CI) = 2.36 (1.05, 5.30)). Linear models suggested additional associations between maternal diet and infant intestinal microbes in both delivery mode strata.

CONCLUSIONS: Our data indicate that maternal diet influences the infant gut microbiome and that these effects differ by delivery mode.}, } @article {pmid29973269, year = {2018}, author = {Iyasu, A and Ayana Hordofa, M and Zeleke, H and Leshargie, CT}, title = {Level and factors associated with birth preparedness and complication readiness among semi-pastoral pregnant women in southern Ethiopia, 2016.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {442}, pmid = {29973269}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; *Delivery, Obstetric ; Ethiopia ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Middle Aged ; Pregnancy ; Pregnant Women/*psychology ; Prenatal Care ; Young Adult ; }, abstract = {OBJECTIVE: The objective of this study was to determine the level of birth preparedness and complication readiness (BPCR) and associated factors among semi-pastoral pregnant women in southern, Ethiopia.

RESULT: This dataset contains the full data collected from 746 pregnant women. Birth preparedness and complication readiness among women in southern Ethiopia was 27.1%. The main predictors for BRCP were attending formal education (AOR = 4.65, 95% CI 2.45-8.63), husband occupation [merchant (AOR = 3.83, 95% CI 1.52-9.64)], spouse attending formal education (AOR = 3.35, 95% CI (1.83-6.14), ANC visits > 4 times (AOR = 17.78, 95% CI 7.11-44.47). In addition, knowledge of women at least two danger signs during pregnancy, delivery and after delivery (AOR = 3.32, 95% CI 1.64-6.69), (AOR = 3.13, 95% CI 1.58-6.20) and (AOR = 3.75, 95% CI 1.93-7.28) respectively were significantly associated with BPCR. In conclusion, the proportion of BPCR among women in southern Ethiopia was found to be low.}, } @article {pmid29973263, year = {2018}, author = {Islam, F and Roy, N}, title = {Screening, purification and characterization of cellulase from cellulase producing bacteria in molasses.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {445}, pmid = {29973263}, issn = {1756-0500}, mesh = {Aeromonas/enzymology ; Bacillus/enzymology ; Cellulase/*isolation & purification/metabolism ; Cellulose ; Enzyme Stability ; Hydrogen-Ion Concentration ; Molasses/*microbiology ; Paenibacillus/enzymology ; Substrate Specificity ; Temperature ; }, abstract = {OBJECTIVES: This study was conducted to isolate, screening and purification of cellulase from bacteria present in sugar industry waste (molasses) and characterization by morphological and biochemical analysis.

RESULTS: Based on experiments, three bacterial strains produced clear transparent zone into carboxymethyl cellulose (CMC) agar plate were identified as cellulase producing bacteria. Different culture parameters such as pH, temperature, incubation period, substrate concentration and carbon sources were optimized for enzyme production. According to the morphological and biochemical tests, the isolated strains were identified as Paenibacillus sp., Bacillus sp. and Aeromonas sp. The first strain Paenibacillus sp. showed high potentiality for maximum cellulase production (0.9 µmol ml-1 min-1) at pH 7.0 after 24 h of incubation at 40 °C in a medium containing 1.0% CMC. Then Paenibacillus sp. was selected for enzyme purification by ammonium sulfate precipitation, DEAE-cellulose and CM-cellulose column chromatography, respectively. In last step of purification, specific activity, recovery and purification fold were 2655 U/mg, 35.7% and 9.7, respectively. The molecular weight of the purified cellulase was found to be 67 kDa by SDS-PAGE, had an optimal pH and temperature at 7.0 and 40 °C. According to substrate specificity, the purified cellulase had high specificity on CMC substrate which indicated it to be an endo-β-1,4-glucanase.}, } @article {pmid29973255, year = {2018}, author = {Teshale, T and Belay, S and Tadesse, D and Awala, A and Teklay, G}, title = {Prevalence of intestinal helminths and associated factors among school children of Medebay Zana wereda; North Western Tigray, Ethiopia 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {444}, pmid = {29973255}, issn = {1756-0500}, mesh = {Adolescent ; Animals ; Child ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Feces ; Female ; Helminthiasis/*epidemiology ; Helminths ; Humans ; Intestinal Diseases, Parasitic/*epidemiology ; Male ; Prevalence ; Young Adult ; }, abstract = {OBJECTIVE: To assess the prevalence of intestinal helminth infections and associated factors among primary school children of Medebay Zana wereda, a northwestern zone of Tigray, northern Ethiopia from March to April 2017.

RESULT: The prevalence of intestinal helminths was 12.7%. The highest prevalence of intestinal helminth infections was observed in the age group of 11-14 years old and the most prevalent helminths species were Schistosoma mansoni. Mothers' level of education [AOR = 0.27 [0.13-0.58]], place of defecation [AOR = 2.63, 95% CI 1.14-6.02]], hand wash before meals [AOR = 9.0, 95% CI 3.72-21.74]], hand wash after defecation [AOR = 5.77 [1.78-18.63]] and eating unwashed vegetables [AOR = 5.67 [2.19-14.73]] were associated with higher risk of having intestinal helminths detected in stool. In the study area the risk of detecting intestinal helminths in their stool were more associated the improper personal hygiene of the children.}, } @article {pmid29973253, year = {2018}, author = {Le Maréchal, C and Fourour, S and Ballan, V and Rouxel, S and Souillard, R and Chemaly, M}, title = {Detection of Clostridium botulinum group III in environmental samples from farms by real-time PCR using four commercial DNA extraction kits.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {441}, pmid = {29973253}, issn = {1756-0500}, support = {BOTUNET//France AgriMer/ ; }, mesh = {Animals ; Clostridium botulinum/*isolation & purification ; DNA, Bacterial/*analysis ; Environmental Monitoring ; Farms ; Feces ; *Real-Time Polymerase Chain Reaction ; }, abstract = {OBJECTIVES: Few studies have tested DNA extraction methods to optimize the detection of Clostridium botulinum in environmental samples that can be collected during animal botulism outbreaks. In this study, we evaluated four commercial DNA extraction kits for the detection of C. botulinum group III in 82 various environmental samples (9 manure, 53 swabs, 3 insects, 8 water, 1 silage and 8 soil samples) collected in a context of animal botulism outbreaks.

RESULTS: The PowerSoil® kit was the most efficient for almost all matrices (83.6% of the 73 tested samples), except manure for which the NucleoSpin® Soil kit was the most efficient. The NucleoSpin® Soil kit enabled detection in 75.3%, the QIAamp® DNA Mini Kit in 68.5%, and the QIAamp® Fast DNA Stool Mini Kit in 45.2%. However, the NucleoSpin® Soil kit detected C. botulinum in 9 of the 9 manure samples tested, while the PowerSoil® kit found C. botulinum in only two samples, and the other two kits in none of the samples. This study showed that PowerSoil® can be recommended for DNA extraction from environmental samples except for manure, for which the NucleoSpin® Soil kit appeared to be far more appropriate.}, } @article {pmid29973249, year = {2018}, author = {Sumaila, AN and Tabong, PT}, title = {Rational prescribing of antibiotics in children under 5 years with upper respiratory tract infections in Kintampo Municipal Hospital in Brong Ahafo Region of Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {443}, pmid = {29973249}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Child ; Drug Prescriptions ; Ghana ; Hospitals, Municipal ; Humans ; *Practice Patterns, Physicians' ; Respiratory Tract Infections/*drug therapy ; }, abstract = {OBJECTIVE: The aim of the study was to assess the rational use of antibiotics in children with URTIs in the Kintampo Municipal Hospital in Ghana.

RESULTS: A total of 839 medicines were prescribed, 237 were antibiotics. The mean number of medicines prescribed per patient encounter was 3.1. The percentage of patient encounters with antibiotics was 28.2 and 0.4% for injections. The percentage of medicines prescribed by generic was 93.8% and from the essential medicines list was 94.9%. Ninety-two of patients received amoxicillin. Polypharmacy was common as prescriptions with five to six medicines per patient encounter was found. Some prescribers are not following the WHO/INRUD requirement of prescribing medicines in their generic and from the essential medicine list of the country.}, } @article {pmid29973198, year = {2018}, author = {Borowsky, R and Luk, A and He, X and Kim, RS}, title = {Unique sperm haplotypes are associated with phenotypically different sperm subpopulations in Astyanax fish.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {72}, pmid = {29973198}, issn = {1741-7007}, abstract = {BACKGROUND: The phenotypes of sperm are generally believed to be under the control of the diploid genotype of the male producing them rather than their own haploid genotypes, because developing spermatids share cytoplasm through intercellular bridges. This sharing is believed to homogenize their content of gene products. However, not all developing spermatids have identical gene products and estimates are that alleles at numerous gene loci are unequally expressed in sperm. This provides scope for the hypothesis that sperm phenotypes might be influenced by their unique haplotypes. Here we test a key prediction of this hypothesis.

RESULTS: The haploid hypothesis predicts that phenotypically different sperm subpopulations should be genetically distinct. We tested this by genotyping different sperm subpopulations that were generated by exposing sperm to a chemical dye challenge (Hoechst 33342). Dye treatment caused the cells to swell and tend to clump together. The three subpopulations of sperm we distinguished in flow cytometry corresponded to single cells, and clumps of two or three. Cell clumping in the presence of the dye may reflect variation in cell adhesivity. We found that allelic contents differed among the three populations. Importantly, the subpopulations with clumped sperm cells were significantly enriched in allelic combinations that had previously been observed to have significantly lower transmission success.

CONCLUSIONS: We show that at least one sperm phenotype is correlated with its haploid genotype. This supports a broader hypothesis that the haploid genotypes of sperm cells may influence their fitness, with potentially significant implications for the transmission of deleterious alleles or combinations of alleles to their offspring.}, } @article {pmid29973160, year = {2018}, author = {Bartáková, V and Bryja, J and Reichard, M}, title = {Fine-scale genetic structure of the European bitterling at the intersection of three major European watersheds.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {105}, pmid = {29973160}, issn = {1471-2148}, support = {13-05872S//Grantová Agentura České Republiky/International ; P505/12/G112//Grantová Agentura České Republiky/International ; }, mesh = {Animals ; Bayes Theorem ; Carps/*genetics ; DNA, Mitochondrial/genetics ; Europe ; Fresh Water ; Gene Frequency/genetics ; Genetic Variation ; Genetics, Population ; Geography ; Humans ; Microsatellite Repeats/genetics ; Mitochondria/genetics ; North Sea ; *Rivers ; Species Specificity ; }, abstract = {BACKGROUND: Anthropogenic factors can have a major impact on the contemporary distribution of intraspecific genetic diversity. Many freshwater fishes have finely structured and locally adapted populations, but their natural genetic structure can be affected by river engineering schemes across river basins, fish transfers in aquaculture industry and conservation management. The European bitterling (Rhodeus amarus) is a small fish that is a brood parasite of freshwater mussels and is widespread across continental Europe. Its range recently expanded, following sharp declines in the 1970s and 1980s. We investigated its genetic variability and spatial structure at the centre of its distribution at the boundary of three watersheds, testing the role of natural and anthropogenic factors in its genetic structure.

RESULTS: Sequences of mitochondrial cytochrome B (CYTB) revealed that bitterling colonised central Europe from two Ponto-Caspian refugia, which partly defines its contemporary genetic structure. Twelve polymorphic microsatellite loci revealed pronounced interpopulation differentiation, with significant small-scale differentiation within the same river basins. At a large scale, populations from the Baltic Sea watershed (middle Oder and Vistula basins) were distinct from those from the Black Sea watershed (Danube basin), while populations from rivers of the North Sea watershed (Rhine, Elbe) originated from the admixture of both original sources. Notable exceptions demonstrated the potential role of human translocations across watersheds, with the upper River Oder (Baltic watershed) inhabited by fish from the Danube basin (Black Sea watershed) and a population in the southern part of the River Elbe (North Sea watershed) basin possessing a signal of admixture from the Danube basin.

CONCLUSIONS: Hydrography and physical barriers to dispersal are only partly reflected in the genetic structure of the European bitterling at the intersection of three major watersheds in central Europe. Drainage boundaries have been obscured by human-mediated translocations, likely related to common carp, Cyprinus carpio, cultivation and game-fish management. Despite these translocations, populations of bitterling are significantly structured by genetic drift, possibly reinforced by its low dispersal ability. Overall, the impact of anthropogenic factors on the genetic structure of the bitterling populations in central Europe is limited.}, } @article {pmid29973159, year = {2018}, author = {Yamaguchi, T and Higa, N and Okura, N and Matsumoto, A and Hermawan, I and Yamashiro, T and Suzuki, T and Toma, C}, title = {Characterizing interactions of Leptospira interrogans with proximal renal tubule epithelial cells.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {64}, pmid = {29973159}, issn = {1471-2180}, abstract = {BACKGROUND: Leptospira interrogans is a pathogenic, spirochetal bacterium that is responsible for leptospirosis, an emerging worldwide zoonosis. Leptospires colonize the renal proximal tubules and chronically infect the kidney. Live bacteria are excreted into urine, contaminating the environment. While it is well known that leptospires can persist in the kidneys without signs of disease for several months, the interactions of leptospires with the proximal renal epithelial tubule cells that allow the chronic renal colonization have not been elucidated yet. In the present study, we compared the interactions between a virulent, low passage (LP) strain and a cultured-attenuated, high passage (HP) strain with renal proximal tubule epithelial cells (RPTECs) to elucidate the strategies used by Leptospira to colonize the kidney.

RESULTS: Kinetics analysis of kidney colonization in a mouse model of chronic infection performed by quantitative real-time PCR and immunofluorescence, showed that the LP strain reached the kidney by 3 days post infection (pi) and attached to the basal membrane side of the renal epithelial cells. At 10 days pi, some leptospires were attached to the luminal side of the tubular epithelia and the number of colonizing leptospires gradually increased. On the other hand, the HP strain was cleared during hematogenous dissemination and did not colonize the kidney. Transmission electron microscopy analysis of LP-infected kidneys at 25 days pi showed aggregated leptospires and membrane vesicles attached to the epithelial brush border. Leptospiral kidney colonization altered the organization of the RPTEC brush border. An in vitro model of infection using TCMK-1 cells, showed that leptospiral infection induced a host stress response, which is delayed in LP-infected cells.

CONCLUSIONS: After hematogenous dissemination, leptospires create protective and replicative niches in the base membrane and luminal sides of the RPTECs. During the long-term colonization, leptospires attached to the RPTEC brush borders and membrane vesicles might be involved in the formation of a biofilm-like structure in vivo. Our results also suggested that the virulent strain is able to manipulate host cell stress responses to promote renal colonization.}, } @article {pmid29973157, year = {2018}, author = {Ruan, J and Guo, F and Wang, Y and Li, X and Wan, S and Shan, L and Peng, Z}, title = {Transcriptome analysis of alternative splicing in peanut (Arachis hypogaea L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {139}, pmid = {29973157}, issn = {1471-2229}, support = {31470349//National Natural Science Foundation of China/ ; 2014-2017//Shandong Province Germplasm Innovation/ ; 2015DFA31190//International Science & Technology Cooperation Program of China/ ; 2014BAD11B04//the Supporting Plan of National Science and Technology of China/ ; CARS-14//the earmarked fund for Modern Agroindustry Technology Research System/ ; }, abstract = {BACKGROUND: Alternative splicing (AS) represents a mechanism widely used by eukaryotes for the post-transcriptional regulation of genes. The detailed exploration of AS in peanut has not been documented.

RESULTS: The strand-specific RNA-Seq technique was exploited to characterize the distribution of AS in the four samples of peanut (FH1-seed1, FH1-seed2, FH1-root and FH1-leaf). AS was detected as affecting around 37.2% of the full set of multi-exon genes. Some of these genes experienced AS throughout the plant, while in the case of others, the effect was organ-specific. Overall, AS was more frequent in the seed than in either the root or leaf. The predominant form of AS was intron retention, and AS in transcription start site and transcription terminal site were commonly identified in all the four samples. It is interesting that in genes affected by AS, the majority experienced only a single type of event. Not all of the in silico predicted transcripts appeared to be translated, implying that these are either degraded or sequestered away from the translation machinery. With respect to genes involved in fatty acid metabolism, about 61.6% were shown to experience AS.

CONCLUSION: Our report contributes significantly in AS analysis of peanut genes in general, and these results have not been mentioned before. The specific functions of different AS forms need further investigation.}, } @article {pmid29973156, year = {2018}, author = {Pais, M and Yoshida, K and Giannakopoulou, A and Pel, MA and Cano, LM and Oliva, RF and Witek, K and Lindqvist-Kreuze, H and Vleeshouwers, VGAA and Kamoun, S}, title = {Gene expression polymorphism underpins evasion of host immunity in an asexual lineage of the Irish potato famine pathogen.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {93}, pmid = {29973156}, issn = {1471-2148}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Gene Expression Regulation ; Host-Pathogen Interactions/*genetics ; Immune Evasion/*genetics ; Immunity/*genetics ; Phylogeny ; Phytophthora infestans/*genetics/pathogenicity ; Plant Diseases/*immunology/microbiology ; *Polymorphism, Genetic ; Solanum tuberosum/*immunology/*microbiology ; Virulence ; }, abstract = {BACKGROUND: Outbreaks caused by asexual lineages of fungal and oomycete pathogens are a continuing threat to crops, wild animals and natural ecosystems (Fisher MC, Henk DA, Briggs CJ, Brownstein JS, Madoff LC, McCraw SL, Gurr SJ, Nature 484:186-194, 2012; Kupferschmidt K, Science 337:636-638, 2012). However, the mechanisms underlying genome evolution and phenotypic plasticity in asexual eukaryotic microbes remain poorly understood (Seidl MF, Thomma BP, BioEssays 36:335-345, 2014). Ever since the 19th century Irish famine, the oomycete Phytophthora infestans has caused recurrent outbreaks on potato and tomato crops that have been primarily caused by the successive rise and migration of pandemic asexual lineages (Goodwin SB, Cohen BA, Fry WE, Proc Natl Acad Sci USA 91:11591-11595, 1994; Yoshida K, Burbano HA, Krause J, Thines M, Weigel D, Kamoun S, PLoS Pathog 10:e1004028, 2014; Yoshida K, Schuenemann VJ, Cano LM, Pais M, Mishra B, Sharma R, Lanz C, Martin FN, Kamoun S, Krause J, et al. eLife 2:e00731, 2013; Cooke DEL, Cano LM, Raffaele S, Bain RA, Cooke LR, Etherington GJ, Deahl KL, Farrer RA, Gilroy EM, Goss EM, et al. PLoS Pathog 8:e1002940, 2012). However, the dynamics of genome evolution within these clonal lineages have not been determined. The objective of this study was to use a comparative genomics and transcriptomics approach to determine the molecular mechanisms that underpin phenotypic variation within a clonal lineage of P. infestans.

RESULTS: Here, we reveal patterns of genomic and gene expression variation within a P. infestans asexual lineage by comparing strains belonging to the South American EC-1 clone that has dominated Andean populations since the 1990s (Yoshida K, Burbano HA, Krause J, Thines M, Weigel D, Kamoun S, PLoS Pathog 10e1004028, 2014; Yoshida K, Schuenemann VJ, Cano LM, Pais M, Mishra B, Sharma R, Lanz C, Martin FN, Kamoun S, Krause J, et al. eLife 2:e00731, 2013; Delgado RA, Monteros-Altamirano AR, Li Y, Visser RGF, van der Lee TAJ, Vosman B, Plant Pathol 62:1081-1088, 2013; Forbes GA, Escobar XC, Ayala CC, Revelo J, Ordonez ME, Fry BA, Doucett K, Fry WE, Phytopathology 87:375-380, 1997; Oyarzun PJ, Pozo A, Ordonez ME, Doucett K, Forbes GA, Phytopathology 88:265-271, 1998). We detected numerous examples of structural variation, nucleotide polymorphisms and loss of heterozygosity within the EC-1 clone. Remarkably, 17 genes are not expressed in one of the two EC-1 isolates despite apparent absence of sequence polymorphisms. Among these, silencing of an effector gene was associated with evasion of disease resistance conferred by a potato immune receptor.

CONCLUSIONS: Our findings highlight the molecular changes underpinning the exceptional genetic and phenotypic plasticity associated with host adaptation in a pandemic clonal lineage of a eukaryotic plant pathogen. We observed that the asexual P. infestans lineage EC-1 can exhibit phenotypic plasticity in the absence of apparent genetic mutations resulting in virulence on a potato carrying the Rpi-vnt1.1 gene. Such variant alleles may be epialleles that arose through epigenetic changes in the underlying genes.}, } @article {pmid29973152, year = {2018}, author = {Vanhove, MPM and Briscoe, AG and Jorissen, MWP and Littlewood, DTJ and Huyse, T}, title = {The first next-generation sequencing approach to the mitochondrial phylogeny of African monogenean parasites (Platyhelminthes: Gyrodactylidae and Dactylogyridae).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {520}, pmid = {29973152}, issn = {1471-2164}, support = {BR/132/PI/TILAPIA//Federaal Wetenschapsbeleid/ ; GB-TAF-2984//SYNTHESYS/ ; GB-TAF-4940//SYNTHESYS/ ; ZRDC2014MP084//Vlaamse Interuniversitaire Raad/ ; P505/12/G112 (ECIP)//Grantová Agentura České Republiky/ ; K220314N//Fonds Wetenschappelijk Onderzoek/ ; Mbisa Congo project//Belgian Development Cooperation/ ; BOF Reserve Fellowship//Universiteit Hasselt/ ; }, mesh = {Animals ; Cichlids/*parasitology ; DNA, Protozoan/chemistry/isolation & purification/metabolism ; Gene Order ; Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/classification/*genetics ; Phylogeny ; Platyhelminths/*genetics ; Protozoan Proteins/classification/genetics ; RNA, Ribosomal/classification/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Monogenean flatworms are the main ectoparasites of fishes. Representatives of the species-rich families Gyrodactylidae and Dactylogyridae, especially those infecting cichlid fishes and clariid catfishes, are important parasites in African aquaculture, even more so due to the massive anthropogenic translocation of their hosts worldwide. Several questions on their evolution, such as the phylogenetic position of Macrogyrodactylus and the highly speciose Gyrodactylus, remain unresolved with available molecular markers. Also, diagnostics and population-level research would benefit from the development of higher-resolution genetic markers. We aim to offer genetic resources for work on African monogeneans by providing mitogenomic data of four species (two belonging to Gyrodactylidae, two to Dactylogyridae), and analysing their gene sequences and gene order from a phylogenetic perspective.

RESULTS: Using Illumina technology, the first four mitochondrial genomes of African monogeneans were assembled and annotated for the cichlid parasites Gyrodactylus nyanzae, Cichlidogyrus halli, Cichlidogyrus mbirizei (near-complete mitogenome) and the catfish parasite Macrogyrodactylus karibae (near-complete mitogenome). Complete nuclear ribosomal operons were also retrieved, as molecular vouchers. The start codon TTG is new for Gyrodactylus and for Dactylogyridae, as is the incomplete stop codon TA for Dactylogyridae. Especially the nad2 gene is promising for primer development. Gene order was identical for protein-coding genes and differed between the African representatives of these families only in a tRNA gene transposition. A mitochondrial phylogeny based on an alignment of nearly 12,500 bp including 12 protein-coding and two ribosomal RNA genes confirms that the Neotropical oviparous Aglaiogyrodactylus forficulatus takes a sister group position with respect to the other gyrodactylids, instead of the supposedly 'primitive' African Macrogyrodactylus. Inclusion of the African Gyrodactylus nyanzae confirms the paraphyly of Gyrodactylus. The position of the African dactylogyrid Cichlidogyrus is unresolved, although gene order suggests it is closely related to marine ancyrocephalines.

CONCLUSIONS: The amount of mitogenomic data available for gyrodactylids and dactylogyrids is increased by roughly one-third. Our study underscores the potential of mitochondrial genes and gene order in flatworm phylogenetics, and of next-generation sequencing for marker development for these non-model helminths for which few primers are available.}, } @article {pmid29973148, year = {2018}, author = {Amara, A and Takano, E and Breitling, R}, title = {Development and validation of an updated computational model of Streptomyces coelicolor primary and secondary metabolism.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {519}, pmid = {29973148}, issn = {1471-2164}, support = {BB/M017702/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/metabolism ; Bacterial Proteins/metabolism ; Biomass ; Gene Expression Regulation, Bacterial ; Metabolic Engineering ; *Models, Biological ; Proteomics ; Streptomyces coelicolor/genetics/growth & development/*metabolism ; }, abstract = {BACKGROUND: Streptomyces species produce a vast diversity of secondary metabolites of clinical and biotechnological importance, in particular antibiotics. Recent developments in metabolic engineering, synthetic and systems biology have opened new opportunities to exploit Streptomyces secondary metabolism, but achieving industry-level production without time-consuming optimization has remained challenging. Genome-scale metabolic modelling has been shown to be a powerful tool to guide metabolic engineering strategies for accelerated strain optimization, and several generations of models of Streptomyces metabolism have been developed for this purpose.

RESULTS: Here, we present the most recent update of a genome-scale stoichiometric constraint-based model of the metabolism of Streptomyces coelicolor, the major model organism for the production of antibiotics in the genus. We show that the updated model enables better metabolic flux and biomass predictions and facilitates the integrative analysis of multi-omics data such as transcriptomics, proteomics and metabolomics.

CONCLUSIONS: The updated model presented here provides an enhanced basis for the next generation of metabolic engineering attempts in Streptomyces.}, } @article {pmid29973141, year = {2018}, author = {Xiang, R and Hayes, BJ and Vander Jagt, CJ and MacLeod, IM and Khansefid, M and Bowman, PJ and Yuan, Z and Prowse-Wilkins, CP and Reich, CM and Mason, BA and Garner, JB and Marett, LC and Chen, Y and Bolormaa, S and Daetwyler, HD and Chamberlain, AJ and Goddard, ME}, title = {Genome variants associated with RNA splicing variations in bovine are extensively shared between tissues.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {521}, pmid = {29973141}, issn = {1471-2164}, support = {na//DairyBio/ ; DP160101056//Australian Research Council/ ; }, mesh = {Animals ; Blood Cells/metabolism ; Caseins/genetics ; Cattle ; Exons ; Female ; *Genetic Variation ; Liver/metabolism ; Mammary Glands, Animal/metabolism ; Muscles/metabolism ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; *RNA Splicing ; Transcriptome ; }, abstract = {BACKGROUND: Mammalian phenotypes are shaped by numerous genome variants, many of which may regulate gene transcription or RNA splicing. To identify variants with regulatory functions in cattle, an important economic and model species, we used sequence variants to map a type of expression quantitative trait loci (expression QTLs) that are associated with variations in the RNA splicing, i.e., sQTLs. To further the understanding of regulatory variants, sQTLs were compare with other two types of expression QTLs, 1) variants associated with variations in gene expression, i.e., geQTLs and 2) variants associated with variations in exon expression, i.e., eeQTLs, in different tissues.

RESULTS: Using whole genome and RNA sequence data from four tissues of over 200 cattle, sQTLs identified using exon inclusion ratios were verified by matching their effects on adjacent intron excision ratios. sQTLs contained the highest percentage of variants that are within the intronic region of genes and contained the lowest percentage of variants that are within intergenic regions, compared to eeQTLs and geQTLs. Many geQTLs and sQTLs are also detected as eeQTLs. Many expression QTLs, including sQTLs, were significant in all four tissues and had a similar effect in each tissue. To verify such expression QTL sharing between tissues, variants surrounding (±1 Mb) the exon or gene were used to build local genomic relationship matrices (LGRM) and estimated genetic correlations between tissues. For many exons, the splicing and expression level was determined by the same cis additive genetic variance in different tissues. Thus, an effective but simple-to-implement meta-analysis combining information from three tissues is introduced to increase power to detect and validate sQTLs. sQTLs and eeQTLs together were more enriched for variants associated with cattle complex traits, compared to geQTLs. Several putative causal mutations were identified, including an sQTL at Chr6:87392580 within the 5th exon of kappa casein (CSN3) associated with milk production traits.

CONCLUSIONS: Using novel analytical approaches, we report the first identification of numerous bovine sQTLs which are extensively shared between multiple tissue types. The significant overlaps between bovine sQTLs and complex traits QTL highlight the contribution of regulatory mutations to phenotypic variations.}, } @article {pmid29973137, year = {2018}, author = {Du, L and Zhao, X and Liang, X and Gao, X and Liu, Y and Wang, G}, title = {Identification of candidate chemosensory genes in Mythimna separata by transcriptomic analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {518}, pmid = {29973137}, issn = {1471-2164}, support = {2017YFD0200400//National Key R&D Program of China/ ; 31725023//National Natural Science Foundation of China/ ; 31621064//National Natural Science Foundation of China/ ; 31672095//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Arthropod Antennae/metabolism ; Diptera/*genetics ; Female ; *Gene Expression Profiling ; Insect Proteins/classification/genetics ; Male ; Membrane Proteins/classification/genetics ; Nerve Tissue Proteins/classification/genetics ; Phylogeny ; RNA/chemistry/isolation & purification/metabolism ; Receptors, Ionotropic Glutamate/classification/genetics ; Receptors, Odorant/classification/genetics ; Sequence Analysis, RNA ; Transcriptome ; }, abstract = {BACKGROUND: The oriental armyworm, Mythimna separata, is an economically important and common Lepidopteran pest of cereal crops. Chemoreception plays a key role in insect life, such as foraging, oviposition site selection, and mating partners. To better understand the chemosensory mechanisms in M. separata, transcriptomic analysis of antennae, labial palps, and proboscises were conducted using next-generation sequencing technology to identify members of the major chemosensory related genes.

RESULTS: In this study, 62 putative odorant receptors (OR), 20 ionotropic receptors (IR), 16 gustatory receptors (GR), 38 odorant binding proteins (OBP), 26 chemosensory proteins (CSP), and 2 sensory neuron membrane proteins (SNMP) were identified in M. separata by bioinformatics analysis. Phylogenetic analysis of these candidate proteins was performed. Differentially expressed genes (DEGs) analysis was used to determine the expressions of all candidate chemosensory genes and then the expression profiles of the three families of receptor genes were confirmed by real-time quantitative RT-PCR (qPCR).

CONCLUSIONS: The important genes for chemoreception have now been identified in M. separata. This study will provide valuable information for further functional studies of chemoreception mechanisms in this important agricultural pest.}, } @article {pmid29973136, year = {2018}, author = {Roumane, A and Berthenet, K and El Fassi, C and Ichim, G}, title = {Caspase-independent cell death does not elicit a proliferative response in melanoma cancer cells.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {11}, pmid = {29973136}, issn = {1471-2121}, support = {aALTF 772-2015//EMBO/International ; 20171206348//ARC Jeune Chercheur/International ; }, mesh = {*Apoptosis ; Caspases/*metabolism ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Humans ; Melanoma/*enzymology/*pathology ; Models, Biological ; }, abstract = {BACKGROUND: Apoptosis, the most well-known type of programmed cell death, can induce in a paracrine manner a proliferative response in neighboring surviving cells called apoptosis-induced proliferation (AiP). While having obvious benefits when triggered in developmental processes, AiP is a serious obstacle in cancer therapy, where apoptosis is frequently induced by chemotherapy. Therefore, in this study, we evaluated the capacity of an alternative type of cell death, called caspase-independent cell death, to promote proliferation.

RESULTS: Using a novel in vitro isogenic cellular model to trigger either apoptosis or caspase-independent cell death, we found that the later has no obvious compensatory proliferation effects on neighboring cells.

CONCLUSIONS: This study enforces the idea that alternative types of cell death such as caspase-independent cell death could be considered to replace apoptosis in the context of cancer treatment.}, } @article {pmid29973133, year = {2018}, author = {Shapiro, M and Meier, S and MacCarthy, T}, title = {Correction to: The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {256}, pmid = {29973133}, issn = {1471-2105}, support = {R01 GM111741/GM/NIGMS NIH HHS/United States ; }, abstract = {Following publication of the original article [1], the authors reported that Figs. 1 and 3 were interchanged. The original article has been corrected.}, } @article {pmid29972584, year = {2018}, author = {English, HM}, title = {Digest: Pursue or ambush? Phenotypic disparity in the carnivore forelimb.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13542}, pmid = {29972584}, issn = {1558-5646}, abstract = {The way an animal moves reveals key aspects of its ecology. Carnivore forelimbs are adapted to their predation style, and the structure of the elbow joint can indicate hunting strategy. In this issue, Figueirido (2018) investigates phenotypic disparity, or morphological variation, in domestic dog breeds, the canid family, and the carnivore order using the elbow joint as an indicator of movement and predatory behavior.}, } @article {pmid29972583, year = {2018}, author = {Augstenová, B and Johnson Pokorná, M and Altmanová, M and Frynta, D and Rovatsos, M and Kratochvíl, L}, title = {ZW, XY, and yet ZW: Sex chromosome evolution in snakes even more complicated.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13543}, pmid = {29972583}, issn = {1558-5646}, abstract = {Snakes are historically important in the formulation of several central concepts on the evolution of sex chromosomes. For over 50 years, it was believed that all snakes shared the same ZZ/ZW sex chromosomes, which are homomorphic and poorly differentiated in "basal" snakes such as pythons and boas, while heteromorphic and well differentiated in "advanced" (caenophidian) snakes. Recent molecular studies revealed that differentiated sex chromosomes are indeed shared among all families of caenophidian snakes, but that boas and pythons evolved likely independently male heterogamety (XX/XY sex chromosomes). The historical report of heteromorphic ZZ/ZW sex chromosomes in a boid snake was previously regarded as ambiguous. In the current study, we document heteromorphic ZZ/ZW sex chromosomes in a boid snake. A comparative approach suggests that these heteromorphic sex chromosomes evolved very recently and that they are poorly differentiated at the sequence level. Interestingly, two snake lineages with confirmed male heterogamety possess homomorphic sex chromosomes, but heteromorphic sex chromosomes are present in both snake lineages with female heterogamety. We point out that this phenomenon is more common across squamates. The presence of female heterogamety in non-caenophidian snakes indicates that the evolution of sex chromosomes in this lineage is much more complex than previously thought, making snakes an even better model system for the evolution of sex chromosomes.}, } @article {pmid29972241, year = {2018}, author = {Start, D and Bonner, C and Weis, AE and Gilbert, B}, title = {Consumer-resource interactions along urbanization gradients drive natural selection.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1863-1873}, doi = {10.1111/evo.13544}, pmid = {29972241}, issn = {1558-5646}, support = {2016-05621//NSERC Discovery Grant/ ; }, abstract = {Urbanization is an important component of global change. Urbanization affects species interactions, but the evolutionary implications are rarely studied. We investigate the evolutionary consequences of a common pattern: the loss of high trophic-level species in urban areas. Using a gall-forming fly, Eurosta solidaginis, and its natural enemies that select for opposite gall sizes, we test for patterns of enemy loss, selection, and local adaptation along five urbanization gradients. Eurosta declined in urban areas, as did predation by birds, which preferentially consume gallmakers that induce large galls. These declines were linked to changes in habitat availability, namely reduced forest cover in urban areas. Conversely, a parasitoid that attacks gallmakers that induce small galls was unaffected by urbanization. Changes in patterns of attack by birds and parasitoids resulted in stronger directional selection, but loss of stabilizing selection in urban areas, a pattern which we suggest may be general. Despite divergent selective regimes, gall size did not very systematically with urbanization, suggesting but not conclusively demonstrating that environmental differences, gene flow, or drift, may have prevented the adaptive divergence of phenotypes. We argue that the evolutionary effects of urbanization will have predictable consequences for patterns of species interactions and natural selection.}, } @article {pmid29972238, year = {2018}, author = {Ashman, LG and Bragg, JG and Doughty, P and Hutchinson, MN and Bank, S and Matzke, NJ and Oliver, P and Moritz, C}, title = {Diversification across biomes in a continental lizard radiation.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13541}, pmid = {29972238}, issn = {1558-5646}, abstract = {Ecological opportunity is a powerful driver of evolutionary diversification, and predicts rapid lineage and phenotypic diversification following colonization of competitor-free habitats. Alternatively, topographic or environmental heterogeneity could be key to generating and sustaining diversity. We explore these hypotheses in a widespread lineage of Australian lizards: the Gehyra variegata group. This clade occurs across two biomes: the Australian monsoonal tropics (AMT), where it overlaps a separate, larger bodied clade of Gehyra and is largely restricted to rocks; and in the larger Australian arid zone (AAZ) where it has no congeners and occupies trees and rocks. New phylogenomic data and coalescent analyses of AAZ taxa resolve lineages and their relationships and reveal high diversity in the western AAZ (Pilbara region). The AMT and AAZ radiations represent separate radiations with no difference in speciation rates. Most taxa occur on rocks, with small geographic ranges relative to widespread generalist taxa across the vast central AAZ. Rock-dwelling and generalist taxa differ morphologically, but only the lineage-poor central AAZ taxa have accelerated evolution. This accords with increasing evidence that lineage and morphological diversity are poorly correlated, and suggests environmental heterogeneity and refugial dynamics have been more important than ecological release in elevating lineage diversity.}, } @article {pmid29971921, year = {2018}, author = {Lachnit, T and Dafforn, KA and Johnston, EL and Steinberg, P}, title = {Contrasting distributions of bacteriophages and eukaryotic viruses from contaminated coastal sediments.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14340}, pmid = {29971921}, issn = {1462-2920}, support = {LP130100364//Australian Research Council/ ; }, abstract = {Viruses are ubiquitous, abundant and play an important role in all ecosystems. Here, we advance understanding of coastal sediment viruses by exploring links in the composition and abundance of sediment viromes to environmental stressors and sediment bacterial communities. We collected sediment from contaminated and reference sites in Sydney Harbour and used metagenomics to analyse viral community composition. The proportion of phages at contaminated sites was significantly greater than phages at reference sites, whereas eukaryotic viruses were relatively more abundant at reference sites. We observed shifts in viral and bacterial composition between contaminated and reference sites of a similar magnitude. Models based on sediment characteristics revealed that total organic carbon in the sediments explained most of the environmental stress-related variation in the viral dataset. Our results suggest that the presence of anthropogenic contaminants in coastal sediments could be influencing viral community composition with potential consequences for associated hosts and the environment.}, } @article {pmid29971905, year = {2018}, author = {Fuchs, AJ and Bell, RB and Lazagabaster, I and Zamora, AJ}, title = {The 87th annual meeting of the American Association of Physical Anthropologists in Austin, Texas.}, journal = {Evolutionary anthropology}, volume = {27}, number = {3}, pages = {98-101}, doi = {10.1002/evan.21592}, pmid = {29971905}, issn = {1520-6505}, } @article {pmid29971904, year = {2018}, author = {Port, M and Schülke, O and Ostner, J}, title = {Reproductive tolerance in male primates: Old paradigms and new evidence.}, journal = {Evolutionary anthropology}, volume = {27}, number = {3}, pages = {107-120}, doi = {10.1002/evan.21586}, pmid = {29971904}, issn = {1520-6505}, mesh = {Animals ; Anthropology, Physical ; Biological Evolution ; Female ; Hominidae/*physiology ; Humans ; Male ; Papio/*physiology ; Reproductive Behavior/physiology ; Sexual Behavior, Animal/*physiology ; }, abstract = {Within social groups of primates, males commonly compete over reproduction, but they may also rely on cooperation with other males. Theory suggests that it may be adaptive for male primates to tolerate some reproduction by other males if reproductive tolerance fosters cooperation, particularly that dominant males yield so-called reproductive concessions to subordinates to entice their cooperation. We review four recent studies that claimed to have found evidence for reproductive concessions or similar forms of reproductive tolerance. However, upon critical reevaluation of their results, no study provides conclusive support for reproductive concessions as predicted by theoretical models. Yet two studies demonstrated a form of reproductive tolerance that cannot be explained by any of the existing models, and that seems to have evolved only in multi-male, multi-female societies with diverse strategic options for males. Our article provides guidance how to study this form of reproductive tolerance in the absence of a unifying model.}, } @article {pmid29971903, year = {2018}, author = {Hawkins, NJ and Bass, C and Dixon, A and Neve, P}, title = {The evolutionary origins of pesticide resistance.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12440}, pmid = {29971903}, issn = {1469-185X}, abstract = {Durable crop protection is an essential component of current and future food security. However, the effectiveness of pesticides is threatened by the evolution of resistant pathogens, weeds and insect pests. Pesticides are mostly novel synthetic compounds, and yet target species are often able to evolve resistance soon after a new compound is introduced. Therefore, pesticide resistance provides an interesting case of rapid evolution under strong selective pressures, which can be used to address fundamental questions concerning the evolutionary origins of adaptations to novel conditions. We ask: (i) whether this adaptive potential originates mainly from de novo mutations or from standing variation; (ii) which pre-existing traits could form the basis of resistance adaptations; and (iii) whether recurrence of resistance mechanisms among species results from interbreeding and horizontal gene transfer or from independent parallel evolution. We compare and contrast the three major pesticide groups: insecticides, herbicides and fungicides. Whilst resistance to these three agrochemical classes is to some extent united by the common evolutionary forces at play, there are also important differences. Fungicide resistance appears to evolve, in most cases, by de novo point mutations in the target-site encoding genes; herbicide resistance often evolves through selection of polygenic metabolic resistance from standing variation; and insecticide resistance evolves through a combination of standing variation and de novo mutations in the target site or major metabolic resistance genes. This has practical implications for resistance risk assessment and management, and lessons learnt from pesticide resistance should be applied in the deployment of novel, non-chemical pest-control methods.}, } @article {pmid29971901, year = {2018}, author = {Marzocchi, U and Bonaglia, S and van de Velde, S and Hall, POJ and Schramm, A and Risgaard-Petersen, N and Meysman, FJR}, title = {Transient bottom water oxygenation creates a niche for cable bacteria in long-term anoxic sediments of the Eastern Gotland Basin.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3031-3041}, doi = {10.1111/1462-2920.14349}, pmid = {29971901}, issn = {1462-2920}, support = {DNRF104//Danmarks Grundforskningsfond/ ; 306933//FP7 Ideas: European Research Council/ ; 656385//H2020 Marie Sklodowska-Curie Actions/ ; Aspirant PhD fellowshipG031416N//Research Foundation Flanders/ ; G031416N//Research Foundation Flanders/ ; //Vetenskapsrådet/ ; //Swedish Research Council/ ; //European Research Council under the European Union's Seventh Framework Programme/ ; //Danish National Research Foundation/ ; //European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie/ ; }, abstract = {Cable bacteria have been reported in sediments from marine and freshwater locations, but the environmental factors that regulate their growth in natural settings are not well understood. Most prominently, the physiological limit of cable bacteria in terms of oxygen availability remains poorly constrained. In this study, we investigated the presence, activity and diversity of cable bacteria in relation to a natural gradient in bottom water oxygenation in a depth transect of the Eastern Gotland Basin (Baltic Sea). Cable bacteria were identified by FISH at the oxic and transiently oxic sites, but not at the permanently anoxic site. Three species of the candidate genus Electrothrix, i.e. marina, aarhusiensis and communis were found coexisting within one site. The highest filament density (33 m cm-2) was associated with a 6.3 mm wide zone depleted in both oxygen and free sulphide, and the presence of an electric field resulting from the electrogenic sulphur oxidizing metabolism of cable bacteria. However, the measured filament densities and metabolic activities remained low overall, suggesting a limited impact of cable bacteria at the basin level. The observed bottom water oxygen levels (< 5 μM) are the lowest so far reported for cable bacteria, thus expanding their known environmental distribution.}, } @article {pmid29971900, year = {2018}, author = {Truitt, AM and Kapun, M and Kaur, R and Miller, WJ}, title = {Wolbachia modifies thermal preference in Drosophila melanogaster.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14347}, pmid = {29971900}, issn = {1462-2920}, support = {0948041//National Science Foundation/ ; P28255-B22//Austrian Science Fund/ ; }, abstract = {Environmental variation can have profound and direct effects on fitness, fecundity, and host-symbiont interactions. Replication rates of microbes within arthropod hosts, for example, are correlated with incubation temperature but less is known about the influence of host-symbiont dynamics on environmental preference. Hence, we conducted thermal preference (Tp) assays and tested if infection status and genetic variation in endosymbiont bacterium Wolbachia affected temperature choice of Drosophila melanogaster. We demonstrate that isogenic flies infected with Wolbachia preferred lower temperatures compared with uninfected Drosophila. Moreover, Tp varied with respect to three investigated Wolbachia variants (wMel, wMelCS, and wMelPop). While uninfected individuals preferred 24.4°C, we found significant shifts of -1.2°C in wMel- and -4°C in flies infected either with wMelCS or wMelPop. We, therefore, postulate that Wolbachia-associated Tp variation within a host species might represent a behavioural accommodation to host-symbiont interactions and trigger behavioural self-medication and bacterial titre regulation by the host.}, } @article {pmid29971895, year = {2018}, author = {Müller, O and Bang-Andreasen, T and White, RA and Elberling, B and Taş, N and Kneafsey, T and Jansson, JK and Øvreås, L}, title = {Disentangling the complexity of permafrost soil by using high resolution profiling of microbial community composition, key functions and respiration rates.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4328-4342}, doi = {10.1111/1462-2920.14348}, pmid = {29971895}, issn = {1462-2920}, support = {DE-AC05-76LO1803NGEE-Arctic//U.S. Department of Energy (DOE)/ ; AC05-76LO1803//Pacific Northwest National Laboratory/ ; DE-AC02-05CH11231//Lawrence Berkeley National Laboratory/ ; DNRF100//Danish National Research Foundation/ ; //Fulbright foundation/ ; //Norwegian Research Council/ ; }, abstract = {Thawing permafrost can stimulate microbial activity, leading to faster decomposition of formerly preserved organic matter and CO2 release. Detailed knowledge about the vertical distribution of the responsible microbial community that is changing with increasing soil depth is limited. In this study, we determined the microbial community composition from cores sampled in a high Arctic heath at Svalbard, Norway; spanning from the active layer (AL) into the permafrost layer (PL). A special aim has been on identifying a layer of recently thawed soil, the transition zone (TZ), which might provide new insights into the fate of thawing permafrost. A unique sampling strategy allowed us to observe a diverse and gradually shifting microbial community in the AL, a Bacteroidetes dominated community in the TZ and throughout the PL, a community strongly dominated by a single Actinobacteria family (Intrasporangiaceae). The contrasting abundances of these two taxa caused a community difference of about 60%, just within 3 cm from TZ to PL. We incubated subsamples at about 5°C and measured highest CO2 production rates under aerobic incubations, yet contrasting for five different layers and correlating to the microbial community composition. This high resolution strategy provides new insights on how microbial communities are structured in permafrost and a better understanding of how they respond to thaw.}, } @article {pmid29970912, year = {2018}, author = {Nordling, L}, title = {Europe's biggest research fund cracks down on 'ethics dumping'.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {17-18}, doi = {10.1038/d41586-018-05616-w}, pmid = {29970912}, issn = {1476-4687}, mesh = {Biomedical Research/*ethics/*legislation & jurisprudence ; *Developing Countries ; *Ethics, Research ; Europe ; European Union/*economics ; Human Experimentation/*ethics/*legislation & jurisprudence ; Humans ; Kenya ; Patient Safety/legislation & jurisprudence ; Vulnerable Populations/*legislation & jurisprudence ; }, } @article {pmid29970911, year = {2018}, author = {Thompson, M}, title = {Ded-Mek.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {146}, doi = {10.1038/d41586-018-05590-3}, pmid = {29970911}, issn = {1476-4687}, } @article {pmid29970496, year = {2018}, author = {Battersby, S}, title = {News Feature: The carbon detectives.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6873-6877}, doi = {10.1073/pnas.1808901115}, pmid = {29970496}, issn = {1091-6490}, } @article {pmid29970425, year = {2018}, author = {Giresse, P and Maley, J and Doumenge, C and Philippon, N and Mahé, G and Chepstow-Lusty, A and Aleman, J and Lokonda, M and Elenga, H}, title = {Paleoclimatic changes are the most probable causes of the rainforest crises 2,600 y ago in Central Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6672-E6673}, pmid = {29970425}, issn = {1091-6490}, mesh = {Africa, Central ; *Rainforest ; }, } @article {pmid29970424, year = {2018}, author = {Garcin, Y and Deschamps, P and Ménot, G and de Saulieu, G and Schefuß, E and Sebag, D and Dupont, LM and Oslisly, R and Brademann, B and Mbusnum, KG and Onana, JM and Ako, AA and Epp, LS and Tjallingii, R and Strecker, MR and Brauer, A and Sachse, D}, title = {Reply to Giresse et al.: No evidence for climate variability during the late Holocene rainforest crisis in Western Central Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6674-E6675}, pmid = {29970424}, issn = {1091-6490}, mesh = {Africa, Central ; Africa, Western ; *Climate ; *Rainforest ; }, } @article {pmid29970423, year = {2018}, author = {Gorfman, S and Bokov, AA and Davtyan, A and Reiser, M and Xie, Y and Ye, ZG and Zozulya, AV and Sprung, M and Pietsch, U and Gutt, C}, title = {Ferroelectric domain wall dynamics characterized with X-ray photon correlation spectroscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6680-E6689}, pmid = {29970423}, issn = {1091-6490}, abstract = {Technologically important properties of ferroic materials are determined by their intricate response to external stimuli. This response is driven by distortions of the crystal structure and/or by domain wall motion. Experimental separation of these two mechanisms is a challenging problem which has not been solved so far. Here, we apply X-ray photon correlation spectroscopy (XPCS) to extract the contribution of domain wall dynamics to the overall response. Furthermore, we show how to distinguish the dynamics related to the passing of domain walls through the periodic (Peierls) potential of the crystal lattice and through the random potential caused by lattice defects (pinning centers). The approach involves the statistical analysis of correlations between X-ray speckle patterns produced by the interference of coherent synchrotron X-rays scattered from different nanosize volumes of the crystal and identification of Poisson-type contribution to the statistics. We find such a contribution in the thermally driven response of the monoclinic phase of a ferroelectric PbZr0.55Ti0.45O3 crystal and calculate the number of domain wall jumps in the studied microvolume.}, } @article {pmid29970422, year = {2018}, author = {Latychevskaia, T and Woods, CR and Wang, YB and Holwill, M and Prestat, E and Haigh, SJ and Novoselov, KS}, title = {Convergent beam electron holography for analysis of van der Waals heterostructures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7473-7478}, pmid = {29970422}, issn = {1091-6490}, abstract = {The van der Waals heterostructures, which explore the synergetic properties of 2D materials when assembled into 3D stacks, have already brought to life a number of exciting phenomena and electronic devices. Still, the interaction between the layers in such assembly, possible surface reconstruction, and intrinsic and extrinsic defects are very difficult to characterize by any method, because of the single-atomic nature of the crystals involved. Here we present a convergent beam electron holographic technique which allows imaging of the stacking order in such heterostructures. Based on the interference of electron waves scattered on different crystals in the stack, this approach allows one to reconstruct the relative rotation, stretching, and out-of-plane corrugation of the layers with atomic precision. Being holographic in nature, our approach allows extraction of quantitative information about the 3D structure of the typical defects from a single image covering thousands of square nanometers. Furthermore, qualitative information about the defects in the stack can be extracted from the convergent diffraction patterns even without reconstruction, simply by comparing the patterns in different diffraction spots. We expect that convergent beam electron holography will be widely used to study the properties of van der Waals heterostructures.}, } @article {pmid29970421, year = {2018}, author = {Gregory, BD}, title = {Shedding some blue light on alternative promoter usage in plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7654-7656}, pmid = {29970421}, issn = {1091-6490}, mesh = {*Light ; Plants ; *Promoter Regions, Genetic ; }, } @article {pmid29970420, year = {2018}, author = {Dodd, PM and Damasceno, PF and Glotzer, SC}, title = {Universal folding pathways of polyhedron nets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6690-E6696}, pmid = {29970420}, issn = {1091-6490}, abstract = {Low-dimensional objects such as molecular strands, ladders, and sheets have intrinsic features that affect their propensity to fold into 3D objects. Understanding this relationship remains a challenge for de novo design of functional structures. Using molecular dynamics simulations, we investigate the refolding of the 24 possible 2D unfoldings ("nets") of the three simplest Platonic shapes and demonstrate that attributes of a net's topology-net compactness and leaves on the cutting graph-correlate with thermodynamic folding propensity. To explain these correlations we exhaustively enumerate the pathways followed by nets during folding and identify a crossover temperature [Formula: see text] below which nets fold via nonnative contacts (bonds must break before the net can fold completely) and above which nets fold via native contacts (newly formed bonds are also present in the folded structure). Folding above [Formula: see text] shows a universal balance between reduction of entropy via the elimination of internal degrees of freedom when bonds are formed and gain in potential energy via local, cooperative edge binding. Exploiting this universality, we devised a numerical method to efficiently compute all high-temperature folding pathways for any net, allowing us to predict, among the combined 86,760 nets for the remaining Platonic solids, those with highest folding propensity. Our results provide a general heuristic for the design of 2D objects to stochastically fold into target 3D geometries and suggest a mechanism by which geometry and folding propensity are related above [Formula: see text], where native bonds dominate folding.}, } @article {pmid29970419, year = {2018}, author = {Gourse, RL and Bouveret, E}, title = {Linking glucose metabolism to the stringent response through the PTS.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7454-7455}, pmid = {29970419}, issn = {1091-6490}, support = {R01 GM037048/GM/NIGMS NIH HHS/United States ; }, mesh = {*Carbohydrate Metabolism ; Glucose ; *Phosphoenolpyruvate Sugar Phosphotransferase System ; }, } @article {pmid29970418, year = {2018}, author = {Hu, Y and Ji, S and Jin, Y and Feng, L and Stanley, HE and Havlin, S}, title = {Local structure can identify and quantify influential global spreaders in large scale social networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7468-7472}, pmid = {29970418}, issn = {1091-6490}, abstract = {Measuring and optimizing the influence of nodes in big-data online social networks are important for many practical applications, such as the viral marketing and the adoption of new products. As the viral spreading on a social network is a global process, it is commonly believed that measuring the influence of nodes inevitably requires the knowledge of the entire network. Using percolation theory, we show that the spreading process displays a nucleation behavior: Once a piece of information spreads from the seeds to more than a small characteristic number of nodes, it reaches a point of no return and will quickly reach the percolation cluster, regardless of the entire network structure; otherwise the spreading will be contained locally. Thus, we find that, without the knowledge of the entire network, any node's global influence can be accurately measured using this characteristic number, which is independent of the network size. This motivates an efficient algorithm with constant time complexity on the long-standing problem of best seed spreaders selection, with performance remarkably close to the true optimum.}, } @article {pmid29970417, year = {2018}, author = {Catalá, R and Salinas, J}, title = {Tailoring crop nutrition to fight weeds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7456-7458}, pmid = {29970417}, issn = {1091-6490}, mesh = {Agriculture ; *Crops, Agricultural ; Herbicides ; *Plant Weeds ; }, } @article {pmid29970416, year = {2018}, author = {Allison, EH and Mills, DJ}, title = {Counting the fish eaten rather than the fish caught.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7459-7461}, pmid = {29970416}, issn = {1091-6490}, mesh = {Animals ; *Eating ; *Fishes ; }, } @article {pmid29970415, year = {2018}, author = {Kim, J and Williams, FJ and Dreger, DL and Plassais, J and Davis, BW and Parker, HG and Ostrander, EA}, title = {Genetic selection of athletic success in sport-hunting dogs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7212-E7221}, pmid = {29970415}, issn = {1091-6490}, mesh = {*Alleles ; Animals ; Dogs/*genetics/metabolism ; Muscle Proteins/*genetics/metabolism ; Nerve Tissue Proteins/*genetics/metabolism ; *Running ; *Selection, Genetic ; }, abstract = {Modern dogs are distinguished among domesticated species by the vast breadth of phenotypic variation produced by strong and consistent human-driven selective pressure. The resulting breeds reflect the development of closed populations with well-defined physical and behavioral attributes. The sport-hunting dog group has long been employed in assistance to hunters, reflecting strong behavioral pressures to locate and pursue quarry over great distances and variable terrain. Comparison of whole-genome sequence data between sport-hunting and terrier breeds, groups at the ends of a continuum in both form and function, reveals that genes underlying cardiovascular, muscular, and neuronal functions are under strong selection in sport-hunting breeds, including ADRB1, TRPM3, RYR3, UTRN, ASIC3, and ROBO1 We also identified an allele of TRPM3 that was significantly associated with increased racing speed in Whippets, accounting for 11.6% of the total variance in racing performance. Finally, we observed a significant association of ROBO1 with breed-specific accomplishments in competitive obstacle course events. These results provide strong evidence that sport-hunting breeds have been adapted to their occupations by improved endurance, cardiac function, blood flow, and cognitive performance, demonstrating how strong behavioral selection alters physiology to create breeds with distinct capabilities.}, } @article {pmid29970233, year = {2018}, author = {Roach, NT and Du, A and Hatala, KG and Ostrofsky, KR and Reeves, JS and Braun, DR and Harris, JWK and Behrensmeyer, AK and Richmond, BG}, title = {Pleistocene animal communities of a 1.5 million-year-old lake margin grassland and their relationship to Homo erectus paleoecology.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {70-83}, doi = {10.1016/j.jhevol.2018.04.014}, pmid = {29970233}, issn = {1095-8606}, abstract = {The ecological and selective forces that sparked the emergence of Homo's adaptive strategy remain poorly understood. New fossil and archaeological finds call into question previous interpretations of the grade shift that drove our ancestors' evolutionary split from the australopiths. Furthermore, issues of taphonomy and scale have limited reconstructions of the hominin habitats and faunal communities that define the environmental context of these behavioral changes. The multiple ∼1.5 Ma track surfaces from the Okote Member of the Koobi Fora Formation at East Turkana provide unique windows for examining hominin interactions with the paleoenvironment and associated faunas at high spatiotemporal resolution. These surfaces preserve the tracks of many animals, including cf. Homo erectus. Here, we examine the structure of the animal community that inhabited this landscape, considering effects of preservation bias by comparing the composition of the track assemblage to a skeletal assemblage from the same time and place. We find that the track and skeletal assemblages are similar in their representation of the vertebrate paleocommunity, with comparable levels of taxonomic richness and diversity. Evenness (equitability of the number of individuals per taxon) differs between the two assemblages due to the very different circumstances of body fossil versus track preservation. Both samples represent diverse groups of taxa including numerous water-dependent species, consistent with geological interpretations of the track site environments. Comparisons of these assemblages also show a pattern of non-random hominin association with a marginal lacustrine habitat relative to other vertebrates in the track assemblage. This evidence is consistent with behavior that included access to aquatic foods and possibly hunting by H. erectus in lake margins/edaphic grasslands. Such behaviors may signal the emergence of the adaptative strategies that define our genus.}, } @article {pmid29970197, year = {2018}, author = {Christian, SJ and Boama, V and Satti, H and Ramawat, J and Elhadd, TA and Ashawesh, K and Dukhan, K and Beer, S}, title = {Metformin or insulin: logical treatment in women with gestational diabetes in the Middle East, our experience.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {426}, pmid = {29970197}, issn = {1756-0500}, mesh = {Adult ; Diabetes, Gestational/*drug therapy ; Female ; Humans ; Hypoglycemic Agents/*therapeutic use ; Insulin/*therapeutic use ; Metformin/*therapeutic use ; Middle East ; Pregnancy ; Pregnancy Outcome ; Prospective Studies ; Qatar ; Young Adult ; }, abstract = {OBJECTIVE: The debate still continues about the preferred modality of treatment of gestational diabetes requiring pharmacological treatment. Insulin was previously considered as the gold standard, but the National Institute of Health and Care Excellence now recommend metformin as the first line drug of choice. The pharmacological management of gestational diabetes mellitus in the Middle East with its high risk population has not been widely published. We aim to evaluate the safety and efficacy of using metformin in comparison to insulin, in our group of patients, and to study key associated morbidities.

RESULTS: A total of 291 women registered in the clinic during the study period. One hundred and twenty-one (121) were women with gestational diabetes Mellitus requiring medical therapy. Among them, 107 delivered at term. Ninety (84%) women received metformin. Additional insulin was required in 32% of these patients. There was a significant difference in the birth weight of babies in the metformin with insulin group of 207 g (p value 0.04) in favour of metformin. There was no significant difference in maternal or neonatal morbidities between the groups. Metformin was thus found to be a safe, practical and cost effective medication to be offered to our population.}, } @article {pmid29970194, year = {2018}, author = {Baños-Lara, MDR and Zabaleta, J and Garai, J and Baddoo, M and Guerrero-Plata, A}, title = {Comparative analysis of miRNA profile in human dendritic cells infected with respiratory syncytial virus and human metapneumovirus.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {432}, pmid = {29970194}, issn = {1756-0500}, support = {PFUND-939//Louisiana State University/ ; P01CA214091//Foundation for the National Institutes of Health/ ; P20 CA202922/CA/NCI NIH HHS/United States ; P30GM110760//National Institute of General Medical Sciences/ ; P30 GM110760/GM/NIGMS NIH HHS/United States ; CIA-140082//Flight Attendant Medical Research Institute/ ; P20CA202922//Foundation for the National Institutes of Health/ ; P01 CA214091/CA/NCI NIH HHS/United States ; }, mesh = {Child ; *Dendritic Cells ; Humans ; Metapneumovirus/*metabolism ; MicroRNAs/*metabolism ; Paramyxoviridae Infections/*metabolism ; Respiratory Syncytial Virus Infections/*metabolism ; Respiratory Syncytial Virus, Human ; }, abstract = {OBJECTIVE: Human metapneumovirus (HMPV) and respiratory syncytial virus (RSV) are responsible for respiratory diseases, mostly in children. Despite the clinical and epidemiological similarities between these two pneumoviruses, they elicit different immune responses. This work aims to further our understanding of the differential immune response induced by these respiratory viruses by determining the changes of small non-coding RNAs (miRNAs), which regulate gene expression and are involved in numerous cellular processes including the immune system.

RESULTS: In the present study, we analyzed the expression of miRNA transcripts of human dendritic cells infected with RSV or HMPV by high throughput sequencing using Illumina sequencing technology. Further validation of miRNA expression by quantitative polymerase chain reaction indicated that HMPV infection up-regulated the expression of 2 miRNAs (hsa-miR-182-5p and hsa-miR-4634), while RSV infection induced significant expression of 3 miRNAs (hsa-miR-4448, hsa-miR-30a-5p and hsa-miR-4634). The predominant miRNA induced by both viruses was hsa-miR-4634.}, } @article {pmid29970192, year = {2018}, author = {Hesse, M and Stamm, A and Weber, R and Glünder, G}, title = {Efficacy of a Salmonella live vaccine for turkeys in different age groups and antibody response of vaccinated and non-vaccinated turkeys.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {431}, pmid = {29970192}, issn = {1756-0500}, mesh = {Animals ; *Antibodies, Bacterial ; Antibody Formation ; Egg Hypersensitivity ; Europe ; Female ; Germany ; Humans ; Poultry Diseases/*prevention & control ; Salmonella Infections, Animal/*prevention & control ; Salmonella Vaccines/*immunology ; Turkeys/*microbiology ; Zoonoses ; }, abstract = {OBJECTIVE: Human Salmonellosis continues to be one of the most important foodborne zoonoses worldwide, although a decrease in case numbers has been noted in recent years. It is a foodborne zoonotic infection most commonly associated with the consumption of raw egg products but also with meat consumption including the consumption of poultry products. Turkey flocks in Europe have been reported to be affected by Salmonella infection, too. The present study examines the efficacy of a newly licensed Salmonella life vaccine in reducing infections with the Salmonella serovars Typhimurium and Enteritidis in turkeys. Turkeys were vaccinated the first day of life and at the age of 6 and 16 weeks. Groups of birds which had received different numbers of vaccinations were then submitted to challenge trials with either SE or ST.

RESULTS: In vaccinated birds Salmonella counts in liver and spleen and, less effectively, in caecum were reduced compared to unvaccinated birds. In several groups serum antibody-titers were statistically significantly higher in vaccinated turkeys than in non-vaccinated ones at day seven post infection, but only in one out of six groups at day 14 post infection.}, } @article {pmid29970190, year = {2018}, author = {Segarra, VA and Hughes, NM and Ackerman, KM and Grider, MH and Lyda, T and Vigueira, PA}, title = {Student performance on the Test of Scientific Literacy Skills (TOSLS) does not change with assignment of a low-stakes grade.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {422}, pmid = {29970190}, issn = {1756-0500}, mesh = {*Educational Measurement ; Educational Status ; Female ; Humans ; *Literacy ; Male ; *Students ; Universities ; }, abstract = {OBJECTIVE: Response-validated multiple-choice assessments are used in college courses to assess student learning gains. The ability of a test to accurately reflect student learning gains is highly dependent on the students' effort. Within our institution, lackluster student effort is common on response-validated multiple-choice concept assessments that are not included as a portion of the semester grade but are used to inform curricular changes. Thus, we set out to determine whether increasing testing stakes by assigning a grade on student performance had an effect on student score and self-reported effort. The Test of Scientific Literacy Skills (TOSLS) is a response-validated multiple-choice assessment used to measure scientific literacy in undergraduates. We administered the TOSLS to students enrolled in a general education Biology course, both during the first 2 weeks (pretest) and the last 2 weeks (posttest) of the course.

RESULTS: Self-reported effort and TOSLS performance were significantly correlated in the ungraded cohort. This relationship did not exist in the graded sections. Our data indicate that assigning a low-stakes grade has no significant effect on mean student performance or self-reported effort on the TOSLS within our general education course.}, } @article {pmid29970187, year = {2018}, author = {Kain, J and Leyton, B and Soto-Sánchez, J and Concha, F}, title = {In preschool children, physical activity during school time can significantly increase by intensifying locomotor activities during physical education classes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {438}, pmid = {29970187}, issn = {1756-0500}, mesh = {Child, Preschool ; Exercise ; Female ; Humans ; Locomotion ; Male ; *Motor Skills ; *Physical Education and Training ; Schools ; }, abstract = {OBJECTIVES: After categorizing preschool children into "active and low active" according to their moderate and vigorous physical activity (MVPA) in PE classes (PE), we compared these two groups within each sex and by sex in: (a) % MVPA and MVPA minutes accrued from each fundamental motor skill (FMS) during PE and (b) % MVPA during school time.

RESULTS: 532 children (mean age 5.2 years, 50% girls) were selected from a nationwide program which provides 3 weekly PE. Children wore accelerometers during one school day which included PE. We recorded the type and duration of each activity indicated by the teacher, classifying each one into the corresponding FMS, extracting its MVPA minutes from the accelerometer software. Children were categorized into active and low active. Comparisons used T-tests. In PE, active children accumulate 40 and 36 percentage points (pp) more MVPA minutes (boys and girls respectively), while during school time, 4 pp more in each sex. Girls are significantly less active. Just considering locomotion, active boys and girls accumulate 11 more MVPA minutes during PE. Active boys surpass the MVPA guideline for PE, while active girls almost reach it. Low active children (especially girls) should intensify locomotor activities during PE.}, } @article {pmid29970182, year = {2018}, author = {Starr, EP and Shi, S and Blazewicz, SJ and Probst, AJ and Herman, DJ and Firestone, MK and Banfield, JF}, title = {Stable isotope informed genome-resolved metagenomics reveals that Saccharibacteria utilize microbially-processed plant-derived carbon.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {122}, pmid = {29970182}, issn = {2049-2618}, mesh = {Avena/metabolism/*microbiology ; Bacteria/*genetics/*metabolism ; Carbon/metabolism ; Carbon Dioxide/analysis/*chemistry ; DNA, Bacterial/*biosynthesis/genetics ; Energy Metabolism/*genetics ; Genome, Bacterial/*genetics ; Isotope Labeling ; Metagenomics ; Plant Roots/microbiology ; RNA, Bacterial/*biosynthesis/genetics ; Rhizosphere ; Soil Microbiology ; Symbiosis ; }, abstract = {BACKGROUND: The transformation of plant photosynthate into soil organic carbon and its recycling to CO2 by soil microorganisms is one of the central components of the terrestrial carbon cycle. There are currently large knowledge gaps related to which soil-associated microorganisms take up plant carbon in the rhizosphere and the fate of that carbon.

RESULTS: We conducted an experiment in which common wild oats (Avena fatua) were grown in a 13CO2 atmosphere and the rhizosphere and non-rhizosphere soil was sampled for genomic analyses. Density gradient centrifugation of DNA extracted from soil samples enabled distinction of microbes that did and did not incorporate the 13C into their DNA. A 1.45-Mbp genome of a Saccharibacteria (TM7) was identified and, despite the microbial complexity of rhizosphere soil, curated to completion. The genome lacks many biosynthetic pathways, including genes required to synthesize DNA de novo. Rather, it requires externally derived nucleotides for DNA and RNA synthesis. Given this, we conclude that rhizosphere-associated Saccharibacteria recycle DNA from bacteria that live off plant exudates and/or phage that acquired 13C because they preyed upon these bacteria and/or directly from the labeled plant DNA. Isotopic labeling indicates that the population was replicating during the 6-week period of plant growth. Interestingly, the genome is ~ 30% larger than other complete Saccharibacteria genomes from non-soil environments, largely due to more genes for complex carbon utilization and amino acid metabolism. Given the ability to degrade cellulose, hemicellulose, pectin, starch, and 1,3-β-glucan, we predict that this Saccharibacteria generates energy by fermentation of soil necromass and plant root exudates to acetate and lactate. The genome also encodes a linear electron transport chain featuring a terminal oxidase, suggesting that this Saccharibacteria may respire aerobically. The genome encodes a hydrolase that could breakdown salicylic acid, a plant defense signaling molecule, and genes to interconvert a variety of isoprenoids, including the plant hormone zeatin.

CONCLUSIONS: Rhizosphere Saccharibacteria likely depend on other bacteria for basic cellular building blocks. We propose that isotopically labeled CO2 is incorporated into plant-derived carbon and then into the DNA of rhizosphere organisms capable of nucleotide synthesis, and the nucleotides are recycled into Saccharibacterial genomes.}, } @article {pmid29970180, year = {2018}, author = {Hashmi, AA and Hussain, ZF and Hashmi, SK and Irfan, M and Khan, EY and Faridi, N and Khan, A and Edhi, MM}, title = {Immunohistochemical over expression of p53 in head and neck Squamous cell carcinoma: clinical and prognostic significance.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {433}, pmid = {29970180}, issn = {1756-0500}, mesh = {Adaptor Proteins, Signal Transducing ; Adult ; Carcinoma, Squamous Cell/diagnosis/*metabolism ; Female ; Head and Neck Neoplasms/diagnosis/*metabolism ; Humans ; Immunohistochemistry ; Male ; Middle Aged ; Prognosis ; Retrospective Studies ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {OBJECTIVE: Immunohistochemical over expression of p53 is considered as a marker of poor prognosis in many cancers. Therefore, we aimed to evaluate immunohistochemical overexpression of p53 in 121 cases of head and neck Squamous cell carcinoma and its association with various clinicopathologic features and survival.

RESULTS: Total 66.1% (80 cases) expressed positive p53 expression, 34% (29 cases) revealed no p53 expression, while focal positive p53 expression was noted in 9.9% (12 Cases). Moreover, high p53 expression (> 70%) was noted in 26.4% (32 cases), while 19% (23 cases) showed 51-70% p53 expression. On the basis of intensity of p53 staining; strong p53 expression was noted in 39.7% (48 cases), while 24.8% (30 cases) and 10.7% (13 cases) revealed intermediate and weak p53 expression respectively. Significant association of p53 intensity of expression with extranodal extension and higher tumor grade (grades II and III) was noted. p53 is useful prognostic biomarker in head and neck Squamous cell carcinoma and therefore we suggest that more large scale studies are needed to evaluate its prognostic significance in our population.}, } @article {pmid29970178, year = {2018}, author = {Wiesner-Hanks, T and Stewart, EL and Kaczmar, N and DeChant, C and Wu, H and Nelson, RJ and Lipson, H and Gore, MA}, title = {Image set for deep learning: field images of maize annotated with disease symptoms.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {440}, pmid = {29970178}, issn = {1756-0500}, support = {1527232//National Science Foundation/ ; }, mesh = {Algorithms ; *Data Curation ; *Deep Learning ; Humans ; *Plant Breeding ; Plant Diseases ; *Zea mays ; }, abstract = {OBJECTIVES: Automated detection and quantification of plant diseases would enable more rapid gains in plant breeding and faster scouting of farmers' fields. However, it is difficult for a simple algorithm to distinguish between the target disease and other sources of dead plant tissue in a typical field, especially given the many variations in lighting and orientation. Training a machine learning algorithm to accurately detect a given disease from images taken in the field requires a massive amount of human-generated training data.

DATA DESCRIPTION: This data set contains images of maize (Zea mays L.) leaves taken in three ways: by a hand-held camera, with a camera mounted on a boom, and with a camera mounted on a small unmanned aircraft system (sUAS, commonly known as a drone). Lesions of northern leaf blight (NLB), a common foliar disease of maize, were annotated in each image by one of two human experts. The three data sets together contain 18,222 images annotated with 105,705 NLB lesions, making this the largest publicly available image set annotated for a single plant disease.}, } @article {pmid29970171, year = {2018}, author = {Arokiaraj, MC}, title = {A novel method of inducing thrombosis in target arteries using coronary stents for therapeutic occlusion.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {429}, pmid = {29970171}, issn = {1756-0500}, mesh = {Adult ; Arteries ; *Embolization, Therapeutic ; Female ; Heparin ; Humans ; Male ; Middle Aged ; *Stents ; *Thrombosis ; }, abstract = {OBJECTIVES: Peripheral artery embolizations are often required for therapeutic purposes. The therapeutic embolizations are usually performed using embolization particles and coils. These procedures are also associated with complications. Coils and their delivery cables, and the expertise are not always available in all catheterization centers. Hence, a novel, simple controlled technique for arterial closure would be useful in emergency settings.

RESULTS: Following is a report of seven cases where embolization was performed successfully on an emergency basis after stenting using coronary stents for better closure of the target artery. Six patients underwent bronchial artery embolization for recurrent massive hemoptysis, and one another patient had pseudoaneurysm following percutaneous nephrolithotomy, and presented with hematuria and persistent and increasing blood discharge in drainage catheter. The stents were deployed in the target artery using 6F Judkin's diagnostic catheter over the 014 wires, which are easily available in all cardiac catheterization laboratories. This is a novel method to establish a metal platform inside the target arteries using coronary stents for better closure of the target arteries in combination with embolization techniques. The procedures were performed as lifesaving measures when small coils and the delivery cables were not available at the time of the procedures.}, } @article {pmid29970169, year = {2018}, author = {Tadesse, H and Desta, K and Kinde, S and Hassen, F and Gize, A}, title = {Errors in the Hematology Laboratory at St. Paul's Hospital Millennium Medical College, Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {420}, pmid = {29970169}, issn = {1756-0500}, support = {1//Addis Ababa University/ ; }, mesh = {Cross-Sectional Studies ; Ethiopia ; Hematology ; Hospitals ; Humans ; *Laboratories, Hospital ; *Medical Errors ; }, abstract = {OBJECTIVE: The objective of this study was to determine the magnitude of pre-analytical, analytical and post-analytical laboratory errors in hematology tests.

RESULTS: A total of 2606 hematology requests were studied. Out of the total, 562 (21.6%) pre-analytic, 14 (0.5%) analytical and 168 (6.4%) post-analytical errors were recorded which contribute a total frequency of 75.5, 1.9 and 22.6%, respectively. The name of the physician requesting the test was not provided on 2215 (85%) of request forms and 1827 (70.1%) of the request forms were unaccompanied with proper clinical details of the patient. Essential information required on the request forms was often missed. Close communication between clinicians and laboratory personnel is the key to improve laboratory quality in general.}, } @article {pmid29970163, year = {2018}, author = {Yizengaw, E and Getahun, T and Geta, M and Mulu, W and Ashagrie, M and Hailu, D and Tedila, S}, title = {Sero-prevalence of hepatitis B virus infection and associated factors among health care workers and medical waste handlers in primary hospitals of North-west Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {437}, pmid = {29970163}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; *Health Personnel ; Hepatitis B/*diagnosis/epidemiology ; Hepatitis B Surface Antigens ; Hepatitis B virus/immunology/*isolation & purification ; Humans ; Male ; Medical Waste ; Middle Aged ; Risk Factors ; Seroepidemiologic Studies ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this cross-sectional study was to determined the sero-prevalence of HBV infection and associated factors among health care workers and medical waste handlers in primary hospitals of North-west Ethiopia.

RESULTS: A total of 388 study participants were included in this study. Of which, 268 (69%) were health care workers and 120 (31%) were medical waste handlers. Males accounted 54.9% and the mean age for all study participants was 28.3 (standard deviation = 6.9). Hepatitis B virus surface antigen (HBsAg) was detected in 2.6% health care workers and 2.5% medical waste handlers and the overall hepatitis B virus infection was 10 (2.6%). High rate of hepatitis B virus infection was detected in single participants and those in the age group of 30-40 years were more infected (6.6%). History of contact with HBV infected case (8.3%) (AOR = 6.8, 95% CI = 1.6-28.5, P = 0.009) and history of jaundice (15.4%) (AOR = 10.5, 95% CI = 2.1-12.2, P = 0.03) were statistically associated factors for HBV infection. More than half (54.4%) of the study participants did not take training on infection and 9 (4.3%) of them were positive for HBsAg (COR = 1.3, 95% CI = 0.0.02-1.02, P = 0.052).}, } @article {pmid29970162, year = {2018}, author = {Njim, T and Agbor, VN}, title = {Adolescent deliveries in rural Cameroon: comparison of delivery outcomes between primipara and multipara adolescents.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {427}, pmid = {29970162}, issn = {1756-0500}, mesh = {Adolescent ; Cameroon ; *Delivery, Obstetric ; Female ; Humans ; Infant ; Infant, Newborn ; *Parity ; Pregnancy ; Pregnancy Outcome ; *Pregnancy in Adolescence ; Retrospective Studies ; }, abstract = {OBJECTIVE: Adolescent pregnancies are high risk and deliveries in this age group are usually associated with adverse outcomes. The perception that multiparous adolescents have better delivery outcomes than primiparous counterparts is not uncommon. We sought to determine if multiparous adolescents were precluded from having adverse delivery outcomes when compared to primiparous adolescents. The data used for the analysis is a side product from a published project aimed at mapping the epidemiology of adolescent deliveries in the Oku health district.

RESULTS: From an 8-year (2009-2016) retrospective register analysis of data from two primary healthcare facilities in the Oku health district-a rural area in Cameroon, the prevalence of multiparous adolescent deliveries was 21.5% (78/363). After multivariable analyses, and adjusting for age, sex of baby, gestational age, marital status and HIV status, primiparous adolescents were more likely to have low birth weight infants (LBW) (OR: 3.2; 95% CI 1.1, 9.7; p = 0.04) when compared with multiparous adolescents. Though primiparous adolescents were more likely to have LBW infants than multiparous adolescents, this group of mothers are generally ill-equipped to handle pregnancies and adolescent-friendly programs are necessary to decrease the associated burden.}, } @article {pmid29970161, year = {2018}, author = {Tesfaye, TD}, title = {Coping strategies among nurses in South-west Ethiopia: descriptive, institution-based cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {421}, pmid = {29970161}, issn = {1756-0500}, mesh = {*Adaptation, Psychological ; Cross-Sectional Studies ; Ethiopia ; Humans ; Nurses/*psychology ; Social Support ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: This study aimed to describe coping strategies for job stress among nurses working in Jimma Zone public hospitals, South-west Ethiopia. The study conducted from March to April 2014 through census using English version structured self-administered questionnaire.

RESULT: This study indicated percentage mean overall score of 65.07% for adaptive coping approach and 56.86% for a maladaptive approach. Nurses mostly used coping strategy were; just concentrating on what they have to do, make a plan of action and following it, developing coworker/peer support, and having a close friend to tell. While, coping strategy that least used among nurses were; do not want to come to work when stressed, directly expressing anger on family or friends, trying to feel better by taking drinks like tea, coffee, soft drinks more than usual and accept the situation because there is nothing to do. In summary, an adaptive approach was dominant style; social support and plan-full problem solving were the most preferred strategies. While escape-avoidance coping strategy least used. Further researches need to be conducted to explore its predictors.}, } @article {pmid29970159, year = {2018}, author = {Jabaley, CS and Groff, RF and Sharifpour, M and Raikhelkar, JK and Blum, JM}, title = {Modes of mechanical ventilation vary between hospitals and intensive care units within a university healthcare system: a retrospective observational study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {425}, pmid = {29970159}, issn = {1756-0500}, mesh = {*Academic Medical Centers ; Humans ; *Intensive Care Units ; *Respiration, Artificial ; Retrospective Studies ; Universities ; *Ventilator Weaning ; }, abstract = {OBJECTIVE: As evidence-based guidance to aid clinicians with mechanical ventilation mode selection is scant, we sought to characterize the epidemiology thereof within a university healthcare system and hypothesized that nonconforming approaches could be readily identified. We conducted an exploratory retrospective observational database study of routinely recorded mechanical ventilation parameters between January 1, 2010 and December 31, 2016 from 12 intensive care units. Mode epoch count proportions were examined using Chi squared and Fisher exact tests as appropriate on an inter-unit basis with outlier detection for two test cases via post hoc pairwise analyses of a binomial regression model.

RESULTS: Final analysis included 559,734 mode epoch values. Significant heterogeneity was demonstrated between individual units (P < 0.05 for all comparisons). One unit demonstrated heightened utilization of high-frequency oscillatory ventilation, and three units demonstrated frequent synchronized intermittent mandatory ventilation utilization. Assist control ventilation was the most commonly recorded mode (51%), followed by adaptive support ventilation (23.1%). Volume-controlled modes were about twice as common as pressure-controlled modes (64.4% versus 35.6%). Our methodology provides a means by which to characterize the epidemiology of mechanical ventilation approaches and identify nonconforming practices. The observed variability warrants further clinical study about contributors and the impact on relevant outcomes.}, } @article {pmid29970157, year = {2018}, author = {Astill, J and Alkie, T and Yitbarek, A and Taha-Abdelaziz, K and Bavananthasivam, J and Nagy, É and Petrik, JJ and Sharif, S}, title = {Induction of immune response in chickens primed in ovo with an inactivated H9N2 avian influenza virus vaccine.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {428}, pmid = {29970157}, issn = {1756-0500}, mesh = {Animals ; Antibodies, Viral ; Antibody Formation ; Chickens ; Influenza A Virus, H9N2 Subtype/*immunology ; Influenza Vaccines/*immunology ; Influenza in Birds/*immunology ; }, abstract = {OBJECTIVE: Infection of chickens with low pathogenic avian influenza virus, such as H9N2 virus, culminates in decreased egg production and increased mortality and morbidity if co-infection with other respiratory pathogens occurs. We have previously observed the induction of antibody- and cell-mediated immune responses after intramuscular administration of an H9N2 beta-propiolactone inactivated virus vaccine to chickens. Given the fact that in ovo vaccination represents a practical option for vaccination against H9N2 AIV in chickens, in the current study, we set out to characterize immune responses in chickens against a beta-propiolactone inactivated H9N2 virus vaccine after primary vaccination in ovo on embryonic day 18, and secondary intramuscular vaccination on day 14 post-hatch. We also included the Toll-like receptor 21 ligand, CpG ODN 2007, and an oil emulsion adjuvant, AddaVax™, as adjuvants for the vaccines.

RESULTS: Antibody-mediated immune responses were observed after administering the secondary intramuscular vaccine. Cell-mediated immune responses were observed in chickens that received the beta-propiolactone inactivated H9N2 virus combined with AddaVax™. Our results demonstrate that adaptive immune responses can be induced in chickens after a primary in ovo vaccination and secondary intramuscular vaccination.}, } @article {pmid29970154, year = {2018}, author = {Cornet, L and Wilmotte, A and Javaux, EJ and Baurain, D}, title = {A constrained SSU-rRNA phylogeny reveals the unsequenced diversity of photosynthetic Cyanobacteria (Oxyphotobacteria).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {435}, pmid = {29970154}, issn = {1756-0500}, support = {FP7/308074//European Research Council Stg ELITE/ ; SD/BA/03A//BELSPO project CCAMBIO/ ; SFRD-12/04//Crédit de démarrage 2012 - ULiege/ ; CDR J.0080.15//Crédit de recherche 2014 - FNRS/ ; }, mesh = {Base Sequence ; Cyanobacteria/*genetics ; Photosynthesis/*genetics ; *Phylogeny ; RNA, Ribosomal/*analysis ; }, abstract = {OBJECTIVE: Cyanobacteria are an ancient phylum of prokaryotes that contain the class Oxyphotobacteria. This group has been extensively studied by phylogenomics notably because it is widely accepted that Cyanobacteria were responsible for the spread of photosynthesis to the eukaryotic domain. The aim of this study was to evaluate the fraction of the oxyphotobacterial diversity for which sequenced genomes are available for genomic studies. For this, we built a phylogenomic-constrained SSU rRNA (16S) tree to pinpoint unexploited clusters of Oxyphotobacteria that should be targeted for future genome sequencing, so as to improve our understanding of Oxyphotobacteria evolution.

RESULTS: We show that only a little fraction of the oxyphotobacterial diversity has been sequenced so far. Indeed 31 rRNA clusters of the 60 composing the photosynthetic Cyanobacteria have a fraction of sequenced genomes < 1%. This fraction remains low (min = 1%, median = 11.1%, IQR = 7.3%) within the remaining "sequenced" clusters that already contain some representative genomes. The "unsequenced" clusters are scattered across the whole Oxyphotobacteria tree, at the exception of very basal clades. Yet, these clades still feature some (sub)clusters without any representative genome. This last result is especially important, as these basal clades are prime candidate for plastid emergence.}, } @article {pmid29970151, year = {2018}, author = {Sandoval Salinas, ML and Sandoval, JD and Colombo, EM and Barquez, RM}, title = {The pattern of color change in small mammal museum specimens: is it independent of storage histories given museum-specific conditions?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {424}, pmid = {29970151}, issn = {1756-0500}, support = {PICT 2014-1843//Fondo para la Investigación Científica y Tecnológica/ ; }, mesh = {Adult ; Animals ; Color ; Humans ; Lighting ; *Mammals ; Mice ; *Museums ; }, abstract = {OBJECTIVE: Determination of color and evaluating its variation form the basis for a broad range of research questions. For studies on taxonomy, systematics, etc., resorting to mammal specimens in museum collections has a number of advantages over using field specimens. However, if museum specimens are to be for studying color, they should accurately represent the color of live animals, or we should understand how they differ. Basically, this study addresses this question: How does coat color vary when dealing with specimens of Akodon budini (Budin's grass mouse, Thomas 1918), stored in one museum collection for different periods of time?

RESULTS: We measured color values through a spectroradiometer and a diffuse illumination cabin and used the reflectance values in the form of CIELab tri-stimulus values, considering CIE standard illuminant A. We observed that there is a relationship between specimen storage antiquity and pelage color and it seems that it is general for at least a number of small mammals and this could indicate a universal phenomenon across several mammal species and across several storage conditions. Our results, as others, emphasize the importance of considering storage time, among other circumstances, in research studies using mammal skins and where color is of importance.}, } @article {pmid29970150, year = {2018}, author = {Demilew, YM and Alem, AT and Emiru, AA}, title = {Dietary practice and associated factors among type 2 diabetic patients in Felege Hiwot Regional Referral Hospital, Bahir Dar, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {434}, pmid = {29970150}, issn = {1756-0500}, mesh = {Adult ; Cities ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 2 ; *Diet ; Ethiopia ; Female ; Humans ; Male ; Middle Aged ; }, abstract = {OBJECTIVE: Even if patient's dietary practice is a gold standard measure to manage type 2 diabetes, there is a limited study in the area. Therefore, the objective of this study was to assess dietary practice and associated factors among type 2 diabetic patients.

RESULT: The study revealed that only 35.9% of the patients had good dietary practice. Attending above primary education [AOR = 1.9, 95% CI (1.1, 3.2)], having family support [AOR = 2.6, 95% CI (1.6, 4.2)], and receiving nutrition education [AOR = 2.5, 95% CI (1.5, 4.2)] were independent predictors for good dietary practice. Thus, the findings indicate the need to improve a method of nutrition education both for the patients and their families. Moreover, the government needs to improve literacy rate of citizens.}, } @article {pmid29970146, year = {2018}, author = {Garzon-Rodriguez, JD and Obando-Lopez, C and Giraldo-Grueso, M and Sandoval-Reyes, N and Camacho, J and Umaña, JP}, title = {Mechanical circulatory support as bridge therapy for heart transplant: case series report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {430}, pmid = {29970146}, issn = {1756-0500}, mesh = {Adult ; Colombia ; *Extracorporeal Membrane Oxygenation ; Female ; Heart Failure ; *Heart Transplantation ; *Heart-Assist Devices ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Ventricular Function, Left ; }, abstract = {BACKGROUND: Mechanical circulatory support (MCS) represents an effective urgent therapy for patients with cardiac arrest or end-stage cardiac failure. However, its use in developing countries as a bridge therapy remains controversial due to costs and limited duration. This study presents five patients who underwent MSC as bridge therapy for heart transplantation in a developing country.

CASE PRESENTATION: We present five patients who underwent MCS as bridge therapy for heart transplant between 2010 and 2015 at Fundación Cardioinfantil-Instituto de Cardiología. Four were male, median age was 36 (23-50) years. One patient had an ischemic cardiomyopathy, one a lymphocytic myocarditis, two had electrical storms (recurrent ventricular tachycardia) and one an ischemic cardiomyopathy with an electrical storm. Extracorporeal life support (ECLS) was used in three patients, left ventricular assistance in one, and double ventricular assistance in one (Levitronix® Centrimag®). Median assistance time was 8 (2.5-13) days. Due to the inability of cardiopulmonary bypass weaning, two patients required ECLS after transplant. One patient died in the intensive care unit due to type I graft rejection. Endpoints assessed were 30-day mortality, duration of bridge therapy and complications related to MCS. Patients that died on ECLS, or were successfully weaned off ECLS were not included in this study.

CONCLUSIONS: MCS is often the only option of support for critically ill patients waiting for a heart transplant and could be considered as a short-term bridge therapy.}, } @article {pmid29970140, year = {2018}, author = {Tavernier, E and Chalayer, E and Cornillon, J and Pouvaret, A and Martignoles, JA and Casteillo, F and Terreaux, J and Daguenet, E and Guyotat, D}, title = {Fulminant hepatitis due to very severe sinusoidal obstruction syndrome (SOS/VOD) after autologous peripheral stem cell transplantation: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {436}, pmid = {29970140}, issn = {1756-0500}, mesh = {Hematopoietic Stem Cell Transplantation ; Hepatic Veno-Occlusive Disease/*complications ; Hepatitis/*etiology ; Humans ; Liver Failure, Acute/*etiology ; Male ; Middle Aged ; *Peripheral Blood Stem Cell Transplantation ; Positron Emission Tomography Computed Tomography ; }, abstract = {BACKGROUND: Hepatic veno-occlusive disease, also called sinusoidal obstruction syndrome (SOS/VOD), is a potentially fatal complication of allogeneic or autologous hematopoietic stem cell transplantation. A plethora of transplant and patient-related risk factors predispose to SOS/VOD and should be taken into account for prognosis assessment as well as for adequate therapeutic intervention.

CASE PRESENTATION: We describe the case of a mantle cell lymphoma patient who developed a fulminant hepatitis following oxaliplatin-containing intensive chemotherapy and autologous transplantation. This clinical manifestation was secondary to a very severe SOS/VOD. The patient did not exhibit the usual risk factors and presented a non-classical form with major cytolysis, thus puzzling SOS/VOD diagnosis in this context.

CONCLUSION: SOS has been previously reported after oxaliplatin-based chemotherapy regimens for colorectal cancers, in particular in patients with colorectal liver metastases. We therefore suspected a potential relationship with oxaliplatin-based regimen as a driver of SOS/VOD in a non-susceptible lymphoma patient. With regards to this case, clinicians and especially intensivists should be aware of this atypical presentation.}, } @article {pmid29970134, year = {2018}, author = {Guo, XH and Kan, Z and Liu, BW and Li, LL}, title = {A foodborne acute gastroenteritis outbreak caused by GII.P16-GII.2 norovirus in a boarding high school, Beijing, China: a case-control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {439}, pmid = {29970134}, issn = {1756-0500}, support = {201601026//Fangshan Science and Technology Committee/ ; }, mesh = {Beijing/epidemiology ; Caliciviridae Infections/*epidemiology ; Case-Control Studies ; Disease Outbreaks ; Gastroenteritis/*epidemiology ; Genotype ; Humans ; Norovirus/*isolation & purification ; Phylogeny ; }, abstract = {OBJECTIVE: In December 2017, an acute gastroenteritis outbreak involving 61 students occurred in a boarding high school in Beijing, China. We conducted an outbreak investigation immediately in order to determine the cause of this outbreak and provide effective control measures.

RESULTS: The laboratory inspection showed that this outbreak was caused by GII.P16-GII.2 norovirus. Risk factor analysis indicated that the lunch provided by Cafeteria 1 on Dec 12 might be the risk factor of the outbreak with an odds ratio (OR) of 3.800 (95% confidence interval [CI] 1.089-13.258). Additionally, a tray line server of Cafeteria 1 was found to have gastro-enteral symptoms recently. Based on the clinical symptoms and epidemiology investigation, the symptomatic server was considered to be the possible source of infection.}, } @article {pmid29970132, year = {2018}, author = {Khetan, RP and Stein, DA and Chaudhary, SK and Rauniyar, R and Upadhyay, BP and Gupta, UP and Gupta, BP}, title = {Profile of the 2016 dengue outbreak in Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {423}, pmid = {29970132}, issn = {1756-0500}, mesh = {Adult ; Animals ; Dengue/*epidemiology ; *Disease Outbreaks ; Female ; Humans ; Male ; Middle Aged ; Nepal/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: The objective of this study was to obtain clinical, virological and demographic data detailing the 2016 dengue outbreak in Nepal.

RESULTS: Dengue disease was first reported in Nepal in 2004 and several major outbreaks have occurred since then, with a significant impact on public health. An outbreak of dengue fever occurred in Nepal during June to November 2016, with a peak number of cases reported in September. 1473 patients with laboratory confirmed DENV infections visited or were admitted to hospitals during this period. The most common clinical symptoms included fever, headache, joint pain and thrombocytopenia. Serotyping of 75 serum samples from patients having fever for less than 4 days was carried out with a dengue virus (DENV) serotype-specific RT-PCR strategy. Our results indicate that the dengue outbreak in Nepal during 2016 was caused predominantly, if not exclusively, by DENV-1, representing a shift in the prevailing serotype from DENV-2, the dominant serotype characterizing the 2013 dengue epidemic in Nepal. Hopefully, this report will assist Nepalese public health agencies in developing improved dengue-related programs including mosquito-vector control, DENV surveillance, and diagnosis and treatment of dengue fever patients, in order to reduce the impact of future dengue epidemics.}, } @article {pmid29970070, year = {2018}, author = {Strome, B and Hsu, IS and Li Cheong Man, M and Zarin, T and Nguyen Ba, A and Moses, AM}, title = {Short linear motifs in intrinsically disordered regions modulate HOG signaling capacity.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {75}, pmid = {29970070}, issn = {1752-0509}, support = {MOP-119579//Canadian Institutes of Health Research/Canada ; PJT-148532//Canadian Institutes of Health Research/Canada ; }, abstract = {BACKGROUND: The effort to characterize intrinsically disordered regions of signaling proteins is rapidly expanding. An important class of disordered interaction modules are ubiquitous and functionally diverse elements known as short linear motifs (SLiMs).

RESULTS: To further examine the role of SLiMs in signal transduction, we used a previously devised bioinformatics method to predict evolutionarily conserved SLiMs within a well-characterized pathway in S. cerevisiae. Using a single cell, reporter-based flow cytometry assay in conjunction with a fluorescent reporter driven by a pathway-specific promoter, we quantitatively assessed pathway output via systematic deletions of individual motifs. We found that, when deleted, 34% (10/29) of predicted SLiMs displayed a significant decrease in pathway output, providing evidence that these motifs play a role in signal transduction. Assuming that mutations in SLiMs have quantitative effects on mechanisms of signaling, we show that perturbations of parameters in a previously published stochastic model of HOG signaling could reproduce the quantitative effects of 4 out of 7 mutations in previously unknown SLiMs.

CONCLUSIONS: Our study suggests that, even in well-characterized pathways, large numbers of functional elements remain undiscovered, and that challenges remain for application of systems biology models to interpret the effects of mutations in signaling pathways.}, } @article {pmid29970004, year = {2018}, author = {de Boer, CG and Regev, A}, title = {BROCKMAN: deciphering variance in epigenomic regulators by k-mer factorization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {253}, pmid = {29970004}, issn = {1471-2105}, support = {//CIHR/Canada ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {BACKGROUND: Variation in chromatin organization across single cells can help shed important light on the mechanisms controlling gene expression, but scale, noise, and sparsity pose significant challenges for interpretation of single cell chromatin data. Here, we develop BROCKMAN (Brockman Representation Of Chromatin by K-mers in Mark-Associated Nucleotides), an approach to infer variation in transcription factor (TF) activity across samples through unsupervised analysis of the variation in DNA sequences associated with an epigenomic mark.

RESULTS: BROCKMAN represents each sample as a vector of epigenomic-mark-associated DNA word frequencies, and decomposes the resulting matrix to find hidden structure in the data, followed by unsupervised grouping of samples and identification of the TFs that distinguish groups. Applied to single cell ATAC-seq, BROCKMAN readily distinguished cell types, treatments, batch effects, experimental artifacts, and cycling cells. We show that each variable component in the k-mer landscape reflects a set of co-varying TFs, which are often known to physically interact. For example, in K562 cells, AP-1 TFs were central determinant of variability in chromatin accessibility through their variable expression levels and diverse interactions with other TFs. We provide a theoretical basis for why cooperative TF binding - and any associated epigenomic mark - is inherently more variable than non-cooperative binding.

CONCLUSIONS: BROCKMAN and related approaches will help gain a mechanistic understanding of the trans determinants of chromatin variability between cells, treatments, and individuals.}, } @article {pmid29970003, year = {2018}, author = {Pan, X and Rijnbeek, P and Yan, J and Shen, HB}, title = {Prediction of RNA-protein sequence and structure binding preferences using deep convolutional and recurrent neural networks.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {511}, pmid = {29970003}, issn = {1471-2164}, support = {61671288//National Natural Science Foundation of China/ ; 61462018//National Natural Science Foundation of China/ ; }, mesh = {Algorithms ; Binding Sites ; Computational Biology/*methods ; *Neural Networks (Computer) ; Nucleic Acid Conformation ; Nucleotide Motifs ; Protein Binding ; RNA/*metabolism ; RNA-Binding Proteins/*metabolism ; User-Computer Interface ; }, abstract = {BACKGROUND: RNA regulation is significantly dependent on its binding protein partner, known as the RNA-binding proteins (RBPs). Unfortunately, the binding preferences for most RBPs are still not well characterized. Interdependencies between sequence and secondary structure specificities is challenging for both predicting RBP binding sites and accurate sequence and structure motifs detection.

RESULTS: In this study, we propose a deep learning-based method, iDeepS, to simultaneously identify the binding sequence and structure motifs from RNA sequences using convolutional neural networks (CNNs) and a bidirectional long short term memory network (BLSTM). We first perform one-hot encoding for both the sequence and predicted secondary structure, to enable subsequent convolution operations. To reveal the hidden binding knowledge from the observed sequences, the CNNs are applied to learn the abstract features. Considering the close relationship between sequence and predicted structures, we use the BLSTM to capture possible long range dependencies between binding sequence and structure motifs identified by the CNNs. Finally, the learned weighted representations are fed into a classification layer to predict the RBP binding sites. We evaluated iDeepS on verified RBP binding sites derived from large-scale representative CLIP-seq datasets. The results demonstrate that iDeepS can reliably predict the RBP binding sites on RNAs, and outperforms the state-of-the-art methods. An important advantage compared to other methods is that iDeepS can automatically extract both binding sequence and structure motifs, which will improve our understanding of the mechanisms of binding specificities of RBPs.

CONCLUSION: Our study shows that the iDeepS method identifies the sequence and structure motifs to accurately predict RBP binding sites. iDeepS is available at https://github.com/xypan1232/iDeepS .}, } @article {pmid29970002, year = {2018}, author = {Beretta, S and Patterson, MD and Zaccaria, S and Della Vedova, G and Bonizzoni, P}, title = {HapCHAT: adaptive haplotype assembly for efficiently leveraging high coverage in long reads.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {252}, pmid = {29970002}, issn = {1471-2105}, abstract = {BACKGROUND: Haplotype assembly is the process of assigning the different alleles of the variants covered by mapped sequencing reads to the two haplotypes of the genome of a human individual. Long reads, which are nowadays cheaper to produce and more widely available than ever before, have been used to reduce the fragmentation of the assembled haplotypes since their ability to span several variants along the genome. These long reads are also characterized by a high error rate, an issue which may be mitigated, however, with larger sets of reads, when this error rate is uniform across genome positions. Unfortunately, current state-of-the-art dynamic programming approaches designed for long reads deal only with limited coverages.

RESULTS: Here, we propose a new method for assembling haplotypes which combines and extends the features of previous approaches to deal with long reads and higher coverages. In particular, our algorithm is able to dynamically adapt the estimated number of errors at each variant site, while minimizing the total number of error corrections necessary for finding a feasible solution. This allows our method to significantly reduce the required computational resources, allowing to consider datasets composed of higher coverages. The algorithm has been implemented in a freely available tool, HapCHAT: Haplotype Assembly Coverage Handling by Adapting Thresholds. An experimental analysis on sequencing reads with up to 60 × coverage reveals improvements in accuracy and recall achieved by considering a higher coverage with lower runtimes.

CONCLUSIONS: Our method leverages the long-range information of sequencing reads that allows to obtain assembled haplotypes fragmented in a lower number of unphased haplotype blocks. At the same time, our method is also able to deal with higher coverages to better correct the errors in the original reads and to obtain more accurate haplotypes as a result.

AVAILABILITY: HapCHAT is available at http://hapchat.algolab.eu under the GNU Public License (GPL).}, } @article {pmid29970001, year = {2018}, author = {Lenz, H and Hein, A and Knoop, V}, title = {Plant organelle RNA editing and its specificity factors: enhancements of analyses and new database features in PREPACT 3.0.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {255}, pmid = {29970001}, issn = {1471-2105}, abstract = {BACKGROUND: Gene expression in plant chloroplasts and mitochondria is affected by RNA editing. Numerous C-to-U conversions, accompanied by reverse U-to-C exchanges in some plant clades, alter the genetic information encoded in the organelle genomes. Predicting and analyzing RNA editing, which ranges from only few sites in some species to thousands in other taxa, is bioinformatically demanding.

RESULTS: Here, we present major enhancements and extensions of PREPACT, a WWW-based service for analysing, predicting and cataloguing plant-type RNA editing. New features in PREPACT's core include direct GenBank accession query input and options to restrict searches to candidate U-to-C editing or to sites where editing has been documented previously in the references. The reference database has been extended by 20 new organelle editomes. PREPACT 3.0 features new modules "EdiFacts" and "TargetScan". EdiFacts integrates information on pentatricopeptide repeat (PPR) proteins characterized as site-specific RNA editing factors. PREPACT's editome references connect into EdiFacts, linking editing events to specific co-factors where known. TargetScan allows position-weighted querying for sequence motifs in the organelle references, optionally restricted to coding regions or sequences around editing sites, or in queries uploaded by the user. TargetScan is mainly intended to evaluate and further refine the proposed PPR-RNA recognition code but may be handy for other tasks as well. We present an analysis for the immediate sequence environment of more than 15,000 documented editing sites finding strong and different bias in the editome data sets.

CONCLUSIONS: We exemplarily present the novel features of PREPACT 3.0 aimed to enhance the analyses of plant-type RNA editing, including its new modules EdiFacts integrating information on characterized editing factors and TargetScan aimed to analyse RNA editing site recognition specificities.}, } @article {pmid29969991, year = {2018}, author = {Wu, DC and Yao, J and Ho, KS and Lambowitz, AM and Wilke, CO}, title = {Limitations of alignment-free tools in total RNA-seq quantification.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {510}, pmid = {29969991}, issn = {1471-2164}, support = {GM37949//National Institutes of Health (US)/ ; F1607//Welch Foundation (US)/ ; }, mesh = {Algorithms ; Area Under Curve ; High-Throughput Nucleotide Sequencing ; RNA/*chemistry/metabolism ; RNA, Ribosomal/chemistry/metabolism ; RNA, Transfer/chemistry/metabolism ; ROC Curve ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Alignment-free RNA quantification tools have significantly increased the speed of RNA-seq analysis. However, it is unclear whether these state-of-the-art RNA-seq analysis pipelines can quantify small RNAs as accurately as they do with long RNAs in the context of total RNA quantification.

RESULT: We comprehensively tested and compared four RNA-seq pipelines for accuracy of gene quantification and fold-change estimation. We used a novel total RNA benchmarking dataset in which small non-coding RNAs are highly represented along with other long RNAs. The four RNA-seq pipelines consisted of two commonly-used alignment-free pipelines and two variants of alignment-based pipelines. We found that all pipelines showed high accuracy for quantifying the expression of long and highly-abundant genes. However, alignment-free pipelines showed systematically poorer performance in quantifying lowly-abundant and small RNAs.

CONCLUSION: We have shown that alignment-free and traditional alignment-based quantification methods perform similarly for common gene targets, such as protein-coding genes. However, we have identified a potential pitfall in analyzing and quantifying lowly-expressed genes and small RNAs with alignment-free pipelines, especially when these small RNAs contain biological variations.}, } @article {pmid29969988, year = {2018}, author = {Xu, J and Kidder, BL}, title = {H4K20me3 co-localizes with activating histone modifications at transcriptionally dynamic regions in embryonic stem cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {514}, pmid = {29969988}, issn = {1471-2164}, support = {K22 HL126842/HL/NHLBI NIH HHS/United States ; 1K22HL126842-01A1//National Heart, Lung, and Blood Institute/ ; }, mesh = {Animals ; Cell Line ; Chromatin Immunoprecipitation ; Epigenomics ; Heterochromatin/metabolism ; Histones/genetics/*metabolism ; Methylation ; Mice ; Mouse Embryonic Stem Cells/cytology/metabolism ; Promoter Regions, Genetic ; RNA Polymerase II/metabolism ; Sequence Analysis, RNA ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Bivalent chromatin domains consisting of the activating histone 3 lysine 4 trimethylation (H3K4me3) and repressive histone 3 lysine 27 trimethylation (H3K27me3) histone modifications are enriched at developmental genes that are repressed in embryonic stem cells but active during differentiation. However, it is unknown whether another repressive histone modification, histone 4 lysine 20 trimethylation (H4K20me3), co-localizes with activating histone marks in ES cells.

RESULTS: Here, we describe the previously uncharacterized coupling of the repressive H4K20me3 heterochromatin mark with the activating histone modifications H3K4me3 and histone 3 lysine 36 trimethylation (H3K36me3), and transcriptional machinery (RNA polymerase II; RNAPII), in ES cells. These newly described bivalent domains consisting of H3K4me3/H4K20me3 are predominantly located in intergenic regions and near transcriptional start sites of active genes, while H3K36me3/H4K20me3 are located in intergenic regions and within gene body regions of active genes. Global sequential ChIP, also termed reChIP-Seq, confirmed the simultaneous presence of H3K4me3 and H4K20me3 at the same genomic regions in ES cells. Genes containing H3K4me3/H4K20me3 exhibit decreased RNAPII pausing and are poised for deactivation of RNAPII binding during differentiation relative to H3K4me3 marked genes. An evaluation of transcription factor (TF) binding motif enrichment revealed that DNA sequence may play a role in shaping the landscape of these novel bivalent domains. Moreover, H3K4me3/H4K20me3 and H3K36me3/H4K20me3 bound regions are enriched with repetitive LINE and LTR elements.

CONCLUSIONS: Overall, these findings highlight a previously undescribed subnetwork of ES cell transcriptional circuitry that utilizes dual marking of the repressive H4K20me3 mark with activating histone modifications.}, } @article {pmid29969987, year = {2018}, author = {Ebbs, ET and Loker, ES and Brant, SV}, title = {Phylogeography and genetics of the globally invasive snail Physa acuta Draparnaud 1805, and its potential to serve as an intermediate host to larval digenetic trematodes.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {103}, pmid = {29969987}, issn = {1471-2148}, support = {P30 GM110907/GM/NIGMS NIH HHS/United States ; R37 AI101438/AI/NIAID NIH HHS/United States ; DEB 1021427//National Science Foundation/International ; R37 AI101438/NH/NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; Genetic Variation ; Genetics, Population ; Host-Parasite Interactions/*genetics ; *Introduced Species ; Larva/physiology ; Phylogeny ; *Phylogeography ; Snails/*genetics/*parasitology ; Species Specificity ; Trematoda/*physiology ; }, abstract = {BACKGROUND: Physa acuta is a globally invasive freshwater snail native to North America. Prior studies have led to conflicting views of how P. acuta populations are connected and genetic diversity is partitioned globally. This study aims to characterize phylogeographic and population genetic structure within the native range of P. acuta, elucidate its invasion history and assess global patterns of genetic diversity. Further, using meta-analytic methods, we test the 'Enemy-Release hypothesis' within the P. acuta - digenetic trematode system. The 'Enemy-Release hypothesis' refers to the loss of native parasites following establishment of their host within an invasive range. Population genetic data is combined with surveys of trematode infections to map range-wide trematode species richness associated with P. acuta, and to identify relevant host-population parameters important in modeling host-parasite invasion.

RESULTS: Phylogenetic analyses using mtDNA uncovered two major clades (A & B). Clade A occurs globally while clade B was only recovered from the Western USA. All invasive populations sampled grouped within Clade A, where multiple independent source populations were identified from across North America. Significant population genetic structure was found within the native range of P. acuta, with some evidence for contemporary geographic barriers between western and eastern populations. Mito-nuclear discordance was found suggesting historical isolation with secondary contact between the two mitochondrial clades. Trematode species richness was found to differ significantly between native and invasive populations, in concordance with the 'Enemy-Release hypothesis'. Further, our data suggests a positive relationship between nucleotide diversity of invasive populations and trematode prevalence and richness.

CONCLUSIONS: This study includes a wider geographic sampling of P. acuta within its native range that provides insight into phylogeographic and population genetic structure, range-wide genetic diversity and estimation of the invasion history. Meta-analysis of P. acuta - trematode surveys globally is consistent with the 'Enemy-Release hypothesis'. Additionally, results from this study suggest that host demographic parameters, namely genetic diversity as a proxy for population size, may play an essential role in how parasite communities assemble within invasive host populations. This knowledge can be used to begin to construct a framework to model host-parasite invasion dynamics over time.}, } @article {pmid29969986, year = {2018}, author = {Minchin, RF and Butcher, NJ}, title = {Trimodal distribution of arylamine N-acetyltransferase 1 mRNA in breast cancer tumors: association with overall survival and drug resistance.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {513}, pmid = {29969986}, issn = {1471-2164}, support = {1083036//National Health and Medical Research Council/ ; }, mesh = {Antineoplastic Agents/therapeutic use ; Antineoplastic Agents, Hormonal/therapeutic use ; Arylamine N-Acetyltransferase/*genetics ; Breast Neoplasms/drug therapy/*genetics/mortality/pathology ; Drug Resistance, Neoplasm/*genetics ; Female ; Humans ; Isoenzymes/*genetics ; Kaplan-Meier Estimate ; Proportional Hazards Models ; RNA, Messenger/genetics/metabolism ; Receptors, Estrogen/metabolism ; }, abstract = {BACKGROUND: Arylamine N-acetyltransferase 1 (NAT1) is a drug metabolizing enzyme that has been associated with cancer cell proliferation in vitro and with survival in vivo. NAT1 expression has been associated with the estrogen receptor and it has been proposed as a prognostic marker for estrogen receptor positive cancers. However, little is known about the distribution of NAT1 mRNA across an entire patient population or its effects on outcomes. To address this, gene expression data from breast cancer patient cohorts were investigated to identify sub-populations based on the level of NAT1 expression. Patient survival and drug response was examined to determine whether NAT1 mRNA levels influenced any of these parameters.

RESULTS: NAT1 expression showed a trimodal distribution in breast cancer samples (n = 1980) but not in tumor tissue from ovarian, prostate, cervical or colorectal cancers. In breast cancer, NAT1 mRNA in each sub-population correlated with a separate set of genes suggesting different mechanisms of NAT1 gene regulation. Kaplan-Meier plots showed significantly better survival in patients with highest NAT1 mRNA compared to those with intermediate or low expression. While NAT1 expression was elevated in estrogen receptor-positive patients, it did not appear to be dependent on estrogen receptor expression. Overall survival was analyzed in patients receiving no treatment, hormone therapy or chemotherapy. NAT1 expression correlated strongly with survival in the first 5 years in those patients receiving chemotherapy but did not influence survival in the other two groups. This suggests that low NAT1 expression is associated with chemo-resistance. The sensitivity of NAT1 mRNA levels as a single parameter to identify non-responders to chemotherapy was 0.58 at a log(2) < 6.5.

CONCLUSIONS: NAT1 mRNA can be used to segregate breast cancer patients into sub-populations that demonstrate different overall survival. Moreover, low NAT1 expression shows a distinct poor response to chemotherapy. Analysis of NAT1 expression may be useful for identifying specific individuals who would benefit from alternative therapy or drug combinations. However, additional information is required to increase the sensitivity of identifying non-responders.}, } @article {pmid29969985, year = {2018}, author = {Lima, RPM and Curtolo, M and Merfa, MV and Cristofani-Yaly, M and Machado, MA}, title = {QTLs and eQTLs mapping related to citrandarins' resistance to citrus gummosis disease.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {516}, pmid = {29969985}, issn = {1471-2164}, support = {Fapesp 2014/50880-0 and CNPq 465440/2014-2//INCT Citros/ ; 2011/18605-0//FAPESP/ ; }, mesh = {Chromosome Mapping ; Citrus/*genetics ; Disease Resistance/*genetics ; Host-Parasite Interactions/genetics ; Phenotype ; Phytophthora/genetics/pathogenicity ; Plant Diseases/*genetics/parasitology ; Plant Leaves/genetics ; *Quantitative Trait Loci ; RNA, Plant/isolation & purification/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Phytophthora nicotianae Breda de Haan (Phytophthora parasitica Dastur) causes severe damage to citrus crops worldwide. A population of citrandarins was created from the cross between the susceptible parent Citrus sunki Hort. Ex Tan. and the resistant parent Poncirus trifoliata (L.) Raf. cv. Rubidoux, both parents and two reference rootstocks (Rangpur lime and Swingle citrumelo) were grafted in a greenhouse on Rangpur lime. Inoculations were performed at 10 cm and 15 cm above the grafting region and the resulting lesions were evaluated by measuring the lesion length 60 days after inoculation. As control, non-inoculated plants of each genotype were used. In addition, we evaluated the expression of 19 candidate genes involved in citrus defense response 48 h after pathogen infection by quantitative Real-Time PCR (qPCR). We mapped genomic regions of Quantitative Trait Loci (QTLs) and Expression Quantitative Trait Loci (eQTLs) associated with resistance to P. parasitica in the linkage groups (LGs) of the previously constructed maps of C. sunki and P. trifoliata.

RESULTS: We found disease severity differences among the generated hybrids, with lesion lengths varying from 1.15 to 11.13 mm. The heritability of the character was 65%. These results indicate that there is a great possibility of success in the selection of resistant hybrids within this experiment. The analysis of gene expression profile demonstrated a great variation of responses regarding the activation of plant defense pathways, indicating that citrandarins have several defense strategies to control oomycete infection. The information of the phenotypic and gene expression data made possible to detect genomic regions associated with resistance. Three QTLs and 84 eQTLs were detected in the linkage map of P. trifoliata, while one QTL and 110 eQTLs were detected in C. sunki.

CONCLUSIONS: This is the first study to use eQTLs mapping in the Phytophthora-citrus interaction. Our results from the QTLs and eQTLs mapping allow us to conclude that the resistance of some citrandarins to the infection by P. parasitica is due to a favorable combination of QTLs and eQTLs transmitted by both parents.}, } @article {pmid29969984, year = {2018}, author = {Li, W and Liu, J and Tan, H and Luo, L and Cui, J and Hu, J and Wang, S and Liu, Q and Hu, F and Tang, C and Ren, L and Yang, C and Zhao, R and Tao, M and Zhang, C and Qin, Q and Liu, S}, title = {Asymmetric expression patterns reveal a strong maternal effect and dosage compensation in polyploid hybrid fish.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {517}, pmid = {29969984}, issn = {1471-2164}, support = {31730098//National Natural Science Foundation of China/ ; 31430088//National Natural Science Foundation of China/ ; CARS-45//the earmarked fund for China Agriculture Research System/ ; 20134486//Cooperative Innovation Center of Engineering and New Products for Developmental Biology of Hunan Province/ ; 2017NK1031//Hunan Provincial Natural Science and Technology Major Project/ ; }, mesh = {Animals ; Chimera/*genetics ; Cyprinidae/*genetics ; Dosage Compensation, Genetic/*genetics ; Female ; Male ; Maternal Inheritance/*genetics ; Polyploidy ; RNA/chemistry/isolation & purification/metabolism ; Sequence Analysis, RNA ; Testis/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Hybridization and polyploidization are regarded as the major driving forces in plant speciation, diversification, and ecological adaptation. Our knowledge regarding the mechanisms of duplicated-gene regulation following genomic merging or doubling is primarily derived from plants and is sparse for vertebrates.

RESULTS: We successfully obtained an F1 generation (including allodiploid hybrids and triploid hybrids) from female Megalobrama amblycephala Yih (BSB, 2n = 48) × male Xenocypri davidi Bleeker (YB, 2n = 48). The duplicated-gene expression patterns of the two types of hybrids were explored using RNA-Seq data. In total, 5.44 × 108 (69.32 GB) clean reads and 499,631 assembled unigenes were obtained from the testis transcriptomes. The sequence similarity analysis of 4265 orthologs revealed that the merged genomes were dominantly expressed in different ploidy hybrids. The differentially expressed genes in the two types of hybrids were asymmetric compared with those in both parents. Furthermore, the genome-wide expression level dominance (ELD) was biased toward the maternal BSB genome in both the allodiploid and triploid hybrids. In addition, the dosage-compensation mechanisms that reduced the triploid expression levels to the diploid state were determined in the triploid hybrids.

CONCLUSIONS: Our results indicate that divergent genomes undergo strong interactions and domination in allopolyploid offspring. Genomic merger has a greater effect on the gene-expression patterns than genomic doubling. The various expression mechanisms (including maternal effect and dosage compensation) in different ploidy hybrids suggest that the initial genomic merger and doubling play important roles in polyploidy adaptation and evolution.}, } @article {pmid29969983, year = {2018}, author = {Xie, D and Dai, Z and Yang, Z and Tang, Q and Sun, J and Yang, X and Song, X and Lu, Y and Zhao, D and Zhang, L and Su, J}, title = {Genomic variations and association study of agronomic traits in flax.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {512}, pmid = {29969983}, issn = {1471-2164}, support = {31471546//National Natural Science Foundation of China/ ; 2016M591302//Fund for the 59th Batch of Certificate of China Postdoctoral Science Foundation/ ; CARS-19-E01//China Agriculture Research System/ ; ASTIP-IBFC01//Agriculture Scientific and Technological Innovation Project of Chinese Academy of Agricultural Sciences/ ; 201507-43//Introduction of Doctor's Personnel Scientific Research and Development Fund/ ; C2015031//Project of Heilongjiang Natural Science Foundation of China/ ; }, mesh = {Biological Evolution ; Flax/classification/*genetics ; Gene Flow ; Genetic Variation ; *Genome, Plant ; *Genome-Wide Association Study ; Linkage Disequilibrium ; Phenotype ; Phylogeny ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Flax (Linum usitatissimum. L) is an ancient oilseed and natural fiber crop. It could be divided into three categories by use, namely oil flax, fiber flax and oil-fiber dual purpose (OF). Cultivated flax is widely used in the food and textile industry. It is of great significance to elucidate the genetic characteristics of flax collections for accelerating the process of breeding improvement in this dual purpose crop. With the development of next-generation sequencing, we can use new methods, such as SLAF-seq (specific-locus amplified fragment sequencing), to decode unknown genomes of species. In this study, a high-through sequencing of flax collections using SLAF-seq was conducted. The evolutionary tendency was defined and candidate genes associated with agronomic traits of flax species were identified by Genome-Wide Association Studying (GWAS).

RESULTS: A flax collection consisting of 224 varieties were sequenced by SLAF-seq. In total, 346,639 SLAF tags were developed from all accessions, with an average sequencing depth of 7.19 for each accession. A total of 584,987 SNPs (single nucleotide polymorphism) with an MAF > 0.05 were identified from these SLAFs. The population structure division and phylogenetic analysis indicated a strong divergence among three kinds of flax groups. The genome-wide variation uncovered that oil flax had the highest genetic diversity and was considered to be the ancestor of fiber flax and oil-fiber flax. Sixteen associated peak SNPs for six traits were obtained by GWAS of oil-related traits using EMMAX (efficient mixed-model association eXpedited). Candidate genes and their related pathway were evaluated. A new GWAS was developed for fiber properties using the GLM (General linear model) model and a number of loci were identified.

CONCLUSIONS: To our knowledge, this is the first study on discovery multiple loci for important agronomic traits of flax species using GWAS strategy. These results will provide the highest possibility of incorporating both high fiber and good oil traits in a single variety.}, } @article {pmid29969982, year = {2018}, author = {Barbosa, CS and Fonseca, RRD and Batista, TM and Barreto, MA and Argolo, CS and Carvalho, MR and Amaral, DOJD and Silva, EMA and Arévalo-Gardini, E and Hidalgo, KS and Franco, GR and Pirovani, CP and Micheli, F and Gramacho, KP}, title = {Genome sequence and effectorome of Moniliophthora perniciosa and Moniliophthora roreri subpopulations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {509}, pmid = {29969982}, issn = {1471-2164}, mesh = {Agaricales/classification/*genetics/isolation & purification ; Brazil ; Cacao/microbiology ; DNA, Fungal/chemistry/isolation & purification/metabolism ; Fungal Proteins/genetics ; *Genome, Fungal ; Phylogeny ; Plant Diseases/*microbiology ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: The hemibiotrophic pathogens Moniliophthora perniciosa (witches' broom disease) and Moniliophthora roreri (frosty pod rot disease) are among the most important pathogens of cacao. Moniliophthora perniciosa has a broad host range and infects a variety of meristematic tissues in cacao plants, whereas M. roreri infects only pods of Theobroma and Herrania genera. Comparative pathogenomics of these fungi is essential to understand Moniliophthora infection strategies, therefore the detection and in silico functional characterization of effector candidates are important steps to gain insight on their pathogenicity.

RESULTS: Candidate secreted effector proteins repertoire were predicted using the genomes of five representative isolates of M. perniciosa subpopulations (three from cacao and two from solanaceous hosts), and one representative isolate of M. roreri from Peru. Many putative effectors candidates were identified in M. perniciosa: 157 and 134 in cacao isolates from Bahia, Brazil; 109 in cacao isolate from Ecuador, 92 and 80 in wild solanaceous isolates from Minas Gerais (Lobeira) and Bahia (Caiçara), Brazil; respectively. Moniliophthora roreri showed the highest number of effector candidates, a total of 243. A set of eight core effectors were shared among all Moniliophthora isolates, while others were shared either between the wild solanaceous isolates or among cacao isolates. Mostly, candidate effectors of M. perniciosa were shared among the isolates, whereas in M. roreri nearly 50% were exclusive to the specie. In addition, a large number of cell wall-degrading enzymes characteristic of hemibiotrophic fungi were found. From these, we highlighted the proteins involved in cell wall modification, an enzymatic arsenal that allows the plant pathogens to inhabit environments with oxidative stress, which promotes degradation of plant compounds and facilitates infection.

CONCLUSIONS: The present work reports six genomes and provides a database of the putative effectorome of Moniliophthora, a first step towards the understanding of the functional basis of fungal pathogenicity.}, } @article {pmid29969981, year = {2018}, author = {Sivakumar, TV and Bhaduri, A and Duvvuru Muni, RR and Park, JH and Kim, TY}, title = {SimCAL: a flexible tool to compute biochemical reaction similarity.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {254}, pmid = {29969981}, issn = {1471-2105}, abstract = {BACKGROUND: Computation of reaction similarity is a pre-requisite for several bioinformatics applications including enzyme identification for specific biochemical reactions, enzyme classification and mining for specific inhibitors. Reaction similarity is often assessed at either two levels: (i) comparison across all the constituent substrates and products of a reaction, reaction level similarity, (ii) comparison at the transformation center with various degrees of neighborhood, transformation level similarity. Existing reaction similarity computation tools are designed for specific applications and use different features and similarity measures. A single system integrating these diverse features enables comparison of the impact of different molecular properties on similarity score computation.

RESULTS: To address these requirements, we present SimCAL, an integrated system to calculate reaction similarity with novel features and capability to perform comparative assessment. SimCAL provides reaction similarity computation at both whole reaction level and transformation level. Novel physicochemical features such as stereochemistry, mass, volume and charge are included in computing reaction fingerprint. Users can choose from four different fingerprint types and nine molecular similarity measures. Further, a comparative assessment of these features is also enabled. The performance of SimCAL is assessed on 3,688,122 reaction pairs with Enzyme Commission (EC) number from MetaCyc and achieved an area under the curve (AUC) of > 0.9. In addition, SimCAL results showed strong correlation with state-of-the-art EC-BLAST and molecular signature based reaction similarity methods.

CONCLUSIONS: SimCAL is developed in java and is available as a standalone tool, with intuitive, user-friendly graphical interface and also as a console application. With its customizable feature selection and similarity calculations, it is expected to cater a wide audience interested in studying and analyzing biochemical reactions and metabolic networks.}, } @article {pmid29969980, year = {2018}, author = {Phillips, MJ and Fruciano, C}, title = {The soft explosive model of placental mammal evolution.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {104}, pmid = {29969980}, issn = {1471-2148}, support = {DP150104659//Australian Research Council/International ; }, mesh = {Animals ; Biodiversity ; *Biological Evolution ; Calibration ; Computer Simulation ; Eutheria/*physiology ; Female ; Fossils ; *Models, Biological ; Phylogeny ; Pregnancy ; Time Factors ; }, abstract = {BACKGROUND: Recent molecular dating estimates for placental mammals echo fossil inferences for an explosive interordinal diversification, but typically place this event some 10-20 million years earlier than the Paleocene fossils, among apparently more "primitive" mammal faunas.

RESULTS: However, current models of molecular evolution do not adequately account for parallel rate changes, and result in dramatic divergence underestimates for large, long-lived mammals such as whales and hominids. Calibrating among these taxa shifts the rate model errors deeper in the tree, inflating interordinal divergence estimates. We employ simulations based on empirical rate variation, which show that this "error-shift inflation" can explain previous molecular dating overestimates relative to fossil inferences. Molecular dating accuracy is substantially improved in the simulations by focusing on calibrations for taxa that retain plesiomorphic life-history characteristics. Applying this strategy to the empirical data favours the soft explosive model of placental evolution, in line with traditional palaeontological interpretations - a few Cretaceous placental lineages give rise to a rapid interordinal diversification following the 66 Ma Cretaceous-Paleogene boundary mass extinction.

CONCLUSIONS: Our soft explosive model for the diversification of placental mammals brings into agreement previously incongruous molecular, fossil, and ancestral life history estimates, and closely aligns with a growing consensus for a similar model for bird evolution. We show that recent criticism of the soft explosive model relies on ignoring both experimental controls and statistical confidence, as well as misrepresentation, and inconsistent interpretations of morphological phylogeny. More generally, we suggest that the evolutionary properties of adaptive radiations may leave current molecular dating methods susceptible to overestimating the timing of major diversification events.}, } @article {pmid29969657, year = {2018}, author = {Martins, AC and Bochorny, T and Pérez-Escobar, OA and Chomicki, G and Monteiro, SHN and de Camargo Smidt, E}, title = {From tree tops to the ground: Reversals to terrestrial habit in Galeandra orchids (Epidendroideae: Catasetinae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {952-960}, doi = {10.1016/j.ympev.2018.06.041}, pmid = {29969657}, issn = {1095-9513}, abstract = {The colonization of the epiphytic niche of Neotropical forest canopies played an important role in orchid's extraordinary diversification, with rare reversions to the terrestrial habit. To understand the evolutionary context of those reversals, we investigated the diversification of Galeandra, a Neotropical orchid genus which includes epiphytic and terrestrial species. We hypothesized that reversion to the terrestrial habit accompanied the expansion of savannas. To test this hypothesis we generated a comprehensive time-calibrated phylogeny and employed comparative methods. We found that Galeandra originated towards the end of the Miocene in Amazonia. The terrestrial clade originated synchronously with the rise of dry vegetation biomes in the last 5 million years, suggesting that aridification dramatically impacted plant diversification and habits in the Neotropics. Shifts in habit impacted floral spur lengths and geographic range size, but not climatic niche. The longer spurs and narrower ranges characterize epiphytic species, which probably adapted to specialized long-tongued Euglossini bee pollinators inhabiting forested habits. The terrestrial species present variable floral spurs and wider distribution ranges, with evidence of self-pollination, suggesting the loss of specialized pollination system and concomitant range expansion. Our study highlights how climate change impacted habit evolution and associated traits such as mutualistic interactions with pollinators.}, } @article {pmid29969656, year = {2018}, author = {Evangelista, D and Thouzé, F and Kohli, MK and Lopez, P and Legendre, F}, title = {Topological support and data quality can only be assessed through multiple tests in reviewing Blattodea phylogeny.}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {112-122}, doi = {10.1016/j.ympev.2018.05.007}, pmid = {29969656}, issn = {1095-9513}, abstract = {Assessing support for molecular phylogenies is difficult because the data is heterogeneous in quality and overwhelming in quantity. Traditionally, node support values (bootstrap frequency, Bayesian posterior probability) are used to assess confidence in tree topologies. Other analyses to assess the quality of phylogenetic data (e.g. Lento plots, saturation plots, trait consistency) and the resulting phylogenetic trees (e.g. internode certainty, parameter permutation tests, topological tests) exist but are rarely applied. Here we argue that a single qualitative analysis is insufficient to assess support of a phylogenetic hypothesis and relate data quality to tree quality. We use six molecular markers to infer the phylogeny of Blattodea and apply various tests to assess relationship support, locus quality, and the relationship between the two. We use internode-certainty calculations in conjunction with bootstrap scores, alignment permutations, and an approximately unbiased (AU) test to assess if the molecular data unambiguously support the phylogenetic relationships found. Our results show higher support for the position of Lamproblattidae, high support for the termite phylogeny, and low support for the position of Anaplectidae, Corydioidea and phylogeny of Blaberoidea. We use Lento plots in conjunction with mutation-saturation plots, calculations of locus homoplasy to assess locus quality, identify long branch attraction, and decide if the tree's relationships are the result of data biases. We conclude that multiple tests and metrics need to be taken into account to assess tree support and data robustness.}, } @article {pmid29969090, year = {2018}, author = {Castro, JF and Nouioui, I and Sangal, V and Choi, S and Yang, SJ and Kim, BY and Trujillo, ME and Riesco, R and Montero-Calasanz, MDC and Rahmani, TPD and Bull, AT and Sutcliffe, IC and Asenjo, JA and Andrews, B and Goodfellow, M}, title = {Blastococcus atacamensis sp. nov., a novel strain adapted to life in the Yungay core region of the Atacama Desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {9}, pages = {2712-2721}, doi = {10.1099/ijsem.0.002828}, pmid = {29969090}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Chile ; DNA, Bacterial/genetics ; *Desert Climate ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A polyphasic study was undertaken to establish the taxonomic status of a Blastococcus strain isolated from an extreme hyper-arid Atacama Desert soil. The isolate, strain P6T, was found to have chemotaxonomic and morphological properties consistent with its classification in the genus Blastococcus. It was shown to form a well-supported branch in the Blastococcus 16S rRNA gene tree together with the type strains of Blastococcus capsensis and Blastococcus saxobsidens and was distinguished from the latter, its close phylogenetic neighbour, by a broad range of phenotypic properties. The draft genome sequence of isolate P6T showed 84.6 % average nucleotide identity, 83.0 % average amino acid identity and a digital DNA-DNA hybridisation value of 27.8 % in comparison with the genome sequence of B. saxobsidens DSM 44509T, values consistent with its assignment to a separate species. Based on these data it is proposed that isolate P6T (NCIMB 15090T=NRRL B-65468T) be assigned to the genus Blastococcus as Blastococcus atacamensis sp. nov. Analysis of the whole genome sequence of B. atacamensis P6T, with 3778 open reading frames and a genome size of 3.9 Mb showed the presence of genes and gene clusters that encode for properties that reflect its adaptation to the extreme environmental conditions that prevail in Atacama Desert soils.}, } @article {pmid29969086, year = {2018}, author = {Li, L and Li, YQ and Fu, YS and Zhang, H and Alkhalifah, DHM and Salam, N and Hozzein, WN and Asem, MD and Li, WJ}, title = {Nesterenkonia endophytica sp. nov., isolated from roots of Glycyrrhiza uralensis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2659-2663}, doi = {10.1099/ijsem.0.002905}, pmid = {29969086}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Glycyrrhiza uralensis/*microbiology ; Micrococcaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {A Gram-positive and non-motile actinobacterium, designated strain EGI 60016T, was isolated from healthy roots of Glycyrrhiza uralensis F. collected from Xinyuan County, Xinjiang Province, China. The 16S rRNA gene sequence of strain EGI 60016T was found to show 97.5 and 97.3 % sequence similarities to Nesterenkonia rhizosphaerae EGI 80099T and Nesternkonia massiliensis NP1T, respectively. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain EGI 60016T formed a distinct clade with N. rhizosphaerae EGI 80099T and N. massiliensis NP1T. The polar lipids detected for strain EGI 60016T were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol, an unidentified glycolipid, an unidentified lipid and an unidentified phospholipid. The DNA G+C content was determined to be 64.1 mol%. Other chemotaxonomic features of strain EGI 60016T included MK-7, MK-8 and MK-9 as the respiratory quinones, and anteiso-C15 : 0 and anteiso-C17 : 0 as the major fatty acids. Based on the results of the phylogenetic analysis supported by morphological, physiological, chemotaxonomic and other differentiating phenotypic characteristics, strain EGI 60016T is considered to represent a novel species of the genus Nesterenkonia, for which the name Nesterenkonia endophytica sp. nov. is proposed. The type strain is EGI 60016T (=CCTCC AB 2017176T=NBRC 112398T).}, } @article {pmid29968844, year = {2018}, author = {Skipper, M}, title = {A welcome from the new Nature editor.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {6}, doi = {10.1038/d41586-018-05606-y}, pmid = {29968844}, issn = {1476-4687}, } @article {pmid29968843, year = {2018}, author = {Dunne, CP and Dunne, SS}, title = {Personalized medicine should not be restricted to the wealthy.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {32}, doi = {10.1038/d41586-018-05609-9}, pmid = {29968843}, issn = {1476-4687}, mesh = {Facilities and Services Utilization/*economics/*trends ; Healthcare Disparities/*economics/trends ; Humans ; Orphan Drug Production/economics ; Precision Medicine/*economics/*trends ; *Social Class ; }, } @article {pmid29968842, year = {2018}, author = {Caminiti, R}, title = {University came to the rescue of accused researcher.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {32}, doi = {10.1038/d41586-018-05611-1}, pmid = {29968842}, issn = {1476-4687}, mesh = {Animal Rights ; Animals ; *Research Personnel ; *Universities ; }, } @article {pmid29968841, year = {2018}, author = {Hatch, A and Curry, S}, title = {Evaluation woes: we're on it, responds DORA.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {32}, doi = {10.1038/d41586-018-05596-x}, pmid = {29968841}, issn = {1476-4687}, mesh = {*Journal Impact Factor ; *Publishing ; }, } @article {pmid29968840, year = {2018}, author = {Zannoni, D}, title = {Italy is squeezing out wet biology research.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {32}, doi = {10.1038/d41586-018-05610-2}, pmid = {29968840}, issn = {1476-4687}, } @article {pmid29968839, year = {2018}, author = {Freeman, J}, title = {LGBTQ scientists are still left out.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {27-28}, doi = {10.1038/d41586-018-05587-y}, pmid = {29968839}, issn = {1476-4687}, mesh = {Homophobia/*statistics & numerical data ; *Research ; Research Personnel/psychology/*statistics & numerical data ; Sexual and Gender Minorities/psychology/*statistics & numerical data ; Workforce ; }, } @article {pmid29968838, year = {2018}, author = {Nowogrodzki, A}, title = {Speaking in code: how to program by voice.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {141-142}, doi = {10.1038/d41586-018-05588-x}, pmid = {29968838}, issn = {1476-4687}, mesh = {*Computers ; Cumulative Trauma Disorders/*rehabilitation ; *Equipment and Supplies Utilization/economics ; Female ; Humans ; Male ; Natural Language Processing ; Small Fiber Neuropathy/rehabilitation ; *Speech Recognition Software/economics ; }, } @article {pmid29968837, year = {2018}, author = {Will, CM}, title = {General relativity verified by a triple-star system.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {40-41}, doi = {10.1038/d41586-018-05549-4}, pmid = {29968837}, issn = {1476-4687}, } @article {pmid29968836, year = {2018}, author = {Kirby, E}, title = {Doubt cast on how the pace of global glacial erosion responds to climate cooling.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {34-35}, doi = {10.1038/d41586-018-05563-6}, pmid = {29968836}, issn = {1476-4687}, } @article {pmid29968835, year = {2018}, author = {Harrington, K}, title = {Harness the power of groups to beat the 'PhD blues'.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {143-144}, doi = {10.1038/d41586-018-05589-w}, pmid = {29968835}, issn = {1476-4687}, mesh = {*Adaptation, Psychological ; Confidentiality ; Depression/*prevention & control ; *Education, Graduate ; Efficiency ; Goals ; Group Processes ; Humans ; Mentoring ; Motivation ; *Peer Group ; Respect ; Social Isolation ; *Social Networking ; Students/*psychology ; Trust ; Victoria ; Work-Life Balance ; *Writing ; }, } @article {pmid29968834, year = {2018}, author = {}, title = {50 & 100 years ago.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {39}, doi = {10.1038/d41586-018-05594-z}, pmid = {29968834}, issn = {1476-4687}, } @article {pmid29968833, year = {2018}, author = {Cyranoski, D}, title = {Gigantic study of Chinese babies yields slew of health data.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {13-14}, doi = {10.1038/d41586-018-05522-1}, pmid = {29968833}, issn = {1476-4687}, mesh = {*Asian Continental Ancestry Group ; *Cohort Studies ; Humans ; Statistics as Topic ; }, } @article {pmid29968832, year = {2018}, author = {}, title = {Mars's river valleys whisper of a rainy past.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {9}, doi = {10.1038/d41586-018-05553-8}, pmid = {29968832}, issn = {1476-4687}, } @article {pmid29968831, year = {2018}, author = {Dolgin, E}, title = {There's no limit to longevity, says study that revives human lifespan debate.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {14-15}, doi = {10.1038/d41586-018-05582-3}, pmid = {29968831}, issn = {1476-4687}, mesh = {Humans ; *Longevity ; }, } @article {pmid29968830, year = {2018}, author = {}, title = {Consumers soften to genetically engineered foods after addition of labels.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {8-9}, doi = {10.1038/d41586-018-05572-5}, pmid = {29968830}, issn = {1476-4687}, } @article {pmid29968829, year = {2018}, author = {Witze, A}, title = {Delays mount for NASA's $8-billion Hubble successor.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {16-17}, doi = {10.1038/d41586-018-05567-2}, pmid = {29968829}, issn = {1476-4687}, } @article {pmid29968828, year = {2018}, author = {}, title = {Brain-protein structure could point way to safer prescription drugs.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {5}, doi = {10.1038/d41586-018-05578-z}, pmid = {29968828}, issn = {1476-4687}, mesh = {Brain ; *Drug Prescriptions ; *Prescription Drugs ; }, } @article {pmid29968827, year = {2018}, author = {Makri, A}, title = {Cyprus asserts itself as regional hub for climate-change research.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {15-16}, doi = {10.1038/d41586-018-05528-9}, pmid = {29968827}, issn = {1476-4687}, mesh = {Academies and Institutes/*organization & administration ; *Climate Change ; Cyprus ; European Union ; Global Warming/prevention & control ; Mediterranean Region ; Middle East ; Research/*organization & administration/statistics & numerical data/trends ; }, } @article {pmid29968826, year = {2018}, author = {}, title = {Molecular fog cooled to 40 millionths of a degree.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {9}, doi = {10.1038/d41586-018-05547-6}, pmid = {29968826}, issn = {1476-4687}, } @article {pmid29968825, year = {2018}, author = {}, title = {CRISPR with a heart of gold helps ailing mice.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {8}, doi = {10.1038/d41586-018-05545-8}, pmid = {29968825}, issn = {1476-4687}, } @article {pmid29968824, year = {2018}, author = {}, title = {First known haven for baby rays found off Texas coast.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {8}, doi = {10.1038/d41586-018-05539-6}, pmid = {29968824}, issn = {1476-4687}, } @article {pmid29968823, year = {2018}, author = {}, title = {Mouse embryos' balancing act revealed.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {9}, doi = {10.1038/d41586-018-05540-z}, pmid = {29968823}, issn = {1476-4687}, } @article {pmid29968822, year = {2018}, author = {}, title = {'Eyes in the sky' spot hidden threat to Italy's olive trees.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {8}, doi = {10.1038/d41586-018-05530-1}, pmid = {29968822}, issn = {1476-4687}, } @article {pmid29968821, year = {2018}, author = {}, title = {Unravelling the physics of knitting.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {9}, doi = {10.1038/d41586-018-05542-x}, pmid = {29968821}, issn = {1476-4687}, } @article {pmid29968820, year = {2018}, author = {}, title = {To make plastic, just add blood.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {9}, doi = {10.1038/d41586-018-05537-8}, pmid = {29968820}, issn = {1476-4687}, } @article {pmid29968383, year = {2018}, author = {Xie, N and Sen, B and Song, Z and Zhao, Y and Chen, Z and Shi, W and Zhang, Y and Zhang, J and Johnson, ZI and Wang, G}, title = {High phylogenetic diversity and abundance pattern of Labyrinthulomycete protists in the coastal waters of the Bohai Sea.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3042-3056}, doi = {10.1111/1462-2920.14341}, pmid = {29968383}, issn = {1462-2920}, support = {31670044, 91751115 and 31602185//National Science Foundation of China/ ; 2016YFA0601401//National Key R&D Program/ ; }, abstract = {The unicellular Labyrinthulomycete protists have long been considered to play a significant role in ocean carbon cycling. However, their distribution and biogeochemical function remain poorly understood. We present a large-scale study of their spatiotemporal abundance and diversity in the coastal waters of Bohai Sea using flow cytometry and high-throughput sequencing. These protists display niche preferences and episodic higher biomass than that of bacterioplankton with much phylogenetic diversity (> 4000 OTUs) ever reported. They were ubiquitous with a typical abundance range of 100-1000 cells ml-1 and biomass range of 0.06-574.59 μg C L-1 . The observed spatiotemporal abundance variations support the current 'left-over scavengers' nutritional model and highlight these protists as a significant component of the marine microbial loop. The higher average abundance and phylogenetic diversity in the nearshore compared with those in the offshore reveal their predominant role in the terrigenous matter decomposition. Furthermore, the differential relationship of the protist genera to environmental conditions together with their co-occurrence network suggests their unique substrate preferences and niche partitioning. With few subnetworks and possible keystone species, their network topology indicates community resilience and high connectance level of few operational taxonomic units (OTUs). We demonstrate the significant contribution of these protists to the secondary production and nutrient cycling in the coastal waters. As secondary producers, their role will become more important with increasingly coastal eutrophication.}, } @article {pmid29968367, year = {2018}, author = {Dekas, AE and Fike, DA and Chadwick, GL and Green-Saxena, A and Fortney, J and Connon, SA and Dawson, KS and Orphan, VJ}, title = {Widespread nitrogen fixation in sediments from diverse deep-sea sites of elevated carbon loading.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4281-4296}, doi = {10.1111/1462-2920.14342}, pmid = {29968367}, issn = {1462-2920}, support = {3780//Gordon and Betty Moore Foundation (GBMF)/ ; //US Department of Energy/ ; //Office of Science/ ; DE-SC0003940//Office of Biological and Environmental Research/ ; DE-SC0004949//Office of Biological and Environmental Research/ ; MCB-0348492//National Science Foundation/ ; OCE-1634297//National Science Foundation/ ; }, abstract = {Nitrogen fixation, the biological conversion of N2 to NH3 , is critical to alleviating nitrogen limitation in many marine ecosystems. To date, few measurements exist of N2 fixation in deep-sea sediments. Here, we conducted > 400 bottle incubations with sediments from methane seeps, whale falls and background sites off the western coast of the United States from 600 to 2893 m water depth to investigate the potential rates, spatial distribution and biological mediators of benthic N2 fixation. We found that N2 fixation was widespread, yet heterogeneously distributed with sediment depth at all sites. In some locations, rates exceeded previous measurements by > 10×, and provided up to 30% of the community anabolic growth requirement for nitrogen. Diazotrophic activity appeared to be inhibited by pore water ammonium: N2 fixation was only observed if incubation ammonium concentrations were ≤ 25 μM, and experimental additions of ammonium reduced diazotrophy. In seep sediments, N2 fixation was dependent on CH4 and coincident with sulphate reduction, consistent with previous work showing diazotrophy by microorganisms mediating sulphate-coupled methane oxidation. However, the pattern of diazotrophy was different in whale-fall and associated reference sediments, where it was largely unaffected by CH4 , suggesting catabolically different diazotrophs at these sites.}, } @article {pmid29968357, year = {2018}, author = {Vuillemin, A and Horn, F and Friese, A and Winkel, M and Alawi, M and Wagner, D and Henny, C and Orsi, WD and Crowe, SA and Kallmeyer, J}, title = {Metabolic potential of microbial communities from ferruginous sediments.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4297-4313}, doi = {10.1111/1462-2920.14343}, pmid = {29968357}, issn = {1462-2920}, support = {0487//NSERC/ ; P2GEP2_148621//Swiss National Science Foundation/ ; //University of Geneva/ ; KA 2293/8-1//Deutsche Forschungsgemeinschaft/ ; VU 94/1-1//Deutsche Forschungsgemeinschaft/ ; OR 417/1-1//Deutsche Forschungsgemeinschaft/ ; }, abstract = {Ferruginous (Fe-rich, SO4 -poor) conditions are generally restricted to freshwater sediments on Earth today, but were likely widespread during the Archean and Proterozoic Eons. Lake Towuti, Indonesia, is a large ferruginous lake that likely hosts geochemical processes analogous to those that operated in the ferruginous Archean ocean. The metabolic potential of microbial communities and related biogeochemical cycling under such conditions remain largely unknown. We combined geochemical measurements (pore water chemistry, sulfate reduction rates) with metagenomics to link metabolic potential with geochemical processes in the upper 50 cm of sediment. Microbial diversity and quantities of genes for dissimilatory sulfate reduction (dsrAB) and methanogenesis (mcrA) decrease with increasing depth, as do rates of potential sulfate reduction. The presence of taxa affiliated with known iron- and sulfate-reducers implies potential use of ferric iron and sulfate as electron acceptors. Pore-water concentrations of acetate imply active production through fermentation. Fermentation likely provides substrates for respiration with iron and sulfate as electron donors and for methanogens that were detected throughout the core. The presence of ANME-1 16S and mcrA genes suggests potential for anaerobic methane oxidation. Overall our data suggest that microbial community metabolism in anoxic ferruginous sediments support coupled Fe, S and C biogeochemical cycling.}, } @article {pmid29968336, year = {2018}, author = {Vorobev, A and Sharma, S and Yu, M and Lee, J and Washington, BJ and Whitman, WB and Ballantyne, F and Medeiros, PM and Moran, MA}, title = {Identifying labile DOM components in a coastal ocean through depleted bacterial transcripts and chemical signals.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3012-3030}, doi = {10.1111/1462-2920.14344}, pmid = {29968336}, issn = {1462-2920}, support = {DMR-1157490//National Science Foundation/ ; //State of Florida/ ; //Roger Nilsen at the Georgia Genomics and Bioinformatics Core/ ; //University of Georgia's Georgia Advanced Computing Resource Centre/ ; OCE-1356010//NSF/ ; OCE-1237140//NSF/ ; IOS-1656311//NSF/ ; 5503//Gordon and Betty Moore Foundation/ ; }, abstract = {Understanding which compounds comprising the complex and dynamic marine dissolved organic matter (DOM) pool are important in supporting heterotrophic bacterial production remains a major challenge. We eliminated sources of labile phytoplankton products, advected terrestrial material and photodegradation products to coastal microbial communities by enclosing water samples in situ for 24 h in the dark. Bacterial genes for which expression decreased between the beginning and end of the incubation and chemical formulae that were depleted over this same time frame were used as indicators of bioavailable compounds, an approach that avoids augmenting or modifying the natural DOM pool. Transport- and metabolism-related genes whose relative expression decreased implicated osmolytes, carboxylic acids, fatty acids, sugars and organic sulfur compounds as candidate bioreactive molecules. FT-ICR MS analysis of depleted molecular formulae implicated functional groups ~ 30-40 Da in size cleaved from semi-polar components of DOM as bioreactive components. Both gene expression and FT-ICR MS analyses indicated higher lability of compounds with sulfur and nitrogen heteroatoms. Untargeted methodologies able to integrate biological and chemical perspectives can be effective strategies for characterizing the labile microbial metabolites participating in carbon flux.}, } @article {pmid29968310, year = {2018}, author = {de Jong, AEE and In 't Zandt, MH and Meisel, OH and Jetten, MSM and Dean, JF and Rasigraf, O and Welte, CU}, title = {Increases in temperature and nutrient availability positively affect methane-cycling microorganisms in Arctic thermokarst lake sediments.}, journal = {Environmental microbiology}, volume = {20}, number = {12}, pages = {4314-4327}, doi = {10.1111/1462-2920.14345}, pmid = {29968310}, issn = {1462-2920}, support = {339880//H2020 European Research Council/ ; 024.002.001024.002.002//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; }, abstract = {Arctic permafrost soils store large amounts of organic matter that is sensitive to temperature increases and subsequent microbial degradation to methane (CH 4) and carbon dioxide (CO 2). Here, we studied methanogenic and methanotrophic activity and community composition in thermokarst lake sediments from Utqiag˙vik (formerly Barrow), Alaska. This experiment was carried out under in situ temperature conditions (4°C) and the IPCC 2013 Arctic climate change scenario (10°C) after addition of methanogenic and methanotrophic substrates for nearly a year. Trimethylamine (TMA) amendment with warming showed highest maximum CH 4 production rates, being 30% higher at 10°C than at 4°C. Maximum methanotrophic rates increased by up to 57% at 10°C compared to 4°C. 16S rRNA gene sequencing indicated high relative abundance of Methanosarcinaceae in TMA amended incubations, and for methanotrophic incubations Methylococcaeae were highly enriched. Anaerobic methanotrophic activity with nitrite or nitrate as electron acceptor was not detected. This study indicates that the methane cycling microbial community can adapt to temperature increases and that their activity is highly dependent on substrate availability.}, } @article {pmid29968288, year = {2018}, author = {Dellero, Y and Rose, S and Metton, C and Morabito, C and Lupette, J and Jouhet, J and Maréchal, E and Rébeillé, F and Amato, A}, title = {Ecophysiology and lipid dynamics of a eukaryotic mangrove decomposer.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {3057-3068}, doi = {10.1111/1462-2920.14346}, pmid = {29968288}, issn = {1462-2920}, support = {ANR-11-BTBR-0008//Océanomics/ ; ANR-10-LABEX-04//GRAL Labex/ ; //French National Research Agency/ ; }, abstract = {Aurantiochytrium limacinum is an osmo-heterotrophic Stramenopile and a pioneering mangrove decomposer which is taxonomically assigned to the family of Thraustochytriaceae (class: Labyrinthulomycetes). The life cycle of A. limacinum involves different cell types including mono- and multi-nucleated cells as well as flagellated zoospores which colonize new fallen leaves. The ecological relevance of thraustochytrids is underestimated and eclipsed by their biotechnological importance, due to their ability to accumulate large amount of lipids, mainly triacylglycerols (TAGs). In this study, we aimed to understand the ecophysiological parameters that trigger zoospore production and the interplay between the life cycle of A. limacinum and its lipid metabolism. When grown in a rich medium, cells accumulated large amounts of TAGs at the end of their growth period, but no zoospores were produced. In poor media such as artificial sea water, zoospores were produced in massive quantities. In the absence of organic carbon, the zoospores remained swimming for at least 6 days, consuming their TAGs in the process. Addition of glucose rapidly triggered the maturation of the zoospores. On the basis of these data, we propose a life cycle for A. limacinum integrating the potential perturbations/changes in the environment surrounding a mangrove leaf that could lead to the production of zoospores and colonization of new areas.}, } @article {pmid29968275, year = {2018}, author = {Morinaga, K and Yamamoto, T and Nomura, N and Toyofuku, M}, title = {Paracoccus denitrificans can utilize various long-chain N-acyl homoserine lactones and sequester them in membrane vesicles.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {651-654}, doi = {10.1111/1758-2229.12674}, pmid = {29968275}, issn = {1758-2229}, abstract = {Many gram-negative bacteria utilize N-acyl homoserine lactone (AHL) signals to communicate with each other. Once they have been released, these signals are assumed to be shared among the population in the local environment. In contrast to this canonical quorum-sensing (QS) model, recent study in Paracoccus denitrificans showed that they can traffic their signals to each other via membrane vesicles (MVs). Here, we demonstrate that various long-chain AHLs inhibited cell aggregation in P. denitrificans, whereas the short-chain AHLs alone did not. Furthermore, MVs released from P. denitrificans were able to take up the long-chain AHLs from the environment into MVs. The AHLs associated with MVs triggered gene expression in P. denitrificans, indicating their role in QS. Our results suggest that P. denitrificans can sequester the AHL produced by other bacteria and deliver the signals to themselves via MVs. Utilizing the signals from other bacteria may be advantageous for P. denitrificans to reach the threshold QS concentration in a polymicrobial community in which the population of its own species is relatively low.}, } @article {pmid29967546, year = {2018}, author = {Cramwinckel, MJ and Huber, M and Kocken, IJ and Agnini, C and Bijl, PK and Bohaty, SM and Frieling, J and Goldner, A and Hilgen, FJ and Kip, EL and Peterse, F and van der Ploeg, R and Röhl, U and Schouten, S and Sluijs, A}, title = {Synchronous tropical and polar temperature evolution in the Eocene.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {382-386}, doi = {10.1038/s41586-018-0272-2}, pmid = {29967546}, issn = {1476-4687}, abstract = {Palaeoclimate reconstructions of periods with warm climates and high atmospheric CO2 concentrations are crucial for developing better projections of future climate change. Deep-ocean1,2 and high-latitude3 palaeotemperature proxies demonstrate that the Eocene epoch (56 to 34 million years ago) encompasses the warmest interval of the past 66 million years, followed by cooling towards the eventual establishment of ice caps on Antarctica. Eocene polar warmth is well established, so the main obstacle in quantifying the evolution of key climate parameters, such as global average temperature change and its polar amplification, is the lack of continuous high-quality tropical temperature reconstructions. Here we present a continuous Eocene equatorial sea surface temperature record, based on biomarker palaeothermometry applied on Atlantic Ocean sediments. We combine this record with the sparse existing data4-6 to construct a 26-million-year multi-proxy, multi-site stack of Eocene tropical climate evolution. We find that tropical and deep-ocean temperatures changed in parallel, under the influence of both long-term climate trends and short-lived events. This is consistent with the hypothesis that greenhouse gas forcing7,8, rather than changes in ocean circulation9,10, was the main driver of Eocene climate. Moreover, we observe a strong linear relationship between tropical and deep-ocean temperatures, which implies a constant polar amplification factor throughout the generally ice-free Eocene. Quantitative comparison with fully coupled climate model simulations indicates that global average temperatures were about 29, 26, 23 and 19 degrees Celsius in the early, early middle, late middle and late Eocene, respectively, compared to the preindustrial temperature of 14.4 degrees Celsius. Finally, combining proxy- and model-based temperature estimates with available CO2 reconstructions8 yields estimates of an Eocene Earth system sensitivity of 0.9 to 2.3 kelvin per watt per square metre at 68 per cent probability, consistent with the high end of previous estimates11.}, } @article {pmid29967492, year = {2018}, author = {Strzyz, P}, title = {Breakdancing on actin.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {469}, doi = {10.1038/s41576-018-0033-y}, pmid = {29967492}, issn = {1471-0064}, } @article {pmid29967487, year = {2018}, author = {Magid, K and Chatterton, RT and Ahamed, FU and Bentley, GR}, title = {Author Correction: Childhood ecology influences salivary testosterone, pubertal age and stature of Bangladeshi UK migrant men.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1331}, doi = {10.1038/s41559-018-0620-5}, pmid = {29967487}, issn = {2397-334X}, abstract = {In the version of this Article originally published, the units for the 'Weight' column in Table 1 were incorrect; they should have been kg. This has now been corrected.}, } @article {pmid29967486, year = {2018}, author = {Jarman, SN and Berry, O and Bunce, M}, title = {The value of environmental DNA biobanking for long-term biomonitoring.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1192-1193}, doi = {10.1038/s41559-018-0614-3}, pmid = {29967486}, issn = {2397-334X}, } @article {pmid29967485, year = {2018}, author = {Venkat, A and Hahn, MW and Thornton, JW}, title = {Multinucleotide mutations cause false inferences of lineage-specific positive selection.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1280-1288}, pmid = {29967485}, issn = {2397-334X}, support = {R01 GM104397/GM/NIGMS NIH HHS/United States ; R01 GM121931/GM/NIGMS NIH HHS/United States ; }, abstract = {Phylogenetic tests of adaptive evolution, such as the widely used branch-site test (BST), assume that nucleotide substitutions occur singly and independently. Recent research has shown that errors at adjacent sites often occur during DNA replication, and the resulting multinucleotide mutations (MNMs) are overwhelmingly likely to be non-synonymous. To evaluate whether the BST misinterprets sequence patterns produced by MNMs as false support for positive selection, we analysed two genome-scale datasets-one from mammals and one from flies. We found that codons with multiple differences account for virtually all the support for lineage-specific positive selection in the BST. Simulations under conditions derived from these alignments but without positive selection show that realistic rates of MNMs cause a strong and systematic bias towards false inferences of selection. This bias is sufficient under empirically derived conditions to produce false positive inferences as often as the BST infers positive selection from the empirical data. Although some genes with BST-positive results may have evolved adaptively, the test cannot distinguish sequence patterns produced by authentic positive selection from those caused by neutral fixation of MNMs. Many published inferences of adaptive evolution using this technique may therefore be artefacts of model violation caused by unincorporated neutral mutational processes. We introduce a model that incorporates MNMs and may help to ameliorate this bias.}, } @article {pmid29967484, year = {2018}, author = {Xiang, H and Liu, X and Li, M and Zhu, Y and Wang, L and Cui, Y and Liu, L and Fang, G and Qian, H and Xu, A and Wang, W and Zhan, S}, title = {The evolutionary road from wild moth to domestic silkworm.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1268-1279}, doi = {10.1038/s41559-018-0593-4}, pmid = {29967484}, issn = {2397-334X}, abstract = {The Silk Road, which derives its name from the trade of silk produced by the domestic silkworm Bombyx mori, was an important episode in the development and interaction of human civilizations. However, the detailed history behind silkworm domestication remains ambiguous, and little is known about the underlying genetics with respect to important aspects of its domestication. Here, we reconstruct the domestication processes and identify selective sweeps by sequencing 137 representative silkworm strains. The results present an evolutionary scenario in which silkworms may have been initially domesticated in China as trimoulting lines, then subjected to independent spreads along the Silk Road that gave rise to the development of most local strains, and further improved for modern silk production in Japan and China, having descended from diverse ancestral sources. We find that genes with key roles in nitrogen and amino acid metabolism may have contributed to the promotion of silk production, and that circadian-related genes are generally selected for their adaptation. We additionally identify associations between several candidate genes and important breeding traits, thereby advancing the applicable value of our resources.}, } @article {pmid29967445, year = {2018}, author = {Verbanck, M and Chen, CY and Neale, B and Do, R}, title = {Publisher Correction: Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1196}, doi = {10.1038/s41588-018-0164-2}, pmid = {29967445}, issn = {1546-1718}, abstract = {In the version of this article initially published, the Supplementary Text and Figures file was missing Supplementary Tables 4, 6, 8 and 10-14. The correct file has now been provided online.}, } @article {pmid29967444, year = {2018}, author = {Johnson, RN and O'Meally, D and Chen, Z and Etherington, GJ and Ho, SYW and Nash, WJ and Grueber, CE and Cheng, Y and Whittington, CM and Dennison, S and Peel, E and Haerty, W and O'Neill, RJ and Colgan, D and Russell, TL and Alquezar-Planas, DE and Attenbrow, V and Bragg, JG and Brandies, PA and Chong, AY and Deakin, JE and Di Palma, F and Duda, Z and Eldridge, MDB and Ewart, KM and Hogg, CJ and Frankham, GJ and Georges, A and Gillett, AK and Govendir, M and Greenwood, AD and Hayakawa, T and Helgen, KM and Hobbs, M and Holleley, CE and Heider, TN and Jones, EA and King, A and Madden, D and Graves, JAM and Morris, KM and Neaves, LE and Patel, HR and Polkinghorne, A and Renfree, MB and Robin, C and Salinas, R and Tsangaras, K and Waters, PD and Waters, SA and Wright, B and Wilkins, MR and Timms, P and Belov, K}, title = {Adaptation and conservation insights from the koala genome.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1102-1111}, pmid = {29967444}, issn = {1546-1718}, support = {BB/J004669/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 GM092706/GM/NIGMS NIH HHS/United States ; }, abstract = {The koala, the only extant species of the marsupial family Phascolarctidae, is classified as 'vulnerable' due to habitat loss and widespread disease. We sequenced the koala genome, producing a complete and contiguous marsupial reference genome, including centromeres. We reveal that the koala's ability to detoxify eucalypt foliage may be due to expansions within a cytochrome P450 gene family, and its ability to smell, taste and moderate ingestion of plant secondary metabolites may be due to expansions in the vomeronasal and taste receptors. We characterized novel lactation proteins that protect young in the pouch and annotated immune genes important for response to chlamydial disease. Historical demography showed a substantial population crash coincident with the decline of Australian megafauna, while contemporary populations had biogeographic boundaries and increased inbreeding in populations affected by historic translocations. We identified genetically diverse populations that require habitat corridors and instituting of translocation programs to aid the koala's survival in the wild.}, } @article {pmid29967420, year = {2018}, author = {Orsi, WD}, title = {Ecology and evolution of seafloor and subseafloor microbial communities.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {11}, pages = {671-683}, doi = {10.1038/s41579-018-0046-8}, pmid = {29967420}, issn = {1740-1534}, abstract = {Vast regions of the dark ocean have ultra-slow rates of organic matter sedimentation, and their sediments are oxygenated to great depths yet have low levels of organic matter and cells. Primary production in the oxic seabed is supported by ammonia-oxidizing archaea, whereas in anoxic sediments, novel, uncultivated groups have the potential to produce H2 and CH4, which fuel anaerobic carbon fixation. Subseafloor bacteria have very low mutation rates, and their evolution is likely dominated by selection of different pre-adapted subseafloor taxa under oxic and anoxic conditions. In addition, the abundance and activity of viruses indicate that they affect the size, structure and selection of subseafloor communities. This Review highlights how microbial communities survive in the unique, nutrient-poor and energy-starved environment of the seabed, where they have the potential to influence global biochemical cycles.}, } @article {pmid29967384, year = {2018}, author = {Robinson, A}, title = {UNESCO's troubled drive for peace through science and culture.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {29-30}, doi = {10.1038/d41586-018-05602-2}, pmid = {29967384}, issn = {1476-4687}, } @article {pmid29967383, year = {2018}, author = {Sigel, E}, title = {Key receptor involved in neuronal signalling visualized.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {37-38}, doi = {10.1038/d41586-018-05538-7}, pmid = {29967383}, issn = {1476-4687}, mesh = {Humans ; *Neurons ; *Signal Transduction ; gamma-Aminobutyric Acid ; }, } @article {pmid29967382, year = {2018}, author = {Simmons, CA}, title = {Taking bioengineered heart valves from faulty to functional.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {42-43}, doi = {10.1038/d41586-018-05566-3}, pmid = {29967382}, issn = {1476-4687}, } @article {pmid29967308, year = {2018}, author = {Penn, A and Turner, JS}, title = {Can we identify general architectural principles that impact the collective behaviour of both human and animal systems?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967308}, issn = {1471-2970}, abstract = {The search for general common principles that unify disciplines is a longstanding challenge for interdisciplinary research. Architecture has always been an interdisciplinary pursuit, combining engineering, art and culture. The rise of biomimetic architecture adds to the interdisciplinary span. We discuss the similarities and differences among human and animal societies in how architecture influences their collective behaviour. We argue that the emergence of a fully biomimetic architecture involves breaking down what we call 'pernicious dualities' that have permeated our discourse for decades, artificial divisions between species, between organism and environment, between genotype and phenotype, and in the case of architecture, the supposed duality between the built environment and its builders. We suggest that niche construction theory may serve as a starting point for unifying our thinking across disciplines, taxa and spatial scales.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967307, year = {2018}, author = {Smith, JE and Gamboa, DA and Spencer, JM and Travenick, SJ and Ortiz, CA and Hunter, RD and Sih, A}, title = {Split between two worlds: automated sensing reveals links between above- and belowground social networks in a free-living mammal.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967307}, issn = {1471-2970}, abstract = {Many animals socialize in two or more major ecological contexts. In nature, these contexts often involve one situation in which space is more constrained (e.g. shared refuges, sleeping cliffs, nests, dens or burrows) and another situation in which animal movements are relatively free (e.g. in open spaces lacking architectural constraints). Although it is widely recognized that an individual's characteristics may shape its social life, the extent to which architecture constrains social decisions within and between habitats remains poorly understood. Here we developed a novel, automated-monitoring system to study the effects of personality, life-history stage and sex on the social network structure of a facultatively social mammal, the California ground squirrel (Otospermophilus beecheyi) in two distinct contexts: aboveground where space is relatively open and belowground where it is relatively constrained by burrow architecture. Aboveground networks reflected affiliative social interactions whereas belowground networks reflected burrow associations. Network structure in one context (belowground), along with preferential juvenile-adult associations, predicted structure in a second context (aboveground). Network positions of individuals were generally consistent across years (within contexts) and between ecological contexts (within years), suggesting that individual personalities and behavioural syndromes, respectively, contribute to the social network structure of these free-living mammals. Direct ties (strength) tended to be stronger in belowground networks whereas more indirect paths (betweenness centrality) flowed through individuals in aboveground networks. Belowground, females fostered significantly more indirect paths than did males. Our findings have important potential implications for disease and information transmission, offering new insights into the multiple factors contributing to social structures across ecological contexts.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967306, year = {2018}, author = {Pinter-Wollman, N and Jelić, A and Wells, NM}, title = {The impact of the built environment on health behaviours and disease transmission in social systems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967306}, issn = {1471-2970}, abstract = {The environment plays an important role in disease dynamics and in determining the health of individuals. Specifically, the built environment has a large impact on the prevention and containment of both chronic and infectious disease in humans and in non-human animals. The effects of the built environment on health can be direct, for example, by influencing environmental quality, or indirect by influencing behaviours that impact disease transmission and health. Furthermore, these impacts can happen at many scales, from the individual to the society, and from the design of the plates we eat from to the design of cities. In this paper, we review the ways that the built environment affects both the prevention and the containment of chronic and infectious disease. We bring examples from both human and animal societies and attempt to identify parallels and gaps between the study of humans and animals that can be capitalized on to advance the scope and perspective of research in each respective field. By consolidating this literature, we hope to highlight the importance of built structures in determining the complex dynamics of disease and in impacting the health behaviours of both humans and animals.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967305, year = {2018}, author = {Ireland, T and Garnier, S}, title = {Architecture, space and information in constructions built by humans and social insects: a conceptual review.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967305}, issn = {1471-2970}, abstract = {The similarities between the structures built by social insects and by humans have led to a convergence of interests between biologists and architects. This new, de facto interdisciplinary community of scholars needs a common terminology and theoretical framework in which to ground its work. In this conceptually oriented review paper, we review the terms 'information', 'space' and 'architecture' to provide definitions that span biology and architecture. A framework is proposed on which interdisciplinary exchange may be better served, with the view that this will aid better cross-fertilization between disciplines, working in the areas of collective behaviour and analysis of the structures and edifices constructed by non-humans; and to facilitate how this area of study may better contribute to the field of architecture. We then use these definitions to discuss the informational content of constructions built by organisms and the influence these have on behaviour, and vice versa. We review how spatial constraints inform and influence interaction between an organism and its environment, and examine the reciprocity of space and information on construction and the behaviour of humans and social insects.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967304, year = {2018}, author = {Alnabulsi, H and Drury, J and Templeton, A}, title = {Predicting collective behaviour at the Hajj: place, space and the process of cooperation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967304}, issn = {1471-2970}, abstract = {Around 2 million pilgrims attend the annual Hajj to Mecca and the holy places, which are subject to dense crowding. Both architecture and psychology can be part of disaster risk reduction in relation to crowding, since both can affect the nature of collective behaviour-particularly cooperation-among pilgrims. To date, collective behaviour at the Hajj has not been systematically investigated from a psychological perspective. We examined determinants of cooperation in the Grand Mosque and plaza during the pilgrimage. A questionnaire survey of 1194 pilgrims found that the Mosque was perceived by pilgrims as one of the most crowded ritual locations. Being in the plaza (compared with the Mosque) predicted the extent of cooperation, though crowd density did not. Shared social identity with the crowd explained more of the variance than both location and density. We examined some of the process underlying cooperation. The link between shared social identity and giving support to others was stronger in the plaza than in the Mosque, and suggests the role of place and space in modulating processes of cooperation in crowds. These findings have implications for disaster risk reduction and for applications such as computer simulations of crowds in pilgrimage locations.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967303, year = {2018}, author = {Bernstein, ES and Turban, S}, title = {The impact of the 'open' workspace on human collaboration.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967303}, issn = {1471-2970}, abstract = {Organizations' pursuit of increased workplace collaboration has led managers to transform traditional office spaces into 'open', transparency-enhancing architectures with fewer walls, doors and other spatial boundaries, yet there is scant direct empirical research on how human interaction patterns change as a result of these architectural changes. In two intervention-based field studies of corporate headquarters transitioning to more open office spaces, we empirically examined-using digital data from advanced wearable devices and from electronic communication servers-the effect of open office architectures on employees' face-to-face, email and instant messaging (IM) interaction patterns. Contrary to common belief, the volume of face-to-face interaction decreased significantly (approx. 70%) in both cases, with an associated increase in electronic interaction. In short, rather than prompting increasingly vibrant face-to-face collaboration, open architecture appeared to trigger a natural human response to socially withdraw from officemates and interact instead over email and IM. This is the first study to empirically measure both face-to-face and electronic interaction before and after the adoption of open office architecture. The results inform our understanding of the impact on human behaviour of workspaces that trend towards fewer spatial boundaries.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967302, year = {2018}, author = {Kabo, F}, title = {The architecture of network collective intelligence: correlations between social network structure, spatial layout and prestige outcomes in an office.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967302}, issn = {1471-2970}, abstract = {A social network represents interactions and knowledge that transcend the intelligence of any of its individual members. In this study, I examine the correlations between this network collective intelligence, spatial layout, and prestige or status outcomes at the individual and team levels in an organization. I propose that spatially influenced social cognition shapes which individuals become members of prestigious teams in organizations, and the prestige perception of teams by others in the organization. Prestige is a pathway to social rank, influence and upward mobility for individuals in organizations. For groups, perceived prestige of work teams is related to how team members identify with the group and with their collaborative behaviours. Prestige enhances a team's survivability and its access to resources. At the individual level, I ran two-stage Heckman sample selection models to examine the correlation between social network position and the number of prestigious projects a person is a member of, contingent on the association between physical space and social ties and networks. At the team level, I used linear regressions to examine the relationship among network structure, spatial proximity and the perceived prestige or innovativeness of a project team. In line with my hypotheses, for individuals there is a significant correlation between physical space and social networks, and contingent on that, between social network positions and the number of prestigious projects that a person is a member of. Also in accordance with my hypotheses, for teams there is a significant correlation between network structure and spatial proximity, and perceived prestige. While cross-sectional, the study findings illustrate the importance of considering the spatial domain in examinations of how network collective intelligence is related to organizational outcomes at the individual and team levels.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967301, year = {2018}, author = {Varoudis, T and Swenson, AG and Kirkton, SD and Waters, JS}, title = {Exploring nest structures of acorn dwelling ants with X-ray microtomography and surface-based three-dimensional visibility graph analysis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967301}, issn = {1471-2970}, abstract = {The physical spaces within which organisms live affect their biology and in many cases can be considered part of their extended phenotype. The nests of social insect societies have a fundamental impact on their ability to function as complex superorganisms. Ants in many species excavate elaborate subterranean nests, but others inhabit relatively small pre-formed cavities within rock crevices and hollow seeds. Temnothorax ants, which often nest within acorns, have become a model system for studying collective decision making. While these ants have demonstrated remarkable degrees of rationality and consistent precision with regard to their nest choices, never before has the fine scale internal architecture and spatial organization of their nests been investigated. We used X-ray microtomography to record high-resolution three-dimensional (3D) scans of Temnothorax colonies within their acorns. These data were then quantified using image segmentation and surface-based 3D visibility graph analysis, a new computational methodology for analysing spatial structures. The visibility graph analysis method integrates knowledge from the field of architecture with the empirical study of animal-built structures, thus providing the first methodological cross-disciplinary synergy of these two research areas. We found a surprisingly high surface area and degree of spatial heterogeneity within the acorn nests. Specific regions, such as those associated with the locations of queens and brood, were significantly more conducive to connectivity than others. From an architect's point of view, spatial analysis research has never focused on all-surface 3D movement, as we describe within ant nests. Therefore, we believe our approach will provide new methods for understanding both human design and the comparative biology of habitat spaces.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967300, year = {2018}, author = {Batty, M}, title = {Visualizing aggregate movement in cities.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, doi = {10.1098/rstb.2017.0236}, pmid = {29967300}, issn = {1471-2970}, abstract = {We argue here that despite the focus in cities on location and place, it is increasingly clear that a requisite understanding of how cities evolve and change depends on a thorough understanding of human movements at aggregate scales where we can observe emergent patterns in networks and flow systems. We argue that the location of activities must be understood as summations or syntheses of movements or flows, with a much clearer link between flows, activities and the networks that carry and support them. To this end, we introduce a generic class of models that enable aggregated flows of many different kinds of social and economic activity, ranging from the journey to work to email traffic, to be predicted using ideas from discrete choice theory in economics which has analogies to gravitation. We also argue that visualization is an essential construct in making sense of flows but that there are important limitations to illustrating pictorially systems with millions of component parts. To demonstrate these, we introduce a class of generic spatial interaction models and present two illustrations. Our first application is based on transit flows within the high-frequency city over very short time periods of minutes and hours for data from the London Underground. Our second application scales up these models from districts and cities to the nation, and we demonstrate how flows of people from home to work and vice versa define cities and related settlements at much coarser scales. We contrast this approach with more disaggregate, individual studies of flow systems in cities that we consider an essential complement to the ideas presented here.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967299, year = {2018}, author = {Kwapich, CL and Valentini, G and Hölldobler, B}, title = {The non-additive effects of body size on nest architecture in a polymorphic ant.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967299}, issn = {1471-2970}, abstract = {Like traditional organisms, eusocial insect societies express traits that are the target of natural selection. Variation at the colony level emerges from the combined attributes of thousands of workers and may yield characteristics not predicted from individual phenotypes. By manipulating the ratios of worker types, the basis of complex, colony-level traits can be reduced to the additive and non-additive interactions of their component parts. In this study, we investigated the independent and synergistic effects of body size on nest architecture in a seasonally polymorphic harvester ant, Veromessor pergandei Using network analysis, we compared wax casts of nests, and found that mixed-size groups built longer nests, excavated more sand and produced greater architectural complexity than single-sized worker groups. The nests built by polymorphic groups were not only larger in absolute terms, but larger than expected based on the combined contributions of both size classes in isolation. In effect, the interactions of different worker types yielded a colony-level trait that was not predicted from the sum of its parts. In nature, V. pergandei colonies with fewer fathers produce smaller workers each summer, and produce more workers annually. Because body size is linked to multiple colony-level traits, our findings demonstrate how selection acting on one characteristic, like mating frequency, could also shape unrelated characteristics, like nest architecture.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967298, year = {2018}, author = {Pinter-Wollman, N and Penn, A and Theraulaz, G and Fiore, SM}, title = {Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1753}, pages = {}, pmid = {29967298}, issn = {1471-2970}, abstract = {Built structures, such as animal nests or buildings that humans occupy, serve two overarching purposes: shelter and a space where individuals interact. The former has dominated much of the discussion in the literature. But, as the study of collective behaviour expands, it is time to elucidate the role of the built environment in shaping collective outcomes. Collective behaviour in social animals emerges from interactions, and collective cognition in humans emerges from communication and coordination. These collective actions have vast economic implications in human societies and critical fitness consequences in animal systems. Despite the obvious influence of space on interactions, because spatial proximity is necessary for an interaction to occur, spatial constraints are rarely considered in studies of collective behaviour or collective cognition. An interdisciplinary exchange between behavioural ecologists, evolutionary biologists, cognitive scientists, social scientists, architects and engineers can facilitate a productive exchange of ideas, methods and theory that could lead us to uncover unifying principles and novel research approaches and questions in studies of animal and human collective behaviour. This article, along with those in this theme issue aims to formalize and catalyse this interdisciplinary exchange.This article is part of the theme issue 'Interdisciplinary approaches for uncovering the impacts of architecture on collective behaviour'.}, } @article {pmid29967183, year = {2018}, author = {Hosoya, T and Sato-Kaneko, F and Ahmadi, A and Yao, S and Lao, F and Kitaura, K and Matsutani, T and Carson, DA and Hayashi, T}, title = {Induction of oligoclonal CD8 T cell responses against pulmonary metastatic cancer by a phospholipid-conjugated TLR7 agonist.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6836-E6844}, pmid = {29967183}, issn = {1091-6490}, support = {HHSN272200900034C/AI/NIAID NIH HHS/United States ; HHSN272201400051C/AI/NIAID NIH HHS/United States ; }, mesh = {Adenine/*analogs & derivatives/pharmacology ; Administration, Intranasal ; Animals ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Female ; Immunity, Cellular/*drug effects/immunology ; Killer Cells, Natural/immunology/pathology ; Lung Neoplasms/*drug therapy/immunology/pathology ; Membrane Glycoproteins/*agonists/immunology ; Mice ; Mice, Inbred BALB C ; Neoplasm Metastasis ; Phosphatidic Acids/*pharmacology ; Receptors, Antigen, T-Cell/immunology ; Toll-Like Receptor 7/*agonists/immunology ; }, abstract = {Recent advances in cancer immunotherapy have improved patient survival. However, only a minority of patients with pulmonary metastatic disease respond to treatment with checkpoint inhibitors. As an alternate approach, we have tested the ability of systemically administered 1V270, a toll-like receptor 7 (TLR7) agonist conjugated to a phospholipid, to inhibit lung metastases in two variant murine 4T1 breast cancer models, as well as in B16 melanoma, and Lewis lung carcinoma models. In the 4T1 breast cancer models, 1V270 therapy inhibited lung metastases if given up to a week after primary tumor initiation. The treatment protocol was facilitated by the minimal toxic effects exerted by the phospholipid TLR7 agonist compared with the unconjugated agonist. 1V270 exhibited a wide therapeutic window and minimal off-target receptor binding. The 1V270 therapy inhibited colonization by tumor cells in the lungs in an NK cell dependent manner. Additional experiments revealed that single administration of 1V270 led to tumor-specific CD8+ cell-dependent adaptive immune responses that suppressed late-stage metastatic tumor growth in the lungs. T cell receptor (TCR) repertoire analyses showed that 1V270 therapy induced oligoclonal T cells in the lungs and mediastinal lymph nodes. Different animals displayed commonly shared TCR clones following 1V270 therapy. Intranasal administration of 1V270 also suppressed lung metastasis and induced tumor-specific adaptive immune responses. These results indicate that systemic 1V270 therapy can induce tumor-specific cytotoxic T cell responses to pulmonary metastatic cancers and that TCR repertoire analyses can be used to monitor, and to predict, the response to therapy.}, } @article {pmid29967182, year = {2018}, author = {Hiratani, N and Fukai, T}, title = {Redundancy in synaptic connections enables neurons to learn optimally.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6871-E6879}, pmid = {29967182}, issn = {1091-6490}, mesh = {Animals ; Humans ; *Models, Neurological ; Neuronal Plasticity/*physiology ; Neurons/cytology/*physiology ; Synapses/*physiology ; }, abstract = {Recent experimental studies suggest that, in cortical microcircuits of the mammalian brain, the majority of neuron-to-neuron connections are realized by multiple synapses. However, it is not known whether such redundant synaptic connections provide any functional benefit. Here, we show that redundant synaptic connections enable near-optimal learning in cooperation with synaptic rewiring. By constructing a simple dendritic neuron model, we demonstrate that with multisynaptic connections synaptic plasticity approximates a sample-based Bayesian filtering algorithm known as particle filtering, and wiring plasticity implements its resampling process. Extending the proposed framework to a detailed single-neuron model of perceptual learning in the primary visual cortex, we show that the model accounts for many experimental observations. In particular, the proposed model reproduces the dendritic position dependence of spike-timing-dependent plasticity and the functional synaptic organization on the dendritic tree based on the stimulus selectivity of presynaptic neurons. Our study provides a conceptual framework for synaptic plasticity and rewiring.}, } @article {pmid29967181, year = {2018}, author = {Komatsu, M and Fagan, TJ and Krot, AN and Nagashima, K and Petaev, MI and Kimura, M and Yamaguchi, A}, title = {First evidence for silica condensation within the solar protoplanetary disk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7497-7502}, pmid = {29967181}, issn = {1091-6490}, abstract = {Calcium-aluminum-rich inclusions (CAIs) and amoeboid olivine aggregates (AOAs), a refractory component of chondritic meteorites, formed in a high-temperature region of the protoplanetary disk characterized by approximately solar chemical and oxygen isotopic (Δ17O ∼ -24‰) compositions, most likely near the protosun. Here we describe a 16O-rich (Δ17O ∼ -22 ± 2‰) AOA from the carbonaceous Renazzo-type (CR) chondrite Yamato-793261 containing both (i) an ultrarefractory CAI and (ii) forsterite, low-Ca pyroxene, and silica, indicating formation by gas-solid reactions over a wide temperature range from ∼1,800 to ∼1,150 K. This AOA provides direct evidence for gas-solid condensation of silica in a CAI/AOA-forming region. In a gas of solar composition, the Mg/Si ratio exceeds 1, and, therefore, silica is not predicted to condense under equilibrium conditions, suggesting that the AOA formed in a parcel of gas with fractionated Mg/Si ratio, most likely due to condensation of forsterite grains. Thermodynamic modeling suggests that silica formed by condensation of nebular gas depleted by ∼10× in H and He that cooled at 50 K/hour at total pressure of 10-4 bar. Condensation of silica from a hot, chemically fractionated gas could explain the origin of silica identified from infrared spectroscopy of remote protostellar disks.}, } @article {pmid29967180, year = {2018}, author = {Huang, HY and Rivas-Caicedo, A and Renevey, F and Cannelle, H and Peranzoni, E and Scarpellino, L and Hardie, DL and Pommier, A and Schaeuble, K and Favre, S and Vogt, TK and Arenzana-Seisdedos, F and Schneider, P and Buckley, CD and Donnadieu, E and Luther, SA}, title = {Identification of a new subset of lymph node stromal cells involved in regulating plasma cell homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6826-E6835}, pmid = {29967180}, issn = {1091-6490}, mesh = {Animals ; *Antibody Formation ; B-Cell Activating Factor/immunology ; Chemokine CXCL12/immunology ; Homeostasis/*immunology ; Interleukin-6/immunology ; Lymph Nodes/cytology/*immunology ; Male ; Mice ; Plasma Cells/cytology/*immunology ; Stromal Cells/cytology/immunology ; }, abstract = {Antibody-secreting plasma cells (PCs) arise rapidly during adaptive immunity to control infections. The early PCs are retained within the reactive lymphoid organ where their localization and homeostasis rely on extrinsic factors, presumably produced by local niche cells. While myeloid cells have been proposed to form those niches, the contribution by colocalizing stromal cells has remained unclear. Here, we characterized a subset of fibroblastic reticular cells (FRCs) that forms a dense meshwork throughout medullary cords of lymph nodes (LNs) where PCs reside. This medullary FRC type is shown to be anatomically, phenotypically, and functionally distinct from T zone FRCs, both in mice and humans. By using static and dynamic imaging approaches, we provide evidence that medullary FRCs are the main cell type in contact with PCs guiding them in their migration. Medullary FRCs also represent a major local source of the PC survival factors IL-6, BAFF, and CXCL12, besides also producing APRIL. In vitro, medullary FRCs alone or in combination with macrophages promote PC survival while other LN cell types do not have this property. Thus, we propose that this FRC subset, together with medullary macrophages, forms PC survival niches within the LN medulla, and thereby helps in promoting the rapid development of humoral immunity, which is critical in limiting early pathogen spread.}, } @article {pmid29967179, year = {2018}, author = {Varsano, N and Beghi, F and Elad, N and Pereiro, E and Dadosh, T and Pinkas, I and Perez-Berna, AJ and Jin, X and Kruth, HS and Leiserowitz, L and Addadi, L}, title = {Two polymorphic cholesterol monohydrate crystal structures form in macrophage culture models of atherosclerosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7662-7669}, pmid = {29967179}, issn = {1091-6490}, mesh = {Animals ; Atherosclerosis/*metabolism/pathology ; Cell Line ; Cholesterol/*metabolism ; Cryoelectron Microscopy ; Macrophages/*metabolism/ultrastructure ; Mice ; Plaque, Atherosclerotic/*metabolism/ultrastructure ; Tomography, X-Ray ; }, abstract = {The formation of atherosclerotic plaques in the blood vessel walls is the result of LDL particle uptake, and consequently of cholesterol accumulation in macrophage cells. Excess cholesterol accumulation eventually results in cholesterol crystal deposition, the hallmark of mature atheromas. We followed the formation of cholesterol crystals in J774A.1 macrophage cells with time, during accumulation of LDL particles, using a previously developed correlative cryosoft X-ray tomography (cryo-SXT) and stochastic optical reconstruction microscopy (STORM) technique. We show, in the initial accumulation stages, formation of small quadrilateral crystal plates associated with the cell plasma membrane, which may subsequently assemble into large aggregates. These plates match crystals of the commonly observed cholesterol monohydrate triclinic structure. Large rod-like cholesterol crystals form at a later stage in intracellular locations. Using cryotransmission electron microscopy (cryo-TEM) and cryoelectron diffraction (cryo-ED), we show that the structure of the large elongated rods corresponds to that of monoclinic cholesterol monohydrate, a recently determined polymorph of the triclinic crystal structure. These monoclinic crystals form with an unusual hollow cylinder or helical architecture, which is preserved in the mature rod-like crystals. The rod-like morphology is akin to that observed in crystals isolated from atheromas. We suggest that the crystals in the atherosclerotic plaques preserve in their morphology the memory of the structure in which they were formed. The identification of the polymorph structure, besides explaining the different crystal morphologies, may serve to elucidate mechanisms of cholesterol segregation and precipitation in atherosclerotic plaques.}, } @article {pmid29967178, year = {2018}, author = {Ravindran, S}, title = {QnAs with Lia Addadi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7644-7645}, pmid = {29967178}, issn = {1091-6490}, mesh = {Animals ; Atherosclerosis/genetics/*metabolism/pathology ; Gout/genetics/*metabolism/pathology ; Humans ; *Models, Biological ; Osteoporosis/genetics/*metabolism/pathology ; Portraits as Topic ; }, } @article {pmid29967177, year = {2018}, author = {Zhang, H and Liu, J and Qu, D and Wang, L and Wong, CM and Lau, CW and Huang, Y and Wang, YF and Huang, H and Xia, Y and Xiang, L and Cai, Z and Liu, P and Wei, Y and Yao, X and Ma, RCW and Huang, Y}, title = {Serum exosomes mediate delivery of arginase 1 as a novel mechanism for endothelial dysfunction in diabetes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6927-E6936}, pmid = {29967177}, issn = {1091-6490}, mesh = {Animals ; Aorta/*metabolism/pathology ; Arginase/*pharmacology ; *Diabetic Angiopathies/drug therapy/metabolism/pathology ; Endothelium, Vascular/*metabolism/pathology ; *Exosomes ; Mice ; }, abstract = {Exosomes, abundant in blood, deliver various molecules to recipient cells. Endothelial cells are directly exposed to circulating substances. However, how endothelial cells respond to serum exosomes (SExos) and the implications in diabetes-associated vasculopathy have never been explored. In the present study, we showed that SExos from diabetic db/db mice (db/db SExos) were taken up by aortic endothelial cells, which severely impaired endothelial function in nondiabetic db/m+ mice. The exosomal proteins, rather than RNAs, mostly account for db/db SExos-induced endothelial dysfunction. Comparative proteomics analysis showed significant increase of arginase 1 in db/db SExos. Silence or overexpression of arginase 1 confirmed its essential role in db/db SExos-induced endothelial dysfunction. This study is a demonstration that SExos deliver arginase 1 protein to endothelial cells, representing a cellular mechanism during development of diabetic endothelial dysfunction. The results expand the scope of blood-borne substances that monitor vascular homeostasis.}, } @article {pmid29967176, year = {2018}, author = {Bayer-Giraldi, M and Sazaki, G and Nagashima, K and Kipfstuhl, S and Vorontsov, DA and Furukawa, Y}, title = {Growth suppression of ice crystal basal face in the presence of a moderate ice-binding protein does not confer hyperactivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7479-7484}, pmid = {29967176}, issn = {1091-6490}, mesh = {Algal Proteins/*chemistry/metabolism ; Diatoms/*chemistry/metabolism ; *Freezing ; *Ice ; Microalgae/*chemistry/metabolism ; }, abstract = {Ice-binding proteins (IBPs) affect ice crystal growth by attaching to crystal faces. We present the effects on the growth of an ice single crystal caused by an ice-binding protein from the sea ice microalga Fragilariopsis cylindrus (fcIBP) that is characterized by the widespread domain of unknown function 3494 (DUF3494) and known to cause a moderate freezing point depression (below 1 °C). By the application of interferometry, bright-field microscopy, and fluorescence microscopy, we observed that the fcIBP attaches to the basal faces of ice crystals, thereby inhibiting their growth in the c direction and resulting in an increase in the effective supercooling with increasing fcIBP concentration. In addition, we observed that the fcIBP attaches to prism faces and inhibits their growth. In the event that the effective supercooling is small and crystals are faceted, this process causes an emergence of prism faces and suppresses crystal growth in the a direction. When the effective supercooling is large and ice crystals have developed into a dendritic shape, the suppression of prism face growth results in thinner dendrite branches, and growth in the a direction is accelerated due to enhanced latent heat dissipation. Our observations clearly indicate that the fcIBP occupies a separate position in the classification of IBPs due to the fact that it suppresses the growth of basal faces, despite its moderate freezing point depression.}, } @article {pmid29967175, year = {2018}, author = {Gorsich, EE and Etienne, RS and Medlock, J and Beechler, BR and Spaan, JM and Spaan, RS and Ezenwa, VO and Jolles, AE}, title = {Opposite outcomes of coinfection at individual and population scales.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7545-7550}, pmid = {29967175}, issn = {1091-6490}, mesh = {Animals ; *Brucellosis/epidemiology/microbiology/transmission/veterinary ; Buffaloes/*microbiology ; Cattle ; *Coinfection/epidemiology/microbiology/transmission/veterinary ; Female ; *Models, Biological ; *Tuberculosis, Bovine/epidemiology/microbiology/transmission ; }, abstract = {Coinfecting parasites and pathogens remain a leading challenge for global public health due to their consequences for individual-level infection risk and disease progression. However, a clear understanding of the population-level consequences of coinfection is lacking. Here, we constructed a model that includes three individual-level effects of coinfection: mortality, fecundity, and transmission. We used the model to investigate how these individual-level consequences of coinfection scale up to produce population-level infection patterns. To parameterize this model, we conducted a 4-y cohort study in African buffalo to estimate the individual-level effects of coinfection with two bacterial pathogens, bovine tuberculosis (bTB) and brucellosis, across a range of demographic and environmental contexts. At the individual level, our empirical results identified bTB as a risk factor for acquiring brucellosis, but we found no association between brucellosis and the risk of acquiring bTB. Both infections were associated with reductions in survival and neither infection was associated with reductions in fecundity. The model reproduced coinfection patterns in the data and predicted opposite impacts of coinfection at individual and population scales: Whereas bTB facilitated brucellosis infection at the individual level, our model predicted the presence of brucellosis to have a strong negative impact on bTB at the population level. In modeled populations where brucellosis was present, the endemic prevalence and basic reproduction number ([Formula: see text]) of bTB were lower than in populations without brucellosis. Therefore, these results provide a data-driven example of competition between coinfecting pathogens that occurs when one pathogen facilitates secondary infections at the individual level.}, } @article {pmid29967174, year = {2018}, author = {Nuebler, J and Fudenberg, G and Imakaev, M and Abdennur, N and Mirny, LA}, title = {Chromatin organization by an interplay of loop extrusion and compartmental segregation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6697-E6706}, pmid = {29967174}, issn = {1091-6490}, support = {R01 GM114190/GM/NIGMS NIH HHS/United States ; U54 DK107980/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle Proteins/metabolism ; Chromatin/*metabolism ; Chromatin Assembly and Disassembly/*physiology ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosomes, Mammalian/*metabolism ; *Models, Biological ; }, abstract = {Mammalian chromatin is spatially organized at many scales showing two prominent features in interphase: (i) alternating regions (1-10 Mb) of active and inactive chromatin that spatially segregate into different compartments, and (ii) domains (<1 Mb), that is, regions that preferentially interact internally [topologically associating domains (TADs)] and are central to gene regulation. There is growing evidence that TADs are formed by active extrusion of chromatin loops by cohesin, whereas compartmentalization is established according to local chromatin states. Here, we use polymer simulations to examine how loop extrusion and compartmental segregation work collectively and potentially interfere in shaping global chromosome organization. A model with differential attraction between euchromatin and heterochromatin leads to phase separation and reproduces compartmentalization as observed in Hi-C. Loop extrusion, essential for TAD formation, in turn, interferes with compartmentalization. Our integrated model faithfully reproduces Hi-C data from puzzling experimental observations where altering loop extrusion also led to changes in compartmentalization. Specifically, depletion of chromatin-associated cohesin reduced TADs and revealed finer compartments, while increased processivity of cohesin strengthened large TADs and reduced compartmentalization; and depletion of the TAD boundary protein CTCF weakened TADs while leaving compartments unaffected. We reveal that these experimental perturbations are special cases of a general polymer phenomenon of active mixing by loop extrusion. Our results suggest that chromatin organization on the megabase scale emerges from competition of nonequilibrium active loop extrusion and epigenetically defined compartment structure.}, } @article {pmid29967173, year = {2018}, author = {Lin, X and Xu, Y and Jiang, J and Lavine, M and Lavine, LC}, title = {Host quality induces phenotypic plasticity in a wing polyphenic insect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7563-7568}, pmid = {29967173}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; Female ; Hemiptera/anatomy & histology/*physiology ; Host-Parasite Interactions/*physiology ; Male ; Oryza/*parasitology ; Wings, Animal/anatomy & histology/*physiology ; }, abstract = {Food quality is a critical environmental condition that impacts an animal's growth and development. Many insects facing this challenge have evolved a phenotypically plastic, adaptive response. For example, many species of insect exhibit facultative wing growth, which reflects a physiological and evolutionary trade-off between dispersal and reproduction, triggered by environmental conditions. What the environmental cues are and how they are transduced to produce these alternative forms, and their associated ecological shift from dispersal to reproduction, remains an important unsolved problem in evolutionary ecology. In this study, we investigated the role that host quality has on the induction of wing development in a wing polyphenic insect exhibiting strong tradeoffs in investment between dispersal and reproduction, the brown planthopper, a serious rice pest in Asia. As rice plants grow, the short-winged brown planthopper dominates the population, but a shift occurs as the plants mature and senesce in the field such that long-winged brown planthoppers emerge and migrate. It remains unknown how changes in the rice plant induce development of the long-winged morph, despite recent discoveries on the role of the insulin and JNK signaling pathways in wing development. We found that by mimicking the glucose concentration of senescing rice plants, we significantly increased the proportion of long-winged female planthoppers. The effects of glucose on wing morph are additive with previously described effects of density. Our results show that host quality both directly regulates phenotypic plasticity and interacts with other factors such as density to produce the appropriate phenotype for specific environmental conditions.}, } @article {pmid29967172, year = {2018}, author = {Tabansky, I and Liang, Y and Frankfurt, M and Daniels, MA and Harrigan, M and Stern, S and Milner, TA and Leshan, R and Rama, R and Moll, T and Friedman, JM and Stern, JNH and Pfaff, DW}, title = {Molecular profiling of reticular gigantocellularis neurons indicates that eNOS modulates environmentally dependent levels of arousal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6900-E6909}, pmid = {29967172}, issn = {1091-6490}, support = {F32 HD081835/HD/NICHD NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Arousal/*physiology ; *Brain/blood supply/cytology/metabolism ; Cerebrovascular Circulation/*physiology ; Genetic Loci ; Mice ; Mice, Transgenic ; Neurons/cytology/*metabolism ; *Nitric Oxide Synthase Type III/biosynthesis/genetics ; Signal Transduction/*physiology ; }, abstract = {Neurons of the medullary reticular nucleus gigantocellularis (NGC) and their targets have recently been a focus of research on mechanisms supporting generalized CNS arousal (GA) required for proper cognitive functions. Using the retro-TRAP method, we characterized transcripts enriched in NGC neurons which have projections to the thalamus. The unique expression and activation of the endothelial nitric oxide (eNOS) signaling pathway in these cells and their intimate connections with blood vessels indicate that these neurons exert direct neurovascular coupling. Production of nitric oxide (NO) within eNOS-positive NGC neurons increases after environmental perturbations, indicating a role for eNOS/NO in modulating environmentally appropriate levels of GA. Inhibition of NO production causes dysregulated behavioral arousal after exposure to environmental perturbation. Further, our findings suggest interpretations for associations between psychiatric disorders and mutations in the eNOS locus.}, } @article {pmid29967171, year = {2018}, author = {Daniel, L and Cerutti, E and Donnio, LM and Nonnekens, J and Carrat, C and Zahova, S and Mari, PO and Giglia-Mari, G}, title = {Mechanistic insights in transcription-coupled nucleotide excision repair of ribosomal DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6770-E6779}, pmid = {29967171}, issn = {1091-6490}, mesh = {Cell Line, Transformed ; *DNA Repair ; DNA, Ribosomal/genetics/*metabolism ; Humans ; RNA Polymerase I/genetics/*metabolism ; *Transcription, Genetic ; Ultraviolet Rays ; }, abstract = {Nucleotide excision repair (NER) guarantees genome integrity against UV light-induced DNA damage. After UV irradiation, cells have to cope with a general transcriptional block. To ensure UV lesions repair specifically on transcribed genes, NER is coupled with transcription in an extremely organized pathway known as transcription-coupled repair. In highly metabolic cells, more than 60% of total cellular transcription results from RNA polymerase I activity. Repair of the mammalian transcribed ribosomal DNA has been scarcely studied. UV lesions severely block RNA polymerase I activity and the full transcription-coupled repair machinery corrects damage on actively transcribed ribosomal DNAs. After UV irradiation, RNA polymerase I is more bound to the ribosomal DNA and both are displaced to the nucleolar periphery. Importantly, the reentry of RNA polymerase I and the ribosomal DNA is dependent on the presence of UV lesions on DNA and independent of transcription restart.}, } @article {pmid29967170, year = {2018}, author = {Jones, LK and Jennings, BM and Higgins, MK and de Waal, FBM}, title = {Ethological observations of social behavior in the operating room.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7575-7580}, pmid = {29967170}, issn = {1091-6490}, support = {R03 HS023403/HS/AHRQ HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {*Conflict (Psychology) ; Female ; Humans ; *Interpersonal Relations ; Male ; *Operating Rooms ; *Social Behavior ; *Surgical Procedures, Operative ; }, abstract = {Operating rooms (ORs) are inhabited by hierarchical, mixed-gender clinical teams that are often prone to conflict. In evolutionary terms, one expects more within- than between-gender rivalries, especially since the OR is a place where all sorts of social interactions occur, not merely technical communications. To document the full range of behavior, the present study used ethological observation techniques, recording live all social behavior by the team. Using an ethogram, 6,348 spontaneous social interactions and nontechnical communications were timestamped during 200 surgical procedures. Cooperation sequences (59.0%) were more frequent than conflict sequences (2.8%), which ranged from constructive differences of opinion to discord and distraction that could jeopardize patient safety. Behavior varied by clinical role and with the gender composition in the OR. Conflict was initiated mostly down the hierarchy between individuals several ranks apart. Cooperation tended to increase with a rising proportion of females in the OR, but the most pronounced effect concerned the interaction between both genders. If the attending surgeon's gender differed from that of the majority of other personnel in the OR, cooperation was significantly more common.}, } @article {pmid29967169, year = {2018}, author = {Smith, GP and Fraccia, TP and Todisco, M and Zanchetta, G and Zhu, C and Hayden, E and Bellini, T and Clark, NA}, title = {Backbone-free duplex-stacked monomer nucleic acids exhibiting Watson-Crick selectivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {33}, pages = {E7658-E7664}, pmid = {29967169}, issn = {1091-6490}, mesh = {Hydrogen Bonding ; Liquid Crystals ; *Nucleic Acid Conformation ; X-Ray Diffraction ; }, abstract = {We demonstrate that nucleic acid (NA) mononucleotide triphosphates (dNTPs and rNTPs), at sufficiently high concentration and low temperature in aqueous solution, can exhibit a phase transition in which chromonic columnar liquid crystal ordering spontaneously appears. Remarkably, this polymer-free state exhibits, in a self-assembly of NA monomers, the key structural elements of biological nucleic acids, including: long-ranged duplex stacking of base pairs, complementarity-dependent partitioning of molecules, and Watson-Crick selectivity, such that, among all solutions of adenosine, cytosine, guanine, and thymine NTPs and their binary mixtures, duplex columnar ordering is most stable in the A-T and C-G combinations.}, } @article {pmid29967168, year = {2018}, author = {}, title = {Correction for Edwards et al., Insight from the maximal activation of the signal transduction excitable network in Dictyostelium discoideum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6671}, doi = {10.1073/pnas.1809928115}, pmid = {29967168}, issn = {1091-6490}, support = {R35 GM118177/GM/NIGMS NIH HHS/United States ; }, } @article {pmid29967167, year = {2018}, author = {Long, JZ and Roche, AM and Berdan, CA and Louie, SM and Roberts, AJ and Svensson, KJ and Dou, FY and Bateman, LA and Mina, AI and Deng, Z and Jedrychowski, MP and Lin, H and Kamenecka, TM and Asara, JM and Griffin, PR and Banks, AS and Nomura, DK and Spiegelman, BM}, title = {Ablation of PM20D1 reveals N-acyl amino acid control of metabolism and nociception.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6937-E6945}, pmid = {29967167}, issn = {1091-6490}, support = {R00 DK105203/DK/NIDDK NIH HHS/United States ; R00 DK111916/DK/NIDDK NIH HHS/United States ; R01 DK061562/DK/NIDDK NIH HHS/United States ; R01 CA172667/CA/NCI NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; K99 DK111916/DK/NIDDK NIH HHS/United States ; R37 DK031405/DK/NIDDK NIH HHS/United States ; R01 DK031405/DK/NIDDK NIH HHS/United States ; K99 DK105203/DK/NIDDK NIH HHS/United States ; }, mesh = {Amidohydrolases/genetics/*metabolism ; Animals ; Body Temperature/physiology ; Glutamine/genetics/*metabolism/pharmacology ; Mice ; Mice, Knockout ; Nociception/drug effects/*physiology ; Oleic Acids/genetics/*metabolism/pharmacology ; Signal Transduction/*physiology ; TRPV Cation Channels/genetics/metabolism ; }, abstract = {N-acyl amino acids (NAAs) are a structurally diverse class of bioactive signaling lipids whose endogenous functions have largely remained uncharacterized. To clarify the physiologic roles of NAAs, we generated mice deficient in the circulating enzyme peptidase M20 domain-containing 1 (PM20D1). Global PM20D1-KO mice have dramatically reduced NAA hydrolase/synthase activities in tissues and blood with concomitant bidirectional dysregulation of endogenous NAAs. Compared with control animals, PM20D1-KO mice exhibit a variety of metabolic and pain phenotypes, including insulin resistance, altered body temperature in cold, and antinociceptive behaviors. Guided by these phenotypes, we identify N-oleoyl-glutamine (C18:1-Gln) as a key PM20D1-regulated NAA. In addition to its mitochondrial uncoupling bioactivity, C18:1-Gln also antagonizes certain members of the transient receptor potential (TRP) calcium channels including TRPV1. Direct administration of C18:1-Gln to mice is sufficient to recapitulate a subset of phenotypes observed in PM20D1-KO animals. These data demonstrate that PM20D1 is a dominant enzymatic regulator of NAA levels in vivo and elucidate physiologic functions for NAA signaling in metabolism and nociception.}, } @article {pmid29967166, year = {2018}, author = {Cheng, H and Xuan, H and Green, CD and Han, Y and Sun, N and Shen, H and McDermott, J and Bennett, DA and Lan, F and Han, JJ}, title = {Repression of human and mouse brain inflammaging transcriptome by broad gene-body histone hyperacetylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7611-7616}, pmid = {29967166}, issn = {1091-6490}, support = {P30 AG010161/AG/NIA NIH HHS/United States ; R01 AG015819/AG/NIA NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; RF1 AG015819/AG/NIA NIH HHS/United States ; }, mesh = {Acetylation ; Aging/genetics/*metabolism ; Animals ; Brain/*metabolism ; Gene Expression Profiling ; Histones/genetics/*metabolism ; Humans ; Inflammation/genetics/metabolism ; Mice ; *Promoter Regions, Genetic ; *Transcription, Genetic ; *Transcriptome ; }, abstract = {Brain "inflammaging," a low-grade and chronic inflammation, is a major hallmark for aging-related neurodegenerative diseases. Here, by profiling H3K27ac and gene expression patterns in human and mouse brains, we found that age-related up-regulated (Age-Up) and down-regulated (Age-Down) genes have distinct H3K27ac patterns. Although both groups show promoter H3K27ac, the Age-Up genes, enriched for inflammation-related functions, are additionally marked by broad H3K27ac distribution over their gene bodies, which is progressively reduced during aging. Age-related gene expression changes can be predicted by gene-body H3K27ac level. Contrary to the presumed transcription activation function of promoter H3K27ac, we found that broad gene-body hyper H3K27ac suppresses overexpression of inflammaging genes. Altogether, our findings revealed opposite regulations by H3K27ac of Age-Up and Age-Down genes and a mode of broad gene-body H3K27ac in repressing transcription.}, } @article {pmid29967165, year = {2018}, author = {Kirkman, LA and Zhan, W and Visone, J and Dziedziech, A and Singh, PK and Fan, H and Tong, X and Bruzual, I and Hara, R and Kawasaki, M and Imaeda, T and Okamoto, R and Sato, K and Michino, M and Alvaro, EF and Guiang, LF and Sanz, L and Mota, DJ and Govindasamy, K and Wang, R and Ling, Y and Tumwebaze, PK and Sukenick, G and Shi, L and Vendome, J and Bhanot, P and Rosenthal, PJ and Aso, K and Foley, MA and Cooper, RA and Kafsack, B and Doggett, JS and Nathan, CF and Lin, G}, title = {Antimalarial proteasome inhibitor reveals collateral sensitivity from intersubunit interactions and fitness cost of resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6863-E6870}, pmid = {29967165}, issn = {1091-6490}, support = {R21 AI094167/AI/NIAID NIH HHS/United States ; R21 AI101393/AI/NIAID NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R21 AI123794/AI/NIAID NIH HHS/United States ; R01 AI075045/AI/NIAID NIH HHS/United States ; R56 AI075045/AI/NIAID NIH HHS/United States ; IK2 BX002440/BX/BLRD VA/United States ; }, mesh = {Antimalarials/*chemistry ; Artemisinins/chemistry ; Bortezomib/chemistry ; Drug Resistance, Microbial ; Humans ; Lactones/chemistry ; Oligopeptides/chemistry ; Plasmodium falciparum/*enzymology ; Proteasome Endopeptidase Complex/*chemistry ; Proteasome Inhibitors/*chemistry ; Protozoan Proteins/*antagonists & inhibitors/chemistry ; }, abstract = {We describe noncovalent, reversible asparagine ethylenediamine (AsnEDA) inhibitors of the Plasmodium falciparum proteasome (Pf20S) β5 subunit that spare all active subunits of human constitutive and immuno-proteasomes. The compounds are active against erythrocytic, sexual, and liver-stage parasites, against parasites resistant to current antimalarials, and against P. falciparum strains from patients in Africa. The β5 inhibitors synergize with a β2 inhibitor in vitro and in mice and with artemisinin. P. falciparum selected for resistance to an AsnEDA β5 inhibitor surprisingly harbored a point mutation in the noncatalytic β6 subunit. The β6 mutant was resistant to the species-selective Pf20S β5 inhibitor but remained sensitive to the species-nonselective β5 inhibitors bortezomib and carfilzomib. Moreover, resistance to the Pf20S β5 inhibitor was accompanied by increased sensitivity to a Pf20S β2 inhibitor. Finally, the β5 inhibitor-resistant mutant had a fitness cost that was exacerbated by irradiation. Thus, used in combination, multistage-active inhibitors of the Pf20S β5 and β2 subunits afford synergistic antimalarial activity with a potential to delay the emergence of resistance to artemisinins and each other.}, } @article {pmid29967164, year = {2018}, author = {Pichoff, S and Du, S and Lutkenhaus, J}, title = {Disruption of divisome assembly rescued by FtsN-FtsA interaction in Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6855-E6862}, pmid = {29967164}, issn = {1091-6490}, mesh = {ATP-Binding Cassette Transporters/genetics/metabolism ; Cell Cycle Proteins/genetics/metabolism ; Cell Division/*physiology ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics/metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Periplasm/genetics/*metabolism ; }, abstract = {Cell division requires the assembly of a protein complex called the divisome. The divisome assembles in a hierarchical manner, with FtsA functioning as a hub to connect the Z-ring with the rest of the divisome and FtsN arriving last to activate the machine to synthesize peptidoglycan. FtsEX arrives as the Z-ring forms and acts on FtsA to initiate recruitment of the other divisome components. In the absence of FtsEX, recruitment is blocked; however, a multitude of conditions allow FtsEX to be bypassed. Here, we find that all such FtsEX bypass conditions, as well as the bypass of FtsK, depend upon the interaction of FtsN with FtsA, which promotes the back-recruitment of the late components of the divisome. Furthermore, our results suggest that these bypass conditions enhance the weak interaction of FtsN with FtsA and its periplasmic partners so that the divisome proteins are brought to the Z-ring when the normal hierarchical pathway is disrupted.}, } @article {pmid29967163, year = {2018}, author = {Gonzalez, D and Sabnis, A and Foster, KR and Mavridou, DAI}, title = {Costs and benefits of provocation in bacterial warfare.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7593-7598}, pmid = {29967163}, issn = {1091-6490}, support = {MR/M009505/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Warfare ; *Biological Warfare Agents ; *Escherichia coli ; Humans ; *Models, Biological ; }, abstract = {Competition in animals involves a wide variety of aggressive behaviors. One of the most sophisticated strategies for a focal actor is to provoke a competitor into uncontrolled aggression toward other competitors. Like animals, bacteria rely on a broad spectrum of molecular weapons, some of which provoke potential rivals by triggering retaliation. While bacterial provocation is well documented, its potential adaptive value has received little attention. Here, we examine the costs and benefits of provocation using mathematical modeling and experiments with Escherichia coli strains encoding colicin toxins. We show that provocation is typically costly in one-to-one encounters because a provoking strain receives a strong reciprocal attack compared with nonprovoking strains. By contrast, provocation can be strongly beneficial in communities including more than two toxin-producing strains, especially when the provoker is shielded from, or resistant to, its opponents' toxins. In these scenarios, we demonstrate that the benefit of provocation derives from a "divide-and-conquer" effect by which aggression-provoking toxin producers force their competitors into increased reciprocal aggression, leading to their cross-elimination. Furthermore, we show that this effect can be mimicked by using antibiotics that promote warfare among strains in a bacterial community, highlighting the potential of provocation as an antimicrobial approach.}, } @article {pmid29967162, year = {2018}, author = {Liao, L and Schaefer, AL and Coutinho, BG and Brown, PJB and Greenberg, EP}, title = {An aryl-homoserine lactone quorum-sensing signal produced by a dimorphic prosthecate bacterium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7587-7592}, pmid = {29967162}, issn = {1091-6490}, support = {R01 GM059026/GM/NIGMS NIH HHS/United States ; }, mesh = {4-Butyrolactone/*analogs & derivatives/biosynthesis/genetics ; Alphaproteobacteria/*physiology ; *Bacterial Proteins/genetics/metabolism ; Biofilms/*growth & development ; *Carrier Proteins/genetics/metabolism ; Quorum Sensing/*physiology ; Signal Transduction/*physiology ; }, abstract = {Many species of Proteobacteria produce acyl-homoserine lactone (AHL) compounds as quorum-sensing (QS) signals for cell density-dependent gene regulation. Most known AHL synthases, LuxI-type enzymes, produce fatty AHLs, and the fatty acid moiety is derived from an acyl-acyl carrier protein (ACP) intermediate in fatty acid biosynthesis. Recently, a class of LuxI homologs has been shown to use CoA-linked aromatic or amino acid substrates for AHL synthesis. By using an informatics approach, we found the CoA class of LuxI homologs exists primarily in α-Proteobacteria. The genome of Prosthecomicrobium hirschii, a dimorphic prosthecate bacterium, possesses a luxI-like AHL synthase gene that we predicted to encode a CoA-utilizing enzyme. We show the P. hirschii LuxI homolog catalyzes synthesis of phenylacetyl-homoserine lactone (PA-HSL). Our experiments show P. hirschii obtains phenylacetate from its environment and uses a CoA ligase to produce the phenylacetyl-CoA substrate for the LuxI homolog. By using an AHL degrading enzyme, we showed that PA-HSL controls aggregation, biofilm formation, and pigment production in P. hirschii These findings advance a limited understanding of the CoA-dependent AHL synthases. We describe how to identify putative members of the class, we describe a signal synthesized by using an environmental aromatic acid, and we identify phenotypes controlled by the aryl-HSL.}, } @article {pmid29967161, year = {2018}, author = {}, title = {Correction for LeClere et al., Cross-resistance to dicamba, 2,4-D, and fluroxypyr in Kochia scoparia is endowed by a mutation in an AUX/IAA gene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6668}, doi = {10.1073/pnas.1809836115}, pmid = {29967161}, issn = {1091-6490}, } @article {pmid29967160, year = {2018}, author = {Swanson, LW and Hahn, JD and Jeub, LGS and Fortunato, S and Sporns, O}, title = {Subsystem organization of axonal connections within and between the right and left cerebral cortex and cerebral nuclei (endbrain).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6910-E6919}, pmid = {29967160}, issn = {1091-6490}, mesh = {Animals ; Axons/*metabolism ; *Cerebral Cortex/cytology/metabolism ; *Connectome ; *Models, Neurological ; *Prosencephalon/cytology/metabolism ; Rats ; }, abstract = {The endbrain (telencephalon) is at the rostral end of the central nervous system and is primarily responsible for supporting cognition and affect. Structurally, it consists of right and left cerebral hemispheres, each parceled into multiple cortical and nuclear gray matter regions. The global network organization of axonal macroconnections between the 244 regions forming the endbrain was analyzed with a multiresolution consensus clustering (MRCC) method that provides a hierarchical description of community clustering (modules or subsystems) within the network. Experimental evidence was collated from the neuroanatomical literature for the existence of 10,002 of a possible 59,292 connections within the network, and they cluster into four top-level subsystems and 60 bottom-level subsystems arranged in a 50-level hierarchy. Two top-level subsystems are bihemispheric: One deals with auditory and visual information, and the other corresponds broadly to the default mode network. The other two top-level subsystems are bilaterally symmetrical, and each deals broadly with somatic and visceral information. Because the entire endbrain connection matrix was assembled from multiple subconnectomes, it was easy to show that the status of a region as a connectivity hub is not absolute but, instead, depends on the size and coverage of its anatomical neighborhood. It was also shown numerically that creating an ultradense connection matrix by converting all "absent" connections to a "very weak" connection weight has virtually no effect on the clustering hierarchy. The next logical step in this project is to complete the forebrain connectome by adding the thalamus and hypothalamus (together, the interbrain) to the endbrain analysis.}, } @article {pmid29967159, year = {2018}, author = {Chung, JY and Vaziri, A and Mahadevan, L}, title = {Reprogrammable Braille on an elastic shell.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7509-7514}, pmid = {29967159}, issn = {1091-6490}, abstract = {We describe a minimal realization of reversibly programmable matter in the form of a featureless smooth elastic plate that has the capacity to store information in a Braille-like format as a sequence of stable discrete dimples. Simple experiments with cylindrical and spherical shells show that we can control the number, location, and the temporal order of these dimples, which can be written and erased at will. Theoretical analysis of the governing equations in a specialized setting and numerical simulations of the complete equations allow us to characterize the phase diagram for the formation of these localized elastic states, elastic bits (e-bits), consistent with our observations. Given that the inherent bistability and hysteresis in these low-dimensional systems arise exclusively due to the geometrical-scale separation, independent of material properties or absolute scale, our results might serve as alternate approaches to small-scale mechanical memories.}, } @article {pmid29967158, year = {2018}, author = {Balsevich, G and Sticht, M and Bowles, NP and Singh, A and Lee, TTY and Li, Z and Chelikani, PK and Lee, FS and Borgland, SL and Hillard, CJ and McEwen, BS and Hill, MN}, title = {Role for fatty acid amide hydrolase (FAAH) in the leptin-mediated effects on feeding and energy balance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7605-7610}, pmid = {29967158}, issn = {1091-6490}, support = {R01 MH041256/MH/NIMH NIH HHS/United States ; R37 MH041256/MH/NIMH NIH HHS/United States ; FDN-143329//CIHR/Canada ; FDN-147473//CIHR/Canada ; }, mesh = {Amidohydrolases/genetics/*metabolism ; Animals ; Arachidonic Acids/*metabolism ; Body Weight/drug effects/genetics ; Dietary Fats/pharmacology ; *Eating/drug effects/genetics ; Endocannabinoids/*metabolism ; Energy Metabolism/*drug effects ; Gene Knock-In Techniques ; Hypothalamus/*metabolism ; Leptin/deficiency/*pharmacology ; Male ; Mice ; Mice, Knockout ; Polymorphism, Genetic ; Polyunsaturated Alkamides/*metabolism ; }, abstract = {Endocannabinoid signaling regulates feeding and metabolic processes and has been linked to obesity development. Several hormonal signals, such as glucocorticoids and ghrelin, regulate feeding and metabolism by engaging the endocannabinoid system. Similarly, studies have suggested that leptin interacts with the endocannabinoid system, yet the mechanism and functional relevance of this interaction remain elusive. Therefore, we explored the interaction between leptin and endocannabinoid signaling with a focus on fatty acid amide hydrolase (FAAH), the primary degradative enzyme for the endocannabinoid N-arachidonoylethanolamine (anandamide; AEA). Mice deficient in leptin exhibited elevated hypothalamic AEA levels and reductions in FAAH activity while leptin administration to WT mice reduced AEA content and increased FAAH activity. Following high fat diet exposure, mice developed resistance to the effects of leptin administration on hypothalamic AEA content and FAAH activity. At a functional level, pharmacological inhibition of FAAH was sufficient to prevent leptin-mediated effects on body weight and food intake. Using a novel knock-in mouse model recapitulating a common human polymorphism (FAAH C385A; rs324420), which reduces FAAH activity, we investigated whether human genetic variance in FAAH affects leptin sensitivity. While WT (CC) mice were sensitive to leptin-induced reductions in food intake and body weight gain, low-expressing FAAH (AA) mice were unresponsive. These data demonstrate that FAAH activity is required for leptin's hypophagic effects and, at a translational level, suggest that a genetic variant in the FAAH gene contributes to differences in leptin sensitivity in human populations.}, } @article {pmid29967157, year = {2018}, author = {Taylor, WTT and Bayarsaikhan, J and Tuvshinjargal, T and Bender, S and Tromp, M and Clark, J and Lowry, KB and Houle, JL and Staszewski, D and Whitworth, J and Fitzhugh, W and Boivin, N}, title = {Origins of equine dentistry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6707-E6715}, pmid = {29967157}, issn = {1091-6490}, mesh = {Animals ; Dentistry/*veterinary ; *Domestication ; *History of Dentistry ; History, Ancient ; *Horses ; Humans ; }, abstract = {From the American West to the steppes of Eurasia, the domestic horse transformed human societies, providing rapid transport, communication, and military power, and serving as an important subsistence animal. Because of the importance of oral equipment for horse riding, dentistry is an essential component of modern horse care. In the open grasslands of northeast Asia, horses remain the primary form of transport for many herders. Although free-range grazing on gritty forage mitigates many equine dental issues, contemporary Mongolian horsemen nonetheless practice some forms of dentistry, including the removal of problematic deciduous teeth and the vestigial first premolar ("wolf tooth"). Here, we present archaezoological data from equine skeletal remains spanning the past 3,200 y, indicating that nomadic dental practices have great antiquity. Anthropogenic modifications to malerupted deciduous central incisors in young horses from the Late Bronze Age demonstrate their attempted removal, coinciding with the local innovation or adoption of horseback riding and the florescence of Mongolian pastoral society. Horse specimens from this period show no evidence of first premolar removal, which we first identify in specimens dating to ca. 750 BCE. The onset of premolar extraction parallels the archaeological appearance of jointed bronze and iron bits, suggesting that this technological shift prompted innovations in dentistry that improved horse health and horse control. These discoveries provide the earliest directly dated evidence for veterinary dentistry, and suggest that innovations in equine care by nomadic peoples ca. 1150 BCE enabled the use of horses for increasingly sophisticated mounted riding and warfare.}, } @article {pmid29967156, year = {2018}, author = {Mühlemann, B and Margaryan, A and Damgaard, PB and Allentoft, ME and Vinner, L and Hansen, AJ and Weber, A and Bazaliiskii, VI and Molak, M and Arneborg, J and Bogdanowicz, W and Falys, C and Sablin, M and Smrčka, V and Sten, S and Tashbaeva, K and Lynnerup, N and Sikora, M and Smith, DJ and Fouchier, RAM and Drosten, C and Sjögren, KG and Kristiansen, K and Willerslev, E and Jones, TC}, title = {Ancient human parvovirus B19 in Eurasia reveals its long-term association with humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7557-7562}, pmid = {29967156}, issn = {1091-6490}, mesh = {Erythema Infectiosum/*genetics/history ; *Evolution, Molecular ; *Genome, Viral ; *Genotype ; History, 19th Century ; History, 20th Century ; Humans ; Parvovirus B19, Human/*genetics ; *Phylogeny ; *Sequence Analysis, DNA ; }, abstract = {Human parvovirus B19 (B19V) is a ubiquitous human pathogen associated with a number of conditions, such as fifth disease in children and arthritis and arthralgias in adults. B19V is thought to evolve exceptionally rapidly among DNA viruses, with substitution rates previously estimated to be closer to those typical of RNA viruses. On the basis of genetic sequences up to ∼70 years of age, the most recent common ancestor of all B19V has been dated to the early 1800s, and it has been suggested that genotype 1, the most common B19V genotype, only started circulating in the 1960s. Here we present 10 genomes (63.9-99.7% genome coverage) of B19V from dental and skeletal remains of individuals who lived in Eurasia and Greenland from ∼0.5 to ∼6.9 thousand years ago (kya). In a phylogenetic analysis, five of the ancient B19V sequences fall within or basal to the modern genotype 1, and five fall basal to genotype 2, showing a long-term association of B19V with humans. The most recent common ancestor of all B19V is placed ∼12.6 kya, and we find a substitution rate that is an order of magnitude lower than inferred previously. Further, we are able to date the recombination event between genotypes 1 and 3 that formed genotype 2 to ∼5.0-6.8 kya. This study emphasizes the importance of ancient viral sequences for our understanding of virus evolution and phylogenetics.}, } @article {pmid29967155, year = {2018}, author = {Marshall, AN and Han, J and Kim, M and van Hoof, A}, title = {Conservation of mRNA quality control factor Ski7 and its diversification through changes in alternative splicing and gene duplication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6808-E6816}, pmid = {29967155}, issn = {1091-6490}, support = {R01 GM099790/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adaptor Proteins, Signal Transducing/genetics/metabolism ; *Alternative Splicing ; *Evolution, Molecular ; *Gene Duplication ; *Saccharomyces cerevisiae/genetics/metabolism ; *Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {Eukaryotes maintain fidelity of gene expression by preferential degradation of aberrant mRNAs that arise by errors in RNA processing reactions. In Saccharomyces cerevisiae, Ski7 plays an important role in this mRNA quality control by mediating mRNA degradation by the RNA exosome. Ski7 was initially thought to be restricted to Saccharomyces cerevisiae and close relatives because the SKI7 gene and its paralog HBS1 arose by whole genome duplication (WGD) in a recent ancestor. We have recently shown that the preduplication gene was alternatively spliced and that Ski7 function predates WGD. Here, we use transcriptome analysis of diverse eukaryotes to show that diverse eukaryotes use alternative splicing of SKI7/HBS1 to encode two proteins. Although alternative splicing affects the same intrinsically disordered region of the protein, the pattern of splice site usage varies. This alternative splicing event arose in an early eukaryote that is a common ancestor of plants, animals, and fungi. Remarkably, through changes in alternative splicing and gene duplication, the Ski7 protein has diversified such that different species express one of four distinct Ski7-like proteins. We also show experimentally that the Saccharomyces cerevisiae SKI7 gene has undergone multiple changes that are incompatible with the Hbs1 function and may also have undergone additional changes to optimize mRNA quality control. The combination of transcriptome analysis in diverse eukaryotes and genetic analysis in yeast clarifies the mechanism by which a Ski7-like protein is expressed across eukaryotes and provides a unique view of changes in alternative splicing patterns of one gene over long evolutionary time.}, } @article {pmid29967154, year = {2018}, author = {Sargent, M and Barrera, Y and Nehrkorn, T and Hutyra, LR and Gately, CK and Jones, T and McKain, K and Sweeney, C and Hegarty, J and Hardiman, B and Wang, JA and Wofsy, SC}, title = {Anthropogenic and biogenic CO2 fluxes in the Boston urban region.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7491-7496}, pmid = {29967154}, issn = {1091-6490}, mesh = {Atmosphere/*analysis ; Boston ; Carbon Dioxide/*analysis ; Greenhouse Gases/*analysis ; *Models, Theoretical ; *Urban Renewal ; }, abstract = {With the pending withdrawal of the United States from the Paris Climate Accord, cities are now leading US actions toward reducing greenhouse gas emissions. Implementing effective mitigation strategies requires the ability to measure and track emissions over time and at various scales. We report CO2 emissions in the Boston, MA, urban region from September 2013 to December 2014 based on atmospheric observations in an inverse model framework. Continuous atmospheric measurements of CO2 from five sites in and around Boston were combined with a high-resolution bottom-up CO2 emission inventory and a Lagrangian particle dispersion model to determine regional emissions. Our model-measurement framework incorporates emissions estimates from submodels for both anthropogenic and biological CO2 fluxes, and development of a CO2 concentration curtain at the boundary of the study region based on a combination of tower measurements and modeled vertical concentration gradients. We demonstrate that an emission inventory with high spatial and temporal resolution and the inclusion of urban biological fluxes are both essential to accurately modeling annual CO2 fluxes using surface measurement networks. We calculated annual average emissions in the Boston region of 0.92 kg C·m-2·y-1 (95% confidence interval: 0.79 to 1.06), which is 14% higher than the Anthropogenic Carbon Emissions System inventory. Based on the capability of the model-measurement approach demonstrated here, our framework should be able to detect changes in CO2 emissions of greater than 18%, providing stakeholders with critical information to assess mitigation efforts in Boston and surrounding areas.}, } @article {pmid29967153, year = {2018}, author = {Keedy, HE and Thomas, EN and Zaher, HS}, title = {Decoding on the ribosome depends on the structure of the mRNA phosphodiester backbone.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6731-E6740}, pmid = {29967153}, issn = {1091-6490}, support = {R01 GM112641/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell-Free System/chemistry/metabolism ; *Nucleic Acid Conformation ; Peptide Elongation Factor Tu/*chemistry/metabolism ; *Protein Biosynthesis ; RNA, Messenger/*chemistry/metabolism ; RNA, Transfer/*chemistry/metabolism ; Ribosomes/*chemistry/metabolism ; Static Electricity ; }, abstract = {During translation, the ribosome plays an active role in ensuring that mRNA is decoded accurately and rapidly. Recently, biochemical studies have also implicated certain accessory factors in maintaining decoding accuracy. However, it is currently unclear whether the mRNA itself plays an active role in the process beyond its ability to base pair with the tRNA. Structural studies revealed that the mRNA kinks at the interface of the P and A sites. A magnesium ion appears to stabilize this structure through electrostatic interactions with the phosphodiester backbone of the mRNA. Here we examined the role of the kink structure on decoding using a well-defined in vitro translation system. Disruption of the kink structure through site-specific phosphorothioate modification resulted in an acute hyperaccurate phenotype. We measured rates of peptidyl transfer for near-cognate tRNAs that were severely diminished and in some instances were almost 100-fold slower than unmodified mRNAs. In contrast to peptidyl transfer, the modifications had little effect on GTP hydrolysis by elongation factor thermal unstable (EF-Tu), suggesting that only the proofreading phase of tRNA selection depends critically on the kink structure. Although the modifications appear to have no effect on typical cognate interactions, peptidyl transfer for a tRNA that uses atypical base pairing is compromised. These observations suggest that the kink structure is important for decoding in the absence of Watson-Crick or G-U wobble base pairing at the third position. Our findings provide evidence for a previously unappreciated role for the mRNA backbone in ensuring uniform decoding of the genetic code.}, } @article {pmid29967152, year = {2018}, author = {Rudd, AK and Devaraj, NK}, title = {Traceless synthesis of ceramides in living cells reveals saturation-dependent apoptotic effects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7485-7490}, pmid = {29967152}, issn = {1091-6490}, support = {DP2 DK111801/DK/NIDDK NIH HHS/United States ; T32 CA009523/CA/NCI NIH HHS/United States ; }, mesh = {*Apoptosis ; Ceramides/*biosynthesis ; HeLa Cells ; Humans ; }, abstract = {Mammalian cells synthesize thousands of distinct lipids, yet the function of many of these lipid species is unknown. Ceramides, a class of sphingolipid, are implicated in several cell-signaling pathways but poor cell permeability and lack of selectivity in endogenous synthesis pathways have hampered direct study of their effects. Here we report a strategy that overcomes the inherent biological limitations of ceramide delivery by chemoselectively ligating lipid precursors in vivo to yield natural ceramides in a traceless manner. Using this method, we uncovered the apoptotic effects of several ceramide species and observed differences in their apoptotic activity based on acyl-chain saturation. Additionally, we demonstrate spatiotemporally controlled ceramide synthesis in live cells through photoinitiated lipid ligation. Our in situ lipid ligation approach addresses the long-standing problem of lipid-specific delivery and enables the direct study of unique ceramide species in live cells.}, } @article {pmid29967151, year = {2018}, author = {Miglianico, M and Eldering, M and Slater, H and Ferguson, N and Ambrose, P and Lees, RS and Koolen, KMJ and Pruzinova, K and Jancarova, M and Volf, P and Koenraadt, CJM and Duerr, HP and Trevitt, G and Yang, B and Chatterjee, AK and Wisler, J and Sturm, A and Bousema, T and Sauerwein, RW and Schultz, PG and Tremblay, MS and Dechering, KJ}, title = {Repurposing isoxazoline veterinary drugs for control of vector-borne human diseases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6920-E6926}, pmid = {29967151}, issn = {1091-6490}, mesh = {Animals ; Communicable Disease Control/*methods ; Culicidae/*growth & development ; Humans ; Insecticides/*pharmacology ; Mosquito Control/*methods ; Mosquito Vectors/*growth & development ; Psychodidae/*growth & development ; }, abstract = {Isoxazolines are oral insecticidal drugs currently licensed for ectoparasite control in companion animals. Here we propose their use in humans for the reduction of vector-borne disease incidence. Fluralaner and afoxolaner rapidly killed Anopheles, Aedes, and Culex mosquitoes and Phlebotomus sand flies after feeding on a drug-supplemented blood meal, with IC50 values ranging from 33 to 575 nM, and were fully active against strains with preexisting resistance to common insecticides. Based on allometric scaling of preclinical pharmacokinetics data, we predict that a single human median dose of 260 mg (IQR, 177-407 mg) for afoxolaner, or 410 mg (IQR, 278-648 mg) for fluralaner, could provide an insecticidal effect lasting 50-90 days against mosquitoes and Phlebotomus sand flies. Computational modeling showed that seasonal mass drug administration of such a single dose to a fraction of a regional population would dramatically reduce clinical cases of Zika and malaria in endemic settings. Isoxazolines therefore represent a promising new component of drug-based vector control.}, } @article {pmid29967150, year = {2018}, author = {Chong, YE and Guo, M and Yang, XL and Kuhle, B and Naganuma, M and Sekine, SI and Yokoyama, S and Schimmel, P}, title = {Distinct ways of G:U recognition by conserved tRNA binding motifs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7527-7532}, pmid = {29967150}, issn = {1091-6490}, support = {R01 GM015539/GM/NIGMS NIH HHS/United States ; R01 GM023562/GM/NIGMS NIH HHS/United States ; }, mesh = {Alanine-tRNA Ligase/*chemistry/genetics ; Escherichia coli/*chemistry/genetics ; Escherichia coli Proteins/*chemistry/genetics ; Humans ; *Models, Molecular ; Mutation ; *Nucleotide Motifs ; RNA, Transfer/*chemistry/genetics ; }, abstract = {Throughout three domains of life, alanyl-tRNA synthetases (AlaRSs) recognize a G3:U70 base pair in the acceptor stem of tRNAAla as the major identity determinant of tRNAAla The crystal structure of the archaeon Archaeoglobus fulgidus AlaRS in complex with tRNAAla provided the basis for G3:U70 recognition with residues (Asp and Asn) that are conserved in the three domains [Naganuma M, et al. (2014) Nature 510:507-511]. The recognition mode is unprecedented, with specific accommodation of the dyad asymmetry of the G:U wobble pair and exclusion of the dyad symmetry of a Watson-Crick pair. With this conserved mode, specificity is based more on "fit" than on direct recognition of specific atomic groups. Here, we show that, in contrast to the archaeal complex, the Escherichia coli enzyme uses direct positive (energetically favorable) minor groove recognition of the unpaired 2-amino of G3 by Asp and repulsion of a competing base pair by Asn. Strikingly, mutations that disrupted positive recognition by the E. coli enzyme had little or no effect on G:U recognition by the human enzyme. Alternatively, Homo sapiens AlaRS selects G:U without positive recognition and uses Asp instead to repel a competitor. Thus, the widely conserved Asp-plus-Asn architecture of AlaRSs can select G:U in a straightforward (bacteria) or two different unconventional (eukarya/archaea) ways. The adoption of different modes for recognition of a widely conserved G:U pair in alanine tRNAs suggests an early and insistent role for G:U in the development of the genetic code.}, } @article {pmid29967149, year = {2018}, author = {Fedorov, LA and Chang, DS and Giese, MA and Bülthoff, HH and de la Rosa, S}, title = {Adaptation aftereffects reveal representations for encoding of contingent social actions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7515-7520}, pmid = {29967149}, issn = {1091-6490}, mesh = {*Adaptation, Psychological ; Female ; Humans ; Male ; *Social Behavior ; }, abstract = {A hallmark of human social behavior is the effortless ability to relate one's own actions to that of the interaction partner, e.g., when stretching out one's arms to catch a tripping child. What are the behavioral properties of the neural substrates that support this indispensable human skill? Here we examined the processes underlying the ability to relate actions to each other, namely the recognition of spatiotemporal contingencies between actions (e.g., a "giving" that is followed by a "taking"). We used a behavioral adaptation paradigm to examine the response properties of perceptual mechanisms at a behavioral level. In contrast to the common view that action-sensitive units are primarily selective for one action (i.e., primary action, e.g., 'throwing"), we demonstrate that these processes also exhibit sensitivity to a matching contingent action (e.g., "catching"). Control experiments demonstrate that the sensitivity of action recognition processes to contingent actions cannot be explained by lower-level visual features or amodal semantic adaptation. Moreover, we show that action recognition processes are sensitive only to contingent actions, but not to noncontingent actions, demonstrating their selective sensitivity to contingent actions. Our findings show the selective coding mechanism for action contingencies by action-sensitive processes and demonstrate how the representations of individual actions in social interactions can be linked in a unified representation.}, } @article {pmid29967148, year = {2018}, author = {Olson, ME and Soriano, D and Rosell, JA and Anfodillo, T and Donoghue, MJ and Edwards, EJ and León-Gómez, C and Dawson, T and Camarero Martínez, JJ and Castorena, M and Echeverría, A and Espinosa, CI and Fajardo, A and Gazol, A and Isnard, S and Lima, RS and Marcati, CR and Méndez-Alonzo, R}, title = {Plant height and hydraulic vulnerability to drought and cold.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7551-7556}, pmid = {29967148}, issn = {1091-6490}, mesh = {*Acclimatization ; *Cold Temperature ; Dehydration ; Magnoliopsida/*growth & development ; *Tundra ; }, abstract = {Understanding how plants survive drought and cold is increasingly important as plants worldwide experience dieback with drought in moist places and grow taller with warming in cold ones. Crucial in plant climate adaptation are the diameters of water-transporting conduits. Sampling 537 species across climate zones dominated by angiosperms, we find that plant size is unambiguously the main driver of conduit diameter variation. And because taller plants have wider conduits, and wider conduits within species are more vulnerable to conduction-blocking embolisms, taller conspecifics should be more vulnerable than shorter ones, a prediction we confirm with a plantation experiment. As a result, maximum plant size should be short under drought and cold, which cause embolism, or increase if these pressures relax. That conduit diameter and embolism vulnerability are inseparably related to plant size helps explain why factors that interact with conduit diameter, such as drought or warming, are altering plant heights worldwide.}, } @article {pmid29967147, year = {2018}, author = {Stanish, C and Tantaleán, H and Knudson, K}, title = {Feasting and the evolution of cooperative social organizations circa 2300 B.P. in Paracas culture, southern Peru.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6716-E6721}, pmid = {29967147}, issn = {1091-6490}, abstract = {Recent theoretical innovations in cultural evolutionary theory emphasize the role of cooperative social organizations that unite diverse groups as a key step in the evolution of social complexity. A principal mechanism identified by this theory is feasting, a strategy that reinforces norms of cooperation. Feasts occur throughout the premodern world, and the intensification of feasting is empirically correlated to increased social complexity. A critical factor in assessing the evolutionary significance of this practice is the scale and range of the feast from that focused on a single community to ones that draw from a large region or catchment zone. This work addresses the degree to which hosts draw on a local area vs. a regional one in initial prehistoric feasting. We report on excavations at a locus of intensive feasting-a ceremonial sunken court-in a fifth- to third-century BCE Paracas site on the south coast of Peru. We selected 39 organic objects from the court placed as offerings during major feasting episodes. We analyzed the radiogenic strontium isotope (87Sr/86Sr) values to determine the geographical origin of each object. The 87Sr/86Sr data plus additional archaeological data support a hypothesis that the catchment of the court was quite extensive. The initial strategy of political and economic alliance building was macroregional in scope. These data indicate that the most effective initial strategy in early state formation in this case study was to build wide alliances at the outset, as opposed to first consolidating local ones that subsequently expand.}, } @article {pmid29967146, year = {2018}, author = {Ahmed, F}, title = {QnAs with Shaul Mukamel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7452-7453}, pmid = {29967146}, issn = {1091-6490}, } @article {pmid29967145, year = {2018}, author = {Zhou, J and Zeng, Y and Cui, L and Chen, X and Stauffer, S and Wang, Z and Yu, F and Lele, SM and Talmon, GA and Black, AR and Chen, Y and Dong, J}, title = {Zyxin promotes colon cancer tumorigenesis in a mitotic phosphorylation-dependent manner and through CDK8-mediated YAP activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6760-E6769}, pmid = {29967145}, issn = {1091-6490}, support = {P30 CA036727/CA/NCI NIH HHS/United States ; P30 GM106397/GM/NIGMS NIH HHS/United States ; R01 GM109066/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Animals ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/*metabolism/pathology ; Colonic Neoplasms/genetics/*metabolism/pathology ; Cyclin-Dependent Kinase 8/genetics/*metabolism ; Female ; Humans ; Male ; Mice ; Mice, Knockout ; Mice, Nude ; *Mitosis ; Neoplasm Proteins/genetics/*metabolism ; Phosphoproteins/genetics/*metabolism ; Phosphorylation/genetics ; Zyxin/*biosynthesis/genetics ; }, abstract = {Zyxin is a member of the focal adhesion complex and plays a critical role in actin filament polymerization and cell motility. Several recent studies showed that Zyxin is a positive regulator of Yki/YAP (Yes-associated protein) signaling. However, little is known about the mechanisms by which Zyxin itself is regulated and how Zyxin affects Hippo-YAP activity. We first showed that Zyxin is phosphorylated by CDK1 during mitosis. Depletion of Zyxin resulted in significantly impaired colon cancer cell proliferation, migration, anchorage-independent growth, and tumor formation in xenograft animal models. Mitotic phosphorylation is required for Zyxin activity in promoting growth. Zyxin regulates YAP activity through the colon cancer oncogene CDK8. CDK8 knockout phenocopied Zyxin knockdown in colon cancer cells, while ectopic expression of CDK8 substantially restored the tumorigenic defects of Zyxin-depletion cells. Mechanistically, we showed that CDK8 directly phosphorylated YAP and promoted its activation. Fully activated YAP is required to support the growth in CDK8-knockout colon cancer cells in vitro and in vivo. Together, these observations suggest that Zyxin promotes colon cancer tumorigenesis in a mitotic-phosphorylation-dependent manner and through CDK8-mediated YAP activation.}, } @article {pmid29967144, year = {2018}, author = {Otto, CRV and Zheng, H and Gallant, AL and Iovanna, R and Carlson, BL and Smart, MD and Hyberg, S}, title = {Past role and future outlook of the Conservation Reserve Program for supporting honey bees in the Great Plains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7629-7634}, pmid = {29967144}, issn = {1091-6490}, mesh = {Animals ; *Beekeeping ; *Bees ; *Conservation of Natural Resources ; *Ecosystem ; North Dakota ; South Dakota ; }, abstract = {Human dependence on insect pollinators continues to grow even as pollinators face global declines. The Northern Great Plains (NGP), a region often referred to as America's last honey bee (Apis mellifera) refuge, has undergone rapid land-cover change due to cropland expansion and weakened land conservation programs. We conducted a trend analysis and estimated conversion rates of Conservation Reserve Program (CRP) enrollments around bee apiaries from 2006 to 2016 and developed models to identify areas of habitat loss. Our analysis revealed that NGP apiaries lost over 53% of lands enrolled in the CRP, and the rate of loss was highest in areas of high apiary density. We estimated over 163,000 ha of CRP lands in 2006 within 1.6 km of apiaries was converted to row crops by 2012. We also evaluated how alternative scenarios of future CRP acreage caps may affect habitat suitability for supporting honey bee colonies. Our scenario revealed that a further reduction in CRP lands to 7.7 million ha nationally would reduce the number of apiaries in the NGP that meet defined forage criteria by 28% on average. Alternatively, increasing the national cap to 15 million ha would increase the number of NGP apiaries that meet defined forage criteria by 155%. Our scenarios also show that strategic placement of CRP lands near existing apiaries increased the number of apiaries that meet forage criteria by 182%. Our research will be useful for informing the potential consequences of future US farm bill policy and land management in the epicenter of the US beekeeping industry.}, } @article {pmid29967143, year = {2018}, author = {Zeng, M and Kim, YY and Anduix-Canto, C and Frontera, C and Laundy, D and Kapur, N and Christenson, HK and Meldrum, FC}, title = {Confinement generates single-crystal aragonite rods at room temperature.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7670-7675}, pmid = {29967143}, issn = {1091-6490}, abstract = {The topic of calcite and aragonite polymorphism attracts enormous interest from fields including biomineralization and paleogeochemistry. While aragonite is only slightly less thermodynamically stable than calcite under ambient conditions, it typically only forms as a minor product in additive-free solutions at room temperature. However, aragonite is an abundant biomineral, and certain organisms can selectively generate calcite and aragonite. This fascinating behavior has been the focus of decades of research, where this has been driven by a search for specific organic macromolecules that can generate these polymorphs. However, despite these efforts, we still have a poor understanding of how organisms achieve such selectivity. In this work, we consider an alternative possibility and explore whether the confined volumes in which all biomineralization occurs could also influence polymorph. Calcium carbonate was precipitated within the cylindrical pores of track-etched membranes, where these enabled us to systematically investigate the relationship between the membrane pore diameter and polymorph formation. Aragonite was obtained in increasing quantities as the pore size was reduced, such that oriented single crystals of aragonite were the sole product from additive-free solutions in 25-nm pores and significant quantities of aragonite formed in pores as large as 200 nm in the presence of low concentrations of magnesium and sulfate ions. This effect can be attributed to the effect of the pore size on the ion distribution, which becomes of increasing importance in small pores. These intriguing results suggest that organisms may exploit confinement effects to gain control over crystal polymorph.}, } @article {pmid29967142, year = {2018}, author = {Shwab, EK and Saraf, P and Zhu, XQ and Zhou, DH and McFerrin, BM and Ajzenberg, D and Schares, G and Hammond-Aryee, K and van Helden, P and Higgins, SA and Gerhold, RW and Rosenthal, BM and Zhao, X and Dubey, JP and Su, C}, title = {Human impact on the diversity and virulence of the ubiquitous zoonotic parasite Toxoplasma gondii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6956-E6963}, pmid = {29967142}, issn = {1091-6490}, mesh = {Animals ; Cats ; Human Migration ; Humans ; Mice ; South America ; Toxoplasma/*genetics/*pathogenicity ; Toxoplasmosis/*genetics/mortality/*transmission ; Zoonoses/*genetics/mortality/*transmission ; }, abstract = {A majority of emerging infectious diseases in humans are zoonoses. Understanding factors that influence the emergence and transmission of zoonoses is pivotal for their prevention and control. Toxoplasma gondii is one of the most widespread zoonotic pathogens known today. Whereas only a few genotypes of T. gondii dominate in the Northern Hemisphere, many genotypes coexist in South America. Furthermore, T. gondii strains from South America are more likely to be virulent than those from the Northern Hemisphere. However, it is not clear what factor(s) shaped modern-day genetic diversity and virulence of T. gondii Here, our analysis suggests that the rise and expansion of farming in the past 11,000 years established the domestic cat/mouse transmission cycle for T. gondii, which has undoubtedly played a significant role in the selection of certain linages of T. gondii Our mathematical simulations showed that within the domestic transmission cycle, intermediately mouse-virulent T. gondii genotypes have an adaptive advantage and eventually become dominant due to a balance between lower host mortality and the ability to superinfect mice previously infected with a less virulent T. gondii strain. Our analysis of the global type II lineage of T. gondii suggests its Old World origin but recent expansion in North America, which is likely the consequence of global human migration and trading. These results have significant implications concerning transmission and evolution of zoonotic pathogens in the rapidly expanding anthropized environment demanded by rapid growth of the human population and intensive international trading at present and in the future.}, } @article {pmid29967141, year = {2018}, author = {Morgan, MG and Abdulla, A and Ford, MJ and Rath, M}, title = {US nuclear power: The vanishing low-carbon wedge.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7184-7189}, pmid = {29967141}, issn = {1091-6490}, abstract = {Nuclear power holds the potential to make a significant contribution to decarbonizing the US energy system. Whether it could do so in its current form is a critical question: Existing large light water reactors in the United States are under economic pressure from low natural gas prices, and some have already closed. Moreover, because of their great cost and complexity, it appears most unlikely that any new large plants will be built over the next several decades. While advanced reactor designs are sometimes held up as a potential solution to nuclear power's challenges, our assessment of the advanced fission enterprise suggests that no US design will be commercialized before midcentury. That leaves factory-manufactured, light water small modular reactors (SMRs) as the only option that might be deployed at significant scale in the climate-critical period of the next several decades. We have systematically investigated how a domestic market could develop to support that industry over the next several decades and, in the absence of a dramatic change in the policy environment, have been unable to make a convincing case. Achieving deep decarbonization of the energy system will require a portfolio of every available technology and strategy we can muster. It should be a source of profound concern for all who care about climate change that, for entirely predictable and resolvable reasons, the United States appears set to virtually lose nuclear power, and thus a wedge of reliable and low-carbon energy, over the next few decades.}, } @article {pmid29967140, year = {2018}, author = {Smithey, MJ and Venturi, V and Davenport, MP and Buntzman, AS and Vincent, BG and Frelinger, JA and Nikolich-Žugich, J}, title = {Lifelong CMV infection improves immune defense in old mice by broadening the mobilized TCR repertoire against third-party infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6817-E6825}, pmid = {29967140}, issn = {1091-6490}, support = {P30 CA023074/CA/NCI NIH HHS/United States ; R01 AG048021/AG/NIA NIH HHS/United States ; U54 AI081680/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Cytomegalovirus Infections/*immunology/pathology ; *Immunity, Cellular ; Listeria monocytogenes/*immunology ; Listeriosis/*immunology/pathology ; Male ; Mice ; Muromegalovirus/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/*immunology ; }, abstract = {Lifelong interactions between host and the ubiquitous and persistent cytomegalovirus (CMV) have been proposed to contribute to the age-related decline in immunity. Prior work from us and others found some support for that idea, yet evidence that this led to increased vulnerability to other infections was not obtained. Moreover, evidence has accumulated that CMV infection can be beneficial to immune defense in young/adult mice and humans, dominantly via enhanced innate immunity. Here, we describe an unexpected impact of murine CMV (MCMV) upon the T cell response of old mice to Listeria monocytogenes expressing the model antigen, OVA (Lm-OVA). Single-cell sequencing of the OVA-specific CD8 T cell receptor β (TCRβ) repertoire of old mice demonstrated that old MCMV-infected mice recruited many diverse clonotypes that afforded broad and often more efficient recognition of antigenic peptide variants. This stood in contrast to old control mice, which exhibited strong narrowing and homogenization of the elicited repertoire. High-throughput sequencing of the total naïve CD8 TCRβ repertoire showed that many of these diverse OVA-specific clonotypes were present in the naïve CD8 repertoire of mice in all groups (adult, old control, and old MCMV+) yet were only recruited into the Lm-OVA response in MCMV+ old mice. These results have profound implications for our understanding of T cell immunity over a life span and suggest that our coevolution with CMV may include surprising, potentially positive impacts on adaptive heterologous immunity in late life.}, } @article {pmid29967139, year = {2018}, author = {Abe, KI and Funaya, S and Tsukioka, D and Kawamura, M and Suzuki, Y and Suzuki, MG and Schultz, RM and Aoki, F}, title = {Minor zygotic gene activation is essential for mouse preimplantation development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6780-E6788}, pmid = {29967139}, issn = {1091-6490}, support = {R01 HD022681/HD/NICHD NIH HHS/United States ; R37 HD022681/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Blastocyst/cytology/*metabolism ; Dichlororibofuranosylbenzimidazole/pharmacology ; Embryonic Development/drug effects/*physiology ; Gene Expression Regulation, Developmental/drug effects/*physiology ; Histones/metabolism ; Mice ; Zygote/cytology/*metabolism ; }, abstract = {In mice, transcription initiates at the mid-one-cell stage and transcriptional activity dramatically increases during the two-cell stage, a process called zygotic gene activation (ZGA). Associated with ZGA is a marked change in the pattern of gene expression that occurs after the second round of DNA replication. To distinguish ZGA before and after the second-round DNA replication, the former and latter are called minor and major ZGA, respectively. Although major ZGA are required for development beyond the two-cell stage, the function of minor ZGA is not well understood. Transiently inhibiting minor ZGA with 5, 6-dichloro-1-β-d-ribofuranosyl-benzimidazole (DRB) resulted in the majority of embryos arresting at the two-cell stage and retention of the H3K4me3 mark that normally decreases. After release from DRB, at which time major ZGA normally occurred, transcription initiated with characteristics of minor ZGA but not major ZGA, although degradation of maternal mRNA normally occurred. Thus, ZGA occurs sequentially starting with minor ZGA that is critical for the maternal-to-zygotic transition.}, } @article {pmid29967138, year = {2018}, author = {Hauser, DDW and Laidre, KL and Stern, HL}, title = {Vulnerability of Arctic marine mammals to vessel traffic in the increasingly ice-free Northwest Passage and Northern Sea Route.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7617-7622}, pmid = {29967138}, issn = {1091-6490}, mesh = {*Animal Migration ; Animals ; Arctic Regions ; *Climate Change ; *Ships ; Ursidae/*physiology ; Whales/*physiology ; }, abstract = {The fabled Northwest Passage and Northern Sea Route that were once the quests of early Western explorers are now increasingly sea ice-free, with routine vessel transits expected by midcentury. The potential impacts of this novel vessel traffic on endemic Arctic marine mammal (AMM) species are unknown despite their critical social and ecological roles in the ecosystem and widely recognized susceptibility to ice loss. We developed a vulnerability assessment of 80 subpopulations of seven AMM species to vessel traffic during the ice-free season. Vulnerability scores were based on the combined influence of spatially explicit exposure to the sea routes and a suite of sensitivity variables. More than half of AMM subpopulations (42/80) are exposed to open-water vessel transits in the Arctic sea routes. Narwhals (Monodon monoceros) were estimated to be most vulnerable to vessel impacts, given their high exposure and sensitivity, and polar bears (Ursus maritimus) were estimated to be the least vulnerable because of their low exposure and sensitivity. Regions with geographic bottlenecks, such as the Bering Strait and eastern Canadian Arctic, were characterized by two to three times higher vulnerability than more remote regions. These pinch points are obligatory pathways for both vessels and migratory AMMs, and so represent potentially high conflict areas but also opportunities for conservation-informed planning. Some of the species and regions identified as least vulnerable were also characterized by high uncertainty, highlighting additional data and monitoring needs. Our quantification of the heterogeneity of risk across AMM species provides a necessary first step toward developing best practices for maritime industries poised to advance into this rapidly changing seascape.}, } @article {pmid29967137, year = {2018}, author = {Shao, J and Wang, M and Yu, G and Zhu, S and Yu, Y and Heng, BC and Wu, J and Ye, H}, title = {Synthetic far-red light-mediated CRISPR-dCas9 device for inducing functional neuronal differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6722-E6730}, pmid = {29967137}, issn = {1091-6490}, mesh = {Basic Helix-Loop-Helix Transcription Factors/*biosynthesis/genetics ; *CRISPR-Cas Systems ; *Cell Differentiation ; *Cellular Reprogramming ; *Epigenesis, Genetic ; HEK293 Cells ; HeLa Cells ; Humans ; *Light ; Nerve Tissue Proteins/*biosynthesis/genetics ; Neurons/cytology/*metabolism ; Optogenetics/methods ; Synthetic Biology ; }, abstract = {The ability to control the activity of CRISPR-dCas9 with precise spatiotemporal resolution will enable tight genome regulation of user-defined endogenous genes for studying the dynamics of transcriptional regulation. Optogenetic devices with minimal phototoxicity and the capacity for deep tissue penetration are extremely useful for precise spatiotemporal control of cellular behavior and for future clinic translational research. Therefore, capitalizing on synthetic biology and optogenetic design principles, we engineered a far-red light (FRL)-activated CRISPR-dCas9 effector (FACE) device that induces transcription of exogenous or endogenous genes in the presence of FRL stimulation. This versatile system provides a robust and convenient method for precise spatiotemporal control of endogenous gene expression and also has been demonstrated to mediate targeted epigenetic modulation, which can be utilized to efficiently promote differentiation of induced pluripotent stem cells into functional neurons by up-regulating a single neural transcription factor, NEUROG2 This FACE system might facilitate genetic/epigenetic reprogramming in basic biological research and regenerative medicine for future biomedical applications.}, } @article {pmid29967136, year = {2018}, author = {Mestre, M and Ruiz-González, C and Logares, R and Duarte, CM and Gasol, JM and Sala, MM}, title = {Sinking particles promote vertical connectivity in the ocean microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6799-E6807}, pmid = {29967136}, issn = {1091-6490}, mesh = {Microbiota/*physiology ; *Models, Biological ; Oceans and Seas ; *Water Microbiology ; }, abstract = {The sinking of organic particles formed in the photic layer is a main vector of carbon export into the deep ocean. Although sinking particles are heavily colonized by microbes, so far it has not been explored whether this process plays a role in transferring prokaryotic diversity from surface to deep oceanic layers. Using Illumina sequencing of the 16S rRNA gene, we explore here the vertical connectivity of the ocean microbiome by characterizing marine prokaryotic communities associated with five different size fractions and examining their compositional variability from surface down to 4,000 m across eight stations sampled in the Atlantic, Pacific, and Indian Oceans during the Malaspina 2010 Expedition. Our results show that the most abundant prokaryotes in the deep ocean are also present in surface waters. This vertical community connectivity seems to occur predominantly through the largest particles because communities in the largest size fractions showed the highest taxonomic similarity throughout the water column, whereas free-living communities were more isolated vertically. Our results further suggest that particle colonization processes occurring in surface waters determine to some extent the composition and biogeography of bathypelagic communities. Overall, we postulate that sinking particles function as vectors that inoculate viable particle-attached surface microbes into the deep-sea realm, determining to a considerable extent the structure, functioning, and biogeography of deep ocean communities.}, } @article {pmid29967135, year = {2018}, author = {Chan, HF and Zhao, R and Parada, GA and Meng, H and Leong, KW and Griffith, LG and Zhao, X}, title = {Folding artificial mucosa with cell-laden hydrogels guided by mechanics models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7503-7508}, pmid = {29967135}, issn = {1091-6490}, mesh = {Cell Line, Tumor ; Epithelial Cells/cytology/*metabolism ; Humans ; Hydrogels/*chemistry ; *Models, Biological ; Mucous Membrane/cytology/metabolism ; *Tissue Engineering ; }, abstract = {The surfaces of many hollow or tubular tissues/organs in our respiratory, gastrointestinal, and urogenital tracts are covered by mucosa with folded patterns. The patterns are induced by mechanical instability of the mucosa under compression due to constrained growth. Recapitulating this folding process in vitro will facilitate the understanding and engineering of mucosa in various tissues/organs. However, scant attention has been paid to address the challenge of reproducing mucosal folding. Here we mimic the mucosal folding process using a cell-laden hydrogel film attached to a prestretched tough-hydrogel substrate. The cell-laden hydrogel constitutes a human epithelial cell lining on stromal component to recapitulate the physiological feature of a mucosa. Relaxation of the prestretched tough-hydrogel substrate applies compressive strains on the cell-laden hydrogel film, which undergoes mechanical instability and evolves into morphological patterns. We predict the conditions for mucosal folding as well as the morphology of and strain in the folded artificial mucosa using a combination of theory and simulation. The work not only provides a simple method to fold artificial mucosa but also demonstrates a paradigm in tissue engineering via harnessing mechanical instabilities guided by quantitative mechanics models.}, } @article {pmid29967011, year = {2018}, author = {Mamajiwalla, S}, title = {A Career in Patent Law: At the Cutting Edge of Science, but Not at the Bench.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a032920}, pmid = {29967011}, issn = {1943-0264}, abstract = {Patent law is an area that many people move into after obtaining a PhD in biomedical science. Close to the cutting edge of research, patent agents draft detailed descriptions of new biotechnology inventions required for patent applications and engage with patent offices during the review process known as patent prosecution. Jobs are also available as patent examiners who examine these patent applications, and it is common for individuals to move between the two jobs. A law firm is generally the best place to train as a patent agent, but biotech companies and tech-transfer offices can provide an alternative route. Although obtaining a law degree is not essential after your PhD, it is recommended, and all patent agents must pass rigorous qualifying exams. Further down the road, training in patent law offers opportunities for in-house work in biotech companies, business development, and mergers and acquisitions.}, } @article {pmid29967010, year = {2018}, author = {Kwok, CK and Marsico, G and Balasubramanian, S}, title = {Detecting RNA G-Quadruplexes (rG4s) in the Transcriptome.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a032284}, pmid = {29967010}, issn = {1943-0264}, abstract = {RNA G-quadruplex (rG4) secondary structures are proposed to play key roles in fundamental biological processes that include the modulation of transcriptional, co-transcriptional, and posttranscriptional events. Recent methodological developments that include predictive algorithms and structure-based sequencing have enabled the detection and mapping of rG4 structures on a transcriptome-wide scale at high sensitivity and resolution. The data generated by these studies provide valuable insights into the potentially diverse roles of rG4s in biology and open up a number of mechanistic hypotheses. Herein we highlight these methodologies and discuss the associated findings in relation to rG4-related biological mechanisms.}, } @article {pmid29967009, year = {2018}, author = {Pollard, TD and Goldman, RD}, title = {Overview of the Cytoskeleton from an Evolutionary Perspective.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a030288}, pmid = {29967009}, issn = {1943-0264}, abstract = {SUMMARYOrganisms in the three domains of life depend on protein polymers to form a cytoskeleton that helps to establish their shapes, maintain their mechanical integrity, divide, and, in many cases, move. Eukaryotes have the most complex cytoskeletons, comprising three cytoskeletal polymers-actin filaments, intermediate filaments, and microtubules-acted on by three families of motor proteins (myosin, kinesin, and dynein). Prokaryotes have polymers of proteins homologous to actin and tubulin but no motors, and a few bacteria have a protein related to intermediate filament proteins.}, } @article {pmid29966686, year = {2018}, author = {Wood, HM and González, VL and Lloyd, M and Coddington, J and Scharff, N}, title = {Next-generation museum genomics: Phylogenetic relationships among palpimanoid spiders using sequence capture techniques (Araneae: Palpimanoidea).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {907-918}, doi = {10.1016/j.ympev.2018.06.038}, pmid = {29966686}, issn = {1095-9513}, abstract = {Historical museum specimens are invaluable for morphological and taxonomic research, but typically the DNA is degraded making traditional sequencing techniques difficult to impossible for many specimens. Recent advances in Next-Generation Sequencing, specifically target capture, makes use of short fragment sizes typical of degraded DNA, opening up the possibilities for gathering genomic data from museum specimens. This study uses museum specimens and recent target capture sequencing techniques to sequence both Ultra-Conserved Elements (UCE) and exonic regions for lineages that span the modern spiders, Araneomorphae, with a focus on Palpimanoidea. While many previous studies have used target capture techniques on dried museum specimens (for example, skins, pinned insects), this study includes specimens that were collected over the last two decades and stored in 70% ethanol at room temperature. Our findings support the utility of target capture methods for examining deep relationships within Araneomorphae: sequences from both UCE and exonic loci were important for resolving relationships; a monophyletic Palpimanoidea was recovered in many analyses and there was strong support for family and generic-level palpimanoid relationships. Ancestral character state reconstructions reveal that the highly modified carapace observed in mecysmaucheniids and archaeids has evolved independently.}, } @article {pmid29966604, year = {2018}, author = {Baldeosingh, R and Gao, H and Wu, X and Fossett, N}, title = {Hedgehog signaling from the Posterior Signaling Center maintains U-shaped expression and a prohemocyte population in Drosophila.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {132-145}, pmid = {29966604}, issn = {1095-564X}, support = {R01 DK072229/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Gene Expression Regulation/*physiology ; Hedgehog Proteins/genetics/*metabolism ; Hematopoiesis/*physiology ; Hematopoietic Stem Cells/cytology/*metabolism ; Hemocytes/cytology/*metabolism ; Signal Transduction/*physiology ; }, abstract = {Hematopoietic progenitor choice between multipotency and differentiation is tightly regulated by intrinsic factors and extrinsic signals from the surrounding microenvironment. The Drosophila melanogaster hematopoietic lymph gland has emerged as a powerful tool to investigate mechanisms that regulate hematopoietic progenitor choice in vivo. The lymph gland contains progenitor cells, which share key characteristics with mammalian hematopoietic progenitors such as quiescence, multipotency and niche-dependence. The lymph gland is zonally arranged, with progenitors located in medullary zone, differentiating cells in the cortical zone, and the stem cell niche or Posterior Signaling Center (PSC) residing at the base of the medullary zone (MZ). This arrangement facilitates investigations into how signaling from the microenvironment controls progenitor choice. The Drosophila Friend of GATA transcriptional regulator, U-shaped, is a conserved hematopoietic regulator. To identify additional novel intrinsic and extrinsic regulators that interface with U-shaped to control hematopoiesis, we conducted an in vivo screen for factors that genetically interact with u-shaped. Smoothened, a downstream effector of Hedgehog signaling, was one of the factors identified in the screen. Here we report our studies that characterized the relationship between Smoothened and U-shaped. We showed that the PSC and Hedgehog signaling are required for U-shaped expression and that U-shaped is an important intrinsic progenitor regulator. These observations identify a potential link between the progenitor regulatory machinery and extrinsic signals from the PSC. Furthermore, we showed that both Hedgehog signaling and the PSC are required to maintain a subpopulation of progenitors. This led to a delineation of PSC-dependent versus PSC-independent progenitors and provided further evidence that the MZ progenitor population is heterogeneous. Overall, we have identified a connection between a conserved hematopoietic master regulator and a putative stem cell niche, which adds to our understanding of how signals from the microenvironment regulate progenitor multipotency.}, } @article {pmid29966527, year = {2018}, author = {Patel, D and Patel, M and Westermark, B and Singh, U}, title = {Dynamic bimodal changes in CpG and non-CpG methylation genome-wide upon CGGBP1 loss-of-function.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {419}, pmid = {29966527}, issn = {1756-0500}, mesh = {*CpG Islands ; Cytosine ; *DNA Methylation ; DNA-Binding Proteins/*genetics ; Genome ; Humans ; Loss of Function Mutation ; Promoter Regions, Genetic ; Sequence Analysis, DNA ; }, abstract = {OBJECTIVES: Although CpG methylation is well studied, mechanisms of non-CpG methylation in mammals remains elusive. Studying proteins with non-CpG cytosine methylation-sensitive DNA-binding, such as human CGGBP1, can unveil cytosine methylation regulatory mechanisms. Here we have resequenced a published genome-wide bisulfite sequencing library and analyzed it at base level resolution. CpG, CHG and CHH (where H is any nucleotide other than G) methylation states in non-targeting or CGGBP1-targeting shmiR lentivirus-transduced cells have been analyzed to identify how CGGBP1 regulates CpG and non-CpG methylation.

RESULTS: We report that CGGBP1 acts as a dynamic bimodal balancer of methylation. Both gain and loss of methylation observed upon CGGBP1 depletion were spatially overlapping at annotated functional regions and not identifiable with any sequence motifs but clearly associated with GC-skew. CGGBP1 depletion caused clustered methylation changes in cis, upstream of R-loop forming promoters. This was complemented by clustered occurrences of methylation changes in proximity of transcription start sites of known cytosine methylation regulatory genes, altered expression of which can regulate cytosine methylation in trans. Despite low coverage, our data provide reliable estimates of the spectrum of methylation changes regulated by CGGBP1 in all cytosine contexts genome-wide through a combination of cis and trans-acting mechanisms.}, } @article {pmid29966514, year = {2018}, author = {Pan, YJ and Lin, YC and Yu, BF and Zu, YG and Yu, F and Tang, ZH}, title = {Transcriptomics comparison reveals the diversity of ethylene and methyl-jasmonate in roles of TIA metabolism in Catharanthus roseus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {508}, pmid = {29966514}, issn = {1471-2164}, mesh = {ATP-Binding Cassette Transporters/genetics/metabolism ; Acetates/*pharmacology ; Biosynthetic Pathways/drug effects/genetics ; Catharanthus/*genetics/metabolism ; Cyclopentanes/*pharmacology ; Ethylenes/*pharmacology ; Gene Expression Regulation, Plant/drug effects/genetics ; Oxylipins/*pharmacology ; Plant Leaves/genetics/metabolism ; Plant Proteins/genetics/metabolism ; Plant Roots/genetics/metabolism ; Principal Component Analysis ; Secologanin Tryptamine Alkaloids/chemistry/*metabolism ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: The medicinal plant, Catharanthus roseus (C. roseus), accumulates a wide range of terpenoid indole alkaloids (TIAs). Ethylene (ET) and methyl-jasmonate (MeJA) were previously reported as effective elicitors for the production of various valuable secondary metabolites of C. roseus, while a few ET or MeJA induced transcriptomic research is yet reported on this species. In this study, the de-novo transcriptome assembly of C. roseus is performed by using the next-generation sequencing technology.

RESULTS: The result shows that phenolic biosynthesis genes respond specifically to ET in leaves, monoterpenoid biosynthesis genes respond specifically to MeJA in roots. By screening the database, 23 ATP-binding cassette (ABC) transporter partial sequences are identified in C. roseus. On this basis, more than 80 key genes that encode key enzymes (namely TIA pathway, transcriptional factor (TF) and candidate ABC transporter) of alkaloid synthesis in TIA biosynthetic pathways are chosen to explore the integrative responses to ET and MeJA at the transcriptional level. Our data indicated that TIA accumulation is strictly regulated by the TF ethylene responsive factor (ERF) and bHLH iridoid synthesis 1 (BIS1). The heatmap, combined with principal component analysis (PCA) of C. roseus, shows that ERF co-expression with ABC2 and ABC8 specific expression in roots affect the root-specific accumulation of vinblastine in C. roseus. On the contrast, BIS1 activities follow a similar pattern of ABC3 and CrTPT2 specific expression in leaves, which affects the leaf-specific accumulation of vindoline in C. roseus.

CONCLUSIONS: Results presented above illustrate that ethylene has a stronger effect than MeJA on TIA induction at both transcriptional and metabolite level. Furthermore, meta-analysis reveals that ERF and BIS1 form a positive feedback loop connecting two ABC transporters respectively and are actively involved in TIAs responding to ET and MeJA in C. roseus.}, } @article {pmid29966513, year = {2018}, author = {Ozsoy, MG and Özyer, T and Polat, F and Alhajj, R}, title = {Correction to: Realizing drug repositioning by adapting a recommendation system to handle the process.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {250}, pmid = {29966513}, issn = {1471-2105}, abstract = {Following publication of the original article [1], the authors reported that there was an error in the spelling of the name of one of the authors.}, } @article {pmid29964353, year = {2018}, author = {Whittingham, LA and Dunn, PO and Freeman-Gallant, CR and Taff, CC and Johnson, JA}, title = {Major histocompatibility complex variation and blood parasites in resident and migratory populations of the common yellowthroat.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1544-1557}, doi = {10.1111/jeb.13349}, pmid = {29964353}, issn = {1420-9101}, abstract = {Genes of the major histocompatibility complex (MHC) are a critical part of the adaptive immune response, and the most polymorphic genes in the vertebrate genome, especially in passerine birds. This diversity is thought to be influenced by exposure to pathogens which can vary in relation to numerous factors. Migratory behaviour may be a particularly important trait to consider because migratory birds are exposed to a greater number of different pathogens and parasites at both breeding (i.e. temperate) and overwintering (i.e. tropical and subtropical) areas, as well as at stopover sites during migration. Thus, migrants are predicted to have greater MHC diversity than residents. We compared MHC variation, at both class I and II, and levels of haemosporidian infection between one resident and two migratory populations of the common yellowthroat (Geothlypis trichas). We found that residents were less likely to be infected with haemosporidian parasites and had lower MHC diversity at class I; however, variation at MHC class II was greater in residents than migrants, contrary to our prediction. These patterns were not likely to be caused by differences in population demography as genomewide heterozygosity (based on 9225 single nucleotide polymorphisms) was high in all three populations and not correlated with MHC variation. Our different results for MHC class I and II suggest that studies of immune gene variation in relation to life history need to consider that there could be different selection pressures arising from intracellular (class I) and extracellular (class II) pathogens in different populations.}, } @article {pmid29964350, year = {2018}, author = {Kerr, TJ and Matthee, S and Govender, D and Tromp, G and Engelbrecht, S and Matthee, CA}, title = {Viruses as indicators of contemporary host dispersal and phylogeography: an example of feline immunodeficiency virus (FIVPle) in free-ranging African lion (Panthera leo).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1529-1543}, doi = {10.1111/jeb.13348}, pmid = {29964350}, issn = {1420-9101}, support = {74463//National Research Foundation (NRF)/ ; 89620//NRF Scarce Skills Doctoral Scholarship/ ; 13/34//Poliomyelitis Research Foundation (PRF) Masters Bursary/ ; 14/50//PhD Bursary/ ; 13/08//Division of Medical Virology, Department of Pathology, Faculty of Medicine and Health Science, Stellenbosch University/ ; }, abstract = {Measuring contemporary dispersal in highly mobile terrestrial species is challenging, especially when species are characterized by low levels of population differentiation. Directly transmitted viruses can be used as a surrogate for traditional methods of tracking host movement. Feline immunodeficiency virus (FIV) is a species-specific lentivirus, which has an exceptionally high mutation rate and circulates naturally in wild felids. Using samples derived from 35 lion (Panthera leo) prides, we tested the prediction that FIV in lions (FIVPle) can be used to track the dispersal of individuals between prides. As FIVPle subtypes are geographically structured throughout Africa, we predicted that this marker could be used to detect phylogeographic structure of lions at smaller spatial scales. Phylogenetic analyses of FIVPle pol-RT sequences showed that core pride members (females and subadults) shared evolutionary close viral lineages which differed from neighbouring core prides, whereas sequences from sexually mature males associated with the same pride were always the most divergent. In six instances, natal pride associations of divergent male lions could be inferred, on the assumption that FIVPle infections are acquired during early life stages. Congruence between the genetic pattern of FIV and pride structure suggests that vertical transmission plays an important role in lion FIV dynamics. At a fine spatial scale, significant viral geographic structuring was also detected between lions occurring north of the Olifants River within the Kruger National Park (KNP) and those occupying the southern and central regions. This pattern was further supported by phylogenetic analyses and the confinement of FIVPle subtype E to the northern region of KNP. The study provides new insights into the use of retroviral sequences to predict host dispersal and fine-scale contemporary geographic structure in a social felid species.}, } @article {pmid29964131, year = {2018}, author = {Rouzeau, C and Dagkesamanskaya, A and Langer, K and Bibette, J and Baudry, J and Pompon, D and Anton-Leberre, V}, title = {Adaptive response of yeast cells to triggered toxicity of phosphoribulokinase.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {335-342}, doi = {10.1016/j.resmic.2018.06.002}, pmid = {29964131}, issn = {1769-7123}, mesh = {Adaptation, Physiological/genetics ; Amino Acids, Aromatic/biosynthesis ; Anti-Bacterial Agents/pharmacology ; Doxycycline/pharmacology ; Gene Dosage/*genetics ; Metabolic Engineering ; Phosphotransferases (Alcohol Group Acceptor)/*genetics/*metabolism ; Plasmids/genetics ; Saccharomyces cerevisiae/*genetics/*metabolism ; }, abstract = {Adjustment of plasmid copy number resulting from the balance between positive and negative impacts of borne synthetic genes, plays a critical role in the global efficiency of multistep metabolic engineering. Differential expression of co-expressed engineered genes is frequently observed depending on growth phases, metabolic status and triggered adjustments of plasmid copy numbers, constituting a dynamic process contributing to minimize global engineering burden. A yeast model involving plasmid based expression of phosphoribulokinase (PRKp), a key enzyme for the reconstruction of synthetic Calvin cycle, was designed to gain further insights into such a mechanism. A conditional PRK expression cassette was cloned either onto a low (ARS-CEN based) or a high (2-micron origin based) copy number plasmid using complementation of a trp1 genomic mutation as constant positive selection. Evolution of plasmid copy numbers, PRKp expressions, and cell growth rates were dynamically monitored following gene de-repression through external doxycycline concentration shifts. In the absence of RubisCO encoding gene permitting metabolic recycling, PRKp expression that led to depletion of ribulose phosphate, a critical metabolite for aromatic amino-acids biosynthesis, and accumulation of the dead-end diphosphate product contribute to toxicity. Triggered copy number adjustment was found to be a dynamic process depending both on plasmid types and levels of PRK induction. With the ARS-CEN plasmid, cell growth was abruptly affected only when level PRKp expression exceeded a threshold value. In contrast, a proportional relationship was observed with the 2-micron plasmid consistent with large copy number adjustments. Micro-compartment partitioning of bulk cultures by embedding individual cells into inverse culture medium/oil droplets, revealed the presence of slow and fast growing subpopulations that differ in relative proportions for low and high copy number plasmids.}, } @article {pmid29964027, year = {2018}, author = {Morgani, SM and Saiz, N and Garg, V and Raina, D and Simon, CS and Kang, M and Arias, AM and Nichols, J and Schröter, C and Hadjantonakis, AK}, title = {A Sprouty4 reporter to monitor FGF/ERK signaling activity in ESCs and mice.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {104-126}, doi = {10.1016/j.ydbio.2018.06.017}, pmid = {29964027}, issn = {1095-564X}, support = {R01 HD094868/HD/NICHD NIH HHS/United States ; R01 DK084391/DK/NIDDK NIH HHS/United States ; BB/M023370/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 110151/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Tracking/methods ; Embryo, Mammalian/cytology/*embryology ; Embryonic Development/*physiology ; Extracellular Signal-Regulated MAP Kinases/genetics/metabolism ; Fibroblast Growth Factors/genetics/*metabolism ; MAP Kinase Signaling System/*physiology ; Mice ; Mouse Embryonic Stem Cells/cytology/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; Organogenesis/*physiology ; }, abstract = {The FGF/ERK signaling pathway is highly conserved throughout evolution and plays fundamental roles during embryonic development and in adult organisms. While a plethora of expression data exists for ligands, receptors and pathway regulators, we know little about the spatial organization or dynamics of signaling in individual cells within populations. To this end we developed a transcriptional readout of FGF/ERK activity by targeting a histone H2B-linked Venus fluorophore to the endogenous locus of Spry4, an early pathway target, and generated Spry4H2B-Venus embryonic stem cells (ESCs) and a derivative mouse line. The Spry4H2B-Venus reporter was heterogeneously expressed within ESC cultures and responded to FGF/ERK signaling manipulation. In vivo, the Spry4H2B-Venus reporter recapitulated the expression pattern of Spry4 and localized to sites of known FGF/ERK activity including the inner cell mass of the pre-implantation embryo and the limb buds, somites and isthmus of the post-implantation embryo. Additionally, we observed highly localized reporter expression within adult organs. Genetic and chemical disruption of FGF/ERK signaling, in vivo in pre- and post-implantation embryos, abrogated Venus expression establishing the reporter as an accurate signaling readout. This tool will provide new insights into the dynamics of the FGF/ERK signaling pathway during mammalian development.}, } @article {pmid29964026, year = {2018}, author = {Berenguer, M and Lancman, JJ and Cunningham, TJ and Dong, PDS and Duester, G}, title = {Mouse but not zebrafish requires retinoic acid for control of neuromesodermal progenitors and body axis extension.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {127-131}, pmid = {29964026}, issn = {1095-564X}, support = {P30 CA030199/CA/NCI NIH HHS/United States ; R01 AR067731/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Embryo, Mammalian/cytology/*embryology ; Embryo, Nonmammalian/cytology/*embryology ; Mesoderm/cytology/*embryology ; Mice ; Neural Stem Cells/cytology/*metabolism ; Species Specificity ; Tretinoin/*metabolism ; Zebrafish/*embryology ; }, abstract = {In mouse, retinoic acid (RA) is required for the early phase of body axis extension controlled by a population of neuromesodermal progenitors (NMPs) in the trunk called expanding-NMPs, but not for the later phase of body axis extension controlled by a population of NMPs in the tail called depleting-NMPs. Recent observations suggest that zebrafish utilize depleting-NMPs but not expanding-NMPs for body axis extension. In zebrafish, a role for RA in body axis extension was not supported by previous studies on aldh1a2 (raldh2) mutants lacking RA synthesis. Here, by treating zebrafish embryos with an RA synthesis inhibitor, we also found that body axis extension and somitogenesis was not perturbed, although loss of pectoral fin and cardiac edema were observed consistent with previous studies. The conclusion that zebrafish diverges from mouse in not requiring RA for body axis extension is consistent with zebrafish lacking early expanding-NMPs to generate the trunk. We suggest that RA control of body axis extension was added to higher vertebrates during evolution of expanding-NMPs.}, } @article {pmid29961959, year = {2018}, author = {Franklin, OD and Skúlason, S and Morrissey, MB and Ferguson, MM}, title = {Natural selection for body shape in resource polymorphic Icelandic Arctic charr.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1498-1512}, doi = {10.1111/jeb.13346}, pmid = {29961959}, issn = {1420-9101}, support = {//Natural Sciences and Engineering Research Council of Canada/ ; //Madame Vigdís Finnbogadóttir Scholarship/ ; }, abstract = {Resource polymorphisms exhibit remarkable intraspecific diversity and in many cases are expected to be maintained by diversifying selection. Phenotypic trade-offs can constrain morphologically intermediate individuals from effectively exploiting both alternate resources, resulting in ecological barriers to gene flow. Determining if and how phenotypic trade-offs cause fitness variation in the wild is challenging because of phenotypic and environmental correlations associated with alternative resource strategies. We investigated multiple pathways through which morphology could affect organismal performance, as measured by growth rate, and whether these effects generate diversifying selection in polymorphic Icelandic Arctic charr (Salvelinus alpinus) populations. We considered direct effects of morphology on growth and indirect effects via trophic resource use, estimated by stable isotopic signatures, and via parasitism associated with trophic resources. We sampled over 3 years in (lakes) Thingvallavatn and Vatnshlíðarvatn using the extended selection gradient path analytical approach and estimating size-dependent mortality. We found evidence for diversifying selection only in Thingvallavatn: more streamlined and terminally mouthed planktivore charr experienced greater growth, with the opposite pattern in small benthic charr. However, this effect was mediated by parasitism and nontrophic pathways, rather than trophic performance as often expected. Detection of between-morph differences in the presence (Vatnshlíðarvatn) and direction (Thingvallavatn) of size-dependent mortality, together with nontrophic effects of shape, suggests that a morphological trophic performance explanation for polymorphism is insufficient. This rare insight into selection during early diversification suggests that a complex of interacting local factors must be considered to understand how phenotype influences fitness, despite morphological variation reflecting intuitive trade-off explanations.}, } @article {pmid29961894, year = {2018}, author = {Yang, Z and Shi, H and Ma, P and Zhao, S and Kong, Q and Bian, T and Gong, C and Zhao, Q and Liu, Y and Qi, X and Zhang, X and Han, Y and Liu, J and Li, Q and Chen, H and Su, B}, title = {Darwinian positive selection on the pleiotropic effects of KITLG explain skin pigmentation and winter temperature adaptation in Eurasians.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy136}, pmid = {29961894}, issn = {1537-1719}, abstract = {Human skin color diversity is considered an adaptation to environmental conditions such as UV radiation. Investigations into the genetic bases of such adaptation have identified a group of pigmentation genes contributing to skin color diversity in African and non-African populations. Here we present a population analysis of the pigmentation gene KITLG with previously reported signal of Darwinian positive selection in both European and East Asian populations. We demonstrated that there had been recurrent selective events in the upstream and the downstream regions of KITLG in Eurasian populations. More importantly, besides the expected selection on the KITLG variants favoring light skin in coping with the weak UV radiation at high latitude, we observed a KITLG variant showing adaptation to winter temperature. In particular, compared to UV radiation, winter temperature showed a much stronger correlation with the prevalence of the presumably adaptive KITLG allele in Asian populations. This observation was further supported by the in vitro functional test at low temperature. Consequently, the pleiotropic effects of KITLG, i.e. pigmentation and thermogenesis were both targeted by natural selection that acted on different KITLG sequence variants, contributing to the adaptation of Eurasians to both UV radiation and winter temperature at high latitude areas.}, } @article {pmid29961874, year = {2018}, author = {Behzad, H and Mineta, K and Gojobori, T}, title = {Global Ramifications of Dust and Sandstorm Microbiota.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1970-1987}, pmid = {29961874}, issn = {1759-6653}, mesh = {Agriculture ; *Dust ; Ecosystem ; Geography ; Humans ; *Internationality ; Metagenomics ; *Microbiota ; }, abstract = {Dust and sandstorm events inject substantial quantities of foreign microorganisms into global ecosystems, with the ability to impact distant environments. The majority of these microorganisms originate from deserts and drylands where the soil is laden with highly stress-resistant microbes capable of thriving under extreme environmental conditions, and a substantial portion of them survive long journeys through the atmosphere. This large-scale transmission of highly resilient alien microbial contaminants raises concerns with regards to the invasion of sensitive and/or pristine sink environments, and to human health-concerns exacerbated by increases in the rate of desertification. Further increases in the transport of dust-associated microbiota could extend the spread of foreign microbes to new ecosystems, increase their load in present sink environments, disrupt ecosystem balance, and potentially introduce new pathogens. Our present understanding of these microorganisms, their phylogenic affiliations and functional significance, is insufficient to determine their impact. The purpose of this review is to provide an overview of available data regarding dust and sandstorm microbiota and their potential ramifications on human and ecosystem health. We conclude by discussing current gaps in dust and sandstorm microbiota research, and the need for collaborative studies involving high-resolution meta-omic approaches in conjunction with extensive ecological time-series studies to advance the field towards an improved and sufficient understanding of these invisible atmospheric travelers and their global ramifications.}, } @article {pmid29961854, year = {2018}, author = {Angst, Š and Baldrian, P and Harantová, L and Cajthaml, T and Frouz, J}, title = {Different twig litter (Salix caprea) diameter does affect microbial community activity and composition but not decay rate.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy126}, pmid = {29961854}, issn = {1574-6941}, abstract = {Small twigs represent a substantial input of organic carbon into forest soils, but potential influencing factors on their decomposition have rarely been investigated. Here, we studied potential effects of twig size on decomposition and associated composition and activity of microbial communities during decomposition. Because the surface area for microbial colonization and the volume of accessible substrate increases with decreasing twig size, we hypothesized that twig size affects both microbial community and decomposition rate. Litterbags with twigs (Salix caprea) of two different diameters were placed within the litter layer and consecutively collected over a seven-year period. We determined the mass loss and microbial measures after each sampling event. The observed microbial parameters suggested a faster microbial colonization of thin twigs, where the proportion of bacteria was higher than in thick twigs. The development of the microbial community in thick twigs was more gradual and the proportion of fungi was higher. Despite this differential and successional development of microbial communities (and against our hypothesis), the mass loss among different twig diameters did not differ after our seven-year experiment, indicating that surface-to-volume ratios, though a primary control on microbial succession, may have limited predictive power for twig decomposition rates.}, } @article {pmid29961048, year = {2018}, author = {Abbey-Lee, RN and Uhrig, EJ and Zidar, J and Favati, A and Almberg, J and Dahlbom, J and Winberg, S and Løvlie, H}, title = {The Influence of Rearing on Behavior, Brain Monoamines, and Gene Expression in Three-Spined Sticklebacks.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {4}, pages = {201-213}, doi = {10.1159/000489942}, pmid = {29961048}, issn = {1421-9743}, abstract = {The causes of individual variation in behavior are often not well understood, and potential underlying mechanisms include both intrinsic and extrinsic factors, such as early environmental, physiological, and genetic differences. In an exploratory laboratory study, we raised three-spined sticklebacks (Gasterosteus aculeatus) under 4 different environmental conditions (simulated predator environment, complex environment, variable social environment, and control). We investigated how these manipulations related to behavior, brain physiology, and gene expression later in life, with focus on brain dopamine and serotonin levels, turnover rates, and gene expression. The different rearing environments influenced behavior and gene expression, but did not alter monoamine levels or metabolites. Specifically, compared to control fish, fish exposed to a simulated predator environment tended to be less aggressive, more exploratory, and more neophobic; and fish raised in both complex and variable social environments tended to be less neophobic. Exposure to a simulated predator environment tended to lower expression of dopamine receptor DRD4A, a complex environment increased expression of dopamine receptor DRD1B, while a variable social environment tended to increase serotonin receptor 5-HTR2B and serotonin transporter SLC6A4A expression. Despite both behavior and gene expression varying with early environment, there was no evidence that gene expression mediated the relationship between early environment and behavior. Our results confirm that environmental conditions early in life can affect phenotypic variation. However, the mechanistic pathway of the monoaminergic systems translating early environmental variation into observed behavioral responses was not detected.}, } @article {pmid29960843, year = {2018}, author = {Lanusse, C and Canton, C and Virkel, G and Alvarez, L and Costa-Junior, L and Lifschitz, A}, title = {Strategies to Optimize the Efficacy of Anthelmintic Drugs in Ruminants.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {664-682}, doi = {10.1016/j.pt.2018.05.005}, pmid = {29960843}, issn = {1471-5007}, mesh = {Animal Husbandry/*methods ; Animals ; Anthelmintics/*therapeutic use ; Communicable Disease Control/*methods ; Helminthiasis, Animal/*drug therapy ; Ruminants/*parasitology ; }, abstract = {Anthelmintic resistance in human and animal pathogenic helminths has been spreading in prevalence and severity. Multidrug resistance is a widespread problem in livestock animals. The use of available pharmacology-based information is critical to the design of successful future approaches for parasite control. Relevant scientific work supporting the main strategies to optimize anthelmintic therapy in ruminants under the current drug-resistance scenario is described here. We emphasize the need for further integrated pharmaco-parasitological knowledge to extend the lifespan of both traditional and novel anthelmintic compounds, and to progress in the identification of complementary/alternative measures of parasite control in livestock animals.}, } @article {pmid29960747, year = {2018}, author = {Adams Waldorf, KM and Olson, EM and Nelson, BR and Little, ME and Rajagopal, L}, title = {The Aftermath of Zika: Need for Long-Term Monitoring of Exposed Children.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {729-732}, pmid = {29960747}, issn = {1878-4380}, support = {R01 AI100989/AI/NIAID NIH HHS/United States ; R01 AI133976/AI/NIAID NIH HHS/United States ; R21 OD023838/OD/NIH HHS/United States ; }, abstract = {Pregnancy infections with Zika virus are associated with a spectrum of fetal brain injuries beyond microcephaly. Nonmicrocephalic children exposed to Zika virus in utero or early life should undergo neurodevelopmental testing to identify deficits and allow for early intervention. Additionally, long-term monitoring for higher order neurocognitive deficits should be implemented.}, } @article {pmid29959984, year = {2018}, author = {Uribe, JE and Zardoya, R and Puillandre, N}, title = {Phylogenetic relationships of the conoidean snails (Gastropoda: Caenogastropoda) based on mitochondrial genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {898-906}, doi = {10.1016/j.ympev.2018.06.037}, pmid = {29959984}, issn = {1095-9513}, abstract = {With more than 5,000 species, Conoidea is one of the most diversified superfamilies of Gastropoda. Recently, the family-level classification of these venomous predator snails has undergone substantial changes, on the basis of a phylogenetic tree reconstructed combining partial mitochondrial and nuclear gene sequences, and up to 16 families are now recognized. However, phylogenetic relationships among these families remain largely unresolved. Here, we sequenced 20 complete or nearly complete mitochondrial (mt) genomes, which were combined with mt genomes available in GenBank to construct a dataset that included representatives of 80% of the known families, although for some we had only one species or genus as representative. Most of the sequenced conoidean mt genomes shared a constant genome organization, and observed rearrangements were limited exclusively to tRNA genes in a few lineages. Phylogenetic trees were reconstructed using probabilistic methods. Two main monophyletic groups, termed "Clade A" and "Clade B", were recovered with strong support within a monophyletic Conoidea. Clade A (including families Clavatulidae, Horaiclavidae, Turridae s.s., Terebridae, Drilliidae, Pseudomelatomidae, and Cochlespiridae) was composed of four main lineages, one of which was additionally supported by a rearrangement in the gene order. Clade B (including families Conidae, Borsoniidae, Clathurellidae, Mangeliidae, Raphitomidae, and Mitromorphidae) was composed of five main lineages. The reconstructed phylogeny rejected the monophyly of Clavatulidae, Horaiclavidae, Turridae, Pseudomelatomidae, and Conidae, indicating that several of the currently accepted families may be ill-defined. The reconstructed tree also revealed new phylogenetic positions for genera characterized as tentative (Gemmuloborsonia, Lucerapex, and Leucosyrinx), enigmatic (Marshallena) or challenging to place (Fusiturris), which will potentially impact the classification of the Conoidea.}, } @article {pmid29959877, year = {2018}, author = {Holding, ML and Margres, MJ and Rokyta, DR and Gibbs, HL}, title = {Local prey community composition and genetic distance predict venom divergence among populations of the northern Pacific rattlesnake (Crotalus oreganus).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1513-1528}, doi = {10.1111/jeb.13347}, pmid = {29959877}, issn = {1420-9101}, support = {1638872//NSF/ ; //American Society of Naturalists/ ; //Herpetologists' League/ ; //American Museum of Natural History/ ; //American Society of Mammalogists/ ; //California Bureau of Land Management/ ; //Sigma Xi/ ; //American Society of Ichthyologists and Herpetologists/ ; //Chicago Herpetological Society/ ; //Ohio State University/ ; }, abstract = {Identifying the environmental correlates of divergence in functional traits between populations can provide insights into the evolutionary mechanisms that generate local adaptation. Here, we assess patterns of population differentiation in expressed venom proteins in Northern Pacific rattlesnakes (Crotalus oreganus) from 13 locations across California. We evaluate the relative importance of major biotic (prey species community composition), abiotic (temperature, precipitation and elevation) and genetic factors (genetic distance based on RAD-seq loci) as correlates of population divergence in venom phenotypes. We found that over half of the variation in venom composition is associated with among-population differentiation for genetic and environmental variables and that this variation occurred along axes defining previously observed functional trade-offs between venom proteins that have neurotoxic, myotoxic and hemorrhagic effects. Surprisingly, genetic differentiation among populations was the best predictor of venom divergence, accounting for 46% of overall variation, whereas differences in prey community composition and abiotic factors explained smaller amounts of variation (23% and 19%, respectively). The association between genetic differentiation and venom composition could be due to an isolation-by-distance effect or, more likely, an isolation-by-environment effect where selection against recent migrants is strong, producing a correlation between neutral genetic differentiation and venom differentiation. Our findings suggest that even coarse estimates of prey community composition can be useful in understanding the selection pressures acting on patterns of venom protein expression. Additionally, our results suggest that factors other than adaptation to spatial variation in prey need to be considered when explaining population divergence in venom.}, } @article {pmid29959584, year = {2018}, author = {Frank, A and Froese, T}, title = {The Standard Genetic Code can Evolve from a Two-Letter GC Code Without Information Loss or Costly Reassignments.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {2}, pages = {259-272}, pmid = {29959584}, issn = {1573-0875}, support = {IA104717//Dirección General de Asuntos del Personal Académico, Universidad Nacional Autónoma de México/ ; }, mesh = {Codon/analysis ; *Evolution, Molecular ; Genetic Code/*genetics ; Models, Genetic ; Nucleotides/analysis ; *Origin of Life ; }, abstract = {It is widely agreed that the standard genetic code must have been preceded by a simpler code that encoded fewer amino acids. How this simpler code could have expanded into the standard genetic code is not well understood because most changes to the code are costly. Taking inspiration from the recently synthesized six-letter code, we propose a novel hypothesis: the initial genetic code consisted of only two letters, G and C, and then expanded the number of available codons via the introduction of an additional pair of letters, A and U. Various lines of evidence, including the relative prebiotic abundance of the earliest assigned amino acids, the balance of their hydrophobicity, and the higher GC content in genome coding regions, indicate that the original two nucleotides were indeed G and C. This process of code expansion probably started with the third base, continued with the second base, and ended up as the standard genetic code when the second pair of letters was introduced into the first base. The proposed process is consistent with the available empirical evidence, and it uniquely avoids the problem of costly code changes by positing instead that the code expanded its capacity via the creation of new codons with extra letters.}, } @article {pmid29959476, year = {2018}, author = {Tripathi, S and Deem, MW}, title = {The Standard Genetic Code Facilitates Exploration of the Space of Functional Nucleotide Sequences.}, journal = {Journal of molecular evolution}, volume = {86}, number = {6}, pages = {325-339}, pmid = {29959476}, issn = {1432-1432}, support = {PHY-1427654//National Science Foundation/ ; }, abstract = {The standard genetic code is well known to be optimized for minimizing the phenotypic effects of single-nucleotide substitutions, a property that was likely selected for during the emergence of a universal code. Given the fitness advantage afforded by high standing genetic diversity in a population in a dynamic environment, it is possible that selection to explore a large fraction of the space of functional proteins also occurred. To determine whether selection for such a property played a role during the emergence of the nearly universal standard genetic code, we investigated the number of functional variants of the Escherichia coli PhoQ protein explored at different time scales under translation using different genetic codes. We found that the standard genetic code is highly optimal for exploring a large fraction of the space of functional PhoQ variants at intermediate time scales as compared to random codes. Environmental changes, in response to which genetic diversity in a population provides a fitness advantage, are likely to have occurred at these intermediate time scales. Our results indicate that the ability of the standard code to explore a large fraction of the space of functional sequence variants arises from a balance between robustness and flexibility and is largely independent of the property of the standard code to minimize the phenotypic effects of mutations. We propose that selection to explore a large fraction of the functional sequence space while minimizing the phenotypic effects of mutations contributed toward the emergence of the standard code as the universal genetic code.}, } @article {pmid29959411, year = {2018}, author = {Roukos, V}, title = {Actin proteins assemble to protect the genome.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {35-37}, doi = {10.1038/d41586-018-05339-y}, pmid = {29959411}, issn = {1476-4687}, } @article {pmid29959410, year = {2018}, author = {Guertin, DA}, title = {Unexpected cell population gives fat a brake.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {41-42}, doi = {10.1038/d41586-018-05120-1}, pmid = {29959410}, issn = {1476-4687}, mesh = {*Adipogenesis ; Animals ; *Gastrointestinal Transit ; Stromal Cells ; }, } @article {pmid29959409, year = {2018}, author = {Zilkha, N and Kimchi, T}, title = {A molecular signature for social isolation identified in the brain.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {38-40}, doi = {10.1038/d41586-018-05447-9}, pmid = {29959409}, issn = {1476-4687}, mesh = {*Brain ; Neuropeptides ; Neurosciences ; *Social Isolation ; }, } @article {pmid29959210, year = {2018}, author = {Fan, SM and Chang, YT and Chen, CL and Wang, WH and Pan, MK and Chen, WP and Huang, WY and Xu, Z and Huang, HE and Chen, T and Plikus, MV and Chen, SK and Lin, SJ}, title = {External light activates hair follicle stem cells through eyes via an ipRGC-SCN-sympathetic neural pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6880-E6889}, pmid = {29959210}, issn = {1091-6490}, support = {R01 AR067273/AR/NIAMS NIH HHS/United States ; R01 AR069653/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Hair Follicle/cytology/*metabolism ; *Light ; Mice ; Mice, Transgenic ; Neural Pathways/cytology/*metabolism ; Retinal Ganglion Cells/cytology/*metabolism ; Stem Cells/cytology/*metabolism ; Suprachiasmatic Nucleus/cytology/*metabolism ; }, abstract = {Changes in external light patterns can alter cell activities in peripheral tissues through slow entrainment of the central clock in suprachiasmatic nucleus (SCN). It remains unclear whether cells in otherwise photo-insensitive tissues can achieve rapid responses to changes in external light. Here we show that light stimulation of animals' eyes results in rapid activation of hair follicle stem cells with prominent hair regeneration. Mechanistically, light signals are interpreted by M1-type intrinsically photosensitive retinal ganglion cells (ipRGCs), which signal to the SCN via melanopsin. Subsequently, efferent sympathetic nerves are immediately activated. Increased norepinephrine release in skin promotes hedgehog signaling to activate hair follicle stem cells. Thus, external light can directly regulate tissue stem cells via an ipRGC-SCN autonomic nervous system circuit. Since activation of sympathetic nerves is not limited to skin, this circuit can also facilitate rapid adaptive responses to external light in other homeostatic tissues.}, } @article {pmid29959209, year = {2018}, author = {Urgolites, ZJ and Smith, CN and Squire, LR}, title = {Eye movements support the link between conscious memory and medial temporal lobe function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7599-7604}, pmid = {29959209}, issn = {1091-6490}, support = {I01 CX000359/CX/CSRD VA/United States ; I01 CX001375/CX/CSRD VA/United States ; IK6 CX001644/CX/CSRD VA/United States ; T32 AG000216/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; *Eye Movements ; Female ; Humans ; Male ; *Memory ; Memory Disorders/*physiopathology ; *Pattern Recognition, Visual ; Temporal Lobe/*physiopathology ; }, abstract = {When individuals select the recently studied (and familiar) item in a multiple-choice memory test, they direct a greater proportion of viewing time toward the to-be-selected item when their choice is correct than when their choice is incorrect. Thus, for both correct and incorrect choices, individuals indicate that the chosen item is old, but viewing time nevertheless distinguishes between old and new items. What kind of memory supports this preferential viewing effect? We recorded eye movements while participants made three-alternative, forced-choice recognition memory judgments for scenes. In experiment 1 (n = 30), the magnitude of the preferential viewing effect was strongly correlated with measures of conscious, declarative memory: recognition accuracy as well as the difference in confidence ratings and in response times for correct and incorrect choices. In four analyses that minimized the contribution of declarative memory in order to detect a possible contribution from other processes, the preferential viewing effect was absent. In experiment 2, five memory-impaired patients with medial temporal lobe lesions exhibited a diminished preferential viewing effect. These patients also exhibited poor recognition accuracy and reduced differences in confidence ratings and response times for correct and incorrect choices. We propose that the preferential viewing effect is a phenomenon of conscious, declarative memory and is dependent on the medial temporal lobe. The findings support the link between medial temporal lobe function and declarative memory. When the effects of experience depend on the medial temporal lobe, the effects reflect conscious memory.}, } @article {pmid29959208, year = {2018}, author = {Thomson, R and Yuki, M and Talhelm, T and Schug, J and Kito, M and Ayanian, AH and Becker, JC and Becker, M and Chiu, CY and Choi, HS and Ferreira, CM and Fülöp, M and Gul, P and Houghton-Illera, AM and Joasoo, M and Jong, J and Kavanagh, CM and Khutkyy, D and Manzi, C and Marcinkowska, UM and Milfont, TL and Neto, F and von Oertzen, T and Pliskin, R and San Martin, A and Singh, P and Visserman, ML}, title = {Relational mobility predicts social behaviors in 39 countries and is tied to historical farming and threat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7521-7526}, pmid = {29959208}, issn = {1091-6490}, mesh = {*Agriculture ; Female ; Humans ; Male ; *Social Behavior ; *Social Mobility ; }, abstract = {Biologists and social scientists have long tried to understand why some societies have more fluid and open interpersonal relationships and how those differences influence culture. This study measures relational mobility, a socioecological variable quantifying voluntary (high relational mobility) vs. fixed (low relational mobility) interpersonal relationships. We measure relational mobility in 39 societies and test whether it predicts social behavior. People in societies with higher relational mobility report more proactive interpersonal behaviors (e.g., self-disclosure and social support) and psychological tendencies that help them build and retain relationships (e.g., general trust, intimacy, self-esteem). Finally, we explore ecological factors that could explain relational mobility differences across societies. Relational mobility was lower in societies that practiced settled, interdependent subsistence styles, such as rice farming, and in societies that had stronger ecological and historical threats.}, } @article {pmid29959207, year = {2018}, author = {Kalstrup, T and Blunck, R}, title = {S4-S5 linker movement during activation and inactivation in voltage-gated K+ channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6751-E6759}, pmid = {29959207}, issn = {1091-6490}, support = {MOP-102689//CIHR/Canada ; MOP-136894//CIHR/Canada ; }, mesh = {Animals ; Drosophila Proteins/*chemistry/genetics/metabolism ; Drosophila melanogaster ; Protein Conformation ; Shaker Superfamily of Potassium Channels/*chemistry/genetics/metabolism ; Xenopus laevis ; }, abstract = {The S4-S5 linker physically links voltage sensor and pore domain in voltage-gated ion channels and is essential for electromechanical coupling between both domains. Little dynamic information is available on the movement of the cytosolic S4-S5 linker due to lack of a direct electrical or optical readout. To understand the movements of the gating machinery during activation and inactivation, we incorporated fluorescent unnatural amino acids at four positions along the linker of the Shaker KV channel. Using two-color voltage-clamp fluorometry, we compared S4-S5 linker movements with charge displacement, S4 movement, and pore opening. We found that the proximal S4-S5 linker moves with the S4 helix throughout the gating process, whereas the distal portion undergoes a separate motion related to late gating transitions. Both pore and S4-S5 linker undergo rearrangements during C-type inactivation. In presence of accelerated C-type inactivation, the energetic coupling between movement of the distal S4-S5 linker and pore opening disappears.}, } @article {pmid29959206, year = {2018}, author = {Munsky, B and Li, G and Fox, ZR and Shepherd, DP and Neuert, G}, title = {Distribution shapes govern the discovery of predictive models for gene regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7533-7538}, pmid = {29959206}, issn = {1091-6490}, support = {DP2 GM114849/GM/NIGMS NIH HHS/United States ; R01 GM115892/GM/NIGMS NIH HHS/United States ; R35 GM124747/GM/NIGMS NIH HHS/United States ; }, mesh = {Gene Expression Regulation, Fungal/*physiology ; *Models, Genetic ; RNA, Fungal/*biosynthesis/genetics ; RNA, Messenger/*biosynthesis/genetics ; Saccharomyces cerevisiae/genetics/*metabolism ; }, abstract = {Despite substantial experimental and computational efforts, mechanistic modeling remains more predictive in engineering than in systems biology. The reason for this discrepancy is not fully understood. One might argue that the randomness and complexity of biological systems are the main barriers to predictive understanding, but these issues are not unique to biology. Instead, we hypothesize that the specific shapes of rare single-molecule event distributions produce substantial yet overlooked challenges for biological models. We demonstrate why modern statistical tools to disentangle complexity and stochasticity, which assume normally distributed fluctuations or enormous datasets, do not apply to the discrete, positive, and nonsymmetric distributions that characterize mRNA fluctuations in single cells. As an example, we integrate single-molecule measurements and advanced computational analyses to explore mitogen-activated protein kinase induction of multiple stress response genes. Through systematic analyses of different metrics to compare the same model to the same data, we elucidate why standard modeling approaches yield nonpredictive models for single-cell gene regulation. We further explain how advanced tools recover precise, reproducible, and predictive understanding of transcription regulation mechanisms, including gene activation, polymerase initiation, elongation, mRNA accumulation, spatial transport, and decay.}, } @article {pmid29959205, year = {2018}, author = {Falster, DS and Duursma, RA and FitzJohn, RG}, title = {How functional traits influence plant growth and shade tolerance across the life cycle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6789-E6798}, pmid = {29959205}, issn = {1091-6490}, mesh = {Adaptation, Biological/*physiology ; *Models, Biological ; Plant Development/*physiology ; Plants/*genetics ; *Quantitative Trait, Heritable ; }, abstract = {Plant species differ in many functional traits that drive differences in rates of photosynthesis, biomass allocation, and tissue turnover. However, it remains unclear how-and even if-such traits influence whole-plant growth, with the simple linear relationships predicted by existing theory often lacking empirical support. Here, we present a theoretical framework for understanding the effect of diverse functional traits on plant growth and shade tolerance by extending a widely used model, linking growth rate in seedlings with a single leaf trait, to explicitly include influences of size, light environment, and five prominent traits: seed mass, height at maturation, leaf mass per unit leaf area, leaf nitrogen per unit leaf area, and wood density. Based on biomass growth and allocation, this framework explains why the influence of traits on growth rate and shade tolerance often varies with plant size and why the impact of size on growth varies among traits. Specifically, we demonstrate why for height growth the influence of: (i) leaf mass per unit leaf area is strong in small plants but weakens with size; (ii) leaf nitrogen per unit leaf area does not change with size; (iii) wood density is present across sizes; (iv) height at maturation strengthens with size; and (v) seed mass decreases with size. Moreover, we show how traits moderate plant responses to light environment and also determine shade tolerance, supporting diverse empirical results.}, } @article {pmid29959204, year = {2018}, author = {Geiger-Schuller, K and Sforza, K and Yuhas, M and Parmeggiani, F and Baker, D and Barrick, D}, title = {Extreme stability in de novo-designed repeat arrays is determined by unusually stable short-range interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7539-7544}, pmid = {29959204}, issn = {1091-6490}, support = {R01 GM068462/GM/NIGMS NIH HHS/United States ; T32 GM008403/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Escherichia coli/*chemistry ; Escherichia coli Proteins/*chemistry ; *Helix-Loop-Helix Motifs ; *Models, Molecular ; Sequence Analysis, Protein/*methods ; }, abstract = {Designed helical repeats (DHRs) are modular helix-loop-helix-loop protein structures that are tandemly repeated to form a superhelical array. Structures combining tandem DHRs demonstrate a wide range of molecular geometries, many of which are not observed in nature. Understanding cooperativity of DHR proteins provides insight into the molecular origins of Rosetta-based protein design hyperstability and facilitates comparison of energy distributions in artificial and naturally occurring protein folds. Here, we use a nearest-neighbor Ising model to quantify the intrinsic and interfacial free energies of four different DHRs. We measure the folding free energies of constructs with varying numbers of internal and terminal capping repeats for four different DHR folds, using guanidine-HCl and glycerol as destabilizing and solubilizing cosolvents. One-dimensional Ising analysis of these series reveals that, although interrepeat coupling energies are within the range seen for naturally occurring repeat proteins, the individual repeats of DHR proteins are intrinsically stable. This favorable intrinsic stability, which has not been observed for naturally occurring repeat proteins, adds to stabilizing interfaces, resulting in extraordinarily high stability. Stable repeats also impart a downhill shape to the energy landscape for DHR folding. These intrinsic stability differences suggest that part of the success of Rosetta-based design results from capturing favorable local interactions.}, } @article {pmid29959203, year = {2018}, author = {Laurent, P and Ch'ng, Q and Jospin, M and Chen, C and Lorenzo, R and de Bono, M}, title = {Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6890-E6899}, pmid = {29959203}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; //Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Caenorhabditis elegans/genetics/metabolism ; *Mutation ; *Neuropeptides/genetics/metabolism ; *Secretory Vesicles/genetics/metabolism ; Sensory Receptor Cells/*metabolism ; *Synaptic Vesicles/genetics/metabolism ; }, abstract = {Neuropeptides are ubiquitous modulators of behavior and physiology. They are packaged in specialized secretory organelles called dense core vesicles (DCVs) that are released upon neural stimulation. Unlike synaptic vesicles, which can be recycled and refilled close to release sites, DCVs must be replenished by de novo synthesis in the cell body. Here, we dissect DCV cell biology in vivo in a Caenorhabditis elegans sensory neuron whose tonic activity we can control using a natural stimulus. We express fluorescently tagged neuropeptides in the neuron and define parameters that describe their subcellular distribution. We measure these parameters at high and low neural activity in 187 mutants defective in proteins implicated in membrane traffic, neuroendocrine secretion, and neuronal or synaptic activity. Using unsupervised hierarchical clustering methods, we analyze these data and identify 62 groups of genes with similar mutant phenotypes. We explore the function of a subset of these groups. We recapitulate many previous findings, validating our paradigm. We uncover a large battery of proteins involved in recycling DCV membrane proteins, something hitherto poorly explored. We show that the unfolded protein response promotes DCV production, which may contribute to intertissue communication of stress. We also find evidence that different mechanisms of priming and exocytosis may operate at high and low neural activity. Our work provides a defined framework to study DCV biology at different neural activity levels.}, } @article {pmid29959195, year = {2018}, author = {Hershey, JWB and Sonenberg, N and Mathews, MB}, title = {Principles of Translational Control.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032607}, pmid = {29959195}, issn = {1943-0264}, abstract = {Protein synthesis involves a complex machinery comprising numerous proteins and RNAs joined by noncovalent interactions. Its function is to link long chains of amino acids into proteins with precise sequences as encoded by the genome. Regulation of protein synthesis, called translational control, occurs both at a global level and at specific messenger RNAs (mRNAs). To understand how translation is regulated, knowledge of the molecular structures and kinetic interactions of its components is needed. This review focuses on the targets of translational control and the mechanisms employed.}, } @article {pmid29959194, year = {2018}, author = {Duchaine, TF and Fabian, MR}, title = {Mechanistic Insights into MicroRNA-Mediated Gene Silencing.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032771}, pmid = {29959194}, issn = {1943-0264}, abstract = {MicroRNAs (miRNAs) posttranscriptionally regulate gene expression by repressing protein synthesis and exert a broad influence over development, physiology, adaptation, and disease. Over the past two decades, great strides have been made toward elucidating how miRNAs go about shutting down messenger RNA (mRNA) translation and promoting mRNA decay.}, } @article {pmid29959193, year = {2018}, author = {Robichaud, N and Sonenberg, N and Ruggero, D and Schneider, RJ}, title = {Translational Control in Cancer.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032896}, pmid = {29959193}, issn = {1943-0264}, abstract = {The translation of messenger RNAs (mRNAs) into proteins is a key event in the regulation of gene expression. This is especially true in the cancer setting, as many oncogenes and transforming events are regulated at this level. Cancer-promoting factors that are translationally regulated include cyclins, antiapoptotic factors, proangiogenic factors, regulators of cell metabolism, prometastatic factors, immune modulators, and proteins involved in DNA repair. This review discusses the diverse means by which cancer cells deregulate and reprogram translation, and the resulting oncogenic impacts, providing insights into the complexity of translational control in cancer and its targeting for cancer therapy.}, } @article {pmid29959191, year = {2018}, author = {Proud, CG}, title = {Phosphorylation and Signal Transduction Pathways in Translational Control.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a033050}, pmid = {29959191}, issn = {1943-0264}, abstract = {Protein synthesis, including the translation of specific messenger RNAs (mRNAs), is regulated by extracellular stimuli such as hormones and by the levels of certain nutrients within cells. This control involves several well-understood signaling pathways and protein kinases, which regulate the phosphorylation of proteins that control the translational machinery. These pathways include the mechanistic target of rapamycin complex 1 (mTORC1), its downstream effectors, and the mitogen-activated protein (MAP) kinase (extracellular ligand-regulated kinase [ERK]) signaling pathway. This review describes the regulatory mechanisms that control translation initiation and elongation factors, in particular the effects of phosphorylation on their interactions or activities. It also discusses current knowledge concerning the impact of these control systems on the translation of specific mRNAs or subsets of mRNAs, both in physiological processes and in diseases such as cancer.}, } @article {pmid29959190, year = {2018}, author = {Kwan, T and Thompson, SR}, title = {Noncanonical Translation Initiation in Eukaryotes.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a032672}, pmid = {29959190}, issn = {1943-0264}, abstract = {The vast majority of eukaryotic messenger RNAs (mRNAs) initiate translation through a canonical, cap-dependent mechanism requiring a free 5' end and 5' cap and several initiation factors to form a translationally active ribosome. Stresses such as hypoxia, apoptosis, starvation, and viral infection down-regulate cap-dependent translation during which alternative mechanisms of translation initiation prevail to express proteins required to cope with the stress, or to produce viral proteins. The diversity of noncanonical initiation mechanisms encompasses a broad range of strategies and cellular cofactors. Herein, we provide an overview and, whenever possible, a mechanistic understanding of the various noncanonical mechanisms of initiation used by cells and viruses. Despite many unanswered questions, recent advances have propelled our understanding of the scope, diversity, and mechanisms of alternative initiation.}, } @article {pmid29958983, year = {2018}, author = {Landis, JB and Bell, CD and Hernandez, M and Zenil-Ferguson, R and McCarthy, EW and Soltis, DE and Soltis, PS}, title = {Evolution of floral traits and impact of reproductive mode on diversification in the phlox family (Polemoniaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {878-890}, doi = {10.1016/j.ympev.2018.06.035}, pmid = {29958983}, issn = {1095-9513}, abstract = {Pollinator-mediated selection is a major driver of evolution in flowering plants, contributing to the vast diversity of floral features. Despite long-standing interest in floral variation and the evolution of pollination syndromes in Polemoniaceae, the evolution of floral traits and known pollinators has not been investigated in an explicit phylogenetic context. Here we explore macroevolutionary patterns of both pollinator specificity and three floral traits long considered important determinants of pollinator attraction across the most comprehensive species-level phylogenetic tree yet produced for the family. The presence of floral chlorophyll is reconstructed as the ancestral character state of the family, even though the presence of floral anthocyanins is the most prevalent floral pigment in extant taxa. Mean corolla length and width of the opening of the floral tube are correlated, and both appear to vary with pollinator type. The evolution of pollination systems appears labile, with multiple gains and losses of selfing and conflicting implications for patterns of diversification. Explicit testing of diversification models rejects the hypothesis that selfing is an evolutionary dead-end. This study begins to disentangle the individual components that comprise pollination syndromes and lays the foundation for future work on the genetic mechanisms that control each trait.}, } @article {pmid29958982, year = {2018}, author = {Aziz-Ul-Rahman, and Munir, M and Shabbir, MZ}, title = {Comparative evolutionary and phylogenomic analysis of Avian avulaviruses 1-20.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {931-951}, doi = {10.1016/j.ympev.2018.06.040}, pmid = {29958982}, issn = {1095-9513}, abstract = {Avian avulaviruses (avulaviruses or AAvVs) infect a wide range of avian species worldwide with variable clinical outcomes and economic impacts. Owing to broad host spectrum, several novel avulaviruses are being reported from both wild and domesticated birds that highlight the potential of the virus to evolve, adapt and emerge in susceptible population. Pathobiological and phylogenetic characterizations of individual avulaviruses are often demonstrated, however, a cumulative and comparative assessment of avulaviruses remains elusive. To assess evolutionary dynamics and potential emergence of novel avulaviruses, we enriched existing databases of all known avulaviruses (specie-type 1-20), and determined their genomics features based on both complete genomes and individual complete genes. While a high nucleotide divergence (up to 65.4%) was observed among avulaviruses, phylogenomic analysis revealed clustering of all avulaviruses into three distinct clades. The major clade (Clade-I) included both oldest and newest avulaviruses (2, 5, 6, 7, 8, 10, 11, 14, 15 and 20) and the second clade (Clade-II) consisted of avulaviruses 1, 9, 12, 13, 16, 17, 18 and 19, whereas the third clade (Clade-III) carried only avulaviruses 3 and 4. Intriguingly, clustering pattern was descriptive for individual gene-based analysis, however, the hemagglutinin-neuraminidase (HN) and polymerase (L) genes showed clear and discrete branching patterns similar to complete genome-based clustering. Therefore, we propose the use of HN, or L genes or complete genome to study epidemiological aspects of the avulaviruses. Genomic and residue characteristics of all genes indicated a continuous evolution of the virus, and substitutions in biologically important motifs warrant future investigations to assess their roles in the pathobiology of the virus. Taken together, this comprehensive analysis of all known avulaviruses ascertains continuous monitoring and surveillance of wild/water-fowls and commercial poultry. These findings further our understanding on the evolutionary dynamics and potential emergence of novel avulaviruses and will establish bases to identify potential of wild-bird origin apathogenic viruses to cause infections in commercial poultry.}, } @article {pmid29958981, year = {2018}, author = {Ruiz-Vega, ML and Hernández-Canchola, G and León-Paniagua, L}, title = {Molecular systematics and phylogeography of the endemic Osgood's deermouse Osgoodomys banderanus (Rodentia: Cricetidae) in the lowlands of western Mexico.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {867-877}, doi = {10.1016/j.ympev.2018.06.034}, pmid = {29958981}, issn = {1095-9513}, abstract = {Osgoodomys banderanus is a recognized and endemic rodent species of western Mexico, an area known for its high biodiversity and number of endemisms. Phylogeographical relationships within this taxon were analyzed based on mitochondrial (ND3, tRNA-Arginine, ND4L and partial ND4) and nuclear (GHR) nucleotide sequences. We obtained a total of 112 samples from 22 localities, covering the complete distribution of the species. Phylogenetic analyses using Maximum Likelihood and Bayesian inference confirmed that Osgoodomys is a monophyletic group. In addition, phylogenetic and phylogeographic analyses detected three major clades, which do not coincide with the recognized subspecies of O. banderanus. The genetic lineages detected are the western clade (Nayarit, Jalisco and northern Colima), the central clade (Colima, Michoacán, and northern Guerrero) and the eastern clade (central and southern Guerrero). Genetic distances among clades (5-9%) and nucleotide substitutions (30-88) among haplogroups were high, especially in the southern group. Mountain ranges such as the Transmexican Volcanic Belt and the Sierra Madre del Sur, as well as the Balsas River act as geographical barriers for Osgoodomys. Our results suggest the presence of three independent species, which need to be characterized morphologically to confirm our hypothesis.}, } @article {pmid29958899, year = {2018}, author = {Schiffmacher, AT and Adomako-Ankomah, A and Xie, V and Taneyhill, LA}, title = {Cadherin-6B proteolytic N-terminal fragments promote chick cranial neural crest cell delamination by regulating extracellular matrix degradation.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.06.018}, pmid = {29958899}, issn = {1095-564X}, support = {R01 DE024217/DE/NIDCR NIH HHS/United States ; }, abstract = {During epithelial-to-mesenchymal transitions (EMTs), chick cranial neural crest cells simultaneously delaminate from the basement membrane and segregate from the epithelia, in part, via multiple protease-mediated mechanisms. Proteolytic processing of Cadherin-6B (Cad6B) in premigratory cranial neural crest cells by metalloproteinases not only disassembles cadherin-based junctions but also generates shed Cad6B ectodomains or N-terminal fragments (NTFs) that may possess additional roles. Here we report that Cad6B NTFs promote delamination by enhancing local extracellular proteolytic activity around neural crest cells undergoing EMT en masse. During EMT, Cad6B NTFs of varying molecular weights are observed, indicating that Cad6B may be cleaved at different sites by A Disintegrin and Metalloproteinases (ADAMs) 10 and 19 as well as by other matrix metalloproteinases (MMPs). To investigate Cad6B NTF function, we first generated NTF constructs that express recombinant NTFs with similar relative mobilities to those NTFs shed in vivo. Overexpression of either long or short Cad6B NTFs in premigratory neural crest cells reduces laminin and fibronectin levels within the basement membrane, which then facilitates precocious neural crest cell delamination. Zymography assays performed with supernatants of neural crest cell explants overexpressing Cad6B long NTFs demonstrate increased MMP2 activity versus controls, suggesting that Cad6B NTFs promote delamination through a mechanism involving MMP2. Interestingly, this increase in MMP2 does not involve up-regulation of MMP2 or its regulators at the transcriptional level but instead may be attributed to a physical interaction between shed Cad6B NTFs and MMP2. Taken together, these results highlight a new function for Cad6B NTFs and provide insight into how cadherins regulate cellular delamination during normal developmental EMTs as well as aberrant EMTs that underlie human disease.}, } @article {pmid29958898, year = {2018}, author = {Uchida, A and Yajima, M}, title = {An optogenetic approach to control protein localization during embryogenesis of the sea urchin.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {19-30}, pmid = {29958898}, issn = {1095-564X}, support = {R01 GM126043/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified/*embryology/genetics ; Avena/genetics ; Embryo, Nonmammalian/*embryology ; Embryonic Development/*physiology ; Optogenetics/*methods ; Phototropins/biosynthesis/genetics ; Strongylocentrotus purpuratus/*embryology/genetics ; }, abstract = {Light inducible protein-protein interactions have been used to manipulate protein localization and function in the cell with utmost spatial and temporal precision. In this technical report, we use a recently developed optogenetic approach to manipulate protein localization in the developing sea urchin embryo. A photosensitive LOV domain from Avena sativa phototropin1 cages a small peptide that binds the engineered PDZ domain (ePDZ) upon blue light irradiation. Using this system, mCherry tagged proteins fused with the LOV domain were recruited to ectopic sub-cellular regions such as the membrane, microtubules, or actin by GFP tagged proteins fused with the ePDZ domain upon blue light irradiation within 1-3 min in the sea urchin embryo. The efficiency and speed of recruitment of each protein to its respective subcellular region appeared to be dependent on the power and duration of laser irradiation, as well as the respective level of affinity to the tagged location. Controlled laser irradiation allowed partial recruitment of the spindle to the membrane, and resulted in cell blebbing. Vasa, a cell cycle and germline factor that localizes on the spindle and enriches in the micromeres at 8-16 cell stage was recruited to ectopic sites, preventing normal enrichment. Continuous blue light activation with a regular blue aquarium light over two days of culture successfully induced LOV-ePDZ binding in the developing embryos, resulting in continued ectopic recruitment of Vasa and failure in gastrulation at Day 2. Although some cytotoxicity was observed with prolonged blue light irradiation, this optogenetic system provides a promising approach to test the sub-cellular activities of developmental factors, as well as to alter protein localization and development during embryogenesis.}, } @article {pmid29958813, year = {2018}, author = {Kelly-Hope, LA and Blundell, HJ and Macfarlane, CL and Molyneux, DH}, title = {Innovative Surveillance Strategies to Support the Elimination of Filariasis in Africa.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {694-711}, doi = {10.1016/j.pt.2018.05.004}, pmid = {29958813}, issn = {1471-5007}, mesh = {Africa ; *Disease Eradication ; Elephantiasis, Filarial/*prevention & control ; Humans ; Public Health Surveillance/*methods ; Tropical Medicine ; World Health Organization ; }, abstract = {Lymphatic filariasis (LF) and onchocerciasis are two neglected tropical diseases (NTDs) of public health significance targeted for global elimination. The World Health Organization (WHO) African Region is a priority region, with the highest collective burden of LF and onchocerciasis globally. Coendemic loiasis further complicates elimination due to the risk of adverse events associated with ivermectin treatment. A public health framework focusing on health-related data, systematic collection of data, and analysis and interpretation of data is used to highlight the range of innovative surveillance strategies required for filariasis elimination. The most recent and significant developments include: rapid point-of-care test (POCT) diagnostics; clinical assessment tools; new WHO guidelines; open-access online data portals; mHealth platforms; large-scale prevalence maps; and the optimisation of mathematical models.}, } @article {pmid29958536, year = {2018}, author = {MacKay, K and Kusalik, A and Eskiw, CH}, title = {GrapHi-C: graph-based visualization of Hi-C datasets.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {418}, pmid = {29958536}, issn = {1756-0500}, support = {RGPIN 37207//Natural Sciences and Engineering Research Council of Canada/ ; Vanier Canada Graduate Scholarship//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Chromosome Positioning ; Chromosomes ; DNA/genetics ; *Data Visualization ; *Datasets as Topic ; Genome ; *Genomics ; Nucleic Acid Conformation ; }, abstract = {OBJECTIVES: Hi-C is a proximity-based ligation reaction used to detect regions of the genome that are close in 3D space (or "interacting"). Typically, results from Hi-C experiments (contact maps) are visualized as heatmaps or Circos plots. While informative, these visualizations do not directly represent genomic structure and folding, making the interpretation of the underlying 3D genomic organization obscured. Our objective was to generate a graph-based contact map representation that leads to a more intuitive structural visualization.

RESULTS: Normalized contact maps were converted into undirected graphs where each vertex represented a genomic region and each edge represented a detected (intra- and inter-chromosomal) or known (linear) interaction between two regions. Each edge was weighted by the inverse of the linear distance (Hi-C experimental resolution) or the interaction frequency from the contact map. Graphs were generated based on this representation scheme for contact maps from existing fission yeast datasets. Originally, these datasets were used to (1) identify specific principles influencing fission yeast genome organization and (2) uncover changes in fission yeast genome organization during the cell cycle. When compared to the equivalent heatmaps and/or Circos plots, the graph-based visualizations more intuitively depicted the changes in genome organization described in the original studies.}, } @article {pmid29958066, year = {2019}, author = {Eirin-Lopez, JM and Putnam, HM}, title = {Marine Environmental Epigenetics.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {335-368}, doi = {10.1146/annurev-marine-010318-095114}, pmid = {29958066}, issn = {1941-0611}, abstract = {Marine organisms' persistence hinges on the capacity for acclimatization and adaptation to the myriad of interacting environmental stressors associated with global climate change. In this context, epigenetics-mechanisms that facilitate phenotypic variation through genotype-environment interactions-are of great interest ecologically and evolutionarily. Our comprehensive review of marine environmental epigenetics guides our recommendations of four key areas for future research: the dynamics of wash-in and wash-out of epigenetic effects, the mechanistic understanding of the interplay of different epigenetic marks and the interaction with the microbiome, the capacity for and mechanisms of transgenerational epigenetic inheritance, and the evolutionary implications of the interaction of genetic and epigenetic features. Emerging insights in marine environmental epigenetics can be applied to critical issues such as aquaculture, biomonitoring, and biological invasions, thereby improving our ability to explain and predict the responses of marine taxa to global climate change.}, } @article {pmid29957887, year = {2018}, author = {Schrago, CG and Aguiar, BO and Mello, B}, title = {Comparative evaluation of maximum parsimony and Bayesian phylogenetic reconstruction using empirical morphological data.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1477-1484}, doi = {10.1111/jeb.13344}, pmid = {29957887}, issn = {1420-9101}, support = {310974/2015-1//Brazilian Research Council (CNPq)/ ; 440954/2016-9//Brazilian Research Council (CNPq)/ ; }, abstract = {The use of discrete morphological data in Bayesian phylogenetics has increased significantly over the last years with the proposal of total evidence analysis and the treatment of fossils as terminal taxa in Bayesian molecular dating. Both approaches rely on the assumption that probabilistic Markov models reasonably accommodate all the complexity of morphological evolution of discrete traits. The performance of such morphological models used in Bayesian phylogenetics has been thoroughly investigated, but conclusions so far were based mostly on simulated data. In this study, we have surveyed MorphoBank and obtained a large number of morphological matrices to evaluate Bayesian phylogenetic inference (BI) under Lewis' Mk model in comparison with the maximum parsimony (MP) algorithm. We found that trees estimated by both methods frequently differed and that BI generated a larger amount of polytomic tree topologies. The number of trees contained in the 95% Bayesian credibility interval was significantly greater than the number of equally parsimonious trees. We also investigated which factors mostly influenced the topological difference between maximum parsimony and Bayesian tree topologies and found that the number of terminals in morphological matrices was the variable with the highest association with the topological distance between trees inferred by BI and MP. Surprisingly, we show that differences between both approaches were not influenced by increasing sample size. Our results, which were based on a large set of empirical matrices, corroborate recent findings that BI is less precise than MP.}, } @article {pmid29957883, year = {2018}, author = {Kangassalo, K and Valtonen, TM and Sorvari, J and Kecko, S and Pölkki, M and Krams, I and Krama, T and Rantala, MJ}, title = {Independent and interactive effects of immune activation and larval diet on adult immune function, growth and development in the greater wax moth (Galleria mellonella).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1485-1497}, doi = {10.1111/jeb.13345}, pmid = {29957883}, issn = {1420-9101}, support = {//Jenny and Antti Wihuri Foundation/ ; //Turku University Foundation/ ; //Academy of Finland/ ; }, abstract = {Organisms in the wild are likely to face multiple immune challenges as well as additional ecological stressors, yet their interactive effects on immune function are poorly understood. Insects are found to respond to cues of increased infection risk by enhancing their immune capacity. However, such adaptive plasticity in immune function may be limited by physiological and environmental constraints. Here, we investigated the effects of two environmental stressors - poor larval diet and an artificial parasite-like immune challenge at the pupal stage - on adult immune function, growth and development in the greater wax moth (Galleria mellonella). Males whose immune system was activated with an artificial parasite-like immune challenge had weaker immune response - measured as strength of encapsulation response - as adults compared to the control groups, but only when reared on high-nutrition larval diet. Immune activation did not negatively affect adult immune response in males reared on low-nutrition larval diet, indicating that poor larval diet improved the capacity of the insects to respond to repeated immune challenges. Low-nutrition larval diet also had a positive independent effect on immune capacity in females, yet it negatively affected development time and adult body mass in both sexes. As in the nature immune challenges are rarely isolated, and adverse nutritional environment may indicate an elevated risk of infection, resilience to repeated immune challenges as a response to poor nutritional conditions could provide a significant fitness advantage. This study highlights the importance of considering environmental context when investigating the effects of immune activation in insects.}, } @article {pmid29957856, year = {2018}, author = {Santos, BF and Perrard, A}, title = {Testing the Dutilleul syndrome: host use drives the convergent evolution of multiple traits in parasitic wasps.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1430-1439}, doi = {10.1111/jeb.13343}, pmid = {29957856}, issn = {1420-9101}, support = {//American Museum of Natural History/ ; mini-ARTS grant//Society of Systematic Biologists/ ; //University of California Berkeley/ ; 1501802//National Science Foundation/ ; //Annette Kade Graduate Student Fellowship/ ; //Theodore Roosevelt Memorial Grant/ ; //Jessup Award/ ; //Academy of Natural Sciences of Drexel University/ ; //Essig Museum Visiting Taxonomist Award/ ; }, abstract = {Common life-history aspects among independent lineages often result in the repeated evolution of suites of adaptive traits, or 'syndromes'. Such syndromes can be key avenues to understand relationships between morphological and ecological traits, but are rarely tested due to insufficient trait shift repetitions. We use a hyperdiverse lineage to investigate the evolution of a syndrome. Cryptine ichneumonid wasps that parasitize insects concealed in hard substrates display several traits that are putative adaptations to that end. Using a phylogenetic framework from a combined multigene molecular and morphological data set with 308 cryptine species, we tested whether these traits were part of a morphofunctional syndrome related to host use. Ancestral state estimations show multiple origins for six investigated traits, which are correlated to each other and to the use of deeply concealed hosts, suggesting adaptation. Putatively adaptive traits showed a much stronger link among themselves than with an assemblage of 49 other morphological traits. However, estimation of the order of evolution in adaptive traits showed no structured pattern. The results indicate that the challenge of attacking deeply concealed hosts induced the repeated evolution of a 'Dutilleul syndrome', named after the 'walker-through-walls' character from French literature. They also point towards a dynamic scenario in the evolution of complex functional systems. These findings highlight the power of morphology to illuminate poorly known aspects of natural history, and how hyperdiverse lineages can be used to understand the evolution of complex traits.}, } @article {pmid29957174, year = {2018}, author = {Ramaprasad, EVV and Mahidhara, G and Sasikala, C and Ramana, CV}, title = {Rhodococcus electrodiphilus sp. nov., a marine electro active actinobacterium isolated from coral reef.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2644-2649}, doi = {10.1099/ijsem.0.002895}, pmid = {29957174}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; *Coral Reefs ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; India ; Mycolic Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodococcus/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An electrogenic bacterium was isolated from a marine coral, designated as strain JC435T and its taxonomic status examined by using a polyphasic approach. Results from the 16S rRNA gene sequence study showed that the isolate belonged to the genus Rhodococcus and formed a cluster with Rhodococcus ruber KCTC 9806T (99.5 % 16S rRNA gene sequence similarity) and Rhodococcus aetherivorans JCM 14343T (99.3 %), respectively. Genome relatedness based on DNA-DNA hybridization to the type strains of closest-related species was less than 30 % and the ΔTm of >7 °C, suggesting that strain represents a new species of the genus Rhodococcus. The major fatty acids were C16 : 0, C18 : 1ω9c, C18 : 010-methyl and C16 : 1ω6c and/or C16 : 1ω7c. The polar lipids of strain JC435T were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol mannoside, phosphatidylinositol, three unknown phospholipids and an unknown amino lipid. The major isoprenoid quinone was MK-8(H2), with 8 % of MK-7(H2) and 2 % of MK-9(H2) as minor components. Whole-cell hydrolysates contained meso-diaminopimelic acid, arabinose and galactose as the diagnostic diamino acid and sugars. Mycolic acids were detected. The genomic DNA G+C content of strain JC435T was 69.8 mol%. On the basis of phylogenetic genotypic, physiological and chemotaxonomic analysis, strain JC435T is considered to represent a novel species of the genus Rhodococcus for which the name Rhodococcuselectrodiphilus sp. nov. is proposed. The type strain is JC435T (=KCTC 39856T=LMG 29881T=MCC 3659T).}, } @article {pmid29957173, year = {2018}, author = {Chen, DZ and Yu, NN and Chu, QY and Chen, J and Ye, JX and Cheng, ZW and Zhang, SH and Chen, JM}, title = {Piscinibacter caeni sp. nov., isolated from activated sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2627-2632}, doi = {10.1099/ijsem.0.002891}, pmid = {29957173}, issn = {1466-5034}, mesh = {Bacteria/genetics ; Bacterial Typing Techniques ; Base Composition ; Burkholderiales/*classification/genetics/isolation & purification ; Cadaverine/chemistry ; China ; DNA, Bacterial/genetics ; Drug Industry ; Fatty Acids/chemistry ; Industrial Waste ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Putrescine/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Ubiquinone/chemistry ; }, abstract = {A yellowish-pigmented bacterial strain, designated as MQ-18T, was isolated from a sample of activated sludge collected from a pharmaceutical factory in Zhejiang, China. The strain was characterized through a polyphasic taxonomy approach. 16S rRNA gene sequence analysis demonstrated that strain MQ-18T showed high similarities to Piscinibacter defluvii SH-1T (99.7 %) and Piscinibacter aquaticus IMCC1728T (98.4 %), thereby suggesting that it belongs to the genus Piscinibacter. The DNA-DNA relatedness values of this strain to strains SH-1T and IMCC1728T were only 35.4 and 33.3 %, respectively. Cells of MQ-18T were Gram-negative, aerobic, motile, rod-shaped and non-spore forming. This strain exhibited growth at 25-37 °C (optimum: 30 °C) in the presence of 0-3.0 % (w/v) NaCl (optimum, 0 % NaCl) and at pH 5.0-8.0 (pH 7.0). The predominant fatty acids were C12 : 0 (5.5 %), C16 : 0 (33.7 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c; 38.5 %), and summed feature 4 (anteiso-C17 : 1 B and/or iso C17 : 1 I; 11.6 %). The main quinone type was ubiquinone-8, and the major polyamines were cadaverine and putrescine. The major polar lipid profile consisted of diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content was 70.1 mol%. On the basis of its phylogenetic, phenotypic and physiological characteristics, strain MQ-18T is considered to represent a novel species of the genus Piscinibacter, for which the name Piscinibacter caeni sp. nov. is proposed. The type strain is MQ-18T (CCTCC AB 2017223T=JCM 32138T).}, } @article {pmid29957171, year = {2018}, author = {Xia, F and Ou-Yang, TN and Gao, ZH and Qiu, LH}, title = {Edaphobacter flagellatus sp. nov. and Edaphobacter bradus sp. nov., two acidobacteria isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2530-2537}, doi = {10.1099/ijsem.0.002871}, pmid = {29957171}, issn = {1466-5034}, mesh = {Acidobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {Two aerobic and obligately acidophilic bacteria, designated HZ411T and 4MSH08T, were isolated from the forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China (23° 10' N, 112° 31' E). These two strains were Gram-stain-negative short rods that multiplied by binary division. HZ411T was motile, with a single polar flagellum, but 4MSH08T was non-motile. The results of the 16S rRNA gene sequence analysis indicated that these two strains formed a common clade with members of the genusEdaphobacterin subdivision 1 of the phylum Acidobacteria but they each occupied a unique position in the genus. HZ411T and 4MSH08T had a 16S rRNA gene sequence similarity of 96.2 % between each other and the highest sequence similarity of 97.7 and 96.9 % to Edaphobacter modestusJbg-1T and Edaphobacter aggregansWbg-1T, respectively. The DNA-DNA hybridization rate between HZ411T and E. modestusJbg-1T was 22.7 %. The DNA G+C contents of HZ411T and 4MSH08T were 57.7 and 59.3 %, respectively. HZ411T and 4MSH08T had similar major (>10 %) fatty acids with very high percentages of iso-C15 : 0 and C16 : 1ω7c, and similar major polar lipid profiles (both contained a phosphatidylethanolamine, phosphatidyldimethylethanolamine and glycolipid and several unidentified aminolipids and polar lipids). On the basis of these physiological, phylogenetic and chemotaxonomic data, we suggest that HZ411T and 4MSH08T represent two novel species of the genus Edaphobacter, for which the names Edaphobacter flagellatus HZ411T (=GDMCC 1.1193=LMG 30085) and Edaphobacter bradus 4MSH08T (=GDMCC 1.1317=KCTC 62475) are proposed.}, } @article {pmid29957169, year = {2018}, author = {De Meyer, SE and Cnockaert, M and Moulin, L and Howieson, JG and Vandamme, P}, title = {Symbiotic and non-symbiotic Paraburkholderia isolated from South African Lebeckia ambigua root nodules and the description of Paraburkholderia fynbosensis sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2607-2614}, doi = {10.1099/ijsem.0.002884}, pmid = {29957169}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Burkholderiaceae/*classification/isolation & purification ; DNA, Bacterial/genetics ; Fabaceae/*microbiology ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; Quinones/chemistry ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/*microbiology ; Sequence Analysis, DNA ; South Africa ; Symbiosis ; }, abstract = {Nine Gram-negative, rod-shaped bacteria were isolated from Lebeckia ambigua root nodules. All strains were able to nodulate and fix nitrogen with Lebeckia ambigua apart from WSM4178T, WSM4181 and WSM4182. Based on the 16S rRNA gene phylogeny, all strains were closely related to Paraburkholderia species (98.4-99.9 %), belonging to the Betaproteobacteria class and Burkholderiaceae family. According to 16S rRNA gene phylogeny the closest relative for WSM4174-WSM4177 and WSM4179-WSM4180 was Paraburkholderia tuberum(99.80-99.86 %), for WSM4178T was Paraburkholderia caledonica (98.42 %) and for WSM4181-WSM4182 was Paraburkholderia graminis (99.79 %). Analysis of the gyrB and recA housekeeping genes supported the assignment of WSM4181-WSM4182 to P. graminis and the other investigated strains could be assigned to the genus Paraburkholderia. The results of DNA-DNA hybridization, physiological and biochemical tests allowed genotypic and phenotypic differentiation of WSM4178T from the closest validly published Paraburkholderia species. However, WSM4174-WSM4177 and WSM4179-WSM4180 could not reliably be distinguished from its closest neighbour and therefore complete genome comparison was performed between WSM4176 and P. tuberum STM678T which gave ANI values of 96-97 %. Chemotaxonomic data, including fatty acid profiles and quinone data supported the assignment of the strains to the genus Paraburkholderia. On the basis of genotypic and phenotypic data one novel species, Paraburkholderiafynbosensis sp. nov. (WSM4178T=LMG 27177T=HAMBI 3356T), is proposed and the isolation of P. tuberum and P. graminis from root nodules of Lebeckia ambigua is reported.}, } @article {pmid29957168, year = {2018}, author = {Hwang, YJ and Son, JS and Ghim, SY}, title = {Paenibacillus elymi sp. nov., isolated from the rhizosphere of Elymus tsukushiensis, a plant native to the Dokdo Islands, Republic of Korea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2615-2621}, doi = {10.1099/ijsem.0.002892}, pmid = {29957168}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Elymus/*microbiology ; Fatty Acids/chemistry ; Islands ; Paenibacillus/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {Strain KUDC6143T was isolated from the rhizosphere of Elymus tsukushiensis, a plant native to the Dokdo Islands, Republic of Korea. Cells of this bacterial strain were Gram-positive, endospore-forming, motile and rod-shaped. The strain was capable of growth at a temperature of 25-45 °C and at a pH of 6.0-12.0; it showed an optimal growth at a temperature of 30 °C and at a pH of 7.0. In addition, it grew on a tryptic soy agar and in a tryptic soy broth containing less than 4.0 % NaCl (w/v). The cell length ranged from 2.0 to 2.7 µm. KUDC6143T was catalase-negative and oxidase-positive, and it hydrolysed starch but not casein. Its genomic G+C content was 50.3 mol%. Its major fatty acids were anteiso-C15 : 0, C16 : 0, and iso-C16 : 0. Phylogenetic analysis, based on the 16S rRNA gene sequences, showed that KUDC6143T belonged to the genus Paenibacillus, with the most closely related type strain being Paenibacillus pinihumi S23T (97.8 %). Based on its phenotypic characteristics, phylogenetic data and genetic data, strain KUDC6143T should be considered as representing a novel species of the genus Paenibacillus, for which we propose the name Paenibacillus elymi sp. nov. The type strain is KUDC6143T (=KCTC 33853T=DSM 106581T).}, } @article {pmid29955898, year = {2018}, author = {Zheng, Y and Graur, D and Azevedo, RBR}, title = {Correlated Selection on Amino Acid Deletion and Replacement in Mammalian Protein Sequences.}, journal = {Journal of molecular evolution}, volume = {86}, number = {6}, pages = {365-378}, pmid = {29955898}, issn = {1432-1432}, abstract = {A low ratio of nonsynonymous and synonymous substitution rates (dN/dS) at a codon is an indicator of functional constraint caused by purifying selection. Intuitively, the functional constraint would also be expected to prevent such a codon from being deleted. However, to the best of our knowledge, the correlation between the rates of deletion and substitution has never actually been estimated. Here, we use 8595 protein-coding region sequences from nine mammalian species to examine the relationship between deletion rate and dN/dS. We find significant positive correlations at the levels of both sites and genes. We compared our data against controls consisting of simulated coding sequences evolving along identical phylogenetic trees, where deletions occur independently of substitutions. A much weaker correlation was found in the corresponding simulated sequences, probably caused by alignment errors. In the real data, the correlations cannot be explained by alignment errors. Separate investigations on nonsynonymous (dN) and synonymous (dS) substitution rates indicate that the correlation is most likely due to a similarity in patterns of selection rather than in mutation rates.}, } @article {pmid29955873, year = {2018}, author = {Rotem, A and Serohijos, AWR and Chang, CB and Wolfe, JT and Fischer, AE and Mehoke, TS and Zhang, H and Tao, Y and Lloyd Ung, W and Choi, JM and Rodrigues, JV and Kolawole, AO and Koehler, SA and Wu, S and Thielen, PM and Cui, N and Demirev, PA and Giacobbi, NS and Julian, TR and Schwab, K and Lin, JS and Smith, TJ and Pipas, JM and Wobus, CE and Feldman, AB and Weitz, DA and Shakhnovich, EI}, title = {Evolution on the Biophysical Fitness Landscape of an RNA Virus.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2390-2400}, pmid = {29955873}, issn = {1537-1719}, support = {R01 GM068670/GM/NIGMS NIH HHS/United States ; }, abstract = {Viral evolutionary pathways are determined by the fitness landscape, which maps viral genotype to fitness. However, a quantitative description of the landscape and the evolutionary forces on it remain elusive. Here, we apply a biophysical fitness model based on capsid folding stability and antibody binding affinity to predict the evolutionary pathway of norovirus escaping a neutralizing antibody. The model is validated by experimental evolution in bulk culture and in a drop-based microfluidics that propagates millions of independent small viral subpopulations. We demonstrate that along the axis of binding affinity, selection for escape variants and drift due to random mutations have the same direction, an atypical case in evolution. However, along folding stability, selection and drift are opposing forces whose balance is tuned by viral population size. Our results demonstrate that predictable epistatic tradeoffs between molecular traits of viral proteins shape viral evolution.}, } @article {pmid29955862, year = {2018}, author = {Jones, LM and Eves-van den Akker, S and van-Oosten Hawle, P and Atkinson, HJ and Urwin, PE}, title = {Duplication of hsp-110 Is Implicated in Differential Success of Globodera Species under Climate Change.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2401-2413}, pmid = {29955862}, issn = {1537-1719}, support = {P40 OD010440/OD/NIH HHS/United States ; }, abstract = {Managing the emergence and spread of crop pests and pathogens is essential for global food security. Understanding how organisms have adapted to their native climate is key to predicting the impact of climate change. The potato cyst nematodes Globodera pallida and G. rostochiensis are economically important plant pathogens that cause yield losses of up to 50% in potato. The two species have different thermal optima that may relate to differences in the altitude of their regions of origin in the Andes. Here, we demonstrate that juveniles of G. pallida are less able to recover from heat stress than those of G. rostochiensis. Genome-wide analysis revealed that while both Globodera species respond to heat stress by induction of various protective heat-inducible genes, G. pallida experiences heat stress at lower temperatures. We use C. elegans as a model to demonstrate the dependence of the heat stress response on expression of Heat Shock Factor-1 (HSF-1). Moreover, we show that hsp-110 is induced by heat stress in G. rostochiensis, but not in the less thermotolerant G. pallida. Sequence analysis revealed that this gene and its promoter was duplicated in G. rostochiensis and acquired thermoregulatory properties. We show that hsp-110 is required for recovery from acute thermal stress in both C. elegans and in G. rostochiensis. Our findings point towards an underlying molecular mechanism that allows the differential expansion of one species relative to another closely related species under current climate change scenarios. Similar mechanisms may be true of other invertebrate species with pest status.}, } @article {pmid29955180, year = {2018}, author = {Gamazon, ER and Segrè, AV and van de Bunt, M and Wen, X and Xi, HS and Hormozdiari, F and Ongen, H and Konkashbaev, A and Derks, EM and Aguet, F and Quan, J and , and Nicolae, DL and Eskin, E and Kellis, M and Getz, G and McCarthy, MI and Dermitzakis, ET and Cox, NJ and Ardlie, KG}, title = {Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {956-967}, pmid = {29955180}, issn = {1546-1718}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; 203141//Wellcome Trust/United Kingdom ; U01 HG007610/HG/NHGRI NIH HHS/United States ; R01 MH101782/MH/NIMH NIH HHS/United States ; R01 AR042742/AR/NIAMS NIH HHS/United States ; U19 HL065962/HL/NHLBI NIH HHS/United States ; S10 RR025141/RR/NCRR NIH HHS/United States ; 106130//Wellcome Trust/United Kingdom ; R01 CA157823/CA/NCI NIH HHS/United States ; U01 DK105535/DK/NIDDK NIH HHS/United States ; R01 HD074711/HD/NICHD NIH HHS/United States ; 090532//Wellcome Trust/United Kingdom ; RC2 GM092618/GM/NIGMS NIH HHS/United States ; P50 GM115305/GM/NIGMS NIH HHS/United States ; U01 HG006378/HG/NHGRI NIH HHS/United States ; R01 ES022282/ES/NIEHS NIH HHS/United States ; R01 MH101820/MH/NIMH NIH HHS/United States ; UL1 RR024975/RR/NCRR NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R01 NS032830/NS/NINDS NIH HHS/United States ; U01 HG004798/HG/NHGRI NIH HHS/United States ; R01 HG007022/HG/NHGRI NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; 098381//Wellcome Trust/United Kingdom ; R01 MH090937/MH/NIMH NIH HHS/United States ; R01 MH113362/MH/NIMH NIH HHS/United States ; HHSN268201000029C/HL/NHLBI NIH HHS/United States ; R01 MH101814/MH/NIMH NIH HHS/United States ; }, abstract = {We apply integrative approaches to expression quantitative loci (eQTLs) from 44 tissues from the Genotype-Tissue Expression project and genome-wide association study data. About 60% of known trait-associated loci are in linkage disequilibrium with a cis-eQTL, over half of which were not found in previous large-scale whole blood studies. Applying polygenic analyses to metabolic, cardiovascular, anthropometric, autoimmune, and neurodegenerative traits, we find that eQTLs are significantly enriched for trait associations in relevant pathogenic tissues and explain a substantial proportion of the heritability (40-80%). For most traits, tissue-shared eQTLs underlie a greater proportion of trait associations, although tissue-specific eQTLs have a greater contribution to some traits, such as blood pressure. By integrating information from biological pathways with eQTL target genes and applying a gene-based approach, we validate previously implicated causal genes and pathways, and propose new variant and gene associations for several complex traits, which we replicate in the UK BioBank and BioVU.}, } @article {pmid29955179, year = {2018}, author = {Braasch, I and Bobe, J and Guiguen, Y and Postlethwait, JH}, title = {Reply to: 'Subfunctionalization versus neofunctionalization after whole-genome duplication'.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {910-911}, doi = {10.1038/s41588-018-0163-3}, pmid = {29955179}, issn = {1546-1718}, } @article {pmid29955178, year = {2018}, author = {Viswanathan, SR and Nogueira, MF and Buss, CG and Krill-Burger, JM and Wawer, MJ and Malolepsza, E and Berger, AC and Choi, PS and Shih, J and Taylor, AM and Tanenbaum, B and Pedamallu, CS and Cherniack, AD and Tamayo, P and Strathdee, CA and Lage, K and Carr, SA and Schenone, M and Bhatia, SN and Vazquez, F and Tsherniak, A and Hahn, WC and Meyerson, M}, title = {Genome-scale analysis identifies paralog lethality as a vulnerability of chromosome 1p loss in cancer.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {937-943}, pmid = {29955178}, issn = {1546-1718}, support = {U24 CA194107/CA/NCI NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; T32 CA009172/CA/NCI NIH HHS/United States ; P30 ES002109/ES/NIEHS NIH HHS/United States ; U01 CA176058/CA/NCI NIH HHS/United States ; R35 CA197568/CA/NCI NIH HHS/United States ; R01 HG009285/HG/NHGRI NIH HHS/United States ; K99 CA208028/CA/NCI NIH HHS/United States ; U01 CA217885/CA/NCI NIH HHS/United States ; }, abstract = {Functional redundancy shared by paralog genes may afford protection against genetic perturbations, but it can also result in genetic vulnerabilities due to mutual interdependency1-5. Here, we surveyed genome-scale short hairpin RNA and CRISPR screening data on hundreds of cancer cell lines and identified MAGOH and MAGOHB, core members of the splicing-dependent exon junction complex, as top-ranked paralog dependencies6-8. MAGOHB is the top gene dependency in cells with hemizygous MAGOH deletion, a pervasive genetic event that frequently occurs due to chromosome 1p loss. Inhibition of MAGOHB in a MAGOH-deleted context compromises viability by globally perturbing alternative splicing and RNA surveillance. Dependency on IPO13, an importin-β receptor that mediates nuclear import of the MAGOH/B-Y14 heterodimer9, is highly correlated with dependency on both MAGOH and MAGOHB. Both MAGOHB and IPO13 represent dependencies in murine xenografts with hemizygous MAGOH deletion. Our results identify MAGOH and MAGOHB as reciprocal paralog dependencies across cancer types and suggest a rationale for targeting the MAGOHB-IPO13 axis in cancers with chromosome 1p deletion.}, } @article {pmid29955177, year = {2018}, author = {}, title = {Heritable influences on the mind and brain.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {905}, doi = {10.1038/s41588-018-0172-2}, pmid = {29955177}, issn = {1546-1718}, } @article {pmid29955176, year = {2018}, author = {Sandve, SR and Rohlfs, RV and Hvidsten, TR}, title = {Subfunctionalization versus neofunctionalization after whole-genome duplication.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {908-909}, doi = {10.1038/s41588-018-0162-4}, pmid = {29955176}, issn = {1546-1718}, } @article {pmid29955153, year = {2018}, author = {Tumino, A and Spitaleri, C and La Cognata, M and Cherubini, S and Guardo, GL and Gulino, M and Hayakawa, S and Indelicato, I and Lamia, L and Petrascu, H and Pizzone, RG and Puglia, SMR and Rapisarda, GG and Romano, S and Sergi, ML and Spartá, R and Trache, L}, title = {Publisher Correction: An increase in the 12C + 12C fusion rate from resonances at astrophysical energies.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {E3}, doi = {10.1038/s41586-018-0269-x}, pmid = {29955153}, issn = {1476-4687}, abstract = {In equation (1) of this Letter, the closing bracket was missing; in Extended Data Fig. 1 and the accompanying legend, 'Φ(pd)' should have been 'Φ2(pd)', and in the Methods the text "Odd J assignments are uncertain by ±1." has been added. These errors have all been corrected online.}, } @article {pmid29955152, year = {2018}, author = {González-Forero, M and Gardner, A}, title = {Publisher Correction: Inference of ecological and social drivers of human brain-size evolution.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {E32}, doi = {10.1038/s41586-018-0305-x}, pmid = {29955152}, issn = {1476-4687}, abstract = {In the PDF version of this Letter, Andy Gardner was originally listed as a corresponding author, instead of Mauricio González-Forero. This has been corrected online.}, } @article {pmid29954989, year = {2018}, author = {Huber, L and Suzuki, R and Krüger, T and Frey, E and Bausch, AR}, title = {Emergence of coexisting ordered states in active matter systems.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {255-258}, doi = {10.1126/science.aao5434}, pmid = {29954989}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Active systems can produce a far greater variety of ordered patterns than conventional equilibrium systems. In particular, transitions between disorder and either polar- or nematically ordered phases have been predicted and observed in two-dimensional active systems. However, coexistence between phases of different types of order has not been reported. We demonstrate the emergence of dynamic coexistence of ordered states with fluctuating nematic and polar symmetry in an actomyosin motility assay. Combining experiments with agent-based simulations, we identify sufficiently weak interactions that lack a clear alignment symmetry as a prerequisite for coexistence. Thus, the symmetry of macroscopic order becomes an emergent and dynamic property of the active system. These results provide a pathway by which living systems can express different types of order by using identical building blocks.}, } @article {pmid29954988, year = {2018}, author = {Yoo, J and Wu, M and Yin, Y and Herzik, MA and Lander, GC and Lee, SY}, title = {Cryo-EM structure of a mitochondrial calcium uniporter.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {506-511}, pmid = {29954988}, issn = {1095-9203}, support = {DP2 EB020402/EB/NIBIB NIH HHS/United States ; R21 AR072910/AR/NIAMS NIH HHS/United States ; R35 NS097241/NS/NINDS NIH HHS/United States ; S10 OD021634/OD/NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Calcium/*metabolism ; Calcium Channels/*chemistry/genetics/metabolism/ultrastructure ; Conserved Sequence ; Cryoelectron Microscopy ; Fungal Proteins/*chemistry/genetics/metabolism/ultrastructure ; Models, Chemical ; Mutagenesis ; Neurospora crassa/*metabolism ; Protein Conformation ; Protein Multimerization ; }, abstract = {Calcium transport plays an important role in regulating mitochondrial physiology and pathophysiology. The mitochondrial calcium uniporter (MCU) is a calcium-selective ion channel that is the primary mediator for calcium uptake into the mitochondrial matrix. Here, we present the cryo-electron microscopy structure of the full-length MCU from Neurospora crassa to an overall resolution of ~3.7 angstroms. Our structure reveals a tetrameric architecture, with the soluble and transmembrane domains adopting different symmetric arrangements within the channel. The conserved W-D-Φ-Φ-E-P-V-T-Y sequence motif of MCU pore forms a selectivity filter comprising two acidic rings separated by one helical turn along the central axis of the channel pore. The structure combined with mutagenesis gives insight into the basis of calcium recognition.}, } @article {pmid29954987, year = {2018}, author = {Ahn, SJ and Moon, P and Kim, TH and Kim, HW and Shin, HC and Kim, EH and Cha, HW and Kahng, SJ and Kim, P and Koshino, M and Son, YW and Yang, CW and Ahn, JR}, title = {Dirac electrons in a dodecagonal graphene quasicrystal.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6404}, pages = {782-786}, doi = {10.1126/science.aar8412}, pmid = {29954987}, issn = {1095-9203}, abstract = {Quantum states of quasiparticles in solids are dictated by symmetry. We have experimentally demonstrated quantum states of Dirac electrons in a two-dimensional quasicrystal without translational symmetry. A dodecagonal quasicrystalline order was realized by epitaxial growth of twisted bilayer graphene rotated exactly 30°. We grew the graphene quasicrystal up to a millimeter scale on a silicon carbide surface while maintaining the single rotation angle over an entire sample and successfully isolated the quasicrystal from a substrate, demonstrating its structural and chemical stability under ambient conditions. Multiple Dirac cones replicated with the 12-fold rotational symmetry were observed in angle-resolved photoemission spectra, which revealed anomalous strong interlayer coupling with quasi-periodicity. Our study provides a way to explore physical properties of relativistic fermions with controllable quasicrystalline orders.}, } @article {pmid29954986, year = {2018}, author = {Gong, X and Qian, H and Cao, P and Zhao, X and Zhou, Q and Lei, J and Yan, N}, title = {Structural basis for the recognition of Sonic Hedgehog by human Patched1.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {}, doi = {10.1126/science.aas8935}, pmid = {29954986}, issn = {1095-9203}, mesh = {Binding Sites ; Cholesterol/*chemistry ; Cholesterol Esters/chemistry ; Cryoelectron Microscopy ; Hedgehog Proteins/*chemistry ; Humans ; Ligands ; Patched-1 Receptor/*chemistry/genetics ; Point Mutation ; Protein Interaction Domains and Motifs ; *Protein Interaction Maps ; }, abstract = {The Hedgehog (Hh) pathway involved in development and regeneration is activated by the extracellular binding of Hh to the membrane receptor Patched (Ptch). We report the structures of human Ptch1 alone and in complex with the N-terminal domain of human Sonic hedgehog (ShhN) at resolutions of 3.9 and 3.6 angstroms, respectively, as determined by cryo-electron microscopy. Ptch1 comprises two interacting extracellular domains, ECD1 and ECD2, and 12 transmembrane segments (TMs), with TMs 2 to 6 constituting the sterol-sensing domain (SSD). Two steroid-shaped densities are resolved in both structures, one enclosed by ECD1/2 and the other in the membrane-facing cavity of the SSD. Structure-guided mutational analysis shows that interaction between ShhN and Ptch1 is steroid-dependent. The structure of a steroid binding-deficient Ptch1 mutant displays pronounced conformational rearrangements.}, } @article {pmid29954985, year = {2018}, author = {Allen, GH and Pavelsky, TM}, title = {Global extent of rivers and streams.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {585-588}, doi = {10.1126/science.aat0636}, pmid = {29954985}, issn = {1095-9203}, abstract = {The turbulent surfaces of rivers and streams are natural hotspots of biogeochemical exchange with the atmosphere. At the global scale, the total river-atmosphere flux of trace gasses such as carbon dioxide depends on the proportion of Earth's surface that is covered by the fluvial network, yet the total surface area of rivers and streams is poorly constrained. We used a global database of planform river hydromorphology and a statistical approach to show that global river and stream surface area at mean annual discharge is 773,000 ± 79,000 square kilometers (0.58 ± 0.06%) of Earth's nonglaciated land surface, an area 44 ± 15% larger than previous spatial estimates. We found that rivers and streams likely play a greater role in controlling land-atmosphere fluxes than is currently represented in global carbon budgets.}, } @article {pmid29954982, year = {2018}, author = {Kikis, EA}, title = {The cost of a career.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1478}, doi = {10.1126/science.360.6396.1478}, pmid = {29954982}, issn = {1095-9203}, } @article {pmid29954981, year = {2018}, author = {Levari, DE and Gilbert, DT and Wilson, TD and Sievers, B and Amodio, DM and Wheatley, T}, title = {Prevalence-induced concept change in human judgment.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1465-1467}, doi = {10.1126/science.aap8731}, pmid = {29954981}, issn = {1095-9203}, mesh = {*Concept Formation ; Face ; Facial Expression ; Humans ; Judgment/*physiology ; Photic Stimulation ; Prevalence ; Social Problems/*psychology ; }, abstract = {Why do some social problems seem so intractable? In a series of experiments, we show that people often respond to decreases in the prevalence of a stimulus by expanding their concept of it. When blue dots became rare, participants began to see purple dots as blue; when threatening faces became rare, participants began to see neutral faces as threatening; and when unethical requests became rare, participants began to see innocuous requests as unethical. This "prevalence-induced concept change" occurred even when participants were forewarned about it and even when they were instructed and paid to resist it. Social problems may seem intractable in part because reductions in their prevalence lead people to see more of them.}, } @article {pmid29954980, year = {2018}, author = {Einav, L and Finkelstein, A and Mullainathan, S and Obermeyer, Z}, title = {Predictive modeling of U.S. health care spending in late life.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1462-1465}, pmid = {29954980}, issn = {1095-9203}, support = {DP5 OD012161/OD/NIH HHS/United States ; R01 AG032449/AG/NIA NIH HHS/United States ; R56 AG055728/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Health Expenditures/*trends ; Humans ; Medicare/*economics ; *Models, Economic ; Mortality/*trends ; Prognosis ; Risk ; Survivors/statistics & numerical data ; United States ; }, abstract = {That one-quarter of Medicare spending in the United States occurs in the last year of life is commonly interpreted as waste. But this interpretation presumes knowledge of who will die and when. Here we analyze how spending is distributed by predicted mortality, based on a machine-learning model of annual mortality risk built using Medicare claims. Death is highly unpredictable. Less than 5% of spending is accounted for by individuals with predicted mortality above 50%. The simple fact that we spend more on the sick-both on those who recover and those who die-accounts for 30 to 50% of the concentration of spending on the dead. Our results suggest that spending on the ex post dead does not necessarily mean that we spend on the ex ante "hopeless."}, } @article {pmid29954979, year = {2018}, author = {Barbi, E and Lagona, F and Marsili, M and Vaupel, JW and Wachter, KW}, title = {The plateau of human mortality: Demography of longevity pioneers.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1459-1461}, doi = {10.1126/science.aat3119}, pmid = {29954979}, issn = {1095-9203}, support = {P30 AG012839/AG/NIA NIH HHS/United States ; }, mesh = {Aged, 80 and over ; *Demography ; Female ; Humans ; Italy/epidemiology ; *Longevity ; Male ; Mortality/*trends ; Proportional Hazards Models ; }, abstract = {Theories about biological limits to life span and evolutionary shaping of human longevity depend on facts about mortality at extreme ages, but these facts have remained a matter of debate. Do hazard curves typically level out into high plateaus eventually, as seen in other species, or do exponential increases persist? In this study, we estimated hazard rates from data on all inhabitants of Italy aged 105 and older between 2009 and 2015 (born 1896-1910), a total of 3836 documented cases. We observed level hazard curves, which were essentially constant beyond age 105. Our estimates are free from artifacts of aggregation that limited earlier studies and provide the best evidence to date for the existence of extreme-age mortality plateaus in humans.}, } @article {pmid29954978, year = {2018}, author = {Mukhopadhyay, S and Parker, DS and Sales, BC and Puretzky, AA and McGuire, MA and Lindsay, L}, title = {Two-channel model for ultralow thermal conductivity of crystalline Tl3VSe4.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1455-1458}, doi = {10.1126/science.aar8072}, pmid = {29954978}, issn = {1095-9203}, abstract = {Solids with ultralow thermal conductivity are of great interest as thermal barrier coatings for insulation or thermoelectrics for energy conversion. However, the theoretical limits of lattice thermal conductivity (κ) are unclear. In typical crystals a phonon picture is valid, whereas lowest κ values occur in highly disordered materials where this picture fails and heat is supposedly carried by random walk among uncorrelated oscillators. Here we identify a simple crystal, Tl3VSe4, with a calculated phonon κ [0.16 Watts per meter-Kelvin (W/m-K)] one-half that of our measured κ (0.30 W/m-K) at 300 K, approaching disorder κ values, although Raman spectra, specific heat, and temperature dependence of κ reveal typical phonon characteristics. Adding a transport component based on uncorrelated oscillators explains the measured κ and suggests that a two-channel model is necessary for crystals with ultralow κ.}, } @article {pmid29954977, year = {2018}, author = {Mo, MZ and Chen, Z and Li, RK and Dunning, M and Witte, BBL and Baldwin, JK and Fletcher, LB and Kim, JB and Ng, A and Redmer, R and Reid, AH and Shekhar, P and Shen, XZ and Shen, M and Sokolowski-Tinten, K and Tsui, YY and Wang, YQ and Zheng, Q and Wang, XJ and Glenzer, SH}, title = {Heterogeneous to homogeneous melting transition visualized with ultrafast electron diffraction.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1451-1455}, doi = {10.1126/science.aar2058}, pmid = {29954977}, issn = {1095-9203}, abstract = {The ultrafast laser excitation of matters leads to nonequilibrium states with complex solid-liquid phase-transition dynamics. We used electron diffraction at mega-electron volt energies to visualize the ultrafast melting of gold on the atomic scale length. For energy densities approaching the irreversible melting regime, we first observed heterogeneous melting on time scales of 100 to 1000 picoseconds, transitioning to homogeneous melting that occurs catastrophically within 10 to 20 picoseconds at higher energy densities. We showed evidence for the heterogeneous coexistence of solid and liquid. We determined the ion and electron temperature evolution and found superheated conditions. Our results constrain the electron-ion coupling rate, determine the Debye temperature, and reveal the melting sensitivity to nucleation seeds.}, } @article {pmid29954976, year = {2018}, author = {Hong, G and Fu, TM and Qiao, M and Viveros, RD and Yang, X and Zhou, T and Lee, JM and Park, HG and Sanes, JR and Lieber, CM}, title = {A method for single-neuron chronic recording from the retina in awake mice.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1447-1451}, pmid = {29954976}, issn = {1095-9203}, support = {DP1 EB025835/EB/NIBIB NIH HHS/United States ; K99 AG056636/AG/NIA NIH HHS/United States ; R37 NS029169/NS/NINDS NIH HHS/United States ; R37 NS029169/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Circadian Rhythm ; *Electrodes, Implanted ; Mice ; Microelectrodes ; Neural Pathways/physiology ; Photic Stimulation ; Retinal Ganglion Cells/*physiology ; Single-Cell Analysis/*methods ; Wakefulness ; }, abstract = {The retina, which processes visual information and sends it to the brain, is an excellent model for studying neural circuitry. It has been probed extensively ex vivo but has been refractory to chronic in vivo electrophysiology. We report a nonsurgical method to achieve chronically stable in vivo recordings from single retinal ganglion cells (RGCs) in awake mice. We developed a noncoaxial intravitreal injection scheme in which injected mesh electronics unrolls inside the eye and conformally coats the highly curved retina without compromising normal eye functions. The method allows 16-channel recordings from multiple types of RGCs with stable responses to visual stimuli for at least 2 weeks, and reveals circadian rhythms in RGC responses over multiple day/night cycles.}, } @article {pmid29954975, year = {2018}, author = {Luo, D and Yang, W and Wang, Z and Sadhanala, A and Hu, Q and Su, R and Shivanna, R and Trindade, GF and Watts, JF and Xu, Z and Liu, T and Chen, K and Ye, F and Wu, P and Zhao, L and Wu, J and Tu, Y and Zhang, Y and Yang, X and Zhang, W and Friend, RH and Gong, Q and Snaith, HJ and Zhu, R}, title = {Enhanced photovoltage for inverted planar heterojunction perovskite solar cells.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1442-1446}, doi = {10.1126/science.aap9282}, pmid = {29954975}, issn = {1095-9203}, abstract = {The highest power conversion efficiencies (PCEs) reported for perovskite solar cells (PSCs) with inverted planar structures are still inferior to those of PSCs with regular structures, mainly because of lower open-circuit voltages (Voc). Here we report a strategy to reduce nonradiative recombination for the inverted devices, based on a simple solution-processed secondary growth technique. This approach produces a wider bandgap top layer and a more n-type perovskite film, which mitigates nonradiative recombination, leading to an increase in Voc by up to 100 millivolts. We achieved a high Voc of 1.21 volts without sacrificing photocurrent, corresponding to a voltage deficit of 0.41 volts at a bandgap of 1.62 electron volts. This improvement led to a stabilized power output approaching 21% at the maximum power point.}, } @article {pmid29954974, year = {2018}, author = {Chen, J and Gong, X and Li, J and Li, Y and Ma, J and Hou, C and Zhao, G and Yuan, W and Zhao, B}, title = {Carbonyl catalysis enables a biomimetic asymmetric Mannich reaction.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1438-1442}, doi = {10.1126/science.aat4210}, pmid = {29954974}, issn = {1095-9203}, mesh = {Amines/*chemistry ; Biomimetic Materials/*chemical synthesis ; Catalysis ; Imines/*chemistry ; }, abstract = {Chiral amines are widely used as catalysts in asymmetric synthesis to activate carbonyl groups for α-functionalization. Carbonyl catalysis reverses that strategy by using a carbonyl group to activate a primary amine. Inspired by biological carbonyl catalysis, which is exemplified by reactions of pyridoxal-dependent enzymes, we developed an N-quaternized pyridoxal catalyst for the asymmetric Mannich reaction of glycinate with aryl N-diphenylphosphinyl imines. The catalyst exhibits high activity and stereoselectivity, likely enabled by enzyme-like cooperative bifunctional activation of the substrates. Our work demonstrates the catalytic utility of the pyridoxal moiety in asymmetric catalysis.}, } @article {pmid29954973, year = {2018}, author = {Yu, J and Jackson, NE and Xu, X and Morgenstern, Y and Kaufman, Y and Ruths, M and de Pablo, JJ and Tirrell, M}, title = {Multivalent counterions diminish the lubricity of polyelectrolyte brushes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1434-1438}, doi = {10.1126/science.aar5877}, pmid = {29954973}, issn = {1095-9203}, abstract = {Polyelectrolyte brushes provide wear protection and lubrication in many technical, medical, physiological, and biological applications. Wear resistance and low friction are attributed to counterion osmotic pressure and the hydration layer surrounding the charged polymer segments. However, the presence of multivalent counterions in solution can strongly affect the interchain interactions and structural properties of brush layers. We evaluated the lubrication properties of polystyrene sulfonate brush layers sliding against each other in aqueous solutions containing increasing concentrations of counterions. The presence of multivalent ions (Y3+, Ca2+, Ba2+), even at minute concentrations, markedly increases the friction forces between brush layers owing to electrostatic bridging and brush collapse. Our results suggest that the lubricating properties of polyelectrolyte brushes in multivalent solution are hindered relative to those in monovalent solution.}, } @article {pmid29954972, year = {2018}, author = {Sugawa, S and Salces-Carcoba, F and Perry, AR and Yue, Y and Spielman, IB}, title = {Second Chern number of a quantum-simulated non-Abelian Yang monopole.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1429-1434}, doi = {10.1126/science.aam9031}, pmid = {29954972}, issn = {1095-9203}, abstract = {Topological order is often quantified in terms of Chern numbers, each of which classifies a topological singularity. Here, inspired by concepts from high-energy physics, we use quantum simulation based on the spin degrees of freedom of atomic Bose-Einstein condensates to characterize a singularity present in five-dimensional non-Abelian gauge theories-a Yang monopole. We quantify the monopole in terms of Chern numbers measured on enclosing manifolds: Whereas the well-known first Chern number vanishes, the second Chern number does not. By displacing the manifold, we induce and observe a topological transition, where the topology of the manifold changes to a trivial state.}, } @article {pmid29954971, year = {2018}, author = {Pietrzak, B and Ward, A and Cheung, MK and Schwendimann, BA and Mollaoglu, G and Duong, MT and Ulltveit-Moe, N and Allareddy, V and Dutton-Regester, K and Zhang, J and Scult, MA and Naz, S and Singh, PC and Yan, HY and Isaacson, K and Dennis, AF and Al-Humaidan, EI and Beardsley, FR and Lo, C and Sood, P and Jones, T and Nieuwenhuis, R and Ali, BA and Yu, KH and Arthur, PK and Kumar, B and Chen, A and Buschke, F and Cingl, L and Zaidi, SS and O'Mullane, AP and Coetzee, V and Konstantinides, N}, title = {Education for the future.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1409-1412}, doi = {10.1126/science.aau3877}, pmid = {29954971}, issn = {1095-9203}, } @article {pmid29954970, year = {2018}, author = {Prathapan, KD and Pethiyagoda, R and Bawa, KS and Raven, PH and Rajan, PD and , }, title = {When the cure kills-CBD limits biodiversity research.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1405-1406}, doi = {10.1126/science.aat9844}, pmid = {29954970}, issn = {1095-9203}, mesh = {*Biodiversity ; Classification ; *Conservation of Natural Resources ; Human Activities ; Research ; }, } @article {pmid29954969, year = {2018}, author = {Arber, S and Costa, RM}, title = {Connecting neuronal circuits for movement.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1403-1404}, doi = {10.1126/science.aat5994}, pmid = {29954969}, issn = {1095-9203}, mesh = {Animals ; Brain/*physiology/ultrastructure ; Humans ; Movement/*physiology ; Neural Pathways/*physiology ; Neurons/*physiology ; }, } @article {pmid29954968, year = {2018}, author = {Kannan, N and Eaves, CJ}, title = {Macrophages stimulate mammary stem cells.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1401-1402}, pmid = {29954968}, issn = {1095-9203}, support = {P50 CA116201/CA/NCI NIH HHS/United States ; }, mesh = {Epithelial Cells ; *Macrophages ; *Stem Cells ; }, } @article {pmid29954967, year = {2018}, author = {Lécuyer, C}, title = {Learning from past climatic changes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1400-1401}, doi = {10.1126/science.aau1690}, pmid = {29954967}, issn = {1095-9203}, mesh = {*Climate ; Climate Change ; *Ecosystem ; }, } @article {pmid29954966, year = {2018}, author = {Ballauff, M}, title = {More friction for polyelectrolyte brushes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1399-1400}, doi = {10.1126/science.aat5343}, pmid = {29954966}, issn = {1095-9203}, mesh = {*Friction ; *Polyelectrolytes ; Polymers ; Surface Properties ; }, } @article {pmid29954965, year = {2018}, author = {Olivetti, EA and Cullen, JM}, title = {Toward a sustainable materials system.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1396-1398}, doi = {10.1126/science.aat6821}, pmid = {29954965}, issn = {1095-9203}, } @article {pmid29954964, year = {2018}, author = {Grimm, D}, title = {Opening the lab door.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1392-1395}, doi = {10.1126/science.360.6396.1392}, pmid = {29954964}, issn = {1095-9203}, mesh = {*Access to Information ; Animal Experimentation/*ethics ; *Animal Rights ; Animals ; Dogs ; Haplorhini ; }, } @article {pmid29954963, year = {2018}, author = {Pennisi, E}, title = {Is cancer a breakdown of multicellularity?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1391}, doi = {10.1126/science.360.6396.1391}, pmid = {29954963}, issn = {1095-9203}, mesh = {*Biological Evolution ; Carcinogenesis/genetics/*pathology ; Gene Regulatory Networks ; Humans ; Neoplasms/genetics/*pathology ; }, } @article {pmid29954962, year = {2018}, author = {Pennisi, E}, title = {The power of many.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1388-1391}, doi = {10.1126/science.360.6396.1388}, pmid = {29954962}, issn = {1095-9203}, mesh = {*Biological Evolution ; *Cell Count ; *Cells ; Chlamydomonas/cytology ; Volvox/cytology ; Yeasts/cytology ; }, } @article {pmid29954961, year = {2018}, author = {Garber, K}, title = {Blood test may predict cancer immunotherapy benefit.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1387}, doi = {10.1126/science.360.6396.1387}, pmid = {29954961}, issn = {1095-9203}, mesh = {DNA Mutational Analysis/*methods ; *Hematologic Tests ; Humans ; *Immunotherapy ; Neoplasm Proteins/*genetics ; Neoplasms/*genetics/*therapy ; Predictive Value of Tests ; Treatment Outcome ; }, } @article {pmid29954960, year = {2018}, author = {Service, RF}, title = {See-through solar cells could power offices.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1386}, doi = {10.1126/science.360.6396.1386}, pmid = {29954960}, issn = {1095-9203}, } @article {pmid29954959, year = {2018}, author = {Wadman, M}, title = {Newborn screening urged for fatal neurological disorder.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1385}, doi = {10.1126/science.360.6396.1385}, pmid = {29954959}, issn = {1095-9203}, mesh = {Device Approval ; Humans ; Infant, Newborn ; Muscular Atrophy, Spinal/*diagnosis ; *Neonatal Screening ; United States ; }, } @article {pmid29954958, year = {2018}, author = {Nordling, L}, title = {In Nigeria, a battle against plagiarism heats up.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1384-1385}, doi = {10.1126/science.360.6396.1384}, pmid = {29954958}, issn = {1095-9203}, } @article {pmid29954957, year = {2018}, author = {Chen, S}, title = {Random number generators go public.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1383-1384}, doi = {10.1126/science.360.6396.1383}, pmid = {29954957}, issn = {1095-9203}, } @article {pmid29954956, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1380-1382}, doi = {10.1126/science.360.6396.1380}, pmid = {29954956}, issn = {1095-9203}, } @article {pmid29954955, year = {2018}, author = {Berg, J}, title = {Tomorrow's Earth.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1379}, doi = {10.1126/science.aau5515}, pmid = {29954955}, issn = {1095-9203}, } @article {pmid29954954, year = {2018}, author = {Davis, SJ and Lewis, NS and Shaner, M and Aggarwal, S and Arent, D and Azevedo, IL and Benson, SM and Bradley, T and Brouwer, J and Chiang, YM and Clack, CTM and Cohen, A and Doig, S and Edmonds, J and Fennell, P and Field, CB and Hannegan, B and Hodge, BM and Hoffert, MI and Ingersoll, E and Jaramillo, P and Lackner, KS and Mach, KJ and Mastrandrea, M and Ogden, J and Peterson, PF and Sanchez, DL and Sperling, D and Stagner, J and Trancik, JE and Yang, CJ and Caldeira, K}, title = {Net-zero emissions energy systems.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {}, doi = {10.1126/science.aas9793}, pmid = {29954954}, issn = {1095-9203}, abstract = {Some energy services and industrial processes-such as long-distance freight transport, air travel, highly reliable electricity, and steel and cement manufacturing-are particularly difficult to provide without adding carbon dioxide (CO2) to the atmosphere. Rapidly growing demand for these services, combined with long lead times for technology development and long lifetimes of energy infrastructure, make decarbonization of these services both essential and urgent. We examine barriers and opportunities associated with these difficult-to-decarbonize services and processes, including possible technological solutions and research and development priorities. A range of existing technologies could meet future demands for these services and processes without net addition of CO2 to the atmosphere, but their use may depend on a combination of cost reductions via research and innovation, as well as coordinated deployment and integration of operations across currently discrete energy industries.}, } @article {pmid29954866, year = {2018}, author = {Strangward, P and Haley, MJ and Albornoz, MG and Barrington, J and Shaw, T and Dookie, R and Zeef, L and Baker, SM and Winter, E and Tzeng, TC and Golenbock, DT and Cruickshank, SM and Allan, SM and Craig, A and Liew, FY and Brough, D and Couper, KN}, title = {Targeting the IL33-NLRP3 axis improves therapy for experimental cerebral malaria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7404-7409}, pmid = {29954866}, issn = {1091-6490}, support = {G0900487//Medical Research Council/United Kingdom ; R01 AI079293/AI/NIAID NIH HHS/United States ; MR/L008564/1//Medical Research Council/United Kingdom ; MR/R010099/1//Medical Research Council/United Kingdom ; MC_PC_16033//Medical Research Council/United Kingdom ; MR/N003586/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Antimalarials/*pharmacology ; Brain/metabolism/*parasitology/pathology ; Disease Models, Animal ; Drug Delivery Systems/*methods ; Female ; Gene Expression Profiling ; Hemeproteins/metabolism ; Interleukin-1beta/biosynthesis ; Interleukin-33/antagonists & inhibitors/*metabolism ; Macrophages/metabolism/pathology ; Malaria, Cerebral/*drug therapy/metabolism/pathology ; Malaria, Falciparum/*drug therapy/metabolism/pathology ; Male ; Mice ; NLR Family, Pyrin Domain-Containing 3 Protein/antagonists & inhibitors/*metabolism ; Plasmodium falciparum/*metabolism ; Transcriptome/drug effects ; }, abstract = {Cerebral malaria (CM) is a serious neurological complication caused by Plasmodium falciparum infection. Currently, the only treatment for CM is the provision of antimalarial drugs; however, such treatment by itself often fails to prevent death or development of neurological sequelae. To identify potential improved treatments for CM, we performed a nonbiased whole-brain transcriptomic time-course analysis of antimalarial drug chemotherapy of murine experimental CM (ECM). Bioinformatics analyses revealed IL33 as a critical regulator of neuroinflammation and cerebral pathology that is down-regulated in the brain during fatal ECM and in the acute period following treatment of ECM. Consistent with this, administration of IL33 alongside antimalarial drugs significantly improved the treatment success of established ECM. Mechanistically, IL33 treatment reduced inflammasome activation and IL1β production in microglia and intracerebral monocytes in the acute recovery period following treatment of ECM. Moreover, treatment with the NLRP3-inflammasome inhibitor MCC950 alongside antimalarial drugs phenocopied the protective effect of IL33 therapy in improving the recovery from established ECM. We further showed that IL1β release from macrophages was stimulated by hemozoin and antimalarial drugs and that this was inhibited by MCC950. Our results therefore demonstrate that manipulation of the IL33-NLRP3 axis may be an effective therapy to suppress neuroinflammation and improve the efficacy of antimalarial drug treatment of CM.}, } @article {pmid29954865, year = {2018}, author = {Charpentier, CJ and Bromberg-Martin, ES and Sharot, T}, title = {Valuation of knowledge and ignorance in mesolimbic reward circuitry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7255-E7264}, pmid = {29954865}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 MH110594/MH/NIMH NIH HHS/United States ; }, mesh = {Humans ; *Knowledge ; Limbic System/*physiology ; Neural Pathways/physiology ; Nucleus Accumbens/physiology ; Prefrontal Cortex/physiology ; *Reward ; Ventral Tegmental Area/physiology ; }, abstract = {The pursuit of knowledge is a basic feature of human nature. However, in domains ranging from health to finance people sometimes choose to remain ignorant. Here, we show that valence is central to the process by which the human brain evaluates the opportunity to gain information, explaining why knowledge may not always be preferred. We reveal that the mesolimbic reward circuitry selectively treats the opportunity to gain knowledge about future favorable outcomes, but not unfavorable outcomes, as if it has positive utility. This neural coding predicts participants' tendency to choose knowledge about future desirable outcomes more often than undesirable ones, and to choose ignorance about future undesirable outcomes more often than desirable ones. Strikingly, participants are willing to pay both for knowledge and ignorance as a function of the expected valence of knowledge. The orbitofrontal cortex (OFC), however, responds to the opportunity to receive knowledge over ignorance regardless of the valence of the information. Connectivity between the OFC and mesolimbic circuitry could contribute to a general preference for knowledge that is also modulated by valence. Our findings characterize the importance of valence in information seeking and its underlying neural computation. This mechanism could lead to suboptimal behavior, such as when people reject medical screenings or monitor investments more during bull than bear markets.}, } @article {pmid29954864, year = {2018}, author = {Lavrentovich, OD}, title = {Prepatterned liquid crystal elastomers as a step toward artificial morphogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7171-7173}, pmid = {29954864}, issn = {1091-6490}, mesh = {*Elastomers ; *Liquid Crystals ; Morphogenesis ; }, } @article {pmid29954863, year = {2018}, author = {Saelices, L and Chung, K and Lee, JH and Cohn, W and Whitelegge, JP and Benson, MD and Eisenberg, DS}, title = {Amyloid seeding of transthyretin by ex vivo cardiac fibrils and its inhibition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6741-E6750}, pmid = {29954863}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Amyloid/*chemistry/metabolism ; Amyloid Neuropathies, Familial/metabolism/pathology ; Female ; Humans ; Hydrogen-Ion Concentration ; Male ; Myocardium/*chemistry/metabolism/pathology ; Prealbumin/*chemistry/metabolism ; }, abstract = {Each of the 30 human amyloid diseases is associated with the aggregation of a particular precursor protein into amyloid fibrils. In transthyretin amyloidosis (ATTR), mutant or wild-type forms of the serum carrier protein transthyretin (TTR), synthesized and secreted by the liver, convert to amyloid fibrils deposited in the heart and other organs. The current standard of care for hereditary ATTR is liver transplantation, which replaces the mutant TTR gene with the wild-type gene. However, the procedure is often followed by cardiac deposition of wild-type TTR secreted by the new liver. Here we find that amyloid fibrils extracted from autopsied and explanted hearts of ATTR patients robustly seed wild-type TTR into amyloid fibrils in vitro. Cardiac-derived ATTR seeds can accelerate fibril formation of wild-type and monomeric TTR at acidic pH and under physiological conditions, respectively. We show that this seeding is inhibited by peptides designed to complement structures of TTR fibrils. These inhibitors cap fibril growth, suggesting an approach for halting progression of ATTR.}, } @article {pmid29954862, year = {2018}, author = {Aleman, F and Tzarum, N and Kong, L and Nagy, K and Zhu, J and Wilson, IA and Law, M}, title = {Immunogenetic and structural analysis of a class of HCV broadly neutralizing antibodies and their precursors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7569-7574}, pmid = {29954862}, issn = {1091-6490}, support = {R01 AI106005/AI/NIAID NIH HHS/United States ; R01 AI079031/AI/NIAID NIH HHS/United States ; P41 RR001209/RR/NCRR NIH HHS/United States ; R01 AI123365/AI/NIAID NIH HHS/United States ; R56 AI106005/AI/NIAID NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; U19 AI123861/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Neutralizing/*chemistry/immunology ; Cell Line ; Hepacivirus/*chemistry/immunology ; Hepatitis C Antibodies/*chemistry/immunology ; Humans ; Immunoglobulin Light Chains/*chemistry/immunology ; Mice ; Single-Chain Antibodies/*chemistry/immunology ; Viral Envelope Proteins/*chemistry/immunology ; Viral Hepatitis Vaccines/chemistry/immunology ; }, abstract = {Elicitation of broadly neutralizing antibodies (bnAbs) is a leading strategy in rational vaccine design against antigenically diverse pathogens. Here, we studied a panel of monoclonal antibodies (mAbs) from mice immunized with the hepatitis C virus (HCV) envelope glycoproteins E1E2. Six of the mAbs recognize the conserved E2 antigenic site 412-423 (AS412) and cross-neutralize diverse HCV genotypes. Immunogenetic and structural analysis revealed that the antibodies originated from two different germline (GL) precursors and bind AS412 in a β-hairpin conformation. Intriguingly, the anti-HCV activity of one antibody lineage is associated with maturation of the light chain (LC), whereas the other lineage is dependent on heavy-chain (HC) maturation. Crystal structures of GL precursors of the LC-dependent lineage in complex with AS412 offer critical insights into the maturation process of bnAbs to HCV, providing a scientific foundation for utilizing the mouse model to study AS412-targeting vaccine candidates.}, } @article {pmid29954861, year = {2018}, author = {McRose, DL and Baars, O and Seyedsayamdost, MR and Morel, FMM}, title = {Quorum sensing and iron regulate a two-for-one siderophore gene cluster in Vibrio harveyi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7581-7586}, pmid = {29954861}, issn = {1091-6490}, mesh = {Enterobactin/*biosynthesis/genetics ; Iron/*metabolism ; Multigene Family/*physiology ; Quorum Sensing/*physiology ; Siderophores/*biosynthesis/genetics ; Vibrio/genetics/*metabolism ; }, abstract = {The secretion of small Fe-binding molecules called siderophores is an important microbial strategy for survival in Fe-limited environments. Siderophore production is often regulated by quorum sensing (QS), a microbial counting technique that allows organisms to alter gene expression based on cell density. However, the identity and quantities of siderophores produced under QS regulation are rarely studied in the context of their roles in Fe uptake. We investigated the link between QS, siderophores, and Fe uptake in the model marine organism Vibrio harveyi where QS is thought to repress siderophore production. We find that V. harveyi uses a single QS- and Fe-repressed gene cluster to produce both cell-associated siderophores (amphiphilic enterobactins) as well as several related soluble siderophores, which we identify and quantify using liquid chromatography-coupled (LC)-MS as well as tandem high-resolution MS (LC-HR-MS/MS). Measurements of siderophore production show that soluble siderophores are present at ∼100× higher concentrations than amphi-enterobactin and that over the course of growth V. harveyi decreases amphi-enterobactin concentrations but accumulates soluble siderophores. 55Fe radio-tracer uptake experiments demonstrate that these soluble siderophores play a significant role in Fe uptake and that the QS-dictated concentrations of soluble siderophores in stationary phase are near the limit of cellular uptake capacities. We propose that cell-associated and soluble siderophores are beneficial to V. harveyi in different environmental and growth contexts and that QS allows V. harveyi to exploit "knowledge" of its population size to avoid unnecessary siderophore production.}, } @article {pmid29954660, year = {2018}, author = {Kahl, J and Brattig, N and Liebau, E}, title = {The Untapped Pharmacopeic Potential of Helminths.}, journal = {Trends in parasitology}, volume = {34}, number = {10}, pages = {828-842}, doi = {10.1016/j.pt.2018.05.011}, pmid = {29954660}, issn = {1471-5007}, mesh = {Animals ; Antigens, Helminth/immunology/pharmacology ; Disease Models, Animal ; Drug Discovery/*trends ; Helminths/*chemistry ; Immune System/drug effects ; Immunologic Factors/chemistry/*immunology/standards ; }, abstract = {The dramatic rise in immunological disorders that occurs with socioeconomic development is associated with alterations in microbial colonization and reduced exposure to helminths. Excretory-secretory (E/S) helminth products contain a mixture of proteins and low-molecular-weight molecules representing the primary interface between parasite and host. Research has shown great pharmacopeic potential for helminth-derived products in animal disease models and even in clinical trials. Although in its infancy, the translation of worm-derived products into therapeutics is highly promising. Here, we focus on important key aspects in the development of immunomodulatory drugs, also highlighting novel approaches that hold great promise for future development of innovative research strategies.}, } @article {pmid29954653, year = {2018}, author = {Tanner, JR and Kingsley, RA}, title = {Evolution of Salmonella within Hosts.}, journal = {Trends in microbiology}, volume = {26}, number = {12}, pages = {986-998}, pmid = {29954653}, issn = {1878-4380}, abstract = {Within-host evolution has resulted in thousands of variants of Salmonella that exhibit remarkable diversity in host range and disease outcome, from broad host range to exquisite host restriction, causing gastroenteritis to disseminated disease such as typhoid fever. Within-host evolution is a continuing process driven by genomic variation that occurs during each infection, potentiating adaptation to a new niche resulting from changes in animal husbandry, the use of antimicrobials, and emergence of immune compromised populations. We discuss key advances in our understanding of the evolution of Salmonella within the host, inferred from (i) the process of host adaptation of Salmonella pathovars in the past, and (ii) direct observation of the generation of variation and selection of beneficial traits during single infections.}, } @article {pmid29954592, year = {2018}, author = {Gilbert, CC and Frost, SR and Pugh, KD and Anderson, M and Delson, E}, title = {Evolution of the modern baboon (Papio hamadryas): A reassessment of the African Plio-Pleistocene record.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {38-69}, doi = {10.1016/j.jhevol.2018.04.012}, pmid = {29954592}, issn = {1095-8606}, abstract = {Baboons (Papio hamadryas) are among the most successful extant primates, with a minimum of six distinctive forms throughout Sub-Saharan Africa. However, their presence in the fossil record is unclear. Three early fossil taxa are generally recognized, all from South Africa: Papio izodi, Papio robinsoni and Papio angusticeps. Because of their derived appearance, P. angusticeps and P. robinsoni have sometimes been considered subspecies of P. hamadryas and have been used as biochronological markers for the Plio-Pleistocene hominin sites where they are found. We reexamined fossil Papio forms from across Africa with an emphasis on their distinguishing features and distribution. We find that P. robinsoni and P. angusticeps are distinct from each other in several cranial features, but overlap extensively in dental size. Contrary to previous assessments, no diagnostic cranio-mandibular material suggests these two forms co-occur, and dental variation at each site is comparable to that within P. h. ursinus, suggesting that only one form is present in each case. P izodi, however, may co-occur with P. robinsoni, or another Papio form, at Sterkfontein Member 4. P izodi appears more primitive than P. robinsoni and P. angusticeps. P. robinsoni is slightly distinct from P. hamadryas subspecies in its combination of features while P. angusticeps might be included within one of the modern P. hamadryas varieties (i.e., P. h. angusticeps). No definitive Papio fossils are currently documented in eastern Africa until the Middle Pleistocene, pointing to southern Africa as the geographic place of origin for the genus. These results have implications for Plio-Pleistocene biochronology and baboon evolution.}, } @article {pmid29954460, year = {2018}, author = {Farhan Ul Haque, M and Crombie, AT and Ensminger, SA and Baciu, C and Murrell, JC}, title = {Facultative methanotrophs are abundant at terrestrial natural gas seeps.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {118}, pmid = {29954460}, issn = {2049-2618}, mesh = {Base Sequence ; Beijerinckiaceae/*classification/genetics/*isolation & purification/metabolism ; Methane/*metabolism ; Natural Gas/*microbiology ; Oxygenases/*genetics ; Phylogeny ; Propane/metabolism ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Soil Microbiology ; }, abstract = {BACKGROUND: Natural gas contains methane and the gaseous alkanes ethane, propane and butane, which collectively influence atmospheric chemistry and cause global warming. Methane-oxidising bacteria, methanotrophs, are crucial in mitigating emissions of methane as they oxidise most of the methane produced in soils and the subsurface before it reaches the atmosphere. Methanotrophs are usually obligate, i.e. grow only on methane and not on longer chain alkanes. Bacteria that grow on the other gaseous alkanes in natural gas such as propane have also been characterised, but they do not grow on methane. Recently, it was shown that the facultative methanotroph Methylocella silvestris grew on ethane and propane, other components of natural gas, in addition to methane. Therefore, we hypothesised that Methylocella may be prevalent at natural gas seeps and might play a major role in consuming all components of this potent greenhouse gas mixture before it is released to the atmosphere.

RESULTS: Environments known to be exposed to biogenic methane emissions or thermogenic natural gas seeps were surveyed for methanotrophs. 16S rRNA gene amplicon sequencing revealed that Methylocella were the most abundant methanotrophs in natural gas seep environments. New Methylocella-specific molecular tools targeting mmoX (encoding the soluble methane monooxygenase) by PCR and Illumina amplicon sequencing were designed and used to investigate various sites. Functional gene-based assays confirmed that Methylocella were present in all of the natural gas seep sites tested here. This might be due to its ability to use methane and other short chain alkane components of natural gas. We also observed the abundance of Methylocella in other environments exposed to biogenic methane, suggesting that Methylocella has been overlooked in the past as previous ecological studies of methanotrophs often used pmoA (encoding the alpha subunit of particulate methane monooxygenase) as a marker gene.

CONCLUSION: New biomolecular tools designed in this study have expanded our ability to detect, and our knowledge of the environmental distribution of Methylocella, a unique facultative methanotroph. This study has revealed that Methylocella are particularly abundant at natural gas seeps and may play a significant role in biogeochemical cycling of gaseous hydrocarbons.}, } @article {pmid29954459, year = {2018}, author = {Singh, SB and Odingo, J and Bailey, MA and Sunde, B and Korkegian, A and O'Malley, T and Ovechkina, Y and Ioerger, TR and Sacchettini, JC and Young, K and Olsen, DB and Parish, T}, title = {Identification of cyclic hexapeptides natural products with inhibitory potency against Mycobacterium tuberculosis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {416}, pmid = {29954459}, issn = {1756-0500}, support = {OPP1024038//Bill and Melinda Gates Foundation/ ; }, mesh = {Antitubercular Agents/*pharmacology ; Biological Products ; Humans ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis/*drug effects ; Oligopeptides/*pharmacology ; Structure-Activity Relationship ; }, abstract = {OBJECTIVE: Our aim was to identify natural products with anti-tubercular activity.

RESULTS: A set of ~ 500 purified natural product compounds was screened for inhibition against the human pathogen Mycobacterium tuberculosis. A series of cyclic hexapeptides with anti-tubercular activity was identified. Five analogs from a set of sixteen closely related compounds were active, with minimum inhibitory concentrations ranging from 2.3 to 8.9 μM. Eleven structural analogs had no significant activity (MIC > 20 μM) demonstrating structure activity relationship. Sequencing of resistant mutant isolates failed to identify changes accounting for the resistance phenotype.}, } @article {pmid29954455, year = {2018}, author = {Katsuyama, Y and Shirai, T and Terauchi, R and Tsuchida, S and Mizoshiri, N and Mori, Y and Kubo, T}, title = {Chondroid lipoma of the neck: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {415}, pmid = {29954455}, issn = {1756-0500}, mesh = {Adult ; Diagnosis, Differential ; *Head and Neck Neoplasms/diagnosis/surgery ; Humans ; *Lipoma/diagnosis/surgery ; Magnetic Resonance Imaging ; Male ; Neoplasm Recurrence, Local ; Soft Tissue Neoplasms ; }, abstract = {BACKGROUND: Chondroid lipoma, first described in 1993 by Meis and Enzinger, is a very rare lipomatous tumor. Because it is a benign tumor, it does not require radiotherapy, chemotherapy, or extensive resection. However, histologically, it is often confused with a sarcoma. It is crucial to differentiate chondroid lipoma from sarcoma to avoid choosing an inappropriate treatment strategy. Although MRI, radiography, and ultrasound have been used to evaluate chondroid lipomas, imaging cannot accurately differentiate chondroid lipoma from sarcoma.

CASE PRESENTATION: A 39-year-old man presented to a local clinic with a 1-month history of a painless mass in his left neck. Results of a needle biopsy suggested an atypical lipomatous tumor, and the patient was referred to our hospital. Physical examination revealed a hard and mobile mass in the left neck. Plain X-ray radiographs showed an absence of calcification in the soft tissue mass. MRI revealed a well-defined and lobulated mass, and on T1-weighted images, the lesion showed heterogeneity, with higher signal intensity than that of muscle. On T2-weighted images, the septum had low-signal intensity. On T2-weighted fat-suppressed images, the signal of the mass was completely suppressed. The SUVmax of the mass on FDG PET was 1.84. An additional needle biopsy was performed, and on the basis of the results, we arrived at a diagnosis of well-differentiated liposarcoma. The mass was resected marginally. Macroscopically, the mass was encapsulated and markedly harder than well-differentiated liposarcoma. Histologically, the tumor was composed of myxoid and cartilaginous matrix, and mature fat cells and lipoblast-like cells were present. The final diagnosis was chondroid lipoma, and no recurrence was observed 1 year after surgery.

CONCLUSIONS: Chondroid lipoma is an extremely rare benign soft tissue tumor that is often confused with sarcoma. It is very important to differentiate chondroid lipoma from sarcoma when the SUVmax value of the mass is low, even when biopsy results suggest that it is a sarcoma.}, } @article {pmid29954454, year = {2018}, author = {Krumbeck, JA and Rasmussen, HE and Hutkins, RW and Clarke, J and Shawron, K and Keshavarzian, A and Walter, J}, title = {Probiotic Bifidobacterium strains and galactooligosaccharides improve intestinal barrier function in obese adults but show no synergism when used together as synbiotics.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {121}, pmid = {29954454}, issn = {2049-2618}, mesh = {Adult ; Bifidobacterium/*metabolism ; Double-Blind Method ; Endotoxemia ; Female ; Gastrointestinal Microbiome/*genetics ; Humans ; Intestines/microbiology/*physiology ; Male ; Middle Aged ; Obesity ; Oligosaccharides/*pharmacology ; Prebiotics/*administration & dosage ; Probiotics/*pharmacology ; RNA, Ribosomal, 16S/genetics ; Sucrose/analogs & derivatives/metabolism ; Synbiotics/*administration & dosage ; Tight Junctions/*drug effects/*microbiology ; Young Adult ; }, abstract = {BACKGROUND: One way to improve both the ecological performance and functionality of probiotic bacteria is by combining them with a prebiotic in the form of a synbiotic. However, the degree to which such synbiotic formulations improve probiotic strain functionality in humans has not been tested systematically. Our goal was to use a randomized, double-blind, placebo-controlled, parallel-arm clinical trial in obese humans to compare the ecological and physiological impact of the prebiotic galactooligosaccharides (GOS) and the probiotic strains Bifidobacterium adolescentis IVS-1 (autochthonous and selected via in vivo selection) and Bifidobacterium lactis BB-12 (commercial probiotic allochthonous to the human gut) when used on their own or as synbiotic combinations. After 3 weeks of consumption, strain-specific quantitative real-time PCR and 16S rRNA gene sequencing were performed on fecal samples to assess changes in the microbiota. Intestinal permeability was determined by measuring sugar recovery in urine by GC after consumption of a sugar mixture. Serum-based endotoxin exposure was also assessed.

RESULTS: IVS-1 reached significantly higher cell numbers in fecal samples than BB-12 (P < 0.01) and, remarkably, its administration induced an increase in total bifidobacteria that was comparable to that of GOS. Although GOS showed a clear bifidogenic effect on the resident gut microbiota, both probiotic strains showed only a non-significant trend of higher fecal cell numbers when administered with GOS. Post-aspirin sucralose:lactulose ratios were reduced in groups IVS-1 (P = 0.050), IVS-1 + GOS (P = 0.022), and GOS (P = 0.010), while sucralose excretion was reduced with BB-12 (P = 0.002) and GOS (P = 0.020), indicating improvements in colonic permeability but no synergistic effects. No changes in markers of endotoxemia were observed.

CONCLUSION: This study demonstrated that "autochthony" of the probiotic strain has a larger effect on ecological performance than the provision of a prebiotic substrate, likely due to competitive interactions with members of the resident microbiota. Although the synbiotic combinations tested in this study did not demonstrate functional synergism, our findings clearly showed that the pro- and prebiotic components by themselves improved markers of colonic permeability, providing a rational for their use in pathologies with an underlying leakiness of the gut.}, } @article {pmid29954453, year = {2018}, author = {Parras-Moltó, M and Rodríguez-Galet, A and Suárez-Rodríguez, P and López-Bueno, A}, title = {Evaluation of bias induced by viral enrichment and random amplification protocols in metagenomic surveys of saliva DNA viruses.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {119}, pmid = {29954453}, issn = {2049-2618}, mesh = {Base Composition/genetics ; DNA Viruses/*genetics ; Genetic Markers/genetics ; Genome, Viral/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenome/*genetics ; *Metagenomics ; Microbiota/genetics ; Nucleic Acid Amplification Techniques/*methods ; Polymerase Chain Reaction ; Saliva/*virology ; }, abstract = {BACKGROUND: Viruses are key players regulating microbial ecosystems. Exploration of viral assemblages is now possible thanks to the development of metagenomics, the most powerful tool available for studying viral ecology and discovering new viruses. Unfortunately, several sources of bias lead to the misrepresentation of certain viruses within metagenomics workflows, hindering the shift from merely descriptive studies towards quantitative comparisons of communities. Therefore, benchmark studies on virus enrichment and random amplification protocols are required to better understand the sources of bias.

RESULTS: We assessed the bias introduced by viral enrichment on mock assemblages composed of seven DNA viruses, and the bias from random amplification methods on human saliva DNA viromes, using qPCR and deep sequencing, respectively. While iodixanol cushions and 0.45 μm filtration preserved the original composition of nuclease-protected viral genomes, low-force centrifugation and 0.22 μm filtration removed large viruses. Comparison of unamplified and randomly amplified saliva viromes revealed that multiple displacement amplification (MDA) induced stochastic bias from picograms of DNA template. However, the type of bias shifted to systematic using 1 ng, with only a marginal influence by amplification time. Systematic bias consisted of over-amplification of small circular genomes, and under-amplification of those with extreme GC content, a negative bias that was shared with the PCR-based sequence-independent, single-primer amplification (SISPA) method. MDA based on random priming provided by a DNA primase activity slightly outperformed those based on random hexamers and SISPA, which may reflect differences in ability to handle sequences with extreme GC content. SISPA viromes showed uneven coverage profiles, with high coverage peaks in regions with low linguistic sequence complexity. Despite misrepresentation of certain viruses after random amplification, ordination plots based on dissimilarities among contig profiles showed perfect overlapping of related amplified and unamplified saliva viromes and strong separation from unrelated saliva viromes. This result suggests that random amplification bias has a minor impact on beta diversity studies.

CONCLUSIONS: Benchmark analyses of mock and natural communities of viruses improve understanding and mitigate bias in metagenomics surveys. Bias induced by random amplification methods has only a minor impact on beta diversity studies of human saliva viromes.}, } @article {pmid29954451, year = {2018}, author = {Negussie, A and Debalke, D and Belachew, T and Tadesse, F}, title = {Tuberculosis co-infection and its associated factors among People living with HIV/AIDS attending antiretroviral therapy clinic in southern Ethiopia: a facility based retrospective study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {417}, pmid = {29954451}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Child ; *Coinfection ; Cross-Sectional Studies ; Ethiopia ; Female ; HIV Infections/*complications/diagnosis/drug therapy ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Tuberculosis/*complications/diagnosis/drug therapy ; Young Adult ; }, abstract = {OBJECTIVE: The study aimed to determine the prevalence and identify determinants of TB among People living with HIV/AIDS (PLWHAs) through reviewing and analyzing patient case files from the anti-retro viral treatment (ART) clinic of Yirgalem General Hospital, southern Ethiopia.

RESULTS: Of the total PLWHAs involved in the study, 51 (36.9%) of them were found to have TB, and of which, 37 (72.5%) were smear negative cases. The multivariate analysis showed that PLWHA's who are at WHO clinical stage 3 (AOR = 5.82; 95% CI 1.04-32.30), CD4 level of 200-500 cells/mm3 (AOR = 4.85; 95% CI 1.95-12.05) and < 200 cells/mm3 (AOR = 7.34; 95% CI 2.75-19.58) at ART initiation, and who didn't take INH prophylaxis (AOR = 12.36; 95% CI 4.47-34.14) were significantly associated with TB-HIV co-infection. Rapid and sensitive diagnostic techniques should be implemented to early detect co-infections, and also INH prophylactic preventive measures should be strengthened to reduce TB incidence.}, } @article {pmid29954450, year = {2018}, author = {Kebede, A and Gerensea, H}, title = {Prevalence of needle stick injury and its associated factors among nurses working in public hospitals of Dessie town, Northeast Ethiopia, 2016.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {413}, pmid = {29954450}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Hospitals, Public ; Humans ; Male ; Middle Aged ; Needlestick Injuries/*epidemiology ; Nurses/*statistics & numerical data ; Prevalence ; Young Adult ; }, abstract = {OBJECTIVE: Nurses are exposed to dangerous and deadly blood borne pathogens through contaminated needle stick injuries. This study was designed to assess prevalence of needle stick injury and its associated factors among nurses working in hospitals. Institution-based cross-sectional study design was used among 258 randomly selected nurses. Collected data was entered into Epi-Data version 3.1 and transferred to SPSS Version 20.0 for analysis. The degree of variables were assessed using adjusted odds ratio and its 95% confidence interval with P value (< 0.05).

RESULTS: Eighty-nine (34.5%) nurses self-reported receiving a needle stick injury in the previous 12 months. Work experience, working hour, personal protective, infection prevention guide line utilization and infection prevention training were significantly associated to needle stick injury.

CONCLUSIONS: The needle stick injury in this study area was prevalent. The contributing factors to the injury were duration of working hours, experience, use of personal protective equipment and training.}, } @article {pmid29954448, year = {2018}, author = {Freitas, AC and Bocking, A and Hill, JE and Money, DM and , }, title = {Increased richness and diversity of the vaginal microbiota and spontaneous preterm birth.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {117}, pmid = {29954448}, issn = {2049-2618}, support = {108030//CIHR/Canada ; MOP-82799//CIHR/Canada ; }, mesh = {Adult ; Biodiversity ; Female ; Gardnerella vaginalis/classification/genetics/*isolation & purification ; Gestational Age ; Humans ; Infant, Newborn ; Lactobacillus/classification/genetics/*isolation & purification ; Microbiota/*genetics ; Middle Aged ; Pregnancy ; Premature Birth/*microbiology ; Retrospective Studies ; Surveys and Questionnaires ; Tenericutes/classification/genetics/*isolation & purification ; Vagina/*microbiology ; Young Adult ; }, abstract = {BACKGROUND: The bacterial community present in the female lower genital tract plays an important role in maternal and neonatal health. Imbalances in this microbiota have been associated with negative reproductive outcomes, such as spontaneous preterm birth (sPTB), but the mechanisms underlying the association between a disturbed microbiota and sPTB remain poorly understood. An intrauterine infection ascending from the vagina is thought to be an important contributor to the onset of preterm labour. Our objective was to characterize the vaginal microbiota of pregnant women who had sPTB (n = 46) and compare to those of pregnant women who delivered at term (n = 170). Vaginal swabs were collected from women at 11-16 weeks of gestational age. Microbiota profiles were created by PCR amplification and pyrosequencing of the cpn60 universal target region.

RESULTS: Profiles clustered into seven community state types: I (Lactobacillus crispatus dominated), II (Lactobacillus gasseri dominated), III (Lactobacillus iners dominated), IVA (Gardnerella vaginalis subgroup B or mix of species), IVC (G. vaginalis subgroup A dominated), IVD (G. vaginalis subgroup C dominated) and V (Lactobacillus jensenii dominated). The microbiota of women who experienced preterm birth (< 37 weeks gestation) had higher richness and diversity and higher Mollicutes prevalence when compared to those of women who delivered at term. The two groups did not cluster according to CST, likely because CST assignment is driven in most cases by the dominance of one particular species, overwhelming the contributions of more rare taxa. In conclusion, we did not identify a specific microbial community structure that predicts sPTB, but differences in microbiota richness, diversity and Mollicutes prevalence were observed between groups.

CONCLUSIONS: Although a causal relationship remains to be determined, our results confirm previous reports of an association between Mollicutes and sPTB and further suggest that a more diverse microbiome may be important in the pathogenesis of some cases.}, } @article {pmid29954436, year = {2018}, author = {do Socorro Nantua Evangelista, M and Maia, R and Toledo, JP and de Abreu, RG and Braga, JU and Barreira, D and Trajman, A}, title = {Second month sputum smear as a predictor of tuberculosis treatment outcomes in Brazil.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {414}, pmid = {29954436}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antitubercular Agents/*therapeutic use ; Brazil ; Female ; Humans ; Infant, Newborn ; Male ; Middle Aged ; Mycobacterium tuberculosis ; Sputum/*microbiology ; Treatment Outcome ; Tuberculosis, Pulmonary/*drug therapy ; Young Adult ; }, abstract = {OBJECTIVE: The value of sputum smear microscopy (SSM) after 2 months of treatment in the management of pulmonary tuberculosis is controversial. We analysed second month-SSM conversion as a predictor of treatment success in Brazil.

RESULTS: Overall successful outcome rate was 89.4%. The predictive value of second month-SSM conversion for successful outcomes was 85.2% 72,479/85,118), while the predictive value of non-conversion for unfavourable outcomes was 26.9% (2712/10,071). Unfavourable treatment outcomes were twice more likely among patients who did not convert (adjusted OR = 2.06; 1.97-2.16).}, } @article {pmid29954432, year = {2018}, author = {Faust, K and Bauchinger, F and Laroche, B and de Buyl, S and Lahti, L and Washburne, AD and Gonze, D and Widder, S}, title = {Signatures of ecological processes in microbial community time series.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {120}, pmid = {29954432}, issn = {2049-2618}, mesh = {Bacterial Load/*methods ; Biodiversity ; *Computer Simulation ; Ecology ; *Ecosystem ; Ecotype ; Gastrointestinal Microbiome/*physiology ; Humans ; *Models, Biological ; *Time and Motion Studies ; }, abstract = {BACKGROUND: Growth rates, interactions between community members, stochasticity, and immigration are important drivers of microbial community dynamics. In sequencing data analysis, such as network construction and community model parameterization, we make implicit assumptions about the nature of these drivers and thereby restrict model outcome. Despite apparent risk of methodological bias, the validity of the assumptions is rarely tested, as comprehensive procedures are lacking. Here, we propose a classification scheme to determine the processes that gave rise to the observed time series and to enable better model selection.

RESULTS: We implemented a three-step classification scheme in R that first determines whether dependence between successive time steps (temporal structure) is present in the time series and then assesses with a recently developed neutrality test whether interactions between species are required for the dynamics. If the first and second tests confirm the presence of temporal structure and interactions, then parameters for interaction models are estimated. To quantify the importance of temporal structure, we compute the noise-type profile of the community, which ranges from black in case of strong dependency to white in the absence of any dependency. We applied this scheme to simulated time series generated with the Dirichlet-multinomial (DM) distribution, Hubbell's neutral model, the generalized Lotka-Volterra model and its discrete variant (the Ricker model), and a self-organized instability model, as well as to human stool microbiota time series. The noise-type profiles for all but DM data clearly indicated distinctive structures. The neutrality test correctly classified all but DM and neutral time series as non-neutral. The procedure reliably identified time series for which interaction inference was suitable. Both tests were required, as we demonstrated that all structured time series, including those generated with the neutral model, achieved a moderate to high goodness of fit to the Ricker model.

CONCLUSIONS: We present a fast and robust scheme to classify community structure and to assess the prevalence of interactions directly from microbial time series data. The procedure not only serves to determine ecological drivers of microbial dynamics, but also to guide selection of appropriate community models for prediction and follow-up analysis.}, } @article {pmid29954347, year = {2018}, author = {Guo, Q and Yang, J and Forsythe, SJ and Jiang, Y and Han, W and He, Y and Niu, B}, title = {DNA sequence-based re-assessment of archived Cronobacter sakazakii strains isolated from dairy products imported into China between 2005 and 2006.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {506}, pmid = {29954347}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; 31671936//The National Nature Foundation/ ; }, mesh = {Bacterial Proteins/genetics ; China ; Cronobacter sakazakii/classification/*genetics/isolation & purification ; DNA, Bacterial/chemistry/*isolation & purification/metabolism ; Dairy Products/*microbiology ; Food Microbiology ; Humans ; Multilocus Sequence Typing ; Peptide Elongation Factor G/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Serogroup ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Cronobacter species are associated with severe foodborne infections in neonates and infants, with particular pathovars associated with specific clinical presentations. However, before 2008 the genus was regarded as a single species named Enterobacter sakazakii which was subdivided into 8 phenotypes. This study re-analyzed, using multi-locus sequence typing (MLST) and whole genome sequence with single nucleotide polymorphism analysis (WGS-SNP), 52 strains which had been identified as Enterobacter sakazakii as according to the convention at the time of isolation. These strains had been isolated from dairy product imports into China from 9 countries between 2005 and 6. Bioinformatic analysis was then used to analyze the relatedness and global dissemination of these strains.

RESULT: FusA allele sequencing revealed that 49/52 strains were Cronobacter sakazakii, while the remaining 3 strains were Escherichia coli, Enterobacter cloacae, and Franconibacter helveticus. The C. sakazakii strains comprised of 8 sequence types (STs) which included the neonatal pathovars ST1, ST4 and ST12. The predominant sequence type was ST13 (65.3%, 32/49) which had been isolated from dairy products imported from 6 countries. WGS-SNP analysis of the 32 C. sakazakii ST13 strains revealed 5 clusters and 5 unique strains which did not correlate with the country of product origin.

CONCLUSION: The mis-identification of E. coli, E. cloacae and F. helveticus as Cronobacter spp. reinforces the need to apply reliable methods to reduce the incidence of false positive and false negative results which may be of clinical significance. The WGS-SNP analysis demonstrated that indistinguishable Cronobacter strains within a sequence type can be unrelated, and may originate from multiple sources. The use of WGS-SNP analysis to distinguishing of strains within a sequence type has important relevance for tracing the source of outbreaks due to Cronobacter spp.}, } @article {pmid29954342, year = {2018}, author = {Yang, Y and Dai, M and Huang, J and Lin, X and Yang, C and Chen, M and Liu, J}, title = {LPG: A four-group probabilistic approach to leveraging pleiotropy in genome-wide association studies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {503}, pmid = {29954342}, issn = {1471-2164}, support = {MOE2016-T2-2-029//AcRF Tier 2/ ; 22302815//Hong Kong Research Grant Council/ ; 12301417//Hong Kong Research Grant Council/ ; //Wellcome Trust/United Kingdom ; 61501389//National Science Funding of China/ ; R-913-200-098-263//Duke-NUS Medical School/ ; 12316116//Hong Kong Research Grant Council/ ; }, mesh = {Algorithms ; Arthritis, Rheumatoid/genetics ; Bayes Theorem ; Crohn Disease/genetics ; Diabetes Mellitus, Type 1/genetics ; *Genetic Pleiotropy ; Genome-Wide Association Study/*methods ; Humans ; Internet Access ; Polymorphism, Single Nucleotide ; User-Computer Interface ; }, abstract = {BACKGROUND: To date, genome-wide association studies (GWAS) have successfully identified tens of thousands of genetic variants among a variety of traits/diseases, shedding light on the genetic architecture of complex disease. The polygenicity of complex diseases is a widely accepted phenomenon through which a vast number of risk variants, each with a modest individual effect, collectively contribute to the heritability of complex diseases. This imposes a major challenge on fully characterizing the genetic bases of complex diseases. An immediate implication of polygenicity is that a much larger sample size is required to detect individual risk variants with weak/moderate effects. Meanwhile, accumulating evidence suggests that different complex diseases can share genetic risk variants, a phenomenon known as pleiotropy.

RESULTS: In this study, we propose a statistical framework for Leveraging Pleiotropic effects in large-scale GWAS data (LPG). LPG utilizes a variational Bayesian expectation-maximization (VBEM) algorithm, making it computationally efficient and scalable for genome-wide-scale analysis. To demonstrate the advantages of LPG over existing methods that do not leverage pleiotropy, we conducted extensive simulation studies and applied LPG to analyze two pairs of disorders (Crohn's disease and Type 1 diabetes, as well as rheumatoid arthritis and Type 1 diabetes). The results indicate that by levelaging pleiotropy, LPG can improve the power of prioritization of risk variants and the accuracy of risk prediction.

CONCLUSIONS: Our methodology provides a novel and efficient tool to detect pleiotropy among GWAS data for multiple traits/diseases collected from different studies. The software is available at https://github.com/Shufeyangyi2015310117/LPG .}, } @article {pmid29954338, year = {2018}, author = {Sollars, ESA and Buggs, RJA}, title = {Genome-wide epigenetic variation among ash trees differing in susceptibility to a fungal disease.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {502}, pmid = {29954338}, issn = {1471-2164}, support = {BB/L012162/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; INTERCROSSING//H2020 Marie Skłodowska-Curie Actions/ ; EP/K000128/1//Engineering and Physical Sciences Research Council/ ; }, mesh = {Ascomycota/pathogenicity ; DNA Methylation ; DNA, Plant/chemistry/isolation & purification/metabolism ; *Disease Susceptibility ; *Epigenomics ; Fraxinus/*genetics ; Gene Duplication ; Gene Silencing ; Genetic Variation ; *Genome, Plant ; Genotype ; Plant Diseases/*genetics/microbiology ; Principal Component Analysis ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: European ash trees (Fraxinus excelsior) are currently threatened by ash dieback (ADB) caused by the fungus Hymenoscyphus fraxineus but a small percentage of the population possesses natural low susceptibility. The genome of a European ash tree has recently been sequenced. Here, we present whole genome DNA methylation data for two F. excelsior genotypes with high susceptibility to ADB, and two genotypes with low susceptibility, each clonally replicated. We also include two genotypes of Manchurian ash (F. mandshurica), an ash species which has co-evolved with H. fraxineus and also has low susceptibility to ADB.

RESULTS: In F. excelsior, we find an average methylation level of 76.2% in the CG context, 52.0% in the CHG context, and 13.9% in the CHH context; similar levels to those of tomato. We find higher methylation in transposable elements as opposed to non-mobile elements, and high densities of Non-Differentially Methylation Positions (N-DMPs) in genes with housekeeping functions. Of genes putatively duplicated in whole genome duplication (WGD) events, an average of 25.9% are differentially methylated in at least one cytosine context, potentially indicative of unequal silencing. Variability in methylation patterns exists among clonal replicates, and this is only slightly less than the variability found between different genotypes. Of twenty genes previously found to have expression levels associated with ADB susceptibility, we find only two of these have differential methylation between high and low susceptibility F. excelsior trees. In addition, we identify 1683 significant Differentially Methylated Regions (DMRs) (q-value< 0.001) between the high and low susceptibility genotypes of F. excelsior trees, of which 665 remain significant when F. mandshurica samples are added to the low susceptibility group.

CONCLUSIONS: We find a higher frequency of differentially methylated WGD-derived gene duplicates in ash than other plant species previously studied. We also identify a set of genes with differential methylation between genotypes and species with high versus low susceptibility to ADB. This provides valuable foundational data for future work on the role that epigenetics may play in gene dosage compensation and susceptibility to ADB in ash.}, } @article {pmid29954335, year = {2018}, author = {Kaur, A and Capalash, N and Sharma, P}, title = {Quorum sensing in thermophiles: prevalence of autoinducer-2 system.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {62}, pmid = {29954335}, issn = {1471-2180}, abstract = {BACKGROUND: Quorum sensing is a mechanism of cell to cell communication that requires the production and detection of signaling molecules called autoinducers. Although mesophilic bacteria is known to utilize this for synchronization of physiological processes such as bioluminescence, virulence, biofilm formation, motility and cell competency through signaling molecules (acyl homoserine lactones, AI-1; oligopeptides, peptide based system and furanosyl borate diester, AI-2), the phenomenon of quorum sensing in thermophiles is largely unknown.

RESULTS: In this study, proteomes of 106 thermophilic eubacteria and 21 thermophilic archaea have been investigated for the above three major quorum sensing systems to find the existence of quorum sensing in these thermophiles as there are evidences for the formation of biofilms in hot environments. Our investigation demonstrated that AI-1 system is absent in thermophiles. Further, complete peptide based two component systems for quorum sensing was also not found in any thermophile however the traces for the presence of response regulators for peptide based system were found in some of them. BLASTp search using LuxS (AI-2 synthase) protein sequence of Escherichia coli str. K-12 substr. MG1655 and autoinducer-2 receptors (LuxP of Vibrio harveyi, LsrB of E. coli str. K-12 substr. MG1655 and RbsB of Aggregatibacter actinomycetemcomitans) as queries revealed that 17 thermophilic bacteria from phyla Deinococcus- Thermus and Firmicutes possess complete AI-2 system (LuxS and LsrB and/or RbsB). Out of 106 thermophilic eubacteria 18 from phyla Deinococcus- Thermus, Proteobacteria and Firmicutes have only LuxS that might function as AI-2 synthesizing protein whereas, 16 are having only LsrB and/or RbsB which may function as AI-2 receptor in biofilms.

CONCLUSIONS: We anticipate that thermophilic bacteria may use elements of LsrB and RbsB operon for AI-2 signal transduction and they may use quorum sensing for purposes like biofilm formation. Nevertheless, thermophiles in which no known quorum sensing system was found may use some unknown mechanisms as the mode of communication. Further information regarding quorum sensing will be explored to develop strategies to disrupt the biofilms of thermophiles.}, } @article {pmid29954330, year = {2018}, author = {Mei, S and Flemington, EK and Zhang, K}, title = {Transferring knowledge of bacterial protein interaction networks to predict pathogen targeted human genes and immune signaling pathways: a case study on M. tuberculosis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {505}, pmid = {29954330}, issn = {1471-2164}, support = {G12 MD007595/MD/NIMHD NIH HHS/United States ; P01 CA214091/CA/NCI NIH HHS/United States ; P20 GM103424/GM/NIGMS NIH HHS/United States ; R01 AI101046/AI/NIAID NIH HHS/United States ; }, mesh = {Area Under Curve ; Bacterial Proteins/*metabolism ; Databases, Genetic ; Drug Resistance, Bacterial/genetics ; Gene Ontology ; Host-Pathogen Interactions/*genetics ; Humans ; Immune System/metabolism/microbiology ; Logistic Models ; Mycobacterium tuberculosis/*metabolism ; Protein Interaction Maps/*genetics ; ROC Curve ; Signal Transduction/*genetics ; Tuberculosis/*genetics/immunology/microbiology/pathology ; }, abstract = {BACKGROUND: Bacterial invasive infection and host immune response is fundamental to the understanding of pathogen pathogenesis and the discovery of effective therapeutic drugs. However, there are very few experimental studies on the signaling cross-talks between bacteria and human host to date.

METHODS: In this work, taking M. tuberculosis H37Rv (MTB) that is co-evolving with its human host as an example, we propose a general computational framework that exploits the known bacterial pathogen protein interaction networks in STRING database to predict pathogen-host protein interactions and their signaling cross-talks. In this framework, significant interlogs are derived from the known pathogen protein interaction networks to train a predictive l2-regularized logistic regression model.

RESULTS: The computational results show that the proposed method achieves excellent performance of cross validation as well as low predicted positive rates on the less significant interlogs and non-interlogs, indicating a low risk of false discovery. We further conduct gene ontology (GO) and pathway enrichment analyses of the predicted pathogen-host protein interaction networks, which potentially provides insights into the machinery that M. tuberculosis H37Rv targets human genes and signaling pathways. In addition, we analyse the pathogen-host protein interactions related to drug resistance, inhibition of which potentially provides an alternative solution to M. tuberculosis H37Rv drug resistance.

CONCLUSIONS: The proposed machine learning framework has been verified effective for predicting bacteria-host protein interactions via known bacterial protein interaction networks. For a vast majority of bacterial pathogens that lacks experimental studies of bacteria-host protein interactions, this framework is supposed to achieve a general-purpose applicability. The predicted protein interaction networks between M. tuberculosis H37Rv and Homo sapiens, provided in the Additional files, promise to gain applications in the two fields: (1) providing an alternative solution to drug resistance; (2) revealing the patterns that M. tuberculosis H37Rv genes target human immune signaling pathways.}, } @article {pmid29954329, year = {2018}, author = {Bai, H and Sun, Y and Liu, N and Xue, F and Li, Y and Xu, S and Ye, J and Zhang, L and Chen, Y and Chen, J}, title = {Single SNP- and pathway-based genome-wide association studies for beak deformity in chickens using high-density 600K SNP arrays.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {501}, pmid = {29954329}, issn = {1471-2164}, support = {CARS-40//China Agriculture Research Systems/ ; 31501949//National Natural Science Foundation of China/ ; D171100007817005//Beijing Municipal Science and Technology Project/ ; ASTIPIAS04//Agricultural Science and Technology Innovation Program/ ; CAAS-XTCX2016010-03//Agricultural Science and Technology Innovation Program/ ; }, mesh = {Animals ; Beak/abnormalities/*metabolism ; Chickens/*genetics ; *Genome-Wide Association Study ; Genotype ; Metabolic Networks and Pathways/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Beak deformity, typically expressed as the crossing of upper and lower mandibles, is found in several indigenous chicken breeds, including the Beijing-You chickens studied here. Beak deformity severely impairs the birds' growth and welfare. Although previous studies shed some light on the genetic regulation of this complex trait, the genetic basis of this malformation remains incompletely understood.

RESULTS: In this study, single SNP- and pathway-based genome-wide association studies (GWASs) were performed using ROADTRIPS and SNP ratio test (SRT), respectively. A total of 48 birds with deformed beaks (case) and 48 normal birds (control) were genotyped using Affymetrix 600 K HD genotyping arrays. As a result, 95 individuals and 429,539 SNPs were obtained after quality control. The P-value was corrected by a Bonferroni adjustment based on linkage disequilibrium pruning. The single SNP-based association study identified one associated SNP with 5% genome-wide significance and seven suggestively associated SNPs. Four high-confidence genes, LOC421892, TDRD3, RET, and STMN1, were identified as the most promising candidate genes underlying this complex trait in view of their positions, functions, and overlaps with previous studies. The pathway-based association study highlighted the association of six pathways with beak deformity, including the calcium signaling pathway.

CONCLUSIONS: Potentially useful candidate genes and pathways for beak deformity were identified, which should be the subject of further functional characterization.}, } @article {pmid29954327, year = {2018}, author = {Liu, L and Zhu, W and Liu, J and Wang, S and Jiang, J}, title = {Identification and differential regulation of microRNAs during thyroid hormone-dependent metamorphosis in Microhyla fissipes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {507}, pmid = {29954327}, issn = {1471-2164}, support = {2015XBZG_XBQNXZ_B_011//Western Light Talent Culture Project of the Chinese Academy of Sciences/ ; KJZG-EW-L13//Important Research Project of Chinese Academy of Sciences/ ; }, mesh = {Animals ; Anura/*genetics/growth & development ; Female ; Gene Expression Regulation, Developmental/drug effects ; Intestines/pathology ; Larva/drug effects/genetics ; Male ; Metamorphosis, Biological/drug effects/*genetics ; MicroRNAs/*genetics/metabolism ; Phosphatidylinositol 3-Kinases/genetics/metabolism ; Proto-Oncogene Proteins c-akt/genetics/metabolism ; Signal Transduction/drug effects ; Thyroid Hormones/*metabolism ; Triiodothyronine/pharmacology ; }, abstract = {BACKGROUND: Anuran metamorphosis, which is obligatorily initiated and sustained by thyroid hormone (TH), is a dramatic example of extensive morphological, biochemical and cellular changes occurring during post-embryonic development. Thus, it provides an ideal model to understand the actions of the hormone and molecular mechanisms underlying these developmental and apoptotic processes. In addition to transcriptional factors, microRNAs (miRNAs) play key roles in diverse biological processes via post-transcriptional repression of mRNAs. However, the possible role of miRNAs in anuran metamorphosis is not well understood. Screening and identification of TH-responding miRNAs are required to reveal the integrated regulatory mechanisms of TH during metamorphosis. Given the specific role of TRs during M. fissipes metamorphosis and the characteristics of M. fissipes as an ideal model, Illumina sequencing technology was employed to get a full scope of miRNA in M. fissipes metamorphosis treated by T3.

RESULTS: Morphological and histological analysis revealed that 24 h T3 treatment M. fissipes tadpoles resembled that at the climax of natural metamorphosis. Thus, small RNA libraries were constructed from control and 24 h T3 treatment groups. A total of 164 conserved miRNAs and 36 predicted novel miRNAs were characterized. Furthermore, 5' first and ninth nucleotides of miRNAs were significantly enriched in U in our study. In all, 21 miRNAs were differentially expressed between the T3 and control groups (p < 0.01). A total of 10,206 unigenes were identified as target genes of these differentially expressed miRNAs. KEGG pathway analysis indicated that the most overrepresented miRNA target genes were enriched in the "PI3k-Akt signaling pathway". In addition, a network associated with the TH signaling pathway provides an opportunity to further understand the complex biological processes that occur in metamorphosis.

CONCLUSIONS: We identified a large number of miRNAs during M. fissipes metamorphosis, and 21 of them were differentially expressed in the two groups that represented two different metamorphic stages. These miRNAs may play important roles during metamorphosis. The study gives us clues for further studies of the mechanisms of anuran metamorphosis and provides a model to study the mechanism of TH-affected biological processes in humans.}, } @article {pmid29954325, year = {2018}, author = {Broustas, CG and Harken, AD and Garty, G and Amundson, SA}, title = {Identification of differentially expressed genes and pathways in mice exposed to mixed field neutron/photon radiation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {504}, pmid = {29954325}, issn = {1471-2164}, support = {P41 EB002033/EB/NIBIB NIH HHS/United States ; U19 AI067773/AI/NIAID NIH HHS/United States ; U19AI067773//National Institute of Allergy and Infectious Diseases/ ; 5P41EB-002033//National Institute of Biomedical Imaging and Bioengineering/ ; }, mesh = {Animals ; Gene Expression Regulation/radiation effects ; Gene Ontology ; Male ; Metabolic Networks and Pathways/radiation effects ; Mice ; Mice, Inbred C57BL ; *Neutrons ; Oligonucleotide Array Sequence Analysis ; Photons ; Radiation Dosage ; Signal Transduction/radiation effects ; Transcriptome/*radiation effects ; X-Rays ; }, abstract = {BACKGROUND: Radiation exposure due to the detonation of an improvised nuclear device remains a major security concern. Radiation from such a device involves a combination of photons and neutrons. Although photons will make the greater contribution to the total dose, neutrons will certainly have an impact on the severity of the exposure as they have high relative biological effectiveness.

RESULTS: We investigated the gene expression signatures in the blood of mice exposed to 3 Gy x-rays, 0.75 Gy of neutrons, or to mixed field photon/neutron with the neutron fraction contributing 5, 15%, or 25% of a total 3 Gy radiation dose. Gene ontology and pathway analysis revealed that genes involved in protein ubiquitination pathways were significantly overrepresented in all radiation doses and qualities. On the other hand, eukaryotic initiation factor 2 (EIF2) signaling pathway was identified as one of the top 10 ranked canonical pathways in neutron, but not pure x-ray, exposures. In addition, the related mTOR and regulation of EIF4/p70S6K pathways were also significantly underrepresented in the exposures with a neutron component, but not in x-ray radiation. The majority of the changed genes in these pathways belonged to the ribosome biogenesis and translation machinery and included several translation initiation factors (e.g. Eif2ak4, Eif3f), as well as 40S and 60S ribosomal subunits (e.g. Rsp19, Rpl19, Rpl27). Many of the differentially downregulated ribosomal genes (e.g. RPS19, RPS28) have been causally associated with human bone marrow failure syndromes and hematologic malignancies. We also observed downregulation of transfer RNA processes, in the neutron-only exposure (p < 0.005). Ingenuity Pathway Analysis (p < 0.05) of differentially expressed genes predicted significantly suppressed activity of the upstream regulators c-Myc and Mycn, transcription factors known to control ribosome biogenesis.

CONCLUSIONS: We describe the gene expression profile of mouse blood following exposure to mixed field neutron/photon irradiation. We have discovered that pathways related to protein translation are significantly underrepresented in the exposures containing a neutron component. Our results highlight the significance of neutron exposures that even the smallest percentage can have profound biological effects that will affect medical management and treatment decisions in case of a radiological emergency.}, } @article {pmid29954319, year = {2018}, author = {Sheehan, G and Clarke, G and Kavanagh, K}, title = {Characterisation of the cellular and proteomic response of Galleria mellonella larvae to the development of invasive aspergillosis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {63}, pmid = {29954319}, issn = {1471-2180}, abstract = {BACKGROUND: Galleria mellonella larvae were infected with conidia of Aspergillus fumigatus and the cellular and humoral immune responses of larvae to the pathogen were characterized as invasive aspergillosis developed.

RESULTS: At 2 h post-infection there was an increase in hemocyte density to 7.43 ± 0.50 × 106/ml from 0.98 ± 0.08 × 106/ml at 0 h. Hemocytes from larvae immune primed for 6 h with heat killed A. fumigatus conidia displayed superior anti-fungal activity. Examination of the spread of the fungus by Cryo-imaging and fluorescent microscopy revealed dissemination of the fungus through the larvae by 6 h and the formation of distinct nodules in tissue. By 24 h a range of nodules were visible at the site of infection and at sites distant from that indicating invasion of tissue. Proteomic analysis of larvae infected with viable conidia for 6 h demonstrated an increase in the abundance of gustatory receptor candidate 25 (37 fold), gloverin-like protein (14 fold), cecropin-A (11 fold). At 24 h post-infection gustatory receptor candidate 25 (126 fold), moricin-like peptide D (33 fold) and muscle protein 20-like protein (12 fold) were increased in abundance. Proteins decreased in abundance included fibrohexamerin (13 fold) and dimeric dihydrodiol dehydrogenase (8 fold).

CONCLUSION: The results presented here indicate that G. mellonella larvae may be a convenient model for studying the stages in the development of invasive aspergillosis and may offer an insight into this process in mammals.}, } @article {pmid29954318, year = {2018}, author = {Bachman, JA and Gyori, BM and Sorger, PK}, title = {FamPlex: a resource for entity recognition and relationship resolution of human protein families and complexes in biomedical text mining.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {248}, pmid = {29954318}, issn = {1471-2105}, abstract = {BACKGROUND: For automated reading of scientific publications to extract useful information about molecular mechanisms it is critical that genes, proteins and other entities be correctly associated with uniform identifiers, a process known as named entity linking or "grounding." Correct grounding is essential for resolving relationships among mined information, curated interaction databases, and biological datasets. The accuracy of this process is largely dependent on the availability of machine-readable resources associating synonyms and abbreviations commonly found in biomedical literature with uniform identifiers.

RESULTS: In a task involving automated reading of ∼215,000 articles using the REACH event extraction software we found that grounding was disproportionately inaccurate for multi-protein families (e.g., "AKT") and complexes with multiple subunits (e.g."NF- κB"). To address this problem we constructed FamPlex, a manually curated resource defining protein families and complexes as they are commonly encountered in biomedical text. In FamPlex the gene-level constituents of families and complexes are defined in a flexible format allowing for multi-level, hierarchical membership. To create FamPlex, text strings corresponding to entities were identified empirically from literature and linked manually to uniform identifiers; these identifiers were also mapped to equivalent entries in multiple related databases. FamPlex also includes curated prefix and suffix patterns that improve named entity recognition and event extraction. Evaluation of REACH extractions on a test corpus of ∼54,000 articles showed that FamPlex significantly increased grounding accuracy for families and complexes (from 15 to 71%). The hierarchical organization of entities in FamPlex also made it possible to integrate otherwise unconnected mechanistic information across families, subfamilies, and individual proteins. Applications of FamPlex to the TRIPS/DRUM reading system and the Biocreative VI Bioentity Normalization Task dataset demonstrated the utility of FamPlex in other settings.

CONCLUSION: FamPlex is an effective resource for improving named entity recognition, grounding, and relationship resolution in automated reading of biomedical text. The content in FamPlex is available in both tabular and Open Biomedical Ontology formats at https://github.com/sorgerlab/famplex under the Creative Commons CC0 license and has been integrated into the TRIPS/DRUM and REACH reading systems.}, } @article {pmid29954317, year = {2018}, author = {Wang, H and He, L and Liu, B and Feng, Y and Zhou, H and Zhang, Z and Wu, Y and Wang, J and Gan, Y and Yuan, T and Wu, M and Xie, X and Feng, Z}, title = {Establishment and comparison of air-liquid interface culture systems for primary and immortalized swine tracheal epithelial cells.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {10}, pmid = {29954317}, issn = {1471-2121}, support = {31700157//National Natural Science Foundation of China/International ; BK20160583//Jiangsu Province Natural Sciences Foundation/International ; }, mesh = {Animals ; Cell Culture Techniques/*methods ; Cell Line, Transformed ; Cytokines/metabolism ; Electric Impedance ; Epithelial Cells/*cytology/ultrastructure ; Female ; Inflammation Mediators/metabolism ; Mucins/metabolism ; Sus scrofa ; Tight Junctions/metabolism ; Toll-Like Receptors/agonists/metabolism ; Trachea/*cytology ; Zonula Occludens-1 Protein/metabolism ; }, abstract = {BACKGROUND: Air-liquid interface (Ali) systems allow the establishment of a culture environment more representative of that in vivo than other culture systems. They are useful for performing mechanistic studies of respiratory epithelial cells as drug permeation barriers and can be used to study the interactions between hosts and respiratory pathogens. However, there have been few studies concerning Ali cultures of primary swine tracheal epithelial cells (STECs) and an immortalized STEC line, and the differences between these two systems remain poorly defined.

RESULTS: In this study, we established Ali culture systems for primary STECs and for immortalized STEC line, and we systematically compared the differentiation capacities and immunological functions of these systems for the first time. Under Ali culture conditions, immortalized STEC line and primary STECs could survive for at least forty days, formed tight junctions and differentiated into stratified cells. They both possessed complete abilities to produce mucin and inflammatory cytokines and develop cilia. However, in contrast to primary STECs, which had a heterogeneous morphology, Ali-cultured immortalized STEC line appeared to be a homogenous population. The formation of tight junctions in Ali-cultured primary STECs was superior to that in immortalized STEC line. In addition, cilia in Ali-cultured immortalized STEC line were more pronounced, but their duration of expression was shorter than in primary STECs.

CONCLUSIONS: Ali-cultured primary STECs and immortalized STEC line systems possessing complete abilities to undergo ciliary differentiation and inflammatory cytokine production were established for the first time in this study, and several differences in morphology and the formation of tight junctions and cilia were observed between these two systems. These two systems will be important tools for drug screening studies, as well as for detailed analyses of the interactions between hosts and respiratory pathogens.}, } @article {pmid29954316, year = {2018}, author = {Iuchi, H and Sugimoto, M and Tomita, M}, title = {MICOP: Maximal information coefficient-based oscillation prediction to detect biological rhythms in proteomics data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {249}, pmid = {29954316}, issn = {1471-2105}, abstract = {BACKGROUND: Circadian rhythms comprise oscillating molecular interactions, the disruption of the homeostasis of which would cause various disorders. To understand this phenomenon systematically, an accurate technique to identify oscillating molecules among omics datasets must be developed; however, this is still impeded by many difficulties, such as experimental noise and attenuated amplitude.

RESULTS: To address these issues, we developed a new algorithm named Maximal Information Coefficient-based Oscillation Prediction (MICOP), a sine curve-matching method. The performance of MICOP in labeling oscillation or non-oscillation was compared with four reported methods using Mathews correlation coefficient (MCC) values. The numerical experiments were performed with time-series data with (1) mimicking of molecular oscillation decay, (2) high noise and low sampling frequency and (3) one-cycle data. The first experiment revealed that MICOP could accurately identify the rhythmicity of decaying molecular oscillation (MCC > 0.7). The second experiment revealed that MICOP was robust against high-level noise (MCC > 0.8) even upon the use of low-sampling-frequency data. The third experiment revealed that MICOP could accurately identify the rhythmicity of noisy one-cycle data (MCC > 0.8). As an application, we utilized MICOP to analyze time-series proteome data of mouse liver. MICOP identified that novel oscillating candidates numbered 14 and 30 for C57BL/6 and C57BL/6 J, respectively.

CONCLUSIONS: In this paper, we presented MICOP, which is an MIC-based algorithm, for predicting periodic patterns in large-scale time-resolved protein expression profiles. The performance test using artificially generated simulation data revealed that the performance of MICOP for decaying data was superior to that of the existing widely used methods. It can reveal novel findings from time-series data and may contribute to biologically significant results. This study suggests that MICOP is an ideal approach for detecting and characterizing oscillations in time-resolved omics data sets.}, } @article {pmid29953938, year = {2018}, author = {Zea, DJ and Monzon, AM and Parisi, G and Marino-Buslje, C}, title = {How is structural divergence related to evolutionary information?.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {859-866}, doi = {10.1016/j.ympev.2018.06.033}, pmid = {29953938}, issn = {1095-9513}, abstract = {The analysis of evolutionary information in a protein family, such as conservation and covariation, is often linked to its structural information. Multiple sequence alignments of distant homologous sequences are used to measure evolutionary variables. Although high structural differences between proteins can be expected in such divergent alignments, most works linking evolutionary and structural information use a single structure ignoring the structural variability within protein families. The goal of this work is to elucidate the relevance of structural divergence when sequence-based measures are integrated with structural information. We found that inter-residue contacts and solvent accessibility undergo large variations in protein families. Our results show that high covariation scores tend to reveal residue contacts that are conserved in the family, instead of protein or conformer specific contacts. We also found that residue accessible surface area shows a high variability between structures of the same family. As a consequence, the mean relative solvent accessibility of multiple structures correlates better with the conservation pattern than the relative solvent accessibility of a single structure. We conclude that the use of comprehensive structural information allows a more accurate interpretation of the information computed from sequence alignments. Therefore, considering structural divergence would lead to a better understanding of protein function, dynamics, and evolution.}, } @article {pmid29953937, year = {2018}, author = {Shelley, JJ and Swearer, SE and Adams, M and Dempster, T and Le Feuvre, MC and Hammer, MP and Unmack, PJ}, title = {Cryptic biodiversity in the freshwater fishes of the Kimberley endemism hotspot, northwestern Australia.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {843-858}, doi = {10.1016/j.ympev.2018.06.032}, pmid = {29953937}, issn = {1095-9513}, abstract = {The prevalence of unrecognised cryptic species impairs biodiversity estimates, clouds biological research and hinders conservation planning. As the rate of cryptic species detection increases globally, research is needed to determine how frequent cryptic species are, whether they are more common in given management regions, and whether these patterns are consistent across taxonomic groups. The Kimberley region in remote northwestern Australia harbours some of the most speciose, and morphologically and functionally diverse, endemic animal and plant communities on the continent. The rugged and changeable landscape also appears to contain a large proportion of cryptic terrestrial species, raising the question of whether similar patterns are also found among aquatic taxa, which have yet to be studied using integrative systematic approaches. If true, then the actual levels of aquatic biodiversity are yet to be fully realised. Here we conducted a molecular assessment of where species boundaries may exist in the Kimberley regions' most speciose freshwater fish family, the Terapontidae (grunters), with a combined morphological assessment of the regions' most speciose terapontid genus, Syncomistes. Assessment of nuclear markers (54 allozyme loci), sequence data (mitochondrial cytochrome b (cytb); nuclear recombination activation gene one (RAG1)) and 31 meristic and 36 morphometric characters provides evidence for 13 new candidate species across three different genera. Many of these candidate species are narrow range endemics. Our findings raise several questions about the evolutionary origin of the Kimberley's endemic fish fauna and highlight the likelihood that freshwater fish species diversity in the Kimberley is severely under-represented by current systematic frameworks, with significant implications for ecological research, conservation and management.}, } @article {pmid29953879, year = {2018}, author = {Cheng, X and Li, K and Liu, M and Xu, M and Hu, X and Yan, R and Förster, E and Zhao, S}, title = {The effect of P85 on neuronal proliferation and differentiation during development of mouse cerebral cortex.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {95-103}, doi = {10.1016/j.ydbio.2018.06.016}, pmid = {29953879}, issn = {1095-564X}, mesh = {Animals ; Cell Cycle/*physiology ; Cell Differentiation/*physiology ; Cerebral Cortex/cytology/*embryology ; Mice ; Neural Stem Cells/cytology/*metabolism ; Neurogenesis/*physiology ; Phosphatidylinositol 3-Kinases/genetics/*metabolism ; Signal Transduction/*physiology ; }, abstract = {Proliferation of neural stem cells and differentiation of newly generated cells are crucial steps during the development of mammalian neocortex, which are able to generate suitable number of neurons and glial cells to ensure normal formation of cortex. Any disturbance in these processes leads to structural and functional abnormalities of cerebral cortex, such as epilepsy or intellectual disability. Numerous molecules involved in the development of disorders of the nervous system have been discovered in the recent years. The PI3K/AKT signaling pathway has been shown to be widely involved in the corticogenesis. Recently we could show that overexpression of regulatory subunit P85 of PI3K disrupts neuronal migration. However, it remains unclear whether the regulatory subunit P85 plays a role in the proliferation of neural stem cells and differentiation of newly generated cells during mouse brain development. Here, by using in utero electroporation and immunohistochemistry, we show that overexpression of P85 inhibited proliferation of neural progenitor cells and neuronal differentiation. By using 5-bromo-2-deoxyuridine (BrdU) labeling, we reveal that overexpression of P85 extended the cell cycle duration, which may result in developmental retardation during mouse corticogenesis.}, } @article {pmid29952746, year = {2018}, author = {Dahal, RH and Chaudhary, DK and Kim, J}, title = {Rhodanobacter hydrolyticus sp. nov., a novel DNA- and tyrosine-hydrolysing gammaproteobacterium isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2580-2586}, doi = {10.1099/ijsem.0.002881}, pmid = {29952746}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Tyrosine/metabolism ; Xanthomonadaceae/*classification/growth & development/isolation & purification ; }, abstract = {A bacterial isolate, designated G-5-5T, was isolated from forest soil at Kyonggi University. Strain G-5-5T was acid-tolerant and alkali-tolerant. Cells were strictly aerobic, Gram-stain-negative, catalase- and oxidase-positive, non-motile, non-spore-forming, rod-shaped, and yellow-coloured. Strain G-5-5T hydrolysed DNA and tyrosine; assimilated d-glucose, maltose, N-acetyl-glucosamine and l-fucose; and tolerated only 0.5 % NaCl (w/v). Phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain G-5-5T formed a lineage within the family Rhodanobacteraceae and that it grouped with but was distinct from various members of the genus Rhodanobacter. The closest member was Rhodanobacter umsongensis GR24-2T (97.8 % sequence similarity). The sole respiratory quinone was Q-8. The major polar lipids of strain G-5-5T were phosphatidylethanolamine, phosphatidyl-N-methylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The major cellular fatty acids were summed feature 9 (iso-C17 : 1ω9c and/or C16 : 0 10-methyl), iso-C15 : 0, iso-C17 : 0, iso-C16 : 0 and anteiso-C15 : 0. The DNA G+C content of strain G-5-5T was 64.1 mol%. DNA-DNA hybridization relatedness between strain G-5-5T and other close members of the genus Rhodanobacter ranged from 19 % to 45 %. On the basis of the polyphasic characterization and phylogenetic analyses, strain G-5-5T represents a novel species of the genus Rhodanobacter, for which the name Rhodanobacter hydrolyticus sp. nov. is proposed. The type strain is G-5-5T (=KEMB 9005-533T=KACC 19113T=NBRC 112685T).}, } @article {pmid29950730, year = {2018}, author = {Anacker, C and Luna, VM and Stevens, GS and Millette, A and Shores, R and Jimenez, JC and Chen, B and Hen, R}, title = {Hippocampal neurogenesis confers stress resilience by inhibiting the ventral dentate gyrus.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {98-102}, pmid = {29950730}, issn = {1476-4687}, support = {R01 MH068542/MH/NIMH NIH HHS/United States ; R01 MH083862/MH/NIMH NIH HHS/United States ; K01 AG054765/AG/NIA NIH HHS/United States ; R01 AG043688/AG/NIA NIH HHS/United States ; R01 NS081203/NS/NINDS NIH HHS/United States ; K99 MH108719/MH/NIMH NIH HHS/United States ; R37 MH068542/MH/NIMH NIH HHS/United States ; }, mesh = {Affect ; Animals ; Calcium/analysis ; Chronic Disease ; Dentate Gyrus/*cytology/*physiology ; Male ; Mice ; Neurogenesis/*physiology ; *Resilience, Psychological ; Stress, Psychological ; }, abstract = {Adult neurogenesis in the dentate gyrus of the hippocampus is highly regulated by environmental influences, and functionally implicated in behavioural responses to stress and antidepressants1-4. However, how adult-born neurons regulate dentate gyrus information processing to protect from stress-induced anxiety-like behaviour is unknown. Here we show in mice that neurogenesis confers resilience to chronic stress by inhibiting the activity of mature granule cells in the ventral dentate gyrus (vDG), a subregion that is implicated in mood regulation. We found that chemogenetic inhibition of adult-born neurons in the vDG promotes susceptibility to social defeat stress, whereas increasing neurogenesis confers resilience to chronic stress. By using in vivo calcium imaging to record neuronal activity from large cell populations in the vDG, we show that increased neurogenesis results in a decrease in the activity of stress-responsive cells that are active preferentially during attacks or while mice explore anxiogenic environments. These effects on dentate gyrus activity are necessary and sufficient for stress resilience, as direct silencing of the vDG confers resilience whereas excitation promotes susceptibility. Our results suggest that the activity of the vDG may be a key factor in determining individual levels of vulnerability to stress and related psychiatric disorders.}, } @article {pmid29950729, year = {2018}, author = {Intlekofer, AM and Shih, AH and Wang, B and Nazir, A and Rustenburg, AS and Albanese, SK and Patel, M and Famulare, C and Correa, FM and Takemoto, N and Durani, V and Liu, H and Taylor, J and Farnoud, N and Papaemmanuil, E and Cross, JR and Tallman, MS and Arcila, ME and Roshal, M and Petsko, GA and Wu, B and Choe, S and Konteatis, ZD and Biller, SA and Chodera, JD and Thompson, CB and Levine, RL and Stein, EM}, title = {Acquired resistance to IDH inhibition through trans or cis dimer-interface mutations.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {125-129}, pmid = {29950729}, issn = {1476-4687}, support = {U54 OD020355/OD/NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R35 CA197594/CA/NCI NIH HHS/United States ; R01 CA168802/CA/NCI NIH HHS/United States ; K08 CA181507/CA/NCI NIH HHS/United States ; K08 CA201483/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; Allosteric Site/drug effects/genetics ; Aminopyridines/chemistry/*pharmacology/therapeutic use ; Animals ; Clinical Trials, Phase I as Topic ; Clinical Trials, Phase II as Topic ; Disease Progression ; Drug Resistance, Neoplasm/drug effects/*genetics ; Enzyme Inhibitors/chemistry/pharmacology/therapeutic use ; Female ; Glutamine/genetics ; Glutarates/blood/metabolism ; HEK293 Cells ; Humans ; Isocitrate Dehydrogenase/*antagonists & inhibitors/*genetics ; Isoleucine/genetics ; Leukemia, Myeloid, Acute/blood/drug therapy/*genetics ; Mice ; Mice, Inbred C57BL ; Models, Molecular ; Mutant Proteins/antagonists & inhibitors/*genetics ; *Mutation ; Protein Multimerization/*genetics ; Triazines/chemistry/*pharmacology/therapeutic use ; }, abstract = {Somatic mutations in the isocitrate dehydrogenase 2 gene (IDH2) contribute to the pathogenesis of acute myeloid leukaemia (AML) through the production of the oncometabolite 2-hydroxyglutarate (2HG)1-8. Enasidenib (AG-221) is an allosteric inhibitor that binds to the IDH2 dimer interface and blocks the production of 2HG by IDH2 mutants9,10. In a phase I/II clinical trial, enasidenib inhibited the production of 2HG and induced clinical responses in relapsed or refractory IDH2-mutant AML11. Here we describe two patients with IDH2-mutant AML who had a clinical response to enasidenib followed by clinical resistance, disease progression, and a recurrent increase in circulating levels of 2HG. We show that therapeutic resistance is associated with the emergence of second-site IDH2 mutations in trans, such that the resistance mutations occurred in the IDH2 allele without the neomorphic R140Q mutation. The in trans mutations occurred at glutamine 316 (Q316E) and isoleucine 319 (I319M), which are at the interface where enasidenib binds to the IDH2 dimer. The expression of either of these mutant disease alleles alone did not induce the production of 2HG; however, the expression of the Q316E or I319M mutation together with the R140Q mutation in trans allowed 2HG production that was resistant to inhibition by enasidenib. Biochemical studies predicted that resistance to allosteric IDH inhibitors could also occur via IDH dimer-interface mutations in cis, which was confirmed in a patient with acquired resistance to the IDH1 inhibitor ivosidenib (AG-120). Our observations uncover a mechanism of acquired resistance to a targeted therapy and underscore the importance of 2HG production in the pathogenesis of IDH-mutant malignancies.}, } @article {pmid29950728, year = {2018}, author = {Guenther, UP and Weinberg, DE and Zubradt, MM and Tedeschi, FA and Stawicki, BN and Zagore, LL and Brar, GA and Licatalosi, DD and Bartel, DP and Weissman, JS and Jankowsky, E}, title = {The helicase Ded1p controls use of near-cognate translation initiation codons in 5' UTRs.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {130-134}, pmid = {29950728}, issn = {1476-4687}, support = {R01 GM107331/GM/NIGMS NIH HHS/United States ; R35 GM118088/GM/NIGMS NIH HHS/United States ; R35 GM118135/GM/NIGMS NIH HHS/United States ; T32 GM008056/GM/NIGMS NIH HHS/United States ; }, mesh = {5' Untranslated Regions/*genetics ; Codon, Initiator/*genetics ; Cross-Linking Reagents/chemistry ; DEAD-box RNA Helicases/*metabolism ; Peptide Chain Initiation, Translational/*genetics ; Ribosome Subunits, Small, Eukaryotic/chemistry/metabolism ; Saccharomyces cerevisiae/*enzymology/*genetics ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {The conserved and essential DEAD-box RNA helicase Ded1p from yeast and its mammalian orthologue DDX3 are critical for the initiation of translation1. Mutations in DDX3 are linked to tumorigenesis2-4 and intellectual disability5, and the enzyme is targeted by a range of viruses6. How Ded1p and its orthologues engage RNAs during the initiation of translation is unknown. Here we show, by integrating transcriptome-wide analyses of translation, RNA structure and Ded1p-RNA binding, that the effects of Ded1p on the initiation of translation are connected to near-cognate initiation codons in 5' untranslated regions. Ded1p associates with the translation pre-initiation complex at the mRNA entry channel and repressing the activity of Ded1p leads to the accumulation of RNA structure in 5' untranslated regions, the initiation of translation from near-cognate start codons immediately upstream of these structures and decreased protein synthesis from the corresponding main open reading frames. The data reveal a program for the regulation of translation that links Ded1p, the activation of near-cognate start codons and mRNA structure. This program has a role in meiosis, in which a marked decrease in the levels of Ded1p is accompanied by the activation of the alternative translation initiation sites that are seen when the activity of Ded1p is repressed. Our observations indicate that Ded1p affects translation initiation by controlling the use of near-cognate initiation codons that are proximal to mRNA structure in 5' untranslated regions.}, } @article {pmid29950727, year = {2018}, author = {Calcinotto, A and Spataro, C and Zagato, E and Di Mitri, D and Gil, V and Crespo, M and De Bernardis, G and Losa, M and Mirenda, M and Pasquini, E and Rinaldi, A and Sumanasuriya, S and Lambros, MB and Neeb, A and Lucianò, R and Bravi, CA and Nava-Rodrigues, D and Dolling, D and Prayer-Galetti, T and Ferreira, A and Briganti, A and Esposito, A and Barry, S and Yuan, W and Sharp, A and de Bono, J and Alimonti, A}, title = {IL-23 secreted by myeloid cells drives castration-resistant prostate cancer.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {363-369}, doi = {10.1038/s41586-018-0266-0}, pmid = {29950727}, issn = {1476-4687}, abstract = {Patients with prostate cancer frequently show resistance to androgen-deprivation therapy, a condition known as castration-resistant prostate cancer (CRPC). Acquiring a better understanding of the mechanisms that control the development of CRPC remains an unmet clinical need. The well-established dependency of cancer cells on the tumour microenvironment indicates that the microenvironment might control the emergence of CRPC. Here we identify IL-23 produced by myeloid-derived suppressor cells (MDSCs) as a driver of CRPC in mice and patients with CRPC. Mechanistically, IL-23 secreted by MDSCs can activate the androgen receptor pathway in prostate tumour cells, promoting cell survival and proliferation in androgen-deprived conditions. Intra-tumour MDSC infiltration and IL-23 concentration are increased in blood and tumour samples from patients with CRPC. Antibody-mediated inactivation of IL-23 restored sensitivity to androgen-deprivation therapy in mice. Taken together, these results reveal that MDSCs promote CRPC by acting in a non-cell autonomous manner. Treatments that block IL-23 can oppose MDSC-mediated resistance to castration in prostate cancer and synergize with standard therapies.}, } @article {pmid29950726, year = {2018}, author = {Maya-Mendoza, A and Moudry, P and Merchut-Maya, JM and Lee, M and Strauss, R and Bartek, J}, title = {High speed of fork progression induces DNA replication stress and genomic instability.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {279-284}, doi = {10.1038/s41586-018-0261-5}, pmid = {29950726}, issn = {1476-4687}, mesh = {Cell Line, Tumor ; *Chromosome Structures/drug effects ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; *DNA Damage/drug effects ; DNA Replication/drug effects/*physiology ; *Genomic Instability/drug effects ; Humans ; Phthalazines/pharmacology ; Piperazines/pharmacology ; Poly (ADP-Ribose) Polymerase-1/antagonists & inhibitors/*metabolism ; Poly(ADP-ribose) Polymerase Inhibitors/pharmacology ; Time Factors ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Accurate replication of DNA requires stringent regulation to ensure genome integrity. In human cells, thousands of origins of replication are coordinately activated during S phase, and the velocity of replication forks is adjusted to fully replicate DNA in pace with the cell cycle1. Replication stress induces fork stalling and fuels genome instability2. The mechanistic basis of replication stress remains poorly understood despite its emerging role in promoting cancer2. Here we show that inhibition of poly(ADP-ribose) polymerase (PARP) increases the speed of fork elongation and does not cause fork stalling, which is in contrast to the accepted model in which inhibitors of PARP induce fork stalling and collapse3. Aberrant acceleration of fork progression by 40% above the normal velocity leads to DNA damage. Depletion of the treslin or MTBP proteins, which are involved in origin firing, also increases fork speed above the tolerated threshold, and induces the DNA damage response pathway. Mechanistically, we show that poly(ADP-ribosyl)ation (PARylation) and the PCNA interactor p21Cip1 (p21) are crucial modulators of fork progression. PARylation and p21 act as suppressors of fork speed in a coordinated regulatory network that is orchestrated by the PARP1 and p53 proteins. Moreover, at the fork level, PARylation acts as a sensor of replication stress. During PARP inhibition, DNA lesions that induce fork arrest and are normally resolved or repaired remain unrecognized by the replication machinery. Conceptually, our results show that accelerated replication fork progression represents a general mechanism that triggers replication stress and the DNA damage response. Our findings contribute to a better understanding of the mechanism of fork speed control, with implications for genomic (in)stability and rational cancer treatment.}, } @article {pmid29950725, year = {2018}, author = {Zhu, S and Noviello, CM and Teng, J and Walsh, RM and Kim, JJ and Hibbs, RE}, title = {Structure of a human synaptic GABAA receptor.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {67-72}, pmid = {29950725}, issn = {1476-4687}, support = {R01 DA042072/DA/NIDA NIH HHS/United States ; R01 NS095899/NS/NINDS NIH HHS/United States ; R21 DA037492/DA/NIDA NIH HHS/United States ; R33 DA037492/DA/NIDA NIH HHS/United States ; T32 GM008203/GM/NIGMS NIH HHS/United States ; }, mesh = {Benzodiazepines/antagonists & inhibitors/chemistry/metabolism/pharmacology ; Bicuculline/pharmacology ; Binding, Competitive/drug effects ; Brain Chemistry ; Cell Membrane/chemistry/metabolism ; *Cryoelectron Microscopy ; Flumazenil/chemistry/metabolism/pharmacology ; GABA Modulators/chemistry/metabolism/pharmacology ; Glycosylation ; HEK293 Cells ; Humans ; Immunoglobulin Fab Fragments/chemistry/immunology ; Ligands ; Models, Molecular ; Receptors, GABA-A/*chemistry/immunology/metabolism/*ultrastructure ; gamma-Aminobutyric Acid/chemistry/metabolism/pharmacology ; }, abstract = {Fast inhibitory neurotransmission in the brain is principally mediated by the neurotransmitter GABA (γ-aminobutyric acid) and its synaptic target, the type A GABA receptor (GABAA receptor). Dysfunction of this receptor results in neurological disorders and mental illnesses including epilepsy, anxiety and insomnia. The GABAA receptor is also a prolific target for therapeutic, illicit and recreational drugs, including benzodiazepines, barbiturates, anaesthetics and ethanol. Here we present high-resolution cryo-electron microscopy structures of the human α1β2γ2 GABAA receptor, the predominant isoform in the adult brain, in complex with GABA and the benzodiazepine site antagonist flumazenil, the first-line clinical treatment for benzodiazepine overdose. The receptor architecture reveals unique heteromeric interactions for this important class of inhibitory neurotransmitter receptor. This work provides a template for understanding receptor modulation by GABA and benzodiazepines, and will assist rational approaches to therapeutic targeting of this receptor for neurological disorders and mental illness.}, } @article {pmid29950724, year = {2018}, author = {Nusse, YM and Savage, AK and Marangoni, P and Rosendahl-Huber, AKM and Landman, TA and de Sauvage, FJ and Locksley, RM and Klein, OD}, title = {Parasitic helminths induce fetal-like reversion in the intestinal stem cell niche.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {109-113}, pmid = {29950724}, issn = {1476-4687}, support = {P01 HL107202/HL/NHLBI NIH HHS/United States ; U01 DK103147/DK/NIDDK NIH HHS/United States ; R01 AI026918/AI/NIAID NIH HHS/United States ; R37 AI026918/AI/NIAID NIH HHS/United States ; R01 AI030663/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigens, Ly/biosynthesis ; Epithelial Cells/cytology ; Female ; Fetus/*cytology/metabolism ; Helminths/*physiology ; Interferon-gamma/immunology ; Intestines/*cytology ; Male ; Membrane Proteins/biosynthesis ; Mice ; Mice, Inbred C57BL ; Nematospiroides dubius/physiology ; Parasites/*physiology ; Receptors, G-Protein-Coupled/metabolism ; *Stem Cell Niche ; Stem Cells/*cytology ; Strongylida Infections/parasitology ; }, abstract = {Epithelial surfaces form critical barriers to the outside world and are continuously renewed by adult stem cells1. Whereas dynamics of epithelial stem cells during homeostasis are increasingly well understood, how stem cells are redirected from a tissue-maintenance program to initiate repair after injury remains unclear. Here we examined infection by Heligmosomoides polygyrus, a co-evolved pathosymbiont of mice, to assess the epithelial response to disruption of the mucosal barrier. H. polygyrus disrupts tissue integrity by penetrating the duodenal mucosa, where it develops while surrounded by a multicellular granulomatous infiltrate2. Crypts overlying larvae-associated granulomas did not express intestinal stem cell markers, including Lgr53, in spite of continued epithelial proliferation. Granuloma-associated Lgr5- crypt epithelium activated an interferon-gamma (IFN-γ)-dependent transcriptional program, highlighted by Sca-1 expression, and IFN-γ-producing immune cells were found in granulomas. A similar epithelial response accompanied systemic activation of immune cells, intestinal irradiation, or ablation of Lgr5+ intestinal stem cells. When cultured in vitro, granuloma-associated crypt cells formed spheroids similar to those formed by fetal epithelium, and a sub-population of H. polygyrus-induced cells activated a fetal-like transcriptional program, demonstrating that adult intestinal tissues can repurpose aspects of fetal development. Therefore, re-initiation of the developmental program represents a fundamental mechanism by which the intestinal crypt can remodel itself to sustain function after injury.}, } @article {pmid29950723, year = {2018}, author = {Zhang, Y and Kim, MS and Jia, B and Yan, J and Zuniga-Hertz, JP and Han, C and Cai, D}, title = {Author Correction: Hypothalamic stem cells control ageing speed partly through exosomal miRNAs.}, journal = {Nature}, volume = {560}, number = {7719}, pages = {E33}, doi = {10.1038/s41586-018-0303-z}, pmid = {29950723}, issn = {1476-4687}, abstract = {The microarray data generated and analysed in this Article have been uploaded to the Gene Expression Omnibus (GEO) under accession number GSE113383 . Accordingly, the 'Data availability' section of the Methods of the original Article has been rephrased online.}, } @article {pmid29950722, year = {2018}, author = {Heft-Neal, S and Burney, J and Bendavid, E and Burke, M}, title = {Robust relationship between air quality and infant mortality in Africa.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {254-258}, doi = {10.1038/s41586-018-0263-3}, pmid = {29950722}, issn = {1476-4687}, support = {U54 MD010724/MD/NIMHD NIH HHS/United States ; }, mesh = {Africa/epidemiology ; Air Pollution/adverse effects/*analysis/*statistics & numerical data ; Cause of Death/trends ; Female ; *Geographic Mapping ; Humans ; Infant ; Infant Mortality/*trends ; Male ; Maternal Age ; Particulate Matter/adverse effects/analysis/chemistry ; Respiratory Tract Infections/mortality/prevention & control ; Risk ; Viral Vaccines/therapeutic use ; }, abstract = {Poor air quality is thought to be an important mortality risk factor globally1-3, but there is little direct evidence from the developing world on how mortality risk varies with changing exposure to ambient particulate matter. Current global estimates apply exposure-response relationships that have been derived mostly from wealthy, mid-latitude countries to spatial population data4, and these estimates remain unvalidated across large portions of the globe. Here we combine household survey-based information on the location and timing of nearly 1 million births across sub-Saharan Africa with satellite-based estimates5 of exposure to ambient respirable particulate matter with an aerodynamic diameter less than 2.5 μm (PM2.5) to estimate the impact of air quality on mortality rates among infants in Africa. We find that a 10 μg m-3 increase in PM2.5 concentration is associated with a 9% (95% confidence interval, 4-14%) rise in infant mortality across the dataset. This effect has not declined over the last 15 years and does not diminish with higher levels of household wealth. Our estimates suggest that PM2.5 concentrations above minimum exposure levels were responsible for 22% (95% confidence interval, 9-35%) of infant deaths in our 30 study countries and led to 449,000 (95% confidence interval, 194,000-709,000) additional deaths of infants in 2015, an estimate that is more than three times higher than existing estimates that attribute death of infants to poor air quality for these countries2,6. Upward revision of disease-burden estimates in the studied countries in Africa alone would result in a doubling of current estimates of global deaths of infants that are associated with air pollution, and modest reductions in African PM2.5 exposures are predicted to have health benefits to infants that are larger than most known health interventions.}, } @article {pmid29950721, year = {2018}, author = {Ackerson, MR and Mysen, BO and Tailby, ND and Watson, EB}, title = {Low-temperature crystallization of granites and the implications for crustal magmatism.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {94-97}, doi = {10.1038/s41586-018-0264-2}, pmid = {29950721}, issn = {1476-4687}, abstract = {The structure and composition of granites provide clues to the nature of silicic volcanism, the formation of continents, and the rheological and thermal properties of the Earth's upper crust as far back as the Hadean eon during the nascent stages of the planet's formation1-4. The temperature of granite crystallization underpins our thinking about many of these phenomena, but evidence is emerging that this temperature may not be well constrained. The prevailing paradigm holds that granitic mineral assemblages crystallize entirely at or above about 650-700 degrees Celsius5-7. The granitoids of the Tuolumne Intrusive Suite in California tell a different story. Here we show that quartz crystals in Tuolumne samples record crystallization temperatures of 474-561 degrees Celsius. Titanium-in-quartz thermobarometry and diffusion modelling of titanium concentrations in quartz indicate that a sizeable proportion of the mineral assemblage of granitic rocks (for example, more than 80 per cent of the quartz) crystallizes about 100-200 degrees Celsius below the accepted solidus. This has widespread implications. Traditional models of magma formation require high-temperature magma bodies, but new data8,9 suggest that volcanic rocks spend most of their existence at low temperatures; because granites are the intrusive complements of volcanic rocks, our downward revision of granite crystallization temperatures supports the observations of cold magma storage. It also affects the link between volcanoes, ore deposits and granites: ore bodies are fed by the release of fluids from granites below them in the crustal column; thus, if granitic fluids are hundreds of degrees cooler than previously thought, this has implications for research on porphyry ore deposits. Geophysical interpretations of the thermal structure of the crust and the temperature of active magmatic systems will also be affected.}, } @article {pmid29950720, year = {2018}, author = {Heger, K and Wickliffe, KE and Ndoja, A and Zhang, J and Murthy, A and Dugger, DL and Maltzman, A and de Sousa E Melo, F and Hung, J and Zeng, Y and Verschueren, E and Kirkpatrick, DS and Vucic, D and Lee, WP and Roose-Girma, M and Newman, RJ and Warming, S and Hsiao, YC and Kőműves, LG and Webster, JD and Newton, K and Dixit, VM}, title = {OTULIN limits cell death and inflammation by deubiquitinating LUBAC.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {120-124}, doi = {10.1038/s41586-018-0256-2}, pmid = {29950720}, issn = {1476-4687}, mesh = {Animals ; Caspase 8/genetics/metabolism ; *Cell Death/genetics ; Deubiquitinating Enzymes/genetics/*metabolism ; Embryo Loss/genetics ; Endopeptidases/genetics/*metabolism ; Inflammation/enzymology/genetics/*metabolism ; Interferon Type I/biosynthesis ; Mice ; Mice, Inbred C57BL ; Receptor-Interacting Protein Serine-Threonine Kinases/deficiency/genetics/metabolism ; Ubiquitin/*chemistry/*metabolism ; *Ubiquitination/genetics ; Weight Loss/genetics ; }, abstract = {OTULIN (OTU deubiquitinase with linear linkage specificity) removes linear polyubiquitin from proteins that have been modified by LUBAC (linear ubiquitin chain assembly complex) and is critical for preventing auto-inflammatory disease1,2 and embryonic lethality during mouse development3. Here we show that OTULIN promotes rather than counteracts LUBAC activity by preventing its auto-ubiquitination with linear polyubiquitin. Thus, knock-in mice that express catalytically inactive OTULIN, either constitutively or selectively in endothelial cells, resembled LUBAC-deficient mice4 and died midgestation as a result of cell death mediated by TNFR1 (tumour necrosis factor receptor 1) and the kinase activity of RIPK1 (receptor-interacting protein kinase 1). Inactivation of OTULIN in adult mice also caused pro-inflammatory cell death. Accordingly, embryonic lethality and adult auto-inflammation were prevented by the combined loss of cell death mediators: caspase 8 for apoptosis and RIPK3 for necroptosis. Unexpectedly, OTULIN mutant mice that lacked caspase 8 and RIPK3 died in the perinatal period, exhibiting enhanced production of type I interferon that was dependent on RIPK1. Collectively, our results indicate that OTULIN and LUBAC function in a linear pathway, and highlight a previously unrecognized interaction between linear ubiquitination, regulators of cell death, and induction of type I interferon.}, } @article {pmid29950719, year = {2018}, author = {Seeley, JJ and Baker, RG and Mohamed, G and Bruns, T and Hayden, MS and Deshmukh, SD and Freedberg, DE and Ghosh, S}, title = {Induction of innate immune memory via microRNA targeting of chromatin remodelling factors.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {114-119}, pmid = {29950719}, issn = {1476-4687}, support = {R01 AI033443/AI/NIAID NIH HHS/United States ; R21 AI116082/AI/NIAID NIH HHS/United States ; R37 AI033443/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chromatin Assembly and Disassembly/*genetics ; DNA Helicases/metabolism ; Female ; HEK293 Cells ; Humans ; Immune Tolerance/genetics/immunology ; Immunity, Innate/genetics/*immunology ; Immunologic Memory/*genetics/*immunology ; Inflammation/genetics/immunology ; Inflammation Mediators/immunology ; Lipopolysaccharides/immunology ; Macrophages/immunology ; Male ; Mice ; MicroRNAs/*genetics ; Nuclear Proteins/metabolism ; RAW 264.7 Cells ; STAT Transcription Factors/metabolism ; Sepsis/immunology ; Shock, Septic/immunology ; Transcription Factors/metabolism ; }, abstract = {Prolonged exposure to microbial products such as lipopolysaccharide can induce a form of innate immune memory that blunts subsequent responses to unrelated pathogens, known as lipopolysaccharide tolerance. Sepsis is a dysregulated systemic immune response to disseminated infection that has a high mortality rate. In some patients, sepsis results in a period of immunosuppression (known as 'immunoparalysis')1 characterized by reduced inflammatory cytokine output2, increased secondary infection3 and an increased risk of organ failure and mortality4. Lipopolysaccharide tolerance recapitulates several key features of sepsis-associated immunosuppression5. Although various epigenetic changes have previously been observed in tolerized macrophages6-8, the molecular basis of tolerance, immunoparalysis and other forms of innate immune memory has remained unclear. Here we perform a screen for tolerance-associated microRNAs and identify miR-221 and miR-222 as regulators of the functional reprogramming of macrophages during lipopolysaccharide tolerization. Prolonged stimulation with lipopolysaccharide in mice leads to increased expression of miR-221 and mir-222, both of which regulate brahma-related gene 1 (Brg1, also known as Smarca4). This increased expression causes the transcriptional silencing of a subset of inflammatory genes that depend on chromatin remodelling mediated by SWI/SNF (switch/sucrose non-fermentable) and STAT (signal transducer and activator of transcription), which in turn promotes tolerance. In patients with sepsis, increased expression of miR-221 and miR-222 correlates with immunoparalysis and increased organ damage. Our results show that specific microRNAs can regulate macrophage tolerization and may serve as biomarkers of immunoparalysis and poor prognosis in patients with sepsis.}, } @article {pmid29950718, year = {2018}, author = {Micheli, M and Farnocchia, D and Meech, KJ and Buie, MW and Hainaut, OR and Prialnik, D and Schörghofer, N and Weaver, HA and Chodas, PW and Kleyna, JT and Weryk, R and Wainscoat, RJ and Ebeling, H and Keane, JV and Chambers, KC and Koschny, D and Petropoulos, AE}, title = {Non-gravitational acceleration in the trajectory of 1I/2017 U1 ('Oumuamua).}, journal = {Nature}, volume = {559}, number = {7713}, pages = {223-226}, doi = {10.1038/s41586-018-0254-4}, pmid = {29950718}, issn = {1476-4687}, abstract = {'Oumuamua (1I/2017 U1) is the first known object of interstellar origin to have entered the Solar System on an unbound and hyperbolic trajectory with respect to the Sun1. Various physical observations collected during its visit to the Solar System showed that it has an unusually elongated shape and a tumbling rotation state1-4 and that the physical properties of its surface resemble those of cometary nuclei5,6, even though it showed no evidence of cometary activity1,5,7. The motion of all celestial bodies is governed mostly by gravity, but the trajectories of comets can also be affected by non-gravitational forces due to cometary outgassing8. Because non-gravitational accelerations are at least three to four orders of magnitude weaker than gravitational acceleration, the detection of any deviation from a purely gravity-driven trajectory requires high-quality astrometry over a long arc. As a result, non-gravitational effects have been measured on only a limited subset of the small-body population9. Here we report the detection, at 30σ significance, of non-gravitational acceleration in the motion of 'Oumuamua. We analyse imaging data from extensive observations by ground-based and orbiting facilities. This analysis rules out systematic biases and shows that all astrometric data can be described once a non-gravitational component representing a heliocentric radial acceleration proportional to r-2 or r-1 (where r is the heliocentric distance) is included in the model. After ruling out solar-radiation pressure, drag- and friction-like forces, interaction with solar wind for a highly magnetized object, and geometric effects originating from 'Oumuamua potentially being composed of several spatially separated bodies or having a pronounced offset between its photocentre and centre of mass, we find comet-like outgassing to be a physically viable explanation, provided that 'Oumuamua has thermal properties similar to comets.}, } @article {pmid29950717, year = {2018}, author = {Gruszczyk, J and Huang, RK and Chan, LJ and Menant, S and Hong, C and Murphy, JM and Mok, YF and Griffin, MDW and Pearson, RD and Wong, W and Cowman, AF and Yu, Z and Tham, WH}, title = {Cryo-EM structure of an essential Plasmodium vivax invasion complex.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {135-139}, doi = {10.1038/s41586-018-0249-1}, pmid = {29950717}, issn = {1476-4687}, support = {208693//Wellcome Trust/United Kingdom ; 090770//Wellcome Trust/United Kingdom ; }, mesh = {Antibodies, Monoclonal/immunology/pharmacology ; Antigens, CD/chemistry/genetics/metabolism/ultrastructure ; Binding Sites ; *Cryoelectron Microscopy ; Humans ; Malaria Vaccines/immunology ; Models, Molecular ; Mutation ; Plasmodium vivax/*chemistry/cytology/genetics/*ultrastructure ; Protozoan Proteins/antagonists & inhibitors/*chemistry/genetics/*ultrastructure ; Receptors, Transferrin/chemistry/genetics/metabolism/ultrastructure ; Reticulocytes/metabolism ; Structure-Activity Relationship ; Transferrin/chemistry/metabolism/ultrastructure ; }, abstract = {Plasmodium vivax is the most widely distributed malaria parasite that infects humans1. P. vivax invades reticulocytes exclusively, and successful entry depends on specific interactions between the P. vivax reticulocyte-binding protein 2b (PvRBP2b) and transferrin receptor 1 (TfR1)2. TfR1-deficient erythroid cells are refractory to invasion by P. vivax, and anti-PvRBP2b monoclonal antibodies inhibit reticulocyte binding and block P. vivax invasion in field isolates2. Here we report a high-resolution cryo-electron microscopy structure of a ternary complex of PvRBP2b bound to human TfR1 and transferrin, at 3.7 Å resolution. Mutational analyses show that PvRBP2b residues involved in complex formation are conserved; this suggests that antigens could be designed that act across P. vivax strains. Functional analyses of TfR1 highlight how P. vivax hijacks TfR1, an essential housekeeping protein, by binding to sites that govern host specificity, without affecting its cellular function of transporting iron. Crystal and solution structures of PvRBP2b in complex with antibody fragments characterize the inhibitory epitopes. Our results establish a structural framework for understanding how P. vivax reticulocyte-binding protein engages its receptor and the molecular mechanism of inhibitory monoclonal antibodies, providing important information for the design of novel vaccine candidates.}, } @article {pmid29950716, year = {2018}, author = {Gorthi, A and Romero, JC and Loranc, E and Cao, L and Lawrence, LA and Goodale, E and Iniguez, AB and Bernard, X and Masamsetti, VP and Roston, S and Lawlor, ER and Toretsky, JA and Stegmaier, K and Lessnick, SL and Chen, Y and Bishop, AJR}, title = {Author Correction: EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {E11}, doi = {10.1038/s41586-018-0230-z}, pmid = {29950716}, issn = {1476-4687}, abstract = {In this Letter, the sentence beginning "This work was funded…." in the Acknowledgements should have read "CPRIT (RP140105) to J.C.R." rather than "CPRIT (RP150445) to J.C.R." This error has been corrected online.}, } @article {pmid29950696, year = {2018}, author = {Petersen, JM and Kemper, A and Gruber-Vodicka, H and Cardini, U and van der Geest, M and Kleiner, M and Bulgheresi, S and Mußmann, M and Herbold, C and Seah, BKB and Antony, CP and Liu, D and Belitz, A and Weber, M}, title = {Author Correction: Chemosynthetic symbionts of marine invertebrate animals are capable of nitrogen fixation.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {961}, doi = {10.1038/s41564-018-0196-5}, pmid = {29950696}, issn = {2058-5276}, abstract = {In this Article, the completeness and number of contigs for draft genomes from two individuals of Laxus oneistus are incorrect in the main text, although the correct information is included in Table 1. The original and corrected versions of the relevant sentence are shown in the correction notice.}, } @article {pmid29950695, year = {2018}, author = {Kwong, WK and Zheng, H and Moran, NA}, title = {Author Correction: Convergent evolution of a modified, acetate-driven TCA cycle in bacteria.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {960}, doi = {10.1038/s41564-018-0195-6}, pmid = {29950695}, issn = {2058-5276}, abstract = {In this Brief Communication, the authors omitted references to several previous studies that have demonstrated that the TCA variant shown has also been found in several other bacterial species, specifically among some anaerobic Deltaproteobacteria. The Brief Communication focused on showing that this variant is more widespread than previously known, particularly in animal-associated bacteria. Using genetic approaches, Kwong et al. demonstrated this alternative cycle in additional, distantly related organisms. Thus, the previous work does not affect the results of the advance provided. However, the previous studies are relevant to this topic and should have been cited, and Kwong et al. apologize for this for the omission. Citations to several of the studies should have been included as refs 9-13 in the text as shown.}, } @article {pmid29950650, year = {2018}, author = {Jia, H}, title = {Core values.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S14-S15}, doi = {10.1038/d41586-018-05486-2}, pmid = {29950650}, issn = {1476-4687}, } @article {pmid29950649, year = {2018}, author = {}, title = {Making waves.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S25-S26}, doi = {10.1038/d41586-018-05558-3}, pmid = {29950649}, issn = {1476-4687}, } @article {pmid29950648, year = {2018}, author = {Mallapaty, S}, title = {Casting a net for knowledge.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S10-S11}, doi = {10.1038/d41586-018-05487-1}, pmid = {29950648}, issn = {1476-4687}, } @article {pmid29950647, year = {2018}, author = {Kingsford, R}, title = {Zoom in on the big picture.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S21}, doi = {10.1038/d41586-018-05483-5}, pmid = {29950647}, issn = {1476-4687}, } @article {pmid29950646, year = {2018}, author = {Bourzac, K}, title = {In the line of fire.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S2-S3}, doi = {10.1038/d41586-018-05489-z}, pmid = {29950646}, issn = {1476-4687}, } @article {pmid29950645, year = {2018}, author = {Armitage, C}, title = {The search for solutions.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S1}, doi = {10.1038/d41586-018-05490-6}, pmid = {29950645}, issn = {1476-4687}, } @article {pmid29950644, year = {2018}, author = {Leeming, J}, title = {Pooled resources.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S22}, doi = {10.1038/d41586-018-05482-6}, pmid = {29950644}, issn = {1476-4687}, } @article {pmid29950643, year = {2018}, author = {DeWeerdt, S}, title = {Gravitational pull.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S6-S7}, doi = {10.1038/d41586-018-05488-0}, pmid = {29950643}, issn = {1476-4687}, } @article {pmid29950642, year = {2018}, author = {Armitage, C}, title = {Paving the way to an urban future.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S18}, doi = {10.1038/d41586-018-05485-3}, pmid = {29950642}, issn = {1476-4687}, } @article {pmid29950641, year = {2018}, author = {Savage, N}, title = {Big data goes green.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S19}, doi = {10.1038/d41586-018-05484-4}, pmid = {29950641}, issn = {1476-4687}, } @article {pmid29950640, year = {2018}, author = {}, title = {A guide to the Nature Index.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {S27}, doi = {10.1038/d41586-018-05559-2}, pmid = {29950640}, issn = {1476-4687}, } @article {pmid29950639, year = {2018}, author = {}, title = {Five hubs of Asian science.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {499}, doi = {10.1038/d41586-018-05504-3}, pmid = {29950639}, issn = {1476-4687}, mesh = {Hong Kong ; Malaysia ; Republic of Korea ; Research/economics/organization & administration/standards/*trends ; Singapore ; Taiwan ; }, } @article {pmid29950638, year = {2018}, author = {}, title = {Asteroid defence, marijuana drug and Koko the gorilla.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {490-491}, doi = {10.1038/d41586-018-05511-4}, pmid = {29950638}, issn = {1476-4687}, } @article {pmid29950637, year = {2018}, author = {Van Noorden, R}, title = {Science in East Asia - by the numbers.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {500-501}, doi = {10.1038/d41586-018-05505-2}, pmid = {29950637}, issn = {1476-4687}, mesh = {Bibliometrics ; Gross Domestic Product ; Hong Kong ; Malaysia ; Republic of Korea ; Research Personnel/statistics & numerical data ; Research Report ; Research Support as Topic/economics ; Science/economics/standards/*statistics & numerical data ; Sex Distribution ; Sex Factors ; Singapore ; Taiwan ; Universities/standards ; }, } @article {pmid29950636, year = {2018}, author = {Gewin, V}, title = {How to build a lab in East Asia's science hot spots.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {625-627}, doi = {10.1038/d41586-018-05513-2}, pmid = {29950636}, issn = {1476-4687}, mesh = {Career Mobility ; Far East ; Fellowships and Scholarships ; Hong Kong ; Laboratories/economics/*organization & administration ; Malaysia ; *Personnel Selection ; Republic of Korea ; *Research Personnel/economics/education ; Singapore ; Workforce ; }, } @article {pmid29950635, year = {2018}, author = {Ismail, A}, title = {How Malaysian science can improve lives as well as the economy.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {514-515}, doi = {10.1038/d41586-018-05509-y}, pmid = {29950635}, issn = {1476-4687}, mesh = {Animals ; Global Warming ; Gross Domestic Product ; Humans ; Inventions/economics ; Malaysia/epidemiology ; Obesity/epidemiology ; Science/*economics/organization & administration/*trends ; }, } @article {pmid29950633, year = {2018}, author = {Witze, A}, title = {Mysteries of Indian monsoon probed in Bay of Bengal.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {493-494}, doi = {10.1038/d41586-018-05492-4}, pmid = {29950633}, issn = {1476-4687}, mesh = {Atmosphere ; Bays ; Humans ; India ; Indian Ocean ; *Rain ; *Seasons ; Water Supply ; }, } @article {pmid29950632, year = {2018}, author = {Yeom, HW}, title = {South Korean science needs restructuring.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {511-513}, doi = {10.1038/d41586-018-05508-z}, pmid = {29950632}, issn = {1476-4687}, mesh = {Budgets ; *Organizational Innovation ; Republic of Korea ; Research Report ; Research Support as Topic ; Science/economics/*organization & administration/*trends ; }, } @article {pmid29950631, year = {2018}, author = {Cyranoski, D and Law, YH and Ong, S and Phillips, N and Zastrow, M}, title = {Science stars of East Asia.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {502-510}, doi = {10.1038/d41586-018-05506-1}, pmid = {29950631}, issn = {1476-4687}, mesh = {*Air Pollution, Indoor/adverse effects/analysis/prevention & control/statistics & numerical data ; Animals ; Asthma/epidemiology/etiology ; *Biofuels/supply & distribution ; Biomarkers, Tumor/genetics ; Breast Neoplasms/*genetics ; Copper/chemistry ; Coronavirus Infections/epidemiology/prevention & control/virology ; Crops, Agricultural/*genetics ; Feces/parasitology ; Female ; Gene Editing ; Gold/chemistry ; Graphite/chemical synthesis/*chemistry ; *Helminthiasis/epidemiology/parasitology ; Hong Kong/epidemiology ; Humans ; Influenza A Virus, H5N1 Subtype/pathogenicity ; Korea ; Lighting/*instrumentation ; Malaysia ; MicroRNAs/biosynthesis/*genetics ; *Severe Acute Respiratory Syndrome/epidemiology/prevention & control/virology ; Silicon/chemistry ; Singapore/epidemiology ; *Speech Recognition Software ; Taiwan/epidemiology ; Video Recording ; }, } @article {pmid29950630, year = {2018}, author = {Stevelink, R and Kok, G}, title = {Young scientists aim to prioritize patients.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {519}, doi = {10.1038/d41586-018-05556-5}, pmid = {29950630}, issn = {1476-4687}, mesh = {*Biomedical Research ; Humans ; }, } @article {pmid29950629, year = {2018}, author = {Campbell, P}, title = {Nature editor bids farewell.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {486}, doi = {10.1038/d41586-018-05525-y}, pmid = {29950629}, issn = {1476-4687}, } @article {pmid29950628, year = {2018}, author = {Mateo-Tomás, P and Olea, PP}, title = {A call for IPBES to fix policies that harm scavengers.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {519}, doi = {10.1038/d41586-018-05557-4}, pmid = {29950628}, issn = {1476-4687}, mesh = {Animals ; Biodiversity ; *Birds ; *Conservation of Natural Resources ; Diclofenac/*toxicity ; Environmental Pollutants/*toxicity ; Pakistan ; Population Dynamics ; }, } @article {pmid29950627, year = {2018}, author = {Heuer, L}, title = {AI could threaten pharmaceutical patents.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {519}, doi = {10.1038/d41586-018-05555-6}, pmid = {29950627}, issn = {1476-4687}, mesh = {Artificial Intelligence ; *Drug Discovery ; Drug Industry ; *Legislation, Drug ; Patents as Topic ; Pharmaceutical Preparations ; }, } @article {pmid29950626, year = {2018}, author = {Sonne, C and Alstrup, AKO}, title = {One wolf shot in Denmark is too many.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {519}, doi = {10.1038/d41586-018-05554-7}, pmid = {29950626}, issn = {1476-4687}, mesh = {Animals ; Conservation of Natural Resources/*legislation & jurisprudence ; Denmark ; Endangered Species/*legislation & jurisprudence ; European Union ; Female ; United Nations/*legislation & jurisprudence ; *Wolves ; }, } @article {pmid29950625, year = {2018}, author = {Keller, M and Prusiner, S}, title = {Citations must default to the online publication date.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {519}, doi = {10.1038/d41586-018-05387-4}, pmid = {29950625}, issn = {1476-4687}, mesh = {Bibliometrics ; Periodicals as Topic ; *Prions ; Publications ; *Publishing ; }, } @article {pmid29950624, year = {2018}, author = {Maayani, S and Dahan, R and Kligerman, Y and Moses, E and Hassan, AU and Jing, H and Nori, F and Christodoulides, DN and Carmon, T}, title = {Flying couplers above spinning resonators generate irreversible refraction.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {569-572}, doi = {10.1038/s41586-018-0245-5}, pmid = {29950624}, issn = {1476-4687}, abstract = {Creating optical components that allow light to propagate in only one direction-that is, that allow non-reciprocal propagation or 'isolation' of light-is important for a range of applications. Non-reciprocal propagation of sound can be achieved simply by using mechanical components that spin1,2. Spinning also affects de Broglie waves 3 , so a similar idea could be applied in optics. However, the extreme rotation rates that would be required, owing to light travelling much faster than sound, lead to unwanted wobbling. This wobbling makes it difficult to maintain the separation between the spinning devices and the couplers to within tolerance ranges of several nanometres, which is essential for critical coupling4,5. Consequently, previous applications of optical6-17 and optomechanical10,17-20 isolation have used alternative methods. In hard-drive technology, the magnetic read heads of a hard-disk drive fly aerodynamically above the rapidly rotating disk with nanometre precision, separated by a thin film of air with near-zero drag that acts as a lubrication layer 21 . Inspired by this, here we report the fabrication of photonic couplers (tapered fibres that couple light into the resonators) that similarly fly above spherical resonators with a separation of only a few nanometres. The resonators spin fast enough to split their counter-circulating optical modes, making the fibre coupler transparent from one side while simultaneously opaque from the other-that is, generating irreversible transmission. Our setup provides 99.6 per cent isolation of light in standard telecommunication fibres, of the type used for fibre-based quantum interconnects 22 . Unlike flat geometries, such as between a magnetic head and spinning disk, the saddle-like, convex geometry of the fibre and sphere in our setup makes it relatively easy to bring the two closer together, which could enable surface-science studies at nanometre-scale separations.}, } @article {pmid29950623, year = {2018}, author = {Postberg, F and Khawaja, N and Abel, B and Choblet, G and Glein, CR and Gudipati, MS and Henderson, BL and Hsu, HW and Kempf, S and Klenner, F and Moragas-Klostermeyer, G and Magee, B and Nölle, L and Perry, M and Reviol, R and Schmidt, J and Srama, R and Stolz, F and Tobie, G and Trieloff, M and Waite, JH}, title = {Macromolecular organic compounds from the depths of Enceladus.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {564-568}, pmid = {29950623}, issn = {1476-4687}, support = {724908//European Research Council/International ; }, mesh = {Exobiology ; Extraterrestrial Environment/*chemistry ; Ice/analysis ; *Saturn ; Volatilization ; }, abstract = {Saturn's moon Enceladus harbours a global water ocean 1 , which lies under an ice crust and above a rocky core 2 . Through warm cracks in the crust 3 a cryo-volcanic plume ejects ice grains and vapour into space4-7 that contain materials originating from the ocean8,9. Hydrothermal activity is suspected to occur deep inside the porous core10-12, powered by tidal dissipation 13 . So far, only simple organic compounds with molecular masses mostly below 50 atomic mass units have been observed in plume material6,14,15. Here we report observations of emitted ice grains containing concentrated and complex macromolecular organic material with molecular masses above 200 atomic mass units. The data constrain the macromolecular structure of organics detected in the ice grains and suggest the presence of a thin organic-rich film on top of the oceanic water table, where organic nucleation cores generated by the bursting of bubbles allow the probing of Enceladus' organic inventory in enhanced concentrations.}, } @article {pmid29950622, year = {2018}, author = {Esat, T and Friedrich, N and Tautz, FS and Temirov, R}, title = {A standing molecule as a single-electron field emitter.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {573-576}, doi = {10.1038/s41586-018-0223-y}, pmid = {29950622}, issn = {1476-4687}, abstract = {Scanning probe microscopy makes it possible to image and spectroscopically characterize nanoscale objects, and to manipulate1-3 and excite4-8 them; even time-resolved experiments are now routinely achieved9,10. This combination of capabilities has enabled proof-of-principle demonstrations of nanoscale devices, including logic operations based on molecular cascades 11 , a single-atom transistor 12 , a single-atom magnetic memory cell 13 and a kilobyte atomic memory 14 . However, a key challenge is fabricating device structures that can overcome their attraction to the underlying surface and thus protrude from the two-dimensional flatlands of the surface. Here we demonstrate the fabrication of such a structure: we use the tip of a scanning probe microscope to lift a large planar aromatic molecule (3,4,9,10-perylenetetracarboxylic-dianhydride) into an upright, standing geometry on a pedestal of two metal (silver) adatoms. This atypical and surprisingly stable upright orientation of the single molecule, which under all known circumstances adsorbs flat on metals15,16, enables the system to function as a coherent single-electron field emitter. We anticipate that other metastable adsorbate configurations might also be accessible, thereby opening up the third dimension for the design of functional nanostructures on surfaces.}, } @article {pmid29950621, year = {2018}, author = {Choat, B and Brodribb, TJ and Brodersen, CR and Duursma, RA and López, R and Medlyn, BE}, title = {Triggers of tree mortality under drought.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {531-539}, doi = {10.1038/s41586-018-0240-x}, pmid = {29950621}, issn = {1476-4687}, mesh = {Acclimatization/physiology ; *Droughts ; Natural Disasters ; Stress, Physiological/*physiology ; Trees/anatomy & histology/genetics/*physiology ; Water/metabolism/physiology ; Xylem/metabolism ; }, abstract = {Severe droughts have caused widespread tree mortality across many forest biomes with profound effects on the function of ecosystems and carbon balance. Climate change is expected to intensify regional-scale droughts, focusing attention on the physiological basis of drought-induced tree mortality. Recent work has shown that catastrophic failure of the plant hydraulic system is a principal mechanism involved in extensive crown death and tree mortality during drought, but the multi-dimensional response of trees to desiccation is complex. Here we focus on the current understanding of tree hydraulic performance under drought, the identification of physiological thresholds that precipitate mortality and the mechanisms of recovery after drought. Building on this, we discuss the potential application of hydraulic thresholds to process-based models that predict mortality.}, } @article {pmid29950620, year = {2018}, author = {Bouvier, LC and Costa, MM and Connelly, JN and Jensen, NK and Wielandt, D and Storey, M and Nemchin, AA and Whitehouse, MJ and Snape, JF and Bellucci, JJ and Moynier, F and Agranier, A and Gueguen, B and Schönbächler, M and Bizzarro, M}, title = {Evidence for extremely rapid magma ocean crystallization and crust formation on Mars.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {586-589}, pmid = {29950620}, issn = {1476-4687}, support = {616027//European Research Council/International ; }, abstract = {The formation of a primordial crust is a critical step in the evolution of terrestrial planets but the timing of this process is poorly understood. The mineral zircon is a powerful tool for constraining crust formation because it can be accurately dated with the uranium-to-lead (U-Pb) isotopic decay system and is resistant to subsequent alteration. Moreover, given the high concentration of hafnium in zircon, the lutetium-to-hafnium (176Lu-176Hf) isotopic decay system can be used to determine the nature and formation timescale of its source reservoir1-3. Ancient igneous zircons with crystallization ages of around 4,430 million years (Myr) have been reported in Martian meteorites that are believed to represent regolith breccias from the southern highlands of Mars4,5. These zircons are present in evolved lithologies interpreted to reflect re-melted primary Martian crust 4 , thereby potentially providing insight into early crustal evolution on Mars. Here, we report concomitant high-precision U-Pb ages and Hf-isotope compositions of ancient zircons from the NWA 7034 Martian regolith breccia. Seven zircons with mostly concordant U-Pb ages define 207Pb/206Pb dates ranging from 4,476.3 ± 0.9 Myr ago to 4,429.7 ± 1.0 Myr ago, including the oldest directly dated material from Mars. All zircons record unradiogenic initial Hf-isotope compositions inherited from an enriched, andesitic-like crust extracted from a primitive mantle no later than 4,547 Myr ago. Thus, a primordial crust existed on Mars by this time and survived for around 100 Myr before it was reworked, possibly by impacts4,5, to produce magmas from which the zircons crystallized. Given that formation of a stable primordial crust is the end product of planetary differentiation, our data require that the accretion, core formation and magma ocean crystallization on Mars were completed less than 20 Myr after the formation of the Solar System. These timescales support models that suggest extremely rapid magma ocean crystallization leading to a gravitationally unstable stratified mantle, which subsequently overturns, resulting in decompression melting of rising cumulates and production of a primordial basaltic to andesitic crust6,7.}, } @article {pmid29950316, year = {2018}, author = {Zapparoli, L and Seghezzi, S and Scifo, P and Zerbi, A and Banfi, G and Tettamanti, M and Paulesu, E}, title = {Dissecting the neurofunctional bases of intentional action.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7440-7445}, pmid = {29950316}, issn = {1091-6490}, mesh = {Adult ; *Connectome ; *Diffusion Tensor Imaging ; Female ; *Gyrus Cinguli/diagnostic imaging/physiology ; Humans ; *Intention ; *Magnetic Resonance Imaging ; Male ; *Models, Neurological ; *Motor Cortex/diagnostic imaging/physiology ; }, abstract = {Here we challenge and present evidence that expands the what, when, and whether anatomical model of intentional action, which states that internally driven decisions about the content and timing of our actions and about whether to act at all depend on separable neural systems, anatomically segregated along the medial wall of the frontal lobe. In our fMRI event-related paradigm, subjects acted following conditional cues or following their intentions. The content of the actions, their timing, or their very occurrence were the variables investigated, together with the modulating factor of intentionality. Besides a shared activation of the pre-supplementary motor area (pre-SMA) and anterior cingulate cortex (ACC) for all components and the SMA proper for the when component, we found specific activations beyond the mesial prefrontal wall involving the parietal cortex for the what component or subcortical gray structures for the when component. Moreover, we found behavioral, functional, anatomical, and brain connectivity evidence that the self-driven decisions on whether to act require a higher interhemispheric cooperation: This was indexed by a specific activation of the corpus callosum whereby the less the callosal activation, the greater was the decision cost at the time of the action in the whether trials. Furthermore, tractography confirmed that the fibers passing through the callosal focus of activation connect the two sides of the frontal lobes involved in intentional trials. This is evidence of non-unitary neural foundations for the processes involved in intentional actions with the pre-SMA/ACC operating as an intentional hub. These findings may guide the exploration of specific instances of disturbed intentionality.}, } @article {pmid29950315, year = {2018}, author = {Gage, MC and Bécares, N and Louie, R and Waddington, KE and Zhang, Y and Tittanegro, TH and Rodríguez-Lorenzo, S and Jathanna, A and Pourcet, B and Pello, OM and De la Rosa, JV and Castrillo, A and Pineda-Torra, I}, title = {Disrupting LXRα phosphorylation promotes FoxM1 expression and modulates atherosclerosis by inducing macrophage proliferation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6556-E6565}, pmid = {29950315}, issn = {1091-6490}, support = {G0801278//Medical Research Council/United Kingdom ; PG/13/10/30000//British Heart Foundation/United Kingdom ; FS/12/59/30649//British Heart Foundation/United Kingdom ; }, mesh = {Amino Acid Substitution ; Animals ; Atherosclerosis/genetics/*metabolism/pathology ; Cell Proliferation ; Forkhead Box Protein M1/*biosynthesis/genetics ; *Gene Expression Regulation ; Liver X Receptors/genetics/*metabolism ; Macrophages/*metabolism/pathology ; Mice ; Mice, Knockout ; *Mutation, Missense ; Phosphorylation ; }, abstract = {Macrophages are key immune cells for the initiation and development of atherosclerotic lesions. However, the macrophage regulatory nodes that determine how lesions progress in response to dietary challenges are not fully understood. Liver X receptors (LXRs) are sterol-regulated transcription factors that play a central role in atherosclerosis by integrating cholesterol homeostasis and immunity. LXR pharmacological activation elicits a robust antiatherosclerotic transcriptional program in macrophages that can be affected by LXRα S196 phosphorylation in vitro. To investigate the impact of these transcriptional changes in atherosclerosis development, we have generated mice carrying a Ser-to-Ala mutation in myeloid cells in the LDL receptor (LDLR)-deficient atherosclerotic background (M-S196ALdlr-KO). M-S196ALdlr-KO mice fed a high-fat diet exhibit increased atherosclerotic plaque burden and lesions with smaller necrotic cores and thinner fibrous caps. These diet-induced phenotypic changes are consistent with a reprogramed macrophage transcriptome promoted by LXRα-S196A during atherosclerosis development. Remarkably, expression of several proliferation-promoting factors, including the protooncogene FoxM1 and its targets, is induced by LXRα-S196A. This is consistent with increased proliferation of plaque-resident cells in M-S196ALdlr-KO mice. Moreover, disrupted LXRα phosphorylation increases expression of phagocytic molecules, resulting in increased apoptotic cell removal by macrophages, explaining the reduced necrotic cores. Finally, the macrophage transcriptome promoted by LXRα-S196A under dietary perturbation is markedly distinct from that revealed by LXR ligand activation, highlighting the singularity of this posttranslational modification. Overall, our findings demonstrate that LXRα phosphorylation at S196 is an important determinant of atherosclerotic plaque development through selective changes in gene transcription that affect multiple pathways.}, } @article {pmid29950181, year = {2018}, author = {Pendleton, AL and Shen, F and Taravella, AM and Emery, S and Veeramah, KR and Boyko, AR and Kidd, JM}, title = {Comparison of village dog and wolf genomes highlights the role of the neural crest in dog domestication.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {64}, pmid = {29950181}, issn = {1741-7007}, support = {R24 GM082910/GM/NIGMS NIH HHS/United States ; T32 HG000040/HG/NHGRI NIH HHS/United States ; R01 GM103961/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Domesticated from gray wolves between 10 and 40 kya in Eurasia, dogs display a vast array of phenotypes that differ from their ancestors, yet mirror other domesticated animal species, a phenomenon known as the domestication syndrome. Here, we use signatures persisting in dog genomes to identify genes and pathways possibly altered by the selective pressures of domestication.

RESULTS: Whole-genome SNP analyses of 43 globally distributed village dogs and 10 wolves differentiated signatures resulting from domestication rather than breed formation. We identified 246 candidate domestication regions containing 10.8 Mb of genome sequence and 429 genes. The regions share haplotypes with ancient dogs, suggesting that the detected signals are not the result of recent selection. Gene enrichments highlight numerous genes linked to neural crest and central nervous system development as well as neurological function. Read depth analysis suggests that copy number variation played a minor role in dog domestication.

CONCLUSIONS: Our results identify genes that act early in embryogenesis and can confer phenotypes distinguishing domesticated dogs from wolves, such as tameness, smaller jaws, floppy ears, and diminished craniofacial development as the targets of selection during domestication. These differences reflect the phenotypes of the domestication syndrome, which can be explained by alterations in the migration or activity of neural crest cells during development. We propose that initial selection during early dog domestication was for behavior, a trait influenced by genes which act in the neural crest, which secondarily gave rise to the phenotypes of modern dogs.}, } @article {pmid29949501, year = {2018}, author = {Mekadim, C and Killer, J and Pechar, R and Mrázek, J}, title = {Variable regions of the glyS, infB and rplB genes usable as novel genetic markers for identification and phylogenetic purposes of genera belonging to the family Propionibacteriaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2697-2705}, doi = {10.1099/ijsem.0.002873}, pmid = {29949501}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Chickens/microbiology ; DNA, Bacterial/genetics ; Dairy Products/microbiology ; Female ; *Genes, Bacterial ; Genetic Markers ; Humans ; *Phylogeny ; Propionibacteriaceae/*classification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {No common, unique genetic markers applicable to classification and phylogenetics for significant genera within the Propionibacteriaceae family have been suggested yet. Therefore, the aim of the study was to propose those genes in the genera Acidipropionibacterium, Cutibacterium, Propionibacterium and Pseudopropionibacterium. These genera were recently elicited from the genus Propionibacterium through whole genomic analyses. Three housekeeping genes, glyS, infB and rplB, were selected from many others according to the requirements for appropriate classification/phylogenetic markers. Concrete fragments of the genes were amplified using specific primers in most of the type (14) and 11 wild strains (originating from dairy products, human skin and the crop of a laying hen) recently classified into the genus Propionibacterium. Sequences obtained from amplicons were used to perform gene statistics and phylogenetic analyses with respect to applicability in classification, typing and phylogeny. The 16S rRNA gene sequences, still considered relevant in spite of its proven shortcomings as a basic tool for evaluation of bacterial phylogeny, were used as a baseline for comparative analyses. The statistics of the gene sequences revealed that the variable regions of all three genes have higher resolution capabilities among strains examined compared to the 16S rRNA gene analysis. Phylogenetic analyses based on individual gene sequences and their concatenate enabled to distinguish clusters of species belonging to the genera Acidipropionibacterium, Cutibacterium and Propionibacterium, which corresponds with a recently reported genomic study. Thus, the crucial importance of this study is the economically advantageous classification and typing of propionibacterial isolates and strains through the three gene regions in contrast to the requirement for whole genomic assays.}, } @article {pmid29949500, year = {2018}, author = {Mu, Y and Jia, WB and Ke, Z and Zhuang, W and Wang, HM and Jiang, JD and Chen, K and Chen, Q}, title = {Shinella pollutisoli sp. nov., isolated from tetrabromobisphenol A-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2602-2606}, doi = {10.1099/ijsem.0.002883}, pmid = {29949500}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; Polybrominated Biphenyls ; RNA, Ribosomal, 16S/genetics ; Rhizobiaceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil Microbiology ; Soil Pollutants ; Ubiquinone/chemistry ; }, abstract = {Strain AH-1T, a Gram-negative, aerobic, non-spore-forming, motile, rod-shaped bacterium, was isolated from tetrabromobisphenol A-contaminated soil in China. The taxonomic position was investigated using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain AH-1T was a member of the genus Shinella and showed the highest sequence similarity to Shinella fusca DC-196T (97.7 %), Shinella granuli Ch06T (97.3 %), Shinella daejeonensis MJ02T (97.1 %) and Shinella yambaruensis MS4T (96.8 %), and lower (<96.7 %) sequence similarity to other known Shinella species. Chemotaxonomic analysis revealed that strain AH-1T possessed Q-10 as the major isoprenoid quinone; and summed feature 8 (C18 : 1ω6c/C18 : 1ω7c), C16 : 0, C12 : 0 aldehyde, C18 : 0, C19 : 0 cyclo ω8c and C18 : 0 3-OH were the predominant fatty acids. Strain AH-1T showed low DNA-DNA relatedness to S. fusca DC-196T (28.6±5.7 %), S. granuli Ch06T (43.7±3.8 %) and S. daejeonensis MJ02T (48.1±2.6 %). The DNA G+C content was 68.2 mol%. Based on the phylogenetic and phenotypic characteristics, chemotaxonomic data and DNA-DNA hybridization, strain AH-1T is considered a novel species of the genus Shinella, for which the name Shinella pollutisoli sp. nov. (type strain AH-1T=KCTC 52677T=CCTCC AB 2017242T) is proposed.}, } @article {pmid29949499, year = {2018}, author = {Zhang, L and Wang, KL and Yin, Q and Liang, JY and Xu, Y}, title = {Ruegeria kandeliae sp. nov., isolated from the rhizosphere soil of a mangrove plant Kandelia candel.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2653-2658}, doi = {10.1099/ijsem.0.002894}, pmid = {29949499}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hong Kong ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhizophoraceae/*microbiology ; *Rhizosphere ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative, rod-shaped and motile bacterium, designated strain J95T, was isolated from the rhizosphere soil of a mangrove plant Kandeliacandel (L.) Druce in Mai Po Nature Reserve, Hong Kong. Growth of strain J95T was observed at pH 5.0-8.5 (optimum, 6.0-7.0), between 10-40 °C (30-37 °C) and in the presence of 0-9 % (w/v) NaCl (0.5-3 %). Chemotaxonomic analysis showed ubiquinone-10 as the predominant respiratory quinone and C18 : 1ω7c and C19 : 0 cycloω8c as the major fatty acids. The major polar lipids were lipid, aminolipid, phospholipid, phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. The genomic contained a circular chromosome of 5.48 Mb with a DNA G+C content of 65.7 mol%. The genome included 5299 genes. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain J95T belongs to the genus Ruegeria with highest sequence similarity (96.8 %) to the type strain Ruegeria marina ZH17T. The combined phenotypic, chemotaxonomic and phylogenetic data suggested that strain J95T represents a novel species of the genus Ruegeria, for which the name Ruegeria kandeliae sp. nov. is proposed. The type strain is J95T (=MCCC 1K03284T=DSM 104293T).}, } @article {pmid29949498, year = {2018}, author = {Barretto, DA and Avchar, R and Carvalho, C and Sampaio, JP and Vootla, SK and Baghela, A}, title = {Blastobotrys bombycis sp. nov., a d-xylose-fermenting yeast isolated from the gut of the silkworm larva Bombyx mori.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2638-2643}, doi = {10.1099/ijsem.0.002890}, pmid = {29949498}, issn = {1466-5034}, mesh = {Animals ; Bombyx/*microbiology ; DNA, Fungal/genetics ; Fermentation ; Gastrointestinal Tract/microbiology ; Larva ; Mycological Typing Techniques ; *Phylogeny ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Xylose/metabolism ; }, abstract = {The gut of insects harbors a yeast community that is still poorly understood. Here, a novel species of the ascomycetous genus Blastobotrys is proposed based on a yeast strain isolated from the larval gut of the silkworm Bombyx mori (Order Lepidoptera). The novel species is closely related to Blastobotrys aristata and Blastobotrys elegans on the basis of the results of molecular phylogenetic analyses. A preliminary screening revealed that it produces 1.5 g l-1 ethanol by fermenting 5 % d-xylose. The novel species, that represents the first report, to our knowledge, of yeast isolation from silkworms, is described as Blastobotrys bombycis sp. nov. (type strain RAAB001T=CBS 15274T=PYCC 8105T=MCC 1427T; MycoBank accession number MB 825095).}, } @article {pmid29948009, year = {2018}, author = {Gupta, P and Mankere, B and Chekkoora Keloth, S and Tuteja, U and Chelvam, KT}, title = {Generation and In Vivo Characterization of Tn5-Induced Biofilm Mutants of Vibrio cholerae O139.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1324-1333}, pmid = {29948009}, issn = {1432-0991}, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; *Biofilms ; DNA Transposable Elements ; Gene Expression Regulation, Bacterial ; Humans ; Intestines/microbiology ; Mice ; Mice, Inbred BALB C ; *Mutagenesis, Insertional ; Vibrio cholerae O139/*genetics/growth & development/physiology ; }, abstract = {The Gram-negative bacterium Vibrio cholerae is a unique pathogen with an ability to colonize human intestine as well as outside environments. The biofilm, an organized polymeric structure produced by this bacterium known to be a significant factor for the survival and persistence in hostile conditions. However, the direct role of biofilm formation by this bacterium in environmental persistence, in vivo colonization, and pathogenesis remains unexplored. In this study, we have generated biofilm-altered Tn5 mutants of V. cholerae O139 and evaluated their in vivo colonization ability on mouse model. These Tn5 mutants were found to harbor an independent, single Tn5 insertion in their genome. The DNA sequence analysis revealed that genomic region wherein Tn5 insertion occurred is identified to be involved in functions like LPS biosynthesis, efflux transporters, motility, purine metabolism, stringent response, VPS synthesis, and a hypothetical protein of unknown function. In single-strain infection with the planktonic culture, the biofilm-altered as well as the biofilm intermediate mutants were found to be more or less similar in their intestinal colonization ability, however infection with their biofilm form, a marked difference was observed between the biofilm deficient and other biofilm forming strains. Further, in the competition experiments, biofilm deficient and proficient mutants were found reduced in their colonization ability and outcompeted by their parent strain. In conclusion, biofilm formation in V. cholerae O139 is a genetically complex process and the controlled and regulated production of biofilm appeared to be necessary for its efficient colonization of mouse intestine.}, } @article {pmid29948008, year = {2018}, author = {Wang, TS and Xie, JY and Wang, LY and Chen, SF}, title = {Paenibacillus maysiensis sp. nov., a Nitrogen-Fixing Species Isolated from the Rhizosphere Soil of Maize.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1267-1273}, pmid = {29948008}, issn = {1432-0991}, mesh = {Bacterial Typing Techniques ; Base Composition ; Fatty Acids/chemistry/metabolism ; *Nitrogen Fixation ; Paenibacillus/classification/genetics/*isolation & purification/metabolism ; Phylogeny ; Plant Roots/growth & development/microbiology ; RNA, Ribosomal, 16S ; Rhizosphere ; *Soil Microbiology ; Zea mays/growth & development/microbiology ; }, abstract = {A novel bacterium SX-49T with nitrogen-fixing capability was isolated from the rhizosphere soil of maize. Phylogenetic analysis of nifH gene fragment and 16S rRNA gene sequence revealed that the strain SX-49T is a member of the genus Paenibacillus. Values of 16S rRNA gene sequence similarity were highest between SX-49T and P. jamilae DSM 13815T (97.0%), P. brasiliensis DSM 14914T (97.8%), P. polymyxa DSM 36T (97.5%), and P. terrae DSM 15891T (98.8%). The similarity between SX-49T and other Paenibacillus species was < 97.0%. DNA-DNA hybridization values between strain SX-49T and the four type strains were P. jamilae DSM 13815T: 40.6%, P. brasiliensis DSM 14914T: 27.9%, P. polymyxa DSM 36T: 29.2%, and P. terrae DSM 15891T: 66.4%. The DNA G+C content of SX-49T was 46.4 mol%. The predominant fatty acids were anteiso-C15:0, C16:0 and iso-C16:0. The predominant isoprenoid quinone was MK-7. The genome contains 5628 putative protein-coding sequences (CDS), 6 rRNAs and 56 tRNAs. The phenotypic and genotypic characteristics, DNA-DNA relatedness, and genome features suggest that SX-49T represents a novel species of the genus Paenibacillus, and the name Paenibacillus maysiensis sp. nov. is proposed.}, } @article {pmid29947946, year = {2018}, author = {Isobe, M and Nunome, M and Katakura, K and Suzuki, H}, title = {Evolutionary Dynamics of Copy Number and Meiotic Recombination in Murine 5S rDNA: Possible Involvement of Natural Selection.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {312-323}, pmid = {29947946}, issn = {1432-1432}, support = {15K07177//Japan Society for the Promotion of Science/ ; }, abstract = {We investigated evolutionary trends of the 5S ribosomal RNA gene in the house mouse, Mus musculus. First, we assessed the 5S cluster and copy numbers in eight laboratory strains by pulsed-field gel electrophoresis. The copy numbers in seven lines were estimated to be around 130-170 copies per cluster, with 63 copies in the remaining strain, implying that the copy number can change drastically and has been maintained under certain evolutionary constraints at ~ 140 copies. Second, we addressed the frequency of meiotic recombination mediated by the 5S cluster by performing a mating experiment with laboratory strains, and found that the 5S cluster did not accelerate recombination events. Third, we surveyed recombination events of the 5S-containing chromosome region in wild mice from the Japanese Islands, where the two subspecies lineages, M. m. castaneus and M. m. musculus, are historically mingled, and found that the influence of the 5S cluster on meiotic recombination was limited. Finally, we examined the nucleotide diversity of six genes in the neighboring regions of the 5S cluster and found reduced genetic diversity in the regions on both sides of the cluster, suggesting the involvement of either positive or background selection in the population-level sequence similarity of the 5S clusters. Therefore, the mouse 5S genes are considered to be evolving toward sequence similarity within a given cluster by certain intrachromosomal mechanisms and toward sharing of a specific 5S cluster within a population by certain selective processes.}, } @article {pmid29947797, year = {2018}, author = {Smith, HL and Pavasovic, A and Surm, JM and Phillips, MJ and Prentis, PJ}, title = {Evidence for a Large Expansion and Subfunctionalization of Globin Genes in Sea Anemones.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1892-1901}, pmid = {29947797}, issn = {1759-6653}, mesh = {Animals ; Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation ; Genetic Association Studies ; Globins/*genetics ; Likelihood Functions ; Multigene Family ; Phylogeny ; Reproducibility of Results ; Sea Anemones/*genetics ; Sequence Analysis, RNA ; Transcriptome/genetics ; }, abstract = {The globin gene superfamily has been well-characterized in vertebrates, however, there has been limited research in early-diverging lineages, such as phylum Cnidaria. This study aimed to identify globin genes in multiple cnidarian lineages, and use bioinformatic approaches to characterize the evolution, structure, and expression of these genes. Phylogenetic analyses and in silico protein predictions showed that all cnidarians have undergone an expansion of globin genes, which likely have a hexacoordinate protein structure. Our protein modeling has also revealed the possibility of a single pentacoordinate globin lineage in anthozoan species. Some cnidarian globin genes displayed tissue and development specific expression with very few orthologous genes similarly expressed across species. Our phylogenetic analyses also revealed that eumetazoan globin genes form a polyphyletic relationship with vertebrate globin genes. Overall, our analyses suggest that a Ngb-like and GbX-like gene were most likely present in the globin gene repertoire for the last common ancestor of eumetazoans. The identification of a large-scale expansion and subfunctionalization of globin genes in actiniarians provides an excellent starting point to further our understanding of the evolution and function of the globin gene superfamily in early-diverging lineages.}, } @article {pmid29947761, year = {2018}, author = {Faria, VG and Martins, NE and Schlötterer, C and Sucena, É}, title = {Readapting to DCV Infection without Wolbachia: Frequency Changes of Drosophila Antiviral Alleles Can Replace Endosymbiont Protection.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1783-1791}, pmid = {29947761}, issn = {1759-6653}, support = {P 27630//Austrian Science Fund FWF/Austria ; }, mesh = {Adaptation, Physiological ; Alleles ; Animals ; Drosophila melanogaster/genetics/*microbiology/physiology/*virology ; Genome, Insect ; Host-Pathogen Interactions ; Insect Viruses/*physiology ; Polymorphism, Genetic ; *Symbiosis ; Wolbachia/*physiology ; }, abstract = {There is now ample evidence that endosymbionts can contribute to host adaptation to environmental challenges. However, how endosymbiont presence affects the adaptive trajectory and outcome of the host is yet largely unexplored. In Drosophila, Wolbachia confers protection to RNA virus infection, an effect that differs between Wolbachia strains and can be targeted by selection. Adaptation to RNA virus infections is mediated by both Wolbachia and the host, raising the question of whether adaptive genetic changes in the host vary with the presence/absence of the endosymbiont. Here, we address this question using a polymorphic D. melanogaster population previously adapted to DCV infection for 35 generations in the presence of Wolbachia, from which we removed the endosymbiont and followed survival over the subsequent 20 generations of infection. After an initial severe drop, survival frequencies upon DCV selection increased significantly, as seen before in the presence of Wolbachia. Whole-genome sequencing, revealed that the major genes involved in the first selection experiment, pastrel and Ubc-E2H, continued to be selected in Wolbachia-free D. melanogaster, with the frequencies of protective alleles being closer to fixation in the absence of Wolbachia. Our results suggest that heterogeneity in Wolbachia infection status may be sufficient to maintain polymorphisms even in the absence of costs.}, } @article {pmid29947758, year = {2018}, author = {Lake, JA and Larsen, J and Tran, DT and Sinsheimer, JS}, title = {Uncovering the Genomic Origins of Life.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1705-1714}, pmid = {29947758}, issn = {1759-6653}, support = {R01 GM053275/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA/genetics ; *Evolution, Molecular ; *Genetic Code ; *Genome ; Genomics/*methods ; *Origin of Life ; Phylogeny ; RNA/genetics ; }, abstract = {The Origin of Life Domain (OLD) is the period during which life on Earth began. Here, we derive and use a new phylogenetic algorithm to analyze Protein Families in order to reconstruct the chronological steps by which the OLD evolved. During this period, life began with the appearance of the fundamental components of life such as RNAs, DNAs, amino acids, and membranes. Chronologically, the Origin of Life preceded the Last Universal Common Ancestor, which then subsequently engendered modern life on Earth. Our phylogenetic algorithm allows us to explicitly answer previously unknown origin of life questions. Specifically, we explain and illustrate our computational methods by reconstructing the rings describing the evolution of the RNA and DNA worlds. We phylogenetically reconstruct how the RNA and DNA worlds evolved, infer the origins and chronological order of appearance of the first genetic codes, test whether the Ribosomal RNA world preceded the Membrane world, and interpret these new findings with respect to the experimental and theoretical origin of life studies by others.}, } @article {pmid29947749, year = {2018}, author = {Puerma, E and Orengo, DJ and Cruz, F and Gómez-Garrido, J and Librado, P and Salguero, D and Papaceit, M and Gut, M and Segarra, C and Alioto, TS and Aguadé, M}, title = {The High-Quality Genome Sequence of the Oceanic Island Endemic Species Drosophila guanche Reveals Signals of Adaptive Evolution in Genes Related to Flight and Genome Stability.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1956-1969}, pmid = {29947749}, issn = {1759-6653}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Base Sequence ; Chromosomes/genetics ; DNA Transposable Elements/genetics ; Drosophila/*genetics ; *Evolution, Molecular ; Flight, Animal/*physiology ; *Genes, Insect ; *Genomic Instability ; *Islands ; Molecular Sequence Annotation ; Oceans and Seas ; Phylogeny ; }, abstract = {Drosophila guanche is a member of the obscura group that originated in the Canary Islands archipelago upon its colonization by D. subobscura. It evolved into a new species in the laurisilva, a laurel forest present in wet regions that in the islands have only minor long-term weather fluctuations. Oceanic island endemic species such as D. guanche can become model species to investigate not only the relative role of drift and adaptation in speciation processes but also how population size affects nucleotide variation. Moreover, the previous identification of two satellite DNAs in D. guanche makes this species attractive for studying how centromeric DNA evolves. As a prerequisite for its establishment as a model species suitable to address all these questions, we generated a high-quality D. guanche genome sequence composed of 42 cytologically mapped scaffolds, which are assembled into six super-scaffolds (one per chromosome). The comparative analysis of the D. guanche proteome with that of twelve other Drosophila species identified 151 genes that were subject to adaptive evolution in the D. guanche lineage, with a subset of them being involved in flight and genome stability. For example, the Centromere Identifier (CID) protein, directly interacting with centromeric satellite DNA, shows signals of adaptation in this species. Both genomic analyses and FISH of the two satellites would support an ongoing replacement of centromeric satellite DNA in D. guanche.}, } @article {pmid29947602, year = {2018}, author = {Hu, Q and Zhang, L and Hang, P and Zhou, XY and Jia, WB and Li, SP and Jiang, JD}, title = {Xinfangfangia soli gen. nov., sp. nov., isolated from a diuron-polluted soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2622-2626}, doi = {10.1099/ijsem.0.002887}, pmid = {29947602}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diuron ; Fatty Acids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil Microbiology ; Soil Pollutants ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-staining-negative, non-motile and rod-shaped bacterial strain ZQBWT, which was isolated from a diuron-polluted soil collected near Nanjing, PR China, was investigated for its taxonomic position by a polyphasic approach. ZQBWT grew well at pH 6.0-12.0 (optimum, pH 7.0), 26-35 °C (optimum, 30 °C) and up to 0.5 % NaCl (optimally the absence of NaCl) in R2A broth. The major fatty acids of ZQBWT were C18 : 1ω7c (82.7 %) and C18 : 0 (5.3 %). The polar lipid profile included the major compounds phophatidylcholine, phosphatidylglycerol and phosphatidylmethylethanolamine. The only respiratory quinone was ubiquinone Q-10. The G+C content of genomic DNA was 67.0 mol%. Comparisons with 16S rRNA gene sequences revealed that ZQBWT has the highest sequence similarities with members of the genus Tabrizicola (≤95.97 %), followed by Rhodobacter(≤95.96 %) and Falsirhodobacter(95.95 %) which all belong to the family Rhodobacteraceaein the phylum Proteobacteria. Photosynthesis genes pufLM were not found and photosynthesis pigments were not formed in ZQBWT. On the basis of the results from chemotaxonomic, phenotypic and phylogenetic analysis, ZQBWT represents a novel species of a novel genus, for which the name Xinfangfangia soli gen. nov., sp. nov. is proposed. The type strain is ZQBWT (=KCTC 62102T=CCTCC AB 2017177T).}, } @article {pmid29947476, year = {2018}, author = {Abe, G and Lee, SH and Li, IJ and Ota, KG}, title = {An alternative evolutionary pathway for the twin-tail goldfish via szl gene mutation.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {4}, pages = {234-241}, pmid = {29947476}, issn = {1552-5015}, abstract = {The twin-tail of ornamental goldfish provides unique evolutionary evidence that the highly conserved midline localization of axial skeleton components can be changed by artificial selection. This morphological change is known to be caused by a nonsense mutation in one of the recently duplicated chordin genes, which are key players in dorsal-ventral (DV) patterning. Since all of the multiple twin-tail ornamental goldfish strains share the same mutation, it is reasonable to presume that this mutation occurred only once in domesticated goldfish. However, zebrafish with mutated szl gene (another DV patterning-related gene) also exhibit twin-tail morphology and higher viability than dino/chordin-mutant zebrafish. This observation raises the question of whether the szl gene mutation could also reproduce the twin-tail morphology in goldfish. Here we show that goldfish have at least two subfunctionalized szl genes, designated szlA and szlB, and depletion of these genes in single-fin goldfish was able to reproduce the bifurcated caudal fin found in twin-tail ornamental goldfish. Interestingly, several phenotypes were observed in szlA-depleted fish, while low expressivity of the twin-tail phenotype was observed in szlB-depleted goldfish. Thus, even though szl gene mutations may produce twin-tail goldfish, these szl gene mutations might not be favorable for selection in domestic breeding. These results highlight the uniqueness and rarity of mutations that are able to cause large-scale morphological changes, such as a bifurcated axial skeleton, with high viability and expressivity in natural and domesticated populations.}, } @article {pmid29947421, year = {2018}, author = {Exposito-Alonso, M and Brennan, AC and Alonso-Blanco, C and Picó, FX}, title = {Spatio-temporal variation in fitness responses to contrasting environments in Arabidopsis thaliana.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13508}, pmid = {29947421}, issn = {1558-5646}, abstract = {The evolutionary response of organisms to global climate change is expected to be strongly conditioned by preexisting standing genetic variation. In addition, natural selection imposed by global climate change on fitness-related traits can be heterogeneous over time. We estimated selection of life-history traits of an entire genetic lineage of the plant Arabidopsis thaliana occurring in north-western Iberian Peninsula that were transplanted over multiple years into two environmentally contrasting field sites in southern Spain, as southern environments are expected to move progressively northwards with climate change in the Iberian Peninsula. The results indicated that natural selection on flowering time prevailed over that on recruitment. Selection favored early flowering in six of eight experiments and late flowering in the other two. Such heterogeneity of selection for flowering time might be a powerful mechanism for maintaining genetic diversity in the long run. We also found that north-western A. thaliana accessions from warmer environments exhibited higher fitness and higher phenotypic plasticity for flowering time in southern experimental facilities. Overall, our transplant experiments suggested that north-western Iberian A. thaliana has the means to cope with increasingly warmer environments in the region as predicted by trends in global climate change models.}, } @article {pmid29947081, year = {2018}, author = {Kranz, AM and Cole, GL and Singh, P and Endler, JA}, title = {Colour pattern component phenotypic divergence can be predicted by the light environment.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {10}, pages = {1459-1476}, doi = {10.1111/jeb.13342}, pmid = {29947081}, issn = {1420-9101}, support = {DP110101421//Australian Research Council/ ; DP150102817//Australian Research Council/ ; }, abstract = {The sensory drive hypothesis predicts that across different light environments sexually selected colour patterns will change to increase an animal's visual communication efficiency within different habitats. This is because individuals with more efficient signal components are likely to have more successful matings and hence produce more offspring. However, how colour pattern signals change over multiple generations under different light environmental conditions has not been tested experimentally. Here, we manipulated colour pattern signal efficiency by providing different ambient light environments over multiple generations to examine whether male colour pattern components change within large replicated populations of guppies (Poecilia reticulata). We report that colour patches change within populations over time and are phenotypically different among our three different light environments. Visual modelling suggests that the majority of these changes can be understood by considering the chroma, hue and luminance of each colour patch as seen by female guppies under each light environment. Taken together, our results support the hypothesis that different environmental conditions during signal reception can directly or indirectly drive the phenotypic diversification of visual signals within species.}, } @article {pmid29946896, year = {2018}, author = {Wang, Z and Tian, J and Li, X and Gan, L and He, L and Chu, Y and Tian, Y}, title = {Streptomyces dioscori sp. nov., a Novel Endophytic Actinobacterium Isolated from Bulbil of Dioscorea bulbifera L.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1384-1390}, pmid = {29946896}, issn = {1432-0991}, support = {2017YFB0308401//The National Key Research and Development Program of China/ ; 2016HM0100409SF//Chengdu Science and Technology Huimin Program/ ; }, mesh = {Base Composition ; DNA, Bacterial/genetics ; Dioscorea/*microbiology ; Endophytes/classification/genetics/*isolation & purification/metabolism ; Fatty Acids/chemistry/metabolism ; Flowers/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Streptomyces/classification/genetics/*isolation & purification/metabolism ; }, abstract = {A novel endophytic actinobacterium strain, A217T, was isolated from the bulbil of Dioscorea bulbifera L. Its taxonomic position was characterized using a polyphasic study. Morphological and chemotaxonomic characteristics of strain A217T were consistent with those of members of the genus Streptomyces: long straight to flexuous spore chain; cellular components contained LL-diaminopimelic acid, ribose, and small traces of glucose in whole-cell hydrolysates; MK-9(H6) and MK-9(H8) as predominant menaquinones. The patterns of major fatty acids are C16:0, anteiso-C15:0, C15:0, iso-C14:0, C16:1 ω7c, anteiso-C17:0, and iso-C17:1 ω5c. The polar lipids comprised diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylinositol mannoside, and glycolipid, as well as two unidentified phospholipids, one unidentified aminolipid, and one unidentified aminophospholipid. The DNA G + C content of draft genome is 70.7 mol%. Analysis of the 16S rRNA gene sequence and phylogenetic trees revealed that the isolate was most closely related to S. aurantiacus JCM 4453T (99.0%), S. glomeroaurantiacus JCM 4677T (99.0%), and S. tauricus JCM 4837T (98.8%). The DNA-DNA hybridization values between the strain A217T and three reference strains ranged from 34.6% to 51.7%. On the basis of phenotypic and genotypic differentiation from all tested strains, isolate A217T is proposed to represent a novel species of the genus Streptomyces, named Streptomyces dioscori sp. nov. The type strain is A217T (= CGMCC 4.7415T = JCM 32173T).}, } @article {pmid29946171, year = {2018}, author = {Slota, M and Keerthi, A and Myers, WK and Tretyakov, E and Baumgarten, M and Ardavan, A and Sadeghi, H and Lambert, CJ and Narita, A and Müllen, K and Bogani, L}, title = {Publisher Correction: Magnetic edge states and coherent manipulation of graphene nanoribbons.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {E31}, doi = {10.1038/s41586-018-0297-6}, pmid = {29946171}, issn = {1476-4687}, abstract = {In Fig. 1 of this Letter, there should have been two nitrogen (N) atoms at the 1,3-positions of all the blue chemical structures (next to the oxygen atoms), rather than one at the 2-position. The figure has been corrected online, and the original incorrect figure is shown as Supplementary Information to the accompanying Amendment.}, } @article {pmid29946170, year = {2018}, author = {Humphreys, PC and Kalb, N and Morits, JPJ and Schouten, RN and Vermeulen, RFL and Twitchen, DJ and Markham, M and Hanson, R}, title = {Publisher Correction: Deterministic delivery of remote entanglement on a quantum network.}, journal = {Nature}, volume = {562}, number = {7725}, pages = {E2}, doi = {10.1038/s41586-018-0314-9}, pmid = {29946170}, issn = {1476-4687}, abstract = {Change history: In this Letter, the received date should be 20 December 2017, instead of 27 April 2018. This has been corrected online.}, } @article {pmid29946169, year = {2018}, author = {Guerra, RE and Kelleher, CP and Hollingsworth, AD and Chaikin, PM}, title = {Addendum: Freezing on a sphere.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {E25}, doi = {10.1038/s41586-018-0233-9}, pmid = {29946169}, issn = {1476-4687}, } @article {pmid29946168, year = {2018}, author = {Shi, M and Lin, XD and Chen, X and Tian, JH and Chen, LJ and Li, K and Wang, W and Eden, JS and Shen, JJ and Liu, L and Holmes, EC and Zhang, YZ}, title = {Author Correction: The evolutionary history of vertebrate RNA viruses.}, journal = {Nature}, volume = {561}, number = {7722}, pages = {E6}, doi = {10.1038/s41586-018-0310-0}, pmid = {29946168}, issn = {1476-4687}, abstract = {Change history: In this Article, author Li Liu should be associated with affiliation number 5 (College of Marine Sciences, South China Agricultural University, Guangzhou, Guangdong, China), rather than affiliation number 4 (Wenzhou Center for Disease Control and Prevention, Wenzhou, Zhejiang, China). This has been corrected online.}, } @article {pmid29946165, year = {2018}, author = {Guo, J and Wilken, S and Jimenez, V and Choi, CJ and Ansong, C and Dannebaum, R and Sudek, L and Milner, DS and Bachy, C and Reistetter, EN and Elrod, VA and Klimov, D and Purvine, SO and Wei, CL and Kunde-Ramamoorthy, G and Richards, TA and Goodenough, U and Smith, RD and Callister, SJ and Worden, AZ}, title = {Specialized proteomic responses and an ancient photoprotection mechanism sustain marine green algal growth during phosphate limitation.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {781-790}, doi = {10.1038/s41564-018-0178-7}, pmid = {29946165}, issn = {2058-5276}, abstract = {Marine algae perform approximately half of global carbon fixation, but their growth is often limited by the availability of phosphate or other nutrients1,2. As oceans warm, the area of phosphate-limited surface waters is predicted to increase, resulting in ocean desertification3,4. Understanding the responses of key eukaryotic phytoplankton to nutrient limitation is therefore critical5,6. We used advanced photo-bioreactors to investigate how the widespread marine green alga Micromonas commoda grows under transitions from replete nutrients to chronic phosphate limitation and subsequent relief, analysing photosystem changes and broad cellular responses using proteomics, transcriptomics and biophysical measurements. We find that physiological and protein expression responses previously attributed to stress are critical to supporting stable exponential growth when phosphate is limiting. Unexpectedly, the abundance of most proteins involved in light harvesting does not change, but an ancient light-harvesting-related protein, LHCSR, is induced and dissipates damaging excess absorbed light as heat throughout phosphate limitation. Concurrently, a suite of uncharacterized proteins with narrow phylogenetic distributions increase multifold. Notably, of the proteins that exhibit significant changes, 70% are not differentially expressed at the mRNA transcript level, highlighting the importance of post-transcriptional processes in microbial eukaryotes. Nevertheless, transcript-protein pairs with concordant changes were identified that will enable more robust interpretation of eukaryotic phytoplankton responses in the field from metatranscriptomic studies. Our results show that P-limited Micromonas responds quickly to a fresh pulse of phosphate by rapidly increasing replication, and that the protein network associated with this ability is composed of both conserved and phylogenetically recent proteome systems that promote dynamic phosphate homeostasis. That an ancient mechanism for mitigating light stress is central to sustaining growth during extended phosphate limitation highlights the possibility of interactive effects arising from combined stressors under ocean change, which could reduce the efficacy of algal strategies for optimizing marine photosynthesis.}, } @article {pmid29946164, year = {2018}, author = {Rajeeve, K and Das, S and Prusty, BK and Rudel, T}, title = {Chlamydia trachomatis paralyses neutrophils to evade the host innate immune response.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {824-835}, doi = {10.1038/s41564-018-0182-y}, pmid = {29946164}, issn = {2058-5276}, abstract = {Chlamydia trachomatis, an obligate intracellular human pathogen, is a major cause of sexually transmitted diseases. Infections often occur without symptoms, a feature that has been attributed to the ability of the pathogen to evade the host immune response. We show here that C. trachomatis paralyses the host immune system by preventing the activation of polymorphic nuclear leukocytes (PMNs). PMNs infected with Chlamydia fail to produce neutrophil extracellular traps and the bacteria are able to survive in PMNs for extended periods of time. We have identified the secreted chlamydial protease-like activating factor (CPAF) as an effector mediating the evasion of the innate immune response since CPAF-deficient Chlamydia activate PMNs and are subsequently efficiently killed. CPAF suppresses the oxidative burst and interferes with chemical-mediated activation of neutrophils. We identified formyl peptide receptor 2 (FPR2) as a target of CPAF. FPR2 is cleaved by CPAF and released from the surface of PMNs. In contrast to previously described subversion mechanisms that mainly act on already activated PMNs, we describe here details of how Chlamydia actively paralyses PMNs, including the formation of neutrophil extracellular traps, to evade the host's innate immune response.}, } @article {pmid29946163, year = {2018}, author = {Heo, I and Dutta, D and Schaefer, DA and Iakobachvili, N and Artegiani, B and Sachs, N and Boonekamp, KE and Bowden, G and Hendrickx, APA and Willems, RJL and Peters, PJ and Riggs, MW and O'Connor, R and Clevers, H}, title = {Modelling Cryptosporidium infection in human small intestinal and lung organoids.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {814-823}, pmid = {29946163}, issn = {2058-5276}, support = {670133//European Research Council/International ; R21 AT009174/AT/NCCIH NIH HHS/United States ; }, abstract = {Stem-cell-derived organoids recapitulate in vivo physiology of their original tissues, representing valuable systems to model medical disorders such as infectious diseases. Cryptosporidium, a protozoan parasite, is a leading cause of diarrhoea and a major cause of child mortality worldwide. Drug development requires detailed knowledge of the pathophysiology of Cryptosporidium, but experimental approaches have been hindered by the lack of an optimal in vitro culture system. Here, we show that Cryptosporidium can infect epithelial organoids derived from human small intestine and lung. The parasite propagates within the organoids and completes its complex life cycle. Temporal analysis of the Cryptosporidium transcriptome during organoid infection reveals dynamic regulation of transcripts related to its life cycle. Our study presents organoids as a physiologically relevant in vitro model system to study Cryptosporidium infection.}, } @article {pmid29946162, year = {2018}, author = {Ma, L and Cordero, OX}, title = {Solving the structure-function puzzle.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {750-751}, doi = {10.1038/s41564-018-0186-7}, pmid = {29946162}, issn = {2058-5276}, } @article {pmid29946161, year = {2018}, author = {}, title = {Celebrate contributions great and small.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {749}, doi = {10.1038/s41564-018-0193-8}, pmid = {29946161}, issn = {2058-5276}, } @article {pmid29946124, year = {2018}, author = {Huisman, J and Codd, GA and Paerl, HW and Ibelings, BW and Verspagen, JMH and Visser, PM}, title = {Cyanobacterial blooms.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {8}, pages = {471-483}, doi = {10.1038/s41579-018-0040-1}, pmid = {29946124}, issn = {1740-1534}, abstract = {Cyanobacteria can form dense and sometimes toxic blooms in freshwater and marine environments, which threaten ecosystem functioning and degrade water quality for recreation, drinking water, fisheries and human health. Here, we review evidence indicating that cyanobacterial blooms are increasing in frequency, magnitude and duration globally. We highlight species traits and environmental conditions that enable cyanobacteria to thrive and explain why eutrophication and climate change catalyse the global expansion of cyanobacterial blooms. Finally, we discuss management strategies, including nutrient load reductions, changes in hydrodynamics and chemical and biological controls, that can help to prevent or mitigate the proliferation of cyanobacterial blooms.}, } @article {pmid29946123, year = {2018}, author = {Dart, A}, title = {Gut microbiota bile acid metabolism controls cancer immunosurveillance.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {8}, pages = {453}, doi = {10.1038/s41579-018-0053-9}, pmid = {29946123}, issn = {1740-1534}, } @article {pmid29946122, year = {2018}, author = {Du Toit, A}, title = {Falling into your own trap.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {8}, pages = {454-455}, doi = {10.1038/s41579-018-0054-8}, pmid = {29946122}, issn = {1740-1534}, } @article {pmid29946121, year = {2018}, author = {York, A}, title = {An aquatic origin of retroviruses.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {8}, pages = {455}, doi = {10.1038/s41579-018-0052-x}, pmid = {29946121}, issn = {1740-1534}, } @article {pmid29946100, year = {2018}, author = {Castelvecchi, D}, title = {Daring Japanese mission reaches unexplored asteroid Ryugu.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {495-496}, doi = {10.1038/d41586-018-05544-9}, pmid = {29946100}, issn = {1476-4687}, } @article {pmid29946099, year = {2018}, author = {}, title = {Worrying changes in Hungary.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {485}, doi = {10.1038/d41586-018-05526-x}, pmid = {29946099}, issn = {1476-4687}, mesh = {*Demography ; Financing, Organized ; Hungary ; *Politics ; Reward ; }, } @article {pmid29946098, year = {2018}, author = {Capper, MJ and Wacker, D}, title = {How the ubiquitous GPCR receptor family selectively activates signalling pathways.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {529-530}, doi = {10.1038/d41586-018-05503-4}, pmid = {29946098}, issn = {1476-4687}, mesh = {Receptors, G-Protein-Coupled ; *Receptors, Opioid ; *Signal Transduction ; }, } @article {pmid29946096, year = {2018}, author = {Elkins-Tanton, LT}, title = {Mars beat Earth in the race for habitable conditions.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {522-523}, doi = {10.1038/d41586-018-05496-0}, pmid = {29946096}, issn = {1476-4687}, mesh = {*Crystallization ; *Earth (Planet) ; Exobiology ; Extraterrestrial Environment ; Mars ; Oceans and Seas ; }, } @article {pmid29946095, year = {2018}, author = {Greber, T}, title = {Upstanding molecule reveals orbital wavefunction.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {525-526}, doi = {10.1038/d41586-018-05502-5}, pmid = {29946095}, issn = {1476-4687}, mesh = {*Electrons ; Models, Chemical ; *Quantum Theory ; }, } @article {pmid29946093, year = {2018}, author = {Silver, A}, title = {US-Chinese trade war puts scientists in the cross hairs.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {494-495}, doi = {10.1038/d41586-018-05521-2}, pmid = {29946093}, issn = {1476-4687}, mesh = {Chemistry/economics ; China ; Commerce/*economics ; International Cooperation/legislation & jurisprudence ; *Politics ; Research/*economics ; Research Personnel/*economics ; Taxes/*economics ; Technology/economics ; United States ; }, } @article {pmid29946092, year = {2018}, author = {Guglielmi, G}, title = {Methane leaks from US gas fields dwarf government estimates.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {496-497}, doi = {10.1038/d41586-018-05517-y}, pmid = {29946092}, issn = {1476-4687}, } @article {pmid29946090, year = {2018}, author = {Reardon, S}, title = {Genetically modified bacteria enlisted in fight against disease.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {497-498}, doi = {10.1038/d41586-018-05476-4}, pmid = {29946090}, issn = {1476-4687}, mesh = {Animals ; Bacteria/*genetics/*metabolism ; Bacteroides/genetics/metabolism ; Biological Therapy/adverse effects/*methods ; Clinical Trials as Topic ; Colitis/microbiology/therapy ; Escherichia coli/genetics/metabolism ; Gene Transfer, Horizontal/ethics ; HIV Infections/microbiology/prevention & control ; Humans ; Lactobacillus/genetics/metabolism ; Lactococcus lactis/genetics/metabolism ; Mice ; Phenylalanine/metabolism ; Phenylketonurias/microbiology/therapy ; }, } @article {pmid29946089, year = {2018}, author = {}, title = {Gene important in pregnancy shows evolution in action.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {488}, doi = {10.1038/d41586-018-05479-1}, pmid = {29946089}, issn = {1476-4687}, } @article {pmid29946088, year = {2018}, author = {}, title = {An eggshell mixture that sheds water and shrugs off punishment.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {489}, doi = {10.1038/d41586-018-05499-x}, pmid = {29946088}, issn = {1476-4687}, } @article {pmid29946087, year = {2018}, author = {}, title = {Ötzi the Iceman's tools tell a story of desperation.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {488}, doi = {10.1038/d41586-018-05497-z}, pmid = {29946087}, issn = {1476-4687}, } @article {pmid29946086, year = {2018}, author = {Cho, WKT}, title = {Algorithms can foster a more democratic society.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {487}, doi = {10.1038/d41586-018-05498-y}, pmid = {29946086}, issn = {1476-4687}, mesh = {*Algorithms ; *Democracy ; *Politics ; Supreme Court Decisions ; United States ; }, } @article {pmid29946085, year = {2018}, author = {}, title = {A short course of laxatives has long-lasting effects on microbiome.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {488-489}, doi = {10.1038/d41586-018-05480-8}, pmid = {29946085}, issn = {1476-4687}, } @article {pmid29946083, year = {2018}, author = {}, title = {Oaks last 800 years with help of DNA double take.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {489}, doi = {10.1038/d41586-018-05474-6}, pmid = {29946083}, issn = {1476-4687}, } @article {pmid29946082, year = {2018}, author = {}, title = {Puppies trust their mums - and humans.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {489}, doi = {10.1038/d41586-018-05478-2}, pmid = {29946082}, issn = {1476-4687}, } @article {pmid29946081, year = {2018}, author = {}, title = {A mini-laser that can light up living tissues.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {488}, doi = {10.1038/d41586-018-05470-w}, pmid = {29946081}, issn = {1476-4687}, } @article {pmid29946037, year = {2018}, author = {Wang, J and Lundberg, H and Asai, S and Martín-Acosta, P and Chen, JS and Brown, S and Farrell, W and Dushin, RG and O'Donnell, CJ and Ratnayake, AS and Richardson, P and Liu, Z and Qin, T and Blackmond, DG and Baran, PS}, title = {Kinetically guided radical-based synthesis of C(sp3)-C(sp3) linkages on DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6404-E6410}, pmid = {29946037}, issn = {1091-6490}, support = {R35 GM118176/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA/*chemistry ; *Gene Library ; Kinetics ; *Models, Molecular ; }, abstract = {DNA-encoded libraries (DEL)-based discovery platforms have recently been widely adopted in the pharmaceutical industry, mainly due to their powerful diversity and incredible number of molecules. In the two decades since their disclosure, great strides have been made to expand the toolbox of reaction modes that are compatible with the idiosyncratic aqueous, dilute, and DNA-sensitive parameters of this system. However, construction of highly important C(sp3)-C(sp3) linkages on DNA through cross-coupling remains unexplored. In this article, we describe a systematic approach to translating standard organic reactions to a DEL setting through the tactical combination of kinetic analysis and empirical screening with information captured from data mining. To exemplify this model, implementation of the Giese addition to forge high value C-C bonds on DNA was studied, which represents a radical-based synthesis in DEL.}, } @article {pmid29946036, year = {2018}, author = {Dahl-Halvarsson, M and Olive, M and Pokrzywa, M and Ejeskär, K and Palmer, RH and Uv, AE and Tajsharghi, H}, title = {Drosophila model of myosin myopathy rescued by overexpression of a TRIM-protein family member.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6566-E6575}, pmid = {29946036}, issn = {1091-6490}, mesh = {Animals ; Disease Models, Animal ; *Distal Myopathies/genetics/metabolism/pathology ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; *Genetic Loci ; Homozygote ; Humans ; *Mutation ; Myocardium/*metabolism/pathology ; *Myosin Heavy Chains/genetics/metabolism ; *Tripartite Motif Proteins/biosynthesis/genetics ; }, abstract = {Myosin is a molecular motor indispensable for body movement and heart contractility. Apart from pure cardiomyopathy, mutations in MYH7 encoding slow/β-cardiac myosin heavy chain also cause skeletal muscle disease with or without cardiac involvement. Mutations within the α-helical rod domain of MYH7 are mainly associated with Laing distal myopathy. To investigate the mechanisms underlying the pathology of the recurrent causative MYH7 mutation (K1729del), we have developed a Drosophila melanogaster model of Laing distal myopathy by genomic engineering of the Drosophila Mhc locus. Homozygous MhcK1728del animals die during larval/pupal stages, and both homozygous and heterozygous larvae display reduced muscle function. Flies expressing only MhcK1728del in indirect flight and jump muscles, and heterozygous MhcK1728del animals, were flightless, with reduced movement and decreased lifespan. Sarcomeres of MhcK1728del mutant indirect flight muscles and larval body wall muscles were disrupted with clearly disorganized muscle filaments. Homozygous MhcK1728del larvae also demonstrated structural and functional impairments in heart muscle, which were not observed in heterozygous animals, indicating a dose-dependent effect of the mutated allele. The impaired jump and flight ability and the myopathy of indirect flight and leg muscles associated with MhcK1728del were fully suppressed by expression of Abba/Thin, an E3-ligase that is essential for maintaining sarcomere integrity. This model of Laing distal myopathy in Drosophila recapitulates certain morphological phenotypic features seen in Laing distal myopathy patients with the recurrent K1729del mutation. Our observations that Abba/Thin modulates these phenotypes suggest that manipulation of Abba/Thin activity levels may be beneficial in Laing distal myopathy.}, } @article {pmid29946035, year = {2018}, author = {Archer, NM and Petersen, N and Clark, MA and Buckee, CO and Childs, LM and Duraisingh, MT}, title = {Resistance to Plasmodium falciparum in sickle cell trait erythrocytes is driven by oxygen-dependent growth inhibition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7350-7355}, pmid = {29946035}, issn = {1091-6490}, support = {K12 HL087164/HL/NHLBI NIH HHS/United States ; R01 HL139337/HL/NHLBI NIH HHS/United States ; }, mesh = {Antisickling Agents/pharmacology ; Carbon Monoxide/pharmacology ; *DNA Replication ; DNA, Protozoan/*biosynthesis ; Erythrocytes, Abnormal/*metabolism/parasitology ; Humans ; Malaria, Falciparum/metabolism ; Oxygen/*metabolism ; Plasmodium falciparum/*metabolism ; Sickle Cell Trait/*metabolism/parasitology ; }, abstract = {Sickle cell trait (AS) confers partial protection against lethal Plasmodium falciparum malaria. Multiple mechanisms for this have been proposed, with a recent focus on aberrant cytoadherence of parasite-infected red blood cells (RBCs). Here we investigate the mechanistic basis of AS protection through detailed temporal mapping. We find that parasites in AS RBCs maintained at low oxygen concentrations stall at a specific stage in the middle of intracellular growth before DNA replication. We demonstrate that polymerization of sickle hemoglobin (HbS) is responsible for this growth arrest of intraerythrocytic P. falciparum parasites, with normal hemoglobin digestion and growth restored in the presence of carbon monoxide, a gaseous antisickling agent. Modeling of growth inhibition and sequestration revealed that HbS polymerization-induced growth inhibition following cytoadherence is the critical driver of the reduced parasite densities observed in malaria infections of individuals with AS. We conclude that the protective effect of AS derives largely from effective sequestration of infected RBCs into the hypoxic microcirculation.}, } @article {pmid29946034, year = {2018}, author = {Chamberland, S and Timofeeva, Y and Evstratova, A and Volynski, K and Tóth, K}, title = {Action potential counting at giant mossy fiber terminals gates information transfer in the hippocampus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7434-7439}, pmid = {29946034}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MR/M013812/1//Medical Research Council/United Kingdom ; MOP-81142//CIHR/Canada ; }, mesh = {Action Potentials/*physiology ; Animals ; CA3 Region, Hippocampal/cytology/*physiology ; Calcium/metabolism ; Calcium Signaling/*physiology ; Male ; *Models, Neurological ; Mossy Fibers, Hippocampal/*physiology ; Presynaptic Terminals/physiology ; Pyramidal Cells/cytology/*physiology ; Rats ; }, abstract = {Neuronal communication relies on action potential discharge, with the frequency and the temporal precision of action potentials encoding information. Hippocampal mossy fibers have long been recognized as conditional detonators owing to prominent short-term facilitation of glutamate release displayed during granule cell burst firing. However, the spiking patterns required to trigger action potential firing in CA3 pyramidal neurons remain poorly understood. Here, we show that glutamate release from mossy fiber terminals triggers action potential firing of the target CA3 pyramidal neurons independently of the average granule cell burst frequency, a phenomenon we term action potential counting. We find that action potential counting in mossy fibers gates glutamate release over a broad physiological range of frequencies and action potential numbers. Using rapid Ca2+ imaging we also show that the magnitude of evoked Ca2+ influx stays constant during action potential trains and that accumulated residual Ca2+ is gradually extruded on a time scale of several hundred milliseconds. Using experimentally constrained 3D model of presynaptic Ca2+ influx, buffering, and diffusion, and a Monte Carlo model of Ca2+-activated vesicle fusion, we argue that action potential counting at mossy fiber boutons can be explained by a unique interplay between Ca2+ dynamics and buffering at release sites. This is largely determined by the differential contribution of major endogenous Ca2+ buffers calbindin-D28K and calmodulin and by the loose coupling between presynaptic voltage-gated Ca2+ channels and release sensors and the relatively slow Ca2+ extrusion rate. Taken together, our results identify a previously unexplored information-coding mechanism in the brain.}, } @article {pmid29946033, year = {2018}, author = {Lewis, RD and Garcia-Borràs, M and Chalkley, MJ and Buller, AR and Houk, KN and Kan, SBJ and Arnold, FH}, title = {Catalytic iron-carbene intermediate revealed in a cytochrome c carbene transferase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7308-7313}, pmid = {29946033}, issn = {1091-6490}, support = {T32 GM007616/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; *Directed Molecular Evolution ; Methane/*analogs & derivatives/chemistry/metabolism ; Porphyrins/*chemistry/genetics/metabolism ; Rhodothermus/*enzymology/genetics ; Transferases/*chemistry/genetics/metabolism ; }, abstract = {Recently, heme proteins have been discovered and engineered by directed evolution to catalyze chemical transformations that are biochemically unprecedented. Many of these nonnatural enzyme-catalyzed reactions are assumed to proceed through a catalytic iron porphyrin carbene (IPC) intermediate, although this intermediate has never been observed in a protein. Using crystallographic, spectroscopic, and computational methods, we have captured and studied a catalytic IPC intermediate in the active site of an enzyme derived from thermostable Rhodothermus marinus (Rma) cytochrome c High-resolution crystal structures and computational methods reveal how directed evolution created an active site for carbene transfer in an electron transfer protein and how the laboratory-evolved enzyme achieves perfect carbene transfer stereoselectivity by holding the catalytic IPC in a single orientation. We also discovered that the IPC in Rma cytochrome c has a singlet ground electronic state and that the protein environment uses geometrical constraints and noncovalent interactions to influence different IPC electronic states. This information helps us to understand the impressive reactivity and selectivity of carbene transfer enzymes and offers insights that will guide and inspire future engineering efforts.}, } @article {pmid29946032, year = {2018}, author = {Yang, M and Yan, D and Yuan, F and Jiang, P and Ma, E and Wu, X}, title = {Dynamically reinforced heterogeneous grain structure prolongs ductility in a medium-entropy alloy with gigapascal yield strength.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7224-7229}, pmid = {29946032}, issn = {1091-6490}, abstract = {Ductility, i.e., uniform strain achievable in uniaxial tension, diminishes for materials with very high yield strength. Even for the CrCoNi medium-entropy alloy (MEA), which has a simple face-centered cubic (FCC) structure that would bode well for high ductility, the fine grains processed to achieve gigapascal strength exhaust the strain hardening ability such that, after yielding, the uniform tensile strain is as low as ∼2%. Here we purposely deploy, in this MEA, a three-level heterogeneous grain structure (HGS) with grain sizes spanning the nanometer to micrometer range, imparting a high yield strength well in excess of 1 GPa. This heterogeneity results from this alloy's low stacking fault energy, which facilitates corner twins in recrystallization and stores deformation twins and stacking faults during tensile straining. After yielding, the elastoplastic transition through load transfer and strain partitioning among grains of different sizes leads to an upturn of the strain hardening rate, and, upon further tensile straining at room temperature, corner twins evolve into nanograins. This dynamically reinforced HGS leads to a sustainable strain hardening rate, a record-wide hysteresis loop in load-unload-reload stress-strain curve and hence high back stresses, and, consequently, a uniform tensile strain of 22%. As such, this HGS achieves, in a single-phase FCC alloy, a strength-ductility combination that would normally require heterogeneous microstructures such as in dual-phase steels.}, } @article {pmid29946031, year = {2018}, author = {Vora, A and Zhou, W and Londono-Renteria, B and Woodson, M and Sherman, MB and Colpitts, TM and Neelakanta, G and Sultana, H}, title = {Arthropod EVs mediate dengue virus transmission through interaction with a tetraspanin domain containing glycoprotein Tsp29Fb.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6604-E6613}, pmid = {29946031}, issn = {1091-6490}, mesh = {Aedes ; Animals ; Cell Line ; *Dengue/genetics/metabolism/transmission ; *Dengue Virus/genetics/metabolism/pathogenicity ; *Extracellular Vesicles/genetics/metabolism/virology ; Human Umbilical Vein Endothelial Cells ; Humans ; *Insect Proteins/genetics/metabolism ; Mice ; Protein Domains ; *Viral Envelope Proteins/genetics/metabolism ; }, abstract = {Dengue virus (DENV) is a mosquito-borne flavivirus that causes dengue fever in humans, worldwide. Using in vitro cell lines derived from Aedes albopictus and Aedes aegypti, the primary vectors of DENV, we report that DENV2/DENV3-infected cells secrete extracellular vesicles (EVs), including exosomes, containing infectious viral RNA and proteins. A full-length DENV2 genome, detected in arthropod EVs, was infectious to naïve mosquito and mammalian cells, including human-skin keratinocytes and blood endothelial cells. Cryo-electron microscopy showed mosquito EVs with a size range from 30 to 250 nm. Treatments with RNase A, Triton X-100, and 4G2 antibody-bead binding assays showed that infectious DENV2-RNA and proteins are contained inside EVs. Viral plaque formation and dilution assays also showed securely contained infectious viral RNA and proteins in EVs are transmitted to human cells. Up-regulated HSP70 upon DENV2 infection showed no role in viral replication and transmission through EVs. In addition, qRT-PCR and immunoblotting results revealed that DENV2 up-regulates expression of a mosquito tetraspanin-domain-containing glycoprotein, designated as Tsp29Fb, in A. aegypti mosquitoes, cells, and EVs. RNAi-mediated silencing and antibody blocking of Tsp29Fb resulted in reduced DENV2 loads in both mosquito cells and EVs. Immunoprecipitation showed Tsp29Fb to directly interact with DENV2 E-protein. Furthermore, treatment with GW4869 (exosome-release inhibitor) affected viral burden, direct interaction of Tsp29Fb with E-protein and EV-mediated transmission of viral RNA and proteins to naïve human cells. In summary, we report a very important finding on EV-mediated transmission of DENV2 from arthropod to mammalian cells through interactions with an arthropod EVs-enriched marker Tsp29Fb.}, } @article {pmid29946030, year = {2018}, author = {Tarakanova, A and Yeo, GC and Baldock, C and Weiss, AS and Buehler, MJ}, title = {Molecular model of human tropoelastin and implications of associated mutations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7338-7343}, pmid = {29946030}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 088785/Z/09/Z//Wellcome Trust/United Kingdom ; BB/N015398/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Humans ; *Molecular Dynamics Simulation ; *Mutation ; Tropoelastin/*chemistry/genetics/metabolism ; }, abstract = {Protein folding poses unique challenges for large, disordered proteins due to the low resolution of structural data accessible in experiment and on the basis of short time scales and limited sampling attainable in computation. Such molecules are uniquely suited to accelerated-sampling molecular dynamics algorithms due to a flat-energy landscape. We apply these methods to report here the folded structure in water from a fully extended chain of tropoelastin, a 698-amino acid molecular precursor to elastic fibers that confer elasticity and recoil to tissues, finding good agreement with experimental data. We then study a series of artificial and disease-related mutations, yielding molecular mechanisms to explain structural differences and variation in hierarchical assembly observed in experiment. The present model builds a framework for studying assembly and disease and yields critical insight into molecular mechanisms behind these processes. These results suggest that proteins with disordered regions are suitable candidates for characterization by this approach.}, } @article {pmid29946029, year = {2018}, author = {Lincoln, V and Cogan, J and Hou, Y and Hirsch, M and Hao, M and Alexeev, V and De Luca, M and De Rosa, L and Bauer, JW and Woodley, DT and Chen, M}, title = {Gentamicin induces LAMB3 nonsense mutation readthrough and restores functional laminin 332 in junctional epidermolysis bullosa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6536-E6545}, pmid = {29946029}, issn = {1091-6490}, mesh = {*Cell Adhesion Molecules/genetics/metabolism ; *Codon, Nonsense ; *Epidermolysis Bullosa, Junctional/genetics/metabolism/pathology ; Gentamicins/*pharmacology ; HEK293 Cells ; Humans ; Integrin alpha6beta4/genetics/metabolism ; Keratinocytes/*metabolism/pathology ; Mutagenesis/*drug effects ; }, abstract = {Herlitz junctional epidermolysis bullosa (H-JEB) is an incurable, devastating, and mostly fatal inherited skin disease for which there is only supportive care. H-JEB is caused by loss-of-function mutations in LAMA3, LAMB3, or LAMC2, leading to complete loss of laminin 332, the major component of anchoring filaments, which mediate epidermal-dermal adherence. LAMB3 (laminin β3) mutations account for 80% of patients with H-JEB, and ∼95% of H-JEB-associated LAMB3 mutations are nonsense mutations leading to premature termination codons (PTCs). In this study, we evaluated the ability of gentamicin to induce PTC readthrough in H-JEB laminin β3-null keratinocytes transfected with expression vectors encoding eight different LAMB3 nonsense mutations. We found that gentamicin induced PTC readthrough in all eight nonsense mutations tested. We next used lentiviral vectors to generate stably transduced H-JEB cells with the R635X and C290X nonsense mutations. Incubation of these cell lines with various concentrations of gentamicin resulted in the synthesis and secretion of full-length laminin β3 in a dose-dependent and sustained manner. Importantly, the gentamicin-induced laminin β3 led to the restoration of laminin 332 assembly, secretion, and deposition within the dermal/epidermal junction, as well as proper polarization of α6β4 integrin in basal keratinocytes, as assessed by immunoblot analysis, immunofluorescent microscopy, and an in vitro 3D skin equivalent model. Finally, newly restored laminin 332 corrected the abnormal cellular phenotype of H-JEB cells by reversing abnormal cell morphology, poor growth potential, poor cell-substratum adhesion, and hypermotility. Therefore, gentamicin may offer a therapy for H-JEB and other inherited skin diseases caused by PTC mutations.}, } @article {pmid29946028, year = {2018}, author = {Prasad, H and Rao, R}, title = {Amyloid clearance defect in ApoE4 astrocytes is reversed by epigenetic correction of endosomal pH.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6640-E6649}, pmid = {29946028}, issn = {1091-6490}, support = {R01 DK054214/DK/NIDDK NIH HHS/United States ; }, mesh = {Alzheimer Disease/drug therapy/genetics/metabolism/pathology ; Amyloid beta-Peptides/genetics/*metabolism ; Animals ; Apolipoprotein E4/genetics/*metabolism ; Astrocytes/*metabolism/pathology ; Ataxia/drug therapy/genetics/metabolism/pathology ; Endosomes/genetics/*metabolism/pathology ; *Epigenesis, Genetic ; Epilepsy/drug therapy/genetics/metabolism/pathology ; Genetic Diseases, X-Linked/drug therapy/genetics/metabolism/pathology ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/genetics/metabolism ; Humans ; Hydrogen-Ion Concentration ; Intellectual Disability/drug therapy/genetics/metabolism/pathology ; Mice ; Mice, Knockout ; Microcephaly/drug therapy/genetics/metabolism/pathology ; Ocular Motility Disorders/drug therapy/genetics/metabolism/pathology ; Receptors, LDL/genetics/metabolism ; Sodium-Hydrogen Exchangers/genetics/metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; }, abstract = {Endosomes have emerged as a central hub and pathogenic driver of Alzheimer's disease (AD). The earliest brain cytopathology in neurodegeneration, occurring decades before amyloid plaques and cognitive decline, is an expansion in the size and number of endosomal compartments. The strongest genetic risk factor for sporadic AD is the ε4 allele of Apolipoprotein E (ApoE4). Previous studies have shown that ApoE4 potentiates presymptomatic endosomal dysfunction and defective endocytic clearance of amyloid beta (Aβ), although how these two pathways are linked at a cellular and mechanistic level has been unclear. Here, we show that aberrant endosomal acidification in ApoE4 astrocytes traps the low-density lipoprotein receptor-related protein (LRP1) within intracellular compartments, leading to loss of surface expression and Aβ clearance. Pathological endosome acidification is caused by ε4 risk allele-selective down-regulation of the Na+/H+ exchanger isoform NHE6, which functions as a critical leak pathway for endosomal protons. In vivo, the NHE6 knockout (NHE6KO) mouse model showed elevated Aβ in the brain, consistent with a causal effect. Increased nuclear translocation of histone deacetylase 4 (HDAC4) in ApoE4 astrocytes, compared with the nonpathogenic ApoE3 allele, suggested a mechanistic basis for transcriptional down-regulation of NHE6. HDAC inhibitors that restored NHE6 expression normalized ApoE4-specific defects in endosomal pH, LRP1 trafficking, and amyloid clearance. Thus, NHE6 is a downstream effector of ApoE4 and emerges as a promising therapeutic target in AD. These observations have prognostic implications for patients who have Christianson syndrome with loss of function mutations in NHE6 and exhibit prominent glial pathology and progressive hallmarks of neurodegeneration.}, } @article {pmid29946027, year = {2018}, author = {Eichhorn, CD and Yang, Y and Repeta, L and Feigon, J}, title = {Structural basis for recognition of human 7SK long noncoding RNA by the La-related protein Larp7.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6457-E6466}, pmid = {29946027}, issn = {1091-6490}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; P41 RR015301/RR/NCRR NIH HHS/United States ; R25 GM055052/GM/NIGMS NIH HHS/United States ; S10 OD016336/OD/NIH HHS/United States ; RRP 14-179/HX/HSRD VA/United States ; R01 GM107567/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Crystallography, X-Ray ; Humans ; *Models, Molecular ; RNA, Long Noncoding/*chemistry ; Ribonucleoproteins/*chemistry ; }, abstract = {The La and the La-related protein (LARP) superfamily is a diverse class of RNA binding proteins involved in RNA processing, folding, and function. Larp7 binds to the abundant long noncoding 7SK RNA and is required for 7SK ribonucleoprotein (RNP) assembly and function. The 7SK RNP sequesters a pool of the positive transcription elongation factor b (P-TEFb) in an inactive state; on release, P-TEFb phosphorylates RNA Polymerase II to stimulate transcription elongation. Despite its essential role in transcription, limited structural information is available for the 7SK RNP, particularly for protein-RNA interactions. Larp7 contains an N-terminal La module that binds UUU-3'OH and a C-terminal atypical RNA recognition motif (xRRM) required for specific binding to 7SK and P-TEFb assembly. Deletion of the xRRM is linked to gastric cancer in humans. We report the 2.2-Å X-ray crystal structure of the human La-related protein group 7 (hLarp7) xRRM bound to the 7SK stem-loop 4, revealing a unique binding interface. Contributions of observed interactions to binding affinity were investigated by mutagenesis and isothermal titration calorimetry. NMR 13C spin relaxation data and comparison of free xRRM, RNA, and xRRM-RNA structures show that the xRRM is preordered to bind a flexible loop 4. Combining structures of the hLarp7 La module and the xRRM-7SK complex presented here, we propose a structural model for Larp7 binding to the 7SK 3' end and mechanism for 7SK RNP assembly. This work provides insight into how this domain contributes to 7SK recognition and assembly of the core 7SK RNP.}, } @article {pmid29946026, year = {2018}, author = {Bunnefeld, L and Hearn, J and Stone, GN and Lohse, K}, title = {Whole-genome data reveal the complex history of a diverse ecological community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6507-E6515}, pmid = {29946026}, issn = {1091-6490}, mesh = {*Ecosystem ; *Metagenome ; *Models, Biological ; }, abstract = {How widespread ecological communities assemble remains a key question in ecology. Trophic interactions between widespread species may reflect a shared population history or ecological fitting of local pools of species with very different population histories. Which scenario applies is central to the stability of trophic associations and the potential for coevolution between species. Here we show how alternative community assembly hypotheses can be discriminated using whole-genome data for component species and provide a likelihood framework that overcomes current limitations in formal comparison of multispecies histories. We illustrate our approach by inferring the assembly history of a Western Palearctic community of insect herbivores and parasitoid natural enemies, trophic groups that together comprise 50% of terrestrial species. We reject models of codispersal from a shared origin and of delayed enemy pursuit of their herbivore hosts, arguing against herbivore attainment of "enemy-free space." The community-wide distribution of species expansion times is also incompatible with a random, neutral model of assembly. Instead, we reveal a complex assembly history of single- and multispecies range expansions through the Pleistocene from different directions and over a range of timescales. Our results suggest substantial turnover in species associations and argue against tight coevolution in this system. The approach we illustrate is widely applicable to natural communities of nonmodel species and makes it possible to reveal the historical backdrop against which natural selection acts.}, } @article {pmid29946025, year = {2018}, author = {Harris, DN and Song, W and Shetty, AC and Levano, KS and Cáceres, O and Padilla, C and Borda, V and Tarazona, D and Trujillo, O and Sanchez, C and Kessler, MD and Galarza, M and Capristano, S and Montejo, H and Flores-Villanueva, PO and Tarazona-Santos, E and O'Connor, TD and Guio, H}, title = {Evolutionary genomic dynamics of Peruvians before, during, and after the Inca Empire.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6526-E6535}, pmid = {29946025}, issn = {1091-6490}, mesh = {History, Ancient ; Humans ; Indians, South American/*genetics/history ; *Models, Genetic ; Peru ; *Population Dynamics ; }, abstract = {Native Americans from the Amazon, Andes, and coastal geographic regions of South America have a rich cultural heritage but are genetically understudied, therefore leading to gaps in our knowledge of their genomic architecture and demographic history. In this study, we sequence 150 genomes to high coverage combined with an additional 130 genotype array samples from Native American and mestizo populations in Peru. The majority of our samples possess greater than 90% Native American ancestry, which makes this the most extensive Native American sequencing project to date. Demographic modeling reveals that the peopling of Peru began ∼12,000 y ago, consistent with the hypothesis of the rapid peopling of the Americas and Peruvian archeological data. We find that the Native American populations possess distinct ancestral divisions, whereas the mestizo groups were admixtures of multiple Native American communities that occurred before and during the Inca Empire and Spanish rule. In addition, the mestizo communities also show Spanish introgression largely following Peruvian Independence, nearly 300 y after Spain conquered Peru. Further, we estimate migration events between Peruvian populations from all three geographic regions with the majority of between-region migration moving from the high Andes to the low-altitude Amazon and coast. As such, we present a detailed model of the evolutionary dynamics which impacted the genomes of modern-day Peruvians and a Native American ancestry dataset that will serve as a beneficial resource to addressing the underrepresentation of Native American ancestry in sequencing studies.}, } @article {pmid29946024, year = {2018}, author = {Raznahan, A and Parikshak, NN and Chandran, V and Blumenthal, JD and Clasen, LS and Alexander-Bloch, AF and Zinn, AR and Wangsa, D and Wise, J and Murphy, DGM and Bolton, PF and Ried, T and Ross, J and Giedd, JN and Geschwind, DH}, title = {Sex-chromosome dosage effects on gene expression in humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7398-7403}, pmid = {29946024}, issn = {1091-6490}, mesh = {*Aneuploidy ; Animals ; *Chromosomes, Human, X/genetics/metabolism ; *Chromosomes, Human, Y/genetics/metabolism ; Female ; *Gene Dosage ; *Gene Expression Regulation ; Genome-Wide Association Study ; Humans ; *Kruppel-Like Transcription Factors/genetics/metabolism ; Male ; Mice ; Mice, Knockout ; *Models, Genetic ; }, abstract = {A fundamental question in the biology of sex differences has eluded direct study in humans: How does sex-chromosome dosage (SCD) shape genome function? To address this, we developed a systematic map of SCD effects on gene function by analyzing genome-wide expression data in humans with diverse sex-chromosome aneuploidies (XO, XXX, XXY, XYY, and XXYY). For sex chromosomes, we demonstrate a pattern of obligate dosage sensitivity among evolutionarily preserved X-Y homologs and update prevailing theoretical models for SCD compensation by detecting X-linked genes that increase expression with decreasing X- and/or Y-chromosome dosage. We further show that SCD-sensitive sex-chromosome genes regulate specific coexpression networks of SCD-sensitive autosomal genes with critical cellular functions and a demonstrable potential to mediate previously documented SCD effects on disease. These gene coexpression results converge with analysis of transcription factor binding site enrichment and measures of gene expression in murine knockout models to spotlight the dosage-sensitive X-linked transcription factor ZFX as a key mediator of SCD effects on wider genome expression. Our findings characterize the effects of SCD broadly across the genome, with potential implications for human phenotypic variation.}, } @article {pmid29946023, year = {2018}, author = {Zhou, Q and Tang, P and Liu, S and Pan, J and Yan, Q and Zhang, SC}, title = {Learning atoms for materials discovery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6411-E6417}, pmid = {29946023}, issn = {1091-6490}, abstract = {Exciting advances have been made in artificial intelligence (AI) during recent decades. Among them, applications of machine learning (ML) and deep learning techniques brought human-competitive performances in various tasks of fields, including image recognition, speech recognition, and natural language understanding. Even in Go, the ancient game of profound complexity, the AI player has already beat human world champions convincingly with and without learning from the human. In this work, we show that our unsupervised machines (Atom2Vec) can learn the basic properties of atoms by themselves from the extensive database of known compounds and materials. These learned properties are represented in terms of high-dimensional vectors, and clustering of atoms in vector space classifies them into meaningful groups consistent with human knowledge. We use the atom vectors as basic input units for neural networks and other ML models designed and trained to predict materials properties, which demonstrate significant accuracy.}, } @article {pmid29946022, year = {2018}, author = {Van Houten, B and Kad, NM}, title = {Single-cell mutagenic responses and cell death revealed in real time.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7168-7170}, pmid = {29946022}, issn = {1091-6490}, support = {R01 ES019566/ES/NIEHS NIH HHS/United States ; }, mesh = {Cell Death ; *Mutagenesis ; Mutagenicity Tests ; *Mutagens ; Salmonella typhimurium/genetics ; }, } @article {pmid29946021, year = {2018}, author = {Remington, BA and Park, HS and Casey, DT and Cavallo, RM and Clark, DS and Huntington, CM and Kuranz, CC and Miles, AR and Nagel, SR and Raman, KS and Smalyuk, VA}, title = {Rayleigh-Taylor instabilities in high-energy density settings on the National Ignition Facility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1717236115}, pmid = {29946021}, issn = {1091-6490}, abstract = {The Rayleigh-Taylor (RT) instability occurs at an interface between two fluids of differing density during an acceleration. These instabilities can occur in very diverse settings, from inertial confinement fusion (ICF) implosions over spatial scales of [Formula: see text] cm (10-1,000 μm) to supernova explosions at spatial scales of [Formula: see text] cm and larger. We describe experiments and techniques for reducing ("stabilizing") RT growth in high-energy density (HED) settings on the National Ignition Facility (NIF) at Lawrence Livermore National Laboratory. Three unique regimes of stabilization are described: (i) at an ablation front, (ii) behind a radiative shock, and (iii) due to material strength. For comparison, we also show results from nonstabilized "classical" RT instability evolution in HED regimes on the NIF. Examples from experiments on the NIF in each regime are given. These phenomena also occur in several astrophysical scenarios and planetary science [Drake R (2005) Plasma Phys Controlled Fusion 47:B419-B440; Dahl TW, Stevenson DJ (2010) Earth Planet Sci Lett 295:177-186].}, } @article {pmid29946020, year = {2018}, author = {Wang, J and Huang, M and Torre, E and Dueck, H and Shaffer, S and Murray, J and Raj, A and Li, M and Zhang, NR}, title = {Gene expression distribution deconvolution in single-cell RNA sequencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6437-E6446}, pmid = {29946020}, issn = {1091-6490}, support = {R01 HG006137/HG/NHGRI NIH HHS/United States ; R01 GM125301/GM/NIGMS NIH HHS/United States ; R01 GM108600/GM/NIGMS NIH HHS/United States ; R01 HL113147/HL/NHLBI NIH HHS/United States ; R21 HD085201/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Gene Expression Regulation ; *High-Throughput Nucleotide Sequencing ; Humans ; *Models, Genetic ; RNA/*biosynthesis/*genetics ; }, abstract = {Single-cell RNA sequencing (scRNA-seq) enables the quantification of each gene's expression distribution across cells, thus allowing the assessment of the dispersion, nonzero fraction, and other aspects of its distribution beyond the mean. These statistical characterizations of the gene expression distribution are critical for understanding expression variation and for selecting marker genes for population heterogeneity. However, scRNA-seq data are noisy, with each cell typically sequenced at low coverage, thus making it difficult to infer properties of the gene expression distribution from raw counts. Based on a reexamination of nine public datasets, we propose a simple technical noise model for scRNA-seq data with unique molecular identifiers (UMI). We develop deconvolution of single-cell expression distribution (DESCEND), a method that deconvolves the true cross-cell gene expression distribution from observed scRNA-seq counts, leading to improved estimates of properties of the distribution such as dispersion and nonzero fraction. DESCEND can adjust for cell-level covariates such as cell size, cell cycle, and batch effects. DESCEND's noise model and estimation accuracy are further evaluated through comparisons to RNA FISH data, through data splitting and simulations and through its effectiveness in removing known batch effects. We demonstrate how DESCEND can clarify and improve downstream analyses such as finding differentially expressed genes, identifying cell types, and selecting differentiation markers.}, } @article {pmid29945979, year = {2018}, author = {Beans, C}, title = {Inner Workings: The race to patch the human heart.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6518-6520}, pmid = {29945979}, issn = {1091-6490}, mesh = {Animals ; Cells, Cultured ; Cellular Reprogramming Techniques ; Clinical Trials as Topic ; Embryonic Stem Cells/transplantation ; Heart Conduction System/physiopathology ; Heart Rate ; Humans ; Induced Pluripotent Stem Cells/transplantation ; Mice ; Muscle Cells/transplantation ; Myocardial Contraction ; Myocardial Infarction/*therapy ; Myocytes, Cardiac/*transplantation ; Printing, Three-Dimensional ; Rats ; Spheroids, Cellular/cytology ; Swine ; Tissue Scaffolds ; }, } @article {pmid29945978, year = {2018}, author = {Ornes, S}, title = {Science and Culture: Math tools send legislators back to the drawing board.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6515-6517}, pmid = {29945978}, issn = {1091-6490}, } @article {pmid29945759, year = {2018}, author = {Reece, SE and Schneider, P}, title = {Premature Rejection of Plasticity in Conversion.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {633-634}, doi = {10.1016/j.pt.2018.06.004}, pmid = {29945759}, issn = {1471-5007}, mesh = {Humans ; *Malaria, Falciparum ; *Plasmodium falciparum ; }, } @article {pmid29945721, year = {2018}, author = {Barshad, G and Marom, S and Cohen, T and Mishmar, D}, title = {Mitochondrial DNA Transcription and Its Regulation: An Evolutionary Perspective.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {9}, pages = {682-692}, doi = {10.1016/j.tig.2018.05.009}, pmid = {29945721}, issn = {0168-9525}, abstract = {The bacterial heritage of mitochondria, as well as its independent genome [mitochondrial DNA (mtDNA)] and polycistronic transcripts, led to the view that mitochondrial transcriptional regulation relies on an evolutionarily conserved, prokaryotic-like system that is separated from the rest of the cell. Indeed, mtDNA transcription was previously thought to be governed by a few dedicated direct regulators, namely, the mitochondrial RNA polymerase (POLRMT), two transcription factors (TFAM and TF2BM), one transcription elongation (TEFM), and one known transcription termination factor (mTERF1). Recent findings have, however, revealed that known nuclear gene expression regulators are also involved in mtDNA transcription and have identified novel transcriptional features consistent with adaptation of the mitochondria to the regulatory environment of the precursor of the eukaryotic cell. Finally, whereas mammals follow the human mtDNA transcription pattern, other organisms notably diverge in terms of mtDNA transcriptional regulation. Hence, mtDNA transcriptional regulation is likely more evolutionary diverse than once thought.}, } @article {pmid29945676, year = {2018}, author = {Sathananthasarma, P and Weeratunga, PN and Chang, T}, title = {Reversible splenial lesion syndrome associated with dengue fever: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {412}, pmid = {29945676}, issn = {1756-0500}, mesh = {Adult ; Brain Diseases/*etiology ; Corpus Callosum/diagnostic imaging/*pathology ; Dengue/*complications ; Encephalitis ; Humans ; Magnetic Resonance Imaging ; Male ; Sri Lanka ; Young Adult ; }, abstract = {BACKGROUND: Dengue virus infection in humans can lead to a wide range of clinical manifestations, from mild fever to potentially fatal dengue shock syndrome. The incidence of dengue fever is on the rise in tropical countries. Due to the increasing incidence of dengue fever worldwide, atypical manifestations of the disease are increasingly reported. In this article we report a patient with dengue haemorrhagic fever who presented with reversible splenial lesion syndrome.

CASE PRESENTATION: A 24-year-old Sri Lankan man who presented with fever and confusion was eventually diagnosed to have reversible splenial lesion syndrome based on brain imaging. Clinical, serological and haematological parameters confirmed a diagnosis of dengue haemorrhagic fever. His presentation, assessment, and management are described in this case report.

CONCLUSION: Reversible splenial lesion syndrome is a condition which is radiologically characterized by reversible lesion in the splenium of the corpus callosum. It is associated with infectious and non-infectious aetiologies. This case report highlights the occurrence of reversible splenial lesion syndrome as a presenting feature of the expanding list of unusual neurological manifestations of dengue infection.}, } @article {pmid29945668, year = {2018}, author = {Onyango, CG and Ogonda, L and Guyah, B and Okoth, P and Shiluli, C and Humwa, F and Opollo, V}, title = {Correction to: Seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors in Homabay, Kisumu and Siaya counties in western Kenya.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {410}, pmid = {29945668}, issn = {1756-0500}, abstract = {Following publication of the original article [1], the authors reported that for two of the authors, Felix Humwa and Vallarie Opollo, an incorrect affiliation has been given. In this Correction the incorrect and correct affiliations are listed.}, } @article {pmid29945666, year = {2018}, author = {Kobaek-Larsen, M and Nielsen, DS and Kot, W and Krych, Ł and Christensen, LP and Baatrup, G}, title = {Effect of the dietary polyacetylenes falcarinol and falcarindiol on the gut microbiota composition in a rat model of colorectal cancer.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {411}, pmid = {29945666}, issn = {1756-0500}, mesh = {Animals ; Colorectal Neoplasms/drug therapy/*microbiology ; Denmark ; Diet ; Diynes/*pharmacology ; Fatty Alcohols/*pharmacology ; Gastrointestinal Microbiome/*drug effects ; Male ; Polyynes ; RNA, Ribosomal, 16S ; Rats ; Rats, Inbred F344 ; }, abstract = {OBJECTIVES: (3R)-Falcarinol (FaOH) and (3R,8S)-falcarindiol (FaDOH) have previously been shown to reduce the number of neoplastic lesions and the growth rate of polyps in the colon of azoxymethane (AOM) treated rats. Based on previous investigations, it appears that different mechanisms of actions are involved in the antineoplastic effect of FaOH and FaDOH. One mechanism of action may be related to the antibacterial effect of FaOH and FaDOH and thus their effect on the gut microbiota. This study aimed to determine the effect of FaOH and FaDOH on gut microbiota composition of AOM treated rats.

RESULTS: Azoxymethane treated rats were fed either a standard rat diet or a rat diet supplemented with FaOH and FaDOH. The gut microbiota of AOM-induced rats was determined by 16S rRNA gene-amplicon sequencing. Analysis of fecal cecum samples demonstrated a significant gut microbiota change in rats receiving standard rat diet supplemented with FaOH and FaDOH compared with the control group that only received the rat diet. Comparison of the gut microbiota of rats who developed large neoplasms in the colon with rats without large neoplasms showed that the gut microbiota was significantly different in rats who developed large colon neoplasms compared to rats with no macroscopic colon neoplasms.}, } @article {pmid29945620, year = {2018}, author = {Hannan, AJ}, title = {Synaptopathy, circuitopathy and the computational biology of Huntington's disease.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {71}, pmid = {29945620}, issn = {1741-7007}, mesh = {*Coculture Techniques ; Computational Biology ; Humans ; *Huntington Disease ; Phenotype ; Synapses ; }, abstract = {Huntington's disease (HD) is one of the most common tandem repeat disorders and presents as a unique trilogy of cognitive, psychiatric and motor symptoms. One of the major mysteries of HD is why it selectively affects specific neuronal populations. A new article in BMC Biology provides a piece in the puzzle of pathogenesis. By demonstrating the delicate relationship between cortical and striatal neurons, it provokes broader questions of how we might understand HD as a disorder of synapses, neural circuits and systems biology.}, } @article {pmid29945611, year = {2018}, author = {Schmidt, ME and Buren, C and Mackay, JP and Cheung, D and Dal Cengio, L and Raymond, LA and Hayden, MR}, title = {Altering cortical input unmasks synaptic phenotypes in the YAC128 cortico-striatal co-culture model of Huntington disease.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {58}, pmid = {29945611}, issn = {1741-7007}, support = {FDN-143210//CIHR/Canada ; FDN-154278//CIHR/Canada ; MOP-84438//CIHR/Canada ; }, abstract = {BACKGROUND: Huntington disease (HD) is a fatal neurodegenerative disorder caused by a CAG expansion in the huntingtin (HTT) gene, leading to selective and progressive neuronal death predominantly in the striatum. Mutant HTT expression causes dysfunctional cortico-striatal (CS) transmission, loss of CS synapses, and striatal medium spiny neuron (MSN) dendritic spine instability prior to neuronal death. Co-culturing cortical and striatal neurons in vitro promotes the formation of functional CS synapses and is a widely used approach to elucidate pathogenic mechanisms of HD and to validate potential synapto-protective therapies. A number of relevant in vivo synaptic phenotypes from the YAC128 HD mouse model, which expresses full-length transgenic human mutant HTT, are recapitulated in CS co-culture by 21 days in vitro (DIV). However, striatal spine loss, which occurs in HD patients and in vivo animal models, has been observed in YAC128 CS co-culture in some studies but not in others, leading to difficulties in reproducing and interpreting results. Here, we investigated whether differences in the relative proportion of cortical and striatal neurons alter YAC128 synaptic phenotypes in this model.

RESULTS: YAC128 MSNs in 1:1 CS co-culture exhibited impaired dendritic length and complexity compared to wild-type, whereas reducing cortical input using a 1:3 CS ratio revealed a dramatic loss of YAC128 MSN dendritic spines. Chimeric experiments determined that this spine instability was primarily cell autonomous, depending largely on mutant HTT expression in striatal neurons. Moreover, we found that spontaneous electrophysiological MSN activity correlated closely with overall dendritic length, with no differences observed between genotypes in 1:3 co-cultures despite significant YAC128 spine loss. Finally, limiting cortical input with a 1:3 CS ratio impaired the basal survival of YAC128 neurons at DIV21, and this was partially selective for dopamine- and cAMP-regulated phosphoprotein 32-positive MSNs.

CONCLUSIONS: Our findings reconcile previous discordant reports of spine loss in this model, and improve the utility and reliability of the CS co-culture for the development of novel therapeutic strategies for HD.}, } @article {pmid29945570, year = {2018}, author = {Clarke, TH and Brinkac, LM and Inman, JM and Sutton, G and Fouts, DE}, title = {PanACEA: a bioinformatics tool for the exploration and visualization of bacterial pan-chromosomes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {246}, pmid = {29945570}, issn = {1471-2105}, support = {U19 AI110819/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Bacterial pan-genomes, comprised of conserved and variable genes across multiple sequenced bacterial genomes, allow for identification of genomic regions that are phylogenetically discriminating or functionally important. Pan-genomes consist of large amounts of data, which can restrict researchers ability to locate and analyze these regions. Multiple software packages are available to visualize pan-genomes, but currently their ability to address these concerns are limited by using only pre-computed data sets, prioritizing core over variable gene clusters, or by not accounting for pan-chromosome positioning in the viewer.

RESULTS: We introduce PanACEA (Pan-genome Atlas with Chromosome Explorer and Analyzer), which utilizes locally-computed interactive web-pages to view ordered pan-genome data. It consists of multi-tiered, hierarchical display pages that extend from pan-chromosomes to both core and variable regions to single genes. Regions and genes are functionally annotated to allow for rapid searching and visual identification of regions of interest with the option that user-supplied genomic phylogenies and metadata can be incorporated. PanACEA's memory and time requirements are within the capacities of standard laptops. The capability of PanACEA as a research tool is demonstrated by highlighting a variable region important in differentiating strains of Enterobacter hormaechei.

CONCLUSIONS: PanACEA can rapidly translate the results of pan-chromosome programs into an intuitive and interactive visual representation. It will empower researchers to visually explore and identify regions of the pan-chromosome that are most biologically interesting, and to obtain publication quality images of these regions.}, } @article {pmid29945559, year = {2018}, author = {Stricker, G and Galinier, M and Gagneur, J}, title = {GenoGAM 2.0: scalable and efficient implementation of genome-wide generalized additive models for gigabase-scale genomes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {247}, pmid = {29945559}, issn = {1471-2105}, abstract = {BACKGROUND: GenoGAM (Genome-wide generalized additive models) is a powerful statistical modeling tool for the analysis of ChIP-Seq data with flexible factorial design experiments. However large runtime and memory requirements of its current implementation prohibit its application to gigabase-scale genomes such as mammalian genomes.

RESULTS: Here we present GenoGAM 2.0, a scalable and efficient implementation that is 2 to 3 orders of magnitude faster than the previous version. This is achieved by exploiting the sparsity of the model using the SuperLU direct solver for parameter fitting, and sparse Cholesky factorization together with the sparse inverse subset algorithm for computing standard errors. Furthermore the HDF5 library is employed to store data efficiently on hard drive, reducing memory footprint while keeping I/O low. Whole-genome fits for human ChIP-seq datasets (ca. 300 million parameters) could be obtained in less than 9 hours on a standard 60-core server. GenoGAM 2.0 is implemented as an open source R package and currently available on GitHub. A Bioconductor release of the new version is in preparation.

CONCLUSIONS: We have vastly improved the performance of the GenoGAM framework, opening up its application to all types of organisms. Moreover, our algorithmic improvements for fitting large GAMs could be of interest to the statistical community beyond the genomics field.}, } @article {pmid29945554, year = {2018}, author = {Everson, JL and Fink, DM and Chung, HM and Sun, MR and Lipinski, RJ}, title = {Identification of sonic hedgehog-regulated genes and biological processes in the cranial neural crest mesenchyme by comparative transcriptomics.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {497}, pmid = {29945554}, issn = {1471-2164}, support = {R00DE022010//National Institute of Dental and Craniofacial Research/ ; T32ES007015//National Institute of Environmental Health Sciences/ ; }, mesh = {Cell Cycle/genetics/physiology ; Cell Proliferation/genetics/physiology ; Gene Expression Regulation, Developmental/genetics/physiology ; Hedgehog Proteins/genetics/*metabolism ; Humans ; Neural Crest/*cytology/*metabolism ; Signal Transduction/genetics/physiology ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: The evolutionarily conserved Sonic Hedgehog (Shh) signaling pathway is essential for embryogenesis and orofacial development. SHH ligand secreted from the surface ectoderm activates pathway activity in the underlying cranial neural crest cell (cNCC)-derived mesenchyme of the developing upper lip and palate. Disruption of Shh signaling causes orofacial clefts, but the biological action of Shh signaling and the full set of Shh target genes that mediate normal and abnormal orofacial morphogenesis have not been described.

RESULTS: Using comparative transcriptional profiling, we have defined the Shh-regulated genes of the cNCC-derived mesenchyme. Enrichment analysis demonstrated that in cultured cNCCs, Shh-regulated genes are involved in smooth muscle and chondrocyte differentiation, as well as regulation of the Forkhead family of transcription factors, G1/S cell cycle transition, and angiogenesis. Next, this gene set from Shh-activated cNCCs in vitro was compared to the set of genes dysregulated in the facial primordia in vivo during the initial pathogenesis of Shh pathway inhibitor-induced orofacial clefting. Functional gene annotation enrichment analysis of the 112 Shh-regulated genes with concordant expression changes linked Shh signaling to interdependent and unique biological processes including mesenchyme development, cell adhesion, cell proliferation, cell migration, angiogenesis, perivascular cell markers, and orofacial clefting.

CONCLUSIONS: We defined the Shh-regulated transcriptome of the cNCC-derived mesenchyme by comparing the expression signatures of Shh-activated cNCCs in vitro to primordial midfacial tissues exposed to the Shh pathway inhibitor in vivo. In addition to improving our understanding of cNCC biology by determining the identity and possible roles of cNCC-specific Shh target genes, this study presents novel candidate genes whose examination in the context of human orofacial clefting etiology is warranted.}, } @article {pmid29945553, year = {2018}, author = {Riaz, S and De Lorenzis, G and Velasco, D and Koehmstedt, A and Maghradze, D and Bobokashvili, Z and Musayev, M and Zdunic, G and Laucou, V and Andrew Walker, M and Failla, O and Preece, JE and Aradhya, M and Arroyo-Garcia, R}, title = {Genetic diversity analysis of cultivated and wild grapevine (Vitis vinifera L.) accessions around the Mediterranean basin and Central Asia.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {137}, pmid = {29945553}, issn = {1471-2229}, support = {RTA2014-00016-C03-01//INIA/ ; PRX12/00036//Salvador de Madariaga Program, Ministry of Education, Spain/ ; }, abstract = {BACKGROUND: The mountainous region between the Caucasus and China is considered to be the center of domestication for grapevine. Despite the importance of Central Asia in the history of grape growing, information about the extent and distribution of grape genetic variation in this region is limited in comparison to wild and cultivated grapevines from around the Mediterranean basin. The principal goal of this work was to survey the genetic diversity and relationships among wild and cultivated grape germplasm from the Caucasus, Central Asia, and the Mediterranean basin collectively to understand gene flow, possible domestication events and adaptive introgression.

RESULTS: A total of 1378 wild and cultivated grapevines collected around the Mediterranean basin and from Central Asia were tested with a set of 20 nuclear SSR markers. Genetic data were analyzed (Cluster analysis, Principal Coordinate Analysis and STRUCTURE) to identify groups, and the results were validated by Nei's genetic distance, pairwise FST analysis and assignment tests. All of these analyses identified three genetic groups: G1, wild accessions from Croatia, France, Italy and Spain; G2, wild accessions from Armenia, Azerbaijan and Georgia; and G3, cultivars from Spain, France, Italy, Georgia, Iran, Pakistan and Turkmenistan, which included a small group of wild accessions from Georgia and Croatia. Wild accessions from Georgia clustered with cultivated grape from the same area (proles pontica), but also with Western Europe (proles occidentalis), supporting Georgia as the ancient center of grapevine domestication. In addition, cluster analysis indicated that Western European wild grapes grouped with cultivated grapes from the same area, suggesting that the cultivated proles occidentalis contributed more to the early development of wine grapes than the wild vines from Eastern Europe.

CONCLUSIONS: The analysis of genetic relationships among the tested genotypes provided evidence of genetic relationships between wild and cultivated accessions in the Mediterranean basin and Central Asia. The genetic structure indicated a considerable amount of gene flow, which limited the differentiation between the two subspecies. The results also indicated that grapes with mixed ancestry occur in the regions where wild grapevines were domesticated.}, } @article {pmid29945552, year = {2018}, author = {Wu, S and Liu, Y and Guo, W and Cheng, X and Ren, X and Chen, S and Li, X and Duan, Y and Sun, Q and Yang, X}, title = {Identification and characterization of long noncoding RNAs and mRNAs expression profiles related to postnatal liver maturation of breeder roosters using Ribo-zero RNA sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {498}, pmid = {29945552}, issn = {1471-2164}, support = {2017YFD0502200, 20170500500//the National Key Research and Development Projects/ ; 2017TSCXL-NY-04-04, 2015KTCQ02-19//the program for Shaanxi science & technology/ ; }, mesh = {Animals ; Chickens ; Gene Expression Profiling/methods ; Liver/*metabolism ; Male ; RNA, Long Noncoding/*genetics ; RNA, Messenger/*genetics ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: The liver is mainly hematopoietic in the embryo, and converts into a major metabolic organ in the adult. Therefore, it is intensively remodeled after birth to adapt and perform adult functions. Long non-coding RNAs (lncRNAs) are involved in organ development and cell differentiation, likely they have potential roles in regulating postnatal liver development. Herein, in order to understand the roles of lncRNAs in postnatal liver maturation, we analyzed the lncRNAs and mRNAs expression profiles in immature and mature livers from one-day-old and adult (40 weeks of age) breeder roosters by Ribo-Zero RNA-Sequencing.

RESULTS: Around 21,939 protein-coding genes and 2220 predicted lncRNAs were expressed in livers of breeder roosters. Compared to protein-coding genes, the identified chicken lncRNAs shared fewer exons, shorter transcript length, and significantly lower expression levels. Notably, in comparison between the livers of newborn and adult breeder roosters, a total of 1570 mRNAs and 214 lncRNAs were differentially expressed with the criteria of log2fold change > 1 or < - 1 and P values < 0.05, which were validated by qPCR using randomly selected five mRNAs and five lncRNAs. Further GO and KEGG analyses have revealed that the differentially expressed mRNAs were involved in the hepatic metabolic and immune functional changes, as well as some biological processes and pathways including cell proliferation, apoptotic and cell cycle that are implicated in the development of liver. We also investigated the cis- and trans- regulatory effects of differentially expressed lncRNAs on its target genes. GO and KEGG analyses indicated that these lncRNAs had their neighbor protein coding genes and trans-regulated genes associated with adapting of adult hepatic functions, as well as some pathways involved in liver development, such as cell cycle pathway, Notch signaling pathway, Hedgehog signaling pathway, and Wnt signaling pathway.

CONCLUSIONS: This study provides a catalog of mRNAs and lncRNAs related to postnatal liver maturation of chicken, and will contribute to a fuller understanding of biological processes or signaling pathways involved in significant functional transition during postnatal liver development that differentially expressed genes and lncRNAs could take part in.}, } @article {pmid29945550, year = {2018}, author = {Sun, M and Voorrips, RE and Steenhuis-Broers, G and Van't Westende, W and Vosman, B}, title = {Reduced phloem uptake of Myzus persicae on an aphid resistant pepper accession.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {138}, pmid = {29945550}, issn = {1471-2229}, support = {PPS 1409-029//Ministerie van Economische Zaken/ ; }, abstract = {BACKGROUND: The green peach aphid (GPA), Myzus persicae, is economically one of the most threatening pests in pepper cultivation, which not only causes direct damage but also transmits many viruses. Breeding aphid resistant pepper varieties is a promising and environmentally friendly method to control aphid populations in the field and in the greenhouse. Until now, no strong sources of resistance against the GPA have been identified. Therefore the main aims of this study were to identify pepper materials with a good level of resistance to GPA and to elucidate possible resistance mechanisms.

RESULTS: We screened 74 pepper accessions from different geographical areas for resistance to M. persicae. After four rounds of evaluation we identified one Capsicum baccatum accession (PB2013071) as highly resistant to M. persicae, while the accessions PB2013062 and PB2012022 showed intermediate resistance. The resistance of PB2013071 resulted in a severely reduced uptake of phloem compared to the susceptible accession, as determined by Electrical Penetration Graph (EPG) studies. Feeding of M. persicae induced the expression of callose synthase genes and resulted in callose deposition in the sieve elements in resistant, but not in susceptible plants.

CONCLUSIONS: Three aphid resistant pepper accessions were identified, which will be important for breeding aphid resistant pepper varieties in the future. The most resistant accession PB2013071 showed phloem-based resistance against aphid infestation.}, } @article {pmid29945549, year = {2018}, author = {Wang, X and Yang, S and Chen, Y and Zhang, S and Zhao, Q and Li, M and Gao, Y and Yang, L and Bennetzen, JL}, title = {Comparative genome-wide characterization leading to simple sequence repeat marker development for Nicotiana.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {500}, pmid = {29945549}, issn = {1471-2164}, mesh = {Comparative Genomic Hybridization ; Databases, Genetic ; Genetic Markers/*genetics ; *Genome, Plant ; Genotype ; Internet Access ; Microsatellite Repeats/*genetics ; Polymorphism, Genetic ; Software ; Tobacco/*genetics ; }, abstract = {BACKGROUND: Simple sequence repeats (SSRs) are tandem repeats of DNA that have been used to develop robust genetic markers. These molecular markers are powerful tools for basic and applied studies such as molecular breeding. In the model plants in Nicotiana genus e.g. N. benthamiana, a comprehensive assessment of SSR content has become possible now because several Nicotiana genomes have been sequenced. We conducted a genome-wide SSR characterization and marker development across seven Nicotiana genomes.

RESULTS: Here, we initially characterized 2,483,032 SSRs (repeat units of 1-10 bp) from seven genomic sequences of Nicotiana and developed SSR markers using the GMATA® software package. Of investigated repeat units, mono-, di- and tri-nucleotide SSRs account for 98% of all SSRs in Nicotiana. More complex SSR motifs, although rare, are highly variable between Nicotiana genomes. A total of 1,224,048 non-redundant Nicotiana (NIX) markers were developed, of which 99.98% are novel. An efficient and uniform genotyping protocol for NIX markers was developed and validated. We created a web-based database of NIX marker information including amplicon sizes of alleles in each genome for downloading and online analysis.

CONCLUSIONS: The present work constitutes the first deep characterization of SSRs in seven genomes of Nicotiana, and the development of NIX markers for these SSRs. Our online marker database and an efficient genotyping protocol facilitate the application of these markers. The NIX markers greatly expand Nicotiana marker resources, thus providing a useful tool for future research and breeding. We demonstrate a novel protocol for SSR marker development and utilization at the whole genome scale that can be applied to any lineage of organisms. The Tobacco Markers & Primers Database (TMPD) is available at http://biodb.sdau.edu.cn/tmpd/index.html.}, } @article {pmid29945546, year = {2018}, author = {Cesar, ASM and Regitano, LCA and Reecy, JM and Poleti, MD and Oliveira, PSN and de Oliveira, GB and Moreira, GCM and Mudadu, MA and Tizioto, PC and Koltes, JE and Fritz-Waters, E and Kramer, L and Garrick, D and Beiki, H and Geistlinger, L and Mourão, GB and Zerlotini, A and Coutinho, LL}, title = {Identification of putative regulatory regions and transcription factors associated with intramuscular fat content traits.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {499}, pmid = {29945546}, issn = {1471-2164}, support = {2014/11871-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2014/22884-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2012/23638-8//Fundação de Amparo à Pesquisa do Estado de São Paulo (BR)/ ; }, mesh = {Animals ; Carbohydrate Metabolism/genetics/physiology ; Fatty Acids/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation/genetics/physiology ; Lipid Metabolism/genetics/physiology ; Metabolic Diseases/genetics/metabolism ; Quantitative Trait Loci/*genetics ; Transcription Factors/genetics/*metabolism ; }, abstract = {BACKGROUND: Integration of high throughput DNA genotyping and RNA-sequencing data allows for the identification of genomic regions that control gene expression, known as expression quantitative trait loci (eQTL), on a whole genome scale. Intramuscular fat (IMF) content and carcass composition play important roles in metabolic and physiological processes in mammals because they influence insulin sensitivity and consequently prevalence of metabolic diseases such as obesity and type 2 diabetes. However, limited information is available on the genetic variants and mechanisms associated with IMF deposition in mammals. Thus, our hypothesis was that eQTL analyses could identify putative regulatory regions and transcription factors (TFs) associated with intramuscular fat (IMF) content traits.

RESULTS: We performed an integrative eQTL study in skeletal muscle to identify putative regulatory regions and factors associated with intramuscular fat content traits. Data obtained from skeletal muscle samples of 192 animals was used for association analysis between 461,466 SNPs and the transcription level of 11,808 genes. This yielded 1268 cis- and 10,334 trans-eQTLs, among which we identified nine hotspot regions that each affected the expression of > 119 genes. These putative regulatory regions overlapped with previously identified QTLs for IMF content. Three of the hotspots respectively harbored the transcription factors USF1, EGR4 and RUNX1T1, which are known to play important roles in lipid metabolism. From co-expression network analysis, we further identified modules significantly correlated with IMF content and associated with relevant processes such as fatty acid metabolism, carbohydrate metabolism and lipid metabolism.

CONCLUSION: This study provides novel insights into the link between genotype and IMF content as evident from the expression level. It thereby identifies genomic regions of particular importance and associated regulatory factors. These new findings provide new knowledge about the biological processes associated with genetic variants and mechanisms associated with IMF deposition in mammals.}, } @article {pmid29945545, year = {2018}, author = {Sanguri, S and Gupta, D}, title = {Mannan oligosaccharide requires functional ETC and TLR for biological radiation protection to normal cells.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {9}, pmid = {29945545}, issn = {1471-2121}, support = {09/764(0045)/2012-EMR-1//Council of Scientific and Industrial Research/International ; TC2519/INM-05/2011//Defence Research and Development Organisation (IN)/International ; }, mesh = {Carbocyanines ; Cell Line ; Colony-Forming Units Assay ; Electron Transport/drug effects ; Epithelial Cells/drug effects/*metabolism/radiation effects ; Genes, Reporter ; Humans ; JNK Mitogen-Activated Protein Kinases/metabolism ; Kinetics ; Mannans/*pharmacology ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/drug effects/metabolism ; Mitochondrial Membranes/drug effects/metabolism ; Models, Biological ; NF-kappa B/metabolism ; Oligosaccharides/*pharmacology ; Oxidation-Reduction ; Phospholipids/metabolism ; Phosphorylation/drug effects ; *Radiation Protection ; Radiation, Ionizing ; Reactive Oxygen Species/metabolism ; Superoxide Dismutase/metabolism ; Time Factors ; Toll-Like Receptors/*metabolism ; p38 Mitogen-Activated Protein Kinases/metabolism ; }, abstract = {BACKGROUND: Low LET Ionizing radiation is known to alter intracellular redox balance by inducing free radical generation, which may cause oxidative modification of various cellular biomolecules. The extent of biomolecule-modifications/ damages and changes in vital processes (viz. cellular homeostasis, inter-/intra-cellular signaling, mitochondrial physiology/dynamics antioxidant defence systems) are crucial which in turn determine fate of cells.

RESULTS: In the present study, we expended TLR expressing (normal/ transformed) and TLR null cells; and we have shown that mannan pretreatment in TLR expressing normal cells offers survival advantage against lethal doses of ionizing radiation. On the contrary, mannan pretreatment does not offer any protection against radiation to TLR null cells, NKE ρ° cells and transformed cells. In normal cells, abrupt decrease in mitochondrial membrane potential and endogenous ROS levels occurs following treatment with mannan. We intend to irradiate mannan-pretreated cells at a specific stage of perturbed mitochondrial functioning and ROS levels to comprehend if mannan pretreatment offers any survival advantage against radiation exposure to cells. Interestingly, pre-irradiation treatment of cells with mannan activates NFκB, p38 and JNK, alters mitochondrial physiology, increases expression of Cu/ZnSOD and MnSOD, minimizes oxidation of mitochondrial phospholipids and offers survival advantage in comparison to irradiated group, in TLR expressing normal cells.

CONCLUSION: The study demonstrates that TLR and mitochondrial ETC functions are inevitable in radio-protective efficacy exhibited by mannan.}, } @article {pmid29945543, year = {2018}, author = {Buckley, J and Holub, EB and Koch, MA and Vergeer, P and Mable, BK}, title = {Restriction associated DNA-genotyping at multiple spatial scales in Arabidopsis lyrata reveals signatures of pathogen-mediated selection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {496}, pmid = {29945543}, issn = {1471-2164}, support = {NE/H021183/1//Natural Environment Research Council/ ; NE/H020691/1//Natural Environment Research Council/ ; }, mesh = {Arabidopsis/*genetics ; Gene Frequency/genetics ; Genetic Variation/genetics ; Genotype ; Polymorphism, Single Nucleotide/*genetics ; Selection, Genetic/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Genome scans based on outlier analyses have revolutionized detection of genes involved in adaptive processes, but reports of some forms of selection, such as balancing selection, are still limited. It is unclear whether high throughput genotyping approaches for identification of single nucleotide polymorphisms have sufficient power to detect modes of selection expected to result in reduced genetic differentiation among populations. In this study, we used Arabidopsis lyrata to investigate whether signatures of balancing selection can be detected based on genomic smoothing of Restriction Associated DNA sequencing (RAD-seq) data. We compared how different sampling approaches (both within and between subspecies) and different background levels of polymorphism (inbreeding or outcrossing populations) affected the ability to detect genomic regions showing key signatures of balancing selection, specifically elevated polymorphism, reduced differentiation and shifts towards intermediate allele frequencies. We then tested whether candidate genes associated with disease resistance (R-gene analogs) were detected more frequently in these regions compared to other regions of the genome.

RESULTS: We found that genomic regions showing elevated polymorphism contained a significantly higher density of R-gene analogs predicted to be under pathogen-mediated selection than regions of non-elevated polymorphism, and that many of these also showed evidence for an intermediate site-frequency spectrum based on Tajima's D. However, we found few genomic regions that showed both elevated polymorphism and reduced FST among populations, despite strong background levels of genetic differentiation among populations. This suggests either insufficient power to detect the reduced population structure predicted for genes under balancing selection using sparsely distributed RAD markers, or that other forms of diversifying selection are more common for the R-gene analogs tested.

CONCLUSIONS: Genome scans based on a small number of individuals sampled from a wide range of populations were sufficient to confirm the relative scarcity of signatures of balancing selection across the genome, but also identified new potential disease resistance candidates within genomic regions showing signatures of balancing selection that would be strong candidates for further sequencing efforts.}, } @article {pmid29945240, year = {2018}, author = {Neuman, H and Forsythe, P and Uzan, A and Avni, O and Koren, O}, title = {Antibiotics in early life: dysbiosis and the damage done.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {489-499}, doi = {10.1093/femsre/fuy018}, pmid = {29945240}, issn = {1574-6976}, support = {//CIHR/Canada ; }, mesh = {Anti-Bacterial Agents/*adverse effects/therapeutic use ; Dysbiosis/*chemically induced ; Gastrointestinal Microbiome/*drug effects ; Humans ; }, abstract = {Antibiotics are the most common type of medication prescribed to children, including infants, in the Western world. While use of antibiotics has transformed previously lethal infections into relatively minor diseases, antibiotic treatments can have adverse effects as well. It has been shown in children, adults and animal models that antibiotics dramatically alter the gut microbial composition. Since the gut microbiota plays crucial roles in immunity, metabolism and endocrinology, the effects of antibiotics on the microbiota may lead to further health complications. In this review, we present an overview of the effects of antibiotics on the microbiome in children, and correlate them to long-lasting complications of obesity, behavior, allergies, autoimmunity and other diseases.}, } @article {pmid29945195, year = {2018}, author = {Liu, X and Wu, Y and Wilson, FP and Yu, K and Lintner, C and Cupples, AM and Mattes, TE}, title = {Integrated methodological approach reveals microbial diversity and functions in aerobic groundwater microcosms adapted to vinyl chloride.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy124}, pmid = {29945195}, issn = {1574-6941}, abstract = {Vinyl chloride (VC), a known human carcinogen, is often formed in groundwater (GW) by incomplete reductive dechlorination of chlorinated ethenes. An integrated microbial ecology approach involving bacterial enrichments and isolations, carbon stable-isotope probing (SIP) and metagenome and genome sequencing was applied to ethene-fed GW microcosms that rapidly transitioned to aerobic growth on VC. Actinobacteria, Proteobacteria and Bacteroidetes dominated the microbial communities in ethene- and VC-grown cultures. SIP with 13C2-VC demonstrated that Nocardioides spp. significantly participated in carbon uptake from VC (52.1%-75.7% enriched in heavy fractions). Sediminibacterium, Pedobacter and Pseudomonas spp. also incorporated 13C from VC into genomic DNA. Ethene- and VC-assimilating Nocardioides sp. strain XL1 was isolated. Sequencing revealed a large (∼300 kbp) plasmid harboring genes encoding alkene monooxygenase and epoxyalkane: coenzyme M transferase, enzymes known to participate in aerobic VC and ethene biodegradation. The plasmid was 100% identical to pNOCA01 found in VC-assimilating Nocardioides sp. strain JS614. Metagenomic analysis of enrichment cultures indicated other bacteria implicated in carbon uptake from VC possessed the genetic potential to detoxify epoxides via epoxide hydrolase or glutathione S-transferase (Pseudomonas) and/or metabolize VC epoxide breakdown products and downstream VC metabolites. This study provides new functional insights into aerobic VC metabolism within a GW microbial community.}, } @article {pmid29945193, year = {2018}, author = {Maurer-Alcalá, XX and Yan, Y and Pilling, OA and Knight, R and Katz, LA}, title = {Twisted Tales: Insights into Genome Diversity of Ciliates Using Single-Cell 'Omics.}, journal = {Genome biology and evolution}, volume = {10}, number = {8}, pages = {1927-1939}, pmid = {29945193}, issn = {1759-6653}, support = {R15 GM113177/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromosomes/genetics ; Ciliophora/*genetics ; Gene Dosage ; *Genetic Variation ; *Genome ; *Genomics ; Germ Cells/metabolism ; Phylogeny ; *Single-Cell Analysis ; }, abstract = {The emergence of robust single-cell 'omics techniques enables studies of uncultivable species, allowing for the (re)discovery of diverse genomic features. In this study, we combine single-cell genomics and transcriptomics to explore genome evolution in ciliates (a > 1 Gy old clade). Analysis of the data resulting from these single-cell 'omics approaches show: 1) the description of the ciliates in the class Karyorelictea as "primitive" is inaccurate because their somatic macronuclei contain loci of varying copy number (i.e., they have been processed by genome rearrangements from the zygotic nucleus); 2) gene-sized somatic chromosomes exist in the class Litostomatea, consistent with Balbiani's (1890) observation of giant chromosomes in this lineage; and 3) gene scrambling exists in the underexplored Postciliodesmatophora (the classes Heterotrichea and Karyorelictea, abbreviated here as the Po-clade), one of two major clades of ciliates. Together these data highlight the complex evolutionary patterns underlying germline genome architectures in ciliates and provide a basis for further exploration of principles of genome evolution in diverse microbial lineages.}, } @article {pmid29945179, year = {2018}, author = {Straub, CT and Counts, JA and Nguyen, DMN and Wu, CH and Zeldes, BM and Crosby, JR and Conway, JM and Otten, JK and Lipscomb, GL and Schut, GJ and Adams, MWW and Kelly, RM}, title = {Biotechnology of extremely thermophilic archaea.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {543-578}, doi = {10.1093/femsre/fuy012}, pmid = {29945179}, issn = {1574-6976}, support = {T32 GM008776/GM/NIGMS NIH HHS/United States ; }, mesh = {Archaea/genetics/*physiology ; Biotechnology/*trends ; *Hot Temperature ; Industrial Microbiology/trends ; Metabolic Engineering/*trends ; }, abstract = {Although the extremely thermophilic archaea (Topt ≥ 70°C) may be the most primitive extant forms of life, they have been studied to a limited extent relative to mesophilic microorganisms. Many of these organisms have unique biochemical and physiological characteristics with important biotechnological implications. These include methanogens that generate methane, fermentative anaerobes that produce hydrogen gas with high efficiency, and acidophiles that can mobilize base, precious and strategic metals from mineral ores. Extremely thermophilic archaea have also been a valuable source of thermoactive, thermostable biocatalysts, but their use as cellular systems has been limited because of the general lack of facile genetics tools. This situation has changed recently, however, thereby providing an important avenue for understanding their metabolic and physiological details and also opening up opportunities for metabolic engineering efforts. Along these lines, extremely thermophilic archaea have recently been engineered to produce a variety of alcohols and industrial chemicals, in some cases incorporating CO2 into the final product. There are barriers and challenges to these organisms reaching their full potential as industrial microorganisms but, if these can be overcome, a new dimension for biotechnology will be forthcoming that strategically exploits biology at high temperatures.}, } @article {pmid29945173, year = {2018}, author = {Mauriello, EMF and Jones, C and Moine, A and Armitage, JP}, title = {Cellular targeting and segregation of bacterial chemosensory systems.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {462-476}, doi = {10.1093/femsre/fuy015}, pmid = {29945173}, issn = {1574-6976}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacteria/metabolism ; *Bacterial Physiological Phenomena ; Bacterial Proteins/*metabolism ; Chemotaxis/physiology ; Membrane Proteins/physiology ; }, abstract = {The bacterial cytoplasm is not a homogeneous solution of macromolecules, but rather a highly organized and compartmentalized space where the clustering and segregation of macromolecular complexes in certain cell regions confers functional efficiency. Bacterial chemoreceptors represent a versatile model system to study the subcellular localization of macromolecules, as they are present in almost all motile bacterial and archaeal species, where they tend to form highly ordered arrays that occupy distinct positions in cells. The positioning of chemoreceptor clusters, as well as their segregation mechanism on cell division, varies from species to species and probably depends on cells size, environment and speed of movement. In this review, we summarize the current understanding of the architecture and the segregation mechanisms of chemoreceptors in a limited number of bacterial model systems and suggest that the pattern of chemoreceptor distribution is coupled to behavioral life-style of that species.}, } @article {pmid29944871, year = {2018}, author = {Schaeffer, J and Tannahill, D and Cioni, JM and Rowlands, D and Keynes, R}, title = {Identification of the extracellular matrix protein Fibulin-2 as a regulator of spinal nerve organization.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {101-114}, doi = {10.1016/j.ydbio.2018.06.014}, pmid = {29944871}, issn = {1095-564X}, mesh = {Animals ; Astrocytes/metabolism/physiology ; Axons/physiology ; Calcium-Binding Proteins/genetics/metabolism/*physiology ; Cell Differentiation/physiology ; Chick Embryo ; Extracellular Matrix/metabolism ; Extracellular Matrix Proteins/genetics/metabolism/*physiology ; Mice ; Neural Crest/metabolism/physiology ; Semaphorin-3A/metabolism ; Somites/physiology ; Spinal Cord/metabolism/physiology ; Spinal Nerves/*embryology ; }, abstract = {During amniote peripheral nervous system development, segmentation ensures the correct patterning of the spinal nerves relative to the vertebral column. Along the antero-posterior (rostro-caudal) axis, each somite-derived posterior half-sclerotome expresses repellent molecules to restrict axon growth and neural crest migration to the permissive anterior half-segment. To identify novel regulators of spinal nerve patterning, we investigated the differential gene expression of anterior and posterior half-sclerotomes in the chick embryo by RNA-sequencing. Several genes encoding extracellular matrix proteins were found to be enriched in either anterior (e.g. Tenascin-C, Laminin alpha 4) or posterior (e.g. Fibulin-2, Fibromodulin, Collagen VI alpha 2) half-sclerotomes. Among them, the extracellular matrix protein Fibulin-2 was found specifically restricted to the posterior half-sclerotome. By using in ovo ectopic expression in chick somites, we found that Fibulin-2 modulates spinal axon growth trajectories in vivo. While no intrinsic axon repellent activity of Fibulin-2 was found, we showed that it enhances the growth cone repulsive activity of Semaphorin 3A in vitro. Some molecules regulating axon growth during development are found to be upregulated in the adult central nervous system (CNS) following traumatic injury. Here, we found increased Fibulin-2 protein levels in reactive astrocytes at the lesion site of a mouse model of CNS injury. Together, these results suggest that the developing vertebral column and the adult CNS share molecular features that control axon growth and plasticity, which may open up the possibility for the identification of novel therapeutic targets for brain and spinal cord injury.}, } @article {pmid29944770, year = {2018}, author = {Karvonen, A and Wagner, CE and Selz, OM and Seehausen, O}, title = {Divergent parasite infections in sympatric cichlid species in Lake Victoria.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1313-1329}, doi = {10.1111/jeb.13304}, pmid = {29944770}, issn = {1420-9101}, support = {#263864//Academy of Finland/ ; #292736//Academy of Finland/ ; #310632//Academy of Finland/ ; #3757//European Science Foundation/ ; DEB-1556963//NSF/ ; 3100A0-118293/1//SNSF/ ; 31003A_144046//SNSF/ ; }, abstract = {Parasitism has been proposed as a factor in host speciation, as an agent affecting coexistence of host species in species-rich communities and as a driver of post-speciation diversification. Young adaptive radiations of closely related host species of varying ecological and genomic differentiation provide interesting opportunities to explore interactions between patterns of parasitism, divergence and coexistence of sympatric host species. Here, we explored patterns in ectoparasitism in a community of 16 fully sympatric cichlid species at Makobe Island in Lake Victoria, a model system of vertebrate adaptive radiation. We asked whether host niche, host abundance or host genetic differentiation explains variation in infection patterns. We found significant differences in infections, the magnitude of which was weakly correlated with the extent of genomic divergence between the host species, but more strongly with the main ecological gradient, water depth. These effects were most evident with infections of Cichlidogyrus monogeneans, whereas the only host species with a strictly crevice-dwelling niche, Pundamilia pundamilia, deviated from the general negative relationship between depth and parasitism. In accordance with the Janzen-Connell hypothesis, we also found that host abundance tended to be positively associated with infections in some parasite taxa. Data on the Pundamilia sister species pairs from three other islands with variable degrees of habitat (crevice) specialization suggested that the lower parasite abundance of P. pundamilia at Makobe could result from both habitat specialization and the evolution of specific resistance. Our results support influences of host genetic differentiation and host ecology in determining infections in this diverse community of sympatric cichlid species.}, } @article {pmid29944112, year = {2018}, author = {Wang, Z and Jiang, B and Li, X and Gan, L and Long, X and Zhang, Y and Tian, Y}, title = {Streptomyces populi sp. nov., a novel endophytic actinobacterium isolated from stem of Populus adenopoda Maxim.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2568-2573}, doi = {10.1099/ijsem.0.002877}, pmid = {29944112}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Stems/*microbiology ; Populus/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptomyces/*classification/growth & development/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel endophytic actinobacterium strain, designated A249T, was isolated from the stem of Populus adenopoda collected at Mount Qingcheng in south-west China. Its taxonomic position was determined by using a polyphasic approach. The cultural and morphological characteristics of isolate A249T were consistent with members of the genus Streptomyces. Growth occurred at 10-37 °C, pH 6.0-12.0 and in the presence of 0-4 % (w/v) NaCl. Analysis of the 16S rRNA gene sequence and phylogenetic trees showed the closest phylogenetic relatives to strain A249T were Streptomyces shaanxiensis JCM 16925T (98.0 % 16S rRNA gene sequence similarity) and Streptomyces lanatus JCM 4332T (97.9 %). The DNA-DNA hybridization values between the strain A249T and the two reference strains ranged from 41.4 to 49.4 %. The DNA G+C content was 71.7 mol%. The range of average nucleotide identity values was 81.5-86.7 %. Chemical analysis of cellular components indicated that strain A249T contained ll-diaminopimelic acid, xylose and galactose. The predominant menaquinones were MK-9(H6) and MK-9(H8). The polar lipids were diphosphatidylglycerol, phosphatidylinositol mannosides, phosphatidylethanolamine, two unidentified lipids, one unidentified phospholipid, one unidentified aminolipid and one unidentified aminophospholipid. The major fatty acids comprised C16 : 0, iso-C14 : 0, iso-C15 : 0, iso-C16 : 0, anteiso-C15 : 0 and C16 : 1ω7c. On the basis of the phenotypic and genotypic differentiation of the three tested strains, isolate A249T is proposed to represent a novel species of the genus Streptomyces, named Streptomyces populi sp. nov. The type strain is A249T (=CGMCC 4.7417T=JCM 32175T).}, } @article {pmid29944111, year = {2018}, author = {Khalifa, A and Nakasuji, Y and Saka, N and Honjo, H and Asakawa, S and Watanabe, T}, title = {Ferrigenium kumadai gen. nov., sp. nov., a microaerophilic iron-oxidizing bacterium isolated from a paddy field soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2587-2592}, doi = {10.1099/ijsem.0.002882}, pmid = {29944111}, issn = {1466-5034}, mesh = {Autotrophic Processes ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gallionellaceae/*classification/genetics/isolation & purification ; Iron/metabolism ; Japan ; *Oryza ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {An iron-oxidizing bacterium, designated strain An22T, which was isolated from a paddy field soil in Anjo, Japan, was described taxonomically. Strain An22T was motile by a single polar flagellum, curved-rod, Gram-negative bacterium that was able to grow at 12-37 °C (optimally at 25-30 °C) and at pH 5.2-6.8 (pH 5.9-6.1). The strain grew microaerobically and autotrophically by oxidizing ferrous iron, but did not form stalks, a unique structure of iron oxides. The major cellular fatty acids were C16 : 0 and C16 : 1ω7c/C16 : 1ω6c. The major respiratory quinones were UQ-10 and UQ-8. The strain possessed ribulose-1,5-bisphosphate carboxylase/oxygenase indicating an autotrophic nature via the Calvin-Benson-Bassham cycle. The total DNA G+C content was 61.4 mol%. 16S rRNA gene sequence analysis revealed that strain An22T was affiliated with the class Betaproteobacteria and clustered with iron-oxidizing bacteria, Gallionella ferrugineaJohan (94.8 % similarity) and Ferriphaselus amnicola OYT1T (94.4 %) in the family Gallionellaceae. Based on the low 16S rRNA gene sequence similarity to the phylogenetically closest genera and the combination of unique morphological, physiological and biochemical characteristics, strain An22T represents a novel genus and species within the family Gallionellaceae, for which the name Ferrigenium kumadai gen. nov., sp. nov. is proposed. The type strain is An22T (=JCM 30584T=NBRC 112974T=ATCC TSD-51T).}, } @article {pmid29944109, year = {2018}, author = {Siddiqi, MZ and Liu, Q and Lee, SY and Choi, KD and Im, WT}, title = {Olivibacter ginsenosidimutans sp nov., with ginsenoside converting activity isolated from compost, and reclassification of Pseudosphingobacterium domesticum as Olivibacter domesticus comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2509-2514}, doi = {10.1099/ijsem.0.002819}, pmid = {29944109}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; Composting ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Ginsenosides/metabolism ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic and rod-shaped, bacterium designated as strain BS18T, was isolated from compost and subjected to a polyphasic taxonomic analysis. On the basis of the results of 16S rRNA gene sequence analysis, BS18T represents a member of the genus Olivibacter of the family Sphingobacteriaceaeand is most closely related to Olivibacter oleidegradansTBF2/20.2T (93.7 %), Olivibacter jilunii 14-2AT (93.6 %), Olivibacter ginsengisoli Gsoil 060T (93.6 %), Pseudosphingobacterium domesticumDC186T (93.0 %) and shared ≤93.1 % sequence similarity with the other members of the genus Olivibacter. BS18T contained MK-7 as the predominant quinone, iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 4 (iso-C15 : 0 2-OH and/or C16 : 1ω7c), as the major fatty acids and phosphatidylethanolamine (PE) as main polar lipid. BS18T could be distinguished from the other members of the genus Olivibacter by a number of chemotaxonomic and phenotypic characteristics. On the basis of the results of polyphasic taxonomic analysis, BS18T represents a novel species within the genus, for which the name Olivibacter ginsenosidimutans sp. nov. is proposed. The type strain of Olivibacter ginsenosidimutans is BS18T (=KACC 16612T=JCM 18200T). It is also proposed to transfer Pseudosphingobacterium domesticumto the genus Olivibacter, as Olivibacter domesticus comb. nov. (type strain DC186T=CCUG 54353T=LMG 23837T).}, } @article {pmid29944094, year = {2018}, author = {Li, X and Lai, X and Gan, L and Long, X and Hou, Y and Zhang, Y and Tian, Y}, title = {Streptomyces geranii sp. nov., a novel endophytic actinobacterium isolated from root of Geranium carolinianum L.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2562-2567}, doi = {10.1099/ijsem.0.002876}, pmid = {29944094}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geranium/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptomyces/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel endophytic actinomycete, designated A301T, was isolated from the root of Geranium carolinianum Linn collected from Mount Emei in China and characterized using a polyphasic approach. Growth occurred at 10-37 °C, pH 6-11 and in the presence of 0-5 % NaCl (w/v). Strain A301T contained ll-diaminopimelic acid as the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell hydrolysates included galactose and ribose. The predominant menaquinones were MK-9(H6) and MK-9(H8). The major cellular fatty acids were C15 : 0, C16 : 0, anteiso-C15 : 0 and iso-C16 : 0. The polar lipid profile consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, two unidentified phospholipids, three unidentified lipids and two unidentified aminophospholipids. Strain A301T shared the highest 16S rRNA gene sequence similarity to Streptomyces cinereorubersubsp. fructofermentans NBRC 15396T (98.1 %) and Streptomyces turgidiscabies ATCC 700248T (98.1 %). The DNA-DNA relatedness values between strain A301T and the two above-mentioned members of the genus Streptomyces were 42.6 % and 47.2 %, respectively. The G+C content of the DNA was 70.5 mol%. On the basis of the polyphasic approach and DNA-DNA hybridization data, strain A301T represents a novel species within the genus Streptomyces, for which the name Streptomyces geranii sp. nov. is proposed. The type strain is A301T (=CGMCC 4.7422T=JCM 32177T).}, } @article {pmid29944093, year = {2018}, author = {Zhou, XK and Mi, QL and Yao, JH and Wu, H and Liu, XM and Li, YD and Duan, YQ and Chen, JH and Dang, LZ and Mo, MH and Li, XM and Li, WJ}, title = {Sphingomonas tabacisoli sp. nov., a member of the genus Sphingomonas, isolated from rhizosphere soil of Nicotiana tabacum L.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2574-2579}, doi = {10.1099/ijsem.0.002879}, pmid = {29944093}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Spermidine/analogs & derivatives/chemistry ; Sphingomonas/*classification/genetics/isolation & purification ; Tobacco/*microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-staining-negative, aerobic, motile and rod-shaped bacterium, designated strain X1-8T, was isolated from rhizosphere soil of Nicotiana tabacum L. collected from the tobacco produce base located in Kunming, south-west PR China. Cells showed oxidase-negative and catalase-positive reactions and were motile by means of peritrichous flagella. Growth occurred at 25-40 °C and pH 6.0-8.0 with optimal growth at 30-35 °C, pH 7.0. The major respiratory lipoquinone was Q-10. C16 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) were identified as major cellular fatty acids. The profile of polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, sphingoglycolipid, phosphatidylcholine and one unidentified glycolipid. The major polyamine was sym-homospermidine. The genomic DNA G+C content was 66.5 mol%. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that X1-8T should be affiliated to the genus Sphingomonasand formed a clade with most closely related species Sphingomonas changbaiensisNBRC 104936T. The results of 16S rRNA gene sequences similarity analysis indicated that X1-8T had the highest similarity with S. changbaiensisNBRC 104936T (98.4 %) and lower than 96.0 % with other species of the genus Sphingomonas. DNA-DNA hybridization data indicated that X1-8T represented a novel genomic species of the genus Sphingomonas. The characteristics determined in the polyphasic taxonomic study indicated that X1-8T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas tabacisoli sp. nov. (type strain X1-8T=KCTC 62032T=CGMCC 1.16275T) is proposed.}, } @article {pmid29944092, year = {2018}, author = {Arahal, DR and Lucena, T and Rodrigo-Torres, L and Pujalte, MJ}, title = {Ruegeria denitrificans sp. nov., a marine bacterium in the family Rhodobacteraceae with the potential ability for cyanophycin synthesis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2515-2522}, doi = {10.1099/ijsem.0.002867}, pmid = {29944092}, issn = {1466-5034}, mesh = {Animals ; Bacterial Proteins/biosynthesis ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Mediterranean Sea ; Nucleic Acid Hybridization ; Ostreidae/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Spain ; }, abstract = {Strain CECT 5091T, an aerobic, marine, Gram-reaction- and Gram-stain-negative, chemoheterotrophic bacterium was isolated from oysters harvested off the Spanish Mediterranean coast. Analysis of the 16S rRNA gene sequence placed the strain within the genus Ruegeria, in the family Rhodobacteraceae, with 16S rRNA gene similarities of 98.7, 98.7 and 98.4 % to Ruegeria conchae, Ruegeria atlanticaand Ruegeria arenilitoris, respectively. Average nucleotide identities (ANI) and in silico DNA-DNA hybridization (DDH) were determined, comparing the genome sequence of CECT 5091T with those of the type strains of 12 species of the genus Ruegeria: the values obtained were always below the thresholds (95-96 % ANI, 70 % in silico DDH) used to define genomic species, proving that CECT 5091T represents a novel species of the genus Ruegeria. The strain was slightly halophilic and mesophilic, with optimum growth at 26 °C, pH 7.0 and 3 % salinity, it required sodium and magnesium ions for growth and was able to reduce nitrate to dinitrogen. Carbon sources for growth include some carbohydrates (d-ribose, d-glucose, l-rhamnose, N-acetyl-d-glucosamine) and multiple organic acids and amino acids. The major cellular fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), representing 70 % of the total fatty acids. Carbon monoxide oxidation, cyanophycin synthetic ability and phosphatidylglycerol, diphosphatidylglycerol and phosphatidylcholine production are predicted from genome annotation, while bacteriochlorophyll a production was absent. The DNA G+C content of the genome was 56.7 mol%. We propose the name Ruegeriadenitrificans sp. nov. and strain CECT 5091T (=5OM10T=LMG 29896T) as the type strain for the novel species.}, } @article {pmid29943457, year = {2018}, author = {Molina-Santiago, C}, title = {Insights in a novel gram-positive type IV secretion system.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2334-2336}, doi = {10.1111/1462-2920.14296}, pmid = {29943457}, issn = {1462-2920}, } @article {pmid29943391, year = {2018}, author = {Reales, G and Paixão-Côrtes, VR and Cybis, GB and Gonçalves, GL and Pissinatti, A and Salzano, FM and Bortolini, MC}, title = {Serotonin, behavior, and natural selection in New World monkeys.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1180-1192}, doi = {10.1111/jeb.13295}, pmid = {29943391}, issn = {1420-9101}, abstract = {Traits that undergo massive natural selection pressure, with multiple events of positive selection, are hard to find. Social behaviour, in social animals, is crucial for survival, and genetic networks involved in behaviour, such as those of serotonin (5-HT) and other neurotransmitters, must be the target of natural selection. Here, we used molecular analyses to search for signals of positive selection in the 5-HT system and found such signals in the M3-M4 intracellular domain of the 5-HT3A serotonin receptor subunit (HTR3A) in primates. We detected four amino acid sites with signs of putatively positive selection (398, 403, 432 and 416); the first three showed indications of being selected in New World monkeys (NWM, Platyrrhini), specifically in the Callitrichinae branch. Additionally, we searched for associations of these amino acid variants with social behavioural traits (i.e. sex-biased dispersal, dominance and social monogamy) using classical and Bayesian methods, and found statistically significant associations for unbiased sex dispersal (398L and 416S), unbiased sex dominance (416S) and social monogamy (416S), as well as significant positive correlation between female dispersal and 403G. Furthermore, we found putatively functional protein motifs determined by three selected sites, of which we highlight a ligand motif to GSK3 in the 416S variant, appearing only in Platyrrhini. 5-HT, 5-HT3A receptor and GSK3 are part of a network that participates in neurodevelopment and regulates behaviour, among other functions. We suggest that these genetic variations, together with those found in other neurotransmitter systems, must contribute to adaptive behaviours and consequently to fitness in NWMs.}, } @article {pmid29943091, year = {2018}, author = {Ricci, M and Peona, V and Guichard, E and Taccioli, C and Boattini, A}, title = {Correction to: Transposable Elements Activity is Positively Related to Rate of Speciation in Mammals.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {311}, doi = {10.1007/s00239-018-9850-z}, pmid = {29943091}, issn = {1432-1432}, abstract = {The original version of the article unfortunately contained tagging error in Given and Surname of all the authors.}, } @article {pmid29942512, year = {2018}, author = {Staub, K and Henneberg, M and Galassi, FM and Eppenberger, P and Haeusler, M and Morozova, I and Rühli, FJ and Bender, N}, title = {Increasing variability of body mass and health correlates in Swiss conscripts, a possible role of relaxed natural selection?.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {116-126}, pmid = {29942512}, issn = {2050-6201}, abstract = {Background and objectives: The body mass index (BMI) is an established anthropometric index for the development of obesity-related conditions. However, little is known about the distribution of BMI within a population, especially about this distribution's temporal change. Here, we analysed changes in the distribution of height, weight and BMI over the past 140 years based on data of Swiss conscripts and tested for correlations between anthropometric data and standard blood parameters.

Methods: Height and weight were measured in 59 504 young Swiss males aged 18-19 years during conscription in 1875-79, 1932-36, 1994 and 2010-12. For 65% of conscripts in 2010-12, results of standard blood analysis were available. We calculated descriptive statistics of the distribution of height, weight and BMI over the four time periods and tested for associations between BMI and metabolic parameters.

Results: Average and median body height, body weight and BMI increased over time. Height did no longer increase between 1994 and 2010-12, while weight and BMI still increased over these two decades. Variability ranges of weight and BMI increased over time, while variation of body height remained constant. Elevated levels of metabolic and inflammatory blood parameters were found at both ends of BMI distribution.

Conclusions and implications: Both overweight and underweight subgroups showed similar changes in inflammation parameters, pointing toward related metabolic deficiencies in both conditions. In addition to environmental influences, our results indicate a potential role of relaxed natural selection on genes affecting metabolism and body composition.}, } @article {pmid29942086, year = {2018}, author = {Savage, JE and Jansen, PR and Stringer, S and Watanabe, K and Bryois, J and de Leeuw, CA and Nagel, M and Awasthi, S and Barr, PB and Coleman, JRI and Grasby, KL and Hammerschlag, AR and Kaminski, JA and Karlsson, R and Krapohl, E and Lam, M and Nygaard, M and Reynolds, CA and Trampush, JW and Young, H and Zabaneh, D and Hägg, S and Hansell, NK and Karlsson, IK and Linnarsson, S and Montgomery, GW and Muñoz-Manchado, AB and Quinlan, EB and Schumann, G and Skene, NG and Webb, BT and White, T and Arking, DE and Avramopoulos, D and Bilder, RM and Bitsios, P and Burdick, KE and Cannon, TD and Chiba-Falek, O and Christoforou, A and Cirulli, ET and Congdon, E and Corvin, A and Davies, G and Deary, IJ and DeRosse, P and Dickinson, D and Djurovic, S and Donohoe, G and Conley, ED and Eriksson, JG and Espeseth, T and Freimer, NA and Giakoumaki, S and Giegling, I and Gill, M and Glahn, DC and Hariri, AR and Hatzimanolis, A and Keller, MC and Knowles, E and Koltai, D and Konte, B and Lahti, J and Le Hellard, S and Lencz, T and Liewald, DC and London, E and Lundervold, AJ and Malhotra, AK and Melle, I and Morris, D and Need, AC and Ollier, W and Palotie, A and Payton, A and Pendleton, N and Poldrack, RA and Räikkönen, K and Reinvang, I and Roussos, P and Rujescu, D and Sabb, FW and Scult, MA and Smeland, OB and Smyrnis, N and Starr, JM and Steen, VM and Stefanis, NC and Straub, RE and Sundet, K and Tiemeier, H and Voineskos, AN and Weinberger, DR and Widen, E and Yu, J and Abecasis, G and Andreassen, OA and Breen, G and Christiansen, L and Debrabant, B and Dick, DM and Heinz, A and Hjerling-Leffler, J and Ikram, MA and Kendler, KS and Martin, NG and Medland, SE and Pedersen, NL and Plomin, R and Polderman, TJC and Ripke, S and van der Sluis, S and Sullivan, PF and Vrieze, SI and Wright, MJ and Posthuma, D}, title = {Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {912-919}, doi = {10.1038/s41588-018-0152-6}, pmid = {29942086}, issn = {1546-1718}, support = {R01 AG049789/AG/NIA NIH HHS/United States ; R01 MH079800/MH/NIMH NIH HHS/United States ; P20 AA017828/AA/NIAAA NIH HHS/United States ; K01 MH098126/MH/NIMH NIH HHS/United States ; R01 DA033369/DA/NIDA NIH HHS/United States ; K01 MH085812/MH/NIMH NIH HHS/United States ; PL1 MH083271/MH/NIMH NIH HHS/United States ; R01 MH085018/MH/NIMH NIH HHS/United States ; RL1 MH083269/MH/NIMH NIH HHS/United States ; UL1 DE019580/DE/NIDCR NIH HHS/United States ; R01 MH085772/MH/NIMH NIH HHS/United States ; R01 AG037985/AG/NIA NIH HHS/United States ; R01 AG028555/AG/NIA NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; U54 EB020403/EB/NIBIB NIH HHS/United States ; PL1 NS062410/NS/NINDS NIH HHS/United States ; R03 AG045633/AG/NIA NIH HHS/United States ; P50 AA022537/AA/NIAAA NIH HHS/United States ; K02 AA018755/AA/NIAAA NIH HHS/United States ; P50 MH080173/MH/NIMH NIH HHS/United States ; P01 AG008761/AG/NIA NIH HHS/United States ; R37 AA011408/AA/NIAAA NIH HHS/United States ; R01 DA037904/DA/NIDA NIH HHS/United States ; R01 AA023974/AA/NIAAA NIH HHS/United States ; K23 MH077807/MH/NIMH NIH HHS/United States ; S10 OD018164/OD/NIH HHS/United States ; R01 MH092515/MH/NIMH NIH HHS/United States ; R01 AG010175/AG/NIA NIH HHS/United States ; RL1 DA024853/DA/NIDA NIH HHS/United States ; R01 MH080912/MH/NIMH NIH HHS/United States ; }, abstract = {Intelligence is highly heritable1 and a major determinant of human health and well-being2. Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.}, } @article {pmid29942085, year = {2018}, author = {Nagel, M and Jansen, PR and Stringer, S and Watanabe, K and de Leeuw, CA and Bryois, J and Savage, JE and Hammerschlag, AR and Skene, NG and Muñoz-Manchado, AB and , and White, T and Tiemeier, H and Linnarsson, S and Hjerling-Leffler, J and Polderman, TJC and Sullivan, PF and van der Sluis, S and Posthuma, D}, title = {Meta-analysis of genome-wide association studies for neuroticism in 449,484 individuals identifies novel genetic loci and pathways.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {920-927}, doi = {10.1038/s41588-018-0151-7}, pmid = {29942085}, issn = {1546-1718}, abstract = {Neuroticism is an important risk factor for psychiatric traits, including depression1, anxiety2,3, and schizophrenia4-6. At the time of analysis, previous genome-wide association studies7-12 (GWAS) reported 16 genomic loci associated to neuroticism10-12. Here we conducted a large GWAS meta-analysis (n = 449,484) of neuroticism and identified 136 independent genome-wide significant loci (124 new at the time of analysis), which implicate 599 genes. Functional follow-up analyses showed enrichment in several brain regions and involvement of specific cell types, including dopaminergic neuroblasts (P = 3.49 × 10-8), medium spiny neurons (P = 4.23 × 10-8), and serotonergic neurons (P = 1.37 × 10-7). Gene set analyses implicated three specific pathways: neurogenesis (P = 4.43 × 10-9), behavioral response to cocaine processes (P = 1.84 × 10-7), and axon part (P = 5.26 × 10-8). We show that neuroticism's genetic signal partly originates in two genetically distinguishable subclusters13 ('depressed affect' and 'worry'), suggesting distinct causal mechanisms for subtypes of individuals. Mendelian randomization analysis showed unidirectional and bidirectional effects between neuroticism and multiple psychiatric traits. These results enhance neurobiological understanding of neuroticism and provide specific leads for functional follow-up experiments.}, } @article {pmid29942084, year = {2018}, author = {Domman, D and Chowdhury, F and Khan, AI and Dorman, MJ and Mutreja, A and Uddin, MI and Paul, A and Begum, YA and Charles, RC and Calderwood, SB and Bhuiyan, TR and Harris, JB and LaRocque, RC and Ryan, ET and Qadri, F and Thomson, NR}, title = {Defining endemic cholera at three levels of spatiotemporal resolution within Bangladesh.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {951-955}, pmid = {29942084}, issn = {1546-1718}, support = {U01 AI077883/AI/NIAID NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 AI106878/AI/NIAID NIH HHS/United States ; U01 AI058935/AI/NIAID NIH HHS/United States ; D43 TW005572/TW/FIC NIH HHS/United States ; R01 AI103055/AI/NIAID NIH HHS/United States ; R56 AI106878/AI/NIAID NIH HHS/United States ; K43 TW010362/TW/FIC NIH HHS/United States ; }, abstract = {Although much focus is placed on cholera epidemics, the greatest burden occurs in settings in which cholera is endemic, including areas of South Asia, Africa and now Haiti1,2. Dhaka, Bangladesh is a megacity that is hyper-endemic for cholera, and experiences two regular seasonal outbreaks of cholera each year3. Despite this, a detailed understanding of the diversity of Vibrio cholerae strains circulating in this setting, and their relationships to annual outbreaks, has not yet been obtained. Here we performed whole-genome sequencing of V. cholerae across several levels of focus and scale, at the maximum possible resolution. We analyzed bacterial isolates to define cholera dynamics at multiple levels, ranging from infection within individuals, to disease dynamics at the household level, to regional and intercontinental cholera transmission. Our analyses provide a genomic framework for understanding cholera diversity and transmission in an endemic setting.}, } @article {pmid29942083, year = {2018}, author = {Hormozdiari, F and Gazal, S and van de Geijn, B and Finucane, HK and Ju, CJ and Loh, PR and Schoech, A and Reshef, Y and Liu, X and O'Connor, L and Gusev, A and Eskin, E and Price, AL}, title = {Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {1041-1047}, pmid = {29942083}, issn = {1546-1718}, support = {R01 MH101782/MH/NIMH NIH HHS/United States ; T32 DK110919/DK/NIDDK NIH HHS/United States ; U01 HG009379/HG/NHGRI NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; R01 MH101244/MH/NIMH NIH HHS/United States ; R01 MH109978/MH/NIMH NIH HHS/United States ; }, abstract = {There is increasing evidence that many risk loci found using genome-wide association studies are molecular quantitative trait loci (QTLs). Here we introduce a new set of functional annotations based on causal posterior probabilities of fine-mapped molecular cis-QTLs, using data from the Genotype-Tissue Expression (GTEx) and BLUEPRINT consortia. We show that these annotations are more strongly enriched for heritability (5.84× for eQTLs; P = 1.19 × 10-31) across 41 diseases and complex traits than annotations containing all significant molecular QTLs (1.80× for expression (e)QTLs). eQTL annotations obtained by meta-analyzing all GTEx tissues generally performed best, whereas tissue-specific eQTL annotations produced stronger enrichments for blood- and brain-related diseases and traits. eQTL annotations restricted to loss-of-function intolerant genes were even more enriched for heritability (17.06×; P = 1.20 × 10-35). All molecular QTLs except splicing QTLs remained significantly enriched in joint analysis, indicating that each of these annotations is uniquely informative for disease and complex trait architectures.}, } @article {pmid29942082, year = {2018}, author = {Heyne, HO and Singh, T and Stamberger, H and Abou Jamra, R and Caglayan, H and Craiu, D and De Jonghe, P and Guerrini, R and Helbig, KL and Koeleman, BPC and Kosmicki, JA and Linnankivi, T and May, P and Muhle, H and Møller, RS and Neubauer, BA and Palotie, A and Pendziwiat, M and Striano, P and Tang, S and Wu, S and , and Poduri, A and Weber, YG and Weckhuysen, S and Sisodiya, SM and Daly, MJ and Helbig, I and Lal, D and Lemke, JR}, title = {De novo variants in neurodevelopmental disorders with epilepsy.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {1048-1053}, doi = {10.1038/s41588-018-0143-7}, pmid = {29942082}, issn = {1546-1718}, abstract = {Epilepsy is a frequent feature of neurodevelopmental disorders (NDDs), but little is known about genetic differences between NDDs with and without epilepsy. We analyzed de novo variants (DNVs) in 6,753 parent-offspring trios ascertained to have different NDDs. In the subset of 1,942 individuals with NDDs with epilepsy, we identified 33 genes with a significant excess of DNVs, of which SNAP25 and GABRB2 had previously only limited evidence of disease association. Joint analysis of all individuals with NDDs also implicated CACNA1E as a novel disease-associated gene. Comparing NDDs with and without epilepsy, we found missense DNVs, DNVs in specific genes, age of recruitment, and severity of intellectual disability to be associated with epilepsy. We further demonstrate the extent to which our results affect current genetic testing as well as treatment, emphasizing the benefit of accurate genetic diagnosis in NDDs with epilepsy.}, } @article {pmid29942075, year = {2018}, author = {Wang, W and Timonen, JVI and Carlson, A and Drotlef, DM and Zhang, CT and Kolle, S and Grinthal, A and Wong, TS and Hatton, B and Kang, SH and Kennedy, S and Chi, J and Blough, RT and Sitti, M and Mahadevan, L and Aizenberg, J}, title = {Multifunctional ferrofluid-infused surfaces with reconfigurable multiscale topography.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {77-82}, doi = {10.1038/s41586-018-0250-8}, pmid = {29942075}, issn = {1476-4687}, abstract = {Developing adaptive materials with geometries that change in response to external stimuli provides fundamental insights into the links between the physical forces involved and the resultant morphologies and creates a foundation for technologically relevant dynamic systems1,2. In particular, reconfigurable surface topography as a means to control interfacial properties3 has recently been explored using responsive gels4, shape-memory polymers5, liquid crystals6-8 and hybrid composites9-14, including magnetically active slippery surfaces12-14. However, these designs exhibit a limited range of topographical changes and thus a restricted scope of function. Here we introduce a hierarchical magneto-responsive composite surface, made by infiltrating a ferrofluid into a microstructured matrix (termed ferrofluid-containing liquid-infused porous surfaces, or FLIPS). We demonstrate various topographical reconfigurations at multiple length scales and a broad range of associated emergent behaviours. An applied magnetic-field gradient induces the movement of magnetic nanoparticles suspended in the ferrofluid, which leads to microscale flow of the ferrofluid first above and then within the microstructured surface. This redistribution changes the initially smooth surface of the ferrofluid (which is immobilized by the porous matrix through capillary forces) into various multiscale hierarchical topographies shaped by the size, arrangement and orientation of the confining microstructures in the magnetic field. We analyse the spatial and temporal dynamics of these reconfigurations theoretically and experimentally as a function of the balance between capillary and magnetic pressures15-19 and of the geometric anisotropy of the FLIPS system. Several interesting functions at three different length scales are demonstrated: self-assembly of colloidal particles at the micrometre scale; regulated flow of liquid droplets at the millimetre scale; and switchable adhesion and friction, liquid pumping and removal of biofilms at the centimetre scale. We envision that FLIPS could be used as part of integrated control systems for the manipulation and transport of matter, thermal management, microfluidics and fouling-release materials.}, } @article {pmid29942074, year = {2018}, author = {Marques, DA and Jones, FC and Di Palma, F and Kingsley, DM and Reimchen, TE}, title = {Experimental evidence for rapid genomic adaptation to a new niche in an adaptive radiation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1128-1138}, doi = {10.1038/s41559-018-0581-8}, pmid = {29942074}, issn = {2397-334X}, support = {P50 HG002568/HG/NHGRI NIH HHS/United States ; }, abstract = {A substantial part of biodiversity is thought to have arisen from adaptive radiations in which one lineage rapidly diversified into multiple lineages specialized to many different niches. However, selection and drift reduce genetic variation during adaptation to new niches and may thus prevent or slow down further niche shifts. We tested whether rapid adaptation is still possible from a highly derived ecotype in the adaptive radiation of threespine stickleback on the Haida Gwaii archipelago, Western Canada. In a 19-year selection experiment, we let giant sticklebacks from a large blackwater lake evolve in a small clearwater pond without vertebrate predators. A total of 56 whole genomes from the experiment and 26 natural populations revealed that adaptive genomic change was rapid in many small genomic regions and encompassed 75% of the change between 12,000-year-old ecotypes. Genomic change was as fast as phenotypic change in defence and trophic morphology, and both were largely parallel between the short-term selection experiment and long-term natural adaptive radiation. Our results show that functionally relevant standing genetic variation can persist in derived radiation members, allowing adaptive radiations to unfold very rapidly.}, } @article {pmid29942022, year = {2018}, author = {Mitchell, EG and Kenchington, CG}, title = {The utility of height for the Ediacaran organisms of Mistaken Point.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1218-1222}, doi = {10.1038/s41559-018-0591-6}, pmid = {29942022}, issn = {2397-334X}, abstract = {Ediacaran fossil communities consist of the oldest macroscopic eukaryotic organisms. Increased size (height) is hypothesized to be driven by competition for water column resources, leading to vertical/epifaunal tiering and morphological innovations such as stems. Using spatial analyses, we find no correlation between tiering and resource competition, and that stemmed organisms are not tiered. Instead, we find that height is correlated with greater offspring dispersal, demonstrating the importance of colonization potential over resource competition.}, } @article {pmid29942021, year = {2018}, author = {Doering, GN and Scharf, I and Moeller, HV and Pruitt, JN}, title = {Social tipping points in animal societies in response to heat stress.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1298-1305}, doi = {10.1038/s41559-018-0592-5}, pmid = {29942021}, issn = {2397-334X}, abstract = {Living systems sometimes experience abrupt tipping points in response to stress. Here we investigate the factors contributing to the appearance of such abrupt state transitions in animal societies. We first construct a mathematical account of how the personality compositions of societies could alter their propensity to shift from calm to violent states in response to thermal stress. To evaluate our model, we subjected experimental societies of the spider Anelosimus studiosus to heat stress. We demonstrate that both colony size and personality composition influence the timing of and recoverability from sudden transitions in social state. Groups composed of aggressive personalities transitioned into violent within-group dynamics sooner during heating, and also resisted recovery to baseline non-aggressive behaviour during cooling. We further observed hysteresis in groups composed of aggressive individuals, where group behaviour depended strongly on whether the colony had previously been in a calm or agitated state. These results demonstrate that a society's susceptibility to sudden state shifts and their recoverability from them can be driven by the personalities of their constituents.}, } @article {pmid29942020, year = {2018}, author = {Sebé-Pedrós, A and Chomsky, E and Pang, K and Lara-Astiaso, D and Gaiti, F and Mukamel, Z and Amit, I and Hejnol, A and Degnan, BM and Tanay, A}, title = {Early metazoan cell type diversity and the evolution of multicellular gene regulation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1176-1188}, pmid = {29942020}, issn = {2397-334X}, support = {309706//European Research Council/International ; }, abstract = {A hallmark of metazoan evolution is the emergence of genomic mechanisms that implement cell-type-specific functions. However, the evolution of metazoan cell types and their underlying gene regulatory programmes remains largely uncharacterized. Here, we use whole-organism single-cell RNA sequencing to map cell-type-specific transcription in Porifera (sponges), Ctenophora (comb jellies) and Placozoa species. We describe the repertoires of cell types in these non-bilaterian animals, uncovering diverse instances of previously unknown molecular signatures, such as multiple types of peptidergic cells in Placozoa. Analysis of the regulatory programmes of these cell types reveals variable levels of complexity. In placozoans and poriferans, sequence motifs in the promoters are predictive of cell-type-specific programmes. By contrast, the generation of a higher diversity of cell types in ctenophores is associated with lower specificity of promoter sequences and the existence of distal regulatory elements. Our findings demonstrate that metazoan cell types can be defined by networks of transcription factors and proximal promoters, and indicate that further genome regulatory complexity may be required for more diverse cell type repertoires.}, } @article {pmid29942019, year = {2018}, author = {Constable, GWA and Kokko, H}, title = {The rate of facultative sex governs the number of expected mating types in isogamous species.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1168-1175}, doi = {10.1038/s41559-018-0580-9}, pmid = {29942019}, issn = {2397-334X}, abstract = {It is unclear why sexually reproducing isogamous species frequently contain just two self-incompatible mating types. Deterministic theory suggests that since rare novel mating types experience a selective advantage (by virtue of their many potential partners), the number of mating types should consistently grow. However, in nature, species with thousands of mating types are exceedingly rare. Several competing theories for the predominance of species with two mating types exist, yet they lack an explanation for how many are possible and in which species to expect high numbers. Here, we present a theoretical null model that explains the distribution of mating type numbers using just three biological parameters: mutation rate, population size and the rate of sex. If the number of mating types results from a mutation-extinction balance, the rate of sexual reproduction plays a crucial role. If sex is facultative and rare (a very common combination in isogamous species), mating type diversity will remain low. In this rare sex regime, small fitness differences between the mating types lead to more frequent extinctions, further lowering mating type diversity. We also show that the empirical literature supports the role of drift and facultativeness of sex as a determinant of mating type dynamics.}, } @article {pmid29942018, year = {2018}, author = {Hoffmann, DL and Standish, CD and Pike, AWG and García-Diez, M and Pettitt, PB and Angelucci, DE and Villaverde, V and Zapata, J and Milton, JA and Alcolea-González, J and Cantalejo-Duarte, P and Collado, H and de Balbín, R and Lorblanchet, M and Ramos-Muñoz, J and Weniger, GC and Zilhão, J}, title = {Dates for Neanderthal art and symbolic behaviour are reliable.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1044-1045}, doi = {10.1038/s41559-018-0598-z}, pmid = {29942018}, issn = {2397-334X}, } @article {pmid29942017, year = {2018}, author = {Milks, A}, title = {Making an impact.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1057-1058}, doi = {10.1038/s41559-018-0600-9}, pmid = {29942017}, issn = {2397-334X}, } @article {pmid29942016, year = {2018}, author = {Magid, K and Chatterton, RT and Ahamed, FU and Bentley, GR}, title = {Childhood ecology influences salivary testosterone, pubertal age and stature of Bangladeshi UK migrant men.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1146-1154}, doi = {10.1038/s41559-018-0567-6}, pmid = {29942016}, issn = {2397-334X}, abstract = {Male reproductive investment is energetically costly, and measures of human reproductive steroid hormones (testosterone), developmental tempo (pubertal timing) and growth (stature) correlate with local ecologies at the population level. It is unclear whether male reproductive investment in later life is 'set' during childhood development, mediated through adulthood, or varies by ethnicity. Applying a life-course model to Bangladeshi migrants to the United Kingdom, here we investigate plasticity in human male reproductive function resulting from childhood developmental conditions. We hypothesized that childhood ecology shapes adult trade-offs between reproductive investment and/or other fitness-related traits. We predicted correspondence between these traits and developmental timing of exposure to ecological constraints (Bangladesh) or conditions of surplus (United Kingdom). We compared: Bangladesh sedentees (n = 107); Bangladeshi men who migrated in childhood to the United Kingdom (n = 59); migrants who arrived in adulthood (n = 75); second-generation UK-born and raised children of Bangladeshi migrants (n = 56); and UK-born ethnic Europeans (n = 62). Migration before puberty predicted higher testosterone and an earlier recalled pubertal age compared with Bangladeshi sedentees or adult migrants, with more pronounced differences in men who arrived before the age of eight. Second-generation Bangladeshis were taller, with higher testosterone than sedentees and adult migrants, and higher waking testosterone than Europeans. Age-related testosterone profiles varied by group, declining in UK migrants, increasing in sedentees, and having no significant relationship within UK-born groups. We conclude that male reproductive function apparently remains plastic late into childhood, is independent of Bengali or European ethnicity, and shapes physiological trade-offs later in life.}, } @article {pmid29942015, year = {2018}, author = {Blackwell, AD}, title = {Childhood conditions set the balance.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1061-1062}, doi = {10.1038/s41559-018-0594-3}, pmid = {29942015}, issn = {2397-334X}, } @article {pmid29942014, year = {2018}, author = {Phadke, SS}, title = {Sex begets sexes.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1063-1064}, doi = {10.1038/s41559-018-0597-0}, pmid = {29942014}, issn = {2397-334X}, } @article {pmid29942013, year = {2018}, author = {}, title = {Making connections.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1041}, doi = {10.1038/s41559-018-0604-5}, pmid = {29942013}, issn = {2397-334X}, } @article {pmid29942012, year = {2018}, author = {Gaudzinski-Windheuser, S and Noack, ES and Pop, E and Herbst, C and Pfleging, J and Buchli, J and Jacob, A and Enzmann, F and Kindler, L and Iovita, R and Street, M and Roebroeks, W}, title = {Evidence for close-range hunting by last interglacial Neanderthals.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1087-1092}, doi = {10.1038/s41559-018-0596-1}, pmid = {29942012}, issn = {2397-334X}, abstract = {Animal resources have been part of hominin diets since around 2.5 million years ago, with sharp-edged stone tools facilitating access to carcasses. How exactly hominins acquired animal prey and how hunting strategies varied through time and space is far from clear. The oldest possible hunting weapons known from the archaeological record are 300,000 to 400,000-year-old sharpened wooden staves. These may have been used as throwing and/or close-range thrusting spears, but actual data on how such objects were used are lacking, as unambiguous lesions caused by such weapon-like objects are unknown for most of human prehistory. Here, we report perforations observed on two fallow deer skeletons from Neumark-Nord, Germany, retrieved during excavations of 120,000-year-old lake shore deposits with abundant traces of Neanderthal presence. Detailed studies of the perforations, including micro-computed tomography imaging and ballistic experiments, demonstrate that they resulted from the close-range use of thrusting spears. Such confrontational ways of hunting require close cooperation between participants, and over time may have shaped important aspects of hominin biology and behaviour.}, } @article {pmid29941901, year = {2018}, author = {Löhr, JM}, title = {Weighing in on weight loss in pancreatic cancer.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {526-528}, doi = {10.1038/d41586-018-05424-2}, pmid = {29941901}, issn = {1476-4687}, mesh = {Adiposity ; Body Weight ; Cachexia ; Humans ; *Obesity ; Pancreatic Neoplasms ; *Weight Loss ; }, } @article {pmid29941900, year = {2018}, author = {Vespignani, A}, title = {Twenty years of network science.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {528-529}, doi = {10.1038/d41586-018-05444-y}, pmid = {29941900}, issn = {1476-4687}, mesh = {*Mathematics ; *Science ; }, } @article {pmid29941899, year = {2018}, author = {Semple, RK and Vanhaesebroeck, B}, title = {Lessons for cancer drug treatment from tackling a non-cancerous overgrowth syndrome.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {523-525}, doi = {10.1038/d41586-018-05365-w}, pmid = {29941899}, issn = {1476-4687}, mesh = {*Antineoplastic Agents ; Class I Phosphatidylinositol 3-Kinases ; Humans ; *Neoplasms ; Phosphatidylinositol 3-Kinases ; Syndrome ; }, } @article {pmid29941881, year = {2018}, author = {Impens, F and Rolhion, N and Radoshevich, L and Bécavin, C and Duval, M and Mellin, J and García Del Portillo, F and Pucciarelli, MG and Williams, AH and Cossart, P}, title = {Author Correction: N-terminomics identifies Prli42 as a membrane miniprotein conserved in Firmicutes and critical for stressosome activation in Listeria monocytogenes.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {962}, doi = {10.1038/s41564-018-0197-4}, pmid = {29941881}, issn = {2058-5276}, abstract = {This Article contains a URL for a publically available whole-genome browser (http://nterm.listeriomics.pasteur.fr). However, due to technical constraint, this website has been replaced with an alternative (https://listeriomics.pasteur.fr).}, } @article {pmid29941608, year = {2018}, author = {Yoshida, GJ}, title = {How to eliminate MYCN-positive hepatic cancer stem cells to prevent the recurrence?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6388-E6389}, pmid = {29941608}, issn = {1091-6490}, mesh = {Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; *N-Myc Proto-Oncogene Protein ; *Neoplasm Recurrence, Local ; Neoplastic Stem Cells ; Neuroblastoma/genetics ; }, } @article {pmid29941607, year = {2018}, author = {Qin, XY and Dohmae, N and Kojima, S}, title = {Reply to Yoshida: Liver cancer stem cells: Identification and lipid metabolic reprogramming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6390-E6391}, pmid = {29941607}, issn = {1091-6490}, mesh = {Cellular Reprogramming ; Humans ; Induced Pluripotent Stem Cells ; Lipids ; *Liver ; Neoplasms ; *Neoplastic Stem Cells ; }, } @article {pmid29941606, year = {2018}, author = {Ruggeri, FS and Benedetti, F and Knowles, TPJ and Lashuel, HA and Sekatskii, S and Dietler, G}, title = {Identification and nanomechanical characterization of the fundamental single-strand protofilaments of amyloid α-synuclein fibrils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7230-7235}, pmid = {29941606}, issn = {1091-6490}, support = {337969//European Research Council/International ; }, mesh = {Amyloid/*chemistry/metabolism/ultrastructure ; Humans ; Microscopy, Atomic Force ; Parkinson Disease/metabolism/therapy ; Protein Aggregation, Pathological/metabolism/pathology ; *Protein Unfolding ; alpha-Synuclein/*chemistry/metabolism ; }, abstract = {The formation and spreading of amyloid aggregates from the presynaptic protein α-synuclein in the brain play central roles in the pathogenesis of Parkinson's disease. Here, we use high-resolution atomic force microscopy to investigate the early oligomerization events of α-synuclein with single monomer angstrom resolution. We identify, visualize, and characterize directly the smallest elementary unit in the hierarchical assembly of amyloid fibrils, termed here single-strand protofilaments. We show that protofilaments form from the direct molecular assembly of unfolded monomeric α-synuclein polypeptide chains. To unravel protofilaments' internal structure and elastic properties, we manipulated nanomechanically these species by atomic force spectroscopy. The single-molecule scale identification and characterization of the fundamental unit of amyloid assemblies provide insights into early events underlying their formation and shed light on opportunities for therapeutic intervention at the early stages of aberrant protein self-assembly.}, } @article {pmid29941605, year = {2018}, author = {Born, D and Reuter, L and Mersdorf, U and Mueller, M and Fischer, MG and Meinhart, A and Reinstein, J}, title = {Capsid protein structure, self-assembly, and processing reveal morphogenesis of the marine virophage mavirus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7332-7337}, pmid = {29941605}, issn = {1091-6490}, mesh = {*Capsid Proteins/chemistry/genetics/metabolism ; *Peptide Hydrolases/chemistry/genetics/metabolism ; *Virion/chemistry/genetics/metabolism ; *Virophages/chemistry/physiology ; Virus Assembly/*physiology ; }, abstract = {Virophages have the unique property of parasitizing giant viruses within unicellular hosts. Little is understood about how they form infectious virions in this tripartite interplay. We provide mechanistic insights into assembly and maturation of mavirus, a marine virophage, by combining structural and stability studies on capsomers, virus-like particles (VLPs), and native virions. We found that the mavirus protease processes the double jelly-roll (DJR) major capsid protein (MCP) at multiple C-terminal sites and that these sites are conserved among virophages. Mavirus MCP assembled in Escherichia coli in the absence and presence of penton protein, forming VLPs with defined size and shape. While quantifying VLPs in E. coli lysates, we found that full-length rather than processed MCP is the competent state for capsid assembly. Full-length MCP was thermally more labile than truncated MCP, and crystal structures of both states indicate that full-length MCP has an expanded DJR core. Thus, we propose that the MCP C-terminal domain serves as a scaffolding domain by adding strain on MCP to confer assembly competence. Mavirus protease processed MCP more efficiently after capsid assembly, which provides a regulation mechanism for timing capsid maturation. By analogy to Sputnik and adenovirus, we propose that MCP processing renders mavirus particles infection competent by loosening interactions between genome and capsid shell and destabilizing pentons for genome release into host cells. The high structural similarity of mavirus and Sputnik capsid proteins together with conservation of protease and MCP processing suggest that assembly and maturation mechanisms described here are universal for virophages.}, } @article {pmid29941604, year = {2018}, author = {Sun, L and Lin, H and Kohlstedt, KL and Schatz, GC and Mirkin, CA}, title = {Design principles for photonic crystals based on plasmonic nanoparticle superlattices.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7242-7247}, pmid = {29941604}, issn = {1091-6490}, abstract = {Photonic crystals have been widely studied due to their broad technological applications in lasers, sensors, optical telecommunications, and display devices. Typically, photonic crystals are periodic structures of touching dielectric materials with alternating high and low refractive indices, and to date, the variables of interest have focused primarily on crystal symmetry and the refractive indices of the constituent materials, primarily polymers and semiconductors. In contrast, finite difference time domain (FDTD) simulations suggest that plasmonic nanoparticle superlattices with spacer groups offer an alternative route to photonic crystals due to the controllable spacing of the nanoparticles and the high refractive index of the lattices, even far away from the plasmon frequency where losses are low. Herein, the stopband features of 13 Bravais lattices are characterized and compared, resulting in paradigm-shifting design principles for photonic crystals. Based on these design rules, a simple cubic structure with an ∼130-nm lattice parameter is predicted to have a broad photonic stopband, a property confirmed by synthesizing the structure via DNA programmable assembly and characterizing it by reflectance measurements. We show through simulation that a maximum reflectance of more than 0.99 can be achieved in these plasmonic photonic crystals by optimizing the nanoparticle composition and structural parameters.}, } @article {pmid29941603, year = {2018}, author = {Wang, B and Li, D and Kovalchuk, I and Apel, IJ and Chinnaiyan, AM and Wóycicki, RK and Cantor, CR and Kovalchuk, O}, title = {miR-34a directly targets tRNAiMet precursors and affects cellular proliferation, cell cycle, and apoptosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7392-7397}, pmid = {29941603}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {*Apoptosis ; Argonaute Proteins/genetics/metabolism ; Breast Neoplasms/genetics/*metabolism/pathology ; Cell Cycle ; Female ; *Gene Expression Regulation, Neoplastic ; Humans ; MCF-7 Cells ; MicroRNAs/*biosynthesis/genetics ; Neoplasm Proteins/genetics/metabolism ; RNA Precursors/*biosynthesis/genetics ; *RNA Processing, Post-Transcriptional ; RNA, Neoplasm/*biosynthesis/genetics ; RNA, Transfer, Met/*biosynthesis/genetics ; }, abstract = {It remains unknown whether microRNA (miRNA/miR) can target transfer RNA (tRNA) molecules. Here we provide evidence that miR-34a physically interacts with and functionally targets tRNAiMet precursors in both in vitro pulldown and Argonaute 2 (AGO2) cleavage assays. We find that miR-34a suppresses breast carcinogenesis, at least in part by lowering the levels of tRNAiMet through AGO2-mediated repression, consequently inhibiting the proliferation of breast cancer cells and inducing cell cycle arrest and apoptosis. Moreover, miR-34a expression is negatively correlated with tRNAiMet levels in cancer cell lines. Furthermore, we find that tRNAiMet knockdown also reduces cell proliferation while inducing cell cycle arrest and apoptosis. Conversely, ectopic expression of tRNAiMet promotes cell proliferation, inhibits apoptosis, and accelerates the S/G2 transition. Moreover, the enforced expression of modified tRNAiMet completely restores the phenotypic changes induced by miR-34a. Our results demonstrate that miR-34a directly targets tRNAiMet precursors via AGO2-mediated cleavage, and that tRNAiMet functions as an oncogene, potentially representing a target molecule for therapeutic intervention.}, } @article {pmid29941602, year = {2018}, author = {Hakanpaa, L and Kiss, EA and Jacquemet, G and Miinalainen, I and Lerche, M and Guzmán, C and Mervaala, E and Eklund, L and Ivaska, J and Saharinen, P}, title = {Targeting β1-integrin inhibits vascular leakage in endotoxemia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6467-E6476}, pmid = {29941602}, issn = {1091-6490}, mesh = {Animals ; Antigens, CD/genetics/metabolism ; Cadherins/genetics/metabolism ; Disease Models, Animal ; Endothelial Cells/*metabolism/pathology ; Endotoxemia/chemically induced/genetics/*metabolism/pathology ; Integrin alpha5beta1/genetics/metabolism ; Integrin beta1/genetics/*metabolism ; Intercellular Junctions/genetics/*metabolism/pathology ; Interleukin-1beta/genetics/metabolism ; Lipopolysaccharides/toxicity ; Mice ; Mice, Transgenic ; Protein Transport/drug effects/genetics ; Receptor, TIE-2/genetics/metabolism ; }, abstract = {Loss of endothelial integrity promotes capillary leakage in numerous diseases, including sepsis, but there are no effective therapies for preserving endothelial barrier function. Angiopoietin-2 (ANGPT2) is a context-dependent regulator of vascular leakage that signals via both endothelial TEK receptor tyrosine kinase (TIE2) and integrins. Here, we show that antibodies against β1-integrin decrease LPS-induced vascular leakage in murine endotoxemia, as either a preventative or an intervention therapy. β1-integrin inhibiting antibodies bound to the vascular endothelium in vivo improved the integrity of endothelial cell-cell junctions and protected mice from endotoxemia-associated cardiac failure, without affecting endothelial inflammation, serum proinflammatory cytokine levels, or TIE receptor signaling. Moreover, conditional deletion of a single allele of endothelial β1-integrin protected mice from LPS-induced vascular leakage. In endothelial monolayers, the inflammatory agents thrombin, lipopolysaccharide (LPS), and IL-1β decreased junctional vascular endothelial (VE)-cadherin and induced actin stress fibers via β1- and α5-integrins and ANGPT2. Additionally, β1-integrin inhibiting antibodies prevented inflammation-induced endothelial cell contractility and monolayer permeability. Mechanistically, the inflammatory agents stimulated ANGPT2-dependent translocation of α5β1-integrin into tensin-1-positive fibrillar adhesions, which destabilized the endothelial monolayer. Thus, β1-integrin promotes endothelial barrier disruption during inflammation, and targeting β1-integrin signaling could serve as a novel means of blocking pathological vascular leak.}, } @article {pmid29941601, year = {2018}, author = {Konrad, A and Flibotte, S and Taylor, J and Waterston, RH and Moerman, DG and Bergthorsson, U and Katju, V}, title = {Mutational and transcriptional landscape of spontaneous gene duplications and deletions in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7386-7391}, pmid = {29941601}, issn = {1091-6490}, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Caenorhabditis elegans/genetics/metabolism ; *Gene Deletion ; *Gene Dosage ; *Gene Duplication ; Genome-Wide Association Study ; *Transcription, Genetic ; }, abstract = {Gene duplication and deletion are pivotal processes shaping the structural and functional repertoire of genomes, with implications for disease, adaptation, and evolution. We employed a mutation accumulation (MA) framework partnered with high-throughput genomics to assess the molecular and transcriptional characteristics of newly arisen gene copy-number variants (CNVs) in Caenorhabditis elegans populations subjected to varying intensity of selection. Here, we report a direct spontaneous genome-wide rate of gene duplication of 2.9 × 10-5/gene per generation in C. elegans, the highest for any species to date. The rate of gene deletion is sixfold lower (5 × 10-6/gene per generation). Deletions of highly expressed genes are particularly deleterious, given their paucity in even the N = 1 lines with minimal efficacy of selection. The increase in average transcript abundance of new duplicates arising under minimal selection is significantly greater than twofold compared with single copies of the same gene, suggesting that genes in segmental duplications are frequently overactive at inception. The average increase in transcriptional activity of gene duplicates is greater in the N = 1 MA lines than in MA lines with larger population bottlenecks. There is an inverse relationship between the ancestral transcription levels of new gene duplicates and population size, with duplicate copies of highly expressed genes less likely to accumulate in larger populations. Our results demonstrate a fitness cost of increased transcription following duplication, which results in purifying selection against new gene duplicates. However, on average, duplications also provide a significant increase in gene expression that can facilitate adaptation to novel environmental challenges.}, } @article {pmid29941600, year = {2018}, author = {Pacella, I and Procaccini, C and Focaccetti, C and Miacci, S and Timperi, E and Faicchia, D and Severa, M and Rizzo, F and Coccia, EM and Bonacina, F and Mitro, N and Norata, GD and Rossetti, G and Ranzani, V and Pagani, M and Giorda, E and Wei, Y and Matarese, G and Barnaba, V and Piconese, S}, title = {Fatty acid metabolism complements glycolysis in the selective regulatory T cell expansion during tumor growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6546-E6555}, pmid = {29941600}, issn = {1091-6490}, support = {310496//European Research Council/International ; }, mesh = {Animals ; Cell Line, Tumor ; Fatty Acid Synthase, Type I/genetics/immunology ; Fatty Acids/genetics/*immunology ; Glycolysis/*immunology ; Humans ; Mice ; Mice, Transgenic ; Neoplasm Proteins/genetics/immunology ; Neoplasms, Experimental/genetics/*immunology/pathology ; Oxidation-Reduction ; T-Lymphocytes, Regulatory/*immunology/pathology ; Tumor Microenvironment/genetics/*immunology ; }, abstract = {The tumor microenvironment restrains conventional T cell (Tconv) activation while facilitating the expansion of Tregs. Here we showed that Tregs' advantage in the tumor milieu relies on supplemental energetic routes involving lipid metabolism. In murine models, tumor-infiltrating Tregs displayed intracellular lipid accumulation, which was attributable to an increased rate of fatty acid (FA) synthesis. Since the relative advantage in glucose uptake may fuel FA synthesis in intratumoral Tregs, we demonstrated that both glycolytic and oxidative metabolism contribute to Tregs' expansion. We corroborated our data in human tumors showing that Tregs displayed a gene signature oriented toward glycolysis and lipid synthesis. Our data support a model in which signals from the tumor microenvironment induce a circuitry of glycolysis, FA synthesis, and oxidation that confers a preferential proliferative advantage to Tregs, whose targeting might represent a strategy for cancer treatment.}, } @article {pmid29941599, year = {2018}, author = {Lo, PW and Shie, JJ and Chen, CH and Wu, CY and Hsu, TL and Wong, CH}, title = {O-GlcNAcylation regulates the stability and enzymatic activity of the histone methyltransferase EZH2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7302-7307}, pmid = {29941599}, issn = {1091-6490}, mesh = {Acetylglucosamine/chemistry/genetics/*metabolism ; Amino Acid Substitution ; Cell Line ; Enhancer of Zeste Homolog 2 Protein/chemistry/genetics/*metabolism ; Enzyme Stability ; Glycosylation ; Humans ; *Mutation, Missense ; Protein Domains ; }, abstract = {Protein O-glycosylation by attachment of β-N-acetylglucosamine (GlcNAc) to the Ser or Thr residue is a major posttranslational glycosylation event and is often associated with protein folding, stability, and activity. The methylation of histone H3 at Lys-27 catalyzed by the methyltransferase EZH2 was known to suppress gene expression and cancer development, and we previously reported that the O-GlcNAcylation of EZH2 at S76 stabilized EZH2 and facilitated the formation of H3K27me3 to inhibit tumor suppression. In this study, we employed a fluorescence-based method of sugar labeling combined with mass spectrometry to investigate EZH2 glycosylation and identified five O-GlcNAcylation sites. We also find that mutation of one or more of the O-GlcNAcylation sites S73A, S76A, S84A, and T313A in the N-terminal region decreases the stability of EZH2, but does not affect its association with the PRC2 components SUZ12 and EED. Mutation of the C-terminal O-GlcNAcylation site (S729A) in the catalytic domain of EZH2 abolishes the di- and trimethylation activities, but not the monomethylation of H3K27, nor the integrity of the PRC2/EZH2 core complex. Our results show the effect of individual O-GlcNAcylation sites on the function of EZH2 and suggest an alternative approach to tumor suppression through selective inhibition of EZH2 O-GlcNAcylation.}, } @article {pmid29941598, year = {2018}, author = {Clark, RR and Judd, J and Lasek-Nesselquist, E and Montgomery, SA and Hoffmann, JG and Derbyshire, KM and Gray, TA}, title = {Direct cell-cell contact activates SigM to express the ESX-4 secretion system in Mycobacterium smegmatis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6595-E6603}, pmid = {29941598}, issn = {1091-6490}, support = {R21 AI119427/AI/NIAID NIH HHS/United States ; }, mesh = {*Bacterial Proteins/genetics/metabolism ; Conjugation, Genetic/*physiology ; Gene Expression Regulation, Bacterial/*physiology ; Gene Regulatory Networks/physiology ; *Mycobacterium smegmatis/genetics/metabolism ; *Transcription Factors/genetics/metabolism ; *Type IV Secretion Systems/genetics/metabolism ; *Type VII Secretion Systems/genetics/metabolism ; }, abstract = {Conjugal cell-cell contact between strains of Mycobacterium smegmatis induces the esxUT transcript, which encodes the putative primary substrates of the ESAT-6 secretion system 4 (ESX-4) secretion system. This recipient response was required for conjugal transfer of chromosomal DNA from the donor strain. Here we show that the extracytoplasmic σ factor, SigM, is a cell contact-dependent activator of ESX-4 expression and is required for conjugal transfer of DNA in the recipient strain. The SigM regulon includes genes outside the seven-gene core esx4 locus that we show are also required for conjugation, and we show that some of these SigM-induced proteins likely function through ESX-4. A fluorescent reporter revealed that SigM is specifically activated in recipient cells in direct contact with donor cells. Coculture RNA-seq experiments indicated that SigM regulon induction occurred early and before transconjugants are detected. This work supports a model wherein donor contact with the recipient cell surface inactivates the transmembrane anti-SigM, thereby releasing SigM. Free SigM induces an extended ESX-4 secretion system, resulting in changes that facilitate chromosomal transfer. The contact-dependent inactivation of an extracytoplasmic σ-factor that tightly controls ESX-4 activity suggests a mechanism dedicated to detect, and appropriately respond to, external stimuli from mycobacteria.}, } @article {pmid29941597, year = {2018}, author = {Johnson, B and Leek, AN and Solé, L and Maverick, EE and Levine, TP and Tamkun, MM}, title = {Kv2 potassium channels form endoplasmic reticulum/plasma membrane junctions via interaction with VAPA and VAPB.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7331-E7340}, pmid = {29941597}, issn = {1091-6490}, support = {R01 GM109888/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biotinylation ; Cell Membrane/*chemistry ; Endoplasmic Reticulum/*chemistry ; HEK293 Cells ; Hippocampus/metabolism ; Humans ; Protein Transport ; Rats ; Shab Potassium Channels/*chemistry/physiology ; Vesicular Transport Proteins/*chemistry/metabolism ; }, abstract = {Kv2.1 exhibits two distinct forms of localization patterns on the neuronal plasma membrane: One population is freely diffusive and regulates electrical activity via voltage-dependent K+ conductance while a second one localizes to micrometer-sized clusters that contain densely packed, but nonconducting, channels. We have previously established that these clusters represent endoplasmic reticulum/plasma membrane (ER/PM) junctions that function as membrane trafficking hubs and that Kv2.1 plays a structural role in forming these membrane contact sites in both primary neuronal cultures and transfected HEK cells. Clustering and the formation of ER/PM contacts are regulated by phosphorylation within the channel C terminus, offering cells fast, dynamic control over the physical relationship between the cortical ER and PM. The present study addresses the mechanisms by which Kv2.1 and the related Kv2.2 channel interact with the ER membrane. Using proximity-based biotinylation techniques in transfected HEK cells we identified ER VAMP-associated proteins (VAPs) as potential Kv2.1 interactors. Confirmation that Kv2.1 and -2.2 bind VAPA and VAPB employed colocalization/redistribution, siRNA knockdown, and Förster resonance energy transfer (FRET)-based assays. CD4 chimeras containing sequence from the Kv2.1 C terminus were used to identify a noncanonical VAP-binding motif. VAPs were first identified as proteins required for neurotransmitter release in Aplysia and are now known to be abundant scaffolding proteins involved in membrane contact site formation throughout the ER. The VAP interactome includes AKAPs, kinases, membrane trafficking machinery, and proteins regulating nonvesicular lipid transport from the ER to the PM. Therefore, the Kv2-induced VAP concentration at ER/PM contact sites is predicted to have wide-ranging effects on neuronal cell biology.}, } @article {pmid29941596, year = {2018}, author = {Gould, JM and Smith, PJ and Airey, CJ and Mort, EJ and Airey, LE and Warricker, FDM and Pearson-Farr, JE and Weston, EC and Gould, PJW and Semmence, OG and Restall, KL and Watts, JA and McHugh, PC and Smith, SJ and Dewing, JM and Fleming, TP and Willaime-Morawek, S}, title = {Mouse maternal protein restriction during preimplantation alone permanently alters brain neuron proportion and adult short-term memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {31}, pages = {E7398-E7407}, pmid = {29941596}, issn = {1091-6490}, support = {BB/F007450/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I001840/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Apoptosis ; Brain/*embryology/pathology ; Cell Differentiation ; Cell Proliferation ; *Diet, Protein-Restricted ; Female ; *Maternal Nutritional Physiological Phenomena ; *Memory, Short-Term ; Mice ; Neural Stem Cells/*pathology ; *Neurogenesis ; }, abstract = {Maternal protein malnutrition throughout pregnancy and lactation compromises brain development in late gestation and after birth, affecting structural, biochemical, and pathway dynamics with lasting consequences for motor and cognitive function. However, the importance of nutrition during the preimplantation period for brain development is unknown. We have previously shown that maternal low-protein diet (LPD) confined to the preimplantation period (Emb-LPD) in mice, with normal nutrition thereafter, is sufficient to induce cardiometabolic and locomotory behavioral abnormalities in adult offspring. Here, using a range of in vivo and in vitro techniques, we report that Emb-LPD and sustained LPD reduce neural stem cell (NSC) and progenitor cell numbers at E12.5, E14.5, and E17.5 through suppressed proliferation rates in both ganglionic eminences and cortex of the fetal brain. Moreover, Emb-LPD causes remaining NSCs to up-regulate the neuronal differentiation rate beyond control levels, whereas in LPD, apoptosis increases to possibly temper neuron formation. Furthermore, Emb-LPD adult offspring maintain the increase in neuron proportion in the cortex, display increased cortex thickness, and exhibit short-term memory deficit analyzed by the novel-object recognition assay. Last, we identify altered expression of fragile X family genes as a potential molecular mechanism for adverse programming of brain development. Collectively, these data demonstrate that poor maternal nutrition from conception is sufficient to cause abnormal brain development and adult memory loss.}, } @article {pmid29941595, year = {2018}, author = {Romanov, E and Gavish, M}, title = {Near-optimal matrix recovery from random linear measurements.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7200-7205}, pmid = {29941595}, issn = {1091-6490}, abstract = {In matrix recovery from random linear measurements, one is interested in recovering an unknown M-by-N matrix [Formula: see text] from [Formula: see text] measurements [Formula: see text], where each [Formula: see text] is an M-by-N measurement matrix with i.i.d. random entries, [Formula: see text] We present a matrix recovery algorithm, based on approximate message passing, which iteratively applies an optimal singular-value shrinker-a nonconvex nonlinearity tailored specifically for matrix estimation. Our algorithm typically converges exponentially fast, offering a significant speedup over previously suggested matrix recovery algorithms, such as iterative solvers for nuclear norm minimization (NNM). It is well known that there is a recovery tradeoff between the information content of the object [Formula: see text] to be recovered (specifically, its matrix rank r) and the number of linear measurements n from which recovery is to be attempted. The precise tradeoff between r and n, beyond which recovery by a given algorithm becomes possible, traces the so-called phase transition curve of that algorithm in the [Formula: see text] plane. The phase transition curve of our algorithm is noticeably better than that of NNM. Interestingly, it is close to the information-theoretic lower bound for the minimal number of measurements needed for matrix recovery, making it not only state of the art in terms of convergence rate, but also near optimal in terms of the matrices it successfully recovers.}, } @article {pmid29941594, year = {2018}, author = {Li, L and Duan, Z and Li, H and Zhu, C and Henkelman, G and Francisco, JS and Zeng, XC}, title = {Formation of HONO from the NH3-promoted hydrolysis of NO2 dimers in the atmosphere.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7236-7241}, pmid = {29941594}, issn = {1091-6490}, abstract = {One challenging issue in atmospheric chemistry is identifying the source of nitrous acid (HONO), which is believed to be a primary source of atmospheric "detergent" OH radicals. Herein, we show a reaction route for the formation of HONO species from the NH3-promoted hydrolysis of a NO2 dimer (ONONO2), which entails a low free-energy barrier of 0.5 kcal/mol at room temperature. Our systematic study of HONO formation based on NH3 + ONONO2 + nH2O and water droplet systems with the metadynamics simulation method and a reaction pathway searching method reveals two distinct mechanisms: (i) In monohydrates (n = 1), tetrahydrates (n = 4), and water droplets, only one water molecule is directly involved in the reaction (denoted the single-water mechanism); and (ii) the splitting of two neighboring water molecules is seen in the dihydrates (n = 2) and trihydrates (n = 3) (denoted the dual-water mechanism). A comparison of the computed free-energy surface for NH3-free and NH3-containing systems indicates that gaseous NH3 can markedly lower the free-energy barrier to HONO formation while stabilizing the product state, producing a more exergonic reaction, in contrast to the endergonic reaction for the NH3-free system. More importantly, the water droplet reduces the free-energy barrier for HONO formation to 0.5 kcal/mol, which is negligible at room temperature. We show that the entropic contribution is important in the mechanism by which NH3 promotes HONO formation. This study provides insight into the importance of fundamental HONO chemistry and its broader implication to aerosol and cloud processing chemistry at the air-water interface.}, } @article {pmid29941593, year = {2018}, author = {Bart, SM and Cohen, C and Dye, JM and Shorter, J and Bates, P}, title = {Enhancement of Ebola virus infection by seminal amyloid fibrils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7410-7415}, pmid = {29941593}, issn = {1091-6490}, support = {P30 CA016520/CA/NCI NIH HHS/United States ; R21 HD074510/HD/NICHD NIH HHS/United States ; T32 AI007324/AI/NIAID NIH HHS/United States ; }, mesh = {Amyloid/genetics/*metabolism ; Ebolavirus/genetics/*metabolism ; Female ; Glycoproteins/genetics/*metabolism ; HeLa Cells ; Hemorrhagic Fever, Ebola/genetics/*metabolism/*transmission ; Humans ; Male ; Seminal Plasma Proteins/genetics/*metabolism ; Viral Proteins/genetics/*metabolism ; }, abstract = {The 2014 western Africa Ebola virus (EBOV) epidemic was unprecedented in magnitude, infecting over 28,000 and causing over 11,000 deaths. During this outbreak, multiple instances of EBOV sexual transmission were reported, including cases where the infectious individual had recovered from EBOV disease months before transmission. Potential human host factors in EBOV sexual transmission remain unstudied. Several basic seminal amyloids, most notably semen-derived enhancer of viral infection (SEVI), enhance in vitro infection by HIV and several other viruses. To test the ability of these peptides to enhance EBOV infection, viruses bearing the EBOV glycoprotein (EboGP) were preincubated with physiological concentrations of SEVI before infection of physiologically relevant cell lines and primary cells. Preincubation with SEVI significantly increased EboGP-mediated infectivity and replication in epithelium- and monocyte-derived cell lines. This enhancement was dependent upon amyloidogenesis and positive charge, and infection results were observed with both viruses carrying EboGP and authentic EBOV as well as with semen. SEVI enhanced binding of virus to cells and markedly increased its subsequent internalization. SEVI also stimulated uptake of a fluid phase marker by macropinocytosis, a critical mechanism by which cells internalize EBOV. We report a previously unrecognized ability of SEVI and semen to significantly alter viral physical properties critical for transmissibility by increasing the stability of EboGP-bearing recombinant viruses during incubation at elevated temperature and providing resistance to desiccation. Given the potential for EBOV sexual transmission to spark new transmission chains, these findings represent an important interrogation of factors potentially important for this EBOV transmission route.}, } @article {pmid29941592, year = {2018}, author = {Scales, KL and Hazen, EL and Jacox, MG and Castruccio, F and Maxwell, SM and Lewison, RL and Bograd, SJ}, title = {Fisheries bycatch risk to marine megafauna is intensified in Lagrangian coherent structures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7362-7367}, pmid = {29941592}, issn = {1091-6490}, mesh = {Animals ; Aquatic Organisms/*physiology ; *Ecosystem ; *Fisheries ; Fishes/*physiology ; *Models, Biological ; *Oceans and Seas ; }, abstract = {Incidental catch of nontarget species (bycatch) is a major barrier to ecological and economic sustainability in marine capture fisheries. Key to mitigating bycatch is an understanding of the habitat requirements of target and nontarget species and the influence of heterogeneity and variability in the dynamic marine environment. While patterns of overlap among marine capture fisheries and habitats of a taxonomically diverse range of marine vertebrates have been reported, a mechanistic understanding of the real-time physical drivers of bycatch events is lacking. Moving from describing patterns toward understanding processes, we apply a Lagrangian analysis to a high-resolution ocean model output to elucidate the fundamental mechanisms that drive fisheries interactions. We find that the likelihood of marine megafauna bycatch is intensified in attracting Lagrangian coherent structures associated with submesoscale and mesoscale filaments, fronts, and eddies. These results highlight how the real-time tracking of dynamic structures in the oceans can support fisheries sustainability and advance ecosystem-based management.}, } @article {pmid29941591, year = {2018}, author = {Boutanaev, AM and Osbourn, AE}, title = {Multigenome analysis implicates miniature inverted-repeat transposable elements (MITEs) in metabolic diversification in eudicots.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6650-E6658}, pmid = {29941591}, issn = {1091-6490}, support = {BB/P012523/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Aquilegia/*genetics ; *Genome, Plant ; *Inverted Repeat Sequences ; Kalanchoe/*genetics ; *Multigene Family ; }, abstract = {Plants produce a plethora of natural products, including many drugs. It has recently emerged that the genes encoding different natural product pathways may be organized as biosynthetic gene clusters in plant genomes, with >30 examples reported so far. Despite superficial similarities with microbes, these clusters have not arisen by horizontal gene transfer, but rather by gene duplication, neofunctionalization, and relocation via unknown mechanisms. Previously we reported that two Arabidopsis thaliana biosynthetic gene clusters are located in regions of the genome that are significantly enriched in transposable elements (TEs). Other plant biosynthetic gene clusters also harbor abundant TEs. TEs can mediate genomic rearrangement by providing homologous sequences that enable illegitimate recombination and gene relocation. Thus, TE-mediated recombination may contribute to plant biosynthetic gene cluster formation. TEs may also facilitate establishment of regulons. However, a systematic analysis of the TEs associated with plant biosynthetic gene clusters has not been carried out. Here we investigate the TEs associated with clustered terpene biosynthetic genes in multiple plant genomes and find evidence to suggest a role for miniature inverted-repeat transposable elements in cluster formation in eudicots. Through investigation of the newly sequenced Amborella trichopoda, Aquilegia coerulea, and Kalanchoe fedtschenkoi genomes, we further show that the "block" mechanism of founding of biosynthetic gene clusters through duplication and diversification of pairs of terpene synthase and cytochrome P450 genes that is prevalent in the eudicots arose around 90-130 million years ago, after the appearance of the basal eudicots and before the emergence of the superrosid clade.}, } @article {pmid29941590, year = {2018}, author = {Konovalova, A and Grabowicz, M and Balibar, CJ and Malinverni, JC and Painter, RE and Riley, D and Mann, PA and Wang, H and Garlisi, CG and Sherborne, B and Rigel, NW and Ricci, DP and Black, TA and Roemer, T and Silhavy, TJ and Walker, SS}, title = {Inhibitor of intramembrane protease RseP blocks the σE response causing lethal accumulation of unfolded outer membrane proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6614-E6621}, pmid = {29941590}, issn = {1091-6490}, mesh = {*Bacterial Outer Membrane Proteins/genetics/metabolism ; *Endopeptidases/genetics/metabolism ; *Escherichia coli/genetics/metabolism ; *Escherichia coli Proteins/genetics/metabolism ; *Membrane Proteins/genetics/metabolism ; *Protein Unfolding ; *Transcription Factors/metabolism ; }, abstract = {The outer membrane (OM) of Gram-negative bacteria forms a robust permeability barrier that blocks entry of toxins and antibiotics. Most OM proteins (OMPs) assume a β-barrel fold, and some form aqueous channels for nutrient uptake and efflux of intracellular toxins. The Bam machine catalyzes rapid folding and assembly of OMPs. Fidelity of OMP biogenesis is monitored by the σE stress response. When OMP folding defects arise, the proteases DegS and RseP act sequentially to liberate σE into the cytosol, enabling it to activate transcription of the stress regulon. Here, we identify batimastat as a selective inhibitor of RseP that causes a lethal decrease in σE activity in Escherichia coli, and we further identify RseP mutants that are insensitive to inhibition and confer resistance. Remarkably, batimastat treatment allows the capture of elusive intermediates in the OMP biogenesis pathway and offers opportunities to better understand the underlying basis for σE essentiality.}, } @article {pmid29941589, year = {2018}, author = {Watanabe, Y and Raghwani, J and Allen, JD and Seabright, GE and Li, S and Moser, F and Huiskonen, JT and Strecker, T and Bowden, TA and Crispin, M}, title = {Structure of the Lassa virus glycan shield provides a model for immunological resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7320-7325}, pmid = {29941589}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MR/L009528/1//Medical Research Council/United Kingdom ; MR/N002091/1//Medical Research Council/United Kingdom ; UM1 AI100663/AI/NIAID NIH HHS/United States ; 203141/Z/16/Z//Wellcome Trust/United Kingdom ; 060208/Z/00/Z//Wellcome Trust/United Kingdom ; 093305/Z/10/Z//Wellcome Trust/United Kingdom ; 107652/Z15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Glycosylation ; Lassa virus/*chemistry/immunology ; Oligosaccharides/*chemistry/immunology ; Viral Envelope Proteins/*chemistry/immunology ; }, abstract = {Lassa virus is an Old World arenavirus endemic to West Africa that causes severe hemorrhagic fever. Vaccine development has focused on the envelope glycoprotein complex (GPC) that extends from the virion envelope. The often inadequate antibody immune response elicited by both vaccine and natural infection has been, in part, attributed to the abundance of N-linked glycosylation on the GPC. Here, using a virus-like-particle system that presents Lassa virus GPC in a native-like context, we determine the composite population of each of the N-linked glycosylation sites presented on the trimeric GPC spike. Our analysis reveals the presence of underprocessed oligomannose-type glycans, which form punctuated clusters that obscure the proteinous surface of both the GP1 attachment and GP2 fusion glycoprotein subunits of the Lassa virus GPC. These oligomannose clusters are seemingly derived as a result of sterically reduced accessibility to glycan processing enzymes, and limited amino acid diversification around these sites supports their role protecting against the humoral immune response. Combined, our data provide a structure-based blueprint for understanding how glycans render the glycoprotein spikes of Lassa virus and other Old World arenaviruses immunologically resistant targets.}, } @article {pmid29941588, year = {2018}, author = {}, title = {Correction to Supporting Information for Rashidian et al., Noninvasive imaging of immune responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6387}, doi = {10.1073/pnas.1809460115}, pmid = {29941588}, issn = {1091-6490}, } @article {pmid29941587, year = {2018}, author = {Onishi, M and Pecani, K and Jones, T and Pringle, JR and Cross, FR}, title = {F-actin homeostasis through transcriptional regulation and proteasome-mediated proteolysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6487-E6496}, pmid = {29941587}, issn = {1091-6490}, support = {R01 GM078153/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/*biosynthesis/genetics ; Chlamydomonas reinhardtii/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; Proteasome Endopeptidase Complex/genetics/*metabolism ; *Proteolysis ; *Transcription, Genetic ; }, abstract = {Many organisms possess multiple and often divergent actins whose regulation and roles are not understood in detail. For example, Chlamydomonas reinhardtii has both a conventional actin (IDA5) and a highly divergent one (NAP1); only IDA5 is expressed in normal proliferating cells. We showed previously that the drug latrunculin B (LatB) causes loss of filamentous (F-) IDA5 and strong up-regulation of NAP1, which then provides essential actin function(s) by forming LatB-resistant F-NAP1. RNA-sequencing analyses now show that this up-regulation of NAP1 reflects a broad transcriptional response, much of which depends on three proteins (LAT1, LAT2, and LAT3) identified previously as essential for NAP1 transcription. Many of the LAT-regulated genes contain a putative cis-acting regulatory site, the "LRE motif." The LatB transcriptional program appears to be activated by loss of F-IDA5 and deactivated by formation of F-NAP1, thus forming an F-actin-dependent negative-feedback loop. Multiple genes encoding proteins of the ubiquitin-proteasome system are among those induced by LatB, resulting in rapid degradation of IDA5 (but not NAP1). Our results suggest that IDA5 degradation is functionally important because nonpolymerizable LatB-bound IDA5 interferes with the formation of F-NAP1. The genes for the actin-interacting proteins cofilin and profilin are also induced. Cofilin induction may further the clearance of IDA5 by promoting the scission of F-IDA5, whereas profilin appears to function in protecting monomeric IDA5 from degradation. This multifaceted regulatory system allows rapid and quantitative turnover of F-actin in response to cytoskeletal perturbations and probably also maintains F-actin homeostasis under normal growth conditions.}, } @article {pmid29941586, year = {2018}, author = {}, title = {Correction for Lampert et al., Shear force-based genetic screen reveals negative regulators of cell adhesion and protrusive activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6670}, doi = {10.1073/pnas.1809927115}, pmid = {29941586}, issn = {1091-6490}, } @article {pmid29941585, year = {2018}, author = {Wang, X and Zhang, F and Su, R and Li, X and Chen, W and Chen, Q and Yang, T and Wang, J and Liu, H and Fang, Q and Cheng, L}, title = {Structure of RNA polymerase complex and genome within a dsRNA virus provides insights into the mechanisms of transcription and assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7344-7349}, pmid = {29941585}, issn = {1091-6490}, mesh = {Animals ; Capsid Proteins/*biosynthesis/genetics ; Carps ; Cell Line ; DNA-Directed RNA Polymerases/*metabolism ; *Genome, Viral ; RNA, Viral/*biosynthesis/genetics ; Reoviridae/*physiology ; Transcription, Genetic/*physiology ; Virus Assembly/*physiology ; }, abstract = {Most double-stranded RNA (dsRNA) viruses transcribe RNA plus strands within a common innermost capsid shell. This process requires coordinated efforts by RNA-dependent RNA polymerase (RdRp) together with other capsid proteins and genomic RNA. Here we report the near-atomic resolution structure of the RdRp protein VP2 in complex with its cofactor protein VP4 and genomic RNA within an aquareovirus capsid using 200-kV cryoelectron microscopy and symmetry-mismatch reconstruction. The structure of these capsid proteins enabled us to observe the elaborate nonicosahedral structure within the double-layered icosahedral capsid. Our structure shows that the RdRp complex is anchored at the inner surface of the capsid shell and interacts with genomic dsRNA and four of the five asymmetrically arranged N termini of the capsid shell proteins under the fivefold axis, implying roles for these N termini in virus assembly. The binding site of the RNA end at VP2 is different from the RNA cap binding site identified in the crystal structure of orthoreovirus RdRp λ3, although the structures of VP2 and λ3 are almost identical. A loop, which was thought to separate the RNA template and transcript, interacts with an apical domain of the capsid shell protein, suggesting a mechanism for regulating RdRp replication and transcription. A conserved nucleoside triphosphate binding site was localized in our RdRp cofactor protein VP4 structure, and interactions between the VP4 and the genomic RNA were identified.}, } @article {pmid29941584, year = {2018}, author = {Uphoff, S}, title = {Real-time dynamics of mutagenesis reveal the chronology of DNA repair and damage tolerance responses in single cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6516-E6525}, pmid = {29941584}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 101636/Z/13/Z//Wellcome Trust/United Kingdom ; 206159/Z/17/Z//Wellcome Trust/United Kingdom ; 206159/Z/17/B//Wellcome Trust/United Kingdom ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; DNA Mismatch Repair/*drug effects ; *DNA, Bacterial/genetics/metabolism ; *Escherichia coli/cytology/genetics/metabolism ; *Microfluidic Analytical Techniques ; Mutagenesis/*drug effects ; SOS Response (Genetics)/*drug effects ; }, abstract = {Evolutionary processes are driven by diverse molecular mechanisms that act in the creation and prevention of mutations. It remains unclear how these mechanisms are regulated because limitations of existing mutation assays have precluded measuring how mutation rates vary over time in single cells. Toward this goal, I detected nascent DNA mismatches as a proxy for mutagenesis and simultaneously followed gene expression dynamics in single Escherichia coli cells using microfluidics. This general microscopy-based approach revealed the real-time dynamics of mutagenesis in response to DNA alkylation damage and antibiotic treatments. It also enabled relating the creation of DNA mismatches to the chronology of the underlying molecular processes. By avoiding population averaging, I discovered cell-to-cell variation in mutagenesis that correlated with heterogeneity in the expression of alternative responses to DNA damage. Pulses of mutagenesis are shown to arise from transient DNA repair deficiency. Constitutive expression of DNA repair pathways and induction of damage tolerance by the SOS response compensate for delays in the activation of inducible DNA repair mechanisms, together providing robustness against the toxic and mutagenic effects of DNA alkylation damage.}, } @article {pmid29941583, year = {2018}, author = {}, title = {Correction for Smith et al., Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6385}, doi = {10.1073/pnas.1809742115}, pmid = {29941583}, issn = {1091-6490}, } @article {pmid29941582, year = {2018}, author = {Gabrielsen, P}, title = {QnAs with Gary A. Glatzmaier.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6880-6881}, pmid = {29941582}, issn = {1091-6490}, } @article {pmid29941581, year = {2018}, author = {Ueki, H and Wang, IH and Fukuyama, S and Katsura, H and da Silva Lopes, TJ and Neumann, G and Kawaoka, Y}, title = {In vivo imaging of the pathophysiological changes and neutrophil dynamics in influenza virus-infected mouse lungs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6622-E6629}, pmid = {29941581}, issn = {1091-6490}, mesh = {Animals ; Influenza A Virus, H5N1 Subtype/genetics/*metabolism ; *Lung/metabolism/pathology/virology ; Mice ; *Microscopy, Fluorescence, Multiphoton ; Orthomyxoviridae Infections/genetics/*metabolism/*pathology ; }, abstract = {The pathophysiological changes that occur in lungs infected with influenza viruses are poorly understood. Here we established an in vivo imaging system that combines two-photon excitation microscopy and fluorescent influenza viruses of different pathogenicity. This approach allowed us to monitor and correlate several parameters and physiological changes including the spread of infection, pulmonary permeability, pulmonary perfusion speed, number of recruited neutrophils in infected lungs, and neutrophil motion in the lungs of live mice. Several physiological changes were larger and occurred earlier in mice infected with a highly pathogenic H5N1 influenza virus compared with those infected with a mouse-adapted human strain. These findings demonstrate the potential of our in vivo imaging system to provide novel information about the pathophysiological consequences of virus infections.}, } @article {pmid29941580, year = {2018}, author = {Vahidi, S and Ripstein, ZA and Bonomi, M and Yuwen, T and Mabanglo, MF and Juravsky, JB and Rizzolo, K and Velyvis, A and Houry, WA and Vendruscolo, M and Rubinstein, JL and Kay, LE}, title = {Reversible inhibition of the ClpP protease via an N-terminal conformational switch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6447-E6456}, pmid = {29941580}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Bacterial Proteins/*chemistry ; Endopeptidase Clp/*chemistry ; Hydrophobic and Hydrophilic Interactions ; *Molecular Dynamics Simulation ; Protein Domains ; Staphylococcus aureus/*enzymology ; }, abstract = {Protein homeostasis is critically important for cell viability. Key to this process is the refolding of misfolded or aggregated proteins by molecular chaperones or, alternatively, their degradation by proteases. In most prokaryotes and in chloroplasts and mitochondria, protein degradation is performed by the caseinolytic protease ClpP, a tetradecamer barrel-like proteolytic complex. Dysregulating ClpP function has shown promise in fighting antibiotic resistance and as a potential therapy for acute myeloid leukemia. Here we use methyl-transverse relaxation-optimized spectroscopy (TROSY)-based NMR, cryo-EM, biochemical assays, and molecular dynamics simulations to characterize the structural dynamics of ClpP from Staphylococcus aureus (SaClpP) in wild-type and mutant forms in an effort to discover conformational hotspots that regulate its function. Wild-type SaClpP was found exclusively in the active extended form, with the N-terminal domains of its component protomers in predominantly β-hairpin conformations that are less well-defined than other regions of the protein. A hydrophobic site was identified that, upon mutation, leads to unfolding of the N-terminal domains, loss of SaClpP activity, and formation of a previously unobserved split-ring conformation with a pair of 20-Å-wide pores in the side of the complex. The extended form of the structure and partial activity can be restored via binding of ADEP small-molecule activators. The observed structural plasticity of the N-terminal gates is shown to be a conserved feature through studies of Escherichia coli and Neisseria meningitidis ClpP, suggesting a potential avenue for the development of molecules to allosterically modulate the function of ClpP.}, } @article {pmid29941579, year = {2018}, author = {Sherrer, SM and Penland, E and Modrich, P}, title = {The mutagen and carcinogen cadmium is a high-affinity inhibitor of the zinc-dependent MutLα endonuclease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7314-7319}, pmid = {29941579}, issn = {1091-6490}, support = {R01 GM045190/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cadmium/*chemistry ; Carcinogens/*chemistry ; *DNA Mismatch Repair ; Enzyme Inhibitors/*chemistry ; Humans ; MutL Proteins/*chemistry/metabolism ; Mutagens/*chemistry ; *Protein Multimerization ; }, abstract = {MutLα (MLH1-PMS2 heterodimer), which acts as a strand-directed endonuclease during the initiation of eukaryotic mismatch repair, has been postulated to function as a zinc-dependent enzyme [Kosinski J, Plotz G, Guarné A, Bujnicki JM, Friedhoff P (2008) J Mol Biol 382:610-627]. We show that human MutLα copurifies with two bound zinc ions, at least one of which resides within the endonuclease active site, and that bound zinc is required for endonuclease function. Mutagenic action of the carcinogen cadmium, a known inhibitor of zinc-dependent enzymes, is largely due to selective inhibition of mismatch repair [Jin YH, et al. (2003) Nat Genet 34:326-329]. We show that cadmium is a potent inhibitor (apparent Ki ∼ 200 nM) of MutLα endonuclease and that cadmium inhibition is reversed by zinc. We also show that inhibition of mismatch repair in cadmium-treated nuclear extract is significantly reversed by exogenous MutLα but not by MutSα (MSH2-MSH6 heterodimer) and that MutLα reversal depends on integrity of the endonuclease active site. Exogenous MutLα also partially rescues the mismatch repair defect in nuclear extract prepared from cells exposed to cadmium. These findings indicate that targeted inhibition of MutLα endonuclease contributes to cadmium inhibition of mismatch repair. This effect may play a role in the mechanism of cadmium carcinogenesis.}, } @article {pmid29941578, year = {2018}, author = {Honda, T and Nagao, S and Hashimoto, Y and Ishikawa, K and Yokota, T and Mizusawa, H and Ito, M}, title = {Tandem internal models execute motor learning in the cerebellum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7428-7433}, pmid = {29941578}, issn = {1091-6490}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cerebellum/*pathology ; Female ; Hand/physiology ; Humans ; Learning/*physiology ; Male ; Middle Aged ; *Models, Neurological ; Motor Activity/*physiology ; }, abstract = {In performing skillful movement, humans use predictions from internal models formed by repetition learning. However, the computational organization of internal models in the brain remains unknown. Here, we demonstrate that a computational architecture employing a tandem configuration of forward and inverse internal models enables efficient motor learning in the cerebellum. The model predicted learning adaptations observed in hand-reaching experiments in humans wearing a prism lens and explained the kinetic components of these behavioral adaptations. The tandem system also predicted a form of subliminal motor learning that was experimentally validated after training intentional misses of hand targets. Patients with cerebellar degeneration disease showed behavioral impairments consistent with tandemly arranged internal models. These findings validate computational tandemization of internal models in motor control and its potential uses in more complex forms of learning and cognition.}, } @article {pmid29941577, year = {2018}, author = {Nan, Y and Liu, L and Geiser, E and Shu, H and Gong, CC and Dong, Q and Gabrieli, JDE and Desimone, R}, title = {Piano training enhances the neural processing of pitch and improves speech perception in Mandarin-speaking children.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6630-E6639}, pmid = {29941577}, issn = {1091-6490}, mesh = {Attention/*physiology ; Child ; Child, Preschool ; China ; Cognition/*physiology ; Female ; Humans ; *Language ; Male ; Memory, Short-Term/*physiology ; *Music ; Pitch Perception/*physiology ; Speech Perception/*physiology ; }, abstract = {Musical training confers advantages in speech-sound processing, which could play an important role in early childhood education. To understand the mechanisms of this effect, we used event-related potential and behavioral measures in a longitudinal design. Seventy-four Mandarin-speaking children aged 4-5 y old were pseudorandomly assigned to piano training, reading training, or a no-contact control group. Six months of piano training improved behavioral auditory word discrimination in general as well as word discrimination based on vowels compared with the controls. The reading group yielded similar trends. However, the piano group demonstrated unique advantages over the reading and control groups in consonant-based word discrimination and in enhanced positive mismatch responses (pMMRs) to lexical tone and musical pitch changes. The improved word discrimination based on consonants correlated with the enhancements in musical pitch pMMRs among the children in the piano group. In contrast, all three groups improved equally on general cognitive measures, including tests of IQ, working memory, and attention. The results suggest strengthened common sound processing across domains as an important mechanism underlying the benefits of musical training on language processing. In addition, although we failed to find far-transfer effects of musical training to general cognition, the near-transfer effects to speech perception establish the potential for musical training to help children improve their language skills. Piano training was not inferior to reading training on direct tests of language function, and it even seemed superior to reading training in enhancing consonant discrimination.}, } @article {pmid29941576, year = {2018}, author = {Borton, MA and Hoyt, DW and Roux, S and Daly, RA and Welch, SA and Nicora, CD and Purvine, S and Eder, EK and Hanson, AJ and Sheets, JM and Morgan, DM and Wolfe, RA and Sharma, S and Carr, TR and Cole, DR and Mouser, PJ and Lipton, MS and Wilkins, MJ and Wrighton, KC}, title = {Coupled laboratory and field investigations resolve microbial interactions that underpin persistence in hydraulically fractured shales.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6585-E6594}, pmid = {29941576}, issn = {1091-6490}, mesh = {Bacteria/classification/*metabolism ; *Hydraulic Fracking ; Microbial Consortia/*physiology ; Natural Gas/*microbiology ; United States ; }, abstract = {Hydraulic fracturing is one of the industrial processes behind the surging natural gas output in the United States. This technology inadvertently creates an engineered microbial ecosystem thousands of meters below Earth's surface. Here, we used laboratory reactors to perform manipulations of persisting shale microbial communities that are currently not feasible in field scenarios. Metaproteomic and metabolite findings from the laboratory were then corroborated using regression-based modeling performed on metagenomic and metabolite data from more than 40 produced fluids from five hydraulically fractured shale wells. Collectively, our findings show that Halanaerobium, Geotoga, and Methanohalophilus strain abundances predict a significant fraction of nitrogen and carbon metabolites in the field. Our laboratory findings also exposed cryptic predatory, cooperative, and competitive interactions that impact microorganisms across fractured shales. Scaling these results from the laboratory to the field identified mechanisms underpinning biogeochemical reactions, yielding knowledge that can be harnessed to potentially increase energy yields and inform management practices in hydraulically fractured shales.}, } @article {pmid29941575, year = {2018}, author = {}, title = {Correction for Mandal et al., Mapping intracellular mechanics on micropatterned substrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6384}, doi = {10.1073/pnas.1809757115}, pmid = {29941575}, issn = {1091-6490}, } @article {pmid29941574, year = {2018}, author = {}, title = {Correction for Artemenko et al., Chemical and mechanical stimuli act on common signal transduction and cytoskeletal networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6669}, doi = {10.1073/pnas.1809926115}, pmid = {29941574}, issn = {1091-6490}, } @article {pmid29941573, year = {2018}, author = {Sampaio, RN and Piechota, EJ and Troian-Gautier, L and Maurer, AB and Hu, K and Schauer, PA and Blair, AD and Berlinguette, CP and Meyer, GJ}, title = {Kinetics teach that electronic coupling lowers the free-energy change that accompanies electron transfer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7248-7253}, pmid = {29941573}, issn = {1091-6490}, abstract = {Electron-transfer theories predict that an increase in the quantum-mechanical mixing (HDA) of electron donor and acceptor wavefunctions at the instant of electron transfer drives equilibrium constants toward unity. Kinetic and equilibrium studies of four acceptor-bridge-donor (A-B-D) compounds reported herein provide experimental validation of this prediction. The compounds have two redox-active groups that differ only by the orientation of the aromatic bridge: a phenyl-thiophene bridge (p) that supports strong electronic coupling of HDA > 1,000 cm-1; and a xylyl-thiophene bridge (x) that prevents planarization and decreases HDA < 100 cm-1 without a significant change in distance. Pulsed-light excitation allowed kinetic determination of the equilibrium constant, Keq In agreement with theory, Keq(p) were closer to unity compared to Keq(x). A van't Hoff analysis provided clear evidence of an adiabatic electron-transfer pathway for p-series and a nonadiabatic pathway for x-series. Collectively, the data show that the absolute magnitude of the thermodynamic driving force for electron transfers are decreased when adiabatic pathways are operative, a finding that should be taken into account in the design of hybrid materials for solar energy conversion.}, } @article {pmid29941572, year = {2018}, author = {Atir, S and Ferguson, MJ}, title = {How gender determines the way we speak about professionals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7278-7283}, pmid = {29941572}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Middle Aged ; *Sex Characteristics ; *Sexism ; *Social Behavior ; *Speech ; }, abstract = {Gender inequality persists in many professions, particularly in high-status fields, such as science, technology, engineering, and math. We report evidence of a form of gender bias that may contribute to this state: gender influences the way that people speak about professionals. When discussing professionals or their work, it is common to refer to them by surname alone (e.g., "Darwin developed the theory of evolution"). We present evidence that people are more likely to refer to male than female professionals in this way. This gender bias emerges in archival data across domains; students reviewing professors online and pundits discussing politicians on the radio are more likely to use surname when speaking about a man (vs. a woman). Participants' self-reported references also indicate a preference for using surname when speaking about male (vs. female) scientists, authors, and others. Finally, experimental evidence provides convergent evidence: participants writing about a fictional male scientist are more likely to refer to him by surname than participants writing about an otherwise identical female scientist. We find that, on average, people are over twice as likely to refer to male professionals by surname than female professionals. Critically, we identified consequences of this gender bias in speaking about professionals. Researchers referred to by surname are judged as more famous and eminent. They are consequently seen as higher status and more deserving of eminence-related benefits and awards. For instance, scientists referred to by surname were seen as 14% more deserving of a National Science Foundation career award.}, } @article {pmid29941571, year = {2018}, author = {Oki, H and Kawahara, K and Maruno, T and Imai, T and Muroga, Y and Fukakusa, S and Iwashita, T and Kobayashi, Y and Matsuda, S and Kodama, T and Iida, T and Yoshida, T and Ohkubo, T and Nakamura, S}, title = {Interplay of a secreted protein with type IVb pilus for efficient enterotoxigenic Escherichia coli colonization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7422-7427}, pmid = {29941571}, issn = {1091-6490}, mesh = {*Bacterial Adhesion ; Crystallography, X-Ray ; Enterotoxigenic Escherichia coli/*chemistry/genetics/metabolism/pathogenicity ; Escherichia coli K12/chemistry/genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/metabolism ; Fimbriae, Bacterial/*chemistry/genetics/metabolism ; Humans ; Operon ; Protein Domains ; }, abstract = {Initial attachment and subsequent colonization of the intestinal epithelium comprise critical events allowing enteric pathogens to survive and express their pathogenesis. In enterotoxigenic Escherichia coli (ETEC), these are mediated by a long proteinaceous fiber termed type IVb pilus (T4bP). We have reported that the colonization factor antigen/III (CFA/III), an operon-encoded T4bP of ETEC, possesses a minor pilin, CofB, that carries an H-type lectin domain at its tip. Although CofB is critical for pilus assembly by forming a trimeric initiator complex, its importance for bacterial attachment remains undefined. Here, we show that T4bP is not sufficient for bacterial attachment, which also requires a secreted protein CofJ, encoded within the same CFA/III operon. The crystal structure of CofB complexed with a peptide encompassing the binding region of CofJ showed that CofJ interacts with CofB by anchoring its flexible N-terminal extension to be embedded deeply into the expected carbohydrate recognition site of the CofB H-type lectin domain. By combining this structure and physicochemical data in solution, we built a plausible model of the CofJ-CFA/III pilus complex, which suggested that CofJ acts as a molecular bridge by binding both T4bP and the host cell membrane. The Fab fragments of a polyclonal antibody against CofJ significantly inhibited bacterial attachment by preventing the adherence of secreted CofJ proteins. These findings signify the interplay between T4bP and a secreted protein for attaching to and colonizing the host cell surface, potentially constituting a therapeutic target against ETEC infection.}, } @article {pmid29941570, year = {2018}, author = {Böhm, R and Theelen, MMP and Rusch, H and Van Lange, PAM}, title = {Costs, needs, and integration efforts shape helping behavior toward refugees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7284-7289}, pmid = {29941570}, issn = {1091-6490}, mesh = {Adult ; Community Integration/*economics/*psychology ; Costs and Cost Analysis ; *Emigration and Immigration ; Female ; Humans ; Male ; Middle Aged ; Refugees/*psychology ; *Social Behavior ; }, abstract = {Recent political instabilities and conflicts around the world have drastically increased the number of people seeking refuge. The challenges associated with the large number of arriving refugees have revealed a deep divide among the citizens of host countries: one group welcomes refugees, whereas another rejects them. Our research aim is to identify factors that help us understand host citizens' (un)willingness to help refugees. We devise an economic game that captures the basic structural properties of the refugee situation. We use it to investigate both economic and psychological determinants of citizens' prosocial behavior toward refugees. In three controlled laboratory studies, we find that helping refugees becomes less likely when it is individually costly to the citizens. At the same time, helping becomes more likely with the refugees' neediness: helping increases when it prevents a loss rather than generates a gain for the refugees. Moreover, particularly citizens with higher degrees of prosocial orientation are willing to provide help at a personal cost. When refugees have to exert a minimum level of effort to be eligible for support by the citizens, these mandatory "integration efforts" further increase prosocial citizens' willingness to help. Our results underscore that economic factors play a key role in shaping individual refugee helping behavior but also show that psychological factors modulate how individuals respond to them. Moreover, our economic game is a useful complement to correlational survey measures and can be used for pretesting policy measures aimed at promoting prosocial behavior toward refugees.}, } @article {pmid29941569, year = {2018}, author = {Hards, K and McMillan, DGG and Schurig-Briccio, LA and Gennis, RB and Lill, H and Bald, D and Cook, GM}, title = {Ionophoric effects of the antitubercular drug bedaquiline.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7326-7331}, pmid = {29941569}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/*biosynthesis ; Antitubercular Agents/*pharmacology ; Diarylquinolines/*pharmacology ; Escherichia coli/*metabolism ; Escherichia coli Proteins/*metabolism ; Hydrogen-Ion Concentration ; Ionophores/*pharmacology ; Proton-Translocating ATPases/*metabolism ; }, abstract = {Bedaquiline (BDQ), an inhibitor of the mycobacterial F1Fo-ATP synthase, has revolutionized the antitubercular drug discovery program by defining energy metabolism as a potent new target space. Several studies have recently suggested that BDQ ultimately causes mycobacterial cell death through a phenomenon known as uncoupling. The biochemical basis underlying this, in BDQ, is unresolved and may represent a new pathway to the development of effective therapeutics. In this communication, we demonstrate that BDQ can inhibit ATP synthesis in Escherichia coli by functioning as a H+/K+ ionophore, causing transmembrane pH and potassium gradients to be equilibrated. Despite the apparent lack of a BDQ-binding site, incorporating the E. coli Fo subunit into liposomes enhanced the ionophoric activity of BDQ. We discuss the possibility that localization of BDQ at F1Fo-ATP synthases enables BDQ to create an uncoupled microenvironment, by antiporting H+/K+ Ionophoric properties may be desirable in high-affinity antimicrobials targeting integral membrane proteins.}, } @article {pmid29941568, year = {2018}, author = {Monni, R and Capano, G and Auböck, G and Gray, HB and Vlček, A and Tavernelli, I and Chergui, M}, title = {Vibrational coherence transfer in the ultrafast intersystem crossing of a diplatinum complex in solution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6396-E6403}, pmid = {29941568}, issn = {1091-6490}, abstract = {We investigate the ultrafast transient absorption response of tetrakis(μ-pyrophosphito)diplatinate(II), [Pt2(μ-P2O5H2)4]4- [hereafter abbreviated Pt(pop)], in acetonitrile upon excitation of its lowest singlet 1A2u state. Compared with previously reported solvents [van der Veen RM, Cannizzo A, van Mourik F, Vlček A, Jr, Chergui M (2011) J Am Chem Soc 133:305-315], a significant shortening of the intersystem crossing (ISC) time (<1 ps) from the lowest singlet to the lowest triplet state is found, allowing for a transfer of vibrational coherence, observed in the course of an ISC in a polyatomic molecule in solution. Density functional theory (DFT) quantum mechanical/molecular mechanical (QM/MM) simulations of Pt(pop) in acetonitrile and ethanol show that high-lying, mostly triplet, states are strongly mixed and shifted to lower energies due to interactions with the solvent, providing an intermediate state (or manifold of states) for the ISC. This suggests that the larger the solvation energies of the intermediate state(s), the shorter the ISC time. Because the latter is smaller than the pure dephasing time of the vibrational wave packet, coherence is conserved during the spin transition. These results underscore the crucial role of the solvent in directing pathways of intramolecular energy flow.}, } @article {pmid29941567, year = {2018}, author = {White, LA and Forester, JD and Craft, ME}, title = {Disease outbreak thresholds emerge from interactions between movement behavior, landscape structure, and epidemiology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7374-7379}, pmid = {29941567}, issn = {1091-6490}, mesh = {*Animal Migration ; Animals ; Communicable Diseases/*epidemiology ; *Disease Outbreaks ; *Disease Transmission, Infectious ; *Host-Pathogen Interactions ; Humans ; *Models, Biological ; }, abstract = {Disease models have provided conflicting evidence as to whether spatial heterogeneity promotes or impedes pathogen persistence. Moreover, there has been limited theoretical investigation into how animal movement behavior interacts with the spatial organization of resources (e.g., clustered, random, uniform) across a landscape to affect infectious disease dynamics. Importantly, spatial heterogeneity of resources can sometimes lead to nonlinear or counterintuitive outcomes depending on the host and pathogen system. There is a clear need to develop a general theoretical framework that could be used to create testable predictions for specific host-pathogen systems. Here, we develop an individual-based model integrated with movement ecology approaches to investigate how host movement behaviors interact with landscape heterogeneity (in the form of various levels of resource abundance and clustering) to affect pathogen dynamics. For most of the parameter space, our results support the counterintuitive idea that fragmentation promotes pathogen persistence, but this finding was largely dependent on perceptual range of the host, conspecific density, and recovery rate. For simulations with high conspecific density, slower recovery rates, and larger perceptual ranges, more complex disease dynamics emerged, and the most fragmented landscapes were not necessarily the most conducive to outbreaks or pathogen persistence. These results point to the importance of interactions between landscape structure, individual movement behavior, and pathogen transmission for predicting and understanding disease dynamics.}, } @article {pmid29941566, year = {2018}, author = {}, title = {Correction for Fustin et al., Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6386}, doi = {10.1073/pnas.1809838115}, pmid = {29941566}, issn = {1091-6490}, } @article {pmid29941565, year = {2018}, author = {Bhattacharya, M and Berends, ETM and Chan, R and Schwab, E and Roy, S and Sen, CK and Torres, VJ and Wozniak, DJ}, title = {Staphylococcus aureus biofilms release leukocidins to elicit extracellular trap formation and evade neutrophil-mediated killing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7416-7421}, pmid = {29941565}, issn = {1091-6490}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; R01 AI099394/AI/NIAID NIH HHS/United States ; R01 AI105129/AI/NIAID NIH HHS/United States ; R01 NR013898/NR/NINR NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/*immunology ; *Biofilms ; Extracellular Traps/*immunology/microbiology ; Humans ; *Immune Evasion ; Leukocidins/*immunology ; Neutrophils/*immunology ; Staphylococcal Skin Infections/*immunology/pathology ; Staphylococcus aureus/*physiology ; Swine ; Wound Infection/*immunology/microbiology/pathology ; }, abstract = {Bacterial biofilms efficiently evade immune defenses, greatly complicating the prognosis of chronic infections. How methicillin-resistant Staphylococcus aureus (MRSA) biofilms evade host immune defenses is largely unknown. This study describes some of the major mechanisms required for S. aureus biofilms to evade the innate immune response and provides evidence of key virulence factors required for survival and persistence of bacteria during chronic infections. Neutrophils are the most abundant white blood cells in circulation, playing crucial roles in the control and elimination of bacterial pathogens. Specifically, here we show that, unlike single-celled populations, S. aureus biofilms rapidly skew neutrophils toward neutrophil extracellular trap (NET) formation through the combined activity of leukocidins Panton-Valentine leukocidin and γ-hemolysin AB. By eliciting this response, S. aureus was able to persist, as the antimicrobial activity of released NETs was ineffective at clearing biofilm bacteria. Indeed, these studies suggest that NETs could inadvertently potentiate biofilm infections. Last, chronic infection in a porcine burn wound model clearly demonstrated that leukocidins are required for "NETosis" and facilitate bacterial survival in vivo.}, } @article {pmid29941564, year = {2018}, author = {Burdyga, A and Surdo, NC and Monterisi, S and Di Benedetto, G and Grisan, F and Penna, E and Pellegrini, L and Zaccolo, M and Bortolozzi, M and Swietach, P and Pozzan, T and Lefkimmiatis, K}, title = {Phosphatases control PKA-dependent functional microdomains at the outer mitochondrial membrane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6497-E6506}, pmid = {29941564}, issn = {1091-6490}, support = {201603PJT-365052//CIHR/Canada ; RE/13/1/30181//British Heart Foundation/United Kingdom ; RG/12/3/29423//British Heart Foundation/United Kingdom ; PG/15/5/31110//British Heart Foundation/United Kingdom ; }, mesh = {Animals ; Cyclic AMP-Dependent Protein Kinases/genetics/*metabolism ; Fluorescence Resonance Energy Transfer ; HeLa Cells ; Humans ; Membrane Microdomains/*enzymology/genetics ; Membrane Proteins/genetics/*metabolism ; Mitochondrial Membranes/*enzymology ; Mitochondrial Proteins/genetics/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Evidence supporting the heterogeneity in cAMP and PKA signaling is rapidly accumulating and has been largely attributed to the localization or activity of adenylate cyclases, phosphodiesterases, and A-kinase-anchoring proteins in different cellular subcompartments. However, little attention has been paid to the possibility that, despite homogeneous cAMP levels, a major heterogeneity in cAMP/PKA signaling could be generated by the spatial distribution of the final terminators of this cascade, i.e., the phosphatases. Using FRET-based sensors to monitor cAMP and PKA-dependent phosphorylation in the cytosol and outer mitochondrial membrane (OMM) of primary rat cardiomyocytes, we demonstrate that comparable cAMP increases in these two compartments evoke higher levels of PKA-dependent phosphorylation in the OMM. This difference is most evident for small, physiological increases of cAMP levels and with both OMM-located probes and endogenous OMM proteins. We demonstrate that this disparity depends on differences in the rates of phosphatase-dependent dephosphorylation of PKA targets in the two compartments. Furthermore, we show that the activity of soluble phosphatases attenuates PKA-driven activation of the cAMP response element-binding protein while concurrently enhancing PKA-dependent mitochondrial elongation. We conclude that phosphatases can sculpt functionally distinct cAMP/PKA domains even in the absence of gradients or microdomains of this messenger. We present a model that accounts for these unexpected results in which the degree of PKA-dependent phosphorylation is dictated by both the subcellular distribution of the phosphatases and the different accessibility of membrane-bound and soluble phosphorylated substrates to the cytosolic enzymes.}, } @article {pmid29941563, year = {2018}, author = {Glatzmaier, GA}, title = {Computer simulations of Jupiter's deep internal dynamics help interpret what Juno sees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6896-6904}, pmid = {29941563}, issn = {1091-6490}, abstract = {We describe computer simulations of thermal convection and magnetic field generation in Jupiter's deep interior: that is, its convective dynamo. Results from three different simulations highlight the importance of including the dynamics in the very deep interior, although much of the convection and field generation seems to be confined to the upper part of the interior. A long-debated question is to what depth do Jupiter's zonal winds extend below its surface. Our simulations suggest that, if global latitudinally banded patterns in Jupiter's near-surface magnetic and gravity fields were detected by Juno, NASA's orbiting spacecraft at Jupiter [Bolton S, et al. (2017) Science 356:821-825], they would provide evidence for Jupiter's zonal winds extending deep below the surface. One of our simulations has also maintained, for a couple simulated years, a deep axisymmetric inertial wave, with properties at the surface that depend on the size of the model's small rocky core. If such a wave was detected on Jupiter's surface, its latitudes and oscillation frequency would provide evidence for the existence and size of Jupiter's rocky core.}, } @article {pmid29941562, year = {2018}, author = {Værøy, H and Adori, C and Legrand, R and Lucas, N and Breton, J and Cottard, C and do Rego, JC and Duparc, C and Louiset, E and Lefebvre, H and Déchelotte, P and Western, E and Andersson, S and Hökfelt, T and Fetissov, SO}, title = {Autoantibodies reactive to adrenocorticotropic hormone can alter cortisol secretion in both aggressive and nonaggressive humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6576-E6584}, pmid = {29941562}, issn = {1091-6490}, mesh = {*Adrenocorticotropic Hormone/blood/immunology ; Adult ; *Aggression ; *Autoantibodies/blood/immunology ; Humans ; *Hydrocortisone/immunology/metabolism ; *Immunoglobulin G/blood/immunology ; Male ; Norway ; *Stress, Psychological/blood/immunology ; }, abstract = {Violent aggression in humans may involve a modified response to stress, but the underlying mechanisms are not well understood. Here we show that naturally present autoantibodies reactive to adrenocorticotropic hormone (ACTH) exhibit distinct epitope-binding profiles to ACTH peptide in subjects with a history of violent aggression compared with controls. Namely, while nonaggressive male controls displayed a preferential IgG binding to the ACTH central part (amino acids 11-24), subjects who had committed violent acts of aggression had IgG with increased affinity to ACTH, preferentially binding to its N terminus (amino acids 1-13). Purified IgGs from approximately half of the examined sera were able to block ACTH-induced cortisol secretion of human adrenal cells in vitro, irrespective of the source of sample (from a control subject or a violent aggressor). Nevertheless, in the resident-intruder test in mice, i.p. injection of residents with ACTH and IgG from aggressive subjects, but not from control subjects, shortened latency for the first attack against intruders. Immunohistochemical screening of violent aggressors' sera on rat brain and pituitary sections did not show IgG binding to ACTH-producing cells, but 4 of 16 sera revealed selective binding to a nonidentified antigen in vasopressinergic neurons of the hypothalamic paraventricular and supraoptic nuclei. Thus, the data show that ACTH-reactive plasmatic IgGs exhibit differential epitope preference in control and violently aggressive subjects. These IgGs can modulate ACTH-induced cortisol secretion and, hence, are involved in the regulation of the stress response. However, the possible role of ACTH-reactive autoantibodies in aggressive behavior needs further investigation.}, } @article {pmid29941561, year = {2018}, author = {}, title = {Correction to Supporting Information for Smith et al., Direct measurements of meltwater runoff on the Greenland ice sheet surface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6097}, doi = {10.1073/pnas.1809300115}, pmid = {29941561}, issn = {1091-6490}, } @article {pmid29941560, year = {2018}, author = {Klimtchuk, ES and Prokaeva, T and Frame, NM and Abdullahi, HA and Spencer, B and Dasari, S and Cui, H and Berk, JL and Kurtin, PJ and Connors, LH and Gursky, O}, title = {Unusual duplication mutation in a surface loop of human transthyretin leads to an aggressive drug-resistant amyloid disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6428-E6436}, pmid = {29941560}, issn = {1091-6490}, support = {R01 AG031804/AG/NIA NIH HHS/United States ; R01 GM067260/GM/NIGMS NIH HHS/United States ; R56 AG031804/AG/NIA NIH HHS/United States ; T32 HL007969/HL/NHLBI NIH HHS/United States ; }, mesh = {*Amyloid/chemistry/genetics/metabolism ; *Amyloid Neuropathies, Familial/drug therapy/genetics/metabolism ; Diflunisal/*therapeutic use ; *Drug Resistance ; Female ; Humans ; Male ; *Models, Molecular ; Mutation ; *Prealbumin/chemistry/genetics/metabolism ; Protein Structure, Secondary ; }, abstract = {Transthyretin (TTR) is a globular tetrameric transport protein in plasma. Nearly 140 single amino acid substitutions in TTR cause life-threatening amyloid disease. We report a one-of-a-kind pathological variant featuring a Glu51, Ser52 duplication mutation (Glu51_Ser52dup). The proband, heterozygous for the mutation, exhibited an unusually aggressive amyloidosis that was refractory to treatment with the small-molecule drug diflunisal. To understand the poor treatment response and expand therapeutic options, we explored the structure and stability of recombinant Glu51_Ser52dup. The duplication did not alter the protein secondary or tertiary structure but decreased the stability of the TTR monomer and tetramer. Diflunisal, which bound with near-micromolar affinity, partially restored tetramer stability. The duplication had no significant effect on the free energy and enthalpy of diflunisal binding, and hence on the drug-protein interactions. However, the duplication induced tryptic digestion of TTR at near-physiological conditions, releasing a C-terminal fragment 49-129 that formed amyloid fibrils under conditions in which the full-length protein did not. Such C-terminal fragments, along with the full-length TTR, comprise amyloid deposits in vivo. Bioinformatics and structural analyses suggested that increased disorder in the surface loop, which contains the Glu51_Ser52dup duplication, not only helped generate amyloid-forming fragments but also decreased structural protection in the amyloidogenic residue segment 25-34, promoting misfolding of the full-length protein. Our studies of a unique duplication mutation explain its diflunisal-resistant nature, identify misfolding pathways for amyloidogenic TTR variants, and provide therapeutic targets to inhibit amyloid fibril formation by variant TTR.}, } @article {pmid29941559, year = {2018}, author = {Wang, X and Wang, Y and Dou, Y and Chen, L and Wang, J and Jiang, N and Guo, C and Yao, Q and Wang, C and Liu, L and Yu, B and Zheng, B and Chekanova, JA and Ma, J and Ren, G}, title = {Degradation of unmethylated miRNA/miRNA*s by a DEDDy-type 3' to 5' exoribonuclease Atrimmer 2 in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6659-E6667}, pmid = {29941559}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Exoribonucleases/genetics/*metabolism ; Methylation ; MicroRNAs/genetics/*metabolism ; *Mutation ; RNA, Plant/genetics/*metabolism ; }, abstract = {The 3' end methylation catalyzed by HUA Enhancer 1 (HEN1) is a crucial step of small RNA stabilization in plants, yet how unmethylated small RNAs undergo degradation remains largely unknown. Using a reverse genetic approach, we here show that Atrimmer 2 (ATRM2), a DEDDy-type 3' to 5' exoribonuclease, acts in the degradation of unmethylated miRNAs and miRNA*s in Arabidopsis Loss-of-function mutations in ATRM2 partially suppress the morphological defects caused by HEN1 malfunction, with restored levels of a subset of miRNAs and receded expression of corresponding miRNA targets. Dysfunction of ATRM2 has negligible effect on miRNA trimming, and further increase the fertility of hen1 heso1 urt1, a mutant with an almost complete abolishment of miRNA uridylation, indicating that ATRM2 may neither be involved in 3' to 5' trimming nor be the enzyme that specifically degrades uridylated miRNAs. Notably, the fold changes of miRNAs and their corresponding miRNA*s were significantly correlated in hen1 atrm2 versus hen1 Unexpectedly, we observed a marked increase of 3' to 5' trimming of several miRNA*s but not miRNAs in ATRM2 compromised backgrounds. These data suggest an action of ATRM2 on miRNA/miRNA* duplexes, and the existence of an unknown exoribonuclease for specific trimming of miRNA*. This asymmetric effect on miRNA/miRNA* is likely related to Argonaute (AGO) proteins, which can distinguish miRNAs from miRNA*s. Finally, we show that ATRM2 colocalizes and physically interacts with Argonaute 1 (AGO1). Taken together, our results suggest that ATRM2 may be involved in the surveillance of unmethylated miRNA/miRNA* duplexes during the initiation step of RNA-induced silencing complex assembly.}, } @article {pmid29941558, year = {2018}, author = {Yang, XG and Zhang, G and Ge, S and Wang, CY}, title = {Fast charging of lithium-ion batteries at all temperatures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7266-7271}, pmid = {29941558}, issn = {1091-6490}, abstract = {Fast charging is a key enabler of mainstream adoption of electric vehicles (EVs). None of today's EVs can withstand fast charging in cold or even cool temperatures due to the risk of lithium plating. Efforts to enable fast charging are hampered by the trade-off nature of a lithium-ion battery: Improving low-temperature fast charging capability usually comes with sacrificing cell durability. Here, we present a controllable cell structure to break this trade-off and enable lithium plating-free (LPF) fast charging. Further, the LPF cell gives rise to a unified charging practice independent of ambient temperature, offering a platform for the development of battery materials without temperature restrictions. We demonstrate a 9.5 Ah 170 Wh/kg LPF cell that can be charged to 80% state of charge in 15 min even at -50 °C (beyond cell operation limit). Further, the LPF cell sustains 4,500 cycles of 3.5-C charging in 0 °C with <20% capacity loss, which is a 90× boost of life compared with a baseline conventional cell, and equivalent to >12 y and >280,000 miles of EV lifetime under this extreme usage condition, i.e., 3.5-C or 15-min fast charging at freezing temperatures.}, } @article {pmid29941557, year = {2018}, author = {Ramadi, KB and Dagdeviren, C and Spencer, KC and Joe, P and Cotler, M and Rousseau, E and Nunez-Lopez, C and Graybiel, AM and Langer, R and Cima, MJ}, title = {Focal, remote-controlled, chronic chemical modulation of brain microstructures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7254-7259}, pmid = {29941557}, issn = {1091-6490}, support = {P30 CA014051/CA/NCI NIH HHS/United States ; R01 EB016101/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Basal Ganglia/*diagnostic imaging ; Copper/*pharmacology ; *Drug Delivery Systems/instrumentation/methods ; Fluorodeoxyglucose F18/*pharmacology ; Magnetic Resonance Imaging/*methods ; Rats ; Substantia Nigra/*diagnostic imaging ; }, abstract = {Direct delivery of fluid to brain parenchyma is critical in both research and clinical settings. This is usually accomplished through acutely inserted cannulas. This technique, however, results in backflow and significant dispersion away from the infusion site, offering little spatial or temporal control in delivering fluid. We present an implantable, MRI-compatible, remotely controlled drug delivery system for minimally invasive interfacing with brain microstructures in freely moving animals. We show that infusions through acutely inserted needles target a region more than twofold larger than that of identical infusions through chronically implanted probes due to reflux and backflow. We characterize the dynamics of in vivo infusions using positron emission tomography techniques. Volumes as small as 167 nL of copper-64 and fludeoxyglucose labeled agents are quantified. We further demonstrate the importance of precise drug volume dosing to neural structures to elicit behavioral effects reliably. Selective modulation of the substantia nigra, a critical node in basal ganglia circuitry, via muscimol infusion induces behavioral changes in a volume-dependent manner, even when the total dose remains constant. Chronic device viability is confirmed up to 1-y implantation in rats. This technology could potentially enable precise investigation of neurological disease pathology in preclinical models, and more efficacious treatment in human patients.}, } @article {pmid29941556, year = {2018}, author = {Brusini, I and Carneiro, M and Wang, C and Rubin, CJ and Ring, H and Afonso, S and Blanco-Aguiar, JA and Ferrand, N and Rafati, N and Villafuerte, R and Smedby, Ö and Damberg, P and Hallböök, F and Fredrikson, M and Andersson, L}, title = {Changes in brain architecture are consistent with altered fear processing in domestic rabbits.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7380-7385}, pmid = {29941556}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; *Domestication ; Fear/*physiology ; *Gray Matter/anatomy & histology/physiology ; *Prefrontal Cortex/anatomy & histology/physiology ; Rabbits ; *White Matter/anatomy & histology/physiology ; }, abstract = {The most characteristic feature of domestic animals is their change in behavior associated with selection for tameness. Here we show, using high-resolution brain magnetic resonance imaging in wild and domestic rabbits, that domestication reduced amygdala volume and enlarged medial prefrontal cortex volume, supporting that areas driving fear have lost volume while areas modulating negative affect have gained volume during domestication. In contrast to the localized gray matter alterations, white matter anisotropy was reduced in the corona radiata, corpus callosum, and the subcortical white matter. This suggests a compromised white matter structural integrity in projection and association fibers affecting both afferent and efferent neural flow, consistent with reduced neural processing. We propose that compared with their wild ancestors, domestic rabbits are less fearful and have an attenuated flight response because of these changes in brain architecture.}, } @article {pmid29941555, year = {2018}, author = {Pieraccioli, M and Nicolai, S and Pitolli, C and Agostini, M and Antonov, A and Malewicz, M and Knight, RA and Raschellà, G and Melino, G}, title = {ZNF281 inhibits neuronal differentiation and is a prognostic marker for neuroblastoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7356-7361}, pmid = {29941555}, issn = {1091-6490}, support = {//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Biomarkers, Tumor/*biosynthesis/genetics ; *Cell Differentiation ; Cell Line, Tumor ; Gene Expression Regulation, Neoplastic ; Humans ; Mice ; Neoplasm Proteins/*biosynthesis/genetics ; Neuroblastoma/diagnosis/genetics/*metabolism/pathology ; Neurons/*metabolism/pathology ; Prognosis ; Trans-Activators/*biosynthesis/genetics ; Transcription Factors/*biosynthesis/genetics ; }, abstract = {Derangement of cellular differentiation because of mutation or inappropriate expression of specific genes is a common feature in tumors. Here, we show that the expression of ZNF281, a zinc finger factor involved in several cellular processes, decreases during terminal differentiation of murine cortical neurons and in retinoic acid-induced differentiation of neuroblastoma (NB) cells. The ectopic expression of ZNF281 inhibits the neuronal differentiation of murine cortical neurons and NB cells, whereas its silencing causes the opposite effect. Furthermore, TAp73 inhibits the expression of ZNF281 through miR34a. Conversely, MYCN promotes the expression of ZNF281 at least in part by inhibiting miR34a. These findings imply a functional network that includes p73, MYCN, and ZNF281 in NB cells, where ZNF281 acts by negatively affecting neuronal differentiation. Array analysis of NB cells silenced for ZNF281 expression identified GDNF and NRP2 as two transcriptional targets inhibited by ZNF281. Binding of ZNF281 to the promoters of these genes suggests a direct mechanism of repression. Bioinformatic analysis of NB datasets indicates that ZNF281 expression is higher in aggressive, undifferentiated stage 4 than in localized stage 1 tumors supporting a central role of ZNF281 in affecting the differentiation of NB. Furthermore, patients with NB with high expression of ZNF281 have a poor clinical outcome compared with low-expressors. These observations suggest that ZNF281 is a controller of neuronal differentiation that should be evaluated as a prognostic marker in NB.}, } @article {pmid29941554, year = {2018}, author = {Jiahui, G and Yang, H and Duchaine, B}, title = {Developmental prosopagnosics have widespread selectivity reductions across category-selective visual cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6418-E6427}, pmid = {29941554}, issn = {1091-6490}, mesh = {*Facial Recognition ; Female ; Humans ; Male ; Prosopagnosia/*physiopathology ; Visual Cortex/*physiopathology ; }, abstract = {Developmental prosopagnosia (DP) is a neurodevelopmental disorder characterized by severe deficits with facial identity recognition. It is unclear which cortical areas contribute to face processing deficits in DP, and no previous studies have investigated whether other category-selective areas function normally in DP. To address these issues, we scanned 22 DPs and 27 controls using a dynamic localizer consisting of video clips of faces, scenes, bodies, objects, and scrambled objects. We then analyzed category selectivity, a measure of the tuning of a cortical area to a particular visual category. DPs exhibited reduced face selectivity in all 12 face areas, and the reductions were significant in three posterior and two anterior areas. DPs and controls showed similar responses to faces in other category-selective areas, which suggests the DPs' behavioral deficits with faces result from problems restricted to the face network. DPs also had pronounced scene-selectivity reductions in four of six scene-selective areas and marginal body-selectivity reductions in two of four body-selective areas. Our results demonstrate that DPs have widespread deficits throughout the face network, and they are inconsistent with a leading account of DP which proposes that posterior face-selective areas are normal in DP. The selectivity reductions in other category-selective areas indicate many DPs have deficits spread across high-level visual cortex.}, } @article {pmid29941553, year = {2018}, author = {Banerjee, A and Ibsen, K and Brown, T and Chen, R and Agatemor, C and Mitragotri, S}, title = {Ionic liquids for oral insulin delivery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7296-7301}, pmid = {29941553}, issn = {1091-6490}, support = {R01 DK097379/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Blood Glucose/*metabolism ; Capsules ; Choline/pharmacokinetics/pharmacology ; Dose-Response Relationship, Drug ; Humans ; *Insulin/pharmacokinetics/pharmacology ; *Ionic Liquids/pharmacokinetics/pharmacology ; Male ; Rats ; Rats, Wistar ; Terpenes/pharmacokinetics/pharmacology ; }, abstract = {With the rise in diabetes mellitus cases worldwide and lack of patient adherence to glycemia management using injectable insulin, there is an urgent need for the development of efficient oral insulin formulations. However, the gastrointestinal tract presents a formidable barrier to oral delivery of biologics. Here we report the development of a highly effective oral insulin formulation using choline and geranate (CAGE) ionic liquid. CAGE significantly enhanced paracellular transport of insulin, while protecting it from enzymatic degradation and by interacting with the mucus layer resulting in its thinning. In vivo, insulin-CAGE demonstrated exceptional pharmacokinetic and pharmacodynamic outcome after jejunal administration in rats. Low insulin doses (3-10 U/kg) brought about a significant decrease in blood glucose levels, which were sustained for longer periods (up to 12 hours), unlike s.c. injected insulin. When 10 U/kg insulin-CAGE was orally delivered in enterically coated capsules using an oral gavage, a sustained decrease in blood glucose of up to 45% was observed. The formulation exhibited high biocompatibility and was stable for 2 months at room temperature and for at least 4 months under refrigeration. Taken together, the results indicate that CAGE is a promising oral delivery vehicle and should be further explored for oral delivery of insulin and other biologics that are currently marketed as injectables.}, } @article {pmid29941552, year = {2018}, author = {Walters, WA and Jin, Z and Youngblut, N and Wallace, JG and Sutter, J and Zhang, W and González-Peña, A and Peiffer, J and Koren, O and Shi, Q and Knight, R and Glavina Del Rio, T and Tringe, SG and Buckler, ES and Dangl, JL and Ley, RE}, title = {Large-scale replicated field study of maize rhizosphere identifies heritable microbes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7368-7373}, pmid = {29941552}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Genotype ; *Inbreeding ; Microbiota/*physiology ; Plant Roots/*microbiology ; *Rhizosphere ; Zea mays/genetics/*microbiology ; }, abstract = {Soil microbes that colonize plant roots and are responsive to differences in plant genotype remain to be ascertained for agronomically important crops. From a very large-scale longitudinal field study of 27 maize inbred lines planted in three fields, with partial replication 5 y later, we identify root-associated microbiota exhibiting reproducible associations with plant genotype. Analysis of 4,866 samples identified 143 operational taxonomic units (OTUs) whose variation in relative abundances across the samples was significantly regulated by plant genotype, and included five of seven core OTUs present in all samples. Plant genetic effects were significant amid the large effects of plant age on the rhizosphere microbiome, regardless of the specific community of each field, and despite microbiome responses to climate events. Seasonal patterns showed that the plant root microbiome is locally seeded, changes with plant growth, and responds to weather events. However, against this background of variation, specific taxa responded to differences in host genotype. If shown to have beneficial functions, microbes may be considered candidate traits for selective breeding.}, } @article {pmid29941551, year = {2018}, author = {Guo, S and Samanta, D and Peng, Y and Xu, X and Cheng, X}, title = {Symmetric shear banding and swarming vortices in bacterial superfluids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7212-7217}, pmid = {29941551}, issn = {1091-6490}, mesh = {Escherichia coli K12/*cytology/*physiology ; *Models, Biological ; *Shear Strength ; }, abstract = {Bacterial suspensions-a premier example of active fluids-show an unusual response to shear stresses. Instead of increasing the viscosity of the suspending fluid, the emergent collective motions of swimming bacteria can turn a suspension into a superfluid with zero apparent viscosity. Although the existence of active superfluids has been demonstrated in bulk rheological measurements, the microscopic origin and dynamics of such an exotic phase have not been experimentally probed. Here, using high-speed confocal rheometry, we study the dynamics of concentrated bacterial suspensions under simple planar shear. We find that bacterial superfluids under shear exhibit unusual symmetric shear bands, defying the conventional wisdom on shear banding of complex fluids, where the formation of steady shear bands necessarily breaks the symmetry of unsheared samples. We propose a simple hydrodynamic model based on the local stress balance and the ergodic sampling of nonequilibrium shear configurations, which quantitatively describes the observed symmetric shear-banding structure. The model also successfully predicts various interesting features of swarming vortices in stationary bacterial suspensions. Our study provides insights into the physical properties of collective swarming in active fluids and illustrates their profound influences on transport processes.}, } @article {pmid29941550, year = {2018}, author = {Wei, H and Vejerano, EP and Leng, W and Huang, Q and Willner, MR and Marr, LC and Vikesland, PJ}, title = {Aerosol microdroplets exhibit a stable pH gradient.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7272-7277}, pmid = {29941550}, issn = {1091-6490}, support = {DP2 AI112243/AI/NIAID NIH HHS/United States ; }, mesh = {Aerosols ; Benzoates/*chemistry ; Catalysis ; Gold/*chemistry ; Hydrogen-Ion Concentration ; Metal Nanoparticles/*chemistry ; Sulfhydryl Compounds/*chemistry ; }, abstract = {Suspended aqueous aerosol droplets (<50 µm) are microreactors for many important atmospheric reactions. In droplets and other aquatic environments, pH is arguably the key parameter dictating chemical and biological processes. The nature of the droplet air/water interface has the potential to significantly alter droplet pH relative to bulk water. Historically, it has been challenging to measure the pH of individual droplets because of their inaccessibility to conventional pH probes. In this study, we scanned droplets containing 4-mercaptobenzoic acid-functionalized gold nanoparticle pH nanoprobes by 2D and 3D laser confocal Raman microscopy. Using surface-enhanced Raman scattering, we acquired the pH distribution inside approximately 20-µm-diameter phosphate-buffered aerosol droplets and found that the pH in the core of a droplet is higher than that of bulk solution by up to 3.6 pH units. This finding suggests the accumulation of protons at the air/water interface and is consistent with recent thermodynamic model results. The existence of this pH shift was corroborated by the observation that a catalytic reaction that occurs only under basic conditions (i.e., dimerization of 4-aminothiophenol to produce dimercaptoazobenzene) occurs within the high pH core of a droplet, but not in bulk solution. Our nanoparticle probe enables pH quantification through the cross-section of an aerosol droplet, revealing a spatial gradient that has implications for acid-base-catalyzed atmospheric chemistry.}, } @article {pmid29941292, year = {2018}, author = {van Dijk, EL and Jaszczyszyn, Y and Naquin, D and Thermes, C}, title = {The Third Revolution in Sequencing Technology.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {9}, pages = {666-681}, doi = {10.1016/j.tig.2018.05.008}, pmid = {29941292}, issn = {0168-9525}, abstract = {Forty years ago the advent of Sanger sequencing was revolutionary as it allowed complete genome sequences to be deciphered for the first time. A second revolution came when next-generation sequencing (NGS) technologies appeared, which made genome sequencing much cheaper and faster. However, NGS methods have several drawbacks and pitfalls, most notably their short reads. Recently, third-generation/long-read methods appeared, which can produce genome assemblies of unprecedented quality. Moreover, these technologies can directly detect epigenetic modifications on native DNA and allow whole-transcript sequencing without the need for assembly. This marks the third revolution in sequencing technology. Here we review and compare the various long-read methods. We discuss their applications and their respective strengths and weaknesses and provide future perspectives.}, } @article {pmid29941205, year = {2018}, author = {Cortés, A and Toledo, R and Cantacessi, C}, title = {Classic Models for New Perspectives: Delving into Helminth-Microbiota-Immune System Interactions.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {640-654}, doi = {10.1016/j.pt.2018.05.009}, pmid = {29941205}, issn = {1471-5007}, mesh = {Animals ; *Helminthiasis/immunology/microbiology ; Host-Parasite Interactions/*immunology ; Humans ; *Models, Biological ; }, abstract = {Whilst a wealth of data indicate that infections by gastrointestinal helminths are accompanied by significant alterations in the composition of the vertebrate gut flora, little is known of the immune-molecular mechanisms that regulate host-parasite-microbiota interactions. 'Traditional' experimental models of gastrointestinal helminthiases, in which the role(s) of each of the components of this triad can be tested, provide an opportunity to advance research in this area. In this article, we propose the Echinostoma caproni-mouse system as a potentially useful tool for studies of the role of the host gut microbiota in preventing pathology and inducing parasite clearance via interleukin (IL)-25, an epithelial-derived alarmin with key roles in antihelminth immunity and maintenance of gut homeostasis.}, } @article {pmid29941188, year = {2018}, author = {Lowe-Power, TM and Khokhani, D and Allen, C}, title = {How Ralstonia solanacearum Exploits and Thrives in the Flowing Plant Xylem Environment.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {929-942}, doi = {10.1016/j.tim.2018.06.002}, pmid = {29941188}, issn = {1878-4380}, abstract = {The plant wilt pathogen Ralstonia solanacearum thrives in the water-transporting xylem vessels of its host plants. Xylem is a relatively nutrient-poor, high-flow environment but R. solanacearum succeeds there by tuning its own metabolism and altering xylem sap biochemistry. Flow influences many traits that the bacterium requires for pathogenesis. Most notably, a quorum sensing system mediates the pathogen's major transition from a rapidly dividing early phase that voraciously consumes diverse food sources and avidly adheres to plant surfaces to a slower-growing late phase that can use fewer nutrients but produces virulence factors and disperses effectively. This review discusses recent findings about R. solanacearum pathogenesis in the context of its flowing in planta niche, with emphasis on R. solanacearum metabolism in plants.}, } @article {pmid29941048, year = {2018}, author = {Plotkin, BJ and Sigar, IM and Swartzendruber, JA and Kaminski, A and Davis, J}, title = {Differential expression of cytokines and receptor expression during anoxic growth.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {406}, pmid = {29941048}, issn = {1756-0500}, mesh = {*Cell Hypoxia ; Cytokines/*metabolism ; *Gene Expression ; HeLa Cells ; Humans ; Neoplasms/drug therapy/physiopathology ; Oxygen ; }, abstract = {OBJECTIVE: Cell density in tumor cell three dimensional (3D) cultures affects secretome expression of components. A microenvironment characteristic shared by high-density 3D cell culture and in vivo tumor masses is poor oxygenation, with anoxia being a natural cell state in tumor centers. Until recently, the ability to study anoxia-adapted cell physiology was not possible. Using a newly-developed methodology, anoxic HeLa cell secretome expression was measured.

RESULTS: Anoxic HeLa cell cytokine levels after 3 days' (hypoxia inducible factor, HIF1 positive) and 10 days' growth (HIF1 negative; anaerobic respiration) were significantly (p < 0.01) higher than normoxic controls for: IL-8 (1.8- and 3.4-fold higher, respectively), GRO (1.3- and 1.1-fold higher, respectively), and IL-11 (1.4- and 1.1-fold higher, respectively). In contrast, G-CSF, IFNα2, and CXCL-10 levels decreased over time (day 3 vs. day 10). Thus, metabolically active HeLa cells respond to the lack of oxygen, in part, by regulating the levels of cytokines produced. Cytokines expressed at increased levels, in the absence of oxygen, correspond to a secretomic profile reported for paracrine signaling pathways associated with metastasis. Further studies defining physiologic changes that occur upon anoxic growth may lead to the discovery of novel chemotherapeutic drug targets.}, } @article {pmid29941046, year = {2018}, author = {Migriauli, I and Meunargia, V and Chkhaidze, I and Sabakhtarishvili, G and Gujabidze, K and Butsashvili, M and Kamkamidze, G}, title = {Factors affecting development of Clostridium difficile infection in hospitalized pediatric patients in the country Georgia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {409}, pmid = {29941046}, issn = {1756-0500}, support = {grant # PhDF2016_69//Shota Rustaveli National Science Foundation/ ; }, mesh = {Adolescent ; Child ; Child, Preschool ; *Clostridium Infections/drug therapy/epidemiology/etiology ; Clostridium difficile/*isolation & purification ; *Cross Infection ; Cross-Sectional Studies ; Diarrhea ; Feces ; Female ; Georgia (Republic) ; Humans ; Male ; Spain ; }, abstract = {OBJECTIVE: Main aims of our study were to investigate occurrence of Clostridium difficile among hospitalized pediatric patients in Georgia and examine risk factors for the development of C. difficile infection. During our study we tested and piloted the real-time PCR diagnostic systems for rapid and simultaneous identification of C. difficile and number of other pathogens in our facility settings. A cross-sectional study has been performed in children less than 18 years of age in two pediatric hospitals in Georgia, between May 2016 and December 2017. Stool specimens negative by the conventional bacteriology analysis were analyzed for the presence of C. difficile and several viral and protozoa pathogens using enzyme immune assay and polymerase chain reaction. In total samples from 220 hospitalized children with gastroenteritis symptoms were analyzed in this study.

RESULTS: The average age of the study participants was 4.7 years. Overall 23 children were identified positive for C. difficile (10.5%). Antibiotic exposure within 2 months preceding the onset of diarrhea was associated with an increased risk of C. difficile infections. The risk was greatest with cephalosporins, followed by penicillins, carbapenems and macrolides. Clostridium difficile is an important cause of healthcare-associated diarrhea in pediatric population of Georgia.}, } @article {pmid29941023, year = {2018}, author = {Wemakor, A and Iddrisu, H}, title = {Maternal depression does not affect complementary feeding indicators or stunting status of young children (6-23 months) in Northern Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {408}, pmid = {29941023}, issn = {1756-0500}, mesh = {Adult ; *Breast Feeding ; *Child Development ; Cross-Sectional Studies ; *Depression ; Female ; Ghana ; *Growth Disorders ; Humans ; Infant ; Infant Nutritional Physiological Phenomena ; Male ; Mothers/*psychology ; *Nutritional Status ; Young Adult ; }, abstract = {OBJECTIVE: Maternal depression may affect child feeding practice which is an important determinant of child nutritional status. The objective of this study was to explore the association between maternal depression and WHO complementary feeding indicators [minimum dietary diversity (MDD), minimum meal frequency (MMF) and minimum acceptable diet (MAD)] or stunting status of children (6-23 months) in Tamale Metropolis, Ghana. A community-based cross-sectional study was carried out involving 200 mother-child pairs randomly sampled from three communities in Tamale Metropolis, Ghana.

RESULTS: The prevalence of MDD, MMF, and MAD were 56.5, 65.0, and 44.0% respectively and 41.0% of the children sampled were stunted. A third of the mothers (33.5%) screened positive for depression. Maternal depression did not influence significantly MDD (p = 0.245), MMF (p = 0.442), and MAD (p = 0.885) or children's risk of stunting (p = 0.872). In conclusion maternal depression and child stunting are prevalent in Northern Ghana but there is a lack of evidence of an association between maternal depression and child feeding practices or nutritional status in this study population. Further research is needed to assess the effect of maternal depression on feeding practices and growth of young children.}, } @article {pmid29941015, year = {2018}, author = {Tadyanemhandu, C and Mupanda, C and Dambi, J and Chiwaridzo, M and Chikwasha, V and Chengetanai, S}, title = {Human immunodeficiency virus associated pulmonary conditions leading to hospital admission and the pulmonary rehabilitation services received by patients at two central hospitals in Harare.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {407}, pmid = {29941015}, issn = {1756-0500}, mesh = {Adult ; *Antiretroviral Therapy, Highly Active ; Cross-Sectional Studies ; Female ; HIV Infections/*complications/drug therapy ; *Hospitalization ; Humans ; Lung Diseases/*etiology/therapy ; Male ; Zimbabwe ; }, abstract = {OBJECTIVE: Use of highly active antiretroviral therapy has led to marked reductions in the incidence of HIV-associated opportunistic infections but has had comparatively less impact on the incidence of some pulmonary diseases. This study was done to determine the pulmonary conditions leading to hospital admissions in people living with HIV/AIDS at two central hospitals in Zimbabwe and the pulmonary rehabilitation intervention received.

RESULTS: A total of 92 participants were recruited of which 60 (65.2%) were females. The mean age of the participants was 41.3 years (SD = 9.1). The most common pulmonary condition leading to hospital admission was tuberculosis in 53 (57.6%). About 52 (56.6%) of the participants suffered from pulmonary complications in the last 6 months, 48 (92.3%) were admitted and 26 (50.0%) of the participants received physiotherapy treatment during their admission. None of the participants indicated that they once attended an outpatient pulmonary rehabilitation clinic. Respiratory complication is one of the leading causes of morbidity associated with HIV but no pulmonary rehabilitation services are being offered to these patients. There is need for introduction of pulmonary rehabilitation programs for people living with HIV/AIDS in the current setting.}, } @article {pmid29941013, year = {2018}, author = {Del Valle-Mendoza, J and Rojas-Jaimes, J and Vásquez-Achaya, F and Aguilar-Luis, MA and Correa-Nuñez, G and Silva-Caso, W and Lescano, AG and Song, X and Liu, Q and Li, D}, title = {Molecular identification of Bartonella bacilliformis in ticks collected from two species of wild mammals in Madre de Dios: Peru.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {405}, pmid = {29941013}, issn = {1756-0500}, support = {Contract 117-PNICP-PIAP-2015.//This work was supported by the Programa Nacional de Innovación para la Competitividad y Productividad (Innóvate Perú)/ ; contract N° 164-2016-FONDECYT.//This work was supported by Cienciativa of CONCYTEC Peru/ ; }, mesh = {Animals ; Bartonella Infections ; Bartonella bacilliformis/genetics/*isolation & purification ; Mammals ; Peru ; Ticks/*microbiology ; }, abstract = {OBJECTIVE: To study the presence of Bartonella bacilliformis in ticks collected from two wild mammals in Madre de Dios, Peru.

RESULTS: A total of 110 ticks were collected. Among the 43 Amblyomma spp. extracted from the 3 Tapirus terrestris only 3 were positive for B. bacilliformis. In addition, 12 out of the 67 Rhipicephalus (Boophilus) microplus obtained from the 3 Pecari tajacu were positive for B. bacilliformis. For the first time B. bacilliformis have been detected in arthropods other than Lutzomyia spp. Further studies are required to elucidate the possible role of ticks in the spread of South American Bartonellosis.}, } @article {pmid29940871, year = {2018}, author = {Chauhan, RD and Beyene, G and Taylor, NJ}, title = {Multiple morphogenic culture systems cause loss of resistance to cassava mosaic disease.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {132}, pmid = {29940871}, issn = {1471-2229}, support = {OPPGD1485//Bill and Melinda Gates Foundation/ ; OPP1152626//Bill and Melinda Gates Foundation/ ; }, abstract = {BACKGROUND: Morphogenic culture systems are central to crop improvement programs that utilize transgenic and genome editing technologies. We previously reported that CMD2-type cassava (Manihot esculenta) cultivars lose resistance to cassava mosaic disease (CMD) when passed through somatic embryogenesis. As a result, these plants cannot be developed as products for deployment where CMD is endemic such as sub-Saharan Africa or the Indian sub-continent.

RESULT: In order to increase understanding of this phenomenon, 21 African cassava cultivars were screened for resistance to CMD after regeneration through somatic embryogenesis. Fifteen cultivars were shown to retain resistance to CMD through somatic embryogenesis, confirming that the existing transformation and gene editing systems can be employed in these genetic backgrounds without compromising resistance to geminivirus infection. CMD2-type cultivars were also subjected to plant regeneration via caulogenesis and meristem tip culture, resulting in 25-36% and 5-10% of regenerated plant lines losing resistance to CMD respectively.

CONCLUSIONS: This study provides clear evidence that multiple morphogenic systems can result in loss of resistance to CMD, and that somatic embryogenesis per se is not the underlying cause of this phenomenon. The information described here is critical for interpreting genomic, transcriptomic and epigenomic datasets aimed at understanding CMD resistance mechanisms in cassava.}, } @article {pmid29940865, year = {2018}, author = {Muñoz-Sanhueza, LG and Lee, Y and Tillmann, M and Cohen, JD and Hvoslef-Eide, AK}, title = {Auxin analysis using laser microdissected plant tissues sections.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {133}, pmid = {29940865}, issn = {1471-2229}, support = {(IOS-1238812)//National Science Foundation/ ; }, abstract = {BACKGROUND: Quantitative measurement of actual auxin levels in plant tissue is complimentary to molecular methods measuring the expression of auxin related genes. Current analytical methods to quantify auxin have pushed the limit of detection to where auxin can be routinely quantified at the pictogram (pg) level, reducing the amount of tissue needed to perform these kinds of studies to amounts never imagined a few years ago. In parallel, the development of technologies like laser microdissection microscopy (LMD) has allowed specific cells to be harvested from discrete tissues without including adjacent cells. This method has gained popularity in recent years, especially for enabling a higher degree of spatial resolution in transcriptome profiling. As with other quantitative measurements, including hormone quantifications, sampling using traditional LMD is still challenging because sample preparation clearly compromises the preservation of analytes. Thus, we have developed and validated a sample preparation protocol combining cryosectioning, freeze-drying, and capturing with a laser microdissection microscope to provide high-quality and well-preserved plant materials suitable for ultrasensitive, spatially-resolved auxin quantification.

RESULTS: We developed a new method to provide discrete plant tissues for indole-3-acetic acid (IAA) quantification while preserving the plant tissue in the best possible condition to prevent auxin degradation. The method combines the use of cryosectioning, freeze-drying and LMD. The protocol may also be used for other applications that require small molecule analysis with high tissue-specificity where degradation of biological compounds may be an issue. It was possible to collect the equivalent to 15 mg of very specific tissue in approximately 4 h using LMD.

CONCLUSIONS: We have shown, by proof of concept, that freeze dried cryosections of plant tissue were suitable for LMD harvest and quantification of the phytohormone auxin using GC-MS/MS. We expect that the ability to resolve auxin levels with both spatial- and temporal resolution with high accuracy will enable experiments on complex processes, which will increase our knowledge of the many roles of auxins (and, in time, other phytohormones) in plant development.}, } @article {pmid29940863, year = {2018}, author = {Wei, S and Li, X and Gruber, MY and Feyissa, BA and Amyot, L and Hannoufa, A}, title = {COP9 signalosome subunit 5A affects phenylpropanoid metabolism, trichome formation and transcription of key genes of a regulatory tri-protein complex in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {134}, pmid = {29940863}, issn = {1471-2229}, support = {31370687,//National Natural Science Foundation of China/ ; 31770734//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Trichomes and phenylpropanoid-derived phenolics are structural and chemical protection against many adverse conditions. Their production is regulated by a network that includes a TTG1/bHLH/MYB tri-protein complex in Arabidopsis. CSN5a, encoding COP9 signalosome subunit 5a, has also been implicated in trichome and anthocyanin production; however, the regulatory roles of CSN5a in the processes through interaction with the tri-protein complex has yet to be investigated.

RESULTS: In this study, a new csn5a mutant, sk372, was recovered based on its altered morphological and chemical phenotypes compared to wild-type control. Mutant characterization was conducted with an emphasis on trichome and phenylpropanoid production and possible involvement of the tri-protein complex using metabolite and gene transcription profiling and scanning electron microscopy. Seed metabolite analysis revealed that defective CSN5a led to an enhanced production of many compounds in addition to anthocyanin, most notably phenylpropanoids and carotenoids as well as a glycoside of zeatin. Consistent changes in carotenoids and anthocyanin were also found in the sk372 leaves. In addition, 370 genes were differentially expressed in 10-day old seedlings of sk372 compared to its wild type control. Real-time transcript quantitative analysis showed that in sk372, GL2 and tri-protein complex gene TT2 was significantly suppressed (p < 0.05) while complex genes EGL3 and GL3 slightly decreased (p > 0.05). Complex genes MYB75, GL1 and flavonoid biosynthetic genes TT3 and TT18 in sk372 were all significantly enhanced. Overexpression of GL3 driven by cauliflower mosaic virus 35S promotor increased the number of single pointed trichomes only, no other phenotypic recovery in sk372.

CONCLUSIONS: Our results indicated clearly that COP9 signalosome subunit CSN5a affects trichome production and the metabolism of a wide range of phenylpropanoid and carotenoid compounds. Enhanced anthocyanin accumulation and reduced trichome production were related to the enhanced MYB75 and suppressed GL2 and some other differentially expressed genes associated with the TTG1/bHLH/MYB complexes.}, } @article {pmid29940862, year = {2018}, author = {LeBlanc, M and Zuber, V and Thompson, WK and Andreassen, OA and , and Frigessi, A and Andreassen, BK}, title = {A correction for sample overlap in genome-wide association studies in a polygenic pleiotropy-informed framework.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {494}, pmid = {29940862}, issn = {1471-2164}, support = {204623/Z/16/Z//Wellcome Trust/United Kingdom ; MC UU 00002/7//UK Medical Research Council/ ; }, mesh = {Case-Control Studies ; Computer Simulation ; Genome-Wide Association Study/*methods ; Genotype ; Humans ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: There is considerable evidence that many complex traits have a partially shared genetic basis, termed pleiotropy. It is therefore useful to consider integrating genome-wide association study (GWAS) data across several traits, usually at the summary statistic level. A major practical challenge arises when these GWAS have overlapping subjects. This is particularly an issue when estimating pleiotropy using methods that condition the significance of one trait on the signficance of a second, such as the covariate-modulated false discovery rate (cmfdr).

RESULTS: We propose a method for correcting for sample overlap at the summary statistic level. We quantify the expected amount of spurious correlation between the summary statistics from two GWAS due to sample overlap, and use this estimated correlation in a simple linear correction that adjusts the joint distribution of test statistics from the two GWAS. The correction is appropriate for GWAS with case-control or quantitative outcomes. Our simulations and data example show that without correcting for sample overlap, the cmfdr is not properly controlled, leading to an excessive number of false discoveries and an excessive false discovery proportion. Our correction for sample overlap is effective in that it restores proper control of the false discovery rate, at very little loss in power.

CONCLUSIONS: With our proposed correction, it is possible to integrate GWAS summary statistics with overlapping samples in a statistical framework that is dependent on the joint distribution of the two GWAS.}, } @article {pmid29940861, year = {2018}, author = {Fan, L and Wang, L and Wang, X and Zhang, H and Zhu, Y and Guo, J and Gao, W and Geng, H and Chen, Q and Qu, Y}, title = {A high-density genetic map of extra-long staple cotton (Gossypium barbadense) constructed using genotyping-by-sequencing based single nucleotide polymorphic markers and identification of fiber traits-related QTL in a recombinant inbred line population.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {489}, pmid = {29940861}, issn = {1471-2164}, support = {#2016B01001//Autonomous region key development projects/ ; }, mesh = {Chromosome Mapping ; Genome, Plant/genetics ; Genotype ; Gossypium/*genetics ; Microsatellite Repeats/genetics ; Polymorphism, Single Nucleotide/*genetics ; Quantitative Trait Loci/*genetics ; }, abstract = {BACKGROUND: Gossypium barbadense (Sea Island, Egyptian or Pima cotton) cotton has high fiber quality, however, few studies have investigated the genetic basis of its traits using molecular markers. Genome complexity reduction approaches such as genotyping-by-sequencing have been utilized to develop abundant markers for the construction of high-density genetic maps to locate quantitative trait loci (QTLs).

RESULTS: The Chinese G. barbadense cultivar 5917 and American Pima S-7 were used to develop a recombinant inbred line (RIL) population with 143 lines. The 143 RILs together with their parents were tested in three replicated field tests for lint yield traits (boll weight and lint percentage) and fiber quality traits (fiber length, fiber elongation, fiber strength, fiber uniformity and micronaire) and then genotyped using GBS to develop single-nucleotide polymorphism (SNP) markers. A high-density genetic map with 26 linkage groups (LGs) was constructed using 3557 GBS SNPs spanning a total genetic distance of 3076.23 cM at an average density of 1.09 cM between adjacent markers. A total of 42 QTLs were identified, including 24 QTLs on 12 LGs for fiber quality and 18 QTLs on 7 LGs for lint yield traits, with LG1 (9 QTLs), LG10 (7 QTLs) and LG14 (6 QTLs) carrying more QTLs. Common QTLs for the same traits and overlapping QTLs for different traits were detected. Each individual QTLs explained 0.97 to 20.7% of the phenotypic variation.

CONCLUSIONS: This study represents one of the first genetic mapping studies on the fiber quality and lint yield traits in a RIL population of G. barbadense using GBS-SNPs. The results provide important information for the subsequent fine mapping of QTLs and the prediction of candidate genes towards map-based cloning and marker-assisted selection in cotton.}, } @article {pmid29940860, year = {2018}, author = {Rainer, J and Meraviglia, V and Blankenburg, H and Piubelli, C and Pramstaller, PP and Paolin, A and Cogliati, E and Pompilio, G and Sommariva, E and Domingues, FS and Rossini, A}, title = {The arrhythmogenic cardiomyopathy-specific coding and non-coding transcriptome in human cardiac stromal cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {491}, pmid = {29940860}, issn = {1471-2164}, mesh = {Arrhythmias, Cardiac/*genetics ; Cardiomyopathies/*genetics ; Gene Expression Profiling/methods ; Genomics/methods ; Humans ; MicroRNAs/*genetics ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Arrhythmogenic cardiomyopathy (ACM) is a genetic autosomal disease characterized by abnormal cell-cell adhesion, cardiomyocyte death, progressive fibro-adipose replacement of the myocardium, arrhythmias and sudden death. Several different cell types contribute to the pathogenesis of ACM, including, as recently described, cardiac stromal cells (CStCs). In the present study, we aim to identify ACM-specific expression profiles of human CStCs derived from endomyocardial biopsies of ACM patients and healthy individuals employing TaqMan Low Density Arrays for miRNA expression profiling, and high throughput sequencing for gene expression quantification.

RESULTS: We identified 3 miRNAs and 272 genes as significantly differentially expressed at a 5% false discovery rate. Both the differentially expressed genes as well as the target genes of the ACM-specific miRNAs were found to be enriched in cell adhesion-related biological processes. Functional similarity and protein interaction-based network analyses performed on the identified deregulated genes, miRNA targets and known ACM-causative genes revealed clusters of highly related genes involved in cell adhesion, extracellular matrix organization, lipid transport and ephrin receptor signaling.

CONCLUSIONS: We determined for the first time the coding and non-coding transcriptome characteristic of ACM cardiac stromal cells, finding evidence for a potential contribution of miRNAs, specifically miR-29b-3p, to ACM pathogenesis or phenotype maintenance.}, } @article {pmid29940859, year = {2018}, author = {Ismagul, A and Yang, N and Maltseva, E and Iskakova, G and Mazonka, I and Skiba, Y and Bi, H and Eliby, S and Jatayev, S and Shavrukov, Y and Borisjuk, N and Langridge, P}, title = {A biolistic method for high-throughput production of transgenic wheat plants with single gene insertions.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {135}, pmid = {29940859}, issn = {1471-2229}, abstract = {BACKGROUND: The relatively low efficiency of biolistic transformation and subsequent integration of multiple copies of the introduced gene/s significantly complicate the genetic modification of wheat (Triticum aestivum) and other plant species. One of the key factors contributing to the reproducibility of this method is the uniformity of the DNA/gold suspension, which is dependent on the coating procedure employed. It was also shown recently that the relative frequency of single copy transgene inserts could be increased through the use of nanogram quantities of the DNA during coating.

RESULTS: A simplified DNA/gold coating method was developed to produce fertile transgenic plants, via microprojectile bombardment of callus cultures induced from immature embryos. In this method, polyethyleneglycol (PEG) and magnesium salt solutions were utilized in place of the spermidine and calcium chloride of the standard coating method, to precipitate the DNA onto gold microparticles. The prepared microparticles were used to generate transgenics from callus cultures of commercial bread wheat cv. Gladius resulting in an average transformation frequency of 9.9%. To increase the occurrence of low transgene copy number events, nanogram amounts of the minimal expression cassettes containing the gene of interest and the hpt gene were used for co-transformation. A total of 1538 transgenic wheat events were generated from 15,496 embryos across 19 independent experiments. The variation of single copy insert frequencies ranged from 16.1 to 73.5% in the transgenic wheat plants, which compares favourably to published results.

CONCLUSIONS: The DNA/gold coating procedure presented here allows efficient, large scale transformation of wheat. The use of nanogram amounts of vector DNA improves the frequency of single copy transgene inserts in transgenic wheat plants.}, } @article {pmid29940858, year = {2018}, author = {Baker, LA and Rosa, GJM and Hao, Z and Piazza, A and Hoffman, C and Binversie, EE and Sample, SJ and Muir, P}, title = {Multivariate genome-wide association analysis identifies novel and relevant variants associated with anterior cruciate ligament rupture risk in the dog model.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {39}, pmid = {29940858}, issn = {1471-2156}, support = {K01 OD019743/OD/NIH HHS/United States ; D13CA-020//Morris Animal Foundation/ ; NLMT15LM007359//U.S. National Library of Medicine/ ; K01OD019743-01A1//National Institutes of Health/ ; T32OD10999//National Institutes of Health/ ; }, abstract = {BACKGROUND: Anterior cruciate ligament rupture (ACLR) is a debilitating and potentially life-changing condition in humans, as there is a high prevalence of early-onset osteoarthritis after injury. Identification of high-risk individuals before they become patients is important, as post-treatment lifetime burden of ACLR in the USA ranges from $7.6 to $17.7 billion annually. ACLR is a complex disease with multiple risk factors including genetic predisposition. Naturally occurring ACLR in the dog is an excellent model for human ACLR, as risk factors and disease characteristics in humans and dogs are similar. In a univariate genome-wide association study (GWAS) of 237 Labrador Retrievers, we identified 99 ACLR candidate loci. It is likely that additional variants remain to be identified. Joint analysis of multiple correlated phenotypes is an underutilized technique that increases statistical power, even when only one phenotype is associated with the trait. Proximal tibial morphology has been shown to affect ACLR risk in both humans and dogs. In the present study, tibial plateau angle (TPA) and relative tibial tuberosity width (rTTW) were measured on bilateral radiographs from purebred Labrador Retrievers that were recruited to our initial GWAS. We performed a multivariate genome wide association analysis of ACLR status, TPA, and rTTW.

RESULTS: Our analysis identified 3 loci with moderate evidence of association that were not previously associated with ACLR. A locus on Chr1 associated with both ACLR and rTTW is located within ROR2, a gene important for cartilage and bone development. A locus on Chr4 associated with both ACLR and TPA resides within DOCK2, a gene that has been shown to promote immune cell migration and invasion in synovitis, an important predictor of ACLR. A third locus on Chr23 associated with only ACLR is located near a long non-coding RNA (lncRNA). LncRNA's are important for regulation of gene transcription and translation.

CONCLUSIONS: These results did not overlap with our previous GWAS, which is reflective of the different methods used, and supports the need for further work. The results of the present study are highly relevant to ACLR pathogenesis, and identify potential drug targets for medical treatment.}, } @article {pmid29940855, year = {2018}, author = {Aerts, N and de Bruijn, S and van Mourik, H and Angenent, GC and van Dijk, ADJ}, title = {Comparative analysis of binding patterns of MADS-domain proteins in Arabidopsis thaliana.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {131}, pmid = {29940855}, issn = {1471-2229}, abstract = {BACKGROUND: Correct flower formation requires highly specific temporal and spatial regulation of gene expression. In Arabidopsis thaliana the majority of the master regulators that determine flower organ identity belong to the MADS-domain transcription factor family. The canonical DNA binding motif for this transcription factor family is the CArG-box, which has the consensus CC(A/T)6GG. However, so far, a comprehensive analysis of MADS-domain binding patterns has not yet been performed.

RESULTS: Eight publicly available ChIP-seq datasets of MADS-domain proteins that regulate the floral transition and flower formation were analyzed. Surprisingly, the preferred DNA binding motif of each protein was a CArG-box with an NAA extension. Furthermore, motifs of other transcription factors were found in the vicinity of binding sites of MADS-domain transcription factors, suggesting that interaction of MADS-domain proteins with other transcription factors is important for target gene regulation. Finally, conservation of CArG-boxes between Arabidopsis ecotypes was assessed to obtain information about their evolutionary importance. CArG-boxes that fully matched the consensus were more conserved than other CArG-boxes, suggesting that the perfect CArG-box is evolutionary more important than other CArG-box variants.

CONCLUSION: Our analysis provides detailed insight into MADS-domain protein binding patterns. The results underline the importance of an extended version of the CArG-box and provide a first view on evolutionary conservation of MADS-domain protein binding sites in Arabidopsis ecotypes.}, } @article {pmid29940853, year = {2018}, author = {Wang, H and Zhao, S and Mao, K and Dong, Q and Liang, B and Li, C and Wei, Z and Li, M and Ma, F}, title = {Mapping QTLs for water-use efficiency reveals the potential candidate genes involved in regulating the trait in apple under drought stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {136}, pmid = {29940853}, issn = {1471-2229}, support = {31330068//Key Program of the National Natural Science Foundation of China/ ; CARS-28//China Agriculture Research System/ ; }, abstract = {BACKGROUND: Improvement of water-use efficiency (WUE) can effectively reduce production losses caused by drought stress. A better understanding of the genetic determination of WUE in crops under drought stress has great potential value for developing cultivars adapted to arid regions. To identify the genetic loci associated with WUE and reveal genes responsible for the trait in apple, we aim to map the quantitative trait loci (QTLs) for carbon isotope composition, the proxy for WUE, applying two contrasting irrigating regimes over the two-year experiment and search for the candidate genes encompassed in the mapped QTLs.

RESULTS: We constructed a high-density genetic linkage map with 10,172 markers of apple, using single nucleotide polymorphism (SNP) markers obtained through restriction site-associated DNA sequencing (RADseq) and a final segregating population of 350 seedlings from the cross of Honeycrisp and Qinguan. In total, 33 QTLs were identified for carbon isotope composition in apple under both well-watered and drought-stressed conditions. Three QTLs were stable over 2 years under drought stress on linkage groups LG8, LG15 and LG16, as validated by Kompetitive Allele-Specific PCR (KASP) assays. In those validated QTLs, 258 genes were screened according to their Gene Ontology functional annotations. Among them, 28 genes were identified, which exhibited significant responses to drought stress in 'Honeycrisp' and/or 'Qinguan'. These genes are involved in signaling, photosynthesis, response to stresses, carbohydrate metabolism, protein metabolism and modification, hormone metabolism and transport, transport, respiration, transcriptional regulation, and development regulation. They, especially those for photoprotection and relevant signal transduction, are potential candidate genes connected with WUE regulation in drought-stressed apple.

CONCLUSIONS: We detected three stable QTLs for carbon isotope composition in apple under drought stress over 2 years, and validated them by KASP assay. Twenty-eight candidate genes encompassed in these QTLs were identified. These stable genetic loci and series of genes provided here serve as a foundation for further studies on marker-assisted selection of high WUE and regulatory mechanism of WUE in apple exposed to drought conditions, respectively.}, } @article {pmid29940851, year = {2018}, author = {Xie, T and Chen, C and Li, C and Liu, J and Liu, C and He, Y}, title = {Genome-wide investigation of WRKY gene family in pineapple: evolution and expression profiles during development and stress.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {490}, pmid = {29940851}, issn = {1471-2164}, support = {31572089//National Natural Science Foundation of China/ ; 2013B020304002//Technology Commission of Guangdong Province/ ; 2016LM1128//Modern Agricultural Industry Technology System of Guangdong Province/ ; 2017KQNCX020//Foundation of Young Creative Talents in Higher Education of Guangdong Province/ ; }, mesh = {Ananas/*genetics ; *Evolution, Molecular ; Gene Expression Profiling ; Gene Expression Regulation, Plant/genetics ; Genome, Plant/*genetics ; Multigene Family/genetics ; Phylogeny ; Plant Proteins/*genetics ; }, abstract = {BACKGROUND: WRKY proteins comprise a large family of transcription factors that play important roles in many aspects of physiological processes and adaption to environment. However, little information was available about the WRKY genes in pineapple (Ananas comosus), an important tropical fruits. The recent release of the whole-genome sequence of pineapple allowed us to perform a genome-wide investigation into the organization and expression profiling of pineapple WRKY genes.

RESULTS: In the present study, 54 pineapple WRKY (AcWRKY) genes were identified and renamed on the basis of their respective chromosome distribution. According to their structural and phylogenetic features, the 54 AcWRKYs were further classified into three main groups with several subgroups. The segmental duplication events played a major role in the expansion of pineapple WRKY gene family. Synteny analysis and phylogenetic comparison of group III WRKY genes provided deep insight into the evolutionary characteristics of pineapple WRKY genes. Expression profiles derived from transcriptome data and real-time quantitative PCR analysis exhibited distinct expression patterns of AcWRKY genes in various tissues and in response to different abiotic stress and hormonal treatments.

CONCLUSIONS: Fifty four WRKY genes were identified in pineapple and the structure of their encoded proteins, their evolutionary characteristics and expression patterns were examined in this study. This systematic analysis provided a foundation for further functional characterization of WRKY genes with an aim of pineapple crop improvement.}, } @article {pmid29940850, year = {2018}, author = {Tang, X and Wang, Y and Zhang, Y and Huang, S and Liu, Z and Fei, D and Feng, H}, title = {A missense mutation of plastid RPS4 is associated with chlorophyll deficiency in Chinese cabbage (Brassica campestris ssp. pekinensis).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {130}, pmid = {29940850}, issn = {1471-2229}, support = {31672144//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Plastome mutants are ideal resources for elucidating the functions of plastid genes. Numerous studies have been conducted for the function of plastid genes in barley and tobacco; however, related information is limited in Chinese cabbage.

RESULTS: A chlorophyll-deficient mutant of Chinese cabbage that was derived by ethyl methanesulfonate treatment on isolated microspores showed uniformly pale green inner leaves and slow growth compared with that shown by the wild type "Fukuda 50' ('FT'). Genetic analysis revealed that cdm was cytoplasmically inherited. Physiological and ultrastructural analyses of cdm showed impaired photosynthesis and abnormal chloroplast development. Utilizing next generation sequencing, the complete plastomes of cdm and 'FT' were respectively re-mapped to the reference genome of Chinese cabbage, and an A-to-C base substitution with a mutation ratio higher than 99% was detected. The missense mutation of plastid ribosomal protein S4 led to valine substitution for glycine at residue 193. The expression level of rps4 was analyzed using quantitative real-time PCR and found lower in than in 'FT'. RNA gel-blot assays showed that the abundance of mature 23S rRNA, 16S rRNA, 5S rRNA, and 4.5S rRNA significantly decreased and that the processing of 23S, 16S rRNA, and 4.5S rRNA was seriously impaired, affecting the ribosomal function in cdm.

CONCLUSIONS: These findings indicated that cdm was a plastome mutant and that chlorophyll deficiency might be due to an A-to-C base substitution of the plastome-encoded rps4 that impaired the rRNA processing and affected the ribosomal function.}, } @article {pmid29940849, year = {2018}, author = {Metzger, J and Rau, J and Naccache, F and Bas Conn, L and Lindgren, G and Distl, O}, title = {Genome data uncover four synergistic key regulators for extremely small body size in horses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {492}, pmid = {29940849}, issn = {1471-2164}, mesh = {Animals ; Body Size/genetics/*physiology ; Equidae ; Genomics/*methods ; Genotype ; High-Throughput Nucleotide Sequencing/methods ; Horses ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: Miniature size in horses represents an extreme reduction of withers height that originated after domestication. In some breeds, it is a highly desired trait representing a breed- or subtype-specific feature. The genomic changes that emerged due to strong-targeted selection towards this distinct type remain unclear.

RESULTS: Comparisons of whole-genome sequencing data from two Miniature Shetland ponies and one standard-sized Shetland pony, performed to elucidate genetic determinants for miniature size, revealed four synergistic variants, limiting withers height to 34.25 in. (87 cm). Runs of homozygosity regions were detected spanning these four variants in both the Miniature Shetland ponies and the standard-sized Shetland pony. They were shown to be characteristic of the Shetland pony breed, resulting in a miniature type under specific genotypic combinations. These four genetic variants explained 72% of the size variation among Shetland ponies and related breeds. The length of the homozygous regions indicate that they arose over 1000 years ago. In addition, a copy number variant was identified in DIAPH3 harboring a loss exclusively in ponies and donkeys and thus representing a potential height-associated variant.

CONCLUSION: This study reveals main drivers for miniature size in horses identified in whole genome data and thus provides relevant candidate genes for extremely short stature in mammals.}, } @article {pmid29940847, year = {2018}, author = {Tom, N and Tom, O and Malcikova, J and Pavlova, S and Kubesova, B and Rausch, T and Kolarik, M and Benes, V and Bystry, V and Pospisilova, S}, title = {ToTem: a tool for variant calling pipeline optimization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {243}, pmid = {29940847}, issn = {1471-2105}, abstract = {BACKGROUND: High-throughput bioinformatics analyses of next generation sequencing (NGS) data often require challenging pipeline optimization. The key problem is choosing appropriate tools and selecting the best parameters for optimal precision and recall.

RESULTS: Here we introduce ToTem, a tool for automated pipeline optimization. ToTem is a stand-alone web application with a comprehensive graphical user interface (GUI). ToTem is written in Java and PHP with an underlying connection to a MySQL database. Its primary role is to automatically generate, execute and benchmark different variant calling pipeline settings. Our tool allows an analysis to be started from any level of the process and with the possibility of plugging almost any tool or code. To prevent an over-fitting of pipeline parameters, ToTem ensures the reproducibility of these by using cross validation techniques that penalize the final precision, recall and F-measure. The results are interpreted as interactive graphs and tables allowing an optimal pipeline to be selected, based on the user's priorities. Using ToTem, we were able to optimize somatic variant calling from ultra-deep targeted gene sequencing (TGS) data and germline variant detection in whole genome sequencing (WGS) data.

CONCLUSIONS: ToTem is a tool for automated pipeline optimization which is freely available as a web application at https://totem.software .}, } @article {pmid29940845, year = {2018}, author = {Jambusaria, A and Klomp, J and Hong, Z and Rafii, S and Dai, Y and Malik, AB and Rehman, J}, title = {A computational approach to identify cellular heterogeneity and tissue-specific gene regulatory networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {217}, pmid = {29940845}, issn = {1471-2105}, support = {R01-GM094220/NH/NIH HHS/United States ; P01 HL077806/HL/NHLBI NIH HHS/United States ; P01-HL060678/NH/NIH HHS/United States ; T32-HL007829/NH/NIH HHS/United States ; R01-HL090152/NH/NIH HHS/United States ; R01-HL118068/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: The heterogeneity of cells across tissue types represents a major challenge for studying biological mechanisms as well as for therapeutic targeting of distinct tissues. Computational prediction of tissue-specific gene regulatory networks may provide important insights into the mechanisms underlying the cellular heterogeneity of cells in distinct organs and tissues.

RESULTS: Using three pathway analysis techniques, gene set enrichment analysis (GSEA), parametric analysis of gene set enrichment (PGSEA), alongside our novel model (HeteroPath), which assesses heterogeneously upregulated and downregulated genes within the context of pathways, we generated distinct tissue-specific gene regulatory networks. We analyzed gene expression data derived from freshly isolated heart, brain, and lung endothelial cells and populations of neurons in the hippocampus, cingulate cortex, and amygdala. In both datasets, we found that HeteroPath segregated the distinct cellular populations by identifying regulatory pathways that were not identified by GSEA or PGSEA. Using simulated datasets, HeteroPath demonstrated robustness that was comparable to what was seen using existing gene set enrichment methods. Furthermore, we generated tissue-specific gene regulatory networks involved in vascular heterogeneity and neuronal heterogeneity by performing motif enrichment of the heterogeneous genes identified by HeteroPath and linking the enriched motifs to regulatory transcription factors in the ENCODE database.

CONCLUSIONS: HeteroPath assesses contextual bidirectional gene expression within pathways and thus allows for transcriptomic assessment of cellular heterogeneity. Unraveling tissue-specific heterogeneity of gene expression can lead to a better understanding of the molecular underpinnings of tissue-specific phenotypes.}, } @article {pmid29940844, year = {2018}, author = {Zahoor, M and Shafiq, S and Ullah, H and Sadiq, A and Ullah, F}, title = {Isolation of quercetin and mandelic acid from Aesculus indica fruit and their biological activities.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {5}, pmid = {29940844}, issn = {1471-2091}, mesh = {Acetylcholinesterase/drug effects ; Antioxidants/*pharmacology ; Butyrylcholinesterase/drug effects ; Cholinesterase Inhibitors/*pharmacology ; Chromatography, High Pressure Liquid ; Flavonoids/analysis ; Hippocastanaceae/*chemistry ; Mandelic Acids/*isolation & purification/*pharmacology ; Oxidative Stress/drug effects ; Phenols/analysis ; Proton Magnetic Resonance Spectroscopy ; Quercetin/*isolation & purification/*pharmacology ; Reactive Oxygen Species/metabolism ; Spectroscopy, Fourier Transform Infrared ; }, abstract = {BACKGROUND: In this study Aesculus indica fruit was subjected to isolation of phytochemicals. Two antioxidants quercetin and Mandelic acid were isolated in pure state. The free radical scavenging and acetyl choline esterase inhibitory potential of the crude extract and sub fractions were also determined.

RESULTS: The antioxidant capacity of crude extract, fractions and isolated compounds were determined by DPPH and ABTS methods. Folin-Ciocalteu reagent method was used to estimate the total phenolic contents and were found to be 78.34 ± 0.96, 44.16 ± 1.05, 65.45 ± 1.29, 37.85 ± 1.44 and 50.23 ± 2.431 (mg/g of gallic acid) in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fractions respectively. The flavonoid concentration in crude extract, ethyl acetate, chloroform, n-hexane and aqueous fraction were; 85.30 ± 1.20, 53.80 ± 1.07, 77.50 ± 1.12, 26.30 ± 1.35 and 37.78 ± 1.25 (mg/g of quercetin) respectively. The chloroform fraction was more potent against enzymes, acetyl choline esterase and butyryl choline esterase (IC50 = 85 and 160 μg/ml respectively). The phenolic compounds in the crude extract and fractions were determined using HPLC standard method. Chlorogenic acid, quercetin, phloroglucinol, rutin, mandelic acid and hydroxy benzoic acid were detected at retention times 6.005, 10.062, 22.623, 30.597, 35.490 and 36.211 in crude extract and different fractions. The ethyl acetate fraction was rich in the targeted compounds and was therefore subjected to column isolation. The HPLC chromatogram of isolated compounds showed single peak at specified retention times which confirms their isolation in pure state. The isolated compounds were then characterized by FTIR and NMR spectrophotometric techniques.

CONCLUSION: The Aesculus indica fruit extracts showed antioxidant and anticholine esterase inhibitory potentials. Two bioactive compounds were isolated in the pure form ethyl acetate fraction. From results it was concluded that the fruit of this plant could be used to minimize oxidative stress caused by reactive oxygen species.}, } @article {pmid29940843, year = {2018}, author = {Gu, M and Buckley, M}, title = {Semi-supervised machine learning for automated species identification by collagen peptide mass fingerprinting.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {241}, pmid = {29940843}, issn = {1471-2105}, abstract = {BACKGROUND: Biomolecular methods for species identification are increasingly being utilised in the study of changing environments, both at the microscopic and macroscopic levels. High-throughput peptide mass fingerprinting has been largely applied to bacterial identification, but increasingly used to identify archaeological and palaeontological skeletal material to yield information on past environments and human-animal interaction. However, as applications move away from predominantly domesticate and the more abundant wild fauna to a much wider range of less common taxa that do not yet have genetically-derived sequence information, robust methods of species identification and biomarker selection need to be determined.

RESULTS: Here we developed a supervised machine learning algorithm for classifying the species of ancient remains based on collagen fingerprinting. The aim was to minimise requirements on prior knowledge of known species while yielding satisfactory sensitivity and specificity. The algorithm uses iterations of a modified random forest classifier with a similarity scoring system to expand its identified samples. We tested it on a set of 6805 spectra and found that a high level of accuracy can be achieved with a training set of five identified specimens per taxon.

CONCLUSIONS: This method consistently achieves higher accuracy than two-dimensional principal component analysis and similar accuracy with hierarchical clustering using optimised parameters, which greatly reduces requirements for human input. Within the vertebrata, we demonstrate that this method was able to achieve the taxonomic resolution of family or sub-family level whereas the genus- or species-level identification may require manual interpretation or further experiments. In addition, it also identifies additional species biomarkers than those previously published.}, } @article {pmid29940842, year = {2018}, author = {Ausmees, K and John, A and Toor, SZ and Hellander, A and Nettelblad, C}, title = {BAMSI: a multi-cloud service for scalable distributed filtering of massive genome data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {240}, pmid = {29940842}, issn = {1471-2105}, abstract = {BACKGROUND: The advent of next-generation sequencing (NGS) has made whole-genome sequencing of cohorts of individuals a reality. Primary datasets of raw or aligned reads of this sort can get very large. For scientific questions where curated called variants are not sufficient, the sheer size of the datasets makes analysis prohibitively expensive. In order to make re-analysis of such data feasible without the need to have access to a large-scale computing facility, we have developed a highly scalable, storage-agnostic framework, an associated API and an easy-to-use web user interface to execute custom filters on large genomic datasets.

RESULTS: We present BAMSI, a Software as-a Service (SaaS) solution for filtering of the 1000 Genomes phase 3 set of aligned reads, with the possibility of extension and customization to other sets of files. Unique to our solution is the capability of simultaneously utilizing many different mirrors of the data to increase the speed of the analysis. In particular, if the data is available in private or public clouds - an increasingly common scenario for both academic and commercial cloud providers - our framework allows for seamless deployment of filtering workers close to data. We show results indicating that such a setup improves the horizontal scalability of the system, and present a possible use case of the framework by performing an analysis of structural variation in the 1000 Genomes data set.

CONCLUSIONS: BAMSI constitutes a framework for efficient filtering of large genomic data sets that is flexible in the use of compute as well as storage resources. The data resulting from the filter is assumed to be greatly reduced in size, and can easily be downloaded or routed into e.g. a Hadoop cluster for subsequent interactive analysis using Hive, Spark or similar tools. In this respect, our framework also suggests a general model for making very large datasets of high scientific value more accessible by offering the possibility for organizations to share the cost of hosting data on hot storage, without compromising the scalability of downstream analysis.}, } @article {pmid29940841, year = {2018}, author = {García-Pérez, CA and Guo, X and Navarro, JG and Aguilar, DAG and Lara-Ramírez, EE}, title = {Proteome-wide analysis of human motif-domain interactions mapped on influenza a virus.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {238}, pmid = {29940841}, issn = {1471-2105}, abstract = {BACKGROUND: The influenza A virus (IAV) is a constant threat for humans worldwide. The understanding of motif-domain protein participation is essential to combat the pathogen.

RESULTS: In this study, a data mining approach was employed to extract influenza-human Protein-Protein interactions (PPI) from VirusMentha,Virus MINT, IntAct, and Pfam databases, to mine motif-domain interactions (MDIs) stored as Regular Expressions (RegExp) in 3DID database. A total of 107 RegExp related to human MDIs were searched on 51,242 protein fragments from H1N1, H1N2, H2N2, H3N2 and H5N1 strains obtained from Virus Variation database. A total 46 MDIs were frequently mapped on the IAV proteins and shared between the different strains. IAV kept host-like MDIs that were associated with the virus survival, which could be related to essential biological process such as microtubule-based processes, regulation of cell cycle check point, regulation of replication and transcription of DNA, etc. in human cells. The amino acid motifs were searched for matches in the immune epitope database and it was found that some motifs are part of experimentally determined epitopes on IAV, implying that such interactions exist.

CONCLUSION: The directed data-mining method employed could be used to identify functional motifs in other viruses for envisioning new therapies.}, } @article {pmid29940840, year = {2018}, author = {Matey-Hernandez, ML and , and Brunak, S and Izarzugaza, JMG}, title = {Benchmarking the HLA typing performance of Polysolver and Optitype in 50 Danish parental trios.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {239}, pmid = {29940840}, issn = {1471-2105}, abstract = {BACKGROUND: The adaptive immune response intrinsically depends on hypervariable human leukocyte antigen (HLA) genes. Concomitantly, correct HLA phenotyping is crucial for successful donor-patient matching in organ transplantation. The cost and technical limitations of current laboratory techniques, together with advances in next-generation sequencing (NGS) methodologies, have increased the need for precise computational typing methods.

RESULTS: We tested two widespread HLA typing methods using high quality full genome sequencing data from 150 individuals in 50 family trios from the Genome Denmark project. First, we computed descendant accuracies assessing the agreement in the inheritance of alleles from parents to offspring. Second, we compared the locus-specific homozygosity rates as well as the allele frequencies; and we compared those to the observed values in related populations. We provide guidelines for testing the accuracy of HLA typing methods by comparing family information, which is independent of the availability of curated alleles.

CONCLUSIONS: Although current computational methods for HLA typing generally provide satisfactory results, our benchmark - using data with ultra-high sequencing depth - demonstrates the incompleteness of current reference databases, and highlights the importance of providing genomic databases addressing current sequencing standards, a problem yet to be resolved before benefiting fully from personalised medicine approaches HLA phenotyping is essential.}, } @article {pmid29940839, year = {2018}, author = {Korejo, NA and Wei, Q and Zheng, K and Mao, D and Korejo, RA and Shah, AH and Shi, F}, title = {Contemporaneous effects of diabetes mellitus and hypothyroidism on spermatogenesis and immunolocalization of Claudin-11 inside the seminiferous tubules of mice.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {15}, pmid = {29940839}, issn = {1471-213X}, support = {31572403//National Natural Science Foundation of China/International ; }, abstract = {BACKGROUND: Diabetes and hypothyroidism produce adverse effects on body weight and sexual maturity by inhibiting body growth and metabolism. The occurrence of diabetes is always accompanied with thyroid dysfunction. Thus, it is important to take hypo- or hyper-thyroidism into consideration when exploring the adverse effects caused by diabetes. Previous reports have found hypothyroidism inhibits testicular growth by delaying Sertoli cell differentiation and proliferation. Hence, by establishing a mouse model of diabetes combined with hypothyroidism, we provided evidence that poly glandular autoimmune syndrome affected testicular development and spermatogenesis.

RESULTS: we mimicked polyglandular deficiency syndrome in both immature and prepubertal mice by induction of diabetes and hypothyroidism, which caused decreases in serum concentrations of testosterone and insulin like growth factor 1 (IGF-1). Such reduction of growth factor resulted in inhibition of testicular and epididymal development. Moreover, expressions of Claudin-11 were observed between Sertoli cells and disrupted in the testes of syndrome group mice. We also found reduced sperm count and motility in prepubertal mice.

CONCLUSIONS: This mimicry of the diabetes and thyroid dysfunction, will be helpful to better understand the reasons for male infertility in diabetic-cum-hypothyroid patients.}, } @article {pmid29940838, year = {2018}, author = {Ren, Y and Sarkar, A and Kahveci, T}, title = {ProMotE: an efficient algorithm for counting independent motifs in uncertain network topologies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {242}, pmid = {29940838}, issn = {1471-2105}, abstract = {BACKGROUND: Identifying motifs in biological networks is essential in uncovering key functions served by these networks. Finding non-overlapping motif instances is however a computationally challenging task. The fact that biological interactions are uncertain events further complicates the problem, as it makes the existence of an embedding of a given motif an uncertain event as well.

RESULTS: In this paper, we develop a novel method, ProMotE (Probabilistic Motif Embedding), to count non-overlapping embeddings of a given motif in probabilistic networks. We utilize a polynomial model to capture the uncertainty. We develop three strategies to scale our algorithm to large networks.

CONCLUSIONS: Our experiments demonstrate that our method scales to large networks in practical time with high accuracy where existing methods fail. Moreover, our experiments on cancer and degenerative disease networks show that our method helps in uncovering key functional characteristics of biological networks.}, } @article {pmid29940837, year = {2018}, author = {Song, S and Yang, M and Li, Y and Rouzi, M and Zhao, Q and Pu, Y and He, X and Mwacharo, JM and Yang, N and Ma, Y and Jiang, L}, title = {Genome-wide discovery of lincRNAs with spatiotemporal expression patterns in the skin of goat during the cashmere growth cycle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {495}, pmid = {29940837}, issn = {1471-2164}, support = {31472064//National Natural Science Foundation of China/ ; 31601910//National Natural Science Foundation of China/ ; 201303059//the Special Fund for Agro-scientific Research in the Public Interest/ ; CARS-40-01//the earmarked fund for Modern Agro-industry Technology Research System/ ; ASTIP-IAS01//Agricultural Science and Technology Innovation Program of China/ ; }, mesh = {Animals ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/genetics/physiology ; Goats ; Hair Follicle/metabolism/*physiology ; RNA, Long Noncoding/genetics/*physiology ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Long intergenic noncoding RNAs (lincRNAs) have been recognized in recent years as key regulators of biological processes. However, lincRNAs in goat remain poorly characterized both across various tissues and during different developmental stages in goat (Capra hircus).

RESULTS: We performed the genome-wide discovery of the lincRNAs in goat by combining the RNA-seq dataset that were generated from 28 cashmere goat skin samples and the 12 datasets of goat tissues downloaded from the NCBI database. We identified a total of 5546 potential lincRNA transcripts that overlapped 3641 lincRNA genes. These lincRNAs exhibited a tissue-specific pattern. Specifically, there are 584 lincRNAs expressed exclusively in only one tissue, and 91 were highly expressed in hair follicle (HF). In addition, 2350 protein-coding genes and 492 lincRNAs were differentially expressed in the skin of goat. The majority exhibited the remarkable differential expression during the transition of the goat skin from the May-June to August-October time point, which covered the different seasons. Fundamental biological processes, such as skin development, were significantly enriched in these genes. Furthermore, we identified several lincRNAs highly expressed in the HF, which exhibited not only the co-expression pattern with the key factors to the HF development but also the activated expression in the August to October time point. Intriguingly, one of spatiotemporal lincRNAs, linc-chig1598 could be a potential regulator of distal-less homeobox 3 expression during the secondary hair follicle growth.

CONCLUSIONS: This study will facilitate future studies aimed at unravelling the function of lincRNAs in hair follicle development.}, } @article {pmid29940836, year = {2018}, author = {Ning, Q and Zhao, X and Bao, L and Ma, Z and Zhao, X}, title = {Detecting Succinylation sites from protein sequences using ensemble support vector machine.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {237}, pmid = {29940836}, issn = {1471-2105}, abstract = {BACKGROUND: Lysine succinylation is a new kind of post-translational modification which plays a key role in protein conformation regulation and cellular function control. To understand the mechanism of succinylation profoundly, it is necessary to identify succinylation sites in proteins accurately. However, traditional methods, experimental approaches, are labor-intensive and time-consuming. Computational prediction methods have been proposed recent years, and they are popular because of their convenience and high speed. In this study, we developed a new method to predict succinylation sites in protein combining multiple features, including amino acid composition, binary encoding, physicochemical property and grey pseudo amino acid composition, with a feature selection scheme (information gain). And then, it was trained using SVM (Support Vector Machine) and an ensemble learning algorithm.

RESULTS: The performance of this method was measured with an accuracy of 89.14% and a MCC (Matthew Correlation Coefficient) of 0.79 using 10-fold cross validation on training dataset and an accuracy of 84.5% and a MCC of 0.2 on independent dataset.

CONCLUSIONS: The conclusions made from this study can help to understand more of the succinylation mechanism. These results suggest that our method was very promising for predicting succinylation sites. The source code and data of this paper are freely available at https://github.com/ningq669/PSuccE .}, } @article {pmid29940835, year = {2018}, author = {Devlin, JC and Battaglia, T and Blaser, MJ and Ruggles, KV}, title = {WHAM!: a web-based visualization suite for user-defined analysis of metagenomic shotgun sequencing data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {493}, pmid = {29940835}, issn = {1471-2164}, support = {U01 AI22285//Foundation for the National Institutes of Health/ ; }, mesh = {Computational Biology/*methods ; High-Throughput Nucleotide Sequencing/methods ; Metagenomics/*methods ; Microbiota/*genetics ; }, abstract = {BACKGROUND: Exploration of large data sets, such as shotgun metagenomic sequence or expression data, by biomedical experts and medical professionals remains as a major bottleneck in the scientific discovery process. Although tools for this purpose exist for 16S ribosomal RNA sequencing analysis, there is a growing but still insufficient number of user-friendly interactive visualization workflows for easy data exploration and figure generation. The development of such platforms for this purpose is necessary to accelerate and streamline microbiome laboratory research.

RESULTS: We developed the Workflow Hub for Automated Metagenomic Exploration (WHAM!) as a web-based interactive tool capable of user-directed data visualization and statistical analysis of annotated shotgun metagenomic and metatranscriptomic data sets. WHAM! includes exploratory and hypothesis-based gene and taxa search modules for visualizing differences in microbial taxa and gene family expression across experimental groups, and for creating publication quality figures without the need for command line interface or in-house bioinformatics.

CONCLUSIONS: WHAM! is an interactive and customizable tool for downstream metagenomic and metatranscriptomic analysis providing a user-friendly interface allowing for easy data exploration by microbiome and ecological experts to facilitate discovery in multi-dimensional and large-scale data sets.}, } @article {pmid29940834, year = {2018}, author = {Veiga, RV and Barbosa, HJC and Bernardino, HS and Freitas, JM and Feitosa, CA and Matos, SMA and Alcântara-Neves, NM and Barreto, ML}, title = {Multiobjective grammar-based genetic programming applied to the study of asthma and allergy epidemiology.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {245}, pmid = {29940834}, issn = {1471-2105}, support = {072405/Z/03/Z//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Asthma and allergies prevalence increased in recent decades, being a serious global health problem. They are complex diseases with strong contextual influence, so that the use of advanced machine learning tools such as genetic programming could be important for the understanding the causal mechanisms explaining those conditions. Here, we applied a multiobjective grammar-based genetic programming (MGGP) to a dataset composed by 1047 subjects. The dataset contains information on the environmental, psychosocial, socioeconomics, nutritional and infectious factors collected from participating children. The objective of this work is to generate models that explain the occurrence of asthma, and two markers of allergy: presence of IgE antibody against common allergens, and skin prick test positivity for common allergens (SPT).

RESULTS: The average of the accuracies of the models for asthma higher in MGGP than C4.5. IgE were higher in MGGP than in both, logistic regression and C4.5. MGGP had levels of accuracy similar to RF, but unlike RF, MGGP was able to generate models that were easy to interpret.

CONCLUSIONS: MGGP has shown that infections, psychosocial, nutritional, hygiene, and socioeconomic factors may be related in such an intricate way, that could be hardly detected using traditional regression based epidemiological techniques. The algorithm MGGP was implemented in c ++ and is available on repository: http://bitbucket.org/ciml-ufjf/ciml-lib .}, } @article {pmid29940833, year = {2018}, author = {Kagaris, D and Khamesipour, A and Yiannoutsos, CT}, title = {AUCTSP: an improved biomarker gene pair class predictor.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {244}, pmid = {29940833}, issn = {1471-2105}, abstract = {BACKGROUND: The Top Scoring Pair (TSP) classifier, based on the concept of relative ranking reversals in the expressions of pairs of genes, has been proposed as a simple, accurate, and easily interpretable decision rule for classification and class prediction of gene expression profiles. The idea that differences in gene expression ranking are associated with presence or absence of disease is compelling and has strong biological plausibility. Nevertheless, the TSP formulation ignores significant available information which can improve classification accuracy and is vulnerable to selecting genes which do not have differential expression in the two conditions ("pivot" genes).

RESULTS: We introduce the AUCTSP classifier as an alternative rank-based estimator of the magnitude of the ranking reversals involved in the original TSP. The proposed estimator is based on the Area Under the Receiver Operating Characteristic (ROC) Curve (AUC) and as such, takes into account the separation of the entire distribution of gene expression levels in gene pairs under the conditions considered, as opposed to comparing gene rankings within individual subjects as in the original TSP formulation. Through extensive simulations and case studies involving classification in ovarian, leukemia, colon, breast and prostate cancers and diffuse large b-cell lymphoma, we show the superiority of the proposed approach in terms of improving classification accuracy, avoiding overfitting and being less prone to selecting non-informative (pivot) genes.

CONCLUSIONS: The proposed AUCTSP is a simple yet reliable and robust rank-based classifier for gene expression classification. While the AUCTSP works by the same principle as TSP, its ability to determine the top scoring gene pair based on the relative rankings of two marker genes across all subjects as opposed to each individual subject results in significant performance gains in classification accuracy. In addition, the proposed method tends to avoid selection of non-informative (pivot) genes as members of the top-scoring pair.}, } @article {pmid29940256, year = {2018}, author = {Munro, C and Siebert, S and Zapata, F and Howison, M and Damian-Serrano, A and Church, SH and Goetz, FE and Pugh, PR and Haddock, SHD and Dunn, CW}, title = {Improved phylogenetic resolution within Siphonophora (Cnidaria) with implications for trait evolution.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {823-833}, pmid = {29940256}, issn = {1095-9513}, support = {P30 RR031153/RR/NCRR NIH HHS/United States ; }, abstract = {Siphonophores are a diverse group of hydrozoans (Cnidaria) that are found at most depths of the ocean - from the surface, like the familiar Portuguese man of war, to the deep sea. They play important roles in ocean ecosystems, and are among the most abundant gelatinous predators. A previous phylogenetic study based on two ribosomal RNA genes provided insight into the internal relationships between major siphonophore groups. There was, however, little support for many deep relationships within the clade Codonophora. Here, we present a new siphonophore phylogeny based on new transcriptome data from 29 siphonophore species analyzed in combination with 14 publicly available genomic and transcriptomic datasets. We use this new phylogeny to reconstruct several traits that are central to siphonophore biology, including sexual system (monoecy vs. dioecy), gain and loss of zooid types, life history traits, and habitat. The phylogenetic relationships in this study are largely consistent with the previous phylogeny, but we find strong support for new clades within Codonophora that were previously unresolved. These results have important implications for trait evolution within Siphonophora, including favoring the hypothesis that monoecy arose at least twice.}, } @article {pmid29940142, year = {2018}, author = {Tang, JLY and Guo, Y and Stockdale, WT and Rana, K and Killen, AC and Mommersteeg, MTM and Yamamoto, Y}, title = {The developmental origin of heart size and shape differences in Astyanax mexicanus populations.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {272-284}, pmid = {29940142}, issn = {1095-564X}, support = {PG/12/39/29626//British Heart Foundation/United Kingdom ; }, mesh = {Animals ; *Characiformes/embryology/genetics ; *Crosses, Genetic ; *Evolution, Molecular ; Genome/*physiology ; Heart/*embryology ; Heart Rate/*physiology ; Humans ; Organ Size ; }, abstract = {Regulation of heart size and shape is one of the least understood processes in developmental biology. We have for the first time analysed the hearts of Astyanax mexicanus and identified several differences in heart morphology between the surface (epigean morph) and cave-dwelling (troglomorph) morphs. Examination of the adult revealed that the troglomorph possesses a smaller heart with a rounder ventricle in comparison to the epigean morph. The size differences identified appear to arise early in development, as early as 24 h post-fertilisation (hpf), while shape differences begin to appear at 2 days post-fertilisation. The heart of the first-generation cross between the cave-dwelling and river-dwelling morph shows uncoupling of different phenotypes observed in the parental populations and indicates that the cardiac differences have become embedded in the genome during evolution. The differences in heart morphology are accompanied by functional changes between the two morphs, with the cave-dwelling morph exhibiting a slower heart rate than the river-dwelling morph. The identification of morphological and functional differences in the A. mexicanus heart could allow us to gain more insight into how such parameters are regulated during cardiac development, with potential relevance to cardiac pathologies in humans.}, } @article {pmid29939310, year = {2018}, author = {Long, H and Miller, SF and Williams, E and Lynch, M}, title = {Specificity of the DNA Mismatch Repair System (MMR) and Mutagenesis Bias in Bacteria.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2414-2421}, pmid = {29939310}, issn = {1537-1719}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; R35 GM122566/GM/NIGMS NIH HHS/United States ; }, abstract = {The mutation rate of an organism is influenced by the interaction of evolutionary forces such as natural selection and genetic drift. However, the mutation spectrum (i.e., the frequency distribution of different types of mutations) can be heavily influenced by DNA repair. Using mutation-accumulation lines of the extremophile bacterium Deinococcus radiodurans ΔmutS1 and the model soil bacterium Pseudomonas fluorescens wild-type and MMR- (Methyl-dependent Mismatch Repair-deficient) strains, we report the mutational features of these two important bacteria. We find that P. fluorescens has one of the highest MMR repair efficiencies among tested bacteria. We also discover that MMR of D. radiodurans preferentially repairs deletions, contrary to all other bacteria examined. We then, for the first time, quantify genome-wide efficiency and specificity of MMR in repairing different genomic regions and mutation types, by evaluating the P. fluorescens and D. radiodurans mutation data sets, along with previously reported ones of Bacillus subtilis subsp. subtilis, Escherichia coli, Vibrio cholerae, and V. fischeri. MMR in all six bacteria shares two general features: 1) repair efficiency is influenced by the neighboring base composition for both transitions and transversions, not limited to transversions as previously reported; and 2) MMR only recognizes indels <4 bp in length. This study demonstrates the power of mutation accumulation lines in quantifying DNA repair and mutagenesis patterns.}, } @article {pmid29939247, year = {2018}, author = {Männistö, M and Vuosku, J and Stark, S and Saravesi, K and Suokas, M and Markkola, A and Martz, F and Rautio, P}, title = {Bacterial and fungal communities in boreal forest soil are insensitive to changes in snow cover conditions.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy123}, pmid = {29939247}, issn = {1574-6941}, abstract = {The northern regions are experiencing considerable changes in winter climate leading to more frequent warm periods, rain-on-snow events and reduced snow pack diminishing the insulation properties of snow cover and increasing soil frost and freeze-thaw cycles. In this study, we investigated how the lack of snow cover, formation of ice encasement and snow compaction affect the size, structure and activities of soil bacterial and fungal communities. Contrary to our hypotheses, snow manipulation treatments over one winter had limited influence on microbial community structure, bacterial or fungal copy numbers or enzyme activities. However, microbial community structure and activities shifted seasonally among soils sampled before snow melt, in early and late growing season and seemed driven by substrate availability. Bacterial and fungal communities were dominated by stress-resistant taxa such as the orders Acidobacteriales, Chaetothyriales and Helotiales that are likely adapted to adverse winter conditions. This study indicated that microbial communities in acidic northern boreal forest soil may be insensitive to direct effects of changing snow cover. However, in long term, the detrimental effects of increased ice and frost to plant roots may alter plant derived carbon and nutrient pools to the soil likely leading to stronger microbial responses.}, } @article {pmid29939126, year = {2018}, author = {Cho, HY and Heo, J and Hong, SB and Kim, JS and Kwon, SW and Kim, SJ}, title = {Simplicispira suum sp. nov., isolated from a dust collector at a pig farm.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2557-2561}, doi = {10.1099/ijsem.0.002874}, pmid = {29939126}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Comamonadaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; *Dust ; *Farms ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Swine ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative, strictly aerobic, polar-flagellated and rod-shaped bacterium, designated SC1-8T, was isolated from a dust collector at a pig farm located in Wanju-gun, Jeollabuk-do, Republic of Korea. The strain grew within a temperature range of 4-37 °C (optimum, 28-30 °C), at pH 7.0-9.0 (pH 7.0-8.0) and with 0-2 % (w/v) NaCl (0 %). Colonies were white-beige, circular and convex after 4 days of incubation on Reasoner's 2A agar. Based on the 16S rRNA gene sequence analysis, strain SC1-8T was a member of the genus Simplicispira, revealing the highest sequence similarities to Simplicispira limi EMB325T (97.9 %), Simplicispira psychrophila DSM 11588T (97.4 %), Acidovorax defluvii BSB411T (97.3 %), Simplicispira piscis RSG39T (97.1 %) and Simplicispira metamorpha DSM 1837T (97.0 %). The predominant respiratory quinone was Q-8. The polar lipids were phosphatidylethanolamone, diphosphatidylglycerol and phosphatidylglycerol. The major fatty acids (>10 % of the total fatty acids) were composed of C16 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The DNA G+C content was 63.3 mol%. On the basis of phenotypic, genotypic and phylogenetic evidence, strain SC1-8T is presented as a novel species, for which the name Simplicispira suum sp. nov. is proposed. The type strain is SC1-8T (=KACC 19329T=NBRC 113111T).}, } @article {pmid29939124, year = {2018}, author = {Fukano, H and Yoshida, M and Kazumi, Y and Fujiwara, N and Katayama, K and Ogura, Y and Hayashi, T and Miyamoto, Y and Fujimoto, N and Hongsheng, W and Mizumoto, C and Koizumi, Y and Maeda, H and Hiranuma, O and Mitarai, S and Ishii, N and Hoshino, Y}, title = {Mycobacterium shigaense sp. nov., a slow-growing, scotochromogenic species, is a member of the Mycobacterium simiae complex.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2437-2442}, doi = {10.1099/ijsem.0.002845}, pmid = {29939124}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Humans ; Japan ; Mycobacterium/*classification/genetics/isolation & purification ; Mycobacterium Infections/*microbiology ; Mycolic Acids/chemistry ; Nontuberculous Mycobacteria/classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin Diseases, Bacterial/*microbiology ; }, abstract = {Among non-tuberculous mycobacteria (NTM), the Mycobacterium simiae complex is one of the largest groups, consisting of 18 species of slow-growing mycobacteria. In 2009, a case of NTM-associated infectious skin disease was reported in Shiga Prefecture, Japan. The patient presented with scattered nodules on the chest, back and extremities, and an M. simiae-like organism was isolated from skin biopsy specimens obtained from one of these lesions. Based on several assessments, including multiple-gene analyses, biochemical characterization and drug susceptibility testing, we concluded that this isolate represented a novel species of NTM, and proposed the name 'Mycobacterium shigaense'. Since 2009, five more cases of NTM-associated infectious disease in which there was a suspected involvement of 'M. shigaense' have been reported. Interestingly, four of these six cases occurred in Shiga Prefecture. Here we performed multiple-gene phylogenetic analyses, physiological and biochemical characterization tests, drug susceptibility tests, and profiling of proteins, fatty acids and mycolic acids of eight clinical isolates from the six suspected 'M. shigaense' cases. The results confirmed that all of the clinical isolates were 'M. shigaense', a slow-growing, scotochromogenic species. Here M. shigaense is validly proposed as a new member of the M. simiae complex, with the type strain being UN-152T (=JCM 32072T=DSM 46748T).}, } @article {pmid29939122, year = {2018}, author = {Margesin, R and Albuquerque, L and Zhang, DC and Froufe, HJC and Severino, R and Roxo, I and Egas, C and da Costa, MS}, title = {Solimicrobium silvestre gen. nov., sp. nov., isolated from alpine forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2491-2498}, doi = {10.1099/ijsem.0.002861}, pmid = {29939122}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Italy ; Oxalobacteraceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, motile, catalase and cytochrome c oxidase-positive bacterial strain, designated S20-91T, was isolated from alpine forest soil. Growth occurred within a temperature range of 0-25 °C. Yeast extract was required for growth. Phylogenetic analysis based on 16S rRNA gene sequencing showed that strain S20-91T was related to the genus Herminiimonas and had the highest 16S rRNA gene sequence similarity to Herminiimonas arsenicoxydans ULPAs1T (96.5 %). The strain contained ubiquinone 8 as the predominant respiratory quinone and phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol as the major polar lipids. The major cellular fatty acids (>10 %) were C16 : 1ω7c (55.3 %) and C16 : 0 (25.6 %). The genomic DNA G+C content was 47.6 mol%. Combined data of genomic, phylogenetic, phenotypic and chemotaxonomic analyses demonstrated that strain S20-91T represents a novel genus and species, for which the name Solimicrobium silvestre gen. nov., sp. nov. is proposed. The type strain is S20-91T (=DSM 104733T=LMG 30010).}, } @article {pmid29939121, year = {2018}, author = {Cao, C and Sun, Y and Wu, B and Zhao, S and Yuan, B and Qin, S and Jiang, J and Huang, Y}, title = {Actinophytocola glycyrrhizae sp. nov. isolated from the rhizosphere of Glycyrrhiza inflata.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2504-2508}, doi = {10.1099/ijsem.0.002864}, pmid = {29939121}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycyrrhiza/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, aerobic actinomycete, designated strain BMP B8152T, was isolated from the rhizosphere of Glycyrrhiza inflata collected ashore, in Kashi, Xinjiang province, northwest PR China. A polyphasic approach was used to establish the taxonomic position of this strain. BMP B8152T was observed to form non-fragmented substrate mycelium, and relatively scanty aerial mycelium with rod-shaped spores. Cell-wall hydrolysates contained meso-diaminopimelic acid, galactose, arabinose, glucose and rhamnose (trace). Mycolic acids were not detected. The diagnostic phospholipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, ninhydrin-positive phosphoglycolipid and phosphatidylinositol. The predominant menaquinone and fatty acid were MK-9(H4) and iso-branched hexadecanoate (iso-C16 : 0), respectively. The phylogenetic analyses based on the 16S rRNA gene sequences indicated that BMP B8152T formed a distinct monophyletic clade clustered with Actinophytocola timorensisID05-A0653T (98.8 % 16S rRNA gene sequence similarity), Actinophytocola oryzaeGMKU 367T (98.6 %), Actinophytocola corallinaID06-A0464T (98.2 %) and Actinophytocola burenkhanensisMN08-A0203T (97.5 %). In addition, DNA-DNA hybridization values between BMP B8152T and A. timorensisID05-A0653T(44.2±3.6 %) and A. oryzaeGMKU 367T(36.7±2.3 %) were well below the 70 % limit for species identification. The combined phenotypic and genotypic data indicate that the isolate represents a novel species of the genus Actinophytocola, for which the name Actinophytocola glycyrrhizae sp. nov., is proposed, with the type strain BMP B8152T (=KCTC 49002T=CGMCC 4.7433T).}, } @article {pmid29939120, year = {2018}, author = {Hahn, MW and Koll, U and Schmidt, J and Huymann, LR and Karbon, G and Lang, E}, title = {Polynucleobacter hirudinilacicola sp. nov. and Polynucleobacter campilacus sp. nov., both isolated from freshwater systems.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2593-2601}, pmid = {29939120}, issn = {1466-5034}, support = {P 27160//Austrian Science Fund FWF/Austria ; }, mesh = {Austria ; Bacterial Typing Techniques ; Base Composition ; Burkholderiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/*microbiology ; Germany ; Lakes/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Strains MWH-EgelM1-30-B4T and MWH-Feld-100T were isolated from the water columns of two freshwater systems. Both strains represent delicate bacteria not easy to work with in laboratory experiments. Phylogenetic analyses of the 16S rRNA genes suggested that both strains were affiliated with the genus Polynucleobacter. Both strains share 16S rRNA gene sequence similarities of >99 % with eight free-living Polynucleobacter type strains, all affiliated with the cryptic species complex PnecC. The full-length 16S rRNA gene sequences of the two strains differ only in two and three positions, respectively, from the sequence of the closest related Polynucleobacter type strain. Genome sequencing of both strains revealed relatively small genome sizes of 2.0 Mbp and G+C contents of 45 mol%. Phylogenetic analyses based on nucleotide sequences of 319 shared protein-encoding genes consistently placed the two strains in taxon PnecC but did not suggest an affiliation with one of the previously described species. Pairwise analyses of whole genome average nucleotide identities (gANI) with representatives of all previously described Polynucleobacter species resulted in both cases throughout in values <80 %. Pairwise comparison of the genomes of the two new strains resulted in gANI values of 83.3 %. All gANI analyses clearly suggested that strains MWH-EgelM1-30-B4T and MWH-Feld-100T represent two novel Polynucleobacter species. We propose for these novel species the names Polynucleobacter hirudinilacicola sp. nov. and Polynucleobacter campilacus sp. nov. and strains MWH-EgelM1-30-B4T (=DSM 23911T=LMG 30144T) and MWH-Feld-100T (=DSM 24007T=LMG 29705T) as the type strains, respectively.}, } @article {pmid29938863, year = {2018}, author = {McDonald, TK and Yeaman, S}, title = {Effect of migration and environmental heterogeneity on the maintenance of quantitative genetic variation: a simulation study.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1386-1399}, doi = {10.1111/jeb.13341}, pmid = {29938863}, issn = {1420-9101}, support = {//AIHS/ ; }, abstract = {The paradox of high genetic variation observed in traits under stabilizing selection is a long-standing problem in evolutionary theory, as mutation rates appear too low to explain observed levels of standing genetic variation under classic models of mutation-selection balance. Spatially or temporally heterogeneous environments can maintain more standing genetic variation within populations than homogeneous environments, but it is unclear whether such conditions can resolve the above discrepancy between theory and observation. Here, we use individual-based simulations to explore the effect of various types of environmental heterogeneity on the maintenance of genetic variation (VA) for a quantitative trait under stabilizing selection. We find that VA is maximized at intermediate migration rates in spatially heterogeneous environments and that the observed patterns are robust to changes in population size. Spatial environmental heterogeneity increased variation by as much as 10-fold over mutation-selection balance alone, whereas pure temporal environmental heterogeneity increased variance by only 45% at max. Our results show that some combinations of spatial heterogeneity and migration can maintain considerably more variation than mutation-selection balance, potentially reconciling the discrepancy between theoretical predictions and empirical observations. However, given the narrow regions of parameter space required for this effect, this is unlikely to provide a general explanation for the maintenance of variation. Nonetheless, our results suggest that habitat fragmentation may affect the maintenance of VA and thereby reduce the adaptive capacity of populations.}, } @article {pmid29938105, year = {2018}, author = {Li, L and Zhang, Y and Liu, L and Wu, J and Li, S and Zhang, H and Zhang, B and Ding, M and Wang, Z and Paudel, B}, title = {Current challenges in distinguishing climatic and anthropogenic contributions to alpine grassland variation on the Tibetan Plateau.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5949-5963}, pmid = {29938105}, issn = {2045-7758}, abstract = {Quantifying the impact of climate change and human activities on grassland dynamics is an essential step for developing sustainable grassland ecosystem management strategies. However, the direction and magnitude of climate change and human activities in driving alpine grassland dynamic over the Tibetan Plateau remain under debates. Here, we systematically reviewed the relevant studies on the methods, main conclusions, and causes for the inconsistency in distinguishing the respective contribution of climatic and anthropogenic forces to alpine grassland dynamic. Both manipulative experiments and traditional statistical analysis show that climate warming increase biomass in alpine meadows and decrease in alpine steppes, while both alpine steppes and meadows benefit from an increase in precipitation or soil moisture. Overgrazing is a major factor for the degradation of alpine grassland in local areas with high level of human activity intensity. However, across the entire Tibetan Plateau and its subregions, four views characterize the remaining controversies: alpine grassland changes are primarily due to (1) climatic force, (2) nonclimatic force, (3) combination of anthropogenic and climatic force, or (4) alternation of anthropogenic and climatic force. Furthermore, these views also show spatial inconsistencies. Differences on the source and quality of remote sensing products, the structure and parameter of models, and overlooking the spatiotemporal heterogeneity of human activity intensity contribute to current disagreements. In this review, we highlight the necessity for taking the spatiotemporal heterogeneity of human activity intensity into account in the models of attribution assessment, and the importance for accurate validation of climatic and anthropogenic contribution to alpine grassland variation at multiple scales for future studies.}, } @article {pmid29938104, year = {2018}, author = {Parkins, K and York, A and Di Stefano, J}, title = {Edge effects in fire-prone landscapes: Ecological importance and implications for fauna.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5937-5948}, pmid = {29938104}, issn = {2045-7758}, abstract = {Edges are ecologically important environmental features and have been well researched in agricultural and urban landscapes. However, little work has been conducted in flammable ecosystems where spatially and temporally dynamic fire edges are expected to influence important processes such as recolonization of burnt areas and landscape connectivity. We review the literature on fire, fauna, and edge effects to summarize current knowledge of faunal responses to fire edges and identify knowledge gaps. We then develop a conceptual model to predict faunal responses to fire edges and present an agenda for future research. Faunal abundance at fire edges changes over time, but patterns depend on species traits and resource availability. Responses are also influenced by edge architecture (e.g., size and shape), site and landscape context, and spatial scale. However, data are limited and the influence of fire edges on both local abundance and regional distributions of fauna is largely unknown. In our conceptual model, biophysical properties interact with the fire regime (e.g., patchiness, frequency) to influence edge architecture. Edge architecture and species traits influence edge permeability, which is linked to important processes such as movement, resource selection, and species interactions. Predicting the effect of fire edges on fauna is challenging, but important for biodiversity conservation in flammable landscapes. Our conceptual model combines several drivers of faunal fire responses (biophysical properties, regime attributes, species traits) and will therefore lead to improved predictions. Future research is needed to understand fire as an agent of edge creation; the spatio-temporal flux of fire edges across landscapes; and the effect of fire edges on faunal movement, resource selection, and biotic interactions. To aid the incorporation of new data into our predictive framework, our model has been designed as a Bayesian Network, a statistical tool capable of analyzing complex environmental relationships, dealing with data gaps, and generating testable hypotheses.}, } @article {pmid29938103, year = {2018}, author = {Bendik, NF and Dries, LA}, title = {Density-dependent and density-independent drivers of population change in Barton Springs salamanders.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5912-5923}, pmid = {29938103}, issn = {2045-7758}, abstract = {Understanding population change is essential for conservation of imperiled species, such as amphibians. Worldwide amphibian declines have provided an impetus for investigating their population dynamics, which can involve both extrinsic (density-independent) and intrinsic (density-dependent) drivers acting differentially across multiple life stages or age classes. In this study, we examined the population dynamics of the endangered Barton Springs Salamander (Eurycea sosorum) using data from a long-term monitoring program. We were interested in understanding both the potential environmental drivers (density-independent factors) and demographic factors (interactions among size classes, negative density dependence) to better inform conservation and management activities. We used data from three different monitoring regimes and multivariate autoregressive state-space models to quantify environmental effects (seasonality, discharge, algae, and sediment cover), intraspecific interactions among three size classes, and intra-class density dependence. Results from our primary data set revealed similar patterns among sites and size classes and were corroborated by our out-of-sample data. Cross-correlation analysis showed juvenile abundance was most strongly correlated with a 9-month lag in aquifer discharge, which we suspect is related to inputs of organic carbon into the aquifer. However, sedimentation limited juvenile abundance at the surface, emphasizing the importance of continued sediment management. Recruitment from juveniles to the sub-adult size class was evident, but negative density-dependent feedback ultimately regulated each size class. Negative density dependence may be an encouraging sign for the conservation of E. sosorum because populations that can reach carrying capacity are less likely to go extinct compared to unregulated populations far below their carrying capacity. However, periodic population declines coupled with apparent migration into the aquifer complicate assessments of species status. Although both density-dependent and density-independent drivers of population change are not always apparent in time series of animal populations, both have important implications for conservation and management of E. sosorum.}, } @article {pmid29938102, year = {2018}, author = {Lai, M and He, S and Yu, S and Jin, G}, title = {Effects of experimental N addition on plant diversity in an old-growth temperate forest.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5900-5911}, pmid = {29938102}, issn = {2045-7758}, abstract = {Temperate forest ecosystems have experienced mounting negative effects due to increasing levels of nitrogen (N) deposition. We examined the effects of experimental N addition on plant diversity in an old-growth temperate forest to test the following hypothesis: Long-term excessive N addition decreases plant diversity by affecting the growth of plants, which results from changes in the soil nutrient content and a decrease in the soil pH in temperate forests. Experimental N additions were administered at the following levels since 2008: control (0 kg N ha-1 year-1), low N (30 kg N ha-1 year-1), medium N (60 kg N ha-1 year-1), and high N (120 kg N ha-1 year-1). Additionally, plant diversity was studied from 2014 to 2016. The results showed that the experimental N additions had significant effects on plant diversity and soil properties in an old-growth temperate forest. The high-N treatment decreased the density, cover, and diversity of understory plants, and some herbs even appeared to undergo premature aging, whereas the species diversity of herbs and ferns in the low-N treatment plots showed a slight increasing tendency. This may have been because the old-growth temperate forest is an N-limited ecosystem, so the moderate N input did not show a large influence on plant diversity. However, the long-term high-N treatment ultimately reduced plant diversity by changing the soil nutrient contents, decreasing the pH values, and damaging plant growth. Our results suggested that the long-term excessive N addition negatively affected the forest ecosystem in an N-limited temperature forest.}, } @article {pmid29938101, year = {2018}, author = {Huang, H and Zhang, H and Chen, C and Tang, L}, title = {Three-dimensional digitization of the arid land plant Haloxylon ammodendron using a consumer-grade camera.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5891-5899}, doi = {10.1002/ece3.4126}, pmid = {29938101}, issn = {2045-7758}, abstract = {Plant structural parameters are important for ecological studies and for monitoring the environment. Terrestrial laser scanning has become a widely accepted technique for acquiring accurate high-density three-dimensional information about plant surfaces; however, this instrument is expensive, technically challenging to operate, heavy, and difficult to transport to hard-to-reach areas such as dense forests and undeveloped areas without easy vehicle access. Using Haloxylon ammodendron, a plant widely distributed in arid lands, as an example, we used a consumer-grade handheld camera to take a series of overlapping images of this plant. Computer vision and photogrammetric software were used to reconstruct highly detailed three-dimensional data of the plant surface. This surface data was compared to the point cloud of the plant acquired from concomitant terrestrial laser scanning. We demonstrated that the accuracy and degree of completeness of the image-derived point clouds are comparable to that of laser scanning. Plant structural parameters (such as tree height and crown width) and three-dimensional models extracted from the point clouds also agree well with a relative difference of less than 5%. Our case study shows that a common camera and image processing software can be an affordable, highly portable, and viable option for acquiring accurate and detailed high-density and high-resolution three-dimensional information about plant structure in the environment. This digitization technique can record the plant and its surrounding environment effectively and efficiently, and it can be applied to many ecological fields and studies.}, } @article {pmid29938100, year = {2018}, author = {Klimova, A and Ortega-Rubio, A and Vendrami, DLJ and Hoffman, JI}, title = {Genotyping by sequencing reveals contrasting patterns of population structure, ecologically mediated divergence, and long-distance dispersal in North American palms.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5873-5890}, pmid = {29938100}, issn = {2045-7758}, abstract = {Comparative studies can provide powerful insights into processes that affect population divergence and thereby help to elucidate the mechanisms by which contemporary populations may respond to environmental change. Furthermore, approaches such as genotyping by sequencing (GBS) provide unprecedented power for resolving genetic differences among species and populations. We therefore used GBS to provide a genomewide perspective on the comparative population structure of two palm genera, Washingtonia and Brahea, on the Baja California peninsula, a region of high landscape and ecological complexity. First, we used phylogenetic analysis to address taxonomic uncertainties among five currently recognized species. We resolved three main clades, the first corresponding to W. robusta and W. filifera, the second to B. brandegeei and B. armata, and the third to B. edulis from Guadalupe Island. Focusing on the first two clades, we then delved deeper by investigating the underlying population structure. Striking differences were found, with GBS uncovering four distinct Washingtonia populations and identifying a suite of loci associated with temperature, consistent with ecologically mediated divergence. By contrast, individual mountain ranges could be resolved in Brahea and few loci were associated with environmental variables, implying a more prominent role of neutral divergence. Finally, evidence was found for long-distance dispersal events in Washingtonia but not Brahea, in line with knowledge of the dispersal mechanisms of these palms including the possibility of human-mediated dispersal. Overall, our study demonstrates the power of GBS together with a comparative approach to elucidate markedly different patterns of genomewide divergence mediated by multiple effectors.}, } @article {pmid29938099, year = {2018}, author = {Viejou, R and Avgar, T and Brown, GS and Patterson, BR and Reid, DEB and Rodgers, AR and Shuter, J and Thompson, ID and Fryxell, JM}, title = {Woodland caribou habitat selection patterns in relation to predation risk and forage abundance depend on reproductive state.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5863-5872}, pmid = {29938099}, issn = {2045-7758}, abstract = {The ideal free distribution assumes that animals select habitats that are beneficial to their fitness. When the needs of dependent offspring differ from those of the parent, ideal habitat selection patterns could vary with the presence or absence of offspring. We test whether habitat selection depends on reproductive state due to top-down or bottom-up influences on the fitness of woodland caribou (Rangifer tarandus caribou), a threatened, wide-ranging herbivore. We combined established methods of fitting resource and step selection functions derived from locations of collared animals in Ontario with newer techniques, including identifying calf status from video collar footage and seasonal habitat selection analysis through latent selection difference functions. We found that females with calves avoided predation risk and proximity to roads more strongly than females without calves within their seasonal ranges. At the local scale, females with calves avoided predation more strongly than females without calves. Females with calves increased predation avoidance but not selection for food availability upon calving, whereas females without calves increased selection for food availability across the same season. These behavioral responses suggest that habitat selection by woodland caribou is influenced by reproductive state, such that females with calves at heel use habitat selection to offset the increased vulnerability of their offspring to predation risk.}, } @article {pmid29938098, year = {2018}, author = {Gall, BG and Spivey, KL and Chapman, TL and Delph, RJ and Brodie, ED and Wilson, JS}, title = {The indestructible insect: Velvet ants from across the United States avoid predation by representatives from all major tetrapod clades.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5852-5862}, pmid = {29938098}, issn = {2045-7758}, abstract = {Velvet ants are a group of parasitic wasps that are well known for a suite of defensive adaptations including bright coloration and a formidable sting. While these adaptations are presumed to function in antipredator defense, observations between potential predators and this group are lacking. We conducted a series of experiments to determine the risk of velvet ants to a host of potential predators including amphibians, reptiles, birds, and small mammals. Velvet ants from across the United States were tested with predator's representative of the velvet ants native range. All interactions between lizards, free-ranging birds, and a mole resulted in the velvet ants survival, and ultimate avoidance by the predator. Two shrews did injure a velvet ant, but this occurred only after multiple failed attacks. The only predator to successfully consume a velvet ant was a single American toad (Anaxyrus americanus). These results indicate that the suite of defenses possessed by velvet ants, including aposematic coloration, stridulations, a chemical alarm signal, a hard exoskeleton, and powerful sting are effective defenses against potential predators. Female velvet ants appear to be nearly impervious to predation by many species whose diet is heavily derived of invertebrate prey.}, } @article {pmid29938097, year = {2018}, author = {Fitzek, E and Delcamp, A and Guichoux, E and Hahn, M and Lobdell, M and Hipp, AL}, title = {A nuclear DNA barcode for eastern North American oaks and application to a study of hybridization in an Arboretum setting.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5837-5851}, pmid = {29938097}, issn = {2045-7758}, abstract = {DNA barcoding has proved difficult in a number of woody plant genera, including the ecologically important oak genus Quercus. In this study, we utilized restrictionsite-associated DNA sequencing (RAD-seq) to develop an economical single nucleotide polymorphism (SNP) DNA barcoding system that suffices to distinguish eight common, sympatric eastern North American white oak species. Two de novo clustering pipelines, PyRAD and Stacks, were used in combination with postclustering bioinformatic tools to generate a list of 291 potential SNPs, 80 of which were included in a barcoding toolkit that is easily implemented using MassARRAY mass spectrometry technology. As a proof-of-concept, we used the genotyping toolkit to infer potential hybridization between North American white oaks transplanted outside of their native range (Q. michauxii, Q. montana, Q muehlenbergii/Q. prinoides, and Q. stellata) into a horticultural collection surrounded by natural forests of locally native trees (Q. alba and Q. macrocarpa) in the living collection at The Morton Arboretum (Lisle, IL, USA). Phylogenetic and clustering analyses suggested low rates of hybridization between cultivated and native species, with the exception of one Q. michauxii mother tree, the acorns of which exhibited high admixture from either Q. alba or Q. stellata and Q. macrocarpa, and a hybrid between Q. stellata that appears to have backcrossed almost exclusively to Q. alba. Together, RAD-seq and MassARRAY technologies allow for efficient development and implementation of a multispecies barcode for one of the more challenging forest tree genera.}, } @article {pmid29938096, year = {2018}, author = {Muniz, DG and Baena, ML and Macías-Ordóñez, R and Machado, G}, title = {Males, but not females, perform strategic mate searching movements between host plants in a leaf beetle with scramble competition polygyny.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5828-5836}, pmid = {29938096}, issn = {2045-7758}, abstract = {Mate searching is assumed to be performed mostly by males, but when females benefit from multiple mating or are under risk of failing to mate, they may also perform mate searching. This is especially important in scramble competition polygynies, in which mate searching is the main mechanism of mate competition. Typically, more mobile individuals are expected to achieve higher mating success because mobility increases their probability of finding mates. If we assume individual movements are mainly explained by mate searching in scramble competition polygynies, we can investigate searching strategies by asking when individuals should leave their location and where they should go. We hypothesize that individuals will leave their locations when mating opportunities are scarce and will seek spatially close sites with better mating opportunities. We tested these hypotheses for males and females of Leptinotarsa undecimlineata, a leaf beetle with scramble competition polygyny in which both sexes are promiscuous. Individuals mate and feed exclusively on Solanum plants, and thus, individual movements can be described as switches between plants. Females were less likely than males to leave isolated plants, and both males and females moved preferentially to neighboring plants. Males were more likely to leave when the local number of females was low, and the number of males was high. They moved to plants with more females, a behavior consistent with a mate searching strategy. Females were more likely to move to plants with fewer males and many females, a behavior consistent with male harassment avoidance. Strategic movement is widely considered in foraging context, but seldom in a mate searching context. Considering that selection to minimize searching costs, maximize mating success, and minimize harassment may be ubiquitous in nature, we argue that strategic movements by mate searching individuals are likely to occur in many species.}, } @article {pmid29938095, year = {2018}, author = {Janzen, FJ and Hoekstra, LA and Brooks, RJ and Carroll, DM and Gibbons, JW and Greene, JL and Iverson, JB and Litzgus, JD and Michael, ED and Parren, SG and Roosenburg, WM and Strain, GF and Tucker, JK and Ultsch, GR}, title = {Altered spring phenology of North American freshwater turtles and the importance of representative populations.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5815-5827}, pmid = {29938095}, issn = {2045-7758}, abstract = {Globally, populations of diverse taxa have altered phenology in response to climate change. However, most research has focused on a single population of a given taxon, which may be unrepresentative for comparative analyses, and few long-term studies of phenology in ectothermic amniotes have been published. We test for climate-altered phenology using long-term studies (10-36 years) of nesting behavior in 14 populations representing six genera of freshwater turtles (Chelydra, Chrysemys, Kinosternon, Malaclemys, Sternotherus, and Trachemys). Nesting season initiation occurs earlier in more recent years, with 11 of the populations advancing phenology. The onset of nesting for nearly all populations correlated well with temperatures during the month preceding nesting. Still, certain populations of some species have not advanced phenology as might be expected from global patterns of climate change. This collection of findings suggests a proximate link between local climate and reproduction that is potentially caused by variation in spring emergence from hibernation, ability to process food, and thermoregulatory opportunities prior to nesting. However, even though all species had populations with at least some evidence of phenological advancement, geographic variation in phenology within and among turtle species underscores the critical importance of representative data for accurate comprehensive assessments of the biotic impacts of climate change.}, } @article {pmid29938094, year = {2018}, author = {Amorim, F and Jorge, I and Beja, P and Rebelo, H}, title = {Following the water? Landscape-scale temporal changes in bat spatial distribution in relation to Mediterranean summer drought.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5801-5814}, pmid = {29938094}, issn = {2045-7758}, abstract = {Understanding how the spatial distribution of ecological resources shapes species' diversity and abundance in human-modified landscapes is a central theme in conservation biology. However, studies often disregard that such patterns may vary over time, thereby potentially missing critical environmental constraints to species persistence. This may be particularly important in highly mobile species such as bats, which are able to track temporal variations in spatial resource distribution. Here we test the hypothesis that bats in Mediterranean landscapes are strongly affected by the progressive reduction in water availability during the seasonal summer drought. We analyzed the effects of landscape composition and structure on bat diversity and activity, during pregnancy, lactation, and postlactation periods, and identified the most influential variables within and across periods. Water bodies showed the strongest positive effect on bats, followed by riparian habitats and areas with steeper (>30%) slopes. However, while during pregnancy, there were only small landscape effects, these increased during lactation and postlactation, highlighting a progressively stronger association with water habitats during the summer drought. The spatial projection of habitat models showed that the landscape distribution of bat diversity and activity hotspots changed markedly over time. During pregnancy, the spatial pattern of hotspot distribution was weakly defined, while during lactation and particularly postlactation, there was a concentration of hotspots along permanently flowing watercourses. Our study highlights that permanently flowing watercourses are critical for bat conservation in Mediterranean landscapes, calling for measures to counteract their ongoing degradation due in particular to climate change, water abstraction and damming. More generally, our study underlines the importance of considering the temporal dimension in habitat selection studies, without which there is the risk of overlooking the importance of habitats that are key for species persistence only at certain times of the year.}, } @article {pmid29938093, year = {2018}, author = {Christian, N and Bever, JD}, title = {Carbon allocation and competition maintain variation in plant root mutualisms.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5792-5800}, pmid = {29938093}, issn = {2045-7758}, abstract = {Plants engage in multiple root symbioses that offer varying degrees of benefit. We asked how variation in partner quality persists using a resource-ratio model of population growth. We considered the plant's ability to preferentially allocate carbon to mutualists and competition for plant carbon between mutualist and nonmutualist symbionts. We treated carbon as two nutritionally interchangeable, but temporally separated, resources-carbon allocated indiscriminately for the construction of the symbiosis, and carbon preferentially allocated to the mutualist after symbiosis establishment and assessment. This approach demonstrated that coexistence of mutualists and nonmutualists is possible when fidelity of the plant to the mutualist and the cost of mutualism mediate resource competition. Furthermore, it allowed us to trace symbiont population dynamics given varying degrees of carbon allocation. Specifically, coexistence occurs at intermediate levels of preferential allocation. Our findings are consistent with previous empirical studies as well the application of biological market theory to plantroot symbioses.}, } @article {pmid29938092, year = {2018}, author = {Persson, AS and Mazier, F and Smith, HG}, title = {When beggars are choosers-How nesting of a solitary bee is affected by temporal dynamics of pollen plants in the landscape.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5777-5791}, pmid = {29938092}, issn = {2045-7758}, abstract = {Wild bees are declining in intensively farmed regions worldwide, threatening pollination services to flowering crops and wild plants. To halt bee declines, it is essential that conservation actions are based on a mechanistic understanding of how bee species utilize landscapes. We aimed at teasing apart how foraging resources in the landscape through the nesting season affected nesting and reproduction of a solitary bee in a farmland region. We investigated how availability of floral resources and potentially resource-rich habitats surrounding nests affected nest provisioning and reproduction in the solitary polylectic bee Osmia bicornis. The study was performed in 18 landscape sectors dominated by agriculture, but varying in agricultural intensity in terms of proportion of organic crop fields and seminatural permanent pastures. Pasture-rich sectors contained more oak (Quercus robur), which pollen analysis showed to be favored forage in early season. More oaks ≤100 m from nests led to higher proportions of oak pollen in nest provisions and increased speed of nest construction in early season, but this effect tapered off as flowering decreased. Late-season pollen foraging was dominated by buttercup (Ranunculus spp.), common in various noncrop habitats. Foraging trips were longer with more oaks and increased further through the season. The opposite was found for buttercup. Oak and buttercup interacted to explain the number of offspring; buttercup had a positive effect only when the number of oaks was above the mean for the studied sectors. The results show that quality of complex and pasture-rich landscapes for O. bicornis depends on preserving existing and generating new oak trees. Lignose plants are key early-season forage resources in agricultural landscapes. Increasing habitat heterogeneity with trees and shrubs and promoting suitable late-flowering forbs can benefit O. bicornis and other wild bees active in spring and early summer, something which existing agri-environment schemes seldom target.}, } @article {pmid29938091, year = {2018}, author = {Vaudo, AD and Farrell, LM and Patch, HM and Grozinger, CM and Tooker, JF}, title = {Consistent pollen nutritional intake drives bumble bee (Bombus impatiens) colony growth and reproduction across different habitats.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5765-5776}, pmid = {29938091}, issn = {2045-7758}, abstract = {Foraging behavior is a critical adaptation by insects to obtain appropriate nutrients from the environment for development and fitness. Bumble bees (Bombus spp.) form annual colonies which must rapidly increase their worker populations to support rearing reproductive individuals before the end of the season. Therefore, colony growth and reproduction should be dependent on the quality and quantity of pollen resources in the surrounding landscape. Our previous research found that B. impatiens foraging preferences to different plant species were shaped by pollen protein:lipid nutritional ratios (P:L), with foragers preferring pollen species with a ~5:1 P:L ratio. In this study, we placed B. impatiens colonies in three different habitats (forest, forest edge, and valley) to determine whether pollen nutritional quality collected by the colonies differed between areas that may differ in resource abundance and diversity. We found that habitat did not influence the collected pollen nutritional quality, with colonies in all three habitats collecting pollen averaging a 4:1 P:L ratio. Furthermore, there was no difference in the nutritional quality of the pollen collected by colonies that successfully reared reproductives and those that did not. We found however, that "nutritional intake," calculated as the colony-level intake rate of nutrient quantities (protein, lipid, and sugar), was strongly related to colony growth and reproductive output. Therefore, we conclude that B. impatiens colony performance is a function of the abundance of nutritionally appropriate floral resources in the surrounding landscape. Because we did not comprehensively evaluate the nutrition provided by the plant communities in each habitat, it remains to be determined how B. impatiens polylectic foraging strategies helps them select among the available pollen nutritional landscape in a variety of plant communities to obtain a balance of key macronutrients.}, } @article {pmid29938090, year = {2018}, author = {Reczuga, MK and Lamentowicz, M and Mulot, M and Mitchell, EAD and Buttler, A and Chojnicki, B and Słowiński, M and Binet, P and Chiapusio, G and Gilbert, D and Słowińska, S and Jassey, VEJ}, title = {Predator-prey mass ratio drives microbial activity under dry conditions in Sphagnum peatlands.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5752-5764}, pmid = {29938090}, issn = {2045-7758}, abstract = {Mid- to high-latitude peatlands are a major terrestrial carbon stock but become carbon sources during droughts, which are increasingly frequent as a result of climate warming. A critical question within this context is the sensitivity to drought of peatland microbial food webs. Microbiota drive key ecological and biogeochemical processes, but their response to drought is likely to impact these processes. Peatland food webs have, however, been little studied, especially the response of microbial predators. We studied the response of microbial predators (testate amoebae, ciliates, rotifers, and nematodes) living in Sphagnum moss carpet to droughts, and their influence on lower trophic levels and on related microbial enzyme activity. We assessed the impact of reduced water availability on microbial predators in two peatlands using experimental (Linje mire, Poland) and natural (Forbonnet mire, France) water level gradients, reflecting a sudden change in moisture regime (Linje), and a typically drier environment (Forbonnet). The sensitivity of different microbial groups to drought was size dependent; large sized microbiota such as testate amoebae declined most under dry conditions (-41% in Forbonnet and -80% in Linje). These shifts caused a decrease in the predator-prey mass ratio (PPMR). We related microbial enzymatic activity to PPMR; we found that a decrease in PPMR can have divergent effects on microbial enzymatic activity. In a community adapted to drier conditions, decreasing PPMR stimulated microbial enzyme activity, while in extreme drought experiment, it reduced microbial activity. These results suggest that microbial enzymatic activity resulting from food web structure is optimal only within a certain range of PPMR, and that different trophic mechanisms are involved in the response of peatlands to droughts. Our findings confirm the importance of large microbial consumers living at the surface of peatlands on the functioning of peatlands, and illustrate their value as early warning indicators of change.}, } @article {pmid29938089, year = {2018}, author = {Gallegos Sánchez, CF and Beltrán, J and Flores, V and González, AV and Santelices, B}, title = {Testing the effects of heterozygosity on growth rate plasticity in the seaweed Gracilaria chilensis (Rhodophyta).}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5741-5751}, pmid = {29938089}, issn = {2045-7758}, abstract = {Heterozygosity has been positively associated with fitness and population survival. However, the relationship between heterozygosity and adaptive phenotypic plasticity (i.e., plasticity which results in fitness homeostasis or improvement in changing environments) is unclear and has been poorly explored in seaweeds. In this study, we explored this relationship in the clonal red seaweed, Gracilaria chilensis by conducting three growth rate plasticity experiments under contrasting salinity conditions and by measuring heterozygosity with five microsatellite DNA markers. Firstly, we compared growth rate plasticity between the haploid and diploid phases. Secondly, we compared growth rate plasticity between diploids with different numbers of heterozygous loci. Finally, we compared growth rate plasticity between diploid plants from two populations that are expected to exhibit significant differences in heterozygosity. We found that, (i) diploids displayed a higher growth rate and lower growth rate plasticity than haploids, (ii) diploids with a higher number of heterozygous loci displayed lower growth rate plasticity than those exhibiting less heterozygosity, and (iii) diploid sporophytes from the population with higher heterozygosity displayed lower growth rate plasticity than those with lower heterozygosity. Accordingly, this study suggests that heterozygosity is inversely related to growth rate plasticity in G. chilensis. However, better genetic tools in seaweeds are required for a more definitive conclusion on the relationship between heterozygosity and phenotypic plasticity.}, } @article {pmid29938088, year = {2018}, author = {Ahmad, H and Hayat, S and Ali, M and Liu, T and Cheng, Z}, title = {The combination of arbuscular mycorrhizal fungi inoculation (Glomus versiforme) and 28-homobrassinolide spraying intervals improves growth by enhancing photosynthesis, nutrient absorption, and antioxidant system in cucumber (Cucumis sativus L.) under salinity.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5724-5740}, pmid = {29938088}, issn = {2045-7758}, abstract = {Salinity is one of the major obstacles in the agriculture industry causing huge losses in productivity. Several strategies such as plant growth regulators with arbuscular mycorrhizal fungi (AMF) have been used to decrease the negative effects of salt stress. In our experiment, 28-homobrassinolide (HBL) with spraying intervals was combined with AMF (Glomus versiforme) in cucumber cultivars Jinyou 1# (salt sensitive) and (Changchun mici, in short, CCMC, salt tolerant) under NaCl (100 mmol/L). Studies have documented that the foliar application of HBL and AMF colonization can enhance tolerance to plants under stress conditions. However, the mechanism of the HBL spraying intervals after 15 and 30 days in combination with AMF in cucumber under salt stress is still unknown. Our results revealed that the HBL spraying interval after 15 days in combination with AMF resulted in improved growth, photosynthesis, and decreased sodium toxicity under NaCl. Moreover, the antioxidant enzymes SOD (superoxide dismutase; EC 1.15.1.1) and POD activity (peroxidase; EC 1.11.1.7) showed a gradual increase after every 10 days, while the CAT (catalase; EC 1.11.1.6) increased after 30 days of salt treatments in both cultivars. This research suggests that the enhanced tolerance to salinity was mainly related to elevated levels of antioxidant enzymes and lower uptake of Na+, which lowers the risk of ion toxicity and decreases cell membrane damage.}, } @article {pmid29938087, year = {2018}, author = {Garbin, ML and Misaki, F and Ferreira, PF and Guidoni-Martins, KG and Soares, RB and Mariotte, P and Sansevero, JBB and Rocha, PG and Silva, AG}, title = {Long-term regeneration of a tropical plant community after sand mining.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5712-5723}, pmid = {29938087}, issn = {2045-7758}, abstract = {Sandy coastal plant communities in tropical regions have been historically under strong anthropic pressure. In Brazil, these systems shelter communities with highly plastic plant species. However, the potential of these systems to regenerate without human assistance after disturbances has hardly been examined. We determined the natural regeneration of a coastal sandy plain vegetation (restinga) in Brazil, 16 years after the end of sand removal. We inventoried 38 plots: 20 within a sand-mined site and 18 in an adjacent undisturbed site. We expected lower diversity values in the sand-mined site compared to the undisturbed site, but similar species composition between the two sites due to the spatial proximity of the two sites and the high plasticity of restinga species. Species were ranked using abundance and importance value index in both sites, and comparisons were performed using Rényi entropy profiles, rarefaction curves, principal component analysis, and redundancy analysis. Species composition and dominant species differed markedly between the two sites. Bromeliads and Clusia hilariana, well-known nurse plants, dominated the undisturbed site but were almost absent in the regenerating site. Species richness did not differ between both sites, but diversity was higher in the undisturbed site. Within-site composition differences in the mined area were associated with field characteristics. Interestingly, species classified as subordinate or rare in the undisturbed site became dominants in the regenerating site. These newer dominants in the sand-mined site are not those known as nurse plants in other restingas, thus yielding strong implications for restoration.}, } @article {pmid29938086, year = {2018}, author = {Leišová-Svobodová, L and Phillips, J and Martinussen, I and Holubec, V}, title = {Genetic differentiation of Rubus chamaemorus populations in the Czech Republic and Norway after the last glacial period.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5701-5711}, pmid = {29938086}, issn = {2045-7758}, abstract = {The population structure of cloudberry (Rubus chamaemorus L.), collected from Krkonose Mountains (the Czech Republic), continental Norway and Spitsbergen, was examined using microsatellite analyses (SSR). Among 184 individuals, 162 different genotypes were identified. The overall unbiased gene diversity was high (h ^ = 0.463). A high level of genetic differentiation among populations (FST = 0.45; p < .01) indicated restricted gene flow between populations. Using a Bayesian approach, six clusters were found which represented the genetic structure of the studied cloudberry populations. The value of correlation index between genetic and geographical distances (r = .44) indicates that gene flow, even over a long distance, could exist. An exact test of population differentiation showed that Rubus chamaemorus populations from regions (Krkonose Mountains, continental Norway and Spitsbergen) are differentiated although some individuals within populations share common alleles even among regions. These results were confirmed by AMOVA, where the highest level of diversity was found within populations (70.8%). There was no difference between 87 pairs of populations (18.7%) mostly within cloudberry populations from continental Norway and from Spitsbergen. Based on obtained results, it is possible to conclude that Czech and Norwegian cloudberry populations are undergoing differentiation, which preserves unique allele compositions most likely from original populations during the last glaciation period. This knowledge will be important for the creation and continuation of in situ and ex situ conservation of cloudberry populations within these areas.}, } @article {pmid29938085, year = {2018}, author = {Bellard, C and Jeschke, JM and Leroy, B and Mace, GM}, title = {Insights from modeling studies on how climate change affects invasive alien species geography.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5688-5700}, pmid = {29938085}, issn = {2045-7758}, abstract = {Climate change and biological invasions are threatening biodiversity and ecosystem services worldwide. It has now been widely acknowledged that climate change will affect biological invasions. A large number of studies have investigated predicted shifts and other changes in the geographic ranges of invasive alien species related to climate change using modeling approaches. Yet these studies have provided contradictory evidence, and no consensus has been reached. We conducted a systematic review of 423 modeling case studies included in 71 publications that have examined the predicted effects of climate change on those species. We differentiate the approaches used in these studies and synthesize their main results. Our results reaffirm the major role of climate change as a driver of invasive alien species distribution in the future. We found biases in the literature both regarding the taxa, toward plants and invertebrates, and the areas of the planet investigated. Despite these biases, we found for the plants and vertebrates studied that climate change will more frequently contribute to a decrease in species range size than an increase in the overall area occupied. This is largely due to oceans preventing terrestrial invaders from spreading poleward. In contrast, we found that the ranges of invertebrates and pathogens studied are more likely to increase following climate change. An important caveat to these findings is that researchers have rarely considered the effects of climate change on transport, introduction success, or the resulting impacts. We recommend closing these research gaps, and propose additional avenues for future investigations, as well as opportunities and challenges for managing invasions under climate change.}, } @article {pmid29938084, year = {2018}, author = {Farnsworth, JM and Baasch, DM and Smith, C and Werbylo, KL}, title = {Reproductive ecology of interior least tern and piping plover in relation to Platte river hydrology and sandbar dynamics: Response to the letter to the editor.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5680-5687}, pmid = {29938084}, issn = {2045-7758}, abstract = {This is a response to the Alexander, Jorgensen, and Bomberger-Brown (Ecology and Evolution, XX, 2018, XX; hereafter, AJB) Letter to the Editor critiquing Farnsworth et al. (Ecology and Evolution, 7, 2017, 3579; hereafter, our study), which investigates the reproductive ecology of interior least terns and piping plover in relation to Platte River hydrology and sandbar dynamics. Herein, we address each of AJBs' technical arguments, demonstrating that our technical approach and model assumptions were reasonable and provide a conservatively high estimate of the potential for reproductive success when compared to observed nest inundation events. We conclude with a description of the realities faced by the Platte River Recovery Implementation Program (PRRIP) as we integrate learning to adjust management actions. Linked Article: https://doi.org/10.1002/ece3.4109.}, } @article {pmid29938083, year = {2018}, author = {Alexander, JS and Jorgensen, JG and Brown, MB}, title = {Reproductive ecology of interior least tern and piping plover in relation to Platte River hydrology and sandbar dynamics.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5674-5679}, pmid = {29938083}, issn = {2045-7758}, abstract = {In a recent study, Farnsworth et al. (2017) used distributions of nest initiation dates drawn mostly from human-created, off-channel habitats and a model of emergent sandbar habitat to evaluate the hypothesis that least terns (Sternula antillarum) and piping plovers (Charadrius melodus) are physiologically adapted to initiate nests concurrent with the cessation of spring river flow rises on two sections of the Platte River, Nebraska. The study by Farnsworth et al. (2017) has several shortcomings which bring into question the authors' principal assertion that interior least tern and piping plovers are not adapted to occupying and nesting on river sandbars on the Platte River system. We identify these shortcomings and provide information, which, we suggest, would change their conclusions if incorporated. Linked Article: https://doi.org/10.1002/ece3.4097.}, } @article {pmid29938082, year = {2018}, author = {Pérez-Alquicira, J and Weller, SG and Domínguez, CA and Molina-Freaner, FE and Tsyusko, OV}, title = {Different patterns of colonization of Oxalis alpina in the Sky Islands of the Sonoran desert via pollen and seed flow.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5661-5673}, pmid = {29938082}, issn = {2045-7758}, abstract = {Historical factors such as climatic oscillations during the Pleistocene epoch have dramatically impacted species distributions. Studies of the patterns of genetic structure in angiosperm species using molecular markers with different modes of inheritance contribute to a better understanding of potential differences in colonization and patterns of gene flow via pollen and seeds. These markers may also provide insights into the evolution of reproductive systems in plants. Oxalis alpina is a tetraploid, herbaceous species inhabiting the Sky Island region of the southwestern United States and northern Mexico. Our main objective in this study was to analyze the influence of climatic oscillations on the genetic structure of O. alpina and the impact of these oscillations on the evolutionary transition from tristylous to distylous reproductive systems. We used microsatellite markers and compared our results to a previous study using chloroplast genetic markers. The phylogeographic structure inferred by both markers was different, suggesting that intrinsic characteristics including the pollination system and seed dispersal have influenced patterns of gene flow. Microsatellites exhibited low genetic structure, showed no significant association between geographic and genetic distances, and all individual genotypes were assigned to two main groups. In contrast, chloroplast markers exhibited a strong association between geographic and genetic distance, had higher levels of genetic differentiation, and were assigned to five groups. Both types of DNA markers showed evidence of a northward expansion as a consequence of climate warming occurring in the last 10,000 years. The data from both types of markers support the hypothesis for several independent transitions from tristyly to distyly.}, } @article {pmid29938081, year = {2018}, author = {McGranahan, DA and Geaumont, B and Spiess, JW}, title = {Assessment of a livestock GPS collar based on an open-source datalogger informs best practices for logging intensity.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5649-5660}, pmid = {29938081}, issn = {2045-7758}, abstract = {Ecologists have used Global Positioning Systems (GPS) to track animals for 30 years. Issues today include logging frequency and precision in estimating space use and travel distances, as well as battery life and cost. We developed a low-cost (~US$125), open-source GPS datalogger based on Arduino. To test the system, we collected positions at 20-s intervals for several 1-week durations from cattle and sheep on rangeland in North Dakota. We tested two questions of broad interest to ecologists who use GPS collars to track animal movements: (1) How closely do collared animals cluster in their herd? (2) How well do different logging patterns estimate patch occupancy and total daily distance traveled? Tested logging patterns included regular logging (one position every 5 or 10 min), and burst logging (positions recorded at 20-s intervals for 5 or 10 min per hour followed by a sleep period). Collared sheep within the same pasture spent 75% of daytime periods within 51 m of each other (mean = 42 m); collared cattle were within 111 m (mean = 76 m). In our comparison of how well different logging patterns estimate space use versus constant logging, the proportion of positions recorded in 1- and 16-ha patches differed by 2%-3% for burst logging and 1% for regular logging. Although all logging patterns underestimated total daily distance traveled, underestimations were corrected by multiplying estimations by regression coefficients estimated by maximum likelihood. Burst logging can extend battery life by a factor of 7. We conclude that a minimum of two collars programmed with burst logging robustly estimate patch use and spatial distribution of grazing livestock herds. Research questions that require accurately estimating travel of individual animals, however, are probably best addressed with regular logging intervals and will thus have greater battery demands than spatial occupancy questions across all GPS datalogger systems.}, } @article {pmid29938080, year = {2018}, author = {Pauquet, G and Salzburger, W and Egger, B}, title = {The puzzling phylogeography of the haplochromine cichlid fish Astatotilapia burtoni.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5637-5648}, pmid = {29938080}, issn = {2045-7758}, abstract = {Astatotilapia burtoni is a member of the "modern haplochromines," the most species-rich lineage within the family of cichlid fishes. Although the species has been in use as research model in various fields of research since almost seven decades, including developmental biology, neurobiology, genetics and genomics, and behavioral biology, little is known about its spatial distribution and phylogeography. Here, we examine the population structure and phylogeographic history of A. burtoni throughout its entire distribution range in the Lake Tanganyika basin. In addition, we include several A. burtoni laboratory strains to trace back their origin from wild populations. To this end, we reconstruct phylogenetic relationships based on sequences of the mitochondrial DNA (mtDNA) control region (d-loop) as well as thousands of genomewide single nucleotide polymorphisms (SNPs) derived from restriction-associated DNA sequencing. Our analyses reveal high population structure and deep divergence among several lineages, however, with discordant nuclear and mtDNA phylogenetic inferences. Whereas the SNP-based phylogenetic hypothesis uncovers an unexpectedly deep split in A. burtoni, separating the populations in the southern part of the Lake Tanganyika basin from those in the northern part, analyses of the mtDNA control region suggest deep divergence between populations from the southwestern shoreline and populations from the northern and southeastern shorelines of Lake Tanganyika. This phylogeographic pattern and mitochondrial haplotype sharing between populations from the very North and the very South of Lake Tanganyika can only partly be explained by introgression linked to lake-level fluctuations leading to past contact zones between otherwise isolated populations and large-scale migration events.}, } @article {pmid29938079, year = {2018}, author = {Pais, AL and Li, X and Jenny Xiang, QY}, title = {Discovering variation of secondary metabolite diversity and its relationship with disease resistance in Cornus florida L.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5619-5636}, pmid = {29938079}, issn = {2045-7758}, abstract = {Understanding intraspecific relationships between genetic and functional diversity is a major goal in the field of evolutionary biology and is important for conserving biodiversity. Linking intraspecific molecular patterns of plants to ecological pressures and trait variation remains difficult due to environment-driven plasticity. Next-generation sequencing, untargeted liquid chromatography-mass spectrometry (LC-MS) profiling, and interdisciplinary approaches integrating population genomics, metabolomics, and community ecology permit novel strategies to tackle this problem. We analyzed six natural populations of the disease-threatened Cornus florida L. from distinct ecological regions using genotype-by-sequencing markers and LC-MS-based untargeted metabolite profiling. We tested the hypothesis that higher genetic diversity in C. florida yielded higher chemical diversity and less disease susceptibility (screening hypothesis), and we also determined whether genetically similar subpopulations were similar in chemical composition. Most importantly, we identified metabolites that were associated with candidate loci or were predictive biomarkers of healthy or diseased plants after controlling for environment. Subpopulation clustering patterns based on genetic or chemical distances were largely congruent. While differences in genetic diversity were small among subpopulations, we did observe notable similarities in patterns between subpopulation averages of rarefied-allelic and chemical richness. More specifically, we found that the most abundant compound of a correlated group of putative terpenoid glycosides and derivatives was correlated with tree health when considering chemodiversity. Random forest biomarker and genomewide association tests suggested that this putative iridoid glucoside and other closely associated chemical features were correlated to SNPs under selection.}, } @article {pmid29938078, year = {2018}, author = {Dalponte, M and Frizzera, L and Gianelle, D}, title = {How to map forest structure from aircraft, one tree at a time.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5611-5618}, pmid = {29938078}, issn = {2045-7758}, abstract = {Forest structure is strongly related to forest ecology, and it is a key parameter to understand ecosystem processes and services. Airborne laser scanning (ALS) is becoming an important tool in environmental mapping. It is increasingly common to collect ALS data at high enough point density to recognize individual tree crowns (ITCs) allowing analyses to move beyond classical stand-level approaches. In this study, an effective and simple method to map ITCs, and their stem diameter and aboveground biomass (AGB) is presented. ALS data were used to delineate ITCs and to extract ITCs' height and crown diameter; then, using newly developed allometries, the ITCs' diameter at breast height (DBH) and AGB were predicted. Gini coefficient of DBHs was also predicted and mapped aggregating ITCs predictions. Two datasets from spruce dominated temperate forests were considered: one was used to develop the allometric models, while the second was used to validate the methodology. The proposed approach provides accurate predictions of individual DBH and AGB (R2 = .85 and .78, respectively) and of tree size distributions. The proposed method had a higher generalization ability compared to a standard area-based method, in particular for the prediction of the Gini coefficient of DBHs. The delineation method used detected more than 50% of the trees with DBH >10 cm. The detection rate was particularly low for trees with DBH below 10 cm, but they represent a small amount of the total biomass. The Gini coefficient of the DBH distribution was predicted at plot level with R2 = .46. The approach described in this work, easy applicable in different forested areas, is an important development of the traditional area-based remote sensing tools and can be applied for more detailed analysis of forest ecology and dynamics.}, } @article {pmid29938077, year = {2018}, author = {Samuelson, AE and Leadbeater, E}, title = {A land classification protocol for pollinator ecology research: An urbanization case study.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5598-5610}, pmid = {29938077}, issn = {2045-7758}, abstract = {Land-use change is one of the most important drivers of widespread declines in pollinator populations. Comprehensive quantitative methods for land classification are critical to understanding these effects, but co-option of existing human-focussed land classifications is often inappropriate for pollinator research. Here, we present a flexible GIS-based land classification protocol for pollinator research using a bottom-up approach driven by reference to pollinator ecology, with urbanization as a case study. Our multistep method involves manually generating land cover maps at multiple biologically relevant radii surrounding study sites using GIS, with a focus on identifying land cover types that have a specific relevance to pollinators. This is followed by a three-step refinement process using statistical tools: (i) definition of land-use categories, (ii) principal components analysis on the categories, and (iii) cluster analysis to generate a categorical land-use variable for use in subsequent analysis. Model selection is then used to determine the appropriate spatial scale for analysis. We demonstrate an application of our protocol using a case study of 38 sites across a gradient of urbanization in South-East England. In our case study, the land classification generated a categorical land-use variable at each of four radii based on the clustering of sites with different degrees of urbanization, open land, and flower-rich habitat. Studies of land-use effects on pollinators have historically employed a wide array of land classification techniques from descriptive and qualitative to complex and quantitative. We suggest that land-use studies in pollinator ecology should broadly adopt GIS-based multistep land classification techniques to enable robust analysis and aid comparative research. Our protocol offers a customizable approach that combines specific relevance to pollinator research with the potential for application to a wide range of ecological questions, including agroecological studies of pest control.}, } @article {pmid29938076, year = {2018}, author = {Bradfer-Lawrence, T and Gardner, N and Dent, DH}, title = {Canopy bird assemblages are less influenced by habitat age and isolation than understory bird assemblages in Neotropical secondary forest.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5586-5597}, pmid = {29938076}, issn = {2045-7758}, abstract = {Secondary forest habitats are increasingly recognized for their potential to conserve biodiversity in the tropics. However, the development of faunal assemblages in secondary forest systems varies according to habitat quality and species-specific traits. In this study, we predicted that the recovery of bird assemblages is dependent on secondary forest age and level of isolation, the forest stratum examined, and the species' traits of feeding guild and body mass. This study was undertaken in secondary forests in central Panama; spanning a chronosequence of 60-, 90-, and 120-year-old forests, and in neighboring old-growth forest. To give equal attention to all forest strata, we employed a novel method that paired simultaneous surveys in canopy and understory. This survey method provides a more nuanced picture than ground-based studies, which are biased toward understory assemblages. Bird reassembly varied according to both habitat age and isolation, although it was challenging to separate these effects, as the older sites were also more isolated than the younger sites. In combination, habitat age and isolation impacted understory birds more than canopy-dwelling birds. Proportions of dietary guilds did not vary with habitat age, but were significantly different between strata. Body mass distributions were similar across forest ages for small-bodied birds, but older forest supported more large-bodied birds, probably due to control of poaching at these sites. Canopy assemblages were characterized by higher species richness, and greater variation in both dietary breadth and body mass, relative to understory assemblages. The results highlight that secondary forests may offer critical refugia for many bird species, particularly specialist canopy-dwellers. However, understory bird species may be less able to adapt to novel and isolated habitats and should be the focus of conservation efforts encouraging bird colonization of secondary forests.}, } @article {pmid29938075, year = {2018}, author = {Rutter, MT and Roles, AJ and Fenster, CB}, title = {Quantifying natural seasonal variation in mutation parameters with mutation accumulation lines.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5575-5585}, pmid = {29938075}, issn = {2045-7758}, abstract = {Mutations create novel genetic variants, but their contribution to variation in fitness and other phenotypes may depend on environmental conditions. Furthermore, natural environments may be highly heterogeneous. We assessed phenotypes associated with survival and reproductive success in over 30,000 plants representing 100 mutation accumulation lines of Arabidopsis thaliana across four temporal environments at a single field site. In each of the four assays, environmental variance was substantially larger than mutational variance. For some traits, whether mutational variance was significantly varied between seasons. The founder genotype had mean trait values near the mean of the distribution of the mutation accumulation lines in all field experiments. New mutations also contributed more phenotypic variation than would be predicted, given phenotypic and sequence-level divergence among natural populations of A. thaliana. The combination of large environmental variance with a mean effect of mutation near zero suggests that mutations could contribute substantially to standing genetic variation.}, } @article {pmid29938074, year = {2018}, author = {Fofanov, VY and Furstenau, TN and Sanchez, D and Hepp, CM and Cocking, J and Sobek, C and Pagel, N and Walker, F and Chambers, CL}, title = {Guano exposed: Impact of aerobic conditions on bat fecal microbiota.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5563-5574}, pmid = {29938074}, issn = {2045-7758}, abstract = {Bats and their associated guano microbiota provide important terrestrial and subterranean ecosystem services and serve as a reservoir for a wide range of epizootic and zoonotic diseases. Unfortunately, large-scale studies of bats and their guano microbiotas are limited by the time and cost of sample collection, which requires specially trained individuals to work at night to capture bats when they are most active. Indirectly surveying bat gut microbiota through guano deposits could be a more cost-effective alternative, but it must first be established whether the postdefecation exposure to an aerobic environment has a large impact on the guano microbial community. A number of recent studies on mammalian feces have shown that the impact of aerobic exposure is highly species specific; therefore, it is difficult to predict how exposure will affect the bat guano microbiota without empirical data. In our study, we collected fresh guano samples from 24 individuals of 10 bat species that are common throughout the arid environments of the American southwest and subjected the samples to 0, 1, and 12 hr of exposure. The biodiversity decreased rapidly after the shift from an anaerobic to an aerobic environment-much faster than previously reported in mammalian species. However, the relative composition of the core guano microbiota remained stable and, using highly sensitive targeted PCR methods, we found that pathogens present in the original, non-exposed samples could still be recovered after 12 hr of exposure. These results suggest that with careful sample analysis protocols, a more efficient passive collection strategy is feasible; for example, guano could be collected on tarps placed near the roost entrance. Such passive collection methods would greatly reduce the cost of sample collection by allowing more sites or roosts to be surveyed with a fraction of trained personnel, time, and effort investments needed.}, } @article {pmid29938073, year = {2018}, author = {Barak, RS and Lichtenberger, TM and Wellman-Houde, A and Kramer, AT and Larkin, DJ}, title = {Cracking the case: Seed traits and phylogeny predict time to germination in prairie restoration species.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5551-5562}, pmid = {29938073}, issn = {2045-7758}, abstract = {Traits are important for understanding how plant communities assemble and function, providing a common currency for studying ecological processes across species, locations, and habitat types. However, the majority of studies relating species traits to community assembly rely upon vegetative traits of mature plants. Seed traits, which are understudied relative to whole-plant traits, are key to understanding assembly of plant communities. This is particularly true for restored communities, which are typically started de novo from seed, making seed germination a critical first step in community assembly and an early filter for plant establishment. We experimentally tested the effects of seed traits (mass, shape, and embryo to seed size ratio) and phylogeny on germination response in 32 species commonly used in prairie grassland restoration in the Midwestern USA, analyzing data using time-to-event (survival) analysis. As germination is also influenced by seed dormancy, and dormancy break treatments are commonly employed in restoration, we also tested the effects of two pretreatments (cold stratification and gibberellic acid application) on time to germination. Seed traits, phylogeny, and seed pretreatments all affected time to germination. Of all traits tested, variables related to seed shape (height and shape variance) best predicted germination response, with high-variance (i.e., pointier and narrower) seeds germinating faster. Phylogenetic position (the location of species on the phylogenetic tree relative to other tested species) was also an important predictor of germination response, that is, closely related species showed similar patterns in time to germination. This was true despite the fact that all measured seed traits showed phylogenetic signal, therefore phylogeny provided residual information that was not already captured by measured seed traits. Seed traits, phylogenetic position, and germination pretreatments were important predictors of germination response for a suite of species commonly used in grassland restoration. Shape traits were especially important, while mass, often the only seed trait used in studies of community assembly, was not a strong predictor of germination timing. These findings illustrate the ecological importance of seed traits that are rarely incorporated into functional studies of plant communities. This information can also be used to advance restoration practice by guiding restoration planning and seed mix design.}, } @article {pmid29938072, year = {2018}, author = {Deschaine, BM and Heysel, AR and Lenhart, BA and Murphy, HA}, title = {Biofilm formation and toxin production provide a fitness advantage in mixed colonies of environmental yeast isolates.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5541-5550}, pmid = {29938072}, issn = {2045-7758}, abstract = {Microbes can engage in social interactions ranging from cooperation to warfare. Biofilms are structured, cooperative microbial communities. Like all cooperative communities, they are susceptible to invasion by selfish individuals who benefit without contributing. However, biofilms are pervasive and ancient, representing the first fossilized life. One hypothesis for the stability of biofilms is spatial structure: Segregated patches of related cooperative cells are able to outcompete unrelated cells. These dynamics have been explored computationally and in bacteria; however, their relevance to eukaryotic microbes remains an open question. The complexity of eukaryotic cell signaling and communication suggests the possibility of different social dynamics. Using the tractable model yeast, Saccharomyces cerevisiae, which can form biofilms, we investigate the interactions of environmental isolates with different social phenotypes. We find that biofilm strains spatially exclude nonbiofilm strains and that biofilm spatial structure confers a consistent and robust fitness advantage in direct competition. Furthermore, biofilms may protect against killer toxin, a warfare phenotype. During biofilm formation, cells are susceptible to toxin from nearby competitors; however, increased spatial use may provide an escape from toxin producers. Our results suggest that yeast biofilms represent a competitive strategy and that principles elucidated for the evolution and stability of bacterial biofilms may apply to more complex eukaryotes.}, } @article {pmid29938071, year = {2018}, author = {Kauffman, JB and Bernardino, AF and Ferreira, TO and Bolton, NW and Gomes, LEO and Nobrega, GN}, title = {Shrimp ponds lead to massive loss of soil carbon and greenhouse gas emissions in northeastern Brazilian mangroves.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5530-5540}, pmid = {29938071}, issn = {2045-7758}, abstract = {Mangroves of the semiarid Caatinga region of northeastern Brazil are being rapidly converted to shrimp pond aquaculture. To determine ecosystem carbon stocks and potential greenhouse gas emissions from this widespread land use, we measured carbon stocks of eight mangrove forests and three shrimp ponds in the Acaraú and Jaguaribe watersheds in Ceará state, Brazil. The shrimp ponds were paired with adjacent intact mangroves to ascertain carbon losses and potential emissions from land conversion. The mean total ecosystem carbon stock of mangroves in this semiarid tropical landscape was 413 ± 94 Mg C/ha. There were highly significant differences in the ecosystem carbon stocks between the two sampled estuaries suggesting caution when extrapolating carbon stock across different estuaries even in the same landscape. Conversion of mangroves to shrimp ponds resulted in losses of 58%-82% of the ecosystem carbon stocks. The mean potential emissions arising from mangrove conversion to shrimp ponds was 1,390 Mg CO2e/ha. Carbon losses were largely from soils which accounted for 81% of the total emission. Losses from soils >100 cm in depth accounted for 33% of the total ecosystem carbon loss. Soil carbon losses from shrimp pond conversion are equivalent to about 182 years of soil carbon accumulation. Losses from mangrove conversion are about 10-fold greater than emissions from conversion of upland tropical dry forest in the Brazilian Caatinga underscoring the potential value for their inclusion in climate change mitigation activities.}, } @article {pmid29938070, year = {2018}, author = {English, PA and Nocera, JJ and Green, DJ}, title = {Nightjars may adjust breeding phenology to compensate for mismatches between moths and moonlight.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5515-5529}, pmid = {29938070}, issn = {2045-7758}, abstract = {Phenology match-mismatch usually refers to the extent of an organism's ability to match reproduction with peaks in food availability, but when mismatch occurs, it may indicate a response to another selective pressure. We assess the value of matching reproductive timing to multiple selective pressures for a migratory lunarphilic aerial insectivore bird, the whip-poor-will (Antrostomus vociferus). We hypothesize that a whip-poor-will's response to shifts in local phenology may be constrained by long annual migrations and a foraging mode that is dependent on both benign weather and the availability of moonlight. To test this, we monitored daily nest survival and overall reproductive success relative to food availability and moon phase in the northern part of whip-poor-will's breeding range. We found that moth abundance, and potentially temperature and moonlight, may all have a positive influence on daily chick survival rates and that the lowest chick survival rates for the period between hatching and fledging occurred when hatch was mismatched with both moths and moonlight. However, rather than breeding too late for peak moth abundance, the average first brood hatch date actually preceded the peak moth abundance and occurred during a period with slightly higher available moonlight than the period of peak food abundance. As a result, a low individual survival rate was partially compensated for by initiating more nesting attempts. This suggests that nightjars were able to adjust their breeding phenology in such a way that the costs of mismatch with food supply were at least partially balanced by a longer breeding season.}, } @article {pmid29938069, year = {2018}, author = {Edelsparre, AH and Shahid, A and Fitzpatrick, MJ}, title = {Habitat connectivity is determined by the scale of habitat loss and dispersal strategy.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5508-5514}, pmid = {29938069}, issn = {2045-7758}, abstract = {Understanding factors that ameliorate the impact of habitat loss is a major focus of conservation research. One key factor influencing species persistence and evolution is the ability to disperse across increasingly patchy landscapes. Here we ask whether interpatch distance (a proxy for habitat loss) and dispersal strategy can interact to form thresholds where connectivity breaks down. We assayed dispersal across a range of interpatch distances in fruit flies carrying allelic variants of a gene known to underlie differences in dispersal strategy. Dispersal-limited flies experienced a distinct negative threshold in connectivity at greater interpatch distances, and this was not observed in more dispersive flies. Consequently, this differential response of dispersal-limited and more dispersive flies to decreasing connectivity suggests that habitat loss could have important implications on the evolution and maintenance of genetic variation underlying dispersal strategy.}, } @article {pmid29938068, year = {2018}, author = {Raffini, F and Fruciano, C and Meyer, A}, title = {Gene(s) and individual feeding behavior: Exploring eco-evolutionary dynamics underlying left-right asymmetry in the scale-eating cichlid fish Perissodus microlepis.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5495-5507}, pmid = {29938068}, issn = {2045-7758}, abstract = {The scale-eating cichlid fish Perissodus microlepis is a textbook example of bilateral asymmetry due to its left or right-bending heads and of negative frequency-dependent selection, which is proposed to maintain this stable polymorphism. The mechanisms that underlie this asymmetry remain elusive. Several studies had initially postulated a simple genetic basis for this trait, but this explanation has been questioned, particularly by reports observing a unimodal distribution of mouth shapes. We hypothesize that this unimodal distribution might be due to a combination of genetic and phenotypically plastic components. Here, we expanded on previous work by investigating a formerly identified candidate SNP associated to mouth laterality, documenting inter-individual variation in feeding preference using stable isotope analyses, and testing their association with mouth asymmetry. Our results suggest that this polymorphism is influenced by both a polygenic basis and inter-individual non-genetic variation, possibly due to feeding experience, individual specialization, and intraspecific competition. We introduce a hypothesis potentially explaining the simultaneous maintenance of left, right, asymmetric and symmetric mouth phenotypes due to the interaction between diverse eco-evolutionary dynamics including niche construction and balancing selection. Future studies will have to further tease apart the relative contribution of genetic and environmental factors and their interactions in an integrated fashion.}, } @article {pmid29938067, year = {2018}, author = {Hallmann, K and Griebeler, EM}, title = {An exploration of differences in the scaling of life history traits with body mass within reptiles and between amniotes.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5480-5494}, pmid = {29938067}, issn = {2045-7758}, abstract = {Allometric relationships linking species characteristics to body size or mass (scaling) are important in biology. However, studies on the scaling of life history traits in the reptiles (the nonavian Reptilia) are rather scarce, especially for the clades Crocodilia, Testudines, and Rhynchocephalia (single extant species, the tuatara). Previous studies on the scaling of reptilian life history traits indicated that they differ from those seen in the other amniotes (mammals and birds), but so far most comparative studies used small species samples and also not phylogenetically informed analyses. Here, we analyzed the scaling of nine life history traits with adult body mass for crocodiles (n = 22), squamates (n = 294), turtles (n = 52), and reptiles (n = 369). We used for the first time a phylogenetically informed approach for crocodiles, turtles, and the whole group of reptiles. We explored differences in scaling relationships between the reptilian clades Crocodilia, Squamata, and Testudines as well as differences between reptiles, mammals, and birds. Finally, we applied our scaling relationships, in order to gain new insights into the degree of the exceptionality of the tuatara's life history within reptiles. We observed for none of the life history traits studied any difference in their scaling with body mass between squamates, crocodiles, and turtles, except for clutch size and egg weight showing small differences between these groups. Compared to birds and mammals, scaling relationships of reptiles were similar for time-related traits, but they differed for reproductive traits. The tuatara's life history is more similar to that of a similar-sized turtle or crocodile than to a squamate.}, } @article {pmid29938066, year = {2018}, author = {Campos, CM and Velez, S and Miguel, MF and Papú, S and Cona, MI}, title = {Studying the quantity component of seed dispersal effectiveness from exclosure treatments and camera trapping.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5470-5479}, pmid = {29938066}, issn = {2045-7758}, abstract = {The quantity component of effectiveness of seed dispersal by animals is determined by two events: fruit removal (intensity of the interaction) and animal visitation to the plant (frequency of interactions). Considering dispersal of Prosopis flexuosa seeds as case study, this work aimed at investigating the strengths and weaknesses of the two methods for assessing the quantity component of seed dispersal effectiveness: exclosures and camera traps. Prosopis fruits were offered for 48 hr. Exclosure treatments were performed using two types of wire-screen cages, allowing access to ants ("closed exclosure") and to small mammals up to 100 g ("open to small mammals"), and a treatment without exclosure ("open to all removers"). The camera trapping experiment was carried out using vertically oriented cameras placed at approximately 1.80 m height and focused on the fruits. The cameras were set in "motion detect mode," taking series of three consecutive photographs. The exclosures largely allowed estimation of fruit removal by size-based groups of animals, but did not provide information on species identity. In contrast, camera traps were able to identify all visitors to species level and could not only determine the number of visits by each species but also the proportion of visits, which resulted in removal of fruits. Camera trapping allowed discriminating among small mammals playing different roles, without underestimating fruit removal by scatter-hoarding species. The quality of estimation of the quantity component of seed dispersal is remarkably better when the camera trapping method is applied. Additional information obtained, such as activity patterns of visitors, can contribute to a better understanding of the seed dispersal process.}, } @article {pmid29938065, year = {2018}, author = {Tao, ZB and Ren, ZX and Bernhardt, P and Liang, H and Li, HD and Zhao, YH and Wang, H and Li, DZ}, title = {Does reproductive isolation reflect the segregation of color forms in Spiranthes sinensis (Pers.) Ames complex (Orchidaceae) in the Chinese Himalayas?.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5455-5469}, pmid = {29938065}, issn = {2045-7758}, abstract = {Isolation between species, or taxa sharing a common lineage, depends primarily on the relative strengths of various reproductive barriers. Previous studies on reproductive isolation between orchids emphasized mechanical and ethological barriers in flowers of species showing food and/or sexual mimicry. In this study, we investigated and quantified a series of prepollination and postpollination barriers between pink and white forms of Spiranthes sinensis sl, a nectar-secreting complex. We generated ML trees based on trnS-G and matK to explore phylogenetic relationships in this species complex. Spiranthes sinensis sl segregated from some other congeners, but the white form constituted a distinct clade in relation to the pink form. The white form secreted 2-Phenylethanol as it is a single-scent compound and was pollinated almost exclusively by native, large-bodied Apis cerana and Bombus species (Apidae). Apis cerana showed a high floral constancy to this form. The scentless, pink form was pollinated primarily by smaller bees in the genera Ceratina (Apidae), and members of the family Halictidae, with infrequent visits by A. cerana and Bombus species. Fruit set and the production of large embryos following interform pollination treatments were significantly lower compared to intraform pollination results for the white form. Our results suggested that pollinator isolation, based on color and scent cues, may result in greater floral constancy in white populations when both forms are sympatric as two different, guilds of pollinators forage selectively preventing or reducing prospective gene flow. Postpollination barriers appear weaker than prepollination barriers but they also play a role in interform isolation, especially in the white form. Our findings suggest that floral color forms in S. sinensis do not represent an unbalanced polymorphism. Interpretations of the evolutionary status of these forms are discussed.}, } @article {pmid29938064, year = {2018}, author = {Amuzu, HE and Tsyganov, K and Koh, C and Herbert, RI and Powell, DR and McGraw, EA}, title = {Wolbachia enhances insect-specific flavivirus infection in Aedes aegypti mosquitoes.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5441-5454}, pmid = {29938064}, issn = {2045-7758}, abstract = {Mosquitoes transmit a diverse group of human flaviviruses including West Nile, dengue, yellow fever, and Zika viruses. Mosquitoes are also naturally infected with insect-specific flaviviruses (ISFs), a subgroup of the family not capable of infecting vertebrates. Although ISFs are not medically important, they are capable of altering the mosquito's susceptibility to flaviviruses and may alter host fitness. Wolbachia is an endosymbiotic bacterium of insects that when present in mosquitoes limits the replication of co-infecting pathogens, including flaviviruses. Artificially created Wolbachia-infected Aedes aegypti mosquitoes are being released into the wild in a series of trials around the globe with the hope of interrupting dengue and Zika virus transmission from mosquitoes to humans. Our work investigated the effect of Wolbachia on ISF infection in wild-caught Ae. aegypti mosquitoes from field release zones. All field mosquitoes were screened for the presence of ISFs using general degenerate flavivirus primers and their PCR amplicons sequenced. ISFs were found to be common and widely distributed in Ae. aegypti populations. Field mosquitoes consistently had higher ISF infection rates and viral loads compared to laboratory colony material indicating that environmental conditions may modulate ISF infection in Ae. aegypti. Surprisingly, higher ISF infection rates and loads were found in Wolbachia-infected mosquitoes compared to the Wolbachia-free mosquitoes. Our findings demonstrate that the symbiont is capable of manipulating the mosquito virome and that Wolbachia-mediated viral inhibition is not universal for flaviviruses. This may have implications for the Wolbachia-based DENV control strategy if ISFs confer fitness effects or alter mosquito susceptibility to other flaviviruses.}, } @article {pmid29938063, year = {2018}, author = {Zheng, C and Yang, F and Zeng, L and Vargo, EL and Xu, Y}, title = {Genetic diversity and colony structure of Tapinoma melanocephalum on the islands and mainland of South China.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5427-5440}, pmid = {29938063}, issn = {2045-7758}, abstract = {Aim: Tapinoma melanocephalum is listed as one of the most important invasive pest species in China. Information regarding the patterns of invasion and effects of geographic isolation on the population genetics of this species is largely lacking.

Location: South China.

Methods: To address this problem, we genotyped 39 colonies (two colonies were collapsed due to genetic similarity) using microsatellite markers and mitochondrial DNA sequencing to compare colony genetic structure of T. melanocephalum on the mainland and islands of South China.

Results: An analysis of the colony genotypes showed that the genetic diversity of the mainland population was slightly higher than that of the island populations but not significantly so. However, the observed heterozygosity on Shangchuan Island (SCD) was significantly lower than that of the other colonies. We also found six haplotypes in 111 mitochondrial DNA COI sequences. The relatedness (r) value between colonies of SCD was 0.410, higher than that of the other populations. The genetic clusters among colonies were not related to geographic locations and exhibited admixture likely due to frequent human-mediated dispersal associated with trade between the mainland population and the islands. Pairwise FSTs between populations showed differentiation among mainland populations, while SCD displayed high levels of divergence (FST > 0.15) from most mainland populations. There was no significant isolation by distance among colonies. Most populations showed signs of a bottleneck effect.

Main conclusions: Our study suggests that there was no significant difference in the genetic diversity among the islands and the mainland; however, the lower genetic diversity, the higher degree of genetic divergence from other colonies, and the higher relatedness among nestmates made the SCD population stand out from all the others.}, } @article {pmid29938062, year = {2018}, author = {Bellis, ES and Edlund, RB and Berrios, HK and Lessios, HA and Denver, DR}, title = {Molecular signatures of host specificity linked to habitat specialization in Exaiptasia sea anemones.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5413-5426}, pmid = {29938062}, issn = {2045-7758}, abstract = {Rising ocean temperatures associated with global climate change induce breakdown of the symbiosis between coelenterates and photosynthetic microalgae of the genus Symbiodinium. Association with more thermotolerant partners could contribute to resilience, but the genetic mechanisms controlling specificity of hosts for particular Symbiodinium types are poorly known. Here, we characterize wild populations of a sea anemone laboratory model system for anthozoan symbiosis, from contrasting environments in Caribbean Panama. Patterns of anemone abundance and symbiont diversity were consistent with specialization of holobionts for particular habitats, with Exaiptasia pallida/S. minutum (ITS2 type B1) abundant on vertical substrate in thermally stable, shaded environments but E. brasiliensis/Symbiodinium sp. (ITS2 clade A) more common in shallow areas subject to high temperature and irradiance. Population genomic sequencing revealed a novel E. pallida population from the Bocas del Toro Archipelago that only harbors S. minutum. Loci most strongly associated with divergence of the Bocas-specific population were enriched in genes with putative roles in cnidarian symbiosis, including activators of the complement pathway of the innate immune system, thrombospondin-type-1 repeat domain proteins, and coordinators of endocytic recycling. Our findings underscore the importance of unmasking cryptic diversity in natural populations and the role of long-term evolutionary history in mediating interactions with Symbiodinium.}, } @article {pmid29938061, year = {2018}, author = {Cross, TB and Schwartz, MK and Naugle, DE and Fedy, BC and Row, JR and Oyler-McCance, SJ}, title = {The genetic network of greater sage-grouse: Range-wide identification of keystone hubs of connectivity.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5394-5412}, pmid = {29938061}, issn = {2045-7758}, abstract = {Genetic networks can characterize complex genetic relationships among groups of individuals, which can be used to rank nodes most important to the overall connectivity of the system. Ranking allows scarce resources to be guided toward nodes integral to connectivity. The greater sage-grouse (Centrocercus urophasianus) is a species of conservation concern that breeds on spatially discrete leks that must remain connected by genetic exchange for population persistence. We genotyped 5,950 individuals from 1,200 greater sage-grouse leks distributed across the entire species' geographic range. We found a small-world network composed of 458 nodes connected by 14,481 edges. This network was composed of hubs-that is, nodes facilitating gene flow across the network-and spokes-that is, nodes where connectivity is served by hubs. It is within these hubs that the greatest genetic diversity was housed. Using indices of network centrality, we identified hub nodes of greatest conservation importance. We also identified keystone nodes with elevated centrality despite low local population size. Hub and keystone nodes were found across the entire species' contiguous range, although nodes with elevated importance to network-wide connectivity were found more central: especially in northeastern, central, and southwestern Wyoming and eastern Idaho. Nodes among which genes are most readily exchanged were mostly located in Montana and northern Wyoming, as well as Utah and eastern Nevada. The loss of hub or keystone nodes could lead to the disintegration of the network into smaller, isolated subnetworks. Protecting both hub nodes and keystone nodes will conserve genetic diversity and should maintain network connections to ensure a resilient and viable population over time. Our analysis shows that network models can be used to model gene flow, offering insights into its pattern and process, with application to prioritizing landscapes for conservation.}, } @article {pmid29938060, year = {2018}, author = {Camus, MF and Huang, CC and Reuter, M and Fowler, K}, title = {Dietary choices are influenced by genotype, mating status, and sex in Drosophila melanogaster.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5385-5393}, pmid = {29938060}, issn = {2045-7758}, abstract = {Mating causes many changes in physiology, behavior, and gene expression in a wide range of organisms. These changes are predicted to be sex specific, influenced by the divergent reproductive roles of the sexes. In female insects, mating is associated with an increase in egg production which requires high levels of nutritional input with direct consequences for the physiological needs of individual females. Consequently, females alter their nutritional acquisition in line with the physiological demands imposed by mating. Although much is known about the female mating-induced nutritional response, far less is known about changes in males. In addition, it is unknown whether variation between genotypes translates into variation in dietary behavioral responses. Here we examine mating-induced shifts in male and female dietary preferences across genotypes of Drosophila melanogaster. We find sex- and genotype-specific effects on both the quantity and quality of the chosen diet. These results contribute to our understanding of sex-specific metabolism and reveal genotypic variation that influences responses to physiological demands.}, } @article {pmid29938059, year = {2018}, author = {Brydegaard, M and Jansson, S and Schulz, M and Runemark, A}, title = {Can the narrow red bands of dragonflies be used to perceive wing interference patterns?.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5369-5384}, pmid = {29938059}, issn = {2045-7758}, abstract = {Despite numerous studies of selection on position and number of spectral vision bands, explanations to the function of narrow spectral bands are lacking. We investigate dragonflies (Odonata), which have the narrowest spectral bands reported, in order to investigate what features these narrow spectral bands may be used to perceive. We address whether it is likely that narrow red bands can be used to identify conspecifics by the optical signature from wing interference patterns (WIPs). We investigate the optical signatures of Odonata wings using hyperspectral imaging, laser profiling, ellipsometry, polarimetric modulation spectroscopy, and laser radar experiments. Based on results, we estimate the prospects for Odonata perception of WIPs to identify conspecifics in the spectral, spatial, intensity, polarization, angular, and temporal domains. We find six lines of evidence consistent with an ability to perceive WIPs. First, the wing membrane thickness of the studied Odonata is 2.3 μm, coinciding with the maximal thickness perceivable by the reported bandwidth. Second, flat wings imply that WIPs persist from whole wings, which can be seen at a distance. Third, WIPs constitute a major brightness in the visual environment only second after the solar disk. Fourth, WIPs exhibit high degree of polarization and polarization vision coincides with frontal narrow red bands in Odonata. Fifth, the angular light incidence on the Odonata composite eye provides all prerequisites for direct assessment of the refractive index which is associated with age. Sixth, WIPs from conspecifics in flight make a significant contribution even to the fundamental wingbeat frequency within the flicker fusion bandwidth of Odonata vision. We conclude that it is likely that WIPs can be perceived by the narrow red bands found in some Odonata species and propose future behavioral and electrophysiological tests of this hypothesis.}, } @article {pmid29938058, year = {2018}, author = {Fraser, D and Haupt, RJ and Barr, WA}, title = {Phylogenetic signal in tooth wear dietary niche proxies.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5355-5368}, pmid = {29938058}, issn = {2045-7758}, abstract = {In the absence of independent observational data, ecologists and paleoecologists use proxies for the Eltonian niches of species (i.e., the resource or dietary axes of the niche). Some dietary proxies exploit the fact that mammalian teeth experience wear during mastication, due to both tooth-on-tooth and food-on-tooth interactions. The distribution and types of wear detectible at micro- and macroscales are highly correlated with the resource preferences of individuals and, in turn, species. Because methods that quantify the distribution of tooth wear (i.e., analytical tooth wear methods) do so by direct observation of facets and marks on the teeth of individual animals, dietary inferences derived from them are thought to be independent of the clade to which individuals belong. However, an assumption of clade or phylogenetic independence when making species-level dietary inferences may be misleading if phylogenetic niche conservatism is widespread among mammals. Herein, we test for phylogenetic signal in data from numerous analytical tooth wear studies, incorporating macrowear (i.e., mesowear) and microwear (i.e., low-magnification microwear and dental microwear texture analysis). Using two measures of phylogenetic signal, heritability (H2) and Pagel's λ, we find that analytical tooth wear data are not independent of phylogeny and failing to account for such nonindependence leads to overestimation of discriminability among species with different dietary preferences. We suggest that morphological traits inherited from ancestral clades (e.g., tooth shape) influence the ways in which the teeth wear during mastication and constrain the foods individuals of a species can effectively exploit. We do not suggest that tooth wear is simply phylogeny in disguise; the tooth wear of individuals and species likely varies within some range that is set by morphological constraints. We therefore recommend the use of phylogenetic comparative methods in studies of mammalian tooth wear, whenever possible.}, } @article {pmid29938057, year = {2018}, author = {Saarman, N and Burak, M and Opiro, R and Hyseni, C and Echodu, R and Dion, K and Opiyo, EA and Dunn, AW and Amatulli, G and Aksoy, S and Caccone, A}, title = {A spatial genetics approach to inform vector control of tsetse flies (Glossina fuscipes fuscipes) in Northern Uganda.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5336-5354}, pmid = {29938057}, issn = {2045-7758}, support = {D43 TW007391/TW/FIC NIH HHS/United States ; R01 AI068932/AI/NIAID NIH HHS/United States ; T32 AI007404/AI/NIAID NIH HHS/United States ; }, abstract = {Tsetse flies (genus Glossina) are the only vector for the parasitic trypanosomes responsible for sleeping sickness and nagana across sub-Saharan Africa. In Uganda, the tsetse fly Glossina fuscipes fuscipes is responsible for transmission of the parasite in 90% of sleeping sickness cases, and co-occurrence of both forms of human-infective trypanosomes makes vector control a priority. We use population genetic data from 38 samples from northern Uganda in a novel methodological pipeline that integrates genetic data, remotely sensed environmental data, and hundreds of field-survey observations. This methodological pipeline identifies isolated habitat by first identifying environmental parameters correlated with genetic differentiation, second, predicting spatial connectivity using field-survey observations and the most predictive environmental parameter(s), and third, overlaying the connectivity surface onto a habitat suitability map. Results from this pipeline indicated that net photosynthesis was the strongest predictor of genetic differentiation in G. f. fuscipes in northern Uganda. The resulting connectivity surface identified a large area of well-connected habitat in northwestern Uganda, and twenty-four isolated patches on the northeastern margin of the G. f. fuscipes distribution. We tested this novel methodological pipeline by completing an ad hoc sample and genetic screen of G. f. fuscipes samples from a model-predicted isolated patch, and evaluated whether the ad hoc sample was in fact as genetically isolated as predicted. Results indicated that genetic isolation of the ad hoc sample was as genetically isolated as predicted, with differentiation well above estimates made in samples from within well-connected habitat separated by similar geographic distances. This work has important practical implications for the control of tsetse and other disease vectors, because it provides a way to identify isolated populations where it will be safer and easier to implement vector control and that should be prioritized as study sites during the development and improvement of vector control methods.}, } @article {pmid29938056, year = {2018}, author = {Surm, JM and Toledo, TM and Prentis, PJ and Pavasovic, A}, title = {Insights into the phylogenetic and molecular evolutionary histories of Fad and Elovl gene families in Actiniaria.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5323-5335}, pmid = {29938056}, issn = {2045-7758}, abstract = {The biosynthesis of long-chain polyunsaturated fatty acids (LC-PUFAs, ≥ C20) is reliant on the action of desaturase and elongase enzymes, which are encoded by the fatty acyl desaturase (Fad) and elongation of very long-chain fatty acid (Elovl) gene families, respectively. In Metazoa, research investigating the distribution and evolution of these gene families has been restricted largely to Bilateria. Here, we provide insights into the phylogenetic and molecular evolutionary histories of the Fad and Elovl gene families in Cnidaria, the sister phylum to Bilateria. Four model cnidarian genomes and six actiniarian transcriptomes were interrogated. Analysis of the fatty acid composition of a candidate cnidarian species, Actinia tenebrosa, was performed to determine the baseline profile of this species. Phylogenetic analysis revealed lineage-specific gene duplication in actiniarians for both the Fad and Elovl gene families. Two distinct cnidarian Fad clades clustered with functionally characterized Δ5 and Δ6 proteins from fungal and plant species, respectively. Alternatively, only a single cnidarian Elovl clade clustered with functionally characterized Elovl proteins (Elovl4), while two additional clades were identified, one actiniarian-specific (Novel ElovlA) and the another cnidarian-specific (Novel ElovlB). In actiniarians, selection analyses revealed pervasive purifying selection acting on both gene families. However, codons in the Elovl gene family show patterns of nucleotide variation consistent with the action of episodic diversifying selection following gene duplication events. Significantly, these codons may encode amino acid residues that are functionally important for Elovl proteins to target and elongate different precursor fatty acids. In A. tenebrosa, the fatty acid analysis revealed an absence of LC-PUFAs > C20 molecules and implies that the Elovl enzymes are not actively contributing to the elongation of these LC-PUFAs. Overall, this study has revealed that actiniarians possess Fad and Elovl genes required for the biosynthesis of some LC-PUFAs, and that these genes appear to be distinct from bilaterians.}, } @article {pmid29938055, year = {2018}, author = {Godoy, BS and Camargos, LM and Lodi, S}, title = {When phylogeny and ecology meet: Modeling the occurrence of Trichoptera with environmental and phylogenetic data.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5313-5322}, pmid = {29938055}, issn = {2045-7758}, abstract = {Ecological studies are increasingly considering phylogenetic relationships among species. The phylogeny is used as a proxy or filter to improve statistical tests and retain evolutionary elements, such as niche conservation. We used the phylogenetic topology to improve the model for occurrence of Trichoptera genera in Cerrado (Brazilian Savanna) streams. We tested whether parameters generated by logistic models of occurrence, using phylogenetic signals, are better than models generated without phylogenetic information. We used a model with Bayesian updating to examine the influence of stream water pH and phylogenetic relationship among genera on the occurrence of Trichoptera genera. Then, we compared this model with the logistic model for each Trichoptera genus. The probability of occurrence of most genera increased with water pH, and the phylogeny-based explicit logistic model improved the parameters estimated for observed genera. The inferred relationship between genera occurrence and stream pH improved, indicating that phylogeny adds relevant information when estimating ecological responses of organisms. Water with elevated acidity (low pH values) may be restrictive for the occurrence of Trichoptera larvae, especially if the regional streams exhibit neutral to alkaline water, as is observed in the Cerrado region. Using phylogeny-based modeling to predict species occurrence is a prominent opportunity to extend our current statistical framework based on environmental conditions, as it enables a more precise estimation of ecological parameters.}, } @article {pmid29938054, year = {2018}, author = {Revell, LJ}, title = {Comparing the rates of speciation and extinction between phylogenetic trees.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5303-5312}, pmid = {29938054}, issn = {2045-7758}, abstract = {Over the past decade or so it has become increasingly popular to use reconstructed evolutionary trees to investigate questions about the rates of speciation and extinction. Although the methodology of this field has grown substantially in its sophistication in recent years, here I will take a step back to present a very simple model that is designed to investigate the relatively straightforward question of whether the tempo of diversification (speciation and extinction) differs between two or more phylogenetic trees, without attempting to attribute a causal basis to this difference. It is a likelihood method, and I demonstrate that it generally shows type I error that is close to the nominal level. I also demonstrate that parameter estimates obtained with this approach are largely unbiased. As this method can be used to compare trees of unknown relationship, it will be particularly well-suited to problems in which a difference in diversification rate between clades is suspected, but in which these clades are not particularly closely related. As diversification methods can easily take into account an incomplete sampling fraction, but missing lineages are assumed to be missing at random, this method is also appropriate for cases in which we have hypothesized a difference in the process of diversification between two or more focal clades, but in which many unsampled groups separate the few of interest. The method of this study is by no means an attempt to replace more sophisticated models in which, for instance, diversification depends on the state of an observed or unobserved discrete or continuous trait. Rather, my intention is to provide a complementary approach for circumstances in which a simpler hypothesis is warranted and of biological interest.}, } @article {pmid29938053, year = {2018}, author = {Valentin, RE and Lockwood, JL and Mathys, BA and Fonseca, DM}, title = {Influence of invasion history on rapid morphological divergence across island populations of an exotic bird.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5291-5302}, pmid = {29938053}, issn = {2045-7758}, abstract = {There is increasing evidence that exotic populations may rapidly differentiate from those in their native range and that differences also arise among populations within the exotic range. Using morphological and DNA-based analyses, we document the extent of trait divergence among native North American and exotic Hawaiian populations of northern cardinal (Cardinalis cardinalis). Furthermore, using a combination of historical records and DNA-based analyses, we evaluate the role of founder effects in producing observed trait differences. We measured and compared key morphological traits across northern cardinal populations in the native and exotic ranges to assess whether trait divergence across the Hawaiian Islands, where this species was introduced between 1929 and 1931, reflected observed variation across native phylogeographic clades in its native North America. We used and added to prior phylogenetic analyses based on a mitochondrial locus to identify the most likely native source clade(s) for the Hawaiian cardinal populations. We then used Approximate Bayesian Computation (ABC) to evaluate the role of founder effects in producing the observed differences in body size and bill morphology across native and exotic populations. We found cardinal populations on the Hawaiian Islands had morphological traits that diverged substantially across islands and overlapped the trait space of all measured native North American clades. The phylogeographic analysis identified the eastern North American clade (C. cardinalis cardinalis) as the most likely and sole native source for all the Hawaiian cardinal populations. The ABC analyses supported written accounts of the cardinal's introduction that indicate the original 300 cardinals shipped to Hawaii were simultaneously and evenly released across Hawaii, Kauai, and Oahu. Populations on each island likely experienced bottlenecks followed by expansion, with cardinals from the island of Hawaii eventually colonizing Maui unaided. Overall, our results suggest that founder effects had limited impact on morphological trait divergence of exotic cardinal populations in the Hawaiian archipelago, which instead reflect postintroduction events.}, } @article {pmid29938052, year = {2018}, author = {Sebens, KP and Sarà, G and Carrington, E}, title = {Estimation of fitness from energetics and life-history data: An example using mussels.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5279-5290}, pmid = {29938052}, issn = {2045-7758}, abstract = {Changing environments have the potential to alter the fitness of organisms through effects on components of fitness such as energy acquisition, metabolic cost, growth rate, survivorship, and reproductive output. Organisms, on the other hand, can alter aspects of their physiology and life histories through phenotypic plasticity as well as through genetic change in populations (selection). Researchers examining the effects of environmental variables frequently concentrate on individual components of fitness, although methods exist to combine these into a population level estimate of average fitness, as the per capita rate of population growth for a set of identical individuals with a particular set of traits. Recent advances in energetic modeling have provided excellent data on energy intake and costs leading to growth, reproduction, and other life-history parameters; these in turn have consequences for survivorship at all life-history stages, and thus for fitness. Components of fitness alone (performance measures) are useful in determining organism response to changing conditions, but are often not good predictors of fitness; they can differ in both form and magnitude, as demonstrated in our model. Here, we combine an energetics model for growth and allocation with a matrix model that calculates population growth rate for a group of individuals with a particular set of traits. We use intertidal mussels as an example, because data exist for some of the important energetic and life-history parameters, and because there is a hypothesized energetic trade-off between byssus production (affecting survivorship), and energy used for growth and reproduction. The model shows exactly how strong this trade-off is in terms of overall fitness, and it illustrates conditions where fitness components are good predictors of actual fitness, and cases where they are not. In addition, the model is used to examine the effects of environmental change on this trade-off and on both fitness and on individual fitness components.}, } @article {pmid29938051, year = {2018}, author = {Cowles, J and Boldgiv, B and Liancourt, P and Petraitis, PS and Casper, BB}, title = {Effects of increased temperature on plant communities depend on landscape location and precipitation.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5267-5278}, pmid = {29938051}, issn = {2045-7758}, abstract = {Global climate change is affecting and will continue to affect ecosystems worldwide. Specifically, temperature and precipitation are both expected to shift globally, and their separate and interactive effects will likely affect ecosystems differentially depending on current temperature, precipitation regimes, and other biotic and environmental factors. It is not currently understood how the effects of increasing temperature on plant communities may depend on either precipitation or where communities lie on soil moisture gradients. Such knowledge would play a crucial role in increasing our predictive ability for future effects of climate change in different systems. To this end, we conducted a multi-factor global change experiment at two locations, differing in temperature, moisture, aspect, and plant community composition, on the same slope in the northern Mongolian steppe. The natural differences in temperature and moisture between locations served as a point of comparison for the experimental manipulations of temperature and precipitation. We conducted two separate experiments, one examining the effect of climate manipulation via open-top chambers (OTCs) across the two different slope locations, the other a factorial OTC by watering experiment at one of the two locations. By combining these experiments, we were able to assess how OTCs impact plant productivity and diversity across a natural and manipulated range of soil moisture. We found that warming effects were context dependent, with the greatest negative impacts of warming on diversity in the warmer, drier upper slope location and in the unwatered plots. Our study is an important step in understanding how global change will affect ecosystems across multiple scales and locations.}, } @article {pmid29938050, year = {2018}, author = {Lamb, T and Justice, TC and Brewer, MS and Moler, PE and Hopkins, H and Bond, JE}, title = {A biogeographical profile of the sand cockroach Arenivaga floridensis and its bearing on origin hypotheses for Florida scrub biota.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5254-5266}, pmid = {29938050}, issn = {2045-7758}, abstract = {Florida scrub is a xeric ecosystem associated with the peninsula's sand ridges, whose intermittent Pliocene-Pleistocene isolation is considered key to scrub endemism. One scrub origin hypothesis posits endemics were sourced by the Pliocene dispersal of arid-adapted taxa from southwestern North America; a second invokes Pleistocene migration within eastern North America. Only one study to date has explicitly tested these competing hypotheses, supporting an eastern origin for certain scrub angiosperms. For further perspective, we conducted a genetic analysis of an endemic arthropod, the Florida sand cockroach (Arenivaga floridensis), with two aims: (1) to reconstruct the peninsular colonization and residence history of A. floridensis and (2) determine whether its biogeographic profile favors either origin hypothesis. We sequenced the cox2 mitochondrial gene for 237 specimens (65 populations) as well as additional loci (cox1, nuclear H3) for a subset of Florida roaches and congeners. Using Network and Bayesian inference methods, we identified three major lineages whose genetic differentiation and phylogeographical structure correspond with late Pliocene peninsula insularization, indicating Arenivaga was present and broadly distributed in Florida at that time. Stem and crown divergence estimates (6.36 Ma; 2.78 Ma) between A. floridensis and western sister taxa span a period of extensive dispersal by western biota along an arid Gulf Coast corridor. These phylogeographical and phylogenetic results yield a biogeographic profile consistent with the western origin hypothesis. Moreover, age estimates for the roach's peninsular residence complement those of several other endemics, favoring a Pliocene (or earlier) inception of the scrub ecosystem. We argue that eastern versus western hypotheses are not mutually exclusive; rather, a composite history of colonization involving disparate biotas better explains the diverse endemism of Florida scrub.}, } @article {pmid29938049, year = {2018}, author = {Duarte, S and Nobre, T and Borges, PAV and Nunes, L}, title = {Symbiotic flagellate protists as cryptic drivers of adaptation and invasiveness of the subterranean termite Reticulitermes grassei Clément.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5242-5253}, pmid = {29938049}, issn = {2045-7758}, abstract = {Changes in flagellate protist communities of subterranean termite Reticulitermes grassei across different locations were evaluated following four predictions: (i) Rural endemic (Portugal mainland) termite populations will exhibit high diversity of symbionts; (ii) invasive urban populations (Horta city, Faial island, Azores), on the contrary, will exhibit lower diversity of symbionts, showing high similarity of symbiont assemblages through environmental filtering; (iii) recent historical colonization of isolated regions-as the case of islands-will imply a loss of symbiont diversity; and (iv) island isolation will trigger a change in colony breeding structure toward a less aggressive behavior. Symbiont flagellate protist communities were morphologically identified, and species richness and relative abundances, as well as biodiversity indices, were used to compare symbiotic communities in colonies from urban and rural environments and between island invasive and mainland endemic populations. To evaluate prediction on the impact of isolation (iv), aggression tests were performed among termites comprising island invasive and mainland endemic populations. A core group of flagellates and secondary facultative symbionts was identified. Termites from rural environments showed, in the majority of observed colonies, more diverse and abundant protist communities, probably confirming prediction (i). Corroborating prediction (ii), the two least diverse communities belong to termites captured inside urban areas. The Azorean invasive termite colonies had more diverse protist communities than expected and prediction (iii) which was not verified within this study. Termites from mainland populations showed a high level of aggressiveness between neighboring colonies, in contrast to the invasive colonies from Horta city, which were not aggressive to neighbors according to prediction (iv). The symbiotic flagellate community of R. grassei showed the ability to change in a way that might be consistent with adaptation to available conditions, possibly contributing to optimization of the colonization of new habitats and spreading of its distribution area, highlighting R. grassei potential as an invasive species.}, } @article {pmid29938048, year = {2018}, author = {Davy, CM and Donaldson, ME and Willis, CKR and Saville, BJ and McGuire, LP and Mayberry, H and Wilcox, A and Wibbelt, G and Misra, V and Kyle, CJ}, title = {Environmentally persistent pathogens present unique challenges for studies of host-pathogen interactions: Reply to Field (2018).}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5238-5241}, pmid = {29938048}, issn = {2045-7758}, abstract = {Linked article: https://doi.org/10.1002/ece3.4034.}, } @article {pmid29938047, year = {2018}, author = {Field, KA}, title = {Quantification of pathogen levels is necessary to compare responses to pathogen exposure: Comment on Davy et al. "The other white-nose syndrome transcriptome".}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5235-5237}, pmid = {29938047}, issn = {2045-7758}, abstract = {When studying host responses to the presence of pathogens, the pathogen levels should be verified within the samples. The RNA-Seq samples from Davy et al. (2017) do not contain detectable Pseudogymnoascus destructans pathogen levels compared to other studies. Future studies will be necessary to determine how hosts resistant to white-nose syndrome respond differently than susceptible hosts at the whole-transcriptome level. Linked Article: https://doi.org/10.1002/ece3.4035.}, } @article {pmid29938046, year = {2018}, author = {Terando, A and Youngsteadt, E and Meineke, E and Prado, S}, title = {Accurate near surface air temperature measurements are necessary to gauge large-scale ecological responses to global climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5233-5234}, pmid = {29938046}, issn = {2045-7758}, abstract = {Linked Article: https://doi.org/10.1002/ece3.3965.}, } @article {pmid29938045, year = {2018}, author = {Ashcroft, MB}, title = {Which is more biased: Standardized weather stations or microclimatic sensors?.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5231-5232}, pmid = {29938045}, issn = {2045-7758}, abstract = {Linked Article: https://doi.org/10.1002/ece3.3972.}, } @article {pmid29938044, year = {2018}, author = {Arrontes, J}, title = {Pop-Inference: An educational application to evaluate statistical differences among populations.}, journal = {Ecology and evolution}, volume = {8}, number = {11}, pages = {5224-5230}, pmid = {29938044}, issn = {2045-7758}, abstract = {Pop-Inference is an educational tool designed to help teaching of hypothesis testing using populations. The application allows for the statistical comparison of demographic parameters among populations. Input demographic data are projection matrices or raw demographic data. Randomization tests are used to compare populations. The tests evaluate the hypothesis that demographic parameters differ among groups of individuals more that should be expected from random allocation of individuals to populations. Confidence intervals for demographic parameters are obtained using the bootstrap. Tests may be global or pairwise. In addition to tests on differences, one-way life table response experiments (LTRE) are available for random and fixed factors. Planned (a priori) comparisons are possible. Power of comparison tests is evaluated by constructing the distribution of the test statistic when the null hypothesis is true and when it is false. The relationship between power and sample size is explored by evaluating differences among populations at increasing population sizes, while keeping vital rates constant.}, } @article {pmid29938017, year = {2018}, author = {Sullivan, MJP and Lewis, SL and Hubau, W and Qie, L and Baker, TR and Banin, LF and Chave, J and Cuni-Sanchez, A and Feldpausch, TR and Lopez-Gonzalez, G and Arets, E and Ashton, P and Bastin, JF and Berry, NJ and Bogaert, J and Boot, R and Brearley, FQ and Brienen, R and Burslem, DFRP and de Canniere, C and Chudomelová, M and Dančák, M and Ewango, C and Hédl, R and Lloyd, J and Makana, JR and Malhi, Y and Marimon, BS and Junior, BHM and Metali, F and Moore, S and Nagy, L and Vargas, PN and Pendry, CA and Ramírez-Angulo, H and Reitsma, J and Rutishauser, E and Salim, KA and Sonké, B and Sukri, RS and Sunderland, T and Svátek, M and Umunay, PM and Martinez, RV and Vernimmen, RRE and Torre, EV and Vleminckx, J and Vos, V and Phillips, OL}, title = {Field methods for sampling tree height for tropical forest biomass estimation.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {5}, pages = {1179-1189}, pmid = {29938017}, issn = {2041-210X}, abstract = {Quantifying the relationship between tree diameter and height is a key component of efforts to estimate biomass and carbon stocks in tropical forests. Although substantial site-to-site variation in height-diameter allometries has been documented, the time consuming nature of measuring all tree heights in an inventory plot means that most studies do not include height, or else use generic pan-tropical or regional allometric equations to estimate height.Using a pan-tropical dataset of 73 plots where at least 150 trees had in-field ground-based height measurements, we examined how the number of trees sampled affects the performance of locally derived height-diameter allometries, and evaluated the performance of different methods for sampling trees for height measurement.Using cross-validation, we found that allometries constructed with just 20 locally measured values could often predict tree height with lower error than regional or climate-based allometries (mean reduction in prediction error = 0.46 m). The predictive performance of locally derived allometries improved with sample size, but with diminishing returns in performance gains when more than 40 trees were sampled. Estimates of stand-level biomass produced using local allometries to estimate tree height show no over- or under-estimation bias when compared with biomass estimates using field measured heights. We evaluated five strategies to sample trees for height measurement, and found that sampling strategies that included measuring the heights of the ten largest diameter trees in a plot outperformed (in terms of resulting in local height-diameter models with low height prediction error) entirely random or diameter size-class stratified approaches.Our results indicate that even limited sampling of heights can be used to refine height-diameter allometries. We recommend aiming for a conservative threshold of sampling 50 trees per location for height measurement, and including the ten trees with the largest diameter in this sample.}, } @article {pmid29938016, year = {2018}, author = {Halperin, T and Kalyuzhny, M and Hawlena, D}, title = {How to use (and not to use) movement-based indices for quantifying foraging behaviour.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {4}, pages = {1088-1096}, pmid = {29938016}, issn = {2041-210X}, abstract = {Movement-based indices such as moves per minute (MPM) and proportion time moving (PTM) are common methodologies to quantify foraging behaviour. We explore fundamental drawbacks of these indices that question the ways scientists have been using them and propose new solutions.To do so, we combined analytical and simulation models with lizards foraging data at the individual and species levels.We found that the maximal value of MPM is constrained by the minimal durations of moves and stops. As a result, foragers that rarely move and those that rarely stop are bounded to similar low MPM values. This implies that (1) MPM has very little meaning when used alone, (2) MPM and PTM are interdependent, and (3) certain areas in the MPM-PTM plane cannot be occupied. We also found that MPM suffers from inaccuracy and imprecision.We introduced a new bias correction formula for already published MPM data, and a novel index of changes per minute (CPM) that uses the frequency of changes between move and stop bouts. CPM is very similar to MPM, but does not suffer from bias. Finally, we suggested a new foraging plane of average move and average stop durations. We hope that our guidelines of how to use (and not to use) movement-based indices will add rigor to the study of animals' foraging behaviour.}, } @article {pmid29938015, year = {2018}, author = {Beugin, MP and Gayet, T and Pontier, D and Devillard, S and Jombart, T}, title = {A fast likelihood solution to the genetic clustering problem.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {4}, pages = {1006-1016}, pmid = {29938015}, issn = {2041-210X}, abstract = {The investigation of genetic clusters in natural populations is an ubiquitous problem in a range of fields relying on the analysis of genetic data, such as molecular ecology, conservation biology and microbiology. Typically, genetic clusters are defined as distinct panmictic populations, or parental groups in the context of hybridisation. Two types of methods have been developed for identifying such clusters: model-based methods, which are usually computer-intensive but yield results which can be interpreted in the light of an explicit population genetic model, and geometric approaches, which are less interpretable but remarkably faster.Here, we introduce snapclust, a fast maximum-likelihood solution to the genetic clustering problem, which allies the advantages of both model-based and geometric approaches. Our method relies on maximising the likelihood of a fixed number of panmictic populations, using a combination of geometric approach and fast likelihood optimisation, using the Expectation-Maximisation (EM) algorithm. It can be used for assigning genotypes to populations and optionally identify various types of hybrids between two parental populations. Several goodness-of-fit statistics can also be used to guide the choice of the retained number of clusters.Using extensive simulations, we show that snapclust performs comparably to current gold standards for genetic clustering as well as hybrid detection, with some advantages for identifying hybrids after several backcrosses, while being orders of magnitude faster than other model-based methods. We also illustrate how snapclust can be used for identifying the optimal number of clusters, and subsequently assign individuals to various hybrid classes simulated from an empirical microsatellite dataset. snapclust is implemented in the package adegenet for the free software R, and is therefore easily integrated into existing pipelines for genetic data analysis. It can be applied to any kind of co-dominant markers, and can easily be extended to more complex models including, for instance, varying ploidy levels. Given its flexibility and computer-efficiency, it provides a useful complement to the existing toolbox for the study of genetic diversity in natural populations.}, } @article {pmid29938014, year = {2018}, author = {Hagen, O and Stadler, T}, title = {TreeSimGM: Simulating phylogenetic trees under general Bellman-Harris models with lineage-specific shifts of speciation and extinction in R.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {3}, pages = {754-760}, pmid = {29938014}, issn = {2041-210X}, abstract = {Understanding macroevolutionary processes using phylogenetic trees is a challenging and complex process that draws on mathematics, computer science and biology. Given the development of complex mathematical models and the growing computational processing power, simulation tools are becoming increasingly popular.In order to simulate phylogenetic trees, most evolutionary biologists are forced to build their own algorithms or use existing tools built on different platforms and/or as standalone programmes. The absence of a simulation tool accommodating for user-chosen model specifications limits, amongst others, model testing and pipelining with approximate Bayesian computation methods or other subsequent statistical analysis.We introduce "TreeSimGM," an r-package simulation tool for phylogenetic trees under a general Bellman and Harris model. This package allows the user to specify any desired probability distribution for the waiting times until speciation and extinction (e.g. age-dependent speciation/extinction). Upon speciation, the user can specify whether one descendant species corresponds to the ancestor species inheriting its age or whether both descendant species are new species of age 0. Moreover, it is possible to scale the waiting time to speciation/extinction for newly formed species. Thus, "TreeSimGM" not only allows the user to simulate stochastic phylogenetic trees assuming several popular existing models, such as the Yule model, the constant-rate birth-death model, and proportional to distinguishable arrangement models, but it also allows the user to formulate new models for exploration. A short explanation of the supported models and a few examples of how to use our package are presented here.As an r-package, "TreeSimGM" allows flexible and powerful stochastic phylogenetic tree simulations. Moreover, it facilitates the pipelining of outputs or inputs with other functions in r. "TreeSimGM" contributes to the tools available to the r community in the fields of ecology and evolution, is freely available under the GPL-2 licence and can be downloaded at https://cran.r-project.org/web/packages/TreeSimGM.}, } @article {pmid29938013, year = {2018}, author = {Power, EF and Stabler, D and Borland, AM and Barnes, J and Wright, GA}, title = {Analysis of nectar from low-volume flowers: A comparison of collection methods for free amino acids.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {3}, pages = {734-743}, pmid = {29938013}, issn = {2041-210X}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Floral nectar is a reward offered by flowering plants to visiting pollinators. Nectar chemistry is important for understanding plant nutrient allocation and plant-pollinator interactions. However, many plant species are difficult to sample as their flowers are small and produce low amounts of nectar.We compared the effects of different methods of nectar collection on the amino acid composition of flowers with low volumes of nectar. We used five methods to collect nectar from 60 (5 × 12) Calluna vulgaris flowers: microcapillary tubes, a low-volume flower rinse (the micro-rinse method, using 2 μl water), filter paper, a high-volume flower rinse (2 ml water) and a flower wash (2 ml water). We analysed the samples for free amino acids using quantitative UHPLC methods .We found that the micro-rinse method (rinsing the nectary with enough water to only cover the nectary) recovered amino acid proportions similar to raw nectar extracted using microcapillary tubes. The filter paper, 2 ml rinse and 2 ml wash methods measured significantly higher values of free amino acids and also altered the profile of amino acids. We discuss our concerns about the increased contamination risk of the filter paper and high-volume rinse and wash samples from dried nectar across the floral tissue (nectar unavailable to floral visitors), pollen, vascular fluid and cellular fluid.Our study will enable researchers to make informed decisions about nectar collection methods depending on their intended chemical analysis. These methods of sampling will enable researchers to examine a larger array of plant species' flowers to include those with low volumes of nectar.}, } @article {pmid29938012, year = {2018}, author = {Doncaster, CP and Spake, R}, title = {Correction for bias in meta-analysis of little-replicated studies.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {3}, pages = {634-644}, pmid = {29938012}, issn = {2041-210X}, abstract = {Meta-analyses conventionally weight study estimates on the inverse of their error variance, in order to maximize precision. Unbiased variability in the estimates of these study-level error variances increases with the inverse of study-level replication. Here, we demonstrate how this variability accumulates asymmetrically across studies in precision-weighted meta-analysis, to cause undervaluation of the meta-level effect size or its error variance (the meta-effect and meta-variance).Small samples, typical of the ecological literature, induce big sampling errors in variance estimation, which substantially bias precision-weighted meta-analysis. Simulations revealed that biases differed little between random- and fixed-effects tests. Meta-estimation of a one-sample mean from 20 studies, with sample sizes of 3-20 observations, undervalued the meta-variance by c. 20%. Meta-analysis of two-sample designs from 20 studies, with sample sizes of 3-10 observations, undervalued the meta-variance by 15%-20% for the log response ratio (lnR); it undervalued the meta-effect by c. 10% for the standardized mean difference (SMD).For all estimators, biases were eliminated or reduced by a simple adjustment to the weighting on study precision. The study-specific component of error variance prone to sampling error and not parametrically attributable to study-specific replication was replaced by its cross-study mean, on the assumptions of random sampling from the same population variance for all studies, and sufficient studies for averaging. Weighting each study by the inverse of this mean-adjusted error variance universally improved accuracy in estimation of both the meta-effect and its significance, regardless of number of studies. For comparison, weighting only on sample size gave the same improvement in accuracy, but could not sensibly estimate significance.For the one-sample mean and two-sample lnR, adjusted weighting also improved estimation of between-study variance by DerSimonian-Laird and REML methods. For random-effects meta-analysis of SMD from little-replicated studies, the most accurate meta-estimates obtained from adjusted weights following conventionally weighted estimation of between-study variance.We recommend adoption of weighting by inverse adjusted-variance for meta-analyses of well- and little-replicated studies, because it improves accuracy and significance of meta-estimates, and it can extend the scope of the meta-analysis to include some studies without variance estimates.}, } @article {pmid29937540, year = {2018}, author = {Lagier, JC and Dubourg, G and Million, M and Cadoret, F and Bilen, M and Fenollar, F and Levasseur, A and Rolain, JM and Fournier, PE and Raoult, D}, title = {Culturing the human microbiota and culturomics.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {540-550}, doi = {10.1038/s41579-018-0041-0}, pmid = {29937540}, issn = {1740-1534}, abstract = {The gut microbiota has an important role in the maintenance of human health and in disease pathogenesis. This importance was realized through the advent of omics technologies and their application to improve our knowledge of the gut microbial ecosystem. In particular, the use of metagenomics has revealed the diversity of the gut microbiota, but it has also highlighted that the majority of bacteria in the gut remain uncultured. Culturomics was developed to culture and identify unknown bacteria that inhabit the human gut as a part of the rebirth of culture techniques in microbiology. Consisting of multiple culture conditions combined with the rapid identification of bacteria, the culturomic approach has enabled the culture of hundreds of new microorganisms that are associated with humans, providing exciting new perspectives on host-bacteria relationships. In this Review, we discuss why and how culturomics was developed. We describe how culturomics has extended our understanding of bacterial diversity and then explore how culturomics can be applied to the study of the human microbiota and the potential implications for human health.}, } @article {pmid29937414, year = {2018}, author = {Rivero, A and Gandon, S}, title = {Evolutionary Ecology of Avian Malaria: Past to Present.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {712-726}, doi = {10.1016/j.pt.2018.06.002}, pmid = {29937414}, issn = {1471-5007}, mesh = {Animals ; *Biological Evolution ; Birds ; *Host-Parasite Interactions ; Malaria, Avian/*parasitology ; Plasmodium/physiology ; }, abstract = {Avian malaria is the oldest experimental system for investigating the biology and transmission of Plasmodium parasites. Recent molecular protocols for detecting and characterizing avian malaria lineages in the field are providing an ever-growing picture of the prevalence, distribution, host range, and diversity hotspots of avian malaria across the world. The unparalleled genetic diversity uncovered rivals anything that has been found in other vertebrate malarias and seems to be matched by an equally rich phenotypic diversity, providing endless opportunities for exploring the selective pressures under which hosts and parasites evolve. We review the most important milestones in avian Plasmodium research and explain why this is a unique animal model to understand the ecology and evolution of malaria.}, } @article {pmid29937307, year = {2018}, author = {Coutinho, FH and Gregoracci, GB and Walter, JM and Thompson, CC and Thompson, FL}, title = {Metagenomics Sheds Light on the Ecology of Marine Microbes and Their Viruses.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {955-965}, doi = {10.1016/j.tim.2018.05.015}, pmid = {29937307}, issn = {1878-4380}, abstract = {Advances brought about by omics-based approaches have revolutionized our understanding of the diversity and ecological processes involving marine archaea, bacteria, and their viruses. This broad review discusses recent examples of how genomics, metagenomics, and ecogenomics have been applied to reveal the ecology of these biological entities. Three major topics are covered in this revision: (i) the novel roles of microorganisms in ecosystem processes; (ii) virus-host associations; and (iii) ecological associations of microeukaryotes and other microbes. We also briefly comment on the discovery of novel taxa from marine ecosystems; development of a robust taxonomic framework for prokaryotes; breakthroughs on the diversity and ecology of cyanobacteria; and advances on ecological modelling. We conclude by discussing limitations of the field and suggesting directions for future research.}, } @article {pmid29936914, year = {2018}, author = {Field, DJ and Hsiang, AY}, title = {A North American stem turaco, and the complex biogeographic history of modern birds.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {102}, pmid = {29936914}, issn = {1471-2148}, mesh = {Animals ; Bayes Theorem ; Birds/anatomy & histology/*classification ; Calibration ; Fossils ; Hindlimb/anatomy & histology ; Likelihood Functions ; Phylogeny ; *Phylogeography ; United States ; }, abstract = {BACKGROUND: Earth's lower latitudes boast the majority of extant avian species-level and higher-order diversity, with many deeply diverging clades restricted to vestiges of Gondwana. However, palaeontological analyses reveal that many avian crown clades with restricted extant distributions had stem group relatives in very different parts of the world.

RESULTS: Our phylogenetic analyses support the enigmatic fossil bird Foro panarium Olson 1992 from the early Eocene (Wasatchian) of Wyoming as a stem turaco (Neornithes: Pan-Musophagidae), a clade that is presently endemic to sub-Saharan Africa. Our analyses offer the first well-supported evidence for a stem musophagid (and therefore a useful fossil calibration for avian molecular divergence analyses), and reveal surprising new information on the early morphology and biogeography of this clade. Total-clade Musophagidae is identified as a potential participant in dispersal via the recently proposed 'North American Gateway' during the Palaeogene, and new biogeographic analyses illustrate the importance of the fossil record in revealing the complex historical biogeography of crown birds across geological timescales.

CONCLUSIONS: In the Palaeogene, total-clade Musophagidae was distributed well outside the range of crown Musophagidae in the present day. This observation is consistent with similar biogeographic observations for numerous other modern bird clades, illustrating shortcomings of historical biogeographic analyses that do not incorporate information from the avian fossil record.}, } @article {pmid29936520, year = {2018}, author = {York, A}, title = {New drugs underfoot?.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0051-y}, pmid = {29936520}, issn = {1740-1534}, } @article {pmid29936519, year = {2018}, author = {York, A}, title = {Oiling the Flavivirus replication machinery.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0050-z}, pmid = {29936519}, issn = {1740-1534}, } @article {pmid29936513, year = {2018}, author = {Sanders, C and Hall, J and Sanders, C and Dessens, A and Bryce, J and Callens, N and Cools, M and Kourime, M and Kyriakou, A and Springer, A and Audi, L and Balsamo, A and Iotova, V and Mladenov, V and Krawczynski, M and Nordenskjöld, A and Rozas, M and Claahsen-van der Grinten, H and Hiort, O and Riedl, S and Ahmed, SF}, title = {Involving Individuals with Disorders of Sex Development and Their Parents in Exploring New Models of Shared Learning: Proceedings from a DSDnet COST Action Workshop.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000490081}, pmid = {29936513}, issn = {1661-5433}, abstract = {The level of connection between health care professionals and people who experience a condition that affects sex development is variable. These people and associated support groups need to be included in discussions about research and healthcare delivery. The aim of this study was to understand the experiences of individuals with disorders of sexual development (DSD), their parents, health care providers, and support groups. Workshop planning, preparation, delivery, and evaluation involved members of working groups from the COST Action DSDnet. A coordinator, in collaboration with a support group representative, led the workshop design and delivery. Our successful, facilitated workshop involved 33 attendees from 8 EU countries. The workshop provided individuals with DSD, parents, advisory groups, and professionals with an opportunity for shared learning. Outputs focused on 7 key areas, including diagnosis, childhood, and transition to adult care as well as fostering discussion around registries, future research topics, consent processes, and information needs across the life course. The importance of trustworthy and knowledgeable providers, time to understand such rare conditions, and the place support groups have in a life course approach were valuable learning points for all attendees. In conclusion, workshops can be designed and delivered in meaningful ways for all those involved in care of individuals with rare conditions.}, } @article {pmid29936029, year = {2018}, author = {Thorpe, RS and Barlow, A and Surget-Groba, Y and Malhotra, A}, title = {Multilocus phylogeny, species age and biogeography of the Lesser Antillean anoles.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {682-695}, doi = {10.1016/j.ympev.2018.06.014}, pmid = {29936029}, issn = {1095-9513}, abstract = {Lesser Antillean anoles provide classic examples of island radiations. A detailed knowledge of their phylogeny and biogeography, in particular how the age of species relate to the ages of their respective islands and the age of their radiation, is essential to elucidate the tempo and mechanisms of these radiations. We conduct a large-scale phylogenetic and phylogeographic investigation of the Lesser Antillean anoles using multiple genetic markers and comprehensive geographic sampling of most species. The multilocus phylogeny gives the first well-supported reconstruction of the interspecific relationships, and the densely sampled phylogeography reveals a highly dynamic system, driven by overseas dispersal, with several alternative post-dispersal colonisation trajectories. These radiations currently occupy both the outer-older (Eocene to Miocene), and the inner-younger (<8mybp), Lesser Antillean arcs. The origin of these radiations corresponds with the age of the ancient outer arc. However, the ages of extant species (compatible with the age of other small terrestrial amniotes) are much younger, about the age of the emergence of the younger arc, or less. The difference between the age of the radiation and the age of the extant species suggests substantial species turnover on older arc islands, most likely through competitive replacement. Although extant anoles are extremely speciose, this may represent only a fraction of their biodiversity over time. While paraphyly enables us to infer several recent colonization events, the absence of the younger arc islands and extant species at the earlier and middle stages of the radiation, does not allow the earlier inter-island colonization to be reliably inferred. Reproductive isolation in allopatry takes a very considerable time (in excess of 8my) and sympatry appears to occur only late in the radiation. The resolved multilocus phylogeny, and relative species age, raise difficulties for some earlier hypotheses regarding size evolution, and provide no evidence for within-island speciation.}, } @article {pmid29936028, year = {2018}, author = {Nemati, Z and Blattner, FR and Kerndorff, H and Erol, O and Harpke, D}, title = {Phylogeny of the saffron-crocus species group, Crocus series Crocus (Iridaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {891-897}, doi = {10.1016/j.ympev.2018.06.036}, pmid = {29936028}, issn = {1095-9513}, abstract = {Phylogenetic relationships among the taxa of Crocus series Crocus are still unclear, preventing the understanding of species diversity and the evolution of the important spice saffron (Crocus sativus). Therefore, we analyzed sequences of two chloroplast (trnL-trnF, matK-trnK) and three nuclear (TOPO6, ribosomal DNA ETS and ITS) marker regions to infer phylogenetic relationships among all species belonging to series Crocus. Our phylogenetic analyses resolved the relationships among all taxa of the series. Crocus hadriaticus and the former C. pallasii subspecies appeared polyphyletic. The latter deserve elevating the subspecies to species rank, while for C. hadriaticus a detailed study of species boundaries is necessary. Multi-locus and also genome-wide single nucleotide polymorphism data obtained through genotyping-by-sequencing placed C. sativus within C. cartwrightianus with no indication that other Crocus species contributed to the evolution of the triploid. Our analyses thus made an autotriploid origin of C. sativus from C. cartwrightianus very likely.}, } @article {pmid29935995, year = {2018}, author = {Chalkowski, K and Lepczyk, CA and Zohdy, S}, title = {Parasite Ecology of Invasive Species: Conceptual Framework and New Hypotheses.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {655-663}, doi = {10.1016/j.pt.2018.05.008}, pmid = {29935995}, issn = {1471-5007}, mesh = {Animals ; *Ecosystem ; *Host-Parasite Interactions ; *Introduced Species ; Parasites/physiology ; }, abstract = {Biological invasions have the potential to influence parasite dynamics by altering ecological interactions. Similarly, parasitism can influence invasion by aiding or limiting expansion. While many parasite-invasion relationships have been evaluated, many have not been described. Here, we present a conceptual framework of potential interactions, and introduce two new concepts. The first, disease facilitation, nested within the parasite spillback hypothesis, is when invasive species facilitate parasite transmission through habitat alteration or physical transfer. The second, suppressive spillover, is when the deleterious effects of parasitic infection limit the expansion of an introduced species (and hence invasion success). Taken together, the proposed framework may aide in our understanding of ecological drivers of invasion and parasite ecology and can be used to improve mitigation strategies.}, } @article {pmid29935941, year = {2018}, author = {Niu, Y and Sun, H and Stevens, M}, title = {Plant Camouflage: Ecology, Evolution, and Implications.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {608-618}, doi = {10.1016/j.tree.2018.05.010}, pmid = {29935941}, issn = {1872-8383}, abstract = {Camouflage is a key defensive strategy in animals, and it has been used to illustrate and study evolution for 150 years. It is now evident that many camouflage concepts likely also apply to plants, attracting greatly increased attention. Here, we review the hypotheses and evidence for different camouflage strategies used by plants and conceptualise the state of play in plant concealment under a general framework of camouflage theory. In addition, we compare the camouflage strategies used by plants and animals, outline key factors promoting and constraining the evolution of concealment, and highlight the evolutionary and ecological implications of plant camouflage. Ultimately, we show how plant camouflage exhibits many commonalities with animals and how this understudied parallel phenomenon can inform key questions in ecology and evolution.}, } @article {pmid29935935, year = {2018}, author = {Boyer, DM and Maiolino, SA and Holroyd, PA and Morse, PE and Bloch, JI}, title = {Oldest evidence for grooming claws in euprimates.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {1-22}, doi = {10.1016/j.jhevol.2018.03.010}, pmid = {29935935}, issn = {1095-8606}, abstract = {Euprimates are unusual among mammals in having fingers and toes with flat nails. While it seems clear that the ancestral stock from which euprimates evolved had claw-bearing digits, the available fossil record has not yet contributed a detailed understanding of the transition from claws to nails. This study helps clarify the evolutionary history of the second pedal digit with fossils representing the distal phalanx of digit two (dpII), and has broader implications for other digits. Among extant primates, the keratinized structure on the pedal dpII widely varies in form. Extant strepsirrhines and tarsiers have narrow, distally tapering, dorsally inclined nails (termed a 'grooming claws' for their use in autogrooming), while extant anthropoids have more typical nails that are wider and lack distal tapering or dorsal inclination. At least two fossil primate species thought to be stem members of the Strepsirrhini appear to have had grooming claws, yet reconstructions of the ancestral euprimate condition based on direct evidence from the fossil record are ambiguous due to inadequate fossil evidence for the earliest haplorhines. Seven recently discovered, isolated distal phalanges from four early Eocene localities in Wyoming (USA) closely resemble those of the pedal dpII in extant prosimians. On the basis of faunal associations, size, and morphology, these specimens are recognized as the grooming phalanges of five genera of haplorhine primates, including one of the oldest known euprimates (∼56 Ma), Teilhardina brandti. Both the phylogenetic distribution and antiquity of primate grooming phalanges now strongly suggest that ancestral euprimates had grooming claws, that these structures were modified from a primitive claw rather than a flat nail, and that the evolutionary loss of 'grooming claws' represents an apomorphy for crown anthropoids.}, } @article {pmid29935540, year = {2018}, author = {Pandit, RJ and Hinsu, AT and Patel, NV and Koringa, PG and Jakhesara, SJ and Thakkar, JR and Shah, TM and Limon, G and Psifidi, A and Guitian, J and Hume, DA and Tomley, FM and Rank, DN and Raman, M and Tirumurugaan, KG and Blake, DP and Joshi, CG}, title = {Microbial diversity and community composition of caecal microbiota in commercial and indigenous Indian chickens determined using 16s rDNA amplicon sequencing.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {115}, pmid = {29935540}, issn = {2049-2618}, support = {BB/L00478X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Bacteria/*classification/*genetics/isolation & purification ; Base Sequence ; Biodiversity ; Cecum/*microbiology ; Chickens/*microbiology ; Gastrointestinal Microbiome/*genetics ; Geography ; India ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The caecal microbiota plays a key role in chicken health and performance, influencing digestion and absorption of nutrients, and contributing to defence against colonisation by invading pathogens. Measures of productivity and resistance to pathogen colonisation are directly influenced by chicken genotype, but host driven variation in microbiome structure is also likely to exert a considerable indirect influence.

METHODS: Here, we define the caecal microbiome of indigenous Indian Aseel and Kadaknath chicken breeds and compare them with the global commercial broiler Cobb400 and Ross 308 lines using 16S rDNA V3-V4 hypervariable amplicon sequencing.

RESULTS: Each caecal microbiome was dominated by the genera Bacteroides, unclassified bacteria, unclassified Clostridiales, Clostridium, Alistipes, Faecalibacterium, Eubacterium and Blautia. Geographic location (a measure recognised to include variation in environmental and climatic factors, but also likely to feature varied management practices) and chicken line/breed were both found to exert significant impacts (p < 0.05) on caecal microbiome composition. Linear discriminant analysis effect size (LEfSe) revealed 42 breed-specific biomarkers in the chicken lines reared under controlled conditions at two different locations.

CONCLUSION: Chicken breed-specific variation in bacterial occurrence, correlation between genera and clustering of operational taxonomic units indicate scope for quantitative genetic analysis and the possibility of selective breeding of chickens for defined enteric microbiota.}, } @article {pmid29935536, year = {2018}, author = {Toju, H and Tanabe, AS and Sato, H}, title = {Network hubs in root-associated fungal metacommunities.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {116}, pmid = {29935536}, issn = {2049-2618}, mesh = {Base Sequence ; Biodiversity ; DNA, Fungal/genetics ; Endophytes/*classification/genetics/isolation & purification ; Forests ; Fungi/*classification/genetics/isolation & purification ; Host Specificity ; Japan ; Microbiota/genetics ; Mycorrhizae/physiology ; Plant Roots/*microbiology ; Plants/*microbiology ; Sequence Analysis, DNA ; Soil Microbiology ; }, abstract = {BACKGROUND: Although a number of recent studies have uncovered remarkable diversity of microbes associated with plants, understanding and managing dynamics of plant microbiomes remain major scientific challenges. In this respect, network analytical methods have provided a basis for exploring "hub" microbial species, which potentially organize community-scale processes of plant-microbe interactions.

METHODS: By compiling Illumina sequencing data of root-associated fungi in eight forest ecosystems across the Japanese Archipelago, we explored hubs within "metacommunity-scale" networks of plant-fungus associations. In total, the metadata included 8080 fungal operational taxonomic units (OTUs) detected from 227 local populations of 150 plant species/taxa.

RESULTS: Few fungal OTUs were common across all the eight forests. However, in each of the metacommunity-scale networks representing northern four localities or southern four localities, diverse mycorrhizal, endophytic, and pathogenic fungi were classified as "metacommunity hubs," which were detected from diverse host plant taxa throughout a climatic region. Specifically, Mortierella (Mortierellales), Cladophialophora (Chaetothyriales), Ilyonectria (Hypocreales), Pezicula (Helotiales), and Cadophora (incertae sedis) had broad geographic and host ranges across the northern (cool-temperate) region, while Saitozyma/Cryptococcus (Tremellales/Trichosporonales) and Mortierella as well as some arbuscular mycorrhizal fungi were placed at the central positions of the metacommunity-scale network representing warm-temperate and subtropical forests in southern Japan.

CONCLUSIONS: The network theoretical framework presented in this study will help us explore prospective fungi and bacteria, which have high potentials for agricultural application to diverse plant species within each climatic region. As some of those fungal taxa with broad geographic and host ranges have been known to promote the survival and growth of host plants, further studies elucidating their functional roles are awaited.}, } @article {pmid29935301, year = {2018}, author = {Melo, BF and Sidlauskas, BL and Hoekzema, K and Vari, RP and Dillman, CB and Oliveira, C}, title = {Molecular phylogenetics of Neotropical detritivorous fishes of the family Curimatidae (Teleostei: Characiformes).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {800-812}, doi = {10.1016/j.ympev.2018.06.027}, pmid = {29935301}, issn = {1095-9513}, abstract = {Curimatidae, the fourth largest family of detritivorous Neotropical characiform fishes, encompasses eight extant genera and over 110 species dwelling in diverse freshwater habitats from Costa Rica to Argentina. Extensive phylogenetic analyses of soft anatomy and osteology provided evidence for intergeneric and most interspecific relationships, and formed the basis of curimatid taxonomy for nearly 40 years. However, that morphological phylogeny demonstrated incomplete phylogenetic resolution at various scales and has never been tested with extensive molecular data. Herein, we infer molecular phylogenies spanning ∼70% of the known species diversity using three nuclear and three mitochondrial loci. Topologies from concatenated likelihood and Bayesian analyses and coalescent Bayesian species trees agree broadly with each other, and with the prior morphological hypothesis in many, but not all respects. All molecular analyses support the monophyly of Curimatidae and of six of its constituent genera, and agree on the placement of Curimatopsis as sister to all other curimatids. DNA-based intergeneric relationships differ substantially from prior morphological hypotheses by placing Curimata sister to Potamorhina and Psectrogaster sister to Pseudocurimata, rather than in a ladderized arrangement. Our results also resolve a major uncertainty in the morphological tree by revealing Cyphocharax, a genus for which no anatomical synapomorphy has ever been proposed, as a paraphyletic assemblage containing a monophyletic Steindachnerina and a polyphyletic Curimatella. Overall, the phylogeny expands substantially our understanding of the morphology, phylogenetics and evolution of the Curimatidae, and will guide future intrageneric studies by improving precision in the choice of comparative taxa.}, } @article {pmid29935300, year = {2018}, author = {Oberski, JT and Sharma, PP and Jay, KR and Coblens, MJ and Lemon, KA and Johnson, JE and Boyer, SL}, title = {A dated molecular phylogeny of mite harvestmen (Arachnida: Opiliones: Cyphophthalmi) elucidates ancient diversification dynamics in the Australian Wet Tropics.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {813-822}, doi = {10.1016/j.ympev.2018.06.029}, pmid = {29935300}, issn = {1095-9513}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Austropurcellia, a genus of dispersal-limited arachnids endemic to isolated patches of coastal rainforest in Queensland, Australia, has a remarkable biogeographic history. The genus is a member of the family Pettalidae, which has a classical temperate Gondwanan distribution; previous work has suggested that Austropurcellia is an ancient lineage, with an origin that predates Gondwanan rifting. Subsequently, this lineage has persisted through major climatic fluctuations, such as major aridification during the Miocene and contraction and fragmentation of forest habitats during the Last Glacial Maximum (LGM). In order to understand Austropurcellia's evolutionary and biogeographic history, we generated DNA sequences from both mitochondrial and nuclear loci and combined this information with previously published datasets for the globally-distributed suborder Cyphophthalmi (i.e., all mite harvestmen). We generated phylogenetic trees using maximum likelihood and Bayesian approaches to date divergences using a relaxed molecular clock. According to our estimates, the family Pettalidae diversified in the late Jurassic, in accordance with Gondwanan vicariance. Within Pettalidae, Austropurcellia split from its sister group in the early Cretaceous and began to diversify some 15 Ma later. Therefore, its presence in Australia predates continental rifting-making it one of very few hypothesized examples of Gondwanan vicariance that have withstood rigorous testing. We found a steady rate of diversification within the genus, with no evidence for a shift in rate associated with Miocene aridification. Ages of splits between species predate the Pleistocene, consistent with a "museum" model in which forest refugia acted to preserve existing lineages rather than drive speciation within the group.}, } @article {pmid29935146, year = {2018}, author = {Kokla, A and Melnyk, CW}, title = {Developing a thief: Haustoria formation in parasitic plants.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {53-59}, doi = {10.1016/j.ydbio.2018.06.013}, pmid = {29935146}, issn = {1095-564X}, mesh = {Gene Expression Regulation, Plant/genetics ; Plant Development/physiology ; Plant Proteins ; Plant Roots/*anatomy & histology/metabolism ; Plants/anatomy & histology/*parasitology ; }, abstract = {Parasitic plants are widespread pathogens that infect numerous plant species and cause devastating agricultural losses. They efficiently withdraw water, nutrients and sugars from their hosts by fusing tissues and connecting their vasculature to the host vasculature. This ability to parasitize is found in a wide range of species and has evolved at least eleven independent times, suggesting a recurring and flexible developmental strategy. Despite multiple independent origins, a common feature to parasitism is the formation of an invasive organ termed the haustorium. Parasitic plants form haustoria in their stems or roots and use this structure to penetrate host tissues and form vascular connections, often with distantly related species. This ability to join to an unrelated species is remarkable, and together with the economic importance of parasitism, there is a strong need to further understand how parasitic plants infect their hosts. Here, we discuss the developmental basis for plant parasitism, focusing on haustorial initiation, penetration and vascular formation. We also discuss future directions and outstanding questions in this emerging field.}, } @article {pmid29934881, year = {2018}, author = {Mendes, MM and da Silva, CB and Rodrigues, DBR and Rodrigues, BR and Geraldo-Martins, VR and Ferriani, VPL and Rodrigues, V and Nogueira, RD}, title = {Streptococcus mutans in Umbilical Cord Blood, Peripheral Blood, and Saliva from Healthy Mothers.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29934881}, issn = {1432-0991}, abstract = {The aims of this study were to analyze the presence of Streptococcus mutans (SM)-DNA in cord blood (CB), maternal peripheral blood (PB), and maternal saliva (SA) and compare with data collected in health surveys. Sixty-four healthy women with pregnancies to term and without complications attending for elective cesarean section in the Clinical Hospital of Ribeirao Preto, Sao Paulo were included. Samples of PB and unstimulated SA were obtained on the day of hospitalization and samples of CB were collected after the delivery section. Samples were investigated using polymerase chain reaction for the presence of SM-DNA using specific primers. The results show over 50% of the sample of PB and CB showed SM-DNA detectable. There was a positive correlation between the SM detection in PB/CB and SA (P < 0.05). Pregnant women, who reported tooth brushing more than three times a day, often showed detectable SM-DNA in PB and CB (P < 0.05). In conclusion, the majority of children can have contact with SM-DNA during the intrauterine life by the CB. SM probably transferred from salivary habitat to PB and CB. The tooth brushing can be associated to S. mutans detection in blood samples.}, } @article {pmid29934734, year = {2018}, author = {Teixeira, JR and Dias, GB and Svartman, M and Ruiz, A and Kuhn, GCS}, title = {Concurrent Duplication of Drosophila Cid and Cenp-C Genes Resulted in Accelerated Evolution and Male Germline-Biased Expression of the New Copies.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {29934734}, issn = {1432-1432}, support = {APQ-01563-14//Fundação de Amparo à Pesquisa do Estado de Minas Gerais/ ; 404620/2016-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, abstract = {Despite their essential role in the process of chromosome segregation in eukaryotes, kinetochore proteins are highly diverse across species, being lost, duplicated, created, or diversified during evolution. Based on comparative genomics, the duplication of the inner kinetochore proteins CenH3 and Cenp-C, which are interdependent in their roles of establishing centromere identity and function, can be said to be rare in animals. Surprisingly, the Drosophila CenH3 homolog Cid underwent four independent duplication events during evolution. Particularly interesting are the highly diverged Cid1 and Cid5 paralogs of the Drosophila subgenus, which are probably present in over one thousand species. Given that CenH3 and Cenp-C likely co-evolve as a functional unit, we investigated the molecular evolution of Cenp-C in species of Drosophila. We report yet another Cid duplication (leading to Cid6) within the Drosophila subgenus and show that not only Cid, but also Cenp-C is duplicated in the entire subgenus. The Cenp-C paralogs, which we named Cenp-C1 and Cenp-C2, are highly divergent. Both Cenp-C1 and Cenp-C2 retain key motifs involved in centromere localization and function, while some functional motifs are conserved in an alternate manner between the paralogs. Interestingly, both Cid5 and Cenp-C2 are male germline-biased and evolved adaptively. However, it is currently unclear if the paralogs subfunctionalized or if the new copies acquired a new function. Our findings point towards a specific inner kinetochore composition in a specific context (i.e., spermatogenesis), which could prove valuable for the understanding of how the extensive kinetochore diversity is related to essential cellular functions.}, } @article {pmid29934629, year = {2018}, author = {Clyde, D}, title = {Prospecting for pluripotency.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {471}, doi = {10.1038/s41576-018-0030-1}, pmid = {29934629}, issn = {1471-0064}, } @article {pmid29934592, year = {2018}, author = {He, F and Bhoobalan-Chitty, Y and Van, LB and Kjeldsen, AL and Dedola, M and Makarova, KS and Koonin, EV and Brodersen, DE and Peng, X}, title = {Publisher Correction: Anti-CRISPR proteins encoded by archaeal lytic viruses inhibit subtype I-D immunity.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1076}, doi = {10.1038/s41564-018-0184-9}, pmid = {29934592}, issn = {2058-5276}, abstract = {In the original version of this Article, molecular weight markers in Figs 1c, 2c,d and 4d were displaced during the production process, so that they were not correctly aligned with the corresponding bands. In addition, in Fig. 4c, molecular masses given for three different elution volumes were displaced so that they appeared to the left of the correct positions. These errors have now been corrected.}, } @article {pmid29934402, year = {2018}, author = {Hardigan, MA and Laimbeer, FPE and Hamilton, JP and Vaillancourt, B and Douches, DS and Farré, EM and Veilleux, RE and Buell, CR}, title = {Reply to Huang et al.: Avoiding "one-size-fits-all" approaches to variant discovery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6394-E6395}, pmid = {29934402}, issn = {1091-6490}, } @article {pmid29934401, year = {2018}, author = {Jonik-Nowak, B and Menneteau, T and Fesquet, D and Baldin, V and Bonne-Andrea, C and Méchali, F and Fabre, B and Boisguerin, P and de Rossi, S and Henriquet, C and Pugnière, M and Ducoux-Petit, M and Burlet-Schiltz, O and Lamond, AI and Fort, P and Boulon, S and Bousquet, MP and Coux, O}, title = {PIP30/FAM192A is a novel regulator of the nuclear proteasome activator PA28γ.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6477-E6486}, pmid = {29934401}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 097945/B/11/Z//Wellcome Trust/United Kingdom ; 108058/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Autoantigens/genetics/*metabolism ; Cell Nucleus/genetics/*metabolism ; HeLa Cells ; Humans ; Nuclear Proteins/genetics/metabolism ; Proteasome Endopeptidase Complex/genetics/*metabolism ; Protein Binding ; Protein Domains ; Proteins/genetics/*metabolism ; }, abstract = {PA28γ is a nuclear activator of the 20S proteasome involved in the regulation of several essential cellular processes, such as cell proliferation, apoptosis, nuclear dynamics, and cellular stress response. Unlike the 19S regulator of the proteasome, which specifically recognizes ubiquitylated proteins, PA28γ promotes the degradation of several substrates by the proteasome in an ATP- and ubiquitin-independent manner. However, its exact mechanisms of action are unclear and likely involve additional partners that remain to be identified. Here we report the identification of a cofactor of PA28γ, PIP30/FAM192A. PIP30 binds directly and specifically via its C-terminal end and in an interaction stabilized by casein kinase 2 phosphorylation to both free and 20S proteasome-associated PA28γ. Its recruitment to proteasome-containing complexes depends on PA28γ and its expression increases the association of PA28γ with the 20S proteasome in cells. Further dissection of its possible roles shows that PIP30 alters PA28γ-dependent activation of peptide degradation by the 20S proteasome in vitro and negatively controls in cells the presence of PA28γ in Cajal bodies by inhibition of its association with the key Cajal body component coilin. Taken together, our data show that PIP30 deeply affects PA28γ interactions with cellular proteins, including the 20S proteasome, demonstrating that it is an important regulator of PA28γ in cells and thus a new player in the control of the multiple functions of the proteasome within the nucleus.}, } @article {pmid29934400, year = {2018}, author = {Naud, R and Sprekeler, H}, title = {Sparse bursts optimize information transmission in a multiplexed neural code.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6329-E6338}, pmid = {29934400}, issn = {1091-6490}, mesh = {Animals ; Cerebral Cortex/cytology/*physiology ; Humans ; *Models, Neurological ; Neurons/cytology/*physiology ; Synaptic Transmission/*physiology ; }, abstract = {Many cortical neurons combine the information ascending and descending the cortical hierarchy. In the classical view, this information is combined nonlinearly to give rise to a single firing-rate output, which collapses all input streams into one. We analyze the extent to which neurons can simultaneously represent multiple input streams by using a code that distinguishes spike timing patterns at the level of a neural ensemble. Using computational simulations constrained by experimental data, we show that cortical neurons are well suited to generate such multiplexing. Interestingly, this neural code maximizes information for short and sparse bursts, a regime consistent with in vivo recordings. Neurons can also demultiplex this information, using specific connectivity patterns. The anatomy of the adult mammalian cortex suggests that these connectivity patterns are used by the nervous system to maintain sparse bursting and optimal multiplexing. Contrary to firing-rate coding, our findings indicate that the physiology and anatomy of the cortex may be interpreted as optimizing the transmission of multiple independent signals to different targets.}, } @article {pmid29934399, year = {2018}, author = {Huang, B and Spooner, DM and Liang, Q}, title = {Genome diversity of the potato.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {E6392-E6393}, pmid = {29934399}, issn = {1091-6490}, mesh = {*Genetic Variation ; Genome, Plant ; Phylogeny ; Solanum tuberosum/*genetics ; }, } @article {pmid29934102, year = {2018}, author = {Hassett, MR and Roepe, PD}, title = {PIK-ing New Malaria Chemotherapy.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {925-927}, doi = {10.1016/j.pt.2018.06.003}, pmid = {29934102}, issn = {1471-5007}, abstract = {Phosphatidylinositol (PI) kinases (PIKs) regulate cell proliferation, survival, membrane trafficking, and other processes. PIK classes are distinguished by substrate preference and their distinct phosphorylated PI products. Recently two Plasmodium falciparum PIKs (PfPIKs) have been recognized as attractive new drug targets. Here we briefly summarize PIK biochemistry and recent progress with PfPIKs.}, } @article {pmid29933925, year = {2018}, author = {Douam, F and Ploss, A}, title = {Yellow Fever Virus: Knowledge Gaps Impeding the Fight Against an Old Foe.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {913-928}, doi = {10.1016/j.tim.2018.05.012}, pmid = {29933925}, issn = {1878-4380}, support = {R01 AI107301/AI/NIAID NIH HHS/United States ; R21 AI106000/AI/NIAID NIH HHS/United States ; R21 AI117213/AI/NIAID NIH HHS/United States ; }, abstract = {Yellow fever (YF) was one of the most dangerous infectious diseases of the 18th and 19th centuries, resulting in mass casualties in Africa and the Americas. The etiologic agent is yellow fever virus (YFV), and its live-attenuated form, YFV-17D, remains one of the most potent vaccines ever developed. During the first half of the 20th century, vaccination combined with mosquito control eradicated YFV transmission in urban areas. However, the recent 2016-2018 outbreaks in areas with historically low or no YFV activity have raised serious concerns for an estimated 400-500 million unvaccinated people who now live in at-risk areas. Once a forgotten disease, we highlight here that YF still represents a very real threat to human health and economies. As many gaps remain in our understanding of how YFV interacts with the human host and causes disease, there is an urgent need to address these knowledge gaps and propel YFV research forward.}, } @article {pmid29933763, year = {2018}, author = {Zhang, Y and Peng, X and Liu, Y and Li, Y and Luo, Y and Wang, X and Tang, H}, title = {Evaluation of suitable reference genes for qRT-PCR normalization in strawberry (Fragaria × ananassa) under different experimental conditions.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {8}, pmid = {29933763}, issn = {1471-2199}, mesh = {Algorithms ; Fragaria/*genetics/growth & development ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Plant Proteins/*genetics ; Real-Time Polymerase Chain Reaction/*standards ; Reference Standards ; }, abstract = {BACKGROUND: Strawberry has received much attention due to its nutritional value, unique flavor, and attractive appearance. The availability of the whole genome sequence and multiple transcriptome databases allows the great possibility to explore gene functions, comprehensively. Gene expression profiles of a target gene can provide clues towards the understanding of its biological function. Quantitative real-time PCR (qRT-PCR) is a preferred method for rapid quantification of gene expression. The accuracy of the results obtained by this method requires the reference genes with consistently stable expression to normalize its data.

RESULTS: In present study, the expression stability of seven candidate reference genes in diverse sample subsets of different tissues and fruit developmental stages, and plant subjected to light quality and low temperature treatments was evaluated using three statistical algorithms, geNorm, NormFinder, and BestKeeper. Our data indicated that the expression stability of reference genes varied under different experimental conditions. Overall, DBP, HISTH4, ACTIN1 and GAPDH expressed much more stably. PIRUV, ACTIN2 and 18S were not recommended for normalization in given experimental conditions due to low stability. In addition, the relative expression pattern of HY5 (ELONGATED HYPOCOTYL5) was conducted to further confirm the reliability of the reference genes, which demonstrated the correct adoption of reference genes was of great importance in qRT-PCR analysis.

CONCLUSIONS: Expression stability of reference genes from strawberry varied across selected experimental conditions. Systematic validation of reference genes prior to calculation of target gene expression level should be done to improve the accuracy and consistency of qRT-PCR analysis.}, } @article {pmid29933435, year = {2018}, author = {Akob, DM and Sutton, JM and Fierst, JL and Haase, KB and Baesman, S and Luther, GW and Miller, LG and Oremland, RS}, title = {Acetylenotrophy: a hidden but ubiquitous microbial metabolism?.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy103}, pmid = {29933435}, issn = {1574-6941}, abstract = {Acetylene (IUPAC name: ethyne) is a colorless, gaseous hydrocarbon, composed of two triple bonded carbon atoms attached to hydrogens (C2H2). When microbiologists and biogeochemists think of acetylene, they immediately think of its use as an inhibitory compound of certain microbial processes and a tracer for nitrogen fixation. However, what is less widely known is that anaerobic and aerobic microorganisms can degrade acetylene, using it as a sole carbon and energy source and providing the basis of a microbial food web. Here, we review what is known about acetylene degrading organisms and introduce the term 'acetylenotrophs' to refer to the microorganisms that carry out this metabolic pathway. In addition, we review the known environmental sources of acetylene and postulate the presence of an hidden acetylene cycle. The abundance of bacteria capable of using acetylene and other alkynes as an energy and carbon source suggests that there are energy cycles present in the environment that are driven by acetylene and alkyne production and consumption that are isolated from atmospheric exchange. Acetylenotrophs may have developed to leverage the relatively high concentrations of acetylene in the pre-Cambrian atmosphere, evolving later to survive in specialized niches where acetylene and other alkynes were produced.}, } @article {pmid29933039, year = {2018}, author = {Brock, JR and Dönmez, AA and Beilstein, MA and Olsen, KM}, title = {Phylogenetics of Camelina Crantz. (Brassicaceae) and insights on the origin of gold-of-pleasure (Camelina sativa).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {834-842}, doi = {10.1016/j.ympev.2018.06.031}, pmid = {29933039}, issn = {1095-9513}, support = {52006942/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Camelina sativa (false flax or gold-of-pleasure) is an Old World oilseed crop that fell out of use in the mid 20th Century but has recently gained renewed interest as a biofuel source. The crop is hexaploid, and its relationship to its diploid and polyploid congeners has remained unresolved. Using 54 accessions representing five species sampled across Camelina's center of diversity in Turkey and the Caucasus, we performed phylogenetic and genetic diversity analyses using RADseq genotyping and ITS sequencing. Flow cytometry was performed to assess relationships between genome size and phylogenetic groupings. Accessions fell into distinct, highly-supported clades that accord with named species, indicating that morphological characters can reliably distinguish members of the genus. A phylogenetically distinct lineage from Turkey may represent a currently unrecognized diploid species. In most analyses, C. sativa accessions nest within those of C. microcarpa, suggesting that the crop is descended from this wild hexaploid species. This inference is further supported by their similar genome size, and by lower genetic diversity in C. sativa, which is consistent with a domestication bottleneck. These analyses provide the first definitive phylogeny of C. sativa and its wild relatives, and they point to C. microcarpa as the crop's wild ancestor.}, } @article {pmid29932896, year = {2018}, author = {Betters, E and Charney, RM and Garcia-Castro, MI}, title = {Early specification and development of rabbit neural crest cells.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.06.012}, pmid = {29932896}, issn = {1095-564X}, support = {R01 DE017914/DE/NIDCR NIH HHS/United States ; }, abstract = {The phenomenal migratory and differentiation capacity of neural crest cells has been well established across model organisms. While the earliest stages of neural crest development have been investigated in non-mammalian model systems such as Xenopus and Aves, the early specification of this cell population has not been evaluated in mammalian embryos, of which the murine model is the most prevalent. Towards a more comprehensive understanding of mammalian neural crest formation and human comparative studies, we have used the rabbit as a mammalian system for the study of early neural crest specification and development. We examine the expression profile of well-characterized neural crest markers in rabbit embryos across developmental time from early gastrula to later neurula stages, and provide a comparison to markers of migratory neural crest in the chick. Importantly, we apply explant specification assays to address the pivotal question of mammalian neural crest ontogeny, and provide the first evidence that a specified population of neural crest cells exists in the rabbit gastrula prior to the overt expression of neural crest markers. Finally, we demonstrate that FGF signaling is necessary for early rabbit neural crest formation, as SU5402 treatment strongly represses neural crest marker expression in explant assays. This study pioneers the rabbit as a model for neural crest development, and provides the first demonstration of mammalian neural crest specification and the requirement of FGF signaling in this process.}, } @article {pmid29932895, year = {2018}, author = {Jin, S and O, J and Stellabotte, F and Choe, CP}, title = {Foxi1 promotes late-stage pharyngeal pouch morphogenesis through ectodermal Wnt4a activation.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {12-18}, doi = {10.1016/j.ydbio.2018.06.011}, pmid = {29932895}, issn = {1095-564X}, mesh = {Animals ; Ectoderm/*embryology ; Fibroblast Growth Factors/genetics/metabolism ; Forkhead Transcription Factors/genetics/*metabolism ; Gene Expression Regulation, Developmental/*physiology ; Mutation ; Organogenesis/*physiology ; Pharynx/*embryology ; Wnt Signaling Pathway/physiology ; Wnt4 Protein/*biosynthesis/genetics ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {The pharyngeal pouches are a series of epithelial outgrowths of the foregut endoderm. Pharyngeal pouches segment precursors of the vertebrate face into pharyngeal arches and pattern the facial skeleton. These pouches fail to develop normally in zebrafish foxi1 mutants, yet the role Foxi1 plays in pouch development remains to be determined. Here we show that ectodermal Foxi1 acts downstream of Fgf8a during the late stage of pouch development to promote rearrangement of pouch-forming cells into bilayers. During this phase, foxi1 and wnt4a are coexpressed in the facial ectoderm and their expression is expanded in fgf8a mutants. foxi1 expression is unaffected in wnt4a mutants; conversely, ectodermal wnt4a expression is abolished in foxi1 mutants. Consistent with this, foxi1 mutant pouch and facial skeletal defects resemble those of wnt4a mutants. These findings suggest that ectodermal Foxi1 mediates late-stage pouch morphogenesis through wnt4a expression. We therefore propose that Fox1 activation of Wnt4a in the ectoderm signals the epithelial stabilization of pouch-forming cells during late-stage of pouch morphogenesis.}, } @article {pmid29932394, year = {2018}, author = {La Mura, A and Arahal, DR and Pujalte, MJ}, title = {Roseivivax atlanticus (Li, Lai, Liu, Sun and Shao, 2015) is a later heterotypic synonym of Roseivivax marinus (Dai, Shi, Gao, Liu and Zhang, 2014).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2650-2652}, doi = {10.1099/ijsem.0.002893}, pmid = {29932394}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Nucleic Acid Hybridization ; *Phylogeny ; Rhodobacteraceae/*classification ; Sequence Analysis, DNA ; }, abstract = {The genomes of the type strains of Roseivivax atlanticusand Roseivivax marinus(Rhodobacteraceae, Alphaproteobacteria), were analysed to determine their respective Average Nucleotide Identity (ANI) and in silico DNA-DNA hybridization (DDH) values. These species were proposed and effectively published relatively closely in time (February and August 2014, respectively) and so not taking account of the other. The intergenomic relatedness between both type strains, 97.0-97.4 % ANI and 82.8 % in silico DDH, confirm that they represent members of the same genomic species. This conclusion is also supported at the phenotypic level. Since the nameRoseovarius marinuswas validly published earlier, R. atlanticus (Validation List 161, IJSEM 65, 1-4. 2015) should be considered a later heterotypic synonym of R. marinus(Dai, Shi, Gao, Liu and Zhang, 2014), in application of the priority rule.}, } @article {pmid29932390, year = {2018}, author = {Carvalho, C and Tomás, A and Libkind, D and Imanishi, Y and Sampaio, JP}, title = {Zygotorulaspora chibaensis sp. nov. and Zygotorulaspora danielsina sp. nov., novel ascomycetous yeast species from tree bark and soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2633-2637}, doi = {10.1099/ijsem.0.002889}, pmid = {29932390}, issn = {1466-5034}, mesh = {DNA, Fungal/genetics ; *Forests ; Japan ; Mycological Typing Techniques ; New Zealand ; *Phylogeny ; Plant Bark/*microbiology ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil Microbiology ; Xylose ; }, abstract = {Multiple isolates belonging to the ascomycetous genus Zygotorulaspora were obtained from forest soils and tree bark in Shiba Prefecture in Japan, and Lake Daniels, Lewis Pass, in New Zealand. Phylogenetic analyses employing combined sequences of the D1/D2 domain and ITS region support the recognition of two new species: Zygotorulaspora chibaensis sp. nov. (type strain PYCC 6970T=CBS 15364T) and Zygotorulaspora danielsina sp. nov. (type strain PYCC 6984T=CBS 15365T). Both species are able to grow on d-xylose and l-arabinose and at 35 °C, unlike Zygotorulaspora florentina and Zygotorulaspora mrakii, the other two species in the genus.}, } @article {pmid29932388, year = {2018}, author = {Baek, K and Chung, EJ and Choi, GG and Kim, MK and Lim, S and Choi, A}, title = {Deinococcus koreensis sp. nov., a gamma radiation-resistant bacterium isolated from river water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2545-2550}, doi = {10.1099/ijsem.0.002872}, pmid = {29932388}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Deinococcus/*classification/isolation & purification/radiation effects ; Fatty Acids/chemistry ; *Gamma Rays ; Glycolipids/chemistry ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Radiation Tolerance ; Republic of Korea ; Rivers/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A gamma radiation-resistant, Gram-stain-negative, rod-shaped bacterial strain, designated SJW1-2T, was isolated from freshwater samples collected from the Seomjin River, Republic of Korea. The 16S rRNA gene sequence analyses showed that strain SJW1-2T was most closely related to Deinococcus metalli 1PNM-19T (94.3 % sequence similarity) and formed a robust phylogenetic clade with other species of the genus Deinococcus. The optimum growth pH and temperature for the isolate were pH 7.0-7.5 and 25 °C, respectively. Strain SJW1-2T exhibited high resistance to gamma radiation. The predominant respiratory quinone was MK-8. The polar lipid profile consisted of different unidentified glycolipids, two unidentified lipids, two unidentified phospholipids and an unidentified phosphoglycolipid. The major peptidoglycan amino acids were alanine, d-glutamic acid, glycine and l-ornithine. The predominant fatty acids (>10 %) were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (25.2 %) and C16 : 0 (21.2 %), and the DNA G+C content was 69.5 mol%. On the basis of phenotypic, genotypic and phylogenetic analyses, strain SJW1-2T (=KACC 19332T=NBRC 112908T) represents a novel species of the genus Deinococcus, for which the name Deinococcus koreensis sp. nov. is proposed.}, } @article {pmid29932387, year = {2018}, author = {Liu, SQ and Sun, QL and Sun, YY and Yu, C and Sun, L}, title = {Muricauda iocasae sp. nov., isolated from deep sea sediment of the South China Sea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2538-2544}, doi = {10.1099/ijsem.0.002870}, pmid = {29932387}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/microbiology ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {In this study, we reported a novel yellow-pigmented, Gram-stain-negative bacterium with appendages, designated as strain L2T, isolated from the South China Sea. Growth of strain L2T occurred at 22-40 °C (optimum, 37 °C), pH 6.0-10.0 (pH 7.0) and with 0-8 % (w/v) NaCl (2 %). Phylogenetic analysis based on its 16S rRNA gene sequence indicated that strain L2T belonged to the genus Muricauda. The close phylogenetic neighbours of strain L2T were Muricauda marina H19-56T, Muricauda ruestringensis B1T, Muricauda antarctica Ar-22T, Muricauda taeanensis 105T and Muricauda flavescens SW-62T (96.4 %, 95.9 %, 95.9 %, 95.8 % and 94.5 % identities, respectively). The genomic DNA G+C content of strain L2T was 51.3±4.6 mol%. Theg major isoprenoid quinone was MK-6 (100.0 %). The polar lipids contained phosphatidylethanolamine and two unidentified lipids. The major fatty acids (>10 % of total fatty acids) were iso-C17 : 0 3-OH (30.3 %), iso-C15 : 1 G (20.6 %) and iso-C15 : 0 (17.6 %). Phylogenetic, physiological, biochemical and morphological analysis suggested that this strain represents a novel species of genus Muricauda, and the name Muricauda iocasae sp. nov. is proposed with the type species L2T (=CCTCC AB 2017193 T=KCTC 62196T).}, } @article {pmid29932385, year = {2018}, author = {Kämpfer, P and Glaeser, SP and Packroff, G and Behringer, K and Exner, M and Chakraborty, T and Schmithausen, RM and Doijad, S}, title = {Lelliottia aquatilis sp. nov., isolated from drinking water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2454-2461}, doi = {10.1099/ijsem.0.002854}, pmid = {29932385}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Drinking Water/*microbiology ; Enterobacteriaceae/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Genes, Bacterial ; Germany ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Five beige-pigmented, oxidase-negative bacterial isolates, 6331-17T, 6332-17, 6333-17, 6334-17 and 9827-07, isolated either from a drinking water storage reservoir or drinking water in 2006 and 2017 in Germany, were examined in detail applying by a polyphasic taxonomic approach. Cells of the isolates were rod-shaped and Gram-stain-negative. Comparison of the 16S rRNA gene sequences of these five isolates showed highest sequence similarities to Lelliottia amnigena (99.98 %) and Lelliottia nimipressuralis (99.99 %). Multilocus sequence analyses based on concatenated partial rpoB, gyrB, infB and atpD sequences confirmed the clustering of these isolates with Lelliottia species, but also revealed a clear distinction to the closest related type strains. Analysis of the genome sequences of these isolates indicated >70 % in silico DNA-DNA hybridization and high average nucleotide identities between strains. Nevertheless, they showed only <70 and <95 % similarity to the type strains of these two Lelliottia species. The fatty acid profiles of these isolates were very similar and consisted of the major fatty acids C16:0, C17 : 0cyclo, C15 : 0iso 2-OH/C16 : 1ω7c and C18 : 1ω7c. In addition, physiological/biochemical tests revealed high phenotypic similarity to each other. These cumulative data indicate that these isolates represent a novel Lelliottia species, for which the name Lelliottia aquatilis sp. nov. is proposed, with strain 6331-17T (=CCM 8846T=CIP 111609T=LMG 30560T) as the type strain.}, } @article {pmid29932347, year = {2018}, author = {Kim, K}, title = {The Epigenome, Cell Cycle, and Development in Toxoplasma.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {479-499}, doi = {10.1146/annurev-micro-090817-062741}, pmid = {29932347}, issn = {1545-3251}, abstract = {Toxoplasma gondii is a common veterinary and human pathogen that persists as latent bradyzoite forms within infected hosts. The ability of the parasite to interconvert between tachyzoite and bradyzoite is key for pathogenesis of toxoplasmosis, particularly in immunocompromised individuals. The transition between tachyzoites and bradyzoites is epigenetically regulated and coupled to the cell cycle. Recent epigenomic studies have begun to elucidate the chromatin states associated with developmental switches in T. gondii. Evidence is also emerging that AP2 transcription factors both activate and repress the bradyzoite developmental program. Further studies are needed to understand the mechanisms by which T. gondii transduces environmental signals to coordinate the epigenetic and transcriptional machinery that are responsible for tachyzoite-bradyzoite interconversion.}, } @article {pmid29932170, year = {2018}, author = {Thompson, J and Undie, CC and Amin, A and Johnson, BR and Khosla, R and Ouedraogo, L and Nkurunziza, T and Rich, S and Westley, E and Garcia, M and Birungi, H and Askew, I}, title = {Correction to: Harmonizing national abortion and pregnancy prevention laws and policies for sexual violence survivors with the Maputo Protocol: proceedings of a 2016 regional technical meeting in sub-Saharan Africa.}, journal = {BMC proceedings}, volume = {12}, number = {}, pages = {7}, doi = {10.1186/s12919-018-0103-3}, pmid = {29932170}, issn = {1753-6561}, abstract = {[This corrects the article DOI: 10.1186/s12919-018-0101-5.].}, } @article {pmid29931833, year = {2018}, author = {Wanninger, A and Wollesen, T}, title = {The evolution of molluscs.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12439}, pmid = {29931833}, issn = {1469-185X}, abstract = {Molluscs are extremely diverse invertebrate animals with a rich fossil record, highly divergent life cycles, and considerable economical and ecological importance. Key representatives include worm-like aplacophorans, armoured groups (e.g. polyplacophorans, gastropods, bivalves) and the highly complex cephalopods. Molluscan origins and evolution of their different phenotypes have largely remained unresolved, but significant progress has been made over recent years. Phylogenomic studies revealed a dichotomy of the phylum, resulting in Aculifera (shell-less aplacophorans and multi-shelled polyplacophorans) and Conchifera (all other, primarily uni-shelled groups). This challenged traditional hypotheses that proposed that molluscs gradually evolved complex phenotypes from simple, worm-like animals, a view that is corroborated by developmental studies that showed that aplacophorans are secondarily simplified. Gene expression data indicate that key regulators involved in anterior-posterior patterning (the homeobox-containing Hox genes) lost this function and were co-opted into the evolution of taxon-specific novelties in conchiferans. While the bone morphogenetic protein (BMP)/decapentaplegic (Dpp) signalling pathway, that mediates dorso-ventral axis formation, and molecular components that establish chirality appear to be more conserved between molluscs and other metazoans, variations from the common scheme occur within molluscan sublineages. The deviation of various molluscs from developmental pathways that otherwise appear widely conserved among metazoans provides novel hypotheses on molluscan evolution that can be tested with genome editing tools such as the CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/clustered regularly interspaced short palindromic repeats-associated protein9) system.}, } @article {pmid29931384, year = {2018}, author = {Jang, WJ and Lee, JM and Kim, YR and Hasan, MT and Kong, IS}, title = {Complete Genome Sequence of Bacillus sp. SJ-10 (KCCM 90078) Producing 400-kDa Poly-γ-glutamic Acid.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29931384}, issn = {1432-0991}, abstract = {Bacillus sp. SJ-10 (KCCM 90078, JCM 15709) is a halotolerant bacterium isolated from a traditional Korean food, i.e., salt-fermented fish (jeotgal). The bacterium can survive and engage in metabolism at high salt concentrations. Here, we reported complete genome sequence of Bacillus sp. SJ-10, which has a single circular chromosome of 4,041,649 base pairs with a guanine-cytosine content of 46.39%. Bacillus sp. SJ-10 encodes a subunit of poly-γ-glutamic acid (γ-PGA) with a molecular weight of approximately 400 kDa, which contains four γ-PGA synthases (pgsB, pgsC, pgsAA and pgsE) and one γ-PGA-releasing gene (pgsS). This bacterium also able to produce salt-stable enzymes such as protease, β-glucosidase, and β-1,3-1,4-glucanase. This affords significant insights into strategies employed by halotolerant bacteria to survive at high salt concentrations. The sequence contains information on secondary metabolites biosynthetic gene cluster, and most importantly enzymes produced by the bacterium may be valuable with respect to food, beverage, detergent, animal feed, and certain commercial contexts.}, } @article {pmid29931341, year = {2018}, author = {Landa, M and Blain, S and Harmand, J and Monchy, S and Rapaport, A and Obernosterer, I}, title = {Major changes in the composition of a Southern Ocean bacterial community in response to diatom-derived dissolved organic matter.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy067}, pmid = {29931341}, issn = {1574-6941}, } @article {pmid29931311, year = {2018}, author = {Diepeveen, ET and Gehrmann, T and Pourquié, V and Abeel, T and Laan, L}, title = {Patterns of Conservation and Diversification in the Fungal Polarization Network.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1765-1782}, pmid = {29931311}, issn = {1759-6653}, mesh = {Cell Polarity ; *Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; Fungi/*cytology/*genetics/metabolism ; Genes, Fungal ; Genome, Fungal ; *Phylogeny ; *Protein Interaction Maps ; Saccharomyces cerevisiae/cytology/genetics/metabolism ; }, abstract = {The combined actions of proteins in networks underlie all fundamental cellular functions. Deeper insights into the dynamics of network composition across species and their functional consequences are crucial to fully understand protein network evolution. Large-scale comparative studies with high phylogenetic resolution are now feasible through the recent rise in available genomic data sets of both model and nonmodel species. Here, we focus on the polarity network, which is universally essential for cell proliferation and studied in great detail in the model organism, Saccharomyces cerevisiae. We examine 42 proteins, directly related to cell polarization, across 298 fungal strains/species to determine the composition of the network and patterns of conservation and diversification. We observe strong protein conservation for a group of 23 core proteins: >95% of all examined strains/species possess at least 14 of these core proteins, albeit in varying compositions, and non of the individual core proteins is 100% conserved. We find high levels of variation in prevalence and sequence identity in the remaining 19 proteins, resulting in distinct lineage-specific compositions of the network in the majority of strains/species. We show that the observed diversification in network composition correlates with lineage, lifestyle, and genetic distance. Yeast, filamentous and basal unicellular fungi, form distinctive groups based on these analyses, with substantial differences to their polarization network. Our study shows that the fungal polarization network is highly dynamic, even between closely related species, and that functional conservation appears to be achieved by varying the specific components of the fungal polarization repertoire.}, } @article {pmid29931308, year = {2018}, author = {Chen, C and Wang, H and Liu, Z and Chen, X and Tang, J and Meng, F and Shi, W}, title = {Population genomics provide insights into the evolution and adaptation of the eastern honey bee (Apis cerana).}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29931308}, issn = {1537-1719}, abstract = {The mechanisms by which organisms adapt to variable environments are a fundamental question in evolutionary biology and are important to protect important species in response to a changing climate. An interesting candidate to study this question is the honey bee Apis cerana, a keystone pollinator with a wide distribution throughout a large variety of climates, that exhibits rapid dispersal. Here, we re-sequenced the genome of 180 A. cerana individuals from eighteen populations throughout China. Using a population genomics approach, we observed considerable genetic variation in A. cerana. Patterns of genetic differentiation indicate high divergence at the subspecies level, and physical barriers rather than distance are the driving force for population divergence. Estimations of divergence time suggested that the main branches diverged between 300 and 500 ka. Analyses of the population history revealed a substantial influence of the Earth's climate on the effective population size of A. cerana, as increased population sizes were observed during warmer periods. Further analyses identified candidate genes under natural selection that are potentially related to honey bee cognition, temperature adaptation, and olfactory. Based on our results, A. cerana may have great potential in response to climate change. Our study provides fundamental knowledge of the evolution and adaptation of A. cerana.}, } @article {pmid29931306, year = {2018}, author = {Mello, B}, title = {Estimating timetrees with MEGA and the TimeTree resource.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy133}, pmid = {29931306}, issn = {1537-1719}, abstract = {The main outcome of molecular dating, the timetree, provides crucial information for understanding the evolutionary history of lineages and is a requirement of several evolutionary analyses. Although essential, the estimation of divergence times from molecular data is frequently regarded as a complicated task. However, establishing biological timescales can be performed in a straightforward manner, even with large, genome-wide datasets. This protocol presents all the necessary steps to estimate a timetree in the program MEGA X. It also illustrates how the Timetree resource can be a useful tool to obtain chronological information based on previous studies, therefore yielding calibration boundaries.}, } @article {pmid29931290, year = {2018}, author = {Parthasarathy, R and Monette, CE and Bracero, S and S Saha, M}, title = {Methods for field measurement of antibiotic concentrations: limitations and outlook.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy105}, pmid = {29931290}, issn = {1574-6941}, abstract = {The growing prevalence of antibiotic resistance poses an increasingly serious threat to human health. Although an important driver of antibiotic resistance is the continuous exposure of bacteria to sublethal concentrations of antibiotics in natural environments, antibiotic pollutants are not currently tracked globally or systematically. This limits the international capacity to address the rise of antibiotic resistance at its source. To address this lack of data, the development of methods to measure antibiotic concentrations on-site is essential. These methods, ideally, must be sensitive to sublethal concentrations of antibiotics and require minimal technical expertise. Furthermore, factors such as cost, selectivity, biosafety and the ability to multiplex must be evaluated in the context of field use. Based on these criteria, we provide a critical review of current methods in antibiotic detection and evaluate their adaptability for use on-site. We categorize these methods into microbiological assays, physical and chemical assays, immunoassays, aptasensors and whole-cell biosensors. We recommend continued development of a dipstick or microfluidics approach with a bacterial promoter-based mechanism and colorimetric output. This technique would incorporate the advantageous aspects of existing methods, maximize shelf-life and ease-of-use, and require minimal resources to implement in the field.}, } @article {pmid29931252, year = {2018}, author = {Lopez-Fernandez, M and Broman, E and Turner, S and Wu, X and Bertilsson, S and Dopson, M}, title = {Investigation of viable taxa in the deep terrestrial biosphere suggests high rates of nutrient recycling.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, pmid = {29931252}, issn = {1574-6941}, abstract = {The deep biosphere is the largest 'bioreactor' on earth, and microbes inhabiting this biome profoundly influence global nutrient and energy cycles. An important question for deep biosphere microbiology is whether or not specific populations are viable. To address this, we used quantitative PCR and high throughput 16S rRNA gene sequencing of total and viable cells (i.e. with an intact cellular membrane) from three groundwaters with different ages and chemical constituents. There were no statistically significant differences in 16S rRNA gene abundances and microbial diversity between total and viable communities. This suggests that populations were adapted to prevailing oligotrophic conditions and that non-viable cells are rapidly degraded and recycled into new biomass. With higher concentrations of organic carbon, the modern marine and undefined mixed waters hosted a community with a larger range of predicted growth strategies than the ultra-oligotrophic old saline water. These strategies included fermentative and potentially symbiotic lifestyles by candidate phyla that typically have streamlined genomes. In contrast, the old saline waters had more 16S rRNA gene sequences in previously cultured lineages able to oxidize hydrogen and fix carbon dioxide. This matches the paradigm of a hydrogen and carbon dioxide-fed chemolithoautotrophic deep biosphere.}, } @article {pmid29931241, year = {2018}, author = {Botero-Castro, F and Tilak, MK and Justy, F and Catzeflis, F and Delsuc, F and Douzery, EJP}, title = {In Cold Blood: Compositional Bias and Positive Selection Drive the High Evolutionary Rate of Vampire Bats Mitochondrial Genomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {9}, pages = {2218-2239}, pmid = {29931241}, issn = {1759-6653}, abstract = {Mitochondrial genomes of animals have long been considered to evolve under the action of purifying selection. Nevertheless, there is increasing evidence that they can also undergo episodes of positive selection in response to shifts in physiological or environmental demands. Vampire bats experienced such a shift, as they are the only mammals feeding exclusively on blood and possessing anatomical adaptations to deal with the associated physiological requirements (e.g., ingestion of high amounts of liquid water and iron). We sequenced eight new chiropteran mitogenomes including two species of vampire bats, five representatives of other lineages of phyllostomids and one close outgroup. Conducting detailed comparative mitogenomic analyses, we found evidence for accelerated evolutionary rates at the nucleotide and amino acid levels in vampires. Moreover, the mitogenomes of vampire bats are characterized by an increased cytosine (C) content mirrored by a decrease in thymine (T) compared with other chiropterans. Proteins encoded by the vampire bat mitogenomes also exhibit a significant increase in threonine (Thr) and slight reductions in frequency of the hydrophobic residues isoleucine (Ile), valine (Val), methionine (Met), and phenylalanine (Phe). We show that these peculiar substitution patterns can be explained by the co-occurrence of both neutral (mutational bias) and adaptive (positive selection) processes. We propose that vampire bat mitogenomes may have been impacted by selection on mitochondrial proteins to accommodate the metabolism and nutritional qualities of blood meals.}, } @article {pmid29931199, year = {2018}, author = {Kamp, A and Petro, C and Røy, H and Nielsen, S and Carvalho, P and Stief, P and Schramm, A}, title = {Intracellular nitrate in sediments of an oxygen-deficient marine basin is linked to pelagic diatoms.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy122}, pmid = {29931199}, issn = {1574-6941}, abstract = {Intracellular nitrate is an important electron acceptor in oxygen-deficient aquatic environments, either for the nitrate-storing microbes themselves, or for ambient microbial communities through nitrate leakage. This study links the spatial distribution of intracellular nitrate with the abundance and identity of nitrate-storing microbes in sediments of the Bornholm Basin, an environmental showcase for severe hypoxia. Intracellular nitrate (up to 270 nmol cm-3 sediment) was detected at all 18 stations along a 35-km transect through the basin and typically extended as deep as 1.6 cm into the sediment. Intracellular nitrate contents were particularly high at stations where chlorophyll contents suggested high settling rates of pelagic primary production. The depth distribution of intracellular nitrate matched that of the diatom-specific photopigment fucoxanthin in the upper 1.6 cm and calculations support that diatoms are the major nitrate-storing microbes in these sediments. In contrast, other known nitrate-storing microbes, such as sulfide-oxidizing bacteria and foraminifers, played only a minor role, if any. Strikingly, 18S rRNA gene sequencing revealed that the majority of the diatoms in the sediment were pelagic species. We conclude that intracellular nitrate stored by pelagic diatoms is transported to the seafloor by settling phytoplankton blooms, implying a so far overlooked 'biological nitrate pump'.}, } @article {pmid29931163, year = {2018}, author = {Reguera, G}, title = {Microbial nanowires and electroactive biofilms.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy086}, pmid = {29931163}, issn = {1574-6941}, abstract = {Geobacter bacteria are the only microorganisms known to produce conductive appendages or pili to electronically connect cells to extracellular electron acceptors such as iron oxide minerals and uranium. The conductive pili also promote cell-cell aggregation and the formation of electroactive biofilms. The hallmark of these electroactive biofilms is electronic heterogeneity, mediated by coordinated interactions between the conductive pili and matrix-associated cytochromes. Collectively, the matrix-associated electron carriers discharge respiratory electrons from cells in multilayered biofilms to electron-accepting surfaces such as iron oxide coatings and electrodes poised at a metabolically oxidizable potential. The presence of pilus nanowires in the electroactive biofilms also promotes the immobilization and reduction of soluble metals, even when present at toxic concentrations. This review summarizes current knowledge about the composition of the electroactive biofilm matrix and the mechanisms that allow the wired Geobacter biofilms to generate electrical currents and participate in metal redox transformations.}, } @article {pmid29931159, year = {2018}, author = {Leobold, M and Bézier, A and Pichon, A and Herniou, EA and Volkoff, AN and Drezen, JM}, title = {The Domestication of a Large DNA Virus by the Wasp Venturia canescens Involves Targeted Genome Reduction through Pseudogenization.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1745-1764}, pmid = {29931159}, issn = {1759-6653}, mesh = {Animals ; DNA, Viral/genetics ; Evolution, Molecular ; Gene Deletion ; Gene Dosage ; Genes, Viral ; Genome, Insect ; Genome, Viral ; Polydnaviridae/*genetics ; *Pseudogenes ; Virion/genetics ; Wasps/*genetics/*virology ; }, abstract = {Polydnaviruses (PDVs) are compelling examples of viral domestication, in which wasps express a large set of genes originating from a chromosomally integrated virus to produce particles necessary for their reproductive success. Parasitoid wasps generally use PDVs as a virulence gene delivery system allowing the protection of their progeny in the body of parasitized host. However, in the wasp Venturia canescens an independent viral domestication process led to an alternative strategy as the wasp incorporates virulence proteins in viral liposomes named virus-like particles (VLPs), instead of DNA molecules. Proteomic analysis of purified VLPs and transcriptome sequencing revealed the loss of some viral functions. In particular, the genes coding for capsid components are no longer expressed, which explains why VLPs do not incorporate DNA. Here a thorough examination of V. canescens genome revealed the presence of the pseudogenes corresponding to most of the genes involved in lost functions. This strongly suggests that an accumulation of mutations that leads to gene specific pseudogenization precedes the loss of viral genes observed during virus domestication. No evidence was found for block loss of collinear genes, although extensive gene order reshuffling of the viral genome was identified from comparisons between endogenous and exogenous viruses. These results provide the first insights on the early stages of large DNA virus domestication implicating massive genome reduction through gene-specific pseudogenization, a process which differs from the large deletions described for bacterial endosymbionts.}, } @article {pmid29931127, year = {2018}, author = {Catalán, A and Macias-Muñoz, A and Briscoe, AD}, title = {Evolution of sex-biased gene expression and dosage compensation in the eye and brain of Heliconius butterflies.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy111}, pmid = {29931127}, issn = {1537-1719}, abstract = {Differences in behavior and life history traits between females and males are the basis of divergent selective pressures between sexes. It has been suggested that a way for the two sexes to deal with different life history requirements is through sex-biased gene expression. In this study, we performed a comparative sex-biased gene expression analysis of the combined eye and brain transcriptome from five Heliconius species, H. charithonia, H. sara, H. erato, H. melpomene and H. doris, representing five of the main clades from the Heliconius phylogeny. We found that the degree of sexual dimorphism in gene expression is not conserved across Heliconius. Most of the sex-biased genes identified in each species are not sex-biased in any other, suggesting that sexual selection might have driven sexually dimorphic gene expression. Only three genes shared sex-biased expression across multiple species: ultraviolet opsin UVRh1 and orthologs of Drosophila Krüppel-homolog 1 and CG9492. We also observed that in some species female-biased genes have higher evolutionary rates, but in others, male-biased genes show the fastest rates when compared with unbiased genes, suggesting that selective forces driving sex-biased gene evolution in Heliconius act in a sex- and species-specific manner. Furthermore, we found dosage compensation in all the Heliconius tested, providing additional evidence for the conservation of dosage compensation across Lepidoptera. Finally, sex-biased genes are significantly enriched on the Z, a pattern that could be a result of sexually antagonistic selection.}, } @article {pmid29931083, year = {2018}, author = {Dias-Alves, T and Mairal, J and Blum, MGB}, title = {Loter: A software package to infer local ancestry for a wide range of species.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29931083}, issn = {1537-1719}, abstract = {Admixture between populations provides opportunity to study biological adaptation and phenotypic variation. Admixture studies rely on local ancestry inference for admixed individuals, which consists of computing at each locus the number of copies that originate from ancestral source populations. Existing software packages for local ancestry inference are tuned to provide accurate results on human data and recent admixture events. Here, we introduce Loter, an open-source software package that does not require any biological parameter besides haplotype data in order to make local ancestry inference available for a wide range of species. Using simulations, we compare the performance of Loter to HAPMIX, LAMP-LD, and RFMix. HAPMIX is the only software severely impacted by imperfect haplotype reconstruction. Loter is the less impacted software by increasing admixture time when considering simulated and admixed human genotypes. For simulations of admixed Populus genotypes, Loter and LAMP-LD are robust to increasing admixture times by contrast to RFMix. When comparing length of reconstructed and true ancestry tracts, Loter and LAMP-LD provide results whose accuracy is again more robust than RFMix to increasing admixture times. We apply Loter to individuals resulting from admixture between Populus trichocarpa and Populus balsamifera and lengths of ancestry tracts indicate that admixture took place around 100 generations ago. We expect that providing a rapid and parameter-free software for local ancestry inference will make more accessible genomic studies about admixture processes.}, } @article {pmid29931069, year = {2018}, author = {Flynn, JM and Lower, SE and Barbash, DA and Clark, AG}, title = {Rates and Patterns of Mutation in Tandem Repetitive DNA in Six Independent Lineages of Chlamydomonas reinhardtii.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1673-1686}, pmid = {29931069}, issn = {1759-6653}, support = {F32 GM126736/GM/NIGMS NIH HHS/United States ; R01 GM119125/GM/NIGMS NIH HHS/United States ; }, mesh = {Base Sequence ; Chlamydomonas reinhardtii/*genetics ; DNA, Plant/*genetics ; Genome, Chloroplast ; Genome, Plant ; Haploidy ; *Mutation ; Mutation Accumulation ; *Mutation Rate ; *Tandem Repeat Sequences ; }, abstract = {The mutational patterns of large tandem arrays of short sequence repeats remain largely unknown, despite observations of their high levels of variation in sequence and genomic abundance within and between species. Many factors can influence the dynamics of tandem repeat evolution; however, their evolution has only been examined over a limited phylogenetic sample of taxa. Here, we use publicly available whole-genome sequencing data of 85 haploid mutation accumulation lines derived from six geographically diverse Chlamydomonas reinhardtii isolates to investigate genome-wide mutation rates and patterns in tandem repeats in this species. We find that tandem repeat composition differs among ancestral strains, both in genome-wide abundance and presence/absence of individual repeats. Estimated mutation rates (repeat copy number expansion and contraction) were high, averaging 4.3×10-4 per generation per single unit copy. Although orders of magnitude higher than other types of mutation previously reported in C. reinhardtii, these tandem repeat mutation rates were one order of magnitude lower than what has recently been found in Daphnia pulex, even after correcting for lower overall genome-wide satellite abundance in C. reinhardtii. Most high-abundance repeats were related to others by a single mutational step. Correlations of repeat copy number changes within genomes revealed clusters of closely related repeats that were strongly correlated positively or negatively, and similar patterns of correlation arose independently in two different mutation accumulation experiments. Together, these results paint a dynamic picture of tandem repeat evolution in this unicellular alga.}, } @article {pmid29931060, year = {2018}, author = {Takezaki, N}, title = {Global Rate Variation in Bony Vertebrates.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1803-1815}, pmid = {29931060}, issn = {1759-6653}, mesh = {Animals ; Bayes Theorem ; *Evolution, Molecular ; Fossils ; Models, Genetic ; Phylogeny ; Vertebrates/*genetics ; }, abstract = {This study investigated long-term substitution rate differences using three calibration points, divergences between lobe-finned vertebrates and ray-finned fish, between mammals and sauropsids, and between holosteans (gar and bowfin) and teleost fish with amino acid sequence data of 625 genes for 25 bony vertebrates. The result showed that the substitution rate was two to three times higher in the stem branches of lobe-finned vertebrates before the mammal-sauropsid divergence than in amniotes. The rate in the stem branch of ray-finned fish before the holostean-teleost fish divergence was also a few times higher than the holostean rate, whereas it was similar to or somewhat slower than the teleost fish rate. The phylogenetic relationship of coelacanth and lungfish with tetrapod was difficult to determine because of the short interval of the divergences. Considering the high rate in the stem branches, the divergences of coelacanth and lungfish from the stem branch were estimated as 408-427 Ma and 399-414 Ma, respectively, with the interval of 9-13 Myr. With the external calibration of the mammal-sauropsid split, the estimated times for ordinal divergences within eutherian mammals tend to be smaller than those in previous studies that used the calibration points within the lineage, with deeper divergences before the Cretaceous-Paleogene boundary and shallower ones after the boundary. In contrast the estimated times within birds were larger than those of previous studies, with the divergence between Galliformes and Anseriformes ∼80 Ma and that between Galloanserae and Neoaves 110 Ma.}, } @article {pmid29930390, year = {2018}, author = {Leitch, HG and Hajkova, P}, title = {Publisher Correction: Eggs sense high-fat diet.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1196}, doi = {10.1038/s41588-018-0137-5}, pmid = {29930390}, issn = {1546-1718}, abstract = {In the version of this article originally published, a box was misplaced in Fig. 1. The error has been corrected in the HTML and PDF versions of the article.}, } @article {pmid29930357, year = {2018}, author = {Shaver, EC and Burkepile, DE and Silliman, BR}, title = {Publisher Correction: Local management actions can increase coral resilience to thermally-induced bleaching.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1189}, doi = {10.1038/s41559-018-0609-0}, pmid = {29930357}, issn = {2397-334X}, abstract = {In the version of this Brief Communication originally published, the two instances of 'natural-to-high' in the sixth and seventh paragraphs were incorrect; they should have read 'naturally high'.}, } @article {pmid29930353, year = {2018}, author = {Kang, Y and Kuybeda, O and de Waal, PW and Mukherjee, S and Van Eps, N and Dutka, P and Zhou, XE and Bartesaghi, A and Erramilli, S and Morizumi, T and Gu, X and Yin, Y and Liu, P and Jiang, Y and Meng, X and Zhao, G and Melcher, K and Ernst, OP and Kossiakoff, AA and Subramaniam, S and Xu, HE}, title = {Publisher Correction: Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.}, journal = {Nature}, volume = {561}, number = {7724}, pages = {E44}, doi = {10.1038/s41586-018-0302-0}, pmid = {29930353}, issn = {1476-4687}, abstract = {In the PDF version of this Article, owing to a typesetting error, an incorrect figure was used for Extended Data Fig. 5; the correct figure was used in the HTML version. This has been corrected online.}, } @article {pmid29930352, year = {2018}, author = {Atabaki, AH and Moazeni, S and Pavanello, F and Gevorgyan, H and Notaros, J and Alloatti, L and Wade, MT and Sun, C and Kruger, SA and Meng, H and Qubaisi, KA and Wang, I and Zhang, B and Khilo, A and Baiocco, CV and Popović, MA and Stojanović, VM and Ram, RJ}, title = {Publisher Correction: Integrating photonics with silicon nanoelectronics for the next generation of systems on a chip.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {E4}, doi = {10.1038/s41586-018-0247-3}, pmid = {29930352}, issn = {1476-4687}, abstract = {In this Letter, owing to an error during the production process, the author affiliations were listed incorrectly. Affiliation number 5 (Colleges of Nanoscale Science and Engineering, State University of New York (SUNY)) was repeated, and affiliation numbers 6-8 were incorrect. In addition, the phrase "two oxide thickness variants" should have been "two gate oxide thickness variants". These errors have all been corrected online.}, } @article {pmid29930351, year = {2018}, author = {Miller, TB and Chapman, SC and Aravena, M and Ashby, MLN and Hayward, CC and Vieira, JD and Weiß, A and Babul, A and Béthermin, M and Bradford, CM and Brodwin, M and Carlstrom, JE and Chen, CC and Cunningham, DJM and De Breuck, C and Gonzalez, AH and Greve, TR and Harnett, J and Hezaveh, Y and Lacaille, K and Litke, KC and Ma, J and Malkan, M and Marrone, DP and Morningstar, W and Murphy, EJ and Narayanan, D and Pass, E and Perry, R and Phadke, KA and Rennehan, D and Rotermund, KM and Simpson, J and Spilker, JS and Sreevani, J and Stark, AA and Strandet, ML and Strom, AL}, title = {Author Correction: A massive core for a cluster of galaxies at a redshift of 4.3.}, journal = {Nature}, volume = {561}, number = {7721}, pages = {E2}, doi = {10.1038/s41586-018-0285-x}, pmid = {29930351}, issn = {1476-4687}, abstract = {Change history: In this Letter, the Acknowledgements section should have included the following sentence: "The National Radio Astronomy Observatory is a facility of the National Science Foundation operated under cooperative agreement by Associated Universities, Inc.". This omission has been corrected online.}, } @article {pmid29930288, year = {2018}, author = {Iraola, G and Kumar, N}, title = {Surveying what's flushed away.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0047-7}, pmid = {29930288}, issn = {1740-1534}, } @article {pmid29930139, year = {2018}, author = {Smith, ML}, title = {Dinner without reservations.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1370}, doi = {10.1126/science.360.6395.1370}, pmid = {29930139}, issn = {1095-9203}, } @article {pmid29930138, year = {2018}, author = {Jones, MR and Mills, LS and Alves, PC and Callahan, CM and Alves, JM and Lafferty, DJR and Jiggins, FM and Jensen, JD and Melo-Ferreira, J and Good, JM}, title = {Adaptive introgression underlies polymorphic seasonal camouflage in snowshoe hares.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1355-1358}, doi = {10.1126/science.aar5273}, pmid = {29930138}, issn = {1095-9203}, mesh = {Agouti Signaling Protein/genetics ; Animals ; Biological Mimicry/genetics/*physiology ; Gene Expression Regulation ; Genetic Variation ; Hares/genetics/*physiology ; Molting/genetics/physiology ; Seasons ; Skin Pigmentation/genetics/*physiology ; }, abstract = {Snowshoe hares (Lepus americanus) maintain seasonal camouflage by molting to a white winter coat, but some hares remain brown during the winter in regions with low snow cover. We show that cis-regulatory variation controlling seasonal expression of the Agouti gene underlies this adaptive winter camouflage polymorphism. Genetic variation at Agouti clustered by winter coat color across multiple hare and jackrabbit species, revealing a history of recurrent interspecific gene flow. Brown winter coats in snowshoe hares likely originated from an introgressed black-tailed jackrabbit allele that has swept to high frequency in mild winter environments. These discoveries show that introgression of genetic variants that underlie key ecological traits can seed past and ongoing adaptation to rapidly changing environments.}, } @article {pmid29930137, year = {2018}, author = {El-Boustani, S and Ip, JPK and Breton-Provencher, V and Knott, GW and Okuno, H and Bito, H and Sur, M}, title = {Locally coordinated synaptic plasticity of visual cortex neurons in vivo.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1349-1354}, doi = {10.1126/science.aao0862}, pmid = {29930137}, issn = {1095-9203}, support = {R01 EY007023/EY/NEI NIH HHS/United States ; U01 NS090473/NS/NINDS NIH HHS/United States ; F32 EY007023/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Calcium-Calmodulin-Dependent Protein Kinase Type 2/genetics ; Cytoskeletal Proteins/genetics ; Dendritic Spines/physiology ; Electroporation ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Long-Term Potentiation/physiology ; Long-Term Synaptic Depression/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nerve Tissue Proteins/genetics ; Neuronal Plasticity/*physiology ; Neurons/metabolism/*physiology ; Receptors, AMPA/genetics/metabolism ; Synaptic Transmission ; Visual Cortex/cytology/metabolism/*physiology ; }, abstract = {Plasticity of cortical responses in vivo involves activity-dependent changes at synapses, but the manner in which different forms of synaptic plasticity act together to create functional changes in neurons remains unknown. We found that spike timing-induced receptive field plasticity of visual cortex neurons in mice is anchored by increases in the synaptic strength of identified spines. This is accompanied by a decrease in the strength of adjacent spines on a slower time scale. The locally coordinated potentiation and depression of spines involves prominent AMPA receptor redistribution via targeted expression of the immediate early gene product Arc. Hebbian strengthening of activated synapses and heterosynaptic weakening of adjacent synapses thus cooperatively orchestrate cell-wide plasticity of functional neuronal responses.}, } @article {pmid29930136, year = {2018}, author = {Turvey, ST and Bruun, K and Ortiz, A and Hansford, J and Hu, S and Ding, Y and Zhang, T and Chatterjee, HJ}, title = {New genus of extinct Holocene gibbon associated with humans in Imperial China.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1346-1349}, doi = {10.1126/science.aao4903}, pmid = {29930136}, issn = {1095-9203}, mesh = {Animals ; Anthropology ; Biodiversity ; *Extinction, Biological ; Fossils ; Humans ; *Hylobates/anatomy & histology/classification ; Mandible/anatomy & histology ; Skull/anatomy & histology ; }, abstract = {Although all extant apes are threatened with extinction, there is no evidence for human-caused extinctions of apes or other primates in postglacial continental ecosystems, despite intensive anthropogenic pressures associated with biodiversity loss for millennia in many regions. Here, we report a new, globally extinct genus and species of gibbon, Junzi imperialis, described from a partial cranium and mandible from a ~2200- to 2300-year-old tomb from Shaanxi, China. Junzi can be differentiated from extant hylobatid genera and the extinct Quaternary gibbon Bunopithecus by using univariate and multivariate analyses of craniodental morphometric data. Primates are poorly represented in the Chinese Quaternary fossil record, but historical accounts suggest that China may have contained an endemic ape radiation that has only recently disappeared.}, } @article {pmid29930135, year = {2018}, author = {Collett, TE and Oldham, LJ and Smith, RJ and Auger, MW and Westfall, KB and Bacon, D and Nichol, RC and Masters, KL and Koyama, K and van den Bosch, R}, title = {A precise extragalactic test of General Relativity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1342-1346}, doi = {10.1126/science.aao2469}, pmid = {29930135}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Einstein's theory of gravity, General Relativity, has been precisely tested on Solar System scales, but the long-range nature of gravity is still poorly constrained. The nearby strong gravitational lens ESO 325-G004 provides a laboratory to probe the weak-field regime of gravity and measure the spatial curvature generated per unit mass, γ. By reconstructing the observed light profile of the lensed arcs and the observed spatially resolved stellar kinematics with a single self-consistent model, we conclude that γ = 0.97 ± 0.09 at 68% confidence. Our result is consistent with the prediction of 1 from General Relativity and provides a strong extragalactic constraint on the weak-field metric of gravity.}, } @article {pmid29930134, year = {2018}, author = {Fumagalli, L and Esfandiar, A and Fabregas, R and Hu, S and Ares, P and Janardanan, A and Yang, Q and Radha, B and Taniguchi, T and Watanabe, K and Gomila, G and Novoselov, KS and Geim, AK}, title = {Anomalously low dielectric constant of confined water.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1339-1342}, doi = {10.1126/science.aat4191}, pmid = {29930134}, issn = {1095-9203}, abstract = {The dielectric constant ε of interfacial water has been predicted to be smaller than that of bulk water (ε ≈ 80) because the rotational freedom of water dipoles is expected to decrease near surfaces, yet experimental evidence is lacking. We report local capacitance measurements for water confined between two atomically flat walls separated by various distances down to 1 nanometer. Our experiments reveal the presence of an interfacial layer with vanishingly small polarization such that its out-of-plane ε is only ~2. The electrically dead layer is found to be two to three molecules thick. These results provide much-needed feedback for theories describing water-mediated surface interactions and the behavior of interfacial water, and show a way to investigate the dielectric properties of other fluids and solids under extreme confinement.}, } @article {pmid29930133, year = {2018}, author = {Barletta, VR and Bevis, M and Smith, BE and Wilson, T and Brown, A and Bordoni, A and Willis, M and Khan, SA and Rovira-Navarro, M and Dalziel, I and Smalley, R and Kendrick, E and Konfal, S and Caccamise, DJ and Aster, RC and Nyblade, A and Wiens, DA}, title = {Observed rapid bedrock uplift in Amundsen Sea Embayment promotes ice-sheet stability.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1335-1339}, doi = {10.1126/science.aao1447}, pmid = {29930133}, issn = {1095-9203}, abstract = {The marine portion of the West Antarctic Ice Sheet (WAIS) in the Amundsen Sea Embayment (ASE) accounts for one-fourth of the cryospheric contribution to global sea-level rise and is vulnerable to catastrophic collapse. The bedrock response to ice mass loss, glacial isostatic adjustment (GIA), was thought to occur on a time scale of 10,000 years. We used new GPS measurements, which show a rapid (41 millimeters per year) uplift of the ASE, to estimate the viscosity of the mantle underneath. We found a much lower viscosity (4 × 1018 pascal-second) than global average, and this shortens the GIA response time scale from tens to hundreds of years. Our finding requires an upward revision of ice mass loss from gravity data of 10% and increases the potential stability of the WAIS against catastrophic collapse.}, } @article {pmid29930132, year = {2018}, author = {Vos, J and Cattaneo, L and Patchkovskii, S and Zimmermann, T and Cirelli, C and Lucchini, M and Kheifets, A and Landsman, AS and Keller, U}, title = {Orientation-dependent stereo Wigner time delay and electron localization in a small molecule.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1326-1330}, doi = {10.1126/science.aao4731}, pmid = {29930132}, issn = {1095-9203}, abstract = {Attosecond metrology of atoms has accessed the time scale of the most fundamental processes in quantum mechanics. Transferring the time-resolved photoelectric effect from atoms to molecules considerably increases experimental and theoretical challenges. Here we show that orientation- and energy-resolved measurements characterize the molecular stereo Wigner time delay. This observable provides direct information on the localization of the excited electron wave packet within the molecular potential. Furthermore, we demonstrate that photoelectrons resulting from the dissociative ionization process of the CO molecule are preferentially emitted from the carbon end for dissociative 2Σ states and from the center and oxygen end for the 2Π states of the molecular ion. Supported by comprehensive theoretical calculations, this work constitutes a complete spatially and temporally resolved reconstruction of the molecular photoelectric effect.}, } @article {pmid29930131, year = {2018}, author = {Augier, E and Barbier, E and Dulman, RS and Licheri, V and Augier, G and Domi, E and Barchiesi, R and Farris, S and Nätt, D and Mayfield, RD and Adermark, L and Heilig, M}, title = {A molecular mechanism for choosing alcohol over an alternative reward.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1321-1326}, doi = {10.1126/science.aao1157}, pmid = {29930131}, issn = {1095-9203}, mesh = {Alcoholism/genetics/*metabolism/physiopathology ; Amygdala/*metabolism/physiopathology ; Animals ; Behavior, Addictive/genetics/*metabolism/physiopathology ; *Choice Behavior ; Down-Regulation ; Ethanol/administration & dosage/*adverse effects ; GABA Plasma Membrane Transport Proteins/genetics/*metabolism ; Gene Knockdown Techniques ; Humans ; Locomotion ; Male ; RNA, Small Interfering/genetics ; Rats ; Rats, Wistar ; *Reward ; Saccharin/administration & dosage ; Transcription, Genetic ; }, abstract = {Alcohol addiction leads to increased choice of alcohol over healthy rewards. We established an exclusive choice procedure in which ~15% of outbred rats chose alcohol over a high-value reward. These animals displayed addiction-like traits, including high motivation to obtain alcohol and pursuit of this drug despite adverse consequences. Expression of the γ-aminobutyric acid (GABA) transporter GAT-3 was selectively decreased within the amygdala of alcohol-choosing rats, whereas a knockdown of this transcript reversed choice preference of rats that originally chose a sweet solution over alcohol. GAT-3 expression was selectively decreased in the central amygdala of alcohol-dependent people compared to those who died of unrelated causes. Impaired GABA clearance within the amygdala contributes to alcohol addiction, appears to translate between species, and may offer targets for new pharmacotherapies for treating this disorder.}, } @article {pmid29930130, year = {2018}, author = {Grande, JM and Zuluaga, S and Marchini, S}, title = {Casualties of human-wildlife conflict.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1309}, doi = {10.1126/science.aau2465}, pmid = {29930130}, issn = {1095-9203}, mesh = {Animals ; *Animals, Wild ; *Conservation of Natural Resources ; Humans ; }, } @article {pmid29930129, year = {2018}, author = {Shah, SK and Kimmelman, J and Lyerly, AD and Lynch, HF and Miller, FG and Palacios, R and Pardo, CA and Zorrilla, C}, title = {Response-Evaluating human trials: FDA's role.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1308-1309}, doi = {10.1126/science.aau0865}, pmid = {29930129}, issn = {1095-9203}, mesh = {*Clinical Trials as Topic ; Humans ; United States ; *United States Food and Drug Administration ; }, } @article {pmid29930128, year = {2018}, author = {Krause, PR and Gruber, MF}, title = {Evaluating human trials: FDA's role.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1308}, doi = {10.1126/science.aau0591}, pmid = {29930128}, issn = {1095-9203}, mesh = {*Clinical Trials as Topic ; Humans ; United States ; *United States Food and Drug Administration ; }, } @article {pmid29930127, year = {2018}, author = {Finer, M and Novoa, S and Weisse, MJ and Petersen, R and Mascaro, J and Souto, T and Stearns, F and Martinez, RG}, title = {Combating deforestation: From satellite to intervention.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1303-1305}, doi = {10.1126/science.aat1203}, pmid = {29930127}, issn = {1095-9203}, mesh = {*Conservation of Natural Resources ; Environmental Monitoring/*instrumentation ; Satellite Imagery/*instrumentation ; Spacecraft ; }, } @article {pmid29930126, year = {2018}, author = {Kalinin, SV}, title = {Feel the dielectric force.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1302}, doi = {10.1126/science.aat9875}, pmid = {29930126}, issn = {1095-9203}, mesh = {*Microscopy, Atomic Force ; Physical Phenomena ; *Static Electricity ; }, } @article {pmid29930125, year = {2018}, author = {Wu, CH and Derevnina, L and Kamoun, S}, title = {Receptor networks underpin plant immunity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1300-1301}, doi = {10.1126/science.aat2623}, pmid = {29930125}, issn = {1095-9203}, mesh = {Crops, Agricultural/immunology ; *Host-Pathogen Interactions ; Plant Diseases/*immunology ; *Plant Immunity ; Plant Proteins/genetics/*physiology ; Receptors, Immunologic/genetics/*physiology ; }, } @article {pmid29930124, year = {2018}, author = {Spanagel, R}, title = {Aberrant choice behavior in alcoholism.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1298-1299}, doi = {10.1126/science.aau0668}, pmid = {29930124}, issn = {1095-9203}, mesh = {*Alcoholism ; *Choice Behavior ; Ethanol ; Humans ; }, } @article {pmid29930123, year = {2018}, author = {Galway-Witham, J and Stringer, C}, title = {How did Homo sapiens evolve?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1296-1298}, doi = {10.1126/science.aat6659}, pmid = {29930123}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Body Size/genetics ; Fossils ; Genetic Research ; Humans ; *Models, Biological ; Neanderthals/genetics ; Phylogeny ; }, } @article {pmid29930122, year = {2018}, author = {Agrawal, AA and Inamine, H}, title = {Mechanisms behind the monarch's decline.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1294-1296}, doi = {10.1126/science.aat5066}, pmid = {29930122}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; *Butterflies ; *Endangered Species ; *Extinction, Biological ; North America ; Population Dynamics ; }, } @article {pmid29930121, year = {2018}, author = {Wade, L}, title = {Feeding the gods.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1288-1292}, doi = {10.1126/science.360.6395.1288}, pmid = {29930121}, issn = {1095-9203}, mesh = {*Ceremonial Behavior ; *Eating ; History, Ancient ; Humans ; Religion/*history ; *Skull ; }, } @article {pmid29930120, year = {2018}, author = {Vogel, G}, title = {Chinese grave reveals vanished gibbon genus.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1287}, doi = {10.1126/science.360.6395.1287}, pmid = {29930120}, issn = {1095-9203}, } @article {pmid29930119, year = {2018}, author = {Wadman, M}, title = {NIH kills alcohol trial, starts hunt for other suspect studies.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1286}, doi = {10.1126/science.360.6395.1286}, pmid = {29930119}, issn = {1095-9203}, } @article {pmid29930118, year = {2018}, author = {Clery, D}, title = {Radio arrays take shape in the global south.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1285}, doi = {10.1126/science.360.6395.1285}, pmid = {29930118}, issn = {1095-9203}, } @article {pmid29930117, year = {2018}, author = {Cohen, J}, title = {Neanderthal brain organoids come to life.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1284}, doi = {10.1126/science.360.6395.1284}, pmid = {29930117}, issn = {1095-9203}, } @article {pmid29930116, year = {2018}, author = {Langin, K}, title = {Rising bedrock may delay ice sheet collapse.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1283}, doi = {10.1126/science.360.6395.1283}, pmid = {29930116}, issn = {1095-9203}, } @article {pmid29930115, year = {2018}, author = {Stone, R}, title = {Reports of inner-ear damage deepen diplomat controversy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1281-1282}, doi = {10.1126/science.360.6395.1281}, pmid = {29930115}, issn = {1095-9203}, } @article {pmid29930114, year = {2018}, author = {Servick, K}, title = {U.S. center will fight infections with viruses.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1280-1281}, doi = {10.1126/science.360.6395.1280}, pmid = {29930114}, issn = {1095-9203}, } @article {pmid29930113, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1276-1278}, doi = {10.1126/science.360.6395.1276}, pmid = {29930113}, issn = {1095-9203}, } @article {pmid29930112, year = {2018}, author = {Sipp, D and Munsie, M and Sugarman, J}, title = {Emerging stem cell ethics.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1275}, doi = {10.1126/science.aau4720}, pmid = {29930112}, issn = {1095-9203}, mesh = {*Bioethical Issues ; Commerce ; Humans ; Stem Cell Research/economics/*ethics ; Taxes ; Translational Medical Research/economics/*ethics ; }, } @article {pmid29930111, year = {2018}, author = {Shlezinger, N and Irmer, H and Dhingra, S and Beattie, SR and Cramer, RA and Braus, GH and Sharon, A and Hohl, TM}, title = {Response to Comment on "Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {}, doi = {10.1126/science.aas9457}, pmid = {29930111}, issn = {1095-9203}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI093808/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*genetics ; Aspergillus fumigatus ; Fungi/*genetics ; Immunologic Surveillance ; Lung ; }, abstract = {Aouacheria et al question the interpretation of contemporary assays to monitor programmed cell death with apoptosis-like features (A-PCD) in Aspergillus fumigatus Although our study focuses on fungal A-PCD for host immune surveillance and infectious outcomes, the experimental approach incorporates multiple independent A-PCD markers and genetic manipulations based on fungal rather than mammalian orthologs to circumvent the limitations associated with any single approach.}, } @article {pmid29930110, year = {2018}, author = {, and Anttila, V and Bulik-Sullivan, B and Finucane, HK and Walters, RK and Bras, J and Duncan, L and Escott-Price, V and Falcone, GJ and Gormley, P and Malik, R and Patsopoulos, NA and Ripke, S and Wei, Z and Yu, D and Lee, PH and Turley, P and Grenier-Boley, B and Chouraki, V and Kamatani, Y and Berr, C and Letenneur, L and Hannequin, D and Amouyel, P and Boland, A and Deleuze, JF and Duron, E and Vardarajan, BN and Reitz, C and Goate, AM and Huentelman, MJ and Kamboh, MI and Larson, EB and Rogaeva, E and St George-Hyslop, P and Hakonarson, H and Kukull, WA and Farrer, LA and Barnes, LL and Beach, TG and Demirci, FY and Head, E and Hulette, CM and Jicha, GA and Kauwe, JSK and Kaye, JA and Leverenz, JB and Levey, AI and Lieberman, AP and Pankratz, VS and Poon, WW and Quinn, JF and Saykin, AJ and Schneider, LS and Smith, AG and Sonnen, JA and Stern, RA and Van Deerlin, VM and Van Eldik, LJ and Harold, D and Russo, G and Rubinsztein, DC and Bayer, A and Tsolaki, M and Proitsi, P and Fox, NC and Hampel, H and Owen, MJ and Mead, S and Passmore, P and Morgan, K and Nöthen, MM and Rossor, M and Lupton, MK and Hoffmann, P and Kornhuber, J and Lawlor, B and McQuillin, A and Al-Chalabi, A and Bis, JC and Ruiz, A and Boada, M and Seshadri, S and Beiser, A and Rice, K and van der Lee, SJ and De Jager, PL and Geschwind, DH and Riemenschneider, M and Riedel-Heller, S and Rotter, JI and Ransmayr, G and Hyman, BT and Cruchaga, C and Alegret, M and Winsvold, B and Palta, P and Farh, KH and Cuenca-Leon, E and Furlotte, N and Kurth, T and Ligthart, L and Terwindt, GM and Freilinger, T and Ran, C and Gordon, SD and Borck, G and Adams, HHH and Lehtimäki, T and Wedenoja, J and Buring, JE and Schürks, M and Hrafnsdottir, M and Hottenga, JJ and Penninx, B and Artto, V and Kaunisto, M and Vepsäläinen, S and Martin, NG and Montgomery, GW and Kurki, MI and Hämäläinen, E and Huang, H and Huang, J and Sandor, C and Webber, C and Muller-Myhsok, B and Schreiber, S and Salomaa, V and Loehrer, E and Göbel, H and Macaya, A and Pozo-Rosich, P and Hansen, T and Werge, T and Kaprio, J and Metspalu, A and Kubisch, C and Ferrari, MD and Belin, AC and van den Maagdenberg, AMJM and Zwart, JA and Boomsma, D and Eriksson, N and Olesen, J and Chasman, DI and Nyholt, DR and Avbersek, A and Baum, L and Berkovic, S and Bradfield, J and Buono, R and Catarino, CB and Cossette, P and De Jonghe, P and Depondt, C and Dlugos, D and Ferraro, TN and French, J and Hjalgrim, H and Jamnadas-Khoda, J and Kälviäinen, R and Kunz, WS and Lerche, H and Leu, C and Lindhout, D and Lo, W and Lowenstein, D and McCormack, M and Møller, RS and Molloy, A and Ng, PW and Oliver, K and Privitera, M and Radtke, R and Ruppert, AK and Sander, T and Schachter, S and Schankin, C and Scheffer, I and Schoch, S and Sisodiya, SM and Smith, P and Sperling, M and Striano, P and Surges, R and Thomas, GN and Visscher, F and Whelan, CD and Zara, F and Heinzen, EL and Marson, A and Becker, F and Stroink, H and Zimprich, F and Gasser, T and Gibbs, R and Heutink, P and Martinez, M and Morris, HR and Sharma, M and Ryten, M and Mok, KY and Pulit, S and Bevan, S and Holliday, E and Attia, J and Battey, T and Boncoraglio, G and Thijs, V and Chen, WM and Mitchell, B and Rothwell, P and Sharma, P and Sudlow, C and Vicente, A and Markus, H and Kourkoulis, C and Pera, J and Raffeld, M and Silliman, S and Boraska Perica, V and Thornton, LM and Huckins, LM and William Rayner, N and Lewis, CM and Gratacos, M and Rybakowski, F and Keski-Rahkonen, A and Raevuori, A and Hudson, JI and Reichborn-Kjennerud, T and Monteleone, P and Karwautz, A and Mannik, K and Baker, JH and O'Toole, JK and Trace, SE and Davis, OSP and Helder, SG and Ehrlich, S and Herpertz-Dahlmann, B and Danner, UN and van Elburg, AA and Clementi, M and Forzan, M and Docampo, E and Lissowska, J and Hauser, J and Tortorella, A and Maj, M and Gonidakis, F and Tziouvas, K and Papezova, H and Yilmaz, Z and Wagner, G and Cohen-Woods, S and Herms, S and Julià, A and Rabionet, R and Dick, DM and Ripatti, S and Andreassen, OA and Espeseth, T and Lundervold, AJ and Steen, VM and Pinto, D and Scherer, SW and Aschauer, H and Schosser, A and Alfredsson, L and Padyukov, L and Halmi, KA and Mitchell, J and Strober, M and Bergen, AW and Kaye, W and Szatkiewicz, JP and Cormand, B and Ramos-Quiroga, JA and Sánchez-Mora, C and Ribasés, M and Casas, M and Hervas, A and Arranz, MJ and Haavik, J and Zayats, T and Johansson, S and Williams, N and Dempfle, A and Rothenberger, A and Kuntsi, J and Oades, RD and Banaschewski, T and Franke, B and Buitelaar, JK and Arias Vasquez, A and Doyle, AE and Reif, A and Lesch, KP and Freitag, C and Rivero, O and Palmason, H and Romanos, M and Langley, K and Rietschel, M and Witt, SH and Dalsgaard, S and Børglum, AD and Waldman, I and Wilmot, B and Molly, N and Bau, CHD and Crosbie, J and Schachar, R and Loo, SK and McGough, JJ and Grevet, EH and Medland, SE and Robinson, E and Weiss, LA and Bacchelli, E and Bailey, A and Bal, V and Battaglia, A and Betancur, C and Bolton, P and Cantor, R and Celestino-Soper, P and Dawson, G and De Rubeis, S and Duque, F and Green, A and Klauck, SM and Leboyer, M and Levitt, P and Maestrini, E and Mane, S and De-Luca, DM and Parr, J and Regan, R and Reichenberg, A and Sandin, S and Vorstman, J and Wassink, T and Wijsman, E and Cook, E and Santangelo, S and Delorme, R and Rogé, B and Magalhaes, T and Arking, D and Schulze, TG and Thompson, RC and Strohmaier, J and Matthews, K and Melle, I and Morris, D and Blackwood, D and McIntosh, A and Bergen, SE and Schalling, M and Jamain, S and Maaser, A and Fischer, SB and Reinbold, CS and Fullerton, JM and Guzman-Parra, J and Mayoral, F and Schofield, PR and Cichon, S and Mühleisen, TW and Degenhardt, F and Schumacher, J and Bauer, M and Mitchell, PB and Gershon, ES and Rice, J and Potash, JB and Zandi, PP and Craddock, N and Ferrier, IN and Alda, M and Rouleau, GA and Turecki, G and Ophoff, R and Pato, C and Anjorin, A and Stahl, E and Leber, M and Czerski, PM and Cruceanu, C and Jones, IR and Posthuma, D and Andlauer, TFM and Forstner, AJ and Streit, F and Baune, BT and Air, T and Sinnamon, G and Wray, NR and MacIntyre, DJ and Porteous, D and Homuth, G and Rivera, M and Grove, J and Middeldorp, CM and Hickie, I and Pergadia, M and Mehta, D and Smit, JH and Jansen, R and de Geus, E and Dunn, E and Li, QS and Nauck, M and Schoevers, RA and Beekman, AT and Knowles, JA and Viktorin, A and Arnold, P and Barr, CL and Bedoya-Berrio, G and Bienvenu, OJ and Brentani, H and Burton, C and Camarena, B and Cappi, C and Cath, D and Cavallini, M and Cusi, D and Darrow, S and Denys, D and Derks, EM and Dietrich, A and Fernandez, T and Figee, M and Freimer, N and Gerber, G and Grados, M and Greenberg, E and Hanna, GL and Hartmann, A and Hirschtritt, ME and Hoekstra, PJ and Huang, A and Huyser, C and Illmann, C and Jenike, M and Kuperman, S and Leventhal, B and Lochner, C and Lyon, GJ and Macciardi, F and Madruga-Garrido, M and Malaty, IA and Maras, A and McGrath, L and Miguel, EC and Mir, P and Nestadt, G and Nicolini, H and Okun, MS and Pakstis, A and Paschou, P and Piacentini, J and Pittenger, C and Plessen, K and Ramensky, V and Ramos, EM and Reus, V and Richter, MA and Riddle, MA and Robertson, MM and Roessner, V and Rosário, M and Samuels, JF and Sandor, P and Stein, DJ and Tsetsos, F and Van Nieuwerburgh, F and Weatherall, S and Wendland, JR and Wolanczyk, T and Worbe, Y and Zai, G and Goes, FS and McLaughlin, N and Nestadt, PS and Grabe, HJ and Depienne, C and Konkashbaev, A and Lanzagorta, N and Valencia-Duarte, A and Bramon, E and Buccola, N and Cahn, W and Cairns, M and Chong, SA and Cohen, D and Crespo-Facorro, B and Crowley, J and Davidson, M and DeLisi, L and Dinan, T and Donohoe, G and Drapeau, E and Duan, J and Haan, L and Hougaard, D and Karachanak-Yankova, S and Khrunin, A and Klovins, J and Kučinskas, V and Lee Chee Keong, J and Limborska, S and Loughland, C and Lönnqvist, J and Maher, B and Mattheisen, M and McDonald, C and Murphy, KC and Nenadic, I and van Os, J and Pantelis, C and Pato, M and Petryshen, T and Quested, D and Roussos, P and Sanders, AR and Schall, U and Schwab, SG and Sim, K and So, HC and Stögmann, E and Subramaniam, M and Toncheva, D and Waddington, J and Walters, J and Weiser, M and Cheng, W and Cloninger, R and Curtis, D and Gejman, PV and Henskens, F and Mattingsdal, M and Oh, SY and Scott, R and Webb, B and Breen, G and Churchhouse, C and Bulik, CM and Daly, M and Dichgans, M and Faraone, SV and Guerreiro, R and Holmans, P and Kendler, KS and Koeleman, B and Mathews, CA and Price, A and Scharf, J and Sklar, P and Williams, J and Wood, NW and Cotsapas, C and Palotie, A and Smoller, JW and Sullivan, P and Rosand, J and Corvin, A and Neale, BM and Schott, JM and Anney, R and Elia, J and Grigoroiu-Serbanescu, M and Edenberg, HJ and Murray, R}, title = {Analysis of shared heritability in common disorders of the brain.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {}, pmid = {29930110}, issn = {1095-9203}, support = {R01 NS017950/NS/NINDS NIH HHS/United States ; R01 AG058501/AG/NIA NIH HHS/United States ; R25 MH077823/MH/NIMH NIH HHS/United States ; U01 AG016976/AG/NIA NIH HHS/United States ; P01 AG003991/AG/NIA NIH HHS/United States ; P50 AG005681/AG/NIA NIH HHS/United States ; R01 MH106490/MH/NIMH NIH HHS/United States ; P50 AG005133/AG/NIA NIH HHS/United States ; T32 MH076694/MH/NIMH NIH HHS/United States ; J-0901//Parkinson's UK/United Kingdom ; R00 MH101367/MH/NIMH NIH HHS/United States ; R01 AG030653/AG/NIA NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; R01 MH092293/MH/NIMH NIH HHS/United States ; R01 AG041718/AG/NIA NIH HHS/United States ; U01 MH094432/MH/NIMH NIH HHS/United States ; Z99 AG999999/NULL/Intramural NIH HHS/United States ; }, mesh = {Brain Diseases/classification/diagnosis/*genetics ; Genetic Variation ; Genome-Wide Association Study ; Humans ; Mental Disorders/classification/diagnosis/*genetics ; Phenotype ; Quantitative Trait, Heritable ; Risk Factors ; }, abstract = {Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,218 patients and 784,643 control participants and assessed their relationship to 17 phenotypes from 1,191,588 individuals. Psychiatric disorders share common variant risk, whereas neurological disorders appear more distinct from one another and from the psychiatric disorders. We also identified significant sharing between disorders and a number of brain phenotypes, including cognitive measures. Further, we conducted simulations to explore how statistical power, diagnostic misclassification, and phenotypic heterogeneity affect genetic correlations. These results highlight the importance of common genetic variation as a risk factor for brain disorders and the value of heritability-based methods in understanding their etiology.}, } @article {pmid29930109, year = {2018}, author = {Aouacheria, A and Cunningham, KW and Hardwick, JM and Palková, Z and Powers, T and Severin, FF and Váchová, L}, title = {Comment on "Sterilizing immunity in the lung relies on targeting fungal apoptosis-like programmed cell death".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {}, doi = {10.1126/science.aar6910}, pmid = {29930109}, issn = {1095-9203}, support = {R01 NS083373/NS/NINDS NIH HHS/United States ; R21 NS096677/NS/NINDS NIH HHS/United States ; R01 GM077875/GM/NIGMS NIH HHS/United States ; R21 AI115016/AI/NIAID NIH HHS/United States ; }, mesh = {Apoptosis/immunology ; Aspergillosis/*immunology ; Aspergillus fumigatus/*immunology ; Cell Death ; Humans ; Lung/immunology ; }, abstract = {Shlezinger et al (Reports, 8 September 2017, p. 1037) report that the common fungus Aspergillus fumigatus, a cause of aspergillosis, undergoes caspase-dependent apoptosis-like cell death triggered by lung neutrophils. However, the technologies they used do not provide reliable evidence that fungal cells die via a protease signaling cascade thwarted by a fungal caspase inhibitor homologous to human survivin.}, } @article {pmid29930108, year = {2018}, author = {Liu, JJ and Sharma, K and Zangrandi, L and Chen, C and Humphrey, SJ and Chiu, YT and Spetea, M and Liu-Chen, LY and Schwarzer, C and Mann, M}, title = {In vivo brain GPCR signaling elucidated by phosphoproteomics.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {}, doi = {10.1126/science.aao4927}, pmid = {29930108}, issn = {1095-9203}, support = {P30 DA013429/DA/NIDA NIH HHS/United States ; R01 DA041359/DA/NIDA NIH HHS/United States ; R01 AT006899/AT/NCCIH NIH HHS/United States ; }, mesh = {3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer/metabolism/pharmacology ; Analgesics, Non-Narcotic/pharmacology ; Animals ; Anticonvulsants/pharmacology ; Arrestins/metabolism ; Behavior, Animal/drug effects ; Brain/drug effects/*metabolism ; Cell Line, Tumor ; Diterpenes, Clerodane/metabolism/pharmacology ; *High-Throughput Screening Assays ; Humans ; Ligands ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Phenethylamines/metabolism/pharmacology ; Phosphoproteins/*metabolism ; Phosphoric Monoester Hydrolases/antagonists & inhibitors ; Proteomics/*methods ; Receptors, Opioid, kappa/agonists/genetics/*metabolism ; *Signal Transduction/radiation effects ; TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; }, abstract = {A systems view of G protein-coupled receptor (GPCR) signaling in its native environment is central to the development of GPCR therapeutics with fewer side effects. Using the kappa opioid receptor (KOR) as a model, we employed high-throughput phosphoproteomics to investigate signaling induced by structurally diverse agonists in five mouse brain regions. Quantification of 50,000 different phosphosites provided a systems view of KOR in vivo signaling, revealing novel mechanisms of drug action. Thus, we discovered enrichment of the mechanistic target of rapamycin (mTOR) pathway by U-50,488H, an agonist causing aversion, which is a typical KOR-mediated side effect. Consequently, mTOR inhibition during KOR activation abolished aversion while preserving beneficial antinociceptive and anticonvulsant effects. Our results establish high-throughput phosphoproteomics as a general strategy to investigate GPCR in vivo signaling, enabling prediction and modulation of behavioral outcomes.}, } @article {pmid29930094, year = {2018}, author = {Cho, WK and Spille, JH and Hecht, M and Lee, C and Li, C and Grube, V and Cisse, II}, title = {Mediator and RNA polymerase II clusters associate in transcription-dependent condensates.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {412-415}, doi = {10.1126/science.aar4199}, pmid = {29930094}, issn = {1095-9203}, support = {DP2 CA195769/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Chromatin/metabolism ; Embryonic Stem Cells/metabolism ; Enhancer Elements, Genetic ; *Gene Expression Regulation ; Luminescent Proteins/analysis/chemistry ; Mediator Complex/analysis/chemistry/*metabolism ; Mice ; Molecular Imaging/methods ; RNA Polymerase II/analysis/chemistry/*metabolism ; Transcription Factors/*metabolism ; *Transcription, Genetic ; }, abstract = {Models of gene control have emerged from genetic and biochemical studies, with limited consideration of the spatial organization and dynamics of key components in living cells. We used live-cell superresolution and light-sheet imaging to study the organization and dynamics of the Mediator coactivator and RNA polymerase II (Pol II) directly. Mediator and Pol II each form small transient and large stable clusters in living embryonic stem cells. Mediator and Pol II are colocalized in the stable clusters, which associate with chromatin, have properties of phase-separated condensates, and are sensitive to transcriptional inhibitors. We suggest that large clusters of Mediator, recruited by transcription factors at large or clustered enhancer elements, interact with large Pol II clusters in transcriptional condensates in vivo.}, } @article {pmid29930093, year = {2018}, author = {Evans, AM and Parent, LR and Flanders, NC and Bisbey, RP and Vitaku, E and Kirschner, MS and Schaller, RD and Chen, LX and Gianneschi, NC and Dichtel, WR}, title = {Seeded growth of single-crystal two-dimensional covalent organic frameworks.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {52-57}, doi = {10.1126/science.aar7883}, pmid = {29930093}, issn = {1095-9203}, abstract = {Polymerization of monomers into periodic two-dimensional networks provides structurally precise, layered macromolecular sheets that exhibit desirable mechanical, optoelectronic, and molecular transport properties. Two-dimensional covalent organic frameworks (2D COFs) offer broad monomer scope but are generally isolated as powders comprising aggregated nanometer-scale crystallites. We found that 2D COF formation could be controlled using a two-step procedure in which monomers are added slowly to preformed nanoparticle seeds. The resulting 2D COFs are isolated as single-crystalline, micrometer-sized particles. Transient absorption spectroscopy of the dispersed COF nanoparticles revealed improvement in signal quality by two to three orders of magnitude relative to polycrystalline powder samples, and suggests exciton diffusion over longer length scales than those obtained through previous approaches. These findings should enable a broad exploration of synthetic 2D polymer structures and properties.}, } @article {pmid29930092, year = {2018}, author = {Alvarez, RA and Zavala-Araiza, D and Lyon, DR and Allen, DT and Barkley, ZR and Brandt, AR and Davis, KJ and Herndon, SC and Jacob, DJ and Karion, A and Kort, EA and Lamb, BK and Lauvaux, T and Maasakkers, JD and Marchese, AJ and Omara, M and Pacala, SW and Peischl, J and Robinson, AL and Shepson, PB and Sweeney, C and Townsend-Small, A and Wofsy, SC and Hamburg, SP}, title = {Assessment of methane emissions from the U.S. oil and gas supply chain.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {186-188}, pmid = {29930092}, issn = {1095-9203}, support = {9999-NIST//Intramural NIST DOC/United States ; }, abstract = {Methane emissions from the U.S. oil and natural gas supply chain were estimated by using ground-based, facility-scale measurements and validated with aircraft observations in areas accounting for ~30% of U.S. gas production. When scaled up nationally, our facility-based estimate of 2015 supply chain emissions is 13 ± 2 teragrams per year, equivalent to 2.3% of gross U.S. gas production. This value is ~60% higher than the U.S. Environmental Protection Agency inventory estimate, likely because existing inventory methods miss emissions released during abnormal operating conditions. Methane emissions of this magnitude, per unit of natural gas consumed, produce radiative forcing over a 20-year time horizon comparable to the CO2 from natural gas combustion. Substantial emission reductions are feasible through rapid detection of the root causes of high emissions and deployment of less failure-prone systems.}, } @article {pmid29930091, year = {2018}, author = {Sabari, BR and Dall'Agnese, A and Boija, A and Klein, IA and Coffey, EL and Shrinivas, K and Abraham, BJ and Hannett, NM and Zamudio, AV and Manteiga, JC and Li, CH and Guo, YE and Day, DS and Schuijers, J and Vasile, E and Malik, S and Hnisz, D and Lee, TI and Cisse, II and Roeder, RG and Sharp, PA and Chakraborty, AK and Young, RA}, title = {Coactivator condensation at super-enhancers links phase separation and gene control.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {}, pmid = {29930091}, issn = {1095-9203}, support = {R01 GM123511/GM/NIGMS NIH HHS/United States ; R01 CA178765/CA/NCI NIH HHS/United States ; T32 GM007287/GM/NIGMS NIH HHS/United States ; P01 CA042063/CA/NCI NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; R01 DK071900/DK/NIDDK NIH HHS/United States ; T32 CA009172/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Nucleus/drug effects/metabolism ; Conserved Sequence ; Embryonic Stem Cells/metabolism ; *Enhancer Elements, Genetic/drug effects ; Fluorescence Recovery After Photobleaching ; *Gene Expression Regulation/drug effects ; Glycols/pharmacology ; HEK293 Cells ; Humans ; Immunoprecipitation ; Intrinsically Disordered Proteins/chemistry/genetics/*metabolism ; Mediator Complex Subunit 1/chemistry/genetics/*metabolism ; Mice ; Molecular Imaging ; NIH 3T3 Cells ; Nuclear Proteins/chemistry/genetics/*metabolism ; Serine/chemistry/genetics ; Trans-Activators/chemistry/genetics/*metabolism ; Transcription Factors/chemistry/genetics/*metabolism ; }, abstract = {Super-enhancers (SEs) are clusters of enhancers that cooperatively assemble a high density of the transcriptional apparatus to drive robust expression of genes with prominent roles in cell identity. Here we demonstrate that the SE-enriched transcriptional coactivators BRD4 and MED1 form nuclear puncta at SEs that exhibit properties of liquid-like condensates and are disrupted by chemicals that perturb condensates. The intrinsically disordered regions (IDRs) of BRD4 and MED1 can form phase-separated droplets, and MED1-IDR droplets can compartmentalize and concentrate the transcription apparatus from nuclear extracts. These results support the idea that coactivators form phase-separated condensates at SEs that compartmentalize and concentrate the transcription apparatus, suggest a role for coactivator IDRs in this process, and offer insights into mechanisms involved in the control of key cell-identity genes.}, } @article {pmid29930090, year = {2018}, author = {Chong, S and Dugast-Darzacq, C and Liu, Z and Dong, P and Dailey, GM and Cattoglio, C and Heckert, A and Banala, S and Lavis, L and Darzacq, X and Tjian, R}, title = {Imaging dynamic and selective low-complexity domain interactions that control gene transcription.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {}, doi = {10.1126/science.aar2555}, pmid = {29930090}, issn = {1095-9203}, support = {U01 EB021236/EB/NIBIB NIH HHS/United States ; U54 DK107980/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Line, Tumor ; DNA-Binding Proteins/*chemistry ; Genes, Synthetic ; Humans ; Operator Regions, Genetic ; Protein Binding ; *Protein Interaction Domains and Motifs ; RNA Polymerase II/chemistry ; Single Molecule Imaging/*methods ; Transcription Factors/*chemistry ; *Transcription, Genetic ; *Transcriptional Activation ; }, abstract = {Many eukaryotic transcription factors (TFs) contain intrinsically disordered low-complexity sequence domains (LCDs), but how these LCDs drive transactivation remains unclear. We used live-cell single-molecule imaging to reveal that TF LCDs form local high-concentration interaction hubs at synthetic and endogenous genomic loci. TF LCD hubs stabilize DNA binding, recruit RNA polymerase II (RNA Pol II), and activate transcription. LCD-LCD interactions within hubs are highly dynamic, display selectivity with binding partners, and are differentially sensitive to disruption by hexanediols. Under physiological conditions, rapid and reversible LCD-LCD interactions occur between TFs and the RNA Pol II machinery without detectable phase separation. Our findings reveal fundamental mechanisms underpinning transcriptional control and suggest a framework for developing single-molecule imaging screens for drugs targeting gene regulatory interactions implicated in disease.}, } @article {pmid29930089, year = {2018}, author = {Wang, X and Allen, WE and Wright, MA and Sylwestrak, EL and Samusik, N and Vesuna, S and Evans, K and Liu, C and Ramakrishnan, C and Liu, J and Nolan, GP and Bava, FA and Deisseroth, K}, title = {Three-dimensional intact-tissue sequencing of single-cell transcriptional states.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {}, doi = {10.1126/science.aat5691}, pmid = {29930089}, issn = {1095-9203}, support = {F32 MH110144/MH/NIMH NIH HHS/United States ; P50 DA042012/DA/NIDA NIH HHS/United States ; R01 MH099647/MH/NIMH NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; K08 MH113039/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Chromosome Mapping ; Frontal Lobe/cytology/metabolism ; *Imaging, Three-Dimensional ; Male ; Mice ; Mice, Inbred C57BL ; Molecular Imaging ; Neurons/*metabolism ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; Somatosensory Cortex/cytology/metabolism ; *Transcription, Genetic ; *Transcriptome ; Visual Cortex/cytology/metabolism ; }, abstract = {Retrieving high-content gene-expression information while retaining three-dimensional (3D) positional anatomy at cellular resolution has been difficult, limiting integrative understanding of structure and function in complex biological tissues. We developed and applied a technology for 3D intact-tissue RNA sequencing, termed STARmap (spatially-resolved transcript amplicon readout mapping), which integrates hydrogel-tissue chemistry, targeted signal amplification, and in situ sequencing. The capabilities of STARmap were tested by mapping 160 to 1020 genes simultaneously in sections of mouse brain at single-cell resolution with high efficiency, accuracy, and reproducibility. Moving to thick tissue blocks, we observed a molecularly defined gradient distribution of excitatory-neuron subtypes across cubic millimeter-scale volumes (>30,000 cells) and a short-range 3D self-clustering in many inhibitory-neuron subtypes that could be identified and described with 3D STARmap.}, } @article {pmid29929965, year = {2018}, author = {Martin-Martinez, FJ}, title = {Designing nanocellulose materials from the molecular scale.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7174-7175}, pmid = {29929965}, issn = {1091-6490}, mesh = {*Cellulose ; *Nanostructures ; }, } @article {pmid29929964, year = {2018}, author = {Chen, L and Lee, HS and Lee, S}, title = {Close-packed block copolymer micelles induced by temperature quenching.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7218-7223}, pmid = {29929964}, issn = {1091-6490}, abstract = {Close-packed structures of uniformly sized spheres are ubiquitous across diverse material systems including elements, micelles, and colloidal assemblies. However, the controlled access to a specific symmetry of self-assembled close-packed spherical particles has not been well established. We investigated the ordering of spherical block copolymer micelles in aqueous solutions that was induced by rapid temperature changes referred to as quenching. As a function of quench depth, the quenched self-assembled block copolymer micelles formed three different close-packed structures: face-centered cubic (fcc), random stacking of hexagonal-close-packed layers (rhcp), and hexagonal-close-packed (hcp). The induced hcp and rhcp structures were stable for at least a few weeks when maintained at their quench temperatures, but heating or cooling these hcp and rhcp structures transformed both structures to fcc crystallites with coarsening of the crystal grains, which suggests that these noncubic close-packed structures are intermediate states. Time-resolved scattering experiments prove that the micellar rhcp structures do not originate from the rapid growth of competing close-packed structures. We speculate that the long-lived metastable hcp and rhcp structures originate from the small size of crystal grains, which introduces a nonnegligible Laplace pressure to the crystal domains. The reported transitions from the less stable hcp to the more stable rhcp and fcc are experimental observations of Ostwald's rule manifesting the transition order of the key close-packed structures in the crystallization of close-packed uniform spheres.}, } @article {pmid29929963, year = {2018}, author = {Aharoni, H and Xia, Y and Zhang, X and Kamien, RD and Yang, S}, title = {Universal inverse design of surfaces with thin nematic elastomer sheets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7206-7211}, pmid = {29929963}, issn = {1091-6490}, abstract = {Programmable shape-shifting materials can take different physical forms to achieve multifunctionality in a dynamic and controllable manner. Although morphing a shape from 2D to 3D via programmed inhomogeneous local deformations has been demonstrated in various ways, the inverse problem-finding how to program a sheet in order for it to take an arbitrary desired 3D shape-is much harder yet critical to realize specific functions. Here, we address this inverse problem in thin liquid crystal elastomer (LCE) sheets, where the shape is preprogrammed by precise and local control of the molecular orientation of the liquid crystal monomers. We show how blueprints for arbitrary surface geometries can be generated using approximate numerical methods and how local extrinsic curvatures can be generated to assist in properly converting these geometries into shapes. Backed by faithfully alignable and rapidly lockable LCE chemistry, we precisely embed our designs in LCE sheets using advanced top-down microfabrication techniques. We thus successfully produce flat sheets that, upon thermal activation, take an arbitrary desired shape, such as a face. The general design principles presented here for creating an arbitrary 3D shape will allow for exploration of unmet needs in flexible electronics, metamaterials, aerospace and medical devices, and more.}, } @article {pmid29929732, year = {2018}, author = {Ma, LS and Pellegrin, C and Kahmann, R}, title = {Repeat-containing effectors of filamentous pathogens and symbionts.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {123-130}, doi = {10.1016/j.mib.2018.01.007}, pmid = {29929732}, issn = {1879-0364}, abstract = {Pathogenic and symbiotic filamentous microbes secrete effectors which suppress host immune responses and promote a successful colonization. Pathogen effectors are engaged in the arms race with their hosts and because of this they are subject to intense evolutionary pressure. Effectors particularly prone to rapid evolution display repeat-containing domains which can easily expand or contract and accumulate point mutations without altering their original function. In this review we address the diversity of function in such repeat-containing effectors, focus on new findings and point out avenues for future work.}, } @article {pmid29929544, year = {2018}, author = {Herath, NC and Kudagammana, T and Sanathchandra, TT and Gamage, HK and Razik, IM and Liynapathirana, V}, title = {Brief report: Parental attitudes and knowledge on routine childhood immunization: an experience from Central Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {402}, pmid = {29929544}, issn = {1756-0500}, mesh = {Adult ; Child ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Immunization ; India ; Male ; *Parents ; Patient Acceptance of Health Care ; Sri Lanka ; *Vaccination ; Young Adult ; }, abstract = {OBJECTIVES: A lack of correct awareness about immunization among parents put them at risk of falling prey to the anti-vaccine movement. This risk is present even in countries with a high vaccine uptake. This study was done with the objective of assessing the awareness of parents childhood vaccination.

RESULTS: In this study conducted among 141 parents accompanying children to a routine clinic we found that 53.2% of the participants had average or above average knowledge. Level of knowledge was associated with the level of education (OR: 2.7, 95% CI 1.4-5.4) and the sex of the parent (OR: 3.4, 95% CI 1.2-9.3). While our sample size is small, we recommend educational programmes for parents to strengthen their knowledge on vaccination to safeguard the continuity of a successful control of vaccine preventable diseases.}, } @article {pmid29929534, year = {2018}, author = {Garg, S and Huifu, H and Kaul, SC and Wadhwa, R}, title = {Integration of conventional cell viability assays for reliable and reproducible read-outs: experimental evidence.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {403}, pmid = {29929534}, issn = {1756-0500}, mesh = {Animals ; *Biological Assay ; Cell Count ; Cell Line ; *Cell Survival ; Signal Transduction ; }, abstract = {OBJECTIVE: Short-term viability assays of cultured cells in 96-well plates are routinely used to determine the cytotoxicity or safety of drugs. These are often based on the formation of chromogen, generated selectively in viable cells. The innate problems of such short-term cell viability assays include (i) effect of drugs is determined by cell density (ii) some drugs have slow/gradual effect and hence may escape such assays, (iii) cell morphology that reveal significant hints to molecular signaling underlining the effect of drugs cannot be effectively captured, (iv) long-term effect on viability and clonogenic potential of cells cannot be determined and (v) herbal extracts often possess intrinsic color that interferes with spectrophotometer estimation. In light of the ease and importance of cell culture-based assessment of drug safety and cytotoxicity, we attempted to combine the conventional cell-based assays in a way that allows multiple readouts (quantitative and qualitative) from a single experiment, and avoids the drawbacks of color interference.

RESULTS: We have established and validated (using 16 types of cultured mammalian cells) a Quantitative and Qualitative Cell Viability assay in 12-well cell culture plates. It overcomes several shortcomings as discussed above and allows long-term observations on cell morphology and clonogenicity.}, } @article {pmid29929531, year = {2018}, author = {Varland, S and Arnesen, T}, title = {Investigating the functionality of a ribosome-binding mutant of NAA15 using Saccharomyces cerevisiae.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {404}, pmid = {29929531}, issn = {1756-0500}, support = {261981//Norges Forskningsråd/ ; 230865//Norges Forskningsråd/ ; 249843//Norges Forskningsråd/ ; 912176//Helse Vest/ ; }, mesh = {Acetylation ; Amino Acid Sequence ; Humans ; N-Terminal Acetyltransferase A/*genetics/metabolism ; N-Terminal Acetyltransferase E/*genetics/metabolism ; Protein Processing, Post-Translational ; Ribosomes ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins ; }, abstract = {OBJECTIVE: N-terminal acetylation is a common protein modification that occurs preferentially co-translationally as the substrate N-terminus is emerging from the ribosome. The major N-terminal acetyltransferase complex A (NatA) is estimated to N-terminally acetylate more than 40% of the human proteome. To form a functional NatA complex the catalytic subunit NAA10 must bind the auxiliary subunit NAA15, which properly folds NAA10 for correct substrate acetylation as well as anchors the entire complex to the ribosome. Mutations in these two genes are associated with various neurodevelopmental disorders in humans. The aim of this study was to investigate the in vivo functionality of a Schizosaccharomyces pombe NAA15 mutant that is known to prevent NatA from associating with ribosomes, but retains NatA-specific activity in vitro.

RESULTS: Here, we show that Schizosaccharomyces pombe NatA can functionally replace Saccharomyces cerevisiae NatA. We further demonstrate that the NatA ribosome-binding mutant Naa15 ΔN K6E is unable to rescue the temperature-sensitive growth phenotype of budding yeast lacking NatA. This finding indicates the in vivo importance of the co-translational nature of NatA-mediated N-terminal acetylation.}, } @article {pmid29929515, year = {2018}, author = {Kowalski, L and Bragoszewski, P and Khmelinskii, A and Glow, E and Knop, M and Chacinska, A}, title = {Determinants of the cytosolic turnover of mitochondrial intermembrane space proteins.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {66}, pmid = {29929515}, issn = {1741-7007}, abstract = {BACKGROUND: The proteome of mitochondria comprises mostly proteins that originate as precursors in the cytosol. Before import into the organelle, such proteins are exposed to cytosolic quality control mechanisms. Multiple lines of evidence indicate a significant contribution of the major cytosolic protein degradation machinery, the ubiquitin-proteasome system, to the quality control of mitochondrial proteins. Proteins that are directed to the mitochondrial intermembrane space (IMS) exemplify an entire class of mitochondrial proteins regulated by proteasomal degradation. However, little is known about how these proteins are selected for degradation.

RESULTS: The present study revealed the heterogeneous cytosolic stability of IMS proteins. Using a screening approach, we found that different cytosolic factors are responsible for the degradation of specific IMS proteins, with no single common factor involved in the degradation of all IMS proteins. We found that the Cox12 protein is rapidly degraded when localized to the cytosol, thus providing a sensitive experimental model. Using Cox12, we found that lysine residues but not conserved cysteine residues are among the degron features important for protein ubiquitination. We observed the redundancy of ubiquitination components, with significant roles of Ubc4 E2 ubiquitin-conjugating enzyme and Rsp5 E3 ubiquitin ligase. The amount of ubiquitinated Cox12 was inversely related to mitochondrial import efficiency. Importantly, we found that precursor protein ubiquitination blocks its import into mitochondria.

CONCLUSIONS: The present study confirms the involvement of ubiquitin-proteasome system in the quality control of mitochondrial IMS proteins in the cytosol. Notably, ubiquitination of IMS proteins prohibits their import into mitochondria. Therefore, ubiquitination directly affects the availability of precursor proteins for organelle biogenesis. Importantly, despite their structural similarities, IMS proteins are not selected for degradation in a uniform way. Instead, specific IMS proteins rely on discrete components of the ubiquitination machinery to mediate their clearance by the proteasome.}, } @article {pmid29929505, year = {2018}, author = {Zöller, E and Todd Alexander, R and Herrmann, JM}, title = {Proteasomal degradation competes with Mia40-mediated import into mitochondria.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {63}, pmid = {29929505}, issn = {1741-7007}, mesh = {Cytosol ; Mitochondria ; *Mitochondrial Membrane Transport Proteins ; Protein Transport ; *Saccharomyces cerevisiae Proteins ; }, abstract = {Tandem fluorescent protein timers are elegant tools to determine proteolytic stabilities of cytosolic proteins with high spatial and temporal resolution. In a new study published in BMC Biology, Kowalski et al. fused timers to precursors of proteins of the mitochondrial intermembrane space and found that they are under surveillance of the ubiquitin-proteasome system. Ubiquitination at lysine residues of these precursors directly inhibits their translocation into the intermembrane space and targets them for proteasomal degradation.}, } @article {pmid29929489, year = {2018}, author = {Claw, KG and George, RD and MacCoss, MJ and Swanson, WJ}, title = {Quantitative evolutionary proteomics of seminal fluid from primates with different mating systems.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {488}, pmid = {29929489}, issn = {1471-2164}, support = {DEG-0718124//National Science Foundation/ ; HD057974//National Institutes of Health/ ; HD042563//National Institutes of Health/ ; HD076862//National Institute of Child Health and Human Development/ ; R01 HD076862/HD/NICHD NIH HHS/United States ; P51 RR000165/RR/NCRR NIH HHS/United States ; R01 HD057974/HD/NICHD NIH HHS/United States ; R01 HD042563/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Chromatography, Liquid ; *Evolution, Molecular ; Genomics ; Male ; Mass Spectrometry ; Phylogeny ; Primates ; Proteomics/*methods ; Reproduction/physiology ; Semen/*metabolism ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Genomic data from various organisms have been used to study how sexual selection has shaped genetic diversity in reproductive proteins, and in particular, to elucidate how mating systems may have influenced evolution at the molecular and phenotypic levels. However, large-scale proteomic data including protein identifications and abundances are only now entering the field of evolutionary and comparative genomics. Variation in both protein sequence and expression level may play important roles in the evolution of sexual traits and behaviors.

RESULTS: Here, we broadly analyze the components of seminal fluid from primates with diverse mating systems ranging from monogamous to polygynous, and include genomics, proteomics, phylogenetic and quantitative characters into our framework. Our analyses show that seminal fluid proteins are undergoing rapid evolution and some of these quickly evolving proteins may be influenced by sexual selection. Through evolutionary analyses and protein abundance differences, we identified 84 genes whose evolutionary rates or expression levels were correlated with mating system and other sexual characters. We found that many proteins differ in abundance between monogamous and polygynous primate mating systems. Many of these proteins are enriched in the copulatory plug pathway, which suggests that post-zygotic selective barriers are important regardless of mating system type.

CONCLUSIONS: This work is the first to comprehensively compare seminal fluid proteins between human and non-human primates using high-throughput proteomics. Our findings highlight the impact of mating system variation on seminal fluid protein evolution and abundance.}, } @article {pmid29929481, year = {2018}, author = {Smid, M and Coebergh van den Braak, RRJ and van de Werken, HJG and van Riet, J and van Galen, A and de Weerd, V and van der Vlugt-Daane, M and Bril, SI and Lalmahomed, ZS and Kloosterman, WP and Wilting, SM and Foekens, JA and IJzermans, JNM and , and Martens, JWM and Sieuwerts, AM}, title = {Gene length corrected trimmed mean of M-values (GeTMM) processing of RNA-seq data performs similarly in intersample analyses while improving intrasample comparisons.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {236}, pmid = {29929481}, issn = {1471-2105}, support = {322737//European Research Council/International ; }, abstract = {BACKGROUND: Current normalization methods for RNA-sequencing data allow either for intersample comparison to identify differentially expressed (DE) genes or for intrasample comparison for the discovery and validation of gene signatures. Most studies on optimization of normalization methods typically use simulated data to validate methodologies. We describe a new method, GeTMM, which allows for both inter- and intrasample analyses with the same normalized data set. We used actual (i.e. not simulated) RNA-seq data from 263 colon cancers (no biological replicates) and used the same read count data to compare GeTMM with the most commonly used normalization methods (i.e. TMM (used by edgeR), RLE (used by DESeq2) and TPM) with respect to distributions, effect of RNA quality, subtype-classification, recurrence score, recall of DE genes and correlation to RT-qPCR data.

RESULTS: We observed a clear benefit for GeTMM and TPM with regard to intrasample comparison while GeTMM performed similar to TMM and RLE normalized data in intersample comparisons. Regarding DE genes, recall was found comparable among the normalization methods, while GeTMM showed the lowest number of false-positive DE genes. Remarkably, we observed limited detrimental effects in samples with low RNA quality.

CONCLUSIONS: We show that GeTMM outperforms established methods with regard to intrasample comparison while performing equivalent with regard to intersample normalization using the same normalized data. These combined properties enhance the general usefulness of RNA-seq but also the comparability to the many array-based gene expression data in the public domain.}, } @article {pmid29929475, year = {2018}, author = {De Paris, R and Vahl Quevedo, C and Ruiz, DD and Gargano, F and de Souza, ON}, title = {A selective method for optimizing ensemble docking-based experiments on an InhA Fully-Flexible receptor model.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {235}, pmid = {29929475}, issn = {1471-2105}, abstract = {BACKGROUND: In the rational drug design process, an ensemble of conformations obtained from a molecular dynamics simulation plays a crucial role in docking experiments. Some studies have found that Fully-Flexible Receptor (FFR) models predict realistic binding energy accurately and improve scoring to enhance selectiveness. At the same time, methods have been proposed to reduce the high computational costs involved in considering the explicit flexibility of proteins in receptor-ligand docking. This study introduces a novel method to optimize ensemble docking-based experiments by reducing the size of an InhA FFR model at docking runtime and scaling docking workflow invocations on cloud virtual machines.

RESULTS: First, in order to find the most affordable cost-benefit pool of virtual machines, we evaluated the performance of the docking workflow invocations in different configurations of Azure instances. Second, we validated the gains obtained by the proposed method based on the quality of the Reduced Fully-Flexible Receptor (RFFR) models produced using AutoDock4.2. The analyses show that the proposed method reduced the model size by approximately 50% while covering at least 86% of the best docking results from the 74 ligands tested. Third, we tested our novel method using AutoDock Vina, a different docking software, and showed the positive accuracy achieved in the resulting RFFR models. Finally, our results demonstrated that the method proposed optimized ensemble docking experiments and is applicable to different docking software. In addition, it detected new binding modes, which would be unreachable if employing only the rigid structure used to generate the InhA FFR model.

CONCLUSIONS: Our results showed that the selective method is a valuable strategy for optimizing ensemble docking-based experiments using different docking software. The RFFR models produced by discarding non-promising snapshots from the original model are accurately shaped for a larger number of ligands, and the elapsed time spent in the ensemble docking experiments are considerably reduced.}, } @article {pmid29929474, year = {2018}, author = {Coenen, H and Viaene, T and Vandenbussche, M and Geuten, K}, title = {TM8 represses developmental timing in Nicotiana benthamiana and has functionally diversified in angiosperms.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {129}, pmid = {29929474}, issn = {1471-2229}, support = {35040//IWT/ ; C24/17/037//KULeuven/ ; OT/12/053//KULeuven/ ; G065713N//FWO/ ; }, mesh = {Biological Evolution ; Conserved Sequence/genetics/physiology ; Genes, Plant/genetics/physiology ; MADS Domain Proteins/*genetics/physiology ; Magnoliopsida/genetics/*growth & development ; Petunia/genetics/physiology ; Phylogeny ; Plant Proteins/*genetics/physiology ; Tobacco/genetics/*growth & development ; Transcriptome ; }, abstract = {BACKGROUND: MADS-box genes are key regulators of plant reproductive development and members of most lineages of this gene family have been extensively studied. However, the function and diversification of the ancient TM8 lineage remains elusive to date. The available data suggest a possible function in flower development in tomato and fast evolution through numerous gene loss events in flowering plants.

RESULTS: We show the broad conservation of TM8 within angiosperms and find that in contrast to other MADS-box gene lineages, no gene duplicates have been retained after major whole genome duplication events. Through knock-down of NbTM8 by virus induced gene silencing in Nicotiana benthamiana, we show that NbTM8 represses miR172 together with another MADS-box gene, SHORT VEGETATIVE PHASE (NbSVP). In the closely related species Petunia hybrida, PhTM8 is not expressed under the conditions we investigated and consistent with this, a knock-out mutant did not show a phenotype. Finally, we generated transgenic tomato plants in which TM8 was silenced or ectopically expressed, but these plants did not display a clear phenotype. Therefore, no clear function could be confirmed for Solanum lycopersium.

CONCLUSIONS: While the presence of TM8 is generally conserved, it remains difficult to propose a general function in angiosperms. Based on all the available data to date, supplemented with our own results, TM8 function seems to have diversified quickly throughout angiosperms and acts as repressor of miR172 in Nicotiana benthamiana, together with NbSVP.}, } @article {pmid29928986, year = {2018}, author = {Braun, R and Bachmann, S and Schönberger, N and Matys, S and Lederer, F and Pollmann, K}, title = {Peptides as biosorbents - Promising tools for resource recovery.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {649-658}, doi = {10.1016/j.resmic.2018.06.001}, pmid = {29928986}, issn = {1769-7123}, mesh = {Adsorption ; Bacteriophages/chemistry/genetics/*metabolism ; Biotechnology/*methods ; Cobalt/chemistry/metabolism ; Nickel/chemistry/metabolism ; Peptides/*chemistry/genetics/metabolism ; Terbium/chemistry/metabolism ; Waste Water/chemistry ; }, abstract = {Despite many innovations, meeting both economic and ecological requirements remains challenging for conventional resource recovery technology. The development of highly selective peptides puts a new competitor on the market. We present an approach to identify peptides for resource recovery using Phage Surface Display. Here, we describe the development of peptides for binding of rare earth element terbium-containing solids and for removal and enrichment of the heavy metal ions of cobalt and nickel out of waste waters and leaching solutions. We identified phage displaying specific peptides with ∼100× enhanced affinity towards terbium-containing solids or ∼20× enhanced affinity towards nickel (∼3× cobalt).}, } @article {pmid29928868, year = {2018}, author = {Lin, JM and Taroc, EZM and Frias, JA and Prasad, A and Catizone, AN and Sammons, MA and Forni, PE}, title = {The transcription factor Tfap2e/AP-2ε plays a pivotal role in maintaining the identity of basal vomeronasal sensory neurons.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {67-82}, doi = {10.1016/j.ydbio.2018.06.007}, pmid = {29928868}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation/physiology ; GABAergic Neurons/*metabolism ; Gene Expression Regulation, Developmental/*physiology ; Mice ; Mice, Transgenic ; Mutation ; Nasal Mucosa/cytology/*embryology ; Sensory Receptor Cells/cytology/*metabolism ; Transcription Factor AP-2/*biosynthesis/genetics ; Vomeronasal Organ/cytology/*embryology ; }, abstract = {The identity of individual neuronal cell types is defined and maintained by the expression of specific combinations of transcriptional regulators that control cell type-specific genetic programs. The epithelium of the vomeronasal organ of mice contains two major types of vomeronasal sensory neurons (VSNs): 1) the apical VSNs which express vomeronasal 1 receptors (V1r) and the G-protein subunit Gαi2 and; 2) the basal VSNs which express vomeronasal 2 receptors (V2r) and the G-protein subunit Gαo. Both cell types originate from a common pool of progenitors and eventually acquire apical or basal identity through largely unknown mechanisms. The transcription factor AP-2ε, encoded by the Tfap2e gene, plays a role in controlling the development of GABAergic interneurons in the main and accessory olfactory bulb (AOB), moreover AP-2ε has been previously described to be expressed in the basal VSNs. Here we show that AP-2ε is expressed in post-mitotic VSNs after they commit to the basal differentiation program. Loss of AP-2ε function resulted in reduced number of basal VSNs and in an increased number of neurons expressing markers of the apical lineage. Our work suggests that AP-2ε, which is expressed in late phases of differentiation, is not needed to initiate the apical-basal differentiation dichotomy but for maintaining the basal VSNs' identity. In AP-2ε mutants we observed a large number of cells that entered the basal program can express apical genes, our data suggest that differentiated VSNs of mice retain a notable level of plasticity.}, } @article {pmid29928306, year = {2018}, author = {Castellani, M and Heino, M and Gilbey, J and Araki, H and Svåsand, T and Glover, KA}, title = {Modeling fitness changes in wild Atlantic salmon populations faced by spawning intrusion of domesticated escapees.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {1010-1025}, pmid = {29928306}, issn = {1752-4571}, abstract = {Genetic interaction between domesticated escapees and wild conspecifics represents a persistent challenge to an environmentally sustainable Atlantic salmon aquaculture industry. We used a recently developed eco-genetic model (IBSEM) to investigate potential changes in a wild salmon population subject to spawning intrusion from domesticated escapees. At low intrusion levels (5%-10% escapees), phenotypic and demographic characteristics of the recipient wild population only displayed weak changes over 50 years and only at high intrusion levels (30%-50% escapees) were clear changes visible in this period. Our modeling also revealed that genetic changes in phenotypic and demographic characteristics were greater in situations where strayers originating from a neighboring wild population were domestication-admixed and changed in parallel with the focal wild population, as opposed to nonadmixed. While recovery in the phenotypic and demographic characteristics was observed in many instances after domesticated salmon intrusion was halted, in the most extreme intrusion scenario, the population went extinct. Based upon results from these simulations, together with existing knowledge, we suggest that a combination of reduced spawning success of domesticated escapees, natural selection purging maladapted phenotypes/genotypes from the wild population, and phenotypic plasticity, buffer the rate and magnitude of change in phenotypic and demographic characteristics of wild populations subject to spawning intrusion of domesticated escapees. The results of our simulations also suggest that under specific conditions, natural straying among wild populations may buffer genetic changes in phenotypic and demographic characteristics resulting from introgression of domesticated escapees and that variation in straying in time and space may contribute to observed differences in domestication-driven introgression among native populations.}, } @article {pmid29928305, year = {2018}, author = {Hovick, SM and McArdle, A and Harrison, SK and Regnier, EE}, title = {A mosaic of phenotypic variation in giant ragweed (Ambrosia trifida): Local- and continental-scale patterns in a range-expanding agricultural weed.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {995-1009}, pmid = {29928305}, issn = {1752-4571}, abstract = {Spatial patterns of trait variation across a species' range have implications for population success and evolutionary change potential, particularly in range-expanding and weedy species that encounter distinct selective pressures at large and small spatial scales simultaneously. We investigated intraspecific trait variation in a common garden experiment with giant ragweed (Ambrosia trifida), a highly variable agricultural weed with an expanding geographic range and broad ecological amplitude. Our study included paired populations from agricultural and natural riparian habitats in each of seven regions ranging east to west from the core of the species' distribution in central Ohio to southeastern Minnesota, which is nearer the current invasion front. We observed trait variation across both large- and small-scale putative selective gradients. At large scales, giant ragweed populations from the westernmost locations were nearly four times more fecund and had a nearly 50% increase in reproductive allocation compared to populations from the core. The degree of surface texture on fruits also declined from east to west. Greater fecundity in the west represents a putative trade-off between fruit size and fruit number across the study region, although no such trade-off was found across individual plants. This pattern may effectively result in greater propagule pressure closer to the invasion front. At smaller spatial scales, plants from agricultural populations emerged later and were smaller than plants from riparian populations. However, because plants from agricultural populations allocated more biomass to reproduction, total fecundity did not differ across habitats. Our emergence data are consistent with previous observations showing delayed emergence in agricultural compared to natural populations; thus evolutionary change may be predictable as giant ragweed continues spreading into agricultural fields throughout North America. These shifts in life-history strategy apparently bear no fecundity cost, suggesting that giant ragweed's success can be attributed at least in part to its substantial adaptive potential.}, } @article {pmid29928304, year = {2018}, author = {Young, EF and Tysklind, N and Meredith, MP and de Bruyn, M and Belchier, M and Murphy, EJ and Carvalho, GR}, title = {Stepping stones to isolation: Impacts of a changing climate on the connectivity of fragmented fish populations.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {978-994}, pmid = {29928304}, issn = {1752-4571}, abstract = {In the marine environment, understanding the biophysical mechanisms that drive variability in larval dispersal and population connectivity is essential for estimating the potential impacts of climate change on the resilience and genetic structure of populations. Species whose populations are small, isolated and discontinuous in distribution will differ fundamentally in their response and resilience to environmental stress, compared with species that are broadly distributed, abundant and frequently exchange conspecifics. Here, we use an individual-based modelling approach, combined with a population genetics projection model, to consider the impacts of a warming climate on the population connectivity of two contrasting Antarctic fish species, Notothenia rossii and Champsocephalus gunnari. Focussing on the Scotia Sea region, sea surface temperatures are predicted to increase significantly by the end of the 21st century, resulting in reduced planktonic duration and increased egg and larval mortality. With shorter planktonic durations, the results of our study predict reduced dispersal of both species across the Scotia Sea, from Antarctic Peninsula sites to islands in the north and east, and increased dispersal among neighbouring sites, such as around the Antarctic Peninsula. Increased mortality modified the magnitude of population connectivity but had little effect on the overall patterns. Whilst the predicted changes in connectivity had little impact on the projected regional population genetic structure of N. rossii, which remained broadly genetically homogeneous within distances of ~1,500 km, the genetic isolation of C. gunnari populations in the northern Scotia Sea was predicted to increase with rising sea temperatures. Our study highlights the potential for increased isolation of island populations in a warming world, with implications for the resilience of populations and their ability to adapt to ongoing environmental change, a matter of high relevance to fisheries and ecosystem-level management.}, } @article {pmid29928303, year = {2018}, author = {Sørdalen, TK and Halvorsen, KT and Harrison, HB and Ellis, CD and Vøllestad, LA and Knutsen, H and Moland, E and Olsen, EM}, title = {Harvesting changes mating behaviour in European lobster.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {963-977}, pmid = {29928303}, issn = {1752-4571}, abstract = {Removing individuals from a wild population can affect the availability of prospective mates and the outcome of competitive interactions, with subsequent effects on mating patterns and sexual selection. Consequently, the rate of harvest-induced evolution is predicted to be strongly dependent on the strength and dynamics of sexual selection, yet there is limited empirical knowledge on the interplay between selective harvesting and the mating systems of exploited species. In this study, we used genetic parentage assignment to compare mating patterns of the highly valued and overexploited European lobster (Homarus gammarus) in a designated lobster reserve and nearby fished area in southern Norway. In the area open to fishing, the fishery is regulated by a closed season, a minimum legal size and a ban on the harvest of egg-bearing females. Due to the differences in size and sex-specific fishing mortality between the two areas, males and females are of approximately equal average size in the fished area, whereas males tend to be larger in the reserve. Our results show that females would mate with males larger than their own body size, but the relative size difference was significantly larger in the reserve. Sexual selection acted positively on both body size and claw size in males in the reserve, while it was nonsignificant in fished areas. This strongly suggests that size truncation of males by fishing reduces the variability of traits that sexual selection acts upon. If fisheries continue to target large individuals (particularly males) with higher relative reproductive success, the weakening of sexual selection will likely accelerate fisheries-induced evolution towards smaller body size.}, } @article {pmid29928302, year = {2018}, author = {Bigelow, PJ and Loescher, W and Hancock, JF and Grumet, R}, title = {Influence of intergenotypic competition on multigenerational persistence of abiotic stress resistance transgenes in populations of Arabidopsis thaliana.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {950-962}, pmid = {29928302}, issn = {1752-4571}, abstract = {Reducing crop losses due to abiotic stresses is a major target of agricultural biotechnology that will increase with climate change and global population growth. Concerns, however, have been raised about potential ecological impacts if transgenes become established in wild populations and cause increased competitiveness of weedy or invasive species. Potential risks will be a function of transgene movement, population sizes, and fitness effects on the recipient population. While key components influencing gene flow have been extensively investigated, there have been few studies on factors subsequent to transgene movement that can influence persistence and competitiveness. Here, we performed multiyear, multigenerational, assessment to examine fitness effects and persistence of three mechanistically different abiotic stress tolerance genes: C-repeat binding factor 3/drought responsive element binding factor 1a (CBF3/DREB1a); Salt overly sensitive 1 (SOS1); and Mannose-6-phosphate reductase (M6PR). Transgenic Arabidopsis thaliana overexpressing these genes were grown in pure populations and in competition with wild-type (WT) parents for six generations spanning a range of field environment conditions. Growth, development, biomass, seed production, and transgene frequency were measured at each generation. Seed planted for each generation was obtained from the previous generation as would occur during establishment of a new genotype in the environment. The three transgenes exhibited different fitness effects and followed different establishment trajectories. In comparison with pure populations, CBF3 lines exhibited reduced dry weight, seed yield, and viable seed yield, relative to WT background. In contrast, overexpression of SOS1 and M6PR did not significantly impact productivity measures in pure populations. In competition with WT, negative fitness effects were magnified. Transgene frequencies were significantly reduced for CBF3 and SOS1 while frequencies of M6PR appeared to be subject to genetic drift. These studies demonstrate the importance of fitness effects and intergenotype competition in influencing persistence of transgenes conferring complex traits.}, } @article {pmid29928301, year = {2018}, author = {Nygren, K and Dubey, M and Zapparata, A and Iqbal, M and Tzelepis, GD and Durling, MB and Jensen, DF and Karlsson, M}, title = {The mycoparasitic fungus Clonostachys rosea responds with both common and specific gene expression during interspecific interactions with fungal prey.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {931-949}, pmid = {29928301}, issn = {1752-4571}, abstract = {Clonostachys rosea is a necrotrophic mycoparasitic fungus, used for biological control of plant pathogenic fungi. A better understanding of the underlying mechanisms resulting in successful biocontrol is important for knowledge-based improvements of the application and use of biocontrol in agricultural production systems. Transcriptomic analyses revealed that C. rosea responded with both common and specific gene expression during interactions with the fungal prey species Botrytis cinerea and Fusarium graminearum. Genes predicted to encode proteins involved in membrane transport, biosynthesis of secondary metabolites and carbohydrate-active enzymes were induced during the mycoparasitic attack. Predicted major facilitator superfamily (MFS) transporters constituted 54% of the induced genes, and detailed phylogenetic and evolutionary analyses showed that a majority of these genes belonged to MFS gene families evolving under selection for increased paralog numbers, with predicted functions in drug resistance and transport of carbohydrates and small organic compounds. Sequence analysis of MFS transporters from family 2.A.1.3.65 identified rapidly evolving loop regions forming the entry to the transport tunnel, indicating changes in substrate specificity as a target for selection. Deletion of the MFS transporter gene mfs464 resulted in mutants with increased growth inhibitory activity against F. graminearum, providing evidence for a function in interspecific fungal interactions. In summary, we show that the mycoparasite C. rosea can distinguish between fungal prey species and modulate its transcriptomic responses accordingly. Gene expression data emphasize the importance of secondary metabolites in mycoparasitic interactions.}, } @article {pmid29928300, year = {2018}, author = {Bradbury, IR and Wringe, BF and Watson, B and Paterson, I and Horne, J and Beiko, R and Lehnert, SJ and Clément, M and Anderson, EC and Jeffery, NW and Duffy, S and Sylvester, E and Robertson, M and Bentzen, P}, title = {Genotyping-by-sequencing of genome-wide microsatellite loci reveals fine-scale harvest composition in a coastal Atlantic salmon fishery.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {918-930}, pmid = {29928300}, issn = {1752-4571}, abstract = {Individual assignment and genetic mixture analysis are commonly utilized in contemporary wildlife and fisheries management. Although microsatellite loci provide unparalleled numbers of alleles per locus, their use in assignment applications is increasingly limited. However, next-generation sequencing, in conjunction with novel bioinformatic tools, allows large numbers of microsatellite loci to be simultaneously genotyped, presenting new opportunities for individual assignment and genetic mixture analysis. Here, we scanned the published Atlantic salmon genome to identify 706 microsatellite loci, from which we developed a final panel of 101 microsatellites distributed across the genome (average 3.4 loci per chromosome). Using samples from 35 Atlantic salmon populations (n = 1,485 individuals) from coastal Labrador, Canada, a region characterized by low levels of differentiation in this species, this panel identified 844 alleles (average of 8.4 alleles per locus). Simulation-based evaluations of assignment and mixture identification accuracy revealed unprecedented resolution, clearly identifying 26 rivers or groups of rivers spanning 500 km of coastline. This baseline was used to examine the stock composition of 696 individuals harvested in the Labrador Atlantic salmon fishery and revealed that coastal fisheries largely targeted regional groups (<300 km). This work suggests that the development and application of large sequenced microsatellite panels presents great potential for stock resolution in Atlantic salmon and more broadly in other exploited anadromous and marine species.}, } @article {pmid29928299, year = {2018}, author = {Tran, TT and Janssens, L and Dinh, KV and Stoks, R}, title = {Transgenerational interactions between pesticide exposure and warming in a vector mosquito.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {906-917}, pmid = {29928299}, issn = {1752-4571}, abstract = {While transgenerational plasticity may buffer ectotherms to warming and pesticides separately, it remains unknown how combined exposure to warming and pesticides in the parental generation shapes the vulnerability to these stressors in the offspring. We studied the transgenerational effects of single and combined exposure to warming (4°C increase) and the pesticide chlorpyrifos on life-history traits of the vector mosquito Culex pipiens. Parental exposure to a single stressor, either warming or the pesticide, had negative effects on the offspring: parental exposure to both warming and the pesticide resulted in an overall lower offspring survival, and a delayed offspring metamorphosis. Parental exposure to a single stressor did, however, not alter the vulnerability of the offspring to the same stressor in terms of survival. Parental pesticide exposure resulted in larger offspring when the offspring experienced the same stressor as the parents. Within both the parental and offspring generations, warming made the pesticide more toxic in terms of survival. Yet, this synergism disappeared in the offspring of parents exposed to both stressors simultaneously because in this condition, the pesticide was already more lethal at the lower temperature. Our results indicate that transgenerational effects will not increase the ability of this vector species to deal with pesticides in a warming world. Bifactorial transgenerational experiments are crucial to understand the combined impact of warming and pesticides across generations, hence to assess the efficacy of vector control in a warming world.}, } @article {pmid29928298, year = {2018}, author = {Scott, R and Zhan, A and Brown, EA and Chain, FJJ and Cristescu, ME and Gras, R and MacIsaac, HJ}, title = {Optimization and performance testing of a sequence processing pipeline applied to detection of nonindigenous species.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {891-905}, pmid = {29928298}, issn = {1752-4571}, abstract = {Genetic taxonomic assignment can be more sensitive than morphological taxonomic assignment, particularly for small, cryptic or rare species. Sequence processing is essential to taxonomic assignment, but can also produce errors because optimal parameters are not known a priori. Here, we explored how sequence processing parameters influence taxonomic assignment of 18S sequences from bulk zooplankton samples produced by 454 pyrosequencing. We optimized a sequence processing pipeline for two common research goals, estimation of species richness and early detection of aquatic invasive species (AIS), and then tested most optimal models' performances through simulations. We tested 1,050 parameter sets on 18S sequences from 20 AIS to determine optimal parameters for each research goal. We tested optimized pipelines' performances (detectability and sensitivity) by computationally inoculating sequences of 20 AIS into ten bulk zooplankton samples from ports across Canada. We found that optimal parameter selection generally depends on the research goal. However, regardless of research goal, we found that metazoan 18S sequences produced by 454 pyrosequencing should be trimmed to 375-400 bp and sequence quality filtering should be relaxed (1.5 ≤ maximum expected error ≤ 3.0, Phred score = 10). Clustering and denoising were only viable for estimating species richness, because these processing steps made some species undetectable at low sequence abundances which would not be useful for early detection of AIS. With parameter sets optimized for early detection of AIS, 90% of AIS were detected with fewer than 11 target sequences, regardless of whether clustering or denoising was used. Despite developments in next-generation sequencing, sequence processing remains an important issue owing to difficulties in balancing false-positive and false-negative errors in metabarcoding data.}, } @article {pmid29928297, year = {2018}, author = {Yu, S}, title = {Uncovering the geographical and host impacts on the classification of Vibrio vulnificus.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {883-890}, pmid = {29928297}, issn = {1752-4571}, abstract = {Vibrio vulnificus causes human sickness throughout the world via the consumption of undercooked seafood or exposure to contaminated water. Previous attempts at phylogenetic analyses of V. vulnificus have proven unsuccessful, mainly due to the poorly understood impact of factors on its divergence. In this study, we used advanced statistical and phylogenetic methods to strengthen the classification of V. vulnificus. This updated classification included the impact of geographical and host factors. The results demonstrate the existence of hierarchies and multidimensional effects in the classification of V. vulnificus, from the molecular level using biotypes, to the distributional level using geographical location, to the adaptational level through host immune response. These findings have implications for the classification of bacteria, bacterial evolution, and public health.}, } @article {pmid29928296, year = {2018}, author = {Jeffery, NW and Bradbury, IR and Stanley, RRE and Wringe, BF and Van Wyngaarden, M and Lowen, JB and McKenzie, CH and Matheson, K and Sargent, PS and DiBacco, C}, title = {Genomewide evidence of environmentally mediated secondary contact of European green crab (Carcinus maenas) lineages in eastern North America.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {869-882}, pmid = {29928296}, issn = {1752-4571}, abstract = {Genetic-environment associations are increasingly revealed through population genomic data and can occur through a number of processes, including secondary contact, divergent natural selection, or isolation by distance. Here, we investigate the influence of the environment, including seasonal temperature and salinity, on the population structure of the invasive European green crab (Carcinus maenas) in eastern North America. Green crab populations in eastern North America are associated with two independent invasions, previously shown to consist of distinct northern and southern ecotypes, with a contact zone in southern Nova Scotia, Canada. Using a RAD-seq panel of 9,137 genomewide SNPs, we detected 41 SNPs (0.49%) whose allele frequencies were highly correlated with environmental data. A principal components analysis of 25 environmental variables differentiated populations into northern, southern, and admixed sites in concordance with the observed genomic spatial structure. Furthermore, a spatial principal components analysis conducted on genomic and geographic data revealed a high degree of global structure (p < .0001) partitioning a northern and southern ecotype. Redundancy and partial redundancy analyses revealed that among the environmental variables tested, winter sea surface temperature had the strongest association with spatial structuring, suggesting that it is an important factor defining range and expansion limits of each ecotype. Understanding environmental thresholds associated with intraspecific diversity will facilitate the ability to manage current and predict future distributions of this aquatic invasive species.}, } @article {pmid29928295, year = {2018}, author = {Waters, CD and Hard, JJ and Brieuc, MSO and Fast, DE and Warheit, KI and Knudsen, CM and Bosch, WJ and Naish, KA}, title = {Genomewide association analyses of fitness traits in captive-reared Chinook salmon: Applications in evaluating conservation strategies.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {853-868}, pmid = {29928295}, issn = {1752-4571}, abstract = {A novel application of genomewide association analyses is to use trait-associated loci to monitor the effects of conservation strategies on potentially adaptive genetic variation. Comparisons of fitness between captive- and wild-origin individuals, for example, do not reveal how captive rearing affects genetic variation underlying fitness traits or which traits are most susceptible to domestication selection. Here, we used data collected across four generations to identify loci associated with six traits in adult Chinook salmon (Oncorhynchus tshawytscha) and then determined how two alternative management approaches for captive rearing affected variation at these loci. Loci associated with date of return to freshwater spawning grounds (return timing), length and weight at return, age at maturity, spawn timing, and daily growth coefficient were identified using 9108 restriction site-associated markers and random forest, an approach suitable for polygenic traits. Mapping of trait-associated loci, gene annotations, and integration of results across multiple studies revealed candidate regions involved in several fitness-related traits. Genotypes at trait-associated loci were then compared between two hatchery populations that were derived from the same source but are now managed as separate lines, one integrated with and one segregated from the wild population. While no broad-scale change was detected across four generations, there were numerous regions where trait-associated loci overlapped with signatures of adaptive divergence previously identified in the two lines. Many regions, primarily with loci linked to return and spawn timing, were either unique to or more divergent in the segregated line, suggesting that these traits may be responding to domestication selection. This study is one of the first to utilize genomic approaches to demonstrate the effectiveness of a conservation strategy, managed gene flow, on trait-associated-and potentially adaptive-loci. The results will promote the development of trait-specific tools to better monitor genetic change in captive and wild populations.}, } @article {pmid29928294, year = {2018}, author = {Rosenheim, JA}, title = {Short- and long-term evolution in our arms race with cancer: Why the war on cancer is winnable.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {845-852}, pmid = {29928294}, issn = {1752-4571}, abstract = {Human society is engaged in an arms race against cancer, which pits one evolutionary process-human cultural evolution as we develop novel cancer therapies-against another evolutionary process-the ability of oncogenic selection operating among cancer cells to select for lineages that are resistant to our therapies. Cancer cells have a powerful ability to evolve resistance over the short term, leading to patient relapse following an initial period of apparent treatment efficacy. However, we are the beneficiaries of a fundamental asymmetry in our arms race against cancer: Whereas our cultural evolution is a long-term and continuous process, resistance evolution in cancer cells operates only over the short term and is discontinuous - all resistance adaptations are lost each time a cancer patient dies. Thus, our cultural adaptations are permanent, whereas cancer's genetic adaptations are ephemeral. Consequently, over the long term, there is good reason to expect that we will emerge as the winners in our war against cancer.}, } @article {pmid29928293, year = {2018}, author = {Vittecoq, M and Giraudeau, M and Sepp, T and Marcogliese, DJ and Klaassen, M and Renaud, F and Ujvari, B and Thomas, F}, title = {Turning natural adaptations to oncogenic factors into an ally in the war against cancer.}, journal = {Evolutionary applications}, volume = {11}, number = {6}, pages = {836-844}, pmid = {29928293}, issn = {1752-4571}, abstract = {Both field and experimental evolution studies have demonstrated that organisms naturally or artificially exposed to environmental oncogenic factors can, sometimes rapidly, evolve specific adaptations to cope with pollutants and their adverse effects on fitness. Although numerous pollutants are mutagenic and carcinogenic, little attention has been given to exploring the extent to which adaptations displayed by organisms living in oncogenic environments could inspire novel cancer treatments, through mimicking the processes allowing these organisms to prevent or limit malignant progression. Building on a substantial knowledge base from the literature, we here present and discuss this progressive and promising research direction, advocating closer collaboration between the fields of medicine, ecology, and evolution in the war against cancer.}, } @article {pmid29927707, year = {2018}, author = {Feurtey, A and Stukenbrock, EH}, title = {Interspecific Gene Exchange as a Driver of Adaptive Evolution in Fungi.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {377-398}, doi = {10.1146/annurev-micro-090817-062753}, pmid = {29927707}, issn = {1545-3251}, abstract = {Throughout evolutionary history in the kingdom Fungi, taxa have exchanged genetic information among species, as revealed in particular by analyses of genome sequences. In fungi, hybridization can occur by sexual mating or by fusion of vegetative structures giving rise to new species or leaving traces of introgression in the genome. Furthermore, gene exchange can occur by horizontal gene transfer between species and can even include organisms outside the kingdom Fungi. In several cases, interspecific gene exchange has been instrumental in rapid adaptive evolution of fungal species and has notably played a role in the emergence of new pathogens. Here we summarize mechanisms and examples of gene exchange in fungi with a particular focus on the genomic context. We emphasize the need for and potential of applying population genetic approaches to better understand the processes and the impact of interspecific gene exchange in rapid adaptive evolution and species diversification. The broad occurrence of gene exchange among fungal species challenges our species concepts in the kingdom Fungi.}, } @article {pmid29927706, year = {2018}, author = {Ost, KS and Round, JL}, title = {Communication Between the Microbiota and Mammalian Immunity.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {399-422}, doi = {10.1146/annurev-micro-090817-062307}, pmid = {29927706}, issn = {1545-3251}, abstract = {Mammalian immune systems evolved within a diverse world dominated by microbes, making interactions between these two life-forms inevitable. Adaptive immunity protects against microbes through antigen-specific responses. In classical studies, these responses were investigated in the context of pathogenicity; however, we now know that they have significant effects on our resident microbes. In turn, microbes employ an arsenal of mechanisms to influence development and specificity of host immunity. Understanding these complex reactions will be necessary to develop microbiota-based strategies to prevent or treat disease. Here we review the literature detailing the cross talk between resident microbes with a focus on the specificity of host responses and the microbial molecules that influence them.}, } @article {pmid29927705, year = {2018}, author = {Duraisingh, MT and Skillman, KM}, title = {Epigenetic Variation and Regulation in Malaria Parasites.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {355-375}, doi = {10.1146/annurev-micro-090817-062722}, pmid = {29927705}, issn = {1545-3251}, abstract = {Eukaryotic pathogens must survive in different hosts, respond to changing environments, and exploit specialized niches to propagate. Plasmodium parasites cause human malaria during bloodstream infections, where they must persist long enough to be transmitted. Parasites have evolved diverse strategies of variant gene expression that control critical biological processes of blood-stage infections, including antigenic variation, erythrocyte invasion, innate immune evasion, and nutrient acquisition, as well as life-cycle transitions. Epigenetic mechanisms within the parasite are being elucidated, with discovery of epigenomic marks associated with gene silencing and activation, and the identification of epigenetic regulators and chromatin proteins that are required for the switching and maintenance of gene expression. Here, we review the key epigenetic processes that facilitate transition through the parasite life cycle and epigenetic regulatory mechanisms utilized by Plasmodium parasites to survive changing environments and consider epigenetic switching in the context of the outcome of human infections.}, } @article {pmid29927369, year = {2018}, author = {Wei, Y and Mao, H and Xu, Y and Zou, W and Fang, J and Blom, J}, title = {Pseudomonas abyssi sp. nov., isolated from the abyssopelagic water of the Mariana Trench.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2462-2467}, doi = {10.1099/ijsem.0.002785}, pmid = {29927369}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Pacific Ocean ; Phosphatidylethanolamines ; Phospholipids/chemistry ; *Phylogeny ; Pseudomonas/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel heterotrophic, Gram-stain-negative, aerobic, rod-shaped bacterium, designated as strain MT5T, was isolated from deep seawater in the Mariana Trench and characterized phylogenetically and phenotypically. Bacterial optimal growth occurred at 28 °C (range, 4-45 °C), pH 5-7 (pH 4-11) and with 3-7 % (w/v) NaCl (0-18 %). Phylogenetic analysis based on 16S rRNA gene sequence showed that strain MT5T was related to members of the genus Pseudomonas and shared the highest sequence identities with Pseudomonas pachastrellae CCUG 46540T (99.6 %), Pseudomonas aestusnigri VGXO14T (98.5 %) and Pseudomonas oceani KX 20T (98.4 %). The 16S rRNA gene sequence identities between strain MT5T and other members of the genus Pseudomonas were below 96.7 %. The digital DNA-DNA hybridization values between strain MT5T and the two type strains, P. pachastrellae and P. aestusnigri, were 38.9±2.5 and 25.8±2.4 %, respectively. The average nucleotide identity values between strain MT5T and the two type strains were 90.3 and 87.0 %, respectively. Strain MT5T and the two type strains shared 94.98 and 86.2 % average amino acid identity, and 30 and 33 Karlin genomic signature, respectively. The sole respiratory menaquinone was Q-9. The major polar lipids were phosphatidylethanolamine, diphosphatidyglycerol and phosphatidylglycerol. The predominant cellular fatty acids of strain MT5T were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) (35.3 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (24.1 %), C16 : 0 (15.9 %) and C12 : 0 (7.2 %). The G+C content of the genomic DNA was 61.2 mol%. The combined genotypic and phenotypic data indicated that strain MT5T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas abyssi sp. nov. is proposed, with the type strain MT5T (=KCTC 62295T=MCCC 1K03351T).}, } @article {pmid29927368, year = {2018}, author = {Zhang, Q and Kanjanasuntree, R and Kim, JH and Yoon, JH and Sukhoom, A and Kantachote, D and Kim, W}, title = {Sphingomicrobium arenosum sp. nov., isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2551-2556}, doi = {10.1099/ijsem.0.002875}, pmid = {29927368}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Sphingomonadaceae/*classification/isolation & purification ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, strictly aerobic, motile by one single flagellum, dark-orange pigmented and rod-shaped bacterial strain, designated CAU 1457T, was isolated from marine sediment in the Republic of Korea and its taxonomic position was investigated by using a polyphasic approach. The isolate grew optimally at 30 °C, at pH 6.0 and in the presence of 2 % (w/v) NaCl. Based on 16S rRNA gene sequences similarity, strain CAU 1457T belonged to the genus Sphingomicrobium and was related most closely to Sphingomicrobium astaxanthinifaciens JCM 18551T (98.2 % similarity). Strain CAU 1457T contained ubiquinone-10 as the predominant isoprenoid quinone and 11-methyl C18 : 1ω7c and summed feature 8 (C18 : 1ω7c/ω6c) as the major cellular fatty acids. Triamine sym-homospermidine was detected as the major compound in the polyamine pattern. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, sphingoglycolipid, four unidentified glycolipids, one unidentified aminophospholipid, two unidentified phospholipids, one unidentified aminolipid and one unidentified lipid. DNA-DNA relatedness between strain CAU 1457T and the closely related strains, Sphingomicrobium astaxanthinifaciens JCM 18551T and Sphingomicrobium aestuariivivum KCTC 42286T were 32.7 and 28.4 %, respectively. The DNA G+C content of strain was 68.8 mol%. The phenotypic, chemotaxonomic and phylogenetic data indicated that strain CAU 1457T represents a novel species of the genus Sphingomicrobium, for which the name Sphingomicrobium arenosum sp. nov. is proposed. The type strain is CAU 1457T (=KCTC 62233T=NBRC 113094T).}, } @article {pmid29927367, year = {2018}, author = {Zhang, TY and Yu, Y and Zhu, H and Yang, SZ and Yang, TM and Zhang, MY and Zhang, YX}, title = {Absidia panacisoli sp. nov., isolated from rhizosphere of Panax notoginseng.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2468-2472}, doi = {10.1099/ijsem.0.002857}, pmid = {29927367}, issn = {1466-5034}, mesh = {Absidia/*classification/genetics/isolation & purification ; China ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Mycological Typing Techniques ; Panax notoginseng/*microbiology ; *Phylogeny ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A strain (SYPF 7183T) was isolated from rhizosphere soil of Panax notoginseng in southwest China. Phylogenetic analyses indicated that strain SYPF 7183T was distinct from the other Absidia species with well-supported values. Strain SYPF 7183T produced spherical or subpyriform sporangia and short cylindrical sporangiospores. The azygospores were globose to oval. Based on morphological and phylogenetic evidence, the novel strain Absidia panacisoli sp. nov. is proposed.}, } @article {pmid29927366, year = {2018}, author = {Zhang, LY and Ming, H and Zhao, ZL and Ji, WL and Salam, N and Jiao, JY and Fang, BZ and Li, WJ and Nie, GX}, title = {Nocardioides allogilvus sp. nov., a novel actinobacterium isolated from a karst cave.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2485-2490}, doi = {10.1099/ijsem.0.002863}, pmid = {29927366}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Caves/*microbiology ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A novel actinobacterium, designated strain CFH 30205T, was isolated from a soil sample collected from a karst cave in Luoyang, Henan Province, China. The taxonomic position of the strain was investigated by using a polyphasic approach. Cells of the strain were aerobic, Gram-stain-positive, non-motile and rod-shaped. The strain was found to be catalase- and oxidase-positive. Strain CFH 30205T grew optimally at 28 °C, pH 9.0 and in the presence of up to 1.5 % NaCl (w/v). On the basis of 16S rRNA gene sequence analysis, strain CFH 30205T was most closely related to the type strains of Nocardioides terrigena DS-17T (97.6 % sequence similarity) and Nocardioides sediminis MSL-01T (97.0 %). The DNA G+C content was determined to be 69.9 mol%. ll-2,6-Diaminopimelic acid was the diagnostic diamino acid in the cell-wall peptidoglycan. The whole-cell sugars were mannose, xylose and galactose. The major isoprenoid quinone was MK-8 (H4), and the major fatty acids (>10 %) were iso-C16 : 0 and anteiso-C14 : 0. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and an unidentified phospholipid. On the basis of phenotypic, genotypic and phylogenetic data, strain CFH 30205T merits representation of a novel species of the genus Nocardioides, for which the name Nocardioides allogilvus sp. nov. is proposed. The type strain is CFH 30205T (=KCTC 49020T=CGMCC 4.7457T).}, } @article {pmid29927365, year = {2018}, author = {Wei, Y and Wang, B and Zhang, L and Zhang, J and Chen, S}, title = {Pedobacter yulinensis sp. nov., isolated from sandy soil, and emended description of the genus Pedobacter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2523-2529}, doi = {10.1099/ijsem.0.002868}, pmid = {29927365}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Pedobacter/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-staining-negative, rod-shaped, strictly aerobic, non-motile, non-spore-forming, orange bacterium, which was designated strain YL28-9T, was isolated from sandy soil in the district of Yulin, Shaanxi province, PR China, and was characterized by using a polyphasic taxonomic approach. The optimal growth conditions of the strain were 30 °C, pH 7.0, 0 % (w/v) NaCl. Phylogenetic analysis, based on the 16S rRNA gene sequence, revealed that YL28-9T represented a member of the genus Pedobacter and showed the highest sequence similarity to Pedobacter rhizosphaeraeKACC 14938T (95.1 %). The genomic DNA G+C content of this strain was 50.4 mol%, which was out of the range reported for the other strains of members of the genus Pedobacter. The only respiratory quinone detected in YL28-9T was menaquinone-7 (MK-7). The predominant cellular fatty acids were identified as iso-C15 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and iso-C17 : 0 3-OH. The major polar lipid was phosphatidylethanolamine. On the basis of the results of phenotypic, genotypic, chemotaxonomic and phylogenetic analysis, YL28-9T could be distinguished from the most closely related species of the genus Pedobacter. It is evident from the derived data that YL28-9T represents a novel species of the genus Pedobacter,for which the name Pedobacter yulinensis sp. nov. is proposed. The type strain is YL28-9T (=CGMCC 1.16050T=KCTC 62104T). An emended description of the genus Pedobacteris proposed.}, } @article {pmid29927061, year = {2018}, author = {Stevens, M and Ruxton, GD}, title = {The key role of behaviour in animal camouflage.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12438}, pmid = {29927061}, issn = {1469-185X}, abstract = {Animal camouflage represents one of the most important ways of preventing (or facilitating) predation. It attracted the attention of the earliest evolutionary biologists, and today remains a focus of investigation in areas ranging from evolutionary ecology, animal decision-making, optimal strategies, visual psychology, computer science, to materials science. Most work focuses on the role of animal morphology per se, and its interactions with the background in affecting detection and recognition. However, the behaviour of organisms is likely to be crucial in affecting camouflage too, through background choice, body orientation and positioning; and strategies of camouflage that require movement. A wealth of potential mechanisms may affect such behaviours, from imprinting and self-assessment to genetics, and operate at several levels (species, morph, and individual). Over many years there have been numerous studies investigating the role of behaviour in camouflage, but to date, no effort to synthesise these studies and ideas into a coherent framework. Here, we review key work on behaviour and camouflage, highlight the mechanisms involved and implications of behaviour, discuss the importance of this in a changing world, and offer suggestions for addressing the many important gaps in our understanding of this subject.}, } @article {pmid29927019, year = {2018}, author = {Brom, T and Massot, M and Laloi, D}, title = {The sex chromosome system can influence the evolution of sex-biased dispersal.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1377-1385}, doi = {10.1111/jeb.13340}, pmid = {29927019}, issn = {1420-9101}, abstract = {Sex-biased dispersal is a much-discussed feature in literature on dispersal. Diverse hypotheses have been proposed to explain the evolution of sex-biased dispersal, a difference in dispersal rate or dispersal distance between males and females. An early hypothesis has indicated that it may rely on the difference in sex chromosomes between males and females. However, this proposal was quickly rejected without a real assessment. We propose a new perspective on this hypothesis by investigating the evolution of sex-biased dispersal when dispersal genes are sex-linked, that is when they are located on the sex chromosomes. We show that individuals of the heterogametic sex disperse relatively more than do individuals of the homogametic sex when dispersal genes are sex-linked rather than autosomal. Although such a sex-biased dispersal towards the heterogametic sex is always observed in monogamous species, the mating system and the location of dispersal genes interact to modulate sex-biased dispersal in monandry and polyandry. In the context of the multicausality of dispersal, we suggest that sex-linked dispersal genes can influence the evolution of sex-biased dispersal.}, } @article {pmid29927015, year = {2018}, author = {Karve, SM and Bhave, D and Dey, S}, title = {Extent of adaptation is not limited by unpredictability of the environment in laboratory populations of Escherichia coli.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1420-1426}, doi = {10.1111/jeb.13338}, pmid = {29927015}, issn = {1420-9101}, support = {//Senior Research Fellowship from Council of Scientific and Industrial Research, Govt. of India/ ; BT/PR5655/BRB/10/1088/2012//Department of Biotechnology, Government of India/ ; //Indian Institute of Science Education and Research, Pune/ ; }, abstract = {Environmental variability is on the rise in different parts of the earth, and the survival of many species depends on how well they cope with these fluctuations. Our current understanding of how organisms adapt to unpredictably fluctuating environments is almost entirely based on studies that investigate fluctuations among different values of a single environmental stressor such as temperature or pH. How would unpredictability affect adaptation when the environment fluctuates between qualitatively very different kinds of stresses? To answer this question, we subjected laboratory populations of Escherichia coli to selection over ~ 260 generations. The populations faced predictable and unpredictable environmental fluctuations across qualitatively different selection environments, namely, salt and acidic pH. We show that predictability of environmental fluctuations does not play a role in determining the extent of adaptation, although the extent of ancestral adaptation to the chosen selection environments is of key importance.}, } @article {pmid29927009, year = {2018}, author = {Lucek, K and Keller, I and Nolte, AW and Seehausen, O}, title = {Distinct colonization waves underlie the diversification of the freshwater sculpin (Cottus gobio) in the Central European Alpine region.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1254-1267}, doi = {10.1111/jeb.13339}, pmid = {29927009}, issn = {1420-9101}, support = {P2BEP3_152103//SNSF/ ; 31003A_166322//SNSF/ ; }, abstract = {Ecological speciation and adaptive radiation are key processes shaping northern temperate freshwater fish diversity. Both often involve parapatric differentiation between stream and lake populations and less often, sympatric intralacustrine diversification into habitat- and resource-associated ecotypes. However, few taxa have been studied, calling for studies of others to investigate the generality of these processes. Here, we test for diversification within catchments in freshwater sculpins in a network of peri-Alpine lakes and streams. Using 8047 and 13 182 restriction site-associated (RADseq) SNPs, respectively, we identify three deeply divergent phylogeographic lineages associated with different major European drainages. Within the Aare catchment, we observe populations from geographically distant lakes to be genetically more similar to each other than to populations from nearby streams. This pattern is consistent with two distinct colonization waves, rather than by parapatric ecological speciation after a single colonization wave. We further find two distinct depth distribution modes in three lakes of the Aare catchment, one in very shallow and one in very deep water, and significant genomewide differentiation between these in one lake. Sculpins in the Aare catchment appear to represent an early-stage adaptive radiation involving the evolution of a lacustrine lineage distinct from parapatric stream sculpins and the repeated onset of depth-related intralacustrine differentiation.}, } @article {pmid29927003, year = {2018}, author = {Moore, MP and Lis, C and Martin, RA}, title = {Immune deployment increases larval vulnerability to predators and inhibits adult life-history traits in a dragonfly.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1365-1376}, doi = {10.1111/jeb.13337}, pmid = {29927003}, issn = {1420-9101}, support = {//GAANN Fellowship/ ; }, abstract = {While deploying immune defences early in ontogeny can trade-off with the production and maintenance of other important traits across the entire life cycle, it remains largely unexplored how features of the environment shape the magnitude or presence of these lifetime costs. Greater predation risk during the juvenile stage may particularly influence such costs by (1) magnifying the survival costs that arise from any handicap of juvenile avoidance traits and/or (2) intensifying allocation trade-offs with important adult traits. Here, we tested for predator-dependent costs of immune deployment within and across life stages using the dragonfly, Pachydiplax longipennis. We first examined how larval immune deployment affected two traits associated with larval vulnerability to predators: escape distance and foraging under predation risk. Larvae that were induced to mount an immune response had shorter escape distances but lower foraging activity in the presence of predator cues. We also induced immune responses in larvae and reared them through emergence in mesocosms that differed in the presence of large predatory dragonfly larvae (Aeshnidae spp.). Immune-challenged larvae had later emergence overall and lower survival in pools with predators. Immune-challenged males were also smaller at emergence and developed less sexually selected melanin wing coloration, but these effects were independent of predator treatment. Overall, these results highlight how mounting an immune defence early in ontogeny can have substantial ecological and physiological costs that manifest both within and across life stages.}, } @article {pmid29926914, year = {2018}, author = {Denton, RD and Morales, AE and Gibbs, HL}, title = {Genome-specific histories of divergence and introgression between an allopolyploid unisexual salamander lineage and two ancestral sexual species.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13528}, pmid = {29926914}, issn = {1558-5646}, abstract = {Quantifying introgression between sexual species and polyploid lineages traditionally thought to be asexual is an important step in understanding what drives the longevity of putatively asexual groups. Here, we capitalize on three recent innovations-ultraconserved element (UCE) sequencing, bioinformatic techniques for identifying genome-specific variation in polyploids, and model-based methods for evaluating historical gene flow-to measure the extent and tempo of introgression over the evolutionary history of an allopolyploid lineage of all-female salamanders and two ancestral sexual species. Our analyses support a scenario in which the genomes sampled in unisexual salamanders last shared a common ancestor with genomes in their parental species ∼3.4 million years ago, followed by a period of divergence between homologous genomes. Recently, secondary introgression has occurred at different times with each sexual species during the last 500,000 years. Sustained introgression of sexual genomes into the unisexual lineage is the defining characteristic of their reproductive mode, but this study provides the first evidence that unisexual genomes have undergone long periods of divergence without introgression. Unlike other sperm-dependent taxa in which introgression is rare, the alternating periods of divergence and introgression between unisexual salamanders and their sexual relatives could explain why these salamanders are among the oldest described unisexual animals.}, } @article {pmid29926120, year = {2018}, author = {Hart, MLI and Vu, BL and Bolden, Q and Chen, KT and Oakes, CL and Zoronjic, L and Meisel, RP}, title = {Genes Relocated Between Drosophila Chromosome Arms Evolve Under Relaxed Selective Constraints Relative to Non-Relocated Genes.}, journal = {Journal of molecular evolution}, volume = {}, number = {}, pages = {}, pmid = {29926120}, issn = {1432-1432}, abstract = {Gene duplication creates a second copy of a gene either in tandem to the ancestral locus or dispersed to another chromosomal location. When the ancestral copy of a dispersed duplicate is lost from the genome, it creates the appearance that the gene was "relocated" from the ancestral locus to the derived location. Gene relocations may be as common as canonical dispersed duplications in which both the ancestral and derived copies are retained. Relocated genes appear to be under more selective constraints than the derived copies of canonical duplications, and they are possibly as conserved as single-copy non-relocated genes. To test this hypothesis, we combined comparative genomics, population genetics, gene expression, and functional analyses to assess the selection pressures acting on relocated, duplicated, and non-relocated single-copy genes in Drosophila genomes. We find that relocated genes evolve faster than single-copy non-relocated genes, and there is no evidence that this faster evolution is driven by positive selection. In addition, relocated genes are less essential for viability and male fertility than single-copy non-relocated genes, suggesting that relocated genes evolve fast because of relaxed selective constraints. However, relocated genes evolve slower than the derived copies of canonical dispersed duplicated genes. We therefore conclude that relocated genes are under more selective constraints than canonical duplicates, but are not as conserved as single-copy non-relocated genes.}, } @article {pmid29925979, year = {2018}, author = {}, title = {Mars storm, AI ethics and the LHC's big upgrade.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {348-349}, doi = {10.1038/d41586-018-05468-4}, pmid = {29925979}, issn = {1476-4687}, } @article {pmid29925978, year = {2018}, author = {Donnelly, CA and Boyd, I and Campbell, P and Craig, C and Vallance, P and Walport, M and Whitty, CJM and Woods, E and Wormald, C}, title = {Four principles to make evidence synthesis more useful for policy.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {361-364}, doi = {10.1038/d41586-018-05414-4}, pmid = {29925978}, issn = {1476-4687}, mesh = {Administrative Personnel ; Advisory Committees/*organization & administration ; Animals ; Child ; Humans ; Pediatric Obesity ; *Policy Making ; *Science ; Time Factors ; }, } @article {pmid29925977, year = {2018}, author = {Sutherland, WJ and Wordley, CFR}, title = {A fresh approach to evidence synthesis.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {364-366}, doi = {10.1038/d41586-018-05472-8}, pmid = {29925977}, issn = {1476-4687}, mesh = {Animals ; Conservation of Natural Resources/economics ; Cost-Benefit Analysis ; Evidence-Based Practice/economics/*trends ; Humans ; *Policy Making ; Time Factors ; }, } @article {pmid29925976, year = {2018}, author = {}, title = {Evidence synthesis needs greater incentives.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {344}, doi = {10.1038/d41586-018-05464-8}, pmid = {29925976}, issn = {1476-4687}, mesh = {*Motivation ; *Policy ; }, } @article {pmid29925975, year = {2018}, author = {}, title = {Nature's under-representation of women.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {344}, doi = {10.1038/d41586-018-05465-7}, pmid = {29925975}, issn = {1476-4687}, mesh = {Female ; Humans ; *Sexism ; }, } @article {pmid29925973, year = {2018}, author = {Courtland, R}, title = {Bias detectives: the researchers striving to make algorithms fair.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {357-360}, doi = {10.1038/d41586-018-05469-3}, pmid = {29925973}, issn = {1476-4687}, mesh = {*Algorithms ; Bias ; Machine Learning/*ethics/standards ; Research Personnel/*ethics ; *Social Justice ; *Truth Disclosure ; }, } @article {pmid29925972, year = {2018}, author = {Fang, T}, title = {Missing matter found in the cosmic web.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {375-376}, doi = {10.1038/d41586-018-05432-2}, pmid = {29925972}, issn = {1476-4687}, mesh = {Astronomical Phenomena ; *Astronomy ; *Elementary Particles ; }, } @article {pmid29925971, year = {2018}, author = {Duan, C}, title = {Frictionless gas flow observed in perfectly flat-walled nanochannels.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {379-380}, doi = {10.1038/d41586-018-05403-7}, pmid = {29925971}, issn = {1476-4687}, mesh = {Biological Transport ; *Nanotechnology ; }, } @article {pmid29925970, year = {2018}, author = {Bediako, DK and Rezaee, M and Yoo, H and Larson, DT and Zhao, SYF and Taniguchi, T and Watanabe, K and Brower-Thomas, TL and Kaxiras, E and Kim, P}, title = {Heterointerface effects in the electrointercalation of van der Waals heterostructures.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {425-429}, doi = {10.1038/s41586-018-0205-0}, pmid = {29925970}, issn = {1476-4687}, abstract = {Molecular-scale manipulation of electronic and ionic charge accumulation in materials is the backbone of electrochemical energy storage1-4. Layered van der Waals (vdW) crystals are a diverse family of materials into which mobile ions can electrochemically intercalate into the interlamellar gaps of the host atomic lattice5,6. The structural diversity of such materials enables the interfacial properties of composites to be optimized to improve ion intercalation for energy storage and electronic devices7-12. However, the ability of heterolayers to modify intercalation reactions, and their role at the atomic level, are yet to be elucidated. Here we demonstrate the electrointercalation of lithium at the level of individual atomic interfaces of dissimilar vdW layers. Electrochemical devices based on vdW heterostructures 13 of stacked hexagonal boron nitride, graphene and molybdenum dichalcogenide (MoX2; X = S, Se) layers are constructed. We use transmission electron microscopy, in situ magnetoresistance and optical spectroscopy techniques, as well as low-temperature quantum magneto-oscillation measurements and ab initio calculations, to resolve the intermediate stages of lithium intercalation at heterointerfaces. The formation of vdW heterointerfaces between graphene and MoX2 results in a more than tenfold greater accumulation of charge in MoX2 when compared to MoX2/MoX2 homointerfaces, while enforcing a more negative intercalation potential than that of bulk MoX2 by at least 0.5 V. Beyond energy storage, our combined experimental and computational methodology for manipulating and characterizing the electrochemical behaviour of layered systems opens new pathways to control the charge density in two-dimensional electronic and optoelectronic devices.}, } @article {pmid29925969, year = {2018}, author = {Nicastro, F and Kaastra, J and Krongold, Y and Borgani, S and Branchini, E and Cen, R and Dadina, M and Danforth, CW and Elvis, M and Fiore, F and Gupta, A and Mathur, S and Mayya, D and Paerels, F and Piro, L and Rosa-Gonzalez, D and Schaye, J and Shull, JM and Torres-Zafra, J and Wijers, N and Zappacosta, L}, title = {Observations of the missing baryons in the warm-hot intergalactic medium.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {406-409}, doi = {10.1038/s41586-018-0204-1}, pmid = {29925969}, issn = {1476-4687}, abstract = {It has been known for decades that the observed number of baryons in the local Universe falls about 30-40 per cent short1,2 of the total number of baryons predicted 3 by Big Bang nucleosynthesis, as inferred4,5 from density fluctuations of the cosmic microwave background and seen during the first 2-3 billion years of the Universe in the so-called 'Lyman α forest'6,7 (a dense series of intervening H I Lyman α absorption lines in the optical spectra of background quasars). A theoretical solution to this paradox locates the missing baryons in the hot and tenuous filamentary gas between galaxies, known as the warm-hot intergalactic medium. However, it is difficult to detect them there because the largest by far constituent of this gas-hydrogen-is mostly ionized and therefore almost invisible in far-ultraviolet spectra with typical signal-to-noise ratios8,9. Indeed, despite large observational efforts, only a few marginal claims of detection have been made so far2,10. Here we report observations of two absorbers of highly ionized oxygen (O VII) in the high-signal-to-noise-ratio X-ray spectrum of a quasar at a redshift higher than 0.4. These absorbers show no variability over a two-year timescale and have no associated cold absorption, making the assumption that they originate from the quasar's intrinsic outflow or the host galaxy's interstellar medium implausible. The O VII systems lie in regions characterized by large (four times larger than average 11) galaxy overdensities and their number (down to the sensitivity threshold of our data) agrees well with numerical simulation predictions for the long-sought warm-hot intergalactic medium. We conclude that the missing baryons have been found.}, } @article {pmid29925968, year = {2018}, author = {Keerthi, A and Geim, AK and Janardanan, A and Rooney, AP and Esfandiar, A and Hu, S and Dar, SA and Grigorieva, IV and Haigh, SJ and Wang, FC and Radha, B}, title = {Ballistic molecular transport through two-dimensional channels.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {420-424}, doi = {10.1038/s41586-018-0203-2}, pmid = {29925968}, issn = {1476-4687}, abstract = {Gas permeation through nanoscale pores is ubiquitous in nature and has an important role in many technologies1,2. Because the pore size is typically smaller than the mean free path of gas molecules, the flow of the gas molecules is conventionally described by Knudsen theory, which assumes diffuse reflection (random-angle scattering) at confining walls3-7. This assumption holds surprisingly well in experiments, with only a few cases of partially specular (mirror-like) reflection known5,8-11. Here we report gas transport through ångström-scale channels with atomically flat walls12,13 and show that surface scattering can be either diffuse or specular, depending on the fine details of the atomic landscape of the surface, and that quantum effects contribute to the specularity at room temperature. The channels, made from graphene or boron nitride, allow helium gas flow that is orders of magnitude faster than expected from theory. This is explained by specular surface scattering, which leads to ballistic transport and frictionless gas flow. Similar channels, but with molybdenum disulfide walls, exhibit much slower permeation that remains well described by Knudsen diffusion. We attribute the difference to the larger atomic corrugations at molybdenum disulfide surfaces, which are similar in height to the size of the atoms being transported and their de Broglie wavelength. The importance of this matter-wave contribution is corroborated by the observation of a reversed isotope effect, whereby the mass flow of hydrogen is notably higher than that of deuterium, in contrast to the relation expected for classical flows. Our results provide insights into the atomistic details of molecular permeation, which previously could be accessed only in simulations10,14, and demonstrate the possibility of studying gas transport under controlled confinement comparable in size to the quantum-mechanical size of atoms.}, } @article {pmid29925961, year = {2018}, author = {Koch, L}, title = {What makes us human?.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {472}, doi = {10.1038/s41576-018-0029-7}, pmid = {29925961}, issn = {1471-0064}, } @article {pmid29925958, year = {2018}, author = {Vo, MN and Terrey, M and Lee, JW and Roy, B and Moresco, JJ and Sun, L and Fu, H and Liu, Q and Weber, TG and Yates, JR and Fredrick, K and Schimmel, P and Ackerman, SL}, title = {Publisher Correction: ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {E35}, doi = {10.1038/s41586-018-0271-3}, pmid = {29925958}, issn = {1476-4687}, abstract = {In the Fig. 3b western blot of this Article, 'Myc-AlaRS' in row one should have been 'Myc-AAD Aars', 'AlaRS' in row two should have been 'Aars' and 'ANKRD16' in row four should have been 'Ankrd16'. In Fig. 4f, 'ANKRD16' and 'ANKRD16(3xR)' should have been 'Ankrd16' and 'Ankrd163xR; and in Fig. 3c the position of the molecular mass markers had shifted. These figures have been corrected online, and see Supplementary Information to the accompanying Amendment for the original figure.}, } @article {pmid29925957, year = {2018}, author = {Wu, J and Xu, J and Liu, B and Yao, G and Wang, P and Lin, Z and Huang, B and Wang, X and Li, T and Shi, S and Zhang, N and Duan, F and Ming, J and Zhang, X and Niu, W and Song, W and Jin, H and Guo, Y and Dai, S and Hu, L and Fang, L and Wang, Q and Li, Y and Li, W and Na, J and Xie, W and Sun, Y}, title = {Publisher Correction: Chromatin analysis in human early development reveals epigenetic transition during ZGA.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {E27}, doi = {10.1038/s41586-018-0267-z}, pmid = {29925957}, issn = {1476-4687}, abstract = {In this Letter, the 'Open chromatin' label in Fig. 4a should have been centred above the first three columns, and the black horizontal line underneath the label should have been removed. In addition, there should have been a vertical black line between the last two sets of panels for consistency. Minor changes have also been made to Fig. 1 and to the legend of Fig. 3. These errrors have been corrected online, and see Supplementary Information to the accompanying Amendment for the original Fig. 4.}, } @article {pmid29925956, year = {2018}, author = {Zhou, Q and Melton, DA}, title = {Author Correction: Pancreas regeneration.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {E34}, doi = {10.1038/s41586-018-0294-9}, pmid = {29925956}, issn = {1476-4687}, abstract = {Change history: In this Insight Review, '1989' has been changed to '1998' in the sentence "This deep understanding of pancreatic development was put to the service of regenerative medicine in 1998, when human embryonic stem cells (hES cells) were successfully cultured and opened the door to developing methods of deriving pancreatic islets from hES cells66.". This error has been corrected online.}, } @article {pmid29925955, year = {2018}, author = {Phelan, JD and Young, RM and Webster, DE and Roulland, S and Wright, GW and Kasbekar, M and Shaffer, AL and Ceribelli, M and Wang, JQ and Schmitz, R and Nakagawa, M and Bachy, E and Huang, DW and Ji, Y and Chen, L and Yang, Y and Zhao, H and Yu, X and Xu, W and Palisoc, MM and Valadez, RR and Davies-Hill, T and Wilson, WH and Chan, WC and Jaffe, ES and Gascoyne, RD and Campo, E and Rosenwald, A and Ott, G and Delabie, J and Rimsza, LM and Rodriguez, FJ and Estephan, F and Holdhoff, M and Kruhlak, MJ and Hewitt, SM and Thomas, CJ and Pittaluga, S and Oellerich, T and Staudt, LM}, title = {A multiprotein supercomplex controlling oncogenic signalling in lymphoma.}, journal = {Nature}, volume = {560}, number = {7718}, pages = {387-391}, pmid = {29925955}, issn = {1476-4687}, support = {U01 CA157581/CA/NCI NIH HHS/United States ; Z01 BC011008-01//NULL/International ; }, abstract = {B cell receptor (BCR) signalling has emerged as a therapeutic target in B cell lymphomas, but inhibiting this pathway in diffuse large B cell lymphoma (DLBCL) has benefited only a subset of patients1. Gene expression profiling identified two major subtypes of DLBCL, known as germinal centre B cell-like and activated B cell-like (ABC)2,3, that show poor outcomes after immunochemotherapy in ABC. Autoantigens drive BCR-dependent activation of NF-κB in ABC DLBCL through a kinase signalling cascade of SYK, BTK and PKCβ to promote the assembly of the CARD11-BCL10-MALT1 adaptor complex, which recruits and activates IκB kinase4-6. Genome sequencing revealed gain-of-function mutations that target the CD79A and CD79B BCR subunits and the Toll-like receptor signalling adaptor MYD885,7, with MYD88(L265P) being the most prevalent isoform. In a clinical trial, the BTK inhibitor ibrutinib produced responses in 37% of cases of ABC1. The most striking response rate (80%) was observed in tumours with both CD79B and MYD88(L265P) mutations, but how these mutations cooperate to promote dependence on BCR signalling remains unclear. Here we used genome-wide CRISPR-Cas9 screening and functional proteomics to determine the molecular basis of exceptional clinical responses to ibrutinib. We discovered a new mode of oncogenic BCR signalling in ibrutinib-responsive cell lines and biopsies, coordinated by a multiprotein supercomplex formed by MYD88, TLR9 and the BCR (hereafter termed the My-T-BCR supercomplex). The My-T-BCR supercomplex co-localizes with mTOR on endolysosomes, where it drives pro-survival NF-κB and mTOR signalling. Inhibitors of BCR and mTOR signalling cooperatively decreased the formation and function of the My-T-BCR supercomplex, providing mechanistic insight into their synergistic toxicity for My-T-BCR+ DLBCL cells. My-T-BCR supercomplexes characterized ibrutinib-responsive malignancies and distinguished ibrutinib responders from non-responders. Our data provide a framework for the rational design of oncogenic signalling inhibitors in molecularly defined subsets of DLBCL.}, } @article {pmid29925954, year = {2018}, author = {Evans, DA and Stempel, AV and Vale, R and Ruehle, S and Lefler, Y and Branco, T}, title = {A synaptic threshold mechanism for computing escape decisions.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {590-594}, pmid = {29925954}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; 098400//Wellcome Trust/United Kingdom ; MC_UP_1201/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Calcium/analysis ; *Decision Making ; Escape Reaction/*physiology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; *Models, Neurological ; Neural Pathways ; Optogenetics ; Periaqueductal Gray/physiology ; Superior Colliculi/physiology ; Synapses/*metabolism ; }, abstract = {Escaping from imminent danger is an instinctive behaviour that is fundamental for survival, and requires the classification of sensory stimuli as harmless or threatening. The absence of threat enables animals to forage for essential resources, but as the level of threat and potential for harm increases, they have to decide whether or not to seek safety 1 . Despite previous work on instinctive defensive behaviours in rodents2-11, little is known about how the brain computes the threat level for initiating escape. Here we show that the probability and vigour of escape in mice scale with the saliency of innate threats, and are well described by a model that computes the distance between the threat level and an escape threshold. Calcium imaging and optogenetics in the midbrain of freely behaving mice show that the activity of excitatory neurons in the deep layers of the medial superior colliculus (mSC) represents the saliency of the threat stimulus and is predictive of escape, whereas glutamatergic neurons of the dorsal periaqueductal grey (dPAG) encode exclusively the choice to escape and control escape vigour. We demonstrate a feed-forward monosynaptic excitatory connection from mSC to dPAG neurons, which is weak and unreliable-yet required for escape behaviour-and provides a synaptic threshold for dPAG activation and the initiation of escape. This threshold can be overcome by high mSC network activity because of short-term synaptic facilitation and recurrent excitation within the mSC, which amplifies and sustains synaptic drive to the dPAG. Therefore, dPAG glutamatergic neurons compute escape decisions and escape vigour using a synaptic mechanism to threshold threat information received from the mSC, and provide a biophysical model of how the brain performs a critical behavioural computation.}, } @article {pmid29925953, year = {2018}, author = {Rapino, F and Delaunay, S and Rambow, F and Zhou, Z and Tharun, L and De Tullio, P and Sin, O and Shostak, K and Schmitz, S and Piepers, J and Ghesquière, B and Karim, L and Charloteaux, B and Jamart, D and Florin, A and Lambert, C and Rorive, A and Jerusalem, G and Leucci, E and Dewaele, M and Vooijs, M and Leidel, SA and Georges, M and Voz, M and Peers, B and Büttner, R and Marine, JC and Chariot, A and Close, P}, title = {Codon-specific translation reprogramming promotes resistance to targeted therapy.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {605-609}, doi = {10.1038/s41586-018-0243-7}, pmid = {29925953}, issn = {1476-4687}, mesh = {Animals ; Carrier Proteins/chemistry/metabolism ; Cell Line, Tumor ; Codon/drug effects/*genetics ; Drug Resistance, Neoplasm/*drug effects/*genetics ; Female ; Humans ; Male ; Mechanistic Target of Rapamycin Complex 2/metabolism ; Melanoma/*drug therapy/*genetics/pathology ; Melanoma, Experimental/drug therapy/genetics/pathology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Phosphorylation ; *Protein Biosynthesis/drug effects ; Proto-Oncogene Proteins B-raf/antagonists & inhibitors/genetics ; RNA, Messenger/genetics/metabolism ; RNA, Transfer/chemistry/genetics/metabolism ; Signal Transduction ; Uridine/chemistry/genetics/metabolism ; Vemurafenib/pharmacology/therapeutic use ; Zebrafish/genetics ; }, abstract = {Reprogramming of mRNA translation has a key role in cancer development and drug resistance 1 . However, the molecular mechanisms that are involved in this process remain poorly understood. Wobble tRNA modifications are required for specific codon decoding during translation2,3. Here we show, in humans, that the enzymes that catalyse modifications of wobble uridine 34 (U34) tRNA (U34 enzymes) are key players of the protein synthesis rewiring that is induced by the transformation driven by the BRAF V600E oncogene and by resistance to targeted therapy in melanoma. We show that BRAF V600E -expressing melanoma cells are dependent on U34 enzymes for survival, and that concurrent inhibition of MAPK signalling and ELP3 or CTU1 and/or CTU2 synergizes to kill melanoma cells. Activation of the PI3K signalling pathway, one of the most common mechanisms of acquired resistance to MAPK therapeutic agents, markedly increases the expression of U34 enzymes. Mechanistically, U34 enzymes promote glycolysis in melanoma cells through the direct, codon-dependent, regulation of the translation of HIF1A mRNA and the maintenance of high levels of HIF1α protein. Therefore, the acquired resistance to anti-BRAF therapy is associated with high levels of U34 enzymes and HIF1α. Together, these results demonstrate that U34 enzymes promote the survival and resistance to therapy of melanoma cells by regulating specific mRNA translation.}, } @article {pmid29925952, year = {2018}, author = {Gizzi, AS and Grove, TL and Arnold, JJ and Jose, J and Jangra, RK and Garforth, SJ and Du, Q and Cahill, SM and Dulyaninova, NG and Love, JD and Chandran, K and Bresnick, AR and Cameron, CE and Almo, SC}, title = {A naturally occurring antiviral ribonucleotide encoded by the human genome.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {610-614}, pmid = {29925952}, issn = {1476-4687}, support = {P01 CA100324/CA/NCI NIH HHS/United States ; P01 GM118303/GM/NIGMS NIH HHS/United States ; R21 AI133329/AI/NIAID NIH HHS/United States ; R01 AI045818/AI/NIAID NIH HHS/United States ; U54 GM094662/GM/NIGMS NIH HHS/United States ; U54 GM093342/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antiviral Agents/chemistry/*metabolism ; Cercopithecus aethiops ; Cytidine Triphosphate/*analogs & derivatives/chemistry/*metabolism ; Genome, Human/*genetics ; HEK293 Cells ; Humans ; Proteins/*genetics/*metabolism ; RNA Replicase/antagonists & inhibitors/metabolism ; Substrate Specificity ; *Transcription Termination, Genetic ; Vero Cells ; Zika Virus/enzymology/metabolism ; }, abstract = {Viral infections continue to represent major challenges to public health, and an enhanced mechanistic understanding of the processes that contribute to viral life cycles is necessary for the development of new therapeutic strategies 1 . Viperin, a member of the radical S-adenosyl-L-methionine (SAM) superfamily of enzymes, is an interferon-inducible protein implicated in the inhibition of replication of a broad range of RNA and DNA viruses, including dengue virus, West Nile virus, hepatitis C virus, influenza A virus, rabies virus 2 and HIV3,4. Viperin has been suggested to elicit these broad antiviral activities through interactions with a large number of functionally unrelated host and viral proteins3,4. Here we demonstrate that viperin catalyses the conversion of cytidine triphosphate (CTP) to 3'-deoxy-3',4'-didehydro-CTP (ddhCTP), a previously undescribed biologically relevant molecule, via a SAM-dependent radical mechanism. We show that mammalian cells expressing viperin and macrophages stimulated with IFNα produce substantial quantities of ddhCTP. We also establish that ddhCTP acts as a chain terminator for the RNA-dependent RNA polymerases from multiple members of the Flavivirus genus, and show that ddhCTP directly inhibits replication of Zika virus in vivo. These findings suggest a partially unifying mechanism for the broad antiviral effects of viperin that is based on the intrinsic enzymatic properties of the protein and involves the generation of a naturally occurring replication-chain terminator encoded by mammalian genomes.}, } @article {pmid29925951, year = {2018}, author = {García-Nafría, J and Nehmé, R and Edwards, PC and Tate, CG}, title = {Cryo-EM structure of the serotonin 5-HT1B receptor coupled to heterotrimeric Go.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {620-623}, pmid = {29925951}, issn = {1476-4687}, support = {339995//European Research Council/International ; MC_U105197215//Medical Research Council/United Kingdom ; }, mesh = {*Cryoelectron Microscopy ; GTP-Binding Protein alpha Subunits, Gi-Go/chemistry/*metabolism/*ultrastructure ; GTP-Binding Protein alpha Subunits, Gs/chemistry/metabolism ; Humans ; Models, Molecular ; Nitriles/chemistry/metabolism ; Piperazines/chemistry/metabolism ; Protein Conformation ; Receptor, Serotonin, 5-HT1B/chemistry/*metabolism/*ultrastructure ; Serotonin 5-HT1 Receptor Agonists/chemistry/metabolism ; Tryptamines/chemistry/metabolism ; }, abstract = {G-protein-coupled receptors (GPCRs) form the largest family of receptors encoded by the human genome (around 800 genes). They transduce signals by coupling to a small number of heterotrimeric G proteins (16 genes encoding different α-subunits). Each human cell contains several GPCRs and G proteins. The structural determinants of coupling of Gs to four different GPCRs have been elucidated1-4, but the molecular details of how the other G-protein classes couple to GPCRs are unknown. Here we present the cryo-electron microscopy structure of the serotonin 5-HT1B receptor (5-HT1BR) bound to the agonist donitriptan and coupled to an engineered Go heterotrimer. In this complex, 5-HT1BR is in an active state; the intracellular domain of the receptor is in a similar conformation to that observed for the β2-adrenoceptor (β2AR) 3 or the adenosine A2A receptor (A2AR) 1 in complex with Gs. In contrast to the complexes with Gs, the gap between the receptor and the Gβ-subunit in the Go-5-HT1BR complex precludes molecular contacts, and the interface between the Gα-subunit of Go and the receptor is considerably smaller. These differences are likely to be caused by the differences in the interactions with the C terminus of the Go α-subunit. The molecular variations between the interfaces of Go and Gs in complex with GPCRs may contribute substantially to both the specificity of coupling and the kinetics of signalling.}, } @article {pmid29925950, year = {2018}, author = {Yu, R and Wang, X and Moazed, D}, title = {Epigenetic inheritance mediated by coupling of RNAi and histone H3K9 methylation.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {615-619}, doi = {10.1038/s41586-018-0239-3}, pmid = {29925950}, issn = {1476-4687}, support = {GM072805/NH/NIH HHS/United States ; R01 GM072805/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; //Howard Hughes Medical Institute/United States ; T32 GM096911/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Cell Cycle Proteins/genetics ; Epigenomics ; Feedback, Physiological ; Genes, Fungal/genetics ; Heterochromatin/genetics/metabolism ; Histones/*metabolism ; Lysine/*metabolism ; *Methylation ; Methyltransferases/genetics ; Nuclear Proteins/genetics ; *RNA Interference ; Schizosaccharomyces/cytology/*genetics/metabolism ; Schizosaccharomyces pombe Proteins/genetics ; }, abstract = {Histone post-translational modifications (PTMs) are associated with epigenetic states that form the basis for cell-type-specific gene expression1,2. Once established, histone PTMs can be maintained by positive feedback involving enzymes that recognize a pre-existing histone modification and catalyse the same modification on newly deposited histones. Recent studies suggest that in wild-type cells, histone PTM-based positive feedback is too weak to mediate epigenetic inheritance in the absence of other inputs3-7. RNA interference (RNAi)-mediated histone H3 lysine 9 methylation (H3K9me) and heterochromatin formation define a potential epigenetic inheritance mechanism in which positive feedback involving short interfering RNA (siRNA) amplification can be directly coupled to histone PTM positive feedback8-14. However, it is not known whether the coupling of these two feedback loops can maintain epigenetic silencing independently of DNA sequence and in the absence of enabling mutations that disrupt genome-wide chromatin structure or transcription15-17. Here, using the fission yeast Schizosaccharomyces pombe, we show that siRNA-induced H3K9me and silencing of a euchromatic gene can be epigenetically inherited in cis during multiple mitotic and meiotic cell divisions in wild-type cells. This inheritance involves the spreading of secondary siRNAs and H3K9me3 to the targeted gene and surrounding areas, and requires both RNAi and H3K9me, suggesting that the siRNA and H3K9me positive-feedback loops act synergistically to maintain silencing. By contrast, when maintained solely by histone PTM positive feedback, silencing is erased by H3K9 demethylation promoted by Epe1, or by interallelic interactions that occur after mating to cells containing an expressed allele even in the absence of Epe1. These findings demonstrate that the RNAi machinery can mediate transgenerational epigenetic inheritance independently of DNA sequence or enabling mutations, and reveal a role for the coupling of the siRNA and H3K9me positive-feedback loops in the protection of epigenetic alleles from erasure.}, } @article {pmid29925949, year = {2018}, author = {Pushkarev, A and Inoue, K and Larom, S and Flores-Uribe, J and Singh, M and Konno, M and Tomida, S and Ito, S and Nakamura, R and Tsunoda, SP and Philosof, A and Sharon, I and Yutin, N and Koonin, EV and Kandori, H and Béjà, O}, title = {A distinct abundant group of microbial rhodopsins discovered using functional metagenomics.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {595-599}, doi = {10.1038/s41586-018-0225-9}, pmid = {29925949}, issn = {1476-4687}, mesh = {Amino Acid Sequence ; Eukaryota/chemistry ; Evolution, Molecular ; *Metagenomics ; Rhodopsin/*analysis/chemistry/*classification/radiation effects ; Rhodopsins, Microbial/analysis/chemistry/classification/radiation effects ; }, abstract = {Many organisms capture or sense sunlight using rhodopsin pigments1,2, which are integral membrane proteins that bind retinal chromophores. Rhodopsins comprise two distinct protein families 1 , type-1 (microbial rhodopsins) and type-2 (animal rhodopsins). The two families share similar topologies and contain seven transmembrane helices that form a pocket in which retinal is linked covalently as a protonated Schiff base to a lysine at the seventh transmembrane helix2,3. Type-1 and type-2 rhodopsins show little or no sequence similarity to each other, as a consequence of extensive divergence from a common ancestor or convergent evolution of similar structures 1 . Here we report a previously unknown and diverse family of rhodopsins-which we term the heliorhodopsins-that we identified using functional metagenomics and that are distantly related to type-1 rhodopsins. Heliorhodopsins are embedded in the membrane with their N termini facing the cell cytoplasm, an orientation that is opposite to that of type-1 or type-2 rhodopsins. Heliorhodopsins show photocycles that are longer than one second, which is suggestive of light-sensory activity. Heliorhodopsin photocycles accompany retinal isomerization and proton transfer, as in type-1 and type-2 rhodopsins, but protons are never released from the protein, even transiently. Heliorhodopsins are abundant and distributed globally; we detected them in Archaea, Bacteria, Eukarya and their viruses. Our findings reveal a previously unknown family of light-sensing rhodopsins that are widespread in the microbial world.}, } @article {pmid29925948, year = {2018}, author = {Danai, LV and Babic, A and Rosenthal, MH and Dennstedt, EA and Muir, A and Lien, EC and Mayers, JR and Tai, K and Lau, AN and Jones-Sali, P and Prado, CM and Petersen, GM and Takahashi, N and Sugimoto, M and Yeh, JJ and Lopez, N and Bardeesy, N and Fernandez-Del Castillo, C and Liss, AS and Koong, AC and Bui, J and Yuan, C and Welch, MW and Brais, LK and Kulke, MH and Dennis, C and Clish, CB and Wolpin, BM and Vander Heiden, MG}, title = {Altered exocrine function can drive adipose wasting in early pancreatic cancer.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {600-604}, pmid = {29925948}, issn = {1476-4687}, support = {U01 CA210171/CA/NCI NIH HHS/United States ; F32 CA213810/CA/NCI NIH HHS/United States ; R01 CA168653/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P01 CA117969/CA/NCI NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; P50 CA102701/CA/NCI NIH HHS/United States ; F32 CA210421/CA/NCI NIH HHS/United States ; P50 CA127003/CA/NCI NIH HHS/United States ; }, mesh = {Adipose Tissue/*metabolism/*pathology ; Animals ; Body Composition ; Disease Models, Animal ; Disease Progression ; Exocrine Pancreatic Insufficiency/*etiology/*metabolism/pathology ; Female ; Male ; Mice ; Pancreatic Neoplasms/*complications/metabolism/*pathology ; }, abstract = {Malignancy is accompanied by changes in the metabolism of both cells and the organism1,2. Pancreatic ductal adenocarcinoma (PDAC) is associated with wasting of peripheral tissues, a metabolic syndrome that lowers quality of life and has been proposed to decrease survival of patients with cancer3,4. Tissue wasting is a multifactorial disease and targeting specific circulating factors to reverse this syndrome has been mostly ineffective in the clinic5,6. Here we show that loss of both adipose and muscle tissue occurs early in the development of pancreatic cancer. Using mouse models of PDAC, we show that tumour growth in the pancreas but not in other sites leads to adipose tissue wasting, suggesting that tumour growth within the pancreatic environment contributes to this wasting phenotype. We find that decreased exocrine pancreatic function is a driver of adipose tissue loss and that replacement of pancreatic enzymes attenuates PDAC-associated wasting of peripheral tissues. Paradoxically, reversal of adipose tissue loss impairs survival in mice with PDAC. When analysing patients with PDAC, we find that depletion of adipose and skeletal muscle tissues at the time of diagnosis is common, but is not associated with worse survival. Taken together, these results provide an explanation for wasting of adipose tissue in early PDAC and suggest that early loss of peripheral tissue associated with pancreatic cancer may not impair survival.}, } @article {pmid29925947, year = {2018}, author = {Schrank, BR and Aparicio, T and Li, Y and Chang, W and Chait, BT and Gundersen, GG and Gottesman, ME and Gautier, J}, title = {Nuclear ARP2/3 drives DNA break clustering for homology-directed repair.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {61-66}, pmid = {29925947}, issn = {1476-4687}, support = {R01 GM037219/GM/NIGMS NIH HHS/United States ; F30 CA217049/CA/NCI NIH HHS/United States ; P41 GM103314/GM/NIGMS NIH HHS/United States ; S10 RR025686/RR/NCRR NIH HHS/United States ; P01 CA174653/CA/NCI NIH HHS/United States ; R35 CA197606/CA/NCI NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; P41 GM109824/GM/NIGMS NIH HHS/United States ; R01 GM099481/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/metabolism ; Actin-Related Protein 2-3 Complex/antagonists & inhibitors/*metabolism ; Actins/metabolism ; Animals ; Cell Extracts ; Cell Nucleus/*metabolism ; Chromatin/metabolism ; *DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; Female ; Movement ; Protein Binding ; Protein Transport ; *Recombinational DNA Repair ; Wiskott-Aldrich Syndrome Protein/metabolism ; Xenopus laevis/*genetics ; }, abstract = {DNA double-strand breaks repaired by non-homologous end joining display limited DNA end-processing and chromosomal mobility. By contrast, double-strand breaks undergoing homology-directed repair exhibit extensive processing and enhanced motion. The molecular basis of this movement is unknown. Here, using Xenopus laevis cell-free extracts and mammalian cells, we establish that nuclear actin, WASP, and the actin-nucleating ARP2/3 complex are recruited to damaged chromatin undergoing homology-directed repair. We demonstrate that nuclear actin polymerization is required for the migration of a subset of double-strand breaks into discrete sub-nuclear clusters. Actin-driven movements specifically affect double-strand breaks repaired by homology-directed repair in G2 cell cycle phase; inhibition of actin nucleation impairs DNA end-processing and homology-directed repair. By contrast, ARP2/3 is not enriched at double-strand breaks repaired by non-homologous end joining and does not regulate non-homologous end joining. Our findings establish that nuclear actin-based mobility shapes chromatin organization by generating repair domains that are essential for homology-directed repair in eukaryotic cells.}, } @article {pmid29925946, year = {2018}, author = {Caridi, CP and D'Agostino, C and Ryu, T and Zapotoczny, G and Delabaere, L and Li, X and Khodaverdian, VY and Amaral, N and Lin, E and Rau, AR and Chiolo, I}, title = {Nuclear F-actin and myosins drive relocalization of heterochromatic breaks.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {54-60}, pmid = {29925946}, issn = {1476-4687}, support = {P40 OD010949/OD/NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; R01 GM117376/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/*metabolism ; Actin-Related Protein 2-3 Complex/metabolism ; Animals ; Cell Line ; Cell Nucleus/*genetics/*metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; *DNA Breaks, Double-Stranded ; Drosophila Proteins/metabolism ; Drosophila melanogaster ; Heterochromatin/genetics/*metabolism ; Intracellular Signaling Peptides and Proteins/metabolism ; Mice ; *Movement ; Myosins/*metabolism ; Recombinational DNA Repair ; }, abstract = {Heterochromatin mainly comprises repeated DNA sequences that are prone to ectopic recombination. In Drosophila cells, 'safe' repair of heterochromatic double-strand breaks by homologous recombination relies on the relocalization of repair sites to the nuclear periphery before strand invasion. The mechanisms responsible for this movement were unknown. Here we show that relocalization occurs by directed motion along nuclear actin filaments assembled at repair sites by the Arp2/3 complex. Relocalization requires nuclear myosins associated with the heterochromatin repair complex Smc5/6 and the myosin activator Unc45, which is recruited to repair sites by Smc5/6. ARP2/3, actin nucleation and myosins also relocalize heterochromatic double-strand breaks in mouse cells. Defects in this pathway result in impaired heterochromatin repair and chromosome rearrangements. These findings identify de novo nuclear actin filaments and myosins as effectors of chromatin dynamics for heterochromatin repair and stability in multicellular eukaryotes.}, } @article {pmid29925945, year = {2018}, author = {Draper-Joyce, CJ and Khoshouei, M and Thal, DM and Liang, YL and Nguyen, ATN and Furness, SGB and Venugopal, H and Baltos, JA and Plitzko, JM and Danev, R and Baumeister, W and May, LT and Wootten, D and Sexton, PM and Glukhova, A and Christopoulos, A}, title = {Structure of the adenosine-bound human adenosine A1 receptor-Gi complex.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {559-563}, doi = {10.1038/s41586-018-0236-6}, pmid = {29925945}, issn = {1476-4687}, mesh = {Adenosine/*chemistry/*metabolism ; Binding Sites ; *Cryoelectron Microscopy ; GTP-Binding Protein alpha Subunits, Gi-Go/*chemistry/metabolism/*ultrastructure ; GTP-Binding Protein alpha Subunits, Gs/chemistry/metabolism ; Humans ; Models, Molecular ; Receptor, Adenosine A1/*chemistry/metabolism/*ultrastructure ; Rotation ; Substrate Specificity ; }, abstract = {The class A adenosine A1 receptor (A1R) is a G-protein-coupled receptor that preferentially couples to inhibitory Gi/o heterotrimeric G proteins, has been implicated in numerous diseases, yet remains poorly targeted. Here we report the 3.6 Å structure of the human A1R in complex with adenosine and heterotrimeric Gi2 protein determined by Volta phase plate cryo-electron microscopy. Compared to inactive A1R, there is contraction at the extracellular surface in the orthosteric binding site mediated via movement of transmembrane domains 1 and 2. At the intracellular surface, the G protein engages the A1R primarily via amino acids in the C terminus of the Gαi α5-helix, concomitant with a 10.5 Å outward movement of the A1R transmembrane domain 6. Comparison with the agonist-bound β2 adrenergic receptor-Gs-protein complex reveals distinct orientations for each G-protein subtype upon engagement with its receptor. This active A1R structure provides molecular insights into receptor and G-protein selectivity.}, } @article {pmid29925944, year = {2018}, author = {Schwalie, PC and Dong, H and Zachara, M and Russeil, J and Alpern, D and Akchiche, N and Caprara, C and Sun, W and Schlaudraff, KU and Soldati, G and Wolfrum, C and Deplancke, B}, title = {A stromal cell population that inhibits adipogenesis in mammalian fat depots.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {103-108}, doi = {10.1038/s41586-018-0226-8}, pmid = {29925944}, issn = {1476-4687}, mesh = {Adipocytes/cytology/metabolism ; *Adipogenesis ; Animals ; Diabetes Mellitus, Type 2/metabolism ; Female ; Gene Expression Profiling ; Humans ; Insulin Resistance ; Male ; Mice ; Paracrine Communication ; Single-Cell Analysis ; Stem Cells/cytology/metabolism ; Stromal Cells/*cytology/metabolism ; Subcutaneous Fat/*cytology/metabolism ; Thromboplastin/metabolism ; }, abstract = {Adipocyte development and differentiation have an important role in the aetiology of obesity and its co-morbidities1,2. Although multiple studies have investigated the adipogenic stem and precursor cells that give rise to mature adipocytes3-14, our understanding of their in vivo origin and properties is incomplete2,15,16. This is partially due to the highly heterogeneous and unstructured nature of adipose tissue depots17, which has proven difficult to molecularly dissect using classical approaches such as fluorescence-activated cell sorting and Cre-lox lines based on candidate marker genes16,18. Here, using the resolving power of single-cell transcriptomics19 in a mouse model, we reveal distinct subpopulations of adipose stem and precursor cells in the stromal vascular fraction of subcutaneous adipose tissue. We identify one of these subpopulations as CD142+ adipogenesis-regulatory cells, which can suppress adipocyte formation in vivo and in vitro in a paracrine manner. We show that adipogenesis-regulatory cells are refractory to adipogenesis and that they are functionally conserved in humans. Our findings point to a potentially critical role for adipogenesis-regulatory cells in modulating adipose tissue plasticity, which is linked to metabolic control, differential insulin sensitivity and type 2 diabetes.}, } @article {pmid29925943, year = {2018}, author = {Liang, Y and Zhang, X and MacMillan, DWC}, title = {Decarboxylative sp3 C-N coupling via dual copper and photoredox catalysis.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {83-88}, pmid = {29925943}, issn = {1476-4687}, support = {R01 GM103558/GM/NIGMS NIH HHS/United States ; }, mesh = {Amides/chemistry ; Amines/chemistry ; Aniline Compounds/chemistry ; Carbon/*chemistry ; Carboxylic Acids/chemistry ; Catalysis ; Copper/*chemistry ; *Decarboxylation ; Nitrogen/*chemistry ; Pharmaceutical Preparations/chemistry ; *Photochemical Processes ; Sulfonamides/chemistry ; }, abstract = {Over the past three decades, considerable progress has been made in the development of methods to construct sp2 carbon-nitrogen (C-N) bonds using palladium, copper or nickel catalysis1,2. However, the incorporation of alkyl substrates to form sp3 C-N bonds remains one of the major challenges in the field of cross-coupling chemistry. Here we demonstrate that the synergistic combination of copper catalysis and photoredox catalysis can provide a general platform from which to address this challenge. This cross-coupling system uses naturally abundant alkyl carboxylic acids and commercially available nitrogen nucleophiles as coupling partners. It is applicable to a wide variety of primary, secondary and tertiary alkyl carboxylic acids (through iodonium activation), as well as a vast array of nitrogen nucleophiles: nitrogen heterocycles, amides, sulfonamides and anilines can undergo C-N coupling to provide N-alkyl products in good to excellent efficiency, at room temperature and on short timescales (five minutes to one hour). We demonstrate that this C-N coupling protocol proceeds with high regioselectivity using substrates that contain several amine groups, and can also be applied to complex drug molecules, enabling the rapid construction of molecular complexity and the late-stage functionalization of bioactive pharmaceuticals.}, } @article {pmid29925942, year = {2018}, author = {Ma, K and Gong, Y and Aubert, T and Turker, MZ and Kao, T and Doerschuk, PC and Wiesner, U}, title = {Self-assembly of highly symmetrical, ultrasmall inorganic cages directed by surfactant micelles.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {577-580}, doi = {10.1038/s41586-018-0221-0}, pmid = {29925942}, issn = {1476-4687}, support = {U54 CA199081/CA/NCI NIH HHS/United States ; }, mesh = {Cryoelectron Microscopy ; *Micelles ; Microscopy, Electron, Transmission ; Silicon Dioxide/*chemical synthesis/*chemistry ; Surface-Active Agents/*chemistry ; }, abstract = {Nanometre-sized objects with highly symmetrical, cage-like polyhedral shapes, often with icosahedral symmetry, have recently been assembled from DNA1-3, RNA 4 or proteins5,6 for applications in biology and medicine. These achievements relied on advances in the development of programmable self-assembling biological materials7-10, and on rapidly developing techniques for generating three-dimensional (3D) reconstructions from cryo-electron microscopy images of single particles, which provide high-resolution structural characterization of biological complexes11-13. Such single-particle 3D reconstruction approaches have not yet been successfully applied to the identification of synthetic inorganic nanomaterials with highly symmetrical cage-like shapes. Here, however, using a combination of cryo-electron microscopy and single-particle 3D reconstruction, we suggest the existence of isolated ultrasmall (less than 10 nm) silica cages ('silicages') with dodecahedral structure. We propose that such highly symmetrical, self-assembled cages form through the arrangement of primary silica clusters in aqueous solutions on the surface of oppositely charged surfactant micelles. This discovery paves the way for nanoscale cages made from silica and other inorganic materials to be used as building blocks for a wide range of advanced functional-materials applications.}, } @article {pmid29925941, year = {2018}, author = {, }, title = {Author Correction: Comprehensive molecular profiling of lung adenocarcinoma.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {E12}, doi = {10.1038/s41586-018-0228-6}, pmid = {29925941}, issn = {1476-4687}, abstract = {In Supplementary Table 7 of this Article, the iCLUSTER output column contained incorrected cluster labels. This table has been corrected online. Corrected online 08 October 2014 - The surname of author Kristen Rodgers was misspelled 'Rogers'. This has been corrected online.}, } @article {pmid29925940, year = {2018}, author = {Andersen, TG and Naseer, S and Ursache, R and Wybouw, B and Smet, W and De Rybel, B and Vermeer, JEM and Geldner, N}, title = {Author Correction: Diffusible repression of cytokinin signalling produces endodermal symmetry and passage cells.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {E9}, doi = {10.1038/s41586-018-0231-y}, pmid = {29925940}, issn = {1476-4687}, abstract = {In this Letter, owing to a copying error in Illustrator, the two centre panels in Extended Data Fig. 7a were identical. This error has been corrected online. The old, incorrect Extended Data Fig. 7 is shown in the Supplementary Information to this Amendment for transparency. Some typos ('occurence') in Figs. 1, 2 and 3 have also been corrected and the publication details for ref. 32 have been added.}, } @article {pmid29925939, year = {2018}, author = {Vanlandewijck, M and He, L and Mäe, MA and Andrae, J and Ando, K and Del Gaudio, F and Nahar, K and Lebouvier, T and Laviña, B and Gouveia, L and Sun, Y and Raschperger, E and Räsänen, M and Zarb, Y and Mochizuki, N and Keller, A and Lendahl, U and Betsholtz, C}, title = {Author Correction: A molecular atlas of cell types and zonation in the brain vasculature.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {E3}, doi = {10.1038/s41586-018-0232-x}, pmid = {29925939}, issn = {1476-4687}, abstract = {In Fig. 1b of this Article, 'Csf1r' was misspelt 'Csfr1'. In addition, in Extended Data Fig. 11b, owing to an error during figure formatting, the genes listed in the first column shifted down three rows below the first gene on the list, causing a mismatch between the gene names and their characteristics. These errors have been corrected online, and the original Extended Data Fig. 11b is provided as Supplementary Information to the accompanying Amendment.}, } @article {pmid29925605, year = {2018}, author = {Santolini, M and Barabási, AL}, title = {Predicting perturbation patterns from the topology of biological networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6375-E6383}, pmid = {29925605}, issn = {1091-6490}, support = {P01 HL132825/HL/NHLBI NIH HHS/United States ; P50 HG004233/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacteria/genetics/*metabolism ; Chemotaxis/*physiology ; Gene Expression Regulation, Bacterial/*physiology ; *Models, Biological ; }, abstract = {High-throughput technologies, offering an unprecedented wealth of quantitative data underlying the makeup of living systems, are changing biology. Notably, the systematic mapping of the relationships between biochemical entities has fueled the rapid development of network biology, offering a suitable framework to describe disease phenotypes and predict potential drug targets. However, our ability to develop accurate dynamical models remains limited, due in part to the limited knowledge of the kinetic parameters underlying these interactions. Here, we explore the degree to which we can make reasonably accurate predictions in the absence of the kinetic parameters. We find that simple dynamically agnostic models are sufficient to recover the strength and sign of the biochemical perturbation patterns observed in 87 biological models for which the underlying kinetics are known. Surprisingly, a simple distance-based model achieves 65% accuracy. We show that this predictive power is robust to topological and kinetic parameter perturbations, and we identify key network properties that can increase up to 80% the recovery rate of the true perturbation patterns. We validate our approach using experimental data on the chemotactic pathway in bacteria, finding that a network model of perturbation spreading predicts with ∼80% accuracy the directionality of gene expression and phenotype changes in knock-out and overproduction experiments. These findings show that the steady advances in mapping out the topology of biochemical interaction networks opens avenues for accurate perturbation spread modeling, with direct implications for medicine and drug development.}, } @article {pmid29925604, year = {2018}, author = {Malvezzi, M and Andra, KK and Pandey, K and Lee, BC and Falzone, ME and Brown, A and Iqbal, R and Menon, AK and Accardi, A}, title = {Out-of-the-groove transport of lipids by TMEM16 and GPCR scramblases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {E7033-E7042}, pmid = {29925604}, issn = {1091-6490}, support = {P41 GM103310/GM/NIGMS NIH HHS/United States ; R21 EY028314/EY/NEI NIH HHS/United States ; T32 GM008539/GM/NIGMS NIH HHS/United States ; R01 GM106717/GM/NIGMS NIH HHS/United States ; S10 OD019994/OD/NIH HHS/United States ; }, mesh = {Anoctamins/genetics/*metabolism ; Biological Transport, Active/physiology ; HEK293 Cells ; Humans ; Lipid Metabolism/*physiology ; Phospholipid Transfer Proteins/genetics/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Saccharomyces cerevisiae ; }, abstract = {Phospholipid scramblases externalize phosphatidylserine to facilitate numerous physiological processes. Several members of the structurally unrelated TMEM16 and G protein-coupled receptor (GPCR) protein families mediate phospholipid scrambling. The structure of a TMEM16 scramblase shows a membrane-exposed hydrophilic cavity, suggesting that scrambling occurs via the ‟credit-card" mechanism where lipid headgroups permeate through the cavity while their tails remain associated with the membrane core. Here we show that afTMEM16 and opsin, representatives of the TMEM16 and GCPR scramblase families, transport phospholipids with polyethylene glycol headgroups whose globular dimensions are much larger than the width of the cavity. This suggests that transport of these large headgroups occurs outside rather than within the cavity. These large lipids are scrambled at rates comparable to those of normal phospholipids and their presence in the reconstituted vesicles promotes scrambling of normal phospholipids. This suggests that both large and small phospholipids can move outside the cavity. We propose that the conformational rearrangements underlying TMEM16- and GPCR-mediated credit-card scrambling locally deform the membrane to allow transbilayer lipid translocation outside the cavity and that both mechanisms underlie transport of normal phospholipids.}, } @article {pmid29925603, year = {2018}, author = {Gekelman, W and Tang, SW and DeHaas, T and Vincena, S and Pribyl, P and Sydora, R}, title = {Spiky electric and magnetic field structures in flux rope experiments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1721343115}, pmid = {29925603}, issn = {1091-6490}, abstract = {Magnetic flux ropes are structures that are common in the corona of the sun and presumably all stars. They can be thought of as the building blocks of solar structures. They have been observed in Earth's magnetotail and near Mars and Venus. When multiple flux ropes are present magnetic field line reconnection, which converts magnetic energy to other forms, can occur when they collide. The structure of multiple magnetic ropes, the interactions between multiple ropes, and their topological properties such as helicity and writhing have been studied theoretically and in laboratory experiments. Here, we report on spiky potential and magnetic fields associated with the ropes. We show that the potential structures are chaotic for a range of their temporal half-widths and the probability density function (PDF) of their widths resembles the statistical distribution of crumpled paper. The spatial structure of the magnetic spikes is revealed using a correlation counting method. Computer simulation suggests that the potential structures are the nonlinear end result of an instability involving relative drift between ions and electrons.}, } @article {pmid29925602, year = {2018}, author = {Coalson, TS and Van Essen, DC and Glasser, MF}, title = {The impact of traditional neuroimaging methods on the spatial localization of cortical areas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6356-E6365}, pmid = {29925602}, issn = {1091-6490}, support = {F30 MH097312/MH/NIMH NIH HHS/United States ; R01 MH060974/MH/NIMH NIH HHS/United States ; R24 MH108315/MH/NIMH NIH HHS/United States ; U54 MH091657/MH/NIMH NIH HHS/United States ; }, mesh = {Cerebral Cortex/*diagnostic imaging/*physiology ; Connectome/*methods ; Humans ; }, abstract = {Localizing human brain functions is a long-standing goal in systems neuroscience. Toward this goal, neuroimaging studies have traditionally used volume-based smoothing, registered data to volume-based standard spaces, and reported results relative to volume-based parcellations. A novel 360-area surface-based cortical parcellation was recently generated using multimodal data from the Human Connectome Project, and a volume-based version of this parcellation has frequently been requested for use with traditional volume-based analyses. However, given the major methodological differences between traditional volumetric and Human Connectome Project-style processing, the utility and interpretability of such an altered parcellation must first be established. By starting from automatically generated individual-subject parcellations and processing them with different methodological approaches, we show that traditional processing steps, especially volume-based smoothing and registration, substantially degrade cortical area localization compared with surface-based approaches. We also show that surface-based registration using features closely tied to cortical areas, rather than to folding patterns alone, improves the alignment of areas, and that the benefits of high-resolution acquisitions are largely unexploited by traditional volume-based methods. Quantitatively, we show that the most common version of the traditional approach has spatial localization that is only 35% as good as the best surface-based method as assessed using two objective measures (peak areal probabilities and "captured area fraction" for maximum probability maps). Finally, we demonstrate that substantial challenges exist when attempting to accurately represent volume-based group analysis results on the surface, which has important implications for the interpretability of studies, both past and future, that use these volume-based methods.}, } @article {pmid29925601, year = {2018}, author = {Molnár, G and Rodney, D and Martoïa, F and Dumont, PJJ and Nishiyama, Y and Mazeau, K and Orgéas, L}, title = {Cellulose crystals plastify by localized shear.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7260-7265}, pmid = {29925601}, issn = {1091-6490}, abstract = {Cellulose microfibrils are the principal structural building blocks of wood and plants. Their crystalline domains provide outstanding mechanical properties. Cellulose microfibrils have thus a remarkable potential as eco-friendly fibrous reinforcements for structural engineered materials. However, the elastoplastic properties of cellulose crystals remain poorly understood. Here, we use atomistic simulations to determine the plastic shear resistance of cellulose crystals and analyze the underpinning atomic deformation mechanisms. In particular, we demonstrate how the complex and adaptable atomic structure of crystalline cellulose controls its anisotropic elastoplastic behavior. For perfect crystals, we show that shear occurs through localized bands along with noticeable dilatancy. Depending on the shear direction, not only noncovalent interactions between cellulose chains but also local deformations, translations, and rotations of the cellulose macromolecules contribute to the response of the crystal. We also reveal the marked effect of crystalline defects like dislocations, which decrease both the yield strength and the dilatancy, in a way analogous to that of metallic crystals.}, } @article {pmid29925600, year = {2018}, author = {Pedersen, MC and Hyde, ST}, title = {Polyhedra and packings from hyperbolic honeycombs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6905-6910}, pmid = {29925600}, issn = {1091-6490}, abstract = {We derive more than 80 embeddings of 2D hyperbolic honeycombs in Euclidean 3 space, forming 3-periodic infinite polyhedra with cubic symmetry. All embeddings are "minimally frustrated," formed by removing just enough isometries of the (regular, but unphysical) 2D hyperbolic honeycombs [Formula: see text], [Formula: see text], [Formula: see text], [Formula: see text], and [Formula: see text] to allow embeddings in Euclidean 3 space. Nearly all of these triangulated "simplicial polyhedra" have symmetrically identical vertices, and most are chiral. The most symmetric examples include 10 infinite "deltahedra," with equilateral triangular faces, 6 of which were previously unknown and some of which can be described as packings of Platonic deltahedra. We describe also related cubic crystalline packings of equal hyperbolic discs in 3 space that are frustrated analogues of optimally dense hyperbolic disc packings. The 10-coordinated packings are the least "loosened" Euclidean embeddings, although frustration swells all of the hyperbolic disc packings to give less dense arrays than the flat penny-packing even though their unfrustrated analogues in [Formula: see text] are denser.}, } @article {pmid29925599, year = {2018}, author = {Van Duyne, R and Freed, EO}, title = {HIV-1 packs in PACSIN2 for cell-to-cell spread.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6885-6887}, pmid = {29925599}, issn = {1091-6490}, mesh = {*Adaptor Proteins, Signal Transducing ; *HIV-1 ; Signal Transduction ; }, } @article {pmid29925598, year = {2018}, author = {Cherlin, AJ}, title = {Psychological health and socioeconomic status among non-Hispanic whites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7176-7178}, pmid = {29925598}, issn = {1091-6490}, mesh = {*European Continental Ancestry Group ; Hispanic Americans ; Humans ; *Social Class ; Socioeconomic Factors ; United States ; }, } @article {pmid29925597, year = {2018}, author = {Westmeier, D and Solouk-Saran, D and Vallet, C and Siemer, S and Docter, D and Götz, H and Männ, L and Hasenberg, A and Hahlbrock, A and Erler, K and Reinhardt, C and Schilling, O and Becker, S and Gunzer, M and Hasenberg, M and Knauer, SK and Stauber, RH}, title = {Nanoparticle decoration impacts airborne fungal pathobiology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7087-7092}, pmid = {29925597}, issn = {1091-6490}, mesh = {A549 Cells ; Animals ; Aspergillus fumigatus/*immunology ; Cytokines/*immunology ; Humans ; Lung/*immunology/pathology ; Mice ; *Nanoparticles ; Protein Corona/immunology ; Pulmonary Aspergillosis/*immunology/pathology ; Spores, Fungal/*immunology ; THP-1 Cells ; }, abstract = {Airborne fungal pathogens, predominantly Aspergillus fumigatus, can cause severe respiratory tract diseases. Here we show that in environments, fungal spores can already be decorated with nanoparticles. Using representative controlled nanoparticle models, we demonstrate that various nanoparticles, but not microparticles, rapidly and stably associate with spores, without specific functionalization. Nanoparticle-spore complex formation was enhanced by small nanoparticle size rather than by material, charge, or "stealth" modifications and was concentration-dependently reduced by the formation of environmental or physiological biomolecule coronas. Assembly of nanoparticle-spore surface hybrid structures affected their pathobiology, including reduced sensitivity against defensins, uptake into phagocytes, lung cell toxicity, and TLR/cytokine-mediated inflammatory responses. Following infection of mice, nanoparticle-spore complexes were detectable in the lung and less efficiently eliminated by the pulmonary immune defense, thereby enhancing A. fumigatus infections in immunocompromised animals. Collectively, self-assembly of nanoparticle-fungal complexes affects their (patho)biological identity, which may impact human health and ecology.}, } @article {pmid29925596, year = {2018}, author = {Hawkins, JA and Jones, SK and Finkelstein, IJ and Press, WH}, title = {Indel-correcting DNA barcodes for high-throughput sequencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6217-E6226}, pmid = {29925596}, issn = {1091-6490}, support = {F32 AG053051/AG/NIA NIH HHS/United States ; R01 GM120554/GM/NIGMS NIH HHS/United States ; R01 GM124141/GM/NIGMS NIH HHS/United States ; }, mesh = {*Base Sequence ; *DNA Barcoding, Taxonomic ; *High-Throughput Nucleotide Sequencing ; *INDEL Mutation ; }, abstract = {Many large-scale, high-throughput experiments use DNA barcodes, short DNA sequences prepended to DNA libraries, for identification of individuals in pooled biomolecule populations. However, DNA synthesis and sequencing errors confound the correct interpretation of observed barcodes and can lead to significant data loss or spurious results. Widely used error-correcting codes borrowed from computer science (e.g., Hamming, Levenshtein codes) do not properly account for insertions and deletions (indels) in DNA barcodes, even though deletions are the most common type of synthesis error. Here, we present and experimentally validate filled/truncated right end edit (FREE) barcodes, which correct substitution, insertion, and deletion errors, even when these errors alter the barcode length. FREE barcodes are designed with experimental considerations in mind, including balanced guanine-cytosine (GC) content, minimal homopolymer runs, and reduced internal hairpin propensity. We generate and include lists of barcodes with different lengths and error correction levels that may be useful in diverse high-throughput applications, including >106 single-error-correcting 16-mers that strike a balance between decoding accuracy, barcode length, and library size. Moreover, concatenating two or more FREE codes into a single barcode increases the available barcode space combinatorially, generating lists with >1015 error-correcting barcodes. The included software for creating barcode libraries and decoding sequenced barcodes is efficient and designed to be user-friendly for the general biology community.}, } @article {pmid29925595, year = {2018}, author = {Li, C and Wu, Z and Xu, H}, title = {Maximum principles and Bôcher type theorems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6976-6979}, doi = {10.1073/pnas.1804225115}, pmid = {29925595}, issn = {1091-6490}, abstract = {We establish maximum principles and Bôcher-type theorems for superharmonic and fractional superharmonic nonnegative functions on a punctured ball. Connecting maximum principles with Bôcher-type theorems is a crucial observation.}, } @article {pmid29925594, year = {2018}, author = {Dong, G and Fan, J and Shekhtman, LM and Shai, S and Du, R and Tian, L and Chen, X and Stanley, HE and Havlin, S}, title = {Resilience of networks with community structure behaves as if under an external field.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6911-6915}, pmid = {29925594}, issn = {1091-6490}, abstract = {Although detecting and characterizing community structure is key in the study of networked systems, we still do not understand how community structure affects systemic resilience and stability. We use percolation theory to develop a framework for studying the resilience of networks with a community structure. We find both analytically and numerically that interlinks (the connections among communities) affect the percolation phase transition in a way similar to an external field in a ferromagnetic- paramagnetic spin system. We also study universality class by defining the analogous critical exponents δ and γ, and we find that their values in various models and in real-world coauthor networks follow the fundamental scaling relations found in physical phase transitions. The methodology and results presented here facilitate the study of network resilience and also provide a way to understand phase transitions under external fields.}, } @article {pmid29925435, year = {2018}, author = {Le Gallo, M and de la Motte Rouge, T and Poissonnier, A and Lavoué, V and Tas, P and Leveque, J and Godey, F and Legembre, P}, title = {Tumor analysis: freeze-thawing cycle of triple-negative breast cancer cells alters tumor CD24/CD44 profiles and the percentage of tumor-infiltrating immune cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {401}, pmid = {29925435}, issn = {1756-0500}, support = {PL BIo//INCA/ ; }, mesh = {*Biomarkers, Tumor ; *CD24 Antigen ; Cryopreservation/*standards ; Female ; Humans ; *Hyaluronan Receptors ; *Leukocyte Common Antigens ; Specimen Handling/*standards ; Triple Negative Breast Neoplasms/*diagnosis/immunology ; }, abstract = {OBJECTIVE: The use of novel methods to characterize living tumor cells relies on well-conceived biobanks. Herein, we raised the question of whether the composition of fresh and freeze/thawed dissociated tumor samples is comparable in terms of quantitative and qualitative profiling.

RESULTS: Breast cancer is a heterogeneous disease, encompassing luminal A and B, basal/triple-negative breast cancer (TNBC), and ERBB2-like tumors. We examined living cells dissociated from TNBC and found that a classical freeze/thaw protocol leads to a marked reduction in the number of CD45-CD44LowCD24Low tumor cells. This, in turn, changed the percentage of tumor cells with certain CD44/CD24 expression patterns and changed the percentage of tumor-infiltrating immune cells. These cryopreservation-driven alterations in cellular phenotype make it impossible to compare fresh and frozen samples from the same patient directly. Moreover, the freeze/thaw process changed the transcriptomic signatures of triple-negative cancer stem cells in such a manner that hierarchical clustering no longer ranked them according to expected inter-individual differences. Overall, this study suggests that all analyses of living tumor cells should be conducted only using freshly dissociated tumors if we are to generate a robust scoring system for prognostic/predictive markers.}, } @article {pmid29925429, year = {2018}, author = {Tschitschko, B and Erdmann, S and DeMaere, MZ and Roux, S and Panwar, P and Allen, MA and Williams, TJ and Brazendale, S and Hancock, AM and Eloe-Fadrosh, EA and Cavicchioli, R}, title = {Genomic variation and biogeography of Antarctic haloarchaea.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {113}, pmid = {29925429}, issn = {2049-2618}, mesh = {Antarctic Regions ; Archaeal Viruses/*genetics/isolation & purification ; Base Sequence ; Genetic Variation/genetics ; Genome, Archaeal/*genetics ; Genomic Islands/genetics ; Geography ; Halorubrum/classification/*genetics/isolation & purification ; Lakes/microbiology ; Metagenome/genetics ; Microbiota/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The genomes of halophilic archaea (haloarchaea) often comprise multiple replicons. Genomic variation in haloarchaea has been linked to viral infection pressure and, in the case of Antarctic communities, can be caused by intergenera gene exchange. To expand understanding of genome variation and biogeography of Antarctic haloarchaea, here we assessed genomic variation between two strains of Halorubrum lacusprofundi that were isolated from Antarctic hypersaline lakes from different regions (Vestfold Hills and Rauer Islands). To assess variation in haloarchaeal populations, including the presence of genomic islands, metagenomes from six hypersaline Antarctic lakes were characterised.

RESULTS: The sequence of the largest replicon of each Hrr. lacusprofundi strain (primary replicon) was highly conserved, while each of the strains' two smaller replicons (secondary replicons) were highly variable. Intergenera gene exchange was identified, including the sharing of a type I-B CRISPR system. Evaluation of infectivity of an Antarctic halovirus provided experimental evidence for the differential susceptibility of the strains, bolstering inferences that strain variation is important for modulating interactions with viruses. A relationship was found between genomic structuring and the location of variation within replicons and genomic islands, demonstrating that the way in which haloarchaea accommodate genomic variability relates to replicon structuring. Metagenome read and contig mapping and clustering and scaling analyses demonstrated biogeographical patterning of variation consistent with environment and distance effects. The metagenome data also demonstrated that specific haloarchaeal species dominated the hypersaline systems indicating they are endemic to Antarctica.

CONCLUSION: The study describes how genomic variation manifests in Antarctic-lake haloarchaeal communities and provides the basis for future assessments of Antarctic regional and global biogeography of haloarchaea.}, } @article {pmid29925425, year = {2018}, author = {Ralapanawa, U and Alawattegama, ATM and Gunrathne, M and Tennakoon, S and Kularatne, SAM and Jayalath, T}, title = {Value of peripheral blood count for dengue severity prediction.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {400}, pmid = {29925425}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Cell Count/*standards ; Dengue/*blood/*diagnosis ; Female ; Humans ; Male ; Middle Aged ; Predictive Value of Tests ; Retrospective Studies ; Severe Dengue/blood/diagnosis ; Sri Lanka ; Young Adult ; }, abstract = {OBJECTIVE: This retrospective study was conducted in 2017 with the objective of evaluating the value of acute phase peripheral blood parameters in predicting dengue haemorrhagic fever (DHF). Patients, who were admitted to Teaching Hospital Peradeniya between January and August 2017 due to dengue illness, were recruited into this study.

RESULTS: A total of 515 patients participated in the study. Among them, 333 were DHF patients while 182 patients were managed as DF. There was a significant difference in mean values of platelets and haemoglobin observed during acute phase in non-leakers compared to the patients who progressed to DHF, while no significant difference was observed for white blood cells, neutrophils, lymphocytes and haematocrit values. A significantly higher mean value was observed in white blood cells and hemoglobin in leakers compared to non-leakers during day 5. Mean day 5 platelet value was significantly lower among leakers compared to non-leakers but no significant difference between haematocrit, neutrophil and lymphocyte values were observed. ROC curve performed for acute phase platelet values and haemoglobin values to gain a predictive value for female and male DHF patients and cut off values with high sensitivity and specificity to predict DHF could be obtained for the platelet count.}, } @article {pmid29925423, year = {2018}, author = {Brooks, B and Olm, MR and Firek, BA and Baker, R and Geller-McGrath, D and Reimer, SR and Soenjoyo, KR and Yip, JS and Dahan, D and Thomas, BC and Morowitz, MJ and Banfield, JF}, title = {The developing premature infant gut microbiome is a major factor shaping the microbiome of neonatal intensive care unit rooms.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {112}, pmid = {29925423}, issn = {2049-2618}, support = {R01 AI092531/AI/NIAID NIH HHS/United States ; S10 OD018174/OD/NIH HHS/United States ; }, mesh = {Aerosols ; Bacteria/*classification/genetics/*isolation & purification ; Base Sequence ; Dust ; Feces/microbiology ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Humans ; Infant, Newborn ; Infant, Premature ; Infant, Very Low Birth Weight ; *Intensive Care Units, Neonatal ; Premature Birth ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {BACKGROUND: The neonatal intensive care unit (NICU) contains a unique cohort of patients with underdeveloped immune systems and nascent microbiome communities. Patients often spend several months in the same room, and it has been previously shown that the gut microbiomes of these infants often resemble the microbes found in the NICU. Little is known, however, about the identity, persistence, and absolute abundance of NICU room-associated bacteria over long stretches of time. Here, we couple droplet digital PCR (ddPCR), 16S rRNA gene surveys, and recently published metagenomics data from infant gut samples to infer the extent to which the NICU microbiome is shaped by its room occupants.

RESULTS: Over 2832 swabs, wipes, and air samples were collected from 16 private-style NICU rooms housing very low birth weight (< 1500 g), premature (< 31 weeks' gestation) infants. For each infant, room samples were collected daily, Monday through Friday, for 1 month. The first samples from the first infant and the last samples from the last infant were collected 383 days apart. Twenty-two NICU locations spanning room surfaces, hands, electronics, sink basins, and air were collected. Results point to an incredibly simple room community where 5-10 taxa, mostly skin-associated, account for over 50% of the amplicon reads. Biomass estimates reveal four to five orders of magnitude difference between the least to the most dense microbial communities, air, and sink basins, respectively. Biomass trends from bioaerosol samples and petri dish dust collectors suggest occupancy to be a main driver of suspended biological particles within the NICU. Using a machine learning algorithm to classify the origin of room samples, we show that each room has a unique microbial fingerprint. Several important taxa driving this model were dominant gut colonizers of infants housed within each room.

CONCLUSIONS: Despite regular cleaning of hospital surfaces, bacterial biomass was detectable at varying densities. A room-specific microbiome signature was detected, suggesting microbes seeding NICU surfaces are sourced from reservoirs within the room and that these reservoirs contain actively dividing cells. Collectively, the data suggests that hospitalized infants, in combination with their caregivers, shape the microbiome of NICU rooms.}, } @article {pmid29925417, year = {2018}, author = {Komagamine, J}, title = {The efficacy of high-dose penicillin G for pneumococcal pneumonia diagnosed based on initial comprehensive assessment at admission: an observational study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {399}, pmid = {29925417}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/administration & dosage/*pharmacology ; Female ; Humans ; Male ; Middle Aged ; *Outcome Assessment (Health Care) ; Patient Admission ; Penicillin G/administration & dosage/*pharmacology ; Pneumonia, Pneumococcal/diagnosis/*drug therapy/microbiology/urine ; Streptococcus pneumoniae/*immunology ; }, abstract = {OBJECTIVES: High-dose penicillin therapy is effective in approximately 90% of pneumococcal pneumonia cases diagnosed based on urinary pneumococcal antigen tests or Gram staining at admission. The efficacy of high-dose penicillin therapy for pneumococcal pneumonia diagnosed based on an initial comprehensive assessment comprising a syndromic approach, Gram staining of sputum and urinary pneumococcal antigen testing was investigated.

RESULTS: Seventy adult patients diagnosed with pneumococcal pneumonia based on an initial comprehensive assessment and treated with high-dose penicillin G at admission were included. The median patient age was 76.5 years, and 37.1% of the patients were women. The urinary pneumococcal antigen test was positive in 67.1% of all patients, and Gram staining of sputum showed that gram-positive cocci were dominant in 58.6% of the patients. The primary outcome was treatment success based on vital signs until day 6. Treatment with high-dose penicillin G was effective in 87.1% of the patients (95% CI 79.1-95.2%), and the proportion of patients who received other antibiotics because of treatment failure with penicillin G was only 5.7%. The efficacy of high-dose penicillin G treatment for pneumococcal pneumonia diagnosed based on a comprehensive assessment at admission may be comparable to that in previous reports.}, } @article {pmid29925415, year = {2018}, author = {Bouffaud, ML and Renoud, S and Dubost, A and Moënne-Loccoz, Y and Muller, D}, title = {1-Aminocyclopropane-1-carboxylate deaminase producers associated to maize and other Poaceae species.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {114}, pmid = {29925415}, issn = {2049-2618}, mesh = {*Bacteria/classification/enzymology/genetics ; Carbon-Carbon Lyases/*genetics/metabolism ; Deamination ; Microbiota/*genetics ; Plant Roots/*microbiology ; Rhizosphere ; *Soil Microbiology ; Zea mays/classification/*microbiology ; }, abstract = {BACKGROUND: Complex plant-microbe interactions have been established throughout evolutionary time, many of them with beneficial effects on the host in terms of plant growth, nutrition, or health. Some of the corresponding modes of action involve a modulation of plant hormonal balance, such as the deamination of the ethylene precursor 1-aminocyclopropane-1-carboxylate (ACC). Despite its ecological importance, our understanding of ACC deamination is impaired by a lack of direct molecular tools. Here, we developed PCR primers to quantify the ACC deaminase gene acdS and its mRNA in soil communities and assessed acdS+ microorganisms colonizing maize and other Poaceae species.

RESULTS: Effective acdS primers suitable for soil microbial communities were obtained, enabling recovery of bona fida acdS genes and transcripts of diverse genetic backgrounds. High numbers of acdS genes and transcripts were evidenced in the rhizosphere of Poaceae, and numbers fluctuated according to plant genotype. Illumina sequencing revealed taxonomic specificities of acdS+ microorganisms according to plant host. The phylogenetic distance between Poaceae genotypes correlated with acdS transcript numbers, but not with acdS gene numbers or the genetic distance between acdS functional groups.

CONCLUSION: The development of acdS primers enabled the first direct analysis of ACC deaminase functional group in soil and showed that plant ability to interact with soil-inhabiting acdS+ microorganisms could also involve particular plant traits unrelated to the evolutionary history of Poaceae species.}, } @article {pmid29925374, year = {2018}, author = {Codner, GF and Mianné, J and Caulder, A and Loeffler, J and Fell, R and King, R and Allan, AJ and Mackenzie, M and Pike, FJ and McCabe, CV and Christou, S and Joynson, S and Hutchison, M and Stewart, ME and Kumar, S and Simon, MM and Agius, L and Anstee, QM and Volynski, KE and Kullmann, DM and Wells, S and Teboul, L}, title = {Application of long single-stranded DNA donors in genome editing: generation and validation of mouse mutants.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {70}, pmid = {29925374}, issn = {1741-7007}, support = {UM1 HG006348/HG/NHGRI NIH HHS/United States ; U42 OD011174/OD/NIH HHS/United States ; 53658//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Recent advances in clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) genome editing have led to the use of long single-stranded DNA (lssDNA) molecules for generating conditional mutations. However, there is still limited available data on the efficiency and reliability of this method.

RESULTS: We generated conditional mouse alleles using lssDNA donor templates and performed extensive characterization of the resulting mutations. We observed that the use of lssDNA molecules as donors efficiently yielded founders bearing the conditional allele, with seven out of nine projects giving rise to modified alleles. However, rearranged alleles including nucleotide changes, indels, local rearrangements and additional integrations were also frequently generated by this method. Specifically, we found that alleles containing unexpected point mutations were found in three of the nine projects analyzed. Alleles originating from illegitimate repairs or partial integration of the donor were detected in eight projects. Furthermore, additional integrations of donor molecules were identified in four out of the seven projects analyzed by copy counting. This highlighted the requirement for a thorough allele validation by polymerase chain reaction, sequencing and copy counting of the mice generated through this method. We also demonstrated the feasibility of using lssDNA donors to generate thus far problematic point mutations distant from active CRISPR cutting sites by targeting two distinct genes (Gckr and Rims1). We propose a strategy to perform extensive quality control and validation of both types of mouse models generated using lssDNA donors.

CONCLUSION: lssDNA donors reproducibly generate conditional alleles and can be used to introduce point mutations away from CRISPR/Cas9 cutting sites in mice. However, our work demonstrates that thorough quality control of new models is essential prior to reliably experimenting with mice generated by this method. These advances in genome editing techniques shift the challenge of mutagenesis from generation to the validation of new mutant models.}, } @article {pmid29925370, year = {2018}, author = {Lanza, DG and Gaspero, A and Lorenzo, I and Liao, L and Zheng, P and Wang, Y and Deng, Y and Cheng, C and Zhang, C and Seavitt, JR and DeMayo, FJ and Xu, J and Dickinson, ME and Beaudet, AL and Heaney, JD}, title = {Comparative analysis of single-stranded DNA donors to generate conditional null mouse alleles.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {69}, pmid = {29925370}, issn = {1741-7007}, support = {P30 CA125123/CA/NCI NIH HHS/United States ; UM1 HG006348/HG/NHGRI NIH HHS/United States ; U42 OD011174/OD/NIH HHS/United States ; R01 CA182467/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: The International Mouse Phenotyping Consortium is generating null allele mice for every protein-coding gene in the genome and characterizing these mice to identify gene-phenotype associations. While CRISPR/Cas9-mediated null allele production in mice is highly efficient, generation of conditional alleles has proven to be more difficult. To test the feasibility of using CRISPR/Cas9 gene editing to generate conditional knockout mice for this large-scale resource, we employed Cas9-initiated homology-driven repair (HDR) with short and long single stranded oligodeoxynucleotides (ssODNs and lssDNAs).

RESULTS: Using pairs of single guide RNAs and short ssODNs to introduce loxP sites around a critical exon or exons, we obtained putative conditional allele founder mice, harboring both loxP sites, for 23 out of 30 targeted genes. LoxP sites integrated in cis in at least one mouse for 18 of 23 genes. However, loxP sites were mutagenized in 4 of the 18 in cis lines. HDR efficiency correlated with Cas9 cutting efficiency but was minimally influenced by ssODN homology arm symmetry. By contrast, using pairs of guides and single lssDNAs to introduce loxP-flanked exons, conditional allele founders were generated for all four genes targeted, although one founder was found to harbor undesired mutations within the lssDNA sequence interval. Importantly, when employing either ssODNs or lssDNAs, random integration events were detected.

CONCLUSIONS: Our studies demonstrate that Cas9-mediated HDR with pairs of ssODNs can generate conditional null alleles at many loci, but reveal inefficiencies when applied at scale. In contrast, lssDNAs are amenable to high-throughput production of conditional alleles when they can be employed. Regardless of the single-stranded donor utilized, it is essential to screen for sequence errors at sites of HDR and random insertion of donor sequences into the genome.}, } @article {pmid29925322, year = {2018}, author = {Jiang, J and Bai, J and Li, S and Li, X and Yang, L and He, Y}, title = {HTT2 promotes plant thermotolerance in Brassica rapa.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {127}, pmid = {29925322}, issn = {1471-2229}, support = {2016YFD0101900//National Programs for Science and Technology Development of China/ ; 31571261//National Natural Science Foundation of China/ ; }, mesh = {Arabidopsis ; Arabidopsis Proteins/*genetics/physiology ; *Genes, Plant ; Heat-Shock Response ; Hot Temperature ; Hypocotyl/growth & development ; Plant Proteins/*genetics/physiology ; Plants, Genetically Modified ; Real-Time Polymerase Chain Reaction ; Seedlings/genetics/physiology ; Thermotolerance/*genetics/physiology ; }, abstract = {BACKGROUND: Numerous regulatory genes participate in plant thermotolerance. In Arabidopsis, HEAT-INDUCED TAS1 TARGET2 (HTT2) is an important thermotolerance gene that is silenced by ta-siR255, a trans-acting siRNA. ta-siR255 is absent from heading Chinese cabbage (Brassica rapa ssp. pekinensis). Our previous attempt to overexpress the endogenous BrpHTT2 gene of heading Chinese cabbage (B. rapa ssp. pekinensis) failed because of cosuppression. In theory, heading Chinese cabbage can overexpress Arabidopsis HTT2 to improve thermotolerance in the absence of ta-siR255-mediated gene silencing and the weak potential of coexpression.

RESULTS: To test the potential application of HTT2 in improving crop thermotolerance, we transferred p35S::HTT2 to heading Chinese cabbage. We tested the leaf electrical conductivity, hypocotyl elongation, and survival percentage of p35S::HTT2 plants subjected to high-temperature (38 °C) and heat-shock (46 °C) treatment. The leaf electrical conductivity of p35S::HTT2 seedlings under high temperature decreased but did negligibly change under heat shock. The hypocotyl length of p35S::HTT2 seedlings increased under high temperature and heat shock. The survival rate of p35S::HTT2 seedlings increased under heat shock. BrpHsfs, a subset of heat-shock factor genes, were upregulated in p35S::HTT2 plants under high-temperature and heat shock conditions. In the field, transgenic plants with HTT2 appeared greener and formed leafy heads earlier than wild-type plants.

CONCLUSIONS: Exogenous HTT2 increased the survival rates of heat-shocked heading Chinese cabbage by promoting thermotolerance through decreasing electrical conductivity and extending hypocotyl length. Our work provides a new approach to the genetic manipulation of thermotolerance in crops through the introduction of exogenous thermotolerance genes.}, } @article {pmid29925320, year = {2018}, author = {Prinsi, B and Negri, AS and Failla, O and Scienza, A and Espen, L}, title = {Root proteomic and metabolic analyses reveal specific responses to drought stress in differently tolerant grapevine rootstocks.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {126}, pmid = {29925320}, issn = {1471-2229}, mesh = {Dehydration ; Metabolic Networks and Pathways ; Metabolomics ; Oxidation-Reduction ; Plant Growth Regulators/metabolism/physiology ; Plant Proteins/metabolism/physiology ; Plant Roots/*metabolism/physiology ; Proteomics ; Vitis/*metabolism/physiology ; }, abstract = {BACKGROUND: Roots play a central role in plant response to water stress (WS). They are involved in its perception and signalling to the leaf as well as in allowing the plant to adapt to maintaining an adequate water balance. Only a few studies have investigated the molecular/biochemical responses to WS in roots of perennial plants, such as grapevine. This study compares two grapevine rootstock genotypes (i.e. 101.14 and M4) with different tolerance to WS, evaluating the responses at proteomic and metabolite levels.

RESULTS: WS induced changes in the abundance of several proteins in both genotypes (17 and 22% of the detected proteins in 101.14 and M4, respectively). The proteomic analysis revealed changes in many metabolic pathways that fitted well with the metabolite data. M4 showed metabolic responses which were potentially able to counteract the WS effects, such as the drop in cell turgor, increased oxidative stress and loss of cell structure integrity/functionality. However, in 101.14 it was evident that the roots were suffering more severely from these effects. We found that many proteins classified as active in energy metabolism, hormone metabolism, protein, secondary metabolism and stress functional classes showed particular differences between the two rootstocks.

CONCLUSION: The proteomic/metabolite comparative analysis carried out provides new information on the possible biochemical and molecular strategies adopted by grapevine roots to counteract WS. Although further work is needed to define in detail the role(s) of the proteins and metabolites that characterize WS response, this study, involving the M4 rootstock genotype, highlights that osmotic responses, modulations of C metabolism, mitochondrial functionality and some specific responses to stress occurring in the roots play a primary role in Vitis spp. tolerance to this type of abiotic stress.}, } @article {pmid29925319, year = {2018}, author = {Peng, Z and He, S and Gong, W and Xu, F and Pan, Z and Jia, Y and Geng, X and Du, X}, title = {Integration of proteomic and transcriptomic profiles reveals multiple levels of genetic regulation of salt tolerance in cotton.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {128}, pmid = {29925319}, issn = {1471-2229}, support = {2016YFD0100203//the National Key Research and Development Program, the Ministry of Science and Technology/ ; 2013BAD01B03//the National Science and Technology Support Program/ ; }, mesh = {Gene Expression Regulation, Plant/genetics ; Genes, Plant/genetics/physiology ; Gossypium/*genetics/metabolism/physiology ; Mass Spectrometry ; MicroRNAs/genetics/physiology ; Plant Proteins/genetics/physiology ; Proteomics ; Salt Tolerance ; Salt-Tolerant Plants/genetics/metabolism/physiology ; Transcriptome ; }, abstract = {BACKGROUND: Salinity is a major abiotic stress that limits upland cotton growth and reduces fibre production worldwide. To reveal genetic regulation via transcript and protein levels after salt stress, we comprehensively analysed the global changes in mRNA, miRNA, and protein profiles in response to salt stress in two contrasting salt-tolerant cotton genotypes.

RESULTS: In the current study, proteomic and mRNA-seq data were combined to reveal that some genes are differentially expressed at both the proteomic and mRNA levels. However, we observed no significant change in mRNA corresponding to most of the strongly differentially abundant proteins. This finding may have resulted from global changes in alternative splicing events and miRNA levels under salt stress conditions. Evidence was provided indicating that several salt stress-responsive proteins can alter miRNAs and modulate alternative splicing events in upland cotton. The results of the stringent screening of the mRNA-seq and proteomic data between the salt-tolerant and salt-sensitive genotypes identified 63 and 85 candidate genes/proteins related to salt tolerance after 4 and 24 h of salt stress, respectively, between the tolerant and sensitive genotype. Finally, we predicted an interaction network comprising 158 genes/proteins and then discovered that two main clusters in the network were composed of ATP synthase (CotAD_74681) and cytochrome oxidase (CotAD_46197) in mitochondria. The results revealed that mitochondria, as important organelles involved in energy metabolism, play an essential role in the synthesis of resistance proteins during the process of salt exposure.

CONCLUSION: We provided a plausible schematic for the systematic salt tolerance model; this schematic reveals multiple levels of gene regulation in response to salt stress in cotton and provides a list of salt tolerance-related genes/proteins. The information here will facilitate candidate gene discovery and molecular marker development for salt tolerance breeding in cotton.}, } @article {pmid29925317, year = {2018}, author = {Zhang, H and Wang, H and Zhu, Q and Gao, Y and Wang, H and Zhao, L and Wang, Y and Xi, F and Wang, W and Yang, Y and Lin, C and Gu, L}, title = {Transcriptome characterization of moso bamboo (Phyllostachys edulis) seedlings in response to exogenous gibberellin applications.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {125}, pmid = {29925317}, issn = {1471-2229}, support = {2018YFD060002//National Key Research and Development Program of China/ ; 2016YFD0600106//National Key Research and Development Program of China/ ; 31570674//National Natural Science Foundation of China/ ; 125/KLA15001E//Fujian Innovative Center for Germplasm Resources and Cultivation of Woody plants/ ; KXGH1701//International Science and Technology Cooperation and Exchange Fund from Fujian Agriculture and Forestry University/ ; }, mesh = {Cell Wall/genetics ; Gene Expression Regulation, Plant/drug effects ; Genes, Plant/genetics/physiology ; Gibberellins/*pharmacology ; Photosynthesis/drug effects ; Plant Growth Regulators/*pharmacology ; Sasa/*drug effects/genetics/growth & development/metabolism ; Seedlings/*drug effects/genetics/metabolism ; Signal Transduction/drug effects ; Transcriptome/drug effects ; }, abstract = {BACKGROUND: Moso bamboo (Phyllostachys edulis) is a well-known bamboo species of high economic value in the textile industry due to its rapid growth. Phytohormones, which are master regulators of growth and development, serve as important endogenous signals. However, the mechanisms through which phytohormones regulate growth in moso bamboo remain unknown to date.

RESULTS: Here, we reported that exogenous gibberellins (GA) applications resulted in a significantly increased internode length and lignin condensation. Transcriptome sequencing revealed that photosynthesis-related genes were enriched in the GA-repressed gene class, which was consistent with the decrease in leaf chlorophyll concentrations and the lower rate of photosynthesis following GA treatment. Exogenous GA applications on seedlings are relatively easy to perform, thus we used 4-week-old whole seedlings of bamboo for GA- treatment followed by high throughput sequencing. In this study, we identified 932 cis-nature antisense transcripts (cis-NATs), and 22,196 alternative splicing (AS) events in total. Among them, 42 cis-nature antisense transcripts (cis-NATs) and 442 AS events were differentially expressed upon exposure to exogenous GA3, suggesting that post-transcriptional regulation might be also involved in the GA3 response. Targets of differential expression of cis-NATs included genes involved in hormone receptor, photosynthesis and cell wall biogenesis. For example, LAC4 and its corresponding cis-NATs were GA3-induced, and may be involved in the accumulation of lignin, thus affecting cell wall composition.

CONCLUSIONS: This study provides novel insights illustrating how GA alters post-transcriptional regulation and will shed light on the underlying mechanism of growth modulated by GA in moso bamboo.}, } @article {pmid29925315, year = {2018}, author = {Coombe, L and Zhang, J and Vandervalk, BP and Chu, J and Jackman, SD and Birol, I and Warren, RL}, title = {ARKS: chromosome-scale scaffolding of human genome drafts with linked read kmers.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {234}, pmid = {29925315}, issn = {1471-2105}, support = {R01 HG007182/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: The long-range sequencing information captured by linked reads, such as those available from 10× Genomics (10xG), helps resolve genome sequence repeats, and yields accurate and contiguous draft genome assemblies. We introduce ARKS, an alignment-free linked read genome scaffolding methodology that uses linked reads to organize genome assemblies further into contiguous drafts. Our approach departs from other read alignment-dependent linked read scaffolders, including our own (ARCS), and uses a kmer-based mapping approach. The kmer mapping strategy has several advantages over read alignment methods, including better usability and faster processing, as it precludes the need for input sequence formatting and draft sequence assembly indexing. The reliance on kmers instead of read alignments for pairing sequences relaxes the workflow requirements, and drastically reduces the run time.

RESULTS: Here, we show how linked reads, when used in conjunction with Hi-C data for scaffolding, improve a draft human genome assembly of PacBio long-read data five-fold (baseline vs. ARKS NG50 = 4.6 vs. 23.1 Mbp, respectively). We also demonstrate how the method provides further improvements of a megabase-scale Supernova human genome assembly (NG50 = 14.74 Mbp vs. 25.94 Mbp before and after ARKS), which itself exclusively uses linked read data for assembly, with an execution speed six to nine times faster than competitive linked read scaffolders (~ 10.5 h compared to 75.7 h, on average). Following ARKS scaffolding of a human genome 10xG Supernova assembly (of cell line NA12878), fewer than 9 scaffolds cover each chromosome, except the largest (chromosome 1, n = 13).

CONCLUSIONS: ARKS uses a kmer mapping strategy instead of linked read alignments to record and associate the barcode information needed to order and orient draft assembly sequences. The simplified workflow, when compared to that of our initial implementation, ARCS, markedly improves run time performances on experimental human genome datasets. Furthermore, the novel distance estimator in ARKS utilizes barcoding information from linked reads to estimate gap sizes. It accomplishes this by modeling the relationship between known distances of a region within contigs and calculating associated Jaccard indices. ARKS has the potential to provide correct, chromosome-scale genome assemblies, promptly. We expect ARKS to have broad utility in helping refine draft genomes.}, } @article {pmid29925314, year = {2018}, author = {Crowgey, EL and Marsh, AG and Robinson, KG and Yeager, SK and Akins, RE}, title = {Epigenetic machine learning: utilizing DNA methylation patterns to predict spastic cerebral palsy.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {225}, pmid = {29925314}, issn = {1471-2105}, support = {U54 GM104941/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Spastic cerebral palsy (CP) is a leading cause of physical disability. Most people with spastic CP are born with it, but early diagnosis is challenging, and no current biomarker platform readily identifies affected individuals. The aim of this study was to evaluate epigenetic profiles as biomarkers for spastic CP. A novel analysis pipeline was employed to assess DNA methylation patterns between peripheral blood cells of adolescent subjects (14.9 ± 0.3 years old) with spastic CP and controls at single CpG site resolution.

RESULTS: Significantly hypo- and hyper-methylated CpG sites associated with spastic CP were identified. Nonmetric multidimensional scaling fully discriminated the CP group from the controls. Machine learning based classification modeling indicated a high potential for a diagnostic model, and 252 sets of 40 or fewer CpG sites achieved near-perfect accuracy within our adolescent cohorts. A pilot test on significantly younger subjects (4.0 ± 1.5 years old) identified subjects with 73% accuracy.

CONCLUSIONS: Adolescent patients with spastic CP can be distinguished from a non-CP cohort based on DNA methylation patterns in peripheral blood cells. A clinical diagnostic test utilizing a panel of CpG sites may be possible using a simulated classification model. A pilot validation test on patients that were more than 10 years younger than the main adolescent cohorts indicated that distinguishing methylation patterns are present earlier in life. This study is the first to report an epigenetic assay capable of distinguishing a CP cohort.}, } @article {pmid29925313, year = {2018}, author = {Dluge, KL and Song, Z and Wang, B and Tyler Steede, W and Xiao, B and Liu, Y and Dewey, RE}, title = {Characterization of Nicotiana tabacum genotypes possessing deletion mutations that affect potyvirus resistance and the production of trichome exudates.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {484}, pmid = {29925313}, issn = {1471-2164}, support = {761008//Yunnan Academy of Tobacco Agricultural Sciences/ ; }, mesh = {Chromosomes, Human, Pair 21/genetics ; Exudates and Transudates ; Gene Expression Regulation, Plant/genetics ; Genotype ; Humans ; Plant Proteins/genetics ; Plants, Genetically Modified/*genetics ; Potyvirus/genetics ; Tobacco/*genetics ; Trichomes/genetics ; }, abstract = {BACKGROUND: Advances in genomics technologies are making it increasingly feasible to characterize breeding lines that carry traits of agronomic interest. Tobacco germplasm lines that carry loci designated VAM and va have been extensively investigated due to their association with potyvirus resistance (both VAM and va) and defects in leaf surface compounds originating from glandular trichomes (VAM only). Molecular studies and classical genetic analyses are consistent with the model that VAM and va represent deletion mutations in the same chromosomal region. In this study, we used RNA-seq analysis, together with emerging tobacco reference genome sequence information to characterize the genomic regions deleted in tobacco lines containing VAM and va.

RESULTS: Tobacco genotypes TI 1406 (VAM), K326-va and K326 (wild type) were analyzed using RNA-seq to generate a list of genes differentially expressed in TI 1406 and K326-va, versus the K326 control. Candidate genes were localized onto tobacco genome scaffolds and validated as being absent in only VAM, or missing in both VAM and va, through PCR analysis. These results enabled the construction of a map that predicted the relative extent of the VAM and va mutations on the distal end of chromosome 21. The RNA-seq analyses lead to the discovery that members of the cembratrienol synthase gene family are deleted in TI 1406. Transformation of TI 1406 with a cembratrienol synthase cDNA, however, did not recover the leaf chemistry phenotype. Common to both TI 1406 and K326-va was the absence of a gene encoding a specific isoform of a eukaryotic translation initiation factor (eiF4E1.S). Transformation experiments showed that ectopic expression of eiF4E1.S is sufficient to restore potyvirus susceptibility in plants possessing either the va or VAM mutant loci.

CONCLUSIONS: We have demonstrated the feasibility of using RNA-seq and emerging whole genome sequence resources in tobacco to characterize the VAM and va deletion mutants. These results lead to the discovery of genes underlying some of the phenotypic traits associated with these historically important loci. Additionally, initial size estimations were made for the deleted regions, and dominant markers were developed that are very close to one of the deletion junctions that defines va.}, } @article {pmid29925311, year = {2018}, author = {Foley, JF and Phadke, DP and Hardy, O and Hardy, S and Miller, V and Madan, A and Howard, K and Kruse, K and Lord, C and Ramaiahgari, S and Solomon, GG and Shah, RR and Pandiri, AR and Herbert, RA and Sills, RC and Merrick, BA}, title = {Whole exome sequencing in the rat.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {487}, pmid = {29925311}, issn = {1471-2164}, support = {HHSN273201500005C/ES/NIEHS NIH HHS/United States ; HHSN273201500005I/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Exome/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mice ; Rats ; Sequence Analysis, DNA/methods ; Tissue Fixation ; Whole Exome Sequencing/*methods ; }, abstract = {BACKGROUND: The rat genome was sequenced in 2004 with the aim to improve human health altered by disease and environmental influences through gene discovery and animal model validation. Here, we report development and testing of a probe set for whole exome sequencing (WES) to detect sequence variants in exons and UTRs of the rat genome. Using an in-silico approach, we designed probes targeting the rat exome and compared captured mutations in cancer-related genes from four chemically induced rat tumor cell lines (C6, FAT7, DSL-6A/C1, NBTII) to validated cancer genes in the human database, Catalogue of Somatic Mutations in Cancer (COSMIC) as well as normal rat DNA. Paired, fresh frozen (FF) and formalin-fixed, paraffin-embedded (FFPE) liver tissue from naive rats were sequenced to confirm known dbSNP variants and identify any additional variants.

RESULTS: Informatics analysis of available gene annotation from rat RGSC6.0/rn6 RefSeq and Ensembl transcripts provided 223,636 unique exons representing a total of 26,365 unique genes and untranslated regions. Using this annotation and the Rn6 reference genome, an in-silico probe design generated 826,878 probe sequences of which 94.2% were uniquely aligned to the rat genome without mismatches. Further informatics analysis revealed 25,249 genes (95.8%) covered by at least one probe and 23,603 genes (93.5%) had every exon covered by one or more probes. We report high performance metrics from exome sequencing of our probe set and Sanger validation of annotated, highly relevant, cancer gene mutations as cataloged in the human COSMIC database, in addition to several exonic variants in cancer-related genes.

CONCLUSIONS: An in-silico probe set was designed to enrich the rat exome from isolated DNA. The platform was tested on rat tumor cell lines and normal FF and FFPE liver tissue. The method effectively captured target exome regions in the test DNA samples with exceptional sensitivity and specificity to obtain reliable sequencing data representing variants that are likely chemically induced somatic mutations. Genomic discovery conducted by means of high throughput WES queries should benefit investigators in discovering rat genomic variants in disease etiology and in furthering human translational research.}, } @article {pmid29925310, year = {2018}, author = {Chang, WH and Lai, AG}, title = {Mixed evolutionary origins of endogenous biomass-depolymerizing enzymes in animals.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {483}, pmid = {29925310}, issn = {1471-2164}, support = {LT0241/2014-L//Human Frontier Science Program/ ; ALTF 1154-2013//European Molecular Biology Organization/ ; }, mesh = {Animals ; Biofuels ; Gene Transfer, Horizontal/genetics ; Genomics/*methods ; Glycoside Hydrolases/*genetics ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Animals are thought to achieve lignocellulose digestion via symbiotic associations with gut microbes; this view leads to significant focus on bacteria and fungi for lignocellulolytic systems. The presence of biomass conversion systems hardwired into animal genomes has not yet been unequivocally demonstrated.

RESULTS: We perform an exhaustive search for glycoside hydrolase (GH) genes from 21 genomes representing major bilaterian (Ecdysozoa, Spiralia, Echinodermata and Chordata) and basal metazoan (Porifera and Cnidaria) lineages. We also assessed the genome of a unicellular relative of Metazoa, Capsaspora owczarzaki and together with comparative analyses on 126 crustacean transcriptomes, we found that animals are living bioreactors at a microscale as they encode enzymatic suites for biomass decomposition. We identified a total of 16,723 GH homologs (2373 genes from animal genomes and 14,350 genes from crustacean transcriptomes) that are further classified into 60 GH families. Strikingly, through phylogenetic analyses, we observed that animal lignocellulosic enzymes have multiple origins, either inherited vertically over millions of years from a common ancestor or acquired more recently from non-animal organisms.

CONCLUSION: We have conducted a systematic and comprehensive survey of GH genes across major animal lineages. The ability of biomass decay appears to be determined by animals' dietary strategies. Detritivores have genes that accomplish broad enzymatic functions while the number of GH families is reduced in animals that have evolved specialized diets. Animal GH candidates identified in this study will not only facilitate future functional genomics research but also provide an analysis platform to identify enzyme candidates with industrial potential.}, } @article {pmid29925309, year = {2018}, author = {Zhang, X and Wang, B and Zhang, L and You, G and Palais, RA and Zhou, L and Fu, Q}, title = {Accurate diagnosis of spinal muscular atrophy and 22q11.2 deletion syndrome using limited deoxynucleotide triphosphates and high-resolution melting.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {485}, pmid = {29925309}, issn = {1471-2164}, support = {No.81371893//the National Natural Science Foundation of China/ ; 18YF1414800//Shanghai Sailing Program/ ; SHDC12017109//Shen Kang municipal hospital emerging frontier technology joint research project/ ; TM201615//Translational Medicine Collaborative Innovation research project of Shanghai Jiao Tong University School of Medicine/ ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics ; Chromosomes, Human, Pair 22/*genetics ; Clathrin Heavy Chains/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/genetics ; DNA Copy Number Variations/*genetics ; DiGeorge Syndrome/*genetics ; Humans ; Minor Histocompatibility Antigens/genetics ; Muscular Atrophy, Spinal/*diagnosis/*genetics ; Phosphotransferases (Alcohol Group Acceptor)/genetics ; Survival of Motor Neuron 1 Protein/genetics ; }, abstract = {BACKGROUND: Copy number variation (CNV) has been implicated in the genetics of multiple human diseases. Spinal muscular atrophy (SMA) and 22q11.2 deletion syndrome (22q11.2DS) are two of the most common diseases which are caused by DNA copy number variations. Genetic diagnostics for these conditions would be enhanced by more accurate and efficient methods to detect the relevant CNVs.

METHODS: Competitive PCR with limited deoxynucleotide triphosphates (dNTPs) and high-resolution melting (HRM) analysis was used to detect 22q11.2DS, SMA and SMA carrier status. For SMA, we focused on the copy number of SMN1 gene. For 22q11.2DS, we analyzed CNV for 3 genes (CLTCL1, KLHL22, and PI4KA) which are located between different region-specific low copy repeats. CFTR was used as internal reference gene for all targets. Short PCR products with separated Tms were designed by uMelt software.

RESULTS: One hundred three clinical patient samples were pretested for possible SMN1 CNV, including carrier status, using multiplex ligation-dependent probe amplification (MLPA) commercial kit as gold standard. Ninety-nine samples consisting of 56 wild-type and 43 22q11.2DS samples were analyzed for CLTCL1, KLHL22, and PI4KA CNV also using MLPA. These samples were blinded and re-analyzed for the same CNVs using the limited dNTPs PCR with HRM analysis and the results were completely consistent with MLPA.

CONCLUSIONS: Limited dNTPs PCR with HRM analysis is an accurate method for detecting SMN1 and 22q11.2 CNVs. This method can be used quickly, reliably, and economically in large population screening for these diseases.}, } @article {pmid29925308, year = {2018}, author = {Bassim, S and Allam, B}, title = {SNP hot-spots in the clam parasite QPX.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {486}, pmid = {29925308}, issn = {1471-2164}, support = {R/FBM-36//National Sea Grant College Program of NOAA/ ; #2637//Gordon and Betty Moore Foundation (US)/ ; ACI-1548562//Extreme Science and Engineering Discovery Environment (XSEDE)/ ; }, mesh = {Adaptation, Physiological/genetics ; Animals ; DNA Copy Number Variations/*genetics ; Mutation/genetics ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide/*genetics ; Software ; United States ; Virulence ; }, abstract = {BACKGROUND: Quahog Parasite Unknown (QPX) is an opportunistic protistan pathogen of the clam Mercenaria mercenaria. Infections with QPX have caused significant economic losses in the Northeastern United States. Previous research demonstrated a geographic gradient for disease prevalence and intensity, but little information is available on the genetic diversity of the parasite throughout its distribution range. Also, QPX virulence factors are not well understood. This study addresses the occurrence of QPX genetic variants with a particular focus on functions involved in virulence and adaptation to environmental conditions.

RESULTS: Analyses were performed using transcriptome-wide single-nucleotide polymorphism (SNP) of four QPX isolates cultured from infected clams collected from disparate locations along the Northeastern United States. For contig assembly and mapping, two different genome builds and four transcriptomes of the parasite were examined. Genomic variants appeared at a differential rate relative to sequenced transcripts at 20.18 and 22.55% occurrence under 1000 base pairs upstream and downstream protein domains respectively and at 57.26% rate in protein domain coding sequences. QPX strains shared 30.50% of the mutations and exhibited a preferential nucleotide substitution towards thymine. Sequence identity suggested relatedness between different QPX strains, with the parasite being possibly introduced to Virginia from the Massachusetts region during clam trading, while QPX could have been naturally present in New York. Diversity in virulence, temperature, and salinity domains suggested a common variability between strains, but with a preferential higher variation in local adaptation genes. This could explain differences in disease prevalence noted in different regions. Overall, the results supported views that this opportunistic parasite might be able to adapt to varying environmental conditions.

CONCLUSION: Relatedness and mutations between the four QPX strains suggested that variability in environmental-related functions favors parasite survival, potentially promoting resilience against stressful conditions. These findings are in agreement with the widespread presence of QPX in the environment. Although QPX levels are enzootic in most areas, an increase in disease outbreaks were often associated with seasonal changes in environmental conditions. A selection mediated by the parasitic life of QPX remains possible, but the effect of the environment on the biology of the parasite appears more obvious.}, } @article {pmid29925307, year = {2018}, author = {Babic, J and Griscom, L and Cramer, J and Coudreuse, D}, title = {An easy-to-build and re-usable microfluidic system for live-cell imaging.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {8}, pmid = {29925307}, issn = {1471-2121}, mesh = {Cell Survival ; Elastomers/chemistry ; Fluorescence ; HeLa Cells ; Humans ; *Imaging, Three-Dimensional ; Microfluidics/*methods ; Perfusion ; Pressure ; Rheology ; Saccharomyces cerevisiae/metabolism ; Temperature ; }, abstract = {BACKGROUND: Real-time monitoring of cellular responses to dynamic changes in their environment or to specific treatments has become central to cell biology. However, when coupled to live-cell imaging, such strategies are difficult to implement with precision and high time resolution, and the simultaneous alteration of multiple parameters is a major challenge. Recently, microfluidics has provided powerful solutions for such analyses, bringing an unprecedented level of control over the conditions and the medium in which cells under microscopic observation are grown. However, such technologies have remained under-exploited, largely as a result of the complexity associated with microfabrication procedures.

RESULTS: In this study, we have developed simple but powerful microfluidic devices dedicated to live-cell imaging. These microsystems take advantage of a robust elastomer that is readily available to researchers and that presents excellent bonding properties, in particular to microscopy-grade glass coverslips. Importantly, the chips are easy-to-build without sophisticated equipment, and they are compatible with the integration of complex, customized fluidic networks as well as with the multiplexing of independent assays on a single device. We show that the chips are re-usable, a significant advantage for the popularization of microfluidics in cell biology. Moreover, we demonstrate that they allow for the dynamic, accurate and simultaneous control of multiple parameters of the cellular environment.

CONCLUSIONS: While they do not possess all the features of the microdevices that are built using complex and costly procedures, the simplicity and versatility of the chips that we have developed make them an attractive alternative for a range of applications. The emergence of such devices, which can be fabricated and used by any laboratory, will provide the possibility for a larger number of research teams to take full advantage of these new methods for investigating cell biology.}, } @article {pmid29925267, year = {2018}, author = {Brautigan, DL and Shenolikar, S}, title = {Protein Serine/Threonine Phosphatases: Keys to Unlocking Regulators and Substrates.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {921-964}, doi = {10.1146/annurev-biochem-062917-012332}, pmid = {29925267}, issn = {1545-4509}, abstract = {Protein serine/threonine phosphatases (PPPs) are ancient enzymes, with distinct types conserved across eukaryotic evolution. PPPs are segregated into types primarily on the basis of the unique interactions of PPP catalytic subunits with regulatory proteins. The resulting holoenzymes dock substrates distal to the active site to enhance specificity. This review focuses on the subunit and substrate interactions for PPP that depend on short linear motifs. Insights about these motifs from structures of holoenzymes open new opportunities for computational biology approaches to elucidate PPP networks. There is an expanding knowledge base of posttranslational modifications of PPP catalytic and regulatory subunits, as well as of their substrates, including phosphorylation, acetylation, and ubiquitination. Cross talk between these posttranslational modifications creates PPP-based signaling. Knowledge of PPP complexes, signaling clusters, as well as how PPPs communicate with each other in response to cellular signals should unlock the doors to PPP networks and signaling "clouds" that orchestrate and coordinate different aspects of cell physiology.}, } @article {pmid29925266, year = {2018}, author = {von Heijne, G}, title = {Protein Evolution and Design.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {101-103}, doi = {10.1146/annurev-biochem-062917-012013}, pmid = {29925266}, issn = {1545-4509}, abstract = {This article introduces the Protein Evolution and Design theme of the Annual Review of Biochemistry Volume 87.}, } @article {pmid29925265, year = {2018}, author = {Tsai, S(}, title = {The Structural Enzymology of Iterative Aromatic Polyketide Synthases: A Critical Comparison with Fatty Acid Synthases.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {503-531}, doi = {10.1146/annurev-biochem-063011-164509}, pmid = {29925265}, issn = {1545-4509}, abstract = {Polyketides are a large family of structurally complex natural products including compounds with important bioactivities. Polyketides are biosynthesized by polyketide synthases (PKSs), multienzyme complexes derived evolutionarily from fatty acid synthases (FASs). The focus of this review is to critically compare the properties of FASs with iterative aromatic PKSs, including type II PKSs and fungal type I nonreducing PKSs whose chemical logic is distinct from that of modular PKSs. This review focuses on structural and enzymological studies that reveal both similarities and striking differences between FASs and aromatic PKSs. The potential application of FAS and aromatic PKS structures for bioengineering future drugs and biofuels is highlighted.}, } @article {pmid29925264, year = {2018}, author = {Choi, J and Grosely, R and Prabhakar, A and Lapointe, CP and Wang, J and Puglisi, JD}, title = {How Messenger RNA and Nascent Chain Sequences Regulate Translation Elongation.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {421-449}, doi = {10.1146/annurev-biochem-060815-014818}, pmid = {29925264}, issn = {1545-4509}, support = {T32 GM008294/GM/NIGMS NIH HHS/United States ; }, abstract = {Translation elongation is a highly coordinated, multistep, multifactor process that ensures accurate and efficient addition of amino acids to a growing nascent-peptide chain encoded in the sequence of translated messenger RNA (mRNA). Although translation elongation is heavily regulated by external factors, there is clear evidence that mRNA and nascent-peptide sequences control elongation dynamics, determining both the sequence and structure of synthesized proteins. Advances in methods have driven experiments that revealed the basic mechanisms of elongation as well as the mechanisms of regulation by mRNA and nascent-peptide sequences. In this review, we highlight how mRNA and nascent-peptide elements manipulate the translation machinery to alter the dynamics and pathway of elongation.}, } @article {pmid29925263, year = {2018}, author = {Suganuma, T and Workman, JL}, title = {Chromatin and Metabolism.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {27-49}, doi = {10.1146/annurev-biochem-062917-012634}, pmid = {29925263}, issn = {1545-4509}, abstract = {Chromatin is a mighty consumer of cellular energy generated by metabolism. Metabolic status is efficiently coordinated with transcription and translation, which also feed back to regulate metabolism. Conversely, suppression of energy utilization by chromatin processes may serve to preserve energy resources for cell survival. Most of the reactions involved in chromatin modification require metabolites as their cofactors or coenzymes. Therefore, the metabolic status of the cell can influence the spectra of posttranslational histone modifications and the structure, density and location of nucleosomes, impacting epigenetic processes. Thus, transcription, translation, and DNA/RNA biogenesis adapt to cellular metabolism. In addition to dysfunctions of metabolic enzymes, imbalances between metabolism and chromatin activities trigger metabolic disease and life span alteration. Here, we review the synthesis of the metabolites and the relationships between metabolism and chromatin function. Furthermore, we discuss how the chromatin response feeds back to metabolic regulation in biological processes.}, } @article {pmid29925262, year = {2018}, author = {Niedernhofer, LJ and Gurkar, AU and Wang, Y and Vijg, J and Hoeijmakers, JHJ and Robbins, PD}, title = {Nuclear Genomic Instability and Aging.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {295-322}, doi = {10.1146/annurev-biochem-062917-012239}, pmid = {29925262}, issn = {1545-4509}, abstract = {The nuclear genome decays as organisms age. Numerous studies demonstrate that the burden of several classes of DNA lesions is greater in older mammals than in young mammals. More challenging is proving this is a cause rather than a consequence of aging. The DNA damage theory of aging, which argues that genomic instability plays a causal role in aging, has recently gained momentum. Support for this theory stems partly from progeroid syndromes in which inherited defects in DNA repair increase the burden of DNA damage leading to accelerated aging of one or more organs. Additionally, growing evidence shows that DNA damage accrual triggers cellular senescence and metabolic changes that promote a decline in tissue function and increased susceptibility to age-related diseases. Here, we examine multiple lines of evidence correlating nuclear DNA damage with aging. We then consider how, mechanistically, nuclear genotoxic stress could promote aging. We conclude that the evidence, in toto, supports a role for DNA damage as a nidus of aging.}, } @article {pmid29925261, year = {2018}, author = {Enam, C and Geffen, Y and Ravid, T and Gardner, RG}, title = {Protein Quality Control Degradation in the Nucleus.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {725-749}, doi = {10.1146/annurev-biochem-062917-012730}, pmid = {29925261}, issn = {1545-4509}, abstract = {Nuclear proteins participate in diverse cellular processes, many of which are essential for cell survival and viability. To maintain optimal nuclear physiology, the cell employs the ubiquitin-proteasome system to eliminate damaged and misfolded proteins in the nucleus that could otherwise harm the cell. In this review, we highlight the current knowledge about the major ubiquitin-protein ligases involved in protein quality control degradation (PQCD) in the nucleus and how they orchestrate their functions to eliminate misfolded proteins in different nuclear subcompartments. Many human disorders are causally linked to protein misfolding in the nucleus, hence we discuss major concepts that still need to be clarified to better understand the basis of the nuclear misfolded proteins' toxic effects. Additionally, we touch upon potential strategies for manipulating nuclear PQCD pathways to ameliorate diseases associated with protein misfolding and aggregation in the nucleus.}, } @article {pmid29925260, year = {2018}, author = {Zygiel, EM and Nolan, EM}, title = {Transition Metal Sequestration by the Host-Defense Protein Calprotectin.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {621-643}, pmid = {29925260}, issn = {1545-4509}, support = {R01 GM118695/GM/NIGMS NIH HHS/United States ; R01 GM126376/GM/NIGMS NIH HHS/United States ; }, abstract = {In response to microbial infection, the human host deploys metal-sequestering host-defense proteins, which reduce nutrient availability and thereby inhibit microbial growth and virulence. Calprotectin (CP) is an abundant antimicrobial protein released from neutrophils and epithelial cells at sites of infection. CP sequesters divalent first-row transition metal ions to limit the availability of essential metal nutrients in the extracellular space. While functional and clinical studies of CP have been pursued for decades, advances in our understanding of its biological coordination chemistry, which is central to its role in the host-microbe interaction, have been made in more recent years. In this review, we focus on the coordination chemistry of CP and highlight studies of its metal-binding properties and contributions to the metal-withholding innate immune response. Taken together, these recent studies inform our current model of how CP participates in metal homeostasis and immunity, and they provide a foundation for further investigations of a remarkable metal-chelating protein at the host-microbe interface and beyond.}, } @article {pmid29925259, year = {2018}, author = {Noda-Garcia, L and Liebermeister, W and Tawfik, DS}, title = {Metabolite-Enzyme Coevolution: From Single Enzymes to Metabolic Pathways and Networks.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {187-216}, doi = {10.1146/annurev-biochem-062917-012023}, pmid = {29925259}, issn = {1545-4509}, abstract = {How individual enzymes evolved is relatively well understood. However, individual enzymes rarely confer a physiological advantage on their own. Judging by its current state, the emergence of metabolism seemingly demanded the simultaneous emergence of many enzymes. Indeed, how multicomponent interlocked systems, like metabolic pathways, evolved is largely an open question. This complexity can be unlocked if we assume that survival of the fittest applies not only to genes and enzymes but also to the metabolites they produce. This review develops our current knowledge of enzyme evolution into a wider hypothesis of pathway and network evolution. We describe the current models for pathway evolution and offer an integrative metabolite-enzyme coevolution hypothesis. Our hypothesis addresses the origins of new metabolites and of new enzymes and the order of their recruitment. We aim to not only survey established knowledge but also present open questions and potential ways of addressing them.}, } @article {pmid29925258, year = {2018}, author = {Weis, WI and Kobilka, BK}, title = {The Molecular Basis of G Protein-Coupled Receptor Activation.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {897-919}, doi = {10.1146/annurev-biochem-060614-033910}, pmid = {29925258}, issn = {1545-4509}, abstract = {G protein-coupled receptors (GPCRs) mediate the majority of cellular responses to external stimuli. Upon activation by a ligand, the receptor binds to a partner heterotrimeric G protein and promotes exchange of GTP for GDP, leading to dissociation of the G protein into α and βγ subunits that mediate downstream signals. GPCRs can also activate distinct signaling pathways through arrestins. Active states of GPCRs form by small rearrangements of the ligand-binding, or orthosteric, site that are amplified into larger conformational changes. Molecular understanding of the allosteric coupling between ligand binding and G protein or arrestin interaction is emerging from structures of several GPCRs crystallized in inactive and active states, spectroscopic data, and computer simulations. The coupling is loose, rather than concerted, and agonist binding does not fully stabilize the receptor in an active conformation. Distinct intermediates whose populations are shifted by ligands of different efficacies underlie the complex pharmacology of GPCRs.}, } @article {pmid29925257, year = {2018}, author = {Gazit, E}, title = {Reductionist Approach in Peptide-Based Nanotechnology.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {533-553}, doi = {10.1146/annurev-biochem-062917-012541}, pmid = {29925257}, issn = {1545-4509}, abstract = {The formation of ordered nanostructures by molecular self-assembly of proteins and peptides represents one of the principal directions in nanotechnology. Indeed, polyamides provide superior features as materials with diverse physical properties. A reductionist approach allowed the identification of extremely short peptide sequences, as short as dipeptides, which could form well-ordered amyloid-like β-sheet-rich assemblies comparable to supramolecular structures made of much larger proteins. Some of the peptide assemblies show remarkable mechanical, optical, and electrical characteristics. Another direction of reductionism utilized a natural noncoded amino acid, α-aminoisobutryic acid, to form short superhelical assemblies. The use of this exceptional helix inducer motif allowed the fabrication of single heptad repeats used in various biointerfaces, including their use as surfactants and DNA-binding agents. Two additional directions of the reductionist approach include the use of peptide nucleic acids (PNAs) and coassembly techniques. The diversified accomplishments of the reductionist approach, as well as the exciting future advances it bears, are discussed.}, } @article {pmid29925256, year = {2018}, author = {Kornfeld, S}, title = {A Lifetime of Adventures in Glycobiology.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {1-21}, doi = {10.1146/annurev-biochem-062917-011911}, pmid = {29925256}, issn = {1545-4509}, abstract = {My initial research experience involved studying how bacteria synthesize nucleotide sugars, the donors for the formation of cell wall polysaccharides. During this time, I became aware that mammalian cells also have a surface coat of sugars and was intrigued as to whether these sugars might be arranged in specific sequences that function as information molecules in biologic processes. Thus began a long journey that has taken me from glycan structural analysis and determination of plant lectin-binding preferences to the biosynthesis of Asn-linked oligosaccharides and the mannose 6-phosphate (Man-6-P) lysosomal enzyme targeting pathway. The Man-6-P system represents an early example of a glycan serving as an information molecule in a fundamental cellular function. The remarkable advances in the field of glycobiology since I entered have uncovered scores of additional examples of oligosaccharide-lectin interactions mediating critical biologic processes. It has been a rewarding experience to participate in the efforts that have established a central role for glycans in biology.}, } @article {pmid29925255, year = {2018}, author = {Bridwell-Rabb, J and Grell, TAJ and Drennan, CL}, title = {A Rich Man, Poor Man Story of S-Adenosylmethionine and Cobalamin Revisited.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {555-584}, doi = {10.1146/annurev-biochem-062917-012500}, pmid = {29925255}, issn = {1545-4509}, abstract = {S-adenosylmethionine (AdoMet) has been referred to as both "a poor man's adenosylcobalamin (AdoCbl)" and "a rich man's AdoCbl," but today, with the ever-increasing number of functions attributed to each cofactor, both appear equally rich and surprising. The recent characterization of an organometallic species in an AdoMet radical enzyme suggests that the line that differentiates them in nature will be constantly challenged. Here, we compare and contrast AdoMet and cobalamin (Cbl) and consider why Cbl-dependent AdoMet radical enzymes require two cofactors that are so similar in their reactivity. We further carry out structural comparisons employing the recently determined crystal structure of oxetanocin-A biosynthetic enzyme OxsB, the first three-dimensional structural data on a Cbl-dependent AdoMet radical enzyme. We find that the structural motifs responsible for housing the AdoMet radical machinery are largely conserved, whereas the motifs responsible for binding additional cofactors are much more varied.}, } @article {pmid29925254, year = {2018}, author = {Conaway, RC}, title = {Metabolic Regulation of Transcription and Chromatin.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {23-25}, doi = {10.1146/annurev-biochem-062917-012600}, pmid = {29925254}, issn = {1545-4509}, abstract = {Although cell metabolism has been established as a major regulator of eukaryotic gene expression, the mechanisms underlying this regulation are still being uncovered. Recent years have seen great advances in our understanding of biochemical mechanisms of metabolic regulation of transcription and chromatin. Prime examples include insights into how nutrients and cellular energy status regulate synthesis of ribosomal RNAs by RNA polymerases I and III during ribosome biogenesis and how a variety of enzymes that catalyze modifications of histones in chromatin are regulated by the levels of certain metabolites. This volume of the Annual Review of Biochemistry includes a set of reviews describing these and other advances in understanding aspects of the metabolic regulation of RNA polymerases I and III transcription and chromatin.}, } @article {pmid29924690, year = {2019}, author = {Gawarkiewicz, G and Malek Mercer, A}, title = {Partnering with Fishing Fleets to Monitor Ocean Conditions.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {391-411}, doi = {10.1146/annurev-marine-010318-095201}, pmid = {29924690}, issn = {1941-0611}, abstract = {Engaging ocean users, including fishing fleets, in oceanographic and ecological research is a valuable method for collecting high-quality data, improving cost efficiency, and increasing societal appreciation for scientific research. As research partners, fishing fleets provide broad access to and knowledge of the ocean, and fishers are highly motivated to use the data collected to better understand the ecosystems in which they harvest. Here, we discuss recent trends in collaborative research that have increased the capacity of and access to scientific data collection. We also describe common elements of successful collaborative research programs, including definition of a scientific problem and goals, choice of technology, data collection and sampling design, data management and dissemination, and data analysis and communication. Finally, we review four case studies that demonstrate the general principles of effective collaborative research as well as the utility of citizen-collected data for academic research and fisheries management. We also discuss the challenge of funding, particularly as it relates to maintaining collaborative research programs in the long term. We conclude with a discussion of likely future trends. Ultimately, we predict that collaborative research will continue to grow in importance as climate change increasingly impacts ocean ecosystems, commercial fisheries, and the global food supply.}, } @article {pmid29924687, year = {2018}, author = {Müller, V and Chowdhury, NP and Basen, M}, title = {Electron Bifurcation: A Long-Hidden Energy-Coupling Mechanism.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {331-353}, doi = {10.1146/annurev-micro-090816-093440}, pmid = {29924687}, issn = {1545-3251}, abstract = {A decade ago, a novel mechanism to drive thermodynamically unfavorable redox reactions was discovered that is used in prokaryotes to drive endergonic electron transfer reactions by a direct coupling to an exergonic redox reaction in one soluble enzyme complex. This process is referred to as flavin-based electron bifurcation, or FBEB. An important function of FBEB is that it allows the generation of reduced low-potential ferredoxin (Fdred) from comparably high-potential electron donors such as NADH or molecular hydrogen (H2). Fdred is then the electron donor for anaerobic respiratory chains leading to the synthesis of ATP. In many metabolic scenarios, Fd is reduced by metabolic oxidoreductases and Fdred then drives endergonic metabolic reactions such as H2 production by the reverse, electron confurcation. FBEB is energetically more economical than ATP hydrolysis or reverse electron transport as a driving force for endergonic redox reactions; thus, it does "save" cellular ATP. It is essential for autotrophic growth at the origin of life and also allows for heterotrophic growth on certain low-energy substrates.}, } @article {pmid29924686, year = {2018}, author = {Bloomfield, G}, title = {Spo11-Independent Meiosis in Social Amoebae.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {293-307}, doi = {10.1146/annurev-micro-090817-062232}, pmid = {29924686}, issn = {1545-3251}, abstract = {Sex in social amoebae (or dictyostelids) has a number of striking features. Dictyostelid zygotes do not proliferate but grow to a large size by feeding on other cells of the same species, each zygote ultimately forming a walled structure called a macrocyst. The diploid macrocyst nucleus undergoes meiosis, after which a single meiotic product survives to restart haploid vegetative growth. Meiotic recombination is generally initiated by the Spo11 enzyme, which introduces DNA double-strand breaks. Uniquely, as far as is known among sexual eukaryotes, dictyostelids lack a SPO11 gene. Despite this, recombination occurs at high frequencies during meiosis in dictyostelids, through unknown mechanisms. The molecular processes underlying these events, and the evolutionary drivers that brought them into being, may shed light on the genetic conflicts that occur within and between genomes, and how they can be resolved.}, } @article {pmid29924496, year = {2018}, author = {Rico-Guevara, A and Hurme, KJ}, title = {Intrasexually selected weapons.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12436}, pmid = {29924496}, issn = {1469-185X}, abstract = {We propose a practical concept that distinguishes the particular kind of weaponry that has evolved to be used in combat between individuals of the same species and sex, which we term intrasexually selected weapons (ISWs). We present a treatise of ISWs in nature, aiming to understand their distinction and evolution from other secondary sex traits, including from 'sexually selected weapons', and from sexually dimorphic and monomorphic weaponry. We focus on the subset of secondary sex traits that are the result of same-sex combat, defined here as ISWs, provide not previously reported evolutionary patterns, and offer hypotheses to answer questions such as: why have only some species evolved weapons to fight for the opposite sex or breeding resources? We examined traits that seem to have evolved as ISWs in the entire animal phylogeny, restricting the classification of ISW to traits that are only present or enlarged in adults of one of the sexes, and are used as weapons during intrasexual fights. Because of the absence of behavioural data and, in many cases, lack of sexually discriminated series from juveniles to adults, we exclude the fossil record from this review. We merge morphological, ontogenetic, and behavioural information, and for the first time thoroughly review the tree of life to identify separate evolution of ISWs. We found that ISWs are only found in bilateral animals, appearing independently in nematodes, various groups of arthropods, and vertebrates. Our review sets a reference point to explore other taxa that we identify with potential ISWs for which behavioural or morphological studies are warranted. We establish that most ISWs come in pairs, are located in or near the head, are endo- or exoskeletal modifications, are overdeveloped structures compared with those found in females, are modified feeding structures and/or locomotor appendages, are most common in terrestrial taxa, are frequently used to guard females, territories, or both, and are also used in signalling displays to deter rivals and/or attract females. We also found that most taxa lack ISWs, that females of only a few species possess better-developed weapons than males, that the cases of independent evolution of ISWs are not evenly distributed across the phylogeny, and that animals possessing the most developed ISWs have non-hunting habits (e.g. herbivores) or are faunivores that prey on very small prey relative to their body size (e.g. insectivores). Bringing together perspectives from studies on a variety of taxa, we conceptualize that there are five ways in which a sexually dimorphic trait, apart from the primary sex traits, can be fixed: sexual selection, fecundity selection, parental role division, differential niche occupation between the sexes, and interference competition. We discuss these trends and the factors involved in the evolution of intrasexually selected weaponry in nature.}, } @article {pmid29924345, year = {2018}, author = {Helleu, Q and Levine, MT}, title = {Recurrent Amplification of the Heterochromatin Protein 1 (HP1) Gene Family across Diptera.}, journal = {Molecular biology and evolution}, volume = {35}, number = {10}, pages = {2375-2389}, pmid = {29924345}, issn = {1537-1719}, support = {R00 GM107351/GM/NIGMS NIH HHS/United States ; R35 GM124684/GM/NIGMS NIH HHS/United States ; }, abstract = {The heterochromatic genome compartment mediates strictly conserved cellular processes such as chromosome segregation, telomere integrity, and genome stability. Paradoxically, heterochromatic DNA sequence is wildly unconserved. Recent reports that many hybrid incompatibility genes encode heterochromatin proteins, together with the observation that interspecies hybrids suffer aberrant heterochromatin-dependent processes, suggest that heterochromatic DNA packaging requires species-specific innovations. Testing this model of coevolution between fast-evolving heterochromatic DNA and its packaging proteins begins with defining the latter. Here we describe many such candidates encoded by the Heterochromatin Protein 1 (HP1) gene family across Diptera, an insect Order that encompasses dramatic episodes of heterochromatic sequence turnover. Using BLAST, synteny analysis, and phylogenetic tree building across 64 Diptera genomes, we discovered a staggering 121 HP1 duplication events. In contrast, we observed virtually no gene duplication in gene families that share a common "chromodomain" with HP1s, including Polycomb and Su(var)3-9. The remarkably high number of Dipteran HP1 paralogs arises from distant clades undergoing convergent HP1 family amplifications. These independently derived, young HP1s span diverse ages, domain structures, and rates of molecular evolution, including episodes of positive selection. Moreover, independently derived HP1s exhibit convergent expression evolution. While ancient HP1 parent genes are transcribed ubiquitously, young HP1 paralogs are transcribed primarily in male germline tissue, a pattern typical of young genes. Pervasive gene youth, rapid evolution, and germline specialization implicate heterochromatin-encoded selfish elements driving recurrent HP1 gene family expansions. The 121 young genes offer valuable experimental traction for elucidating the germline processes shaped by Diptera's many dramatic episodes of heterochromatin turnover.}, } @article {pmid29924340, year = {2018}, author = {Spielman, SJ and Kosakovsky Pond, SL}, title = {Relative evolutionary rates in proteins are largely insensitive to the substitution model.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29924340}, issn = {1537-1719}, support = {R01 GM093939/GM/NIGMS NIH HHS/United States ; U01 GM110749/GM/NIGMS NIH HHS/United States ; }, abstract = {The relative evolutionary rates at individual sites in proteins are informative measures of conservation or adaptation. Often used as evolutionarily-aware conservation scores, relative rates reveal key functional or strongly-selected residues. Estimating rates in a phylogenetic context requires specifying a protein substitution model, which is typically a phenomenological model trained on a large empirical dataset. A strong emphasis has traditionally been placed on selecting the "best-fit" model, with the implicit understanding that suboptimal or otherwise ill-fitting models might bias inferences. However, the pervasiveness and degree of such bias has not been systematically examined. We investigated how model choice impacts site-wise relative rates in a large set of empirical protein alignments. We compared models designed for use on any general protein, models designed for specific domains of life, and the simple equal-rates Jukes Cantor-style model (JC). As expected, information theoretic measures showed overwhelming evidence that some models fit the data decidedly better than others. By contrast, estimates of site-specific evolutionary rates were impressively insensitive to the substitution model used, revealing an unexpected degree of robustness to potential model misspecification. A deeper examination of the fewer than 5% of sites for which model inferences differed in a meaningful way showed that the JC model could uniquely identify rapidly-evolving sites that models with empirically-derived exchangeabilities failed to detect. We conclude that relative protein rates appear robust to the applied substitution model, and any sensible model of protein evolution, regardless of its fit to the data, should produce broadly consistent evolutionary rates.}, } @article {pmid29924339, year = {2018}, author = {Piekarski, PK and Carpenter, JM and Lemmon, AR and Moriarty Lemmon, E and Sharanowski, BJ}, title = {Phylogenomic evidence overturns current conceptions of social evolution in wasps (Vespidae).}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29924339}, issn = {1537-1719}, abstract = {The hypothesis that eusociality originated once in Vespidae has shaped interpretation of social evolution for decades and has driven the supposition that preimaginal morphophysiological differences between castes were absent at the outset of eusociality. Many researchers also consider casteless nest-sharing an antecedent to eusociality. Together, these ideas endorse a stepwise progression of social evolution in wasps (solitary → casteless nest-sharing → eusociality with rudimentary behavioral castes → eusociality with preimaginal caste-biasing → morphologically differentiated castes). Here we infer the phylogeny of Vespidae using sequence data generated via anchored hybrid enrichment from 378 loci across 136 vespid species and perform ancestral state reconstructions to test whether rudimentary and monomorphic castes characterized the initial stages of eusocial evolution. Our results reject the single origin of eusociality hypothesis, contest the supposition that eusociality emerged from a casteless nest-sharing ancestor, and suggest that eusociality in Polistinae + Vespinae began with castes having morphological differences. An abrupt appearance of castes with ontogenetically established morphophysiological differences conflicts with the current conception of stepwise social evolution and suggests that the climb up the ladder of sociality does not occur through sequential mutation. Phenotypic plasticity and standing genetic variation could explain how cooperative brood care evolved in concert with nest-sharing and how morphologically dissimilar castes arose without a rudimentary intermediate. Furthermore, preimaginal caste-biasing at the outset of eusociality implicates a subsocial route to eusociality in Polistinae + Vespinae, emphasizing the role of mother-daughter interactions and subfertility (i.e. the cost component of kin selection) in the origin of workers.}, } @article {pmid29924338, year = {2018}, author = {Gong, Z and Han, GZ}, title = {Insect retroelements provide novel insights into the origin of hepatitis B viruses.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy129}, pmid = {29924338}, issn = {1537-1719}, abstract = {The origin of hepadnaviruses (Hepadnaviridae), a group of reverse-transcribing DNA viruses that infect vertebrates, remains mysterious. All the known retrotransposons are only distantly related to hepadnaviruses. Here we report the discovery of two novel lineages of retroelements, which we designate hepadnavirus-like retroelement (HEART1 and HEART2), within the insect genomes through screening 1,095 eukaryotic genomes. Both phylogenetic and similarity analyses suggest that the HEART retroelements represent the closest non-viral relatives of hepadnaviruses so far. The discovery of HEART retroelements narrows down the evolutionary gap between hepadnaviruses and retrotransposons and might thus provide unique insights into the origin and evolution of hepadnaviruses.}, } @article {pmid29924337, year = {2018}, author = {Ponce-Toledo, RI and Moreira, D and López-García, P and Deschamps, P}, title = {Secondary Plastids of Euglenids and Chlorarachniophytes Function with a Mix of Genes of Red and Green Algal Ancestry.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy121}, pmid = {29924337}, issn = {1537-1719}, abstract = {Endosymbiosis has been common all along eukaryotic evolution, providing opportunities for genomic and organellar innovation. Plastids are a prominent example. After the primary endosymbiosis of the cyanobacterial plastid ancestor, photosynthesis spread in many eukaryotic lineages via secondary endosymbioses involving red or green algal endosymbionts and diverse heterotrophic hosts. However, the number of secondary endosymbioses and how they occurred remain poorly understood. In particular, contrasting patterns of endosymbiotic gene transfer (EGT) have been detected and subjected to various interpretations. In this context, accurate detection of EGTs is essential to avoid wrong evolutionary conclusions. We have assembled a strictly selected set of markers that provides robust phylogenomic evidence suggesting that nuclear genes involved in the function and maintenance of green secondary plastids in chlorarachniophytes and euglenids have unexpected mixed red and green algal origins. This mixed ancestry contrasts with the clear red algal origin of most nuclear genes carrying similar functions in secondary algae with red plastids.}, } @article {pmid29924328, year = {2018}, author = {Leite, DJ and Baudouin-Gonzalez, L and Iwasaki-Yokozawa, S and Lozano-Fernandez, J and Turetzek, N and Akiyama-Oda, Y and Prpic, NM and Pisani, D and Oda, H and Sharma, PP and McGregor, AP}, title = {Homeobox gene duplication and divergence in arachnids.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29924328}, issn = {1537-1719}, abstract = {Homeobox genes are key toolkit genes that regulate the development of metazoans and changes in their regulation and copy number have contributed to the evolution of phenotypic diversity. We recently identified a whole genome duplication (WGD) event that occurred in an ancestor of spiders and scorpions (Arachnopulmonata), and that many homeobox genes, including two Hox clusters, appear to have been retained in arachnopulmonates. To better understand the consequences of this ancient WGD and the evolution of arachnid homeobox genes, we have characterised and compared the homeobox repertoires in a range of arachnids. We found that many families and clusters of these genes are duplicated in all studied arachnopulmonates (Parasteatoda tepidariorum, Pholcus phalangioides, Centruroides sculpturatus and Mesobuthus martensii) compared with non-arachnopumonate arachnids (Phalangium opilio, Neobisium carcinoides, Hesperochernes sp. and Ixodes scapularis). To assess divergence in the roles of homeobox ohnologs, we analysed the expression of P. tepidariorum homeobox genes during embryogenesis and found pervasive changes in the level and timing of their expression. Furthermore, we compared the spatial expression of a subset of P. tepidariorum ohnologs with their single copy orthologs in P. opilio embryos. We found evidence for likely subfunctionlisation and neofunctionalisation of these genes in the spider. Overall our results show a high level of retention of homeobox genes in spiders and scorpions post WGD, which is likely to have made a major contribution to their developmental evolution and diversification through pervasive subfunctionlisation and neofunctionalisation, and paralleling the outcome of WGD in vertebrates.}, } @article {pmid29923825, year = {2018}, author = {Christensen, H and Bisgaard, M}, title = {Classification of genera of Pasteurellaceae using conserved predicted protein sequences.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2692-2696}, doi = {10.1099/ijsem.0.002860}, pmid = {29923825}, issn = {1466-5034}, mesh = {Actinobacillus/classification ; Amino Acid Sequence ; Bacterial Typing Techniques ; Base Composition ; Base Sequence ; DNA, Bacterial/genetics ; Haemophilus/classification ; Pasteurella/classification ; Pasteurellaceae/*classification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The aim of the investigation was to investigate the phylogeny of the 49 type strains of species of Pasteurellaceae and three genomospecies, which are available with whole genomic sequences. The genomes were downloaded from National Center for Biotechnological Information and for three species of Avibacterium sequenced in the present investigation. From the predicted protein sequences of proteins, which were conserved in all genomes, 31 proteins were randomly selected for the study. The protein sequences were concatenated for each taxon, and a multiple alignment reconstructed for the 52 taxa. Phylogenetic analysis was performed by using the maximum-likelihood and neighbour-joining methods and confirmed the classification of the genera, which have been classified based on phylogenetic analysis of 16S rRNA gene sequences. The comparison linked [Haemophilus]parainfluezae and [Haemophilus] pittmania with Haemophilus influenzae (type species of genus) although at a much lower level than observed for Haemophilus aegyptius, H. influenzae and Haemophilus haemolyticus. The comparison documented that three, three and nine species of Actinobacillus, Pasteurella and Haemophilus, respectively, are not properly classified at genus level. Similar conclusions have been drawn by 16S rRNA gene sequence comparisons. The highest inter genus pairwise similarity was 88 % based on the comparison of the 31 concatenated protein sequences of the species included in the comparison. The level of intra genus pairwise similarity was also 88 %.}, } @article {pmid29923818, year = {2018}, author = {Zhang, TY and Yu, Y and Zhang, MY and Cheng, J and Chen, ZJ and Zhang, JY and Zhang, YX}, title = {Verruconis panacis sp. nov., an endophyte isolated from Panax notoginseng.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2499-2503}, doi = {10.1099/ijsem.0.002862}, pmid = {29923818}, issn = {1466-5034}, mesh = {Ascomycota/*classification/genetics/isolation & purification ; China ; DNA, Fungal/genetics ; Endophytes/isolation & purification ; Mycological Typing Techniques ; Panax notoginseng/*microbiology ; *Phylogeny ; Plant Roots/microbiology ; Sequence Analysis, DNA ; }, abstract = {An endophytic strain (designated as strain SYPF 8337T) was isolated from the root of 3-year-old Panax notoginseng in Yunnan province of China. Strain SYPF 8337T grew slowly and formed pale brown to brown colonies. Phylogenetic analyses indicated that strain SYPF 8337T was placed in the Verruconis clade. Different from other Verruconis species, strain SYPF 8337T produced four-cell conidia. Furthermore, strain SYPF 8337T is the first fungus isolated as an endophyte of P. notoginseng in the genus Verruconis. Combined with the morphology and molecular analyses, a new species named Verruconis panacis sp. nov. is proposed.}, } @article {pmid29923816, year = {2018}, author = {Hwang, WM and Ko, Y and Kim, JH and Kang, K}, title = {Ahniella affigens gen. nov., sp. nov., a gammaproteobacterium isolated from sandy soil near a stream.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2478-2484}, doi = {10.1099/ijsem.0.002859}, pmid = {29923816}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; *Rivers ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A bacterial strain, designated D13T, was isolated from sandy soil near a stream in Sinan-gun, Republic of Korea. Cells were Gram-stain-negative, aerobic, non-motile and flexible rod-shaped. Growth occurred at 15-35 °C (optimum 30 °C) and pH 6.5-8.0 (pH 7.0). NaCl was not obligatory for growth but could be tolerated at up to 0.5 % (w/v) NaCl. The DNA G+C content of the genomic DNA of strain D13T was 57.7 mol% and a phylogenetic analysis of the 16S rRNA gene sequence revealed that strain D13T formed a distinct evolutionary lineage within the family Rhodanobacteraceae of the order Lysobacterales. Strain D13T showed highest 16S rRNA sequence similarity to Lysobacter hankyongensis KTCe-2T (92.7 %), followed by Luteimonas cucumeris Y4T (92.7 %), Dyella japonica XD53T (92.6 %) and Aquimonas voraii GPTSA 20T (92.5 %). The major cellular fatty acids (>10 % of the total) were iso-C16 : 0, iso-C15 : 0 and summed feature 9 (iso-C17 : 1ω9с and/or C16 : 0 10-methyl). The respiratory quinone was ubiquinone-8 and the major polar lipids of the isolate consisted of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylmonomethylethanolamine. Based on polyphasic analysis, strain D13T could be differentiated from other genera in the family Rhodanobacteraceae, which suggests that strain D13T represents a novel species of a new genus in the family Rhodanobacteraceae, for which the name Ahniella affigens gen. nov., sp. nov. is proposed. The type strain is D13T (=KACC 19270T=JCM 31634T).}, } @article {pmid29923657, year = {2018}, author = {Delmas, E and Besson, M and Brice, MH and Burkle, LA and Dalla Riva, GV and Fortin, MJ and Gravel, D and Guimarães, PR and Hembry, DH and Newman, EA and Olesen, JM and Pires, MM and Yeakel, JD and Poisot, T}, title = {Analysing ecological networks of species interactions.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12433}, pmid = {29923657}, issn = {1469-185X}, abstract = {Network approaches to ecological questions have been increasingly used, particularly in recent decades. The abstraction of ecological systems - such as communities - through networks of interactions between their components indeed provides a way to summarize this information with single objects. The methodological framework derived from graph theory also provides numerous approaches and measures to analyze these objects and can offer new perspectives on established ecological theories as well as tools to address new challenges. However, prior to using these methods to test ecological hypotheses, it is necessary that we understand, adapt, and use them in ways that both allow us to deliver their full potential and account for their limitations. Here, we attempt to increase the accessibility of network approaches by providing a review of the tools that have been developed so far, with - what we believe to be - their appropriate uses and potential limitations. This is not an exhaustive review of all methods and metrics, but rather, an overview of tools that are robust, informative, and ecologically sound. After providing a brief presentation of species interaction networks and how to build them in order to summarize ecological information of different types, we then classify methods and metrics by the types of ecological questions that they can be used to answer from global to local scales, including methods for hypothesis testing and future perspectives. Specifically, we show how the organization of species interactions in a community yields different network structures (e.g., more or less dense, modular or nested), how different measures can be used to describe and quantify these emerging structures, and how to compare communities based on these differences in structures. Within networks, we illustrate metrics that can be used to describe and compare the functional and dynamic roles of species based on their position in the network and the organization of their interactions as well as associated new methods to test the significance of these results. Lastly, we describe potential fruitful avenues for new methodological developments to address novel ecological questions.}, } @article {pmid29923246, year = {2018}, author = {Saunders, PA and Neuenschwander, S and Perrin, N}, title = {Sex chromosome turnovers and genetic drift: a simulation study.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1413-1419}, doi = {10.1111/jeb.13336}, pmid = {29923246}, issn = {1420-9101}, support = {31003A_166323//Swiss National Science Foundation/ ; }, abstract = {The recent advances of new genomic technologies have enabled the identification and characterization of sex chromosomes in an increasing number of nonmodel species, revealing that many plants and animals undergo frequent sex chromosome turnovers. What evolutionary forces drive these turnovers remains poorly understood, but it was recently proposed that drift might play a more important role than generally assumed. We analysed the dynamics of different types of turnovers using individual-based simulations and show that when mediated by genetic drift, turnovers are usually easier to achieve than substitutions at neutral markers, but that their dynamics and relative likelihoods vary with the type of the resident and emergent sex chromosome system (XY and/or ZW) and the dominance relationships among the sex-determining factors. Focusing on turnovers driven by epistatically dominant mutations, we find that drift-mediated turnovers that preserve the heterogamety pattern are 2-4× more likely than those along which the heterogametic sex changes. This ratio nevertheless decreases along with effective population size and can even reverse in case of extreme polygyny. This can be attributed to a 'drift-induced' selective force, known to influence transitions between male and female heterogamety, but which according to our study does not affect turnovers that preserve the heterogametic sex.}, } @article {pmid29922971, year = {2018}, author = {Yin, S and Zhu, H and Shen, M and Li, G and Lu, S and Zhao, Y and Le, S and Tan, Y and Peng, Y and Hu, F and Wang, J}, title = {Surface Display of Heterologous β-Galactosidase in Food-Grade Recombinant Lactococcus lactis.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29922971}, issn = {1432-0991}, support = {31201341//National Natural Science Foundation of China/ ; 2010XQN06//Third Military Medical University Youth Science Foundation/ ; }, abstract = {β-Galactosidase is an essential enzyme for the metabolism of lactose in human beings and has an important role in the treatment of lactose intolerance (LI). β-Galactosidase expressed by intestinal microflora, such as lactic acid bacteria (LAB), also alleviates LI. A promising approach to LI management is to exploit a food-grade LAB delivery system that can inhabit the human intestine and overproduce β-galactosidase. In this study, we constructed a food-grade β-galactosidase surface display delivery system and then integrated into the chromosome of Lactococcus lactis (L. lactis) NZ9000 using recombination. Western blot and immunofluorescence analyses confirmed that β-galactosidase was expressed on the cell surface of recombinant L. lactis stain NZ-SDL. The whole-cell biocatalyst exhibits Vmax and Km values of 121.38 ± 7.17 UONPG/g and 65.36 ± 5.54 mM, based on ONPG hydrolysis. The optimum temperature for enzyme activity is 37 °C and the optimum pH is 5.0. Activity of the whole-cell biocatalyst is promoted by Mg2+, Ca2+, and K+, but inhibited by Zn2+, Fe2+, and Fe3+. The system has a thermal stability similar to purified β-galactosidase but better pH stability, and is also more stable in artificial intestinal juice. Oral administration and intraperitoneal injections of NZ-SDL in mice cause no detectable health effects. In conclusion, we have successfully constructed a food-grade gene expression system in L. lactis that displays β-galactosidase on the cell surface. This system exhibits good enzyme activity and stability in vitro, and is safe in vivo. It is therefore a promising candidate for use in LI management.}, } @article {pmid29922970, year = {2018}, author = {Li, J and Li, L and Jiang, H and Yuan, L and Zhang, L and Ma, JE and Zhang, X and Cheng, M and Chen, J}, title = {Fecal Bacteriome and Mycobiome in Bats with Diverse Diets in South China.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29922970}, issn = {1432-0991}, support = {2016B070701016//PlanningFunds of Science and Technology of Guangdong Province/ ; 2013B031500006//PlanningFunds of Science and Technology of Guangdong Province/ ; 2016GDASPT-0107//Funds for Environment Construction and Capacity Building of GDAS' Research Platform/ ; 2017GDASCX-0107//GDAS Special Project of Science and Technology Development/ ; }, abstract = {Bats can be divided into frugivory, nectarivory, insectivory, and sanguivory based on their diets, and are therefore ideal wild animal models to study the relationship between diets and intestinal microflora. Early studies of bat gut bacteria showed that the diversity and structure of intestinal bacterial communities in bats are closely related to dietary changes. Worthy of note, intestinal microbes are composed of bacteria, fungi, protozoa, and archaea. Although the number of gut fungi is much lower than that of gut bacteria, they also play an important role in maintaining the host homeostasis. However, there are still few reports on the relationship between the gut mycobiota and the dietary habits of the host. In addition, bats have also been shown to naturally transmit pathogenic viruses and bacteria through their feces and saliva, but fungal infections from bat are less studied. Here, we used high-throughput sequencing of bacterial 16S and eukaryotic 18S rRNA genes in the V4 and V9 regions to characterize fecal bacterial and fungal microbiota in phytophagous and insectivorous bats in South China. The results show that the gut microbiota in bats were dominated by bacterial phyla Proteobacteria, Firmicutes, Tenericutes and Bacteroidetes, and fungal phyla Ascomycota and Basidiomycota. There was a significant difference in the diversity of bacterial and fungal microbiota between the groups, in addition to specific bacteria and fungi populations on each of them. Of note, the number of fungi in the feces of herbivorous bats is relatively higher. Most of these fungi are foodborne and are also pathogens of humans and other animals. Thus, bats are natural carriers of fungal pathogens. The current study expands the understanding of the bat gut bacterial and fungal mycobiota and provides further insight into the transmission of fungal pathogens.}, } @article {pmid29922969, year = {2018}, author = {Wang, J and Xu, J and Luo, S and Ma, Z and Bechthold, A and Yu, X}, title = {AdpA sd , a Positive Regulator for Morphological Development and Toyocamycin Biosynthesis in Streptomyces diastatochromogenes 1628.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29922969}, issn = {1432-0991}, abstract = {AdpA is studied and considered as a pleiotropic regulator which is involved in morphological development and secondary metabolism in many Streptomyces. In this study, AdpAsd, which was cloned from toyocamycin (TM)-producing strain Streptomyces diastatochromogenes 1628, was identified as an ortholog of AdpA and belongs to a large subfamily of the AraC/XylS family. In order to elucidate the correlation of AdpAsd with TM biosynthesis and morphological differentiation, adpA sd was placed under the control of the ermE* promoter in plasmid pIB139. By intergeneric conjugation, the resulting plasmid pIB139-adpA sd was introduced into mutant S. diastatochromogenes 1628-T62 that is defective in sporulation and had limited TM production as well as transcriptional level of gene adpA sd , yielding the recombinant strain S. diastatochromogenes 1628-T62A. As expected, due to over-expression of adpA sd , the S. diastatochromogenes 1628-T62A restored spore formation to a certain extent compared with control strain S. diastatochromogenes 1628-T62. Moreover, compared with control strain 1628-T62, the TM production of recombinant 1628-T62A was increased by 120.1% on 5 l fermenter. In addition, by using semi-quantitative reverse transcription-PCR analysis, we discovered that the transcriptional levels of gene adpA sd and the all toy genes involved in TM biosynthesis were elevated in recombinant 1628-T62A compared with S. diastatochromogenes 1628-T62. These results confirm that cloned adpA sd plays a positive role in TM biosynthesis and morphological differentiation.}, } @article {pmid29921983, year = {2018}, author = {Cohen, JI}, title = {Author Correction: New activities for old antibiotics.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {844}, doi = {10.1038/s41564-018-0185-8}, pmid = {29921983}, issn = {2058-5276}, abstract = {In the version of this News and Views originally published, the author made an incorrect reference to 'mice deficient in Mx1'. This has now been corrected so that the text instead refers to 'mice congenic for Mx1'. The full corrected sentence reads as "Pretreatment of mice congenic for Mx1, an ISG that is critical for protection of animals from influenza, with intranasal neomycin significantly improved survival; however, about 50% of the mice died."}, } @article {pmid29921925, year = {2018}, author = {Fernández, ÁF and Sebti, S and Wei, Y and Zou, Z and Shi, M and McMillan, KL and He, C and Ting, T and Liu, Y and Chiang, WC and Marciano, DK and Schiattarella, GG and Bhagat, G and Moe, OW and Hu, MC and Levine, B}, title = {Author Correction: Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.}, journal = {Nature}, volume = {561}, number = {7723}, pages = {E30}, doi = {10.1038/s41586-018-0270-4}, pmid = {29921925}, issn = {1476-4687}, abstract = {In this Letter, the graphs in Fig. 2a and c were inadvertently the same owing to a copy and paste error from the original graphs in Prism. The Source Data files containing the raw data were correct. Fig. 2c has been corrected online.}, } @article {pmid29921914, year = {2018}, author = {Abbink, P and Stephenson, KE and Barouch, DH}, title = {Zika virus vaccines.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {594-600}, pmid = {29921914}, issn = {1740-1534}, support = {UM1 AI124377/AI/NIAID NIH HHS/United States ; UM1 AI126603/AI/NIAID NIH HHS/United States ; }, abstract = {The recent epidemic of Zika virus (ZIKV) in the Americas has revealed the devastating consequences of ZIKV infection, particularly in pregnant women. Congenital Zika syndrome, characterized by malformations and microcephaly in neonates as well as developmental challenges in children, highlights the need for the development of a safe and effective vaccine. Multiple vaccine candidates have been developed and have shown promising results in both animal models and phase I clinical trials. However, important challenges remain for the clinical development of these vaccines. In this Progress article, we discuss recent preclinical studies and lessons learned from first-in-human clinical trials with ZIKV vaccines.}, } @article {pmid29921867, year = {2018}, author = {Furlong, R}, title = {Refining the splice region.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {470-471}, doi = {10.1038/s41576-018-0028-8}, pmid = {29921867}, issn = {1471-0064}, } @article {pmid29921860, year = {2018}, author = {}, title = {Curbing opioid addiction needs more than new drugs.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {343}, doi = {10.1038/d41586-018-05466-6}, pmid = {29921860}, issn = {1476-4687}, mesh = {*Analgesics, Opioid ; Behavior, Addictive ; Humans ; *Opioid-Related Disorders ; Research Design ; }, } @article {pmid29921859, year = {2018}, author = {Willyard, C}, title = {New human gene tally reignites debate.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {354-355}, doi = {10.1038/d41586-018-05462-w}, pmid = {29921859}, issn = {1476-4687}, mesh = {Disease/genetics ; *Dissent and Disputes ; *Genes ; *Human Genome Project ; Humans ; Mutation ; *Uncertainty ; }, } @article {pmid29921858, year = {2018}, author = {Borsa, P and Richer de Forges, B and Baudat-Franceschi, J}, title = {Keep cruises off remote reef rich in fish and birds.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {372}, doi = {10.1038/d41586-018-05453-x}, pmid = {29921858}, issn = {1476-4687}, mesh = {Animals ; *Anthozoa ; Birds ; Coral Reefs ; Ecosystem ; Fishes ; *Nitrogen ; }, } @article {pmid29921857, year = {2018}, author = {Tregoning, J}, title = {How will you judge me if not by impact factor?.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {345}, doi = {10.1038/d41586-018-05467-5}, pmid = {29921857}, issn = {1476-4687}, mesh = {*Efficiency ; Job Application ; *Journal Impact Factor ; *Judgment ; Occupational Stress ; Peer Review, Research/*methods ; Research Personnel/psychology/*standards ; Reward ; Social Media/statistics & numerical data ; *Uncertainty ; }, } @article {pmid29921856, year = {2018}, author = {Meadows, A}, title = {DOIs and other persistent identifiers have much more to offer science.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {372}, doi = {10.1038/d41586-018-05456-8}, pmid = {29921856}, issn = {1476-4687}, mesh = {*Authorship ; Automation ; Bibliometrics ; *Information Systems ; *Peer Review, Research ; *Periodicals as Topic ; Research Personnel/*statistics & numerical data ; Research Report ; }, } @article {pmid29921855, year = {2018}, author = {Peels, R and Bouter, L}, title = {Humanities need a replication drive too.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {372}, doi = {10.1038/d41586-018-05454-w}, pmid = {29921855}, issn = {1476-4687}, mesh = {Anthropology/standards ; Archaeology/standards ; *Humanities ; Linguistics/standards ; Paintings ; Reproducibility of Results ; }, } @article {pmid29921854, year = {2018}, author = {Filella, M and Dror, I and Rauch, S}, title = {Risk assessment of tech metals is ongoing.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {372}, doi = {10.1038/d41586-018-05455-9}, pmid = {29921854}, issn = {1476-4687}, mesh = {Environmental Monitoring ; Metals ; *Risk Assessment ; *Technology ; }, } @article {pmid29921853, year = {2018}, author = {Ledford, H}, title = {Cancer researchers target the dormant cells that seed tumours.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {355-356}, doi = {10.1038/d41586-018-05445-x}, pmid = {29921853}, issn = {1476-4687}, mesh = {Humans ; *Neoplasm Seeding ; *Neoplasms ; }, } @article {pmid29921852, year = {2018}, author = {Silver, A}, title = {Microsoft's purchase of GitHub leaves some scientists uneasy.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {353}, doi = {10.1038/d41586-018-05426-0}, pmid = {29921852}, issn = {1476-4687}, mesh = {Cooperative Behavior ; Datasets as Topic ; Humans ; Industry/*economics ; *Information Dissemination ; Internet ; *Open Access Publishing/trends ; Research Personnel/*psychology ; Software/*economics ; }, } @article {pmid29921851, year = {2018}, author = {Schiermeier, Q}, title = {World Cup ban on radioactive chemicals frustrates Russian biochemistry labs.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {351-352}, doi = {10.1038/d41586-018-05423-3}, pmid = {29921851}, issn = {1476-4687}, mesh = {*Biochemistry ; Hazardous Substances/*economics/*supply & distribution ; *Laboratories ; Molecular Biology ; Radioisotopes/*economics/*supply & distribution ; Russia ; Security Measures/*legislation & jurisprudence ; *Soccer ; Time Factors ; Workflow ; }, } @article {pmid29921850, year = {2018}, author = {Witze, A}, title = {Sexual harassment is rife in the sciences, finds landmark US study.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {352-353}, doi = {10.1038/d41586-018-05404-6}, pmid = {29921850}, issn = {1476-4687}, mesh = {*Behavioral Research ; Faculty/statistics & numerical data ; Female ; Humans ; Leadership ; Male ; Minority Groups/statistics & numerical data ; Sex Factors ; Sexual Harassment/legislation & jurisprudence/*prevention & control/*statistics & numerical data ; Students/statistics & numerical data ; United States ; Universities ; Vulnerable Populations/statistics & numerical data ; }, } @article {pmid29921726, year = {2018}, author = {Granter, SR and Papke, DJ}, title = {Opinion: Medical misinformation in the era of Google: Computational approaches to a pervasive problem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6318-6321}, pmid = {29921726}, issn = {1091-6490}, mesh = {Communication ; Data Accuracy ; Humans ; Internet ; Medical Informatics/*trends ; Search Engine/statistics & numerical data/trends ; }, } @article {pmid29921703, year = {2018}, author = {Garcia, D and Mitike Kassa, Y and Cuevas, A and Cebrian, M and Moro, E and Rahwan, I and Cuevas, R}, title = {Analyzing gender inequality through large-scale Facebook advertising data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6958-6963}, pmid = {29921703}, issn = {1091-6490}, mesh = {Female ; Humans ; *Interpersonal Relations ; Male ; *Models, Theoretical ; *Sexism ; *Social Media ; }, abstract = {Online social media are information resources that can have a transformative power in society. While the Web was envisioned as an equalizing force that allows everyone to access information, the digital divide prevents large amounts of people from being present online. Online social media, in particular, are prone to gender inequality, an important issue given the link between social media use and employment. Understanding gender inequality in social media is a challenging task due to the necessity of data sources that can provide large-scale measurements across multiple countries. Here, we show how the Facebook Gender Divide (FGD), a metric based on aggregated statistics of more than 1.4 billion users in 217 countries, explains various aspects of worldwide gender inequality. Our analysis shows that the FGD encodes gender equality indices in education, health, and economic opportunity. We find gender differences in network externalities that suggest that using social media has an added value for women. Furthermore, we find that low values of the FGD are associated with increases in economic gender equality. Our results suggest that online social networks, while suffering evident gender imbalance, may lower the barriers that women have to access to informational resources and help to narrow the economic gender gap.}, } @article {pmid29921499, year = {2018}, author = {Robertson, LJ and Torgerson, PR and van der Giessen, J}, title = {Foodborne Parasitic Diseases in Europe: Social Cost-Benefit Analyses of Interventions.}, journal = {Trends in parasitology}, volume = {34}, number = {11}, pages = {919-923}, doi = {10.1016/j.pt.2018.05.007}, pmid = {29921499}, issn = {1471-5007}, abstract = {Social cost-benefit analysis (SCBA) can be used to evaluate the benefit to society as a whole of a particular intervention. Describing preliminary steps of an SCBA for two foodborne parasitic diseases, echinococcosis and cryptosporidiosis, indicates where data are needed in order to identify those interventions of greatest benefit.}, } @article {pmid29921330, year = {2018}, author = {Lawrence, SD and Novak, NG}, title = {The remarkable plethora of infestation-responsive Q-type C2H2 transcription factors in potato.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {398}, pmid = {29921330}, issn = {1756-0500}, support = {8042-22000-288-00-D//Agricultural Research Service/ ; }, mesh = {Animals ; CYS2-HIS2 Zinc Fingers/*genetics ; Gene Expression/*genetics ; Genome, Plant/*genetics ; Manduca ; Plant Proteins/*genetics ; Solanum tuberosum/*genetics/*parasitology ; }, abstract = {OBJECTIVE: Q-type C2H2 transcription factors (TF) play crucial roles in the plant response to stress, often leading to regulation of downstream genes required for tolerance to these challenges. An infestation-responsive Q-type C2H2 TF (StZFP2) is induced by wounding and infestation in potato. While mining the Solanum tuberosum Group Phureja genome for additional members of this family of proteins, five StZFP2-like genes were found on a portion of chromosome 11. The objective of this work was to differentiate these genes in tissue specificity and expression upon infestation.

RESULTS: Examination of different tissues showed that young roots had the highest amounts of transcripts for five of the genes. Expression of their transcripts upon excision or infestation by Manduca sexta, showed that all six genes were induced. Overall, each gene showed variations in its response to infestation and specificity for tissue expression. The six genes encode very similar proteins but most likely play unique roles in the plant response to infestation. In contrast, only two homologs have been identified in Arabidopsis and tomato. Overexpression of similar genes has led to enhanced tolerance to, for example, salinity, drought and pathogen stress. Discovery of these new StZFP2 homologs could provide additional resources for potato breeders.}, } @article {pmid29921329, year = {2018}, author = {Call, L and Stoll, B and Oosterloo, B and Ajami, N and Sheikh, F and Wittke, A and Waworuntu, R and Berg, B and Petrosino, J and Olutoye, O and Burrin, D}, title = {Metabolomic signatures distinguish the impact of formula carbohydrates on disease outcome in a preterm piglet model of NEC.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {111}, pmid = {29921329}, issn = {2049-2618}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; T15 LM007093/LM/NLM NIH HHS/United States ; T32 GM088129/GM/NIGMS NIH HHS/United States ; }, mesh = {Animal Feed/analysis ; Animals ; Bacillus/classification/genetics/*isolation & purification ; Clostridium/classification/genetics/*isolation & purification ; *Dietary Carbohydrates ; *Enteral Nutrition ; Enterocolitis, Necrotizing/etiology/microbiology ; Female ; Gammaproteobacteria/classification/genetics/*isolation & purification ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; High Fructose Corn Syrup/*administration & dosage ; Lactose/*administration & dosage ; Pregnancy ; Premature Birth ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Swine ; }, abstract = {BACKGROUND: Major risk factors for necrotizing enterocolitis (NEC) include premature birth and formula feeding in the context of microbial colonization of the gastrointestinal tract. We previously showed that feeding formula composed of lactose vs. corn syrup solids protects against NEC in preterm pigs; however, the microbial and metabolic effects of these different carbohydrates used in infant formula has not been explored.

OBJECTIVE: Our objective was to characterize the effects of lactose- and corn syrup solid-based formulas on the metabolic and microbial profiles of preterm piglets and to determine whether unique metabolomic or microbiome signatures correlate with severity or incidence of NEC.

DESIGN/METHODS: Preterm piglets (103 days gestation) were given total parenteral nutrition (2 days) followed by gradual (5 days) advancement of enteral feeding of formulas matched in nutrient content but containing either lactose (LAC), corn syrup solids (CSS), or 1:1 mix (MIX). Gut contents and mucosal samples were collected and analyzed for microbial profiles by sequencing the V4 region of the 16S rRNA gene. Metabolomic profiles of cecal contents and plasma were analyzed by LC/GC mass spectrometry.

RESULTS: NEC incidence was 14, 50, and 44% in the LAC, MIX, and CSS groups, respectively. The dominant classes of bacteria were Bacilli, Clostridia, and Gammaproteobacteria. The number of observed OTUs was lowest in colon contents of CSS-fed pigs. CSS-based formula was associated with higher Bacilli and lower Clostridium from clusters XIVa and XI in the colon. NEC was associated with decreased Gammaproteobacteria in the stomach and increased Clostridium sensu stricto in the ileum. Plasma from NEC piglets was enriched with metabolites of purine metabolism, aromatic amino acid metabolism, and bile acids. Markers of glycolysis, e.g., lactate, were increased in the cecal contents of CSS-fed pigs and in plasma of pigs which developed NEC.

CONCLUSIONS: Feeding formula containing lactose is not completely protective against NEC, yet selects for greater microbial richness associated with changes in Bacilli and Clostridium and lower NEC incidence. We conclude that feeding preterm piglets a corn syrup solid vs. lactose-based formula increases the incidence of NEC and produces distinct metabolomic signatures despite modest changes in microbiome profiles.}, } @article {pmid29921326, year = {2018}, author = {Tkacz, A and Hortala, M and Poole, PS}, title = {Absolute quantitation of microbiota abundance in environmental samples.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {110}, pmid = {29921326}, issn = {2049-2618}, support = {BB/N013387/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Archaea/classification/genetics/*isolation & purification ; Bacteria/classification/genetics/*isolation & purification ; *Biodiversity ; DNA, Archaeal/genetics ; DNA, Bacterial/genetics ; DNA, Fungal/genetics ; Fungi/classification/genetics/*isolation & purification ; Genes, Essential/genetics ; Microbiota/*genetics ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/genetics ; *Soil Microbiology ; }, abstract = {BACKGROUND: Microbial communities (microbiota) influence human and animal disease and immunity, geochemical nutrient cycling and plant productivity. Specific groups, including bacteria, archaea, eukaryotes or fungi, are amplified by PCR to assess the relative abundance of sub-groups (e.g. genera). However, neither the absolute abundance of sub-groups is revealed, nor can different amplicon families (i.e. OTUs derived from a specific pair of PCR primers such as bacterial 16S, eukaryotic 18S or fungi ITS) be compared. This prevents determination of the absolute abundance of a particular group and domain-level shifts in microbiota abundance can remain undetected.

RESULTS: We have developed absolute quantitation of amplicon families using synthetic chimeric DNA spikes. Synthetic spikes were added directly to environmental samples, co-isolated and PCR-amplified, allowing calculation of the absolute abundance of amplicon families (e.g. prokaryotic 16S, eukaryotic 18S and fungal ITS per unit mass of sample).

CONCLUSIONS: Spikes can be adapted to any amplicon-specific group including rhizobia from soils, Firmicutes and Bifidobacteria from human gut or Enterobacteriaceae from food samples. Crucially, using highly complex soil samples, we show that the absolute abundance of specific groups can remain steady or increase, even when their relative abundance decreases. Thus, without absolute quantitation, the underlying pathology, physiology and ecology of microbial groups may be masked by their relative abundance.}, } @article {pmid29921324, year = {2018}, author = {Jørgensen, TE and Karlsen, BO and Emblem, Å and Breines, R and Andreassen, M and Rounge, TB and Nederbragt, AJ and Jakobsen, KS and Nymark, M and Ursvik, A and Coucheron, DH and Jakt, LM and Nordeide, JT and Moum, T and Johansen, SD}, title = {Mitochondrial genome variation of Atlantic cod.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {397}, pmid = {29921324}, issn = {1756-0500}, mesh = {Animals ; DNA, Mitochondrial/*genetics ; Gadus morhua/*genetics ; Genome ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; }, abstract = {OBJECTIVE: The objective of this study was to analyse intraspecific sequence variation of Atlantic cod mitochondrial DNA, based on a comprehensive collection of completely sequenced mitochondrial genomes.

RESULTS: We determined the complete mitochondrial DNA sequence of 124 cod specimens from the eastern and western part of the species' distribution range in the North Atlantic Ocean. All specimens harboured a unique mitochondrial DNA haplotype. Nine hundred and fifty-two polymorphic sites were identified, including 109 non-synonymous sites within protein coding regions. Eighteen variable sites were identified as indels, exclusively distributed in structural RNA genes and non-coding regions. Phylogeographic analyses based on 156 available cod mitochondrial genomes did not reveal a clear structure. There was a lack of mitochondrial genetic differentiation between two ecotypes of cod in the eastern North Atlantic, but eastern and western cod were differentiated and mitochondrial genome diversity was higher in the eastern than the western Atlantic, suggesting deviating population histories. The geographic distribution of mitochondrial genome variation seems to be governed by demographic processes and gene flow among ecotypes that are otherwise characterized by localized genomic divergence associated with chromosomal inversions.}, } @article {pmid29921270, year = {2018}, author = {Vebrová, L and van Nieuwenhuijzen, A and Kolář, V and Boukal, DS}, title = {Seasonality and weather conditions jointly drive flight activity patterns of aquatic and terrestrial chironomids.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {19}, pmid = {29921270}, issn = {1472-6785}, support = {14-29857S//Grantová Agentura České Republiky/International ; GAJU 158/2016/P//Grantová agentura Jihočeské univerzity/International ; }, abstract = {BACKGROUND: Chironomids, a major invertebrate taxon in many standing freshwaters, rely on adult flight to reach new suitable sites, yet the impact of weather conditions on their flight activity is little understood. We investigated diel and seasonal flight activity patterns of aquatic and terrestrial chironomids in a reclaimed sandpit area and analysed how weather conditions and seasonality influenced their total abundance and species composition.

RESULTS: Air temperature, relative humidity, wind speed, and air pressure significantly affected total flight activity of both groups, but not in the same way. We identified an intermediate temperature and humidity optimum for the flight activity of terrestrial chironomids, which contrasted with weaker, timescale-dependent relationships in aquatic species. Flight activity of both groups further declined with wind speed and increased with air pressure. Observed flight patterns also varied in time on both daily and seasonal scale. Flight activity of both groups peaked in the evenings after accounting for weather conditions but, surprisingly, aquatic and terrestrial chironomids used partly alternating time windows for dispersal during the season. This may be driven by different seasonal trends of key environmental variables in larval habitats and hence implies that species phenologies and conditions experienced by chironomid larvae (and probably other aquatic insects with short-lived adults) influence adult flight patterns more than weather conditions.

CONCLUSIONS: Our results provide detailed insights into the drivers of chironomid flight activity and highlight the methodological challenges arising from the inherent collinearity of weather characteristics and their diurnal and seasonal cycles.}, } @article {pmid29921241, year = {2018}, author = {Lajhar, SA and Brownlie, J and Barlow, R}, title = {Correction to: Characterization of biofilm-forming capacity and resistance to sanitizers of a range of E.coli O26 pathotypes from clinical cases and cattle in Australia.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {61}, pmid = {29921241}, issn = {1471-2180}, abstract = {On page 4of the original publication [1], the correct sentence should read.}, } @article {pmid29921240, year = {2018}, author = {Lamb, LE and Zhi, X and Alam, F and Pyzio, M and Scudamore, CL and Wiles, S and Sriskandan, S}, title = {Modelling invasive group A streptococcal disease using bioluminescence.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {60}, pmid = {29921240}, issn = {1471-2180}, support = {BB/E52708X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; G0800720/1//National Centre for the Replacement, Refinement and Reduction of Animals in Research/International ; }, abstract = {BACKGROUND: The development of vaccines and evaluation of novel treatment strategies for invasive group A streptococcal (iGAS) disease requires suitable models of human infection that can be monitored longitudinally and are preferably non-invasive. Bio-photonic imaging provides an opportunity to reduce use of animals in infection modelling and refine the information that can be obtained, however the range of bioluminescent GAS strains available is limited. In this study we set out to develop bioluminescent iGAS strains for use in in vivo pneumonia and soft tissue disease models.

RESULTS: Using clinical emm1, emm3, and emm89 GAS strains that were transformed with constructs carrying the luxABCDE operon, growth and bioluminescence of transformed strains were characterised in vitro and in vivo. Emm3 and emm89 strains expressed detectable bioluminescence when transformed with a replicating plasmid and light production correlated with viable bacterial counts in vitro, however plasmid instability precluded use in the absence of antimicrobial pressure. Emm89 GAS transformed with an integrating construct demonstrated stable bioluminescence that was maintained in the absence of antibiotics. Bioluminescence of the emm89 strain correlated with viable bacterial counts both in vitro and immediately following infection in vivo. Although bioluminescence conferred a detectable fitness burden to the emm89 strain during soft tissue infection in vivo, it did not prevent dissemination to distant tissues.

CONCLUSION: Development of stably bioluminescent GAS for use in vitro and in vivo models of infection should facilitate development of novel therapeutics and vaccines while also increasing our understanding of infection progression and transmission routes.}, } @article {pmid29921232, year = {2018}, author = {Nunes, SC and Lopes-Coelho, F and Gouveia-Fernandes, S and Ramos, C and Pereira, SA and Serpa, J}, title = {Cysteine boosters the evolutionary adaptation to CoCl2 mimicked hypoxia conditions, favouring carboplatin resistance in ovarian cancer.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {97}, pmid = {29921232}, issn = {1471-2148}, support = {LPCC-TVi//LPCC-TVi/International ; Proj 21//iNOVA4Health/International ; }, mesh = {*Adaptation, Physiological ; *Biological Evolution ; Carboplatin/pharmacology/*therapeutic use ; Cell Hypoxia/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cobalt/*pharmacology ; Cysteine/*pharmacology ; *Drug Resistance, Neoplasm/drug effects ; Female ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Ovarian Neoplasms/*drug therapy/genetics/*pathology ; }, abstract = {BACKGROUND: Ovarian cancer is the second most common gynaecologic malignancy and the most common cause of death from gynaecologic cancer, especially due to diagnosis at an advanced stage, when a cure is rare. As ovarian tumour grows, cancer cells are exposed to regions of hypoxia. Hypoxia is known to be partially responsible for tumour progression, metastasis and resistance to therapies. These suggest that hypoxia entails a selective pressure in which the adapted cells not only have a fitness increase under the selective environment, but also in non-selective adverse environments. In here, we used two different ovarian cancer cell lines - serous carcinoma (OVCAR3) and clear cell carcinoma (ES2) - in order to address the effect of cancer cells selection under normoxia and hypoxia mimicked by cobalt chloride on the evolutionary outcome of cancer cells.

RESULTS: Our results showed that the adaptation to normoxia and CoCl2 mimicked hypoxia leads cells to display opposite strategies. Whereas cells adapted to CoCl2 mimicked hypoxia conditions tend to proliferate less but present increased survival in adverse environments, cells adapted to normoxia proliferate rapidly but at the cost of increased mortality in adverse environments. Moreover, results suggest that cysteine allows a quicker response and adaptation to hypoxic conditions that, in turn, are capable of driving chemoresistance.

CONCLUSIONS: We showed that cysteine impacts the adaptation of cancer cells to a CoCl2 mimicked hypoxic environment thus contributing for hypoxia-drived platinum-based chemotherapeutic agents' resistance, allowing the selection of more aggressive phenotypes. These observations support a role of cysteine in cancer progression, recurrence and chemoresistance.}, } @article {pmid29921229, year = {2018}, author = {Cabrera, VM and Marrero, P and Abu-Amero, KK and Larruga, JM}, title = {Carriers of mitochondrial DNA macrohaplogroup L3 basal lineages migrated back to Africa from Asia around 70,000 years ago.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {98}, pmid = {29921229}, issn = {1471-2148}, support = {CGL2010-16195//Spanish Ministerio de Ciencia e Innovación/International ; }, mesh = {Africa ; Asia ; Base Sequence ; Chromosomes, Human, Y/genetics ; Cluster Analysis ; DNA, Mitochondrial/*genetics ; Female ; Genetics, Population ; Haplotypes/*genetics ; Heterozygote ; Humans ; Male ; *Phylogeny ; Phylogeography ; Time Factors ; }, abstract = {BACKGROUND: The main unequivocal conclusion after three decades of phylogeographic mtDNA studies is the African origin of all extant modern humans. In addition, a southern coastal route has been argued for to explain the Eurasian colonization of these African pioneers. Based on the age of macrohaplogroup L3, from which all maternal Eurasian and the majority of African lineages originated, the out-of-Africa event has been dated around 60-70 kya. On the opposite side, we have proposed a northern route through Central Asia across the Levant for that expansion and, consistent with the fossil record, we have dated it around 125 kya. To help bridge differences between the molecular and fossil record ages, in this article we assess the possibility that mtDNA macrohaplogroup L3 matured in Eurasia and returned to Africa as basal L3 lineages around 70 kya.

RESULTS: The coalescence ages of all Eurasian (M,N) and African (L3) lineages, both around 71 kya, are not significantly different. The oldest M and N Eurasian clades are found in southeastern Asia instead near of Africa as expected by the southern route hypothesis. The split of the Y-chromosome composite DE haplogroup is very similar to the age of mtDNA L3. An Eurasian origin and back migration to Africa has been proposed for the African Y-chromosome haplogroup E. Inside Africa, frequency distributions of maternal L3 and paternal E lineages are positively correlated. This correlation is not fully explained by geographic or ethnic affinities. This correlation rather seems to be the result of a joint and global replacement of the old autochthonous male and female African lineages by the new Eurasian incomers.

CONCLUSIONS: These results are congruent with a model proposing an out-of-Africa migration into Asia, following a northern route, of early anatomically modern humans carrying pre-L3 mtDNA lineages around 125 kya, subsequent diversification of pre-L3 into the basal lineages of L3, a return to Africa of Eurasian fully modern humans around 70 kya carrying the basal L3 lineages and the subsequent diversification of Eurasian-remaining L3 lineages into the M and N lineages in the outside-of-Africa context, and a second Eurasian global expansion by 60 kya, most probably, out of southeast Asia. Climatic conditions and the presence of Neanderthals and other hominins might have played significant roles in these human movements. Moreover, recent studies based on ancient DNA and whole-genome sequencing are also compatible with this hypothesis.}, } @article {pmid29921228, year = {2018}, author = {Santoro, S and Lopez, ID and Lombardi, R and Zauli, A and Osiceanu, AM and Sorosina, M and Clarelli, F and Peroni, S and Cazzato, D and Marchi, M and Quattrini, A and Comi, G and Calogero, RA and Lauria, G and Martinelli Boneschi, F}, title = {Laser capture microdissection for transcriptomic profiles in human skin biopsies.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {7}, pmid = {29921228}, issn = {1471-2199}, support = {602273//FP7 Health/International ; }, mesh = {Aged ; Biopsy ; Female ; Gene Expression Profiling/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Laser Capture Microdissection/*methods ; Male ; Middle Aged ; Sequence Analysis, RNA/methods ; Skin/*pathology ; }, abstract = {BACKGROUND: The acquisition of reliable tissue-specific RNA sequencing data from human skin biopsy represents a major advance in research. However, the complexity of the process of isolation of specific layers from fresh-frozen human specimen by laser capture microdissection, the abundant presence of skin nucleases and RNA instability remain relevant methodological challenges. We developed and optimized a protocol to extract RNA from layers of human skin biopsies and to provide satisfactory quality and amount of mRNA sequencing data.

RESULTS: The protocol includes steps of collection, embedding, freezing, histological coloration and relative optimization to preserve RNA extracted from specific components of fresh-frozen human skin biopsy of 14 subjects. Optimization of the protocol includes a preservation step in RNALater® Solution, the control of specimen temperature, the use of RNase Inhibitors and the time reduction of the staining procedure. The quality of extracted RNA was measured using the percentage of fragments longer than 200 nucleotides (DV200), a more suitable measurement for successful library preparation than the RNA Integrity Number (RIN). RNA was then enriched using the TruSeq® RNA Access Library Prep Kit (Illumina®) and sequenced on HiSeq® 2500 platform (Illumina®). Quality control on RNA sequencing data was adequate to get reliable data for downstream analysis.

CONCLUSIONS: The described implemented and optimized protocol can be used for generating transcriptomics data on skin tissues, and it is potentially applicable to other tissues. It can be extended to multicenter studies, due to the introduction of an initial step of preservation of the specimen that allowed the shipment of biological samples.}, } @article {pmid29921227, year = {2018}, author = {Toussaint, EFA and Breinholt, JW and Earl, C and Warren, AD and Brower, AVZ and Yago, M and Dexter, KM and Espeland, M and Pierce, NE and Lohman, DJ and Kawahara, AY}, title = {Anchored phylogenomics illuminates the skipper butterfly tree of life.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {101}, pmid = {29921227}, issn = {1471-2148}, support = {1541557//National Science Foundation/International ; }, mesh = {Animals ; Base Sequence ; Butterflies/*classification/genetics ; *Genomics ; Likelihood Functions ; *Phylogeny ; Species Specificity ; }, abstract = {BACKGROUND: Butterflies (Papilionoidea) are perhaps the most charismatic insect lineage, yet phylogenetic relationships among them remain incompletely studied and controversial. This is especially true for skippers (Hesperiidae), one of the most species-rich and poorly studied butterfly families.

METHODS: To infer a robust phylogenomic hypothesis for Hesperiidae, we sequenced nearly 400 loci using Anchored Hybrid Enrichment and sampled all tribes and more than 120 genera of skippers. Molecular datasets were analyzed using maximum-likelihood, parsimony and coalescent multi-species phylogenetic methods.

RESULTS: All analyses converged on a novel, robust phylogenetic hypothesis for skippers. Different optimality criteria and methodologies recovered almost identical phylogenetic trees with strong nodal support at nearly all nodes and all taxonomic levels. Our results support Coeliadinae as the sister group to the remaining skippers, the monotypic Euschemoninae as the sister group to all other subfamilies but Coeliadinae, and the monophyly of Eudaminae plus Pyrginae. Within Pyrginae, Celaenorrhinini and Tagiadini are sister groups, the Neotropical firetips, Pyrrhopygini, are sister to all other tribes but Celaenorrhinini and Tagiadini. Achlyodini is recovered as the sister group to Carcharodini, and Erynnini as sister group to Pyrgini. Within the grass skippers (Hesperiinae), there is strong support for the monophyly of Aeromachini plus remaining Hesperiinae. The giant skippers (Agathymus and Megathymus) once classified as a subfamily, are recovered as monophyletic with strong support, but are deeply nested within Hesperiinae.

CONCLUSIONS: Anchored Hybrid Enrichment sequencing resulted in a large amount of data that built the foundation for a new, robust evolutionary tree of skippers. The newly inferred phylogenetic tree resolves long-standing systematic issues and changes our understanding of the skipper tree of life. These resultsenhance understanding of the evolution of one of the most species-rich butterfly families.}, } @article {pmid29921226, year = {2018}, author = {Cotoras, DD and Bi, K and Brewer, MS and Lindberg, DR and Prost, S and Gillespie, RG}, title = {Co-occurrence of ecologically similar species of Hawaiian spiders reveals critical early phase of adaptive radiation.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {100}, pmid = {29921226}, issn = {1471-2148}, support = {S10 RR027303/RR/NCRR NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; DEB 1241253//Directorate for Biological Sciences/International ; }, mesh = {*Adaptation, Physiological ; Animals ; *Ecological and Environmental Phenomena ; Exons/genetics ; Gene Flow ; Genetic Variation ; Geography ; Hawaii ; Nucleotides/genetics ; Phylogeny ; Principal Component Analysis ; Species Specificity ; Spiders/genetics/*physiology ; Statistics as Topic ; Transcriptome/genetics ; }, abstract = {BACKGROUND: The processes through which populations originate and diversify ecologically in the initial stages of adaptive radiation are little understood because we lack information on critical steps of early divergence. A key question is, at what point do closely related species interact, setting the stage for competition and ecological specialization? The Hawaiian Islands provide an ideal system to explore the early stages of adaptive radiation because the islands span ages from 0.5-5 Mya. Hawaiian spiders in the genus Tetragnatha have undergone adaptive radiation, with one lineage ("spiny legs") showing four different ecomorphs (green, maroon, large brown, small brown); one representative of each ecomorph is generally found at any site on the older islands. Given that the early stages of adaptive radiation are characterized by allopatric divergence between populations of the same ecomorph, the question is, what are the steps towards subsequent co-occurrence of different ecomorphs? Using a transcriptome-based exon capture approach, we focus on early divergence among close relatives of the green ecomorph to understand processes associated with co-occurrence within the same ecomorph at the early stages of adaptive radiation.

RESULTS: The major outcomes from the current study are first that closely related species within the same green ecomorph of spiny leg Tetragnatha co-occur on the same single volcano on East Maui, and second that there is no evidence of genetic admixture between these ecologically equivalent species. Further, that multiple genetic lineages exist on a single volcano on Maui suggests that there are no inherent dispersal barriers and that the observed limited distribution of taxa reflects competitive exclusion.

CONCLUSIONS: The observation of co-occurrence of ecologically equivalent species on the young volcano of Maui provides a missing link in the process of adaptive radiation between the point when recently divergent species of the same ecomorph occur in allopatry, to the point where different ecomorphs co-occur at a site, as found throughout the older islands. More importantly, the ability of close relatives of the same ecomorph to interact, without admixture, may provide the conditions necessary for ecological divergence and independent evolution of ecomorphs associated with adaptive radiation.}, } @article {pmid29921224, year = {2018}, author = {Chang, KW and Tseng, YT and Chen, YC and Yu, CY and Liao, HF and Chen, YC and Tu, YE and Wu, SC and Liu, IH and Pinskaya, M and Morillon, A and Pain, B and Lin, SP}, title = {Correction to: Stage-dependent piRNAs in chicken implicated roles in modulating male germ cell development.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {480}, pmid = {29921224}, issn = {1471-2164}, abstract = {Following publication of the original article [1], the authors reported that one of the authors' names is spelled incorrectly.}, } @article {pmid29921221, year = {2018}, author = {Cha, S and Lim, JE and Park, AY and Do, JH and Lee, SW and Shin, C and Cho, NH and Kang, JO and Nam, JM and Kim, JS and Woo, KM and Lee, SH and Kim, JY and Oh, B}, title = {Identification of five novel genetic loci related to facial morphology by genome-wide association studies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {481}, pmid = {29921221}, issn = {1471-2164}, support = {2006-2005173//Ministry of Science, ICT and Future Planning/ ; 2006-2005175//Ministry of Science, ICT and Future Planning/ ; Forensic Science Research Project 2014//Supreme Prosecutors' Office/ ; K18092//the research program of Korea Institute of Oriental Medicine/ ; }, mesh = {Aged ; Female ; Gene Frequency/genetics ; Genetic Loci/*genetics ; Genetic Predisposition to Disease/genetics ; Genome-Wide Association Study/*methods ; Genotype ; Homeodomain Proteins/genetics ; Humans ; Male ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide/*genetics ; SOX9 Transcription Factor/genetics ; }, abstract = {BACKGROUND: Face morphology is strongly determined by genetic factors. However, only a small number of genes related to face morphology have been identified to date. Here, we performed a two-stage genome-wide association study (GWAS) of 85 face morphological traits in 7569 Koreans (5643 in the discovery set and 1926 in the replication set).

RESULTS: In this study, we analyzed 85 facial traits, including facial angles. After discovery GWAS, 128 single nucleotide polymorphisms (SNPs) showing an association of P < 5 × 10- 6 were selected to determine the replication of the associations, and meta-analysis of discovery GWAS and the replication analysis resulted in five genome-wide significant loci. The OSR1-WDR35 [rs7567283, G allele, beta (se) = -0.536 (0.096), P = 2.75 × 10- 8] locus was associated with the facial frontal contour; the HOXD1-MTX2 [rs970797, A allele, beta (se) = 0.015 (0.003), P = 3.97 × 10- 9] and WDR27 [rs3736712, C allele, beta (se) = 0.293 (0.048), P = 8.44 × 10- 10] loci were associated with eye shape; and the SOX9 [rs2193054, C allele, beta (se) (ln-transformed) = -0.007 (0.001), P = 6.17 × 10- 17] and DHX35 [rs2206437, A allele, beta (se) = -0.283 (0.047), P = 1.61 × 10- 9] loci were associated with nose shape. WDR35 and SOX9 were related to known craniofacial malformations, i.e., cranioectodermal dysplasia 2 and campomelic dysplasia, respectively. In addition, we found three independent association signals in the SOX9 locus, and six known loci for nose size and shape were replicated in this study population. Interestingly, four SNPs within these five face morphology-related loci showed discrepancies in allele frequencies among ethnic groups.

CONCLUSIONS: We identified five novel face morphology loci that were associated with facial frontal contour, nose shape, and eye shape. Our findings provide useful genetic information for the determination of face morphology.}, } @article {pmid29921219, year = {2018}, author = {Verrier, ER and Genet, C and Laloë, D and Jaffrezic, F and Rau, A and Esquerre, D and Dechamp, N and Ciobotaru, C and Hervet, C and Krieg, F and Jouneau, L and Klopp, C and Quillet, E and Boudinot, P}, title = {Genetic and transcriptomic analyses provide new insights on the early antiviral response to VHSV in resistant and susceptible rainbow trout.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {482}, pmid = {29921219}, issn = {1471-2164}, support = {Institutional funding//INRA/ ; funding from Animal Health division and Animal genetics divisions//INRA/ ; DPMA/CIPA/INRA No. 2004/190//Ministry of Science and Technology/ ; FP7-228394//FP7 Research infrastructures (Nadir)/ ; }, mesh = {Animals ; Cell Line ; Disease Susceptibility/metabolism ; Fish Diseases/*genetics ; Gene Expression Profiling/methods ; High-Throughput Nucleotide Sequencing ; Immunity, Innate/genetics ; Interferons/genetics/metabolism ; Oncorhynchus mykiss/*genetics/physiology ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: The viral hemorrhagic septicemia virus (VHSV) is a major threat for salmonid farming and for wild fish populations worldwide. Previous studies have highlighted the importance of innate factors regulated by a major quantitative trait locus (QTL) for the natural resistance to waterborne VHSV infection in rainbow trout. The aim of this study was to analyze the early transcriptomic response to VHSV inoculation in cell lines derived from previously described resistant and susceptible homozygous isogenic lines of rainbow trout to obtain insights into the molecular mechanisms responsible for the resistance to the viral infection.

RESULTS: We first confirmed the presence of the major QTL in a backcross involving a highly resistant fish isogenic line (B57) and a highly susceptible one (A22), and were able to define the confidence interval of the QTL and to identify its precise position. We extended the definition of the QTL since it controls not only resistance to waterborne infection but also the kinetics of mortality after intra-peritoneal injection. Deep sequencing of the transcriptome of B57 and A22 derived cell lines exposed to inactivated VHSV showed a stronger response to virus inoculation in the resistant background. In line with our previous observations, an early and strong induction of interferon and interferon-stimulated genes was correlated with the resistance to VHSV, highlighting the major role of innate immune factors in natural trout resistance to the virus. Interestingly, major factors of the antiviral innate immunity were much more expressed in naive B57 cells compared to naive A22 cells, which likely contributes to the ability of B57 to mount a fast antiviral response after viral infection. These observations were further extended by the identification of several innate immune-related genes localized close to the QTL area on the rainbow trout genome.

CONCLUSIONS: Taken together, our results improve our knowledge in virus-host interactions in vertebrates and provide novel insights in the molecular mechanisms explaining the resistance to VHSV in rainbow trout. Our data also provide a collection of potential markers for resistance and susceptibility of rainbow trout to VHSV infection.}, } @article {pmid29921218, year = {2018}, author = {Majd, S and Power, JHT and Chataway, TK and Grantham, HJM}, title = {A comparison of LKB1/AMPK/mTOR metabolic axis response to global ischaemia in brain, heart, liver and kidney in a rat model of cardiac arrest.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {7}, pmid = {29921218}, issn = {1471-2121}, support = {RPF13/771//Australian Resuscitation Council/International ; 39468//Flinders University/International ; }, mesh = {AMP-Activated Protein Kinases/*metabolism ; Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Brain/blood supply/pathology ; Disease Models, Animal ; Electrocardiography ; Heart Arrest/*metabolism/*pathology ; Ischemia/*metabolism/pathology ; Kidney/blood supply/pathology ; Liver/blood supply/pathology ; Myocardium/pathology ; *Organ Specificity ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Rats, Sprague-Dawley ; *Signal Transduction ; TOR Serine-Threonine Kinases/*metabolism ; }, abstract = {BACKGROUND: Cellular energy failure in high metabolic rate organs is one of the underlying causes for many disorders such as neurodegenerative diseases, cardiomyopathies, liver and renal failures. In the past decade, numerous studies have discovered the cellular axis of LKB1/AMPK/mTOR as an essential modulator of cell homeostasis in response to energy stress. Through regulating adaptive mechanisms, this axis adjusts the energy availability to its demand by a systematized control on metabolism. Energy stress, however, could be sensed at different levels in various tissues, leading to applying different strategies in response to hypoxic insults.

METHODS: Here the immediate strategies of high metabolic rate organs to time-dependent short episodes of ischaemia were studied by using a rat model (n = 6/group) of cardiac arrest (CA) (15 and 30 s, 1, 2, 4 and 8 min CA). Using western blot analysis, we examined the responses of LKB1/AMPK/mTOR pathway in brain, heart, liver and kidney from 15 s up to 8 min of global ischaemia. The ratio of ADP/ATP was assessed in all ischemic and control groups, using ApoSENSOR bioluminescent assay kit.

RESULTS: Brain, followed by kidney showed the early dephosphorylation response in AMPK (Thr172) and LKB1 (Ser431); in the absence of ATP decline (ADP/ATP elevation). Dephosphorylation of AMPK was followed by rephosphorylation and hyperphosphorylation, which was associated with a significant ATP decline. While heart's activity of AMPK and LKB1 remained at the same level during short episodes of ischaemia, liver's LKB1 was dephosphorylated after 2 min. AMPK response to ischaemia in liver was mainly based on an early alternative and a late constant hyperphosphorylation. No significant changes was observed in mTOR activity in all groups.

CONCLUSION: Together our results suggest that early AMPK dephosphorylation followed by late hyperphosphorylation is the strategy of brain and kidney in response to ischaemia. While the liver seemed to get benefit of its AMPK system in early ischameia, possibly to stabilize ATP, the level of LKB1/AMPK activity in heart remained unchanged in short ischaemic episodes up to 8 min. Further researches must be conducted to elucidate the molecular mechanism underlying LKB1/AMPK response to oxygen supply.}, } @article {pmid29921216, year = {2018}, author = {Appelgren, ASC and Saladin, V and Richner, H and Doligez, B and McCoy, KD}, title = {Gene flow and adaptive potential in a generalist ectoparasite.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {99}, pmid = {29921216}, issn = {1471-2148}, support = {31003A_122566//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; Explora'Doc//Region Rhône Alpes/International ; }, mesh = {*Adaptation, Physiological ; Animals ; Chickens ; Discriminant Analysis ; *Gene Flow ; Genetic Loci ; Genetic Markers ; Genetic Variation ; Genetics, Population ; Geography ; Host Specificity/genetics ; Host-Parasite Interactions/genetics ; Microsatellite Repeats ; Parasites/*genetics/*physiology ; Principal Component Analysis ; Siphonaptera/*genetics/*physiology ; Songbirds/parasitology ; }, abstract = {BACKGROUND: In host-parasite systems, relative dispersal rates condition genetic novelty within populations and thus their adaptive potential. Knowledge of host and parasite dispersal rates can therefore help us to understand current interaction patterns in wild populations and why these patterns shift over time and space. For generalist parasites however, estimates of dispersal rates depend on both host range and the considered spatial scale. Here, we assess the relative contribution of these factors by studying the population genetic structure of a common avian ectoparasite, the hen flea Ceratophyllus gallinae, exploiting two hosts that are sympatric in our study population, the great tit Parus major and the collared flycatcher Ficedula albicollis. Previous experimental studies have indicated that the hen flea is both locally maladapted to great tit populations and composed of subpopulations specialized on the two host species, suggesting limited parasite dispersal in space and among hosts, and a potential interaction between these two structuring factors.

RESULTS: C. gallinae fleas were sampled from old nests of the two passerine species in three replicate wood patches and were genotyped at microsatellite markers to assess population genetic structure at different scales (among individuals within a nest, among nests and between host species within a patch and among patches). As expected, significant structure was found at all spatial scales and between host species, supporting the hypothesis of limited dispersal in this parasite. Clustering analyses and estimates of relatedness further suggested that inbreeding regularly occurs within nests. Patterns of isolation by distance within wood patches indicated that flea dispersal likely occurs in a stepwise manner among neighboring nests. From these data, we estimated that gene flow in the hen flea is approximately half that previously described for its great tit hosts.

CONCLUSION: Our results fall in line with predictions based on observed patterns of adaptation in this host-parasite system, suggesting that parasite dispersal is limited and impacts its adaptive potential with respect to its hosts. More generally, this study sheds light on the complex interaction between parasite gene flow, local adaptation and host specialization within a single host-parasite system.}, } @article {pmid29921035, year = {2018}, author = {Marozava, S and Vargas-López, R and Tian, Y and Merl-Pham, J and Braster, M and Meckenstock, RU and Smidt, H and Röling, WFM and Westerhoff, HV}, title = {Metabolic flexibility of a prospective bioremediator: Desulfitobacterium hafniense Y51 challenged in chemostats.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2652-2669}, doi = {10.1111/1462-2920.14295}, pmid = {29921035}, issn = {1462-2920}, abstract = {Desulfitobacterium hafniense Y51 has been widely used in investigations of perchloroethylene (PCE) biodegradation, but limited information exists on its other physiological capabilities. We investigated how D. hafniense Y51 confronts the debilitating limitations of not having enough electron donor (lactate), or electron acceptor (fumarate) during cultivation in chemostats. The residual concentrations of the substrates supplied in excess were much lower than expected. Transcriptomics, proteomics and fluxomics were integrated to investigate how this phenomenon was regulated. Through diverse regulation at both transcriptional and translational levels, strain Y51 turned to fermenting the excess lactate and disproportionating the excess fumarate under fumarate- and lactate-limiting conditions respectively. Genes and proteins related to the utilization of a variety of alternative electron donors and acceptors absent from the medium were induced, apparently involving the Wood-Ljungdahl pathway. Through this metabolic flexibility, D. hafniense Y51 may be able to switch between different metabolic capabilities under limiting conditions.}, } @article {pmid29921019, year = {2018}, author = {Menanteau, P and Kempf, F and Trotereau, J and Virlogeux-Payant, I and Gitton, E and Dalifard, J and Gabriel, I and Rychlik, I and Velge, P}, title = {Role of systemic infection, cross contaminations and super-shedders in Salmonella carrier state in chicken.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3246-3260}, doi = {10.1111/1462-2920.14294}, pmid = {29921019}, issn = {1462-2920}, abstract = {Carriage of Salmonella is often associated with a high level of bacterial excretion and generally occurs after a short systemic infection. However, we do not know whether this systemic infection is required or whether the carrier-state corresponds to continuous reinfection or real persistence in caecal tissue. The use of a Salmonella Enteritidis bamB mutant demonstrated that a carrier-state could be obtained in chicken in the absence of systemic infection. The development of a new infection model in isolator showed that a marked decrease in animal reinfection and host-to-host transmission between chicks led to a heterogeneity of S. Enteritidis excretion and colonization contrary to what was observed in cages. This heterogeneity of infection was characterized by the presence of super-shedders, which constantly disseminated Salmonella to the low-shedder chicks, mainly through airborne movements of contaminated dust particles. The presence of super-shedders, in the absence of host-to-host transmission, demonstrated that constant reinfection was not required to induce a carrier-state. Finally, our results suggest that low-shedder chicks do not have a higher capability to destroy Salmonella but instead can block initial Salmonella colonization. This new paradigm opens new avenues to improve understanding of the carrier-state mechanisms and to define new strategies to control Salmonella infections.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid29921018, year = {2018}, author = {Lamouche, F and Gully, D and Chaumeret, A and Nouwen, N and Verly, C and Pierre, O and Sciallano, C and Fardoux, J and Jeudy, C and Szücs, A and Mondy, S and Salon, C and Nagy, I and Kereszt, A and Dessaux, Y and Giraud, E and Mergaert, P and Alunni, B}, title = {Transcriptomic dissection of Bradyrhizobium sp. strain ORS285 in symbiosis with Aeschynomene spp. inducing different bacteroid morphotypes with contrasted symbiotic efficiency.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14292}, pmid = {29921018}, issn = {1462-2920}, abstract = {To circumvent the paucity of nitrogen sources in the soil legume plants establish a symbiotic interaction with nitrogen-fixing soil bacteria called rhizobia. During symbiosis, the plants form root organs called nodules, where bacteria are housed intracellularly and become active nitrogen fixers known as bacteroids. Depending on their host plant, bacteroids can adopt different morphotypes, being either unmodified (U), elongated (E) or spherical (S). E- and S-type bacteroids undergo a terminal differentiation leading to irreversible morphological changes and DNA endoreduplication. Previous studies suggest that differentiated bacteroids display an increased symbiotic efficiency (E > U and S > U). In this study, we used a combination of Aeschynomene species inducing E- or S-type bacteroids in symbiosis with Bradyrhizobium sp. ORS285 to show that S-type bacteroids present a better symbiotic efficiency than E-type bacteroids. We performed a transcriptomic analysis on E- and S-type bacteroids formed by Aeschynomene afraspera and Aeschynomene indica nodules and identified the bacterial functions activated in bacteroids and specific to each bacteroid type. Extending the expression analysis in E- and S-type bacteroids in other Aeschynomene species by qRT-PCR on selected genes from the transcriptome analysis narrowed down the set of bacteroid morphotype-specific genes. Functional analysis of a selected subset of 31 bacteroid-induced or morphotype-specific genes revealed no symbiotic phenotypes in the mutants. This highlights the robustness of the symbiotic program but could also indicate that the bacterial response to the plant environment is partially anticipatory or even maladaptive. Our analysis confirms the correlation between differentiation and efficiency of the bacteroids and provides a framework for the identification of bacterial functions that affect the efficiency of bacteroids.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid29921005, year = {2018}, author = {Tran, P and Ramachandran, A and Khawasik, O and Beisner, BE and Rautio, M and Huot, Y and Walsh, DA}, title = {Microbial life under ice: Metagenome diversity and in situ activity of Verrucomicrobia in seasonally ice-covered Lakes.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2568-2584}, doi = {10.1111/1462-2920.14283}, pmid = {29921005}, issn = {1462-2920}, abstract = {Northern lakes are ice-covered for a large part of the year, yet our understanding of microbial diversity and activity during winter lags behind that of the ice-free period. In this study, we investigated under-ice diversity and metabolism of Verrucomicrobia in seasonally ice-covered lakes in temperate and boreal regions of Quebec, Canada using 16S rRNA sequencing, metagenomics and metatranscriptomics. Verrucomicrobia, particularly the V1, V3 and V4 subdivisions, were abundant during ice-covered periods. A diversity of Verrucomicrobia genomes were reconstructed from Quebec lake metagenomes. Several genomes were associated with the ice-covered period and were represented in winter metatranscriptomes, supporting the notion that Verrucomicrobia are metabolically active under ice. Verrucomicrobia transcriptome analysis revealed a range of metabolisms potentially occurring under ice, including carbohydrate degradation, glycolate utilization, scavenging of chlorophyll degradation products, and urea use. Genes for aerobic sulfur and hydrogen oxidation were expressed, suggesting chemolithotrophy may be an adaptation to conditions where labile carbon may be limited. The expression of genes for flagella biosynthesis and chemotaxis was detected, suggesting Verrucomicrobia may be actively sensing and responding to winter nutrient pulses, such as phytoplankton blooms. These results increase our understanding on the diversity and metabolic processes occurring under ice in northern lakes ecosystems.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid29921003, year = {2018}, author = {Happel, E and Bartl, I and Voss, M and Riemann, L}, title = {Extensive nitrification and active ammonia oxidizers in two contrasting coastal systems of the Baltic Sea.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2913-2926}, doi = {10.1111/1462-2920.14293}, pmid = {29921003}, issn = {1462-2920}, support = {Art 185//BONUS Blueprint and BONUS Cocoa/ ; //European Union's Seventh Programme for research/ ; 3051-00002B//The Danish Council for Strategic Research/ ; 03F0683A//German Ministry of Education and Science/ ; }, abstract = {Nitrification is important in nitrogen (N) cycling of aquatic environments, but knowledge about its regulation and importance is sparse. Here we examined nitrification and ammonia oxidizers in the Baltic Sea. We investigated two sites with different catchment characteristics (agricultural and forest), the Bay of Gdánsk (south) and the Öre Estuary (north), and measured pelagic nitrification rates and abundance, composition and expression of ammonia monooxygenase (amoA) genes. Highest nitrification rates were found in the nutrient rich Bay of Gdańsk. Interestingly, abundances of ammonia-oxidizing archaea (AOA) and bacteria (AOB) were orders of magnitude lower than reported from other sites. Although AOA were most abundant at both sites, the highest expression levels were from AOB. Interestingly, few AOA and AOB taxa dominated amoA gene expression, with a Nitrosomarinus related phylotype showing widespread expression. AOA and AOB communities differed between sites and depths, respectively, with the composition in rivers being distinct. A storm event, causing an even depth distribution of nitrification and particles in the Bay of Gdańsk, indicated that the presence of particles stimulate nitrification. The study highlights coastal regions as dynamic sites of extensive pelagic nitrification, which may affect local food web dynamics and loss of N mediated by denitrification.}, } @article {pmid29921002, year = {2018}, author = {Nissimov, JI and Vandzura, R and Johns, CT and Natale, F and Haramaty, L and Bidle, KD}, title = {Dynamics of transparent exopolymer particle production and aggregation during viral infection of the coccolithophore, Emiliania huxleyi.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2880-2897}, doi = {10.1111/1462-2920.14261}, pmid = {29921002}, issn = {1462-2920}, support = {GBMF3789//Gordon and Betty Moore Foundation/ ; OCE-1459200//National Science Foundation/ ; OCE-1537951//National Science Foundation/ ; }, abstract = {Emiliania huxleyi produces calcium carbonate (CaCO3) coccoliths and transparent exopolymer particles (TEP), sticky, acidic carbohydrates that facilitate aggregation. E. huxleyi's extensive oceanic blooms are often terminated by coccolithoviruses (EhVs) with the transport of cellular debris and associated particulate organic carbon (POC) to depth being facilitated by TEP-bound 'marine snow' aggregates. The dynamics of TEP production and particle aggregation in response to EhV infection are poorly understood. Using flow cytometry, spectrophotometry and FlowCam visualization of alcian blue (AB)-stained aggregates, we assessed TEP production and the size spectrum of aggregates for E. huxleyi possessing different degrees of calcification and cellular CaCO3 :POC mass ratios, when challenged with two EhVs (EhV207 and EhV99B1). FlowCam imaging also qualitatively assessed the relative amount of AB-stainable TEP (i.e., blue:red ratio of each particle). We show significant increases in TEP during early phase EhV207-infection (∼ 24 h) of calcifying strains and a shift towards large aggregates following EhV99B1-infection. We also observed the formation of large aggregates with low blue:red ratios, suggesting that other exopolymer substances contribute towards aggregation. Our findings show the potential for virus infection and the associated response of their hosts to impact carbon flux dynamics and provide incentive to explore these dynamics in natural populations.}, } @article {pmid29920907, year = {2018}, author = {Potapov, AM and Tiunov, AV and Scheu, S}, title = {Uncovering trophic positions and food resources of soil animals using bulk natural stable isotope composition.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12434}, pmid = {29920907}, issn = {1469-185X}, abstract = {Despite the major importance of soil biota in nutrient and energy fluxes, interactions in soil food webs are poorly understood. Here we provide an overview of recent advances in uncovering the trophic structure of soil food webs using natural variations in stable isotope ratios. We discuss approaches of application, normalization and interpretation of stable isotope ratios along with methodological pitfalls. Analysis of published data from temperate forest ecosystems is used to outline emerging concepts and perspectives in soil food web research. In contrast to aboveground and aquatic food webs, trophic fractionation at the basal level of detrital food webs is large for carbon and small for nitrogen stable isotopes. Virtually all soil animals are enriched in 13 C as compared to plant litter. This 'detrital shift' likely reflects preferential uptake of 13 C-enriched microbial biomass and underlines the importance of microorganisms, in contrast to dead plant material, as a major food resource for the soil animal community. Soil organic matter is enriched in 15 N and 13 C relative to leaf litter. Decomposers inhabiting mineral soil layers therefore might be enriched in 15 N resulting in overlap in isotope ratios between soil-dwelling detritivores and litter-dwelling predators. By contrast, 13 C content varies little between detritivores in upper litter and in mineral soil, suggesting that they rely on similar basal resources, i.e. little decomposed organic matter. Comparing vertical isotope gradients in animals and in basal resources can be a valuable tool to assess trophic interactions and dynamics of organic matter in soil. As indicated by stable isotope composition, direct feeding on living plant material as well as on mycorrhizal fungi is likely rare among soil invertebrates. Plant carbon is taken up predominantly by saprotrophic microorganisms and channelled to higher trophic levels of the soil food web. However, feeding on photoautotrophic microorganisms and non-vascular plants may play an important role in fuelling soil food webs. The trophic niche of most high-rank animal taxa spans at least two trophic levels, implying the use of a wide range of resources. Therefore, to identify trophic species and links in food webs, low-rank taxonomic identification is required. Despite overlap in feeding strategies, stable isotope composition of the high-rank taxonomic groups reflects differences in trophic level and in the use of basal resources. Different taxonomic groups of predators and decomposers are likely linked to different pools of organic matter in soil, suggesting different functional roles and indicating that trophic niches in soil animal communities are phylogenetically structured. During last two decades studies using stable isotope analysis have elucidated the trophic structure of soil communities, clarified basal food resources of the soil food web and revealed links between above- and belowground ecosystem compartments. Extending the use of stable isotope analysis to a wider range of soil-dwelling organisms, including microfauna, and a larger array of ecosystems provides the perspective of a comprehensive understanding of the structure and functioning of soil food webs.}, } @article {pmid29920668, year = {2018}, author = {Martinez, CM and McGee, MD and Borstein, SR and Wainwright, PC}, title = {Feeding ecology underlies the evolution of cichlid jaw mobility.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13518}, pmid = {29920668}, issn = {1558-5646}, abstract = {The fish feeding apparatus is among the most diverse functional systems in vertebrates. While morphological and mechanical variations of feeding systems are well studied, we know far less about the diversity of the motions that they produce. We explored patterns of feeding movements in African cichlids from Lakes Malawi and Tanganyika, asking whether the degree of kinesis is associated with dietary habits of species. We used geometric morphometrics to measure feeding kinesis as trajectories of shape change, based on 326 high-speed videos in 56 species. Cranial morphology was significantly related to feeding movements, both of which were distributed along a dietary axis associated with prey evasiveness. Small-mouthed cichlids that feed by scraping algae and detritus from rocks had low kinesis strikes, while large-mouthed species that eat large, evasive prey (fishes and shrimps) generated the greatest kinesis. Despite having higher overall kinesis, comparisons of trajectory shape (linearity) revealed that cichlids that eat mobile prey also displayed more kinematically conserved, or efficient, feeding motions. Our work indicates that prey evasiveness is strongly related to the evolution of cichlid jaw mobility, suggesting that this same relationship may explain the origins and diversity of highly kinetic jaws that characterize the super-radiation of spiny-rayed fishes.}, } @article {pmid29920667, year = {2018}, author = {Kranz, AM and Forgan, LG and Cole, GL and Endler, JA}, title = {Light environment change induces differential expression of guppy opsins in a multi-generational evolution experiment.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13519}, pmid = {29920667}, issn = {1558-5646}, abstract = {Light environments critically impact species that rely on vision to survive and reproduce. Animal visual systems must accommodate changes in light that occur from minutes to years, yet the mechanistic basis of their response to spectral (color) changes is largely unknown. Here, we used a laboratory experiment where replicate guppy populations were kept under three different light environments for up to 8-12 generations to explore possible differences in the expression levels of nine guppy opsin genes. Previous evidence for opsin expression-light environment "tuning" has been either correlative or focused exclusively on the relationship between the light environment and opsin expression over one or two generations. In our multigeneration experiment, the relative expression levels of nine different guppy opsin genes responded differently to light environment changes: some did not respond, while others differed due to phenotypic plasticity. Moreover, for the LWS-1 opsin we found that, while we observed a wide range of plastic responses under different light conditions, common plastic responses (where the population replicates all followed the same trajectory) occurred only after multigenerational exposure to different light environments. Taken together this suggests that opsin expression plasticity plays an important role in light environment "tuning" in different light environments on different time scales, and, in turn, has important implications for both visual system function and evolution.}, } @article {pmid29920665, year = {2018}, author = {Au, KLE}, title = {Digest: The evolution of sexual imprinting as an assortative mating mechanism.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13527}, pmid = {29920665}, issn = {1558-5646}, abstract = {In this issue, Yeh et al. (2018) investigated whether sexual imprinting could act as an assortative mating mechanism, reducing hybridization and increasing premating isolation. While they indeed find that imprinting leads to assortative mating and reduced hybridization, the strength at which imprinting evolves is usually intermediate, because it is counterbalanced by the costs of imprinting and the benefits of adaptive hybridization. Thus, while sexual imprinting can act as an assortative mating mechanism, it is often not the sole element of female mate choice.}, } @article {pmid29920477, year = {2018}, author = {Lynch, KS and Louder, MIM and Hauber, ME}, title = {Species-Specific Auditory Forebrain Responses to Non-Learned Vocalizations in Juvenile Blackbirds.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {4}, pages = {193-200}, doi = {10.1159/000489115}, pmid = {29920477}, issn = {1421-9743}, abstract = {Species recognition mediates the association of individuals with conspecifics. Learned cues often facilitate species recognition via early social experience with parents and siblings. Yet, in some songbirds, the production of species-typical vocalizations develops in the absence of early social experiences. Here, we investigate the auditory-evoked neural responses of juvenile red-winged blackbirds (Agelaius phoeniceus), a nonparasitic (parental) species within the Icterid family and contrast these results with a closely related Icterid parasitic species that lacks parental care, the brown-headed cowbird (Molothrus ater). We demonstrate that immediate early gene (IEG) activity in the caudomedial mesopallium (CMM) is selectively evoked in response to conspecific non-learned vocalizations in comparison to 2 types of heterospecific non-learned vocalizations, independent of the acoustic similarity patterns between the playback stimuli. This pattern, however, was not detected in the caudomedial nidopallium (NCM). Because the red-winged blackbird is a parental species, the conspecific non-learned vocalization is presumably a familiar sound to the juvenile red-winged blackbird, whereas the heterospecific non-learned vocalizations are novel. We contrast results reported here with our recent demonstration of selective IEG induction in response to non-learned conspecific vocalizations in juvenile parasitic brown-headed cowbirds, in which conspecific non-learned vocalizations are presumably novel. In this case, selective IEG induction from conspecific non-learned vocalization occurred within NCM but not within CMM. By comparing closely related species with stark differences in the early exposure to conspecifics, we demonstrate that CMM and NCM respond to familiar vs. novel non-learned vocalizations in a manner that parallel previously reported regional responses to learned vocalizations such as conspecific songs.}, } @article {pmid29920336, year = {2018}, author = {Liu, Z and Chen, G and Zhu, T and Zeng, Z and Lyu, Z and Wang, J and Messenger, K and Greenberg, AJ and Guo, Z and Yang, Z and Shi, S and Wang, Y}, title = {Prevalence of cryptic species in morphologically uniform taxa - Fast speciation and evolutionary radiation in Asian frogs.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {723-731}, doi = {10.1016/j.ympev.2018.06.020}, pmid = {29920336}, issn = {1095-9513}, abstract = {Diversity and distributions of cryptic species have long been a vexing issue. Identification of species boundaries is made difficult by the lack of obvious morphological differences. Here, we investigate the cryptic diversity and evolutionary history of an underappreciated group of Asian frog species (Megophrys) to explore the pattern and dynamic of amphibian cryptic species. We sequenced four mitochondrial genes and five nuclear genes and delineated species using multiple approaches, combining DNA and mating-call data. A Bayesian species tree was generated to estimate divergence times and to reconstruct ancestral ranges. Macroevolutionary analyses and hybridization tests were conducted to explore the evolutionary dynamics of this cryptic group. Our phylogenies support the current subgenera. We revealed 43 cryptic species, 158% higher than previously thought. The species-delimitation results were further confirmed by mating-call data and morphological divergence. We found that these Asian frogs entered China from the Sunda Shelf 48 Mya, followed by an ancient radiation event during middle Miocene. We confirmed the efficiency of the multispecies coalescent model for delimitation of species with low morphological diversity. Species diversity of Megophrys is severely underappreciated, and species distributions have been misestimated as a result.}, } @article {pmid29920335, year = {2018}, author = {Fields, PD and Obbard, DJ and McTaggart, SJ and Galimov, Y and Little, TJ and Ebert, D}, title = {Mitogenome phylogeographic analysis of a planktonic crustacean.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {138-148}, doi = {10.1016/j.ympev.2018.06.028}, pmid = {29920335}, issn = {1095-9513}, abstract = {Phylogeography places population genetics in an explicitly spatial context, and in doing so attempts to reconstruct the historical and contemporary evolutionary processes acting across a species range through space and time. Here we present the phylogeographical structure of Daphnia magna as determined for full mitochondrial genomes from samples of 60 populations throughout much of the species known range, including Europe, the Middle East, and Asia. Contrary to previous analyses, the present analysis of the mitochondrial genome reveals coarse-grained (continental scale) evidence for spatial structure, and in particular a deep split between Western Eurasia and East Asian D. magna lineages. In contrast to previous analyses with nuclear genetic markers, our mitogenomic analysis reveals much less structure within lineages. We quantify divergence between species using the full mitochondrial genome sequence of a closely related species, D. similis. The distribution of European and Middle Eastern genetic diversity is consistent with a rapid demographic expansion following the end of the most recent ice age about 10,000 years before present. By estimating species wide distributions of dN/dS in mtDNA, we provide evidence that the effectiveness of purifying selection on protein coding genes in the mitochondrial genome of coastal rock pool populations, which have pronounced extinction-colonization dynamics, is reduced compared to larger and more stable non-rock pool populations. The present study adds important insights into the evolutionary history of a widely used model organism in ecology, evolution and ecotoxicology, and highlights the utility of phylogeographic analysis of organellar genomes to understand evolutionary processes.}, } @article {pmid29920253, year = {2018}, author = {Swid, N and Nevo, R and Kiss, V and Kapon, R and Dagan, S and Snir, O and Adam, Z and Falconet, D and Reich, Z and Charuvi, D}, title = {Differential impacts of FtsZ proteins on plastid division in the shoot apex of Arabidopsis.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {83-94}, doi = {10.1016/j.ydbio.2018.06.010}, pmid = {29920253}, issn = {1095-564X}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Chloroplasts/genetics/*metabolism ; Meristem/genetics/*metabolism ; Plant Leaves/genetics/*metabolism ; Protein Isoforms/genetics/metabolism ; }, abstract = {FtsZ proteins of the FtsZ1 and FtsZ2 families play important roles in the initiation and progression of plastid division in plants and green algae. Arabidopsis possesses a single FTSZ1 member and two FTSZ2 members, FTSZ2-1 and FTSZ2-2. The contribution of these to chloroplast division and partitioning has been mostly investigated in leaf mesophyll tissues. Here, we assessed the involvement of the three FtsZs in plastid division at earlier stages of chloroplast differentiation. To this end, we studied the effect of the absence of specific FtsZ proteins on plastids in the vegetative shoot apex, where the proplastid-to-chloroplast transition takes place. We found that the relative contribution of the two major leaf FtsZ isoforms, FtsZ1 and FtsZ2-1, to the division process varies with cell lineage and position within the shoot apex. While FtsZ2-1 dominates division in the L1 and L3 layers of the shoot apical meristem (SAM), in the L2 layer, FtsZ1 and FtsZ2-1 contribute equally toward the process. Depletion of the third isoform, FtsZ2-2, generally resulted in stronger effects in the shoot apex than those observed in mature leaves. The implications of these findings, along with additional observations made in this work, to our understanding of the mechanisms and regulation of plastid proliferation in the shoot apex are discussed.}, } @article {pmid29917238, year = {2018}, author = {Petrosky, AL}, title = {Digest: Extra-pair mating and inbreeding avoidance in a socially monogamous fairy-wren.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13526}, pmid = {29917238}, issn = {1558-5646}, abstract = {Infidelity in socially monogamous birds may be a mechanism of inbreeding avoidance and may be impacted by cooperative breeding. Hajduk et al. (2018) find that relatedness increases extra-pair mating only in mother-son social pairs of Malurus cyaneus, while a greater number of nest helpers consistently increases the proportion of extra-pair offspring. These findings suggest that there may be multiple explanations for extra-pair mating within a single population.}, } @article {pmid29917229, year = {2018}, author = {Schmidt, C and Garroway, CJ}, title = {Digest: Local adaptation at close quarters.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13521}, pmid = {29917229}, issn = {1558-5646}, abstract = {Although the theory of how gene flow and genetic drift interact with local adaptation is well understood, few empirical studies have examined this process. Hämälä et al. (2018) present evidence that adaptive divergence between populations of Arabidopsis lyrata can persist in the face of relatively high levels of gene flow and drift. Maintaining divergence despite gene flow and drift has important implications for understanding adaptive responses of populations in response to human-driven environmental change.}, } @article {pmid29917223, year = {2018}, author = {Randle, AM and Spigler, RB and Kalisz, S}, title = {Shifts to earlier selfing in sympatry may reduce costs of pollinator sharing.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13522}, pmid = {29917223}, issn = {1558-5646}, abstract = {Coexisting plant congeners often experience strong competition for resources. Competition for pollinators can result in direct fitness costs via reduced seed set or indirect costs via heterospecific pollen transfer (HPT), causing subsequent gamete loss and unfit hybrid offspring production. Autonomous selfing may alleviate these costs, but to preempt HPT, selfing should occur early, before opportunities for HPT occur (i.e., "preemptive selfing hypothesis"). We evaluated conditions for this hypothesis in Collinsia sister species, C. linearis and C. rattanii. In field studies, we found virtually identical flowering times and pollinator sharing between congeners in sympatric populations. Compared to allopatric populations, sympatric C. linearis populations enjoyed higher pollinator visitation rates, whereas visitation to C. rattanii did not differ in sympatry. Importantly, the risk of HPT to each species in sympatry was strongly asymmetrical; interspecies visits comprised 40% of all flower-to-flower visits involving C. rattanii compared to just 4% involving C. linearis. Additionally, our greenhouse experiment demonstrated a strong cost of hybridization when C. rattanii was the pollen donor. Together, these results suggest that C. rattanii pays the greatest cost of pollinator sharing. Matching predictions of the preemptive selfing hypothesis, C. rattanii exhibit significantly earlier selfing in sympatric relative to allopatric populations.}, } @article {pmid29917220, year = {2018}, author = {Greer, J}, title = {Digest: The honesty of aposematic coloration in the six-spot burnet moth.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13525}, pmid = {29917220}, issn = {1558-5646}, } @article {pmid29916801, year = {2018}, author = {Kaewwichian, R and Khunnamwong, P and Jindamorakot, S and Lertwattanasakul, N and Limtong, S}, title = {Cryptotrichosporon siamense sp. nov., a ballistoconidium-forming yeast species in Trichosporonales isolated in Thailand.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2473-2477}, doi = {10.1099/ijsem.0.002858}, pmid = {29916801}, issn = {1466-5034}, mesh = {Basidiomycota/*classification/genetics/isolation & purification ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Ferns/*microbiology ; Mycological Typing Techniques ; *Phylogeny ; Pigmentation ; Plant Leaves/*microbiology ; Sequence Analysis, DNA ; Soil ; Spores, Fungal ; Thailand ; }, abstract = {Two strains, which formed pink colonies and produced ballistoconidia and represented a novel anamorphic yeast species, were isolated from peat (DMKU-SPS1-2) and fern leaf (ST-145) collected in Thailand. Analysis of the sequences of the D1/D2 domains of the large subunit (LSU) rRNA gene and the internal transcribed spacer (ITS) regions showed that the two strains were identical to the sequences of the D1/D2 domains of the LSU rRNA gene and differed by two nucleotide substitutions in the ITS regions. Phylogenetic analysis based on the combined sequences of the ITS and the D1/D2 regions confirmed that the two strains represented a single species in the genus Cryptotrichosporon that was distinct from the other known species of the genus. Cryptotrichosporon argae (CBS 14376T) was the most closely related species, but with 2.2 % nucleotide substitutions in the D1/D2 domains of the LSU rRNA gene, and 6.8-8.0 % nucleotide substitutions in the ITS regions. Therefore, the two strains were assigned as a novel species, for which we propose the name Cryptotrichosporon siamense sp. nov. The type is DMKU-SPS1-2T. The MycoBank number of the novel species is MB82336.}, } @article {pmid29916800, year = {2018}, author = {Khumalo, ZTH and Brayton, KA and Collins, NE and Chaisi, ME and Quan, M and Oosthuizen, MC}, title = {Evidence confirming the phylogenetic position of Anaplasma centrale (ex Theiler 1911) Ristic and Kreier 1984.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2682-2691}, doi = {10.1099/ijsem.0.002832}, pmid = {29916800}, issn = {1466-5034}, mesh = {Amino Acid Sequence ; Anaplasma centrale/*classification ; Anaplasma marginale ; Anaplasmosis/*microbiology ; Animals ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Israel ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Ruminants/*microbiology ; Sequence Analysis, DNA ; South Africa ; }, abstract = {In 1911, Sir Arnold Theiler isolated and described a parasite that was very similar to Anaplasma marginale but which was more centrally located within the erythrocytes of the host cells, and was much less pathogenic than A. marginale. He named the parasite A. marginale variety centrale. The name Anaplasma centrale, referring to the same organism, was published in Validation List No. 15 in 1984, but the publication was based on an erroneous assumption that Theiler had indicated that it was a separate species. Many authors have subsequently accepted this organism as a separate species, but evidence to indicate that it is a distinct species has never been presented. The near full-length 16S rRNA gene sequence, and the deduced amino acid sequences for groEL and msp4 from several isolates of A. marginale and A. centrale from around South Africa were compared with those of the A. marginale type strain, St Maries, and the A. centrale Israel strain and other reference sequences. Phylogenetic analyses of these sequences demonstrated that A. centrale consistently forms a separate clade from A. marginale, supported by high bootstrap values (≥90 %), revealing that there is divergence between these two organisms. In addition, we discuss distinctive characteristics which have been published recently, such as differences in Msp1a/Msp1aS gene structure, as well as genome architecture that provide further evidence to suggest that A. centrale is, in fact, a separate species. Our results, therefore, provide evidence to support the existing nomenclature, and confirm that A. centrale (ex Theiler 1911) Ristic and Kreier 1984 is, indeed, a distinct species.}, } @article {pmid29916796, year = {2018}, author = {Guu, JR and Wang, LT and Hamada, M and Wang, C and Lin, RW and Huang, L and Watanabe, K}, title = {Lactobacillus bambusae sp. nov., isolated from traditional fermented ma bamboo shoots in Taiwan.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2424-2430}, doi = {10.1099/ijsem.0.002837}, pmid = {29916796}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fermentation ; Fermented Foods/*microbiology ; *Food Microbiology ; Genes, Bacterial ; Lactobacillus/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Taiwan ; Vegetables/*microbiology ; }, abstract = {A Gram-stain-positive strain, BS-W1T, was isolated from a traditional fermented ma bamboo shoots (Dendrocalamus latiflorus Munro) product of Taiwan. It was rod-shaped, non-motile, non-haemolytic, asporogenous, facultatively anaerobic, heterofermentative and did not exhibit catalase or oxidase activities. Comparative analysis of 16S rRNA, pheS, rpoA and gyrB gene sequences demonstrated that the novel strain BS-W1T was a member of the genus Lactobacillus. On the basis of 16S RNA gene sequence similarity, the type strains of Lactobacillus oryzae (94.4 % similarity), Lactobacillus acidifarinae (93.8 %), Lactobacillus namurensis (93.7 %) and Lactobacillus zymae (93.7 %) were the closest neighbours to strain BS-W1T. The pheS, rpoA and gyrB gene sequence similarities of strain BS-W1T to closely related these species were less than 80.2 %. DNA-DNA reassociation values with these type strains were 21.0-33.8 %. The DNA G+C content was 46.6 mol%. The average nucleotide identity values between BS-W1T and the closest relatives were lower than 70 %. Phenotypic and genotypic features demonstrated that the strain represents a novel species of the genus Lactobacillus, for which the name Lactobacillus bambusae sp. nov. is proposed. The type strain is BS-W1T (=BCRC 80970T=NBRC 112377T).}, } @article {pmid29916795, year = {2018}, author = {Kim, JY and Kim, DU and Kang, MS and Jang, JH and Kim, SJ and Kim, MJ and Lee, JY and Lee, YS and Zhang, J and Lim, S and Kim, MK}, title = {Roseomonas radiodurans sp. nov., a gamma-radiation-resistant bacterium isolated from gamma ray-irradiated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2443-2447}, doi = {10.1099/ijsem.0.002852}, pmid = {29916795}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Gamma Rays ; Methylobacteriaceae/*classification/isolation & purification/radiation effects ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Radiation Tolerance ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A bacterial strain, designated 17Sr1-1T, was isolated from gamma ray-irradiated soil. Cells of this strain were Gram-stain-negative, strictly aerobic, motile and non-spore-forming rods. Growth occurred at 18-42 ˚C and pH 6.0-8.0, but no growth occurred at 2 % NaCl concentration. The major fatty acids of strain 17Sr1-1T were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), iso-C17 : 1ω5c and C16 : 0. The polar lipid profile contained diphosphatidylglycerol, glycolipid, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and four unidentified lipids. The G+C content of the genomic DNA of 17Sr1-1T was 71.9 mol%. The 16S rRNA gene sequence analysis showed that strain 17Sr1-1T was phylogenetically related to Roseomonas pecuniae N75T and Roseomonas rosea 173-96T (96.6 and 96.3 % sequence similarity, respectively). The genotypic and phenotypic data showed that strain 17Sr1-1T could be distinguished from its phylogenetically related species, and that this strain represented a novel species within the genus Roseomonas, for which the name Roseomonas radiodurans sp. nov. (type strain 17Sr1-1T=KCTC 52899T=NBRC 112872T) is proposed as the first reported gamma ray-resistant Roseomonas species.}, } @article {pmid29916034, year = {2018}, author = {Tarrah, A and Treu, L and Giaretta, S and Duarte, V and Corich, V and Giacomini, A}, title = {Differences in Carbohydrates Utilization and Antibiotic Resistance Between Streptococcus macedonicus and Streptococcus thermophilus Strains Isolated from Dairy Products in Italy.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29916034}, issn = {1432-0991}, support = {60A08-5771/11//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; 60A08-0032/11//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, abstract = {Streptococcus thermophilus and S. macedonicus are the only two species of the genus related to food productions so far known. In the present study, eight S. thermophilus and seven S. macedonicus strains isolated from dairy environments in Italy were compared in order to evidence possible species-specific technological characteristics. Their capability to use lactose, galactose, fructose, and glucose, sugars commonly present in foods and two carbohydrates considered as prebiotics, xylose and inulin, along with the respective growth kinetics were studied. Results showed a luxuriant growth on lactose and different behaviors on galactose, glucose, and fructose. No growth on inulin and xylose was recorded, which is a positive feature for strains intended to be used as starter cultures. Growth parameters, namely, λ, µmax, and Nmax, were estimated by using the Gompertz model. Antibiotic resistance to 14 drugs revealed an overall similar behavior between the two species with only a marked difference regarding gentamycin. Antimicrobial activity was also tested against six deleterious bacterial strains, but none of the strains evidenced inhibitory capabilities. The results presented here could be helpful to compare technological potentialities of the two species and to choose strains of the most suitable species for selected microbiological food transformations.}, } @article {pmid29915430, year = {2018}, author = {Wu, L and Shi, W and Long, J and Guo, X and Michailidou, K and Beesley, J and Bolla, MK and Shu, XO and Lu, Y and Cai, Q and Al-Ejeh, F and Rozali, E and Wang, Q and Dennis, J and Li, B and Zeng, C and Feng, H and Gusev, A and Barfield, RT and Andrulis, IL and Anton-Culver, H and Arndt, V and Aronson, KJ and Auer, PL and Barrdahl, M and Baynes, C and Beckmann, MW and Benitez, J and Bermisheva, M and Blomqvist, C and Bogdanova, NV and Bojesen, SE and Brauch, H and Brenner, H and Brinton, L and Broberg, P and Brucker, SY and Burwinkel, B and Caldés, T and Canzian, F and Carter, BD and Castelao, JE and Chang-Claude, J and Chen, X and Cheng, TD and Christiansen, H and Clarke, CL and , and Collée, M and Cornelissen, S and Couch, FJ and Cox, D and Cox, A and Cross, SS and Cunningham, JM and Czene, K and Daly, MB and Devilee, P and Doheny, KF and Dörk, T and Dos-Santos-Silva, I and Dumont, M and Dwek, M and Eccles, DM and Eilber, U and Eliassen, AH and Engel, C and Eriksson, M and Fachal, L and Fasching, PA and Figueroa, J and Flesch-Janys, D and Fletcher, O and Flyger, H and Fritschi, L and Gabrielson, M and Gago-Dominguez, M and Gapstur, SM and García-Closas, M and Gaudet, MM and Ghoussaini, M and Giles, GG and Goldberg, MS and Goldgar, DE and González-Neira, A and Guénel, P and Hahnen, E and Haiman, CA and Håkansson, N and Hall, P and Hallberg, E and Hamann, U and Harrington, P and Hein, A and Hicks, B and Hillemanns, P and Hollestelle, A and Hoover, RN and Hopper, JL and Huang, G and Humphreys, K and Hunter, DJ and Jakubowska, A and Janni, W and John, EM and Johnson, N and Jones, K and Jones, ME and Jung, A and Kaaks, R and Kerin, MJ and Khusnutdinova, E and Kosma, VM and Kristensen, VN and Lambrechts, D and Le Marchand, L and Li, J and Lindström, S and Lissowska, J and Lo, WY and Loibl, S and Lubinski, J and Luccarini, C and Lux, MP and MacInnis, RJ and Maishman, T and Kostovska, IM and Mannermaa, A and Manson, JE and Margolin, S and Mavroudis, D and Meijers-Heijboer, H and Meindl, A and Menon, U and Meyer, J and Mulligan, AM and Neuhausen, SL and Nevanlinna, H and Neven, P and Nielsen, SF and Nordestgaard, BG and Olopade, OI and Olson, JE and Olsson, H and Peterlongo, P and Peto, J and Plaseska-Karanfilska, D and Prentice, R and Presneau, N and Pylkäs, K and Rack, B and Radice, P and Rahman, N and Rennert, G and Rennert, HS and Rhenius, V and Romero, A and Romm, J and Rudolph, A and Saloustros, E and Sandler, DP and Sawyer, EJ and Schmidt, MK and Schmutzler, RK and Schneeweiss, A and Scott, RJ and Scott, CG and Seal, S and Shah, M and Shrubsole, MJ and Smeets, A and Southey, MC and Spinelli, JJ and Stone, J and Surowy, H and Swerdlow, AJ and Tamimi, RM and Tapper, W and Taylor, JA and Terry, MB and Tessier, DC and Thomas, A and Thöne, K and Tollenaar, RAEM and Torres, D and Truong, T and Untch, M and Vachon, C and Van Den Berg, D and Vincent, D and Waisfisz, Q and Weinberg, CR and Wendt, C and Whittemore, AS and Wildiers, H and Willett, WC and Winqvist, R and Wolk, A and Xia, L and Yang, XR and Ziogas, A and Ziv, E and , and Dunning, AM and Pharoah, PDP and Simard, J and Milne, RL and Edwards, SL and Kraft, P and Easton, DF and Chenevix-Trench, G and Zheng, W}, title = {A transcriptome-wide association study of 229,000 women identifies new candidate susceptibility genes for breast cancer.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {968-978}, doi = {10.1038/s41588-018-0132-x}, pmid = {29915430}, issn = {1546-1718}, support = {R25 CA160056/CA/NCI NIH HHS/United States ; P50 CA116201/CA/NCI NIH HHS/United States ; U19 CA148065/CA/NCI NIH HHS/United States ; R01 CA158473/CA/NCI NIH HHS/United States ; K99 CA218892/CA/NCI NIH HHS/United States ; }, abstract = {The breast cancer risk variants identified in genome-wide association studies explain only a small fraction of the familial relative risk, and the genes responsible for these associations remain largely unknown. To identify novel risk loci and likely causal genes, we performed a transcriptome-wide association study evaluating associations of genetically predicted gene expression with breast cancer risk in 122,977 cases and 105,974 controls of European ancestry. We used data from the Genotype-Tissue Expression Project to establish genetic models to predict gene expression in breast tissue and evaluated model performance using data from The Cancer Genome Atlas. Of the 8,597 genes evaluated, significant associations were identified for 48 at a Bonferroni-corrected threshold of P < 5.82 × 10-6, including 14 genes at loci not yet reported for breast cancer. We silenced 13 genes and showed an effect for 11 on cell proliferation and/or colony-forming efficiency. Our study provides new insights into breast cancer genetics and biology.}, } @article {pmid29915429, year = {2018}, author = {Sibbesen, JA and Maretty, L and , and Krogh, A}, title = {Accurate genotyping across variant classes and lengths using variant graphs.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {1054-1059}, doi = {10.1038/s41588-018-0145-5}, pmid = {29915429}, issn = {1546-1718}, abstract = {Genotype estimates from short-read sequencing data are typically based on the alignment of reads to a linear reference, but reads originating from more complex variants (for example, structural variants) often align poorly, resulting in biased genotype estimates. This bias can be mitigated by first collecting a set of candidate variants across discovery methods, individuals and databases, and then realigning the reads to the variants and reference simultaneously. However, this realignment problem has proved computationally difficult. Here, we present a new method (BayesTyper) that uses exact alignment of read k-mers to a graph representation of the reference and variants to efficiently perform unbiased, probabilistic genotyping across the variation spectrum. We demonstrate that BayesTyper generally provides superior variant sensitivity and genotyping accuracy relative to existing methods when used to integrate variants across discovery approaches and individuals. Finally, we demonstrate that including a 'variation-prior' database containing already known variants significantly improves sensitivity.}, } @article {pmid29915428, year = {2018}, author = {Alvarez, MJ and Subramaniam, PS and Tang, LH and Grunn, A and Aburi, M and Rieckhof, G and Komissarova, EV and Hagan, EA and Bodei, L and Clemons, PA and Dela Cruz, FS and Dhall, D and Diolaiti, D and Fraker, DA and Ghavami, A and Kaemmerer, D and Karan, C and Kidd, M and Kim, KM and Kim, HC and Kunju, LP and Langel, Ü and Li, Z and Lee, J and Li, H and LiVolsi, V and Pfragner, R and Rainey, AR and Realubit, RB and Remotti, H and Regberg, J and Roses, R and Rustgi, A and Sepulveda, AR and Serra, S and Shi, C and Yuan, X and Barberis, M and Bergamaschi, R and Chinnaiyan, AM and Detre, T and Ezzat, S and Frilling, A and Hommann, M and Jaeger, D and Kim, MK and Knudsen, BS and Kung, AL and Leahy, E and Metz, DC and Milsom, JW and Park, YS and Reidy-Lagunes, D and Schreiber, S and Washington, K and Wiedenmann, B and Modlin, I and Califano, A}, title = {A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {979-989}, doi = {10.1038/s41588-018-0138-4}, pmid = {29915428}, issn = {1546-1718}, abstract = {We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.}, } @article {pmid29915422, year = {2018}, author = {Gewin, V}, title = {A deforestation detective rethinks how industry can quell emissions.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {477}, doi = {10.1038/d41586-018-05450-0}, pmid = {29915422}, issn = {1476-4687}, } @article {pmid29915421, year = {2018}, author = {Rosen, J}, title = {How a hobby can boost researchers' productivity and creativity.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {475-477}, doi = {10.1038/d41586-018-05449-7}, pmid = {29915421}, issn = {1476-4687}, } @article {pmid29915345, year = {2018}, author = {Ser-Giacomi, E and Zinger, L and Malviya, S and De Vargas, C and Karsenti, E and Bowler, C and De Monte, S}, title = {Ubiquitous abundance distribution of non-dominant plankton across the global ocean.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1243-1249}, doi = {10.1038/s41559-018-0587-2}, pmid = {29915345}, issn = {2397-334X}, abstract = {Marine plankton populate 70% of Earth's surface, providing the energy that fuels ocean food webs and contributing to global biogeochemical cycles. Plankton communities are extremely diverse and geographically variable, and are overwhelmingly composed of low-abundance species. The role of this rare biosphere and its ecological underpinnings are however still unclear. Here, we analyse the extensive dataset generated by the Tara Oceans expedition for marine microbial eukaryotes (protists) and use an adaptive algorithm to explore how metabarcoding-based abundance distributions vary across plankton communities in the global ocean. We show that the decay in abundance of non-dominant operational taxonomic units, which comprise over 99% of local richness, is commonly governed by a power-law. Despite the high spatial turnover in species composition, the power-law exponent varies by less than 10% across locations and shows no biogeographical signature, but is weakly modulated by cell size. Such striking regularity suggests that the assembly of plankton communities in the dynamic and highly variable ocean environment is governed by large-scale ubiquitous processes. Understanding their origin and impact on plankton ecology will be important for evaluating the resilience of marine biodiversity in a changing ocean.}, } @article {pmid29915344, year = {2018}, author = {McEntee, JP and Tobias, JA and Sheard, C and Burleigh, JG}, title = {Tempo and timing of ecological trait divergence in bird speciation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1120-1127}, doi = {10.1038/s41559-018-0570-y}, pmid = {29915344}, issn = {2397-334X}, abstract = {Organismal traits may evolve either gradually or in rapid pulses, but the relative importance of these modes in the generation of species differences is unclear. Additionally, while pulsed evolution is frequently assumed to be associated with speciation events, few studies have explicitly examined how the tempo of trait divergence varies with respect to different geographical phases of speciation, starting with geographic isolation and ending, in many cases, with spatial overlap (sympatry). Here we address these issues by combining divergence time estimates, trait measurements and geographic range data for 952 avian sister species pairs worldwide to examine the tempo and timing of trait divergence in recent speciation events. We show that patterns of divergence in key ecological traits are not gradual, but instead seem to follow a pattern of relative stasis interspersed with evolutionary pulses of varying magnitude. We also find evidence that evolutionary pulses generally precede sympatry, and that greater trait disparity is associated with sympatry. These findings suggest that early pulses of trait divergence promote subsequent transitions to sympatry, rather than occurring after sympatry has been established. Incorporating models with evolutionary pulses of varying magnitude into speciation theory may explain why some species pairs achieve rapid sympatry whereas others undergo prolonged geographical exclusion.}, } @article {pmid29915343, year = {2018}, author = {Pigot, AL and Jetz, W and Sheard, C and Tobias, JA}, title = {The macroecological dynamics of species coexistence in birds.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1112-1119}, doi = {10.1038/s41559-018-0572-9}, pmid = {29915343}, issn = {2397-334X}, abstract = {Ecological communities are assembled from the overlapping of species in geographic space, but the mechanisms facilitating or limiting such overlaps are difficult to resolve. Here, we combine phylogenetic, morphological and environmental data to model how multiple processes regulate the origin and maintenance of geographic range overlap across 1,115 pairs of avian sister species globally. We show that coexistence cannot be adequately predicted by either dispersal-assembly (that is, biogeographic) models or niche-assembly models alone. Instead, our results overwhelmingly support an integrated model with different assembly processes dominating at different stages of coexistence. The initial attainment of narrow geographic overlap is dictated by intrinsic dispersal ability and the time available for dispersal, whereas wider coexistence is largely dependent on niche availability, increasing with ecosystem productivity and divergence in niche-related traits, and apparently declining as communities become saturated with species. Furthermore, although coexistence of any individual pair of species is highly stochastic, we find that integrating assembly processes allows broad variation in the incidence and extent of coexistence to be predicted with reasonable accuracy. Our findings demonstrate how phylogenetic data coupled with environmental factors and functional traits can begin to clarify the multi-layered processes shaping the distribution of biodiversity at large spatial scales.}, } @article {pmid29915342, year = {2018}, author = {Shaver, EC and Burkepile, DE and Silliman, BR}, title = {Local management actions can increase coral resilience to thermally-induced bleaching.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1075-1079}, doi = {10.1038/s41559-018-0589-0}, pmid = {29915342}, issn = {2397-334X}, abstract = {Recent large-scale analyses suggest that local management actions may not protect coral reefs from climate change, yet most local threat-reduction strategies have not been tested experimentally. We show that removing coral predators is a common local action used by managers across the world, and that removing the corallivorous snail Coralliophila abbreviata from Caribbean brain corals (Pseudodiploria and Diploria species) before a major warming event increased coral resilience by reducing bleaching severity (resistance) and post-bleaching tissue mortality (recovery). Our results highlight the need for increased evaluation and identification of local interventions that improve coral reef resilience.}, } @article {pmid29915341, year = {2018}, author = {Ramakers, JJC and Culina, A and Visser, ME and Gienapp, P}, title = {Environmental coupling of heritability and selection is rare and of minor evolutionary significance in wild populations.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1093-1103}, pmid = {29915341}, issn = {2397-334X}, abstract = {Predicting the rate of adaptation to environmental change in wild populations is important for understanding evolutionary change. However, predictions may be unreliable if the two key variables affecting the rate of evolutionary change-heritability and selection-are both affected by the same environmental variable. To determine how general such an environmentally induced coupling of heritability and selection is, and how this may influence the rate of adaptation, we made use of freely accessible, open data on pedigreed wild populations to answer this question at the broadest possible scale. Using 16 populations from 10 vertebrate species, which provided data on 50 traits (relating to body mass, morphology, physiology, behaviour and life history), we found evidence for an environmentally induced relationship between heritability and selection in only 6 cases, with weak evidence that this resulted in an increase or decrease in the expected selection response. We conclude that such a coupling of heritability and selection is unlikely to strongly affect evolutionary change, even though both heritability and selection are commonly postulated to be dependent on the environment.}, } @article {pmid29915340, year = {2018}, author = {Maron, M and Simmonds, JS and Watson, JEM}, title = {Bold nature retention targets are essential for the global environment agenda.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1194-1195}, doi = {10.1038/s41559-018-0595-2}, pmid = {29915340}, issn = {2397-334X}, } @article {pmid29915339, year = {2018}, author = {Culina, A and Crowther, TW and Ramakers, JJC and Gienapp, P and Visser, ME}, title = {How to do meta-analysis of open datasets.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1053-1056}, doi = {10.1038/s41559-018-0579-2}, pmid = {29915339}, issn = {2397-334X}, } @article {pmid29915312, year = {2018}, author = {Shi, H and Herron, AN and Shao, Y and Shao, Q and Yu, JQ}, title = {Enantioselective remote meta-C-H arylation and alkylation via a chiral transient mediator.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {581-585}, pmid = {29915312}, issn = {1476-4687}, support = {R01 GM102265/GM/NIGMS NIH HHS/United States ; }, mesh = {Alkylation ; Benzylamines/chemistry ; Carbon/*chemistry ; Catalysis ; Hydrogen/*chemistry ; Norbornanes/chemistry ; Stereoisomerism ; }, abstract = {Enantioselective carbon-hydrogen (C-H) activation reactions by asymmetric metallation could provide new routes for the construction of chiral molecules1,2. However, current methods are typically limited to the formation of five- or six-membered metallacycles, thereby preventing the asymmetric functionalization of C-H bonds at positions remote to existing functional groups. Here we report enantioselective remote C-H activation using a catalytic amount of a chiral norbornene as a transient mediator, which relays initial ortho-C-H activation to the meta position. This was used in the enantioselective meta-C-H arylation of benzylamines, as well as the arylation and alkylation of homobenzylamines. The enantioselectivities obtained using the chiral transient mediator are comparable across different classes of substrates containing either neutral σ-donor or anionic coordinating groups. This relay strategy could provide an alternative means to remote chiral induction, one of the most challenging problems in asymmetric catalysis3,4.}, } @article {pmid29915204, year = {2018}, author = {Rivett, DW and Bell, T}, title = {Abundance determines the functional role of bacterial phylotypes in complex communities.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {767-772}, pmid = {29915204}, issn = {2058-5276}, support = {311399//European Research Council/International ; }, abstract = {Bacterial communities are essential for the functioning of the Earth's ecosystems 1 . A key challenge is to quantify the functional roles of bacterial taxa in nature to understand how the properties of ecosystems change over time or under different environmental conditions 2 . Such knowledge could be used, for example, to understand how bacteria modulate biogeochemical cycles 3 , and to engineer bacterial communities to optimize desirable functional processes 4 . Communities of bacteria are, however, extraordinarily complex with hundreds of interacting taxa in every gram of soil and every millilitre of pond water 5 . Little is known about how the tangled interactions within natural bacterial communities mediate ecosystem functioning, but high levels of bacterial diversity have led to the assumption that many taxa are functionally redundant 6 . Here, we pinpoint the bacterial taxa associated with keystone functional roles, and show that rare and common bacteria are implicated in fundamentally different types of ecosystem functioning. By growing hundreds of bacterial communities collected from a natural aquatic environment (rainwater-filled tree holes) under the same environmental conditions, we show that negative statistical interactions among abundant phylotypes drive variation in broad functional measures (respiration, metabolic potential, cell yield), whereas positive interactions between rare phylotypes influence narrow functional measures (the capacity of the communities to degrade specific substrates). The results alter our understanding of bacterial ecology by demonstrating that unique components of complex communities are associated with different types of ecosystem functioning.}, } @article {pmid29915092, year = {2018}, author = {Xu, P and Huang, T and Huang, J and Yan, Y and Mallouk, TE}, title = {Dye-sensitized photoelectrochemical water oxidation through a buried junction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6946-6951}, pmid = {29915092}, issn = {1091-6490}, abstract = {Water oxidation has long been a challenge in artificial photosynthetic devices that convert solar energy into fuels. Water-splitting dye-sensitized photoelectrochemical cells (WS-DSPECs) provide a modular approach for integrating light-harvesting molecules with water-oxidation catalysts on metal-oxide electrodes. Despite recent progress in improving the efficiency of these devices by introducing good molecular water-oxidation catalysts, WS-DSPECs have poor stability, owing to the oxidation of molecular components at very positive electrode potentials. Here we demonstrate that a solid-state dye-sensitized solar cell (ss-DSSC) can be used as a buried junction for stable photoelectrochemical water splitting. A thin protecting layer of TiO2 grown by atomic layer deposition (ALD) stabilizes the operation of the photoanode in aqueous solution, although as a solar cell there is a performance loss due to increased series resistance after the coating. With an electrodeposited iridium oxide layer, a photocurrent density of 1.43 mA cm-2 was observed in 0.1 M pH 6.7 phosphate solution at 1.23 V versus reversible hydrogen electrode, with good stability over 1 h. We measured an incident photon-to-current efficiency of 22% at 540 nm and a Faradaic efficiency of 43% for oxygen evolution. While the potential profile of the catalyst layer suggested otherwise, we confirmed the formation of a buried junction in the as-prepared photoelectrode. The buried junction design of ss-DSSs adds to our understanding of semiconductor-electrocatalyst junction behaviors in the presence of a poor semiconducting material.}, } @article {pmid29915091, year = {2018}, author = {Schiebelhut, LM and Puritz, JB and Dawson, MN}, title = {Decimation by sea star wasting disease and rapid genetic change in a keystone species, Pisaster ochraceus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7069-7074}, pmid = {29915091}, issn = {1091-6490}, mesh = {*Alleles ; Animals ; *Gene Frequency ; Starfish/*genetics ; Wasting Syndrome/*genetics/*veterinary ; }, abstract = {Standing genetic variation enables or restricts a population's capacity to respond to changing conditions, including the extreme disturbances expected to increase in frequency and intensity with continuing anthropogenic climate change. However, we know little about how populations might respond to extreme events with rapid genetic shifts, or how population dynamics may influence and be influenced by population genomic change. We use a range-wide epizootic, sea star wasting disease, that onset in mid-2013 and caused mass mortality in Pisaster ochraceus to explore how a keystone marine species responded to an extreme perturbation. We integrated field surveys with restriction site-associated DNA sequencing data to (i) describe the population dynamics of mortality and recovery, and (ii) compare allele frequencies in mature P. ochraceus before the disease outbreak with allele frequencies in adults and new juveniles after the outbreak, to identify whether selection may have occurred. We found P. ochraceus suffered 81% mortality in the study region between 2012 and 2015, and experienced a concurrent 74-fold increase in recruitment beginning in late 2013. Comparison of pre- and postoutbreak adults revealed significant allele frequency changes at three loci, which showed consistent changes across the large majority of locations. Allele frequency shifts in juvenile P. ochraceus (spawned from premortality adults) were consistent with those seen in adult survivors. Such parallel shifts suggest detectable signals of selection and highlight the potential for persistence of this change in subsequent generations, which may influence the resilience of this keystone species to future outbreaks.}, } @article {pmid29915090, year = {2018}, author = {Liang, K and Li, N and Wang, X and Dai, J and Liu, P and Wang, C and Chen, XW and Gao, N and Xiao, J}, title = {Cryo-EM structure of human mitochondrial trifunctional protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7039-7044}, pmid = {29915090}, issn = {1091-6490}, mesh = {*Cryoelectron Microscopy ; Humans ; Mitochondrial Trifunctional Protein/metabolism/*ultrastructure ; Protein Structure, Quaternary ; Protein Structure, Secondary ; }, abstract = {The mitochondrial trifunctional protein (TFP) catalyzes three reactions in the fatty acid β-oxidation process. Mutations in the two TFP subunits cause mitochondrial trifunctional protein deficiency and acute fatty liver of pregnancy that can lead to death. Here we report a 4.2-Å cryo-electron microscopy α2β2 tetrameric structure of the human TFP. The tetramer has a V-shaped architecture that displays a distinct assembly compared with the bacterial TFPs. A concave surface of the TFP tetramer interacts with the detergent molecules in the structure, suggesting that this region is involved in associating with the membrane. Deletion of a helical hairpin in TFPβ decreases its binding to the liposomes in vitro and reduces its membrane targeting in cells. Our results provide the structural basis for TFP function and have important implications for fatty acid oxidation related diseases.}, } @article {pmid29915089, year = {2018}, author = {Chen, S and Cui, Y and Parashar, S and Novick, PJ and Ferro-Novick, S}, title = {ER-phagy requires Lnp1, a protein that stabilizes rearrangements of the ER network.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6237-E6244}, pmid = {29915089}, issn = {1091-6490}, support = {R01 GM035370/GM/NIGMS NIH HHS/United States ; R01 GM082861/GM/NIGMS NIH HHS/United States ; R01 GM115422/GM/NIGMS NIH HHS/United States ; }, mesh = {Autophagosomes/*metabolism ; Autophagy-Related Proteins/genetics/metabolism ; Bridged Bicyclo Compounds, Heterocyclic/pharmacology ; Endoplasmic Reticulum/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Thiazolidines/pharmacology ; Vesicular Transport Proteins/genetics/metabolism ; }, abstract = {The endoplasmic reticulum (ER) forms a contiguous network of tubules and sheets that is predominantly associated with the cell cortex in yeast. Upon treatment with rapamycin, the ER undergoes degradation by selective autophagy. This process, termed ER-phagy, requires Atg40, a selective autophagy receptor that localizes to the cortical ER. Here we report that ER-phagy also requires Lnp1, an ER membrane protein that normally resides at the three-way junctions of the ER network, where it serves to stabilize the network as it is continually remodeled. Rapamycin treatment increases the expression of Atg40, driving ER domains marked by Atg40 puncta to associate with Atg11, a scaffold protein needed to form autophagosomes. Although Atg40 largely localizes to the cortical ER, the autophagy machinery resides in the cell interior. The localization of Atg40 to sites of autophagosome formation is blocked in an lnp1Δ mutant or upon treatment of wild-type cells with the actin-depolymerizing drug Latrunculin A. This prevents the association of Atg40 with Atg11 and the packaging of the ER into autophagosomes. We propose that Lnp1 is needed to stabilize the actin-dependent remodeling of the ER that is essential for ER-phagy.}, } @article {pmid29915088, year = {2018}, author = {Floryan, D and Van Buren, T and Smits, AJ}, title = {Efficient cruising for swimming and flying animals is dictated by fluid drag.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {32}, pages = {8116-8118}, pmid = {29915088}, issn = {1091-6490}, mesh = {Animals ; Biomechanical Phenomena ; Birds/physiology ; Chiroptera/physiology ; Dolphins/physiology ; Fishes/physiology ; Flight, Animal/*physiology ; Insecta/physiology ; Locomotion/*physiology ; Models, Biological ; Sharks/physiology ; Swimming/*physiology ; Wings, Animal/*physiology ; }, abstract = {Many swimming and flying animals are observed to cruise in a narrow range of Strouhal numbers, where the Strouhal number [Formula: see text] is a dimensionless parameter that relates stroke frequency f, amplitude A, and forward speed U. Dolphins, sharks, bony fish, birds, bats, and insects typically cruise in the range [Formula: see text], which coincides with the Strouhal number range for maximum efficiency as found by experiments on heaving and pitching airfoils. It has therefore been postulated that natural selection has tuned animals to use this range of Strouhal numbers because it confers high efficiency, but the reason why this is so is still unclear. Here, by using simple scaling arguments, we argue that the Strouhal number for peak efficiency is largely determined by fluid drag on the fins and wings.}, } @article {pmid29915087, year = {2018}, author = {Nicolas, D and Zoller, B and Suter, DM and Naef, F}, title = {Modulation of transcriptional burst frequency by histone acetylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7153-7158}, pmid = {29915087}, issn = {1091-6490}, mesh = {ARNTL Transcription Factors/*biosynthesis/genetics ; Acetylation ; Animals ; Circadian Rhythm/*physiology ; Gene Expression Regulation/*physiology ; Histones/*metabolism ; Mice ; *Models, Biological ; NIH 3T3 Cells ; Promoter Regions, Genetic/*physiology ; Transcription, Genetic/*physiology ; }, abstract = {Many mammalian genes are transcribed during short bursts of variable frequencies and sizes that substantially contribute to cell-to-cell variability. However, which molecular mechanisms determine bursting properties remains unclear. To probe putative mechanisms, we combined temporal analysis of transcription along the circadian cycle with multiple genomic reporter integrations, using both short-lived luciferase live microscopy and single-molecule RNA-FISH. Using the Bmal1 circadian promoter as our model, we observed that rhythmic transcription resulted predominantly from variations in burst frequency, while the genomic position changed the burst size. Thus, burst frequency and size independently modulated Bmal1 transcription. We then found that promoter histone-acetylation level covaried with burst frequency, being greatest at peak expression and lowest at trough expression, while remaining unaffected by the genomic location. In addition, specific deletions of ROR-responsive elements led to constitutively elevated histone acetylation and burst frequency. We then investigated the suggested link between histone acetylation and burst frequency by dCas9p300-targeted modulation of histone acetylation, revealing that acetylation levels influence burst frequency more than burst size. The correlation between acetylation levels at the promoter and burst frequency was also observed in endogenous circadian genes and in embryonic stem cell fate genes. Thus, our data suggest that histone acetylation-mediated control of transcription burst frequency is a common mechanism to control mammalian gene expression.}, } @article {pmid29915086, year = {2018}, author = {Tumen-Velasquez, M and Johnson, CW and Ahmed, A and Dominick, G and Fulk, EM and Khanna, P and Lee, SA and Schmidt, AL and Linger, JG and Eiteman, MA and Beckham, GT and Neidle, EL}, title = {Accelerating pathway evolution by increasing the gene dosage of chromosomal segments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7105-7110}, pmid = {29915086}, issn = {1091-6490}, mesh = {Bacterial Proteins/*genetics ; Chromosomes, Bacterial/*genetics ; *Evolution, Molecular ; *Gene Dosage ; *Genes, Bacterial ; Gram-Negative Bacteria/enzymology/*genetics ; }, abstract = {Experimental evolution is a critical tool in many disciplines, including metabolic engineering and synthetic biology. However, current methods rely on the chance occurrence of a key step that can dramatically accelerate evolution in natural systems, namely increased gene dosage. Our studies sought to induce the targeted amplification of chromosomal segments to facilitate rapid evolution. Since increased gene dosage confers novel phenotypes and genetic redundancy, we developed a method, Evolution by Amplification and Synthetic Biology (EASy), to create tandem arrays of chromosomal regions. In Acinetobacter baylyi, EASy was demonstrated on an important bioenergy problem, the catabolism of lignin-derived aromatic compounds. The initial focus on guaiacol (2-methoxyphenol), a common lignin degradation product, led to the discovery of Amycolatopsis genes (gcoAB) encoding a cytochrome P450 enzyme that converts guaiacol to catechol. However, chromosomal integration of gcoAB in Pseudomonas putida or A. baylyi did not enable guaiacol to be used as the sole carbon source despite catechol being a growth substrate. In ∼1,000 generations, EASy yielded alleles that in single chromosomal copy confer growth on guaiacol. Different variants emerged, including fusions between GcoA and CatA (catechol 1,2-dioxygenase). This study illustrates the power of harnessing chromosomal gene amplification to accelerate the evolution of desirable traits.}, } @article {pmid29915085, year = {2018}, author = {Karplus, VJ and Zhang, S and Almond, D}, title = {Quantifying coal power plant responses to tighter SO2 emissions standards in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7004-7009}, pmid = {29915085}, issn = {1091-6490}, abstract = {We evaluate the impact of China's new air pollution standards on sulfur dioxide (SO2) emissions by comparing newly available data from Continuous Emissions Monitoring Systems (CEMS) at coal power plants with satellite measures. First, we show that following the July 2014 deadline for implementing tighter emissions standards, stack concentrations of SO2 reported by CEMS declined by 13.9%. Second, on average the ratios of the declines of SO2 measures in the satellite data and the CEMS data are about 0.5. However, the degree of correspondence between the two data sources varies by policy stringency, with weak correspondence found in key regions facing the toughest new limits. Third, large plants achieved compliance earlier than small (typically) power and heat cogeneration plants. To achieve continued air quality improvement, our results suggest a need for increased scrutiny of emissions data quality and monitoring practices and clear long-term targets.}, } @article {pmid29915084, year = {2018}, author = {Gao, S and Flicker, F and Sankar, R and Zhao, H and Ren, Z and Rachmilowitz, B and Balachandar, S and Chou, F and Burch, KS and Wang, Z and van Wezel, J and Zeljkovic, I}, title = {Atomic-scale strain manipulation of a charge density wave.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6986-6990}, pmid = {29915084}, issn = {1091-6490}, abstract = {A charge density wave (CDW) is one of the fundamental instabilities of the Fermi surface occurring in a wide range of quantum materials. In dimensions higher than one, where Fermi surface nesting can play only a limited role, the selection of the particular wavevector and geometry of an emerging CDW should in principle be susceptible to controllable manipulation. In this work, we implement a simple method for straining materials compatible with low-temperature scanning tunneling microscopy/spectroscopy (STM/S), and use it to strain-engineer CDWs in 2H-NbSe2 Our STM/S measurements, combined with theory, reveal how small strain-induced changes in the electronic band structure and phonon dispersion lead to dramatic changes in the CDW ordering wavevector and geometry. Our work unveils the microscopic mechanism of a CDW formation in this system, and can serve as a general tool compatible with a range of spectroscopic techniques to engineer electronic states in any material where local strain or lattice symmetry breaking plays a role.}, } @article {pmid29915083, year = {2018}, author = {Gopal, RK and Calvo, SE and Shih, AR and Chaves, FL and McGuone, D and Mick, E and Pierce, KA and Li, Y and Garofalo, A and Van Allen, EM and Clish, CB and Oliva, E and Mootha, VK}, title = {Early loss of mitochondrial complex I and rewiring of glutathione metabolism in renal oncocytoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6283-E6290}, pmid = {29915083}, issn = {1091-6490}, support = {P50 CA101942/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Adenoma, Oxyphilic/genetics/metabolism/pathology ; Cell Survival/genetics ; Chromosomes, Human, Pair 1/genetics/metabolism ; Cyclin D1/genetics/metabolism ; DNA, Mitochondrial/genetics/metabolism ; DNA, Neoplasm/genetics/metabolism ; Electron Transport Complex I/*deficiency ; Female ; Gene Expression Profiling ; *Glutathione/genetics/metabolism ; Humans ; *Kidney Neoplasms/genetics/metabolism/pathology ; Male ; *Mitochondria/genetics/metabolism/pathology ; Neoplasm Proteins/*deficiency ; }, abstract = {Renal oncocytomas are benign tumors characterized by a marked accumulation of mitochondria. We report a combined exome, transcriptome, and metabolome analysis of these tumors. Joint analysis of the nuclear and mitochondrial (mtDNA) genomes reveals loss-of-function mtDNA mutations occurring at high variant allele fractions, consistent with positive selection, in genes encoding complex I as the most frequent genetic events. A subset of these tumors also exhibits chromosome 1 loss and/or cyclin D1 overexpression, suggesting they follow complex I loss. Transcriptome data revealed that many pathways previously reported to be altered in renal oncocytoma were simply differentially expressed in the tumor's cell of origin, the distal nephron, compared with other nephron segments. Using a heuristic approach to account for cell-of-origin bias we uncovered strong expression alterations in the gamma-glutamyl cycle, including glutathione synthesis (increased GCLC) and glutathione degradation. Moreover, the most striking changes in metabolite profiling were elevations in oxidized and reduced glutathione as well as γ-glutamyl-cysteine and cysteinyl-glycine, dipeptide intermediates in glutathione biosynthesis, and recycling, respectively. Biosynthesis of glutathione appears adaptive as blockade of GCLC impairs viability in cells cultured with a complex I inhibitor. Our data suggest that loss-of-function mutations in complex I are a candidate driver event in renal oncocytoma that is followed by frequent loss of chromosome 1, cyclin D1 overexpression, and adaptive up-regulation of glutathione biosynthesis.}, } @article {pmid29915082, year = {2018}, author = {Weng, MW and Lee, HW and Park, SH and Hu, Y and Wang, HT and Chen, LC and Rom, WN and Huang, WC and Lepor, H and Wu, XR and Yang, CS and Tang, MS}, title = {Aldehydes are the predominant forces inducing DNA damage and inhibiting DNA repair in tobacco smoke carcinogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6152-E6161}, pmid = {29915082}, issn = {1091-6490}, support = {P01 CA165980/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P30 ES000260/ES/NIEHS NIH HHS/United States ; R01 CA190678/CA/NCI NIH HHS/United States ; }, mesh = {Aldehydes/*toxicity ; Animals ; Benzo(a)pyrene/*toxicity ; Carcinogens/*toxicity ; Cell Line ; *Cell Transformation, Neoplastic/chemically induced/genetics/metabolism/pathology ; *DNA Damage ; DNA Repair/*drug effects ; Humans ; *Lung Neoplasms/chemically induced/genetics/metabolism/pathology ; Mice ; Nitrosamines/*toxicity ; Tobacco Smoke Pollution/*adverse effects ; *Tobacco Smoking/adverse effects/pathology ; }, abstract = {Tobacco smoke (TS) contains numerous cancer-causing agents, with polycyclic aromatic hydrocarbons (PAHs) and nitrosamines being most frequently cited as the major TS human cancer agents. Many lines of evidence seriously question this conclusion. To resolve this issue, we determined DNA adducts induced by the three major TS carcinogens: benzo(a)pyrene (BP), 4-(methylnitrosamine)-1-(3-pyridyl)-1-butanoe (NNK), and aldehydes in humans and mice. In mice, TS induces abundant aldehyde-induced γ-hydroxy-propano-deoxyguanosine (γ-OH-PdG) and α-methyl-γ-OH-PdG adducts in the lung and bladder, but not in the heart and liver. TS does not induce the BP- and NNK-DNA adducts in lung, heart, liver, and bladder. TS also reduces DNA repair activity and the abundance of repair proteins, XPC and OGG1/2, in lung tissues. These TS effects were greatly reduced by diet with polyphenols. We found that γ-OH-PdG and α-methyl-γ-OH-PdG are the major adducts formed in tobacco smokers' buccal cells as well as the normal lung tissues of tobacco-smoking lung cancer patients, but not in lung tissues of nonsmokers. However, the levels of BP- and NNK-DNA adducts are the same in lung tissues of smokers and nonsmokers. We found that while BP and NNK can induce BPDE-dG and O6-methyl-dG adducts in human lung and bladder epithelial cells, these inductions can be inhibited by acrolein. Acrolein also can reduce DNA repair activity and repair proteins. We propose a TS carcinogenesis paradigm. Aldehydes are major TS carcinogens exerting dominant effect: Aldehydes induce mutagenic PdG adducts, impair DNA repair functions, and inhibit many procarcinogens in TS from becoming DNA-damaging agents.}, } @article {pmid29915081, year = {2018}, author = {Melnikov, SV and Rivera, KD and Ostapenko, D and Makarenko, A and Sanscrainte, ND and Becnel, JJ and Solomon, MJ and Texier, C and Pappin, DJ and Söll, D}, title = {Error-prone protein synthesis in parasites with the smallest eukaryotic genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6245-E6253}, pmid = {29915081}, issn = {1091-6490}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; R35 GM122560/GM/NIGMS NIH HHS/United States ; }, mesh = {*Amino Acyl-tRNA Synthetases/genetics/metabolism ; *Fungal Proteins/biosynthesis/genetics ; *Genome, Fungal ; *Microsporida/genetics/metabolism ; Protein Biosynthesis/*physiology ; RNA, Fungal/genetics/metabolism ; RNA, Transfer/genetics/metabolism ; }, abstract = {Microsporidia are parasitic fungi-like organisms that invade the interior of living cells and cause chronic disorders in a broad range of animals, including humans. These pathogens have the tiniest known genomes among eukaryotic species, for which they serve as a model for exploring the phenomenon of genome reduction in obligate intracellular parasites. Here we report a case study to show an apparent effect of overall genome reduction on the primary structure and activity of aminoacyl-tRNA synthetases, indispensable cellular proteins required for protein synthesis. We find that most microsporidian synthetases lack regulatory and eukaryote-specific appended domains and have a high degree of sequence variability in tRNA-binding and catalytic domains. In one synthetase, LeuRS, an apparent sequence degeneration annihilates the editing domain, a catalytic center responsible for the accurate selection of leucine for protein synthesis. Unlike accurate LeuRS synthetases from other eukaryotic species, microsporidian LeuRS is error-prone: apart from leucine, it occasionally uses its near-cognate substrates, such as norvaline, isoleucine, valine, and methionine. Mass spectrometry analysis of the microsporidium Vavraia culicis proteome reveals that nearly 6% of leucine residues are erroneously replaced by other amino acids. This remarkably high frequency of mistranslation is not limited to leucine codons and appears to be a general property of protein synthesis in microsporidian parasites. Taken together, our findings reveal that the microsporidian protein synthesis machinery is editing-deficient, and that the proteome of microsporidian parasites is more diverse than would be anticipated based on their genome sequences.}, } @article {pmid29915080, year = {2018}, author = {Kurihara, Y and Makita, Y and Kawashima, M and Fujita, T and Iwasaki, S and Matsui, M}, title = {Transcripts from downstream alternative transcription start sites evade uORF-mediated inhibition of gene expression in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7831-7836}, pmid = {29915080}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Basic-Leucine Zipper Transcription Factors/genetics/*metabolism ; Carrier Proteins/genetics/*metabolism ; Gene Expression Regulation, Plant/*physiology ; Nuclear Proteins/genetics/*metabolism ; Open Reading Frames/*physiology ; Transcription Initiation Site/*physiology ; }, abstract = {Plants adapt to alterations in light conditions by controlling their gene expression profiles. Expression of light-inducible genes is transcriptionally induced by transcription factors such as HY5. However, few detailed analyses have been carried out on the control of transcription start sites (TSSs). Of the various wavelengths of light, it is blue light (BL) that regulates physiological responses such as hypocotyl elongation and flowering time. To understand how gene expression is controlled not only by transcript abundance but also by TSS selection, we examined genome-wide TSS profiles in Arabidopsis seedlings after exposure to BL irradiation following initial growth in the dark. Thousands of genes use multiple TSSs, and some transcripts have upstream ORFs (uORFs) that take precedence over the main ORF (mORF) encoding proteins. The uORFs often function as translation inhibitors of the mORF or as triggers of nonsense-mediated mRNA decay (NMD). Transcription from TSSs located downstream of the uORFs in 220 genes is enhanced by BL exposure. This type of regulation is found in HY5 and HYH, major regulators of light-dependent gene expression. Translation efficiencies of the genes showing enhanced usage of these TSSs increased upon BL exposure. We also show that transcripts from TSSs upstream of uORFs in 45 of the 220 genes, including HY5, accumulated in a mutant of NMD. These results suggest that BL controls gene expression not only by enhancing transcriptions but also by choosing the TSS, and transcripts from downstream TSSs evade uORF-mediated inhibition to ensure high expression of light-regulated genes.}, } @article {pmid29915079, year = {2018}, author = {Goldman, N and Glei, DA and Weinstein, M}, title = {Declining mental health among disadvantaged Americans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7290-7295}, pmid = {29915079}, issn = {1091-6490}, support = {UL1 TR000427/TR/NCATS NIH HHS/United States ; M01 RR000865/RR/NCRR NIH HHS/United States ; P2C HD047879/HD/NICHD NIH HHS/United States ; M01 RR023942/RR/NCRR NIH HHS/United States ; P01 AG020166/AG/NIA NIH HHS/United States ; U19 AG051426/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; Aged ; *Emotions ; Female ; Humans ; Male ; *Mental Health ; Middle Aged ; Socioeconomic Factors ; Substance-Related Disorders/*epidemiology/*psychology ; United States/epidemiology ; }, abstract = {Although there is little dispute about the impact of the US opioid epidemic on recent mortality, there is less consensus about whether trends reflect increasing despair among American adults. The issue is complicated by the absence of established scales or definitions of despair as well as a paucity of studies examining changes in psychological health, especially well-being, since the 1990s. We contribute evidence using two cross-sectional waves of the Midlife in the United States (MIDUS) study to assess changes in measures of psychological distress and well-being. These measures capture negative emotions such as sadness, hopelessness, and worthlessness, and positive emotions such as happiness, fulfillment, and life satisfaction. Most of the measures reveal increasing distress and decreasing well-being across the age span for those of low relative socioeconomic position, in contrast to little decline or modest improvement for persons of high relative position.}, } @article {pmid29915078, year = {2018}, author = {Ding, Q and Gaska, JM and Douam, F and Wei, L and Kim, D and Balev, M and Heller, B and Ploss, A}, title = {Species-specific disruption of STING-dependent antiviral cellular defenses by the Zika virus NS2B3 protease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6310-E6318}, pmid = {29915078}, issn = {1091-6490}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; R01 AI107301/AI/NIAID NIH HHS/United States ; R21 AI117213/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cercopithecus aethiops ; HEK293 Cells ; Humans ; *Immunity, Innate ; Membrane Proteins/genetics/*immunology ; Mice ; Peptide Hydrolases/genetics/*immunology ; *Proteolysis ; Signal Transduction/genetics/immunology ; Species Specificity ; Vero Cells ; Viral Nonstructural Proteins/genetics/*immunology ; Zika Virus/genetics/*immunology ; }, abstract = {The limited host tropism of numerous viruses causing disease in humans remains incompletely understood. One example is Zika virus (ZIKV), an RNA virus that has reemerged in recent years. Here, we demonstrate that ZIKV efficiently infects fibroblasts from humans, great apes, New and Old World monkeys, but not rodents. ZIKV infection in human-but not murine-cells impairs responses to agonists of the cGMP-AMP synthase/stimulator of IFN genes (cGAS/STING) signaling pathway, suggesting that viral mechanisms to evade antiviral defenses are less effective in rodent cells. Indeed, human, but not mouse, STING is subject to cleavage by proteases encoded by ZIKV, dengue virus, West Nile virus, and Japanese encephalitis virus, but not that of yellow fever virus. The protease cleavage site, located between positions 78/79 of human STING, is only partially conserved in nonhuman primates and rodents, rendering these orthologs resistant to degradation. Genetic disruption of STING increases the susceptibility of mouse-but not human-cells to ZIKV. Accordingly, expression of only mouse, not human, STING in murine STING knockout cells rescues the ZIKV suppression phenotype. STING-deficient mice, however, did not exhibit increased susceptibility, suggesting that other redundant antiviral pathways control ZIKV infection in vivo. Collectively, our data demonstrate that numerous RNA viruses evade cGAS/STING-dependent signaling and affirm the importance of this pathway in shaping the host range of ZIKV. Furthermore, our results explain-at least in part-the decreased permissivity of rodent cells to ZIKV, which could aid in the development of mice model with inheritable susceptibility to ZIKV and other flaviviruses.}, } @article {pmid29915077, year = {2018}, author = {Treml, B and Gillman, A and Buskohl, P and Vaia, R}, title = {Origami mechanologic.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6916-6921}, pmid = {29915077}, issn = {1091-6490}, abstract = {Robots autonomously interact with their environment through a continual sense-decide-respond control loop. Most commonly, the decide step occurs in a central processing unit; however, the stiffness mismatch between rigid electronics and the compliant bodies of soft robots can impede integration of these systems. We develop a framework for programmable mechanical computation embedded into the structure of soft robots that can augment conventional digital electronic control schemes. Using an origami waterbomb as an experimental platform, we demonstrate a 1-bit mechanical storage device that writes, erases, and rewrites itself in response to a time-varying environmental signal. Further, we show that mechanical coupling between connected origami units can be used to program the behavior of a mechanical bit, produce logic gates such as AND, OR, and three input majority gates, and transmit signals between mechanologic gates. Embedded mechanologic provides a route to add autonomy and intelligence in soft robots and machines.}, } @article {pmid29915076, year = {2018}, author = {Lin, M and Kang, S and Shaheen, R and Li, C and Hsu, SC and Thiemens, MH}, title = {Atmospheric sulfur isotopic anomalies recorded at Mt. Everest across the Anthropocene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6964-6969}, pmid = {29915076}, issn = {1091-6490}, mesh = {Air/*analysis ; Sulfur Isotopes/*chemistry ; }, abstract = {Increased anthropogenic-induced aerosol concentrations over the Himalayas and Tibetan Plateau have affected regional climate, accelerated snow/glacier melting, and influenced water supply and quality in Asia. Although sulfate is a predominant chemical component in aerosols and the hydrosphere, the contributions from different sources remain contentious. Here, we report multiple sulfur isotope composition of sedimentary sulfates from a remote freshwater alpine lake near Mount Everest to reconstruct a two-century record of the atmospheric sulfur cycle. The sulfur isotopic anomaly is utilized as a probe for sulfur source apportionment and chemical transformation history. The nineteenth-century record displays a distinct sulfur isotopic signature compared with the twentieth-century record when sulfate concentrations increased. Along with other elemental measurements, the isotopic proxy suggests that the increased trend of sulfate is mainly attributed to enhancements of dust-associated sulfate aerosols and climate-induced weathering/erosion, which overprinted sulfur isotopic anomalies originating from other sources (e.g., sulfates produced in the stratosphere by photolytic oxidation processes and/or emitted from combustion) as observed in most modern tropospheric aerosols. The changes in sulfur cycling reported in this study have implications for better quantification of radiative forcing and snow/glacier melting at this climatically sensitive region and potentially other temperate glacial hydrological systems. Additionally, the unique Δ33S-δ34S pattern in the nineteenth century, a period with extensive global biomass burning, is similar to the Paleoarchean (3.6-3.2 Ga) barite record, potentially providing a deeper insight into sulfur photochemical/thermal reactions and possible volcanic influences on the Earth's earliest sulfur cycle.}, } @article {pmid29915075, year = {2018}, author = {Zheng, T and Xie, J and Yang, Z and Tao, P and Shi, B and Douthit, L and Wu, P and Lerner, RA}, title = {Antibody selection using clonal cocultivation of Escherichia coli and eukaryotic cells in miniecosystems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6145-E6151}, pmid = {29915075}, issn = {1091-6490}, mesh = {Animals ; *Bacteriophage M13/genetics/immunology ; CHO Cells ; Coculture Techniques ; Cricetulus ; *Escherichia coli/genetics/immunology ; Humans ; Membrane Glycoproteins/*antagonists & inhibitors/immunology ; Receptor, trkB/*antagonists & inhibitors/immunology ; *Single-Chain Antibodies/genetics/immunology ; }, abstract = {We describe a method for the rapid selection of functional antibodies. The method depends on the cocultivation of Escherichia coli that produce phage with target eukaryotic cells in very small volumes. The antibodies on phage induce selectable phenotypes in the target cells, and the nature of the antibody is determined by gene sequencing of the phage genome. To select functional antibodies from the diverse antibody repertoire, we devised a selection platform that contains millions of picoliter-sized droplet ecosystems. In each miniecosystem, the bacteria produce phage displaying unique members of the antibody repertoire. These phage interact only with eukaryotic cells in the same miniecosystem, making phage available directly for activity-based antibody selection in biological systems.}, } @article {pmid29915074, year = {2018}, author = {Piscopo, DM and Weible, AP and Rothbart, MK and Posner, MI and Niell, CM}, title = {Changes in white matter in mice resulting from low-frequency brain stimulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6339-E6346}, pmid = {29915074}, issn = {1091-6490}, mesh = {Animals ; Anxiety/pathology/*physiopathology ; Corpus Callosum/pathology/*physiopathology ; *Deep Brain Stimulation ; Mice ; *Optogenetics ; White Matter/pathology/*physiopathology ; }, abstract = {Recent reports have begun to elucidate mechanisms by which learning and experience produce white matter changes in the brain. We previously reported changes in white matter surrounding the anterior cingulate cortex in humans after 2-4 weeks of meditation training. We further found that low-frequency optogenetic stimulation of the anterior cingulate in mice increased time spent in the light in a light/dark box paradigm, suggesting decreased anxiety similar to what is observed following meditation training. Here, we investigated the impact of this stimulation at the cellular level. We found that laser stimulation in the range of 1-8 Hz results in changes to subcortical white matter projection fibers in the corpus callosum. Specifically, stimulation resulted in increased oligodendrocyte proliferation, accompanied by a decrease in the g-ratio within the corpus callosum underlying the anterior cingulate cortex. These results suggest that low-frequency stimulation can result in activity-dependent remodeling of myelin, giving rise to enhanced connectivity and altered behavior.}, } @article {pmid29915073, year = {2018}, author = {Rozsa, V and Pan, D and Giberti, F and Galli, G}, title = {Ab initio spectroscopy and ionic conductivity of water under Earth mantle conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6952-6957}, pmid = {29915073}, issn = {1091-6490}, abstract = {The phase diagram of water at extreme conditions plays a critical role in Earth and planetary science, yet remains poorly understood. Here we report a first-principles investigation of the liquid at high temperature, between 11 GPa and 20 GPa-a region where numerous controversial results have been reported over the past three decades. Our results are consistent with the recent estimates of the water melting line below 1,000 K and show that on the 1,000-K isotherm the liquid is rapidly dissociating and recombining through a bimolecular mechanism. We found that short-lived ionic species act as charge carriers, giving rise to an ionic conductivity that at 11 GPa and 20 GPa is six and seven orders of magnitude larger, respectively, than at ambient conditions. Conductivity calculations were performed entirely from first principles, with no a priori assumptions on the nature of charge carriers. Despite frequent dissociative events, we observed that hydrogen bonding persists at high pressure, up to at least 20 GPa. Our computed Raman spectra, which are in excellent agreement with experiment, show no distinctive signatures of the hydronium and hydroxide ions present in our simulations. Instead, we found that infrared spectra are sensitive probes of molecular dissociation, exhibiting a broad band below the OH stretching mode ascribable to vibrations of complex ions.}, } @article {pmid29915072, year = {2018}, author = {Lee, JW and Park, YH and Seok, YJ}, title = {Rsd balances (p)ppGpp level by stimulating the hydrolase activity of SpoT during carbon source downshift in Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6845-E6854}, pmid = {29915072}, issn = {1091-6490}, mesh = {Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Guanosine Pentaphosphate/genetics/*metabolism ; Pyrophosphatases/genetics/*metabolism ; Repressor Proteins/genetics/*metabolism ; }, abstract = {Bacteria respond to nutritional stresses by changing the cellular concentration of the alarmone (p)ppGpp. This control mechanism, called the stringent response, depends on two enzymes, the (p)ppGpp synthetase RelA and the bifunctional (p)ppGpp synthetase/hydrolase SpoT in Escherichia coli and related bacteria. Because SpoT is the only enzyme responsible for (p)ppGpp hydrolysis in these bacteria, SpoT activity needs to be tightly regulated to prevent the uncontrolled accumulation of (p)ppGpp, which is lethal. To date, however, no such regulation of SpoT (p)ppGpp hydrolase activity has been documented in E. coli In this study, we show that Rsd directly interacts with SpoT and stimulates its (p)ppGpp hydrolase activity. Dephosphorylated HPr, but not phosphorylated HPr, of the phosphoenolpyruvate-dependent sugar phosphotransferase system could antagonize the stimulatory effect of Rsd on SpoT (p)ppGpp hydrolase activity. Thus, we suggest that Rsd is a carbon source-dependent regulator of the stringent response in E. coli.}, } @article {pmid29915071, year = {2018}, author = {Pathak, PK and Peng, S and Meng, X and Han, Y and Zhang, B and Zhang, F and Xiang, Y and Deng, J}, title = {Structure of a lipid-bound viral membrane assembly protein reveals a modality for enclosing the lipid bilayer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7028-7032}, pmid = {29915071}, issn = {1091-6490}, support = {R01 AI079217/AI/NIAID NIH HHS/United States ; R21 AI133589/AI/NIAID NIH HHS/United States ; }, mesh = {Crystallography, X-Ray ; Lipid Bilayers/*chemistry ; Membrane Proteins/*chemistry/genetics ; Vaccinia virus/*chemistry/genetics ; Viral Proteins/*chemistry/genetics ; }, abstract = {Cellular membranes are maintained as closed compartments, broken up only transiently during membrane reorganization or lipid transportation. However, open-ended membranes, likely derived from scissions of the endoplasmic reticulum, persist in vaccinia virus-infected cells during the assembly of the viral envelope. A group of viral membrane assembly proteins (VMAPs) were identified as essential for this process. To understand the mechanism of VMAPs, we determined the 2.2-Å crystal structure of the largest member, named A6, which is a soluble protein with two distinct domains. The structure of A6 displays a novel protein fold composed mainly of alpha helices. The larger C-terminal domain forms a unique cage that encloses multiple glycerophospholipids with a lipid bilayer-like configuration. The smaller N-terminal domain does not bind lipid but negatively affects lipid binding by A6. Mutations of key hydrophobic residues lining the lipid-binding cage disrupt lipid binding and abolish viral replication. Our results reveal a protein modality for enclosing the lipid bilayer and provide molecular insight into a viral machinery involved in generating and/or stabilizing open-ended membranes.}, } @article {pmid29915070, year = {2018}, author = {Harris, KA and Zhou, Z and Peters, ML and Wilkins, SG and Breaker, RR}, title = {A second RNA-binding protein is essential for ethanol tolerance provided by the bacterial OLE ribonucleoprotein complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6319-E6328}, pmid = {29915070}, issn = {1091-6490}, support = {F32 GM116426/GM/NIGMS NIH HHS/United States ; P01 GM022778/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Bacillus/genetics/metabolism ; *Bacterial Proteins/genetics/metabolism ; *Drug Resistance, Bacterial/drug effects/genetics ; Ethanol/*pharmacology ; *RNA-Binding Proteins/genetics/metabolism ; }, abstract = {OLE (ornate, large, extremophilic) RNAs comprise a class of structured noncoding RNAs (ncRNAs) found in many extremophilic bacteria species. OLE RNAs constitute one of the longest and most widespread bacterial ncRNA classes whose major biochemical function remains unknown. In the Gram-positive alkaliphile Bacillus halodurans, OLE RNA is abundant, and localizes to the cell membrane by association with the transmembrane OLE-associated protein called OapA (formerly OAP). These characteristics, along with the well-conserved sequence and structural features of OLE RNAs, suggest that the OLE ribonucleoprotein (RNP) complex performs important biological functions. B. halodurans strains lacking OLE RNA (∆ole) or OapA (∆oapA) are less tolerant of cold (20 °C) and short-chain alcohols (e.g., ethanol). Here, we describe the effects of a mutant OapA (called PM1) that more strongly inhibits growth under cold or ethanol stress compared with strains lacking the oapA gene, even when wild-type OapA is present. This dominant-negative effect of PM1 is reversed by mutations that render OLE RNA nonfunctional. This finding demonstrates that the deleterious PM1 phenotype requires an intact RNP complex, and suggests that the complex has one or more additional undiscovered components. A genetic screen uncovered PM1 phenotype suppressor mutations in the ybzG gene, which codes for a putative RNA-binding protein of unknown biological function. We observe that YbzG protein (also called OapB) selectively binds OLE RNA in vitro, whereas a mutant version of the protein is not observed to bind OLE RNA. Thus, YbzG/OapB is an important component of the functional OLE RNP complex in B. halodurans.}, } @article {pmid29915069, year = {2018}, author = {Fluet-Chouinard, E and Funge-Smith, S and McIntyre, PB}, title = {Global hidden harvest of freshwater fish revealed by household surveys.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {7623-7628}, pmid = {29915069}, issn = {1091-6490}, mesh = {Animals ; Dietary Proteins/*supply & distribution ; *Family Characteristics ; *Fisheries ; *Fishes ; *Food Supply ; *Fresh Water ; }, abstract = {Consumption of wild-caught freshwater fish is concentrated in low-income countries, where it makes a critical contribution to food security and livelihoods. Underestimation of inland harvests in official statistics has long been suspected due to unmonitored subsistence fisheries. To overcome the lack of data from extensive small-scale harvests, we used household consumption surveys to estimate freshwater fish catches in 42 low- and middle-income countries between 1997 and 2014. After accounting for trade and aquaculture, these countries collectively consumed 3.6 MT (CI, 1.5-5.8) more wild-caught freshwater fish than officially reported, reflecting a net underreporting of 64.8% (CI, 27.1-103.9%). Individual countries were more likely to underestimate (n = 31) than overestimate (n = 11) catches, despite conservative assumptions in our calculations. Extrapolating our findings suggests that the global inland catch reported as 10.3 MT in 2008 was more likely 16.6 MT (CI, 2.3-30.9), which accords with recent independent predictions for rivers and lakes. In human terms, these hidden harvests are equivalent to the total animal protein consumption of 36.9 (CI, 30.8-43.4) million people, including many who rely upon wild fish to achieve even minimal protein intake. The widespread underreporting uncovered by household consumption surveys indicates that inland fisheries contribute far more to global food security than has been recognized previously. Our findings also amplify concerns about the sustainability of intensive fishery exploitation as degradation of rivers, lakes, and wetlands continues apace.}, } @article {pmid29915068, year = {2018}, author = {Shalit-Kaneh, A and Kumimoto, RW and Filkov, V and Harmer, SL}, title = {Multiple feedback loops of the Arabidopsis circadian clock provide rhythmic robustness across environmental conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7147-7152}, pmid = {29915068}, issn = {1091-6490}, support = {R01 GM069418/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Circadian Clocks/*physiology ; DNA-Binding Proteins/genetics/*metabolism ; Gene Regulatory Networks/*physiology ; Signal Transduction/*physiology ; Transcription Factors/genetics/*metabolism ; }, abstract = {Although circadian oscillators in diverse eukaryotes all depend on interlinked transcriptional feedback loops, specific components are not conserved across higher taxa. Moreover, the circadian network in the model plant Arabidopsis thaliana is notably more complex than those found in animals and fungi. Here, we combine mathematical modeling and experimental approaches to investigate the functions of two classes of Myb-like transcription factors that antagonistically regulate common target genes. Both CCA1/LHY- and RVE8-clade factors bind directly to the same cis-element, but the former proteins act primarily as repressors, while the latter act primarily as activators of gene expression. We find that simulation of either type of loss-of-function mutant recapitulates clock phenotypes previously reported in mutant plants, while simulated simultaneous loss of both type of factors largely rescues circadian phase at the expense of rhythmic amplitude. In accord with this prediction, we find that plants mutant for both activator- and repressor-type Mybs have near-normal circadian phase and period but reduced rhythmic amplitude. Although these mutants exhibit robust rhythms when grown at mild temperatures, they are largely arrhythmic at physiologically relevant but nonoptimal temperatures. LHY- and RVE8-type Mybs are found in separate clades across the land plant lineage and even in some unicellular green algae, suggesting that they both may have functioned in even the earliest arising plant circadian oscillators. Our data suggest that the complexity of the plant circadian network may have arisen to provide rhythmic robustness across the range of environmental extremes to which plants, as sessile organisms, are regularly subjected.}, } @article {pmid29915067, year = {2018}, author = {Wu, Y and Xi, X and Tang, X and Luo, D and Gu, B and Lam, SK and Vitousek, PM and Chen, D}, title = {Policy distortions, farm size, and the overuse of agricultural chemicals in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7010-7015}, pmid = {29915067}, issn = {1091-6490}, support = {BB/N013484/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Agrochemicals/*economics ; China ; Crop Production/*economics/*legislation & jurisprudence ; Humans ; *Models, Economic ; }, abstract = {Understanding the reasons for overuse of agricultural chemicals is critical to the sustainable development of Chinese agriculture. Using a nationally representative rural household survey from China, we found that farm size is a strong factor that affects the use intensity of agricultural chemicals across farms in China. Statistically, a 1% increase in farm size is associated with a 0.3% and 0.5% decrease in fertilizer and pesticide use per hectare (P < 0.001), respectively, and an almost 1% increase in agricultural labor productivity, while it only leads to a statistically insignificant 0.02% decrease in crop yields. The same pattern was also found using other independently collected data sources from China and an international panel analysis of 74 countries from the 1960s to the 2000s. While economic growth has been associated with increasing farm size in many other countries, in China this relationship has been distorted by land and migration policies, leading to the persistence of small farm size in China. Removing these distortions would decrease agricultural chemical use by 30-50% and the environmental impact of those chemicals by 50% while doubling the total income of all farmers including those who move to urban areas. Removing policy distortions is also likely to complement other remedies to the overuse problem, such as easing farmer's access to modern technologies and knowledge, and improving environmental regulation and enforcement.}, } @article {pmid29915066, year = {2018}, author = {Cinner, JE and Maire, E and Huchery, C and MacNeil, MA and Graham, NAJ and Mora, C and McClanahan, TR and Barnes, ML and Kittinger, JN and Hicks, CC and D'Agata, S and Hoey, AS and Gurney, GG and Feary, DA and Williams, ID and Kulbicki, M and Vigliola, L and Wantiez, L and Edgar, GJ and Stuart-Smith, RD and Sandin, SA and Green, A and Hardt, MJ and Beger, M and Friedlander, AM and Wilson, SK and Brokovich, E and Brooks, AJ and Cruz-Motta, JJ and Booth, DJ and Chabanet, P and Gough, C and Tupper, M and Ferse, SCA and Sumaila, UR and Pardede, S and Mouillot, D}, title = {Gravity of human impacts mediates coral reef conservation gains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6116-E6125}, pmid = {29915066}, issn = {1091-6490}, mesh = {Animals ; *Biomass ; *Conservation of Natural Resources ; *Coral Reefs ; Fishes/*physiology ; *Food Chain ; Humans ; }, abstract = {Coral reefs provide ecosystem goods and services for millions of people in the tropics, but reef conditions are declining worldwide. Effective solutions to the crisis facing coral reefs depend in part on understanding the context under which different types of conservation benefits can be maximized. Our global analysis of nearly 1,800 tropical reefs reveals how the intensity of human impacts in the surrounding seascape, measured as a function of human population size and accessibility to reefs ("gravity"), diminishes the effectiveness of marine reserves at sustaining reef fish biomass and the presence of top predators, even where compliance with reserve rules is high. Critically, fish biomass in high-compliance marine reserves located where human impacts were intensive tended to be less than a quarter that of reserves where human impacts were low. Similarly, the probability of encountering top predators on reefs with high human impacts was close to zero, even in high-compliance marine reserves. However, we find that the relative difference between openly fished sites and reserves (what we refer to as conservation gains) are highest for fish biomass (excluding predators) where human impacts are moderate and for top predators where human impacts are low. Our results illustrate critical ecological trade-offs in meeting key conservation objectives: reserves placed where there are moderate-to-high human impacts can provide substantial conservation gains for fish biomass, yet they are unlikely to support key ecosystem functions like higher-order predation, which is more prevalent in reserve locations with low human impacts.}, } @article {pmid29915065, year = {2018}, author = {Mok, WWK and Brynildsen, MP}, title = {Timing of DNA damage responses impacts persistence to fluoroquinolones.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6301-E6309}, pmid = {29915065}, issn = {1091-6490}, mesh = {*DNA Damage ; DNA-Binding Proteins/genetics/*metabolism ; Endoribonucleases/genetics/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Microbial Viability/*drug effects ; Ofloxacin/*pharmacology ; }, abstract = {Bacterial persisters are subpopulations of phenotypic variants in isogenic cultures that can survive lethal doses of antibiotics. Their tolerances are often attributed to reduced activities of antibiotic targets, which limit corruption and damage in persisters compared with bacteria that die from treatment. However, that model does not hold for nongrowing populations treated with ofloxacin, a fluoroquinolone, where antibiotic-induced damage is comparable between cells that live and those that die. To understand how those persisters achieve this feat, we employed a genetic system that uses orthogonal control of MazF and MazE, a toxin and its cognate antitoxin, to generate model persisters that are uniformly tolerant to ofloxacin. Despite this complete tolerance, MazF model persisters required the same DNA repair machinery (RecA, RecB, and SOS induction) to survive ofloxacin treatment as their nongrowing, WT counterparts and exhibited similar indicators of DNA damage from treatment. Further investigation revealed that, following treatment, the timing of DNA repair was critical to MazF persister survival because, when repair was delayed until after growth and DNA synthesis resumed, survival was compromised. In addition, we found that, with nongrowing, WT planktonic and biofilm populations, stalling the resumption of growth and DNA synthesis after the conclusion of fluoroquinolone treatment with a prevalent type of stress at infection sites (nutrient limitation) led to near complete survival. These findings illustrate that the timing of events, such as DNA repair, following fluoroquinolone treatment is important to persister survival and provide further evidence that knowledge of the postantibiotic recovery period is critical to understanding persistence phenotypes.}, } @article {pmid29915064, year = {2018}, author = {Sarem, M and Heizmann, M and Barbero, A and Martin, I and Shastri, VP}, title = {Hyperstimulation of CaSR in human MSCs by biomimetic apatite inhibits endochondral ossification via temporal down-regulation of PTH1R.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6135-E6144}, pmid = {29915064}, issn = {1091-6490}, mesh = {Adult ; Apatites/*pharmacology ; Biomimetic Materials/*pharmacology ; Chondrogenesis/drug effects ; Down-Regulation/*drug effects ; Female ; Humans ; Male ; Mesenchymal Stem Cells/cytology/*metabolism ; Osteogenesis/*drug effects ; Parathyroid Hormone/pharmacology ; Periosteum/cytology/*metabolism ; Receptor, Parathyroid Hormone, Type 1/*biosynthesis ; Receptors, Calcium-Sensing/*metabolism ; Transforming Growth Factor beta1/metabolism ; }, abstract = {In adult bone injuries, periosteum-derived mesenchymal stem/stromal cells (MSCs) form bone via endochondral ossification (EO), whereas those from bone marrow (BM)/endosteum form bone primarily through intramembranous ossification (IMO). We hypothesized that this phenomenon is influenced by the proximity of MSCs residing in the BM to the trabecular bone microenvironment. Herein, we investigated the impact of the bone mineral phase on human BM-derived MSCs' choice of ossification pathway, using a biomimetic bone-like hydroxyapatite (BBHAp) interface. BBHAp induced hyperstimulation of extracellular calcium-sensing receptor (CaSR) and temporal down-regulation of parathyroid hormone 1 receptor (PTH1R), leading to inhibition of chondrogenic differentiation of MSCs even in the presence of chondroinductive factors, such as transforming growth factor-β1 (TGF-β1). Interestingly rescuing PTH1R expression using human PTH fragment (1-34) partially restored chondrogenesis in the BBHAp environment. In vivo studies in an ectopic site revealed that the BBHAp interface inhibits EO and strictly promotes IMO. Furthermore, CaSR knockdown (CaSR KD) disrupted the bone-forming potential of MSCs irrespective of the absence or presence of the BBHAp interface. Our findings confirm the expression of CaSR in human BM-derived MSCs and unravel a prominent role for the interplay between CaSR and PTH1R in regulating MSC fate and the choice of pathway for bone formation.}, } @article {pmid29915063, year = {2018}, author = {Becerra-Valdivia, L and Waters, MR and Stafford, TW and Anzick, SL and Comeskey, D and Devièse, T and Higham, T}, title = {Reassessing the chronology of the archaeological site of Anzick.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7000-7003}, pmid = {29915063}, issn = {1091-6490}, mesh = {*Anthropology, Cultural ; Chronology as Topic ; *Databases, Factual ; Female ; History, Ancient ; Humans ; *Indians, North American ; Male ; Montana ; }, abstract = {Found in 1968, the archaeological site of Anzick, Montana, contains the only known Clovis burial. Here, the partial remains of a male infant, Anzick-1, were found in association with a Clovis assemblage of over 100 lithic and osseous artifacts-all red-stained with ochre. The incomplete, unstained cranium of an unassociated, geologically younger individual, Anzick-2, was also recovered. Previous chronometric work has shown an age difference between Anzick-1 and the Clovis assemblage (represented by dates from two antler rod samples). This discrepancy has led to much speculation, with some discounting Anzick-1 as Clovis. To resolve this issue, we present the results of a comprehensive radiocarbon dating program that utilized different pretreatment methods on osseous material from the site. Through this comparative approach, we obtained a robust chronometric dataset that suggests that Anzick-1 is temporally coeval with the dated antler rods. This implies that the individual is indeed temporally associated with the Clovis assemblage.}, } @article {pmid29915062, year = {2018}, author = {Conith, MR and Hu, Y and Conith, AJ and Maginnis, MA and Webb, JF and Albertson, RC}, title = {Genetic and developmental origins of a unique foraging adaptation in a Lake Malawi cichlid genus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7063-7068}, pmid = {29915062}, issn = {1091-6490}, mesh = {ADAM12 Protein/*genetics ; *Adaptation, Physiological ; Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Cichlids/*genetics ; Fish Proteins/*genetics ; Lakes ; Malawi ; Transforming Growth Factor beta/*genetics ; }, abstract = {Phenotypic novelties are an important but poorly understood category of morphological diversity. They can provide insights into the origins of phenotypic variation, but we know relatively little about their genetic origins. Cichlid fishes display remarkable diversity in craniofacial anatomy, including several novelties. One aspect of this variation is a conspicuous, exaggerated snout that has evolved in a single Malawi cichlid lineage and is associated with foraging specialization and increased ecological success. We examined the developmental and genetic origins for this phenotype and found that the snout is composed of two hypertrophied tissues: the intermaxillary ligament (IML), which connects the right and left sides of the upper jaw, and the overlying loose connective tissue. The IML is present in all cichlids, but in its exaggerated form it interdigitates with the more superficial connective tissue and anchors to the epithelium, forming a unique ligament-epithelial complex. We examined the Transforming growth factor β (Tgfβ) → Scleraxis (Scx) candidate pathway and confirmed a role for these factors in snout development. We demonstrate further that experimental up-regulation of Tgfβ is sufficient to produce an expansion of scx expression and concomitant changes in snout morphology. Genetic and genomic mapping show that core members of canonical Tgfβ signaling segregate with quantitative trait loci (QTL) for snout variation. These data also implicate a candidate for ligament development, adam12, which we confirm using the zebrafish model. Collectively, these data provide insights into ligament morphogenesis, as well as how an ecologically relevant novelty can arise at the molecular level.}, } @article {pmid29915061, year = {2018}, author = {Buser, DP and Schleicher, KD and Prescianotto-Baschong, C and Spiess, M}, title = {A versatile nanobody-based toolkit to analyze retrograde transport from the cell surface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6227-E6236}, pmid = {29915061}, issn = {1091-6490}, mesh = {Adaptor Protein Complex 1/*metabolism ; Animals ; Biological Transport, Active/physiology ; Camelus ; Cell Membrane/*metabolism ; DNA-(Apurinic or Apyrimidinic Site) Lyase/*metabolism ; Endosomes/*metabolism/ultrastructure ; Green Fluorescent Proteins/metabolism ; HeLa Cells ; Humans ; Microscopy, Electron ; Microscopy, Fluorescence ; Receptor, IGF Type 2/*metabolism ; Single-Domain Antibodies/*metabolism ; trans-Golgi Network/*metabolism/ultrastructure ; }, abstract = {Retrograde transport of membranes and proteins from the cell surface to the Golgi and beyond is essential to maintain homeostasis, compartment identity, and physiological functions. To study retrograde traffic biochemically, by live-cell imaging or by electron microscopy, we engineered functionalized anti-GFP nanobodies (camelid VHH antibody domains) to be bacterially expressed and purified. Tyrosine sulfation consensus sequences were fused to the nanobody for biochemical detection of trans-Golgi arrival, fluorophores for fluorescence microscopy and live imaging, and APEX2 (ascorbate peroxidase 2) for electron microscopy and compartment ablation. These functionalized nanobodies are specifically captured by GFP-modified reporter proteins at the cell surface and transported piggyback to the reporters' homing compartments. As an application of this tool, we have used it to determine the contribution of adaptor protein-1/clathrin in retrograde transport kinetics of the mannose-6-phosphate receptors from endosomes back to the trans-Golgi network. Our experiments establish functionalized nanobodies as a powerful tool to demonstrate and quantify retrograde transport pathways.}, } @article {pmid29915060, year = {2018}, author = {Chen, MB and Hajal, C and Benjamin, DC and Yu, C and Azizgolshani, H and Hynes, RO and Kamm, RD}, title = {Inflamed neutrophils sequestered at entrapped tumor cells via chemotactic confinement promote tumor cell extravasation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7022-7027}, pmid = {29915060}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Cell Line, Tumor ; Chemokine CXCL1/*immunology ; Chemotaxis/drug effects/*immunology ; Humans ; Interleukin-8/*immunology ; Lipopolysaccharides/pharmacology ; Microfluidic Analytical Techniques/methods ; Neoplasm Proteins/*immunology ; Neoplasms/*immunology/pathology ; Neutrophils/*immunology/pathology ; Zebrafish ; }, abstract = {Systemic inflammation occurring around the course of tumor progression and treatment are often correlated with adverse oncological outcomes. As such, it is suspected that neutrophils, the first line of defense against infection, may play important roles in linking inflammation and metastatic seeding. To decipher the dynamic roles of inflamed neutrophils during hematogenous dissemination, we employ a multiplexed microfluidic model of the human microvasculature enabling physiologically relevant transport of circulating cells combined with real-time, high spatial resolution observation of heterotypic cell-cell interactions. LPS-stimulated neutrophils (PMNs) and tumor cells (TCs) form heterotypic aggregates under flow, and arrest due to both mechanical trapping and neutrophil-endothelial adhesions. Surprisingly, PMNs are not static following aggregation, but exhibit a confined migration pattern near TC-PMN clusters. We discover that PMNs are chemotactically confined by self-secreted IL-8 and tumor-derived CXCL-1, which are immobilized by the endothelial glycocalyx. This results in significant neutrophil sequestration with arrested tumor cells, leading to the spatial localization of neutrophil-derived IL-8, which also contributes to increasing the extravasation potential of adjacent tumor cells through modulation of the endothelial barrier. Strikingly similar migration patterns and extravasation behaviors were also observed in an in vivo zebrafish model upon PMN-tumor cell coinjection into the embryo vasculature. These insights into the temporal dynamics of intravascular tumor-PMN interactions elucidate the mechanisms through which inflamed neutrophils can exert proextravasation effects at the distant metastatic site.}, } @article {pmid29915059, year = {2018}, author = {Fisher, AJ and Medaglia, JD and Jeronimus, BF}, title = {Lack of group-to-individual generalizability is a threat to human subjects research.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6106-E6115}, pmid = {29915059}, issn = {1091-6490}, support = {DP5 OD021352/OD/NIH HHS/United States ; }, mesh = {Anxiety Disorders/*therapy ; Bipolar Disorder/*therapy ; Female ; Humans ; Male ; *Psychotherapy, Group ; }, abstract = {Only for ergodic processes will inferences based on group-level data generalize to individual experience or behavior. Because human social and psychological processes typically have an individually variable and time-varying nature, they are unlikely to be ergodic. In this paper, six studies with a repeated-measure design were used for symmetric comparisons of interindividual and intraindividual variation. Our results delineate the potential scope and impact of nonergodic data in human subjects research. Analyses across six samples (with 87-94 participants and an equal number of assessments per participant) showed some degree of agreement in central tendency estimates (mean) between groups and individuals across constructs and data collection paradigms. However, the variance around the expected value was two to four times larger within individuals than within groups. This suggests that literatures in social and medical sciences may overestimate the accuracy of aggregated statistical estimates. This observation could have serious consequences for how we understand the consistency between group and individual correlations, and the generalizability of conclusions between domains. Researchers should explicitly test for equivalence of processes at the individual and group level across the social and medical sciences.}, } @article {pmid29915058, year = {2018}, author = {Ficici, E and Zhou, W and Castellano, S and Faraldo-Gómez, JD}, title = {Broadly conserved Na+-binding site in the N-lobe of prokaryotic multidrug MATE transporters.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6172-E6181}, pmid = {29915058}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Archaeal Proteins/*chemistry/genetics/metabolism ; Binding Sites ; Carrier Proteins/*chemistry/genetics/metabolism ; Pyrococcus furiosus/*chemistry/genetics/metabolism ; Structure-Activity Relationship ; }, abstract = {Multidrug and toxic-compound extrusion (MATE) proteins comprise an important but largely uncharacterized family of secondary-active transporters. In both eukaryotes and prokaryotes, these transporters protect the cell by catalyzing the efflux of a broad range of cytotoxic compounds, including human-made antibiotics and anticancer drugs. MATEs are thus potential pharmacological targets against drug-resistant pathogenic bacteria and tumor cells. The activity of MATEs is powered by transmembrane electrochemical ion gradients, but their molecular mechanism and ion specificity are not understood, in part because high-quality structural information is limited. Here, we use computational methods to study PfMATE, from Pyrococcus furiosus, whose structure is the best resolved to date. Analysis of available crystallographic data and additional molecular dynamics simulations unequivocally reveal an occupied Na+-binding site in the N-lobe of this transporter, which had not been previously recognized. We find this site to be selective against K+ and broadly conserved among prokaryotic MATEs, including homologs known to be Na+-dependent such as NorM-VC, VmrA, and ClbM, for which the location of the Na+ site had been debated. We note, however, that the chemical makeup of the proposed Na+ site indicates it is weakly specific against H+, explaining why MATEs featuring this Na+-binding motif may be solely driven by H+ in laboratory conditions. We further posit that the concurrent coupling to H+ and Na+ gradients observed for some Na+-driven MATEs owes to a second H+-binding site, within the C-lobe. In summary, our study provides insights into the structural basis for the complex ion dependency of MATE transporters.}, } @article {pmid29915057, year = {2018}, author = {Muffat, J and Li, Y and Omer, A and Durbin, A and Bosch, I and Bakiasi, G and Richards, E and Meyer, A and Gehrke, L and Jaenisch, R}, title = {Human induced pluripotent stem cell-derived glial cells and neural progenitors display divergent responses to Zika and dengue infections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7117-7122}, pmid = {29915057}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R37 HD045022/HD/NICHD NIH HHS/United States ; R33 AI100190/AI/NIAID NIH HHS/United States ; R37 CA084198/CA/NCI NIH HHS/United States ; R01 HD045022/HD/NICHD NIH HHS/United States ; R21 AI100190/AI/NIAID NIH HHS/United States ; }, mesh = {Female ; Humans ; Induced Pluripotent Stem Cells/*metabolism/pathology/virology ; Neural Stem Cells/*metabolism/pathology/virology ; Neuroglia/*metabolism/pathology/virology ; Pregnancy ; Pregnancy Complications, Infectious/*metabolism/pathology ; Zika Virus/*metabolism ; Zika Virus Infection/*metabolism/pathology ; }, abstract = {Maternal Zika virus (ZIKV) infection during pregnancy is recognized as the cause of an epidemic of microcephaly and other neurological anomalies in human fetuses. It remains unclear how ZIKV accesses the highly vulnerable population of neural progenitors of the fetal central nervous system (CNS), and which cell types of the CNS may be viral reservoirs. In contrast, the related dengue virus (DENV) does not elicit teratogenicity. To model viral interaction with cells of the fetal CNS in vitro, we investigated the tropism of ZIKV and DENV for different induced pluripotent stem cell-derived human cells, with a particular focus on microglia-like cells. We show that ZIKV infected isogenic neural progenitors, astrocytes, and microglia-like cells (pMGLs), but was only cytotoxic to neural progenitors. Infected glial cells propagated ZIKV and maintained ZIKV load over time, leading to viral spread to susceptible cells. DENV triggered stronger immune responses and could be cleared by neural and glial cells more efficiently. pMGLs, when cocultured with neural spheroids, invaded the tissue and, when infected with ZIKV, initiated neural infection. Since microglia derive from primitive macrophages originating in proximity to the maternal vasculature, they may act as a viral reservoir for ZIKV and establish infection of the fetal brain. Infection of immature neural stem cells by invading microglia may occur in the early stages of pregnancy, before angiogenesis in the brain rudiments. Our data are also consistent with ZIKV and DENV affecting the integrity of the blood-brain barrier, thus allowing infection of the brain later in life.}, } @article {pmid29915056, year = {2018}, author = {Maitra, A and Srivastava, P and Marchetti, MC and Lintuvuori, JS and Ramaswamy, S and Lenz, M}, title = {A nonequilibrium force can stabilize 2D active nematics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6934-6939}, pmid = {29915056}, issn = {1091-6490}, abstract = {Suspensions of actively driven anisotropic objects exhibit distinctively nonequilibrium behaviors, and current theories predict that they are incapable of sustaining orientational order at high activity. By contrast, here we show that nematic suspensions on a substrate can display order at arbitrarily high activity due to a previously unreported, potentially stabilizing active force. This force moreover emerges inevitably in theories of active orientable fluids under geometric confinement. The resulting nonequilibrium ordered phase displays robust giant number fluctuations that cannot be suppressed even by an incompressible solvent. Our results apply to virtually all experimental assays used to investigate the active nematic ordering of self-propelled colloids, bacterial suspensions, and the cytoskeleton and have testable implications in interpreting their nonequilibrium behaviors.}, } @article {pmid29915055, year = {2018}, author = {Hackenberg, C and Hakanpää, J and Cai, F and Antonyuk, S and Eigner, C and Meissner, S and Laitaoja, M and Jänis, J and Kerfeld, CA and Dittmann, E and Lamzin, VS}, title = {Structural and functional insights into the unique CBS-CP12 fusion protein family in cyanobacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7141-7146}, pmid = {29915055}, issn = {1091-6490}, mesh = {Bacterial Proteins/*genetics/metabolism ; Chloroplast Proteins/*genetics/metabolism ; Cystathionine beta-Synthase/*genetics/metabolism ; Microcystis/*genetics/metabolism ; *Multigene Family ; Protein Domains ; }, abstract = {Cyanobacteria are important photosynthetic organisms inhabiting a range of dynamic environments. This phylum is distinctive among photosynthetic organisms in containing genes encoding uncharacterized cystathionine β-synthase (CBS)-chloroplast protein (CP12) fusion proteins. These consist of two domains, each recognized as stand-alone photosynthetic regulators with different functions described in cyanobacteria (CP12) and plants (CP12 and CBSX). Here we show that CBS-CP12 fusion proteins are encoded in distinct gene neighborhoods, several unrelated to photosynthesis. Most frequently, CBS-CP12 genes are in a gene cluster with thioredoxin A (TrxA), which is prevalent in bloom-forming, marine symbiotic, and benthic mat cyanobacteria. Focusing on a CBS-CP12 from Microcystis aeruginosa PCC 7806 encoded in a gene cluster with TrxA, we reveal that the domain fusion led to the formation of a hexameric protein. We show that the CP12 domain is essential for hexamerization and contains an ordered, previously structurally uncharacterized N-terminal region. We provide evidence that CBS-CP12, while combining properties of both regulatory domains, behaves different from CP12 and plant CBSX. It does not form a ternary complex with phosphoribulokinase (PRK) and glyceraldehyde-3-phosphate dehydrogenase. Instead, CBS-CP12 decreases the activity of PRK in an AMP-dependent manner. We propose that the novel domain architecture and oligomeric state of CBS-CP12 expand its regulatory function beyond those of CP12 in cyanobacteria.}, } @article {pmid29915054, year = {2018}, author = {Yao, W and Wang, E and Bao, C and Zhang, Y and Zhang, K and Bao, K and Chan, CK and Chen, C and Avila, J and Asensio, MC and Zhu, J and Zhou, S}, title = {Quasicrystalline 30° twisted bilayer graphene as an incommensurate superlattice with strong interlayer coupling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6928-6933}, pmid = {29915054}, issn = {1091-6490}, abstract = {The interlayer coupling can be used to engineer the electronic structure of van der Waals heterostructures (superlattices) to obtain properties that are not possible in a single material. So far research in heterostructures has been focused on commensurate superlattices with a long-ranged Moiré period. Incommensurate heterostructures with rotational symmetry but not translational symmetry (in analogy to quasicrystals) are not only rare in nature, but also the interlayer interaction has often been assumed to be negligible due to the lack of phase coherence. Here we report the successful growth of quasicrystalline 30° twisted bilayer graphene (30°-tBLG), which is stabilized by the Pt(111) substrate, and reveal its electronic structure. The 30°-tBLG is confirmed by low energy electron diffraction and the intervalley double-resonance Raman mode at 1383 cm-1 Moreover, the emergence of mirrored Dirac cones inside the Brillouin zone of each graphene layer and a gap opening at the zone boundary suggest that these two graphene layers are coupled via a generalized Umklapp scattering mechanism-that is, scattering of a Dirac cone in one graphene layer by the reciprocal lattice vector of the other graphene layer. Our work highlights the important role of interlayer coupling in incommensurate quasicrystalline superlattices, thereby extending band structure engineering to incommensurate superstructures.}, } @article {pmid29915053, year = {2018}, author = {Negrón-Oyarzo, I and Espinosa, N and Aguilar-Rivera, M and Fuenzalida, M and Aboitiz, F and Fuentealba, P}, title = {Coordinated prefrontal-hippocampal activity and navigation strategy-related prefrontal firing during spatial memory formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7123-7128}, pmid = {29915053}, issn = {1091-6490}, support = {HIR 10-001/HX/HSRD VA/United States ; }, mesh = {Animals ; Gamma Rhythm/*physiology ; Hippocampus/cytology/*physiology ; Male ; Mice ; Neurons/cytology/*physiology ; Prefrontal Cortex/cytology/*physiology ; Spatial Memory/*physiology ; Spatial Navigation/*physiology ; }, abstract = {Learning the location of relevant places in the environment is crucial for survival. Such capacity is supported by a distributed network comprising the prefrontal cortex and hippocampus, yet it is not fully understood how these structures cooperate during spatial reference memory formation. Hence, we examined neural activity in the prefrontal-hippocampal circuit in mice during acquisition of spatial reference memory. We found that interregional oscillatory coupling increased with learning, specifically in the slow-gamma frequency (20 to 40 Hz) band during spatial navigation. In addition, mice used both spatial and nonspatial strategies to navigate and solve the task, yet prefrontal neuronal spiking and oscillatory phase coupling were selectively enhanced in the spatial navigation strategy. Lastly, a representation of the behavioral goal emerged in prefrontal spiking patterns exclusively in the spatial navigation strategy. These results suggest that reference memory formation is supported by enhanced cortical connectivity and evolving prefrontal spiking representations of behavioral goals.}, } @article {pmid29915052, year = {2018}, author = {Okunuki, Y and Mukai, R and Pearsall, EA and Klokman, G and Husain, D and Park, DH and Korobkina, E and Weiner, HL and Butovsky, O and Ksander, BR and Miller, JW and Connor, KM}, title = {Microglia inhibit photoreceptor cell death and regulate immune cell infiltration in response to retinal detachment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6264-E6273}, pmid = {29915052}, issn = {1091-6490}, support = {P30 EY014104/EY/NEI NIH HHS/United States ; R01 EY027303/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Cell Death/genetics/immunology ; Cell Survival/genetics/immunology ; Macrophages/*immunology/pathology ; Mice ; Mice, Transgenic ; Microglia/*immunology/pathology ; Photoreceptor Cells, Vertebrate/*immunology/pathology ; Receptors, Purinergic P2Y12/genetics/*immunology ; Retinal Detachment/genetics/*immunology/pathology ; }, abstract = {Retinal detachment (RD) is a sight-threatening complication common in many highly prevalent retinal disorders. RD rapidly leads to photoreceptor cell death beginning within 12 h following detachment. In patients with sustained RD, progressive visual decline due to photoreceptor cell death is common, leading to significant and permanent loss of vision. Microglia are the resident immune cells of the central nervous system, including the retina, and function in the homeostatic maintenance of the neuro-retinal microenvironment. It is known that microglia become activated and change their morphology in retinal diseases. However, the function of activated microglia in RD is incompletely understood, in part because of the lack of microglia-specific markers. Here, using the newly identified microglia marker P2ry12 and microglial depletion strategies, we demonstrate that retinal microglia are rapidly activated in response to RD and migrate into the injured area within 24 h post-RD, where they closely associate with infiltrating macrophages, a population distinct from microglia. Once in the injured photoreceptor layer, activated microglia can be observed to contain autofluorescence within their cell bodies, suggesting they function to phagocytose injured or dying photoreceptors. Depletion of retinal microglia results in increased disease severity and inhibition of macrophage infiltration, suggesting that microglia are involved in regulating neuroinflammation in the retina. Our work identifies that microglia mediate photoreceptor survival in RD and suggests that this effect may be due to microglial regulation of immune cells and photoreceptor phagocytosis.}, } @article {pmid29915051, year = {2018}, author = {Sonn, JY and Lee, J and Sung, MK and Ri, H and Choi, JK and Lim, C and Choe, J}, title = {Serine metabolism in the brain regulates starvation-induced sleep suppression in Drosophila melanogaster.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7129-7134}, pmid = {29915051}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal ; Brain/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; L-Serine Dehydratase/genetics/*metabolism ; *Mutation ; Serine/genetics/*metabolism ; *Signal Transduction ; Starvation/genetics/*metabolism ; }, abstract = {Sleep and metabolism are physiologically and behaviorally intertwined; however, the molecular basis for their interaction remains poorly understood. Here, we identified a serine metabolic pathway as a key mediator for starvation-induced sleep suppression. Transcriptome analyses revealed that enzymes involved in serine biosynthesis were induced upon starvation in Drosophila melanogaster brains. Genetic mutants of astray (aay), a fly homolog of the rate-limiting phosphoserine phosphatase in serine biosynthesis, displayed reduced starvation-induced sleep suppression. In contrast, a hypomorphic mutation in a serine/threonine-metabolizing enzyme, serine/threonine dehydratase (stdh), exaggerated starvation-induced sleep suppression. Analyses of double mutants indicated that aay and stdh act on the same genetic pathway to titrate serine levels in the head as well as to adjust starvation-induced sleep behaviors. RNA interference-mediated depletion of aay expression in neurons, using cholinergic Gal4 drivers, phenocopied aay mutants, while a nicotinic acetylcholine receptor antagonist selectively rescued the exaggerated starvation-induced sleep suppression in stdh mutants. Taken together, these data demonstrate that neural serine metabolism controls sleep during starvation, possibly via cholinergic signaling. We propose that animals have evolved a sleep-regulatory mechanism that reprograms amino acid metabolism for adaptive sleep behaviors in response to metabolic needs.}, } @article {pmid29915050, year = {2018}, author = {Zhang, R and LaFrance, B and Nogales, E}, title = {Separating the effects of nucleotide and EB binding on microtubule structure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6191-E6200}, pmid = {29915050}, issn = {1091-6490}, support = {P01 GM051487/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Humans ; Microtubule-Associated Proteins/*chemistry/metabolism ; Microtubules/*chemistry/metabolism/ultrastructure ; *Molecular Dynamics Simulation ; }, abstract = {Microtubules (MTs) are polymers assembled from αβ-tubulin heterodimers that display the hallmark behavior of dynamic instability. MT dynamics are driven by GTP hydrolysis within the MT lattice, and are highly regulated by a number of MT-associated proteins (MAPs). How MAPs affect MTs is still not fully understood, partly due to a lack of high-resolution structural data on undecorated MTs, which need to serve as a baseline for further comparisons. Here we report three structures of MTs in different nucleotide states (GMPCPP, GDP, and GTPγS) at near-atomic resolution and in the absence of any binding proteins. These structures allowed us to differentiate the effects of nucleotide state versus MAP binding on MT structure. Kinesin binding has a small effect on the extended, GMPCPP-bound lattice, but hardly affects the compacted GDP-MT lattice, while binding of end-binding (EB) proteins can induce lattice compaction (together with lattice twist) in MTs that were initially in an extended and more stable state. We propose a MT lattice-centric model in which the MT lattice serves as a platform that integrates internal tubulin signals, such as nucleotide state, with outside signals, such as binding of MAPs or mechanical forces, resulting in global lattice rearrangements that in turn affect the affinity of other MT partners and result in the exquisite regulation of MT dynamics.}, } @article {pmid29915049, year = {2018}, author = {Fast, D and Kostiuk, B and Foley, E and Pukatzki, S}, title = {Commensal pathogen competition impacts host viability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7099-7104}, pmid = {29915049}, issn = {1091-6490}, support = {MOP 7746//CIHR/Canada ; MOP 137106//CIHR/Canada ; }, mesh = {Acetobacter/genetics/*metabolism ; Animals ; Bacterial Proteins/genetics/*metabolism ; Cholera/genetics/*metabolism/microbiology ; Disease Models, Animal ; Drosophila melanogaster ; Type VI Secretion Systems/genetics/*metabolism ; Vibrio cholerae/genetics/*metabolism ; }, abstract = {While the structure and regulatory networks that govern type-six secretion system (T6SS) activity of Vibrio cholerae are becoming increasingly clear, we know less about the role of T6SS in disease. Under laboratory conditions, V. cholerae uses T6SS to outcompete many Gram-negative species, including other V. cholerae strains and human commensal bacteria. However, the role of these interactions has not been resolved in an in vivo setting. We used the Drosophila melanogaster model of cholera to define the contribution of T6SS to V. cholerae pathogenesis. Here, we demonstrate that interactions between T6SS and host commensals impact pathogenesis. Inactivation of T6SS, or removal of commensal bacteria, attenuates disease severity. Reintroduction of the commensal, Acetobacter pasteurianus, into a germ-free host is sufficient to restore T6SS-dependent pathogenesis in which T6SS and host immune responses regulate viability. Together, our data demonstrate that T6SS acts on commensal bacteria to promote the pathogenesis of V. cholerae.}, } @article {pmid29915048, year = {2018}, author = {Hosseini, SR and Wagner, A}, title = {Genomic organization underlying deletional robustness in bacterial metabolic systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7075-7080}, pmid = {29915048}, issn = {1091-6490}, mesh = {Bacteria/*genetics/*metabolism ; *Evolution, Molecular ; *Gene Deletion ; *Genome, Bacterial ; *Multigene Family ; }, abstract = {Large-scale DNA deletions and gene loss are pervasive in bacterial genomes. This observation raises the possibility that evolutionary adaptation has altered bacterial genome organization to increase its robustness to large-scale tandem gene deletions. To find out, we systematically analyzed 55 bacterial genome-scale metabolisms and showed that metabolic gene ordering renders an organism's viability in multiple nutrient environments significantly more robust against tandem multigene deletions than expected by chance. This excess robustness is caused by multiple factors, which include the clustering of essential metabolic genes, a greater-than-expected distance of synthetically lethal metabolic gene pairs, and the clustering of nonessential metabolic genes. By computationally creating minimal genomes, we show that a nonadaptive origin of such clustering could in principle arise as a passive byproduct of bacterial genome growth. However, because genome randomization forces such as translocation and inversion would eventually erode such clustering, adaptive processes are necessary to sustain it. We provide evidence suggesting that this organization might result from adaptation to ongoing gene deletions, and from selective advantages associated with coregulating functionally related genes. Horizontal gene transfer in the presence of gene deletions contributes to sustaining the clustering of essential genes. In sum, our observations suggest that the genome organization of bacteria is driven by adaptive processes that provide phenotypic robustness in response to large-scale gene deletions. This robustness may be especially important for bacterial populations that take advantage of gene loss to adapt to new environments.}, } @article {pmid29915047, year = {2018}, author = {Töpperwien, M and van der Meer, F and Stadelmann, C and Salditt, T}, title = {Three-dimensional virtual histology of human cerebellum by X-ray phase-contrast tomography.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6940-6945}, pmid = {29915047}, issn = {1091-6490}, mesh = {Cerebellum/*cytology/*diagnostic imaging ; Female ; *Histology ; Humans ; *Imaging, Three-Dimensional ; Male ; *Tomography, X-Ray Computed ; }, abstract = {To quantitatively evaluate brain tissue and its corresponding function, knowledge of the 3D cellular distribution is essential. The gold standard to obtain this information is histology, a destructive and labor-intensive technique where the specimen is sliced and examined under a light microscope, providing 3D information at nonisotropic resolution. To overcome the limitations of conventional histology, we use phase-contrast X-ray tomography with optimized optics, reconstruction, and image analysis, both at a dedicated synchrotron radiation endstation, which we have equipped with X-ray waveguide optics for coherence and wavefront filtering, and at a compact laboratory source. As a proof-of-concept demonstration we probe the 3D cytoarchitecture in millimeter-sized punches of unstained human cerebellum embedded in paraffin and show that isotropic subcellular resolution can be reached at both setups throughout the specimen. To enable a quantitative analysis of the reconstructed data, we demonstrate automatic cell segmentation and localization of over 1 million neurons within the cerebellar cortex. This allows for the analysis of the spatial organization and correlation of cells in all dimensions by borrowing concepts from condensed-matter physics, indicating a strong short-range order and local clustering of the cells in the granular layer. By quantification of 3D neuronal "packing," we can hence shed light on how the human cerebellum accommodates 80% of the total neurons in the brain in only 10% of its volume. In addition, we show that the distribution of neighboring neurons in the granular layer is anisotropic with respect to the Purkinje cell dendrites.}, } @article {pmid29915046, year = {2018}, author = {Kwon, S and Watanabe, S and Nishitani, Y and Kawashima, T and Kanai, T and Atomi, H and Miki, K}, title = {Crystal structures of a [NiFe] hydrogenase large subunit HyhL in an immature state in complex with a Ni chaperone HypA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7045-7050}, pmid = {29915046}, issn = {1091-6490}, mesh = {Archaeal Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Hydrogenase/*chemistry/genetics/metabolism ; Molecular Chaperones/*chemistry/genetics/metabolism ; Multiprotein Complexes/*chemistry/genetics/metabolism ; Protein Structure, Quaternary ; Protein Subunits/*chemistry/genetics/metabolism ; Thermococcus/*chemistry/genetics/metabolism ; }, abstract = {Ni-Fe clusters are inserted into the large subunit of [NiFe] hydrogenases by maturation proteins such as the Ni chaperone HypA via an unknown mechanism. We determined crystal structures of an immature large subunit HyhL complexed with HypA from Thermococcus kodakarensis Structure analysis revealed that the N-terminal region of HyhL extends outwards and interacts with the Ni-binding domain of HypA. Intriguingly, the C-terminal extension of immature HyhL, which is cleaved in the mature form, adopts a β-strand adjacent to its N-terminal β-strands. The position of the C-terminal extension corresponds to that of the N-terminal extension of a mature large subunit, preventing the access of endopeptidases to the cleavage site of HyhL. These findings suggest that Ni insertion into the active site induces spatial rearrangement of both the N- and C-terminal tails of HyhL, which function as a key checkpoint for the completion of the Ni-Fe cluster assembly.}, } @article {pmid29915045, year = {2018}, author = {Rothbard, JB and Rothbard, JJ and Soares, L and Fathman, CG and Steinman, L}, title = {Identification of a common immune regulatory pathway induced by small heat shock proteins, amyloid fibrils, and nicotine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7081-7086}, pmid = {29915045}, issn = {1091-6490}, support = {S10 OD010580/OD/NIH HHS/United States ; S10 RR025518/RR/NCRR NIH HHS/United States ; }, mesh = {Amyloid/*immunology ; Animals ; B-Lymphocytes/immunology/pathology ; Encephalomyelitis, Autoimmune, Experimental/*immunology/pathology ; Heat-Shock Proteins/*immunology ; Humans ; Immune Tolerance ; Macrophages, Peritoneal/*immunology/pathology ; Mice ; Nicotine/*immunology ; alpha7 Nicotinic Acetylcholine Receptor/*immunology ; }, abstract = {Although certain dogma portrays amyloid fibrils as drivers of neurodegenerative disease and neuroinflammation, we have found, paradoxically, that amyloid fibrils and small heat shock proteins (sHsps) are therapeutic in experimental autoimmune encephalomyelitis (EAE). They reduce clinical paralysis and induce immunosuppressive pathways, diminishing inflammation. A key question was the identification of the target for these molecules. When sHsps and amyloid fibrils were chemically cross-linked to immune cells, a limited number of proteins were precipitated, including the α7 nicotinic acetylcholine receptor (α7 NAChR). The α7 NAChR is noteworthy among the over 20 known receptors for amyloid fibrils, because it plays a central role in a well-defined immune-suppressive pathway. Competitive binding between amyloid fibrils and α-bungarotoxin to peritoneal macrophages (MΦs) confirmed the involvement of α7 NAChR. The mechanism of immune suppression was explored, and, similar to nicotine, amyloid fibrils inhibited LPS induction of a common set of inflammatory cytokines while inducing Stat3 signaling and autophagy. Consistent with this, previous studies have established that nicotine, sHsps, and amyloid fibrils all were effective therapeutics in EAE. Interestingly, B lymphocytes were needed for the therapeutic effect. These results suggest that agonists of α7 NAChR might have therapeutic benefit for a variety of inflammatory diseases.}, } @article {pmid29915044, year = {2018}, author = {Sato, T and Chang, HC and Bayeva, M and Shapiro, JS and Ramos-Alonso, L and Kouzu, H and Jiang, X and Liu, T and Yar, S and Sawicki, KT and Chen, C and Martínez-Pastor, MT and Stumpo, DJ and Schumacker, PT and Blackshear, PJ and Ben-Sahra, I and Puig, S and Ardehali, H}, title = {mRNA-binding protein tristetraprolin is essential for cardiac response to iron deficiency by regulating mitochondrial function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6291-E6300}, pmid = {29915044}, issn = {1091-6490}, support = {R01 HL140973/HL/NHLBI NIH HHS/United States ; R01 HL138982/HL/NHLBI NIH HHS/United States ; R01 HL127646/HL/NHLBI NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; T32 GM008152/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Electron Transport Complex III/genetics/metabolism ; Iron/*deficiency ; Iron-Sulfur Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Mitochondria, Heart/enzymology/*metabolism ; Myocardium/*metabolism ; NADH Dehydrogenase/genetics/*metabolism ; Oxidation-Reduction ; Tristetraprolin/genetics/*metabolism ; }, abstract = {Cells respond to iron deficiency by activating iron-regulatory proteins to increase cellular iron uptake and availability. However, it is not clear how cells adapt to conditions when cellular iron uptake does not fully match iron demand. Here, we show that the mRNA-binding protein tristetraprolin (TTP) is induced by iron deficiency and degrades mRNAs of mitochondrial Fe/S-cluster-containing proteins, specifically Ndufs1 in complex I and Uqcrfs1 in complex III, to match the decrease in Fe/S-cluster availability. In the absence of TTP, Uqcrfs1 levels are not decreased in iron deficiency, resulting in nonfunctional complex III, electron leakage, and oxidative damage. Mice with deletion of Ttp display cardiac dysfunction with iron deficiency, demonstrating that TTP is necessary for maintaining cardiac function in the setting of low cellular iron. Altogether, our results describe a pathway that is activated in iron deficiency to regulate mitochondrial function to match the availability of Fe/S clusters.}, } @article {pmid29915043, year = {2018}, author = {Claxton, DP and Jagessar, KL and Steed, PR and Stein, RA and Mchaourab, HS}, title = {Sodium and proton coupling in the conformational cycle of a MATE antiporter from Vibrio cholerae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6182-E6190}, pmid = {29915043}, issn = {1091-6490}, support = {R01 GM077659/GM/NIGMS NIH HHS/United States ; }, mesh = {Antiporters/*chemistry/genetics/metabolism ; Bacterial Proteins/*chemistry/genetics/metabolism ; Doxorubicin/*chemistry/metabolism ; Protein Domains ; *Protons ; Sodium/*chemistry/metabolism ; Vibrio cholerae/*chemistry/genetics/metabolism ; }, abstract = {Secondary active transporters belonging to the multidrug and toxic compound extrusion (MATE) family harness the potential energy of electrochemical ion gradients to export a broad spectrum of cytotoxic compounds, thus contributing to multidrug resistance. The current mechanistic understanding of ion-coupled substrate transport has been informed by a limited set of MATE transporter crystal structures from multiple organisms that capture a 12-transmembrane helix topology adopting similar outward-facing conformations. Although these structures mapped conserved residues important for function, the mechanistic role of these residues in shaping the conformational cycle has not been investigated. Here, we use double-electron electron resonance (DEER) spectroscopy to explore ligand-dependent conformational changes of NorM from Vibrio cholerae (NorM-Vc), a MATE transporter proposed to be coupled to both Na+ and H+ gradients. Distance measurements between spin labels on the periplasmic side of NorM-Vc identified unique structural intermediates induced by binding of Na+, H+, or the substrate doxorubicin. The Na+- and H+-dependent intermediates were associated with distinct conformations of TM1. Site-directed mutagenesis of conserved residues revealed that Na+- and H+-driven conformational changes are facilitated by a network of polar residues in the N-terminal domain cavity, whereas conserved carboxylates buried in the C-terminal domain are critical for stabilizing the drug-bound state. Interpreted in conjunction with doxorubicin binding of mutant NorM-Vc and cell toxicity assays, these results establish the role of ion-coupled conformational dynamics in the functional cycle and implicate H+ in the doxorubicin release mechanism.}, } @article {pmid29915042, year = {2018}, author = {Gannon, WJ and Wu, LS and Zaliznyak, IA and Xu, WH and Tsvelik, AM and Qiu, Y and Rodriguez-Rivera, JA and Aronson, MC}, title = {Local quantum phase transition in YFe2Al10.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6995-6999}, pmid = {29915042}, issn = {1091-6490}, abstract = {A phase transition occurs when correlated regions of a new phase grow to span the system and the fluctuations within the correlated regions become long lived. Here, we present neutron scattering measurements showing that this conventional picture must be replaced in YFe2Al10, a compound that forms naturally very close to a [Formula: see text] quantum phase transition. Fully quantum mechanical fluctuations of localized moments are found to diverge at low energies and temperatures; however, the fluctuating moments are entirely without spatial correlations. Zero temperature order in YFe2Al10 is achieved by an entirely local type of quantum phase transition that may originate with the creation of the moments themselves.}, } @article {pmid29915041, year = {2018}, author = {Cohen, Y and Ronen, Y and Kang, JH and Heiblum, M and Feinberg, D and Mélin, R and Shtrikman, H}, title = {Nonlocal supercurrent of quartets in a three-terminal Josephson junction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6991-6994}, pmid = {29915041}, issn = {1091-6490}, abstract = {A novel nonlocal supercurrent, carried by quartets, each consisting of four electrons, is expected to appear in a voltage-biased three-terminal Josephson junction. This supercurrent results from a nonlocal Andreev bound state (ABS), formed among three superconducting terminals. While in a two-terminal Josephson junction the usual ABS, and thus the dc Josephson current, exists only in equilibrium, the ABS, which gives rise to the quartet supercurrent, persists in the nonlinear regime. In this work, we report such resonance in a highly coherent three-terminal Josephson junction made in an InAs nanowire in proximity to an aluminum superconductor. In addition to nonlocal conductance measurements, cross-correlation measurements of current fluctuations provided a distinctive signature of the quartet supercurrent. Multiple device geometries had been tested, allowing us to rule out competing mechanisms and to establish the underlying microscopic origin of this coherent nondissipative current.}, } @article {pmid29915040, year = {2018}, author = {Haigler, CH}, title = {Two types of cellulose synthesis complex knit the plant cell wall together.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6882-6884}, pmid = {29915040}, issn = {1091-6490}, mesh = {Arabidopsis ; *Cell Wall ; Cellulose ; Gene Expression Regulation, Plant ; Glucosyltransferases ; *Plant Cells ; }, } @article {pmid29915039, year = {2018}, author = {Seo, BA and Cho, T and Lee, DZ and Lee, JJ and Lee, B and Kim, SW and Shin, HS and Kang, MG}, title = {LARGE, an intellectual disability-associated protein, regulates AMPA-type glutamate receptor trafficking and memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7111-7116}, pmid = {29915039}, issn = {1091-6490}, mesh = {Animals ; Hippocampus/cytology/*metabolism ; Humans ; Long-Term Potentiation/*physiology ; Memory/*physiology ; Mice ; N-Acetylglucosaminyltransferases/genetics/*metabolism ; Protein Transport/physiology ; Receptors, AMPA/genetics/*metabolism ; }, abstract = {Mutations in the human LARGE gene result in severe intellectual disability and muscular dystrophy. How LARGE mutation leads to intellectual disability, however, is unclear. In our proteomic study, LARGE was found to be a component of the AMPA-type glutamate receptor (AMPA-R) protein complex, a main player for learning and memory in the brain. Here, our functional study of LARGE showed that LARGE at the Golgi apparatus (Golgi) negatively controlled AMPA-R trafficking from the Golgi to the plasma membrane, leading to down-regulated surface and synaptic AMPA-R targeting. In LARGE knockdown mice, long-term potentiation (LTP) was occluded by synaptic AMPA-R overloading, resulting in impaired contextual fear memory. These findings indicate that the fine-tuning of AMPA-R trafficking by LARGE at the Golgi is critical for hippocampus-dependent memory in the brain. Our study thus provides insights into the pathophysiology underlying cognitive deficits in brain disorders associated with intellectual disability.}, } @article {pmid29915038, year = {2018}, author = {}, title = {Correction to Supporting Information for Zheng et al., How electrostatic networks modulate specificity and stability of collagen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6098}, doi = {10.1073/pnas.1809680115}, pmid = {29915038}, issn = {1091-6490}, } @article {pmid29915037, year = {2018}, author = {Skorobogatko, Y and Dragan, M and Cordon, C and Reilly, SM and Hung, CW and Xia, W and Zhao, P and Wallace, M and Lackey, DE and Chen, XW and Osborn, O and Bogner-Strauss, JG and Theodorescu, D and Metallo, CM and Olefsky, JM and Saltiel, AR}, title = {RalA controls glucose homeostasis by regulating glucose uptake in brown fat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {30}, pages = {7819-7824}, pmid = {29915037}, issn = {1091-6490}, support = {R01 DK076906/DK/NIDDK NIH HHS/United States ; R01 DK061618/DK/NIDDK NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; K01 DK105075/DK/NIDDK NIH HHS/United States ; R01 DK060591/DK/NIDDK NIH HHS/United States ; }, mesh = {3T3-L1 Cells ; Adipose Tissue, Brown/*metabolism/pathology ; Animals ; GTPase-Activating Proteins/genetics/metabolism ; Gene Deletion ; Glucose/genetics/*metabolism ; Glucose Transporter Type 4/genetics/metabolism ; *Homeostasis ; Mice ; Mice, Knockout ; ral GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {Insulin increases glucose uptake into adipose tissue and muscle by increasing trafficking of the glucose transporter Glut4. In cultured adipocytes, the exocytosis of Glut4 relies on activation of the small G protein RalA by insulin, via inhibition of its GTPase activating complex RalGAP. Here, we evaluate the role of RalA in glucose uptake in vivo with specific chemical inhibitors and by generation of mice with adipocyte-specific knockout of RalGAPB. RalA was profoundly activated in brown adipose tissue after feeding, and its inhibition prevented Glut4 exocytosis. RalGAPB knockout mice with diet-induced obesity were protected from the development of metabolic disease due to increased glucose uptake into brown fat. Thus, RalA plays a crucial role in glucose transport in adipose tissue in vivo.}, } @article {pmid29915036, year = {2018}, author = {Ma, Y and Zhao, J and Li, Y and Li, D and Chen, L and Liu, J and Dann, SJD and Ma, Y and Yang, X and Ge, Z and Sheng, Z and Zhang, J}, title = {Ultrahigh-charge electron beams from laser-irradiated solid surface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6980-6985}, pmid = {29915036}, issn = {1091-6490}, abstract = {Compact acceleration of a tightly collimated relativistic electron beam with high charge from a laser-plasma interaction has many unique applications. However, currently the well-known schemes, including laser wakefield acceleration from gases and vacuum laser acceleration from solids, often produce electron beams either with low charge or with large divergence angles. In this work, we report the generation of highly collimated electron beams with a divergence angle of a few degrees, nonthermal spectra peaked at the megaelectronvolt level, and extremely high charge (∼100 nC) via a powerful subpicosecond laser pulse interacting with a solid target in grazing incidence. Particle-in-cell simulations illustrate a direct laser acceleration scenario, in which the self-filamentation is triggered in a large-scale near-critical-density plasma and electron bunches are accelerated periodically and collimated by the ultraintense electromagnetic field. The energy density of such electron beams in high-Z materials reaches to [Formula: see text], making it a promising tool to drive warm or even hot dense matter states.}, } @article {pmid29915035, year = {2018}, author = {Yan, Q and Lu, Y and Zhou, L and Chen, J and Xu, H and Cai, M and Shi, Y and Jiang, J and Xiong, W and Gao, J and Wang, H}, title = {Mechanistic insights into GLUT1 activation and clustering revealed by super-resolution imaging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7033-7038}, pmid = {29915035}, issn = {1091-6490}, mesh = {Cytoskeleton ; Glucose Transporter Type 1/chemistry/*metabolism ; Glycosylation ; HeLa Cells ; Humans ; Membrane Microdomains/chemistry/*metabolism ; Microscopy ; }, abstract = {The glucose transporter GLUT1, a plasma membrane protein that mediates glucose homeostasis in mammalian cells, is responsible for constitutive uptake of glucose into many tissues and organs. Many studies have focused on its vital physiological functions and close relationship with diseases. However, the molecular mechanisms of its activation and transport are not clear, and its detailed distribution pattern on cell membranes also remains unknown. To address these, we first investigated the distribution and assembly of GLUT1 at a nanometer resolution by super-resolution imaging. On HeLa cell membranes, the transporter formed clusters with an average diameter of ∼250 nm, the majority of which were regulated by lipid rafts, as well as being restricted in size by both the cytoskeleton and glycosylation. More importantly, we found that the activation of GLUT1 by azide or MβCD did not increase its membrane expression but induced the decrease of the large clusters. The results suggested that sporadic distribution of GLUT1 may facilitate the transport of glucose, implying a potential association between the distribution and activation. Collectively, our work characterized the clustering distribution of GLUT1 and linked its spatial structural organization to the functions, which would provide insights into the activation mechanism of the transporter.}, } @article {pmid29915034, year = {2018}, author = {Sweis, BM and Larson, EB and Redish, AD and Thomas, MJ}, title = {Altering gain of the infralimbic-to-accumbens shell circuit alters economically dissociable decision-making algorithms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6347-E6355}, pmid = {29915034}, issn = {1091-6490}, support = {R01 MH112688/MH/NIMH NIH HHS/United States ; R01 DA005208/DA/NIDA NIH HHS/United States ; R01 DA019666/DA/NIDA NIH HHS/United States ; F30 DA043326/DA/NIDA NIH HHS/United States ; R01 DA030672/DA/NIDA NIH HHS/United States ; T32 GM008471/GM/NIGMS NIH HHS/United States ; R01 MH080318/MH/NIMH NIH HHS/United States ; T32 GM008244/GM/NIGMS NIH HHS/United States ; K02 DA035459/DA/NIDA NIH HHS/United States ; }, mesh = {*Algorithms ; Animals ; Decision Making/*physiology ; Limbic System/cytology/*physiology ; Male ; Mice ; Nucleus Accumbens/cytology/*physiology ; Synapses/*physiology ; Synaptic Transmission/*physiology ; }, abstract = {The nucleus accumbens shell (NAcSh) is involved in reward valuation. Excitatory projections from infralimbic cortex (IL) to NAcSh undergo synaptic remodeling in rodent models of addiction and enable the extinction of disadvantageous behaviors. However, how the strength of synaptic transmission of the IL-NAcSh circuit affects decision-making information processing and reward valuation remains unknown, particularly because these processes can conflict within a given trial and particularly given recent data suggesting that decisions arise from separable information-processing algorithms. The approach of many neuromodulation studies is to disrupt information flow during on-going behaviors; however, this limits the interpretation of endogenous encoding of computational processes. Furthermore, many studies are limited by the use of simple behavioral tests of value which are unable to dissociate neurally distinct decision-making algorithms. We optogenetically altered the strength of synaptic transmission between glutamatergic IL-NAcSh projections in mice trained on a neuroeconomic task capable of separating multiple valuation processes. We found that induction of long-term depression in these synapses produced lasting changes in foraging processes without disrupting deliberative processes. Mice displayed inflated reevaluations to stay when deciding whether to abandon continued reward-seeking investments but displayed no changes during initial commitment decisions. We also developed an ensemble-level measure of circuit-specific plasticity that revealed individual differences in foraging valuation tendencies. Our results demonstrate that alterations in projection-specific synaptic strength between the IL and the NAcSh are capable of augmenting self-control economic valuations within a particular decision-making modality and suggest that the valuation mechanisms for these multiple decision-making modalities arise from different circuits.}, } @article {pmid29915033, year = {2018}, author = {Barth-Naftilan, E and Sohng, J and Saiers, JE}, title = {Methane in groundwater before, during, and after hydraulic fracturing of the Marcellus Shale.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6970-6975}, pmid = {29915033}, issn = {1091-6490}, abstract = {Concern persists over the potential for unconventional oil and gas development to contaminate groundwater with methane and other chemicals. These concerns motivated our 2-year prospective study of groundwater quality within the Marcellus Shale. We installed eight multilevel monitoring wells within bedrock aquifers of a 25-km2 area targeted for shale gas development (SGD). Twenty-four isolated intervals within these wells were sampled monthly over 2 years and groundwater pressures were recorded before, during, and after seven shale gas wells were drilled, hydraulically fractured, and placed into production. Perturbations in groundwater pressures were detected at hilltop monitoring wells during drilling of nearby gas wells and during a gas well casing breach. In both instances, pressure changes were ephemeral (<24 hours) and no lasting impact on groundwater quality was observed. Overall, methane concentrations ([CH4]) ranged from detection limit to 70 mg/L, increased with aquifer depth, and, at several sites, exhibited considerable temporal variability. Methane concentrations in valley monitoring wells located above gas well laterals increased in conjunction with SGD, but CH4 isotopic composition and hydrocarbon composition (CH4/C2H6) are inconsistent with Marcellus origins for this gas. Further, salinity increased concurrently with [CH4], which rules out contamination by gas phase migration of fugitive methane from structurally compromised gas wells. Collectively, our observations suggest that SGD was an unlikely source of methane in our valley wells, and that naturally occurring methane in valley settings, where regional flow systems interact with local flow systems, is more variable in concentration and composition both temporally and spatially than previously understood.}, } @article {pmid29915032, year = {2018}, author = {Ramirez Rozzi, FV}, title = {Reproduction in the Baka pygmies and drop in their fertility with the arrival of alcohol.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6126-E6134}, pmid = {29915032}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; *African Continental Ancestry Group ; Alcoholic Beverages/*adverse effects ; Alcoholism/*mortality ; Cameroon/epidemiology ; Child ; *Child Mortality ; Child, Preschool ; Female ; *Fertility ; Humans ; Infant ; *Infant Mortality ; Male ; }, abstract = {To understand the diversity of human growth and development from an evolutionary point of view, there is an urgent need to characterize the life-history variables of vanishing forager societies. The small body size of the Baka pygmies is the outcome of a low growth rate during infancy. While the ages at sexual maturity, menarche, and first delivery are similar to those in other populations, fertility aspects are unknown. In the Le Bosquet district in Cameroon, thanks to systematic birth records kept from 1980 onwards, we were able to assign ages to individuals with certainty. This study, based on chronological records and on data collected from 2007 to 2017, presents life-history variables related to fertility and mortality among the Baka pygmies: total fertility rate, age-specific fertility rate, completed family size, reproductive span, age at menopause, and infant and juvenile mortality. The Baka present low infant and juvenile mortality, and their fertility pattern differs from that of other forager societies in the higher age-specific fertility rates found in the two lower age classes. Future studies will need to assess whether this particular pattern and the short interbirth interval are related to highly cooperative childrearing, which in the Baka is associated with slow growth. The fertility rate has fallen drastically since 2011, and this matches the arrival of cheap alcohol in the community. Our data provide a first-hand record of the impact of alcohol on fertility in a hunter-gatherer society which appears to be seriously compromising the survival of the Baka.}, } @article {pmid29915031, year = {2018}, author = {Sun, X and Dyson, HJ and Wright, PE}, title = {Kinetic analysis of the multistep aggregation pathway of human transthyretin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6201-E6208}, pmid = {29915031}, issn = {1091-6490}, support = {17POST32810003//American Heart Association-American Stroke Association/United States ; R01 DK034909/DK/NIDDK NIH HHS/United States ; R37 DK034909/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Cardiomyopathies/genetics/metabolism/pathology ; Humans ; *Mutation, Missense ; Nuclear Magnetic Resonance, Biomolecular ; Prealbumin/*chemistry/genetics/metabolism ; *Protein Aggregation, Pathological ; *Protein Multimerization ; Protein Structure, Quaternary ; }, abstract = {Aggregation of transthyretin (TTR) is the causative agent for TTR cardiomyopathy and polyneuropathy amyloidoses. Aggregation is initiated by dissociation of the TTR tetramer into a monomeric intermediate, which self-assembles into amyloid. The coupled multiple-step equilibria and low-concentration, aggregation-prone intermediates are challenging to probe using conventional assays. We report a 19F-NMR assay that leverages a highly sensitive trifluoroacetyl probe at a strategic site that gives distinct 19F chemical shifts for the TTR tetramer and monomeric intermediate and enables direct quantification of their populations during the aggregation process. Integration of real-time 19F-NMR and turbidity measurements as a function of temperature allows kinetic and mechanistic dissection of the aggregation pathway of both wild-type and mutant TTR. At physiological temperature, the monomeric intermediate formed by wild-type TTR under mildly acidic conditions rapidly aggregates into species that are invisible to NMR, leading to loss of the NMR signal at the same rate as the turbidity increase. Lower temperature accelerates tetramer dissociation and decelerates monomer tetramerization and oligomerization via reduced hydrophobic interactions associated with packing of a phenylalanine (F87) into a neighboring protomer. As a result, the intermediate accumulates to a higher level, and formation of higher-order aggregates is delayed. Application of this assay to pathogenic (V30M, L55P, and V122I) and protective (T119M) mutants revealed significant differences in behavior. A monomeric intermediate was observed only for V122I: aggregation of V30M and L55P proceeds without an observable monomeric intermediate, whereas the protective mutant T119M remains resistant to tetramer dissociation and aggregation.}, } @article {pmid29915030, year = {2018}, author = {Young, M and Dahoun, T and Sokrat, B and Arber, C and Chen, KM and Bouvier, M and Barth, P}, title = {Computational design of orthogonal membrane receptor-effector switches for rewiring signaling pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7051-7056}, pmid = {29915030}, issn = {1091-6490}, support = {R01 GM097207/GM/NIGMS NIH HHS/United States ; T32 GM008280/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Line ; *Computer Simulation ; GTP-Binding Protein alpha Subunits, Gi-Go/*chemistry/genetics ; Humans ; Multiprotein Complexes/*chemistry/genetics ; *Protein Engineering ; Receptors, Dopamine D2/*chemistry/genetics ; *Signal Transduction ; }, abstract = {Membrane receptors regulate numerous intracellular functions. However, the molecular underpinnings remain poorly understood because most receptors initiate multiple signaling pathways through distinct interaction interfaces that are structurally uncharacterized. We present an integrated computational and experimental approach to model and rationally engineer membrane receptor-intracellular protein systems signaling with novel pathway selectivity. We targeted the dopamine D2 receptor (D2), a G-protein-coupled receptor (GPCR), which primarily signals through Gi, but triggers also the Gq and beta-arrestin pathways. Using this approach, we designed orthogonal D2-Gi complexes, which coupled with high specificity and triggered exclusively the Gi-dependent signaling pathway. We also engineered an orthogonal chimeric D2-Gs/i complex that rewired D2 signaling from a Gi-mediated inhibitory into a Gs-dependent activating pathway. Reinterpreting the evolutionary history of GPCRs in light of the designed proteins, we uncovered an unforeseen hierarchical code of GPCR-G-protein coupling selectivity determinants. The results demonstrate that membrane receptor-cytosolic protein systems can be rationally engineered to regulate mammalian cellular functions. The method should prove useful for creating orthogonal molecular switches that redirect signals at the cell surface for cell-engineering applications.}, } @article {pmid29915029, year = {2018}, author = {Lee, JJ and van de Ven, RAH and Zaganjor, E and Ng, MR and Barakat, A and Demmers, JJPG and Finley, LWS and Gonzalez Herrera, KN and Hung, YP and Harris, IS and Jeong, SM and Danuser, G and McAllister, SS and Haigis, MC}, title = {Inhibition of epithelial cell migration and Src/FAK signaling by SIRT3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7057-7062}, pmid = {29915029}, issn = {1091-6490}, support = {R01 CA166284/CA/NCI NIH HHS/United States ; R01 CA213062/CA/NCI NIH HHS/United States ; R01 DK103295/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Breast Neoplasms/*metabolism/pathology ; Cell Line, Tumor ; *Cell Movement ; Enzyme Activation ; Epithelial Cells/*metabolism/pathology ; Female ; Focal Adhesion Kinase 1/*metabolism ; Humans ; Neoplasm Metastasis ; Neoplasm Proteins/*metabolism ; Reactive Oxygen Species ; Sirtuin 3/*biosynthesis/metabolism ; src-Family Kinases/*metabolism ; }, abstract = {Metastasis remains the leading cause of cancer mortality, and reactive oxygen species (ROS) signaling promotes the metastatic cascade. However, the molecular pathways that control ROS signaling relevant to metastasis are little studied. Here, we identify SIRT3, a mitochondrial deacetylase, as a regulator of cell migration via its control of ROS signaling. We find that, although mitochondria are present at the leading edge of migrating cells, SIRT3 expression is down-regulated during migration, resulting in elevated ROS levels. This SIRT3-mediated control of ROS represses Src oxidation and attenuates focal adhesion kinase (FAK) activation. SIRT3 overexpression inhibits migration and metastasis in breast cancer cells. Finally, in human breast cancers, SIRT3 expression is inversely correlated with metastatic outcome and Src/FAK signaling. Our results reveal a role for SIRT3 in cell migration, with important implications for breast cancer progression.}, } @article {pmid29915028, year = {2018}, author = {Harijan, RK and Zoi, I and Antoniou, D and Schwartz, SD and Schramm, VL}, title = {Inverse enzyme isotope effects in human purine nucleoside phosphorylase with heavy asparagine labels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6209-E6216}, pmid = {29915028}, issn = {1091-6490}, support = {P01 GM068036/GM/NIGMS NIH HHS/United States ; R01 GM041916/GM/NIGMS NIH HHS/United States ; R37 GM041916/GM/NIGMS NIH HHS/United States ; }, mesh = {Asparagine/*chemistry/genetics/metabolism ; Catalysis ; Humans ; Isotope Labeling ; Isotopes ; Kinetics ; Purine-Nucleoside Phosphorylase/*chemistry/genetics/metabolism ; }, abstract = {Transition path-sampling calculations with several enzymes have indicated that local catalytic site femtosecond motions are linked to transition state barrier crossing. Experimentally, femtosecond motions can be perturbed by labeling the protein with amino acids containing 13C, 15N, and nonexchangeable 2H. A slowed chemical step at the catalytic site with variable effects on steady-state kinetics is usually observed for heavy enzymes. Heavy human purine nucleoside phosphorylase (PNP) is slowed significantly (kchemlight/kchemheavy = 1.36). An asparagine (Asn243) at the catalytic site is involved in purine leaving-group activation in the PNP catalytic mechanism. In a PNP produced with isotopically heavy asparagines, the chemical step is faster (kchemlight/kchemheavy = 0.78). When all amino acids in PNP are heavy except for the asparagines, the chemical step is also faster (kchemlight/kchemheavy = 0.71). Substrate-trapping experiments provided independent confirmation of improved catalysis in these constructs. Transition path-sampling analysis of these partially labeled PNPs indicate altered femtosecond catalytic site motions with improved Asn243 interactions to the purine leaving group. Altered transition state barrier recrossing has been proposed as an explanation for heavy-PNP isotope effects but is incompatible with these isotope effects. Rate-limiting product release governs steady-state kinetics in this enzyme, and kinetic constants were unaffected in the labeled PNPs. The study suggests that mass-constrained femtosecond motions at the catalytic site of PNP can improve transition state barrier crossing by more frequent sampling of essential catalytic site contacts.}, } @article {pmid29915027, year = {2018}, author = {Gao, Y and Gan, H and Lou, Z and Zhang, Z}, title = {Asf1a resolves bivalent chromatin domains for the induction of lineage-specific genes during mouse embryonic stem cell differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6162-E6171}, pmid = {29915027}, issn = {1091-6490}, mesh = {Animals ; *Cell Differentiation ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; Gene Deletion ; *Gene Expression Regulation ; Histones/genetics/*metabolism ; Mice ; Mouse Embryonic Stem Cells/cytology/*metabolism ; Nucleosomes/genetics/*metabolism ; }, abstract = {Bivalent chromatin domains containing repressive H3K27me3 and active H3K4me3 modifications are barriers for the expression of lineage-specific genes in ES cells and must be resolved for the transcription induction of these genes during differentiation, a process that remains largely unknown. Here, we show that Asf1a, a histone chaperone involved in nucleosome assembly and disassembly, regulates the resolution of bivalent domains and activation of lineage-specific genes during mouse ES cell differentiation. Deletion of Asf1a does not affect the silencing of pluripotent genes, but compromises the expression of lineage-specific genes during ES cell differentiation. Mechanistically, the Asf1a-histone interaction, but not the role of Asf1a in nucleosome assembly, is required for gene transcription. Asf1a is recruited to several bivalent promoters, partially through association with transcription factors, and mediates nucleosome disassembly during differentiation. We suggest that Asf1a-mediated nucleosome disassembly provides a means for resolution of bivalent domain barriers for induction of lineage-specific genes during differentiation.}, } @article {pmid29915026, year = {2018}, author = {Lavergne, FA and Curran, A and Aarts, DGAL and Dullens, RPA}, title = {Dislocation-controlled formation and kinetics of grain boundary loops in two-dimensional crystals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6922-6927}, pmid = {29915026}, issn = {1091-6490}, abstract = {The formation and kinetics of grain boundaries are closely related to the topological constraints imposed on their complex dislocation structure. Loop-shaped grain boundaries are unique structures to establish such a link because their overall topological "charge" is zero due to their null net Burgers vector. Here, we observe that a local rotational deformation of a 2D colloidal crystal with an optical vortex results in a grain boundary loop only if the product of its radius and misorientation exceeds a critical value. Above this value, the deformation is plastic and the grain boundary loop spontaneously shrinks at a rate that solely depends on this product, while otherwise, the deformation is elastically restored. We show that this elastic-to-plastic crossover is a direct consequence of the unique dislocation structure of grain boundary loops. At the critical value, the loop is structurally equivalent to the so-called "flower defect" and the shrinkage rate diverges. Our results thus reveal a general limit on the formation of grain boundary loops in 2D crystals and elucidate the central role of defects in both the onset of plasticity and the kinetics of grain boundaries.}, } @article {pmid29915012, year = {2018}, author = {Barsalou, LW and Dutriaux, L and Scheepers, C}, title = {Moving beyond the distinction between concrete and abstract concepts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915012}, issn = {1471-2970}, abstract = {From the perspective of the situated conceptualization framework, the primary purpose of concepts is for categorizing and integrating elements of situations to support goal-directed action (including communication and social interaction). To the extent that important situational elements are categorized and integrated properly, effective goal-directed action follows. Over time, frequent patterns of co-occurring concepts within situations become established in memory as situated conceptualizations, conditioning the conceptual system and producing habitual patterns of conceptual processing. As a consequence, individual concepts are most basically represented within patterns of concepts that become entrained with specific kinds of physical situations. In this framework, the concrete versus abstract distinction between concepts is no longer useful, with two other distinctions becoming important instead: (i) external versus internal situational elements, (ii) situational elements versus situational integrations. Whereas concepts for situational elements originate in distributed neural networks that provide continual feeds about components of situations, concepts for situational integrations originate in association areas that establish temporal co-occurrence relations between situational elements, both external and internal. We propose that studying concepts in the context of situated action is necessary for establishing complete accounts of them, and that continuing to study concepts in isolation is likely to provide relatively incomplete and distorted accounts.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915011, year = {2018}, author = {Connell, L and Lynott, D and Banks, B}, title = {Interoception: the forgotten modality in perceptual grounding of abstract and concrete concepts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915011}, issn = {1471-2970}, abstract = {Conceptual representations are perceptually grounded, but when investigating which perceptual modalities are involved, researchers have typically restricted their consideration to vision, touch, hearing, taste and smell. However, there is another major modality of perceptual information that is distinct from these traditional five senses; that is, interoception, or sensations inside the body. In this paper, we use megastudy data (modality-specific ratings of perceptual strength for over 32 000 words) to explore how interoceptive information contributes to the perceptual grounding of abstract and concrete concepts. We report how interoceptive strength captures a distinct form of perceptual experience across the abstract-concrete spectrum, but is markedly more important to abstract concepts (e.g. hungry, serenity) than to concrete concepts (e.g. capacity, rainy). In particular, interoception dominates emotion concepts, especially negative emotions relating to fear and sadness, moreso than other concepts of equivalent abstractness and valence. Finally, we examine whether interoceptive strength represents valuable information in conceptual content by investigating its role in concreteness effects in word recognition, and find that it enhances semantic facilitation over and above the traditional five sensory modalities. Overall, these findings suggest that interoception has comparable status to other modalities in contributing to the perceptual grounding of abstract and concrete concepts.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915010, year = {2018}, author = {Fingerhut, J and Prinz, JJ}, title = {Grounding evaluative concepts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915010}, issn = {1471-2970}, abstract = {Evaluative concepts qualify as abstract because they seem to go beyond what is given in experience. This is especially clear in the case of moral concepts. Justice, for example, has no fixed appearance. Less obviously, aesthetic concepts may also qualify as abstract. The very same sensory input can be regarded as beautiful by one person and ugly by another. Artistic success can also transcend sensory accessible features. Here, we focus on moral badness and aesthetic goodness and argue that both can be grounded in emotional responses. Emotions, in turn, are grounded in bodily perceptions, which correspond to action tendencies. When we conceptualize something as good or bad (whether in the moral or aesthetic domain), we experience our bodily responses to that thing. The moral and aesthetic domains are distinguished by the emotions that they involve.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915009, year = {2018}, author = {Brookshire, G and Casasanto, D}, title = {Approach motivation in human cerebral cortex.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915009}, issn = {1471-2970}, abstract = {Different regions of the human cerebral cortex are specialized for different emotions, but the principles underlying this specialization have remained unknown. According to the sword and shield hypothesis, hemispheric specialization for affective motivation, a basic dimension of human emotion, varies across individuals according to the way they use their hands to perform approach- and avoidance-related actions. In a test of this hypothesis, here we measured approach motivation before and after five sessions of transcranial direct current stimulation to increase excitation in the left or right dorsolateral prefrontal cortex, in healthy adults whose handedness ranged from strongly left-handed to strongly right-handed. The strength and direction of participants' handedness predicted whether electrical stimulation to frontal cortex caused an increase or decrease in their experience of approach-related emotions. The organization of approach motivation in the human cerebral cortex varies across individuals as predicted by the organization of the individuals' motor systems. These results show that the large-scale cortical organization of abstract concepts corresponds with the way people use their hands to interact with the world. Affective motivation may re-use neural circuits that evolved for performing approach- and avoidance-related motor actions.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915008, year = {2018}, author = {Ponari, M and Norbury, CF and Rotaru, A and Lenci, A and Vigliocco, G}, title = {Learning abstract words and concepts: insights from developmental language disorder.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915008}, issn = {1471-2970}, abstract = {Some explanations of abstract word learning suggest that these words are learnt primarily from the linguistic input, using statistical co-occurrences of words in language, whereas concrete words can also rely on non-linguistic, experiential information. According to this hypothesis, we expect that, if the learner is not able to fully exploit the information in the linguistic input, abstract words should be affected more than concrete ones. Embodied approaches instead argue that both abstract and concrete words can rely on experiential information and, therefore, there might not be any linguistic primacy. Here, we test the role of linguistic input in the development of abstract knowledge with children with developmental language disorder (DLD) and typically developing children aged 8-13. We show that DLD children, who by definition have impoverished language, do not show a disproportionate impairment for abstract words in lexical decision and definition tasks. These results indicate that linguistic information does not have a primary role in the learning of abstract concepts and words; rather, it would play a significant role in semantic development across all domains of knowledge.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915007, year = {2018}, author = {Majid, A and Burenhult, N and Stensmyr, M and de Valk, J and Hansson, BS}, title = {Olfactory language and abstraction across cultures.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915007}, issn = {1471-2970}, abstract = {Olfaction presents a particularly interesting arena to explore abstraction in language. Like other abstract domains, such as time, odours can be difficult to conceptualize. An odour cannot be seen or held, it can be difficult to locate in space, and for most people odours are difficult to verbalize. On the other hand, odours give rise to primary sensory experiences. Every time we inhale we are using olfaction to make sense of our environment. We present new experimental data from 30 Jahai hunter-gatherers from the Malay Peninsula and 30 matched Dutch participants from the Netherlands in an odour naming experiment. Participants smelled monomolecular odorants and named odours while reaction times, odour descriptors and facial expressions were measured. We show that while Dutch speakers relied on concrete descriptors, i.e. they referred to odour sources (e.g. smells like lemon), the Jahai used abstract vocabulary to name the same odours (e.g. musty). Despite this differential linguistic categorization, analysis of facial expressions showed that the two groups, nevertheless, had the same initial emotional reactions to odours. Critically, these cross-cultural data present a challenge for how to think about abstraction in language.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915006, year = {2018}, author = {Zdrazilova, L and Sidhu, DM and Pexman, PM}, title = {Communicating abstract meaning: concepts revealed in words and gestures.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915006}, issn = {1471-2970}, abstract = {words refer to concepts that cannot be directly experienced through our senses (e.g. truth, morality). How we ground the meanings of abstract words is one of the deepest problems in cognitive science today. We investigated this question in an experiment in which 62 participants were asked to communicate the meanings of words (20 abstract nouns, e.g. impulse; 10 concrete nouns, e.g. insect) to a partner without using the words themselves (the taboo task). We analysed the speech and associated gestures that participants used to communicate the meaning of each word in the taboo task. Analysis of verbal and gestural data yielded a number of insights. When communicating about the meanings of abstract words, participants' speech referenced more people and introspections. In contrast, the meanings of concrete words were communicated by referencing more objects and entities. Gesture results showed that when participants spoke about abstract word meanings their speech was accompanied by more metaphorical and beat gestures, and speech about concrete word meanings was accompanied by more iconic gestures. Taken together, the results suggest that abstract meanings are best captured by a model that allows dynamic access to multiple representation systems.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915005, year = {2018}, author = {Lupyan, G and Winter, B}, title = {Language is more abstract than you think, or, why aren't languages more iconic?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915005}, issn = {1471-2970}, abstract = {How abstract is language? We show that abstractness pervades every corner of language, going far beyond the usual examples of freedom and justice In the light of the ubiquity of abstract words, the need to understand where abstract meanings come from becomes ever more acute. We argue that the best source of knowledge about abstract meanings may be language itself. We then consider a seemingly unrelated question: Why isn't language more iconic? Iconicity-a resemblance between the form of words and their meanings-can be immensely useful in language learning and communication. Languages could be much more iconic than they currently are. So why aren't they? We suggest that one reason is that iconicity is inimical to abstraction because iconic forms are too connected to specific contexts and sensory depictions. Form-meaning arbitrariness may allow language to better convey abstract meanings.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915004, year = {2018}, author = {Rice, GE and Hoffman, P and Binney, RJ and Lambon Ralph, MA}, title = {Concrete versus abstract forms of social concept: an fMRI comparison of knowledge about people versus social terms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915004}, issn = {1471-2970}, support = {MR/J004146/1//Medical Research Council/United Kingdom ; }, abstract = {The anterior temporal lobes (ATLs) play a key role in conceptual knowledge representation. The hub-and-spoke theory suggests that the contribution of the ATLs to semantic representation is (a) transmodal, i.e. integrating information from multiple sensorimotor and verbal modalities, and (b) pan-categorical, representing concepts from all categories. Another literature, however, suggests that this region's responses are modality- and category-selective; prominent examples include category selectivity for socially relevant concepts and face recognition. The predictions of each approach have never been directly compared. We used data from three studies to compare category-selective responses within the ATLs. Study 1 compared ATL responses to famous people versus another conceptual category (landmarks) from visual versus auditory inputs. Study 2 compared ATL responses to famous people from pictorial and written word inputs. Study 3 compared ATL responses to a different kind of socially relevant stimuli, namely abstract non-person-related words, in order to ascertain whether ATL subregions are engaged for social concepts more generally or only for person-related knowledge. Across all three studies a dominant bilateral ventral ATL cluster responded to all categories in all modalities. Anterior to this 'pan-category' transmodal region, a second cluster responded more weakly overall yet selectively for people, but did so equally for spoken names and faces (Study 1). A third region in the anterior superior temporal gyrus responded selectively to abstract socially relevant words (Study 3), but did not respond to concrete socially relevant words (i.e. written names; Study 2). These findings can be accommodated by the graded hub-and-spoke model of concept representation. On this view, the ventral ATL is the centre point of a bilateral ATL hub, which contributes to conceptual representation through transmodal distillation of information arising from multiple modality-specific association cortices. Partial specialization occurs across the graded ATL hub as a consequence of gradedly differential connectivity across the region.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915003, year = {2018}, author = {Dove, G}, title = {Language as a disruptive technology: abstract concepts, embodiment and the flexible mind.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915003}, issn = {1471-2970}, abstract = {A growing body of evidence suggests that cognition is embodied and grounded. Abstract concepts, though, remain a significant theoretical challenge. A number of researchers have proposed that language makes an important contribution to our capacity to acquire and employ concepts, particularly abstract ones. In this essay, I critically examine this suggestion and ultimately defend a version of it. I argue that a successful account of how language augments cognition should emphasize its symbolic properties and incorporate a view of embodiment that recognizes the flexible, multimodal and task-related nature of action, emotion and perception systems. On this view, language is an ontogenetically disruptive cognitive technology that expands our conceptual reach.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915002, year = {2018}, author = {Borghi, AM and Barca, L and Binkofski, F and Tummolini, L}, title = {Abstract concepts, language and sociality: from acquisition to inner speech.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915002}, issn = {1471-2970}, abstract = {The problem of representation of abstract concepts, such as 'freedom' and 'justice', has become particularly crucial in recent years, owing to the increased success of embodied and grounded views of cognition. We will present a novel view on abstract concepts and abstract words. Since abstract concepts do not have single objects as referents, children and adults might rely more on input from others to learn them; we, therefore, suggest that linguistic and social experience play an important role for abstract concepts. We will discuss evidence obtained in our and other laboratories showing that processing of abstract concepts evokes linguistic interaction and social experiences, leading to the activation of the mouth motor system. We will discuss the possible mechanisms that underlie this activation. Mouth motor system activation can be due to re-enactment of the experience of conceptual acquisition, which occurred through the mediation of language. Alternatively, it could be due to the re-explanation of the word meaning, possibly through inner speech. Finally, it can be due to a metacognitive process revealing low confidence in the meaning of our concepts. This process induces in us the need to rely on others to ask/negotiate conceptual meaning. We conclude that with abstract concepts language works as a social tool: it extends our thinking abilities and pushes us to rely on others to integrate our knowledge.This article is part of the theme issue 'Varieties of abstract concepts: development, use, and representation in the brain'.}, } @article {pmid29915001, year = {2018}, author = {Shea, N}, title = {Metacognition and abstract concepts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915001}, issn = {1471-2970}, abstract = {The problem of how concepts can refer to or be about the non-mental world is particularly puzzling for abstract concepts. There is growing evidence that many characteristics beyond the perceptual are involved in grounding different kinds of abstract concept. A resource that has been suggested, but little explored, is introspection. This paper develops that suggestion by focusing specifically on metacognition-on the thoughts and feelings that thinkers have about a concept. One example of metacognition about concepts is the judgement that we should defer to others in how a given concept is used. Another example is our internal assessment of which concepts are dependable and useful, and which less so. Metacognition of this kind may be especially important for grounding abstract concepts.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29915000, year = {2018}, author = {Pecher, D and Zeelenberg, R}, title = {Boundaries to grounding abstract concepts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29915000}, issn = {1471-2970}, abstract = {Grounded theories of cognition claim that concept representation relies on the systems for perception and action. The sensory-motor grounding of abstract concepts presents a challenge for these theories. Some accounts propose that abstract concepts are indirectly grounded via image schemas or situations. Recent research, however, indicates that the role of sensory-motor processing for concrete concepts may be limited, providing evidence against the idea that abstract concepts are grounded via concrete concepts. Hybrid models that combine language and sensory-motor experience may provide a more viable account of abstract and concrete representations. We propose that sensory-motor grounding is important during acquisition and provides structure to concepts. Later activation of concepts relies on this structure but does not necessarily involve sensory-motor processing. Language is needed to create coherent concepts from diverse sensory-motor experiences.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914999, year = {2018}, author = {Cangelosi, A and Stramandinoli, F}, title = {A review of abstract concept learning in embodied agents and robots.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914999}, issn = {1471-2970}, abstract = {This paper reviews computational modelling approaches to the learning of abstract concepts and words in embodied agents such as humanoid robots. This will include a discussion of the learning of abstract words such as 'use' and 'make' in humanoid robot experiments, and the acquisition of numerical concepts via gesture and finger counting strategies. The current approaches share a strong emphasis on embodied cognition aspects for the grounding of abstract concepts, and a continuum, rather than dichotomy, view of concrete/abstract concepts differences.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914998, year = {2018}, author = {Román, A and Flumini, A and Santiago, J}, title = {Scanning of speechless comics changes spatial biases in mental model construction.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914998}, issn = {1471-2970}, abstract = {The mental representation of both time and number shows lateral spatial biases, which can be affected by habitual reading and writing direction. However, this effect is in place before children begin to read. One potential early cause is the experiences of looking at picture books together with a carer, as those images also follow the directionality of the script. What is the underlying mechanism for this effect? In the present study, we test the possibility that such experiences induce spatial biases in mental model construction, a mechanism which is a good candidate to induce the biases observed with numbers and times. We presented a speechless comic in either standard (left-to-right) or mirror-reversed (right-to-left) form to adult Spanish participants. We then asked them to draw the scene depicted by sentences like 'the square is between the cross and the circle'. The position of the lateral objects in these drawings reveals the spatial biases at work when building mental models in working memory. Under conditions of highly consistent directionality, the mirror comic changed pre-existing lateral biases. Processes of mental model construction in working memory stand as a potential mechanism for the generation of spatial biases for time and number.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914997, year = {2018}, author = {Pulvermüller, F}, title = {The case of CAUSE: neurobiological mechanisms for grounding an abstract concept.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914997}, issn = {1471-2970}, abstract = {How can we understand causal relationships and how can we understand words such as 'cause'? Some theorists assume that the underlying abstract concept is given to us, and that perceptual correlation provides the relevant hints towards inferring causation from perceived real-life events. A different approach emphasizes the role of actions and their typical consequences for the emergence of the concept of causation and the application of the related term. A model of causation is proposed that highlights the family resemblance between causal actions and postulates that symbols are necessary for binding together the different partially shared semantic features of subsets of causal actions and their goals. Linguistic symbols are proposed to play a key role in binding the different subsets of semantic features of the abstract concept. The model is spelt out at the neuromechanistic level of distributed cortical circuits and the cognitive functions they carry. The model is discussed in light of behavioural and neuroscience evidence, and questions for future research are highlighted. In sum, taking causation as a concrete example, I argue that abstract concepts and words can be learnt and grounded in real-life interaction, and that the neurobiological mechanisms realizing such abstract semantic grounding are within our grasp.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914996, year = {2018}, author = {Cuccio, V and Gallese, V}, title = {A Peircean account of concepts: grounding abstraction in phylogeny through a comparative neuroscientific perspective.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914996}, issn = {1471-2970}, abstract = {The nature of concepts has always been a hotly debated topic in both philosophy and psychology and, more recently, also in cognitive neuroscience. Different accounts have been proposed of what concepts are. These accounts reflect deeply different conceptions of how the human mind works. In the last decades, two diametrically opposed theories of human cognition have been discussed and empirically investigated: the Computational Theory of Mind, on the one hand (Fodor 1983 The modularity of mind: an essay on faculty psychology; Pylyshyn 1984 Computation and cognition: toward a foundation for cognitive science), and Embodied Cognition (Barsalou 2008 Annu. Rev. Psychol.59, 617-645. (doi:10.1146/annurev.psych.59.103006.093639); Gallese & Lakoff 2005 Cogn. Neuropsychol.22, 455-479 (doi:10.1080/02643290442000310); Shapiro 2011 Embodied cognition), on the other hand. The former proposes that concepts are abstract and amodal symbols in the language of thought, while the latter argues for the embodied nature of concepts that are conceived of as grounded in actions and perception. The embodiment of both concrete and abstract concepts has been challenged by many (e.g. Mahon & Caramazza 2008 J. Physiol.102, 59-70. (doi:10.1016/j.jphysparis.2008.03.004); Caramazza et al 2014 Annu. Rev. Neurosci.37, 1-15. (doi:10.1146/annurev-neuro-071013-013950)). These challenges will be here taken seriously and addressed from a comparative perspective. We will provide a phylogenetic and neurobiologically inspired account of the embodied nature of both abstract and concrete concepts. We will propose that, although differing in certain respect, they both might have a bodily foundation. Commonalities between abstract and concrete concepts will be explained by recurring to the Peircean notions of icon and abductive inference (CP 2.247). According to Peirce, icons are the kind of signs on which abductive inferences rest (Peirce CS 1931 in Collected papers of Charles S. Peirce, Hartshorne C, Weiss P, Burks AW. (eds), 40; Peirce CS 1997 In The 1903 Harvard lectures on pragmatism (ed. A. Turrisi)). It will be claimed that the mechanism of Embodied Simulation (Gallese & Sinigaglia 2011 Trends Cogn. Sci.15, 512-519. (doi:10.1016/j.tics.2011.09.003)) can be described as an icon (Cuccio V & Caruana F. 2015 Il corpo come icona. Abduzione, strumenti ed Embodied Simulation. Versus, n. 119, 93-103), and it will then be suggested that on these, basic natural signs rest, both phylogenetically and ontogenetically, the capacity to conceptualize.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914995, year = {2018}, author = {Winkielman, P and Coulson, S and Niedenthal, P}, title = {Dynamic grounding of emotion concepts.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914995}, issn = {1471-2970}, abstract = {Emotion concepts are important. They help us to understand, experience and predict human behaviour. Emotion concepts also link the realm of the abstract with the realm of bodily experience and actions. Accordingly, the key question is how such concepts are created, represented and used. Embodied cognition theories hold that concepts are grounded in neural systems that produce experiential and motor states. Concepts are also contextually situated and thus engage sensorimotor resources in a dynamic, flexible way. Finally, on that framework, conceptual understanding unfolds in time, reflecting embodied as well as linguistic and cultural influences. In this article, we review empirical work on emotion concepts and show how it highlights their grounded, yet dynamic and context-sensitive nature. The conclusions are consistent with recent developments in embodied cognition that allow concepts to be linked to sensorimotor systems, yet be flexibly sensitive to current representational and action needs.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914994, year = {2018}, author = {Semin, GR and Palma, T and Acartürk, C and Dziuba, A}, title = {Gender is not simply a matter of black and white, or is it?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914994}, issn = {1471-2970}, abstract = {Based on research in physical anthropology, we argue that brightness marks the abstract category of gender, with light colours marking the female gender and dark colours marking the male gender. In a set of three experiments, we examine this hypothesis, first in a speeded gender classification experiment with male and female names presented in black and white. As expected, male names in black and female names in white are classified faster than the reverse gender-colour combinations. The second experiment relies on a gender classification task involving the disambiguation of very briefly appearing non-descript stimuli in the form of black and white 'blobs'. The former are classified predominantly as male and the latter as female names. Finally, the processes driving light and dark object choices for males and females are examined by tracking the number of fixations and their duration in an eye-tracking experiment. The results reveal that when choosing for a male target, participants look longer and make more fixations on dark objects, and the same for light objects when choosing for a female target. The implications of these findings, which repeatedly reveal the same data patterns across experiments with Dutch, Portuguese and Turkish samples for the abstract category of gender, are discussed. The discussion attempts to enlarge the subject beyond mainstream models of embodied grounding.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914993, year = {2018}, author = {Fischer, MH and Shaki, S}, title = {Number concepts: abstract and embodied.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914993}, issn = {1471-2970}, abstract = {Numerical knowledge, including number concepts and arithmetic procedures, seems to be a clear-cut case for abstract symbol manipulation. Yet, evidence from perceptual and motor behaviour reveals that natural number knowledge and simple arithmetic also remain closely associated with modal experiences. Following a review of behavioural, animal and neuroscience studies of number processing, we propose a revised understanding of psychological number concepts as grounded in physical constraints, embodied in experience and situated through task-specific intentions. The idea that number concepts occupy a range of positions on the continuum between abstract and modal conceptual knowledge also accounts for systematic heuristics and biases in mental arithmetic, thus inviting psycho-logical approaches to the study of the mathematical mind.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914992, year = {2018}, author = {Ghio, M and Haegert, K and Vaghi, MM and Tettamanti, M}, title = {Sentential negation of abstract and concrete conceptual categories: a brain decoding multivariate pattern analysis study.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914992}, issn = {1471-2970}, abstract = {We rarely use abstract and concrete concepts in isolation but rather embedded within a linguistic context. To examine the modulatory impact of the linguistic context on conceptual processing, we isolated the case of sentential negation polarity, in which an interaction occurs between the syntactic operator not and conceptual information in the negation's scope. Previous studies suggested that sentential negation of concrete action-related concepts modulates activation in the fronto-parieto-temporal action representation network. In this functional magnetic resonance imaging study, we examined the influence of negation on a wider spectrum of meanings, by factorially manipulating sentence polarity (affirmative, negative) and fine-grained abstract (mental state, emotion, mathematics) and concrete (related to mouth, hand, leg actions) conceptual categories. We adopted a multivariate pattern analysis approach, and tested the accuracy of a machine learning classifier in discriminating brain activation patterns associated to the factorial manipulation. Searchlight analysis was used to localize the discriminating patterns. Overall, the neural processing of affirmative and negative sentences with either an abstract or concrete content could be accurately predicted by means of multivariate classification. We suggest that sentential negation polarity modulates brain activation in distributed representational semantic networks, through the functional mediation of syntactic and cognitive control systems.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914991, year = {2018}, author = {Desai, RH and Reilly, M and van Dam, W}, title = {The multifaceted abstract brain.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914991}, issn = {1471-2970}, abstract = {concepts play a central role in human behaviour and constitute a critical component of the human conceptual system. Here, we investigate the neural basis of four types of abstract concepts, examining their similarities and differences through neuroimaging meta-analyses. We examine numerical and emotional concepts, and two higher-order abstract processes, morality judgements and theory of mind. Three main findings emerge. First, representation of abstract concepts is more widespread than is often assumed. Second, representations of different types of abstract concepts differ in important respects. Each of the domains examined here was associated with some unique areas. Third, some areas were commonly activated across domains and included inferior parietal, posterior cingulate and medial prefrontal cortex. We interpret these regions in terms of their role in episodic recall, event representation and social-emotional processing. We suggest that different types of abstract concepts can be represented and grounded through differing contributions from event-based, interoceptive, introspective and sensory-motor representations. The results underscore the richness and diversity of abstract concepts, argue against single-mechanism accounts for representation of all types of abstract concepts and suggest mechanisms for their direct and indirect grounding.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914990, year = {2018}, author = {Borghi, AM and Barca, L and Binkofski, F and Tummolini, L}, title = {Varieties of abstract concepts: development, use and representation in the brain.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1752}, pages = {}, pmid = {29914990}, issn = {1471-2970}, abstract = {The capacity for abstract thought is one of the hallmarks of human cognition. However, the mechanisms underlying the ability to form and use abstract concepts like 'fantasy' and 'grace' have not been elucidated yet. This theme issue brings together developmental, social and cognitive psychologists, linguists, anthropologists, cognitive scientists, neuroscientists, philosophers and computer scientists to present theoretical insights and novel evidence on how abstract concepts are acquired, used and represented in the brain. Many of the contributions conceive concepts as grounded in sensorimotor systems and constrained by bodily mechanisms and structures. The theme issue develops along two main axes, related to the most promising research directions on abstract concepts. The axes focus on (i) the different kinds of abstract concepts (numbers, emotions, evaluative concepts like moral and aesthetic ones, social concepts); (ii) the role played by perception and action, language and sociality, and inner processes (emotions, interoception, metacognition) in grounding abstract concepts. Most papers adopt a cognitive science/neuroscience approach, but the theme issue also includes studies on development, on social cognition, and on how linguistic diversity shapes abstract concepts. Overall, the theme issue provides an integrated theoretical account that highlights the importance of language, sociality and inner processes for abstract concepts, and that offers new methodological tools to investigate them.This article is part of the theme issue 'Varieties of abstract concepts: development, use and representation in the brain'.}, } @article {pmid29914555, year = {2018}, author = {Anderson, KE and Ricigliano, VA and Mott, BM and Copeland, DC and Floyd, AS and Maes, P}, title = {The queen's gut refines with age: longevity phenotypes in a social insect model.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {108}, pmid = {29914555}, issn = {2049-2618}, mesh = {Animals ; Base Sequence ; Bees ; Bifidobacterium/classification/genetics/*isolation & purification ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Lactobacillus/classification/genetics/*isolation & purification ; Longevity/*physiology ; Oxidative Stress/genetics ; Proteobacteria/classification/genetics/*isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: In social insects, identical genotypes can show extreme lifespan variation providing a unique perspective on age-associated microbial succession. In honey bees, short- and long-lived host phenotypes are polarized by a suite of age-associated factors including hormones, nutrition, immune senescence, and oxidative stress. Similar to other model organisms, the aging gut microbiota of short-lived (worker) honey bees accrue Proteobacteria and are depleted of Lactobacillus and Bifidobacterium, consistent with a suite of host senescence markers. In contrast, long-lived (queen) honey bees maintain youthful cellular function with much lower expression of oxidative stress genes, suggesting a very different host environment for age-associated microbial succession.

RESULTS: We sequenced the microbiota of 63 honey bee queens exploring two chronological ages and four alimentary tract niches. To control for genetic and environmental variation, we quantified carbonyl accumulation in queen fat body tissue as a proxy for biological aging. We compared our results to the age-specific microbial succession of worker guts. Accounting for queen source variation, two or more bacterial species per niche differed significantly by queen age. Biological aging in queens was correlated with microbiota composition highlighting the relationship of microbiota with oxidative stress. Queens and workers shared many major gut bacterial species, but differ markedly in community structure and age succession. In stark contrast to aging workers, carbonyl accumulation in queens was significantly associated with increased Lactobacillus and Bifidobacterium and depletion of various Proteobacteria.

CONCLUSIONS: We present a model system linking changes in gut microbiota to diet and longevity, two of the most confounding variables in human microbiota research. The pattern of age-associated succession in the queen microbiota is largely the reverse of that demonstrated for workers. The guts of short-lived worker phenotypes are progressively dominated by three major Proteobacteria, but these same species were sparse or significantly depleted in long-lived queen phenotypes. More broadly, age-related changes in the honey bee microbiota reflect the regulatory anatomy of reproductive host metabolism. Our synthesis suggests that the evolution of colony-level reproductive physiology formed the context for host-microbial interactions and age-related succession of honey bee microbiota.}, } @article {pmid29914549, year = {2018}, author = {Gao, B and Nzekwu, E and Cook, AJ and Spaner, SJ}, title = {Case report: Diffuse hyperplastic perilobar nephroblastomatosis complicated by a unilateral Wilms tumour: diagnosis, treatment and follow-up.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {396}, pmid = {29914549}, issn = {1756-0500}, mesh = {Female ; Humans ; Infant ; Kidney Neoplasms/*diagnosis/diagnostic imaging/*surgery ; Nephrectomy ; Wilms Tumor/*diagnosis/diagnostic imaging/*surgery ; }, abstract = {BACKGROUND: Nephroblastomatosis is an uncommon pathologic process characterized by the presence of persistent embryonic nephrogenic rests. Progression to Wilms tumour occurs in an estimated 35% of patients. Cure rates are based on histologic findings and disease stage and have improved from 10% in the 1920s to over 90% today.

CASE PRESENTATION: We report a case of a 9-month-old female presenting with a 2-month history of abdominal distension. Ultrasonographic and computed tomographic assessments demonstrated features consistent with bilateral, diffuse, hyperplastic perilobar nephroblastomatosis (DHPLNB) for which she underwent chemotherapy. Magnetic resonance imaging 6 weeks following commencement of chemotherapy revealed a mass concerning for unilateral Wilms tumor for which she underwent partial nephrectomy. Pathology confirmed DHPLNB with a unilateral Wilms tumor.

CONCLUSION: 3.5 year radiographic follow up demonstrates complete recovery. To our knowledge, there are no similar cases with imaging depiction recently published. With potential for malignant transformation into Wilms tumour and low survival rate for late diagnosed Wilms tumors, it is important to recognize nephroblastomatosis early, both clinically and radiographically to improve overall patient prognosis.}, } @article {pmid29914483, year = {2018}, author = {Folch-Fortuny, A and Teusink, B and Hoefsloot, HCJ and Smilde, AK and Ferrer, A}, title = {Dynamic elementary mode modelling of non-steady state flux data.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {71}, pmid = {29914483}, issn = {1752-0509}, support = {DPI2014-55276-C5-1R//Ministerio de Economía y Competitividad/ ; }, abstract = {BACKGROUND: A novel framework is proposed to analyse metabolic fluxes in non-steady state conditions, based on the new concept of dynamic elementary mode (dynEM): an elementary mode activated partially depending on the time point of the experiment.

RESULTS: Two methods are introduced here: dynamic elementary mode analysis (dynEMA) and dynamic elementary mode regression discriminant analysis (dynEMR-DA). The former is an extension of the recently proposed principal elementary mode analysis (PEMA) method from steady state to non-steady state scenarios. The latter is a discriminant model that permits to identify which dynEMs behave strongly different depending on the experimental conditions. Two case studies of Saccharomyces cerevisiae, with fluxes derived from simulated and real concentration data sets, are presented to highlight the benefits of this dynamic modelling.

CONCLUSIONS: This methodology permits to analyse metabolic fluxes at early stages with the aim of i) creating reduced dynamic models of flux data, ii) combining many experiments in a single biologically meaningful model, and iii) identifying the metabolic pathways that drive the organism from one state to another when changing the environmental conditions.}, } @article {pmid29914482, year = {2018}, author = {Huang, B and Jia, D and Feng, J and Levine, H and Onuchic, JN and Lu, M}, title = {RACIPE: a computational tool for modeling gene regulatory circuits using randomization.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {74}, pmid = {29914482}, issn = {1752-0509}, support = {R1111//the Cancer Prevention and Research Institute of Texas (CPRIT)/ ; PHY-1605817//National Science Foundation/ ; DMS-1361411//National Science Foundation/ ; R1110//the Cancer Prevention and Research Institute of Texas (CPRIT)/ ; P30 CA034196/CA/NCI NIH HHS/United States ; P30CA034196//National Cancer Institute/ ; PHY-1427654//National Science Foundation/ ; }, abstract = {BACKGROUND: One of the major challenges in traditional mathematical modeling of gene regulatory circuits is the insufficient knowledge of kinetic parameters. These parameters are often inferred from existing experimental data and/or educated guesses, which can be time-consuming and error-prone, especially for large networks.

RESULTS: We present a user-friendly computational tool for the community to use our newly developed method named random circuit perturbation (RACIPE), to explore the robust dynamical features of gene regulatory circuits without the requirement of detailed kinetic parameters. Taking the network topology as the only input, RACIPE generates an ensemble of circuit models with distinct randomized parameters and uniquely identifies robust dynamical properties by statistical analysis. Here, we discuss the implementation of the software and the statistical analysis methods of RACIPE-generated data to identify robust gene expression patterns and the functions of genes and regulatory links. Finally, we apply the tool on coupled toggle-switch circuits and a published circuit of B-lymphopoiesis.

CONCLUSIONS: We expect our new computational tool to contribute to a more comprehensive and unbiased understanding of mechanisms underlying gene regulatory networks. RACIPE is a free open source software distributed under (Apache 2.0) license and can be downloaded from GitHub (https://github.com/simonhb1990/RACIPE-1.0).}, } @article {pmid29914480, year = {2018}, author = {Hernansaiz-Ballesteros, RD and Cardelli, L and Csikász-Nagy, A}, title = {Single molecules can operate as primitive biological sensors, switches and oscillators.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {70}, pmid = {29914480}, issn = {1752-0509}, support = {EFOP-3.6.2-16-2017-00013//European Social Fund/ ; Royal Society Research Professorship RP120138//Royal Society/ ; }, abstract = {BACKGROUND: Switch-like and oscillatory dynamical systems are widely observed in biology. We investigate the simplest biological switch that is composed of a single molecule that can be autocatalytically converted between two opposing activity forms. We test how this simple network can keep its switching behaviour under perturbations in the system.

RESULTS: We show that this molecule can work as a robust bistable system, even for alterations in the reactions that drive the switching between various conformations. We propose that this single molecule system could work as a primitive biological sensor and show by steady state analysis of a mathematical model of the system that it could switch between possible states for changes in environmental signals. Particularly, we show that a single molecule phosphorylation-dephosphorylation switch could work as a nucleotide or energy sensor. We also notice that a given set of reductions in the reaction network can lead to the emergence of oscillatory behaviour.

CONCLUSIONS: We propose that evolution could have converted this switch into a single molecule oscillator, which could have been used as a primitive timekeeper. We discuss how the structure of the simplest known circadian clock regulatory system, found in cyanobacteria, resembles the proposed single molecule oscillator. Besides, we speculate if such minimal systems could have existed in an RNA world.}, } @article {pmid29914475, year = {2018}, author = {Smith, RW and van Rosmalen, RP and Martins Dos Santos, VAP and Fleck, C}, title = {DMPy: a Python package for automated mathematical model construction of large-scale metabolic systems.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {72}, pmid = {29914475}, issn = {1752-0509}, support = {316723//FP7 Marie Curie Initial Training Network/ ; 316723//FP7 Marie Curie Initial Training Network/ ; RGP0025/2013//Human Frontier Science Program (FR)/ ; 635536//Horizon 2020/ ; 634942//Horizon 2020/ ; 634942//Horizon 2020/ ; }, abstract = {BACKGROUND: Models of metabolism are often used in biotechnology and pharmaceutical research to identify drug targets or increase the direct production of valuable compounds. Due to the complexity of large metabolic systems, a number of conclusions have been drawn using mathematical methods with simplifying assumptions. For example, constraint-based models describe changes of internal concentrations that occur much quicker than alterations in cell physiology. Thus, metabolite concentrations and reaction fluxes are fixed to constant values. This greatly reduces the mathematical complexity, while providing a reasonably good description of the system in steady state. However, without a large number of constraints, many different flux sets can describe the optimal model and we obtain no information on how metabolite levels dynamically change. Thus, to accurately determine what is taking place within the cell, finer quality data and more detailed models need to be constructed.

RESULTS: In this paper we present a computational framework, DMPy, that uses a network scheme as input to automatically search for kinetic rates and produce a mathematical model that describes temporal changes of metabolite fluxes. The parameter search utilises several online databases to find measured reaction parameters. From this, we take advantage of previous modelling efforts, such as Parameter Balancing, to produce an initial mathematical model of a metabolic pathway. We analyse the effect of parameter uncertainty on model dynamics and test how recent flux-based model reduction techniques alter system properties. To our knowledge this is the first time such analysis has been performed on large models of metabolism. Our results highlight that good estimates of at least 80% of the reaction rates are required to accurately model metabolic systems. Furthermore, reducing the size of the model by grouping reactions together based on fluxes alters the resulting system dynamics.

CONCLUSION: The presented pipeline automates the modelling process for large metabolic networks. From this, users can simulate their pathway of interest and obtain a better understanding of how altering conditions influences cellular dynamics. By testing the effects of different parameterisations we are also able to provide suggestions to help construct more accurate models of complete metabolic systems in the future.}, } @article {pmid29914471, year = {2018}, author = {Karp, PD and Weaver, D and Latendresse, M}, title = {How accurate is automated gap filling of metabolic models?.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {73}, pmid = {29914471}, issn = {1752-0509}, support = {R01 GM075742/GM/NIGMS NIH HHS/United States ; GM075742//National Institute of General Medical Sciences/ ; }, abstract = {BACKGROUND: Reaction gap filling is a computational technique for proposing the addition of reactions to genome-scale metabolic models to permit those models to run correctly. Gap filling completes what are otherwise incomplete models that lack fully connected metabolic networks. The models are incomplete because they are derived from annotated genomes in which not all enzymes have been identified. Here we compare the results of applying an automated likelihood-based gap filler within the Pathway Tools software with the results of manually gap filling the same metabolic model. Both gap-filling exercises were applied to the same genome-derived qualitative metabolic reconstruction for Bifidobacterium longum subsp. longum JCM 1217, and to the same modeling conditions - anaerobic growth under four nutrients producing 53 biomass metabolites.

RESULTS: The solution computed by the gap-filling program GenDev contained 12 reactions, but closer examination showed that solution was not minimal; two of the twelve reactions can be removed to yield a set of ten reactions that enable model growth. The manually curated solution contained 13 reactions, eight of which were shared with the 12-reaction computed solution. Thus, GenDev achieved recall of 61.5% and precision of 66.6%. These results suggest that although computational gap fillers are populating metabolic models with significant numbers of correct reactions, automatically gap-filled metabolic models also contain significant numbers of incorrect reactions.

CONCLUSIONS: Our conclusion is that manual curation of gap-filler results is needed to obtain high-accuracy models. Many of the differences between the manual and automatic solutions resulted from using expert biological knowledge to direct the choice of reactions within the curated solution, such as reactions specific to the anaerobic lifestyle of B. longum.}, } @article {pmid29914391, year = {2018}, author = {El-Hawaz, RF and Grace, MH and Janbey, A and Lila, MA and Adelberg, JW}, title = {In vitro mineral nutrition of Curcuma longa L. affects production of volatile compounds in rhizomes after transfer to the greenhouse.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {122}, pmid = {29914391}, issn = {1471-2229}, mesh = {Bioreactors ; Calcium/metabolism ; Curcuma/drug effects/*metabolism ; *Fertilizers ; Gas Chromatography-Mass Spectrometry ; In Vitro Techniques ; Magnesium/metabolism ; Minerals/*pharmacology ; Nitrates/metabolism ; Phosphates/metabolism ; Potassium Compounds/metabolism ; Rhizome/drug effects/*metabolism ; Volatile Organic Compounds/*metabolism ; }, abstract = {BACKGROUND: Turmeric is a rich source of bioactive compounds useful in both medicine and cuisine. Mineral concentrations effects (PO43-, Ca2+, Mg2+, and KNO3) were tested during in vitro rhizome development on the ex vitro content of volatile constituents in rhizomes after 6 months in the greenhouse. A response surface method (D-optimal criteria) was repeated in both high and low-input fertilizer treatments. Control plants were grown on Murashige and Skoog (MS) medium, acclimatized in the greenhouse and grown in the field. The volatile constituents were investigated by GC-MS.

RESULTS: The total content of volatiles was affected by fertilizer treatments, and in vitro treatment with Ca2+ and KNO3; but PO43- and Mg2+ had no significant effect. The content was higher in the high-input fertilizer treatments (49.7 ± 9 mg/g DM) with 4 mM Ca2+, 60 mM KNO3 and 5 mM NH4+, than the low-input fertilizer (26.6 ± 9 mg/g DM), and the MS control (15.28 ± 2.7 mg/g DM; 3 mM Ca2+, 20 mM K+, 39 mM NO3-, 20 mM NH4+, 1.25 mM PO43-, and 1.5 mM Mg2+). The interaction of Ca2+ with KNO3 affected curcumenol isomer I and II, germacrone, isocurcumenol, and β-elemenone content. Increasing in vitro phosphate concentration to 6.25 mM increased ex vitro neocurdione and methenolone contents.

CONCLUSION: These results show that minerals in the in vitro bioreactor medium during rhizome development affected biosynthesis of turmeric volatile components after transfer to the greenhouse six months later. The multi-factor design identified 1) nutrient regulation of specific components within unique phytochemical profile for Curcuma longa L. clone 35-1 and 2) the varied phytochemical profiles were maintained with integrity during the greenhouse growth in high fertility conditions.}, } @article {pmid29914379, year = {2018}, author = {Singh, DK and Lee, HK and Dweikat, I and Mysore, KS}, title = {An efficient and improved method for virus-induced gene silencing in sorghum.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {123}, pmid = {29914379}, issn = {1471-2229}, mesh = {*Bromovirus/genetics ; DNA, Antisense/genetics ; Flowers/virology ; *Gene Silencing ; Plant Leaves/virology ; Sorghum/*genetics/metabolism/virology ; Temperature ; Ubiquitin/metabolism ; }, abstract = {BACKGROUND: Although the draft genome of sorghum is available, the understanding of gene function is limited due to the lack of extensive mutant resources. Virus-induced gene silencing (VIGS) is an alternative to mutant resources to study gene function. This study reports an improved and efficient method for Brome mosaic virus (BMV)-based VIGS in sorghum.

METHODS: Sorghum plants were rub-inoculated with sap prepared by grinding 2 g of infected Nicotiana benthamiana leaf in 1 ml 10 mM potassium phosphate buffer (pH 6.8) and 100 mg of carborundum abrasive. The sap was rubbed on two to three top leaves of sorghum. Inoculated plants were covered with a dome to maintain high humidity and kept in the dark for two days at 18 °C. Inoculated plants were then transferred to 18 °C growth chamber with 12 h/12 h light/dark cycle.

RESULTS: This study shows that BMV infection rate can be significantly increased in sorghum by incubating plants at 18 °C. A substantial variation in BMV infection rate in sorghum genotypes/varieties was observed and BTx623 was the most susceptible. Ubiquitin (Ubiq) silencing is a better visual marker for VIGS in sorghum compared to other markers such as Magnesium Chelatase subunit H (ChlH) and Phytoene desaturase (PDS). The use of antisense strand of a gene in BMV was found to significantly increase the efficiency and extent of VIGS in sorghum. In situ hybridization experiments showed that the non-uniform silencing in sorghum is due to the uneven spread of the virus. This study further demonstrates that genes could also be silenced in the inflorescence of sorghum.

CONCLUSION: In general, sorghum plants are difficult to infect with BMV and therefore recalcitrant to VIGS studies. However, by using BMV as a vector, a BMV susceptible sorghum variety, 18 °C for incubating plants, and antisense strand of the target gene fragment, efficient VIGS can still be achieved in sorghum.}, } @article {pmid29914378, year = {2018}, author = {Xue, XF and Deng, W and Qu, SX and Hong, XY and Shao, R}, title = {The mitochondrial genomes of sarcoptiform mites: are any transfer RNA genes really lost?.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {466}, pmid = {29914378}, issn = {1471-2164}, support = {31672337//the National Natural Science Foundation of China/ ; KYZ201405//the Fundamental Research Funds for the Central Universities/ ; DP120100240//the Australian Research Council/ ; ACSRF00980//Australia-China Science & Research Fund/ ; }, mesh = {Animals ; Base Sequence ; DNA, Mitochondrial/*genetics ; *Gene Expression Regulation ; Gene Rearrangement ; *Genes, Mitochondrial ; *Genome, Mitochondrial ; Mites/*genetics ; Nucleic Acid Conformation ; RNA, Transfer/*genetics ; Sequence Homology ; }, abstract = {BACKGROUND: Mitochondrial (mt) genomes of animals typically contain 37 genes for 13 proteins, two ribosomal RNA (rRNA) genes and 22 transfer RNA (tRNA) genes. In sarcoptiform mites, the entire set of mt tRNA genes is present in Aleuroglyphus ovatus, Caloglyphus berlesei, Dermatophagoides farinae, D. pteronyssinus, Histiostoma blomquisti and Psoroptes cuniculi. Loss of 16 mt tRNA genes, however, was reported in Steganacarus magnus; loss of 2-3 tRNA genes was reported in Tyrophagus longior, T. putrescentiae and Sarcoptes scabiei. Nevertheless, convincing evidence for mt gene loss is lacking in these mites.

RESULTS: We sequenced the mitochondrial genomes of two sarcoptiform mites, Histiostoma feroniarum (13,896 bp) and Rhizoglyphus robini (14,244 bp). Using tRNAScan and ARWEN programs, we identified 16 and 17 tRNA genes in the mt genomes of H. feroniarum and R. robini, respectively. The other six mt tRNA genes in H. feroniarum and five mt tRNA genes in R. robini can only be identified manually by sequence comparison when alternative anticodons are considered. We applied this manual approach to other mites that were reported previously to have lost mt tRNA genes. We were able to identify all of the 16 mt tRNA genes that were reported as lost in St. magnus, two of the three mt tRNA genes that were reported as lost in T. longior and T. putrescentiae, and the two mt tRNA genes that were reported as lost in Sa. scabiei. All of the tRNA genes inferred from these manually identified genes have truncation in the arms and mismatches in the stems.

CONCLUSIONS: Our results reveal very unconventional tRNA structures in sarcoptiform mites and do not support the loss of mt tRNA genes in these mites. The functional implication of the drastic structural changes in these tRNA genes remains to be investigated.}, } @article {pmid29914376, year = {2018}, author = {Gao, CF and Wu, XY}, title = {Feature extraction method for proteins based on Markov tripeptide by compressive sensing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {229}, pmid = {29914376}, issn = {1471-2105}, abstract = {BACKGROUND: In order to capture the vital structural information of the original protein, the symbol sequence was transformed into the Markov frequency matrix according to the consecutive three residues throughout the chain. A three-dimensional sparse matrix sized 20 × 20 × 20 was obtained and expanded to one-dimensional vector. Then, an appropriate measurement matrix was selected for the vector to obtain a compressed feature set by random projection. Consequently, the new compressive sensing feature extraction technology was proposed.

RESULTS: Several indexes were analyzed on the cell membrane, cytoplasm, and nucleus dataset to detect the discrimination of the features. In comparison with the traditional methods of scale wavelet energy and amino acid components, the experimental results suggested the advantage and accuracy of the features by this new method.

CONCLUSIONS: The new features extracted from this model could preserve the maximum information contained in the sequence and reflect the essential properties of the protein. Thus, it is an adequate and potential method in collecting and processing the protein sequence from a large sample size and high dimension.}, } @article {pmid29914375, year = {2018}, author = {Chatelain, C and Durand, G and Thuillier, V and Augé, F}, title = {Performance of epistasis detection methods in semi-simulated GWAS.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {231}, pmid = {29914375}, issn = {1471-2105}, abstract = {BACKGROUND: Part of the missing heritability in Genome Wide Association Studies (GWAS) is expected to be explained by interactions between genetic variants, also called epistasis. Various statistical methods have been developed to detect epistasis in case-control GWAS. These methods face major statistical challenges due to the number of tests required, the complexity of the Linkage Disequilibrium (LD) structure, and the lack of consensus regarding the definition of epistasis. Their limited impact in terms of uncovering new biological knowledge might be explained in part by the limited amount of experimental data available to validate their statistical performances in a realistic GWAS context. In this paper, we introduce a simulation pipeline for generating real scale GWAS data, including epistasis and realistic LD structure. We evaluate five exhaustive bivariate interaction methods, fastepi, GBOOST, SHEsisEpi, DSS, and IndOR. Two hundred thirty four different disease scenarios are considered in extensive simulations. We report the performances of each method in terms of false positive rate control, power, area under the ROC curve (AUC), and computation time using a GPU. Finally we compare the result of each methods on a real GWAS of type 2 diabetes from the Welcome Trust Case Control Consortium.

RESULTS: GBOOST, SHEsisEpi and DSS allow a satisfactory control of the false positive rate. fastepi and IndOR present an increase in false positive rate in presence of LD between causal SNPs, with our definition of epistasis. DSS performs best in terms of power and AUC in most scenarios with no or weak LD between causal SNPs. All methods can exhaustively analyze a GWAS with 6.105 SNPs and 15,000 samples in a couple of hours using a GPU.

CONCLUSION: This study confirms that computation time is no longer a limiting factor for performing an exhaustive search of epistasis in large GWAS. For this task, using DSS on SNP pairs with limited LD seems to be a good strategy to achieve the best statistical performance. A combination approach using both DSS and GBOOST is supported by the simulation results and the analysis of the WTCCC dataset demonstrated that this approach can detect distinct genes in epistasis. Finally, weak epistasis between common variants will be detectable with existing methods when GWAS of a few tens of thousands cases and controls are available.}, } @article {pmid29914374, year = {2018}, author = {Pinto, RA and Almeida-Santos, J and Lourenço, R and Saúde, L}, title = {Identification of Dmrt2a downstream genes during zebrafish early development using a timely controlled approach.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {14}, pmid = {29914374}, issn = {1471-213X}, support = {PTDC/SAU-BID/119627/2010//Fundação para a Ciência e a Tecnologia/International ; SFRH/BD/87607/2012//Fundação para a Ciência e a Tecnologia/International ; iFCT//Fundação para a Ciência e a Tecnologia/International ; LISBOA-01-0145-FEDER-007391//FEDER through POR Lisboa 2020 - Programa Operacional Regional de Lisboa, PORTUGAL 2020 and by Fundação para a Ciência e a Tecnologia/International ; }, abstract = {BACKGROUND: Dmrt2a is a zinc finger like transcription factor with several roles during zebrafish early development: left-right asymmetry, synchronisation of the somite clock genes and fast muscle differentiation. Despite the described functions, Dmrt2a mechanism of action is unknown. Therefore, with this work, we propose to identify Dmrt2a downstream genes during zebrafish early development.

RESULTS: We generated and validated a heat-shock inducible transgenic line, to timely control dmrt2a overexpression, and dmrt2a mutant lines. We characterised dmrt2a overexpression phenotype and verified that it was very similar to the one described after knockdown of this gene, with left-right asymmetry defects and desynchronisation of somite clock genes. Additionally, we identified a new phenotype of somite border malformation. We generated several dmrt2a mutant lines, but we only detected a weak to negligible phenotype. As dmrt2a has a paralog gene, dmrt2b, with similar functions and expression pattern, we evaluated the possibility of redundancy. We found that dmrt2b does not seem to compensate the lack of dmrt2a. Furthermore, we took advantage of one of our mutant lines to confirm dmrt2a morpholino specificity, which was previously shown to be a robust knockdown tool in two independent studies. Using the described genetic tools to perform and validate a microarray, we were able to identify six genes downstream of Dmrt2a: foxj1b, pxdc1b, cxcl12b, etv2, foxc1b and cyp1a.

CONCLUSIONS: In this work, we generated and validated several genetic tools for dmrt2a and identified six genes downstream of this transcription factor. The identified genes will be crucial to the future understanding of Dmrt2a mechanism of action in zebrafish.}, } @article {pmid29914373, year = {2018}, author = {Zhang, J and Li, Y and Liu, B and Wang, L and Zhang, L and Hu, J and Chen, J and Zheng, H and Lu, M}, title = {Characterization of the Populus Rab family genes and the function of PtRabE1b in salt tolerance.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {124}, pmid = {29914373}, issn = {1471-2229}, support = {31270699//National Natural Science Foundation of China/ ; }, mesh = {Chromosomes, Plant/genetics ; Conserved Sequence/genetics ; Genes, Plant/*genetics/physiology ; Phylogeny ; Plant Proteins/*genetics/physiology ; Populus/*genetics/physiology ; Promoter Regions, Genetic/genetics ; Salt Tolerance ; Salt-Tolerant Plants/*genetics/physiology ; Transcriptome ; rab GTP-Binding Proteins/*genetics/physiology ; }, abstract = {BACKGROUND: Rab proteins form the largest family of the Ras superfamily of small GTP-binding proteins and regulate intracellular trafficking pathways. However, the function of the Rab proteins in woody species is still an open question.

RESULTS: Here, a total of 67 PtRabs were identified in Populus trichocarpa and categorized into eight subfamilies (RabA-RabH). Based on their chromosomal distribution and duplication blocks in the Populus genome, a total of 27 PtRab paralogous pairs were identified and all of them were generated by whole-genome duplication events. Combined the expression correlation and duplication date, the PtRab paralogous pairs that still keeping highly similar expression patterns were generated around the latest large-scale duplication (~ 13 MYA). The cis-elements and co-expression network of unique expanded PtRabs suggest their potential roles in poplar development and environmental responses. Subcellular localization of PtRabs from each subfamily indicates each subfamily shows a localization pattern similar to what is revealed in Arabidopsis but RabC shows a localization different from their counterparts. Furthermore, we characterized PtRabE1b by overexpressing its constitutively active mutant PtRabE1b(Q74L) in poplar and found that PtRabE1b(Q74L) enhanced the salt tolerance.

CONCLUSIONS: These findings provide new insights into the functional divergence of PtRabs and resources for genetic engineering resistant breeding in tree species.}, } @article {pmid29914372, year = {2018}, author = {Duchene, S and Duchene, DA and Geoghegan, JL and Dyson, ZA and Hawkey, J and Holt, KE}, title = {Inferring demographic parameters in bacterial genomic data using Bayesian and hybrid phylogenetic methods.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {95}, pmid = {29914372}, issn = {1471-2148}, support = {//Wellcome Trust/United Kingdom ; 1061409//National Health and Medical Research Council/International ; 106158//Wellcome Trust (GB)/International ; McKenzie//University of Melbourne (AU)/International ; }, mesh = {Base Sequence ; Bayes Theorem ; Computer Simulation ; *Genome, Bacterial ; *Genomics ; Models, Genetic ; *Phylogeny ; Reproducibility of Results ; *Statistics as Topic ; Time Factors ; }, abstract = {BACKGROUND: Recent developments in sequencing technologies make it possible to obtain genome sequences from a large number of isolates in a very short time. Bayesian phylogenetic approaches can take advantage of these data by simultaneously inferring the phylogenetic tree, evolutionary timescale, and demographic parameters (such as population growth rates), while naturally integrating uncertainty in all parameters. Despite their desirable properties, Bayesian approaches can be computationally intensive, hindering their use for outbreak investigations involving genome data for a large numbers of pathogen isolates. An alternative to using full Bayesian inference is to use a hybrid approach, where the phylogenetic tree and evolutionary timescale are estimated first using maximum likelihood. Under this hybrid approach, demographic parameters are inferred from estimated trees instead of the sequence data, using maximum likelihood, Bayesian inference, or approximate Bayesian computation. This can vastly reduce the computational burden, but has the disadvantage of ignoring the uncertainty in the phylogenetic tree and evolutionary timescale.

RESULTS: We compared the performance of a fully Bayesian and a hybrid method by analysing six whole-genome SNP data sets from a range of bacteria and simulations. The estimates from the two methods were very similar, suggesting that the hybrid method is a valid alternative for very large datasets. However, we also found that congruence between these methods is contingent on the presence of strong temporal structure in the data (i.e. clocklike behaviour), which is typically verified using a date-randomisation test in a Bayesian framework. To reduce the computational burden of this Bayesian test we implemented a date-randomisation test using a rapid maximum likelihood method, which has similar performance to its Bayesian counterpart.

CONCLUSIONS: Hybrid approaches can produce reliable inferences of evolutionary timescales and phylodynamic parameters in a fraction of the time required for fully Bayesian analyses. As such, they are a valuable alternative in outbreak studies involving a large number of isolates.}, } @article {pmid29914370, year = {2018}, author = {Huang, N and Ling, H and Liu, F and Su, Y and Su, W and Mao, H and Zhang, X and Wang, L and Chen, R and Que, Y}, title = {Identification and evaluation of PCR reference genes for host and pathogen in sugarcane-Sporisorium scitamineum interaction system.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {479}, pmid = {29914370}, issn = {1471-2164}, support = {31671752//National Natural Science Foundation of China/ ; 3134006//National Natural Science Foundation of China/ ; 31101196//National Natural Science Foundation of China (CN)/ ; 2015J06006//Natural Science Foundation of Fujian Province/ ; CARS-17//Modern Agriculture Technology of China/ ; JA14095//New Century Excellent Talents in Fujian Province University/ ; KFA17267A//Special fund for science and technology innovation of Fujian Agriculture And Forestry University/ ; }, mesh = {Acyl-CoA Dehydrogenase/genetics/metabolism ; Gene Expression Regulation, Plant/genetics/physiology ; Host-Pathogen Interactions ; Plant Proteins/genetics/metabolism ; Polymerase Chain Reaction ; Saccharum/metabolism/*microbiology ; Ustilaginales/*pathogenicity ; }, abstract = {BACKGROUND: Sugarcane (Saccharum L. plant) is an important crop for sugar and bio-energy production around the world. Among sugarcane diseases, smut caused by Sporisorium scitamineum is one of the major fungal diseases causing severe losses to the sugarcane industry. The use of PCR reference genes is essential to the normalization of data on gene expression involving the sugarcane-S. scitamineum interaction system; however, no report that addresses criteria in selecting these reference genes has been published to date.

RESULTS: In this study, 10 sugarcane genes and eight S. scitamineum genes were selected as candidate PCR reference genes in the sugarcane-S. scitamineum interaction system. The stability and reliability of these 18 candidate genes were analyzed in smut-resistant (NCo376) and -susceptible (YC71-374) genotypes using the statistical algorithms geNorm, NormFinder, BestKeeper, and deltaCt method. Subsequently, the relative expression levels of the sugarcane chitinase I-3 gene and S. scitamineum chorismate mutase gene were determined to validate the applicability of these sugarcane and S. scitamineum PCR reference genes, respectively. We finally found that the acyl-CoA dehydrogenase gene (ACAD), serine/arginine repetitive matrix protein 1 gene (SARMp1), or their combination (ACAD + SARMp1) could be utilized as the most suitable reference genes for normalization of sugarcane gene expression in sugarcane bud tissues after S. scitamineum infection. Similarly, the inosine 5'-monophosphate dehydrogenase gene (S10), the SEC65-signal recognition particle subunit gene (S11), or their combination (S10 + S11) were suitable for normalization of S. scitamineum gene expression in sugarcane bud tissues.

CONCLUSIONS: The PCR reference genes ACAD, SARMp1, S10, and S11 may be employed in gene transcriptional studies involving the sugarcane-S. scitamineum interaction system.}, } @article {pmid29914369, year = {2018}, author = {Zhou, X and Batzoglou, S and Sidow, A and Zhang, L}, title = {HAPDeNovo: a haplotype-based approach for filtering and phasing de novo mutations in linked read sequencing data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {467}, pmid = {29914369}, issn = {1471-2164}, mesh = {Algorithms ; Computational Biology ; DNA Mutational Analysis ; *Genome, Human ; Genotype ; *Haplotypes ; High-Throughput Nucleotide Sequencing ; Humans ; *Mutation ; *Software ; }, abstract = {BACKGROUND: De novo mutations (DNMs) are associated with neurodevelopmental and congenital diseases, and their detection can contribute to understanding disease pathogenicity. However, accurate detection is challenging because of their small number relative to the genome-wide false positives in next generation sequencing (NGS) data. Software such as DeNovoGear and TrioDeNovo have been developed to detect DNMs, but at good sensitivity they still produce many false positive calls.

RESULTS: To address this challenge, we develop HAPDeNovo, a program that leverages phasing information from linked read sequencing, to remove false positive DNMs from candidate lists generated by DNM-detection tools. Short reads from each phasing block are allocated to each of the two haplotypes followed by generating a haploid genotype for each putative DNM. HAPDeNovo removes variants that are called as heterozygous in one of the haplotypes because they are almost certainly false positives. Our experiments on 10X Chromium linked read sequencing trio data reveal that HAPDeNovo eliminates 80 to 99% of false positives regardless of how large the candidate DNM set is.

CONCLUSIONS: HAPDeNovo leverages the haplotype information from linked read sequencing to remove spurious false positive DNMs effectively, and it increases accuracy of DNM detection dramatically without sacrificing sensitivity.}, } @article {pmid29914368, year = {2018}, author = {Bräuer, KE and Brockers, K and Moneer, J and Feuchtinger, A and Wollscheid-Lengeling, E and Lengeling, A and Wolf, A}, title = {Phylogenetic and genomic analyses of the ribosomal oxygenases Riox1 (No66) and Riox2 (Mina53) provide new insights into their evolution.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {96}, pmid = {29914368}, issn = {1471-2148}, support = {BO1748/12-1//Deutsche Forschungsgemeinschaft/International ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Nucleus/metabolism ; Chromosomal Proteins, Non-Histone/chemistry/*genetics ; Conserved Sequence ; *Evolution, Molecular ; *Genomics ; HeLa Cells ; Histone Demethylases/chemistry/genetics ; Humans ; Hydra ; Neoplasm Proteins/*genetics ; Nuclear Proteins/chemistry/genetics ; Oxygenases/chemistry/*genetics ; *Phylogeny ; Protein Domains ; Protein Transport ; Ribosomes/metabolism ; Species Specificity ; }, abstract = {BACKGROUND: Translation of specific mRNAs can be highly regulated in different cells, tissues or under pathological conditions. Ribosome heterogeneity can originate from variable expression or post-translational modifications of ribosomal proteins. The ribosomal oxygenases RIOX1 (NO66) and RIOX2 (MINA53) modify ribosomal proteins by histidine hydroxylation. A similar mechanism is present in prokaryotes. Thus, ribosome hydroxylation may be a well-conserved regulatory mechanism with implications in disease and development. However, little is known about the evolutionary history of Riox1 and Riox2 genes and their encoded proteins across eukaryotic taxa.

RESULTS: In this study, we have analysed Riox1 and Riox2 orthologous genes from 49 metazoen species and have constructed phylogenomic trees for both genes. Our genomic and phylogenetic analyses revealed that Arthropoda, Annelida, Nematoda and Mollusca lack the Riox2 gene, although in the early phylum Cnidaria both genes, Riox1 and Riox2, are present and expressed. Riox1 is an intronless single-exon-gene in several species, including humans. In contrast to Riox2, Riox1 is ubiquitously present throughout the animal kingdom suggesting that Riox1 is the phylogenetically older gene from which Riox2 has evolved. Both proteins have maintained a unique protein architecture with conservation of active sites within the JmjC domains, a dimerization domain, and a winged-helix domain. In addition, Riox1 proteins possess a unique N-terminal extension domain. Immunofluorescence analyses in Hela cells and in Hydra vulgaris identified a nucleolar localisation signal within the extended N-terminal domain of human RIOX1 and an altered subnuclear localisation for the Hydra Riox2.

CONCLUSIONS: Conserved active site residues and uniform protein domain architecture suggest a consistent enzymatic activity within the Riox orthologs throughout evolution. However, differences in genomic architecture, like single exon genes and alterations in subnuclear localisation, as described for Hydra, point towards adaption mechanisms that may correlate with taxa- or species-specific requirements. The diversification of Riox1/Riox2 gene structures throughout evolution suggest that functional requirements in expression of protein isoforms and/or subcellular localisation of proteins may have evolved by adaptation to lifestyle.}, } @article {pmid29914367, year = {2018}, author = {Lu, Z and Huang, Q and Zhang, T and Hu, B and Chang, Y}, title = {Global transcriptome analysis and characterization of Dryopteris fragrans (L.) Schott sporangium in different developmental stages.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {471}, pmid = {29914367}, issn = {1471-2164}, support = {31570189//National Natural Science Foundation of China/ ; }, mesh = {Databases, Protein ; Dryopteris/*genetics/*growth & development ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; High-Throughput Nucleotide Sequencing ; Molecular Sequence Annotation ; Plant Proteins/*genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Dryopteris fragrans (D. fragrans) is a potential medicinal fern distributed in volcanic magmatic rock areas under tough environmental condition. Sporangia are important organs for fern reproduction. This study was designed to characterize the transcriptome characteristics of the wild D. fragrans sporangia in three stages (stage A, B, and C) with the aim of uncovering its molecular mechanism of growth and development.

RESULTS: Using a HiSeq 4000, 79.81 Gb clean data (each sample is at least 7.95 GB) were obtained from nine samples, with three being supplied from each period, and assembled into 94,705 Unigenes, among which 44,006 Unigenes were annotated against public protein databases (NR, Swiss-Prot, KEGG, COG, KOG, GO, eggNOG and Pfam). Furthermore, we observed 7126 differentially expressed genes (DEG) (Fold Change > 4, FDR < 0.001), 349,885 SNP loci, and 10,584 SSRs. DEGs involved in DNA replication and homologous recombination were strongly expressed in stage A, and several DEGs involved in cutin, suberin and wax biosynthesis had undergone dramatic changes during development, which was consistent with morphological observations. DEGs responsible for secondary metabolism and plant hormone signal transduction changed clearly in the last two stages. DEGs homologous to those known genes associated with the development of reproductive organs of flowering plants have also been validated and discussed, such as AGL61, AGL62, ONAC010. In particular, a Unigene encoding TFL1, an important flower-development regulator in flowering plants, was identified and exhibited the highest expression level in stage B in D. fragrans sporangia.

CONCLUSIONS: This study is the first report on global transcriptome analysis in the development of sporangia of wild D. fragrans. DEGs related to development and homologous to flower-seed development in flowering plants were discussed. All DEGs involved in DNA replication and homologous recombination were consistent with morphological observations of paraffin slices. The results of this study provide rare resources for further investigation of the D. fragrans sporangium development, stress resistance and secondary metabolism.}, } @article {pmid29914366, year = {2018}, author = {Trizzino, M and Kapusta, A and Brown, CD}, title = {Transposable elements generate regulatory novelty in a tissue-specific fashion.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {468}, pmid = {29914366}, issn = {1471-2164}, mesh = {Binding Sites ; *DNA Transposable Elements ; *Gene Expression Regulation ; Humans ; *Nucleotide Motifs ; Organ Specificity ; *Regulatory Sequences, Nucleic Acid ; Terminal Repeat Sequences ; Transcription Factors/genetics/*metabolism ; }, abstract = {BACKGROUND: Transposable elements (TE) are an important source of evolutionary novelty in gene regulation. However, the mechanisms by which TEs contribute to gene expression are largely uncharacterized.

RESULTS: Here, we leverage Roadmap and GTEx data to investigate the association of TEs with active and repressed chromatin in 24 tissues. We find 112 human TE families enriched in active regions of the genome across tissues. Short Interspersed Nuclear Elements (SINEs) and DNA transposons are the most frequently enriched classes, while Long Terminal Repeat Retrotransposons (LTRs) are often enriched in a tissue-specific manner. We report across-tissue variability in TE enrichment in active regions. Genes with consistent expression across tissues are less likely to be associated with TE insertions. TE presence in repressed regions similarly follows tissue-specific patterns. Moreover, different TE classes correlate with different repressive marks: LTRs and Long Interspersed Nuclear Elements (LINEs) are overrepresented in regions marked by H3K9me3, while the other TEs are more likely to overlap regions with H3K27me3. Young TEs are typically enriched in repressed regions and depleted in active regions. We detect multiple instances of TEs that are enriched in tissue-specific active regulatory regions. Such TEs contain binding sites for transcription factors that are master regulators for the given tissue. These TEs are enriched in intronic enhancers, and their tissue-specific enrichment correlates with tissue-specific variations in the expression of the nearest genes.

CONCLUSIONS: We provide an integrated overview of the contribution of TEs to human gene regulation. Expanding previous analyses, we demonstrate that TEs can potentially contribute to the turnover of regulatory sequences in a tissue-specific fashion.}, } @article {pmid29914365, year = {2018}, author = {Kobayashi, Y and Maeda, T and Yamaguchi, K and Kameoka, H and Tanaka, S and Ezawa, T and Shigenobu, S and Kawaguchi, M}, title = {The genome of Rhizophagus clarus HR1 reveals a common genetic basis for auxotrophy among arbuscular mycorrhizal fungi.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {465}, pmid = {29914365}, issn = {1471-2164}, support = {JPMJAC1403//Accelerated Innovation Research Initiative Turning Top Science and Ideas into High-Impact Values/ ; }, mesh = {Computational Biology ; DNA, Fungal/genetics ; Daucus carota/microbiology ; Fungal Proteins/*genetics ; *Gene Expression Regulation, Plant ; *Genome, Fungal ; Glomeromycota/classification/*genetics/growth & development/isolation & purification ; High-Throughput Nucleotide Sequencing ; Mycorrhizae/*genetics ; Plant Roots/*microbiology ; Sequence Analysis, DNA ; Symbiosis ; }, abstract = {BACKGROUND: Mycorrhizal symbiosis is one of the most fundamental types of mutualistic plant-microbe interaction. Among the many classes of mycorrhizae, the arbuscular mycorrhizae have the most general symbiotic style and the longest history. However, the genomes of arbuscular mycorrhizal (AM) fungi are not well characterized due to difficulties in cultivation and genetic analysis. In this study, we sequenced the genome of the AM fungus Rhizophagus clarus HR1, compared the sequence with the genome sequence of the model species R. irregularis, and checked for missing genes that encode enzymes in metabolic pathways related to their obligate biotrophy.

RESULTS: In the genome of R. clarus, we confirmed the absence of cytosolic fatty acid synthase (FAS), whereas all mitochondrial FAS components were present. A KEGG pathway map identified the absence of genes encoding enzymes for several other metabolic pathways in the two AM fungi, including thiamine biosynthesis and the conversion of vitamin B6 derivatives. We also found that a large proportion of the genes encoding glucose-producing polysaccharide hydrolases, that are present even in ectomycorrhizal fungi, also appear to be absent in AM fungi.

CONCLUSIONS: In this study, we found several new genes that are absent from the genomes of AM fungi in addition to the genes previously identified as missing. Missing genes for enzymes in primary metabolic pathways imply that AM fungi may have a higher dependency on host plants than other biotrophic fungi. These missing metabolic pathways provide a genetic basis to explore the physiological characteristics and auxotrophy of AM fungi.}, } @article {pmid29914364, year = {2018}, author = {Kennedy, EM and Goehring, GN and Nichols, MH and Robins, C and Mehta, D and Klengel, T and Eskin, E and Smith, AK and Conneely, KN}, title = {An integrated -omics analysis of the epigenetic landscape of gene expression in human blood cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {476}, pmid = {29914364}, issn = {1471-2164}, support = {UL1TR000454//National Center for Advancing Translational Sciences/ ; T32GM008490//National Institute of General Medical Sciences/ ; UL1 TR000454/TR/NCATS NIH HHS/United States ; 1008188//Burroughs Wellcome Fund/ ; T32 GM008490/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Blood Cells/*metabolism ; Cohort Studies ; CpG Islands ; *DNA Methylation ; *Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Gene Ontology ; Genomics ; Humans ; Male ; Middle Aged ; Young Adult ; }, abstract = {BACKGROUND: Gene expression can be influenced by DNA methylation 1) distally, at regulatory elements such as enhancers, as well as 2) proximally, at promoters. Our current understanding of the influence of distal DNA methylation changes on gene expression patterns is incomplete. Here, we characterize genome-wide methylation and expression patterns for ~ 13 k genes to explore how DNA methylation interacts with gene expression, throughout the genome.

RESULTS: We used a linear mixed model framework to assess the correlation of DNA methylation at ~ 400 k CpGs with gene expression changes at ~ 13 k transcripts in two independent datasets from human blood cells. Among CpGs at which methylation significantly associates with transcription (eCpGs), > 50% are distal (> 50 kb) or trans (different chromosome) to the correlated gene. Many eCpG-transcript pairs are consistent between studies and ~ 90% of neighboring eCpGs associate with the same gene, within studies. We find that enhancers (P < 5e-18) and microRNA genes (P = 9e-3) are overrepresented among trans eCpGs, and insulators and long intergenic non-coding RNAs are enriched among cis and distal eCpGs. Intragenic-eCpG-transcript correlations are negative in 60-70% of occurrences and are enriched for annotated gene promoters and enhancers (P < 0.002), highlighting the importance of intragenic regulation. Gene Ontology analysis indicates that trans eCpGs are enriched for transcription factor genes and chromatin modifiers, suggesting that some trans eCpGs represent the influence of gene networks and higher-order transcriptional control.

CONCLUSIONS: This work sheds new light on the interplay between epigenetic changes and gene expression, and provides useful data for mining biologically-relevant results from epigenome-wide association studies.}, } @article {pmid29914363, year = {2018}, author = {Dunning Hotopp, JC}, title = {Grafting or pruning in the animal tree: lateral gene transfer and gene loss?.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {470}, pmid = {29914363}, issn = {1471-2164}, support = {R01 CA206188/CA/NCI NIH HHS/United States ; ABI-1457957//National Science Foundation/ ; 1-R01-CA206188//National Cancer Institute/ ; }, mesh = {Animals ; Bacteria/*genetics ; Eukaryota/*genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; *Genome ; Humans ; Phylogeny ; Prokaryotic Cells/*metabolism ; }, abstract = {BACKGROUND: Lateral gene transfer (LGT), also known as horizontal gene transfer, into multicellular eukaryotes with differentiated tissues, particularly gonads, continues to be met with skepticism by many prominent evolutionary and genomic biologists. A detailed examination of 26 animal genomes identified putative LGTs in invertebrate and vertebrate genomes, concluding that there are fewer predicted LGTs in vertebrates/chordates than invertebrates, but there is still evidence of LGT into chordates, including humans. More recently, a reanalysis of a subset of these putative LGTs into vertebrates concluded that there is not horizontal gene transfer in the human genome. One of the genes in dispute is an N-acyl-aromatic-L-amino acid amidohydrolase (ENSG00000132744), which encodes ACY3. This gene was initially identified as a putative bacteria-chordate LGT but was later debunked as it has a significant BLAST match to a more recently deposited genome of Saccoglossus kowalevskii, a flatworm, Metazoan, and hemichordate.

RESULTS: Using BLAST searches, HMM searches, and phylogenetics to assess the evidence for LGT, gene loss, and rate variation in ACY3/ASPA homologues, the most parsimonious explanation for the distribution of ACY3/ASPA genes in eukaryotes involves both gene loss and bacteria-animal LGT, albeit LGT that occurred hundreds of millions of years ago prior to the divergence of gnathostomes.

CONCLUSIONS: ACY3/ASPA is most likely a bacteria-animal LGT. LGTs at these time scales in the ancestors of humans are not unexpected given the many known, well-characterized, and adaptive LGTs from bacteria to insects and nematodes.}, } @article {pmid29914362, year = {2018}, author = {Qian, Y and Zhang, S and Yao, S and Xia, J and Li, Y and Dai, X and Wang, W and Jiang, X and Liu, Y and Li, M and Gao, L and Xia, T}, title = {Effects of vitro sucrose on quality components of tea plants (Camellia sinensis) based on transcriptomic and metabolic analysis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {121}, pmid = {29914362}, issn = {1471-2229}, support = {31570694//Natural Science Foundation of China/ ; 31470689//Natural Science Foundation of China/ ; 31300577//Natural Science Foundation of China/ ; 20133418130001//Specialized Research Fund for the Doctoral Program of Higher Education/ ; 1408085QC51//Natural Science Foundation of Anhui Province, China/ ; KJ2017A441//Natural Science Foundation for Higher Education of Anhui Province/ ; 2016jb02//Natural Science Foundation of Suzhou University/ ; }, mesh = {Camellia sinensis/drug effects/genetics/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Plant/drug effects ; Genes, Plant/genetics ; Metabolomics ; Polyphenols/metabolism ; Real-Time Polymerase Chain Reaction ; Sucrose/metabolism/*pharmacology ; Transcription Factors/metabolism ; Volatile Organic Compounds/metabolism ; }, abstract = {BACKGROUND: Tea plants [Camellia sinensis (L.) O. Kuntze] can produce one of the three most widely popular non-alcoholic beverages throughout the world. Polyphenols and volatiles are the main functional ingredients determining tea's quality and flavor; however, the biotic or abiotic factors affecting tea polyphenol biosynthesis are unclear. This paper focuses on the molecular mechanisms of sucrose on polyphenol biosynthesis and volatile composition variation in tea plants.

RESULTS: Metabolic analysis showed that the total content of anthocyanins, catechins, and proanthocyanidins(PAs) increased with sucrose, and they accumulated most significantly after 14 days of treatment. Transcriptomic analysis revealed 8384 and 5571 differentially expressed genes in 2-day and 14-day sucrose-treated tea plants compared with control-treated plants. Most of the structural genes and transcription factors (TFs) involved in polyphenol biosynthesis were significantly up-regulated after 2d. Among these transcripts, the predicted genes encoding glutathione S-transferase (GST), ATP-binding cassette transporters (ABC transporters), and multidrug and toxic compound extrusion transporters (MATE transporters) appeared up regulated. Correspondingly, ultra-performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-QQQ-MS/MS) analysis revealed that the content of non-galloylated catechins and oligomeric PAs decreased in the upper-stem and increased in the lower-stem significantly, especially catechin (C), epicatechin (EC), and their oligomeric PAs. This result suggests that the related flavonoids were transported downward in the stem by transporters. GC/MS data implied that four types of volatile compounds, namely terpene derivatives, aromatic derivatives, lipid derivatives, and others, were accumulated differently after in vitro sucrose treatment.

CONCLUSIONS: Our data demonstrated that sucrose regulates polyphenol biosynthesis in Camellia sinensis by altering the expression of transcription factor genes and pathway genes. Additionally, sucrose promotes the transport of polyphenols and changes the aroma composition in tea plant.}, } @article {pmid29914361, year = {2018}, author = {Xue, H and Zhang, P and Shi, T and Yang, J and Wang, L and Wang, S and Su, Y and Zhang, H and Qiao, Y and Li, X}, title = {Genome-wide characterization of simple sequence repeats in Pyrus bretschneideri and their application in an analysis of genetic diversity in pear.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {473}, pmid = {29914361}, issn = {1471-2164}, support = {172102110244//Science-Technology Project of Henan province/ ; 1610192017709//Central Public-Interest Scientific Institution Basal Research Fund/ ; 31272140//National Natural Science Foundation of China/ ; CAAS-ASTIP//Agricultural Science and Technology Innovation Program (ASTIP)/ ; }, mesh = {China ; Chromosome Mapping ; DNA, Plant ; Genetic Linkage ; *Genetic Variation ; *Genome, Plant ; *Microsatellite Repeats ; Phylogeny ; Polymorphism, Genetic ; Pyrus/*genetics ; }, abstract = {BACKGROUND: Pear (Pyrus spp.) is an economically important temperate fruit tree worldwide. In the past decade, significant progress has been made in pear molecular genetics based on DNA research, but the number of molecular markers is still quite limited, which hardly satisfies the increasing needs of geneticists and breeders.

RESULTS: In this study, a total of 156,396 simple sequence repeat (SSR) loci were identified from a genome sequence of Pyrus bretschneideri 'Dangshansuli'. A total of 101,694 pairs of SSR primers were designed from the SSR loci, and 80,415 of the SSR loci were successfully located on 17 linkage groups (LGs). A total of 534 primer pairs were synthesized and preliminarily screened in four pear cultivars, and of these, 332 primer pairs were selected as clear, stable, and polymorphic SSR markers. Eighteen polymorphic SSR markers were randomly selected from the 332 polymorphic SSR markers in order to perform a further analysis of the genetic diversity among 44 pear cultivars. The 14 European pears and their hybrid materials were clustered into one group (European pear group); 29 Asian pear cultivars were clustered into one group (Asian pear group); and the Zangli pear cultivar 'Deqinli' from Yunnan Province, China, was grouped in an independent group, which suggested that the cultivar 'Deqinli' is a distinct and valuable germplasm resource. The population structure analysis partitioned the 44 cultivars into two populations, Pop 1 and Pop 2. Pop 2 was further divided into two subpopulations. Results from the population structure analysis were generally consistent with the results from the UPGMA cluster analysis.

CONCLUSIONS: The results of the present study showed that the use of next-generating sequencing to develop SSR markers is fast and effective, and the developed SSR markers can be utilized by researchers and breeders for future pear improvement.}, } @article {pmid29914360, year = {2018}, author = {Yu, Q and Wei, D and Huo, H}, title = {SamSelect: a sample sequence selection algorithm for quorum planted motif search on large DNA datasets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {228}, pmid = {29914360}, issn = {1471-2105}, abstract = {BACKGROUND: Given a set of t n-length DNA sequences, q satisfying 0 < q ≤ 1, and l and d satisfying 0 ≤ d < l < n, the quorum planted motif search (qPMS) finds l-length strings that occur in at least qt input sequences with up to d mismatches and is mainly used to locate transcription factor binding sites in DNA sequences. Existing qPMS algorithms have been able to efficiently process small standard datasets (e.g., t = 20 and n = 600), but they are too time consuming to process large DNA datasets, such as ChIP-seq datasets that contain thousands of sequences or more.

RESULTS: We analyze the effects of t and q on the time performance of qPMS algorithms and find that a large t or a small q causes a longer computation time. Based on this information, we improve the time performance of existing qPMS algorithms by selecting a sample sequence set D' with a small t and a large q from the large input dataset D and then executing qPMS algorithms on D'. A sample sequence selection algorithm named SamSelect is proposed. The experimental results on both simulated and real data show (1) that SamSelect can select D' efficiently and (2) that the qPMS algorithms executed on D' can find implanted or real motifs in a significantly shorter time than when executed on D.

CONCLUSIONS: We improve the ability of existing qPMS algorithms to process large DNA datasets from the perspective of selecting high-quality sample sequence sets so that the qPMS algorithms can find motifs in a short time in the selected sample sequence set D', rather than take an unfeasibly long time to search the original sequence set D. Our motif discovery method is an approximate algorithm.}, } @article {pmid29914359, year = {2018}, author = {Si, Y and Wen, H and Li, Y and He, F and Li, J and Li, S and He, H}, title = {Liver transcriptome analysis reveals extensive transcriptional plasticity during acclimation to low salinity in Cynoglossus semilaevis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {464}, pmid = {29914359}, issn = {1471-2164}, support = {2012AA10A403//Ministry of Science and Technology of the People's Republic of China/ ; 4147611//National Natural Science Foundation of China/ ; 201712026//Ministry of Education of the People's Republic of China/ ; }, mesh = {Acclimatization ; Animals ; Fish Proteins/*genetics ; Flatfishes/*genetics/physiology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genome ; High-Throughput Nucleotide Sequencing ; Liver/*metabolism ; Salinity ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: Salinity is an important abiotic stress that influences the physiological and metabolic activity, reproduction, growth and development of marine fish. It has been suggested that half-smooth tongue sole (Cynoglossus semilaevis), a euryhaline fish species, uses a large amount of energy to maintain osmotic pressure balance when exposed to fluctuations in salinity. To delineate the molecular response of C. semilaevis to different levels of salinity, we performed RNA-seq analysis of the liver to identify the genes and molecular and biological processes involved in responding to salinity changes.

RESULTS: The present study yielded 330.4 million clean reads, of which 83.9% were successfully mapped to the reference genome of C. semilaevis. One hundred twenty-eight differentially expressed genes (DEGs), including 43 up-regulated genes and 85 down-regulated genes, were identified. These DEGs were highly represented in metabolic pathways, steroid biosynthesis, terpenoid backbone biosynthesis, butanoate metabolism, glycerolipid metabolism and the 2-oxocarboxylic acid metabolism pathway. In addition, genes involved in metabolism, osmoregulation and ion transport, signal transduction, immune response and stress response, and cytoskeleton remodeling were affected during acclimation to low salinity. Genes acat2, fdps, hmgcr, hmgcs1, mvk, pmvk, ebp, lss, dhcr7, and dhcr24 were up-regulated and abat, ddc, acy1 were down-regulated in metabolic pathways. Genes aqp10 and slc6a6 were down-regulated in osmoregulation and ion transport. Genes abat, fdps, hmgcs1, mvk, pmvk and dhcr7 were first reported to be associated with salinity adaptation in teleosts.

CONCLUSIONS: Our results revealed that metabolic pathways, especially lipid metabolism were important for salinity adaptation. The candidate genes identified from this study provide a basis for further studies to investigate the molecular mechanism of salinity adaptation and transcriptional plasticity in marine fish.}, } @article {pmid29914358, year = {2018}, author = {Yu, B and Li, S and Qiu, W and Wang, M and Du, J and Zhang, Y and Chen, X}, title = {Prediction of subcellular location of apoptosis proteins by incorporating PsePSSM and DCCA coefficient based on LFDA dimensionality reduction.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {478}, pmid = {29914358}, issn = {1471-2164}, support = {51372125 and 51572136//National Natural Science Foundation of China/ ; J17KA159//Project of Shandong Province Higher Educational Science and Technology Program/ ; ZR2018MC007//Natural Science Foundation of Shandong Province of China/ ; }, mesh = {Algorithms ; Apoptosis Regulatory Proteins/*analysis/chemistry ; Correlation of Data ; Discriminant Analysis ; Sequence Analysis, Protein/*methods ; }, abstract = {BACKGROUND: Apoptosis is associated with some human diseases, including cancer, autoimmune disease, neurodegenerative disease and ischemic damage, etc. Apoptosis proteins subcellular localization information is very important for understanding the mechanism of programmed cell death and the development of drugs. Therefore, the prediction of subcellular localization of apoptosis protein is still a challenging task.

RESULTS: In this paper, we propose a novel method for predicting apoptosis protein subcellular localization, called PsePSSM-DCCA-LFDA. Firstly, the protein sequences are extracted by combining pseudo-position specific scoring matrix (PsePSSM) and detrended cross-correlation analysis coefficient (DCCA coefficient), then the extracted feature information is reduced dimensionality by LFDA (local Fisher discriminant analysis). Finally, the optimal feature vectors are input to the SVM classifier to predict subcellular location of the apoptosis proteins. The overall prediction accuracy of 99.7, 99.6 and 100% are achieved respectively on the three benchmark datasets by the most rigorous jackknife test, which is better than other state-of-the-art methods.

CONCLUSION: The experimental results indicate that our method can significantly improve the prediction accuracy of subcellular localization of apoptosis proteins, which is quite high to be able to become a promising tool for further proteomics studies. The source code and all datasets are available at https://github.com/QUST-BSBRC/PsePSSM-DCCA-LFDA/ .}, } @article {pmid29914357, year = {2018}, author = {Luo, Q and Guo, C and Zhang, YJ and Cai, Y and Liu, G}, title = {Algorithms designed for compressed-gene-data transformation among gene banks with different references.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {230}, pmid = {29914357}, issn = {1471-2105}, abstract = {BACKGROUND: With the reduction of gene sequencing cost and demand for emerging technologies such as precision medical treatment and deep learning in genome, it is an era of gene data outbreaks today. How to store, transmit and analyze these data has become a hotspot in the current research. Now the compression algorithm based on reference is widely used due to its high compression ratio. There exists a big problem that the data from different gene banks can't merge directly and share information efficiently, because these data are usually compressed with different references. The traditional workflow is decompression-and-recompression, which is too simple and time-consuming. We should improve it and speed it up.

RESULTS: In this paper, we focus on this problem and propose a set of transformation algorithms to cope with it. We will 1) analyze some different compression algorithms to find the similarities and the differences among all of them, 2) come up with a naïve method named TDM for data transformation between difference gene banks and finally 3) optimize former method TDM and propose the method named TPI and the method named TGI. A number of experiment result proved that the three algorithms we proposed are an order of magnitude faster than traditional decompression-and-recompression workflow.

CONCLUSIONS: Firstly, the three algorithms we proposed all have good performance in terms of time. Secondly, they have their own different advantages faced with different dataset or situations. TDM and TPI are more suitable for small-scale gene data transformation, while TGI is more suitable for large-scale gene data transformation.}, } @article {pmid29914356, year = {2018}, author = {Zhang, YJ and Zhu, C and Ding, Y and Yan, ZW and Li, GH and Lan, Y and Wen, JF and Chen, B}, title = {Subcellular stoichiogenomics reveal cell evolution and electrostatic interaction mechanisms in cytoskeleton.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {469}, pmid = {29914356}, issn = {1471-2164}, support = {31672363//National Natural Science Foundation of China/ ; 31572256//National Natural Science Foundation of China/ ; 31372265//National Natural Science Foundation of China/ ; KJ1600304//Chongqing Municipal Education Commission/ ; }, mesh = {Amino Acids/analysis ; Animals ; *Biological Evolution ; Cell Nucleus/metabolism ; Computational Biology ; Cytoskeletal Proteins/*metabolism ; Cytoskeleton/*physiology ; Eukaryotic Cells/metabolism ; Genomics/*methods ; Humans ; Hydrogen/analysis ; Nitrogen/analysis ; Prokaryotic Cells/metabolism ; Protein Interaction Maps ; Proteome/*analysis ; Selection, Genetic ; *Static Electricity ; Subcellular Fractions ; Sulfur/analysis ; }, abstract = {BACKGROUND: Eukaryotic cells contain a huge variety of internally specialized subcellular compartments. Stoichiogenomics aims to reveal patterns of elements usage in biological macromolecules. However, the stoichiogenomic characteristics and how they adapt to various subcellular microenvironments are still unknown.

RESULTS: Here we first updated the definition of stoichiogenomics. Then we applied it to subcellular research, and detected distinctive nitrogen content of nuclear and hydrogen, sulfur content of extracellular proteomes. Specially, we found that acidic amino acids (AAs) content of cytoskeletal proteins is the highest. The increased charged AAs are mainly caused by the eukaryotic originated cytoskeletal proteins. Functional subdivision of the cytoskeleton showed that activation, binding/association, and complexes are the three largest functional categories. Electrostatic interaction analysis showed an increased electrostatic interaction between both primary sequences and PPI interfaces of 3D structures, in the cytoskeleton.

CONCLUSIONS: This study creates a blueprint of subcellular stoichiogenomic characteristics, and explains that charged AAs of the cytoskeleton increased greatly in evolution, which offer material basis for the eukaryotic cytoskeletal proteins to act in two ways of electrostatic interactions, and further perform their activation, binding/association and complex formation.}, } @article {pmid29914355, year = {2018}, author = {Cserhati, MF and Mooter, ME and Peterson, L and Wicks, B and Xiao, P and Pauley, M and Guda, C}, title = {Motifome comparison between modern human, Neanderthal and Denisovan.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {472}, pmid = {29914355}, issn = {1471-2164}, support = {P20 GM103427/GM/NIGMS NIH HHS/United States ; P30 CA036727/CA/NCI NIH HHS/United States ; 2P20GM103427//Nebraska INBRE/ ; 5P30CA036727//CCSG award/ ; }, mesh = {Animals ; Endogenous Retroviruses/genetics ; *Fossils ; *Genome ; Humans ; Neanderthals/*genetics ; Nucleotide Motifs/*genetics ; Phenotype ; Promoter Regions, Genetic ; Trans-Activators ; }, abstract = {BACKGROUND: The availability of the genomes of two archaic humans, Neanderthal and Denisovan, and that of modern humans provides researchers an opportunity to investigate genetic differences between these three subspecies on a genome-wide scale. Here we describe an algorithm that predicts statistically significant motifs based on the difference between a given motif's actual and expected distributions. The algorithm was previously applied to plants but was modified for this work.

RESULTS: The result of applying the algorithm to the human, Neanderthal, and Denisovan genomes is a catalog of potential regulatory motifs in these three human subspecies. We examined the distributions of these motifs in genetic elements including human retroviruses, human accelerated regions, and human accelerated conserved noncoding sequences regions. Differences in these distributions could be the origin of differences in phenotype between the three subspecies. Twenty significant motifs common to all three genomes were found; thirty-three were found in endogenous retroviruses in Neanderthal and Denisovan. Ten of these motifs mapped to the 22 bp core of MiR-1304. The core of this genetic element regulates the ENAM and AMTN genes, which take part in odontogenesis and whose 3' UTRs contained significant motifs. The introns of 20 genes were found to contain a large number of significant motifs, which were also overrepresented in 49 human accelerated regions. These genes include NAV2, SorCS2, TRAPPC9, GRID1, PRDM16, CAMTA1, and ASIC which are all involved in neuroregulation. Further analysis of these genes using the GO database indicates that many are associated with neurodevelopment. Also, varying numbers of significant motifs were found to occur in regions of the Neanderthal and Denisovan genomes that are missing from the human genome, suggesting further functional differences between modern and archaic humans.

CONCLUSION: Although Neanderthal and Denisovan are now extinct, detailed examination of elements from their genomes can shed light on possible phenotypic and cognitive differences between these two archaic human subspecies and modern humans. Genetic similarities and differences between these three subspecies and other fossil hominids would also be of interest.}, } @article {pmid29914354, year = {2018}, author = {Street, K and Risso, D and Fletcher, RB and Das, D and Ngai, J and Yosef, N and Purdom, E and Dudoit, S}, title = {Slingshot: cell lineage and pseudotime inference for single-cell transcriptomics.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {477}, pmid = {29914354}, issn = {1471-2164}, support = {K01 AG045344/AG/NIA NIH HHS/United States ; T32 HG000047/HG/NHGRI NIH HHS/United States ; S10RR029668//National Center for Research Resources/ ; U01 MH105979/MH/NIMH NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; T32HG000047//National Human Genome Research Institute/ ; U01MH105979//National Institute of Mental Health/ ; K01AG045344//National Institute on Aging/ ; R01 DC007235/DC/NIDCD NIH HHS/United States ; RO1DC007235//National Institute on Deafness and Other Communication Disorders/ ; }, mesh = {*Cell Lineage ; Cluster Analysis ; Gene Expression Profiling/*methods ; Humans ; Myoblasts, Skeletal/metabolism ; Single-Cell Analysis ; Software ; }, abstract = {BACKGROUND: Single-cell transcriptomics allows researchers to investigate complex communities of heterogeneous cells. It can be applied to stem cells and their descendants in order to chart the progression from multipotent progenitors to fully differentiated cells. While a variety of statistical and computational methods have been proposed for inferring cell lineages, the problem of accurately characterizing multiple branching lineages remains difficult to solve.

RESULTS: We introduce Slingshot, a novel method for inferring cell lineages and pseudotimes from single-cell gene expression data. In previously published datasets, Slingshot correctly identifies the biological signal for one to three branching trajectories. Additionally, our simulation study shows that Slingshot infers more accurate pseudotimes than other leading methods.

CONCLUSIONS: Slingshot is a uniquely robust and flexible tool which combines the highly stable techniques necessary for noisy single-cell data with the ability to identify multiple trajectories. Accurate lineage inference is a critical step in the identification of dynamic temporal gene expression.}, } @article {pmid29914352, year = {2018}, author = {Roquigny, R and Novinscak, A and Arseneault, T and Joly, DL and Filion, M}, title = {Transcriptome alteration in Phytophthora infestans in response to phenazine-1-carboxylic acid production by Pseudomonas fluorescens strain LBUM223.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {474}, pmid = {29914352}, issn = {1471-2164}, mesh = {Biological Control Agents ; Gene Expression Profiling ; Phenazines/metabolism ; Phytophthora infestans/*genetics/growth & development/metabolism ; Pseudomonas fluorescens/*metabolism ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: Phytophthora infestans is responsible for late blight, one of the most important potato diseases. Phenazine-1-carboxylic acid (PCA)-producing Pseudomonas fluorescens strain LBUM223 isolated in our laboratory shows biocontrol potential against various plant pathogens. To characterize the effect of LBUM223 on the transcriptome of P. infestans, we conducted an in vitro time-course study. Confrontational assay was performed using P. infestans inoculated alone (control) or with LBUM223, its phzC- isogenic mutant (not producing PCA), or exogenically applied PCA. Destructive sampling was performed at 6, 9 and 12 days and the transcriptome of P. infestans was analysed using RNA-Seq. The expression of a subset of differentially expressed genes was validated by RT-qPCR.

RESULTS: Both LBUM223 and exogenically applied PCA significantly repressed P. infestans' growth at all times. Compared to the control treatment, transcriptomic analyses showed that the percentages of all P. infestans' genes significantly altered by LBUM223 and exogenically applied PCA increased as time progressed, from 50 to 61% and from to 32 to 46%, respectively. When applying an absolute cut-off value of 3 fold change or more for all three harvesting times, 207 genes were found significantly differentially expressed by PCA, either produced by LBUM223 or exogenically applied. Gene ontology analysis revealed that both treatments altered the expression of key functional genes involved in major functions like phosphorylation mechanisms, transmembrane transport and oxidoreduction activities. Interestingly, even though no host plant tissue was present in the in vitro system, PCA also led to the overexpression of several genes encoding effectors. The mutant only slightly repressed P. infestans' growth and barely altered its transcriptome.

CONCLUSIONS: Our study suggests that PCA is involved in P. infestans' growth repression and led to important transcriptomic changes by both up- and down-regulating gene expression in P. infestans over time. Different metabolic functions were altered and many effectors were found to be upregulated, suggesting their implication in biocontrol.}, } @article {pmid29914351, year = {2018}, author = {Quentin, Y and Siguier, P and Chandler, M and Fichant, G}, title = {Single-strand DNA processing: phylogenomics and sequence diversity of a superfamily of potential prokaryotic HuH endonucleases.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {475}, pmid = {29914351}, issn = {1471-2164}, support = {ANR‑12‑BSV8‑0009‑01//Agence Nationale de la Recherche/ ; }, mesh = {Amino Acid Motifs ; Archaeal Proteins/chemistry/*classification/genetics ; Bacterial Proteins/chemistry/*classification/genetics ; DNA, Single-Stranded/metabolism ; Endodeoxyribonucleases/chemistry/*classification/genetics ; Genetic Variation ; Inverted Repeat Sequences ; Multigene Family ; Phylogeny ; Protein Domains ; Transposases/chemistry/*classification/genetics ; }, abstract = {BACKGROUND: Some mobile genetic elements target the lagging strand template during DNA replication. Bacterial examples are insertion sequences IS608 and ISDra2 (IS200/IS605 family members). They use obligatory single-stranded circular DNA intermediates for excision and insertion and encode a transposase, TnpAIS200, which recognizes subterminal secondary structures at the insertion sequence ends. Similar secondary structures, Repeated Extragenic Palindromes (REP), are present in many bacterial genomes. TnpAIS200-related proteins, TnpAREP, have been identified and could be responsible for REP sequence proliferation. These proteins share a conserved HuH/Tyrosine core domain responsible for catalysis and are involved in processes of ssDNA cleavage and ligation. Our goal is to characterize the diversity of these proteins collectively referred as the TnpAY1 family.

RESULTS: A genome-wide analysis of sequences similar to TnpAIS200 and TnpAREP in prokaryotes revealed a large number of family members with a wide taxonomic distribution. These can be arranged into three distinct classes and 12 subclasses based on sequence similarity. One subclass includes sequences similar to TnpAIS200. Proteins from other subclasses are not associated with typical insertion sequence features. These are characterized by specific additional domains possibly involved in protein/DNA or protein/protein interactions. Their genes are found in more than 25% of species analyzed. They exhibit a patchy taxonomic distribution consistent with dissemination by horizontal gene transfers followed by loss. The tnpAREP genes of five subclasses are flanked by typical REP sequences in a REPtron-like arrangement. Four distinct REP types were characterized with a subclass specific distribution. Other subclasses are not associated with REP sequences but have a large conserved domain located in C-terminal end of their sequence. This unexpected diversity suggests that, while most likely involved in processing single-strand DNA, proteins from different subfamilies may play a number of different roles.

CONCLUSIONS: We established a detailed classification of TnpAY1 proteins, consolidated by the analysis of the conserved core domains and the characterization of additional domains. The data obtained illustrate the unexpected diversity of the TnpAY1 family and provide a strong framework for future evolutionary and functional studies. By their potential function in ssDNA editing, they may confer adaptive responses to host cell physiology and metabolism.}, } @article {pmid29914350, year = {2018}, author = {Chen, S and Mar, JC}, title = {Evaluating methods of inferring gene regulatory networks highlights their lack of performance for single cell gene expression data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {232}, pmid = {29914350}, issn = {1471-2105}, abstract = {BACKGROUND: A fundamental fact in biology states that genes do not operate in isolation, and yet, methods that infer regulatory networks for single cell gene expression data have been slow to emerge. With single cell sequencing methods now becoming accessible, general network inference algorithms that were initially developed for data collected from bulk samples may not be suitable for single cells. Meanwhile, although methods that are specific for single cell data are now emerging, whether they have improved performance over general methods is unknown. In this study, we evaluate the applicability of five general methods and three single cell methods for inferring gene regulatory networks from both experimental single cell gene expression data and in silico simulated data.

RESULTS: Standard evaluation metrics using ROC curves and Precision-Recall curves against reference sets sourced from the literature demonstrated that most of the methods performed poorly when they were applied to either experimental single cell data, or simulated single cell data, which demonstrates their lack of performance for this task. Using default settings, network methods were applied to the same datasets. Comparisons of the learned networks highlighted the uniqueness of some predicted edges for each method. The fact that different methods infer networks that vary substantially reflects the underlying mathematical rationale and assumptions that distinguish network methods from each other.

CONCLUSIONS: This study provides a comprehensive evaluation of network modeling algorithms applied to experimental single cell gene expression data and in silico simulated datasets where the network structure is known. Comparisons demonstrate that most of these assessed network methods are not able to predict network structures from single cell expression data accurately, even if they are specifically developed for single cell methods. Also, single cell methods, which usually depend on more elaborative algorithms, in general have less similarity to each other in the sets of edges detected. The results from this study emphasize the importance for developing more accurate optimized network modeling methods that are compatible for single cell data. Newly-developed single cell methods may uniquely capture particular features of potential gene-gene relationships, and caution should be taken when we interpret these results.}, } @article {pmid29914348, year = {2018}, author = {Zhang, W and Yue, X and Lin, W and Wu, W and Liu, R and Huang, F and Liu, F}, title = {Predicting drug-disease associations by using similarity constrained matrix factorization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {233}, pmid = {29914348}, issn = {1471-2105}, abstract = {BACKGROUND: Drug-disease associations provide important information for the drug discovery. Wet experiments that identify drug-disease associations are time-consuming and expensive. However, many drug-disease associations are still unobserved or unknown. The development of computational methods for predicting unobserved drug-disease associations is an important and urgent task.

RESULTS: In this paper, we proposed a similarity constrained matrix factorization method for the drug-disease association prediction (SCMFDD), which makes use of known drug-disease associations, drug features and disease semantic information. SCMFDD projects the drug-disease association relationship into two low-rank spaces, which uncover latent features for drugs and diseases, and then introduces drug feature-based similarities and disease semantic similarity as constraints for drugs and diseases in low-rank spaces. Different from the classic matrix factorization technique, SCMFDD takes the biological context of the problem into account. In computational experiments, the proposed method can produce high-accuracy performances on benchmark datasets, and outperform existing state-of-the-art prediction methods when evaluated by five-fold cross validation and independent testing.

CONCLUSION: We developed a user-friendly web server by using known associations collected from the CTD database, available at http://www.bioinfotech.cn/SCMFDD/ . The case studies show that the server can find out novel associations, which are not included in the CTD database.}, } @article {pmid29913458, year = {2018}, author = {Rovatsos, M and Augstenová, B and Altmanová, M and Sloboda, M and Kodym, P and Kratochvíl, L}, title = {Triploid Colubrid Snake Provides Insight into the Mechanism of Sex Determination in Advanced Snakes.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000490124}, pmid = {29913458}, issn = {1661-5433}, abstract = {The advanced snakes (Caenophidia), the important amniote lineage encompassing more than 3,000 living species, possess highly conserved female heterogamety across all families. However, we still lack any knowledge on the gene(s) and the molecular mechanism controlling sex determination. Triploid individuals spontaneously appear in populations of diploid species and can provide an important insight into the evolution of sex determination. Here, we report a case of spontaneous triploidy in a male of the twin-spotted ratsnake (Elaphe bimaculata) with ZZW sex chromosomes. We speculate that as both ZZ and ZZW individuals develop male gonads, the ratio between the number of Z chromosomes and autosomes, and not the presence of the W chromosome in the genome, drives sex determination in the advanced snakes.}, } @article {pmid29913312, year = {2018}, author = {Lagourgue, L and Puillandre, N and Payri, CE}, title = {Exploring the Udoteaceae diversity (Bryopsidales, Chlorophyta) in the Caribbean region based on molecular and morphological data.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {758-769}, doi = {10.1016/j.ympev.2018.06.023}, pmid = {29913312}, issn = {1095-9513}, abstract = {The Udoteaceae family (Bryopsidales, Chlorophyta) is known to be highly diverse morphologically in the Caribbean region, but only few studies have studied its genetic diversity. Using an integrative taxonomic approach, this study aimed at (1) exploring the Udoteaceae species diversity using a combination of five DNA-based species delimitation methods and morpho-anatomical data for confirmation; (2) estimating the discriminatory power of traditional diagnostic characters using a morphology-based clustering method and statistical analyses focused on the genus Udotea; and (3) reconstructing the phylogeny of the family based on a multilocus analysis (tufA, rbcL, 18S rDNA). Our results revealed strong congruence between species hypotheses across delimitation methods and markers. Morpho-anatomical characters proved essential to validate these hypotheses, to assign species names and to unveil new species. Morphological analyses led to relevant results for accurately discriminating Udotea morphospecies. Siphon features and cortication were key characters to define supra-specific groups and to revise the taxonomy of the genus Udotea. Phylogenetic analyses confirmed the polyphyly of Udotea, Rhipocephalus and Penicillus, which led us to propose a revised definition of Udotea sensu stricto based on both genetic and morphological data. Finally, our study emphasizes the importance of combining genetic and morphological data for the taxonomic revision of the Udoteaceae, but stresses the need of including more taxa from other geographical regions to better resolve taxonomic issues.}, } @article {pmid29913311, year = {2018}, author = {Schönhuth, S and Vukić, J and Šanda, R and Yang, L and Mayden, RL}, title = {Phylogenetic relationships and classification of the Holarctic family Leuciscidae (Cypriniformes: Cyprinoidei).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {781-799}, doi = {10.1016/j.ympev.2018.06.026}, pmid = {29913311}, issn = {1095-9513}, abstract = {The phylogenetic relationships and classification of the freshwater fish order Cypriniformes, like many other species-rich groups of vertebrates, has evolved over time with some consistency and inconsistencies of relationships across various studies. Within Cypriniformes, the Holarctic family Leuciscidae is one of the most widely distributed and highly diverse monophyletic groups of cyprinoids. Despite several studies conducted on this group, alternative hypotheses exist as to the composition and relationships within Leuciscidae. Here we assess the extent, composition, phylogenetic relationships, and taxonomy of this highly diverse group of fishes, using multiple mitochondrial and nuclear loci and a comprehensive and dense taxonomic sampling. Analyses of 418 specimens (410 species) resolve a well-supported Leuciscidae including 362 specimens (358 taxa) in six well-supported subfamilies/major clades: Pseudaspininae/Far East Asian clade (FEA); Laviniinae/North American Western clade (WC); Plagopterinae/North American Creek Chub-Plagopterin clade (CC-P); Leuciscinae/Eurasian Old World clade (OW) (minus Phoxinus) plus North American Notemigonus; Phoxininae/Eurasian Phoxinus clade (PHX); and Pogonichthyinae/North American clade (NA) including all remaining leuciscids. Within Leuciscidae, neither the traditional phoxinins (Phoxinus, FEA, Nearctic genera) nor all Nearctic genera (minus Notemigonus) are resolved as monophyletic; whereas the WC and CC-P form two independent lineages from remaining North American cyprinoids. A close relationship exists between Eurasian Phoxinus, NA, and OW clades, while FEA is the sister group to all remaining Leuciscidae. Major lineages resolved within these six subfamilies are mostly congruent with some previous studies. Our results suggests a complex evolutionary history of this diverse and widespread group of fishes.}, } @article {pmid29913310, year = {2018}, author = {Vaux, F and Trewick, SA and Crampton, JS and Marshall, BA and Beu, AG and Hills, SFK and Morgan-Richards, M}, title = {Evolutionary lineages of marine snails identified using molecular phylogenetics and geometric morphometric analysis of shells.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {626-637}, doi = {10.1016/j.ympev.2018.06.009}, pmid = {29913310}, issn = {1095-9513}, abstract = {The relationship between morphology and inheritance is of perennial interest in evolutionary biology and palaeontology. Using three marine snail genera Penion, Antarctoneptunea and Kelletia, we investigate whether systematics based on shell morphology accurately reflect evolutionary lineages indicated by molecular phylogenetics. Members of these gastropod genera have been a taxonomic challenge due to substantial variation in shell morphology, conservative radular and soft tissue morphology, few known ecological differences, and geographical overlap between numerous species. Sampling all sixteen putative taxa identified across the three genera, we infer mitochondrial and nuclear ribosomal DNA phylogenetic relationships within the group, and compare this to variation in adult shell shape and size. Results of phylogenetic analysis indicate that each genus is monophyletic, although the status of some phylogenetically derived and likely more recently evolved taxa within Penion is uncertain. The recently described species P. lineatus is supported by genetic evidence. Morphology, captured using geometric morphometric analysis, distinguishes the genera and matches the molecular phylogeny, although using the same dataset, species and phylogenetic subclades are not identified with high accuracy. Overall, despite abundant variation, we find that shell morphology accurately reflects genus-level classification and the corresponding deep phylogenetic splits identified in this group of marine snails.}, } @article {pmid29912397, year = {2018}, author = {Bolourian, A and Mojtahedi, Z}, title = {Streptomyces, shared microbiome member of soil and gut, as 'old friends' against colon cancer.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy120}, pmid = {29912397}, issn = {1574-6941}, abstract = {Inflammation contributes to colon cancer initiation. The disease along with allergy and autoimmunity has been on the rise in Western and more recently in developing countries. This shared rise may imply a shared cause. Streptomycetes are known as soil residents and produce numerous antiproliferative, anti-inflammatory/immunosuppressive compounds, e.g. rapamycin and tacrolimus. Recently, Streptomyces has been shown in gut microbiome with a lower prevalence in humans than nonhumans whose microbiomes might be more representative of past humans' in a hunter-gatherer and farming environment. It was previously suggested that Streptomyces producing antiproliferatives/immunosuppressants would be 'old friends' against allergy and autoimmunity as well as inflammatory bowel diseases. Here, it is suggested that these streptomycetes within gut microbiome have also been evolved as 'old friends' to suppress colon tumorigenesis through their numerous antiproliferatives/immunosuppressants. Subsequently, the shortage of exposure to nature in our current lifestyle has cost us the shortage of these friends and vulnerability to colon cancer. An attractive research area in the future would be whether the shortage of Streptomyces exposure can be the underlying reason for colon cancer, allergy and autoimmunity rise, and if the restoration of these 'old friends' through probiotics or more exposure to nature can prevent colon cancer.}, } @article {pmid29912330, year = {2018}, author = {Pohlschroder, M and Pfeiffer, F and Schulze, S and Halim, MFA}, title = {Archaeal cell surface biogenesis.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {694-717}, pmid = {29912330}, issn = {1574-6976}, mesh = {Archaea/*metabolism ; Archaeal Proteins/*biosynthesis/metabolism ; Membrane Proteins/*biosynthesis/metabolism ; *Protein Processing, Post-Translational ; }, abstract = {Cell surfaces are critical for diverse functions across all domains of life, from cell-cell communication and nutrient uptake to cell stability and surface attachment. While certain aspects of the mechanisms supporting the biosynthesis of the archaeal cell surface are unique, likely due to important differences in cell surface compositions between domains, others are shared with bacteria or eukaryotes or both. Based on recent studies completed on a phylogenetically diverse array of archaea, from a wide variety of habitats, here we discuss advances in the characterization of mechanisms underpinning archaeal cell surface biogenesis. These include those facilitating co- and post-translational protein targeting to the cell surface, transport into and across the archaeal lipid membrane, and protein anchoring strategies. We also discuss, in some detail, the assembly of specific cell surface structures, such as the archaeal S-layer and the type IV pili. We will highlight the importance of post-translational protein modifications, such as lipid attachment and glycosylation, in the biosynthesis as well as the regulation of the functions of these cell surface structures and present the differences and similarities in the biogenesis of type IV pili across prokaryotic domains.}, } @article {pmid29912327, year = {2018}, author = {Osterholz, H and Kirchman, DL and Niggemann, J and Dittmar, T}, title = {Diversity of bacterial communities and dissolved organic matter in a temperate estuary.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy119}, pmid = {29912327}, issn = {1574-6941}, abstract = {Relationships between bacterial community and dissolved organic matter (DOM) include microbial uptake, transformation and secretion, all of which influence DOM composition. In this study, we explore diversity and similarity metrics of dissolved organic molecules (Fourier-transform ion cyclotron resonance mass spectrometry) and bacterial communities (tag-sequencing of 16S rRNA genes) along the salinity gradient of the Delaware Estuary (USA). We found that even though mixing, discharge and seasonal changes explained most of the variation in DOM and bacterial communities, there was still a relationship, albeit weak, between the composition of DOM and bacterial communities in the estuary. Overall, many DOM molecular formulas (MFs) and bacterial operational taxonomic units (OTUs) reoccurred over years and seasons, while the frequency of MF-OTU correlations varied. Diversity based on MFs and OTUs was significantly correlated, decreasing towards the open ocean. However, while the diversity of bacterial OTUs dropped markedly with low salinity, MF diversity decreased strongly only at high salinities. We hypothesize that the different turnover times of DOM and bacteria lead to different abundance distributions of OTUs and MFs. A significant portion of the detected DOM is of a more refractory nature with lifetimes largely exceeding the mixing time of the estuary, while bacterial community turnover times in the Delaware Estuary are estimated at several days.}, } @article {pmid29912326, year = {2018}, author = {Ruiz-González, C and Archambault, E and Laforest-Lapointe, I and Del Giorgio, PA and Kembel, SW and Messier, C and Nock, CA and Beisner, BE}, title = {Soils associated to different tree communities do not elicit predictable responses in lake bacterial community structure and function.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy115}, pmid = {29912326}, issn = {1574-6941}, abstract = {Freshwater bacterioplankton communities are influenced by the inputs of material and bacteria from the surrounding landscape, yet few studies have investigated how different terrestrial inputs affect bacterioplankton. We examined whether the addition of soils collected under various tree species combinations differentially influences lake bacterial communities. Lake water was incubated for 6 days following addition of five different soils. We assessed the taxonomic composition (16S rRNA gene sequencing) and metabolic activity (Biolog Ecoplates) of lake bacteria with and without soil addition, and compared these to initial soil communities. Soil bacterial assemblages showed a strong influence of tree composition, but such community differences were not reflected in the structure of lake communities that developed during the experiment. Bacterial taxa showing the largest abundance increases during incubation were initially present in both lake water and across most soils, and were related to Cytophagales, Burkholderiales and Rhizobiales. No clear metabolic profiles based on inoculum source were found, yet soil-amended communities used 60% more substrate than non-inoculated communities. Overall, we show that terrestrial inputs influence aquatic communities by stimulating the growth and activity of certain ubiquitous taxa distributed across the terrestrial-aquatic continuum, yet different forest soils did not cause predictable changes in lake bacterioplankton assemblages.}, } @article {pmid29912319, year = {2018}, author = {Maggini, V and Miceli, E and Fagorzi, C and Maida, I and Fondi, M and Perrin, E and Mengoni, A and Bogani, P and Chiellini, C and Mocali, S and Fabiani, A and Decorosi, F and Giovannetti, L and Firenzuoli, F and Fani, R}, title = {Antagonism and antibiotic resistance drive a species-specific plant microbiota differentiation in Echinacea spp.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy118}, pmid = {29912319}, issn = {1574-6941}, abstract = {A key factor in the study of plant-microbes interactions is the composition of plant microbiota, but little is known about the factors determining its functional and taxonomic organization. Here we investigated the possible forces driving the assemblage of bacterial endophytic and rhizospheric communities, isolated from two congeneric medicinal plants, Echinacea purpurea (L.) Moench and Echinacea angustifolia (DC) Heller, grown in the same soil, by analysing bacterial strains (isolated from three different compartments, i.e. rhizospheric soil, roots and stem/leaves) for phenotypic features such as antibiotic resistance, extracellular enzymatic activity, siderophore and indole 3-acetic acid production, as well as cross-antagonistic activities. Data obtained highlighted that bacteria from different plant compartments were characterized by specific antibiotic resistance phenotypes and antibiotic production, suggesting that the bacterial communities themselves could be responsible for structuring their own communities by the production of antimicrobial molecules selecting bacterial-adaptive phenotypes for plant tissue colonization.}, } @article {pmid29912311, year = {2018}, author = {Bottos, EM and Kennedy, DW and Romero, EB and Fansler, SJ and Brown, JM and Bramer, LM and Chu, RK and Tfaily, MM and Jansson, JK and Stegen, JC}, title = {Dispersal limitation and thermodynamic constraints govern spatial structure of permafrost microbial communities.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy110}, pmid = {29912311}, issn = {1574-6941}, abstract = {Understanding drivers of permafrost microbial community composition is critical for understanding permafrost microbiology and predicting ecosystem responses to thaw. We hypothesize that permafrost communities are shaped by physical constraints imposed by prolonged freezing, and exhibit spatial distributions that reflect dispersal limitation and selective pressures associated with these physical constraints. To test this, we characterized patterns of environmental variation and microbial community composition in permafrost across an Alaskan boreal forest landscape. We used null modeling to estimate the importance of selective and neutral assembly processes on community composition, and identified environmental factors influencing ecological selection through regression and structural equation modeling (SEM). Proportionally, the strongest process influencing community composition was dispersal limitation (0.36), exceeding the influence of homogenous selection (0.21), variable selection (0.16) and homogenizing dispersal (0.05). Fe(II) content was the most important factor explaining variable selection, and was significantly associated with total selection by univariate regression (R2 = 0.14, P = 0.003). SEM supported a model in which Fe(II) content mediated influences of the Gibbs free energy of the organic matter pool and organic acid concentration on total selection. These findings suggest that the dominant processes shaping microbial communities in permafrost result from the stability of the permafrost environment, which imposes dispersal and thermodynamic constraints.}, } @article {pmid29912309, year = {2018}, author = {Zatopek, KM and Gardner, AF and Kelman, Z}, title = {Archaeal DNA replication and repair: new genetic, biophysical and molecular tools for discovering and characterizing enzymes, pathways and mechanisms.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {477-488}, doi = {10.1093/femsre/fuy017}, pmid = {29912309}, issn = {1574-6976}, mesh = {Archaea/genetics/*physiology ; Archaeal Proteins/metabolism ; *DNA Repair ; DNA Replication/*genetics ; DNA, Archaeal/*genetics ; }, abstract = {DNA replication and repair are essential biological processes needed for the survival of all organisms. Although these processes are fundamentally conserved in the three domains, archaea, bacteria and eukarya, the proteins and complexes involved differ. The genetic and biophysical tools developed for archaea in the last several years have accelerated the study of DNA replication and repair in this domain. In this review, the current knowledge of DNA replication and repair processes in archaea will be summarized, with emphasis on the contribution of genetics and other recently developed biophysical and molecular tools, including capillary gel electrophoresis, next-generation sequencing and single-molecule approaches. How these new tools will continue to drive archaeal DNA replication and repair research will also be discussed.}, } @article {pmid29911426, year = {2018}, author = {Eldakar, OT and Kammeyer, JO and Nagabandi, N and Gallup, AC}, title = {Hypocrisy and Corruption: How Disparities in Power Shape the Evolution of Social Control.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918756993}, doi = {10.1177/1474704918756993}, pmid = {29911426}, issn = {1474-7049}, mesh = {*Altruism ; *Biological Evolution ; *Game Theory ; *Group Processes ; Humans ; Models, Psychological ; *Power (Psychology) ; Punishment/*psychology ; *Social Control, Formal ; }, abstract = {Altruism presents an evolutionary paradox, as altruistic individuals are good for the group yet vulnerable to exploitation by selfish individuals. One mechanism that can effectively curtail selfishness within groups is punishment. Here, we show in an evolutionary game-theoretical model that punishment can effectively evolve and maintain high levels of altruism in the population, yet not all punishment strategies were equally virtuous. Unlike typical models of social evolution, we explicitly altered the extent to which individuals vary in their power over others, such that powerful individuals can more readily punish and escape the punishment of others. Two primary findings emerged. Under large power asymmetries, a powerful selfish minority maintained altruism of the masses. In contrast, increased symmetry of power among individuals produced a more egalitarian society held together by altruism and punishment carried out by the collective. These extremes are consistent with the coercive nature of the powerful elites in social insects and egalitarian mechanisms of punishment in humans such as coalitional enforcement and gossip. Our overall findings provide insights into the importance of oversight, the consequences to changes in the power structure of social systems, and the roots of hypocrisy and corruption in human and nonhuman animal societies.}, } @article {pmid29911423, year = {2018}, author = {Grabo, A and van Vugt, M}, title = {Voting for a Male Warrior or Female Peacekeeper? Testing the Evolutionary Contingency Hypothesis in the 2016 U.S. Presidential Elections.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918773267}, doi = {10.1177/1474704918773267}, pmid = {29911423}, issn = {1474-7049}, mesh = {Adult ; *Biological Evolution ; Female ; *Femininity ; *Group Processes ; Humans ; *Leadership ; Male ; *Masculinity ; *Personality ; *Politics ; *Social Perception ; }, abstract = {The present research replicates and extends previous literature on the evolutionary contingency hypothesis of leadership emergence. Using artificially masculinized versus feminized versions of the faces of the candidates for the 2016 U.S. presidential elections, we demonstrated that different contextual cues produced systematic variation in both preferences for and personality impressions of leadership. We describe results of an online study (N = 298), demonstrating that followers who perceived a match between the contextual prime (intergroup conflict or cooperation) and a leader candidate's relevant physical cues (masculinized or feminized versions of their faces) both (a) preferred them as leaders and (b) rated them more positively on personality attributes commonly associated with effective leadership such as trustworthiness, warmth, competence, and charisma.}, } @article {pmid29911420, year = {2018}, author = {McDermott, R and Hatemi, PK}, title = {To Go Forward, We Must Look Back: The Importance of Evolutionary Psychology for Understanding Modern Politics.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918764506}, doi = {10.1177/1474704918764506}, pmid = {29911420}, issn = {1474-7049}, mesh = {*Biological Evolution ; Humans ; *Politics ; *Psychology/trends ; }, abstract = {As new waves of populism arise and cause disruption around the globe, there is both great interest in attempting to explain the origin of this dynamic as well as a need to ameliorate its potentially destructive impact. Perhaps the greatest signal of seismic change is the global dismantling of American institutional control of the postwar world following the election of Donald Trump in the United States. In the wake of such dramatic changes, it may seem odd to turn to evolutionary psychology which looks deeply into the past to try to understand current events, but, in fact, modern technology has dramatically changed the shape of political communication in just such a way as to make politics more personal once again, increasing the need to understand and interpret modern politics through an evolutionary lens. In fact, current modern political turmoils demonstrate how important evolutionary themes are and how critical they remain to understand how current forms of populism tape into older tribal sentiments and drives. Modern technology allows for a form of interpretative politics that no longer need to be mediated by political institutions or larger social structures, including enduring ones such as marriage. Indeed, in any ways, as we have technologically advanced, we have also regressed to more immediate, emotional, and personal forms of political communication. And it is only in understanding the nature of that personal political psychology that we can begin to grapple seriously with the challenges of today, including the consequences of global populism.}, } @article {pmid29911419, year = {2018}, author = {Billingsley, J and Lieberman, D and Tybur, JM}, title = {Sexual Disgust Trumps Pathogen Disgust in Predicting Voter Behavior During the 2016 U.S. Presidential Election.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918764170}, doi = {10.1177/1474704918764170}, pmid = {29911419}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Communicable Diseases/*psychology ; *Emotions ; Female ; Humans ; Male ; Middle Aged ; *Morals ; *Politics ; Sexual Behavior/*psychology ; *Social Behavior ; United States ; Young Adult ; }, abstract = {Why is disgust sensitivity associated with socially conservative political views? Is it because socially conservative ideologies mitigate the risks of infectious disease, whether by promoting out-group avoidance or by reinforcing norms that sustain antipathogenic practices? Or might it be because socially conservative ideologies promote moral standards that advance a long-term, as opposed to a short-term, sexual strategy? Recent attempts to test these two explanations have yielded differing results and conflicting interpretations. Here, we contribute to the literature by examining the relationship between disgust sensitivity and political orientation, political party affiliation, and an often overlooked outcome-actual voter behavior. We focus on voter behavior and affiliation for the 2016 U.S. presidential election to determine whether pathogen or sexual disgust better predicts socially conservative ideology. Although many prominent aspects of Donald Trump's campaign-particularly his anti-foreign message-align with the pathogen-avoidance model of conservatism, we found that pathogen-related disgust sensitivity exerted no influence on political ideology, political party affiliation, or voter behavior, after controlling for sexual disgust sensitivity. In contrast, sexual disgust sensitivity was associated with increased odds of voting for Donald Trump versus each other major presidential candidate, as well as with increased odds of affiliating with the Republican versus the Democratic or Libertarian parties. In fact, for every unit increase in sexual disgust sensitivity, the odds of a participant voting for Trump versus Clinton increased by approximately 30%. It seems, then, that sexual disgust trumps pathogen disgust in predicting socially conservative voting behavior.}, } @article {pmid29911417, year = {2018}, author = {Lindner, M}, title = {Public Reactions to Male Versus Female Terrorism: Experimental Evidence for the Male Warrior Hypothesis.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918764578}, doi = {10.1177/1474704918764578}, pmid = {29911417}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Aged ; *Attitude ; *Conflict (Psychology) ; Female ; *Group Processes ; Humans ; Male ; Middle Aged ; Sex Factors ; *Social Perception ; Terrorism/*psychology ; Young Adult ; }, abstract = {One of the most consistent findings in the domain of criminal justice is that female and male offenders are perceived differently, often resulting in milder sentencing of women compared to men. Although previous studies have sought to identify factors that shape public reactions to terrorism and support for harsh interrogation techniques in its aftermath, empirical studies on differential reactions to female (vs. male) terrorist violence remain scarce. Here, it is argued that the often-violent evolutionary history of our species has shaped the way in which we perceive and react to female (vs. male) terrorist violence. Based on the framework of coalitional psychology-and specifically, the male warrior hypothesis-the assumption is tested that terror-suspect sex, in interaction with other threat cues such as in- or out-group membership and size of coalition, affects support for interrogational torture. This prediction was tested by conducting a survey experiment on a nationally representative sample of 2,126 U.S. adults. Results demonstrated that terror-suspect sex significantly shapes reactions to and perceptions of terrorist violence. Further, nuanced responses based on respondent sex revealed that these associations were exclusively driven by male participants. Gender attitudes and mere punitiveness did not account for the findings, suggesting that male coalitional psychology is deeply ingrained and readily activated by cues implying intergroup conflict.}, } @article {pmid29911407, year = {2018}, author = {Laustsen, L and Petersen, MB}, title = {When the Party Decides: The Effects of Facial Competence and Dominance on Internal Nominations of Political Candidates.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704917732005}, doi = {10.1177/1474704917732005}, pmid = {29911407}, issn = {1474-7049}, mesh = {Adult ; Denmark ; Facial Recognition/*physiology ; Female ; Humans ; *Local Government ; Male ; *Politics ; *Social Dominance ; *Social Perception ; }, abstract = {The facial traits and appearance of political candidates have been found to predict election outcomes across countries with different electoral systems and institutions. Research over the last decade has provided two different versions of this overall conclusion. First and most thoroughly studied, candidates who from their mere faces are evaluated as more competent get more votes on Election Day. Second, recent research finds that the ideological leanings of candidates and the voters they cater to also matter: Right-wing and conservative candidates receive more votes if they look more dominant, while liberal candidates lose votes when looking dominant and masculine. In this article, we investigate whether these patterns extend to candidate selection and support within parties as determined by party organizations. We test this through an original combination of naive respondents' trait ratings of candidates in Danish local elections and these candidates' positions on the ballot as decided by nomination processes within local party organizations. The results strongly support that the conclusions in previous studies extend to dynamics within the party among party members: Danish local party organizations tend to nominate facially competent candidates at the top of the ballot regardless of their ideological leaning. Moreover, liberal and conservative parties position dominant-looking candidates significantly different on the ballot with liberal parties being less likely to assign facially dominant candidates to top ballot positions. These results add important new insights about the underlying psychological processes causing appearance-based voting and relate to the ongoing discussion about the quality of public opinion formation.}, } @article {pmid29911406, year = {2018}, author = {Jost, JT and Sapolsky, RM and Nam, HH}, title = {Speculations on the Evolutionary Origins of System Justification.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918765342}, doi = {10.1177/1474704918765342}, pmid = {29911406}, issn = {1474-7049}, mesh = {Amygdala/*physiology ; Animals ; *Biological Evolution ; Gyrus Cinguli/*physiology ; *Hierarchy, Social ; Humans ; *Politics ; *Social Behavior ; *Social Change ; *Social Dominance ; }, abstract = {For centuries, philosophers and social theorists have wondered why people submit voluntarily to tyrannical leaders and oppressive regimes. In this article, we speculate on the evolutionary origins of system justification, that is, the ways in which people are motivated (often nonconsciously) to defend and justify existing social, economic, and political systems. After briefly recounting the logic of system justification theory and some of the most pertinent empirical evidence, we consider parallels between the social behaviors of humans and other animals concerning the acceptance versus rejection of hierarchy and dominance. Next, we summarize research in human neuroscience suggesting that specific brain regions, such as the amygdala and the anterior cingulate cortex, may be linked to individual differences in ideological preferences concerning (in)equality and social stability as well as the successful navigation of complex, hierarchical social systems. Finally, we consider some of the implications of a system justification perspective for the study of evolutionary psychology, political behavior, and social change.}, } @article {pmid29911405, year = {2018}, author = {Banai, B and Laustsen, L and Banai, IP and Bovan, K}, title = {Presidential, But Not Prime Minister, Candidates With Lower Pitched Voices Stand a Better Chance of Winning the Election in Conservative Countries.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918758736}, doi = {10.1177/1474704918758736}, pmid = {29911405}, issn = {1474-7049}, mesh = {*Government ; Humans ; *Masculinity ; *Politics ; *Voice ; }, abstract = {Previous studies have shown that voters rely on sexually dimorphic traits that signal masculinity and dominance when they choose political leaders. For example, voters exert strong preferences for candidates with lower pitched voices because these candidates are perceived as stronger and more competent. Moreover, experimental studies demonstrate that conservative voters, more than liberals, prefer political candidates with traits that signal dominance, probably because conservatives are more likely to perceive the world as a threatening place and to be more attentive to dangerous and threatening contexts. In light of these findings, this study investigates whether country-level ideology influences the relationship between candidate voice pitch and electoral outcomes of real elections. Specifically, we collected voice pitch data for presidential and prime minister candidates, aggregate national ideology for the countries in which the candidates were nominated, and measures of electoral outcomes for 69 elections held across the world. In line with previous studies, we found that candidates with lower pitched voices received more votes and had greater likelihood of winning the elections. Furthermore, regression analysis revealed an interaction between candidate voice pitch, national ideology, and election type (presidential or parliamentary). That is, having a lower pitched voice was a particularly valuable asset for presidential candidates in conservative and right-leaning countries (in comparison to presidential candidates in liberal and left-leaning countries and parliamentary elections). We discuss the practical implications of these findings, and how they relate to existing research on candidates' voices, voting preferences, and democratic elections in general.}, } @article {pmid29911337, year = {2018}, author = {Schäfer, MA and Berger, D and Rohner, PT and Kjaersgaard, A and Bauerfeind, SS and Guillaume, F and Fox, CW and Blanckenhorn, WU}, title = {Geographic clines in wing morphology relate to colonization history in New World but not Old World populations of yellow dung flies.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13517}, pmid = {29911337}, issn = {1558-5646}, abstract = {Geographic clines offer insights about putative targets and agents of natural selection as well as tempo and mode of adaptation. However, demographic processes can lead to clines that are indistinguishable from adaptive divergence. Using the widespread yellow dung fly Scathophaga stercoraria (Diptera: Scathophagidae), we examine quantitative genetic differentiation (QST) of wing shape across North America, Europe, and Japan, and compare this differentiation with that of ten microsatellites (FST). Morphometric analyses of 28 populations reared at three temperatures revealed significant thermal plasticity, sexual dimorphism, and geographic differentiation in wing shape. In North America morphological differentiation followed the decline in microsatellite variability along the presumed route of recent colonization from the southeast to the northwest. Across Europe, where S. stercoraria presumably existed for much longer time and where no molecular pattern of isolation by distance was evident, clinal variation was less pronounced despite significant morphological differentiation (QST >FST). Shape vector comparisons further indicate that thermal plasticity (hot-to-cold) does not mirror patterns of latitudinal divergence (south-to-north), as might have been expected under a scenario with temperature as the major agent of selection. Our findings illustrate the importance of detailed phylogeographic information when interpreting geographic clines of dispersal traits in an adaptive evolutionary framework.}, } @article {pmid29910182, year = {2018}, author = {Laurance, WF}, title = {Conservation and the Global Infrastructure Tsunami: Disclose, Debate, Delay!.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {568-571}, doi = {10.1016/j.tree.2018.05.007}, pmid = {29910182}, issn = {1872-8383}, abstract = {Efforts to protect nature are facing a growing crisis, one that often revolves around the burgeoning impacts of roads and other infrastructure on biodiversity and ecosystems. Potential solutions are possible but they will involve serious trade-offs and the confrontation of deep misconceptions. Here, I identify some time-critical tactics to aid scientists in informing and influencing the global infrastructure debate.}, } @article {pmid29910092, year = {2018}, author = {Erben, ED and Clayton, C}, title = {Codon Usage in Trypanosomatids: The Bias of Expression.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {635-637}, doi = {10.1016/j.pt.2018.06.001}, pmid = {29910092}, issn = {1471-5007}, mesh = {*Codon ; Protein Biosynthesis ; *RNA Stability ; RNA, Messenger ; }, abstract = {Translation and RNA decay, two processes in which all mRNAs are engaged, are intimately related processes. Two new studies demonstrate that, in trypanosomatids, codon usage largely shapes mRNA abundance in a translation-dependent manner. The findings indicate that mRNA decay control by codon choice is an ancient and conserved mechanism.}, } @article {pmid29910044, year = {2018}, author = {Grabowski, M and Hatala, KG and Jungers, WL}, title = {Body mass estimates of the earliest possible hominins and implications for the last common ancestor.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {84-92}, doi = {10.1016/j.jhevol.2018.05.001}, pmid = {29910044}, issn = {1095-8606}, abstract = {Many hypotheses regarding the paleobiology of the earliest possible hominins, Orrorin tugenensis and Ardipithecus ramidus, are dependent upon accurate body mass estimates for these taxa. While we have previously published body mass predictions for Orrorin and Ardipithecus, the accuracies of those estimates depend on the assumption that the postcranial skeletal dimensions and body masses of these taxa followed scaling patterns that were similar to those observed in modern humans. This assumption may not be correct because certain aspects of postcranial morphology in Orrorin and Ardipithecus differ from modern humans, and suggest that their overall body plans might be unique but more similar to modern non-human great apes than to modern humans. Here we present individual body mass predictions for O. tugenensis and Ar. ramidus assuming that they followed postcranial scaling patterns similar to those of chimpanzees. All estimates include individual prediction intervals as measures of uncertainty. In addition, we provide equations for predicting body mass from univariate postcranial measurements based on the largest sample (n = 25) yet compiled of common chimpanzee skeletons with known body masses, which is vital for calculating prediction intervals for individual fossils. Our results show that estimated body masses in Orrorin and Ardipithecus are generally larger when derived from a chimpanzee-like scaling pattern compared to estimates that assume a human-like pattern, though the prediction intervals of the two sets of estimates overlap. In addition, the more complete of the two known Orrorin femora has an overall scaling pattern that is more similar to common chimpanzees than to modern humans, supporting the application of a non-human great ape comparative model. Our new estimates fall near the male (Ardipithecus) average and in between the male and female averages (Orrorin) for wild-caught common chimpanzees. If a chimpanzee-like pattern of scaling between postcranial dimensions and body mass did exist in these earliest hominins, our results suggest the large body masses found in some early australopiths were already present in taxa near the origins of our lineage, and perhaps also in the Pan-Homo last common ancestor.}, } @article {pmid29910043, year = {2018}, author = {Head, JJ and Müller, J}, title = {Squamate reptiles from Kanapoi: Faunal evidence for hominin paleoenvironments.}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2018.01.007}, pmid = {29910043}, issn = {1095-8606}, abstract = {The squamate fossil record from Kanapoi reveals generic to higher-order similarities with modern East African herpetofaunas. The record is derived from surface collection and screen washing, and consists primarily of isolated vertebrae with a few maxillary and mandibular elements. The most abundant remains are vertebrae of large-bodied Python that are morphologically similar to extant Python sebae, and vertebrae of Varanus cf. (Varanus niloticus + Varanus exanthematicus). Additional cranial and vertebral remains indicate the presence of lygosomine skinks, indeterminate Varanus, Viperidae, cf. Atractaspididae, and multiple colubrine morphotypes in the Kanapoi ecosystem. Despite similarities with modern herpetofaunas, the Kanapoi record lacks taxa common to other East African records, including agamids, chamaeleonids, amphisbaenians, the elapid Naja, and typhlopids. The overall composition of the Kanapoi squamate record is consistent with paleoenvironments similar to modern shrub savanna habitats. There are no indicators of canopied forest environments in squamate faunal composition. The fossil record of Kanapoi suggests that assembly of squamate faunas of modern East Africa was well underway by the late Neogene.}, } @article {pmid29909919, year = {2018}, author = {Scoma, A and Vorholt, JA}, title = {Editorial overview: Environmental microbiology: Environmental and engineered microbiomes.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {v-vii}, doi = {10.1016/j.mib.2018.05.004}, pmid = {29909919}, issn = {1879-0364}, } @article {pmid29909776, year = {2018}, author = {Yoshizawa, M and Settle, A and Hermosura, MC and Tuttle, LJ and Cetraro, N and Passow, CN and McGaugh, SE}, title = {The evolution of a series of behavioral traits is associated with autism-risk genes in cavefish.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {89}, pmid = {29909776}, issn = {1471-2148}, support = {16CON-78919//Hawaii Community Foundation/International ; }, mesh = {Animals ; Autistic Disorder/drug therapy/*genetics ; *Biological Evolution ; Caves ; Characidae/*genetics ; Crosses, Genetic ; Female ; Gene Expression Regulation ; *Genetic Predisposition to Disease ; Genome ; Humans ; Hybridization, Genetic ; Male ; Phenotype ; Quantitative Trait Loci/genetics ; *Quantitative Trait, Heritable ; Risk Factors ; }, abstract = {BACKGROUND: An essential question in evolutionary biology is whether shifts in a set of polygenic behaviors share a genetic basis across species. Such a behavioral shift is seen in the cave-dwelling Mexican tetra, Astyanax mexicanus. Relative to surface-dwelling conspecifics, cavefish do not school (asocial), are hyperactive and sleepless, adhere to a particular vibration stimulus (imbalanced attention), behave repetitively, and show elevated stress hormone levels. Interestingly, these traits largely overlap with the core symptoms of human autism spectrum disorder (ASD), raising the possibility that these behavioral traits are underpinned by a similar set of genes (i.e. a repeatedly used suite of genes).

RESULT: Here, we explored whether modification of ASD-risk genes underlies cavefish evolution. Transcriptomic analyses revealed that > 58.5% of 3152 cavefish orthologs to ASD-risk genes are significantly up- or down-regulated in the same direction as genes in postmortem brains from ASD patients. Enrichment tests suggest that ASD-risk gene orthologs in A. mexicanus have experienced more positive selection than other genes across the genome. Notably, these positively selected cavefish ASD-risk genes are enriched for pathways involved in gut function, inflammatory diseases, and lipid/energy metabolism, similar to symptoms that frequently coexist in ASD patients. Lastly, ASD drugs mitigated cavefish's ASD-like behaviors, implying shared aspects of neural processing.

CONCLUSION: Overall, our study indicates that ASD-risk genes and associated pathways (especially digestive, immune and metabolic pathways) may be repeatedly used for shifts in polygenic behaviors across evolutionary time.}, } @article {pmid29909175, year = {2018}, author = {Weissbrod, O and Rothschild, D and Barkan, E and Segal, E}, title = {Host genetics and microbiome associations through the lens of genome wide association studies.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {9-19}, doi = {10.1016/j.mib.2018.05.003}, pmid = {29909175}, issn = {1879-0364}, abstract = {Recent studies indicate that the gut microbiome is partially heritable, motivating the need to investigate microbiome-host genome associations via microbial genome-wide association studies (mGWAS). Existing mGWAS demonstrate that microbiome-host genotype associations are typically weak and are spread across multiple variants, similar to associations often observed in genome-wide association studies (GWAS) of complex traits. Here we reconsider mGWAS by viewing them through the lens of GWAS, and demonstrate that there are striking similarities between the challenges and pitfalls faced by the two study designs. We further advocate the mGWAS community to adopt three key lessons learned over the history of GWAS: firstly, adopting uniform data and reporting formats to facilitate replication and meta-analysis efforts; secondly, enforcing stringent statistical criteria to reduce the number of false positive findings; and thirdly, considering the microbiome and the host genome as distinct entities, rather than studying different taxa and single nucleotide polymorphism (SNPs) separately. Finally, we anticipate that mGWAS sample sizes will have to increase by orders of magnitude to reproducibly associate the host genome with the gut microbiome.}, } @article {pmid29909064, year = {2018}, author = {Frøland Steindal, IA and Beale, AD and Yamamoto, Y and Whitmore, D}, title = {Development of the Astyanax mexicanus circadian clock and non-visual light responses.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {345-354}, pmid = {29909064}, issn = {1095-564X}, support = {//Wellcome Trust/United Kingdom ; BB/D522346/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Characiformes/*physiology ; Circadian Clocks/*physiology ; Gene Expression Regulation/*physiology ; *Light ; Transcription, Genetic/*physiology ; }, abstract = {Most animals and plants live on the planet exposed to periods of rhythmic light and dark. As such, they have evolved endogenous circadian clocks to regulate their physiology rhythmically, and non-visual light detection mechanisms to set the clock to the environmental light-dark cycle. In the case of fish, circadian pacemakers are not only present in the majority of tissues and cells, but these tissues are themselves directly light-sensitive, expressing a wide range of opsin photopigments. This broad non-visual light sensitivity exists to set the clock, but also impacts a wide range of fundamental cell biological processes, such as DNA repair regulation. In this context, Astyanax mexicanus is a very intriguing model system with which to explore non-visual light detection and circadian clock function. Previous work has shown that surface fish possess the same directly light entrainable circadian clocks, described above. The same is true for cave strains of Astyanax in the laboratory, though no daily rhythms have been observed under natural dark conditions in Mexico. There are, however, clear alterations in the cave strain light response and changes to the circadian clock, with a difference in phase of peak gene expression and a reduction in amplitude. In this study, we expand these early observations by exploring the development of non-visual light sensitivity and clock function between surface and cave populations. When does the circadian pacemaker begin to oscillate during development, and are there differences between the various strains? Is the difference in acute light sensitivity, seen in adults, apparent from the earliest stages of development? Our results show that both cave and surface populations must experience daily light exposure to establish a larval gene expression rhythm. These oscillations begin early, around the third day of development in all strains, but gene expression rhythms show a significantly higher amplitude in surface fish larvae. In addition, the light induction of clock genes is developmentally delayed in cave populations. Zebrafish embryonic light sensitivity has been shown to be critical not only for clock entrainment, but also for transcriptional activation of DNA repair processes. Similar downstream transcriptional responses to light also occur in Astyanax. Interestingly, the establishment of the adult timing profile of clock gene expression takes several days to become apparent. This fact may provide mechanistic insight into the key differences between the cave and surface fish clock mechanisms.}, } @article {pmid29909044, year = {2018}, author = {Randall, G}, title = {Lipid Droplet Metabolism during Dengue Virus Infection.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {640-642}, doi = {10.1016/j.tim.2018.05.010}, pmid = {29909044}, issn = {1878-4380}, abstract = {Dengue virus (DENV) induces a proviral selective autophagy targeting lipid droplets, termed lipophagy, that stimulates lipid metabolism. Zhang et al. gained mechanistic insight into this process, demonstrating that DENV NS4A/B binds unmodified AUP1 and promotes its translocation from lipid droplets to autophagosomes to drive the induction of lipophagy.}, } @article {pmid29909043, year = {2018}, author = {Gow, NAR and Amin, T and McArdle, K and Brown, AJP and Brown, GD and Warris, A and The Wtsa-Mmfi Consortium, }, title = {Strategic Research Funding: A Success Story for Medical Mycology.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {811-813}, doi = {10.1016/j.tim.2018.05.014}, pmid = {29909043}, issn = {1878-4380}, abstract = {The Wellcome Trust Strategic Award in Medical Mycology and Fungal Immunology is a unique investment that aimed to bolster capacity, training and research activity throughout the UK. This article summarises the rationale for collective collaboration of multiple institutions to achieve synergies and address a common medical problem.}, } @article {pmid29909042, year = {2018}, author = {Keen, EC and Dantas, G}, title = {Close Encounters of Three Kinds: Bacteriophages, Commensal Bacteria, and Host Immunity.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {943-954}, doi = {10.1016/j.tim.2018.05.009}, pmid = {29909042}, issn = {1878-4380}, abstract = {Recent years have witnessed an explosion of interest in the human microbiota. Although commensal bacteria have dominated research efforts to date, mounting evidence suggests that endogenous viral populations (the 'virome') play key roles in basic human physiology. The most numerous constituents of the human virome are not eukaryotic viruses but rather bacteriophages, viruses that infect bacteria. Here, we review phages' interactions with their immediate (prokaryotic) and extended (eukaryotic) hosts and with each other, with a particular emphasis on the temperate phages and prophages which dominate the human virome. We also discuss key outstanding questions in this emerging field and emphasize the urgent need for functional studies in animal models to complement previous in vitro work and current computational approaches.}, } @article {pmid29909041, year = {2018}, author = {Hutchinson, EC}, title = {Influenza Virus.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {809-810}, doi = {10.1016/j.tim.2018.05.013}, pmid = {29909041}, issn = {1878-4380}, abstract = {This infographic briefly summarises the natural history, replication cycle, and pathogenesis of influenza viruses, the cause of seasonal influenza and of influenza pandemics. Influenza viruses infect many vertebrates, with Influenza A, B and C viruses (IAV, IBV, and ICV) infecting humans. High mutation rates allow the evasion of immunity. IAV from different host species can 'reassort' their segmented genomes, producing pandemic strains that are antigenically novel but otherwise well adapted to humans. The 'Great Influenza' pandemic of 1918 remains the worst outbreak of infectious disease in history. There is concern that highly pathogenic avian influenza viruses of the H5 and H7 subtypes may evolve to cause similar pandemics. In humans, influenza viruses infect the respiratory epithelium. The haemagglutinin (HA) proteins of IAV and IBV, or the haemagglutinin-esterase-fusion (HEF) proteins of ICV, bind sialic acid, causing endocytosis. Unusually among RNA viruses, the viral genome replicates in the nucleus. New viruses assemble at the cell surface and are released by the receptor-cleaving neuraminidase (NA) proteins of IAV and IBV or the ICV HEF protein.}, } @article {pmid29908997, year = {2018}, author = {Ivanenko, VN and Hoeksema, BW and Mudrova, SV and Nikitin, MA and Martínez, A and Rimskaya-Korsakova, NN and Berumen, ML and Fontaneto, D}, title = {Lack of host specificity of copepod crustaceans associated with mushroom corals in the Red Sea.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {770-780}, doi = {10.1016/j.ympev.2018.06.024}, pmid = {29908997}, issn = {1095-9513}, abstract = {The radiation of symbiotic copepods (Crustacea: Copepoda) living in association with stony corals (Cnidaria: Scleractinia) is considered host-specific and linked to the phylogenetic diversification of their hosts. However, symbiotic copepods are poorly investigated, occurrence records are mostly anecdotal, and no explicit analysis exists regarding their relationship with the hosts. Here, we analysed the occurrence of symbiotic copepods on different co-occurring and phylogenetically closely related scleractinian corals. We used an innovative approach of DNA extraction from single microscopic specimens that preserves the shape of the organisms for integrative morphological studies. The rationale of the study involved: (i) sampling of mushroom corals (Fungiidae) belonging to 13 species and eight genera on different reefs along the Saudi coastline in the Red Sea, (ii) extraction of all the associated copepods, (iii) morphological screening and identification of copepod species, (iv) use of DNA taxonomy on mitochondrial and nuclear markers to determine species boundaries for morphologically unknown copepod species, (v) reconstruction of phylogenies to understand their evolutionary relationships, and (vi) analysis of the ecological drivers of the occurrence, diversity and host specificity of the copepods. The seven species of coral-associated copepods, all new to science, did not show any statistically significant evidence of host-specificity or other pattern of ecological association. We thus suggest that, contrary to most assumptions and previous anecdotal evidence on this coral-copepod host-symbiont system, the association between copepods and their host corals is rather labile, not strict, and not phylogenetically constrained, changing our perception on evolutionary patterns and processes in symbiotic copepods.}, } @article {pmid29908996, year = {2018}, author = {Adams, NE and Inoue, K and Seidel, RA and Lang, BK and Berg, DJ}, title = {Isolation drives increased diversification rates in freshwater amphipods.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {746-757}, doi = {10.1016/j.ympev.2018.06.022}, pmid = {29908996}, issn = {1095-9513}, abstract = {Vicariance and dispersal events affect current biodiversity patterns in desert springs. Whether major diversification events are due to environmental changes leading to radiation or due to isolation resulting in relict species is largely unknown. We seek to understand whether the Gammarus pecos species complex underwent major diversification events due to environmental changes in the area leading either to radiation into novel habitats, or formation of relicts due to isolation. Specifically, we tested the hypothesis that Gammarus in the northern Chihuahuan Desert of New Mexico and Texas, USA are descendants of an ancient marine lineage now containing multiple undescribed species. We sequenced a nuclear (28S) and two mitochondrial (16S, COI) genes from gammarid amphipods representing 16 desert springs in the northern Chihuahuan Desert. We estimated phylogenetic relationships, divergence times, and diversification rates of the Gammarus pecos complex. Our results revealed that the region contained two evolutionarily independent lineages: a younger Freshwater Lineage that shared a most-recent-common-ancestor with an older Saline Lineage ∼66.3 MYA (95.6-42.4 MYA). Each spring system generally formed a monophyletic clade based on the concatenated dataset. Freshwater Lineage diversification rates were 2.0-9.8 times higher than rates of the Saline Lineage. A series of post-Cretaceous colonizations by ancestral Gammarus taxa was likely followed by isolation. Paleo-geological, hydrological, and climatic events in the Neogene-to-Quaternary periods (23.03 MYA - present) in western North America promoted allopatric speciation of both lineages. We suggest that Saline Lineage populations include two undescribed Gammarus species, while the Freshwater Lineage shows repetition of fine-scale genetic structure in all major clades suggesting incipient speciation. Such ongoing speciation suggests that this region will continue to be a biodiversity hotspot for amphipods and other freshwater taxa.}, } @article {pmid29908995, year = {2018}, author = {Sheng, Y and He, M and Zhao, F and Shao, C and Miao, M}, title = {Phylogenetic relationship analyses of complicated class Spirotrichea based on transcriptomes from three diverse microbial eukaryotes: Uroleptopsis citrina, Euplotes vannus and Protocruzia tuzeti.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {338-345}, doi = {10.1016/j.ympev.2018.06.025}, pmid = {29908995}, issn = {1095-9513}, abstract = {Ciliates are one of the eukaryotic unicellular organisms which are thought to be the oldest life forms, and widely geographically distributed. For a variety of reasons, some groups of ciliates have attracted more attention than others, such as the class Spirotrichea and related species with its complicated evolutionary relationships. In this study, we obtained the transcriptome data of three typical ciliates, Uroleptopsis citrina, Euplotes vannus, Protocruzia tuzeti using high throughput sequencing. The genetic relationships were revealed by phylogenomic analysis of 109 genes comprising of 34,882 amino acid residues, and analyses based on SSU rDNA of 55 species, as well as the comparison of gene content among spirotricheans and related species. Our phylogenomic analyses show the Spirotrichea is monophyletic when Protocruzia is excluded, in which four subclasses: Oligotrichia, Choreotrichia, Hypotrichia and Euplotia also formed momophyletic groups respectively. The Hypotrichia was placed as a sister branch to the assemblage, in which two oligotrichs clustered with two choreotrichs. In addition to this, the Protocruziidia was placed in an independent lineage status out of the Spirotrichea. Together with its high binding-related gene content compared to other species and the significant variation in morphological characters, these findings support the removal of Protocruzia from the class Spirotrichea.}, } @article {pmid29908711, year = {2018}, author = {Bak, RO and Gomez-Ospina, N and Porteus, MH}, title = {Gene Editing on Center Stage.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {600-611}, doi = {10.1016/j.tig.2018.05.004}, pmid = {29908711}, issn = {0168-9525}, abstract = {Smithies et al. (1985) and Jasin and colleagues (1994) provided proof of concept that homologous recombination (HR) could be applied to the treatment of human disease and that its efficiency could be improved by the induction of double-strand breaks (DSBs). A key advance was the discovery of engineered nucleases, such as zinc-finger nucleases (ZFNs) and transcription activator-like (TAL) effector nucleases (TALENs), that can generate site-specific DSBs. The democratization and widespread use of genome editing was enabled by the discovery of the clustered regularly interspaced short palindromic repeats (CRISPR)-Cas9 nuclease system. While genome editing using ZFNs and TALENs has already reached clinical trials, the pace at which genome editing enters human trials is bound to accelerate in the next several years with multiple promising preclinical studies heralding cures for monogenic diseases that are currently difficult to manage or even incurable. Here we review recent advances and current limitations and discuss the path forward using genome editing to understand, treat, and cure genetic diseases.}, } @article {pmid29908710, year = {2018}, author = {Standart, N and Weil, D}, title = {P-Bodies: Cytosolic Droplets for Coordinated mRNA Storage.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {612-626}, doi = {10.1016/j.tig.2018.05.005}, pmid = {29908710}, issn = {0168-9525}, abstract = {P-bodies (PBs) are cytosolic RNP granules that are conserved among eukaryotic organisms. In the past few years, major progress has been made in understanding the biochemical and biophysical mechanisms that lead to their formation. However, whether they play a role in mRNA storage or decay remains actively debated. P-bodies were recently isolated from human cells by a novel fluorescence-activated particle sorting (FAPS) approach that enabled the characterization of their protein and RNA content, providing new insights into their function. Together with recent innovative imaging studies, these new data show that mammalian PBs are primarily involved not in RNA decay but rather in the coordinated storage of mRNAs encoding regulatory functions. These small cytoplasmic droplets could thus be important for cell adaptation to the environment.}, } @article {pmid29908645, year = {2018}, author = {Heneghan, L}, title = {Have Ecologists Lost Their Senses? Walking and Reflection as Ecological Method.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {475-478}, doi = {10.1016/j.tree.2018.04.016}, pmid = {29908645}, issn = {1872-8383}, } @article {pmid29908491, year = {2018}, author = {Huys, GR and Raes, J}, title = {Go with the flow or solitary confinement: a look inside the single-cell toolbox for isolation of rare and uncultured microbes.}, journal = {Current opinion in microbiology}, volume = {44}, number = {}, pages = {1-8}, doi = {10.1016/j.mib.2018.05.002}, pmid = {29908491}, issn = {1879-0364}, abstract = {With the vast majority of the microbial world still considered unculturable or undiscovered, microbiologists not only require more fundamental insights concerning microbial growth requirements but also need to implement miniaturized, versatile and high-throughput technologies to upscale current microbial isolation strategies. In this respect, single-cell-based approaches are increasingly finding their way to the microbiology lab. A number of recent studies have demonstrated that analysis and separation of free microbial cells by flow-based sorting as well as physical stochastic confinement of individual cells in microenvironment compartments can facilitate the isolation of previously uncultured species and the discovery of novel microbial taxa. Still, while most of these methods give immediate access to downstream whole genome sequencing, upscaling to higher cell densities as required for metabolic readouts and preservation purposes can remain challenging. Provided that these and other technological challenges are addressed in future innovation rounds, integration of single-cell tools in commercially available benchtop instruments and service platforms is expected to trigger more targeted explorations in the microbial dark matter at a depth comparable to metagenomics.}, } @article {pmid29908091, year = {2018}, author = {Dorken, ME and Van Drunen, WE}, title = {Life-history trade-offs promote the evolution of dioecy.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1405-1412}, doi = {10.1111/jeb.13335}, pmid = {29908091}, issn = {1420-9101}, support = {//Natural Sciences and Engineering Council of Canada (NSERC)/ ; }, abstract = {Most dioecious plants are perennial and subject to trade-offs between sexual reproduction and vegetative performance. However, these broader life-history trade-offs have not usually been incorporated into theoretical analyses of the evolution of separate sexes. One such analysis has indicated that hermaphroditism is favoured over unisexuality when female and male sex functions involve the allocation of nonoverlapping types of resources to each sex function (e.g. allocations of carbon to female function vs. allocations of nitrogen to male function). However, some dioecious plants appear to conform to this pattern of resource allocation, with different resource types allocated to female vs. male sex functions. Using an evolutionarily stable strategy approach, we show that life-history trade-offs between sexual reproduction and vegetative performance enable the evolution of unisexual phenotypes even when there are no direct resource-based trade-offs between female and male sex functions. This result might help explain the preponderance of perennial life histories among dioecious plants and why many dioecious plants with annual life histories have indeterminate growth with ongoing trade-offs between sexual reproduction and vegetative growth.}, } @article {pmid29907938, year = {2018}, author = {Li, W and Hou, Q and Wang, Y and Ma, H and Liu, Y and Zhao, F and Li, J and Kwok, LY and Yu, J and Sun, Z and Sun, T}, title = {Analysis of the Gut Microbial Diversity of Dairy Cows During Peak Lactation by PacBio Single-Molecule Real-Time (SMRT) Sequencing.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1316-1323}, pmid = {29907938}, issn = {1432-0991}, mesh = {Animals ; Bacteria/classification/genetics/*isolation & purification/metabolism ; *Biodiversity ; Cattle/*microbiology/physiology ; DNA, Bacterial/genetics ; Fatty Acids, Volatile/metabolism ; Female ; *Gastrointestinal Microbiome ; Intestines/*microbiology ; Lactation ; Metagenome ; Milk/metabolism ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: The gut microbes of dairy cows are strongly associated with their health, but the relationship between milk production and the intestinal microbiota has seldom been studied. Thus, we explored the diversity of the intestinal microbiota during peak lactation of dairy cows.

METHODS: The intestinal microbiota of nine dairy cows at peak lactation was evaluated using the Pacific Biosciences single-molecule real-time (PacBio SMRT) sequencing approach.

RESULTS: A total of 32,670 high-quality 16S rRNA gene sequences were obtained, belonging to 12 phyla, 59 families, 107 genera, and 162 species. Firmicutes (83%) were the dominant phylum, while Bacteroides (6.16%) was the dominant genus. All samples showed a high microbial diversity, with numerous genera of short chain fatty acid (SCFA)-producers. The proportion of SCFA producers was relatively high in relation to the identified core intestinal microbiota. Moreover, the predicted functional metagenome was heavily involved in energy metabolism.

CONCLUSIONS: This study provided novel insights into the link between the dairy cow gut microbiota and milk production.}, } @article {pmid29907823, year = {2018}, author = {Beerman, I}, title = {Cell umbrella protects stem cells from DNA damage.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {374-375}, pmid = {29907823}, issn = {1476-4687}, support = {Z99 AG999999//NULL/International ; }, mesh = {*DNA Damage ; DNA Repair ; Stem Cells ; *Ultraviolet Rays ; }, } @article {pmid29907822, year = {2018}, author = {Kuffner, IB}, title = {Sea-level rise could overwhelm coral reefs.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {378-379}, doi = {10.1038/d41586-018-04879-7}, pmid = {29907822}, issn = {1476-4687}, mesh = {Animals ; *Anthozoa ; Climate Change ; *Coral Reefs ; Ecosystem ; }, } @article {pmid29907821, year = {2018}, author = {Hendriks, L and Besse, B}, title = {New windows open for immunotherapy in lung cancer.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {376-377}, doi = {10.1038/d41586-018-05312-9}, pmid = {29907821}, issn = {1476-4687}, mesh = {Cancer Vaccines ; Humans ; Immunotherapy ; Lung Neoplasms ; *Neoadjuvant Therapy ; Neoplasms ; *Programmed Cell Death 1 Receptor ; }, } @article {pmid29907820, year = {2018}, author = {Samuelson, LC}, title = {Debate over the identity of an intestinal niche-cell population settled.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {380-381}, doi = {10.1038/d41586-018-05281-z}, pmid = {29907820}, issn = {1476-4687}, mesh = {Cell Differentiation ; *Intestines ; *Stem Cell Niche ; Telocytes ; }, } @article {pmid29907793, year = {2018}, author = {Uchida, KI and Daimon, S and Iguchi, R and Saitoh, E}, title = {Publisher Correction: Observation of anisotropic magneto-Peltier effect in nickel.}, journal = {Nature}, volume = {560}, number = {7720}, pages = {E36}, doi = {10.1038/s41586-018-0248-2}, pmid = {29907793}, issn = {1476-4687}, abstract = {In this Letter, owing to an error during the production process, 'θH' was incorrectly written as 'θΗH' six times in the paragraph starting "Up to now,…". These errors have been corrected online.}, } @article {pmid29907763, year = {2018}, author = {Koch, L}, title = {All eyes on rapid adaptive evolution.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {472}, doi = {10.1038/s41576-018-0027-9}, pmid = {29907763}, issn = {1471-0064}, } @article {pmid29907761, year = {2018}, author = {York, A}, title = {Sharing the burden to build a matrix.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0045-9}, pmid = {29907761}, issn = {1740-1534}, } @article {pmid29907611, year = {2018}, author = {Agarwal, AK}, title = {How to explain the AKT phosphorylation of downstream targets in the wake of recent findings.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6099-E6100}, pmid = {29907611}, issn = {1091-6490}, support = {R01 DK105448/DK/NIDDK NIH HHS/United States ; }, mesh = {Phosphatidylinositol 3-Kinases ; Phosphorylation ; *Proto-Oncogene Proteins c-akt ; *Signal Transduction ; }, } @article {pmid29907610, year = {2018}, author = {Leonard, TA}, title = {Reply to Agarwal: Activity against nuclear substrates is not necessarily mediated by nuclear Akt.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6101-E6102}, pmid = {29907610}, issn = {1091-6490}, mesh = {*Cell Nucleus ; Phosphorylation ; *Proto-Oncogene Proteins c-akt ; }, } @article {pmid29907131, year = {2018}, author = {Muraki, M and Hirota, K}, title = {Confirmation of covalently-linked structure and cell-death inducing activity in site-specific chemical conjugates of human Fas ligand extracellular domain.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {395}, pmid = {29907131}, issn = {1756-0500}, mesh = {*Cell Death ; Extracellular Space/*chemistry ; Fas Ligand Protein/*chemistry ; Humans ; Protein Binding ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {OBJECTIVE: In this study, we aimed to identify the structural components and to clarify the biological activity in the site-specific conjugates of human Fas ligand extracellular domain (hFasLECD) with either fluorescein moiety (FL) or chicken egg-white avidin (Avi). The conjugates were characterized by molecular-weight measurement using MALDI-TOF mass-spectrometric analysis and by cell-death inducing activity measurement against a human colorectal cancer cell line, HT-29, using MTT cell-viability assay. Pretreatment effect with human interferon-γ (IFN-γ) on the cell-death inducing activity was evaluated.

RESULTS: The mass-spectrometric analysis of the hFasLECD-Avi conjugate showed that it was possible to detect the signal peak of molecular-weight to electric charge (m/z) derived from the component involved in the covalent linking as the sum of the molecular-weight of unconjugated hFasLECD- and Avi-derivative subunits, in addition to the signals from each corresponding subunit component irrelevant to the covalent linking. The cell-viability assay revealed that both conjugates possessed a remarkable death-inducing activity against HT-29 cells in synergy with the pretreatment using human IFN-γ. Following 24 h pretreatment with 100 IU/ml of human IFN-γ, almost no viable cells existed after 72 h treatment with either 100 or 1000 ng/ml of FL-hFasLECD and hFasLECD-Avi conjugates.}, } @article {pmid29907125, year = {2018}, author = {Beveridge, LA and Price, RJG and Burton, LA and Witham, MD and Struthers, AD and Sumukadas, D}, title = {Acceptability and feasibility of magnetic femoral nerve stimulation in older, functionally impaired patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {394}, pmid = {29907125}, issn = {1756-0500}, support = {CZH/4/1100//Chief Scientist Office/United Kingdom ; }, mesh = {*Activities of Daily Living ; Aged ; Aged, 80 and over ; Feasibility Studies ; Female ; Femoral Nerve/*physiology ; Humans ; Magnetic Field Therapy/*methods ; Male ; *Outcome Assessment (Health Care) ; *Patient Acceptance of Health Care ; Quadriceps Muscle/*physiopathology ; Reproducibility of Results ; Sarcopenia/*therapy ; }, abstract = {OBJECTIVE: Magnetic femoral nerve stimulation to test muscle function has been largely unexplored in older people. We assessed acceptability, feasibility, along with reproducibility and correlation with other physical function measures.

RESULTS: Study 1 recruited older people with sarcopenia. Stimulation was performed at baseline and 2 weeks along with six minute walk (6MW), maximum voluntary quadriceps contraction, short physical performance battery and grip strength. Acceptability was measured using visual analog scales. Study 2 used baseline data from a trial of older people. We correlated stimulation results with 6MW, maximal voluntary contraction and muscle mass. Maximum quadriceps twitch tension was measured in both studies, evoked using biphasic magnetic stimulation of the femoral nerve. In study 1 (n = 12), magnetic stimulation was well tolerated with mean discomfort rating of 9% (range 0-40%) on a visual analog scale. Reproducibility was poor (intraclass correlation coefficient 0.06; p = 0.44). Study 2 (n = 64) showed only weak to moderate correlations for maximum quadriceps twitch tension with other measures of physical function (6 minute walk test r = 0.24, p = 0.06; maximal voluntary contraction r = 0.26; p = 0.04). We conclude that magnetic femoral nerve stimulation is acceptable and feasible but poorly reproducible in older, functionally impaired people.}, } @article {pmid29907104, year = {2018}, author = {McNally, CP and Borenstein, E}, title = {Metabolic model-based analysis of the emergence of bacterial cross-feeding via extensive gene loss.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {69}, pmid = {29907104}, issn = {1752-0509}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; T32 HG000035//National Human Genome Research Institute/ ; T32 HG000035/HG/NHGRI NIH HHS/United States ; DP2 AT007802-01//National Institutes of Health/ ; 1R01GM124312-01//National Institutes of Health (US)/ ; R01 GM124312/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Metabolic dependencies between microbial species have a significant impact on the assembly and activity of microbial communities. However, the evolutionary origins of such dependencies and the impact of metabolic and genomic architecture on their emergence are not clear.

RESULTS: To address these questions, we developed a novel framework, coupling a reductive evolution model with a multi-species genome-scale metabolic model to simulate the evolution of two-species microbial communities. Simulating thousands of independent evolutionary trajectories, we surprisingly found that under certain environmental and evolutionary settings metabolic dependencies emerged frequently even though our model does not include explicit selection for cooperation. Evolved dependencies involved cross-feeding of a diverse set of metabolites, reflecting constraints imposed by metabolic network architecture. We additionally found metabolic 'missed opportunities', wherein species failed to capitalize on metabolites made available by their partners. Examining the genes deleted in each evolutionary trajectory and the deletion timing further revealed both genome-wide properties and specific metabolic mechanisms associated with species interaction.

CONCLUSION: Our findings provide insight into the evolution of cooperative interaction among microbial species and a unique view into the way such relationships emerge.}, } @article {pmid29907103, year = {2018}, author = {Strunov, A and Boldyreva, LV and Andreyeva, EN and Pavlova, GA and Popova, JV and Razuvaeva, AV and Anders, AF and Renda, F and Pindyurin, AV and Gatti, M and Kiseleva, E}, title = {Ultrastructural analysis of mitotic Drosophila S2 cells identifies distinctive microtubule and intracellular membrane behaviors.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {68}, pmid = {29907103}, issn = {1741-7007}, abstract = {BACKGROUND: S2 cells are one of the most widely used Drosophila melanogaster cell lines. A series of studies has shown that they are particularly suitable for RNAi-based screens aimed at the dissection of cellular pathways, including those controlling cell shape and motility, cell metabolism, and host-pathogen interactions. In addition, RNAi in S2 cells has been successfully used to identify many new mitotic genes that are conserved in the higher eukaryotes, and for the analysis of several aspects of the mitotic process. However, no detailed and complete description of S2 cell mitosis at the ultrastructural level has been done. Here, we provide a detailed characterization of all phases of S2 cell mitosis visualized by transmission electron microscopy (TEM).

RESULTS: We analyzed by TEM a random sample of 144 cells undergoing mitosis, focusing on intracellular membrane and microtubule (MT) behaviors. This unbiased approach provided a comprehensive ultrastructural view of the dividing cells, and allowed us to discover that S2 cells exhibit a previously uncharacterized behavior of intracellular membranes, involving the formation of a quadruple nuclear membrane in early prometaphase and its disassembly during late prometaphase. After nuclear envelope disassembly, the mitotic apparatus becomes encased by a discontinuous network of endoplasmic reticulum membranes, which associate with mitochondria, presumably to prevent their diffusion into the spindle area. We also observed a peculiar metaphase spindle organization. We found that kinetochores with attached k-fibers are almost invariably associated with lateral MT bundles that can be either interpolar bundles or k-fibers connected to a different kinetochore. This spindle organization is likely to favor chromosome alignment at metaphase and subsequent segregation during anaphase.

CONCLUSIONS: We discovered several previously unknown features of membrane and MT organization during S2 cell mitosis. The genetic determinants of these mitotic features can now be investigated, for instance by using an RNAi-based approach, which is particularly easy and efficient in S2 cells.}, } @article {pmid29907097, year = {2018}, author = {Oudah, M and Henschel, A}, title = {Taxonomy-aware feature engineering for microbiome classification.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {227}, pmid = {29907097}, issn = {1471-2105}, abstract = {BACKGROUND: What is a healthy microbiome? The pursuit of this and many related questions, especially in light of the recently recognized microbial component in a wide range of diseases has sparked a surge in metagenomic studies. They are often not simply attributable to a single pathogen but rather are the result of complex ecological processes. Relatedly, the increasing DNA sequencing depth and number of samples in metagenomic case-control studies enabled the applicability of powerful statistical methods, e.g. Machine Learning approaches. For the latter, the feature space is typically shaped by the relative abundances of operational taxonomic units, as determined by cost-effective phylogenetic marker gene profiles. While a substantial body of microbiome/microbiota research involves unsupervised and supervised Machine Learning, very little attention has been put on feature selection and engineering.

RESULTS: We here propose the first algorithm to exploit phylogenetic hierarchy (i.e. an all-encompassing taxonomy) in feature engineering for microbiota classification. The rationale is to exploit the often mono- or oligophyletic distribution of relevant (but hidden) traits by virtue of taxonomic abstraction. The algorithm is embedded in a comprehensive microbiota classification pipeline, which we applied to a diverse range of datasets, distinguishing healthy from diseased microbiota samples.

CONCLUSION: We demonstrate substantial improvements over the state-of-the-art microbiota classification tools in terms of classification accuracy, regardless of the actual Machine Learning technique while using drastically reduced feature spaces. Moreover, generalized features bear great explanatory value: they provide a concise description of conditions and thus help to provide pathophysiological insights. Indeed, the automatically and reproducibly derived features are consistent with previously published domain expert analyses.}, } @article {pmid29907096, year = {2018}, author = {Hallahan, BF and Fernandez-Tendero, E and Fort, A and Ryder, P and Dupouy, G and Deletre, M and Curley, E and Brychkova, G and Schulz, B and Spillane, C}, title = {Hybridity has a greater effect than paternal genome dosage on heterosis in sugar beet (Beta vulgaris).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {120}, pmid = {29907096}, issn = {1471-2229}, support = {13/IA/1820//Science Foundation Ireland/Ireland ; GOIPG/2014/1021//Irish Research Council/ ; }, mesh = {Beta vulgaris/*genetics/growth & development ; Diploidy ; Gene Dosage/*genetics ; Genes, Plant/genetics ; Hybrid Vigor/*genetics ; Hybridization, Genetic/*genetics ; Hydroxyethylrutoside ; Plant Roots/growth & development ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait, Heritable ; Seedlings/growth & development ; Sequence Analysis, DNA ; Sugars/metabolism ; Triploidy ; }, abstract = {BACKGROUND: The phenomenon of heterosis is critical to plant breeding and agricultural productivity. Heterosis occurs when F1 hybrid offspring display quantitative improvements in traits to levels that do not occur in the parents. Increasing the genome dosage (i.e. ploidy level) of F1 offspring can contribute to heterosis effects. Sugar beet (Beta vulgaris) provides a model for investigating the relative effects of genetic hybridity and genome dosage on heterosis. Sugar beet lines of different ploidy levels were crossed to generate diploid and triploid F1 offspring to investigate the effect of; (1) paternal genome dosage increase on F1 heterosis, and; (2) homozygous versus heterozygous tetraploid male parents on F1 triploid heterosis. A range of traits of agronomic and commercial importance were analyzed for the extent of heterosis effects observed in the F1 offspring.

RESULTS: Comparisons of parental lines to diploid (EA, EB) and triploid (EAA, EBB) F1 hybrids for total yield, root yield, and sugar yield indicated that there was no effect of paternal genome dosage increases on heterosis levels, indicating that hybridity is the main contributor to the heterosis levels observed. For all traits measured (apart from seed viability), F1 triploid hybrids derived from heterozygous tetraploid male parents displayed equivalent levels of heterosis as F1 triploid hybrids generated with homozygous tetraploid male parents, suggesting that heterosis gains in F1 triploids do not arise by simply increasing the extent of multi-locus heterozygosity in sugar beet F1 offspring.

CONCLUSIONS: Overall, our study indicates that; (1) increasing the paternal genome dosage does not enhance heterosis in F1 hybrids, and; (2) increasing multi-locus heterozygosity using highly heterozygous paternal genomes to generate F1 triploid hybrids does not enhance heterosis. Our findings have implications for the design of future F1 hybrid improvement programs for sugar beet.}, } @article {pmid29907088, year = {2018}, author = {Richard Albert, J and Koike, T and Younesy, H and Thompson, R and Bogutz, AB and Karimi, MM and Lorincz, MC}, title = {Development and application of an integrated allele-specific pipeline for methylomic and epigenomic analysis (MEA).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {463}, pmid = {29907088}, issn = {1471-2164}, support = {I01 RX001141/RX/RRD VA/United States ; I21 RX001583/RX/RRD VA/United States ; MOP-133417//Canadian Institutes of Health Research/Canada ; RGPIN-2015-05228//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {*Alleles ; Animals ; Chromatin Immunoprecipitation ; CpG Islands ; *DNA Methylation ; *Epigenesis, Genetic ; Epigenomics/*methods ; Gene Expression Profiling ; Germ Cells/metabolism ; Humans ; INDEL Mutation ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; *Software ; Transcription Initiation Site ; }, abstract = {BACKGROUND: Allele-specific transcriptional regulation, including of imprinted genes, is essential for normal mammalian development. While the regulatory regions controlling imprinted genes are associated with DNA methylation (DNAme) and specific histone modifications, the interplay between transcription and these epigenetic marks at allelic resolution is typically not investigated genome-wide due to a lack of bioinformatic packages that can process and integrate multiple epigenomic datasets with allelic resolution. In addition, existing ad-hoc software only consider SNVs for allele-specific read discovery. This limitation omits potentially informative INDELs, which constitute about one fifth of the number of SNVs in mice, and introduces a systematic reference bias in allele-specific analyses.

RESULTS: Here, we describe MEA, an INDEL-aware Methylomic and Epigenomic Allele-specific analysis pipeline which enables user-friendly data exploration, visualization and interpretation of allelic imbalance. Applying MEA to mouse embryonic datasets yields robust allele-specific DNAme maps and low reference bias. We validate allele-specific DNAme at known differentially methylated regions and show that automated integration of such methylation data with RNA- and ChIP-seq datasets yields an intuitive, multidimensional view of allelic gene regulation. MEA uncovers numerous novel dynamically methylated loci, highlighting the sensitivity of our pipeline. Furthermore, processing and visualization of epigenomic datasets from human brain reveals the expected allele-specific enrichment of H3K27ac and DNAme at imprinted as well as novel monoallelically expressed genes, highlighting MEA's utility for integrating human datasets of distinct provenance for genome-wide analysis of allelic phenomena.

CONCLUSIONS: Our novel pipeline for standardized allele-specific processing and visualization of disparate epigenomic and methylomic datasets enables rapid analysis and navigation with allelic resolution. MEA is freely available as a Docker container at https://github.com/julienrichardalbert/MEA .}, } @article {pmid29907083, year = {2018}, author = {Qi, W and Chen, X and Fang, P and Shi, S and Li, J and Liu, X and Cao, X and Zhao, N and Hao, H and Li, Y and Han, Y and Zhang, Z}, title = {Genomic and transcriptomic sequencing of Rosa hybrida provides microsatellite markers for breeding, flower trait improvement and taxonomy studies.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {119}, pmid = {29907083}, issn = {1471-2229}, support = {31501791//National Natural Science Foundation of China/ ; 31772344//National Natural Science Foundation of China/ ; 6162017//Natural Science Foundation of Beijing Municipality/ ; }, mesh = {DNA, Plant/genetics ; Flowers/*anatomy & histology ; Gene Expression Profiling ; Genome, Plant/genetics ; Microsatellite Repeats/*genetics ; Plant Breeding/*methods ; Polymerase Chain Reaction ; Quantitative Trait, Heritable ; Rosa/anatomy & histology/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Rosa hybrida is a valuable ornamental, food and medicinal crop worldwide, but with relatively limited molecular marker resources, especially for flower-specific markers. In this study, we performed genomic and floral transcriptomic sequencing of modern rose. We obtained comprehensive nucleotide information, from which numerous potential simple sequence repeat (SSR) markers were identified but were found to have high rates of amplification failure and PCR product redundancy.

RESULTS: We applied a filtering strategy for BLAST analysis with the assembled genomic sequence and identified 124,591 genomic and 2,292 EST markers with unique annealing sites. These markers had much greater reliability than those obtained before filtering. Additional BLAST analysis against the transcriptomic sequences uncovered 5225 genomic SSRs associated with 4100 transcripts, 2138 of which were associated with functional genes that were annotated against the non-redundant database. More than 90% of these newly developed molecular markers were polymorphic, based on PCR using a subset of SSRs to analyze tetraploid modern rose accessions, diploid Rosa species and one strawberry accession. The relationships among Rosa species determined by cluster analysis (based on these results) were in agreement with modern rose breeding history, whereas strawberry was isolated in a separate cluster, as expected.

CONCLUSIONS: Our results provide valuable molecular-genetic tools for rose flower trait improvement, breeding and taxonomy. Importantly, we describe a reproducible organ-specific strategy for molecular marker development and selection in plants, which can be applied to other crops.}, } @article {pmid29907081, year = {2018}, author = {Kadekar, P and Chaouni, R and Clark, E and Kazanets, A and Roy, R}, title = {Genome-wide surveys reveal polarity and cytoskeletal regulators mediate LKB1-associated germline stem cell quiescence.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {462}, pmid = {29907081}, issn = {1471-2164}, mesh = {Actin Cytoskeleton/*ultrastructure ; Animals ; Caenorhabditis elegans/cytology/genetics/growth & development/ultrastructure ; Caenorhabditis elegans Proteins/*genetics ; Cell Polarity/genetics ; Cytoskeleton ; Genome ; Germ Cells/*cytology/ultrastructure ; Hyperplasia ; Larva/cytology/genetics/ultrastructure ; Mutation ; Protein Kinases/genetics ; Protein-Serine-Threonine Kinases/*genetics ; RNA Interference ; Stem Cells/*cytology ; }, abstract = {BACKGROUND: Caenorhabditis elegans can endure long periods of environmental stress by altering their development to execute a quiescent state called "dauer". Previous work has implicated LKB1 - the causative gene in the autosomal dominant, cancer pre-disposing disease called Peutz-Jeghers Syndrome (PJS), and its downstream target AMPK, in the establishment of germline stem cell (GSC) quiescence during the dauer stage. Loss of function mutations in both LKB1/par-4 and AMPK/aak(0) result in untimely GSC proliferation during the onset of the dauer stage, although the molecular mechanism through which these factors regulate quiescence remains unclear. Curiously, the hyperplasia observed in par-4 mutants is more severe than AMPK-compromised dauer larvae, suggesting that par-4 has alternative downstream targets in addition to AMPK to regulate germline quiescence.

RESULTS: We conducted three genome-wide RNAi screens to identify potential downstream targets of the protein kinases PAR-4 and AMPK that mediate dauer-dependent GSC quiescence. First, we screened to identify genes that phenocopy the par-4-dependent hyperplasia when compromised by RNAi. Two additional RNAi screens were performed to identify genes that suppressed the germline hyperplasia in par-4 and aak(0) dauer larvae, respectively. Interestingly, a subset of the candidates we identified are involved in the regulation of cell polarity and cytoskeletal function downstream of par-4, in an AMPK-independent manner. Moreover, we show that par-4 temporally regulates actin cytoskeletal organization within the dauer germ line at the rachis-adjacent membrane, in an AMPK-independent manner.

CONCLUSION: Our data suggest that the regulation of the cytoskeleton and cell polarity may contribute significantly to the tumour suppressor function of LKB1/par-4.}, } @article {pmid29907080, year = {2018}, author = {Jueterbock, A and Coyer, JA and Olsen, JL and Hoarau, G}, title = {Decadal stability in genetic variation and structure in the intertidal seaweed Fucus serratus (Heterokontophyta: Fucaceae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {94}, pmid = {29907080}, issn = {1471-2148}, support = {196505//Norges Forskningsråd/International ; PL95-0076//EU-MAST-3 BIOGAP/International ; PL97-12670//EU-MAST-3 BIOBASE/International ; 813.04.008//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/International ; 815-01.011//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NL)/International ; GOCE-CT-2003-505446//EU-FP6-Network of Excellence, MarBEF/International ; GOCE-CT-2004-505403//EU-FP6-Network of Excellence, Marine-Genomics-Europe/International ; }, mesh = {Cluster Analysis ; France ; Fucus/*genetics ; *Genetic Variation ; Microsatellite Repeats ; Population Density ; Seaweed/*genetics ; Temperature ; *Water Movements ; }, abstract = {BACKGROUND: The spatial distribution of genetic diversity and structure has important implications for conservation as it reveals a species' strong and weak points with regard to stability and evolutionary capacity. Temporal genetic stability is rarely tested in marine species other than commercially important fishes, but is crucial for the utility of temporal snapshots in conservation management. High and stable diversity can help to mitigate the predicted northward range shift of seaweeds under the impact of climate change. Given the key ecological role of fucoid seaweeds along rocky shores, the positive effect of genetic diversity may reach beyond the species level to stabilize the entire intertidal ecosystem along the temperate North Atlantic. In this study, we estimated the effective population size, as well as temporal changes in genetic structure and diversity of the seaweed F. serratus using 22 microsatellite markers. Samples were taken across latitudes and a range of temperature regimes at seven locations with decadal sampling (2000 and 2010).

RESULTS: Across latitudes, genetic structure and diversity remained stable over 5-10 generations. Stable small-scale structure enhanced regional diversity throughout the species' range. In accordance with its biogeographic history, effective population size and diversity peaked in the species' mid-range in Brittany (France), and declined towards its leading and trailing edge to the north and south. At the species' southern edge, multi-locus-heterozygosity displayed a strong decline from 1999 to 2010.

CONCLUSION: Temporally stable genetic structure over small spatial scales is a potential driver for local adaptation and species radiation in the genus Fucus. Survival and adaptation of the low-diversity leading edge of F. serratus may be enhanced by regional gene flow and 'surfing' of favorable mutations or impaired by the accumulation of deleterious mutations. Our results have clear implications for the conservation of F. serratus at its genetically unique southern edge in Northwest Iberia, where increasing temperatures are likely the major cause for the decline not only of F. serratus, but also other intertidal and subtidal macroalgae. We expect that F. serratus will disappear from Northwest Iberia by 2100 if genetic rescue is not induced by the influx of genetic variation from Brittany.}, } @article {pmid29906611, year = {2018}, author = {Liang, B and Zhou, RB and Liu, YL and Chen, B and Grismer, LL and Wang, N}, title = {Renewed classification within Goniurosaurus (Squamata: Eublepharidae) uncovers the dual roles of a continental island (Hainan) in species evolution.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {646-654}, doi = {10.1016/j.ympev.2018.06.011}, pmid = {29906611}, issn = {1095-9513}, abstract = {Continental islands are often dynamic in regard to the origin and evolution of their biota. Although colonizations from mainland Southeast Asia to Hainan Island have been reported, the role of Hainan Island as a source for continental biota has not been considered. Goniurosaurus is a genus comprised of nocturnal ground geckos. We reexamined the evolutionary history of Goniurosaurus using both molecular phylogenetics and morphological comparisons. All phylogenetic trees recovered G. zhoui as sister to G. hainanensis + G. lichtenfelderi, which together are the sister lineage of G. bawanglingensis. The recovery of this "Hainan clade" contradicts previous classifications that placed G. bawanglingensis within the G. luii group. Moreover, ancestral trait reconstruction revealed that body band number might have decreased two or three times independently within Goniurosaurus from four to three. The divergence between the continental G. luii group and the Hainan clade was estimated at ∼34.7 Mya (CI = 22.3-48.6), possibly correlating with the vicariance event between Hainan Island and the mainland. G. lichtenfelderi diverged from G. hainanensis very recently, which might be associated with a historical dispersal event from Hainan Island to Vietnam during glacial periods. Our study improves the understanding of Goniurosaurus systematics and reveals the important role of Hainan Island in bidirectional colonizations.}, } @article {pmid29906610, year = {2018}, author = {Silva, SM and Agne, CE and Aleixo, A and Bonatto, SL}, title = {Phylogeny and systematics of Chiroxiphia and Antilophia manakins (Aves, Pipridae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {706-711}, doi = {10.1016/j.ympev.2018.06.016}, pmid = {29906610}, issn = {1095-9513}, abstract = {Chiroxiphia and Antilophia manakins are recognized as closely related genera. Nonetheless, Chiroxiphia has been recovered as paraphyletic in some studies with limited taxonomic coverage. This genus currently comprises five species, although this arrangement is still unsettled. Chiroxiphia pareola is the most widespread species, with four recognized subspecies, but their taxonomic status are also uncertain. Finally, the phylogenetic relationships amongst the majority of Chiroxiphia and Antilophia taxa are unknown. Here, we use multilocus DNA sequences from multiple individuals of all currently accepted species and subspecies of both genera to infer their phylogenetic relationships and its implications on their classification. Our results suggest Chiroxiphia, as currently defined, is a paraphyletic group, since C. boliviana is more closely related to Antilophia than to the remaining Chiroxiphia taxa. Within C. pareola, our results support that C. p. regina and C. p. napensis should be treated as independent species. We found three divergent clades in C. p. pareola likely corresponding to distinct subspecies: one in which the isolated and endemic Tobago Island C. p. atlantica individuals are grouped with C. p. pareola from the north bank of the lower Amazon River; and two sister clades comprising individuals distributed south of the Amazon river, and those from the Atlantic Forest.}, } @article {pmid29906609, year = {2018}, author = {Ahmadi, M and Naderi, M and Kaboli, M and Nazarizadeh, M and Karami, M and Beitollahi, SM}, title = {Evolutionary applications of phylogenetically-informed ecological niche modelling (ENM) to explore cryptic diversification over cryptic refugia.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {712-722}, doi = {10.1016/j.ympev.2018.06.019}, pmid = {29906609}, issn = {1095-9513}, abstract = {We used the fat dormouse (Glis glis), a species from a monotypic genus of family Gliridae, as a model to promote the understanding of patterns of cryptic diversification along the ancient Hyrcanian Forests, one of the old-growth relicts of the temperate deciduous forests worldwide. Mitochondrial Cytb data was used to investigate the phylogenetic status of two geographically-different populations of G. glis along the Hyrcanian Forests among all the worldwide known lineages of the species. Regarding phylogenetically informed partitioning of occurrence data, we then used two analytically different ENMs (i.e. environmental-space and geographic-space) to address whether niche divergence conforms G. glis diversification over the study area. Phylogenetic reconstruction showed significant heterogeneity between other fat dormouse lineages and those belonging to the Hyrcanian Forests as well as within the two hypothesized cryptic groups in the study area. Quantifying niche differences using the two ENM frameworks additionally confirmed divergence between the two cryptic lineages by indicating niche conservatism. The integration of phylogeny and ENM in this study confirms the development of distinct cryptic species and suggests that the Hyrcanian Forests, a well-known Pleistocene refugium, might contain multiple cryptic refugia for small forest-dwelling species during paleontological oscillations.}, } @article {pmid29906608, year = {2018}, author = {Almendra, AL and González-Cózatl, FX and Engstrom, MD and Rogers, DS}, title = {Evolutionary relationships and climatic niche evolution in the genus Handleyomys (Sigmodontinae: Oryzomyini).}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {12-25}, doi = {10.1016/j.ympev.2018.06.018}, pmid = {29906608}, issn = {1095-9513}, abstract = {Mesoamerica is considered a biodiversity hot spot with levels of endemism and species diversity likely underestimated. Unfortunately, the region continues to experience some of the highest deforestation rates in the world. For mammals, the evolutionary relationships of many endemic taxa are controversial, as it is the case for members of the genus Handleyomys. Estimation of a time-calibrated hypothesis for the evolution of these six genera (Euryoryzomys, Handleyomys, Hylaeamys, Nephelomys, Oecomys and Transandinomys) supported a monophyletic Handleyomys sensu lato. Based on their distinctive morphology and the amount of inter-generic genetic divergence, Handleyomys sensu stricto, H. alfaroi, the H. chapmani, and the H. melanotis species groups warrant recognition as separate genera. In addition, species delimitation documents the existence of cryptic species-level lineages within H. alfaroi and H. rostratus. Cryptic lineages within H. rostratus exhibited significant niche differentiation, but this was not the pattern among species-level clades within H. alfaroi. Similarly, age-range correlations revealed that niche evolution within Handleyomys is not correlated with evolutionary time, instead, ancestral climate tolerance reconstructions show niche disparities at specific diversification events within the chapmani and melanotis species groups, while the climatic niche of the rest of species of Handleyomys tended to be conservative.}, } @article {pmid29906607, year = {2018}, author = {Fang, B and Merilä, J and Ribeiro, F and Alexandre, CM and Momigliano, P}, title = {Worldwide phylogeny of three-spined sticklebacks.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {613-625}, doi = {10.1016/j.ympev.2018.06.008}, pmid = {29906607}, issn = {1095-9513}, abstract = {Stickleback fishes in the family Gasterosteidae have become model organisms in ecology and evolutionary biology. However, even in the case of the most widely studied species in this family - the three-spined stickleback (Gasterosteus aculeatus) - the worldwide phylogenetic relationships and colonization history of the different populations and lineages remain poorly resolved. Using a large collection of samples covering most parts of the species distribution range, we subjected thousands of single nucleotide polymorphisms to coalescent analyses in order to reconstruct a robust worldwide phylogeny of extant G. aculeatus populations, as well as their ancestral geographic distributions using Statistical-Dispersal Vicariance and Bayesian Binary MCMC analyses. The results suggest that contemporary populations originated from the Pacific Ocean in the Late Pleistocene, and the Atlantic was colonized through the Arctic Ocean by a lineage that diverged from Pacific sticklebacks ca 44.6 Kya. This lineage contains two branches: one that is distributed in the Mediterranean area, from the Iberian Peninsula to the Black Sea ('Southern European Clade'), and another that is comprised of populations from northern Europe and the east coast of North America ('Trans-Atlantic Clade'). Hence, the results suggest that the North American East Coast was colonized by trans-Atlantic migration. Coalescence-based divergence time estimates suggest that divergence among major clades is much more recent than previously estimated.}, } @article {pmid29906606, year = {2018}, author = {Lanna, FM and Werneck, FP and Gehara, M and Fonseca, EM and Colli, GR and Sites, JW and Rodrigues, MT and Garda, AA}, title = {The evolutionary history of Lygodactylus lizards in the South American open diagonal.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {638-645}, doi = {10.1016/j.ympev.2018.06.010}, pmid = {29906606}, issn = {1095-9513}, abstract = {The Pleistocenic Arc Hypothesis (PAH) posits that South American Seasonally Dry Tropical Forests (SDTF) were interconnected during Pleistocene glacial periods, enabling the expansion of species ranges that were subsequently fragmented in interglacial periods, promoting speciation. The lizard genus Lygodactylus occurs in Africa, Madagascar, and South America. Compared to the high diversity of African Lygodactylus, only two species are known to occur in South America, L. klugei and L. wetzeli, distributed in SDTFs and the Chaco, respectively. We use a phylogenetic approach based on mitochondrial (ND2) and nuclear (RAG-1) markers covering the known range of South American Lygodactylus to investigate (i) if they are monophyletic relative to their African congeners, (ii) if their divergence is congruent with the fragmentation of the PAH, and (iii) if cryptic diversity exists within currently recognized species. Maximum likelihood and Bayesian phylogenetic analyses recovered a well-supported monophyletic South American Lygodactylus, presumably resulting from a single trans-Atlantic dispersal event 29 Mya. Species delimitation analyses supported the existence of five putative species, three of them undescribed. Divergence times among L. klugei and the three putative undescribed species, all endemic to the SDTFs, are not congruent with the fragmentation of the PAH. However, fragmentation of the once broader and continuous SDTFs likely influenced the divergence of L. wetzeli in the Chaco and Lygodactylus sp. 3 (in a SDTF enclave in the Cerrado).}, } @article {pmid29906605, year = {2018}, author = {Román-Palacios, C and Tavera, J and Castañeda, MDR}, title = {When did anoles diverge? An analysis of multiple dating strategies.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {655-668}, doi = {10.1016/j.ympev.2018.06.012}, pmid = {29906605}, issn = {1095-9513}, abstract = {Whereas most of the studies that discuss the evolutionary divergence of Anolis lizards have dated the clade's crown group in between 31 and 64 Ma, a single study has recovered a significantly older age for the same node (87 Ma). These differences also entail notable consequences on the preferred biogeographical hypothesis for the whole clade. Here we analyze a total of seven dating strategies by combining three calibration sources in independent BEAST runs to infer the most probable divergence timing for anole lizards (a mitochondrial rate for ND2 gene, the Anolis dominicanus fossil, and a group of fossils assigned to the Priscagamines, Iguanines, and Idontosaurus clades). Based on the estimated timing, we also addressed whether chronograms differ the most in deeper or shallower nodes by exploring the trend in the standard deviation of mean ages between chronograms across time. Next, we focus on the pattern for a single shallow node by hypothesizing the biogeography of the island-endemic Malpelo anole (Anolis agassizi), and evaluating the temporal congruence between the species' divergence and the island geology. The estimated set of ages suggests that anoles most likely diverged 72 Ma (71-73 Ma), with the crown group established around 58 Ma (51-65 Ma). Dispersal is therefore supported as the major driver in the biogeography of the group (and in Caribbean lineages in particular). Our analyses also indicated that (1) rate-based analyses pulled dates toward younger ages, (2) the differences in node ages between chronograms decrease towards the tips regardless of the position of the constrained node, and that (3) the estimated age for deep nodes (e.g. Anolis stem) is highly influenced when deep nodes are also constrained. The latter two results imply that the estimated age for shallower nodes is largely unaffected by the used temporal constraint. The congruence of all chronograms for the Malpelo anole also supports this finding. Anolis agassizi was found to have diverged before the emergence of Malpelo island in each analysis (anole: 19-31 Ma vs. Malpelo island: 16-17 Ma). Finally, we recommend when performing absolute dating analyses to first test for sequence saturation in the analyzed dataset (especially when calibrations are based on molecular rates). Our study also points out the importance of using multiple node constraints, especially when placed deeply in the tree, for fossil-based divergence dating analyses.}, } @article {pmid29906604, year = {2018}, author = {Sun, Y and Wong, E and Ahyong, ST and Williamson, JE and Hutchings, PA and Kupriyanova, EK}, title = {Barcoding and multi-locus phylogeography of the globally distributed calcareous tubeworm genus Hydroides Gunnerus, 1768 (Annelida, Polychaeta, Serpulidae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {732-745}, doi = {10.1016/j.ympev.2018.06.021}, pmid = {29906604}, issn = {1095-9513}, abstract = {Hydroides is a large and diverse group of calcareous tubeworms (Serpulidae, Annelida) recognised by a distinctive but variable two-tiered operculum. Despite considerable research using several species of Hydroides as models in ecological and biofouling studies, phylogenetic and biogeographic relationships within the genus are still poorly understood. Using combined mitochondrial (COI, cytochrome b) and nuclear (18S, 28S and ITS) gene markers for 284 individuals of 45 morphospecies of Hydroides, we investigated the global phylogenetic and biogeographic relationships within the genus. Phylogenetic topologies were well supported and indicated high genetic diversity within Hydroides, revealing potential cryptic species. Present results also include the first COI barcoding data enabling rapid and effective species identification of Hydroides on a global scale. Phylogenetic relationships within Hydroides were more concordant with geographical distributions than morphological similarity of their opercula. Molecular divergence estimates suggested the origin and subsequent diversification in the western Tethys Sea followed by a shift of the historical centre of diversity from the Indo-Mediterranean region to the central Indo-Pacific during the last 50 million years. Further studies on population genetics of species consisting of multiple lineages would provide a better understanding on the status of potential cryptic species. Furthermore, paleogeographic studies based on fossil Hydroides tubes would provide evidence to test this biogeographic hypothesis.}, } @article {pmid29906259, year = {2018}, author = {Lee, SD}, title = {Collimonas antrihumi sp. nov., isolated from a natural cave and emended description of the genus Collimonas.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2448-2453}, doi = {10.1099/ijsem.0.002855}, pmid = {29906259}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Caves/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Oxalobacteraceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel bacterium, designated strain C3-17T, was isolated from a natural cave in Jeju, Republic of Korea. Cells of the organism were Gram-stain-negative, strictly aerobic, non-sporulating, non-motile rods. The polar lipids present were phosphatidylethanolamine, phosphatidylglycerol, two unidentified aminophospholipids, an unidentified aminolipid and an unidentified lipid. The sole isoprenoid quinone was Q-8. The predominant fatty acids were C16 : 0 and summed feature 3, and the DNA G+C content was 54.5 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain C3-17T belonged to the family Oxalobacteraceae and was most closely related to the type strains of the genus Collimonas. 16S rRNA gene sequence similarities between the novel isolate and the closest neighbours, Collimonas pratensis Ter91T, Collimonas fungivorans Ter6T and Collimonas arenae NCCB 100031T were 98.7, 98.5 and 98.1 %, respectively. On the basis of data obtained by polyphasic analyses and DNA-DNA hybridization, strain C3-17T (=KACC 19055T=DSM 104040T) represents a novel species of the genus Collimonas, for which the name Collimonasantrihumi sp. nov. is proposed.}, } @article {pmid29906204, year = {2018}, author = {Vázquez-Laslop, N and Mankin, AS}, title = {Context-Specific Action of Ribosomal Antibiotics.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {185-207}, doi = {10.1146/annurev-micro-090817-062329}, pmid = {29906204}, issn = {1545-3251}, abstract = {The ribosome is a major antibiotic target. Many types of inhibitors can stop cells from growing by binding at functional centers of the ribosome and interfering with its ability to synthesize proteins. These antibiotics were usually viewed as general protein synthesis inhibitors, which indiscriminately stop translation at every codon of every mRNA, preventing the ribosome from making any protein. However, at each step of the translation cycle, the ribosome interacts with multiple ligands (mRNAs, tRNA substrates, translation factors, etc.), and as a result, the properties of the translation complex vary from codon to codon and from gene to gene. Therefore, rather than being indiscriminate inhibitors, many ribosomal antibiotics impact protein synthesis in a context-specific manner. This review presents a snapshot of the growing body of evidence that some, and possibly most, ribosome-targeting antibiotics manifest site specificity of action, which is modulated by the nature of the nascent protein, the mRNA, or the tRNAs.}, } @article {pmid29905874, year = {2018}, author = {Hoshino, Y and Gaucher, EA}, title = {On the origin of isoprenoid biosynthesis.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29905874}, issn = {1537-1719}, support = {R01 AR069137/AR/NIAMS NIH HHS/United States ; }, abstract = {Isoprenoids and their derivatives represent the largest group of organic compounds in nature and are distributed universally in the three domains of life. Isoprenoids are biosynthesized from isoprenyl diphosphate units, generated by two distinctive biosynthetic pathways: mevalonate pathway and methylerthritol 4-phosphate pathway. Archaea and eukaryotes exclusively have the former pathway, while most bacteria have the latter. Some bacteria, however, are known to possess the mevalonate pathway genes. Understanding the evolutionary history of these two isoprenoid biosynthesis pathways in each domain of life is critical since isoprenoids are so interweaved in the architecture of life that they would have had indispensable roles in the early evolution of life. Our study provides a detailed phylogenetic analysis of enzymes involved in the mevalonate pathway and sheds new light on its evolutionary history. The results suggest that a potential mevalonate pathway is present in the recently discovered superphylum Candidate Phyla Radiation (CPR), and further suggest a strong evolutionary relationship exists between archaea and CPR. Interestingly, CPR harbors the characteristics of both the bacterial-type and archaeal-type mevalonate pathways and may retain signatures regarding the ancestral isoprenoid biosynthesis pathway in the last universal common ancestor. Our study supports the ancient origin of the mevalonate pathway in the three domains of life as previously inferred, but concludes that the evolution of the mevalonate pathway was more complex.}, } @article {pmid29905872, year = {2018}, author = {Cury, J and Oliveira, PH and de la Cruz, F and Rocha, EPC}, title = {Host range and genetic plasticity explain the co-existence of integrative and extrachromosomal mobile genetic elements.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29905872}, issn = {1537-1719}, support = {281605//European Research Council/International ; }, abstract = {Self-transmissible mobile genetic elements drive horizontal gene transfer between prokaryotes. Some of these elements integrate in the chromosome, whereas others replicate autonomously as plasmids. Recent works showed the existence of few differences, and occasional interconversion, between the two types of elements. Here, we enquired on why evolutionary processes have maintained the two types of mobile genetic elements by comparing integrative and conjugative elements (ICE) with extrachromosomal ones (conjugative plasmids) of the highly abundant MPFT conjugative type. We observed that plasmids encode more replicases, partition systems, and antibiotic resistance genes, whereas ICEs encode more integrases and metabolism-associated genes. ICEs and plasmids have similar average sizes, but plasmids are much more variable, have more DNA repeats, and exchange genes more frequently. On the other hand, we found that ICEs are more frequently transferred between distant taxa. We propose a model where the different genetic plasticity and amplitude of host range between elements explain the co-occurrence of integrative and extra-chromosomal elements in microbial populations. In particular, the conversion from ICE to plasmid allows ICE to be more plastic, while the conversion from plasmid to ICE allows the expansion of the element's host range.}, } @article {pmid29905849, year = {2018}, author = {Tohmonda, T and Kamiya, A and Ishiguro, A and Iwaki, T and Fujimi, TJ and Hatayama, M and Aruga, J}, title = {Identification and characterization of novel conserved domains in metazoan Zic proteins.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy122}, pmid = {29905849}, issn = {1537-1719}, abstract = {Zic family genes encode C2H2-type zinc finger proteins that act as critical toolkit proteins in the metazoan body plan establishment. In this study, we searched evolutionarily conserved domains among 121 Zic protein sequences from 22 animal phyla and 40 classes, and addressed their evolutionary significance. The collected sequences included those from poriferans and orthonectids. We discovered seven new conserved domains (CDs), CD0-CD6, (in order from the N- to C-terminus) using the most conserved Zic protein sequences from Deuterostomia (Hemichordata, Cephalochordata), Lophotrochozoa (Cephalopoda and Brachiopoda), and Ecdysozoa (Chelicerata, Priapulida). Subsequently, we analyzed the evolutionary history of Zic CDs including the known CDs (ZOC, ZFD, ZFNC, and ZFCC). All Zic CDs are predicted to have existed in a bilaterian ancestor. During evolution, they have degenerated in a taxa-selective manner with significant correlations among CDs. The N terminal CD (CD0) was largely lost, but was observed in Brachiopoda, Priapulida, Hemichordata, Echinodermata, and Cephalochordata, and the C terminal CD (CD6) was highly conserved in conserved-type-Zic possessing taxa, but was truncated in vertebrate Zic gene paralogues (Zic1/2/3), generating a vertebrate-specific C-terminus critical for transcriptional regulation. ZOC was preferentially conserved in insects and in an anthozoan paralogue, and it was bound to the homeodomain transcription factor Msx in a phylogenetically conserved manner. Accordingly, the extent of divergence of Msx and Zic CDs from their respective bilaterian ancestors is strongly correlated. These results suggest that coordinated divergence among the toolkit CDs and among toolkit proteins is involved in the divergence of metazoan body plans.}, } @article {pmid29905791, year = {2018}, author = {Merlino, G and Barozzi, A and Michoud, G and Ngugi, DK and Daffonchio, D}, title = {Microbial ecology of deep-sea hypersaline anoxic basins.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy085}, pmid = {29905791}, issn = {1574-6941}, abstract = {Deep hypersaline anoxic basins (DHABs) are unique water bodies occurring within fractures at the bottom of the sea, where the dissolution of anciently buried evaporites created dense anoxic brines that are separated by a chemocline/pycnocline from the overlying oxygenated deep-seawater column. DHABs have been described in the Gulf of Mexico, the Mediterranean Sea, the Black Sea and the Red Sea. They are characterized by prolonged historical separation of the brines from the upper water column due to lack of mixing and by extreme conditions of salinity, anoxia, and relatively high hydrostatic pressure and temperatures. Due to these combined selection factors, unique microbial assemblages thrive in these polyextreme ecosystems. The topological localization of the different taxa in the brine-seawater transition zone coupled with the metabolic interactions and niche adaptations determine the metabolic functioning and biogeochemistry of DHABs. In particular, inherent metabolic strategies accompanied by genetic adaptations have provided insights on how prokaryotic communities can adapt to salt-saturated conditions. Here, we review the current knowledge of the diversity, genomics, metabolisms and ecology of prokaryotes in DHABs.}, } @article {pmid29905781, year = {2018}, author = {Puntieri, F and Andrioli, NB and Nieves, M}, title = {Association between Genomic Instability and Evolutionary Chromosomal Rearrangements in Neotropical Primates.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1647-1656}, doi = {10.1093/gbe/evy119}, pmid = {29905781}, issn = {1759-6653}, mesh = {Alouatta/*genetics ; Animals ; Atelinae/*genetics ; Cebus/*genetics ; Chromosome Breakage ; Chromosomes/genetics ; *Evolution, Molecular ; Female ; *Gene Rearrangement ; *Genomic Instability ; Male ; *Sister Chromatid Exchange ; }, abstract = {During the last decades, the mammalian genome has been proposed to have regions prone to breakage and reorganization concentrated in certain chromosomal bands that seem to correspond to evolutionary breakpoints. These bands are likely to be involved in chromosome fragility or instability. In Primates, some biomarkers of genetic damage may be associated with various degrees of genomic instability. Here, we investigated the usefulness of Sister Chromatid Exchange as a biomarker of potential sites of frequent chromosome breakage and rearrangement in Alouatta caraya, Ateles chamek, Ateles paniscus, and Cebus cay. These Neotropical species have particular genomic and chromosomal features allowing the analysis of genomic instability for comparative purposes. We determined the frequency of spontaneous induction of Sister Chromatid Exchanges and assessed the relationship between these and structural rearrangements implicated in the evolution of the primates of interest. Overall, A. caraya and C. cay presented a low proportion of statistically significant unstable bands, suggesting fairly stable genomes and the existence of some kind of protection against endogenous damage. In contrast, Ateles showed a highly significant proportion of unstable bands; these were mainly found in the rearranged regions, which is consistent with the numerous genomic reorganizations that might have occurred during the evolution of this genus.}, } @article {pmid29904995, year = {2018}, author = {Karagic, N and Härer, A and Meyer, A and Torres-Dowdall, J}, title = {Heterochronic opsin expression due to early light deprivation results in drastically shifted visual sensitivity in a cichlid fish: Possible role of thyroid hormone signaling.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {4}, pages = {202-214}, doi = {10.1002/jez.b.22806}, pmid = {29904995}, issn = {1552-5015}, abstract = {During early ontogeny, visual opsin gene expression in cichlids is influenced by prevailing light regimen. Red light, for example, leads to an early switch from the expression of short-wavelength sensitive to long-wavelength sensitive opsins. Here, we address the influence of light deprivation on opsin expression. Individuals reared in constant darkness during the first 14 days post-hatching (dph) showed a general developmental delay compared with fish reared under a 12:12 hr light-dark cycle (control group). Several characters including pigmentation patterns and eye development, appeared later in dark-reared individuals. Quantitative real-time PCR and fluorescent in situ hybridization at six time points during the 14 days period revealed that fish from the control group expressed opsin genes from 5 dph on and maintained a short-wavelength sensitive phenotype (sws1, rh2b, and rh2a). Onset of opsin expression in dark-reared Midas cichlids was delayed by 4 days and visual sensitivity rapidly progressed toward a long-wavelength sensitive phenotype (sws2b, rh2a, and lws). Shifts in visual sensitivities toward longer wavelengths are mediated by thyroid hormone (TH) in many vertebrates. Compared to control fish, dark-reared individuals showed elevated dio3 expression levels - a validated proxy for TH concentration - suggesting higher circulating TH levels. Despite decelerated overall development, ontogeny of opsin gene expression was accelerated, resulting in retinae with long-wavelength shifted predicted sensitivities compared to light-reared individuals. Indirect evidence suggests that this was due to altered TH metabolism.}, } @article {pmid29904987, year = {2018}, author = {Stilwell, P and Lowe, C and Buckling, A}, title = {The effect of cheats on siderophore diversity in Pseudomonas aeruginosa.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1330-1339}, pmid = {29904987}, issn = {1420-9101}, support = {//Royal Society/ ; BB/K003240/2//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/K003240/1//BBSRC/ ; //NERC/ ; //AXA Research Fund/ ; }, abstract = {Cooperation can be maintained if cooperative behaviours are preferentially directed towards other cooperative individuals. Tag-based cooperation (greenbeards) - where cooperation benefits individuals with the same tag as the actor - is one way to achieve this. Tag-based cooperation can be exploited by individuals who maintain the specific tag but do not cooperate, and selection to escape this exploitation can result in the evolution of tag diversity. We tested key predictions crucial for the evolution of cheat-mediated tag diversity using the production of iron-scavenging pyoverdine by the opportunistic pathogen, Pseduomonas aeruginosa as a model system. Using two strains that produce different pyoverdine types and their respective cheats, we show that cheats outcompete their homologous pyoverdine producer, but are outcompeted by the heterologous producer in well-mixed environments. As a consequence, co-inoculating two types of pyoverdine producer and one type of pyoverdine cheat resulted in the pyoverdine type whose cheat was not present having a large fitness advantage. Theory suggests that in such interactions, cheats can maintain tag diversity in spatially structured environments, but that tag-based cooperation will be lost in well-mixed populations, regardless of tag diversity. We saw that when all pyoverdine producers and cheats were co-inoculated in well-mixed environments, both types of pyoverdine producers were outcompeted, whereas spatial structure (agar plates and compost microcosms), rather than maintaining diversity, resulted in the domination of one pyoverdine producer. These results suggest cheats may play a more limited role in the evolution of pyoverdine diversity than predicted.}, } @article {pmid29904977, year = {2018}, author = {Durmaz, E and Benson, C and Kapun, M and Schmidt, P and Flatt, T}, title = {An inversion supergene in Drosophila underpins latitudinal clines in survival traits.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1354-1364}, pmid = {29904977}, issn = {1420-9101}, support = {NSF DEB 0921307//National Science Foundation (NSF)/ ; 310030E-164207//Swiss National Science Foundation (SNSF)/ ; PP00P3_133641//Swiss National Science Foundation (SNSF)/ ; PP00P3_165836//Swiss National Science Foundation (SNSF)/ ; R01GM100366//National Institutes of Health (NIH)/ ; R01 GM100366/GM/NIGMS NIH HHS/United States ; }, abstract = {Chromosomal inversions often contribute to local adaptation across latitudinal clines, but the underlying selective mechanisms remain poorly understood. We and others have previously shown that a clinal inversion polymorphism in Drosophila melanogaster, In(3R)Payne, underpins body size clines along the North American and Australian east coasts. Here, we ask whether this polymorphism also contributes to clinal variation in other fitness-related traits, namely survival traits (lifespan, survival upon starvation and survival upon cold shock). We generated homokaryon lines, either carrying the inverted or standard chromosomal arrangement, isolated from populations approximating the endpoints of the North American cline (Florida, Maine) and phenotyped the flies at two growth temperatures (18 °C, 25 °C). Across both temperatures, high-latitude flies from Maine lived longer and were more stress resistant than low-latitude flies from Florida, as previously observed. Interestingly, we find that this latitudinal pattern is partly explained by the clinal distribution of the In(3R)P polymorphism, which is at ~ 50% frequency in Florida but absent in Maine: inverted karyotypes tended to be shorter-lived and less stress resistant than uninverted karyotypes. We also detected an interaction between karyotype and temperature on survival traits. As In(3R)P influences body size and multiple survival traits, it can be viewed as a 'supergene', a cluster of tightly linked loci affecting multiple complex phenotypes. We conjecture that the inversion cline is maintained by fitness trade-offs and balancing selection across geography; elucidating the mechanisms whereby this inversion affects alternative, locally adapted phenotypes across the cline is an important task for future work.}, } @article {pmid29904973, year = {2018}, author = {Harano, T and Kutsukake, N}, title = {Directional selection in the evolution of elongated upper canines in clouded leopards and sabre-toothed cats.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1268-1283}, doi = {10.1111/jeb.13309}, pmid = {29904973}, issn = {1420-9101}, support = {25711025//MEXT/ ; //ESB Cooperation Program, SOKENDAI/ ; }, abstract = {Extremely developed or specialized traits such as the elongated upper canines of extinct sabre-toothed cats are often not analogous to those of any extant species, which limits our understanding of their evolutionary cause. However, an extant species may have undergone directional selection for a similar extreme phenotype. Among living felids, the clouded leopard, Neofelis nebulosa, has exceptionally long upper canines for its body size. We hypothesized that directional selection generated the elongated upper canines of clouded leopards in a manner similar to the process in extinct sabre-toothed cats. To test this, we developed an approach that compared the effect of directional selection among lineages in a phylogeny using a simulation of trait evolution and approximate Bayesian computation. This approach was applied to analyse the evolution of upper canine length in the Felidae phylogeny. Our analyses consistently showed directional selection favouring longer upper canines in the clouded leopard lineage and a lineage leading to the sabre-toothed cat with the longest upper canines, Smilodon. Most of our analyses detected an effect of directional selection for longer upper canines in the lineage leading to another sabre-toothed cat, Homotherium, although this selection may have occurred exclusively in the primitive species. In all the analyses, the clouded leopard and Smilodon lineages showed comparable directional selection. This implies that clouded leopards share a selection advantage with sabre-toothed cats in having elongated upper canines.}, } @article {pmid29904961, year = {2018}, author = {Rodrigues, AMM}, title = {Demography, life history and the evolution of age-dependent social behaviour.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1340-1353}, doi = {10.1111/jeb.13308}, pmid = {29904961}, issn = {1420-9101}, abstract = {Since the inception of modern social evolution theory, a vast majority of studies have sought to explain cooperation using relatedness-driven hypotheses. Natural populations, however, show a substantial amount of variation in social behaviour that is uncorrelated with relatedness. Age offers a major alternative explanation for variation in behaviour that remains unaccounted for. Most natural populations are structured into age-classes, with ageing being a nearly universal feature of most major taxa, including eukaryotic and prokaryotic organisms. Despite this, the theoretical underpinnings of age-dependent social behaviour remain limited. Here, I investigate how group age-composition, demography and life history shape trajectories of age-dependent behaviours that are expressed conditionally on an actor and recipient's age. I show that demography introduces novel age-dependent selective pressures acting on social phenotypes. Furthermore, I find that life history traits influence the costs and benefits of cooperation directly, but also indirectly. Life history has a strong impact not only on the genetic structure of the population but also on the distribution of group age-compositions, with both of these processes influencing the expression of age-dependent cooperation. Age of peak reproductive performance, in particular, is of chief importance for the evolution of cooperation, as this will largely determine the age and relatedness of social partners. Moreover, my results suggest that later-life reproductive senescence may occur because of demographic effects alone, which opens new vistas on the evolution of menopause and related phenomena.}, } @article {pmid29904956, year = {2018}, author = {Tammaru, T and Johansson, NR and Õunap, E and Davis, RB}, title = {Day-flying moths are smaller: evidence for ecological costs of being large.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1400-1404}, doi = {10.1111/jeb.13306}, pmid = {29904956}, issn = {1420-9101}, support = {IUT20-33//Estonian Ministry of Education and Research/ ; }, abstract = {Research on evolutionary forces determining optimal body sizes has primarily relied on experimental evaluation of respective selective pressures. Accounting for among-species variation through application of phylogenetic comparative methods is a complementary although little used approach. It enables the direct association of body size values with particular environments. Using phylogenetically explicit comparative analyses, we show that small body size is associated with diurnal (rather than nocturnal) activity of adults among temperate species of the moth family Geometridae. The association of an exclusively adult trait with species-specific body size suggests that optimal body sizes are at least partly determined by the costs being a large adult, as opposed to the more frequently considered costs of attaining large size. It appears likely that size-selective predation by insectivorous birds is the primary factor responsible for selection against large body size in day-flying moths.}, } @article {pmid29904566, year = {2018}, author = {Fisher, GR and Olimpo, JT and McCabe, TM and Pevey, RS}, title = {The Tigriopus CURE - A Course-Based Undergraduate Research Experience with Concomitant Supplemental Instruction.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904566}, issn = {1935-7877}, abstract = {Evidence indicates that students who participate in scientific research during their undergraduate experience are more likely to pursue careers in the STEM disciplines and to develop increased scientific reasoning and literacy skills. One avenue to increase student engagement in research is via their enrollment in course-based undergraduate research experiences (CUREs), where they are able to conduct authentic research as part of the laboratory curriculum. The information presented herein provides an example of a CURE which was developed and implemented in an introductory cell and molecular biology course at the University of Northern Colorado. In addition to describing the Tigriopus CURE curriculum itself, we also present evidence regarding the effectiveness of the CURE in promoting students' development of confidence in science process skills, quantitative reasoning skills, and written communication skills. The curricular details of the Tigriopus CURE are provided in this article to provide instructors who are interested in CUREs the opportunity to implement this specific CURE in their own course.}, } @article {pmid29904565, year = {2018}, author = {Wolyniak, MJ and Reyna, NS and Plymale, R and Pope, WH and Westholm, DE}, title = {Mass Spectrometry as a Tool to Enhance "-omics" Education.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904565}, issn = {1935-7877}, support = {P20 GM103429/GM/NIGMS NIH HHS/United States ; P20 RR016460/RR/NCRR NIH HHS/United States ; }, } @article {pmid29904564, year = {2018}, author = {Mangan, DF and Cloyd, ET and Romo, JA and Wessner, DR and Westenberg, DJ and Adukwu, E and Menninger, H and Gardy, J}, title = {Introducing the JMBE Themed Issue on Science Communication.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, doi = {10.1128/jmbe.v19i1.1601}, pmid = {29904564}, issn = {1935-7877}, } @article {pmid29904563, year = {2018}, author = {Smith, M and Segura-Totten, M and West, K}, title = {QR Code Lecture Activity as a Tool for Increasing Nonmajors Biology Students' Enjoyment of Interaction with Their Local Environment.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904563}, issn = {1935-7877}, abstract = {The impact of the Internet on education has been recognized for decades, and as technology advances, the ways in which students can access Internet content is ever increasing. Most students have some kind of portable smart device with which they access Internet content without the locational constraints of a desktop computer. This mobility has prompted abundant literature suggesting ways that Quick Response Codes (QR codes), a kind of two dimensional barcode, could be used to advance student learning. However, very few studies have tested the usefulness of QR codes in undergraduate science classes. We report on our development of a campus "scavenger hunt" activity using QR codes. We found that this activity develops application skills of the concepts of native and invasive species and enjoyment of coverage of content relative to traditional lecture in a nonmajors Environmental Science class at a four-year teaching institution.}, } @article {pmid29904562, year = {2018}, author = {Segarra, VA and Natalizio, B and Falkenberg, CV and Pulford, S and Holmes, RM}, title = {STEAM: Using the Arts to Train Well-Rounded and Creative Scientists.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904562}, issn = {1935-7877}, abstract = {While the demand for a strong STEM workforce continues to grow, there are challenges that threaten our ability to recruit, train, and retain such a workforce in a way that is effective and sustainable and fosters innovation. One way in which we are meeting this challenge is through the use of the arts in the training of scientists. In this Perspectives article, we review the use of the arts in science education and its benefits in both K-12 and postsecondary education. We also review the use of STEAM (science, technology, engineering, arts, and mathematics) programs in science outreach and the development of professional scientists.}, } @article {pmid29904560, year = {2018}, author = {Barr, R and Davis, MF}, title = {Reproducing Clinically Significant Multi-Organism Cultures to Improve Clinical Microbiology Education and Practice.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904560}, issn = {1935-7877}, } @article {pmid29904559, year = {2018}, author = {McOwat, K and Stanley-Wall, NR}, title = {Biofilm Building: A Simple Board Game to Reinforce Knowledge of Biofilm Formation.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904559}, issn = {1935-7877}, } @article {pmid29904558, year = {2018}, author = {Clawson, ED and Blair, V and Nepper, JF and Stilwell, MD and Tangen, T and Weibel, DB}, title = {Laboratory Activity Using Accessible Microfluidics to Study Nematode Behavior in an Electrical Field.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904558}, issn = {1935-7877}, support = {T32 GM008293/GM/NIGMS NIH HHS/United States ; }, } @article {pmid29904557, year = {2018}, author = {Segarra, VA and Tillery, M}, title = {Key Concepts in Developmental Psychology and Science Pedagogy Help Undergraduates in High School Science Outreach.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904557}, issn = {1935-7877}, } @article {pmid29904556, year = {2018}, author = {Jandu, N}, title = {Clicker Student Response Systems: Dedicated Physical Devices or Web-Enabled Systems that Allow Student to Bring Their Own Device (BYOD).}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904556}, issn = {1935-7877}, } @article {pmid29904555, year = {2018}, author = {Goudsouzian, LK}, title = {Hollywood-Style Movie Trailers Increase Student Interest.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904555}, issn = {1935-7877}, } @article {pmid29904554, year = {2018}, author = {Olimpo, JT and Rodriguez, R and Lougheed, VL and Tweedie, CE}, title = {CUREcasts: An Innovative Mechanism to Increase Communication of Scientific Outcomes to Novice and Expert Audiences within the Context of Course-Based Undergraduate Research Experiences.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904554}, issn = {1935-7877}, } @article {pmid29904553, year = {2018}, author = {Hoskins, SG and Gottesman, AJ}, title = {Investigating Undergraduates' Perceptions of Science in Courses Taught Using the CREATE Strategy.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904553}, issn = {1935-7877}, abstract = {Many science educators agree that 21st century students need to develop mature scientific thinking skills. Unsurprisingly, students' and experts' perceptions about the nature of scientific knowledge differ. Moreover, students' naïve and entrenched epistemologies can preclude their development toward "thinking like scientists." Novel teaching approaches that guide students toward more mature perceptions may be needed to support their development of scientific thinking skills. To address such issues, physics educators developed the Colorado Learning Attitudes About Science Survey (CLASS), subsequently adapted for chemistry and biology. These surveys are "designed to compare novice and expert perceptions about the content and structure of a specific discipline; the source of knowledge about that discipline, including connection of the discipline to the real world; and problem-solving approaches" (Semsar et al., CBE Life Sci. Educ. 10:268-278; p 269). We used CLASS-Bio to track students' perceptions of science in separate first-year and upper-level CREATE (Consider, Read, Elucidate hypotheses, Analyze and interpret the data, Think of the next Experiment) electives, hypothesizing that perceptions would become significantly more expert-like across a semester. Both first-year and upper-level cohorts made significant expert-like shifts. Students also made significant critical thinking gains in CREATE courses. Our findings of more mature, expert-like perceptions of science post-course contrast with those of previous studies, where students' thinking became significantly less expert-like across a term of introductory instruction and changed little in upper-level biology electives. Augmenting traditional biology curricula with CREATE courses could be an economical way to help undergraduates develop more mature views of science.}, } @article {pmid29904552, year = {2018}, author = {Norman-McKay, L and , }, title = {Microbiology in Nursing and Allied Health (MINAH) Undergraduate Curriculum Guidelines: A Call to Retain Microbiology Lecture and Laboratory Courses in Nursing and Allied Health Programs.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904552}, issn = {1935-7877}, abstract = {This position paper presents the Microbiology in Nursing and Allied Health (MINAH) Undergraduate Curriculum Guidelines (Appendix 1) that were developed by a committee effort of the American Society for Microbiology (ASM). These guidelines differ from the 2012 General Microbiology Undergraduate Curriculum Guidelines presented by a separate ASM taskforce. The fact that some U.S. nursing programs are eliminating microbiology courses from their curriculum prompted the development of curriculum guidelines focused on nursing and allied health. Here we review: 1) factors that have shifted microbiology's place in health professions curricula (with a focus on nursing associate degree programs); 2) resources to support microbiology's inclusion in nursing and allied health programs; and 3) recommendations for maintaining microbiology as a full course (lecture and laboratory) in nursing and allied health undergraduate curricula.}, } @article {pmid29904551, year = {2018}, author = {Dang, NV and Chiang, JC and Brown, HM and McDonald, KK}, title = {Curricular Activities that Promote Metacognitive Skills Impact Lower-Performing Students in an Introductory Biology Course.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904551}, issn = {1935-7877}, abstract = {This study explores the impacts of repeated curricular activities designed to promote metacognitive skills development and academic achievement on students in an introductory biology course. Prior to this study, the course curriculum was enhanced with pre-assignments containing comprehension monitoring and self-evaluation questions, exam review assignments with reflective questions related to study habits, and an optional opportunity for students to explore metacognition and deep versus surface learning. We used a mixed-methods study design and collected data over two semesters. Self-evaluation, a component of metacognition, was measured via exam score postdictions, in which students estimated their exam scores after completing their exam. Metacognitive awareness was assessed using the Metacognitive Awareness Inventory (MAI) and a reflective essay designed to gauge students' perceptions of their metacognitive skills and study habits. In both semesters, more students over-predicted their Exam 1 scores than under-predicted, and statistical tests revealed significantly lower mean exam scores for the over-predictors. By Exam 3, under-predictors still scored significantly higher on the exam, but they outnumbered the over-predictors. Lower-performing students also displayed a significant increase in exam postdiction accuracy by Exam 3. While there was no significant difference in students' MAI scores from the beginning to the end of the semester, qualitative analysis of reflective essays indicated that students benefitted from the assignments and could articulate clear action plans to improve their learning and performance. Our findings suggest that assignments designed to promote metacognition can have an impact on students over the course of one semester and may provide the greatest benefits to lower-performing students.}, } @article {pmid29904550, year = {2018}, author = {Majocha, M and Davenport, Z and Braun, DC and Gormally, C}, title = {"Everyone Was Nice…But I Was Still Left Out": An Interview Study About Deaf Interns' Research Experiences in STEM.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904550}, issn = {1935-7877}, abstract = {Science, technology, engineering, and mathematics (STEM) undergraduate research experiences improve success, persistence, and promote a feeling of belonging to a community. Like their hearing peers, deaf STEM majors often participate in undergraduate research experiences. However, deaf students typically interact with hearing faculty lacking experience with deaf students and awareness of Deaf culture, which unintentionally impacts their research experiences. This interview study sought to understand deaf students' research experiences and their relationships with hearing mentors. Findings indicate that lack of awareness of Deaf culture and lack of communication access impact students' experiences. We make recommendations on improving deaf students' research experiences.}, } @article {pmid29904549, year = {2018}, author = {Olimpo, JT and Pevey, RS and McCabe, TM}, title = {Incorporating an Interactive Statistics Workshop into an Introductory Biology Course-Based Undergraduate Research Experience (CURE) Enhances Students' Statistical Reasoning and Quantitative Literacy Skills.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904549}, issn = {1935-7877}, abstract = {Course-based undergraduate research experiences (CUREs) provide an avenue for student participation in authentic scientific opportunities. Within the context of such coursework, students are often expected to collect, analyze, and evaluate data obtained from their own investigations. Yet, limited research has been conducted that examines mechanisms for supporting students in these endeavors. In this article, we discuss the development and evaluation of an interactive statistics workshop that was expressly designed to provide students with an open platform for graduate teaching assistant (GTA)-mentored data processing, statistical testing, and synthesis of their own research findings. Mixed methods analyses of pre/post-intervention survey data indicated a statistically significant increase in students' reasoning and quantitative literacy abilities in the domain, as well as enhancement of student self-reported confidence in and knowledge of the application of various statistical metrics to real-world contexts. Collectively, these data reify an important role for scaffolded instruction in statistics in preparing emergent scientists to be data-savvy researchers in a globally expansive STEM workforce.}, } @article {pmid29904548, year = {2018}, author = {Tetro, JA}, title = {Learning from History to Increase Positive Public Reception and Social Value Alignment of Evidence-Based Science Communication.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904548}, issn = {1935-7877}, abstract = {For effective science communication, three general objectives should be taken into consideration: 1) accurate conveyance of the scientific evidence; 2) warm public reception of the communicator; and 3) alignment of the information with social values. An examination of both successful and failed science communication efforts over the course of history can reveal strategies to better meet these objectives. This article looks back at influential moments of science communication over the past two millennia in the context of the objectives and, using lessons learned from these events as a guide, introduces a five-element approach to improve the potential for attaining the objectives.}, } @article {pmid29904547, year = {2018}, author = {Durán, C and Blanco, V and Piccini, C and Zunino, P and Rodríguez, E}, title = {A Simple and Effective Method for Extracting Potential Mutagens from Sediment Samples in the Classroom Laboratory Setting.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904547}, issn = {1935-7877}, } @article {pmid29904546, year = {2018}, author = {Kampschulte, L and Akaygün, S and Adadan, E and Eilert, K and Heyduck, B}, title = {Interdisciplinary Research Brought to School-Connecting Chemistry and Biology through Nanotechnology.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904546}, issn = {1935-7877}, } @article {pmid29904545, year = {2018}, author = {Mangan, DF}, title = {The Head and Heart of Science Communication Sage Advice from Alan Alda.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, doi = {10.1128/jmbe.v19i1.1425}, pmid = {29904545}, issn = {1935-7877}, } @article {pmid29904544, year = {2018}, author = {Smith-Keiling, BL and Swanson, LK and Dehnbostel, JM}, title = {Interventions for Supporting and Assessing Science Writing Communication: Cases of Asian English Language Learners.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904544}, issn = {1935-7877}, abstract = {In seeking to support diversity, one challenge lies in adequately supporting and assessing science cognitions in a writing-intensive Biochemistry laboratory course when highly engaged Asian English language learners (Asian ELLs) struggle to communicate and make novice errors in English. Because they may understand advanced science concepts, but are not being adequately assessed for their deeper scientific understanding, we sought and examined interventions. We hypothesized that inquiry strategies, scaffolded learning through peer evaluation, and individualized tools that build writing communication skills would increase confidence. To assess scientific thinking, Linguistic Inquiry Word Count (LIWC) software measured underlying analytic and cognitive features of writing despite grammatical errors. To determine whether interventions improved student experience or learning outcomes, we investigated a cross-sectional sample of cases within experimental groups (n = 19) using a mixed-methods approach. Overall trends of paired t-tests from Asian ELLs' pre/post surveys showed gains in six measures of writing confidence, with some statistically significant gains in confidence in writing skill (p=0.025) and in theory (p≤0.05). LIWC scores for Asian ELL and native-English-speaking students were comparable except for increased cognitive scores for Asian ELLs and detectable individual differences. An increase in Asian ELLs' cognitive scores in spring/summer over fall was observed (p = 0.04), likely as a result of greater cognitive processes with language use, inquiry-related interventions, and peer evaluation. Individual cases further elucidated challenges faced by Asian ELL students. LIWC scores of student writing may be useful in determining underlying understanding. Interventions designed to provide support and strengthen the writing of Asian ELL students may also improve their confidence in writing, even if improvement is gradual.}, } @article {pmid29904543, year = {2018}, author = {Beason-Abmayr, B and Wilson, JS}, title = {Building a Partnership with a Campus Communication Center.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904543}, issn = {1935-7877}, abstract = {Although abundant evidence in STEM education literature emphasizes the incorporation of both primary literature analysis and communication of science into the undergraduate classroom, biology educators are rarely given the necessary support to teach students how to present scientific data from primary literature. Consequently, students often receive limited training in this valuable skill. We report on a collaboration between a biosciences instructor and communication center director who together designed a workshop to teach undergraduate students in a laboratory course to present material from primary literature sources. The workshop taught content selection, slide design, and oral delivery skills using authentic, content-based materials and student models. Following the introduction of this workshop into the course, student performance on the presentations, including their apparent understanding of scientific concepts, improved noticeably. Establishing partnerships such as this one can improve the efforts of biology educators to teach effective science communication to our students.}, } @article {pmid29904542, year = {2018}, author = {Taylor, C and Dewsbury, BM}, title = {On the Problem and Promise of Metaphor Use in Science and Science Communication.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904542}, issn = {1935-7877}, abstract = {The language of science is largely metaphorical. Scientists rely on metaphor and analogy to make sense of scientific phenomena and communicate their findings to each other and to the public. Yet, despite their utility, metaphors can also constrain scientific reasoning, contribute to public misunderstandings, and, at times, inadvertently reinforce stereotypes and messages that undermine the goals of inclusive science. This paper 1) examines the generative potential of metaphors to the advancement of scientific knowledge and science communication, 2) highlights the ways in which outdated metaphors may limit scientific inquiry and contribute to public misunderstandings, and 3) critically analyzes the implications of cryptic social and political messages embedded in common metaphors in the life sciences.}, } @article {pmid29904541, year = {2018}, author = {de Fraga, FBFF}, title = {Towards an Evolutionary Perspective in Teaching and Popularizing Microbiology.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904541}, issn = {1935-7877}, abstract = {Microorganisms are extremely abundant on our planet, and, as a result, they interact with many others forms of life. Today, science recognizes the essential role of these organisms in the emergence and maintenance of life on Earth. Nonetheless, misconceptions about microorganisms in the imaginations of students and the lay audience persist. A major challenge in teaching and popularizing microbiology is to provide students and the general public with a varied understanding of microbes in nature to reinforce their importance in a multitude of processes. In this perspective article, I discuss the persistence of the association between microbes and disease in laypersons' views. Moreover, I advocate for the adoption of a perspective anchored in evolutionary biology for teaching and popularizing microbiology to minimize this problem. To do so, I present several topics that interconnect evolution and microbiology and discuss how these topics could increase the general public's understanding of the microbial world.}, } @article {pmid29904540, year = {2018}, author = {Irizarry-Barreto, P and Coletta, S and Scott, K}, title = {Using a Mobile Laboratory to Promote College-Level Outreach and Graduate Student Engagement in Precollege STEM Literacy.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904540}, issn = {1935-7877}, abstract = {This article presents a case study about the impact that our mobile laboratory, the Rutgers Science Explorer bus, has had on the professional development of graduate students and content enrichment for the middle school communities in the state of New Jersey.}, } @article {pmid29904539, year = {2018}, author = {Aune, JE and Evans, LL and Boury, N}, title = {Using Nonfiction Narratives in an English Course to Teach the Nature of Science and Its Importance to Communicating About Science.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904539}, issn = {1935-7877}, abstract = {The nature of science (NOS) is a foundational framework for understanding scientific ideas and concepts. This framework includes scientific methodology, the process of revising and interpreting data, and the ways in which science is a social endeavor. Nature of science literature treats science as a way of knowing that is based on observable phenomenon. While discipline-specific coursework teaches the factual information of science, it may fall short on teaching scientific literacy, a key component of which is understanding NOS. We have designed an English course that features nonfiction narratives describing the early days of epidemiology, hygiene awareness, and the current controversy surrounding vaccination. Using a validated assessment of student understanding of NOS, the Student Understanding of Science and Scientific Inquiry (SUSSI), we have determined that this science-themed English composition course was effective in teaching NOS. Student understanding of NOS increased between the beginning and the end of the course in eight of the nine parameters of NOS measured, with the greatest gains in understanding the role of revision and of creativity in science. Our data imply that the course helped students develop a slightly less naïve understanding of the nature of science and its importance in the development and dissemination of scientific ideas and concepts.}, } @article {pmid29904538, year = {2018}, author = {Bankston, A and McDowell, GS}, title = {Changing the Culture of Science Communication Training for Junior Scientists.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904538}, issn = {1935-7877}, abstract = {Being successful in an academic environment places many demands on junior scientists. Science communication currently may not be adequately valued and rewarded, and yet communication to multiple audiences is critical for ensuring that it remains a priority in today's society. Due to the potential for science communication to produce better scientists, facilitate scientific progress, and influence decision-making at multiple levels, training junior scientists in both effective and ethical science communication practices is imperative, and can benefit scientists regardless of their chosen career path. However, many challenges exist in addressing specific aspects of this training. Principally, science communication training and resources should be made readily available to junior scientists at institutions, and there is a need to scale up existing science communication training programs and standardize core aspects of these programs across universities, while also allowing for experimentation with training. We propose a comprehensive core training program be adopted by universities, utilizing a centralized online resource with science communication information from multiple stakeholders. In addition, the culture of science must shift toward greater acceptance of science communication as an essential part of training. For this purpose, the science communication field itself needs to be developed, researched and better understood at multiple levels. Ultimately, this may result in a larger cultural change toward acceptance of professional development activities as valuable for training scientists.}, } @article {pmid29904537, year = {2018}, author = {Hall, SE and Birch, C}, title = {Creating Successful Campus Partnerships for Teaching Communication in Biology Courses and Labs.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904537}, issn = {1935-7877}, abstract = {Creating and teaching successful writing and communication assignments for biology undergraduate students can be challenging for faculty trying to balance the teaching of technical content. The growing body of published research and scholarship on effective teaching of writing and communication in biology can help inform such work, but there are also local resources available to support writing within biology courses that may be unfamiliar to science faculty and instructors. In this article, we discuss common on-campus resources biology faculty can make use of when incorporating writing and communication into their teaching. We present the missions, histories, and potential collaboration outcomes of three major on-campus writing resources: writing across the curriculum and writing in the disciplines initiatives (WAC/WID), writing programs, and writing centers. We explain some of the common misconceptions about these resources in order to help biology faculty understand their uses and limits, and we offer guiding questions faculty might ask the directors of these resources to start productive conversations. Collaboration with these resources will likely save faculty time and effort on curriculum development and, more importantly, will help biology students develop and improve their critical reading, writing, and communication skills.}, } @article {pmid29904536, year = {2018}, author = {Parker, CT and Cockerham, D and Foss, AW}, title = {Communicating Climate Change: Lessons Learned from a Researcher-Museum Collaboration.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904536}, issn = {1935-7877}, abstract = {The need for science education and outreach is great. However, despite the ever-growing body of available scientific information, facts are often misrepresented to or misunderstood by the general public. This can result in uninformed decisions that negatively impact society at both individual and community levels. One solution to this problem is to make scientific information more available to the public through outreach programs. Most outreach programs, however, focus on health initiatives, STEM programs, or young audiences exclusively. This article describes a collaboration between the Research and Learning Center at the Fort Worth Museum of Science and History and an interdisciplinary team of researchers from the Dallas-Fort Worth (DFW) metroplex area. The collaboration was a pilot effort of a science communication fellowship and was designed to train researchers to effectively convey current science information to the public with a focus on lifelong learning. We focus on the broader idea of a university-museum collaboration that bridges the science communication gap as we outline the process of forming this collaboration, lessons we learned from the process, and directions that can support future collaborations.}, } @article {pmid29904535, year = {2018}, author = {Rowland, S and Hardy, J and Colthorpe, K and Pedwell, R and Kuchel, L}, title = {CLIPS (Communication Learning in Practice for Scientists): A New Online Resource Leverages Assessment to Help Students and Academics Improve Science Communication.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904535}, issn = {1935-7877}, abstract = {The ability to communicate is a crucial graduate outcome for science students; however, crowded curricula and large class sizes make it difficult to find time to explicitly teach foundational communication skills. In response to these challenges, we developed an online resource called Communication Learning in Practice for Scientists, or CLIPS. CLIPS provides a multi-point mentoring model that has allowed us to successfully integrate the teaching and learning of a complex set of tacitly-understood skills across multiple scientific disciplines. It also provides a flexible way for industry experts, academics, and students to learn from one another's experiences of, and expertise in, science communication. CLIPS leverages the student focus on assessment; students access CLIPS for pragmatic, detailed, and consistent advice when undertaking assessment tasks. In creating CLIPS, our philosophy was that communication is the core business of any scientific practice, not an add-on after the event. Extensive, repeated use of CLIPS by both students and academics indicates that the resource and its delivery model are considered useful, respected, and impactful for, and by, the intended audiences. We have provided CLIPS to the science education community through www.clips.edu.au.}, } @article {pmid29904534, year = {2018}, author = {Richter, K and Thomas, N}, title = {Science in the Eye of the Beer-Holder-How To Put On an Effective Pint of Science: The Adelaide Experience.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904534}, issn = {1935-7877}, abstract = {"Pint of Science" is an outreach activity bringing the latest scientific discoveries to the community in the relaxed atmosphere of a pub. Founded in the United Kingdom in 2012, this three-night festival in May is now held annually in cities around the world. Today, Pint of Science contributes to science education and engages peers and the public alike, demystifying science at a pub near you. This article gives advice about how to organize a Pint of Science festival, as exemplified by the Adelaide/South Australia chapter's 2017 experience.}, } @article {pmid29904533, year = {2018}, author = {Killikelly, A}, title = {Using the Tools of Informal Science Education to Connect Science and the Public.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904533}, issn = {1935-7877}, abstract = {Traditional modes of communication within the scientific community, including presentation of data at conferences and in peer-reviewed publications, use technical jargon that limits public engagement. While altering word choice is an important method for increasing public engagement, the data itself may not be enough. For example, communicating the lack of evidence that vaccines cause autism did not convince many reluctant parents to vaccinate their kids (Nyhan, Reifler, Richey, Freed, Pediatrics 133:e835-e842, 2014). To address this gap between the scientific community and the public, many journals are adopting open-access policies and publishing lay-abstracts. Meanwhile, "meet a scientist" programs are creating opportunities for scientists to engage with the public in person. However, these programs may not be as effective as they could be. Many scientists still subscribe to an information-deficit model in which "the data speaks for itself." Alternative tools that go beyond the data are needed. Here, I present three tools to create connections between the public and science: 3-D objects, games, and storytelling. These multidimensional and multisensory methods do more than promote understanding of scientific data; they may also be used to convey science as a verb and as an essential viewpoint in the human struggle for understanding.}, } @article {pmid29904532, year = {2018}, author = {Orr, D and Baram-Tsabari, A}, title = {Science and Politics in the Polio Vaccination Debate on Facebook: A Mixed-Methods Approach to Public Engagement in a Science-Based Dialogue.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904532}, issn = {1935-7877}, abstract = {This study examines the ways in which the public discusses and debates the scientific issue of vaccinations in the online social media environment of Facebook. We apply a mixed-methods approach, where a qualitative analysis is combined with a quantitative analysis of the characteristics of the debate on polio vaccinations in a Facebook group dedicated to parental and professional dialogue. The qualitative analysis suggested that dialogue became more political than scientific overall, yet the quantitative analysis showed that the discussants did not abandon the scientific nature of the issue at hand.}, } @article {pmid29904531, year = {2018}, author = {Todd, K and Haupt, G and Kollmann, EK and Pfeifle, S}, title = {Fostering Conversation about Synthetic Biology Between Publics and Scientists: A Comparison of Approaches and Outcomes.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904531}, issn = {1935-7877}, abstract = {Public engagement with science (PES) is an emerging outreach method that builds trust between scientists and public audiences by encouraging two-way conversations and mutual learning about science content and societal values. Building with Biology, a PES initiative focused on synthetic biology, distributed 182 kits with two types of products to informal science education institutions across the United States: 1) hands-on activities for public events, and 2) materials to run public dialogue programs, called forums. This article compares the interest levels, perceived value, and learning of public participants at these events and forums. Forum participants reported slightly higher levels of increased interest in future activities related to PES and synthetic biology; valued aspects of interpersonal interactions central to dialogue-based programming; and described learning about societal decision-making around synthetic biology. Event participants valued enjoyment and access to content and reported slightly larger learning gains. The current study may help program coordinators and educators thoughtfully select a PES product type that promotes outcomes aligned with their goals: events featuring hands-on activities may support greater understanding of scientific relevance, and forum programs might encourage learning and behavior that leads to deliberative processes.}, } @article {pmid29904530, year = {2018}, author = {Breitbart, M and Malki, K and Sawaya, NA and Bonnain, C and Martin, MO}, title = {Elementary Student Outreach Activity Demonstrating the Use of Phage Therapy Heroes to Combat Bacterial Infections.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904530}, issn = {1935-7877}, } @article {pmid29904529, year = {2018}, author = {O'Keeffe, K and Bain, R}, title = {ComSciCon-Triangle: Regional Science Communication Training for Graduate Students.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904529}, issn = {1935-7877}, abstract = {The ability of scientists to effectively communicate their research, and scientific ideas in general, with a variety of audiences is critical in both academic and non-academic careers. There is currently a dearth of formal and informal science communication training opportunities for graduate students in science, technology, engineering, and mathematics (STEM) fields. This curriculum paper introduces ComSciCon-Triangle, a graduate student-organized science communication workshop for graduate students in STEM at research universities in the Raleigh-Durham, North Carolina, region. Started in 2015, this annual workshop aims to empower graduate students to be more engaged in communicating their research with the public as well as with fellow scientists. Each workshop consists of interactive panel discussions with invited science communicators (science writers, academics, filmmakers, etc.), informal networking opportunities with invited guests and other attendees, and hands-on sessions for improving oral and written communication skills. Analyzing pre- and post-survey data from all ComSciCon-Triangle attendees from 2015 to 2017, we find that workshop attendees feel significantly more confident in their ability to communicate scientific ideas with both the general public and with other scientists, and more confident submitting a written piece to a popular science publication or journal. We discuss how ComSciCon-Triangle serves as a model for local science communication workshops "for graduate students, organized by graduate students."}, } @article {pmid29904528, year = {2018}, author = {Kimber, O and Cromley, JG and Molnar-Kimber, KL}, title = {Let Your Ideas Flow: Using Flowcharts to Convey Methods and Implications of the Results in Laboratory Exercises, Articles, Posters, and Slide Presentations.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904528}, issn = {1935-7877}, } @article {pmid29904526, year = {2018}, author = {Clement, WL and Elliott, KT and Cordova-Hoyos, O and Distefano, I and Kearns, K and Kumar, R and Leto, A and Tumaliuan, J and Franchetti, L and Kulesza, E and Tineo, N and Mendes, P and Roth, K and Osborn, JM}, title = {Tasting the Tree of Life: Development of a Collaborative, Cross-Campus, Science Outreach Meal Event.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904526}, issn = {1935-7877}, abstract = {Communicating about science with the public can present a number of challenges, from participation to engagement to impact. In an effort to broadly communicate messages regarding biodiversity, evolution, and tree-thinking with the campus community at The College of New Jersey (TCNJ), a public, primarily undergraduate institution, we created a campus-wide, science-themed meal, "Tasting the Tree of Life: Exploring Biodiversity through Cuisine." We created nine meals that incorporated 149 species/ingredients across the Tree of Life. Each meal illustrated a scientific message communicated through interactions with undergraduate biology students, informational signs, and an interactive website. To promote tree-thinking, we reconstructed a phylogeny of all 149 ingredients. In total, 3,262 people attended the meal, and evaluations indicated that participants left with greater appreciation for the biodiversity and evolutionary relatedness of their food. A keynote lecture and a coordinated social media campaign enhanced the scientific messages, and media coverage extended the reach of this event. "Tasting the Tree of Life" highlights the potential of cuisine as a valuable science communication tool.}, } @article {pmid29904525, year = {2018}, author = {Garcia, JT}, title = {Communicating Discovery-Based Research Results to the News: A Real-World Lesson in Science Communication for Undergraduate Students.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904525}, issn = {1935-7877}, abstract = {Communicating science effectively to the general public is a necessary skill that takes practice. Generally, undergraduate science majors are taught to communicate to other scientists but are not given formal training on how to communicate with a nonscientist. An opportunity to appear on a news segment can be used as a real-world lesson on science communication for your students. This article will describe how to contact a producer to get your class on a news segment, ideas for types of research that may be of interest to the media, and how to practice communicating the results effectively.}, } @article {pmid29904524, year = {2018}, author = {Dudo, A and Besley, J and Kahlor, LA and Koh, H and Copple, J and Yuan, S}, title = {Microbiologists' Public Engagement Views and Behaviors.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904524}, issn = {1935-7877}, abstract = {In this study, we present results from an extensive survey of US-based microbiologists (adults) to explore these scientists' perceptions and behaviors related to communicating their research. Specifically, we explored the frequency with which microbiologists engage in public communication, how they evaluate their public communication experiences, and the factors associated with their willingness to engage in face-to-face and online public communication in the future. Data from a multi-wave online survey suggest that microbiologists (N = 903) are somewhat frequent communicators who derive great value from their outreach efforts. The results further suggest that social and psychological drivers of future intentions to engage with the public are consistent with the Theory of Planned Behavior (TPB). Specifically, microbiologists with more positive attitudes toward engagement were more willing to partake in direct and online communication activities. Similarly, microbiologists who believe they possess communication skills are more willing than their less efficacious colleagues to do either type of outreach. Our results also indicate that more-senior and more-active researchers are more willing to participate in direct and online engagement. Implications for communication training are discussed.}, } @article {pmid29904523, year = {2018}, author = {Mayfield, TJ and Olimpo, JT and Floyd, KW and Greenbaum, E}, title = {Collaborative Posters Develop Students' Ability to Communicate about Undervalued Scientific Resources to Nonscientists.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904523}, issn = {1935-7877}, support = {RL5 GM118969/GM/NIGMS NIH HHS/United States ; TL4 GM118971/GM/NIGMS NIH HHS/United States ; UL1 GM118970/GM/NIGMS NIH HHS/United States ; }, abstract = {Scientists are increasingly called upon to communicate with the public, yet most never receive formal training in this area. Public understanding is particularly critical to maintaining support for undervalued resources such as biological collections, research data repositories, and expensive equipment. We describe activities carried out in an inquiry-driven organismal biology laboratory course designed to engage a diverse student body using biological collections. The goals of this cooperative learning experience were to increase students' ability to locate and comprehend primary research articles, and to communicate the importance of an undervalued scientific resource to nonscientists. Our results indicate that collaboratively created, research-focused informational posters are an effective tool for achieving these goals and may be applied in other disciplines or classroom settings.}, } @article {pmid29904522, year = {2018}, author = {Greer, S and Alexander, H and Baldwin, TO and Freeze, HH and Thompson, M and Hunt, G and Snowflack, DR}, title = {The Art of Science Communication-A Novel Approach to Science Communication Training.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, doi = {10.1128/jmbe.v19i1.1547}, pmid = {29904522}, issn = {1935-7877}, abstract = {Effective communication is a requisite skill for scientists. However, formalized training in this area is often unavailable for members of the scientific community. As one approach to combat this problem, the American Society for Biochemistry and Molecular Biology (ASBMB) developed The Art of Science Communication, an eight-week-long online course that provides facilitated instruction on how to communicate science in an oral format. The course is offered three times a year, and as of December 2017, nearly 200 individuals from all career stages have taken part in it. The course completion rate is currently 60%, a rate three to five times as high as the average for similar Massive Open Online Courses (MOOCs). Participants have indicated that taking the course has improved their ability to communicate about their research, and that the skills and lessons learned have benefited them professionally. Moving forward, we are examining approaches that will help us improve the course and expand its reach throughout the scientific community. This article details the development of the course and examines the role and potential of such training within the larger scientific community.}, } @article {pmid29904521, year = {2018}, author = {Gruss, AB}, title = {Communicating Microbiology Concepts from Multiple Contexts through Poster Presentations.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904521}, issn = {1935-7877}, abstract = {Accredited environmental engineering degrees require graduates to be able to apply their scholarship to concepts of professional practice and design. This transferable skill of relating what you learn in one setting to another situation is vital for all professions, not just engineering. A course project involving designing and presenting a professional poster was implemented to enhance student mastery in Environmental Engineering Microbiology while also developing communication and transferable skills vital for all majors. Students were asked to read a contemporary non-fiction book relating to microbiology and expand upon the book's thesis by integrating course content, news articles, and peer-reviewed journal articles. They then were required to present this information in class using a professional poster. Students felt the project allowed them to synthesize and organize information, analyze ideas, and integrate ideas from various sources. These transferable skills are vital for students and professionals alike to be able to communicate advanced information and master a topic.}, } @article {pmid29904520, year = {2018}, author = {Wang, JTH and Power, CJ and Kahler, CM and Lyras, D and Young, PR and Iredell, J and Robins-Browne, R}, title = {Communication Ambassadors-an Australian Social Media Initiative to Develop Communication Skills in Early Career Scientists.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904520}, issn = {1935-7877}, abstract = {Science communication is a skill set to be developed through ongoing interactions with different stakeholders across a variety of platforms. Opportunities to engage the general public are typically reserved for senior scientists, but the use of social media in science communication allows all scientists to instantaneously disseminate their findings and interact with online users. The Communication Ambassador program is a social media initiative launched by the Australian Society for Microbiology to expand the online presence and science communication portfolios of early-career scientists. Through their participation in the program, a rotating roster of Australian microbiologists have broadened the online reach of the Society's social media channels as well as their own professional networks by attending and live-tweeting microbiology events throughout the year. We present the Communication Ambassador program as a case study of coordinated social media activity in science communication to the general public, and describe the potential for its applications in science education and training.}, } @article {pmid29904519, year = {2018}, author = {Popovich, J and Stephens, M and Celaya, H and Suwarno, S and Barclay, S and Yee, E and Dean, DA and Farris, M and Haydel, SE}, title = {Building and Breaking the Cell Wall in Four Acts: A Kinesthetic and Tactile Role-Playing Exercise for Teaching Beta-Lactam Antibiotic Mechanism of Action and Resistance.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904519}, issn = {1935-7877}, abstract = {"Building and breaking the cell wall" is designed to review the bacterial cell envelope, previously learned in lower-division biology classes, while introducing new topics such as antibiotics and bacterial antibiotic resistance mechanisms. We developed a kinesthetic and tactile modeling activity where students act as cellular components and construct the cell wall. In the first two acts, students model a portion of the gram-positive bacterial cell envelope and then demonstrate in detail how the peptidoglycan is formed. Act III involves student demonstration of the addition of β-lactam antibiotics to the environment and how they inhibit the formation of peptidoglycan, thereby preventing bacterial replication. Using Staphylococcus aureus as a model for gram-positive bacteria, students finish the activity (Act IV) by acting out how S. aureus often becomes resistant to β-lactam antibiotics. A high level of student engagement was observed, and the activity received positive feedback. In an assessment administered prior to and two months after the activity, significant improvements in scores were observed (p < 0.0001), demonstrating increased understanding and retention. This activity allows students to (i) visualize, role play, and kinesthetically "build" the cell envelope and form the peptidoglycan layer, (ii) understand the mechanism of action for β-lactam antibiotics, as well as how gene acquisition and protein changes result in resistance, and (iii) work cooperatively and actively to promote long-term retention of the subject material.}, } @article {pmid29904518, year = {2018}, author = {Rauschenbach, I and Keddis, R and Davis, D}, title = {Poster Development and Presentation to Improve Scientific Inquiry and Broaden Effective Scientific Communication Skills.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904518}, issn = {1935-7877}, abstract = {We have redesigned a tried-and-true laboratory exercise into an inquiry-based team activity exploring microbial growth control, and implemented this activity as the basis for preparing a scientific poster in a large, multi-section laboratory course. Spanning most of the semester, this project culminates in a poster presentation of data generated from a student-designed experiment. Students use and apply the scientific method and improve written and verbal communication skills. The guided inquiry format of this exercise provides the opportunity for student collaboration through cooperative learning. For each learning objective, a percentage score was tabulated (learning objective score = points awarded/total possible points). A score of 80% was our benchmark for achieving each objective. At least 76% of the student groups participating in this project over two semesters achieved each learning goal. Student perceptions of the project were evaluated using a survey. Nearly 90% of participating students felt they had learned a great deal in the areas of formulating a hypothesis, experimental design, and collecting and analyzing data; 72% of students felt this project had improved their scientific writing skills. In a separate survey, 84% of students who responded felt that peer review was valuable in improving their final poster submission. We designed this inquiry-based poster project to improve student scientific communication skills. This exercise is appropriate for any microbiology laboratory course whose learning outcomes include the development of scientific inquiry and literacy.}, } @article {pmid29904517, year = {2018}, author = {McCartney, M and Childers, C and Baiduc, RR and Barnicle, K}, title = {Annotated Primary Literature: A Professional Development Opportunity in Science Communication for Graduate Students and Postdocs.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904517}, issn = {1935-7877}, abstract = {Formal training in communicating science to a general audience is not traditionally included in graduate and postdoctoral-level training programs. However, the ability to effectively communicate science is increasingly recognized as a responsibility of professional scientists. We describe a science communication professional development opportunity in which scientists at the graduate-level and above annotate primary scientific literature, effectively translating complex research into an accessible educational tool for undergraduate students. We examined different types of annotator training, each with its own populations and evaluation methods, and surveyed participants about why they participated, the confidence they have in their self-reported science communication skills, and how they plan to leverage this experience to advance their science careers. Additionally, to confirm that annotators were successful in their goal of making the original research article easier to read, we performed a readability analysis on written annotations and compared that with the original text of the published paper. We found that both types of annotator training led to a gain in participants' self-reported confidence in their science communication skills. Also, the annotations were significantly more readable than the original paper, indicating that the training was effective. The results of this work highlight the potential of annotator training to serve as a value-added component of scientific training at and above the graduate level.}, } @article {pmid29904516, year = {2018}, author = {Schwingel, JM}, title = {Enhancing Scientific Communication Through an Undergraduate Biology and Journalism Partnership.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904516}, issn = {1935-7877}, abstract = {Scientific terminology presents an obstacle to effective communication with nonscientific audiences. To overcome this obstacle, biology majors in a general microbiology elective completed a project involving two different audiences: a scientific audience of their peers and a general, nonscientific audience. First, students presented an overview of a primary research paper and the significance of its findings to a general, nonscientific audience in an elevator-type talk. This was followed by a peer interview with a student in a journalism course, in which the biology students needed to comprehend the article to effectively communicate it to the journalism students, and the journalism students needed to ask questions about an unfamiliar, technical topic. Next, the biology students wrote a summary of their article for a scientific audience. Finally, the students presented a figure from the article to their peers in a scientific, Bio-Minute format. The biology-journalism partnership allowed biology students to develop their ability to communicate scientific information and journalism students their ability to ask appropriate questions and establish a base of knowledge from which to write.}, } @article {pmid29904515, year = {2018}, author = {Grzyb, K and Snyder, W and Field, KG}, title = {Learning to Write Like a Scientist: A Writing-Intensive Course for Microbiology/Health Science Students.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904515}, issn = {1935-7877}, abstract = {Learning the tools and conventions of expert communication in the sciences provides multiple benefits to bioscience students, yet often these skills are not formally taught. To address this need, we designed a writing-intensive microbiology course on emerging infectious diseases to provide upper-division students with science-specific writing skills along with disciplinary course content. The course followed the guidelines of our university's Writing Intensive Curriculum (WIC) program. Students wrote a press release, a case study, a controversy/position paper, and a grant prospectus, and revised drafts after feedback. To assess the course, in 2015 and 2016 we administered pre-post surveys and collected writing samples for analysis. Students reported on their experience, training, skills, and knowledge before taking the course. They then rated the extent to which the assignments, lectures, in-class activities, and writing activities contributed to their attainment of the learning outcomes of the course. Students entering the class were inexperienced in tools of science writing and the specific genres covered by the class. Their confidence levels rose in both skills and knowledge. Feedback from instructors was cited as most helpful in the majority of the areas where students reported the most gains. The survey provided evidence that discipline-specific knowledge had been acquired through writing activities. Teaching science writing by allowing the students to write "fiction" (e.g., a case report about a fictional patient) was effective in maintaining a high level of interest, both in learning the conventions of the genre and in seeking out detailed information about emerging infectious diseases. Both the course structure and the specific assignments would be useful at other institutions to teach science writing.}, } @article {pmid29904514, year = {2018}, author = {Ponzio, NM and Alder, J and Nucci, M and Dannenfelser, D and Hilton, H and Linardopoulos, N and Lutz, C}, title = {Learning Science Communication Skills Using Improvisation, Video Recordings, and Practice, Practice, Practice.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904514}, issn = {1935-7877}, abstract = {Doctoral students in science disciplines spend countless hours learning how to conduct cutting-edge research but very little time learning to communicate the nature and significance of their science to people outside their field. To narrow this disparity, we created an unusual course titled Communicating Science for doctoral science trainees at Rutgers University. Our goal was to help students develop an advanced ability to communicate their research clearly and accurately and to emphasize its value and significance to diverse audiences. Course design included classroom instruction supplemented with improvisation, video recordings, and ample opportunity for students to practice and receive immediate, constructive feedback in a supportive environment. A multidisciplinary faculty with expertise in science, education, communication, and theater arts taught this course. PhD students came from diverse scientific disciplines, ranging from biology and chemistry to civil engineering. Students also completed a capstone project in which they worked with a professional in the academic or private sector to explore a possible career aspiration. Assessment was in the form of feedback on students' oral and poster presentations, and written abstracts about their research. Student evaluations and comments about course format and content were mostly positive and also provided input for ways to improve the course. We discovered that the diversity of scientific backgrounds among our students enhanced their ability to learn how to communicate their science to others outside their disciplines. We are leveraging the success of our initial course offering to reach other student and faculty groups at Rutgers.}, } @article {pmid29904513, year = {2018}, author = {Dela Cruz, TEE and Aril-Dela Cruz, JV}, title = {Communicating Science through Editorial Cartoons in Microbiology Classrooms.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904513}, issn = {1935-7877}, abstract = {The use of graphical illustration in lecture presentations can make a seemingly boring lesson more attractive and enticing to students. Creating science-themed illustrations and science-based narratives can also lead to creative and critical thinking among students. We used writing editorials and creating editorial cartoons as a learning activity to promote critical thinking and creative skills that are essential in communicating scientific information. This activity can be used with a range of audiences, at various educational levels and in basic to advanced courses.}, } @article {pmid29904512, year = {2018}, author = {Mehltretter Drury, SA and Bost, AG and Wysocki, LM and Ingram, AL}, title = {Encouraging Science Communication through Deliberative Pedagogy: A Study of a Gene Editing Deliberation in a Nonmajors Biology Course.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904512}, issn = {1935-7877}, abstract = {Deliberative pedagogy encourages productive science communication and learning through engagement and discussion of socio-scientific issues (SSI). This article examines a two-day deliberation module on gene editing that took place in an introductory nonmajors biology course, furthering research on integrating deliberative discussion into the biology classroom. The results demonstrate the benefits of a single, episodic deliberation in the classroom, which can positively encourage active discussion and critical awareness of connections between biology and real-world issues, thus contributing to the development of scientific citizenship. Additionally, the findings show that gene editing is an apt SSI topic for the deliberative process because it encourages productive communication practices of scientific citizenship, including discussion, perspective taking, questioning, and consideration of different types of evidence when coming to a decision.}, } @article {pmid29904511, year = {2018}, author = {Johnson, EA and Fankhauser, SC}, title = {Engaging in the Publication Process Improves Perceptions of Scientific Communication, Critique, and Career Skills Among Graduate Students.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904511}, issn = {1935-7877}, abstract = {Reading and critiquing primary scientific literature is an important skill for graduate students, as reviewing literature is critical to advancing science. Prior research indicates that graduate students lack understanding of effective communication as well as basic experimental design, but also that graduate students are capable of growth in their experimental design abilities when given proper opportunities. The Journal of Emerging Investigators (JEI) provides graduate students with the opportunity to review and edit original research papers submitted by middle and high school student-authors. The purpose of this project was to determine whether participation in the primary literature process through JEI effectively aids in developing graduate students' perceived abilities in the domains of communication, scientific critique, and career preparation. A 12-question survey was distributed using SurveyMonkey to 215 JEI reviewers and editors. Editors, whose role involves the synthesis of feedback from multiple reviewers and interaction with papers in their earliest stages, perceived that they benefited more than did reviewers in every domain assessed by the survey. Perceived impact on critiquing skills was only rated more highly by reviewers than by editors once the graduate students in question had reviewed 10 or more papers. The results of this research suggest that graduate students should participate early and often in the reading and reviewing of primary literature; furthermore, the study of flawed science writing can help to improve experimental design, critique, and science communication skills.}, } @article {pmid29904509, year = {2018}, author = {Pruneski, JA}, title = {Introducing Students to the Challenges of Communicating Science by Using a Tool That Employs Only the 1,000 Most Commonly Used Words.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904509}, issn = {1935-7877}, abstract = {Overcoming the complex and technical language used in science is a major barrier to scientists being able to communicate their work with the general public. This can lead to misunderstanding and mistrust of science, with many negative consequences. Scientists are increasingly seeking to improve their ability to communicate their work effectively with a variety of audiences. As such, students should recognize the challenges and importance of communicating science with nonscientists. This short classroom activity takes advantage of a free, web-based tool, called Simple Writer (https://xkcd.com/simplewriter/), which facilitates the writing and revising of text using only the 1,000 most commonly used words in English. Students are asked to write a paragraph in response to a prompt and use the Simple Writer tool to convert it into a form using only the 1,000 most commonly used words, while still maintaining the same message. By experiencing the difficulty of converting a relatively simple paragraph to meet to this criteria, students gain an appreciation for the challenge of removing jargon from scientific and other technical writing. Beyond the initial activity, the Simple Writer platform can be used in various other ways to engage students in learning science and developing essential writing skills.}, } @article {pmid29904508, year = {2018}, author = {Adler, JJ}, title = {Students "Tackle" Quantitative Literacy in their Science Communication with Real-World Football Activity.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904508}, issn = {1935-7877}, abstract = {Undergraduate introductory biology students struggle when communicating quantitative data. This activity provides students with a real-world research experience to improve their quantitative literacy in science communication. Students were provided with a national sports media report that described a professional football athlete requiring 9,000 calories daily. Students were then asked to determine whether, based on their own research and calculations, the reporter had correctly calculated the total calories coming from the reported foods. Students discovered that their different sources of caloric information provided very different (albeit accurate) calculated totals, ranging from 6,000 to 11,000 calories. Importantly, the students generated professional letters outlining their calculated differences and sent them to the sports reporter. The professional letters to the reporter were assessed via rubric for accuracy of calculations, appropriate research evidence, professionalism, and readability for a nonexpert. A majority of the students provided accurate calculations; however, students scored lower on their professional writing skills, ability to cite appropriate research evidence, and readability for a nonexpert. Additionally, summative quantitative problems were individually completed and assessed, and activity cohorts achieved significantly higher on these problems compared with the non-activity cohort. Finally, surveyed students indicated that the activity helped prepare them for quantitative problems on the summative exam and helped them identify major course learning objectives. In conclusion, given an authentic research activity, students can take ownership of their learning and practice their communication to the general public about quantitative scientific information.}, } @article {pmid29904507, year = {2018}, author = {Henriques, AC and De Marco, P}, title = {Simple Protocol for Molecular Fingerprinting of Human Oral Microbiota Samples in Lab Classes.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904507}, issn = {1935-7877}, abstract = {DNA fingerprinting is a major tool in identifying individuals and in evidence matching. However, this technique can be difficult to reproduce in practical classes. Here, we report on distinct PCR profiles obtained when amplifying saliva DNA of a score of distinct individuals with Random Amplified Polymorphic DNA (RAPD)-PCR primer BOXA1R. The RAPD-PCR method is simple and efficient for discrimination between bacterial strains and is used in this instance to obtain personalized fingerprints of each individual's oral microbiota. We present real results with undergraduate students confirming that this procedure is easily feasible in practical classes. Based on the results presented, we suggest a laboratory activity for undergraduate Molecular Biology or Microbiology students.}, } @article {pmid29904103, year = {2018}, author = {Perry, CT and Alvarez-Filip, L and Graham, NAJ and Mumby, PJ and Wilson, SK and Kench, PS and Manzello, DP and Morgan, KM and Slangen, ABA and Thomson, DP and Januchowski-Hartley, F and Smithers, SG and Steneck, RS and Carlton, R and Edinger, EN and Enochs, IC and Estrada-Saldívar, N and Haywood, MDE and Kolodziej, G and Murphy, GN and Pérez-Cervantes, E and Suchley, A and Valentino, L and Boenish, R and Wilson, M and Macdonald, C}, title = {Loss of coral reef growth capacity to track future increases in sea level.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {396-400}, doi = {10.1038/s41586-018-0194-z}, pmid = {29904103}, issn = {1476-4687}, mesh = {Animals ; Anthozoa/*growth & development/metabolism ; Atlantic Ocean ; Carbonates/metabolism ; Climate Change/*statistics & numerical data ; *Coral Reefs ; Indian Ocean ; Models, Theoretical ; Oceans and Seas ; Seawater/*analysis ; }, abstract = {Sea-level rise (SLR) is predicted to elevate water depths above coral reefs and to increase coastal wave exposure as ecological degradation limits vertical reef growth, but projections lack data on interactions between local rates of reef growth and sea level rise. Here we calculate the vertical growth potential of more than 200 tropical western Atlantic and Indian Ocean reefs, and compare these against recent and projected rates of SLR under different Representative Concentration Pathway (RCP) scenarios. Although many reefs retain accretion rates close to recent SLR trends, few will have the capacity to track SLR projections under RCP4.5 scenarios without sustained ecological recovery, and under RCP8.5 scenarios most reefs are predicted to experience mean water depth increases of more than 0.5 m by 2100. Coral cover strongly predicts reef capacity to track SLR, but threshold cover levels that will be necessary to prevent submergence are well above those observed on most reefs. Urgent action is thus needed to mitigate climate, sea-level and future ecological changes in order to limit the magnitude of future reef submergence.}, } @article {pmid29904083, year = {2018}, author = {Du Toit, A}, title = {Four is a crowd.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0044-x}, pmid = {29904083}, issn = {1740-1534}, } @article {pmid29904082, year = {2018}, author = {Martens, EC and Neumann, M and Desai, MS}, title = {Interactions of commensal and pathogenic microorganisms with the intestinal mucosal barrier.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0036-x}, pmid = {29904082}, issn = {1740-1534}, abstract = {The intestinal mucosal barrier is composed of epithelial cells that are protected by an overlying host-secreted mucous layer and functions as the first line of defence against pathogenic and non-pathogenic microorganisms. Some microorganisms have evolved strategies to either survive in the mucosal barrier or circumvent it to establish infection. In this Review, we discuss the current state of knowledge of the complex interactions of commensal microorganisms with the intestinal mucosal barrier, and we discuss strategies used by pathogenic microorganisms to establish infection by either exploiting different epithelial cell lineages or disrupting the mucous layer, as well as the role of defects in mucus production in chronic disease.}, } @article {pmid29904081, year = {2018}, author = {Du Toit, A}, title = {Breaking barriers.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0043-y}, pmid = {29904081}, issn = {1740-1534}, } @article {pmid29904080, year = {2018}, author = {Du Toit, A}, title = {ppGpp triggers the switch.}, journal = {Nature reviews. Microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1038/s41579-018-0042-z}, pmid = {29904080}, issn = {1740-1534}, } @article {pmid29903976, year = {2018}, author = {Goyette, SR}, title = {Hitting the wall.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1262}, doi = {10.1126/science.360.6394.1262}, pmid = {29903976}, issn = {1095-9203}, } @article {pmid29903975, year = {2018}, author = {Ota, S and Horisaki, R and Kawamura, Y and Ugawa, M and Sato, I and Hashimoto, K and Kamesawa, R and Setoyama, K and Yamaguchi, S and Fujiu, K and Waki, K and Noji, H}, title = {Ghost cytometry.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1246-1251}, doi = {10.1126/science.aan0096}, pmid = {29903975}, issn = {1095-9203}, mesh = {Cell Separation/*methods ; Cells/classification/*cytology ; Flow Cytometry/*methods ; Humans ; Image Cytometry/*methods ; MCF-7 Cells ; Machine Learning ; Single-Cell Analysis/*methods ; }, abstract = {Ghost imaging is a technique used to produce an object's image without using a spatially resolving detector. Here we develop a technique we term "ghost cytometry," an image-free ultrafast fluorescence "imaging" cytometry based on a single-pixel detector. Spatial information obtained from the motion of cells relative to a static randomly patterned optical structure is compressively converted into signals that arrive sequentially at a single-pixel detector. Combinatorial use of the temporal waveform with the intensity distribution of the random pattern allows us to computationally reconstruct cell morphology. More importantly, we show that applying machine-learning methods directly on the compressed waveforms without image reconstruction enables efficient image-free morphology-based cytometry. Despite a compact and inexpensive instrumentation, image-free ghost cytometry achieves accurate and high-throughput cell classification and selective sorting on the basis of cell morphology without a specific biomarker, both of which have been challenging to accomplish using conventional flow cytometers.}, } @article {pmid29903974, year = {2018}, author = {Khalaf, O and Resch, S and Dixsaut, L and Gorden, V and Glauser, L and Gräff, J}, title = {Reactivation of recall-induced neurons contributes to remote fear memory attenuation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1239-1242}, doi = {10.1126/science.aas9875}, pmid = {29903974}, issn = {1095-9203}, mesh = {Animals ; CA3 Region, Hippocampal/physiology ; Dentate Gyrus/cytology/*physiology ; Fear/*physiology ; Memory, Long-Term/*physiology ; Mental Recall/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Neurons/*physiology ; Proto-Oncogene Proteins c-fos/genetics ; }, abstract = {Whether fear attenuation is mediated by inhibition of the original memory trace of fear with a new memory trace of safety or by updating of the original fear trace toward safety has been a long-standing question in neuroscience and psychology alike. In particular, which of the two scenarios underlies the attenuation of remote (month-old) fear memories is completely unknown, despite the impetus to better understand this process against the backdrop of enduring traumata. We found-chemogenetically and in an engram-specific manner-that effective remote fear attenuation is accompanied by the reactivation of memory recall-induced neurons in the dentate gyrus and that the continued activity of these neurons is critical for fear reduction. This suggests that the original memory trace of fear actively contributes to remote fear attenuation.}, } @article {pmid29903973, year = {2018}, author = {Gaynor, KM and Hojnowski, CE and Carter, NH and Brashares, JS}, title = {The influence of human disturbance on wildlife nocturnality.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1232-1235}, doi = {10.1126/science.aar7121}, pmid = {29903973}, issn = {1095-9203}, mesh = {Animals ; Animals, Wild/*physiology ; Behavior, Animal/*physiology ; *Circadian Rhythm ; *Human Activities ; Humans ; Mammals/*physiology ; }, abstract = {Rapid expansion of human activity has driven well-documented shifts in the spatial distribution of wildlife, but the cumulative effect of human disturbance on the temporal dynamics of animals has not been quantified. We examined anthropogenic effects on mammal diel activity patterns, conducting a meta-analysis of 76 studies of 62 species from six continents. Our global study revealed a strong effect of humans on daily patterns of wildlife activity. Animals increased their nocturnality by an average factor of 1.36 in response to human disturbance. This finding was consistent across continents, habitats, taxa, and human activities. As the global human footprint expands, temporal avoidance of humans may facilitate human-wildlife coexistence. However, such responses can result in marked shifts away from natural patterns of activity, with consequences for fitness, population persistence, community interactions, and evolution.}, } @article {pmid29903972, year = {2018}, author = {Abdou, K and Shehata, M and Choko, K and Nishizono, H and Matsuo, M and Muramatsu, SI and Inokuchi, K}, title = {Synapse-specific representation of the identity of overlapping memory engrams.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1227-1231}, doi = {10.1126/science.aat3810}, pmid = {29903972}, issn = {1095-9203}, mesh = {Amnesia, Retrograde/physiopathology/psychology ; Amygdala/physiology ; Animals ; Auditory Perception ; Basolateral Nuclear Complex/physiology ; Conditioning, Classical ; Fear/psychology ; Long-Term Potentiation/*physiology ; Male ; Memory/*physiology ; Mental Recall/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Optogenetics ; Synapses/*physiology ; }, abstract = {Memories are integrated into interconnected networks; nevertheless, each memory has its own identity. How the brain defines specific memory identity out of intermingled memories stored in a shared cell ensemble has remained elusive. We found that after complete retrograde amnesia of auditory fear conditioning in mice, optogenetic stimulation of the auditory inputs to the lateral amygdala failed to induce memory recall, implying that the memory engram no longer existed in that circuit. Complete amnesia of a given fear memory did not affect another linked fear memory encoded in the shared ensemble. Optogenetic potentiation or depotentiation of the plasticity at synapses specific to one memory affected the recall of only that memory. Thus, the sharing of engram cells underlies the linkage between memories, whereas synapse-specific plasticity guarantees the identity and storage of individual memories.}, } @article {pmid29903971, year = {2018}, author = {Nürnberg, DJ and Morton, J and Santabarbara, S and Telfer, A and Joliot, P and Antonaru, LA and Ruban, AV and Cardona, T and Krausz, E and Boussac, A and Fantuzzi, A and Rutherford, AW}, title = {Photochemistry beyond the red limit in chlorophyll f-containing photosystems.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1210-1213}, doi = {10.1126/science.aar8313}, pmid = {29903971}, issn = {1095-9203}, mesh = {Chlorophyll/*analogs & derivatives/chemistry/radiation effects ; Chlorophyll A ; Cyanobacteria/growth & development/metabolism/*radiation effects ; Light ; Photosynthesis/*radiation effects ; Photosystem I Protein Complex/chemistry/*radiation effects ; Photosystem II Protein Complex/chemistry/*radiation effects ; }, abstract = {Photosystems I and II convert solar energy into the chemical energy that powers life. Chlorophyll a photochemistry, using red light (680 to 700 nm), is near universal and is considered to define the energy "red limit" of oxygenic photosynthesis. We present biophysical studies on the photosystems from a cyanobacterium grown in far-red light (750 nm). The few long-wavelength chlorophylls present are well resolved from each other and from the majority pigment, chlorophyll a. Charge separation in photosystem I and II uses chlorophyll f at 745 nm and chlorophyll f (or d) at 727 nm, respectively. Each photosystem has a few even longer-wavelength chlorophylls f that collect light and pass excitation energy uphill to the photochemically active pigments. These photosystems function beyond the red limit using far-red pigments in only a few key positions.}, } @article {pmid29903970, year = {2018}, author = {Eslami, SMA and Jimenez Rezende, D and Besse, F and Viola, F and Morcos, AS and Garnelo, M and Ruderman, A and Rusu, AA and Danihelka, I and Gregor, K and Reichert, DP and Buesing, L and Weber, T and Vinyals, O and Rosenbaum, D and Rabinowitz, N and King, H and Hillier, C and Botvinick, M and Wierstra, D and Kavukcuoglu, K and Hassabis, D}, title = {Neural scene representation and rendering.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1204-1210}, doi = {10.1126/science.aar6170}, pmid = {29903970}, issn = {1095-9203}, mesh = {*Machine Learning ; *Neural Networks (Computer) ; *Vision, Ocular ; }, abstract = {Scene representation-the process of converting visual sensory data into concise descriptions-is a requirement for intelligent behavior. Recent work has shown that neural networks excel at this task when provided with large, labeled datasets. However, removing the reliance on human labeling remains an important open problem. To this end, we introduce the Generative Query Network (GQN), a framework within which machines learn to represent scenes using only their own sensors. The GQN takes as input images of a scene taken from different viewpoints, constructs an internal representation, and uses this representation to predict the appearance of that scene from previously unobserved viewpoints. The GQN demonstrates representation learning without human labels or domain knowledge, paving the way toward machines that autonomously learn to understand the world around them.}, } @article {pmid29903969, year = {2018}, author = {Barbier, EB and Burgess, JC and Dean, TJ}, title = {Response-Conservation accord.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1196-1197}, doi = {10.1126/science.aau1746}, pmid = {29903969}, issn = {1095-9203}, mesh = {*Conservation of Natural Resources ; }, } @article {pmid29903968, year = {2018}, author = {Addison, PFE and Bull, JW}, title = {Conservation accord: Corporate incentives.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1195-1196}, doi = {10.1126/science.aau0788}, pmid = {29903968}, issn = {1095-9203}, mesh = {Conservation of Natural Resources ; *Motivation ; *Organizations ; }, } @article {pmid29903967, year = {2018}, author = {Ghazoul, J}, title = {Conservation accord: Cash is not enough.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1195}, doi = {10.1126/science.aau0798}, pmid = {29903967}, issn = {1095-9203}, mesh = {*Conservation of Natural Resources ; }, } @article {pmid29903966, year = {2018}, author = {Chen, M and Sun, Y and Yang, C and Zeng, G and Li, Z and Zhu, Y and Zhang, J}, title = {Conservation accord: Let countries govern.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1195}, doi = {10.1126/science.aat7724}, pmid = {29903966}, issn = {1095-9203}, mesh = {*Conservation of Natural Resources ; *Environment ; }, } @article {pmid29903965, year = {2018}, author = {Pinsky, ML and Reygondeau, G and Caddell, R and Palacios-Abrantes, J and Spijkers, J and Cheung, WWL}, title = {Preparing ocean governance for species on the move.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1189-1191}, doi = {10.1126/science.aat2360}, pmid = {29903965}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; Atmosphere ; Fisheries/*trends ; *Fishes ; Oceans and Seas ; Policy ; Temperature ; }, } @article {pmid29903964, year = {2018}, author = {Zwicker, M}, title = {Understanding spatial environments from images.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1188}, doi = {10.1126/science.aat9641}, pmid = {29903964}, issn = {1095-9203}, } @article {pmid29903963, year = {2018}, author = {Frankland, PW and Josselyn, SA}, title = {Facing your fears.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1186-1187}, doi = {10.1126/science.aau0035}, pmid = {29903963}, issn = {1095-9203}, mesh = {Animals ; *Behavior, Animal ; *Fear ; Mice ; }, } @article {pmid29903962, year = {2018}, author = {Benítez-López, A}, title = {Animals feel safer from humans in the dark.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1185-1186}, doi = {10.1126/science.aau1311}, pmid = {29903962}, issn = {1095-9203}, mesh = {Animals ; *Behavior, Animal ; Humans ; }, } @article {pmid29903961, year = {2018}, author = {Van Essen, DC}, title = {Scaling of human brain size.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1184-1185}, doi = {10.1126/science.aat8948}, pmid = {29903961}, issn = {1095-9203}, mesh = {*Brain ; Humans ; *Neurons ; Organ Size ; }, } @article {pmid29903960, year = {2018}, author = {Ramirez, S}, title = {Crystallizing a memory.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1182-1183}, doi = {10.1126/science.aau0043}, pmid = {29903960}, issn = {1095-9203}, mesh = {Brain/*physiology ; Humans ; Memory/*physiology ; Synapses/*physiology ; }, } @article {pmid29903959, year = {2018}, author = {Pikitch, EK}, title = {A tool for finding rare marine species.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1180-1182}, doi = {10.1126/science.aao3787}, pmid = {29903959}, issn = {1095-9203}, mesh = {Animals ; Aquatic Organisms/*classification/genetics ; DNA/*analysis/genetics ; *Endangered Species ; Environmental Monitoring/*methods ; Phylogeny ; Population ; Sequence Analysis, DNA/*methods ; Sharks/classification/genetics ; }, } @article {pmid29903958, year = {2018}, author = {Cohen, J}, title = {The Sunshine State's dark cloud.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1176-1179}, doi = {10.1126/science.360.6394.1176}, pmid = {29903958}, issn = {1095-9203}, mesh = {Epidemics/*prevention & control ; Florida/epidemiology ; HIV Infections/*epidemiology/*prevention & control/psychology ; Humans ; Incidence ; Needle-Exchange Programs ; Social Stigma ; }, } @article {pmid29903957, year = {2018}, author = {Cohen, J}, title = {The loyal opposition.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1175}, doi = {10.1126/science.360.6394.1175}, pmid = {29903957}, issn = {1095-9203}, mesh = {*Acquired Immunodeficiency Syndrome/drug therapy/economics/epidemiology/prevention & control ; Child ; Female ; Humans ; Moscow ; }, } @article {pmid29903956, year = {2018}, author = {Cohen, J}, title = {The pill exchange.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1174}, doi = {10.1126/science.360.6394.1174}, pmid = {29903956}, issn = {1095-9203}, mesh = {Acquired Immunodeficiency Syndrome/*drug therapy ; *Anti-Retroviral Agents ; Drug Storage ; Health Services Accessibility ; Humans ; Pharmacy ; Russia ; *Social Networking ; }, } @article {pmid29903955, year = {2018}, author = {Cohen, J}, title = {Poster couple.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1172}, doi = {10.1126/science.360.6394.1172}, pmid = {29903955}, issn = {1095-9203}, mesh = {Acquired Immunodeficiency Syndrome/*epidemiology/*psychology ; Family Characteristics ; Fear ; Female ; Humans ; Male ; Russia/epidemiology ; *Social Stigma ; }, } @article {pmid29903954, year = {2018}, author = {Cohen, J}, title = {Status symbol.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1171}, doi = {10.1126/science.360.6394.1171}, pmid = {29903954}, issn = {1095-9203}, mesh = {HIV Infections/*psychology ; Humans ; *Prejudice ; Russia ; *Social Stigma ; }, } @article {pmid29903953, year = {2018}, author = {Cohen, J}, title = {Dark nights, bright stars.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1170-1175}, doi = {10.1126/science.360.6394.1170}, pmid = {29903953}, issn = {1095-9203}, mesh = {*Epidemics ; Female ; HIV Infections/drug therapy/*epidemiology/prevention & control ; Humans ; *Malpractice ; Needle-Exchange Programs/methods ; Neglected Diseases/drug therapy/*epidemiology/prevention & control ; Pregnant Women ; Russia/epidemiology ; *Social Stigma ; }, } @article {pmid29903952, year = {2018}, author = {Cohen, J}, title = {Babies who dodge HIV may not be unscathed.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1168}, doi = {10.1126/science.360.6394.1168}, pmid = {29903952}, issn = {1095-9203}, mesh = {Anti-Retroviral Agents/adverse effects/therapeutic use ; Feces/microbiology ; *Gastrointestinal Microbiome ; HIV Infections/*epidemiology/*immunology ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*prevention & control ; *Maternal Health ; }, } @article {pmid29903951, year = {2018}, author = {Cohen, J}, title = {Building TRUST in an LGBTQ-hostile country.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1167}, doi = {10.1126/science.360.6394.1167}, pmid = {29903951}, issn = {1095-9203}, mesh = {Community Health Centers/*organization & administration ; Female ; HIV Infections/*epidemiology/*prevention & control/transmission ; Homosexuality, Male ; *Hostility ; Humans ; Male ; Nigeria/epidemiology ; *Sexual and Gender Minorities ; Transgender Persons ; }, } @article {pmid29903950, year = {2018}, author = {Cohen, J}, title = {The mother of all challenges.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1164-1169}, doi = {10.1126/science.360.6394.1164}, pmid = {29903950}, issn = {1095-9203}, mesh = {Epidemics/*prevention & control ; Female ; HIV/isolation & purification ; HIV Infections/blood/*prevention & control/*transmission ; *Hospitals, Maternity ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*prevention & control ; Poverty ; Pregnancy ; *Pregnant Women ; }, } @article {pmid29903949, year = {2018}, author = {Cohen, J}, title = {Far from over.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1162-1163}, doi = {10.1126/science.360.6394.1162}, pmid = {29903949}, issn = {1095-9203}, mesh = {Child ; Epidemics/*prevention & control ; Florida/epidemiology ; HIV Infections/*epidemiology/*prevention & control/transmission ; Humans ; Nigeria/epidemiology ; Population Density ; Risk ; Russia/epidemiology ; }, } @article {pmid29903948, year = {2018}, author = {Mervis, J}, title = {Stricter Chinese student visas raise alarm.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1161}, doi = {10.1126/science.360.6394.1161}, pmid = {29903948}, issn = {1095-9203}, mesh = {Asian Continental Ancestry Group ; China ; Education, Graduate/*legislation & jurisprudence ; Emigrants and Immigrants/*legislation & jurisprudence ; Humans ; Policy ; Students/*legislation & jurisprudence ; United States ; United States Government Agencies/*legislation & jurisprudence ; }, } @article {pmid29903947, year = {2018}, author = {Hand, E}, title = {Seafloor fiber optic cables can listen for earthquakes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1160}, doi = {10.1126/science.360.6394.1160}, pmid = {29903947}, issn = {1095-9203}, } @article {pmid29903946, year = {2018}, author = {Wadman, M}, title = {Report details persistent hostility to women in science.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1159}, doi = {10.1126/science.360.6394.1159}, pmid = {29903946}, issn = {1095-9203}, mesh = {Civil Rights/legislation & jurisprudence ; Fear ; Female ; *Hostility ; Humans ; Science ; Sexism/legislation & jurisprudence/*prevention & control ; Sexual Harassment/legislation & jurisprudence/*prevention & control ; *Women ; }, } @article {pmid29903945, year = {2018}, author = {Popkin, G}, title = {Quantum physics could get big boost from U.S. Congress.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1158-1159}, doi = {10.1126/science.360.6394.1158}, pmid = {29903945}, issn = {1095-9203}, } @article {pmid29903944, year = {2018}, author = {Langin, K}, title = {Seaweed masses assault Caribbean islands.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1157-1158}, doi = {10.1126/science.360.6394.1157}, pmid = {29903944}, issn = {1095-9203}, mesh = {Animals ; Fisheries ; Fishes ; *Harmful Algal Bloom ; *Introduced Species ; *Sargassum ; Satellite Imagery ; *Seaweed ; Turtles ; West Indies ; }, } @article {pmid29903943, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1154-1156}, doi = {10.1126/science.360.6394.1154}, pmid = {29903943}, issn = {1095-9203}, } @article {pmid29903942, year = {2018}, author = {Abdool Karim, Q and Abdool Karim, SS}, title = {HIV-No time for complacency.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1153}, doi = {10.1126/science.aau2663}, pmid = {29903942}, issn = {1095-9203}, mesh = {AIDS Vaccines ; Acquired Immunodeficiency Syndrome/drug therapy/*epidemiology/*prevention & control ; Anti-Retroviral Agents/administration & dosage/adverse effects/therapeutic use ; Epidemics/*prevention & control ; Global Health ; HIV/isolation & purification ; Humans ; Incidence ; Pre-Exposure Prophylaxis ; Safe Sex ; United Nations ; }, } @article {pmid29903941, year = {2018}, author = {Forzieri, G and Alkama, R and Miralles, DG and Cescatti, A}, title = {Response to Comment on "Satellites reveal contrasting responses of regional climate to the widespread greening of Earth".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {}, doi = {10.1126/science.aap9664}, pmid = {29903941}, issn = {1095-9203}, mesh = {*Climate ; Climate Change ; *Earth (Planet) ; Ecosystem ; Plant Leaves ; Temperature ; }, abstract = {Li et al contest the idea that vegetation greening has contributed to boreal warming and argue that the sensitivity of temperature to leaf area index (LAI) is instead likely driven by the climate impact on vegetation. We provide additional evidence that the LAI-climate interplay is indeed largely driven by the vegetation impact on temperature and not vice versa, thus corroborating our original conclusions.}, } @article {pmid29903940, year = {2018}, author = {Li, Y and Zeng, Z and Huang, L and Lian, X and Piao, S}, title = {Comment on "Satellites reveal contrasting responses of regional climate to the widespread greening of Earth".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {}, doi = {10.1126/science.aap7950}, pmid = {29903940}, issn = {1095-9203}, mesh = {*Climate ; *Climate Change ; Earth (Planet) ; Ecosystem ; Temperature ; }, abstract = {Forzieri et al (Reports, 16 June 2017, p. 1180) used satellite data to show that boreal greening caused regional warming. We show that this positive sensitivity of temperature to the greening can be derived from the positive response of vegetation to boreal warming, which indicates that results from a statistical regression with satellite data should be carefully interpreted.}, } @article {pmid29903939, year = {2018}, author = {Roy, SK and Sauer, VTK and Westwood-Bachman, JN and Venkatasubramanian, A and Hiebert, WK}, title = {Improving mechanical sensor performance through larger damping.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {}, doi = {10.1126/science.aar5220}, pmid = {29903939}, issn = {1095-9203}, abstract = {Mechanical resonances are used in a wide variety of devices, from smartphone accelerometers to computer clocks and from wireless filters to atomic force microscopes. Frequency stability, a critical performance metric, is generally assumed to be tantamount to resonance quality factor (the inverse of the linewidth and of the damping). We show that the frequency stability of resonant nanomechanical sensors can be improved by lowering the quality factor. At high bandwidths, quality-factor reduction is completely mitigated by increases in signal-to-noise ratio. At low bandwidths, notably, increased damping leads to better stability and sensor resolution, with improvement proportional to damping. We confirm the findings by demonstrating temperature resolution of 60 microkelvin at 300-hertz bandwidth. These results open the door to high-performance ultrasensitive resonators in gaseous or liquid environments, single-cell nanocalorimetry, nanoscale gas chromatography, atmospheric-pressure nanoscale mass spectrometry, and new approaches in crystal oscillator stability.}, } @article {pmid29903938, year = {2018}, author = {Polonsky, M and Rimer, J and Kern-Perets, A and Zaretsky, I and Miller, S and Bornstein, C and David, E and Kopelman, NM and Stelzer, G and Porat, Z and Chain, B and Friedman, N}, title = {Induction of CD4 T cell memory by local cellular collectivity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {}, doi = {10.1126/science.aaj1853}, pmid = {29903938}, issn = {1095-9203}, mesh = {Animals ; CD4 Lymphocyte Count ; CD4-Positive T-Lymphocytes/*cytology/*immunology ; Cell Differentiation/genetics/*immunology ; Computer Simulation ; Gene Expression ; *Immunologic Memory ; Interleukin-2/genetics/immunology ; Interleukin-6/genetics/immunology ; L-Selectin/genetics/immunology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Models, Immunological ; Quorum Sensing/*immunology ; Sequence Analysis, RNA ; Signaling Lymphocytic Activation Molecule Family/immunology ; }, abstract = {Cell differentiation is directed by signals driving progenitors into specialized cell types. This process can involve collective decision-making, when differentiating cells determine their lineage choice by interacting with each other. We used live-cell imaging in microwell arrays to study collective processes affecting differentiation of naïve CD4+ T cells into memory precursors. We found that differentiation of precursor memory T cells sharply increases above a threshold number of locally interacting cells. These homotypic interactions involve the cytokines interleukin-2 (IL-2) and IL-6, which affect memory differentiation orthogonal to their effect on proliferation and survival. Mathematical modeling suggests that the differentiation rate is continuously modulated by the instantaneous number of locally interacting cells. This cellular collectivity can prioritize allocation of immune memory to stronger responses.}, } @article {pmid29903904, year = {2018}, author = {Tosh, N and Ferguson, J and Seoighe, C}, title = {History by the numbers?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5840}, pmid = {29903904}, issn = {1091-6490}, } @article {pmid29903903, year = {2018}, author = {Currie, TE and Turchin, P and Whitehouse, H and François, P and Feeney, K and Mullins, D and Hoyer, D and Collins, C and Grohmann, S and Savage, P and Mendel-Gleason, G and Turner, E and Dupeyron, A and Cioni, E and Reddish, J and Levine, J and Jordan, G and Brandl, E and Williams, A and Cesaretti, R and Krueger, M and Ceccarelli, A and Figliulo-Rosswurm, J and Tuan, PJ and Peregrine, P and Marciniak, A and Preiser-Kapeller, J and Kradin, N and Korotayev, A and Palmisano, A and Baker, D and Bidmead, J and Bol, P and Christian, D and Cook, C and Covey, A and Feinman, G and Júlíusson, ÁD and Kristinsson, A and Miksic, J and Mostern, R and Petrie, C and Rudiak-Gould, P and Ter Haar, B and Wallace, V and Mair, V and Xie, L and Baines, J and Bridges, E and Manning, J and Lockhart, B and Bogaard, A and Spencer, C}, title = {Reply to Tosh et al.: Quantitative analyses of cultural evolution require engagement with historical and archaeological research.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5841-E5842}, pmid = {29903903}, issn = {1091-6490}, mesh = {*Archaeology ; *Cultural Evolution ; Research ; }, } @article {pmid29903902, year = {2018}, author = {Alix-Garcia, JM and Sims, KRE and Orozco-Olvera, VH and Costica, LE and Fernández Medina, JD and Romo Monroy, S}, title = {Payments for environmental services supported social capital while increasing land management.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7016-7021}, pmid = {29903902}, issn = {1091-6490}, mesh = {Conservation of Natural Resources/*economics ; Humans ; Mexico ; *Models, Economic ; *Social Capital ; }, abstract = {Payments for environmental services (PES) programs incentivize landowners to protect or improve natural resources. Many conservationists fear that introducing compensation for actions previously offered voluntarily will reduce social capital (the institutions, relationships, attitudes, and values that govern human interactions), yet little rigorous research has investigated this concern. We examined the land cover management and communal social capital impacts of Mexico's federal conservation payments program, which is a key example for other countries committed to reducing deforestation, protecting watersheds, and conserving biodiversity. We used a regression discontinuity (RD) methodology to identify causal program effects, comparing outcomes for PES participants and similar rejected applicants close to scoring cutoffs. We found that payments increased land cover management activities, such as patrolling for illegal activity, building fire breaks, controlling pests, or promoting soil conservation, by ∼50%. Importantly, increases in paid activities as a result of PES did not crowd out unpaid contributions to land management or other prosocial work. Community social capital increased by ∼8-9%, and household-level measures of trust were not affected by the program. These findings demonstrate that major environmental conditional cash transfer programs can support both land management and the attitudes and institutions underpinning prosocial behavior. Rigorous empirical research on this question can proceed only country by country because of methodological limitations, but will be an important line of inquiry as PES continues to expand worldwide.}, } @article {pmid29903901, year = {2018}, author = {Kim, JH and Komatsu, M and Shin-Ya, K and Omura, S and Ikeda, H}, title = {Distribution and functional analysis of the phosphopantetheinyl transferase superfamily in Actinomycetales microorganisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6828-6833}, pmid = {29903901}, issn = {1091-6490}, mesh = {Actinomycetales/enzymology/*genetics ; Amino Acid Motifs ; Bacterial Proteins/*genetics ; *Databases, Protein ; *Multigene Family ; Transferases (Other Substituted Phosphate Groups)/*genetics ; }, abstract = {Phosphopantetheinyl transferases (PPTases) are a superfamily of essential enzymes required for the synthetic processes of many compounds including fatty acid, polyketide, and nonribosomal peptide metabolites. These enzymes activate carrier proteins in specific biosynthetic pathways via the transfer of a phosphopantetheinyl moiety to a serine residue in the conserved motif of carrier proteins. Since many Actinomycetales microorganisms produce a number of polyketide and nonribosomal peptide metabolites, the distribution of PPTase genes was investigated in these microorganisms. PPTases were found in bacterial protein databases using a hidden Markov model search with the PF01648 (4'-phosphopantetheinyl transferase superfamily) model. Actinomycetales microorganisms harbor several genes encoding AcpS-type and Sfp-type PPTases in individual genomes, many of which were associated with the biosynthetic gene cluster for polyketide or nonribosomal peptide metabolites. The properties of these PPTases were evaluated in the heterologous expression system using the biosynthetic gene clusters and genes encoding PPTases found in the present study. Sfp-type PPTases were classified into two subgroups, and although the substrate specificities of the enzymes in one subgroup were wide, the catalytic activities of enzymes in the other subgroup were low. SAV_1784 of Streptomyces avermitilis possessed the most characteristic broad-range activity against several type I polyketide synthases and nonribosomal peptide synthetases.}, } @article {pmid29903886, year = {2018}, author = {Mattila, S and Pérez-Torres, M and Efstathiou, A and Mimica, P and Fraser, M and Kankare, E and Alberdi, A and Aloy, MÁ and Heikkilä, T and Jonker, PG and Lundqvist, P and Martí-Vidal, I and Meikle, WPS and Romero-Cañizales, C and Smartt, SJ and Tsygankov, S and Varenius, E and Alonso-Herrero, A and Bondi, M and Fransson, C and Herrero-Illana, R and Kangas, T and Kotak, R and Ramírez-Olivencia, N and Väisänen, P and Beswick, RJ and Clements, DL and Greimel, R and Harmanen, J and Kotilainen, J and Nandra, K and Reynolds, T and Ryder, S and Walton, NA and Wiik, K and Östlin, G}, title = {A dust-enshrouded tidal disruption event with a resolved radio jet in a galaxy merger.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {482-485}, doi = {10.1126/science.aao4669}, pmid = {29903886}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Tidal disruption events (TDEs) are transient flares produced when a star is ripped apart by the gravitational field of a supermassive black hole (SMBH). We have observed a transient source in the western nucleus of the merging galaxy pair Arp 299 that radiated >1.5 × 1052 erg at infrared and radio wavelengths but was not luminous at optical or x-ray wavelengths. We interpret this as a TDE with much of its emission reradiated at infrared wavelengths by dust. Efficient reprocessing by dense gas and dust may explain the difference between theoretical predictions and observed luminosities of TDEs. The radio observations resolve an expanding and decelerating jet, probing the jet formation and evolution around a SMBH.}, } @article {pmid29903885, year = {2018}, author = {Qiu, C and Liu, F and Xu, L and Deng, B and Xiao, M and Si, J and Lin, L and Zhang, Z and Wang, J and Guo, H and Peng, H and Peng, LM}, title = {Dirac-source field-effect transistors as energy-efficient, high-performance electronic switches.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6400}, pages = {387-392}, doi = {10.1126/science.aap9195}, pmid = {29903885}, issn = {1095-9203}, abstract = {An efficient way to reduce the power consumption of electronic devices is to lower the supply voltage, but this voltage is restricted by the thermionic limit of subthreshold swing (SS), 60 millivolts per decade, in field-effect transistors (FETs). We show that a graphene Dirac source (DS) with a much narrower electron density distribution around the Fermi level than that of conventional FETs can lower SS. A DS-FET with a carbon nanotube channel provided an average SS of 40 millivolts per decade over four decades of current at room temperature and high device current I60 of up to 40 microamperes per micrometer at 60 millivolts per decade. When compared with state-of-the-art silicon 14-nanometer node FETs, a similar on-state current Ion is realized but at a much lower supply voltage of 0.5 volts (versus 0.7 volts for silicon) and a much steeper SS below 35 millivolts per decade in the off-state.}, } @article {pmid29903884, year = {2018}, author = {Gonen, N and Futtner, CR and Wood, S and Garcia-Moreno, SA and Salamone, IM and Samson, SC and Sekido, R and Poulat, F and Maatouk, DM and Lovell-Badge, R}, title = {Sex reversal following deletion of a single distal enhancer of Sox9.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1469-1473}, pmid = {29903884}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; T32 GM008061/GM/NIGMS NIH HHS/United States ; //Cancer Research UK/United Kingdom ; //Medical Research Council/United Kingdom ; }, mesh = {Animals ; Conserved Sequence ; Enhancer Elements, Genetic/*genetics ; Female ; Gonadal Dysgenesis, 46,XY/*genetics ; Humans ; Male ; Mice ; SOX9 Transcription Factor/*genetics ; Sequence Deletion ; Sex Determination Processes/*genetics ; Sex-Determining Region Y Protein/genetics/*metabolism ; Testis/*embryology ; Transcription Initiation Site ; }, abstract = {Cell fate decisions require appropriate regulation of key genes. Sox9, a direct target of SRY, is pivotal in mammalian sex determination. In vivo high-throughput chromatin accessibility techniques, transgenic assays, and genome editing revealed several novel gonadal regulatory elements in the 2-megabase gene desert upstream of Sox9 Although others are redundant, enhancer 13 (Enh13), a 557-base pair element located 565 kilobases 5' from the transcriptional start site, is essential to initiate mouse testis development; its deletion results in XY females with Sox9 transcript levels equivalent to those in XX gonads. Our data are consistent with the time-sensitive activity of SRY and indicate a strict order of enhancer usage. Enh13 is conserved and embedded within a 32.5-kilobase region whose deletion in humans is associated with XY sex reversal, suggesting that it is also critical in humans.}, } @article {pmid29903883, year = {2018}, author = {Nogly, P and Weinert, T and James, D and Carbajo, S and Ozerov, D and Furrer, A and Gashi, D and Borin, V and Skopintsev, P and Jaeger, K and Nass, K and Båth, P and Bosman, R and Koglin, J and Seaberg, M and Lane, T and Kekilli, D and Brünle, S and Tanaka, T and Wu, W and Milne, C and White, T and Barty, A and Weierstall, U and Panneels, V and Nango, E and Iwata, S and Hunter, M and Schapiro, I and Schertler, G and Neutze, R and Standfuss, J}, title = {Retinal isomerization in bacteriorhodopsin captured by a femtosecond x-ray laser.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {}, doi = {10.1126/science.aat0094}, pmid = {29903883}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Aspartic Acid/chemistry ; Bacteriorhodopsins/*chemistry/*radiation effects ; Ion Transport ; Isomerism ; Protein Conformation ; Retinaldehyde/*chemistry/*radiation effects ; Schiff Bases/chemistry ; Time Factors ; Water/chemistry ; X-Rays ; }, abstract = {Ultrafast isomerization of retinal is the primary step in photoresponsive biological functions including vision in humans and ion transport across bacterial membranes. We used an x-ray laser to study the subpicosecond structural dynamics of retinal isomerization in the light-driven proton pump bacteriorhodopsin. A series of structural snapshots with near-atomic spatial resolution and temporal resolution in the femtosecond regime show how the excited all-trans retinal samples conformational states within the protein binding pocket before passing through a twisted geometry and emerging in the 13-cis conformation. Our findings suggest ultrafast collective motions of aspartic acid residues and functional water molecules in the proximity of the retinal Schiff base as a key facet of this stereoselective and efficient photochemical reaction.}, } @article {pmid29903882, year = {2018}, author = {Lelieveld, J and Bourtsoukidis, E and Brühl, C and Fischer, H and Fuchs, H and Harder, H and Hofzumahaus, A and Holland, F and Marno, D and Neumaier, M and Pozzer, A and Schlager, H and Williams, J and Zahn, A and Ziereis, H}, title = {The South Asian monsoon-pollution pump and purifier.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {270-273}, doi = {10.1126/science.aar2501}, pmid = {29903882}, issn = {1095-9203}, mesh = {Air Pollutants/*chemistry ; *Air Pollution ; Asia ; Models, Theoretical ; Seasons ; *Wind ; }, abstract = {Air pollution is growing fastest in monsoon-affected South Asia. During the dry winter monsoon, the fumes disperse toward the Indian Ocean, creating a vast pollution haze, but their fate during the wet summer monsoon has been unclear. We performed atmospheric chemistry measurements by aircraft in the Oxidation Mechanism Observations campaign, sampling the summer monsoon outflow in the upper troposphere between the Mediterranean and the Indian Ocean. The measurements, supported by model calculations, show that the monsoon sustains a remarkably efficient cleansing mechanism by which contaminants are rapidly oxidized and deposited to Earth's surface. However, some pollutants are lofted above the monsoon clouds and chemically processed in a reactive reservoir before being redistributed globally, including to the stratosphere.}, } @article {pmid29903881, year = {2018}, author = {Marra, G and Clivati, C and Luckett, R and Tampellini, A and Kronjäger, J and Wright, L and Mura, A and Levi, F and Robinson, S and Xuereb, A and Baptie, B and Calonico, D}, title = {Ultrastable laser interferometry for earthquake detection with terrestrial and submarine cables.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6401}, pages = {486-490}, doi = {10.1126/science.aat4458}, pmid = {29903881}, issn = {1095-9203}, abstract = {Detecting ocean-floor seismic activity is crucial for our understanding of the interior structure and dynamic behavior of Earth. However, 70% of the planet's surface is covered by water, and seismometer coverage is limited to a handful of permanent ocean bottom stations. We show that existing telecommunication optical fiber cables can detect seismic events when combined with state-of-the-art frequency metrology techniques by using the fiber itself as the sensing element. We detected earthquakes over terrestrial and submarine links with lengths ranging from 75 to 535 kilometers and a geographical distance from the earthquake's epicenter ranging from 25 to 18,500 kilometers. Implementing a global seismic network for real-time detection of underwater earthquakes requires applying the proposed technique to the existing extensive submarine optical fiber network.}, } @article {pmid29903612, year = {2018}, author = {Bentlage, B and Osborn, KJ and Lindsay, DJ and Hopcroft, RR and Raskoff, KA and Collins, AG}, title = {Corrigendum to Loss of metagenesis and evolution of a parasitic life style in a group of open-ocean jellyfish Molecular Phylogenetics and Evolution 124 (2018) 50-59.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {390-391}, doi = {10.1016/j.ympev.2018.06.017}, pmid = {29903612}, issn = {1095-9513}, } @article {pmid29903534, year = {2018}, author = {Pogrebniak, KL and Curtis, C}, title = {Harnessing Tumor Evolution to Circumvent Resistance.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {639-651}, doi = {10.1016/j.tig.2018.05.007}, pmid = {29903534}, issn = {0168-9525}, support = {R01 CA182514/CA/NCI NIH HHS/United States ; }, abstract = {High-throughput sequencing can be used to measure changes in tumor composition across space and time. Specifically, comparisons of pre- and post-treatment samples can reveal the underlying clonal dynamics and resistance mechanisms. Here, we discuss evidence for distinct modes of tumor evolution and their implications for therapeutic strategies. In addition, we consider the utility of spatial tissue sampling schemes, single-cell analysis, and circulating tumor DNA to track tumor evolution and the emergence of resistance, as well as approaches that seek to forestall resistance by targeting tumor evolution. Ultimately, characterization of the (epi)genomic, transcriptomic, and phenotypic changes that occur during tumor progression coupled with computational and mathematical modeling of tumor evolutionary dynamics may inform personalized treatment strategies.}, } @article {pmid29903533, year = {2018}, author = {Hou, J and van Leeuwen, J and Andrews, BJ and Boone, C}, title = {Genetic Network Complexity Shapes Background-Dependent Phenotypic Expression.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {578-586}, pmid = {29903533}, issn = {0168-9525}, support = {R01 HG005853/HG/NHGRI NIH HHS/United States ; }, abstract = {The phenotypic consequences of a given mutation can vary across individuals. This so-called background effect is widely observed, from mutant fitness of loss-of-function variants in model organisms to variable disease penetrance and expressivity in humans; however, the underlying genetic basis often remains unclear. Taking insights gained from recent large-scale surveys of genetic interaction and suppression analyses in yeast, we propose that the genetic network context for a given mutation may shape its propensity of exhibiting background-dependent phenotypes. We argue that further efforts in systematically mapping the genetic interaction networks beyond yeast will provide not only key insights into the functional properties of genes, but also a better understanding of the background effects and the (un)predictability of traits in a broader context.}, } @article {pmid29903419, year = {2018}, author = {Norris, SJ}, title = {Catching up with Lyme Disease Antigenic Variation Computationally.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {644-645}, doi = {10.1016/j.tim.2018.05.017}, pmid = {29903419}, issn = {1878-4380}, abstract = {The spirochetes that cause Lyme disease have an elaborate antigenic variation system that produces millions of variants, thus evading the immune response. Verhey et al. have applied next-generation sequencing and computational analysis to gain new insights into how these bacteria keep 'one step ahead' of elimination by the host.}, } @article {pmid29903418, year = {2018}, author = {Szijártó, V and Nagy, E and Nagy, G}, title = {Directly Bactericidal Anti-Escherichia coli Antibody.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {642-644}, doi = {10.1016/j.tim.2018.05.016}, pmid = {29903418}, issn = {1878-4380}, abstract = {Monoclonal antibodies are considered promising therapeutic alternatives to fight antibiotic-resistant bacteria. Upon binding to their targets, they either act alone (e.g., by neutralizing bacterial toxins) or in concert with the host's immune system (with complement or phagocytes). Storek et al. have described a unique, directly bactericidal antibody against Escherichia coli.}, } @article {pmid29903417, year = {2018}, author = {Rossi, SL and Ebel, GD and Shan, C and Shi, PY and Vasilakis, N}, title = {Did Zika Virus Mutate to Cause Severe Outbreaks?.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {877-885}, pmid = {29903417}, issn = {1878-4380}, support = {R01 AI067380/AI/NIAID NIH HHS/United States ; R01 AI127744/AI/NIAID NIH HHS/United States ; R21 AI125996/AI/NIAID NIH HHS/United States ; U01 AI115577/AI/NIAID NIH HHS/United States ; UL1 TR001439/TR/NCATS NIH HHS/United States ; }, abstract = {Zika virus (ZIKV) has challenged the assumed knowledge regarding the pathobiology of flaviviruses. Despite causing sporadic and mild disease in the 50 years since its discovery, Zika virus has now caused multiple outbreaks in dozens of countries worldwide. Moreover, the disease severity in recent outbreaks, with neurological disease in adult and devastating congenital malformations in fetuses, was not previously seen. One hypothesis is that the virus has acquired mutations that have increased its virulence. Indeed, mutations in other arboviruses, such as West Nile virus (WNV), chikungunya virus (CHIKV), and Venezuelan equine encephalitis virus (VEEV), have enhanced outbreaks. This possibility, as well as alternative hypotheses, are explored here.}, } @article {pmid29903050, year = {2018}, author = {Madrazo, L and Lee, CB and McConnell, M and Khamisa, K}, title = {Self-assessment differences between genders in a low-stakes objective structured clinical examination (OSCE).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {393}, pmid = {29903050}, issn = {1756-0500}, support = {Education Grant//Ottawa Hospital Research Institute (CA)/ ; }, mesh = {Academic Performance/*psychology ; Adult ; *Clinical Competence ; Education, Medical, Undergraduate ; Female ; Humans ; Male ; Peer Group ; *Self-Assessment ; Sex Factors ; Students, Medical/*psychology ; Young Adult ; }, abstract = {OBJECTIVE: Physicians and medical students are generally poor-self assessors. Research suggests that this inaccuracy in self-assessment differs by gender among medical students whereby females underestimate their performance compared to their male counterparts. However, whether this gender difference in self-assessment is observable in low-stakes scenarios remains unclear. Our study's objective was to determine whether self-assessment differed between male and female medical students when compared to peer-assessment in a low-stakes objective structured clinical examination.

RESULTS: Thirty-three (15 males, 18 females) third-year students participated in a 5-station mock objective structured clinical examination. Trained fourth-year student examiners scored their performance on a 6-point Likert-type global rating scale. Examinees also scored themselves using the same scale. To examine gender differences in medical students' self-assessment abilities, mean self-assessment global rating scores were compared with peer-assessment global rating scores using an independent samples t test. Overall, female students' self-assessment scores were significantly lower compared to peer-assessment (p < 0.001), whereas no significant difference was found between self- and peer-assessment scores for male examinees (p = 0.228). This study provides further evidence that underestimation in self-assessment among females is observable even in a low-stakes formative objective structured clinical examination facilitated by fellow medical students.}, } @article {pmid29903043, year = {2018}, author = {Piangerelli, M and Rucco, M and Tesei, L and Merelli, E}, title = {Topolnogical classifier for detecting the emergence of epileptic seizures.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {392}, pmid = {29903043}, issn = {1756-0500}, support = {FP7-ICT-318121//FP7 Information and Communication Technologies/ ; }, mesh = {Algorithms ; Child ; Electroencephalography/classification/*methods ; Entropy ; Humans ; Seizures/classification/*diagnosis/physiopathology ; *Signal Processing, Computer-Assisted ; }, abstract = {OBJECTIVE: An innovative method based on topological data analysis is introduced for classifying EEG recordings of patients affected by epilepsy. We construct a topological space from a collection of EEGs signals using Persistent Homology; then, we analyse the space by Persistent entropy, a global topological feature, in order to classify healthy and epileptic signals.

RESULTS: The performance of the resulting one-feature-based linear topological classifier is tested by analysing the Physionet dataset. The quality of classification is evaluated in terms of the Area Under Curve (AUC) of the receiver operating characteristic curve. It is shown that the linear topological classifier has an AUC equal to [Formula: see text] while the performance of a classifier based on Sample Entropy has an AUC equal to 62.0%.}, } @article {pmid29903041, year = {2018}, author = {Zhao, L and Huang, Y and Lu, L and Yang, W and Huang, T and Lin, Z and Lin, C and Kwan, H and Wong, HLX and Chen, Y and Sun, S and Xie, X and Fang, X and Yang, H and Wang, J and Zhu, L and Bian, Z}, title = {Saturated long-chain fatty acid-producing bacteria contribute to enhanced colonic motility in rats.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {107}, pmid = {29903041}, issn = {2049-2618}, support = {FRG2/15-16/001, FRG2/16-17/003//Faculty Research Grant of Hong Kong Baptist University/International ; C2012-15G//The Research Grants Council of Hong Kong Collaborative Research Fund/International ; 2016A050503039//Guangdong-Hong Kong Technology Cooperation Funding Scheme/International ; }, mesh = {Animals ; Bacteroidetes/*metabolism ; Biodiversity ; Colon/microbiology/physiology ; Disease Models, Animal ; Dysbiosis/microbiology ; Fatty Acids/*analysis ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome ; Gastrointestinal Motility/*physiology ; Gastrointestinal Tract/microbiology ; Germ-Free Life ; Lactobacillus/*metabolism ; Maternal Deprivation ; Muscle Contraction/physiology ; Prevotella/*metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: The gut microbiota is closely associated with gastrointestinal (GI) motility disorder, but the mechanism(s) by which bacteria interact with and affect host GI motility remains unclear. In this study, through using metabolomic and metagenomic analyses, an animal model of neonatal maternal separation (NMS) characterized by accelerated colonic motility and gut dysbiosis was used to investigate the mechanism underlying microbiota-driven motility dysfunction.

RESULTS: An excess of intracolonic saturated long-chain fatty acids (SLCFAs) was associated with enhanced bowel motility in NMS rats. Heptadecanoic acid (C17:0) and stearic acid (C18:0), as the most abundant odd- and even-numbered carbon SLCFAs in the colon lumen, can promote rat colonic muscle contraction and increase stool frequency. Increase of SLCFAs was positively correlated with elevated abundances of Prevotella, Lactobacillus, and Alistipes. Functional annotation found that the level of bacterial LCFA biosynthesis was highly enriched in NMS group. Essential synthetic genes Fabs were largely identified from the genera Prevotella, Lactobacillus, and Alistipes. Pseudo germ-free (GF) rats receiving fecal microbiota from NMS donors exhibited increased defecation frequency and upregulated bacterial production of intracolonic SLCFAs. Modulation of gut dysbiosis by neomycin effectively attenuated GI motility and reduced bacterial SLCFA generation in the colon lumen of NMS rats.

CONCLUSIONS: These findings reveal a previously unknown relationship between gut bacteria, intracolonic SLCFAs, and host GI motility, suggesting the importance of SLCFA-producing bacteria in GI motility disorders. Further exploration of this relationship could lead to a precise medication targeting the gut microbiota for treating GI motility disorders.}, } @article {pmid29903040, year = {2018}, author = {Vona, B and Hofrichter, MAH and Schröder, J and Shehata-Dieler, W and Nanda, I and Haaf, T}, title = {Hereditary hearing loss SNP-microarray pilot study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {391}, pmid = {29903040}, issn = {1756-0500}, support = {HA 1374/7-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {DNA Copy Number Variations ; Datasets as Topic ; Genome-Wide Association Study/*methods ; Hearing Loss/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Microarray Analysis/*methods ; Pilot Projects ; Polymorphism, Single Nucleotide ; }, abstract = {OBJECTIVES: Despite recent advancements in diagnostic tools, the genomic landscape of hereditary hearing loss remains largely uncharacterized. One strategy to understand genome-wide aberrations includes the analysis of copy number variation that can be mapped using SNP-microarray technology. A growing collection of literature has begun to uncover the importance of copy number variation in hereditary hearing loss. This pilot study underpins a larger effort that involves the stage-wise analysis of hearing loss patients, many of whom have advanced to high-throughput sequencing analysis.

DATA DESCRIPTION: Our data originate from the Infinium HumanOmni1-Quad v1.0 SNP-microarrays (Illumina) that provide useful markers for genome-wide association studies and copy number variation analysis. This dataset comprises a cohort of 108 individuals (99 with hearing loss, 9 normal hearing family members) for the purpose of understanding the genetic contribution of copy number variations to hereditary hearing loss. These anonymized SNP-microarray data have been uploaded to the NCBI Gene Expression Omnibus and are intended to benefit other investigators interested in aggregating platform-matched array patient datasets or as part of a supporting reference tool for other laboratories to better understand recurring copy number variations in other genetic disorders.}, } @article {pmid29903004, year = {2018}, author = {Maynard, C and Cummins, I and Green, J and Weinkove, D}, title = {A bacterial route for folic acid supplementation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {67}, pmid = {29903004}, issn = {1741-7007}, support = {BB/J014516/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: To prevent folate deficiencies, many countries supplement various foodstuffs with folic acid. This compound is a synthetic oxidised folate that differs from naturally occurring reduced folates in its metabolism and uptake. Notably, safety reviews of folic acid supplementation have not considered interactions with gut bacteria. Here, we use the Caenorhabditis elegans - Escherichia coli animal- microbe model to examine a possible bacterial route for folic acid uptake. It has been assumed that supplements are taken up directly by the worm, especially because E. coli is unable to take up folates. However, E. coli, like many other bacteria, can transport the folate breakdown product, para-aminobenzoate-glutamate (PABA-glu), via AbgT and use it for bacterial folate synthesis. This pathway may impact host health because inhibition of bacterial folate synthesis increases C. elegans lifespan.

RESULTS: Folic acid supplementation was found to rescue a C. elegans developmental folate-deficient mutant; however, a much higher concentration was required compared to folinic acid, a reduced folate. Unlike folinic acid, the effectiveness of folic acid supplementation was dependent on the E. coli gene, abgT, suggesting a bacterial route with PABA-glu uptake by E. coli as a first step. Surprisingly, we found up to 4% PABA-glu in folic acid preparations, including in a commercial supplement. Via breakdown to PABA-glu, folic acid increases E. coli folate synthesis. This pathway restores folate synthesis in a bacterial mutant defective in PABA synthesis, reversing the ability of this mutant to increase C. elegans lifespan.

CONCLUSIONS: Folic acid supplementation in C. elegans occurs chiefly indirectly via bacterial uptake of breakdown products via E. coli AbgT, and can impact C. elegans development and longevity. Examining how folic acid supplementation affects bacterial folate synthesis in the human gut may help us to better understand the safety of folic acid supplementation.}, } @article {pmid29902991, year = {2018}, author = {Chen, L and Shi, S and Jiang, N and Khanzada, H and Wassan, GM and Zhu, C and Peng, X and Xu, J and Chen, Y and Yu, Q and He, X and Fu, J and Chen, X and Hu, L and Ouyang, L and Sun, X and He, H and Bian, J}, title = {Genome-wide analysis of long non-coding RNAs affecting roots development at an early stage in the rice response to cadmium stress.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {460}, pmid = {29902991}, issn = {1471-2164}, support = {2016YFD0101801//Ministry of Science and Technology of the People's Republic of China/ ; 31560386//National Natural Science Foundation of China/ ; GJJ170241//Science and Technology Research Project of Jiangxi/ ; }, mesh = {Cadmium/*toxicity ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Genome, Plant ; High-Throughput Nucleotide Sequencing ; Oryza/drug effects/*genetics/growth & development/metabolism ; Plant Roots/anatomy & histology/drug effects/growth & development/metabolism ; RNA, Long Noncoding/*metabolism ; Real-Time Polymerase Chain Reaction ; Stress, Physiological/genetics ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) have been found to play a vital role in several gene regulatory networks involved in the various biological processes in plants related to stress response. However, systematic analyses of lncRNAs expressed in rice Cadmium (Cd) stress are seldom studied. Thus, we presented the characterization and expression of lncRNAs in rice root development at an early stage in response to Cd stress.

RESULTS: The lncRNA deep sequencing revealed differentially expressed lncRNAs among Cd stress and normal condition. In the Cd stress group, 69 lncRNAs were up-regulated and 75 lncRNAs were down-regulated. Furthermore, 386 matched lncRNA-mRNA pairs were detected for 120 differentially expressed lncRNAs and 362 differentially expressed genes in cis, and target gene-related pathway analyses exhibited significant variations in cysteine and methionine metabolism pathway-related genes. For the genes in trans, overall, 28,276 interaction relationships for 144 lncRNAs and differentially expressed protein-coding genes were detected. The pathway analyses found that secondary metabolites, such as phenylpropanoids and phenylalanine, and photosynthesis pathway-related genes were significantly altered by Cd stress. All of these results indicate that lncRNAs may regulate genes of cysteine-rich peptide metabolism in cis, as well as secondary metabolites and photosynthesis in trans, to activate various physiological and biochemical reactions to respond to excessive Cd.

CONCLUSION: The present study could provide a valuable resource for lncRNA studies in response to Cd treatment in rice. It also expands our knowledge about lncRNA biological function and contributes to the annotation of the rice genome.}, } @article {pmid29902971, year = {2018}, author = {Zhang, Y and Wang, L and Gao, Y and Li, D and Yu, J and Zhou, R and Zhang, X}, title = {Genetic dissection and fine mapping of a novel dt gene associated with determinate growth habit in sesame.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {38}, pmid = {29902971}, issn = {1471-2156}, support = {2017NWB033//the Project of Crop Germplasm Resources Protection/ ; NICGR2017-014//the National Infrastructure for Crop Germplasm Resources/ ; 2013BAD01B03-08//the National Science-technology Support Plan Project/ ; CAAS-ASTIP-2013-OCRI//the Agricultural Science and Technology Innovation Project of Chinese Academy of Agricultural Sciences/ ; }, abstract = {BACKGROUND: As an important oil crop, growth habit of sesame (Sesamum indicum L.) is naturally indeterminate, which brings about asynchronous maturity of capsules and causes loss of yield.

RESULTS: The genetic basis of determinate growth habit in sesame was investigated by classical genetic analysis through multiple populations, results revealed that it was controlled by an unique recessive gene. The genotyping by sequencing (GBS) approach was employed for high-throughput SNP identification and genotyping in the F2 population, then a high density bin map was constructed, the map was 1086.403 cM in length, which consisted of 1184 bins (13,679 SNPs), with an average of 0.918 cM between adjacent bins. Based on bin mapping in conjunction with SSR markers analysis in targeted region, the novel sesame determinacy gene was mapped on LG09 in a genome region of 41 kb.

CONCLUSIONS: This study dissected genetic basis of determinate growth habit in sesame, constructed a new high-density bin map and mapped a novel determinacy gene. Results of this study demonstrate that we employed an optimized approach to get fine-accuracy, high-resolution and high-efficiency mapping result in sesame. The findings provided important foundation for sesame determinacy gene cloning and were expected to be applied in breeding for cultivars suited to mechanized production.}, } @article {pmid29902970, year = {2018}, author = {Yeom, SJ and Kim, M and Kim, SK and Lee, DH and Kwon, KK and Lee, H and Kim, H and Kim, DM and Lee, SG}, title = {Molecular and biochemical characterization of a novel isoprene synthase from Metrosideros polymorpha.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {118}, pmid = {29902970}, issn = {1471-2229}, support = {2015M3D3A1A01064875//the C1 Gas Refinery Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Science, ICT & Future Planning/ ; 2011-0031944//the Intelligent Synthetic Biology Center of the Global Frontier Project/ ; }, mesh = {Alkyl and Aryl Transferases/*genetics/isolation & purification/metabolism ; Butadienes/metabolism ; Cloning, Molecular ; Electrophoresis, Polyacrylamide Gel ; Escherichia coli ; Genes, Plant/genetics ; Hemiterpenes/metabolism ; Microorganisms, Genetically-Modified ; Myrtaceae/*enzymology/genetics ; Phylogeny ; Plant Proteins/*genetics/isolation & purification/metabolism ; Sequence Alignment ; }, abstract = {BACKGROUND: Isoprene is a five-carbon chemical that is an important starting material for the synthesis of rubber, elastomers, and medicines. Although many plants produce huge amounts of isoprene, it is very difficult to obtain isoprene directly from plants because of its high volatility and increasing environmental regulations. Over the last decade, microorganisms have emerged as a promising alternative host for efficient and sustainable bioisoprene production. Isoprene synthase (IspS) has received much attention for the conversion of isoprene from dimethylallyl diphosphate (DMAPP). Herein, we isolated a highly expressible novel IspS gene from Metrosideros polymorpha (MpIspS), which was cloned and expressed in Escherichia coli, using a plant cDNA library and characterized its molecular and biochemical properties.

RESULTS: The signal sequence deleted MpIspS was cloned and expressed in E. coli as a 65-kDa monomer. The maximal activity of the purified MpIspS was observed at pH 6.0 and 55 °C in the presence of 5 mM Mn2+. The Km, kcat, and kcat/Km for DMAPP as a substrate were 8.11 mM, 21 min- 1, and 2.59 mM- 1 min- 1, respectively. MpIspS was expressed along with the exogenous mevalonate pathway to produce isoprene in E. coli. The engineered cells produced isoprene concentrations of up to 23.3 mg/L using glycerol as the main carbon source.

CONCLUSION: MpIspS was expressed in large amounts in E. coli, which led to increased enzymatic activity and resulted in isoprene production in vivo. These results demonstrate a new IspS enzyme that is useful as a key biocatalyst for bioisoprene production in engineered microbes.}, } @article {pmid29902968, year = {2018}, author = {Gibrat, JF}, title = {A short note on dynamic programming in a band.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {226}, pmid = {29902968}, issn = {1471-2105}, abstract = {BACKGROUND: Third generation sequencing technologies generate long reads that exhibit high error rates, in particular for insertions and deletions which are usually the most difficult errors to cope with. The only exact algorithm capable of aligning sequences with insertions and deletions is a dynamic programming algorithm.

RESULTS: In this note, for the sake of efficiency, we consider dynamic programming in a band. We show how to choose the band width in function of the long reads' error rates, thus obtaining an [Formula: see text] algorithm in space and time. We also propose a procedure to decide whether this algorithm, when applied to semi-global alignments, provides the optimal score.

CONCLUSIONS: We suggest that dynamic programming in a band is well suited to the problem of aligning long reads between themselves and can be used as a core component of methods for obtaining a consensus sequence from the long reads alone. The function implementing the dynamic programming algorithm in a band is available, as a standalone program, at: https://forgemia.inra.fr/jean-francois.gibrat/BAND_DYN_PROG.git.}, } @article {pmid29902967, year = {2018}, author = {Qi, P and Gimode, D and Saha, D and Schröder, S and Chakraborty, D and Wang, X and Dida, MM and Malmberg, RL and Devos, KM}, title = {UGbS-Flex, a novel bioinformatics pipeline for imputation-free SNP discovery in polyploids without a reference genome: finger millet as a case study.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {117}, pmid = {29902967}, issn = {1471-2229}, support = {Award 1865/FN-SR/2013//Fulbright-Nehru Senior Research Fellowship/ ; DE-SC0010743//U.S. Department of Energy/ ; }, mesh = {Chromosome Mapping/methods ; Computational Biology/methods ; DNA, Plant/genetics ; Eleusine/*genetics ; Genetic Linkage ; Genome, Plant/genetics ; Genotyping Techniques/*methods ; Polymorphism, Single Nucleotide/*genetics ; *Polyploidy ; Sequence Analysis, DNA/methods ; Software ; }, abstract = {BACKGROUND: Research on orphan crops is often hindered by a lack of genomic resources. With the advent of affordable sequencing technologies, genotyping an entire genome or, for large-genome species, a representative fraction of the genome has become feasible for any crop. Nevertheless, most genotyping-by-sequencing (GBS) methods are geared towards obtaining large numbers of markers at low sequence depth, which excludes their application in heterozygous individuals. Furthermore, bioinformatics pipelines often lack the flexibility to deal with paired-end reads or to be applied in polyploid species.

RESULTS: UGbS-Flex combines publicly available software with in-house python and perl scripts to efficiently call SNPs from genotyping-by-sequencing reads irrespective of the species' ploidy level, breeding system and availability of a reference genome. Noteworthy features of the UGbS-Flex pipeline are an ability to use paired-end reads as input, an effective approach to cluster reads across samples with enhanced outputs, and maximization of SNP calling. We demonstrate use of the pipeline for the identification of several thousand high-confidence SNPs with high representation across samples in an F3-derived F2 population in the allotetraploid finger millet. Robust high-density genetic maps were constructed using the time-tested mapping program MAPMAKER which we upgraded to run efficiently and in a semi-automated manner in a Windows Command Prompt Environment. We exploited comparative GBS with one of the diploid ancestors of finger millet to assign linkage groups to subgenomes and demonstrate the presence of chromosomal rearrangements.

CONCLUSIONS: The paper combines GBS protocol modifications, a novel flexible GBS analysis pipeline, UGbS-Flex, recommendations to maximize SNP identification, updated genetic mapping software, and the first high-density maps of finger millet. The modules used in the UGbS-Flex pipeline and for genetic mapping were applied to finger millet, an allotetraploid selfing species without a reference genome, as a case study. The UGbS-Flex modules, which can be run independently, are easily transferable to species with other breeding systems or ploidy levels.}, } @article {pmid29902966, year = {2018}, author = {Wang, YX and Hu, Y and Zhu, YF and Baloch, AW and Jia, XM and Guo, AX}, title = {Transcriptional and physiological analyses of short-term Iron deficiency response in apple seedlings provide insight into the regulation involved in photosynthesis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {461}, pmid = {29902966}, issn = {1471-2164}, support = {2015-3-76//Lanzhou Science and Technology Bureau/ ; GSLT2016-1//Gansu Forestry Department/ ; 145RJZA167//Natural Science Foundation of Gansu Province/ ; }, mesh = {Carboxylic Ester Hydrolases/metabolism ; Chlorophyll ; Fluorescence ; Gene Expression Profiling ; Iron/chemistry/*physiology ; Malus/enzymology/*genetics/growth & development/metabolism ; Photosynthesis/*genetics ; Real-Time Polymerase Chain Reaction ; Seedlings/enzymology/genetics/metabolism ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: Iron (Fe) is an essential micronutrient for plants. Utilization of Fe deficiency-tolerant rootstock is an effective strategy to prevent Fe deficiency problems in fruit trees production. Malus halliana is an apple rootstock that is resistant to Fe deficiency; however, few molecular studies have been conducted on M. halliana.

RESULTS: To evaluate short-term molecular response of M. halliana leaves under Fe deficiency condition, RNA sequencing (RNA-Seq) analyses were conducted at 0 (T1), 0.5 (T2) and 3 d (T3) after Fe-deficiency stress, and the timepoints were determined with a preliminary physiological experiment. In all, 6907, 5328, and 3593 differentially expressed genes (DEGs) were identified in pairs of T2 vs. T1, T3 vs. T1, and T3 vs. T2. Several of the enriched DEGs were related to heme binding, Fe ion binding, thylakoid membranes, photosystem II, photosynthesis-antenna protein, porphyrin and chlorophyll metabolism and carotenoid biosynthesis under Fe deficiency, which suggests that Fe deficiency mainly affects the photosynthesis of M. halliana. Additionally, we found that Fe deficiency induced significant down-regulation in genes involved in photosynthesis at T2 when seedlings were treated with Fe-deficient solution for 0.5 d, indicating that there was a rapid response of M. halliana to Fe deficiency. A strong up-regulation of photosynthesis genes was detected at T3, which suggested that M. halliana was able to recover photosynthesis after prolonged Fe starvation. A similar expression pattern was found in pigment regulation, including genes for coding chlorophyllide a oxygenase (CAO), β-carotene hydroxylase (β-OHase), zeaxanthin epoxidase (ZEP) and 9-cis-epoxycarotenoid dioxygenase (NCED). Our results suggest that pigment regulation plays an important role in the Fe deficiency response. In addition, we verified sixteen genes related to photosynthesis-antenna protein, porphyrin and chlorophyll metabolism and carotenoid biosynthesis pathways using quantitative real-time PCR (qRT-PCR) to ensure the accuracy of transcriptome data. Photosynthetic parameters, Chl fluorescence parameters and the activity of Chlase were also determined.

CONCLUSIONS: This study broadly characterizes a molecular mechanism in which pigment and photosynthesis-related regulations play indispensable roles in the response of M. halliana to short-term Fe deficiency and provides a basis for future analyses of the key genes involved in the tolerance of Fe deficiency.}, } @article {pmid29902965, year = {2018}, author = {Abdulaal, WH}, title = {Purification and characterization of α-amylase from Trichoderma pseudokoningii.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {4}, pmid = {29902965}, issn = {1471-2091}, support = {438-130-696//the Deanship of Scientific Research (DSR) at King Abdulaziz University, Jeddah/International ; }, mesh = {Chromatography, Ion Exchange ; Citrus sinensis/microbiology ; Electrophoresis, Polyacrylamide Gel ; Enzyme Stability ; Fermentation ; Fungal Proteins/*isolation & purification/*metabolism ; Hot Temperature ; Hydrogen-Ion Concentration ; Isoenzymes/isolation & purification/metabolism ; Molecular Weight ; Substrate Specificity ; Trichoderma/*enzymology/growth & development ; alpha-Amylases/*isolation & purification/*metabolism ; }, abstract = {BACKGROUND: Previous studies have demonstrated that members of Trichoderma are able to generate appreciable amount of extracellular amylase and glucoamylase on soluble potato starch. In this study the α-amylase was purified and characterized from Trichoderma pseudokoningii grown on orange peel under solid state fermentation (SSF).

RESULTS: Five α-amylases A1-A5 from Trichodrma pseudokoningii were separated on DEAE-Sepharose column. The homogeneity of α-amylase A4 was detected after chromatography on Sephacryl S-200. α-Amylase A4 had molecular weight of 30 kDa by Sephacryl S-200 and SDS-PAGE. The enzyme had a broad pH optimum ranged from 4.5 to 8.5. The optimum temperature of A4 was 50 °C with high retention of its activity from 30 to 80 °C. The thermal stability of A4 was detected up to 50 °C and the enzyme was highly stable till 80 °C after 1 h incubation. All substrate analogues tested had amylase activity toward A4 ranged from 12 to 100% of its initial activity. The Km and Vmax values of A4 were 4 mg starch/ml and 0.74 μmol reducing sugar, respectively. The most of metals tested caused moderate inhibitory effect, except of Ca2+ and Mg2+ enhanced the activity. Hg2+ and Cd+ 2 strongly inhibited the activity of A4. EDTA as metal chelator caused strong inhibitory effect.

CONCLUSIONS: The properties of the purified α-amylase A4 from T. pseudokoningii meet the prerequisites needed for several applications.}, } @article {pmid29902797, year = {2018}, author = {Switonski, M and Dzimira, S and Aleksiewicz, R and Szczerbal, I and Nowacka-Woszuk, J and Krzeminska, P and Deska, T and Nizanski, W}, title = {Hypospadias Is Not Rare in Dogs: Five New Cases, a Retrospective Study, and a Review of the Literature.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {}, number = {}, pages = {}, doi = {10.1159/000490079}, pmid = {29902797}, issn = {1661-5433}, abstract = {Hypospadias, the abnormal position of the urethral orifice, is considered a rare congenital malformation of the reproductive organs in male dogs. We present 5 new cases of hypospadias - 2 of the penile type in German Shepherd Dogs and 3 perineal types in a Bavarian Mountain Hound, a French Bulldog, and an American Staffordshire Terrier. Other abnormalities (rudimentary or underdeveloped penis, incompletely formed preputial sheath, and bilateral cryptorchidism) were also observed. Molecular analysis of all cases revealed the presence of Y-linked genes (SRY and ZFY). Cytogenetic and histological analysis could be performed for only 2 cases: a normal male sex chromosome complement (78,XY) and spermatogenetically inactive testicles were observed. A retrospective search for hypospadias in 19,950 medical records of male dogs from a single veterinary clinic in Poland (2006-2017) was also performed. Altogether, 10 reports of penile hypospadias were found (0.05%). The majority of the reports concerned German Shepherd Dogs (8 cases among 1,511 male dogs of this breed), and thus, the estimated incidence of hypospadias in this breed was 0.5%. Moreover, we performed a review of 26 cases of canine hypospadias reported in the years 2004-2017. Our study and the review of the literature suggest that hypospadias is not rare in dogs and that some breeds (such as German Shepherd Dog and Boston Terrier) may be prone to this disorder.}, } @article {pmid29902792, year = {2018}, author = {De Lorenzi, L and Arrighi, S and Rossi, E and Grignani, P and Previderè, C and Bonacina, S and Cremonesi, F and Parma, P}, title = {XY (SRY-positive) Ovarian Disorder of Sex Development in Cattle.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {4}, pages = {196-203}, doi = {10.1159/000489869}, pmid = {29902792}, issn = {1661-5433}, mesh = {Alleles ; Animals ; Base Sequence ; Cattle ; Clitoris/pathology ; Cytogenetic Analysis ; Disorders of Sex Development/*genetics ; Female ; Genetic Markers ; Ovary/*pathology ; Sex-Determining Region Y Protein/*genetics ; Uterus/pathology ; }, abstract = {In mammals, the sex of the embryo depends on the SRY gene. In the presence of at least one intact and functional copy of this genetic factor (XY embryo) undifferentiated gonads will develop as testicles that subsequently determine the male phenotype. When this factor is not present, i.e., in subjects with 2 X chromosomes, an alternative pathway induces the development of ovaries, hence a female phenotype. In this case study, we describe a female cattle affected by a disorder of sex development (DSD). The subject, despite having a chromosomal XY constitution, did not develop testicles but ovaries, although they were underdeveloped. Moreover, genetic analysis highlighted the presence of the SRY gene with a normal coding region in both blood- and tissue-derived DNA. A chimeric condition was excluded in blood by sexing more than 350 cells and by allele profile investigation of 18 microsatellite markers. Array CGH analysis showed the presence of a not yet described 99-kb duplication (BTA18), but its relationship with the phenotype remains to be demonstrated. Gonadal histology demonstrated paired ovaries: the left one containing a large corpus luteum and the right one showing an underdeveloped aspect and very few early follicles. To our knowledge, we describe the first case of XY (SRY+) DSD in cattle with a normal SRY gene coding sequence.}, } @article {pmid29902574, year = {2018}, author = {Schield, DR and Adams, RH and Card, DC and Corbin, AB and Jezkova, T and Hales, NR and Meik, JM and Perry, BW and Spencer, CL and Smith, LL and García, GC and Bouzid, NM and Strickland, JL and Parkinson, CL and Borja, M and Castañeda-Gaytán, G and Bryson, RW and Flores-Villela, OA and Mackessy, SP and Castoe, TA}, title = {Cryptic genetic diversity, population structure, and gene flow in the Mojave rattlesnake (Crotalus scutulatus).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {669-681}, doi = {10.1016/j.ympev.2018.06.013}, pmid = {29902574}, issn = {1095-9513}, abstract = {The Mojave rattlesnake (Crotalus scutulatus) inhabits deserts and arid grasslands of the western United States and Mexico. Despite considerable interest in its highly toxic venom and the recognition of two subspecies, no molecular studies have characterized range-wide genetic diversity and population structure or tested species limits within C. scutulatus. We used mitochondrial DNA and thousands of nuclear loci from double-digest restriction site associated DNA sequencing to infer population genetic structure throughout the range of C. scutulatus, and to evaluate divergence times and gene flow between populations. We find strong support for several divergent mitochondrial and nuclear clades of C. scutulatus, including splits coincident with two major phylogeographic barriers: the Continental Divide and the elevational increase associated with the Central Mexican Plateau. We apply Bayesian clustering, phylogenetic inference, and coalescent-based species delimitation to our nuclear genetic data to test hypotheses of population structure. We also performed demographic analyses to test hypotheses relating to population divergence and gene flow. Collectively, our results support the existence of four distinct lineages within C. scutulatus, and genetically defined populations do not correspond with currently recognized subspecies ranges. Finally, we use approximate Bayesian computation to test hypotheses of divergence among multiple rattlesnake species groups distributed across the Continental Divide, and find evidence for co-divergence at this boundary during the mid-Pleistocene.}, } @article {pmid29902573, year = {2018}, author = {Capurucho, JMG and Ashley, MV and Ribas, CC and Bates, JM}, title = {Connecting Amazonian, Cerrado, and Atlantic forest histories: Paraphyly, old divergences, and modern population dynamics in tyrant-manakins (Neopelma/Tyranneutes, Aves: Pipridae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {696-705}, doi = {10.1016/j.ympev.2018.06.015}, pmid = {29902573}, issn = {1095-9513}, abstract = {Several biogeographic hypotheses have been proposed to explain connections between Amazonian and Atlantic forest biotas. These hypotheses are related to the timing of the connections and their geographic patterns. We performed a phylogeographic investigation of Tyrant-manakins (Aves: Pipridae, Neopelma/Tyranneutes) which include species inhabiting the Amazon and Atlantic forests, as well as gallery forests of the Cerrado. Using DNA sequence data, we determined phylogenetic relationships, temporal and geographic patterns of diversification, and recent intraspecific population genetic patterns, relative to the history of these biomes. We found Neopelma to be a paraphyletic genus, as N. chrysolophum is sister to Neopelma + Tyranneutes, with an estimated divergence of approximately 18 Myrs BP, within the oldest estimated divergence times of other Amazonian and Atlantic forest avian taxa. Subsequent divergences in the group occurred from Mid Miocene to Early Pliocene and involved mainly the Amazonian species, with an expansion into and subsequent speciation in the Cerrado gallery forests by N. pallescens. We found additional structure within N. chrysocephalum and N. sulphureiventer. Analysis of recent population dynamics in N. chrysocephalum, N. sulphureiventer, and N. pallescens revealed recent demographic fluctuations and restrictions to gene flow related to environmental changes since the last glacial cycle. No genetic structure was detected across the Amazon River in N. pallescens. The tyrant-manakins represent an old historical connection between the Amazon and Atlantic Forest.}, } @article {pmid29902572, year = {2018}, author = {Kawahara, AY and Breinholt, JW and Espeland, M and Storer, C and Plotkin, D and Dexter, KM and Toussaint, EFA and St Laurent, RA and Brehm, G and Vargas, S and Forero, D and Pierce, NE and Lohman, DJ}, title = {Phylogenetics of moth-like butterflies (Papilionoidea: Hedylidae) based on a new 13-locus target capture probe set.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {600-605}, doi = {10.1016/j.ympev.2018.06.002}, pmid = {29902572}, issn = {1095-9513}, abstract = {The Neotropical moth-like butterflies (Hedylidae) are perhaps the most unusual butterfly family. In addition to being species-poor, this family is predominantly nocturnal and has anti-bat ultrasound hearing organs. Evolutionary relationships among the 36 described species are largely unexplored. A new, target capture, anchored hybrid enrichment probe set ('BUTTERFLY2.0') was developed to infer relationships of hedylids and some of their butterfly relatives. The probe set includes 13 genes that have historically been used in butterfly phylogenetics. Our dataset comprised of up to 10,898 aligned base pairs from 22 hedylid species and 19 outgroups. Eleven of the thirteen loci were successfully captured from all samples, and the remaining loci were captured from ≥94% of samples. The inferred phylogeny was consistent with recent molecular studies by placing Hedylidae sister to Hesperiidae, and the tree had robust support for 80% of nodes. Our results are also consistent with morphological studies, with Macrosoma tipulata as the sister species to all remaining hedylids, followed by M. semiermis sister to the remaining species in the genus. We tested the hypothesis that nocturnality evolved once from diurnality in Hedylidae, and demonstrate that the ancestral condition was likely diurnal, with a shift to nocturnality early in the diversification of this family. The BUTTERFLY2.0 probe set includes standard butterfly phylogenetics markers, captures sequences from decades-old museum specimens, and is a cost-effective technique to infer phylogenetic relationships of the butterfly tree of life.}, } @article {pmid29901729, year = {2018}, author = {Nash, MV and Anesio, AM and Barker, G and Tranter, M and Varliero, G and Eloe-Fadrosh, EA and Nielsen, T and Turpin-Jelfs, T and Benning, LG and Sánchez-Baracaldo, P}, title = {Metagenomic insights into diazotrophic communities across Arctic glacier forefields.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, pmid = {29901729}, issn = {1574-6941}, abstract = {Microbial nitrogen fixation is crucial for building labile nitrogen stocks and facilitating higher plant colonisation in oligotrophic glacier forefield soils. Here, the diazotrophic bacterial community structure across four Arctic glacier forefields was investigated using metagenomic analysis. In total, 70 soil metagenomes were used for taxonomic interpretation based on 185 nitrogenase (nif) sequences, extracted from assembled contigs. The low number of recovered genes highlights the need for deeper sequencing in some diverse samples, to uncover the complete microbial populations. A key group of forefield diazotrophs, found throughout the forefields, was identified using a nifH phylogeny, associated with nifH Cluster I and III. Sequences related most closely to groups including Alphaproteobacteria, Betaproteobacteria, Cyanobacteria and Firmicutes. Using multiple nif genes in a Last Common Ancestor analysis revealed a diverse range of diazotrophs across the forefields. Key organisms identified across the forefields included Nostoc, Geobacter, Polaromonas and Frankia. Nitrogen fixers that are symbiotic with plants were also identified, through the presence of root associated diazotrophs, which fix nitrogen in return for reduced carbon. Additional nitrogen fixers identified in forefield soils were metabolically diverse, including fermentative and sulphur cycling bacteria, halophiles and anaerobes.}, } @article {pmid29901717, year = {2018}, author = {Morata, J and Tormo, M and Alexiou, KG and Vives, C and Ramos-Onsins, SE and Garcia-Mas, J and Casacuberta, JM}, title = {The Evolutionary Consequences of Transposon-Related Pericentromer Expansion in Melon.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1584-1595}, pmid = {29901717}, issn = {1759-6653}, mesh = {Chromosomes, Plant/genetics ; Cucurbitaceae/*genetics ; DNA Transposable Elements/*genetics ; Evolution, Molecular ; Genetic Variation/genetics ; Genome Size/genetics ; Genome, Plant/*genetics ; }, abstract = {Transposable elements (TEs) are a major driver of plant genome evolution. A part from being a rich source of new genes and regulatory sequences, TEs can also affect plant genome evolution by modifying genome size and shaping chromosome structure. TEs tend to concentrate in heterochromatic pericentromeric regions and their proliferation may expand these regions. Here, we show that after the split of melon and cucumber, TEs have expanded the pericentromeric regions of melon chromosomes that, probably as a consequence, show a very low recombination frequency. In contrast, TEs have not proliferated to a high extent in cucumber, which has small TE-dense pericentromeric regions and shows a relatively constant recombination rate along chromosomes. These differences in chromosome structure also translate in differences in gene nucleotide diversity. Although gene nucleotide diversity is essentially constant along cucumber chromosomes, melon chromosomes show a bimodal pattern of genetic variability, with a gene-poor region where variability is negatively correlated with gene density. Interestingly, genes are not homogeneously distributed in melon, and the high variable low-recombining pericentromeric regions show a higher concentration of melon-specific genes whereas genes shared with cucumber and other plants are essentially found in gene-rich chromosomal arms. The results presented here suggest that melon pericentromeric regions may allow gene sequences to evolve more freely than in other chromosomal compartments which may allow new ORFs to arise and eventually be selected. These results show that TEs can drastically change the structure of chromosomes creating different chromosomal compartments imposing different constraints for gene evolution.}, } @article {pmid29901706, year = {2018}, author = {Braun, MS and Sporer, F and Zimmermann, S and Wink, M}, title = {Birds, feather-degrading bacteria and preen glands: the antimicrobial activity of preen gland secretions from turkeys (Meleagris gallopavo) is amplified by keratinase.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy117}, pmid = {29901706}, issn = {1574-6941}, abstract = {The function of uropygial glands (preen glands) has been subject to controversial debates. In this study, we evaluated the antimicrobial potential of preen gland secretions of turkeys (Meleagris gallopavo) against 18 microbial strains by means of diffusion tests, broth microdilutions, checkerboard assays and time-kill curves. Furthermore, we tested the hypothesis that lipids exert direct antimicrobial effects on pathogens. Moreover, we checked for mutualistic relationships between the preen gland bacterium Corynebacterium uropygiale with its hosts. We found that preen gland secretions significantly inhibited the growth of a broad spectrum of bacteria and fungi, particularly when combined with keratinase. Combinations effectively killed multidrug resistant microorganisms in a strongly synergistic manner. Since feather-degrading microorganisms (FDM) express keratinase and thereby disrupt the integrity of the plumage, our data suggests that preen gland secretions of turkeys are specifically activated in the presence of FDM, and specifically eliminate FDM from feathers. However, antimicrobial effects did not originate from lipids, but were mediated by highly polar compounds which might be antimicrobial peptides (AMPs). Finally, C. uropygiale is apparently not involved in the antimicrobial activity of preen gland secretions of turkeys. In conclusion, our results suggest that turkeys can antagonize FDM by amplifying the antimicrobial properties of their preen gland secretions.}, } @article {pmid29901277, year = {2018}, author = {Holland-Moritz, H and Stuart, J and Lewis, LR and Miller, S and Mack, MC and McDaniel, SF and Fierer, N}, title = {Novel bacterial lineages associated with boreal moss species.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2625-2638}, doi = {10.1111/1462-2920.14288}, pmid = {29901277}, issn = {1462-2920}, abstract = {Mosses are critical components of boreal ecosystems where they typically account for a large proportion of net primary productivity and harbour diverse bacterial communities that can be the major source of biologically-fixed nitrogen in these ecosystems. Despite their ecological importance, we have limited understanding of how microbial communities vary across boreal moss species and the extent to which local site conditions may influence the composition of these bacterial communities. We used marker gene sequencing to analyze bacterial communities associated with seven boreal moss species collected near Fairbanks, AK, USA. We found that host identity was more important than site in determining bacterial community composition and that mosses harbour diverse lineages of potential N2 -fixers as well as an abundance of novel taxa assigned to understudied bacterial phyla (including candidate phylum WPS-2). We performed shotgun metagenomic sequencing to assemble genomes from the WPS-2 candidate phylum and found that these moss-associated bacteria are likely anoxygenic phototrophs capable of carbon fixation via RuBisCo with an ability to utilize byproducts of photorespiration from hosts via a glyoxylate shunt. These results give new insights into the metabolic capabilities of understudied bacterial lineages that associate with mosses and the importance of plant hosts in shaping their microbiomes.}, } @article {pmid29901274, year = {2018}, author = {Chen, Y and Zheng, S and Ju, Z and Zhang, C and Tang, G and Wang, J and Wen, Z and Chen, W and Ma, Z}, title = {Contribution of peroxisomal docking machinery to mycotoxin biosynthesis, pathogenicity and pexophagy in the plant pathogenic fungus Fusarium graminearum.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3224-3245}, doi = {10.1111/1462-2920.14291}, pmid = {29901274}, issn = {1462-2920}, support = {31672064//National Natural Science Foundation of China/ ; 31525020//National Natural Science Foundation of China/ ; LR17C140001//Natural Science Foundation of Zhejiang Province/ ; 2016YFE0112900//International Science & Technology Cooperation Program of China/ ; 2016YFD0300706//National Key Research and Development Program of China/ ; 31701744//National Natural Science Foundation of China/ ; CARS-3-1-15//China Agriculture Research System/ ; //Young Elite Scientist Sponsorship Program/ ; }, abstract = {Peroxisomal proliferation is highly stimulated during the biosynthesis of mycotoxins and plant infection by Fusarium graminearum. Currently, the functions of the peroxisome in these cellular processes are poorly understood. In this study, we applied genetic, cell biological and biochemical analyses to investigate the functions of the peroxisomes. We constructed targeted deletion of docking machinery components, including FgPex13, FgPex14 and the filamentous fungal specific peroxin FgPex33. Our results indicated that peroxisome dysfunction resulted in a shortage of acetyl-CoA, the precursor of trichothecene biosynthesis, and subsequently decreased deoxynivalenol (DON) production. Deletion mutants of ΔFgPex13, ΔFgPex14 or ΔFgPex33 showed an increased accumulation of endogenous reactive oxygen species (ROS) and reduced phosphorylation of MAP (Mitogen-Activated Protein) kinase FgMgv1. In addition, mutants of the docking peroxin exhibited increased sensitivity toward host oxidative bursts and cell wall integrity stress agents and reduced virulence on host plants. More importantly, we found for the first time that FgPex14 is required for pexophagy in F. graminearum. Overall, our study suggests that peroxisomes play critical roles in DON biosynthesis and virulence in F. graminearum.}, } @article {pmid29901273, year = {2018}, author = {Seo, H and Kim, KJ}, title = {Structural insight into molecular mechanism of cytokinin activating protein from Pseudomonas aeruginosa PAO1.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3214-3223}, doi = {10.1111/1462-2920.14287}, pmid = {29901273}, issn = {1462-2920}, support = {//National Research Foundation of Korea (NRF)/ ; NRF-2016M3D3A1A01913269//Ministry of Science and ICT/ ; //Technology Development Program/ ; //National Research Foundation (NRF)/ ; NRF-2017M1A2A2087631//Ministry of Science and ICT/ ; }, abstract = {Cytokinin (CK)-activating enzyme, called LOG, is a phosphoribohydrolase that hydrolyzes nucleotides into nucleobases and phosphoriboses. This reaction is a fascinating target for regulation of cellular active CK. However, misannotation of LOG as a lysine decarboxylase and the lack of detailed catalytic and substrate-binding mechanisms have prevented studies of LOG at a protein-level. In this study, we determined the crystal structure of PA4923 from Pseudomonas aeruginosa PAO1. The overall structure of PA4923 resembles those of type-I LOGs, and it exhibited phosphoribohydrolase activity against AMP. These observations indicated that PA4923 functions as an LOG. We also determined the PaLOG structure in complex with AMP and elucidated the detailed binding mode of LOG against the AMP substrate. Interestingly, PaLOG undergoes an open/closed conformational change upon binding AMP, during which the Glu74 residue located on the β3-β4 connecting loop flips 180° and moves 13 Å towards the AMP molecule. Structural and amino acid sequence comparisons of LOGs suggest that this conformational change upon substrate binding might be a common phenomenon in LOGs. In addition, based on our structural studies and the reported catalytic mechanism of nucleoside hydrolases, we proposed a catalytic mechanism for LOG in which an oxocarbenium ion-like transition state is formed.}, } @article {pmid29901272, year = {2018}, author = {Lai, JL and Tang, DJ and Liang, YW and Zhang, R and Chen, Q and Qin, ZP and Ming, ZH and Tang, JL}, title = {The RNA chaperone Hfq is important for the virulence, motility and stress tolerance in the phytopathogen Xanthomonas campestris.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {542-554}, doi = {10.1111/1758-2229.12657}, pmid = {29901272}, issn = {1758-2229}, abstract = {The RNA chaperone, Hfq, is known to play extensive roles in bacterial growth and development. More recently, it has been shown to be required for virulence in many human and animal bacterial pathogens. Despite these studies little is known about the role Hfq plays in phytopathogenic bacteria. In this study, we show Hfq is required for full virulence of the crucifer black rot pathogen Xanthomonas campestris pv. campestris (Xcc). We demonstrate that an Xcc hfq deletion strain is highly attenuated for virulence in Chinese radish and shows a severe defect in the production of virulence factors including extracellular enzymes and extracellular polysaccharide. Furthermore, the Xcc strain lacking Hfq had significantly reduced cell motility and stress tolerance. These findings suggest that Hfq is a key regulator of important aspects of virulence and adaptation of Xcc. Taken together, our findings are suggestive of a regulatory network placing Hfq at the centre of virulence gene expression control in Xcc.}, } @article {pmid29901262, year = {2018}, author = {Pettis, GS}, title = {Spreading the news about the novel conjugation mechanism in Streptomyces bacteria.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {503-510}, doi = {10.1111/1758-2229.12659}, pmid = {29901262}, issn = {1758-2229}, abstract = {The hallmark of mycelial spore-forming bacteria of the genus Streptomyces is their prolific production of antibiotics and other bioactive secondary metabolites as part of a complex morphological and physiological developmental program. They are further distinguished by a conjugation mechanism that differs substantially from the single-strand mode of DNA transfer via Type IV secretion, which is exhibited by numerous unicellular Gram-negative and Gram-positive bacteria. At the crux of the novel intermycelial transfer event in Streptomyces spp. is a membrane pore composed of a single plasmid protein (TraB), which also functions as an FtsK-like DNA pump driven by the energy of ATP hydrolysis. TraB binds to specific 8-mer repeats within the non-coding clt plasmid transfer locus and the DNA is then translocated intercellularly in double-strand form. TraB also translocates chromosomal DNA most likely by binding to 8-mer clc sequences (clt-like chromosomal sequences) distributed throughout streptomycete chromosomes. In the recipient, plasmids are dispersed through septal crosswalls apparently by a multiprotein complex comprising TraB and plasmid Spd proteins. Continued rounds of such intramycelial spreading distribute plasmids well beyond the initial entrance point during the time prior to cell differentiation and sporulation.}, } @article {pmid29901260, year = {2018}, author = {Iguchi, H and Yoshida, Y and Fujisawa, K and Taga, H and Yurimoto, H and Oyama, T and Sakai, Y}, title = {KaiC family proteins integratively control temperature-dependent UV resistance in Methylobacterium extorquens AM1.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {634-643}, doi = {10.1111/1758-2229.12662}, pmid = {29901260}, issn = {1758-2229}, abstract = {KaiC protein is the pivotal component of the circadian clock in cyanobacteria. While KaiC family proteins are well-conserved throughout divergent phylogenetic lineages, studies of the physiological roles of KaiC proteins from other microorganisms have been limited. We examined the role of the KaiC proteins, KaiC1 and KaiC2, in the methanol-utilizing bacterium Methylobacterium extorquens AM1. Wild-type M. extorquens AM1 cells exhibited temperature-dependent UV resistance (TDR) under permissive growth temperatures (24 °C -32 °C). Both the phosphorylation of KaiC2 and the intracellular levels of KaiC1 were temperature-dependent, and the TDR phenotype was positively regulated by KaiC1 and negatively regulated by KaiC2. Taken together with biochemical and functional analogies to the KaiC protein of cyanobacteria, our present results suggest that KaiC family proteins function to integrate environmental cues, that is, temperature and UV light, and output appropriate cellular responses to allow cells to adapt to changing environmental conditions.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid29901256, year = {2018}, author = {Zhang, L and Shi, N and Fan, J and Wang, F and George, TS and Feng, G}, title = {Arbuscular mycorrhizal fungi stimulate organic phosphate mobilization associated with changing bacterial community structure under field conditions.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2639-2651}, doi = {10.1111/1462-2920.14289}, pmid = {29901256}, issn = {1462-2920}, abstract = {The extraradical hyphae of arbuscular mycorrhizal fungi (AMF) harbour and interact with a microbial community performing multiple functions. However, how the AMF-microbiome interaction influences the phosphorus (P) acquisition efficiency of the mycorrhizal pathway is unclear. Here we investigated whether AMF and their hyphal microbiome play a role in promoting organic phosphorus (P) mineralizing under field conditions. We developed an AMF hyphae in-growth core system for the field using PVC tubes sealed with membrane with different size of pores (30 or 0.45 μm) to allow or deny AMF hyphae access to a patch of organic P in root-free soil. AMF and their hyphae associated microbiome played a role in enhancing soil organic P mineralization in situ in the field, which was shown to be a function of the change in bacteria community on the hyphae surface. The bacterial communities attached to the AMF hyphae surface were significantly different from those in the bulk soil. Importantly, AMF hyphae recruited bacteria that produced alkaline phosphatase and provided a function that was absent from the hyphae. These results demonstrate the importance of understanding trophic interactions to be able to gain insight into the functional controls of nutrient cycles in the rhizosphere.}, } @article {pmid29899660, year = {2018}, author = {Zhang, C and Ni, P and Ahmad, HI and Gemingguli, M and Baizilaitibei, A and Gulibaheti, D and Fang, Y and Wang, H and Asif, AR and Xiao, C and Chen, J and Ma, Y and Liu, X and Du, X and Zhao, S}, title = {Detecting the Population Structure and Scanning for Signatures of Selection in Horses (Equus caballus) From Whole-Genome Sequencing Data.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318775106}, pmid = {29899660}, issn = {1176-9343}, abstract = {Animal domestication gives rise to gradual changes at the genomic level through selection in populations. Selective sweeps have been traced in the genomes of many animal species, including humans, cattle, and dogs. However, little is known regarding positional candidate genes and genomic regions that exhibit signatures of selection in domestic horses. In addition, an understanding of the genetic processes underlying horse domestication, especially the origin of Chinese native populations, is still lacking. In our study, we generated whole genome sequences from 4 Chinese native horses and combined them with 48 publicly available full genome sequences, from which 15 341 213 high-quality unique single-nucleotide polymorphism variants were identified. Kazakh and Lichuan horses are 2 typical Asian native breeds that were formed in Kazakh or Northwest China and South China, respectively. We detected 1390 loss-of-function (LoF) variants in protein-coding genes, and gene ontology (GO) enrichment analysis revealed that some LoF-affected genes were overrepresented in GO terms related to the immune response. Bayesian clustering, distance analysis, and principal component analysis demonstrated that the population structure of these breeds largely reflected weak geographic patterns. Kazakh and Lichuan horses were assigned to the same lineage with other Asian native breeds, in agreement with previous studies on the genetic origin of Chinese domestic horses. We applied the composite likelihood ratio method to scan for genomic regions showing signals of recent selection in the horse genome. A total of 1052 genomic windows of 10 kB, corresponding to 933 distinct core regions, significantly exceeded neutral simulations. The GO enrichment analysis revealed that the genes under selective sweeps were overrepresented with GO terms, including "negative regulation of canonical Wnt signaling pathway," "muscle contraction," and "axon guidance." Frequent exercise training in domestic horses may have resulted in changes in the expression of genes related to metabolism, muscle structure, and the nervous system.}, } @article {pmid29899659, year = {2018}, author = {Vu, HT and Huynh, P and Tran, HD and Le, L}, title = {In Silico Study on Molecular Sequences for Identification of Paphiopedilum Species.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318774542}, pmid = {29899659}, issn = {1176-9343}, abstract = {Our study searched all available sequences of Paphiopedilum from NCBI (National Center for Biotechnology Information) and tested for their species resolution capability in single as well as in combination forms. A total of 28 loci were applied for analyses in the study. From the nuclear genome, the highest resolution was of LFY, followed by ACO, DEF4, and RAD51. These 4 loci were found to be even better than the popular region ITS for Paphiopedilum identification. Among the chloroplast regions, the intergenic spacer atpB-rbcL gave the highest species resolution (76.7%), followed by matK, trnL, rpoC2, and ycf1. The divergence of CHS, XDH, 18S, Nad1, ccsA, rbcL, and ycf2 was very low and should not be used as identifying markers for Paphiopedilum. In addition, 2-locus combinations could improve significantly the resolving capability for the genus, in which 14/36 data sets could be resolved completely (100%) with interspecies relationships. The indel information was also effective supporting data for molecular discrimination of species.}, } @article {pmid29899658, year = {2018}, author = {Carvalho, DS and Schnable, JC and Almeida, AMR}, title = {Integrating Phylogenetic and Network Approaches to Study Gene Family Evolution: The Case of the AGAMOUS Family of Floral Genes.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318764683}, pmid = {29899658}, issn = {1176-9343}, abstract = {The study of gene family evolution has benefited from the use of phylogenetic tools, which can greatly inform studies of both relationships within gene families and functional divergence. Here, we propose the use of a network-based approach that in combination with phylogenetic methods can provide additional support for models of gene family evolution. We dissect the contributions of each method to the improved understanding of relationships and functions within the well-characterized family of AGAMOUS floral development genes. The results obtained with the two methods largely agreed with one another. In particular, we show how network approaches can provide improved interpretations of branches with low support in a conventional gene tree. The network approach used here may also better reflect known and suspected patterns of functional divergence relative to phylogenetic methods. Overall, we believe that the combined use of phylogenetic and network tools provide a more robust assessment of gene family evolution.}, } @article {pmid29899495, year = {2018}, author = {}, title = {Wild-horse spat, astronaut minister and record flooding.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {166-167}, doi = {10.1038/d41586-018-05370-z}, pmid = {29899495}, issn = {1476-4687}, } @article {pmid29899494, year = {2018}, author = {}, title = {Reform the Antarctic Treaty.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {161}, doi = {10.1038/d41586-018-05368-7}, pmid = {29899494}, issn = {1476-4687}, mesh = {Antarctic Regions ; Ecosystem ; *Fisheries ; *International Cooperation ; Oceans and Seas ; }, } @article {pmid29899493, year = {2018}, author = {Brooks, CM and Ainley, DG and Abrams, PA and Dayton, PK and Hofman, RJ and Jacquet, J and Siniff, DB}, title = {Antarctic fisheries: factor climate change into their management.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {177-180}, doi = {10.1038/d41586-018-05372-x}, pmid = {29899493}, issn = {1476-4687}, mesh = {Animals ; Antarctic Regions ; Aquatic Organisms ; Biodiversity ; *Climate Change ; Conservation of Natural Resources/economics/*legislation & jurisprudence/trends ; Endangered Species/economics/legislation & jurisprudence ; Environmental Policy/economics/*legislation & jurisprudence/trends ; Fisheries/economics/*legislation & jurisprudence/*organization & administration ; Fishes/classification/physiology ; Food Chain ; Oceans and Seas ; Whales ; Wilderness ; }, } @article {pmid29899492, year = {2018}, author = {Chown, SL}, title = {Polar collaborations are key to successful policies.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {163}, doi = {10.1038/d41586-018-05369-6}, pmid = {29899492}, issn = {1476-4687}, mesh = {Animals ; Antarctic Regions ; Climate Change ; Conservation of Natural Resources/legislation & jurisprudence ; Environmental Policy/*legislation & jurisprudence ; International Cooperation/*legislation & jurisprudence ; Mining/legislation & jurisprudence ; Research/*legislation & jurisprudence/organization & administration ; }, } @article {pmid29899491, year = {2018}, author = {Cartlidge, E}, title = {The elemental fight behind the periodic table's latest additions.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {175-176}, doi = {10.1038/d41586-018-05371-y}, pmid = {29899491}, issn = {1476-4687}, } @article {pmid29899490, year = {2018}, author = {Laurat, J}, title = {On-demand entanglement could lead to scalable quantum networks.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {192-193}, doi = {10.1038/d41586-018-05336-1}, pmid = {29899490}, issn = {1476-4687}, mesh = {*Computer Simulation ; *Quantum Theory ; }, } @article {pmid29899489, year = {2018}, author = {Bonfoh, B and Saric, J and Utzinger, J}, title = {Research hotspots in Côte d'Ivoire.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {189}, doi = {10.1038/d41586-018-05413-5}, pmid = {29899489}, issn = {1476-4687}, mesh = {Cote d'Ivoire ; *Research ; }, } @article {pmid29899488, year = {2018}, author = {Rhodes, R}, title = {Pioneering women in energy physics.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {189}, doi = {10.1038/d41586-018-05391-8}, pmid = {29899488}, issn = {1476-4687}, } @article {pmid29899487, year = {2018}, author = {Binning, SA and Jutfelt, F and Sundin, J}, title = {Exorcise citations to the 'living dead' from the literature.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {189}, doi = {10.1038/d41586-018-05386-5}, pmid = {29899487}, issn = {1476-4687}, mesh = {Bibliometrics ; Databases, Factual ; Publishing/*standards ; Research/*standards ; *Retraction of Publication as Topic ; }, } @article {pmid29899486, year = {2018}, author = {Knoppers, B}, title = {Broaden human-rights focus for health data under GDPR.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {189}, doi = {10.1038/d41586-018-05388-3}, pmid = {29899486}, issn = {1476-4687}, mesh = {*Computer Security ; *Human Rights ; Humans ; }, } @article {pmid29899485, year = {2018}, author = {Miclăuș, M and Micu, O}, title = {Hurdles to international review scupper science in Romania.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {189}, doi = {10.1038/d41586-018-05390-9}, pmid = {29899485}, issn = {1476-4687}, mesh = {Communication Barriers ; European Union/economics ; Gross Domestic Product ; *Internationality ; *Peer Review, Research ; Romania ; Science/economics/*standards ; }, } @article {pmid29899483, year = {2018}, author = {Shakun, JD and Corbett, LB and Bierman, PR and Underwood, K and Rizzo, DM and Zimmerman, SR and Caffee, MW and Naish, T and Golledge, NR and Hay, CC}, title = {Minimal East Antarctic Ice Sheet retreat onto land during the past eight million years.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {284-287}, doi = {10.1038/s41586-018-0155-6}, pmid = {29899483}, issn = {1476-4687}, abstract = {The East Antarctic Ice Sheet (EAIS) is the largest potential contributor to sea-level rise. However, efforts to predict the future evolution of the EAIS are hindered by uncertainty in how it responded to past warm periods, for example, during the Pliocene epoch (5.3 to 2.6 million years ago), when atmospheric carbon dioxide concentrations were last higher than 400 parts per million. Geological evidence indicates that some marine-based portions of the EAIS and the West Antarctic Ice Sheet retreated during parts of the Pliocene1,2, but it remains unclear whether ice grounded above sea level also experienced retreat. This uncertainty persists because global sea-level estimates for the Pliocene have large uncertainties and cannot be used to rule out substantial terrestrial ice loss 3 , and also because direct geological evidence bearing on past ice retreat on land is lacking. Here we show that land-based sectors of the EAIS that drain into the Ross Sea have been stable throughout the past eight million years. We base this conclusion on the extremely low concentrations of cosmogenic 10Be and 26Al isotopes found in quartz sand extracted from a land-proximal marine sediment core. This sediment had been eroded from the continent, and its low levels of cosmogenic nuclides indicate that it experienced only minimal exposure to cosmic radiation, suggesting that the sediment source regions were covered in ice. These findings indicate that atmospheric warming during the past eight million years was insufficient to cause widespread or long-lasting meltback of the EAIS margin onto land. We suggest that variations in Antarctic ice volume in response to the range of global temperatures experienced over this period-up to 2-3 degrees Celsius above preindustrial temperatures 4 , corresponding to future scenarios involving carbon dioxide concentrations of between 400 and 500 parts per million-were instead driven mostly by the retreat of marine ice margins, in agreement with the latest models5,6.}, } @article {pmid29899482, year = {2018}, author = {, }, title = {Mass balance of the Antarctic Ice Sheet from 1992 to 2017.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {219-222}, doi = {10.1038/s41586-018-0179-y}, pmid = {29899482}, issn = {1476-4687}, abstract = {The Antarctic Ice Sheet is an important indicator of climate change and driver of sea-level rise. Here we combine satellite observations of its changing volume, flow and gravitational attraction with modelling of its surface mass balance to show that it lost 2,720 ± 1,390 billion tonnes of ice between 1992 and 2017, which corresponds to an increase in mean sea level of 7.6 ± 3.9 millimetres (errors are one standard deviation). Over this period, ocean-driven melting has caused rates of ice loss from West Antarctica to increase from 53 ± 29 billion to 159 ± 26 billion tonnes per year; ice-shelf collapse has increased the rate of ice loss from the Antarctic Peninsula from 7 ± 13 billion to 33 ± 16 billion tonnes per year. We find large variations in and among model estimates of surface mass balance and glacial isostatic adjustment for East Antarctica, with its average rate of mass gain over the period 1992-2017 (5 ± 46 billion tonnes per year) being the least certain.}, } @article {pmid29899481, year = {2018}, author = {Rintoul, SR and Chown, SL and DeConto, RM and England, MH and Fricker, HA and Masson-Delmotte, V and Naish, TR and Siegert, MJ and Xavier, JC}, title = {Choosing the future of Antarctica.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {233-241}, doi = {10.1038/s41586-018-0173-4}, pmid = {29899481}, issn = {1476-4687}, mesh = {Animals ; Antarctic Regions ; Atmosphere/chemistry ; Biodiversity ; Carbon Dioxide/analysis ; Fisheries ; Food Chain ; Global Warming/*prevention & control/*statistics & numerical data ; Human Activities ; Ice Cover/chemistry ; Introduced Species ; Seawater/analysis ; Time Factors ; }, abstract = {We present two narratives on the future of Antarctica and the Southern Ocean, from the perspective of an observer looking back from 2070. In the first scenario, greenhouse gas emissions remained unchecked, the climate continued to warm, and the policy response was ineffective; this had large ramifications in Antarctica and the Southern Ocean, with worldwide impacts. In the second scenario, ambitious action was taken to limit greenhouse gas emissions and to establish policies that reduced anthropogenic pressure on the environment, slowing the rate of change in Antarctica. Choices made in the next decade will determine what trajectory is realized.}, } @article {pmid29899480, year = {2018}, author = {Shepherd, A and Fricker, HA and Farrell, SL}, title = {Trends and connections across the Antarctic cryosphere.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {223-232}, doi = {10.1038/s41586-018-0171-6}, pmid = {29899480}, issn = {1476-4687}, mesh = {Antarctic Regions ; Ecosystem ; *Ice Cover ; Lakes ; Motion ; Oceans and Seas ; Satellite Imagery ; }, abstract = {Satellite observations have transformed our understanding of the Antarctic cryosphere. The continent holds the vast majority of Earth's fresh water, and blankets swathes of the Southern Hemisphere in ice. Reductions in the thickness and extent of floating ice shelves have disturbed inland ice, triggering retreat, acceleration and drawdown of marine-terminating glaciers. The waxing and waning of Antarctic sea ice is one of Earth's greatest seasonal habitat changes, and although the maximum extent of the sea ice has increased modestly since the 1970s, inter-annual variability is high, and there is evidence of longer-term decline in its extent.}, } @article {pmid29899479, year = {2018}, author = {Brook, EJ and Buizert, C}, title = {Antarctic and global climate history viewed from ice cores.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {200-208}, doi = {10.1038/s41586-018-0172-5}, pmid = {29899479}, issn = {1476-4687}, abstract = {A growing network of ice cores reveals the past 800,000 years of Antarctic climate and atmospheric composition. The data show tight links among greenhouse gases, aerosols and global climate on many timescales, demonstrate connections between Antarctica and distant locations, and reveal the extraordinary differences between the composition of our present atmosphere and its natural range of variability as revealed in the ice core record. Further coring in extremely challenging locations is now being planned, with the goal of finding older ice and resolving the mechanisms underlying the shift of glacial cycles from 40,000-year to 100,000-year cycles about a million years ago, one of the great mysteries of climate science.}, } @article {pmid29899478, year = {2018}, author = {Kurpiers, P and Magnard, P and Walter, T and Royer, B and Pechal, M and Heinsoo, J and Salathé, Y and Akin, A and Storz, S and Besse, JC and Gasparinetti, S and Blais, A and Wallraff, A}, title = {Deterministic quantum state transfer and remote entanglement using microwave photons.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {264-267}, doi = {10.1038/s41586-018-0195-y}, pmid = {29899478}, issn = {1476-4687}, abstract = {Sharing information coherently between nodes of a quantum network is fundamental to distributed quantum information processing. In this scheme, the computation is divided into subroutines and performed on several smaller quantum registers that are connected by classical and quantum channels 1 . A direct quantum channel, which connects nodes deterministically rather than probabilistically, achieves larger entanglement rates between nodes and is advantageous for distributed fault-tolerant quantum computation 2 . Here we implement deterministic state-transfer and entanglement protocols between two superconducting qubits fabricated on separate chips. Superconducting circuits 3 constitute a universal quantum node 4 that is capable of sending, receiving, storing and processing quantum information5-8. Our implementation is based on an all-microwave cavity-assisted Raman process 9 , which entangles or transfers the qubit state of a transmon-type artificial atom 10 with a time-symmetric itinerant single photon. We transfer qubit states by absorbing these itinerant photons at the receiving node, with a probability of 98.1 ± 0.1 per cent, achieving a transfer-process fidelity of 80.02 ± 0.07 per cent for a protocol duration of only 180 nanoseconds. We also prepare remote entanglement on demand with a fidelity as high as 78.9 ± 0.1 per cent at a rate of 50 kilohertz. Our results are in excellent agreement with numerical simulations based on a master-equation description of the system. This deterministic protocol has the potential to be used for quantum computing distributed across different nodes of a cryogenic network.}, } @article {pmid29899477, year = {2018}, author = {Neugebohren, J and Borodin, D and Hahn, HW and Altschäffel, J and Kandratsenka, A and Auerbach, DJ and Campbell, CT and Schwarzer, D and Harding, DJ and Wodtke, AM and Kitsopoulos, TN}, title = {Velocity-resolved kinetics of site-specific carbon monoxide oxidation on platinum surfaces.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {280-283}, doi = {10.1038/s41586-018-0188-x}, pmid = {29899477}, issn = {1476-4687}, abstract = {Catalysts are widely used to increase reaction rates. They function by stabilizing the transition state of the reaction at their active site, where the atomic arrangement ensures favourable interactions 1 . However, mechanistic understanding is often limited when catalysts possess multiple active sites-such as sites associated with either the step edges or the close-packed terraces of inorganic nanoparticles2-4-with distinct activities that cannot be measured simultaneously. An example is the oxidation of carbon monoxide over platinum surfaces, one of the oldest and best studied heterogeneous reactions. In 1824, this reaction was recognized to be crucial for the function of the Davy safety lamp, and today it is used to optimize combustion, hydrogen production and fuel-cell operation5,6. The carbon dioxide products are formed in a bimodal kinetic energy distribution7-13; however, despite extensive study 5 , it remains unclear whether this reflects the involvement of more than one reaction mechanism occurring at multiple active sites12,13. Here we show that the reaction rates at different active sites can be measured simultaneously, using molecular beams to controllably introduce reactants and slice ion imaging14,15 to map the velocity vectors of the product molecules, which reflect the symmetry and the orientation of the active site 16 . We use this velocity-resolved kinetics approach to map the oxidation rates of carbon monoxide at step edges and terrace sites on platinum surfaces, and find that the reaction proceeds through two distinct channels11-13: it is dominated at low temperatures by the more active step sites, and at high temperatures by the more abundant terrace sites. We expect our approach to be applicable to a wide range of heterogeneous reactions and to provide improved mechanistic understanding of the contribution of different active sites, which should be useful in the design of improved catalysts.}, } @article {pmid29899476, year = {2018}, author = {Kim, Y and Yuk, H and Zhao, R and Chester, SA and Zhao, X}, title = {Printing ferromagnetic domains for untethered fast-transforming soft materials.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {274-279}, doi = {10.1038/s41586-018-0185-0}, pmid = {29899476}, issn = {1476-4687}, abstract = {Soft materials capable of transforming between three-dimensional (3D) shapes in response to stimuli such as light, heat, solvent, electric and magnetic fields have applications in diverse areas such as flexible electronics1,2, soft robotics3,4 and biomedicine5-7. In particular, magnetic fields offer a safe and effective manipulation method for biomedical applications, which typically require remote actuation in enclosed and confined spaces8-10. With advances in magnetic field control 11 , magnetically responsive soft materials have also evolved from embedding discrete magnets 12 or incorporating magnetic particles 13 into soft compounds to generating nonuniform magnetization profiles in polymeric sheets14,15. Here we report 3D printing of programmed ferromagnetic domains in soft materials that enable fast transformations between complex 3D shapes via magnetic actuation. Our approach is based on direct ink writing 16 of an elastomer composite containing ferromagnetic microparticles. By applying a magnetic field to the dispensing nozzle while printing 17 , we reorient particles along the applied field to impart patterned magnetic polarity to printed filaments. This method allows us to program ferromagnetic domains in complex 3D-printed soft materials, enabling a set of previously inaccessible modes of transformation, such as remotely controlled auxetic behaviours of mechanical metamaterials with negative Poisson's ratios. The actuation speed and power density of our printed soft materials with programmed ferromagnetic domains are orders of magnitude greater than existing 3D-printed active materials. We further demonstrate diverse functions derived from complex shape changes, including reconfigurable soft electronics, a mechanical metamaterial that can jump and a soft robot that crawls, rolls, catches fast-moving objects and transports a pharmaceutical dose.}, } @article {pmid29899475, year = {2018}, author = {Humphreys, PC and Kalb, N and Morits, JPJ and Schouten, RN and Vermeulen, RFL and Twitchen, DJ and Markham, M and Hanson, R}, title = {Deterministic delivery of remote entanglement on a quantum network.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {268-273}, doi = {10.1038/s41586-018-0200-5}, pmid = {29899475}, issn = {1476-4687}, abstract = {Large-scale quantum networks promise to enable secure communication, distributed quantum computing, enhanced sensing and fundamental tests of quantum mechanics through the distribution of entanglement across nodes1-7. Moving beyond current two-node networks8-13 requires the rate of entanglement generation between nodes to exceed the decoherence (loss) rate of the entanglement. If this criterion is met, intrinsically probabilistic entangling protocols can be used to provide deterministic remote entanglement at pre-specified times. Here we demonstrate this using diamond spin qubit nodes separated by two metres. We realize a fully heralded single-photon entanglement protocol that achieves entangling rates of up to 39 hertz, three orders of magnitude higher than previously demonstrated two-photon protocols on this platform 14 . At the same time, we suppress the decoherence rate of remote-entangled states to five hertz through dynamical decoupling. By combining these results with efficient charge-state control and mitigation of spectral diffusion, we deterministically deliver a fresh remote state with an average entanglement fidelity of more than 0.5 at every clock cycle of about 100 milliseconds without any pre- or post-selection. These results demonstrate a key building block for extended quantum networks and open the door to entanglement distribution across multiple remote nodes.}, } @article {pmid29899474, year = {2018}, author = {Rintoul, SR}, title = {The global influence of localized dynamics in the Southern Ocean.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {209-218}, doi = {10.1038/s41586-018-0182-3}, pmid = {29899474}, issn = {1476-4687}, abstract = {The circulation of the Southern Ocean connects ocean basins, links the deep and shallow layers of the ocean, and has a strong influence on global ocean circulation, climate, biogeochemical cycles and the Antarctic Ice Sheet. Processes that act on local and regional scales, which are often mediated by the interaction of the flow with topography, are fundamental in shaping the large-scale, three-dimensional circulation of the Southern Ocean. Recent advances provide insight into the response of the Southern Ocean to future change and the implications for climate, the carbon cycle and sea-level rise.}, } @article {pmid29899456, year = {2018}, author = {Kingslake, J and Scherer, RP and Albrecht, T and Coenen, J and Powell, RD and Reese, R and Stansell, ND and Tulaczyk, S and Wearing, MG and Whitehouse, PL}, title = {Extensive retreat and re-advance of the West Antarctic Ice Sheet during the Holocene.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {430-434}, doi = {10.1038/s41586-018-0208-x}, pmid = {29899456}, issn = {1476-4687}, mesh = {Antarctic Regions ; Global Warming ; History, Ancient ; *Ice Cover ; Models, Theoretical ; Radiometric Dating ; }, abstract = {To predict the future contributions of the Antarctic ice sheets to sea-level rise, numerical models use reconstructions of past ice-sheet retreat after the Last Glacial Maximum to tune model parameters 1 . Reconstructions of the West Antarctic Ice Sheet have assumed that it retreated progressively throughout the Holocene epoch (the past 11,500 years or so)2-4. Here we show, however, that over this period the grounding line of the West Antarctic Ice Sheet (which marks the point at which it is no longer in contact with the ground and becomes a floating ice shelf) retreated several hundred kilometres inland of today's grounding line, before isostatic rebound caused it to re-advance to its present position. Our evidence includes, first, radiocarbon dating of sediment cores recovered from beneath the ice streams of the Ross Sea sector, indicating widespread Holocene marine exposure; and second, ice-penetrating radar observations of englacial structure in the Weddell Sea sector, indicating ice-shelf grounding. We explore the implications of these findings with an ice-sheet model. Modelled re-advance of the grounding line in the Holocene requires ice-shelf grounding caused by isostatic rebound. Our findings overturn the assumption of progressive retreat of the grounding line during the Holocene in West Antarctica, and corroborate previous suggestions of ice-sheet re-advance 5 . Rebound-driven stabilizing processes were apparently able to halt and reverse climate-initiated ice loss. Whether these processes can reverse present-day ice loss 6 on millennial timescales will depend on bedrock topography and mantle viscosity-parameters that are difficult to measure and to incorporate into ice-sheet models.}, } @article {pmid29899455, year = {2018}, author = {Koehl, A and Hu, H and Maeda, S and Zhang, Y and Qu, Q and Paggi, JM and Latorraca, NR and Hilger, D and Dawson, R and Matile, H and Schertler, GFX and Granier, S and Weis, WI and Dror, RO and Manglik, A and Skiniotis, G and Kobilka, BK}, title = {Structure of the µ-opioid receptor-Gi protein complex.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {547-552}, doi = {10.1038/s41586-018-0219-7}, pmid = {29899455}, issn = {1476-4687}, support = {R01 GM083118/GM/NIGMS NIH HHS/United States ; R37 DA036246/DA/NIDA NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; *Cryoelectron Microscopy ; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-/pharmacology ; Female ; GTP-Binding Protein alpha Subunits, Gi-Go/chemistry/*metabolism/*ultrastructure ; GTP-Binding Protein alpha Subunits, Gs/chemistry/metabolism ; Humans ; Ligands ; Mice ; Mice, Inbred BALB C ; Molecular Dynamics Simulation ; Morphinans/chemistry/metabolism ; Protein Stability/drug effects ; Receptors, Adrenergic, beta-2/chemistry/metabolism ; Receptors, Opioid, mu/agonists/chemistry/*metabolism/*ultrastructure ; Substrate Specificity ; }, abstract = {The μ-opioid receptor (μOR) is a G-protein-coupled receptor (GPCR) and the target of most clinically and recreationally used opioids. The induced positive effects of analgesia and euphoria are mediated by μOR signalling through the adenylyl cyclase-inhibiting heterotrimeric G protein Gi. Here we present the 3.5 Å resolution cryo-electron microscopy structure of the μOR bound to the agonist peptide DAMGO and nucleotide-free Gi. DAMGO occupies the morphinan ligand pocket, with its N terminus interacting with conserved receptor residues and its C terminus engaging regions important for opioid-ligand selectivity. Comparison of the μOR-Gi complex to previously determined structures of other GPCRs bound to the stimulatory G protein Gs reveals differences in the position of transmembrane receptor helix 6 and in the interactions between the G protein α-subunit and the receptor core. Together, these results shed light on the structural features that contribute to the Gi protein-coupling specificity of the µOR.}, } @article {pmid29899454, year = {2018}, author = {Bi, S and Zheng, X and Wang, X and Cignetti, NE and Yang, S and Wible, JR}, title = {An Early Cretaceous eutherian and the placental-marsupial dichotomy.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {390-395}, doi = {10.1038/s41586-018-0210-3}, pmid = {29899454}, issn = {1476-4687}, mesh = {Animals ; China ; Eutheria/anatomy & histology/*classification ; Fossils ; Marsupialia/anatomy & histology/*classification ; *Phylogeny ; }, abstract = {Molecular estimates of the divergence of placental and marsupial mammals and their broader clades (Eutheria and Metatheria, respectively) fall primarily in the Jurassic period. Supporting these estimates, Juramaia-the oldest purported eutherian-is from the early Late Jurassic (160 million years ago) of northeastern China. Sinodelphys-the oldest purported metatherian-is from the same geographic area but is 35 million years younger, from the Jehol biota. Here we report a new Jehol eutherian, Ambolestes zhoui, with a nearly complete skeleton that preserves anatomical details that are unknown from contemporaneous mammals, including the ectotympanic and hyoid apparatus. This new fossil demonstrates that Sinodelphys is a eutherian, and that postcranial differences between Sinodelphys and the Jehol eutherian Eomaia-previously thought to indicate separate invasions of a scansorial niche by eutherians and metatherians-are instead variations among the early members of the placental lineage. The oldest known metatherians are now not from eastern Asia but are 110 million years old from western North America, which produces a 50-million-year ghost lineage for Metatheria.}, } @article {pmid29899453, year = {2018}, author = {Parua, PK and Booth, GT and Sansó, M and Benjamin, B and Tanny, JC and Lis, JT and Fisher, RP}, title = {A Cdk9-PP1 switch regulates the elongation-termination transition of RNA polymerase II.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {460-464}, pmid = {29899453}, issn = {1476-4687}, support = {R37 GM025232/GM/NIGMS NIH HHS/United States ; R01 GM104291/GM/NIGMS NIH HHS/United States ; R35 GM127289/GM/NIGMS NIH HHS/United States ; R01 GM025232/GM/NIGMS NIH HHS/United States ; P30 CA196521/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Cyclin-Dependent Kinase 9/chemistry/*metabolism ; Humans ; Mitosis ; Phosphoprotein Phosphatases/chemistry/*metabolism ; Phosphorylation ; RNA Polymerase II/chemistry/*metabolism ; Schizosaccharomyces/cytology/*enzymology/*genetics ; Schizosaccharomyces pombe Proteins/chemistry/*metabolism ; Signal Transduction ; *Transcription Elongation, Genetic ; *Transcription Termination, Genetic ; Transcriptional Elongation Factors/chemistry/metabolism ; }, abstract = {The end of the RNA polymerase II (Pol II) transcription cycle is strictly regulated to prevent interference between neighbouring genes and to safeguard transcriptome integrity 1 . The accumulation of Pol II downstream of the cleavage and polyadenylation signal can facilitate the recruitment of factors involved in mRNA 3'-end formation and termination 2 , but how this sequence is initiated remains unclear. In a chemical-genetic screen, human protein phosphatase 1 (PP1) isoforms were identified as substrates of positive transcription elongation factor b (P-TEFb), also known as the cyclin-dependent kinase 9 (Cdk9)-cyclin T1 (CycT1) complex 3 . Here we show that Cdk9 and PP1 govern phosphorylation of the conserved elongation factor Spt5 in the fission yeast Schizosaccharomyces pombe. Cdk9 phosphorylates both Spt5 and a negative regulatory site on the PP1 isoform Dis2 4 . Sites targeted by Cdk9 in the Spt5 carboxy-terminal domain can be dephosphorylated by Dis2 in vitro, and dis2 mutations retard Spt5 dephosphorylation after inhibition of Cdk9 in vivo. Chromatin immunoprecipitation and sequencing analysis indicates that Spt5 is dephosphorylated as transcription complexes traverse the cleavage and polyadenylation signal, concomitant with the accumulation of Pol II phosphorylated at residue Ser2 of the carboxy-terminal domain consensus heptad repeat 5 . A conditionally lethal Dis2-inactivating mutation attenuates the drop in Spt5 phosphorylation on chromatin, promotes transcription beyond the normal termination zone (as detected by precision run-on transcription and sequencing 6) and is genetically suppressed by the ablation of Cdk9 target sites in Spt5. These results suggest that the transition of Pol II from elongation to termination coincides with a Dis2-dependent reversal of Cdk9 signalling-a switch that is analogous to a Cdk1-PP1 circuit that controls mitotic progression 4 .}, } @article {pmid29899452, year = {2018}, author = {Venot, Q and Blanc, T and Rabia, SH and Berteloot, L and Ladraa, S and Duong, JP and Blanc, E and Johnson, SC and Hoguin, C and Boccara, O and Sarnacki, S and Boddaert, N and Pannier, S and Martinez, F and Magassa, S and Yamaguchi, J and Knebelmann, B and Merville, P and Grenier, N and Joly, D and Cormier-Daire, V and Michot, C and Bole-Feysot, C and Picard, A and Soupre, V and Lyonnet, S and Sadoine, J and Slimani, L and Chaussain, C and Laroche-Raynaud, C and Guibaud, L and Broissand, C and Amiel, J and Legendre, C and Terzi, F and Canaud, G}, title = {Targeted therapy in patients with PIK3CA-related overgrowth syndrome.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {540-546}, doi = {10.1038/s41586-018-0217-9}, pmid = {29899452}, issn = {1476-4687}, mesh = {Adult ; Animals ; Child ; Class I Phosphatidylinositol 3-Kinases/*antagonists & inhibitors/*metabolism ; Disease Models, Animal ; Female ; HeLa Cells ; Heart Failure/complications/drug therapy ; Humans ; Lipoma/*drug therapy/*enzymology ; Male ; Mice ; *Molecular Targeted Therapy ; Musculoskeletal Abnormalities/*drug therapy/*enzymology ; Nevus/*drug therapy/*enzymology ; Phenotype ; Scoliosis/complications/drug therapy ; Sirolimus/therapeutic use ; Syndrome ; Thiazoles/*therapeutic use ; Vascular Malformations/*drug therapy/*enzymology ; Vascular Neoplasms/complications/drug therapy ; }, abstract = {CLOVES syndrome (congenital lipomatous overgrowth, vascular malformations, epidermal naevi, scoliosis/skeletal and spinal syndrome) is a genetic disorder that results from somatic, mosaic gain-of-function mutations of the PIK3CA gene, and belongs to the spectrum of PIK3CA-related overgrowth syndromes (PROS). This rare condition has no specific treatment and a poor survival rate. Here, we describe a postnatal mouse model of PROS/CLOVES that partially recapitulates the human disease, and demonstrate the efficacy of BYL719, an inhibitor of PIK3CA, in preventing and improving organ dysfunction. On the basis of these results, we used BYL719 to treat nineteen patients with PROS. The drug improved the disease symptoms in all patients. Previously intractable vascular tumours became smaller, congestive heart failure was improved, hemihypertrophy was reduced, and scoliosis was attenuated. The treatment was not associated with any substantial side effects. In conclusion, this study provides the first direct evidence supporting PIK3CA inhibition as a promising therapeutic strategy in patients with PROS.}, } @article {pmid29899451, year = {2018}, author = {Wang, Z and Ma, J and Miyoshi, C and Li, Y and Sato, M and Ogawa, Y and Lou, T and Ma, C and Gao, X and Lee, C and Fujiyama, T and Yang, X and Zhou, S and Hotta-Hirashima, N and Klewe-Nebenius, D and Ikkyu, A and Kakizaki, M and Kanno, S and Cao, L and Takahashi, S and Peng, J and Yu, Y and Funato, H and Yanagisawa, M and Liu, Q}, title = {Quantitative phosphoproteomic analysis of the molecular substrates of sleep need.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {435-439}, doi = {10.1038/s41586-018-0218-8}, pmid = {29899451}, issn = {1476-4687}, support = {GM1114160/NH/NIH HHS/United States ; R01 GM111367/GM/NIGMS NIH HHS/United States ; R01 GM114160/GM/NIGMS NIH HHS/United States ; GM111367/NH/NIH HHS/United States ; R01 AG047928/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Brain/*metabolism/physiology ; Gain of Function Mutation ; *Homeostasis ; Male ; Memory Consolidation/physiology ; Mice ; Mice, Inbred C57BL ; Phosphoproteins/*analysis/*metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Proteome/*analysis/metabolism ; *Proteomics ; Sleep/*physiology ; Sleep Deprivation/metabolism/physiopathology ; Synapses/physiology ; Wakefulness/physiology ; }, abstract = {Sleep and wake have global effects on brain physiology, from molecular changes1-4 and neuronal activities to synaptic plasticity3-7. Sleep-wake homeostasis is maintained by the generation of a sleep need that accumulates during waking and dissipates during sleep8-11. Here we investigate the molecular basis of sleep need using quantitative phosphoproteomic analysis of the sleep-deprived and Sleepy mouse models of increased sleep need. Sleep deprivation induces cumulative phosphorylation of the brain proteome, which dissipates during sleep. Sleepy mice, owing to a gain-of-function mutation in the Sik3 gene 12 , have a constitutively high sleep need despite increased sleep amount. The brain proteome of these mice exhibits hyperphosphorylation, similar to that seen in the brain of sleep-deprived mice. Comparison of the two models identifies 80 mostly synaptic sleep-need-index phosphoproteins (SNIPPs), in which phosphorylation states closely parallel changes of sleep need. SLEEPY, the mutant SIK3 protein, preferentially associates with and phosphorylates SNIPPs. Inhibition of SIK3 activity reduces phosphorylation of SNIPPs and slow wave activity during non-rapid-eye-movement sleep, the best known measurable index of sleep need, in both Sleepy mice and sleep-deprived wild-type mice. Our results suggest that phosphorylation of SNIPPs accumulates and dissipates in relation to sleep need, and therefore SNIPP phosphorylation is a molecular signature of sleep need. Whereas waking encodes memories by potentiating synapses, sleep consolidates memories and restores synaptic homeostasis by globally downscaling excitatory synapses4-6. Thus, the phosphorylation-dephosphorylation cycle of SNIPPs may represent a major regulatory mechanism that underlies both synaptic homeostasis and sleep-wake homeostasis.}, } @article {pmid29899450, year = {2018}, author = {Kang, Y and Kuybeda, O and de Waal, PW and Mukherjee, S and Van Eps, N and Dutka, P and Zhou, XE and Bartesaghi, A and Erramilli, S and Morizumi, T and Gu, X and Yin, Y and Liu, P and Jiang, Y and Meng, X and Zhao, G and Melcher, K and Ernst, OP and Kossiakoff, AA and Subramaniam, S and Xu, HE}, title = {Cryo-EM structure of human rhodopsin bound to an inhibitory G protein.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {553-558}, doi = {10.1038/s41586-018-0215-y}, pmid = {29899450}, issn = {1476-4687}, support = {DK071662/NH/NIH HHS/United States ; }, mesh = {Arrestin/chemistry/metabolism ; Binding Sites ; *Cryoelectron Microscopy ; GTP-Binding Protein alpha Subunits, Gi-Go/chemistry/*metabolism/*ultrastructure ; GTP-Binding Protein alpha Subunits, Gs/chemistry/metabolism ; Humans ; Models, Molecular ; Receptors, Adrenergic, beta-2/chemistry/metabolism ; Rhodopsin/chemistry/*metabolism/*ultrastructure ; Signal Transduction ; Substrate Specificity ; }, abstract = {G-protein-coupled receptors comprise the largest family of mammalian transmembrane receptors. They mediate numerous cellular pathways by coupling with downstream signalling transducers, including the hetrotrimeric G proteins Gs (stimulatory) and Gi (inhibitory) and several arrestin proteins. The structural mechanisms that define how G-protein-coupled receptors selectively couple to a specific type of G protein or arrestin remain unknown. Here, using cryo-electron microscopy, we show that the major interactions between activated rhodopsin and Gi are mediated by the C-terminal helix of the Gi α-subunit, which is wedged into the cytoplasmic cavity of the transmembrane helix bundle and directly contacts the amino terminus of helix 8 of rhodopsin. Structural comparisons of inactive, Gi-bound and arrestin-bound forms of rhodopsin with inactive and Gs-bound forms of the β2-adrenergic receptor provide a foundation to understand the unique structural signatures that are associated with the recognition of Gs, Gi and arrestin by activated G-protein-coupled receptors.}, } @article {pmid29899449, year = {2018}, author = {Massom, RA and Scambos, TA and Bennetts, LG and Reid, P and Squire, VA and Stammerjohn, SE}, title = {Antarctic ice shelf disintegration triggered by sea ice loss and ocean swell.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {383-389}, doi = {10.1038/s41586-018-0212-1}, pmid = {29899449}, issn = {1476-4687}, abstract = {Understanding the causes of recent catastrophic ice shelf disintegrations is a crucial step towards improving coupled models of the Antarctic Ice Sheet and predicting its future state and contribution to sea-level rise. An overlooked climate-related causal factor is regional sea ice loss. Here we show that for the disintegration events observed (the collapse of the Larsen A and B and Wilkins ice shelves), the increased seasonal absence of a protective sea ice buffer enabled increased flexure of vulnerable outer ice shelf margins by ocean swells that probably weakened them to the point of calving. This outer-margin calving triggered wider-scale disintegration of ice shelves compromised by multiple factors in preceding years, with key prerequisites being extensive flooding and outer-margin fracturing. Wave-induced flexure is particularly effective in outermost ice shelf regions thinned by bottom crevassing. Our analysis of satellite and ocean-wave data and modelling of combined ice shelf, sea ice and wave properties highlights the need for ice sheet models to account for sea ice and ocean waves.}, } @article {pmid29899448, year = {2018}, author = {Kapp, FG and Perlin, JR and Hagedorn, EJ and Gansner, JM and Schwarz, DE and O'Connell, LA and Johnson, NS and Amemiya, C and Fisher, DE and Wölfle, U and Trompouki, E and Niemeyer, CM and Driever, W and Zon, LI}, title = {Protection from UV light is an evolutionarily conserved feature of the haematopoietic niche.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {445-448}, pmid = {29899448}, issn = {1476-4687}, support = {T32 HL066987/HL/NHLBI NIH HHS/United States ; K01 DK111790/DK/NIDDK NIH HHS/United States ; P01 CA163222/CA/NCI NIH HHS/United States ; U01 HL100001/HL/NHLBI NIH HHS/United States ; P01 HL032262/HL/NHLBI NIH HHS/United States ; T32 HL116324/HL/NHLBI NIH HHS/United States ; T32 CA009172/CA/NCI NIH HHS/United States ; R24 RR017441/RR/NCRR NIH HHS/United States ; R01 HL048801/HL/NHLBI NIH HHS/United States ; R01 AR043369/AR/NIAMS NIH HHS/United States ; U54 DK110805/DK/NIDDK NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R24 DK092760/DK/NIDDK NIH HHS/United States ; R01 DK053298/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Aquatic Organisms/classification ; *Biological Evolution ; Cytoprotection/radiation effects ; DNA Damage/radiation effects ; Hematopoietic Stem Cells/*cytology/*radiation effects ; Kidney ; Melanocytes/*cytology/*radiation effects ; Mutation ; Petromyzon/classification ; Phylogeny ; Pyrimidine Dimers/radiation effects ; Stem Cell Niche/physiology/*radiation effects ; Ultraviolet Rays/*adverse effects ; Zebrafish/classification/genetics ; }, abstract = {Haematopoietic stem and progenitor cells (HSPCs) require a specific microenvironment, the haematopoietic niche, which regulates HSPC behaviour1,2. The location of this niche varies across species, but the evolutionary pressures that drive HSPCs to different microenvironments remain unknown. The niche is located in the bone marrow in adult mammals, whereas it is found in other locations in non-mammalian vertebrates, for example, in the kidney marrow in teleost fish. Here we show that a melanocyte umbrella above the kidney marrow protects HSPCs against ultraviolet light in zebrafish. Because mutants that lack melanocytes have normal steady-state haematopoiesis under standard laboratory conditions, we hypothesized that melanocytes above the stem cell niche protect HSPCs against ultraviolet-light-induced DNA damage. Indeed, after ultraviolet-light irradiation, unpigmented larvae show higher levels of DNA damage in HSPCs, as indicated by staining of cyclobutane pyrimidine dimers and have reduced numbers of HSPCs, as shown by cmyb (also known as myb) expression. The umbrella of melanocytes associated with the haematopoietic niche is highly evolutionarily conserved in aquatic animals, including the sea lamprey, a basal vertebrate. During the transition from an aquatic to a terrestrial environment, HSPCs relocated into the bone marrow, which is protected from ultraviolet light by the cortical bone around the marrow. Our studies reveal that melanocytes above the haematopoietic niche protect HSPCs from ultraviolet-light-induced DNA damage in aquatic vertebrates and suggest that during the transition to terrestrial life, ultraviolet light was an evolutionary pressure affecting the location of the haematopoietic niche.}, } @article {pmid29899447, year = {2018}, author = {Kalia, R and Wang, RY and Yusuf, A and Thomas, PV and Agard, DA and Shaw, JM and Frost, A}, title = {Structural basis of mitochondrial receptor binding and constriction by DRP1.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {401-405}, pmid = {29899447}, issn = {1476-4687}, support = {R01 GM084970/GM/NIGMS NIH HHS/United States ; S10 OD021741/OD/NIH HHS/United States ; T32 GM008284/GM/NIGMS NIH HHS/United States ; R01 GM053466/GM/NIGMS NIH HHS/United States ; S10 OD020054/OD/NIH HHS/United States ; S10 OD021596/OD/NIH HHS/United States ; DP2 GM110772/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Allosteric Regulation ; Binding Sites/genetics ; Cryoelectron Microscopy ; Death-Associated Protein Kinases/chemistry/genetics/*metabolism/*ultrastructure ; GTP Phosphohydrolases/chemistry/genetics/metabolism/ultrastructure ; Guanosine Triphosphate/metabolism ; Humans ; Hydrolysis ; Mitochondrial Proteins/chemistry/*metabolism/*ultrastructure ; Models, Molecular ; Mutation ; Peptide Elongation Factors/chemistry/*metabolism/*ultrastructure ; Phosphorylation ; Protein Domains ; Rotation ; Structure-Activity Relationship ; }, abstract = {Mitochondrial inheritance, genome maintenance and metabolic adaptation depend on organelle fission by dynamin-related protein 1 (DRP1) and its mitochondrial receptors. DRP1 receptors include the paralogues mitochondrial dynamics proteins of 49 and 51 kDa (MID49 and MID51) and mitochondrial fission factor (MFF); however, the mechanisms by which these proteins recruit and regulate DRP1 are unknown. Here we present a cryo-electron microscopy structure of full-length human DRP1 co-assembled with MID49 and an analysis of structure- and disease-based mutations. We report that GTP induces a marked elongation and rotation of the GTPase domain, bundle-signalling element and connecting hinge loops of DRP1. In this conformation, a network of multivalent interactions promotes the polymerization of a linear DRP1 filament with MID49 or MID51. After co-assembly, GTP hydrolysis and exchange lead to MID receptor dissociation, filament shortening and curling of DRP1 oligomers into constricted and closed rings. Together, these views of full-length, receptor- and nucleotide-bound conformations reveal how DRP1 performs mechanical work through nucleotide-driven allostery.}, } @article {pmid29899446, year = {2018}, author = {Chihara, N and Madi, A and Kondo, T and Zhang, H and Acharya, N and Singer, M and Nyman, J and Marjanovic, ND and Kowalczyk, MS and Wang, C and Kurtulus, S and Law, T and Etminan, Y and Nevin, J and Buckley, CD and Burkett, PR and Buenrostro, JD and Rozenblatt-Rosen, O and Anderson, AC and Regev, A and Kuchroo, VK}, title = {Induction and transcriptional regulation of the co-inhibitory gene module in T cells.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {454-459}, pmid = {29899446}, issn = {1476-4687}, support = {P01 AI056299/AI/NIAID NIH HHS/United States ; R01 NS045937/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 CA187975/CA/NCI NIH HHS/United States ; P01 AI039671/AI/NIAID NIH HHS/United States ; P01 AI073748/AI/NIAID NIH HHS/United States ; K08 AI123516/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/*cytology/immunology/*metabolism ; CD8-Positive T-Lymphocytes/*cytology/immunology/*metabolism ; Female ; Gene Regulatory Networks/*genetics ; Immune Tolerance/genetics/immunology ; Interleukin-27/immunology ; Lymphocytes, Tumor-Infiltrating/cytology/immunology/metabolism ; Male ; Melanoma/genetics/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Positive Regulatory Domain I-Binding Factor 1/metabolism ; Proto-Oncogene Proteins c-maf/metabolism ; Receptors, Cell Surface/genetics/metabolism ; Reproducibility of Results ; *Transcription, Genetic ; }, abstract = {The expression of co-inhibitory receptors, such as CTLA-4 and PD-1, on effector T cells is a key mechanism for ensuring immune homeostasis. Dysregulated expression of co-inhibitory receptors on CD4+ T cells promotes autoimmunity, whereas sustained overexpression on CD8+ T cells promotes T cell dysfunction or exhaustion, leading to impaired ability to clear chronic viral infections and diseases such as cancer1,2. Here, using RNA and protein expression profiling at single-cell resolution in mouse cells, we identify a module of co-inhibitory receptors that includes not only several known co-inhibitory receptors (PD-1, TIM-3, LAG-3 and TIGIT) but also many new surface receptors. We functionally validated two new co-inhibitory receptors, activated protein C receptor (PROCR) and podoplanin (PDPN). The module of co-inhibitory receptors is co-expressed in both CD4+ and CD8+ T cells and is part of a larger co-inhibitory gene program that is shared by non-responsive T cells in several physiological contexts and is driven by the immunoregulatory cytokine IL-27. Computational analysis identified the transcription factors PRDM1 and c-MAF as cooperative regulators of the co-inhibitory module, and this was validated experimentally. This molecular circuit underlies the co-expression of co-inhibitory receptors in T cells and identifies regulators of T cell function with the potential to control autoimmunity and tumour immunity.}, } @article {pmid29899445, year = {2018}, author = {Chen, MC and Tippana, R and Demeshkina, NA and Murat, P and Balasubramanian, S and Myong, S and Ferré-D'Amaré, AR}, title = {Structural basis of G-quadruplex unfolding by the DEAH/RHA helicase DHX36.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {465-469}, pmid = {29899445}, issn = {1476-4687}, support = {Z99 HL999999/NULL/Intramural NIH HHS/United States ; ZIA HL006102-01/NULL/Intramural NIH HHS/United States ; DP2 GM105453/GM/NIGMS NIH HHS/United States ; GM105453/NH/NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Motifs ; Animals ; Cattle ; Crystallography, X-Ray ; DEAD-box RNA Helicases/*chemistry/genetics/*metabolism ; DNA/*chemistry/*metabolism ; Fluorescence Resonance Energy Transfer ; *G-Quadruplexes ; Models, Molecular ; Mutation ; *Nucleic Acid Denaturation ; }, abstract = {Guanine-rich nucleic acid sequences challenge the replication, transcription, and translation machinery by spontaneously folding into G-quadruplexes, the unfolding of which requires forces greater than most polymerases can exert1,2. Eukaryotic cells contain numerous helicases that can unfold G-quadruplexes 3 . The molecular basis of the recognition and unfolding of G-quadruplexes by helicases remains poorly understood. DHX36 (also known as RHAU and G4R1), a member of the DEAH/RHA family of helicases, binds both DNA and RNA G-quadruplexes with extremely high affinity4-6, is consistently found bound to G-quadruplexes in cells7,8, and is a major source of G-quadruplex unfolding activity in HeLa cell lysates 6 . DHX36 is a multi-functional helicase that has been implicated in G-quadruplex-mediated transcriptional and post-transcriptional regulation, and is essential for heart development, haematopoiesis, and embryogenesis in mice9-12. Here we report the co-crystal structure of bovine DHX36 bound to a DNA with a G-quadruplex and a 3' single-stranded DNA segment. We show that the N-terminal DHX36-specific motif folds into a DNA-binding-induced α-helix that, together with the OB-fold-like subdomain, selectively binds parallel G-quadruplexes. Comparison with unliganded and ATP-analogue-bound DHX36 structures, together with single-molecule fluorescence resonance energy transfer (FRET) analysis, suggests that G-quadruplex binding alone induces rearrangements of the helicase core; by pulling on the single-stranded DNA tail, these rearrangements drive G-quadruplex unfolding one residue at a time.}, } @article {pmid29899444, year = {2018}, author = {Crits-Christoph, A and Diamond, S and Butterfield, CN and Thomas, BC and Banfield, JF}, title = {Novel soil bacteria possess diverse genes for secondary metabolite biosynthesis.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {440-444}, doi = {10.1038/s41586-018-0207-y}, pmid = {29899444}, issn = {1476-4687}, mesh = {Acidobacteria/genetics/isolation & purification ; Bacteria/*genetics/*isolation & purification ; Biosynthetic Pathways/*genetics ; Multigene Family/genetics ; Secondary Metabolism/*genetics ; *Soil Microbiology ; }, abstract = {In soil ecosystems, microorganisms produce diverse secondary metabolites such as antibiotics, antifungals and siderophores that mediate communication, competition and interactions with other organisms and the environment1,2. Most known antibiotics are derived from a few culturable microbial taxa 3 , and the biosynthetic potential of the vast majority of bacteria in soil has rarely been investigated 4 . Here we reconstruct hundreds of near-complete genomes from grassland soil metagenomes and identify microorganisms from previously understudied phyla that encode diverse polyketide and nonribosomal peptide biosynthetic gene clusters that are divergent from well-studied clusters. These biosynthetic loci are encoded by newly identified members of the Acidobacteria, Verrucomicobia and Gemmatimonadetes, and the candidate phylum Rokubacteria. Bacteria from these groups are highly abundant in soils5-7, but have not previously been genomically linked to secondary metabolite production with confidence. In particular, large numbers of biosynthetic genes were characterized in newly identified members of the Acidobacteria, which is the most abundant bacterial phylum across soil biomes 5 . We identify two acidobacterial genomes from divergent lineages, each of which encodes an unusually large repertoire of biosynthetic genes with up to fifteen large polyketide and nonribosomal peptide biosynthetic loci per genome. To track gene expression of genes encoding polyketide synthases and nonribosomal peptide synthetases in the soil ecosystem that we studied, we sampled 120 time points in a microcosm manipulation experiment and, using metatranscriptomics, found that gene clusters were differentially co-expressed in response to environmental perturbations. Transcriptional co-expression networks for specific organisms associated biosynthetic genes with two-component systems, transcriptional activation, putative antimicrobial resistance and iron regulation, linking metabolite biosynthesis to processes of environmental sensing and ecological competition. We conclude that the biosynthetic potential of abundant and phylogenetically diverse soil microorganisms has previously been underestimated. These organisms may represent a source of natural products that can address needs for new antibiotics and other pharmaceutical compounds.}, } @article {pmid29899443, year = {2018}, author = {Hunkeler, M and Hagmann, A and Stuttfeld, E and Chami, M and Guri, Y and Stahlberg, H and Maier, T}, title = {Structural basis for regulation of human acetyl-CoA carboxylase.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {470-474}, doi = {10.1038/s41586-018-0201-4}, pmid = {29899443}, issn = {1476-4687}, mesh = {Acetyl-CoA Carboxylase/*chemistry/metabolism/*ultrastructure ; Animals ; BRCA1 Protein/chemistry/pharmacology ; Biopolymers/chemistry/metabolism ; Cell Line ; Citric Acid/pharmacology ; *Cryoelectron Microscopy ; Humans ; Models, Molecular ; Polymerization/drug effects ; Protein Domains/drug effects ; Protein Structure, Quaternary/drug effects ; Spodoptera ; Structure-Activity Relationship ; }, abstract = {Acetyl-CoA carboxylase catalyses the ATP-dependent carboxylation of acetyl-CoA, a rate-limiting step in fatty acid biosynthesis1,2. Eukaryotic acetyl-CoA carboxylases are large, homodimeric multienzymes. Human acetyl-CoA carboxylase occurs in two isoforms: the metabolic, cytosolic ACC1, and ACC2, which is anchored to the outer mitochondrial membrane and controls fatty acid β-oxidation1,3. ACC1 is regulated by a complex interplay of phosphorylation, binding of allosteric regulators and protein-protein interactions, which is further linked to filament formation1,4-8. These filaments were discovered in vitro and in vivo 50 years ago7,9,10, but the structural basis of ACC1 polymerization and regulation remains unknown. Here, we identify distinct activated and inhibited ACC1 filament forms. We obtained cryo-electron microscopy structures of an activated filament that is allosterically induced by citrate (ACC-citrate), and an inactivated filament form that results from binding of the BRCT domains of the breast cancer type 1 susceptibility protein (BRCA1). While non-polymeric ACC1 is highly dynamic, filament formation locks ACC1 into different catalytically competent or incompetent conformational states. This unique mechanism of enzyme regulation via large-scale conformational changes observed in ACC1 has potential uses in engineering of switchable biosynthetic systems. Dissecting the regulation of acetyl-CoA carboxylase opens new paths towards counteracting upregulation of fatty acid biosynthesis in disease.}, } @article {pmid29899442, year = {2018}, author = {Hublin, JJ and Ben-Ncer, A and Bailey, SE and Freidline, SE and Neubauer, S and Skinner, MM and Bergmann, I and Le Cabec, A and Benazzi, S and Harvati, K and Gunz, P}, title = {Author Correction: New fossils from Jebel Irhoud, Morocco and the pan-African origin of Homo sapiens.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {E6}, doi = {10.1038/s41586-018-0166-3}, pmid = {29899442}, issn = {1476-4687}, abstract = {In the originally published version of this Letter, the x axis in Fig. 3a should have been: 'PC1: 26%' rather than 'PC1: 46%', and the y axis should have been: 'PC2: 16%' rather than 'PC2: 29%'. We also noticed an error in the numbering of the fossils from Qafzeh: Qafzeh 27 should be removed, and Qafzeh 26 is actually Qafzeh 25, following Tillier (2014)1 and Schuh et al. (2017)2 and personal communication with B. Vandermeersch and M. D. Garralda. The correct enumeration of Qafzeh samples in the 'Mandibular metric data' section of the Methods is therefore: 'Qafzeh (9, 25)' rather than 'Qafzeh (9, 26, 27)'. Owing to the removal of Qafzeh 27, the convex hull of early modern humans changes slightly in Extended Data Fig. 1c. The sample sizes in Extended Data Fig. 1c should have read: Middle Pleistocene archaic Homo n = 19 (instead of 11), Neanderthals n = 40 (instead of 41), early modern humans n = 12 (instead of 7), and recent modern humans n = 46 (instead of 48). In Extended Data Table 2, the mean and standard deviation of corpus height and breadth at mental foramen for early modern humans should have been: x̅ = 33.15, σ = 3.26 for height (rather than x̅ = 34.23, σ = 4.57); and x̅ = 16.25, σ = 1.28 for breadth (rather than x̅ = 16.04, σ = 1.75). Accordingly, n = 12 (rather than n = 13) for both breadth and height. These errors have been corrected in the Letter online (the original Extended Data Fig. 1 is shown in Supplementary Information to this Amendment). These changes do not alter any inferences drawn from the data.}, } @article {pmid29899441, year = {2018}, author = {Simeonov, DR and Gowen, BG and Boontanrart, M and Roth, TL and Gagnon, JD and Mumbach, MR and Satpathy, AT and Lee, Y and Bray, NL and Chan, AY and Lituiev, DS and Nguyen, ML and Gate, RE and Subramaniam, M and Li, Z and Woo, JM and Mitros, T and Ray, GJ and Curie, GL and Naddaf, N and Chu, JS and Ma, H and Boyer, E and Van Gool, F and Huang, H and Liu, R and Tobin, VR and Schumann, K and Daly, MJ and Farh, KK and Ansel, KM and Ye, CJ and Greenleaf, WJ and Anderson, MS and Bluestone, JA and Chang, HY and Corn, JE and Marson, A}, title = {Author Correction: Discovery of stimulation-responsive immune enhancers with CRISPR activation.}, journal = {Nature}, volume = {559}, number = {7715}, pages = {E13}, doi = {10.1038/s41586-018-0227-7}, pmid = {29899441}, issn = {1476-4687}, support = {T32 GM067547/GM/NIGMS NIH HHS/United States ; }, abstract = {In this Letter, analysis of steady-state regulatory T (Treg) cell percentages from Il2ra enhancer deletion (EDEL) and wild-type (WT) mice revealed no differences between them (Extended Data Fig. 9d). This analysis included two mice whose genotypes were incorrectly assigned. Even after correction of the genotypes, no significant differences in Treg cell percentages were seen when data across experimental cohorts were averaged (as was done in Extended Data Fig. 9d). However, if we normalize the corrected data to account for variation among experimental cohorts, a subtle decrease in EDEL Treg cell percentages is revealed and, using the corrected and normalized data, we have redrawn Extended Data Fig. 9d in Supplementary Fig. 1. The Supplementary Information to this Amendment contains the corrected and reanalysed Extended Data Fig. 9d. The sentence "This enhancer deletion (EDEL) strain also had no obvious T cell phenotypes at steady state (Extended Data Fig. 9)." should read: "This enhancer deletion (EDEL) strain had a small decrease in the percentage of Treg cells (Extended Data Fig. 9).". This error does not affect any of the main figures in the Letter or the data from mice with the human autoimmune-associated single nucleotide polymorphism (SNP) knocked in or with a 12-base-pair deletion at the site (12DEL). In addition, we stated in the Methods that we observed consistent immunophenotypes of EDEL mice across three founders, but in fact, we observed consistent phenotypes in mice from two founders. This does not change any of our conclusions and the original Letter has not been corrected.}, } @article {pmid29899154, year = {2018}, author = {Knight, S and Lavan, N and Kanber, E and McGettigan, C}, title = {The social code of speech prosody must be specific and generalizable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6103}, pmid = {29899154}, issn = {1091-6490}, mesh = {Emotions ; *Speech ; *Speech Perception ; }, } @article {pmid29899153, year = {2018}, author = {Ponsot, E and Burred, JJ and Belin, P and Aucouturier, JJ}, title = {Reply to Knight et al.: The complexity of inferences from speech prosody should be addressed using data-driven approaches.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6104-E6105}, pmid = {29899153}, issn = {1091-6490}, mesh = {*Speech ; *Speech Perception ; }, } @article {pmid29899152, year = {2018}, author = {Pincheira-Donoso, D and Hodgson, DJ}, title = {No evidence that extinction risk increases in the largest and smallest vertebrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5845-E5846}, pmid = {29899152}, issn = {1091-6490}, mesh = {Animals ; *Extinction, Biological ; *Vertebrates ; }, } @article {pmid29899151, year = {2018}, author = {Ripple, WJ and Wolf, C and Newsome, TM and Hoffmann, M and Wirsing, AJ and McCauley, DJ}, title = {Reply to Pincheira-Donoso and Hodgson: Both the largest and smallest vertebrates have elevated extinction risk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5847-E5848}, pmid = {29899151}, issn = {1091-6490}, mesh = {Animals ; *Extinction, Biological ; Risk ; *Vertebrates ; }, } @article {pmid29899150, year = {2018}, author = {Xu, RG and Leng, Y}, title = {Squeezing and stick-slip friction behaviors of lubricants in boundary lubrication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6560-6565}, pmid = {29899150}, issn = {1091-6490}, abstract = {The fundamental questions of how lubricant molecules organize into a layered structure under nanometers confinement and what is the interplay between layering and friction are still not well answered in the field of nanotribology. While the phase transition of lubricants during a squeeze-out process under compression is a long-standing controversial debate (i.e., liquid-like to solid-like phase transition versus amorphous glass-like transition), recent different interpretations to the stick-slip friction of lubricants in boundary lubrication present new challenges in this field. We carry out molecular dynamics simulations of a model lubricant film (cyclohexane) confined between molecularly smooth surfaces (mica)--a prototypical model system studied in surface force apparatus or surface force balance experiments. Through fully atomistic simulations, we find that repulsive force between two solid surfaces starts at about seven lubricant layers (n = 7) and the lubricant film undergoes a sudden liquid-like to solid-like phase transition at n < 6 monolayers thickness. Shear of solidified lubricant films at three- or four-monolayer thickness results in stick-slip friction. The sliding friction simulation shows that instead of shear melting of the film during the slip of the surface, boundary slips at solid-lubricant interfaces happen, while the solidified structure of the lubricant film is well maintained during repeated stick-slip friction cycles. Moreover, no dilation of the lubricant film during the slip is observed, which is surprisingly consistent with recent surface force balance experimental measurements.}, } @article {pmid29899149, year = {2018}, author = {Kulesa, A and Kehe, J and Hurtado, JE and Tawde, P and Blainey, PC}, title = {Combinatorial drug discovery in nanoliter droplets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6685-6690}, pmid = {29899149}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/pharmacology ; *Combinatorial Chemistry Techniques ; Drug Discovery/*methods ; Drug Evaluation, Preclinical/*methods ; Drug Synergism ; Erythromycin/pharmacology ; Escherichia coli/drug effects ; *High-Throughput Screening Assays ; *Lab-On-A-Chip Devices ; Microarray Analysis ; Microbial Sensitivity Tests ; Nanotechnology ; Novobiocin/pharmacology ; Pseudomonas aeruginosa/drug effects ; Small Molecule Libraries/pharmacology ; Vancomycin/pharmacology ; }, abstract = {Combinatorial drug treatment strategies perturb biological networks synergistically to achieve therapeutic effects and represent major opportunities to develop advanced treatments across a variety of human disease areas. However, the discovery of new combinatorial treatments is challenged by the sheer scale of combinatorial chemical space. Here, we report a high-throughput system for nanoliter-scale phenotypic screening that formulates a chemical library in nanoliter droplet emulsions and automates the construction of chemical combinations en masse using parallel droplet processing. We applied this system to predict synergy between more than 4,000 investigational and approved drugs and a panel of 10 antibiotics against Escherichia coli, a model gram-negative pathogen. We found a range of drugs not previously indicated for infectious disease that synergize with antibiotics. Our validated hits include drugs that synergize with the antibiotics vancomycin, erythromycin, and novobiocin, which are used against gram-positive bacteria but are not effective by themselves to resolve gram-negative infections.}, } @article {pmid29899148, year = {2018}, author = {Abbas, M and Hernández-García, J and Pollmann, S and Samodelov, SL and Kolb, M and Friml, J and Hammes, UZ and Zurbriggen, MD and Blázquez, MA and Alabadí, D}, title = {Auxin methylation is required for differential growth in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6864-6869}, pmid = {29899148}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins/*biosynthesis/genetics/*metabolism ; Gene Expression Regulation, Plant/*physiology ; Hypocotyl/genetics/*growth & development ; Indoleacetic Acids/*metabolism ; Methylation ; Methyltransferases/genetics/*metabolism ; Mutation ; }, abstract = {Asymmetric auxin distribution is instrumental for the differential growth that causes organ bending on tropic stimuli and curvatures during plant development. Local differences in auxin concentrations are achieved mainly by polarized cellular distribution of PIN auxin transporters, but whether other mechanisms involving auxin homeostasis are also relevant for the formation of auxin gradients is not clear. Here we show that auxin methylation is required for asymmetric auxin distribution across the hypocotyl, particularly during its response to gravity. We found that loss-of-function mutants in Arabidopsis IAA CARBOXYL METHYLTRANSFERASE1 (IAMT1) prematurely unfold the apical hook, and that their hypocotyls are impaired in gravitropic reorientation. This defect is linked to an auxin-dependent increase in PIN gene expression, leading to an increased polar auxin transport and lack of asymmetric distribution of PIN3 in the iamt1 mutant. Gravitropic reorientation in the iamt1 mutant could be restored with either endodermis-specific expression of IAMT1 or partial inhibition of polar auxin transport, which also results in normal PIN gene expression levels. We propose that IAA methylation is necessary in gravity-sensing cells to restrict polar auxin transport within the range of auxin levels that allow for differential responses.}, } @article {pmid29899147, year = {2018}, author = {Bleichert, F and Leitner, A and Aebersold, R and Botchan, MR and Berger, JM}, title = {Conformational control and DNA-binding mechanism of the metazoan origin recognition complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5906-E5915}, pmid = {29899147}, issn = {1091-6490}, support = {670821//European Research Council/International ; R01 CA030490/CA/NCI NIH HHS/United States ; S10 OD012342/OD/NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle Proteins/chemistry/metabolism ; DNA/*chemistry/metabolism ; Drosophila Proteins/chemistry/metabolism ; Drosophila melanogaster ; Humans ; Minichromosome Maintenance Proteins/*chemistry/metabolism ; Nuclear Proteins/chemistry/metabolism ; Origin Recognition Complex/*chemistry/metabolism ; }, abstract = {In eukaryotes, the heterohexameric origin recognition complex (ORC) coordinates replication onset by facilitating the recruitment and loading of the minichromosome maintenance 2-7 (Mcm2-7) replicative helicase onto DNA to license origins. Drosophila ORC can adopt an autoinhibited configuration that is predicted to prevent Mcm2-7 loading; how the complex is activated and whether other ORC homologs can assume this state are not known. Using chemical cross-linking and mass spectrometry, biochemical assays, and electron microscopy (EM), we show that the autoinhibited state of Drosophila ORC is populated in solution, and that human ORC can also adopt this form. ATP binding to ORC supports a transition from the autoinhibited state to an active configuration, enabling the nucleotide-dependent association of ORC with both DNA and Cdc6. An unstructured N-terminal region adjacent to the conserved ATPase domain of Orc1 is shown to be required for high-affinity ORC-DNA interactions, but not for activation. ORC optimally binds DNA duplexes longer than the predicted footprint of the ORC ATPases associated with a variety of cellular activities (AAA+) and winged-helix (WH) folds; cryo-EM analysis of Drosophila ORC bound to DNA and Cdc6 indicates that ORC contacts DNA outside of its central core region, bending the DNA away from its central DNA-binding channel. Our findings indicate that ORC autoinhibition may be common to metazoans and that ORC-Cdc6 remodels origin DNA before Mcm2-7 recruitment and loading.}, } @article {pmid29899146, year = {2018}, author = {Prieve, DC and Malone, SM and Khair, AS and Stout, RF and Kanj, MY}, title = {Diffusiophoresis of charged colloidal particles in the limit of very high salinity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1701391115}, pmid = {29899146}, issn = {1091-6490}, abstract = {Diffusiophoresis is the migration of a colloidal particle through a viscous fluid, caused by a gradient in concentration of some molecular solute; a long-range physical interaction between the particle and solute molecules is required. In the case of a charged particle and an ionic solute (e.g., table salt, NaCl), previous studies have predicted and experimentally verified the speed for very low salt concentrations at which the salt solution behaves ideally. The current study presents a study of diffusiophoresis at much higher salt concentrations (approaching the solubility limit). At such large salt concentrations, electrostatic interactions are almost completely screened, thus eliminating the long-range interaction required for diffusiophoresis; moreover, the high volume fraction occupied by ions makes the solution highly nonideal. Diffusiophoretic speeds were found to be measurable, albeit much smaller than for the same gradient at low salt concentrations.}, } @article {pmid29899145, year = {2018}, author = {Lou, K and Granick, S and Amblard, F}, title = {How to better focus waves by considering symmetry and information loss.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6554-6559}, pmid = {29899145}, issn = {1091-6490}, abstract = {We amend the general belief that waves with extended spherical wavefront focus at their center of curvature. Instead, when the spherical symmetry of waves is broken by propagating them through a finite aperture along an average direction, the forward/backward symmetry is broken and the focal volume shifts its center backward along that direction. The extent of this focal shift increases as smaller apertures are used, up to the point that the nominal focal plane is out of focus. Furthermore, the loss of axial symmetry with noncircular apertures causes distinct focal shifts in distinct axial planes, and the resulting astigmatism possibly degrades the axial focusing resolution. Using experiments and simulations, focal shift with noncircular apertures is described for classical and temporal focusing. The usefulness of these conclusions to improve imaging resolution is demonstrated in a high-resolution optical microscopy application, namely line-temporal focusing microscopy. These conclusions follow from fundamental symmetries of the wave geometry and matter for an increasing number of emerging optical techniques. This work offers a general framework and strategy to understand and improve virtually any wave-based application whose efficacy depends on optimal focusing and may be helpful when information is transmitted by waves in applications from electromagnetic communications, to biological and astronomical imaging, to lithography and even warfare.}, } @article {pmid29899144, year = {2018}, author = {Kristensen, KK and Midtgaard, SR and Mysling, S and Kovrov, O and Hansen, LB and Skar-Gislinge, N and Beigneux, AP and Kragelund, BB and Olivecrona, G and Young, SG and Jørgensen, TJD and Fong, LG and Ploug, M}, title = {A disordered acidic domain in GPIHBP1 harboring a sulfated tyrosine regulates lipoprotein lipase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6020-E6029}, pmid = {29899144}, issn = {1091-6490}, support = {P01 HL090553/HL/NHLBI NIH HHS/United States ; R01 HL087228/HL/NHLBI NIH HHS/United States ; R01 HL125335/HL/NHLBI NIH HHS/United States ; }, mesh = {Angiopoietin-like 4 Protein/chemistry/genetics/metabolism ; Animals ; Endothelial Cells/*metabolism/pathology ; Humans ; Hyperlipoproteinemia Type I/genetics/metabolism/pathology ; Lipoprotein Lipase/chemistry/genetics/*metabolism ; Mice ; Protein Binding ; Protein Domains ; Receptors, Lipoprotein/chemistry/genetics/*metabolism ; Tyrosine/chemistry/genetics/metabolism ; }, abstract = {The intravascular processing of triglyceride-rich lipoproteins depends on lipoprotein lipase (LPL) and GPIHBP1, a membrane protein of endothelial cells that binds LPL within the subendothelial spaces and shuttles it to the capillary lumen. In the absence of GPIHBP1, LPL remains mislocalized within the subendothelial spaces, causing severe hypertriglyceridemia (chylomicronemia). The N-terminal domain of GPIHBP1, an intrinsically disordered region (IDR) rich in acidic residues, is important for stabilizing LPL's catalytic domain against spontaneous and ANGPTL4-catalyzed unfolding. Here, we define several important properties of GPIHBP1's IDR. First, a conserved tyrosine in the middle of the IDR is posttranslationally modified by O-sulfation; this modification increases both the affinity of GPIHBP1-LPL interactions and the ability of GPIHBP1 to protect LPL against ANGPTL4-catalyzed unfolding. Second, the acidic IDR of GPIHBP1 increases the probability of a GPIHBP1-LPL encounter via electrostatic steering, increasing the association rate constant (kon) for LPL binding by >250-fold. Third, we show that LPL accumulates near capillary endothelial cells even in the absence of GPIHBP1. In wild-type mice, we expect that the accumulation of LPL in close proximity to capillaries would increase interactions with GPIHBP1. Fourth, we found that GPIHBP1's IDR is not a key factor in the pathogenicity of chylomicronemia in patients with the GPIHBP1 autoimmune syndrome. Finally, based on biophysical studies, we propose that the negatively charged IDR of GPIHBP1 traverses a vast space, facilitating capture of LPL by capillary endothelial cells and simultaneously contributing to GPIHBP1's ability to preserve LPL structure and activity.}, } @article {pmid29898790, year = {2018}, author = {Fujita, T and Yuno, M and Fujii, H}, title = {An enChIP system for the analysis of bacterial genome functions.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {387}, pmid = {29898790}, issn = {1756-0500}, support = {15K06895//Ministry of Education, Culture, Sports, Science and Technology/ ; 15H04329//Ministry of Education, Culture, Sports, Science and Technology/ ; 15H04329//Ministry of Education, Culture, Sports, Science and Technology/ ; 15H01354//Ministry of Education, Culture, Sports, Science and Technology/ ; }, mesh = {Chromatin Immunoprecipitation/*methods ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; DNA, Bacterial/*genetics ; Escherichia coli/*genetics ; Genome, Bacterial/*genetics ; Plasmids ; }, abstract = {OBJECTIVE: The engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology enables purification of specific genomic regions interacting with their associated molecules. In enChIP, the locus to be purified is first tagged with engineered DNA-binding molecules. An example of such engineered DNA-binding molecules to tag the locus of interest is the clustered regularly interspaced short palindromic repeats (CRISPR) system, consisting of a catalytically-inactive form of Cas9 (dCas9) and guide RNA (gRNA). Subsequently, the tagged locus is subjected to affinity purification for identification of interacting molecules. In our previous studies, we developed enChIP systems for analysis of mammalian genome functions. Here, we developed an enChIP system to analyze bacterial genome functions.

RESULTS: We generated a plasmid inducibly expressing Streptococcus pyogenes dCas9 fused to a 3xFLAG-tag (3xFLAG-dCas9) in bacteria. Inducible expression of 3xFLAG-dCas9 in Escherichia coli was confirmed by immunoblot analysis. We were able to purify specific genomic regions of E. coli preserving their molecular interactions. The system is potentially useful for analysis of interactions between specific genomic regions and their associated molecules in bacterial cells to understand genome functions such as transcription, DNA repair, and DNA recombination.}, } @article {pmid29898783, year = {2018}, author = {Ioannou, M and Papageorgiou, DN and Ogryzko, V and Strouboulis, J}, title = {Mammalian expression vectors for metabolic biotinylation tandem affinity tagging by co-expression in cis of a mammalian codon-optimized BirA biotin ligase.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {390}, pmid = {29898783}, issn = {1756-0500}, support = {R01 DK083389/DK/NIDDK NIH HHS/United States ; RO1DK083389//National Institute of Diabetes and Digestive and Kidney Diseases/ ; }, mesh = {*Affinity Labels ; Animals ; Biotinylation/*methods ; *Genetic Vectors ; HEK293 Cells ; Humans ; Mice ; Plasmids ; Rabbits ; Rats ; }, abstract = {ΟBJECTIVE: To construct mammalian expression vectors for the N- or C-terminal tagging of proteins with a tandem affinity tag comprised of the biotinylatable Avi tag and of a triple FLAG tag.

RESULTS: We constructed and tested by transient transfections mammalian expression vectors for the co-expression from a single plasmid of N- or C-terminally tagged proteins bearing a tandem affinity tag comprised of the biotinylatable Avi tag and of a triple FLAG tag separated by a tobacco etch virus (TEV) protease cleavage site, together with a mammalian codon-optimized BirA biotin ligase fused to green fluorescent protein. We also describe platform vectors for the N- or C-terminal AVI-TEV-FLAG tagging of any complementary DNA of choice. These vectors offer versatility and efficiency in the application of metabolic biotinylation tandem affinity tagging of nuclear proteins in mammalian cells.}, } @article {pmid29898778, year = {2018}, author = {Gunadi, and Gunawan, TA and Widiyanto, G and Yuanita, A and Mulyani, NS and Makhmudi, A}, title = {Liver transplant score for prediction of biliary atresia patients' survival following Kasai procedure.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {381}, pmid = {29898778}, issn = {1756-0500}, mesh = {Biliary Atresia/epidemiology/*surgery ; Female ; Humans ; Indonesia/epidemiology ; Infant ; Liver Transplantation/*statistics & numerical data ; Male ; Outcome Assessment (Health Care)/*statistics & numerical data ; Portoenterostomy, Hepatic/mortality/*statistics & numerical data ; Prognosis ; Retrospective Studies ; }, abstract = {OBJECTIVES: Recently, a scoring system has been developed to predict which patients with biliary atresia (BA) who underwent a Kasai procedure should be considered for liver transplant. Here, we applied the scoring system to predict the survival of BA patients following the Kasai procedure at Dr. Sardjito Hospital, Yogyakarta, Indonesia from January 2012 to January 2016.

RESULTS: There were 26 patients, of whom 14 were males and 12 females. Outcomes of BA patients after the Kasai surgery were 15 survived and 11 died. There were significant associations between ascites and sepsis with the liver transplant score of ≥ 8 (p value = 0.006 and 0.014, respectively), whereas post-operative bilirubin level, ALT level, prothrombin time, cirrhosis, esophageal varices, portal hypertension, and cholangitis did not significantly correlate to the score. The patients with a score ≥ 8 have a relatively greater risk by 3.5-fold to die compared with patients with a score < 8, but it did not reach a significant level (p value = 0.13). In conclusions, the incidence of ascites and sepsis might predict the poor prognosis of BA patients following the Kasai procedure. Moreover, patients with a score ≥ 8 are prone to die after the Kasai surgery if they do not undergo a liver transplant.}, } @article {pmid29898775, year = {2018}, author = {Herath, HMMTB and Keragala, BSDP and Udeshika, WAE and Samarawickrama, SSM and Pahalagamage, SP and Kulatunga, A and Rodrigo, C}, title = {Knowledge, attitudes and skills in melanoma diagnosis among doctors: a cross sectional study from Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {389}, pmid = {29898775}, issn = {1756-0500}, mesh = {Adult ; *Clinical Competence ; Cross-Sectional Studies ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; *Medical Staff, Hospital ; Melanoma/*diagnosis ; Physician-Patient Relations ; Skin Neoplasms/*diagnosis ; Sri Lanka ; }, abstract = {OBJECTIVES: This study aimed to assess the knowledge, attitudes and skills of non-specialist doctors on timely referral of suspicious lesions for melanoma diagnosis.

RESULTS: One hundred and twenty-three doctors (mean age; 30.4 years, SD ± 8.015) were enrolled. Very few (3.3%) correctly stated all four types of melanoma. Only 8.1% of the total sample had been trained to perform a total body examination for skin cancer detection and a majority (110/123) had never performed one. Almost all (95.2%) were not confident in using a dermatoscope for examination of a skin lesion. Only 17.9% of participants had discussed skin cancer/melanoma risk reduction with patients. Only 13.8% had educated at least one patient regarding skin self-examination for suspicious skin lesions. Knowledge and clinical skills regarding melanoma recognition was unsatisfactory in our sample. Urgent attention is needed to bridge the gap in knowledge and clinical skills on this topic.}, } @article {pmid29898773, year = {2018}, author = {Cantín, CM and Arús, P and Eduardo, I}, title = {Identification of a new allele of the Dw gene causing brachytic dwarfing in peach.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {386}, pmid = {29898773}, issn = {1756-0500}, mesh = {Alleles ; Gene Expression Regulation, Plant/*genetics ; Genes, Plant/*genetics ; Genetic Markers ; Mutation/genetics ; Polymorphism, Single Nucleotide/genetics ; Prunus persica/*anatomy & histology/*genetics ; Trees/*genetics ; }, abstract = {OBJECTIVE: Peach brachytic dwarfism determined by Dwarf gene (Dw) is an undesired trait segregating in some peach breeding programs. Recently, a single nucleotide polymorphism (SNP) mutation in the gibberellin insensitive dwarf 1 (GID1) peach gene causing brachytic dwarfism was described. In this research we wanted to validate this marker in an F2 population of the 'Nectavantop' peach cultivar (Nv) to include it as a marker assisted selection tool for peach breeding programs.

RESULTS: The observed segregation of the trait was in agreement with that of a recessive gene, the individuals homozygous for the recessive allele (dwdw) presenting the dwarf genotype. Dw was mapped to the distal part of linkage group 6 as previously described. The SNP marker based on the causal mutation previously described did not segregate in Nv F2 population. The sequence of the GID1c gene in Nv revealed a second SNP in its coding sequence which cosegregated with the dwarf phenotype. This SNP was predicted by the SNAP2 software to cause a major functional change and was validated in the dwarf peach cultivar 'Small sunning'. These results suggest the existence of at least two independent mutations of the Dw gene causing the peach brachytic dwarf phenotype.}, } @article {pmid29898772, year = {2018}, author = {Sillo, TO and Lloyd-Owen, S and White, E and Abolghasemi-Malekabadi, K and Lock-Pullan, P and Ali, M and Perry, A and Robinson, SJ and Wadley, MS}, title = {The impact of bariatric surgery on the resolution of obstructive sleep apnoea.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {385}, pmid = {29898772}, issn = {1756-0500}, mesh = {Adult ; Bariatric Surgery/*methods ; Female ; Gastric Bypass/methods ; Gastroplasty/methods ; Humans ; Male ; Middle Aged ; Obesity, Morbid/complications/*surgery ; *Outcome Assessment (Health Care) ; Sleep Apnea, Obstructive/etiology/*therapy ; *Weight Loss ; }, abstract = {OBJECTIVE: Obesity is associated with a high incidence of obstructive sleep apnoea (OSA). Bariatric surgery is postulated to lead to OSA resolution, but there is inconclusive evidence on its efficacy. We used objective measurements to determine the rate of resolution or improvement of OSA in patients who had bariatric procedures in our unit.

RESULTS: Data was analysed on all patients with OSA who underwent bariatric procedures [laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG)] between June 2012 and September 2016 in our unit. 47 patients (26.7%) were diagnosed with OSA. Mean age was 48.5 years. 63.8% were female. 43 required nocturnal continuous positive airway pressure (CPAP) support. Procedures were LRYGB (n = 26) and LSG (n = 21). Mean excess weight loss was 56.1%. Mean start apnoea-hypopnoea index (AHI) on CPAP was 6.4 events/hr and end AHI was 1.4 events/h. 14 patients (32.6%) had complete OSA resolution and 12 (27.9%) showed improvement in pressure support requirements. We demonstrated that 55.3% of patients had resolution or improvement in OSA following bariatric surgery. However, there was a high rate of non-attendance of follow-up appointments. Future efforts will involve analysis of the reasons for this to ensure more robust monitoring.}, } @article {pmid29898771, year = {2018}, author = {Telles, S and Pal, S and Sharma, SK and Singh, A and Kala, N and Balkrishna, A}, title = {The association between the lipid profile and fasting blood glucose with weight related outcomes in healthy obese adults.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {383}, pmid = {29898771}, issn = {1756-0500}, mesh = {Adult ; Blood Glucose/*analysis ; *Body Mass Index ; Cholesterol, HDL/*blood ; Comorbidity ; Diabetes Mellitus/*blood/epidemiology ; Female ; Humans ; India/epidemiology ; Lipoproteins/*blood ; Male ; Middle Aged ; Obesity/*blood/epidemiology ; Prediabetic State/blood/epidemiology ; Triglycerides/*blood ; *Waist Circumference ; }, abstract = {OBJECTIVES: The present study was conducted on healthy obese persons to determine: (i) the association between total cholesterol, triglycerides, HDL cholesterol, total cholesterol/HDL ratio and fasting blood glucose (FBG) with (a) BMI, (b) waist circumference (WC) and (c) body fat and (ii) the presence of undiagnosed type 2 diabetes (based on fasting blood glucose) in the participants. There were 1140 participants of both sexes (female:male 697:443; group mean age 44.0 ± 10.8 years; BMI ≥ 25 kg/m2) from four regions of India. The participants were assessed for (i) BMI and WC, (ii) body fat, (iii) fasting serum lipid profile and (iv) FBG. Statistical significance (α) was set at 0.05.

RESULTS: Based on a linear regression analysis triglycerides acted as a significant predictor for body fat. Triglycerides showed a significant negative correlation with BMI and body fat. HDL cholesterol was significantly negatively correlated with waist circumference and positively correlated with body fat. Total cholesterol/HDL ratio was positively correlated with waist circumference and negatively correlated with body fat. A significant positive correlation of FBG and waist circumference was also observed. Among the healthy participants 34.2% had pre-diabetes and 13.6% had diabetes.}, } @article {pmid29898769, year = {2018}, author = {Esemu, SN and Ndip, RN and Ndip, LM}, title = {Detection of Ehrlichia ruminantium infection in cattle in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {388}, pmid = {29898769}, issn = {1756-0500}, mesh = {Animals ; Cameroon/epidemiology ; Cattle ; Cattle Diseases/*diagnosis/epidemiology/microbiology ; Cross-Sectional Studies ; Ehrlichia ruminantium/*isolation & purification ; Female ; Heartwater Disease/*diagnosis/epidemiology/microbiology ; Male ; Polymerase Chain Reaction ; Tick Infestations/*diagnosis/epidemiology/veterinary ; }, abstract = {OBJECTIVES: Ehrlichia ruminantium infection (heartwater) is a major constraint that impacts negatively on the cattle industry development in sub-Saharan Africa and so far, little is known of the presence of heartwater in cattle in Cameroon. This study sought to investigate the prevalence of E. ruminantium infection in cattle in Cameroon and to determine the predictors of infection.

RESULTS: A species-specific semi-nested pCS20 polymerase chain reaction was used to screen the buffy coats from 182 cattle (comprising 82 cattle that received intensive tick control regimen and 100 cattle on strategic tick control) from two study sites in Cameroon for E. ruminantium DNA in a cross-sectional study. E. ruminantium infection was confirmed in 12 (6.6%) of the 182 cattle comprising 11 that received intensive tick control and one on strategic tick control. Of the 12 cattle detected, 11 were apparently healthy and one was clinically diagnosed of heartwater. All DNA sequences of pCS20 amplicons were identical to each other (a representative sequence deposited in GenBank under accession number JQ039939). These findings which have veterinary and epidemiological significance, suggest the need for further investigation to determine the extent and role of heartwater in cattle in Cameroon.}, } @article {pmid29898767, year = {2018}, author = {Ang, JS and Aloise, MN and Dawes, D and Dempster, MG and Fraser, R and Paterson, A and Stanley, P and Suarez-Gonzalez, A and Dawes, M and Katzov-Eckert, H}, title = {Evaluation of buccal swabs for pharmacogenetics.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {382}, pmid = {29898767}, issn = {1756-0500}, mesh = {Adult ; DNA Copy Number Variations ; Genotyping Techniques/*methods/standards ; Humans ; *Mouth Mucosa ; Pharmacogenetics/*methods/standards ; Polymorphism, Single Nucleotide ; Real-Time Polymerase Chain Reaction ; Specimen Handling/*methods/standards ; }, abstract = {OBJECTIVE: A simple, non-invasive sample collection method is key for the integration of pharmacogenetics into clinical practice. The aim of this study was to gain samples for pharmacogenetic testing and evaluate the variation between dry-flocked and sponge-tipped buccal swabs in yield and quality of DNA isolated.

RESULTS: Thirty-one participants collected samples using dry-flocked swabs and sponge-tipped swabs. Samples were assessed for DNA yield, quality and genotyping performance on a qPCR OpenArray platform of 28 pharmacogenetic SNPs and a CYP2D6 TaqMan copy number variant. DNA from sponge-tipped swabs had a significantly greater yield compared to DNA collected with dry-flocked swabs (p = 4.4 × 10-7). Moreover, highest genotyping call rates across all assays and highest CNV confidence scores were observed in DNA samples collected from sponge-tipped swabs (97% vs. 54% dry-flocked swabs; 0.99 vs. 0.88 dry-flocked swabs, respectively). Sample collection using sponge-tipped swabs provides a DNA source of sufficient quantity and quality for pharmacogenetic variant detection using qPCR.}, } @article {pmid29898760, year = {2018}, author = {Soko, ND and Masimirembwa, C and Dandara, C}, title = {A cost effective RFLP method to genotype Solute carrier organic anion 1B1 (SLCO1B1) c.1929A>C (p.Leu643Phe, rs34671512); a variant with potential effect on rosuvastatin pharmacokinetics.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {384}, pmid = {29898760}, issn = {1756-0500}, support = {SIR//South African Medical Research Council/ ; }, mesh = {Adolescent ; Adult ; African Continental Ancestry Group/*genetics ; Genotyping Techniques/economics/*methods ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*pharmacokinetics ; Liver-Specific Organic Anion Transporter 1/*genetics ; Male ; Pharmacogenomic Testing/economics/*methods ; Polymorphism, Restriction Fragment Length/*genetics ; Rosuvastatin Calcium/*pharmacokinetics ; Young Adult ; }, abstract = {OBJECTIVE: This study describes a restriction fragment polymorphism protocol for rapidly screening the polymorphism SLCO1B1 c.1929A>C in genomic DNA samples. The polymorphism SLCO1B1 c.1929A>C has been associated with increased activity resulting in increased hepatic uptake of drugs. Currently SLCO1B1 c.1929A>C is genotyped using direct sequencing techniques and 5' nuclease based assays which can be cost prohibiting in resource limited settings. The aim of this study therefore was to design and validate a cost effective RFLP for genotyping the SLCO1B1 c.1929A>C polymorphism. This study was designed to investigate the effect of the polymorphism SLCO1B1 c.1929A>C on interindividual variability in rosuvastatin pharmacokinetics in healthy volunteers of African descent.

RESULTS: We describe a restriction fragment length polymorphism method to genotype SLCO1B1 c.1929A>C polymorphism using the restriction enzyme Ase1. A student's t test with Welch correction was used to establish association between the SLCO1B1 c.1929A>C variant and rosuvastatin exposure. The frequency of the SLCO1B1 c.1929C allele amongst Zimbabweans was 6%. The SLCO1B1 c.1929C allele was associated with a 75% reduction (P < 0.001) in rosuvastatin exposure when compared to individuals carrying the wild type SLCO1B1 c.1929A allele. Polymorphism c.1929A>C may therefore play a significant role in rosuvastatin response. The RFLP method is quick and cost effective.}, } @article {pmid29898720, year = {2018}, author = {Li, C and Zhang, L and Nie, Q}, title = {Landscape reveals critical network structures for sharpening gene expression boundaries.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {67}, pmid = {29898720}, issn = {1752-0509}, support = {R01GM107264;R01ED023050;R01NS095355//National Institutes of Health/ ; 11421110001//National Natural Science Foundation of China/ ; 11622102//National Natural Science Foundation of China/ ; R01 GM107264/GM/NIGMS NIH HHS/United States ; 17ZR1444500//Natural Science Foundation of Shanghai (CN)/ ; R01 NS095355/NS/NINDS NIH HHS/United States ; DMS1562176//National Science Foundation/ ; 11771098//National Natural Science Foundation of China/ ; 91430217//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Spatial pattern formation is a critical issue in developmental biology. Gene expression boundary sharpening has been observed from both experiments and modeling simulations. However, the mechanism to determine the sharpness of the boundary is not fully elucidated.

RESULTS: We investigated the boundary sharpening resulted by three biological motifs, interacting with morphogens, and uncovered their probabilistic landscapes. The landscape view, along with calculated average switching time between attractors, provides a natural explanation for the boundary sharpening behavior relying on the noise induced gene state switchings. To possess boundary sharpening potential, a gene network needs to generate an asymmetric bistable state, i.e. one of the two stable states is less stable than the other. We found that the mutual repressed self-activation model displays more robust boundary sharpening ability against parameter perturbation, compared to the mutual repression or the self-activation model. This is supported by the results of switching time calculated from the landscape, which indicate that the mutual repressed self-activation model has shortest switching time, among three models. Additionally, introducing cross gradients of morphogens provides a more stable mechanism for the boundary sharpening of gene expression, due to a two-way switching mechanism.

CONCLUSIONS: Our results reveal the underlying principle for the gene expression boundary sharpening, and pave the way for the mechanistic understanding of cell fate decisions in the pattern formation processes of development.}, } @article {pmid29898718, year = {2018}, author = {Casagranda, S and Touzeau, S and Ropers, D and Gouzé, JL}, title = {Principal process analysis of biological models.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {68}, pmid = {29898718}, issn = {1752-0509}, support = {ANR-11-BINF-0005//Investissements d'Avenir Bio-informatique programme under project RESET/ ; NR-11-LABX-0028-01//Program LABEX SIGNALIFE/ ; }, abstract = {BACKGROUND: Understanding the dynamical behaviour of biological systems is challenged by their large number of components and interactions. While efforts have been made in this direction to reduce model complexity, they often prove insufficient to grasp which and when model processes play a crucial role. Answering these questions is fundamental to unravel the functioning of living organisms.

RESULTS: We design a method for dealing with model complexity, based on the analysis of dynamical models by means of Principal Process Analysis. We apply the method to a well-known model of circadian rhythms in mammals. The knowledge of the system trajectories allows us to decompose the system dynamics into processes that are active or inactive with respect to a certain threshold value. Process activities are graphically represented by Boolean and Dynamical Process Maps. We detect model processes that are always inactive, or inactive on some time interval. Eliminating these processes reduces the complex dynamics of the original model to the much simpler dynamics of the core processes, in a succession of sub-models that are easier to analyse. We quantify by means of global relative errors the extent to which the simplified models reproduce the main features of the original system dynamics and apply global sensitivity analysis to test the influence of model parameters on the errors.

CONCLUSION: The results obtained prove the robustness of the method. The analysis of the sub-model dynamics allows us to identify the source of circadian oscillations. We find that the negative feedback loop involving proteins PER, CRY, CLOCK-BMAL1 is the main oscillator, in agreement with previous modelling and experimental studies. In conclusion, Principal Process Analysis is a simple-to-use method, which constitutes an additional and useful tool for analysing the complex dynamical behaviour of biological systems.}, } @article {pmid29898669, year = {2018}, author = {Schwaha, TF and Handschuh, S and Ostrovsky, AN and Wanninger, A}, title = {Morphology of the bryozoan Cinctipora elegans (Cyclostomata, Cinctiporidae) with first data on its sexual reproduction and the cyclostome neuro-muscular system.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {92}, pmid = {29898669}, issn = {1471-2148}, support = {P22696-B17//Austrian Science Fund/International ; P27933-B29//Austrian Science Fund/International ; 16-04-00243-a//Russian Foundation for Basic Research/International ; 1.38.233.2015//Saint Petersburg State University/International ; 1.42.1099.2016//Saint Petersburg State University/International ; 1.42.739.2017//Saint Petersburg State University/International ; }, mesh = {Animal Structures/anatomy & histology/innervation ; Animals ; Bryozoa/*anatomy & histology/*physiology ; Gastrointestinal Tract/anatomy & histology ; Microscopy, Confocal ; Muscles/*anatomy & histology ; Nervous System/*anatomy & histology ; Oocytes/cytology ; Reproduction/physiology ; Serotonin/metabolism ; X-Ray Microtomography ; }, abstract = {BACKGROUND: Cyclostome bryozoans are an ancient group of marine colonial suspension-feeders comprising approximately 700 extant species. Previous morphological studies are mainly restricted to skeletal characters whereas data on soft tissues obtained by state-of-the-art methods are still lacking. In order to contribute to issues related to cyclostome ground pattern reconstruction, we analyzed the morphology of the neuromuscular system Cinctipora elegans by means of immunocytochemical staining, confocal laser scanning microscopy, histological sections and microCT imaging.

RESULTS: Polypides of C. elegans are located in elongated tubular skeletal cystids. Distally, the orifice leads into a prominent vestibulum which is lined by an epithelium that joins an almost complete perimetrical attachment organ, both containing radially arranged neurite bundles and muscles. Centrally, the prominent atrial sphincter separates the vestibulum from the atrium. The latter is enclosed by the tentacle sheath which contains few longitudinal muscle fibers and two principal neurite bundles. These emerge from the cerebral ganglion, which is located at the lophophoral base. Lateral ganglia are located next to the cerebral ganglion from which the visceral neurite bundles emerge that extend proximally towards the foregut. There are four tentacle neurite bundles that emerge from the ganglia and the circum-oral nerve ring, which encompasses the pharynx. The tentacles possess two striated longitudinal muscles. Short buccal dilatators are situated at the lophophoral base and short muscular sets are present at the abfrontal and frontal side of the tentacle base. The pharynx is myoepithelial and triradiate in cross-section. Oocytes are found inside the pharyngeal myoepithelium. The digestive tract contains dense circular musculature and few longitudinal muscles. The membranous sac contains regular, thin, circular and diagonal muscles and neurites in its epithelial lining.

CONCLUSIONS: The general structure of the neuro-muscular system is more reminiscent of the condition found in Gymnolaemata rather than Phylactolaemata, which supports a close relationship between Cyclostomata and Gymnolaemata. Several characters of C. elegans such as the lateral ganglia or loss of the cardia are probably apomorphic for this species. For the first time, oocytes that surprisingly develop in the pharyngeal wall are reported for this species.}, } @article {pmid29898666, year = {2018}, author = {Salvadori, G and Junges, R and Åmdal, HA and Chen, T and Morrison, DA and Petersen, FC}, title = {High-resolution profiles of the Streptococcus mitis CSP signaling pathway reveal core and strain-specific regulated genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {453}, pmid = {29898666}, issn = {1471-2164}, support = {248036//Norges Forskningsråd/ ; }, mesh = {Bacterial Proteins/*physiology ; *DNA Transformation Competence ; *Gene Expression Regulation, Bacterial ; Regulon ; Signal Transduction/genetics ; Species Specificity ; Streptococcus mitis/*genetics/metabolism ; Streptococcus pneumoniae/genetics ; Up-Regulation ; }, abstract = {BACKGROUND: In streptococci of the mitis group, competence for natural transformation is a transient physiological state triggered by competence stimulating peptides (CSPs). Although low transformation yields and the absence of a widespread functional competence system have been reported for Streptococcus mitis, recent studies revealed that, at least for some strains, high efficiencies can be achieved following optimization protocols. To gain a deeper insight into competence in this species, we used RNA-seq, to map the global CSP response of two transformable strains: the type strain NCTC12261T and SK321.

RESULTS: All known genes induced by ComE in Streptococcus pneumoniae, including sigX, were upregulated in the two strains. Likewise, all sets of streptococcal SigX core genes involved in extracellular DNA uptake, recombination, and fratricide were upregulated. No significant differences in the set of induced genes were observed when the type strain was grown in rich or semi-defined media. Five upregulated operons unique to S. mitis with a SigX-box in the promoter region were identified, including two specific to SK321, and one specific to NCTC12261T. Two of the strain-specific operons coded for different bacteriocins. Deletion of the unique S. mitis sigX regulated genes had no effect on transformation.

CONCLUSIONS: Overall, comparison of the global transcriptome in response to CSP shows the conservation of the ComE and SigX-core regulons in competent S. mitis isolates, as well as species and strain-specific genes. Although some S. mitis exhibit truncations in key competence genes, this study shows that in transformable strains, competence seems to depend on the same core genes previously identified in S. pneumoniae.}, } @article {pmid29898665, year = {2018}, author = {Valverde, JR and Gullón, S and Mellado, RP}, title = {Modelling the metabolism of protein secretion through the Tat route in Streptomyces lividans.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {59}, pmid = {29898665}, issn = {1471-2180}, abstract = {BACKGROUND: Streptomyces lividans has demonstrated its value as an efficient host for protein production due to its ability to secrete functional proteins directly to the media. Secretory proteins that use the major Sec route need to be properly folded outside the cell, whereas secretory proteins using the Tat route appear outside the cell correctly folded. This feature makes the Tat system very attractive for the production of natural or engineered Tat secretory proteins. S. lividans cells are known to respond differently to overproduction and secretion of Tat versus Sec proteins. Increased understanding of the impact of protein secretion through the Tat route can be obtained by a deeper analysis of the metabolic impact associated with protein production, and its dependence on protein origin, composition, secretion mechanisms, growth phases and nutrients. Flux Balance Analysis of Genome-Scale Metabolic Network models provides a theoretical framework to investigate cell metabolism under different constraints.

RESULTS: We have built new models for various S. lividans strains to better understand the mechanisms associated with overproduction of proteins secreted through the Tat route. We compare models of an S. lividans Tat-dependent agarase overproducing strain with those of the S. lividans wild-type, an S. lividans strain carrying the multi-copy plasmid vector and an α-amylase Sec-dependent overproducing strain. Using updated genomic, transcriptomic and experimental data we could extend existing S. lividans models and produce a new model which produces improved results largely extending the coverage of S. lividans strains, the number of genes and reactions being considered, the predictive behaviour and the dependence on specification of exchange constraints. Comparison of the optimized solutions obtained highlights numerous changes between Tat- and Sec-dependent protein secreting strains affecting the metabolism of carbon, amino acids, nucleotides, lipids and cofactors, and variability analysis predicts a large potential for protein overproduction.

CONCLUSIONS: This work provides a detailed look to metabolic changes associated to Tat-dependent protein secretion reproducing experimental observations and identifying changes that are specific to each secretory route, presenting a novel, improved, more accurate and strain-independent model of S. lividans, thus opening the way for enhanced metabolic engineering of protein overproduction in S. lividans.}, } @article {pmid29898663, year = {2018}, author = {Zeng, S and Bick, J and Ulbrich, SE and Bauersachs, S}, title = {Cell type-specific analysis of transcriptome changes in the porcine endometrium on Day 12 of pregnancy.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {459}, pmid = {29898663}, issn = {1471-2164}, mesh = {Animals ; Cluster Analysis ; Endometrium/*metabolism ; Estrogens/physiology ; Female ; Gene Expression Profiling ; Laser Capture Microdissection ; Pregnancy/*genetics/metabolism ; Prostaglandins/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; Signal Transduction ; Swine ; *Transcriptome ; }, abstract = {BACKGROUND: Along with trophoblast elongation (Days 10 to 12), estradiol is secreted in increasing amounts for recognition of pregnancy. Endometrial secretions driven by ovarian progesterone and conceptus signals are essential for conceptus growth and development. Results of transcriptome analyses of whole endometrial tissue samples in the pig indicated the need for cell type-specific endometrial gene expression analysis for a better understanding of transcriptome changes associated with establishment of pregnancy.

RESULTS: The most distinct transcriptome profile and the majority of differentially expressed genes (DEGs) were identified in luminal epithelium (LE). Many DEGs were found only in the cell type-specific analysis. The functional classification of DEGs identified in specific endometrial cell types revealed various distinct functions and pathways. Genes related to immune activation, estrogen signaling pathway, embryo development, and cell proliferation were upregulated in LE of pregnant gilts. Genes involved in sterol biosynthetic and metabolic processes and extracellular matrix were upregulated in stroma. Genes associated with cell communication such as via exosomes and vesicles were found as differential in LE, glandular epithelium (GE), and stroma (S).

CONCLUSIONS: This study revealed that conceptus signals induce different transcriptomic regulations in the endometrial compartments/cell types related to their specific function during recognition and establishment of pregnancy.}, } @article {pmid29898661, year = {2018}, author = {Mura-Jornet, I and Pimentel, C and Dantas, GPM and Petry, MV and González-Acuña, D and Barbosa, A and Lowther, AD and Kovacs, KM and Poulin, E and Vianna, JA}, title = {Chinstrap penguin population genetic structure: one or more populations along the Southern Ocean?.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {90}, pmid = {29898661}, issn = {1471-2148}, support = {INACH T_27-10//Chilean Antarctic Institute/International ; RT_12-14//Chilean Antarctic Institute/International ; 110060//FONDECYT/International ; 1150517//FONDECYT/International ; 482501/2013-8//National Council for Scientific and Technological Development/International ; INCT-APA 574018/2008-5//National Council for Scientific and Technological Development/International ; CGL2004-01348,//Spanish Ministry of Economy and Competitiveness/International ; CGL2007-60369//Spanish Ministry of Economy and Competitiveness/International ; CTM2011-24427//Spanish Ministry of Economy and Competitiveness/International ; CONICYT PIA ACT172065 GAB//Comisión Nacional de Investigación Científica y Tecnológica (CL)/International ; }, mesh = {Animals ; Antarctic Regions ; Bayes Theorem ; Cluster Analysis ; DNA, Mitochondrial/genetics ; Demography ; Female ; Genetic Variation ; *Genetics, Population ; Geography ; Haplotypes/genetics ; Islands ; Male ; Microsatellite Repeats ; *Oceans and Seas ; Spheniscidae/*genetics ; }, abstract = {BACKGROUND: Historical factors, demography, reproduction and dispersal are crucial in determining the genetic structure of seabirds. In the Antarctic marine environment, penguins are a major component of the avian biomass, dominant predators and important bioindicators of ecological change. Populations of chinstrap penguins have decreased in nearly all their breeding sites, and their range is expanding throughout the Antarctic Peninsula. Population genetic structure of this species has been studied in some colonies, but not between breeding colonies in the Antarctic Peninsula or at the species' easternmost breeding colony (Bouvetøya).

RESULTS: Connectivity, sex-biased dispersal, diversity, genetic structure and demographic history were studied using 12 microsatellite loci and a mitochondrial DNA region (HVRI) in 12 breeding colonies in the South Shetland Islands (SSI) and the Western Antarctic Peninsula (WAP), and one previously unstudied sub-Antarctic island, 3600 km away from the WAP (Bouvetøya). High genetic diversity, evidence of female bias-dispersal and a sign of population expansion after the last glacial maximum around 10,000 mya were detected. Limited population genetic structure and lack of isolation by distance throughout the region were found, along with no differentiation between the WAP and Bouvetøya (overall microsatellite F ST = 0.002, p = 0.273; mtDNA F ST = - 0.004, p = 0.766), indicating long distance dispersal. Therefore, genetic assignment tests could not assign individuals to their population(s) of origin. The most differentiated location was Georges Point, one of the southernmost breeding colonies of this species in the WAP.

CONCLUSIONS: The subtle differentiation found may be explained by some combination of low natal philopatric behavior, high rates of dispersal and/or generally high mobility among colonies of chinstrap penguins compared to other Pygoscelis species.}, } @article {pmid29898660, year = {2018}, author = {Nawaz, MA and Chen, C and Shireen, F and Zheng, Z and Sohail, H and Afzal, M and Ali, MA and Bie, Z and Huang, Y}, title = {Genome-wide expression profiling of leaves and roots of watermelon in response to low nitrogen.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {456}, pmid = {29898660}, issn = {1471-2164}, support = {CARS-25//China Agriculture Research System/ ; 31471919, 31201660//National Natural Science Foundation of China/ ; }, mesh = {Chlorophyll/genetics/metabolism ; Citrullus/chemistry/*genetics/growth & development/metabolism ; Cytokinins/genetics/metabolism ; Gene Expression Profiling ; Genome, Plant ; Membrane Transport Proteins/genetics/metabolism ; Nitrates/metabolism ; Nitrogen/analysis/*physiology ; Photosynthesis/genetics ; Plant Leaves/genetics/metabolism ; Plant Roots/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; Transcription Factors/genetics/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Nitrogen (N) is a key macronutrient required for plant growth and development. In this study, watermelon plants were grown under hydroponic conditions at 0.2 mM N, 4.5 mM N, and 9 mM N for 14 days.

RESULTS: Dry weight and photosynthetic assimilation at low N (0.2 mM) was reduced by 29 and 74% compared with high N (9 mM). The photochemical activity (Fv/Fm) was also reduced from 0.78 at high N to 0.71 at low N. The N concentration in the leaf, stem, and root of watermelon under low N conditions was reduced by 68, 104, and 108%, respectively compared with 9 mM N treatment after 14 days of N treatment. In the leaf tissues of watermelon grown under low N conditions, 9598 genes were differentially expressed, out of which 4533 genes (47.22%) were up-regulated whereas, 5065 genes (52.78%) were down-regulated compared with high N. Similarly in the root tissues, 3956 genes were differentially expressed, out of which 1605 genes were up-regulated (40.57%) and 2351 genes were down-regulated (59.43%), compared with high N. Our results suggest that leaf tissues are more sensitive to N deficiency compared with root tissues. The gene ontology (GO) analysis showed that the availability of N significantly affected 19 biological processes, 8 cell component metabolic pathways, and 3 molecular functions in the leaves; and 13 biological processes, 12 molecular functions, and 5 cell component metabolic pathways in the roots of watermelon. The low affinity nitrate transporters, high affinity nitrate transporters, ammonium transporters, genes related with nitrogen assimilation, and chlorophyll and photosynthesis were expressed differentially in response to low N. Three nitrate transporters (Cla010066, Cla009721, Cla012765) substantially responded to low nitrate supply in the root and leaf tissues. Additionally, a large number of transcription factors (1365) were involved in adaptation to low N availability. The major transcription factor families identified in this study includes MYB, AP2-EREBP, bHLH, C2H2 and NAC.

CONCLUSION: Candidate genes identified in this study for nitrate uptake and transport can be targeted and utilized for further studies in watermelon breeding and improvement programs to improve N uptake and utilization efficiency.}, } @article {pmid29898659, year = {2018}, author = {Ferrari, R and Kia, DA and Tomkins, JE and Hardy, J and Wood, NW and Lovering, RC and Lewis, PA and Manzoni, C}, title = {Stratification of candidate genes for Parkinson's disease using weighted protein-protein interaction network analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {452}, pmid = {29898659}, issn = {1471-2164}, support = {U41 HG002273/HG/NHGRI NIH HHS/United States ; MR/N026004/1//Medical Research Council/United Kingdom ; MR/L010933/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; 284//Alzheimer's Society/United Kingdom ; WT089698//Wellcome Trust/United Kingdom ; G-1307//Parkinson's UK/United Kingdom ; }, mesh = {Genes ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Parkinson Disease/*genetics ; *Protein Interaction Mapping ; Protein Interaction Maps ; Proteins/genetics ; }, abstract = {BACKGROUND: Genome wide association studies (GWAS) have helped identify large numbers of genetic loci that significantly associate with increased risk of developing diseases. However, translating genetic knowledge into understanding of the molecular mechanisms underpinning disease (i.e. disease-specific impacted biological processes) has to date proved to be a major challenge. This is primarily due to difficulties in confidently defining candidate genes at GWAS-risk loci. The goal of this study was to better characterize candidate genes within GWAS loci using a protein interactome based approach and with Parkinson's disease (PD) data as a test case.

RESULTS: We applied a recently developed Weighted Protein-Protein Interaction Network Analysis (WPPINA) pipeline as a means to define impacted biological processes, risk pathways and therein key functional players. We used previously established Mendelian forms of PD to identify seed proteins, and to construct a protein network for genetic Parkinson's and carried out functional enrichment analyses. We isolated PD-specific processes indicating 'mitochondria stressors mediated cell death', 'immune response and signaling', and 'waste disposal' mediated through 'autophagy'. Merging the resulting protein network with data from Parkinson's GWAS we confirmed 10 candidate genes previously selected by pure proximity and were able to nominate 17 novel candidate genes for sporadic PD.

CONCLUSIONS: With this study, we were able to better characterize the underlying genetic and functional architecture of idiopathic PD, thus validating WPPINA as a robust pipeline for the in silico genetic and functional dissection of complex disorders.}, } @article {pmid29898658, year = {2018}, author = {Shoguchi, E and Beedessee, G and Tada, I and Hisata, K and Kawashima, T and Takeuchi, T and Arakaki, N and Fujie, M and Koyanagi, R and Roy, MC and Kawachi, M and Hidaka, M and Satoh, N and Shinzato, C}, title = {Two divergent Symbiodinium genomes reveal conservation of a gene cluster for sunscreen biosynthesis and recently lost genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {458}, pmid = {29898658}, issn = {1471-2164}, mesh = {Amino Acids/biosynthesis ; Cyclohexanols/metabolism ; Dinoflagellida/classification/*genetics ; *Evolution, Molecular ; Gene Deletion ; Genes ; *Genome ; Multigene Family ; Phylogeny ; Repetitive Sequences, Amino Acid ; Symbiosis/genetics ; }, abstract = {BACKGROUND: The marine dinoflagellate, Symbiodinium, is a well-known photosynthetic partner for coral and other diverse, non-photosynthetic hosts in subtropical and tropical shallows, where it comprises an essential component of marine ecosystems. Using molecular phylogenetics, the genus Symbiodinium has been classified into nine major clades, A-I, and one of the reported differences among phenotypes is their capacity to synthesize mycosporine-like amino acids (MAAs), which absorb UV radiation. However, the genetic basis for this difference in synthetic capacity is unknown. To understand genetics underlying Symbiodinium diversity, we report two draft genomes, one from clade A, presumed to have been the earliest branching clade, and the other from clade C, in the terminal branch.

RESULTS: The nuclear genome of Symbiodinium clade A (SymA) has more gene families than that of clade C, with larger numbers of organelle-related genes, including mitochondrial transcription terminal factor (mTERF) and Rubisco. While clade C (SymC) has fewer gene families, it displays specific expansions of repeat domain-containing genes, such as leucine-rich repeats (LRRs) and retrovirus-related dUTPases. Interestingly, the SymA genome encodes a gene cluster for MAA biosynthesis, potentially transferred from an endosymbiotic red alga (probably of bacterial origin), while SymC has completely lost these genes.

CONCLUSIONS: Our analysis demonstrates that SymC appears to have evolved by losing gene families, such as the MAA biosynthesis gene cluster. In contrast to the conservation of genes related to photosynthetic ability, the terminal clade has suffered more gene family losses than other clades, suggesting a possible adaptation to symbiosis. Overall, this study implies that Symbiodinium ecology drives acquisition and loss of gene families.}, } @article {pmid29898657, year = {2018}, author = {Santos-Beneit, F}, title = {Genome sequencing analysis of Streptomyces coelicolor mutants that overcome the phosphate-depending vancomycin lethal effect.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {457}, pmid = {29898657}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; 098374//Wellcome Trust grant/ ; Vanrestrep-740080//European Union's Horizon 2020 research and innovation programme/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics ; Genes, Reporter ; Genome, Plant ; Microfluidic Analytical Techniques ; Muramidase/pharmacology ; *Mutation ; Phosphates/*physiology ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Streptomyces coelicolor/*drug effects/*genetics ; Vancomycin/pharmacology ; Vancomycin Resistance/*genetics ; }, abstract = {BACKGROUND: Glycopeptide antibiotics inhibit bacterial cell-wall synthesis, and are important for the treatment of infections caused by multi drug-resistant strains of enterococci, streptococci and staphylococci. The main mechanism by which bacteria resist the action of glycopeptides is by producing a modified cell-wall in which the dipeptide D-Alanine-D-Alanine is substituted by D-Alanine-D-Lactate or D-Alanine-D-Serine. Recently, it has been shown that inorganic phosphate (Pi) induces hypersensitivity to vancomycin in Streptomyces coelicolor (which is highly resistant to the antibiotic in low-Pi media). This finding was surprising because the bacterium possesses the entire set of genes responsible for vancomycin resistance (VR); including those coding for the histidine kinase/response regulator pair VanS/VanR that activates the system.

RESULTS: This work shows that high Pi amounts in the medium hamper the activation of the van promoters and consequently inhibit VR in S. coelicolor; i.e. the repression effect being stronger when basic or acidic forms of the nutrient are used. In addition, this work shows that lysozyme resistance is also highly regulated by the Pi concentration in the medium. At least five different mutations contribute to the overcoming of this repression effect over VR (but not over lysozyme resistance). Therefore, the interconnection of VR and lysozyme resistance mechanisms might be inexistent or complex. In particular, two kinds of mutant in which Pi control of VR has been lost (one class expresses the van genes in a constitutive manner; the other retains inducibility by vancomycin) have been isolated and further characterized in this study. Sequencing revealed that the first class of mutation conferred a single amino acid substitution in the second transmembrane helix of the VanS protein; whereas the other class hampered the expression or activity of a putative homolog (SCO1213) to the staphylococcal GatD protein. Complementation, phenotypic and bioinformatics analyses identified SCO1213, and its upstream gene (i.e. murT), as relevant genetic determinants involved with VR in S. coelicolor.

CONCLUSION: The genomic approach of this study together with other genetic and phenotypic analyses has allowed the identification of the uncharacterized murT-gatD Streptomyces genes and the characterization of their involvement with the Pi control of VR in S. coelicolor.}, } @article {pmid29898656, year = {2018}, author = {Bahri, BA and Daverdin, G and Xu, X and Cheng, JF and Barry, KW and Brummer, EC and Devos, KM}, title = {Natural variation in genes potentially involved in plant architecture and adaptation in switchgrass (Panicum virgatum L.).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {91}, pmid = {29898656}, issn = {1471-2148}, support = {DE-PS02-06ER64304//Office of Biological and Environmental Research in the Department of Energy (DOE) Office of Science to the BioEnergy Science Center (BESC)/International ; }, mesh = {Adaptation, Physiological/*genetics ; Base Sequence ; Biomass ; Chromosome Mapping ; Gene Flow ; *Genes, Plant ; *Genetic Variation ; Genetics, Population ; Mutation/genetics ; Panicum/*anatomy & histology/*genetics/physiology ; Phylogeography ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; United States ; }, abstract = {BACKGROUND: Advances in genomic technologies have expanded our ability to accurately and exhaustively detect natural genomic variants that can be applied in crop improvement and to increase our knowledge of plant evolution and adaptation. Switchgrass (Panicum virgatum L.), an allotetraploid (2n = 4× = 36) perennial C4 grass (Poaceae family) native to North America and a feedstock crop for cellulosic biofuel production, has a large potential for genetic improvement due to its high genotypic and phenotypic variation. In this study, we analyzed single nucleotide polymorphism (SNP) variation in 372 switchgrass genotypes belonging to 36 accessions for 12 genes putatively involved in biomass production to investigate signatures of selection that could have led to ecotype differentiation and to population adaptation to geographic zones.

RESULTS: A total of 11,682 SNPs were mined from ~ 15 Gb of sequence data, out of which 251 SNPs were retained after filtering. Population structure analysis largely grouped upland accessions into one subpopulation and lowland accessions into two additional subpopulations. The most frequent SNPs were in homozygous state within accessions. Sixty percent of the exonic SNPs were non-synonymous and, of these, 45% led to non-conservative amino acid changes. The non-conservative SNPs were largely in linkage disequilibrium with one haplotype being predominantly present in upland accessions while the other haplotype was commonly present in lowland accessions. Tajima's test of neutrality indicated that PHYB, a gene involved in photoperiod response, was under positive selection in the switchgrass population. PHYB carried a SNP leading to a non-conservative amino acid change in the PAS domain, a region that acts as a sensor for light and oxygen in signal transduction.

CONCLUSIONS: Several non-conservative SNPs in genes potentially involved in plant architecture and adaptation have been identified and led to population structure and genetic differentiation of ecotypes in switchgrass. We suggest here that PHYB is a key gene involved in switchgrass natural selection. Further analyses are needed to determine whether any of the non-conservative SNPs identified play a role in the differential adaptation of upland and lowland switchgrass.}, } @article {pmid29898655, year = {2018}, author = {Cheng, Z and Yu, X and Li, S and Wu, Q}, title = {Genome-wide transcriptome analysis and identification of benzothiadiazole-induced genes and pathways potentially associated with defense response in banana.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {454}, pmid = {29898655}, issn = {1471-2164}, support = {31701903//National Natural Science Foundation of China/ ; 31701484//National Natural Science Foundation of China/ ; }, mesh = {Cell Wall/metabolism ; Disease Resistance ; Fusarium/*physiology ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Genes, cdc ; Genome, Plant ; Musa/drug effects/*genetics/metabolism/microbiology ; Plant Diseases/genetics/*microbiology ; Plant Growth Regulators/biosynthesis/physiology ; Plant Proteins/biosynthesis/genetics ; Reactive Oxygen Species/metabolism ; Real-Time Polymerase Chain Reaction ; Secondary Metabolism/genetics ; Signal Transduction ; Thiadiazoles/*pharmacology ; Transcription Factors/genetics/metabolism ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: Bananas (Musa spp.) are the most important fruit crops worldwide due to their high nutrition value. Fusarium wilt of banana, caused by fungal pathogen Fusarium oxysporum f. sp. cubense tropical race 4 (Foc 4), is considered as the most destructive disease in the world and results in extensive damage leading to productivity loss. The widespread use of plant resistance inducers (PRIs), such as benzothiadiazole (BTH), is a novel strategy to stimulate defense responses in banana plants to protect against pathogens infection. The recent focus on the crop defense against fungal infections has led to a renewed interest on understanding the molecular mechanisms of specific PRIs-mediated resistance. This transcriptome study aimed to identify genes that are associated with BTH-induced resistance. Patterns of gene expression in the leaves and roots of BTH-sprayed banana plants were studied using RNA-Seq.

RESULTS: In this study, 18 RNA-Seq libraries from BTH-sprayed and untreated leaves and roots of the Cavendish plants, the most widely grown banana cultivar, were used for studying the transcriptional basis of BTH-related resistance. Comparative analyses have revealed that 6689 and 3624 differentially expressed genes were identified in leaves and roots, respectively, as compared to the control. Approximately 80% of these genes were differentially expressed in a tissue-specific manner. Further analysis showed that signaling perception and transduction, transcription factors, disease resistant proteins, plant hormones and cell wall organization-related genes were stimulated by BTH treatment, especially in roots. Interestingly, the ethylene and auxin biosynthesis and response genes were found to be up-regulated in leaves and roots, respectively, suggesting a choice among BTH-responsive phytohormone regulation.

CONCLUSIONS: Our data suggests a role for BTH in enhancing banana plant defense responses to Foc 4 infection, and demonstrates that BTH selectively affect biological processes associated with plant defenses. The genes identified in the study could be further studied and exploited to develop Foc 4-resistant banana varieties.}, } @article {pmid29898654, year = {2018}, author = {Morris, M and Shaw, A and Lambert, M and Perry, HH and Lowenstein, E and Valenzuela, D and Velazquez-Ulloa, NA}, title = {Developmental nicotine exposure affects larval brain size and the adult dopaminergic system of Drosophila melanogaster.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {13}, pmid = {29898654}, issn = {1471-213X}, support = {2014368:JAT:02/26/15//M.J. Murdock Charitable Trust/International ; 2014267:MNL:2/26/2015//M.J. Murdock Charitable Trust/International ; }, abstract = {BACKGROUND: Pregnant women may be exposed to nicotine if they smoke or use tobacco products, nicotine replacement therapy, or via e-cigarettes. Prenatal nicotine exposure has been shown to have deleterious effects on the nervous system in mammals including changes in brain size and in the dopaminergic system. The genetic and molecular mechanisms for these changes are not well understood. A Drosophila melanogaster model for these effects of nicotine exposure could contribute to faster identification of genes and molecular pathways underlying these effects. The purpose of this study was to determine if developmental nicotine exposure affects the nervous system of Drosophila melanogaster, focusing on changes to brain size and the dopaminergic system at two developmental stages.

RESULTS: We reared flies on control or nicotine food from egg to 3rd instar larvae or from egg to adult and determined effectiveness of the nicotine treatment. We used immunohistochemistry to visualize the whole brain and dopaminergic neurons, using tyrosine hydroxylase as the marker. We measured brain area, tyrosine hydroxylase fluorescence, and counted the number of dopaminergic neurons in brain clusters. We detected an increase in larval brain hemisphere area, a decrease in tyrosine hydroxylase fluorescence in adult central brains, and a decrease in the number of neurons in the PPM3 adult dopaminergic cluster. We tested involvement of Dα7, one of the nicotinic acetylcholine receptor subunits, and found it was involved in eclosion, as previously described, but not involved in brain size.

CONCLUSIONS: We conclude that developmental nicotine exposure in Drosophila melanogaster affects brain size and the dopaminergic system. Prenatal nicotine exposure in mammals has also been shown to have effects on brain size and in the dopaminergic system. This study further establishes Drosophila melanogaster as model organism to study the effects of developmental nicotine exposure. The genetic and molecular tools available for Drosophila research will allow elucidation of the mechanisms underlying the effects of nicotine exposure during development.}, } @article {pmid29898652, year = {2018}, author = {Lian, S and Liu, T and Jing, S and Yuan, H and Zhang, Z and Cheng, L}, title = {Intrachromosomal colocalization strengthens co-expression, co-modification and evolutionary conservation of neighboring genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {455}, pmid = {29898652}, issn = {1471-2164}, support = {61501392//National Natural Science Foundation of China/ ; U1604112//National Natural Science Foundation of China/ ; }, mesh = {Arabidopsis/genetics ; *Chromosomes, Plant ; *Evolution, Molecular ; *Gene Expression ; Gene Order ; Genes, Plant ; Histone Code ; }, abstract = {BACKGROUND: Gene order and location in chromosomes of species are non-random. Neighboring gene pairs tend to display some similarities, such as co-expression and co-modification. However, the contribution of linear proximity, spatial proximity, and evolutionary proximity to these similarities remain unclear, together with whether the presence of several types of proximity can strengthens the similarities.

RESULTS: In this study, we investigated the properties of three kinds of colocalized gene pairs: intrachromosomal colocalized gene pairs, always-neighboring gene pairs, and evolutionary neighboring gene pairs. Our analysis showed that (1) Different types of colocalized genes differentially contribute to co-expression, co-modifications and conservation across species; (2) Intrachromosomal colocalization can strengthen co-expression and co-modification of neighboring gene pairs and their conservation across species; (3) The combination of the three kinds of colocalization can lead to the strongest co-modification and is most strongly conserved across species. (4) Colocalized gene pairs are indicative of phylogenetic relationships and whole genome duplications (WGDs).

CONCLUSIONS: These results provide valuable clues for future efforts to understand the characteristics of colocalized gene pairs and how the neighborhood affects their interactions.}, } @article {pmid29898651, year = {2018}, author = {Díaz-Gay, M and Vila-Casadesús, M and Franch-Expósito, S and Hernández-Illán, E and Lozano, JJ and Castellví-Bel, S}, title = {Mutational Signatures in Cancer (MuSiCa): a web application to implement mutational signatures analysis in cancer samples.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {224}, pmid = {29898651}, issn = {1471-2105}, abstract = {BACKGROUND: Mutational signatures have been proved as a valuable pattern in somatic genomics, mainly regarding cancer, with a potential application as a biomarker in clinical practice. Up to now, several bioinformatic packages to address this topic have been developed in different languages/platforms. MutationalPatterns has arisen as the most efficient tool for the comparison with the signatures currently reported in the Catalogue of Somatic Mutations in Cancer (COSMIC) database. However, the analysis of mutational signatures is nowadays restricted to a small community of bioinformatic experts.

RESULTS: In this work we present Mutational Signatures in Cancer (MuSiCa), a new web tool based on MutationalPatterns and built using the Shiny framework in R language. By means of a simple interface suited to non-specialized researchers, it provides a comprehensive analysis of the somatic mutational status of the supplied cancer samples. It permits characterizing the profile and burden of mutations, as well as quantifying COSMIC-reported mutational signatures. It also allows classifying samples according to the above signature contributions.

CONCLUSIONS: MuSiCa is a helpful web application to characterize mutational signatures in cancer samples. It is accessible online at http://bioinfo.ciberehd.org/GPtoCRC/en/tools.html and source code is freely available at https://github.com/marcos-diazg/musica .}, } @article {pmid29897834, year = {2018}, author = {Wall, E and Majdalani, N and Gottesman, S}, title = {The Complex Rcs Regulatory Cascade.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {111-139}, doi = {10.1146/annurev-micro-090817-062640}, pmid = {29897834}, issn = {1545-3251}, abstract = {RcsB, a response regulator of the FixJ/NarL family, is at the center of a complex network of regulatory inputs and outputs. Cell surface stress is sensed by an outer membrane lipoprotein, RcsF, which regulates interactions of the inner membrane protein IgaA, lifting negative regulation of a phosphorelay. In vivo evidence supports a pathway in which histidine kinase RcsC transfers phosphate to phosphotransfer protein RcsD, resulting in phosphorylation of RcsB. RcsB acts either alone or in combination with RcsA to positively regulate capsule synthesis and synthesis of small RNA (sRNA) RprA as well as other genes, and to negatively regulate motility. RcsB in combination with other FixJ/NarL auxiliary proteins regulates yet other functions, independent of RcsB phosphorylation. Proper expression of Rcs and its targets is critical for success of Escherichia coli commensal strains, for proper development of biofilm, and for virulence in some pathogens. New understanding of how the Rcs phosphorelay works provides insight into the flexibility of the two-component system paradigm.}, } @article {pmid29897833, year = {2018}, author = {Le Roux, F and Blokesch, M}, title = {Eco-evolutionary Dynamics Linked to Horizontal Gene Transfer in Vibrios.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {89-110}, doi = {10.1146/annurev-micro-090817-062148}, pmid = {29897833}, issn = {1545-3251}, abstract = {Vibrio is a genus of ubiquitous heterotrophic bacteria found in aquatic environments. Although they are a small percentage of the bacteria in these environments, vibrios can predominate during blooms. Vibrios also play important roles in the degradation of polymeric substances, such as chitin, and in other biogeochemical processes. Vibrios can be found as free-living bacteria, attached to particles, or associated with other organisms in a mutualistic, commensal, or pathogenic relationship. This review focuses on vibrio ecology and genome plasticity, which confers an ability to adapt to new niches and is driven, at least in part, by horizontal gene transfer (HGT). The extent of HGT and its role in pathogen emergence are discussed based on genomic studies of environmental and pathogenic vibrios, mobile genetically encoded virulence factors, and mechanistic studies on the different modes of HGT.}, } @article {pmid29897809, year = {2018}, author = {Taborsky, B and Heino, M and Dieckmann, U}, title = {Life-History Multistability Caused by Size-Dependent Mortality.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {62-71}, doi = {10.1086/697412}, pmid = {29897809}, issn = {1537-5323}, abstract = {Body size is a key determinant of mortality risk. In natural populations, a broad range of relationships are observed between body size and mortality, including positive and negative correlations. Previous evolutionary modeling has shown that negatively size-dependent mortality can result in life-history bistability, with early maturation at small size and late maturation at large size representing alternative fitness optima. Here we present a general analysis of conditions under which such life-history bistabilities can occur, reporting the following findings. First, alternative fitness optima can be found for any arbitrarily chosen forms of mortality functions, including functions according to which mortality smoothly declines with size. Second, while bistabilities occur more readily under negatively size-dependent mortality, our analysis reveals that they can also emerge under positively size-dependent mortality, a feature missed in earlier work. Third, any sharp drop of mortality with size facilitates bistability. Fourth, if the mortality regime involves more than one such sharp drop, multistable life histories can occur, with alternative fitness optima straddling each of the drops. Paradoxically, our findings imply that, fifth, a species-poor predator community capable of creating a rugged mortality regime is conducive to evolutionary multistability, which could act as a stepping stone toward prey life-history diversification, whereas a species-rich predator community that results in a smoothly varying mortality regime may prevent diversification through this pathway.}, } @article {pmid29897808, year = {2018}, author = {Heath, JJ and Abbot, P and Stireman, JO}, title = {Adaptive Divergence in a Defense Symbiosis Driven from the Top Down.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {E21-E36}, doi = {10.1086/697446}, pmid = {29897808}, issn = {1537-5323}, abstract = {Most studies of adaptive radiation in animals focus on resource competition as the primary driver of trait divergence. The roles of other ecological interactions in shaping divergent phenotypes during such radiations have received less attention. We evaluate natural enemies as primary agents of diversifying selection on the phenotypes of an actively diverging lineage of gall midges on tall goldenrod. In this system, the gall of the midge consists of a biotrophic fungal symbiont that develops on host-plant leaves and forms distinctly variable protective carapaces over midge larvae. Through field studies, we show that fungal gall morphology, which is induced by midges (i.e., it is an extended phenotype), is under directional and diversifying selection by parasitoid enemies. Overall, natural enemies disruptively select for either small or large galls, mainly along the axis of gall thickness. These results imply that predators are driving the evolution of phenotypic diversity in symbiotic defense traits in this system and that divergence in defensive morphology may provide ecological opportunities that help to fuel the adaptive radiation of this genus of midges on goldenrods. This enemy-driven phenotypic divergence in a diversifying lineage illustrates the potential importance of consumer-resource and symbiotic species interactions in adaptive radiation.}, } @article {pmid29897807, year = {2018}, author = {Lymbery, RA and Kennington, WJ and Evans, JP}, title = {Multivariate Sexual Selection on Ejaculate Traits under Sperm Competition.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {94-104}, doi = {10.1086/697447}, pmid = {29897807}, issn = {1537-5323}, abstract = {The widespread prevalence of sperm competition means that ejaculates face intense sexual selection. However, prior investigations of sexual selection on gametes have been hampered by two difficulties: (1) deriving estimates of relative fitness from sperm competition trials that are comparable across rival male and female genotypes and (2) obtaining measures of competitive fertilization success that are not confounded by postzygotic effects. Here, we exploit the experimental tractability of a broadcast spawning marine invertebrate to overcome these challenges and characterize multivariate sexual selection on sperm traits when multiple ejaculates compete. In multimale spawning events, we tracked real-time success of sperm using fluorescent tags that are visible inside fertilized eggs. We then used multivariate selection analyses to identify patterns of linear and nonlinear sexual selection on multiple sperm morphology and motility traits. Specifically, we found nonlinear selection against divergent combinations of sperm length, velocity, and swimming path linearity. These patterns likely reflect the way different swimming strategies allow sperm to locate and track eggs. Our results demonstrate that there are overall patterns of selection on ejaculates across a biologically realistic range of ejaculate-ejaculate and ejaculate-female interactions; therefore, there is the potential for adaptive evolution of ejaculate traits under sperm competition.}, } @article {pmid29897806, year = {2018}, author = {McCombe, D and Ackerman, JD}, title = {Collector Motion Affects Particle Capture in Physical Models and in Wind Pollination.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {81-93}, doi = {10.1086/697551}, pmid = {29897806}, issn = {1537-5323}, abstract = {Particle capture is important for ecological processes in aquatic and terrestrial ecosystems. The current model is based on a stationary collector for which predictions about capture efficiency (η; flux of captured particles ∶ flux of particles) are based on the collector flow environment (i.e., collector Reynolds number, Rec; inertial force ∶ viscous force). This model does not account for the movement of collectors in nature. We examined the effect of collector motion (transverse and longitudinal to the flow) on η using a cylindrical model in the lab and the grass species Phleum pratense in the field. Collector motion increased η (up to 400% and 20% in the lab and field, respectively) and also affected the spatial distribution of particles on collectors, especially at low Rec. The effect was greatest for collectors moving transversely at large magnitude, which encountered more particles with higher relative momentum. These results, which differ from the stationary model, can be predicted by considering both Rec and the particle dynamics given by the Stokes number (Stk; particle stopping distance ∶ collector radius) and helped to resolve an existing controversy about pollination mechanisms. Collector motion should be considered in wind pollination and other ecological processes involving particle capture.}, } @article {pmid29897805, year = {2018}, author = {Runemark, A and Fernández, LP and Eroukhmanoff, F and Sætre, GP}, title = {Genomic Contingencies and the Potential for Local Adaptation in a Hybrid Species.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {10-22}, doi = {10.1086/697563}, pmid = {29897805}, issn = {1537-5323}, abstract = {Hybridization is increasingly recognized as a potent evolutionary force. Although additive genetic variation and novel combinations of parental genes theoretically increase the potential for hybrid species to adapt, few empirical studies have investigated the adaptive potential within a hybrid species. Here, we address whether genomic contingencies, adaptation to climate, or diet best explain divergence in beak morphology using genomically diverged island populations of the homoploid hybrid Italian sparrow Passer italiae from Crete, Corsica, and Sicily. Populations vary significantly in beak morphology both between and within islands of origin. Temperature seasonality best explains population divergence in beak size. Interestingly, beak shape along all significant dimensions of variation was best explained by annual precipitation, genomic composition, and their interaction, suggesting a role for contingencies. Moreover, beak shape similarity to a parent species correlates with proportion of the genome inherited from that species, consistent with the presence of contingencies. In conclusion, adaptation to local conditions and genomic contingencies arising from putatively independent hybridization events jointly explain beak morphology in the Italian sparrow. Hence, hybridization may induce contingencies and restrict evolution in certain directions dependent on the genetic background.}, } @article {pmid29897804, year = {2018}, author = {Gandon, S}, title = {Evolution and Manipulation of Vector Host Choice.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {23-34}, doi = {10.1086/697575}, pmid = {29897804}, issn = {1537-5323}, abstract = {The transmission of many animal and plant diseases relies on the behavior of arthropod vectors. In particular, the specific preference for infected or uninfected hosts observed in many vector species is expected to affect the circulation of vector-borne diseases. Here I develop a theoretical framework to study the epidemiology and evolution of the manipulation of host choice behavior of vectors. I show that vector preference strategies have dramatic epidemiological consequences. I also explore the evolution of vector host choice under different scenarios regarding control of the vector behavior by the pathogen. This analysis yields multiple evolutionary outcomes and explains the diversity of host choice behaviors observed in a broad range of vector-borne diseases. In particular, this analysis helps us understand why several pathogens have evolved manipulation strategies that vary with the infectious status of their vector species while other pathogens seem unable to evolve such complex conditional strategies. I argue that contrasting the behavior of infected and uninfected vectors is key to revealing the mechanistic constraints acting on the evolution of the manipulation of vector behavior.}, } @article {pmid29897803, year = {2018}, author = {Rogers, LA and Salomon, AK and Connors, B and Krkošek, M}, title = {Collapse, Tipping Points, and Spatial Demographic Structure Arising from the Adopted Migrant Life History.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {49-61}, doi = {10.1086/697488}, pmid = {29897803}, issn = {1537-5323}, abstract = {The roles of dispersal and recruitment have long been a focal point in ecology and conservation. The adopted migrant hypothesis proposes a life history in which social learning transmits migratory knowledge between generations of iteroparous fish. Specifically, juveniles disperse from the parental spawning site, encounter and recruit to a local adult population, and learn migration routes between spawning and foraging habitats by following older, experienced fish. Although the adopted migrant life history may apply to many species of pelagic marine fishes, there is scant theoretical or empirical work on the consequent population dynamics. We developed and analyzed a mathematical model of this life history in which the recruitment of juveniles depends on the relative abundance of the local populations and recruitment overlap, which measures the ease with which juveniles are recruited by a nonparental population. We demonstrate that the adopted migrant life history can maintain spatial demographic structure among local populations, that it can also predispose local populations to collapse when a tipping point is crossed, and that recovery after collapse is impaired by reduced recruitment at small local population sizes.}, } @article {pmid29897802, year = {2018}, author = {Zuk, M and Travisano, M}, title = {Models on the Runway: How Do We Make Replicas of the World?.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {1-9}, doi = {10.1086/697508}, pmid = {29897802}, issn = {1537-5323}, abstract = {Models are universal in science, both as theoretical formulations of reality and as model systems, representatives of other organisms. A recent paper on how scientists view the world divides our work into the mind, the lab, and the field and suggests that models must not be conflated with reality. But in practice, these distinctions are blurred. For example, are flour beetles a model system for other insects when their natural habitat is the same as the way they live in the lab? In addition, models can become restrictive when they are viewed as archetypes, making us overgeneralize about the world and ignoring meaningful variation. The study of sexual conflict in insects illustrates some of the pitfalls of relying on Drosophila as a model system for sexual selection. Microbes can be used as models for populations and communities and are essential parts of larger biological systems. Finally, some models are not meant to replicate the world but are worlds unto themselves in which diverse possibilities can be directly observed.}, } @article {pmid29897801, year = {2018}, author = {Schnedler-Meyer, NA and Pigolotti, S and Mariani, P}, title = {Evolution of Complex Asexual Reproductive Strategies in Jellyfish.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {72-80}, doi = {10.1086/697538}, pmid = {29897801}, issn = {1537-5323}, abstract = {Many living organisms in terrestrial and aquatic ecosystems rely on multiple reproductive strategies to reduce the risk of extinction in variable environments. Examples are provided by the polyp stage of several bloom-forming jellyfish species, which can reproduce asexually using different budding strategies. These strategies broadly fall into three categories: (1) fast localized reproduction, (2) dormant cysts, or (3) motile and dispersing buds. Similar functional strategies are also present in other groups of species. However, mechanisms leading to the evolution of this rich reproductive diversity are yet to be clarified. Here we model how risk of local population extinction and differential fitness of alternative modes of asexual reproduction could drive the evolution of multiple reproductive modes as seen in jellyfish polyps. Depending on environmental parameters, we find that evolution leads to a unique evolutionarily stable strategy, wherein multiple reproductive strategies generally coexist. As the extinction risk increases, this strategy shifts from a pure budding mode to a dual strategy and finally to one characterized by allocation into all three modes. We identify relative fitness-dependent thresholds in extinction risk where these transitions can occur and discuss our predictions in light of observations on polyp reproduction in laboratory and natural systems.}, } @article {pmid29897800, year = {2018}, author = {Ellner, SP}, title = {Generation Time in Structured Populations.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {105-110}, doi = {10.1086/697539}, pmid = {29897800}, issn = {1537-5323}, abstract = {Generation time is an intuitively simple concept, but for structured populations there are multiple definitions and no general understanding of how they relate to each other. François Bienvenu and Stéphane Legendre, in their note "A New Approach to the Generation Time in Matrix Population Models," appearing in the June 2015 issue of The American Naturalist, introduced a new measure of generation time Ta, the average time between birth events in an ancestral lineage, and derived the remarkably simple formula [Formula: see text] for any matrix model, where F is the fecundity matrix, v is reproductive value, and w is stable population structure. Here I generalize their formula and interpretations of Ta to a continuous or continuous-discrete population structure and derive similar formulas for three other established generation time measures: average parent age across all births at one time ([Formula: see text]) and mean parent age at birth events for a cohort (μ1) or generation (Tc). The new formulas reveal that these differently defined measures are unexpectedly often identical in value and clarify when they differ.}, } @article {pmid29897799, year = {2018}, author = {Hellström, L and Carlsson, L and Falster, DS and Westoby, M and Brännström, Å}, title = {Branch Thinning and the Large-Scale, Self-Similar Structure of Trees.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {E37-E47}, doi = {10.1086/697429}, pmid = {29897799}, issn = {1537-5323}, abstract = {Branch formation in trees has an inherent tendency toward exponential growth, but exponential growth in the number of branches cannot continue indefinitely. It has been suggested that trees balance this tendency toward expansion by also losing branches grown in previous growth cycles. Here, we present a model for branch formation and branch loss during ontogeny that builds on the phenomenological assumption of a branch carrying capacity. The model allows us to derive approximate analytical expressions for the number of tips on a branch, the distribution of growth modules within a branch, and the rate and size distribution of tree wood litter produced. Although limited availability of data makes empirical corroboration challenging, we show that our model can fit field observations of red maple (Acer rubrum) and note that the age distribution of discarded branches predicted by our model is qualitatively similar to an empirically observed distribution of dead and abscised branches of balsam poplar (Populus balsamifera). By showing how a simple phenomenological assumption-that the number of branches a tree can maintain is limited-leads directly to predictions on branching structure and the rate and size distribution of branch loss, these results potentially enable more explicit modeling of woody tissues in ecosystems worldwide, with implications for the buildup of flammable fuel, nutrient cycling, and understanding of plant growth.}, } @article {pmid29897798, year = {2018}, author = {Chisholm, RH and Connelly, BD and Kerr, B and Tanaka, MM}, title = {The Role of Pleiotropy in the Evolutionary Maintenance of Positive Niche Construction.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {35-48}, doi = {10.1086/697471}, pmid = {29897798}, issn = {1537-5323}, abstract = {Organisms often modify their environments to their advantage through a process of niche construction. Environments that are improved through positive niche construction can be viewed as a public good. If free riders appear that do not contribute to the shared resource and therefore do not incur any associated costs, the constructed niche may become degraded, resulting in a tragedy of the commons and the extinction of niche constructors. Niche construction can persist if free riders are excluded, for example, if niche constructors monopolize the resource they produce to a sufficient degree. We suggest, however, that the problem of free riders remains because it is possible that nonniche constructors with an enhanced ability to access the resource appear and invade a population of constructors. Using mathematical models we show that positive niche construction can be maintained if it is inextricably linked to a mechanism that makes free riding costly, such as a trait that confers a benefit to only niche constructors. We discuss this finding in terms of genetic interactions and illustrate the principle with a two-locus model. We conclude that positive niche construction can both evolve and be maintained when it has other beneficial effects via pleiotropy. This situation may apply generally to the evolutionary maintenance of cooperation.}, } @article {pmid29897797, year = {2018}, author = {Branco, P and Egas, M and Elser, JJ and Huisman, J}, title = {Eco-Evolutionary Dynamics of Ecological Stoichiometry in Plankton Communities.}, journal = {The American naturalist}, volume = {192}, number = {1}, pages = {E1-E20}, doi = {10.1086/697472}, pmid = {29897797}, issn = {1537-5323}, abstract = {Nitrogen (N) and phosphorus (P) limit primary production in many aquatic ecosystems, with major implications for ecological interactions in plankton communities. Yet it remains unclear how evolution may affect the N∶P stoichiometry of phytoplankton-zooplankton interactions. Here, we address this issue by analyzing an eco-evolutionary model of phytoplankton-zooplankton interactions with explicit nitrogen and phosphorus dynamics. In our model, investment of phytoplankton in nitrogen versus phosphorus uptake is an evolving trait, and zooplankton display selectivity for phytoplankton with N∶P ratios matching their nutritional requirements. We use this model to explore implications of the contrasting N∶P requirements of copepods versus cladocerans. The model predicts that selective zooplankton strongly affect the N∶P ratio of phytoplankton, resulting in deviations from their optimum N∶P ratio. Specifically, selective grazing by nitrogen-demanding copepods favors dominance of phytoplankton with low N∶P ratios, whereas phosphorus-demanding cladocerans favor dominance of phytoplankton with high N∶P ratios. Interestingly, selective grazing by nutritionally balanced zooplankton leads to the occurrence of alternative stable states, where phytoplankton may evolve either low, optimum, or high N∶P ratios, depending on the initial conditions. These results offer a new perspective on commonly observed differences in N∶P stoichiometry between plankton of freshwater and those of marine ecosystems and indicate that selective grazing by zooplankton can have a major impact on the stoichiometric composition of phytoplankton.}, } @article {pmid29897475, year = {2018}, author = {Kostka, D and Holloway, AK and Pollard, KS}, title = {Developmental Loci Harbor Clusters of Accelerated Regions That Evolved Independently in Ape Lineages.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2034-2045}, pmid = {29897475}, issn = {1537-1719}, support = {R01 GM082901/GM/NIGMS NIH HHS/United States ; R01 GM115836/GM/NIGMS NIH HHS/United States ; }, abstract = {Some of the fastest evolving regions of the human genome are conserved noncoding elements with many human-specific DNA substitutions. These human accelerated regions (HARs) are enriched nearby regulatory genes, and several HARs function as developmental enhancers. To investigate if this evolutionary signature is unique to humans, we quantified evidence of accelerated substitutions in conserved genomic elements across multiple lineages and applied this approach simultaneously to the genomes of five apes: human, chimpanzee, gorilla, orangutan, and gibbon. We find roughly similar numbers and genomic distributions of lineage-specific accelerated regions (linARs) in all five apes. In particular, apes share an enrichment of linARs in regulatory DNA nearby genes involved in development, especially transcription factors and other regulators. Many developmental loci harbor clusters of nonoverlapping linARs from multiple apes, suggesting that accelerated evolution in each species affected distinct regulatory elements that control a shared set of developmental pathways. Our statistical tests distinguish between GC-biased and unbiased accelerated substitution rates, allowing us to quantify the roles of different evolutionary forces in creating linARs. We find evidence of GC-biased gene conversion in each ape, but unbiased acceleration consistent with positive selection or loss of constraint is more common in all five lineages. It therefore appears that similar evolutionary processes created independent accelerated regions in the genomes of different apes, and that these lineage-specific changes to conserved noncoding sequences may have differentially altered expression of a core set of developmental genes across ape evolution.}, } @article {pmid29897459, year = {2018}, author = {Ghiselli, F and Iannello, M and Puccio, G and Chang, PL and Plazzi, F and Nuzhdin, SV and Passamonti, M}, title = {Comparative Transcriptomics in Two Bivalve Species Offers Different Perspectives on the Evolution of Sex-Biased Genes.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1389-1402}, pmid = {29897459}, issn = {1759-6653}, support = {R01 GM098741/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bivalvia/*genetics ; Evolution, Molecular ; Female ; Genomics/methods ; Male ; Sex Characteristics ; Transcriptome/*genetics ; }, abstract = {Comparative genomics has become a central tool for evolutionary biology, and a better knowledge of understudied taxa represents the foundation for future work. In this study, we characterized the transcriptome of male and female mature gonads in the European clam Ruditapes decussatus, compared with that in the Manila clam Ruditapes philippinarum providing, for the first time in bivalves, information about transcription dynamics and sequence evolution of sex-biased genes. In both the species, we found a relatively low number of sex-biased genes (1,284, corresponding to 41.3% of the orthologous genes between the two species), probably due to the absence of sexual dimorphism, and the transcriptional bias is maintained in only 33% of the orthologs. The dN/dS is generally low, indicating purifying selection, with genes where the female-biased transcription is maintained between the two species showing a significantly higher dN/dS. Genes involved in embryo development, cell proliferation, and maintenance of genome stability show a faster sequence evolution. Finally, we report a lack of clear correlation between transcription level and evolutionary rate in these species, in contrast with studies that reported a negative correlation. We discuss such discrepancy and call into question some methodological approaches and rationales generally used in this type of comparative studies.}, } @article {pmid29897326, year = {2018}, author = {Lee, I and Nam, H}, title = {Identification of drug-target interaction by a random walk with restart method on an interactome network.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {208}, pmid = {29897326}, issn = {1471-2105}, abstract = {BACKGROUND: Identification of drug-target interactions acts as a key role in drug discovery. However, identifying drug-target interactions via in-vitro, in-vivo experiments are very laborious, time-consuming. Thus, predicting drug-target interactions by using computational approaches is a good alternative. In recent studies, many feature-based and similarity-based machine learning approaches have shown promising results in drug-target interaction predictions. A previous study showed that accounting connectivity information of drug-drug and protein-protein interactions increase performances of prediction by the concept of 'guilt-by-association'. However, the approach that only considers directly connected nodes often misses the information that could be derived from distance nodes. Therefore, in this study, we yield global network topology information by using a random walk with restart algorithm and apply the global topology information to the prediction model.

RESULTS: As a result, our prediction model demonstrates increased prediction performance compare to the 'guilt-by-association' approach (AUC 0.89 and 0.67 in the training and independent test, respectively). In addition, we show how weighted features by a random walk with restart yields better performances than original features. Also, we confirmed that drugs and proteins that have high-degree of connectivity on the interactome network yield better performance in our model.

CONCLUSIONS: The prediction models with weighted features by considering global network topology increased the prediction performances both in the training and testing compared to non-weighted models and previous a 'guilt-by-association method'. In conclusion, global network topology information on protein-protein interaction and drug-drug interaction effects to the prediction performance of drug-target interactions.}, } @article {pmid29897325, year = {2018}, author = {Kim, M and Baek, SH and Song, M}, title = {Relation extraction for biological pathway construction using node2vec.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {206}, pmid = {29897325}, issn = {1471-2105}, abstract = {BACKGROUND: Systems biology is an important field for understanding whole biological mechanisms composed of interactions between biological components. One approach for understanding complex and diverse mechanisms is to analyze biological pathways. However, because these pathways consist of important interactions and information on these interactions is disseminated in a large number of biomedical reports, text-mining techniques are essential for extracting these relationships automatically.

RESULTS: In this study, we applied node2vec, an algorithmic framework for feature learning in networks, for relationship extraction. To this end, we extracted genes from paper abstracts using pkde4j, a text-mining tool for detecting entities and relationships. Using the extracted genes, a co-occurrence network was constructed and node2vec was used with the network to generate a latent representation. To demonstrate the efficacy of node2vec in extracting relationships between genes, performance was evaluated for gene-gene interactions involved in a type 2 diabetes pathway. Moreover, we compared the results of node2vec to those of baseline methods such as co-occurrence and DeepWalk.

CONCLUSIONS: Node2vec outperformed existing methods in detecting relationships in the type 2 diabetes pathway, demonstrating that this method is appropriate for capturing the relatedness between pairs of biological entities involved in biological pathways. The results demonstrated that node2vec is useful for automatic pathway construction.}, } @article {pmid29897324, year = {2018}, author = {Yu, MS and Lee, HM and Park, A and Park, C and Ceong, H and Rhee, KH and Na, D}, title = {In silico prediction of potential chemical reactions mediated by human enzymes.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {207}, pmid = {29897324}, issn = {1471-2105}, abstract = {BACKGROUND: Administered drugs are often converted into an ineffective or activated form by enzymes in our body. Conventional in silico prediction approaches focused on therapeutically important enzymes such as CYP450. However, there are more than thousands of different cellular enzymes that potentially convert administered drug into other forms.

RESULT: We developed an in silico model to predict which of human enzymes including metabolic enzymes as well as CYP450 family can catalyze a given chemical compound. The prediction is based on the chemical and physical similarity between known enzyme substrates and a query chemical compound. Our in silico model was developed using multiple linear regression and the model showed high performance (AUC = 0.896) despite of the large number of enzymes. When evaluated on a test dataset, it also showed significantly high performance (AUC = 0.746). Interestingly, evaluation with literature data showed that our model can be used to predict not only enzymatic reactions but also drug conversion and enzyme inhibition.

CONCLUSION: Our model was able to predict enzymatic reactions of a query molecule with a high accuracy. This may foster to discover new metabolic routes and to accelerate the computational development of drug candidates by enabling the prediction of the potential conversion of administered drugs into active or inactive forms.}, } @article {pmid29897323, year = {2018}, author = {Jiang, K and Feng, S and Song, Q and Calix, RA and Gupta, M and Bernard, GR}, title = {Identifying tweets of personal health experience through word embedding and LSTM neural network.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {210}, pmid = {29897323}, issn = {1471-2105}, support = {R15 LM011999/LM/NLM NIH HHS/United States ; }, abstract = {BACKGROUND: As Twitter has become an active data source for health surveillance research, it is important that efficient and effective methods are developed to identify tweets related to personal health experience. Conventional classification algorithms rely on features engineered by human domain experts, and engineering such features is a challenging task and requires much human intelligence. The resultant features may not be optimal for the classification problem, and can make it challenging for conventional classifiers to correctly predict personal experience tweets (PETs) due to the various ways to express and/or describe personal experience in tweets. In this study, we developed a method that combines word embedding and long short-term memory (LSTM) model without the need to engineer any specific features. Through word embedding, tweet texts were represented as dense vectors which in turn were fed to the LSTM neural network as sequences.

RESULTS: Statistical analyses of the results of 10-fold cross-validations of our method and conventional methods indicate that there exist significant differences (p < 0.01) in performance measures of accuracy, precision, recall, F1-score, and ROC/AUC, demonstrating that our approach outperforms the conventional methods in identifying PETs.

CONCLUSION: We presented an efficient and effective method of identifying health-related personal experience tweets by combining word embedding and an LSTM neural network. It is conceivable that our method can help accelerate and scale up analyzing textual data of social media for health surveillance purposes, because of no need for the laborious and costly process of engineering features.}, } @article {pmid29897322, year = {2018}, author = {Noh, K and Yoo, S and Lee, D}, title = {A systematic approach to identify therapeutic effects of natural products based on human metabolite information.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {205}, pmid = {29897322}, issn = {1471-2105}, abstract = {BACKGROUND: Natural products have been widely investigated in the drug development field. Their traditional use cases as medicinal agents and their resemblance of our endogenous compounds show the possibility of new drug development. Many researchers have focused on identifying therapeutic effects of natural products, yet the resemblance of natural products and human metabolites has been rarely touched.

METHODS: We propose a novel method which predicts therapeutic effects of natural products based on their similarity with human metabolites. In this study, we compare the structure, target and phenotype similarities between natural products and human metabolites to capture molecular and phenotypic properties of both compounds. With the generated similarity features, we train support vector machine model to identify similar natural product and human metabolite pairs. The known functions of human metabolites are then mapped to the paired natural products to predict their therapeutic effects.

RESULTS: With our selected three feature sets, structure, target and phenotype similarities, our trained model successfully paired similar natural products and human metabolites. When applied to the natural product derived drugs, we could successfully identify their indications with high specificity and sensitivity. We further validated the found therapeutic effects of natural products with the literature evidence.

CONCLUSIONS: These results suggest that our model can match natural products to similar human metabolites and provide possible therapeutic effects of natural products. By utilizing the similar human metabolite information, we expect to find new indications of natural products which could not be covered by previous in silico methods.}, } @article {pmid29897321, year = {2018}, author = {Gupta, S and Pawar, S and Ramrakhiyani, N and Palshikar, GK and Varma, V}, title = {Semi-Supervised Recurrent Neural Network for Adverse Drug Reaction mention extraction.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {212}, pmid = {29897321}, issn = {1471-2105}, abstract = {BACKGROUND: Social media is a useful platform to share health-related information due to its vast reach. This makes it a good candidate for public-health monitoring tasks, specifically for pharmacovigilance. We study the problem of extraction of Adverse-Drug-Reaction (ADR) mentions from social media, particularly from Twitter. Medical information extraction from social media is challenging, mainly due to short and highly informal nature of text, as compared to more technical and formal medical reports.

METHODS: Current methods in ADR mention extraction rely on supervised learning methods, which suffer from labeled data scarcity problem. The state-of-the-art method uses deep neural networks, specifically a class of Recurrent Neural Network (RNN) which is Long-Short-Term-Memory network (LSTM). Deep neural networks, due to their large number of free parameters rely heavily on large annotated corpora for learning the end task. But in the real-world, it is hard to get large labeled data, mainly due to the heavy cost associated with the manual annotation.

RESULTS: To this end, we propose a novel semi-supervised learning based RNN model, which can leverage unlabeled data also present in abundance on social media. Through experiments we demonstrate the effectiveness of our method, achieving state-of-the-art performance in ADR mention extraction.

CONCLUSION: In this study, we tackle the problem of labeled data scarcity for Adverse Drug Reaction mention extraction from social media and propose a novel semi-supervised learning based method which can leverage large unlabeled corpus available in abundance on the web. Through empirical study, we demonstrate that our proposed method outperforms fully supervised learning based baseline which relies on large manually annotated corpus for a good performance.}, } @article {pmid29897320, year = {2018}, author = {Jo, Y and Kim, S and Lee, D}, title = {Identification of common coexpression modules based on quantitative network comparison.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {213}, pmid = {29897320}, issn = {1471-2105}, abstract = {BACKGROUND: Finding common molecular interactions from different samples is essential work to understanding diseases and other biological processes. Coexpression networks and their modules directly reflect sample-specific interactions among genes. Therefore, identification of common coexpression network or modules may reveal the molecular mechanism of complex disease or the relationship between biological processes. However, there has been no quantitative network comparison method for coexpression networks and we examined previous methods for other networks that cannot be applied to coexpression network. Therefore, we aimed to propose quantitative comparison methods for coexpression networks and to find common biological mechanisms between Huntington's disease and brain aging by the new method.

RESULTS: We proposed two similarity measures for quantitative comparison of coexpression networks. Then, we performed experiments using known coexpression networks. We showed the validity of two measures and evaluated threshold values for similar coexpression network pairs from experiments. Using these similarity measures and thresholds, we quantitatively measured the similarity between disease-specific and aging-related coexpression modules and found similar Huntington's disease-aging coexpression module pairs.

CONCLUSIONS: We identified similar Huntington's disease-aging coexpression module pairs and found that these modules are related to brain development, cell death, and immune response. It suggests that up-regulated cell signalling related cell death and immune/ inflammation response may be the common molecular mechanisms in the pathophysiology of HD and normal brain aging in the frontal cortex.}, } @article {pmid29897319, year = {2018}, author = {Grant, RN and Kucher, D and León, AM and Gemmell, JF and Raicu, DS and Fodeh, SJ}, title = {Automatic extraction of informal topics from online suicidal ideation.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {211}, pmid = {29897319}, issn = {1471-2105}, abstract = {BACKGROUND: Suicide is an alarming public health problem accounting for a considerable number of deaths each year worldwide. Many more individuals contemplate suicide. Understanding the attributes, characteristics, and exposures correlated with suicide remains an urgent and significant problem. As social networking sites have become more common, users have adopted these sites to talk about intensely personal topics, among them their thoughts about suicide. Such data has previously been evaluated by analyzing the language features of social media posts and using factors derived by domain experts to identify at-risk users.

RESULTS: In this work, we automatically extract informal latent recurring topics of suicidal ideation found in social media posts. Our evaluation demonstrates that we are able to automatically reproduce many of the expertly determined risk factors for suicide. Moreover, we identify many informal latent topics related to suicide ideation such as concerns over health, work, self-image, and financial issues.

CONCLUSIONS: These informal topics topics can be more specific or more general. Some of our topics express meaningful ideas not contained in the risk factors and some risk factors do not have complimentary latent topics. In short, our analysis of the latent topics extracted from social media containing suicidal ideations suggests that users of these systems express ideas that are complementary to the topics defined by experts but differ in their scope, focus, and precision of language.}, } @article {pmid29897318, year = {2018}, author = {Suárez-Paniagua, V and Segura-Bedmar, I}, title = {Evaluation of pooling operations in convolutional architectures for drug-drug interaction extraction.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 8}, pages = {209}, pmid = {29897318}, issn = {1471-2105}, abstract = {BACKGROUND: Deep Neural Networks (DNN), in particular, Convolutional Neural Networks (CNN), has recently achieved state-of-art results for the task of Drug-Drug Interaction (DDI) extraction. Most CNN architectures incorporate a pooling layer to reduce the dimensionality of the convolution layer output, preserving relevant features and removing irrelevant details. All the previous CNN based systems for DDI extraction used max-pooling layers.

RESULTS: In this paper, we evaluate the performance of various pooling methods (in particular max-pooling, average-pooling and attentive pooling), as well as their combination, for the task of DDI extraction. Our experiments show that max-pooling exhibits a higher performance in F1-score (64.56%) than attentive pooling (59.92%) and than average-pooling (58.35%).

CONCLUSIONS: Max-pooling outperforms the others alternatives because is the only one which is invariant to the special pad tokens that are appending to the shorter sentences known as padding. Actually, the combination of max-pooling and attentive pooling does not improve the performance as compared with the single max-pooling technique.}, } @article {pmid29896860, year = {2018}, author = {Schamberg, I and Wittig, RM and Crockford, C}, title = {Call type signals caller goal: a new take on ultimate and proximate influences in vocal production.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {2071-2082}, doi = {10.1111/brv.12437}, pmid = {29896860}, issn = {1469-185X}, abstract = {After 40 years of debate it remains unclear whether signallers produce vocalizations in order to provide receivers with information about call context or external stimuli. This has led some researchers to propose that call production is arousal- or affect-based. Although arousal influences certain acoustic parameters within a call type, we argue that it cannot explain why individuals across vertebrates produce different call types. Given emerging evidence that calls are goal-based, we argue that call type is a signal of a caller's goal to elicit a change in receiver behaviour. Using chimpanzees (Pan troglodytes) and vervet monkeys (Cercopithecus aethiops) as case studies, we demonstrate the two benefits of viewing call production as signalling both caller goal (which determines call type) and caller arousal (which affects within-call-type variation). Such a framework can explain first, why a single class of calls is apparently given in multiple contexts, and, second, why some species have larger call repertoires than others. Previous studies have noted links between sociality and repertoire size, but have not specified exactly why animals living in societies that are more complex might require a greater number of differentiated signals. The caller-goal framework potentially clarifies how social complexity might favour call diversification. As social complexity increases, callers may need to elicit a larger number of distinct behaviours from a wider range of distinct audiences.}, } @article {pmid29895959, year = {2018}, author = {Swidergall, M and Solis, NV and Lionakis, MS and Filler, SG}, title = {Author Correction: EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1074}, doi = {10.1038/s41564-018-0188-5}, pmid = {29895959}, issn = {2058-5276}, abstract = {In the version of this Article originally published, the authors described the ANT compound used in their study as 4-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzoic acid (ANT). The authors now wish to clarify that the ANT compound used was actually a 2,5-dimethylpyrrolyl benzoic acid derivative1 that has been shown to inhibit not only the enzymatic activity of EphA2, but also several unrelated enzymes2. The description of the compound in the Article has now been changed to 4-(2,5-dimethyl-1H-pyrrol-1-yl)-2-hydroxybenzoic acid derivative (ANT) to reflect this.}, } @article {pmid29895928, year = {2018}, author = {}, title = {China sets a strong example on how to address scientific fraud.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {162}, doi = {10.1038/d41586-018-05417-1}, pmid = {29895928}, issn = {1476-4687}, mesh = {Biomedical Research ; China ; *Fraud ; Research ; *Scientific Misconduct ; }, } @article {pmid29895927, year = {2018}, author = {}, title = {The phrase 'necessary and sufficient' blamed for flawed neuroscience.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {162}, doi = {10.1038/d41586-018-05418-0}, pmid = {29895927}, issn = {1476-4687}, mesh = {*Logic ; *Neurosciences ; Research Design ; }, } @article {pmid29895926, year = {2018}, author = {Reardon, S}, title = {FARC and the forest: Peace is destroying Colombia's jungle - and opening it to science.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {169-170}, doi = {10.1038/d41586-018-05397-2}, pmid = {29895926}, issn = {1476-4687}, mesh = {Agriculture/*trends ; Animal Migration ; Animals ; *Biodiversity ; Colombia ; Conservation of Natural Resources/economics/*trends ; Ecology/economics/*trends ; Environmental Policy/economics/legislation & jurisprudence/trends ; Forestry/*trends ; *Forests ; Mining/*trends ; Research/*trends ; Warfare ; }, } @article {pmid29895925, year = {2018}, author = {Butler, D}, title = {Speedy Ebola tests help contain Africa's latest outbreak.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {172}, doi = {10.1038/d41586-018-05389-2}, pmid = {29895925}, issn = {1476-4687}, mesh = {Contact Tracing ; Democratic Republic of the Congo/epidemiology ; Disease Outbreaks/*prevention & control ; Ebolavirus/*genetics/*isolation & purification ; Hemorrhagic Fever, Ebola/*diagnosis/epidemiology/*prevention & control/transmission ; Humans ; Mass Screening/economics/*methods ; Quarantine ; Time Factors ; }, } @article {pmid29895922, year = {2018}, author = {Reardon, S}, title = {Faecal transplants could help preserve vulnerable species.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {173-174}, doi = {10.1038/d41586-018-05352-1}, pmid = {29895922}, issn = {1476-4687}, mesh = {Animals ; Animals, Wild/microbiology ; Animals, Zoo/microbiology ; Anura/microbiology ; Conservation of Natural Resources/*methods ; Diet/*veterinary ; *Endangered Species ; Eucalyptus ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; *Food Preferences ; Gastrointestinal Microbiome/*physiology ; Male ; Mycoses/microbiology/prevention & control/veterinary ; Perissodactyla/*microbiology/physiology ; Phascolarctidae/*microbiology/physiology ; Survival Rate ; }, } @article {pmid29895920, year = {2018}, author = {}, title = {Physicists cheer rendezvous of Higgs boson and top quark.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {164}, doi = {10.1038/d41586-018-05348-x}, pmid = {29895920}, issn = {1476-4687}, } @article {pmid29895919, year = {2018}, author = {}, title = {A simple test helps pinpoint a baby's arrival date.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {165}, doi = {10.1038/d41586-018-05350-3}, pmid = {29895919}, issn = {1476-4687}, } @article {pmid29895918, year = {2018}, author = {Cyranoski, D}, title = {China introduces sweeping reforms to crack down on academic misconduct.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {171}, doi = {10.1038/d41586-018-05359-8}, pmid = {29895918}, issn = {1476-4687}, mesh = {China ; *Ethics, Research ; Peer Review, Research/ethics/legislation & jurisprudence/standards ; Periodicals as Topic/ethics/legislation & jurisprudence/*standards ; Plagiarism ; Research/legislation & jurisprudence/*standards ; Research Personnel/ethics/*legislation & jurisprudence/*standards ; Scientific Misconduct/*legislation & jurisprudence ; Social Justice ; }, } @article {pmid29895917, year = {2018}, author = {}, title = {The sea creature that swallows its food whole - twice.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {165}, doi = {10.1038/d41586-018-05396-3}, pmid = {29895917}, issn = {1476-4687}, } @article {pmid29895916, year = {2018}, author = {}, title = {Cloak conceals contents from magnetic 'eyes'.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {165}, doi = {10.1038/d41586-018-05349-w}, pmid = {29895916}, issn = {1476-4687}, } @article {pmid29895915, year = {2018}, author = {Tollefson, J}, title = {Sucking carbon dioxide from air is cheaper than scientists thought.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {173}, doi = {10.1038/d41586-018-05357-w}, pmid = {29895915}, issn = {1476-4687}, } @article {pmid29895914, year = {2018}, author = {}, title = {How Easter Island's stone heads got their huge hats.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {164}, doi = {10.1038/d41586-018-05347-y}, pmid = {29895914}, issn = {1476-4687}, } @article {pmid29895913, year = {2018}, author = {}, title = {Saving the climate without sacrifice.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {164-165}, doi = {10.1038/d41586-018-05344-1}, pmid = {29895913}, issn = {1476-4687}, } @article {pmid29895912, year = {2018}, author = {}, title = {Fastidious apes turn up their noses at filthy food.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {165}, doi = {10.1038/d41586-018-05337-0}, pmid = {29895912}, issn = {1476-4687}, } @article {pmid29895911, year = {2018}, author = {Deniz, AA}, title = {Enzymes can adapt to cold by wiggling regions far from their active site.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {195-196}, doi = {10.1038/d41586-018-05302-x}, pmid = {29895911}, issn = {1476-4687}, mesh = {*Biochemistry ; Biophysical Phenomena ; Biophysics ; *Catalytic Domain ; Enzymes ; }, } @article {pmid29895910, year = {2018}, author = {}, title = {Glow-in-the-dark semiconductor seashells.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {165}, doi = {10.1038/d41586-018-05338-z}, pmid = {29895910}, issn = {1476-4687}, } @article {pmid29895909, year = {2018}, author = {}, title = {DNA offers glimmer of hope for critically endangered rhino.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {164}, doi = {10.1038/d41586-018-05335-2}, pmid = {29895909}, issn = {1476-4687}, } @article {pmid29895908, year = {2018}, author = {Maus, MV}, title = {Tumour tamed by transfer of one T cell.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {193-195}, doi = {10.1038/d41586-018-05251-5}, pmid = {29895908}, issn = {1476-4687}, mesh = {Humans ; Immunotherapy, Adoptive ; *Neoplasms ; *T-Lymphocytes ; }, } @article {pmid29895907, year = {2018}, author = {Goodrich, J and Taatjes, D}, title = {Transcription regulation enters a new phase.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {197-198}, doi = {10.1038/d41586-018-05244-4}, pmid = {29895907}, issn = {1476-4687}, support = {R01 GM068414/GM/NIGMS NIH HHS/United States ; }, mesh = {Biology ; Biophysical Phenomena ; *Biophysics ; Gene Expression Regulation ; *Molecular Biology ; }, } @article {pmid29895695, year = {2018}, author = {Terui, A and Ishiyama, N and Urabe, H and Ono, S and Finlay, JC and Nakamura, F}, title = {Metapopulation stability in branching river networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5963-E5969}, pmid = {29895695}, issn = {1091-6490}, mesh = {Animals ; *Ecosystem ; Fishes/*physiology ; *Models, Biological ; *Rivers ; }, abstract = {Intraspecific population diversity (specifically, spatial asynchrony of population dynamics) is an essential component of metapopulation stability and persistence in nature. In 2D systems, theory predicts that metapopulation stability should increase with ecosystem size (or habitat network size): Larger ecosystems will harbor more diverse subpopulations with more stable aggregate dynamics. However, current theories developed in simplified landscapes may be inadequate to predict emergent properties of branching ecosystems, an overlooked but widespread habitat geometry. Here, we combine theory and analyses of a unique long-term dataset to show that a scale-invariant characteristic of fractal river networks, branching complexity (measured as branching probability), stabilizes watershed metapopulations. In riverine systems, each branch (i.e., tributary) exhibits distinctive ecological dynamics, and confluences serve as "merging" points of those branches. Hence, increased levels of branching complexity should confer a greater likelihood of integrating asynchronous dynamics over the landscape. We theoretically revealed that the stabilizing effect of branching complexity is a consequence of purely probabilistic processes in natural conditions, where within-branch synchrony exceeds among-branch synchrony. Contrary to current theories developed in 2D systems, metapopulation size (a variable closely related to ecosystem size) had vague effects on metapopulation stability. These theoretical predictions were supported by 18-y observations of fish populations across 31 watersheds: Our cross-watershed comparisons revealed consistent stabilizing effects of branching complexity on metapopulations of very different riverine fishes. A strong association between branching complexity and metapopulation stability is likely to be a pervasive feature of branching networks that strongly affects species persistence during rapid environmental changes.}, } @article {pmid29895694, year = {2018}, author = {Iranzo, J and Martincorena, I and Koonin, EV}, title = {Cancer-mutation network and the number and specificity of driver mutations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6010-E6019}, pmid = {29895694}, issn = {1091-6490}, mesh = {*Gene Regulatory Networks ; *Genes, Neoplasm ; Humans ; *Models, Genetic ; *Mutation ; Neoplasms/*genetics/metabolism ; }, abstract = {Cancer genomics has produced extensive information on cancer-associated genes, but the number and specificity of cancer-driver mutations remains a matter of debate. We constructed a bipartite network in which 7,665 tumors from 30 cancer types are connected via shared mutations in 198 previously identified cancer genes. We show that about 27% of the tumors can be assigned to statistically supported modules, most of which encompass one or two cancer types. The rest of the tumors belong to a diffuse network component suggesting lower gene specificity of driver mutations. Linear regression of the mutational loads in cancer genes was used to estimate the number of drivers required for the onset of different cancers. The mean number of drivers in known cancer genes is approximately two, with a range of one to five. Cancers that are associated with modules had more drivers than those from the diffuse network component, suggesting that unidentified and/or interchangeable drivers exist in the latter.}, } @article {pmid29895693, year = {2018}, author = {Correia, MP and Stojanovic, A and Bauer, K and Juraeva, D and Tykocinski, LO and Lorenz, HM and Brors, B and Cerwenka, A}, title = {Distinct human circulating NKp30+FcεRIγ+CD8+ T cell population exhibiting high natural killer-like antitumor potential.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5980-E5989}, pmid = {29895693}, issn = {1091-6490}, mesh = {CD8-Positive T-Lymphocytes/*immunology/pathology ; Cell Line, Tumor ; Female ; HEK293 Cells ; Humans ; *Immunity, Cellular ; Killer Cells, Natural/*immunology/pathology ; Male ; Natural Cytotoxicity Triggering Receptor 3/*immunology ; Neoplasms/*immunology/pathology ; Receptors, Fc/*immunology ; }, abstract = {CD8+ T cells are considered prototypical cells of adaptive immunity. Here, we uncovered a distinct CD8+ T cell population expressing the activating natural killer (NK) receptor NKp30 in the peripheral blood of healthy individuals. We revealed that IL-15 could de novo induce NKp30 expression in a population of CD8+ T cells and drive their differentiation toward a broad innate transcriptional landscape. The adaptor FcεRIγ was concomitantly induced and was shown to be crucial to enable NKp30 cell-surface expression and function in CD8+ T cells. FcεRIγ de novo expression required promoter demethylation and was accompanied by acquisition of the signaling molecule Syk and the "innate" transcription factor PLZF. IL-15-induced NKp30+CD8+ T cells exhibited high NK-like antitumor activity in vitro and were able to synergize with T cell receptor signaling. Importantly, this population potently controlled tumor growth in a preclinical xenograft mouse model. Our study, while blurring the borders between innate and adaptive immunity, reveals a unique NKp30+FcεRIγ+CD8+ T cell population with high antitumor therapeutic potential.}, } @article {pmid29895692, year = {2018}, author = {Scaiewicz, A and Levitt, M}, title = {Unique function words characterize genomic proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6703-6708}, pmid = {29895692}, issn = {1091-6490}, support = {R35 GM122543/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Amino Acid Sequence ; Cluster Analysis ; *Conserved Sequence ; Databases, Factual ; *Genomics ; Humans ; *Protein Domains ; Sequence Alignment ; Sequence Homology, Amino Acid ; *Software ; Structure-Activity Relationship ; }, abstract = {Between 2009 and 2016 the number of protein sequences from known species increased 10-fold from 8 million to 85 million. About 80% of these sequences contain at least one region recognized by the conserved domain architecture retrieval tool (CDART) as a sequence motif. Motifs provide clues to biological function but CDART often matches the same region of a protein by two or more profiles. Such synonyms complicate estimates of functional complexity. We do full-linkage clustering of redundant profiles by finding maximum disjoint cliques: Each cluster is replaced by a single representative profile to give what we term a unique function word (UFW). From 2009 to 2016, the number of sequence profiles used by CDART increased by 80%; the number of UFWs increased more slowly by 30%, indicating that the number of UFWs may be saturating. The number of sequences matched by a single UFW (sequences with single domain architectures) increased as slowly as the number of different words, whereas the number of sequences matched by a combination of two or more UFWs in sequences with multiple domain architectures (MDAs) increased at the same rate as the total number of sequences. This combinatorial arrangement of a limited number of UFWs in MDAs accounts for the genomic diversity of protein sequences. Although eukaryotes and prokaryotes use very similar sets of "words" or UFWs (57% shared), the "sentences" (MDAs) are different (1.3% shared).}, } @article {pmid29895691, year = {2018}, author = {McKenzie, BA and Mamik, MK and Saito, LB and Boghozian, R and Monaco, MC and Major, EO and Lu, JQ and Branton, WG and Power, C}, title = {Caspase-1 inhibition prevents glial inflammasome activation and pyroptosis in models of multiple sclerosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6065-E6074}, pmid = {29895691}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Caspase 1/*metabolism ; Caspase Inhibitors/*pharmacology ; Cells, Cultured ; Dipeptides/*pharmacology ; Humans ; *Models, Biological ; Multiple Sclerosis/*enzymology/pathology ; Oligodendroglia/*enzymology/pathology ; Pyroptosis/*drug effects ; para-Aminobenzoates/*pharmacology ; }, abstract = {Multiple sclerosis (MS) is a progressive inflammatory demyelinating disease of the CNS of unknown cause that remains incurable. Inflammasome-associated caspases mediate the maturation and release of the proinflammatory cytokines IL-1β and IL-18 and activate the pore-forming protein gasdermin D (GSDMD). Inflammatory programmed cell death, pyroptosis, was recently shown to be mediated by GSDMD. Here, we report molecular evidence for GSDMD-mediated inflammasome activation and pyroptosis in both myeloid cells (macrophages/microglia) and, unexpectedly, in myelin-forming oligodendrocytes (ODCs) in the CNS of patients with MS and in the MS animal model, experimental autoimmune encephalomyelitis (EAE). We observed inflammasome activation and pyroptosis in human microglia and ODCs in vitro after exposure to inflammatory stimuli and demonstrate caspase-1 inhibition by the small-molecule inhibitor VX-765 in both cell types. GSDMD inhibition by siRNA transduction suppressed pyroptosis in human microglia. VX-765 treatment of EAE animals reduced the expression of inflammasome- and pyroptosis-associated proteins in the CNS, prevented axonal injury, and improved neurobehavioral performance. Thus, GSDMD-mediated pyroptosis in select glia cells is a previously unrecognized mechanism of inflammatory demyelination and represents a unique therapeutic opportunity for mitigating the disease process in MS and other CNS inflammatory diseases.}, } @article {pmid29895690, year = {2018}, author = {Yang, X and Meisl, G and Frohm, B and Thulin, E and Knowles, TPJ and Linse, S}, title = {On the role of sidechain size and charge in the aggregation of Aβ42 with familial mutations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5849-E5858}, pmid = {29895690}, issn = {1091-6490}, mesh = {Alzheimer Disease/*genetics/metabolism ; Amino Acid Substitution ; Amyloid beta-Peptides/*chemistry/*genetics/metabolism ; Humans ; *Mutation, Missense ; Peptide Fragments/*chemistry/*genetics/metabolism ; Protein Aggregation, Pathological/*genetics/metabolism ; }, abstract = {The aggregation of the amyloid-β (Aβ) peptide is linked to the pathogenesis of Alzheimer's disease (AD). In particular, some point mutations within Aβ are associated with early-onset familial Alzheimer's disease. Here we set out to explore how the physical properties of the altered side chains, including their sizes and charges, affect the molecular mechanisms of aggregation. We focus on Aβ42 with familial mutations-A21G (Flemish), E22K (Italian), E22G (Arctic), E22Q (Dutch), and D23N (Iowa)-which lead to similar or identical pathology with sporadic AD or severe cerebral amyloid angiopathy. Through global kinetic analysis, we find that for the E22K, E22G, E22Q, and D23N mutations, the acceleration of the overall aggregation originates primarily from the modulation of the nucleation processes, in particular secondary nucleation on the surface of existing fibrils, whereas the elongation process is not significantly affected. Remarkably, the D23 position appears to be responsible for most of the charge effects during nucleation, while the size of the side chain at the E22 position plays a more significant role than its charge. Thus, we have developed a kinetic approach to determine the nature and the magnitude of the contribution of specific residues to the rate of individual steps of the aggregation reaction, through targeted mutations and variations in ionic strength. This strategy can help rationalize the effect of some disease-related mutations as well as yield insights into the mechanism of aggregation and the transition states of the wild-type protein.}, } @article {pmid29895689, year = {2018}, author = {Letten, AD and Dhami, MK and Ke, PJ and Fukami, T}, title = {Species coexistence through simultaneous fluctuation-dependent mechanisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6745-6750}, pmid = {29895689}, issn = {1091-6490}, mesh = {Adaptation, Biological ; Amino Acids ; *Biodiversity ; Computer Simulation ; *Models, Biological ; Monte Carlo Method ; *Mycobiome ; Osmotic Pressure ; *Plant Nectar/chemistry ; Saccharomycetales/*physiology ; Species Specificity ; Sucrose ; }, abstract = {Understanding the origins and maintenance of biodiversity remains one of biology's grand challenges. From theory and observational evidence, we know that variability in environmental conditions through time is likely critical to the coexistence of competing species. Nevertheless, experimental tests of fluctuation-driven coexistence are rare and have typically focused on just one of two potential mechanisms, the temporal storage effect, to the neglect of the theoretically equally plausible mechanism known as relative nonlinearity of competition. We combined experiments and simulations in a system of nectar yeasts to quantify the relative contribution of the two mechanisms to coexistence. Resource competition models parameterized from single-species assays predicted the outcomes of mixed-culture competition experiments with 83% accuracy. Model simulations revealed that both mechanisms have measurable effects on coexistence and that relative nonlinearity can be equal or greater in magnitude to the temporal storage effect. In addition, we show that their effect on coexistence can be both antagonistic and complementary. These results falsify the common assumption that relative nonlinearity is of negligible importance, and in doing so reveal the importance of testing coexistence mechanisms in combination.}, } @article {pmid29895688, year = {2018}, author = {Fregel, R and Méndez, FL and Bokbot, Y and Martín-Socas, D and Camalich-Massieu, MD and Santana, J and Morales, J and Ávila-Arcos, MC and Underhill, PA and Shapiro, B and Wojcik, G and Rasmussen, M and Soares, AER and Kapp, J and Sockell, A and Rodríguez-Santos, FJ and Mikdad, A and Trujillo-Mederos, A and Bustamante, CD}, title = {Ancient genomes from North Africa evidence prehistoric migrations to the Maghreb from both the Levant and Europe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6774-6779}, pmid = {29895688}, issn = {1091-6490}, mesh = {Africa, Northern ; Agriculture/history ; Chromosomes, Human, Y/genetics ; DNA, Mitochondrial/genetics ; Ethnic Groups/*genetics/history ; Europe ; Gene Flow ; Gene Library ; Genetics, Population ; *Genome, Human ; History, Ancient ; Human Migration/*history ; Humans ; Middle East ; Morocco ; Sequence Analysis, DNA ; Spain/ethnology ; }, abstract = {The extent to which prehistoric migrations of farmers influenced the genetic pool of western North Africans remains unclear. Archaeological evidence suggests that the Neolithization process may have happened through the adoption of innovations by local Epipaleolithic communities or by demic diffusion from the Eastern Mediterranean shores or Iberia. Here, we present an analysis of individuals' genome sequences from Early and Late Neolithic sites in Morocco and from Early Neolithic individuals from southern Iberia. We show that Early Neolithic Moroccans (∼5,000 BCE) are similar to Later Stone Age individuals from the same region and possess an endemic element retained in present-day Maghrebi populations, confirming a long-term genetic continuity in the region. This scenario is consistent with Early Neolithic traditions in North Africa deriving from Epipaleolithic communities that adopted certain agricultural techniques from neighboring populations. Among Eurasian ancient populations, Early Neolithic Moroccans are distantly related to Levantine Natufian hunter-gatherers (∼9,000 BCE) and Pre-Pottery Neolithic farmers (∼6,500 BCE). Late Neolithic (∼3,000 BCE) Moroccans, in contrast, share an Iberian component, supporting theories of trans-Gibraltar gene flow and indicating that Neolithization of North Africa involved both the movement of ideas and people. Lastly, the southern Iberian Early Neolithic samples share the same genetic composition as the Cardial Mediterranean Neolithic culture that reached Iberia ∼5,500 BCE. The cultural and genetic similarities between Iberian and North African Neolithic traditions further reinforce the model of an Iberian migration into the Maghreb.}, } @article {pmid29895687, year = {2018}, author = {Soitu, C and Feuerborn, A and Tan, AN and Walker, H and Walsh, PA and Castrejón-Pita, AA and Cook, PR and Walsh, EJ}, title = {Microfluidic chambers using fluid walls for cell biology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5926-E5933}, pmid = {29895687}, issn = {1091-6490}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; MC_PC_15029//Medical Research Council/United Kingdom ; MR/K010867/1//Medical Research Council/United Kingdom ; }, mesh = {Cell Biology/instrumentation ; Cytological Techniques/instrumentation/methods ; *Lab-On-A-Chip Devices ; Microfluidic Analytical Techniques/*instrumentation/*methods ; }, abstract = {Many proofs of concept have demonstrated the potential of microfluidics in cell biology. However, the technology remains inaccessible to many biologists, as it often requires complex manufacturing facilities (such as soft lithography) and uses materials foreign to cell biology (such as polydimethylsiloxane). Here, we present a method for creating microfluidic environments by simply reshaping fluids on a substrate. For applications in cell biology, we use cell media on a virgin Petri dish overlaid with an immiscible fluorocarbon. A hydrophobic/fluorophilic stylus then reshapes the media into any pattern by creating liquid walls of fluorocarbon. Microfluidic arrangements suitable for cell culture are made in minutes using materials familiar to biologists. The versatility of the method is demonstrated by creating analogs of a common platform in cell biology, the microtiter plate. Using this vehicle, we demonstrate many manipulations required for cell culture and downstream analysis, including feeding, replating, cloning, cryopreservation, lysis plus RT-PCR, transfection plus genome editing, and fixation plus immunolabeling (when fluid walls are reconfigured during use). We also show that mammalian cells grow and respond to stimuli normally, and worm eggs develop into adults. This simple approach provides biologists with an entrée into microfluidics.}, } @article {pmid29895686, year = {2018}, author = {Mora-García, S and Yanovsky, MJ}, title = {A large deletion within the clock gene LNK2 contributed to the spread of tomato cultivation from Central America to Europe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6888-6890}, pmid = {29895686}, issn = {1091-6490}, mesh = {Arabidopsis ; *Arabidopsis Proteins ; Central America ; Europe ; *Lycopersicon esculentum ; Trans-Activators ; }, } @article {pmid29895685, year = {2018}, author = {Nguyen, TD and Qiao, B and Olvera de la Cruz, M}, title = {Efficient encapsulation of proteins with random copolymers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6578-6583}, pmid = {29895685}, issn = {1091-6490}, mesh = {Adsorption ; Bacterial Proteins/chemistry ; Carboxylic Ester Hydrolases/chemistry ; *Computer Simulation ; Drug Compounding/*methods ; Drug Design ; Fungal Proteins/chemistry ; Hydrophobic and Hydrophilic Interactions ; Lipase/chemistry ; *Models, Chemical ; Models, Molecular ; Organic Chemicals ; Pancreatic Elastase/chemistry ; Polymers/*chemistry ; Protein Conformation ; Proteins/*chemistry ; Solubility ; Solvents ; Subtilisin/chemistry ; Ubiquitin/chemistry ; }, abstract = {Membraneless organelles are aggregates of disordered proteins that form spontaneously to promote specific cellular functions in vivo. The possibility of synthesizing membraneless organelles out of cells will therefore enable fabrication of protein-based materials with functions inherent to biological matter. Since random copolymers contain various compositions and sequences of solvophobic and solvophilic groups, they are expected to function in nonbiological media similarly to a set of disordered proteins in membraneless organelles. Interestingly, the internal environment of these organelles has been noted to behave more like an organic solvent than like water. Therefore, an adsorbed layer of random copolymers that mimics the function of disordered proteins could, in principle, protect and enhance the proteins' enzymatic activity even in organic solvents, which are ideal when the products and/or the reactants have limited solubility in aqueous media. Here, we demonstrate via multiscale simulations that random copolymers efficiently incorporate proteins into different solvents with the potential to optimize their enzymatic activity. We investigate the key factors that govern the ability of random copolymers to encapsulate proteins, including the adsorption energy, copolymer average composition, and solvent selectivity. The adsorbed polymer chains have remarkably similar sequences, indicating that the proteins are able to select certain sequences that best reduce their exposure to the solvent. We also find that the protein surface coverage decreases when the fluctuation in the average distance between the protein adsorption sites increases. The results herein set the stage for computational design of random copolymers for stabilizing and delivering proteins across multiple media.}, } @article {pmid29895645, year = {2018}, author = {Beans, C}, title = {Inner Workings: Microscopy lights up stem cells in action.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6099-6101}, pmid = {29895645}, issn = {1091-6490}, mesh = {Animals ; Hair Follicle/cytology/diagnostic imaging ; Mice ; Microscopy, Fluorescence/*methods ; Optical Imaging/*methods ; Stem Cells/chemistry/*cytology/metabolism ; }, } @article {pmid29895428, year = {2018}, author = {Porter, CK and Akcali, CK}, title = {An Alternative to Adaptation by Sexual Selection: Habitat Choice.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {576-581}, doi = {10.1016/j.tree.2018.05.004}, pmid = {29895428}, issn = {1872-8383}, abstract = {Adaptation in mating signals and preferences has generally been explained by sexual selection. We propose that adaptation in such mating traits might also arise via a non-mutually exclusive process wherein individuals preferentially disperse to habitats where they experience high mating performance. Here we explore the evolutionary implications of this process.}, } @article {pmid29895411, year = {2018}, author = {Ferry-Danini, J}, title = {Should phenomenological approaches to illness be wary of naturalism?.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.shpsc.2018.05.006}, pmid = {29895411}, issn = {1879-2499}, abstract = {In some quarters within philosophy of medicine, more particularly in the phenomenological approaches, naturalism is looked upon with suspicion. This paper argues, first, that it is necessary to distinguish between two expressions of this attitude towards naturalism: phenomenological approaches to illness disagree with naturalism regarding various theoretical claims and they disapprove of naturalism on an ethical level. Second, this paper argues that both the disagreement with and the disapproval of naturalism are to a large extent confused. It then offers some proposals to set up an agenda for future collaboration.}, } @article {pmid29895329, year = {2018}, author = {Ovesen, C and Jakobsen, JC and Gluud, C and Steiner, T and Law, Z and Flaherty, K and Dineen, RA and Bath, PM and Sprigg, N and Christensen, H}, title = {Prevention of haematoma progression by tranexamic acid in intracerebral haemorrhage patients with and without spot sign on admission scan: a statistical analysis plan of a pre-specified sub-study of the TICH-2 trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {379}, pmid = {29895329}, issn = {1756-0500}, support = {project number 11_129_109//National Institute for Health Research/ ; grant no. 00012779//Velux Fonden/ ; }, mesh = {Antifibrinolytic Agents/administration & dosage/*pharmacology ; Cerebral Hemorrhage/*diagnostic imaging/*drug therapy ; *Data Interpretation, Statistical ; Disease Progression ; Hematoma/*diagnostic imaging/*drug therapy ; Humans ; Outcome Assessment (Health Care)/*statistics & numerical data ; Tranexamic Acid/administration & dosage/*pharmacology ; }, abstract = {OBJECTIVE: We present the statistical analysis plan of a prespecified Tranexamic Acid for Hyperacute Primary Intracerebral Haemorrhage (TICH)-2 sub-study aiming to investigate, if tranexamic acid has a different effect in intracerebral haemorrhage patients with the spot sign on admission compared to spot sign negative patients. The TICH-2 trial recruited above 2000 participants with intracerebral haemorrhage arriving in hospital within 8 h after symptom onset. They were included irrespective of radiological signs of on-going haematoma expansion. Participants were randomised to tranexamic acid versus matching placebo. In this subgroup analysis, we will include all participants in TICH-2 with a computed tomography angiography on admission allowing adjudication of the participants' spot sign status.

RESULTS: Primary outcome will be the ability of tranexamic acid to limit absolute haematoma volume on computed tomography at 24 h (± 12 h) after randomisation among spot sign positive and spot sign negative participants, respectively. Within all outcome measures, the effect of tranexamic acid in spot sign positive/negative participants will be compared using tests of interaction. This sub-study will investigate the important clinical hypothesis that spot sign positive patients might benefit more from administration of tranexamic acid compared to spot sign negative patients. Trial registration ISRCTN93732214 (http://www.isrctn.com).}, } @article {pmid29895328, year = {2018}, author = {Britto, FA and Cortade, F and Belloum, Y and Blaquière, M and Gallot, YS and Docquier, A and Pagano, AF and Jublanc, E and Bendridi, N and Koechlin-Ramonatxo, C and Chabi, B and Francaux, M and Casas, F and Freyssenet, D and Rieusset, J and Giorgetti-Peraldi, S and Carnac, G and Ollendorff, V and Favier, FB}, title = {Glucocorticoid-dependent REDD1 expression reduces muscle metabolism to enable adaptation under energetic stress.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {65}, pmid = {29895328}, issn = {1741-7007}, abstract = {BACKGROUND: Skeletal muscle atrophy is a common feature of numerous chronic pathologies and is correlated with patient mortality. The REDD1 protein is currently recognized as a negative regulator of muscle mass through inhibition of the Akt/mTORC1 signaling pathway. REDD1 expression is notably induced following glucocorticoid secretion, which is a component of energy stress responses.

RESULTS: Unexpectedly, we show here that REDD1 instead limits muscle loss during energetic stresses such as hypoxia and fasting by reducing glycogen depletion and AMPK activation. Indeed, we demonstrate that REDD1 is required to decrease O2 and ATP consumption in skeletal muscle via reduction of the extent of mitochondrial-associated endoplasmic reticulum membranes (MAMs), a central hub connecting energy production by mitochondria and anabolic processes. In fact, REDD1 inhibits ATP-demanding processes such as glycogen storage and protein synthesis through disruption of the Akt/Hexokinase II and PRAS40/mTORC1 signaling pathways in MAMs. Our results uncover a new REDD1-dependent mechanism coupling mitochondrial respiration and anabolic processes during hypoxia, fasting, and exercise.

CONCLUSIONS: Therefore, REDD1 is a crucial negative regulator of energy expenditure that is necessary for muscle adaptation during energetic stresses. This present study could shed new light on the role of REDD1 in several pathologies associated with energetic metabolism alteration, such as cancer, diabetes, and Parkinson's disease.}, } @article {pmid29895325, year = {2018}, author = {Sumi, A}, title = {Role of temperature in reported chickenpox cases in northern European countries: Denmark and Finland.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {377}, pmid = {29895325}, issn = {1756-0500}, support = {JP16K09061//JSPS KAKENHI/ ; JP25460769//JSPS KAKENHI/ ; }, mesh = {Chickenpox/*epidemiology ; Denmark/epidemiology ; Finland/epidemiology ; Humans ; *Seasons ; *Temperature ; }, abstract = {OBJECTIVE: In this study, we sought to explore the temperature-dependent transition of patterns of reported chickenpox cases in the northern European countries of Denmark and Finland to help determine the potential relationship with epidemiological factors of the disease. We performed time-series analysis consisting of a spectral analysis based on the maximum entropy method in the frequency domain and the nonlinear least squares method in the time domain, using the following time-series data: monthly data of reported chickenpox cases and mean temperatures in the pre-vaccination era for Denmark and Finland. The results were compared with those reported for China and Japan in our previous studies.

RESULTS: Time-series data of chickenpox cases for both Denmark and Finland showed a peak each winter, resulting in a unimodal cycle. For investigating the origin of the unimodal cycle, we set the contribution ratio of the 1-year cycle, Q1, as the contribution of the amplitude of a 1-year cycle, to the entire amplitude of the time-series data. The Q1 values for both countries clearly showed a positive correlation with the annual mean temperature of each country. The mean temperature substantially influenced the incidence of chickenpox in both countries.}, } @article {pmid29895323, year = {2018}, author = {Aquilina, B and Cauchi, RJ}, title = {Genetic screen identifies a requirement for SMN in mRNA localisation within the Drosophila oocyte.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {378}, pmid = {29895323}, issn = {1756-0500}, mesh = {Animals ; Drosophila Proteins/*genetics ; Drosophila melanogaster ; Genome, Insect/*genetics ; Oocytes/*metabolism ; RNA, Messenger/*genetics ; RNA-Binding Proteins/*genetics ; Transforming Growth Factor alpha/genetics ; }, abstract = {OBJECTIVE: Spinal muscular atrophy (SMA) results from insufficient levels of the survival motor neuron (SMN) protein. Drosophila is conducive to large-scale genetic-modifier screens which can reveal novel pathways underpinning the disease mechanism. We tested the ability of a large collection of genomic deletions to enhance SMN-dependent lethality. To test our design, we asked whether our study can identify loci containing genes identified in previous genetic screens. Our objective was to find a common link between genes flagged in independent screens, which would allow us to expose novel functions for SMN in vivo.

RESULTS: Out of 128 chromosome deficiency lines, 12 (9.4%) were found to consistently depress adult viability when crossed to SMN loss-of-function heterozygotes. In their majority, the enhancing deletions harboured genes that were previously identified as genetic modifiers, hence, validating the design of the screen. Importantly, gene overlap allowed us to flag genes with a role in post-transcriptional regulation of mRNAs that are crucial for determining the axes of the oocyte and future embryo. We find that SMN is also required for the correct localisation of gurken and oskar mRNAs in oocytes. These findings extend the role of SMN in oogenesis by identifying a key requirement for mRNA trafficking.}, } @article {pmid29895315, year = {2018}, author = {Mariye, T and Tasew, H and Teklay, G and Gerensea, H and Daba, W}, title = {Magnitude of diabetes self-care practice and associated factors among type two adult diabetic patients following at public Hospitals in central zone, Tigray Region, Ethiopia, 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {380}, pmid = {29895315}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/epidemiology/*therapy ; Ethiopia/epidemiology ; Female ; *Health Knowledge, Attitudes, Practice ; Hospitals, Public/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Self Care/*statistics & numerical data ; }, abstract = {OBJECTIVE: Self-care practice in type two diabetes is a critical factor to keep the disease under control. Despite the important role of self-care practices in management of diabetes were recognized to be useful and effective in achieving diabetes control and preventing its complication, findings of previous studies in Ethiopia were confirmed that, aspects of self-care practices were more problematic. So that this study focus on magnitude of self-care practice and associated factors among diabetic patients.

RESULTS: Among the total 284 respondents, their mean age was 52.19 years and about 178 (62.7%) had poor diabetic self-care practice. Having glucometer at home (AOR = 3. 719 [1.700, 8.139]), knowing fasting glucose level (AOR = 2. 709 [1.481, 4.957]), attending diabetic education (AOR = 2. 487 [2.027, 6.020]), perceived benefit (AOR = 2. 422 [1.374, 4.269]), perceived barrier (AOR = 0. 471 [0.265, 0.394]), and self-employment (AOR = 5. 936 [1.965, 17.936]) were significantly associated with good self-care practice.}, } @article {pmid29895260, year = {2018}, author = {Du, X and Liu, S and Sun, J and Zhang, G and Jia, Y and Pan, Z and Xiang, H and He, S and Xia, Q and Xiao, S and Shi, W and Quan, Z and Liu, J and Ma, J and Pang, B and Wang, L and Sun, G and Gong, W and Jenkins, JN and Lou, X and Zhu, J and Xu, H}, title = {Dissection of complicate genetic architecture and breeding perspective of cottonseed traits by genome-wide association study.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {451}, pmid = {29895260}, issn = {1471-2164}, support = {2016YFD0100203//the National Key Research and Development Program of China/ ; 31671570 and 31470083//The National Natural Science Foundation of China/ ; }, mesh = {Fatty Acids/analysis ; Genes, Plant ; Genome-Wide Association Study ; Genotype ; Gossypium/chemistry/*genetics ; Plant Breeding ; Plant Proteins/genetics ; Quantitative Trait, Heritable ; Seeds/chemistry/*genetics ; }, abstract = {BACKGROUND: Cottonseed is one of the most important raw materials for plant protein, oil and alternative biofuel for diesel engines. Understanding the complex genetic basis of cottonseed traits is requisite for achieving efficient genetic improvement of the traits. However, it is not yet clear about their genetic architecture in genomic level. GWAS has been an effective way to explore genetic basis of quantitative traits in human and many crops. This study aims to dissect genetic mechanism seven cottonseed traits by a GWAS for genetic improvement.

RESULTS: A genome-wide association study (GWAS) based on a full gene model with gene effects as fixed and gene-environment interaction as random, was conducted for protein, oil and 5 fatty acids using 316 accessions and ~ 390 K SNPs. Totally, 124 significant quantitative trait SNPs (QTSs), consisting of 16, 21, 87 for protein, oil and fatty acids (palmitic, linoleic, oleic, myristic, stearic), respectively, were identified and the broad-sense heritability was estimated from 71.62 to 93.43%; no QTS-environment interaction was detected for the protein, the palmitic and the oleic contents; the protein content was predominantly controlled by epistatic effects accounting for 65.18% of the total variation, but the oil content and the fatty acids except the palmitic were mainly determined by gene main effects and no epistasis was detected for the myristic and the stearic. Prediction of superior pure line and hybrid revealed the potential of the QTSs in the improvement of cottonseed traits, and the hybrid could achieve higher or lower genetic values compared with pure lines.

CONCLUSIONS: This study revealed complex genetic architecture of seven cottonseed traits at whole genome-wide by mixed linear model approach; the identified genetic variants and estimated genetic component effects of gene, gene-gene and gene-environment interaction provide cotton geneticist or breeders new knowledge on the genetic mechanism of the traits and the potential molecular breeding design strategy.}, } @article {pmid29895016, year = {2018}, author = {Hadziselimovic, F}, title = {Commentary on the Article "Androgen Insensitivity Syndrome at Prepuberty: Marked Loss of Spermatogonial Cells at Early Childhood and Presence of Gonocytes up to Puberty" by Aliberti et al.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {4}, pages = {161-162}, doi = {10.1159/000490212}, pmid = {29895016}, issn = {1661-5433}, mesh = {*Androgen-Insensitivity Syndrome ; Child, Preschool ; Humans ; Male ; Puberty ; Receptors, Androgen ; *Sexual Maturation ; Spermatogonia ; }, } @article {pmid29894995, year = {2018}, author = {Navarrete, AF and Blezer, ELA and Pagnotta, M and de Viet, ESM and Todorov, OS and Lindenfors, P and Laland, KN and Reader, SM}, title = {Primate Brain Anatomy: New Volumetric MRI Measurements for Neuroanatomical Studies.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {2}, pages = {109-117}, doi = {10.1159/000488136}, pmid = {29894995}, issn = {1421-9743}, abstract = {Since the publication of the primate brain volumetric dataset of Stephan and colleagues in the early 1980s, no major new comparative datasets covering multiple brain regions and a large number of primate species have become available. However, technological and other advances in the last two decades, particularly magnetic resonance imaging (MRI) and the creation of institutions devoted to the collection and preservation of rare brain specimens, provide opportunities to rectify this situation. Here, we present a new dataset including brain region volumetric measurements of 39 species, including 20 species not previously available in the literature, with measurements of 16 brain areas. These volumes were extracted from MRI of 46 brains of 38 species from the Netherlands Institute of Neuroscience Primate Brain Bank, scanned at high resolution with a 9.4-T scanner, plus a further 7 donated MRI of 4 primate species. Partial measurements were made on an additional 8 brains of 5 species. We make the dataset and MRI scans available online in the hope that they will be of value to researchers conducting comparative studies of primate evolution.}, } @article {pmid29894731, year = {2018}, author = {Hutter, CR and Lambert, SM and Andriampenomanana, ZF and Glaw, F and Vences, M}, title = {Molecular phylogeny and diversification of Malagasy bright-eyed tree frogs (Mantellidae: Boophis).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {568-578}, doi = {10.1016/j.ympev.2018.05.027}, pmid = {29894731}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification/genetics ; Bayes Theorem ; Biodiversity ; Biological Evolution ; Madagascar ; Phylogeny ; }, abstract = {We investigate the molecular phylogeny of Boophis, a group of arboreal frogs from the Malagasy-Comoroan family Mantellidae. Based on newly acquired DNA sequences of five mitochondrial and five nuclear markers (7444 base pairs), we infer a phylogeny of Boophis with complete species-level taxon sampling. We reconstruct the phylogeny using Bayesian inference and maximum likelihood and estimate divergence dates for the major clades of the genus. The phylogenetic analyses together support the monophyly of the two subgenera (Sahona and Boophis), and provide strong support for most previously identified species groups, except that the B. ulftunni group is nested within the B. majori group. We also erect a new species group related to the B. mandraka group, the B. blommersae group, composed of small-sized, brown stream-breeding frogs previously included within the B. majori group. Finally, we use the resulting phylogeny to illustrate striking examples of repeated evolution of coloration and ventral transparency and address the biogeographic history and broad pattern of species diversification in the genus. Ancestral area reconstructions provide evidence that Boophis diversified within the Eastern highland forests of Madagascar, and we suggest that adaptation to these highland areas was important in their diversification.}, } @article {pmid29893954, year = {2018}, author = {Tamura, K and Tao, Q and Kumar, S}, title = {Theoretical Foundation of the RelTime Method for Estimating Divergence Times from Variable Evolutionary Rates.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1770-1782}, pmid = {29893954}, issn = {1537-1719}, support = {R01 GM126567/GM/NIGMS NIH HHS/United States ; }, abstract = {RelTime estimates divergence times by relaxing the assumption of a strict molecular clock in a phylogeny. It shows excellent performance in estimating divergence times for both simulated and empirical molecular sequence data sets in which evolutionary rates varied extensively throughout the tree. RelTime is computationally efficient and scales well with increasing size of data sets. Until now, however, RelTime has not had a formal mathematical foundation. Here, we show that the basis of the RelTime approach is a relative rate framework (RRF) that combines comparisons of evolutionary rates in sister lineages with the principle of minimum rate change between evolutionary lineages and their respective descendants. We present analytical solutions for estimating relative lineage rates and divergence times under RRF. We also discuss the relationship of RRF with other approaches, including the Bayesian framework. We conclude that RelTime will be useful for phylogenies with branch lengths derived not only from molecular data, but also morphological and biochemical traits.}, } @article {pmid29893912, year = {2018}, author = {Ralf, A and González, DM and Zhong, K and Kayser, M}, title = {Yleaf: Software for Human Y-Chromosomal Haplogroup Inference from Next-Generation Sequencing Data.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1820}, doi = {10.1093/molbev/msy080}, pmid = {29893912}, issn = {1537-1719}, } @article {pmid29893911, year = {2018}, author = {Velová, H and Gutowska-Ding, MW and Burt, DW and Vinkler, M}, title = {Toll-like receptor evolution in birds: gene duplication, pseudogenisation and diversifying selection.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29893911}, issn = {1537-1719}, abstract = {Toll-like receptors (TLRs) are key sensor molecules in vertebrates triggering initial phases of immune responses to pathogens. The avian TLR family typically consists of ten receptors, each adapted to distinct ligands. To understand the complex evolutionary history of each avian TLR, we analysed all members of the TLR family in the whole genome assemblies and target sequence data of 63 bird species covering all major avian clades. Our results indicate that gene duplication events most probably occurred in TLR1 before synapsids diversified from sauropsids. Unlike mammals, ssRNA-recognising TLR7 has duplicated independently in several avian taxa, while flagellin-sensing TLR5 has pseudogenised multiple times in bird phylogeny. Our analysis revealed stronger positive, diversifying selection acting in TLR5 and the three-domain TLRs (TLR10 [TLR1A], TLR1 [TLR1B], TLR2A, TLR2B, TLR4) that face the extracellular space and bind complex ligands than in single-domain TLR15 and endosomal TLRs (TLR3, TLR7, TLR21). In total, 84 out of 306 positively selected sites were predicted to harbour substitutions dramatically changing the amino acid physicochemical properties. Furthermore, 105 positively selected sites were located in the known functionally-relevant TLR regions. We found evidence for convergent evolution acting between birds and mammals at 54 of these sites. Our comparative study provides a comprehensive insight into the evolution of avian TLR genetic variability. Besides describing the history of avian TLR gene gain and gene loss, we also identified candidate positions in the receptors that have been likely shaped by direct molecular host-pathogen co-evolutionary interactions and most probably play key functional roles in birds.}, } @article {pmid29893904, year = {2018}, author = {Stanek, G and Strle, F}, title = {Lyme borreliosis-from tick bite to diagnosis and treatment.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {233-258}, doi = {10.1093/femsre/fux047}, pmid = {29893904}, issn = {1574-6976}, mesh = {Animals ; Anti-Bacterial Agents/*administration & dosage ; Borrelia burgdorferi/physiology ; Humans ; Lyme Disease/*diagnosis/*drug therapy/microbiology/transmission ; *Tick Bites ; Treatment Outcome ; }, abstract = {Lyme borreliosis is caused by certain genospecies of the Borrelia burgdorferi sensu lato complex, which are transmitted by hard ticks of the genus Ixodes. The most common clinical manifestation is erythema migrans, an expanding skin redness that usually develops at the site of a tick bite and eventually resolves even without antibiotic treatment. The infecting pathogens can spread to other tissues and organs, resulting in manifestations that can involve the nervous system, joints, heart and skin. Fatal outcome is extremely rare and is due to severe heart involvement; fetal involvement is not reliably ascertained. Laboratory support-mainly by serology-is essential for diagnosis, except in the case of typical erythema migrans. Treatment is usually with antibiotics for 2 to 4 weeks; most patients recover uneventfully. There is no convincing evidence for antibiotic treatment longer than 4 weeks and there is no reliable evidence for survival of borreliae in adequately treated patients. European Lyme borreliosis is a frequent disease with increasing incidence. However, numerous scientifically questionable ideas on its clinical presentation, diagnosis and treatment may confuse physicians and lay people. Since diagnosis of Lyme borreliosis should be based on appropriate clinical signs, solid knowledge of clinical manifestations is essential.}, } @article {pmid29893875, year = {2018}, author = {Pierini, F and Lenz, TL}, title = {Divergent allele advantage at human MHC genes: signatures of past and ongoing selection.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29893875}, issn = {1537-1719}, abstract = {The highly polymorphic genes of the major histocompatibility complex (MHC) play a key role in adaptive immunity. Divergent allele advantage, a mechanism of balancing selection, is proposed to contribute to their exceptional polymorphism. It assumes that MHC genotypes with more divergent alleles allow for broader antigen-presentation to immune effector cells, by that increasing immunocompetence. However, the direct correlation between pairwise sequence divergence and the corresponding repertoire of bound peptides has not been studied systematically across different MHC genes. Here, we investigated this relationship for five key classical human MHC genes (human leukocyte antigen; HLA-A, -B, -C, -DRB1, and -DQB1), using allele-specific computational binding prediction to 118,097 peptides derived from a broad range of human pathogens. For all five human MHC genes, the genetic distance between two alleles of a heterozygous genotype was positively correlated with the total number of peptides bound by these two alleles. In accordance with the major antigen-presentation pathway of MHC class I molecules, HLA-B and HLA-C alleles showed particularly strong correlations for peptides derived from intracellular pathogens. Intriguingly, this bias coincides with distinct protein compositions between intra- and extracellular pathogens, possibly suggesting adaptation of MHC I molecules to present specifically intracellular peptides. Eventually, we observed significant positive correlations between an allele's average divergence and its population frequency. Overall, our results support the divergent allele advantage as a meaningful quantitative mechanism through which pathogen-mediated selection leads to the evolution of MHC diversity.}, } @article {pmid29893836, year = {2018}, author = {Purkamo, L and Kietäväinen, R and Miettinen, H and Sohlberg, E and Kukkonen, I and Itävaara, M and Bomberg, M}, title = {Diversity and functionality of archaeal, bacterial and fungal communities in deep Archaean bedrock groundwater.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy116}, pmid = {29893836}, issn = {1574-6941}, abstract = {The diversity and metabolic functions of deep subsurface ecosystems remain relatively unexplored. Microbial communities in previously studied deep subsurface sites of the Fennoscandian Shield are distinctive to each site. Thus, we hypothesized that the microbial communities of the deep Archaean bedrock fracture aquifer in Romuvaara, northern Finland, differ both in community composition and metabolic functionality from the other sites in the Fennoscandian Shield. We characterized the composition, functionality and substrate preferences of the microbial communities at different depths in a 600 m deep borehole. In contrast to other Fennoscandian deep biosphere communities studied to date, iron-oxidizing Gallionella dominated the bacterial communities, while methanogenic and ammonia-oxidizing archaea were the most prominent archaea, and a diverse fungal community was also detected. Potential for methane cycling and sulfate and nitrate reduction was confirmed by detection of the functional genes of these metabolic pathways. Organotrophs were less abundant, although carbohydrates were the most preferred of the tested substrates. The microbial communities shared features with those detected from other deep groundwaters with similar geochemistry, but the majority of taxa distinctive to Romuvaara are different from the taxa previously detected in saline deep groundwater in the Fennoscandian Shield, most likely because of the differences in water chemistry.}, } @article {pmid29893835, year = {2018}, author = {Lee, CJD and McMullan, PE and O'Kane, CJ and Stevenson, A and Santos, IC and Roy, C and Ghosh, W and Mancinelli, RL and Mormile, MR and McMullan, G and Banciu, HL and Fares, MA and Benison, KC and Oren, A and Dyall-Smith, ML and Hallsworth, JE}, title = {NaCl-saturated brines are thermodynamically moderate, rather than extreme, microbial habitats.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {672-693}, doi = {10.1093/femsre/fuy026}, pmid = {29893835}, issn = {1574-6976}, mesh = {Archaea/*physiology ; Bacteria ; *Bacterial Physiological Phenomena ; *Ecosystem ; Salts/*chemistry ; Sodium Chloride/*chemistry ; Thermodynamics ; *Water Microbiology ; }, abstract = {NaCl-saturated brines such as saltern crystalliser ponds, inland salt lakes, deep-sea brines and liquids-of-deliquescence on halite are commonly regarded as a paradigm for the limit of life on Earth. There are, however, other habitats that are thermodynamically more extreme. Typically, NaCl-saturated environments contain all domains of life and perform complete biogeochemical cycling. Despite their reduced water activity, ∼0.755 at 5 M NaCl, some halophiles belonging to the Archaea and Bacteria exhibit optimum growth/metabolism in these brines. Furthermore, the recognised water-activity limit for microbial function, ∼0.585 for some strains of fungi, lies far below 0.755. Other biophysical constraints on the microbial biosphere (temperatures of >121°C; pH > 12; and high chaotropicity; e.g. ethanol at >18.9% w/v (24% v/v) and MgCl2 at >3.03 M) can prevent any cellular metabolism or ecosystem function. By contrast, NaCl-saturated environments contain biomass-dense, metabolically diverse, highly active and complex microbial ecosystems; and this underscores their moderate character. Here, we survey the evidence that NaCl-saturated brines are biologically permissive, fertile habitats that are thermodynamically mid-range rather than extreme. Indeed, were NaCl sufficiently soluble, some halophiles might grow at concentrations of up to 8 M. It may be that the finite solubility of NaCl has stabilised the genetic composition of halophile populations and limited the action of natural selection in driving halophile evolution towards greater xerophilicity. Further implications are considered for the origin(s) of life and other aspects of astrobiology.}, } @article {pmid29893833, year = {2018}, author = {Delaye, L and Ruiz-Ruiz, S and Calderon, E and Tarazona, S and Conesa, A and Moya, A}, title = {Evidence of the Red-Queen Hypothesis from Accelerated Rates of Evolution of Genes Involved in Biotic Interactions in Pneumocystis.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1596-1606}, pmid = {29893833}, issn = {1759-6653}, mesh = {Biota/*genetics ; Evolution, Molecular ; Fungal Proteins/genetics ; Gene Expression Regulation, Fungal/genetics ; Membrane Glycoproteins/genetics ; Pneumocystis/*genetics ; Selection, Genetic/genetics ; }, abstract = {Pneumocystis species are ascomycete fungi adapted to live inside the lungs of mammals. These ascomycetes show extensive stenoxenism, meaning that each species of Pneumocystis infects a single species of host. Here, we study the effect exerted by natural selection on gene evolution in the genomes of three Pneumocystis species. We show that genes involved in host interaction evolve under positive selection. In the first place, we found strong evidence of episodic diversifying selection in Major surface glycoproteins (Msg). These proteins are located on the surface of Pneumocystis and are used for host attachment and probably for immune system evasion. Consistent with their function as antigens, most sites under diversifying selection in Msg code for residues with large relative surface accessibility areas. We also found evidence of positive selection in part of the cell machinery used to export Msg to the cell surface. Specifically, we found that genes participating in glycosylphosphatidylinositol (GPI) biosynthesis show an increased rate of nonsynonymous substitutions (dN) versus synonymous substitutions (dS). GPI is a molecule synthesized in the endoplasmic reticulum that is used to anchor proteins to membranes. We interpret the aforementioned findings as evidence of selective pressure exerted by the host immune system on Pneumocystis species, shaping the evolution of Msg and several proteins involved in GPI biosynthesis. We suggest that genome evolution in Pneumocystis is well described by the Red-Queen hypothesis whereby genes relevant for biotic interactions show accelerated rates of evolution.}, } @article {pmid29893825, year = {2018}, author = {Askarian, F and Wagner, T and Johannessen, M and Nizet, V}, title = {Staphylococcus aureus modulation of innate immune responses through Toll-like (TLR), (NOD)-like (NLR) and C-type lectin (CLR) receptors.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {656-671}, pmid = {29893825}, issn = {1574-6976}, support = {U01 AI124316/AI/NIAID NIH HHS/United States ; R01 HL125352/HL/NHLBI NIH HHS/United States ; }, mesh = {Immunity, Innate/*immunology ; Lectins, C-Type/*metabolism ; NLR Proteins/*metabolism ; Staphylococcus aureus/genetics/*immunology ; Toll-Like Receptors/*metabolism ; }, abstract = {Early recognition of pathogens by the innate immune system is crucial for bacterial clearance. Many pattern recognition receptors (PRRs) such as Toll-like (TLRs) and (NOD)-like (NLRs) receptors have been implicated in initial sensing of bacterial components. The intracellular signaling cascades triggered by these receptors result in transcriptional upregulation of inflammatory pathways. Although this step is crucial for bacterial elimination, it is also associated with the potential for substantial immunopathology, which underscores the need for tight control of inflammatory responses. The leading human bacterial pathogen Staphylococcus aureus expresses over 100 virulence factors that exert numerous effects upon host cells. In this manner, the pathogen seeks to avoid host recognition or perturb PRR-induced innate immune responses to allow optimal survival in the host. These immune system interactions may result in enhanced bacterial proliferation but also provoke systemic cytokine responses associated with sepsis. This review summarizes recent findings on the various mechanisms applied by S. aureus to modulate or interfere with inflammatory responses through PRRs. Detailed understanding of these complex interactions can provide new insights toward future immune-stimulatory therapeutics against infection or immunomodulatory therapeutics to suppress or correct dysregulated inflammation.}, } @article {pmid29893666, year = {2018}, author = {Kang, H and Cha, I and Kim, H and Joh, K}, title = {Maribacter maritimus sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2431-2436}, doi = {10.1099/ijsem.0.002843}, pmid = {29893666}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-negative, motile by gliding and straight rod-shaped bacterial strain, designated HMF3635T, was isolated from seawater of the East Sea, Republic of Korea. Strain HMF3635T grew optimally on marine agar at 30 °C, pH 7.0-8.0 and 2.0 % NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain HMF3635T belonged to the genus Maribacter and was most closely related to Maribacter arenosus CAU 1321T (96.4 % sequence similarity) and Maribacter polysiphoniae KMM 6151T (96.0 %). The major fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The only respiratory quinone was menaquinone 6. The major polar lipids were phosphatidylethanolamine, four unidentified aminolipids, one unidentified phospholipid and three unidentified polar lipids. The DNA G+C content was 38.7 mol%. On the basis of the evidence presented in this study, strain HMF3635T represents a novel species of the genus Maribacter, for which the name Maribacter maritimus sp. nov. is proposed. The type strain of the species is strain HMF3635T (=KCTC 52399T=NBRC 112671T).}, } @article {pmid29892335, year = {2018}, author = {Gomez, JP and Robinson, SK and Blackburn, JK and Ponciano, JM}, title = {An efficient extension of N-mixture models for multi-species abundance estimation.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {2}, pages = {340-353}, pmid = {29892335}, issn = {2041-210X}, support = {R01 GM117617/GM/NIGMS NIH HHS/United States ; }, abstract = {In this study we propose an extension of the N-mixture family of models that targets an improvement of the statistical properties of rare species abundance estimators when sample sizes are low, yet typical for tropical studies. The proposed method harnesses information from other species in an ecological community to correct each species' estimator. We provide guidance to determine the sample size required to estimate accurately the abundance of rare tropical species when attempting to estimate the abundance of single species.We evaluate the proposed methods using an assumption of 50 m radius plots and perform simulations comprising a broad range of sample sizes, true abundances and detectability values and a complex data generating process. The extension of the N-mixture model is achieved by assuming that the detection probabilities are drawn at random from a beta distribution in a multi-species fashion. This hierarchical model avoids having to specify a single detection probability parameter per species in the targeted community. Parameter estimation is done via Maximum Likelihood.We compared our multi-species approach with previously proposed multi-species N-mixture models, which we show are biased when the true densities of species in the community are less than seven individuals per 100 hectares. The beta N-mixture model proposed here outperforms the traditional Multi-species N-mixture model by allowing the estimation of organisms at lower densities and controlling the bias in the estimation.We illustrate how our methodology can be used to suggest sample sizes required to estimate the abundance of organisms, when these are either rare, common or abundant. When the interest is full communities, we show how the multi-species approaches, and in particular our beta model and estimation methodology, can be used as a practical solution to estimate organism densities from rapid inventory datasets. The statistical inferences done with our model via Maximum Likelihood can also be used to group species in a community according to their detectabilities.}, } @article {pmid29892059, year = {2018}, author = {Knopp, M and Andersson, DI}, title = {No beneficial fitness effects of random peptides.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1046-1047}, doi = {10.1038/s41559-018-0585-4}, pmid = {29892059}, issn = {2397-334X}, } @article {pmid29892058, year = {2018}, author = {Tautz, D and Neme, R}, title = {Reply to 'No beneficial fitness effects of random peptides'.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1048}, doi = {10.1038/s41559-018-0586-3}, pmid = {29892058}, issn = {2397-334X}, } @article {pmid29892031, year = {2018}, author = {Yao, B and Huang, SW and Liu, Y and Vinod, AK and Choi, C and Hoff, M and Li, Y and Yu, M and Feng, Z and Kwong, DL and Huang, Y and Rao, Y and Duan, X and Wong, CW}, title = {Gate-tunable frequency combs in graphene-nitride microresonators.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {410-414}, doi = {10.1038/s41586-018-0216-x}, pmid = {29892031}, issn = {1476-4687}, abstract = {Optical frequency combs, which emit pulses of light at discrete, equally spaced frequencies, are cornerstones of modern-day frequency metrology, precision spectroscopy, astronomical observations, ultrafast optics and quantum information1-7. Chip-scale frequency combs, based on the Kerr and Raman nonlinearities in monolithic microresonators with ultrahigh quality factors8-10, have recently led to progress in optical clockwork and observations of temporal cavity solitons11-14. But the chromatic dispersion within a laser cavity, which determines the comb formation15,16, is usually difficult to tune with an electric field, whether in microcavities or fibre cavities. Such electrically dynamic control could bridge optical frequency combs and optoelectronics, enabling diverse comb outputs in one resonator with fast and convenient tunability. Arising from its exceptional Fermi-Dirac tunability and ultrafast carrier mobility17-19, graphene has a complex optical dispersion determined by its optical conductivity, which can be tuned through a gate voltage20,21. This has brought about optoelectronic advances such as modulators22,23, photodetectors 24 and controllable plasmonics25,26. Here we demonstrate the gated intracavity tunability of graphene-based optical frequency combs, by coupling the gate-tunable optical conductivity to a silicon nitride photonic microresonator, thus modulating its second- and higher-order chromatic dispersions by altering the Fermi level. Preserving cavity quality factors up to 106 in the graphene-based comb, we implement a dual-layer ion-gel-gated transistor to tune the Fermi level of graphene across the range 0.45-0.65 electronvolts, under single-volt-level control. We use this to produce charge-tunable primary comb lines from 2.3 terahertz to 7.2 terahertz, coherent Kerr frequency combs, controllable Cherenkov radiation and controllable soliton states, all in a single microcavity. We further demonstrate voltage-tunable transitions from periodic soliton crystals to crystals with defects, mapped by our ultrafast second-harmonic optical autocorrelation. This heterogeneous graphene microcavity, which combines single-atomic-layer nanoscience and ultrafast optoelectronics, will help to improve our understanding of dynamical frequency combs and ultrafast optics.}, } @article {pmid29892026, year = {2018}, author = {Woolston, C}, title = {Why a new lab can be a valuable destination for postdocs and graduate students.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {333-335}, doi = {10.1038/d41586-018-05381-w}, pmid = {29892026}, issn = {1476-4687}, mesh = {*Education, Graduate ; Financing, Organized ; Freedom ; *Job Satisfaction ; *Laboratories/economics ; Mentoring/standards ; Research Personnel/*education/psychology ; *Students/psychology ; }, } @article {pmid29892025, year = {2018}, author = {Slangen, A}, title = {How humans and rising seas affect each other.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {196-197}, doi = {10.1038/d41586-018-05366-9}, pmid = {29892025}, issn = {1476-4687}, } @article {pmid29892024, year = {2018}, author = {Tachibana, CY}, title = {Stem-cell culture moves to the third dimension.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {329-331}, doi = {10.1038/d41586-018-05380-x}, pmid = {29892024}, issn = {1476-4687}, mesh = {Animals ; Cell Culture Techniques/*methods ; Humans ; Lab-On-A-Chip Devices/*trends ; Organoids/*cytology/metabolism ; Stem Cells/*cytology/metabolism ; }, } @article {pmid29892020, year = {2018}, author = {Burnham, PM and Hendrixson, DR}, title = {Campylobacter jejuni: collective components promoting a successful enteric lifestyle.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {551-565}, doi = {10.1038/s41579-018-0037-9}, pmid = {29892020}, issn = {1740-1534}, support = {R01 AI065539/AI/NIAID NIH HHS/United States ; }, abstract = {Campylobacter jejuni is the leading cause of bacterial diarrhoeal disease in many areas of the world. The high incidence of sporadic cases of disease in humans is largely due to its prevalence as a zoonotic agent in animals, both in agriculture and in the wild. Compared with many other enteric bacterial pathogens, C. jejuni has strict growth and nutritional requirements and lacks many virulence and colonization determinants that are typically used by bacterial pathogens to infect hosts. Instead, C. jejuni has a different collection of factors and pathways not typically associated together in enteric pathogens to establish commensalism in many animal hosts and to promote diarrhoeal disease in the human population. In this Review, we discuss the cellular architecture and structure of C. jejuni, intraspecies genotypic variation, the multiple roles of the flagellum, specific nutritional and environmental growth requirements and how these factors contribute to in vivo growth in human and avian hosts, persistent colonization and pathogenesis of diarrhoeal disease.}, } @article {pmid29892016, year = {2018}, author = {Schumacher, FR and Al Olama, AA and Berndt, SI and Benlloch, S and Ahmed, M and Saunders, EJ and Dadaev, T and Leongamornlert, D and Anokian, E and Cieza-Borrella, C and Goh, C and Brook, MN and Sheng, X and Fachal, L and Dennis, J and Tyrer, J and Muir, K and Lophatananon, A and Stevens, VL and Gapstur, SM and Carter, BD and Tangen, CM and Goodman, PJ and Thompson, IM and Batra, J and Chambers, S and Moya, L and Clements, J and Horvath, L and Tilley, W and Risbridger, GP and Gronberg, H and Aly, M and Nordström, T and Pharoah, P and Pashayan, N and Schleutker, J and Tammela, TLJ and Sipeky, C and Auvinen, A and Albanes, D and Weinstein, S and Wolk, A and Håkansson, N and West, CML and Dunning, AM and Burnet, N and Mucci, LA and Giovannucci, E and Andriole, GL and Cussenot, O and Cancel-Tassin, G and Koutros, S and Beane Freeman, LE and Sorensen, KD and Orntoft, TF and Borre, M and Maehle, L and Grindedal, EM and Neal, DE and Donovan, JL and Hamdy, FC and Martin, RM and Travis, RC and Key, TJ and Hamilton, RJ and Fleshner, NE and Finelli, A and Ingles, SA and Stern, MC and Rosenstein, BS and Kerns, SL and Ostrer, H and Lu, YJ and Zhang, HW and Feng, N and Mao, X and Guo, X and Wang, G and Sun, Z and Giles, GG and Southey, MC and MacInnis, RJ and FitzGerald, LM and Kibel, AS and Drake, BF and Vega, A and Gómez-Caamaño, A and Szulkin, R and Eklund, M and Kogevinas, M and Llorca, J and Castaño-Vinyals, G and Penney, KL and Stampfer, M and Park, JY and Sellers, TA and Lin, HY and Stanford, JL and Cybulski, C and Wokolorczyk, D and Lubinski, J and Ostrander, EA and Geybels, MS and Nordestgaard, BG and Nielsen, SF and Weischer, M and Bisbjerg, R and Røder, MA and Iversen, P and Brenner, H and Cuk, K and Holleczek, B and Maier, C and Luedeke, M and Schnoeller, T and Kim, J and Logothetis, CJ and John, EM and Teixeira, MR and Paulo, P and Cardoso, M and Neuhausen, SL and Steele, L and Ding, YC and De Ruyck, K and De Meerleer, G and Ost, P and Razack, A and Lim, J and Teo, SH and Lin, DW and Newcomb, LF and Lessel, D and Gamulin, M and Kulis, T and Kaneva, R and Usmani, N and Singhal, S and Slavov, C and Mitev, V and Parliament, M and Claessens, F and Joniau, S and Van den Broeck, T and Larkin, S and Townsend, PA and Aukim-Hastie, C and Gago-Dominguez, M and Castelao, JE and Martinez, ME and Roobol, MJ and Jenster, G and van Schaik, RHN and Menegaux, F and Truong, T and Koudou, YA and Xu, J and Khaw, KT and Cannon-Albright, L and Pandha, H and Michael, A and Thibodeau, SN and McDonnell, SK and Schaid, DJ and Lindstrom, S and Turman, C and Ma, J and Hunter, DJ and Riboli, E and Siddiq, A and Canzian, F and Kolonel, LN and Le Marchand, L and Hoover, RN and Machiela, MJ and Cui, Z and Kraft, P and Amos, CI and Conti, DV and Easton, DF and Wiklund, F and Chanock, SJ and Henderson, BE and Kote-Jarai, Z and Haiman, CA and Eeles, RA and , and , and , and , and , and , and , and , and , }, title = {Association analyses of more than 140,000 men identify 63 new prostate cancer susceptibility loci.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {928-936}, doi = {10.1038/s41588-018-0142-8}, pmid = {29892016}, issn = {1546-1718}, support = {K07 CA187546/CA/NCI NIH HHS/United States ; UM1 CA182883/CA/NCI NIH HHS/United States ; }, abstract = {Genome-wide association studies (GWAS) and fine-mapping efforts to date have identified more than 100 prostate cancer (PrCa)-susceptibility loci. We meta-analyzed genotype data from a custom high-density array of 46,939 PrCa cases and 27,910 controls of European ancestry with previously genotyped data of 32,255 PrCa cases and 33,202 controls of European ancestry. Our analysis identified 62 novel loci associated (P < 5.0 × 10-8) with PrCa and one locus significantly associated with early-onset PrCa (≤55 years). Our findings include missense variants rs1800057 (odds ratio (OR) = 1.16; P = 8.2 × 10-9; G>C, p.Pro1054Arg) in ATM and rs2066827 (OR = 1.06; P = 2.3 × 10-9; T>G, p.Val109Gly) in CDKN1B. The combination of all loci captured 28.4% of the PrCa familial relative risk, and a polygenic risk score conferred an elevated PrCa risk for men in the ninetieth to ninety-ninth percentiles (relative risk = 2.69; 95% confidence interval (CI): 2.55-2.82) and first percentile (relative risk = 5.71; 95% CI: 5.04-6.48) risk stratum compared with the population average. These findings improve risk prediction, enhance fine-mapping, and provide insight into the underlying biology of PrCa1.}, } @article {pmid29892015, year = {2018}, author = {Roselli, C and Chaffin, MD and Weng, LC and Aeschbacher, S and Ahlberg, G and Albert, CM and Almgren, P and Alonso, A and Anderson, CD and Aragam, KG and Arking, DE and Barnard, J and Bartz, TM and Benjamin, EJ and Bihlmeyer, NA and Bis, JC and Bloom, HL and Boerwinkle, E and Bottinger, EB and Brody, JA and Calkins, H and Campbell, A and Cappola, TP and Carlquist, J and Chasman, DI and Chen, LY and Chen, YI and Choi, EK and Choi, SH and Christophersen, IE and Chung, MK and Cole, JW and Conen, D and Cook, J and Crijns, HJ and Cutler, MJ and Damrauer, SM and Daniels, BR and Darbar, D and Delgado, G and Denny, JC and Dichgans, M and Dörr, M and Dudink, EA and Dudley, SC and Esa, N and Esko, T and Eskola, M and Fatkin, D and Felix, SB and Ford, I and Franco, OH and Geelhoed, B and Grewal, RP and Gudnason, V and Guo, X and Gupta, N and Gustafsson, S and Gutmann, R and Hamsten, A and Harris, TB and Hayward, C and Heckbert, SR and Hernesniemi, J and Hocking, LJ and Hofman, A and Horimoto, ARVR and Huang, J and Huang, PL and Huffman, J and Ingelsson, E and Ipek, EG and Ito, K and Jimenez-Conde, J and Johnson, R and Jukema, JW and Kääb, S and Kähönen, M and Kamatani, Y and Kane, JP and Kastrati, A and Kathiresan, S and Katschnig-Winter, P and Kavousi, M and Kessler, T and Kietselaer, BL and Kirchhof, P and Kleber, ME and Knight, S and Krieger, JE and Kubo, M and Launer, LJ and Laurikka, J and Lehtimäki, T and Leineweber, K and Lemaitre, RN and Li, M and Lim, HE and Lin, HJ and Lin, H and Lind, L and Lindgren, CM and Lokki, ML and London, B and Loos, RJF and Low, SK and Lu, Y and Lyytikäinen, LP and Macfarlane, PW and Magnusson, PK and Mahajan, A and Malik, R and Mansur, AJ and Marcus, GM and Margolin, L and Margulies, KB and März, W and McManus, DD and Melander, O and Mohanty, S and Montgomery, JA and Morley, MP and Morris, AP and Müller-Nurasyid, M and Natale, A and Nazarian, S and Neumann, B and Newton-Cheh, C and Niemeijer, MN and Nikus, K and Nilsson, P and Noordam, R and Oellers, H and Olesen, MS and Orho-Melander, M and Padmanabhan, S and Pak, HN and Paré, G and Pedersen, NL and Pera, J and Pereira, A and Porteous, D and Psaty, BM and Pulit, SL and Pullinger, CR and Rader, DJ and Refsgaard, L and Ribasés, M and Ridker, PM and Rienstra, M and Risch, L and Roden, DM and Rosand, J and Rosenberg, MA and Rost, N and Rotter, JI and Saba, S and Sandhu, RK and Schnabel, RB and Schramm, K and Schunkert, H and Schurman, C and Scott, SA and Seppälä, I and Shaffer, C and Shah, S and Shalaby, AA and Shim, J and Shoemaker, MB and Siland, JE and Sinisalo, J and Sinner, MF and Slowik, A and Smith, AV and Smith, BH and Smith, JG and Smith, JD and Smith, NL and Soliman, EZ and Sotoodehnia, N and Stricker, BH and Sun, A and Sun, H and Svendsen, JH and Tanaka, T and Tanriverdi, K and Taylor, KD and Teder-Laving, M and Teumer, A and Thériault, S and Trompet, S and Tucker, NR and Tveit, A and Uitterlinden, AG and Van Der Harst, P and Van Gelder, IC and Van Wagoner, DR and Verweij, N and Vlachopoulou, E and Völker, U and Wang, B and Weeke, PE and Weijs, B and Weiss, R and Weiss, S and Wells, QS and Wiggins, KL and Wong, JA and Woo, D and Worrall, BB and Yang, PS and Yao, J and Yoneda, ZT and Zeller, T and Zeng, L and Lubitz, SA and Lunetta, KL and Ellinor, PT}, title = {Multi-ethnic genome-wide association study for atrial fibrillation.}, journal = {Nature genetics}, volume = {50}, number = {9}, pages = {1225-1233}, pmid = {29892015}, issn = {1546-1718}, support = {R01 HL139731/HL/NHLBI NIH HHS/United States ; K24 HL105780/HL/NHLBI NIH HHS/United States ; L30 HL123413/HL/NHLBI NIH HHS/United States ; R01 HL092577/HL/NHLBI NIH HHS/United States ; T32 GM007569/GM/NIGMS NIH HHS/United States ; R01 HL128914/HL/NHLBI NIH HHS/United States ; K23 HL127296/HL/NHLBI NIH HHS/United States ; 2014105//Doris Duke Charitable Foundation/United States ; R01 HL116747/HL/NHLBI NIH HHS/United States ; }, abstract = {Atrial fibrillation (AF) affects more than 33 million individuals worldwide1 and has a complex heritability2. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.}, } @article {pmid29892014, year = {2018}, author = {Kovacs, L and Chao-Chu, J and Schneider, S and Gottardo, M and Tzolovsky, G and Dzhindzhev, NS and Riparbelli, MG and Callaini, G and Glover, DM}, title = {Gorab is a Golgi protein required for structure and duplication of Drosophila centrioles.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {1021-1031}, pmid = {29892014}, issn = {1546-1718}, support = {202855//Wellcome Trust/United Kingdom ; A18795//Cancer Research UK/United Kingdom ; }, abstract = {We demonstrate that a Drosophila Golgi protein, Gorab, is present not only in the trans-Golgi but also in the centriole cartwheel where, complexed to Sas6, it is required for centriole duplication. In addition to centriole defects, flies lacking Gorab are uncoordinated due to defects in sensory cilia, which lose their nine-fold symmetry. We demonstrate the separation of centriole and Golgi functions of Drosophila Gorab in two ways: first, we have created Gorab variants that are unable to localize to trans-Golgi but can still rescue the centriole and cilia defects of gorab null flies; second, we show that expression of C-terminally tagged Gorab disrupts Golgi functions in cytokinesis of male meiosis, a dominant phenotype overcome by mutations preventing Golgi targeting. Our findings suggest that during animal evolution, a Golgi protein has arisen with a second, apparently independent, role in centriole duplication.}, } @article {pmid29892013, year = {2018}, author = {Loh, PR and Kichaev, G and Gazal, S and Schoech, AP and Price, AL}, title = {Mixed-model association for biobank-scale datasets.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {906-908}, doi = {10.1038/s41588-018-0144-6}, pmid = {29892013}, issn = {1546-1718}, support = {R01 GM105857/GM/NIGMS NIH HHS/United States ; R01 HG006399/HG/NHGRI NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; U01 HG009379/HG/NHGRI NIH HHS/United States ; }, } @article {pmid29892012, year = {2018}, author = {Chen, S and Fragoza, R and Klei, L and Liu, Y and Wang, J and Roeder, K and Devlin, B and Yu, H}, title = {An interactome perturbation framework prioritizes damaging missense mutations for developmental disorders.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {1032-1040}, doi = {10.1038/s41588-018-0130-z}, pmid = {29892012}, issn = {1546-1718}, support = {R37 MH057881/MH/NIMH NIH HHS/United States ; R01 CA167824/CA/NCI NIH HHS/United States ; R01 GM125639/GM/NIGMS NIH HHS/United States ; R01 HD082568/HD/NICHD NIH HHS/United States ; R01 GM124559/GM/NIGMS NIH HHS/United States ; UM1 HG009393/HG/NHGRI NIH HHS/United States ; R01 GM104424/GM/NIGMS NIH HHS/United States ; }, abstract = {Identifying disease-associated missense mutations remains a challenge, especially in large-scale sequencing studies. Here we establish an experimentally and computationally integrated approach to investigate the functional impact of missense mutations in the context of the human interactome network and test our approach by analyzing ~2,000 de novo missense mutations found in autism subjects and their unaffected siblings. Interaction-disrupting de novo missense mutations are more common in autism probands, principally affect hub proteins, and disrupt a significantly higher fraction of hub interactions than in unaffected siblings. Moreover, they tend to disrupt interactions involving genes previously implicated in autism, providing complementary evidence that strengthens previously identified associations and enhances the discovery of new ones. Importantly, by analyzing de novo missense mutation data from six disorders, we demonstrate that our interactome perturbation approach offers a generalizable framework for identifying and prioritizing missense mutations that contribute to the risk of human disease.}, } @article {pmid29891866, year = {2018}, author = {Delmont, TO and Quince, C and Shaiber, A and Esen, ÖC and Lee, ST and Rappé, MS and McLellan, SL and Lücker, S and Eren, AM}, title = {Nitrogen-fixing populations of Planctomycetes and Proteobacteria are abundant in surface ocean metagenomes.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {804-813}, doi = {10.1038/s41564-018-0176-9}, pmid = {29891866}, issn = {2058-5276}, abstract = {Nitrogen fixation in the surface ocean impacts global marine nitrogen bioavailability and thus microbial primary productivity. Until now, cyanobacterial populations have been viewed as the main suppliers of bioavailable nitrogen in this habitat. Although PCR amplicon surveys targeting the nitrogenase reductase gene have revealed the existence of diverse non-cyanobacterial diazotrophic populations, subsequent quantitative PCR surveys suggest that they generally occur in low abundance. Here, we use state-of-the-art metagenomic assembly and binning strategies to recover nearly one thousand non-redundant microbial population genomes from the TARA Oceans metagenomes. Among these, we provide the first genomic evidence for non-cyanobacterial diazotrophs inhabiting surface waters of the open ocean, which correspond to lineages within the Proteobacteria and, most strikingly, the Planctomycetes. Members of the latter phylum are prevalent in aquatic systems, but have never been linked to nitrogen fixation previously. Moreover, using genome-wide quantitative read recruitment, we demonstrate that the discovered diazotrophs were not only widespread but also remarkably abundant (up to 0.3% of metagenomic reads for a single population) in both the Pacific Ocean and the Atlantic Ocean northwest. Our results extend decades of PCR-based gene surveys, and substantiate the importance of heterotrophic bacteria in the fixation of nitrogen in the surface ocean.}, } @article {pmid29891865, year = {2018}, author = {Chougui, G and Munir-Matloob, S and Matkovic, R and Martin, MM and Morel, M and Lahouassa, H and Leduc, M and Ramirez, BC and Etienne, L and Margottin-Goguet, F}, title = {HIV-2/SIV viral protein X counteracts HUSH repressor complex.}, journal = {Nature microbiology}, volume = {3}, number = {8}, pages = {891-897}, doi = {10.1038/s41564-018-0179-6}, pmid = {29891865}, issn = {2058-5276}, abstract = {To evade host immune defences, human immunodeficiency viruses 1 and 2 (HIV-1 and HIV-2) have evolved auxiliary proteins that target cell restriction factors. Viral protein X (Vpx) from the HIV-2/SIVsmm lineage enhances viral infection by antagonizing SAMHD1 (refs 1,2), but this antagonism is not sufficient to explain all Vpx phenotypes. Here, through a proteomic screen, we identified another Vpx target-HUSH (TASOR, MPP8 and periphilin)-a complex involved in position-effect variegation3. HUSH downregulation by Vpx is observed in primary cells and HIV-2-infected cells. Vpx binds HUSH and induces its proteasomal degradation through the recruitment of the DCAF1 ubiquitin ligase adaptor, independently from SAMHD1 antagonism. As a consequence, Vpx is able to reactivate HIV latent proviruses, unlike Vpx mutants, which are unable to induce HUSH degradation. Although antagonism of human HUSH is not conserved among all lentiviral lineages including HIV-1, it is a feature of viral protein R (Vpr) from simian immunodeficiency viruses (SIVs) of African green monkeys and from the divergent SIV of l'Hoest's monkey, arguing in favour of an ancient lentiviral species-specific vpx/vpr gene function. Altogether, our results suggest the HUSH complex as a restriction factor, active in primary CD4+ T cells and counteracted by Vpx, therefore providing a molecular link between intrinsic immunity and epigenetic control.}, } @article {pmid29891864, year = {2018}, author = {Ellison, CK and Dalia, TN and Vidal Ceballos, A and Wang, JC and Biais, N and Brun, YV and Dalia, AB}, title = {Retraction of DNA-bound type IV competence pili initiates DNA uptake during natural transformation in Vibrio cholerae.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {773-780}, doi = {10.1038/s41564-018-0174-y}, pmid = {29891864}, issn = {2058-5276}, support = {SC2 AI116566/AI/NIAID NIH HHS/United States ; }, abstract = {Natural transformation is a broadly conserved mechanism of horizontal gene transfer in bacterial species that can shape evolution and foster the spread of antibiotic resistance determinants, promote antigenic variation and lead to the acquisition of novel virulence factors. Surface appendages called competence pili promote DNA uptake during the first step of natural transformation 1 ; however, their mechanism of action has remained unclear owing to an absence of methods to visualize these structures in live cells. Here, using the model naturally transformable species Vibrio cholerae and a pilus-labelling method, we define the mechanism for type IV competence pilus-mediated DNA uptake during natural transformation. First, we show that type IV competence pili bind to extracellular double-stranded DNA via their tip and demonstrate that this binding is critical for DNA uptake. Next, we show that type IV competence pili are dynamic structures and that pilus retraction brings tip-bound DNA to the cell surface. Finally, we show that pilus retraction is spatiotemporally coupled to DNA internalization and that sterically obstructing pilus retraction prevents DNA uptake. Together, these results indicate that type IV competence pili directly bind to DNA via their tip and mediate DNA internalization through retraction during this conserved mechanism of horizontal gene transfer.}, } @article {pmid29891863, year = {2018}, author = {Schofield, CJ}, title = {Antibiotics as food for bacteria.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {752-753}, doi = {10.1038/s41564-018-0181-z}, pmid = {29891863}, issn = {2058-5276}, } @article {pmid29891721, year = {2018}, author = {Dai, J and Liang, K and Zhao, S and Jia, W and Liu, Y and Wu, H and Lv, J and Cao, C and Chen, T and Zhuang, S and Hou, X and Zhou, S and Zhang, X and Chen, XW and Huang, Y and Xiao, RP and Wang, YL and Luo, T and Xiao, J and Wang, C}, title = {Chemoproteomics reveals baicalin activates hepatic CPT1 to ameliorate diet-induced obesity and hepatic steatosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5896-E5905}, pmid = {29891721}, issn = {1091-6490}, mesh = {Allosteric Regulation/drug effects ; Animals ; Binding Sites ; Carnitine O-Palmitoyltransferase/*metabolism ; Diet/adverse effects ; Enzyme Activation/drug effects ; *Fatty Liver/chemically induced/enzymology/pathology/prevention & control ; Flavonoids/*pharmacology ; HeLa Cells ; Humans ; Liver/*enzymology/pathology ; Mice ; Mitochondria, Liver/*enzymology/pathology ; *Obesity/chemically induced/enzymology/prevention & control ; *Proteomics ; }, abstract = {Obesity and related metabolic diseases are becoming worldwide epidemics that lead to increased death rates and heavy health care costs. Effective treatment options have not been found yet. Here, based on the observation that baicalin, a flavonoid from the herbal medicine Scutellaria baicalensis, has unique antisteatosis activity, we performed quantitative chemoproteomic profiling and identified carnitine palmitoyltransferase 1 (CPT1), the controlling enzyme for fatty acid oxidation, as the key target of baicalin. The flavonoid directly activated hepatic CPT1 with isoform selectivity to accelerate the lipid influx into mitochondria for oxidation. Chronic treatment of baicalin ameliorated diet-induced obesity (DIO) and hepatic steatosis and led to systemic improvement of other metabolic disorders. Disruption of the predicted binding site of baicalin on CPT1 completely abolished the beneficial effect of the flavonoid. Our discovery of baicalin as an allosteric CPT1 activator opens new opportunities for pharmacological treatment of DIO and associated sequelae.}, } @article {pmid29891720, year = {2018}, author = {Ishii, HA and Bradley, JP and Bechtel, HA and Brownlee, DE and Bustillo, KC and Ciston, J and Cuzzi, JN and Floss, C and Joswiak, DJ}, title = {Multiple generations of grain aggregation in different environments preceded solar system body formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6608-6613}, pmid = {29891720}, issn = {1091-6490}, abstract = {The solar system formed from interstellar dust and gas in a molecular cloud. Astronomical observations show that typical interstellar dust consists of amorphous (a-) silicate and organic carbon. Bona fide physical samples for laboratory studies would yield unprecedented insight about solar system formation, but they were largely destroyed. The most likely repositories of surviving presolar dust are the least altered extraterrestrial materials, interplanetary dust particles (IDPs) with probable cometary origins. Cometary IDPs contain abundant submicron a-silicate grains called GEMS (glass with embedded metal and sulfides), believed to be carbon-free. Some have detectable isotopically anomalous a-silicate components from other stars, proving they are preserved dust inherited from the interstellar medium. However, it is debated whether the majority of GEMS predate the solar system or formed in the solar nebula by condensation of high-temperature (>1,300 K) gas. Here, we map IDP compositions with single nanometer-scale resolution and find that GEMS contain organic carbon. Mapping reveals two generations of grain aggregation, the key process in growth from dust grains to planetesimals, mediated by carbon. GEMS grains, some with a-silicate subgrains mantled by organic carbon, comprise the earliest generation of aggregates. These aggregates (and other grains) are encapsulated in lower-density organic carbon matrix, indicating a second generation of aggregation. Since this organic carbon thermally decomposes above ∼450 K, GEMS cannot have accreted in the hot solar nebula, and formed, instead, in the cold presolar molecular cloud and/or outer protoplanetary disk. We suggest that GEMS are consistent with surviving interstellar dust, condensed in situ, and cycled through multiple molecular clouds.}, } @article {pmid29891719, year = {2018}, author = {Amin, P and Florez, M and Najafov, A and Pan, H and Geng, J and Ofengeim, D and Dziedzic, SA and Wang, H and Barrett, VJ and Ito, Y and LaVoie, MJ and Yuan, J}, title = {Regulation of a distinct activated RIPK1 intermediate bridging complex I and complex II in TNFα-mediated apoptosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5944-E5953}, pmid = {29891719}, issn = {1091-6490}, support = {R01 AG047231/AG/NIA NIH HHS/United States ; T32 AG000222/AG/NIA NIH HHS/United States ; R01 NS082257/NS/NINDS NIH HHS/United States ; RF1 AG055521/AG/NIA NIH HHS/United States ; T32 GM007306/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Apoptosis ; Cell Line ; Enzyme Activation ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics/metabolism ; Mice ; Mice, Knockout ; Proto-Oncogene Proteins c-cbl/genetics/metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/*metabolism ; Tumor Necrosis Factor-alpha/genetics/*metabolism ; *Ubiquitination ; }, abstract = {Stimulation of cells with TNFα can promote distinct cell death pathways, including RIPK1-independent apoptosis, necroptosis, and RIPK1-dependent apoptosis (RDA)-the latter of which we still know little about. Here we show that RDA involves the rapid formation of a distinct detergent-insoluble, highly ubiquitinated, and activated RIPK1 pool, termed "iuRIPK1." iuRIPK1 forms after RIPK1 activation in TNF-receptor-associated complex I, and before cytosolic complex II formation and caspase activation. To identify regulators of iuRIPK1 formation and RIPK1 activation in RDA, we conducted a targeted siRNA screen of 1,288 genes. We found that NEK1, whose loss-of-function mutations have been identified in 3% of ALS patients, binds to activated RIPK1 and restricts RDA by negatively regulating formation of iuRIPK1, while LRRK2, a kinase implicated in Parkinson's disease, promotes RIPK1 activation and association with complex I in RDA. Further, the E3 ligases APC11 and c-Cbl promote RDA, and c-Cbl is recruited to complex I in RDA, where it promotes prodeath K63-ubiquitination of RIPK1 to lead to iuRIPK1 formation. Finally, we show that two different modes of necroptosis induction by TNFα exist which are differentially regulated by iuRIPK1 formation. Overall, this work reveals a distinct mechanism of RIPK1 activation that mediates the signaling mechanism of RDA as well as a type of necroptosis.}, } @article {pmid29891718, year = {2018}, author = {Smith, CCR and Tittes, S and Mendieta, JP and Collier-Zans, E and Rowe, HC and Rieseberg, LH and Kane, NC}, title = {Genetics of alternative splicing evolution during sunflower domestication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6768-6773}, pmid = {29891718}, issn = {1091-6490}, mesh = {*Alternative Splicing ; Domestication ; *Evolution, Molecular ; Helianthus/*genetics ; Plant Breeding ; Plant Proteins/genetics/metabolism ; Protein Isoforms/genetics/metabolism ; Quantitative Trait Loci ; RNA, Plant/*genetics ; Spliceosomes ; Transcriptome ; }, abstract = {Alternative splicing enables organisms to produce the diversity of proteins necessary for multicellular life by using relatively few protein-coding genes. Although differences in splicing have been identified among divergent taxa, the shorter-term evolution of splicing is understudied. The origins of novel splice forms, and the contributions of alternative splicing to major evolutionary transitions, are largely unknown. This study used transcriptomes of wild and domesticated sunflowers to examine splice differentiation and regulation during domestication. We identified substantial splicing divergence between wild and domesticated sunflowers, mainly in the form of intron retention. Transcripts with divergent splicing were enriched for seed-development functions, suggesting that artificial selection impacted splicing patterns. Mapping of quantitative trait loci (QTLs) associated with 144 differential splicing cases revealed primarily trans-acting variation affecting splicing patterns. A large proportion of identified QTLs contain known spliceosome proteins and are associated with splicing variation in multiple genes. Examining a broader set of wild and domesticated sunflower genotypes revealed that most differential splicing patterns in domesticated sunflowers likely arose from standing variation in wild Helianthus annuus and gained frequency during the domestication process. However, several domesticate-associated splicing patterns appear to be introgressed from other Helianthus species. These results suggest that sunflower domestication involved selection on pleiotropic regulatory alleles. More generally, our findings indicate that substantial differences in isoform abundances arose rapidly during a recent evolutionary transition and appear to contribute to adaptation and population divergence.}, } @article {pmid29891717, year = {2018}, author = {Lujan, AL and Croci, DO and Gambarte Tudela, JA and Losinno, AD and Cagnoni, AJ and Mariño, KV and Damiani, MT and Rabinovich, GA}, title = {Glycosylation-dependent galectin-receptor interactions promote Chlamydia trachomatis infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6000-E6009}, pmid = {29891717}, issn = {1091-6490}, mesh = {Animals ; Bacterial Proteins/genetics/*metabolism ; Chlamydia trachomatis/genetics/*metabolism ; Female ; Galectin 1/genetics/*metabolism ; HeLa Cells ; Humans ; Lymphogranuloma Venereum/genetics/*metabolism/pathology ; Male ; Mice ; }, abstract = {Chlamydia trachomatis (Ct) constitutes the most prevalent sexually transmitted bacterium worldwide. Chlamydial infections can lead to severe clinical sequelae including pelvic inflammatory disease, ectopic pregnancy, and tubal infertility. As an obligate intracellular pathogen, Ct has evolved multiple strategies to promote adhesion and invasion of host cells, including those involving both bacterial and host glycans. Here, we show that galectin-1 (Gal1), an endogenous lectin widely expressed in female and male genital tracts, promotes Ct infection. Through glycosylation-dependent mechanisms involving recognition of bacterial glycoproteins and N-glycosylated host cell receptors, Gal1 enhanced Ct attachment to cervical epithelial cells. Exposure to Gal1, mainly in its dimeric form, facilitated bacterial entry and increased the number of infected cells by favoring Ct-Ct and Ct-host cell interactions. These effects were substantiated in vivo in mice lacking Gal1 or complex β1-6-branched N-glycans. Thus, disrupting Gal1-N-glycan interactions may limit the severity of chlamydial infection by inhibiting bacterial invasion of host cells.}, } @article {pmid29891716, year = {2018}, author = {}, title = {Correction for Zhu et al., CSI1, PATROL1, and exocyst complex cooperate in delivery of cellulose synthase complexes to the plasma membrane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5635}, doi = {10.1073/pnas.1808743115}, pmid = {29891716}, issn = {1091-6490}, } @article {pmid29891715, year = {2018}, author = {Herrmann, DL and Schifman, LA and Shuster, WD}, title = {Widespread loss of intermediate soil horizons in urban landscapes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6751-6755}, pmid = {29891715}, issn = {1091-6490}, mesh = {Cities ; Databases, Factual ; *Ecosystem ; *Soil ; *Urbanization ; }, abstract = {Soils support terrestrial ecosystem function and therefore are critical urban infrastructure for generating ecosystem services. Urbanization processes modify ecosystem function by changing the layers of soils identified as soil horizons. Soil horizons are integrative proxies for suites of soil properties and as such can be used as an observable unit to track modifications within soil profiles. Here, in an analysis of 11 cities representing 10 of the 12 soil orders, we show that urban soils have ∼50% fewer soil horizons than preurban soils. Specifically, B horizons were much less common in urban soils and were replaced by a deepening of A horizons and a shallowing of C horizons. This shift is likely due to two processes: (i) local management, i.e., soil removal, mixing, and fill additions, and (ii) soil development timelines, i.e., urbanized soils are young and have had short time periods for soil horizon development since urbanization (decades to centuries) relative to soil formation before urbanization (centuries to millennia). Urban soils also deviated from the standard A-B-C horizon ordering at a much greater frequency than preurban soils. Overall, our finding of common shifts in urban soil profiles across soil orders and cities suggests that urban soils may function differently from their preurban antecedents. This work introduces a basis for improving our understanding of soil modifications by urbanization and its potential effects on ecosystem functioning and thereby has implications for ecosystem services derived from urban landscapes.}, } @article {pmid29891714, year = {2018}, author = {Zhang, Y and Dallner, OS and Nakadai, T and Fayzikhodjaeva, G and Lu, YH and Lazar, MA and Roeder, RG and Friedman, JM}, title = {A noncanonical PPARγ/RXRα-binding sequence regulates leptin expression in response to changes in adipose tissue mass.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6039-E6047}, pmid = {29891714}, issn = {1091-6490}, support = {R01 DK049780/DK/NIDDK NIH HHS/United States ; R01 DK071900/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adipocytes/cytology/*metabolism ; Adipose Tissue/cytology/*metabolism ; Animals ; Cell Line ; *Gene Expression Regulation ; *Leptin/biosynthesis/genetics ; Mice ; Mice, Obese ; *PPAR gamma ; *Response Elements ; *Retinoid X Receptor alpha ; }, abstract = {Leptin expression decreases after fat loss and is increased when obesity develops, and its proper quantitative regulation is essential for the homeostatic control of fat mass. We previously reported that a distant leptin enhancer 1 (LE1), 16 kb upstream from the transcription start site (TSS), confers fat-specific expression in a bacterial artificial chromosome transgenic (BACTG) reporter mouse. However, this and the other elements that we identified do not account for the quantitative changes in leptin expression that accompany alterations of adipose mass. In this report, we used an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) to identify a 17-bp noncanonical peroxisome proliferator-activated receptor gamma (PPARγ)/retinoid X receptor alpha (RXRα)-binding site, leptin regulatory element 1 (LepRE1), within LE1, and show that it is necessary for the fat-regulated quantitative control of reporter (luciferase) expression. While BACTG reporter mice with mutations in this sequence still show fat-specific expression, luciferase is no longer decreased after food restriction and weight loss. Similarly, the increased expression of leptin reporter associated with obesity in ob/ob mice is impaired. A functionally analogous LepRE1 site is also found in a second, redundant DNA regulatory element 13 kb downstream of the TSS. These data uncouple the mechanisms conferring qualitative and quantitative expression of the leptin gene and further suggest that factor(s) that bind to LepRE1 quantitatively control leptin expression and might be components of a lipid-sensing system in adipocytes.}, } @article {pmid29891713, year = {2018}, author = {Slavi, N and Toychiev, AH and Kosmidis, S and Ackert, J and Bloomfield, SA and Wulff, H and Viswanathan, S and Lampe, PD and Srinivas, M}, title = {Suppression of connexin 43 phosphorylation promotes astrocyte survival and vascular regeneration in proliferative retinopathy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5934-E5943}, pmid = {29891713}, issn = {1091-6490}, support = {R01 EY028170/EY/NEI NIH HHS/United States ; R01 EY007360/EY/NEI NIH HHS/United States ; R01 EY026024/EY/NEI NIH HHS/United States ; R01 GM055632/GM/NIGMS NIH HHS/United States ; R01 NS100294/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Astrocytes/*metabolism/pathology ; Casein Kinase Idelta/metabolism ; Cell Hypoxia ; Cell Survival ; Connexin 43/*metabolism ; Female ; Male ; Mice ; Phosphorylation ; *Regeneration ; Retinal Vessels/*physiology ; Vitreoretinopathy, Proliferative/*metabolism/pathology/physiopathology ; }, abstract = {Degeneration of retinal astrocytes precedes hypoxia-driven pathologic neovascularization and vascular leakage in ischemic retinopathies. However, the molecular events that underlie astrocyte loss remain unclear. Astrocytes abundantly express connexin 43 (Cx43), a transmembrane protein that forms gap junction (GJ) channels and hemichannels. Cx channels can transfer toxic signals from dying cells to healthy neighbors under pathologic conditions. Here we show that Cx43 plays a critical role in astrocyte apoptosis and the resulting preretinal neovascularization in a mouse model of oxygen-induced retinopathy. Opening of Cx43 hemichannels was not observed following hypoxia. In contrast, GJ coupling between astrocytes increased, which could lead to amplification of injury. Accordingly, conditional deletion of Cx43 maintained a higher density of astrocytes in the hypoxic retina. We also identify a role for Cx43 phosphorylation in mediating these processes. Increased coupling in response to hypoxia is due to phosphorylation of Cx43 by casein kinase 1δ (CK1δ). Suppression of this phosphorylation using an inhibitor of CK1δ or in site-specific phosphorylation-deficient mice similarly protected astrocytes from hypoxic damage. Rescue of astrocytes led to restoration of a functional retinal vasculature and lowered the hypoxic burden, thereby curtailing neovascularization and neuroretinal dysfunction. We also find that absence of astrocytic Cx43 does not affect developmental angiogenesis or neuronal function in normoxic retinas. Our in vivo work directly links phosphorylation of Cx43 to astrocytic coupling and apoptosis and ultimately to vascular regeneration in retinal ischemia. This study reveals that targeting Cx43 phosphorylation in astrocytes is a potential direction for the treatment of proliferative retinopathies.}, } @article {pmid29891712, year = {2018}, author = {Liko, I and Degiacomi, MT and Lee, S and Newport, TD and Gault, J and Reading, E and Hopper, JTS and Housden, NG and White, P and Colledge, M and Sula, A and Wallace, BA and Kleanthous, C and Stansfeld, PJ and Bayley, H and Benesch, JLP and Allison, TM and Robinson, CV}, title = {Lipid binding attenuates channel closure of the outer membrane protein OmpF.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6691-6696}, pmid = {29891712}, issn = {1091-6490}, support = {BB/L006790//Biotechnology and Biological Sciences Research Council/United Kingdom ; 104633/Z/14/Z//Wellcome Trust/United Kingdom ; //Medical Research Council/United Kingdom ; BB/L021234/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L026251//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Bacterial Outer Membrane Proteins/chemistry/metabolism ; Cation Transport Proteins/chemistry/metabolism ; Escherichia coli Proteins/chemistry/metabolism ; Hydrogen-Ion Concentration ; Models, Chemical ; Models, Molecular ; Molecular Dynamics Simulation ; Phosphatidylcholines/*metabolism ; Phosphatidylglycerols/*metabolism ; Porins/chemistry/*metabolism ; Protein Binding ; Protein Conformation ; Spectrometry, Mass, Electrospray Ionization ; Voltage-Dependent Anion Channels/chemistry/metabolism ; Voltage-Gated Sodium Channels/chemistry/metabolism ; }, abstract = {Strong interactions between lipids and proteins occur primarily through association of charged headgroups and amino acid side chains, rendering the protonation status of both partners important. Here we use native mass spectrometry to explore lipid binding as a function of charge of the outer membrane porin F (OmpF). We find that binding of anionic phosphatidylglycerol (POPG) or zwitterionic phosphatidylcholine (POPC) to OmpF is sensitive to electrospray polarity while the effects of charge are less pronounced for other proteins in outer or mitochondrial membranes: the ferripyoverdine receptor (FpvA) or the voltage-dependent anion channel (VDAC). Only marginal charge-induced differences were observed for inner membrane proteins: the ammonia channel (AmtB) or the mechanosensitive channel. To understand these different sensitivities, we performed an extensive bioinformatics analysis of membrane protein structures and found that OmpF, and to a lesser extent FpvA and VDAC, have atypically high local densities of basic and acidic residues in their lipid headgroup-binding regions. Coarse-grained molecular dynamics simulations, in mixed lipid bilayers, further implicate changes in charge by demonstrating preferential binding of anionic POPG over zwitterionic POPC to protonated OmpF, an effect not observed to the same extent for AmtB. Moreover, electrophysiology and mass-spectrometry-based ligand-binding experiments, at low pH, show that POPG can maintain OmpF channels in open conformations for extended time periods. Since the outer membrane is composed almost entirely of anionic lipopolysaccharide, with similar headgroup properties to POPG, such anionic lipid binding could prevent closure of OmpF channels, thereby increasing access of antibiotics that use porin-mediated pathways.}, } @article {pmid29891711, year = {2018}, author = {Wang, F and Lee, J and Phillips, DJ and Holliday, SG and Chua, SL and Bravo-Abad, J and Joannopoulos, JD and Soljačić, M and Johnson, SG and Everitt, HO}, title = {A high-efficiency regime for gas-phase terahertz lasers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6614-6619}, pmid = {29891711}, issn = {1091-6490}, abstract = {We present both an innovative theoretical model and an experimental validation of a molecular gas optically pumped far-infrared (OPFIR) laser at 0.25 THz that exhibits 10× greater efficiency (39% of the Manley-Rowe limit) and 1,000× smaller volume than comparable commercial lasers. Unlike previous OPFIR-laser models involving only a few energy levels that failed even qualitatively to match experiments at high pressures, our ab initio theory matches experiments quantitatively, within experimental uncertainties with no free parameters, by accurately capturing the interplay of millions of degrees of freedom in the laser. We show that previous OPFIR lasers were inefficient simply by being too large and that high powers favor high pressures and small cavities. We believe that these results will revive interest in OPFIR laser as a powerful and compact source of terahertz radiation.}, } @article {pmid29891710, year = {2018}, author = {Ryb, U and Eiler, JM}, title = {Oxygen isotope composition of the Phanerozoic ocean and a possible solution to the dolomite problem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6602-6607}, pmid = {29891710}, issn = {1091-6490}, mesh = {Calcium Carbonate/*chemistry ; Climate Change/*history ; Fossils ; Geologic Sediments/*chemistry ; History, Ancient ; Magnesium/*chemistry ; Oceans and Seas ; Oxygen/*analysis ; Oxygen Isotopes/*analysis ; Seawater/*chemistry ; Temperature ; Time Factors ; }, abstract = {The 18O/16O of calcite fossils increased by ∼8‰ between the Cambrian and present. It has long been controversial whether this change reflects evolution in the δ18O of seawater, or a decrease in ocean temperatures, or greater extents of diagenesis of older strata. Here, we present measurements of the oxygen and ‟clumped" isotope compositions of Phanerozoic dolomites and compare these data with published oxygen isotope studies of carbonate rocks. We show that the δ18O values of dolomites and calcite fossils of similar age overlap one another, suggesting they are controlled by similar processes. Clumped isotope measurements of Cambrian to Pleistocene dolomites imply crystallization temperatures of 15-158 °C and parent waters having δ18OVSMOW values from -2 to +12‰. These data are consistent with dolomitization through sediment/rock reaction with seawater and diagenetically modified seawater, over timescales of 100 My, and suggest that, like dolomite, temporal variations of the calcite fossil δ18O record are largely driven by diagenetic alteration. We find no evidence that Phanerozoic seawater was significantly lower in δ18O than preglacial Cenozoic seawater. Thus, the fluxes of oxygen-isotope exchange associated with weathering and hydrothermal alteration reactions have remained stable throughout the Phanerozoic, despite major tectonic, climatic and biologic perturbations. This stability implies that a long-term feedback exists between the global rates of seafloor spreading and weathering. We note that massive dolomites have crystallized in pre-Cenozoic units at temperatures >40 °C. Since Cenozoic platforms generally have not reached such conditions, their thermal immaturity could explain their paucity of dolomites.}, } @article {pmid29891709, year = {2018}, author = {Balister, P and Balogh, J and Bertuzzo, E and Bollobás, B and Caldarelli, G and Maritan, A and Mastrandrea, R and Morris, R and Rinaldo, A}, title = {River landscapes and optimal channel networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6548-6553}, pmid = {29891709}, issn = {1091-6490}, abstract = {We study tree structures termed optimal channel networks (OCNs) that minimize the total gravitational energy loss in the system, an exact property of steady-state landscape configurations that prove dynamically accessible and strikingly similar to natural forms. Here, we show that every OCN is a so-called natural river tree, in the sense that there exists a height function such that the flow directions are always directed along steepest descent. We also study the natural river trees in an arbitrary graph in terms of forbidden substructures, which we call k-path obstacles, and OCNs on a d-dimensional lattice, improving earlier results by determining the minimum energy up to a constant factor for every [Formula: see text] Results extend our capabilities in environmental statistical mechanics.}, } @article {pmid29891708, year = {2018}, author = {Landy, JF and Piazza, J and Goodwin, GP}, title = {Morality traits still dominate in forming impressions of others.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5636}, pmid = {29891708}, issn = {1091-6490}, mesh = {*Attitude ; *Morals ; }, } @article {pmid29891707, year = {2018}, author = {Worm, M and Landgraf, T and Prume, J and Nguyen, H and Kirschbaum, F and von der Emde, G}, title = {Evidence for mutual allocation of social attention through interactive signaling in a mormyrid weakly electric fish.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6852-6857}, pmid = {29891707}, issn = {1091-6490}, mesh = {*Animal Communication ; Animals ; Electric Fish/*physiology ; *Social Behavior ; }, abstract = {Mormyrid weakly electric fish produce electric organ discharges (EODs) for active electrolocation and electrocommunication. These pulses are emitted with variable interdischarge intervals (IDIs) resulting in temporal discharge patterns and interactive signaling episodes with nearby conspecifics. However, unequivocal assignment of interactive signaling to a specific behavioral context has proven to be challenging. Using an ethorobotical approach, we confronted single individuals of weakly electric Mormyrus rume proboscirostris with a mobile fish robot capable of interacting both physically, on arbitrary trajectories, as well as electrically, by generating echo responses through playback of species-specific EODs, thus synchronizing signals with the fish. Interactive signaling by the fish was more pronounced in response to a dynamic echo playback generated by the robot than in response to playback of static random IDI sequences. Such synchronizations were particularly strong at a distance corresponding to the outer limit of active electrolocation, and when fish oriented toward the fish replica. We therefore argue that interactive signaling through echoing of a conspecific's EODs provides a simple mechanism by which weakly electric fish can specifically address nearby individuals during electrocommunication. Echoing may thus enable mormyrids to mutually allocate social attention and constitute a foundation for complex social behavior and relatively advanced cognitive abilities in a basal vertebrate lineage.}, } @article {pmid29891706, year = {2018}, author = {Karig, D and Martini, KM and Lu, T and DeLateur, NA and Goldenfeld, N and Weiss, R}, title = {Stochastic Turing patterns in a synthetic bacterial population.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6572-6577}, pmid = {29891706}, issn = {1091-6490}, mesh = {4-Butyrolactone/analogs & derivatives/physiology ; Bacterial Proteins/physiology ; Binding, Competitive ; Computer Simulation ; Diffusion ; Gene Expression Regulation, Bacterial ; Genes, Reporter ; Homoserine/analogs & derivatives/physiology ; Isopropyl Thiogalactoside/pharmacology ; Ligases/physiology ; *Models, Biological ; Morphogenesis/drug effects/*physiology ; Promoter Regions, Genetic/genetics ; Pseudomonas aeruginosa/drug effects/*growth & development/metabolism ; Quorum Sensing ; Recombinant Proteins/metabolism ; Stochastic Processes ; Trans-Activators/physiology ; Transcription Factors/physiology ; }, abstract = {The origin of biological morphology and form is one of the deepest problems in science, underlying our understanding of development and the functioning of living systems. In 1952, Alan Turing showed that chemical morphogenesis could arise from a linear instability of a spatially uniform state, giving rise to periodic pattern formation in reaction-diffusion systems but only those with a rapidly diffusing inhibitor and a slowly diffusing activator. These conditions are disappointingly hard to achieve in nature, and the role of Turing instabilities in biological pattern formation has been called into question. Recently, the theory was extended to include noisy activator-inhibitor birth and death processes. Surprisingly, this stochastic Turing theory predicts the existence of patterns over a wide range of parameters, in particular with no severe requirement on the ratio of activator-inhibitor diffusion coefficients. To explore whether this mechanism is viable in practice, we have genetically engineered a synthetic bacterial population in which the signaling molecules form a stochastic activator-inhibitor system. The synthetic pattern-forming gene circuit destabilizes an initially homogenous lawn of genetically engineered bacteria, producing disordered patterns with tunable features on a spatial scale much larger than that of a single cell. Spatial correlations of the experimental patterns agree quantitatively with the signature predicted by theory. These results show that Turing-type pattern-forming mechanisms, if driven by stochasticity, can potentially underlie a broad range of biological patterns. These findings provide the groundwork for a unified picture of biological morphogenesis, arising from a combination of stochastic gene expression and dynamical instabilities.}, } @article {pmid29891705, year = {2018}, author = {Ding, H and Lu, L and Shi, Z and Wang, D and Li, L and Li, X and Ren, Y and Liu, C and Cheng, D and Kim, H and Giebink, NC and Wang, X and Yin, L and Zhao, L and Luo, M and Sheng, X}, title = {Microscale optoelectronic infrared-to-visible upconversion devices and their use as injectable light sources.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6632-6637}, pmid = {29891705}, issn = {1091-6490}, mesh = {Animals ; Arsenicals ; Behavior, Animal ; Biocompatible Materials ; Brain Mapping/instrumentation ; Equipment Design ; Gallium ; Infrared Rays ; Mice ; Mice, Nude ; *Miniaturization ; Optogenetics/*instrumentation/methods ; Photons ; *Prostheses and Implants ; Rats ; Semiconductors ; Somatosensory Cortex/physiology ; Subcutaneous Tissue ; }, abstract = {Optical upconversion that converts infrared light into visible light is of significant interest for broad applications in biomedicine, imaging, and displays. Conventional upconversion materials rely on nonlinear light-matter interactions, exhibit incidence-dependent efficiencies, and require high-power excitation. We report an infrared-to-visible upconversion strategy based on fully integrated microscale optoelectronic devices. These thin-film, ultraminiaturized devices realize near-infrared (∼810 nm) to visible [630 nm (red) or 590 nm (yellow)] upconversion that is linearly dependent on incoherent, low-power excitation, with a quantum yield of ∼1.5%. Additional features of this upconversion design include broadband absorption, wide-emission spectral tunability, and fast dynamics. Encapsulated, freestanding devices are transferred onto heterogeneous substrates and show desirable biocompatibilities within biological fluids and tissues. These microscale devices are implanted in behaving animals, with in vitro and in vivo experiments demonstrating their utility for optogenetic neuromodulation. This approach provides a versatile route to achieve upconversion throughout the entire visible spectral range at lower power and higher efficiency than has previously been possible.}, } @article {pmid29891704, year = {2018}, author = {Ma, G and Fan, X and Sheng, P and Fink, M}, title = {Shaping reverberating sound fields with an actively tunable metasurface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6638-6643}, pmid = {29891704}, issn = {1091-6490}, abstract = {A reverberating environment is a common complex medium for airborne sound, with familiar examples such as music halls and lecture theaters. The complexity of reverberating sound fields has hindered their meaningful control. Here, by combining acoustic metasurface and adaptive wavefield shaping, we demonstrate the versatile control of reverberating sound fields in a room. This is achieved through the design and the realization of a binary phase-modulating spatial sound modulator that is based on an actively reconfigurable acoustic metasurface. We demonstrate useful functionalities including the creation of quiet zones and hotspots in a typical reverberating environment.}, } @article {pmid29891703, year = {2018}, author = {Bennett, K and Kowalewski, M and Rouxel, JR and Mukamel, S}, title = {Monitoring molecular nonadiabatic dynamics with femtosecond X-ray diffraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6538-6547}, pmid = {29891703}, issn = {1091-6490}, abstract = {Ultrafast time-resolved X-ray scattering, made possible by free-electron laser sources, provides a wealth of information about electronic and nuclear dynamical processes in molecules. The technique provides stroboscopic snapshots of the time-dependent electronic charge density traditionally used in structure determination and reflects the interplay of elastic and inelastic processes, nonadiabatic dynamics, and electronic populations and coherences. The various contributions to ultrafast off-resonant diffraction from populations and coherences of molecules in crystals, in the gas phase, or from single molecules are surveyed for core-resonant and off-resonant diffraction. Single-molecule [Formula: see text] scaling and two-molecule [Formula: see text] scaling contributions, where N is the number of active molecules, are compared. Simulations are presented for the excited-state nonadiabatic dynamics of the electron harpooning at the avoided crossing in NaF. We show how a class of multiple diffraction signals from a single molecule can reveal charge-density fluctuations through multidimensional correlation functions of the charge density.}, } @article {pmid29891702, year = {2018}, author = {Zhang, M and Yue, J and Cui, R and Ma, Z and Wan, H and Wang, F and Zhu, S and Zhou, Y and Kuang, Y and Zhong, Y and Pang, DW and Dai, H}, title = {Bright quantum dots emitting at ∼1,600 nm in the NIR-IIb window for deep tissue fluorescence imaging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6590-6595}, pmid = {29891702}, issn = {1091-6490}, support = {DP1 NS105737/NS/NINDS NIH HHS/United States ; }, mesh = {Adenocarcinoma/blood supply/secondary ; Animals ; Colonic Neoplasms/pathology ; Drug Stability ; Femoral Artery/ultrastructure ; Femoral Vein/ultrastructure ; *Fluorescent Dyes/analysis/pharmacokinetics/toxicity ; Half-Life ; Hindlimb/blood supply ; Imaging, Three-Dimensional/*methods ; Intravital Microscopy/instrumentation/*methods ; Lead/chemistry ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal/instrumentation/methods ; Microscopy, Electron ; Microscopy, Fluorescence/instrumentation/*methods ; Optical Imaging/instrumentation/*methods ; *Quantum Dots/analysis/chemistry/toxicity ; Sulfides/chemistry ; Video Recording ; }, abstract = {With suppressed photon scattering and diminished autofluorescence, in vivo fluorescence imaging in the 1,500- to 1,700-nm range of the near-IR (NIR) spectrum (NIR-IIb window) can afford high clarity and deep tissue penetration. However, there has been a lack of NIR-IIb fluorescent probes with sufficient brightness and aqueous stability. Here, we present a bright fluorescent probe emitting at ∼1,600 nm based on core/shell lead sulfide/cadmium sulfide (CdS) quantum dots (CSQDs) synthesized in organic phase. The CdS shell plays a critical role of protecting the lead sulfide (PbS) core from oxidation and retaining its bright fluorescence through the process of amphiphilic polymer coating and transferring to water needed for imparting aqueous stability and compatibility. The resulting CSQDs with a branched PEG outer layer exhibited a long blood circulation half-life of 7 hours and enabled through-skin, real-time imaging of blood flows in mouse vasculatures at an unprecedented 60 frames per second (fps) speed by detecting ∼1,600-nm fluorescence under 808-nm excitation. It also allowed through-skin in vivo confocal 3D imaging of tumor vasculatures in mice with an imaging depth of ∼1.2 mm. The PEG-CSQDs accumulated in tumor effectively through the enhanced permeation and retention effect, affording a high tumor-to-normal tissue ratio up to ∼32 owing to the bright ∼1,600-nm emission and nearly zero autofluorescence background resulting from a large ∼800-nm Stoke's shift. The aqueous-compatible CSQDs are excreted through the biliary pathway without causing obvious toxicity effects, suggesting a useful class of ∼1,600-nm emitting probes for biomedical research.}, } @article {pmid29891701, year = {2018}, author = {Crowl, JT and Stetson, DB}, title = {SUMO2 and SUMO3 redundantly prevent a noncanonical type I interferon response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6798-6803}, pmid = {29891701}, issn = {1091-6490}, support = {K99 AI072945/AI/NIAID NIH HHS/United States ; R00 AI072945/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {HEK293 Cells ; Humans ; Interferon Regulatory Factor-3/genetics/metabolism ; Interferon Regulatory Factor-7/genetics/metabolism ; Interferon Type I/genetics/*metabolism ; Signal Transduction/*physiology ; Small Ubiquitin-Related Modifier Proteins/genetics/*metabolism ; Sumoylation/*physiology ; THP-1 Cells ; Ubiquitins/genetics/*metabolism ; }, abstract = {Detection of nucleic acids by innate immune sensors triggers the production of type I interferons (IFNs). While IFNs are essential for host defense against viral infection, dysregulated production of IFNs underlies numerous autoinflammatory diseases. We have found that the loss of sumoylation results in a potent, spontaneous IFN response. Vertebrates possess three small ubiquitin-like modifiers (SUMOs) that can be conjugated onto target proteins and alter protein function in diverse but still poorly characterized ways. We demonstrate that regulation of IFN by sumoylation is redundantly mediated by both SUMO2 and SUMO3, but not SUMO1, revealing a previously unknown function of SUMO2/3. Remarkably, this IFN response is independent of all known IFN-inducing pathways and does not require either of the canonical IFN-associated transcription factors IRF3 or IRF7. Taken together, our findings demonstrate that SUMO2 and SUMO3 are specific and essential negative regulators of a noncanonical mechanism of IFN induction.}, } @article {pmid29891700, year = {2018}, author = {Popov, S and Popova, E and Inoue, M and Wu, Y and Göttlinger, H}, title = {HIV-1 gag recruits PACSIN2 to promote virus spreading.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7093-7098}, pmid = {29891700}, issn = {1091-6490}, support = {DP1 DA038034/DA/NIDA NIH HHS/United States ; R01 AI029873/AI/NIAID NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/genetics/metabolism ; Adaptor Proteins, Signal Transducing/genetics/*metabolism ; Cell Line, Tumor ; Endosomal Sorting Complexes Required for Transport/genetics/metabolism ; HIV Infections/genetics/*metabolism/pathology/*transmission ; HIV-1/*physiology ; Humans ; Mutation ; Protein Domains ; Repressor Proteins/genetics/metabolism ; Ubiquitin-Protein Ligases/genetics/metabolism ; Virus Replication/*physiology ; gag Gene Products, Human Immunodeficiency Virus/genetics/*metabolism ; src Homology Domains ; }, abstract = {The p2b domain of Rous sarcoma virus (RSV) Gag and the p6 domain of HIV-1 Gag contain late assembly (L) domains that engage the ESCRT membrane fission machinery and are essential for virus release. We now show that the PPXY-type RSV L domain specifically recruits the BAR domain protein PACSIN2 into virus-like particles (VLP), in addition to the NEDD4-like ubiquitin ligase ITCH and ESCRT pathway components such as TSG101. PACSIN2, which has been implicated in the remodeling of cellular membranes and the actin cytoskeleton, is also recruited by HIV-1 p6 independent of its ability to engage the ESCRT factors TSG101 or ALIX. Moreover, PACSIN2 is robustly recruited by NEDD4-2s, a NEDD4-like ubiquitin ligase capable of rescuing HIV-1 budding defects. The NEDD4-2s-induced incorporation of PACSIN2 into VLP correlated with the formation of Gag-ubiquitin conjugates, indicating that PACSIN2 binds ubiquitin. Although PACSIN2 was not required for a single cycle of HIV-1 replication after infection with cell-free virus, HIV-1 spreading was nevertheless severely impaired in T cell lines and primary human peripheral blood mononuclear cells depleted of PACSIN2. HIV-1 spreading could be restored by reintroduction of wild-type PACSIN2, but not of a SH3 domain mutant unable to interact with the actin polymerization regulators WASP and N-WASP. Overall, our observations indicate that PACSIN2 promotes the cell-to-cell spreading of HIV-1 by connecting Gag to the actin cytoskeleton.}, } @article {pmid29891699, year = {2018}, author = {Gordon, CP and Shirase, S and Yamamoto, K and Andersen, RA and Eisenstein, O and Copéret, C}, title = {NMR chemical shift analysis decodes olefin oligo- and polymerization activity of d0 group 4 metal complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5867-E5876}, pmid = {29891699}, issn = {1091-6490}, abstract = {d0 metal-alkyl complexes (M = Ti, Zr, and Hf) show specific activity and selectivity in olefin polymerization and oligomerization depending on their ligand set and charge. Here, we show by a combined experimental and computational study that the 13C NMR chemical shift tensors of the α-carbon of metal alkyls that undergo olefin insertion signal the presence of partial alkylidene character in the metal-carbon bond, which facilitates this reaction. The alkylidene character is traced back to the π-donating interaction of a filled orbital on the alkyl group with an empty low-lying metal d-orbital of appropriate symmetry. This molecular orbital picture establishes a connection between olefin insertion into a metal-alkyl bond and olefin metathesis and a close link between the Cossee-Arlmann and Green-Rooney polymerization mechanisms. The 13C NMR chemical shifts, the α-H agostic interaction, and the low activation barrier of ethylene insertion are, therefore, the results of the same orbital interactions, thus establishing chemical shift tensors as a descriptor for olefin insertion.}, } @article {pmid29891698, year = {2018}, author = {McNichol, J and Stryhanyuk, H and Sylva, SP and Thomas, F and Musat, N and Seewald, JS and Sievert, SM}, title = {Primary productivity below the seafloor at deep-sea hot springs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6756-6761}, pmid = {29891698}, issn = {1091-6490}, mesh = {Aquatic Organisms/*metabolism ; Biomass ; Campylobacter/metabolism ; Carbon/metabolism ; Ecosystem ; Hot Temperature ; *Hydrothermal Vents ; *Microbiota ; Oxygen/metabolism ; Pacific Ocean ; Pressure ; Ribotyping ; Seawater/chemistry ; }, abstract = {Below the seafloor at deep-sea hot springs, mixing of geothermal fluids with seawater supports a potentially vast microbial ecosystem. Although the identity of subseafloor microorganisms is largely known, their effect on deep-ocean biogeochemical cycles cannot be predicted without quantitative measurements of their metabolic rates and growth efficiency. Here, we report on incubations of subseafloor fluids under in situ conditions that quantitatively constrain subseafloor primary productivity, biomass standing stock, and turnover time. Single-cell-based activity measurements and 16S rRNA-gene analysis showed that Campylobacteria dominated carbon fixation and that oxygen concentration and temperature drove niche partitioning of closely related phylotypes. Our data reveal a very active subseafloor biosphere that fixes carbon at a rate of up to 321 μg C⋅L-1⋅d-1, turns over rapidly within tens of hours, rivals the productivity of chemosynthetic symbioses above the seafloor, and significantly influences deep-ocean biogeochemical cycling.}, } @article {pmid29891697, year = {2018}, author = {Ahmed, F}, title = {QnAs with Ewine F. van Dishoeck.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {28}, pages = {7166-7167}, doi = {10.1073/pnas.1808261115}, pmid = {29891697}, issn = {1091-6490}, } @article {pmid29891696, year = {2018}, author = {Winstel, V and Missiakas, D and Schneewind, O}, title = {Staphylococcus aureus targets the purine salvage pathway to kill phagocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6846-6851}, pmid = {29891696}, issn = {1091-6490}, support = {R01 AI038897/AI/NIAID NIH HHS/United States ; R01 AI052474/AI/NIAID NIH HHS/United States ; }, mesh = {Caspase 3/genetics/*metabolism ; Cell Death/genetics ; Deoxyadenosines/genetics/*metabolism ; Extracellular Traps/genetics/*metabolism/microbiology ; Humans ; Neutrophils/*metabolism/microbiology/pathology ; Staphylococcal Infections/genetics/*metabolism/pathology ; Staphylococcus aureus/genetics/*metabolism ; }, abstract = {Staphylococcus aureus colonizes large segments of the human population and causes invasive infections due to its ability to escape phagocytic clearance. During infection, staphylococcal nuclease and adenosine synthase A convert neutrophil extracellular traps to deoxyadenosine (dAdo), which kills phagocytes. The mechanism whereby staphylococcal dAdo intoxicates phagocytes is not known. Here we used CRISPR-Cas9 mutagenesis to show that phagocyte intoxication involves uptake of dAdo via the human equilibrative nucleoside transporter 1, dAdo conversion to dAMP by deoxycytidine kinase and adenosine kinase, and signaling via subsequent dATP formation to activate caspase-3-induced cell death. Disruption of this signaling cascade confers resistance to dAdo-induced intoxication of phagocytes and may provide therapeutic opportunities for the treatment of infections caused by antibiotic-resistant S. aureus strains.}, } @article {pmid29891695, year = {2018}, author = {}, title = {Correction for Adam et al., Evolutionary history of carbon monoxide dehydrogenase/acetyl-CoA synthase, one of the oldest enzymatic complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5836-E5837}, doi = {10.1073/pnas.1807540115}, pmid = {29891695}, issn = {1091-6490}, } @article {pmid29891694, year = {2018}, author = {Priolo, C and Khabibullin, D and Reznik, E and Filippakis, H and Ogórek, B and Kavanagh, TR and Nijmeh, J and Herbert, ZT and Asara, JM and Kwiatkowski, DJ and Wu, CL and Henske, EP}, title = {Impairment of gamma-glutamyl transferase 1 activity in the metabolic pathogenesis of chromophobe renal cell carcinoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6274-E6282}, pmid = {29891694}, issn = {1091-6490}, support = {R01 CA216922/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/genetics/*metabolism ; Carcinoma, Renal Cell/*enzymology/genetics/pathology ; Female ; Humans ; Kidney Neoplasms/*enzymology/genetics/pathology ; Male ; Neoplasm Proteins/genetics/*metabolism ; Oligopeptides/genetics/*metabolism ; Oxidative Stress/genetics ; Signal Transduction/genetics ; gamma-Glutamyltransferase/genetics/*metabolism ; }, abstract = {Chromophobe renal cell carcinoma (ChRCC) accounts for 5% of all sporadic renal cancers and can also occur in genetic syndromes including Birt-Hogg-Dube (BHD) and tuberous sclerosis complex (TSC). ChRCC has a distinct accumulation of abnormal mitochondria, accompanied by characteristic chromosomal imbalances and relatively few "driver" mutations. Metabolomic profiling of ChRCC and oncocytomas (benign renal tumors that share pathological features with ChRCC) revealed both similarities and differences between these tumor types, with principal component analysis (PCA) showing a distinct separation. ChRCC have a striking decrease in intermediates of the glutathione salvage pathway (also known as the gamma-glutamyl cycle) compared with adjacent normal kidney, as well as significant changes in glycolytic and pentose phosphate pathway intermediates. We also found that gamma glutamyl transferase 1 (GGT1), the key enzyme of the gamma-glutamyl cycle, is expressed at ∼100-fold lower levels in ChRCC compared with normal kidney, while no change in GGT1 expression was found in clear cell RCC (ccRCC). Significant differences in specific metabolite abundance were found in ChRCC vs. ccRCC, including the oxidative stress marker ophthalmate. Down-regulation of GGT1 enhanced the sensitivity to oxidative stress and treatment with buthionine sulfoximine (BSO), which was associated with changes in glutathione-pathway metabolites. These data indicate that impairment of the glutathione salvage pathway, associated with enhanced oxidative stress, may have key therapeutic implications for this rare tumor type for which there are currently no specific targeted therapies.}, } @article {pmid29891693, year = {2018}, author = {Nidzieko, NJ}, title = {Allometric scaling of estuarine ecosystem metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6733-6738}, pmid = {29891693}, issn = {1091-6490}, mesh = {Animals ; Aquatic Organisms/*metabolism ; Autotrophic Processes ; *Carbon Cycle ; *Ecosystem ; *Estuaries ; Heterotrophic Processes ; United States ; Water/chemistry ; Water Movements ; }, abstract = {There are still significant uncertainties in the magnitude and direction of carbon fluxes through coastal ecosystems. An important component of these biogeochemical budgets is ecosystem metabolism, the net result of organismal metabolic processes within an ecosystem. In this paper, I present a synthesis of published ecosystem metabolism studies from coastal ecosystems and describe an empirical observation that size-dependent patterns in aquatic gross primary production and community respiration exist across a wide range of coastal geomorphologies. Ecosystem metabolism scales to the 3/4 power with volume in deeper estuaries dominated by pelagic primary production and nearly linearly with area in shallow estuaries dominated by benthic primary production. These results can be explained by applying scaling arguments for efficient, directed transport networks developed to explain similar size-dependent patterns in organismal metabolism. The main conclusion from this synthesis is that the residence time of new, nutrient-rich water is a fundamental organizing principle for the observed patterns. Residence time changes allometrically with size in pelagic ecosystems because velocities change by only an order of magnitude across systems that span more than ten orders of magnitude in size. This nonisometric change in velocity with size requires lower specific metabolic rates at larger ecosystem sizes. This change in transport may also explain a shift from predominantly net heterotrophy to net autotrophy with increasing size. The scaling results are applied to the total estuarine area in the continental United States to estimate the contribution of estuarine systems to the overall coastal budget of organic carbon.}, } @article {pmid29891692, year = {2018}, author = {Them, TR and Gill, BC and Caruthers, AH and Gerhardt, AM and Gröcke, DR and Lyons, TW and Marroquín, SM and Nielsen, SG and Trabucho Alexandre, JP and Owens, JD}, title = {Thallium isotopes reveal protracted anoxia during the Toarcian (Early Jurassic) associated with volcanism, carbon burial, and mass extinction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6596-6601}, pmid = {29891692}, issn = {1091-6490}, mesh = {Aquatic Organisms ; Atmosphere/*chemistry ; Canada ; Carbon/*analysis ; Climate Change/*history ; *Extinction, Biological ; Geologic Sediments/*chemistry ; Greenhouse Gases ; History, Ancient ; Isotopes/analysis ; Organic Chemicals/*chemistry ; *Oxygen ; Seawater/*chemistry ; Thallium/*analysis ; Thallium Radioisotopes/analysis ; Volcanic Eruptions/*history ; }, abstract = {For this study, we generated thallium (Tl) isotope records from two anoxic basins to track the earliest changes in global bottom water oxygen contents over the Toarcian Oceanic Anoxic Event (T-OAE; ∼183 Ma) of the Early Jurassic. The T-OAE, like other Mesozoic OAEs, has been interpreted as an expansion of marine oxygen depletion based on indirect methods such as organic-rich facies, carbon isotope excursions, and biological turnover. Our Tl isotope data, however, reveal explicit evidence for earlier global marine deoxygenation of ocean water, some 600 ka before the classically defined T-OAE. This antecedent deoxygenation occurs at the Pliensbachian/Toarcian boundary and is coeval with the onset of initial large igneous province (LIP) volcanism and the initiation of a marine mass extinction. Thallium isotopes are also perturbed during the T-OAE interval, as defined by carbon isotopes, reflecting a second deoxygenation event that coincides with the acme of elevated marine mass extinctions and the main phase of LIP volcanism. This suggests that the duration of widespread anoxic bottom waters was at least 1 million years in duration and spanned early to middle Toarcian time. Thus, the Tl data reveal a more nuanced record of marine oxygen depletion and its links to biological change during a period of climatic warming in Earth's past and highlight the role of oxygen depletion on past biological evolution.}, } @article {pmid29891691, year = {2018}, author = {Davidson, P and Penisson, C and Constantin, D and Gabriel, JP}, title = {Isotropic, nematic, and lamellar phases in colloidal suspensions of nanosheets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6662-6667}, pmid = {29891691}, issn = {1091-6490}, abstract = {The phase diagram of colloidal suspensions of electrically charged nanosheets, such as clays, despite their many industrial uses, is not yet understood either experimentally or theoretically. When the nanosheet diameter is very large (∼100 nm to 1 µm), it is quite challenging to distinguish the lamellar liquid-crystalline phase from a nematic phase with strong stacking local order, often called "columnar" nematic. We show here that newly upgraded small-angle X-ray scattering beamlines at synchrotron radiation facilities provide high-resolution measurements which allow us to identify both phases unambiguously, provided that single domains can be obtained. We investigated dilute aqueous suspensions of synthetic Sb3P2O143- nanosheets that self-organize into two distinct liquid-crystalline phases, sometimes coexisting in the same sample. Close examination of their X-ray reflection profiles in the directions perpendicular to the director demonstrates that these two mesophases are a columnar nematic and a lamellar phase. In the latter, the domain size reaches up to ∼20 µm, which means that each layer is made of >600 nanosheets. Because the lamellar phase was only rarely predicted in suspensions of charged disks, our results show that these systems should be revisited by theory or simulations. The unexpected stability of the lamellar phase also suggests that the rims and faces of Sb3P2O143- nanosheets may have different properties, giving them a patchy particle character.}, } @article {pmid29891690, year = {2018}, author = {Yan, J and Holzer, S and Pellegrini, L and Bell, SD}, title = {An archaeal primase functions as a nanoscale caliper to define primer length.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6697-6702}, pmid = {29891690}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 GM125579/GM/NIGMS NIH HHS/United States ; 104641/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adenosine Triphosphate/analogs & derivatives/metabolism ; Archaeal Proteins/*physiology ; Crystallography, X-Ray ; DNA Primase/chemistry/*physiology ; DNA Primers/*chemistry ; Fluorescence Polarization ; Models, Molecular ; Molecular Weight ; Protein Conformation ; Protein Subunits ; Sulfolobus solfataricus/*enzymology ; }, abstract = {The cellular replicative DNA polymerases cannot initiate DNA synthesis without a priming 3' OH. During DNA replication, this is supplied in the context of a short RNA primer molecule synthesized by DNA primase. The primase of archaea and eukaryotes, despite having varying subunit compositions, share sequence and structural homology. Intriguingly, archaeal primase has been demonstrated to possess the ability to synthesize DNA de novo, a property shared with the eukaryotic PrimPol enzymes. The dual RNA and DNA synthetic capabilities of the archaeal DNA primase have led to the proposal that there may be a sequential hand-off between these synthetic modes of primase. In the current work, we dissect the functional interplay between DNA and RNA synthetic modes of primase. In addition, we determine the key determinants that govern primer length definition by the archaeal primase. Our results indicate a primer measuring system that functions akin to a caliper.}, } @article {pmid29891689, year = {2018}, author = {Jin, H and Fu, M and Duan, Z and Duan, S and Li, M and Dong, X and Liu, B and Feng, D and Wang, J and Peng, L and Wang, HB}, title = {LOW PHOTOSYNTHETIC EFFICIENCY 1 is required for light-regulated photosystem II biogenesis in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6075-E6084}, pmid = {29891689}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/*biosynthesis/genetics/*metabolism ; Eukaryotic Initiation Factors/genetics/*metabolism ; *Gene Expression Regulation, Plant ; *Light ; Membrane Transport Proteins/genetics/*metabolism ; Photosystem II Protein Complex/*biosynthesis/genetics ; }, abstract = {Photosystem II (PSII), a multisubunit protein complex of the photosynthetic electron transport chain, functions as a water-plastoquinone oxidoreductase, which is vital to the initiation of photosynthesis and electron transport. Although the structure, composition, and function of PSII are well understood, the mechanism of PSII biogenesis remains largely elusive. Here, we identified a nuclear-encoded pentatricopeptide repeat (PPR) protein LOW PHOTOSYNTHETIC EFFICIENCY 1 (LPE1; encoded by At3g46610) in Arabidopsis, which plays a crucial role in PSII biogenesis. LPE1 is exclusively targeted to chloroplasts and directly binds to the 5' UTR of psbA mRNA which encodes the PSII reaction center protein D1. The loss of LPE1 results in less efficient loading of ribosome on the psbA mRNA and great synthesis defects in D1 protein. We further found that LPE1 interacts with a known regulator of psbA mRNA translation HIGH CHLOROPHYLL FLUORESCENCE 173 (HCF173) and facilitates the association of HCF173 with psbA mRNA. More interestingly, our results indicate that LPE1 associates with psbA mRNA in a light-dependent manner through a redox-based mechanism. This study enhances our understanding of the mechanism of light-regulated D1 synthesis, providing important insight into PSII biogenesis and the functional maintenance of efficient photosynthesis in higher plants.}, } @article {pmid29891688, year = {2018}, author = {Buntaine, MT and Jablonski, R and Nielson, DL and Pickering, PM}, title = {SMS texts on corruption help Ugandan voters hold elected councillors accountable at the polls.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6668-6673}, pmid = {29891688}, issn = {1091-6490}, mesh = {Budgets ; Disclosure ; Financial Management ; Government Employees ; Humans ; Persuasive Communication ; *Politics ; *Social Responsibility ; *Text Messaging ; *Truth Disclosure ; Uganda ; }, abstract = {Many politicians manipulate information to prevent voters from holding them accountable; however, mobile text messages may make it easier for nongovernmental organizations to credibly share information on official corruption that is difficult for politicians to counter directly. We test the potential for texts on budget management to improve democratic accountability by conducting a large (n = 16,083) randomized controlled trial during the 2016 Ugandan district elections. In cooperation with a local partner, we compiled, simplified, and text-messaged official information on irregularities in local government budgets. Verified recipients of messages that described more irregularities than expected reported voting for incumbent councillors 6% less often; verified recipients of messages conveying fewer irregularities than expected reported voting for incumbent councillors 5% more often. The messages had no observable effect on votes for incumbent council chairs, potentially due to voters' greater reliance on other sources of information for higher profile elections. These mixed results suggest that text messages on budget corruption help voters hold some politicians accountable in settings where elections are not free and fair.}, } @article {pmid29891687, year = {2018}, author = {Serbulea, V and Upchurch, CM and Schappe, MS and Voigt, P and DeWeese, DE and Desai, BN and Meher, AK and Leitinger, N}, title = {Macrophage phenotype and bioenergetics are controlled by oxidized phospholipids identified in lean and obese adipose tissue.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6254-E6263}, pmid = {29891687}, issn = {1091-6490}, support = {R01 DK096076/DK/NIDDK NIH HHS/United States ; P01 HL120840/HL/NHLBI NIH HHS/United States ; F31 DK108553/DK/NIDDK NIH HHS/United States ; T32 GM007055/GM/NIGMS NIH HHS/United States ; R01 GM108989/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adipose Tissue/metabolism/pathology ; Animals ; *Antigens, Differentiation/genetics/metabolism ; *Energy Metabolism ; *Macrophages/metabolism/pathology ; Mice ; Mice, Transgenic ; *Obesity/genetics/metabolism/pathology ; *Phospholipids/genetics/metabolism ; }, abstract = {Adipose tissue macrophages (ATMs) adapt their metabolic phenotype either to maintain lean tissue homeostasis or drive inflammation and insulin resistance in obesity. However, the factors in the adipose tissue microenvironment that control ATM phenotypic polarization and bioenergetics remain unknown. We have recently shown that oxidized phospholipids (OxPL) uniquely regulate gene expression and cellular metabolism in Mox macrophages, but the presence of the Mox phenotype in adipose tissue has not been reported. Here we show, using extracellular flux analysis, that ATMs isolated from lean mice are metabolically inhibited. We identify a unique population of CX3CR1neg/F4/80low ATMs that resemble the Mox (Txnrd1+HO1+) phenotype to be the predominant ATM phenotype in lean adipose tissue. In contrast, ATMs isolated from obese mice had characteristics typical of the M1/M2 (CD11c+CD206+) phenotype with highly activated bioenergetics. Quantifying individual OxPL species in the stromal vascular fraction of murine adipose tissue, using targeted liquid chromatography-mass spectrometry, revealed that high fat diet-induced adipose tissue expansion led to a disproportional increase in full-length over truncated OxPL species. In vitro studies showed that macrophages respond to truncated OxPL species by suppressing bioenergetics and up-regulating antioxidant programs, mimicking the Mox phenotype of ATMs isolated from lean mice. Conversely, full-length OxPL species induce proinflammatory gene expression and an activated bioenergetic profile that mimics ATMs isolated from obese mice. Together, these data identify a redox-regulatory Mox macrophage phenotype to be predominant in lean adipose tissue and demonstrate that individual OxPL species that accumulate in adipose tissue instruct ATMs to adapt their phenotype and bioenergetic profile to either maintain redox homeostasis or to promote inflammation.}, } @article {pmid29891686, year = {2018}, author = {Yang, L and Cheng, D and Xu, H and Zeng, X and Wan, X and Shui, J and Xiang, Z and Cao, D}, title = {Unveiling the high-activity origin of single-atom iron catalysts for oxygen reduction reaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6626-6631}, pmid = {29891686}, issn = {1091-6490}, abstract = {It is still a grand challenge to develop a highly efficient nonprecious-metal electrocatalyst to replace the Pt-based catalysts for oxygen reduction reaction (ORR). Here, we propose a surfactant-assisted method to synthesize single-atom iron catalysts (SA-Fe/NG). The half-wave potential of SA-Fe/NG is only 30 mV less than 20% Pt/C in acidic medium, while it is 30 mV superior to 20% Pt/C in alkaline medium. Moreover, SA-Fe/NG shows extremely high stability with only 12 mV and 15 mV negative shifts after 5,000 cycles in acidic and alkaline media, respectively. Impressively, the SA-Fe/NG-based acidic proton exchange membrane fuel cell (PEMFC) exhibits a high power density of 823 mW cm-2 Combining experimental results and density-functional theory (DFT) calculations, we further reveal that the origin of high-ORR activity of SA-Fe/NG is from the Fe-pyrrolic-N species, because such molecular incorporation is the key, leading to the active site increase in an order of magnitude which successfully clarifies the bottleneck puzzle of why a small amount of iron in the SA-Fe catalysts can exhibit extremely superior ORR activity.}, } @article {pmid29891685, year = {2018}, author = {Li, X and Das, A and Bi, D}, title = {Biological tissue-inspired tunable photonic fluid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6650-6655}, pmid = {29891685}, issn = {1091-6490}, mesh = {Cell Shape ; *Computer Simulation ; *Models, Theoretical ; *Nanoparticles ; *Optics and Photonics ; *Phase Transition ; Shear Strength ; Stress, Mechanical ; Transition Temperature ; }, abstract = {Inspired by how cells pack in dense biological tissues, we design 2D and 3D amorphous materials that possess a complete photonic bandgap. A physical parameter based on how cells adhere with one another and regulate their shapes can continuously tune the photonic bandgap size as well as the bulk mechanical properties of the material. The material can be tuned to go through a solid-fluid phase transition characterized by a vanishing shear modulus. Remarkably, the photonic bandgap persists in the fluid phase, giving rise to a photonic fluid that is robust to flow and rearrangements. Experimentally this design should lead to the engineering of self-assembled nonrigid photonic structures with photonic bandgaps that can be controlled in real time via mechanical and thermal tuning.}, } @article {pmid29891684, year = {2018}, author = {Kim, D and Han, H and Lee, JH and Choi, JW and Grossman, JC and Jang, HM and Kim, D}, title = {Electron-hole separation in ferroelectric oxides for efficient photovoltaic responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6566-6571}, pmid = {29891684}, issn = {1091-6490}, abstract = {Despite their potential to exceed the theoretical Shockley-Queisser limit, ferroelectric photovoltaics (FPVs) have performed inefficiently due to their extremely low photocurrents. Incorporating Bi2FeCrO6 (BFCO) as the light absorber in FPVs has recently led to impressively high and record photocurrents [Nechache R, et al. (2015) Nat Photonics 9:61-67], which has revived the FPV field. However, our understanding of this remarkable phenomenon is far from satisfactory. Here, we use first-principles calculations to determine that such excellent performance mainly lies in the efficient separation of electron-hole (e-h) pairs. We show that photoexcited electrons and holes in BFCO are spatially separated on the Fe and Cr sites, respectively. This separation is much more pronounced in disordered BFCO phases, which adequately explains the observed exceptional PV responses. We further establish a design strategy to discover next-generation FPV materials. By exploring 44 additional Bi-based double-perovskite oxides, we suggest five active-layer materials that offer a combination of strong e-h separations and visible-light absorptions for FPV applications. Our work indicates that charge separation is the most important issue to be addressed for FPVs to compete with conventional devices.}, } @article {pmid29891683, year = {2018}, author = {McKinlay, CJ and Benner, NL and Haabeth, OA and Waymouth, RM and Wender, PA}, title = {Enhanced mRNA delivery into lymphocytes enabled by lipid-varied libraries of charge-altering releasable transporters.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5859-E5866}, pmid = {29891683}, issn = {1091-6490}, support = {R37 CA031841/CA/NCI NIH HHS/United States ; R01 CA031845/CA/NCI NIH HHS/United States ; R01 CA031841/CA/NCI NIH HHS/United States ; S10 RR027431/RR/NCRR NIH HHS/United States ; R37 CA031845/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Carrier Proteins/chemistry/pharmacology ; *Gene Library ; Humans ; Jurkat Cells ; *Lipids/chemistry/pharmacology ; Lymphocytes/cytology/*metabolism ; Mice, Inbred BALB C ; *RNA, Messenger/chemistry/pharmacology ; Transfection/*methods ; }, abstract = {We report a strategy for generating a combinatorial library of oligonucleotide transporters with varied lipid domains and their use in the efficient transfection of lymphocytes with mRNA in vitro and in vivo. This library is based on amphiphilic charge-altering releasable transporters (CARTs) that contain a lipophilic block functionalized with various side-chain lipids and a polycationic α-amino ester mRNA-binding block that undergoes rearrangement to neutral small molecules, resulting in mRNA release. We show that certain binary mixtures of these lipid-varied CARTs provide up to a ninefold enhancement in mRNA translation in lymphocytes in vitro relative to either a single-lipid CART component alone or the commercial reagent Lipofectamine 2000, corresponding to a striking increase in percent transfection from 9-12% to 80%. Informed by the results with binary mixtures, we further show that CARTs consisting of optimized ratios of the two lead lipids incorporated into a single hybrid-lipid transporter molecule maintain the same delivery efficacy as the noncovalent mixture of two CARTs. The lead lipid CART mixtures and hybrid-lipid CARTs show enhanced lymphocyte transfection in primary T cells and in vivo in mice. This combinatorial approach for rapidly screening mRNA delivery vectors has provided lipid-varied CART mixtures and hybrid-lipid CARTs that exhibit significant improvement in mRNA delivery to lymphocytes, a finding of potentially broad value in research and clinical applications.}, } @article {pmid29891682, year = {2018}, author = {Sun, SY and Kaelber, JT and Chen, M and Dong, X and Nematbakhsh, Y and Shi, J and Dougherty, M and Lim, CT and Schmid, MF and Chiu, W and He, CY}, title = {Flagellum couples cell shape to motility in Trypanosoma brucei.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5916-E5925}, pmid = {29891682}, issn = {1091-6490}, support = {P41 GM103832/GM/NIGMS NIH HHS/United States ; R01 GM080139/GM/NIGMS NIH HHS/United States ; }, mesh = {Cryoelectron Microscopy ; *Cytoskeleton/metabolism/ultrastructure ; *Flagella/metabolism/ultrastructure ; *Trypanosoma brucei brucei/metabolism/ultrastructure ; }, abstract = {In the unicellular parasite Trypanosoma brucei, the causative agent of human African sleeping sickness, complex swimming behavior is driven by a flagellum laterally attached to the long and slender cell body. Using microfluidic assays, we demonstrated that T. brucei can penetrate through an orifice smaller than its maximum diameter. Efficient motility and penetration depend on active flagellar beating. To understand how active beating of the flagellum affects the cell body, we genetically engineered T. brucei to produce anucleate cytoplasts (zoids and minis) with different flagellar attachment configurations and different swimming behaviors. We used cryo-electron tomography (cryo-ET) to visualize zoids and minis vitrified in different motility states. We showed that flagellar wave patterns reflective of their motility states are coupled to cytoskeleton deformation. Based on these observations, we propose a mechanism for how flagellum beating can deform the cell body via a flexible connection between the flagellar axoneme and the cell body. This mechanism may be critical for T. brucei to disseminate in its host through size-limiting barriers.}, } @article {pmid29891681, year = {2018}, author = {Shen, E and Wang, Q and Rabe, H and Liu, W and Cantor, H and Leavenworth, JW}, title = {Chromatin remodeling by the NuRD complex regulates development of follicular helper and regulatory T cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6780-6785}, pmid = {29891681}, issn = {1091-6490}, support = {R01 AI037562/AI/NIAID NIH HHS/United States ; R01 AI048125/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Lineage ; *Chromatin Assembly and Disassembly ; Gene Expression Regulation/immunology/physiology ; Gene Knock-In Techniques ; Germinal Center/*cytology ; Lymphopoiesis/*physiology ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/*physiology ; Mice ; Mice, Knockout ; Neoplasm Proteins/physiology ; Osteopontin/biosynthesis/genetics ; Proto-Oncogene Proteins c-bcl-6/*physiology ; T-Lymphocytes, Helper-Inducer/*cytology ; T-Lymphocytes, Regulatory/*cytology ; Transcription, Genetic ; }, abstract = {Lineage commitment and differentiation into CD4+ T cell subsets reflect an interplay between chromatin regulators and transcription factors (TF). Follicular T cell development is regulated by the Bcl6 TF, which helps determine the phenotype and follicular localization of both CD4+ follicular helper T cells (TFH) and follicular regulatory T cells (TFR). Here we show that Bcl6-dependent control of follicular T cells is mediated by a complex formed between Bcl6 and the Mi-2β-nucleosome-remodeling deacetylase complex (Mi-2β-NuRD). Formation of this complex reflects the contribution of the intracellular isoform of osteopontin (OPN-i), which acts as a scaffold to stabilize binding between Bcl6 and the NuRD complex that together regulate the genetic program of both TFH and TFR cells. Defective assembly of the Bcl6-NuRD complex distorts follicular T cell differentiation, resulting in impaired TFR development and skewing of the TFH lineage toward a TH1-like program that includes expression of Blimp1, Tbet, granzyme B, and IFNγ. These findings define a core Bcl6-directed transcriptional complex that enables CD4+ follicular T cells to regulate the germinal center response.}, } @article {pmid29891680, year = {2018}, author = {Wu, J and Wu, H and An, J and Ballantyne, CM and Cyster, JG}, title = {Critical role of integrin CD11c in splenic dendritic cell capture of missing-self CD47 cells to induce adaptive immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6786-6791}, pmid = {29891680}, issn = {1091-6490}, support = {R01 HL098839/HL/NHLBI NIH HHS/United States ; R01 AI040098/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 AI045073/AI/NIAID NIH HHS/United States ; N01AI40098/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity/*physiology ; Animals ; CD11c Antigen/genetics/*immunology ; CD47 Antigen/*immunology ; Cell Proliferation/physiology ; Dendritic Cells/cytology/*immunology ; Mice ; Mice, Knockout ; Spleen/cytology/*immunology ; T-Lymphocytes/cytology/*immunology ; Talin/genetics/immunology ; }, abstract = {CD11c, also known as integrin alpha X, is the most widely used defining marker for dendritic cells (DCs). CD11c can bind complement iC3b and mediate phagocytosis in vitro, for which it is also referred to as complement receptor 4. However, the functions of this prominent marker protein in DCs, especially in vivo, remain poorly defined. Here, in the process of studying DC activation and immune responses induced by cells lacking self-CD47, we found that DC capture of CD47-deficient cells and DC activation was dependent on the integrin-signaling adaptor Talin1. Specifically, CD11c and its partner Itgb2 were required for DC capture of CD47-deficient cells. CD11b was not necessary for this process but could partially compensate in the absence of CD11c. Mice with DCs lacking Talin1, Itgb2, or CD11c were defective in supporting T-cell proliferation and differentiation induced by CD47-deficient cell associated antigen. These findings establish a critical role for CD11c in DC antigen uptake and activation in vivo. They may also contribute to understanding the functional mechanism of CD47-blockade therapies.}, } @article {pmid29891679, year = {2018}, author = {Yeung, E and van Veen, H and Vashisht, D and Sobral Paiva, AL and Hummel, M and Rankenberg, T and Steffens, B and Steffen-Heins, A and Sauter, M and de Vries, M and Schuurink, RC and Bazin, J and Bailey-Serres, J and Voesenek, LACJ and Sasidharan, R}, title = {A stress recovery signaling network for enhanced flooding tolerance in Arabidopsis thaliana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6085-E6094}, pmid = {29891679}, issn = {1091-6490}, mesh = {Abscisic Acid/genetics/metabolism ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Ethylenes/metabolism ; NADPH Oxidases/genetics/*metabolism ; Reactive Oxygen Species/*metabolism ; *Signal Transduction ; *Stress, Physiological ; }, abstract = {Abiotic stresses in plants are often transient, and the recovery phase following stress removal is critical. Flooding, a major abiotic stress that negatively impacts plant biodiversity and agriculture, is a sequential stress where tolerance is strongly dependent on viability underwater and during the postflooding period. Here we show that in Arabidopsis thaliana accessions (Bay-0 and Lp2-6), different rates of submergence recovery correlate with submergence tolerance and fecundity. A genome-wide assessment of ribosome-associated transcripts in Bay-0 and Lp2-6 revealed a signaling network regulating recovery processes. Differential recovery between the accessions was related to the activity of three genes: RESPIRATORY BURST OXIDASE HOMOLOG D, SENESCENCE-ASSOCIATED GENE113, and ORESARA1, which function in a regulatory network involving a reactive oxygen species (ROS) burst upon desubmergence and the hormones abscisic acid and ethylene. This regulatory module controls ROS homeostasis, stomatal aperture, and chlorophyll degradation during submergence recovery. This work uncovers a signaling network that regulates recovery processes following flooding to hasten the return to prestress homeostasis.}, } @article {pmid29891678, year = {2018}, author = {Ozawa, M and Berthier, L and Biroli, G and Rosso, A and Tarjus, G}, title = {Random critical point separates brittle and ductile yielding transitions in amorphous materials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6656-6661}, pmid = {29891678}, issn = {1091-6490}, abstract = {We combine an analytically solvable mean-field elasto-plastic model with molecular dynamics simulations of a generic glass former to demonstrate that, depending on their preparation protocol, amorphous materials can yield in two qualitatively distinct ways. We show that well-annealed systems yield in a discontinuous brittle way, as metallic and molecular glasses do. Yielding corresponds in this case to a first-order nonequilibrium phase transition. As the degree of annealing decreases, the first-order character becomes weaker and the transition terminates in a second-order critical point in the universality class of an Ising model in a random field. For even more poorly annealed systems, yielding becomes a smooth crossover, representative of the ductile rheological behavior generically observed in foams, emulsions, and colloidal glasses. Our results show that the variety of yielding behaviors found in amorphous materials does not necessarily result from the diversity of particle interactions or microscopic dynamics but is instead unified by carefully considering the role of the initial stability of the system.}, } @article {pmid29891677, year = {2018}, author = {Zhou, J and Li, C and Sachs, N and Chiu, MC and Wong, BH and Chu, H and Poon, VK and Wang, D and Zhao, X and Wen, L and Song, W and Yuan, S and Wong, KK and Chan, JF and To, KK and Chen, H and Clevers, H and Yuen, KY}, title = {Differentiated human airway organoids to assess infectivity of emerging influenza virus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6822-6827}, pmid = {29891677}, issn = {1091-6490}, mesh = {Humans ; Influenza A Virus, H1N1 Subtype/growth & development/*pathogenicity ; Influenza A Virus, H7N2 Subtype/growth & development/*pathogenicity ; *Influenza, Human ; Organoids/pathology/*virology ; Respiratory System/pathology/*virology ; }, abstract = {Novel reassortant avian influenza H7N9 virus and pandemic 2009 H1N1 (H1N1pdm) virus cause human infections, while avian H7N2 and swine H1N1 virus mainly infect birds and pigs, respectively. There is no robust in vitro model for assessing the infectivity of emerging viruses in humans. Based on a recently established method, we generated long-term expanding 3D human airway organoids which accommodate four types of airway epithelial cells: ciliated, goblet, club, and basal cells. We report differentiation conditions which increase ciliated cell numbers to a nearly physiological level with synchronously beating cilia readily discernible in every organoid. In addition, the differentiation conditions induce elevated levels of serine proteases, which are essential for productive infection of human influenza viruses and low-pathogenic avian influenza viruses. We also established improved 2D monolayer culture conditions for the differentiated airway organoids. To demonstrate the ability of differentiated airway organoids to identify human-infective virus, 3D and 2D differentiated airway organoids are applied to evaluate two pairs of viruses with known distinct infectivity in humans, H7N9/Ah versus H7N2 and H1N1pdm versus an H1N1 strain isolated from swine (H1N1sw). The human-infective H7N9/Ah virus replicated more robustly than the poorly human-infective H7N2 virus; the highly human-infective H1N1pdm virus replicated to a higher titer than the counterpart H1N1sw. Collectively, we developed differentiated human airway organoids which can morphologically and functionally simulate human airway epithelium. These differentiated airway organoids can be applied for rapid assessment of the infectivity of emerging respiratory viruses to human.}, } @article {pmid29891676, year = {2018}, author = {Xing, L and Anbarchian, T and Tsai, JM and Plant, GW and Nusse, R}, title = {Wnt/β-catenin signaling regulates ependymal cell development and adult homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5954-E5962}, pmid = {29891676}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Axin Protein/genetics/*metabolism ; *Cell Proliferation ; Mice ; Mice, Transgenic ; Neural Stem Cells/cytology/metabolism ; Neuroglia/cytology/*metabolism ; Spinal Cord/cytology/*growth & development ; Wnt Proteins/genetics/metabolism ; Wnt Signaling Pathway/*physiology ; beta Catenin/genetics/metabolism ; }, abstract = {In the adult mouse spinal cord, the ependymal cell population that surrounds the central canal is thought to be a promising source of quiescent stem cells to treat spinal cord injury. Relatively little is known about the cellular origin of ependymal cells during spinal cord development, or the molecular mechanisms that regulate ependymal cells during adult homeostasis. Using genetic lineage tracing based on the Wnt target gene Axin2, we have characterized Wnt-responsive cells during spinal cord development. Our results revealed that Wnt-responsive progenitor cells are restricted to the dorsal midline throughout spinal cord development, which gives rise to dorsal ependymal cells in a spatially restricted pattern. This is contrary to previous reports that suggested an exclusively ventral origin of ependymal cells, suggesting that ependymal cells may retain positional identities in relation to their neural progenitors. Our results further demonstrated that in the postnatal and adult spinal cord, all ependymal cells express the Wnt/β-catenin signaling target gene Axin2, as well as Wnt ligands. Genetic elimination of β-catenin or inhibition of Wnt secretion in Axin2-expressing ependymal cells in vivo both resulted in impaired proliferation, indicating that Wnt/β-catenin signaling promotes ependymal cell proliferation. These results demonstrate the continued importance of Wnt/β-catenin signaling for both ependymal cell formation and regulation. By uncovering the molecular signals underlying the formation and regulation of spinal cord ependymal cells, our findings thus enable further targeting and manipulation of this promising source of quiescent stem cells for therapeutic interventions.}, } @article {pmid29891675, year = {2018}, author = {Ishii, T and Hayakawa, H and Igawa, T and Sekiguchi, T and Sekiguchi, M}, title = {Specific binding of PCBP1 to heavily oxidized RNA to induce cell death.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6715-6720}, pmid = {29891675}, issn = {1091-6490}, mesh = {Amino Acid Substitution ; Apoptosis/*physiology ; CRISPR-Cas Systems ; Caspase 3/physiology ; Conserved Sequence ; Guanine/analogs & derivatives/metabolism ; HeLa Cells ; Heterogeneous-Nuclear Ribonucleoprotein D/metabolism ; Heterogeneous-Nuclear Ribonucleoproteins/chemistry/*metabolism ; Humans ; Hydrogen Peroxide/pharmacology ; Oxidation-Reduction ; Protein Domains ; RNA, Messenger/chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism ; Structure-Activity Relationship ; }, abstract = {In aerobically growing cells, the guanine base of RNA is oxidized to 8-oxo-7,8-dihydroguanine (8-oxoG), which induces alteration in their gene expression. We previously demonstrated that the human AUF1 protein binds to 8-oxoG in RNA to induce the selective degradation of oxidized messenger RNA. We herein report that the poly(C)-binding protein PCBP1 binds to more severely oxidized RNA to activate apoptosis-related reactions. While AUF1 binds to oligoribonucleotides carrying a single 8-oxoG, PCBP1 does not bind to such oligoribonucleotides but instead binds firmly to oligoribonucleotides in which two 8-oxoG residues are located nearby. PCBP1-deficient cells, constructed from the human HeLa S3 line using the CRISPR-Cas9 system, exhibited higher survival rates than HeLa S3 cells when small doses of hydrogen peroxide were applied. The levels of caspase-3 activation and PARP-1 cleavage in the PCBP1-deficient cells were significantly lower than those in wild-type cells. The structure-function relationship of PCBP1 was established with the use of PCBP1 mutant proteins in which the conserved KH domains were defective. Human cells appear to possess two distinct mechanisms, one controlled by AUF1 and the other by PCBP1, with the former functioning when messenger RNA is moderately oxidized and the latter operating when the RNA is more severely damaged.}, } @article {pmid29891674, year = {2018}, author = {Yang, J and Liu, Z and Wang, C and Yang, R and Rathkey, JK and Pinkard, OW and Shi, W and Chen, Y and Dubyak, GR and Abbott, DW and Xiao, TS}, title = {Mechanism of gasdermin D recognition by inflammatory caspases and their inhibition by a gasdermin D-derived peptide inhibitor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6792-6797}, pmid = {29891674}, issn = {1091-6490}, support = {P01 DK091222/DK/NIDDK NIH HHS/United States ; R21 AR069908/AR/NIAMS NIH HHS/United States ; P30 EB009998/EB/NIBIB NIH HHS/United States ; R01 GM086550/GM/NIGMS NIH HHS/United States ; R01 GM127609/GM/NIGMS NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis Regulatory Proteins/*chemistry/metabolism ; Caspase 3/chemistry/metabolism ; Caspase Inhibitors/*chemistry/metabolism ; Catalytic Domain ; HEK293 Cells ; Humans ; Jurkat Cells ; Mice ; Neoplasm Proteins/*chemistry/metabolism ; Peptides/*chemistry/metabolism ; Protein Structure, Secondary ; RAW 264.7 Cells ; THP-1 Cells ; }, abstract = {The inflammasomes are signaling platforms that promote the activation of inflammatory caspases such as caspases-1, -4, -5, and -11. Recent studies identified gasdermin D (GSDMD) as an effector for pyroptosis downstream of the inflammasome signaling pathways. Cleavage of GSDMD by inflammatory caspases allows its N-terminal domain to associate with membrane lipids and form pores that induce pyroptotic cell death. Despite the important role of GSDMD in pyroptosis, the molecular mechanisms of GSDMD recognition and cleavage by inflammatory caspases that trigger pyroptosis are poorly understood. Here, we demonstrate that the catalytic domains of inflammatory caspases can directly bind to both the full-length GSDMD and its cleavage site peptide, FLTD. A GSDMD-derived inhibitor, N-acetyl-Phe-Leu-Thr-Asp-chloromethylketone (Ac-FLTD-CMK), inhibits GSDMD cleavage by caspases-1, -4, -5, and -11 in vitro, suppresses pyroptosis downstream of both canonical and noncanonical inflammasomes, as well as reduces IL-1β release following activation of the NLRP3 inflammasome in macrophages. By contrast, the inhibitor does not target caspase-3 or apoptotic cell death, suggesting that Ac-FLTD-CMK is a specific inhibitor for inflammatory caspases. Crystal structure of caspase-1 in complex with Ac-FLTD-CMK reveals extensive enzyme-inhibitor interactions involving both hydrogen bonds and hydrophobic contacts. Comparison with other caspase-1 structures demonstrates drastic conformational changes at the four active-site loops that assemble the catalytic groove. The present study not only contributes to our understanding of GSDMD recognition by inflammatory caspases but also reports a specific inhibitor for these caspases that can serve as a tool for investigating inflammasome signaling.}, } @article {pmid29891673, year = {2018}, author = {Zheng, S and Sham, LT and Rubino, FA and Brock, KP and Robins, WP and Mekalanos, JJ and Marks, DS and Bernhardt, TG and Kruse, AC}, title = {Structure and mutagenic analysis of the lipid II flippase MurJ from Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6709-6714}, pmid = {29891673}, issn = {1091-6490}, support = {R01 GM106303/GM/NIGMS NIH HHS/United States ; T32 AI007061/AI/NIAID NIH HHS/United States ; R01 GM066174/GM/NIGMS NIH HHS/United States ; R01 GM076710/GM/NIGMS NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, mesh = {Crystallography, X-Ray ; Escherichia coli Proteins/*chemistry/genetics ; Evolution, Molecular ; Gene Library ; Gram-Negative Anaerobic Straight, Curved, and Helical Rods/enzymology ; High-Throughput Nucleotide Sequencing ; Models, Molecular ; Mutation ; Phospholipid Transfer Proteins/*chemistry/genetics ; Protein Conformation ; Recombinant Fusion Proteins/chemistry ; Structure-Activity Relationship ; }, abstract = {The peptidoglycan cell wall provides an essential protective barrier in almost all bacteria, defining cellular morphology and conferring resistance to osmotic stress and other environmental hazards. The precursor to peptidoglycan, lipid II, is assembled on the inner leaflet of the plasma membrane. However, peptidoglycan polymerization occurs on the outer face of the plasma membrane, and lipid II must be flipped across the membrane by the MurJ protein before its use in peptidoglycan synthesis. Due to its central role in cell wall assembly, MurJ is of fundamental importance in microbial cell biology and is a prime target for novel antibiotic development. However, relatively little is known regarding the mechanisms of MurJ function, and structural data for MurJ are available only from the extremophile Thermosipho africanus Here, we report the crystal structure of substrate-free MurJ from the gram-negative model organism Escherichia coli, revealing an inward-open conformation. Taking advantage of the genetic tractability of E. coli, we performed high-throughput mutagenesis and next-generation sequencing to assess mutational tolerance at every amino acid in the protein, providing a detailed functional and structural map for the enzyme and identifying sites for inhibitor development. Lastly, through the use of sequence coevolution analysis, we identify functionally important interactions in the outward-open state of the protein, supporting a rocker-switch model for lipid II transport.}, } @article {pmid29891672, year = {2018}, author = {Navarro, HI and Goldstein, AS}, title = {HoxB13 mediates AR-V7 activity in prostate cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6528-6529}, pmid = {29891672}, issn = {1091-6490}, support = {P50 CA092131/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; Homeodomain Proteins ; Humans ; Male ; *Prostatic Neoplasms ; Prostatic Neoplasms, Castration-Resistant ; *Receptors, Androgen ; }, } @article {pmid29891671, year = {2018}, author = {Sajfutdinow, M and Jacobs, WM and Reinhardt, A and Schneider, C and Smith, DM}, title = {Direct observation and rational design of nucleation behavior in addressable self-assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5877-E5886}, pmid = {29891671}, issn = {1091-6490}, support = {F32 GM116231/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA/*chemistry ; *Light ; *Models, Chemical ; *Scattering, Radiation ; }, abstract = {To optimize a self-assembly reaction, it is essential to understand the factors that govern its pathway. Here, we examine the influence of nucleation pathways in a model system for addressable, multicomponent self-assembly based on a prototypical "DNA-brick" structure. By combining temperature-dependent dynamic light scattering and atomic force microscopy with coarse-grained simulations, we show how subtle changes in the nucleation pathway profoundly affect the yield of the correctly formed structures. In particular, we can increase the range of conditions over which self-assembly occurs by using stable multisubunit clusters that lower the nucleation barrier for assembling subunits in the interior of the structure. Consequently, modifying only a small portion of a structure is sufficient to optimize its assembly. Due to the generality of our coarse-grained model and the excellent agreement that we find with our experimental results, the design principles reported here are likely to apply generically to addressable, multicomponent self-assembly.}, } @article {pmid29891670, year = {2018}, author = {Wollman, I and Penhune, V and Segado, M and Carpentier, T and Zatorre, RJ}, title = {Neural network retuning and neural predictors of learning success associated with cello training.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6056-E6064}, pmid = {29891670}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Adult ; Auditory Cortex/diagnostic imaging/*physiology ; Female ; Humans ; Learning/*physiology ; Magnetic Resonance Imaging ; Male ; Motor Cortex/diagnostic imaging/*physiology ; *Music ; Nerve Net/diagnostic imaging/*physiology ; }, abstract = {The auditory and motor neural systems are closely intertwined, enabling people to carry out tasks such as playing a musical instrument whose mapping between action and sound is extremely sophisticated. While the dorsal auditory stream has been shown to mediate these audio-motor transformations, little is known about how such mapping emerges with training. Here, we use longitudinal training on a cello as a model for brain plasticity during the acquisition of specific complex skills, including continuous and many-to-one audio-motor mapping, and we investigate individual differences in learning. We trained participants with no musical background to play on a specially designed MRI-compatible cello and scanned them before and after 1 and 4 wk of training. Activation of the auditory-to-motor dorsal cortical stream emerged rapidly during the training and was similarly activated during passive listening and cello performance of trained melodies. This network activation was independent of performance accuracy and therefore appears to be a prerequisite of music playing. In contrast, greater recruitment of regions involved in auditory encoding and motor control over the training was related to better musical proficiency. Additionally, pre-supplementary motor area activity and its connectivity with the auditory cortex during passive listening before training was predictive of final training success, revealing the integrative function of this network in auditory-motor information processing. Together, these results clarify the critical role of the dorsal stream and its interaction with auditory areas in complex audio-motor learning.}, } @article {pmid29891669, year = {2018}, author = {Melnikoff, DE and Bailey, AH}, title = {Reply to Landy et al.: Terms and conditions may apply.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5637-E5638}, pmid = {29891669}, issn = {1091-6490}, mesh = {*Morals ; }, } @article {pmid29891668, year = {2018}, author = {Ravindran, S}, title = {QnAs with John E. Cronan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {6878-6879}, pmid = {29891668}, issn = {1091-6490}, mesh = {Animals ; Biochemistry/*history ; Biotin/*metabolism ; History, 20th Century ; History, 21st Century ; Humans ; *Lipid Metabolism ; Portraits as Topic ; Thioctic Acid/*metabolism ; }, } @article {pmid29891667, year = {2018}, author = {}, title = {Correction for Oyen et al., Structural basis for antibody recognition of the NANP repeats in Plasmodium falciparum circumsporozoite protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5838-E5839}, doi = {10.1073/pnas.1808460115}, pmid = {29891667}, issn = {1091-6490}, } @article {pmid29891666, year = {2018}, author = {}, title = {Editorial Expression of Concern: Endurance exercise rescues progeroid aging and induces systemic mitochondrial rejuvenation in mtDNA mutator mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5834}, doi = {10.1073/pnas.1808586115}, pmid = {29891666}, issn = {1091-6490}, } @article {pmid29891665, year = {2018}, author = {Wilczewski, CM and Hepperla, AJ and Shimbo, T and Wasson, L and Robbe, ZL and Davis, IJ and Wade, PA and Conlon, FL}, title = {CHD4 and the NuRD complex directly control cardiac sarcomere formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6727-6732}, pmid = {29891665}, issn = {1091-6490}, support = {Z01 ES101965/ES/NIEHS NIH HHS/United States ; F31 HL136100/HL/NHLBI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 HL127640/HL/NHLBI NIH HHS/United States ; R01 HL112618/HL/NHLBI NIH HHS/United States ; T32 HL069768/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; DNA Helicases/chemistry/deficiency/*physiology ; Female ; *Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Genes, Lethal ; Heart/diagnostic imaging/embryology ; Heart Defects, Congenital/diagnostic imaging/embryology/*genetics/pathology ; Male ; Mi-2 Nucleosome Remodeling and Deacetylase Complex/*physiology ; Mice ; Muscle Proteins/biosynthesis/genetics ; Myocytes, Cardiac/*physiology ; Myofibrils/metabolism/pathology ; Nucleosomes/metabolism/ultrastructure ; Sarcomeres/*physiology/ultrastructure ; Transcription, Genetic ; Ultrasonography, Prenatal ; }, abstract = {Cardiac development relies on proper cardiomyocyte differentiation, including expression and assembly of cell-type-specific actomyosin subunits into a functional cardiac sarcomere. Control of this process involves not only promoting expression of cardiac sarcomere subunits but also repressing expression of noncardiac myofibril paralogs. This level of transcriptional control requires broadly expressed multiprotein machines that modify and remodel the chromatin landscape to restrict transcription machinery access. Prominent among these is the nucleosome remodeling and deacetylase (NuRD) complex, which includes the catalytic core subunit CHD4. Here, we demonstrate that direct CHD4-mediated repression of skeletal and smooth muscle myofibril isoforms is required for normal cardiac sarcomere formation, function, and embryonic survival early in gestation. Through transcriptomic and genome-wide analyses of CHD4 localization, we identified unique CHD4 binding sites in smooth muscle myosin heavy chain, fast skeletal α-actin, and the fast skeletal troponin complex genes. We further demonstrate that in the absence of CHD4, cardiomyocytes in the developing heart form a hybrid muscle cell that contains cardiac, skeletal, and smooth muscle myofibril components. These misexpressed paralogs intercalate into the nascent cardiac sarcomere to disrupt sarcomere formation and cause impaired cardiac function in utero. These results demonstrate the genomic and physiological requirements for CHD4 in mammalian cardiac development.}, } @article {pmid29891664, year = {2018}, author = {Li, X and Guo, T and Mu, Q and Li, X and Yu, J}, title = {Genomic and environmental determinants and their interplay underlying phenotypic plasticity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6679-6684}, pmid = {29891664}, issn = {1091-6490}, mesh = {Epistasis, Genetic ; Flowers/growth & development ; *Gene-Environment Interaction ; Genetic Association Studies ; Inbreeding ; Midwestern United States ; *Phenotype ; Photoperiod ; Plant Breeding ; Polymorphism, Single Nucleotide ; Puerto Rico ; Seasons ; Sorghum/*genetics/growth & development ; Temperature ; }, abstract = {Observed phenotypic variation in living organisms is shaped by genomes, environment, and their interactions. Flowering time under natural conditions can showcase the diverse outcome of the gene-environment interplay. However, identifying hidden patterns and specific factors underlying phenotypic plasticity under natural field conditions remains challenging. With a genetic population showing dynamic changes in flowering time, here we show that the integrated analyses of genomic responses to diverse environments is powerful to reveal the underlying genetic architecture. Specifically, the effect continuum of individual genes (Ma1 , Ma6 , FT, and ELF3) was found to vary in size and in direction along an environmental gradient that was quantified by photothermal time, a combination of two environmental factors (photoperiod and temperature). Gene-gene interaction was also contributing to the observed phenotypic plasticity. With the identified environmental index to quantitatively connect environments, a systematic genome-wide performance prediction framework was established through either genotype-specific reaction-norm parameters or genome-wide marker-effect continua. These parallel genome-wide approaches were demonstrated for in-season and on-target performance prediction by simultaneously exploiting genomics, environment profiling, and performance information. Improved understanding of mechanisms for phenotypic plasticity enables a concerted exploration that turns challenge into opportunity.}, } @article {pmid29891663, year = {2018}, author = {Smith, NM and Ebrahimi, H and Ghosh, R and Dickerson, AK}, title = {High-speed microjets issue from bursting oil gland reservoirs of citrus fruit.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5887-E5895}, pmid = {29891663}, issn = {1091-6490}, mesh = {Citrus/*chemistry ; Fruit/*chemistry ; Plant Oils/*chemistry ; }, abstract = {The rupture of oil gland reservoirs housed near the outer surface of the citrus exocarp is a common experience to the discerning citrus consumer and bartenders the world over. These reservoirs often rupture outwardly in response to bending the peel, which compresses the soft material surrounding the reservoirs, the albedo, increasing fluid pressure in the reservoir. Ultimately, fluid pressure exceeds the failure strength of the outermost membrane, the flavedo. The ensuing high-velocity discharge of oil and exhaustive emptying of oil gland reservoirs creates a method for jetting small quantities of the aromatic oil. We compare this jetting behavior across five citrus hybrids through high-speed videography. The jetting oil undergoes an extreme acceleration to reach velocities in excess of 10 m/s. Through material characterization and finite element simulations, we rationalize the combination of tuned material properties and geometries enabling the internal reservoir pressures that produce explosive dispersal, finding the composite structure of the citrus peel is critical for microjet production.}, } @article {pmid29891662, year = {2018}, author = {Tang, YA and Chen, YF and Bao, Y and Mahara, S and Yatim, SMJM and Oguz, G and Lee, PL and Feng, M and Cai, Y and Tan, EY and Fong, SS and Yang, ZH and Lan, P and Wu, XJ and Yu, Q}, title = {Hypoxic tumor microenvironment activates GLI2 via HIF-1α and TGF-β2 to promote chemoresistance in colorectal cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5990-E5999}, pmid = {29891662}, issn = {1091-6490}, mesh = {Cell Hypoxia ; Colorectal Neoplasms/drug therapy/genetics/*metabolism/pathology ; *Drug Resistance, Neoplasm ; Female ; Fibroblasts/metabolism/pathology ; *Gene Expression Regulation, Neoplastic ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/*biosynthesis/genetics ; Male ; Neoplasm Proteins/*biosynthesis/genetics ; Nuclear Proteins/*biosynthesis/genetics ; Transforming Growth Factor beta2/*biosynthesis/genetics ; *Tumor Microenvironment ; Zinc Finger Protein Gli2/*biosynthesis/genetics ; }, abstract = {Colorectal cancer patients often relapse after chemotherapy, owing to the survival of stem or progenitor cells referred to as cancer stem cells (CSCs). Although tumor stromal factors are known to contribute to chemoresistance, it remains not fully understood how CSCs in the hypoxic tumor microenvironment escape the chemotherapy. Here, we report that hypoxia-inducible factor (HIF-1α) and cancer-associated fibroblasts (CAFs)-secreted TGF-β2 converge to activate the expression of hedgehog transcription factor GLI2 in CSCs, resulting in increased stemness/dedifferentiation and intrinsic resistance to chemotherapy. Genetic or small-molecule inhibitor-based ablation of HIF-1α/TGF-β2-mediated GLI2 signaling effectively reversed the chemoresistance caused by the tumor microenvironment. Importantly, high expression levels of HIF-1α/TGF-β2/GLI2 correlated robustly with the patient relapse following chemotherapy, highlighting a potential biomarker and therapeutic target for chemoresistance in colorectal cancer. Our study thus uncovers a molecular mechanism by which hypoxic colorectal tumor microenvironment promotes cancer cell stemness and resistance to chemotherapy and suggests a potentially targeted treatment approach to mitigating chemoresistance.}, } @article {pmid29891661, year = {2018}, author = {}, title = {Correction for Zahran et al., Assessment of the Legionnaires' disease outbreak in Flint, Michigan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5835}, doi = {10.1073/pnas.1808389115}, pmid = {29891661}, issn = {1091-6490}, } @article {pmid29891660, year = {2018}, author = {Bratsberg, B and Rogeberg, O}, title = {Flynn effect and its reversal are both environmentally caused.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6674-6678}, pmid = {29891660}, issn = {1091-6490}, mesh = {Adult ; Birth Order ; Cohort Studies ; Educational Status ; Emigrants and Immigrants/psychology ; Family Characteristics ; Fertility ; Humans ; *Intelligence/genetics ; Male ; Middle Aged ; Military Personnel/psychology ; *Models, Genetic ; Norway ; Nutritional Status ; Siblings/psychology ; *Social Environment ; }, abstract = {Population intelligence quotients increased throughout the 20th century-a phenomenon known as the Flynn effect-although recent years have seen a slowdown or reversal of this trend in several countries. To distinguish between the large set of proposed explanations, we categorize hypothesized causal factors by whether they accommodate the existence of within-family Flynn effects. Using administrative register data and cognitive ability scores from military conscription data covering three decades of Norwegian birth cohorts (1962-1991), we show that the observed Flynn effect, its turning point, and subsequent decline can all be fully recovered from within-family variation. The analysis controls for all factors shared by siblings and finds no evidence for prominent causal hypotheses of the decline implicating genes and environmental factors that vary between, but not within, families.}, } @article {pmid29891659, year = {2018}, author = {Scheelbeek, PFD and Bird, FA and Tuomisto, HL and Green, R and Harris, FB and Joy, EJM and Chalabi, Z and Allen, E and Haines, A and Dangour, AD}, title = {Effect of environmental changes on vegetable and legume yields and nutritional quality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6804-6809}, pmid = {29891659}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 106924/Z/15/Z//Wellcome Trust/United Kingdom ; 205200/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Carbon Dioxide/*metabolism ; *Climate Change ; Fabaceae/*growth & development ; *Nutritive Value ; Ozone/*metabolism ; Vegetables/*growth & development ; }, abstract = {Environmental changes threaten agricultural production, food security, and health. Previous reviews suggest that environmental changes will substantially affect future yields of starchy dietary staples. To date, no comprehensive global analysis of the impacts of environmental change on (nonstaple) vegetables and legumes-important constituents of healthy diets-has been reported. We systematically searched for articles published between 1975 and 2016 on the effects of ambient temperature, tropospheric carbon dioxide (CO2), and ozone (O3) concentrations, water availability, and salinization on yields and nutritional quality of vegetables and legumes. We estimated mean effects of standardized environmental changes using observed exposure-response relationships and conducted meta-analyses where possible. We identified 174 relevant papers reporting 1,540 experiments. The mean (95% CI) reported yield changes for all vegetables and legumes combined were +22.0% (+11.6% to +32.5%) for a 250-ppm increase in CO2 concentration, -8.9% (-15.6% to -2.2%) for a 25% increase in O3 concentration,-34.7% (-44.6% to -24.9%) for a 50% reduction in water availability, and -2.3% (-3.7% to -0.9%) for a 25% increase in salinity. In papers with baseline temperatures >20 °C, a 4 °C increase in temperature reduced mean yields by -31.5% (-41.4% to -21.5%). Impacts of environmental changes on nutritional quality were mixed. In a business-as-usual scenario, predicted changes in environmental exposures would lead to reductions in yields of nonstaple vegetables and legumes. Where adaptation possibilities are limited, this may substantially change their global availability, affordability, and consumption in the mid to long term. Our results stress the importance of prioritizing agricultural developments, to minimize potential reductions in vegetable and legume yields and associated negative health effects.}, } @article {pmid29891658, year = {2018}, author = {Choudhury, S and Vu, D and Warren, A and Tikekar, MD and Tu, Z and Archer, LA}, title = {Confining electrodeposition of metals in structured electrolytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6620-6625}, pmid = {29891658}, issn = {1091-6490}, abstract = {Electrochemical cells based on alkali metal (Li, Na) anodes have attracted significant recent attention because of their promise for producing large increases in gravimetric energy density for energy storage in batteries. To facilitate stable, long-term operation of such cells a variety of structured electrolytes have been designed in different physical forms, ranging from soft polymer gels to hard ceramics, including nanoporous versions of these ceramics that host a liquid or molten polymer in their pores. In almost every case, the electrolytes are reported to be substantially more effective than anticipated by early theories in improving uniformity of deposition and lifetime of the metal anode. These observations have been speculated to reflect the effect of electrolyte structure in regulating ion transport to the metal electrolyte interface, thereby stabilizing metal electrodeposition processes at the anode. Here we create and study model structured electrolytes composed of covalently linked polymer grafted nanoparticles that host a liquid electrolyte in the pores. The electrolytes exist as freestanding membranes with effective pore size that can be systematically manipulated through straightforward control of the volume fraction of the nanoparticles. By means of physical analysis and direct visualization experiments we report that at current densities approaching the diffusion limit, there is a clear transition from unstable to stable electrodeposition at Li metal electrodes in membranes with average pore sizes below 500 nm. We show that this transition is consistent with expectations from a recent theoretical analysis that takes into account local coupling between stress and ion transport at metal-electrolyte interfaces.}, } @article {pmid29891657, year = {2018}, author = {Mosbahi, K and Wojnowska, M and Albalat, A and Walker, D}, title = {Bacterial iron acquisition mediated by outer membrane translocation and cleavage of a host protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6840-6845}, pmid = {29891657}, issn = {1091-6490}, support = {BB/L02022X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Cell Membrane/genetics/*metabolism ; Iron/*metabolism ; Membrane Proteins/genetics/*metabolism ; Pectobacterium/genetics/*metabolism ; Peptide Elongation Factor G/genetics/*metabolism ; Periplasm/genetics/metabolism ; *Proteolysis ; }, abstract = {Iron is an essential micronutrient for most bacteria and is obtained from iron-chelating siderophores or directly from iron-containing host proteins. For Gram-negative bacteria, classical iron transport systems consist of an outer membrane receptor, a periplasmic binding protein, and an inner membrane ABC transporter, which work in concert to deliver iron from the cell surface to the cytoplasm. We recently showed that Pectobacterium spp. are able to acquire iron from ferredoxin, a small and stable 2Fe-2S iron sulfur cluster containing protein and identified the ferredoxin receptor, FusA, a TonB-dependent receptor that binds ferredoxin on the cell surface. The genetic context of fusA suggests an atypical iron acquisition system, lacking a periplasmic binding protein, although the mechanism through which iron is extracted from the captured ferredoxin has remained unknown. Here we show that FusC, an M16 family protease, displays a highly targeted proteolytic activity against plant ferredoxin, and that growth enhancement of Pectobacterium due to iron acquisition from ferredoxin is FusC-dependent. The periplasmic location of FusC indicates a mechanism in which ferredoxin is imported into the periplasm via FusA before cleavage by FusC, as confirmed by the uptake and accumulation of ferredoxin in the periplasm in a strain lacking fusC The existence of homologous uptake systems in a range of pathogenic bacteria suggests that protein uptake for nutrient acquisition may be widespread in bacteria and shows that, similar to their endosymbiotic descendants mitochondria and chloroplasts, bacteria produce dedicated protein import systems.}, } @article {pmid29891656, year = {2018}, author = {Severin, GB and Ramliden, MS and Hawver, LA and Wang, K and Pell, ME and Kieninger, AK and Khataokar, A and O'Hara, BJ and Behrmann, LV and Neiditch, MB and Benning, C and Waters, CM and Ng, WL}, title = {Direct activation of a phospholipase by cyclic GMP-AMP in El Tor Vibrio cholerae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6048-E6055}, pmid = {29891656}, issn = {1091-6490}, support = {T32 GM007310/GM/NIGMS NIH HHS/United States ; R01 GM110444/GM/NIGMS NIH HHS/United States ; R03 AI130554/AI/NIAID NIH HHS/United States ; R01 GM109259/GM/NIGMS NIH HHS/United States ; R01 AI125452/AI/NIAID NIH HHS/United States ; R01 AI121337/AI/NIAID NIH HHS/United States ; T32 AI007329/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Cell Membrane/*enzymology/genetics ; Nucleotides, Cyclic/genetics/*metabolism ; Phospholipases/genetics/*metabolism ; Second Messenger Systems/*physiology ; Vibrio cholerae/*enzymology/genetics ; }, abstract = {Sensing and responding to environmental changes is essential for bacteria to adapt and thrive, and nucleotide-derived second messengers are central signaling systems in this process. The most recently identified bacterial cyclic dinucleotide second messenger, 3', 3'-cyclic GMP-AMP (cGAMP), was first discovered in the El Tor biotype of Vibrio cholerae The cGAMP synthase, DncV, is encoded on the VSP-1 pathogenicity island, which is found in all El Tor isolates that are responsible for the current seventh pandemic of cholera but not in the classical biotype. We determined that unregulated production of DncV inhibits growth in El Tor V. cholerae but has no effect on the classical biotype. This cGAMP-dependent phenotype can be suppressed by null mutations in vc0178 immediately 5' of dncV in VSP-1. VC0178 [renamed as cGAMP-activated phospholipase in Vibrio (CapV)] is predicted to be a patatin-like phospholipase, and coexpression of capV and dncV is sufficient to induce growth inhibition in classical V. cholerae and Escherichia coli Furthermore, cGAMP binds to CapV and directly activates its hydrolase activity in vitro. CapV activated by cGAMP in vivo degrades phospholipids in the cell membrane, releasing 16:1 and 18:1 free fatty acids. Together, we demonstrate that cGAMP activates CapV phospholipase activity to target the cell membrane and suggest that acquisition of this second messenger signaling pathway may contribute to the emergence of the El Tor biotype as the etiological agent behind the seventh cholera pandemic.}, } @article {pmid29891655, year = {2018}, author = {Zhu, Y and Cankova, Z and Iwanaszko, M and Lichtor, S and Mrksich, M and Ameer, GA}, title = {Potent laminin-inspired antioxidant regenerative dressing accelerates wound healing in diabetes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6816-6821}, pmid = {29891655}, issn = {1091-6490}, mesh = {Animals ; *Antioxidants/chemistry/pharmacology ; *Bandages ; Diabetes Mellitus, Experimental/metabolism/pathology/*therapy ; Diabetic Foot/metabolism/pathology/*therapy ; *Hydrogels/chemistry/pharmacology ; *Laminin/chemistry/pharmacology ; Mice ; *Oligopeptides/chemistry/pharmacology ; *Wound Healing ; }, abstract = {The successful treatment of chronic dermal wounds, such as diabetic foot ulcers (DFU), depends on the development of safe, effective, and affordable regenerative tools that the surgeon can rely on to promote wound closure. Although promising, strategies that involve cell-based therapies and the local release of exogenous growth factors are costly, require very long development times, and result in modest improvements in patient outcome. We describe the development of an antioxidant shape-conforming regenerative wound dressing that uses the laminin-derived dodecapeptide A5G81 as a potent tethered cell adhesion-, proliferation-, and haptokinesis-inducing ligand to locally promote wound closure. A5G81 immobilized within a thermoresponsive citrate-based hydrogel facilitates integrin-mediated spreading, migration, and proliferation of dermal and epidermal cells, resulting in faster tissue regeneration in diabetic wounds. This peptide-hydrogel system represents a paradigm shift in dermoconductive and dermoinductive strategies for treating DFU without the need for soluble biological or pharmacological factors.}, } @article {pmid29891654, year = {2018}, author = {Matsuura, Y and Moriyama, M and Łukasik, P and Vanderpool, D and Tanahashi, M and Meng, XY and McCutcheon, JP and Fukatsu, T}, title = {Recurrent symbiont recruitment from fungal parasites in cicadas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5970-E5979}, pmid = {29891654}, issn = {1091-6490}, mesh = {Alphaproteobacteria/cytology/*metabolism ; Animals ; Ascomycota/cytology/*metabolism ; *Biological Evolution ; Flavobacteriaceae/cytology/*metabolism ; Hemiptera/*microbiology ; *Symbiosis ; }, abstract = {Diverse insects are associated with ancient bacterial symbionts, whose genomes have often suffered drastic reduction and degeneration. In extreme cases, such symbiont genomes seem almost unable to sustain the basic cellular functioning, which comprises an open question in the evolution of symbiosis. Here, we report an insect group wherein an ancient symbiont lineage suffering massive genome erosion has experienced recurrent extinction and replacement by host-associated pathogenic microbes. Cicadas are associated with the ancient bacterial co-obligate symbionts Sulcia and Hodgkinia, whose streamlined genomes are specialized for synthesizing essential amino acids, thereby enabling the host to live on plant sap. However, our inspection of 24 Japanese cicada species revealed that while all species possessed Sulcia, only nine species retained Hodgkinia, and their genomes exhibited substantial structural instability. The remaining 15 species lacked Hodgkinia and instead harbored yeast-like fungal symbionts. Detailed phylogenetic analyses uncovered repeated Hodgkinia-fungus and fungus-fungus replacements in cicadas. The fungal symbionts were phylogenetically intermingled with cicada-parasitizing Ophiocordyceps fungi, identifying entomopathogenic origins of the fungal symbionts. Most fungal symbionts of cicadas were uncultivable, but the fungal symbiont of Meimuna opalifera was cultivable, possibly because it is at an early stage of fungal symbiont replacement. Genome sequencing of the fungal symbiont revealed its metabolic versatility, presumably capable of synthesizing almost all amino acids, vitamins, and other metabolites, which is more than sufficient to compensate for the Hodgkinia loss. These findings highlight a straightforward ecological and evolutionary connection between parasitism and symbiosis, which may provide an evolutionary trajectory to renovate deteriorated ancient symbiosis via pathogen domestication.}, } @article {pmid29891653, year = {2018}, author = {Yang, Y and Qu, N and Tan, J and Rushdi, MN and Krueger, CJ and Chen, AK}, title = {Roles of Gag-RNA interactions in HIV-1 virus assembly deciphered by single-molecule localization microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6721-6726}, pmid = {29891653}, issn = {1091-6490}, mesh = {Animals ; COS Cells ; Cercopithecus aethiops ; Diffusion ; HIV-1/metabolism ; Nucleocapsid/metabolism ; Protein Binding ; Protein Domains ; Proviruses/metabolism ; RNA, Viral/*metabolism ; Recombinant Proteins/metabolism ; *Single Molecule Imaging ; Virus Assembly/*physiology ; gag Gene Products, Human Immunodeficiency Virus/*metabolism ; }, abstract = {During HIV-1 assembly, the retroviral structural protein Gag forms an immature capsid, containing thousands of Gag molecules, at the plasma membrane (PM). Interactions between Gag nucleocapsid (NC) and viral RNA (vRNA) are thought to drive assembly, but the exact roles of these interactions have remained poorly understood. Since previous studies have shown that Gag dimer- or trimer-forming mutants (GagZiL) lacking an NC domain can form immature capsids independent of RNA binding, it is often hypothesized that vRNA drives Gag assembly by inducing Gag to form low-ordered multimers, but is dispensable for subsequent assembly. In this study, we examined the role of vRNA in HIV-1 assembly by characterizing the distribution and mobility of Gag and Gag NC mutants at the PM using photoactivated localization microscopy (PALM) and single-particle tracking PALM (spt-PALM). We showed that both Gag and GagZiL assembly involve a similar basic assembly unit, as expected. Unexpectedly, the two proteins underwent different subsequent assembly pathways, with Gag cluster density increasing asymptotically, while GagZiL cluster density increased linearly. Additionally, the directed movement of Gag, but not GagZiL, was maintained at a constant speed, suggesting that the two proteins experience different external driving forces. Assembly was abolished when Gag was rendered monomeric by NC deletion. Collectively, these results suggest that, beyond inducing Gag to form low-ordered multimer basic assembly units, vRNA is essential in scaffolding and maintaining the stability of the subsequent assembly process. This finding should advance the current understanding of HIV-1 and, potentially, other retroviruses.}, } @article {pmid29891652, year = {2018}, author = {}, title = {Correction for Tang et al., Patterns of plant carbon, nitrogen, and phosphorus concentration in relation to productivity in China's terrestrial ecosystems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6095-E6096}, doi = {10.1073/pnas.1808126115}, pmid = {29891652}, issn = {1091-6490}, } @article {pmid29891651, year = {2018}, author = {Tigchelaar, M and Battisti, DS and Naylor, RL and Ray, DK}, title = {Future warming increases probability of globally synchronized maize production shocks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6644-6649}, pmid = {29891651}, issn = {1091-6490}, mesh = {Commerce ; Edible Grain/economics/growth & development/*supply & distribution ; *Food Supply/economics/statistics & numerical data ; Forecasting ; *Global Warming ; Hot Temperature ; Humans ; Marketing ; Plant Breeding ; Poverty ; Vulnerable Populations ; *Zea mays/growth & development ; }, abstract = {Meeting the global food demand of roughly 10 billion people by the middle of the 21st century will become increasingly challenging as the Earth's climate continues to warm. Earlier studies suggest that once the optimum growing temperature is exceeded, mean crop yields decline and the variability of yield increases even if interannual climate variability remains unchanged. Here, we use global datasets of maize production and climate variability combined with future temperature projections to quantify how yield variability will change in the world's major maize-producing and -exporting countries under 2 °C and 4 °C of global warming. We find that as the global mean temperature increases, absent changes in temperature variability or breeding gains in heat tolerance, the coefficient of variation (CV) of maize yields increases almost everywhere to values much larger than present-day values. This higher CV is due both to an increase in the SD of yields and a decrease in mean yields. For the top four maize-exporting countries, which account for 87% of global maize exports, the probability that they have simultaneous production losses greater than 10% in any given year is presently virtually zero, but it increases to 7% under 2 °C warming and 86% under 4 °C warming. Our results portend rising instability in global grain trade and international grain prices, affecting especially the ∼800 million people living in extreme poverty who are most vulnerable to food price spikes. They also underscore the urgency of investments in breeding for heat tolerance.}, } @article {pmid29891650, year = {2018}, author = {Yun, L and Chen, PJ and Kwok, KE and Angell, CS and Rundle, HD and Agrawal, AF}, title = {Competition for mates and the improvement of nonsexual fitness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6762-6767}, pmid = {29891650}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; Animal Feed ; Animals ; Cold Temperature ; *Competitive Behavior ; Drosophila melanogaster/genetics/growth & development/*physiology ; Ethanol ; Female ; Genetic Fitness ; Hot Temperature ; Inbreeding Depression ; Larva ; Male ; *Mating Preference, Animal ; Ovum ; Starch ; Zea mays ; }, abstract = {Competition for mates can be a major source of selection, not just on secondary sexual traits but across the genome. Mate competition strengthens selection on males via sexual selection, which typically favors healthy, vigorous individuals and, thus, all genetic variants that increase overall quality. However, recent studies suggest another major effect of mate competition that could influence genome-wide selection: Sexual harassment by males can drastically weaken selection on quality in females. Because of these conflicting effects, the net effect of mate competition is uncertain, although perhaps not entirely unpredictable. We propose that the environment in which mate competition occurs mediates the importance of sexual selection relative to sexual conflict and, hence, the net effect of mate competition on nonsexual fitness. To test this, we performed experimental evolution with 63 fruit fly populations adapting to novel larval conditions where each population was maintained with or without mate competition. In half the populations with mate competition, adults interacted in simple, high-density environments. In the remainder, adults interacted in more spatially complex environments in which male-induced harm is reduced. Populations evolving with mate competition in the complex environment adapted faster to novel larval environments than did populations evolving without mate competition or with mate competition in the simple environment. Moreover, mate competition in the complex environment caused a substantial reduction in inbreeding depression for egg-to-adult viability relative to the other two mating treatments. These results demonstrate that the mating environment has a substantial and predictable effect on nonsexual fitness through adaptation and purging.}, } @article {pmid29891649, year = {2018}, author = {Casalino, L and Palermo, G and Spinello, A and Rothlisberger, U and Magistrato, A}, title = {All-atom simulations disentangle the functional dynamics underlying gene maturation in the intron lariat spliceosome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6584-6589}, pmid = {29891649}, issn = {1091-6490}, mesh = {*Computer Simulation ; Introns/*genetics ; Magnesium/physiology ; *Models, Genetic ; Models, Molecular ; Molecular Dynamics Simulation ; Motion ; *Nucleic Acid Conformation ; Principal Component Analysis ; Protein Conformation ; RNA Precursors/genetics/*metabolism ; RNA Splicing/*physiology ; RNA, Fungal/genetics/metabolism ; RNA, Small Nuclear/genetics/metabolism ; Repressor Proteins/chemistry/*physiology ; Ribonucleoprotein, U5 Small Nuclear/chemistry/*physiology ; Schizosaccharomyces/genetics/metabolism ; Schizosaccharomyces pombe Proteins/chemistry/*physiology ; Spliceosomes/*physiology ; Static Electricity ; }, abstract = {The spliceosome (SPL) is a majestic macromolecular machinery composed of five small nuclear RNAs and hundreds of proteins. SPL removes noncoding introns from precursor messenger RNAs (pre-mRNAs) and ligates coding exons, giving rise to functional mRNAs. Building on the first SPL structure solved at near-atomic-level resolution, here we elucidate the functional dynamics of the intron lariat spliceosome (ILS) complex through multi-microsecond-long molecular-dynamics simulations of ∼1,000,000 atoms models. The ILS essential dynamics unveils (i) the leading role of the Spp42 protein, which heads the gene maturation by tuning the motions of distinct SPL components, and (ii) the critical participation of the Cwf19 protein in displacing the intron lariat/U2 branch helix. These findings provide unprecedented details on the SPL functional dynamics, thus contributing to move a step forward toward a thorough understanding of eukaryotic pre-mRNA splicing.}, } @article {pmid29891563, year = {2018}, author = {Zu, T and Pattamatta, A and Ranum, LPW}, title = {Repeat-Associated Non-ATG Translation in Neurological Diseases.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, doi = {10.1101/cshperspect.a033019}, pmid = {29891563}, issn = {1943-0264}, abstract = {More than 40 different neurological diseases are caused by microsatellite repeat expansions that locate within translated or untranslated gene regions, including 5' and 3' untranslated regions (UTRs), introns, and protein-coding regions. Expansion mutations are transcribed bidirectionally and have been shown to give rise to proteins, which are synthesized from three reading frames in the absence of an AUG initiation codon through a novel process called repeat-associated non-ATG (RAN) translation. RAN proteins, which were first described in spinocerebellar ataxia type 8 (SCA8) and myotonic dystrophy type 1 (DM1), have now been reported in a growing list of microsatellite expansion diseases. This article reviews what is currently known about RAN proteins in microsatellite expansion diseases and experiments that provide clues on how RAN translation is regulated.}, } @article {pmid29891561, year = {2018}, author = {Stern-Ginossar, N and Thompson, SR and Mathews, MB and Mohr, I}, title = {Translational Control in Virus-Infected Cells.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a033001}, pmid = {29891561}, issn = {1943-0264}, support = {R01 AI073898/AI/NIAID NIH HHS/United States ; R01 GM056927/GM/NIGMS NIH HHS/United States ; }, abstract = {As obligate intracellular parasites, virus reproduction requires host cell functions. Despite variations in genome size and configuration, nucleic acid composition, and their repertoire of encoded functions, all viruses remain unconditionally dependent on the protein synthesis machinery resident within their cellular hosts to translate viral messenger RNAs (mRNAs). A complex signaling network responsive to physiological stress, including infection, regulates host translation factors and ribosome availability. Furthermore, access to the translation apparatus is patrolled by powerful host immune defenses programmed to restrict viral invaders. Here, we review the tactics and mechanisms used by viruses to appropriate control over host ribosomes, subvert host defenses, and dominate the infected cell translational landscape. These not only define aspects of infection biology paramount for virus reproduction, but continue to drive fundamental discoveries into how cellular protein synthesis is controlled in health and disease.}, } @article {pmid29891000, year = {2018}, author = {Lammel, DR and Barth, G and Ovaskainen, O and Cruz, LM and Zanatta, JA and Ryo, M and de Souza, EM and Pedrosa, FO}, title = {Direct and indirect effects of a pH gradient bring insights into the mechanisms driving prokaryotic community structures.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {106}, pmid = {29891000}, issn = {2049-2618}, support = {1273253/284601/273253//Academy of Finland/International ; 223257//Norges Forskningsråd/International ; }, mesh = {Archaea/*classification/genetics ; Bacteria/*classification/genetics ; Base Sequence ; Brazil ; Ecological and Environmental Phenomena/*physiology ; Greenhouse Gases/analysis ; High-Throughput Nucleotide Sequencing ; Hydrogen-Ion Concentration ; Proton-Motive Force/*physiology ; RNA, Ribosomal, 16S/genetics ; Soil/*chemistry ; Soil Microbiology ; }, abstract = {BACKGROUND: pH is frequently reported as the main driver for prokaryotic community structure in soils. However, pH changes are also linked to "spillover effects" on other chemical parameters (e.g., availability of Al, Fe, Mn, Zn, and Cu) and plant growth, but these indirect effects on the microbial communities are rarely investigated. Usually, pH also co-varies with some confounding factors, such as land use, soil management (e.g., tillage and chemical inputs), plant cover, and/or edapho-climatic conditions. So, a more comprehensive analysis of the direct and indirect effects of pH brings a better understanding of the mechanisms driving prokaryotic (archaeal and bacterial) community structures.

RESULTS: We evaluated an agricultural soil pH gradient (from 4 to 6, the typical range for tropical farms), in a liming gradient with confounding factors minimized, investigating relationships between prokaryotic communities (16S rRNA) and physical-chemical parameters (indirect effects). Correlations, hierarchical modeling of species communities (HMSC), and random forest (RF) modeling indicated that both direct and indirect effects of the pH gradient affected the prokaryotic communities. Some OTUs were more affected by the pH changes (e.g., some Actinobacteria), while others were more affected by the indirect pH effects (e.g., some Proteobacteria). HMSC detected a phylogenetic signal related to the effects. Both HMSC and RF indicated that the main indirect effect was the pH changes on the availability of some elements (e.g., Al, Fe, and Cu), and secondarily, effects on plant growth and nutrient cycling also affected the OTUs. Additionally, we found that some of the OTUs that responded to pH also correlated with CO2, CH4, and N2O greenhouse gas fluxes.

CONCLUSIONS: Our results indicate that there are two distinct pH-related mechanisms driving prokaryotic community structures, the direct effect and "spillover effects" of pH (indirect effects). Moreover, the indirect effects are highly relevant for some OTUs and consequently for the community structure; therefore, it is a mechanism that should be further investigated in microbial ecology.}, } @article {pmid29890996, year = {2018}, author = {Ravignani, A}, title = {Correction to: Spontaneous rhythms in a harbor seal pup calls.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {376}, pmid = {29890996}, issn = {1756-0500}, abstract = {Following publication of the original article [1], the author reported an error in the first sentence of the 'Sound recordings' section. The recordings mentioned in this sentence were performed 6 days later than written. In this Correction article the original and corrected version of the sentence are presented.}, } @article {pmid29890975, year = {2018}, author = {Peixoto, FP and Braga, PHP and Mendes, P}, title = {A synthesis of ecological and evolutionary determinants of bat diversity across spatial scales.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {18}, pmid = {29890975}, issn = {1472-6785}, support = {CNPq 248975/2013-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; CNPq 150653/2015-8//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; }, abstract = {BACKGROUND: Diversity patterns result from ecological to evolutionary processes operating at different spatial and temporal scales. Species trait variation determine the spatial scales at which organisms perceive the environment. Despite this knowledge, the coupling of all these factors to understand how diversity is structured is still deficient. Here, we review the role of ecological and evolutionary processes operating across different hierarchically spatial scales to shape diversity patterns of bats-the second largest mammal order and the only mammals with real flight capability.

MAIN BODY: We observed that flight development and its provision of increased dispersal ability influenced the diversification, life history, geographic distribution, and local interspecific interactions of bats, differently across multiple spatial scales. Niche packing combined with different flight, foraging and echolocation strategies and differential use of air space allowed the coexistence among bats as well as for an increased diversity supported by the environment. Considering distinct bat species distributions across space due to their functional characteristics, we assert that understanding such characteristics in Chiroptera improves the knowledge on ecological processes at different scales. We also point two main knowledge gaps that limit progress on the knowledge on scale-dependence of ecological and evolutionary processes in bats: a geographical bias, showing that research on bats is mainly done in the New World; and the lack of studies addressing the mesoscale (i.e. landscape and metacommunity scales).

CONCLUSIONS: We propose that it is essential to couple spatial scales and different zoogeographical regions along with their functional traits, to address bat diversity patterns and understand how they are distributed across the environment. Understanding how bats perceive space is a complex task: all bats can fly, but their perception of space varies with their biological traits.}, } @article {pmid29890970, year = {2018}, author = {Fang, X and Monk, JM and Mih, N and Du, B and Sastry, AV and Kavvas, E and Seif, Y and Smarr, L and Palsson, BO}, title = {Escherichia coli B2 strains prevalent in inflammatory bowel disease patients have distinct metabolic capabilities that enable colonization of intestinal mucosa.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {66}, pmid = {29890970}, issn = {1752-0509}, support = {U01 AI124316/AI/NIAID NIH HHS/United States ; Microbial Science Initiative Graduate Research Fellowship//UC San Diego Center for Microbiome Innovation/ ; 1-U01-AI124316-01//National Institutes of Health/ ; NNF10CC1016517//Novo Nordisk/ ; }, abstract = {BACKGROUND: Escherichia coli is considered a leading bacterial trigger of inflammatory bowel disease (IBD). E. coli isolates from IBD patients primarily belong to phylogroup B2. Previous studies have focused on broad comparative genomic analysis of E. coli B2 isolates, and identified virulence factors that allow B2 strains to reside within human intestinal mucosa. Metabolic capabilities of E. coli strains have been shown to be related to their colonization site, but remain unexplored in IBD-associated strains.

RESULTS: In this study, we utilized pan-genome analysis and genome-scale models (GEMs) of metabolism to study metabolic capabilities of IBD-associated E. coli B2 strains. The study yielded three results: i) Pan-genome analysis of 110 E. coli strains (including 53 isolates from IBD studies) revealed discriminating metabolic genes between B2 strains and other strains; ii) Both comparative genomic analysis and GEMs suggested that B2 strains have an advantage in degrading and utilizing sugars derived from mucus glycan, and iii) GEMs revealed distinct metabolic features in B2 strains that potentially allow them to utilize energy more efficiently. For example, B2 strains lack the enzymes to degrade amadori products, but instead rely on neighboring bacteria to convert these substrates into a more readily usable and potentially less sought after product.

CONCLUSIONS: Taken together, these results suggest that the metabolic capabilities of B2 strains vary significantly from those of other strains, enabling B2 strains to colonize intestinal mucosa.The results from this study motivate a broad experimental assessment of the nutritional effects on E. coli B2 pathophysiology in IBD patients.}, } @article {pmid29890952, year = {2018}, author = {Winter, JM and Curry, NL and Gildea, DM and Williams, KA and Lee, M and Hu, Y and Crawford, NPS}, title = {Modifier locus mapping of a transgenic F2 mouse population identifies CCDC115 as a novel aggressive prostate cancer modifier gene in humans.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {450}, pmid = {29890952}, issn = {1471-2164}, support = {HG200366-05//Intramural Research Program National Human Genome Research Institute (US)/ ; }, mesh = {Animals ; Cell Line, Tumor ; Chromosome Mapping ; Crosses, Genetic ; Gene Expression Profiling ; Genes, Neoplasm ; Genetic Loci ; Genome-Wide Association Study ; Humans ; Male ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins/*genetics ; Polymorphism, Single Nucleotide ; Prostatic Neoplasms/*genetics/metabolism/pathology ; Quantitative Trait Loci ; RNA, Messenger/metabolism ; Sequence Analysis, RNA ; Tumor Burden ; }, abstract = {BACKGROUND: It is well known that development of prostate cancer (PC) can be attributed to somatic mutations of the genome, acquired within proto-oncogenes or tumor-suppressor genes. What is less well understood is how germline variation contributes to disease aggressiveness in PC patients. To map germline modifiers of aggressive neuroendocrine PC, we generated a genetically diverse F2 intercross population using the transgenic TRAMP mouse model and the wild-derived WSB/EiJ (WSB) strain. The relevance of germline modifiers of aggressive PC identified in these mice was extensively correlated in human PC datasets and functionally validated in cell lines.

RESULTS: Aggressive PC traits were quantified in a population of 30 week old (TRAMP x WSB) F2 mice (n = 307). Correlation of germline genotype with aggressive disease phenotype revealed seven modifier loci that were significantly associated with aggressive disease. RNA-seq were analyzed using cis-eQTL and trait correlation analyses to identify candidate genes within each of these loci. Analysis of 92 (TRAMP x WSB) F2 prostates revealed 25 candidate genes that harbored both a significant cis-eQTL and mRNA expression correlations with an aggressive PC trait. We further delineated these candidate genes based on their clinical relevance, by interrogating human PC GWAS and PC tumor gene expression datasets. We identified four genes (CCDC115, DNAJC10, RNF149, and STYXL1), which encompassed all of the following characteristics: 1) one or more germline variants associated with aggressive PC traits; 2) differential mRNA levels associated with aggressive PC traits; and 3) differential mRNA expression between normal and tumor tissue. Functional validation studies of these four genes using the human LNCaP prostate adenocarcinoma cell line revealed ectopic overexpression of CCDC115 can significantly impede cell growth in vitro and tumor growth in vivo. Furthermore, CCDC115 human prostate tumor expression was associated with better survival outcomes.

CONCLUSION: We have demonstrated how modifier locus mapping in mouse models of PC, coupled with in silico analyses of human PC datasets, can reveal novel germline modifier genes of aggressive PC. We have also characterized CCDC115 as being associated with less aggressive PC in humans, placing it as a potential prognostic marker of aggressive PC.}, } @article {pmid29890950, year = {2018}, author = {Lee, JY and Fujimoto, GM and Wilson, R and Wiley, HS and Payne, SH}, title = {Blazing Signature Filter: a library for fast pairwise similarity comparisons.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {221}, pmid = {29890950}, issn = {1471-2105}, support = {U24 CA210972/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Identifying similarities between datasets is a fundamental task in data mining and has become an integral part of modern scientific investigation. Whether the task is to identify co-expressed genes in large-scale expression surveys or to predict combinations of gene knockouts which would elicit a similar phenotype, the underlying computational task is often a multi-dimensional similarity test. As datasets continue to grow, improvements to the efficiency, sensitivity or specificity of such computation will have broad impacts as it allows scientists to more completely explore the wealth of scientific data.

RESULTS: The Blazing Signature Filter (BSF) is a highly efficient pairwise similarity algorithm which enables extensive data mining within a reasonable amount of time. The algorithm transforms datasets into binary metrics, allowing it to utilize the computationally efficient bit operators and provide a coarse measure of similarity. We demonstrate the utility of our algorithm using two common bioinformatics tasks: identifying data sets with similar gene expression profiles, and comparing annotated genomes.

CONCLUSIONS: The BSF is a highly efficient pairwise similarity algorithm that can scale to billions of comparisons without the need for specialized hardware.}, } @article {pmid29890948, year = {2018}, author = {Saad, C and Noé, L and Richard, H and Leclerc, J and Buisine, MP and Touzet, H and Figeac, M}, title = {DiNAMO: highly sensitive DNA motif discovery in high-throughput sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {223}, pmid = {29890948}, issn = {1471-2105}, abstract = {BACKGROUND: Discovering over-represented approximate motifs in DNA sequences is an essential part of bioinformatics. This topic has been studied extensively because of the increasing number of potential applications. However, it remains a difficult challenge, especially with the huge quantity of data generated by high throughput sequencing technologies. To overcome this problem, existing tools use greedy algorithms and probabilistic approaches to find motifs in reasonable time. Nevertheless these approaches lack sensitivity and have difficulties coping with rare and subtle motifs.

RESULTS: We developed DiNAMO (for DNA MOtif), a new software based on an exhaustive and efficient algorithm for IUPAC motif discovery. We evaluated DiNAMO on synthetic and real datasets with two different applications, namely ChIP-seq peaks and Systematic Sequencing Error analysis. DiNAMO proves to compare favorably with other existing methods and is robust to noise.

CONCLUSIONS: We shown that DiNAMO software can serve as a tool to search for degenerate motifs in an exact manner using IUPAC models. DiNAMO can be used in scanning mode with sliding windows or in fixed position mode, which makes it suitable for numerous potential applications.

AVAILABILITY: https://github.com/bonsai-team/DiNAMO .}, } @article {pmid29890942, year = {2018}, author = {Carruthers, M and Yurchenko, AA and Augley, JJ and Adams, CE and Herzyk, P and Elmer, KR}, title = {Correction to: De novo transcriptome assembly, annotation and comparison of four ecological and evolutionary model salmonid fish species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {448}, pmid = {29890942}, issn = {1471-2164}, abstract = {Following the publication of this article [1], the authors noticed found that they incorrectly reported the BUSCO completeness for the PhyloFish brown trout and European whitefish transcriptomes. This was due to an error in their TransDecoder pipeline and restricted to those two datasets and their interpretation. They apologise for this misreported result and thank the authors of the PhyloFish database for bringing it to their attention.}, } @article {pmid29890941, year = {2018}, author = {Furstenau, TN and Cocking, JH and Sahl, JW and Fofanov, VY}, title = {Variant site strain typer (VaST): efficient strain typing using a minimal number of variant genomic sites.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {222}, pmid = {29890941}, issn = {1471-2105}, abstract = {BACKGROUND: Targeted PCR amplicon sequencing (TAS) techniques provide a sensitive, scalable, and cost-effective way to query and identify closely related bacterial species and strains. Typically, this is accomplished by targeting housekeeping genes that provide resolution down to the family, genera, and sometimes species level. Unfortunately, this level of resolution is not sufficient in many applications where strain-level identification of bacteria is required (biodefense, forensics, clinical diagnostics, and outbreak investigations). Adding more genomic targets will increase the resolution, but the challenge is identifying the appropriate targets. VaST was developed to address this challenge by finding the minimum number of targets that, in combination, achieve maximum strain-level resolution for any strain complex. The final combination of target regions identified by the algorithm produce a unique haplotype for each strain which can be used as a fingerprint for identifying unknown samples in a TAS assay. VaST ensures that the targets have conserved primer regions so that the targets can be amplified in all of the known strains and it also favors the inclusion of targets with basal variants which makes the set more robust when identifying previously unseen strains.

RESULTS: We analyzed VaST's performance using a number of different pathogenic species that are relevant to human disease outbreaks and biodefense. The number of targets required to achieve full resolution ranged from 20 to 88% fewer sites than what would be required in the worst case and most of the resolution is achieved within the first 20 targets. We computationally and experimentally validated one of the VaST panels and found that the targets led to accurate phylogenetic placement of strains, even when the strains were not a part of the original panel design.

CONCLUSIONS: VaST is an open source software that, when provided a set of variant sites, can find the minimum number of sites that will provide maximum resolution of a strain complex, and it has many different run-time options that can accommodate a wide range of applications. VaST can be an effective tool in the design of strain identification panels that, when combined with TAS technologies, offer an efficient and inexpensive strain typing protocol.}, } @article {pmid29890940, year = {2018}, author = {Aihua, L and Shunyuan, J and Guang, Y and Ying, L and Na, G and Tong, C and Liping, K and Luqi, H}, title = {Molecular mechanism of seed dormancy release induced by fluridone compared with cod stratification in Notopterygium incisum.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {116}, pmid = {29890940}, issn = {1471-2229}, support = {81325023//National Natural Science Foundation of China/ ; ZZ2016012//China Postdoctoral Science Foundation/ ; }, mesh = {Abscisic Acid/antagonists & inhibitors ; Apiaceae/*drug effects/physiology ; Cold Temperature ; Genes, Plant/drug effects/physiology ; Germination/drug effects/physiology ; Gibberellins/metabolism ; Medicine, Chinese Traditional ; Plant Dormancy/*drug effects/physiology ; Plant Growth Regulators/antagonists & inhibitors ; Plants, Medicinal/*drug effects/physiology ; Pyridones/*pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Seeds/drug effects/physiology ; Sequence Analysis, DNA ; Transcriptome/drug effects ; }, abstract = {BACKGROUND: Notopterygium incisum is an important Chinese medicinal plant. Its mature seeds have underdeveloped embryos and are physiological dormant. We found the seeds with full developed embryos can germinate after treated by fluridone (FL), an inhibitor of abscisic acid (ABA). In order to understand the molecular mechanisms underlying seed dormancy release by FL, we compared the transcriptomic changes in dormancy release induced by two different methods, FL and cold stratification (CS) in N. incisum. We further analyzed the gene expression patterns involved in seed germination and dormancy using quantitative reverse-transcription PCR.

RESULTS: RNA-sequence analysis revealed more dramatic changes in the transcriptomes of FL than those in CS, particularly for genes involved in the biosynthesis and regulation of gibberellins (GAs) and ABA. The down-regulation of ABA biosynthesis genes and the dramatic up-regulation of NiCYP707As, an ABA catabolic gene, contributed to the reduced ABA levels in FL. The increased GA3 levels in CS-treated seeds were due to the up-regulation of NiGA3OX. Both NiABI5 (a positive ABA regulator) and NiGAI (a negative regulator of GA) were down-regulated in FL and CS. The upregulation of strigolactones (SLs; the metabolites with the same precursor as ABA) biosynthesis and regulatory genes in both FL- and CS-treated seeds indicates that SLs contribute positively to seed dormancy release in N. incisum.

CONCLUSIONS: Our results indicated that FL- and CS-seed dormancy release possibly depends on two totally different mechanisms: alleviation of the effects of ABA and potentiation of the effects of GA, respectively. However, NiABI5 and NiGAI probably function as common factors integrating the effects of ABA and GA on seed dormancy release.}, } @article {pmid29890939, year = {2018}, author = {Mokhber, M and Moradi-Shahrbabak, M and Sadeghi, M and Moradi-Shahrbabak, H and Stella, A and Nicolzzi, E and Rahmaninia, J and Williams, JL}, title = {A genome-wide scan for signatures of selection in Azeri and Khuzestani buffalo breeds.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {449}, pmid = {29890939}, issn = {1471-2164}, mesh = {Animals ; Buffaloes/*genetics ; Genome ; Genome-Wide Association Study ; Genotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; *Selection, Genetic ; }, abstract = {BACKGROUND: Identification of genomic regions that have been targets of selection may shed light on the genetic history of livestock populations and help to identify variation controlling commercially important phenotypes. The Azeri and Kuzestani buffalos are the most common indigenous Iranian breeds which have been subjected to divergent selection and are well adapted to completely different regions. Examining the genetic structure of these populations may identify genomic regions associated with adaptation to the different environments and production goals.

RESULTS: A set of 385 water buffalo samples from Azeri (N = 262) and Khuzestani (N = 123) breeds were genotyped using the Axiom® Buffalo Genotyping 90 K Array. The unbiased fixation index method (FST) was used to detect signatures of selection. In total, 13 regions with outlier FST values (0.1%) were identified. Annotation of these regions using the UMD3.1 Bos taurus Genome Assembly was performed to find putative candidate genes and QTLs within the selected regions. Putative candidate genes identified include FBXO9, NDFIP1, ACTR3, ARHGAP26, SERPINF2, BOLA-DRB3, BOLA-DQB, CLN8, and MYOM2.

CONCLUSIONS: Candidate genes identified in regions potentially under selection were associated with physiological pathways including milk production, cytoskeleton organization, growth, metabolic function, apoptosis and domestication-related changes include immune and nervous system development. The QTL identified are involved in economically important traits in buffalo related to milk composition, udder structure, somatic cell count, meat quality, and carcass and body weight.}, } @article {pmid29890223, year = {2018}, author = {Laenen, B and Patiño, J and Hagborg, A and Désamoré, A and Wang, J and Shaw, AJ and Goffinet, B and Vanderpoorten, A}, title = {Evolutionary origin of the latitudinal diversity gradient in liverworts.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {606-612}, doi = {10.1016/j.ympev.2018.06.007}, pmid = {29890223}, issn = {1095-9513}, abstract = {A latitudinal diversity gradient towards the tropics appears as one most recurrent patterns in ecology, but the mechanisms underlying this pattern remain an area of controversy. In angiosperms, the tropical conservatism hypothesis proposes that most groups originated in the tropics and are adapted to a tropical climatic regime, and that relatively few species have evolved physiological adaptations to cold, dry or unpredictable climates. This mechanism is, however, unlikely to apply across land plants, and in particular, to liverworts, a group of about 7500 species, whose ability to withstand cold much better than their tracheophyte counterparts is at odds with the tropical conservatism hypothesis. Molecular dating, diversification rate analyses and ancestral area reconstructions were employed to explore the evolutionary mechanisms that account for the latitudinal diversity gradient in liverworts. As opposed to angiosperms, tropical liverwort genera are not older than their extra-tropical counterparts (median stem age of tropical and extra-tropical liverwort genera of 24.35 ± 39.65 Ma and 39.57 ± 49.07 Ma, respectively), weakening the 'time for speciation hypothesis'. Models of ancestral area reconstructions with equal migration rates between tropical and extra-tropical regions outperformed models with asymmetrical migration rates in either direction. The symmetry and intensity of migrations between tropical and extra-tropical regions suggested by the lack of resolution in ancestral area reconstructions towards the deepest nodes are at odds with the tropical niche conservatism hypothesis. In turn, tropical genera exhibited significantly higher net diversification rates than extra-tropical ones, suggesting that the observed latitudinal diversity gradient results from either higher extinction rates in extra-tropical lineages or higher speciation rates in the tropics. We discuss a series of experiments to help deciphering the underlying evolutionary mechanisms.}, } @article {pmid29889612, year = {2019}, author = {Fennel, K and Testa, JM}, title = {Biogeochemical Controls on Coastal Hypoxia.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {105-130}, doi = {10.1146/annurev-marine-010318-095138}, pmid = {29889612}, issn = {1941-0611}, abstract = {Aquatic environments experiencing low-oxygen conditions have been described as hypoxic, suboxic, or anoxic zones; oxygen minimum zones; and, in the popular media, the misnomer "dead zones." This review aims to elucidate important aspects underlying oxygen depletion in diverse coastal systems and provides a synthesis of general relationships between hypoxia and its controlling factors. After presenting a generic overview of the first-order processes, we review system-specific characteristics for selected estuaries where adjacent human settlements contribute to high nutrient loads, river-dominated shelves that receive large inputs of fresh water and anthropogenic nutrients, and upwelling regions where a supply of nutrient-rich, low-oxygen waters generates oxygen minimum zones without direct anthropogenic influence. We propose a nondimensional number that relates the hypoxia timescale and water residence time to guide the cross-system comparison. Our analysis reveals the basic principles underlying hypoxia generation in coastal systems and provides a framework for discussing future changes.}, } @article {pmid29889611, year = {2019}, author = {Muller-Karger, FE and Astor, YM and Benitez-Nelson, CR and Buck, KN and Fanning, KA and Lorenzoni, L and Montes, E and Rueda-Roa, DT and Scranton, MI and Tappa, E and Taylor, GT and Thunell, RC and Troccoli, L and Varela, R}, title = {The Scientific Legacy of the CARIACO Ocean Time-Series Program.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {413-437}, doi = {10.1146/annurev-marine-010318-095150}, pmid = {29889611}, issn = {1941-0611}, abstract = {The CARIACO (Carbon Retention in a Colored Ocean) Ocean Time-Series Program station, located at 10.50°N, 64.66°W, observed biogeochemical and ecological processes in the Cariaco Basin of the southwestern Caribbean Sea from November 1995 to January 2017. The program completed 232 monthly core cruises, 40 sediment trap deployment cruises, and 40 microbiogeochemical process cruises. Upwelling along the southern Caribbean Sea occurs from approximately November to August. High biological productivity (320-628 g C m-2 y-1) leads to large vertical fluxes of particulate organic matter, but only approximately 9-10 g C m-2 y-1 fall to the bottom sediments (∼1-3% of primary production). A diverse community of heterotrophic and chemoautotrophic microorganisms, viruses, and protozoa thrives within the oxic-anoxic interface. A decrease in upwelling intensity from approximately 2003 to 2013 and the simultaneous overfishing of sardines in the region led to diminished phytoplankton bloom intensities, increased phytoplankton diversity, and increased zooplankton densities. The deepest waters of the Cariaco Basin exhibited long-term positive trends in temperature, salinity, hydrogen sulfide, ammonia, phosphate, methane, and silica. Earthquakes and coastal flooding also resulted in the delivery of sediment to the seafloor. The program's legacy includes climate-quality data from suboxic and anoxic habitats and lasting relationships between international researchers.}, } @article {pmid29889020, year = {2018}, author = {Bernard, K and Burdz, T and Wiebe, D and Alfa, M and Bernier, AM}, title = {Clostridium neonatale sp. nov. linked to necrotizing enterocolitis in neonates and a clarification of species assignable to the genus Clostridium (Prazmowski 1880) emend. Lawson and Rainey 2016.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2416-2423}, doi = {10.1099/ijsem.0.002827}, pmid = {29889020}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Clostridium/*classification/genetics ; DNA, Bacterial/genetics ; Enterocolitis, Necrotizing/*microbiology ; Humans ; Infant, Newborn ; Microbial Sensitivity Tests ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; }, abstract = {A description of an outbreak of necrotizing enterocolitis among neonates, linked to the putative novel species Clostridium neonatale and assignable to the genus Clostridium, was previously reported in brief but that name had never been validly published (Alfa et al. Clin Inf Dis 2002;35:S101-S105). Features of this taxon group and its phylogenetic position with respect to contemporary species in the genus Clostridium were recently reviewed and still found to be unique. Therefore, we provide here a description based on biochemical, chemotaxonomic and antimicrobial susceptibility testing (AST), matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) MS, 16S rRNA gene sequencing as well as information obtained by whole genome sequencing (WGS) for strains 99A005T and 99A006. Those two C. neonatale strains were essentially identical to each other, with genome sizes of 4 658 596-4 705 520 bp and G+C content of 28.4-28.5 mol% (WGS). AST inferred susceptibility to 14 antibiotics. MALDI-TOF spectra were unique and could potentially be used for identification. The type strain is (NML) LCDC 99A005T [=ATCC BAA-265T=CCUG 46077T=St. Boniface Hospital 30686T]. While performing this review, we found that the names of 24 validly published species assignable to the genus Clostridium had been omitted from the emended description of the genus (Lawson and Rainey Int J Syst Evol Microbiol 2016;66 :1009-1016). Those species are listed in brief here. Lastly, based on this review, we also propose that Eubacterium budayi, Eubacterium nitritogenes and Eubacterium combesii be transferred to the emended genus Clostridium, as Clostridium budayi comb. nov., Clostridium nitritogenes comb. nov. and Clostridium combesii comb. nov., respectively.}, } @article {pmid29888542, year = {2018}, author = {Kremer, LPM and Korb, J and Bornberg-Bauer, E}, title = {Reconstructed evolution of insulin receptors in insects reveals duplications in early insects and cockroaches.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {5}, pages = {305-311}, doi = {10.1002/jez.b.22809}, pmid = {29888542}, issn = {1552-5015}, abstract = {Social insects show an extreme degree of phenotypic plasticity. In highly eusocial species, this manifests in the generation of distinct castes with extreme differences in both morphology and life span. The molecular basis of these differences is highly entangled and not fully understood, but several recent studies demonstrated that insulin/insulin-like growth factor signaling (IIS) is one of the key pathways. Here, we investigate the molecular evolution of insect insulin receptors (InRs), which are membrane-bound dimers that enable IIS by relaying extracellular signals to intracellular signaling cascades. Classic models of invertebrate IIS include only one InR gene, but some recent studies on less commonly studied insects have found two InRs, which act in an antagonistic manner to facilitate polyphenism in at least one documented case. We search 22 arthropod genomes and identify several InR copies and their evolutionary origin that were lacking from previous annotations. Phylogenetic analysis shows that the two insect InR genes date back at least 400 million years to a common ancestor of winged insects. Most notably, we also identified the evolutionary origin of a third InR copy that is unique to the clade of Blattodea, just before therein the eusocial termites evolved. One of the InR paralogs consistently shows caste-biased expression in all three termites, which strongly suggests a role in caste differentiation. These results have important ramifications for past and future InR inhibition/InR knockdown experiments in insects and they provide a set of key genes regulating life span and morphology in termite castes.}, } @article {pmid29887516, year = {2018}, author = {Karfakis, N}, title = {The biopolitics of CFS/ME.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {70}, number = {}, pages = {20-28}, doi = {10.1016/j.shpsc.2018.05.009}, pmid = {29887516}, issn = {1879-2499}, mesh = {*Fatigue Syndrome, Chronic/psychology/therapy ; Humans ; *Politics ; }, abstract = {This paper argues that Chronic Fatigue Syndrome/Myalgic Encephalomyelitis (CFS/ME) constitutes a biopolitical problem, a scientific object which needs to be studied, classified and regulated. Assemblages of authorities, knowledges and techniques make CFS/ME subjects and shape their everyday conduct in an attempt to increase their supposed autonomy, wellbeing and health. CFS and CFS/ME identities are however made not only through government, scientific, and medical interventions but also by the patients themselves, a biosocial community who collaborates with scientists, educates itself about the intricacies of biomedicine, and contests psychiatric truth claims. CFS/ME is an illness trapped between medicine and psychology, an illness that is open to debate and therefore difficult to manage and standardise. The paper delineates different interventions by medicine, science, the state and the patients themselves and concludes that CFS/ME remains elusive, only partially standardised, in an on-going battle between all the different actors that want to define it for their own situated interests.}, } @article {pmid29887210, year = {2018}, author = {Irish, JD and Bailey, SE and Guatelli-Steinberg, D and Delezene, LK and Berger, LR}, title = {Ancient teeth, phenetic affinities, and African hominins: Another look at where Homo naledi fits in.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {108-123}, doi = {10.1016/j.jhevol.2018.05.007}, pmid = {29887210}, issn = {1095-8606}, abstract = {A new species of Homo, Homo naledi, was described in 2015 based on the hominin skeletal remains from the Dinaledi Chamber of the Rising Star cave system, South Africa. Subsequent craniodental comparative analyses, both phenetic and cladistic, served to support its taxonomic distinctiveness. Here we provide a new quantitative analysis, where up to 78 nonmetric crown and root traits of the permanent dentition were compared among samples of H. naledi (including remains from the recently discovered Lesedi Chamber) and eight other species from Africa: Australopithecus afarensis, Australopithecus africanus, Paranthropus boisei, Paranthropus robustus, Homo habilis, Homo erectus, Middle Pleistocene Homo sp., and Pleistocene and Holocene Homo sapiens. By using the mean measure of divergence distance statistic, phenetic affinities were calculated among samples to evaluate interspecific relatedness. The objective was to compare the results with those previously obtained, to assess further the taxonomic validity of the Rising Star hominin species. In accordance with earlier findings, H. naledi appears most similar dentally to the other African Homo samples. However, the former species is characterized by its retention and full expression of features relating to the main cusps, as well as the root numbers, with a near absence of accessory traits-including many that, based on various cladistic studies, are plesiomorphic in both extinct and extant African hominins. As such, the present findings provide additional support for the taxonomic validity of H. naledi as a distinct species of Homo.}, } @article {pmid29886504, year = {2018}, author = {Ilaslan, E and Calvel, P and Nowak, D and Szarras-Czapnik, M and Slowikowska-Hilczer, J and Spik, A and Sararols, P and Nef, S and Jaruzelska, J and Kusz-Zamelczyk, K}, title = {A Case of Two Sisters Suffering from 46,XY Gonadal Dysgenesis and Carrying a Mutation of a Novel Candidate Sex-Determining Gene STARD8 on the X Chromosome.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {4}, pages = {191-195}, doi = {10.1159/000489692}, pmid = {29886504}, issn = {1661-5433}, mesh = {Adolescent ; Base Sequence ; Chromosomes, Human, X/*genetics ; Female ; GTPase-Activating Proteins/*genetics ; Gonadal Dysgenesis, 46,XY/*genetics ; Gonads/pathology ; Humans ; Infant ; Mutation/*genetics ; Phenotype ; Sex Determination Processes/*genetics ; *Siblings ; }, abstract = {Identification of novel genes involved in sexual development is crucial for understanding disorders of sex development (DSD). Here, we propose a member of the START domain family, the X chromosome STARD8, as a DSD candidate gene. We have identified a missense mutation of this gene in 2 sisters with 46,XY gonadal dysgenesis, inherited from their heterozygous mother. Gonadal tissue of one of the sisters contained Leydig cells overloaded with cholesterol droplets, i.e., structures previously identified in 46,XY DSD patients carrying mutations in the STAR gene encoding another START domain family member, which is crucial for steroidogenesis. Based on the phenotypes of our patients, we propose a dual role of STARD8 in sexual development, namely in testes determination and testosterone synthesis. However, further studies are needed to confirm the involvement of STARD8 in sexual development.}, } @article {pmid29886258, year = {2018}, author = {Downie, HF and Standerwick, JP and Burgess, L and Natrajan, LS and Lloyd, JR}, title = {Imaging redox activity and Fe(II) at the microbe-mineral interface during Fe(III) reduction.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {582-589}, doi = {10.1016/j.resmic.2018.05.012}, pmid = {29886258}, issn = {1769-7123}, mesh = {Ferric Compounds/*metabolism ; Ferrous Compounds/*metabolism ; Geobacter/*cytology/growth & development/*metabolism ; Microscopy, Atomic Force/*methods ; Minerals/chemistry/*metabolism ; Oxidation-Reduction ; }, abstract = {Dissimilatory iron-reducing bacteria (DIRB) play an important role in controlling the redox chemistry of Fe and other transition metals and radionuclides in the environment. During bacterial iron reduction, electrons are transferred from the outer membrane to poorly soluble Fe(III) minerals, although the precise physiological mechanisms and local impact on minerals of these redox processes remain unclear. The aim of this work was to use a range of microscopic techniques to examine the local environment of Geobacter sulfurreducens grown on thin films of Fe(III)-bearing minerals, to provide insight into spatial patterns of Fe(III) reduction and electron transfer. Confocal fluorescence microscopy showed that sparse biofilms formed on the mineral coatings, while the selective Fe(II) probe RhoNox-1 revealed Fe(II) patches on the minerals sometimes co-located with cells. Atomic force microscopy highlighted thin filamentous structures extending radially from the cell surface. Further analysis using fluorescent redox dyes showed redox-active, linear nanowires that formed cell to cell connections, although they were not implicated in playing a dominant role in direct electron transfer to the Fe(III) minerals. Overall this paper provides new methods and insights on studying Fe(III) reduction and other redox transformations in situ.}, } @article {pmid29886257, year = {2018}, author = {Tkhilaishvili, T and Di Luca, M and Abbandonato, G and Maiolo, EM and Klatt, AB and Reuter, M and Möncke-Buchner, E and Trampuz, A}, title = {Real-time assessment of bacteriophage T3-derived antimicrobial activity against planktonic and biofilm-embedded Escherichia coli by isothermal microcalorimetry.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {515-521}, doi = {10.1016/j.resmic.2018.05.010}, pmid = {29886257}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteriophage T3/pathogenicity/*physiology ; Biofilms/*growth & development ; Calorimetry/methods ; Computer Systems ; Escherichia coli/*physiology/*virology ; Microbial Sensitivity Tests ; }, abstract = {Bacterial biofilms, highly resistant to the conventional antimicrobial therapy, remain an unresolved challenge pressing the medical community to investigate new and alternative strategies to fight chronic implant-associated infections. Recently, strictly lytic bacteriophages have been revalued as powerful agents to kill antibiotic-resistant bacteria even in biofilm. Here, the interaction of T3 bacteriophage and planktonic and biofilm Escherichia coli TG1, respectively, was evaluated using isothermal microcalorimetry. Microcalorimetry is a non-invasive and highly sensitive technique measuring growth-related heat production of microorganisms in real-time. Planktonic and biofilm E. coli TG1 were exposed to different titers of T3 bacteriophage, ranging from 102 to 107 PFU/ml. The incubation of T3 with E. coli TG1 showed a strong inhibition of heat production both in planktonic and biofilm already at lower bacteriophage titers (103 PFU/ml). This method could be used to screen and evaluate the antimicrobial potential of different bacteriophages, alone and in combination with antibiotics in order to improve the treatment success of biofilm-associated infections.}, } @article {pmid29886256, year = {2018}, author = {Vinner, GK and Malik, DJ}, title = {High precision microfluidic microencapsulation of bacteriophages for enteric delivery.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {522-530}, doi = {10.1016/j.resmic.2018.05.011}, pmid = {29886256}, issn = {1769-7123}, mesh = {Alginates/analysis/chemistry ; Drug Compounding/*methods ; Gastrointestinal Tract/drug effects/microbiology ; Glucuronic Acid/analysis ; Hexuronic Acids/analysis ; Humans ; Hydrogen-Ion Concentration ; Microfluidics/economics/*instrumentation/*methods ; Myoviridae/*chemistry ; Polymers/chemistry ; Polymethacrylic Acids/chemistry ; Salmonella/virology ; Salmonella Infections/therapy ; }, abstract = {A Salmonella specific bacteriophage Felix O1 (Myoviridae) was microencapsulated in a pH responsive polymer formulation. The formulation incorporated a pH responsive methacrylic acid copolymer Eudragit® S100 (10% (w/v)) with the addition of the biopolymer sodium alginate, the composition of which was varied in the range (0.5% (w/v)-2% (w/v)). The microencapsulation process employed commercially available microfluidic droplet generation devices. We have used readily available low cost microfluidic chips instead of bespoke in-house fabricated glass capillary devices which are accessible only in specialist research facilities. We show that these co-flow microfluidic devices can easily be used to prepare phage encapsulated microparticles making them suitable for use by both the phage research community and industry in order to evaluate and optimise phage compatible formulations for microencapsulation. A novelty of the work reported here is that the size of the generated monodispersed droplets could be precisely controlled in the range 50 μm-200 μm by varying the flow rates of the dispersed and continuous phases. Consequently, alginate concentration and microparticle size were shown to influence the phage release profile and the degree of acid protection afforded to phages upon exposure to simulated gastric fluid (SGF). Bigger microparticles (∼100 μm) showed better acid protection compared with smaller beads (∼50 μm) made from the same formulation. Increasing the alginate composition resulted in improved acid protection of phages for similar particle sizes. The high viscosity formulations containing higher amounts of alginate (e.g. 2% (w/v)) negatively affected ease of droplet generation in the microfluidic device thereby posing a limitation in terms of process scale-up. Felix O1 encapsulated in the formulation containing 10% (w/v) ES100 and 1% (w/v) alginate showed excellent protection upon exposure of the gelled microparticles to SGF (pH 1 for 2 h) without the use of any antacids in the encapsulation matrix. Encapsulated phages previously exposed to SGF (pH 1 for 2 h) were released at elevated pH in simulated intestinal fluid (SIF) and were shown to arrest bacterial growth in the log growth phase. We have therefore demonstrated the microencapsulation of phages using readily available microfluidic chips to produce solid dosage microcapsule forms with a rapid pH triggered release profile suitable for targeted delivery and controlled release in the gastrointestinal tract.}, } @article {pmid29886128, year = {2018}, author = {Williams, CW and Iyer, J and Liu, Y and O'Connell, KF}, title = {CDK-11-Cyclin L is required for gametogenesis and fertility in C. elegans.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {52-66}, doi = {10.1016/j.ydbio.2018.06.006}, pmid = {29886128}, issn = {1095-564X}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*embryology/genetics ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cyclin-Dependent Kinases/genetics/*metabolism ; Cyclins/genetics/*metabolism ; Female ; Fertility/physiology ; Male ; Oogenesis/*physiology ; Spermatogenesis/*physiology ; }, abstract = {CDK11, a member of the cyclin-dependent kinase family, has been implicated in a diverse array of functions including transcription, RNA processing, sister chromatid cohesion, spindle assembly, centriole duplication and apoptosis. Despite its involvement in many essential functions, little is known about the requirements for CDK11 and its partner Cyclin L in a developing multicellular organism. Here we investigate the function of CDK11 and Cyclin L during development of the nematode Caenorhabditis elegans. Worms express two CDK11 proteins encoded by distinct loci: CDK-11.1 is essential for normal male and female fertility and is broadly expressed in the nuclei of somatic and germ line cells, while CDK-11.2 is nonessential and is enriched in hermaphrodite germ line nuclei beginning in mid pachytene. Hermaphrodites lacking CDK-11.1 develop normally but possess fewer mature sperm and oocytes and do not fully activate the RAS-ERK pathway that is required for oocyte production in response to environmental cues. Most of the sperm and eggs that are produced in cdk-11.1 null animals appear to complete development normally but fail to engage in sperm-oocyte signaling suggesting that CDK-11.1 is needed at multiple points in gametogenesis. Finally, we find that CDK-11.1 and CDK-11.2 function redundantly during embryonic and postembryonic development and likely do so in association with Cyclin L. Our results thus define multiple requirements for CDK-11-Cyclin L during animal development.}, } @article {pmid29886006, year = {2018}, author = {Rose, KD and Dunn, RH and Kumar, K and Perry, JMG and Prufrock, KA and Rana, RS and Smith, T}, title = {New fossils from Tadkeshwar Mine (Gujarat, India) increase primate diversity from the early Eocene Cambay Shale.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {93-107}, doi = {10.1016/j.jhevol.2018.05.006}, pmid = {29886006}, issn = {1095-8606}, abstract = {Several new fossil specimens from the Cambay Shale Formation at Tadkeshwar Lignite Mine in Gujarat document the presence of two previously unknown early Eocene primate species from India. A new species of Asiadapis is named based on a jaw fragment preserving premolars similar in morphology to those of A. cambayensis but substantially larger. Also described is an exceptionally preserved edentulous dentary (designated cf. Asiadapis, unnamed sp. nov.) that is slightly larger and much more robust than previously known Cambay Shale primates. Its anatomy most closely resembles that of Eocene adapoids, and the dental formula is the same as in A. cambayensis. A femur and calcaneus are tentatively allocated to the same taxon. Although the dentition is unknown, exquisite preservation of the dentary of cf. Asiadapis sp. nov. enables an assessment of masticatory musculature, function, and gape adaptations, as well as comparison with an equally well-preserved dentary of the asiadapid Marcgodinotius indicus, also from Tadkeshwar. The new M. indicus specimen shows significant gape adaptations but was probably capable of only weak bite force, whereas cf. Asiadapis sp. nov. probably used relatively smaller gapes but could generate relatively greater bite forces.}, } @article {pmid29886005, year = {2018}, author = {Minwer-Barakat, R and Marigó, J and Moyà-Solà, S}, title = {The primate remains from Roc de Santa (Late Eocene, NE Spain) revisited: New taxonomic allocation.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {254-259}, doi = {10.1016/j.jhevol.2018.05.005}, pmid = {29886005}, issn = {1095-8606}, abstract = {The scarce primate remains from the late Eocene locality of Roc de Santa (Central Pyrenees, NE Spain) were first documented in 1975. This material included a mandibular fragment with P3-M2 and a maxillary fragment with P3-M3 assigned to Adapis magnus (later transferred to the genus Leptadapis), and an isolated M3 attributed to Necrolemur antiquus. However, these specimens were never described in detail. We have thoroughly studied these specimens, with the exception of the mandibular fragment, which has been lost. The maxillary fragment is much smaller than in Leptadapis magnus and shows clear morphological differences from that species; this specimen is assigned to Microchoerus hookeri. Similarly, the isolated M3 resembles that of M. hookeri in size and morphology, and can therefore be attributed to this taxon. In addition, we describe an upper incisor never reported previously, which can also be allocated to M. hookeri, representing the first description of this tooth for the species. Therefore, we conclude that the previous taxonomic determinations were mistaken and all the available primate specimens from Roc de Santa can be confidently assigned to the species M. hookeri, previously described from the same-age localities of Sossís, Spain, and Eclépens-B, Switzerland.}, } @article {pmid29885936, year = {2018}, author = {Dong, J and Kergoat, GJ and Vicente, N and Rahmadi, C and Xu, S and Robillard, T}, title = {Biogeographic patterns and diversification dynamics of the genus Cardiodactylus Saussure (Orthoptera, Grylloidea, Eneopterinae) in Southeast Asia.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {1-14}, doi = {10.1016/j.ympev.2018.06.001}, pmid = {29885936}, issn = {1095-9513}, abstract = {Southeast Asia harbors an extraordinary species richness and endemism. While only covering 4% of the Earth's landmass, this region includes four of the planet's 34 biodiversity hotspots. Its complex geological history generated a megadiverse and highly endemic biota, attracting a lot of attention, especially in the field of island biogeography. Here we used the cricket genus Cardiodactylus as a model system to study biogeographic patterns in Southeast Asia. We carried out molecular analyses to: (1) infer phylogenetic relationships based on five mitochondrial and four nuclear markers, (2) estimate divergence times and infer biogeographical ancestral areas, (3) depict colonization routes, and summarize emigration and immigration events, as well as in situ diversification, and (4) determine whether shifts in species diversification occurred during the course of Cardiodactylus evolution. Our results support the monophyly of the genus and of one of its species groups. Dating and biogeographical analyses suggest that Cardiodactylus originated in the Southwest Pacific during the Middle Eocene. Our reconstructions indicate that Southeast Asia was independently colonized twice during the Early Miocene (ca. 19-16 Million years ago), and once during the Middle Miocene (ca. 13 Million years ago), with New Guinea acting as a corridor allowing westward dispersal through four different passageways: Sulawesi, the Philippines, Java and the Lesser Sunda Islands. Sulawesi also served as a diversification hub for Cardiodactylus through a combination of high immigration and in situ diversification events, which can be accounted for by the complex geological history of the Wallacea region.}, } @article {pmid29885935, year = {2018}, author = {Rivera-Rivera, CJ and Montoya-Burgos, JI}, title = {Back to the roots: Reducing evolutionary rate heterogeneity among sequences gives support for the early morphological hypothesis of the root of Siluriformes (Teleostei: Ostariophysi).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {272-279}, doi = {10.1016/j.ympev.2018.06.004}, pmid = {29885935}, issn = {1095-9513}, abstract = {Catfishes (Teleostei: Siluriformes) are a highly diverse order within Ostariophysi that is distributed worldwide. At the base of this clade emerge three lineages with well-defined monophylies: Diplomystidae, Loricarioidei, and Siluroidei. Morphological phylogeny studies place the Diplomystidae as the earliest branching of these three lineages, but studies based on molecular phylogenetics consistently find the fast-evolving Loricarioidei instead. The high lineage evolutionary rate heterogeneity in this order and the fact that the lineage placed closest to the root in the molecular phylogenies is fast evolving, including many long branches, raises the possibility that the discrepancy between morphological and molecular phylogenies may be the result of a long branch attraction inference artifact. We test this hypothesis by using a 10-gene dataset to evaluate the arrangement of the three main siluriform lineages, and apply the LS3 and LS4 taxon sequence subsampling methods to reduce evolutionary rate heterogeneity among lineages. The initial and complete dataset supports the basal branching of Loricarioidei as in all previous molecular phylogenies, but once lineage rate heterogeneity is reduced with LS3 or LS4 through the removal of sequences disrupting homogeneity, the phylogeny shows Diplomystidae as the earliest branching group, with high supports, as proposed by morphological phylogeny. The result obtained with LS3, however, introduces the misplacement of one of the species with the highest amount of missing data, Scoloplax sp. Because the sequence sub-selection criterion of LS4 has been optimized to reduce data removal, the phylogeny resulting from the LS4-processed data is in agreement with the known intra-lineage relationships in addition to supporting the morphologically-based rooting hypothesis. Our results are the first instance in which a consensus between molecular and morphological phylogeny is reached concerning the root of this order.}, } @article {pmid29885934, year = {2018}, author = {Liang, D and Yang, X and Liu, J and Caiyin, Q and Zhao, G and Li, L and Qiao, J}, title = {Global evolution of glycosylated polyene macrolide antibiotic biosynthesis.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {239-247}, doi = {10.1016/j.ympev.2018.06.005}, pmid = {29885934}, issn = {1095-9513}, abstract = {Antibiotics are the most marvelous evolutionary products of microbes to obtain competitive advantage and maintain ecological balance. However, the origination and development of antibiotics has yet to be explicitly investigated. Due to diverse structures and similar biosynthesis, glycosylated polyene macrolides (gPEMs) were chosen to explore antibiotic evolution. A total of 130 candidate and 38 transitional gPEM clusters were collected from actinomycetes genomes, providing abundant references for phenotypic gaps in gPEM evolution. The most conserved parts of gPEM biosynthesis were found and used for phylogeny construction. On this basis, we proposed ancestral gPEM clusters at different evolutionary stages and interpreted the possible evolutionary histories in detail. The results revealed that gPEMs evolved from small rings to large rings and continuously increased structural diversity through acquiring, discarding and exchanging genes from different evolutionary origins, as well as co-evolution of functionally related proteins. The combination of horizontal gene transfers, environmental effects and host preference resulted in the diversity and worldwide distribution of gPEMs. This study is not only a useful exploration on antibiotic evolution but also an inspiration for diversity and biogeographic investigations on antibiotics in the era of Big Data.}, } @article {pmid29885933, year = {2018}, author = {Fang, L and Leliaert, F and Novis, PM and Zhang, Z and Zhu, H and Liu, G and Penny, D and Zhong, B}, title = {Improving phylogenetic inference of core Chlorophyta using chloroplast sequences with strong phylogenetic signals and heterogeneous models.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {248-255}, doi = {10.1016/j.ympev.2018.06.006}, pmid = {29885933}, issn = {1095-9513}, abstract = {Phylogenetic relationships within the green algal phylum Chlorophyta have proven difficult to resolve. The core Chlorophyta include Chlorophyceae, Ulvophyceae, Trebouxiophyceae, Pedinophyceae and Chlorodendrophyceae, but the relationships among these classes remain unresolved and the monophyly of Ulvophyceae and Trebouxiophyceae are highly controversial. We analyzed a dataset of 101 green algal species and 73 protein-coding genes sampled from complete and partial chloroplast genomes, including six newly sequenced ulvophyte genomes (Blidingia minima NIES-1837, Ulothrix zonata, Halochlorococcum sp. NIES-1838, Scotinosphaera sp. NIES-154, Caulerpa brownii and Cephaleuros sp. HZ-2017). We applied the Tree Certainty (TC) score to quantify the level of incongruence between phylogenetic trees in chloroplast genomic datasets, and show that the conflicting phylogenetic trees of core Chlorophyta stem from the most GC-heterogeneous sites. With removing the most GC-heterogeneous sites, our chloroplast phylogenomic analyses using heterogeneous models consistently support monophyly of the Chlorophyceae and of the Trebouxiophyceae, but the Ulvophyceae was resolved as polyphyletic. Our analytical framework provides an efficient approach to reconstruct the optimal phylogenetic relationships by minimizing conflicting signals.}, } @article {pmid29885781, year = {2018}, author = {Ghaly, TM and Gillings, MR}, title = {Mobile DNAs as Ecologically and Evolutionarily Independent Units of Life.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {904-912}, doi = {10.1016/j.tim.2018.05.008}, pmid = {29885781}, issn = {1878-4380}, abstract = {Mobile DNAs drive the spread of virulence and antibiotic-resistance determinants across diverse bacterial lineages. However, they have been largely overlooked as therapeutic targets, limiting our ability to prevent the spread of their clinically relevant cargo genes. Mobile DNAs adopt various behavioural, evolutionary, and ecological strategies to enhance their diversification, transmission, and replicative fitness. They can do this even at the expense of their host bacterium. Here, we explore evidence that mobile DNAs are inherently selfish, and resemble endoparasites. Viewing them as such helps us to better understand their dynamics, and ultimately, could identify ways to limit their role in the spread of resistance. Shifting our therapeutic focus towards targeting the transmission of mobile DNAs could help us to manage the resistance crisis.}, } @article {pmid29885666, year = {2018}, author = {Meng, A and Marchet, C and Corre, E and Peterlongo, P and Alberti, A and Da Silva, C and Wincker, P and Pelletier, E and Probert, I and Decelle, J and Le Crom, S and Not, F and Bittner, L}, title = {A de novo approach to disentangle partner identity and function in holobiont systems.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {105}, pmid = {29885666}, issn = {2049-2618}, support = {ANR-15-CE02-0011//Agence Nationale de la Recherche (FR)/International ; }, mesh = {Animals ; Cnidaria/*parasitology ; Computational Biology ; *Coral Reefs ; Microalgae/metabolism ; Plankton/parasitology ; Porifera/*microbiology ; Rhizaria/*parasitology ; Symbiosis/*physiology ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Study of meta-transcriptomic datasets involving non-model organisms represents bioinformatic challenges. The production of chimeric sequences and our inability to distinguish the taxonomic origins of the sequences produced are inherent and recurrent difficulties in de novo assembly analyses. As the study of holobiont meta-transcriptomes is affected by challenges invoked above, we propose an innovative bioinformatic approach to tackle such difficulties and tested it on marine models as a proof of concept.

RESULTS: We considered three holobiont models, of which two transcriptomes were previously published and a yet unpublished transcriptome, to analyze and sort their raw reads using Short Read Connector, a k-mer based similarity method. Before assembly, we thus defined four distinct categories for each holobiont meta-transcriptome: host reads, symbiont reads, shared reads, and unassigned reads. Afterwards, we observed that independent de novo assemblies for each category led to a diminution of the number of chimeras compared to classical assembly methods. Moreover, the separation of each partner's transcriptome offered the independent and comparative exploration of their functional diversity in the holobiont. Finally, our strategy allowed to propose new functional annotations for two well-studied holobionts (a Cnidaria-Dinophyta, a Porifera-Bacteria) and a first meta-transcriptome from a planktonic Radiolaria-Dinophyta system forming widespread symbiotic association for which our knowledge is considerably limited.

CONCLUSIONS: In contrast to classical assembly approaches, our bioinformatic strategy generates less de novo assembled chimera and allows biologists to study separately host and symbiont data from a holobiont mixture. The pre-assembly separation of reads using an efficient tool as Short Read Connector is an effective way to tackle meta-transcriptomic challenges and offers bright perpectives to study holobiont systems composed of either well-studied or poorly characterized symbiotic lineages and ultimately expand our knowledge about these associations.}, } @article {pmid29885665, year = {2018}, author = {Durack, J and Huang, YJ and Nariya, S and Christian, LS and Ansel, KM and Beigelman, A and Castro, M and Dyer, AM and Israel, E and Kraft, M and Martin, RJ and Mauger, DT and Rosenberg, SR and King, TS and White, SR and Denlinger, LC and Holguin, F and Lazarus, SC and Lugogo, N and Peters, SP and Smith, LJ and Wechsler, ME and Lynch, SV and Boushey, HA and , }, title = {Bacterial biogeography of adult airways in atopic asthma.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {104}, pmid = {29885665}, issn = {2049-2618}, support = {U10 HL098107/HL/NHLBI NIH HHS/United States ; P30 ES006694/ES/NIEHS NIH HHS/United States ; UM1 AI114271/AI/NIAID NIH HHS/United States ; U10 HL098103/HL/NHLBI NIH HHS/United States ; AI114271//National Institute of Allergy and Infectious Diseases/International ; U10 HL098090/HL/NHLBI NIH HHS/United States ; R01 AI129958/AI/NIAID NIH HHS/United States ; HL098107/HL/NHLBI NIH HHS/United States ; R03 HL138310/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Asthma/*microbiology/*physiopathology ; Bronchi/*microbiology ; Corynebacterium/classification/genetics/*isolation & purification ; Eosinophils/immunology ; Female ; Humans ; Inflammation/immunology/microbiology ; Male ; Microbiota/genetics ; Middle Aged ; Moraxella/classification/genetics/*isolation & purification ; Mouth Mucosa/microbiology ; Nose/microbiology ; RNA, Ribosomal, 16S/genetics ; Sputum/microbiology ; }, abstract = {BACKGROUND: Perturbations to the composition and function of bronchial bacterial communities appear to contribute to the pathophysiology of asthma. Unraveling the nature and mechanisms of these complex associations will require large longitudinal studies, for which bronchoscopy is poorly suited. Studies of samples obtained by sputum induction and nasopharyngeal brushing or lavage have also reported asthma-associated microbiota characteristics. It remains unknown, however, whether the microbiota detected in these less-invasive sample types reflect the composition of bronchial microbiota in asthma.

RESULTS: Bacterial microbiota in paired protected bronchial brushings (BB; n = 45), induced sputum (IS; n = 45), oral wash (OW; n = 45), and nasal brushings (NB; n = 27) from adults with mild atopic asthma (AA), atopy without asthma (ANA), and healthy controls (HC) were profiled using 16S rRNA gene sequencing. Though microbiota composition varied with sample type (p < 0.001), compositional similarity was greatest for BB-IS, particularly in AAs and ANAs. The abundance of genera detected in BB correlated with those detected in IS and OW (r median [IQR] 0.869 [0.748-0.942] and 0.822 [0.687-0.909] respectively), but not with those in NB (r = 0.004 [- 0.003-0.011]). The number of taxa shared between IS-BB and NB-BB was greater in AAs than in HCs (p < 0.05) and included taxa previously associated with asthma. Of the genera abundant in NB, only Moraxella correlated positively with abundance in BB; specific members of this genus were shared between the two compartments only in AAs. Relative abundance of Moraxella in NB of AAs correlated negatively with that of Corynebacterium but positively with markers of eosinophilic inflammation in the blood and BAL fluid. The genus, Corynebacterium, trended to dominate all NB samples of HCs but only half of AAs (p = 0.07), in whom abundance of this genus was negatively associated with markers of eosinophilic inflammation.

CONCLUSIONS: Induced sputum is superior to nasal brush or oral wash for assessing bronchial microbiota composition in asthmatic adults. Although compositionally similar to the bronchial microbiota, the microbiota in induced sputum are distinct, reflecting enrichment of oral bacteria. Specific bacterial genera are shared between the nasal and the bronchial mucosa which are associated with markers of systemic and bronchial inflammation.}, } @article {pmid29885287, year = {2018}, author = {Biehl, MJ and Kaylan, KB and Thompson, RJ and Gonzalez, RV and Weis, KE and Underhill, GH and Raetzman, LT}, title = {Cellular fate decisions in the developing female anteroventral periventricular nucleus are regulated by canonical Notch signaling.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {87-100}, pmid = {29885287}, issn = {1095-564X}, support = {F30 DK105760/DK/NIDDK NIH HHS/United States ; R01 DK076647/DK/NIDDK NIH HHS/United States ; T32 ES007326/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Anterior Hypothalamic Nucleus/metabolism ; Arcuate Nucleus of Hypothalamus/cytology ; Cell Differentiation/physiology ; Cell Proliferation/genetics/physiology ; Female ; Hypothalamus/metabolism ; Hypothalamus, Anterior/growth & development/*metabolism ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/*genetics/metabolism ; Kisspeptins/metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/metabolism ; Neurons/metabolism ; Receptors, Notch/genetics/*physiology ; Signal Transduction/physiology ; }, abstract = {The hypothalamic anteroventral periventricular nucleus (AVPV) is the major regulator of reproductive function within the hypothalamic-pituitary-gonadal (HPG) axis. Despite an understanding of the function of neuronal subtypes within the AVPV, little is known about the molecular mechanisms regulating their development. Previous work from our laboratory has demonstrated that Notch signaling is required in progenitor cell maintenance and formation of kisspeptin neurons of the arcuate nucleus (ARC) while simultaneously restraining POMC neuron number. Based on these findings, we hypothesized that the Notch signaling pathway may act similarly in the AVPV by promoting development of kisspeptin neurons at the expense of other neuronal subtypes. To address this hypothesis, we utilized a genetic mouse model with a conditional loss of Rbpj in Nkx2.1 expressing cells (Rbpj cKO). We noted an increase in cellular proliferation, as marked by Ki-67, in the hypothalamic ventricular zone (HVZ) in Rbpj cKO mice at E13.5. This corresponded to an increase in general neurogenesis and more TH-positive neurons. Additionally, an increase in OLIG2-positive early oligodendrocytic precursor cells was observed at postnatal day 0 in Rbpj cKO mice. By 5 weeks of age in Rbpj cKO mice, TH-positive cells were readily detected in the AVPV but few kisspeptin neurons were present. To elucidate the direct effects of Notch signaling on neuron and glia differentiation, an in vitro primary hypothalamic neurosphere assay was employed. We demonstrated that treatment with the chemical Notch inhibitor DAPT increased mKi67 and Olig2 mRNA expression while decreasing astroglial Gfap expression, suggesting Notch signaling regulates both proliferation and early glial fate decisions. A modest increase in expression of TH in both the cell soma and neurite extensions was observed after extended culture, suggesting that inhibition of Notch signaling alone is enough to bias progenitors towards a dopaminergic fate. Together, these data suggest that Notch signaling restricts early cellular proliferation and differentiation of neurons and oligodendrocytes both in vivo and in vitro and acts as a fate selector of kisspeptin neurons.}, } @article {pmid29885286, year = {2018}, author = {Bush, JO and Andersson, ER}, title = {Editorial: Signaling pathways instruct the blueprint of life.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.06.002}, pmid = {29885286}, issn = {1095-564X}, } @article {pmid29884883, year = {2018}, author = {Reeves, MB}, title = {Author Correction: Viral programming of progenitor cell commitment.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {845}, doi = {10.1038/s41564-018-0183-x}, pmid = {29884883}, issn = {2058-5276}, abstract = {In the version of this News & Views originally published, ref. 6 was incorrectly cited instead of ref. 5 at the end of the sentence shown below. This has now been corrected."Indeed, a proof of concept study has shown that latently expressed US28 can be targeted using an immunotoxin-based approach to eliminate infected cells in vitro5."}, } @article {pmid29884879, year = {2018}, author = {Koch, L}, title = {Chromosome interaction hubs around nuclear bodies.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {470-471}, doi = {10.1038/s41576-018-0026-x}, pmid = {29884879}, issn = {1471-0064}, } @article {pmid29884650, year = {2018}, author = {Krishnan, GP and González, OC and Bazhenov, M}, title = {Origin of slow spontaneous resting-state neuronal fluctuations in brain networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6858-6863}, pmid = {29884650}, issn = {1091-6490}, mesh = {Brain/*physiology ; *Computer Simulation ; Humans ; *Models, Neurological ; Nerve Net/*physiology ; Sodium-Potassium-Exchanging ATPase/metabolism ; Symporters/metabolism ; Synaptic Transmission/*physiology ; alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic Acid/metabolism ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {Resting- or baseline-state low-frequency (0.01-0.2 Hz) brain activity is observed in fMRI, EEG, and local field potential recordings. These fluctuations were found to be correlated across brain regions and are thought to reflect neuronal activity fluctuations between functionally connected areas of the brain. However, the origin of these infra-slow resting-state fluctuations remains unknown. Here, using a detailed computational model of the brain network, we show that spontaneous infra-slow (<0.05 Hz) activity could originate due to the ion concentration dynamics. The computational model implemented dynamics for intra- and extracellular K+ and Na+ and intracellular Cl- ions, Na+/K+ exchange pump, and KCC2 cotransporter. In the network model simulating resting awake-like brain state, we observed infra-slow fluctuations in the extracellular K+ concentration, Na+/K+ pump activation, firing rate of neurons, and local field potentials. Holding K+ concentration constant prevented generation of the infra-slow fluctuations. The amplitude and peak frequency of this activity were modulated by the Na+/K+ pump, AMPA/GABA synaptic currents, and glial properties. Further, in a large-scale network with long-range connections based on CoCoMac connectivity data, the infra-slow fluctuations became synchronized among remote clusters similar to the resting-state activity observed in vivo. Overall, our study proposes that ion concentration dynamics mediated by neuronal and glial activity may contribute to the generation of very slow spontaneous fluctuations of brain activity that are reported as the resting-state fluctuations in fMRI and EEG recordings.}, } @article {pmid29884440, year = {2018}, author = {Galli, LM and Santana, F and Apollon, C and Szabo, LA and Ngo, K and Burrus, LW}, title = {Corrigendum to "Direct visualization of the Wntless-induced redistribution of WNT1 in developing chick embryos" [Dev. Biol. 2018 15 439(2) 53-64].}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {205}, doi = {10.1016/j.ydbio.2018.05.025}, pmid = {29884440}, issn = {1095-564X}, } @article {pmid29884244, year = {2018}, author = {Liu, X and Li, M and Castelle, CJ and Probst, AJ and Zhou, Z and Pan, J and Liu, Y and Banfield, JF and Gu, JD}, title = {Insights into the ecology, evolution, and metabolism of the widespread Woesearchaeotal lineages.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {102}, pmid = {29884244}, issn = {2049-2618}, support = {41506163//National Natural Science Foundation of China/International ; 31622002//National Natural Science Foundation of China/International ; 3160010182//National Natural Science Foundation of China/International ; }, mesh = {Archaea/*classification/genetics/*metabolism ; Ecosystem ; *Evolution, Molecular ; Genome, Archaeal/genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: As a recently discovered member of the DPANN superphylum, Woesearchaeota account for a wide diversity of 16S rRNA gene sequences, but their ecology, evolution, and metabolism remain largely unknown.

RESULTS: Here, we assembled 133 global clone libraries/studies and 19 publicly available genomes to profile these patterns for Woesearchaeota. Phylogenetic analysis shows a high diversity with 26 proposed subgroups for this recently discovered archaeal phylum, which are widely distributed in different biotopes but primarily in inland anoxic environments. Ecological patterns analysis and ancestor state reconstruction for specific subgroups reveal that oxic status of the environments is the key factor driving the distribution and evolutionary diversity of Woesearchaeota. A selective distribution to different biotopes and an adaptive colonization from anoxic to oxic environments can be proposed and supported by evidence of the presence of ferredoxin-dependent pathways in the genomes only from anoxic biotopes but not from oxic biotopes. Metabolic reconstructions support an anaerobic heterotrophic lifestyle with conspicuous metabolic deficiencies, suggesting the requirement for metabolic complementarity with other microbes. Both lineage abundance distribution and co-occurrence network analyses across diverse biotopes confirmed metabolic complementation and revealed a potential syntrophic relationship between Woesearchaeota and methanogens, which is supported by metabolic modeling. If correct, Woesearchaeota may impact methanogenesis in inland ecosystems.

CONCLUSIONS: The findings provide an ecological and evolutionary framework for Woesearchaeota at a global scale and indicate their potential ecological roles, especially in methanogenesis.}, } @article {pmid29884242, year = {2018}, author = {Grove, BE and Schougaard, LM and Hjollund, NH and Ivarsen, P}, title = {Self-rated health, quality of life and appetite as predictors of initiation of dialysis and mortality in patients with chronic kidney disease stages 4-5: a prospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {371}, pmid = {29884242}, issn = {1756-0500}, mesh = {Aged ; *Appetite ; Endpoint Determination ; Female ; Follow-Up Studies ; *Health Status ; Humans ; Kidney Function Tests ; Kidney Transplantation ; Male ; Patient Reported Outcome Measures ; Prospective Studies ; *Quality of Life ; Renal Dialysis/*mortality ; Renal Insufficiency, Chronic/*mortality/physiopathology ; *Self Report ; }, abstract = {OBJECTIVE: Patient-reported health status, including symptom burden, functional status and quality of life, are important measures of health in patients with chronic kidney disease. We aimed to investigate patient-reported outcomes (PRO) on self-rated health, appetite, quality of life and their associations with clinical outcomes. We conducted a prospective observational cohort study. Data was collected at baseline using a PRO questionnaire. The primary outcomes were initiation of dialysis, transplantation and mortality. Kaplan-Meier curves and multivariable Cox proportional hazards regression analyses were used.

RESULTS: A total of 126 patients with chronic kidney disease with an eGFR of ≤ 25 mL/min/1.73 m2 were followed for a median of 321 (range 10-523) days. Poor appetite was associated with mortality (hazard ratio 20.9, 95% CI 3.7-129.8). Initiation of dialysis was associated with low self-rated health (hazard ratio 5.2, 95% CI 1.2-24.0). Mean decline in estimated glomerular filtration rate was - 0.9 mL/min/1.73 m2 (95% CI - 1.6 to - 0.2). Decline in self-rated health (p = 0.001) and appetite (p = 0.002) were correlated with reduction in renal function.}, } @article {pmid29884241, year = {2018}, author = {Atif, M and Anwar, Z and Fatima, RK and Malik, I and Asghar, S and Scahill, S}, title = {Analysis of tuberculosis treatment outcomes among pulmonary tuberculosis patients in Bahawalpur, Pakistan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {370}, pmid = {29884241}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Demography ; Female ; Humans ; Infant ; Infant, Newborn ; Logistic Models ; Male ; Middle Aged ; Pakistan/epidemiology ; Treatment Outcome ; Tuberculosis, Pulmonary/*drug therapy/*epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Monitoring tuberculosis treatment outcomes and understanding the reasons for unsuccessful treatment are important indicators for evaluating the performance of the national tuberculosis control program. The aim of this study was to evaluate the treatment outcomes among pulmonary TB (PTB) patients and identify the predictors of unsuccessful treatment outcome.

RESULTS: Treatment success rate of 67.8% among new and retreatment PTB patients and 69% in new smear positive PTB patients was observed. Close to 21% (20.9%) and 15.7% PTB and new smear positive PTB patients had loss to follow-up during treatment. Overall, older patients (AOR 1.02; 95% CI 1.01-1.0), smokers (AOR 1.65; 95% CI 1.02-2.67) and retreatment cases of TB (AOR 2.34; 95% CI 1.43-3.84) were at greater risk of having unsuccessful treatment outcomes. Moreover, sputum positivity at 2 months (AOR 13.78; 95% CI 5.09-37.26) was a significant predictor of poor treatment outcomes in new smear positive PTB patients. The treatment success rate among PTB patients was lower than the recommended 85% success rate. TB patients at higher risk of unsuccessful treatment outcomes should be provided with enhanced supervision and treatment monitoring to improve the success rate of TB management in Pakistan.}, } @article {pmid29884239, year = {2018}, author = {Morgan, MJ and Frazho, JK}, title = {Comparison of TPLO tibial tuberosity fractures with and without an in situ rotational pin.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {368}, pmid = {29884239}, issn = {1756-0500}, mesh = {Animals ; *Bone Nails ; Dogs ; Female ; Logistic Models ; Male ; Multivariate Analysis ; Osteotomy/*adverse effects ; *Rotation ; Tibia/diagnostic imaging/*surgery ; Tibial Fractures/diagnostic imaging/*etiology ; }, abstract = {OBJECTIVE: Cranial cruciate ligament (CCL) rupture is a common cause of pelvic limb lameness in dogs. The tibial plateau leveling osteotomy (TPLO) is a well-described surgical procedure that treats CCL ruptures. The objective of this study was to compare the risk of tibial tuberosity fractures from TPLO procedures using a TPLO reduction pin in situ versus patients with a TPLO reduction pin removed at the time of surgery. Our hypothesis is that patients with a TPLO reduction pin left in situ will have a decreased incidence of tibial tuberosity fractures.

RESULTS: A total of 400 dogs that fitted the criteria of 200 consecutive TPLO surgeries performed with each group were included in the study. The Student's t-test revealed a statistically significant difference in fractures observed in group 1 (in situ pin) and group 2 (no pin). In univariate logistic regression analysis, only the covariate for the presence of the reduction pin was associated with a statistically significant reduction in the likelihood of tibial tuberosity fracture. In the multivariate model, the presence of the reduction pin was associated with an approximate 92% reduction in the likelihood of tibial tuberosity fracture.}, } @article {pmid29884232, year = {2018}, author = {Zhang, XY and Sukhchuluun, G and Bo, TB and Chi, QS and Yang, JJ and Chen, B and Zhang, L and Wang, DH}, title = {Huddling remodels gut microbiota to reduce energy requirements in a small mammal species during cold exposure.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {103}, pmid = {29884232}, issn = {2049-2618}, mesh = {Adaptation, Physiological/*physiology ; Animals ; Arvicolinae/*microbiology/*physiology ; Basal Metabolism/physiology ; Behavior, Animal/physiology ; Body Temperature/physiology ; Cecum/*microbiology ; *Cold Temperature ; Fatty Acids, Volatile/blood ; Female ; Gastrointestinal Microbiome/*physiology ; Thermogenesis/*physiology ; }, abstract = {BACKGROUND: Huddling is highly evolved as a cooperative behavioral strategy for social mammals to maximize their fitness in harsh environments. Huddling behavior can change psychological and physiological responses. The coevolution of mammals with their microbial communities confers fitness benefits to both partners. The gut microbiome is a key regulator of host immune and metabolic functions. We hypothesized that huddling behavior altered energetics and thermoregulation by shaping caecal microbiota in small herbivores. Brandt's voles (Lasiopodomys brandtii) were maintained in a group (huddling) or as individuals (separated) and were exposed to warm (23 ± 1 °C) and cold (4 ± 1 °C) air temperatures (Ta).

RESULTS: Voles exposed to cold Ta had higher energy intake, resting metabolic rate (RMR) and nonshivering thermogenesis (NST) than voles exposed to warm Ta. Huddling voles had lower RMR and NST than separated voles in cold. In addition, huddling voles had a higher surface body temperature (Tsurface), but lower core body temperature (Tcore) than separated voles, suggesting a lower set-point of Tcore in huddling voles. Both cold and huddling induced a marked variation in caecal bacterial composition, which was associated with the lower Tcore. Huddling voles had a higher α and β-diversity, abundance of Lachnospiraceae and Veillonellaceae, but lower abundance of Cyanobacteria, Tenericutes, TM7, Comamonadaceae, and Sinobacteraceae than separated voles. Huddling or cold resulted in higher concentrations of short-chain fatty acids (SCFAs), particularly acetic acid and butyric acid when compared to their counterparts. Transplantation of caecal microbiota from cold-separated voles but not from cold-huddling voles induced significant increases in energy intake and RMR compared to that from warm-separated voles.

CONCLUSIONS: These findings demonstrate that the remodeling of gut microbiota, which is associated with a reduction in host Tcore, mediates cold- and huddling-induced energy intake and thermoregulation and therefore orchestrates host metabolic and thermal homeostasis. It highlights the coevolutionary mechanism of host huddling and gut microbiota in thermoregulation and energy saving for winter survival in endotherms.}, } @article {pmid29884230, year = {2018}, author = {Gerensea, H and Teklay, H}, title = {Trend of hypertension morbidity and mortality in Tigray Region from 2011 to 2015, Tigray, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {375}, pmid = {29884230}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Demography ; Ethiopia/epidemiology ; Female ; Humans ; Hypertension/*mortality ; Male ; Middle Aged ; Morbidity ; }, abstract = {OBJECTIVE: Hypertension in developing countries were not considered as a major concern. This lack of concern can be explained by the health policy and research of the past years, which had its main focus on infectious diseases but this study focuses on 4 years trend of hypertension mortality and morbidity. A facility based retrospective health management information system record assessment was carried out.

RESULT: Of the total 66,099 cases registered in the Health Management Information system book, 27,601 were males and 38,498 females. Considering the variation in each year, the overall trend of hypertension mortality has decreased from 32 in 2011/12 to 25 in 2014/15. The number of patients died in 2011 was 1.6 times higher than those who died in 2012. The rate admission of in inpatient and outpatient department visit is increasing from 9257 to 23,633 and 9799 to 24,425 respectively with in 4 years. Though there is variation among reports regarding the rate of morbidity and mortality, Tigray region has been improving its health care for hypertensive patients, which results in a decreasing mortality rate while the morbidity is still alarming.}, } @article {pmid29884229, year = {2018}, author = {Nedi, T and White, PJ and Coupar, IM and Irving, HR}, title = {Effect of the 5-HT4 receptor agonist tegaserod on the expression of GRK2 and GRK6 in the rat gastrointestinal tract.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {362}, pmid = {29884229}, issn = {1756-0500}, mesh = {Animals ; G-Protein-Coupled Receptor Kinase 2/*metabolism ; G-Protein-Coupled Receptor Kinases/*metabolism ; Gastrointestinal Tract/drug effects/*metabolism ; Indoles/*pharmacology ; Male ; Rats, Sprague-Dawley ; Receptors, Serotonin, 5-HT4/*metabolism ; Serotonin 5-HT4 Receptor Agonists/*pharmacology ; Time Factors ; }, abstract = {OBJECTIVE: Tegaserod is a 5-hydroxytryptamine type 4 (5-HT4) receptor agonist, formerly used in treating constipation predominant irritable bowel syndrome, which desensitizes 5-HT4 receptors in rat oesophagus and colon in vitro. Desensitization of 5-HT4 receptors is regulated by G-protein coupled receptor kinases. This study was designed to assess the effect of 5-HT4 receptor activation on the expression of GRK2 and GRK6 in the rat oesophagus and distal colon by acute administration of tegaserod.

RESULTS: Rats were treated with a single dose of tegaserod (5 mg/kg) and tissue samples of the oesophagus and distal colon were prepared and level of GRK2 and GRK6 protein expression was determined using western blotting. The immunodensity of GRK2 and GRK6 was normalized against the loading control β-actin and compared with control animals. Acute administration of tegaserod for 1, 2, 3, 4, 6, and 8 h did not change significantly the immunodensity of GRK2 or GRK6 in the oesophagus or GRK2 in the distal colon when compared with control animals. This may indicate that the basal level of GRK2 and GRK6 expression is sufficient to regulate the desensitization of 5-HT4 receptors in acute drug treatment.}, } @article {pmid29884226, year = {2018}, author = {Shima, H and Miya, K and Okada, K and Minakuchi, J and Kawashima, S}, title = {Sucroferric oxyhydroxide decreases serum phosphorus level and fibroblast growth factor 23 and improves renal anemia in hemodialysis patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {363}, pmid = {29884226}, issn = {1756-0500}, mesh = {Aged ; Anemia/*drug therapy/*etiology ; Demography ; Drug Combinations ; Female ; Ferric Compounds/pharmacology/*therapeutic use ; Fibroblast Growth Factors/*blood ; Humans ; Male ; Phosphates/*blood ; Renal Dialysis/*adverse effects ; Sucrose/pharmacology/*therapeutic use ; Treatment Outcome ; }, abstract = {OBJECTIVE: Sucroferric oxyhydroxide, a novel iron-based phosphate-binder, has been shown to have beneficial effects in lowering serum phosphorus levels and improving renal anemia in clinical studies. Although an effect of this agent on fibroblast growth factor 23 (FGF23) has been reported in an animal study, there is little clinical data supporting this finding. This study aimed to evaluate the effect on chronic kidney disease-mineral and bone disorder, FGF23, renal anemia, iron-related parameters, adverse events of sucroferric oxyhydroxide in hemodialysis patients.

RESULTS: Hemodialysis patients, receiving existing hyperphosphatemia drugs with insufficient benefit, were administered sucroferric oxyhydroxide with/without calcium carbonate for 16 weeks. Serum phosphorus level declined rapidly in Week 8 (p < 0.0001) and this decrease persisted until Week 16 (p < 0.0001). FGF23 decreased (p = 0.0412, Week 16), and hemoglobin increased (p < 0.0001, Week 16). Cumulative dose of erythropoiesis-stimulating agents (p = 0.0122, Week 16), and intravenous iron (p = 0.0233, Week 12) decreased. All adverse reactions were mild, and diarrhea was the most frequently observed adverse reaction (16.7%). Therefore, hyperphosphatemia treatment with sucroferric oxyhydroxide may safely improve serum phosphorus level, renal anemia, FGF23, and other factors that affect the prognosis of hemodialysis patients.}, } @article {pmid29884222, year = {2018}, author = {Hayashi, H and Abe, M and Matsuoka, B}, title = {Handgrip exercise by the non-affected hand increases venous return in the contralateral axillary vein in patients with stroke: a pilot study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {374}, pmid = {29884222}, issn = {1756-0500}, support = {JP 16K21468//Japan Society for the Promotion of Science/ ; }, mesh = {Adult ; Aged ; Axillary Vein/*physiopathology ; Exercise/*physiology ; Hand/*physiopathology ; Hand Strength/*physiology ; Hemodynamics ; Humans ; Male ; Middle Aged ; Pilot Projects ; Resistance Training ; Stroke/*physiopathology ; }, abstract = {OBJECTIVE: Treatment of hand edema is important for maintaining upper limb function in patients with stroke, although the effects of many such treatments have been limited. This study aimed to examine, using ultrasound, the effect of handgrip exercise by the non-affected hand of stroke patients on venous return in the affected upper limb.

RESULTS: Seven men participated, within 6 months of a unilateral first-ever stroke. With the patient supine, examinations were performed on the axillary vein of the affected side. The diameter and flow velocity of the axillary vein on the affected side were measured during two regimens: at rest or during rhythmic resistance exercise (30% of maximum grip strength for 20 s) performed by the non-affected hand. The venous flow volume in the axillary vein was then calculated using the data obtained. During resistance exercise by the non-affected hand, there were significant increases in both venous flow velocity (p = 0.01, d = - 0.80) and volume (p = 0.01, d = - 0.74) on the affected side, compared with baseline. The present preliminary study found that rhythmic resistance exercise with the non-affected hand increased venous flow velocity and volume in the affected upper limb of patients with stroke.}, } @article {pmid29884220, year = {2018}, author = {Hashmi, AA and Naz, S and Hashmi, SK and Hussain, ZF and Irfan, M and Bakar, SMA and Faridi, N and Khan, A and Edhi, MM}, title = {Cytokeratin 5/6 and cytokeratin 8/18 expression in triple negative breast cancers: clinicopathologic significance in South-Asian population.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {372}, pmid = {29884220}, issn = {1756-0500}, mesh = {Adult ; Asia ; Female ; Humans ; Keratins/*metabolism ; Middle Aged ; Triple Negative Breast Neoplasms/*metabolism/*pathology ; }, abstract = {OBJECTIVE: Cytokeratin 5/6 and Cytokeratin 8/18 are basal and luminal markers of breast cancer and they have pathological and prognostic significance in breast cancer. We performed Cytokeratin 5/6 and CK8/18 immunohistochemistry on 150 cases of triple negative breast cancers and association with various clinicopathological features was evaluated.

RESULTS: Positive CK5/6 expression was noted in 8% (12 cases) of TNBC while 2.4% (4 cases) showed focal positive (< 10%) and 89.3% (134) were negative with CK5/6. Complete loss of CK8/18 expression was seen in 4.7% (7 cases) while 32.7% (49 cases) revealed focal loss of CK8/18 and 62.7% (94 cases) showed intact normal expression of CK8/18. No significant association of CK5/6 and CK8/18 with various clinicopathological parameters was observed. We found a low expression of basal cytokeratin (CK5/6) in TNBC our studied population, while loss/altered expression of CK8/18 in approximately 38% of TNBC. Although no prognostic relevance of these finding was noted in our study, however these findings are different from those reported in literature in other parts of the world. Therefore we suggest a more through immunohistochemical and genomic profiling of TNBC in our population for better understanding of this disease in this part of the world.}, } @article {pmid29884219, year = {2018}, author = {Alaoui, N and El Alaoui, MA and Touil, N and El Annaz, H and Melloul, M and Tagajdid, R and Hjira, N and Boui, M and El Fahime, EM and Mrani, S}, title = {Prevalence of resistance to integrase strand-transfer inhibitors (INSTIs) among untreated HIV-1 infected patients in Morocco.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {369}, pmid = {29884219}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Amino Acid Sequence ; Child ; Demography ; *Drug Resistance, Viral ; Female ; HIV Infections/*drug therapy/*epidemiology ; HIV Integrase Inhibitors/*therapeutic use ; HIV-1/*physiology ; Humans ; Integrases/chemistry/genetics ; Likelihood Functions ; Male ; Morocco/epidemiology ; Phylogeny ; Prevalence ; Young Adult ; }, abstract = {OBJECTIVE: The integrase strand-transfer inhibitors (INSTIs) are an important class in the arsenal of antiretroviral drugs designed to block the integration of HIV-1 cDNA into the host DNA through the inhibition of DNA strand transfer. In this study for the first time in Morocco, the complete HIV-1 integrase gene was analysed from newly diagnosed patients to evaluate the prevalence of natural polymorphisms and INSTIs resistance-associated mutations in the integrase gene.

RESULTS: The 864pb IN coding region was successfully sequenced from plasma sample for 77 among 80 antiretroviral naïve patients. The sequences were interpreted for drug resistance according to the Stanford algorithm. Sixty samples were HIV-1 subtype B (78%), fourteen CRF02_AG (18%), two subtype C and one subtype A. Overall 81 of 288 (28%) amino acid IN positions presented at least one polymorphism each. We found 18 (36.73%), 42 (25.76%) and 21 (27.27%) of polymorphic residues assigned to the N-Terminal Domain, Catalytic Core Domaine and the C-Terminal Domain positions respectively. Primary INSTIs resistance mutation were absent, however secondary mutations L74IM, T97A were detected in four samples (5.2%). These results demonstrate that untreated HIV-1 infected Moroccans will be susceptible to INSTIs.}, } @article {pmid29884218, year = {2018}, author = {Hesse, M and Weber, R and Glünder, G}, title = {Antibody titers in turkeys increase after multiple booster vaccinations with an attenuated Salmonella live vaccine.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {367}, pmid = {29884218}, issn = {1756-0500}, mesh = {Animals ; Antibodies, Bacterial/blood/*immunology ; Cecum/microbiology ; Cloaca/microbiology ; *Immunization, Secondary ; Liver/microbiology ; Salmonella Infections/blood/immunology/microbiology ; Salmonella Vaccines/*immunology ; Spleen/microbiology ; Turkeys/*immunology/*microbiology ; *Vaccination ; Vaccines, Attenuated/*immunology ; }, abstract = {OBJECTIVE: Human Salmonellosis is one of the most frequently reported foodborne zoonoses in the European Union. The most common source of human infections is the consumption of poultry products. Besides management and hygiene practices vaccination of poultry livestock is seen as one way to reduce Salmonella infections in humans. Turkey flocks in Europe are frequently infected with Salmonella and until recently there was no live vaccine for turkeys available. The aim of the present study was to examine the development of humoral antibodies after repeated vaccination with a bivalent live Salmonella vaccine containing attenuated Salmonella Typhimurium and Salmonella Enteritidis strains. Furthermore the colonization of the caecum with the vaccine strains and their spread to liver and spleen as well as the course of their fecal excretion was observed.

RESULTS: Antibody production was hardly detectable after the first vaccination but increased after booster vaccinations. Both the Salmonella Enteritidis and the Salmonella Typhimurium vaccine strain were reisolated from caecum contents and organ samples. After booster vaccinations the re-isolation rates were reduced. The shedding of the vaccine strains was most pronounced after the first vaccination.}, } @article {pmid29884216, year = {2018}, author = {Omar, SM and Musa, IR and Osman, OE and Adam, I}, title = {Assessment of glycemic control in type 2 diabetes in the Eastern Sudan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {373}, pmid = {29884216}, issn = {1756-0500}, mesh = {Diabetes Mellitus, Type 2/*complications ; Female ; Humans ; Hyperglycemia/*complications ; Male ; Middle Aged ; Regression Analysis ; Sudan ; }, abstract = {OBJECTIVES: A cross-sectional study was conducted in Gadarif, eastern Sudan to assess glycaemic control among adult patients with type 2 diabetes in eastern Sudan. Poor glycaemic control was defined as HbA1c level of ≥ 7.0%. Questionnaire was used to gathered sociodemographic and clinical characteristics.

RESULTS: A total of 339 patients (69.9% were women) were enrolled in the study. The mean age of the participants was 54.8 (12.8) years. Approximately more than two-thirds (n = 243, 71.7%) of the participants were using oral glucose control agents. A round one-fifth (22.1%) of the participants were using insulin and only 6.2% of them were using both insulin and oral glucose control agents. The rate of poor glycemic control was 71.9%. In logistic regression analyses, duration of diabetes, medications used, and the triglycerides were not associated with poor glycemic control. However, being unmarried (OR = 3.64, 95% CI 1.21-10.90), adding sugar to the drinks (OR = 1.84, 95% CI 1.11-3.05, P = 0.017) and high cholesterol level (OR = 1.01, 95% CI 1.01-1.02.) were associated with poor glycemic control. In summary the rate of uncontrolled type 2 diabetes mellitus was considerably high especially among being unmarried patients and patients who were adding sugar to the drinks.}, } @article {pmid29884214, year = {2018}, author = {Scherer, U and Tiedemann, R and Schlupp, I}, title = {Male size, not female preferences influence female reproductive success in a poeciliid fish (Poecilia latipinna): a combined behavioural/genetic approach.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {364}, pmid = {29884214}, issn = {1756-0500}, mesh = {Animals ; *Behavior, Animal ; *Body Size ; Female ; Male ; Poecilia/*anatomy & histology/*genetics ; Reproduction/*physiology ; *Sex Characteristics ; Sexual Behavior, Animal/*physiology ; }, abstract = {OBJECTIVE: We investigated the potential role of indirect benefits for female mate preferences in a highly promiscuous species of live-bearing fishes, the sailfin molly Poecilia latipinna using an integrative approach that combines methods from animal behavior, life-history evolution, and genetics. Males of this species solely contribute sperm for reproduction, and consequently females do not receive any direct benefits. Despite this, females typically show clear mate preferences. It has been suggested that females can increase their reproductive success through indirect benefits from choosing males of higher quality.

RESULTS: Although preferences for large body size have been recorded as an honest signal for genetic quality, this particular study resulted in female preference being unaffected by male body size. Nonetheless, larger males did sire more offspring, but with no effect on offspring quality. This study presents a methodical innovation by combining preference testing with life history measurements-such as the determination of the dry weight of fish embryos-and paternity analyses on single fish embryos.}, } @article {pmid29884212, year = {2018}, author = {Vibholm, HA and Pedersen, J and Faltinsen, E and Marcussen, MH and Gluud, C and Storebø, OJ}, title = {Training, executive, attention and motor skills (TEAMS) training versus standard treatment for preschool children with attention deficit hyperactivity disorder: a randomised clinical trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {366}, pmid = {29884212}, issn = {1756-0500}, mesh = {Attention/*physiology ; Attention Deficit Disorder with Hyperactivity/*physiopathology ; Child, Preschool ; Executive Function/*physiology ; Female ; Humans ; Linear Models ; Male ; Motor Skills/*physiology ; }, abstract = {OBJECTIVE: This study compared the effectiveness of manualised training, executive, attention, and motor skills (TEAMS) training versus standard treatment in preschool children with attention deficit hyperactivity disorder (ADHD). We conducted a randomised parallel group, single-blinded, superiority trial. The primary outcome was ADHD symptoms and the secondary outcome was functionality. Parents and primary school teachers assessed outcomes at pretreatment, posttreatment, and at one, three, and 6 months follow-up.

RESULTS: In total, 67 children (aged 3-6 years) were randomised. In the TEAMS group, 32 out of 33 (97%) participants completed the total 8-week program, compared with only 7 out of 26 (27%) in the control group. The repeated-model analyses showed no significant change between the two interventions for ADHD symptoms and functionality levels over time. The mean difference in ADHD symptoms between TEAMS versus standard treatment at posttreatment was 2.18 points (95% confidence interval - 8.62 to 13.0; trial sequential analysis-adjusted confidence interval - 19.3 to 23.7). Trial registration Clinical Trials identifier: NCT01918436 (Retrospectively registered). Registered on 7 August 2013.}, } @article {pmid29884208, year = {2018}, author = {Zouei, N and Shojaee, S and Mohebali, M and Keshavarz, H}, title = {The association of latent toxoplasmosis and level of serum testosterone in humans.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {365}, pmid = {29884208}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Enzyme-Linked Immunosorbent Assay ; Female ; Humans ; Male ; Middle Aged ; Testosterone/*blood ; Toxoplasmosis/*blood ; Young Adult ; }, abstract = {OBJECTIVES: Latent toxoplasmosis modifies various hormones and behaviors in infected hosts and possibly involves in etiology of different neurologic and psychiatric disorders. The aim of the current study was to assess possible associations between latent toxoplasmosis and testosterone concentration in Toxoplasma infected and free subjects. Briefly, 18-49 year-old participated in the study. After collected blood samples, sera were analyzed for the detection of anti-Toxoplasma IgG antibody. Totally, 76 positive sera were selected as study group (38 from men and 38 from women) and a same number of negative sera as control group.

RESULTS: Comparison of testosterone concentrations and control groups showed that testosterone concentration in study group was higher than that in control group with statistically significant difference (P = 0.024 and P = 0.043 for men and women, respectively). Significant differences were found in testosterone concentrations and anti-Toxoplasma IgG antibody levels in study and control groups (P < 0.05). Toxoplasmosis can affect the mean concentration of serum testosterone in human. Alteration of testosterone during latent toxoplasmosis can result in alterations in behavioral, physiologic and immunological parameters in long time.}, } @article {pmid29884203, year = {2018}, author = {Thomas, M and Schwartz, R}, title = {A method for efficient Bayesian optimization of self-assembly systems from scattering data.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {65}, pmid = {29884203}, issn = {1752-0509}, support = {T32EB009403//National Institute of Biomedical Imaging and Bioengineering/ ; R21 CA216452/CA/NCI NIH HHS/United States ; T32 EB009403/EB/NIBIB NIH HHS/United States ; R21CA216452//National Cancer Institute/ ; GBMF4554 #4100070287//Pennsylvania Department of Health/ ; }, abstract = {BACKGROUND: The ability of collections of molecules to spontaneously assemble into large functional complexes is central to all cellular processes. Using the viral capsid as a model system for complicated macro-molecular assembly, we develop methods for probing fine details of the process by learning kinetic rate parameters consistent with experimental measures of assembly. We have previously shown that local rule based stochastic simulation methods in conjunction with bulk indirect experimental data can meaningfully constrain the space of possible assembly trajectories and allow inference of experimentally unobservable features of the real system.

RESULTS: In the present work, we introduce a new Bayesian optimization framework using multi-Gaussian process model regression. We also extend our prior work to encompass small-angle X-ray/neutron scattering (SAXS/SANS) as a possibly richer experimental data source than the previously used static light scattering (SLS). Method validation is based on synthetic experiments generated using protein data bank (PDB) structures of cowpea chlorotic mottle virus. We also apply the same approach to computationally cheaper differential equation based simulation models.

CONCLUSIONS: We present a flexible approach for the global optimization of computationally costly objective functions associated with dynamic, multidimensional models. When applied to the stochastic viral capsid system, our method outperforms a current state of the art black box solver tailored for use with noisy objectives. Our approach also has wide applicability to general stochastic optimization problems.}, } @article {pmid29884143, year = {2018}, author = {Janssen, R and Andersson, E and Betnér, E and Bijl, S and Fowler, W and Höök, L and Leyhr, J and Mannelqvist, A and Panara, V and Smith, K and Tiemann, S}, title = {Embryonic expression patterns and phylogenetic analysis of panarthropod sox genes: insight into nervous system development, segmentation and gonadogenesis.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {88}, pmid = {29884143}, issn = {1471-2148}, support = {621-2011-4703//Vetenskapsrådet/International ; }, mesh = {Animals ; Arthropods/classification/*embryology/*genetics ; Body Patterning/*genetics ; Drosophila melanogaster/genetics ; Embryo, Nonmammalian/metabolism ; Female ; Gene Expression Regulation, Developmental ; *Genes, Insect ; Gonads/*embryology ; Male ; Nervous System/*embryology ; Organogenesis/genetics ; *Phylogeny ; SOX Transcription Factors/*genetics ; }, abstract = {BACKGROUND: Sox (Sry-related high-mobility-group box) genes represent important factors in animal development. Relatively little, however, is known about the embryonic expression patterns and thus possible function(s) of Sox genes during ontogenesis in panarthropods (Arthropoda+Tardigrada+Onychophora). To date, studies have been restricted exclusively to higher insects, including the model system Drosophila melanogaster, with no comprehensive data available for any other arthropod group, or any tardigrade or onychophoran.

RESULTS: This study provides a phylogenetic analysis of panarthropod Sox genes and presents the first comprehensive analysis of embryonic expression patterns in the flour beetle Tribolium castaneum (Hexapoda), the pill millipede Glomeris marginata (Myriapoda), and the velvet worm, Euperipatoides kanangrensis (Onychophora). 24 Sox genes were identified and investigated: 7 in Euperipatoides, 8 in Glomeris, and 9 in Tribolium. Each species possesses at least one ortholog of each of the five expected Sox gene families, B, C, D, E, and F, many of which are differentially expressed during ontogenesis.

CONCLUSION: Sox gene expression (and potentially function) is highly conserved in arthropods and their closest relatives, the onychophorans. Sox B, C and D class genes appear to be crucial for nervous system development, while the Sox B genes Dichaete (D) and Sox21b likely play an additional conserved role in panarthropod segmentation. The Sox B gene Sox21a likely has a conserved function in foregut and Malpighian tubule development, at least in Hexapoda. The data further suggest that Sox D and E genes are involved in mesoderm differentiation, and that Sox E genes are involved in gonadal development. The new data expand our knowledge about the expression and implied function of Sox genes to Mandibulata (Myriapoda+Pancrustacea) and Panarthropoda (Arthropoda+Onychophora).}, } @article {pmid29884134, year = {2018}, author = {Keller, M and , and Simm, S}, title = {The coupling of transcriptome and proteome adaptation during development and heat stress response of tomato pollen.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {447}, pmid = {29884134}, issn = {1471-2164}, support = {SFB902//Deutsche Forschungsgemeinschaft/ ; 289220//EU / Marie Curie/ ; }, mesh = {Adaptation, Physiological/*genetics ; *Gene Expression Profiling ; Heat-Shock Response/*genetics ; Lycopersicon esculentum/genetics/growth & development/metabolism/*physiology ; Pollen/genetics/growth & development/metabolism/*physiology ; *Proteomics ; }, abstract = {BACKGROUND: Pollen development is central for plant reproduction and is assisted by changes of the transcriptome and proteome. At the same time, pollen development and viability is largely sensitive to stress, particularly to elevated temperatures. The transcriptomic and proteomic changes during pollen development and of different stages in response to elevated temperature was targeted to define the underlying molecular principles.

RESULTS: The analysis of the transcriptome and proteome of Solanum lycopersicum pollen at tetrad, post-meiotic and mature stage before and after heat stress yielded a decline of the transcriptome but an increase of the proteome size throughout pollen development. Comparison of the transcriptome and proteome led to the discovery of two modes defined as direct and delayed translation. Here, genes of distinct functional processes are under the control of direct and delayed translation. The response of pollen to elevated temperature occurs rather at proteome, but not as drastic at the transcriptome level. Heat shock proteins, proteasome subunits, ribosomal proteins and eukaryotic initiation factors are most affected. On the example of heat shock proteins we demonstrate a decoupling of transcript and protein levels as well as a distinct regulation between the developmental stages.

CONCLUSIONS: The transcriptome and proteome of developing pollen undergo drastic changes in composition and quantity. Changes at the proteome level are a result of two modes assigned as direct and delayed translation. The response of pollen to elevated temperature is mainly regulated at the proteome level, whereby proteins related to synthesis and degradation of proteins are most responsive and might play a central role in the heat stress response of pollen.}, } @article {pmid29884131, year = {2018}, author = {Zafra, A and Castro, AJ and Alché, JD}, title = {Identification of novel superoxide dismutase isoenzymes in the olive (Olea europaea L.) pollen.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {114}, pmid = {29884131}, issn = {1471-2229}, support = {BFU2016-77243-P//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; RTC-2016-4824-2//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; RTC-2015-4181-2//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; BFU2011-22779//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; 201540E065//Consejo Superior de Investigaciones Científicas/ ; 201840E055//Consejo Superior de Investigaciones Científicas/ ; P2010-AGR6274//Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía/ ; P2011-CVI-7487//Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía/ ; }, mesh = {Allergens/genetics/metabolism ; Blotting, Western ; Isoenzymes/genetics/*metabolism ; Mass Spectrometry ; Microscopy, Electron, Transmission ; Olea/*enzymology/genetics ; Plant Proteins/genetics/*metabolism ; Pollen/*enzymology/metabolism/ultrastructure ; Superoxide Dismutase/genetics/*metabolism ; Superoxide Dismutase-1/genetics/metabolism ; }, abstract = {BACKGROUND: Among antioxidant enzymes, the superoxide dismutase (SOD) family is a major actor in catalysing the disproportionation of superoxide. Apart from its role as antioxidant, these enzymes have a role in cell signalling, and Cu,Zn-SOD proteins are also major pollen allergens. In order to deepen our understanding of the SOD isoenzymes present in olive pollen and to analyse the molecular variability of the pollen Cu,Zn-SOD family, we carried out biochemical, transcriptomic and localization studies of pollen grains from different olive cultivars and other allergenic species.

RESULTS: Olive pollen showed a high rate of total SOD activity in all cultivars assayed, which did not correlate with pollen viability. Mass spectrometry analysis together with activity assays and Western blotting experiments enabled us to identify new forms of Cu,Zn-SOD enzyme (including chloroplastidic and peroxisomal forms) as well as differentially expressed Mn-, Fe- and Cu,Zn-SOD isoenzymes among the pollen of different olive cultivars and allergenic species. Ultrastructural localization of Cu,Zn-SOD revealed its plastidial localization in the pollen grain. We also identified the occurrence of a shorter form of one of the cytosolic Cu,Zn-SOD enzymes, likely as the result of alternative splicing. This shorter enzyme showed lower SOD activity as compared to the full length form.

CONCLUSIONS: The presence of multiple SOD isoenzymes in the olive pollen could be related to the need of finely tuning the ROS metabolism during the transition from its quiescent condition at maturity to a highly metabolically active state at germination.}, } @article {pmid29884129, year = {2018}, author = {Heinze, S and Kornberger, P and Grätz, C and Schwarz, WH and Zverlov, VV and Liebl, W}, title = {Transmating: conjugative transfer of a new broad host range expression vector to various Bacillus species using a single protocol.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {56}, pmid = {29884129}, issn = {1471-2180}, abstract = {BACKGROUND: The genus Bacillus includes a great variety of species with potential applications in biotechnology. While species such as B. subtilis or B. licheniformis are well-known and used to provide various products at industrial scale, other Bacillus species are less characterized and are not yet used in commercial processes. One reason for this is the fact that genetic manipulation of new isolates is usually complicated with conventional techniques which have to be adapted to each new strain. Even in well-established strains, the available transformation protocols often suffer from low efficiencies.

RESULTS: In this paper, we provide a new broad host range E. coli/Bacillus shuttle vector, named pBACOV (Bacillus conjugation vector), that can be efficiently transferred to various Bacillus species using a single protocol. A variant of pBACOV carrying the sfGFP gene was successfully transferred to eight different species from the genus Bacillus and to one Paenibacillus species using triparental conjugation ("transmating"). This was achieved using a single protocol and worked for nine out of eleven tested acceptor species. The transmating procedure was used to test expression of the heterologous reporter gene sfGFP under control of the PaprE-promoter from B. subtilis in several Bacillus species in parallel. Expression of sfGFP was found in eight out of nine transmates. For several of the tested species, this is the first report of a method for genetic modification and heterologous gene expression. The expression level, analyzed by measuring the relative sfGFP-fluorescence normalized to the cell density of the cultures, was highest in B. mojavensis.

CONCLUSIONS: The new shuttle vector pBACOV can be transferred to many different Bacillus and Paenibacillus species using a simple and efficient transmating protocol. It is a versatile tool facilitating the application of recombinant DNA technology in new as well as established strains, or selection of an ideal host for heterologous gene expression from a multitude of strains. This paves the way for the genetic modification and biotechnological exploitation of the broad diversity of species of Bacillus and related genera as well as different strains from these species.}, } @article {pmid29884128, year = {2018}, author = {Li, Y and Liu, G and Zhang, J and Zhong, X and He, Z}, title = {Identification of key genes in human airway epithelial cells in response to respiratory pathogens using microarray analysis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {58}, pmid = {29884128}, issn = {1471-2180}, abstract = {BACKGROUND: Airway epithelium is the primary target for pathogens. It functions not only as a mechanical barrier, but also as an important sentinel of the innate immune system. However, the interactions and processes between host airway epithelium and pathogens are not fully understood.

RESULTS: In this study, we identified responses of the human airway epithelium cells to respiratory pathogen infection. We retrieved three mRNA expression microarray datasets from the Gene Expression Omnibus database, and identified 116 differentially expressed genes common to all three datasets. Gene functional annotations were performed using Gene Ontology and pathway analyses. Using protein-protein interaction network analysis and text mining, we identified a subset of genes functioned as a group and associated with infection, inflammation, tissue adhesion, and receptor internalization in infected epithelial cells. These genes were further identified in BESE-2B cells in response to Talaromyces marneffei by Real-Time quantitative PCR (qRT-PCR). In addition, we performed an in silico prediction of microRNA-target interactions and examined our findings.

CONCLUSIONS: Using bioinformatics analysis, we identified several genes that may serve as biomarkers for the diagnosis or the surveillance of early respiratory tract infection, and identified additional genes and miRNAs that warrant further fundamental experimental research.}, } @article {pmid29884127, year = {2018}, author = {Kalule, JB and Keddy, KH and Nicol, MP}, title = {Characterisation of STEC and other diarrheic E. coli isolated on CHROMagar™STEC at a tertiary referral hospital, Cape Town.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {55}, pmid = {29884127}, issn = {1471-2180}, abstract = {BACKGROUND: Shiga toxin producing E. coli (STEC) is an emerging zoonotic pathogen that can cause acute renal failure, especially in children. Clinical microbiology laboratories may fail to detect STEC and other diarrhoeic E. coli unless purposive rigorous screening procedures are followed using appropriate diagnostic technology; CHROMagar™STEC has rarely been used for isolation of African diarrhoeic E. coli hence characteristics of isolates on this medium are not yet fully understood. This study aimed to determine the prevalence and characteristics of STEC and other diarrhoeic E. coli isolated on CHROMagar™STEC from stool samples submitted to the microbiology laboratory of a South African public sector tertiary care hospital.

RESULTS: In total, 733 stool samples were tested. Of these, 4.5% (33/733) possessed diarrhoeic E. coli. Of the diarrheic E. coli, 5/33 (15.2%) were STEC, 15/33 (45.5%) EAggEC, 6/33 (18.2%) atypical EPEC, 5/33 (15.2%) typical EPEC, and 1/33 (3%) DAEC. None of the STEC isolates had been identified by routine testing (based on using sorbitol media to test for E. coli O157: H7 strains and not the other STEC) in the laboratory. Of the 33 strains, 55% (95% CI = 40.8-72.7) showed resistance to ampicillin.

CONCLUSIONS: CHROMagar™STEC enabled detection of tellurite - resistant diarrhoeic E. coli that would be missed using routine methods. Further studies are needed to determine the proportion and characteristics of those which might have been missed using this approach.}, } @article {pmid29884125, year = {2018}, author = {Wang, Y and Yang, HM and Cao, W and Li, YB and Wang, ZY}, title = {Deep sequencing identification of miRNAs in pigeon ovaries illuminated with monochromatic light.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {446}, pmid = {29884125}, issn = {1471-2164}, support = {31702155//the National Science Foundation for Young Scientists of China/ ; }, mesh = {Animals ; *Columbidae ; Female ; Gene Ontology ; *High-Throughput Nucleotide Sequencing ; *Light ; MicroRNAs/*genetics ; Ovary/*metabolism/physiology/radiation effects ; Oviposition/genetics/radiation effects ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: The use of light of different wavelengths has grown popular in the poultry industry. An optimum wavelength is believed to improve pigeon egg production, but little is known about the role of microRNAs (miRNAs) in the effects of monochromatic light on ovarian pigeon function. Herein, we harvested ovaries from pigeons reared under monochromatic light of different wavelength and performed deep sequencing on various tissues using an Illumina Solexa high-throughput instrument.

RESULTS: We obtained 66,148,548, 67,873,805, and 71,661,771 clean reads from ovaries of pigeons reared under red light (RL), blue light (BL), and white light (WL), respectively. We identified 1917 known miRNAs in nine libraries, of which 524 were novel. Three and five differentially expressed miRNAs were identified in BL vs. WL and RL vs. WL groups, respectively. Quantitative reverse transcription PCR was used to validate differentially expressed miRNAs (miR-200, miR-122, and miR-205b). In addition, 5824 target genes were annotated as differentially expressed miRNAs, most of which are involved in reproductive pathways including oestrogen signalling, cell cycle, and oocyte maturation. Notably, ovarian miR-205b expression was significantly negatively correlated with its target 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1).

CONCLUSIONS: miRNA-mRNA network analysis suggests that miR-205b targeting of HSD11B1 plays a key role in the effects of monochromatic light on pigeon egg production. These findings indicate that monochromatic light shortens the oviposition interval of pigeons, which may be useful for egg production and pigeon breeding.}, } @article {pmid29884124, year = {2018}, author = {Milner, MJ and Howells, RM and Craze, M and Bowden, S and Graham, N and Wallington, EJ}, title = {A PSTOL-like gene, TaPSTOL, controls a number of agronomically important traits in wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {115}, pmid = {29884124}, issn = {1471-2229}, mesh = {Edible Grain/growth & development/metabolism ; Flowers/growth & development/metabolism ; Genes, Plant/*genetics/physiology ; Phosphates/metabolism ; Quantitative Trait, Heritable ; Sequence Analysis, DNA ; Triticum/*genetics/growth & development ; }, abstract = {BACKGROUND: Phosphorus (P) is an essential macronutrient for plant growth, and is required in large quantities by elite varieties of crops to maintain yields. Approximately 70% of global cultivated land suffers from P deficiency, and it has recently been estimated that worldwide P resources will be exhausted by the end of this century, increasing the demand for crops more efficient in their P usage. A greater understanding of how plants are able to maintain yield with lower P inputs is, therefore, highly desirable to both breeders and farmers. Here, we clone the wheat (Triticum aestivum L.) homologue of the rice PSTOL gene (OsPSTOL), and characterize its role in phosphate nutrition plus other agronomically important traits.

RESULTS: TaPSTOL is a single copy gene located on the short arm of chromosome 5A, encoding a putative kinase protein, and shares a high level of sequence similarity to OsPSTOL. We re-sequenced TaPSTOL from 24 different wheat accessions and (3) three T. durum varieties. No sequence differences were detected in 26 of the accessions, whereas two indels were identified in the promoter region of one of the durum wheats. We characterised the expression of TaPSTOL under different P concentrations and demonstrated that the promoter was induced in root tips and hairs under P limiting conditions. Overexpression and RNAi silencing of TaPSTOL in transgenic wheat lines showed that there was a significant effect upon root biomass, flowering time independent of P treatment, tiller number and seed yield, correlating with the expression of TaPSTOL. However this did not increase PUE as elevated P concentration in the grain did not correspond to increased yields.

CONCLUSIONS: Manipulation of TaPSTOL expression in wheat shows it is responsible for many of the previously described phenotypic advantages as OsPSTOL except yield. Furthermore, we show TaPSTOL contributes to additional agronomically important traits including flowering time and grain size. Analysis of TaPSTOL sequences from a broad selection of wheat varieties, encompassing 91% of the genetic diversity in UK bread wheat, showed that there is very little genetic variation in this gene, which would suggest that this locus may have been under high selection pressure.}, } @article {pmid29884123, year = {2018}, author = {Tirumalai, MR and Stepanov, VG and Wünsche, A and Montazari, S and Gonzalez, RO and Venkateswaran, K and Fox, GE}, title = {Bacillus safensis FO-36b and Bacillus pumilus SAFR-032: a whole genome comparison of two spacecraft assembly facility isolates.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {57}, pmid = {29884123}, issn = {1471-2180}, abstract = {BACKGROUND: Bacillus strains producing highly resistant spores have been isolated from cleanrooms and space craft assembly facilities. Organisms that can survive such conditions merit planetary protection concern and if that resistance can be transferred to other organisms, a health concern too. To further efforts to understand these resistances, the complete genome of Bacillus safensis strain FO-36b, which produces spores resistant to peroxide and radiation was determined. The genome was compared to the complete genome of B. pumilus SAFR-032, and the draft genomes of B. safensis JPL-MERTA-8-2 and the type strain B. pumilus ATCC7061T. Additional comparisons were made to 61 draft genomes that have been mostly identified as strains of B. pumilus or B. safensis.

RESULTS: The FO-36b gene order is essentially the same as that in SAFR-032 and other B. pumilus strains. The annotated genome has 3850 open reading frames and 40 noncoding RNAs and riboswitches. Of these, 307 are not shared by SAFR-032, and 65 are also not shared by MERTA and ATCC7061T. The FO-36b genome has ten unique open reading frames and two phage-like regions, homologous to the Bacillus bacteriophage SPP1 and Brevibacillus phage Jimmer1. Differing remnants of the Jimmer1 phage are found in essentially all B. safensis / B. pumilus strains. Seven unique genes are part of these phage elements. Whole Genome Phylogenetic Analysis of the B. pumilus, B. safensis and other Firmicutes genomes, separate them into three distinct clusters. Two clusters are subgroups of B. pumilus while one houses all the B. safensis strains. The Genome-genome distance analysis and a phylogenetic analysis of gyrA sequences corroborated these results.

CONCLUSIONS: It is not immediately obvious that the presence or absence of any specific gene or combination of genes is responsible for the variations in resistance seen. It is quite possible that distinctions in gene regulation can alter the expression levels of key proteins thereby changing the organism's resistance properties without gain or loss of a particular gene. What is clear is that phage elements contribute significantly to genome variability. Multiple genome comparison indicates that many strains named as B. pumilus likely belong to the B. safensis group.}, } @article {pmid29884119, year = {2018}, author = {Hawkins, MTR and Culligan, RR and Frasier, CL and Dikow, RB and Hagenson, R and Lei, R and Louis, EE}, title = {Genome sequence and population declines in the critically endangered greater bamboo lemur (Prolemur simus) and implications for conservation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {445}, pmid = {29884119}, issn = {1471-2164}, mesh = {Animals ; *Conservation of Natural Resources ; *Endangered Species ; Genome, Mitochondrial/genetics ; Genome, Plant/*genetics ; Genomics ; Lemuridae/*genetics/growth & development ; Polymorphism, Single Nucleotide ; Population Dynamics ; Sequence Analysis ; }, abstract = {BACKGROUND: The greater bamboo lemur (Prolemur simus) is a member of the Family Lemuridae that is unique in their dependency on bamboo as a primary food source. This Critically Endangered species lives in small forest patches in eastern Madagascar, occupying a fraction of its historical range. Here we sequence the genome of the greater bamboo lemur for the first time, and provide genome resources for future studies of this species that can be applied across its distribution.

RESULTS: Following whole genome sequencing of five individuals we identified over 152,000 polymorphic single nucleotide variants (SNVs), and evaluated geographic structuring across nearly 19 k SNVs. We characterized a stronger signal associated with a north-south divide than across elevations for our limited samples. We also evaluated the demographic history of this species, and infer a dramatic population crash. This species had the largest effective population size (estimated between ~ 900,000 to one million individuals) between approximately 60,000-90,000 years before present (ybp), during a time in which global climate change affected terrestrial mammals worldwide. We also note the single sample from the northern portion of the extant range had the largest effective population size around 35,000 ybp.

CONCLUSIONS: From our whole genome sequencing we recovered an average genomic heterozygosity of 0.0037%, comparable to other lemurs. Our demographic history reconstructions recovered a probable climate-related decline (60-90,000 ybp), followed by a second population decrease following human colonization, which has reduced the species to a census size of approximately 1000 individuals. The historical distribution was likely a vast portion of Madagascar, minimally estimated at 44,259 km2, while the contemporary distribution is only ~ 1700 km2. The decline in effective population size of 89-99.9% corresponded to a vast range retraction. Conservation management of this species is crucial to retain genetic diversity across the remaining isolated populations.}, } @article {pmid29884116, year = {2018}, author = {Hadigol, M and Khiabanian, H}, title = {MERIT reveals the impact of genomic context on sequencing error rate in ultra-deep applications.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {219}, pmid = {29884116}, issn = {1471-2105}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; S10 OD012346/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: Rapid progress in high-throughput sequencing (HTS) and the development of novel library preparation methods have improved the sensitivity of detecting mutations in heterogeneous samples, specifically in high-depth (> 500×) clinical applications. However, HTS methods are bounded by their technical and theoretical limitations and sequencing errors cannot be completely eliminated. Comprehensive quantification of the background noise can highlight both the efficiency and the limitations of any HTS methodology, and help differentiate true mutations at low abundance from artifacts.

RESULTS: We introduce MERIT (Mutation Error Rate Inference Toolkit), designed for in-depth quantification of erroneous substitutions and small insertions and deletions. MERIT incorporates an all-inclusive variant caller and considers genomic context, including the nucleotides immediately at 5 'and 3 ', thereby establishing error rates for 96 possible substitutions as well as four single-base and 16 double-base indels. We applied MERIT to ultra-deep sequencing data (1,300,000 ×) obtained from the amplification of multiple clinically relevant loci, and showed a significant relationship between error rates and genomic contexts. In addition to observing significant difference between transversion and transition rates, we identified variations of more than 100-fold within each error type at high sequencing depths. For instance, T >G transversions in trinucleotide GTCs occurred 133.5 ± 65.9 more often than those in ATAs. Similarly, C >T transitions in GCGs were observed at 73.8 ± 10.5 higher rate than those in TCTs. We also devised an in silico approach to determine the optimal sequencing depth, where errors occur at rates similar to those of expected true mutations. Our analyses showed that increasing sequencing depth might improve sensitivity for detecting some mutations based on their genomic context. For example, T >G rate of error in GTCs did not change when sequenced beyond 10,000 ×; in contrast, T >G rate in TTAs consistently improved even at above 500,000 ×.

CONCLUSIONS: Our results demonstrate significant variation in nucleotide misincorporation rates, and suggest that genomic context should be considered for comprehensive profiling of specimen-specific and sequencing artifacts in high-depth assays. This data provide strong evidence against assigning a single allele frequency threshold to call mutations, for it can result in substantial false positive as well as false negative variants, with important clinical consequences.}, } @article {pmid29884114, year = {2018}, author = {Gong, W and Kwak, IY and Pota, P and Koyano-Nakagawa, N and Garry, DJ}, title = {DrImpute: imputing dropout events in single cell RNA sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {220}, pmid = {29884114}, issn = {1471-2105}, support = {R01 HL122576/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: The single cell RNA sequencing (scRNA-seq) technique begin a new era by allowing the observation of gene expression at the single cell level. However, there is also a large amount of technical and biological noise. Because of the low number of RNA transcriptomes and the stochastic nature of the gene expression pattern, there is a high chance of missing nonzero entries as zero, which are called dropout events.

RESULTS: We develop DrImpute to impute dropout events in scRNA-seq data. We show that DrImpute has significantly better performance on the separation of the dropout zeros from true zeros than existing imputation algorithms. We also demonstrate that DrImpute can significantly improve the performance of existing tools for clustering, visualization and lineage reconstruction of nine published scRNA-seq datasets.

CONCLUSIONS: DrImpute can serve as a very useful addition to the currently existing statistical tools for single cell RNA-seq analysis. DrImpute is implemented in R and is available at https://github.com/gongx030/DrImpute .}, } @article {pmid29883774, year = {2018}, author = {Mao, D and Okada, BK and Wu, Y and Xu, F and Seyedsayamdost, MR}, title = {Recent advances in activating silent biosynthetic gene clusters in bacteria.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {156-163}, pmid = {29883774}, issn = {1879-0364}, support = {DP2 AI124786/AI/NIAID NIH HHS/United States ; }, } @article {pmid29883661, year = {2018}, author = {McConnell, AM and Mito, JK and Ablain, J and Dang, M and Formichella, L and Fisher, DE and Zon, LI}, title = {Neural crest state activation in NRAS driven melanoma, but not in NRAS-driven melanocyte expansion.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29883661}, issn = {1095-564X}, support = {T32 HL007627/HL/NHLBI NIH HHS/United States ; R01 CA103846/CA/NCI NIH HHS/United States ; R01 HL048801/HL/NHLBI NIH HHS/United States ; R01 AR043369/AR/NIAMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, abstract = {NRAS mutations are frequently found in many deadly malignancies and are the second most common oncogene driving malignant melanoma. Here, we generate a rapid transient transgenic zebrafish model of NRASQ61R-mutant melanoma. These fish develop extensive melanocytic proliferation in approximately 4 weeks. The majority of these lesions do not engraft upon transplantation and lack overt histologic features of malignancy. Our previous work demonstrated that activation of a neural crest cell transcriptional program is a key initiating event in zebrafish BRAF/p53-driven melanomas using the fluorescent reporter crestin:EGFP. By 8-12 weeks of age, some lesions progress to malignant melanoma and have cytologic atypia, destructive tissue invasion, and express neural crest progenitor markers, including crestin:EGFP. Our studies demonstrate that NRASQ61R induces extensive melanocyte expansion, which arise during zebrafish development and lack a transformed phenotype. These early lesions are highly predisposed to reactivate a neural crest progenitor fate and form malignant melanomas.}, } @article {pmid29883660, year = {2018}, author = {Riddle, MR and Boesmans, W and Caballero, O and Kazwiny, Y and Tabin, CJ}, title = {Morphogenesis and motility of the Astyanax mexicanus gastrointestinal tract.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {285-296}, pmid = {29883660}, issn = {1095-564X}, support = {F32 DK108495/DK/NIDDK NIH HHS/United States ; R01 HD089934/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Characiformes/*embryology ; Enteric Nervous System/embryology ; Feeding Behavior/*physiology ; Gastrointestinal Motility/*physiology ; Gastrointestinal Tract/*embryology/innervation ; Morphogenesis/*physiology ; Muscle, Smooth/embryology ; }, abstract = {Through the course of evolution, the gastrointestinal (GI) tract has been modified to maximize nutrient absorption, forming specialized segments that are morphologically and functionally distinct. Here we show that the GI tract of the Mexican tetra, Astyanax mexicanus, has distinct regions, exhibiting differences in morphology, motility, and absorption. We found that A. mexicanus populations adapted for life in subterranean caves exhibit differences in the GI segments compared to those adapted to surface rivers. Cave-adapted fish exhibit bi-directional churning motility in the stomach region that is largely absent in river-adapted fish. We investigated how this motility pattern influences intestinal transit of powdered food and live prey. We found that powdered food is more readily emptied from the cavefish GI tract. In contrast, the transit of live rotifers from the stomach region to the midgut occurs more slowly in cavefish compared to surface fish, consistent with the presence of churning motility. Differences in intestinal motility and transit likely reflect adaptation to unique food sources available to post-larval A. mexicanus in the cave and river environments. We found that cavefish grow more quickly than surface fish when fed ad libitum, suggesting that altered GI function may aid in nutrient consumption or absorption. We did not observe differences in enteric neuron density or smooth muscle organization between cavefish and surface fish. Altered intestinal motility in cavefish could instead be due to changes in the activity or patterning of the enteric nervous system. Exploring this avenue will lead to a better understanding of how the GI tract evolves to maximize energy assimilation from novel food sources.}, } @article {pmid29883659, year = {2018}, author = {Xiong, S and Krishnan, J and Peuß, R and Rohner, N}, title = {Early adipogenesis contributes to excess fat accumulation in cave populations of Astyanax mexicanus.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {297-304}, doi = {10.1016/j.ydbio.2018.06.003}, pmid = {29883659}, issn = {1095-564X}, mesh = {*Adaptation, Physiological ; Adipogenesis/*physiology ; Animals ; Caves ; Characiformes/*physiology ; Intra-Abdominal Fat/*physiology ; }, abstract = {Cavefish populations of Astyanax mexicanus have increased body fat compared to surface fish populations of the same species when fed ad libitum in the laboratory. We have previously shown that some cavefish populations display hyperphagia (elevated appetite) to increase food consumption, fat deposition and starvation resistance. However, not all cavefish populations display hyperphagia, yet all previously tested cavefish display elevated body fat levels. Here we have extended this analysis by focusing on visceral fat acquisition in three independently derived cavefish populations. We show that cavefish from two independently derived cavefish populations (Pachón and Tinaja) display increased amounts of visceral adipose tissue (VAT) due to hypertrophy of visceral adipocytes while Molino cavefish display hypertrophy but only slightly elevated VAT levels compared to surface fish. Furthermore, we show that Pachón and Tinaja cavefish develop increased VAT even when food intake is matched to surface fish, suggesting appetite independent mechanisms. We show that in the Pachón population, the differences in the visceral fat in adults correlates with changes in the timing of visceral development, making a developmental contribution likely. Visceral fat development in surface fish starts between 10 and 11 dpf, while in Pachón cavefish, visceral fat cells become visible as early as 8 dpf and develop significantly higher amounts of lipid droplets before surface fish start visceral fat accumulation. We further show that this developmental difference is unique to the Pachón cavefish population, while the Tinaja cavefish population - which displays hyperphagia - starts to develop visceral fat similar to surface fish. We suggest the differences in early adipogenesis in the Pachón population as an additional strategy of increased fat gain in cavefish to adapt to food scarcity.}, } @article {pmid29883658, year = {2018}, author = {Morris, JL and Cross, SJ and Lu, Y and Kadler, KE and Lu, Y and Dallas, SL and Martin, P}, title = {Live imaging of collagen deposition during skin development and repair in a collagen I - GFP fusion transgenic zebrafish line.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {4-11}, pmid = {29883658}, issn = {1095-564X}, support = {097791/Z/11/Z//Wellcome Trust/United Kingdom ; 110126/Z/15/Z//Wellcome Trust/United Kingdom ; R01 AR051517/AR/NIAMS NIH HHS/United States ; P01 AG039355/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Animals, Genetically Modified/embryology/genetics ; *Collagen Type I/biosynthesis/genetics ; *Green Fluorescent Proteins/biosynthesis/genetics ; Optical Imaging/*methods ; *Recombinant Fusion Proteins/biosynthesis/genetics ; *Skin/cytology/embryology ; *Zebrafish/embryology/genetics ; }, abstract = {Fibrillar collagen is a major component of many tissues but has been difficult to image in vivo using transgenic approaches because of problems associated with establishing cells and organisms that generate GFP-fusion collagens that can polymerise into functional fibrils. Here we have developed and characterised GFP and mCherry collagen-I fusion zebrafish lines with basal epidermal-specific expression. We use these lines to reveal the dynamic nature of collagen-I fibril deposition beneath the developing embryonic epidermis, as well as the repair of this collagen meshwork following wounding. Transmission electron microscope studies show that these transgenic lines faithfully reproduce the collagen ultrastructure present in wild type larval skin. During skin development we show that collagen I is deposited by basal epidermal cells initially in fine filaments that are largely randomly orientated but are subsequently aligned into a cross-hatch, orthogonal sub-epithelial network by embryonic day 4. Following skin wounding, we see that sub-epidermal collagen is re-established in the denuded domain, initially as randomly orientated wisps that subsequently become bonded to the undamaged collagen and aligned in a way that recapitulates developmental deposition of sub-epidermal collagen. Crossing our GFP-collagen line against one with tdTomato marking basal epidermal cell membranes reveals how much more rapidly wound re-epithelialisation occurs compared to the re-deposition of collagen beneath the healed epidermis. By use of other tissue specific drivers it will be possible to establish zebrafish lines to enable live imaging of collagen deposition and its remodelling in various other organs in health and disease.}, } @article {pmid29882597, year = {2018}, author = {Gallet, R and Froissart, R and Ravigné, V}, title = {Experimental demonstration of the impact of hard and soft selection regimes on polymorphism maintenance in spatially heterogeneous environments.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13513}, pmid = {29882597}, issn = {1558-5646}, abstract = {Predicting and managing contemporary adaption requires a proper understanding of the determinants of genetic variation. Spatial heterogeneity of the environment may stably maintain polymorphism when habitat contribution to the next generation can be considered independent of the degree of adaptation of local populations within habitats (i.e., under soft selection). In contrast, when habitats contribute proportionally to the mean fitness of the populations they host (hard selection), polymorphism is not expected to be maintained by selection. Although mathematically established decades ago, this prediction had never been demonstrated experimentally. Here, we provide an experimental test in which polymorphic populations of Escherichia coli growing in heterogeneous habitats were exposed to hard and soft selection regimes. As predicted by theory, polymorphism was preserved longer under soft selection. Complementary tests established that soft selection slowed fixation processes and could even protect polymorphism in the long term by providing a systematic advantage to rare genotypes.}, } @article {pmid29882586, year = {2018}, author = {Law, CJ and Mehta, RS}, title = {Carnivory maintains cranial dimorphism between males and females: Evidence for niche divergence in extant Musteloidea.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {9}, pages = {1950-1961}, doi = {10.1111/evo.13514}, pmid = {29882586}, issn = {1558-5646}, support = {//American Museum of Natural History/ ; //Field Museum/ ; //Division of Environmental Biology/ ; //American Society of Mammalogists/ ; //Society of Integrative & Comparative Biology/ ; //Society for the Study of Evolution/ ; }, abstract = {The evolution and maintenance of sexual dimorphism has long been attributed to sexual selection. Niche divergence, however, serves as an alternative but rarely tested selective pressure also hypothesized to drive phenotypic disparity between males and females. We reconstructed ancestral social systems and diet and used Ornstein-Uhlenbeck (OU) modeling approaches to test whether niche divergence is stronger than sexual selection in driving the evolution of sexual dimorphism in cranial size and bite force across extant Musteloidea. We found that multipeak OU models favored different dietary regimes over social behavior and that the greatest degree of cranial size and bite force dimorphism were found in terrestrial carnivores. Because competition for terrestrial vertebrate prey is greater than other dietary groups, increased cranial size and bite force dimorphism reduces dietary competition between the sexes. In contrast, neither dietary regime nor social system influenced the evolution of sexual dimorphism in cranial shape. Furthermore, we found that the evolution of sexual dimorphism in bite force is influenced by the evolution of sexual dimorphism in cranial size rather than cranial shape. Overall, our results highlight niche divergence as an important mechanism that maintains the evolution of sexual dimorphism in musteloids.}, } @article {pmid29882584, year = {2018}, author = {Teerikorpi, PE and Sirkiä, PM and Laaksonen, T}, title = {Ecological crossovers of sexual signaling in a migratory bird.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2038-2048}, doi = {10.1111/evo.13515}, pmid = {29882584}, issn = {1558-5646}, support = {//Biotieteiden ja Ympäristön Tutkimuksen Toimikunta/ ; //Emil Aaltosen Säätiö/ ; //Ella ja Georg Ehrnroothin Säätiö/ ; //Turun Yliopistosäätiö/ ; }, abstract = {Environmental shifts may induce sudden reversals in the relative quality or sexual attractiveness of mates (ecological crossovers) leading to non-directional sexual selection. Studies on such ecological crossovers induced by environmental shifts during the nonbreeding season are particularly rare. We studied the interactive effects between nonbreeding conditions and a male white wing patch on the breeding success of breeding pairs and the local survival of females in a migratory passerine population over a 32-year period. After dry winters, females paired with large-patched males were more likely to survive than those paired with small-patched males, and vice versa after moist winters. Moreover, after dry winters, large-patched males succeeded in attracting females that laid large clutches, while small-patched males bred with females that laid small clutches, and vice versa after moist winters. This phenomenon led to a difference in fledgling numbers only during years with dry winters and high precipitation during the breeding season. The selection on this male trait and its signaling value to females thus depended on a complex interaction between conditions both at the nonbreeding and breeding grounds. We show that it is important to consider conditions during the nonbreeding season when examining the effects of sexual ornaments on fitness.}, } @article {pmid29882067, year = {2018}, author = {Kuroda, M and Fujimoto, T and Murakami, M and Yamaha, E and Arai, K}, title = {Clonal reproduction assured by sister chromosome pairing in dojo loach, a teleost fish.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s10577-018-9581-4}, pmid = {29882067}, issn = {1573-6849}, support = {15H02457//Japan Society for the Promotion of Science/ ; 17J01971//Japan Society for the Promotion of Science/ ; }, abstract = {Wild-type dojo loach (Misgurnus anguillicaudatus) commonly reproduces bisexually as a gonochoristic diploid (2n = 50), but gynogenetically reproducing clonal diploid lines (2n = 50) exist in certain districts in Japan. Clones have been considered to develop from past hybridization event(s) between two genetically diverse groups, A and B, within the species. Fluorescence in situ hybridization analyses using the repetitive sequence "ManDra" as a probe clearly distinguished 25 chromosomes derived from group B out of a total of 50 diploid chromosomes of the clone, providing strong molecular cytogenetic evidence of its hybrid origin. In meiosis, diploid wild-type showed 25 bivalents, while diploid clones revealed 50 bivalents, indicating the presence of 100 chromosomes. In meiotic chromosome spreads in sex-reversed clonal males, ManDra signals were detected in 25 out of 50 bivalents, and only one out of two bivalents possessing major ribosomal RNA coding regions exhibited two positive ManDra signals. In clonal females, ManDra signals were detected in approximately 25 out of 50 bivalents. Thus, unreduced gametes should be generated by the pairing between sister chromosomes doubled from each ancestral chromosome from the different groups by premeiotic endomitosis. Sister chromosome pairing should assure production of unreduced isogenic clonal gametes due to the absence of the influence of recombination or crossing over.}, } @article {pmid29882066, year = {2018}, author = {Kretschmer, R and de Oliveira Furo, I and Gunski, RJ and Del Valle Garnero, A and Pereira, JC and O'Brien, PCM and Ferguson-Smith, MA and de Oliveira, EHC and de Freitas, TRO}, title = {Comparative chromosome painting in Columbidae (Columbiformes) reinforces divergence in Passerea and Columbea.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, pmid = {29882066}, issn = {1573-6849}, abstract = {Pigeons and doves (Columbiformes) are one of the oldest and most diverse extant lineages of birds. However, the karyotype evolution within Columbiformes remains unclear. To delineate the synteny-conserved segments and karyotypic differences among four Columbidae species, we used chromosome painting from Gallus gallus (GGA, 2n = 78) and Leucopternis albicollis (LAL, 2n = 68). Besides that, a set of painting probes for the eared dove, Zenaida auriculata (ZAU, 2n = 76), was generated from flow-sorted chromosomes. Chromosome painting with GGA and ZAU probes showed conservation of the first ten ancestral pairs in Z. auriculata, Columba livia, and Columbina picui, while in Leptotila verreauxi, fusion of the ancestral chromosomes 6 and 7 was observed. However, LAL probes revealed a complex reorganization of ancestral chromosome 1, involving paracentric and pericentric inversions. Because of the presence of similar intrachromosomal rearrangements in the chromosomes corresponding to GGA1q in the Columbidae and Passeriformes species but without a common origin, these results are consistent with the recent proposal of divergence within Neoaves (Passerea and Columbea). In addition, inversions in chromosome 2 were identified in C. picui and L. verreauxi. Thus, in four species of distinct genera of the Columbidae family, unique chromosomal rearrangements have occurred during karyotype evolution, confirming that despite conservation of the ancestral syntenic groups, these chromosomes have been modified by the occurrence of intrachromosomal rearrangements.}, } @article {pmid29881251, year = {2018}, author = {Allen, JM and LaFrance, R and Folk, RA and Johnson, KP and Guralnick, RP}, title = {aTRAM 2.0: An Improved, Flexible Locus Assembler for NGS Data.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318774546}, pmid = {29881251}, issn = {1176-9343}, abstract = {Massive strides have been made in technologies for collecting genome-scale data. However, tools for efficiently and flexibly assembling raw outputs into downstream analytical workflows are still nascent. aTRAM 1.0 was designed to assemble any locus from genome sequencing data but was neither optimized for efficiency nor able to serve as a single toolkit for all assembly needs. We have completely re-implemented aTRAM and redesigned its structure for faster read retrieval while adding a number of key features to improve flexibility and functionality. The software can now (1) assemble single- or paired-end data, (2) utilize both read directions in the database, (3) use an additional de novo assembly module, and (4) leverage new built-in pipelines to automate common workflows in phylogenomics. Owing to reimplementation of databasing strategies, we demonstrate that aTRAM 2.0 is much faster across all applications compared to the previous version.}, } @article {pmid29880819, year = {2018}, author = {Holmes, EC and Rambaut, A and Andersen, KG}, title = {Pandemics: spend on surveillance, not prediction.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {180-182}, doi = {10.1038/d41586-018-05373-w}, pmid = {29880819}, issn = {1476-4687}, support = {U19 AI135995/AI/NIAID NIH HHS/United States ; UL1 TR002550/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Animals, Wild/virology ; Communicable Diseases, Emerging/epidemiology/prevention & control/transmission/virology ; Congo/epidemiology ; Environmental Monitoring/economics ; Forecasting/*methods ; Hemorrhagic Fever, Ebola/economics/epidemiology/prevention & control/virology ; Humans ; Pandemics/economics/*prevention & control/*statistics & numerical data ; Population Surveillance/*methods ; Time Factors ; Trust ; Viruses/genetics/*isolation & purification ; World Health Organization ; Zoonoses/*epidemiology/*prevention & control/transmission/virology ; }, } @article {pmid29880795, year = {2018}, author = {Kemp, RS}, title = {North Korean disarmament: build technology and trust.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {367-369}, doi = {10.1038/d41586-018-05383-8}, pmid = {29880795}, issn = {1476-4687}, } @article {pmid29880725, year = {2018}, author = {Xiao, Y and Luo, M and Dolan, AE and Liao, M and Ke, A}, title = {Structure basis for RNA-guided DNA degradation by Cascade and Cas3.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {}, doi = {10.1126/science.aat0839}, pmid = {29880725}, issn = {1095-9203}, support = {R35 GM118174/GM/NIGMS NIH HHS/United States ; R01 GM102543/GM/NIGMS NIH HHS/United States ; }, mesh = {Actinobacteria/genetics/*metabolism ; Bacterial Proteins/*chemistry/genetics ; CRISPR-Associated Proteins/*chemistry/genetics ; Cryoelectron Microscopy ; DNA/*chemistry/genetics ; *DNA Breaks, Single-Stranded ; *DNA Fragmentation ; DNA Helicases/*chemistry/genetics ; Nucleic Acid Conformation ; Protein Conformation ; RNA, Guide/*chemistry/genetics ; }, abstract = {Type I CRISPR-Cas system features a sequential target-searching and degradation process on double-stranded DNA by the RNA-guided Cascade (CRISPR associated complex for antiviral defense) complex and the nuclease-helicase fusion enzyme Cas3, respectively. Here, we present a 3.7-angstrom-resolution cryo-electron microscopy (cryo-EM) structure of the Type I-E Cascade/R-loop/Cas3 complex, poised to initiate DNA degradation. Cas3 distinguishes Cascade conformations and only captures the R-loop-forming Cascade, to avoid cleaving partially complementary targets. Its nuclease domain recruits the nontarget strand (NTS) DNA at a bulged region for the nicking of single-stranded DNA. An additional 4.7-angstrom-resolution cryo-EM structure captures the postnicking state, in which the severed NTS retracts to the helicase entrance, to be threaded for adenosine 5'-triphosphate-dependent processive degradation. These snapshots form the basis for understanding RNA-guided DNA degradation in Type I-E CRISPR-Cas systems.}, } @article {pmid29880724, year = {2018}, author = {Stearns, LA and van der Veen, CJ}, title = {Friction at the bed does not control fast glacier flow.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6399}, pages = {273-277}, doi = {10.1126/science.aat2217}, pmid = {29880724}, issn = {1095-9203}, abstract = {The largest uncertainty in the ice sheet models used to predict future sea level rise originates from our limited understanding of processes at the ice/bed interface. Near glacier termini, where basal sliding controls ice flow, most predictive ice sheet models use a parameterization of sliding that has been theoretically derived for glacier flow over a hard bed. We find that this sliding relation does not apply to the 140 Greenland glaciers that we analyzed. There is no relationship between basal sliding and frictional stress at the glacier bed, contrary to theoretical predictions. There is a strong relationship between sliding speed and net pressure at the glacier bed. This latter finding is in agreement with earlier observations of mountain glaciers that have been largely overlooked by the glaciological community.}, } @article {pmid29880723, year = {2018}, author = {Imkeller, K and Scally, SW and Bosch, A and Martí, GP and Costa, G and Triller, G and Murugan, R and Renna, V and Jumaa, H and Kremsner, PG and Sim, BKL and Hoffman, SL and Mordmüller, B and Levashina, EA and Julien, JP and Wardemann, H}, title = {Antihomotypic affinity maturation improves human B cell responses against a repetitive epitope.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1358-1362}, doi = {10.1126/science.aar5304}, pmid = {29880723}, issn = {1095-9203}, support = {//CIHR/Canada ; }, mesh = {Antibodies, Protozoan/chemistry/genetics/*immunology ; Antibody Affinity/genetics/*immunology ; Antibody Formation/genetics/*immunology ; Antigens, Protozoan/chemistry/genetics/*immunology ; B-Lymphocytes/*immunology ; Epitopes, B-Lymphocyte/*immunology ; Humans ; Lymphocyte Activation ; Mutation ; Plasmodium falciparum/*immunology ; Protozoan Proteins/genetics/*immunology ; Repetitive Sequences, Nucleic Acid/genetics/immunology ; Selection, Genetic ; }, abstract = {Affinity maturation selects B cells expressing somatically mutated antibody variants with improved antigen-binding properties to protect from invading pathogens. We determined the molecular mechanism underlying the clonal selection and affinity maturation of human B cells expressing protective antibodies against the circumsporozoite protein of the malaria parasite Plasmodium falciparum (PfCSP). We show in molecular detail that the repetitive nature of PfCSP facilitates direct homotypic interactions between two PfCSP repeat-bound monoclonal antibodies, thereby improving antigen affinity and B cell activation. These data provide a mechanistic explanation for the strong selection of somatic mutations that mediate homotypic antibody interactions after repeated parasite exposure in humans. Our findings demonstrate a different mode of antigen-mediated affinity maturation to improve antibody responses to PfCSP and presumably other repetitive antigens.}, } @article {pmid29880716, year = {2018}, author = {Liu, JL and Zhao, M and Zhang, WQ and Huang, MY}, title = {Expansion of the IL1B gene family in the pig.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E5843-E5844}, pmid = {29880716}, issn = {1091-6490}, mesh = {Animals ; *Genetic Predisposition to Disease ; Humans ; Interleukin-1/*genetics ; Interleukin-1beta/genetics ; Polymorphism, Single Nucleotide ; Swine ; }, } @article {pmid29880715, year = {2018}, author = {Jones, KJ and Templet, S and Zemoura, K and Kuzniewska, B and Pena, FX and Hwang, H and Lei, DJ and Haensgen, H and Nguyen, S and Saenz, C and Lewis, M and Dziembowska, M and Xu, W}, title = {Rapid, experience-dependent translation of neurogranin enables memory encoding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5805-E5814}, pmid = {29880715}, issn = {1091-6490}, mesh = {Animals ; Fear/physiology ; Fragile X Mental Retardation Protein/metabolism ; Hippocampus/metabolism/physiology ; Male ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Neurogranin/*metabolism ; Neurons/metabolism/physiology ; Protein Biosynthesis/*physiology ; RNA, Messenger/metabolism ; }, abstract = {Experience induces de novo protein synthesis in the brain and protein synthesis is required for long-term memory. It is important to define the critical temporal window of protein synthesis and identify newly synthesized proteins required for memory formation. Using a behavioral paradigm that temporally separates the contextual exposure from the association with fear, we found that protein synthesis during the transient window of context exposure is required for contextual memory formation. Among an array of putative activity-dependent translational neuronal targets tested, we identified one candidate, a schizophrenia-associated candidate mRNA, neurogranin (Ng, encoded by the Nrgn gene) responding to novel-context exposure. The Ng mRNA was recruited to the actively translating mRNA pool upon novel-context exposure, and its protein levels were rapidly increased in the hippocampus. By specifically blocking activity-dependent translation of Ng using virus-mediated molecular perturbation, we show that experience-dependent translation of Ng in the hippocampus is required for contextual memory formation. We further interrogated the molecular mechanism underlying the experience-dependent translation of Ng, and found that fragile-X mental retardation protein (FMRP) interacts with the 3'UTR of the Nrgn mRNA and is required for activity-dependent translation of Ng in the synaptic compartment and contextual memory formation. Our results reveal that FMRP-mediated, experience-dependent, rapid enhancement of Ng translation in the hippocampus during the memory acquisition enables durable context memory encoding.}, } @article {pmid29880714, year = {2018}, author = {Vickers, AJ}, title = {Pharmacogenomics of antioxidant supplementation to prevent age-related macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5639}, pmid = {29880714}, issn = {1091-6490}, mesh = {*Antioxidants ; Dietary Supplements ; Humans ; Macular Degeneration ; *Pharmacogenetics ; }, } @article {pmid29880713, year = {2018}, author = {Vavvas, DG and Small, KW and Awh, C and Zanke, BW and Tibshirani, RJ and Kustra, R}, title = {Reply to Vickers: Pharmacogenetics and progression to neovascular age-related macular degeneration-Evidence supporting practice change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5640-E5641}, pmid = {29880713}, issn = {1091-6490}, mesh = {Angiogenesis Inhibitors ; Disease Progression ; Humans ; *Macular Degeneration ; *Pharmacogenetics ; Vascular Endothelial Growth Factor A ; }, } @article {pmid29880693, year = {2018}, author = {Dowtin, AL and Levia, DF}, title = {The power of persistence.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1142}, doi = {10.1126/science.360.6393.1142}, pmid = {29880693}, issn = {1095-9203}, } @article {pmid29880692, year = {2018}, author = {Ngo, TTM and Moufarrej, MN and Rasmussen, MH and Camunas-Soler, J and Pan, W and Okamoto, J and Neff, NF and Liu, K and Wong, RJ and Downes, K and Tibshirani, R and Shaw, GM and Skotte, L and Stevenson, DK and Biggio, JR and Elovitz, MA and Melbye, M and Quake, SR}, title = {Noninvasive blood tests for fetal development predict gestational age and preterm delivery.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1133-1136}, doi = {10.1126/science.aar3819}, pmid = {29880692}, issn = {1095-9203}, mesh = {Adult ; Blood Chemical Analysis/*methods ; Cell-Free Nucleic Acids/*blood ; Female ; *Fetal Development ; Fetal Monitoring/*methods ; *Gestational Age ; Humans ; Pilot Projects ; Pregnancy ; Premature Birth/*blood/*diagnosis ; Prenatal Care ; Young Adult ; }, abstract = {Noninvasive blood tests that provide information about fetal development and gestational age could potentially improve prenatal care. Ultrasound, the current gold standard, is not always affordable in low-resource settings and does not predict spontaneous preterm birth, a leading cause of infant death. In a pilot study of 31 healthy pregnant women, we found that measurement of nine cell-free RNA (cfRNA) transcripts in maternal blood predicted gestational age with comparable accuracy to ultrasound but at substantially lower cost. In a related study of 38 women (23 full-term and 15 preterm deliveries), all at elevated risk of delivering preterm, we identified seven cfRNA transcripts that accurately classified women who delivered preterm up to 2 months in advance of labor. These tests hold promise for prenatal care in both the developed and developing worlds, although they require validation in larger, blinded clinical trials.}, } @article {pmid29880691, year = {2018}, author = {Yu, X and Zhao, Z and Zheng, X and Zhou, J and Kong, W and Wang, P and Bai, W and Zheng, H and Zhang, H and Li, J and Liu, J and Wang, Q and Zhang, L and Liu, K and Yu, Y and Guo, X and Wang, J and Lin, Q and Wu, F and Ren, Y and Zhu, S and Zhang, X and Cheng, Z and Lei, C and Liu, S and Liu, X and Tian, Y and Jiang, L and Ge, S and Wu, C and Tao, D and Wang, H and Wan, J}, title = {A selfish genetic element confers non-Mendelian inheritance in rice.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1130-1132}, doi = {10.1126/science.aar4279}, pmid = {29880691}, issn = {1095-9203}, mesh = {Crosses, Genetic ; Evolution, Molecular ; *Genomic Instability ; Germ Cells, Plant ; Hybridization, Genetic ; Open Reading Frames/genetics ; Oryza/*genetics ; *Plant Infertility ; Pollen/genetics ; *Quantitative Trait Loci ; *Repetitive Sequences, Nucleic Acid ; }, abstract = {Selfish genetic elements are pervasive in eukaryote genomes, but their role remains controversial. We show that qHMS7, a major quantitative genetic locus for hybrid male sterility between wild rice (Oryza meridionalis) and Asian cultivated rice (O. sativa), contains two tightly linked genes [Open Reading Frame 2 (ORF2) and ORF3]. ORF2 encodes a toxic genetic element that aborts pollen in a sporophytic manner, whereas ORF3 encodes an antidote that protects pollen in a gametophytic manner. Pollens lacking ORF3 are selectively eliminated, leading to segregation distortion in the progeny. Analysis of the genetic sequence suggests that ORF3 arose first, followed by gradual functionalization of ORF2 Furthermore, this toxin-antidote system may have promoted the differentiation and/or maintained the genome stability of wild and cultivated rice.}, } @article {pmid29880690, year = {2018}, author = {Howard, SR and Avarguès-Weber, A and Garcia, JE and Greentree, AD and Dyer, AG}, title = {Numerical ordering of zero in honey bees.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1124-1126}, doi = {10.1126/science.aar4975}, pmid = {29880690}, issn = {1095-9203}, mesh = {Animals ; *Bees ; *Biological Evolution ; *Cognition ; *Mathematical Concepts ; }, abstract = {Some vertebrates demonstrate complex numerosity concepts-including addition, sequential ordering of numbers, or even the concept of zero-but whether an insect can develop an understanding for such concepts remains unknown. We trained individual honey bees to the numerical concepts of "greater than" or "less than" using stimuli containing one to six elemental features. Bees could subsequently extrapolate the concept of less than to order zero numerosity at the lower end of the numerical continuum. Bees demonstrated an understanding that parallels animals such as the African grey parrot, nonhuman primates, and even preschool children.}, } @article {pmid29880689, year = {2018}, author = {Gess, R and Ahlberg, PE}, title = {A tetrapod fauna from within the Devonian Antarctic Circle.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1120-1124}, doi = {10.1126/science.aaq1645}, pmid = {29880689}, issn = {1095-9203}, mesh = {Animals ; Antarctic Regions ; *Biological Evolution ; Fossils ; Jaw/anatomy & histology ; South Africa ; *Vertebrates/anatomy & histology ; }, abstract = {Until now, all known fossils of tetrapods (limbed vertebrates with digits) and near-tetrapods (such as Elpistostege, Tiktaalik, and Panderichthys) from the Devonian period have come from localities in tropical to subtropical paleolatitudes. Most are from Laurussia, a continent incorporating Europe, Greenland, and North America, with only one body fossil and one footprint locality from Australia representing the southern supercontinent Gondwana. Here we describe two previously unknown tetrapods from the Late Devonian (late Famennian) Gondwana locality of Waterloo Farm in South Africa, then located within the Antarctic Circle, which demonstrate that Devonian tetrapods were not restricted to warm environments and suggest that they may have been global in distribution.}, } @article {pmid29880688, year = {2018}, author = {Centola, D and Becker, J and Brackbill, D and Baronchelli, A}, title = {Experimental evidence for tipping points in social convention.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1116-1119}, doi = {10.1126/science.aas8827}, pmid = {29880688}, issn = {1095-9203}, mesh = {Humans ; Interpersonal Relations ; Minority Groups/*psychology ; Social Behavior ; *Social Change ; *Social Norms ; }, abstract = {Theoretical models of critical mass have shown how minority groups can initiate social change dynamics in the emergence of new social conventions. Here, we study an artificial system of social conventions in which human subjects interact to establish a new coordination equilibrium. The findings provide direct empirical demonstration of the existence of a tipping point in the dynamics of changing social conventions. When minority groups reached the critical mass-that is, the critical group size for initiating social change-they were consistently able to overturn the established behavior. The size of the required critical mass is expected to vary based on theoretically identifiable features of a social setting. Our results show that the theoretically predicted dynamics of critical mass do in fact emerge as expected within an empirical system of social coordination.}, } @article {pmid29880687, year = {2018}, author = {Otterstrom, NT and Behunin, RO and Kittlaus, EA and Wang, Z and Rakich, PT}, title = {A silicon Brillouin laser.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1113-1116}, doi = {10.1126/science.aar6113}, pmid = {29880687}, issn = {1095-9203}, abstract = {Brillouin laser oscillators offer powerful and flexible dynamics as the basis for mode-locked lasers, microwave oscillators, and optical gyroscopes in a variety of optical systems. However, Brillouin interactions are markedly weak in conventional silicon photonic waveguides, stifling progress toward silicon-based Brillouin lasers. The recent advent of hybrid photonic-phononic waveguides has revealed Brillouin interactions to be one of the strongest and most tailorable nonlinearities in silicon. In this study, we have harnessed these engineered nonlinearities to demonstrate Brillouin lasing in silicon. Moreover, we show that this silicon-based Brillouin laser enters a regime of dynamics in which optical self-oscillation produces phonon linewidth narrowing. Our results provide a platform to develop a range of applications for monolithic integration within silicon photonic circuits.}, } @article {pmid29880686, year = {2018}, author = {Pan, X and Ma, J and Su, X and Cao, P and Chang, W and Liu, Z and Zhang, X and Li, M}, title = {Structure of the maize photosystem I supercomplex with light-harvesting complexes I and II.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1109-1113}, doi = {10.1126/science.aat1156}, pmid = {29880686}, issn = {1095-9203}, mesh = {Chlorophyll/chemistry ; Cryoelectron Microscopy ; Light-Harvesting Protein Complexes/*chemistry/ultrastructure ; *Photosynthesis ; Photosystem I Protein Complex/*chemistry/ultrastructure ; Protein Conformation ; Zea mays/*enzymology ; }, abstract = {Plants regulate photosynthetic light harvesting to maintain balanced energy flux into photosystems I and II (PSI and PSII). Under light conditions favoring PSII excitation, the PSII antenna, light-harvesting complex II (LHCII), is phosphorylated and forms a supercomplex with PSI core and the PSI antenna, light-harvesting complex I (LHCI). Both LHCI and LHCII then transfer excitation energy to the PSI core. We report the structure of maize PSI-LHCI-LHCII solved by cryo-electron microscopy, revealing the recognition site between LHCII and PSI. The PSI subunits PsaN and PsaO are observed at the PSI-LHCI interface and the PSI-LHCII interface, respectively. Each subunit relays excitation to PSI core through a pair of chlorophyll molecules, thus revealing previously unseen paths for energy transfer between the antennas and the PSI core.}, } @article {pmid29880685, year = {2018}, author = {Tittl, A and Leitis, A and Liu, M and Yesilkoy, F and Choi, DY and Neshev, DN and Kivshar, YS and Altug, H}, title = {Imaging-based molecular barcoding with pixelated dielectric metasurfaces.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1105-1109}, doi = {10.1126/science.aas9768}, pmid = {29880685}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Metasurfaces provide opportunities for wavefront control, flat optics, and subwavelength light focusing. We developed an imaging-based nanophotonic method for detecting mid-infrared molecular fingerprints and implemented it for the chemical identification and compositional analysis of surface-bound analytes. Our technique features a two-dimensional pixelated dielectric metasurface with a range of ultrasharp resonances, each tuned to a discrete frequency; this enables molecular absorption signatures to be read out at multiple spectral points, and the resulting information is then translated into a barcode-like spatial absorption map for imaging. The signatures of biological, polymer, and pesticide molecules can be detected with high sensitivity, covering applications such as biosensing and environmental monitoring. Our chemically specific technique can resolve absorption fingerprints without the need for spectrometry, frequency scanning, or moving mechanical parts, thereby paving the way toward sensitive and versatile miniaturized mid-infrared spectroscopy devices.}, } @article {pmid29880684, year = {2018}, author = {Hassan, N and Cunningham, S and Mourigal, M and Zhilyaeva, EI and Torunova, SA and Lyubovskaya, RN and Schlueter, JA and Drichko, N}, title = {Evidence for a quantum dipole liquid state in an organic quasi-two-dimensional material.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1101-1104}, doi = {10.1126/science.aan6286}, pmid = {29880684}, issn = {1095-9203}, abstract = {Mott insulators are commonly pictured with electrons localized on lattice sites, with their low-energy degrees of freedom involving spins only. Here, we observe emergent charge degrees of freedom in a molecule-based Mott insulator κ-(BEDT-TTF)2Hg(SCN)2Br, resulting in a quantum dipole liquid state. Electrons localized on molecular dimer lattice sites form electric dipoles that do not order at low temperatures and fluctuate with frequency detected experimentally in our Raman spectroscopy experiments. The heat capacity and Raman scattering response are consistent with a scenario in which the composite spin and electric dipole degrees of freedom remain fluctuating down to the lowest measured temperatures.}, } @article {pmid29880683, year = {2018}, author = {Eigenbrode, JL and Summons, RE and Steele, A and Freissinet, C and Millan, M and Navarro-González, R and Sutter, B and McAdam, AC and Franz, HB and Glavin, DP and Archer, PD and Mahaffy, PR and Conrad, PG and Hurowitz, JA and Grotzinger, JP and Gupta, S and Ming, DW and Sumner, DY and Szopa, C and Malespin, C and Buch, A and Coll, P}, title = {Organic matter preserved in 3-billion-year-old mudstones at Gale crater, Mars.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1096-1101}, doi = {10.1126/science.aas9185}, pmid = {29880683}, issn = {1095-9203}, abstract = {Establishing the presence and state of organic matter, including its possible biosignatures, in martian materials has been an elusive quest, despite limited reports of the existence of organic matter on Mars. We report the in situ detection of organic matter preserved in lacustrine mudstones at the base of the ~3.5-billion-year-old Murray formation at Pahrump Hills, Gale crater, by the Sample Analysis at Mars instrument suite onboard the Curiosity rover. Diverse pyrolysis products, including thiophenic, aromatic, and aliphatic compounds released at high temperatures (500° to 820°C), were directly detected by evolved gas analysis. Thiophenes were also observed by gas chromatography-mass spectrometry. Their presence suggests that sulfurization aided organic matter preservation. At least 50 nanomoles of organic carbon persists, probably as macromolecules containing 5% carbon as organic sulfur molecules.}, } @article {pmid29880682, year = {2018}, author = {Webster, CR and Mahaffy, PR and Atreya, SK and Moores, JE and Flesch, GJ and Malespin, C and McKay, CP and Martinez, G and Smith, CL and Martin-Torres, J and Gomez-Elvira, J and Zorzano, MP and Wong, MH and Trainer, MG and Steele, A and Archer, D and Sutter, B and Coll, PJ and Freissinet, C and Meslin, PY and Gough, RV and House, CH and Pavlov, A and Eigenbrode, JL and Glavin, DP and Pearson, JC and Keymeulen, D and Christensen, LE and Schwenzer, SP and Navarro-Gonzalez, R and Pla-García, J and Rafkin, SCR and Vicente-Retortillo, Á and Kahanpää, H and Viudez-Moreiras, D and Smith, MD and Harri, AM and Genzer, M and Hassler, DM and Lemmon, M and Crisp, J and Sander, SP and Zurek, RW and Vasavada, AR}, title = {Background levels of methane in Mars' atmosphere show strong seasonal variations.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1093-1096}, doi = {10.1126/science.aaq0131}, pmid = {29880682}, issn = {1095-9203}, abstract = {Variable levels of methane in the martian atmosphere have eluded explanation partly because the measurements are not repeatable in time or location. We report in situ measurements at Gale crater made over a 5-year period by the Tunable Laser Spectrometer on the Curiosity rover. The background levels of methane have a mean value 0.41 ± 0.16 parts per billion by volume (ppbv) (95% confidence interval) and exhibit a strong, repeatable seasonal variation (0.24 to 0.65 ppbv). This variation is greater than that predicted from either ultraviolet degradation of impact-delivered organics on the surface or from the annual surface pressure cycle. The large seasonal variation in the background and occurrences of higher temporary spikes (~7 ppbv) are consistent with small localized sources of methane released from martian surface or subsurface reservoirs.}, } @article {pmid29880681, year = {2018}, author = {Zhang, YY and Fu, ZY and Wei, J and Qi, W and Baituola, G and Luo, J and Meng, YJ and Guo, SY and Yin, H and Jiang, SY and Li, YF and Miao, HH and Liu, Y and Wang, Y and Li, BL and Ma, YT and Song, BL}, title = {A LIMA1 variant promotes low plasma LDL cholesterol and decreases intestinal cholesterol absorption.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1087-1092}, doi = {10.1126/science.aao6575}, pmid = {29880681}, issn = {1095-9203}, mesh = {Animals ; Asian Continental Ancestry Group/*genetics ; China ; Cholesterol, LDL/blood/*metabolism ; Cytoskeletal Proteins/genetics/*metabolism ; *Frameshift Mutation ; Genetic Variation ; Hep G2 Cells ; Humans ; Intestinal Absorption/*genetics ; Intestinal Mucosa/*metabolism ; Kazakhstan/ethnology ; Membrane Proteins/metabolism ; Mice ; Mice, Knockout ; Myosin Heavy Chains/metabolism ; Myosin Type V/metabolism ; Pedigree ; Protein Binding ; Protein Transport ; }, abstract = {A high concentration of low-density lipoprotein cholesterol (LDL-C) is a major risk factor for cardiovascular disease. Although LDL-C levels vary among humans and are heritable, the genetic factors affecting LDL-C are not fully characterized. We identified a rare frameshift variant in the LIMA1 (also known as EPLIN or SREBP3) gene from a Chinese family of Kazakh ethnicity with inherited low LDL-C and reduced cholesterol absorption. In a mouse model, LIMA1 was mainly expressed in the small intestine and localized on the brush border membrane. LIMA1 bridged NPC1L1, an essential protein for cholesterol absorption, to a transportation complex containing myosin Vb and facilitated cholesterol uptake. Similar to the human phenotype, Lima1-deficient mice displayed reduced cholesterol absorption and were resistant to diet-induced hypercholesterolemia. Through our study of both mice and humans, we identify LIMA1 as a key protein regulating intestinal cholesterol absorption.}, } @article {pmid29880680, year = {2018}, author = {Bashir, S and Niazi, NK and Watto, MA}, title = {Injustices of foreign investment in coal.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1081}, doi = {10.1126/science.aat9852}, pmid = {29880680}, issn = {1095-9203}, } @article {pmid29880679, year = {2018}, author = {Ceballos, G and Ehrlich, PR}, title = {The misunderstood sixth mass extinction.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1080-1081}, doi = {10.1126/science.aau0191}, pmid = {29880679}, issn = {1095-9203}, mesh = {Animals ; *Conservation of Natural Resources ; *Extinction, Biological ; *Human Activities ; Humans ; }, } @article {pmid29880678, year = {2018}, author = {Sonne, C and Langebæk, R and Dietz, R and Andersen-Ranberg, E and Houser, G and Hansen, AJ and Sinding, MS and Olsen, MT and Egevang, C and Gilbert, MTP and Meldgaard, M}, title = {Greenland sled dogs at risk of extinction.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1080}, doi = {10.1126/science.aat9578}, pmid = {29880678}, issn = {1095-9203}, mesh = {Animals ; Breeding ; Climate Change ; Dog Diseases/epidemiology ; *Dogs ; *Endangered Species ; *Extinction, Biological ; Greenland ; Risk ; }, } @article {pmid29880677, year = {2018}, author = {Ram, N and Guerrini, CJ and McGuire, AL}, title = {Genealogy databases and the future of criminal investigation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1078-1079}, doi = {10.1126/science.aau1083}, pmid = {29880677}, issn = {1095-9203}, support = {K01 HG009355/HG/NHGRI NIH HHS/United States ; R01 HG008918/HG/NHGRI NIH HHS/United States ; }, mesh = {Criminal Law/*ethics ; Databases, Genetic/*ethics ; *Genealogy and Heraldry ; *Genetic Privacy ; Humans ; Law Enforcement/*ethics ; }, } @article {pmid29880675, year = {2018}, author = {Rossant, J and Tam, PPL}, title = {Exploring early human embryo development.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1075-1076}, doi = {10.1126/science.aas9302}, pmid = {29880675}, issn = {1095-9203}, mesh = {Blastocyst ; Cell Culture Techniques ; *Embryo, Mammalian ; *Embryonic Development/genetics ; Fertilization in Vitro ; Gene Expression Profiling ; Humans ; *Models, Biological ; Sequence Analysis, RNA ; Single-Cell Analysis ; Stem Cells ; }, } @article {pmid29880674, year = {2018}, author = {Powell, BJ}, title = {The expanding materials multiverse.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1073-1074}, doi = {10.1126/science.aat7282}, pmid = {29880674}, issn = {1095-9203}, } @article {pmid29880673, year = {2018}, author = {Pendergrass, AG}, title = {What precipitation is extreme?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1072-1073}, doi = {10.1126/science.aat1871}, pmid = {29880673}, issn = {1095-9203}, } @article {pmid29880672, year = {2018}, author = {Thomma, BPHJ and Cook, DE}, title = {Targeting microbial pathogens.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1070-1071}, doi = {10.1126/science.aat9343}, pmid = {29880672}, issn = {1095-9203}, } @article {pmid29880671, year = {2018}, author = {Nieder, A}, title = {Honey bees zero in on the empty set.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1069-1070}, doi = {10.1126/science.aat8958}, pmid = {29880671}, issn = {1095-9203}, mesh = {Animals ; Bees ; *Flowers ; *Seasons ; }, } @article {pmid29880670, year = {2018}, author = {Ten Kate, IL}, title = {Organic molecules on Mars.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1068-1069}, doi = {10.1126/science.aat2662}, pmid = {29880670}, issn = {1095-9203}, mesh = {Exobiology ; *Extraterrestrial Environment ; *Mars ; Organic Chemicals ; }, } @article {pmid29880669, year = {2018}, author = {Goldfarb, B}, title = {Beavers, rebooted.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1058-1061}, doi = {10.1126/science.360.6393.1058}, pmid = {29880669}, issn = {1095-9203}, mesh = {Animals ; Environmental Restoration and Remediation/*methods ; *Rodentia ; Wood ; }, } @article {pmid29880668, year = {2018}, author = {Clery, D}, title = {Middleweight black holes found at last.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1057}, doi = {10.1126/science.360.6393.1057}, pmid = {29880668}, issn = {1095-9203}, } @article {pmid29880667, year = {2018}, author = {Lawler, A}, title = {Dig seeks site of first English settlement in the New World.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1056}, doi = {10.1126/science.360.6393.1056}, pmid = {29880667}, issn = {1095-9203}, } @article {pmid29880666, year = {2018}, author = {Kaiser, J}, title = {No bias found in NIH reviews.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1055}, doi = {10.1126/science.360.6393.1055}, pmid = {29880666}, issn = {1095-9203}, mesh = {Humans ; *National Institutes of Health (U.S.) ; *Peer Review, Research ; Racism ; Sexism ; United States ; }, } @article {pmid29880665, year = {2018}, author = {Voosen, P}, title = {NASA Curiosity rover hits organic pay dirt on Mars.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1054-1055}, doi = {10.1126/science.360.6393.1054}, pmid = {29880665}, issn = {1095-9203}, } @article {pmid29880664, year = {2018}, author = {Normile, D}, title = {China takes new steps to lure science talent from abroad.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1053-1054}, doi = {10.1126/science.360.6393.1053}, pmid = {29880664}, issn = {1095-9203}, } @article {pmid29880663, year = {2018}, author = {Wade, L}, title = {She studied Mexico City. Can she lead it, too?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1052-1053}, doi = {10.1126/science.360.6393.1052}, pmid = {29880663}, issn = {1095-9203}, } @article {pmid29880662, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1050-1051}, doi = {10.1126/science.360.6393.1050}, pmid = {29880662}, issn = {1095-9203}, } @article {pmid29880661, year = {2018}, author = {Frieden, TR}, title = {Still not ready for Ebola.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1049}, doi = {10.1126/science.aau3345}, pmid = {29880661}, issn = {1095-9203}, mesh = {Democratic Republic of the Congo/epidemiology ; Disease Outbreaks/*prevention & control ; *Ebola Vaccines ; Ebolavirus/*isolation & purification ; Hemorrhagic Fever, Ebola/*epidemiology/*prevention & control ; Humans ; World Health Organization ; }, } @article {pmid29880660, year = {2018}, author = {Kronenberg, ZN and Fiddes, IT and Gordon, D and Murali, S and Cantsilieris, S and Meyerson, OS and Underwood, JG and Nelson, BJ and Chaisson, MJP and Dougherty, ML and Munson, KM and Hastie, AR and Diekhans, M and Hormozdiari, F and Lorusso, N and Hoekzema, K and Qiu, R and Clark, K and Raja, A and Welch, AE and Sorensen, M and Baker, C and Fulton, RS and Armstrong, J and Graves-Lindsay, TA and Denli, AM and Hoppe, ER and Hsieh, P and Hill, CM and Pang, AWC and Lee, J and Lam, ET and Dutcher, SK and Gage, FH and Warren, WC and Shendure, J and Haussler, D and Schneider, VA and Cao, H and Ventura, M and Wilson, RK and Paten, B and Pollen, A and Eichler, EE}, title = {High-resolution comparative analysis of great ape genomes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {}, pmid = {29880660}, issn = {1095-9203}, support = {U41 HG007635/HG/NHGRI NIH HHS/United States ; R01 HG008742/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; F30 HG009478/HG/NHGRI NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; U24 HG009081/HG/NHGRI NIH HHS/United States ; R01 HG006283/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; U54 HG007990/HG/NHGRI NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Contig Mapping ; *Evolution, Molecular ; Genetic Variation ; *Genome, Human ; Hominidae/*genetics ; Humans ; Molecular Sequence Annotation ; Sequence Analysis, DNA ; }, abstract = {Genetic studies of human evolution require high-quality contiguous ape genome assemblies that are not guided by the human reference. We coupled long-read sequence assembly and full-length complementary DNA sequencing with a multiplatform scaffolding approach to produce ab initio chimpanzee and orangutan genome assemblies. By comparing these with two long-read de novo human genome assemblies and a gorilla genome assembly, we characterized lineage-specific and shared great ape genetic variation ranging from single- to mega-base pair-sized variants. We identified ~17,000 fixed human-specific structural variants identifying genic and putative regulatory changes that have emerged in humans since divergence from nonhuman apes. Interestingly, these variants are enriched near genes that are down-regulated in human compared to chimpanzee cerebral organoids, particularly in cells analogous to radial glial neural progenitors.}, } @article {pmid29880425, year = {2018}, author = {Jarillo, S and Fridlund, A and Crivelli, C and Fernández-Dols, JM and Russell, JA}, title = {Rejoinder to Kret and Straffon.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {198-200}, doi = {10.1016/j.jhevol.2018.03.002}, pmid = {29880425}, issn = {1095-8606}, } @article {pmid29880230, year = {2018}, author = {}, title = {Christine Petersen: Pioneering Leishmania Research in Man…and Man's Best Friend.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {543-544}, doi = {10.1016/j.pt.2018.05.002}, pmid = {29880230}, issn = {1471-5007}, mesh = {Animals ; Humans ; *Leishmania ; Parasitology/*trends ; Research/*trends ; }, } @article {pmid29880062, year = {2018}, author = {Wang, J and Kurilshikov, A and Radjabzadeh, D and Turpin, W and Croitoru, K and Bonder, MJ and Jackson, MA and Medina-Gomez, C and Frost, F and Homuth, G and Rühlemann, M and Hughes, D and Kim, HN and , and Spector, TD and Bell, JT and Steves, CJ and Timpson, N and Franke, A and Wijmenga, C and Meyer, K and Kacprowski, T and Franke, L and Paterson, AD and Raes, J and Kraaij, R and Zhernakova, A}, title = {Meta-analysis of human genome-microbiome association studies: the MiBioGen consortium initiative.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {101}, pmid = {29880062}, issn = {2049-2618}, support = {MC_UU_12013/1-9//Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; K01 HL127159/HL/NHLBI NIH HHS/United States ; 202802/Z/16/Z//Wellcome Trust/United Kingdom ; CMF108031//CIHR/Canada ; DP2 OD007444/OD/NIH HHS/United States ; GET-101831//CIHR/Canada ; MC_UU_12013/3//Medical Research Council/United Kingdom ; }, mesh = {Bacteria/*classification/genetics/*isolation & purification ; Cohort Studies ; Gastrointestinal Microbiome/*genetics ; Genetic Variation/genetics ; Genome, Human/*genetics ; Genome-Wide Association Study ; Humans ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: In recent years, human microbiota, especially gut microbiota, have emerged as an important yet complex trait influencing human metabolism, immunology, and diseases. Many studies are investigating the forces underlying the observed variation, including the human genetic variants that shape human microbiota. Several preliminary genome-wide association studies (GWAS) have been completed, but more are necessary to achieve a fuller picture.

RESULTS: Here, we announce the MiBioGen consortium initiative, which has assembled 18 population-level cohorts and some 19,000 participants. Its aim is to generate new knowledge for the rapidly developing field of microbiota research. Each cohort has surveyed the gut microbiome via 16S rRNA sequencing and genotyped their participants with full-genome SNP arrays. We have standardized the analytical pipelines for both the microbiota phenotypes and genotypes, and all the data have been processed using identical approaches. Our analysis of microbiome composition shows that we can reduce the potential artifacts introduced by technical differences in generating microbiota data. We are now in the process of benchmarking the association tests and performing meta-analyses of genome-wide associations. All pipeline and summary statistics results will be shared using public data repositories.

CONCLUSION: We present the largest consortium to date devoted to microbiota-GWAS. We have adapted our analytical pipelines to suit multi-cohort analyses and expect to gain insight into host-microbiota cross-talk at the genome-wide level. And, as an open consortium, we invite more cohorts to join us (by contacting one of the corresponding authors) and to follow the analytical pipeline we have developed.}, } @article {pmid29880044, year = {2018}, author = {Katusabe, JL and Hodges, A and Galiwango, GW and Mulogo, EM}, title = {Challenges to achieving low palatal fistula rates following primary cleft palate repair: experience of an institution in Uganda.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {358}, pmid = {29880044}, issn = {1756-0500}, mesh = {Adolescent ; Child ; Child, Preschool ; Cleft Palate/*surgery ; Female ; Fistula/*epidemiology/etiology ; Humans ; Infant ; Male ; Malnutrition/complications/*epidemiology ; Oral Surgical Procedures/adverse effects/*statistics & numerical data ; *Outcome and Process Assessment (Health Care) ; Palate/*pathology/surgery ; Postoperative Complications/*epidemiology/etiology ; Prospective Studies ; Uganda ; }, abstract = {OBJECTIVE: To determine frequency of palatal fistula following primary cleft palate repair and the associated factors as a measure of cleft palate repair outcome and its challenges at a cleft centre in Uganda.

RESULTS: Between May and December 2016, 54 children with cleft palate were followed up at Comprehensive Rehabilitation services of Uganda (CoRSU) hospital, from time of primary cleft palate repair until at least 3 months postoperative to determine whether they developed palatal fistula or not. Frequency of palatal fistula was 35%. Factors associated with increased fistula formation were cleft width wider than 12 mm (p = 0.006), palatal index greater than 0.4 (p = 0.046), presence of malnutrition at initial outpatient assessment (p = 0.0057) and at time of surgery (p = 0.008), two-stage palate repair (p = 0.005) and postoperative infection (p = 0.003). Severe clefting (palatal index greater than 0.4) was seen in 74% of patients and malnutrition (Low weight for age) seen in 48% of patients. Palatal fistula rates at our institution were high compared to reports in literature. The high proportions of severe clefting and malnutrition observed in our population that was also poor and unable to afford feeding supplements increased likelihood of fistula formation and posed challenges to achieving low fistula rates in our setting.}, } @article {pmid29880041, year = {2018}, author = {Keri, KC and Regner, KR and Dall, AT and Park, F}, title = {Urinary exosomal expression of activator of G protein signaling 3 in polycystic kidney disease.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {359}, pmid = {29880041}, issn = {1756-0500}, support = {P50 DK079306/DK/NIDDK NIH HHS/United States ; P50DK079306//National Institutes of Health/ ; }, mesh = {Adult ; Aged ; Animals ; Biomarkers/urine ; Carrier Proteins/*urine ; Disease Models, Animal ; Exosomes/*metabolism ; Female ; Guanine Nucleotide Dissociation Inhibitors/*urine ; Humans ; Male ; Middle Aged ; Polycystic Kidney Diseases/*diagnosis/*urine ; Rats ; Rats, Sprague-Dawley ; Young Adult ; }, abstract = {OBJECTIVE: PKD is a genetic disease that is characterized by abnormally proliferative epithelial cells in the kidney and liver. Urinary exosomes have been previously examined as a source of unique proteins that may be used to diagnose and monitor the progression of PKD. Previous studies by our group have shown that AGS3, which is a receptor-independent regulator G-proteins, was markedly upregulated in RTECs during kidney injury including PKD. In this study, our goal was to determine whether AGS3 could be measured in exosomes using animals and humans with PKD.

RESULTS: In our study, urinary exosomes were isolated from PCK rats and the control Sprague-Dawley (SD) rats. AGS3 expression was significantly increased (P < 0.05) in PKD versus SD rats at 16 weeks of age. This increase was detectable in a time-dependent manner from 8 weeks of age and peaked at ~ 16-20 weeks (length of study). Similarly, in exosomes from human urine samples with PKD, AGS3 expression was significantly increased (P < 0.05) compared to healthy human controls where AGS3 was largely undetectable. In conclusion, the detection of AGS3 in urinary exosomes may be a novel biomarker for PKD, and provide new insight into the biology of tubular epithelial cell function during cystic disease progression.}, } @article {pmid29880035, year = {2018}, author = {Anglès d'Auriac, MB and Sirevåg, R}, title = {Multiplex PCR for the simultaneous detection of the Enterobacterial gene wecA, the Shiga Toxin genes (stx1 and stx2) and the Intimin gene (eae).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {360}, pmid = {29880035}, issn = {1756-0500}, mesh = {Adhesins, Bacterial/*genetics ; Antigens, Bacterial/*genetics ; Diarrhea/*diagnosis ; Enterobacteriaceae/*genetics ; Escherichia coli Proteins/*genetics ; Humans ; Multiplex Polymerase Chain Reaction/*methods ; Sequence Analysis/*methods ; Shiga Toxin 1/*genetics ; Shiga Toxin 2/*genetics ; Transferases (Other Substituted Phosphate Groups)/*genetics ; }, abstract = {OBJECTIVES: The aetiology of several human diarrhoeas has been increasingly associated with the presence of virulence factors rather than with the bacterial species hosting the virulence genes, exemplified by the sporadic emergence of new bacterial hosts. Two important virulence factors are the Shiga toxin (Stx) and the E. coli outer membrane protein (Eae) or intimin, encoded by the stx and eae genes, respectively. Although several polymerase chain reaction (PCR) protocols target these virulence genes, few aim at detecting all variants or have an internal amplification control (IAC) included in a multiplex assay. The objective of this work was to develop a simple multiplex PCR assay in order to detect all stx and eae variants, as well as to detect bacteria belonging to the Enterobacteriaceae, also used as an IAC.

RESULTS: The wecA gene coding for the production of the Enterobacterial Common Antigen was used to develop an Enterobacteriaceae specific qPCR. Universal primers for the detection of stx and eae were developed and linked to a wecA primer pair in a robust triplex PCR. In addition, subtyping of the stx genes was achieved by subjecting the PCR products to restriction digestion and semi-nested duplex PCR, providing a simple screening assay for human diarrhoea diagnostic.}, } @article {pmid29880030, year = {2018}, author = {Sigar, IM and Schripsema, JH and Kelly, KA and Murthy, AK and Manam, S and Ramsey, KH}, title = {Elimination of Mycoplasma contamination in Chlamydia stocks as a result of in vivo passage or plaque isolation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {361}, pmid = {29880030}, issn = {1756-0500}, mesh = {Animals ; *Chlamydia ; Female ; *Genetic Techniques ; HeLa Cells ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Microbiological Techniques/*methods ; *Mycoplasma ; Polymerase Chain Reaction ; }, abstract = {OBJECTIVE: This study aims to eliminate Mycoplasma spp. contamination from laboratory stocks of Chlamydia spp. by in vivo passage or by plaque assay.

RESULTS: We have described two methods of eliminating Mycoplasma contamination from Chlamydia laboratory stocks. We conclude that Mycoplasma species commonly contaminating chlamydial stocks do not survive passage in mice. Chlamydia may also be derived Mycoplasma-free by plaque assay.}, } @article {pmid29879983, year = {2018}, author = {Ross, BC and Boguslav, M and Weeks, H and Costello, JC}, title = {Simulating heterogeneous populations using Boolean models.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {64}, pmid = {29879983}, issn = {1752-0509}, support = {P30 CA046934/CA/NCI NIH HHS/United States ; T15 LM009451/LM/NLM NIH HHS/United States ; LM009451//U.S. National Library of Medicine/ ; }, abstract = {BACKGROUND: Certain biological processes, such as the development of cancer and immune activation, can be controlled by rare cellular events that are difficult to capture computationally through simulations of individual cells. Information about such rare events can be gleaned from an attractor analysis, for which a variety of methods exist (in particular for Boolean models). However, explicitly simulating a defined mixed population of cells in a way that tracks even the rarest subpopulations remains an open challenge.

RESULTS: Here we show that when cellular states are described using a Boolean network model, one can exactly simulate the dynamics of non-interacting, highly heterogeneous populations directly, without having to model the various subpopulations. This strategy captures even the rarest outcomes of the model with no sampling error. Our method can incorporate heterogeneity in both cell state and, by augmenting the model, the underlying rules of the network as well (e.g., introducing loss-of-function genetic alterations). We demonstrate our method by using it to simulate a heterogeneous population of Boolean networks modeling the T-cell receptor, spanning ∼ 1020 distinct cellular states and mutational profiles.

CONCLUSIONS: We have developed a method for using Boolean models to perform a population-level simulation, in which the population consists of non-interacting individuals existing in different states. This approach can be used even when there are far too many distinct subpopulations to model individually.}, } @article {pmid29879919, year = {2018}, author = {Huang, J and Zheng, J and Yuan, H and McGinnis, K}, title = {Distinct tissue-specific transcriptional regulation revealed by gene regulatory networks in maize.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {111}, pmid = {29879919}, issn = {1471-2229}, support = {035919//Directorate for Biological Sciences/ ; }, mesh = {*Gene Expression Regulation, Plant/genetics/physiology ; Gene Regulatory Networks/*genetics/physiology ; Genes, Plant/genetics/physiology ; Meristem/metabolism ; Plant Leaves/metabolism ; Plant Roots/metabolism ; Plant Shoots/metabolism ; Seeds/metabolism ; Transcription Factors/*genetics/physiology ; Zea mays/*genetics/metabolism ; }, abstract = {BACKGROUND: Transcription factors (TFs) are proteins that can bind to DNA sequences and regulate gene expression. Many TFs are master regulators in cells that contribute to tissue-specific and cell-type-specific gene expression patterns in eukaryotes. Maize has been a model organism for over one hundred years, but little is known about its tissue-specific gene regulation through TFs. In this study, we used a network approach to elucidate gene regulatory networks (GRNs) in four tissues (leaf, root, SAM and seed) in maize. We utilized GENIE3, a machine-learning algorithm combined with large quantity of RNA-Seq expression data to construct four tissue-specific GRNs. Unlike some other techniques, this approach is not limited by high-quality Position Weighed Matrix (PWM), and can therefore predict GRNs for over 2000 TFs in maize.

RESULTS: Although many TFs were expressed across multiple tissues, a multi-tiered analysis predicted tissue-specific regulatory functions for many transcription factors. Some well-studied TFs emerged within the four tissue-specific GRNs, and the GRN predictions matched expectations based upon published results for many of these examples. Our GRNs were also validated by ChIP-Seq datasets (KN1, FEA4 and O2). Key TFs were identified for each tissue and matched expectations for key regulators in each tissue, including GO enrichment and identity with known regulatory factors for that tissue. We also found functional modules in each network by clustering analysis with the MCL algorithm.

CONCLUSIONS: By combining publicly available genome-wide expression data and network analysis, we can uncover GRNs at tissue-level resolution in maize. Since ChIP-Seq and PWMs are still limited in several model organisms, our study provides a uniform platform that can be adapted to any species with genome-wide expression data to construct GRNs. We also present a publicly available database, maize tissue-specific GRN (mGRN, https://www.bio.fsu.edu/mcginnislab/mgrn/), for easy querying. All source code and data are available at Github (https://github.com/timedreamer/maize_tissue-specific_GRN).}, } @article {pmid29879918, year = {2018}, author = {Taudt, A and Roquis, D and Vidalis, A and Wardenaar, R and Johannes, F and Colome-Tatché-Tatché, M}, title = {METHimpute: imputation-guided construction of complete methylomes from WGBS data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {444}, pmid = {29879918}, issn = {1471-2164}, support = {291763//Seventh Framework Programme/ ; VH-NG-1219//Helmholtz Association's Initiative and Networking Fund/ ; }, mesh = {*DNA Methylation/drug effects ; *Genomics ; Markov Chains ; Plants/genetics ; Sequence Analysis, DNA ; Sulfites/pharmacology ; *Whole Genome Sequencing ; }, abstract = {BACKGROUND: Whole-genome bisulfite sequencing (WGBS) has become the standard method for interrogating plant methylomes at base resolution. However, deep WGBS measurements remain cost prohibitive for large, complex genomes and for population-level studies. As a result, most published plant methylomes are sequenced far below saturation, with a large proportion of cytosines having either missing data or insufficient coverage.

RESULTS: Here we present METHimpute, a Hidden Markov Model (HMM) based imputation algorithm for the analysis of WGBS data. Unlike existing methods, METHimpute enables the construction of complete methylomes by inferring the methylation status and level of all cytosines in the genome regardless of coverage. Application of METHimpute to maize, rice and Arabidopsis shows that the algorithm infers cytosine-resolution methylomes with high accuracy from data as low as 6X, compared to data with 60X, thus making it a cost-effective solution for large-scale studies.

CONCLUSIONS: METHimpute provides methylation status calls and levels for all cytosines in the genome regardless of coverage, thus yielding complete methylomes even with low-coverage WGBS datasets. The method has been extensively tested in plants, but should also be applicable to other species. An implementation is available on Bioconductor.}, } @article {pmid29879910, year = {2018}, author = {Chen, JY and Zhang, HW and Zhang, HL and Ying, JZ and Ma, LY and Zhuang, JY}, title = {Natural variation at qHd1 affects heading date acceleration at high temperatures with pleiotropism for yield traits in rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {112}, pmid = {29879910}, issn = {1471-2229}, support = {31701398//National Natural Science Foundation of China/ ; 31371605//National Natural Science Foundation of China/ ; 2014AA10A604-15//Chinese 863 Program/ ; }, mesh = {Edible Grain/*growth & development ; Genes, Plant/genetics/physiology ; Genetic Pleiotropy/*genetics/physiology ; Genetic Variation/genetics/physiology ; Heat-Shock Response ; Hot Temperature ; Oryza/*genetics/growth & development ; Photoperiod ; Plant Breeding ; Quantitative Trait Loci/genetics/physiology ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Rice is highly sensitive to temperature fluctuations. Recently, the frequent occurrence of high temperature stress has heavily influenced rice production. Proper heading date in specific environmental conditions could ensure high grain yield. Rice heading greatly depends on the accurate measurement of environmental changes, particularly in day length and temperature. In contrary to the detailed understanding of the photoperiod pathway, little has been known about how temperature regulates the genetic control of rice heading.

RESULTS: Near isogenic lines that were segregated for qHd1, were developed from a cross between indica rice varieties Zhenshan 97 (ZS97) and Milyang 46 (MY46). Using a five sowing-date experiment in the paddy field, we observed the involvement of qHd1 in temperature responses. With the gradual increase of temperature from Trial I to V, heading date of MY46 homozygotes continued to decrease for about 5 d per trial from 76 to 58 d, while that of ZS97 homozygotes was promoted at the same rate from Trial I to III and then stabilized at 69 d. This thermal response was confirmed in a temperature-gradient experiment conducted in the phytotron. It is also found that tolerance of the ZS97 allele to heading acceleration at high temperature was associated with higher grain weight that resulted in higher grain yield. Then, by qRT-PCR and RNA-seq, we found the pathway OsMADS51-Ehd1-RFT1/Hd3a underlying the qHd1-mediated floral response to temperature. By sequence comparison, OsMADS51 for qHd1 displayed a 9.5-kb insertion in the 1st intron of the ZS97 allele compared to the MY46 allele. Furthermore, this large insertion is commonly found in major early-season indica rice varieties, but not in the middle- and late-season ones, which corresponds to the requirement for high-temperature tolerance during the heading and grain-filling stages of early-season rice.

CONCLUSIONS: Beneficial alleles at qHd1 confer tolerance to high temperatures at the heading and grain-filling stages, playing a significant role in the eco-geographical adaptation of early-season indica rice during modern breeding. These results, together with the underlying OsMADS51-Ehd1-RFT1/Hd3a floral pathway, provide valuable information for better understanding the molecular mechanism of temperature responsive regulation of heading date and yield traits in rice.}, } @article {pmid29879907, year = {2018}, author = {Lima, JF and Carvalho, J and Pinto-Ribeiro, I and Almeida, C and Wengel, J and Cerqueira, L and Figueiredo, C and Oliveira, C and Azevedo, NF}, title = {Targeting miR-9 in gastric cancer cells using locked nucleic acid oligonucleotides.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {6}, pmid = {29879907}, issn = {1471-2199}, support = {SFRH/BDE/51909/2012//Fundação para a Ciência e a Tecnologia/International ; SFRH/BD/110803/2015//Fundação para a Ciência e a Tecnologia/International ; }, mesh = {Antigens, CD ; Cadherins/*genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Down-Regulation ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; MicroRNAs/*antagonists & inhibitors ; Oligonucleotides/*pharmacology ; Stomach Neoplasms/drug therapy/*genetics/metabolism ; }, abstract = {BACKGROUND: Gastric cancer is the third leading cause of cancer-related mortality worldwide. Recently, it has been demonstrated that gastric cancer cells display a specific miRNA expression profile, with increasing evidence of the role of miRNA-9 in this disease. miRNA-9 upregulation has been shown to influence the expression of E-cadherin-encoding gene, triggering cell motility and invasiveness.

RESULTS: In this study, we designed LNA anti-miRNA oligonucleotides with a complementary sequence to miRNA-9 and tested their properties to both detect and silence the target miRNA. We could identify and visualize the in vitro uptake of low-dosing LNA-based anti-miRNA oligonucleotides without any carrier or transfection agent, as early as 2 h after the addition of the oligonucleotide sequence to the culture medium. Furthermore, we were able to assess the silencing potential of miRNA-9, using different LNA anti-miRNA oligonucleotide designs, and to observe its subsequent effect on E-cadherin expression.

CONCLUSIONS: The administration of anti-miRNA sequences even at low-doses, rapidly repressed the target miRNA, and influenced the expression of E-cadherin by significantly increasing its levels.}, } @article {pmid29879905, year = {2018}, author = {Nakano, H and Miyazawa, H and Maeno, A and Shiroishi, T and Kakui, K and Koyanagi, R and Kanda, M and Satoh, N and Omori, A and Kohtsuka, H}, title = {Correction to: A new species of Xenoturbella from the western Pacific Ocean and the evolution of Xenoturbella.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {83}, pmid = {29879905}, issn = {1471-2148}, abstract = {After publication of Nakano et al. (2017) [1], the authors became aware of the fact that the new species-group name erected for the two specimens of a Japanese xenoturbellid species in the article is not available because Nakano et al. (2017) [1] does not meet the requirement of the amendment of Article 8.5.3 of the International Code of Zoological Nomenclature (the Code) [2]. The authors therefore describe the two xenoturbellids as a new species again in this correction article. Methods for morphological observation, DNA extraction and sequencing were as described in Nakano et al. (2017) [1]. The holotype and paratype specimens are deposited in the National Museum of Nature and Science, Tsukuba (NSMT), Japan. The DNA sequences obtained were deposited in the International Nucleotide Sequence Database (INSD).}, } @article {pmid29879904, year = {2018}, author = {Hou, L and Xu, M and Zhang, T and Xu, Z and Wang, W and Zhang, J and Yu, M and Ji, W and Zhu, C and Gong, Z and Gu, M and Jiang, J and Yu, H}, title = {Chromosome painting and its applications in cultivated and wild rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {110}, pmid = {29879904}, issn = {1471-2229}, support = {2016YFD0102001-006//The National Key Research and Development Program/ ; 31670313//The National Natural Science Foundation of China/ ; 15KJA180010//Key Project of Jiangsu Education Department of China/ ; YZ2017059//Yangzhou City Science and Technology Plan/ ; }, mesh = {Aneuploidy ; Chromosome Aberrations ; Chromosome Painting/*methods ; Chromosomes, Plant/*genetics/ultrastructure ; Genome, Plant/genetics ; In Situ Hybridization, Fluorescence ; Oligonucleotide Probes/genetics ; Oryza/*genetics ; Translocation, Genetic/genetics ; }, abstract = {BACKGROUND: The chromosome-specific probe is a fundamental tool of chromosome painting and has been commonly applied in mammalian species. The technology, however, has not been widely applied in plants due to a lack of methodologies for probe development. Identification and labeling of a large number of oligonucleotides (oligos) specific to a single chromosome offers us an opportunity to establish chromosome-specific probes in plants. However, never before has whole chromosome painting been performed in rice.

RESULTS: We developed a pooled chromosome 9-specific probe in rice, which contains 25,000 oligos based on the genome sequence of a japonica rice (Oryza sativa L., AA, 2n = 2× = 24). Chromosome 9 was easily identified in both japonica and indica rice using this chromosome 9-painting probe. The probe was also successfully used to identify and characterize chromosome 9 in additional lines of O. sativa, a translocation line, two new aneuploids associated with chromosome 9 and a wild rice (Oryza eichingeri A. Peter, CC, 2n = 2× = 24).

CONCLUSION: The study reveals that a pool of oligos specific to a chromosome is a useful tool for chromosome painting in rice.}, } @article {pmid29879903, year = {2018}, author = {de la Rosa Rodriguez, MA and Sugahara, G and Hooiveld, GJEJ and Ishida, Y and Tateno, C and Kersten, S}, title = {The whole transcriptome effects of the PPARα agonist fenofibrate on livers of hepatocyte humanized mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {443}, pmid = {29879903}, issn = {1471-2164}, support = {2014/12392/ALW//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/ ; CVON2014-ENERGISE//Netherlands Cardiovascular Research Initiative/Dutch Heart Foundation/ ; }, mesh = {Animals ; *Chimera ; Fenofibrate/*pharmacology ; Hepatocytes/*drug effects/*metabolism ; Humans ; Liver/*cytology ; Mice ; PPAR alpha/*agonists ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: The role of PPARα in gene regulation in mouse liver is well characterized. However, less is known about the role of PPARα in human liver. The aim of the present study was to better characterize the impact of PPARα activation on gene regulation in human liver. To that end, chimeric mice containing hepatocyte humanized livers were given an oral dose of 300 mg/kg fenofibrate daily for 4 days. Livers were collected and analyzed by hematoxilin and eosin staining, qPCR, and transcriptomics. Transcriptomics data were compared with existing datasets on PPARα activation in normal mouse liver, human primary hepatocytes, and human precision cut liver slices.

RESULTS: Of the different human liver models, the gene expression profile of hepatocyte humanized livers most closely resembled actual human liver. In the hepatocyte humanized mouse livers, the human hepatocytes exhibited excessive lipid accumulation. Fenofibrate increased the size of the mouse but not human hepatocytes, and tended to reduce steatosis in the human hepatocytes. Quantitative PCR indicated that induction of PPARα targets by fenofibrate was less pronounced in the human hepatocytes than in the residual mouse hepatocytes. Transcriptomics analysis indicated that, after filtering, a total of 282 genes was significantly different between fenofibrate- and control-treated mice (P < 0.01). 123 genes were significantly lower and 159 genes significantly higher in the fenofibrate-treated mice, including many established PPARα targets such as FABP1, HADHB, HADHA, VNN1, PLIN2, ACADVL and HMGCS2. According to gene set enrichment analysis, fenofibrate upregulated interferon/cytokine signaling-related pathways in hepatocyte humanized liver, but downregulated these pathways in normal mouse liver. Also, fenofibrate downregulated pathways related to DNA synthesis in hepatocyte humanized liver but not in normal mouse liver.

CONCLUSION: The results support the major role of PPARα in regulating hepatic lipid metabolism, and underscore the more modest effect of PPARα activation on gene regulation in human liver compared to mouse liver. The data suggest that PPARα may have a suppressive effect on DNA synthesis in human liver, and a stimulatory effect on interferon/cytokine signalling.}, } @article {pmid29879901, year = {2018}, author = {Gasperotti, AF and Revuelta, MV and Studdert, CA and Herrera Seitz, MK}, title = {Correction to: Identification of two different chemosensory pathways in representatives of the genus Halomonas.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {442}, pmid = {29879901}, issn = {1471-2164}, support = {NRF-CRP7-2010-02//National Research Foundation Singapore/International ; }, abstract = {Following the publication of this article [1], the authors noticed that Fig. 3 was missing. In that figure, one of the numbers corresponding to the Halomonas chemoreceptors was missing: namely, chemoreceptor 07070. The correct version of Fig. 3 has been included in this Correction.}, } @article {pmid29879900, year = {2018}, author = {Yang, C and Yang, Z and Zhao, L and Sun, F and Liu, B}, title = {A newly formed hexaploid wheat exhibits immediate higher tolerance to nitrogen-deficiency than its parental lines.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {113}, pmid = {29879900}, issn = {1471-2229}, support = {31670218//National Natural Science Foundation of China/ ; 31290211//National Natural Science Foundation of China/ ; 31300192//National Natural Science Foundation of China/ ; 11471069//National Natural Science Foundation of China/ ; 20160520062JH//Youth Science Foundation of Technology Development plan of Jilin Provincial Government/ ; }, mesh = {Adaptation, Physiological/genetics ; Diploidy ; Gene Expression Regulation, Plant ; Genes, Plant/genetics/physiology ; Nitrogen/*deficiency/metabolism ; Photosynthesis ; *Polyploidy ; Triticum/*genetics/metabolism/physiology ; }, abstract = {BACKGROUND: It is known that hexaploid common wheat (Triticum aestivum L.) has stronger adaptability to many stressful environments than its tetraploid wheat progenitor. However, the physiological basis and evolutionary course to acquire these enhanced adaptabilities by common wheat remain understudied. Here, we aimed to investigate whether and by what means tolerance to low-nitrogen manifested by common wheat may emerge immediately following allohexaploidization.

RESULTS: We compared traits related to nitrogen (N) metabolism in a synthetic allohexaploid wheat (neo-6×, BBAADD) mimicking natural common wheat, together with its tetraploid (BBAA, 4×) and diploid (DD, 2×) parents. We found that, under low nitrogen condition, neo-6× maintained largely normal photosynthesis, higher shoot N accumulation, and better N assimilation than its 4× and 2× parents. We showed that multiple mechanisms underlie the enhanced tolerance to N-deficiency in neo-6×. At morphological level, neo-6× has higher root/shoot ratio of biomass than its parents, which might be an adaptive growth strategy as more roots feed less shoots with N, thereby enabling higher N accumulation in the shoots. At electrophysiological level, H+ efflux in neo-6× is higher than in its 4× parent. A stronger H+ efflux may enable a higher N uptake capacity of neo-6×. At gene expression level, neo-6× displayed markedly higher expression levels of critical genes involved in N uptake than both of its 4× and 2× parents.

CONCLUSIONS: This study documents that allohexaploid wheat can attain immediate higher tolerance to N-deficiency compared with both of its 4× and 2× parents, and which was accomplished via multiple mechanisms.}, } @article {pmid29879899, year = {2018}, author = {van Unen, J and Botman, D and Yin, T and Wu, YI and Hink, MA and Gadella, TWJ and Postma, M and Goedhart, J}, title = {The C-terminus of the oncoprotein TGAT is necessary for plasma membrane association and efficient RhoA-mediated signaling.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {6}, pmid = {29879899}, issn = {1471-2121}, support = {VIDI//NWO-ALW/International ; Middelgroot//NWO/International ; }, mesh = {Actins/metabolism ; Amino Acid Sequence ; Cell Membrane/*metabolism ; HeLa Cells ; Humans ; Mitochondria/metabolism ; Mutation/genetics ; Oncogene Proteins/*chemistry/*metabolism ; Polymerization ; Protein Transport ; Rho Guanine Nucleotide Exchange Factors/*chemistry/*metabolism ; *Signal Transduction ; Structure-Activity Relationship ; Subcellular Fractions/metabolism ; Transcription Factors/metabolism ; rhoA GTP-Binding Protein/*metabolism ; }, abstract = {BACKGROUND: Rho guanine exchange factors (RhoGEFs) control cellular processes such as migration, adhesion and proliferation. Alternative splicing of the RhoGEF Trio produces TGAT. The RhoGEF TGAT is an oncoprotein with constitutive RhoGEF activity. We investigated whether the subcellular location of TGAT is critical for its RhoGEF activity.

METHODS: Since plasma membrane associated RhoGEFs are particularly effective at activating RhoA, plasma membrane localization of TGAT was examined. To this end, we developed a highly sensitive image analysis method to quantitatively measure plasma membrane association. The method requires a cytoplasmic marker and a plasma membrane marker, which are co-imaged with the tagged protein of interest. Linear unmixing is performed to determine the plasma membrane and cytoplasmic component in the fluorescence signal of protein of interest.

RESULTS: The analysis revealed that wild-type TGAT is partially co-localized with the plasma membrane. Strikingly, cysteine TGAT-mutants lacking one or more putative palmitoylation sites in the C-tail, still showed membrane association. In contrast, a truncated variant, lacking the last 15 amino acids, TGATΔ15, lost membrane association. We show that membrane localization of TGAT was responsible for high RhoGEF activity by using a RhoA FRET-sensor and by determining F-actin levels. Mutants of TGAT that still maintained membrane association showed similar activity as wild-type TGAT. In contrast, the activity was abrogated for the cytoplasmic TGATΔ15 variant. Synthetic recruitment of TGATΔ15 to membranes confirmed that TGAT effectively activates RhoA at the plasma membrane.

CONCLUSION: Together, these results show that membrane association of TGAT is critical for its activity.}, } @article {pmid29879898, year = {2018}, author = {Bangs, MR and Douglas, MR and Mussmann, SM and Douglas, ME}, title = {Unraveling historical introgression and resolving phylogenetic discord within Catostomus (Osteichthys: Catostomidae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {86}, pmid = {29879898}, issn = {1471-2148}, mesh = {Animals ; Cypriniformes/*classification/genetics ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Geography ; *Phylogeny ; Species Specificity ; United States ; }, abstract = {BACKGROUND: Porous species boundaries can be a source of conflicting hypotheses, particularly when coupled with variable data and/or methodological approaches. Their impacts can often be magnified when non-model organisms with complex histories of reticulation are investigated. One such example is the genus Catostomus (Osteichthys, Catostomidae), a freshwater fish clade with conflicting morphological and mitochondrial phylogenies. The former is hypothesized as reflecting the presence of admixed genotypes within morphologically distinct lineages, whereas the latter is interpreted as the presence of distinct morphologies that emerged multiple times through convergent evolution. We tested these hypotheses using multiple methods, to including multispecies coalescent and concatenated approaches. Patterson's D-statistic was applied to resolve potential discord, examine introgression, and test the putative hybrid origin of two species. We also applied naïve binning to explore potential effects of concatenation.

RESULTS: We employed 14,007 loci generated from ddRAD sequencing of 184 individuals to derive the first highly supported nuclear phylogeny for Catostomus. Our phylogenomic analyses largely agreed with a morphological interpretation,with the exception of the placement of Xyrauchen texanus, which differs from both morphological and mitochondrial phylogenies. Additionally, our evaluation of the putative hybrid species C. columbianus revealed a lack introgression and instead matched the mitochondrial phylogeny. Furthermore, D-statistic tests clarified all discrepancies based solely on mitochondrial data, with agreement among topologies derived from concatenation and multispecies coalescent approaches. Extensive historic introgression was detected across six species-pairs. Potential endemism in the Virgin and Little Colorado Rivers was also apparent, and the former genus Pantosteus was derived as monophyletic, save for C. columbianus.

CONCLUSIONS: Complex reticulated histories detected herein support the hypothesis that introgression was responsible for conflicts that occurred within the mitochondrial phylogeny, and explains discrepancies found between it and previous morphological phylogenies. Additionally, the hybrid origin of C. columbianus was refuted, but with the caveat that more fine-grain sampling is still needed. Our diverse phylogenomic approaches provided largely concordant results, with naïve binning useful in exploring the single conflict. Considerable diversity was found within Catostomus across southwestern North America, with two drainages [Virgin River (UT) and Little Colorado River (AZ)] reflecting unique composition.}, } @article {pmid29879897, year = {2018}, author = {Hein, A and Knoop, V}, title = {Expected and unexpected evolution of plant RNA editing factors CLB19, CRR28 and RARE1: retention of CLB19 despite a phylogenetically deep loss of its two known editing targets in Poaceae.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {85}, pmid = {29879897}, issn = {1471-2148}, mesh = {Arabidopsis/genetics ; Base Sequence ; Cell Nucleus/metabolism ; Chloroplasts/genetics ; *Evolution, Molecular ; Mitochondria/genetics ; *Phylogeny ; Plant Proteins/*genetics/metabolism ; Poaceae/*genetics ; RNA Editing/*genetics ; RNA, Messenger/genetics/metabolism ; RNA, Plant/*genetics/metabolism ; RNA-Binding Proteins/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: C-to-U RNA editing in mitochondria and chloroplasts and the nuclear-encoded, RNA-binding PPR proteins acting as editing factors present a wide field of co-evolution between the different genetic systems in a plant cell. Recent studies on chloroplast editing factors RARE1 and CRR28 addressing one or two chloroplast editing sites, respectively, found them strictly conserved among 65 flowering plants as long as one of their RNA editing targets remained present.

RESULTS: Extending the earlier sampling to 117 angiosperms with high-quality genome or transcriptome data, we find more evidence confirming previous conclusions but now also identify cases for expected evolutionary transition states such as retention of RARE1 despite loss of its editing target or the degeneration of CRR28 truncating its carboxyterminal DYW domain. The extended angiosperm set was now used to explore CLB19, an "E+"-type PPR editing factor targeting two chloroplast editing sites, rpoAeU200SF and clpPeU559HY, in Arabidopsis thaliana. We found CLB19 consistently conserved if one of the two targets was retained and three independent losses of CLB19 after elimination of both targets. The Ericales show independent regains of the ancestrally lost clpPeU559HY editing, further explaining why multiple-target editing factors are lost much more rarely than single target factors like RARE1. The retention of CLB19 despite loss of both editing targets in some Ericaceae, Apocynaceae and in Camptotheca (Nyssaceae) likely represents evolutionary transitions. However, the retention of CLB19 after a phylogenetic deep loss in the Poaceae rather suggests a yet unrecognized further editing target, for which we suggest editing event ndhAeU473SL.

CONCLUSION: Extending the scope of studies on plant organelle RNA editing to further taxa and additional nuclear cofactors reveals expected evolutionary transitions, strikingly different evolutionary dynamics for multiple-target editing factors like CLB19 and CRR28 and suggests additional functions for editing factor CLB19 among the Poaceae.}, } @article {pmid29879896, year = {2018}, author = {Böhmer, C and Amson, E and Arnold, P and van Heteren, AH and Nyakatura, JA}, title = {Homeotic transformations reflect departure from the mammalian 'rule of seven' cervical vertebrae in sloths: inferences on the Hox code and morphological modularity of the mammalian neck.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {84}, pmid = {29879896}, issn = {1471-2148}, support = {DFG EXC 1027//Deutsche Forschungsgemeinschaft/International ; DFG AM 517/1-1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Animals ; Biological Evolution ; Cervical Vertebrae/*anatomy & histology ; Databases as Topic ; *Genes, Homeobox ; Sloths/*anatomy & histology/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: Sloths are one of only two exceptions to the mammalian 'rule of seven' vertebrae in the neck. As a striking case of breaking the evolutionary constraint, the explanation for the exceptional number of cervical vertebrae in sloths is still under debate. Two diverging hypotheses, both ultimately linked to the low metabolic rate of sloths, have been proposed: hypothesis 1 involves morphological transformation of vertebrae due to changes in the Hox gene expression pattern and hypothesis 2 assumes that the Hox gene expression pattern is not altered and the identity of the vertebrae is not changed. Direct evidence supporting either hypothesis would involve knowledge of the vertebral Hox code in sloths, but the realization of such studies is extremely limited. Here, on the basis of the previously established correlation between anterior Hox gene expression and the quantifiable vertebral shape, we present the morphological regionalization of the neck in three different species of sloths with aberrant cervical count providing indirect insight into the vertebral Hox code.

RESULTS: Shape differences within the cervical vertebral column suggest a mouse-like Hox code in the neck of sloths. We infer an anterior shift of HoxC-6 expression in association with the first thoracic vertebra in short-necked sloths with decreased cervical count, and a posterior shift of HoxC-5 and HoxC-6 expression in long-necked sloths with increased cervical count.

CONCLUSION: Although only future developmental analyses in non-model organisms, such as sloths, will yield direct evidence for the evolutionary mechanism responsible for the aberrant number of cervical vertebrae, our observations lend support to hypothesis 1 indicating that the number of modules is retained but their boundaries are displaced. Our approach based on quantified morphological differences also provides a reliable basis for further research including fossil taxa such as extinct 'ground sloths' in order to trace the pattern and the underlying genetic mechanisms in the evolution of the vertebral column in mammals.}, } @article {pmid29879895, year = {2018}, author = {Brüniche-Olsen, A and Westerman, R and Kazmierczyk, Z and Vertyankin, VV and Godard-Codding, C and Bickham, JW and DeWoody, JA}, title = {The inference of gray whale (Eschrichtius robustus) historical population attributes from whole-genome sequences.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {87}, pmid = {29879895}, issn = {1471-2148}, mesh = {Animals ; Atlantic Ocean ; Base Sequence ; Cluster Analysis ; Ecosystem ; Genetic Variation ; *Genome ; Geography ; Homozygote ; Inbreeding ; Pacific Ocean ; Population Density ; Statistics as Topic ; Whales/*genetics/*physiology ; }, abstract = {BACKGROUND: Commercial whaling caused extensive demographic declines in many great whale species, including gray whales that were extirpated from the Atlantic Ocean and dramatically reduced in the Pacific Ocean. The Eastern Pacific gray whale has recovered since the 1982 ban on commercial whaling, but the Western Pacific gray whale-once considered possibly extinct-consists of only about 200 individuals and is considered critically endangered by some international authorities. Herein, we use whole-genome sequencing to investigate the demographic history of gray whales from the Pacific and use environmental niche modelling to make predictions about future gene flow.

RESULTS: Our sequencing efforts and habitat niche modelling indicate that: i) western gray whale effective population sizes have declined since the last glacial maximum; ii) contemporary gray whale genomes, both eastern and western, harbor less autosomal nucleotide diversity than most other marine mammals and megafauna; iii) the extent of inbreeding, as measured by autozygosity, is greater in the Western Pacific than in the Eastern Pacific populations; and iv) future climate change is expected to open new migratory routes for gray whales.

CONCLUSION: Our results indicate that gray whale genomes contain low nucleotide diversity and have been subject to both historical and recent inbreeding. Population sizes over the last million years likely peaked about 25,000 years before present and have declined since then. Our niche modelling suggests that novel migratory routes may develop within the next century and if so this could help retain overall genetic diversity, which is essential for adaption and successful recovery in light of global environmental change and past exploitation.}, } @article {pmid29879705, year = {2018}, author = {Hatano, M and Fukuzawa, R and Hasegawa, Y}, title = {The Mosaicism Ratio of 45,X May Explain the Phenotype in a Case of Mixed Gonadal Dysgenesis.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {4}, pages = {175-179}, doi = {10.1159/000489451}, pmid = {29879705}, issn = {1661-5433}, mesh = {Adolescent ; Aorta/pathology ; Child ; Child, Preschool ; Gonadal Dysgenesis, Mixed/*pathology ; Gonads/pathology/surgery ; Humans ; Infant ; Infant, Newborn ; Male ; *Mosaicism ; Mullerian Ducts/pathology ; Phenotype ; Turner Syndrome/*pathology ; }, abstract = {Some patients with mixed gonadal dysgenesis (MGD), whose prototypical karyotype is 45,X/46,XY, are known to manifest complications characteristic of Turner syndrome. We report a 16-year-old social male with MGD presenting with coarctation of the aorta, one of the common complications for Turner syndrome. At birth, the patient was found to have hypospadias, bifid scrotum, and cryptorchidism. Chromosomal analysis of his lymphocytes revealed the karyotype 45,X[7]/46,X,dic(Y;22)(p11.3;q13.3)[23] (named 45,X/46,X+Y fragment in this article). A left gonadectomy was performed at 1 year of age, and the histology showed a streak gonad with an epithelial cord-like structure compatible with MGD. At the age of 10 years, coarctation of the aorta was discovered by chance, for which the patient underwent surgical repair. The ratio of mosaicism in the gonad and aortic tissues was estimated by FISH with probes to identify the X centromere-specific repeat sequence and Yp11.2. The mosaicism ratio of 45,X/46,X+Y fragment varied among the tissues, with those having a higher ratio being more likely to exhibit the Turner syndrome phenotype. Some 90% of cells in the aortic tissues and 80% in the gonadal tissues lacked a Y chromosome. In conclusion, the mosaicism ratio in the different tissues may explain the phenotypes in MGD.}, } @article {pmid29879699, year = {2018}, author = {Caetano de Barros, L and Piscor, D and Parise-Maltempi, PP and Feldberg, E}, title = {Differentiation and Evolution of the W Chromosome in the Fish Species of Megaleporinus (Characiformes, Anostomidae).}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {4}, pages = {204-209}, doi = {10.1159/000489693}, pmid = {29879699}, issn = {1661-5433}, mesh = {Animals ; Characiformes/*genetics ; *Evolution, Molecular ; Female ; In Situ Hybridization, Fluorescence ; Male ; Metaphase ; Sex Chromosomes/*genetics ; }, abstract = {The W chromosome of Megaleporinus trifasciatus was isolated in order to analyze its behavior in the karyotype of this and other species of the family, including forms with differentiated and undifferentiated sex chromosomes. The chromosome was microdissected, and the WMt probe was prepared for the chromosome painting procedure. M. trifasciatus was also cross-hybridized (cross-FISH) using existing probes available for M. macrocephalus (WMm) and M. elongatus (WMe). Two Leporinus species and Semaprochilodus taeniurus, representing a clade close to the Anostomidae, were also cross-hybridized with the objective to better understand the evolution of the sex chromosomes. In the metaphase of female M. trifasciatus, the WMt probe highlighted the whole long arm of the W chromosome and a small, distal portion of the long arm of the Z chromosome. In males, the probe highlighted the distal portion of the long arm of the Z chromosomes. The hybridization of female M. trifasciatus with the WMe and WMm probes revealed a pattern similar to that encountered using the WMt probe. The WMt, WMm, and WMe probes revealed broad similarities among the species of the genus Megaleporinus, which has a ZZ/ZW system of sex chromosomes, with only minor alterations becoming apparent when analyzed separately.}, } @article {pmid29879621, year = {2018}, author = {Bruger, EL and Marx, CJ}, title = {A decade of genome sequencing has revolutionized studies of experimental evolution.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {149-155}, doi = {10.1016/j.mib.2018.03.002}, pmid = {29879621}, issn = {1879-0364}, abstract = {Genome sequencing has revolutionized studies using experimental evolution of microbes because it readily provides comprehensive insight into the genetic bases of adaptation. In this perspective we discuss applications of sequencing-based technologies used to study evolution in microbes, including genomic sequencing of isolated evolved clones and mixed evolved populations, and also the use of sequencing methods to follow the fate of introduced variations, whether neutral barcodes or variants introduced by genome editing. Collectively, these sequencing-based approaches have vastly advanced the examination of evolution in the lab, as well as begun to synthesize this work with examination of the genetic bases of adaptation and evolutionary dynamics within natural populations.}, } @article {pmid29879468, year = {2018}, author = {Díaz-Pérez, A and López-Álvarez, D and Sancho, R and Catalán, P}, title = {Reconstructing the origins and the biogeography of species' genomes in the highly reticulate allopolyploid-rich model grass genus Brachypodium using minimum evolution, coalescence and maximum likelihood approaches.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {256-271}, doi = {10.1016/j.ympev.2018.06.003}, pmid = {29879468}, issn = {1095-9513}, abstract = {The identification of homeologous genomes and the biogeographical analyses of highly reticulate allopolyploid-rich groups face the challenge of incorrectly inferring the genomic origins and the biogeographical patterns of the polyploids from unreliable strictly bifurcating trees. Here we reconstruct a plausible evolutionary scenario of the diverging and merging genomes inherited by the diploid and allopolyploid species and cytotypes of the model grass genus Brachypodium. We have identified the ancestral Brachypodium genomes and inferred the paleogeographical ranges for potential hybridization events that originated its allopolyploid taxa. We also constructed a comprehensive phylogeny of Brachypodium from five nuclear and plastid genes using Species Tree Minimum Evolution allele grafting and Species Network analysis. The divergence ages of the lineages were estimated from a consensus maximum clade credibility tree using fossil calibrations, whereas ages of origin of the diploid and allopolyploid species were inferred from coalescence Bayesian methods. The biogeographical events of the genomes were reconstructed using a stratified Dispersal-Extinction-Colonization model with three temporal windows. Our combined Minimum Evolution-coalescence-Bayesian approach allowed us to infer the origins and the identities of the homeologous genomes of the Brachypodium allopolyploids, matching the expected ploidy levels of the hybrids. To date, the current extant progenitor genomes (species) are only known for B. hybridum. Putative ancestral homeologous genome have been inherited by B. mexicanum, ancestral and recent genomes by B. boissieri, and only recently evolved genomes by B. retusum and the core perennial clade allopolyploids (B. phoenicoides, B. pinnatum 4x, B. rupestre 4x). We dissected the complex spatio-temporal evolution of ancestral and recent genomes and have detected successive splitting, dispersal and merging events for dysploid homeologous genomes in diverse geographical scenarios that have led to the current extant taxa. Our data support Mid-Miocene splits of the Holarctic ancestral genomes that preceded the Late Miocene origins of Brachypodium ancestors of the modern diploid species. Successive divergences of the annual B. stacei and B. distachyon diploid genomes were implied to have occurred in the Mediterranean region during the Late Miocene-Pliocene. By contrast, a profusion of splits, range expansions and different genome mergings were inferred for the perennial diploid genomes in the Mediterranean and Eurasian regions, with sporadic colonizations and further mergings in other continents during the Quaternary. A reliable biogeographical scenario was obtained for the Brachypodium genomes and allopolyploids where homeologous genomes split from their respective diploid counterpart lineages in the same ancestral areas, showing similar or distinct dispersals. By contrast, the allopolyploid taxa remained in the same ancestral ranges after hybridization and genome doubling events. Our approach should have utility in deciphering the genomic composition and the historical biogeography of other allopolyploid-rich organismal groups, which are predominant in eukaryotes.}, } @article {pmid29878552, year = {2018}, author = {Wackett, LP}, title = {Microbial enrichment culturing: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {394-395}, doi = {10.1111/1758-2229.12658}, pmid = {29878552}, issn = {1758-2229}, } @article {pmid29878227, year = {2018}, author = {Bürgmann, H and Frigon, D and H Gaze, W and M Manaia, C and Pruden, A and Singer, AC and F Smets, B and Zhang, T}, title = {Water and sanitation: an essential battlefront in the war on antimicrobial resistance.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {9}, pages = {}, doi = {10.1093/femsec/fiy101}, pmid = {29878227}, issn = {1574-6941}, abstract = {Water and sanitation represent a key battlefront in combatting the spread of antimicrobial resistance (AMR). Basic water sanitation infrastructure is an essential first step towards protecting public health, thereby limiting the spread of pathogens and the need for antibiotics. AMR presents unique human health risks, meriting new risk assessment frameworks specifically adapted to water and sanitation-borne AMR. There are numerous exposure routes to AMR originating from human waste, each of which must be quantified for its relative risk to human health. Wastewater treatment plants play a vital role in centralized collection and treatment of human sewage, but there are numerous unresolved issues in terms of the microbial ecological processes occurring within them and the extent to which they attenuate or amplify AMR. Research is needed to advance understanding of the fate of resistant bacteria and antibiotic resistance genes in various waste management systems, depending on the local constraints and intended reuse applications. World Health Organization and national AMR action plans would benefit from a more holistic 'One Water' understanding. In this article we provide a framework for research, policy, practice and public engagement aimed at limiting the spread of AMR from water and sanitation in low-, medium- and high-income countries.}, } @article {pmid29878203, year = {2018}, author = {Battistuzzi, FU and Tao, Q and Jones, L and Tamura, K and Kumar, S}, title = {RelTime Relaxes the Strict Molecular Clock throughout the Phylogeny.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1631-1636}, pmid = {29878203}, issn = {1759-6653}, support = {R01 GM126567/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; Computer Simulation ; Evolution, Molecular ; Fossils ; Genetic Speciation ; Genetic Variation/*genetics ; Models, Genetic ; Phylogeny ; Time Factors ; }, abstract = {The RelTime method estimates divergence times when evolutionary rates vary among lineages. Theoretical analyses show that RelTime relaxes the strict molecular clock throughout a molecular phylogeny, and it performs well in the analyses of empirical and computer simulated data sets in which evolutionary rates are variable. Lozano-Fernandez et al. (2017) found that the application of RelTime to one metazoan data set (Erwin et al. 2011) produced equal rates for several ancient lineages, which led them to speculate that RelTime imposes a strict molecular clock for deep animal divergences. RelTime does not impose a strict molecular clock. The pattern observed by Lozano-Fernandez et al. (2017) was a result of the use of an option to assign the same rate to lineages in RelTime when the rates are not statistically significantly different. The median rate difference was 5% for many deep metazoan lineages for the Erwin et al. (2011) data set, so the rate equality was not rejected. In fact, RelTime analyses with and without the option to test rate differences produced very similar time estimates. We also found that the Bayesian time estimates vary widely depending on the root priors assigned, and that the use of less restrictive priors produces Bayesian divergence times that are concordant with those from RelTime for the Erwin et al. (2011) data set. Therefore, it is prudent to discuss Bayesian estimates obtained under a range of priors in any discourse about molecular dating, including method comparisons.}, } @article {pmid29878200, year = {2018}, author = {Lee, FJ and Miller, KI and McKinlay, JB and Newton, ILG}, title = {Differential carbohydrate utilization and organic acid production by honey bee symbionts.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy113}, pmid = {29878200}, issn = {1574-6941}, abstract = {The honey bee worker gut hosts a community of bacteria that comprises 8-10 core bacterial species, along with a set of more transient environmental microbes. Collectively, these microbes break down and ferment saccharides present in the host's diet, based on analyses of metagenomes, and metatranscriptomes from this environment. As part of this metabolism, the bacteria produce short-chain fatty acids that may serve as a food source for the host bee, stimulating biological processes that may contribute to host weight gain. To identify metabolic contributions of symbionts within the honey bee gut, we utilized a combination of molecular and biochemical approaches. We show significant variation in the metabolic capabilities of honey bee-associated taxa, highlighting the fact that honey bee gut microbiota members of the same clade are highly variable in their ability to use specific carbohydrates and produce organic acids. Finally, we confirm that the honey bee core microbes are active in vivo, expressing key enzymatic genes critical for utilizing plant-derived molecules and producing organic acids (i.e. acetate and lactate). These results suggest that core taxa may contribute significantly to weight gain in the honey bee, specifically through the production of organic acids.}, } @article {pmid29878195, year = {2018}, author = {Newsome, L and Lopez Adams, R and Downie, HF and Moore, KL and Lloyd, JR}, title = {NanoSIMS imaging of extracellular electron transport processes during microbial iron(III) reduction.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, pmid = {29878195}, issn = {1574-6941}, abstract = {Microbial iron(III) reduction can have a profound effect on the fate of contaminants in natural and engineered environments. Different mechanisms of extracellular electron transport are used by Geobacter and Shewanella spp. to reduce insoluble Fe(III) minerals. Here we prepared a thin film of iron(III)-(oxyhydr)oxide doped with arsenic, and allowed the mineral coating to be colonised by Geobacter sulfurreducens or Shewanella ANA3 labelled with 13C from organic electron donors. This preserved the spatial relationship between metabolically active Fe(III)-reducing bacteria and the iron(III)-(oxyhydr)oxide that they were respiring. NanoSIMS imaging showed cells of G. sulfurreducens were co-located with the iron(III)-(oxyhydr)oxide surface and were significantly more 13C-enriched compared to cells located away from the mineral, consistent with Geobacter species requiring direct contact with an extracellular electron acceptor to support growth. There was no such intimate relationship between 13C-enriched S. ANA3 and the iron(III)-(oxyhydr)oxide surface, consistent with Shewanella species being able to reduce Fe(III) indirectly using a secreted endogenous mediator. Some differences were observed in the amount of As relative to Fe in the local environment of G. sulfurreducens compared to the bulk mineral, highlighting the usefulness of this type of analysis for probing interactions between microbial cells and Fe-trace metal distributions in biogeochemical experiments.}, } @article {pmid29878194, year = {2018}, author = {Brié, A and Gantzer, C and Boudaud, N and Bertrand, I}, title = {The impact of chlorine and heat on the infectivity and physicochemical properties of bacteriophage MS2.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy106}, pmid = {29878194}, issn = {1574-6941}, abstract = {Enteric viruses and bacteriophages are exposed to various inactivating factors outside their host, and among them chlorine and heat are the most commonly used sanitizer in water industry and treatment in the food industry, respectively. Using MS2 phages as models for enteric viruses, we investigated the impact of free chlorine and heat on their physicochemical properties. Free chlorine was first evaluated alone. No increase in either capsid permeability or hydrophobicity was observed. The negative surface charge slightly increased suggesting molecular changes in the capsid. However, a weakening of the capsid by chlorine was suggested by differential scanning fluorimetry. This phenomenon was confirmed when chlorination was followed by a heat treatment. Indeed, an increase in the inactivation of MS2 phages and the permeability of their capsids to RNases was observed. More interestingly, an increase in the expression of hydrophobic domains at the phage surface was observed, but only for phages remaining infectious. The chlorine-caused weakening of the capsid suggested that, for an optimal use, the oxidant should be followed by heat. The increased permeability to RNases and the expression of hydrophobic domains may contribute to the development or improvement of molecular methods specific for infectious enteric viruses.}, } @article {pmid29878192, year = {2018}, author = {Pinzari, F and Cuadros, J and Migliore, M and Napoli, R and Najorka, J}, title = {Manganese translocation and concentration on Quercus cerris decomposing leaf and wood litter by an ascomycetous fungus: an active process with ecosystem consequences?.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy111}, pmid = {29878192}, issn = {1574-6941}, abstract = {Decomposing fungi translocate manganese (Mn) as demonstrated by the fact that Mn has been found to accumulate on decomposing leaves associated with individual fungal hyphae forming insoluble Mn(III,IV) oxides that remain concentrated in diffuse patches. Here, we studied Mn translocation and precipitation by the saprophytic fungus Alternaria sp. strain FBL507 both on naturally decomposing oak leaves and in vitro experiments. Manganese was translocated and precipitated in beads and encrustations along the fungal hyphae. The combination of X-ray diffraction and scanning electron microscopy-energy dispersive X-ray spectroscopy chemical data showed that the precipitates found on leaves were rhodochrosite (MnCO3), birnessite ([Na, Ca, K]Mn2O4× 1.5H2O) and possibly Mn oxalate. The precipitates on wood were an amorphous Mn-O compound, probably MnO. Thus, Mn oxidation state in the precipitates spanned from +2 to +4, with +3 and +4 only in the birnessite on the leaves. In vitro experiments showed that Mn precipitates formed in living hyphae, suggesting the possibility that Mn precipitation is actively produced by the fungus. Such a possibility raises interesting questions regarding the role of readily available Mn in the activity of saprophytic fungi and other soil microorganisms, such as would result in a large involvement of Mn in the cycles of the major nutrient elements.}, } @article {pmid29878184, year = {2018}, author = {Torres-Barceló, C and Gurney, J and Gougat-Barberá, C and Vasse, M and Hochberg, ME}, title = {Transient negative effects of antibiotics on phages do not jeopardise the advantages of combination therapies.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy107}, pmid = {29878184}, issn = {1574-6941}, abstract = {Phages, the viruses of bacteria, have been proposed as antibacterial agents to complement or replace antibiotics due to the growing problem of resistance. In nature and in the clinic, antibiotics are ubiquitous and may affect phages indirectly via impacts on bacterial hosts. Even if the synergistic association of phages and antibiotics has been shown in several studies, the focus is often on bacteria with little known about the impact on phages. Evolutionary studies have demonstrated that time scale is an important factor in understanding the consequences of antimicrobial strategies, but this perspective is generally overlooked in phage-antibiotic combination studies. Here, we explore the effects of antibiotics on phages targeting the opportunistic pathogen Pseudomonas aeruginosa. We go beyond previous studies by testing the interaction between several types of antibiotics and phages, and evaluate the effects on several important phage parameters during 8 days of experimental co-evolution with bacteria. Our study reveals that antibiotics had a negative effect on phage density and efficacy early on, but not in the later stages of the experiment. The results indicate that antibiotics can affect phage adaptation, but that phages can nevertheless contribute to managing antibiotic resistance levels.}, } @article {pmid29878181, year = {2018}, author = {Renaut, S and Guerra, D and Hoeh, WR and Stewart, DT and Bogan, AE and Ghiselli, F and Milani, L and Passamonti, M and Breton, S}, title = {Genome Survey of the Freshwater Mussel Venustaconcha ellipsiformis (Bivalvia: Unionida) Using a Hybrid De Novo Assembly Approach.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1637-1646}, pmid = {29878181}, issn = {1759-6653}, mesh = {Animals ; Chromosome Mapping/methods ; DNA, Mitochondrial/*genetics ; Genes, Mitochondrial ; Genome ; Genome Size ; *Genome, Mitochondrial ; Genomics/*methods ; Heterozygote ; High-Throughput Nucleotide Sequencing/methods ; Polymorphism, Genetic ; Unionidae/*genetics ; }, abstract = {Freshwater mussels (Bivalvia: Unionida) serve an important role as aquatic ecosystem engineers but are one of the most critically imperilled groups of animals. Here, we used a combination of sequencing strategies to assemble and annotate a draft genome of Venustaconcha ellipsiformis, which will serve as a valuable genomic resource given the ecological value and unique "doubly uniparental inheritance" mode of mitochondrial DNA transmission of freshwater mussels. The genome described here was obtained by combining high-coverage short reads (65× genome coverage of Illumina paired-end and 11× genome coverage of mate-pairs sequences) with low-coverage Pacific Biosciences long reads (0.3× genome coverage). Briefly, the final scaffold assembly accounted for a total size of 1.54 Gb (366,926 scaffolds, N50 = 6.5 kb, with 2.3% of "N" nucleotides), representing 86% of the predicted genome size of 1.80 Gb, while over one third of the genome (37.5%) consisted of repeated elements and >85% of the core eukaryotic genes were recovered. Given the repeated genetic bottlenecks of V. ellipsiformis populations as a result of glaciations events, heterozygosity was also found to be remarkably low (0.6%), in contrast to most other sequenced bivalve species. Finally, we reassembled the full mitochondrial genome and found six polymorphic sites with respect to the previously published reference. This resource opens the way to comparative genomics studies to identify genes related to the unique adaptations of freshwater mussels and their distinctive mitochondrial inheritance mechanism.}, } @article {pmid29878153, year = {2018}, author = {Larter, M and Dunbar-Wallis, A and Berardi, AE and Smith, SD}, title = {Convergent evolution at the pathway level: predictable regulatory changes during flower color transitions.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy117}, pmid = {29878153}, issn = {1537-1719}, abstract = {The predictability of evolution, or whether lineages repeatedly follow the same evolutionary trajectories during phenotypic convergence remains an open question of evolutionary biology. In this study, we investigate evolutionary convergence at the biochemical pathway level and test the predictability of evolution using floral anthocyanin pigmentation, a trait with a well-understood genetic and regulatory basis. We reconstructed the evolution of floral anthocyanin content across 28 species of the Andean clade Iochrominae (Solanaceae) and investigated how shifts in pigmentation are related to changes in expression of 7 key anthocyanin pathway genes. We used phylogenetic multivariate analysis of gene expression to test for phenotypic and developmental convergence at a macroevolutionary scale. Our results show that the four independent losses of the ancestral pigment delphinidin involved convergent losses of expression of the three late pathway genes (F3'5'h, Dfr and Ans). Transitions between pigment types affecting floral hue (e.g. blue to red) involve changes to the expression of branching genes F3'h and F3'5'h, while the expression levels of early steps of the pathway are strongly conserved in all species. These patterns support the idea that the macroevolution of floral pigmentation follows predictable evolutionary trajectories to reach convergent phenotype space, repeatedly involving regulatory changes. This is likely driven by constraints at the pathway level, such as pleiotropy and regulatory structure.}, } @article {pmid29878143, year = {2018}, author = {Russo, CAM and Selvatti, AP}, title = {Bootstrap and rogue identification tests for phylogenetic analyses.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy118}, pmid = {29878143}, issn = {1537-1719}, abstract = {Most phylogenetic tree-generating programs produce a fully dichotomous phylogenetic tree. However, as different markers may produce distinct topologies for the same set of organisms, topological tests are used to estimate the statistical reliability of the clades. In this protocol, we provide step-by-step instructions on how to perform the widely used bootstrap test using MEGA. However, a single unstable lineage, also known as a rogue lineage, may decrease the bootstrap proportions in many branches of the tree. This occurs because rogue taxa tend to bounce between clades from one pseudo-replicate to the next, lowering bootstrap proportions for many correct clades. Thus, it is important to identify and exclude rogue taxa before initiating a final phylogenetic analysis; here, we provide this protocol using the RogueNaRok platform.}, } @article {pmid29878114, year = {2018}, author = {Vishnivetskaya, TA and Buongiorno, J and Bird, J and Krivushin, K and Spirina, EV and Oshurkova, V and Shcherbakova, VA and Wilson, G and Lloyd, KG and Rivkina, EM}, title = {Methanogens in the Antarctic Dry Valley permafrost.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy109}, pmid = {29878114}, issn = {1574-6941}, abstract = {Polar permafrost is at the forefront of climate change, yet only a few studies have enriched the native methane-producing microbes that might provide positive feedbacks to climate change. Samples Ant1 and Ant2, collected in Antarctic Miers Valley from permafrost sediments, with and without biogenic methane, respectively, were evaluated for methanogenic activity and presence of methanogens. After a one-year incubation of both samples under anaerobic conditions, methane production was observed only at room temperature in microcosm Ant1 with CO2/H2 (20/80) as carbon and energy sources and was monitored during the subsequent 10 years. The concentration of methane in the headspace of microcosm Ant1 changed from 0.8% to a maximum of 45%. Archaeal 16S rRNA genes from microcosm Ant1 were related to psychrotolerant Methanosarcina lacustris. Repeated efforts at achieving a pure culture of this organism were unsuccessful. Metagenomic reads obtained for the methane-producing microcosm Ant1 were assembled and resulted in a 99.84% complete genome affiliated with the genus Methanosarcina. The metagenome assembled genome contained cold-adapted enzymes and pathways suggesting that the novel uncultured Methanosarcina sp. Ant1 is adapted to sub-freezing conditions in permafrost. This is the first methanogen genome reported from the 15 000 years old permafrost of the Antarctic Dry Valleys.}, } @article {pmid29878113, year = {2018}, author = {Manirajan, BA and Maisinger, C and Ratering, S and Rusch, V and Schwiertz, A and Cardinale, M and Schnell, S}, title = {Diversity, specificity, co-occurrence and hub taxa of the bacterial-fungal pollen microbiome.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy112}, pmid = {29878113}, issn = {1574-6941}, abstract = {Flower pollen represents a unique microbial habitat, however the factors driving microbial assemblages and microbe-microbe interactions remain largely unexplored. Here we compared the structure and diversity of the bacterial-fungal microbiome between eight different pollen species (four wind-pollinated and four insect-pollinated) from close geographical locations, using high-throughput sequencing of the 16S the rRNA gene fragment (bacteria) and the internal transcribed spacer 2 (ITS2, fungi). Proteobacteria and Ascomycota were the most abundant bacterial and fungal phyla, respectively. Pseudomonas (bacterial) and Cladosporium (fungal) were the most abundant genera. Both bacterial and fungal microbiota were significantly influenced by plant species and pollination type, but showed a core microbiome consisting of 12 bacterial and 33 fungal genera. Co-occurrence analysis highlighted significant inter- and intra-kingdom interactions, and the interaction network was shaped by four bacterial hub taxa: Methylobacterium (two OTUs), Friedmanniella and Rosenbergiella. Rosenbergiella prevailed in insect-pollinated pollen and was negatively correlated with the other hubs, indicating habitat complementarity. Inter-kingdom co-occurrence showed a predominant effect of fungal on bacterial taxa. This study enhances our basic knowledge of pollen microbiota, and poses the basis for further inter- and intra-kingdom interaction studies in the plant reproductive organs.}, } @article {pmid29878107, year = {2018}, author = {Cellamare, M and Duval, C and Drelin, Y and Djediat, C and Touibi, N and Agogué, H and Leboulanger, C and Ader, M and Bernard, C}, title = {Characterization of phototrophic microorganisms and description of new cyanobacteria isolated from the saline-alkaline crater-lake Dziani Dzaha (Mayotte, Indian Ocean).}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy108}, pmid = {29878107}, issn = {1574-6941}, abstract = {The saline-alkaline crater-lake Dziani Dzaha (Mayotte, Indian Ocean) is dominated by the bloom-forming cyanobacterium Arthrospira. However, the rest of the phototrophic community remains underexplored because of their minute dimension or lower biomass. To characterize the phototrophic microorganisms living in this ecosystem considered as a modern analog of Precambrian environments, several strains were isolated from the water column and stromatolites and analyzed using the polyphasic approach. Based on morphological, ultrastructural and molecular (16S rRNA gene, 18S rRNA gene, 16S-23S internal transcribed spacer (ITS) region and cpcBA-IGS locus) methods, seven filamentous cyanobacteria and the prasinophyte Picocystis salinarum were identified. Two new genera and four new cyanobacteria species belonging to the orders Oscillatoriales (Desertifilum dzianense sp. nov.) and Synechococcales (Sodalinema komarekii gen. nov., sp. nov., Sodaleptolyngbya stromatolitii gen. nov., sp. nov. and Haloleptolyngbya elongata sp. nov.) were described. This approach also allowed to identify Arthrospira fusiformis with exclusively straight trichomes instead of the spirally coiled form commonly observed in the genus. This study evidenced the importance of using the polyphasic approach to solve the complex taxonomy of cyanobacteria and to study algal assemblages from unexplored ecosystems.}, } @article {pmid29877789, year = {2018}, author = {Machado, RAR and Wüthrich, D and Kuhnert, P and Arce, CCM and Thönen, L and Ruiz, C and Zhang, X and Robert, CAM and Karimi, J and Kamali, S and Ma, J and Bruggmann, R and Erb, M}, title = {Whole-genome-based revisit of Photorhabdus phylogeny: proposal for the elevation of most Photorhabdus subspecies to the species level and description of one novel species Photorhabdus bodei sp. nov., and one novel subspecies Photorhabdus laumondii subsp. clarkei subsp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {8}, pages = {2664-2681}, doi = {10.1099/ijsem.0.002820}, pmid = {29877789}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; *Genome, Bacterial ; Nucleic Acid Hybridization ; Photorhabdus/*classification/genetics ; *Phylogeny ; Rhabditoidea/*microbiology ; Sequence Analysis, DNA ; Symbiosis ; }, abstract = {Bacterial symbionts are crucial for the infectivity and success of entomopathogenic nematodes as biological control agents. The current understanding of the symbiotic relationships is limited by taxonomic uncertainties. Here, we used whole-genome sequencing and traditional techniques to reconstruct the phylogenetic relationships between all described Photorhabdus species and subspecies as well as 11 newly isolated symbiotic bacteria of Heterorhabditis nematodes, including the unreported bacterial partner of H. beicherriana. In silico DNA-DNA hybridization, orthologous average nucleotide identity and nucleotide sequence identity of concatenated housekeeping genes scores were calculated and set into relation with current cut-off values for species delimitation in bacteria. Sequence data were complemented with biochemical and chemotaxonomic markers, and ribosomal protein fingerprinting profiles. This polyphasic approach resolves the ambiguous taxonomy of Photorhabdusand lead to the proposal for the elevation of most of them into a higher taxon and the creation of several new taxa: 15 new species, one of which is newly described: Photorhabdus bodei sp. nov. (type strain LJ24-63T=DSM 105690T=CCOS 1159T) and the other 14 arise through the proposal of elevating already described subspecies to species, and are proposed to be renamed as follows: Photorhabdus asymbioticasubsp. australis as Photorhabdus australis sp. nov., Photorhabdus luminescenssubsp. akhurstii as Photorhabdus akhurstii sp. nov., Photorhabdus luminescenssubsp. caribbeanensis as Photorhabdus caribbeanensis sp. nov., Photorhabdus luminescenssubsp. hainanensis as Photorhabdus hainanensis sp. nov., Photorhabdus luminescenssubsp. kayaii as Photorhabdus kayaii sp. nov., Photorhabdus luminescenssubsp. kleinii as Photorhabdus kleinii sp. nov., Photorhabdus luminescenssubsp. namnaonensis as Photorhabdus namnaonensis sp. nov., Photorhabdus luminescenssubsp. noenieputensis as Photorhabdus noenieputensis sp. nov., Photorhabdus luminescenssubsp.laumondii as Photorhabdus laumondii sp. nov., Photorhabdus temperatasubsp. cinerea as Photorhabdus cinerea sp. nov., Photorhabdus temperatasubsp. khanii as Photorhabdus khanii sp. nov., Photorhabdus temperatasubsp. stackebrandtii as Photorhabdus stackebrandtii sp. nov., Photorhabdus temperatasubsp. tasmaniensis as Photorhabdus tasmaniensis sp. nov., and Photorhabdus temperatasubsp. thracensis as Photorhabdus thracensis sp. nov. In addition, we propose the creation of two new subspecies, one of which arises through the reduction of rank: Photorhabdus laumondii subsp. laumondii comb. nov. (basonym: P. luminescenssubsp. laumondii) and the second one is newly described: Photorhabdus laumondii subsp. clarkei subsp. nov. (type strain BOJ-47T=DSM 105531T=CCOS 1160T). Finally, we propose to emend the description of three species, which results from the proposal of elevating three subspecies to the species status: Photorhabdus asymbiotica, Photorhabdus temperata and Photorhabdus luminescens, formerly classified as Photorhabdus asymbioticasubsp. asymbiotica, Photorhabdus temperatasubsp.temperata and Photorhabdus luminescenssubsp. luminescens, respectively.}, } @article {pmid29877021, year = {2018}, author = {Bestwick, J and Unwin, DM and Butler, RJ and Henderson, DM and Purnell, MA}, title = {Pterosaur dietary hypotheses: a review of ideas and approaches.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {2021-2048}, doi = {10.1111/brv.12431}, pmid = {29877021}, issn = {1469-185X}, abstract = {Pterosaurs are an extinct group of Mesozoic flying reptiles, whose fossil record extends from approximately 210 to 66 million years ago. They were integral components of continental and marginal marine ecosystems, yet their diets remain poorly constrained. Numerous dietary hypotheses have been proposed for different pterosaur groups, including insectivory, piscivory, carnivory, durophagy, herbivory/frugivory, filter-feeding and generalism. These hypotheses, and subsequent interpretations of pterosaur diet, are supported by qualitative (content fossils, associations, ichnology, comparative anatomy) and/or quantitative (functional morphology, stable isotope analysis) evidence. Pterosaur dietary interpretations are scattered throughout the literature with little attention paid to the supporting evidence. Reaching a robustly supported consensus on pterosaur diets is important for understanding their dietary evolution, and their roles in Mesozoic ecosystems. A comprehensive examination of the pterosaur literature identified 314 dietary interpretations (dietary statement plus supporting evidence) from 126 published studies. Multiple alternative diets have been hypothesised for most principal taxonomic pterosaur groups. Some groups exhibit a high degree of consensus, supported by multiple lines of evidence, while others exhibit less consensus. Qualitative evidence supports 87.3% of dietary interpretations, with comparative anatomy most common (62.1% of total). More speciose groups of pterosaur tend to have a greater range of hypothesised diets. Consideration of dietary interpretations within alternative phylogenetic contexts reveals high levels of consensus between equivalent monofenestratan groups, and lower levels of consensus between equivalent non-monofenestratan groups. Evaluating the possible non-biological controls on apparent patterns of dietary diversity reveals that numbers of dietary interpretations through time exhibit no correlation with patterns of publication (number of peer-reviewed publications through time). 73.8% of dietary interpretations were published in the 21st century. Overall, consensus interpretations of pterosaur diets are better accounted for by non-biological signals, such as the impact of the respective quality of the fossil record of different pterosaur groups on research levels. That many interpretations are based on qualitative, often untestable lines of evidence adds significant noise to the data. More experiment-led pterosaur dietary research, with greater consideration of pterosaurs as organisms with independent evolutionary histories, will lead to more robust conclusions drawn from repeatable results. This will allow greater understanding of pterosaur dietary diversity, disparity and evolution and facilitate reconstructions of Mesozoic ecosystems.}, } @article {pmid29877019, year = {2018}, author = {Schweiger, AH and Boulangeat, I and Conradi, T and Davis, M and Svenning, JC}, title = {The importance of ecological memory for trophic rewilding as an ecosystem restoration approach.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {}, number = {}, pages = {}, doi = {10.1111/brv.12432}, pmid = {29877019}, issn = {1469-185X}, abstract = {Increasing human pressure on strongly defaunated ecosystems is characteristic of the Anthropocene and calls for proactive restoration approaches that promote self-sustaining, functioning ecosystems. However, the suitability of novel restoration concepts such as trophic rewilding is still under discussion given fragmentary empirical data and limited theory development. Here, we develop a theoretical framework that integrates the concept of 'ecological memory' into trophic rewilding. The ecological memory of an ecosystem is defined as an ecosystem's accumulated abiotic and biotic material and information legacies from past dynamics. By summarising existing knowledge about the ecological effects of megafauna extinction and rewilding across a large range of spatial and temporal scales, we identify two key drivers of ecosystem responses to trophic rewilding: (i) impact potential of (re)introduced megafauna, and (ii) ecological memory characterising the focal ecosystem. The impact potential of (re)introduced megafauna species can be estimated from species properties such as lifetime per capita engineering capacity, population density, home range size and niche overlap with resident species. The importance of ecological memory characterising the focal ecosystem depends on (i) the absolute time since megafauna loss, (ii) the speed of abiotic and biotic turnover, (iii) the strength of species interactions characterising the focal ecosystem, and (iv) the compensatory capacity of surrounding source ecosystems. These properties related to the focal and surrounding ecosystems mediate material and information legacies (its ecological memory) and modulate the net ecosystem impact of (re)introduced megafauna species. We provide practical advice about how to quantify all these properties while highlighting the strong link between ecological memory and historically contingent ecosystem trajectories. With this newly established ecological memory-rewilding framework, we hope to guide future empirical studies that investigate the ecological effects of trophic rewilding and other ecosystem-restoration approaches. The proposed integrated conceptual framework should also assist managers and decision makers to anticipate the possible trajectories of ecosystem dynamics after restoration actions and to weigh plausible alternatives. This will help practitioners to develop adaptive management strategies for trophic rewilding that could facilitate sustainable management of functioning ecosystems in an increasingly human-dominated world.}, } @article {pmid29877015, year = {2018}, author = {Hsiung, AC and Boyle, WA and Cooper, RJ and Chandler, RB}, title = {Altitudinal migration: ecological drivers, knowledge gaps, and conservation implications.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {2049-2070}, doi = {10.1111/brv.12435}, pmid = {29877015}, issn = {1469-185X}, abstract = {Animal migration has been the subject of intensive research for more than a century, but most research has focused on long-distance rather than short-distance migration. Altitudinal migration is a form of short-distance migration in which individuals perform seasonal elevational movements. Despite its geographic and taxonomic ubiquity, there is relatively little information about the intrinsic and extrinsic factors that influence altitudinal migratory behaviour. Without this information, it is difficult to predict how rapid environmental changes will affect population viability of altitudinal migrants. To synthesize current knowledge, we compiled literature on altitudinal migration for all studied taxa, and identified the leading hypotheses explaining this behaviour. Studies of animal altitudinal migration cover many taxonomic lineages, with birds being the most commonly studied group. Altitudinal migration occurs in all continents except for Antarctica, but about a third of the literature focused on altitudinal migration in North America. Most research suggests that food and weather are the primary extrinsic drivers of altitudinal migration. In addition, substantial individual-level variation in migratory propensity exists. Individual characteristics that are associated with sex, dominance rank, and body size explain much of the variation in migratory propensity in partially migratory populations, but individual-level correlates are poorly known for most taxa. More research is needed to quantify the effects of habitat loss, habitat fragmentation, and climate change on altitudinal migrants. Demographic studies of individually marked populations would be particularly valuable for advancing knowledge of the cascading effects of environmental change on migratory propensity, movement patterns, and population viability. We conclude our review with recommendations for study designs and modelling approaches that could be used to narrow existing knowledge gaps, which currently hinder effective conservation of altitudinal migratory species.}, } @article {pmid29876997, year = {2018}, author = {Kellermann, V and Sgrò, CM}, title = {Evidence for lower plasticity in CTMAX at warmer developmental temperatures.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1300-1312}, doi = {10.1111/jeb.13303}, pmid = {29876997}, issn = {1420-9101}, support = {//Australian Research Council/ ; //Science and Industry Endowment Fund/ ; //Monash University/ ; //L'Oreal/ ; }, abstract = {Understanding the capacity for different species to reduce their susceptibility to climate change via phenotypic plasticity is essential for accurately predicting species extinction risk. The climatic variability hypothesis suggests that spatial and temporal variation in climatic variables should select for more plastic phenotypes. However, empirical support for this hypothesis is limited. Here, we examine the capacity for ten Drosophila species to increase their critical thermal maxima (CTMAX) through developmental acclimation and/or adult heat hardening. Using four fluctuating developmental temperature regimes, ranging from 13 to 33 °C, we find that most species can increase their CTMAX via developmental acclimation and adult hardening, but found no relationship between climatic variables and absolute measures of plasticity. However, when plasticity was dissected across developmental temperatures, a positive association between plasticity and one measure of climatic variability (temperature seasonality) was found when development took place between 26 and 28 °C, whereas a negative relationship was found when development took place between 20 and 23 °C. In addition, a decline in CTMAX and egg-to-adult viability, a proxy for fitness, was observed in tropical species at the warmer developmental temperatures (26-28 °C); this suggests that tropical species may be at even greater risk from climate change than currently predicted. The combined effects of developmental acclimation and adult hardening on CTMAX were small, contributing to a <0.60 °C shift in CTMAX . Although small shifts in CTMAX may increase population persistence in the shorter term, the degree to which they can contribute to meaningful responses in the long term is unclear.}, } @article {pmid29876989, year = {2018}, author = {Siepielski, AM and McPeek, SJ and McPeek, MA}, title = {Female mate preferences on high-dimensional shape variation for male species recognition traits.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1239-1250}, doi = {10.1111/jeb.13302}, pmid = {29876989}, issn = {1420-9101}, abstract = {Females in many animal species must discriminate between conspecific and heterospecific males when choosing mates. Such mating preferences that discriminate against heterospecifics may inadvertently also affect the mating success of conspecific males, particularly those with more extreme phenotypes. From this expectation, we hypothesized that female mate choice should cause Enallagma females (Odonata: Coenagrionidae) to discriminate against conspecific males with more extreme phenotypes of the claspers males use to grasp females while mating - the main feature of species mate recognition in these species. To test this, we compared cerci sizes and shapes between males that were captured while mating with females to males that were captured at the same time but not mating in three Enallagma species. In contrast to our hypothesis, we found only one of forty comparisons of shape variation that was consistent with females discriminating against males with more extreme cerci shapes. Instead, differences in cerci shape between mating and single males suggested that females displayed directional preferences on 1-4 aspects of cerci shape in two of the species in our samples. These results suggest that whereas some directional biases in mating based on cerci shape occur, the intraspecific phenotypic variation in male cerci size and shape is likely not large enough for females to express any significant incidental discrimination among conspecifics with more extreme shapes.}, } @article {pmid29876097, year = {2018}, author = {}, title = {Erratum.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5220}, doi = {10.1002/ece3.4173}, pmid = {29876097}, issn = {2045-7758}, abstract = {[This corrects the article DOI: 10.1002/ece3.684.].}, } @article {pmid29876096, year = {2018}, author = {}, title = {Erratum.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5219}, doi = {10.1002/ece3.4172}, pmid = {29876096}, issn = {2045-7758}, abstract = {[This corrects the article DOI: 10.1002/ece3.388.].}, } @article {pmid29876095, year = {2018}, author = {Woods, HA and Saudreau, M and Pincebourde, S}, title = {Structure is more important than physiology for estimating intracanopy distributions of leaf temperatures.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5206-5218}, pmid = {29876095}, issn = {2045-7758}, abstract = {Estimating leaf temperature distributions (LTDs) in canopies is crucial in forest ecology. Leaf temperature affects the exchange of heat, water, and gases, and it alters the performance of leaf-dwelling species such as arthropods, including pests and invaders. LTDs provide spatial variation that may allow arthropods to thermoregulate in the face of long-term changes in mean temperature or incidence of extreme temperatures. Yet, recording LTDs for entire canopies remains challenging. Here, we use an energy-exchange model (RATP) to examine the relative roles of climatic, structural, and physiological factors in influencing three-dimensional LTDs in tree canopies. A Morris sensitivity analysis of 13 parameters showed, not surprisingly, that climatic factors had the greatest overall effect on LTDs. In addition, however, structural parameters had greater effects on LTDs than did leaf physiological parameters. Our results suggest that it is possible to infer forest canopy LTDs from the LTDs measured or simulated just at the surface of the canopy cover over a reasonable range of parameter values. This conclusion suggests that remote sensing data can be used to estimate 3D patterns of temperature variation from 2D images of vegetation surface temperatures. Synthesis and applications. Estimating the effects of LTDs on natural plant-insect communities will require extending canopy models beyond their current focus on individual species or crops. These models, however, contain many parameters, and applying the models to new species or to mixed natural canopies depends on identifying the parameters that matter most. Our results suggest that canopy structural parameters are more important determinants of LTDs than are the physiological parameters that tend to receive the most empirical attention.}, } @article {pmid29876094, year = {2018}, author = {Boets, P and Gobeyn, S and Dillen, A and Poelman, E and Goethals, PLM}, title = {Assessing the suitable habitat for reintroduction of brown trout (Salmo trutta forma fario) in a lowland river: A modeling approach.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5191-5205}, pmid = {29876094}, issn = {2045-7758}, abstract = {Huge efforts have been made during the past decades to improve the water quality and to restore the physical habitat of rivers and streams in western Europe. This has led to an improvement in biological water quality and an increase in fish stocks in many countries. However, several rheophilic fish species such as brown trout are still categorized as vulnerable in lowland streams in Flanders (Belgium). In order to support cost-efficient restoration programs, habitat suitability modeling can be used. In this study, we developed an ensemble of habitat suitability models using metaheuristic algorithms to explore the importance of a large number of environmental variables, including chemical, physical, and hydromorphological characteristics to determine the suitable habitat for reintroduction of brown trout in the Zwalm River basin (Flanders, Belgium), which is included in the Habitats Directive. Mean stream velocity, water temperature, hiding opportunities, and presence of pools or riffles were identified as the most important variables determining the habitat suitability. Brown trout mainly preferred streams with a relatively high mean reach stream velocity (0.2-1 m/s), a low water temperature (7-15°C), and the presence of pools. The ensemble of models indicated that most of the tributaries and headwaters were suitable for the species. Synthesis and applications. Our results indicate that this modeling approach can be used to support river management, not only for brown trout but also for other species in similar geographical regions. Specifically for the Zwalm River basin, future restoration of the physical habitat, removal of the remaining migration barriers and the development of suitable spawning grounds could promote the successful restoration of brown trout.}, } @article {pmid29876093, year = {2018}, author = {O'Loughlin, LS and Green, PT}, title = {Secondary invasion un-undefined: The importance of consistent and clear terminology for classifying unique invasion phenomena.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5188-5190}, pmid = {29876093}, issn = {2045-7758}, abstract = {Linked Article: https://doi.org/10.1002/ece3.3966.}, } @article {pmid29876092, year = {2018}, author = {Pearson, DE and Ortega, YK and Runyon, J and Butler, JL}, title = {Secondary invasion re-redefined: The distinction between invader-facilitated and invader-contingent invasions as subclasses of secondary invasion.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5185-5187}, pmid = {29876092}, issn = {2045-7758}, abstract = {Linked Article: https://doi.org/10.1002/ece3.3964.}, } @article {pmid29876091, year = {2018}, author = {Fagundes, M and Weisser, W and Ganade, G}, title = {The role of nurse successional stages on species-specific facilitation in drylands: Nurse traits and facilitation skills.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5173-5184}, pmid = {29876091}, issn = {2045-7758}, abstract = {Plant establishment is a challenge in semiarid environments due to intense and frequent drought periods. The presence of neighboring trees (nurses) can increase the establishment of seedlings (targets) by improving resource availability and microclimate. The nurse effect, however, might vary depending on nurse-target species combinations but factors that predict this specificity are poorly known. We used a multispecies experiment to investigate the facilitation potential of trees from a range of successional stages, focusing on how nurse functional traits can predict species-specific interaction outcomes. We conducted a factorial field experiment in a Brazilian semiarid tropical forest during a severe drought period. Sixty pairs of interacting tree species, 20 potential nurses, and three targets were used. Seedlings of all targets were planted both under and far from the nurse canopy, in a randomized block design replicated five times. Target growth and survival were monitored for 275 days from the beginning of the dry season, and interaction outcomes were calculated using the Relative Interaction Intensity (RII) index. Nurse functional traits such as successional stage, height, wood density, and canopy diameter were used as explanatory variables to predict RII values. The average effect of nurse species on target plants was in general positive, that is, seedling survival and growth increased under the nurse canopy. However, for growth pairwise interactions were significantly species specific. Successional stage was the only functional trait explaining RII values, with pioneer tree species being stronger facilitators than later successional trees. However, the explanation power of this variable was low, and positive, negative, or neutral interactions were found among nurse trees of all successional stages. Because seedling mortality during drought in semiarid systems is high, future studies should investigate how nurse traits related to water use could influence nurse facilitation skills.}, } @article {pmid29876090, year = {2018}, author = {Clewley, GD and Robinson, RA and Clark, JA}, title = {Estimating mortality rates among passerines caught for ringing with mist nets using data from previously ringed birds.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5164-5172}, pmid = {29876090}, issn = {2045-7758}, abstract = {Mist netting is the most commonly used method for catching birds for scientific ringing, but despite decades of use, there have been few attempts to quantify the associated potential risks to the individuals caught. Any incidence of mortality through capture and handling, however low, is of potential ethical concern and may also introduce biases into the data. We estimate the mortality rate associated with capture of previously ringed (recaptured) passerines from the British and Irish Ringing Scheme (c. 1.5 million records) caught using mist nets. The importance of species, age, mass, month, time, previous captures, and an index of predator occurrence was tested using generalized linear mixed-effects models. The average mortality rate was 0.0011, most of which was reported to occur before the individuals had been extracted from the nets (c. 70% of incidents). Juveniles appeared to be at higher risk and the incidence of predation from mist nets was seasonal, with increased risk during the winter. Species differed in their reported mortality rates with the apparent risk being greatest for Chiffchaff Phylloscopus collybita (0.0029) and Bullfinch Pyrrhula pyrrhula (0.0027). To improve our understanding (and hence minimize risk in future), we recommend collecting more complete data on incidences of mortality, and also injuries; exercising increased care when the species we have identified as being at greater risk are likely to be captured, and ensuring there are robust procedures for the checking of nets (as most reported incidents of mortality occur before handling). We also recommend that all Ringing Schemes should collate and make available data on capture-related mortality. Overall rates of mortality associated with capture, although, were low and support the use of mist netting as a safe capture technique, without undue bias from mortality, when used by appropriately trained individuals.}, } @article {pmid29876089, year = {2018}, author = {Schmidt-Lebuhn, AN and Marshall, DJ and Dreis, B and Young, AG}, title = {Genetic rescue in a plant polyploid complex: Case study on the importance of genetic and trait data for conservation management.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5153-5163}, pmid = {29876089}, issn = {2045-7758}, abstract = {Knowledge of the biology of rare plant species is indispensable to aid their survival and to inform efficient conservation actions, but in many cases relevant data are lacking. In addition, while studies of conservation genetics have provided a wealth of information on the considerations arising from inbreeding, mate limitation, or local adaptation, the impact of intraspecific polyploidy remains understudied. In this study, we examined the breeding system of the rare Australian daisy Rutidosis lanata (Asteraceae) and screened ten of its populations for their ploidy level to develop recommendations for management actions, in particular, with regard to seed sourcing and genetic rescue. We found R. lanata to represent a polyploid complex, with tetraploid, pentaploid and hexaploid individuals coexisting in the same species. Crossing experiments confirmed R. lanata to be self-incompatible. Mate availability varied from c. 49% to c. 76% across populations. Most populations showed mate availability of c. 50%-70%, suggesting that mate limitation resulting from a lack of local genetic diversity may cause or at least contribute to reduced seed set. Crossing between populations resulted in significantly higher reproductive success for all populations except one, suggesting the possibility of genetic rescue through population mixing. However, the crossing experiments also showed that pentaploids suffer from a severely reduced paternal reproductive fitness. Any additional hybrids between tetraploids and pentaploids, as would be created by mixing populations with different genome copy numbers during conservation work, would consequently exacerbate mate limitation and thus reduce population viability. We conclude that seed set and thus population viability can be maximized by mixing populations with the same number of genome copies, but that populations with different numbers should be kept spatially separated. The case of Rutidosis lanata provides an example and a potential template for examining the conservation genetics of other species that may constitute polyploid complexes.}, } @article {pmid29876088, year = {2018}, author = {Huang, G and Li, CH and Li, Y}, title = {Phenological responses to nitrogen and water addition are linked to plant growth patterns in a desert herbaceous community.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5139-5152}, pmid = {29876088}, issn = {2045-7758}, abstract = {Increases in nitrogen (N) deposition and variation in precipitation have been occurring in temperate deserts; however, little information is available regarding plant phenological responses to environmental cues and their relationships with plant growth pattern in desert ecosystems. In this study, plant phenology and growth of six annuals in response to N and water addition were monitored throughout two consecutive growing seasons in 2011 and 2012 in a temperate desert in northwestern China. The effects of N and water addition on reproductive phenology differed among plant species. N and water addition consistently advanced the flowering onset time and fruiting time of four spring ephemerals; however, their effects on two spring-summer annuals were inconsistent, with advances being noted in one species and delays in another. N and water addition alone increased plant height, relative growth rate, leaf number, flower number, and individual biomass, while their combinative effects on plant growth and reproductive phenology were dependent on species. Multiple regression analysis showed that flowering onset time was negatively correlated with relative growth rate of two species, and negatively correlated with maximum plant height of the other four species. Our study demonstrates that phenological responses to increasing precipitation and N deposition varied in annuals with different life histories, whereby the effects of climate change on plant growth rate were related to reproductive phenology. Desert annuals that were able to accelerate growth rate under increasing soil resource availability tended to advance their flowering onset time to escape drought later in the growing season. This study promotes our understanding of the responses of temperate desert annuals to increasing precipitation and N deposition in this desert.}, } @article {pmid29876087, year = {2018}, author = {Salas, EAL and Valdez, R and Michel, S and Boykin, KG}, title = {Habitat assessment of Marco Polo sheep (Ovis ammon polii) in Eastern Tajikistan: Modeling the effects of climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5124-5138}, pmid = {29876087}, issn = {2045-7758}, abstract = {Identifying the factors predicting the high-elevation suitable habitats of Central Asian argali wild sheep and how these suitable habitats are affected by the changing climate regimes could help address conservation and management efforts and identify future critical habitat for the species in eastern Tajikistan. This study used environmental niche models (ENMs) to map and compare potential present and future distributions of suitable environmental conditions for Marco Polo argali. Argali occurrence points were collected during field surveys conducted from 2009 to 2016. Our models showed that terrain ruggedness and annual mean temperature had strong correlations on argali distribution. We then used two greenhouse gas concentration trajectories (RCP 4.5 and RCP 8.5) for two future time periods (2050 and 2070) to model the impacts of climate change on Marco Polo argali habitat. Results indicated a decline of suitable habitat with majority of losses observed at lower elevations (3,300-4,300 m). Models that considered all variables (climatic and nonclimatic) predicted losses of present suitable areas of 60.6% (6,928 km2) and 63.2% (7,219 km2) by 2050 and 2070, respectively. Results also showed averaged habitat gains of 46.2% (6,106 km2) at much higher elevations (4,500-6,900 m) and that elevational shifts of habitat use could occur in the future. Our results could provide information for conservation planning for this near threatened species in the region.}, } @article {pmid29876086, year = {2018}, author = {E, GX and Zhao, YJ and Chen, LP and Ma, YH and Chu, MX and Li, XL and Hong, QH and Li, LH and Guo, JJ and Zhu, L and Han, YG and Gao, HJ and Zhang, JH and Jiang, HZ and Jiang, CD and Wang, GF and Ren, HX and Jin, ML and Sun, YZ and Zhou, P and Huang, YF}, title = {Genetic diversity of the Chinese goat in the littoral zone of the Yangtze River as assessed by microsatellite and mtDNA.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5111-5123}, pmid = {29876086}, issn = {2045-7758}, abstract = {The objective of this study was to assess the genetic diversity and population structure of goats in the Yangtze River region using microsatellite and mtDNA to better understand the current status of those goat genetic diversity and the effects of natural landscape in fashion of domestic animal genetic diversity. The genetic variability of 16 goat populations in the littoral zone of the Yangtze River was estimated using 21 autosomal microsatellites, which revealed high diversity and genetic population clustering with a dispersed geographical distribution. A phylogenetic analysis of the mitochondrial D-loop region (482 bp) was conducted in 494 goats from the Yangtze River region. In total, 117 SNPs were reconstructed, and 173 haplotypes were identified, 94.5% of which belonged to lineages A and B. Lineages C, D, and G had lower frequencies (5.2%), and lineage F haplotypes were undetected. Several high-frequency haplotypes were shared by different ecogeographically distributed populations, and the close phylogenetic relationships among certain low-frequency haplotypes indicated the historical exchange of genetic material among these populations. In particular, the lineage G haplotype suggests that some west Asian goat genetic material may have been transferred to China via Muslim migration.}, } @article {pmid29876085, year = {2018}, author = {Tubay, JM and Yoshimura, J}, title = {Resistance of a terrestrial plant community to local microhabitat changes.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5101-5110}, pmid = {29876085}, issn = {2045-7758}, abstract = {The number of plant and animal species that exist today is estimated to be around 8.7 million. Approximately 300,000 of these species are flora. This extremely high species diversity has been puzzling scientist since the beginning of ecological research because most of these species compete for limited resources that should lead to the exclusion of all but few superior species. This can be seen in a number of coexistence model today that can only maintain at most four species at a time. We have shown recently that by incorporating minute differences in microhabitat to a lattice competition model, about 13 species can coexist from an initial number of 20. Here, we improve the model further by considering that microhabitat differences are not fixed but can change over time which can affect coexistence. A primary driver to this alteration is climate change, both natural and human induced. To show the resistance of a lattice plant community model, a dynamic microhabitat locality is incorporated by changing the spatial and species-specific heterogeneity of each lattice site. We show that even if the microhabitat locality of each plant species is dynamic, diversity can still be maintained in a lattice plant ecosystem model. This shows that natural communities of terrestrial plants can be resistant to the stress of microhabitat locality changes to a certain extent.}, } @article {pmid29876084, year = {2018}, author = {Goerlitz, HR}, title = {Weather conditions determine attenuation and speed of sound: Environmental limitations for monitoring and analyzing bat echolocation.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5090-5100}, pmid = {29876084}, issn = {2045-7758}, abstract = {Echolocating bats are regularly studied to investigate auditory-guided behaviors and as important bioindicators. Bioacoustic monitoring methods based on echolocation calls are increasingly used for risk assessment and to ultimately inform conservation strategies for bats. As echolocation calls transmit through the air at the speed of sound, they undergo changes due to atmospheric and geometric attenuation. Both the speed of sound and atmospheric attenuation, however, are variable and determined by weather conditions, particularly temperature and relative humidity. Changing weather conditions thus cause variation in analyzed call parameters, limiting our ability to detect, and correctly analyze bat calls. Here, I use real-world weather data to exemplify the effect of varying weather conditions on the acoustic properties of air. I then present atmospheric attenuation and speed of sound for the global range of weather conditions and bat call frequencies to show their relative effects. Atmospheric attenuation is a nonlinear function of call frequency, temperature, relative humidity, and atmospheric pressure. While atmospheric attenuation is strongly positively correlated with call frequency, it is also significantly influenced by temperature and relative humidity in a complex nonlinear fashion. Variable weather conditions thus result in variable and unknown effects on the recorded call, affecting estimates of call frequency and intensity, particularly for high frequencies. Weather-induced variation in speed of sound reaches up to about ±3%, but is generally much smaller and only relevant for acoustic localization methods of bats. The frequency- and weather-dependent variation in atmospheric attenuation has a threefold effect on bioacoustic monitoring of bats: It limits our capability (1) to monitor bats equally across time, space, and species, (2) to correctly measure frequency parameters of bat echolocation calls, particularly for high frequencies, and (3) to correctly identify bat species in species-rich assemblies or for sympatric species with similar call designs.}, } @article {pmid29876083, year = {2018}, author = {Duncanson, L and Dubayah, R}, title = {Monitoring individual tree-based change with airborne lidar.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5079-5089}, pmid = {29876083}, issn = {2045-7758}, abstract = {Understanding the carbon flux of forests is critical for constraining the global carbon cycle and managing forests to mitigate climate change. Monitoring forest growth and mortality rates is critical to this effort, but has been limited in the past, with estimates relying primarily on field surveys. Advances in remote sensing enable the potential to monitor tree growth and mortality across landscapes. This work presents an approach to measure tree growth and loss using multidate lidar campaigns in a high-biomass forest in California, USA. Individual tree crowns were delineated in 2008 and again in 2013 using a 3D crown segmentation algorithm, with derived heights and crown radii extracted and used to estimate individual tree aboveground biomass. Tree growth, loss, and aboveground biomass were analyzed with respect to tree height and crown radius. Both tree growth and loss rates decrease with increasing tree height, following the expectation that trees slow in growth rate as they age. Additionally, our aboveground biomass analysis suggests that, while the system is a net source of aboveground carbon, these carbon dynamics are governed by size class with the largest sources coming from the loss of a relatively small number of large individuals. This study demonstrates that monitoring individual tree-based growth and loss can be conducted with multidate airborne lidar, but these methods remain relatively immature. Disparities between lidar acquisitions were particularly difficult to overcome and decreased the sample of trees analyzed for growth rate in this study to 21% of the full number of delineated crowns. However, this study illuminates the potential of airborne remote sensing for ecologically meaningful forest monitoring at an individual tree level. As methods continue to improve, airborne multidate lidar will enable a richer understanding of the drivers of tree growth, loss, and aboveground carbon flux.}, } @article {pmid29876082, year = {2018}, author = {Xu, L and Lin, Q and Xu, S and Gu, Y and Hou, J and Liu, Y and Dumont, HJ and Han, BP}, title = {Daphnia diversity on the Tibetan Plateau measured by DNA taxonomy.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5069-5078}, pmid = {29876082}, issn = {2045-7758}, abstract = {Daphnia on the Tibetan Plateau has been little studied, and information on species diversity and biogeography is lacking. Here, we conducted a 4-year survey using the barcoding fragment of the mitochondrial COI gene to determine the distribution and diversity of Daphnia species found across the Plateau. Our results show that species richness is higher than previously thought, with total described and provisional species number doubling from 5 to 10. Six of the taxonomic units recovered by DNA taxonomy agreed well with morphology, but DNA barcoding distinguished three clades each for the D. longispina (D. galeata, D. dentifera, and D. longispina) and D. pulex (D. pulex, D. cf. tenebrosa, and D. pulicaria) complexes. The sequence divergence between congeneric species varied within a large range, from 9.25% to 30.71%. The endemic D. tibetana was the most common and widespread species, occurring in 12 hyposaline to mesosaline lakes. The lineage of D. longispina is the first confirmed occurrence in west Tibet.}, } @article {pmid29876081, year = {2018}, author = {Plummer, KE and Bearhop, S and Leech, DI and Chamberlain, DE and Blount, JD}, title = {Effects of winter food provisioning on the phenotypes of breeding blue tits.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5059-5068}, pmid = {29876081}, issn = {2045-7758}, abstract = {Throughout the Western World, huge numbers of people regularly supply food for wild birds. However, evidence of negative impacts of winter feeding on future reproduction has highlighted a need to improve understanding of the underlying mechanisms shaping avian responses to supplementary food. Here, we test the possibility that carry-over effects are mediated via their impact on the phenotypes of breeding birds, either by influencing the phenotypic structure of populations through changes in winter survival and/or by more direct effects on the condition of breeding birds. Using a landscape-scale 3-year study of blue tits (Cyanistes caeruleus), we demonstrate the importance of nutritional composition of supplementary food in determining carry-over effect outcomes. We show that breeding populations which had access to vitamin E-rich foods during the previous winter were comprised of individuals with reduced feather carotenoid concentrations, indicative of lower pre-feeding phenotypic condition, compared to fat-fed and unfed populations. This suggests that supplementary feeding in winter can result in altered population phenotypic structure at the time of breeding, perhaps by enhancing survival and recruitment of lower quality individuals. However, supplementation of a fat-rich diet during winter was detrimental to the oxidative state of breeding birds, with these phenotypic differences ultimately found to impact upon reproductive success. Our findings demonstrate the complex nature by which supplementary feeding can influence wild bird populations.}, } @article {pmid29876080, year = {2018}, author = {Southern, HM and Berger, MA and Young, PG and Snook, RR}, title = {Sperm morphology and the evolution of intracellular sperm-egg interactions.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5047-5058}, pmid = {29876080}, issn = {2045-7758}, abstract = {Sperm morphology is incredibly diverse, even among closely related species, yet the coevolution between males and females of fertilization recognition systems is necessary for successful karyogamy (male and female pronuclear fusion). In most species, the entire sperm enters the egg during fertilization so sperm morphological diversity may impact the intracellular sperm-egg interactions necessary for karyogamy. We quantified morphological variation of sperm inside eggs prior to and following karyogamy in several species of Drosophila to understand whether evolution of sperm morphology could influence intracellular sperm-egg interactions (ISEIs). We measured seven parameters that describe ISEIs among species to determine whether these parameters varied both within a species across development and across species at the same developmental stage. We used heterospecific crosses to test the relative role of male origin, female origin, and interaction between the male and female in determining ISEIs. We found that sperm shape changed within a species as development proceeded and, at particular development stages, species varied in some ISEIs. Parental origin had an effect on some ISEIs, with a general trend for a stronger female effect. Overall, our findings identify conserved and variable ISEIs among species and demonstrate the potential to contribute understanding to gamete evolution and development.}, } @article {pmid29876079, year = {2018}, author = {Velasquez, E and Bryan, SE and Ekins, M and Cook, AG and Hurrey, L and Firn, J}, title = {Age and area predict patterns of species richness in pumice rafts contingent on oceanic climatic zone encountered.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5034-5046}, pmid = {29876079}, issn = {2045-7758}, abstract = {The theory of island biogeography predicts that area and age explain species richness patterns (or alpha diversity) in insular habitats. Using a unique natural phenomenon, pumice rafting, we measured the influence of area, age, and oceanic climate on patterns of species richness. Pumice rafts are formed simultaneously when submarine volcanoes erupt, the pumice clasts breakup irregularly, forming irregularly shaped pumice stones which while floating through the ocean are colonized by marine biota. We analyze two eruption events and more than 5,000 pumice clasts collected from 29 sites and three climatic zones. Overall, the older and larger pumice clasts held more species. Pumice clasts arriving in tropical and subtropical climates showed this same trend, where in temperate locations species richness (alpha diversity) increased with area but decreased with age. Beta diversity analysis of the communities forming on pumice clasts that arrived in different climatic zones showed that tropical and subtropical clasts transported similar communities, while species composition on temperate clasts differed significantly from both tropical and subtropical arrivals. Using these thousands of insular habitats, we find strong evidence that area and age but also climatic conditions predict the fundamental dynamics of species richness colonizing pumice clasts.}, } @article {pmid29876078, year = {2018}, author = {Priyadarshani, N and Castro, I and Marsland, S}, title = {The impact of environmental factors in birdsong acquisition using automated recorders.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5016-5033}, pmid = {29876078}, issn = {2045-7758}, abstract = {The use of automatic acoustic recorders is becoming a principal method to survey birds in their natural habitats, as it is relatively noninvasive while still being informative. As with any other sound, birdsong degrades in amplitude, frequency, and temporal structure as it propagates to the recorder through the environment. Knowing how different birdsongs attenuate under different conditions is useful to, for example, develop protocols for deploying acoustic recorders and improve automated detection methods, an essential part of the research field that is becoming known as ecoacoustics. This article presents playback and recapture (record) experiments carried out under different environmental conditions using twenty bird calls from eleven New Zealand bird species in a native forest and an open area, answering five research questions: (1) How does birdsong attenuation differ between forest and open space? (2) What is the relationship between transmission height and birdsong attenuation? (3) How does frequency of birdsong impact the degradation of sound with distance? (4) Is birdsong attenuation different during the night compared to the day? and (5) what is the impact of wind on attenuation? Bird calls are complex sounds; therefore, we have chosen to use them rather than simple tones to ensure that this complexity is not missed in the analysis. The results demonstrate that birdsong transmission was significantly better in the forest than in the open site. During the night, the attenuation was at a minimum in both experimental sites. Transmission height affected the propagation of the songs of many species, particularly the flightless ones. The effect of wind was severe in the open site and attenuated lower frequencies. The reverberations due to reflective surfaces masked higher frequencies (8 kHz) in the forest even at moderate distances. The findings presented here can be applied to develop protocols for passive acoustic monitoring. Even though the attenuation can be generalized to frequency bands, the structure of the birdsong is also important. Selecting a reasonable sampling frequency avoids unnecessary data accumulation because higher frequencies attenuate more in the forest. Even at moderate distances, recorders capture significantly attenuated birdsong, and hence, automated analysis methods for field recordings need to be able to detect and recognize faint birdsong.}, } @article {pmid29876077, year = {2018}, author = {McGranahan, DA and Hovick, TJ and Elmore, RD and Engle, DM and Fuhlendorf, SD}, title = {Moderate patchiness optimizes heterogeneity, stability, and beta diversity in mesic grassland.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {5008-5015}, pmid = {29876077}, issn = {2045-7758}, abstract = {Heterogeneous disturbance patterns are fundamental to rangeland conservation and management because heterogeneity creates patchy vegetation, broadens niche availability, increases compositional dissimilarity, and enhances temporal stability of aboveground biomass production. Pyrodiversity is a popular concept for how variability in fire as an ecological disturbance can enhance heterogeneity, but mechanistic understanding of factors that drive heterogeneity is lacking. Mesic grasslands are examples of ecosystems in which pyrodiversity is linked strongly to broad ecological processes such as trophic interactions because grazers are attracted to recently burned areas, creating a unique ecological disturbance referred to as the fire-grazing interaction, or pyric herbivory. But several questions about the application of pyric herbivory remain: What proportion of a grazed landscape must burn, or how many patches are required, to create sufficient spatial heterogeneity and reduce temporal variability? How frequently should patches burn? Does season of fire matter? To bring theory into applied practice, we studied a gradient of grazed tallgrass prairie landscapes created by different sizes, seasons, and frequencies of fire, and used analyses sensitive to nonlinear trends. The greatest spatial heterogeneity and lowest temporal variability in aboveground plant biomass, and greatest plant functional group beta diversity, occurred in landscapes with three to four patches (25%-33% of area burned) and three- to four-year fire return intervals. Beta diversity had a positive association with spatial heterogeneity and negative relationship with temporal variability. Rather than prescribing that these results constitute best management practices, we emphasize the flexibility offered by interactions between patch number and fire frequency for matching rangeland productivity and offtake to specific management goals. As we observed no differences across season of fire, we recommend future research focus on fire frequency within a moderate proportion of the landscape burned, and consider a wider seasonal burn window.}, } @article {pmid29876076, year = {2018}, author = {Castillo, JM and Gallego-Tévar, B and Figueroa, E and Grewell, BJ and Vallet, D and Rousseau, H and Keller, J and Lima, O and Dréano, S and Salmon, A and Aïnouche, M}, title = {Low genetic diversity contrasts with high phenotypic variability in heptaploid Spartina densiflora populations invading the Pacific coast of North America.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4992-5007}, pmid = {29876076}, issn = {2045-7758}, abstract = {Species can respond to environmental pressures through genetic and epigenetic changes and through phenotypic plasticity, but few studies have evaluated the relationships between genetic differentiation and phenotypic plasticity of plant species along changing environmental conditions throughout wide latitudinal ranges. We studied inter- and intrapopulation genetic diversity (using simple sequence repeats and chloroplast DNA sequencing) and inter- and intrapopulation phenotypic variability of 33 plant traits (using field and common-garden measurements) for five populations of the invasive cordgrass Spartina densiflora Brongn. along the Pacific coast of North America from San Francisco Bay to Vancouver Island. Studied populations showed very low genetic diversity, high levels of phenotypic variability when growing in contrasted environments and high intrapopulation phenotypic variability for many plant traits. This intrapopulation phenotypic variability was especially high, irrespective of environmental conditions, for those traits showing also high phenotypic plasticity. Within-population variation represented 84% of the total genetic variation coinciding with certain individual plants keeping consistent responses for three plant traits (chlorophyll b and carotenoid contents, and dead shoot biomass) in the field and in common-garden conditions. These populations have most likely undergone genetic bottleneck since their introduction from South America; multiple introductions are unknown but possible as the population from Vancouver Island was the most recent and one of the most genetically diverse. S. densiflora appears as a species that would not be very affected itself by climate change and sea-level rise as it can disperse, establish, and acclimate to contrasted environments along wide latitudinal ranges.}, } @article {pmid29876075, year = {2018}, author = {Cantor, M and Farine, DR}, title = {Simple foraging rules in competitive environments can generate socially structured populations.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4978-4991}, pmid = {29876075}, issn = {2045-7758}, abstract = {Social vertebrates commonly form foraging groups whose members repeatedly interact with one another and are often genetically related. Many species also exhibit within-population specializations, which can range from preferences to forage in particular areas through to specializing on the type of prey they catch. However, within-population structure in foraging groups, behavioral homogeneity in foraging behavior, and relatedness could be outcomes of behavioral interactions rather than underlying drivers. We present a simple process by which grouping among foragers emerges and is maintained across generations. We introduce agent-based models to investigate (1) whether a simple rule (keep foraging with the same individuals when you were successful) leads to stable social community structure, and (2) whether this structure is robust to demographic changes and becomes kin-structured over time. We find the rapid emergence of kin-structured populations and the presence of foraging groups that control, or specialize on, a particular food resource. This pattern is strongest in small populations, mirroring empirical observations. Our results suggest that group stability can emerge as a product of network self-organization and, in doing so, may provide the necessary conditions for the evolution of more sophisticated processes, such as social learning. This taxonomically general social process has implications for our understanding of the links between population, genetic, and social structures.}, } @article {pmid29876074, year = {2018}, author = {Huang, LS and Sun, YQ and Jin, Y and Gao, Q and Hu, XG and Gao, FL and Yang, XL and Zhu, JJ and El-Kassaby, YA and Mao, JF}, title = {Development of high transferability cpSSR markers for individual identification and genetic investigation in Cupressaceae species.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4967-4977}, pmid = {29876074}, issn = {2045-7758}, abstract = {Given the low substitution rate in plastomes, the polymorphic and codominant nature of chloroplast SSRs (cpSSRs) makes them ideal markers, complementing their nuclear counterpart. In Cupressaceae, cpSSRs are mostly paternally inherited, thus, they are useful in mating systems and pollen flow studies. Using e-PCR, 92 SSR loci were identified across six Cupressaceae plastomes, and primers were designed for 26 loci with potential interspecific transferability. The 26 developed cpSSRs were polymorphic in four genera, Platycladus, Sabina, Juniperus, and Cupressus and are suitable for Cupressaceae molecular genetic studies and utilization. We genotyped 192 Platycladus orientalis samples from a core breeding population using 10 of the developed cpSSRs and 10 nuclear SSRs, and these individuals were identified with high confidence. The developed cpSSRs can be used in (1) a marker-assisted breeding scheme, specifically when paternity identification is required, (2) population genetics investigations, and (3) biogeography of Cupressaceae and unraveling the genetic relationships between related species.}, } @article {pmid29876073, year = {2018}, author = {Martin, RM and Wigand, C and Elmstrom, E and Lloret, J and Valiela, I}, title = {Long-term nutrient addition increases respiration and nitrous oxide emissions in a New England salt marsh.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4958-4966}, pmid = {29876073}, issn = {2045-7758}, abstract = {Salt marshes may act either as greenhouse gas (GHG) sources or sinks depending on hydrological conditions, vegetation communities, and nutrient availability. In recent decades, eutrophication has emerged as a major driver of change in salt marsh ecosystems. An ongoing fertilization experiment at the Great Sippewissett Marsh (Cape Cod, USA) allows for observation of the results of over four decades of nutrient addition. Here, nutrient enrichment stimulated changes to vegetation communities that, over time, have resulted in increased elevation of the marsh platform. In this study, we measured fluxes of carbon dioxide (CO 2), methane (CH 4) and nitrous oxide (N2O) in dominant vegetation zones along elevation gradients of chronically fertilized (1,572 kg N ha-1 year-1) and unfertilized (12 kg N ha-1 year-1) experimental plots at Great Sippewissett Marsh. Flux measurements were performed using darkened chambers to focus on community respiration and excluded photosynthetic CO 2 uptake. We hypothesized that N-replete conditions in fertilized plots would result in larger N2O emissions relative to control plots and that higher elevations caused by nutrient enrichment would support increased CO 2 and N2O and decreased CH 4 emissions due to the potential for more oxygen diffusion into sediment. Patterns of GHG emission supported our hypotheses. Fertilized plots were substantially larger sources of N2O and had higher community respiration rates relative to control plots, due to large emissions of these GHGs at higher elevations. While CH 4 emissions displayed a negative relationship with elevation, they were generally small across elevation gradients and nutrient enrichment treatments. Our results demonstrate that at decadal scales, vegetation community shifts and associated elevation changes driven by chronic eutrophication affect GHG emission from salt marshes. Results demonstrate the necessity of long-term fertilization experiments to understand impacts of eutrophication on ecosystem function and have implications for how chronic eutrophication may impact the role that salt marshes play in sequestering C and N.}, } @article {pmid29876072, year = {2018}, author = {Galván, I and Møller, AP}, title = {Dispersal capacity explains the evolution of lifespan variability.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4949-4957}, pmid = {29876072}, issn = {2045-7758}, abstract = {The evolutionary explanation for lifespan variation is still based on the antagonistic pleiotropy hypothesis, which has been challenged by several studies. Alternative models assume the existence of genes that favor aging and group benefits at the expense of reductions in individual lifespans. Here we propose a new model without making such assumptions. It considers that limited dispersal can generate, through reduced gene flow, spatial segregation of individual organisms according to lifespan. Individuals from subpopulations with shorter lifespan could thus resist collapse in a growing population better than individuals from subpopulations with longer lifespan, hence reducing lifespan variability within species. As species that disperse less may form more homogeneous subpopulations regarding lifespan, this may lead to a greater capacity to maximize lifespan that generates viable subpopulations, therefore creating negative associations between dispersal capacity and lifespan across species. We tested our model with individual-based simulations and a comparative study using empirical data of maximum lifespan and natal dispersal distance in 26 species of birds, controlling for the effects of genetic variability, body size, and phylogeny. Simulations resulted in maximum lifespans arising from lowest dispersal probabilities, and comparative analyses resulted in a negative association between lifespan and natal dispersal distance, thus consistent with our model. Our findings therefore suggest that the evolution of lifespan variability is the result of the ecological process of dispersal.}, } @article {pmid29876071, year = {2018}, author = {Zhang, Y and Li, J and Cheng, X and Luo, Y and Mai, Z and Zhang, S}, title = {Community differentiation of bacterioplankton in the epipelagic layer in the South China Sea.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4932-4948}, pmid = {29876071}, issn = {2045-7758}, abstract = {The South China Sea (SCS) is the largest marginal sea in the western tropical Pacific Ocean and is characterized by complex physicochemical environments. To date, the biogeographic patterns of the microbial communities have rarely been reported at a basin scale in the SCS. In this study, the bacterial assemblages inhabiting the epipelagic zone across 110°E to 119°E along 14°N latitude were uncovered. The vertical stratification of both bacterial taxa and their potential functions were revealed. These results suggest that the water depth-specific environment is a driver of the vertical bacterioplankton distribution. Moreover, the bacterial communities were different between the eastern stations and the western stations, where the environmental conditions were distinct. However, the mesoscale eddy did not show an obvious effect on the bacterial community due to the large distance between the sampling site and the center of the eddy. In addition to the water depth and longitudinal location of the samples, the heterogeneity of the phosphate and salinity concentrations also significantly contributed to the variance in the epipelagic bacterial community in the SCS. To the best of our knowledge, this study is the first to report that the variability in epipelagic bacterioplankton is driven by the physicochemical environment at the basin scale in the SCS. Our results emphasize that the ecological significance of bacterioplankton can be better understood by considering the relationship between the biogeographic distribution of bacteria and the oceanic dynamics processes.}, } @article {pmid29876070, year = {2018}, author = {Ishida, Y and Gugala, NA and Georgiadis, NJ and Roca, AL}, title = {Evolutionary and demographic processes shaping geographic patterns of genetic diversity in a keystone species, the African forest elephant (Loxodonta cyclotis).}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4919-4931}, pmid = {29876070}, issn = {2045-7758}, abstract = {The past processes that have shaped geographic patterns of genetic diversity may be difficult to infer from current patterns. However, in species with sex differences in dispersal, differing phylogeographic patterns between mitochondrial (mt) and nuclear (nu) DNA may provide contrasting insights into past events. Forest elephants (Loxodonta cyclotis) were impacted by climate and habitat change during the Pleistocene, which likely shaped phylogeographic patterns in mitochondrial (mt) DNA that have persisted due to limited female dispersal. By contrast, the nuclear (nu) DNA phylogeography of forest elephants in Central Africa has not been determined. We therefore examined the population structure of Central African forest elephants by genotyping 94 individuals from six localities at 21 microsatellite loci. Between forest elephants in western and eastern Congolian forests, there was only modest genetic differentiation, a pattern highly discordant with that of mtDNA. Nuclear genetic patterns are consistent with isolation by distance. Alternatively, male-mediated gene flow may have reduced the previous regional differentiation in Central Africa suggested by mtDNA patterns, which likely reflect forest fragmentation during the Pleistocene. In species like elephants, male-mediated gene flow erases the nuclear genetic signatures of past climate and habitat changes, but these continue to persist as patterns in mtDNA because females do not disperse. Conservation implications of these results are discussed.}, } @article {pmid29876069, year = {2018}, author = {Ratcliff, F and Bartolome, J and Macaulay, L and Spiegal, S and White, MD}, title = {Applying ecological site concepts and state-and-transition models to a grazed riparian rangeland.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4907-4918}, pmid = {29876069}, issn = {2045-7758}, abstract = {Ecological sites and state-and-transition models are useful tools for generating and testing hypotheses about drivers of vegetation composition in rangeland systems. These models have been widely implemented in upland rangelands, but comparatively, little attention has been given to developing ecological site concepts for rangeland riparian areas, and additional environmental criteria may be necessary to classify riparian ecological sites. Between 2013 and 2016, fifteen study reaches on five creeks were studied at Tejon Ranch in southern California. Data were collected to describe the relationship between riparian vegetation composition, environmental variables, and livestock management; and to explore the utility of ecological sites and state-and-transition models for describing riparian vegetation communities and for creating hypotheses about drivers of vegetation change. Hierarchical cluster analysis was used to classify the environmental and vegetation data (15 stream reaches × 4 years) into two ecological sites and eight community phases that comprised three vegetation states. Classification and regression tree (CART) analysis was used to determine the influence of abiotic site variables, annual precipitation, and cattle activity on vegetation clusters. Channel slope explained the greatest amount of variation in vegetation clusters; however, soil texture, geology, watershed size, and elevation were also selected as important predictors of vegetation composition. The classification tree built with this limited set of abiotic predictor variables explained 90% of the observed vegetation clusters. Cattle grazing and annual precipitation were not linked to qualitative differences in vegetation. Abiotic variables explained almost all of the observed riparian vegetation dynamics-and the divisions in the CART analysis corresponded roughly to the ecological sites-suggesting that ecological sites are well-suited for understanding and predicting change in this highly variable system. These findings support continued development of riparian ecological site concepts and state-and-transition models to aid decision making for conservation and management of rangeland riparian areas.}, } @article {pmid29876068, year = {2018}, author = {Zhang, L and Yun, Y and Hu, G and Peng, Y}, title = {Insights into the bacterial symbiont diversity in spiders.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4899-4906}, pmid = {29876068}, issn = {2045-7758}, abstract = {Most spiders are natural enemies of pests, and it is beneficial for the biological control of pests to learn the relationships between symbionts and their spider hosts. Research on the bacterial communities of insects has been conducted recently, but only a few studies have addressed the bacterial communities of spiders. To obtain a complete overview of the microbial communities of spiders, we examined eight species of spider (Pirata subpiraticus, Agelena difficilis, Artema atlanta, Nurscia albofasciata, Agelena labyrinthica, Ummeliata insecticeps, Dictis striatipes, and Hylyphantes graminicola) with high-throughput sequencing based on the V3 and V4 regions of the 16S rRNA gene. The bacterial communities of the spider samples were dominated by five types of endosymbionts, Wolbachia, Cardinium, Rickettsia, Spiroplasma, and Rickettsiella. The dominant OTUs (operational taxonomic units) from each of the five endosymbionts were analyzed, and the results showed that different spider species were usually dominated by special OTUs. In addition to endosymbionts, Pseudomonas, Sphingomonas, Acinetobacter, Novosphingobium, Aquabacterium, Methylobacterium, Brevundimonas, Rhizobium, Bradyrhizobium, Citrobacter, Arthrobacter, Pseudonocardia, Microbacterium, Lactobacillus, and Lactococcus were detected in spider samples in our study. Moreover, the abundance of Sphingomonas, Methylobacterium, Brevundimonas, and Rhizobium in the spider D. striatipes was significantly higher (p < .05) than the bacterial abundance of these species in seven other spider species. These findings suggest that same as in insects, co-infection of multiple types of endosymbionts is common in the hosts of the Araneae order, and other bacterial taxa also exist in spiders besides the endosymbionts.}, } @article {pmid29876067, year = {2018}, author = {Baudach, A and Lee, KZ and Vogel, H and Vilcinskas, A}, title = {Immunological larval polyphenism in the map butterfly Araschnia levana reveals the photoperiodic modulation of immunity.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4891-4898}, pmid = {29876067}, issn = {2045-7758}, abstract = {The bivoltine European map butterfly (Araschnia levana) displays seasonal polyphenism characterized by the formation of two remarkably distinct dorsal wing phenotypes: The spring generation (A. levana levana) is predominantly orange with black spots and develops from diapause pupae, whereas the summer generation (A. levana prorsa) has black, white, and orange bands and develops from subitaneous pupae. The choice between spring or summer imagoes is regulated by the photoperiod during larval and prepupal development, but polyphenism in the larvae has not been investigated before. Recently, it has been found that the prepupae of A. levana display differences in immunity-related gene expression, so we tested whether larvae destined to become spring (short-day) or summer (long-day) morphs also display differences in innate immunity. We measured larval survival following the injection of a bacterial entomopathogen (Pseudomonas entomophila), the antimicrobial activity in their hemolymph and the induced expression of selected genes encoding antimicrobial peptides (AMPs). Larvae of the short-day generation died significantly later, exhibited higher antibacterial activity in the hemolymph, and displayed higher induced expression levels of AMPs than those of the long-day generation. Our study expands the seasonal polyphenism of A. levana beyond the morphologically distinct spring and summer imagoes to include immunological larval polyphenism that reveals the photoperiodic modulation of immunity. This may reflect life-history traits that manifest as trade-offs between immunity and fecundity.}, } @article {pmid29876066, year = {2018}, author = {Nkongolo, K and Theriault, G and Michael, P}, title = {Differential levels of gene expression and molecular mechanisms between red maple (Acer rubrum) genotypes resistant and susceptible to nickel toxicity revealed by transcriptome analysis.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4876-4890}, pmid = {29876066}, issn = {2045-7758}, abstract = {Knowledge of regulation of genes associated with metal resistance in higher plants is very limited. Many plant species have developed different genetic mechanisms and metabolic pathways to cope with metal toxicity. The main objectives of this study were to 1) assess gene expression dynamics of A. rubrum in response to nickel (Ni) stress and 2) describe gene function based on ontology. Certified A. rubrum genotypes were treated with 1,600 mg of Ni per 1 Kg of soil corresponding to a soil total nickel content in a metal-contaminated region in Ontario, Canada. Nickel resistant and susceptible genotypes were selected and used for transcriptome analysis. Overall, 223,610,443 bases were generated. Trinity reads were assembled to trinity transcripts. The transcripts were mapped to protein sequences and after quality controls and appropriate trimmings, 66,783 annotated transcripts were selected as expressed among the libraries. The study reveals that nickel treatment at a high dose of 1,600 mg/kg triggers regulation of several genes. When nickel-resistant genotypes were compared to water controls, 6,263 genes were upregulated and 3,142 were downregulated. These values were 3,308 and 2,176, respectively, when susceptible genotypes were compared to water control. The coping mechanism of A. rubrum to Ni toxicity was elucidated. Upregulation of genes associated with transport in cytosol was prevalent in resistant genotypes compared to controls while upregulation of genes associated with translation in the ribosome was higher in susceptible genotypes when compared to water. The analysis revealed no major gene associated with Ni resistance in A. rubrum. Overall, the results of this study suggest that the genetic mechanism controlling the resistance of this species to nickel is controlled by genes with limited expression. The subtle differences between resistant and susceptible genotypes in gene regulation were detected using water-treated genotypes as references.}, } @article {pmid29876065, year = {2018}, author = {Ornelas-García, CP and Córdova-Tapia, F and Zambrano, L and Bermúdez-González, MP and Mercado-Silva, N and Mendoza-Garfias, B and Bautista, A}, title = {Trophic specialization and morphological divergence between two sympatric species in Lake Catemaco, Mexico.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4867-4875}, pmid = {29876065}, issn = {2045-7758}, abstract = {The association of morphological divergence with ecological segregation among closely related species could be considered as a signal of divergent selection in ecological speciation processes. Environmental signals such as diet can trigger phenotypic evolution, making polymorphic species valuable systems for studying the evolution of trophic-related traits. The main goal of this study was to analyze the association between morphological differences in trophic-related traits and ecological divergence in two sympatric species, Astyanax aeneus and A. caballeroi, inhabiting Lake Catemaco, Mexico. The trophic differences of a total of 70 individuals (35 A. aeneus and 35 A. caballeroi) were examined using stable isotopes and gut content analysis; a subset of the sample was used to characterize six trophic and six ecomorphological variables. In our results, we recovered significant differences between both species in the values of stable isotopes, with higher values of δ15N for A. caballeroi than for A. aeneus. Gut content results were consistent with the stable isotope data, with a higher proportion of invertebrates in A. caballeroi (a consumption of invertebrates ten times higher than that of A. aeneus, which in turn consumed three times more vegetal material than A. caballeroi). Finally, we found significant relationship between ecomorphology and stable isotopes (r = .24, p < .01), hence, head length, preorbital length, eye diameter, and δ15N were all positively correlated; these characteristics correspond to A. caballeroi. While longer gut and gill rakers, deeper bodies, and vegetal material consumption were positively correlated and corresponded to A. aeneus. Our results are consistent with the hypothesis that morphological divergence in trophic-related traits could be associated with niche partitioning, allowing the coexistence of closely related species and reducing interspecific competition.}, } @article {pmid29876064, year = {2018}, author = {Kim, TW and Park, S and Sin, E}, title = {At the tipping point: Differential influences of warming and deoxygenation on the survival, emergence, and respiration of cosmopolitan clams.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4860-4866}, pmid = {29876064}, issn = {2045-7758}, abstract = {Although warming and low dissolved oxygen (DO) levels are co-occurring significant climatic stressors in the ocean, the combined effects of these stressors on marine benthic animals have not been well established. Here, we tested the effects of elevated temperatures and low dissolved oxygen levels on the survival, emerging behavior from sediment, and the respiration of juvenile cosmopolitan Manila clams (Venerupis philippinarum) by exposing them to two temperatures (20 and 23.5°C) and DO levels (3.5 and 6-7 mg/L). Although within previously described tolerable ranges of temperature and DO, this 3.5°C increase in temperature combined with a 50% decrease in DO had a devastating effect on the survival of clams (85% mortality after 8 days). The mortality of clams under normoxia at 23.5°C appeared to be higher than under the low DO condition at 20°C. On the other hand, more clams emerged from sediment under the low DO condition at 20°C than under any other conditions. Oxygen consumption rates were not significantly affected by different conditions. Our results suggest temperature elevation combined with low oxygen additively increases stress on Manila clams and that warming is at least as stressful as low DO in terms of mortality. However, low DO poses another threat as it may induce emergence from sediment, and, thus increase predation risk. This is the first evidence that a combination of warming and deoxygenation stressors should reduce population survival of clams much more so than changes in a single stressor.}, } @article {pmid29876063, year = {2018}, author = {Jones, B and Shipley, E and Arnold, KE}, title = {Social immunity in honeybees-Density dependence, diet, and body mass trade-offs.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4852-4859}, pmid = {29876063}, issn = {2045-7758}, abstract = {Group living is favorable to pathogen spread due to the increased risk of disease transmission among individuals. Similar to individual immune defenses, social immunity, that is antiparasite defenses mounted for the benefit of individuals other than the actor, is predicted to be altered in social groups. The eusocial honey bee (Apis mellifera) secretes glucose oxidase (GOX), an antiseptic enzyme, throughout its colony, thereby providing immune protection to other individuals in the hive. We conducted a laboratory experiment to investigate the effects of group density on social immunity, specifically GOX activity, body mass and feeding behavior in caged honey bees. Individual honeybees caged in a low group density displayed increased GOX activity relative to those kept at a high group density. In addition, we provided evidence for a trade-off between GOX activity and body mass: Individuals caged in the low group density had a lower body mass, despite consuming more food overall. Our results provide the first experimental evidence that group density affects a social immune response in a eusocial insect. Moreover, we showed that the previously reported trade-off between immunity and body mass extends to social immunity. GOX production appears to be costly for individuals, and potentially the colony, given that low body mass is correlated with small foraging ranges in bees. At high group densities, individuals can invest less in social immunity than at low densities, while presumably gaining shared protection from infection. Thus, there is evidence that trade-offs at the individual level (GOX vs. body mass) can affect colony-level fitness.}, } @article {pmid29876062, year = {2018}, author = {Miller, CR and Latimer, CE and Zuckerberg, B}, title = {Bill size variation in northern cardinals associated with anthropogenic drivers across North America.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4841-4851}, pmid = {29876062}, issn = {2045-7758}, abstract = {Allen's rule predicts that homeotherms inhabiting cooler climates will have smaller appendages, while those inhabiting warmer climates will have larger appendages relative to body size. Birds' bills tend to be larger at lower latitudes, but few studies have tested whether modern climate change and urbanization affect bill size. Our study explored whether bill size in a wide-ranging bird would be larger in warmer, drier regions and increase with rising temperatures. Furthermore, we predicted that bill size would be larger in densely populated areas, due to urban heat island effects and the higher concentration of supplementary foods. Using measurements from 605 museum specimens, we explored the effects of climate and housing density on northern cardinal bill size over an 85-year period across the Linnaean subspecies' range. We quantified the geographic relationships between bill surface area, housing density, and minimum temperature using linear mixed effect models and geographically weighted regression. We then tested whether bill surface area changed due to housing density and temperature in three subregions (Chicago, IL., Washington, D.C., and Ithaca, NY). Across North America, cardinals occupying drier regions had larger bills, a pattern strongest in males. This relationship was mediated by temperature such that birds in warm, dry areas had larger bills than those in cool, dry areas. Over time, female cardinals' bill size increased with warming temperatures in Washington, D.C., and Ithaca. Bill size was smaller in developed areas of Chicago, but larger in Washington, D.C., while there was no pattern in Ithaca, NY. We found that climate and urbanization were strongly associated with bill size for a wide-ranging bird. These biogeographic relationships were characterized by sex-specific differences, varying relationships with housing density, and geographic variability. It is likely that anthropogenic pressures will continue to influence species, potentially promoting microevolutionary changes over space and time.}, } @article {pmid29876061, year = {2018}, author = {Yang, Y and Ni, P and Gao, Y and Xiong, W and Zhao, Y and Zhan, A}, title = {Geographical distribution of zooplankton biodiversity in highly polluted running water ecosystems: Validation of fine-scale species sorting hypothesis.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4830-4840}, pmid = {29876061}, issn = {2045-7758}, abstract = {Dispersal, rather than species sorting, is widely recognized as the dominant driver for determining meta-community structure at fine geographical scales in running water ecosystems. However, this view has been challenged by a recently proposed "fine-scale species sorting hypothesis," where community structure can be largely determined by an environmental gradient formed by local pollution at fine scales. Here, we tested this hypothesis by studying community composition and geographical distribution of metazoan zooplankton in a heavily polluted river-the North Canal River in the Haihe River Basin, China. Analysis of similarity (ANOSIM) showed that the community composition of metazoan zooplankton differed significantly (p = .001) along the environmental gradient. Ammonium (NH4-N) was the leading factor responsible for changes in zooplankton community structure and geographical distribution, followed by total dissolved solid (TDS), Na, dissolved oxygen (DO) and temperature (T). Variation partitioning revealed a larger contribution of environmental variables (21.6%) than spatial variables (1.1%) to the total explained variation of zooplankton communities. Our results support that species sorting, rather than dispersal, played a key role in structuring communities. Threshold Indicator Taxa ANalysis (TITAN) also revealed significant change points at both taxon and community levels along the gradient of NH4-N, providing further support for the influence of environmental variables on zooplankton communities. Collectively, we validate the fine-scale species sorting hypothesis when an environmental gradient exists in running water ecosystems at fine geographical scales. However, future studies on interactions between pollutants and zooplankton communities are still needed to better understand mechanisms responsible for the meta-community dynamics.}, } @article {pmid29876060, year = {2018}, author = {Evans, MJ and Rittenhouse, TAG and Hawley, JE and Rego, PW and Eggert, LS}, title = {Spatial genetic patterns indicate mechanism and consequences of large carnivore cohabitation within development.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4815-4829}, pmid = {29876060}, issn = {2045-7758}, abstract = {Patterns of human development are shifting from concentrated housing toward sprawled housing intermixed with natural land cover, and wildlife species increasingly persist in close proximity to housing, roads, and other anthropogenic features. These associations can alter population dynamics and evolutionary trajectories. Large carnivores increasingly occupy urban peripheries, yet the ecological consequences for populations established entirely within urban and exurban landscapes are largely unknown. We applied a spatial and landscape genetics approach, using noninvasively collected genetic data, to identify differences in black bear spatial genetic patterns across a rural-to-urban gradient and quantify how development affects spatial genetic processes. We quantified differences in black bear dispersal, spatial genetic structure, and migration between differing levels of development within a population primarily occupying areas with >6 houses/km2 in western Connecticut. Increased development disrupted spatial genetic structure, and we found an association between increased housing densities and longer dispersal. We also found evidence that roads limited gene flow among bears in more rural areas, yet had no effect among bears in more developed ones. These results suggest dispersal behavior is condition-dependent and indicate the potential for landscapes intermixing development and natural land cover to facilitate shifts toward increased dispersal. These changes can affect patterns of range expansion and the phenotypic and genetic composition of surrounding populations. We found evidence that subpopulations occupying more developed landscapes may be sustained by male-biased immigration, creating potentially detrimental demographic shifts.}, } @article {pmid29876059, year = {2018}, author = {Sozio, G and Curini, V and Pascucci, I and Cammà, C and Di Domenico, M}, title = {A new fast real-time PCR method for the identification of three sibling Apodemus species (A. sylvaticus, A. flavicollis, and A. alpicola) in Italy.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4807-4814}, pmid = {29876059}, issn = {2045-7758}, abstract = {The identification of field mice Apodemus flavicollis, Apodemus sylvaticus, and Apodemus alpicola represents a challenge for field scientists due to their highly overlapping morphological traits and habitats. Here, we propose a new fast real-time PCR method to discriminate the three species by species-specific TaqMan assays. Primers and probes were designed based on the alignment of 54 cyt-b partial sequences from 25 different European countries retrieved from GenBank. TaqMan assays were then tested on 133 samples from three different areas of Italy. Real-time PCR analysis showed 92 samples classified as A. flavicollis, 13 as A. sylvaticus, and 28 as A. alpicola. We did not observe any double amplification and DNA sequencing confirmed species assignment obtained by the TaqMan assays. The method is implementable on different matrices (ear tissues, tail, and blood). It can be used on dead specimens or on alive animals with minimally invasive sampling, and given the high sensitivity, the assay may be also suitable for degraded or low-DNA samples. The method proved to work well to discriminate between the species analyzed. Furthermore, it gives clear results (amplified or not) and it does not require any postamplification handling of PCR product, reducing the time needed for the analyses and the risk of carryover contamination. It therefore represents a valuable tool for field ecologists, conservationists, and epidemiologists.}, } @article {pmid29876058, year = {2018}, author = {Wellenreuther, M and Muñoz, J and Chávez-Ríos, JR and Hansson, B and Cordero-Rivera, A and Sánchez-Guillén, RA}, title = {Molecular and ecological signatures of an expanding hybrid zone.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4793-4806}, pmid = {29876058}, issn = {2045-7758}, abstract = {Many species are currently changing their distributions and subsequently form sympatric zones with hybridization between formerly allopatric species as one possible consequence. The damselfly Ischnura elegans has recently expanded south into the range of its ecologically and morphologically similar sister species Ischnura graellsii. Molecular work shows ongoing introgression between these species, but the extent to which this species mixing is modulated by ecological niche use is not known. Here, we (1) conduct a detailed population genetic analysis based on molecular markers and (2) model the ecological niche use of both species in allopatric and sympatric regions. Population genetic analyses showed chronic introgression between I. elegans and I. graellsii across a wide part of Spain, and admixture analysis corroborated this, showing that the majority of I. elegans from the sympatric zone could not be assigned to either the I. elegans or I. graellsii species cluster. Niche modeling demonstrated that I. elegans has modified its environmental niche following hybridization and genetic introgression with I. graellsii, making niche space of introgressed I. elegans populations more similar to I. graellsii. Taken together, this corroborates the view that adaptive introgression has moved genes from I. graellsii into I. elegans and that this process is enabling Spanish I. elegans to occupy a novel niche, further facilitating its expansion. Our results add to the growing evidence that hybridization can play an important and creative role in the adaptive evolution of animals.}, } @article {pmid29876057, year = {2018}, author = {Sordo, L and Santos, R and Barrote, I and Silva, J}, title = {High CO2 decreases the long-term resilience of the free-living coralline algae Phymatolithon lusitanicum.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4781-4792}, pmid = {29876057}, issn = {2045-7758}, abstract = {Mäerl/rhodolith beds are protected habitats that may be affected by ocean acidification (OA), but it is still unclear how the availability of CO 2 will affect the metabolism of these organisms. Some of the inconsistencies found among OA experimental studies may be related to experimental exposure time and synergetic effects with other stressors. Here, we investigated the long-term (up to 20 months) effects of OA on the production and calcification of the most common mäerl species of southern Portugal, Phymatolithon lusitanicum. Both the photosynthetic and calcification rates increased with CO 2 after the first 11 months of the experiment, whereas respiration slightly decreased with CO 2. After 20 months, the pattern was reversed. Acidified algae showed lower photosynthetic and calcification rates, as well as lower accumulated growth than control algae, suggesting that a metabolic threshold was exceeded. Our results indicate that long-term exposure to high CO 2 will decrease the resilience of Phymatolithon lusitanicum. Our results also show that shallow communities of these rhodoliths may be particularly at risk, while deeper rhodolith beds may become ocean acidification refuges for this biological community.}, } @article {pmid29876056, year = {2018}, author = {Davitt, G and Maute, K and Major, RE and McDonald, PG and Maron, M}, title = {Short-term response of a declining woodland bird assemblage to the removal of a despotic competitor.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4771-4780}, pmid = {29876056}, issn = {2045-7758}, abstract = {Interspecific aggression by the noisy miner (Manorina melanocephala), a highly despotic species, is homogenizing woodland avifaunas across eastern Australia. Although a native species, the noisy miner's aggressive exclusion of small birds is a Key Threatening Process under national law. Large-scale removal of noisy miners has been proposed as a management response to this threat following increases in miner presence due to anthropogenic land use practices. We tested this proposal by experimentally removing noisy miners from eucalypt woodland remnants (16-49 ha), assigned randomly as control (n = 12) or treatment (miner removal) sites (n = 12). Standardized bird surveys were conducted before and after removal, and generalized linear mixed models were used to investigate the effect of miner removal on bird assemblage metrics. Despite removing 3552 noisy miners in three sessions of systematic shooting, densities of noisy miners remained similarly high in treatment and control sites, even just 14 days after their removal. However, there was evidence of an increase in richness and abundance of small birds in treatment sites compared to controls-an effect we only expected to see if noisy miner densities were drastically reduced. We suggest that miner removal may have reduced the ability of the recolonizing miners to aggressively exclude small birds, even without substantially reducing miner densities, due to the breakdown of social structures that are central to the species' despotic behaviour. However, this effect on small birds is unlikely to persist in the long term. Synthesis and applications: Despite evidence from other studies that direct removal of noisy miners can result in rapid and sustained conservation benefit for bird communities at small scales, our findings cast doubt on the potential to scale-up this management approach. The circumstances under which direct control of noisy miners can be achieved remain unresolved.}, } @article {pmid29876055, year = {2018}, author = {Escobar, LE and Qiao, H and Cabello, J and Peterson, AT}, title = {Ecological niche modeling re-examined: A case study with the Darwin's fox.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4757-4770}, pmid = {29876055}, issn = {2045-7758}, abstract = {Many previous studies have attempted to assess ecological niche modeling performance using receiver operating characteristic (ROC) approaches, even though diverse problems with this metric have been pointed out in the literature. We explored different evaluation metrics based on independent testing data using the Darwin's Fox (Lycalopex fulvipes) as a detailed case in point. Six ecological niche models (ENMs; generalized linear models, boosted regression trees, Maxent, GARP, multivariable kernel density estimation, and NicheA) were explored and tested using six evaluation metrics (partial ROC, Akaike information criterion, omission rate, cumulative binomial probability), including two novel metrics to quantify model extrapolation versus interpolation (E-space index I) and extent of extrapolation versus Jaccard similarity (E-space index II). Different ENMs showed diverse and mixed performance, depending on the evaluation metric used. Because ENMs performed differently according to the evaluation metric employed, model selection should be based on the data available, assumptions necessary, and the particular research question. The typical ROC AUC evaluation approach should be discontinued when only presence data are available, and evaluations in environmental dimensions should be adopted as part of the toolkit of ENM researchers. Our results suggest that selecting Maxent ENM based solely on previous reports of its performance is a questionable practice. Instead, model comparisons, including diverse algorithms and parameterizations, should be the sine qua non for every study using ecological niche modeling. ENM evaluations should be developed using metrics that assess desired model characteristics instead of single measurement of fit between model and data. The metrics proposed herein that assess model performance in environmental space (i.e., E-space indices I and II) may complement current methods for ENM evaluation.}, } @article {pmid29876054, year = {2018}, author = {Donkersley, P and Rhodes, G and Pickup, RW and Jones, KC and Wilson, K}, title = {Bacterial communities associated with honeybee food stores are correlated with land use.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4743-4756}, pmid = {29876054}, issn = {2045-7758}, abstract = {Microbial communities, associated with almost all metazoans, can be inherited from the environment. Although the honeybee (Apis mellifera L.) gut microbiome is well documented, studies of the gut focus on just a small component of the bee microbiome. Other key areas such as the comb, propolis, honey, and stored pollen (bee bread) are poorly understood. Furthermore, little is known about the relationship between the pollinator microbiome and its environment. Here we present a study of the bee bread microbiome and its relationship with land use. We estimated bacterial community composition using both Illumina MiSeq DNA sequencing and denaturing gradient gel electrophoresis (DGGE). Illumina was used to gain a deeper understanding of precise species diversity across samples. DGGE was used on a larger number of samples where the costs of MiSeq had become prohibitive and therefore allowed us to study a greater number of bee breads across broader geographical axes. The former demonstrates bee bread comprises, on average, 13 distinct bacterial phyla; Bacteroidetes, Firmicutes, Alpha-proteobacteria, Beta-proteobacteria, and Gamma-proteobacteria were the five most abundant. The most common genera were Pseudomonas, Arsenophonus, Lactobacillus, Erwinia, and Acinetobacter. DGGE data show bacterial community composition and diversity varied spatially and temporally both within and between hives. Land use data were obtained from the 2007 Countryside Survey. Certain habitats, such as improved grasslands, are associated with low diversity bee breads, meaning that these environments may be poor sources of bee-associated bacteria. Decreased bee bread bacterial diversity may result in reduced function within hives. Although the dispersal of microbes is ubiquitous, this study has demonstrated landscape-level effects on microbial community composition.}, } @article {pmid29876053, year = {2018}, author = {Brustolin, MC and Nagelkerken, I and Fonseca, G}, title = {Large-scale distribution patterns of mangrove nematodes: A global meta-analysis.}, journal = {Ecology and evolution}, volume = {8}, number = {10}, pages = {4734-4742}, pmid = {29876053}, issn = {2045-7758}, abstract = {Mangroves harbor diverse invertebrate communities, suggesting that macroecological distribution patterns of habitat-forming foundation species drive the associated faunal distribution. Whether these are driven by mangrove biogeography is still ambiguous. For small-bodied taxa, local factors and landscape metrics might be as important as macroecology. We performed a meta-analysis to address the following questions: (1) can richness of mangrove trees explain macroecological patterns of nematode richness? and (2) do local landscape attributes have equal or higher importance than biogeography in structuring nematode richness? Mangrove areas of Caribbean-Southwest Atlantic, Western Indian, Central Indo-Pacific, and Southwest Pacific biogeographic regions. We used random-effects meta-analyses based on natural logarithm of the response ratio (lnRR) to assess the importance of macroecology (i.e., biogeographic regions, latitude, longitude), local factors (i.e., aboveground mangrove biomass and tree richness), and landscape metrics (forest area and shape) in structuring nematode richness from 34 mangroves sites around the world. Latitude, mangrove forest area, and forest shape index explained 19% of the heterogeneity across studies. Richness was higher at low latitudes, closer to the equator. At local scales, richness increased slightly with landscape complexity and decreased with forest shape index. Our results contrast with biogeographic diversity patterns of mangrove-associated taxa. Global-scale nematode diversity may have evolved independently of mangrove tree richness, and diversity of small-bodied metazoans is probably more closely driven by latitude and associated climates, rather than local, landscape, or global biogeographic patterns.}, } @article {pmid29875822, year = {2018}, author = {Kesäniemi, J and Boratyński, Z and Danforth, J and Itam, P and Jernfors, T and Lavrinienko, A and Mappes, T and Møller, AP and Mousseau, TA and Watts, PC}, title = {Analysis of heteroplasmy in bank voles inhabiting the Chernobyl exclusion zone: A commentary on Baker et al. (2017) "Elevated mitochondrial genome variation after 50 generations of radiation exposure in a wild rodent.".}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {820-826}, pmid = {29875822}, issn = {1752-4571}, } @article {pmid29875821, year = {2018}, author = {Gao, M and Wang, X and Yang, Y and Tabashnik, BE and Wu, Y}, title = {Epistasis confers resistance to Bt toxin Cry1Ac in the cotton bollworm.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {809-819}, pmid = {29875821}, issn = {1752-4571}, abstract = {Evolution of resistance by insect pests reduces the benefits of extensively cultivated transgenic crops that produce insecticidal proteins from Bacillus thuringiensis (Bt). Previous work showed that resistance to Bt toxin Cry1Ac, which is produced by transgenic cotton, can be conferred by mutations disrupting a cadherin protein that binds this Bt toxin in the larval midgut. However, the potential for epistatic interactions between the cadherin gene and other genes has received little attention. Here, we report evidence of epistasis conferring resistance to Cry1Ac in the cotton bollworm, Helicoverpa armigera, one of the world's most devastating crop pests. Resistance to Cry1Ac in strain LF256 originated from a field-captured male and was autosomal, recessive, and 220-fold relative to susceptible strain SCD. We conducted complementation tests for allelism by crossing LF256 with a strain in which resistance to Cry1Ac is conferred by a recessive allele at the cadherin locus HaCad. The resulting F1 offspring were resistant, suggesting that resistance to Cry1Ac in LF256 is also conferred by resistance alleles at this locus. However, the HaCad amino acid sequence in LF256 lacked insertions and deletions, and did not differ consistently between LF256 and a susceptible strain. In addition, most of the cadherin alleles in LF256 were not derived from the field-captured male. Moreover, Cry1Ac resistance was not genetically linked with the HaCad locus in LF256. Furthermore, LF256 and the susceptible strain were similar in levels of HaCad transcript, cadherin protein, and binding of Cry1Ac to cadherin. Overall, the results imply that epistasis between HaCad and an unknown second locus in LF256 yielded the observed resistance in the F1 progeny from the complementation test. The observed epistasis has important implications for interpreting results of the F1 screen used widely to monitor and analyze resistance, as well as the potential to accelerate evolution of resistance.}, } @article {pmid29875820, year = {2018}, author = {Dhole, S and Vella, MR and Lloyd, AL and Gould, F}, title = {Invasion and migration of spatially self-limiting gene drives: A comparative analysis.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {794-808}, pmid = {29875820}, issn = {1752-4571}, abstract = {Recent advances in research on gene drives have produced genetic constructs that could theoretically spread a desired gene (payload) into all populations of a species, with a single release in one place. This attribute has advantages, but also comes with risks and ethical concerns. There has been a call for research on gene drive systems that are spatially and/or temporally self-limiting. Here, we use a population genetics model to compare the expected characteristics of three spatially self-limiting gene drive systems: one-locus underdominance, two-locus underdominance and daisy-chain drives. We find large differences between these gene drives in the minimum release size required for successfully driving a payload into a population. The daisy-chain system is the most efficient, requiring the smallest release, followed by the two-locus underdominance system, and then the one-locus underdominance system. However, when the target population exchanges migrants with a nontarget population, the gene drives requiring smaller releases suffer from higher risks of unintended spread. For payloads that incur relatively low fitness costs (up to 30%), a simple daisy-chain drive is practically incapable of remaining localized, even with migration rates as low as 0.5% per generation. The two-locus underdominance system can achieve localized spread under a broader range of migration rates and of payload fitness costs, while the one-locus underdominance system largely remains localized. We also find differences in the extent of population alteration and in the permanence of the alteration achieved by the three gene drives. The two-locus underdominance system does not always spread the payload to fixation, even after successful drive, while the daisy-chain system can, for a small set of parameter values, achieve a temporally limited spread of the payload. These differences could affect the suitability of each gene drive for specific applications.}, } @article {pmid29875819, year = {2018}, author = {Sotka, EE and Baumgardner, AW and Bippus, PM and Destombe, C and Duermit, EA and Endo, H and Flanagan, BA and Kamiya, M and Lees, LE and Murren, CJ and Nakaoka, M and Shainker, SJ and Strand, AE and Terada, R and Valero, M and Weinberger, F and Krueger-Hadfield, SA}, title = {Combining niche shift and population genetic analyses predicts rapid phenotypic evolution during invasion.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {781-793}, pmid = {29875819}, issn = {1752-4571}, abstract = {The rapid evolution of non-native species can facilitate invasion success, but recent reviews indicate that such microevolution rarely yields expansion of the climatic niche in the introduced habitats. However, because some invasions originate from a geographically restricted portion of the native species range and its climatic niche, it is possible that the frequency, direction, and magnitude of phenotypic evolution during invasion have been underestimated. We explored the utility of niche shift analyses in the red seaweed Gracilaria vermiculophylla, which expanded its range from the northeastern coastline of Japan to North America, Europe, and northwestern Africa within the last 100 years. A genetically informed climatic niche shift analysis indicates that native source populations occur in colder and highly seasonal habitats, while most non-native populations typically occur in warmer, less seasonal habitats. This climatic niche expansion predicts that non-native populations evolved greater tolerance for elevated heat conditions relative to native source populations. We assayed 935 field-collected and 325 common-garden thalli from 40 locations, and as predicted, non-native populations had greater tolerance for ecologically relevant extreme heat (40°C) than did Japanese source populations. Non-native populations also had greater tolerance for cold and low-salinity stresses relative to source populations. The importance of local adaptation to warm temperatures during invasion was reinforced by evolution of parallel clines: Populations from warmer, lower-latitude estuaries had greater heat tolerance than did populations from colder, higher-latitude estuaries in both Japan and eastern North America. We conclude that rapid evolution plays an important role in facilitating the invasion success of this and perhaps other non-native marine species. Genetically informed ecological niche analyses readily generate clear predictions of phenotypic shifts during invasions and may help to resolve debate over the frequency of niche conservatism versus rapid adaptation during invasion.}, } @article {pmid29875818, year = {2018}, author = {Suffert, F and Goyeau, H and Sache, I and Carpentier, F and Gélisse, S and Morais, D and Delestre, G}, title = {Epidemiological trade-off between intra- and interannual scales in the evolution of aggressiveness in a local plant pathogen population.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {768-780}, pmid = {29875818}, issn = {1752-4571}, abstract = {The efficiency of plant resistance to fungal pathogen populations is expected to decrease over time, due to their evolution with an increase in the frequency of virulent or highly aggressive strains. This dynamics may differ depending on the scale investigated (annual or pluriannual), particularly for annual crop pathogens with both sexual and asexual reproduction cycles. We assessed this time-scale effect, by comparing aggressiveness changes in a local Zymoseptoria tritici population over an 8-month cropping season and a 6-year period of wheat monoculture. We collected two pairs of subpopulations to represent the annual and pluriannual scales: from leaf lesions at the beginning and end of a single annual epidemic and from crop debris at the beginning and end of a 6-year period. We assessed two aggressiveness traits-latent period and lesion size-on sympatric and allopatric host varieties. A trend toward decreased latent period concomitant with a significant loss of variability was established during the course of the annual epidemic, but not over the 6-year period. Furthermore, a significant cultivar effect (sympatric vs. allopatric) on the average aggressiveness of the isolates revealed host adaptation, arguing that the observed patterns could result from selection. We thus provide an experimental body of evidence of an epidemiological trade-off between the intra- and interannual scales in the evolution of aggressiveness in a local plant pathogen population. More aggressive isolates were collected from upper leaves, on which disease severity is usually lower than on the lower part of the plants left in the field as crop debris after harvest. We suggest that these isolates play little role in sexual reproduction, due to an Allee effect (difficulty finding mates at low pathogen densities), particularly as the upper parts of the plant are removed from the field, explaining the lack of transmission of increases in aggressiveness between epidemics.}, } @article {pmid29875817, year = {2018}, author = {Catalano, R and Bruckner, TA and Karasek, D and Yang, W and Shaw, GM}, title = {Reproductive suppression, birth defects, and periviable birth.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {762-767}, pmid = {29875817}, issn = {1752-4571}, abstract = {We argue that reproductive suppression has clinical implications beyond its contribution to the burden of spontaneous abortion. We theorize that the incidence of births before the 28th week of gestation, which contribute disproportionately to infant morbidity and mortality, varies over time in part due to reproductive suppression in the form of selection in utero. We further theorize that the prevalence of structural birth defects among survivors to birth from conception cohorts gauges selection in utero. We based these theories on literature positing that natural selection conserved mechanisms that spontaneously abort "risky" pregnancies including those otherwise likely to yield infants with structural birth defects or small-for-gestational age males. We test our theory using high-quality birth defect surveillance data. We identify 479,885 male infants exposed to strong selection defined as membership in conception cohorts ranked in the lowest quartile of odds of a birth defect among live-born females. We estimate the risk of periviable birth among these infants as a function of selective pressure as well as of mother's race/ethnicity and age. We find that male infants from exposed conception cohorts exhibited 10% lower odds of periviable birth than males from other conception cohorts. Our findings support the argument that selection in utero has implications beyond its contribution to the burden of spontaneous abortion.}, } @article {pmid29875816, year = {2018}, author = {Major, KM and Weston, DP and Lydy, MJ and Wellborn, GA and Poynton, HC}, title = {Unintentional exposure to terrestrial pesticides drives widespread and predictable evolution of resistance in freshwater crustaceans.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {748-761}, pmid = {29875816}, issn = {1752-4571}, abstract = {Pesticide runoff from terrestrial environments into waterways is often lethal to freshwater organisms, but exposure may also drive evolution of pesticide resistance. We analyzed the degree of resistance and molecular genetic changes underlying resistance in Hyalella azteca, a species complex of freshwater crustaceans inadvertently exposed to pesticide pollution via runoff. We surveyed 16 waterways encompassing most major watersheds throughout California and found that land use patterns are predictive of both pyrethroid presence in aquatic sediments and pyrethroid resistance in H. azteca. Nonsynonymous amino acid substitutions in the voltage-gated sodium channel including the M918L, L925I, or L925V confer resistance in H. azteca. The most frequently identified mutation, L925I, appears to be preferred within the species complex. The L925V substitution has been associated with pyrethroid resistance in another insect, but is novel in H. azteca. We documented a variety of pyrethroid resistance mutations across several species groups within this complex, indicating that pyrethroid resistance has independently arisen in H. azteca at least six separate times. Further, the high frequency of resistance alleles indicates that pesticide-mediated selection on H. azteca populations in waterways equals or exceeds that of targeted terrestrial pests. Widespread resistance throughout California suggests current practices to mitigate off-site movement of pyrethroids are inadequate to protect aquatic life from negative ecological impacts and implies the likelihood of similar findings globally.}, } @article {pmid29875815, year = {2018}, author = {Hardy, NB and Peterson, DA and Ross, L and Rosenheim, JA}, title = {Does a plant-eating insect's diet govern the evolution of insecticide resistance? Comparative tests of the pre-adaptation hypothesis.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {739-747}, pmid = {29875815}, issn = {1752-4571}, abstract = {According to the pre-adaptation hypothesis, the evolution of insecticide resistance in plant-eating insects co-opts adaptations that initially evolved during chemical warfare with their host plants. Here, we used comparative statistics to test two predictions of this hypothesis: (i) Insects with more diverse diets should evolve resistance to more diverse insecticides. (ii) Feeding on host plants with strong or diverse qualitative chemical defenses should prime an insect lineage to evolve insecticide resistance. Both predictions are supported by our tests. What makes this especially noteworthy is that differences in the diets of plant-eating insect species are typically ignored by the population genetic models we use to make predictions about insecticide resistance evolution. Those models surely capture some of the differences between host-use generalists and specialists, for example, differences in population size and migration rates into treated fields, but they miss other potentially important differences, for example, differences in metabolic diversity and gene expression plasticity. Ignoring these differences could be costly.}, } @article {pmid29875814, year = {2018}, author = {Zhou, L and Alphey, N and Walker, AS and Travers, LM and Hasan, F and Morrison, NI and Bonsall, MB and Raymond, B}, title = {Combining the high-dose/refuge strategy and self-limiting transgenic insects in resistance management-A test in experimental mesocosms.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {727-738}, pmid = {29875814}, issn = {1752-4571}, support = {BB/H01814X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The high-dose/refuge strategy has been the primary approach for resistance management in transgenic crops engineered with Bacillus thuringiensis toxins. However, there are continuing pressures from growers to reduce the size of Bt toxin-free refugia, which typically suffer higher damage from pests. One complementary approach is to release male transgenic insects with a female-specific self-limiting gene. This technology can reduce population sizes and slow the evolution of resistance by introgressing susceptible genes through males. Theory predicts that it could be used to facilitate smaller refugia or reverse the evolution of resistance. In this study, we used experimental evolution with caged insect populations to investigate the compatibility of the self-limiting system and the high-dose/refuge strategy in mitigating the evolution of resistance in diamondback moth, Plutella xylostella. The benefits of the self-limiting system were clearer at smaller refuge size, particularly when refugia were inadequate to prevent the evolution of resistance. We found that transgenic males in caged mesocosms could suppress population size and delay resistance development with 10% refugia and 4%-15% initial resistance allele frequency. Fitness costs in hemizygous transgenic insects are particularly important for introgressing susceptible alleles into target populations. Fitness costs of the self-limiting gene in this study (P. xylostella OX4139 line L) were incompletely dominant, and reduced fecundity and male mating competitiveness. The experimental evolution approach used here illustrates some of the benefits and pitfalls of combining mass release of self-limiting insects and the high-dose/refuge strategy, but does indicate that they can be complementary.}, } @article {pmid29875813, year = {2018}, author = {Puckett, EE and Micci-Smith, O and Munshi-South, J}, title = {Genomic analyses identify multiple Asian origins and deeply diverged mitochondrial clades in inbred brown rats (Rattus norvegicus).}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {718-726}, pmid = {29875813}, issn = {1752-4571}, abstract = {Over 500 strains of inbred brown rats (Rattus norvegicus) have been developed for use as a biomedical model organism. Most of these inbred lines were derived from the colony established at the Wistar Institute in 1906 or its descendants following worldwide distribution to research and breeding centers. The geographic source of the animals that founded the Wistar colony has been lost to history; thus, we compared 25 inbred rat strains to 326 wild rats from a global diversity dataset at 32 k SNPs, and 47 mitochondrial genomes to identify the source populations. We analyzed nuclear genomic data using principal component analyses and co-ancestry heat maps, and mitogenomes using phylogenetic trees and networks. In the nuclear genome, inbred rats clustered together indicating a single geographic origin for the strains studied and showed admixed ancestral variation with wild rats in eastern Asia and western North America. The Sprague Dawley derived, Wistar derived, and Brown Norway strains each had mitogenomes from different clades which diverged between 13 and 139 kya. Thus, we posit that rats originally collected for captive breeding had high mitochondrial diversity that became fixed through genetic drift and/or artificial selection. Our results show that these important medical models share common genomic ancestry from a few source populations, and opportunities exist to create new strains with diverse genomic backgrounds to provide novel insight into the genomic basis of disease phenotypes.}, } @article {pmid29875812, year = {2018}, author = {Papaïx, J and Rimbaud, L and Burdon, JJ and Zhan, J and Thrall, PH}, title = {Differential impact of landscape-scale strategies for crop cultivar deployment on disease dynamics, resistance durability and long-term evolutionary control.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {705-717}, pmid = {29875812}, issn = {1752-4571}, abstract = {A multitude of resistance deployment strategies have been proposed to tackle the evolutionary potential of pathogens to overcome plant resistance. In particular, many landscape-based strategies rely on the deployment of resistant and susceptible cultivars in an agricultural landscape as a mosaic. However, the design of such strategies is not easy as strategies targeting epidemiological or evolutionary outcomes may not be the same. Using a stochastic spatially explicit model, we studied the impact of landscape organization (as defined by the proportion of fields cultivated with a resistant cultivar and their spatial aggregation) and key pathogen life-history traits on three measures of disease control. Our results show that short-term epidemiological dynamics are optimized when landscapes are planted with a high proportion of the resistant cultivar in low aggregation. Importantly, the exact opposite situation is optimal for resistance durability. Finally, well-mixed landscapes (balanced proportions with low aggregation) are optimal for long-term evolutionary equilibrium (defined here as the level of long-term pathogen adaptation). This work offers a perspective on the potential for contrasting effects of landscape organization on different goals of disease management and highlights the role of pathogen life history.}, } @article {pmid29875811, year = {2018}, author = {Gustafson, KD and Hawkins, MG and Drazenovich, TL and Church, R and Brown, SA and Ernest, HB}, title = {Founder events, isolation, and inbreeding: Intercontinental genetic structure of the domestic ferret.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {694-704}, pmid = {29875811}, issn = {1752-4571}, abstract = {Domestication and breeding for human-desired morphological traits can reduce population genetic diversity via founder events and artificial selection, resulting in inbreeding depression and genetic disorders. The ferret (Mustela putorius furo) was domesticated from European polecats (M. putorius), transported to multiple continents, and has been artificially selected for several traits. The ferret is now a common pet, a laboratory model organism, and feral ferrets can impact native biodiversity. We hypothesized global ferret trade resulted in distinct international genetic clusters and that ferrets transported to other continents would have lower genetic diversity than ferrets from Europe because of extreme founder events and no hybridization with wild polecats or genetically diverse ferrets. To assess these hypotheses, we genotyped 765 ferrets at 31 microsatellites from 11 countries among the continents of North America, Europe, and Australia and estimated population structure and genetic diversity. Fifteen M. putorius were genotyped for comparison. Our study indicated ferrets exhibit geographically distinct clusters and highlights the low genetic variation in certain countries. Australian and North American clusters have the lowest genetic diversities and highest inbreeding metrics whereas the United Kingdom (UK) cluster exhibited intermediate genetic diversity. Non-UK European ferrets had high genetic diversity, possibly a result of introgression with wild polecats. Notably, Hungarian ferrets had the highest genetic diversity and Hungary is the only country sampled with two wild polecat species. Our research has broad social, economic, and biomedical importance. Ferret owners and veterinarians should be made aware of potential inbreeding depression. Breeders in North America and Australia would benefit by incorporating genetically diverse ferrets from mainland Europe. Laboratories using ferrets as biomedical organisms should consider diversifying their genetic stock and incorporating genetic information into bioassays. These results also have forensic applications for conserving the genetics of wild polecat species and for identifying and managing sources of feral ferrets causing ecosystem damage.}, } @article {pmid29875810, year = {2018}, author = {Christie, MR and Searle, CL}, title = {Evolutionary rescue in a host-pathogen system results in coexistence not clearance.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {681-693}, pmid = {29875810}, issn = {1752-4571}, abstract = {The evolutionary rescue of host populations may prevent extinction from novel pathogens. However, the conditions that facilitate rapid evolution of hosts, in particular the population variation in host susceptibility, and the effects of host evolution in response to pathogens on population outcomes remain largely unknown. We constructed an individual-based model to determine the relationships between genetic variation in host susceptibility and population persistence in an amphibian-fungal pathogen (Batrachochytrium dendrobatidis) system. We found that host populations can rapidly evolve reduced susceptibility to a novel pathogen and that this rapid evolution led to a 71-fold increase in the likelihood of host-pathogen coexistence. However, the increased rates of coexistence came at a cost to host populations; fewer populations cleared infection, population sizes were depressed, and neutral genetic diversity was lost. Larger adult host population sizes and greater adaptive genetic variation prior to the onset of pathogen introduction led to substantially reduced rates of extinction, suggesting that populations with these characteristics should be prioritized for conservation when species are threatened by novel infectious diseases.}, } @article {pmid29875809, year = {2018}, author = {Pilot, M and Greco, C and vonHoldt, BM and Randi, E and Jędrzejewski, W and Sidorovich, VE and Konopiński, MK and Ostrander, EA and Wayne, RK}, title = {Widespread, long-term admixture between grey wolves and domestic dogs across Eurasia and its implications for the conservation status of hybrids.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {662-680}, pmid = {29875809}, issn = {1752-4571}, abstract = {Hybridisation between a domesticated species and its wild ancestor is an important conservation problem, especially if it results in the introgression of domestic gene variants into wild species. Nevertheless, the legal status of hybrids remains unregulated, partially because of the limited understanding of the hybridisation process and its consequences. The occurrence of hybridisation between grey wolves and domestic dogs is well documented from different parts of the wolf geographic range, but little is known about the frequency of hybridisation events, their causes and the genetic impact on wolf populations. We analysed 61K SNPs spanning the canid genome in wolves from across Eurasia and North America and compared that data to similar data from dogs to identify signatures of admixture. The haplotype block analysis, which included 38 autosomes and the X chromosome, indicated the presence of individuals of mixed wolf-dog ancestry in most Eurasian wolf populations, but less admixture was present in North American populations. We found evidence for male-biased introgression of dog alleles into wolf populations, but also identified a first-generation hybrid resulting from mating between a female dog and a male wolf. We found small blocks of dog ancestry in the genomes of 62% Eurasian wolves studied and melanistic individuals with no signs of recent admixed ancestry, but with a dog-derived allele at a locus linked to melanism. Consequently, these results suggest that hybridisation has been occurring in different parts of Eurasia on multiple timescales and is not solely a recent phenomenon. Nevertheless, wolf populations have maintained genetic differentiation from dogs, suggesting that hybridisation at a low frequency does not diminish distinctiveness of the wolf gene pool. However, increased hybridisation frequency may be detrimental for wolf populations, stressing the need for genetic monitoring to assess the frequency and distribution of individuals resulting from recent admixture.}, } @article {pmid29875808, year = {2018}, author = {Jahnke, M and Jonsson, PR and Moksnes, PO and Loo, LO and Nilsson Jacobi, M and Olsen, JL}, title = {Seascape genetics and biophysical connectivity modelling support conservation of the seagrass Zostera marina in the Skagerrak-Kattegat region of the eastern North Sea.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {645-661}, pmid = {29875808}, issn = {1752-4571}, abstract = {Maintaining and enabling evolutionary processes within meta-populations are critical to resistance, resilience and adaptive potential. Knowledge about which populations act as sources or sinks, and the direction of gene flow, can help to focus conservation efforts more effectively and forecast how populations might respond to future anthropogenic and environmental pressures. As a foundation species and habitat provider, Zostera marina (eelgrass) is of critical importance to ecosystem functions including fisheries. Here, we estimate connectivity of Z. marina in the Skagerrak-Kattegat region of the North Sea based on genetic and biophysical modelling. Genetic diversity, population structure and migration were analysed at 23 locations using 20 microsatellite loci and a suite of analytical approaches. Oceanographic connectivity was analysed using Lagrangian dispersal simulations based on contemporary and historical distribution data dating back to the late 19th century. Population clusters, barriers and networks of connectivity were found to be very similar based on either genetic or oceanographic analyses. A single-generation model of dispersal was not realistic, whereas multigeneration models that integrate stepping-stone dispersal and extant and historic distribution data were able to capture and model genetic connectivity patterns well. Passive rafting of flowering shoots along oceanographic currents is the main driver of gene flow at this spatial-temporal scale, and extant genetic connectivity strongly reflects the "ghost of dispersal past" sensu Benzie, 1999. The identification of distinct clusters, connectivity hotspots and areas where connectivity has become limited over the last century is critical information for spatial management, conservation and restoration of eelgrass.}, } @article {pmid29875807, year = {2018}, author = {Brambilla, A and Keller, L and Bassano, B and Grossen, C}, title = {Heterozygosity-fitness correlation at the major histocompatibility complex despite low variation in Alpine ibex (Capra ibex).}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {631-644}, pmid = {29875807}, issn = {1752-4571}, abstract = {Crucial for the long-term survival of wild populations is their ability to fight diseases. Disease outbreaks can lead to severe population size reductions, which makes endangered and reintroduced species especially vulnerable. In vertebrates, the major histocompatibility complex (MHC) plays an important role in determining the immune response. Species that went through severe bottlenecks often show very low levels of genetic diversity at the MHC. Due to the known link between the MHC and immune response, such species are expected to be at particular risk in case of disease outbreaks. However, so far, only few studies have shown that low MHC diversity is correlated with increased disease susceptibility in species after severe bottlenecks. We investigated genetic variation at the MHC and its correlations with disease resistance and other fitness-related traits in Alpine ibex (Capra ibex), a wild goat species that underwent a strong bottleneck in the last century and that is known to have extremely low genetic variability, both genome-wide and at the MHC. We studied MHC variation in male ibex of Gran Paradiso National Park, the population used as a source for all postbottleneck reintroductions. We found that individual MHC heterozygosity (based on six microsatellites) was not correlated with genome-wide neutral heterozygosity. MHC heterozygosity, but not genome-wide heterozygosity, was positively correlated with resistance to infectious keratoconjunctivitis and with body mass. Our results show that genetic variation at the MHC plays an important role in disease resistance and, hence, should be taken into account for successfully managing species conservation.}, } @article {pmid29875806, year = {2018}, author = {Bailleul, D and Mackenzie, A and Sacchi, O and Poisson, F and Bierne, N and Arnaud-Haond, S}, title = {Large-scale genetic panmixia in the blue shark (Prionace glauca): A single worldwide population, or a genetic lag-time effect of the "grey zone" of differentiation?.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {614-630}, pmid = {29875806}, issn = {1752-4571}, abstract = {The blue shark Prionace glauca, among the most common and widely studied pelagic sharks, is a top predator, exhibiting the widest distribution range. However, little is known about its population structure and spatial dynamics. With an estimated removal of 10-20 million individuals per year by fisheries, the species is classified as "Near Threatened" by International Union for Conservation of Nature. We lack the knowledge to forecast the long-term consequences of such a huge removal on this top predator itself and on its trophic network. The genetic analysis of more than 200 samples collected at broad scale (from Mediterranean Sea, North Atlantic and Pacific Oceans) using mtDNA and nine microsatellite markers allowed to detect signatures of genetic bottlenecks but a nearly complete genetic homogeneity across the entire studied range. This apparent panmixia could be explained by a genetic lag-time effect illustrated by simulations of demographic changes that were not detectable through standard genetic analysis before a long transitional phase here introduced as the "population grey zone." The results presented here can thus encompass distinct explanatory scenarios spanning from a single demographic population to several independent populations. This limitation prevents the genetic-based delineation of stocks and thus the ability to anticipate the consequences of severe depletions at all scales. More information is required for the conservation of population(s) and management of stocks, which may be provided by large-scale sampling not only of individuals worldwide, but also of loci genomewide.}, } @article {pmid29875805, year = {2018}, author = {Perrier, C and Lozano Del Campo, A and Szulkin, M and Demeyrier, V and Gregoire, A and Charmantier, A}, title = {Great tits and the city: Distribution of genomic diversity and gene-environment associations along an urbanization gradient.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {593-613}, pmid = {29875805}, issn = {1752-4571}, support = {337365//European Research Council/International ; }, abstract = {Urbanization is a growing concern challenging the evolutionary potential of wild populations by reducing genetic diversity and imposing new selection regimes affecting many key fitness traits. However, genomic footprints of urbanization have received little attention so far. Using RAD sequencing, we investigated the genomewide effects of urbanization on neutral and adaptive genomic diversity in 140 adult great tits Parus major collected in locations with contrasted urbanization levels (from a natural forest to highly urbanized areas of a city; Montpellier, France). Heterozygosity was slightly lower in the more urbanized sites compared to the more rural ones. Low but significant effect of urbanization on genetic differentiation was found, at the site level but not at the nest level, indicative of the geographic scale of urbanization impact and of the potential for local adaptation despite gene flow. Gene-environment association tests identified numerous SNPs with small association scores to urbanization, distributed across the genome, from which a subset of 97 SNPs explained up to 81% of the variance in urbanization, overall suggesting a polygenic response to selection in the urban environment. These findings open stimulating perspectives for broader applications of high-resolution genomic tools on other cities and larger sample sizes to investigate the consistency of the effects of urbanization on the spatial distribution of genetic diversity and the polygenic nature of gene-urbanization association.}, } @article {pmid29875804, year = {2018}, author = {Létourneau, J and Ferchaud, AL and Le Luyer, J and Laporte, M and Garant, D and Bernatchez, L}, title = {Predicting the genetic impact of stocking in Brook Charr (Salvelinus fontinalis) by combining RAD sequencing and modeling of explanatory variables.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {577-592}, pmid = {29875804}, issn = {1752-4571}, abstract = {In fisheries management, intensive stocking programs are commonly used to enhance population abundance and maintain stock productivity. However, such practices are increasingly raising concerns as multiple studies documented adverse genetic and evolutionary impacts of stocking on wild populations. Improvement of stocking management relies on a better understanding of the dynamic of introgressive hybridization between wild and domestic population and on assessment of the genetic state of wild populations after stocking cessation. In Québec, Canada, over five million captive-reared Brook Charr (Salvelinus fontinalis) are stocked every year to support recreational fishing activities. Here, we investigated how variation in stocking history and environmental variables, including water temperature, pH, and dissolved oxygen, may influence the impact of stocking practices on the genetic integrity of wild Brook Charr populations. We collected DNA samples (n = 862, average of 30 individuals per lake) from 29 lakes that underwent different stocking intensity through time and also collected environmental parameters for each sampled lake. An average of 4,580 high-quality filtered SNPs was obtained for each population using genotyping by sequencing (GBS), which were then used to quantify the mean domestic membership of each sampled population. An exhaustive process of model selection was conducted to obtain a best-fitted model that explained 56% of the variance observed in mean domestic genetic membership. The number of years since the mean year of stocking was the best explanatory variable to predict variation in mean domestic genetic membership whereas environmental characteristics had little influence on observed patterns of admixture. Our model predictions also revealed that each sampled wild population could potentially return to a wild genetic state (absence of domestic genetic background) after stocking cessation. Overall, our study provides new insights on factors determining level of introgressive hybridization and suggests that stocking impacts could be reversible with time.}, } @article {pmid29875803, year = {2018}, author = {Hollins, J and Thambithurai, D and Koeck, B and Crespel, A and Bailey, DM and Cooke, SJ and Lindström, J and Parsons, KJ and Killen, SS}, title = {A physiological perspective on fisheries-induced evolution.}, journal = {Evolutionary applications}, volume = {11}, number = {5}, pages = {561-576}, pmid = {29875803}, issn = {1752-4571}, abstract = {There is increasing evidence that intense fishing pressure is not only depleting fish stocks but also causing evolutionary changes to fish populations. In particular, body size and fecundity in wild fish populations may be altered in response to the high and often size-selective mortality exerted by fisheries. While these effects can have serious consequences for the viability of fish populations, there are also a range of traits not directly related to body size which could also affect susceptibility to capture by fishing gears-and therefore fisheries-induced evolution (FIE)-but which have to date been ignored. For example, overlooked within the context of FIE is the likelihood that variation in physiological traits could make some individuals within species more vulnerable to capture. Specifically, traits related to energy balance (e.g., metabolic rate), swimming performance (e.g., aerobic scope), neuroendocrinology (e.g., stress responsiveness) and sensory physiology (e.g., visual acuity) are especially likely to influence vulnerability to capture through a variety of mechanisms. Selection on these traits could produce major shifts in the physiological traits within populations in response to fishing pressure that are yet to be considered but which could influence population resource requirements, resilience, species' distributions and responses to environmental change.}, } @article {pmid29875494, year = {2018}, author = {Guglielmi, G}, title = {Hurricanes slow their roll around the world.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {15-16}, doi = {10.1038/d41586-018-05324-5}, pmid = {29875494}, issn = {1476-4687}, mesh = {*Climate Change ; *Cyclonic Storms ; }, } @article {pmid29875493, year = {2018}, author = {Powell, K}, title = {These labs are remarkably diverse - here's why they're winning at science.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {19-22}, doi = {10.1038/d41586-018-05316-5}, pmid = {29875493}, issn = {1476-4687}, mesh = {Education, Graduate ; *Ethnic Groups ; Female ; Humans ; *Internationality ; *Laboratories ; Male ; *Minority Groups ; New Zealand ; Research/*standards ; Research Personnel/*standards ; Workforce ; }, } @article {pmid29875492, year = {2018}, author = {Gewin, V}, title = {What does it take to make an institution more diverse?.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {149-151}, doi = {10.1038/d41586-018-05317-4}, pmid = {29875492}, issn = {1476-4687}, } @article {pmid29875491, year = {2018}, author = {}, title = {Whale hunt, saltwater rice and cancer-drug boom.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {10-11}, doi = {10.1038/d41586-018-05329-0}, pmid = {29875491}, issn = {1476-4687}, } @article {pmid29875489, year = {2018}, author = {Seneviratne, SI and Rogelj, J and Séférian, R and Wartenburger, R and Allen, MR and Cain, M and Millar, RJ and Ebi, KL and Ellis, N and Hoegh-Guldberg, O and Payne, AJ and Schleussner, CF and Tschakert, P and Warren, RF}, title = {The many possible climates from the Paris Agreement's aim of 1.5 °C warming.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {41-49}, doi = {10.1038/s41586-018-0181-4}, pmid = {29875489}, issn = {1476-4687}, mesh = {*Climate ; Congresses as Topic ; Conservation of Natural Resources/trends ; Ecosystem ; Environmental Policy/*legislation & jurisprudence ; *Geographic Mapping ; Global Warming/legislation & jurisprudence/*prevention & control ; Human Activities ; *International Cooperation ; *Models, Theoretical ; Paris ; Spatio-Temporal Analysis ; Stochastic Processes ; *Temperature ; Uncertainty ; }, abstract = {The United Nations' Paris Agreement includes the aim of pursuing efforts to limit global warming to only 1.5 °C above pre-industrial levels. However, it is not clear what the resulting climate would look like across the globe and over time. Here we show that trajectories towards a '1.5 °C warmer world' may result in vastly different outcomes at regional scales, owing to variations in the pace and location of climate change and their interactions with society's mitigation, adaptation and vulnerabilities to climate change. Pursuing policies that are considered to be consistent with the 1.5 °C aim will not completely remove the risk of global temperatures being much higher or of some regional extremes reaching dangerous levels for ecosystems and societies over the coming decades.}, } @article {pmid29875488, year = {2018}, author = {Sun, BB and Maranville, JC and Peters, JE and Stacey, D and Staley, JR and Blackshaw, J and Burgess, S and Jiang, T and Paige, E and Surendran, P and Oliver-Williams, C and Kamat, MA and Prins, BP and Wilcox, SK and Zimmerman, ES and Chi, A and Bansal, N and Spain, SL and Wood, AM and Morrell, NW and Bradley, JR and Janjic, N and Roberts, DJ and Ouwehand, WH and Todd, JA and Soranzo, N and Suhre, K and Paul, DS and Fox, CS and Plenge, RM and Danesh, J and Runz, H and Butterworth, AS}, title = {Genomic atlas of the human plasma proteome.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {73-79}, doi = {10.1038/s41586-018-0175-2}, pmid = {29875488}, issn = {1476-4687}, support = {MR/L003120/1//Medical Research Council/United Kingdom ; }, mesh = {Blood Proteins/*genetics ; Female ; *Genomics ; Hepatocyte Growth Factor/genetics ; Humans ; Inflammatory Bowel Diseases/genetics ; Male ; Mutation, Missense/genetics ; Myeloblastin/genetics ; Positive Regulatory Domain I-Binding Factor 1/genetics ; Proteome/*genetics ; Proto-Oncogene Proteins/genetics ; Quantitative Trait Loci/genetics ; Vasculitis/genetics ; alpha 1-Antitrypsin/genetics ; }, abstract = {Although plasma proteins have important roles in biological processes and are the direct targets of many drugs, the genetic factors that control inter-individual variation in plasma protein levels are not well understood. Here we characterize the genetic architecture of the human plasma proteome in healthy blood donors from the INTERVAL study. We identify 1,927 genetic associations with 1,478 proteins, a fourfold increase on existing knowledge, including trans associations for 1,104 proteins. To understand the consequences of perturbations in plasma protein levels, we apply an integrated approach that links genetic variation with biological pathway, disease, and drug databases. We show that protein quantitative trait loci overlap with gene expression quantitative trait loci, as well as with disease-associated loci, and find evidence that protein biomarkers have causal roles in disease using Mendelian randomization analysis. By linking genetic factors to diseases via specific proteins, our analyses highlight potential therapeutic targets, opportunities for matching existing drugs with new disease indications, and potential safety concerns for drugs under development.}, } @article {pmid29875487, year = {2018}, author = {Ambrogio, S and Narayanan, P and Tsai, H and Shelby, RM and Boybat, I and di Nolfo, C and Sidler, S and Giordano, M and Bodini, M and Farinha, NCP and Killeen, B and Cheng, C and Jaoudi, Y and Burr, GW}, title = {Equivalent-accuracy accelerated neural-network training using analogue memory.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {60-67}, doi = {10.1038/s41586-018-0180-5}, pmid = {29875487}, issn = {1476-4687}, abstract = {Neural-network training can be slow and energy intensive, owing to the need to transfer the weight data for the network between conventional digital memory chips and processor chips. Analogue non-volatile memory can accelerate the neural-network training algorithm known as backpropagation by performing parallelized multiply-accumulate operations in the analogue domain at the location of the weight data. However, the classification accuracies of such in situ training using non-volatile-memory hardware have generally been less than those of software-based training, owing to insufficient dynamic range and excessive weight-update asymmetry. Here we demonstrate mixed hardware-software neural-network implementations that involve up to 204,900 synapses and that combine long-term storage in phase-change memory, near-linear updates of volatile capacitors and weight-data transfer with 'polarity inversion' to cancel out inherent device-to-device variations. We achieve generalization accuracies (on previously unseen data) equivalent to those of software-based training on various commonly used machine-learning test datasets (MNIST, MNIST-backrand, CIFAR-10 and CIFAR-100). The computational energy efficiency of 28,065 billion operations per second per watt and throughput per area of 3.6 trillion operations per second per square millimetre that we calculate for our implementation exceed those of today's graphical processing units by two orders of magnitude. This work provides a path towards hardware accelerators that are both fast and energy efficient, particularly on fully connected neural-network layers.}, } @article {pmid29875486, year = {2018}, author = {Mouritsen, H}, title = {Long-distance navigation and magnetoreception in migratory animals.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {50-59}, doi = {10.1038/s41586-018-0176-1}, pmid = {29875486}, issn = {1476-4687}, mesh = {Animal Migration/*physiology ; Animals ; *Cues ; Flight, Animal/physiology ; *Magnetic Fields ; Sensation/*physiology ; Spatial Navigation/*physiology ; }, abstract = {For centuries, humans have been fascinated by how migratory animals find their way over thousands of kilometres. Here, I review the mechanisms used in animal orientation and navigation with a particular focus on long-distance migrants and magnetoreception. I contend that any long-distance navigational task consists of three phases and that no single cue or mechanism will enable animals to navigate with pinpoint accuracy over thousands of kilometres. Multiscale and multisensory cue integration in the brain is needed. I conclude by raising twenty important mechanistic questions related to long-distance animal navigation that should be solved over the next twenty years.}, } @article {pmid29875485, year = {2018}, author = {Kossin, JP}, title = {A global slowdown of tropical-cyclone translation speed.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {104-107}, doi = {10.1038/s41586-018-0158-3}, pmid = {29875485}, issn = {1476-4687}, abstract = {As the Earth's atmosphere warms, the atmospheric circulation changes. These changes vary by region and time of year, but there is evidence that anthropogenic warming causes a general weakening of summertime tropical circulation1-8. Because tropical cyclones are carried along within their ambient environmental wind, there is a plausible a priori expectation that the translation speed of tropical cyclones has slowed with warming. In addition to circulation changes, anthropogenic warming causes increases in atmospheric water-vapour capacity, which are generally expected to increase precipitation rates 9 . Rain rates near the centres of tropical cyclones are also expected to increase with increasing global temperatures10-12. The amount of tropical-cyclone-related rainfall that any given local area will experience is proportional to the rain rates and inversely proportional to the translation speeds of tropical cyclones. Here I show that tropical-cyclone translation speed has decreased globally by 10 per cent over the period 1949-2016, which is very likely to have compounded, and possibly dominated, any increases in local rainfall totals that may have occurred as a result of increased tropical-cyclone rain rates. The magnitude of the slowdown varies substantially by region and by latitude, but is generally consistent with expected changes in atmospheric circulation forced by anthropogenic emissions. Of particular importance is the slowdown of 30 per cent and 20 per cent over land areas affected by western North Pacific and North Atlantic tropical cyclones, respectively, and the slowdown of 19 per cent over land areas in the Australian region. The unprecedented rainfall totals associated with the 'stall' of Hurricane Harvey13-15 over Texas in 2017 provide a notable example of the relationship between regional rainfall amounts and tropical-cyclone translation speed. Any systematic past or future change in the translation speed of tropical cyclones, particularly over land, is therefore highly relevant when considering potential changes in local rainfall totals.}, } @article {pmid29875484, year = {2018}, author = {Brown, S and Janssen, M and Adumitroaie, V and Atreya, S and Bolton, S and Gulkis, S and Ingersoll, A and Levin, S and Li, C and Li, L and Lunine, J and Misra, S and Orton, G and Steffes, P and Tabataba-Vakili, F and Kolmašová, I and Imai, M and Santolík, O and Kurth, W and Hospodarsky, G and Gurnett, D and Connerney, J}, title = {Prevalent lightning sferics at 600 megahertz near Jupiter's poles.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {87-90}, doi = {10.1038/s41586-018-0156-5}, pmid = {29875484}, issn = {1476-4687}, abstract = {Lightning has been detected on Jupiter by all visiting spacecraft through night-side optical imaging and whistler (lightning-generated radio waves) signatures1-6. Jovian lightning is thought to be generated in the mixed-phase (liquid-ice) region of convective water clouds through a charge-separation process between condensed liquid water and water-ice particles, similar to that of terrestrial (cloud-to-cloud) lightning7-9. Unlike terrestrial lightning, which emits broadly over the radio spectrum up to gigahertz frequencies10,11, lightning on Jupiter has been detected only at kilohertz frequencies, despite a search for signals in the megahertz range 12 . Strong ionospheric attenuation or a lightning discharge much slower than that on Earth have been suggested as possible explanations for this discrepancy13,14. Here we report observations of Jovian lightning sferics (broadband electromagnetic impulses) at 600 megahertz from the Microwave Radiometer 15 onboard the Juno spacecraft. These detections imply that Jovian lightning discharges are not distinct from terrestrial lightning, as previously thought. In the first eight orbits of Juno, we detected 377 lightning sferics from pole to pole. We found lightning to be prevalent in the polar regions, absent near the equator, and most frequent in the northern hemisphere, at latitudes higher than 40 degrees north. Because the distribution of lightning is a proxy for moist convective activity, which is thought to be an important source of outward energy transport from the interior of the planet16,17, increased convection towards the poles could indicate an outward internal heat flux that is preferentially weighted towards the poles9,16,18. The distribution of moist convection is important for understanding the composition, general circulation and energy transport on Jupiter.}, } @article {pmid29875414, year = {2018}, author = {Saavedra, HG and Wrabl, JO and Anderson, JA and Li, J and Hilser, VJ}, title = {Dynamic allostery can drive cold adaptation in enzymes.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {324-328}, pmid = {29875414}, issn = {1476-4687}, support = {R01 GM063747/GM/NIGMS NIH HHS/United States ; T32 GM008403/GM/NIGMS NIH HHS/United States ; }, mesh = {*Adaptation, Biological/genetics ; Adenylate Kinase/*chemistry/genetics/*metabolism ; *Allosteric Regulation/genetics ; Binding Sites/genetics ; Catalytic Domain/genetics ; *Cold Temperature ; Entropy ; Escherichia coli/*enzymology/genetics ; Models, Molecular ; Mutation ; Nuclear Magnetic Resonance, Biomolecular ; Protein Domains ; Substrate Specificity ; }, abstract = {Adaptation of organisms to environmental niches is a hallmark of evolution. One prevalent example is that of thermal adaptation, in which two descendants evolve at different temperature extremes1,2. Underlying the physiological differences between such organisms are changes in enzymes that catalyse essential reactions 3 , with orthologues from each organism undergoing adaptive mutations that preserve similar catalytic rates at their respective physiological temperatures4,5. The sequence changes responsible for these adaptive differences, however, are often at surface-exposed sites distant from the substrate-binding site, leaving the active site of the enzyme structurally unperturbed6,7. How such changes are allosterically propagated to the active site, to modulate activity, is not known. Here we show that entropy-tuning changes can be engineered into distal sites of Escherichia coli adenylate kinase, allowing us to quantitatively assess the role of dynamics in determining affinity, turnover and the role in driving adaptation. The results not only reveal a dynamics-based allosteric tuning mechanism, but also uncover a spatial separation of the control of key enzymatic parameters. Fluctuations in one mobile domain (the LID) control substrate affinity, whereas dynamic attenuation in the other domain (the AMP-binding domain) affects rate-limiting conformational changes that govern enzyme turnover. Dynamics-based regulation may thus represent an elegant, widespread and previously unrealized evolutionary adaptation mechanism that fine-tunes biological function without altering the ground state structure. Furthermore, because rigid-body conformational changes in both domains were thought to be rate limiting for turnover8,9, these adaptation studies reveal a new model for understanding the relationship between dynamics and turnover in adenylate kinase.}, } @article {pmid29875413, year = {2018}, author = {Degirmenci, B and Valenta, T and Dimitrieva, S and Hausmann, G and Basler, K}, title = {GLI1-expressing mesenchymal cells form the essential Wnt-secreting niche for colon stem cells.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {449-453}, doi = {10.1038/s41586-018-0190-3}, pmid = {29875413}, issn = {1476-4687}, mesh = {Animals ; Cell Self Renewal ; Colon/*cytology ; Female ; Intestine, Small/cytology/metabolism ; Male ; Mesenchymal Stem Cells/*cytology/*metabolism ; Mice ; Stem Cell Niche/*physiology ; Stem Cells/cytology/*metabolism ; Wnt Proteins/*metabolism ; Wnt Signaling Pathway ; Zinc Finger Protein GLI1/*metabolism ; }, abstract = {Wnt-β-catenin signalling plays a pivotal role in the homeostasis of the intestinal epithelium by promoting stem cell renewal1,2. In the small intestine, epithelial Paneth cells secrete Wnt ligands and thus adopt the function of the stem cell niche to maintain epithelial homeostasis3,4. It is unclear which cells comprise the stem cell niche in the colon. Here we show that subepithelial mesenchymal GLI1-expressing cells form this essential niche. Blocking Wnt secretion from GLI1-expressing cells prevents colonic stem cell renewal in mice: the stem cells are lost and, as a consequence, the integrity of the colonic epithelium is corrupted, leading to death. GLI1-expressing cells also play an important role in the maintenance of the small intestine, where they serve as a reserve Wnt source that becomes critical when Wnt secretion from epithelial cells is prevented. Our data suggest a mechanism by which the stem cell niche is adjusted to meet the needs of the intestine via adaptive changes in the number of mesenchymal GLI1-expressing cells.}, } @article {pmid29875412, year = {2018}, author = {Ameismeier, M and Cheng, J and Berninghausen, O and Beckmann, R}, title = {Visualizing late states of human 40S ribosomal subunit maturation.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {249-253}, doi = {10.1038/s41586-018-0193-0}, pmid = {29875412}, issn = {1476-4687}, mesh = {Base Sequence ; Cell Nucleus/metabolism ; *Cryoelectron Microscopy ; Cytoplasm/metabolism ; Humans ; Models, Molecular ; Nuclear Proteins/chemistry/metabolism/ultrastructure ; Nucleic Acid Conformation ; Protein Domains ; RNA Folding ; RNA, Ribosomal/chemistry/metabolism ; RNA-Binding Proteins/chemistry/metabolism/ultrastructure ; Ribosomal Proteins/metabolism/ultrastructure ; Ribosome Subunits, Small, Eukaryotic/chemistry/*metabolism/*ultrastructure ; }, abstract = {The formation of eukaryotic ribosomal subunits extends from the nucleolus to the cytoplasm and entails hundreds of assembly factors. Despite differences in the pathways of ribosome formation, high-resolution structural information has been available only from fungi. Here we present cryo-electron microscopy structures of late-stage human 40S assembly intermediates, representing one state reconstituted in vitro and five native states that range from nuclear to late cytoplasmic. The earliest particles reveal the position of the biogenesis factor RRP12 and distinct immature rRNA conformations that accompany the formation of the 40S subunit head. Molecular models of the late-acting assembly factors TSR1, RIOK1, RIOK2, ENP1, LTV1, PNO1 and NOB1 provide mechanistic details that underlie their contribution to a sequential 40S subunit assembly. The NOB1 architecture displays an inactive nuclease conformation that requires rearrangement of the PNO1-bound 3' rRNA, thereby coordinating the final rRNA folding steps with site 3 cleavage.}, } @article {pmid29875411, year = {2018}, author = {Marhava, P and Bassukas, AEL and Zourelidou, M and Kolb, M and Moret, B and Fastner, A and Schulze, WX and Cattaneo, P and Hammes, UZ and Schwechheimer, C and Hardtke, CS}, title = {A molecular rheostat adjusts auxin flux to promote root protophloem differentiation.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {297-300}, doi = {10.1038/s41586-018-0186-z}, pmid = {29875411}, issn = {1476-4687}, mesh = {Arabidopsis/*cytology/genetics/*metabolism ; Arabidopsis Proteins/biosynthesis/genetics/metabolism ; *Cell Differentiation ; Cell Membrane/metabolism ; Indoleacetic Acids/*metabolism ; Meristem/cytology/metabolism ; Mutation ; Phenotype ; Phloem/*cytology/metabolism ; Plant Roots/*cytology/*metabolism ; Transcription Factors/biosynthesis/genetics/metabolism ; }, abstract = {Auxin influences plant development through several distinct concentration-dependent effects 1 . In the Arabidopsis root tip, polar auxin transport by PIN-FORMED (PIN) proteins creates a local auxin accumulation that is required for the maintenance of the stem-cell niche2-4. Proximally, stem-cell daughter cells divide repeatedly before they eventually differentiate. This developmental gradient is accompanied by a gradual decrease in auxin levels as cells divide, and subsequently by a gradual increase as the cells differentiate5,6. However, the timing of differentiation is not uniform across cell files. For instance, developing protophloem sieve elements (PPSEs) differentiate as neighbouring cells still divide. Here we show that PPSE differentiation involves local steepening of the post-meristematic auxin gradient. BREVIS RADIX (BRX) and PROTEIN KINASE ASSOCIATED WITH BRX (PAX) are interacting plasma-membrane-associated, polarly localized proteins that co-localize with PIN proteins at the rootward end of developing PPSEs. Both brx and pax mutants display impaired PPSE differentiation. Similar to other AGC-family kinases, PAX activates PIN-mediated auxin efflux, whereas BRX strongly dampens this stimulation. Efficient BRX plasma-membrane localization depends on PAX, but auxin negatively regulates BRX plasma-membrane association and promotes PAX activity. Thus, our data support a model in which BRX and PAX are elements of a molecular rheostat that modulates auxin flux through developing PPSEs, thereby timing PPSE differentiation.}, } @article {pmid29875410, year = {2018}, author = {van der Linde, S and Suz, LM and Orme, CDL and Cox, F and Andreae, H and Asi, E and Atkinson, B and Benham, S and Carroll, C and Cools, N and De Vos, B and Dietrich, HP and Eichhorn, J and Gehrmann, J and Grebenc, T and Gweon, HS and Hansen, K and Jacob, F and Kristöfel, F and Lech, P and Manninger, M and Martin, J and Meesenburg, H and Merilä, P and Nicolas, M and Pavlenda, P and Rautio, P and Schaub, M and Schröck, HW and Seidling, W and Šrámek, V and Thimonier, A and Thomsen, IM and Titeux, H and Vanguelova, E and Verstraeten, A and Vesterdal, L and Waldner, P and Wijk, S and Zhang, Y and Žlindra, D and Bidartondo, MI}, title = {Environment and host as large-scale controls of ectomycorrhizal fungi.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {243-248}, doi = {10.1038/s41586-018-0189-9}, pmid = {29875410}, issn = {1476-4687}, mesh = {*Biodiversity ; Europe ; *Forests ; Fungi/*classification/isolation & purification/*physiology ; Geographic Mapping ; *Host Microbial Interactions ; Mycorrhizae/*physiology ; *Soil Microbiology ; }, abstract = {Explaining the large-scale diversity of soil organisms that drive biogeochemical processes-and their responses to environmental change-is critical. However, identifying consistent drivers of belowground diversity and abundance for some soil organisms at large spatial scales remains problematic. Here we investigate a major guild, the ectomycorrhizal fungi, across European forests at a spatial scale and resolution that is-to our knowledge-unprecedented, to explore key biotic and abiotic predictors of ectomycorrhizal diversity and to identify dominant responses and thresholds for change across complex environmental gradients. We show the effect of 38 host, environment, climate and geographical variables on ectomycorrhizal diversity, and define thresholds of community change for key variables. We quantify host specificity and reveal plasticity in functional traits involved in soil foraging across gradients. We conclude that environmental and host factors explain most of the variation in ectomycorrhizal diversity, that the environmental thresholds used as major ecosystem assessment tools need adjustment and that the importance of belowground specificity and plasticity has previously been underappreciated.}, } @article {pmid29875409, year = {2018}, author = {Que, X and Hung, MY and Yeang, C and Gonen, A and Prohaska, TA and Sun, X and Diehl, C and Määttä, A and Gaddis, DE and Bowden, K and Pattison, J and MacDonald, JG and Ylä-Herttuala, S and Mellon, PL and Hedrick, CC and Ley, K and Miller, YI and Glass, CK and Peterson, KL and Binder, CJ and Tsimikas, S and Witztum, JL}, title = {Oxidized phospholipids are proinflammatory and proatherogenic in hypercholesterolaemic mice.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {301-306}, pmid = {29875409}, issn = {1476-4687}, support = {P01 HL088093/HL/NHLBI NIH HHS/United States ; R35 HL135737/HL/NHLBI NIH HHS/United States ; P01 HL020948/HL/NHLBI NIH HHS/United States ; R01 HD082567/HD/NICHD NIH HHS/United States ; P01 HL136275/HL/NHLBI NIH HHS/United States ; P42 ES010337/ES/NIEHS NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; P30 CA023100/CA/NCI NIH HHS/United States ; R01 DK044838/DK/NIDDK NIH HHS/United States ; R01 HL119828/HL/NHLBI NIH HHS/United States ; P01 HL055798/HL/NHLBI NIH HHS/United States ; R01 HL086559/HL/NHLBI NIH HHS/United States ; P50 HD012303/HD/NICHD NIH HHS/United States ; R01 HL112276/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Aortic Valve Stenosis/drug therapy/metabolism/pathology ; Apoptosis ; Atherosclerosis/chemically induced/*drug therapy/genetics/*metabolism ; Cholesterol/administration & dosage/pharmacology ; Disease Progression ; Fatty Liver/drug therapy/metabolism/pathology ; Female ; Hypercholesterolemia/*metabolism/pathology ; Immunoglobulin M/genetics/immunology/therapeutic use ; Inflammation/drug therapy/*metabolism/pathology ; Lipoproteins, LDL/metabolism ; Macrophages, Peritoneal/metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Oxidation-Reduction ; Phospholipids/*antagonists & inhibitors/chemistry/immunology/*metabolism ; Phosphorylcholine/immunology ; Receptors, LDL/deficiency/genetics ; Single-Chain Antibodies/genetics/immunology/therapeutic use ; }, abstract = {Oxidized phospholipids (OxPL) are ubiquitous, are formed in many inflammatory tissues, including atherosclerotic lesions, and frequently mediate proinflammatory changes 1 . Because OxPL are mostly the products of non-enzymatic lipid peroxidation, mechanisms to specifically neutralize them are unavailable and their roles in vivo are largely unknown. We previously cloned the IgM natural antibody E06, which binds to the phosphocholine headgroup of OxPL, and blocks the uptake of oxidized low-density lipoprotein (OxLDL) by macrophages and inhibits the proinflammatory properties of OxPL2-4. Here, to determine the role of OxPL in vivo in the context of atherogenesis, we generated transgenic mice in the Ldlr-/- background that expressed a single-chain variable fragment of E06 (E06-scFv) using the Apoe promoter. E06-scFv was secreted into the plasma from the liver and macrophages, and achieved sufficient plasma levels to inhibit in vivo macrophage uptake of OxLDL and to prevent OxPL-induced inflammatory signalling. Compared to Ldlr-/- mice, Ldlr -/- E06-scFv mice had 57-28% less atherosclerosis after 4, 7 and even 12 months of 1% high-cholesterol diet. Echocardiographic and histologic evaluation of the aortic valves demonstrated that E06-scFv ameliorated the development of aortic valve gradients and decreased aortic valve calcification. Both cholesterol accumulation and in vivo uptake of OxLDL were decreased in peritoneal macrophages, and both peritoneal and aortic macrophages had a decreased inflammatory phenotype. Serum amyloid A was decreased by 32%, indicating decreased systemic inflammation, and hepatic steatosis and inflammation were also decreased. Finally, the E06-scFv prolonged life as measured over 15 months. Because the E06-scFv lacks the functional effects of an intact antibody other than the ability to bind OxPL and inhibit OxLDL uptake in macrophages, these data support a major proatherogenic role of OxLDL and demonstrate that OxPL are proinflammatory and proatherogenic, which E06 counteracts in vivo. These studies suggest that therapies inactivating OxPL may be beneficial for reducing generalized inflammation, including the progression of atherosclerosis, aortic stenosis and hepatic steatosis.}, } @article {pmid29875408, year = {2018}, author = {Cappell, SD and Mark, KG and Garbett, D and Pack, LR and Rape, M and Meyer, T}, title = {EMI1 switches from being a substrate to an inhibitor of APC/CCDH1 to start the cell cycle.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {313-317}, pmid = {29875408}, issn = {1476-4687}, support = {F32 GM116328/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 GM063702/GM/NIGMS NIH HHS/United States ; R01 R35GM127026/GM/NIGMS NIH HHS/United States ; R01 GM118377/GM/NIGMS NIH HHS/United States ; P50 GM107615/GM/NIGMS NIH HHS/United States ; F32 GM125246/GM/NIGMS NIH HHS/United States ; R01 GM083064/GM/NIGMS NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; F32 GM120956/GM/NIGMS NIH HHS/United States ; }, mesh = {Cdh1 Proteins/*antagonists & inhibitors/*metabolism ; Cell Cycle/*physiology ; Cell Cycle Proteins/genetics/*metabolism ; Cyclin E/metabolism ; Cyclin-Dependent Kinase 2/metabolism ; F-Box Proteins/genetics/*metabolism ; Feedback, Physiological ; G1 Phase ; HeLa Cells ; Humans ; S Phase ; }, abstract = {Mammalian cells integrate mitogen and stress signalling before the end of G1 phase to determine whether or not they enter the cell cycle1-4. Before cells can replicate their DNA in S phase, they have to activate cyclin-dependent kinases (CDKs), induce an E2F transcription program and inactivate the anaphase-promoting complex (APC/CCDH1, also known as the cyclosome), which is an E3 ubiquitin ligase that contains the co-activator CDH1 (also known as FZR, encoded by FZR1). It was recently shown that stress can return cells to quiescence after CDK2 activation and E2F induction but not after inactivation of APC/CCDH1, which suggests that APC/CCDH1 inactivation is the point of no return for cell-cycle entry 3 . Rapid inactivation of APC/CCDH1 requires early mitotic inhibitor 1 (EMI1)3,5, but the molecular mechanism that controls this cell-cycle commitment step is unknown. Here we show using human cell models that cell-cycle commitment is mediated by an EMI1-APC/CCDH1 dual-negative feedback switch, in which EMI1 is both a substrate and an inhibitor of APC/CCDH1. The inactivation switch triggers a transition between a state with low EMI1 levels and high APC/CCDH1 activity during G1 and a state with high EMI1 levels and low APC/CCDH1 activity during S and G2. Cell-based analysis, in vitro reconstitution and modelling data show that the underlying dual-negative feedback is bistable and represents a robust irreversible switch. Our study suggests that mammalian cells commit to the cell cycle by increasing CDK2 activity and EMI1 mRNA expression to trigger a one-way APC/CCDH1 inactivation switch that is mediated by EMI1 transitioning from acting as a substrate of APC/CCDH1 to being an inhibitor of APC/CCDH1.}, } @article {pmid29875407, year = {2018}, author = {Garner, MH and Li, H and Chen, Y and Su, TA and Shangguan, Z and Paley, DW and Liu, T and Ng, F and Li, H and Xiao, S and Nuckolls, C and Venkataraman, L and Solomon, GC}, title = {Comprehensive suppression of single-molecule conductance using destructive σ-interference.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {415-419}, doi = {10.1038/s41586-018-0197-9}, pmid = {29875407}, issn = {1476-4687}, abstract = {The tunnelling of electrons through molecules (and through any nanoscale insulating and dielectric material 1) shows exponential attenuation with increasing length 2 , a length dependence that is reflected in the ability of the electrons to carry an electrical current. It was recently demonstrated3-5 that coherent tunnelling through a molecular junction can also be suppressed by destructive quantum interference 6 , a mechanism that is not length-dependent. For the carbon-based molecules studied previously, cancelling all transmission channels would involve the suppression of contributions to the current from both the π-orbital and σ-orbital systems. Previous reports of destructive interference have demonstrated a decrease in transmission only through the π-channel. Here we report a saturated silicon-based molecule with a functionalized bicyclo[2.2.2]octasilane moiety that exhibits destructive quantum interference in its σ-system. Although molecular silicon typically forms conducting wires 7 , we use a combination of conductance measurements and ab initio calculations to show that destructive σ-interference, achieved here by locking the silicon-silicon bonds into eclipsed conformations within a bicyclic molecular framework, can yield extremely insulating molecules less than a nanometre in length. Our molecules also exhibit an unusually high thermopower (0.97 millivolts per kelvin), which is a further experimental signature of the suppression of all tunnelling paths by destructive interference: calculations indicate that the central bicyclo[2.2.2]octasilane unit is rendered less conductive than the empty space it occupies. The molecular design presented here provides a proof-of-concept for a quantum-interference-based approach to single-molecule insulators.}, } @article {pmid29875406, year = {2018}, author = {Hainmueller, T and Bartos, M}, title = {Parallel emergence of stable and dynamic memory engrams in the hippocampus.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {292-296}, doi = {10.1038/s41586-018-0191-2}, pmid = {29875406}, issn = {1476-4687}, mesh = {Animals ; Calcium/analysis ; Calcium Signaling ; Dentate Gyrus/cytology/physiology ; Hippocampus/*cytology/*physiology ; Mice ; Mice, Inbred C57BL ; Neurons/*physiology ; Place Cells/physiology ; Pyramidal Cells/physiology ; Spatial Memory/*physiology ; }, abstract = {During our daily life, we depend on memories of past experiences to plan future behaviour. These memories are represented by the activity of specific neuronal groups or 'engrams'1,2. Neuronal engrams are assembled during learning by synaptic modification, and engram reactivation represents the memorized experience 1 . Engrams of conscious memories are initially stored in the hippocampus for several days and then transferred to cortical areas 2 . In the dentate gyrus of the hippocampus, granule cells transform rich inputs from the entorhinal cortex into a sparse output, which is forwarded to the highly interconnected pyramidal cell network in hippocampal area CA3 3 . This process is thought to support pattern separation 4 (but see refs. 5,6). CA3 pyramidal neurons project to CA1, the hippocampal output region. Consistent with the idea of transient memory storage in the hippocampus, engrams in CA1 and CA2 do not stabilize over time7-10. Nevertheless, reactivation of engrams in the dentate gyrus can induce recall of artificial memories even after weeks 2 . Reconciliation of this apparent paradox will require recordings from dentate gyrus granule cells throughout learning, which has so far not been performed for more than a single day6,11,12. Here, we use chronic two-photon calcium imaging in head-fixed mice performing a multiple-day spatial memory task in a virtual environment to record neuronal activity in all major hippocampal subfields. Whereas pyramidal neurons in CA1-CA3 show precise and highly context-specific, but continuously changing, representations of the learned spatial sceneries in our behavioural paradigm, granule cells in the dentate gyrus have a spatial code that is stable over many days, with low place- or context-specificity. Our results suggest that synaptic weights along the hippocampal trisynaptic loop are constantly reassigned to support the formation of dynamic representations in downstream hippocampal areas based on a stable code provided by the dentate gyrus.}, } @article {pmid29875405, year = {2018}, author = {Gröbner, SN and Worst, BC and Weischenfeldt, J and Buchhalter, I and Kleinheinz, K and Rudneva, VA and Johann, PD and Balasubramanian, GP and Segura-Wang, M and Brabetz, S and Bender, S and Hutter, B and Sturm, D and Pfaff, E and Hübschmann, D and Zipprich, G and Heinold, M and Eils, J and Lawerenz, C and Erkek, S and Lambo, S and Waszak, S and Blattmann, C and Borkhardt, A and Kuhlen, M and Eggert, A and Fulda, S and Gessler, M and Wegert, J and Kappler, R and Baumhoer, D and Burdach, S and Kirschner-Schwabe, R and Kontny, U and Kulozik, AE and Lohmann, D and Hettmer, S and Eckert, C and Bielack, S and Nathrath, M and Niemeyer, C and Richter, GH and Schulte, J and Siebert, R and Westermann, F and Molenaar, JJ and Vassal, G and Witt, H and Burkhardt, B and Kratz, CP and Witt, O and van Tilburg, CM and Kramm, CM and Fleischhack, G and Dirksen, U and Rutkowski, S and Frühwald, M and von Hoff, K and Wolf, S and Klingebiel, T and Koscielniak, E and Landgraf, P and Koster, J and Resnick, AC and Zhang, J and Liu, Y and Zhou, X and Waanders, AJ and Zwijnenburg, DA and Raman, P and Brors, B and Weber, UD and Northcott, PA and Pajtler, KW and Kool, M and Piro, RM and Korbel, JO and Schlesner, M and Eils, R and Jones, DTW and Lichter, P and Chavez, L and Zapatka, M and Pfister, SM and , and , }, title = {Author Correction: The landscape of genomic alterations across childhood cancers.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {E10}, doi = {10.1038/s41586-018-0167-2}, pmid = {29875405}, issn = {1476-4687}, abstract = {In this Article, author Benedikt Brors was erroneously associated with affiliation number '8' (Department of Developmental Neurobiology, St Jude Children's Research Hospital, Memphis, Tennessee, USA); the author's two other affiliations (affiliations '3' and '7', both at the German Cancer Research Center (DKFZ)) were correct. This has been corrected online.}, } @article {pmid29875404, year = {2018}, author = {Crowther, TW and Machmuller, MB and Carey, JC and Allison, SD and Blair, JM and Bridgham, SD and Burton, AJ and Dijkstra, FA and Elberling, B and Estiarte, M and Larsen, KS and Laudon, H and Lupascu, M and Marhan, S and Mohan, J and Niu, S and Peñuelas, JJ and Schmidt, IK and Templer, PH and Kröel-Dulay, G and Frey, S and Bradford, MA}, title = {Author Correction: Crowther et al. reply.}, journal = {Nature}, volume = {560}, number = {7716}, pages = {E1}, doi = {10.1038/s41586-018-0192-1}, pmid = {29875404}, issn = {1476-4687}, abstract = {In this Brief Communications Arising Reply, the affiliation for author P. H. Templer was incorrectly listed as 'Department of Ecology & Evolutionary Biology, University of California Irvine, Irvine, California 92697, USA' instead of 'Department of Biology, Boston University, Boston, Massachusetts 02215, USA'. This has been corrected online.}, } @article {pmid29875142, year = {2018}, author = {Fan, PD and Narzisi, G and Jayaprakash, AD and Venturini, E and Robine, N and Smibert, P and Germer, S and Yu, HA and Jordan, EJ and Paik, PK and Janjigian, YY and Chaft, JE and Wang, L and Jungbluth, AA and Middha, S and Spraggon, L and Qiao, H and Lovly, CM and Kris, MG and Riely, GJ and Politi, K and Varmus, H and Ladanyi, M}, title = {YES1 amplification is a mechanism of acquired resistance to EGFR inhibitors identified by transposon mutagenesis and clinical genomics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {E6030-E6038}, pmid = {29875142}, issn = {1091-6490}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA121210/CA/NCI NIH HHS/United States ; R01 CA120247/CA/NCI NIH HHS/United States ; P01 CA129243/CA/NCI NIH HHS/United States ; P50 CA196530/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; *DNA Transposable Elements ; *Drug Resistance, Neoplasm ; Enzyme Inhibitors/*pharmacology ; *ErbB Receptors/antagonists & inhibitors/genetics/metabolism ; *Gene Amplification ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; *Lung Neoplasms/drug therapy/genetics/metabolism/pathology ; Proto-Oncogene Proteins c-fyn/genetics/metabolism ; *Proto-Oncogene Proteins c-yes/biosynthesis/genetics ; Proto-Oncogene Proteins pp60(c-src)/genetics/metabolism ; }, abstract = {In ∼30% of patients with EGFR-mutant lung adenocarcinomas whose disease progresses on EGFR inhibitors, the basis for acquired resistance remains unclear. We have integrated transposon mutagenesis screening in an EGFR-mutant cell line and clinical genomic sequencing in cases of acquired resistance to identify mechanisms of resistance to EGFR inhibitors. The most prominent candidate genes identified by insertions in or near the genes during the screen were MET, a gene whose amplification is known to mediate resistance to EGFR inhibitors, and the gene encoding the Src family kinase YES1. Cell clones with transposon insertions that activated expression of YES1 exhibited resistance to all three generations of EGFR inhibitors and sensitivity to pharmacologic and siRNA-mediated inhibition of YES1 Analysis of clinical genomic sequencing data from cases of acquired resistance to EGFR inhibitors revealed amplification of YES1 in five cases, four of which lacked any other known mechanisms of resistance. Preinhibitor samples, available for two of the five patients, lacked YES1 amplification. None of 136 postinhibitor samples had detectable amplification of other Src family kinases (SRC and FYN). YES1 amplification was also found in 2 of 17 samples from ALK fusion-positive lung cancer patients who had progressed on ALK TKIs. Taken together, our findings identify acquired amplification of YES1 as a recurrent and targetable mechanism of resistance to EGFR inhibition in EGFR-mutant lung cancers and demonstrate the utility of transposon mutagenesis in discovering clinically relevant mechanisms of drug resistance.}, } @article {pmid29875141, year = {2018}, author = {Schleiss, MR}, title = {Recombinant cytomegalovirus glycoprotein B vaccine: Rethinking the immunological basis of protection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6110-6112}, pmid = {29875141}, issn = {1091-6490}, support = {R01 HD079918/HD/NICHD NIH HHS/United States ; }, mesh = {Antibodies, Viral ; Cytomegalovirus/immunology ; Cytomegalovirus Infections ; *Cytomegalovirus Vaccines ; *Viral Envelope Proteins ; }, } @article {pmid29874652, year = {2018}, author = {Razak, KA}, title = {Adaptations for Substrate Gleaning in Bats: The Pallid Bat as a Case Study.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {2}, pages = {97-108}, doi = {10.1159/000488873}, pmid = {29874652}, issn = {1421-9743}, abstract = {Substrate gleaning is a foraging strategy in which bats use a mixture of echolocation, prey-generated sounds, and vision to localize and hunt surface-dwelling prey. Many substrate-gleaning species depend primarily on prey-generated noise to hunt. Use of echolocation is limited to general orientation and obstacle avoidance. This foraging strategy involves a different set of selective pressures on morphology, behavior, and auditory system organization of bats compared to the use of echolocation for both hunting and navigation. Gleaning likely evolved to hunt in cluttered environments and/or as a counterstrategy to reduce detection by eared prey. Gleaning bats simultaneously receive streams of echoes from obstacles and prey-generated noise, and have to segregate these acoustic streams to attend to one or both. Not only do these bats have to be exquisitely sensitive to the soft, low frequency sounds produced by walking/rustling prey, they also have to precisely localize these sounds. Gleaners typically use low intensity echolocation calls. Such stealth echolocation requires a nervous system that is attuned to low intensity sound processing. In addition, landing on the ground to hunt may bring gleaners in close proximity to venomous prey. In fact, at least 2 gleaning bat species are known to hunt highly venomous scorpions. While a number of studies have addressed adaptations for echolocation in bats that hunt in the air, very little is known about the morphological, behavioral, and neural specializations for gleaning in bats. This review highlights the novel insights gleaning bats provide into bat evolution, particularly auditory pathway organization and ion channel structure/function relationships. Gleaning bats are found in multiple families, suggesting convergent evolution of specializations for gleaning as a foraging strategy. However, most of this review is based on recent work on a single species - the pallid bat (Antrozous palli dus) - symptomatic of the fact that more comparative work is needed to identify the mechanisms that facilitate gleaning behavior.}, } @article {pmid29874390, year = {2018}, author = {Redi, D and Raffaelli, CS and Rossetti, B and De Luca, A and Montagnani, F}, title = {Staphylococcus aureus vaccine preclinical and clinical development: current state of the art.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {208-213}, pmid = {29874390}, issn = {1121-7138}, mesh = {Clinical Trials as Topic ; Drug Evaluation, Preclinical ; Humans ; Staphylococcal Infections/microbiology/*prevention & control ; Staphylococcal Vaccines/*immunology ; *Staphylococcus aureus ; }, abstract = {Staphylococcus aureus is a major pathogen in both community and hospital settings. It is a significant etiological agent to treat in healthcare-related infections due to both its ability to cause invasive infection as well as to form biofilm on biomaterials and the high prevalence of resistance to first line antibiotics. The most challenging preventive strategy is vaccine development to guarantee a full and durable protection from staphylococcal diseases in all different high-risk populations, even if the lack of a known correlate of protection from S. aureus is a major hindrance to this effort. We aimed to review the most recent advances in the field of vaccinology against S. aureus, highlighting the potential for future application of the different experimental vaccine types. Several vaccines have completed their preclinical phase of development and others have been tested in humans, however no successful phase III clinical trial has yet been completed.}, } @article {pmid29874389, year = {2018}, author = {Murina, F and Vicariotto, F and Di Francesco, S}, title = {Thymol, eugenol and lactobacilli in a medical device for the treatment of bacterial vaginosis and vulvovaginal candidiasis.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {220-224}, pmid = {29874389}, issn = {1121-7138}, mesh = {Administration, Intravaginal ; Adult ; Candidiasis, Vulvovaginal/*drug therapy ; Drug Combinations ; Eugenol/administration & dosage/*therapeutic use ; Female ; Humans ; *Lactobacillus fermentum ; *Lactobacillus plantarum ; Middle Aged ; Thymol/administration & dosage/*therapeutic use ; Vagina/microbiology ; Vaginosis, Bacterial/*drug therapy ; }, abstract = {The aim of this non-interventional, observational, multicentre, open-label study was to assess the effectiveness of a vaginal gel containing extracts of Thymus vulgaris and Eugenia caryophyllus in conjunction with two specific lactobacilli strains (Lactobacillus fermentum LF10 and Lactobacillus plantarum LP02) specifically formulated in slow-release vaginal capsules, in treating bacterial vaginosis (BV), vulvovaginal candidiasis (VVC) or recurrent vulvovaginal candidiasis disease (RVVC) [Estromineral Probiogel (EPB) in Italy, or Saugella Probiogel; Meda Pharma - Mylan Group]. There was a statistically significant improvement in pruritus, burning, vulvovaginal oedema and erythema, dyspareunia and vaginal secretions in all diagnostic groups. At the end of the study, the microbiological evaluation was normal in 80.0% of cases with BV, 62.5% of cases with VVC and 100.0% with RVVC. The clinical data allow EPB to be recommended in the acute treatment of VVC and BV, suggesting that EPB is a useful maintenance treatment if there are recurrent episodes. Controlled studies are needed to confirm the efficacy of EPB in the treatment of recurrences and to identify the most appropriate dosage regimen.}, } @article {pmid29874388, year = {2018}, author = {Montagnani, F and Rossetti, B and Vannoni, A and Cusi, MG and De Luca, A}, title = {Laboratory diagnosis of Mycoplasma pneumoniae infections: data analysis from clinical practice.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {203-207}, pmid = {29874388}, issn = {1121-7138}, mesh = {Adult ; Aged ; Aged, 80 and over ; Antibodies, Bacterial/blood ; Female ; Humans ; Immunoglobulin G/blood ; Immunoglobulin M/blood ; Male ; Middle Aged ; Mycoplasma Infections/blood/*diagnosis/microbiology ; *Mycoplasma pneumoniae ; Polymerase Chain Reaction/*methods ; Respiratory Tract Infections/blood/diagnosis/*microbiology ; Retrospective Studies ; *Serologic Tests ; }, abstract = {An etiological diagnosis of respiratory infections caused by Mycoplasma pneumoniae is particularly challenging due to the lack of a definite standard test. This study aimed to analyse the correlation and combination of diagnostic results obtained from direct and indirect assays (Mycoplasma pneumoniae DNA by PCR and serology) in use at a first level diagnostic laboratory. Samples from patients with respiratory infections tested for M. pneumoniae during routine clinical practice were retrospectively analysed. In pediatric patients <15 years old, we documented a significantly higher proportion of IgM positive results (23.6% versus 3.9% in ≥15-year-old patients, p<0.0001) but a lower IgM specificity (false positive IgM 34.8% versus 12.2% in ≥15 years old patients, p 0.01), as verified by seroconversion. A small percentage (4%) of respiratory samples were positive for M. pneumoniae DNA regardless of age and type of sample. Assuming IgM positivity as the reference standard, PCR showed a total lack of sensitivity in patients <15 years old and 20% sensitivity in children <15 years old; specificity was 95% in both age groups. Agreement between PCR and IgM serology was slight (Cohen's kappa 0.09). According to our data, no single diagnostic test could be considered optimal for M. pneumoniae detection and improved assays are required.}, } @article {pmid29874387, year = {2018}, author = {Bonvicini, F and Lianza, M and Mandrone, M and Poli, F and Gentilomi, GA and Antognoni, F}, title = {Hemidesmus indicus (L.) R. Br. extract inhibits the early step of herpes simplex type 1 and type 2 replication.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {187-194}, pmid = {29874387}, issn = {1121-7138}, mesh = {Animals ; Antiviral Agents/chemistry/pharmacology ; Cell Survival ; Cercopithecus aethiops ; Dose-Response Relationship, Drug ; Glycoside Hydrolase Inhibitors/chemistry/pharmacology ; Hemidesmus/*chemistry ; Herpesvirus 1, Human/drug effects/*physiology ; Herpesvirus 2, Human/drug effects/*physiology ; Plant Extracts/administration & dosage/chemistry/*pharmacology ; Vero Cells ; Virus Replication/*drug effects ; alpha-Glucosidases/metabolism ; }, abstract = {Herpes simplex virus types 1 (HSV-1) and 2 (HSV-2) cause several clinically relevant syndromes in both adults and neonates. Despite the availability of efficient anti-HSV agents, the search for new therapeutic approaches is highly encouraged due to the increasing drug resistance of virus strains. Medicinal plants represent a source of potential bioactive compounds. In this context we evaluated the anti-herpetic activity of Hemidesmus indicus (L.) R. Br., a plant widely used in traditional Indian medicine. The hydroalcoholic extract prepared from roots was characterized by NMR and HPLC analysis and assayed in vitro by CPE reduction and virus infectivity assays to define its anti-viral effect. The extract's mechanism of action was investigated by virucidal and time-of-addition assays and by in vitro α-glucosidase inhibitory assay. The extract exhibited a remarkable anti-herpetic activity at 100 mg/mL, at non-cytotoxic concentration, through multiple mechanisms: it reduced the infectivity of viral particles released from infected cells possibly through its anti-ER α-glucosidase inhibitory activity and it inhibited the beginning stage of HSV infection acting as a virucide agent and/or preventing virus attachment to the host cell surface.}, } @article {pmid29874386, year = {2018}, author = {Genc, GE and Demir, M and Yaman, G and Kayar, B and Koksal, F and Satana, D}, title = {Evaluation of MALDI-TOF MS for identification of nontuberculous mycobacteria isolated from clinical specimens in mycobacteria growth indicator tube medium.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {214-219}, pmid = {29874386}, issn = {1121-7138}, mesh = {Heat-Shock Proteins/genetics ; Humans ; Mycobacterium Infections, Nontuberculous/*diagnosis/*microbiology ; Nontuberculous Mycobacteria/genetics/*isolation & purification ; Nucleic Acid Amplification Techniques ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {Nowadays, there is a rising worldwide incidence of diseases caused by nontuberculous mycobacteria (NTM) species, especially in immunocompromised patients and those with underlying chronic pulmonary diseases. Recently, matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) became a method of choice for the identification of NTM species. The aim of this study was to evaluate MALDI-TOF MS for the identification of NTM isolates compared to the PCR-restriction enzyme analysis (PRA)-hsp65 method. In this study, a total of 152 NTM strains isolated from various clinical specimens were retrospectively analysed. MALDI-TOF MS successfully identified 148 (97.4%) of the 152 NTM isolates but failed to identify four (2.6%) of them. Bruker mycobacteria library gave spectral scores higher than 2.0 for 45 (29.6%) of NTM isolates, between 1.6 and 2.0 for 98 (64.5%) of NTM isolates, and lower than 1.6 for nine (5.9%) NTM isolates. The discordant results between MALDI-TOF MS and PRA-hsp65 analysis were confirmed by sequence analysis. In conclusion, MALDI-TOF MS is a technique capable of performing accurate, rapid, cost-effective, and easy identification of NTM isolates.}, } @article {pmid29874385, year = {2018}, author = {Conte, MP and Superti, F and Moio, M and Ammendolia, MG and Longhi, C and Aleandri, M and Marazzato, M and Goldoni, P and Parisi, P and Borab, Z and Palamara, AT and Carlesimo, B}, title = {Bacterial biofilm associated with a case of capsular contracture.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {238-241}, pmid = {29874385}, issn = {1121-7138}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/isolation & purification ; Bacterial Infections/*microbiology/pathology ; *Biofilms ; Breast Implants/*adverse effects ; Female ; Humans ; Microbial Sensitivity Tests ; }, abstract = {Capsular contracture is one of the most common complications of implant-based breast augmentation. Despite its prevalence, the etiology of capsular contracture remains controversial although the surface texture of the breast implant, the anatomical position of the prosthesis and the presence of bacterial biofilm could be considered trigger factors. In fact, all medical implants are susceptible to bacterial colonization and biofilm formation. The present study demonstrated the presence of microbial biofilm constituted by cocci in a breast implant obtained from a patient with Baker grade II capsular contracture. This suggests that subclinical infection can be present and involved in low grade capsular contracture.}, } @article {pmid29874104, year = {2018}, author = {Duggal, P and Petri, WA}, title = {Does Malnutrition Have a Genetic Component?.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {247-262}, doi = {10.1146/annurev-genom-083117-021340}, pmid = {29874104}, issn = {1545-293X}, abstract = {Malnutrition is a complex disorder, defined by an imbalance, excess, or deficiency of nutrient intake. The visible signs of malnutrition are stunted growth and wasting, but malnourished children are also more likely to have delays in neurocognitive development, vaccine failure, and susceptibility to infection. Despite malnutrition being a major global health problem, we do not yet understand the pathogenesis of this complex disorder. Although lack of food is a major contributor to childhood malnutrition, it is not the sole cause. The mother's prenatal nutritional status, enteric infections, and intestinal inflammation also contribute to the risk of childhood malnutrition and recovery. Here, we discuss another potential risk factor, host and maternal genetics, that may play a role in the risk of malnutrition via several biological pathways. Understanding the genetic risks of malnutrition may help to identify ideal targets for intervention and treatment of malnutrition.}, } @article {pmid29873875, year = {2018}, author = {Warwell, MV and Shaw, RG}, title = {Phenotypic selection on growth rhythm in whitebark pine under climatic conditions warmer than seed origins.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {9}, pages = {1284-1299}, doi = {10.1111/jeb.13301}, pmid = {29873875}, issn = {1420-9101}, support = {//USDA Rocky Mountain Research Station/ ; }, abstract = {Growth rhythm that is well synchronized with seasonal changes in local climatic conditions is understood to enhance fitness; however, rapid ongoing climate change threatens to disrupt this synchrony. To evaluate phenotypic selection on growth rhythm under expected warmer and drier future climate, seedlings from 49 populations of whitebark pine (Pinus albicaulis Engelm.) were grown and measured over more than 10 years in two common garden field experiments on sites that approximate the projected future climate of the seed origins. Selection on growth rhythm was assessed by relating individual plant fitness to timing and rate of shoot elongation. Differential survival clearly evidenced selection on growth rhythm. We detected directional and stabilizing selection that varied in magnitude between experimental sites and among years. The observed phenotypic selection supports the interpretation of clinal variation among populations within tree species as reflecting adaptive variation in response to past natural selection mediated by climate. To the extent that growth rhythm is heritable, results of the present study suggest evolution of whitebark pine toward a more distinct timing of shoot elongation and generally more rapid elongation in the immediate next generation under ongoing climate change in environments similar to the study sites.}, } @article {pmid29873717, year = {2018}, author = {In 't Zandt, MH and de Jong, AE and Slomp, CP and Jetten, MS}, title = {The hunt for the most-wanted chemolithoautotrophic spookmicrobes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, pmid = {29873717}, issn = {1574-6941}, abstract = {Microorganisms are the drivers of biogeochemical methane and nitrogen cycles. Essential roles of chemolithoautotrophic microorganisms in these cycles were predicted long before their identification. Dedicated enrichment procedures, metagenomics surveys and single-cell technologies have enabled the identification of several new groups of most-wanted spookmicrobes, including novel methoxydotrophic methanogens that produce methane from methylated coal compounds and acetoclastic 'Candidatus Methanothrix paradoxum', which is active in oxic soils. The resultant energy-rich methane can be oxidized via a suite of electron acceptors. Recently, 'Candidatus Methanoperedens nitroreducens' ANME-2d archaea and 'Candidatus Methylomirabilis oxyfera' bacteria were enriched on nitrate and nitrite under anoxic conditions with methane as an electron donor. Although 'Candidatus Methanoperedens nitroreducens' and other ANME archaea can use iron citrate as an electron acceptor in batch experiments, the quest for anaerobic methane oxidizers that grow via iron reduction continues. In recent years, the nitrogen cycle has been expanded by the discovery of various ammonium-oxidizing prokaryotes, including ammonium-oxidizing archaea, versatile anaerobic ammonium-oxidizing (anammox) bacteria and complete ammonium-oxidizing (comammox) Nitrospira bacteria. Several biogeochemical studies have indicated that ammonium conversion occurs under iron-reducing conditions, but thus far no microorganism has been identified. Ultimately, iron-reducing and sulfate-dependent ammonium-oxidizing microorganisms await discovery.}, } @article {pmid29873630, year = {2018}, author = {Ou-Yang, TN and Xia, F and Qiu, LH}, title = {Acidicapsa dinghuensis sp. nov., a novel acidobacterium isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2364-2369}, doi = {10.1099/ijsem.0.002846}, pmid = {29873630}, issn = {1466-5034}, mesh = {Acidobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A bacterial strain, designated 4GSKXT, isolated from the forest soil of Dinghushan Biosphere Reserve, Guangdong Province, PR China (112° 31' E 23° 10' N), is proposed as a novel species of the genus Acidicapsa. Cells of strain 4GSKXT were aerobic, non-motile, Gram-stain-negative short rods that multiplied by binary division. The strain grew at 12-37 °C (optimum, 25-30 °C), pH 4.0-6.5 (optimum, pH 4.5-5.0) and NaCl concentrations of 0-1.0 % (w/v; optimum, 0 %). Strain 4GSKXT utilized various carbon sources as growth substrates, including both sugars and amino acids. The major fatty acids (>10 %) were iso-C15 : 0 (48.8 %) and iso-C17 : 1ω9c/C16 : 0 10-methyl (14.7 %). The major polar lipids were phosphatidylethanolamine, an unidentified glycolipid, three unidentified phospholipids and two unidentified aminophospholipids. The only quinone detected was MK-8 and the DNA G+C content was 52.8 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain 4GSKXT belongs to the genus Acidicapsa in the family Acidobacteriaceae in subdivision 1 of the phylum Acidobacteria, with the highest similarity of 97.1 % to Acidicapsa ligni WH120T. Based on all phenotypic, chemotaxonomic and phylogenetic data obtained, it is proposed as a novel species of genus Acidicapsa, for which the name Acidicapsa dinghuensis sp. nov. is proposed, with 4GSKXT (=CGMCC 1.15449T=LMG 29213T) as the type strain.}, } @article {pmid29873629, year = {2018}, author = {Oren, A and Garrity, GM and Parte, AC}, title = {Why are so many effectively published names of prokaryotic taxa never validated?.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2125-2129}, doi = {10.1099/ijsem.0.002851}, pmid = {29873629}, issn = {1466-5034}, mesh = {Bacteria/*classification ; Publishing/*trends ; *Terminology as Topic ; }, abstract = {Nearly half of the new names of prokaryotic taxa between the ranks of subspecies and class that were effectively published in journals other than the International Journal of Systematic and Evolutionary Microbiology (IJSEM) in the period 2014-2017 were never submitted for validation. A survey of such effectively published names that include information on the etymology of the name, a description of the taxon, and for species and subspecies generally at least one culture collection deposit, shows that for more than 150 such effectively published names per year on average, validation was never requested. To prevent further accumulation in the literature of names of prokaryotic taxa without standing in the nomenclature, we call upon authors of taxon descriptions and on the editors of the journals handling such papers to be more aware of the duty to validate effectively published names.}, } @article {pmid29873425, year = {2018}, author = {Semenov, GA and Koblik, EA and Red'kin, YA and Badyaev, AV}, title = {Extensive phenotypic diversification coexists with little genetic divergence and a lack of population structure in the White Wagtail subspecies complex (Motacilla alba).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1093-1108}, doi = {10.1111/jeb.13305}, pmid = {29873425}, issn = {1420-9101}, abstract = {Geographically clustered phenotypes often demonstrate consistent patterns in molecular markers, particularly mitochondrial DNA (mtDNA) traditionally used in phylogeographic studies. However, distinct evolutionary trajectories among traits and markers can lead to their discordance. First, geographic structure in phenotypic traits and nuclear molecular markers can be co-aligned but inconsistent with mtDNA (mito-nuclear discordance). Alternatively, phenotypic variation can have little to do with patterns in neither mtDNA nor nuclear markers. Disentangling between these distinct patterns can provide insight into the role of selection, demography and gene flow in population divergence. Here, we examined a previously reported case of strong inconsistency between geographic structure in mtDNA and plumage traits in a widespread polytypic bird species, the White Wagtail (Motacilla alba). We tested whether this pattern is due to mito-nuclear discordance or discrepancy between morphological evolution and both nuclear and mtDNA markers. We analysed population differentiation and structure across six out of nine commonly recognized subspecies using 17 microsatellite loci and a combination of microsatellites and plumage indices in a comprehensively sampled region of a contact between two subspecies. We did not find support for the mito-nuclear discordance hypothesis: nuclear markers indicated a subtle signal of genetic clustering only partially consistent with plumage groups, similar to previous findings that relied on mtDNA. We discuss evolutionary factors that could have shaped the intricate patterns of phenotypic diversification in the White wagtail and the role that repeated selection on plumage 'hotspots' and hybridization may have played.}, } @article {pmid29873175, year = {2018}, author = {Fang, J and Chen, T and Pan, Q and Wang, Q}, title = {Generation of albino medaka (Oryzias latipes) by CRISPR/Cas9.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {4}, pages = {242-246}, doi = {10.1002/jez.b.22808}, pmid = {29873175}, issn = {1552-5015}, abstract = {CRISPR/Cas9 system is a powerful tool to produce the genetic modification in plants and animals such as mouse and zebrafish. However, this technique was less reported in fish model medaka (Oryzias latipes). Here, we describe an efficient and rapid procedure for genome editing in medaka tyr and generate a stable albino strain. The Cas9 mRNA and gRNA for tyr gene were injected into the embryos of orange-red medaka, and the tyr gene was disrupted in more than 90% of embryos in F0 and F1, which were validated by observation and sequencing of targeted locus. The pigment cells were largely decreased in the mutant medaka because open reading frames of tyr were shifted near the targeted locus, generating albino medaka. Taken together, this method provides a detailed procedure to generate the genetic modification medaka by using an optimized CRISPR/Cas9 system, and the new albino medaka provides an important research platform to study the pigmentation.}, } @article {pmid29872901, year = {2018}, author = {Chaudhary, DK and Dahal, RH and Kim, J}, title = {Sphingomonas montis sp. nov., Isolated from Forest Soil of Low-Altitude Mountain.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29872901}, issn = {1432-0991}, support = {2016R1D1A1A09916982//Ministry of Education/ ; }, abstract = {Strain DRJ-4T was isolated from forest soil of a low-altitude mountain and was taxonomically characterized by a polyphasic approach. This strain was yellow-colored, Gram-stain-negative, strictly aerobic, motile, non-sporulating, catalase-positive, oxidase-negative, and rod-shaped. Strain DRJ-4T was able to grow at 20-42 °C, pH 6.5-10.0, and 0-1.0% (w/v) NaCl concentration. Based on the 16S rRNA gene sequence analysis, strain DRJ-4T formed a distinct lineage within the members of the family Sphingomonadaceae of the phylum Proteobacteria and moderately related to Sphingomonas faucium E62-3T (96.67% sequence similarity), 'Sphingosinicella ginsenosidimutans' BS11 (96.45% sequence similarity), Sphingosinicella vermicomposti YC7378T (96.27% sequence similarity), and Sphingobium boeckii 469T (95.82% sequence similarity). The sole respiratory quinone was ubiquinone Q-10 and the major polyamine was homospermidine. The polar lipid profile revealed the presence of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine, and sphingoglycolipid. The predominant fatty acids of strain DRJ-4T were summed feature 8 (C18:1ω7c and/or C18:1ω6c), summed feature 3 (C16:1ω7c and/or C16:1ω6c), C16:0, and C17:1ω6c. The genomic DNA G + C was 64.0 mol %. On the basis of phenotypic, genotypic, and phylogenetic analysis, strain DRJ-4T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas montis sp. nov. is proposed. The type strain of Sphingomonas montis is DRJ-4T (= KEMB 9005-708T = NBRC 113142T).}, } @article {pmid29872216, year = {2018}, author = {Pingault, JB and O'Reilly, PF and Schoeler, T and Ploubidis, GB and Rijsdijk, F and Dudbridge, F}, title = {Using genetic data to strengthen causal inference in observational research.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {566-580}, doi = {10.1038/s41576-018-0020-3}, pmid = {29872216}, issn = {1471-0064}, abstract = {Causal inference is essential across the biomedical, behavioural and social sciences.By progressing from confounded statistical associations to evidence of causal relationships, causal inference can reveal complex pathways underlying traits and diseases and help to prioritize targets for intervention. Recent progress in genetic epidemiology - including statistical innovation, massive genotyped data sets and novel computational tools for deep data mining - has fostered the intense development of methods exploiting genetic data and relatedness to strengthen causal inference in observational research. In this Review, we describe how such genetically informed methods differ in their rationale, applicability and inherent limitations and outline how they should be integrated in the future to offer a rich causal inference toolbox.}, } @article {pmid29872215, year = {2018}, author = {Wing, RA and Purugganan, MD and Zhang, Q}, title = {The rice genome revolution: from an ancient grain to Green Super Rice.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {505-517}, doi = {10.1038/s41576-018-0024-z}, pmid = {29872215}, issn = {1471-0064}, abstract = {Rice is a staple crop for half the world's population, which is expected to grow by 3 billion over the next 30 years. It is also a key model for studying the genomics of agroecosystems. This dual role places rice at the centre of an enormous challenge facing agriculture: how to leverage genomics to produce enough food to feed an expanding global population. Scientists worldwide are investigating the genetic variation among domesticated rice species and their wild relatives with the aim of identifying loci that can be exploited to breed a new generation of sustainable crops known as Green Super Rice.}, } @article {pmid29872210, year = {2018}, author = {}, title = {Europe's top science advisers send clear message on food production.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {6}, doi = {10.1038/d41586-018-05327-2}, pmid = {29872210}, issn = {1476-4687}, mesh = {Crop Production/*methods ; *Decision Making ; Europe ; European Union ; *Food Supply ; *Pesticides/supply & distribution ; }, } @article {pmid29872209, year = {2018}, author = {Sukhdev, P}, title = {Smarter metrics will help fix our food system.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {7}, doi = {10.1038/d41586-018-05328-1}, pmid = {29872209}, issn = {1476-4687}, mesh = {Animals ; Crop Production/*methods/*statistics & numerical data ; *Evaluation Studies as Topic ; Fisheries/statistics & numerical data ; Food Supply/*standards/*statistics & numerical data ; Humans ; Organic Agriculture/methods/statistics & numerical data ; Pesticides/adverse effects ; Public Health ; }, } @article {pmid29872208, year = {2018}, author = {}, title = {Zombie ants' final resting place sealed by the trees.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {8}, doi = {10.1038/d41586-018-05277-9}, pmid = {29872208}, issn = {1476-4687}, } @article {pmid29872206, year = {2018}, author = {Perkel, JM}, title = {Map-making on a budget.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {147-148}, doi = {10.1038/d41586-018-05331-6}, pmid = {29872206}, issn = {1476-4687}, } @article {pmid29872205, year = {2018}, author = {Price, GJ and Louys, J and Faith, JT and Lorenzen, E and Westaway, MC}, title = {Big data little help in megafauna mysteries.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {23-25}, doi = {10.1038/d41586-018-05330-7}, pmid = {29872205}, issn = {1476-4687}, mesh = {Animals ; Climate Change/*history ; *Extinction, Biological ; *Fossils ; Geologic Sediments/microbiology ; History, Ancient ; Human Activities/*history ; Macropodidae ; Mammoths ; *Meta-Analysis as Topic ; Perissodactyla ; Sloths ; Species Specificity ; Time Factors ; }, } @article {pmid29872204, year = {2018}, author = {Adam, GC}, title = {Two artificial synapses are better than one.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {39-40}, doi = {10.1038/d41586-018-05297-5}, pmid = {29872204}, issn = {1476-4687}, mesh = {*Neural Networks (Computer) ; *Synapses ; }, } @article {pmid29872203, year = {2018}, author = {Patricola, CM}, title = {Tropical cyclones are becoming sluggish.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {36-37}, doi = {10.1038/d41586-018-05303-w}, pmid = {29872203}, issn = {1476-4687}, mesh = {*Cyclonic Storms ; *Tropical Climate ; }, } @article {pmid29872202, year = {2018}, author = {Marín, C}, title = {Astronomy was his undoing: why a Colombian pioneer got shot.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {30}, doi = {10.1038/d41586-018-05341-4}, pmid = {29872202}, issn = {1476-4687}, } @article {pmid29872201, year = {2018}, author = {Kusiak, A}, title = {Create jobs in cleaning up the environment.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {30}, doi = {10.1038/d41586-018-05342-3}, pmid = {29872201}, issn = {1476-4687}, mesh = {Conservation of Natural Resources/*economics/*methods ; Ecology/*economics ; Employment/*trends ; Environmental Pollutants/isolation & purification ; Recycling/economics ; Workforce ; }, } @article {pmid29872200, year = {2018}, author = {Laurance, WF}, title = {Wanted: AI experts to map road-building boom.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {30}, doi = {10.1038/d41586-018-05343-2}, pmid = {29872200}, issn = {1476-4687}, } @article {pmid29872199, year = {2018}, author = {Buzzard, S and Cook, J and Maslakov, A}, title = {Arctic collaboration transcends political tensions.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {30}, doi = {10.1038/d41586-018-05340-5}, pmid = {29872199}, issn = {1476-4687}, mesh = {Arctic Regions ; Communication Barriers ; Congresses as Topic ; *Cooperative Behavior ; *Politics ; Research/*organization & administration ; Research Personnel/*organization & administration ; Russia ; United Kingdom ; Workforce ; }, } @article {pmid29872198, year = {2018}, author = {Vesper, I}, title = {Europe's top science funder shows high-risk research pays off.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {16-17}, doi = {10.1038/d41586-018-05325-4}, pmid = {29872198}, issn = {1476-4687}, mesh = {Europe ; European Union/economics ; Financing, Organized/economics/*statistics & numerical data ; Policy Making ; Qualitative Research ; Research/*economics/*standards/statistics & numerical data ; *Research Support as Topic/economics ; *Risk ; }, } @article {pmid29872194, year = {2018}, author = {}, title = {Marketing personalized cancer treatments requires careful language.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {5-6}, doi = {10.1038/d41586-018-05323-6}, pmid = {29872194}, issn = {1476-4687}, mesh = {Advertising as Topic/ethics/standards ; *Communication ; Hope ; Humans ; *Language ; Male ; Marketing/*ethics/standards ; Neoplasms/*drug therapy/genetics/mortality/pathology ; Patients/*psychology ; Precision Medicine/*ethics/standards ; Survival Rate ; }, } @article {pmid29872193, year = {2018}, author = {Tollefson, J}, title = {US EPA science advisers question 'secret science' rule on data transparency.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {15}, doi = {10.1038/d41586-018-05319-2}, pmid = {29872193}, issn = {1476-4687}, mesh = {Access to Information/*legislation & jurisprudence ; *Dissent and Disputes ; Environmental Pollution/legislation & jurisprudence/prevention & control ; Greenhouse Effect/legislation & jurisprudence ; Research/*legislation & jurisprudence ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence ; }, } @article {pmid29872192, year = {2018}, author = {}, title = {Synthetic nerve flexes a cockroach's muscle.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {8}, doi = {10.1038/d41586-018-05322-7}, pmid = {29872192}, issn = {1476-4687}, } @article {pmid29872191, year = {2018}, author = {}, title = {The powerful genes that might have supersized the human brain.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {9}, doi = {10.1038/d41586-018-05321-8}, pmid = {29872191}, issn = {1476-4687}, } @article {pmid29872190, year = {2018}, author = {}, title = {Hundreds of methane dunes nestle at the base of Pluto's mountains.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {9}, doi = {10.1038/d41586-018-05320-9}, pmid = {29872190}, issn = {1476-4687}, } @article {pmid29872189, year = {2018}, author = {Guglielmi, G}, title = {Million-dollar Kavli prize recognizes scientist scooped on CRISPR.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {17-18}, doi = {10.1038/d41586-018-05308-5}, pmid = {29872189}, issn = {1476-4687}, mesh = {Animals ; Astronomy/standards ; *Awards and Prizes ; *CRISPR-Cas Systems ; *Gene Editing ; Hearing ; Humans ; Mice ; Neurosciences/standards ; Patents as Topic/legislation & jurisprudence ; }, } @article {pmid29872188, year = {2018}, author = {Abbott, A}, title = {Max Planck scientists criticize handling of animal-rights charges against leading neuroscientist.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {13-14}, doi = {10.1038/d41586-018-05187-w}, pmid = {29872188}, issn = {1476-4687}, mesh = {Academies and Institutes/economics/*organization & administration ; Animal Rights/*legislation & jurisprudence ; Animals ; Animals, Laboratory ; *Dissent and Disputes ; Germany ; Leadership ; Neurosciences/economics/*legislation & jurisprudence/methods ; Primates ; Research Personnel/*legislation & jurisprudence/psychology ; Societies, Scientific/economics/*organization & administration ; }, } @article {pmid29872187, year = {2018}, author = {}, title = {The invasive snail that fooled zoologists.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {8-9}, doi = {10.1038/d41586-018-05298-4}, pmid = {29872187}, issn = {1476-4687}, } @article {pmid29872186, year = {2018}, author = {}, title = {Deaths from catastrophic storm vastly exceeded initial estimate.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {9}, doi = {10.1038/d41586-018-05295-7}, pmid = {29872186}, issn = {1476-4687}, } @article {pmid29872185, year = {2018}, author = {}, title = {Ancient poo reveals extinct dogs crunched big bones.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {9}, doi = {10.1038/d41586-018-05294-8}, pmid = {29872185}, issn = {1476-4687}, } @article {pmid29872184, year = {2018}, author = {}, title = {Coppery inks paint an underwater rainbow.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {9}, doi = {10.1038/d41586-018-05282-y}, pmid = {29872184}, issn = {1476-4687}, } @article {pmid29872183, year = {2018}, author = {}, title = {Drilling reveals the Great Barrier Reef's restless past.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {8}, doi = {10.1038/d41586-018-05276-w}, pmid = {29872183}, issn = {1476-4687}, } @article {pmid29872182, year = {2018}, author = {Pourquié, O}, title = {Human embryonic stem cells get organized.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {35-36}, doi = {10.1038/d41586-018-05115-y}, pmid = {29872182}, issn = {1476-4687}, mesh = {Cell Culture Techniques ; Cell Differentiation ; *Embryonic Stem Cells ; *Human Embryonic Stem Cells ; Humans ; }, } @article {pmid29872181, year = {2018}, author = {Alonso, JM}, title = {Motion processing picks up speed in the brain.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {38-39}, doi = {10.1038/d41586-018-04289-9}, pmid = {29872181}, issn = {1476-4687}, support = {R01 EY005253/EY/NEI NIH HHS/United States ; R01 EY020679/EY/NEI NIH HHS/United States ; }, mesh = {*Brain ; Motion ; *Motion Perception ; Photic Stimulation ; }, } @article {pmid29872180, year = {2018}, author = {Hoffmann, S and Krause, DW}, title = {A 3D view of early mammals.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {32-33}, doi = {10.1038/d41586-018-05134-9}, pmid = {29872180}, issn = {1476-4687}, mesh = {Animals ; *Biological Evolution ; *Mammals ; }, } @article {pmid29871954, year = {2018}, author = {Nyerges, Á and Csörgő, B and Draskovits, G and Kintses, B and Szili, P and Ferenc, G and Révész, T and Ari, E and Nagy, I and Bálint, B and Vásárhelyi, BM and Bihari, P and Számel, M and Balogh, D and Papp, H and Kalapis, D and Papp, B and Pál, C}, title = {Directed evolution of multiple genomic loci allows the prediction of antibiotic resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5726-E5735}, pmid = {29871954}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 084314//Wellcome Trust/United Kingdom ; 648364//European Research Council/International ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/*genetics ; Ciprofloxacin/pharmacology ; Drug Resistance, Multiple, Bacterial/drug effects/*genetics ; Evolution, Molecular ; Genetic Loci/*genetics ; Genome, Bacterial/*genetics ; Genomics/methods ; Mutation/genetics ; Mutation Rate ; Trimethoprim/pharmacology ; }, abstract = {Antibiotic development is frequently plagued by the rapid emergence of drug resistance. However, assessing the risk of resistance development in the preclinical stage is difficult. Standard laboratory evolution approaches explore only a small fraction of the sequence space and fail to identify exceedingly rare resistance mutations and combinations thereof. Therefore, new rapid and exhaustive methods are needed to accurately assess the potential of resistance evolution and uncover the underlying mutational mechanisms. Here, we introduce directed evolution with random genomic mutations (DIvERGE), a method that allows an up to million-fold increase in mutation rate along the full lengths of multiple predefined loci in a range of bacterial species. In a single day, DIvERGE generated specific mutation combinations, yielding clinically significant resistance against trimethoprim and ciprofloxacin. Many of these mutations have remained previously undetected or provide resistance in a species-specific manner. These results indicate pathogen-specific resistance mechanisms and the necessity of future narrow-spectrum antibacterial treatments. In contrast to prior claims, we detected the rapid emergence of resistance against gepotidacin, a novel antibiotic currently in clinical trials. Based on these properties, DIvERGE could be applicable to identify less resistance-prone antibiotics at an early stage of drug development. Finally, we discuss potential future applications of DIvERGE in synthetic and evolutionary biology.}, } @article {pmid29871953, year = {2018}, author = {Susman, L and Kohram, M and Vashistha, H and Nechleba, JT and Salman, H and Brenner, N}, title = {Individuality and slow dynamics in bacterial growth homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5679-E5687}, pmid = {29871953}, issn = {1091-6490}, mesh = {Cell Cycle/physiology ; Cell Size ; Escherichia coli/*cytology/*physiology ; Homeostasis/*physiology ; }, abstract = {Microbial growth and division are fundamental processes relevant to many areas of life science. Of particular interest are homeostasis mechanisms, which buffer growth and division from accumulating fluctuations over multiple cycles. These mechanisms operate within single cells, possibly extending over several division cycles. However, all experimental studies to date have relied on measurements pooled from many distinct cells. Here, we disentangle long-term measured traces of individual cells from one another, revealing subtle differences between temporal and pooled statistics. By analyzing correlations along up to hundreds of generations, we find that the parameter describing effective cell size homeostasis strength varies significantly among cells. At the same time, we find an invariant cell size, which acts as an attractor to all individual traces, albeit with different effective attractive forces. Despite the common attractor, each cell maintains a distinct average size over its finite lifetime with suppressed temporal fluctuations around it, and equilibration to the global average size is surprisingly slow ([Formula: see text] cell cycles). To show a possible source of variable homeostasis strength, we construct a mathematical model relying on intracellular interactions, which integrates measured properties of cell size with those of highly expressed proteins. Effective homeostasis strength is then influenced by interactions and by noise levels and generally varies among cells. A predictable and measurable consequence of variable homeostasis strength appears as distinct oscillatory patterns in cell size and protein content over many generations. We discuss implications of our results to understanding mechanisms controlling division in single cells and their characteristic timescales.}, } @article {pmid29871952, year = {2018}, author = {Greenham, K and McClung, CR}, title = {Time to build on good design: Resolving the temporal dynamics of gene regulatory networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6325-6327}, pmid = {29871952}, issn = {1091-6490}, mesh = {Algorithms ; *Gene Regulatory Networks ; *Models, Genetic ; Software ; }, } @article {pmid29871951, year = {2018}, author = {Tabib, Y and Jaber, NS and Nassar, M and Capucha, T and Mizraji, G and Nir, T and Koren, N and Aizenbud, I and Maimon, A and Eli-Berchoer, L and Wilensky, A and Burstyn-Cohen, T and Hovav, AH}, title = {Cell-intrinsic regulation of murine epidermal Langerhans cells by protein S.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5736-E5745}, pmid = {29871951}, issn = {1091-6490}, mesh = {Animals ; Bone Marrow/metabolism ; Carrier Proteins/*metabolism ; Cell Differentiation/physiology ; Epidermis/*metabolism ; Homeostasis/physiology ; Keratinocytes/metabolism ; Langerhans Cells/*metabolism ; Mice ; Mice, Inbred C57BL ; Monocytes/metabolism ; Protein S/*metabolism ; Proto-Oncogene Proteins/metabolism ; Receptor Protein-Tyrosine Kinases/metabolism ; Signal Transduction/physiology ; c-Mer Tyrosine Kinase/metabolism ; }, abstract = {AXL, a member of the TYRO3, AXL, and MERTK (TAM) receptor tyrosine kinase family, has been shown to play a role in the differentiation and activation of epidermal Langerhans cells (LCs). Here, we demonstrate that growth arrest-specific 6 (GAS6) protein, the predominant ligand of AXL, has no impact on LC differentiation and homeostasis. We thus examined the role of protein S (PROS1), the other TAM ligand acting primarily via TYRO3 and MERTK, in LC function. Genetic ablation of PROS1 in keratinocytes resulted in a typical postnatal differentiation of LCs; however, a significant reduction in LC frequencies was observed in adult mice due to increased apoptosis. This was attributed to altered expression of cytokines involved in LC development and tissue homeostasis within keratinocytes. PROS1 was then excised in LysM+ cells to target LCs at early embryonic developmental stages, as well as in adult monocytes that also give rise to LCs. Differentiation and homeostasis of LCs derived from embryonic precursors was not affected following Pros1 ablation. However, differentiation of LCs from bone marrow (BM) precursors in vitro was accelerated, as was their capability to reconstitute epidermal LCs in vivo. These reveal an inhibitory role for PROS1 on BM-derived LCs. Collectively, this study highlights a cell-specific regulation of LC differentiation and homeostasis by TAM signaling.}, } @article {pmid29871950, year = {2018}, author = {Gerrick, ER and Barbier, T and Chase, MR and Xu, R and François, J and Lin, VH and Szucs, MJ and Rock, JM and Ahmad, R and Tjaden, B and Livny, J and Fortune, SM}, title = {Small RNA profiling in Mycobacterium tuberculosis identifies MrsI as necessary for an anticipatory iron sparing response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6464-6469}, pmid = {29871950}, issn = {1091-6490}, support = {R15 GM102755/GM/NIGMS NIH HHS/United States ; U19 AI107774/AI/NIAID NIH HHS/United States ; }, mesh = {Gene Expression Profiling/methods ; Gene Expression Regulation, Bacterial/genetics ; Iron/metabolism ; Mycobacterium tuberculosis/*genetics/metabolism ; RNA, Bacterial/*genetics ; RNA, Small Untranslated/*genetics ; Sequence Analysis, RNA/methods ; }, abstract = {One key to the success of Mycobacterium tuberculosis as a pathogen is its ability to reside in the hostile environment of the human macrophage. Bacteria adapt to stress through a variety of mechanisms, including the use of small regulatory RNAs (sRNAs), which posttranscriptionally regulate bacterial gene expression. However, very little is currently known about mycobacterial sRNA-mediated riboregulation. To date, mycobacterial sRNA discovery has been performed primarily in log-phase growth, and no direct interaction between any mycobacterial sRNA and its targets has been validated. Here, we performed large-scale sRNA discovery and expression profiling in M. tuberculosis during exposure to five pathogenically relevant stresses. From these data, we identified a subset of sRNAs that are highly induced in multiple stress conditions. We focused on one of these sRNAs, ncRv11846, here renamed mycobacterial regulatory sRNA in iron (MrsI). We characterized the regulon of MrsI and showed in mycobacteria that it regulates one of its targets, bfrA, through a direct binding interaction. MrsI mediates an iron-sparing response that is required for optimal survival of M. tuberculosis under iron-limiting conditions. However, MrsI is induced by multiple host-like stressors, which appear to trigger MrsI as part of an anticipatory response to impending iron deprivation in the macrophage environment.}, } @article {pmid29871949, year = {2018}, author = {Watanabe, Y and Schneider, R and Barkwill, S and Gonzales-Vigil, E and Hill, JL and Samuels, AL and Persson, S and Mansfield, SD}, title = {Cellulose synthase complexes display distinct dynamic behaviors during xylem transdifferentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {E6366-E6374}, pmid = {29871949}, issn = {1091-6490}, mesh = {Arabidopsis/*enzymology/genetics ; Arabidopsis Proteins/genetics/*metabolism ; Cell Transdifferentiation/*physiology ; Glucosyltransferases/genetics/*metabolism ; Xylem/*enzymology/genetics ; }, abstract = {In plants, plasma membrane-embedded CELLULOSE SYNTHASE (CESA) enzyme complexes deposit cellulose polymers into the developing cell wall. Cellulose synthesis requires two different sets of CESA complexes that are active during cell expansion and secondary cell wall thickening, respectively. Hence, developing xylem cells, which first undergo cell expansion and subsequently deposit thick secondary walls, need to completely reorganize their CESA complexes from primary wall- to secondary wall-specific CESAs. Using live-cell imaging, we analyzed the principles underlying this remodeling. At the onset of secondary wall synthesis, the primary wall CESAs ceased to be delivered to the plasma membrane and were gradually removed from both the plasma membrane and the Golgi. For a brief transition period, both primary wall- and secondary wall-specific CESAs coexisted in banded domains of the plasma membrane where secondary wall synthesis is concentrated. During this transition, primary and secondary wall CESAs displayed discrete dynamic behaviors and sensitivities to the inhibitor isoxaben. As secondary wall-specific CESAs were delivered and inserted into the plasma membrane, the primary wall CESAs became concentrated in prevacuolar compartments and lytic vacuoles. This adjustment in localization between the two CESAs was accompanied by concurrent decreased primary wall CESA and increased secondary wall CESA protein abundance. Our data reveal distinct and dynamic subcellular trafficking patterns that underpin the remodeling of the cellulose biosynthetic machinery, resulting in the removal and degradation of the primary wall CESA complex with concurrent production and recycling of the secondary wall CESAs.}, } @article {pmid29871948, year = {2018}, author = {Norouzzadeh, MS and Nguyen, A and Kosmala, M and Swanson, A and Palmer, MS and Packer, C and Clune, J}, title = {Automatically identifying, counting, and describing wild animals in camera-trap images with deep learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5716-E5725}, pmid = {29871948}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; Animals, Wild/*physiology ; Artificial Intelligence ; Behavior, Animal/*physiology ; Ecology/methods ; Ecosystem ; Humans ; Machine Learning ; Neural Networks (Computer) ; }, abstract = {Having accurate, detailed, and up-to-date information about the location and behavior of animals in the wild would improve our ability to study and conserve ecosystems. We investigate the ability to automatically, accurately, and inexpensively collect such data, which could help catalyze the transformation of many fields of ecology, wildlife biology, zoology, conservation biology, and animal behavior into "big data" sciences. Motion-sensor "camera traps" enable collecting wildlife pictures inexpensively, unobtrusively, and frequently. However, extracting information from these pictures remains an expensive, time-consuming, manual task. We demonstrate that such information can be automatically extracted by deep learning, a cutting-edge type of artificial intelligence. We train deep convolutional neural networks to identify, count, and describe the behaviors of 48 species in the 3.2 million-image Snapshot Serengeti dataset. Our deep neural networks automatically identify animals with >93.8% accuracy, and we expect that number to improve rapidly in years to come. More importantly, if our system classifies only images it is confident about, our system can automate animal identification for 99.3% of the data while still performing at the same 96.6% accuracy as that of crowdsourced teams of human volunteers, saving >8.4 y (i.e., >17,000 h at 40 h/wk) of human labeling effort on this 3.2 million-image dataset. Those efficiency gains highlight the importance of using deep neural networks to automate data extraction from camera-trap images, reducing a roadblock for this widely used technology. Our results suggest that deep learning could enable the inexpensive, unobtrusive, high-volume, and even real-time collection of a wealth of information about vast numbers of animals in the wild.}, } @article {pmid29871947, year = {2018}, author = {Ross, AA and Müller, KM and Weese, JS and Neufeld, JD}, title = {Comprehensive skin microbiome analysis reveals the uniqueness of human skin and evidence for phylosymbiosis within the class Mammalia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5786-E5795}, pmid = {29871947}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Animals ; Bacteria/*genetics ; DNA/genetics ; Humans ; Mammals/*microbiology ; Microbiota/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Skin/*microbiology ; Symbiosis/*genetics ; }, abstract = {Skin is the largest organ of the body and represents the primary physical barrier between mammals and their external environment, yet the factors that govern skin microbial community composition among mammals are poorly understood. The objective of this research was to generate a skin microbiota baseline for members of the class Mammalia, testing the effects of host species, geographic location, body region, and biological sex. Skin from the back, torso, and inner thighs of 177 nonhuman mammals was sampled, representing individuals from 38 species and 10 mammalian orders. Animals were sampled from farms, zoos, households, and the wild. The DNA extracts from all skin swabs were amplified by PCR and sequenced, targeting the V3-V4 regions of bacterial and archaeal 16S rRNA genes. Previously published skin microbiome data from 20 human participants, sampled and sequenced using an identical protocol to the nonhuman mammals, were included to make this a comprehensive analysis. Human skin microbial communities were distinct and significantly less diverse than all other sampled mammalian orders. The factor most strongly associated with microbial community data for all samples was whether the host was a human. Within nonhuman samples, host taxonomic order was the most significant factor influencing skin microbiota, followed by the geographic location of the habitat. By comparing the congruence between host phylogeny and microbial community dendrograms, we observed that Artiodactyla (even-toed ungulates) and Perissodactyla (odd-toed ungulates) had significant congruence, providing evidence of phylosymbiosis between skin microbial communities and their hosts.}, } @article {pmid29871946, year = {2018}, author = {Cole, JM and Symes, DR and Lopes, NC and Wood, JC and Poder, K and Alatabi, S and Botchway, SW and Foster, PS and Gratton, S and Johnson, S and Kamperidis, C and Kononenko, O and De Lazzari, M and Palmer, CAJ and Rusby, D and Sanderson, J and Sandholzer, M and Sarri, G and Szoke-Kovacs, Z and Teboul, L and Thompson, JM and Warwick, JR and Westerberg, H and Hill, MA and Norris, DP and Mangles, SPD and Najmudin, Z}, title = {High-resolution μCT of a mouse embryo using a compact laser-driven X-ray betatron source.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6335-6340}, pmid = {29871946}, issn = {1091-6490}, support = {MC_U142670370//Medical Research Council/United Kingdom ; U42 OD011174/OD/NIH HHS/United States ; 53658//Medical Research Council/United Kingdom ; MC-PC-12004//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Equipment Design ; Lasers ; Light ; Mice/embryology ; Particle Accelerators ; Photons ; Radiography/*methods ; Scattering, Radiation ; X-Ray Microtomography/*methods ; X-Rays ; }, abstract = {In the field of X-ray microcomputed tomography (μCT) there is a growing need to reduce acquisition times at high spatial resolution (approximate micrometers) to facilitate in vivo and high-throughput operations. The state of the art represented by synchrotron light sources is not practical for certain applications, and therefore the development of high-brightness laboratory-scale sources is crucial. We present here imaging of a fixed embryonic mouse sample using a compact laser-plasma-based X-ray light source and compare the results to images obtained using a commercial X-ray μCT scanner. The radiation is generated by the betatron motion of electrons inside a dilute and transient plasma, which circumvents the flux limitations imposed by the solid or liquid anodes used in conventional electron-impact X-ray tubes. This X-ray source is pulsed (duration <30 fs), bright (>1010 photons per pulse), small (diameter <1 μm), and has a critical energy >15 keV. Stable X-ray performance enabled tomographic imaging of equivalent quality to that of the μCT scanner, an important confirmation of the suitability of the laser-driven source for applications. The X-ray flux achievable with this approach scales with the laser repetition rate without compromising the source size, which will allow the recording of high-resolution μCT scans in minutes.}, } @article {pmid29871772, year = {2018}, author = {Talbert, PB and Henikoff, S}, title = {Transcribing Centromeres: Noncoding RNAs and Kinetochore Assembly.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {587-599}, doi = {10.1016/j.tig.2018.05.001}, pmid = {29871772}, issn = {0168-9525}, abstract = {Chromosome segregation depends on the attachment of spindle microtubules to sites on chromosomal DNA known as centromeres, through kinetochore protein complexes. Although RNA was found in kinetochores in the 1970s, only with recent investigations has evidence emerged that loading of the centromere-specific nucleosomes that form the foundation of the kinetochore may be coupled to centromeric transcription. Centromeric transcripts are bound by several kinetochore proteins that require them for stabilization or localization. At least some centromeres have promoter activity, and many have non-B form DNA that may facilitate their transcription. Whereas other noncoding RNAs regulate gene expression or silence transposons, cotranscriptional assembly of kinetochores is a novel function for noncoding RNAs.}, } @article {pmid29871702, year = {2018}, author = {Prasanna, N and Dissanayake, HA and Constantine, GR}, title = {Sublingual nitroglycerin for early blood pressure control in hypertensive emergencies: observations from an emergency department clinical audit in Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {355}, pmid = {29871702}, issn = {1756-0500}, mesh = {Administration, Sublingual ; Aged ; Blood Pressure/*drug effects ; Blood Pressure Determination ; Clinical Audit ; *Emergencies ; Emergency Service, Hospital/statistics & numerical data ; Female ; Humans ; Hypertension/physiopathology/*prevention & control ; Infusions, Intravenous ; Male ; Middle Aged ; Nitroglycerin/administration & dosage/*pharmacology ; Sri Lanka ; Vasodilator Agents/administration & dosage/pharmacology ; }, abstract = {OBJECTIVE: Hypertensive emergencies are potentially life threatening and require prompt blood pressure control with intravenous agents. Preparation of intravenous infusions is time consuming. Usefulness of sublingual nitroglycerin in this setting is not known. We aimed to assess the benefit of sublingual nitroglycerin as a bridge to IV therapy. In a clinical audit in an emergency department, patients presenting with hypertensive emergencies requiring intravenous nitroglycerin were administered single spray of sublingual nitroglycerin awaiting commencement of intravenous infusion. Blood pressure was monitored every 5 min to observe the degree and speed of reduction.

RESULTS: Thirty-seven patients met the selection criteria. Mean age was 65.8 years (SD 7.04), and 29 were males (88.4%). Mean values of systolic, diastolic and mean blood pressures on admission were 217, 137, 163 mmHg. At 5 and 10 min after sublingual nitroglycerin, mean reduction of mean arterial blood pressure by 12.3 and 16.3% was achieved. Only 2 patients (5.4%) showed an overcorrection of blood pressure. Minimum of 15 min were required to set up a nitroglycerin intravenous infusion. Sublingual nitroglycerin spray allows rapid blood pressure control in hypertensive emergencies and is a useful bridge during the time to prepare intravenous infusion.}, } @article {pmid29871700, year = {2018}, author = {Wickramasinghe, DP and Jayarajah, U and Samarasekera, DN}, title = {Duration taken for the anal sphincter pressures to stabilize prior to anorectal manometry.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {354}, pmid = {29871700}, issn = {1756-0500}, mesh = {Adult ; Anal Canal/*physiopathology ; Female ; Humans ; Male ; Manometry/*methods ; Middle Aged ; Pressure ; Rectum/*physiopathology ; Statistics, Nonparametric ; Time Factors ; }, abstract = {OBJECTIVES: Anorectal manometry (ARM) is an integral part of evaluating the anal sphincter function. The current recommendation of waiting for 5 min (lead-in-time) prior to beginning the recording has no evidence. A prolonged procedure may reduce patient compliance.

RESULTS: We analyzed data from 100 consecutive patients who underwent 3-dimensional ARM at a single center. Their pressure studies were analyzed in consecutive 10-s segments, beginning from the time of insertion of the probe into the anal canal. We defined stabilization of the pressure as the absence of a pressure difference among two consecutive 10-s segments. The study population had 31 males. Their mean age was 33.0 years (SD-14.4). The mean time for the pressure to stabilize was 84.2 s (SD-29.5), range 17.2-203.7 s, 95th percentile 136.2 s. Eleven and one participant(s) took longer than 120 and 150 s for the pressure to stabilize, respectively. There was no correlation of sex (Mann-Whitney U test, p = 0.89) and the time to pressure stabilization. Age and the time to stabilize (Spearman rho - 0.246, p = 0.017) showed a weak negative correlation. A lead-in-time of 5 min, as recommended by present guidelines may be unnecessary. Waiting for 150 s/2½ min may be sufficient and will minimize the procedure duration.}, } @article {pmid29871699, year = {2018}, author = {Jeimy, S and Wang, JY and Richardson, L}, title = {Evaluation of virtual patient cases for teaching diagnostic and management skills in internal medicine: a mixed methods study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {357}, pmid = {29871699}, issn = {1756-0500}, mesh = {Clinical Competence/*standards ; Education, Medical/methods/standards ; Educational Measurement/methods/*standards ; Humans ; Internal Medicine/methods/*standards ; Learning ; *Patient Simulation ; Reproducibility of Results ; Surveys and Questionnaires ; Teaching ; Training Support/methods/standards ; }, abstract = {OBJECTIVE: The virtual patient (VP) is a computer program that simulates real-life clinical scenarios and allows learners to make diagnostic and therapeutic decisions in a safe environment. Although many VP cases are available, few focus on junior trainees as their target audience. In addition, there is wide variability in trainees' clinical rotation experiences, based on local practice and referral patterns, duty hour restrictions, and competing educational requirements. In order to standardize clinical exposure and improve trainees' knowledge and perceived preparedness to manage core internal medicine cases, we developed a pool of VP cases to simulate common internal medicine presentations. We used quantitative and qualitative analyses to evaluate the effectiveness of one of our VP cases among medical trainees at University of Toronto. We also evaluated the role of VP cases in integrated teaching of non-medical expert competencies.

RESULTS: Despite modest effects on knowledge acquisition, a majority of participants enjoyed using VP cases as a resource to help them prepare for and reinforce clinical experiences. Cognitive interactivity and repetitive practice were particularly appreciated by study participants. Trainees perceived VP cases as a useful resource as their learning can be customized to their actions within the case, resulting in unique learning trajectories.}, } @article {pmid29871688, year = {2018}, author = {Fondjo, CLK and Ngoupo, PAT and Ngono, L and Plantier, JC and Njouom, R}, title = {Performance evaluation of three rapid screening assays for detection of antibodies to hepatitis C virus in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {352}, pmid = {29871688}, issn = {1756-0500}, mesh = {Cameroon ; Diagnostic Tests, Routine/*methods ; Hepatitis C/*blood/diagnosis ; Hepatitis C Antibodies/*blood ; Humans ; Mass Screening/*methods ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: This study was aimed at evaluating the performance of three CE-marked rapid diagnostic tests (RDTs): Multisure-HCV, First Response® and Toyo®; for screening anti- HCV antibody using plasma samples.

RESULTS: Overall, 200 plasma samples were used. Sensibility and specificity of these RDTs range from 71 to 99 and 78 to 100% respectively. Multisure scored a sensitivity at 99% (95% CI 97-100%) and First Response reached a specificity at 90% (95% CI 85-94.9%). Further studies should be conducted to establish an algorithm using these RTDs for the detection of HCV infection in Cameroon.}, } @article {pmid29871671, year = {2018}, author = {Mekonnen, E and Workicho, A and Hussein, N and Feyera, T}, title = {Reasons and predictors for antiretroviral therapy change among HIV-infected adults at South West Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {351}, pmid = {29871671}, issn = {1756-0500}, mesh = {Adult ; Anti-HIV Agents/*therapeutic use ; *Antiretroviral Therapy, Highly Active ; Educational Status ; Ethiopia ; Female ; HIV Infections/complications/*drug therapy ; Hospitals, University ; Humans ; Male ; Retrospective Studies ; Risk Factors ; Tertiary Care Centers ; Tuberculosis/complications ; }, abstract = {OBJECTIVE: This retrospective cohort study is aimed to assess reasons and predictors of regimen change from initial highly active antiretroviral therapy among 1533 Human Immunodeficiency virus-infected adult patients at the Jimma University Tertiary Hospital.

RESULTS: One in two (47.7%) adults changed their antiretroviral therapy regimen. Patients who were above the primary level of education [Hazard ratio (HR) 1.241 (95% CI 1.070-1.440)] and with human immunodeficiency virus/tuberculosis co-infection [HR 1.405 (95% CI 1.156-1.708)] had the higher risk of regimen change than their comparator. Individuals on Efavirenz [HR 0.675 (95% CI 0.553-0.825)] and non-stavudine [HR 0.494 (95% CI 0.406-0.601)] based regimens had lower risk of regimen change.}, } @article {pmid29871669, year = {2018}, author = {Al Amer, HS and Sabbahi, MA and Alrowayeh, HN and Bryan, WJ and Olson, SL}, title = {Electromyographic activity of quadriceps muscle during sit-to-stand in patients with unilateral knee osteoarthritis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {356}, pmid = {29871669}, issn = {1756-0500}, mesh = {Aged ; Biomechanical Phenomena ; Electromyography/*methods ; Female ; Humans ; Knee Joint/physiopathology ; Male ; Middle Aged ; Osteoarthritis, Knee/*physiopathology ; Posture/*physiology ; Quadriceps Muscle/*physiopathology ; Range of Motion, Articular/physiology ; }, abstract = {OBJECTIVE: The sit-to-stand (STS) is a simple test to evaluate the functional performance of the quadriceps muscle in patients with knee osteoarthritis (OA). The aim was to evaluate the electromyographic (EMG) activity of the ipsilateral quadriceps during STS task at different seat heights and feet positions in patients with severe unilateral OA. The EMG activity was recorded in a group of eight participants with unilateral OA during the performance of STS task in four conditions: (1) knee-height seat with feet together, (2) knee-height seat with feet askew (feet side by side and heel-to-toe), (3) low-height seat (25% lower than knee-height seat) with feet together, and (4) low-height seat with feet askew.

RESULTS: There was a statistically significant difference among the four conditions in the EMG activity (p =0.004). Particularly, the EMG activity of the quadriceps was significantly higher when participants rose from the low height with their feet askew than when they rose from the knee height with their feet placed together (p =0.004) or askew (p =0.002). These results recommend considering initial feet position and seat height when evaluating the functional activity of the quadriceps in patients with unilateral OA using STS test.}, } @article {pmid29871667, year = {2018}, author = {Anabire, NG and Aryee, PA and Helegbe, GK}, title = {Hematological abnormalities in patients with malaria and typhoid in Tamale Metropolis of Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {353}, pmid = {29871667}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Anemia/epidemiology ; Comorbidity ; Cross-Sectional Studies ; Female ; Ghana/epidemiology ; Hematologic Diseases/*epidemiology ; Humans ; Leukopenia/epidemiology ; Malaria, Falciparum/*epidemiology ; Male ; Middle Aged ; Prevalence ; Thrombocytopenia/epidemiology ; Typhoid Fever/*epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Anemia, Leukopenia, and thrombocytopenia are commonly observed hematological abnormalities in malaria and typhoid patients. In this study, we evaluated the prevalence of cytopenias in patients with mono-infections of plasmodium parasites (malaria group) or salmonella bacteria (typhoid group). Full blood counts from 79 patients (age ranging from 18 to 77 years) categorized into malaria and typhoid groups at the Tamale Central Hospital were assessed.

RESULTS: Data generated were entered and analyzed using SPSS version 20 and Graphpad Prism 6. Values were observed to be significant at p < 0.05. The prevalence of cytopenias were; 29.6, 48.0% for anemia, 38.9, 12.0% for thrombocytopenia, 20.4, 12.0% for leukopenia, 13.0, 8.0% for bicytopenia and 5.6, 4.0% for pancytopenia in both malaria and typhoid groups respectively. Between the two groups of patients, thrombocytopenia was significantly associated with those in the malaria group (χ2 = 5.84, p < 0.016). No association was found between cytopenias and gender in patients in the malaria group; however, the middle aged group, 36-55 years, was significantly associated with anemia (χ2 = 12.97, p < 0.002). Cytopenias were not associated with gender, and with different age categories in patients in the typhoid group.}, } @article {pmid29871632, year = {2018}, author = {Mead, BE and Ordovas-Montanes, J and Braun, AP and Levy, LE and Bhargava, P and Szucs, MJ and Ammendolia, DA and MacMullan, MA and Yin, X and Hughes, TK and Wadsworth, MH and Ahmad, R and Rakoff-Nahoum, S and Carr, SA and Langer, R and Collins, JJ and Shalek, AK and Karp, JM}, title = {Harnessing single-cell genomics to improve the physiological fidelity of organoid-derived cell types.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {62}, pmid = {29871632}, issn = {1741-7007}, support = {R01 HL095791/HL/NHLBI NIH HHS/United States ; 1DP2OD020839/GM/NIGMS NIH HHS/United States ; 5U24AI118672//National Institute of Allergy and Infectious Diseases/International ; R01 AI138546/AI/NIAID NIH HHS/United States ; 1R33CA202820/NH/NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; 1U54CA217377/NH/NIH HHS/United States ; R01 HL095722/HL/NHLBI NIH HHS/United States ; P01 AI039671/AI/NIAID NIH HHS/United States ; R33 CA202820/CA/NCI NIH HHS/United States ; 1R01HL126554/NH/NIH HHS/United States ; R01 DE013023/DE/NIDCR NIH HHS/United States ; 1R01DA046277/NH/NIH HHS/United States ; 2R01HL095791/NH/NIH HHS/United States ; U19 AI089992/AI/NIAID NIH HHS/United States ; 2U19AI089992/NH/NIH HHS/United States ; K08 AI130392/AI/NIAID NIH HHS/United States ; U24 AI118672/AI/NIAID NIH HHS/United States ; R56 HL126554/HL/NHLBI NIH HHS/United States ; 1R01AI138546/NH/NIH HHS/United States ; RM1 HG006193/HG/NHGRI NIH HHS/United States ; U54 CA217377/CA/NCI NIH HHS/United States ; 2RM1HG006193/HG/NHGRI NIH HHS/United States ; R01 DA046277/DA/NIDA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {BACKGROUND: Single-cell genomic methods now provide unprecedented resolution for characterizing the component cell types and states of tissues such as the epithelial subsets of the gastrointestinal tract. Nevertheless, functional studies of these subsets at scale require faithful in vitro models of identified in vivo biology. While intestinal organoids have been invaluable in providing mechanistic insights in vitro, the extent to which organoid-derived cell types recapitulate their in vivo counterparts remains formally untested, with no systematic approach for improving model fidelity.

RESULTS: Here, we present a generally applicable framework that utilizes massively parallel single-cell RNA-seq to compare cell types and states found in vivo to those of in vitro models such as organoids. Furthermore, we leverage identified discrepancies to improve model fidelity. Using the Paneth cell (PC), which supports the stem cell niche and produces the largest diversity of antimicrobials in the small intestine, as an exemplar, we uncover fundamental gene expression differences in lineage-defining genes between in vivo PCs and those of the current in vitro organoid model. With this information, we nominate a molecular intervention to rationally improve the physiological fidelity of our in vitro PCs. We then perform transcriptomic, cytometric, morphologic and proteomic characterization, and demonstrate functional (antimicrobial activity, niche support) improvements in PC physiology.

CONCLUSIONS: Our systematic approach provides a simple workflow for identifying the limitations of in vitro models and enhancing their physiological fidelity. Using adult stem cell-derived PCs within intestinal organoids as a model system, we successfully benchmark organoid representation, relative to that in vivo, of a specialized cell type and use this comparison to generate a functionally improved in vitro PC population. We predict that the generation of rationally improved cellular models will facilitate mechanistic exploration of specific disease-associated genes in their respective cell types.}, } @article {pmid29871614, year = {2018}, author = {Ma, C and Jing, C and Chang, B and Yan, J and Liang, B and Liu, L and Yang, Y and Zhao, Z}, title = {The effect of promoter methylation on MdMYB1 expression determines the level of anthocyanin accumulation in skins of two non-red apple cultivars.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {108}, pmid = {29871614}, issn = {1471-2229}, support = {31471845//Natinoal Natural Science Foundation of China/ ; CARS-27//Modern Agro-industry Technology Research System, China/ ; }, mesh = {Alleles ; Anthocyanins/*metabolism ; DNA Methylation/*drug effects ; Decitabine/pharmacology ; Fruit/genetics/metabolism ; Malus/*genetics/metabolism ; Phenotype ; Pigmentation/drug effects ; Plant Proteins/genetics ; Promoter Regions, Genetic/*genetics ; RNA, Messenger ; RNA, Plant/genetics ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: Fruit color in apple (Malus domestica Borkh.) is ascribed mainly to the accumulation of anthocyanin pigments, and is an important trait for determining fruit market acceptance. Bagging is a commonly used treatment to enhance the red pigmentation in apple skin. The MdMYB1 transcription factor gene plays an important role in the biosynthesis of anthocyanin in apple after bag removal, but little is known about how MdMYB1 transcription is regulated.

RESULTS: In this study, we investigated pigmentation in the non-red skinned cultivars 'Granny Smith' and 'Golden Delicious' after bag removal. The fruit skins of the two cultivars showed red/pink pigmentation after bag treatment. Transcript levels of MdMYB1, the master regulator of anthocyanin biosynthesis in apple, increased, and showed a correlation with anthocyanin content in both cultivars after bag removal. The MdMYB1 genomic sequences were compared in the two cultivars, which showed that the green-fruited cultivar 'Granny Smith' harbors the MdMYB1-1 and MdMYB1-2 alleles, while the yellow-fruited cultivar 'Golden Delicious' harbors only MdMYB1-2. A comparison of methylation levels in the 2 kb region upstream of the MdMYB1 ATG between the bag-treated fruits after removal from the bags and the unbagged fruits showed a correlation between hypomethylation and the red-skin phenotype in 'Granny Smith'. Moreover, 'Granny Smith' fruits responded to treatment with 5-aza-2'-deoxycytidine, an inducer of DNA demethylation. An investigation of the MdMYB1 promoter in 'Granny Smith' showed reduced methylation in the regions - 2026 to - 1870 bp, - 1898 to - 1633 bp, and - 541 to - 435 bp after bag removal and 5-aza-2'-deoxycytidine treatments.

CONCLUSIONS: Differences in anthocyanin levels between 'Granny Smith' and 'Golden Delicious' can be explained by differential accumulation of MdMYB1-specific mRNA. Different levels of MdMYB1 transcripts in the two cultivars are associated with methylation levels in the promoter region. Hypomethylation of the MdMYB1 promoter is correlated with the formation of red pigmentation in 'Granny Smith' fruit skins. As a result, red pigmentation in Granny Smith' was more intense than in 'Golden Delicious' fruits after bag removal.}, } @article {pmid29871612, year = {2018}, author = {Peraldo-Neia, C and Ostano, P and Cavalloni, G and Pignochino, Y and Sangiolo, D and De Cecco, L and Marchesi, E and Ribero, D and Scarpa, A and De Rose, AM and Giuliani, A and Calise, F and Raggi, C and Invernizzi, P and Aglietta, M and Chiorino, G and Leone, F}, title = {Transcriptomic analysis and mutational status of IDH1 in paired primary-recurrent intrahepatic cholangiocarcinoma.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {440}, pmid = {29871612}, issn = {1471-2164}, support = {16:30//Associazione Italiana Ricerca sul Cancro-AIRC 5X1000 2010-Ministry of Health, FPO/ ; LEOF_RIC_LOC_14_01//Università di Torino anno 2014 -: Fondo per la ricerca locale (Linea B)/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Bile Duct Neoplasms/*genetics/pathology ; Cholangiocarcinoma/*genetics/pathology ; Disease Progression ; Epithelial-Mesenchymal Transition/genetics ; Female ; *Gene Expression Profiling ; Humans ; Isocitrate Dehydrogenase/*genetics ; Male ; Middle Aged ; *Mutation ; Recurrence ; }, abstract = {BACKGROUND: Effective target therapies for intrahepatic cholangiocarcinoma (ICC) have not been identified so far. One of the reasons may be the genetic evolution from primary (PR) to recurrent (REC) tumors. We aim to identify peculiar characteristics and to select potential targets specific for recurrent tumors. Eighteen ICC paired PR and REC tumors were collected from 5 Italian Centers. Eleven pairs were analyzed for gene expression profiling and 16 for mutational status of IDH1. For one pair, deep mutational analysis by Next Generation Sequencing was also carried out. An independent cohort of patients was used for validation.

RESULTS: Two class-paired comparison yielded 315 differentially expressed genes between REC and PR tumors. Up-regulated genes in RECs are involved in RNA/DNA processing, cell cycle, epithelial to mesenchymal transition (EMT), resistance to apoptosis, and cytoskeleton remodeling. Down-regulated genes participate to epithelial cell differentiation, proteolysis, apoptotic, immune response, and inflammatory processes. A 24 gene signature is able to discriminate RECs from PRs in an independent cohort; FANCG is statistically associated with survival in the chol-TCGA dataset. IDH1 was mutated in the RECs of five patients; 4 of them displayed the mutation only in RECs. Deep sequencing performed in one patient confirmed the IDH1 mutation in REC.

CONCLUSIONS: RECs are enriched for genes involved in EMT, resistance to apoptosis, and cytoskeleton remodeling. Key players of these pathways might be considered druggable targets in RECs. IDH1 is mutated in 30% of RECs, becoming both a marker of progression and a target for therapy.}, } @article {pmid29871610, year = {2018}, author = {Hay, EHA and Utsunomiya, YT and Xu, L and Zhou, Y and Neves, HHR and Carvalheiro, R and Bickhart, DM and Ma, L and Garcia, JF and Liu, GE}, title = {Genomic predictions combining SNP markers and copy number variations in Nellore cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {441}, pmid = {29871610}, issn = {1471-2164}, support = {2011-67015-30183//National Institute of Food and Agriculture/ ; 2013-67015-20951//National Institute of Food and Agriculture/ ; US-4997-17//United States - Israel Binational Agricultural Research and Development Fund/ ; }, mesh = {Animals ; Cattle/*genetics ; DNA Copy Number Variations/*genetics ; Genetic Markers/genetics ; *Genomics ; Genotyping Techniques ; Phenotype ; Polymorphism, Single Nucleotide/*genetics ; Quality Control ; }, abstract = {BACKGROUND: Due to the advancement in high throughput technology, single nucleotide polymorphism (SNP) is routinely being incorporated along with phenotypic information into genetic evaluation. However, this approach often cannot achieve high accuracy for some complex traits. It is possible that SNP markers are not sufficient to predict these traits due to the missing heritability caused by other genetic variations such as microsatellite and copy number variation (CNV), which have been shown to affect disease and complex traits in humans and other species.

RESULTS: In this study, CNVs were included in a SNP based genomic selection framework. A Nellore cattle dataset consisting of 2230 animals genotyped on BovineHD SNP array was used, and 9 weight and carcass traits were analyzed. A total of six models were implemented and compared based on their prediction accuracy. For comparison, three models including only SNPs were implemented: 1) BayesA model, 2) Bayesian mixture model (BayesB), and 3) a GBLUP model without polygenic effects. The other three models incorporating both SNP and CNV included 4) a Bayesian model similar to BayesA (BayesA+CNV), 5) a Bayesian mixture model (BayesB+CNV), and 6) GBLUP with CNVs modeled as a covariable (GBLUP+CNV). Prediction accuracies were assessed based on Pearson's correlation between de-regressed EBVs (dEBVs) and direct genomic values (DGVs) in the validation dataset. For BayesA, BayesB and GBLUP, accuracy ranged from 0.12 to 0.62 across the nine traits. A minimal increase in prediction accuracy for some traits was noticed when including CNVs in the model (BayesA+CNV, BayesB+CNV, GBLUP+CNV).

CONCLUSIONS: This study presents the first genomic prediction study integrating CNVs and SNPs in livestock. Combining CNV and SNP marker information proved to be beneficial for genomic prediction of some traits in Nellore cattle.}, } @article {pmid29871605, year = {2018}, author = {Selvakumar, G and Shagol, CC and Kim, K and Han, S and Sa, T}, title = {Spore associated bacteria regulates maize root K+/Na+ ion homeostasis to promote salinity tolerance during arbuscular mycorrhizal symbiosis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {109}, pmid = {29871605}, issn = {1471-2229}, support = {2015R1A2A1A05001885//National Research Foundation of Korea/ ; }, mesh = {Bacteria/*metabolism ; Cell Wall/metabolism ; Green Fluorescent Proteins ; *Homeostasis ; Ion Transport ; Membrane Transport Proteins/genetics/metabolism ; Mycorrhizae/*physiology ; Plant Proteins/genetics/metabolism ; Plant Roots/microbiology/physiology ; Potassium/*metabolism ; Salt Tolerance ; Seedlings/microbiology/physiology ; Sodium/*metabolism ; Sodium Chloride/metabolism ; Spores, Fungal ; Stress, Physiological ; Symbiosis ; Zea mays/*microbiology/physiology ; }, abstract = {BACKGROUND: The interaction between arbuscular mycorrhizal fungi (AMF) and AMF spore associated bacteria (SAB) were previously found to improve mycorrhizal symbiotic efficiency under saline stress, however, the information about the molecular basis of this interaction remain unknown. Therefore, the present study aimed to investigate the response of maize plants to co-inoculation of AMF and SAB under salinity stress.

RESULTS: The co-inoculation of AMF and SAB significantly improved plant dry weight, nutrient content of shoot and root tissues under 25 or 50 mM NaCl. Importantly, co-inoculation significantly reduced the accumulation of proline in shoots and Na+ in roots. Co-inoculated maize plants also exhibited high K+/Na+ ratios in roots at 25 mM NaCl concentration. Mycorrhizal colonization significantly positively altered the expression of ZmAKT2, ZmSOS1, and ZmSKOR genes, to maintain K+ and Na+ ion homeostasis. Confocal laser scanning microscope (CLSM) view showed that SAB were able to move and localize into inter- and intracellular spaces of maize roots and were closely associated with the spore outer hyaline layer.

CONCLUSION: These new findings indicate that co-inoculation of AMF and SAB effectively alleviates the detrimental effects of salinity through regulation of SOS pathway gene expression and K+/Na+ homeostasis to improve maize plant growth.}, } @article {pmid29871599, year = {2018}, author = {Yang, M and Zhang, C and Zhang, MZ and Zhang, S}, title = {Beta-defensin derived cationic antimicrobial peptides with potent killing activity against gram negative and gram positive bacteria.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {54}, pmid = {29871599}, issn = {1471-2180}, abstract = {BACKGROUND: Avian β-defensins (AvBD) are cationic antimicrobial peptides (CAMP) with broad-spectrum antimicrobial activity, chemotactic property, and low host cytotoxicity. However, their bactericidal activity is greatly compromised under physiological salt concentrations which limits the use of these peptides as therapeutic agents. The length and the complex structure involving three conserved disulfide bridges are additional drawbacks associated with high production cost. In the present study, short linear CAMPs (11 to 25 a.a. residues) were developed based on the key functional components of AvBDs with additional modifications. Their biological functions were characterized.

RESULTS: CAMP-t1 contained the CCR2 binding domain (N-terminal loop and adjacent α-helix) of AvBD-12 whereas CAMP-t2 comprised the key a.a. residues responsible for the concentrated positive surface charge and hydrophobicity of AvBD-6. Both CAMP-t1 and CAMP-t2 demonstrated strong antimicrobial activity against Pseudomonas aeruginosa, Staphylococcus aureus and Staphylococcus pseudintermedius. However, CAMP-t1 failed to show chemotactic activity and CAMP-t2, although superior in killing Staphylococcus spp., remained sensitive to salts. Using an integrated design approach, CAMP-t2 was further modified to yield CAMP-A and CAMP-B which possessed the following characteristics: α-helical structure with positively and negatively charged residues aligned on the opposite side of the helix, lack of protease cutting sites, C-terminal poly-Trp tail, N-terminal acetylation, and C-terminal amidation. Both CAMP-A and CAMP-B demonstrated strong antimicrobial activity against multidrug-resistant P. aeruginosa and methicillin-resistant S. pseudintermedius (MRSP) strains. These peptides were resistant to major proteases and fully active at physiological concentrations of NaCl and CaCl2. The peptides were minimally cytotoxic to avian and murine cells and their therapeutic index was moderate (≥ 4.5).

CONCLUSIONS: An integrated design approach can be used to develop short and potent antimicrobial peptides, such as CAMP-A and CAMP-B. The advantageous characteristics, including structural simplicity, resistance to salts and proteases, potent antimicrobial activity, rapid membrane attacking mode, and moderate therapeutic index, suggest that CAMP-A and CAMP-B are excellent candidates for development as therapeutic agents against multidrug-resistant P. aeruginosa and methicillin-resistant staphylococci.}, } @article {pmid29871594, year = {2018}, author = {Xi, J and Wang, M and Li, A}, title = {Discovering mutated driver genes through a robust and sparse co-regularized matrix factorization framework with prior information from mRNA expression patterns and interaction network.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {214}, pmid = {29871594}, issn = {1471-2105}, abstract = {BACKGROUND: Discovery of mutated driver genes is one of the primary objective for studying tumorigenesis. To discover some relatively low frequently mutated driver genes from somatic mutation data, many existing methods incorporate interaction network as prior information. However, the prior information of mRNA expression patterns are not exploited by these existing network-based methods, which is also proven to be highly informative of cancer progressions.

RESULTS: To incorporate prior information from both interaction network and mRNA expressions, we propose a robust and sparse co-regularized nonnegative matrix factorization to discover driver genes from mutation data. Furthermore, our framework also conducts Frobenius norm regularization to overcome overfitting issue. Sparsity-inducing penalty is employed to obtain sparse scores in gene representations, of which the top scored genes are selected as driver candidates. Evaluation experiments by known benchmarking genes indicate that the performance of our method benefits from the two type of prior information. Our method also outperforms the existing network-based methods, and detect some driver genes that are not predicted by the competing methods.

CONCLUSIONS: In summary, our proposed method can improve the performance of driver gene discovery by effectively incorporating prior information from interaction network and mRNA expression patterns into a robust and sparse co-regularized matrix factorization framework.}, } @article {pmid29871590, year = {2018}, author = {Su, L and Liu, G and Bai, T and Meng, X and Ma, Q}, title = {MGOGP: a gene module-based heuristic algorithm for cancer-related gene prioritization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {215}, pmid = {29871590}, issn = {1471-2105}, abstract = {BACKGROUND: Prioritizing genes according to their associations with a cancer allows researchers to explore genes in more informed ways. By far, Gene-centric or network-centric gene prioritization methods are predominated. Genes and their protein products carry out cellular processes in the context of functional modules. Dysfunctional gene modules have been previously reported to have associations with cancer. However, gene module information has seldom been considered in cancer-related gene prioritization.

RESULTS: In this study, we propose a novel method, MGOGP (Module and Gene Ontology-based Gene Prioritization), for cancer-related gene prioritization. Different from other methods, MGOGP ranks genes considering information of both individual genes and their affiliated modules, and utilize Gene Ontology (GO) based fuzzy measure value as well as known cancer-related genes as heuristics. The performance of the proposed method is comprehensively validated by using both breast cancer and prostate cancer datasets, and by comparison with other methods. Results show that MGOGP outperforms other methods, and successfully prioritizes more genes with literature confirmed evidence.

CONCLUSIONS: This work will aid researchers in the understanding of the genetic architecture of complex diseases, and improve the accuracy of diagnosis and the effectiveness of therapy.}, } @article {pmid29871589, year = {2018}, author = {Haynsen, MS and Vatanparast, M and Mahadwar, G and Zhu, D and Moger-Reischer, RZ and Doyle, JJ and Crandall, KA and Egan, AN}, title = {De novo transcriptome assembly of Pueraria montana var. lobata and Neustanthus phaseoloides for the development of eSSR and SNP markers: narrowing the US origin(s) of the invasive kudzu.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {439}, pmid = {29871589}, issn = {1471-2164}, support = {DEB-1352217//Division of Environmental Biology/ ; DEB-0948800//Division of Environmental Biology/ ; }, mesh = {*Gene Expression Profiling ; *Introduced Species ; Microsatellite Repeats/*genetics ; Molecular Sequence Annotation ; Polymorphism, Single Nucleotide ; Pueraria/*genetics/*growth & development ; Quality Control ; Sequence Analysis ; }, abstract = {BACKGROUND: Kudzu, Pueraria montana var. lobata, is a woody vine native to Southeast Asia that has been introduced globally for cattle forage and erosion control. The vine is highly invasive in its introduced areas, including the southeastern US. Modern molecular marker resources are limited for the species, despite its importance. Transcriptomes for P. montana var. lobata and a second phaseoloid legume taxon previously ascribed to genus Pueraria, Neustanthus phaseoloides, were generated and mined for microsatellites and single nucleotide polymorphisms.

RESULTS: Roche 454 sequencing of P. montana var. lobata and N. phaseoloides transcriptomes produced read numbers ranging from ~ 280,000 to ~ 420,000. Trinity assemblies produced an average of 17,491 contigs with mean lengths ranging from 639 bp to 994 bp. Transcriptome completeness, according to BUSCO, ranged between 64 and 77%. After vetting for primer design, there were 1646 expressed simple sequence repeats (eSSRs) identified in P. montana var. lobata and 1459 in N. phaseoloides. From these eSSRs, 17 identical primer pairs, representing inter-generic phaseoloid eSSRs, were created. Additionally, 13 primer pairs specific to P. montana var. lobata were also created. From these 30 primer pairs, a final set of seven primer pairs were used on 68 individuals of P. montana var. lobata for characterization across the US, China, and Japan. The populations exhibited from 20 to 43 alleles across the seven loci. We also conducted pairwise tests for high-confidence SNP discovery from the kudzu transcriptomes we sequenced and two previously sequenced P. montana var. lobata transcriptomes. Pairwise comparisons between P. montana var. lobata ranged from 358 to 24,475 SNPs, while comparisons between P. montana var. lobata and N. phaseoloides ranged from 5185 to 30,143 SNPs.

CONCLUSIONS: The discovered molecular markers for kudzu provide a starting point for comparative genetic studies within phaseoloid legumes. This study both adds to the current genetic resources and presents the first available genomic resources for the invasive kudzu vine. Additionally, this study is the first to provide molecular evidence to support the hypothesis of Japan as a source of US kudzu and begins to narrow the origin of US kudzu to the central Japanese island of Honshu.}, } @article {pmid29871588, year = {2018}, author = {Lee, J and Lee, D and Sim, M and Kwon, D and Kim, J and Ko, Y and Kim, J}, title = {mySyntenyPortal: an application package to construct websites for synteny block analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {216}, pmid = {29871588}, issn = {1471-2105}, support = {P30 CA072720/CA/NCI NIH HHS/United States ; S10 OD012346/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: Advances in sequencing technologies have facilitated large-scale comparative genomics based on whole genome sequencing. Constructing and investigating conserved genomic regions among multiple species (called synteny blocks) are essential in the comparative genomics. However, they require significant amounts of computational resources and time in addition to bioinformatics skills. Many web interfaces have been developed to make such tasks easier. However, these web interfaces cannot be customized for users who want to use their own set of genome sequences or definition of synteny blocks.

RESULTS: To resolve this limitation, we present mySyntenyPortal, a stand-alone application package to construct websites for synteny block analyses by using users' own genome data. mySyntenyPortal provides both command line and web-based interfaces to build and manage websites for large-scale comparative genomic analyses. The websites can be also easily published and accessed by other users. To demonstrate the usability of mySyntenyPortal, we present an example study for building websites to compare genomes of three mammalian species (human, mouse, and cow) and show how they can be easily utilized to identify potential genes affected by genome rearrangements.

CONCLUSIONS: mySyntenyPortal will contribute for extended comparative genomic analyses based on large-scale whole genome sequences by providing unique functionality to support the easy creation of interactive websites for synteny block analyses from user's own genome data.}, } @article {pmid29870859, year = {2018}, author = {Bolstad, KSR and Braid, HE and Strugnell, JM and Lindgren, AR and Lischka, A and Kubodera, T and Laptikhovsky, VL and Roura Labiaga, A}, title = {A mitochondrial phylogeny of the family Onychoteuthidae (Cephalopoda: Oegopsida).}, journal = {Molecular phylogenetics and evolution}, volume = {128}, number = {}, pages = {88-97}, doi = {10.1016/j.ympev.2018.05.032}, pmid = {29870859}, issn = {1095-9513}, abstract = {The oegopsid squid family Onychoteuthidae was recently revised based on morphology, but sufficient material for a complementary molecular analysis has not been available until now. In the present study, over 250 sequences of cytochrome c oxidase subunit I (COI) and 16S rRNA for 222 individuals were analysed to create a combined phylogeny for the family. Results support monophyly for the family and all seven onychoteuthid genera (including Moroteuthopsis, established herein as the senior genus name for species formerly attributed to Kondakovia); 29 genetically distinct species were recovered, with the BIN (Barcode Index Number) analysis for COI showing good congruence overall with morphological species groupings. No sequences were available for five additional known species, making the total family diversity likely to exceed 34 species. Seven of the BINs formed in this study appear to represent undescribed taxa, suggesting that even in this relatively well-studied family, much additional work remains before a comprehensive understanding of the diversity and evolutionary relationships for the Onychoteuthidae can be achieved.}, } @article {pmid29870858, year = {2018}, author = {Nauheimer, L and Schley, RJ and Clements, MA and Micheneau, C and Nargar, K}, title = {Australasian orchid biogeography at continental scale: Molecular phylogenetic insights from the Sun Orchids (Thelymitra, Orchidaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {304-319}, doi = {10.1016/j.ympev.2018.05.031}, pmid = {29870858}, issn = {1095-9513}, abstract = {Australia harbours a rich and highly endemic orchid flora, with c. 90% of species endemic to the country. Despite that, the biogeographic history of Australasian orchid lineages is only poorly understood. Here we examined evolutionary relationships and the spatio-temporal evolution of the sun orchids (Thelymitra, 119 species), which display disjunct distribution patterns frequently found in Australasian orchid lineages. Phylogenetic analyses were conducted based on one nuclear (ITS) and three plastid markers (matK, psbJ-petA, ycf1) using Maximum Likelihood and Bayesian inference. Divergence time estimations were carried out with a relaxed molecular clock in a Bayesian framework. Ancestral ranges were estimated using the dispersal-extinction-cladogenesis model and an area coding based on major disjunctions. The phylogenetic analyses clarified intergeneric relationships within Thelymitrinae, with Epiblema being sister to Thelymitra plus Calochilus, both of which were well-supported. Within Thelymitra, eight major and several minor clades were retrieved in the nuclear and plastid phylogenetic reconstructions. Five major clades corresponded to species complexes previously recognized based on morphological characters, whereas other previously recognized species groups were found to be paraphyletic. Conflicting signals between the nuclear and plastid phylogenetic reconstructions provided support for hybridization and plastid capture events both in the deeper evolutionary history of the genus and more recently. Divergence time estimation placed the origin of Thelymitra in the late Miocene (c. 10.8 Ma) and the origin of the majority of the main clades within Thelymitra during the late Pliocene and early Pleistocene, with the majority of extant species arising during the Pleistocene. Ancestral range reconstruction revealed that the early diversification of the genus in the late Miocene and Pliocene took place predominantly in southwest Australia, where most species with highly restricted distributional ranges occur. Several long-distance dispersal events eastwards across the Nullarbor Plain were inferred, recurrently resulting in lineage divergence within the genus. The predominant eastwards direction of long-distance dispersal events in Thelymitra highlights the importance of the prevailing westerly winds in the Southern Hemisphere for the present-day distribution of the genus, giving rise to the Thelymitra floras of Tasmania, New Zealand and New Caledonia, which were inferred to be of comparatively recent origin.}, } @article {pmid29870857, year = {2018}, author = {Freitas, ES and Bauer, AM and Siler, CD and Broadley, DG and Jackman, TR}, title = {Phylogenetic and morphological investigation of the Mochlus afer-sundevallii species complex (Squamata: Scincidae) across the arid corridor of sub-Saharan Africa.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {280-287}, doi = {10.1016/j.ympev.2018.04.020}, pmid = {29870857}, issn = {1095-9513}, abstract = {The aridification of Africa resulted in the fragmentation of forests and the expansion of an arid corridor stretching from the northeast to southwest portion of sub-Saharan Africa, but the role this corridor has had in species-level diversification of southern African vertebrates is poorly understood. The skink species Mochlus afer and M. sundevallii inhabit wide areas of the arid corridor and are therefore an ideal species pair for studying patterns of genetic and phenotypic diversity associated with this landscape. However, species boundaries between these taxa have been controversial. Using multi-locus molecular and morphological datasets, we investigate diversification patterns of the M. afer-sundevallii Species Complex across the arid corridor. Although analyses of genetic data reveals some genetic structure among geographic populations, results of phylogenetic and morphological analyses provide little support for two distinct evolutionary lineages, suggesting that populations previously referred to as M. afer and M. sundevallii represent a single species, Mochlus sundevallii. Genetic diversity is unequally distributed across the arid corridor, with observed patterns consistent with aridification-facilitated diversification southward across southern Africa. Additional geographic and population-level sampling is necessary before more conclusive inferences can be drawn about the role historical climate transitions have played in skink diversification patterns across southern Africa.}, } @article {pmid29870691, year = {2018}, author = {Ahmed-de-Prado, S and Diaz-Garcia, S and Baonza, A}, title = {JNK and JAK/STAT signalling are required for inducing loss of cell fate specification during imaginal wing discs regeneration in Drosophila melanogaster.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {31-41}, doi = {10.1016/j.ydbio.2018.05.021}, pmid = {29870691}, issn = {1095-564X}, mesh = {Animals ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Imaginal Discs/*physiology ; MAP Kinase Kinase 4/genetics/*metabolism ; Regeneration/*physiology ; STAT Transcription Factors/genetics/*metabolism ; Signal Transduction/*physiology ; Wings, Animal/*embryology ; }, abstract = {The regenerative process after tissue damage relies on a variety of cellular responses that includes compensatory cell proliferation and cell fate re-specification. The identification of the signalling networks regulating these cellular events is a central question in regenerative biology. Tissue regeneration models in Drosophila have shown that two of the signals that play a fundamental role during the early stages of regeneration are the c-Jun N-terminal kinase (JNK) and JAK/STAT signalling pathways. These pathways have been shown to be required for controlling regenerative proliferation, however their contribution to the processes of cellular reprogramming and cell fate re-specification that take place during regeneration are largely unknown. Here, we present evidence for a previously unrecognised function of the cooperative activities of JNK and JAK/STAT signalling pathways in inducing loss of cell fate specification in imaginal discs. We show that co-activation of these signalling pathways induces both the cell fate changes in injured areas, as well as in adjacent cells. We have also found that this function relies on the activity of the Caspase initiator encoded by the gene dronc.}, } @article {pmid29869980, year = {2018}, author = {Mohammadipanah, F and Atasayar, E and Heidarian, S and Wink, J}, title = {Glycomyces sediminimaris sp. nov., a new species of actinobacteria isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2357-2363}, doi = {10.1099/ijsem.0.002847}, pmid = {29869980}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Iran ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Streptomyces/classification ; Vitamin K 2/chemistry ; }, abstract = {A novel Glycomyces strain, designated as MH2460T, was isolated from marine sediment collected from 12 m depth in Rostami seaport, Bushehr Province in Iran. On International Streptomyces Project 2 medium it produced branching substrate hyphae that developed into a large number of irregularly shaped spores in 8 days. It showed optimal growth at 25-35 °C, pH 6.0-8.0 and in salinity between 2.5-5 % (w/v) NaCl. Chemotaxonomic and molecular characteristics of the isolate matched descriptions for members of the genus Glycomyces. Whole-cell hydrolysates of strain MH2460T contained meso-diaminopimelic acids along with glucose, ribose and small traces of xylose and galactose. The phospholipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannosides as well as two unidentified phosphoglycolipids, one unidentified phospholipid and an unidentified aminolipid. The predominant menaquinones were MK-11(H4) and MK-10(H4). The fatty-acid pattern was mainly composed of anteiso-C15 : 0, anteiso-C17 : 0, iso-C15 : 0 and iso-C16 : 0. The strain belongs to the genus Glycomyces based on 16S rRNA gene sequence with the highest pairwise sequence identity (98.3 %) with Glycomyces phytohabitans KLBMP 1483T. The DNA-DNA hybridization value showed 53.9±2.7 % identity when MH2460T was compared to this reference strain. The G+C content of the DNA was 70.2 mol%. Based on phenotypic, biochemical, chemotaxonomic and genotypic features, strain MH2460T (DSM 103727T=UTMC 2460T=NCCB 100631T) is considered to represent a novel species of the genus Glycomyces, for which the name Glycomyces sediminimaris is proposed.}, } @article {pmid29869978, year = {2018}, author = {Wang, J and Leiva, S and Huang, J and Huang, Y}, title = {Amycolatopsis antarctica sp. nov., isolated from the surface of an Antarctic brown macroalga.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2348-2356}, doi = {10.1099/ijsem.0.002844}, pmid = {29869978}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Actinomycetales/classification ; Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Phaeophyta/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seaweed/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Two moderately psychrophilic actinobacterial strains, designated AU-G6T and AU-A3.2, isolated from the surface of an Antarctic macroalga, Adenocystis utricularis (Bory) Skottsberg, was taxonomically characterized based on a polyphasic investigation. The two strains had nearly identical 16S rRNA gene sequences and formed a distinct phyletic line within the genus Amycolatopsis of the family Pseudonocardiaceae. They were phylogenetically close to Amycolatopsis nigrescens JCM 14717T, Amycolatopsis minnesotensis JCM 14545T and Amycolatopsis magusensis DSM 45510T, with 16S rRNA gene sequence similarities of 97.77, 97.20 and 97.19 %, respectively. Phylogenomic analysis based on the whole genome data supported that strain AU-G6T was distantly related to the Amycolatopsis species. The isolates shared a range of phenotypic markers typical of members of the genus Amycolatopsis, but also had a range of cultural, physiological and biochemical characteristics that separated them from related Amycolatopsis species. The isolates showed growth only in media supplemented with salt, indicating their marine origin. The cell wall of the isolates contained meso-diaminopimelic acid, and arabinose and galactose were detected as diagnostic sugars (type IV). The main menaquinone was MK-9(H4). The main polar lipids were phosphatidylethanolamine, hydroxy-phosphotidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol (type II). The fatty acid type was 3c. The combined genotypic and phenotypic data indicated that the two isolates represent a novel species of the genus Amycolatopsis. The name proposed for this species is Amycolatopsis antarctica sp. nov., with type strain AU-G6T (=CGMCC 4.7351T=NBRC 112404T).}, } @article {pmid29869977, year = {2018}, author = {Genuário, DB and de Souza, WR and Monteiro, RTR and Sant Anna, CL and Melo, IS}, title = {Amazoninema gen. nov., (Synechococcales, Pseudanabaenaceae) a novel cyanobacteria genus from Brazilian Amazonian rivers.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2249-2257}, doi = {10.1099/ijsem.0.002821}, pmid = {29869977}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Brazil ; Cyanobacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Ribosomal Spacer/genetics ; Genes, Bacterial ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; }, abstract = {The genus Leptolyngbya includes morphotypes with thin cells and simple morphology, and is one of the most common cyanobacterial genera found in a wide range of environments. In many cases, however, the morphotypes assigned to this genus do not share a common ancestor based on 16S rRNA gene phylogeny, which has led to the description of novel genera, such as Nodosilinea, Oculatella, Pantanalinema, Alkalinema, Thermoleptolyngbya, Onodrimia, Timaviella and Toxifilum. Thus, four novel isolates, with a comparable morphology to Leptolyngbya, were recovered from the Amazon and Solimões rivers. The novel 16S rRNA gene sequences obtained from these strains were placed together as a new and distinct phylogenetic lineage that is more closely related to the clusters embracing the genera Nodosilinea, Haloleptolyngbya and Halomicronema than to the genus Leptolyngbya. Additionally, these novel 16S rRNA gene sequences showed similarity values lower than 95 % compared with those from the most phylogenetic related groups and/or established genera. Altogether, these results supported the erection of a novel genus, named Amazoninema, to accommodate the novel isolates. Likewise, a comparison of their 16S rRNA gene sequences revealed similarities higher than 99.8 %, indicating that they belong to a single species, which was corroborated by analysing their 16S-23S internal transcribed spacer regions and unique Box-B helix pattern. Few studies have been undertaken to uncover the cultured diversity of cyanobacteria from Amazonia, and to our knowledge, this is the first cyanobacteria genus erected, considering morphotypes isolated exclusively from Brazilian Amazonian rivers.}, } @article {pmid29869679, year = {2018}, author = {Wang, F and Zhao, H and Xiang, H and Wu, L and Men, X and Qi, C and Chen, G and Zhang, H and Wang, Y and Xian, M}, title = {Species Diversity and Functional Prediction of Surface Bacterial Communities on Aging Flue-Cured Tobaccos.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1306-1315}, pmid = {29869679}, issn = {1432-0991}, support = {ZDYF2017155//Hainan's Key Project of Research and Development Plan/ ; TSPD20150210//Taishan Scholars Climbing Program of Shandong/ ; 2017252//Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; }, mesh = {Bacteria/classification/genetics/*isolation & purification ; *Biodiversity ; DNA, Bacterial/genetics ; Microbiota ; Phylogeny ; Plant Leaves/chemistry/microbiology ; RNA, Ribosomal, 16S/genetics ; Tobacco/chemistry/*microbiology ; }, abstract = {Microbes on aging flue-cured tobaccos (ATFs) improve the aroma and other qualities desirable in products. Understanding the relevant organisms would picture microbial community diversity, metabolic potential, and their applications. However, limited efforts have been made on characterizing the microbial quality and functional profiling. Herein, we present our investigation of the bacterial diversity and predicted potential genetic capability of the bacteria from two AFTs using 16S rRNA gene sequences and phylogenetic investigation of communities by reconstruction of unobserved states (PICRUSt) software. The results show that dominant bacteria from AFT surfaces were classified into 48 genera, 36 families, and 7 phyla. In addition, Bacillus spp. was found prevalent on both ATFs. Furthermore, PICRUSt predictions of bacterial community functions revealed many attractive metabolic capacities in the AFT microbiota, including several involved in the biosynthesis of flavors and fragrances and the degradation of harmful compounds, such as nicotine and nitrite. These results provide insights into the importance of AFT bacteria in determining product qualities and indicate specific microbial species with predicted enzymatic capabilities for the production of high-efficiency flavors, the degradation of undesirable compounds, and the provision of nicotine and nitrite tolerance which suggest fruitful areas of investigation into the manipulation of AFT microbiota for AFT and other product improvements.}, } @article {pmid29869678, year = {2018}, author = {Mobasheri, N and Karimi, M and Hamedi, J}, title = {Implementing Electric Potential Difference as a New Practical Parameter for Rapid and Specific Measurement of Minimum Inhibitory Concentration of Antibiotics.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1290-1298}, pmid = {29869678}, issn = {1432-0991}, support = {Grant No. 93027010//Iran National Science Foundation/ ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/chemistry/*drug effects/growth & development ; Microbial Sensitivity Tests/instrumentation/*methods ; }, abstract = {New methods to determine antimicrobial susceptibility of bacterial pathogens especially the minimum inhibitory concentration (MIC) of antibiotics have great importance in pharmaceutical industry and treatment procedures. In the present study, the MIC of several antibiotics was determined against some pathogenic bacteria using macrodilution test. In order to accelerate and increase the efficiency of culture-based method to determine antimicrobial susceptibility, the possible relationship between the changes in some physico-chemical parameters including conductivity, electrical potential difference (EPD), pH and total number of test strains was investigated during the logarithmic phase of bacterial growth in presence of antibiotics. The correlation between changes in these physico-chemical parameters and growth of bacteria was statistically evaluated using linear and non-linear regression models. Finally, the calculated MIC values in new proposed method were compared with the MIC derived from macrodilution test. The results represent significant association between the changes in EPD and pH values and growth of the tested bacteria during the exponential phase of bacterial growth. It has been assumed that the proliferation of bacteria can cause the significant changes in EPD values. The MIC values in both conventional and new method were consistent to each other. In conclusion, cost and time effective antimicrobial susceptibility test can be developed based on monitoring the changes in EPD values. The new proposed strategy also can be used in high throughput screening of biocompounds for their antimicrobial activity in a relatively shorter time (6-8 h) in comparison with the conventional methods.}, } @article {pmid29869093, year = {2018}, author = {Vu, HT and Nguyen, DT and Nguyen, HQ and Chu, HH and Chu, SK and Chau, MV and Phi, QT}, title = {Antimicrobial and Cytotoxic Properties of Bioactive Metabolites Produced by Streptomyces cavourensis YBQ59 Isolated from Cinnamomum cassia Prels in Yen Bai Province of Vietnam.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1247-1255}, pmid = {29869093}, issn = {1432-0991}, support = {VAST04.07/16-17//Vietnam Academy of Science and Technology/ ; }, mesh = {Anti-Bacterial Agents/chemistry/metabolism/*pharmacology ; Cell Line, Tumor ; Cell Survival/drug effects ; Cinnamomum aromaticum/*microbiology ; Humans ; Methicillin-Resistant Staphylococcus aureus/drug effects/growth & development ; Microbial Sensitivity Tests ; Phylogeny ; Streptomyces/*chemistry/classification/genetics/*isolation & purification ; Vietnam ; }, abstract = {The endophytic actinomycete strain YBQ59 was isolated from Cinnamomum cassia Prels in Yen Bai province (21°53'14″N; 104°35'9″E) of northern Vietnam. Based on analysis of morphological, physiological characteristics and 16S rRNA gene sequence (GenBank Acc. No. MF950891), the strain YBQ59 possessed high similarity to Streptomyces cavourensis subsp. cavourensis strain NRRL 2740, therefore assigned as S. cavourensis YBQ59. The ethyl acetate extract of the YBQ59 culture broth isolated eight pure secondary metabolites, identified as 1-monolinolein (1), bafilomycin D (2), nonactic acid (3), daidzein (4), 3'-hydroxydaidzein (5), 5,11-epoxy-10-cadinanol (6), prelactone B (7), and daucosterol (8). Compounds 1, 3-8 were reported for the first time from S. cavourensis. Compounds 1-5 exhibited antimicrobial activities against both methicillin-resistant Staphylococcus aureus ATCC 33591 (MRSA) and methicillin-resistant Staphylococcus epidermidis ATCC 35984 (MRSE) among which the compound 1 revealed the strongest effects with minimum inhibitory concentrations of 8.5 and 14.6 µg/mL, respectively. The compound 2 showed high potential effect against MRSA (MIC of 11.1 µg/mL) but less effect against MRSE (MIC of 30.3 µg/mL). The cytotoxicity of the compounds 1-7 was investigated against human lung adenocarcinoma EGFR-TKI-resistant cells, among which compounds 1, 2, and 5 exhibited the strong effect against A549 cells with IC50 values of 3.6, 6.7, and 7.8 µM, respectively. Taken together, the experimental findings in this study suggested that the compounds 1 and 2 could be reproducible metabolites applicable for inhibition of both drug-resistant bacteria and cancer cell lines.}, } @article {pmid29868789, year = {2018}, author = {Bakermans, C}, title = {Adaptations to marine versus terrestrial low temperature environments as revealed by comparative genomic analyses of the genus Psychrobacter.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy102}, pmid = {29868789}, issn = {1574-6941}, abstract = {While cold-adapted bacteria isolated from marine or terrestrial low temperature environments share many similarities, cold-adapted bacteria from terrestrial environments usually grow over a broader range of temperatures suggesting different constraints of these two low temperature environments. The diversity of habitats from which Psychrobacter have been isolated (e.g. cold marine environments, frozen soils, permafrost and humans) provides a unique opportunity to examine habitat specific adaptations while reducing phylogenetic effects. Here, comparative genomic analyses of 26 strains of Psychrobacter revealed several clusters with characteristics that correlated with habitat. Marine and terrestrial Psychrobacter have amino acid composition typical of psychrophiles (e.g. fewer proline and lysine, more acidic) when compared to Psychrobacter strains associated with warm hosts, and have many potentially cold-adapted core genes (e.g. ClpX, DsbC, GroEL/GroES and MutS2). Marine and terrestrial Psychrobacter share many genes (e.g. FadB) not found in warm host Psychrobacter, which had their own distinct gene content (e.g. collagenase-like protease). Furthermore, terrestrial Psychrobacter were differentiated from marine Psychrobacter by the use of different cold adaptations and more hydrophobic and aliphatic proteins. These data suggest that terrestrial and marine Psychrobacter evolved from a mesophilic ancestor and are accumulating adaptations for low temperatures as well as for their respective habitats.}, } @article {pmid29867254, year = {2018}, author = {Wiggins, A and Bonney, R and LeBuhn, G and Parrish, JK and Weltzin, JF}, title = {A Science Products Inventory for Citizen-Science Planning and Evaluation.}, journal = {Bioscience}, volume = {68}, number = {6}, pages = {436-444}, pmid = {29867254}, issn = {0006-3568}, abstract = {Citizen science involves a range of practices involving public participation in scientific knowledge production, but outcomes evaluation is complicated by the diversity of the goals and forms of citizen science. Publications and citations are not adequate metrics to describe citizen-science productivity. We address this gap by contributing a science products inventory (SPI) tool, iteratively developed through an expert panel and case studies, intended to support general-purpose planning and evaluation of citizen-science projects with respect to science productivity. The SPI includes a collection of items for tracking the production of science outputs and data practices, which are described and illustrated with examples. Several opportunities for further development of the initial inventory are highlighted, as well as potential for using the inventory as a tool to guide project management, funding, and research on citizen science.}, } @article {pmid29867253, year = {2018}, author = {Wiggins, A and Bonney, R and LeBuhn, G and Parrish, JK and Weltzin, JF}, title = {A Science Products Inventory for Citizen-Science Planning and Evaluation.}, journal = {Bioscience}, volume = {68}, number = {6}, pages = {436-444}, pmid = {29867253}, issn = {0006-3568}, abstract = {Citizen science involves a range of practices involving public participation in scientific knowledge production, but outcomes evaluation is complicated by the diversity of the goals and forms of citizen science. Publications and citations are not adequate metrics to describe citizen-science productivity. We address this gap by contributing a science products inventory (SPI) tool, iteratively developed through an expert panel and case studies, intended to support general-purpose planning and evaluation of citizen-science projects with respect to science productivity. The SPI includes a collection of items for tracking the production of science outputs and data practices, which are described and illustrated with examples. Several opportunities for further development of the initial inventory are highlighted, as well as potential for using the inventory as a tool to guide project management, funding, and research on citizen science.}, } @article {pmid29867252, year = {2018}, author = {Sanderson, EW and Walston, J and Robinson, JG}, title = {From Bottleneck to Breakthrough: Urbanization and the Future of Biodiversity Conservation.}, journal = {Bioscience}, volume = {68}, number = {6}, pages = {412-426}, pmid = {29867252}, issn = {0006-3568}, abstract = {For the first time in the Anthropocene, the global demographic and economic trends that have resulted in unprecedented destruction of the environment are now creating the necessary conditions for a possible renaissance of nature. Drawing reasonable inferences from current patterns, we can predict that 100 years from now, the Earth could be inhabited by between 6 and 8 billion people, with very few remaining in extreme poverty, most living in towns and cities, and nearly all participating in a technologically driven, interconnected market economy. Building on the scholarship of others in demography, economics, sociology, and conservation biology, here, we articulate a theory of social-environmental change that describes the simultaneous and interacting effects of urban lifestyles on fertility, poverty alleviation, and ideation. By recognizing the shifting dynamics of these macrodrivers, conservation practice has the potential to transform itself from a discipline managing declines ("bottleneck") to a transformative movement of recovery ("breakthrough").}, } @article {pmid29867223, year = {2018}, author = {Singh, I and Contreras, A and Cordero, J and Rubio, K and Dobersch, S and Günther, S and Jeratsch, S and Mehta, A and Krüger, M and Graumann, J and Seeger, W and Dobreva, G and Braun, T and Barreto, G}, title = {MiCEE is a ncRNA-protein complex that mediates epigenetic silencing and nucleolar organization.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {990-1001}, doi = {10.1038/s41588-018-0139-3}, pmid = {29867223}, issn = {1546-1718}, abstract = {The majority of the eukaryotic genome is transcribed into noncoding RNAs (ncRNAs), which are important regulators of different nuclear processes by controlling chromatin structure. However, the full extent of ncRNA function has remained elusive. Here we deciphered the function of the microRNA Mirlet7d as a key regulator of bidirectionally transcribed genes. We found that nuclear Mirlet7d binds ncRNAs expressed from these genes. Mirlet7d-ncRNA duplexes are further bound by C1D, which in turn targets the RNA exosome complex and the polycomb repressive complex 2 (PRC2) to the bidirectionally active loci. The exosome degrades the ncRNAs, whereas PRC2 induces heterochromatin and transcriptional silencing through EZH2. Moreover, this multicomponent RNA-protein complex, which we named MiCEE, tethers the regulated genes to the perinucleolar region and thus is required for proper nucleolar organization. Our study demonstrates that the MiCEE complex mediates epigenetic silencing of bidirectionally expressed genes and global genome organization.}, } @article {pmid29867222, year = {2018}, author = {Jacobs, J and Atkins, M and Davie, K and Imrichova, H and Romanelli, L and Christiaens, V and Hulselmans, G and Potier, D and Wouters, J and Taskiran, II and Paciello, G and González-Blas, CB and Koldere, D and Aibar, S and Halder, G and Aerts, S}, title = {The transcription factor Grainy head primes epithelial enhancers for spatiotemporal activation by displacing nucleosomes.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {1011-1020}, pmid = {29867222}, issn = {1546-1718}, support = {724226//European Research Council/International ; P40 OD018537/OD/NIH HHS/United States ; }, abstract = {Transcriptional enhancers function as docking platforms for combinations of transcription factors (TFs) to control gene expression. How enhancer sequences determine nucleosome occupancy, TF recruitment and transcriptional activation in vivo remains unclear. Using ATAC-seq across a panel of Drosophila inbred strains, we found that SNPs affecting binding sites of the TF Grainy head (Grh) causally determine the accessibility of epithelial enhancers. We show that deletion and ectopic expression of Grh cause loss and gain of DNA accessibility, respectively. However, although Grh binding is necessary for enhancer accessibility, it is insufficient to activate enhancers. Finally, we show that human Grh homologs-GRHL1, GRHL2 and GRHL3-function similarly. We conclude that Grh binding is necessary and sufficient for the opening of epithelial enhancers but not for their activation. Our data support a model positing that complex spatiotemporal expression patterns are controlled by regulatory hierarchies in which pioneer factors, such as Grh, establish tissue-specific accessible chromatin landscapes upon which other factors can act.}, } @article {pmid29867221, year = {2018}, author = {Karlsson, J and Valind, A and Holmquist Mengelbier, L and Bredin, S and Cornmark, L and Jansson, C and Wali, A and Staaf, J and Viklund, B and Øra, I and Börjesson, A and Backman, T and Braekeveldt, N and Sandstedt, B and Pal, N and Isaksson, A and Lackner, BG and Jonson, T and Bexell, D and Gisselsson, D}, title = {Four evolutionary trajectories underlie genetic intratumoral variation in childhood cancer.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {944-950}, doi = {10.1038/s41588-018-0131-y}, pmid = {29867221}, issn = {1546-1718}, abstract = {A major challenge to personalized oncology is that driver mutations vary among cancer cells inhabiting the same tumor. Whether this reflects principally disparate patterns of Darwinian evolution in different tumor regions has remained unexplored1-5. We mapped the prevalence of genetically distinct clones over 250 regions in 54 childhood cancers. This showed that primary tumors can simultaneously follow up to four evolutionary trajectories over different anatomic areas. The most common pattern consists of subclones with very few mutations confined to a single tumor region. The second most common is a stable coexistence, over vast areas, of clones characterized by changes in chromosome numbers. This is contrasted by a third, less frequent, pattern where a clone with driver mutations or structural chromosome rearrangements emerges through a clonal sweep to dominate an anatomical region. The fourth and rarest pattern is the local emergence of a myriad of clones with TP53 inactivation. Death from disease was limited to tumors exhibiting the two last, most dynamic patterns.}, } @article {pmid29867162, year = {2018}, author = {Zhang, ZY and Romano, D and Ivison, RJ and Papadopoulos, PP and Matteucci, F}, title = {Stellar populations dominated by massive stars in dusty starburst galaxies across cosmic time.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {260-263}, doi = {10.1038/s41586-018-0196-x}, pmid = {29867162}, issn = {1476-4687}, abstract = {All measurements of cosmic star formation must assume an initial distribution of stellar masses-the stellar initial mass function-in order to extrapolate from the star-formation rate measured for typically rare, massive stars (of more than eight solar masses) to the total star-formation rate across the full stellar mass spectrum 1 . The shape of the stellar initial mass function in various galaxy populations underpins our understanding of the formation and evolution of galaxies across cosmic time 2 . Classical determinations of the stellar initial mass function in local galaxies are traditionally made at ultraviolet, optical and near-infrared wavelengths, which cannot be probed in dust-obscured galaxies2,3, especially distant starbursts, whose apparent star-formation rates are hundreds to thousands of times higher than in the Milky Way, selected at submillimetre (rest-frame far-infrared) wavelengths4,5. The 13C/18O isotope abundance ratio in the cold molecular gas-which can be probed via the rotational transitions of the 13CO and C18O isotopologues-is a very sensitive index of the stellar initial mass function, with its determination immune to the pernicious effects of dust. Here we report observations of 13CO and C18O emission for a sample of four dust-enshrouded starbursts at redshifts of approximately two to three, and find unambiguous evidence for a top-heavy stellar initial mass function in all of them. A low 13CO/C18O ratio for all our targets-alongside a well tested, detailed chemical evolution model benchmarked on the Milky Way 6 -implies that there are considerably more massive stars in starburst events than in ordinary star-forming spiral galaxies. This can bring these extraordinary starbursts closer to the 'main sequence' of star-forming galaxies 7 , although such main-sequence galaxies may not be immune to changes in initial stellar mass function, depending on their star-formation densities.}, } @article {pmid29867161, year = {2018}, author = {Hicks, J and Vasko, P and Goicoechea, JM and Aldridge, S}, title = {Publisher Correction: Synthesis, structure and reaction chemistry of a nucleophilic aluminyl anion.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {E24}, doi = {10.1038/s41586-018-0168-1}, pmid = {29867161}, issn = {1476-4687}, abstract = {In Fig. 1 of this Letter, the hydrogen (H) atoms attached to each of the two nitrogen (N) atoms in the chemical structure of (NON)H2 were inadvertently missing. The original figure has been corrected online.}, } @article {pmid29867160, year = {2018}, author = {Banerjee, M and Heiblum, M and Umansky, V and Feldman, DE and Oreg, Y and Stern, A}, title = {Observation of half-integer thermal Hall conductance.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {205-210}, doi = {10.1038/s41586-018-0184-1}, pmid = {29867160}, issn = {1476-4687}, abstract = {Topological states of matter are characterized by topological invariants, which are physical quantities whose values are quantized and do not depend on the details of the system (such as its shape, size and impurities). Of these quantities, the easiest to probe is the electrical Hall conductance, and fractional values (in units of e2/h, where e is the electronic charge and h is the Planck constant) of this quantity attest to topologically ordered states, which carry quasiparticles with fractional charge and anyonic statistics. Another topological invariant is the thermal Hall conductance, which is harder to measure. For the quantized thermal Hall conductance, a fractional value in units of κ0 (κ0 = π2kB2/(3h), where kB is the Boltzmann constant) proves that the state of matter is non-Abelian. Such non-Abelian states lead to ground-state degeneracy and perform topological unitary transformations when braided, which can be useful for topological quantum computation. Here we report measurements of the thermal Hall conductance of several quantum Hall states in the first excited Landau level and find that the thermal Hall conductance of the 5/2 state is compatible with a half-integer value of 2.5κ0, demonstrating its non-Abelian nature.}, } @article {pmid29867101, year = {2018}, author = {Hendy, J and Welker, F and Demarchi, B and Speller, C and Warinner, C and Collins, MJ}, title = {Author Correction: A guide to ancient protein studies.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1190}, doi = {10.1038/s41559-018-0590-7}, pmid = {29867101}, issn = {2397-334X}, abstract = {In the version of this Perspective originally published, in the third paragraph of the section 'Selection and sampling', the sentence beginning 'Pyrolysis-gas chromatography' should have also referred to high-performance liquid chromatography; the sentence has now been amended to read 'Pyrolysis-gas chromatography/mass spectrometry (py-GC/MS) and high-performance liquid chromatography (HPLC) can be used to detect the presence of amino acids62 in any putative proteinaceous sample.'}, } @article {pmid29867100, year = {2018}, author = {Cameron, EK and Martins, IS and Lavelle, P and Mathieu, J and Tedersoo, L and Gottschall, F and Guerra, CA and Hines, J and Patoine, G and Siebert, J and Winter, M and Cesarz, S and Delgado-Baquerizo, M and Ferlian, O and Fierer, N and Kreft, H and Lovejoy, TE and Montanarella, L and Orgiazzi, A and Pereira, HM and Phillips, HRP and Settele, J and Wall, DH and Eisenhauer, N}, title = {Global gaps in soil biodiversity data.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1042-1043}, pmid = {29867100}, issn = {2397-334X}, } @article {pmid29867099, year = {2018}, author = {Bliege Bird, R and Nimmo, D}, title = {Restore the lost ecological functions of people.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1050-1052}, doi = {10.1038/s41559-018-0576-5}, pmid = {29867099}, issn = {2397-334X}, } @article {pmid29867096, year = {2018}, author = {Breitbart, M and Bonnain, C and Malki, K and Sawaya, NA}, title = {Phage puppet masters of the marine microbial realm.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {754-766}, doi = {10.1038/s41564-018-0166-y}, pmid = {29867096}, issn = {2058-5276}, abstract = {Viruses numerically dominate our oceans; however, we have only just begun to document the diversity, host range and infection dynamics of marine viruses, as well as the subsequent effects of infection on both host cell metabolism and oceanic biogeochemistry. Bacteriophages (that is, phages: viruses that infect bacteria) are highly abundant and are known to play critical roles in bacterial mortality, biogeochemical cycling and horizontal gene transfer. This Review Article summarizes current knowledge of marine viral ecology and highlights the importance of phage particles to the dissolved organic matter pool, as well as the complex interactions between phages and their bacterial hosts. We emphasize the newly recognized roles of phages as puppet masters of their bacterial hosts, where phages are capable of altering the metabolism of infected bacteria through the expression of auxiliary metabolic genes and the redirection of host gene expression patterns. Finally, we propose the 'royal family model' as a hypothesis to describe successional patterns of bacteria and phages over time in marine systems, where despite high richness and significant seasonal differences, only a small number of phages appear to continually dominate a given marine ecosystem. Although further testing is required, this model provides a framework for assessing the specificity and ecological consequences of phage-host dynamics.}, } @article {pmid29867093, year = {2018}, author = {Beaton, R}, title = {A fresh approach to stellar benchmarking.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {33-35}, doi = {10.1038/d41586-018-05306-7}, pmid = {29867093}, issn = {1476-4687}, } @article {pmid29866924, year = {2018}, author = {Sarabian, C and Belais, R and MacIntosh, AJJ}, title = {Feeding decisions under contamination risk in bonobos.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866924}, issn = {1471-2970}, abstract = {Threats from parasites and pathogens are ubiquitous, and many use pathways that exploit host trophic interactions for their transmission. As such, host organisms have evolved a behavioural immune system to facilitate contamination-risk assessment and avoidance of potential contaminants in various contexts, including feeding. Detecting pathogen threats can rely on different sensory modalities allowing animals to screen for a wide array of contaminants. Here, we present a series of experiments in which bonobos showed clear avoidance of contaminated food items, and were sensitive to risk along a contamination probability gradient. Across experiments, bonobos appeared to use multisensorial cues to inform their feeding decisions. In addition, bonobos showed reduced tactile, gustatory and tool use activities when in the presence of contaminant versus control odours in a challenging foraging context. Our experiments build on previous work conducted in Japanese macaques and chimpanzees aiming at a better understanding of the ways in which the behavioural immune system operates in primates.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866923, year = {2018}, author = {Sarabian, C and Curtis, V and McMullan, R}, title = {Evolution of pathogen and parasite avoidance behaviours.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866923}, issn = {1471-2970}, abstract = {All free-living animals are subject to intense selection pressure from parasites and pathogens resulting in behavioural adaptations that can help potential hosts to avoid falling prey to parasites. This special issue on the evolution of parasite avoidance behaviour was compiled following a Royal Society meeting in 2017. Here we have assembled contributions from a wide range of disciplines including genetics, ecology, parasitology, behavioural science, ecology, psychology and epidemiology on the disease avoidance behaviour of a wide range of species. Taking an interdisciplinary and cross-species perspective allows us to sketch out the strategies, mechanisms and consequences of parasite avoidance and to identify gaps and further questions. Parasite avoidance strategies must include avoiding parasites themselves and cues to their presence in conspecifics, heterospecifics, foods and habitat. Further, parasite avoidance behaviour can be directed at constructing parasite-retardant niches. Mechanisms of parasite avoidance behaviour are generally less well characterized, though nematodes, rodents and human studies are beginning to elucidate the genetic, hormonal and neural architecture that allows animals to recognize and respond to cues of parasite threat. While the consequences of infection are well characterized in humans, we still have much to learn about the epidemiology of parasites of other species, as well as the trade-offs that hosts make in parasite defence versus other beneficial investments like mating and foraging. Finally, in this overview we conclude that it is legitimate to use the word 'disgust' to describe parasite avoidance systems, in the same way that 'fear' is used to describe animal predator avoidance systems. Understanding disgust across species offers an excellent system for investigating the strategies, mechanisms and consequences of behaviour and could be a vital contribution towards the understanding and conservation of our planet's ecosystems.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866922, year = {2018}, author = {Anderson, A and McMullan, R}, title = {Neuronal and non-neuronal signals regulate Caernorhabditis elegans avoidance of contaminated food.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866922}, issn = {1471-2970}, support = {P40 OD010440/OD/NIH HHS/United States ; }, abstract = {One way in which animals minimize the risk of infection is to reduce their contact with contaminated food. Here, we establish a model of pathogen-contaminated food avoidance using the nematode worm Caernorhabditis elegans We find that avoidance of pathogen-contaminated food protects C. elegans from the deleterious effects of infection and, using genetic approaches, demonstrate that multiple sensory neurons are required for this avoidance behaviour. In addition, our results reveal that the avoidance of contaminated food requires bacterial adherence to non-neuronal cells in the tail of C. elegans that are also required for the cellular immune response. Previous studies in C. elegans have contributed significantly to our understanding of molecular and cellular basis of host-pathogen interactions and our model provides a unique opportunity to gain basic insights into how animals avoid contaminated food.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866921, year = {2018}, author = {Curtis, V and de Barra, M}, title = {The structure and function of pathogen disgust.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866921}, issn = {1471-2970}, abstract = {Researchers have long noted that many of the multiple elicitors of disgust have some relation to infectious disease. There is an emerging consensus that disgust evolved in Animalia to direct the behaviours that reduce risk of infection, so-called 'parasite avoidance theory'. If this is correct, then the disgust motive should be structured in a manner that reflects the ways in which infectious disease can be avoided. In this study, we generated a set of items based on the epidemiology of disease transmission. These were then rated for their capacity to elicit disgust by a large, predominantly North American/UK sample and subjected to factor analysis to identify latent variables. While a number of plausible factor solutions emerged, Velicer's MAP (minimum average partial) test suggested six domains: atypical appearance, lesions, sex, hygiene, food and animals. This structure did not exactly mirror the transmission routes of infections, as we initially predicted, but it may rather reflect distinct kinds of behavioural tasks involved in avoiding disease. This finding makes sense from the perspective of a cognitive system that evolved under selection for a behavioural response to threats from the social and biological environment. We suggest that regularly occurring types of infectious disease problems have produced regularities in the domain structure of pathogen disgust and discuss the implications of these results for understanding the structure, function and measurement of motives such as disgust in humans and other animals.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866920, year = {2018}, author = {Kupfer, TR and Fessler, DMT}, title = {Ectoparasite defence in humans: relationships to pathogen avoidance and clinical implications.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866920}, issn = {1471-2970}, abstract = {Currently, disgust is regarded as the main adaptation for defence against pathogens and parasites in humans. Disgust's motivational and behavioural features, including withdrawal, nausea, appetite suppression and the urge to vomit, defend effectively against ingesting or touching sources of pathogens. However, ectoparasites do not attack their hosts via ingestion, but rather actively attach themselves to the body surface. Accordingly, by itself, disgust offers limited defence against ectoparasites. We propose that, like non-human animals, humans have a distinct ectoparasite defence system that includes cutaneous sensory mechanisms, itch-generation mechanisms and grooming behaviours. The existence of adaptations for ectoparasite defence is supported by abundant evidence from non-human animals, as well as more recent evidence concerning human responses to ectoparasite cues. Several clinical disorders may be dysfunctions of the ectoparasite defence system, including some that are pathologies of grooming, such as skin picking and trichotillomania, and others, such as delusory parasitosis and trypophobia, which are pathologies of ectoparasite detection. We conclude that future research should explore both distinctions between, and overlap across, ectoparasite defence systems and pathogen avoidance systems, as doing so will not only illuminate proximate motivational systems, including disgust, but may also reveal important clinical and social consequences.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866919, year = {2018}, author = {Kavaliers, M and Choleris, E}, title = {The role of social cognition in parasite and pathogen avoidance.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866919}, issn = {1471-2970}, abstract = {The acquisition and use of social information are integral to social behaviour and parasite/pathogen avoidance. This involves social cognition which encompasses mechanisms for acquiring, processing, retaining and acting on social information. Social cognition entails the acquisition of social information about others (i.e. social recognition) and from others (i.e. social learning). Social cognition involves assessing other individuals and their infection status and the pathogen and parasite threat they pose and deciding about when and how to interact with them. Social cognition provides a framework for examining pathogen and parasite avoidance behaviours and their associated neurobiological mechanisms. Here, we briefly consider the relationships between social cognition and olfactory-mediated pathogen and parasite avoidance behaviours. We briefly discuss aspects of (i) social recognition of actual and potentially infected individuals and the impact of parasite/pathogen threat on mate and social partner choice; (ii) the roles of 'out-groups' (strangers, unfamiliar individuals) and 'in-groups' (familiar individuals) in the expression of parasite/pathogen avoidance behaviours; (iii) individual and social learning, i.e. the utilization of the pathogen recognition and avoidance responses of others; and (iv) the neurobiological mechanisms, in particular the roles of the nonapeptide, oxytocin and steroid hormones (oestrogens) associated with social cognition and parasite/pathogen avoidance.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866918, year = {2018}, author = {Hart, BL and Hart, LA}, title = {How mammals stay healthy in nature: the evolution of behaviours to avoid parasites and pathogens.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866918}, issn = {1471-2970}, abstract = {Mammals live and thrive in environments presenting ongoing threats from parasites in the form of biting flies, ticks and intestinal worms and from pathogens as wound contaminants and agents of infectious disease. Several strategies have evolved that enable animals to deal with parasites and pathogens, including eliminating away from the sleeping-resting areas, use of an array of grooming techniques, use of saliva in licking, and consuming medicinal plant-based compounds. These strategies all are species-specific and reflect the particular environment that the animal inhabits.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866917, year = {2018}, author = {Tybur, JM and Çınar, Ç and Karinen, AK and Perone, P}, title = {Why do people vary in disgust?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866917}, issn = {1471-2970}, abstract = {People vary in the degree to which they experience disgust toward-and, consequently, avoid-cues to pathogens. Prodigious work has measured this variation and observed that it relates to, among other things, personality, psychopathological tendencies, and moral and political sentiments. Less work has sought to generate hypotheses aimed at explaining why this variation exists in the first place, and even less work has evaluated how well data support these hypotheses. In this paper, we present and review the evidence supporting three such proposals. First, researchers have suggested that variability reflects a general tendency to experience anxiety or emotional distress. Second, researchers have suggested that variability arises from parental modelling, with offspring calibrating their pathogen avoidance based on their parents' reactions to pathogen cues. Third, researchers have suggested that individuals calibrate their disgust sensitivity to the parasite stress of the ecology in which they develop. We conclude that none of these hypotheses is supported by existing data, and we propose directions for future research aimed at better understanding this variation.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866916, year = {2018}, author = {Lieberman, D and Billingsley, J and Patrick, C}, title = {Consumption, contact and copulation: how pathogens have shaped human psychological adaptations.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866916}, issn = {1471-2970}, abstract = {Disgust is an emotion intimately linked to pathogen avoidance. Building on prior work, we suggest disgust is an output of programmes that evolved to address three separate adaptive problems: what to eat, what to touch and with whom to have sex. We briefly discuss the architecture of these programmes, specifying their perceptual inputs and the contextual factors that enable them to generate adaptive and flexible behaviour. We propose that our sense of disgust is the result of these programmes and occurs when information-processing circuitries assess low expected values of consumption, low expected values of contact or low expected sexual values. This conception of disgust differs from prior models in that it dissects pathogen-related selection pressures into adaptive problems related to consumption and contact rather than assuming just one pathogen disgust system, and it excludes moral disgust from the domain of disgust proper. Instead, we illustrate how low expected values of consumption and contact as well as low expected sexual values can be used by our moral psychology to provide multiple causal links between disgust and morality.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866915, year = {2018}, author = {Behringer, DC and Karvonen, A and Bojko, J}, title = {Parasite avoidance behaviours in aquatic environments.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866915}, issn = {1471-2970}, abstract = {Parasites, including macroparasites, protists, fungi, bacteria and viruses, can impose a heavy burden upon host animals. However, hosts are not without defences. One aspect of host defence, behavioural avoidance, has been studied in the terrestrial realm for over 50 years, but was first reported from the aquatic environment approximately 20 years ago. Evidence has mounted on the importance of parasite avoidance behaviours and it is increasingly apparent that there are core similarities in the function and benefit of this defence mechanism between terrestrial and aquatic systems. However, there are also stark differences driven by the unique biotic and abiotic characteristics of terrestrial and aquatic (marine and freshwater) environments. Here, we review avoidance behaviours in a comparative framework and highlight the characteristics of each environment that drive differences in the suite of mechanisms and cues that animals use to avoid parasites. We then explore trade-offs, potential negative effects of avoidance behaviour and the influence of human activities on avoidance behaviours. We conclude that avoidance behaviours are understudied in aquatic environments but can have significant implications for disease ecology and epidemiology, especially considering the accelerating emergence and re-emergence of parasites.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866914, year = {2018}, author = {Al Toufailia, H and Evison, SEF and Hughes, WOH and Ratnieks, FLW}, title = {Both hygienic and non-hygienic honeybee, Apis mellifera, colonies remove dead and diseased larvae from open brood cells.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866914}, issn = {1471-2970}, abstract = {Hygienic behaviour is a group defence in which dead or diseased individuals are excluded. In the honeybee, Apis mellifera, hygienic behaviour refers to uncapping and removing dead and diseased larvae and pupae from sealed brood cells. We quantified removal of freeze-killed and chalkbrood-infected larvae from open cells in 20 colonies. We also measured removal of freeze-killed brood from sealed cells. Study colonies ranged from non-hygienic to fully hygienic (52-100% removal within 2 days). All larvae killed in open cells were removed. This shows that all colonies, including those with low hygienic behaviour against dead brood in sealed cells, are highly hygienic against dead brood in open cells and suggests that low hygienic behaviour against dead brood in sealed cells is a trait in its own right. This may also contribute to understanding why hygienic behaviour is uncommon in A. mellifera, which is puzzling as it reduces several diseases without detrimental effects. In particular, the result provides indirect support for the hypothesis that there are two adaptive peaks conferring disease resistance: (i) high hygienic behaviour: diseased brood are removed quickly, in some cases before becoming infective; (ii) low hygienic behaviour: diseased brood remain isolated within sealed cells.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866913, year = {2018}, author = {Grüter, C and Jongepier, E and Foitzik, S}, title = {Insect societies fight back: the evolution of defensive traits against social parasites.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866913}, issn = {1471-2970}, abstract = {Insect societies face many social parasites that exploit their altruistic behaviours or their resources. Due to the fitness costs these social parasites incur, hosts have evolved various behavioural, chemical, architectural and morphological defence traits. Similar to bacteria infecting multicellular hosts, social parasites have to successfully go through several steps to exploit their hosts. Here, we review how social insects try to interrupt this sequence of events. They can avoid parasite contact by choosing to nest in parasite-free locales or evade attacks by adapting their colony structure. Once social parasites attack, hosts attempt to detect them, which can be facilitated by adjustments in colony odour. If social parasites enter the nest, hosts can either aggressively defend their colony or take their young and flee. Nest structures are often shaped to prevent social parasite invasion or to safeguard host resources. Finally, if social parasites successfully establish themselves in host nests, hosts can rebel by killing the parasite brood or by reproducing in the parasites' presence. Hosts of social parasites can therefore develop multiple traits, leading to the evolution of complex defence portfolios of co-dependent traits. Social parasites can respond to these multi-level defences with counter-adaptations, potentially leading to geographical mosaics of coevolution.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866912, year = {2018}, author = {Coulson, G and Cripps, JK and Garnick, S and Bristow, V and Beveridge, I}, title = {Parasite insight: assessing fitness costs, infection risks and foraging benefits relating to gastrointestinal nematodes in wild mammalian herbivores.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866912}, issn = {1471-2970}, abstract = {Mammalian herbivores are typically infected by parasitic nematodes, which are acquired through direct, faecal-oral transmission. These parasites can cause significant production losses in domestic livestock, but much less is known about impacts on wild mammalian hosts. We review three elements of parasitism from the host's perspective: fitness costs of infection, risks of infection during foraging and benefits of nutritious pasture. The majority of wildlife studies have been observational, but experimental manipulation is increasing. Treatment with anthelmintics to manipulate parasite load has revealed varied impacts of parasites on fitness variables across host species, but has not produced consistent evidence for parasite-induced anorexia or impaired body condition. Some experimental studies of infection risk have manipulated faecal contamination and detected faecal avoidance by hosts. Only two field studies have explored the trade-off between infection risk and nutritional benefit generated by avoidance of contaminated patches. Overall, field studies of costs, risks and benefits of the host-parasite relationship are limited and few have examined more than one of these elements. Parasitism has much in common with predation, and future insights into anti-parasite responses by wild hosts could be gained from the conceptual and technical developments in research on anti-predator behaviour.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866911, year = {2018}, author = {Bush, SE and Clayton, DH}, title = {Anti-parasite behaviour of birds.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1751}, pages = {}, pmid = {29866911}, issn = {1471-2970}, abstract = {Birds have many kinds of internal and external parasites, including viruses, bacteria and fungi, as well as protozoa, helminths and arthropods. Because parasites have negative effects on host fitness, selection favours the evolution of anti-parasite defences, many of which involve behaviour. We provide a brief review of anti-parasite behaviours in birds, divided into five major categories: (i) body maintenance, (ii) nest maintenance, (iii) avoidance of parasitized prey, (iv) migration and (v) tolerance. We evaluate the adaptive significance of the different behaviours and note cases in which additional research is particularly needed. We briefly consider the interaction of different behaviours, such as sunning and preening, and how behavioural defences may interact with other forms of defence, such as immune responses. We conclude by suggesting some general questions that need to be addressed concerning the nature of anti-parasite behaviour in birds.This article is part of the Theo Murphy meeting issue 'Evolution of pathogen and parasite avoidance behaviours'.}, } @article {pmid29866856, year = {2018}, author = {Kozyrev, V and Staadt, R and Eysel, UT and Jancke, D}, title = {TMS-induced neuronal plasticity enables targeted remodeling of visual cortical maps.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6476-6481}, pmid = {29866856}, issn = {1091-6490}, mesh = {Animals ; Brain Mapping/methods ; Cats ; Neuronal Plasticity/*physiology ; Neurons/*physiology ; Orientation/physiology ; Photic Stimulation/methods ; Transcranial Magnetic Stimulation/methods ; Visual Cortex/*physiology ; }, abstract = {Transcranial magnetic stimulation (TMS) has become a popular clinical method to modify cortical processing. The events underlying TMS-induced functional changes remain, however, largely unknown because current noninvasive recording methods lack spatiotemporal resolution or are incompatible with the strong TMS-associated electrical field. In particular, an answer to the question of how the relatively unspecific nature of TMS stimulation leads to specific neuronal reorganization, as well as a detailed picture of TMS-triggered reorganization of functional brain modules, is missing. Here we used real-time optical imaging in an animal experimental setting to track, at submillimeter range, TMS-induced functional changes in visual feature maps over several square millimeters of the brain's surface. We show that high-frequency TMS creates a transient cortical state with increased excitability and increased response variability, which opens a time window for enhanced plasticity. Visual stimulation (i.e., 30 min of passive exposure) with a single orientation applied during this TMS-induced permissive period led to enlarged imprinting of the chosen orientation on the visual map across visual cortex. This reorganization was stable for hours and was characterized by a systematic shift in orientation preference toward the trained orientation. Thus, TMS can noninvasively trigger a targeted large-scale remodeling of fundamentally mature functional architecture in early sensory cortex.}, } @article {pmid29866855, year = {2018}, author = {Arandkar, S and Furth, N and Elisha, Y and Nataraj, NB and van der Kuip, H and Yarden, Y and Aulitzky, W and Ulitsky, I and Geiger, B and Oren, M}, title = {Altered p53 functionality in cancer-associated fibroblasts contributes to their cancer-supporting features.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6410-6415}, pmid = {29866855}, issn = {1091-6490}, mesh = {Animals ; Cancer-Associated Fibroblasts/*metabolism/pathology ; Cell Line ; Cell Line, Tumor ; Cell Movement/physiology ; Cell Proliferation/physiology ; Coculture Techniques/methods ; Disease Progression ; Female ; HEK293 Cells ; Humans ; Mice ; Middle Aged ; Neoplasms/*metabolism/pathology ; Transcription, Genetic/physiology ; Transcriptome/physiology ; Tumor Microenvironment/physiology ; Tumor Suppressor Protein p53/*metabolism ; }, abstract = {Within the tumor microenvironment, cancer cells coexist with noncancerous adjacent cells that constitute the tumor microenvironment and impact tumor growth through diverse mechanisms. In particular, cancer-associated fibroblasts (CAFs) promote tumor progression in multiple ways. Earlier studies have revealed that in normal fibroblasts (NFs), p53 plays a cell nonautonomous tumor-suppressive role to restrict tumor growth. We now wished to investigate the role of p53 in CAFs. Remarkably, we found that the transcriptional program supported by p53 is altered substantially in CAFs relative to NFs. In agreement, the p53-dependent secretome is also altered in CAFs. This transcriptional rewiring renders p53 a significant contributor to the distinct intrinsic features of CAFs, as well as promotes tumor cell migration and invasion in culture. Concordantly, the ability of CAFs to promote tumor growth in mice is greatly compromised by depletion of their endogenous p53. Furthermore, cocultivation of NFs with cancer cells renders their p53-dependent transcriptome partially more similar to that of CAFs. Our findings raise the intriguing possibility that tumor progression may entail a nonmutational conversion ("education") of stromal p53, from tumor suppressive to tumor supportive.}, } @article {pmid29866854, year = {2018}, author = {Meier, M and Hulva, J and Jakub, Z and Pavelec, J and Setvin, M and Bliem, R and Schmid, M and Diebold, U and Franchini, C and Parkinson, GS}, title = {Water agglomerates on Fe3O4(001).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5642-E5650}, pmid = {29866854}, issn = {1091-6490}, abstract = {Determining the structure of water adsorbed on solid surfaces is a notoriously difficult task and pushes the limits of experimental and theoretical techniques. Here, we follow the evolution of water agglomerates on Fe3O4(001); a complex mineral surface relevant in both modern technology and the natural environment. Strong OH-H2O bonds drive the formation of partially dissociated water dimers at low coverage, but a surface reconstruction restricts the density of such species to one per unit cell. The dimers act as an anchor for further water molecules as the coverage increases, leading first to partially dissociated water trimers, and then to a ring-like, hydrogen-bonded network that covers the entire surface. Unraveling this complexity requires the concerted application of several state-of-the-art methods. Quantitative temperature-programmed desorption (TPD) reveals the coverage of stable structures, monochromatic X-ray photoelectron spectroscopy (XPS) shows the extent of partial dissociation, and noncontact atomic force microscopy (AFM) using a CO-functionalized tip provides a direct view of the agglomerate structure. Together, these data provide a stringent test of the minimum-energy configurations determined via a van der Waals density functional theory (DFT)-based genetic search.}, } @article {pmid29866853, year = {2018}, author = {Cai, C and Fordsmann, JC and Jensen, SH and Gesslein, B and Lønstrup, M and Hald, BO and Zambach, SA and Brodin, B and Lauritzen, MJ}, title = {Stimulation-induced increases in cerebral blood flow and local capillary vasoconstriction depend on conducted vascular responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5796-E5804}, pmid = {29866853}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/metabolism ; Animals ; Arterioles/metabolism/physiology ; Capillaries/metabolism/*physiology ; Cerebrovascular Circulation/*physiology ; Female ; Functional Neuroimaging/methods ; Male ; Mice ; Pericytes/metabolism/physiology ; Receptors, Purinergic P2/metabolism ; Somatosensory Cortex/*blood supply/metabolism/physiology ; Vasoconstriction/*physiology ; Vasodilation/physiology ; }, abstract = {Functional neuroimaging, such as fMRI, is based on coupling neuronal activity and accompanying changes in cerebral blood flow (CBF) and metabolism. However, the relationship between CBF and events at the level of the penetrating arterioles and capillaries is not well established. Recent findings suggest an active role of capillaries in CBF control, and pericytes on capillaries may be major regulators of CBF and initiators of functional imaging signals. Here, using two-photon microscopy of brains in living mice, we demonstrate that stimulation-evoked increases in synaptic activity in the mouse somatosensory cortex evokes capillary dilation starting mostly at the first- or second-order capillary, propagating upstream and downstream at 5-20 µm/s. Therefore, our data support an active role of pericytes in cerebrovascular control. The gliotransmitter ATP applied to first- and second-order capillaries by micropipette puffing induced dilation, followed by constriction, which also propagated at 5-20 µm/s. ATP-induced capillary constriction was blocked by purinergic P2 receptors. Thus, conducted vascular responses in capillaries may be a previously unidentified modulator of cerebrovascular function and functional neuroimaging signals.}, } @article {pmid29866852, year = {2018}, author = {Steckelberg, AL and Akiyama, BM and Costantino, DA and Sit, TL and Nix, JC and Kieft, JS}, title = {A folded viral noncoding RNA blocks host cell exoribonucleases through a conformationally dynamic RNA structure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6404-6409}, pmid = {29866852}, issn = {1091-6490}, support = {F32 GM117730/GM/NIGMS NIH HHS/United States ; P30 CA046934/CA/NCI NIH HHS/United States ; R35 GM118070/GM/NIGMS NIH HHS/United States ; R01 AI133348/AI/NIAID NIH HHS/United States ; S10 OD012033/OD/NIH HHS/United States ; }, mesh = {3' Untranslated Regions/genetics ; Animals ; Base Sequence ; Exoribonucleases/*metabolism ; Flavivirus/*genetics ; Host-Pathogen Interactions/*genetics ; Nucleic Acid Conformation ; RNA Folding/*genetics ; RNA Stability/genetics ; RNA, Viral/*genetics ; }, abstract = {Folded RNA elements that block processive 5' → 3' cellular exoribonucleases (xrRNAs) to produce biologically active viral noncoding RNAs have been discovered in flaviviruses, potentially revealing a new mode of RNA maturation. However, whether this RNA structure-dependent mechanism exists elsewhere and, if so, whether a singular RNA fold is required, have been unclear. Here we demonstrate the existence of authentic RNA structure-dependent xrRNAs in dianthoviruses, plant-infecting viruses unrelated to animal-infecting flaviviruses. These xrRNAs have no sequence similarity to known xrRNAs; thus, we used a combination of biochemistry and virology to characterize their sequence requirements and mechanism of stopping exoribonucleases. By solving the structure of a dianthovirus xrRNA by X-ray crystallography, we reveal a complex fold that is very different from that of the flavivirus xrRNAs. However, both versions of xrRNAs contain a unique topological feature, a pseudoknot that creates a protective ring around the 5' end of the RNA structure; this may be a defining structural feature of xrRNAs. Single-molecule FRET experiments reveal that the dianthovirus xrRNAs undergo conformational changes and can use "codegradational remodeling," exploiting the exoribonucleases' degradation-linked helicase activity to help form their resistant structure; such a mechanism has not previously been reported. Convergent evolution has created RNA structure-dependent exoribonuclease resistance in different contexts, which establishes it as a general RNA maturation mechanism and defines xrRNAs as an authentic functional class of RNAs.}, } @article {pmid29866851, year = {2018}, author = {Rotskoff, GM and Geissler, PL}, title = {Robust nonequilibrium pathways to microcompartment assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6341-6346}, pmid = {29866851}, issn = {1091-6490}, mesh = {Bacterial Proteins/metabolism ; Carbon Dioxide/metabolism ; Cell Compartmentation/*physiology ; Computer Simulation ; Cyanobacteria/metabolism ; Models, Theoretical ; Molecular Dynamics Simulation ; Organelles/*metabolism ; Photosynthesis ; Ribulose-Bisphosphate Carboxylase/metabolism ; }, abstract = {Cyanobacteria sequester photosynthetic enzymes into microcompartments which facilitate the conversion of carbon dioxide into sugars. Geometric similarities between these structures and self-assembling viral capsids have inspired models that posit microcompartments as stable equilibrium arrangements of the constituent proteins. Here we describe a different mechanism for microcompartment assembly, one that is fundamentally nonequilibrium and yet highly reliable. This pathway is revealed by simulations of a molecular model resolving the size and shape of a cargo droplet and the extent and topography of an elastic shell. The resulting metastable microcompartment structures closely resemble those of carboxysomes, with a narrow size distribution and faceted shells. The essence of their assembly dynamics can be understood from a simpler mathematical model that combines elements of classical nucleation theory with continuum elasticity. These results highlight important control variables for achieving nanoscale encapsulation in general and for modulating the size and shape of carboxysomes in particular.}, } @article {pmid29866850, year = {2018}, author = {Henry, KF and Bui, AQ and Kawashima, T and Goldberg, RB}, title = {A shared cis-regulatory module activates transcription in the suspensor of plant embryos.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5824-E5833}, pmid = {29866850}, issn = {1091-6490}, mesh = {Gene Expression Regulation, Plant/genetics ; Gene Regulatory Networks/genetics ; Mixed Function Oxygenases/genetics ; Phaseolus/genetics ; Plant Proteins/genetics ; Plants, Genetically Modified/genetics ; RNA, Messenger/genetics ; Seeds/*genetics ; Tobacco/genetics ; Transcription, Genetic/*genetics ; }, abstract = {The mechanisms controlling the transcription of gene sets in specific regions of a plant embryo shortly after fertilization remain unknown. Previously, we showed that G564 mRNA, encoding a protein of unknown function, accumulates to high levels in the giant suspensor of both Scarlet Runner Bean (SRB) and Common Bean embryos, and a cis-regulatory module containing three unique DNA sequences, designated as the 10-bp, Region 2, and Fifth motifs, is required for G564 suspensor-specific transcription [Henry KF, et al. (2015) Plant Mol Biol 88:207-217; Kawashima T, et al. (2009) Proc Natl Acad Sci USA 106:3627-3632]. We tested the hypothesis that these motifs are also required for transcription of the SRB GA 20-oxidase gene, which encodes a gibberellic acid hormone biosynthesis enzyme and is coexpressed with G564 at a high level in giant bean suspensors. We used deletion and gain-of-function experiments in transgenic tobacco embryos to show that two GA 20-oxidase DNA regions are required for suspensor-specific transcription, one in the 5' UTR (+119 to +205) and another in the 5' upstream region (-341 to -316). Mutagenesis of sequences in these two regions determined that the cis-regulatory motifs required for G564 suspensor transcription are also required for GA 20-oxidase transcription within the suspensor, although the motif arrangement differs. Our results demonstrate the flexibility of motif positioning within a cis-regulatory module that activates gene transcription within giant bean suspensors and suggest that G564 and GA 20-oxidase comprise part of a suspensor gene regulatory network.}, } @article {pmid29866849, year = {2018}, author = {Mou, X and Souter, S and Du, J and Reeves, AZ and Lesser, CF}, title = {Synthetic bottom-up approach reveals the complex interplay of Shigella effectors in regulation of epithelial cell death.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6452-6457}, pmid = {29866849}, issn = {1091-6490}, support = {R01 AI064285/AI/NIAID NIH HHS/United States ; T32 AI007061/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/*metabolism ; Bacterial Secretion Systems/metabolism ; Cell Death/*physiology ; Cell Line, Tumor ; Epithelial Cells/*metabolism/microbiology ; Escherichia coli/metabolism ; HeLa Cells ; Host-Pathogen Interactions/physiology ; Humans ; Shigella/*metabolism ; Virulence Factors/metabolism ; }, abstract = {Over the course of an infection, many Gram-negative bacterial pathogens use complex nanomachines to directly inject tens to hundreds of proteins (effectors) into the cytosol of infected host cells. These effectors rewire processes to promote bacterial replication and spread. The roles of effectors in pathogenesis have traditionally been investigated by screening for phenotypes associated with their absence, a top-down approach that can be limited, as effectors often act in a functionally redundant or additive manner. Here we describe a synthetic Escherichia coli-based bottom-up platform to conduct gain-of-function screens for roles of individual Shigella effectors in pathogenesis. As proof of concept, we screened for Shigella effectors that limit cell death induced on cytosolic entry of bacteria into epithelial cells. Using this platform, in addition to OspC3, an effector known to inhibit cell death via pyroptosis, we have identified OspD2 and IpaH1.4 as cell death inhibitors. In contrast to almost all type III effectors, OspD2 does not target a host cell process, but rather regulates the activity of the Shigella type III secretion apparatus limiting the cytosolic delivery (translocation) of effectors during an infection. Remarkably, by limiting the translocation of a single effector, VirA, OspD2 controls the timing of epithelial cell death via calpain-mediated necrosis. Together, these studies provide insight into the intricate manner by which Shigella effectors interact to establish a productive intracytoplasmic replication niche before the death of infected epithelial cells.}, } @article {pmid29866848, year = {2018}, author = {Lipsitz, YY and Woodford, C and Yin, T and Hanna, JH and Zandstra, PW}, title = {Modulating cell state to enhance suspension expansion of human pluripotent stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6369-6374}, pmid = {29866848}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Bioreactors ; Cell Culture Techniques/methods ; Cell Differentiation/drug effects ; Cell Line ; Cytokines/pharmacology ; Germ Layers/cytology/drug effects ; Humans ; Pluripotent Stem Cells/*cytology/drug effects ; Small Molecule Libraries/pharmacology ; }, abstract = {The development of cell-based therapies to replace missing or damaged tissues within the body or generate cells with a unique biological activity requires a reliable and accessible source of cells. Human pluripotent stem cells (hPSC) have emerged as a strong candidate cell source capable of extended propagation in vitro and differentiation to clinically relevant cell types. However, the application of hPSC in cell-based therapies requires overcoming yield limitations in large-scale hPSC manufacturing. We explored methods to convert hPSC to alternative states of pluripotency with advantageous bioprocessing properties, identifying a suspension-based small-molecule and cytokine combination that supports increased single-cell survival efficiency, faster growth rates, higher densities, and greater expansion than control hPSC cultures. ERK inhibition was found to be essential for conversion to this altered state, but once converted, ERK inhibition led to a loss of pluripotent phenotype in suspension. The resulting suspension medium formulation enabled hPSC suspension yields 5.7 ± 0.2-fold greater than conventional hPSC in 6 d, for at least five passages. Treated cells remained pluripotent, karyotypically normal, and capable of differentiating into all germ layers. Treated cells could also be integrated into directed differentiated strategies as demonstrated by the generation of pancreatic progenitors (NKX6.1+/PDX1+ cells). Enhanced suspension-yield hPSC displayed higher oxidative metabolism and altered expression of adhesion-related genes. The enhanced bioprocess properties of this alternative pluripotent state provide a strategy to overcome cell manufacturing limitations of hPSC.}, } @article {pmid29866847, year = {2018}, author = {Barnett, JB and Michalis, C and Scott-Samuel, NE and Cuthill, IC}, title = {Distance-dependent defensive coloration in the poison frog Dendrobates tinctorius, Dendrobatidae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6416-6421}, pmid = {29866847}, issn = {1091-6490}, support = {BB/N007239/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Anura/*physiology ; Biological Mimicry/physiology ; Color ; Poisons/*toxicity ; Predatory Behavior/physiology ; }, abstract = {Poison dart frogs provide classic examples of warning signals: potent toxins signaled by distinctive, conspicuous coloration. We show that, counterintuitively, the bright yellow and blue-black color of Dendrobates tinctorius (Dendrobatidae) also provides camouflage. Through computational modeling of predator vision, and a screen-based detection experiment presenting frogs at different spatial resolutions, we demonstrate that at close range the frog is highly detectable, but from a distance the colors blend together, forming effective camouflage. This result was corroborated with an in situ experiment, which found survival to be background-dependent, a feature more associated with camouflage than aposematism. Our results suggest that in D. tinctorius the distribution of pattern elements, and the particular colors expressed, act as a highly salient close range aposematic signal, while simultaneously minimizing detectability to distant observers.}, } @article {pmid29866846, year = {2018}, author = {Chen, Z and Oh, D and Biswas, KH and Yu, CH and Zaidel-Bar, R and Groves, JT}, title = {Spatially modulated ephrinA1:EphA2 signaling increases local contractility and global focal adhesion dynamics to promote cell motility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5696-E5705}, pmid = {29866846}, issn = {1091-6490}, support = {U01 CA202241/CA/NCI NIH HHS/United States ; }, mesh = {Cell Adhesion/*physiology ; Cell Line, Tumor ; Cell Movement/*physiology ; Ephrin-A1/*metabolism ; Focal Adhesions/*metabolism/*physiology ; Humans ; Ligands ; Lipid Bilayers/metabolism ; Myosins/metabolism ; Paxillin/metabolism ; Phosphorylation/physiology ; Receptor, EphA2/*metabolism ; Signal Transduction/*physiology ; Up-Regulation/physiology ; src-Family Kinases/metabolism ; }, abstract = {Recent studies have revealed pronounced effects of the spatial distribution of EphA2 receptors on cellular response to receptor activation. However, little is known about molecular mechanisms underlying this spatial sensitivity, in part due to lack of experimental systems. Here, we introduce a hybrid live-cell patterned supported lipid bilayer experimental platform in which the sites of EphA2 activation and integrin adhesion are spatially controlled. Using a series of live-cell imaging and single-molecule tracking experiments, we map the transmission of signals from ephrinA1:EphA2 complexes. Results show that ligand-dependent EphA2 activation induces localized myosin-dependent contractions while simultaneously increasing focal adhesion dynamics throughout the cell. Mechanistically, Src kinase is activated at sites of ephrinA1:EphA2 clustering and subsequently diffuses on the membrane to focal adhesions, where it up-regulates FAK and paxillin tyrosine phosphorylation. EphrinA1:EphA2 signaling triggers multiple cellular responses with differing spatial dependencies to enable a directed migratory response to spatially resolved contact with ephrinA1 ligands.}, } @article {pmid29866845, year = {2018}, author = {Prabhakar, J and Johnson, EG and Nordahl, CW and Ghetti, S}, title = {Memory-related hippocampal activation in the sleeping toddler.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6500-6505}, pmid = {29866845}, issn = {1091-6490}, support = {R21 HD088928/HD/NICHD NIH HHS/United States ; }, mesh = {Brain Mapping/methods ; Child, Preschool ; Female ; Hippocampus/*physiology ; Humans ; Learning/physiology ; Magnetic Resonance Imaging/methods ; Male ; Memory/*physiology ; Mental Recall/*physiology ; Sleep/*physiology ; }, abstract = {Nonhuman research has implicated developmental processes within the hippocampus in the emergence and early development of episodic memory, but methodological challenges have hindered assessments of this possibility in humans. Here, we delivered a previously learned song and a novel song to 2-year-old toddlers during natural nocturnal sleep and, using functional magnetic resonance imaging, found that hippocampal activation was stronger for the learned song compared with the novel song. This was true regardless of whether the song was presented intact or backwards. Toddlers who remembered where and in the presence of which toy character they heard the song exhibited stronger hippocampal activation for the song. The results establish that hippocampal activation in toddlers reflects past experiences, persists despite some alteration of the stimulus, and is associated with behavior. This research sheds light on early hippocampal and memory functioning and offers an approach to interrogate the neural substrates of early memory.}, } @article {pmid29866844, year = {2018}, author = {Zhang, Y and Hwang, BJ and Liu, Z and Li, N and Lough, K and Williams, SE and Chen, J and Burette, SW and Diaz, LA and Su, MA and Xiao, S and Liu, Z}, title = {BP180 dysfunction triggers spontaneous skin inflammation in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6434-6439}, pmid = {29866844}, issn = {1091-6490}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; R01 AI040768/AI/NIAID NIH HHS/United States ; R01 AR070276/AR/NIAMS NIH HHS/United States ; R01 NS079683/NS/NINDS NIH HHS/United States ; }, mesh = {Adaptive Immunity/immunology ; Animals ; Autoantigens/immunology/*metabolism ; Cytokines/immunology/metabolism ; Histamine/immunology/metabolism ; Humans ; Immunoglobulin E/blood ; Inflammation/blood/immunology/*metabolism ; Keratinocytes/immunology/metabolism ; Mice ; Mice, Inbred C57BL ; Non-Fibrillar Collagens/immunology/*metabolism ; Pemphigoid, Bullous/immunology/metabolism ; Pruritus/blood/immunology/metabolism ; Skin/immunology/*metabolism ; }, abstract = {BP180, also known as collagen XVII, is a hemidesmosomal component and plays a key role in maintaining skin dermal/epidermal adhesion. Dysfunction of BP180, either through genetic mutations in junctional epidermolysis bullosa (JEB) or autoantibody insult in bullous pemphigoid (BP), leads to subepidermal blistering accompanied by skin inflammation. However, whether BP180 is involved in skin inflammation remains unknown. To address this question, we generated a BP180-dysfunctional mouse strain and found that mice lacking functional BP180 (termed ΔNC16A) developed spontaneous skin inflammatory disease, characterized by severe itch, defective skin barrier, infiltrating immune cells, elevated serum IgE levels, and increased expression of thymic stromal lymphopoietin (TSLP). Severe itch is independent of adaptive immunity and histamine, but dependent on increased expression of TSLP by keratinocytes. In addition, a high TSLP expression is detected in BP patients. Our data provide direct evidence showing that BP180 regulates skin inflammation independently of adaptive immunity, and BP180 dysfunction leads to a TSLP-mediated itch. The newly developed mouse strain could be a model for elucidation of disease mechanisms and development of novel therapeutic strategies for skin inflammation and BP180-related skin conditions.}, } @article {pmid29866843, year = {2018}, author = {De Vadder, F and Grasset, E and Mannerås Holm, L and Karsenty, G and Macpherson, AJ and Olofsson, LE and Bäckhed, F}, title = {Gut microbiota regulates maturation of the adult enteric nervous system via enteric serotonin networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6458-6463}, pmid = {29866843}, issn = {1091-6490}, support = {615362//European Research Council/International ; P01 AG032959/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Enteric Nervous System/metabolism/*microbiology/*physiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Motility/physiology ; Intestine, Small/metabolism/*microbiology ; Mice ; Mice, Inbred C57BL ; Microbiota/physiology ; Neurogenesis/physiology ; Neurons/metabolism/microbiology ; Receptors, Serotonin, 5-HT4/metabolism ; Serotonin/*metabolism ; }, abstract = {The enteric nervous system (ENS) is crucial for essential gastrointestinal physiologic functions such as motility, fluid secretion, and blood flow. The gut is colonized by trillions of bacteria that regulate host production of several signaling molecules including serotonin (5-HT) and other hormones and neurotransmitters. Approximately 90% of 5-HT originates from the intestine, and activation of the 5-HT4 receptor in the ENS has been linked to adult neurogenesis and neuroprotection. Here, we tested the hypothesis that the gut microbiota could induce maturation of the adult ENS through release of 5-HT and activation of 5-HT4 receptors. Colonization of germ-free mice with a microbiota from conventionally raised mice modified the neuroanatomy of the ENS and increased intestinal transit rates, which was associated with neuronal and mucosal 5-HT production and the proliferation of enteric neuronal progenitors in the adult intestine. Pharmacological modulation of the 5-HT4 receptor, as well as depletion of endogenous 5-HT, identified a mechanistic link between the gut microbiota and maturation of the adult ENS through the release of 5-HT and activation of the 5-HT4 receptor. Taken together, these findings show that the microbiota modulates the anatomy of the adult ENS in a 5-HT-dependent fashion with concomitant changes in intestinal transit.}, } @article {pmid29866842, year = {2018}, author = {Jung, SR and Deng, Y and Kushmerick, C and Asbury, CL and Hille, B and Koh, DS}, title = {Minimizing ATP depletion by oxygen scavengers for single-molecule fluorescence imaging in live cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5706-E5715}, pmid = {29866842}, issn = {1091-6490}, support = {R01 GM083913/GM/NIGMS NIH HHS/United States ; R01 NS008174/NS/NINDS NIH HHS/United States ; P01 GM105537/GM/NIGMS NIH HHS/United States ; R01 DK080840/DK/NIDDK NIH HHS/United States ; R01 GM079373/GM/NIGMS NIH HHS/United States ; R37 NS008174/NS/NINDS NIH HHS/United States ; S10 RR026406/RR/NCRR NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/*metabolism ; Carbocyanines/metabolism ; Cell Line ; Flavin-Adenine Dinucleotide/analogs & derivatives/metabolism ; Fluorescence ; Fluorescent Dyes/metabolism ; Glucose Oxidase/metabolism ; Glutamine/metabolism ; HEK293 Cells ; Humans ; Keto Acids/metabolism ; Microscopy, Fluorescence/methods ; Mitochondria/metabolism ; NAD/metabolism ; Oxygen/*metabolism ; Phosphatidylinositol 4,5-Diphosphate/metabolism ; Photobleaching ; Receptor, PAR-2/metabolism ; }, abstract = {The stability of organic dyes against photobleaching is critical in single-molecule tracking and localization microscopy. Since oxygen accelerates photobleaching of most organic dyes, glucose oxidase is commonly used to slow dye photobleaching by depleting oxygen. As demonstrated here, pyranose-2-oxidase slows bleaching of Alexa647 dye by ∼20-fold. However, oxygen deprivation may pose severe problems for live cells by reducing mitochondrial oxidative phosphorylation and ATP production. We formulate a method to sustain intracellular ATP levels in the presence of oxygen scavengers. Supplementation with metabolic intermediates including glyceraldehyde, glutamine, and α-ketoisocaproate maintained the intracellular ATP level for at least 10 min by balancing between FADH2 and NADH despite reduced oxygen levels. Furthermore, those metabolites supported ATP-dependent synthesis of phosphatidylinositol 4,5-bisphosphate and internalization of PAR2 receptors. Our method is potentially relevant to other circumstances that involve acute drops of oxygen levels, such as ischemic damage in the brain or heart or tissues for transplantation.}, } @article {pmid29866841, year = {2018}, author = {Tanabe, K and Ang, CE and Chanda, S and Olmos, VH and Haag, D and Levinson, DF and Südhof, TC and Wernig, M}, title = {Transdifferentiation of human adult peripheral blood T cells into neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6470-6475}, pmid = {29866841}, issn = {1091-6490}, support = {R01 MH092931/MH/NIMH NIH HHS/United States ; U19 MH104172/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Cell Differentiation/*physiology ; Cell Transdifferentiation/*physiology ; Cellular Reprogramming/physiology ; Female ; Fibroblasts/cytology ; Humans ; Induced Pluripotent Stem Cells/cytology ; Leukocytes, Mononuclear/*cytology ; Male ; Middle Aged ; Neurons/*cytology ; T-Lymphocytes/*cytology ; Young Adult ; }, abstract = {Human cell models for disease based on induced pluripotent stem (iPS) cells have proven to be powerful new assets for investigating disease mechanisms. New insights have been obtained studying single mutations using isogenic controls generated by gene targeting. Modeling complex, multigenetic traits using patient-derived iPS cells is much more challenging due to line-to-line variability and technical limitations of scaling to dozens or more patients. Induced neuronal (iN) cells reprogrammed directly from dermal fibroblasts or urinary epithelia could be obtained from many donors, but such donor cells are heterogeneous, show interindividual variability, and must be extensively expanded, which can introduce random mutations. Moreover, derivation of dermal fibroblasts requires invasive biopsies. Here we show that human adult peripheral blood mononuclear cells, as well as defined purified T lymphocytes, can be directly converted into fully functional iN cells, demonstrating that terminally differentiated human cells can be efficiently transdifferentiated into a distantly related lineage. T cell-derived iN cells, generated by nonintegrating gene delivery, showed stereotypical neuronal morphologies and expressed multiple pan-neuronal markers, fired action potentials, and were able to form functional synapses. These cells were stable in the absence of exogenous reprogramming factors. Small molecule addition and optimized culture systems have yielded conversion efficiencies of up to 6.2%, resulting in the generation of >50,000 iN cells from 1 mL of peripheral blood in a single step without the need for initial expansion. Thus, our method allows the generation of sufficient neurons for experimental interrogation from a defined, homogeneous, and readily accessible donor cell population.}, } @article {pmid29866840, year = {2018}, author = {de Semir, D and Bezrookove, V and Nosrati, M and Dar, AA and Wu, C and Shen, J and Rieken, C and Venkatasubramanian, M and Miller, JR and Desprez, PY and McAllister, S and Soroceanu, L and Debs, RJ and Salomonis, N and Schadendorf, D and Cleaver, JE and Kashani-Sabet, M}, title = {PHIP as a therapeutic target for driver-negative subtypes of melanoma, breast, and lung cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5766-E5775}, pmid = {29866840}, issn = {1091-6490}, support = {R01 CA114337/CA/NCI NIH HHS/United States ; R01 CA175768/CA/NCI NIH HHS/United States ; R01 CA215755/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Breast/*metabolism ; Carcinoma, Non-Small-Cell Lung/metabolism ; Cell Line, Tumor ; Cell Proliferation/physiology ; Cyclin D1/metabolism ; Female ; Gene Expression Regulation, Neoplastic/physiology ; Humans ; Intracellular Signaling Peptides and Proteins/*metabolism ; Lung Neoplasms/*metabolism ; Melanoma/*metabolism ; Pleckstrin Homology Domains/*physiology ; Proto-Oncogene Proteins c-akt/metabolism ; Triple Negative Breast Neoplasms/*metabolism ; }, abstract = {The identification and targeting of key molecular drivers of melanoma and breast and lung cancer have substantially improved their therapy. However, subtypes of each of these three common, lethal solid tumors lack identified molecular drivers, and are thus not amenable to targeted therapies. Here we show that pleckstrin homology domain-interacting protein (PHIP) promotes the progression of these "driver-negative" tumors. Suppression of PHIP expression significantly inhibited both tumor cell proliferation and invasion, coordinately suppressing phosphorylated AKT, cyclin D1, and talin1 expression in all three tumor types. Furthermore, PHIP's targetable bromodomain is functional, as it specifically binds the histone modification H4K91ac. Analysis of TCGA profiling efforts revealed PHIP overexpression in triple-negative and basal-like breast cancer, as well as in the bronchioid subtype of nonsmall cell lung cancer. These results identify a role for PHIP in the progression of melanoma and breast and lung cancer subtypes lacking identified targeted therapies. The use of selective, anti-PHIP bromodomain inhibitors may thus yield a broad-based, molecularly targeted therapy against currently nontargetable tumors.}, } @article {pmid29866839, year = {2018}, author = {Bourgine, PE and Klein, T and Paczulla, AM and Shimizu, T and Kunz, L and Kokkaliaris, KD and Coutu, DL and Lengerke, C and Skoda, R and Schroeder, T and Martin, I}, title = {In vitro biomimetic engineering of a human hematopoietic niche with functional properties.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5688-E5695}, pmid = {29866839}, issn = {1091-6490}, mesh = {Biomimetics/methods ; Bioreactors ; Bone Marrow/physiology ; Bone Marrow Cells/*cytology ; Cell Culture Techniques/methods ; Extracellular Matrix/physiology ; Hematopoiesis/*physiology ; Hematopoietic Stem Cells/*cytology ; Humans ; Stem Cell Niche/*physiology ; Stem Cells/*cytology ; Tissue Engineering/methods ; }, abstract = {In adults, human hematopoietic stem and progenitor cells (HSPCs) reside in the bone marrow (BM) microenvironment. Our understanding of human hematopoiesis and the associated niche biology remains limited, due to human material accessibility and limits of existing in vitro culture models. The establishment of an in vitro BM system would offer an experimentally accessible and tunable platform to study human hematopoiesis. Here, we develop a 3D engineered human BM analog by recapitulating some of the hematopoietic niche elements. This includes a bone-like scaffold, functionalized by human stromal and osteoblastic cells and by the extracellular matrix they deposited during perfusion culture in bioreactors. The resulting tissue exhibited compositional and structural features of human BM while supporting the maintenance of HSPCs. This was associated with a compartmentalization of phenotypes in the bioreactor system, where committed blood cells are released into the liquid phase and HSPCs preferentially reside within the engineered BM tissue, establishing physical interactions with the stromal compartment. Finally, we demonstrate the possibility to perturb HSPCs' behavior within our 3D niches by molecular customization or injury simulation. The developed system enables the design of advanced, tunable in vitro BM proxies for the study of human hematopoiesis.}, } @article {pmid29866838, year = {2018}, author = {Margulis, K and Chiou, AS and Aasi, SZ and Tibshirani, RJ and Tang, JY and Zare, RN}, title = {Distinguishing malignant from benign microscopic skin lesions using desorption electrospray ionization mass spectrometry imaging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6347-6352}, pmid = {29866838}, issn = {1091-6490}, mesh = {Biomarkers, Tumor ; Carcinoma, Basal Cell/*diagnosis ; Humans ; Lipids/chemistry ; Mohs Surgery/methods ; Molecular Imaging/*methods ; Neoplasms ; Protein Aggregates/physiology ; Skin Neoplasms/diagnosis ; Spectrometry, Mass, Electrospray Ionization/*methods ; }, abstract = {Detection of microscopic skin lesions presents a considerable challenge in diagnosing early-stage malignancies as well as in residual tumor interrogation after surgical intervention. In this study, we established the capability of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) to distinguish between micrometer-sized tumor aggregates of basal cell carcinoma (BCC), a common skin cancer, and normal human skin. We analyzed 86 human specimens collected during Mohs micrographic surgery for BCC to cross-examine spatial distributions of numerous lipids and metabolites in BCC aggregates versus adjacent skin. Statistical analysis using the least absolute shrinkage and selection operation (Lasso) was employed to categorize each 200-µm-diameter picture element (pixel) of investigated skin tissue map as BCC or normal. Lasso identified 24 molecular ion signals, which are significant for pixel classification. These ion signals included lipids observed at m/z 200-1,200 and Krebs cycle metabolites observed at m/z < 200. Based on these features, Lasso yielded an overall 94.1% diagnostic accuracy pixel by pixel of the skin map compared with histopathological evaluation. We suggest that DESI-MSI/Lasso analysis can be employed as a complementary technique for delineation of microscopic skin tumors.}, } @article {pmid29866837, year = {2018}, author = {Meyers, SR and Malinverno, A}, title = {Proterozoic Milankovitch cycles and the history of the solar system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6363-6368}, pmid = {29866837}, issn = {1091-6490}, abstract = {The geologic record of Milankovitch climate cycles provides a rich conceptual and temporal framework for evaluating Earth system evolution, bestowing a sharp lens through which to view our planet's history. However, the utility of these cycles for constraining the early Earth system is hindered by seemingly insurmountable uncertainties in our knowledge of solar system behavior (including Earth-Moon history), and poor temporal control for validation of cycle periods (e.g., from radioisotopic dates). Here we address these problems using a Bayesian inversion approach to quantitatively link astronomical theory with geologic observation, allowing a reconstruction of Proterozoic astronomical cycles, fundamental frequencies of the solar system, the precession constant, and the underlying geologic timescale, directly from stratigraphic data. Application of the approach to 1.4-billion-year-old rhythmites indicates a precession constant of 85.79 ± 2.72 arcsec/year (2σ), an Earth-Moon distance of 340,900 ± 2,600 km (2σ), and length of day of 18.68 ± 0.25 hours (2σ), with dominant climatic precession cycles of ∼14 ky and eccentricity cycles of ∼131 ky. The results confirm reduced tidal dissipation in the Proterozoic. A complementary analysis of Eocene rhythmites (∼55 Ma) illustrates how the approach offers a means to map out ancient solar system behavior and Earth-Moon history using the geologic archive. The method also provides robust quantitative uncertainties on the eccentricity and climatic precession periods, and derived astronomical timescales. As a consequence, the temporal resolution of ancient Earth system processes is enhanced, and our knowledge of early solar system dynamics is greatly improved.}, } @article {pmid29866836, year = {2018}, author = {Frank, KT and Petrie, B and Leggett, WC and Boyce, DG}, title = {Exploitation drives an ontogenetic-like deepening in marine fish.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6422-6427}, pmid = {29866836}, issn = {1091-6490}, mesh = {Animals ; Biological Ontologies ; Fisheries ; Fishes/*physiology ; Gadus morhua ; North Sea ; Population Dynamics ; Seafood ; }, abstract = {Virtually all studies reporting deepening with increasing size or age by fishes involve commercially harvested species. Studies of North Sea plaice in the early 1900s first documented this phenomenon (named Heincke's law); it occurred at a time of intensive harvesting and rapid technological changes in fishing methods. The possibility that this deepening might be the result of harvesting has never been evaluated. Instead, age- or size-related deepening have been credited to interactions between density-dependent food resources and density-independent environmental factors. Recently, time-dependent depth variations have been ascribed to ocean warming. We use a model, initialized from observations of Atlantic cod (Gadus morhua) on the eastern Scotian Shelf, where an age-dependent deepening of ∼60 m was observed, to assess the effect of size- and depth-selective exploitation on fish distribution. Exploitation restricted to the upper 80 m can account for ∼72% of the observed deepening; by extending exploitation to 120 m, all of the deepening can be accounted for. In the absence of fishing, the model indicated no age-related deepening. Observations of depth distributions of older cod during a moratorium on fishing supported this prediction; however, younger cod exhibited low-amplitude deepening (10-15 m) suggestive of an ontogenetic response. The implications of these findings are manifold, particularly as they relate to hypotheses advanced to explain the ecological and evolutionary basis for ontogenetic deepening and to recent calls for the adoption of evidence of species deepening as a biotic indicator or "footprint" of warming seas.}, } @article {pmid29866835, year = {2018}, author = {Wu, S and He, Y and Qiu, X and Yang, W and Liu, W and Li, X and Li, Y and Shen, HM and Wang, R and Yue, Z and Zhao, Y}, title = {Targeting the potent Beclin 1-UVRAG coiled-coil interaction with designed peptides enhances autophagy and endolysosomal trafficking.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5669-E5678}, pmid = {29866835}, issn = {1091-6490}, support = {R01 NS060123/NS/NINDS NIH HHS/United States ; }, mesh = {A549 Cells ; Amino Acid Sequence ; Autophagy/*physiology ; Beclin-1/*metabolism ; Cell Line ; Cell Line, Tumor ; Endosomes/*metabolism/physiology ; ErbB Receptors/metabolism ; HEK293 Cells ; Humans ; Lysosomes/*metabolism/physiology ; Peptides/*metabolism ; Protein Domains/physiology ; Protein Interaction Domains and Motifs/*physiology ; Protein Transport/*physiology ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {The Beclin 1-Vps34 complex, known as "mammalian class III PI3K," plays essential roles in membrane-mediated transport processes including autophagy and endosomal trafficking. Beclin 1 acts as a scaffolding molecule for the complex and readily transits from its metastable homodimeric state to interact with key modulators such as Atg14L or UVRAG and form functionally distinct Atg14L/UVRAG-containing Beclin 1-Vps34 subcomplexes. The Beclin 1-Atg14L/UVRAG interaction relies critically on their coiled-coil domains, but the molecular mechanism remains poorly understood. We determined the crystal structure of Beclin 1-UVRAG coiled-coil complex and identified a strengthened interface with both hydrophobic pairings and electrostatically complementary interactions. This structure explains why the Beclin 1-UVRAG interaction is more potent than the metastable Beclin 1 homodimer. Potent Beclin 1-UVRAG interaction is functionally significant because it renders UVRAG more competitive than Atg14L in Beclin 1 binding and is critical for promoting endolysosomal trafficking. UVRAG coiled-coil mutants with weakened Beclin 1 binding do not outcompete Atg14L and fail to promote endolysosomal degradation of the EGF receptor (EGFR). We designed all-hydrocarbon stapled peptides that specifically targeted the C-terminal part of the Beclin 1 coiled-coil domain to interfere with its homodimerization. One such peptide reduced Beclin 1 self-association, promoted Beclin 1-Atg14L/UVRAG interaction, increased autophagic flux, and enhanced EGFR degradation. Our results demonstrate that the targeting Beclin 1 coiled-coil domain with designed peptides to induce the redistribution of Beclin 1 among its self-associated form or Atg14L/UVRAG-containing complexes enhances both autophagy and endolysosomal trafficking.}, } @article {pmid29866834, year = {2018}, author = {Holroyd, CB and Ribas-Fernandes, JJF and Shahnazian, D and Silvetti, M and Verguts, T}, title = {Human midcingulate cortex encodes distributed representations of task progress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6398-6403}, pmid = {29866834}, issn = {1091-6490}, mesh = {Adult ; Brain/*physiology ; Brain Mapping/methods ; Cognition/physiology ; Female ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Neurons/physiology ; Photic Stimulation/methods ; Psychomotor Performance/*physiology ; Young Adult ; }, abstract = {The function of midcingulate cortex (MCC) remains elusive despite decades of investigation and debate. Complicating matters, individual MCC neurons respond to highly diverse task-related events, and MCC activation is reported in most human neuroimaging studies employing a wide variety of task manipulations. Here we investigate this issue by applying a model-based cognitive neuroscience approach involving neural network simulations, functional magnetic resonance imaging, and representational similarity analysis. We demonstrate that human MCC encodes distributed, dynamically evolving representations of extended, goal-directed action sequences. These representations are uniquely sensitive to the stage and identity of each sequence, indicating that MCC sustains contextual information necessary for discriminating between task states. These results suggest that standard univariate approaches for analyzing MCC function overlook the major portion of task-related information encoded by this brain area and point to promising new avenues for investigation.}, } @article {pmid29866833, year = {2018}, author = {Hu, YC and Li, YW and Yang, Y and Guan, PF and Bai, HY and Wang, WH}, title = {Configuration correlation governs slow dynamics of supercooled metallic liquids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6375-6380}, pmid = {29866833}, issn = {1091-6490}, abstract = {The origin of dramatic slowing down of dynamics in metallic glass-forming liquids toward their glass transition temperatures is a fundamental but unresolved issue. Through extensive molecular dynamics simulations, here we show that, contrary to the previous beliefs, it is not local geometrical orderings extracted from instantaneous configurations but the intrinsic correlation between configurations that captures the structural origin governing slow dynamics. More significantly, it is demonstrated by scaling analyses that it is the correlation length extracted from configuration correlation rather than dynamic correlation lengths that is the key to determine the drastic slowdown of supercooled metallic liquids. The key role of the configuration correlation established here sheds important light on the structural origin of the mysterious glass transition and provides an essential piece of the puzzle for the development of a universal theoretical understanding of glass transition in glasses.}, } @article {pmid29866832, year = {2018}, author = {Swift, JA and Roberts, P and Boivin, N and Kirch, PV}, title = {Restructuring of nutrient flows in island ecosystems following human colonization evidenced by isotopic analysis of commensal rats.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6392-6397}, pmid = {29866832}, issn = {1091-6490}, mesh = {Animals ; Carbon/chemistry ; Ecosystem ; Food ; Food Chain ; Humans ; Nitrogen Isotopes/*analysis/*chemistry ; Pacific Islands ; Rats ; }, abstract = {The role of humans in shaping local ecosystems is an increasing focus of archaeological research, yet researchers often lack an appropriate means of measuring past anthropogenic effects on local food webs and nutrient cycling. Stable isotope analysis of commensal animals provides an effective proxy for local human environments because these species are closely associated with human activities without being under direct human management. Such species are thus central to nutrient flows across a range of socionatural environments and can provide insight into how they intersected and transformed over time. Here we measure and compare stable carbon and nitrogen isotope data from Pacific rat (Rattus exulans) skeletal remains across three Polynesian island systems [Mangareva, Ua Huka (Marquesas), and the Polynesian Outlier of Tikopia] during one of the most significant cases of human migration and commensal introduction in prehistory. The results demonstrate widespread δ15N declines across these islands that are associated with human land use, intensification, and faunal community restructuring. Local comparison of rat stable isotope data also tracks human activities and resource availability at the level of the settlement. Our results highlight the large-scale restructuring of nutrient flows in island ecosystems that resulted from human colonization and ecosystem engineering activities on Pacific islands. They also demonstrate that stable isotope analysis of often-ignored commensal taxa can provide a tool for tracking human land use and environmental effects.}, } @article {pmid29866831, year = {2018}, author = {Martinière, A and Gibrat, R and Sentenac, H and Dumont, X and Gaillard, I and Paris, N}, title = {Uncovering pH at both sides of the root plasma membrane interface using noninvasive imaging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6488-6493}, pmid = {29866831}, issn = {1091-6490}, mesh = {Arabidopsis/metabolism/physiology ; Arabidopsis Proteins/metabolism ; Biological Transport/physiology ; Cell Membrane/metabolism/*physiology ; Cell Wall/physiology ; Homeostasis/physiology ; Hydrogen-Ion Concentration ; Plant Roots/metabolism/*physiology ; }, abstract = {Building a proton gradient across a biological membrane and between different tissues is a matter of great importance for plant development and nutrition. To gain a better understanding of proton distribution in the plant root apoplast as well as across the plasma membrane, we generated Arabidopsis plants expressing stable membrane-anchored ratiometric fluorescent sensors based on pHluorin. These sensors enabled noninvasive pH-specific measurements in mature root cells from the medium-epidermis interface up to the inner cell layers that lie beyond the Casparian strip. The membrane-associated apoplastic pH was much more alkaline than the overall apoplastic space pH. Proton concentration associated with the plasma membrane was very stable, even when the growth medium pH was altered. This is in apparent contradiction with the direct connection between root intercellular space and the external medium. The plasma membrane-associated pH in the stele was the most preserved and displayed the lowest apoplastic pH (6.0 to 6.1) and the highest transmembrane delta pH (1.5 to 2.2). Both pH values also correlated well with optimal activities of channels and transporters involved in ion uptake and redistribution from the root to the aerial part. In growth medium where ionic content is minimized, the root plasma membrane-associated pH was more affected by environmental proton changes, especially for the most external cell layers. Calcium concentration appears to play a major role in apoplastic pH under these restrictive conditions, supporting a role for the cell wall in pH homeostasis of the unstirred surface layer of plasma membrane in mature roots.}, } @article {pmid29866830, year = {2018}, author = {Pandeya, D and López-Arredondo, DL and Janga, MR and Campbell, LM and Estrella-Hernández, P and Bagavathiannan, MV and Herrera-Estrella, L and Rathore, KS}, title = {Selective fertilization with phosphite allows unhindered growth of cotton plants expressing the ptxD gene while suppressing weeds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {29}, pages = {E6946-E6955}, pmid = {29866830}, issn = {1091-6490}, mesh = {*Bacterial Proteins/biosynthesis/genetics ; *Fertilizers ; *Gene Expression ; *Gossypium/enzymology/genetics/growth & development ; Phosphites/*pharmacology ; *Plants, Genetically Modified/enzymology/genetics/growth & development ; *Transcription Factors/biosynthesis/genetics ; Weed Control/*methods ; }, abstract = {Weeds, which have been the bane of agriculture since the beginning of civilization, are managed manually, mechanically, and, more recently, by chemicals. However, chemical control options are rapidly shrinking due to the recent rise in the number of herbicide-resistant weeds in crop fields, with few alternatives on the horizon. Therefore, there is an urgent need for alternative weed suppression systems to sustain crop productivity while reducing our dependence on herbicides and tillage. Such a development will also allay some of the negative perceptions associated with the use of herbicide-resistance genes and heavy dependence on herbicides. Transgenic plants expressing the bacterial phosphite dehydrogenase (ptxD) gene gain an ability to convert phosphite (Phi) into orthophosphate [Pi, the metabolizable form of phosphorus (P)]. Such plants allow for a selective fertilization scheme, based on Phi as the sole source of P for the crop, while offering an effective alternative for suppressing weed growth. Here, we show that, when P is supplied in the form of Phi, ptxD-expressing cotton (Gossypium hirsutum L.) plants outcompete, in both artificial substrates and natural soils from agricultural fields, three different monocot and dicot weed species intentionally introduced in the experiments, as well as weeds naturally present in the tested soils. Importantly, the ptxD/Phi system proved highly efficacious in inhibiting the growth of glyphosate-resistant Palmer amaranth. With over 250 weed species resistant to currently available herbicides, ptxD-transgenic plants fertilized with Phi could provide an effective alternative to suppressing the growth of these weeds while providing adequate nutrition to the crop.}, } @article {pmid29866829, year = {2018}, author = {Mackenbach, JP and Valverde, JR and Artnik, B and Bopp, M and Brønnum-Hansen, H and Deboosere, P and Kalediene, R and Kovács, K and Leinsalu, M and Martikainen, P and Menvielle, G and Regidor, E and Rychtaříková, J and Rodriguez-Sanz, M and Vineis, P and White, C and Wojtyniak, B and Hu, Y and Nusselder, WJ}, title = {Trends in health inequalities in 27 European countries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6440-6445}, pmid = {29866829}, issn = {1091-6490}, mesh = {Adult ; Aged ; Economic Recession/statistics & numerical data ; Europe ; Female ; Health Status Disparities ; Healthcare Disparities/*economics/*statistics & numerical data ; Humans ; Interrupted Time Series Analysis/statistics & numerical data ; Male ; Middle Aged ; Self Report ; Self-Assessment ; Socioeconomic Factors ; }, abstract = {Unfavorable health trends among the lowly educated have recently been reported from the United States. We analyzed health trends by education in European countries, paying particular attention to the possibility of recent trend interruptions, including interruptions related to the impact of the 2008 financial crisis. We collected and harmonized data on mortality from ca 1980 to ca 2014 for 17 countries covering 9.8 million deaths and data on self-reported morbidity from ca 2002 to ca 2014 for 27 countries covering 350,000 survey respondents. We used interrupted time-series analyses to study changes over time and country-fixed effects analyses to study the impact of crisis-related economic conditions on health outcomes. Recent trends were more favorable than in previous decades, particularly in Eastern Europe, where mortality started to decline among lowly educated men and where the decline in less-than-good self-assessed health accelerated, resulting in some narrowing of health inequalities. In Western Europe, mortality has continued to decline among the lowly and highly educated, and although the decline of less-than-good self-assessed health slowed in countries severely hit by the financial crisis, this affected lowly and highly educated equally. Crisis-related economic conditions were not associated with widening health inequalities. Our results show that the unfavorable trends observed in the United States are not found in Europe. There has also been no discernible short-term impact of the crisis on health inequalities at the population level. Both findings suggest that European countries have been successful in avoiding an aggravation of health inequalities.}, } @article {pmid29866828, year = {2018}, author = {Wang, CY and Patel, N and Wholey, WY and Dawid, S}, title = {ABC transporter content diversity in Streptococcus pneumoniae impacts competence regulation and bacteriocin production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5776-E5785}, pmid = {29866828}, issn = {1091-6490}, support = {R01 AI101285/AI/NIAID NIH HHS/United States ; T32 AI007528/AI/NIAID NIH HHS/United States ; T32 GM007863/GM/NIGMS NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/*metabolism ; Animals ; Bacterial Proteins/*metabolism ; Bacteriocins/*metabolism ; Female ; Gene Expression Regulation, Bacterial/physiology ; Membrane Transport Proteins/metabolism ; Mice ; Mice, Inbred BALB C ; Nasopharynx/metabolism/microbiology ; Pheromones/metabolism ; Streptococcus pneumoniae/*metabolism ; }, abstract = {The opportunistic pathogen Streptococcus pneumoniae (pneumococcus) uses natural genetic competence to increase its adaptability through horizontal gene transfer. One method of acquiring DNA is through predation of neighboring strains with antimicrobial peptides called "bacteriocins." Competence and production of the major family of pneumococcal bacteriocins, pneumocins, are regulated by the quorum-sensing systems com and blp, respectively. In the classical paradigm, the ABC transporters ComAB and BlpAB each secretes its own system's signaling pheromone and in the case of BlpAB also secretes the pneumocins. While ComAB is found in all pneumococci, only 25% of strains encode an intact version of BlpAB [BlpAB(+)] while the rest do not [BlpAB(-)]. Contrary to the classical paradigm, it was previously shown that BlpAB(-) strains can activate blp through ComAB-mediated secretion of the blp pheromone during brief periods of competence. To better understand the full extent of com-blp crosstalk, we examined the contribution of each transporter to competence development and pneumocin secretion. We found that BlpAB(+) strains have a greater capacity for competence activation through BlpAB-mediated secretion of the com pheromone. Similarly, we show that ComAB and BlpAB are promiscuous and both can secrete pneumocins. Consequently, differences in pneumocin secretion between BlpAB(+) and BlpAB(-) strains derive from the regulation and kinetics of transporter expression rather than substrate specificity. We speculate that BlpAB(-) strains (opportunists) use pneumocins mainly in a narrowly tailored role for DNA acquisition and defense during competence while BlpAB(+) strains (aggressors) expand their use for the general inhibition of rival strains.}, } @article {pmid29866827, year = {2018}, author = {Mittal, S and Yeh, K and Leslie, LS and Kenkel, S and Kajdacsy-Balla, A and Bhargava, R}, title = {Simultaneous cancer and tumor microenvironment subtyping using confocal infrared microscopy for all-digital molecular histopathology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5651-E5660}, pmid = {29866827}, issn = {1091-6490}, support = {R01 EB009745/EB/NIBIB NIH HHS/United States ; T32 EB019944/EB/NIBIB NIH HHS/United States ; }, mesh = {Algorithms ; Breast/physiology ; Breast Neoplasms/*pathology ; Humans ; Lasers, Semiconductor ; Microscopy, Confocal/*methods ; Spectroscopy, Fourier Transform Infrared/*methods ; Tumor Microenvironment/*physiology ; }, abstract = {Histopathology based on spatial patterns of epithelial cells is the gold standard for clinical diagnoses and research in carcinomas; although known to be important, the tissue microenvironment is not readily used due to complex and subjective interpretation with existing tools. Here, we demonstrate accurate subtyping from molecular properties of epithelial cells using emerging high-definition Fourier transform infrared (HD FT-IR) spectroscopic imaging combined with machine learning algorithms. In addition to detecting four epithelial subtypes, we simultaneously delineate three stromal subtypes that characterize breast tumors. While FT-IR imaging data enable fully digital pathology with rich information content, the long spectral scanning times required for signal averaging and processing make the technology impractical for routine research or clinical use. Hence, we developed a confocal design in which refractive IR optics are designed to provide high-definition, rapid spatial scanning and discrete spectral tuning using a quantum cascade laser (QCL) source. This instrument provides simultaneously high resolving power (2-μm pixel size) and high signal-to-noise ratio (SNR) (>1,300), providing a speed increase of ∼50-fold for obtaining classified results compared with present imaging spectrometers. We demonstrate spectral fidelity and interinstrument operability of our developed instrument by accurate analysis of a 100-case breast tissue set that was analyzed in a day, considerably speeding research. Clinical breast biopsies typical of a patients' caseload are analyzed in ∼1 hour. This study paves the way for comprehensive tumor-microenvironment analyses in feasible time periods, presenting a critical step in practical label-free molecular histopathology.}, } @article {pmid29866826, year = {2018}, author = {Castanotto, D and Zhang, X and Alluin, J and Zhang, X and Rüger, J and Armstrong, B and Rossi, J and Riggs, A and Stein, CA}, title = {A stress-induced response complex (SIRC) shuttles miRNAs, siRNAs, and oligonucleotides to the nucleus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5756-E5765}, pmid = {29866826}, issn = {1091-6490}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; }, mesh = {Active Transport, Cell Nucleus/physiology ; Cell Line ; Cell Line, Tumor ; Cell Nucleus/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; MicroRNAs/*metabolism ; Oligonucleotides/*metabolism ; RNA, Small Interfering/*metabolism ; Transcription, Genetic/physiology ; }, abstract = {Although some information is available for specific subsets of miRNAs and several factors have been shown to bind oligonucleotides (ONs), no general transport mechanism for these molecules has been identified to date. In this work, we demonstrate that the nuclear transport of ONs, siRNAs, and miRNAs responds to cellular stress. Furthermore, we have identified a stress-induced response complex (SIRC), which includes Ago-1 and Ago-2 in addition to the transcription and splicing regulators YB1, CTCF, FUS, Smad1, Smad3, and Smad4. The SIRC transports endogenous miRNAs, siRNAs, and ONs to the nucleus. We show that cellular stress can significantly increase ON- or siRNA-directed splicing switch events and endogenous miRNA targeting of nuclear RNAs.}, } @article {pmid29866825, year = {2018}, author = {Fang, M and Bauer, CE}, title = {Regulation of stringent factor by branched-chain amino acids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6446-6451}, pmid = {29866825}, issn = {1091-6490}, support = {R01 GM040941/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Amino Acids, Branched-Chain/*metabolism ; Bacterial Proteins/metabolism ; Guanosine Diphosphate/metabolism ; Guanosine Triphosphate/metabolism ; Hydrolases/metabolism ; Ligases/metabolism ; Rhodobacter capsulatus/metabolism ; }, abstract = {When faced with amino acid starvation, prokaryotic cells induce a stringent response that modulates their physiology. The stringent response is manifested by production of signaling molecules guanosine 5'-diphosphate,3'-diphosphate (ppGpp) and guanosine 5'-triphosphate,3'-diphosphate (pppGpp) that are also called alarmones. In many species, alarmone levels are regulated by a multidomain bifunctional alarmone synthetase/hydrolase called Rel. In this enzyme, there is an ACT domain at the carboxyl region that has an unknown function; however, similar ACT domains are present in other enzymes that have roles in controlling amino acid metabolism. In many cases, these other ACT domains have been shown to allosterically regulate enzyme activity through the binding of amino acids. Here, we show that the ACT domain present in the Rhodobacter capsulatus Rel alarmone synthetase/hydrolase binds branched-chain amino acids valine and isoleucine. We further show that the binding of these amino acids stimulates alarmone hydrolase activity both in vitro and in vivo. Furthermore, we found that the ACT domain present in Rel proteins from many diverse species also binds branched-chain amino acids. These results indicate that the cellular concentration of amino acids can directly affect Rel alarmone synthetase/hydrolase activity, thus adding another layer of control to current models of cellular control of the stringent response.}, } @article {pmid29866824, year = {2018}, author = {Doctrow, B}, title = {QnAs with Mark Hay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6521-6522}, pmid = {29866824}, issn = {1091-6490}, mesh = {Animals ; Anthozoa/physiology ; Aquatic Organisms/*physiology ; *Awards and Prizes ; Climate Change ; Conservation of Natural Resources ; *Coral Reefs ; Extinction, Biological ; Feeding Behavior ; Fiji ; Fisheries ; Fishes/physiology ; Human Activities ; Humans ; *Marine Biology ; Pheromones/isolation & purification/*physiology ; Phytochemicals/isolation & purification ; Seaweed/physiology ; Species Specificity ; }, } @article {pmid29866823, year = {2018}, author = {Zhang, S and van der Laan, G and Müller, J and Heinen, L and Garst, M and Bauer, A and Berger, H and Pfleiderer, C and Hesjedal, T}, title = {Reciprocal space tomography of 3D skyrmion lattice order in a chiral magnet.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6386-6391}, pmid = {29866823}, issn = {1091-6490}, abstract = {It is commonly assumed that surfaces modify the properties of stable materials within the top few atomic layers of a bulk specimen only. Exploiting the polarization dependence of resonant elastic X-ray scattering to go beyond conventional diffraction and imaging techniques, we have determined the depth dependence of the full 3D spin structure of skyrmions-that is, topologically nontrivial whirls of the magnetization-below the surface of a bulk sample of Cu2OSeO3 We found that the skyrmions change exponentially from pure Néel- to pure Bloch-twisting over a distance of several hundred nanometers between the surface and the bulk, respectively. Though qualitatively consistent with theory, the strength of the Néel-twisting at the surface and the length scale of the variation observed experimentally exceed material-specific modeling substantially. In view of the exceptionally complete quantitative theoretical account of the magnetic rigidities and associated static and dynamic properties of skyrmions in Cu2OSeO3 and related materials, we conclude that subtle changes of the materials properties must exist at distances up to several hundred atomic layers into the bulk, which originate in the presence of the surface. This has far-reaching implications for the creation of skyrmions in surface-dominated systems and identifies, more generally, surface-induced gradual variations deep within a bulk material and their impact on tailored functionalities as an unchartered scientific territory.}, } @article {pmid29866822, year = {2018}, author = {Hemming, ML and Lawlor, MA and Zeid, R and Lesluyes, T and Fletcher, JA and Raut, CP and Sicinska, ET and Chibon, F and Armstrong, SA and Demetri, GD and Bradner, JE}, title = {Gastrointestinal stromal tumor enhancers support a transcription factor network predictive of clinical outcome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5746-E5755}, pmid = {29866822}, issn = {1091-6490}, support = {P01 CA066996/CA/NCI NIH HHS/United States ; }, mesh = {Basic Helix-Loop-Helix Transcription Factors/genetics ; Cell Line, Tumor ; Cell Proliferation/genetics ; Disease Progression ; Disease-Free Survival ; Gastrointestinal Stromal Tumors/*genetics/pathology ; HEK293 Cells ; Humans ; Mutation/genetics ; Proto-Oncogene Proteins c-kit/genetics ; Receptor Protein-Tyrosine Kinases/genetics ; Receptor, Platelet-Derived Growth Factor alpha/genetics ; Transcription Factors/*genetics ; }, abstract = {Activating mutations in the KIT or PDGFRA receptor tyrosine kinases are hallmarks of gastrointestinal stromal tumor (GIST). The biological underpinnings of recurrence following resection or disease progression beyond kinase mutation are poorly understood. Utilizing chromatin immunoprecipitation with sequencing of tumor samples and cell lines, we describe the enhancer landscape of GIST, highlighting genes that reinforce and extend our understanding of these neoplasms. A group of core transcription factors can be distinguished from others unique to localized and metastatic disease. The transcription factor HAND1 emerges in metastatic disease, binds to established GIST-associated enhancers, and facilitates GIST cell proliferation and KIT gene expression. The pattern of transcription factor expression in primary tumors is predictive of metastasis-free survival in GIST patients. These results provide insight into the enhancer landscape and transcription factor network underlying GIST, and define a unique strategy for predicting clinical behavior of this disease.}, } @article {pmid29866821, year = {2018}, author = {Ayuso-Fernández, I and Ruiz-Dueñas, FJ and Martínez, AT}, title = {Evolutionary convergence in lignin-degrading enzymes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6428-6433}, pmid = {29866821}, issn = {1091-6490}, mesh = {Biological Evolution ; Carbon Cycle/physiology ; Fungal Proteins/metabolism ; Fungi/metabolism ; Lignin/*metabolism ; Oxidation-Reduction ; Peroxidases/*metabolism ; Phylogeny ; Polymers/metabolism ; Polyporales/metabolism ; }, abstract = {The resurrection of ancestral enzymes of now-extinct organisms (paleogenetics) is a developing field that allows the study of evolutionary hypotheses otherwise impossible to be tested. In the present study, we target fungal peroxidases that play a key role in lignin degradation, an essential process in the carbon cycle and often a limiting step in biobased industries. Ligninolytic peroxidases are secreted by wood-rotting fungi, the origin of which was recently established in the Carboniferous period associated with the appearance of these enzymes. These first peroxidases were not able to degrade lignin directly and used diffusible metal cations to attack its phenolic moiety. The phylogenetic analysis of the peroxidases of Polyporales, the order in which most extant wood-rotting fungi are included, suggests that later in evolution these enzymes would have acquired the ability to degrade nonphenolic lignin using a tryptophanyl radical interacting with the bulky polymer at the surface of the enzyme. Here, we track this powerful strategy for lignin degradation as a phenotypic trait in fungi and show that it is not an isolated event in the evolution of Polyporales. Using ancestral enzyme resurrection, we study the molecular changes that led to the appearance of the same surface oxidation site in two distant peroxidase lineages. By characterization of the resurrected enzymes, we demonstrate convergent evolution at the amino acid level during the evolution of these fungi and track the different changes leading to phylogenetically distant ligninolytic peroxidases from ancestors lacking the ability to degrade nonphenolic lignin.}, } @article {pmid29866820, year = {2018}, author = {Boehnke, P and Bell, EA and Stephan, T and Trappitsch, R and Keller, CB and Pardo, OS and Davis, AM and Harrison, TM and Pellin, MJ}, title = {Potassic, high-silica Hadean crust.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6353-6356}, pmid = {29866820}, issn = {1091-6490}, support = {80NSSC18K0250/ImNASA/Intramural NASA/United States ; 80NSSC18K0251/ImNASA/Intramural NASA/United States ; }, abstract = {Understanding Hadean (>4 Ga) Earth requires knowledge of its crust. The composition of the crust and volatiles migrating through it directly influence the makeup of the atmosphere, the composition of seawater, and nutrient availability. Despite its importance, there is little known and less agreed upon regarding the nature of the Hadean crust. By analyzing the 87Sr/86Sr ratio of apatite inclusions in Archean zircons from Nuvvuagittuq, Canada, we show that its protolith had formed a high (>1) Rb/Sr ratio reservoir by at least 4.2 Ga. This result implies that the early crust had a broad range of igneous rocks, extending from mafic to highly silicic compositions.}, } @article {pmid29866819, year = {2018}, author = {McFarlin, JM and Axford, Y and Osburn, MR and Kelly, MA and Osterberg, EC and Farnsworth, LB}, title = {Pronounced summer warming in northwest Greenland during the Holocene and Last Interglacial.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6357-6362}, pmid = {29866819}, issn = {1091-6490}, abstract = {Projections of future rates of mass loss from the Greenland Ice Sheet are highly uncertain because its sensitivity to warming is unclear. Geologic reconstructions of Quaternary interglacials can illustrate how the ice sheet responded during past warm periods, providing insights into ice sheet behavior and important tests for data-model comparisons. However, paleoclimate records from Greenland are limited: Early Holocene peak warmth has been quantified at only a few sites, and terrestrial sedimentary records of prior interglacials are exceptionally rare due to glacial erosion during the last glacial period. Here, we discuss findings from a lacustrine archive that records both the Holocene and the Last Interglacial (LIG) from Greenland, allowing for direct comparison between two interglacials. Sedimentary chironomid assemblages indicate peak July temperatures 4.0 to 7.0 °C warmer than modern during the Early Holocene maximum in summer insolation. Chaoborus and chironomids in LIG sediments indicate July temperatures at least 5.5 to 8.5 °C warmer than modern. These estimates indicate pronounced warming in northwest Greenland during both interglacials. This helps explain dramatic ice sheet thinning at Camp Century in northwest Greenland during the Early Holocene and, for the LIG, aligns with controversial estimates of Eemian warming from ice core data retrieved in northern Greenland. Converging geologic evidence for strong LIG warming is challenging to reconcile with inferred Greenland Ice Sheet extent during the LIG, and the two appear incompatible in many models of ice sheet evolution. An increase in LIG snowfall could help resolve this problem, pointing to the need for hydroclimate reconstructions from the region.}, } @article {pmid29866473, year = {2018}, author = {Geoghegan, JA and Dufrêne, YF}, title = {Mechanomicrobiology: How Mechanical Forces Activate Staphylococcus aureus Adhesion.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {645-648}, doi = {10.1016/j.tim.2018.05.004}, pmid = {29866473}, issn = {1878-4380}, abstract = {During colonization of biomaterials and host tissues, surface-attached bacteria are subjected to mechanical stresses, including hydrodynamic flow and cell-surface contacts. Two publications show that mechanical force activates the adhesive function of Staphylococcus aureus surface proteins, thereby providing the pathogen with a means to withstand high shear stress during colonization.}, } @article {pmid29866445, year = {2018}, author = {Metz, HC and McBride, CS}, title = {Malaria Parasites Alter Human Odor to Attract Mosquito Vectors.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {547-549}, doi = {10.1016/j.pt.2018.05.003}, pmid = {29866445}, issn = {1471-5007}, mesh = {Animals ; *Anopheles ; Humans ; Malaria ; Malaria, Falciparum ; *Mosquito Vectors ; Odorants ; Parasites ; Plasmodium falciparum ; }, abstract = {Several studies have demonstrated that malaria parasites can render vertebrate hosts - including humans - more attractive to biting mosquitoes. A recent study provides evidence that Plasmodium falciparum infection alters the aldehyde composition of human foot odor, and suggests that this may be the proximate cause of increased attraction.}, } @article {pmid29866402, year = {2018}, author = {Jukola, S}, title = {On the evidentiary standards for nutrition advice.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.shpsc.2018.05.007}, pmid = {29866402}, issn = {1879-2499}, abstract = {This paper evaluates the application of evidentiary standards originating from evidence-based medicine in nutrition advice. It shows that it is problematic to criticize nutrition recommendations for not being based on randomized controlled trials. Due to practical, ethical and methodological and reasons, it is difficult to conduct rigorous randomized controlled trials for acquiring evidence that is relevant for achieving the goals of population-level nutrition recommendations. Given the non-epistemic goals of the dietary recommendations, criteria of acceptable evidence should be adapted to the goals of the practice and the practical, ethical, and methodological constraints of the situation.}, } @article {pmid29866200, year = {2018}, author = {Larsson, P and Borge, CR and Nygren-Bonnier, M and Lerdal, A and Edvardsen, A}, title = {An evaluation of the short physical performance battery following pulmonary rehabilitation in patients with chronic obstructive pulmonary disease.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {348}, pmid = {29866200}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Exercise/*physiology ; Exercise Test/*methods ; Female ; Health Status ; Humans ; Male ; Middle Aged ; Pulmonary Disease, Chronic Obstructive/*physiopathology/*rehabilitation ; Quality of Life ; Respiratory Function Tests ; }, abstract = {OBJECTIVE: There is a need for simple tools to evaluate physical performance in patients with COPD before and after pulmonary rehabilitation. The aims of this study were to evaluate changes in short physical performance battery (SPPB)-scores in patients with COPD after a 4-week pulmonary rehabilitation program; explore possible relationships between SPPB-scores and exercise capacity (6-min walk distance), dyspnea (modified Medical Research Council's dyspnea scale), disease-specific quality of life (COPD assessment test), and pulmonary function (predicted forced expiratory volume in one second) at baseline; and explore if changes in SPPB-scores are related to changes in exercise capacity, dyspnea, and disease-specific quality of life following pulmonary rehabilitation.

RESULTS: Forty-five patients with COPD were included in the final analysis. SPPB-scores improved following pulmonary rehabilitation (mean change: 1.2 ± 1.7 points, p < 0.001). There were moderate correlations between SPPB-scores and exercise capacity (r = 0.50, p < 0.001) and dyspnea (r = - 0.45, p = 0.003) at baseline, but not with pulmonary function or disease-specific quality of life. Changes in SPPB-scores were not associated with changes in exercise capacity or dyspnea scores. The SPPB may be a useful tool for evaluating physical performance in COPD Trial registration ClinicalTrials.gov NCT02314338, December 11, 2014.}, } @article {pmid29866171, year = {2018}, author = {, and , }, title = {National report on aggressions to physicians in Spain 2010-2015: violence in the workplace-ecological study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {347}, pmid = {29866171}, issn = {1756-0500}, mesh = {Adult ; Aged ; *Aggression ; Female ; Humans ; Male ; Middle Aged ; Personnel, Hospital/statistics & numerical data ; Physicians/*statistics & numerical data ; Physicians, Primary Care/statistics & numerical data ; Spain ; Surveys and Questionnaires ; Violence/*statistics & numerical data ; Workplace/*statistics & numerical data ; }, abstract = {OBJECTIVE: Aggressions against health staff is a phenomenon that is not widely studied worldwide. To date, there is no national study analyzing this situation in Spain. Our objective is to describe and analyze aggressions to physicians of the whole Spanish territory in the period 2010-2015, through an observational analytical study by conglomerates (ecological) with all aggressions to physicians identified by the 52 official medical associations of Spain over 6 years of study.

RESULTS: There were 2419 aggressions on physicians, 51% on men. Primary care is the area that concentrates more incidents (54%) and the public sector is the most affected (89%). A third of the assaults were concentrated on professionals aged 46-55 years old. Cumulative incidence decreased from 20 aggressions × 10,000 physicians in 2010 to 15 × 10,000 physicians in 2015. The importance and seriousness of the problem of aggressions against physicians is verified through notifications to the registry. The collection method is different from others based on surveys, and therefore the figures are significantly lower than other studies. The scant denunciation by attacked physicians in Spain makes deceiving the real dimensions of the phenomenon.}, } @article {pmid29866161, year = {2018}, author = {Agius, PA and Aitken, CK and Breen, C and Dietze, PM}, title = {Repeat participation in annual cross-sectional surveys of drug users and its implications for analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {349}, pmid = {29866161}, issn = {1756-0500}, mesh = {Australia/epidemiology ; Cities ; Cross-Sectional Studies ; *Drug Overdose ; Drug Users/*statistics & numerical data ; Humans ; Prevalence ; *Street Drugs ; Substance-Related Disorders/*epidemiology ; *Surveys and Questionnaires ; }, abstract = {OBJECTIVE: We sought to establish the extent of repeat participation in a large annual cross-sectional survey of people who inject drugs and assess its implications for analysis.

RESULTS: We used "porn star names" (the name of each participant's first pet followed by the name of the first street in which they lived) to identify repeat participation in three Australian Illicit Drug Reporting System surveys. Over 2013-2015, 2468 porn star names (96.2%) appeared only once, 88 (3.4%) twice, and nine (0.4%) in all 3 years. We measured design effects, based on the between-cluster variability for selected estimates, of 1.01-1.07 for seven key variables. These values indicate that the complex sample is (e.g.) 7% less efficient in estimating prevalence of heroin use (ever) than a simple random sample, and 1% less efficient in estimating number of heroin overdoses (ever). Porn star names are a useful means of tracking research participants longitudinally while maintaining their anonymity. Repeat participation in the Australian Illicit Drug Reporting System is low (less than 5% per annum), meaning point-prevalence and effect estimation without correction for the lack of independence in observations is unlikely to seriously affect population inference.}, } @article {pmid29866160, year = {2018}, author = {Shakoor, S and Ahmed, I and Mukhtiar, S and Ahmed, I and Hirani, F and Sultana, S and Hasan, R}, title = {High heterotrophic counts in potable water and antimicrobial resistance among indicator organisms in two peri-urban communities of Karachi, Pakistan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {350}, pmid = {29866160}, issn = {1756-0500}, support = {W/5710-1//International Foundation for Science/ ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/classification/*growth & development/metabolism ; Drinking Water/*microbiology ; *Drug Resistance, Bacterial ; Escherichia coli/drug effects/growth & development/metabolism ; Geography ; Heterotrophic Processes ; Humans ; Klebsiella pneumoniae/drug effects/growth & development/metabolism ; Pakistan ; Urban Population ; *Water Microbiology ; Water Supply/standards ; beta-Lactamases/metabolism ; }, abstract = {OBJECTIVE: Fecal contamination of potable water leads to unsafe water supply. Although many urban areas of large metropolitan cities receive safe water, peri-urban areas are often not monitored by public health authorities and water supply and quality remain unknown. We assessed microbiological quality and rates of antimicrobial resistance in viable indicator bacteria in two peri-urban communities of Karachi, Pakistan. Water samples were collected over 5 months (October 2015 to February 2016) from these peri-urban communities and samples were processed for microbiological quality as per Standing Committee of Analysts, United Kingdom and World Health Organization guidelines and criteria for drinking water.

RESULTS: Both communities received unimproved water. Potable water samples collected from 100 households showed that 96% of samples were unsafe for consumption. Extended spectrum beta lactamases production was found in 29.2% of fecal indicator organisms (coliforms). Use of unimproved water sources and unsafe potable water quality in peri-urban Karachi deserve immediate attention and upgrade. The study is instrumental in attracting the attention of authorities to the state of water resources in peri-urban communities in Karachi with a view to influence improvement of services and effects on human health.}, } @article {pmid29866078, year = {2018}, author = {Xiong, P and Hulsey, CD and Meyer, A and Franchini, P}, title = {Evolutionary divergence of 3' UTRs in cichlid fishes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {433}, pmid = {29866078}, issn = {1471-2164}, support = {NRF-CRP7-2010-02//National Research Foundation Singapore/ ; }, mesh = {3' Untranslated Regions/*genetics ; Animals ; Cichlids/*genetics ; *Evolution, Molecular ; MicroRNAs/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; }, abstract = {BACKGROUND: Post-transcriptional regulation is crucial for the control of eukaryotic gene expression and might contribute to adaptive divergence. The three prime untranslated regions (3' UTRs), that are located downstream of protein-coding sequences, play important roles in post-transcriptional regulation. These regions contain functional elements that influence the fate of mRNAs and could be exceptionally important in groups such as rapidly evolving cichlid fishes.

RESULTS: To examine cichlid 3' UTR evolution, we 1) identified gene features in nine teleost genomes and 2) performed comparative analyses to assess evolutionary variation in length, functional motifs, and evolutionary rates of 3' UTRs. In all nine teleost genomes, we found a smaller proportion of repetitive elements in 3' UTRs than in the whole genome. We found that the 3' UTRs in cichlids tend to be longer than those in non-cichlids, and this was associated, on average, with one more miRNA target per gene in cichlids. Moreover, we provided evidence that 3' UTRs on average have evolved faster in cichlids than in non-cichlids. Finally, analyses of gene function suggested that both the top 5% longest and 5% most rapidly evolving 3' UTRs in cichlids tended to be involved in ribosome-associated pathways and translation.

CONCLUSIONS: Our results reveal novel patterns of evolution in the 3' UTRs of teleosts in general and cichlids in particular. The data suggest that 3' UTRs might serve as important meta-regulators, regulators of other mechanisms governing post-transcriptional regulation, especially in groups like cichlids that have undergone extremely fast rates of phenotypic diversification and speciation.}, } @article {pmid29866053, year = {2018}, author = {Keel, BN and Zarek, CM and Keele, JW and Kuehn, LA and Snelling, WM and Oliver, WT and Freetly, HC and Lindholm-Perry, AK}, title = {RNA-Seq Meta-analysis identifies genes in skeletal muscle associated with gain and intake across a multi-season study of crossbred beef steers.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {430}, pmid = {29866053}, issn = {1471-2164}, mesh = {Animal Feed ; Animals ; Cattle/*genetics/growth & development ; Eating/*genetics ; *Hybridization, Genetic ; Male ; Muscle, Skeletal/*metabolism ; *Red Meat ; *Seasons ; *Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Feed intake and body weight gain are economically important inputs and outputs of beef production systems. The purpose of this study was to discover differentially expressed genes that will be robust for feed intake and gain across a large segment of the cattle industry. Transcriptomic studies often suffer from issues with reproducibility and cross-validation. One way to improve reproducibility is by integrating multiple datasets via meta-analysis. RNA sequencing (RNA-Seq) was performed on longissimus dorsi muscle from 80 steers (5 cohorts, each with 16 animals) selected from the outside fringe of a bivariate gain and feed intake distribution to understand the genes and pathways involved in feed efficiency. In each cohort, 16 steers were selected from one of four gain and feed intake phenotypes (n = 4 per phenotype) in a 2 × 2 factorial arrangement with gain and feed intake as main effect variables. Each cohort was analyzed as a single experiment using a generalized linear model and results from the 5 cohort analyses were combined in a meta-analysis to identify differentially expressed genes (DEG) across the cohorts.

RESULTS: A total of 51 genes were differentially expressed for the main effect of gain, 109 genes for the intake main effect, and 11 genes for the gain x intake interaction (Pcorrected < 0.05). A jackknife sensitivity analysis showed that, in general, the meta-analysis produced robust DEGs for the two main effects and their interaction. Pathways identified from over-represented genes included mitochondrial energy production and oxidative stress pathways for the main effect of gain due to DEG including GPD1, NDUFA6, UQCRQ, ACTC1, and MGST3. For intake, metabolic pathways including amino acid biosynthesis and degradation were identified, and for the interaction analysis the pathways identified included GADD45, pyridoxal 5'phosphate salvage, and caveolar mediated endocytosis signaling.

CONCLUSIONS: Variation among DEG identified by cohort suggests that environment and breed may play large roles in the expression of genes associated with feed efficiency in the muscle of beef cattle. Meta-analyses of transcriptome data from groups of animals over multiple cohorts may be necessary to elucidate the genetics contributing these types of biological phenotypes.}, } @article {pmid29866052, year = {2018}, author = {Wu, Z and Liu, Q and Li, Z and Cheng, W and Sun, J and Guo, Z and Li, Y and Zhou, J and Meng, D and Li, H and Lei, P and Yin, H}, title = {Environmental factors shaping the diversity of bacterial communities that promote rice production.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {51}, pmid = {29866052}, issn = {1471-2180}, abstract = {BACKGROUND: Exploiting soil microorganisms in the rhizosphere of plants can significantly improve agricultural productivity; however, the mechanism by which microorganisms specifically affect agricultural productivity is poorly understood. To clarify this uncertainly, the rhizospheric microbial communities of super rice plants at various growth stages were analysed using 16S rRNA high-throughput gene sequencing; microbial communities were then related to soil properties and rice productivity.

RESULTS: The rhizospheric bacterial communities were characterized by the phyla Proteobacteria, Acidobacteria, Chloroflexi, and Verrucomicrobia during all stages of rice growth. Rice production differed by approximately 30% between high- and low-yield sites that had uniform fertilization regimes and climatic conditions, suggesting the key role of microbial communities. Mantel tests showed a strong correlation between soil conditions and rhizospheric bacterial communities, and microorganisms had different effects on crop yield. Among the four growing periods, the rhizospheric bacterial communities present during the heading stage showed a more significant correlation (p < 0.05) with crop yield, suggesting their potential in regulating crop production. The biological properties (i.e., microbes) reflected the situation of agricultural land better than the physicochemical characterics (i.e., nutrient elements), which provides theoretical support for agronomic production. Molecular ecological network (MEN) analysis suggested that differences in productivity were caused by the interaction between the soil characteristics and the bacterial communities.

CONCLUSIONS: During the heading stage of rice cropping, the rhizospheric microbial community is vital for the resulting rice yield. According to network analysis, the cooperative relationship (i.e., positive interaction) between between microbes may contribute significantly to yield, and the biological properties (i.e., microbes) better reflected the real conditions of agricultural land than did the physicochemical characteristics (i.e., nutrient elements).}, } @article {pmid29866051, year = {2018}, author = {Garnica, M and Bacaicoa, E and Mora, V and San Francisco, S and Baigorri, R and Zamarreño, AM and Garcia-Mina, JM}, title = {Shoot iron status and auxin are involved in iron deficiency-induced phytosiderophores release in wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {105}, pmid = {29866051}, issn = {1471-2229}, mesh = {Azetidinecarboxylic Acid/*analogs & derivatives/metabolism ; Indoleacetic Acids/*metabolism ; Iron/deficiency/*metabolism ; Plant Growth Regulators/*metabolism ; Plant Leaves/genetics/physiology ; Plant Roots/genetics/physiology ; Plant Shoots/genetics/physiology ; Siderophores/*metabolism ; Signal Transduction ; Triticum/genetics/*physiology ; }, abstract = {BACKGROUND: The release of phytosiderephores (PS) to the rhizosphere is the main root response to iron (Fe) deficiency in graminaceous plants. We have investigated the role of the Fe status in the shoot as well as of the signaling pathways controlled by three relevant phytoregulators - indolacetic acid (IAA), ethylene and nitric oxide (NO) - in the regulation of this root response in Fe-starved wheat plants. To this end, the PS accumulation in the nutrient solution and the root expression of the genes encoding the nicotianamine aminotransferase (TaNAAT) and ferritin (TaFER) have been evaluated in plants subjected to different treatments.

RESULTS: The application of Fe to leaves of Fe-deficient plants prevented the increase in both PS root release and TaNAAT gene expression thus showing the relevant role of the shoot to root communication in the regulation of PS root release and some steps of PS biosynthesis. Experiments with specific hormone inhibitors showed that while ethylene and NO did not positively regulate Fe-deficiency induced PS root release, auxin plays an essential role in the regulation of this process. Moreover, the application of IAA to Fe-sufficient plants promoted both PS root release and TaNAAT gene expression thus indicating that auxin might be involved in the shoot to root signaling network regulating Fe-deficiency root responses in wheat.

CONCLUSIONS: These results therefore indicate that PS root release in Fe-deficient wheat plants is directly modulated by the shoot Fe status through signaling pathways involving, among other possible effectors, auxin.}, } @article {pmid29866048, year = {2018}, author = {O'Doherty, AM and McGettigan, P and Irwin, RE and Magee, DA and Gagne, D and Fournier, E and Al-Naib, A and Sirard, MA and Walsh, CP and Robert, C and Fair, T}, title = {Intragenic sequences in the trophectoderm harbour the greatest proportion of methylation errors in day 17 bovine conceptuses generated using assisted reproductive technologies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {438}, pmid = {29866048}, issn = {1471-2164}, support = {NETGP-340825-06//Natural Sciences and Engineering Research Council of Canada/ ; 07/SRC/B1156//Science Foundation Ireland/Ireland ; }, mesh = {Animals ; Cattle/*embryology/*genetics ; *DNA Methylation ; Genetic Loci/genetics ; *Reproductive Techniques, Assisted ; Trophoblasts/*metabolism ; }, abstract = {BACKGROUND: Assisted reproductive technologies (ART) are widely used to treat fertility issues in humans and for the production of embryos in mammalian livestock. The use of these techniques, however, is not without consequence as they are often associated with inauspicious pre- and postnatal outcomes including premature birth, intrauterine growth restriction and increased incidence of epigenetic disorders in human and large offspring syndrome in cattle. Here, global DNA methylation profiles in the trophectoderm and embryonic discs of in vitro produced (IVP), superovulation-derived (SOV) and unstimulated, synchronised control day 17 bovine conceptuses (herein referred to as AI) were interrogated using the EmbryoGENE DNA Methylation Array (EDMA). Pyrosequencing was used to validate four loci identified as differentially methylated on the array and to assess the differentially methylated regions (DMRs) of six imprinted genes in these conceptuses. The impact of embryo-production induced DNA methylation aberrations was determined using Ingenuity Pathway Analysis, shedding light on the potential functional consequences of these differences.

RESULTS: Of the total number of differentially methylated loci identified (3140) 77.3 and 22.7% were attributable to SOV and IVP, respectively. Differential methylation was most prominent at intragenic sequences within the trophectoderm of IVP and SOV-derived conceptuses, almost a third (30.8%) of the differentially methylated loci mapped to intragenic regions. Very few differentially methylated loci were detected in embryonic discs (ED); 0.16 and 4.9% of the differentially methylated loci were located in the ED of SOV-derived and IVP conceptuses, respectively. The overall effects of SOV and IVP on the direction of methylation changes were associated with increased methylation; 70.6% of the differentially methylated loci in SOV-derived conceptuses and 57.9% of the loci in IVP-derived conceptuses were more methylated compared to AI-conceptuses. Ontology analysis of probes associated with intragenic sequences suggests enrichment for terms associated with cancer, cell morphology and growth.

CONCLUSION: By examining (1) the effects of superovulation and (2) the effects of an in vitro system (oocyte maturation, fertilisation and embryo culture) we have identified that the assisted reproduction process of superovulation alone has the largest impact on the DNA methylome of subsequent embryos.}, } @article {pmid29866047, year = {2018}, author = {De Miccolis Angelini, RM and Abate, D and Rotolo, C and Gerin, D and Pollastro, S and Faretra, F}, title = {De novo assembly and comparative transcriptome analysis of Monilinia fructicola, Monilinia laxa and Monilinia fructigena, the causal agents of brown rot on stone fruits.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {436}, pmid = {29866047}, issn = {1471-2164}, mesh = {Ascomycota/*genetics/*physiology ; DNA, Bacterial/metabolism ; Fruit/*microbiology ; *Gene Expression Profiling ; Hydrolysis ; Membrane Transport Proteins/genetics/metabolism ; Molecular Sequence Annotation ; Oxidation-Reduction ; Plant Diseases/*microbiology ; }, abstract = {BACKGROUND: Brown rots are important fungal diseases of stone and pome fruits. They are caused by several Monilinia species but M. fructicola, M. laxa and M. fructigena are the most common all over the world. Although they have been intensively studied, the availability of genomic and transcriptomic data in public databases is still scant. We sequenced, assembled and annotated the transcriptomes of the three pathogens using mRNA from germinating conidia and actively growing mycelia of two isolates of opposite mating types per each species for comparative transcriptome analyses.

RESULTS: Illumina sequencing was used to generate about 70 million of paired-end reads per species, that were de novo assembled in 33,861 contigs for M. fructicola, 31,103 for M. laxa and 28,890 for M. fructigena. Approximately, 50% of the assembled contigs had significant hits when blasted against the NCBI non-redundant protein database and top-hits results were represented by Botrytis cinerea, Sclerotinia sclerotiorum and Sclerotinia borealis proteins. More than 90% of the obtained sequences were complete, the percentage of duplications was always less than 14% and fragmented and missing transcripts less than 5%. Orthologous transcripts were identified by tBLASTn analysis using the B. cinerea proteome as reference. Comparative transcriptome analyses revealed 65 transcripts over-expressed (FC ≥ 8 and FDR ≤ 0.05) or unique in M. fructicola, 30 in M. laxa and 31 in M. fructigena. Transcripts were involved in processes affecting fungal development, diversity and host-pathogen interactions, such as plant cell wall-degrading and detoxifying enzymes, zinc finger transcription factors, MFS transporters, cell surface proteins, key enzymes in biosynthesis and metabolism of antibiotics and toxins, and transposable elements.

CONCLUSIONS: This is the first large-scale reconstruction and annotation of the complete transcriptomes of M. fructicola, M. laxa and M. fructigena and the first comparative transcriptome analysis among the three pathogens revealing differentially expressed genes with potential important roles in metabolic and physiological processes related to fungal morphogenesis and development, diversity and pathogenesis which need further investigations. We believe that the data obtained represent a cornerstone for research aimed at improving knowledge on the population biology, physiology and plant-pathogen interactions of these important phytopathogenic fungi.}, } @article {pmid29866046, year = {2018}, author = {Miao, B and Xiao, Q and Chen, W and Li, Y and Wang, Z}, title = {Evaluation of functionality for serine and threonine phosphorylation with different evolutionary ages in human and mouse.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {431}, pmid = {29866046}, issn = {1471-2164}, support = {2017YFA0505500, 2016YFC0901704//National Key R&D Program of China/ ; 2017325//Youth Innovation Promotion Association of the Chinese Academy of Sciences/ ; 31301032//National Natural Science Foundation of China/ ; 13R21417300//Shanghai Postdoctoral Scientific Program/ ; }, mesh = {Animals ; *Evolution, Molecular ; Humans ; Mice ; Phosphorylation ; Serine/*metabolism ; Threonine/*metabolism ; }, abstract = {BACKGROUND: Rapid evolution of phosphorylation sites could provide raw materials of natural selection to fit the environment by rewiring the regulation of signal pathways. However, a large part of phosphorylation sites was suggested to be non-functional. Although the new-arising phosphorylation sites with little functional implications prevailed in fungi, the evolutionary performance of vertebrate phosphorylation sites remained elusive.

RESULTS: In this study, we evaluated the functionality of human and mouse phosphorylation sites by dividing them into old, median and young age groups based on the phylogeny of vertebrates. We found the sites in the old group were more likely to be functional and involved in signaling pathways than those in the young group. A smaller proportion of sites in the young group originated from aspartate/glutamate, which could restore the ancestral functions. In addition, both the phosphorylation level and breadth was increased with the evolutionary age. Similar to cases in fungi, these results implied that the newly emerged phosphorylation sites in vertebrates were also more likely to be non-functional, especially for serine and threonine phosphorylation in disordered regions.

CONCLUSIONS: This study provided not only insights into the dynamics of phosphorylation evolution in vertebrates, but also new clues to identify the functional phosphorylation sites from massive noisy data.}, } @article {pmid29866045, year = {2018}, author = {Zhang, S and Li, M and Ji, H and Fang, Z}, title = {Landscape of transcriptional deregulation in lung cancer.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {435}, pmid = {29866045}, issn = {1471-2164}, support = {81430066, 91731314, 31621003//National Natural Science Foundation of China/ ; 81602459//National Natural Science Foundation of China/ ; 2017YFA0505500//National Basic Research Program of China/ ; XDB19000000//Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, mesh = {*Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Lung Neoplasms/*genetics ; SOXB1 Transcription Factors/metabolism ; Transcription Factors/metabolism ; *Transcription, Genetic ; Tumor Suppressor Proteins/metabolism ; }, abstract = {BACKGROUND: Lung cancer is a very heterogeneous disease that can be pathologically classified into different subtypes including small-cell lung carcinoma (SCLC), lung adenocarcinoma (LUAD), lung squamous cell carcinoma (LUSC) and large-cell carcinoma (LCC). Although much progress has been made towards the oncogenic mechanism of each subtype, transcriptional circuits mediating the upstream signaling pathways and downstream functional consequences remain to be systematically studied.

RESULTS: Here we trained a one-class support vector machine (OC-SVM) model to establish a general transcription factor (TF) regulatory network containing 325 TFs and 18724 target genes. We then applied this network to lung cancer subtypes and identified those deregulated TFs and downstream targets. We found that the TP63/SOX2/DMRT3 module was specific to LUSC, corresponding to squamous epithelial differentiation and/or survival. Moreover, the LEF1/MSC module was specifically activated in LUAD and likely to confer epithelial-to-mesenchymal transition, known important for cancer malignant progression and metastasis. The proneural factor, ASCL1, was specifically up-regulated in SCLC which is known to have a neuroendocrine phenotype. Also, ID2 was differentially regulated between SCLC and LUSC, with its up-regulation in SCLC linking to energy supply for fast mitosis and its down-regulation in LUSC linking to the attenuation of immune response. We further described the landscape of TF regulation among the three major subtypes of lung cancer, highlighting their functional commonalities and specificities.

CONCLUSIONS: Our approach uncovered the landscape of transcriptional deregulation in lung cancer, and provided a useful resource of TF regulatory network for future studies.}, } @article {pmid29866044, year = {2018}, author = {Zoupa, M and Xavier, GM and Bryan, S and Theologidis, I and Arno, M and Cobourne, MT}, title = {Gene expression profiling in the developing secondary palate in the absence of Tbx1 function.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {429}, pmid = {29866044}, issn = {1471-2164}, mesh = {Animals ; Female ; *Gene Deletion ; *Gene Expression Profiling ; Genotype ; Mice ; Palate/*growth & development ; T-Box Domain Proteins/*deficiency/*genetics ; }, abstract = {BACKGROUND: Microdeletion of chromosome 22q11 is associated with significant developmental anomalies, including disruption of the cardiac outflow tract, thymic/parathyroid aplasia and cleft palate. Amongst the genes within this region, TBX1 is a major candidate for many of these developmental defects. Targeted deletion of Tbx1 in the mouse has provided significant insight into the function of this transcription factor during early development of the cardiac and pharyngeal systems. However, less is known about its role during palatogenesis. To assess the influence of Tbx1 function on gene expression profile within the developing palate we performed a microarray screen using total RNA isolated from the secondary palate of E13.5 mouse embryos wild type, heterozygous and mutant for Tbx1.

RESULTS: Expression-level filtering and statistical analysis revealed a total of 577 genes differentially expressed across genotypes. Data were clustered into 3 groups based on comparison between genotypes. Group A was composed of differentially expressed genes in mutant compared to wild type (n = 89); Group B included differentially expressed genes in heterozygous compared to wild type (n = 400) and Group C included differentially expressed genes in mutant compared to heterozygous (n = 88). High-throughput quantitative real-time PCR (RT-PCR) confirmed a total of 27 genes significantly changed between wild type and mutant; and 27 genes between heterozygote and mutant. Amongst these, the majority were present in both groups A and C (26 genes). Associations existed with hypertrophic cardiomyopathy, cardiac muscle contraction, dilated cardiomyopathy, focal adhesion, tight junction and calcium signalling pathways. No significant differences in gene expression were found between wild type and heterozygous palatal shelves.

CONCLUSIONS: Significant differences in gene expression profile within the secondary palate of wild type and mutant embryos is consistent with a primary role for Tbx1 during palatogenesis.}, } @article {pmid29866043, year = {2018}, author = {Gagunashvili, AN and Andrésson, ÓS}, title = {Distinctive characters of Nostoc genomes in cyanolichens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {434}, pmid = {29866043}, issn = {1471-2164}, support = {130455-051//Icelandic Centre for Research/ ; }, mesh = {Genome, Bacterial/genetics ; *Genomics ; Lichens/*microbiology ; Molecular Sequence Annotation ; Nostoc/*genetics/metabolism/physiology ; Organophosphonates/metabolism ; Sequence Analysis, DNA ; Symbiosis ; }, abstract = {BACKGROUND: Cyanobacteria of the genus Nostoc are capable of forming symbioses with a wide range of organism, including a diverse assemblage of cyanolichens. Only certain lineages of Nostoc appear to be able to form a close, stable symbiosis, raising the question whether symbiotic competence is determined by specific sets of genes and functionalities.

RESULTS: We present the complete genome sequencing, annotation and analysis of two lichen Nostoc strains. Comparison with other Nostoc genomes allowed identification of genes potentially involved in symbioses with a broad range of partners including lichen mycobionts. The presence of additional genes necessary for symbiotic competence is likely reflected in larger genome sizes of symbiotic Nostoc strains. Some of the identified genes are presumably involved in the initial recognition and establishment of the symbiotic association, while others may confer advantage to cyanobionts during cohabitation with a mycobiont in the lichen symbiosis.

CONCLUSIONS: Our study presents the first genome sequencing and genome-scale analysis of lichen-associated Nostoc strains. These data provide insight into the molecular nature of the cyanolichen symbiosis and pinpoint candidate genes for further studies aimed at deciphering the genetic mechanisms behind the symbiotic competence of Nostoc. Since many phylogenetic studies have shown that Nostoc is a polyphyletic group that includes several lineages, this work also provides an improved molecular basis for demarcation of a Nostoc clade with symbiotic competence.}, } @article {pmid29866042, year = {2018}, author = {Tervaniemi, MH and Katayama, S and Skoog, T and Siitonen, HA and Vuola, J and Nuutila, K and Tammimies, K and Suomela, S and Kankuri, E and Kere, J and Elomaa, O}, title = {Intracellular signalling pathways and cytoskeletal functions converge on the psoriasis candidate gene CCHCR1 expressed at P-bodies and centrosomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {432}, pmid = {29866042}, issn = {1471-2164}, support = {130360, 1255560//Academy of Finland/ ; }, mesh = {Cell Adhesion ; Centrosome/*metabolism ; Cytoskeleton/*metabolism ; *Gene Expression Regulation ; HEK293 Cells ; Haplotypes ; Humans ; Intracellular Signaling Peptides and Proteins/*genetics ; Intracellular Space/*metabolism ; Psoriasis/*genetics/pathology ; *Signal Transduction ; Skin/metabolism/pathology ; }, abstract = {BACKGROUND: CCHCR1 (Coiled-Coil α-Helical Rod protein 1) is a putative psoriasis candidate gene with the risk alleles CCHCR1*WWCC and *Iso3, the latter inhibiting the translation of isoform 1. CCHCR1 was recently shown to be a centrosomal protein, as well as a component of cytoplasmic processing bodies (P-bodies) that regulate mRNA turnover. The function of CCHCR1 has remained unsettled, partly because of the inconsistent findings; it has been shown to play a wide variety of roles in divergent processes, e.g., cell proliferation and steroidogenesis. Here we utilized RNA sequencing (RNAseq) using HEK293 cells overexpressing isoforms 1 or 3 (Iso1, Iso3 cells), in combination with the coding non-risk or risk (*WWCC) haplotype of CCHCR1. Our aim was to study the overall role of CCHCR1 and the effects of its variants.

RESULTS: The overexpression of CCHCR1 variants in HEK293 cells resulted in cell line-specific expression profiles though several similarities were observable. Overall the Iso1 and Iso3 cells showed a clear isoform-specific clustering as two separate groups, and the Non-risk and Risk cells often exhibited opposite effects. The RNAseq supported a role for CCHCR1 in the centrosomes and P-bodies; the most highlighted pathways included regulation of cytoskeleton, adherens and tight junctions, mRNA surveillance and RNA transport. Interestingly, both the RNAseq and immunofluorescent localization revealed variant-specific differences for CCHCR1 within the P-bodies.

CONCLUSIONS: CCHCR1 influenced a wide variety of signaling pathways, which could reflect its active role in the P-bodies and centrosomes that both are linked to the cytoskeleton; as a centrosomal P-body protein CCHCR1 may regulate diverse cytoskeleton-mediated functions, such as cell adhesion and -division. The present findings may explain the previous inconsistent observations about the functions of CCHCR1.}, } @article {pmid29866041, year = {2018}, author = {Zhu, YJ and Li, XY and Zhang, J and Li, Z and Ding, M and Zhang, XJ and Zhou, L and Gui, JF}, title = {Distinct sperm nucleus behaviors between genotypic and temperature-dependent sex determination males are associated with replication and expression-related pathways in a gynogenetic fish.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {437}, pmid = {29866041}, issn = {1471-2164}, support = {QYZDY-SSW-SMC025//Chinese Academy of Sciences/ ; XDA08030201//Chinese Academy of Sciences/ ; 31502148//National Natural Science Foundation of China/ ; YESS20150156//China Association for Science and Technology (CN)/ ; NYCYTX-49//Ministry of Agriculture of the People's Republic of China/ ; 2016FBZ01//State Key Laboratory of Freshwater Ecology and Biotechnology/ ; Y25A171//Institute of Hydrobiology Chinese Academy of Sciences/ ; }, mesh = {Animals ; Cell Nucleus/metabolism ; *DNA Replication ; Female ; Fish Proteins/genetics ; Fishes/*genetics/physiology ; *Genotype ; Male ; Reproduction, Asexual/*genetics ; *Sex Determination Processes ; Spermatozoa/*cytology ; *Temperature ; }, abstract = {BACKGROUND: Coexistence and transition of diverse sex determination strategies have been revealed in some ectothermic species, but the variation between males caused by different sex determination strategies and the underlying mechanism remain unclear. Here, we used the gynogenetic gibel carp (Carassius gibelio) with both genotypic sex determination (GSD) and temperature-dependent sex determination (TSD) strategies to illustrate this issue.

RESULTS: We found out that males of GSD and TSD in gibel carp had similar morphology, testicular histology, sperm structure and sperm vitality. However, when maternal individuals were mated with males of GSD, sperm nucleus swelling and fusing with the female pronucleus were observed in the fertilized eggs. On the contrary, when maternal individuals were mated with males of TSD, sperm nucleus remained in the condensed status throughout the whole process. Subsequently, semen proteomics analysis unveiled that DNA replication and gene expression-related pathways were inhibited in the sperm from males of TSD compared to males of GSD, and most differentially expressed proteins associated with DNA replication, transcription and translation were down-regulated. Moreover, via BrdU incorporation and immunofluorescence detection, male nucleus replication was revealed to be present in the fertilized eggs by the sperm from males of GSD, but absent in the fertilized eggs by the sperm from males of TSD.

CONCLUSIONS: These findings indicate that DNA replication and gene expression-related pathways are associated with the distinct sperm nucleus development behaviors in fertilized eggs in response to the sperm from males of GSD and TSD. And this study is the first attempt to screen the differences between males determined via GSD and TSD in gynogenetic species, which might give a hint for understanding evolutionary adaption of diverse sex determination mechanisms in unisexual vertebrates.}, } @article {pmid29866040, year = {2018}, author = {Lyu, G and Zhang, C and Ling, T and Liu, R and Zong, L and Guan, Y and Huang, X and Sun, L and Zhang, L and Li, C and Nie, Y and Tao, W}, title = {Genome and epigenome analysis of monozygotic twins discordant for congenital heart disease.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {428}, pmid = {29866040}, issn = {1471-2164}, support = {No. 2014M550007//China Postdoctoral Science Foundation 55th General Financial Grant/ ; No.31471205//Postdoctoral Fellowship of Peking University-Tshinghua University Center for Life Sciences/ ; 2013CB530700//National Basic Research Program of China (973 Program)/ ; }, mesh = {COUP Transcription Factor II/genetics ; Child, Preschool ; DNA Methylation ; Double Outlet Right Ventricle/*genetics ; Epigenesis, Genetic ; *Epigenomics ; Female ; Gene Ontology ; Homeodomain Proteins/genetics ; Humans ; Infant ; Male ; Promoter Regions, Genetic/genetics ; Transcription Factors/genetics ; Twins, Monozygotic/*genetics ; }, abstract = {BACKGROUND: Congenital heart disease (CHD) is the leading non-infectious cause of death in infants. Monozygotic (MZ) twins share nearly all of their genetic variants before and after birth. Nevertheless, MZ twins are sometimes discordant for common complex diseases. The goal of this study is to identify genomic and epigenomic differences between a pair of twins discordant for a form of congenital heart disease, double outlet right ventricle (DORV).

RESULTS: A monoamniotic monozygotic (MZ) twin pair discordant for DORV were subjected to genome-wide sequencing and methylation analysis. We identified few genomic differences but 1566 differentially methylated regions (DMRs) between the MZ twins. Twenty percent (312/1566) of the DMRs are located within 2 kb upstream of transcription start sites (TSS), containing 121 binding sites of transcription factors. Particularly, ZIC3 and NR2F2 are found to have hypermethylated promoters in both the diseased twin and additional patients suffering from DORV.

CONCLUSIONS: The results showed a high correlation between hypermethylated promoters at ZIC3 and NR2F2 and down-regulated gene expression levels of these two genes in patients with DORV compared to normal controls, providing new insight into the potential mechanism of this rare form of CHD.}, } @article {pmid29866039, year = {2018}, author = {Kochevenko, A and Jiang, Y and Seiler, C and Surdonja, K and Kollers, S and Reif, JC and Korzun, V and Graner, A}, title = {Identification of QTL hot spots for malting quality in two elite breeding lines with distinct tolerance to abiotic stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {106}, pmid = {29866039}, issn = {1471-2229}, mesh = {Chromosome Mapping ; Droughts ; Genotype ; Haploidy ; Hordeum/*genetics/physiology ; Phenotype ; Plant Breeding ; Quantitative Trait Loci/*genetics ; Seeds/genetics/physiology ; *Stress, Physiological ; }, abstract = {BACKGROUND: Barley (Hordeum vulgare) is an important crop cultivated across the world. Drought is a major abiotic factor compromising barley yield worldwide, therefore in modern spring barley cultivars superior seed and malting quality characteristics should be combined with reasonable level of drought tolerance. Previously we have identified a number of barley lines demonstrating the superior yield performance under drought conditions. The aim of this work was to perform a QTL analysis of malting quality traits in a doubled haploid (DH) mapping population of two elite barley lines that differ in their reaction pattern to drought stress.

RESULTS: A population of DH lines was developed by crossing two drought-tolerant elite breeding lines, Victoriana and Sofiara, exploiting distinct mechanism of drought tolerance, sustaining assimilation vs remobilization. The mapping population was assayed under field conditions at four distinct locations that differed in precipitation rate. DH lines were genotyped with the Illumina 9 K iSelect assay, and linkage map including 1782 polymorphic markers and covering a total map length of 1140 cM was constructed. The result of quantitative trait loci (QTL) analysis showed that majority of the traits were affected by several main effect QTL and/or QTL x environment (QE) interactions. In total, 57, 41, and 5 QTL were associated with yield-related traits, malting quality traits and seed quality traits, respectively. 11 and 29 of mapped QTL explained more than 10 and 5% of phenotypic variation, respectively. In several chromosomal regions co-localization between QTL for various traits were observed. The largest clusters were detected on chromosomes 3H and 4H.

CONCLUSIONS: Our QTL mapping results revealed several novel consistent genomic regions controlling malting quality which could be exploited in marker assisted selection. In this context, the complex QTL region on chromosome 3H seems of particular interest, as it harbors several large effect QTL.}, } @article {pmid29866038, year = {2018}, author = {Zhang, Y and Li, Z and Tu, Y and Cheng, W and Yang, Y}, title = {Tomato (Solanum lycopersicum) SlIPT4, encoding an isopentenyltransferase, is involved in leaf senescence and lycopene biosynthesis during fruit ripening.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {107}, pmid = {29866038}, issn = {1471-2229}, support = {31372080//National Natural Science Foundation of China/ ; cstc2017jcyjAX0455//Committee of Science and Technology of Chongqing, China/ ; 106112013CDJZR290035//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Abscisic Acid/metabolism ; Alkyl and Aryl Transferases/genetics/*metabolism ; Cytokinins/metabolism ; Fruit/enzymology/genetics/physiology ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Plant ; Gene Regulatory Networks ; Lycopene/*metabolism ; Lycopersicon esculentum/*enzymology/genetics/physiology ; Plant Growth Regulators/*metabolism ; Plant Leaves/enzymology/genetics/physiology ; Plant Proteins/genetics/metabolism ; RNA Interference ; }, abstract = {BACKGROUND: Lycopene is an important carotenoid pigment in red fruits and vegetables, especially in tomato. Although lycopene biosynthesis and catabolism have been found to be regulated by multiple factors including phytohormones, little is known about their regulatory mechanism. Cytokinins are crucial to various aspects of plant growth. Isopentenyltransferases (IPTs) catalyze the initial rate-limiting step of cytokinins biosynthesis, however, their roles in fruit ripening remain unclear.

RESULTS: Here, the functions of SlIPT4, encoding an isopentenyltransferase, were characterized via RNAi-mediated gene silencing in tomato. As we expected, silencing of SlIPT4 expression resulted in accelerated leaf senescence. However, down-expression of SlIPT4 generated never-red orange fruits, corresponding with a dramatic reduction of lycopene. Among lycopene biosynthesis-related genes, the fact of remarkable decrease of ZISO transcript and upregulation of other genes, revealed that SlIPT4 regulates positively lycopene biosynthesis via directly affecting ZISO expression, and also supported the existence of regulatory loops in lycopene biosynthesis pathway. Meanwhile, the accumulation of abscisic acid (ABA) was reduced and the transcripts PSY1 were increased in SlIPT4-RNAi fruits, supporting the feedback regulation between ABA and lycopene biosynthesis.

CONCLUSION: The study revealed the crucial roles of SlIPT4 in leaf senescence and the regulatory network of lycopene biosynthesis in tomato, providing a new light on the lycopene biosynthesis and fruit ripening.}, } @article {pmid29866037, year = {2018}, author = {Janssens, Y and Nielandt, J and Bronselaer, A and Debunne, N and Verbeke, F and Wynendaele, E and Van Immerseel, F and Vandewynckel, YP and De Tré, G and De Spiegeleer, B}, title = {Disbiome database: linking the microbiome to disease.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {50}, pmid = {29866037}, issn = {1471-2180}, abstract = {BACKGROUND: Recent research has provided fascinating indications and evidence that the host health is linked to its microbial inhabitants. Due to the development of high-throughput sequencing technologies, more and more data covering microbial composition changes in different disease types are emerging. However, this information is dispersed over a wide variety of medical and biomedical disciplines.

DESCRIPTION: Disbiome is a database which collects and presents published microbiota-disease information in a standardized way. The diseases are classified using the MedDRA classification system and the micro-organisms are linked to their NCBI and SILVA taxonomy. Finally, each study included in the Disbiome database is assessed for its reporting quality using a standardized questionnaire.

CONCLUSIONS: Disbiome is the first database giving a clear, concise and up-to-date overview of microbial composition differences in diseases, together with the relevant information of the studies published. The strength of this database lies within the combination of the presence of references to other databases, which enables both specific and diverse search strategies within the Disbiome database, and the human annotation which ensures a simple and structured presentation of the available data.}, } @article {pmid29866036, year = {2018}, author = {Yang, C and Liang, Y and Qiu, D and Zeng, H and Yuan, J and Yang, X}, title = {Lignin metabolism involves Botrytis cinerea BcGs1- induced defense response in tomato.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {103}, pmid = {29866036}, issn = {1471-2229}, support = {2017YFD0201100//National Key Research and Development Program of China/ ; }, mesh = {Botrytis/*enzymology/physiology ; Cell Wall/metabolism ; *Disease Resistance ; Fungal Proteins/metabolism ; Glucan 1,4-alpha-Glucosidase/*metabolism ; Host-Pathogen Interactions ; Hydrogen Peroxide/metabolism ; Lignin/*metabolism ; Lycopersicon esculentum/*immunology/metabolism/microbiology ; Peroxidase/metabolism ; Phenylalanine Ammonia-Lyase/metabolism ; Plant Diseases/*immunology/microbiology ; Plant Proteins/metabolism ; Propanols/metabolism ; Protein Domains ; Reactive Oxygen Species/metabolism ; Secondary Metabolism ; }, abstract = {BACKGROUND: BcGs1, a cell wall-degrading enzyme (CWDE), was originally derived from Botrytis cinerea. Our previous study revealed that BcGs1 could trigger defense responses and protect plants against various pathogens. We researched the defense response mechanism underlying this BcGs1 elicitation in tomato.

RESULTS: We revealed that the two domains were required for BcGs1's full necrosis activity. According to analysis and quantitative real-time PCR of the up-regulated proteins and genes filtered by iTRAQ-based quantitative proteome approach, oxidative metabolism and phenylpropanoid metabolism were speculated to be involved in BcGs1-triggered defense response in tomato. Furthermore, experimental evidence showed that BcGs1 triggered reactive oxygen species (ROS) burst and increased the level of phenylalanine-ammonia lyase (PAL) and peroxidase (POD) enzyme activity, as well as lignin accumulation. Moreover, histochemical analysis revealed that infiltration of BcGs1 in tomato leaves exhibited cell wall thickening compared with untreated plants.

CONCLUSIONS: The results suggested that BcGs1 activated the basal defense response included lignin metabolism contributed to BcGs1-induced resistance to Botrytis. cinerea infection in tomato.}, } @article {pmid29866035, year = {2018}, author = {Zhou, B and Ma, C and Wang, H and Xia, T}, title = {Biodegradation of caffeine by whole cells of tea-derived fungi Aspergillus sydowii, Aspergillus niger and optimization for caffeine degradation.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {53}, pmid = {29866035}, issn = {1471-2180}, abstract = {BACKGROUND: Pu-erh tea is a traditional Chinese tea and produced by natural solid-state fermentation. Several studies show that the natural microbiota influence caffeine level in pu-erh tea. Our previous research also found that the caffeine declined significantly (p < 0.05) in the fermentation, which suggested that the caffeine level could be influenced by specific strains. The purpose of this study was to isolate and identify microorganisms for caffeine degradation, and this research explored the degradation products from caffeine and optimal condition for caffeine degradation.

RESULTS: 11 Fungi were isolated from pu-erh tea fermentation and 7 strains could survive in caffeine solid medium. Two superior strains were identified as Aspergillus niger NCBT110A and Aspergillus sydowii NRRL250 by molecular identification. In the substrate tests with caffeine, A. niger NCBT110A could use caffeine as a potential carbon source while glucose is absent, A. sydowii NRRL250 could degrade 600 mg/L caffeine completely in a liquid medium. During the degradation product analysis of A. sydowii NRRL250, theophylline and 3-methlxanthine were detected, and the level of theophylline and 3-methlxanthine increased significantly (p < 0.05) with the degradation of caffeine. The single factor analysis showed that the optimum conditions of caffeine degradation were 1) substrate concentration of 1200 mg/L, 2) reaction temperature at 30 °C, and 3) pH of 6. In the submerged fermentation of tea infusion by A. sydowii NRRL250, 985.1 mg/L of caffeine was degraded, and 501.2 mg/L of theophylline was produced.

CONCLUSIONS: Results from this research indicate that Aspergillus sydowii NRRL250 was an effective strain to degrade caffeine. And theophylline and 3-methlxanthine were the main caffeine degradation products.}, } @article {pmid29866033, year = {2018}, author = {Jiang, L and Pan, H}, title = {Functions of CaPhm7 in the regulation of ion homeostasis, drug tolerance, filamentation and virulence in Candida albicans.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {49}, pmid = {29866033}, issn = {1471-2180}, abstract = {BACKGROUND: Calcium-permeable transient receptor potential (TRP) channels exist in eukaryotic cells from yeasts to animals and plants. and they act as sensors for various stresses. Arabidopsis thaliana calcium permeable stress-gated cation channel 1 (AtCSC1) was the first plant calcium-permeable TRP to be described and can be activated by hyperosmotic shock. Candida albicans CaPHM7 is one of the sequence homologs of AtCSC1, but its function remains unknown.

RESULTS: We show here that CaPhm7 is localized to the plasma membrane in both the yeast and hyphal cells of C. albicans. C. albicans cells lacking CaPHM7 are sensitive to SDS and ketoconazole but tolerant to rapamycin and zinc. In addition, deletion of CaPHM7 leads to a filamentation defect, reduced colony growth and attenuated virulence in the mouse model of systemic infection.

CONCLUSIONS: CaPhm7 is involved in the regulation of ion homeostasis, drug tolerance, filamentation and virulence in this important human fungal pathogen. CaPhm7 could be a potential target of antifungal drugs.}, } @article {pmid29866032, year = {2018}, author = {Wang, J and Yang, Y and Jin, L and Ling, X and Liu, T and Chen, T and Ji, Y and Yu, W and Zhang, B}, title = {Re-analysis of long non-coding RNAs and prediction of circRNAs reveal their novel roles in susceptible tomato following TYLCV infection.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {104}, pmid = {29866032}, issn = {1471-2229}, support = {BK20150543//Natural Science Foundation of Jiangsu Province/ ; 31471873//National Natural Science Foundation of China/ ; 31671980//National Natural Science Foundation of China/ ; 31401694//National Natural Science Foundation of China/ ; 31672096//National Natural Science Foundation of China/ ; 31701918//National Natural Science Foundation of China (CN)/ ; }, mesh = {Begomovirus/*physiology ; Disease Susceptibility ; Gene Silencing ; Lycopersicon esculentum/*genetics/immunology/virology ; Phenotype ; Plant Diseases/*immunology/virology ; Plant Leaves/genetics/immunology/virology ; RNA/*genetics ; RNA, Long Noncoding/*genetics ; RNA, Plant/genetics ; }, abstract = {BACKGROUND: Long Noncoding-RNAs (LncRNAs) are known to be involved in some biological processes, but their roles in plant-virus interactions remain largely unexplored. While circular RNAs (circRNAs) have been studied in animals, there has yet to be extensive research on them in a plant system, especially in tomato-tomato yellow leaf curl virus (TYLCV) interaction.

RESULTS: In this study, RNA transcripts from the susceptible tomato line JS-CT-9210 either infected with TYLCV or untreated, were sequenced in a pair-end strand-specific manner using ribo-zero rRNA removal library method. A total of 2056 lncRNAs including 1767 long intergenic non-coding RNA (lincRNAs) and 289 long non-coding natural antisense transcripts (lncNATs) were obtained. The expression patterns in lncRNAs were similar in susceptible tomato plants between control check (CK) and TYLCV infected samples. Our analysis suggested that lncRNAs likely played a role in a variety of functions, including plant hormone signaling, protein processing in the endoplasmic reticulum, RNA transport, ribosome function, photosynthesis, glulathione metabolism, and plant-pathogen interactions. Using virus-induced gene silencing (VIGS) analysis, we found that reduced expression of the lncRNA S-slylnc0957 resulted in enhanced resistance to TYLCV in susceptible tomato plants. Moreover, we identified 184 circRNAs candidates using the CircRNA Identifier (CIRI) software, of which 32 circRNAs were specifically expressed in untreated samples and 83 circRNAs in TYLCV samples. Approximately 62% of these circRNAs were derived from exons. We validated the circRNAs by both PCR and Sanger sequencing using divergent primers, and found that most of circRNAs were derived from the exons of protein coding genes. The silencing of these circRNAs parent genes resulted in decreased TYLCV virus accumulation.

CONCLUSION: In this study, we identified novel lncRNAs and circRNAs using bioinformatic approaches and showed that these RNAs function as negative regulators of TYLCV infection. Moreover, the expression patterns of lncRNAs in susceptible tomato plants were different from that of resistant tomato plants, while exonic circRNAs expression positively associated with their respective protein coding genes. This work provides a foundation for elaborating the novel roles of lncRNAs and circRNAs in susceptible tomatoes following TYLCV infection.}, } @article {pmid29866031, year = {2018}, author = {Burdach, Z and Siemieniuk, A and Trela, Z and Kurtyka, R and Karcz, W}, title = {Role of auxin (IAA) in the regulation of slow vacuolar (SV) channels and the volume of red beet taproot vacuoles.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {102}, pmid = {29866031}, issn = {1471-2229}, mesh = {Beta vulgaris/*physiology ; Cytoplasm/metabolism ; Electrophysiological Phenomena ; Indoleacetic Acids/*metabolism ; Intracellular Membranes/metabolism ; Ion Channels/physiology ; Organelle Size ; Patch-Clamp Techniques ; Plant Growth Regulators/*metabolism ; Plant Roots/physiology ; Vacuoles/metabolism ; }, abstract = {BACKGROUND: Auxin (IAA) is a central player in plant cell growth. In contrast to the well-established function of the plasma membrane in plant cell expansion, little is known about the role of the vacuolar membrane (tonoplast) in this process.

RESULTS: It was found that under symmetrical 100 mM K+ and 100 μM cytoplasmic Ca2+ the macroscopic currents showed a typical slow activation and a strong outward rectification of the steady-state currents. The addition of IAA at a final concentration of 1 μM to the bath medium stimulated the SV currents, whereas at 0.1 and 10 μM slight inhibition of SV currents was observed. The time constant, τ, decreased in the presence of this hormone. When single channels were analyzed, an increase in their activity was recorded with IAA compared to the control. The single-channel recordings that were obtained in the presence of IAA showed that auxin increased the amplitude of the single-channel currents. Interestingly, the addition of IAA to the bath medium with the same composition as the one that was used in the patch-clamp experiments showed that auxin decreased the volume of the vacuoles.

CONCLUSIONS: It is suggested that the SV channels and the volume of red beet taproot vacuoles are modulated by auxin (IAA).}, } @article {pmid29866030, year = {2018}, author = {Teng, T and Xi, B and Chen, K and Pan, L and Xie, J and Xu, P}, title = {Comparative transcriptomic and proteomic analyses reveal upregulated expression of virulence and iron transport factors of Aeromonas hydrophila under iron limitation.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {52}, pmid = {29866030}, issn = {1471-2180}, abstract = {BACKGROUND: Iron plays important roles in the growth, reproduction and pathogenicity of Aeromonas hydrophila. In this study, we detected and compared the mRNA and protein expression profiles of A. hydrophila under normal and iron restricted medium with 200 μM 2,2-Dipyridyl using RNA Sequencing (RNA-seq) and isobaric tags for relative and absolute quantification (iTRAQ) analyses.

RESULTS: There were 1204 genes (601 up- and 603 down-regulated) and 236 proteins (90 up- and 146 down-regulated) shown to be differentially expressed, and 167 genes and proteins that showed consistent expression. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses revealed that the differentially expressed genes and proteins were mainly involved in iron ion transport, protein activity, energy metabolism and virulence processes. Further validation of the RNA-seq and iTRAQ results by quantitative real-time PCR (qPCR) revealed that 18 of the 20 selected genes were consistently expressed. The iron-ion absorption and concentration of A. hydrophila under iron-limited conditions were enhanced, and most virulence factors (protease activity, hemolytic activity, lipase activity, and swimming ability) were also increased. Artificial A. hydrophila infection caused higher mortality in cyprinid Megalobrama amblycephala under iron-limited conditions.

CONCLUSION: Understanding the responses of pathogenic Aeromonas hydrophila within the hostile environment of the fish host, devoid of free iron, is important to reveal bacterial infection and pathogenesis. This study further confirmed the previous finding that iron-limitation efficiently enhanced the virulence of A. hydrophila using multi-omics analyses. We identified differentially expressed genes and proteins, related to enterobactin synthesis and virulence establishment, that play important roles in addressing iron scarcity.}, } @article {pmid29864488, year = {2018}, author = {Cesari, AB and Paulucci, NS and Biasutti, MA and Morales, GM and Dardanelli, MS}, title = {Changes in the lipid composition of Bradyrhizobium cell envelope reveal a rapid response to water deficit involving lysophosphatidylethanolamine synthesis from phosphatidylethanolamine in outer membrane.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {303-312}, doi = {10.1016/j.resmic.2018.05.008}, pmid = {29864488}, issn = {1769-7123}, mesh = {Bradyrhizobium/*metabolism ; Cell Membrane/metabolism ; Cell Wall/metabolism ; *Desiccation ; Lysophospholipids/*biosynthesis ; Membrane Fluidity/*drug effects ; Membrane Lipids/*metabolism ; Microscopy, Atomic Force ; Phosphatidylcholines/metabolism ; Phosphatidylethanolamines/metabolism ; Phospholipases/metabolism ; Polyethylene Glycols/*pharmacology ; Water ; }, abstract = {We evaluate the behavior of the membrane of Bradyrhizobium sp. SEMIA6144 during adaptation to polyethylene glycol (PEG). A dehydrating effect on the morphology of the cell surface, as well as a fluidizing effect on the membrane was observed 10 min after PEG shock; however, the bacteria were able to restore optimal membrane fluidity. Shock for 1 h caused an increase of lysophosphatidylethanolamine in the outer membrane at the expense of phosphatidylcholine and phosphatidylethanolamine (PE), through an increase in phospholipase activity. The amount of lysophosphatidylethanolamine did not remain constant during PEG shock, but after 24 h the outer membrane was composed of large amounts of phosphatidylcholine and less amount of lysophosphatidylethanolamine similar to the control. The inner membrane composition was also modified after 1 h of shock, observing an increase of phosphatidylcholine at the expense of PE, the proportions of these phospholipids were then modified to reach 24 h of shock values similar to the control. Vesicles prepared with the lipids of cells exposed to 1 h shock presented higher rigidity compared to the control, indicating that changes in the composition of phospholipids after 1 h of shock restoring fluidity after the PEG effect and would allow cells to maintain surface morphology.}, } @article {pmid29864487, year = {2018}, author = {Ullrich, SR and Poehlein, A and Levicán, G and Mühling, M and Schlömann, M}, title = {Iron targeted transcriptome study draws attention to novel redox protein candidates involved in ferrous iron oxidation in "Ferrovum" sp. JA12.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {618-627}, doi = {10.1016/j.resmic.2018.05.009}, pmid = {29864487}, issn = {1769-7123}, mesh = {Bacterial Proteins/*genetics/metabolism ; Betaproteobacteria/classification/*genetics/isolation & purification/metabolism ; Ferrous Compounds/*metabolism ; Gene Expression Regulation, Bacterial ; Oxidation-Reduction ; Reactive Oxygen Species/metabolism ; Transcriptome ; }, abstract = {The response of the acidophilic iron oxidizer "Ferrovum" sp. JA12 to elevated concentrations of ferrous iron was targeted at transcriptome level in order to assess models on oxidative stress management and ferrous iron oxidation. Overall transcriptome profiles indicate a high cellular activity of "Ferrovum" sp. JA12 up to 50 mM of ferrous iron with genes predicted to be involved in iron oxidation, carbon fixation and ribosome formation showing the highest transcript levels. The data support the iron oxidation pathway inferred from genome analysis and draws attention to further redox proteins potentially associated with iron oxidation. The restriction of homologous proteins to iron oxidizing beta- and zetaproteobacteria underlines the previous notion of a common origin of iron oxidation in these phyla. Detoxification of reactive oxygen species and primary products of oxidative damage of membrane lipids appears to be of permanent relevance under conditions mimicking those of the original habitat of "Ferrovum" sp. JA12. Also the maintenance of a reverse membrane potential appears to be its most important strategy to withstand the acidic external pH.}, } @article {pmid29863457, year = {2018}, author = {Takeshita, K and Tamaki, H and Ohbayashi, T and Meng, XY and Sone, T and Mitani, Y and Peeters, C and Kikuchi, Y and Vandamme, P}, title = {Burkholderia insecticola sp. nov., a gut symbiotic bacterium of the bean bug Riptortus pedestris.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2370-2374}, doi = {10.1099/ijsem.0.002848}, pmid = {29863457}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Burkholderia/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Digestive System/*microbiology ; Fatty Acids/chemistry ; Heteroptera/*microbiology ; Japan ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Symbiosis ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative, aerobic, rod-shaped, non-spore-forming, motile bacterium, designated strain RPE64T, was isolated from the gut symbiotic organ of the bean bug Riptortus pedestris, collected in Tsukuba, Japan, in 2007. 16S rRNA gene sequencing showed that this strain belongs to the Burkholderia glathei clade, exhibiting the highest sequence similarity to Burkholderia peredens LMG 29314T (100 %), Burkholderia turbans LMG 29316T (99.52 %) and Burkholderia ptereochthonis LMG 29326T (99.04 %). Phylogenomic analyses based on 107 single-copy core genes and Genome blast Distance Phylogeny confirmed B. peredens LMG 29314T, B. ptereochthonis LMG 29326T and several uncultivated, endophytic Burkholderia species as its nearest phylogenetic neighbours. Digital DNA-DNA hybridization experiments unambiguously demonstrated that strain RPE64T represents a novel species in this lineage. The G+C content of its genome was 63.2 mol%. The isoprenoid quinone was ubiquinone 8 and the predominant fatty acid components were C16 : 0, C18 : 1ω7c and C17 : 0 cyclo. The absence of nitrate reduction and the capacity to grow at pH 8 clearly differentiated strain RPE64T from related Burkholderia species. Based on these genotypic and phenotypic characteristics, strain RPE64T is classified as representing a novel species of the genus Burkholderia, for which the name Burkholderia insecticola sp. nov. is proposed. The type strain is RPE64T (=NCIMB 15023T=JCM 31142T).}, } @article {pmid29862646, year = {2018}, author = {Durrant, J and Botha, LM and Green, MP and Jones, TM}, title = {Artificial light at night prolongs juvenile development time in the black field cricket, Teleogryllus commodus.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {4}, pages = {225-233}, doi = {10.1002/jez.b.22810}, pmid = {29862646}, issn = {1552-5015}, abstract = {A growing body of evidence exists to support a detrimental effect of the presence of artificial light at night (ALAN) on life-history and fitness traits. However, few studies simultaneously investigate multiple traits and the life stages at which changes manifest. We experimentally manipulated ALAN intensities, within those found in the natural environment, to explore the consequences for growth, survival, and reproductive success of the field cricket, Teleogryllus commodus. We reared crickets from egg to adult under a daily light-cycle consisting of 12 hr bright daylight (2,600 lx) followed by either 12 hr darkness (0 lx) or dim-light environments (1, 10, or 100 lx). We found egg hatch, adult survival, and reproductive measures were largely comparable for all treatments. However, juvenile development time (number of days from egg to adult) was on average 10 days (14%) longer and adults were also larger when crickets were exposed to any light at night (1, 10, or 100 lx). Our data demonstrate that chronic lifetime exposure to ALAN can modulate the timing of life-history events and may disrupt phenology to a similar extent as other abiotic factors.}, } @article {pmid29861885, year = {2018}, author = {Stutz, WE and Blaustein, AR and Briggs, CJ and Hoverman, JT and Rohr, JR and Johnson, PTJ}, title = {Using multi-response models to investigate pathogen coinfections across scales: insights from emerging diseases of amphibians.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {4}, pages = {1109-1120}, pmid = {29861885}, issn = {2041-210X}, support = {R01 GM109499/GM/NIGMS NIH HHS/United States ; }, abstract = {Associations among parasites affect many aspects of host-parasite dynamics, but a lack of analytical tools has limited investigations of parasite correlations in observational data that are often nested across spatial and biological scales.Here we illustrate how hierarchical, multiresponse modeling can characterize parasite associations by allowing for hierarchical structuring, offering estimates of uncertainty, and incorporating correlational model structures. After introducing the general approach, we apply this framework to investigate coinfections among four amphibian parasites (the trematodes Ribeiroia ondatrae and Echinostoma spp., the chytrid fungus Batrachochytrium dendrobatidis, and ranaviruses) and among >2000 individual hosts, 90 study sites, and five amphibian host species.Ninety-two percent of sites and 80% of hosts supported two or more pathogen species. Our results revealed strong correlations between parasite pairs that varied by scale (from among hosts to among sites) and classification (microparasite versus macroparasite), but were broadly consistent across taxonomically diverse host species. At the host-scale, infection by the trematode R. ondatrae correlated positively with the microparasites, B. dendrobatidis and ranavirus, which were themselves positively associated. However, infection by a second trematode (Echinostoma spp.) correlated negatively with B. dendrobatidis and ranavirus, both at the host- and site-level scales, highlighting the importance of differential relationships between micro- and macroparasites.Given the extensive number of coinfecting symbiont combinations inherent to natural systems, particularly across multiple host species, multiresponse modeling of cross-sectional field data offers a valuable tool to identify a tractable number of hypothesized interactions for experimental testing while accounting for uncertainty and potential sources of co-exposure. For amphibians specifically, the high frequency of co-occurrence and coinfection among these pathogens - each of which is known to impair host fitness or survival - highlights the urgency of understanding parasite associations for conservation and disease management.}, } @article {pmid29860865, year = {2018}, author = {Torrance, JS and Kandrik, M and Lee, AJ and DeBruine, LM and Jones, BC}, title = {Does Adult Sex Ratio Predict Regional Variation in Facial Dominance Perceptions? Evidence From an Analysis of U.S. States.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918776748}, doi = {10.1177/1474704918776748}, pmid = {29860865}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Facial Recognition/*physiology ; Female ; *Femininity ; Humans ; Male ; *Masculinity ; *Sex Ratio ; *Social Dominance ; *Social Perception ; United States ; Young Adult ; }, abstract = {When the adult sex ratio of the local population is biased toward women, men face greater costs due to increased direct intrasexual competition. In order to mitigate these costs, men may be more attuned to cues of other men's physical dominance under these conditions. Consequently, we investigated the relationships between the extent to which people (N = 3,586) ascribed high dominance to masculinized versus feminized faces and variation in adult sex ratio across U.S. states. Linear mixed models showed that masculinized faces were perceived as more dominant than feminized faces, particularly for judgments of men's facial dominance. Dominance perceptions were weakly related to adult sex ratio, and this relationship was not moderated by face sex, participant sex, or their interaction. Thus, our results suggest that dominance perceptions are relatively unaffected by broad geographical differences in adult sex ratios.}, } @article {pmid29860531, year = {2018}, author = {Liang, B and Wang, N and Li, N and Kimball, RT and Braun, EL}, title = {Comparative Genomics Reveals a Burst of Homoplasy-Free Numt Insertions.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2060-2064}, doi = {10.1093/molbev/msy112}, pmid = {29860531}, issn = {1537-1719}, abstract = {Mitochondrial DNA sequences are frequently transferred into the nuclear genome, giving rise to numts (nuclear mitochondrial DNA segments). In the absence of whole genomes, avian numts have been suggested to be rare and relatively short. We examined 64 bird genomes to test hypotheses regarding numt frequency, distribution among taxa, and likelihood of homoplasy. We discovered 100-fold variation in numt number across species. Two songbirds, Geospiza fortis (Darwin's finch) and Zonotrichia albicollis (white-throated sparrow) had the largest number of numts. Ancestral state reconstruction of 957 numt insertions in these two species and their close relatives indicated a remarkable acceleration of numt insertion in the ancestor of Geospiza and Zonotrichia followed by slower, continued accumulation in each lineage. These numts appear to result primarily from de novo insertion with the duplication of existing numts representing a secondary pathway. Insertion events were essentially homoplasy-free and numts appear to represent perfect rare genomic changes.}, } @article {pmid29860412, year = {2018}, author = {Weglarz, KM and Havill, NP and Burke, GR and von Dohlen, CD}, title = {Partnering With a Pest: Genomes of Hemlock Woolly Adelgid Symbionts Reveal Atypical Nutritional Provisioning Patterns in Dual-Obligate Bacteria.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1607-1621}, pmid = {29860412}, issn = {1759-6653}, mesh = {Animals ; Bacteria/*genetics ; Hemiptera/*genetics ; Insecta/genetics ; Introduced Species ; Phylogeny ; Tsuga/*parasitology ; }, abstract = {Nutritional bacterial symbionts enhance the diets of sap-feeding insects with amino acids and vitamins missing from their diets. In many lineages, an ancestral senior symbiont is joined by a younger junior symbiont. To date, an emergent pattern is that senior symbionts supply a majority of amino acids, and junior symbionts supply a minority. Similar to other hemipterans, adelgids harbor obligate symbionts, but have higher diversity of bacterial associates, suggesting a history of symbiont turnover. The metabolic roles of dual symbionts in adelgids and their contributions to the consortium are largely unexplored. Here, we investigate the symbionts of Adelges tsugae, the hemlock woolly adelgid (HWA), an invasive species introduced from Japan to the eastern United States, where it kills hemlock trees. The response of hemlocks to HWA feeding has aspects of a defensive reaction against pathogens, and some have speculated that symbionts may be involved. We sequenced the genomes of "Ca. Annandia adelgestsuga" and "Ca. Pseudomonas adelgestsugas" symbionts to detail their metabolic capabilities, infer ages of relationship, and search for effectors of plant defenses. We also tested the relationship of "Ca. Annandia" to symbionts of other insects. We find that both symbionts provide nutrients, but in more balanced proportions than dual symbionts of other hemipterans. The lesser contributions of the senior "Ca. Annandia" support our hypothesis for symbiont replacements in adelgids. Phylogenomic results were ambiguous regarding the position of "Ca. Annandia". We found no obvious effectors of plant defenses related to insect virulence, but hypothetical proteins in symbionts are unknown players.}, } @article {pmid29860403, year = {2018}, author = {Mueller, LD and Phillips, MA and Barter, TT and Greenspan, ZS and Rose, MR}, title = {Genome-Wide Mapping of Gene-Phenotype Relationships in Experimentally Evolved Populations.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2085-2095}, doi = {10.1093/molbev/msy113}, pmid = {29860403}, issn = {1537-1719}, abstract = {Model organisms subjected to sustained experimental evolution often show levels of phenotypic differentiation that dramatically exceed the phenotypic differences observed in natural populations. Genome-wide sequencing of pooled populations then offers the opportunity to make inferences about the genes that are the cause of these phenotypic differences. We tested, through computer simulations, the efficacy of a statistical learning technique called the "fused lasso additive model" (FLAM). We focused on the ability of FLAM to distinguish between genes which are differentiated and directly affect a phenotype from differentiated genes which have no effect on the phenotype. FLAM can separate these two classes of genes even with relatively small samples (10 populations, in total). The efficacy of FLAM is improved with increased number of populations, reduced environmental phenotypic variation, and increased within-treatment among-replicate variation. FLAM was applied to SNP variation measured in both twenty-population and thirty-population studies of Drosophila subjected to selection for age-at-reproduction, to illustrate the application of the method.}, } @article {pmid29860351, year = {2018}, author = {Wong, DK and Grisdale, CJ and Fast, NM}, title = {Evolution and Diversity of Pre-mRNA Splicing in Highly Reduced Nucleomorph Genomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1573-1583}, pmid = {29860351}, issn = {1759-6653}, mesh = {Cell Nucleus/*genetics ; Cercozoa/genetics ; Chlorophyta/genetics ; Cryptophyta/genetics ; Eukaryota/genetics ; Evolution, Molecular ; Gene Regulatory Networks/genetics ; Genetic Variation/*genetics ; Genome/*genetics ; Introns/genetics ; Plastids/genetics ; RNA Precursors/*genetics ; RNA Splicing/*genetics ; RNA, Antisense/genetics ; Transcription, Genetic/genetics ; Transcriptome/genetics ; }, abstract = {Eukaryotic genes are interrupted by introns that are removed in a conserved process known as pre-mRNA splicing. Though well-studied in select model organisms, we are only beginning to understand the variation and diversity of this process across the tree of eukaryotes. We explored pre-mRNA splicing and other features of transcription in nucleomorphs, the highly reduced remnant nuclei of secondary endosymbionts. Strand-specific transcriptomes were sequenced from the cryptophyte Guillardia theta and the chlorarachniophyte Bigelowiella natans, whose plastids are derived from red and green algae, respectively. Both organisms exhibited elevated nucleomorph antisense transcription and gene expression relative to their respective nuclei, suggesting unique properties of gene regulation and transcriptional control in nucleomorphs. Marked differences in splicing were observed between the two nucleomorphs: the few introns of the G. theta nucleomorph were largely retained in mature transcripts, whereas the many short introns of the B. natans nucleomorph are spliced at typical eukaryotic levels (>90%). These differences in splicing levels could be reflecting the ancestries of the respective plastids, the different intron densities due to independent genome reduction events, or a combination of both. In addition to extending our understanding of the diversity of pre-mRNA splicing across eukaryotes, our study also indicates potential links between splicing, antisense transcription, and gene regulation in reduced genomes.}, } @article {pmid29860336, year = {2018}, author = {Deitz, KC and Takken, W and Slotman, MA}, title = {The Effect of Hybridization on Dosage Compensation in Member Species of the Anopheles gambiae Species Complex.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1663-1672}, pmid = {29860336}, issn = {1759-6653}, mesh = {Animals ; Anopheles/*genetics ; *Chromosomes, Insect/genetics ; *Dosage Compensation, Genetic ; Female ; Gene Expression ; Genes, Insect ; *Hybridization, Genetic ; Male ; Sequence Analysis, RNA ; X Chromosome/genetics ; Y Chromosome/genetics ; }, abstract = {Dosage compensation has evolved in concert with Y-chromosome degeneration in many taxa that exhibit heterogametic sex chromosomes. Dosage compensation overcomes the biological challenge of a "half dose" of X chromosome gene transcripts in the heterogametic sex. The need to equalize gene expression of a hemizygous X with that of autosomes arises from the fact that the X chromosomes retain hundreds of functional genes that are actively transcribed in both sexes and interact with genes expressed on the autosomes. Sex determination and heterogametic sex chromosomes have evolved multiple times in Diptera, and in each case the genetic control of dosage compensation is tightly linked to sex determination. In the Anopheles gambiae species complex (Culicidae), maleness is conferred by the Y-chromosome gene Yob, which despite its conserved role between species is polymorphic in its copy number between them. Previous work demonstrated that male An. gambiae s.s. males exhibit complete dosage compensation in pupal and adult stages. In the present study, we have extended this analysis to three sister species in the An. gambiae complex: An. coluzzii, An. arabiensis, and An. quadriannulatus. In addition, we analyzed dosage compensation in bi-directional F1 hybrids between these species to determine if hybridization results in the mis-regulation and disruption of dosage compensation. Our results confirm that dosage compensation operates in the An. gambiae species complex through the hypertranscription of the male X chromosome. Additionally, dosage compensation in hybrid males does not differ from parental males, indicating that hybridization does not result in the mis-regulation of dosage compensation.}, } @article {pmid29860323, year = {2018}, author = {vonHoldt, BM and Ji, SS and Aardema, ML and Stahler, DR and Udell, MAR and Sinsheimer, JS}, title = {Activity of Genes with Functions in Human Williams-Beuren Syndrome Is Impacted by Mobile Element Insertions in the Gray Wolf Genome.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1546-1553}, pmid = {29860323}, issn = {1759-6653}, support = {R01 GM053275/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; DNA Transposable Elements/*genetics ; Dogs ; Epigenesis, Genetic/genetics ; Gene Dosage/genetics ; Gene Expression Regulation/genetics ; Gene Silencing/physiology ; Humans ; Methylation ; Transcription, Genetic/genetics ; Transcriptome/genetics ; Williams Syndrome/*genetics ; Wolves/*genetics ; }, abstract = {In canines, transposon dynamics have been associated with a hyper-social behavioral syndrome, although the functional mechanism has yet to be described. We investigate the epigenetic and transcriptional consequences of these behavior-associated mobile element insertions (MEIs) in dogs and Yellowstone gray wolves. We posit that the transposons themselves may not be the causative feature; rather, their transcriptional regulation may exert the functional impact. We survey four outlier transposons associated with hyper-sociability, with the expectation that they are targeted for epigenetic silencing. We predict hyper-methylation of MEIs, suggestive that the epigenetic silencing of and not the MEIs themselves may be driving dysregulation of nearby genes. We found that transposon-derived sequences are significantly hyper-methylated, regardless of their copy number or species. Further, we have assessed transcriptome sequence data and found evidence that MEIs impact the expression levels of six genes (WBSCR17, LIMK1, GTF2I, WBSCR27, BAZ1B, and BCL7B), all of which have known roles in human Williams-Beuren syndrome due to changes in copy number, typically hemizygosity. Although further evidence is needed, our results suggest that a few insertions alter local expression at multiple genes, likely through a cis-regulatory mechanism that excludes proximal methylation.}, } @article {pmid29860303, year = {2018}, author = {Cacheux, L and Ponger, L and Gerbault-Seureau, M and Loll, F and Gey, D and Richard, FA and Escudé, C}, title = {The Targeted Sequencing of Alpha Satellite DNA in Cercopithecus pogonias Provides New Insight Into the Diversity and Dynamics of Centromeric Repeats in Old World Monkeys.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1837-1851}, pmid = {29860303}, issn = {1759-6653}, mesh = {Animals ; Base Sequence ; Centromere/*genetics ; Cercopithecidae/genetics ; Cercopithecus/*genetics ; Consensus Sequence ; DNA, Satellite/*genetics ; Evolution, Molecular ; In Situ Hybridization, Fluorescence ; Karyotype ; Male ; Minisatellite Repeats ; Sequence Analysis, DNA ; }, abstract = {Alpha satellite is the major repeated DNA element of primate centromeres. Specific evolutionary mechanisms have led to a great diversity of sequence families with peculiar genomic organization and distribution, which have till now been studied mostly in great apes. Using high throughput sequencing of alpha satellite monomers obtained by enzymatic digestion followed by computational and cytogenetic analysis, we compare here the diversity and genomic distribution of alpha satellite DNA in two related Old World monkey species, Cercopithecus pogonias and Cercopithecus solatus, which are known to have diverged about 7 Ma. Two main families of monomers, called C1 and C2, are found in both species. A detailed analysis of our data sets revealed the existence of numerous subfamilies within the centromeric C1 family. Although the most abundant subfamily is conserved between both species, our fluorescence in situ hybridization (FISH) experiments clearly show that some subfamilies are specific for each species and that their distribution is restricted to a subset of chromosomes, thereby pointing to the existence of recurrent amplification/homogenization events. The pericentromeric C2 family is very abundant on the short arm of all acrocentric chromosomes in both species, pointing to specific mechanisms that lead to this distribution. Results obtained using two different restriction enzymes are fully consistent with a predominant monomeric organization of alpha satellite DNA that coexists with higher order organization patterns in the C. pogonias genome. Our study suggests a high dynamics of alpha satellite DNA in Cercopithecini, with recurrent apparition of new sequence variants and interchromosomal sequence transfer.}, } @article {pmid29860283, year = {2018}, author = {Tsai, YM and Chang, A and Kuo, CH}, title = {Horizontal Gene Acquisitions Contributed to Genome Expansion in Insect-Symbiotic Spiroplasma clarkii.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1526-1532}, pmid = {29860283}, issn = {1759-6653}, mesh = {Animals ; Carbohydrates/genetics ; DNA, Bacterial/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome Size/genetics ; Genome, Bacterial/*genetics ; Insecta/*microbiology ; Phylogeny ; Spiroplasma/*growth & development ; Symbiosis/*genetics ; }, abstract = {Genome reduction is a recurring theme of symbiont evolution. The genus Spiroplasma contains species that are mostly facultative insect symbionts. The typical genome sizes of those species within the Apis clade were estimated to be ∼1.0-1.4 Mb. Intriguingly, Spiroplasma clarkii was found to have a genome size that is >30% larger than the median of other species within the same clade. To investigate the molecular evolution events that led to the genome expansion of this bacterium, we determined its complete genome sequence and inferred the evolutionary origin of each protein-coding gene based on the phylogenetic distribution of homologs. Among the 1,346 annotated protein-coding genes, 641 were originated from within the Apis clade while 233 were putatively acquired from outside of the clade (including 91 high-confidence candidates). Additionally, 472 were specific to S. clarkii without homologs in the current database (i.e., the origins remained unknown). The acquisition of protein-coding genes, rather than mobile genetic elements, appeared to be a major contributing factor of genome expansion. Notably, >50% of the high-confidence acquired genes are related to carbohydrate transport and metabolism, suggesting that these acquired genes contributed to the expansion of both genome size and metabolic capability. The findings of this work provided an interesting case against the general evolutionary trend observed among symbiotic bacteria and further demonstrated the flexibility of Spiroplasma genomes. For future studies, investigation on the functional integration of these acquired genes, as well as the inference of their contribution to fitness could improve our knowledge of symbiont evolution.}, } @article {pmid29860278, year = {2018}, author = {Kinjo, Y and Bourguignon, T and Tong, KJ and Kuwahara, H and Lim, SJ and Yoon, KB and Shigenobu, S and Park, YC and Nalepa, CA and Hongoh, Y and Ohkuma, M and Lo, N and Tokuda, G}, title = {Parallel and Gradual Genome Erosion in the Blattabacterium Endosymbionts of Mastotermes darwiniensis and Cryptocercus Wood Roaches.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1622-1630}, pmid = {29860278}, issn = {1759-6653}, mesh = {Animals ; Cockroaches/*genetics ; Flavobacteriaceae/*genetics ; Genome, Bacterial/*genetics ; Isoptera/*microbiology ; Phylogeny ; Symbiosis/*genetics ; Wood/*microbiology ; }, abstract = {Almost all examined cockroaches harbor an obligate intracellular endosymbiont, Blattabacterium cuenoti. On the basis of genome content, Blattabacterium has been inferred to recycle nitrogen wastes and provide amino acids and cofactors for its hosts. Most Blattabacterium strains sequenced to date harbor a genome of ∼630 kbp, with the exception of the termite Mastotermes darwiniensis (∼590 kbp) and Cryptocercus punctulatus (∼614 kbp), a representative of the sister group of termites. Such genome reduction may have led to the ultimate loss of Blattabacterium in all termites other than Mastotermes. In this study, we sequenced 11 new Blattabacterium genomes from three species of Cryptocercus in order to shed light on the genomic evolution of Blattabacterium in termites and Cryptocercus. All genomes of Cryptocercus-derived Blattabacterium genomes were reduced (∼614 kbp), except for that associated with Cryptocercus kyebangensis, which comprised 637 kbp. Phylogenetic analysis of these genomes and their content indicates that Blattabacterium experienced parallel genome reduction in Mastotermes and Cryptocercus, possibly due to similar selective forces. We found evidence of ongoing genome reduction in Blattabacterium from three lineages of the C. punctulatus species complex, which independently lost one cysteine biosynthetic gene. We also sequenced the genome of the Blattabacterium associated with Salganea taiwanensis, a subsocial xylophagous cockroach that does not vertically transmit gut symbionts via proctodeal trophallaxis. This genome was 632 kbp, typical of that of nonsubsocial cockroaches. Overall, our results show that genome reduction occurred on multiple occasions in Blattabacterium, and is still ongoing, possibly because of new associations with gut symbionts in some lineages.}, } @article {pmid29860258, year = {2018}, author = {Montiel, JF and Aboitiz, F}, title = {Homology in Amniote Brain Evolution: The Rise of Molecular Evidence.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {2}, pages = {59-64}, doi = {10.1159/000489116}, pmid = {29860258}, issn = {1421-9743}, } @article {pmid29860101, year = {2018}, author = {Johnson, AJ and McKenna, DD and Jordal, BH and Cognato, AI and Smith, SM and Lemmon, AR and Lemmon, EM and Hulcr, J}, title = {Phylogenomics clarifies repeated evolutionary origins of inbreeding and fungus farming in bark beetles (Curculionidae, Scolytinae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {229-238}, doi = {10.1016/j.ympev.2018.05.028}, pmid = {29860101}, issn = {1095-9513}, abstract = {Bark and ambrosia beetles (Curculionidae, Scolytinae) display a conspicuous diversity of unusual genetic and ecological attributes and behaviors. Reconstructing the evolution of Scolytinae, particularly the large and ecologically significant tribe Cryphalini (pygmy borers), has long been problematic. These challenges have not adequately been addressed using morphological characters, and previous research has used only DNA sequence data from small numbers of genes. Through a combination of anchored hybrid enrichment, low-coverage draft genomes, and transcriptomes, we addressed these challenges by amassing a large molecular phylogenetic dataset for bark and ambrosia beetles. The resulting DNA sequence data from 251 protein coding genes (114,276 bp of nucleotide sequence data) support inference of the first robust phylogeny of Scolytinae, with a special focus on the species rich tribe Cryphalini and its close relatives. Key strategies, including inbreeding mating systems and fungus farming, evolved repeatedly across Scolytinae. We confirm 12 of 16 hypothesized origins of fungus farming, 6 of 8 origins of inbreeding polygyny and at least 11 independent origins of a super-generalist host range. These three innovations are statistically correlated, but their appearance within lineages was not necessarily simultaneous. Additionally, the evolution of extreme host plant generalism often preceded, rather than succeeded, fungus farming. Of the high-diversity tribes of Scolytinae, only Xyleborini is monophyletic, Corthylini is paraphyletic and Cryphalini is highly polyphyletic. Cryphalini sensu stricto is part of a clade containing the genera Hypothenemus, Cryphalus and Trypophloeus, and the tribe Xyloterini. Stegomerus and Cryptocarenus (Cryphalini) are part of a clade otherwise containing all Corthylini. Several other genera, including Ernoporus and Scolytogenes (Cryphalini), make up a distantly related clade. Several of the genera of Cryphalini are also intermixed. For example, Cryphalus and Hypocryphalus are intermingled, as well as Ernoporicus, Ptilopodius and Scolytogenes. Our data are consistent with widespread polyphyly and paraphyly across Scolytinae and within Cryphalini, and provides new insights into the evolution of inbreeding mating systems and fungus farming in the species rich and ecologically significant weevil subfamily Scolytinae.}, } @article {pmid29859892, year = {2018}, author = {Yang, Y and Li, Y and Gao, T and Zhang, Y and Wang, Q}, title = {C-di-GMP turnover influences motility and biofilm formation in Bacillus amyloliquefaciens PG12.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {205-213}, doi = {10.1016/j.resmic.2018.04.009}, pmid = {29859892}, issn = {1769-7123}, mesh = {3',5'-Cyclic-GMP Phosphodiesterases/*genetics/metabolism ; Bacillus amyloliquefaciens/genetics/*metabolism ; Biofilms/growth & development ; Biological Control Agents ; Cyclic GMP/*analogs & derivatives/metabolism ; Escherichia coli Proteins/*genetics/metabolism ; Gene Expression Regulation, Bacterial/*genetics ; Gene Knockout Techniques ; Movement ; Phosphorus-Oxygen Lyases/*genetics/metabolism ; Signal Transduction/genetics ; }, abstract = {Bis-(3'→5') cyclic dimeric guanosine monophosphate (c-di-GMP) is defined as a highly versatile secondary messenger in bacteria, coordinating diverse aspects of bacterial growth and behavior, including motility and biofilm formation. Bacillus amyloliquefaciens PG12 is an effective biocontrol agent against apple ring rot caused by Botryosphaeria dothidea. In this study, we characterized the core regulators of c-di-GMP turnover in B. amyloliquefaciens PG12. Using bioinformatic analysis, heterologous expression and biochemical characterization of knockout and overexpression derivatives, we identified and characterized two active diguanylate cyclases (which catalyze c-di-GMP biosynthesis), YhcK and YtrP and one active c-di-GMP phosphodiesterase (which degrades c-di-GMP), YuxH. Furthermore, we showed that elevating c-di-GMP levels up to a certain threshold inhibited the swimming motility of B. amyloliquefaciens PG12. Although yhcK, ytrP and yuxH knockout mutants did not display defects in biofilm formation, significant increases in c-di-GMP levels induced by YtrP or YuxH overexpression stimulated biofilm formation in B. amyloliquefaciens PG12. Our results indicate that B. amyloliquefaciens possesses a functional c-di-GMP signaling system that influences the bacterium's motility and ability to form biofilms. Since motility and biofilm formation influence the efficacy of biological control agent, our work provides a basis for engineering a more effective strain of B. amyloliquefaciens PG12.}, } @article {pmid29859890, year = {2018}, author = {Sittewelle, M and Monsoro-Burq, AH}, title = {AKT signaling displays multifaceted functions in neural crest development.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.05.023}, pmid = {29859890}, issn = {1095-564X}, abstract = {AKT signaling is an essential intracellular pathway controlling cell homeostasis, cell proliferation and survival, as well as cell migration and differentiation in adults. Alterations impacting the AKT pathway are involved in many pathological conditions in human disease. Similarly, during development, multiple transmembrane molecules, such as FGF receptors, PDGF receptors or integrins, activate AKT to control embryonic cell proliferation, migration, differentiation, and also cell fate decisions. While many studies in mouse embryos have clearly implicated AKT signaling in the differentiation of several neural crest derivatives, information on AKT functions during the earliest steps of neural crest development had remained relatively scarce until recently. However, recent studies on known and novel regulators of AKT signaling demonstrate that this pathway plays critical roles throughout the development of neural crest progenitors. Non-mammalian models such as fish and frog embryos have been instrumental to our understanding of AKT functions in neural crest development, both in neural crest progenitors and in the neighboring tissues. This review combines current knowledge acquired from all these different vertebrate animal models to describe the various roles of AKT signaling related to neural crest development in vivo. We first describe the importance of AKT signaling in patterning the tissues involved in neural crest induction, namely the dorsal mesoderm and the ectoderm. We then focus on AKT signaling functions in neural crest migration and differentiation.}, } @article {pmid29859889, year = {2018}, author = {Da Silva, F and Massa, F and Motamedi, FJ and Vidal, V and Rocha, AS and Gregoire, EP and Cai, CL and Wagner, KD and Schedl, A}, title = {Myocardial-specific R-spondin3 drives proliferation of the coronary stems primarily through the Leucine Rich Repeat G Protein coupled receptor LGR4.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {42-51}, doi = {10.1016/j.ydbio.2018.05.024}, pmid = {29859889}, issn = {1095-564X}, support = {R56 HL129807/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Coronary Circulation/physiology ; Coronary Vessels/cytology/*embryology ; Heart/*embryology ; Mice ; Mice, Transgenic ; Myocytes, Cardiac/cytology/*metabolism ; Receptors, G-Protein-Coupled/genetics/*metabolism ; Thrombospondins/genetics/*metabolism ; Wnt Signaling Pathway/*physiology ; }, abstract = {Coronary artery anomalies are common congenital disorders with serious consequences in adult life. Coronary circulation begins when the coronary stems form connections between the aorta and the developing vascular plexus. We recently identified the WNT signaling modulator R-spondin 3 (Rspo3), as a crucial regulator of coronary stem proliferation. Using expression analysis and tissue-specific deletion we now demonstrate that Rspo3 is primarily produced by cardiomyocytes. Moreover, we have employed CRISPR/Cas9 technology to generate novel Lgr4-null alleles that showed a significant decrease in coronary stem proliferation and thus phenocopied the coronary artery defects seen in Rspo3 mutants. Interestingly, Lgr4 mutants displayed slightly hypomorphic right ventricles, an observation also made after myocardial specific deletion of Rspo3. These results shed new light on the role of Rspo3 in heart development and demonstrate that LGR4 is the principal R-spondin 3 receptor in the heart.}, } @article {pmid29859088, year = {2018}, author = {Domènech, A and Ayté, J and Antunes, F and Hidalgo, E}, title = {Using in vivo oxidation status of one- and two-component redox relays to determine H2O2 levels linked to signaling and toxicity.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {61}, pmid = {29859088}, issn = {1741-7007}, abstract = {BACKGROUND: Hydrogen peroxide (H2O2) is generated as a by-product of metabolic reactions during oxygen use by aerobic organisms, and can be toxic or participate in signaling processes. Cells, therefore, need to be able to sense and respond to H2O2 in an appropriate manner. This is often accomplished through thiol switches: Cysteine residues in proteins that can act as sensors, and which are both scarce and finely tuned. Bacteria and eukaryotes use different types of such sensors-either a one-component (OxyR) or two-component (Pap1-Tpx1) redox relay, respectively. However, the biological significance of these two different signaling modes is not fully understood, and the concentrations and peroxides driving those types of redox cascades have not been determined, nor the intracellular H2O2 levels linked to toxicity. Here we elucidate the characteristics, rates, and dynamic ranges of both systems.

RESULTS: By comparing the activation of both systems in fission yeast, and applying mathematical equations to the experimental data, we estimate the toxic threshold of intracellular H2O2 able to halt aerobic growth, and the temporal gradients of extracellular to intracellular peroxides. By calculating both the oxidation rates of OxyR and Tpx1 by peroxides, and their reduction rates by the cellular redoxin systems, we propose that, while Tpx1 is a sensor and an efficient H2O2 scavenger because it displays fast oxidation and reduction rates, OxyR is strictly a H2O2 sensor, since its reduction kinetics are significantly slower than its oxidation by peroxides, and therefore, it remains oxidized long enough to execute its transcriptional role. We also show that these two paradigmatic H2O2-sensing models are biologically similar at pre-toxic peroxide levels, but display strikingly different activation behaviors at toxic doses.

CONCLUSIONS: Both Tpx1 and OxyR contain thiol switches, with very high reactivity towards peroxides. Nevertheless, the fast reduction of Tpx1 defines it as a scavenger, and this efficient recycling dramatically changes the Tpx1-Pap1 response to H2O2 and connects H2O2 sensing to the redox state of the cell. In contrast, OxyR is a true H2O2 sensor but not a scavenger, being partially insulated from the cellular electron donor capacity.}, } @article {pmid29859055, year = {2018}, author = {Han, M and Song, Y and Qian, J and Ming, D}, title = {Sequence-based prediction of physicochemical interactions at protein functional sites using a function-and-interaction-annotated domain profile database.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {204}, pmid = {29859055}, issn = {1471-2105}, abstract = {BACKGROUND: Identifying protein functional sites (PFSs) and, particularly, the physicochemical interactions at these sites is critical to understanding protein functions and the biochemical reactions involved. Several knowledge-based methods have been developed for the prediction of PFSs; however, accurate methods for predicting the physicochemical interactions associated with PFSs are still lacking.

RESULTS: In this paper, we present a sequence-based method for the prediction of physicochemical interactions at PFSs. The method is based on a functional site and physicochemical interaction-annotated domain profile database, called fiDPD, which was built using protein domains found in the Protein Data Bank. This method was applied to 13 target proteins from the very recent Critical Assessment of Structure Prediction (CASP10/11), and our calculations gave a Matthews correlation coefficient (MCC) value of 0.66 for PFS prediction and an 80% recall in the prediction of the associated physicochemical interactions.

CONCLUSIONS: Our results show that, in addition to the PFSs, the physical interactions at these sites are also conserved in the evolution of proteins. This work provides a valuable sequence-based tool for rational drug design and side-effect assessment. The method is freely available and can be accessed at http://202.119.249.49 .}, } @article {pmid29859051, year = {2018}, author = {Choudhri, P and Rani, M and Sangwan, RS and Kumar, R and Kumar, A and Chhokar, V}, title = {De novo sequencing, assembly and characterisation of Aloe vera transcriptome and analysis of expression profiles of genes related to saponin and anthraquinone metabolism.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {427}, pmid = {29859051}, issn = {1471-2164}, support = {F: 41-586/2012(SR)//University Grants Commission/ ; }, mesh = {Aloe/*genetics/*metabolism ; Anthraquinones/*metabolism ; *Gene Expression Profiling ; Genes, Plant/*genetics ; Genomics ; Molecular Sequence Annotation ; Saponins/*metabolism ; *Sequence Analysis ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: Aloe vera is a perennial, succulent, drought-resistant plant that exhibits many pharmacological characteristics such as wound healing ability against skin burns, anti-ulcer, anti-inflammatory, anti-tumor, anti-viral, anti-hypercholesterolemic, anti-hyperglycemic, anti-asthmatic and much more. Despite great medicinal worth, little genomic information is available on Aloe vera. This study is an initiative to explore the full-scale functional genomics of Aloe vera by generating whole transcriptome sequence database, using Illumina HiSeq technology and its progressive annotation specifically with respect to the metabolic specificity of the plant.

RESULTS: Transcriptome sequencing of root and leaf tissue of Aloe vera was performed using Illumina paired-end sequencing technology. De novo assembly of high quality paired-end reads, resulted into 1,61,733 and 2,21,792 transcripts with mean length of 709 and 714 nucleotides for root and leaf respectively. The non-redundant transcripts were clustered using CD-HIT-EST, yielding a total of 1,13,063 and 1,41,310 unigenes for root and leaf respectively. A total of 6114 and 6527 CDS for root and leaf tissue were enriched into 24 different biological pathway categories using KEGG pathway database. DGE profile prepared by calculating FPKM values was analyzed for differential expression of specific gene encoding enzymes involved in secondary metabolite biosynthesis. Sixteen putative genes related to saponin, lignin, anthraquinone, and carotenoid biosynthesis were selected for quantitative expression by real-time PCR. DGE as well as qRT PCR expression analysis represented up-regulation of secondary metabolic genes in root as compared to leaf. Furthermore maximum number of genes was found to be up-regulated after the induction of methyl jasmonate, which stipulates the association of secondary metabolite synthesis with the plant's defense mechanism during stress. Various transcription factors including bHLH, NAC, MYB were identified by searching predicted CDS against PlantTFdb.

CONCLUSIONS: This is the first transcriptome database of Aloe vera and can be potentially utilized to characterize the genes involved in the biosynthesis of important secondary metabolites, metabolic regulation, signal transduction mechanism, understanding function of a particular gene in the biology and physiology of plant of this species as well as other species of Aloe genus.}, } @article {pmid29859049, year = {2018}, author = {Chang, KW and Tseng, YT and Chen, YC and Yu, CY and Liao, HF and Chen, YC and Tu, YE and Wu, SC and Liu, IH and Pinskaya, M and Morillon, A and Pain, B and Lin, SP}, title = {Stage-dependent piRNAs in chicken implicated roles in modulating male germ cell development.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {425}, pmid = {29859049}, issn = {1471-2164}, support = {102-2314-B-002-070-MY3//Ministry of Science and Technology, Taiwan (TW)/ ; 106-2311-B-002-009-//Ministry of Science and Technology, Taiwan (TW)/ ; 101R7602D3//National Taiwan University/ ; 102R7602D3//National Taiwan University/ ; 103R7602D3//National Taiwan University/ ; REGULncRNA, DNA-Life//Agence Nationale de la Recherche/ ; ANR-10-EQPX-03//Agence Nationale de la Recherche/ ; ANR10-INBS-09-08//Agence Nationale de la Recherche/ ; Consolidator Grant (CoG), LS2, ERC-2013-CoG//European Research Council/International ; CRB-ANIM-ANR-11-INBS-0003//Agence Nationale de la Recherche (FR)/ ; 106AS-2.2.2-AD-U1(Z)//Council of Agriculture/ ; }, mesh = {Animals ; Cell Lineage/genetics ; Chickens/*genetics ; DNA Transposable Elements/genetics ; Male ; RNA, Small Interfering/*genetics ; Spermatozoa/*cytology/metabolism ; }, abstract = {BACKGROUND: The PIWI/piRNA pathway is a conserved machinery important for germ cell development and fertility. This piRNA-guided molecular machinery is best known for repressing derepressed transposable elements (TE) during epigenomic reprogramming. The extent to which piRNAs are involved in modulating transcripts beyond TEs still need to be clarified, and it may be a stage-dependent event. We chose chicken germline as a study model because of the significantly lower TE complexity in the chicken genome compared to mammalian species.

RESULTS: We generated high-confidence piRNA candidates in various stages across chicken germline development by 3'-end-methylation-enriched small RNA sequencing and in-house bioinformatics analysis. We observed a significant developmental stage-dependent loss of TE association and a shifting of the ping-pong cycle signatures. Moreover, the stage-dependent reciprocal abundance of LINE retrotransposons, CR1-C, and its associated piRNAs implicated the developmental stage-dependent role of piRNA machinery. The stage dependency of piRNA expression and its potential functions can be better addressed by analyzing the piRNA precursors/clusters. Interestingly, the new piRNA clusters identified from embryonic chicken testes revealed evolutionary conservation between chickens and mammals, which was previously thought to not exist.

CONCLUSIONS: In this report, we provided an original chicken RNA resource and proposed an analytical methodology that can be used to investigate stage-dependent changes in piRNA compositions and their potential roles in TE regulation and beyond, and also revealed possible conserved functions of piRNAs in developing germ cells.}, } @article {pmid29859043, year = {2018}, author = {Chai, L and Chai, P and Chen, S and Flaishman, MA and Ma, H}, title = {Transcriptome analysis unravels spatiotemporal modulation of phytohormone-pathway expression underlying gibberellin-induced parthenocarpic fruit set in San Pedro-type fig (Ficus carica L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {100}, pmid = {29859043}, issn = {1471-2229}, support = {NSFC [31372007]//National Natural Science Foundation of China/ ; }, mesh = {Down-Regulation ; Ficus/*genetics/growth & development/physiology ; Flowers/genetics/growth & development/physiology ; Fruit/genetics/growth & development/physiology ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Gibberellins/*metabolism ; Plant Growth Regulators/*metabolism ; Signal Transduction ; *Transcriptome ; Up-Regulation ; }, abstract = {BACKGROUND: Gibberellin (GA) treatments can induce parthenocarpy in the main crop of San Pedro-type figs, the native non-parthenocarpic fruit, however, the underlying mechanism is still largely unclear.

RESULTS: In our study, GA3 was applied to San Pedro-type fig main crop at anthesis. Sharply increased GA3 content was detected in both female flowers and receptacle, along with significantly decreased indole-3-acetic acid (IAA), zeatin and abscisic acid (ABA) levels in female flowers, and increased zeatin peak intensity and earlier ABA peak in receptacles. Transcriptome comparison between control and treatment groups identified more differentially expressed genes (DEGs) in receptacles than in female flowers 2 and 4 days after treatment (DAT); 10 DAT, the number of DEGs became similar in the two tissues. Synchronized changing trends of phytohormone-associated DEGs were observed in female flowers and receptacles with fruit development. Modulation of ethylene and GA signaling and auxin metabolism by exogenous GA3 occurred mainly 2 DAT, whereas changes in auxin, cytokinin and ABA signaling occurred mainly 10 DAT. Auxin-, ethylene- and ABA-metabolism and response pathways were largely regulated in the two tissues, mostly 2 and 10 DAT. The major components altering fig phytohormone metabolic and response patterns included downregulated GA2ox, BAS1, NCED and ACO, and upregulated ABA 8'-h and AUX/IAA.

CONCLUSIONS: Thus GA-induced parthenocarpy in fig is co-modulated by the female flowers and receptacle, and repression of ABA and ethylene biosynthesis and GA catabolism might be the main forces deflecting abscission and producing fig parthenocarpy.}, } @article {pmid29859042, year = {2018}, author = {Schulte, A and Schilling, JV and Nolten, J and Korona, A and Krömke, H and Vennekötter, JB and Schillheim, B and Wessling, M and Conrath, U and Büchs, J}, title = {Parallel online determination of ethylene release rate by Shaken Parsley cell cultures using a modified RAMOS device.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {101}, pmid = {29859042}, issn = {1471-2229}, mesh = {Acetates/metabolism ; Calibration ; Cells, Cultured ; Cyclopentanes/metabolism ; Ethylenes/*analysis/metabolism ; Online Systems ; Oxidation-Reduction ; Oxygen/metabolism ; Oxylipins/metabolism ; Petroselinum/*metabolism ; Plant Growth Regulators/*analysis/metabolism ; Salicylates/metabolism ; }, abstract = {BACKGROUND: Ethylene is an important plant hormone that controls many physiological processes in plants. Conventional methods for detecting ethylene include gas chromatographs or optical mid-infrared sensors, which are expensive and, in the case of gas chromatographs, are hardly suitable for automated parallelized online measurement. Electrochemical ethylene sensors are cheap but often suffer from poor resolution, baseline drifting, and target gas oxidation. Thus, measuring ethylene at extremely low levels is challenging.

RESULTS: This report demonstrates the integration of electrochemical ethylene sensors into a respiration activity monitoring system (RAMOS) that measures, in addition to the oxygen transfer rate, the ethylene transfer rate in eight parallel shake flasks. A calibration method is presented that is not prone to baseline drifting and considers target gas oxidation at the sensor. In this way, changes in ethylene transfer rate as low as 4 nmol/L/h can be resolved. In confirmatory experiments, the overall accuracy of the method was similar to that of gas chromatography-mass spectrometry (GC/MS) measurements. The RAMOS-based ethylene determination method was exemplified with parsley suspension-cultured cells that were primed for enhanced defense by pretreatment with salicylic acid, methyl jasmonate or 4-chlorosalicylic acid and challenged with the microbial pattern Pep13. Ethylene release into the headspace of the shake flask was observed upon treatment with salicylic acid and methyl jasmonate was further enhanced, in case of salicylic acid and 4-chlorosalicylic acid, upon Pep13 challenge.

CONCLUSION: A conventional RAMOS device was modified for simultaneous measurement of the ethylene transfer rate in eight parallel shake flasks at nmol/L/h resolution. For the first time electrochemical sensors are used to provide a medium-throughput method for monitoring ethylene release by plants. Currently, this can only be achieved by costly laser-based detection systems and automated gas chromatographs. The new method is particularly suitable for plant cell suspension cultures. However, the method may also be applicable to intact plants, detached leaves or other plant tissues. In addition, the general principle of the technology is likely extendable to other volatiles or gases as well, such as nitric oxide or hydrogen peroxide.}, } @article {pmid29859040, year = {2018}, author = {Wang, Z and Wang, X and Xie, B and Hong, Z and Yang, Q}, title = {Arabidopsis NUCLEOSTEMIN-LIKE 1 (NSN1) regulates cell cycling potentially by cooperating with nucleosome assembly protein AtNAP1;1.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {99}, pmid = {29859040}, issn = {1471-2229}, support = {MCB 0548525//National Science Foundation/ ; ASTIP-IAS14//The Agricultural Science and Technology Innovation Program from China/ ; }, mesh = {Arabidopsis/*genetics/physiology ; Arabidopsis Proteins/genetics/*metabolism ; *Cell Cycle ; Cell Proliferation ; GTP-Binding Proteins/genetics/*metabolism ; Genes, Reporter ; Mutation ; Nucleosome Assembly Protein 1/genetics/*metabolism ; Nucleosomes/*metabolism ; Two-Hybrid System Techniques ; }, abstract = {BACKGROUND: In mammals, nucleostemin (NS), a nucleolar GTPase, is involved in stem cell proliferation, embryogenesis and ribosome biogenesis. Arabidopsis NUCLEOSTEMIN-LIKE 1 (NSN1) has previously been shown to be essential for plant growth and development. However, the role of NSN1 in cell proliferation is largely unknown.

RESULTS: Using nsn1, a loss-of-function mutant of Arabidopsis NSN1, we investigated the function of NSN1 in plant cell proliferation and cell cycle regulation. Morphologically, nsn1 exhibited developmental defects in both leaves and roots, producing severely reduced vegetative organs with a much smaller number of cells than those in the wild type. Dynamic analysis of leaf and root growth revealed a lower cell proliferation rate and slower cell division in nsn1. Consistently, the transcriptional levels of key cell cycle genes, including those regulating the transition of G1-S and G2-M, were reduced drastically in nsn1. The introduction of CYCLIN B1::GUS into nsn1 resulted in confined expression of GUS in both the leaf primordia and root meristem, indicating that cell proliferation was hampered by the mutation of NSN1. Upon subjection to treatment with bleomycin and methyl methanesulfonate (MMS), nsn1 plants exhibited hypersensitivity to the genotoxic agents. In the nucleus, NSN1 interacted with nucleosome assembly protein1 (AtNAP1;1), a highly conserved histone chaperone functioning in cell proliferation. Notably, the N-terminal conserved domains of Arabidopsis NSN1 were critical for the physical interaction.

CONCLUSIONS: As a conserved homolog of mammalian nucleostemin, Arabidopsis NSN1 plays pivotal roles in embryogenesis and ribosome biogenesis. In this study, NSN1 was found to function as a positive regulator in cell cycle progression. The interaction between NSN1 and histone chaperone AtNAP1;1, and the high resemblance in sensitivity to genotoxics between nsn1 and atnap1;1 imply the indispensability of the two nuclear proteins for cell cycle regulation. This work provides an insight into the delicate control of cell proliferation through the cooperation of a GTP-binding protein with a nucleosome assembly/disassembly protein in Arabidopsis.}, } @article {pmid29859037, year = {2018}, author = {de Gérando, HM and Wasels, F and Bisson, A and Clement, B and Bidard, F and Jourdier, E and López-Contreras, AM and Ferreira, NL}, title = {Correction to: Genome and transcriptome of the natural isopropanol producer Clostridium beijerinckii DSM6423.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {423}, pmid = {29859037}, issn = {1471-2164}, abstract = {Following the publication of this article [1], the authors noticed that Figs. 2, 3 and 4 were in the incorrect order and thus had incorrect captions.}, } @article {pmid29859036, year = {2018}, author = {Adamek, M and Alanjary, M and Sales-Ortells, H and Goodfellow, M and Bull, AT and Winkler, A and Wibberg, D and Kalinowski, J and Ziemert, N}, title = {Comparative genomics reveals phylogenetic distribution patterns of secondary metabolites in Amycolatopsis species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {426}, pmid = {29859036}, issn = {1471-2164}, support = {TTU 9.704//Deutsches Zentrum für Infektionsforschung/ ; 031A533//Bielefeld-Gießen Center for Microbial Bioinformatics/ ; Emeritus Fellowship//Leverhulme Trust/ ; }, mesh = {Actinomycetales/*genetics/*metabolism ; Genome, Bacterial/genetics ; *Genomics ; Multigene Family/genetics ; *Phylogeny ; Secondary Metabolism/*genetics ; }, abstract = {BACKGROUND: Genome mining tools have enabled us to predict biosynthetic gene clusters that might encode compounds with valuable functions for industrial and medical applications. With the continuously increasing number of genomes sequenced, we are confronted with an overwhelming number of predicted clusters. In order to guide the effective prioritization of biosynthetic gene clusters towards finding the most promising compounds, knowledge about diversity, phylogenetic relationships and distribution patterns of biosynthetic gene clusters is necessary.

RESULTS: Here, we provide a comprehensive analysis of the model actinobacterial genus Amycolatopsis and its potential for the production of secondary metabolites. A phylogenetic characterization, together with a pan-genome analysis showed that within this highly diverse genus, four major lineages could be distinguished which differed in their potential to produce secondary metabolites. Furthermore, we were able to distinguish gene cluster families whose distribution correlated with phylogeny, indicating that vertical gene transfer plays a major role in the evolution of secondary metabolite gene clusters. Still, the vast majority of the diverse biosynthetic gene clusters were derived from clusters unique to the genus, and also unique in comparison to a database of known compounds. Our study on the locations of biosynthetic gene clusters in the genomes of Amycolatopsis' strains showed that clusters acquired by horizontal gene transfer tend to be incorporated into non-conserved regions of the genome thereby allowing us to distinguish core and hypervariable regions in Amycolatopsis genomes.

CONCLUSIONS: Using a comparative genomics approach, it was possible to determine the potential of the genus Amycolatopsis to produce a huge diversity of secondary metabolites. Furthermore, the analysis demonstrates that horizontal and vertical gene transfer play an important role in the acquisition and maintenance of valuable secondary metabolites. Our results cast light on the interconnections between secondary metabolite gene clusters and provide a way to prioritize biosynthetic pathways in the search and discovery of novel compounds.}, } @article {pmid29859035, year = {2018}, author = {Salilew-Wondim, D and Saeed-Zidane, M and Hoelker, M and Gebremedhn, S and Poirier, M and Pandey, HO and Tholen, E and Neuhoff, C and Held, E and Besenfelder, U and Havlicek, V and Rings, F and Fournier, E and Gagné, D and Sirard, MA and Robert, C and Gad, A and Schellander, K and Tesfaye, D}, title = {Genome-wide DNA methylation patterns of bovine blastocysts derived from in vivo embryos subjected to in vitro culture before, during or after embryonic genome activation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {424}, pmid = {29859035}, issn = {1471-2164}, support = {NA//EmbryoGENE/ ; }, mesh = {Animals ; Blastocyst/*metabolism ; Cattle ; Chromosomes, Mammalian/genetics ; *DNA Methylation ; *Embryo Culture Techniques ; Embryonic Development/*genetics ; *Genomics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Aberrant DNA methylation patterns of genes required for development are common in in vitro produced embryos. In this regard, we previously identified altered DNA methylation patterns of in vivo developed blastocysts from embryos which spent different stages of development in vitro, indicating carryover effects of suboptimal culture conditions on epigenetic signatures of preimplantation embryos. However, epigenetic responses of in vivo originated embryos to suboptimal culture conditions are not fully understood. Therefore, here we investigated DNA methylation patterns of in vivo derived bovine embryos subjected to in vitro culture condition before, during or after major embryonic genome activation (EGA). For this, in vivo produced 2-, 8- and 16-cell stage embryos were cultured in vitro until the blastocyst stage and blastocysts were used for genome-wide DNA methylation analysis.

RESULTS: The 2- and 8-cell flushed embryo groups showed lower blastocyst rates compared to the 16-cell flush group. This was further accompanied by increased numbers of differentially methylated genomic regions (DMRs) in blastocysts of the 2- and 8-cell flush groups compared to the complete in vivo control ones. Moreover, 1623 genomic loci including imprinted genes were hypermethylated in blastocyst of 2-, 8- and 16-cell flushed groups, indicating the presence of genomic regions which are sensitive to the in vitro culture at any stage of embryonic development. Furthermore, hypermethylated genomic loci outnumbered hypomethylated ones in blastocysts of 2- and 16-cell flushed embryo groups, but the opposite occurred in the 8-cell group. Moreover, DMRs which were unique to blastocysts of the 2-cell flushed group and inversely correlated with corresponding mRNA expression levels were involved in plasma membrane lactate transport, amino acid transport and phosphorus metabolic processes, whereas DMRs which were specific to the 8-cell group and inversely correlated with corresponding mRNA expression levels were involved in several biological processes including regulation of fatty acids and steroid biosynthesis processes.

CONCLUSION: In vivo embryos subjected to in vitro culture before and during major embryonic genome activation (EGA) are prone to changes in DNA methylation marks and exposure of in vivo embryos to in vitro culture during the time of EGA increased hypomethylated genomic loci in blastocysts.}, } @article {pmid29858620, year = {2018}, author = {Zhong, C and Zong, G and Qian, S and Liu, M and Fu, J and Zhang, P and Li, J and Cao, G}, title = {Complete Genome Sequence of Actinosynnema pretiosum X47, An Industrial Strain that Produces the Antibiotic Ansamitocin AP-3.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1521-1}, pmid = {29858620}, issn = {1432-0991}, support = {31700065//National Natural Science Foundation of China/ ; ZR2017BC040//Natural Science Foundation of Shandong Province/ ; }, abstract = {Ansamitocins are extraordinarily potent antitumor agents. Ansamitocin P-3 (AP-3), which is produced by Actinosynnema pretiosum, has been developed as a cytotoxic drug for breast cancer. Despite its importance, AP-3 is of limited applicability because of the low production yield. A. pretiosum strain X47 was developed from A. pretiosum ATCC 31565 by mutation breeding and shows a relatively high AP-3 yield. Here, we analyzed the A. pretiosum X47 genome, which is ~8.13 Mb in length with 6693 coding sequences, 58 tRNA genes, and 15 rRNA genes. The DNA sequence of the ansamitocin biosynthetic gene cluster is highly similar to that of the corresponding cluster in A. pretiosum ATCC 31565, with 99.9% identity. However, RT-qPCR analysis showed that the expression levels of ansamitocin biosynthetic genes were significantly increased in X47 compared with the levels in the wild-type strain, consistent with the higher yield of AP-3 in X47. The annotated complete genome sequence of this strain will facilitate understanding the molecular mechanisms of ansamitocin biosynthesis and regulation in A. pretiosum and help further genetic engineering studies to enhance the production of AP-3.}, } @article {pmid29858619, year = {2018}, author = {Togo, AH and Diop, A and Million, M and Maraninchi, M and Lagier, JC and Robert, C and Di Pinto, F and Raoult, D and Fournier, PE and Bittar, F}, title = {Draft Genome and Description of Eisenbergiella massiliensis Strain AT11T: A New Species Isolated from Human Feces After Bariatric Surgery.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1274-1281}, pmid = {29858619}, issn = {1432-0991}, mesh = {Bacterial Typing Techniques ; Bariatric Surgery ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry/metabolism ; Feces/*microbiology ; France ; Gastrointestinal Microbiome ; *Genome, Bacterial ; Genomics ; Humans ; Male ; Middle Aged ; Obesity, Morbid/*microbiology/surgery ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {A novel strain of a Gram-stain negative, non-motile, non-spore forming rod-shaped, obligate anaerobic bacterium, designated AT11T, was isolated from a stool sample of a morbidly obese woman living in Marseille, France. This bacterium was characterized using biochemical, chemotaxonomic, and phylogenetic methods. The 16S rRNA gene sequence analysis showed that strain AT11T had a 97.8% nucleotide sequence similarity with Eisenbergiella tayi strain B086562T, the closest species with standing in nomenclature. The major cellular fatty acids of the novel isolate were C16:0 followed by saturated or unsaturated C18 fatty acids (C18:1n9, C18:1n5 and C18:0). The draft genome of strain AT11T is 7,114,554 bp long with 48% G+C content. 6176 genes were predicted, including 6114 protein-coding genes and 62 were RNAs (with 2 5S rRNA genes, two 16S rRNA genes, two 23S rRNA genes, and 56 tRNA genes). The digital DNA-DNA hybridization (dDDH) relatedness between the new isolate and E. tayi strain B086562T was 23.1% ± 2.2. Based on the phenotypic, chemotaxonomic, genomic, and phylogenetic characteristics, Eisenbergiella massiliensis sp. nov., is proposed. The type strain is AT11T (= DSM 100838T = CSUR P2478T).}, } @article {pmid29858596, year = {2018}, author = {York, A}, title = {On the origin of Plasmodium falciparum.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {393}, doi = {10.1038/s41579-018-0038-8}, pmid = {29858596}, issn = {1740-1534}, } @article {pmid29858585, year = {2018}, author = {Zhao, Q and Feng, Q and Lu, H and Li, Y and Wang, A and Tian, Q and Zhan, Q and Lu, Y and Zhang, L and Huang, T and Wang, Y and Fan, D and Zhao, Y and Wang, Z and Zhou, C and Chen, J and Zhu, C and Li, W and Weng, Q and Xu, Q and Wang, ZX and Wei, X and Han, B and Huang, X}, title = {Publisher Correction: Pan-genome analysis highlights the extent of genomic variation in cultivated and wild rice.}, journal = {Nature genetics}, volume = {50}, number = {8}, pages = {1196}, doi = {10.1038/s41588-018-0136-6}, pmid = {29858585}, issn = {1546-1718}, abstract = {When published, this article did not initially appear open access. This error has been corrected, and the open access status of the paper is noted in all versions of the paper.}, } @article {pmid29858344, year = {2018}, author = {Zou, YQ and Wu, LN and Liu, Q and Luo, XY and Guo, SF and Cao, JH and Tey, MK and You, L}, title = {Beating the classical precision limit with spin-1 Dicke states of more than 10,000 atoms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6381-6385}, pmid = {29858344}, issn = {1091-6490}, abstract = {Interferometry is a paradigm for most precision measurements. Using N uncorrelated particles, the achievable precision for a two-mode (two-path) interferometer is bounded by the standard quantum limit (SQL), [Formula: see text], due to the discrete (quanta) nature of individual measurements. Despite being a challenging benchmark, the two-mode SQL has been approached in a number of systems, including the Laser Interferometer Gravitational-Wave Observatory and today's best atomic clocks. For multimode interferometry, the SQL becomes [Formula: see text] using M modes. Higher precision can also be achieved using entangled particles such that quantum noises from individual particles cancel out. In this work, we demonstrate an interferometric precision of [Formula: see text] dB beyond the three-mode SQL, using balanced spin-1 (three-mode) Dicke states containing thousands of entangled atoms. The input quantum states are deterministically generated by controlled quantum phase transition and exhibit close to ideal quality. Our work shines light on the pursuit of quantum metrology beyond SQL.}, } @article {pmid29858272, year = {2018}, author = {Goodson, HV and Jonasson, EM}, title = {Microtubules and Microtubule-Associated Proteins.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a022608}, pmid = {29858272}, issn = {1943-0264}, abstract = {SUMMARYMicrotubules act as "railways" for motor-driven intracellular transport, interact with accessory proteins to assemble into larger structures such as the mitotic spindle, and provide an organizational framework to the rest of the cell. Key to these functions is the fact that microtubules are "dynamic." As with actin, the polymer dynamics are driven by nucleotide hydrolysis and influenced by a host of specialized regulatory proteins, including microtubule-associated proteins. However, microtubule turnover involves a surprising behavior-termed dynamic instability-in which individual polymers switch stochastically between growth and depolymerization. Dynamic instability allows microtubules to explore intracellular space and remodel in response to intracellular and extracellular cues. Here, we review how such instability is central to the assembly of many microtubule-based structures and to the robust functioning of the microtubule cytoskeleton.}, } @article {pmid29858127, year = {2018}, author = {Starnbach, MN}, title = {Action Needed on Chlamydia Vaccines.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {639-640}, doi = {10.1016/j.tim.2018.05.006}, pmid = {29858127}, issn = {1878-4380}, abstract = {Chlamydia trachomatis is the most common infectious disease in the USA for which the Centers for Disease Control (CDC) collects case reports. Its prevalence in young women is a public health crisis given the threat to their reproductive health. Consequently, development of a vaccine to prevent infection should be prioritized.}, } @article {pmid29858018, year = {2018}, author = {Schulz, JD and Moser, W and Hürlimann, E and Keiser, J}, title = {Preventive Chemotherapy in the Fight against Soil-Transmitted Helminthiasis: Achievements and Limitations.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {590-602}, doi = {10.1016/j.pt.2018.04.008}, pmid = {29858018}, issn = {1471-5007}, mesh = {Animals ; Anthelmintics/pharmacology/*therapeutic use ; Chemoprevention/*standards ; Drug Resistance ; Helminthiasis/*drug therapy/*prevention & control/transmission ; Helminths/drug effects ; Humans ; Soil/*parasitology ; }, abstract = {Soil-transmitted helminths (STHs) are endemic in more than half of the world's countries. The World Health Organization has advocated targeted preventive chemotherapy (PC) to control STH infections by distributing albendazole or mebendazole to at-risk populations. While the overall impact and sustainability of this strategy is disputed, a decrease in moderate and heavy STH infections can be largely attributed to a scale-up of drug distribution. Two factors might jeopardise the success of PC programs. First, the benzimidazoles possess unsatisfactory efficacy against Trichuris trichiura infections. Second, increased drug distributions might trigger anthelmintic resistance. This review presents an overview of the burden of STH infections, the evolution of PC along with its success and challenges, recent estimates of the efficacy of recommended drugs, and alternative treatment options.}, } @article {pmid29857967, year = {2018}, author = {Mounier, A and Correia, M and Rivera, F and Crivellaro, F and Power, R and Jeffery, J and Wilshaw, A and Foley, RA and Mirazón Lahr, M}, title = {Who were the Nataruk people? Mandibular morphology among late Pleistocene and early Holocene fisher-forager populations of West Turkana (Kenya).}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {235-253}, doi = {10.1016/j.jhevol.2018.04.013}, pmid = {29857967}, issn = {1095-8606}, abstract = {Africa is the birthplace of the species Homo sapiens, and Africans today are genetically more diverse than other populations of the world. However, the processes that underpinned the evolution of African populations remain largely obscure. Only a handful of late Pleistocene African fossils (∼50-12 Ka) are known, while the more numerous sites with human fossils of early Holocene age are patchily distributed. In particular, late Pleistocene and early Holocene human diversity in Eastern Africa remains little studied, precluding any analysis of the potential factors that shaped human diversity in the region, and more broadly throughout the continent. These periods include the Last Glacial Maximum (LGM), a moment of extreme aridity in Africa that caused the fragmentation of population ranges and localised extinctions, as well as the 'African Humid Period', a moment of abrupt climate change and enhanced connectivity throughout Africa. East Africa, with its range of environments, may have acted as a refugium during the LGM, and may have played a critical biogeographic role during the heterogene`ous environmental recovery that followed. This environmental context raises a number of questions about the relationships among early Holocene African populations, and about the role played by East Africa in shaping late hunter-gatherer biological diversity. Here, we describe eight mandibles from Nataruk, an early Holocene site (∼10 Ka) in West Turkana, offering the opportunity of exploring population diversity in Africa at the height of the 'African Humid Period'. We use 3D geometric morphometric techniques to analyze the phenotypic variation of a large mandibular sample. Our results show that (i) the Nataruk mandibles are most similar to other African hunter-fisher-gatherer populations, especially to the fossils from Lothagam, another West Turkana locality, and to other early Holocene fossils from the Central Rift Valley (Kenya); and (ii) a phylogenetic connection may have existed between these Eastern African populations and some Nile Valley and Maghrebian groups, who lived at a time when a Green Sahara may have allowed substantial contact, and potential gene flow, across a vast expanse of Northern and Eastern Africa.}, } @article {pmid29857804, year = {2018}, author = {Wray, KB}, title = {A new twist to the No Miracles Argument for the success of science.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {86-89}, doi = {10.1016/j.shpsa.2018.02.002}, pmid = {29857804}, issn = {0039-3681}, abstract = {J. D. Trout has recently developed a new defense of scientific realism, a new version of the No Miracles Argument. I critically evaluate Trout's novel defense of realism. I argue that Trout's argument for scientific realism and the related explanation for the success of science are self-defeating. In the process of arguing against the traditional realist strategies for explaining the success of science, he inadvertently undermines his own argument.}, } @article {pmid29857803, year = {2018}, author = {Curry, DS}, title = {Cartesian critters can't remember.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {72-85}, doi = {10.1016/j.shpsa.2018.03.001}, pmid = {29857803}, issn = {0039-3681}, abstract = {Descartes held the following view of declarative memory: to remember is to reconstruct an idea that you intellectually recognize as a reconstruction. Descartes countenanced two overarching varieties of declarative memory. To have an intellectual memory is to intellectually reconstruct a universal idea that you recognize as a reconstruction, and to have a sensory memory is to neurophysiologically reconstruct a particular idea that you recognize as a reconstruction. Sensory remembering is thus a capacity of neither ghosts nor machines, but only of human beings qua mind-body unions. This interpretation unifies Descartes's various remarks (and conspicuous silences) about remembering, from the 1628 Rules for the Direction of the Mind through the suppressed-in-1633 Treatise of Man to the 1649 Passions of the Soul. It also rebuts a prevailing thesis in the current secondary literature-that Cartesian critters can remember-while incorporating the textual evidence for that thesis-Descartes's detailed descriptions of the corporeal mechanisms that construct sensory memories.}, } @article {pmid29857802, year = {2018}, author = {Menke, C}, title = {The Whewell-Mill debate on predictions, from Mill's point of view.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {60-71}, doi = {10.1016/j.shpsa.2018.02.007}, pmid = {29857802}, issn = {0039-3681}, abstract = {John Stuart Mill, in his debate with William Whewell on the nature and logic of induction, is regarded as being the first to dismiss the supposed value of successful predictions as merely psychological. I shall argue that this view of the Whewell-Mill debate on predictions misconstrues Mill's position and argument. From Mill's point of view, the controversial point was not the question whether predictions 'count more' than ex-post explanations but the alleged assertion by Whewell that the successful predictions of the wave theory of light prove the existence of the ether. Mill argued that, on the one hand, the predictions of the wave theory of light do not and cannot provide evidence for the existence of the ether; as evidence for the laws of the theory, on the other hand, the predictions are superfluous, the laws being already well-confirmed. Mill actually endorsed a requirement of independent support closely resembling Whewell's requirements for hypotheses; the controversy on the value of predictions is a product of the 20th century.}, } @article {pmid29857801, year = {2018}, author = {Gundersen, T}, title = {Scientists as experts: A distinct role?.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {52-59}, doi = {10.1016/j.shpsa.2018.02.006}, pmid = {29857801}, issn = {0039-3681}, abstract = {The role of scientists as experts is crucial to public policymaking. However, the expert role is contested and unsettled in both public and scholarly discourse. In this paper, I provide a systematic account of the role of scientists as experts in policymaking by examining whether there are any normatively relevant differences between this role and the role of scientists as researchers. Two different interpretations can be given of how the two roles relate to each other. The separability view states that there is a normatively relevant difference between the two roles, whereas the inseparability view denies that there is such a difference. Based on a systematic analysis of the central aspects of the role of scientists as experts - that is, its aim, context, mode of output, and standards, I propose a moderate version of the separability view. Whereas the aim of scientific research is typically to produce new knowledge through the use of scientific method for evaluation and dissemination in internal settings, the aim of the expert is to provide policymakers and the public with relevant and applicable knowledge that can premise political reasoning and deliberation.}, } @article {pmid29857800, year = {2018}, author = {Barwich, AS}, title = {How to be rational about empirical success in ongoing science: The case of the quantum nose and its critics.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {40-51}, doi = {10.1016/j.shpsa.2018.02.005}, pmid = {29857800}, issn = {0039-3681}, abstract = {Empirical success is a central criterion for scientific decision-making. Yet its understanding in philosophical studies of science deserves renewed attention: Should philosophers think differently about the advancement of science when they deal with the uncertainty of outcome in ongoing research in comparison with historical episodes? This paper argues that normative appeals to empirical success in the evaluation of competing scientific explanations can result in unreliable conclusions, especially when we are looking at the changeability of direction in unsettled investigations. The challenges we encounter arise from the inherent dynamics of disciplinary and experimental objectives in research practice. In this paper we discuss how these dynamics inform the evaluation of empirical success by analyzing three of its requirements: data accommodation, instrumental reliability, and predictive power. We conclude that the assessment of empirical success in developing inquiry is set against the background of a model's interactive success and prospective value in an experimental context. Our argument is exemplified by the analysis of an apparent controversy surrounding the model of a quantum nose in research on olfaction. Notably, the public narrative of this controversy rests on a distorted perspective on measures of empirical success.}, } @article {pmid29857799, year = {2018}, author = {Dion, SM}, title = {Natural classification and Pierre Duhem's historical work: Which relationships?.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {34-39}, doi = {10.1016/j.shpsa.2018.02.001}, pmid = {29857799}, issn = {0039-3681}, } @article {pmid29857798, year = {2018}, author = {Fisher, AA}, title = {Inductive reasoning in the context of discovery: Analogy as an experimental stratagem in the history and philosophy of science.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {23-33}, doi = {10.1016/j.shpsa.2018.01.008}, pmid = {29857798}, issn = {0039-3681}, abstract = {Building on Norton's "material theory of induction," this paper shows through careful historical analysis that analogy can act as a methodological principle or stratagem, providing experimentalists with a useful framework to assess data and devise novel experiments. Although this particular case study focuses on late eighteenth and early nineteenth-century experiments on the properties and composition of acids, the results of this investigation may be extended and applied to other research programs. A stage in-between what Steinle calls "exploratory experimentation" and robust theory, I argue that analogy encouraged research to substantiate why the likenesses should outweigh the differences (or vice versa) when evaluating results and designing experiments.}, } @article {pmid29857797, year = {2018}, author = {Schmid, J}, title = {Schelling's method of Darstellung: Presenting nature through experiment.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {12-22}, doi = {10.1016/j.shpsa.2018.01.009}, pmid = {29857797}, issn = {0039-3681}, } @article {pmid29857796, year = {2018}, author = {Reichenberger, A}, title = {Émilie Du Châtelet's interpretation of the laws of motion in the light of 18th century mechanics.}, journal = {Studies in history and philosophy of science}, volume = {69}, number = {}, pages = {1-11}, doi = {10.1016/j.shpsa.2018.01.006}, pmid = {29857796}, issn = {0039-3681}, abstract = {Émilie Du Châtelet is well known for her French translation of Newton's Philosophiae Naturalis Principia Mathematica. It is the first and only French translation of Newton's magnum opus. The complete work appeared in 1759 under the title Principes mathématiques de la philosophie naturelle, par feue Madame la Marquise Du Chastellet. Before translating Newton's Principia, Du Châtelet worked on her Institutions de physique. In this book she defended the Leibnizian concept of living forces - vis viva. This paper argues that both of these works were part of a critical transformation and consolidation of post-Newtonian mechanics in the early 18th century, beyond Newton and Leibniz. This will be shown by comparing Du Châtelet's translation of Newton's axioms with her own formulations of the laws of motion in light of Thomas Le Seur's and François Jacquier's Geneva edition which holds a special place among the several editions of the Principia that appeared in the early 18th century.}, } @article {pmid29857034, year = {2018}, author = {Cabezas, CE and Briones, AC and Aguirre, C and Pardo-Esté, C and Castro-Severyn, J and Salinas, CR and Baquedano, MS and Hidalgo, AA and Fuentes, JA and Morales, EH and Meneses, CA and Castro-Nallar, E and Saavedra, CP}, title = {The transcription factor SlyA from Salmonella Typhimurium regulates genes in response to hydrogen peroxide and sodium hypochlorite.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {263-278}, doi = {10.1016/j.resmic.2018.04.003}, pmid = {29857034}, issn = {1769-7123}, mesh = {Animals ; Bacterial Proteins/*genetics ; Cell Line ; Dicarboxylic Acid Transporters/genetics ; Gene Expression Profiling ; Hydrogen Peroxide/*pharmacology ; Mice ; Oxidants/*pharmacology ; Phosphofructokinase-1/genetics ; Promoter Regions, Genetic/genetics ; RAW 264.7 Cells ; Salmonella Infections/microbiology/*pathology ; Salmonella typhimurium/*genetics/metabolism/*pathogenicity ; Sodium Hypochlorite/*pharmacology ; Trans-Activators/genetics ; Transcription Factors/*genetics ; Virulence/genetics ; }, abstract = {Salmonella Typhimurium is an intracellular pathogen that is capable of generating systemic fever in a murine model. Over the course of the infection, Salmonella faces different kinds of stressors, including harmful reactive oxygen species (ROS). Various defence mechanisms enable Salmonella to successfully complete the infective process in the presence of such stressors. The transcriptional factor SlyA is involved in the oxidative stress response and invasion of murine macrophages. We evaluated the role of SlyA in response to H2O2 and NaOCl and found an increase of slyA expression upon exposure to these toxics. However, the SlyA target genes and the molecular mechanisms by which they influence the infective process are unknown. We hypothesised that SlyA regulates the expression of genes required for ROS resistance, metabolism, or virulence under oxidative stress conditions. Transcriptional profiling in wild type and ΔslyA strains confirmed that SlyA regulates the expression of several genes involved in virulence [sopD (STM14_3550), sopE2 (STM14_2244), hilA (STM14_3475)] and central metabolism [kgtP (STM14_3252), fruK (STM14_2722), glpA (STM14_2819)] in response to H2O2 and NaOCl. These findings were corroborated by functional assay and transcriptional fusion assays using GFP. DNA-protein interaction assays showed that SlyA regulates these genes through direct interaction with their promoter regions.}, } @article {pmid29856930, year = {2018}, author = {Lang, KS and Merrikh, H}, title = {The Clash of Macromolecular Titans: Replication-Transcription Conflicts in Bacteria.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {71-88}, pmid = {29856930}, issn = {1545-3251}, support = {DP2 GM110773/GM/NIGMS NIH HHS/United States ; T32 AI055396/AI/NIAID NIH HHS/United States ; }, abstract = {Within the last decade, it has become clear that DNA replication and transcription are routinely in conflict with each other in growing cells. Much of the seminal work on this topic has been carried out in bacteria, specifically, Escherichia coli and Bacillus subtilis; therefore, studies of conflicts in these species deserve special attention. Collectively, the recent findings on conflicts have fundamentally changed the way we think about DNA replication in vivo. Furthermore, new insights on this topic have revealed that the conflicts between replication and transcription significantly influence many key parameters of cellular function, including genome organization, mutagenesis, and evolution of stress response and virulence genes. In this review, we discuss the consequences of replication-transcription conflicts on the life of bacteria and describe some key strategies cells use to resolve them. We put special emphasis on two critical aspects of these encounters: (a) the consequences of conflicts on replisome stability and dynamics, and (b) the resulting increase in spontaneous mutagenesis.}, } @article {pmid29856310, year = {2018}, author = {Liang, QY and Xu, ZX and Zhang, J and Chen, GJ and Du, ZJ}, title = {Salegentibacter sediminis sp. nov., a marine bacterium of the family Flavobacteriaceae isolated from coastal sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2375-2380}, doi = {10.1099/ijsem.0.002849}, pmid = {29856310}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile, rod-shaped (0.2-0.3×0.8-1.4 µm) and yellow-pigmented bacterium, designated K5023T, was isolated from marine sediment obtained off the coast of Weihai, China. Strain K5023T was found to grow at 16-37 °C (optimum, 33 °C), at pH 6.5-8.0 (optimum, 7.0-7.5) and in the presence of 1-10 % (w/v) NaCl (optimum, 5 %). Cells were oxidase-positive and catalase-negative. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain K5023T is a member of the genus Salegentibacter and exhibited the hightest sequence similarity to Salegentibacter flavus DSM 22702T (97.0 %). Menaquinone-6 (MK-6) was detected as the major respiratory quinone. The dominant cellular fatty acids were iso-C15 : 0 and anteiso-C15 : 0. The DNA G+C content of strain K5023T was 40.1 mol%. The polar lipids included one phosphatidylethanolamine, three phospholipids and four unidentified lipids. Based on the phylogenetic and phenotypic characteristics, strain K5023T is considered to represent a novel species of the genus Salegentibacter, for which the name Salegentibacter sediminis sp. nov. is proposed. The type strain is K5023T (=KCTC 52477T=MCCC 1H00173T).}, } @article {pmid29856112, year = {2018}, author = {Timmis, K and Timmis, J}, title = {Environmental Microbiology is 20!.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14131}, pmid = {29856112}, issn = {1462-2920}, } @article {pmid29855703, year = {2018}, author = {Thümecke, S and Schröder, R}, title = {UTR-specific knockdown of Distal-less and Sp8 leads to new phenotypic variants in the flour beetle Tribolium.}, journal = {Development genes and evolution}, volume = {228}, number = {3-4}, pages = {163-170}, pmid = {29855703}, issn = {1432-041X}, support = {BE 4850/1-1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {*3' Untranslated Regions ; Animals ; Homeodomain Proteins/*antagonists & inhibitors/genetics ; Insect Proteins/*antagonists & inhibitors/genetics ; Phenotype ; RNA Interference ; RNA, Double-Stranded ; Transcription Factors/*antagonists & inhibitors/genetics ; Tribolium/*genetics/physiology ; }, abstract = {RNA interference (RNAi)-mediated knockdown serves as an effective technique for the functional analysis of developmental genes that is well established in many organisms. In the beetle Tribolium castaneum, double-stranded RNA is applied by simple injection and distributes systemically within the tissue. Thus, systematic testing for RNAi specificity and efficiency is easily possible in this organism. Generally, the use of non-overlapping dsRNA fragments yielding qualitatively identical phenotypes is the method of choice to verify target-specific knockdown effects. Here, we show that UTR-specific RNAi results in different effects regarding quality, severity and penetrance when compared to RNAi fragments directed at the coding region. Furthermore, when using 3'UTR-specific dsRNA, we first describe the Distal-lessRNAi antenna-to-leg transformation phenotype in the Tribolium larva, which has only been observed in the adult beetle and Drosophila so far. In addition, we unexpectedly observed sterility effects caused by 3'UTR-specific knockdown of the Tribolium-Sp8 orthologue that is not seen when dsRNA targeted a sequence within the coding-region or the 5'UTR that itself led to early embryonic lethality. We conclude that targeting UTR sequences by region-specific RNAi can reveal unexpected new aspects of gene function applicable in basic research and crop protection.}, } @article {pmid29855654, year = {2018}, author = {Ricci, M and Peona, V and Guichard, E and Taccioli, C and Boattini, A}, title = {Transposable Elements Activity is Positively Related to Rate of Speciation in Mammals.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {303-310}, pmid = {29855654}, issn = {1432-1432}, abstract = {Transposable elements (TEs) play an essential role in shaping eukaryotic genomes and generating variability. Speciation and TE activity bursts could be strongly related in mammals, in which simple gradualistic models of differentiation do not account for the currently observed species variability. In order to test this hypothesis, we designed two parameters: the Density of insertion (DI) and the Relative rate of speciation (RRS). DI is the ratio between the number of TE insertions in a genome and its size, whereas the RRS is a conditional parameter designed to identify potential speciation bursts. Thus, by analyzing TE insertions in mammals, we defined the genomes as "hot" (high DI) and "cold" (low DI). Then, comparing TE activity among 29 taxonomical families of the whole Mammalia class, 16 intra-order pairs of mammalian species, and four superorders of Eutheria, we showed that taxa with high rates of speciation are associated with "hot" genomes, whereas taxa with low ones are associated with "cold" genomes. These results suggest a remarkable correlation between TE activity and speciation, also being consistent with patterns describing variable rates of differentiation and accounting for the different time frames of the speciation bursts.}, } @article {pmid29855597, year = {2018}, author = {Pilla, G and Tang, CM}, title = {Going around in circles: virulence plasmids in enteric pathogens.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {8}, pages = {484-495}, doi = {10.1038/s41579-018-0031-2}, pmid = {29855597}, issn = {1740-1534}, abstract = {Plasmids have a major role in the development of disease caused by enteric bacterial pathogens. Virulence plasmids are usually large (>40 kb) low copy elements and encode genes that promote host-pathogen interactions. Although virulence plasmids provide advantages to bacteria in specific conditions, they often impose fitness costs on their host. In this Review, we discuss virulence plasmids in Enterobacteriaceae that are important causes of diarrhoea in humans, Shigella spp., Salmonella spp., Yersinia spp and pathovars of Escherichia coli. We contrast these plasmids with those that are routinely used in the laboratory and outline the mechanisms by which virulence plasmids are maintained in bacterial populations. We highlight examples of virulence plasmids that encode multiple mechanisms for their maintenance (for example, toxin-antitoxin and partitioning systems) and speculate on how these might contribute to their propagation and success.}, } @article {pmid29855407, year = {2018}, author = {Dai, YM and Zhang, LL and Li, Y and Li, YQ and Deng, XH and Wang, TT and Yang, F and Tian, YQ and Li, N and Zhou, XM and Liu, XF and Li, WJ}, title = {Corrigendum: Characterization of Trichococcus paludicola sp. nov. and Trichococcus alkaliphilus sp. nov., isolated from a high-elevation wetland, by phenotypic and genomic analyses.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2115}, doi = {10.1099/ijsem.0.002802}, pmid = {29855407}, issn = {1466-5034}, } @article {pmid29855406, year = {2018}, author = {López-Hermoso, C and de la Haba, RR and Sánchez-Porro, C and Ventosa, A}, title = {Corrigendum: Emended description of Salinivibrio proteolyticus, including Salinivibrio costicola subsp. vallismortis and five new isolates.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2124}, doi = {10.1099/ijsem.0.002813}, pmid = {29855406}, issn = {1466-5034}, } @article {pmid29855405, year = {2018}, author = {Kim, YO and Park, IS and Park, S and Nam, BH and Kim, DG and Won, SM and Yoon, JH}, title = {Corrigendum: Paracoccus alimentarius sp. nov., isolated from a Korean foodstuff, salted pollack.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2113}, doi = {10.1099/ijsem.0.002789}, pmid = {29855405}, issn = {1466-5034}, } @article {pmid29855404, year = {2018}, author = {Cole, JK and Morton, BR and Cardamone, HC and Lake, HRR and Dohnalkova, AC and Kim, YM and Kyle, JE and Maezato, Y and Dana, KL and Metz, TO and Romine, MF and Nelson, WC and Lindemann, SR}, title = {Corrigendum: Saliniramus fredricksonii gen. nov., sp. nov., a heterotrophic halophile isolated from Hot Lake, Washington, a member of a novel lineage (Salinarimonadaceae fam. nov.) within the order Rhizobiales, and reclassification of the genus Salinarimonas Liu et al. 2010 into Salinarimonadaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2116-2123}, doi = {10.1099/ijsem.0.002807}, pmid = {29855404}, issn = {1466-5034}, abstract = {There was an error in the proposed genus name in the published article, in that the genus 'Salinivirga' was effectively published while this article was in review. Therefore, the genus 'Salinivirga' should be replaced with 'Saliniramus'. For the convenience of future readers, we have included the complete corrected article below, in which all occurrences of the incorrect genus name have been amended: A halophilic bacterial strain, HL-109T, was isolated from the unicyanobacterial consortium UCC-O, which was obtained from the photosynthetic mat of Hot Lake (Washington, USA). A polyphasic approach using phenotypic, genotypic and chemotaxonomic data was used to classify the strain within the order Rhizobiales. The organism stained Gram-negative and was a moderate thermophile with a growth optimum of 45 °C. It was obligately aerobic, heterotrophic and halophilic, growing in both NaCl and MgSO4 brines. The novel isolate had a polymorphic cellular morphology of short rods with occasional branching, and cells were monotrichous. The major fatty acids detected were C18 : 1, C18 : 0, C16 : 0 and C18 : cyc. Phylogenetic analysis of the 16S rRNA gene placed the strain in the order Rhizobiales and it shared 94 % identity with the type strain of its nearest relative, Salinarimonas ramus. Morphological, chemotaxonomic and phylogenetic results did not affiliate the novel organism with any of the families in the Rhizobiales; therefore, HL-109T is representative of a new lineage, for which the name Saliniramus fredricksonii gen. nov., sp. nov. is proposed, with the type strain HL-109T (=JCM 31876T=DSM 102886T). In addition, examination of the phylogenetics of strain HL-109T and its nearest relatives, Salinarimonas ramus and Salinarimonasrosea, demonstrates that these halophiles form a clade distinct from the described families of the Rhizobiales. We further propose the establishment of a new family, Salinarimonadaceae fam. nov., to accommodate the genera Saliniramus and Salinarimonas (the type genus of the family).}, } @article {pmid29855403, year = {2018}, author = {Kim, YO and Park, IS and Park, S and Nam, BH and Kim, DG and Choi, SG and Bae, JW and Yoon, JH}, title = {Corrigendum: Bizionia berychis sp. nov., isolated from intestinal tract of a splendid alfonsino (Beryx splendens).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2114}, doi = {10.1099/ijsem.0.002790}, pmid = {29855403}, issn = {1466-5034}, } @article {pmid29855402, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 3, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1823-1824}, doi = {10.1099/ijsem.0.002699}, pmid = {29855402}, issn = {1466-5034}, } @article {pmid29855387, year = {2018}, author = {Li, Y and Shi, W and Wasserman, WW}, title = {Genome-wide prediction of cis-regulatory regions using supervised deep learning methods.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {202}, pmid = {29855387}, issn = {1471-2105}, support = {R01 GM084875/GM/NIGMS NIH HHS/United States ; MOP-82875//CIHR/Canada ; }, abstract = {BACKGROUND: In the human genome, 98% of DNA sequences are non-protein-coding regions that were previously disregarded as junk DNA. In fact, non-coding regions host a variety of cis-regulatory regions which precisely control the expression of genes. Thus, Identifying active cis-regulatory regions in the human genome is critical for understanding gene regulation and assessing the impact of genetic variation on phenotype. The developments of high-throughput sequencing and machine learning technologies make it possible to predict cis-regulatory regions genome wide.

RESULTS: Based on rich data resources such as the Encyclopedia of DNA Elements (ENCODE) and the Functional Annotation of the Mammalian Genome (FANTOM) projects, we introduce DECRES based on supervised deep learning approaches for the identification of enhancer and promoter regions in the human genome. Due to their ability to discover patterns in large and complex data, the introduction of deep learning methods enables a significant advance in our knowledge of the genomic locations of cis-regulatory regions. Using models for well-characterized cell lines, we identify key experimental features that contribute to the predictive performance. Applying DECRES, we delineate locations of 300,000 candidate enhancers genome wide (6.8% of the genome, of which 40,000 are supported by bidirectional transcription data), and 26,000 candidate promoters (0.6% of the genome).

CONCLUSION: The predicted annotations of cis-regulatory regions will provide broad utility for genome interpretation from functional genomics to clinical applications. The DECRES model demonstrates potentials of deep learning technologies when combined with high-throughput sequencing data, and inspires the development of other advanced neural network models for further improvement of genome annotations.}, } @article {pmid29855367, year = {2018}, author = {Zheng, W and Rus, F and Hernandez, A and Kang, P and Goldman, W and Silverman, N and Tatar, M}, title = {Dehydration triggers ecdysone-mediated recognition-protein priming and elevated anti-bacterial immune responses in Drosophila Malpighian tubule renal cells.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {60}, pmid = {29855367}, issn = {1741-7007}, support = {R37 AG024360/AG/NIA NIH HHS/United States ; P01 AG033561/AG/NIA NIH HHS/United States ; R01 AI099708/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Drosophila is a powerful model for the study of factors modulating innate immunity. This study examines the effect of water-loss dehydration on innate immune responsiveness in the Drosophila renal system (Malpighian tubules; MTs), and how this leads to elevated host defense and contributes to immunosenescence.

RESULTS: A short period of desiccation-elevated peptidoglycan recognition protein-LC (PGRP-LC) expression in MTs, increased antimicrobial peptide (AMP) gene induction, and protected animals from bacterial infection. We show that desiccation increased ecdysone synthesis in MTs, while inhibition of ecdysone synthesis or ecdysone receptor expression, specifically within MTs, prevented induction of PGRP-LC and reduced protection from bacterial infection. Additionally, aged flies are constitutively water-stressed and have elevated levels of ecdysone and PGRP-LC. Conversely, adults aged at high relative humidity show less water loss and have reduced expression of PGRP-LC and AMPs.

CONCLUSIONS: The Drosophila renal system is an important contributor to host defense and can modulate immune responses in an organ autonomous manner, responding to environmental changes such as desiccation. Desiccation primes immune responsiveness by elevating PGRP-LC expression specifically in MTs. In response to desiccation, ecdysone is produced in MTs and acts in a paracrine fashion to increase PGRP-LC expression, immune responsiveness, and improve host defense. This activity of the renal system may contribute to the immunosenescence observed in Drosophila.}, } @article {pmid29855351, year = {2018}, author = {Zhang, Z and Li, D}, title = {Thermal processing of food reduces gut microbiota diversity of the host and triggers adaptation of the microbiota: evidence from two vertebrates.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {99}, pmid = {29855351}, issn = {2049-2618}, mesh = {Animals ; Bacteroidetes/genetics/*isolation & purification ; Biodiversity ; Catfishes/microbiology ; Diet ; Firmicutes/genetics/*isolation & purification ; Food ; *Food Handling ; Food Microbiology ; Fusobacteria/genetics/*isolation & purification ; Gastrointestinal Microbiome/*genetics ; Hot Temperature ; Male ; Mice ; Mice, Inbred C57BL ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Adoption of thermal processing of the diet drives human evolution and gut microbiota diversity changes in a dietary habit-dependent manner. However, whether thermal processing of food triggers gut microbial variation remains unknown. Herein, we compared the microbiota of non-thermally processed and thermally processed food (NF and TF) and investigated gut microbiota associated with NF and TF in catfish Silurus meridionalis and C57BL/6 mice to assess effects of thermal processing of food on gut microbiota and to further identify the differences in host responses.

RESULTS: We found no differences in overall microbial composition and structure in the pairwise NF and TF, but identified differential microbial communities between food and gut. Both fish and mice fed TF had significantly lower gut microbial diversity than those fed NF. Moreover, thermal processing of food triggered the changes in their microbial communities. Comparative host studies further indicated host species determined gut microbial assemblies, even if fed with the same food. Fusobacteria was the most abundant phylum in the fish, and Bacteroidetes and Firmicutes dominated in the mice. Besides the consistent reduction of Bacteroidetes and the balanced Protebacteria, the response of other dominated gut microbiota in the fish and mice to TF was taxonomically opposite at the phylum level, and those further found at the genus level.

CONCLUSIONS: Our results reveal that thermal processing of food strongly contributes to the reduction of gut microbial diversity and differentially drives microbial alterations in a host-dependent manner, suggesting specific adaptations of host-gut microbiota in vertebrates responding to thermal processing of food. These findings open a window of opportunity to understand the decline in gut microbial diversity and the community variation in human evolution and provide new insights into the host-specific microbial assemblages associated with the use of processing techniques in food preparation in humans and domesticated animals.}, } @article {pmid29855347, year = {2018}, author = {Starr, JR and Huang, Y and Lee, KH and Murphy, CM and Moscicki, AB and Shiboski, CH and Ryder, MI and Yao, TJ and Faller, LL and Van Dyke, RB and Paster, BJ and , }, title = {Oral microbiota in youth with perinatally acquired HIV infection.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {100}, pmid = {29855347}, issn = {2049-2618}, support = {U01 HD052102/HD/NICHD NIH HHS/United States ; U01 HD052104/HD/NICHD NIH HHS/United States ; HD052104/NH/NIH HHS/United States ; HD052102/NH/NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Bacteria/*classification/genetics/*isolation & purification ; Child ; Cross-Sectional Studies ; Dental Caries/*microbiology ; Female ; HIV Infections/*pathology ; Humans ; Longitudinal Studies ; Male ; Microbiota ; Mouth Mucosa/*microbiology ; Periodontitis/*microbiology ; RNA, Ribosomal, 16S/genetics ; Saliva/*microbiology ; Young Adult ; }, abstract = {BACKGROUND: Microbially mediated oral diseases can signal underlying HIV/AIDS progression in HIV-infected adults. The role of the oral microbiota in HIV-infected youth is not known. The Adolescent Master Protocol of the Pediatric HIV/AIDS Cohort Study is a longitudinal study of perinatally HIV-infected (PHIV) and HIV-exposed, uninfected (PHEU) youth. We compared oral microbiome levels and associations with caries or periodontitis in 154 PHIV and 100 PHEU youth.

RESULTS: Species richness and alpha diversity differed little between PHIV and PHEU youth. Group differences in average counts met the significance threshold for six taxa; two Corynebacterium species were lower in PHIV and met thresholds for noteworthiness. Several known periodontitis-associated organisms (Prevotella nigrescens, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Filifactor alocis) exhibited expected associations with periodontitis in PHEU youth, associations not observed in PHIV youth. In both groups, odds of caries increased with counts of taxa in four genera, Streptococcus, Scardovia, Bifidobacterium, and Lactobacillus.

CONCLUSIONS: The microbiomes of PHIV and PHEU youth were similar, although PHIV youth seemed to have fewer "health"-associated taxa such as Corynebacterium species. These results are consistent with the hypothesis that HIV infection, or its treatment, may contribute to oral dysbiosis.}, } @article {pmid29855335, year = {2018}, author = {Younge, NE and Araújo-Pérez, F and Brandon, D and Seed, PC}, title = {Early-life skin microbiota in hospitalized preterm and full-term infants.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {98}, pmid = {29855335}, issn = {2049-2618}, support = {K12 HD043494/HD/NICHD NIH HHS/United States ; R01 GM108494/GM/NIGMS NIH HHS/United States ; K12 HD043494-14//Eunice Kennedy Shriver National Institute of Child Health and Human Development/International ; R01GM108494/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*classification/genetics/*isolation & purification ; Cross-Sectional Studies ; DNA, Bacterial/genetics ; Female ; Humans ; Infant ; Infant, Newborn ; *Infant, Premature ; Male ; Microbiota/genetics ; Skin/*microbiology ; }, abstract = {BACKGROUND: The infant skin microbiota may serve as a reservoir of bacteria that contribute to neonatal infections and stimulate local and systemic immune development. The objectives of our study were to characterize the skin microbiota of preterm and full-term infants during their birth hospitalization and describe its relationship to the microbiota of other body sites and the hospital environment.

RESULTS: We conducted a cross-sectional study of 129 infants, including 40 preterm and 89 full-term infants. Samples were collected from five sites: the forehead and posterior auricular scalp (skin upper body); the periumbilical region, inguinal folds, and upper thighs (skin lower body); the oral cavity; the infant's immediate environment; and stool. Staphylococcus, Streptococcus, Enterococcus, and enteric Gram-negative bacteria including Escherichia and Enterobacter dominated the skin microbiota. The preterm infant microbiota at multiple sites had lower alpha diversity and greater enrichment with Staphylococcus and Escherichia than the microbiota of comparable sites in full-term infants. The community structure was highly variable among individuals but differed significantly by body site, postnatal age, and gestational age. Source tracking indicated that each body site both contributed to and received microbiota from other body sites and the hospital environment.

CONCLUSION: The skin microbiota of preterm and full-term infants varied across individuals, by body site, and by the infant's developmental stage. The skin harbored many organisms that are common pathogens in hospitalized infants. Bacterial source tracking suggests that microbiota are commonly exchanged across body sites and the hospital environment as microbial communities mature in infancy.}, } @article {pmid29855322, year = {2018}, author = {De Beukelaer, H and Davenport, GF and Fack, V}, title = {Core Hunter 3: flexible core subset selection.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {203}, pmid = {29855322}, issn = {1471-2105}, abstract = {BACKGROUND: Core collections provide genebank curators and plant breeders a way to reduce size of their collections and populations, while minimizing impact on genetic diversity and allele frequency. Many methods have been proposed to generate core collections, often using distance metrics to quantify the similarity of two accessions, based on genetic marker data or phenotypic traits. Core Hunter is a multi-purpose core subset selection tool that uses local search algorithms to generate subsets relying on one or more metrics, including several distance metrics and allelic richness.

RESULTS: In version 3 of Core Hunter (CH3) we have incorporated two new, improved methods for summarizing distances to quantify diversity or representativeness of the core collection. A comparison of CH3 and Core Hunter 2 (CH2) showed that these new metrics can be effectively optimized with less complex algorithms, as compared to those used in CH2. CH3 is more effective at maximizing the improved diversity metric than CH2, still ensures a high average and minimum distance, and is faster for large datasets. Using CH3, a simple stochastic hill-climber is able to find highly diverse core collections, and the more advanced parallel tempering algorithm further increases the quality of the core and further reduces variability across independent samples. We also evaluate the ability of CH3 to simultaneously maximize diversity, and either representativeness or allelic richness, and compare the results with those of the GDOpt and SimEli methods. CH3 can sample equally representative cores as GDOpt, which was specifically designed for this purpose, and is able to construct cores that are simultaneously more diverse, and either are more representative or have higher allelic richness, than those obtained by SimEli.

CONCLUSIONS: In version 3, Core Hunter has been updated to include two new core subset selection metrics that construct cores for representativeness or diversity, with improved performance. It combines and outperforms the strengths of other methods, as it (simultaneously) optimizes a variety of metrics. In addition, CH3 is an improvement over CH2, with the option to use genetic marker data or phenotypic traits, or both, and improved speed. Core Hunter 3 is freely available on http://www.corehunter.org .}, } @article {pmid29855268, year = {2018}, author = {Li, T and Wen, J and Zhang, Y and Correll, J and Wang, L and Pan, Q}, title = {Reconstruction of an SSR-based Magnaporthe oryzae physical map to locate avirulence gene AvrPi12.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {47}, pmid = {29855268}, issn = {1471-2180}, abstract = {BACKGROUND: Pathogen avirulence (Avr) genes can evolve rapidly when challenged by the widespread deployment of host genes for resistance. They can be effectively isolated by positional cloning provided a robust and well-populated genetic map is available.

RESULTS: An updated, SSR-based physical map of the rice blast pathogen Magnaporthe oryzae (Mo) has been constructed based on 116 of the 120 SSRs used to assemble the last map, along with 18 newly developed ones. A comparison between the two versions of the map has revealed an altered marker content and order within most of the Mo chromosomes. The avirulence gene AvrPi12 was mapped in a population of 219 progeny derived from a cross between the two Mo isolates CHL42 and CHL357. A bulked segregant analysis indicated that the gene was located on chromosome 6, a conclusion borne out by an analysis of the pattern of segregation shown by individual isolates. Six additional PCR-based markers were developed to improve the map resolution in the key region. AvrPi12 was finally located within the sub-telomeric region of chromosome 6, distal to the SSR locus LSM6-5.

CONCLUSIONS: The improved SSR-based linkage map should be useful as a platform for gene mapping and isolation in Mo. It was used to establish the location of AvrPi12, thereby providing a starting point for its positional cloning.}, } @article {pmid29855267, year = {2018}, author = {Beauregard, F and Angers, B}, title = {Influence of genome and bio-ecology on the prevalence of genome exchange in unisexuals of the Ambystoma complex.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {82}, pmid = {29855267}, issn = {1471-2148}, support = {238600//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {Alleles ; Ambystoma/*genetics ; Amplified Fragment Length Polymorphism Analysis ; Animals ; *Ecological and Environmental Phenomena ; Genetic Loci ; Genetic Variation ; *Genome ; Genotype ; Geography ; Microsatellite Repeats/genetics ; Ploidies ; Reproduction/genetics ; }, abstract = {BACKGROUND: Unisexuals of the blue-spotted salamander complex are thought to reproduce by kleptogenesis. Genome exchanges associated with this sperm-dependent mode of reproduction are expected to result in a higher genetic variation and multiple ploidy levels compared to clonality. However, the existence of some populations exclusively formed of genetically identical individuals suggests that factors could prevent genome exchanges. This study aimed at assessing the prevalence of genome exchange among unisexuals of the Ambystoma laterale-jeffersonianum complex from 10 sites in the northern part of their distribution.

RESULTS: A total of 235 individuals, including 207 unisexuals, were genotyped using microsatellite loci and AFLP. Unisexual individuals could be sorted in five genetically distinct groups, likely derived from the same paternal A. jeffersonianum haplome. One of these groups exclusively reproduced clonally, even when found in sympatry with lineages presenting signature of genome exchange. Genome exchange was site-dependent for another group. Genome exchange was detected at all sites for the three remaining groups.

CONCLUSION: Prevalence of genome exchange appears to be associated with ecological conditions such as availability of effective sperm donors. Intrinsic genomic factors may also affect this process, since different lineages in sympatry present highly variable rate of genome exchange. The coexistence of clonal and genetically diversified lineages opens the door to further research on alternatives to genetic variation.}, } @article {pmid29855262, year = {2018}, author = {Song, GQ and Chen, Q}, title = {Comparative transcriptome analysis of nonchilled, chilled, and late-pink bud reveals flowering pathway genes involved in chilling-mediated flowering in blueberry.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {98}, pmid = {29855262}, issn = {1471-2229}, mesh = {Blueberry Plants/*genetics/physiology ; Cold Temperature ; Flowers/*genetics/physiology ; Freezing ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; Plant Growth Regulators/metabolism ; Plant Proteins/*genetics ; Sequence Analysis, RNA ; *Transcriptome ; Up-Regulation ; }, abstract = {BACKGROUND: Blueberry cultivars require a fixed quantity of chilling hours during winter endo-dormancy for vernalization. In this study, transcriptome analysis using RNA sequencing data from nonchilled, chilled, and late pink buds of southern highbush blueberry 'Legacy' was performed to reveal genes associated with chilling accumulation and bud break.

RESULTS: Fully chilled 'Legacy' plants flowered normally whereas nonchilled plants could not flower. Compared to nonchilled flower buds, chilled flower buds showed differential expression of 89% of flowering pathway genes, 86% of MADS-box genes, and 84% of cold-regulated genes. Blueberry orthologues of FLOWERING LOCUS T (FT) did not show a differential expression in chilled flower buds (compared to nonchilled flower bud) but were up-regulated in late-pink buds (compared to chilled flower bud). Orthologoues of major MADS-box genes were significantly up-regulated in chilled flower buds and down-regulated in late-pink buds. Functional orthologues of FLOWERING LOCUS C (FLC) were not found in blueberry. Orthologues of Protein FD (FD), TERMINAL FLOWER 1 (TFL1), and LEAFY (LFY) were down-regulated in chilled flower buds and in late-pink buds compared to nonchilled flower bud.

CONCLUSIONS: The changes from nonchilled to chilled and chilled to late-pink buds are associated with transcriptional changes in a large number of differentially expressed (DE) phytohormone-related genes and DE flowering pathway genes. The profile of DE genes suggests that orthologues of FT, FD, TFL1, LFY, and MADS-box genes are the major genes involved in chilling-mediated blueberry bud-break. The results contribute to the comprehensive investigation of the vernalization-mediated flowering mechanism in woody plants.}, } @article {pmid29855260, year = {2018}, author = {Thegerström, J and Matuschek, E and Su, YC and Riesbeck, K and Resman, F}, title = {A novel PBP3 substitution in Haemophilus influenzae confers reduced aminopenicillin susceptibility.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {48}, pmid = {29855260}, issn = {1471-2180}, abstract = {BACKGROUND: Identification and characterization of non-typeable Haemophilus influenzae (NTHi) with reduced susceptibility to β-lactam antibiotics due to mutations in penicillin binding protein 3 (PBP3) is a clinical challenge. We analyzed a blood isolate, NTHi93-57485, that was categorized as aminopenicillin resistant but lacked key amino acid substitutions in PBP3 that have previously been associated with reduced aminopenicillin susceptibility. The significance of an alternative amino acid substitution (Y528H) in this isolate was examined.

RESULTS: Site-directed mutagenesis of a β-lactam susceptible H. influenzae (NTHi3655) was performed to introduce the Y528H substitution into wild-type ftsI (encoding for PBP3). Disc diffusion screening and broth microdilution determination of MICs for β-lactam agents were done with the NTHi3655-PBP3Y528H mutant and were compared with the NTHi3655 wild-type as well as the original clinical isolate NTHi93-57485. Introduction of the Y528H substitution in NTHi3655 resulted in positive screening for β-lactam resistance. MICs for aminopenicillins were increased in the mutant compared to the wild-type. However, the mutant remained susceptible to aminopenicillins according to EUCAST clinical breakpoints (assuming intravenous treatment) and the introduction of Y528H alone did not increase the resistance to the same level as NTHi93-57485. None of the isolates had frame shift insertions in the acrR gene regulating the AcrAB efflux pump.

CONCLUSIONS: In parallel to the previously well-described PBP3-substitutions R517H and N526K, we demonstrate that Y528H confers reduced aminopenicillin susceptibility.}, } @article {pmid29855259, year = {2018}, author = {Willcocks, SJ and Stabler, RA and Atkins, HS and Oyston, PF and Wren, BW}, title = {High-throughput analysis of Yersinia pseudotuberculosis gene essentiality in optimised in vitro conditions, and implications for the speciation of Yersinia pestis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {46}, pmid = {29855259}, issn = {1471-2180}, abstract = {BACKGROUND: Yersinia pseudotuberculosis is a zoonotic pathogen, causing mild gastrointestinal infection in humans. From this comparatively benign pathogenic species emerged the highly virulent plague bacillus, Yersinia pestis, which has experienced significant genetic divergence in a relatively short time span. Much of our knowledge of Yersinia spp. evolution stems from genomic comparison and gene expression studies. Here we apply transposon-directed insertion site sequencing (TraDIS) to describe the essential gene set of Y. pseudotuberculosis IP32953 in optimised in vitro growth conditions, and contrast these with the published essential genes of Y. pestis.

RESULTS: The essential genes of an organism are the core genetic elements required for basic survival processes in a given growth condition, and are therefore attractive targets for antimicrobials. One such gene we identified is yptb3665, which encodes a peptide deformylase, and here we report for the first time, the sensitivity of Y. pseudotuberculosis to actinonin, a deformylase inhibitor. Comparison of the essential genes of Y. pseudotuberculosis with those of Y. pestis revealed the genes whose importance are shared by both species, as well as genes that were differentially required for growth. In particular, we find that the two species uniquely rely upon different iron acquisition and respiratory metabolic pathways under similar in vitro conditions.

CONCLUSIONS: The discovery of uniquely essential genes between the closely related Yersinia spp. represent some of the fundamental, species-defining points of divergence that arose during the evolution of Y. pestis from its ancestor. Furthermore, the shared essential genes represent ideal candidates for the development of novel antimicrobials against both species.}, } @article {pmid29855258, year = {2018}, author = {Wang, H and Tang, L and Wei, H and Lu, J and Mu, C and Wang, C}, title = {Transcriptomic analysis of adaptive mechanisms in response to sudden salinity drop in the mud crab, Scylla paramamosain.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {421}, pmid = {29855258}, issn = {1471-2164}, support = {2016C02055-8//Major Sci & Tech Special Project of Zhejiang Province/ ; CARS-48//Ministry of Agriculture of China & China Agriculture Research System/ ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; Brachyura/*genetics/*physiology ; *Gene Expression Profiling ; Gene Ontology ; Gills/metabolism ; Molecular Sequence Annotation ; Phenotype ; *Salinity ; }, abstract = {BACKGROUND: Scylla paramamosain (Crustacea: Decapoda: Portunidae: Syclla De Hann) is a commercially important mud crab distributed along the coast of southern China and other Indo-Pacific countries (Lin Z, Hao M, Zhu D, et al, Comp Biochem Physiol B Biochem Mol Biol 208-209:29-37, 2017; Walton ME, Vay LL, Lebata JH, et al, Estuar Coast Shelf Sci 66(3-4):493-500, 2006; Wang Z, Sun B, Zhu F, Fish Shellfish Immunol 67:612-9, 2017). While S. paramamosain is a euryhaline species, a sudden drop in salinity induces a negative impact on growth, molting, and reproduction, and may even cause death. The mechanism of osmotic regulation of marine crustaceans has been recently under investigation. However, the mechanism of adapting to a sudden drop in salinity has not been reported.

METHODS: In this study, transcriptomics analysis was conducted on the gills of S. paramamosain to test its adaptive capabilities over 120 h with a sudden drop in salinity from 23 ‰ to 3 ‰.

RESULTS: At the level of transcription, 135 DEGs (108 up-regulated and 27 down-regulated) annotated by NCBI non-redundant (nr) protein database were screened. GO analysis showed that the catalytic activity category showed the most participating genes in the 24 s-tier GO terms, indicating that intracellular metabolic activities in S. paramamosain were enhanced. Of the 164 mapped KEGG pathways, seven of the top 20 pathways were closely related to regulation of the Na+ / K+ -ATPase. Seven additional amino acid metabolism-related pathways were also found, along with other important signaling pathways.

CONCLUSION: Ion transport and amino acid metabolism were key factors in regulating the salinity adaptation of S. paramamosain in addition to several important signaling pathways.}, } @article {pmid29855256, year = {2018}, author = {Zhu, W and Liu, L and Wang, X and Gao, X and Jiang, J and Wang, B}, title = {Transcriptomics reveals the molecular processes of light-induced rapid darkening of the non-obligate cave dweller Oreolalax rhodostigmatus (Megophryidae, Anura) and their genetic basis of pigmentation strategy.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {422}, pmid = {29855256}, issn = {1471-2164}, support = {NSFC-31201702//National Natural Sciences Foundation of China/ ; NSFC-31471964//National Natural Sciences Foundation of China/ ; 2017YFC0505202//National Key Programme of Research and Development, Ministry of Science and Technology/ ; XDPB0202//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; XDA19050201//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; KJZG-EW-L13//Important Research Project of Chinese Academy of Sciences/ ; Y7C3041//2017 Western Light Talent Culture Project of the Chinese Academy of Sciences/ ; }, mesh = {Animals ; Anura/*genetics/*metabolism ; *Caves ; *Gene Expression Profiling ; Kinetics ; *Light ; Pigmentation/*genetics/*radiation effects ; RNA, Messenger/genetics ; }, abstract = {BACKGROUND: Vertebrates use different pigmentation strategies to adapt to various environments. A large amount of research has been done on disclosing the mechanisms of pigmentation strategies in vertebrates either under light, or, living in constant darkness. However, less attention has been paid to non-obligate, darkness dwellers. Red-spotted toothed toads Oreolalax rhodostigmatus (Megophryidae; Anura) from the karst mountainous region of southwestern China are non-obligate cave dwellers. Most tadpoles of the species possess transparent skin as they inhabit the dark karst caves. But remarkably, the transparent tadpoles can darken just within 15 h once exposed to light. Obviously, it is very significant to reveal molecular mechanisms of the unexpected rapid-darkening phenomenon.

RESULTS: We compared the transcriptomes of O. rhodostigmatus tadpoles with different durations of light exposure to investigate the cellular processes and potential regulation signals for their light-induced rapid darkening. Genes involved in melanogenesis (i.e. TYR, TYRP1 and DCT) and melanocyte proliferation, as well as their transcriptional factor (MITF), showed light-induced transcription, suggesting a dominating role of morphological color change (MCC) in this process. Transcription of genes related to growth factor, MAPK and PI3K-Akt pathways increased with time of light exposure, suggesting that light could induce significant growth signal, which might facilitate the rapid skin darkening. Most importantly, an in-frame deletion of four residues was identified in O. rhodostigmatus melanocortin-1 receptor (MC1R), a critical receptor in MCC. This deletion results in a more negatively charged ligand pocket with three stereo-tandem aspartate residues. Such structural changes likely decrease the constitutive activity of MC1R, but increase its ligands-dependent activity, thus coordinating pigment regression and rapid melanogenesis in the dark and light, respectively.

CONCLUSION: Our study suggested that rapid MCC was responsible for the light-induced rapid darkening of O. rhodostigmatus tadpoles. Genetic mutations of MC1R in them could explain how these non-obligate cave dwellers coordinate pigment regression and robust melanogenesis in darkness and light, respectively. To our knowledge, this is the first study that reports the association between pigmentation phenotype adaptation and MC1R mutations in amphibians and/or in non-obligate cave dwellers.}, } @article {pmid29854066, year = {2018}, author = {Fillmer, K and Adkins, S and Pongam, P and D'Elia, T}, title = {Using Tobamoviruses for Phylogenetic Instruction in Undergraduate Biology Courses.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29854066}, issn = {1935-7877}, } @article {pmid29854065, year = {2018}, author = {Ballen, CJ and Thompson, SK and Blum, JE and Newstrom, NP and Cotner, S}, title = {Discovery and Broad Relevance May Be Insignificant Components of Course-Based Undergraduate Research Experiences (CUREs) for Non-Biology Majors.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29854065}, issn = {1935-7877}, support = {R01 CE001210/CE/NCIPC CDC HHS/United States ; R49 CE000265/CE/NCIPC CDC HHS/United States ; }, abstract = {Course-based undergraduate research experiences (CUREs) are a type of laboratory learning environment associated with a science course, in which undergraduates participate in novel research. According to Auchincloss et al. (CBE Life Sci Educ 2104; 13:29-40), CUREs are distinct from other laboratory learning environments because they possess five core design components, and while national calls to improve STEM education have led to an increase in CURE programs nationally, less work has specifically focused on which core components are critical to achieving desired student outcomes. Here we use a backward elimination experimental design to test the importance of two CURE components for a population of non-biology majors: the experience of discovery and the production of data broadly relevant to the scientific or local community. We found nonsignificant impacts of either laboratory component on students' academic performance, science self-efficacy, sense of project ownership, and perceived value of the laboratory experience. Our results challenge the assumption that all core components of CUREs are essential to achieve positive student outcomes when applied at scale.}, } @article {pmid29854064, year = {2018}, author = {Vrentas, CE and Adler, JJ and Kleinschmit, AJ and Massimelli, J}, title = {Riboflavin Riboswitch Regulation: Hands-On Learning about the Role of RNA Structures in the Control of Gene Expression in Bacteria.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29854064}, issn = {1935-7877}, abstract = {American Society for Microbiology (ASM) Curriculum Guidelines highlight the importance of instruction about informational flow in organisms, including regulation of gene expression. However, foundational central dogma concepts and more advanced gene regulatory mechanisms are challenging for undergraduate biology students. To increase student comprehension of these principles, we designed an activity for upper-level biology students centered on construction and analysis of physical models of bacterial riboswitches. Students manipulate an inexpensive bag of supplies (beads, pipe cleaners) to model two conformations of a riboswitch in a bacterial transcript. After initial pilot testing, we implemented the activity in three upper-level classes at one research-intensive and two primarily undergraduate institutions. To assess student perceptions of learning gains, we utilized a pre/post-activity 5-point Likert-type survey instrument to characterize student perceptions of confidence in both their understanding of riboswitches and their ability to apply the central dogma to riboswitches. Median post-test ranks were significantly higher than median pre-test ranks (p < 0.0001) when compared by the Wilcoxon signed-rank test (n = 31). Next, we assessed post-activity knowledge via use of a rubric to score student responses on exam questions. More than 80% of students could correctly describe and diagram examples of riboswitches; data from initial iterations were used to enhance curriculum materials for subsequent implementations. We conclude that this riboswitch activity leads to both student-reported increases in confidence in the ASM curriculum dimension of gene regulation, including central dogma concepts, and demonstrated student ability to diagram riboswitches, predict outcomes of riboswitches, and connect riboswitches to evolutionary roles.}, } @article {pmid29854063, year = {2018}, author = {Hogan, DE and Harmon, MJ and Brown-Hogan, KA and Maier, RM}, title = {Using ESStudios Microbial Growth Modeling Program to Improve Student Comprehension of Microbial Growth and Its Underlying Mathematics.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, pmid = {29854063}, issn = {1935-7877}, support = {P30 ES006694/ES/NIEHS NIH HHS/United States ; }, } @article {pmid29854062, year = {2018}, author = {Zambito Ivey, JL and Myer, PR}, title = {Interactive Web-Based Tool for Nutritional Microbiology in Applied Agriculture Outreach.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {2}, pages = {}, doi = {10.1128/jmbe.v19i2.1557}, pmid = {29854062}, issn = {1935-7877}, } @article {pmid29853689, year = {2018}, author = {Bradshaw, N}, title = {Finding a community in the lab.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1038}, doi = {10.1126/science.360.6392.1038}, pmid = {29853689}, issn = {1095-9203}, } @article {pmid29853688, year = {2018}, author = {Ebenesersdóttir, SS and Sandoval-Velasco, M and Gunnarsdóttir, ED and Jagadeesan, A and Guðmundsdóttir, VB and Thordardóttir, EL and Einarsdóttir, MS and Moore, KHS and Sigurðsson, Á and Magnúsdóttir, DN and Jónsson, H and Snorradóttir, S and Hovig, E and Møller, P and Kockum, I and Olsson, T and Alfredsson, L and Hansen, TF and Werge, T and Cavalleri, GL and Gilbert, E and Lalueza-Fox, C and Walser, JW and Kristjánsdóttir, S and Gopalakrishnan, S and Árnadóttir, L and Magnússon, ÓÞ and Gilbert, MTP and Stefánsson, K and Helgason, A}, title = {Ancient genomes from Iceland reveal the making of a human population.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1028-1032}, doi = {10.1126/science.aar2625}, pmid = {29853688}, issn = {1095-9203}, mesh = {*Biological Evolution ; DNA, Ancient ; Female ; Founder Effect ; Gene Pool ; *Genetic Drift ; *Genome, Human ; Genotype ; Humans ; Iceland ; Male ; Phenotype ; Population/*genetics ; }, abstract = {Opportunities to directly study the founding of a human population and its subsequent evolutionary history are rare. Using genome sequence data from 27 ancient Icelanders, we demonstrate that they are a combination of Norse, Gaelic, and admixed individuals. We further show that these ancient Icelanders are markedly more similar to their source populations in Scandinavia and the British-Irish Isles than to contemporary Icelanders, who have been shaped by 1100 years of extensive genetic drift. Finally, we report evidence of unequal contributions from the ancient founders to the contemporary Icelandic gene pool. These results provide detailed insights into the making of a human population that has proven extraordinarily useful for the discovery of genotype-phenotype associations.}, } @article {pmid29853687, year = {2018}, author = {Scheib, CL and Li, H and Desai, T and Link, V and Kendall, C and Dewar, G and Griffith, PW and Mörseburg, A and Johnson, JR and Potter, A and Kerr, SL and Endicott, P and Lindo, J and Haber, M and Xue, Y and Tyler-Smith, C and Sandhu, MS and Lorenz, JG and Randall, TD and Faltyskova, Z and Pagani, L and Danecek, P and O'Connell, TC and Martz, P and Boraas, AS and Byrd, BF and Leventhal, A and Cambra, R and Williamson, R and Lesage, L and Holguin, B and Ygnacio-De Soto, E and Rosas, J and Metspalu, M and Stock, JT and Manica, A and Scally, A and Wegmann, D and Malhi, RS and Kivisild, T}, title = {Ancient human parallel lineages within North America contributed to a coastal expansion.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1024-1027}, doi = {10.1126/science.aar6851}, pmid = {29853687}, issn = {1095-9203}, support = {//European Research Council/International ; //Wellcome Trust/United Kingdom ; }, mesh = {*Biological Evolution ; California ; *Emigration and Immigration ; *Genome, Human ; Humans ; Ontario ; Population/*genetics ; }, abstract = {Little is known regarding the first people to enter the Americas and their genetic legacy. Genomic analysis of the oldest human remains from the Americas showed a direct relationship between a Clovis-related ancestral population and all modern Central and South Americans as well as a deep split separating them from North Americans in Canada. We present 91 ancient human genomes from California and Southwestern Ontario and demonstrate the existence of two distinct ancestries in North America, which possibly split south of the ice sheets. A contribution from both of these ancestral populations is found in all modern Central and South Americans. The proportions of these two ancestries in ancient and modern populations are consistent with a coastal dispersal and multiple admixture events.}, } @article {pmid29853686, year = {2018}, author = {Chen, MK and Rohla, R}, title = {The effect of partisanship and political advertising on close family ties.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1020-1024}, doi = {10.1126/science.aaq1433}, pmid = {29853686}, issn = {1095-9203}, mesh = {*Advertising as Topic ; Attitude ; *Family Characteristics ; Humans ; *Politics ; United States ; }, abstract = {Research on growing American political polarization and antipathy primarily studies public institutions and political processes, ignoring private effects, including strained family ties. Using anonymized smartphone-location data and precinct-level voting, we show that Thanksgiving dinners attended by residents from opposing-party precincts were 30 to 50 minutes shorter than same-party dinners. This decline from a mean of 257 minutes survives extensive spatial and demographic controls. Reductions in the duration of Thanksgiving dinner in 2016 tripled for travelers from media markets with heavy political advertising-an effect not observed in 2015-implying a relationship to election-related behavior. Effects appear asymmetric: Although fewer Democratic-precinct residents traveled in 2016 than in 2015, Republican-precinct residents shortened their Thanksgiving dinners by more minutes in response to political differences. Nationwide, 34 million hours of cross-partisan Thanksgiving dinner discourse were lost in 2016 owing to partisan effects.}, } @article {pmid29853685, year = {2018}, author = {Lapiedra, O and Schoener, TW and Leal, M and Losos, JB and Kolbe, JJ}, title = {Predator-driven natural selection on risk-taking behavior in anole lizards.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1017-1020}, doi = {10.1126/science.aap9289}, pmid = {29853685}, issn = {1095-9203}, mesh = {Animals ; Lizards/*genetics/*physiology ; *Predatory Behavior ; *Risk-Taking ; *Selection, Genetic ; }, abstract = {Biologists have long debated the role of behavior in evolution, yet understanding of its role as a driver of adaptation is hampered by the scarcity of experimental studies of natural selection on behavior in nature. After showing that individual Anolis sagrei lizards vary consistently in risk-taking behaviors, we experimentally established populations on eight small islands either with or without Leiocephalus carinatus, a major ground predator. We found that selection predictably favors different risk-taking behaviors under different treatments: Exploratory behavior is favored in the absence of predators, whereas avoidance of the ground is favored in their presence. On predator islands, selection on behavior is stronger than selection on morphology, whereas the opposite holds on islands without predators. Our field experiment demonstrates that selection can shape behavioral traits, paving the way toward adaptation to varying environmental contexts.}, } @article {pmid29853684, year = {2018}, author = {Chen, M and Penfield, S}, title = {Feedback regulation of COOLAIR expression controls seed dormancy and flowering time.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1014-1017}, doi = {10.1126/science.aar7361}, pmid = {29853684}, issn = {1095-9203}, mesh = {Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins/*genetics/physiology ; Chromatin/metabolism ; Flowers/genetics/*growth & development ; *Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; Germination/genetics/physiology ; MADS Domain Proteins/*genetics/physiology ; Plant Dormancy/*genetics/physiology ; RNA, Antisense/metabolism ; Seasons ; Seeds/*genetics/growth & development ; Temperature ; Transcription, Genetic ; }, abstract = {Plants integrate seasonal signals, including temperature and day length, to optimize the timing of developmental transitions. Seasonal sensing requires the activity of two proteins, FLOWERING LOCUS C (FLC) and FLOWERING LOCUS T (FT), that control certain developmental transitions in plants. During reproductive development, the mother plant uses FLC and FT to modulate progeny seed dormancy in response to temperature. We found that for regulation of seed dormancy, FLC and FT function in opposite configuration to how those same genes control time to flowering. For seed dormancy, FT regulates seed dormancy through FLC gene expression and regulates chromatin state by activating antisense FLC transcription. Thus, in Arabidopsis the same genes controlled in opposite format regulate flowering time and seed dormancy in response to the temperature changes that characterize seasons.}, } @article {pmid29853683, year = {2018}, author = {Le, C and Chen, TQ and Liang, T and Zhang, P and MacMillan, DWC}, title = {A radical approach to the copper oxidative addition problem: Trifluoromethylation of bromoarenes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1010-1014}, doi = {10.1126/science.aat4133}, pmid = {29853683}, issn = {1095-9203}, support = {R01 GM103558/GM/NIGMS NIH HHS/United States ; }, abstract = {Transition metal-catalyzed arene functionalization has been widely used for molecular synthesis over the past century. In this arena, copper catalysis has long been considered a privileged platform due to the propensity of high-valent copper to undergo reductive elimination with a wide variety of coupling fragments. However, the sluggish nature of oxidative addition has limited copper's capacity to broadly facilitate haloarene coupling protocols. Here, we demonstrate that this copper oxidative addition problem can be overcome with an aryl radical-capture mechanism, wherein the aryl radical is generated through a silyl radical halogen abstraction. This strategy was applied to a general trifluoromethylation of aryl bromides through dual copper-photoredox catalysis. Mechanistic studies support the formation of an open-shell aryl species.}, } @article {pmid29853682, year = {2018}, author = {Kim, Y and Chortos, A and Xu, W and Liu, Y and Oh, JY and Son, D and Kang, J and Foudeh, AM and Zhu, C and Lee, Y and Niu, S and Liu, J and Pfattner, R and Bao, Z and Lee, TW}, title = {A bioinspired flexible organic artificial afferent nerve.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {998-1003}, doi = {10.1126/science.aao0098}, pmid = {29853682}, issn = {1095-9203}, mesh = {*Afferent Pathways ; *Biomimetic Materials ; Mechanoreceptors ; Motor Neurons ; Muscle Contraction ; Muscles/innervation/physiology ; *Neural Prostheses ; Pressure ; Robotics ; }, abstract = {The distributed network of receptors, neurons, and synapses in the somatosensory system efficiently processes complex tactile information. We used flexible organic electronics to mimic the functions of a sensory nerve. Our artificial afferent nerve collects pressure information (1 to 80 kilopascals) from clusters of pressure sensors, converts the pressure information into action potentials (0 to 100 hertz) by using ring oscillators, and integrates the action potentials from multiple ring oscillators with a synaptic transistor. Biomimetic hierarchical structures can detect movement of an object, combine simultaneous pressure inputs, and distinguish braille characters. Furthermore, we connected our artificial afferent nerve to motor nerves to construct a hybrid bioelectronic reflex arc to actuate muscles. Our system has potential applications in neurorobotics and neuroprosthetics.}, } @article {pmid29853681, year = {2018}, author = {Telfer, MW and Parteli, EJR and Radebaugh, J and Beyer, RA and Bertrand, T and Forget, F and Nimmo, F and Grundy, WM and Moore, JM and Stern, SA and Spencer, J and Lauer, TR and Earle, AM and Binzel, RP and Weaver, HA and Olkin, CB and Young, LA and Ennico, K and Runyon, K and , and Buie, M and Buratti, B and Cheng, A and Kavelaars, JJ and Linscott, I and McKinnon, WB and Reitsema, H and Reuter, D and Schenk, P and Showalter, M and Tyler, L}, title = {Dunes on Pluto.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {992-997}, doi = {10.1126/science.aao2975}, pmid = {29853681}, issn = {1095-9203}, abstract = {The surface of Pluto is more geologically diverse and dynamic than had been expected, but the role of its tenuous atmosphere in shaping the landscape remains unclear. We describe observations from the New Horizons spacecraft of regularly spaced, linear ridges whose morphology, distribution, and orientation are consistent with being transverse dunes. These are located close to mountainous regions and are orthogonal to nearby wind streaks. We demonstrate that the wavelength of the dunes (~0.4 to 1 kilometer) is best explained by the deposition of sand-sized (~200 to ~300 micrometer) particles of methane ice in moderate winds (<10 meters per second). The undisturbed morphology of the dunes, and relationships with the underlying convective glacial ice, imply that the dunes have formed in the very recent geological past.}, } @article {pmid29853680, year = {2018}, author = {Poore, J and Nemecek, T}, title = {Reducing food's environmental impacts through producers and consumers.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {987-992}, doi = {10.1126/science.aaq0216}, pmid = {29853680}, issn = {1095-9203}, mesh = {Animal Feed ; Animals ; Aquaculture ; Crop Production ; *Environment ; Feeding Behavior ; *Food ; Food Packaging ; *Food Supply ; Humans ; Livestock ; }, abstract = {Food's environmental impacts are created by millions of diverse producers. To identify solutions that are effective under this heterogeneity, we consolidated data covering five environmental indicators; 38,700 farms; and 1600 processors, packaging types, and retailers. Impact can vary 50-fold among producers of the same product, creating substantial mitigation opportunities. However, mitigation is complicated by trade-offs, multiple ways for producers to achieve low impacts, and interactions throughout the supply chain. Producers have limits on how far they can reduce impacts. Most strikingly, impacts of the lowest-impact animal products typically exceed those of vegetable substitutes, providing new evidence for the importance of dietary change. Cumulatively, our findings support an approach where producers monitor their own impacts, flexibly meet environmental targets by choosing from multiple practices, and communicate their impacts to consumers.}, } @article {pmid29853679, year = {2018}, author = {Kao, J and Sutherland, SPH}, title = {Science transcends cultures in Taiwan.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {974}, doi = {10.1126/science.aat6407}, pmid = {29853679}, issn = {1095-9203}, } @article {pmid29853678, year = {2018}, author = {Payne, JM}, title = {U.S. budget targets fish and wildlife work.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {973-974}, doi = {10.1126/science.aat9562}, pmid = {29853678}, issn = {1095-9203}, mesh = {Animals ; Budgets ; Conservation of Natural Resources/*economics ; Ecosystem ; *Fishes ; }, } @article {pmid29853677, year = {2018}, author = {Goulson, D and , }, title = {Call to restrict neonicotinoids.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {973}, doi = {10.1126/science.aau0432}, pmid = {29853677}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; *Insect Control ; Insecta/*drug effects ; Insecticides/*adverse effects ; Neonicotinoids/*adverse effects ; Neurotoxins/*adverse effects ; }, } @article {pmid29853676, year = {2018}, author = {Leshner, AI}, title = {Student-centered, modernized graduate STEM education.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {969-970}, doi = {10.1126/science.aau0590}, pmid = {29853676}, issn = {1095-9203}, } @article {pmid29853675, year = {2018}, author = {Harland, RM}, title = {A new view of embryo development and regeneration.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {967-968}, doi = {10.1126/science.aat8413}, pmid = {29853675}, issn = {1095-9203}, mesh = {Embryo, Nonmammalian ; *Embryonic Development ; *Regeneration ; }, } @article {pmid29853674, year = {2018}, author = {Bartolozzi, C}, title = {Neuromorphic circuits impart a sense of touch.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {966-967}, doi = {10.1126/science.aat3125}, pmid = {29853674}, issn = {1095-9203}, mesh = {*Models, Neurological ; Synapses ; *Touch ; }, } @article {pmid29853673, year = {2018}, author = {Achilli, A and Olivieri, A and Semino, O and Torroni, A}, title = {Ancient human genomes-keys to understanding our past.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {964-965}, doi = {10.1126/science.aat7257}, pmid = {29853673}, issn = {1095-9203}, mesh = {*Evolution, Molecular ; *Genome, Human ; Humans ; }, } @article {pmid29853672, year = {2018}, author = {Muir, A and Vander Heiden, MG}, title = {The nutrient environment affects therapy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {962-963}, doi = {10.1126/science.aar5986}, pmid = {29853672}, issn = {1095-9203}, support = {F32 CA213810/CA/NCI NIH HHS/United States ; R01 CA168653/CA/NCI NIH HHS/United States ; R01 CA201276/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Drug Resistance, Neoplasm ; Humans ; Metabolic Networks and Pathways ; Neoplasms/*drug therapy/genetics/*metabolism ; Precision Medicine ; *Tumor Microenvironment ; }, } @article {pmid29853671, year = {2018}, author = {Hayes, AG}, title = {Dunes across the Solar System.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {960-961}, doi = {10.1126/science.aat7488}, pmid = {29853671}, issn = {1095-9203}, } @article {pmid29853670, year = {2018}, author = {van Straalen, NM and Legler, J}, title = {Decision-making in a storm of discontent.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {958-960}, doi = {10.1126/science.aat0567}, pmid = {29853670}, issn = {1095-9203}, mesh = {Animal Husbandry ; Animals ; *Decision Making ; *Drug Approval ; Europe ; European Union ; Glycine/adverse effects/*analogs & derivatives ; Herbicides/*adverse effects ; Humans ; Plant Weeds ; Risk Assessment ; Weed Control/*methods ; }, } @article {pmid29853669, year = {2018}, author = {Cho, A}, title = {The galaxy builders.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {954-957}, doi = {10.1126/science.360.6392.954}, pmid = {29853669}, issn = {1095-9203}, } @article {pmid29853668, year = {2018}, author = {Warren, M}, title = {United Kingdom unveils ambitious air pollution plan.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {953}, doi = {10.1126/science.360.6392.953}, pmid = {29853668}, issn = {1095-9203}, mesh = {Air Pollution/*prevention & control ; United States ; }, } @article {pmid29853667, year = {2018}, author = {Rabesandratana, T}, title = {Europe's science spending set for another big boost.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {952-953}, doi = {10.1126/science.360.6392.952}, pmid = {29853667}, issn = {1095-9203}, } @article {pmid29853666, year = {2018}, author = {Pennisi, E}, title = {New copies of old gene drove brain expansion.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {951}, doi = {10.1126/science.360.6392.951}, pmid = {29853666}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Brain/*growth & development ; DNA Replication ; *Gene Dosage ; *Gene Duplication ; *Gene Expression Regulation, Developmental ; Hominidae ; Humans ; Receptor, Notch2/*genetics ; }, } @article {pmid29853665, year = {2018}, author = {Wadman, M}, title = {Will U.S. academies expel sexual harassers?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {949-950}, doi = {10.1126/science.360.6392.949}, pmid = {29853665}, issn = {1095-9203}, mesh = {*National Academy of Sciences (U.S.) ; *Scientific Misconduct ; Sexual Harassment/*ethics ; United States ; }, } @article {pmid29853664, year = {2018}, author = {Cornwall, W}, title = {Scientists aim to smoke out wildfire impacts.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {948-949}, doi = {10.1126/science.360.6392.948}, pmid = {29853664}, issn = {1095-9203}, mesh = {*Environment ; *Health ; Humans ; Smoke/*adverse effects ; United States ; *Wildfires ; }, } @article {pmid29853663, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {944-946}, doi = {10.1126/science.360.6392.944}, pmid = {29853663}, issn = {1095-9203}, } @article {pmid29853662, year = {2018}, author = {Hayhoe, K}, title = {When facts are not enough.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {943}, doi = {10.1126/science.aau2565}, pmid = {29853662}, issn = {1095-9203}, } @article {pmid29853555, year = {2018}, author = {Patriarchi, T and Cho, JR and Merten, K and Howe, MW and Marley, A and Xiong, WH and Folk, RW and Broussard, GJ and Liang, R and Jang, MJ and Zhong, H and Dombeck, D and von Zastrow, M and Nimmerjahn, A and Gradinaru, V and Williams, JT and Tian, L}, title = {Ultrafast neuronal imaging of dopamine dynamics with designed genetically encoded sensors.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {}, pmid = {29853555}, issn = {1095-9203}, support = {DP2 NS087949/NS/NINDS NIH HHS/United States ; R01 NS085938/NS/NINDS NIH HHS/United States ; R01 DA004523/DA/NIDA NIH HHS/United States ; R01 MH110556/MH/NIMH NIH HHS/United States ; R01 NS104944/NS/NINDS NIH HHS/United States ; U01 NS094247/NS/NINDS NIH HHS/United States ; DP2 NS083038/NS/NINDS NIH HHS/United States ; R01 AG047664/AG/NIA NIH HHS/United States ; U01 NS090604/NS/NINDS NIH HHS/United States ; U01 NS103522/NS/NINDS NIH HHS/United States ; DP2 MH107056/MH/NIMH NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Biosensing Techniques ; Calcium/analysis/metabolism ; Cerebral Cortex/chemistry/*metabolism ; Corpus Striatum ; Dopamine/analysis/*metabolism ; Genetic Engineering ; Green Fluorescent Proteins/chemistry/genetics ; Humans ; Learning ; Mice ; Neuroimaging/*methods ; Neurons/physiology ; Neurotransmitter Agents/analysis/*metabolism ; *Optogenetics ; Receptors, Dopamine D1/chemistry/genetics ; Serotonin/analysis/metabolism ; }, abstract = {Neuromodulatory systems exert profound influences on brain function. Understanding how these systems modify the operating mode of target circuits requires spatiotemporally precise measurement of neuromodulator release. We developed dLight1, an intensity-based genetically encoded dopamine indicator, to enable optical recording of dopamine dynamics with high spatiotemporal resolution in behaving mice. We demonstrated the utility of dLight1 by imaging dopamine dynamics simultaneously with pharmacological manipulation, electrophysiological or optogenetic stimulation, and calcium imaging of local neuronal activity. dLight1 enabled chronic tracking of learning-induced changes in millisecond dopamine transients in mouse striatum. Further, we used dLight1 to image spatially distinct, functionally heterogeneous dopamine transients relevant to learning and motor control in mouse cortex. We also validated our sensor design platform for developing norepinephrine, serotonin, melatonin, and opioid neuropeptide indicators.}, } @article {pmid29853554, year = {2018}, author = {Toda, S and Blauch, LR and Tang, SKY and Morsut, L and Lim, WA}, title = {Programming self-organizing multicellular structures with synthetic cell-cell signaling.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {156-162}, doi = {10.1126/science.aat0271}, pmid = {29853554}, issn = {1095-9203}, support = {K99 EB021030/EB/NIBIB NIH HHS/United States ; P50 GM081879/GM/NIGMS NIH HHS/United States ; T32 GM008412/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Artificial Cells ; Cell Adhesion ; *Cell Communication ; Cell Engineering/*methods ; *Cells ; *Morphogenesis ; Signal Transduction ; Spheroids, Cellular/cytology/physiology ; }, abstract = {A common theme in the self-organization of multicellular tissues is the use of cell-cell signaling networks to induce morphological changes. We used the modular synNotch juxtacrine signaling platform to engineer artificial genetic programs in which specific cell-cell contacts induced changes in cadherin cell adhesion. Despite their simplicity, these minimal intercellular programs were sufficient to yield assemblies with hallmarks of natural developmental systems: robust self-organization into multidomain structures, well-choreographed sequential assembly, cell type divergence, symmetry breaking, and the capacity for regeneration upon injury. The ability of these networks to drive complex structure formation illustrates the power of interlinking cell signaling with cell sorting: Signal-induced spatial reorganization alters the local signals received by each cell, resulting in iterative cycles of cell fate branching. These results provide insights into the evolution of multicellularity and demonstrate the potential to engineer customized self-organizing tissues or materials.}, } @article {pmid29853553, year = {2018}, author = {Reardon, PK and Seidlitz, J and Vandekar, S and Liu, S and Patel, R and Park, MTM and Alexander-Bloch, A and Clasen, LS and Blumenthal, JD and Lalonde, FM and Giedd, JN and Gur, RC and Gur, RE and Lerch, JP and Chakravarty, MM and Satterthwaite, TD and Shinohara, RT and Raznahan, A}, title = {Normative brain size variation and brain shape diversity in humans.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1222-1227}, doi = {10.1126/science.aar2578}, pmid = {29853553}, issn = {1095-9203}, support = {ZIA MH002794/MH/NIMH NIH HHS/United States ; R01 MH107235/MH/NIMH NIH HHS/United States ; R01 NS085211/NS/NINDS NIH HHS/United States ; R01 NS060910/NS/NINDS NIH HHS/United States ; R01 MH112847/MH/NIMH NIH HHS/United States ; R01 MH107703/MH/NIMH NIH HHS/United States ; U54 MH091657/MH/NIMH NIH HHS/United States ; }, mesh = {*Biological Evolution ; Brain/*anatomy & histology ; Humans ; Neuroimaging ; Organ Size ; }, abstract = {Brain size variation over primate evolution and human development is associated with shifts in the proportions of different brain regions. Individual brain size can vary almost twofold among typically developing humans, but the consequences of this for brain organization remain poorly understood. Using in vivo neuroimaging data from more than 3000 individuals, we find that larger human brains show greater areal expansion in distributed frontoparietal cortical networks and related subcortical regions than in limbic, sensory, and motor systems. This areal redistribution recapitulates cortical remodeling across evolution, manifests by early childhood in humans, and is linked to multiple markers of heightened metabolic cost and neuronal connectivity. Thus, human brain shape is systematically coupled to naturally occurring variations in brain size through a scaling map that integrates spatiotemporally diverse aspects of neurobiology.}, } @article {pmid29853552, year = {2018}, author = {Lu, W and Ridgwell, A and Thomas, E and Hardisty, DS and Luo, G and Algeo, TJ and Saltzman, MR and Gill, BC and Shen, Y and Ling, HF and Edwards, CT and Whalen, MT and Zhou, X and Gutchess, KM and Jin, L and Rickaby, REM and Jenkyns, HC and Lyons, TW and Lenton, TM and Kump, LR and Lu, Z}, title = {Late inception of a resiliently oxygenated upper ocean.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {174-177}, doi = {10.1126/science.aar5372}, pmid = {29853552}, issn = {1095-9203}, mesh = {Atmosphere/*chemistry ; *Biological Evolution ; Calcium/analysis ; Carbonates/analysis ; Iodine/analysis ; Oceans and Seas ; Oxygen/*analysis ; *Plankton ; }, abstract = {Rising oceanic and atmospheric oxygen levels through time have been crucial to enhanced habitability of surface Earth environments. Few redox proxies can track secular variations in dissolved oxygen concentrations around threshold levels for metazoan survival in the upper ocean. We present an extensive compilation of iodine-to-calcium ratios (I/Ca) in marine carbonates. Our record supports a major rise in the partial pressure of oxygen in the atmosphere at ~400 million years (Ma) ago and reveals a step change in the oxygenation of the upper ocean to relatively sustainable near-modern conditions at ~200 Ma ago. An Earth system model demonstrates that a shift in organic matter remineralization to greater depths, which may have been due to increasing size and biomineralization of eukaryotic plankton, likely drove the I/Ca signals at ~200 Ma ago.}, } @article {pmid29853273, year = {2018}, author = {Douze, K and Delagnes, A and Rots, V and Gravina, B}, title = {A reply to Sahle and Braun's reply to 'The pattern of emergence of a Middle Stone Age tradition at Gademotta and Kulkuletti (Ethiopia) through convergent tool and point technologies' [J. Hum. Evol. 91 (2016) 93-121].}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {207-214}, doi = {10.1016/j.jhevol.2018.04.015}, pmid = {29853273}, issn = {1095-8606}, abstract = {Sahle and Braun's (in press) recent comments on our identification (Douze and Delagnes, 2016) of diachronic trends in Middle Stone Age point traditions in several lithic assemblages from the sites of Gademotta and Kulkuletti (Ethiopia) focuses on pointed tool function rather than the gradual technological shifts we observed between sites. Here we address several of what we consider to be inaccuracies and misinterpretations concerning our work with the Gademotta and Kulkuletti lithic assemblages (Douze, 2012, 2014), more specifically, Sahle and Braun's (in press) interpretation of the tranchet blow technique. This discussion is inseparable from a critical review of the evidence advanced by Sahle and Braun to support projectile technology being present in the Gademotta Formation as early as >279 ka.}, } @article {pmid29853204, year = {2018}, author = {Tomkova, M and Schuster-Böckler, B}, title = {DNA Modifications: Naturally More Error Prone?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {627-638}, doi = {10.1016/j.tig.2018.04.005}, pmid = {29853204}, issn = {0168-9525}, abstract = {Epigenetic DNA modifications are essential for normal cell function in vertebrates, but they can also be hotspots of mutagenesis. Methylcytosine in particular has long been known to be less stable than other nucleotides and spontaneously deaminates to thymine. Beyond this well-established phenomenon, however, the influence of epigenetic marks on mutagenesis has recently become an active field of investigation. In this review, we summarize current knowledge of the interactions between different DNA modifications and other mutagenic processes. External mutagens, such as UV light or smoking carcinogens, affect modified cytosines differently from unmodified ones, and modified cytosine can in some cases be protective rather than mutagenic. Notably, cell-intrinsic processes, such as DNA replication, also appear to influence the mutagenesis of modified cytosines. Altogether, evidence is accumulating to show that epigenetic changes have a profound influence on tissue-specific mutation accumulation.}, } @article {pmid29853203, year = {2018}, author = {Bourque, G}, title = {Comparing Apples to Apples and Oranges to Oranges.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {571-572}, doi = {10.1016/j.tig.2018.05.002}, pmid = {29853203}, issn = {0168-9525}, abstract = {A new study sequenced and assembled two rodent genomes to better understand the evolutionary forces shaping mammalian genomes. Their results suggest multiple roles for genomic repeats.}, } @article {pmid29852218, year = {2018}, author = {Corbett, MK and Eksteen, JJ and Niu, XZ and Watkin, ELJ}, title = {Syntrophic effect of indigenous and inoculated microorganisms in the leaching of rare earth elements from Western Australian monazite.}, journal = {Research in microbiology}, volume = {169}, number = {10}, pages = {558-568}, doi = {10.1016/j.resmic.2018.05.007}, pmid = {29852218}, issn = {1769-7123}, mesh = {Australia ; Bacteria/classification/genetics/isolation & purification/*metabolism ; Biodiversity ; Fungi/classification/isolation & purification/metabolism ; Geologic Sediments/chemistry/microbiology ; Metals, Rare Earth/*metabolism ; Microbial Consortia ; Penicillium/metabolism ; }, abstract = {The unique physiochemical properties exhibited by rare earth elements (REEs) and their increasing application in high-tech industries has created a demand for secure supply lines with established recovery procedures that create minimal environmental damage. Bioleaching experiments conducted on a non-sterile monazite concentrate with a known phosphate solubilising microorganism (PSM) resulted in greater mobilisation of REEs into solution in comparison to experiments conducted on sterile monazite. By combining the native consortia with an introduced PSM, a syntrophic effect between the populations effectively leached a greater amount of REEs than either a single PSM or the indigenous population alone. With sterile monazite, Penicillium sp.CF1 inoculated experiments released a total REE concentration of 12.32 mg L-1 after incubation for 8 days, whereas on non-sterile ore, double the soluble REE concentration was recorded (23.7 mg L-1). Comparable effects were recorded with Enterobacter aerogenes, Pantoea agglomerans and Pseudomonas putida. Alterations in the microbial populations during bioleaching of the monazite ore were determined by diversity profiling and demonstrated noticeable changes in community inhabitants over 14 days. The presence of native Firmicutes on the monazite appears to greatly contribute to the increased leaching recorded when using non-sterile monazite for REE recovery.}, } @article {pmid29852217, year = {2018}, author = {Almeida, GM and Leppänen, M and Maasilta, IJ and Sundberg, LR}, title = {Bacteriophage imaging: past, present and future.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {488-494}, doi = {10.1016/j.resmic.2018.05.006}, pmid = {29852217}, issn = {1769-7123}, mesh = {Animals ; Bacteria/ultrastructure/virology ; Bacteriophages/chemistry/*ultrastructure ; History, 20th Century ; History, 21st Century ; Humans ; Microscopy/history/instrumentation/methods/trends ; Molecular Imaging/*history/methods/*trends ; Virion/*ultrastructure ; }, abstract = {The visualization of viral particles only became possible after the advent of the electron microscope. The first bacteriophage images were published in 1940 and were soon followed by many other publications that helped to elucidate the structure of the particles and their interaction with the bacterial hosts. As sample preparation improved and new technologies were developed, phage imaging became important approach to morphologically classify these viruses and helped to understand its importance in the biosphere. In this review we discuss the main milestones in phage imaging, how it affected our knowledge on these viruses and recent developments in the field.}, } @article {pmid29852132, year = {2018}, author = {Cesario, JM and Landin Malt, A and Chung, JU and Khairallah, MP and Dasgupta, K and Asam, K and Deacon, LJ and Choi, V and Almaidhan, AA and Darwiche, NA and Kim, J and Johnson, RL and Jeong, J}, title = {Anti-osteogenic function of a LIM-homeodomain transcription factor LMX1B is essential to early patterning of the calvaria.}, journal = {Developmental biology}, volume = {443}, number = {2}, pages = {103-116}, pmid = {29852132}, issn = {1095-564X}, support = {R01 DE026798/DE/NIDCR NIH HHS/United States ; R03 DE023617/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Body Patterning/physiology ; Bone Development/physiology ; Female ; Gene Expression Regulation, Developmental ; LIM-Homeodomain Proteins/genetics/*metabolism ; Male ; Mesoderm/physiology ; Mice ; Mice, Inbred C57BL ; Osteogenesis/physiology ; Skull/*embryology/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {The calvaria (upper part of the skull) is made of plates of bone and fibrous joints (sutures and fontanelles), and the proper balance and organization of these components are crucial to normal development of the calvaria. In a mouse embryo, the calvaria develops from a layer of head mesenchyme that surrounds the brain from shortly after mid-gestation. The mesenchyme just above the eye (supra-orbital mesenchyme, SOM) generates ossification centers for the bones, which then grow toward the apex gradually. In contrast, the mesenchyme apical to SOM (early migrating mesenchyme, EMM), including the area at the vertex, does not generate an ossification center. As a result, the dorsal midline of the head is occupied by sutures and fontanelles at birth. To date, the molecular basis for this regional difference in developmental programs is unknown. The current study provides vital insights into the genetic regulation of calvarial patterning. First, we showed that osteogenic signals were active in both EMM and SOM during normal development, which suggested the presence of an anti-osteogenic factor in EMM to counter the effect of these signals. Subsequently, we identified Lmx1b as an anti-osteogenic gene that was expressed in EMM but not in SOM. Furthermore, head mesenchyme-specific deletion of Lmx1b resulted in heterotopic ossification from EMM at the vertex, and craniosynostosis affecting multiple sutures. Conversely, forced expression of Lmx1b in SOM was sufficient to inhibit osteogenic specification. Therefore, we conclude that Lmx1b plays a key role as an anti-osteogenic factor in patterning the head mesenchyme into areas with different osteogenic competence. In turn, this patterning event is crucial to generating the proper organization of the bones and soft tissue joints of the calvaria.}, } @article {pmid29852131, year = {2018}, author = {Pla, P and Monsoro-Burq, AH}, title = {The neural border: Induction, specification and maturation of the territory that generates neural crest cells.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.05.018}, pmid = {29852131}, issn = {1095-564X}, abstract = {The neural crest is induced at the edge between the neural plate and the nonneural ectoderm, in an area called the neural (plate) border, during gastrulation and neurulation. In recent years, many studies have explored how this domain is patterned, and how the neural crest is induced within this territory, that also participates to the prospective dorsal neural tube, the dorsalmost nonneural ectoderm, as well as placode derivatives in the anterior area. This review highlights the tissue interactions, the cell-cell signaling and the molecular mechanisms involved in this dynamic spatiotemporal patterning, resulting in the induction of the premigratory neural crest. Collectively, these studies allow building a complex neural border and early neural crest gene regulatory network, mostly composed by transcriptional regulations but also, more recently, including novel signaling interactions.}, } @article {pmid29852088, year = {2019}, author = {Lee, C}, title = {Passing the Baton to the Next Generation: A Few Problems That Need Solving.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {1-13}, doi = {10.1146/annurev-marine-010318-095342}, pmid = {29852088}, issn = {1941-0611}, abstract = {This is a personal account of some of the people and factors that were important in my career in chemical oceanography. I also discuss two areas of oceanographic research and training that I think need more attention. The first is how the difficulty in getting appropriate samples hampers our ability to fully understand biogeochemical processes in the sea. I have worked on dissolved materials, suspended and sinking particles, and sediments in lakes, oceans, rivers, and aerosols. Sample collection problems affect all those areas, although to different degrees. Second, I discuss a few of the issues that I most worry about with regard to graduate education in oceanography, among them an apparent decrease over the past several decades in the ability of many beginning students to write clearly and think logically.}, } @article {pmid29852085, year = {2018}, author = {Seifert, HS}, title = {Above and Beyond Watson and Crick: Guanine Quadruplex Structures and Microbes.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {49-69}, doi = {10.1146/annurev-micro-090817-062629}, pmid = {29852085}, issn = {1545-3251}, abstract = {Advances in understanding mechanisms of nucleic acids have revolutionized molecular biology and medicine, but understanding of nontraditional nucleic acid conformations is less developed. The guanine quadruplex (G4) alternative DNA structure was first described in the 1960s, but the existence of G4 structures (G4-S) and their participation in myriads of biological functions are still underappreciated. Despite many tools to study G4s and many examples of roles for G4s in eukaryotic molecular processes and issues with uncontrolled G4-S formation, there is relatively little knowledge about the roles of G4-S in viral or prokaryotic systems. This review summarizes the state of the art with regard to G4-S in eukaryotes and their potential roles in human disease before discussing the evidence that G4-S have equivalent importance in affecting viral and bacterial life.}, } @article {pmid29852072, year = {2018}, author = {Holtzman, L and Gersbach, CA}, title = {Editing the Epigenome: Reshaping the Genomic Landscape.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {43-71}, doi = {10.1146/annurev-genom-083117-021632}, pmid = {29852072}, issn = {1545-293X}, support = {R01 DA036865/DA/NIDA NIH HHS/United States ; R21 NS103007/NS/NINDS NIH HHS/United States ; }, abstract = {The eukaryotic epigenome has an instrumental role in determining and maintaining cell identity and function. Epigenetic components such as DNA methylation, histone tail modifications, chromatin accessibility, and DNA architecture are tightly correlated with central cellular processes, while their dysregulation manifests in aberrant gene expression and disease. The ability to specifically edit the epigenome holds the promise of enhancing understanding of how epigenetic modifications function and enabling manipulation of cell phenotype for research or therapeutic purposes. Genome engineering technologies use highly specific DNA-targeting tools to precisely deposit epigenetic changes in a locus-specific manner, creating diverse epigenome editing platforms. This review summarizes these technologies and insights from recent studies, describes the complex relationship between epigenetic components and gene regulation, and highlights caveats and promises of the emerging field of epigenome editing, including applications for translational purposes, such as epigenetic therapy and regenerative medicine.}, } @article {pmid29851378, year = {2018}, author = {Li, X and Wang, Z and Lu, F and Zhang, H and Tian, J and He, L and Chu, Y and Tian, Y}, title = {Actinocorallia populi sp. nov., an endophytic actinomycete isolated from a root of Populus adenopoda (Maxim.).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2325-2330}, doi = {10.1099/ijsem.0.002840}, pmid = {29851378}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Endophytes ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Populus/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An endophytic actinobacterium, strain A251T, was isolated from the root of Populus adenopoda Maxim and subjected to characterization using polyphasic taxonomy. Analysis of the 16S rRNA gene sequence revealed that the isolate represented a member of the phylogenetic cluster of the genus Actinocorallia and was most closely related to Actinocorallia aurantiaca JCM 8201T (98.0 %) and Actinocorallia libanotica IFO 10495T (98.0 %). DNA-DNA hybridization values between A251T and these strains were 41.2 % and 45.0 %, respectively. The G+C content of the DNA was 71.5 mol%. Major fatty acids were C16 : 0, C16 : 1ω7c and C18 : 1ω9c. The peptidoglycan diamino acid of A251T was meso-diaminopimelic acid and the whole-cell hydrolysates contained glucose and ribose. The major menaquinones were MK-9(H4) and MK-9(H6). The phospholipid profile included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, an undefined aminophospholipid and two undefined phospholipids. DNA-DNA hybridization data in combination with differences in the biochemical and physiological properties, indicated that A251T should be classified as representing a novel species within the genus Actinocorallia, for which the name Actinocorallia populi sp. nov. is proposed, with A251T (=CGMCC 4.7421T=JCM 32178T) as the type strain.}, } @article {pmid29851376, year = {2018}, author = {Shin, SK and Kim, E and Yi, H}, title = {Gramella salexigens sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2381-2385}, doi = {10.1099/ijsem.0.002850}, pmid = {29851376}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, aerobic bacterial strain, designated LPB0144T was isolated from the seawater of South Sea, Korea. The 16S rRNA gene sequence was found to share the highest sequence similarity to Gramella sediminilitoris GHTF-27T (97.7 %) and the strain branched within the radiation of the genus Gramella in phylogenetic trees. Thus, the taxonomic position of the novel isolate was investigated using a polyphasic approach and complete genome sequencing. Strain LPB0144T has a circular chromosome of 2.98 Mb with DNA G+C content of 38.2 mol%. The genome includes 2604 protein-coding genes and three copies of rRNA operons. The detected respiratory quinone (MK-6) and the major polar lipid (phosphatidylethanolamine) resemble the chemotaxonomic profile of other Gramella species. The major cellular fatty acid profile (iso-C15 : 0, iso-C16 : 0, iso-C17 : 0 3-OH and anteiso-C15 : 0) is also within the range of Gramella, but detailed composition and amounts were found to be different from those of closely related neighbours. Many biochemical and physiological characteristics also distinguished the isolate from other species within the genus Gramella. On the basis of polyphasic taxonomic data obtained here, we propose strain LPB0144T as a novel Gramella species, for which the name Gramella salexigens sp. nov. is proposed. The type strain is LPB0144T (=KACC 18894T=JCM 31560T).}, } @article {pmid29851375, year = {2018}, author = {Wang, H and Zhang, X and Wang, S and Zhao, B and Lou, K and Xing, XH}, title = {Massilia violaceinigra sp. nov., a novel purple-pigmented bacterium isolated from glacier permafrost.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2271-2278}, doi = {10.1099/ijsem.0.002826}, pmid = {29851375}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Ice Cover/*microbiology ; Nucleic Acid Hybridization ; Oxalobacteraceae/*classification/genetics/isolation & purification ; Permafrost/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, motile and rod-shaped bacterium, designated strain B2T, which can synthesize purple pigments of violacein and dexyoviolacein, was isolated from Tianshan glacier in Xinjiang, China. Phylogenetic analysis based on 16S rRNA gene sequences indicated that it was grouped in the genus Massilia with Massilia glaciei B448-2T, Massilia eurypsychrophila B528-3T and Massilia psychrophila B1555-1T as its closest relatives (98.2, 97.9 and 97.0 % 16S rRNA gene sequence similarity, respectively). Genomic relatedness between strain B2T and its closest relatives was evaluated using average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity, with values of 77.93-85.08 %, 22.4-23.4 % and 71.54-72.99 %, respectively. Q-8 was the major ubiquinone. The major fatty acids (>5 %) of strain B2T were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C12 : 0 and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The major polar lipids included phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C content of strain B2T was 63.51 mol%. Based on genomic relatedness, physiological, biochemical and chemotaxonomic data, strain B2T (=CGMCC 1.6993T=DSM 19531T=KCTC 32446T) is considered to represent a novel species within the genus Massilia, for which the name Massilia violaceinigra sp. nov. is proposed.}, } @article {pmid29851374, year = {2018}, author = {Boden, R and Scott, KM}, title = {Evaluation of the genus Thiothrix Winogradsky 1888 (Approved Lists 1980) emend. Aruga et al. 2002: reclassification of Thiothrix disciformis to Thiolinea disciformis gen. nov., comb. nov., and of Thiothrix flexilis to Thiofilum flexile gen. nov., comb nov., with emended description of Thiothrix.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2226-2239}, doi = {10.1099/ijsem.0.002816}, pmid = {29851374}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Thiothrix/*classification ; }, abstract = {Thiothrix is the type genus of the Thiotrichaceae in the Thiotrichales of the Gammaproteobacteria, comprising nine species of sulfur-oxidising filamentous bacteria, which are variously autotrophic, heterotrophic or have mixed metabolic modes. Within the genus, four species show 16S rRNA gene identities lower the Yarza threshold for the rank of genus (94.5 %) - Thiothrix disciformis, Thiothrix flexilis, Thiothrix defluvii and Thiothrix eikelboomii - as they show no affiliation to extant genera, a polyphasic study was undertaken including biochemical, physiological and genomic properties and phylogeny based on the 16S rRNA gene (rrs), recombination protein A (RecA), polynucleotide nucleotidyltransferase (Pnp), translation initiation factor IF-2 (InfB), glyceraldehyde-3-phosphate dehydrogenase (GapA), glutaminyl-tRNA synthetase (GlnS), elongation factor EF-G (FusA) and concatamers of 53 ribosomal proteins encoded by rps, rpl and rpm operons, all of which support the reclassification of these species. We thus propose Thiolinea gen. nov. and Thiofilum gen. nov. for which the type species are Thiolinea disciformis gen. nov., comb. nov. and Thiofilum flexile gen. nov., comb. nov. We also propose that these genera are each circumscribed into novel families Thiolinaceae fam. nov. and Thiofilaceae fam. nov., and that Leucothrix and Cocleimonas are circumscribed into Leucotrichaceaefam. nov. and provide emended descriptions of Thiothrix and Thiotrichaceae.}, } @article {pmid29851373, year = {2018}, author = {Wang, J and Zhang, Q and Wang, Y and Qin, S and Luo, X}, title = {Streptomyces aqsuensis sp. nov., isolated from ditch sediment in Xinjiang, China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2178-2182}, doi = {10.1099/ijsem.0.002804}, pmid = {29851373}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptomyces/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinobacterium, designated TRM46399T, was isolated from ditch sediment in Xinjiang Province, Northwest China. Phylogenetic, physiological, chemotaxonomic and morphological analyses demonstrated that strain TRM46399T belonged to the genus Streptomyces. The strain was aerobic, Gram-stain-positive, had aerial mycelia that branched monopodially and formed chains of arthrospores. The spores were oval to cylindrical with smooth surfaces. The strain had an optimum NaCl concentration for growth of 5 % (w/v). The whole-cell sugar pattern of TRM46399T consisted of ribose, xylose, mannose and galactose. The predominant menaquinones were MK-9(H6), MK-9(H8) and MK-9(H10). The polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannosides. Major fatty acids were iso-C16 : 0 (47.8 %), iso-C14 : 0 (13.5 %), C16 : 0 (8.9 %), anteiso-C15 : 0 (8.4 %), anteiso-C17 : 0 (4.2 %) and C17 : 0cyclo (2.7 %). The G+C content of the genomic DNA was 68.7 mol%. Comparative 16S rRNA gene sequence analysis indicated that strain TRM46399T (KY688182) was phylogenetically most closely related to Streptomyces xinghaiensis S187T (99.13 % sequence similarity); however, DNA-DNA hybridization studies between stain TRM46399T and S. xinhaiensis S187T showed only 65.32 % relatedness. Based on the evidence from this polyphasic study, strain TRM46399T represents a novel species of the genus Streptomyces, for which the name Streptomyces aqsuensis sp. nov. is proposed. The type strain is TRM46399T (=KCTC 39610 T=CCTCC AA 2015009T).}, } @article {pmid29851081, year = {2018}, author = {Kristiansen, EB and Finkbeiner, SD and Hill, RI and Prusa, L and Mullen, SP}, title = {Testing the adaptive hypothesis of Batesian mimicry among hybridizing North American admiral butterflies.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13488}, pmid = {29851081}, issn = {1558-5646}, abstract = {Batesian mimicry is characterized by phenotypic convergence between an unpalatable model and a palatable mimic. However, because convergent evolution may arise via alternative evolutionary mechanisms, putative examples of Batesian mimicry must be rigorously tested. Here, we used artificial butterfly facsimiles (N = 4000) to test the prediction that (1) palatable Limenitis lorquini butterflies should experience reduced predation when in sympatry with their putative model, Adelpha californica, (2) protection from predation on L. lorquini should erode outside of the geographical range of the model, and (3) mimetic color pattern traits are more variable in allopatry, consistent with relaxed selection for mimicry. We find support for these predictions, implying that this convergence is the result of selection for Batesian mimicry. Additionally, we conducted mark-recapture studies to examine the effect of mimicry and found that mimics survive significantly longer at sites where the model is abundant. Finally, in contrast to theoretical predictions, we found evidence that the Batesian model (A. californica) is protected from predation outside of its geographic range. We discuss these results considering the ongoing hybridization between L. lorquini and its sister species, L. weidemeyerii, and growing evidence that selection for mimicry predictably leads to a reduction in gene flow between nascent species.}, } @article {pmid29850855, year = {2018}, author = {Terán, LC and Coeuret, G and Raya, R and Zagorec, M and Champomier-Vergès, MC and Chaillou, S}, title = {Phylogenomic Analysis of Lactobacillus curvatus Reveals Two Lineages Distinguished by Genes for Fermenting Plant-Derived Carbohydrates.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1516-1525}, pmid = {29850855}, issn = {1759-6653}, mesh = {Carbohydrates/*genetics ; Fermentation/*genetics ; Genome, Bacterial/genetics ; Genomics/methods ; Lactobacillus/*genetics ; Meat Products ; Multigene Family/genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Lactobacillus curvatus is a lactic acid bacterium encountered in many different types of fermented food (meat, seafood, vegetables, and cereals). Although this species plays an important role in the preservation of these foods, few attempts have been made to assess its genomic diversity. This study uses comparative analyses of 13 published genomes (complete or draft) to better understand the evolutionary processes acting on the genome of this species. Phylogenomic analysis, based on a coalescent model of evolution, revealed that the 6,742 sites of single nucleotide polymorphism within the L. curvatus core genome delineate two major groups, with lineage 1 represented by the newly sequenced strain FLEC03, and lineage 2 represented by the type-strain DSM20019. The two lineages could also be distinguished by the content of their accessory genome, which sheds light on a long-term evolutionary process of lineage-dependent genetic acquisition and the possibility of population structure. Interestingly, one clade from lineage 2 shared more accessory genes with strains of lineage 1 than with other strains of lineage 2, indicating recent convergence in carbohydrate catabolism. Both lineages had a wide repertoire of accessory genes involved in the fermentation of plant-derived carbohydrates that are released from polymers of α/β-glucans, α/β-fructans, and N-acetylglucosan. Other gene clusters were distributed among strains according to the type of food from which the strains were isolated. These results give new insight into the ecological niches in which L. curvatus may naturally thrive (such as silage or compost heaps) in addition to fermented food.}, } @article {pmid29850830, year = {2018}, author = {Wang, X and Zhou, T and Wunderlich, Z and Maurano, MT and DePace, AH and Nuzhdin, SV and Rohs, R}, title = {Analysis of Genetic Variation Indicates DNA Shape Involvement in Purifying Selection.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1958-1967}, pmid = {29850830}, issn = {1537-1719}, support = {R00 HD073191/HD/NICHD NIH HHS/United States ; R01 GM106056/GM/NIGMS NIH HHS/United States ; U01 GM103804/GM/NIGMS NIH HHS/United States ; }, abstract = {Noncoding DNA sequences, which play various roles in gene expression and regulation, are under evolutionary pressure. Gene regulation requires specific protein-DNA binding events, and our previous studies showed that both DNA sequence and shape readout are employed by transcription factors (TFs) to achieve DNA binding specificity. By investigating the shape-disrupting properties of single nucleotide polymorphisms (SNPs) in human regulatory regions, we established a link between disruptive local DNA shape changes and loss of specific TF binding. Furthermore, we described cases where disease-associated SNPs may alter TF binding through DNA shape changes. This link led us to hypothesize that local DNA shape within and around TF binding sites is under selection pressure. To verify this hypothesis, we analyzed SNP data derived from 216 natural strains of Drosophila melanogaster. Comparing SNPs located in functional and nonfunctional regions within experimentally validated cis-regulatory modules (CRMs) from D. melanogaster that are active in the blastoderm stage of development, we found that SNPs within functional regions tended to cause smaller DNA shape variations. Furthermore, SNPs with higher minor allele frequency were more likely to result in smaller DNA shape variations. The same analysis based on a large number of SNPs in putative CRMs of the D. melanogaster genome derived from DNase I accessibility data confirmed these observations. Taken together, our results indicate that common SNPs in functional regions tend to maintain DNA shape, whereas shape-disrupting SNPs are more likely to be eliminated through purifying selection.}, } @article {pmid29850825, year = {2018}, author = {Gallagher, AL and Miller, SR}, title = {Expression of Novel Gene Content Drives Adaptation to Low Iron in the Cyanobacterium Acaryochloris.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1484-1492}, pmid = {29850825}, issn = {1759-6653}, mesh = {Adaptation, Physiological/*genetics ; Cyanobacteria/*genetics ; DNA, Bacterial/genetics ; Evolution, Molecular ; Gene Dosage/genetics ; Gene Transfer, Horizontal/genetics ; Genes, Bacterial/*genetics ; Genes, Duplicate/genetics ; Genome, Bacterial/*genetics ; Iron/*metabolism ; }, abstract = {Variation in genome content is a potent mechanism of microbial adaptation. The genomes of members of the cyanobacterial genus Acaryochloris vary greatly in gene content as a consequence of the idiosyncratic retention of both recent gene duplicates and plasmid-encoded genes acquired by horizontal transfer. For example, the genome of Acaryochloris strain MBIC11017, which was isolated from an iron-limited environment, is enriched in duplicated and novel genes involved in iron assimilation. Here, we took an integrative approach to characterize the adaptation of Acaryochloris MBIC11017 to low environmental iron availability and the relative contributions of the expression of duplicated versus novel genes. We observed that Acaryochloris MBIC11017 grew faster and to a higher yield in the presence of nanomolar concentrations of iron than did a closely related strain. These differences were associated with both a higher rate of iron assimilation and a greater abundance of iron assimilation transcripts. However, recently duplicated genes contributed little to increased transcript dosage; rather, the maintenance of these duplicates in the MBIC11017 genome is likely due to the sharing of ancestral dosage by expression reduction. Instead, novel, horizontally transferred genes are responsible for the differences in transcript abundance. The study provides insights on the mechanisms of adaptive genome evolution and gene expression in Acaryochloris.}, } @article {pmid29850813, year = {2018}, author = {Lemopoulos, A and Uusi-Heikkilä, S and Huusko, A and Vasemägi, A and Vainikka, A}, title = {Comparison of Migratory and Resident Populations of Brown Trout Reveals Candidate Genes for Migration Tendency.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1493-1503}, pmid = {29850813}, issn = {1759-6653}, mesh = {Animal Migration/*physiology ; Animals ; Evolution, Molecular ; Fresh Water ; Osmoregulation/genetics ; Polymorphism, Single Nucleotide/genetics ; Salmonidae/genetics ; Seawater ; Trout/*genetics/*physiology ; }, abstract = {Candidate genes associated with migration have been identified in multiple taxa: including salmonids, many of whom perform migrations requiring a series of physiological changes associated with the freshwater-saltwater transition. We screened over 5,500 SNPs for signatures of selection related to migratory behavior of brown trout Salmo trutta by focusing on ten differentially migrating freshwater populations from two watersheds (the Koutajoki and the Oulujoki). We found eight outlier SNPs potentially associated with migratory versus resident life history using multiple (≥3) outlier detection approaches. Comparison of three migratory versus resident population pairs in the Koutajoki watershed revealed seven outlier SNPs, of which three mapped close to genes ZNF665-like, GRM4-like, and PCDH8-like that have been previously associated with migration and smoltification in salmonids. Two outlier SNPs mapped to genes involved in mucus secretion (ST3GAL1-like) and osmoregulation (C14orf37-like). The last two strongly supported outlier SNPs mapped to thermally induced genes (FNTA1-like, FAM134C-like). Within the Oulujoki, the only consistent outlier SNP mapped close to a gene (EZH2) that is associated with compensatory growth in fasted trout. Our results suggest that a relatively small yet common set of genes responsible for physiological functions associated with resident and migratory life histories is evolutionarily conserved.}, } @article {pmid29850809, year = {2018}, author = {Biscotti, MA and Adolfi, MC and Barucca, M and Forconi, M and Pallavicini, A and Gerdol, M and Canapa, A and Schartl, M}, title = {A Comparative View on Sex Differentiation and Gametogenesis Genes in Lungfish and Coelacanths.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1430-1444}, pmid = {29850809}, issn = {1759-6653}, mesh = {Animals ; Chordata/*genetics ; Evolution, Molecular ; Fishes/*genetics ; Gametogenesis/*genetics ; Male ; Phylogeny ; Reproduction/genetics ; Sex Differentiation/*genetics ; }, abstract = {Gonadal sex differentiation and reproduction are the keys to the perpetuation of favorable gene combinations and positively selected traits. In vertebrates, several gonad development features that differentiate tetrapods and fishes are likely to be, at least in part, related to the water-to-land transition. The collection of information from basal sarcopterygians, coelacanths, and lungfishes, is crucial to improve our understanding of the molecular evolution of pathways involved in reproductive functions, since these organisms are generally regarded as "living fossils" and as the direct ancestors of tetrapods. Here, we report for the first time the characterization of >50 genes related to sex differentiation and gametogenesis in Latimeria menadoensis and Protopterus annectens. Although the expression profiles of most genes is consistent with the intermediate position of basal sarcopterygians between actinopterygian fish and tetrapods, their phylogenetic placement and presence/absence patterns often reveal a closer affinity to the tetrapod orthologs. On the other hand, particular genes, for example, the male gonad factor gsdf (Gonadal Soma-Derived Factor), provide examples of ancestral traits shared with actinopterygians, which disappeared in the tetrapod lineage.}, } @article {pmid29850801, year = {2018}, author = {Nishiyama, E and Ohshima, K}, title = {Cross-Kingdom Commonality of a Novel Insertion Signature of RTE-Related Short Retroposons.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1471-1483}, pmid = {29850801}, issn = {1759-6653}, mesh = {Animals ; DNA Transposable Elements/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome, Plant/genetics ; Lizards/genetics ; Long Interspersed Nucleotide Elements/genetics ; Magnoliopsida/genetics ; Mammals/genetics ; Microsatellite Repeats/genetics ; Mutagenesis, Insertional/methods ; Phylogeny ; Retroelements/*genetics ; Reverse Transcription/genetics ; Short Interspersed Nucleotide Elements/genetics ; }, abstract = {In multicellular organisms, such as vertebrates and flowering plants, horizontal transfer (HT) of genetic information is thought to be a rare event. However, recent findings unveiled unexpectedly frequent HT of RTE-clade LINEs. To elucidate the molecular footprints of the genomic integration machinery of RTE-related retroposons, the sequence patterns surrounding the insertion sites of plant Au-like SINE families were analyzed in the genomes of a wide variety of flowering plants. A novel and remarkable finding regarding target site duplications (TSDs) for SINEs was they start with thymine approximately one helical pitch (ten nucleotides) downstream of a thymine stretch. This TSD pattern was found in RTE-clade LINEs, which share the 3'-end sequence of these SINEs, in the genome of leguminous plants. These results demonstrably show that Au-like SINEs were mobilized by the enzymatic machinery of RTE-clade LINEs. Further, we discovered the same TSD pattern in animal SINEs from lizard and mammals, in which the RTE-clade LINEs sharing the 3'-end sequence with these animal SINEs showed a distinct TSD pattern. Moreover, a significant correlation was observed between the first nucleotide of TSDs and microsatellite-like sequences found at the 3'-ends of SINEs and LINEs. We propose that RTE-encoded protein could preferentially bind to a DNA region that contains a thymine stretch to cleave a phosphodiester bond downstream of the stretch. Further, determination of cleavage sites and/or efficiency of primer sites for reverse transcription may depend on microsatellite-like repeats in the RNA template. Such a unique mechanism may have enabled retroposons to successfully expand in frontier genomes after HT.}, } @article {pmid29850800, year = {2018}, author = {Guillory, WX and Onyshchenko, A and Ruck, EC and Parks, M and Nakov, T and Wickett, NJ and Alverson, AJ}, title = {Recurrent Loss, Horizontal Transfer, and the Obscure Origins of Mitochondrial Introns in Diatoms (Bacillariophyta).}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1504-1515}, pmid = {29850800}, issn = {1759-6653}, mesh = {DNA, Mitochondrial/genetics ; Diatoms/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; Genome, Mitochondrial/*genetics ; Introns/*genetics ; Mitochondria/*genetics ; Phylogeny ; Sequence Analysis, DNA/methods ; }, abstract = {We sequenced mitochondrial genomes from five diverse diatoms (Toxarium undulatum, Psammoneis japonica, Eunotia naegelii, Cylindrotheca closterium, and Nitzschia sp.), chosen to fill important phylogenetic gaps and help us characterize broadscale patterns of mitochondrial genome evolution in diatoms. Although gene content was strongly conserved, intron content varied widely across species. The vast majority of introns were of group II type and were located in the cox1 or rnl genes. Although recurrent intron loss appears to be the principal underlying cause of the sporadic distributions of mitochondrial introns across diatoms, phylogenetic analyses showed that intron distributions superficially consistent with a recurrent-loss model were sometimes more complicated, implicating horizontal transfer as a likely mechanism of intron acquisition as well. It was not clear, however, whether diatoms were the donors or recipients of horizontally transferred introns, highlighting a general challenge in resolving the evolutionary histories of many diatom mitochondrial introns. Although some of these histories may become clearer as more genomes are sampled, high rates of intron loss suggest that the origins of many diatom mitochondrial introns are likely to remain unclear.}, } @article {pmid29850797, year = {2018}, author = {Manthey, JD and Moyle, RG and Boissinot, S}, title = {Multiple and Independent Phases of Transposable Element Amplification in the Genomes of Piciformes (Woodpeckers and Allies).}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1445-1456}, pmid = {29850797}, issn = {1759-6653}, mesh = {Animals ; Birds/*genetics ; DNA Transposable Elements/*genetics ; Evolution, Molecular ; Genome/*genetics ; Genome Size/genetics ; Genomics/methods ; Phylogeny ; Polymorphism, Genetic/genetics ; Retroelements/genetics ; }, abstract = {The small and conserved genomes of birds are likely a result of flight-related metabolic constraints. Recombination-driven deletions and minimal transposable element (TE) expansions have led to continually shrinking genomes during evolution of many lineages of volant birds. Despite constraints of genome size in birds, we identified multiple waves of amplification of TEs in Piciformes (woodpeckers, honeyguides, toucans, and barbets). Relative to other bird species' genomic TE abundance (< 10% of genome), we found ∼17-30% TE content in multiple clades within Piciformes. Several families of the retrotransposon superfamily chicken repeat 1 (CR1) expanded in at least three different waves of activity. The most recent CR1 expansions (∼4-7% of genome) preceded bursts of diversification in the woodpecker clade and in the American barbets + toucans clade. Additionally, we identified several thousand polymorphic CR1 insertions (hundreds per individual) in three closely related woodpecker species. Woodpecker CR1 insertion polymorphisms are maintained at lower frequencies than single nucleotide polymorphisms indicating that purifying selection is acting against additional CR1 copies and that these elements impose a fitness cost on their host. These findings provide evidence of large scale and ongoing TE activity in avian genomes despite continual constraint on genome size.}, } @article {pmid29850794, year = {2018}, author = {Barrett, CF and Kennedy, AH}, title = {Plastid Genome Degradation in the Endangered, Mycoheterotrophic, North American Orchid Hexalectris warnockii.}, journal = {Genome biology and evolution}, volume = {10}, number = {7}, pages = {1657-1662}, doi = {10.1093/gbe/evy107}, pmid = {29850794}, issn = {1759-6653}, mesh = {Endangered Species ; Evolution, Molecular ; *Genes, Plant ; *Genome, Plastid ; Heterotrophic Processes ; North America ; Orchidaceae/*genetics ; Plant Proteins/genetics ; Pseudogenes ; }, abstract = {Heterotrophic plants provide evolutionarily independent, natural experiments in the genomic consequences of radically altered nutritional regimes. Here, we have sequenced and annotated the plastid genome of the endangered mycoheterotrophic orchid Hexalectris warnockii. This orchid bears a plastid genome that is ∼80% the total length of the leafy, photosynthetic Phalaenopsis, and contains just over half the number of putatively functional genes of the latter. The plastid genome of H. warnockii bears pseudogenes and has experienced losses of genes encoding proteins directly (e.g., psa/psb, rbcL) and indirectly involved in photosynthesis (atp genes), suggesting it has progressed beyond the initial stages of plastome degradation, based on previous models of plastid genome evolution. Several dispersed and tandem repeats were detected, that are potentially useful as conservation genetic markers. In addition, a 29-kb inversion and a significant contraction of the inverted repeat boundaries are observed in this plastome. The Hexalectris warnockii plastid genome adds to a growing body of data useful in refining evolutionary models in parasites, and provides a resource for conservation studies in these endangered orchids.}, } @article {pmid29850789, year = {2018}, author = {Fouché, S and Plissonneau, C and McDonald, BA and Croll, D}, title = {Meiosis Leads to Pervasive Copy-Number Variation and Distorted Inheritance of Accessory Chromosomes of the Wheat Pathogen Zymoseptoria tritici.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1416-1429}, pmid = {29850789}, issn = {1759-6653}, mesh = {Ascomycota/*genetics ; Chromosome Aberrations ; Chromosomes, Fungal/*genetics ; DNA Copy Number Variations/*genetics ; Gene Rearrangement/genetics ; Genetic Markers/genetics ; Meiosis/*genetics ; Triticum/*microbiology ; }, abstract = {Meiosis is one of the most conserved molecular processes in eukaryotes. The fidelity of pairing and segregation of homologous chromosomes has a major impact on the proper transmission of genetic information. Aberrant chromosomal transmission can have major phenotypic consequences, yet the mechanisms are poorly understood. Fungi are excellent models to investigate processes of chromosomal transmission, because many species have highly polymorphic genomes that include accessory chromosomes. Inheritance of accessory chromosomes is often unstable and chromosomal losses have little impact on fitness. We analyzed chromosomal inheritance in 477 progeny coming from two crosses of the fungal wheat pathogen Zymoseptoria tritici. For this, we developed a high-throughput screening method based on restriction site-associated DNA sequencing that generated dense coverage of genetic markers along each chromosome. We identified rare instances of chromosomal duplications (disomy) in core chromosomes. Accessory chromosomes showed high overall frequencies of disomy. Chromosomal rearrangements were found exclusively on accessory chromosomes and were more frequent than disomy. Accessory chromosomes present in only one of the parents in an analyzed cross were inherited at significantly higher rates than the expected 1:1 segregation ratio. Both the chromosome and the parental background had significant impacts on the rates of disomy, losses, rearrangements, and distorted inheritance. We found that chromosomes with higher sequence similarity and lower repeat content were inherited more faithfully. The large number of rearranged progeny chromosomes identified in this species will enable detailed analyses of the mechanisms underlying chromosomal rearrangement.}, } @article {pmid29850787, year = {2018}, author = {Manee, MM and Jackson, J and Bergman, CM}, title = {Conserved Noncoding Elements Influence the Transposable Element Landscape in Drosophila.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1533-1545}, pmid = {29850787}, issn = {1759-6653}, mesh = {Animals ; Conserved Sequence/*genetics ; DNA Transposable Elements/*genetics ; Drosophila/*genetics ; Drosophila melanogaster/*genetics ; Eukaryota/genetics ; Exons/genetics ; Gene Frequency/genetics ; Genome, Insect/*genetics ; Mutation/genetics ; RNA, Untranslated/*genetics ; Selection, Genetic/genetics ; }, abstract = {Highly conserved noncoding elements (CNEs) constitute a significant proportion of the genomes of multicellular eukaryotes. The function of most CNEs remains elusive, but growing evidence indicates they are under some form of purifying selection. Noncoding regions in many species also harbor large numbers of transposable element (TE) insertions, which are typically lineage specific and depleted in exons because of their deleterious effects on gene function or expression. However, it is currently unknown whether the landscape of TE insertions in noncoding regions is random or influenced by purifying selection on CNEs. Here, we combine comparative and population genomic data in Drosophila melanogaster to show that the abundance of TE insertions in intronic and intergenic CNEs is reduced relative to random expectation, supporting the idea that selective constraints on CNEs eliminate a proportion of TE insertions in noncoding regions. However, we find no evidence for differences in the allele frequency spectra for polymorphic TE insertions in CNEs versus those in unconstrained spacer regions, suggesting that the distribution of fitness effects acting on observable TE insertions is similar across different functional compartments in noncoding DNA. Our results provide evidence that selective constraints on CNEs contribute to shaping the landscape of TE insertion in eukaryotic genomes, and provide further evidence that CNEs are indeed functionally constrained and not simply mutational cold spots.}, } @article {pmid29849164, year = {2018}, author = {}, title = {Bear hunt, right-to-try law and dark-matter disappointment.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {616-617}, doi = {10.1038/d41586-018-05257-z}, pmid = {29849164}, issn = {1476-4687}, } @article {pmid29849163, year = {2018}, author = {Tollefson, J}, title = {Innovative zero-emissions power plant begins battery of tests.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {622-623}, doi = {10.1038/d41586-018-05247-1}, pmid = {29849163}, issn = {1476-4687}, } @article {pmid29849162, year = {2018}, author = {}, title = {Police use a computer to expose false testimony.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {612}, doi = {10.1038/d41586-018-05285-9}, pmid = {29849162}, issn = {1476-4687}, mesh = {*Computers ; Law Enforcement ; *Police ; *Truth Disclosure ; }, } @article {pmid29849161, year = {2018}, author = {O'Meara, S}, title = {China's Zhejiang province is open for science business.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S51-S52}, doi = {10.1038/d41586-018-05265-z}, pmid = {29849161}, issn = {1476-4687}, mesh = {Animals ; China ; *Internationality ; Personnel Selection ; Science/*economics/*organization & administration/trends ; Universities/organization & administration/standards/trends ; Workforce ; }, } @article {pmid29849160, year = {2018}, author = {Fleming, N}, title = {How artificial intelligence is changing drug discovery.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S55-S57}, doi = {10.1038/d41586-018-05267-x}, pmid = {29849160}, issn = {1476-4687}, mesh = {Algorithms ; Amyotrophic Lateral Sclerosis/drug therapy ; Animals ; *Artificial Intelligence ; Automation/methods ; Drug Discovery/economics/education/*methods/trends ; Drug Industry/economics/methods/trends ; Efficiency, Organizational ; Humans ; Machine Learning ; Mice ; Neoplasms/drug therapy/metabolism ; Pattern Recognition, Automated/methods/trends ; Precision Medicine/methods/trends ; Robotics/economics/methods/trends ; }, } @article {pmid29849159, year = {2018}, author = {Qualkenbush, L}, title = {Cooperate to stop misconduct.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {637}, doi = {10.1038/d41586-018-05290-y}, pmid = {29849159}, issn = {1476-4687}, mesh = {Academies and Institutes/*ethics/legislation & jurisprudence/*organization & administration ; Ethics, Research ; Periodicals as Topic/*ethics ; Research/legislation & jurisprudence/*standards ; Retraction of Publication as Topic ; Scientific Misconduct/ethics/*legislation & jurisprudence ; }, } @article {pmid29849158, year = {2018}, author = {Acevedo-Rocha, CG}, title = {Microbes set to alter the economy.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {637}, doi = {10.1038/d41586-018-05291-x}, pmid = {29849158}, issn = {1476-4687}, mesh = {Biotechnology/*trends ; Gene Editing/*trends ; Microbiology/trends ; }, } @article {pmid29849157, year = {2018}, author = {Slota, M and Keerthi, A and Myers, WK and Tretyakov, E and Baumgarten, M and Ardavan, A and Sadeghi, H and Lambert, CJ and Narita, A and Müllen, K and Bogani, L}, title = {Magnetic edge states and coherent manipulation of graphene nanoribbons.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {691-695}, doi = {10.1038/s41586-018-0154-7}, pmid = {29849157}, issn = {1476-4687}, abstract = {Graphene, a single-layer network of carbon atoms, has outstanding electrical and mechanical properties 1 . Graphene ribbons with nanometre-scale widths2,3 (nanoribbons) should exhibit half-metallicity 4 and quantum confinement. Magnetic edges in graphene nanoribbons5,6 have been studied extensively from a theoretical standpoint because their coherent manipulation would be a milestone for spintronic 7 and quantum computing devices 8 . However, experimental investigations have been hampered because nanoribbon edges cannot be produced with atomic precision and the graphene terminations that have been proposed are chemically unstable 9 . Here we address both of these problems, by using molecular graphene nanoribbons functionalized with stable spin-bearing radical groups. We observe the predicted delocalized magnetic edge states and test theoretical models of the spin dynamics and spin-environment interactions. Comparison with a non-graphitized reference material enables us to clearly identify the characteristic behaviour of the radical-functionalized graphene nanoribbons. We quantify the parameters of spin-orbit coupling, define the interaction patterns and determine the spin decoherence channels. Even without any optimization, the spin coherence time is in the range of microseconds at room temperature, and we perform quantum inversion operations between edge and radical spins. Our approach provides a way of testing the theory of magnetism in graphene nanoribbons experimentally. The coherence times that we observe open up encouraging prospects for the use of magnetic nanoribbons in quantum spintronic devices.}, } @article {pmid29849156, year = {2018}, author = {Simões, TR and Caldwell, MW and Tałanda, M and Bernardi, M and Palci, A and Vernygora, O and Bernardini, F and Mancini, L and Nydam, RL}, title = {The origin of squamates revealed by a Middle Triassic lizard from the Italian Alps.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {706-709}, doi = {10.1038/s41586-018-0093-3}, pmid = {29849156}, issn = {1476-4687}, mesh = {Altitude ; Animals ; Bayes Theorem ; *Fossils ; Italy ; Lizards/anatomy & histology/*classification ; Phylogeny ; }, abstract = {Modern squamates (lizards, snakes and amphisbaenians) are the world's most diverse group of tetrapods along with birds 1 and have a long evolutionary history, with the oldest known fossils dating from the Middle Jurassic period-168 million years ago2-4. The evolutionary origin of squamates is contentious because of several issues: (1) a fossil gap of approximately 70 million years exists between the oldest known fossils and their estimated origin5-7; (2) limited sampling of squamates in reptile phylogenies; and (3) conflicts between morphological and molecular hypotheses regarding the origin of crown squamates6,8,9. Here we shed light on these problems by using high-resolution microfocus X-ray computed tomography data from the articulated fossil reptile Megachirella wachtleri (Middle Triassic period, Italian Alps 10). We also present a phylogenetic dataset, combining fossils and extant taxa, and morphological and molecular data. We analysed this dataset under different optimality criteria to assess diapsid reptile relationships and the origins of squamates. Our results re-shape the diapsid phylogeny and present evidence that M. wachtleri is the oldest known stem squamate. Megachirella is 75 million years older than the previously known oldest squamate fossils, partially filling the fossil gap in the origin of lizards, and indicates a more gradual acquisition of squamatan features in diapsid evolution than previously thought. For the first time, to our knowledge, morphological and molecular data are in agreement regarding early squamate evolution, with geckoes-and not iguanians-as the earliest crown clade squamates. Divergence time estimates using relaxed combined morphological and molecular clocks show that lepidosaurs and most other diapsids originated before the Permian/Triassic extinction event, indicating that the Triassic was a period of radiation, not origin, for several diapsid lineages.}, } @article {pmid29849155, year = {2018}, author = {Sparrow, C and Martín-López, E and Maraviglia, N and Neville, A and Harrold, C and Carolan, J and Joglekar, YN and Hashimoto, T and Matsuda, N and O'Brien, JL and Tew, DP and Laing, A}, title = {Simulating the vibrational quantum dynamics of molecules using photonics.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {660-667}, doi = {10.1038/s41586-018-0152-9}, pmid = {29849155}, issn = {1476-4687}, abstract = {Advances in control techniques for vibrational quantum states in molecules present new challenges for modelling such systems, which could be amenable to quantum simulation methods. Here, by exploiting a natural mapping between vibrations in molecules and photons in waveguides, we demonstrate a reprogrammable photonic chip as a versatile simulation platform for a range of quantum dynamic behaviour in different molecules. We begin by simulating the time evolution of vibrational excitations in the harmonic approximation for several four-atom molecules, including H2CS, SO3, HNCO, HFHF, N4 and P4. We then simulate coherent and dephased energy transport in the simplest model of the peptide bond in proteins-N-methylacetamide-and simulate thermal relaxation and the effect of anharmonicities in H2O. Finally, we use multi-photon statistics with a feedback control algorithm to iteratively identify quantum states that increase a particular dissociation pathway of NH3. These methods point to powerful new simulation tools for molecular quantum dynamics and the field of femtochemistry.}, } @article {pmid29849154, year = {2018}, author = {Wong, FK and Bercsenyi, K and Sreenivasan, V and Portalés, A and Fernández-Otero, M and Marín, O}, title = {Pyramidal cell regulation of interneuron survival sculpts cortical networks.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {668-673}, pmid = {29849154}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; 103714MA//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Count ; Cell Death ; Cell Survival ; Cerebral Cortex/*cytology/*physiology ; Female ; Interneurons/*cytology/physiology ; Male ; Mice ; *Neural Pathways ; PTEN Phosphohydrolase/antagonists & inhibitors/metabolism ; Pyramidal Cells/*physiology ; }, abstract = {Complex neuronal circuitries such as those found in the mammalian cerebral cortex have evolved as balanced networks of excitatory and inhibitory neurons. Although the establishment of appropriate numbers of these cells is essential for brain function and behaviour, our understanding of this fundamental process is limited. Here we show that the survival of interneurons in mice depends on the activity of pyramidal cells in a critical window of postnatal development, during which excitatory synaptic input to individual interneurons predicts their survival or death. Pyramidal cells regulate interneuron survival through the negative modulation of PTEN signalling, which effectively drives interneuron cell death during this period. Our findings indicate that activity-dependent mechanisms dynamically adjust the number of inhibitory cells in nascent local cortical circuits, ultimately establishing the appropriate proportions of excitatory and inhibitory neurons in the cerebral cortex.}, } @article {pmid29849153, year = {2018}, author = {Muñoz, JB and Loeb, A}, title = {A small amount of mini-charged dark matter could cool the baryons in the early Universe.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {684-686}, doi = {10.1038/s41586-018-0151-x}, pmid = {29849153}, issn = {1476-4687}, abstract = {The dynamics of our Universe is strongly influenced by pervasive-albeit elusive-dark matter, with a total mass about five times the mass of all the baryons1,2. Despite this, its origin and composition remain a mystery. All evidence for dark matter relies on its gravitational pull on baryons, and thus such evidence does not require any non-gravitational coupling between baryons and dark matter. Nonetheless, some small coupling would explain the comparable cosmic abundances of dark matter and baryons 3 , as well as solving structure-formation puzzles in the pure cold-dark-matter models 4 . A vast array of observations has been unable to find conclusive evidence for any non-gravitational interactions of baryons with dark matter5-9. Recent observations by the EDGES collaboration, however, suggest that during the cosmic dawn, roughly 200 million years after the Big Bang, the baryonic temperature was half of its expected value 10 . This observation is difficult to reconcile with the standard cosmological model but could be explained if baryons are cooled down by interactions with dark matter, as expected if their interaction rate grows steeply at low velocities 11 . Here we report that if a small fraction-less than one per cent-of the dark matter has a mini-charge, a million times smaller than the charge on the electron, and a mass in the range of 1-100 times the electron mass, then the data 10 from the EDGES experiment can be explained while remaining consistent with all other observations. We also show that the entirety of the dark matter cannot have a mini-charge.}, } @article {pmid29849151, year = {2018}, author = {Du, X and Wen, J and Wang, Y and Karmaus, PWF and Khatamian, A and Tan, H and Li, Y and Guy, C and Nguyen, TM and Dhungana, Y and Neale, G and Peng, J and Yu, J and Chi, H}, title = {Hippo/Mst signalling couples metabolic state and immune function of CD8α+ dendritic cells.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {141-145}, pmid = {29849151}, issn = {1476-4687}, support = {CA221290/NH/NIH HHS/United States ; NS064599/NH/NIH HHS/United States ; AG047928/NH/NIH HHS/United States ; AI101407/NH/NIH HHS/United States ; R01 NS064599/NS/NINDS NIH HHS/United States ; R01 AI105887/AI/NIAID NIH HHS/United States ; AI105887/NH/NIH HHS/United States ; R01 CA176624/CA/NCI NIH HHS/United States ; R01 CA221290/CA/NCI NIH HHS/United States ; CA176624/NH/NIH HHS/United States ; R01 AI101407/AI/NIAID NIH HHS/United States ; R01 AG047928/AG/NIA NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; CD8 Antigens/immunology/*metabolism ; CD8-Positive T-Lymphocytes/cytology/immunology ; Cross-Priming/immunology ; Dendritic Cells/cytology/*immunology/*metabolism ; Homeostasis ; Interleukin-12/immunology/metabolism ; Mice ; Mice, Inbred C57BL ; NF-kappa B/metabolism ; Protein-Serine-Threonine Kinases/deficiency/genetics/*metabolism ; *Signal Transduction ; Tumor Suppressor Proteins ; }, abstract = {Dendritic cells orchestrate the crosstalk between innate and adaptive immunity. CD8α+ dendritic cells present antigens to CD8+ T cells and elicit cytotoxic T cell responses to viruses, bacteria and tumours 1 . Although lineage-specific transcriptional regulators of CD8α+ dendritic cell development have been identified 2 , the molecular pathways that selectively orchestrate CD8α+ dendritic cell function remain elusive. Moreover, metabolic reprogramming is important for dendritic cell development and activation3,4, but metabolic dependence and regulation of dendritic cell subsets are largely uncharacterized. Here we use a data-driven systems biology algorithm (NetBID) to identify a role of the Hippo pathway kinases Mst1 and Mst2 (Mst1/2) in selectively programming CD8α+ dendritic cell function and metabolism. Our NetBID analysis reveals a marked enrichment of the activities of Hippo pathway kinases in CD8α+ dendritic cells relative to CD8α- dendritic cells. Dendritic cell-specific deletion of Mst1/2-but not Lats1 and Lats2 (Lats1/2) or Yap and Taz (Yap/Taz), which mediate canonical Hippo signalling-disrupts homeostasis and function of CD8+ T cells and anti-tumour immunity. Mst1/2-deficient CD8α+ dendritic cells are impaired in presentation of extracellular proteins and cognate peptides to prime CD8+ T cells, while CD8α- dendritic cells that lack Mst1/2 have largely normal function. Mechanistically, compared to CD8α- dendritic cells, CD8α+ dendritic cells exhibit much stronger oxidative metabolism and critically depend on Mst1/2 signalling to maintain bioenergetic activities and mitochondrial dynamics for their functional capacities. Further, selective expression of IL-12 by CD8α+ dendritic cells depends on Mst1/2 and the crosstalk with non-canonical NF-κB signalling. Our findings identify Mst1/2 as selective drivers of CD8α+ dendritic cell function by integrating metabolic activity and cytokine signalling, and highlight that the interplay between immune signalling and metabolic reprogramming underlies the unique functions of dendritic cell subsets.}, } @article {pmid29849150, year = {2018}, author = {Chang, CC and Nicholson, AN and Rinaldi, E and Berkowitz, E and Garron, N and Brantley, DA and Monge-Camacho, H and Monahan, CJ and Bouchard, C and Clark, MA and Joó, B and Kurth, T and Orginos, K and Vranas, P and Walker-Loud, A}, title = {A per-cent-level determination of the nucleon axial coupling from quantum chromodynamics.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {91-94}, doi = {10.1038/s41586-018-0161-8}, pmid = {29849150}, issn = {1476-4687}, abstract = {The axial coupling of the nucleon, gA, is the strength of its coupling to the weak axial current of the standard model of particle physics, in much the same way as the electric charge is the strength of the coupling to the electromagnetic current. This axial coupling dictates the rate at which neutrons decay to protons, the strength of the attractive long-range force between nucleons and other features of nuclear physics. Precision tests of the standard model in nuclear environments require a quantitative understanding of nuclear physics that is rooted in quantum chromodynamics, a pillar of the standard model. The importance of gA makes it a benchmark quantity to determine theoretically-a difficult task because quantum chromodynamics is non-perturbative, precluding known analytical methods. Lattice quantum chromodynamics provides a rigorous, non-perturbative definition of quantum chromodynamics that can be implemented numerically. It has been estimated that a precision of two per cent would be possible by 2020 if two challenges are overcome1,2: contamination of gA from excited states must be controlled in the calculations and statistical precision must be improved markedly2-10. Here we use an unconventional method 11 inspired by the Feynman-Hellmann theorem that overcomes these challenges. We calculate a gA value of 1.271 ± 0.013, which has a precision of about one per cent.}, } @article {pmid29849149, year = {2018}, author = {Fernández, ÁF and Sebti, S and Wei, Y and Zou, Z and Shi, M and McMillan, KL and He, C and Ting, T and Liu, Y and Chiang, WC and Marciano, DK and Schiattarella, GG and Bhagat, G and Moe, OW and Hu, MC and Levine, B}, title = {Disruption of the beclin 1-BCL2 autophagy regulatory complex promotes longevity in mice.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {136-140}, pmid = {29849149}, issn = {1476-4687}, support = {R00 DK094980/DK/NIDDK NIH HHS/United States ; R01 DK091392/DK/NIDDK NIH HHS/United States ; R01 CA109618/CA/NCI NIH HHS/United States ; R01 DK113170/DK/NIDDK NIH HHS/United States ; R01 DK092461/DK/NIDDK NIH HHS/United States ; U19 AI109725/AI/NIAID NIH HHS/United States ; }, mesh = {Aging/genetics/*physiology ; Animals ; Autophagosomes/metabolism ; Autophagy/*physiology ; Beclin-1/genetics/*metabolism ; Cells, Cultured ; Female ; Fibroblasts/cytology ; Gene Knock-In Techniques ; Glucuronidase/deficiency/genetics ; HeLa Cells ; Health ; Humans ; Longevity/genetics/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mutation ; Proto-Oncogene Proteins c-bcl-2/*metabolism ; }, abstract = {Autophagy increases the lifespan of model organisms; however, its role in promoting mammalian longevity is less well-established1,2. Here we report lifespan and healthspan extension in a mouse model with increased basal autophagy. To determine the effects of constitutively increased autophagy on mammalian health, we generated targeted mutant mice with a Phe121Ala mutation in beclin 1 (Becn1F121A/F121A) that decreases its interaction with the negative regulator BCL2. We demonstrate that the interaction between beclin 1 and BCL2 is disrupted in several tissues in Becn1 F121A/F121A knock-in mice in association with higher levels of basal autophagic flux. Compared to wild-type littermates, the lifespan of both male and female knock-in mice is significantly increased. The healthspan of the knock-in mice also improves, as phenotypes such as age-related renal and cardiac pathological changes and spontaneous tumorigenesis are diminished. Moreover, mice deficient in the anti-ageing protein klotho 3 have increased beclin 1 and BCL2 interaction and decreased autophagy. These phenotypes, along with premature lethality and infertility, are rescued by the beclin 1(F121A) mutation. Together, our data demonstrate that disruption of the beclin 1-BCL2 complex is an effective mechanism to increase autophagy, prevent premature ageing, improve healthspan and promote longevity in mammals.}, } @article {pmid29849148, year = {2018}, author = {Wang, L and Gillis-Smith, S and Peng, Y and Zhang, J and Chen, X and Salzman, CD and Ryba, NJP and Zuker, CS}, title = {The coding of valence and identity in the mammalian taste system.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {127-131}, pmid = {29849148}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; P30 DK026687/DK/NIDDK NIH HHS/United States ; R01 DA035025/DA/NIDA NIH HHS/United States ; R01 MH082017/MH/NIMH NIH HHS/United States ; }, mesh = {Amygdala/*cytology/drug effects/*physiology ; Animals ; Appetitive Behavior/drug effects/*physiology ; Avoidance Learning/drug effects/*physiology ; Clozapine/analogs & derivatives/pharmacology ; Discrimination (Psychology)/drug effects/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Models, Neurological ; Neurons/drug effects/physiology ; Taste/drug effects/*physiology ; Water/pharmacology ; }, abstract = {The ability of the taste system to identify a tastant (what it tastes like) enables animals to recognize and discriminate between the different basic taste qualities1,2. The valence of a tastant (whether it is appetitive or aversive) specifies its hedonic value and elicits the execution of selective behaviours. Here we examine how sweet and bitter are afforded valence versus identity in mice. We show that neurons in the sweet-responsive and bitter-responsive cortex project to topographically distinct areas of the amygdala, with strong segregation of neural projections conveying appetitive versus aversive taste signals. By manipulating selective taste inputs to the amygdala, we show that it is possible to impose positive or negative valence on a neutral water stimulus, and even to reverse the hedonic value of a sweet or bitter tastant. Remarkably, mice with silenced neurons in the amygdala no longer exhibit behaviour that reflects the valence associated with direct stimulation of the taste cortex, or with delivery of sweet and bitter chemicals. Nonetheless, these mice can still identify and discriminate between tastants, just as wild-type controls do. These results help to explain how the taste system generates stereotypic and predetermined attractive and aversive taste behaviours, and support the existence of distinct neural substrates for the discrimination of taste identity and the assignment of valence.}, } @article {pmid29849147, year = {2018}, author = {Bellono, NW and Leitch, DB and Julius, D}, title = {Molecular tuning of electroreception in sharks and skates.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {122-126}, pmid = {29849147}, issn = {1476-4687}, support = {R35 NS105038/NS/NINDS NIH HHS/United States ; R01 NS055299/NS/NINDS NIH HHS/United States ; T32 HL007731/HL/NHLBI NIH HHS/United States ; K99 DC016658/DC/NIDCD NIH HHS/United States ; K99 DK115879/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Electric Conductivity ; Electric Organ/cytology/*physiology ; Female ; Humans ; Kinetics ; Male ; Potassium/metabolism ; Sharks/*physiology ; Skates (Fish)/*physiology ; }, abstract = {Ancient cartilaginous vertebrates, such as sharks, skates and rays, possess specialized electrosensory organs that detect weak electric fields and relay this information to the central nervous system1-4. Sharks exploit this sensory modality for predation, whereas skates may also use it to detect signals from conspecifics 5 . Here we analyse shark and skate electrosensory cells to determine whether discrete physiological properties could contribute to behaviourally relevant sensory tuning. We show that sharks and skates use a similar low threshold voltage-gated calcium channel to initiate cellular activity but use distinct potassium channels to modulate this activity. Electrosensory cells from sharks express specially adapted voltage-gated potassium channels that support large, repetitive membrane voltage spikes capable of driving near-maximal vesicular release from elaborate ribbon synapses. By contrast, skates use a calcium-activated potassium channel to produce small, tunable membrane voltage oscillations that elicit stimulus-dependent vesicular release. We propose that these sensory adaptations support amplified indiscriminate signal detection in sharks compared with selective frequency detection in skates, potentially reflecting the electroreceptive requirements of these elasmobranch species. Our findings demonstrate how sensory systems adapt to suit the lifestyle or environmental niche of an animal through discrete molecular and biophysical modifications.}, } @article {pmid29849146, year = {2018}, author = {Lu, H and Yu, D and Hansen, AS and Ganguly, S and Liu, R and Heckert, A and Darzacq, X and Zhou, Q}, title = {Phase-separation mechanism for C-terminal hyperphosphorylation of RNA polymerase II.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {318-323}, doi = {10.1038/s41586-018-0174-3}, pmid = {29849146}, issn = {1476-4687}, support = {R01 AI041757/AI/NIAID NIH HHS/United States ; }, mesh = {Cyclin T/chemistry/metabolism ; Cyclin-Dependent Kinase 9/metabolism ; Cyclin-Dependent Kinases/metabolism ; HeLa Cells ; Humans ; Hydrophobic and Hydrophilic Interactions ; Phosphorylation ; Positive Transcriptional Elongation Factor B/metabolism ; Protein Domains ; Protein-Serine-Threonine Kinases/metabolism ; Protein-Tyrosine Kinases/metabolism ; RNA Polymerase II/*chemistry/*metabolism ; Transcription Elongation, Genetic ; Transcription Factor TFIIH/metabolism ; Transcriptional Activation ; }, abstract = {Hyperphosphorylation of the C-terminal domain (CTD) of the RPB1 subunit of human RNA polymerase (Pol) II is essential for transcriptional elongation and mRNA processing1-3. The CTD contains 52 heptapeptide repeats of the consensus sequence YSPTSPS. The highly repetitive nature and abundant possible phosphorylation sites of the CTD exert special constraints on the kinases that catalyse its hyperphosphorylation. Positive transcription elongation factor b (P-TEFb)-which consists of CDK9 and cyclin T1-is known to hyperphosphorylate the CTD and negative elongation factors to stimulate Pol II elongation1,4,5. The sequence determinant on P-TEFb that facilitates this action is currently unknown. Here we identify a histidine-rich domain in cyclin T1 that promotes the hyperphosphorylation of the CTD and stimulation of transcription by CDK9. The histidine-rich domain markedly enhances the binding of P-TEFb to the CTD and functional engagement with target genes in cells. In addition to cyclin T1, at least one other kinase-DYRK1A 6 -also uses a histidine-rich domain to target and hyperphosphorylate the CTD. As a low-complexity domain, the histidine-rich domain also promotes the formation of phase-separated liquid droplets in vitro, and the localization of P-TEFb to nuclear speckles that display dynamic liquid properties and are sensitive to the disruption of weak hydrophobic interactions. The CTD-which in isolation does not phase separate, despite being a low-complexity domain-is trapped within the cyclin T1 droplets, and this process is enhanced upon pre-phosphorylation by CDK7 of transcription initiation factor TFIIH1-3. By using multivalent interactions to create a phase-separated functional compartment, the histidine-rich domain in kinases targets the CTD into this environment to ensure hyperphosphorylation and efficient elongation of Pol II.}, } @article {pmid29849145, year = {2018}, author = {Domingo, J and Diss, G and Lehner, B}, title = {Pairwise and higher-order genetic interactions during the evolution of a tRNA.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {117-121}, pmid = {29849145}, issn = {1476-4687}, support = {616434//European Research Council/International ; }, mesh = {Epistasis, Genetic ; *Evolution, Molecular ; Genetic Fitness ; Genotype ; *Mutation ; Phylogeny ; RNA, Transfer/*genetics ; Saccharomyces cerevisiae/*genetics ; Sequence Alignment ; }, abstract = {A central question in genetics and evolution is the extent to which the outcomes of mutations change depending on the genetic context in which they occur1-3. Pairwise interactions between mutations have been systematically mapped within4-18 and between 19 genes, and have been shown to contribute substantially to phenotypic variation among individuals 20 . However, the extent to which genetic interactions themselves are stable or dynamic across genotypes is unclear21, 22. Here we quantify more than 45,000 genetic interactions between the same 87 pairs of mutations across more than 500 closely related genotypes of a yeast tRNA. Notably, all pairs of mutations interacted in at least 9% of genetic backgrounds and all pairs switched from interacting positively to interacting negatively in different genotypes (false discovery rate < 0.1). Higher-order interactions are also abundant and dynamic across genotypes. The epistasis in this tRNA means that all individual mutations switch from detrimental to beneficial, even in closely related genotypes. As a consequence, accurate genetic prediction requires mutation effects to be measured across different genetic backgrounds and the use of higher-order epistatic terms.}, } @article {pmid29849144, year = {2018}, author = {Van Zee, NJ and Adelizzi, B and Mabesoone, MFJ and Meng, X and Aloi, A and Zha, RH and Lutz, M and Filot, IAW and Palmans, ARA and Meijer, EW}, title = {Potential enthalpic energy of water in oils exploited to control supramolecular structure.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {100-103}, doi = {10.1038/s41586-018-0169-0}, pmid = {29849144}, issn = {1476-4687}, abstract = {Water directs the self-assembly of both natural1,2 and synthetic3-9 molecules to form precise yet dynamic structures. Nevertheless, our molecular understanding of the role of water in such systems is incomplete, which represents a fundamental constraint in the development of supramolecular materials for use in biomaterials, nanoelectronics and catalysis 10 . In particular, despite the widespread use of alkanes as solvents in supramolecular chemistry11,12, the role of water in the formation of aggregates in oils is not clear, probably because water is only sparingly miscible in these solvents-typical alkanes contain less than 0.01 per cent water by weight at room temperature 13 . A notable and unused feature of this water is that it is essentially monomeric 14 . It has been determined previously 15 that the free energy cost of forming a cavity in alkanes that is large enough for a water molecule is only just compensated by its interaction with the interior of the cavity; this cost is therefore too high to accommodate clusters of water. As such, water molecules in alkanes possess potential enthalpic energy in the form of unrealized hydrogen bonds. Here we report that this energy is a thermodynamic driving force for water molecules to interact with co-dissolved hydrogen-bond-based aggregates in oils. By using a combination of spectroscopic, calorimetric, light-scattering and theoretical techniques, we demonstrate that this interaction can be exploited to modulate the structure of one-dimensional supramolecular polymers.}, } @article {pmid29849143, year = {2018}, author = {Lowery, CM and Bralower, TJ and Owens, JD and Rodríguez-Tovar, FJ and Jones, H and Smit, J and Whalen, MT and Claeys, P and Farley, K and Gulick, SPS and Morgan, JV and Green, S and Chenot, E and Christeson, GL and Cockell, CS and Coolen, MJL and Ferrière, L and Gebhardt, C and Goto, K and Kring, DA and Lofi, J and Ocampo-Torres, R and Perez-Cruz, L and Pickersgill, AE and Poelchau, MH and Rae, ASP and Rasmussen, C and Rebolledo-Vieyra, M and Riller, U and Sato, H and Tikoo, SM and Tomioka, N and Urrutia-Fucugauchi, J and Vellekoop, J and Wittmann, A and Xiao, L and Yamaguchi, KE and Zylberman, W}, title = {Rapid recovery of life at ground zero of the end-Cretaceous mass extinction.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {288-291}, pmid = {29849143}, issn = {1476-4687}, support = {NNX16AJ60G/NASA/NASA/United States ; }, mesh = {*Biodiversity ; Calcium/metabolism ; *Extinction, Biological ; Foraminifera/isolation & purification ; Fossils ; Gulf of Mexico ; History, Ancient ; *Life ; Magnesium/metabolism ; Oxygen/metabolism ; Plankton/isolation & purification ; Sample Size ; Species Specificity ; Time Factors ; }, abstract = {The Cretaceous/Palaeogene mass extinction eradicated 76% of species on Earth1,2. It was caused by the impact of an asteroid3,4 on the Yucatán carbonate platform in the southern Gulf of Mexico 66 million years ago 5 , forming the Chicxulub impact crater6,7. After the mass extinction, the recovery of the global marine ecosystem-measured as primary productivity-was geographically heterogeneous 8 ; export production in the Gulf of Mexico and North Atlantic-western Tethys was slower than in most other regions8-11, taking 300 thousand years (kyr) to return to levels similar to those of the Late Cretaceous period. Delayed recovery of marine productivity closer to the crater implies an impact-related environmental control, such as toxic metal poisoning 12 , on recovery times. If no such geographic pattern exists, the best explanation for the observed heterogeneity is a combination of ecological factors-trophic interactions 13 , species incumbency and competitive exclusion by opportunists 14 -and 'chance'8,15,16. The question of whether the post-impact recovery of marine productivity was delayed closer to the crater has a bearing on the predictability of future patterns of recovery in anthropogenically perturbed ecosystems. If there is a relationship between the distance from the impact and the recovery of marine productivity, we would expect recovery rates to be slowest in the crater itself. Here we present a record of foraminifera, calcareous nannoplankton, trace fossils and elemental abundance data from within the Chicxulub crater, dated to approximately the first 200 kyr of the Palaeocene. We show that life reappeared in the basin just years after the impact and a high-productivity ecosystem was established within 30 kyr, which indicates that proximity to the impact did not delay recovery and that there was therefore no impact-related environmental control on recovery. Ecological processes probably controlled the recovery of productivity after the Cretaceous/Palaeogene mass extinction and are therefore likely to be important for the response of the ocean ecosystem to other rapid extinction events.}, } @article {pmid29849142, year = {2018}, author = {Goedert, J and Lécuyer, C and Amiot, R and Arnaud-Godet, F and Wang, X and Cui, L and Cuny, G and Douay, G and Fourel, F and Panczer, G and Simon, L and Steyer, JS and Zhu, M}, title = {Euryhaline ecology of early tetrapods revealed by stable isotopes.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {68-72}, doi = {10.1038/s41586-018-0159-2}, pmid = {29849142}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/classification ; *Biological Evolution ; Bone and Bones/chemistry ; *Ecosystem ; Fishes/classification ; Fresh Water/chemistry ; Isotopes/analysis ; Paleontology ; Phylogeny ; Seawater/chemistry ; Vertebrates/*classification ; }, abstract = {The fish-to-tetrapod transition-followed later by terrestrialization-represented a major step in vertebrate evolution that gave rise to a successful clade that today contains more than 30,000 tetrapod species. The early tetrapod Ichthyostega was discovered in 1929 in the Devonian Old Red Sandstone sediments of East Greenland (dated to approximately 365 million years ago). Since then, our understanding of the fish-to-tetrapod transition has increased considerably, owing to the discovery of additional Devonian taxa that represent early tetrapods or groups evolutionarily close to them. However, the aquatic environment of early tetrapods and the vertebrate fauna associated with them has remained elusive and highly debated. Here we use a multi-stable isotope approach (δ13C, δ18O and δ34S) to show that some Devonian vertebrates, including early tetrapods, were euryhaline and inhabited transitional aquatic environments subject to high-magnitude, rapid changes in salinity, such as estuaries or deltas. Euryhalinity may have predisposed the early tetrapod clade to be able to survive Late Devonian biotic crises and then successfully colonize terrestrial environments.}, } @article {pmid29849141, year = {2018}, author = {Fraietta, JA and Nobles, CL and Sammons, MA and Lundh, S and Carty, SA and Reich, TJ and Cogdill, AP and Morrissette, JJD and DeNizio, JE and Reddy, S and Hwang, Y and Gohil, M and Kulikovskaya, I and Nazimuddin, F and Gupta, M and Chen, F and Everett, JK and Alexander, KA and Lin-Shiao, E and Gee, MH and Liu, X and Young, RM and Ambrose, D and Wang, Y and Xu, J and Jordan, MS and Marcucci, KT and Levine, BL and Garcia, KC and Zhao, Y and Kalos, M and Porter, DL and Kohli, RM and Lacey, SF and Berger, SL and Bushman, FD and June, CH and Melenhorst, JJ}, title = {Disruption of TET2 promotes the therapeutic efficacy of CD19-targeted T cells.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {307-312}, doi = {10.1038/s41586-018-0178-z}, pmid = {29849141}, issn = {1476-4687}, support = {P01 CA214278/CA/NCI NIH HHS/United States ; R01 AI082020/AI/NIAID NIH HHS/United States ; R01 AI104400/AI/NIAID NIH HHS/United States ; U19 AI117950/AI/NIAID NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; P30 AI045008/AI/NIAID NIH HHS/United States ; U01 AI104400/AI/NIAID NIH HHS/United States ; R01 GM118501/GM/NIGMS NIH HHS/United States ; K08 AI101008/AI/NIAID NIH HHS/United States ; R01 CA078831/CA/NCI NIH HHS/United States ; R01 CA165206/CA/NCI NIH HHS/United States ; }, mesh = {5-Methylcytosine/*metabolism ; Adoptive Transfer ; Aged ; Alleles ; Antigens, CD19/*immunology ; Cell Differentiation ; Clinical Trials as Topic ; Clone Cells/cytology/immunology ; Dioxygenases/*genetics/metabolism ; Epigenesis, Genetic ; HEK293 Cells ; Humans ; Immunotherapy/*methods ; Leukemia, Lymphocytic, Chronic, B-Cell/genetics/*immunology/pathology/*therapy ; Male ; Mutation ; Recombinant Fusion Proteins/genetics/metabolism ; T-Lymphocytes/cytology/*immunology/metabolism/*transplantation ; Transgenes ; }, abstract = {Cancer immunotherapy based on genetically redirecting T cells has been used successfully to treat B cell malignancies1-3. In this strategy, the T cell genome is modified by integration of viral vectors or transposons encoding chimaeric antigen receptors (CARs) that direct tumour cell killing. However, this approach is often limited by the extent of expansion and persistence of CAR T cells4,5. Here we report mechanistic insights from studies of a patient with chronic lymphocytic leukaemia treated with CAR T cells targeting the CD19 protein. Following infusion of CAR T cells, anti-tumour activity was evident in the peripheral blood, lymph nodes and bone marrow; this activity was accompanied by complete remission. Unexpectedly, at the peak of the response, 94% of CAR T cells originated from a single clone in which lentiviral vector-mediated insertion of the CAR transgene disrupted the methylcytosine dioxygenase TET2 gene. Further analysis revealed a hypomorphic mutation in this patient's second TET2 allele. TET2-disrupted CAR T cells exhibited an epigenetic profile consistent with altered T cell differentiation and, at the peak of expansion, displayed a central memory phenotype. Experimental knockdown of TET2 recapitulated the potency-enhancing effect of TET2 dysfunction in this patient's CAR T cells. These findings suggest that the progeny of a single CAR T cell induced leukaemia remission and that TET2 modification may be useful for improving immunotherapies.}, } @article {pmid29849140, year = {2018}, author = {Chan, LN and Chen, Z and Braas, D and Lee, JW and Xiao, G and Geng, H and Cosgun, KN and Hurtz, C and Shojaee, S and Cazzaniga, V and Schjerven, H and Ernst, T and Hochhaus, A and Kornblau, SM and Konopleva, M and Pufall, MA and Cazzaniga, G and Liu, GJ and Milne, TA and Koeffler, HP and Ross, TS and Sánchez-García, I and Borkhardt, A and Yamamoto, KR and Dickins, RA and Graeber, TG and Müschen, M}, title = {Author Correction: Metabolic gatekeeper function of B-lymphoid transcription factors.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {E5}, doi = {10.1038/s41586-018-0164-5}, pmid = {29849140}, issn = {1476-4687}, abstract = {In Fig. 3c of this Letter, the the effects of CRISPR-Cas9-mediated deletion of NR3C1, TXNIP and CNR2 in patient-derived B-lineage leukaemia cells were shown. For curves depicting NR3C1 (left graph), data s for TXNIP (middle graph) were inadvertently plotted. This figure has been corrected online, and the original Fig. 3c is shown as Supplementary Information to this Amendment for transparency. The error does not affect the conclusions of the Letter. In addition, Source Data files have been added for the Figs. 1-4 and Extended Data Figs. 1-10 of the original Letter.}, } @article {pmid29849139, year = {2018}, author = {Beyaz, S and Mana, MD and Roper, J and Kedrin, D and Saadatpour, A and Hong, SJ and Bauer-Rowe, KE and Xifaras, ME and Akkad, A and Arias, E and Pinello, L and Katz, Y and Shinagare, S and Abu-Remaileh, M and Mihaylova, MM and Lamming, DW and Dogum, R and Guo, G and Bell, GW and Selig, M and Nielsen, GP and Gupta, N and Ferrone, CR and Deshpande, V and Yuan, GC and Orkin, SH and Sabatini, DM and Yilmaz, ÖH}, title = {Author Correction: High-fat diet enhances stemness and tumorigenicity of intestinal progenitors.}, journal = {Nature}, volume = {560}, number = {7717}, pages = {E26}, doi = {10.1038/s41586-018-0187-y}, pmid = {29849139}, issn = {1476-4687}, abstract = {In Fig. 4e of this Article, the labels for 'Control' and 'HFD' were reversed ('Control' should have been labelled blue rather than purple, and 'HFD' should have been labelled purple rather than blue). Similarly, in Fig. 4f of this Article, the labels for 'V' and 'GW' were reversed ('V' should have been labelled blue rather than purple, and 'GW' should have been labelled purple instead of blue). The original figure has been corrected online.}, } @article {pmid29849062, year = {2018}, author = {Kyrmizi, I and Ferreira, H and Carvalho, A and Figueroa, JAL and Zarmpas, P and Cunha, C and Akoumianaki, T and Stylianou, K and Deepe, GS and Samonis, G and Lacerda, JF and Campos, A and Kontoyiannis, DP and Mihalopoulos, N and Kwon-Chung, KJ and El-Benna, J and Valsecchi, I and Beauvais, A and Brakhage, AA and Neves, NM and Latge, JP and Chamilos, G}, title = {Calcium sequestration by fungal melanin inhibits calcium-calmodulin signalling to prevent LC3-associated phagocytosis.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {791-803}, doi = {10.1038/s41564-018-0167-x}, pmid = {29849062}, issn = {2058-5276}, abstract = {LC3-associated phagocytosis (LAP) is a non-canonical autophagy pathway regulated by Rubicon, with an emerging role in immune homeostasis and antifungal host defence. Aspergillus cell wall melanin protects conidia (spores) from killing by phagocytes and promotes pathogenicity through blocking nicotinamide adenine dinucleotide phosphate (NADPH) oxidase-dependent activation of LAP. However, the signalling regulating LAP upstream of Rubicon and the mechanism of melanin-induced inhibition of this pathway remain incompletely understood. Herein, we identify a Ca2+ signalling pathway that depends on intracellular Ca2+ sources from endoplasmic reticulum, endoplasmic reticulum-phagosome communication, Ca2+ release from phagosome lumen and calmodulin (CaM) recruitment, as a master regulator of Rubicon, the phagocyte NADPH oxidase NOX2 and other molecular components of LAP. Furthermore, we provide genetic evidence for the physiological importance of Ca2+-CaM signalling in aspergillosis. Finally, we demonstrate that Ca2+ sequestration by Aspergillus melanin inside the phagosome abrogates activation of Ca2+-CaM signalling to inhibit LAP. These findings reveal the important role of Ca2+-CaM signalling in antifungal immunity and identify an immunological function of Ca2+ binding by melanin pigments with broad physiological implications beyond fungal disease pathogenesis.}, } @article {pmid29848637, year = {2018}, author = {Mann, A}, title = {News Feature: Life after the asteroid apocalypse.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5820-5823}, doi = {10.1073/pnas.1807339115}, pmid = {29848637}, issn = {1091-6490}, } @article {pmid29848636, year = {2018}, author = {Ge, C and Zhu, C and Francisco, JS and Zeng, XC and Wang, J}, title = {A molecular perspective for global modeling of upper atmospheric NH3 from freezing clouds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6147-6152}, pmid = {29848636}, issn = {1091-6490}, abstract = {Ammonia plays a key role in the neutralization of atmospheric acids such as sulfate and nitrates. A few in situ observations have supported the theory that gas-phase NH3 concentrations should decrease sharply with altitude and be extremely low in the upper troposphere and lower stratosphere (UTLS). This theory, however, seems inconsistent with recent satellite measurements and is also not supported by the aircraft data showing highly or fully neutralized sulfate aerosol particles by ammonium in the UTLS in many parts of the world. Here we reveal the contributions of deep convective clouds to NH3 in the UTLS by using integrated cross-scale modeling, which includes molecular dynamic simulations, a global chemistry transport model, and satellite and aircraft measurements. We show that the NH3 dissolved in liquid cloud droplets is prone to being released into the UTLS upon freezing during deep convection. Because NH3 emission is not regulated in most countries and its future increase is likely persistent from agricultural growth and the warmer climate, the effect of NH3 on composition and phase of aerosol particles in the UTLS can be significant, which in turn can affect cirrus cloud formation, radiation, and the budgets of NOx and O3.}, } @article {pmid29848635, year = {2018}, author = {Alfaro, ME}, title = {Resolving the ray-finned fish tree of life.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6107-6109}, doi = {10.1073/pnas.1807018115}, pmid = {29848635}, issn = {1091-6490}, mesh = {Animals ; *Fishes ; Life ; *Phylogeny ; }, } @article {pmid29848634, year = {2018}, author = {Wang, M and Roux, F and Bartoli, C and Huard-Chauveau, C and Meyer, C and Lee, H and Roby, D and McPeek, MS and Bergelson, J}, title = {Two-way mixed-effects methods for joint association analysis using both host and pathogen genomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5440-E5449}, pmid = {29848634}, issn = {1091-6490}, support = {R01 GM083068/GM/NIGMS NIH HHS/United States ; R01 HG001645/HG/NHGRI NIH HHS/United States ; }, mesh = {Arabidopsis/*genetics ; Chromosome Mapping/methods ; Disease Resistance/genetics ; Genetic Variation/genetics ; Genome/*genetics ; Genome-Wide Association Study/methods ; Host-Pathogen Interactions/*genetics ; Phenotype ; Quantitative Trait Loci/genetics ; Xanthomonas/genetics ; }, abstract = {Infectious diseases are often affected by specific pairings of hosts and pathogens and therefore by both of their genomes. The integration of a pair of genomes into genome-wide association mapping can provide an exquisitely detailed view of the genetic landscape of complex traits. We present a statistical method, ATOMM (Analysis with a Two-Organism Mixed Model), that maps a trait of interest to a pair of genomes simultaneously; this method makes use of whole-genome sequence data for both host and pathogen organisms. ATOMM uses a two-way mixed-effect model to test for genetic associations and cross-species genetic interactions while accounting for sample structure including interactions between the genetic backgrounds of the two organisms. We demonstrate the applicability of ATOMM to a joint association study of quantitative disease resistance (QDR) in the Arabidopsis thaliana-Xanthomonas arboricola pathosystem. Our method uncovers a clear host-strain specificity in QDR and provides a powerful approach to identify genetic variants on both genomes that contribute to phenotypic variation.}, } @article {pmid29848633, year = {2018}, author = {Liu, JL and Zhang, WQ and Huang, MY}, title = {Transcriptional signature of the decidua in preeclampsia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5434-E5436}, pmid = {29848633}, issn = {1091-6490}, mesh = {*Decidua ; Female ; Humans ; Placenta ; *Pre-Eclampsia ; Pregnancy ; }, } @article {pmid29848632, year = {2018}, author = {Spyropoulos, G and Bosman, CA and Fries, P}, title = {A theta rhythm in macaque visual cortex and its attentional modulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5614-E5623}, pmid = {29848632}, issn = {1091-6490}, support = {U54 MH091657/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Attention/*physiology ; Electrocorticography/methods ; Evoked Potentials, Visual/physiology ; Macaca ; Male ; Neurons/physiology ; Photic Stimulation/methods ; Theta Rhythm/*physiology ; Visual Cortex/*physiology ; Visual Fields/physiology ; Visual Perception/physiology ; }, abstract = {Theta rhythms govern rodent sniffing and whisking, and human language processing. Human psychophysics suggests a role for theta also in visual attention. However, little is known about theta in visual areas and its attentional modulation. We used electrocorticography (ECoG) to record local field potentials (LFPs) simultaneously from areas V1, V2, V4, and TEO of two macaque monkeys performing a selective visual attention task. We found a ≈4-Hz theta rhythm within both the V1-V2 and the V4-TEO region, and theta synchronization between them, with a predominantly feedforward directed influence. ECoG coverage of large parts of these regions revealed a surprising spatial correspondence between theta and visually induced gamma. Furthermore, gamma power was modulated with theta phase. Selective attention to the respective visual stimulus strongly reduced these theta-rhythmic processes, leading to an unusually strong attention effect for V1. Microsaccades (MSs) were partly locked to theta. However, neuronal theta rhythms tended to be even more pronounced for epochs devoid of MSs. Thus, we find an MS-independent theta rhythm specific to visually driven parts of V1-V2, which rhythmically modulates local gamma and entrains V4-TEO, and which is strongly reduced by attention. We propose that the less theta-rhythmic and thereby more continuous processing of the attended stimulus serves the exploitation of this behaviorally most relevant information. The theta-rhythmic and thereby intermittent processing of the unattended stimulus likely reflects the ecologically important exploration of less relevant sources of information.}, } @article {pmid29848631, year = {2018}, author = {Seguin, C and van den Heuvel, MP and Zalesky, A}, title = {Navigation of brain networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6297-6302}, doi = {10.1073/pnas.1801351115}, pmid = {29848631}, issn = {1091-6490}, support = {U54 MH091657/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Animals ; Brain/*physiology ; Computer Simulation ; Connectome/methods ; Female ; Humans ; Macaca ; Male ; Mice ; Models, Neurological ; Nerve Net/physiology ; Neural Pathways/*physiology ; Young Adult ; }, abstract = {Understanding the mechanisms of neural communication in large-scale brain networks remains a major goal in neuroscience. We investigated whether navigation is a parsimonious routing model for connectomics. Navigating a network involves progressing to the next node that is closest in distance to a desired destination. We developed a measure to quantify navigation efficiency and found that connectomes in a range of mammalian species (human, mouse, and macaque) can be successfully navigated with near-optimal efficiency (>80% of optimal efficiency for typical connection densities). Rewiring network topology or repositioning network nodes resulted in 45-60% reductions in navigation performance. We found that the human connectome cannot be progressively randomized or clusterized to result in topologies with substantially improved navigation performance (>5%), suggesting a topological balance between regularity and randomness that is conducive to efficient navigation. Navigation was also found to (i) promote a resource-efficient distribution of the information traffic load, potentially relieving communication bottlenecks, and (ii) explain significant variation in functional connectivity. Unlike commonly studied communication strategies in connectomics, navigation does not mandate assumptions about global knowledge of network topology. We conclude that the topology and geometry of brain networks are conducive to efficient decentralized communication.}, } @article {pmid29848630, year = {2018}, author = {Jia, S and Wang, X and Yuan, Z and Lin, F and Ye, J and Hao, Z and Luskin, MS}, title = {Global signal of top-down control of terrestrial plant communities by herbivores.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6237-6242}, pmid = {29848630}, issn = {1091-6490}, mesh = {Animals ; Biodiversity ; Biomass ; Climate ; Ecosystem ; Herbivory/*physiology ; Plants ; }, abstract = {The theory of "top-down" ecological regulation predicts that herbivory suppresses plant abundance, biomass, and survival but increases diversity through the disproportionate consumption of dominant species, which inhibits competitive exclusion. To date, these outcomes have been clear in aquatic ecosystems but not on land. We explicate this discrepancy using a meta-analysis of experimental results from 123 native animal exclusions in natural terrestrial ecosystems (623 pairwise comparisons). Consistent with top-down predictions, we found that herbivores significantly reduced plant abundance, biomass, survival, and reproduction (all P < 0.01) and increased species evenness but not richness (P = 0.06 and P = 0.59, respectively). However, when examining patterns in the strength of top-down effects, with few exceptions, we were unable to detect significantly different effect sizes among biomes, based on local site characteristics (climate or productivity) or study characteristics (study duration or exclosure size). The positive effects on diversity were only significant in studies excluding large animals or located in temperate grasslands. The results demonstrate that top-down regulation by herbivores is a pervasive process shaping terrestrial plant communities at the global scale, but its strength is highly site specific and not predicted by basic site conditions. We suggest that including herbivore densities as a covariate in future exclosure studies will facilitate the discovery of unresolved macroecology trends in the strength of herbivore-plant interactions.}, } @article {pmid29848629, year = {2018}, author = {Lee, JH and Chandrasekar, S and Chung, S and Hwang Fu, YH and Liu, D and Weiss, S and Shan, SO}, title = {Sequential activation of human signal recognition particle by the ribosome and signal sequence drives efficient protein targeting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5487-E5496}, doi = {10.1073/pnas.1802252115}, pmid = {29848629}, issn = {1091-6490}, support = {R01 GM078024/GM/NIGMS NIH HHS/United States ; }, mesh = {Endoplasmic Reticulum/metabolism ; Escherichia coli/metabolism ; Humans ; Peptides/metabolism ; Protein Binding/physiology ; Protein Biosynthesis/physiology ; Protein Sorting Signals/*physiology ; Protein Transport/*physiology ; Receptors, Cytoplasmic and Nuclear/metabolism ; Receptors, Peptide/metabolism ; Ribosomes/*metabolism ; Signal Recognition Particle/*metabolism ; }, abstract = {Signal recognition particle (SRP) is a universally conserved targeting machine that mediates the targeted delivery of ∼30% of the proteome. The molecular mechanism by which eukaryotic SRP achieves efficient and selective protein targeting remains elusive. Here, we describe quantitative analyses of completely reconstituted human SRP (hSRP) and SRP receptor (SR). Enzymatic and fluorescence analyses showed that the ribosome, together with a functional signal sequence on the nascent polypeptide, are required to activate SRP for rapid recruitment of the SR, thereby delivering translating ribosomes to the endoplasmic reticulum. Single-molecule fluorescence spectroscopy combined with cross-complementation analyses reveal a sequential mechanism of activation whereby the ribosome unlocks the hSRP from an autoinhibited state and primes SRP to sample a variety of conformations. The signal sequence further preorganizes the mammalian SRP into the optimal conformation for efficient recruitment of the SR. Finally, the use of a signal sequence to activate SRP for receptor recruitment is a universally conserved feature to enable efficient and selective protein targeting, and the eukaryote-specific components confer upon the mammalian SRP the ability to sense and respond to ribosomes.}, } @article {pmid29848628, year = {2018}, author = {Borlongan, CV}, title = {Fatty acid chemical mediator provides insights into the pathology and treatment of Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6322-6324}, pmid = {29848628}, issn = {1091-6490}, mesh = {*Fatty Acids ; Humans ; Mitochondria ; *Parkinson Disease ; }, } @article {pmid29848627, year = {2018}, author = {Vagni, G and Cornwell, B}, title = {Patterns of everyday activities across social contexts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6183-6188}, pmid = {29848627}, issn = {1091-6490}, mesh = {Cluster Analysis ; Databases, Factual ; Human Activities/*statistics & numerical data ; Humans ; *Periodicity ; *Social Behavior ; Sociology ; Time Factors ; }, abstract = {Social-scientific theory and research give rise to conflicting expectations regarding the extent to which individuals' everyday lives in modern society follow predictable patterns of behavior. Much previous research has addressed this issue implicitly by documenting widespread trends in patterns of "time use" or "time allocation," including trends in time devoted to paid work, unpaid work, and leisure. This study expands on this research by examining common patterns with respect to not how much time individuals spend on certain everyday activities (e.g., leisure), but rather how those activities are sequenced throughout the day. Using sequence methods and cluster analysis, we analyze a large collection of harmonized time diaries from the Multinational Time Use Study (MTUS), including diaries from 23 countries and dating back to 1961. Our analysis of these diaries reveals eight common everyday sequence patterns-including different paid work, unpaid work, and leisure clusters. This same set of patterns reappears in a generally similar distribution across the different countries and time periods that are included in the MTUS sequence data. This study has implications for how analysts study time diary data and raises important questions about the causes and consequences of individuals' experiences with particular behavioral sequences.}, } @article {pmid29848380, year = {2018}, author = {Birhanu, TM and Birarra, MK and Mekonnen, FA}, title = {Compliance to iron and folic acid supplementation in pregnancy, Northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {345}, pmid = {29848380}, issn = {1756-0500}, mesh = {Adult ; Anemia/*prevention & control ; Cross-Sectional Studies ; Drug Prescriptions/standards/*statistics & numerical data ; Ethiopia ; Female ; Folic Acid/administration & dosage/*therapeutic use ; Humans ; Iron/administration & dosage/*therapeutic use ; Medication Adherence/*statistics & numerical data ; Pregnancy ; Pregnancy Complications, Hematologic/*prevention & control ; Prenatal Care/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: Strict compliance to iron and folic acid supplementation is vital for prevention of anemia in pregnancy. However, data are scarce in Ethiopia. So, we conducted this study to assess the level of compliance to iron and folic acid supplementation during pregnancy and its associated factors.

RESULTS: Of 418 women, over half, 231 (55.3%), adhered to the recommended iron and folic acid supplementation. Women who started antenatal care (ANC) follow up early [AOR; 95% CI 2.43 (1.12-5.26)], had more frequent number of ANC visit [AOR; 95% CI 2.73 (1.32-5.61)], took small number of tablets per visit [AOR; 95% CI 3.0 (1.21-7.43)], had history of anemia [AOR; 95% CI 1.9 (1.17-3.12)], and were from urban areas [AOR; 95% CI 2.2 (1.29-3.77)], were more likely to conform to recommended iron and folic acid supplementation. Therefore, there need to be prescription of the lowest possible number of tablets per visit. Furthermore, education targeting on increasing maternal health service utilization need to be in place. There need to also be further research aimed at determining the number of tablets to be prescribed per visit specific to individuals' background characteristics.}, } @article {pmid29848377, year = {2018}, author = {de Almeida, CC and Pizauro, LJL and Soltes, GA and Slavic, D and de Ávila, FA and Pizauro, JM and MacInnes, JI}, title = {Some coagulase negative Staphylococcus spp. isolated from buffalo can be misidentified as Staphylococcus aureus by phenotypic and Sa442 PCR methods.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {346}, pmid = {29848377}, issn = {1756-0500}, support = {070404//070404/ ; }, mesh = {Animals ; Brazil ; Buffaloes ; Coagulase/metabolism ; Female ; Mastitis/*microbiology ; Milk ; Real-Time Polymerase Chain Reaction/*standards ; Sequence Analysis, RNA/*standards ; Species Specificity ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*standards ; Staphylococcus/*isolation & purification ; Staphylococcus aureus/*isolation & purification ; }, abstract = {OBJECTIVE: Staphylococcus aureus is a commonly reported cause of buffalo mastitis. However, its prevalence may be overestimated. The aim of this study was to compare S. aureus identification by conventional phenotypic and genotypic assays versus Matrix-Assisted Laser Desorption Ionization-Time of Flight Mass Spectrometry (MALDI-TOF MS) and novel real-time quantitative PCR tests for the cytochrome oxidase subunit D II (cydB) and staphylocoagulase (coa) genes.

RESULTS: From 408 samples obtained from buffalo milk/milking environment, 32 putative S. aureus strains were identified based on characteristic growth on Baird Parker agar, positive catalase reaction, ability to clot rabbit plasma, and positive Sa442 PCR assay. However, in further testing, only 10 of these strains were positive in latex agglutination tests and by MALDI-TOF MS, only eight of the 32 strains were S. aureus while the rest were S. chromogenes (19), S. agnetis (3), S. cohnii (1), or S. xylosus (1). All eight strains identified as S. aureus by MALDI-TOF analysis and confirmed by 16S RNA gene sequencing were positive in a S. aureus-specific cydB PCR test. As well, 7/8 S. aureus strains were PCR positive in a real-time coa PCR test as were 2/69 S. chromogenes and the lone S. xylosus strain tested.}, } @article {pmid29848358, year = {2018}, author = {Olmos, JL and Pandey, S and Martin-Garcia, JM and Calvey, G and Katz, A and Knoska, J and Kupitz, C and Hunter, MS and Liang, M and Oberthuer, D and Yefanov, O and Wiedorn, M and Heyman, M and Holl, M and Pande, K and Barty, A and Miller, MD and Stern, S and Roy-Chowdhury, S and Coe, J and Nagaratnam, N and Zook, J and Verburgt, J and Norwood, T and Poudyal, I and Xu, D and Koglin, J and Seaberg, MH and Zhao, Y and Bajt, S and Grant, T and Mariani, V and Nelson, G and Subramanian, G and Bae, E and Fromme, R and Fung, R and Schwander, P and Frank, M and White, TA and Weierstall, U and Zatsepin, N and Spence, J and Fromme, P and Chapman, HN and Pollack, L and Tremblay, L and Ourmazd, A and Phillips, GN and Schmidt, M}, title = {Enzyme intermediates captured "on the fly" by mix-and-inject serial crystallography.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {59}, pmid = {29848358}, issn = {1741-7007}, support = {R01 GM117342/GM/NIGMS NIH HHS/United States ; R01 GM095583/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Ever since the first atomic structure of an enzyme was solved, the discovery of the mechanism and dynamics of reactions catalyzed by biomolecules has been the key goal for the understanding of the molecular processes that drive life on earth. Despite a large number of successful methods for trapping reaction intermediates, the direct observation of an ongoing reaction has been possible only in rare and exceptional cases.

RESULTS: Here, we demonstrate a general method for capturing enzyme catalysis "in action" by mix-and-inject serial crystallography (MISC). Specifically, we follow the catalytic reaction of the Mycobacterium tuberculosis β-lactamase with the third-generation antibiotic ceftriaxone by time-resolved serial femtosecond crystallography. The results reveal, in near atomic detail, antibiotic cleavage and inactivation from 30 ms to 2 s.

CONCLUSIONS: MISC is a versatile and generally applicable method to investigate reactions of biological macromolecules, some of which are of immense biological significance and might be, in addition, important targets for structure-based drug design. With megahertz X-ray pulse rates expected at the Linac Coherent Light Source II and the European X-ray free-electron laser, multiple, finely spaced time delays can be collected rapidly, allowing a comprehensive description of biomolecular reactions in terms of structure and kinetics from the same set of X-ray data.}, } @article {pmid29848336, year = {2018}, author = {Vazquez-Hernandez, C and Loza, A and Peguero-Sanchez, E and Segovia, L and Gutierrez-Rios, RM}, title = {Identification of reaction organization patterns that naturally cluster enzymatic transformations.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {63}, pmid = {29848336}, issn = {1752-0509}, support = {IN204515//PAPIIT-UNAM/ ; }, abstract = {BACKGROUND: Metabolic reactions are chemical transformations commonly catalyzed by enzymes. In recent years, the explosion of genomic data and individual experimental characterizations have contributed to the construction of databases and methodologies for the analysis of metabolic networks. Some methodologies based on graph theory organize compound networks into metabolic functional categories without preserving biochemical pathways. Other methods based on chemical group exchange and atom flow trace the conversion of substrates into products in detail, which is useful for inferring metabolic pathways.

METHODS: Here, we present a novel rule-based approach incorporating both methods that decomposes each reaction into architectures of compound pairs and loner compounds that can be organized into tree structures. We compared the tree structure-compound pairs to those reported in the KEGG-RPAIR dataset and obtained a match precision of 81%. The generated tree structures naturally clustered all reactions into general reaction patterns of compounds with similar chemical transformations. The match precision of each cluster was calculated and used to suggest reactant-pairs for which manual curation can be avoided because this is the main goal of the method. We evaluated catalytic processes in the clusters based on Enzyme Commission categories that revealed preferential use of enzyme classes.

CONCLUSIONS: We demonstrate that the application of simple rules can enable the identification of reaction patterns reflecting metabolic reactions that transform substrates into products and the types of catalysis involved in these transformations. Our rule-based approach can be incorporated as the input in pathfinders or as a tool for the construction of reaction classifiers, indicating its usefulness for predicting enzyme catalysis.}, } @article {pmid29848334, year = {2018}, author = {Orville, AM}, title = {Entering an era of dynamic structural biology….}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {55}, pmid = {29848334}, issn = {1741-7007}, support = {//Wellcome Trust/United Kingdom ; 102593//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Crystallography ; }, abstract = {A recent paper in BMC Biology presents a general method for mix-and-inject serial crystallography, to facilitate the visualization of enzyme intermediates via time-resolved serial femtosecond crystallography (tr-SFX). They apply their method to resolve in near atomic detail the cleavage and inactivation of the antibiotic ceftriaxone by a β-lactamase enzyme from Mycobacterium tuberculosis. Their work demonstrates the general applicability of time-resolved crystallography, from which dynamic structures, at atomic resolution, can be obtained.See research article: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0524-5 .}, } @article {pmid29848319, year = {2018}, author = {Bronstein, O and Kroh, A and Haring, E}, title = {Mind the gap! The mitochondrial control region and its power as a phylogenetic marker in echinoids.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {80}, pmid = {29848319}, issn = {1471-2148}, support = {P 29508//Austrian Science Fund FWF/Austria ; P 29508-B25//Austrian Science Fund/International ; }, mesh = {Algorithms ; Animals ; Base Sequence ; DNA Primers/metabolism ; DNA, Mitochondrial/genetics ; Genes, Mitochondrial ; Genetic Markers ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Mitochondria/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; RNA, Transfer/genetics ; Sea Urchins/*genetics ; }, abstract = {BACKGROUND: In Metazoa, mitochondrial markers are the most commonly used targets for inferring species-level molecular phylogenies due to their extremely low rate of recombination, maternal inheritance, ease of use and fast substitution rate in comparison to nuclear DNA. The mitochondrial control region (CR) is the main non-coding area of the mitochondrial genome and contains the mitochondrial origin of replication and transcription. While sequences of the cytochrome oxidase subunit 1 (COI) and 16S rRNA genes are the prime mitochondrial markers in phylogenetic studies, the highly variable CR is typically ignored and not targeted in such analyses. However, the higher substitution rate of the CR can be harnessed to infer the phylogeny of closely related species, and the use of a non-coding region alleviates biases resulting from both directional and purifying selection. Additionally, complete mitochondrial genome assemblies utilizing next generation sequencing (NGS) data often show exceptionally low coverage at specific regions, including the CR. This can only be resolved by targeted sequencing of this region.

RESULTS: Here we provide novel sequence data for the echinoid mitochondrial control region in over 40 species across the echinoid phylogenetic tree. We demonstrate the advantages of directly targeting the CR and adjacent tRNAs to facilitate complementing low coverage NGS data from complete mitochondrial genome assemblies. Finally, we test the performance of this region as a phylogenetic marker both in the lab and in phylogenetic analyses, and demonstrate its superior performance over the other available mitochondrial markers in echinoids.

CONCLUSIONS: Our target region of the mitochondrial CR (1) facilitates the first thorough investigation of this region across a wide range of echinoid taxa, (2) provides a tool for complementing missing data in NGS experiments, and (3) identifies the CR as a powerful, novel marker for phylogenetic inference in echinoids due to its high variability, lack of selection, and high compatibility across the entire class, outperforming conventional mitochondrial markers.}, } @article {pmid29848314, year = {2018}, author = {Preston, CC and Wyles, SP and Reyes, S and Storm, EC and Eckloff, BW and Faustino, RS}, title = {NUP155 insufficiency recalibrates a pluripotent transcriptome with network remodeling of a cardiogenic signaling module.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {62}, pmid = {29848314}, issn = {1752-0509}, support = {14SDG20380322//American Heart Association/ ; }, abstract = {BACKGROUND: Atrial fibrillation is a cardiac disease driven by numerous idiopathic etiologies. NUP155 is a nuclear pore complex protein that has been identified as a clinical driver of atrial fibrillation, yet the precise mechanism is unknown. The present study employs a systems biology algorithm to identify effects of NUP155 disruption on cardiogenicity in a model of stem cell-derived differentiation.

METHODS: Embryonic stem (ES) cell lines (n = 5) with truncated NUP155 were cultured in parallel with wild type (WT) ES cells (n = 5), and then harvested for RNAseq. Samples were run on an Illumina HiSeq 2000. Reads were analyzed using Strand NGS, Cytoscape, DAVID and Ingenuity Pathways Analysis to deconvolute the NUP155-disrupted transcriptome. Network topological analysis identified key features that controlled framework architecture and functional enrichment.

RESULTS: In NUP155 truncated ES cells, significant expression changes were detected in 326 genes compared to WT. These genes segregated into clusters that enriched for specific gene ontologies. Deconvolution of the collective framework into discrete sub-networks identified a module with the highest score that enriched for Cardiovascular System Development, and revealed NTRK1/TRKA and SRSF2/SC35 as critical hubs within this cardiogenic module.

CONCLUSIONS: The strategy of pluripotent transcriptome deconvolution used in the current study identified a novel association of NUP155 with potential drivers of arrhythmogenic AF. Here, NUP155 regulates cardioplasticity of a sub-network embedded within a larger framework of genome integrity, and exemplifies how transcriptome cardiogenicity in an embryonic stem cell genome is recalibrated by nucleoporin dysfunction.}, } @article {pmid29848313, year = {2018}, author = {Kocsisova, Z and Kornfeld, K and Schedl, T}, title = {Cell cycle accumulation of the proliferating cell nuclear antigen PCN-1 transitions from continuous in the adult germline to intermittent in the early embryo of C. elegans.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {12}, pmid = {29848313}, issn = {1471-213X}, support = {R01 AG02656106A1//National Institutes of Health (US)/International ; R01 GM100756/GM/NIGMS NIH HHS/United States ; DGE-1143954//National Science Foundation/International ; P40 OD010440/OD/NIH HHS/United States ; R01 GM100756/NH/NIH HHS/United States ; DGE-1745038//National Science Foundation/International ; R01 AG026561/AG/NIA NIH HHS/United States ; }, abstract = {BACKGROUND: The proliferating cell nuclear antigen (PCNA or PCN-1 in C. elegans), an essential processivity factor for DNA polymerase δ, has been widely used as a marker of S-phase. In C. elegans early embryos, PCN-1 accumulation is cyclic, localizing to the nucleus during S-phase and the cytoplasm during the rest of the cell cycle. The C. elegans larval and adult germline is an important model systems for studying cell cycle regulation, and it was observed that the cell cycle regulator cyclin E (CYE-1 in C. elegans) displays a non-cyclic, continuous accumulation pattern in this tissue. The accumulation pattern of PCN-1 has not been well defined in the larval and adult germline, and the objective of this study was to determine if the accumulation pattern is cyclic, as in other cells and organisms, or continuous, similar to cyclin E.

RESULTS: To study the larval and adult germline accumulation of PCN-1 expressed from its native locus, we used CRISPR/Cas9 technology to engineer a novel allele of pcn-1 that encodes an epitope-tagged protein. S-phase nuclei were labeled using EdU nucleotide incorporation, and FLAG::PCN-1 was detected by antibody staining. All progenitor zone nuclei, including those that were not in S-phase (as they were negative for EdU staining) showed PCN-1 accumulation, indicating that PCN-1 accumulated during all cell cycle phases in the germline progenitor zone. The same result was observed with a GFP::PCN-1 fusion protein expressed from a transgene. pcn-1 loss-of-function mutations were analyzed, and pcn-1 was necessary for robust fertility and embryonic development.

CONCLUSIONS: In the C. elegans early embryo as well as other organisms, PCN-1 accumulates in nuclei only during S-phase. By contrast, in the progenitor zone of the germline of C. elegans, PCN-1 accumulated in nuclei during all cell cycle stages. This pattern is similar to accumulation pattern of cyclin E. These observations support the model that mitotic cell cycle regulation in the germline stem and progenitor cells is distinct from somatic cells, as it does not heavily rely on cyclic accumulation of classic cell cycle proteins.}, } @article {pmid29848310, year = {2018}, author = {Kundu, S and Sharma, R}, title = {Origin, evolution, and divergence of plant class C GH9 endoglucanases.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {79}, pmid = {29848310}, issn = {1471-2148}, mesh = {Algorithms ; Amino Acid Motifs ; Amino Acid Sequence ; Bayes Theorem ; Calibration ; Cellulase/chemistry/classification/*genetics ; Cellulose ; *Evolution, Molecular ; Glycoside Hydrolases/genetics ; *Phylogeny ; Plants/*enzymology ; Protein Domains ; }, abstract = {BACKGROUND: Glycoside hydrolases of the GH9 family encode cellulases that predominantly function as endoglucanases and have wide applications in the food, paper, pharmaceutical, and biofuel industries. The partitioning of plant GH9 endoglucanases, into classes A, B, and C, is based on the differential presence of transmembrane, signal peptide, and the carbohydrate binding module (CBM49). There is considerable debate on the distribution and the functions of these enzymes which may vary in different organisms. In light of these findings we examined the origin, emergence, and subsequent divergence of plant GH9 endoglucanases, with an emphasis on elucidating the role of CBM49 in the digestion of crystalline cellulose by class C members.

RESULTS: Since, the digestion of crystalline cellulose mandates the presence of a well-defined set of aromatic and polar amino acids and/or an attributable domain that can mediate this conversion, we hypothesize a vertical mode of transfer of genes that could favour the emergence of class C like GH9 endoglucanase activity in land plants from potentially ancestral non plant taxa. We demonstrated the concomitant occurrence of a GH9 domain with CBM49 and other homologous carbohydrate binding modules, in putative endoglucanase sequences from several non-plant taxa. In the absence of comparable full length CBMs, we have characterized several low strength patterns that could approximate the CBM49, thereby, extending support for digestion of crystalline cellulose to other segments of the protein. We also provide data suggestive of the ancestral role of putative class C GH9 endoglucanases in land plants, which includes detailed phylogenetics and the presence and subsequent loss of CBM49, transmembrane, and signal peptide regions in certain populations of early land plants. These findings suggest that classes A and B of modern vascular land plants may have emerged by diverging directly from CBM49 encompassing putative class C enzymes.

CONCLUSION: Our detailed phylogenetic and bioinformatics analysis of putative GH9 endoglucanase sequences across major taxa suggests that plant class C enzymes, despite their recent discovery, could function as the last common ancestor of classes A and B. Additionally, research into their ability to digest or inter-convert crystalline and amorphous forms of cellulose could make them lucrative candidates for engineering biofuel feedstock.}, } @article {pmid29848309, year = {2018}, author = {Feng, K and Costa, J and Edwards, JS}, title = {Next-generation sequencing library construction on a surface.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {416}, pmid = {29848309}, issn = {1471-2164}, support = {R01 HG006876/HG/NHGRI NIH HHS/United States ; R01HG006876//National Human Genome Research Institute/ ; R43HG008582//National Human Genome Research Institute/ ; P30CA118100//National Cancer Institute/ ; }, mesh = {*Gene Library ; Genomics ; High-Throughput Nucleotide Sequencing/*methods ; Sequence Analysis, DNA/*methods ; Surface Properties ; Transposases/metabolism ; }, abstract = {BACKGROUND: Next-generation sequencing (NGS) has revolutionized almost all fields of biology, agriculture and medicine, and is widely utilized to analyse genetic variation. Over the past decade, the NGS pipeline has been steadily improved, and the entire process is currently relatively straightforward. However, NGS instrumentation still requires upfront library preparation, which can be a laborious process, requiring significant hands-on time. Herein, we present a simple but robust approach to streamline library preparation by utilizing surface bound transposases to construct DNA libraries directly on a flowcell surface.

RESULTS: The surface bound transposases directly fragment genomic DNA while simultaneously attaching the library molecules to the flowcell. We sequenced and analysed a Drosophila genome library generated by this surface tagmentation approach, and we showed that our surface bound library quality was comparable to the quality of the library from a commercial kit. In addition to the time and cost savings, our approach does not require PCR amplification of the library, which eliminates potential problems associated with PCR duplicates.

CONCLUSIONS: We described the first study to construct libraries directly on a flowcell. We believe our technique could be incorporated into the existing Illumina sequencing pipeline to simplify the workflow, reduce costs, and improve data quality.}, } @article {pmid29848308, year = {2018}, author = {Fornefett, J and Krause, J and Klose, K and Fingas, F and Hassert, R and Benga, L and Grunwald, T and Müller, U and Schrödl, W and Baums, CG}, title = {Comparative analysis of humoral immune responses and pathologies of BALB/c and C57BL/6 wildtype mice experimentally infected with a highly virulent Rodentibacter pneumotropicus (Pasteurella pneumotropica) strain.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {45}, pmid = {29848308}, issn = {1471-2180}, abstract = {BACKGROUND: Mice are a natural host for Rodentibacter (R.) pneumotropicus. Despite specific monitoring, it is still one of the most important infectious agents in laboratory animals. The objective of this study was to determine the virulence of a prevalent pathotype of R. pneumotropicus and characterize the host response in a new animal model.

RESULTS: Intranasal infection of C57BL/6 and BALB/c mice with a R. pneumotropicus strain (JF4Ni) bearing the genes of the three known repeats in toxin (RTX) toxins resulted in an unprecedented high mortality and morbidity above 50 and 80%, respectively. Morbidity was associated with severe weight loss as well as conjunctivitis and dyspnea. A main pathology was a catarrhal purulent to necrotic bronchopneumonia. Specific immune globuline (Ig) A was detected in tracheonasal lavages of most surviving mice which were still colonized by R. pneumotropicus. Furthermore, all surviving animals showed a distinct production of IgG antibodies. To differentiate T-helper cell (Th) 1 and Th2 immune responses we used subclasses of IgGs as indicators. Mean ratios of IgG2b to IgG1 were below 0.8 in sera drawn from both mice strains prior infection and from BALB/c mice post infection. In contrast, C57BL/6 mice had a mean IgG2b/IgG1 ratio of 1.6 post infection indicating a Th1 immune response in C57BL/6 versus a Th2 response in BALB/c mice associated with a tenfold higher bacterial load in the lung. In accordance with a Th1 response high antigen-specific IgG2c titers were detected in the majority of surviving C57BL/6 mice.

CONCLUSIONS: R. pneumotropicus JF4Ni is a highly virulent strain causing severe pneumonia and septicemia after intranasal infection of C57BL/6 and BALB/c mice. Persisting infections in the two mice strains are associated with Th1 and Th2 immune responses, respectively, and differences in the bacterial burden of the lung. The described model is ideally suited for future vaccination studies using the natural host.}, } @article {pmid29848307, year = {2018}, author = {Rasoolizadeh, A and Labbé, C and Sonah, H and Deshmukh, RK and Belzile, F and Menzies, JG and Bélanger, RR}, title = {Silicon protects soybean plants against Phytophthora sojae by interfering with effector-receptor expression.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {97}, pmid = {29848307}, issn = {1471-2229}, mesh = {*Disease Resistance ; Gene Expression Regulation, Plant ; Gene Ontology ; Host-Pathogen Interactions ; Phytophthora/*physiology ; Plant Diseases/*immunology/parasitology ; Plant Proteins/genetics/*metabolism ; Plant Roots/drug effects/genetics/immunology/physiology ; Signal Transduction ; Silicon/metabolism/*pharmacology ; Soybeans/drug effects/*genetics/immunology/physiology ; *Transcriptome ; Virulence ; }, abstract = {BACKGROUND: Silicon (Si) is known to protect against biotrophic and hemibiotrophic plant pathogens; however, the mechanisms by which it exerts its prophylactic role remain unknown. In an attempt to obtain unique insights into the mode of action of Si, we conducted a full comparative transcriptomic analysis of soybean (Glycine max) plants and Phytophthora sojae, a hemibiotroph that relies heavily on effectors for its virulence.

RESULTS: Supplying Si to inoculated plants provided a strong protection against P. sojae over the course of the experiment (21 day). Our results showed that the response of Si-free (Si-) plants to inoculation was characterized early (4 dpi) by a high expression of defense-related genes, including plant receptors, which receded over time as the pathogen progressed into the roots. The infection was synchronized with a high expression of effectors by P. sojae, the nature of which changed over time. By contrast, the transcriptomic response of Si-fed (Si+) plants was remarkably unaffected by the presence of P. sojae, and the expression of effector-coding genes by the pathogen was significantly reduced.

CONCLUSION: Given that the apoplast is a key site of interaction between effectors and plant defenses and receptors in the soybean-P. sojae complex, as well as the site of amorphous-Si accumulation, our results indicate that Si likely interferes with the signaling network between P. sojae and the plant, preventing or decreasing the release of effectors reaching plant receptors, thus creating a form of incompatible interaction.}, } @article {pmid29848301, year = {2018}, author = {Frølich, L and Andersen, TS and Mørup, M}, title = {Rigorous optimisation of multilinear discriminant analysis with Tucker and PARAFAC structures.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {197}, pmid = {29848301}, issn = {1471-2105}, abstract = {BACKGROUND: We propose rigorously optimised supervised feature extraction methods for multilinear data based on Multilinear Discriminant Analysis (MDA) and demonstrate their usage on Electroencephalography (EEG) and simulated data. While existing MDA methods use heuristic optimisation procedures based on an ambiguous Tucker structure, we propose a rigorous approach via optimisation on the cross-product of Stiefel manifolds. We also introduce MDA methods with the PARAFAC structure. We compare the proposed approaches to existing MDA methods and unsupervised multilinear decompositions.

RESULTS: We find that manifold optimisation substantially improves MDA objective functions relative to existing methods and on simulated data in general improve classification performance. However, we find similar classification performance when applied to the electroencephalography data. Furthermore, supervised approaches substantially outperform unsupervised mulitilinear methods whereas methods with the PARAFAC structure perform similarly to those with Tucker structures. Notably, despite applying the MDA procedures to raw Brain-Computer Interface data, their performances are on par with results employing ample pre-processing and they extract discriminatory patterns similar to the brain activity known to be elicited in the investigated EEG paradigms.

CONCLUSION: The proposed usage of manifold optimisation constitutes the first rigorous and monotonous optimisation approach for MDA methods and allows for MDA with the PARAFAC structure. Our results show that MDA methods applied to raw EEG data can extract discriminatory patterns when compared to traditional unsupervised multilinear feature extraction approaches, whereas the proposed PARAFAC structured MDA models provide meaningful patterns of activity.}, } @article {pmid29848299, year = {2018}, author = {Weber, M and Wunderer, J and Lengerer, B and Pjeta, R and Rodrigues, M and Schärer, L and Ladurner, P and Ramm, SA}, title = {A targeted in situ hybridization screen identifies putative seminal fluid proteins in a simultaneously hermaphroditic flatworm.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {81}, pmid = {29848299}, issn = {1471-2148}, support = {RA 2468/1-1//Deutsche Forschungsgemeinschaft/International ; P25404-B25//Austrian Science Fund/International ; 31003A-127503//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; 31003A-143732//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; }, mesh = {Animals ; Female ; Gene Expression Regulation ; Gene Ontology ; Hermaphroditic Organisms/genetics/*metabolism ; In Situ Hybridization/*methods ; Insect Proteins/genetics ; Male ; Organ Specificity ; Phenotype ; Platyhelminths/genetics/*metabolism ; Prostate/metabolism ; RNA, Messenger/genetics/metabolism ; Reproduction ; Seminal Plasma Proteins/*metabolism ; Spermatozoa/metabolism ; }, abstract = {BACKGROUND: Along with sperm, in many taxa ejaculates also contain large numbers of seminal fluid proteins (SFPs). SFPs and sperm are transferred to the mating partner, where they are thought to play key roles in mediating post-mating sexual selection. They modulate the partner's behavior and physiology in ways that influence the reproductive success of both partners, thus potentially leading to sexual conflict. Despite the presumed general functional and evolutionary significance of SFPs, their identification and characterization has to date focused on just a few animal groups, predominantly insects and mammals. Moreover, until now seminal fluid profiling has mainly focused on species with separate sexes. Here we report a comprehensive screen for putative SFPs in the simultaneously hermaphroditic flatworm Macrostomum lignano.

RESULTS: Based on existing transcriptomic data, we selected 150 transcripts known to be (a) predominantly expressed in the tail region of the worms, where the seminal fluid-producing prostate gland cells are located, and (b) differentially expressed in social environments differing in sperm competition level, strongly implying that they represent a phenotypically plastic aspect of male reproductive allocation in this species. For these SFP candidates, we then performed whole-mount in situ hybridization (ISH) experiments to characterize tissue-specific expression. In total, we identified 98 transcripts that exhibited prostate-specific expression, 76 of which we found to be expressed exclusively in the prostate gland cells; additional sites of expression for the remaining 22 included the testis or other gland cells. Bioinformatics analyses of the prostate-limited candidates revealed that at least 64 are predicted to be secretory proteins, making these especially strong candidates to be SFPs that are transferred during copulation.

CONCLUSIONS: Our study represents a first comprehensive analysis using a combination of transcriptomic and ISH screen data to identify SFPs based on transcript expression in seminal fluid-producing tissues. We thereby extend the range of taxa for which seminal fluid has been characterized to a flatworm species with a sequenced genome and for which several methods such as antibody staining, transgenesis and RNA interference have been established. Our data provide a basis for testing the functional and evolutionary significance of SFPs.}, } @article {pmid29848293, year = {2018}, author = {Segal, MR and Bengtsson, HL}, title = {Improved accuracy assessment for 3D genome reconstructions.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {196}, pmid = {29848293}, issn = {1471-2105}, support = {R01 GM109457/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Three dimensional (3D) genome spatial organization is critical for numerous cellular functions, including transcription, while certain conformation-driven structural alterations are frequently oncogenic. Genome conformation had been difficult to elucidate but the advent chromatin conformation capture assays, notably Hi-C, has transformed understanding of chromatin architecture and yielded numerous biological insights. Although most of these findings have flowed from analysis of proximity data produced by these assays, added value in generating 3D reconstructions has been demonstrated, deriving, in part, from superposing genomic features on the reconstruction. However, advantages of 3D structure-based analyses are clearly conditional on the accuracy of the attendant reconstructions, which is difficult to assess. Proponents of competing reconstruction algorithms have evaluated their accuracy by recourse to simulation of toy structures and/or limited fluorescence in situ hybridization (FISH) imaging that features a handful of low resolution probes. Accordingly, new methods of reconstruction accuracy assessment are needed.

RESULTS: Here we utilize two recently devised assays to develop methodology for assessing 3D reconstruction accuracy. Multiplex FISH increases the number of probes by an order of magnitude and hence the number of inter-probe distances by two orders, providing sufficient information for structure-level evaluation via mean-squared deviations (MSD). Crucially, underscoring multiplex FISH applications are large numbers of coordinate-system aligned replicates that provide the basis for a referent distribution for MSD statistics. Using this system we show that reconstructions based on Hi-C data for IMR90 cells are accurate for some chromosomes but not others. The second new assay, genome architecture mapping, utilizes large numbers of thin cryosections to obtain a measure of proximity. We exploit the planarity of the cryosections - not used in inferring proximity - to obtain measures of reconstruction accuracy, with referents provided via resampling. Application to mouse embryonic stem cells shows reconstruction accuracies that vary by chromosome.

CONCLUSIONS: We have developed methods for assessing the accuracy of 3D genome reconstructions that exploit features of recently advanced multiplex FISH and genome architecture mapping assays. These approaches can help overcome the absence of gold standards for making such assessments which are important in view of the considerable uncertainties surrounding 3D genome reconstruction.}, } @article {pmid29848290, year = {2018}, author = {Yin, C and Li, M and Hu, J and Lang, K and Chen, Q and Liu, J and Guo, D and He, K and Dong, Y and Luo, J and Song, Z and Walters, JR and Zhang, W and Li, F and Chen, X}, title = {The genomic features of parasitism, Polyembryony and immune evasion in the endoparasitic wasp Macrocentrus cingulum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {420}, pmid = {29848290}, issn = {1471-2164}, support = {31672033, 31760514//National Natural Science Foundation of China/ ; 2016YFC1200600, 2017YFD0200900, 2017YFC1200602//National Key Research and Development Program/ ; }, mesh = {Animals ; Embryo, Nonmammalian/*embryology ; *Genomics ; Host-Parasite Interactions/*genetics/*immunology ; Immune Evasion/*genetics ; Molecular Sequence Annotation ; Phylogeny ; Wasps/*embryology/*genetics ; }, abstract = {BACKGROUND: Parasitoid wasps are well-known natural enemies of major agricultural pests and arthropod borne diseases. The parasitoid wasp Macrocentrus cingulum (Hymenoptera: Braconidae) has been widely used to control the notorious insect pests Ostrinia furnacalis (Asian Corn Borer) and O. nubilalis (European corn borer). One striking phenomenon exhibited by M. cingulum is polyembryony, the formation of multiple genetically identical offspring from a single zygote. Moreover, M. cingulum employs a passive parasitic strategy by preventing the host's immune system from recognizing the embryo as a foreign body. Thus, the embryos evade the host's immune system and are not encapsulated by host hemocytes. Unfortunately, the mechanism of both polyembryony and immune evasion remains largely unknown.

RESULTS: We report the genome of the parasitoid wasp M. cingulum. Comparative genomics analysis of M. cingulum and other 11 insects were conducted, finding some gene families with apparent expansion or contraction which might be linked to the parasitic behaviors or polyembryony of M. cingulum. Moreover, we present the evidence that the microRNA miR-14b regulates the polyembryonic development of M. cingulum by targeting the c-Myc Promoter-binding Protein 1 (MBP-1), histone-lysine N-methyltransferase 2E (KMT2E) and segmentation protein Runt. In addition, Hemomucin, an O-glycosylated transmembrane protein, protects the endoparasitoid wasp larvae from being encapsulated by host hemocytes. Motif and domain analysis showed that only the hemomucin in two endoparasitoids, M. cingulum and Venturia canescens, possessing the ability of passive immune evasion has intact mucin domain and similar O-glycosylation patterns, indicating that the hemomucin is a key factor modulating the immune evasion.

CONCLUSIONS: The microRNA miR-14b participates in the regulation of polyembryonic development, and the O-glycosylation of the mucin domain in the hemomucin confers the passive immune evasion in this wasp. These key findings provide new insights into the polyembryony and immune evasion.}, } @article {pmid29848288, year = {2018}, author = {Ni, J and Shah, FA and Liu, W and Wang, Q and Wang, D and Zhao, W and Lu, W and Huang, S and Fu, S and Wu, L}, title = {Comparative transcriptome analysis reveals the regulatory networks of cytokinin in promoting the floral feminization in the oil plant Sapium sebiferum.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {96}, pmid = {29848288}, issn = {1471-2229}, support = {1708085QC70//Natural Science Foundation of Anhui Province/ ; YZJJ201619//the President Foundation of Hefei Institutes of Physical Science of Chinese Academy of Sciences/ ; No. kp-2017-21//the key program of 13th five-year plan/ ; KFJ-STS-ZDTP-002//the Science and Technology Service program of Chinese Academy of Sciences/ ; 31500531//National Natural Science Foundation of China/ ; }, mesh = {Benzyl Compounds/pharmacology ; Cytokinins/*pharmacology ; Flowers/drug effects/*genetics/growth & development ; Gene Expression Profiling ; *Gene Regulatory Networks ; Phenylurea Compounds/pharmacology ; Plant Growth Regulators/*pharmacology ; Purines/pharmacology ; Sapium/drug effects/*genetics/growth & development ; Thiadiazoles/pharmacology ; *Transcriptome ; }, abstract = {BACKGROUND: Sapium sebiferum, whose seeds contain high level of fatty acids, has been considered as one of the most important oil plants. However, the high male to female flower ratio limited the seed yield improvement and its industrial potentials. Thus, the study of the sex determination in S. sebiferum is of significant importance in increasing the seed yield.

RESULTS: In this study, we demonstrated that in S. sebiferum, cytokinin (CK) had strong feminization effects on the floral development. Exogenous application with 6-benzylaminopurine (6-BA) or thidiazuron (TDZ) significantly induced the development of female flowers and increased the fruit number. Interestingly, the feminization effects of cytokinin were also detected on the androecious genotype of S. sebiferum which only produce male flowers. To further investigate the mechanism underlying the role of cytokinin in the flower development and sex differentiation, we performed the comparative transcriptome analysis of the floral buds of the androecious plants subjected to 6-BA. The results showed that there were separately 129, 352 and 642 genes differentially expressed at 6 h, 12 h and 24 h after 6-BA treatment. Functional analysis of the differentially expressed genes (DEGs) showed that many genes are related to the hormonal biosynthesis and signaling, nutrients translocation and cell cycle. Moreover, there were twenty one flowering-related genes identified to be differentially regulated by 6-BA treatment. Specifically, the gynoecium development-related genes SPATULA (SPT), KANADI 2 (KAN2), JAGGED (JAG) and Cytochrome P450 78A9 (CYP79A9) were significantly up-regulated, whereas the expression of PISTILLATA (PI), TATA Box Associated Factor II 59 (TAFII59) and MYB Domain Protein 108 (MYB108) that were important for male organ development was down-regulated in response to 6-BA treatment, demonstrating that cytokinin could directly target the floral organ identity genes to regulate the flower sex.

CONCLUSIONS: Our work demonstrated that cytokinin is a potential regulator in female flower development in S. sebiferum. The transcriptome analysis of the floral sex transition from androecious to monoecious in response to cytokinin treatment on the androecious S. sebiferum provided valuable information related to the mechanism of sex determination in the perennial woody plants.}, } @article {pmid29848287, year = {2018}, author = {Bossel Ben-Moshe, N and Gilad, S and Perry, G and Benjamin, S and Balint-Lahat, N and Pavlovsky, A and Halperin, S and Markus, B and Yosepovich, A and Barshack, I and Gal-Yam, EN and Domany, E and Kaufman, B and Dadiani, M}, title = {mRNA-seq whole transcriptome profiling of fresh frozen versus archived fixed tissues.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {419}, pmid = {29848287}, issn = {1471-2164}, support = {3-11175//Ministry of Science and Technology, Israel/ ; R&D fund//Israel National Center for Personalized Medicine/ ; }, mesh = {Breast Neoplasms/genetics/pathology ; *Cryopreservation ; *Gene Expression Profiling ; Humans ; RNA, Messenger/*genetics ; *Sequence Analysis, RNA ; Tissue Fixation/*methods ; }, abstract = {BACKGROUND: The main bottleneck for genomic studies of tumors is the limited availability of fresh frozen (FF) samples collected from patients, coupled with comprehensive long-term clinical follow-up. This shortage could be alleviated by using existing large archives of routinely obtained and stored Formalin-Fixed Paraffin-Embedded (FFPE) tissues. However, since these samples are partially degraded, their RNA sequencing is technically challenging.

RESULTS: In an effort to establish a reliable and practical procedure, we compared three protocols for RNA sequencing using pairs of FF and FFPE samples, both taken from the same breast tumor. In contrast to previous studies, we compared the expression profiles obtained from the two matched sample types, using the same protocol for both. Three protocols were tested on low initial amounts of RNA, as little as 100 ng, to represent the possibly limited availability of clinical samples. For two of the three protocols tested, poly(A) selection (mRNA-seq) and ribosomal-depletion, the total gene expression profiles of matched FF and FFPE pairs were highly correlated. For both protocols, differential gene expression between two FFPE samples was in agreement with their matched FF samples. Notably, although expression levels of FFPE samples by mRNA-seq were mainly represented by the 3'-end of the transcript, they yielded very similar results to those obtained by ribosomal-depletion protocol, which produces uniform coverage across the transcript. Further, focusing on clinically relevant genes, we showed that the high correlation between expression levels persists at higher resolutions.

CONCLUSIONS: Using the poly(A) protocol for FFPE exhibited, unexpectedly, similar efficiency to the ribosomal-depletion protocol, with the latter requiring much higher (2-3 fold) sequencing depth to compensate for the relative low fraction of reads mapped to the transcriptome. The results indicate that standard poly(A)-based RNA sequencing of archived FFPE samples is a reliable and cost-effective alternative for measuring mRNA-seq on FF samples. Expression profiling of FFPE samples by mRNA-seq can facilitate much needed extensive retrospective clinical genomic studies.}, } @article {pmid29848286, year = {2018}, author = {Darbani, B and Kell, DB and Borodina, I}, title = {Energetic evolution of cellular Transportomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {418}, pmid = {29848286}, issn = {1471-2164}, support = {NNF10CC1016517//The Novo Nordisk Foundation Center for Biosustainability/ ; BB/M006891/1, BB/M017702/1 and BB/P009042/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 757384//H2020 European Research Council/ ; }, mesh = {*Energy Metabolism ; *Evolution, Molecular ; *Genomics ; Membrane Transport Proteins/*metabolism ; }, abstract = {BACKGROUND: Transporter proteins mediate the translocation of substances across the membranes of living cells. Many transport processes are energetically expensive and the cells use 20 to 60% of their energy to power the transportomes. We hypothesized that there may be an evolutionary selection pressure for lower energy transporters.

RESULTS: We performed a genome-wide analysis of the compositional reshaping of the transportomes across the kingdoms of bacteria, archaea, and eukarya. We found that the share of ABC transporters is much higher in bacteria and archaea (ca. 27% of the transportome) than in primitive eukaryotes (13%), algae and plants (10%) and in fungi and animals (5-6%). This decrease is compensated by an increased occurrence of secondary transporters and ion channels. The share of ion channels is particularly high in animals (ca. 30% of the transportome) and algae and plants with (ca. 13%), when compared to bacteria and archaea with only 6-7%. Therefore, our results show a move to a preference for the low-energy-demanding transporters (ion channels and carriers) over the more energy-costly transporter classes (ATP-dependent families, and ABCs in particular) as part of the transition from prokaryotes to eukaryotes. The transportome analysis also indicated seven bacterial species, including Neorickettsia risticii and Neorickettsia sennetsu, as likely origins of the mitochondrion in eukaryotes, based on the phylogenetically restricted presence therein of clear homologues of modern mitochondrial solute carriers.

CONCLUSIONS: The results indicate that the transportomes of eukaryotes evolved strongly towards a higher energetic efficiency, as ATP-dependent transporters diminished and secondary transporters and ion channels proliferated. These changes have likely been important in the development of tissues performing energetically costly cellular functions.}, } @article {pmid29848285, year = {2018}, author = {Capra, E and Lazzari, B and Frattini, S and Chessa, S and Coizet, B and Talenti, A and Castiglioni, B and Marsan, PA and Crepaldi, P and Pagnacco, G and Williams, JL and Stella, A}, title = {Distribution of ncRNAs expression across hypothalamic-pituitary-gonadal axis in Capra hircus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {417}, pmid = {29848285}, issn = {1471-2164}, support = {GenHome project "Technological Resort for the advancement of animal genomic research"//Ministero dell'Istruzione, dell'Università e della Ricerca/ ; }, mesh = {Animals ; Female ; *Gene Expression Profiling ; *Goats ; Hypothalamus/*metabolism ; MicroRNAs/genetics ; Ovary/*metabolism ; Pituitary Gland/*metabolism ; RNA, Untranslated/*genetics ; }, abstract = {BACKGROUND: Molecular regulation of the hypothalamic-pituitary-gonadal (HPG) axis plays an essential role in the fine tuning of seasonal estrus in Capra hircus. Noncoding RNAs (ncRNAs) are emerging as key regulators in sexual development and mammalian reproduction. In order to identify ncRNAs and to assess their expression patterns, along the HPG axis, we sequenced ncRNA libraries from hypothalamus, pituitary and ovary of three goats.

RESULTS: Among the medium length noncoding RNAs (mncRNAs) identified, small nucleolar RNAs (snoRNAs) and transfer RNAs (tRNAs) were found to be more abundant in ovary and hypothalamus, respectively. The observed GC content was representative for different classes of ncRNAs, allowing the identification of a tRNA-derived RNA fragments (tRFs) subclass, which had a peak distribution around 32-38% GC content in the hypothalamus. Differences observed among organs confirmed the specificity of microRNA (miRNA) profiles for each organ system.

CONCLUSIONS: Data on ncRNAs in organs constituting the HPG axis will contribute to understanding their role in the physiological regulation of reproduction in goats.}, } @article {pmid29846772, year = {2018}, author = {Danikowski, KM and Cheng, T}, title = {Alkaline Phosphatase Activity of Staphylococcus aureus Grown in Biofilm and Suspension Cultures.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1226-1230}, pmid = {29846772}, issn = {1432-0991}, mesh = {Alkaline Phosphatase/antagonists & inhibitors/*metabolism ; Bacteriological Techniques ; Biofilms/drug effects/*growth & development ; Deoxyribonucleases/pharmacology ; Microbial Sensitivity Tests ; Staphylococcus aureus/drug effects/*enzymology/*physiology ; Vanadates/pharmacology ; }, abstract = {Staphylococcus aureus is known for its resistance to antibiotic treatment as well as the ability to form biofilms. Biofilm formation has been seen in S. aureus infections, yet, the mechanism of biofilm formation is not completely understood. Many molecules, such as DNA and polysaccharides, have been identified in the biofilm microenvironment, but little is known about the enzymes involved in the process. In this paper, alkaline phosphatase (ALP) activity was investigated in S. aureus grown either in biofilm or suspension cultures, achieved using DNase I. A significant increase of ALP activity was observed in S. aureus biofilm culture compared to its suspension counterpart. Treatment of sodium orthovanadate, an ALP inhibitor, significantly decreased biofilm formation. Its inhibition was on par with DNase I treatment at specific doses. Thus, ALP may play an important role in the biofilm formation. Likewise, ALP inhibition may be a novel target for anti-biofilm therapeutics.}, } @article {pmid29846694, year = {2018}, author = {Diwan, GD and Agashe, D}, title = {Wobbling Forth and Drifting Back: The Evolutionary History and Impact of Bacterial tRNA Modifications.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2046-2059}, pmid = {29846694}, issn = {1537-1719}, abstract = {Along with tRNAs, enzymes that modify anticodon bases are a key aspect of translation across the tree of life. tRNA modifications extend wobble pairing, allowing specific ("target") tRNAs to recognize multiple codons and cover for other ("nontarget") tRNAs, often improving translation efficiency and accuracy. However, the detailed evolutionary history and impact of tRNA modifying enzymes has not been analyzed. Using ancestral reconstruction of five tRNA modifications across 1093 bacteria, we show that most modifications were ancestral to eubacteria, but were repeatedly lost in many lineages. Most modification losses coincided with evolutionary shifts in nontarget tRNAs, often driven by increased bias in genomic GC and associated codon use, or by genome reduction. In turn, the loss of tRNA modifications stabilized otherwise highly dynamic tRNA gene repertoires. Our work thus traces the complex history of bacterial tRNA modifications, providing the first clear evidence for their role in the evolution of bacterial translation.}, } @article {pmid29846678, year = {2018}, author = {Patel, R and Scheinfeldt, LB and Sanderford, MD and Lanham, TR and Tamura, K and Platt, A and Glicksberg, BS and Xu, K and Dudley, JT and Kumar, S}, title = {Adaptive Landscape of Protein Variation in Human Exomes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2015-2025}, pmid = {29846678}, issn = {1537-1719}, support = {R01 DK098242/DK/NIDDK NIH HHS/United States ; R01 HG008146/HG/NHGRI NIH HHS/United States ; R01 LM012487/LM/NLM NIH HHS/United States ; }, abstract = {The human genome contains hundreds of thousands of missense mutations. However, only a handful of these variants are known to be adaptive, which implies that adaptation through protein sequence change is an extremely rare phenomenon in human evolution. Alternatively, existing methods may lack the power to pinpoint adaptive variation. We have developed and applied an Evolutionary Probability Approach (EPA) to discover candidate adaptive polymorphisms (CAPs) through the discordance between allelic evolutionary probabilities and their observed frequencies in human populations. EPA reveals thousands of missense CAPs, which suggest that a large number of previously optimal alleles experienced a reversal of fortune in the human lineage. We explored nonadaptive mechanisms to explain CAPs, including the effects of demography, mutation rate variability, and negative and positive selective pressures in modern humans. Many nonadaptive hypotheses were tested, but failed to explain the data, which suggests that a large proportion of CAP alleles have increased in frequency due to beneficial selection. This suggestion is supported by the fact that a vast majority of adaptive missense variants discovered previously in humans are CAPs, and hundreds of CAP alleles are protective in genotype-phenotype association data. Our integrated phylogenomic and population genetic EPA approach predicts the existence of thousands of nonneutral candidate variants in the human proteome. We expect this collection to be enriched in beneficial variation. The EPA approach can be applied to discover candidate adaptive variation in any protein, population, or species for which allele frequency data and reliable multispecies alignments are available.}, } @article {pmid29846663, year = {2018}, author = {Vijay, N and Park, C and Oh, J and Jin, S and Kern, E and Kim, HW and Zhang, J and Park, JK}, title = {Population Genomic Analysis Reveals Contrasting Demographic Changes of Two Closely Related Dolphin Species in the Last Glacial.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2026-2033}, pmid = {29846663}, issn = {1537-1719}, support = {R01 GM120093/GM/NIGMS NIH HHS/United States ; }, abstract = {Population genomic data can be used to infer historical effective population sizes (Ne), which help study the impact of past climate changes on biodiversity. Previous genome sequencing of one individual of the common bottlenose dolphin Tursiops truncatus revealed an unusual, sharp rise in Ne during the last glacial, raising questions about the reliability, generality, underlying cause, and biological implication of this finding. Here we first verify this result by additional sampling of T. truncatus. We then sequence and analyze the genomes of its close relative, the Indo-Pacific bottlenose dolphin T. aduncus. The two species exhibit contrasting demographic changes in the last glacial, likely through actual changes in population size and/or alterations in the level of gene flow among populations. Our findings suggest that even closely related species can have drastically different responses to climatic changes, making predicting the fate of individual species in the ongoing global warming a serious challenge.}, } @article {pmid29846659, year = {2018}, author = {Marin, J and Hedges, SB}, title = {Undersampling Genomes has Biased Time and Rate Estimates Throughout the Tree of Life.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2077-2084}, doi = {10.1093/molbev/msy103}, pmid = {29846659}, issn = {1537-1719}, abstract = {Genomic data drive evolutionary research on the relationships and timescale of life but the genomes of most species remain poorly sampled. Phylogenetic trees can be reconstructed reliably using small data sets and the same has been assumed for the estimation of divergence time with molecular clocks. However, we show here that undersampling of molecular data results in a bias expressed as disproportionately shorter branch lengths and underestimated divergence times in the youngest nodes and branches, termed the small sample artifact. In turn, this leads to increasing speciation and diversification rates towards the present. Any evolutionary analyses derived from these biased branch lengths and speciation rates will be similarly biased. The widely used timetrees of the major species-rich studies of amphibians, birds, mammals, and squamate reptiles are all data-poor and show upswings in diversification rate, suggesting that their results were biased by undersampling. Our results show that greater sampling of genomes is needed for accurate time and rate estimation, which are basic data used in ecological and evolutionary research.}, } @article {pmid29846587, year = {2018}, author = {Žárský, JD and Kohler, TJ and Yde, JC and Falteisek, L and Lamarche-Gagnon, G and Hawkings, JR and Hatton, JE and Stibal, M}, title = {Prokaryotic assemblages in suspended and subglacial sediments within a glacierized catchment on Qeqertarsuaq (Disko Island), west Greenland.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy100}, pmid = {29846587}, issn = {1574-6941}, abstract = {Microbes transported by glacial meltwater streams are thought to be a product of passive dispersal from both supra- and subglacial sources, though studies investigating the origins of these assemblages are scarce. Here, we conducted a survey within a large catchment containing multiple glaciers on Qeqertarsuaq (Disko Island), west Greenland, to investigate whether meltwater-exported microbial assemblages in suspended sediments differ between glacial meltwater streams, and if they reflect corresponding bulk subglacial and extraglacial sediment communities. Using 16S rRNA gene amplicon sequencing, we found proglacial stream assemblages substantially differ from one another, despite their close spatial proximity. Furthermore, proglacial stream assemblages were composed of greater proportions of Cyanobacteria compared to bulk subglacial sediment communities, dominated by Betaproteobacteria, demonstrating large contributions of meltwater and microbial cells from supraglacial habitats. Corresponding physico-chemical characteristics of meltwater suggest that streams draining smaller glaciers had more equal contributions of both supra- and subglacial inputs compared with the main catchment outlet, aligning with observed changes in assemblage structure, such as the decreased proportion of Cyanobacteria. These results suggest that glacier size and hydrological drainage systems may influence the structure of exported microbial assemblages, and collectively provide insights into their formation and fate in thiscurrent age of deglaciation.}, } @article {pmid29846574, year = {2018}, author = {Keating, C and Hughes, D and Mahony, T and Cysneiros, D and Ijaz, UZ and Smith, CJ and O'Flaherty, V}, title = {Cold adaptation and replicable microbial community development during long-term low-temperature anaerobic digestion treatment of synthetic sewage.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, pmid = {29846574}, issn = {1574-6941}, abstract = {The development and activity of a cold-adapting microbial community was monitored during low-temperature anaerobic digestion (LtAD) treatment of wastewater. Two replicate hybrid anaerobic sludge bed-fixed-film reactors treated a synthetic sewage wastewater at 12°C, at organic loading rates of 0.25-1.0 kg chemical oxygen demand (COD) m-3 d-1, over 889 days. The inoculum was obtained from a full-scale anaerobic digestion reactor, which was operated at 37°C. Both LtAD reactors readily degraded the influent with COD removal efficiencies regularly exceeding 78% for both the total and soluble COD fractions. The biomass from both reactors was sampled temporally and tested for activity against hydrolytic and methanogenic substrates at 12°C and 37°C. Data indicated that significantly enhanced low-temperature hydrolytic and methanogenic activity developed in both systems. For example, the hydrolysis rate constant (k) at 12°C had increased 20-30-fold by comparison to the inoculum by day 500. Substrate affinity also increased for hydrolytic substrates at low temperature. Next generation sequencing demonstrated that a shift in a community structure occurred over the trial, involving a 1-log-fold change in 25 SEQS (OTU-free approach) from the inoculum. Microbial community structure changes and process performance were replicable in the LtAD reactors.}, } @article {pmid29845724, year = {2018}, author = {Jongepier, E and Kemena, C and Lopez-Ezquerra, A and Belles, X and Bornberg-Bauer, E and Korb, J}, title = {Remodeling of the juvenile hormone pathway through caste-biased gene expression and positive selection along a gradient of termite eusociality.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {5}, pages = {296-304}, doi = {10.1002/jez.b.22805}, pmid = {29845724}, issn = {1552-5015}, abstract = {The evolution of division of labor between sterile and fertile individuals represents one of the major transitions in biological complexity. A fascinating gradient in eusociality evolved among the ancient hemimetabolous insects, ranging from noneusocial cockroaches through the primitively social lower termites-where workers retain the ability to reproduce-to the higher termites, characterized by lifetime commitment to worker sterility. Juvenile hormone (JH) is a prime candidate for the regulation of reproductive division of labor in termites, as it plays a key role in insect postembryonic development and reproduction. We compared the expression of JH pathway genes between workers and queens in two lower termites (Zootermopsis nevadensis and Cryptotermes secundus) and a higher termite (Macrotermes natalensis) to that of analogous nymphs and adult females of the noneusocial cockroach Blattella germanica. JH biosynthesis and metabolism genes ranged from reproductive female-biased expression in the cockroach to predominantly worker-biased expression in the lower termites. Remarkably, the expression profile of JH pathway genes sets the higher termite apart from the two lower termites, as well as the cockroach, indicating that JH signaling has undergone major changes in this eusocial termite. These changes go beyond mere shifts in gene expression between the different castes, as we find evidence for positive selection in several termite JH pathway genes. Thus, remodeling of the JH pathway may have played a major role in termite social evolution, representing a striking case of convergent molecular evolution between the termites and the distantly related social hymenoptera.}, } @article {pmid29845691, year = {2018}, author = {Reim, E and Blesinger, S and Förster, L and Fischer, K}, title = {Successful despite poor flight performance: range expansion is associated with enhanced exploratory behaviour and fast development.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1165-1179}, doi = {10.1111/jeb.13294}, pmid = {29845691}, issn = {1420-9101}, abstract = {Anthropogenic interference forces species to respond to changing environmental conditions. One possible response is dispersal and concomitant range shifts, allowing individuals to escape unfavourable conditions or to track the shifting climate niche. Range expansions depend on both dispersal capacity and the ability to establish populations beyond the former range. We here compare well-established core populations with recently established edge populations in the currently northward expanding butterfly Lycaena tityrus. Edge populations were characterized by shorter development times and smaller size, a higher sensitivity to high temperature and an enhanced exploratory behaviour. The differences between core and edge populations found suggest adaptation to local climates and an enhanced dispersal ability in edge populations. In particular, enhanced exploratory behaviour may be advantageous in all steps of the dispersal process and may have facilitated the current range expansion. This study describes differences associated with a current range expansion, knowledge which might be useful for a better understanding of species responses to environmental change. We further report on variation between males and females in morphology and flight behaviour, with males showing a longer flight endurance and more pronounced exploratory behaviour than females.}, } @article {pmid29845689, year = {2018}, author = {Da-Gloria, P and Hubbe, M and Neves, WA}, title = {Lagoa Santa's contribution to the origins and life of early Americans.}, journal = {Evolutionary anthropology}, volume = {27}, number = {3}, pages = {121-133}, doi = {10.1002/evan.21587}, pmid = {29845689}, issn = {1520-6505}, mesh = {Anthropology, Physical ; Archaeology ; Brazil ; History, Ancient ; Human Migration ; Humans ; Indians, South American/*history ; Paleopathology ; *Skull/anatomy & histology/pathology ; *Tooth/anatomy & histology/pathology ; United States ; }, abstract = {The region of Lagoa Santa, Central-Eastern Brazil, provides an exceptional archeological record about Late Pleistocene/Early Holocene occupation of the Americas. Since the first interventions made by the Danish naturalist Peter Lund in the 19th century, hundreds of human skeletons have been exhumed in the region. These skeletons are complemented by a rich botanic, faunal, technological, and geomorphological archeological record. We explore here the contributions of Lagoa Santa material to the origins and lifestyle of early Americans, providing an historic background. Cranial morphology of Lagoa Santa skeletons allowed the proposition of a model of two biological components for the occupation of the Americas, in which early Americans are morphologically similar to people of African and Australo-Melanesian origin. Furthermore, the archeological record in the region has revealed an intense use of plant resources, a restricted spatial distribution, and the symbolic elaboration of local hunter-gatherers, unveiling a distinct lifestyle compared to early North American populations.}, } @article {pmid29845686, year = {2018}, author = {Lazagabaster, I and Biernat, M}, title = {Live music, bats, BBQ, and science: The 2018 Paleoanthropology Society meetings.}, journal = {Evolutionary anthropology}, volume = {27}, number = {3}, pages = {105-106}, doi = {10.1002/evan.21589}, pmid = {29845686}, issn = {1520-6505}, } @article {pmid29845668, year = {2018}, author = {Duke, H and Heffter, E and Hlubik, S and Ranhorn, K and Wolfhagen, J}, title = {The 83rd Society for American Archaeology meeting: New directions in the archeology of human evolution.}, journal = {Evolutionary anthropology}, volume = {27}, number = {3}, pages = {102-104}, doi = {10.1002/evan.21591}, pmid = {29845668}, issn = {1520-6505}, } @article {pmid29845633, year = {2018}, author = {Rowsey, DM and Heaney, LR and Jansa, SA}, title = {Diversification rates of the "Old Endemic" murine rodents of Luzon Island, Philippines are inconsistent with incumbency effects and ecological opportunity.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13511}, pmid = {29845633}, issn = {1558-5646}, abstract = {Diversity-dependent cladogenesis occurs when a colonizing lineage exhibits increasing interspecific competition as it ecologically diversifies. Repeated colonization of a region by closely related taxa may cause similar effects as species within each lineage compete with one another. This may be particularly relevant for secondary colonists, which could experience limited diversification due to competition with earlier, incumbent colonists over evolutionary time. We tested the hypothesis that an incumbent lineage may diminish the diversification of secondary colonists in two speciose clades of Philippine "Old Endemic" murine rodents-Phloeomyini and Chrotomyini-on the relatively old oceanic island of Luzon. Although phylogenetic analyses confirm the independent, noncontemporaneous colonization of Luzon by the ancestors of these two clades, we found no support for arrested diversification in either. Rather, it appears that diversification of both clades resulted from constant-rate processes that were either uniform or favored the secondary colonists (Chrotomyini), depending on the method used. Our results suggest that ecological incumbency has not played an important role in determining lineage diversification among Luzon murines, despite sympatric occurrence by constituent species within each lineage, and a substantial head start for the primary colonists.}, } @article {pmid29845336, year = {2018}, author = {Marek, A and Pyzik, E and Stępień-Pyśniak, D and Urban-Chmiel, R and Jarosz, ŁS}, title = {Association Between the Methicillin Resistance of Staphylococcus aureus Isolated from Slaughter Poultry, Their Toxin Gene Profiles and Prophage Patterns.}, journal = {Current microbiology}, volume = {75}, number = {10}, pages = {1256-1266}, pmid = {29845336}, issn = {1432-0991}, mesh = {Abattoirs/statistics & numerical data ; Animals ; Anti-Bacterial Agents/*pharmacology ; Chickens ; Enterotoxins/*metabolism ; Methicillin-Resistant Staphylococcus aureus/genetics/*isolation & purification/metabolism/*virology ; Microbial Sensitivity Tests ; Poland ; Poultry Diseases/*microbiology ; Prophages/classification/genetics/*isolation & purification ; Staphylococcal Infections/microbiology/*veterinary ; Turkeys ; }, abstract = {In this work, 85 strains of Staphylococcus aureus were isolated from samples taken from slaughter poultry in Poland. Attempts were made to determine the prophage profile of the strains and to investigate the presence in their genome of genes responsible for the production of five classical enterotoxins (A-E), toxic shock syndrome toxin (TSST-1), exfoliative toxins (ETA and ETB) and staphylokinase (SAK). For this purpose, multiplex PCR was performed using primer-specific pairs for targeted genes. The presence of the mecA gene was found in 26 strains (30.6%). The genomes of one of the methicillin-resistant S. aureus (MRSA) strains and two methicillin-sensitive S. aureus (MSSA) strains contained the gene responsible for the production of enterotoxin A. Only one MRSA strain and two MSSA strains showed the presence of the toxic shock syndrome toxin (tst) gene. Only one of the MSSA strains had the gene (eta) responsible for the production of exfoliative toxins A. The presence of the staphylokinase gene (sak) was confirmed in 13 MRSA strains and in 5 MSSA strains. The study results indicated a high prevalence of prophages among the test isolates of Staphylococcus aureus. In all, 15 prophage patterns were observed among the isolates. The presence of 77-like prophages incorporated into bacterial genome was especially often demonstrated. Various authors emphasize the special role of these prophages in the spread of virulence factors (staphylokinase, enterotoxin A) not only within strains of the same species but also between species and even types of bacteria.}, } @article {pmid29844654, year = {2018}, author = {Kubick, N and Brösamle, D and Mickael, ME}, title = {Molecular Evolution and Functional Divergence of the IgLON Family.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318775081}, pmid = {29844654}, issn = {1176-9343}, abstract = {IgLON family is a subgroup of cell adhesion molecules which is known to have diverse roles in neuronal development. IgLONs are characterized by possessing 3 Ig-like C2 domains, which play a part in mediating various cellular interactions. Recently, IgLONs have been shown to be expressed at the blood-brain barrier (BBB). However, our understanding of the genetic divergence patterns and evolutionary rates of these proteins in relation to their functions, in general, and at the BBB, in particular, remains inadequate. In this study, 12 species were explored to shed more light on the phylogenetic origins, structure, functional specificity, and divergence of this family. A total of 40 IgLON genes were identified from vertebrates and invertebrates. The absence of IgLON family genes in Hydra vulgaris and Nematostella vectensis but not in Drosophila melanogaster suggests that this family appeared during the time of divergence of Arthropoda 455 Mya. In general, IgLON genes have been subject to strong positive selection in vertebrates. Our study, based on IgLONs' structural similarity, suggests that they may play a role in the evolutionary changes in the brain anatomy towards complexity including regulating neural growth and BBB permeability. IgLONs' functions seem to be performed through complex interactions on the level of motifs as well as single residues. We identified several IgLON motifs that could be influencing cellular migration and proliferation as well as BBB integrity through interactions with SH3 or integrin. Our motif analysis also revealed that NEGR1 might be involved in MAPK pathway as a form of a signal transmitting receptor through its motif (KKVRVVVNF). We found several residues that were both positively selected and with highly functional specificity. We also located functional divergent residues that could act as drug targets to regulate BBB permeability. Furthermore, we identified several putative metalloproteinase cleavage sites that support the ectodomain shedding hypothesis of the IgLONs. In conclusion, our results present a bridge between IgLONs' molecular evolution and their functions.}, } @article {pmid29844615, year = {2018}, author = {Schaid, DJ and Chen, W and Larson, NB}, title = {From genome-wide associations to candidate causal variants by statistical fine-mapping.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {491-504}, pmid = {29844615}, issn = {1471-0064}, support = {R01 GM065450/GM/NIGMS NIH HHS/United States ; }, abstract = {Advancing from statistical associations of complex traits with genetic markers to understanding the functional genetic variants that influence traits is often a complex process. Fine-mapping can select and prioritize genetic variants for further study, yet the multitude of analytical strategies and study designs makes it challenging to choose an optimal approach. We review the strengths and weaknesses of different fine-mapping approaches, emphasizing the main factors that affect performance. Topics include interpreting results from genome-wide association studies (GWAS), the role of linkage disequilibrium, statistical fine-mapping approaches, trans-ethnic studies, genomic annotation and data integration, and other analysis and design issues.}, } @article {pmid29844564, year = {2018}, author = {}, title = {Stem-cell tests must show success.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {611-612}, doi = {10.1038/d41586-018-05284-w}, pmid = {29844564}, issn = {1476-4687}, mesh = {*Stem Cell Transplantation ; }, } @article {pmid29844563, year = {2018}, author = {Cyranoski, D}, title = {'Reprogrammed' stem cells approved to mend human hearts for the first time.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {619-620}, doi = {10.1038/d41586-018-05278-8}, pmid = {29844563}, issn = {1476-4687}, mesh = {Cardiology/*legislation & jurisprudence/*methods ; *Cellular Reprogramming ; Clinical Trials as Topic ; Heart Diseases/pathology/surgery/*therapy ; Humans ; Induced Pluripotent Stem Cells/*cytology/*transplantation ; Japan ; Pilot Projects ; Regeneration ; Regenerative Medicine/*legislation & jurisprudence/methods ; Reproducibility of Results ; Uncertainty ; }, } @article {pmid29844562, year = {2018}, author = {}, title = {Brexit uncertainty threatens fusion-energy research.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {611}, doi = {10.1038/d41586-018-05283-x}, pmid = {29844562}, issn = {1476-4687}, } @article {pmid29844557, year = {2018}, author = {O'Meara, S}, title = {The zest of Zhejiang.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S53}, doi = {10.1038/d41586-018-05266-y}, pmid = {29844557}, issn = {1476-4687}, } @article {pmid29844556, year = {2018}, author = {Drew, L}, title = {How the gene behind Huntington's disease could be neutralized.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S39-S41}, doi = {10.1038/d41586-018-05176-z}, pmid = {29844556}, issn = {1476-4687}, mesh = {Animals ; Brain/drug effects/metabolism ; Clinical Trials as Topic ; Disease Progression ; Female ; Gene Silencing/*drug effects ; Hope ; Humans ; Huntingtin Protein/*analysis/biosynthesis/*genetics/metabolism ; Huntington Disease/*genetics/*therapy ; Macaca mulatta ; Male ; Mutant Proteins/analysis/biosynthesis/genetics/metabolism ; Oligonucleotides, Antisense/administration & dosage/adverse effects/*pharmacology/*therapeutic use ; RNA, Messenger/genetics/metabolism ; Spinal Puncture ; }, } @article {pmid29844555, year = {2018}, author = {Nowogrodzki, A}, title = {Huntington's disease: 4 big questions.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S48}, doi = {10.1038/d41586-018-05180-3}, pmid = {29844555}, issn = {1476-4687}, mesh = {Animals ; Biomarkers/blood/cerebrospinal fluid ; Clinical Trials as Topic ; Disease Progression ; Gene Editing ; Humans ; Huntingtin Protein/cerebrospinal fluid/genetics/*metabolism ; Huntington Disease/blood/cerebrospinal fluid/*genetics/*therapy ; Mice ; Mutant Proteins/cerebrospinal fluid/genetics/*metabolism ; RNAi Therapeutics ; }, } @article {pmid29844554, year = {2018}, author = {Arney, K}, title = {Improved metrics for Huntington's disease trials.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S46-S47}, doi = {10.1038/d41586-018-05179-w}, pmid = {29844554}, issn = {1476-4687}, mesh = {Biomarkers/cerebrospinal fluid ; Clinical Trials as Topic/*methods ; Disease Progression ; *Endpoint Determination ; Humans ; Huntington Disease/*cerebrospinal fluid/genetics/physiopathology/*therapy ; *Molecular Targeted Therapy ; Oligonucleotides, Antisense/pharmacology/therapeutic use ; Piperidines/therapeutic use ; Placebo Effect ; }, } @article {pmid29844553, year = {2018}, author = {Dolgin, E}, title = {When Huntington's disease comes early.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S44-S45}, doi = {10.1038/d41586-018-05178-x}, pmid = {29844553}, issn = {1476-4687}, mesh = {Adolescent ; Adult ; Age Distribution ; Age of Onset ; Aged ; Animals ; Child ; Disease Models, Animal ; Female ; Humans ; Huntington Disease/*genetics/pathology/*physiopathology/therapy ; Magnetic Resonance Imaging ; Mice ; Middle Aged ; Trinucleotide Repeat Expansion ; Young Adult ; }, } @article {pmid29844552, year = {2018}, author = {DeWeerdt, S}, title = {Piecing together the puzzle of Huntington's disease.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S36-S37}, doi = {10.1038/d41586-018-05174-1}, pmid = {29844552}, issn = {1476-4687}, mesh = {Animals ; *Biomedical Research ; Exons/genetics ; Humans ; Huntingtin Protein/genetics/metabolism ; Huntington Disease/genetics/*metabolism/pathology ; Trinucleotide Repeat Expansion ; }, } @article {pmid29844551, year = {2018}, author = {Roach, S}, title = {Living under the shadow of Huntington's disease.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S38}, doi = {10.1038/d41586-018-05175-0}, pmid = {29844551}, issn = {1476-4687}, mesh = {Adult ; Female ; *Genetic Counseling ; *Health Knowledge, Attitudes, Practice ; Heredity ; Humans ; Huntington Disease/*diagnosis/*genetics/psychology ; Male ; *Preimplantation Diagnosis/economics ; Reproductive Medicine/economics ; Young Adult ; }, } @article {pmid29844550, year = {2018}, author = {Brody, H}, title = {Huntington's disease.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S35}, doi = {10.1038/d41586-018-05173-2}, pmid = {29844550}, issn = {1476-4687}, } @article {pmid29844549, year = {2018}, author = {Eisenstein, M}, title = {CRISPR takes on Huntington's disease.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {S42-S43}, doi = {10.1038/d41586-018-05177-y}, pmid = {29844549}, issn = {1476-4687}, mesh = {Animals ; CRISPR-Cas Systems/*genetics ; Disease Models, Animal ; *Gene Editing ; Genetic Therapy/*methods ; Humans ; Huntingtin Protein/*genetics ; Huntington Disease/*genetics/*therapy ; Mice ; Mice, Knockout ; RNAi Therapeutics ; Trinucleotide Repeat Expansion/genetics ; }, } @article {pmid29844548, year = {2018}, author = {Hodapp, T and Brown, E}, title = {Making physics more inclusive.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {629-632}, doi = {10.1038/d41586-018-05260-4}, pmid = {29844548}, issn = {1476-4687}, } @article {pmid29844547, year = {2018}, author = {Arnold, C}, title = {Money for nothing: the truth about universal basic income.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {626-628}, doi = {10.1038/d41586-018-05259-x}, pmid = {29844547}, issn = {1476-4687}, mesh = {History, 20th Century ; History, 21st Century ; Humans ; *Income ; Kenya ; Poverty/*economics/*prevention & control ; Randomized Controlled Trials as Topic ; *Social Welfare/economics/history/trends ; }, } @article {pmid29844546, year = {2018}, author = {Wood, RD}, title = {Fifty years since DNA repair was linked to cancer.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {648-649}, doi = {10.1038/d41586-018-05255-1}, pmid = {29844546}, issn = {1476-4687}, mesh = {DNA Damage ; *DNA Repair ; Humans ; *Neoplasms ; }, } @article {pmid29844545, year = {2018}, author = {Ledford, H}, title = {Rush to protect lucrative antibody patents kicks into gear.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {623-624}, doi = {10.1038/d41586-018-05273-z}, pmid = {29844545}, issn = {1476-4687}, mesh = {Antibodies/chemistry/*immunology/pharmacology/therapeutic use ; Biotechnology/economics/legislation & jurisprudence ; Humans ; Models, Molecular ; Patents as Topic/*legislation & jurisprudence ; Proprotein Convertase 9/antagonists & inhibitors/chemistry/*immunology ; United States ; Universities/economics/legislation & jurisprudence ; }, } @article {pmid29844544, year = {2018}, author = {Gibney, E}, title = {Muons: the little-known particles helping to probe the impenetrable.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {620-621}, doi = {10.1038/d41586-018-05254-2}, pmid = {29844544}, issn = {1476-4687}, } @article {pmid29844543, year = {2018}, author = {Guglielmi, G}, title = {Share of African American men going into medicine hits historic low.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {621-622}, doi = {10.1038/d41586-018-05203-z}, pmid = {29844543}, issn = {1476-4687}, mesh = {African Americans/education/*statistics & numerical data ; *Education, Medical ; Female ; Health Workforce/*statistics & numerical data/trends ; Humans ; Male ; *Medicine ; Mentoring ; Minority Groups/education/statistics & numerical data ; Physicians/*supply & distribution ; Racism/prevention & control/statistics & numerical data ; Science ; Sex Distribution ; Sex Factors ; }, } @article {pmid29844433, year = {2018}, author = {Xu, Q and Liu, ZJ}, title = {The genomic floral language of rose.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {770-771}, doi = {10.1038/s41588-018-0141-9}, pmid = {29844433}, issn = {1546-1718}, } @article {pmid29844432, year = {2018}, author = {}, title = {A rose on the garden fair.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {769}, doi = {10.1038/s41588-018-0146-4}, pmid = {29844432}, issn = {1546-1718}, } @article {pmid29844196, year = {2018}, author = {Blanc, F and Isabet, T and Benisty, H and Sweeney, HL and Cecchini, M and Houdusse, A}, title = {An intermediate along the recovery stroke of myosin VI revealed by X-ray crystallography and molecular dynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6213-6218}, doi = {10.1073/pnas.1711512115}, pmid = {29844196}, issn = {1091-6490}, support = {R01 DC009100/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Crystallography, X-Ray ; Molecular Dynamics Simulation ; Myosin Heavy Chains/*chemistry/*metabolism ; Recombinant Proteins/chemistry/metabolism ; Swine ; Thermodynamics ; }, abstract = {Myosins form a class of actin-based, ATPase motor proteins that mediate important cellular functions such as cargo transport and cell motility. Their functional cycle involves two large-scale swings of the lever arm: the force-generating powerstroke, which takes place on actin, and the recovery stroke during which the lever arm is reprimed into an armed configuration. Previous analyses of the prerecovery (postrigor) and postrecovery (prepowerstroke) states predicted that closure of switch II in the ATP binding site precedes the movement of the converter and the lever arm. Here, we report on a crystal structure of myosin VI, called pretransition state (PTS), which was solved at 2.2 Å resolution. Structural analysis and all-atom molecular dynamics simulations are consistent with PTS being an intermediate along the recovery stroke, where the Relay/SH1 elements adopt a postrecovery conformation, and switch II remains open. In this state, the converter appears to be largely uncoupled from the motor domain and explores an ensemble of partially reprimed configurations through extensive, reversible fluctuations. Moreover, we found that the free energy cost of hydrogen-bonding switch II to ATP is lowered by more than 10 kcal/mol compared with the prerecovery state. These results support the conclusion that closing of switch II does not initiate the recovery stroke transition in myosin VI. Rather, they suggest a mechanism in which lever arm repriming would be mostly driven by thermal fluctuations and eventually stabilized by the switch II interaction with the nucleotide in a ratchet-like fashion.}, } @article {pmid29844195, year = {2018}, author = {Hosoda, Y and Yoshikawa, M and Miyake, M and Tabara, Y and Ahn, J and Woo, SJ and Honda, S and Sakurada, Y and Shiragami, C and Nakanishi, H and Oishi, A and Ooto, S and Miki, A and , and Iida, T and Iijima, H and Nakamura, M and Khor, CC and Wong, TY and Song, K and Park, KH and Yamada, R and Matsuda, F and Tsujikawa, A and Yamashiro, K}, title = {CFH and VIPR2 as susceptibility loci in choroidal thickness and pachychoroid disease central serous chorioretinopathy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6261-6266}, pmid = {29844195}, issn = {1091-6490}, mesh = {Alleles ; Case-Control Studies ; Central Serous Chorioretinopathy/*pathology ; Choroid/*pathology ; Complement Factor H/*genetics ; Genetic Predisposition to Disease/*genetics ; Genome-Wide Association Study/methods ; Humans ; Macular Degeneration/genetics/pathology ; Middle Aged ; Polymorphism, Single Nucleotide/*genetics ; Receptors, Vasoactive Intestinal Peptide, Type II/*genetics ; }, abstract = {Central serous chorioretinopathy (CSC) is a common disease affecting younger people and may lead to vision loss. CSC shares phenotypic overlap with age-related macular degeneration (AMD). As recent studies have revealed a characteristic increase of choroidal thickness in CSC, we conducted a genome-wide association study on choroidal thickness in 3,418 individuals followed by TaqMan assays in 2,692 subjects, and we identified two susceptibility loci: CFH rs800292, an established AMD susceptibility polymorphism, and VIPR2 rs3793217 (P = 2.05 × 10-10 and 6.75 × 10-8, respectively). Case-control studies using patients with CSC confirmed associations between both polymorphisms and CSC (P = 5.27 × 10-5 and 5.14 × 10-5, respectively). The CFH rs800292 G allele is reportedly a risk allele for AMD, whereas the A allele conferred risk for thicker choroid and CSC development. This study not only shows that susceptibility genes for CSC could be discovered using choroidal thickness as a defining variable but also, deepens the understanding of differences between CSC and AMD pathophysiology.}, } @article {pmid29844194, year = {2018}, author = {Khesin, B and Misiolek, G and Modin, K}, title = {Geometric hydrodynamics via Madelung transform.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6165-6170}, doi = {10.1073/pnas.1719346115}, pmid = {29844194}, issn = {1091-6490}, abstract = {We introduce a geometric framework to study Newton's equations on infinite-dimensional configuration spaces of diffeomorphisms and smooth probability densities. It turns out that several important partial differential equations of hydrodynamical origin can be described in this framework in a natural way. In particular, the Madelung transform between the Schrödinger equation and Newton's equations is a symplectomorphism of the corresponding phase spaces. Furthermore, the Madelung transform turns out to be a Kähler map when the space of densities is equipped with the Fisher-Rao information metric. We describe several dynamical applications of these results.}, } @article {pmid29844193, year = {2018}, author = {de Jonge, R and Ebert, MK and Huitt-Roehl, CR and Pal, P and Suttle, JC and Spanner, RE and Neubauer, JD and Jurick, WM and Stott, KA and Secor, GA and Thomma, BPHJ and Van de Peer, Y and Townsend, CA and Bolton, MD}, title = {Gene cluster conservation provides insight into cercosporin biosynthesis and extends production to the genus Colletotrichum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5459-E5466}, pmid = {29844193}, issn = {1091-6490}, support = {R01 ES001670/ES/NIEHS NIH HHS/United States ; T32 GM080189/GM/NIGMS NIH HHS/United States ; }, mesh = {Colletotrichum/*genetics ; DNA, Fungal/genetics ; Fungal Proteins/genetics ; Genes, Fungal/*genetics ; Malus/microbiology ; Multigene Family/*genetics ; Perylene/*analogs & derivatives/metabolism ; Plant Diseases/microbiology ; }, abstract = {Species in the genus Cercospora cause economically devastating diseases in sugar beet, maize, rice, soy bean, and other major food crops. Here, we sequenced the genome of the sugar beet pathogen Cercospora beticola and found it encodes 63 putative secondary metabolite gene clusters, including the cercosporin toxin biosynthesis (CTB) cluster. We show that the CTB gene cluster has experienced multiple duplications and horizontal transfers across a spectrum of plant pathogenic fungi, including the wide-host range Colletotrichum genus as well as the rice pathogen Magnaporthe oryzae Although cercosporin biosynthesis has been thought to rely on an eight-gene CTB cluster, our phylogenomic analysis revealed gene collinearity adjacent to the established cluster in all CTB cluster-harboring species. We demonstrate that the CTB cluster is larger than previously recognized and includes cercosporin facilitator protein, previously shown to be involved with cercosporin autoresistance, and four additional genes required for cercosporin biosynthesis, including the final pathway enzymes that install the unusual cercosporin methylenedioxy bridge. Lastly, we demonstrate production of cercosporin by Colletotrichum fioriniae, the first known cercosporin producer within this agriculturally important genus. Thus, our results provide insight into the intricate evolution and biology of a toxin critical to agriculture and broaden the production of cercosporin to another fungal genus containing many plant pathogens of important crops worldwide.}, } @article {pmid29844192, year = {2018}, author = {Ravindran, S}, title = {QnAs with Rafael Radi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6523-6524}, pmid = {29844192}, issn = {1091-6490}, mesh = {Aging/metabolism ; Animals ; Antioxidants/therapeutic use ; Biochemistry/*history ; Chagas Disease/metabolism ; *Free Radicals/chemistry ; History, 20th Century ; History, 21st Century ; Host-Parasite Interactions ; Humans ; Motor Neurons/metabolism ; Neurocognitive Disorders/metabolism/prevention & control ; Nitric Oxide/chemistry ; Oxidation-Reduction ; Peroxynitrous Acid/chemistry ; *Reactive Oxygen Species/chemistry ; Trypanosoma cruzi/physiology ; Universities/history ; Uruguay ; }, } @article {pmid29844191, year = {2018}, author = {Kleiner, M and Dong, X and Hinzke, T and Wippler, J and Thorson, E and Mayer, B and Strous, M}, title = {Metaproteomics method to determine carbon sources and assimilation pathways of species in microbial communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5576-E5584}, doi = {10.1073/pnas.1722325115}, pmid = {29844191}, issn = {1091-6490}, mesh = {Animals ; Carbon/*metabolism ; Carbon Isotopes/metabolism ; Environmental Microbiology ; Isotope Labeling/methods ; Metabolic Networks and Pathways/*physiology ; Microbiota/*physiology ; Proteome/*metabolism ; Proteomics/*methods ; Software ; Symbiosis/physiology ; }, abstract = {Measurements of stable carbon isotope ratios (δ13C) are widely used in biology to address questions regarding food sources and metabolic pathways used by organisms. The analysis of these so-called stable isotope fingerprints (SIFs) for microbes involved in biogeochemical cycling and microbiota of plants and animals has led to major discoveries in environmental microbiology. Currently, obtaining SIFs for microbial communities is challenging as the available methods either only provide low taxonomic resolution, such as the use of lipid biomarkers, or are limited in throughput, such as nanoscale secondary ion MS imaging of single cells. Here we present "direct protein-SIF" and the Calis-p software package (https://sourceforge.net/projects/calis-p/), which enable high-throughput measurements of accurate δ13C values for individual species within a microbial community. We benchmark the method using 20 pure culture microorganisms and show that the method reproducibly provides SIF values consistent with gold-standard bulk measurements performed with an isotope ratio mass spectrometer. Using mock community samples, we demonstrate that SIF values can also be obtained for individual species within a microbial community. Finally, a case study of an obligate bacteria-animal symbiosis shows that direct protein-SIF confirms previous physiological hypotheses and can provide unexpected insights into the symbionts' metabolism. This confirms the usefulness of this approach to accurately determine δ13C values for different species in microbial community samples.}, } @article {pmid29844190, year = {2018}, author = {Györffy, BA and Kun, J and Török, G and Bulyáki, É and Borhegyi, Z and Gulyássy, P and Kis, V and Szocsics, P and Micsonai, A and Matkó, J and Drahos, L and Juhász, G and Kékesi, KA and Kardos, J}, title = {Local apoptotic-like mechanisms underlie complement-mediated synaptic pruning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6303-6308}, pmid = {29844190}, issn = {1091-6490}, mesh = {Aged ; Apoptosis/*physiology ; Complement Activation/physiology ; Complement C1q/*metabolism ; Humans ; Male ; Microglia/metabolism/physiology ; Neurodegenerative Diseases/metabolism/physiopathology ; Neuronal Plasticity/*physiology ; Phagocytosis/physiology ; Proteome/metabolism ; Proteomics/methods ; Synapses/metabolism/*physiology ; }, abstract = {C1q, a member of the immune complement cascade, is implicated in the selective pruning of synapses by microglial phagocytosis. C1q-mediated synapse elimination has been shown to occur during brain development, while increased activation and complement-dependent synapse loss is observed in neurodegenerative diseases. However, the molecular mechanisms underlying C1q-controlled synaptic pruning are mostly unknown. This study addresses distortions in the synaptic proteome leading to C1q-tagged synapses. Our data demonstrated the preferential localization of C1q to the presynapse. Proteomic investigation and pathway analysis of C1q-tagged synaptosomes revealed the presence of apoptotic-like processes in C1q-tagged synapses, which was confirmed experimentally with apoptosis markers. Moreover, the induction of synaptic apoptotic-like mechanisms in a model of sensory deprivation-induced synaptic depression led to elevated C1q levels. Our results unveiled that C1q label-based synaptic pruning is triggered by and directly linked to apoptotic-like processes in the synaptic compartment.}, } @article {pmid29844189, year = {2018}, author = {Qi, J and Li, X and Peng, H and Cook, EM and Dadashian, EL and Wiestner, A and Park, H and Rader, C}, title = {Potent and selective antitumor activity of a T cell-engaging bispecific antibody targeting a membrane-proximal epitope of ROR1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5467-E5476}, doi = {10.1073/pnas.1719905115}, pmid = {29844189}, issn = {1091-6490}, support = {R01 CA181258/CA/NCI NIH HHS/United States ; UL1 TR001114/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Bispecific/*immunology ; Antineoplastic Agents/*immunology ; CD3 Complex/immunology ; Cell Line, Tumor ; Crystallography, X-Ray/methods ; Epitopes/*immunology ; Humans ; Immunotherapy/methods ; Jurkat Cells ; K562 Cells ; Mice ; Rabbits ; Receptor Tyrosine Kinase-like Orphan Receptors/*immunology ; Single-Chain Antibodies/immunology ; T-Lymphocytes, Cytotoxic/*immunology ; Xenograft Model Antitumor Assays/methods ; }, abstract = {T cell-engaging bispecific antibodies (biAbs) present a promising strategy for cancer immunotherapy, and numerous bispecific formats have been developed for retargeting cytolytic T cells toward tumor cells. To explore the therapeutic utility of T cell-engaging biAbs targeting the receptor tyrosine kinase ROR1, which is expressed by tumor cells of various hematologic and solid malignancies, we used a bispecific ROR1 × CD3 scFv-Fc format based on a heterodimeric and aglycosylated Fc domain designed for extended circulatory t1/2 and diminished systemic T cell activation. A diverse panel of ROR1-targeting scFv derived from immune and naïve rabbit antibody repertoires was compared in this bispecific format for target-dependent T cell recruitment and activation. An ROR1-targeting scFv with a membrane-proximal epitope, R11, revealed potent and selective antitumor activity in vitro, in vivo, and ex vivo and emerged as a prime candidate for further preclinical and clinical studies. To elucidate the precise location and engagement of this membrane-proximal epitope, which is conserved between human and mouse ROR1, the 3D structure of scFv R11 in complex with the kringle domain of ROR1 was determined by X-ray crystallography at 1.6-Å resolution.}, } @article {pmid29844188, year = {2018}, author = {Cheng, Y and Yuan, Q and Vergnes, L and Rong, X and Youn, JY and Li, J and Yu, Y and Liu, W and Cai, H and Lin, JD and Tontonoz, P and Hong, C and Reue, K and Wang, CY}, title = {KDM4B protects against obesity and metabolic dysfunction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5566-E5575}, pmid = {29844188}, issn = {1091-6490}, support = {R01 DE016513/DE/NIDCR NIH HHS/United States ; U24 DK092993/DK/NIDDK NIH HHS/United States ; U24 DK076169/DK/NIDDK NIH HHS/United States ; R01 AR063089/AR/NIAMS NIH HHS/United States ; P01 HL028481/HL/NHLBI NIH HHS/United States ; R01 DE024828/DE/NIDCR NIH HHS/United States ; }, mesh = {Adipocytes/metabolism ; Adipogenesis/physiology ; Adipose Tissue/metabolism ; Animals ; Body Weight/physiology ; Diet, High-Fat/adverse effects ; Energy Metabolism/physiology ; Epigenesis, Genetic/physiology ; Insulin Resistance/physiology ; Jumonji Domain-Containing Histone Demethylases/*metabolism ; Lipolysis/physiology ; Metabolic Diseases/*metabolism ; Mice ; Mice, Inbred C57BL ; Obesity/*metabolism ; Oxidation-Reduction ; Thermogenesis/physiology ; }, abstract = {Although significant progress has been made in understanding epigenetic regulation of in vitro adipogenesis, the physiological functions of epigenetic regulators in metabolism and their roles in obesity remain largely elusive. Here, we report that KDM4B (lysine demethylase 4B) in adipose tissues plays a critical role in energy balance, oxidation, lipolysis, and thermogenesis. Loss of KDM4B in mice resulted in obesity associated with reduced energy expenditure and impaired adaptive thermogenesis. Obesity in KDM4B-deficient mice was accompanied by hyperlipidemia, insulin resistance, and pathological changes in the liver and pancreas. Adipocyte-specific deletion of Kdm4b revealed that the adipose tissues were the main sites for KDM4B antiobesity effects. KDM4B directly controlled the expression of multiple metabolic genes, including Ppargc1a and Ppara Collectively, our studies identify KDM4B as an essential epigenetic factor for the regulation of metabolic health and maintaining normal body weight in mice. KDM4B may provide a therapeutic target for treatment of obesity.}, } @article {pmid29844187, year = {2018}, author = {}, title = {Correction for Ponce de León et al., Human bony labyrinth is an indicator of population history and dispersal from Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5429}, doi = {10.1073/pnas.1808125115}, pmid = {29844187}, issn = {1091-6490}, } @article {pmid29844186, year = {2018}, author = {Castro, MC and Han, QC and Carvalho, LR and Victora, CG and França, GVA}, title = {Implications of Zika virus and congenital Zika syndrome for the number of live births in Brazil.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6177-6182}, pmid = {29844186}, issn = {1091-6490}, mesh = {Abortion, Induced/statistics & numerical data ; Brazil/epidemiology ; Epidemics/*statistics & numerical data ; Female ; Humans ; Microcephaly/epidemiology ; Pregnancy ; Pregnancy Outcome/*epidemiology ; *Zika Virus ; Zika Virus Infection/*congenital/*epidemiology ; }, abstract = {An increase in microcephaly, associated with an epidemic of Zika virus (ZIKV) in Brazil, prompted the World Health Organization to declare a Public Health Emergency of International Concern in February 2016. While knowledge on biological and epidemiological aspects of ZIKV has advanced, demographic impacts remain poorly understood. This study uses time-series analysis to assess the impact of ZIKV on births. Data on births, fetal deaths, and hospitalizations due to abortion complications for Brazilian states, from 2010 to 2016, were used. Forecasts for September 2015 to December 2016 showed that 119,095 fewer births than expected were observed, particularly after April 2016 (a reduction significant at 0.05), demonstrating a link between publicity associated with the ZIKV epidemic and the decline in births. No significant changes were observed in fetal death rates. Although no significant increases in hospitalizations were forecasted, after the ZIKV outbreak hospitalizations happened earlier in the gestational period in most states. We argue that postponement of pregnancy and an increase in abortions may have contributed to the decline in births. Also, it is likely that an increase in safe abortions happened, albeit selective by socioeconomic status. Thus, the ZIKV epidemic resulted in a generation of congenital Zika syndrome (CZS) babies that reflect and exacerbate regional and social inequalities. Since ZIKV transmission has declined, it is unlikely that reductions in births will continue. However, the possibility of a new epidemic is real. There is a need to address gaps in reproductive health and rights, and to understand CZS risk to better inform conception decisions.}, } @article {pmid29844185, year = {2018}, author = {Long, B and Bao, JL and Truhlar, DG}, title = {Unimolecular reaction of acetone oxide and its reaction with water in the atmosphere.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6135-6140}, doi = {10.1073/pnas.1804453115}, pmid = {29844185}, issn = {1091-6490}, abstract = {Criegee intermediates (i.e., carbonyl oxides with two radical sites) are known to be important atmospheric reagents; however, our knowledge of their reaction kinetics is still limited. Although experimental methods have been developed to directly measure the reaction rate constants of stabilized Criegee intermediates, the experimental results cover limited temperature ranges and do not completely agree well with one another. Here we investigate the unimolecular reaction of acetone oxide [(CH3)2COO] and its bimolecular reaction with H2O to obtain rate constants with quantitative accuracy comparable to experimental accuracy. We do this by using CCSDT(Q)/CBS//CCSD(T)-F12a/DZ-F12 benchmark results to select and validate exchange-correlation functionals, which are then used for direct dynamics calculations by variational transition state theory with small-curvature tunneling and torsional and high-frequency anharmonicity. We find that tunneling is very significant in the unimolecular reaction of (CH3)2COO and its bimolecular reaction with H2O. We show that the atmospheric lifetimes of (CH3)2COO depend on temperature and that the unimolecular reaction of (CH3)2COO is the dominant decay mode above 240 K, while the (CH3)2COO + SO2 reaction can compete with the corresponding unimolecular reaction below 240 K when the SO2 concentration is 9 × 1010 molecules per cubic centimeter. We also find that experimental results may not be sufficiently accurate for the unimolecular reaction of (CH3)2COO above 310 K. Not only does the present investigation provide insights into the decay of (CH3)2COO in the atmosphere, but it also provides an illustration of how to use theoretical methods to predict quantitative rate constants of medium-sized Criegee intermediates.}, } @article {pmid29844184, year = {2018}, author = {KaramiNejadRanjbar, M and Eckermann, KN and Ahmed, HMM and Sánchez C, HM and Dippel, S and Marshall, JM and Wimmer, EA}, title = {Consequences of resistance evolution in a Cas9-based sex conversion-suppression gene drive for insect pest management.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6189-6194}, pmid = {29844184}, issn = {1091-6490}, mesh = {Animals ; CRISPR-Cas Systems/*genetics ; Ceratitis capitata/genetics ; Drosophila melanogaster/genetics ; *Evolution, Molecular ; Female ; Gene Editing ; Genes, Insect/*genetics ; Male ; Models, Genetic ; Pest Control, Biological/*methods ; Sex Determination Processes/*genetics ; }, abstract = {The use of a site-specific homing-based gene drive for insect pest control has long been discussed, but the easy design of such systems has become possible only with the recent establishment of CRISPR/Cas9 technology. In this respect, novel targets for insect pest management are provided by new discoveries regarding sex determination. Here, we present a model for a suppression gene drive designed to cause an all-male population collapse in an agricultural pest insect. To evaluate the molecular details of such a sex conversion-based suppression gene drive experimentally, we implemented this strategy in Drosophila melanogaster to serve as a safe model organism. We generated a Cas9-based homing gene-drive element targeting the transformer gene and showed its high efficiency for sex conversion from females to males. However, nonhomologous end joining increased the rate of mutagenesis at the target site, which resulted in the emergence of drive-resistant alleles and therefore curbed the gene drive. This confirms previous studies that simple homing CRISPR/Cas9 gene-drive designs will be ineffective. Nevertheless, by performing population dynamics simulations using the parameters we obtained in D. melanogaster and by adjusting the model for the agricultural pest Ceratitis capitata, we were able to identify adequate modifications that could be successfully applied for the management of wild Mediterranean fruit fly populations using our proposed sex conversion-based suppression gene-drive strategy.}, } @article {pmid29844183, year = {2018}, author = {Manning, SW and Griggs, C and Lorentzen, B and Bronk Ramsey, C and Chivall, D and Jull, AJT and Lange, TE}, title = {Fluctuating radiocarbon offsets observed in the southern Levant and implications for archaeological chronology debates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6141-6146}, doi = {10.1073/pnas.1719420115}, pmid = {29844183}, issn = {1091-6490}, abstract = {Considerable work has gone into developing high-precision radiocarbon (14C) chronologies for the southern Levant region during the Late Bronze to Iron Age/early Biblical periods (∼1200-600 BC), but there has been little consideration whether the current standard Northern Hemisphere 14C calibration curve (IntCal13) is appropriate for this region. We measured 14C ages of calendar-dated tree rings from AD 1610 to 1940 from southern Jordan to investigate contemporary 14C levels and to compare these with IntCal13. Our data reveal an average offset of ∼19 14C years, but, more interestingly, this offset seems to vary in importance through time. While relatively small, such an offset has substantial relevance to high-resolution 14C chronologies for the southern Levant, both archaeological and paleoenvironmental. For example, reconsidering two published studies, we find differences, on average, of 60% between the 95.4% probability ranges determined from IntCal13 versus those approximately allowing for the observed offset pattern. Such differences affect, and even potentially undermine, several current archaeological and historical positions and controversies.}, } @article {pmid29844182, year = {2018}, author = {Eilers, Y and Ta, H and Gwosch, KC and Balzarotti, F and Hell, SW}, title = {MINFLUX monitors rapid molecular jumps with superior spatiotemporal resolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6117-6122}, pmid = {29844182}, issn = {1091-6490}, abstract = {Compared with localization schemes solely based on evaluating patterns of molecular emission, the recently introduced single-molecule localization concept called MINFLUX and the fluorescence nanoscopies derived from it require up to orders of magnitude fewer emissions to attain single-digit nanometer resolution. Here, we demonstrate that the lower number of required fluorescence photons enables MINFLUX to detect molecular movements of a few nanometers at a temporal sampling of well below 1 millisecond. Using fluorophores attached to thermally fluctuating DNA strands as model systems, we demonstrate that measurement times as short as 400 microseconds suffice to localize fluorescent molecules with ∼2-nm precision. Such performance is out of reach for popular camera-based localization by centroid calculation of emission diffraction patterns. Since theoretical limits have not been reached, our results show that emerging MINFLUX nanoscopy bears great potential for dissecting the motions of individual (macro)molecules at hitherto-unattained combinations of spatial and temporal resolution.}, } @article {pmid29844181, year = {2018}, author = {Stott, D and Kristiansen, SM and Lichtenberger, A and Raja, R}, title = {Mapping an ancient city with a century of remotely sensed data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5450-E5458}, doi = {10.1073/pnas.1721509115}, pmid = {29844181}, issn = {1091-6490}, abstract = {The rapidly growing global population places cultural heritage at great risk, and the encroachment of modern settlement on archaeological sites means that valuable information about how past societies worked and interacted with the environment is lost. To manage and mitigate these risks, we require knowledge about what has been lost and what remains, so we can actively decide what should be investigated and what should be preserved for the future. Remote sensing provides archaeologists with some of the tools we need to do this. In this paper we explore the application of multitemporal, multisensor data to map features and chart the impacts of urban encroachment on the ancient city of Jerash (in modern Jordan) by combining archives of aerial photography dating back to 1917 with state-of-the-art airborne laser scanning. The combined results revealed details of the water distribution system and the ancient city plan. This demonstrates that by combining historical images with modern aerial and ground-based data we can successfully detect and contextualize these features and thus achieve a better understanding of life in a city in the past. These methods are essential, given that much of the ancient city has been lost to modern development and the historical imagery is often our only source of information.}, } @article {pmid29844180, year = {2018}, author = {Chang, C and Amer, BR and Osipiuk, J and McConnell, SA and Huang, IH and Hsieh, V and Fu, J and Nguyen, HH and Muroski, J and Flores, E and Ogorzalek Loo, RR and Loo, JA and Putkey, JA and Joachimiak, A and Das, A and Clubb, RT and Ton-That, H}, title = {In vitro reconstitution of sortase-catalyzed pilus polymerization reveals structural elements involved in pilin cross-linking.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5477-E5486}, pmid = {29844180}, issn = {1091-6490}, support = {R01 DE025015/DE/NIDCR NIH HHS/United States ; R01 GM103479/GM/NIGMS NIH HHS/United States ; R01 AI052217/AI/NIAID NIH HHS/United States ; T32 GM007185/GM/NIGMS NIH HHS/United States ; R01 DE017382/DE/NIDCR NIH HHS/United States ; HHSN272201700060C/AI/NIAID NIH HHS/United States ; HHSN272201200026C/AI/NIAID NIH HHS/United States ; }, mesh = {Aminoacyltransferases/*metabolism ; Bacterial Proteins/*metabolism ; Catalysis ; Cell Wall/metabolism ; Corynebacterium/*metabolism ; Crystallography, X-Ray/methods ; Cysteine Endopeptidases/*metabolism ; Fimbriae Proteins/*metabolism ; Fimbriae, Bacterial/*metabolism ; Peptidyl Transferases/metabolism ; Polymerization ; }, abstract = {Covalently cross-linked pilus polymers displayed on the cell surface of Gram-positive bacteria are assembled by class C sortase enzymes. These pilus-specific transpeptidases located on the bacterial membrane catalyze a two-step protein ligation reaction, first cleaving the LPXTG motif of one pilin protomer to form an acyl-enzyme intermediate and then joining the terminal Thr to the nucleophilic Lys residue residing within the pilin motif of another pilin protomer. To date, the determinants of class C enzymes that uniquely enable them to construct pili remain unknown. Here, informed by high-resolution crystal structures of corynebacterial pilus-specific sortase (SrtA) and utilizing a structural variant of the enzyme (SrtA2M), whose catalytic pocket has been unmasked by activating mutations, we successfully reconstituted in vitro polymerization of the cognate major pilin (SpaA). Mass spectrometry, electron microscopy, and biochemical experiments authenticated that SrtA2M synthesizes pilus fibers with correct Lys-Thr isopeptide bonds linking individual pilins via a thioacyl intermediate. Structural modeling of the SpaA-SrtA-SpaA polymerization intermediate depicts SrtA2M sandwiched between the N- and C-terminal domains of SpaA harboring the reactive pilin and LPXTG motifs, respectively. Remarkably, the model uncovered a conserved TP(Y/L)XIN(S/T)H signature sequence following the catalytic Cys, in which the alanine substitutions abrogated cross-linking activity but not cleavage of LPXTG. These insights and our evidence that SrtA2M can terminate pilus polymerization by joining the terminal pilin SpaB to SpaA and catalyze ligation of isolated SpaA domains in vitro provide a facile and versatile platform for protein engineering and bio-conjugation that has major implications for biotechnology.}, } @article {pmid29844179, year = {2018}, author = {Kern, JM and Radford, AN}, title = {Experimental evidence for delayed contingent cooperation among wild dwarf mongooses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6255-6260}, doi = {10.1073/pnas.1801000115}, pmid = {29844179}, issn = {1091-6490}, support = {682253//European Research Council/International ; }, mesh = {Animals ; Female ; Grooming/physiology ; Herpestidae/*physiology ; Interpersonal Relations ; Male ; Memory/physiology ; Social Behavior ; Vocalization, Animal ; }, abstract = {Many animals participate in biological markets, with strong evidence existing for immediate cooperative trades. In particular, grooming is often exchanged for itself or other commodities, such as coalitionary support or access to food and mates. More contentious is the possibility that nonhuman animals can rely on memories of recent events, providing contingent cooperation even when there is a temporal delay between two cooperative acts. Here we provide experimental evidence of delayed cross-commodity grooming exchange in wild dwarf mongooses (Helogale parvula). First, we use natural observations and social-network analyses to demonstrate a positive link between grooming and sentinel behavior (acting as a raised guard). Group members who contributed more to sentinel behavior received more grooming and had a better social-network position. We then used a field-based playback experiment to test a causal link between contributions to sentinel behavior and grooming received later in the day. During 3-h trial sessions, the perceived sentinel contributions of a focal individual were either up-regulated (playback of its surveillance calls, which are given naturally during sentinel bouts) or unmanipulated (playback of its foraging close calls as a control). On returning to the sleeping refuge at the end of the day, focal individuals received more grooming following surveillance-call playback than control-call playback and more grooming than a matched individual whose sentinel contributions were not up-regulated. We believe our study therefore provides experimental evidence of delayed contingent cooperation in a wild nonprimate species.}, } @article {pmid29844178, year = {2018}, author = {Kretchmer, JS and Boekelheide, N and Warren, JJ and Winkler, JR and Gray, HB and Miller, TF}, title = {Fluctuating hydrogen-bond networks govern anomalous electron transfer kinetics in a blue copper protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6129-6134}, pmid = {29844178}, issn = {1091-6490}, support = {F32 GM095037/GM/NIGMS NIH HHS/United States ; R01 DK019038/DK/NIDDK NIH HHS/United States ; }, mesh = {Azurin/*chemistry/*metabolism ; Electron Transport ; Hydrogen Bonding ; Kinetics ; Molecular Dynamics Simulation ; Pseudomonas aeruginosa/chemistry/metabolism ; }, abstract = {We combine experimental and computational methods to address the anomalous kinetics of long-range electron transfer (ET) in mutants of Pseudomonas aeruginosa azurin. ET rates and driving forces for wild type (WT) and three N47X mutants (X = L, S, and D) of Ru(2,2'-bipyridine)2 (imidazole)(His83) azurin are reported. An enhanced ET rate for the N47L mutant suggests either an increase of the donor-acceptor (DA) electronic coupling or a decrease in the reorganization energy for the reaction. The underlying atomistic features are investigated using a recently developed nonadiabatic molecular dynamics method to simulate ET in each of the azurin mutants, revealing unexpected aspects of DA electronic coupling. In particular, WT azurin and all studied mutants exhibit more DA compression during ET (>2 Å) than previously recognized. Moreover, it is found that DA compression involves an extended network of hydrogen bonds, the fluctuations of which gate the ET reaction, such that DA compression is facilitated by transiently rupturing hydrogen bonds. It is found that the N47L mutant intrinsically disrupts this hydrogen-bond network, enabling particularly facile DA compression. This work, which reveals the surprisingly fluctional nature of ET in azurin, suggests that hydrogen-bond networks can modulate the efficiency of long-range biological ET.}, } @article {pmid29844177, year = {2018}, author = {Karnahl, M and Park, M and Krause, C and Hiller, U and Mayer, U and Stierhof, YD and Jürgens, G}, title = {Functional diversification of Arabidopsis SEC1-related SM proteins in cytokinetic and secretory membrane fusion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6309-6314}, doi = {10.1073/pnas.1722611115}, pmid = {29844177}, issn = {1091-6490}, mesh = {Arabidopsis/*metabolism ; Arabidopsis Proteins/*metabolism ; Carrier Proteins/metabolism ; Cell Membrane/metabolism/physiology ; Cytokinesis/*physiology ; Membrane Fusion/*physiology ; Munc18 Proteins/metabolism ; Protein Transport/*physiology ; Qa-SNARE Proteins/metabolism ; }, abstract = {Sec1/Munc18 (SM) proteins contribute to membrane fusion by interacting with Qa-SNAREs or nascent trans-SNARE complexes. Gymnosperms and the basal angiosperm Amborella have only a single SEC1 gene related to the KEULE gene in Arabidopsis However, the genomes of most angiosperms including Arabidopsis encode three SEC1-related SM proteins of which only KEULE has been functionally characterized as interacting with the cytokinesis-specific Qa-SNARE KNOLLE during cell-plate formation. Here we analyze the closest paralog of KEULE named SEC1B. In contrast to the cytokinesis defects of keule mutants, sec1b mutants are homozygous viable. However, the keule sec1b double mutant was nearly gametophytically lethal, displaying collapsed pollen grains, which suggests substantial overlap between SEC1B and KEULE functions in secretion-dependent growth. SEC1B had a strong preference for interaction with the evolutionarily ancient Qa-SNARE SYP132 involved in secretion and cytokinesis, whereas KEULE interacted with both KNOLLE and SYP132. This differential interaction with Qa-SNAREs is likely conferred by domains 1 and 2a of the two SM proteins. Comparative analysis of all four possible combinations of the relevant SEC1 Qa-SNARE double mutants revealed that in cytokinesis, the interaction of SEC1B with KNOLLE plays no role, whereas the interaction of KEULE with KNOLLE is prevalent and functionally as important as the interactions of both SEC1B and KEU with SYP132 together. Our results suggest that functional diversification of the two SEC1-related SM proteins during angiosperm evolution resulted in enhanced interaction of SEC1B with Qa-SNARE SYP132, and thus a predominant role of SEC1B in secretion.}, } @article {pmid29844176, year = {2018}, author = {}, title = {Correction for Spence et al., Revealing the specificity of regulatory T cells in murine autoimmune diabetes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5634}, doi = {10.1073/pnas.1808331115}, pmid = {29844176}, issn = {1091-6490}, } @article {pmid29844175, year = {2018}, author = {Karim, H and Kim, SH and Lapato, AS and Yasui, N and Katzenellenbogen, JA and Tiwari-Woodruff, SK}, title = {Increase in chemokine CXCL1 by ERβ ligand treatment is a key mediator in promoting axon myelination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6291-6296}, doi = {10.1073/pnas.1721732115}, pmid = {29844175}, issn = {1091-6490}, support = {R01 NS081141/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/drug effects/metabolism ; Axons/drug effects/*metabolism ; Cells, Cultured ; Central Nervous System/drug effects/metabolism ; Chemokine CXCL1/*metabolism ; Encephalomyelitis, Autoimmune, Experimental/drug therapy ; Estrogen Receptor beta/*metabolism ; Female ; Ligands ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/drug therapy/metabolism ; Myelin Sheath/drug effects/*metabolism ; Oligodendroglia/drug effects/metabolism ; Receptors, Interleukin-8B/metabolism ; }, abstract = {Estrogen receptor β (ERβ) ligands promote remyelination in mouse models of multiple sclerosis. Recent work using experimental autoimmune encephalomyelitis (EAE) has shown that ERβ ligands induce axon remyelination, but impact peripheral inflammation to varying degrees. To identify if ERβ ligands initiate a common immune mechanism in remyelination, central and peripheral immunity and pathology in mice given ERβ ligands at peak EAE were assessed. All ERβ ligands induced differential expression of cytokines and chemokines, but increased levels of CXCL1 in the periphery and in astrocytes. Oligodendrocyte CXCR2 binds CXCL1 and has been implicated in normal myelination. In addition, despite extensive immune cell accumulation in the CNS, all ERβ ligands promoted extensive remyelination in mice at peak EAE. This finding highlights a component of the mechanism by which ERβ ligands mediate remyelination. Hence, interplay between the immune system and central nervous system may be responsible for the remyelinating effects of ERβ ligands. Our findings of potential neuroprotective benefits arising from the presence of CXCL1 could have implications for improved therapies for multiple sclerosis.}, } @article {pmid29844174, year = {2018}, author = {Phillips, PJ and Yates, AN and Hu, Y and Hahn, CA and Noyes, E and Jackson, K and Cavazos, JG and Jeckeln, G and Ranjan, R and Sankaranarayanan, S and Chen, JC and Castillo, CD and Chellappa, R and White, D and O'Toole, AJ}, title = {Face recognition accuracy of forensic examiners, superrecognizers, and face recognition algorithms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6171-6176}, pmid = {29844174}, issn = {1091-6490}, mesh = {*Algorithms ; Biometric Identification/*methods ; Face/*anatomy & histology ; Forensic Sciences/*methods ; Humans ; Machine Learning ; Reproducibility of Results ; }, abstract = {Achieving the upper limits of face identification accuracy in forensic applications can minimize errors that have profound social and personal consequences. Although forensic examiners identify faces in these applications, systematic tests of their accuracy are rare. How can we achieve the most accurate face identification: using people and/or machines working alone or in collaboration? In a comprehensive comparison of face identification by humans and computers, we found that forensic facial examiners, facial reviewers, and superrecognizers were more accurate than fingerprint examiners and students on a challenging face identification test. Individual performance on the test varied widely. On the same test, four deep convolutional neural networks (DCNNs), developed between 2015 and 2017, identified faces within the range of human accuracy. Accuracy of the algorithms increased steadily over time, with the most recent DCNN scoring above the median of the forensic facial examiners. Using crowd-sourcing methods, we fused the judgments of multiple forensic facial examiners by averaging their rating-based identity judgments. Accuracy was substantially better for fused judgments than for individuals working alone. Fusion also served to stabilize performance, boosting the scores of lower-performing individuals and decreasing variability. Single forensic facial examiners fused with the best algorithm were more accurate than the combination of two examiners. Therefore, collaboration among humans and between humans and machines offers tangible benefits to face identification accuracy in important applications. These results offer an evidence-based roadmap for achieving the most accurate face identification possible.}, } @article {pmid29844173, year = {2018}, author = {}, title = {Correction for Nepomnyachiy et al., Complex evolutionary footprints revealed in an analysis of reused protein segments of diverse lengths.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5430}, doi = {10.1073/pnas.1807785115}, pmid = {29844173}, issn = {1091-6490}, } @article {pmid29844172, year = {2018}, author = {Henriques, A and Koliaraki, V and Kollias, G}, title = {Mesenchymal MAPKAPK2/HSP27 drives intestinal carcinogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5546-E5555}, pmid = {29844172}, issn = {1091-6490}, mesh = {Animals ; Apoptosis/physiology ; Carcinogenesis/*metabolism/*pathology ; Cell Proliferation/physiology ; Colitis/metabolism ; Endothelial Cells/metabolism/pathology ; HSP27 Heat-Shock Proteins/*metabolism ; Intestinal Mucosa/*metabolism ; Intestines/*pathology ; Intracellular Signaling Peptides and Proteins/*metabolism ; Mesenchymal Stem Cells/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasm Proteins/metabolism ; Neovascularization, Pathologic/metabolism/pathology ; Phosphorylation/physiology ; Protein-Serine-Threonine Kinases/*metabolism ; Signal Transduction/physiology ; p38 Mitogen-Activated Protein Kinases/metabolism ; }, abstract = {Mesenchymal cells in the microenvironment of cancer exert important functions in tumorigenesis; however, little is known of intrinsic pathways that mediate these effects. MAPK signals, such as from MAPKAPK2 (MK2) are known to modulate tumorigenesis, yet their cell-specific role has not been determined. Here, we studied the cell-specific role of MK2 in intestinal carcinogenesis using complete and conditional ablation of MK2. We show that both genetic and chemical inhibition of MK2 led to decreased epithelial cell proliferation, associated with reduced tumor growth and invasive potential in the Apcmin/+ mouse model. Notably, this function of MK2 was not mediated by its well-described immunomodulatory role in immune cells. Deletion of MK2 in intestinal mesenchymal cells (IMCs) led to both reduced tumor multiplicity and growth. Mechanistically, MK2 in IMCs was required for Hsp27 phosphorylation and the production of downstream tumorigenic effector molecules, dominantly affecting epithelial proliferation, apoptosis, and angiogenesis. Genetic ablation of MK2 in intestinal epithelial or endothelial cells was less effective in comparison with its complete deletion, leading to reduction of tumor size via modulation of epithelial apoptosis and angiogenesis-associated proliferation, respectively. Similar results were obtained in a model of colitis-associated carcinogenesis, indicating a mesenchymal-specific role for MK2 also in this model. Our findings demonstrate the central pathogenic role of mesenchymal-specific MK2/Hsp27 axis in tumorigenesis and highlight the value of mesenchymal MK2 inhibition in the treatment of cancer.}, } @article {pmid29844171, year = {2018}, author = {Berecki, G and Howell, KB and Deerasooriya, YH and Cilio, MR and Oliva, MK and Kaplan, D and Scheffer, IE and Berkovic, SF and Petrou, S}, title = {Dynamic action potential clamp predicts functional separation in mild familial and severe de novo forms of SCN2A epilepsy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5516-E5525}, doi = {10.1073/pnas.1800077115}, pmid = {29844171}, issn = {1091-6490}, mesh = {Action Potentials/*genetics ; Adolescent ; Adult ; Brain Diseases/genetics ; Child ; Child, Preschool ; Epilepsy/*genetics ; Female ; Genetic Association Studies/methods ; Genetic Variation/genetics ; Genotype ; Humans ; Infant ; Infant, Newborn ; Male ; NAV1.2 Voltage-Gated Sodium Channel/*genetics ; Phenotype ; Seizures/genetics ; Spasms, Infantile/genetics ; Young Adult ; }, abstract = {De novo variants in SCN2A developmental and epileptic encephalopathy (DEE) show distinctive genotype-phenotype correlations. The two most recurrent SCN2A variants in DEE, R1882Q and R853Q, are associated with different ages and seizure types at onset. R1882Q presents on day 1 of life with focal seizures, while infantile spasms is the dominant seizure type seen in R853Q cases, presenting at a median age of 8 months. Voltage clamp, which characterizes the functional properties of ion channels, predicted gain-of-function for R1882Q and loss-of-function for R853Q. Dynamic action potential clamp, that we implement here as a method for modeling neurophysiological consequences of a given epilepsy variant, predicted that the R1882Q variant would cause a dramatic increase in firing, whereas the R853Q variant would cause a marked reduction in action potential firing. Dynamic clamp was also able to functionally separate the L1563V variant, seen in benign familial neonatal-infantile seizures from R1882Q, seen in DEE, suggesting a diagnostic potential for this type of analysis. Overall, the study shows a strong correlation between clinical phenotype, SCN2A genotype, and functional modeling. Dynamic clamp is well positioned to impact our understanding of pathomechanisms and for development of disease mechanism-targeted therapies in genetic epilepsy.}, } @article {pmid29844170, year = {2018}, author = {Puno, MR and Lima, CD}, title = {Structural basis for MTR4-ZCCHC8 interactions that stimulate the MTR4 helicase in the nuclear exosome-targeting complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5506-E5515}, pmid = {29844170}, issn = {1091-6490}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 GM079196/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R35 GM118080/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Nucleus/*metabolism ; DEAD-box RNA Helicases/*metabolism ; Exosome Multienzyme Ribonuclease Complex/metabolism ; Exosomes/*metabolism ; Models, Molecular ; Nuclear Proteins/*metabolism ; Protein Binding/physiology ; RNA-Binding Proteins/metabolism ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {The nuclear exosome-targeting (NEXT) complex functions as an RNA exosome cofactor and is involved in surveillance and turnover of aberrant transcripts and noncoding RNAs. NEXT is a ternary complex composed of the RNA-binding protein RBM7, the scaffold zinc-knuckle protein ZCCHC8, and the helicase MTR4. While RNA interactions with RBM7 are known, it remains unclear how NEXT subunits collaborate to recognize and prepare substrates for degradation. Here, we show that MTR4 helicase activity is enhanced when associated with RBM7 and ZCCHC8. While uridine-rich substrates interact with RBM7 and are preferred, optimal activity is observed when substrates include a polyadenylated 3' end. We identify a bipartite interaction of ZCCHC8 with MTR4 and uncover a role for the conserved C-terminal domain of ZCCHC8 in stimulating MTR4 helicase and ATPase activities. A crystal structure reveals that the ZCCHC8 C-terminal domain binds the helicase core in a manner that is distinct from that observed for Saccharomyces cerevisiae exosome cofactors Trf4p and Air2p. Our results are consistent with a model whereby effective targeting of substrates by NEXT entails recognition of elements within the substrate and activation of MTR4 helicase activity.}, } @article {pmid29844169, year = {2018}, author = {Zheng, H and Lu, C and Lan, J and Fan, S and Nanda, V and Xu, F}, title = {How electrostatic networks modulate specificity and stability of collagen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6207-6212}, doi = {10.1073/pnas.1802171115}, pmid = {29844169}, issn = {1091-6490}, mesh = {Collagen/*chemistry/*metabolism ; Humans ; Molecular Dynamics Simulation ; Protein Multimerization ; Protein Stability ; Static Electricity ; Temperature ; }, abstract = {One-quarter of the 28 types of natural collagen exist as heterotrimers. The oligomerization state of collagen affects the structure and mechanics of the extracellular matrix, providing essential cues to modulate biological and pathological processes. A lack of high-resolution structural information limits our mechanistic understanding of collagen heterospecific self-assembly. Here, the 1.77-Å resolution structure of a synthetic heterotrimer demonstrates the balance of intermolecular electrostatics and hydrogen bonding that affects collagen stability and heterospecificity of assembly. Atomistic simulations and mutagenesis based on the solved structure are used to explore the contributions of specific interactions to energetics. A predictive model of collagen stability and specificity is developed for engineering novel collagen structures.}, } @article {pmid29844168, year = {2018}, author = {Dimitrov, S and Gouttefangeas, C and Besedovsky, L and Jensen, ATR and Chandran, PA and Rusch, E and Businger, R and Schindler, M and Lange, T and Born, J and Rammensee, HG}, title = {Activated integrins identify functional antigen-specific CD8+ T cells within minutes after antigen stimulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5536-E5545}, pmid = {29844168}, issn = {1091-6490}, mesh = {Adolescent ; Adoptive Transfer/methods ; Adult ; Antigens/*immunology ; CD18 Antigens/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Humans ; Immunotherapy, Adoptive/methods ; Intercellular Adhesion Molecule-1/immunology ; Lymphocyte Activation/immunology ; Receptors, Antigen, T-Cell/immunology ; Young Adult ; }, abstract = {Immediate β2-integrin activation upon T cell receptor stimulation is critical for effective interaction between T cells and their targets and may therefore be used for the rapid identification and isolation of functional T cells. We present a simple and sensitive flow cytometry-based assay to assess antigen-specific T cells using fluorescent intercellular adhesion molecule (ICAM)-1 multimers that specifically bind to activated β2-integrins. The method is compatible with surface and intracellular staining; it is applicable for monitoring of a broad range of virus-, tumor-, and vaccine-specific CD8+ T cells, and for isolating viable antigen-reacting cells. ICAM-1 binding correlates with peptide-MHC multimer binding but, notably, it identifies the fraction of antigen-specific CD8+ T cells with immediate and high functional capability (i.e., expressing high levels of cytotoxic markers and cytokines). Compared with the currently available methods, staining of activated β2-integrins presents the unique advantage of requiring activation times of only several minutes, therefore delivering functional information nearly reflecting the in vivo situation. Hence, the ICAM-1 assay is most suitable for rapid and precise monitoring of functional antigen-specific T cell responses, including for patient samples in a variety of clinical settings, as well as for the isolation of functional T cells for adoptive cell-transfer immunotherapies.}, } @article {pmid29844167, year = {2018}, author = {Chen, Z and Wu, D and Thomas-Ahner, JM and Lu, C and Zhao, P and Zhang, Q and Geraghty, C and Yan, PS and Hankey, W and Sunkel, B and Cheng, X and Antonarakis, ES and Wang, QE and Liu, Z and Huang, TH and Jin, VX and Clinton, SK and Luo, J and Huang, J and Wang, Q}, title = {Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6810-6815}, pmid = {29844167}, issn = {1091-6490}, support = {R01 CA200853/CA/NCI NIH HHS/United States ; R01 CA205001/CA/NCI NIH HHS/United States ; R50 CA211524/CA/NCI NIH HHS/United States ; R01 GM120221/GM/NIGMS NIH HHS/United States ; R01 CA185297/CA/NCI NIH HHS/United States ; R01 CA212403/CA/NCI NIH HHS/United States ; R01 CA211175/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; R01 CA172603/CA/NCI NIH HHS/United States ; U54 CA217297/CA/NCI NIH HHS/United States ; }, mesh = {*Alternative Splicing ; Cell Line, Tumor ; *Gene Expression Regulation, Neoplastic ; Homeodomain Proteins/genetics/*metabolism ; Humans ; Male ; Neoplasm Proteins/genetics/*metabolism ; Prostatic Neoplasms, Castration-Resistant/genetics/*metabolism ; Protein Binding ; Protein Isoforms/biosynthesis/genetics ; Receptors, Androgen/*biosynthesis/genetics ; *Up-Regulation ; }, abstract = {The constitutively active androgen receptor (AR) splice variant 7 (AR-V7) plays an important role in the progression of castration-resistant prostate cancer (CRPC). Although biomarker studies established the role of AR-V7 in resistance to AR-targeting therapies, how AR-V7 mediates genomic functions in CRPC remains largely unknown. Using a ChIP-exo approach, we show AR-V7 binds to distinct genomic regions and recognizes a full-length androgen-responsive element in CRPC cells and patient tissues. Remarkably, we find dramatic differences in AR-V7 cistromes across diverse CRPC cells and patient tissues, regulating different target gene sets involved in CRPC progression. Surprisingly, we discover that HoxB13 is universally required for and colocalizes with AR-V7 binding to open chromatin across CRPC genomes. HoxB13 pioneers AR-V7 binding through direct physical interaction, and collaborates with AR-V7 to up-regulate target oncogenes. Transcriptional coregulation by HoxB13 and AR-V7 was further supported by their coexpression in tumors and circulating tumor cells from CRPC patients. Importantly, HoxB13 silencing significantly decreases CRPC growth through inhibition of AR-V7 oncogenic function. These results identify HoxB13 as a pivotal upstream regulator of AR-V7-driven transcriptomes that are often cell context-dependent in CRPC, suggesting that HoxB13 may serve as a therapeutic target for AR-V7-driven prostate tumors.}, } @article {pmid29844166, year = {2018}, author = {Colón-González, FJ and Harris, I and Osborn, TJ and Steiner São Bernardo, C and Peres, CA and Hunter, PR and Lake, IR}, title = {Limiting global-mean temperature increase to 1.5-2 °C could reduce the incidence and spatial spread of dengue fever in Latin America.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6243-6248}, doi = {10.1073/pnas.1718945115}, pmid = {29844166}, issn = {1091-6490}, support = {//Department of Health/United Kingdom ; }, mesh = {Carbon Dioxide/chemistry ; Climate Change ; Dengue/*epidemiology/*etiology ; Global Warming ; Humans ; Incidence ; Latin America/epidemiology ; Temperature ; }, abstract = {The Paris Climate Agreement aims to hold global-mean temperature well below 2 °C and to pursue efforts to limit it to 1.5 °C above preindustrial levels. While it is recognized that there are benefits for human health in limiting global warming to 1.5 °C, the magnitude with which those societal benefits will be accrued remains unquantified. Crucial to public health preparedness and response is the understanding and quantification of such impacts at different levels of warming. Using dengue in Latin America as a study case, a climate-driven dengue generalized additive mixed model was developed to predict global warming impacts using five different global circulation models, all scaled to represent multiple global-mean temperature assumptions. We show that policies to limit global warming to 2 °C could reduce dengue cases by about 2.8 (0.8-7.4) million cases per year by the end of the century compared with a no-policy scenario that warms by 3.7 °C. Limiting warming further to 1.5 °C produces an additional drop in cases of about 0.5 (0.2-1.1) million per year. Furthermore, we found that by limiting global warming we can limit the expansion of the disease toward areas where incidence is currently low. We anticipate our study to be a starting point for more comprehensive studies incorporating socioeconomic scenarios and how they may further impact dengue incidence. Our results demonstrate that although future climate change may amplify dengue transmission in the region, impacts may be avoided by constraining the level of warming.}, } @article {pmid29844165, year = {2018}, author = {Leithner, K and Triebl, A and Trötzmüller, M and Hinteregger, B and Leko, P and Wieser, BI and Grasmann, G and Bertsch, AL and Züllig, T and Stacher, E and Valli, A and Prassl, R and Olschewski, A and Harris, AL and Köfeler, HC and Olschewski, H and Hrzenjak, A}, title = {The glycerol backbone of phospholipids derives from noncarbohydrate precursors in starved lung cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6225-6230}, pmid = {29844165}, issn = {1091-6490}, mesh = {A549 Cells ; Animals ; Glucose/metabolism ; Glutamine/metabolism ; Glycerol/*metabolism ; Heterografts ; Humans ; Lactic Acid/metabolism ; Male ; Mice ; Mice, Nude ; Neoplasms/*metabolism ; Phosphoenolpyruvate Carboxykinase (ATP)/genetics/*metabolism ; Phospholipids/chemistry/*metabolism ; }, abstract = {Cancer cells are reprogrammed to consume large amounts of glucose to support anabolic biosynthetic pathways. However, blood perfusion and consequently the supply with glucose are frequently inadequate in solid cancers. PEPCK-M (PCK2), the mitochondrial isoform of phosphoenolpyruvate carboxykinase (PEPCK), has been shown by us and others to be functionally expressed and to mediate gluconeogenesis, the reverse pathway of glycolysis, in different cancer cells. Serine and ribose synthesis have been identified as downstream pathways fed by PEPCK in cancer cells. Here, we report that PEPCK-M-dependent glycerol phosphate formation from noncarbohydrate precursors (glyceroneogenesis) occurs in starved lung cancer cells and supports de novo glycerophospholipid synthesis. Using stable isotope-labeled glutamine and lactate, we show that PEPCK-M generates phosphoenolpyruvate and 3-phosphoglycerate, which are at least partially converted to glycerol phosphate and incorporated into glycerophospholipids (GPL) under glucose and serum starvation. This pathway is required to maintain levels of GPL, especially phosphatidylethanolamine (PE), as shown by stable shRNA-mediated silencing of PEPCK-M in H23 lung cancer cells. PEPCK-M shRNA led to reduced colony formation after starvation, and the effect was partially reversed by the addition of dioleyl-PE. Furthermore, PEPCK-M silencing abrogated cancer growth in a lung cancer cell xenograft model. In conclusion, glycerol phosphate formation for de novo GPL synthesis via glyceroneogenesis is a newly characterized anabolic pathway in cancer cells mediated by PEPCK-M under conditions of severe nutrient deprivation.}, } @article {pmid29844164, year = {2018}, author = {Nair, P}, title = {QnAs with Caroline Dean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5824-5826}, doi = {10.1073/pnas.1807547115}, pmid = {29844164}, issn = {1091-6490}, mesh = {*Botany ; Climate ; Female ; Flowers/physiology ; Humans ; *Molecular Biology ; *Plant Physiological Phenomena ; United Kingdom ; }, } @article {pmid29844163, year = {2018}, author = {Xue, R and Ruhl, DA and Briguglio, JS and Figueroa, AG and Pearce, RA and Chapman, ER}, title = {Doc2-mediated superpriming supports synaptic augmentation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5605-E5613}, pmid = {29844163}, issn = {1091-6490}, support = {R01 GM118801/GM/NIGMS NIH HHS/United States ; R01 MH061876/MH/NIMH NIH HHS/United States ; R35 NS097362/NS/NINDS NIH HHS/United States ; T32 GM007507/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Calcium/metabolism ; Calcium-Binding Proteins/*metabolism ; Cell Line ; HEK293 Cells ; Hippocampus/metabolism ; Humans ; Mice ; Neuronal Plasticity/physiology ; Neurons/metabolism ; Rats ; Synapses/*metabolism ; Synaptic Transmission/physiology ; Synaptic Vesicles/*metabolism ; }, abstract = {Various forms of synaptic plasticity underlie aspects of learning and memory. Synaptic augmentation is a form of short-term plasticity characterized by synaptic enhancement that persists for seconds following specific patterns of stimulation. The mechanisms underlying this form of plasticity are unclear but are thought to involve residual presynaptic Ca2+ Here, we report that augmentation was reduced in cultured mouse hippocampal neurons lacking the Ca2+ sensor, Doc2; other forms of short-term enhancement were unaffected. Doc2 binds Ca2+ and munc13 and translocates to the plasma membrane to drive augmentation. The underlying mechanism was not associated with changes in readily releasable pool size or Ca2+ dynamics, but rather resulted from superpriming a subset of synaptic vesicles. Hence, Doc2 forms part of the Ca2+-sensing apparatus for synaptic augmentation via a mechanism that is molecularly distinct from other forms of short-term plasticity.}, } @article {pmid29844162, year = {2018}, author = {Rao, JS and Zhao, C and Zhang, A and Duan, H and Hao, P and Wei, RH and Shang, J and Zhao, W and Liu, Z and Yu, J and Fan, KS and Tian, Z and He, Q and Song, W and Yang, Z and Sun, YE and Li, X}, title = {NT3-chitosan enables de novo regeneration and functional recovery in monkeys after spinal cord injury.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5595-E5604}, doi = {10.1073/pnas.1804735115}, pmid = {29844162}, issn = {1091-6490}, support = {R21 NS095184/NS/NINDS NIH HHS/United States ; U54 HD087101/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Axons/drug effects ; Chitosan/*pharmacology ; Diffusion Tensor Imaging/methods ; Female ; Haplorhini ; Motor Neurons/drug effects ; Nerve Regeneration/*drug effects ; Neurotrophin 3/*pharmacology ; Pyramidal Tracts/drug effects ; Recovery of Function/*drug effects ; Spinal Cord/drug effects ; Spinal Cord Injuries/*drug therapy ; }, abstract = {Spinal cord injury (SCI) often leads to permanent loss of motor, sensory, and autonomic functions. We have previously shown that neurotrophin3 (NT3)-loaded chitosan biodegradable material allowed for prolonged slow release of NT3 for 14 weeks under physiological conditions. Here we report that NT3-loaded chitosan, when inserted into a 1-cm gap of hemisectioned and excised adult rhesus monkey thoracic spinal cord, elicited robust axonal regeneration. Labeling of cortical motor neurons indicated motor axons in the corticospinal tract not only entered the injury site within the biomaterial but also grew across the 1-cm-long lesion area and into the distal spinal cord. Through a combination of magnetic resonance diffusion tensor imaging, functional MRI, electrophysiology, and kinematics-based quantitative walking behavioral analyses, we demonstrated that NT3-chitosan enabled robust neural regeneration accompanied by motor and sensory functional recovery. Given that monkeys and humans share similar genetics and physiology, our method is likely translatable to human SCI repair.}, } @article {pmid29844161, year = {2018}, author = {Longman, J and Veres, D and Finsinger, W and Ersek, V}, title = {Exceptionally high levels of lead pollution in the Balkans from the Early Bronze Age to the Industrial Revolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5661-E5668}, pmid = {29844161}, issn = {1091-6490}, mesh = {Archaeology/history/statistics & numerical data ; Balkan Peninsula ; Environment ; Environmental Monitoring/*history/*statistics & numerical data ; Environmental Pollution/*history/*statistics & numerical data ; Europe ; History, 16th Century ; History, Ancient ; Lead/*adverse effects/*chemistry ; Metallurgy/history/statistics & numerical data ; Minerals/adverse effects/chemistry ; Mining/history/statistics & numerical data ; Soil/chemistry ; Soil Pollutants/adverse effects/chemistry ; }, abstract = {The Balkans are considered the birthplace of mineral resource exploitation and metalworking in Europe. However, since knowledge of the timing and extent of metallurgy in southeastern Europe is largely constrained by discontinuous archaeological findings, the long-term environmental impact of past mineral resource exploitation is not fully understood. Here, we present a high-resolution and continuous geochemical record from a peat bog in western Serbia, providing a clear indication of the extent and magnitude of environmental pollution in this region, and a context in which to place archaeological findings. We observe initial evidence of anthropogenic lead (Pb) pollution during the earliest part of the Bronze Age [∼3,600 years before Common Era (BCE)], the earliest such evidence documented in European environmental records. A steady, almost linear increase in Pb concentration after 600 BCE, until ∼1,600 CE is observed, documenting the development in both sophistication and extent of southeastern European metallurgical activity throughout Antiquity and the medieval period. This provides an alternative view on the history of mineral exploitation in Europe, with metal-related pollution not ceasing at the fall of the western Roman Empire, as was the case in western Europe. Further comparison with other Pb pollution records indicates the amount of Pb deposited in the Balkans during the medieval period was, if not greater, at least similar to records located close to western European mining regions, suggestive of the key role the Balkans have played in mineral resource exploitation in Europe over the last 5,600 years.}, } @article {pmid29844160, year = {2018}, author = {Lane, KD and Mu, J and Lu, J and Windle, ST and Liu, A and Sun, PD and Wellems, TE}, title = {Selection of Plasmodium falciparum cytochrome B mutants by putative PfNDH2 inhibitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6285-6290}, pmid = {29844160}, issn = {1091-6490}, mesh = {Antimalarials/pharmacology ; Cytochromes b/*genetics ; Drug Resistance/drug effects ; Electron Transport Chain Complex Proteins/genetics ; Malaria, Falciparum/drug therapy/genetics/parasitology ; Molecular Docking Simulation/methods ; Mutation/genetics ; NADH Dehydrogenase/*antagonists & inhibitors ; Plasmodium falciparum/drug effects/*genetics ; Quinolones/pharmacology ; }, abstract = {Malaria control is threatened by a limited pipeline of effective pharmaceuticals against drug-resistant strains of Plasmodium falciparum Components of the mitochondrial electron transport chain (ETC) are attractive targets for drug development, owing to exploitable differences between the parasite and human ETC. Disruption of ETC function interferes with metabolic processes including de novo pyrimidine synthesis, essential for nucleic acid replication. We investigated the effects of ETC inhibitor selection on two distinct P. falciparum clones, Dd2 and 106/1. Compounds CK-2-68 and RYL-552, substituted quinolones reported to block P. falciparum NADH dehydrogenase 2 (PfNDH2; a type II NADH:quinone oxidoreductase), unexpectedly selected mutations at the quinol oxidation (Qo) pocket of P. falciparum cytochrome B (PfCytB). Selection experiments with atovaquone (ATQ) on 106/1 parasites yielded highly resistant PfCytB Y268S mutants seen in clinical infections that fail ATQ-proguanil treatment. In contrast, ATQ pressure on Dd2 yielded moderately resistant parasites carrying a PfCytB M133I or K272R mutation. Strikingly, all ATQ-selected mutants demonstrated little change or slight increase of sensitivity to CK-2-68 or RYL-552. Molecular docking studies demonstrated binding of all three ETC inhibitors to the Qo pocket of PfCytB, where Y268 forms strong van der Waals interactions with the hydroxynaphthoquinone ring of ATQ but not the quinolone ring of CK-2-68 or RYL-552. Our results suggest that combinations of suitable ETC inhibitors may be able to subvert or delay the development of P. falciparum drug resistance.}, } @article {pmid29844159, year = {2018}, author = {Zhang, X and Zhou, W and Chen, Q and Fang, M and Zheng, S and Scheres, B and Li, C}, title = {Mediator subunit MED31 is required for radial patterning of Arabidopsis roots.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5624-E5633}, doi = {10.1073/pnas.1800592115}, pmid = {29844159}, issn = {1091-6490}, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; Gene Expression Regulation, Plant/genetics ; Mediator Complex/*genetics ; Plant Roots/*genetics ; Promoter Regions, Genetic/genetics ; Stem Cells/physiology ; Transcription, Genetic/genetics ; }, abstract = {Stem cell specification in multicellular organisms relies on the precise spatiotemporal control of RNA polymerase II (Pol II)-dependent gene transcription, in which the evolutionarily conserved Mediator coactivator complex plays an essential role. In Arabidopsis thaliana, SHORTROOT (SHR) and SCARECROW (SCR) orchestrate a transcriptional program that determines the fate and asymmetrical divisions of stem cells generating the root ground tissue. The mechanism by which SHR/SCR relays context-specific regulatory signals to the Pol II general transcription machinery is unknown. Here, we report the role of Mediator in controlling the spatiotemporal transcriptional output of SHR/SCR during asymmetrical division of stem cells and ground tissue patterning. The Mediator subunit MED31 interacted with SCR but not SHR. Reduction of MED31 disrupted the spatiotemporal activation of CYCLIND6;1 (CYCD6;1), leading to defective asymmetrical division of stem cells generating ground tissue. MED31 was recruited to the promoter of CYCD6;1 in an SCR-dependent manner. MED31 was involved in the formation of a dynamic MED31/SCR/SHR ternary complex through the interface protein SCR. We demonstrate that the relative protein abundance of MED31 and SHR in different cell types regulates the dynamic formation of the ternary complex, which provides a tunable switch to strictly control the spatiotemporal transcriptional output. This study provides valuable clues to understand the mechanism by which master transcriptional regulators control organ patterning.}, } @article {pmid29844158, year = {2018}, author = {Callender, JA and Yang, Y and Lordén, G and Stephenson, NL and Jones, AC and Brognard, J and Newton, AC}, title = {Protein kinase Cα gain-of-function variant in Alzheimer's disease displays enhanced catalysis by a mechanism that evades down-regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5497-E5505}, pmid = {29844158}, issn = {1091-6490}, support = {R01 GM043154/GM/NIGMS NIH HHS/United States ; R35 GM122523/GM/NIGMS NIH HHS/United States ; R37 GM043154/GM/NIGMS NIH HHS/United States ; T32 GM007752/GM/NIGMS NIH HHS/United States ; //Cancer Research UK/United Kingdom ; }, mesh = {Alzheimer Disease/*genetics/metabolism ; Animals ; Brain/metabolism ; COS Cells ; CRISPR-Cas Systems/genetics ; Calcium/metabolism ; Catalysis ; Catalytic Domain/genetics ; Cell Line ; Cercopithecus aethiops ; Down-Regulation/*genetics ; Enzyme Activation/genetics ; Gain of Function Mutation/*genetics ; Humans ; Mice ; Mice, Inbred C57BL ; Mutation/genetics ; Phosphorylation/genetics ; Protein Kinase C-alpha/*genetics ; Signal Transduction/genetics ; }, abstract = {Conventional protein kinase C (PKC) family members are reversibly activated by binding to the second messengers Ca2+ and diacylglycerol, events that break autoinhibitory constraints to allow the enzyme to adopt an active, but degradation-sensitive, conformation. Perturbing these autoinhibitory constraints, resulting in protein destabilization, is one of many mechanisms by which PKC function is lost in cancer. Here, we address how a gain-of-function germline mutation in PKCα in Alzheimer's disease (AD) enhances signaling without increasing vulnerability to down-regulation. Biochemical analyses of purified protein demonstrate that this mutation results in an ∼30% increase in the catalytic rate of the activated enzyme, with no changes in the concentrations of Ca2+ or lipid required for half-maximal activation. Molecular dynamics simulations reveal that this mutation has both localized and allosteric effects, most notably decreasing the dynamics of the C-helix, a key determinant in the catalytic turnover of kinases. Consistent with this mutation not altering autoinhibitory constraints, live-cell imaging studies reveal that the basal signaling output of PKCα-M489V is unchanged. However, the mutant enzyme in cells displays increased sensitivity to an inhibitor that is ineffective toward scaffolded PKC, suggesting the altered dynamics of the kinase domain may influence protein interactions. Finally, we show that phosphorylation of a key PKC substrate, myristoylated alanine-rich C-kinase substrate, is increased in brains of CRISPR-Cas9 genome-edited mice containing the PKCα-M489V mutation. Our results unveil how an AD-associated mutation in PKCα permits enhanced agonist-dependent signaling via a mechanism that evades the cell's homeostatic down-regulation of constitutively active PKCα.}, } @article {pmid29844157, year = {2018}, author = {Shi, H and Lyu, M and Luo, Y and Liu, S and Li, Y and He, H and Wei, N and Deng, XW and Zhong, S}, title = {Genome-wide regulation of light-controlled seedling morphogenesis by three families of transcription factors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6482-6487}, pmid = {29844157}, issn = {1091-6490}, support = {R01 GM047850/GM/NIGMS NIH HHS/United States ; R37 GM047850/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/genetics ; Arabidopsis Proteins/genetics ; Carrier Proteins/genetics ; Darkness ; Gene Expression Regulation, Plant/*genetics ; Genome-Wide Association Study/methods ; Hypocotyl/genetics ; Light ; Morphogenesis/*genetics ; Mutation/genetics ; Nuclear Proteins/genetics ; Seedlings/*genetics ; Signal Transduction/genetics ; Transcription Factors/*genetics ; Transcriptional Activation/genetics ; }, abstract = {Three families of transcription factors have been reported to play key roles in light control of Arabidopsis seedling morphogenesis. Among them, bHLH protein PIFs and plant-specific protein EIN3/EIN3-LIKE 1 (EIN3/EIL1) accumulate in the dark to maintain skotomorphogenesis. On the other hand, HY5 and HY5 HOMOLOG (HYH), two related bZIP proteins, are stabilized in light and promote photomorphogenic development. To systemically investigate the transcriptional regulation of light-controlled seedling morphogenesis, we generated HY5ox/pifQein3eil1, which contained mutations of EIN3/EIL1 and four PIF genes (pifQein3eil1) and overexpression of HY5 Our results show that dark-grown HY5ox/pifQein3eil1 seedlings display a photomorphogenesis highly similar to that of wild-type seedlings grown in continuous light, with remarkably enhanced photomorphogenic phenotypes compared with the pifQ mutants. Consistent with the genetic evidence, transcriptome analysis indicated that PIFs, EIN3/EIL1, and HY5 are dominant transcription factors in collectively mediating a wide range of light-caused genome-wide transcriptional changes. Moreover, PIFs and EIN3/EIL1 independently control the expression of light-regulated genes such as HLS1 to cooperatively regulate apical hook formation, hypocotyl elongation, and cotyledon opening and expansion. This study illustrates a comprehensive regulatory network of transcription activities that correspond to specific morphological aspects in seedling skotomorphogenesis and photomorphogenesis.}, } @article {pmid29844156, year = {2018}, author = {Marini, A and Rotblat, B and Sbarrato, T and Niklison-Chirou, MV and Knight, JRP and Dudek, K and Jones, C and Bushell, M and Knight, RA and Amelio, I and Willis, AE and Melino, G}, title = {TAp73 contributes to the oxidative stress response by regulating protein synthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6219-6224}, doi = {10.1073/pnas.1718531115}, pmid = {29844156}, issn = {1091-6490}, support = {//Medical Research Council/United Kingdom ; }, mesh = {A549 Cells ; HEK293 Cells ; Humans ; Mitochondria/metabolism ; Oxidative Stress/*genetics ; Protein Biosynthesis/*genetics ; Reactive Oxygen Species/metabolism ; TOR Serine-Threonine Kinases/genetics/metabolism ; Tumor Protein p73/*genetics/*metabolism ; }, abstract = {TAp73 is a transcription factor that plays key roles in brain development, aging, and cancer. At the cellular level, TAp73 is a critical homeostasis-maintaining factor, particularly following oxidative stress. Although major studies focused on TAp73 transcriptional activities have indicated a contribution of TAp73 to cellular metabolism, the mechanisms underlying its role in redox homeostasis have not been completely elucidated. Here we show that TAp73 contributes to the oxidative stress response by participating in the control of protein synthesis. Regulation of mRNA translation occupies a central position in cellular homeostasis during the stress response, often by reducing global rates of protein synthesis and promoting translation of specific mRNAs. TAp73 depletion results in aberrant ribosomal RNA (rRNA) processing and impaired protein synthesis. In particular, polysomal profiles show that TAp73 promotes the integration of mRNAs that encode rRNA-processing factors in polysomes, supporting their translation. Concurrently, TAp73 depletion causes increased sensitivity to oxidative stress that correlates with reduced ATP levels, hyperactivation of AMPK, and translational defects. TAp73 is important for maintaining active translation of mitochondrial transcripts in response to oxidative stress, thus promoting mitochondrial activity. Our results indicate that TAp73 contributes to redox homeostasis by affecting the translational machinery, facilitating the translation of specific mitochondrial transcripts. This study identifies a mechanism by which TAp73 contributes to the oxidative stress response and describes a completely unexpected role for TAp73 in regulating protein synthesis.}, } @article {pmid29844155, year = {2018}, author = {Gabrielsen, P}, title = {QnAs with Joanne Chory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6102-6103}, doi = {10.1073/pnas.1807544115}, pmid = {29844155}, issn = {1091-6490}, mesh = {Arabidopsis/genetics ; *Awards and Prizes ; Female ; *Genes, Plant ; *Genetics ; Humans ; }, } @article {pmid29844116, year = {2018}, author = {Mann, A}, title = {Core Concept: "Twisted" light beams promise an optical revolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5621-5623}, pmid = {29844116}, issn = {1091-6490}, } @article {pmid29844057, year = {2018}, author = {Breaker, RR}, title = {Riboswitches and Translation Control.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a032797}, pmid = {29844057}, issn = {1943-0264}, abstract = {A growing collection of bacterial riboswitch classes is being discovered that sense central metabolites, coenzymes, and signaling molecules. Included among the various mechanisms of gene regulation exploited by these RNA regulatory elements are several that modulate messenger RNA (mRNA) translation. In this review, the mechanisms of riboswitch-mediated translation control are summarized to highlight both their diversity and potential ancient origins. These mechanisms include ligand-gated presentation or occlusion of ribosome-binding sites, control of alternative splicing of mRNAs, and the regulation of mRNA stability. Moreover, speculation on the potential for novel riboswitch discoveries is presented, including a discussion on the potential for the discovery of a greater diversity of mechanisms for translation control.}, } @article {pmid29843923, year = {2018}, author = {Harris, LK and Theriot, JA}, title = {Surface Area to Volume Ratio: A Natural Variable for Bacterial Morphogenesis.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {815-832}, pmid = {29843923}, issn = {1878-4380}, support = {//Howard Hughes Medical Institute/United States ; P50 GM107615/GM/NIGMS NIH HHS/United States ; R01 AI036929/AI/NIAID NIH HHS/United States ; R37 AI036929/AI/NIAID NIH HHS/United States ; }, abstract = {An immediately observable feature of bacteria is that cell size and shape are remarkably constant and characteristic for a given species in a particular condition, but vary quantitatively with physiological parameters such as growth rate, indicating both genetic and environmental regulation. However, despite decades of research, the molecular mechanisms underlying bacterial morphogenesis have remained incompletely characterized. We recently demonstrated that a wide range of bacterial species exhibit a robust surface area to volume ratio (SA/V) homeostasis. Because cell size, shape, and SA/V are mathematically interconnected, if SA/V is indeed the natural variable that cells actively monitor, this finding has critical implications for our understanding of bacterial morphogenesis, placing fundamental constraints on the sizes and shapes that cells can adopt. In this Opinion article we discuss the broad implications that this novel perspective has for the field of bacterial growth and morphogenesis.}, } @article {pmid29843819, year = {2018}, author = {Taheri, RA and Motedayyen, H and Ghotloo, S and Masjedi, M and Mosaffa, N and Mirshafiey, A and Saffari, M}, title = {The effect of lipopolysaccharide on the expression level of immunomodulatory and immunostimulatory factors of human amniotic epithelial cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {343}, pmid = {29843819}, issn = {1756-0500}, support = {345290//This study was financially supported by Kashan University of Medical Sciences (KAUMS)./ ; }, mesh = {Adult ; Amnion/*cytology ; Cytokines/*drug effects ; *Epithelial Cells/drug effects/immunology/metabolism ; Female ; *Fetal Stem Cells/drug effects/immunology/metabolism ; Humans ; Immunologic Factors/*pharmacology ; Lipopolysaccharides/*pharmacology ; Pregnancy ; Prostaglandin-E Synthases/*drug effects ; }, abstract = {OBJECTIVE: Human amniotic epithelial cells (hAECs) are a novel source of stem cells and have immunomodulatory effects on both the innate and adoptive immune system. hAECs can differentiate into multiple cell lineages that make them a suitable cell source for regenerative medicine. These cells express multiple toll-like receptors (TLRs) and respond to various TLR ligands. This study aimed to evaluate the effect of lipopolysaccharide (LPS), a TLR4 ligand, on the level of immunomodulatory and immunostimulatory factors of hAECs.

RESULTS: Our results indicated that LPS had the ability to up-regulate the expression of prostaglandin E2 synthase and transforming growth factor-beta1 in hAECs. However, there was no change in the level of interleukin-1beta, interleukin-6 and interleukin-10 in hAECs when were stimulated with LPS. In addition, we observed tumor necrosis factor-alpha was only expressed at very low level in some of hAECs samples which its expression was independent of the effects of LPS.}, } @article {pmid29843816, year = {2018}, author = {Nakai, Y and Tanaka, N and Miyake, M and Inoue, T and Anai, S and Fujimoto, K}, title = {Response to flutamide, as second-line therapy after bicalutamide, predicts efficacy of abiraterone, not that of enzalutamide.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {342}, pmid = {29843816}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Androstenes/administration & dosage/*pharmacology ; Anilides/administration & dosage/*pharmacology ; Antineoplastic Agents/administration & dosage/*pharmacology ; Disease-Free Survival ; Flutamide/administration & dosage/*pharmacology ; Humans ; Male ; Middle Aged ; Nitriles/administration & dosage/*pharmacology ; *Outcome Assessment (Health Care) ; Phenylthiohydantoin/administration & dosage/*analogs & derivatives/pharmacology ; Prostate-Specific Antigen ; Prostatic Neoplasms, Castration-Resistant/*drug therapy ; Retrospective Studies ; Tosyl Compounds/administration & dosage/*pharmacology ; }, abstract = {OBJECTIVE: The objective of this retrospective study was to evaluate whether the effect of second-line therapy of flutamide after bicalutamide can predict the response to abiraterone.

RESULTS: Thirty-four patients received abiraterone and 32 received enzalutamide after treatment with second-line flutamide for castration-resistant prostate cancer. Prostate-specific antigen-progression-free survival during treatment with abiraterone or enzalutamide was the endpoint. The response to flutamide therapy was defined as any decrease in prostate-specific antigen compared to baseline prostate-specific antigen. Among the abiraterone-treated patients, those for whom flutamide after bicalutamide was effective showed significantly lower prostate-specific antigen changes than those for whom it was ineffective (P = 0.0175). Prostate-specific antigen-progression-free survival was significantly higher in the abiraterone patients when flutamide was effective than in the patients when it was ineffective (P = 0.027). However, in enzalutamide-treated patients, the prostate-specific antigen changes were not significantly different between those for whom flutamide after bicalutamide was effective and those for whom it was ineffective (P = 0.75). In the enzalutamide patients, prostate-specific antigen-progression-free survival was not significantly different between those for whom flutamide was effective and those for whom it was ineffective (P = 0.92). Therefore, the response to second-line flutamide predicts the efficacy of abiraterone. This information should be helpful when choosing between abiraterone and enzalutamide for patients with castration-resistant prostate cancer.}, } @article {pmid29843815, year = {2018}, author = {Weerasinghe, NP and Vidanagama, D and Perera, B and Herath, HMM and De Silva Nagahawatte, A}, title = {Re-exploring the value of surveillance cultures in predicting pathogens of late onset neonatal sepsis in a tertiary care hospital in southern Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {340}, pmid = {29843815}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*therapeutic use ; Bacteriological Techniques/*standards ; Cohort Studies ; Cross Infection/*diagnosis/microbiology ; *Enterobacteriaceae/drug effects/isolation & purification/pathogenicity ; Female ; Humans ; Infant, Newborn ; Intensive Care Units, Neonatal/*statistics & numerical data ; Male ; Microbial Sensitivity Tests ; Neonatal Sepsis/*diagnosis/microbiology ; Predictive Value of Tests ; Sensitivity and Specificity ; Sri Lanka ; Tertiary Care Centers ; }, abstract = {OBJECTIVE: To identify the validity of surveillance cultures in predicting causative organism(s) of late onset neonatal sepsis.

RESULTS: Prospective analytical study was conducted from January to April 2011 at the Neonatal Intensive Care Unit, Teaching Hospital, Karapitiya, Galle, Sri Lanka. Fifty neonates were screened on admission and weekly thereafter for colonization with potential pathogens. On suspicion of infection, relevant samples were cultured and tested for antibiotic sensitivity. There were 55 episodes of clinically suspected infections including 33 nosocomial infections. One-third (17/55) of all clinically suspected infections were culture positive. Out of 55, only 33 episodes were clinically suspected nosocomial infections. Clinically suspected nosocomial infection rate was 50/1000 patient-days. Culture proven nosocomial infection rate was 13.61/1000 patient-days. Coliforms were the commonest clinical isolate (76%) and 2/3 of them produced extended spectrum β lactamase. More than 80% of the isolates causing late onset sepsis were sensitive to carbapenems and aminoglycosides. Sensitivity, specificity, positive predictive value and negative predictive value of surveillance cultures were 77.8, 37.5, 31.8 and 81.8%, respectively. Surveillance samples can be used to predict pathogens of late-onset sepsis. Broad-spectrum antibiotics (carbapenems, aminoglycosides) are recommended as empirical therapy for late-onset neonatal sepsis.}, } @article {pmid29843806, year = {2018}, author = {De Meulder, B and Lefaudeux, D and Bansal, AT and Mazein, A and Chaiboonchoe, A and Ahmed, H and Balaur, I and Saqi, M and Pellet, J and Ballereau, S and Lemonnier, N and Sun, K and Pandis, I and Yang, X and Batuwitage, M and Kretsos, K and van Eyll, J and Bedding, A and Davison, T and Dodson, P and Larminie, C and Postle, A and Corfield, J and Djukanovic, R and Chung, KF and Adcock, IM and Guo, YK and Sterk, PJ and Manta, A and Rowe, A and Baribaud, F and Auffray, C and , }, title = {A computational framework for complex disease stratification from multiple large-scale datasets.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {60}, pmid = {29843806}, issn = {1752-0509}, support = {U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; U-BIOPRED IMI n°115010//Innovative Medicines Initiative/ ; eTRIKS IMI n°115446//Innovative Medicines Initiative/ ; }, abstract = {BACKGROUND: Multilevel data integration is becoming a major area of research in systems biology. Within this area, multi-'omics datasets on complex diseases are becoming more readily available and there is a need to set standards and good practices for integrated analysis of biological, clinical and environmental data. We present a framework to plan and generate single and multi-'omics signatures of disease states.

METHODS: The framework is divided into four major steps: dataset subsetting, feature filtering, 'omics-based clustering and biomarker identification.

RESULTS: We illustrate the usefulness of this framework by identifying potential patient clusters based on integrated multi-'omics signatures in a publicly available ovarian cystadenocarcinoma dataset. The analysis generated a higher number of stable and clinically relevant clusters than previously reported, and enabled the generation of predictive models of patient outcomes.

CONCLUSIONS: This framework will help health researchers plan and perform multi-'omics big data analyses to generate hypotheses and make sense of their rich, diverse and ever growing datasets, to enable implementation of translational P4 medicine.}, } @article {pmid29843780, year = {2018}, author = {Dalinjong, PA and Wang, AY and Homer, CSE}, title = {The implementation of the free maternal health policy in rural Northern Ghana: synthesised results and lessons learnt.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {341}, pmid = {29843780}, issn = {1756-0500}, mesh = {Cross-Sectional Studies ; Ghana ; *Health Policy/economics ; *Health Services Accessibility/economics/standards/statistics & numerical data ; Humans ; *Maternal Health Services/economics/standards/statistics & numerical data ; *National Health Programs/economics/standards/statistics & numerical data ; *Patient Acceptance of Health Care/statistics & numerical data ; Qualitative Research ; *Quality of Health Care/economics/standards/statistics & numerical data ; }, abstract = {OBJECTIVE: A free maternal health policy was implemented under Ghana's National Health Insurance Scheme to promote the use of maternal health services. Under the policy, women are entitled to free services throughout pregnancy and at childbirth. A mixed methods study involving women, providers and insurance managers was carried out in the Kassena-Nankana municipality of Ghana. It explored the affordability, availability, acceptability and quality of services. In this manuscript, we present synthesised results categorised as facilitators and barriers to access as well as lessons learnt (implications).

RESULTS: Reasonable waiting times, cleanliness of facilities as well as good interpersonal relationships with providers were the facilitators to access. Barriers included out of pocket payments, lack of, or inadequate supply of drugs and commodities, equipment, water, electricity and emergency transport. Four lessons (implications) were identified. Firstly, out of pocket payments persisted. Secondly, the health system was not strengthened before implementing the free maternal health policy. Thirdly, lower level facilities were poorly resourced. Finally, the lack of essential inputs and infrastructure affected quality of care and therefore, access to care. It is suggested that the Government of Ghana, the Health Insurance Scheme and other stakeholders improve the provision of resources to facilities.}, } @article {pmid29843773, year = {2018}, author = {Isha, IT and Alam, ZHMN and Shaha, BK and Bari, MS and Bari, MZJ and Chowdhury, FR}, title = {Paraquat induced acute kidney injury and lung fibrosis: a case report from Bangladesh.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {344}, pmid = {29843773}, issn = {1756-0500}, mesh = {Acute Kidney Injury/*chemically induced ; Adolescent ; Bangladesh ; Herbicides/*poisoning ; Humans ; Male ; Paraquat/*poisoning ; Pulmonary Fibrosis/*chemically induced ; }, abstract = {BACKGROUND: Since Bangladesh government issued a ban on the use of highly toxic WHO Class I pesticides, annual consumption of herbicides like Paraquat have been sharply increasing in the markets. Paraquat poisoning is an emerging public health threat and its high mortality rate is responsible for a significant number of deaths. Diagnostic limitations and unavailable sample at presentation have resulted in under-reporting and lack of awareness among the treating physicians, making Paraquat poisoning one of the most neglected toxicological emergencies. Herein, we present a case of Paraquat induced multi-organ failure and emphasis on pitfalls in the management.

CASE PRESENTATION: An 18-years-old healthy male was admitted in Sylhet M.A.G Osmani Medical College Hospital with history of attempted suicide by Paraquat ingestion. On admission, he had high serum creatinine but otherwise asymptomatic. He was discharged on day 10 when his renal functions returned to normal. But On day 15, he started having respiratory symptoms-unresponsive to any of the local treatments he received, and by day 30, he developed overt lung fibrosis. We present sequential blood picture, radiographs and CT scans demonstrating Paraquat induced kidney and lung injury over the course of 30 days.

CONCLUSION: Paraquat poisoning can lead to death and fatal long-term consequences. All cases of Paraquat poisoning, regardless of symptoms, must be hospitalized and observed for early detection of complications. Distribution of Paraquat should be restricted and/or banned as 38 other countries have done so, which we believe will greatly reduce poisoning related mortality.}, } @article {pmid29843739, year = {2018}, author = {Pereira, B and Miguel, J and Vilaça, P and Soares, S and Rocha, I and Carneiro, S}, title = {Reconstruction of a genome-scale metabolic model for Actinobacillus succinogenes 130Z.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {61}, pmid = {29843739}, issn = {1752-0509}, support = {UID/BIO/04469/2013//Fundação para a Ciência e a Tecnologia/ ; KBBE-2012-6-311935//FP7 International Cooperation/ ; 23060//European Regional Development Fund ()/ ; }, abstract = {BACKGROUND: Actinobacillus succinogenes is a promising bacterial catalyst for the bioproduction of succinic acid from low-cost raw materials. In this work, a genome-scale metabolic model was reconstructed and used to assess the metabolic capabilities of this microorganism under producing conditions.

RESULTS: The model, iBP722, was reconstructed based on the functional reannotation of the complete genome sequence of A. succinogenes 130Z and manual inspection of metabolic pathways, covering 1072 enzymatic reactions associated with 722 metabolic genes that involve 713 metabolites. The highly curated model was effective in capturing the growth of A. succinogenes on various carbon sources, as well as the SA production under various growth conditions with fair agreement between experimental and predicted data. Calculated flux distributions under different conditions show that a number of metabolic pathways are affected by the activity of some metabolic enzymes at key nodes in metabolism, including the transport mechanism of carbon sources and the ability to fix carbon dioxide.

CONCLUSIONS: The established genome-scale metabolic model can be used for model-driven strain design and medium alteration to improve succinic acid yields.}, } @article {pmid29843722, year = {2018}, author = {Migliori, B and Datta, MS and Dupre, C and Apak, MC and Asano, S and Gao, R and Boyden, ES and Hermanson, O and Yuste, R and Tomer, R}, title = {Light sheet theta microscopy for rapid high-resolution imaging of large biological samples.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {57}, pmid = {29843722}, issn = {1741-7007}, support = {R01 MH101218/MH/NIMH NIH HHS/United States ; DP1 EY024503/EY/NEI NIH HHS/United States ; }, abstract = {BACKGROUND: Advances in tissue clearing and molecular labeling methods are enabling unprecedented optical access to large intact biological systems. These developments fuel the need for high-speed microscopy approaches to image large samples quantitatively and at high resolution. While light sheet microscopy (LSM), with its high planar imaging speed and low photo-bleaching, can be effective, scaling up to larger imaging volumes has been hindered by the use of orthogonal light sheet illumination.

RESULTS: To address this fundamental limitation, we have developed light sheet theta microscopy (LSTM), which uniformly illuminates samples from the same side as the detection objective, thereby eliminating limits on lateral dimensions without sacrificing the imaging resolution, depth, and speed. We present a detailed characterization of LSTM, and demonstrate its complementary advantages over LSM for rapid high-resolution quantitative imaging of large intact samples with high uniform quality.

CONCLUSIONS: The reported LSTM approach is a significant step for the rapid high-resolution quantitative mapping of the structure and function of very large biological systems, such as a clarified thick coronal slab of human brain and uniformly expanded tissues, and also for rapid volumetric calcium imaging of highly motile animals, such as Hydra, undergoing non-isomorphic body shape changes.}, } @article {pmid29843714, year = {2018}, author = {Bapteste, E and Huneman, P}, title = {Towards a Dynamic Interaction Network of Life to unify and expand the evolutionary theory.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {56}, pmid = {29843714}, issn = {1741-7007}, abstract = {The classic Darwinian theory and the Synthetic evolutionary theory and their linear models, while invaluable to study the origins and evolution of species, are not primarily designed to model the evolution of organisations, typically that of ecosystems, nor that of processes. How could evolutionary theory better explain the evolution of biological complexity and diversity? Inclusive network-based analyses of dynamic systems could retrace interactions between (related or unrelated) components. This theoretical shift from a Tree of Life to a Dynamic Interaction Network of Life, which is supported by diverse molecular, cellular, microbiological, organismal, ecological and evolutionary studies, would further unify evolutionary biology.}, } @article {pmid29843697, year = {2018}, author = {Liu, D and Dai, P and Li, S and Ahmed, SS and Shang, Z and Shi, X}, title = {Life-history responses of insects to water-deficit stress: a case study with the aphid Sitobion avenae.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {17}, pmid = {29843697}, issn = {1472-6785}, support = {31572002//National Natural Science Foundation of China/International ; }, abstract = {BACKGROUND: Drought may become one of the greatest challenges for cereal production under future warming scenarios, and its impact on insect pest outbreaks is still controversial. To address this issue, life-history responses of the English grain aphid, Sitobion avenae (Fabricius), from three areas of different drought levels were compared under three water treatments.

RESULTS: Significant differences were identified in developmental time, fecundity and adult weight among S. avenae clones from moist, semiarid and arid areas under all the three water treatments. Semiarid and arid area clones tended to have higher heritability for test life-history traits than moist area clones. We identified significant selection of water-deficit on the developmental time of 1st instar nymphs and adult weight for both semiarid and arid area clones. The impact of intermediate and severe water-stress on S. avenae's fitness was neutral and negative (e.g., decreased fecundity and weight), respectively. Compared with arid-area clones, moist- and semiarid-area clones showed higher extents of adaptation to the water-deficit level of their respective source environment. Adult weight was identified as a good indicator for S. avenae's adaptation potential under different water-stress conditions. After their exposure to intermediate water-deficit stress for only five generations, adult weight and fecundity tended to decrease for moist- and semiarid-area clones, but increase for arid-area clones.

CONCLUSIONS: It is evident from our study that S. avenae clones from moist, semiarid and arid areas have diverged under different water-deficit stress, and such divergence could have a genetic basis. The impact of drought on S. avenae's fitness showed a water-level dependent pattern. Clones of S. avenae were more likely to become adapted to intermediate water-deficit stress than severe water-deficit stress. After continuous water-deficit stress of only five generations, the adaptation potential of S. avenae tended to decrease for moist and semiarid area clones, but increase for arid area clones. The rapid shift of aphids' life-history traits and adaptation potential under drought could have significant implications for their evolutionary dynamics and outbreak risks in future climate change scenarios.}, } @article {pmid29843617, year = {2018}, author = {Caetano-Anolles, K and Kim, K and Kwak, W and Sung, S and Kim, H and Choi, BH and Lim, D}, title = {Genome sequencing and protein domain annotations of Korean Hanwoo cattle identify Hanwoo-specific immunity-related and other novel genes.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {37}, pmid = {29843617}, issn = {1471-2156}, support = {PJ01251902//National Institute of Animal Science, Rural Development Administration (RDA), Republic of Korea/ ; }, abstract = {BACKGROUND: Identification of genetic mechanisms and idiosyncrasies at the breed-level can provide valuable information for potential use in evolutionary studies, medical applications, and breeding of selective traits. Here, we analyzed genomic data collected from 136 Korean Native cattle, known as Hanwoo, using advanced statistical methods.

RESULTS: Results revealed Hanwoo-specific protein domains which were largely characterized by immunoglobulin function. Furthermore, domain interactions of novel Hanwoo-specific genes reveal additional links to immunity. Novel Hanwoo-specific genes linked to muscle and other functions were identified, including protein domains with functions related to energy, fat storage, and muscle function that may provide insight into the mechanisms behind Hanwoo cattle's uniquely high percentage of intramuscular fat and fat marbling.

CONCLUSION: The identification of Hanwoo-specific genes linked to immunity are potentially useful for future medical research and selective breeding. The significant genomic variations identified here can crucially identify genetic novelties that are arising from useful adaptations. These results will allow future researchers to compare and classify breeds, identify important genetic markers, and develop breeding strategies to further improve significant traits.}, } @article {pmid29843615, year = {2018}, author = {Eserman, LA and Jarret, RL and Leebens-Mack, JH}, title = {Parallel evolution of storage roots in morning glories (Convolvulaceae).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {95}, pmid = {29843615}, issn = {1471-2229}, mesh = {Biosynthetic Pathways ; *Evolution, Molecular ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Ipomoea/anatomy & histology/*genetics/metabolism ; Ipomoea batatas/anatomy & histology/genetics/metabolism ; Phenotype ; Plant Roots/anatomy & histology/genetics/metabolism ; RNA, Messenger/genetics ; Starch/biosynthesis ; *Transcriptome ; Up-Regulation ; }, abstract = {BACKGROUND: Storage roots are an ecologically and agriculturally important plant trait that have evolved numerous times in angiosperms. Storage roots primarily function to store carbohydrates underground as reserves for perennial species. In morning glories, storage roots are well characterized in the crop species sweetpotato, where starch accumulates in storage roots. This starch-storage tissue proliferates, and roots thicken to accommodate the additional tissue. In morning glories, storage roots have evolved numerous times. The primary goal of this study is to understand whether this was through parallel evolution, where species use a common genetic mechanism to achieve storage root formation, or through convergent evolution, where storage roots in distantly related species are formed using a different set of genes. Pairs of species where one forms storage roots and the other does not were sampled from two tribes in the morning glory family, the Ipomoeeae and Merremieae. Root anatomy in storage roots and fine roots was examined. Furthermore, we sequenced total mRNA from storage roots and fine roots in these species and analyzed differential gene expression.

RESULTS: Anatomical results reveal that storage roots of species in the Ipomoeeae tribe, such as sweetpotato, accumulate starch similar to species in the Merremieae tribe but differ in vascular tissue organization. In both storage root forming species, more genes were found to be upregulated in storage roots compared to fine roots. Further, we find that fifty-seven orthologous genes were differentially expressed between storage roots and fine roots in both storage root forming species. These genes are primarily involved in starch biosynthesis, regulation of starch biosynthesis, and transcription factor activity.

CONCLUSIONS: Taken together, these results demonstrate that storage roots of species from both morning glory tribes are anatomically different but utilize a common core set of genes in storage root formation. This is consistent with a pattern of parallel evolution, thus highlighting the importance of examining anatomy together with gene expression to understand the evolutionary origins of ecologically and economically important plant traits.}, } @article {pmid29843613, year = {2018}, author = {Gustafsson, C and Willforss, J and Lopes-Pinto, F and Ortiz, R and Geleta, M}, title = {Identification of genes regulating traits targeted for domestication of field cress (Lepidium campestre) as a biennial and perennial oilseed crop.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {36}, pmid = {29843613}, issn = {1471-2156}, abstract = {BACKGROUND: The changing climate and the desire to use renewable oil sources necessitate the development of new oilseed crops. Field cress (Lepidium campestre) is a species in the Brassicaceae family that has been targeted for domestication not only as an oilseed crop that produces seeds with a desirable industrial oil quality but also as a cover/catch crop that provides valuable ecosystem services. Lepidium is closely related to Arabidopsis and display significant proportions of syntenic regions in their genomes. Arabidopsis genes are among the most characterized genes in the plant kingdom and, hence, comparative genomics of Lepidium-Arabidopsis would facilitate the identification of Lepidium candidate genes regulating various desirable traits.

RESULTS: Homologues of 30 genes known to regulate vernalization, flowering time, pod shattering, oil content and quality in Arabidopsis were identified and partially characterized in Lepidium. Alignments of sequences representing field cress and two of its closely related perennial relatives: L. heterophyllum and L. hirtum revealed 243 polymorphic sites across the partial sequences of the 30 genes, of which 95 were within the predicted coding regions and 40 led to a change in amino acids of the target proteins. Within field cress, 34 polymorphic sites including nine non-synonymous substitutions were identified. The phylogenetic analysis of the data revealed that field cress is more closely related to L. heterophyllum than to L. hirtum.

CONCLUSIONS: There is significant variation within and among Lepidium species within partial sequences of the 30 genes known to regulate traits targeted in the present study. The variation within these genes are potentially useful to speed-up the process of domesticating field cress as future oil crop. The phylogenetic relationship between the Lepidium species revealed in this study does not only shed some light on Lepidium genome evolution but also provides important information to develop efficient schemes for interspecific hybridization between different Lepidium species as part of the domestication efforts.}, } @article {pmid29843612, year = {2018}, author = {Hartmann, T and Bernt, M and Middendorf, M}, title = {EqualTDRL: illustrating equivalent tandem duplication random loss rearrangements.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {192}, pmid = {29843612}, issn = {1471-2105}, abstract = {BACKGROUND: To study the differences between two unichromosomal circular genomes, e.g., mitochondrial genomes, under the tandem duplication random loss (TDRL) rearrangement it is important to consider the whole set of potential TDRL rearrangement events that could have taken place. The reason is that for two given circular gene orders there can exist different TDRL rearrangements that transform one of the gene orders into the other. Hence, a TDRL event cannot always be reconstructed only from the knowledge of the circular gene order before a TDRL event and the circular gene order after it.

RESULTS: We present the program EqualTDRL that computes and illustrates the complete set of TDRLs for pairs of circular gene orders that differ by only one TDRL. EqualTDRL considers the circularity of the given genomes and certain restrictions on the TDRL rearrangements. Examples for the latter are sequences of genes that have to be conserved during a TDRL or pairs of genes that frame intergenic regions which might represent remnants of duplicated genes. Additionally, EqualTDRL allows to determine the set of TDRLs that are minimum with respect to the number of duplicated genes.

CONCLUSION: EqualTDRL supports scientists to study the complete set of TDRLs that possibly could have taken place in the evolution of mitochondrial genomes. EqualTDRL is implemented in C++ using the ggplot2 package of the open source programming language R and is freely available from http://pacosy.informatik.uni-leipzig.de/equaltdrl .}, } @article {pmid29843611, year = {2018}, author = {Jiang, M and Chu, Z}, title = {Comparative analysis of plant MKK gene family reveals novel expansion mechanism of the members and sheds new light on functional conservation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {407}, pmid = {29843611}, issn = {1471-2164}, mesh = {Amino Acid Sequence ; Conserved Sequence ; *Evolution, Molecular ; Genomics ; Mitogen-Activated Protein Kinase Kinases/chemistry/*genetics/*metabolism ; Phylogeny ; Plants/*enzymology/*genetics ; Protein Domains ; }, abstract = {BACKGROUND: Mitogen-activated protein kinase (MAPK) cascades play critical functions in almost every aspect of plant growth and development, which regulates many physiological and biochemical processes. As a middle nodal point of the MAPK cascades, although evolutionary analysis of MKK from individual plant families had some reports, their evolutionary history in entire plants is still not clear.

RESULTS: To better understand the evolution and function of plant MKKs, we performed systematical molecular evolutionary analysis of the MAPKK gene family and also surveyed their gene organizations, sequence features and expression patterns in different subfamilies. Phylogenetic analysis showed that plant MAPKK fall into five different groups (Group A-E). Majority orthology groups seemed to be a single or low-copy genes in all plant species analyzed in Group B, C and D, whereas group A MKKs undergo several duplication events, generating multiple gene copies. Further analysis showed that these duplication events were on account of whole genome duplications (WGDs) in plants and the duplicate genes maybe have undergone functional divergence. We also found that group E MKKs had mutation with one change of serine or theronine might lead to inactivity originated through the ancient tandem duplicates in monocots. Moreover, we also identified MKK3 integrated NTF2 domain that might have gradually lost the cytoplasmic-nuclear trafficking activity, which suggests that they may involve with the gene function more and more sophistication in the evolutionary process. Moreover, expression analyses indicated that plant MKK genes play probable roles in UV-B signaling.

CONCLUSION: In general, ancient gene and genome duplications are significantly conducive to the expansion of the plant MKK gene family. Our study reveals two distinct evolutionary patterns for plant MKK proteins and sheds new light on the functional evolution of this gene family.}, } @article {pmid29843609, year = {2018}, author = {Perrier, JP and Sellem, E and Prézelin, A and Gasselin, M and Jouneau, L and Piumi, F and Al Adhami, H and Weber, M and Fritz, S and Boichard, D and Le Danvic, C and Schibler, L and Jammes, H and Kiefer, H}, title = {A multi-scale analysis of bull sperm methylome revealed both species peculiarities and conserved tissue-specific features.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {404}, pmid = {29843609}, issn = {1471-2164}, support = {ANR-13-LAB3-0008-01//Agence Nationale de la Recherche/ ; ANR-11-INBS -0003//Agence Nationale de la Recherche/ ; }, mesh = {Animals ; Cattle ; *DNA Methylation ; *Genomics ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mice ; Organ Specificity ; Species Specificity ; Spermatozoa/*metabolism ; }, abstract = {BACKGROUND: Spermatozoa have a remarkable epigenome in line with their degree of specialization, their unique nature and different requirements for successful fertilization. Accordingly, perturbations in the establishment of DNA methylation patterns during male germ cell differentiation have been associated with infertility in several species. While bull semen is widely used in artificial insemination, the literature describing DNA methylation in bull spermatozoa is still scarce. The purpose of this study was therefore to characterize the bull sperm methylome relative to both bovine somatic cells and the sperm of other mammals through a multiscale analysis.

RESULTS: The quantification of DNA methylation at CCGG sites using luminometric methylation assay (LUMA) highlighted the undermethylation of bull sperm compared to the sperm of rams, stallions, mice, goats and men. Total blood cells displayed a similarly high level of methylation in bulls and rams, suggesting that undermethylation of the bovine genome was specific to sperm. Annotation of CCGG sites in different species revealed no striking bias in the distribution of genome features targeted by LUMA that could explain undermethylation of bull sperm. To map DNA methylation at a genome-wide scale, bull sperm was compared with bovine liver, fibroblasts and monocytes using reduced representation bisulfite sequencing (RRBS) and immunoprecipitation of methylated DNA followed by microarray hybridization (MeDIP-chip). These two methods exhibited differences in terms of genome coverage, and consistently, two independent sets of sequences differentially methylated in sperm and somatic cells were identified for RRBS and MeDIP-chip. Remarkably, in the two sets most of the differentially methylated sequences were hypomethylated in sperm. In agreement with previous studies in other species, the sequences that were specifically hypomethylated in bull sperm targeted processes relevant to the germline differentiation program (piRNA metabolism, meiosis, spermatogenesis) and sperm functions (cell adhesion, fertilization), as well as satellites and rDNA repeats.

CONCLUSIONS: These results highlight the undermethylation of bull spermatozoa when compared with both bovine somatic cells and the sperm of other mammals, and raise questions regarding the dynamics of DNA methylation in bovine male germline. Whether sperm undermethylation has potential interactions with structural variation in the cattle genome may deserve further attention.}, } @article {pmid29843608, year = {2018}, author = {Sedlar, K and Koscova, P and Vasylkivska, M and Branska, B and Kolek, J and Kupkova, K and Patakova, P and Provaznik, I}, title = {Transcription profiling of butanol producer Clostridium beijerinckii NRRL B-598 using RNA-Seq.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {415}, pmid = {29843608}, issn = {1471-2164}, support = {17-00551S//Grantová Agentura České Republiky/ ; }, mesh = {Bacteriophages/genetics ; Butanols/*metabolism ; Clostridium beijerinckii/*genetics/*metabolism/virology ; DNA, Viral/genetics ; Fermentation ; *Gene Expression Profiling ; Kinetics ; Pseudogenes/genetics ; *Sequence Analysis, RNA ; Transcription, Genetic ; }, abstract = {BACKGROUND: Thinning supplies of natural resources increase attention to sustainable microbial production of bio-based fuels. The strain Clostridium beijerinckii NRRL B-598 is a relatively well-described butanol producer regarding its genotype and phenotype under various conditions. However, a link between these two levels, lying in the description of the gene regulation mechanisms, is missing for this strain, due to the lack of transcriptomic data.

RESULTS: In this paper, we present a transcription profile of the strain over the whole fermentation using an RNA-Seq dataset covering six time-points with the current highest dynamic range among solventogenic clostridia. We investigated the accuracy of the genome sequence and particular genome elements, including pseudogenes and prophages. While some pseudogenes were highly expressed, all three identified prophages remained silent. Furthermore, we identified major changes in the transcriptional activity of genes using differential expression analysis between adjacent time-points. We identified functional groups of these significantly regulated genes and together with fermentation and cultivation kinetics captured using liquid chromatography and flow cytometry, we identified basic changes in the metabolism of the strain during fermentation. Interestingly, C. beijerinckii NRRL B-598 demonstrated different behavior in comparison with the closely related strain C. beijerinckii NCIMB 8052 in the latter phases of cultivation.

CONCLUSIONS: We provided a complex analysis of the C. beijerinckii NRRL B-598 fermentation profile using several technologies, including RNA-Seq. We described the changes in the global metabolism of the strain and confirmed the uniqueness of its behavior. The whole experiment demonstrated a good reproducibility. Therefore, we will be able to repeat the experiment under selected conditions in order to investigate particular metabolic changes and signaling pathways suitable for following targeted engineering.}, } @article {pmid29843606, year = {2018}, author = {Mielczarek, M and Frąszczak, M and Nicolazzi, E and Williams, JL and Szyda, J}, title = {Landscape of copy number variations in Bos taurus: individual - and inter-breed variability.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {410}, pmid = {29843606}, issn = {1471-2164}, mesh = {Animals ; Cattle/*genetics ; DNA Copy Number Variations/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: The number of studies of Copy Number Variation in cattle has increased in recent years. This has been prompted by the increased availability of data on polymorphisms and their relationship with phenotypes. In addition, livestock species are good models for some human phenotypes. In the present study, we described the landscape of CNV driven genetic variation in a large population of 146 individuals representing 13 cattle breeds, using whole genome DNA sequence.

RESULTS: A highly significant variation among all individuals and within each breed was observed in the number of duplications (P < 10-15) and in the number of deletions (P < 10-15). We also observed significant differences between breeds for duplication (P = 0.01932) and deletion (P = 0.01006) counts. The same variation CNV length - inter-individual and inter-breed differences were significant for duplications (P < 10-15) and deletions (P < 10-15). Moreover, breed-specific variants were identified, with the largest proportion of breed-specific duplications (9.57%) found for Fleckvieh and breed-specific deletions found for Brown Swiss (5.00%). Such breed-specific CNVs were predominantly located in intragenic regions, however in Simmental, one deletion present in five individuals was found in the coding sequence of a novel gene ENSBTAG00000000688 on chromosome 18. In Brown Swiss, Norwegian Red and Simmental breed-specific deletions were located within KIT and MC1R genes, which are responsible for a coat colour. The functional annotation of coding regions underlying the breed-specific CNVs showed that in Norwegian Red, Guernsey, and Simmental significantly under- and overrepresented GO terms were related to chemical stimulus involved in sensory perception of smell and the KEGG pathways for olfactory transduction. In addition, specifically for the Norwegian Red breed, the dopaminergic synapse KEGG pathway was significantly enriched within deleted parts of the genome.

CONCLUSIONS: The CNV landscape in Bos taurus genome revealed by this study was highly complex, with inter-breed differences, but also a significant variation within breeds. The former, may explain some of the phenotypic differences among analysed breeds, and the latter contributes to within-breed variation available for selection.}, } @article {pmid29843605, year = {2018}, author = {Shu, B and Jia, J and Zhang, J and Sethuraman, V and Yi, X and Zhong, G}, title = {DnaJ homolog subfamily A member1 (DnaJ1) is a newly discovered anti-apoptotic protein regulated by azadirachtin in Sf9 cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {413}, pmid = {29843605}, issn = {1471-2164}, mesh = {Animals ; Apoptosis/*drug effects ; Caspase 3/metabolism ; Cell Nucleus/drug effects/metabolism ; Cell Proliferation/drug effects ; Cell Survival/drug effects ; Gene Knockdown Techniques ; HSP40 Heat-Shock Proteins/deficiency/genetics/*metabolism ; Insect Proteins/*metabolism ; Limonins/*pharmacology ; RNA, Messenger/genetics ; Sf9 Cells ; Spodoptera ; }, abstract = {BACKGROUND: Azadirachtin, one of the most promising botanical insecticides, has been widely used for pest control. Azadirachtin induces apoptosis in insect cell lines, including Sf9, SL-1 and BTI-Tn-5B1-4. Mitochondrial and lysosomal pathways are likely involved in the azadirachtin-induced apoptosis, however, detailed molecular mechanisms remain largely undefined.

RESULTS: Azadirachtin-induced apoptosis in Sf9 cells was verified by morphological observation, Hoechst 33258 staining, and a Caspase-3-based analysis. Comparative two-dimensional gel electrophoresis (2-DE) coupled with a linear ion trap quadrupole (LTQ)-MS/MS analysis identified 12 prominent, differentially expressed proteins following azadirachtin treatment. These differentially expressed genes are involved in regulating cytoskeleton development, signal transduction, gene transcription, and cellular metabolism. Knockdown gene expression of a gene encoding a DnaJ homolog enhanced apoptosis induced by azadirachtin in Sf9 cells.

CONCLUSION: Azadirachtin treatment induces apoptosis in Sf9 cells and affects expression of multiple genes with functions in cytoskeleton development, signal transduction, gene regulation, and cellular metabolisms. Azadirachtin induces apoptosis at least partially by down-regulation of Sf-DnaJ in Sf9 cells.}, } @article {pmid29843604, year = {2018}, author = {Sun, W and Duan, T and Ye, P and Chen, K and Zhang, G and Lai, M and Zhang, H}, title = {TSVdb: a web-tool for TCGA splicing variants analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {405}, pmid = {29843604}, issn = {1471-2164}, support = {81672730//National Natural Science Foundation of China/ ; 81572716//National Natural Science Foundation of China (CN)/ ; B13026//111 Project/ ; 172210271//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Colonic Neoplasms/genetics ; Genomics/*methods ; *Internet ; Neoplasms/*genetics ; *RNA Splicing ; }, abstract = {BACKGROUND: Collaborative projects such as The Cancer Genome Atlas (TCGA) have generated various -omics and clinical data on cancer. Many computational tools have been developed to facilitate the study of the molecular characterization of tumors using data from the TCGA. Alternative splicing of a gene produces splicing variants, and accumulating evidence has revealed its essential role in cancer-related processes, implying the urgent need to discover tumor-specific isoforms and uncover their potential functions in tumorigenesis.

RESULT: We developed TSVdb, a web-based tool, to explore alternative splicing based on TCGA samples with 30 clinical variables from 33 tumors. TSVdb has an integrated and well-proportioned interface for visualization of the clinical data, gene expression, usage of exons/junctions and splicing patterns. Researchers can interpret the isoform expression variations between or across clinical subgroups and estimate the relationships between isoforms and patient prognosis. TSVdb is available at http://www.tsvdb.com , and the source code is available at https://github.com/wenjie1991/TSVdb .

CONCLUSION: TSVdb will inspire oncologists and accelerate isoform-level advances in cancer research.}, } @article {pmid29843603, year = {2018}, author = {Grindflek, E and Hansen, MHS and Lien, S and van Son, M}, title = {Genome-wide association study reveals a QTL and strong candidate genes for umbilical hernia in pigs on SSC14.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {412}, pmid = {29843603}, issn = {1471-2164}, support = {174523//Research council of Norway/ ; }, mesh = {Animals ; *Genome-Wide Association Study ; Haplotypes ; Hernia, Umbilical/*genetics ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci/*genetics ; Swine ; }, abstract = {BACKGROUND: Umbilical hernia is one of the most prevalent congenital defect in pigs, causing economic losses and substantial animal welfare problems. Identification and implementation of genomic regions controlling umbilical hernia in breeding is of great interest to reduce incidences of hernia in commercial pig production. The aim of this study was to identify such regions and possibly identify causative variation affecting umbilical hernia in pigs. A case/control material consisting of 739 Norwegian Landrace pigs was collected and applied in a GWAS study with a genome-wide distributed panel of 60 K SNPs. Additionally candidate genes were sequenced to detect additional polymorphisms that were used for single SNP and haplotype association analyses in 453 of the pigs.

RESULTS: The GWAS in this report detected a highly significant region affecting umbilical hernia around 50 Mb on SSC14 (P < 0.0001) explaining up to 8.6% of the phenotypic variance of the trait. The region is rather broad and includes 62 significant SNPs in high linkage disequilibrium with each other. Targeted sequencing of candidate genes within the region revealed polymorphisms within the Leukemia inhibitory factor (LIF) and Oncostatin M (OSM) that were significantly associated with umbilical hernia (P < 0.001).

CONCLUSIONS: A highly significant QTL for umbilical hernia in Norwegian Landrace pigs was detected around 50 Mb on SSC14. Resequencing of candidate genes within the region revealed SNPs within LIF and OSM highly associated with the trait. However, because of extended LD within the region, studies in other populations and functional studies are needed to determine whether these variants are causal or not. Still without this knowledge, SNPs within the region can be used as genetic markers to reduce incidences of umbilical hernia in Norwegian Landrace pigs.}, } @article {pmid29843602, year = {2018}, author = {Keilwagen, J and Hartung, F and Paulini, M and Twardziok, SO and Grau, J}, title = {Combining RNA-seq data and homology-based gene prediction for plants, animals and fungi.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {189}, pmid = {29843602}, issn = {1471-2105}, abstract = {BACKGROUND: Genome annotation is of key importance in many research questions. The identification of protein-coding genes is often based on transcriptome sequencing data, ab-initio or homology-based prediction. Recently, it was demonstrated that intron position conservation improves homology-based gene prediction, and that experimental data improves ab-initio gene prediction.

RESULTS: Here, we present an extension of the gene prediction program GeMoMa that utilizes amino acid sequence conservation, intron position conservation and optionally RNA-seq data for homology-based gene prediction. We show on published benchmark data for plants, animals and fungi that GeMoMa performs better than the gene prediction programs BRAKER1, MAKER2, and CodingQuarry, and purely RNA-seq-based pipelines for transcript identification. In addition, we demonstrate that using multiple reference organisms may help to further improve the performance of GeMoMa. Finally, we apply GeMoMa to four nematode species and to the recently published barley reference genome indicating that current annotations of protein-coding genes may be refined using GeMoMa predictions.

CONCLUSIONS: GeMoMa might be of great utility for annotating newly sequenced genomes but also for finding homologs of a specific gene or gene family. GeMoMa has been published under GNU GPL3 and is freely available at http://www.jstacs.de/index.php/GeMoMa .}, } @article {pmid29843601, year = {2018}, author = {Arojju, SK and Conaghan, P and Barth, S and Milbourne, D and Casler, MD and Hodkinson, TR and Michel, T and Byrne, SL}, title = {Genomic prediction of crown rust resistance in Lolium perenne.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {35}, pmid = {29843601}, issn = {1471-2156}, support = {658031//H2020 Marie Sklodowska-Curie Actions (BE)/ ; RSF 11/S/109//Department of Agriculture, Food and the Marine (IE)/ ; }, abstract = {BACKGROUND: Genomic selection (GS) can accelerate genetic gains in breeding programmes by reducing the time it takes to complete a cycle of selection. Puccinia coronata f. sp lolli (crown rust) is one of the most widespread diseases of perennial ryegrass and can lead to reductions in yield, persistency and nutritional value. Here, we used a large perennial ryegrass population to assess the accuracy of using genome wide markers to predict crown rust resistance and to investigate the factors affecting predictive ability.

RESULTS: Using these data, predictive ability for crown rust resistance in the complete population reached a maximum of 0.52. Much of the predictive ability resulted from the ability of markers to capture genetic relationships among families within the training set, and reducing the marker density had little impact on predictive ability. Using permutation based variable importance measure and genome wide association studies (GWAS) to identify and rank markers enabled the identification of a small subset of SNPs that could achieve predictive abilities close to those achieved using the complete marker set.

CONCLUSION: Using a GWAS to identify and rank markers enabled a small panel of markers to be identified that could achieve higher predictive ability than the same number of randomly selected markers, and predictive abilities close to those achieved with the entire marker set. This was particularly evident in a sub-population characterised by having on-average higher genome-wide linkage disequilibirum (LD). Higher predictive abilities with selected markers over random markers suggests they are in LD with QTL. Accuracy due to genetic relationships will decay rapidly over generations whereas accuracy due to LD will persist, which is advantageous for practical breeding applications.}, } @article {pmid29843600, year = {2018}, author = {Zhu, S and Xu, M and Wang, H and Pan, H and Wang, G and Huang, M}, title = {Study of spontaneous mutations in the transmission of poplar chloroplast genomes from mother to offspring.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {411}, pmid = {29843600}, issn = {1471-2164}, support = {BK20150879//the Natural Science Foundation of JiangSu Province/ ; 2012BAD01B03//the 'Twelfth Five-Year' National Science and Technology Support Program/ ; 2014T70530//the China Postdoctoral Science Foundation Grant/ ; }, mesh = {DNA, Chloroplast/genetics ; Genome Size ; Genome, Chloroplast/*genetics ; Genotype ; *Mutation ; Polymorphism, Single Nucleotide ; Populus/*genetics ; }, abstract = {BACKGROUND: Chloroplasts have their own genomes, independent from nuclear genomes, that play vital roles in growth, which is a major targeted trait for genetic improvement in Populus. Angiosperm chloroplast genomes are maternally inherited, but the chloroplast' variation pattern of poplar at the single-base level during the transmission from mother to offspring remains unknown.

RESULTS: Here, we constructed high-quality and almost complete chloroplast genomes for three poplar clones, 'NL895' and its parents, 'I69' and 'I45', from the short-read datasets using multi-pass sequencing (15-16 times per clone) and ultra-high coverage (at least 8500× per clone), with the four-step strategy of Simulation-Assembly-Merging-Correction. Each of the three resulting chloroplast assemblies contained contigs covering > 99% of Populus trichocarpa chloroplast DNA as a reference. A total of 401 variant loci were identified by a hybrid strategy of genome comparison-based and mapping-based single nucleotide polymorphism calling. The genotypes of 94 variant loci were different among the three poplar clones. However, only 1 of the 94 loci was a missense mutation, which was located in the exon region of rpoC1 encoding the β' subunit of plastid-encoded RNA polymerase. The genotype of the loci in NL895 and its female parent (I69) was different from that of its male parent (I45).

CONCLUSIONS: This research provides resources for further chloroplast genomic studies of a F1 full-sibling family derived from a cross between I69 and I45, and will improve the application of chloroplast genomic information in modern Populus breeding programs.}, } @article {pmid29843599, year = {2018}, author = {Wu, Y and Liu, Y and Wang, Y and Shi, Y and Zhao, X}, title = {JCDSA: a joint covariate detection tool for survival analysis on tumor expression profiles.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {187}, pmid = {29843599}, issn = {1471-2105}, abstract = {BACKGROUND: Survival analysis on tumor expression profiles has always been a key issue for subsequent biological experimental validation. It is crucial how to select features which closely correspond to survival time. Furthermore, it is important how to select features which best discriminate between low-risk and high-risk group of patients. Common features derived from the two aspects may provide variable candidates for prognosis of cancer.

RESULTS: Based on the provided two-step feature selection strategy, we develop a joint covariate detection tool for survival analysis on tumor expression profiles. Significant features, which are not only consistent with survival time but also associated with the categories of patients with different survival risks, are chosen. Using the miRNA expression data (Level 3) of 548 patients with glioblastoma multiforme (GBM) as an example, miRNA candidates for prognosis of cancer are selected. The reliability of selected miRNAs using this tool is demonstrated by 100 simulations. Furthermore, It is discovered that significant covariates are not directly composed of individually significant variables.

CONCLUSIONS: Joint covariate detection provides a viewpoint for selecting variables which are not individually but jointly significant. Besides, it helps to select features which are not only consistent with survival time but also associated with prognosis risk. The software is available at http://bio-nefu.com/resource/jcdsa .}, } @article {pmid29843598, year = {2018}, author = {Perry, KD and Baker, GJ and Powis, KJ and Kent, JK and Ward, CM and Baxter, SW}, title = {Cryptic Plutella species show deep divergence despite the capacity to hybridize.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {77}, pmid = {29843598}, issn = {1471-2148}, support = {UA00146//University of Adelaide/International ; DAS00094//Grains Research and Development Corporation/International ; DAS00155//Grains Research and Development Corporation/International ; DAS00155//Grains Research and Development Corporation/International ; DAS00155//Grains Research and Development Corporation/International ; DP120100047//Australian Research Council/International ; FT140101303//Australian Research Council/International ; }, mesh = {Animals ; Australia ; Biological Assay ; Crosses, Genetic ; DNA, Mitochondrial/genetics ; Female ; Fertility ; *Genetic Variation ; Genetics, Population ; Geography ; Haplotypes/genetics ; Heterozygote ; *Hybridization, Genetic/drug effects ; Insecticide Resistance/drug effects/genetics ; Insecticides/toxicity ; Likelihood Functions ; Male ; Mitochondria/genetics ; Moths/*genetics/microbiology ; Phylogeny ; Species Specificity ; Sympatry ; Wolbachia/drug effects/physiology ; }, abstract = {BACKGROUND: Understanding genomic and phenotypic diversity among cryptic pest taxa has important implications for the management of pests and diseases. The diamondback moth, Plutella xylostella L., has been intensively studied due to its ability to evolve insecticide resistance and status as the world's most destructive pest of brassicaceous crops. The surprise discovery of a cryptic species endemic to Australia, Plutella australiana Landry & Hebert, raised questions regarding the distribution, ecological traits and pest status of the two species, the capacity for gene flow and whether specific management was required. Here, we collected Plutella from wild and cultivated brassicaceous plants from 75 locations throughout Australia and screened 1447 individuals to identify mtDNA lineages and Wolbachia infections. We genotyped genome-wide SNP markers using RADseq in coexisting populations of each species. In addition, we assessed reproductive compatibility in crossing experiments and insecticide susceptibility phenotypes using bioassays.

RESULTS: The two Plutella species coexisted on wild brassicas and canola crops, but only 10% of Plutella individuals were P. australiana. This species was not found on commercial Brassica vegetable crops, which are routinely sprayed with insecticides. Bioassays found that P. australiana was 19-306 fold more susceptible to four commonly-used insecticides than P. xylostella. Laboratory crosses revealed that reproductive isolation was incomplete but directionally asymmetric between the species. However, genome-wide nuclear SNPs revealed striking differences in genetic diversity and strong population structure between coexisting wild populations of each species. Nuclear diversity was 1.5-fold higher in P. australiana, yet both species showed limited variation in mtDNA. Infection with a single Wolbachia subgroup B strain was fixed in P. australiana, suggesting that a selective sweep contributed to low mtDNA diversity, while a subgroup A strain infected just 1.5% of P. xylostella.

CONCLUSIONS: Despite sympatric distributions and the capacity to hybridize, strong genomic and phenotypic divergence exists between these Plutella species that is consistent with contrasting colonization histories and reproductive isolation after secondary contact. Although P. australiana is a potential pest of brassicaceous crops, it is of secondary importance to P. xylostella.}, } @article {pmid29843597, year = {2018}, author = {Dai, W and Wang, Q and Zhao, F and Liu, J and Liu, H}, title = {Understanding the regulatory mechanisms of milk production using integrative transcriptomic and proteomic analyses: improving inefficient utilization of crop by-products as forage in dairy industry.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {403}, pmid = {29843597}, issn = {1471-2164}, support = {2016YFD0500503//National Key Research and Development Program of China/ ; 31372336//National Natural Science Foundations of China/ ; 31672447//National Natural Science Foundations of China/ ; }, mesh = {Animal Feed/analysis ; Animals ; Cattle ; Crops, Agricultural/*chemistry ; *Dairying ; Female ; *Gene Expression Profiling ; Gene Ontology ; *Industry ; Mammary Glands, Animal/drug effects/metabolism ; Medicago sativa/chemistry ; Milk/*drug effects/*metabolism ; *Proteomics ; Zea mays/chemistry ; }, abstract = {BACKGROUND: Bovine milk is an important nutrient source for humans. Forage plays a vital role in dairy husbandry via affecting milk quality and quantity. However, the differences in mammary metabolism of dairy cows fed different forages remain elucidated. In this study, we utilized transcriptomic RNA-seq and iTRAQ proteomic techniques to investigate and integrate the differences of molecular pathways and biological processes in the mammary tissues collected from 12 lactating cows fed corn stover (CS, low-quality, n = 6) and alfalfa hay (AH, high-quality, n = 6).

RESULTS: A total of 1631 differentially expressed genes (DEGs; 1046 up-regulated and 585 down-regulated) and 346 differentially expressed proteins (DEPs; 138 increased and 208 decreased) were detected in the mammary glands between the CS- and AH-fed animals. Expression patterns of 33 DEPs (18 increased and 15 decreased) were consistent with the expression of their mRNAs. Compared with the mammary gland of AH-fed cows, the marked expression changes found in the mammary gland of CS group were for genes involved in reduced mammary growth/development (COL4A2, MAPK3, IKBKB, LGALS3), less oxidative phosphorylation (ATPsynGL, ATP6VOA1, ATP5H, ATP6VOD1, NDUFC1), enhanced lipid uptake/metabolism (SLC27A6, FABP4, SOD2, ACADM, ACAT1, IDH1, SCP2, ECHDC1), more active fatty acid beta-oxidation (HMGCS1), less amino acid/protein transport (SLC38A2, SLC7A8, RAB5a, VPS18), reduced protein translation (RPS6, RPS12, RPS16, RPS19, RPS20, RPS27), more proteasome- (PSMC2, PSMC6, PSMD14, PSMA2, PSMA3) and ubiquitin-mediated protein degradation (UBE2B, UBE2H, KLHL9, HSPH1, DNAJA1 and CACYBP), and more protein disassembly-related enzymes (SEC63, DNAJC3, DNAJB1, DNAJB11 and DNAJC12).

CONCLUSION: Our results indicate that the lower milk production in the CS-fed dairy cows compared with the AH-fed cows was associated with a network of mammary gene expression changes, importantly, the prime factors include decreased energy metabolism, attenuated protein synthesis, enhanced protein degradation, and the lower mammary cell growth. The present study provides insights into the effects of the varying quality of forages on mammary metabolisms, which can help the improvement of strategies in feeding dairy cows with CS-based diet.}, } @article {pmid29843596, year = {2018}, author = {Babben, S and Schliephake, E and Janitza, P and Berner, T and Keilwagen, J and Koch, M and Arana-Ceballos, FA and Templer, SE and Chesnokov, Y and Pshenichnikova, T and Schondelmaier, J and Börner, A and Pillen, K and Ordon, F and Perovic, D}, title = {Association genetics studies on frost tolerance in wheat (Triticum aestivum L.) reveal new highly conserved amino acid substitutions in CBF-A3, CBF-A15, VRN3 and PPD1 genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {409}, pmid = {29843596}, issn = {1471-2164}, support = {0315953//BMBF/ ; #0324-2016-0001//ICG Russian Federation/ ; }, mesh = {*Amino Acid Substitution ; Cold Temperature ; *Conserved Sequence ; Haplotypes ; INDEL Mutation ; Linkage Disequilibrium ; Phenotype ; Plant Proteins/chemistry/*genetics ; Polymorphism, Single Nucleotide ; Triticum/*genetics/physiology ; }, abstract = {BACKGROUND: Understanding the genetic basis of frost tolerance (FT) in wheat (Triticum aestivum L.) is essential for preventing yield losses caused by frost due to cellular damage, dehydration and reduced metabolism. FT is a complex trait regulated by a number of genes and several gene families. Availability of the wheat genomic sequence opens new opportunities for exploring candidate genes diversity for FT. Therefore, the objectives of this study were to identity SNPs and insertion-deletion (indels) in genes known to be involved in frost tolerance and to perform association genetics analysis of respective SNPs and indels on FT.

RESULTS: Here we report on the sequence analysis of 19 candidate genes for FT in wheat assembled using the Chinese Spring IWGSC RefSeq v1.0. Out of these, the tandem duplicated C-repeat binding factors (CBF), i.e. CBF-A3, CBF-A5, CBF-A10, CBF-A13, CBF-A14, CBF-A15, CBF-A18, the vernalisation response gene VRN-A1, VRN-B3, the photoperiod response genes PPD-B1 and PPD-D1 revealed association to FT in 235 wheat cultivars. Within six genes (CBF-A3, CBF-A15, VRN-A1, VRN-B3, PPD-B1 and PPD-D1) amino acid (AA) substitutions in important protein domains were identified. The amino acid substitution effect in VRN-A1 on FT was confirmed and new AA substitutions in CBF-A3, CBF-A15, VRN-B3, PPD-B1 and PPD-D1 located at highly conserved sites were detected. Since these results rely on phenotypic data obtained at five locations in 2 years, detection of significant associations of FT to AA changes in CBF-A3, CBF-A15, VRN-A1, VRN-B3, PPD-B1 and PPD-D1 may be exploited in marker assisted breeding for frost tolerance in winter wheat.

CONCLUSIONS: A set of 65 primer pairs for the genes mentioned above from a previous study was BLASTed against the IWGSC RefSeq resulting in the identification of 39 primer combinations covering the full length of 19 genes. This work demonstrates the usefulness of the IWGSC RefSeq in specific primer development for highly conserved gene families in hexaploid wheat and, that a candidate gene association genetics approach based on the sequence data is an efficient tool to identify new alleles of genes important for the response to abiotic stress in wheat.}, } @article {pmid29843595, year = {2018}, author = {Su, S and Wang, Y and Wang, H and Huang, W and Chen, J and Xing, J and Xu, P and Yuan, X and Huang, C and Zhou, Y}, title = {Comparative expression analysis identifies the respiratory transition-related miRNAs and their target genes in tissues of metamorphosing Chinese giant salamander (Andrias davidianus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {406}, pmid = {29843595}, issn = {1471-2164}, support = {2016RC-LX03//Central Public-interest Scientific Institution Basal Research Fund, Chinese Academy of Fishery Sciences (CAFS)/ ; }, mesh = {Animals ; *Gene Expression Profiling ; Gene Regulatory Networks ; Metamorphosis, Biological/*genetics ; MicroRNAs/*genetics ; Molecular Sequence Annotation ; Respiration/*genetics ; Urodela/*genetics/growth & development/*physiology ; }, abstract = {BACKGROUND: Chinese giant salamander (Andrias davidianus) undergoes a metamorphosis from aquatic larvae to terrestrial adults, with concomitant transfer of respiration from gills to lungs prior to metamorphosis. These two tissues, as well as skin, were sampled to identify the differentially expressed miRNAs.

RESULTS: High-coverage reference transcriptome was generated from combined gill, lung and skin tissues of metamorphosing juveniles, and lung tissue of adults: 86,282 unigenes with total length of approximately 77,275,634 bp and N50 of 1732 bp were obtained. Among these, 13,246 unigenes were assigned to 288 pathways. To determine the possible involvement of miRNAs in the respiratory transition, small RNA libraries were sequenced; 282 miRNAs were identified, 65 among which were known and 217 novel. Based on the hierarchical clustering analysis, the twelve studied samples were classified into three major clusters using differentially expressed miRNAs. We have validated ten differentially expressed miRNAs and some of their related target genes using qPCR. These results largely corroborated the results of transcriptomic and miRNA analyses. Finally, an miRNA-gene-network was constructed. Among them, two miRNAs with target genes related to oxygen sensing were differentially expressed between gill and lung tissues. Three miRNAs were differentially expressed between the lungs of larvae and lungs of adults.

CONCLUSIONS: This study provides the first large-scale miRNA expression profile overview during the respiration transition from gills to lungs in Chinese giant salamander. Five differentially expressed miRNAs and their target genes were identified among skin, gill and lung tissues. These results suggest that miRNA profiles in respiratory tissues play an important role in the regulation of respiratory transition.}, } @article {pmid29843594, year = {2018}, author = {Kaltenegger, E and Leng, S and Heyl, A}, title = {The effects of repeated whole genome duplication events on the evolution of cytokinin signaling pathway.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {76}, pmid = {29843594}, issn = {1471-2148}, mesh = {Base Sequence ; Cytokinins/*genetics ; Embryophyta/genetics ; *Evolution, Molecular ; Gene Dosage ; *Gene Duplication ; Genes, Duplicate ; *Genome, Plant ; Histidine/metabolism ; Likelihood Functions ; Phylogeny ; Plant Proteins/genetics/metabolism ; Polyploidy ; Receptors, Cell Surface/genetics ; *Signal Transduction ; }, abstract = {BACKGROUND: It is thought that after whole-genome duplications (WGDs), a large fraction of the duplicated gene copies is lost over time while few duplicates are retained. Which factors promote survival or death of a duplicate remains unclear and the underlying mechanisms are poorly understood. According to the model of gene dosage balance, genes encoding interacting proteins are predicted to be preferentially co-retained after WGDs. Among these are genes encoding proteins involved in complexes or in signal transduction.

RESULTS: We have investigated the way that repeated WGDs during land plant evolution have affected cytokinin signaling to study patterns of gene duplicability and co-retention in this important signal transduction pathway. Through the integration of phylogenetic analyses with comparisons of genome collinearity, we have found that signal input mediated by cytokinin receptors proved to be highly conserved over long evolutionary time-scales, with receptors showing predominantly gene loss after repeated WGDs. However, the downstream elements, e,g. response regulators, were mainly retained after WGDs and thereby formed gene families in most plant lineages.

CONCLUSIONS: Gene dosage balance between the interacting components indicated by co-retention after WGDs seems to play a minor role in the evolution of cytokinin signaling pathway. Overall, core genes of cytokinin signaling show a highly heterogeneous pattern of gene retention after WGD, reflecting complex relationships between the various factors that shape the long-term fate of a duplicated gene.}, } @article {pmid29843593, year = {2018}, author = {Zeng, C and Fukunaga, T and Hamada, M}, title = {Identification and analysis of ribosome-associated lncRNAs using ribosome profiling data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {414}, pmid = {29843593}, issn = {1471-2164}, support = {JP17K20032//Ministry of Education, Culture, Sports, Science and Technology/ ; JP16H05879//Ministry of Education, Culture, Sports, Science and Technology/ ; JP16H01318//Ministry of Education, Culture, Sports, Science and Technology/ ; JP16H02484//Ministry of Education, Culture, Sports, Science and Technology/ ; }, mesh = {Gene Expression Profiling ; HeLa Cells ; Humans ; RNA, Long Noncoding/*genetics ; Ribosomes/*genetics ; *Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Although the number of discovered long non-coding RNAs (lncRNAs) has increased dramatically, their biological roles have not been established. Many recent studies have used ribosome profiling data to assess the protein-coding capacity of lncRNAs. However, very little work has been done to identify ribosome-associated lncRNAs, here defined as lncRNAs interacting with ribosomes related to protein synthesis as well as other unclear biological functions.

RESULTS: On average, 39.17% of expressed lncRNAs were observed to interact with ribosomes in human and 48.16% in mouse. We developed the ribosomal association index (RAI), which quantifies the evidence for ribosomal associability of lncRNAs over various tissues and cell types, to catalog 691 and 409 lncRNAs that are robustly associated with ribosomes in human and mouse, respectively. Moreover, we identified 78 and 42 lncRNAs with a high probability of coding peptides in human and mouse, respectively. Compared with ribosome-free lncRNAs, ribosome-associated lncRNAs were observed to be more likely to be located in the cytoplasm and more sensitive to nonsense-mediated decay.

CONCLUSION: Our results suggest that RAI can be used as an integrative and evidence-based tool for distinguishing between ribosome-associated and free lncRNAs, providing a valuable resource for the study of lncRNA functions.}, } @article {pmid29843592, year = {2018}, author = {El-Mogy, M and Lam, B and Haj-Ahmad, TA and McGowan, S and Yu, D and Nosal, L and Rghei, N and Roberts, P and Haj-Ahmad, Y}, title = {Diversity and signature of small RNA in different bodily fluids using next generation sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {408}, pmid = {29843592}, issn = {1471-2164}, mesh = {Adult ; Body Fluids/*metabolism ; Female ; *Genetic Variation ; *High-Throughput Nucleotide Sequencing ; Humans ; Male ; RNA, Small Untranslated/*genetics ; *Sequence Analysis, RNA ; Young Adult ; }, abstract = {BACKGROUND: Small RNAs are critical components in regulating various cellular pathways. These molecules may be tissue-associated or circulating in bodily fluids and have been shown to associate with different tumors. Next generation sequencing (NGS) on small RNAs is a powerful tool for profiling and discovery of microRNAs (miRNAs).

RESULTS: In this study, we isolated total RNA from various bodily fluids: blood, leukocytes, serum, plasma, saliva, cell-free saliva, urine and cell-free urine. Next, we used Illumina's NGS platform and intensive bioinformatics analysis to investigate the distribution and signature of small RNAs in the various fluids. Successful NGS was accomplished despite the variations in RNA concentrations among the different fluids. Among the fluids studied, blood and plasma were found to be the most promising fluids for small RNA profiling as well as novel miRNA prediction. Saliva and urine yielded lower numbers of identifiable molecules and therefore were less reliable in small RNA profiling and less useful in predicting novel molecules. In addition, all fluids shared many molecules, including 139 miRNAs, the most abundant tRNAs, and the most abundant piwi-interacting RNAs (piRNAs). Fluids of similar origin (blood, urine or saliva) displayed closer clustering, while each fluid still retains its own characteristic signature based on its unique molecules and its levels of the common molecules. Donor urine samples showed sex-dependent differential clustering, which may prove useful for future studies.

CONCLUSIONS: This study shows the successful clustering and unique signatures of bodily fluids based on their miRNA, tRNA and piRNA content. With this information, cohorts may be differentiated based on multiple molecules from each small RNA class by a multidimensional assessment of the overall molecular signature.}, } @article {pmid29843591, year = {2018}, author = {Aria, C and Caron, JB}, title = {Correction to: Mandibulate convergence in an armoured Cambrian stem chelicerate.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {78}, pmid = {29843591}, issn = {1471-2148}, abstract = {The original article [1] had 4 paragraphs which contained erroneous information. In this correction article the correct and incorrect information is shown.}, } @article {pmid29843590, year = {2018}, author = {Sang, S and Yang, Z and Wang, L and Liu, X and Lin, H and Wang, J}, title = {SemaTyP: a knowledge graph based literature mining method for drug discovery.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {193}, pmid = {29843590}, issn = {1471-2105}, abstract = {BACKGROUND: Drug discovery is the process through which potential new medicines are identified. High-throughput screening and computer-aided drug discovery/design are the two main drug discovery methods for now, which have successfully discovered a series of drugs. However, development of new drugs is still an extremely time-consuming and expensive process. Biomedical literature contains important clues for the identification of potential treatments. It could support experts in biomedicine on their way towards new discoveries.

METHODS: Here, we propose a biomedical knowledge graph-based drug discovery method called SemaTyP, which discovers candidate drugs for diseases by mining published biomedical literature. We first construct a biomedical knowledge graph with the relations extracted from biomedical abstracts, then a logistic regression model is trained by learning the semantic types of paths of known drug therapies' existing in the biomedical knowledge graph, finally the learned model is used to discover drug therapies for new diseases.

RESULTS: The experimental results show that our method could not only effectively discover new drug therapies for new diseases, but also could provide the potential mechanism of action of the candidate drugs.

CONCLUSIONS: In this paper we propose a novel knowledge graph based literature mining method for drug discovery. It could be a supplementary method for current drug discovery methods.}, } @article {pmid29843589, year = {2018}, author = {Zhao, S and Li, CI and Guo, Y and Sheng, Q and Shyr, Y}, title = {RnaSeqSampleSize: real data based sample size estimation for RNA sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {191}, pmid = {29843589}, issn = {1471-2105}, support = {P30 CA068485/CA/NCI NIH HHS/United States ; P50 CA095103/CA/NCI NIH HHS/United States ; P50 CA098131/CA/NCI NIH HHS/United States ; U24 CA163056/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: One of the most important and often neglected components of a successful RNA sequencing (RNA-Seq) experiment is sample size estimation. A few negative binomial model-based methods have been developed to estimate sample size based on the parameters of a single gene. However, thousands of genes are quantified and tested for differential expression simultaneously in RNA-Seq experiments. Thus, additional issues should be carefully addressed, including the false discovery rate for multiple statistic tests, widely distributed read counts and dispersions for different genes.

RESULTS: To solve these issues, we developed a sample size and power estimation method named RnaSeqSampleSize, based on the distributions of gene average read counts and dispersions estimated from real RNA-seq data. Datasets from previous, similar experiments such as the Cancer Genome Atlas (TCGA) can be used as a point of reference. Read counts and their dispersions were estimated from the reference's distribution; using that information, we estimated and summarized the power and sample size. RnaSeqSampleSize is implemented in R language and can be installed from Bioconductor website. A user friendly web graphic interface is provided at http://cqs.mc.vanderbilt.edu/shiny/RnaSeqSampleSize/ .

CONCLUSIONS: RnaSeqSampleSize provides a convenient and powerful way for power and sample size estimation for an RNAseq experiment. It is also equipped with several unique features, including estimation for interested genes or pathway, power curve visualization, and parameter optimization.}, } @article {pmid29843588, year = {2018}, author = {Wittich, HC and Seeland, M and Wäldchen, J and Rzanny, M and Mäder, P}, title = {Recommending plant taxa for supporting on-site species identification.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {190}, pmid = {29843588}, issn = {1471-2105}, abstract = {BACKGROUND: Predicting a list of plant taxa most likely to be observed at a given geographical location and time is useful for many scenarios in biodiversity informatics. Since efficient plant species identification is impeded mainly by the large number of possible candidate species, providing a shortlist of likely candidates can help significantly expedite the task. Whereas species distribution models heavily rely on geo-referenced occurrence data, such information still remains largely unused for plant taxa identification tools.

RESULTS: In this paper, we conduct a study on the feasibility of computing a ranked shortlist of plant taxa likely to be encountered by an observer in the field. We use the territory of Germany as case study with a total of 7.62M records of freely available plant presence-absence data and occurrence records for 2.7k plant taxa. We systematically study achievable recommendation quality based on two types of source data: binary presence-absence data and individual occurrence records. Furthermore, we study strategies for aggregating records into a taxa recommendation based on location and date of an observation.

CONCLUSION: We evaluate recommendations using 28k geo-referenced and taxa-labeled plant images hosted on the Flickr website as an independent test dataset. Relying on location information from presence-absence data alone results in an average recall of 82%. However, we find that occurrence records are complementary to presence-absence data and using both in combination yields considerably higher recall of 96% along with improved ranking metrics. Ultimately, by reducing the list of candidate taxa by an average of 62%, a spatio-temporal prior can substantially expedite the overall identification problem.}, } @article {pmid29809123, year = {2018}, author = {Huber, KJ and Overmann, J}, title = {Vicinamibacteraceae fam. nov., the first described family within the subdivision 6 Acidobacteria.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2331-2334}, doi = {10.1099/ijsem.0.002841}, pmid = {29809123}, issn = {1466-5034}, mesh = {Acidobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Acidobacteria constitute a globally widespread phylum and mainly inhabit soil environments. Despite their high abundance and activity, only 60 species from seven of the 26 acidobacterial subdivisions (sds; corresponding to class level) are (validly) described. Thus, only a low number of higher taxonomic ranks is currently distinguished within the Acidobacteria. Additionally, the distribution of the known acidobacterial species within the described families of the Acidobacteriaceae (sd1), Bryobacteraceae (sd3), Blastocatellaceae (sd4), Pyrinomonadaceae (sd4), Holophagaceae (sd8) and Acanthopleuribacteraceae (sd8) is extremely biased as most strains are affiliated with the Acidobacteriaceae. Members of this family are characteristic for acidic soils. In contrast, culture-independent analysis of microbial communities worldwide revealed that sd6 Acidobacteria prevail in soils with neutral pH. To improve the existing acidobacterial taxonomy, we here formally describe the first family within sd6 Acidobacteria, the Vicinamibacteraceae. Members of the Vicinamibacteraceae are aerobic, neutrophilic, psychrotolerant to mesophilic chemoheterotrophs. Their cells stain Gram-negative, do not form capsules or spores, and are non-motile. They occur as single cells or in aggregates and divide by binary fission. Growth occurs on sugars or complex proteinaceous compounds. MK-8 is the major quinone. Major fatty acids are iso-C15 : 0, summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), C18 : 1ω7c or ω9c, iso-C17 : 1ω9c, C16 : 0 and iso-C17 : 0. Diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and phosphatidylglycerol are the major polar lipids. Unidentified glycolipids or unknown phospholipids might also be present. The G+C content of the DNA ranges from 64.7 to 65.9 mol%. Within the Vicinamibacteraceae fam. nov., Vicinamibacter and Luteitalea are the only genera described so far.}, } @article {pmid29809122, year = {2018}, author = {Šibanc, N and Zalar, P and Schroers, HJ and Zajc, J and Pontes, A and Sampaio, JP and Maček, I}, title = {Occultifur mephitis f.a., sp. nov. and other yeast species from hypoxic and elevated CO2 mofette environments.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2285-2298}, doi = {10.1099/ijsem.0.002824}, pmid = {29809122}, issn = {1466-5034}, mesh = {Basidiomycota/classification ; Candida/classification ; Carbon Dioxide/*chemistry ; DNA, Fungal/genetics ; Forests ; Mycological Typing Techniques ; Natural Springs/*microbiology ; *Phylogeny ; Pichia ; Portugal ; Saccharomycetales/classification ; Sequence Analysis, DNA ; Slovenia ; *Soil Microbiology ; Yeasts/*classification/genetics/isolation & purification ; }, abstract = {An inventory of culturable yeasts from the soil and water of natural CO2 springs (mofettes) in northeast Slovenia is presented. In mofettes, CO2 of geological origin reaches the soil surface causing temporarily and spatially stable hypoxic environments in soil and water. In total, 142 yeast strains were isolated and identified from high CO2 and control meadow soil, meadow ground-water, forest pond and stream water. All water locations showed below-ground CO2 release. They were assigned to six basidiomycetous yeast genera (six species) and 11 ascomycetous genera (18 species). All ascomycetous yeasts, with the exception of Debaryomyces hansenii, were able to grow under elevated CO2 and fermented glucose. Candida sophiae-reginae, Pichia fermentans and Candida vartiovaarae were the dominating species in meadow and forest high CO2 exposed water. Meyerozyma guilliermondii and Wickerhamomyces anomalus predominated in high CO2 exposed soils. Using high dilution plating of a mofette soil sample, four strains of an unknown basidiomycetous species were isolated and are here newly described as Occultifur mephitis based on molecular phylogenetic and phenotypic criteria. The type strain of Occultifur mephitis is EXF-6436T[CBS 14611=PYCC 7049, LT594852 (D1/D2), KX929055 (ITS)]. An additional three isolated strains are EXF-6437 (LT594853, KX929056), EXF-6473 (LT594863, KX929057) and EXF-6482 (LT594867, KX929054), as well as a strain reported from previous studies isolated from a leaf of Cistus albidus in Portugal (CBS 10223=PYCC 6067), EU002842 (D1/D2), KY308183 (ITS).}, } @article {pmid29809121, year = {2018}, author = {Wirth, JS and Whitman, WB}, title = {Phylogenomic analyses of a clade within the roseobacter group suggest taxonomic reassignments of species of the genera Aestuariivita, Citreicella, Loktanella, Nautella, Pelagibaca, Ruegeria, Thalassobius, Thiobacimonas and Tropicibacter, and the proposal of six novel genera.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2393-2411}, doi = {10.1099/ijsem.0.002833}, pmid = {29809121}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification ; Sequence Analysis, DNA ; }, abstract = {Roseobacters are a diverse and globally abundant group of Alphaproteobacteria within the Rhodobacteraceae family. Recent studies and the cophenetic correlations suggest that the 16S rRNA genes are poor phylogenetic markers within this group. In contrast, the cophenetic correlation coefficients of the core-gene average amino acid identity (cAAI) and RpoC protein sequences are high and likely more predictive of relationships. A maximum-likelihood phylogenetic tree calculated from 53 core genes demonstrated that some of the current genera were either polyphyletic or paraphyletic. The boundaries of bacterial genera were redefined based upon the cAAI, the percentage of conserved proteins, and phenotypic characteristics and resulted in the following taxonomic proposals. Loktanella vestfoldensis, Loktanella litorea, Loktanella maricola, Loktanella maritima, Loktanella rosea, Loktanella sediminilitoris, Loktanella tamlensis, and Roseobacter sp. CCS2 should be reclassified into the novel genus Yoonia. Loktanella hongkongensis, Loktanella aestuariicola, Loktanella cinnabarina, Loktanella pyoseonensis, Loktanellasoe soekkakensis and Loktanella variabilis should be reclassified in the novel genus Limimaricola. Loktanella koreensis and Loktanella sediminum should be reclassified in the novel genus Cognatiyoonia. Loktanella marina should be reclassified in the novel genus Flavimaricola. Aestuariivita atlantica should be reclassified in the novel genus Pseudaestuariivita. Thalassobius maritima should be reclassified in the novel genus Cognatishimia. Similarly, Ruegeria mobilis, Ruegeria scottomollicae, Ruegeria sp. TM1040 and Tropicibacter multivorans should be reclassified in the genus Epibacterium. Tropicibacter litoreus and Tropicibacter mediterraneus should be reclassified in the genus Ruegeria. Thalassobius abyssi and Thalassobius aestuarii should be reclassified in the genus Shimia. Citreicella aestuarii, Citreicella manganoxidans, Citreicella marina, Citreicella thiooxidans, Pelagibaca bermudensis and Thiobacimonas profunda should be reclassified in the genus Salipiger. Nautella italica should be reclassified in the genus Phaeobacter. Because these proposals to reclassify the type and all others species of Citreicella, Nautella, Pelagibaca and Thiobacimonas, these genera are not used in this taxonomy.}, } @article {pmid29809120, year = {2018}, author = {Kim, SH and Kim, JG and Jung, MY and Kim, SJ and Gwak, JH and Yu, WJ and Roh, SW and Kim, YH and Rhee, SK}, title = {Ketobacter alkanivorans gen. nov., sp. nov., an n-alkane-degrading bacterium isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2258-2264}, doi = {10.1099/ijsem.0.002823}, pmid = {29809120}, issn = {1466-5034}, mesh = {Alcanivoraceae/*classification/genetics/isolation & purification ; Alkanes/*metabolism ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {Strain GI5T was isolated from a surface seawater sample collected from Garorim Bay (West Sea, Republic of Korea). The isolated strain was aerobic, Gram-stain-negative, rod-shaped, motile by means of a polar flagellum, negative for catalase and weakly positive for oxidase. The optimum growth pH, salinity and temperature were determined to be pH 7.5-8.0, 3 % NaCl (w/v) and 25 °C, respectively; the growth ranges were pH 6.0-9.0, 1-7 % NaCl (w/v) and 18-40 °C. The results of phylogenetic analysis of 16S rRNA gene sequences indicated that GI5T clustered within the family Alcanivoracaceae, and most closely with Alcanivorax dieseloleiB-5T and Alcanivorax marinusR8-12T (91.9 % and 91.6 % similarity, respectively). The major cellular fatty acids in GI5T were C18 : 1ω7c/C18 : 1ω6c (44.45 %), C16 : 1ω6c/C16 : 1ω7c (14.17 %) and C16 : 0 (10.19 %); this profile was distinct from those of the closely related species. The major respiratory quinone of GI5T was Q-8. The main polar lipids were phosphatidylethanolamine and phosphatidylglycerol. Two putative alkane hydroxylase (alkB) genes were identified in GI5T. The G+C content of the genomic DNA of GI5T was determined to be 51.2 mol%. On the basis of the results of phenotypic, chemotaxonomic and phylogenetic studies, strain GI5T represents a novel species of a novel genus of the family Alcanivoracaceae, for which we propose the name Ketobacter alkanivorans gen. nov., sp. nov.; the type strain is GI5T (=KCTC 52659T=JCM 31835T).}, } @article {pmid29808616, year = {2018}, author = {Cole, GL and Endler, JA}, title = {Change in male coloration associated with artificial selection on foraging colour preference.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1227-1238}, doi = {10.1111/jeb.13300}, pmid = {29808616}, issn = {1420-9101}, abstract = {Sensory drive proposes that natural selection on nonmating behaviours (e.g. foraging preferences) alters sensory system properties and results in a correlated effect on mating preferences and subsequently sexual traits. In colour-based systems, we can test this by selecting on nonmating colour preferences and testing for responses in colour-based female preferences and male sexual coloration. In guppies (Poecilia reticulata), individual functional links of sensory drive have been demonstrated providing an opportunity to test the process over more than one link. We measured male coloration and female preferences in populations previously artificially selected for colour-based foraging behaviour towards two colours, red and blue. We found associated changes in male coloration in the expected direction as well as weak changes in female preferences. Our results can be explained by a correlated response in female preferences due to artificial selection on foraging preferences that are mediated by a shared sensory system or by other mechanisms such as colour avoidance, pleiotropy or social experiences. This is the first experimental evidence that selection on a nonmating behaviour can affect male coloration and, more weakly, female preferences.}, } @article {pmid29808579, year = {2018}, author = {Melo Clavijo, J and Donath, A and Serôdio, J and Christa, G}, title = {Polymorphic adaptations in metazoans to establish and maintain photosymbioses.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {2006-2020}, doi = {10.1111/brv.12430}, pmid = {29808579}, issn = {1469-185X}, abstract = {Mutualistic symbioses are common throughout the animal kingdom. Rather unusual is a form of symbiosis, photosymbiosis, where animals are symbiotic with photoautotrophic organisms. Photosymbiosis is found among sponges, cnidarians, flatworms, molluscs, ascidians and even some amphibians. Generally the animal host harbours a phototrophic partner, usually a cyanobacteria or a unicellular alga. An exception to this rule is found in some sea slugs, which only retain the chloroplasts of the algal food source and maintain them photosynthetically active in their own cytosol - a phenomenon called 'functional kleptoplasty'. Research has focused largely on the biodiversity of photosymbiotic species across a range of taxa. However, many questions with regard to the evolution of the ability to establish and maintain a photosymbiosis are still unanswered. To date, attempts to understand genome adaptations which could potentially lead to the evolution of photosymbioses have only been performed in cnidarians. This knowledge gap for other systems is mainly due to a lack of genetic information, both for non-symbiotic and symbiotic species. Considering non-photosymbiotic species is, however, important to understand the factors that make symbiotic species so unique. Herein we provide an overview of the diversity of photosymbioses across the animal kingdom and discuss potential scenarios for the evolution of this association in different lineages. We stress that the evolution of photosymbiosis is probably based on genome adaptations, which (i) lead to recognition of the symbiont to establish the symbiosis, and (ii) are needed to maintain the symbiosis. We hope to stimulate research involving sequencing the genomes of various key taxa to increase the genomic resources needed to understand the most fundamental question: how have animals evolved the ability to establish and maintain a photosymbiosis?}, } @article {pmid29808578, year = {2018}, author = {Loreto, RG and Araújo, JPM and Kepler, RM and Fleming, KR and Moreau, CS and Hughes, DP}, title = {Evidence for convergent evolution of host parasitic manipulation in response to environmental conditions.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {10}, pages = {2144-2155}, doi = {10.1111/evo.13489}, pmid = {29808578}, issn = {1558-5646}, support = {IOS-1558062//Division of Integrative Organismal Systems/ ; BEX6203-10-8//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; R01 GM116927-02//National Institute of General Medical Sciences/ ; }, abstract = {Environmental conditions exert strong selection on animal behavior. We tested the hypothesis that the altered behavior of hosts due to parasitic manipulation is also subject to selection imposed by changes in environmental conditions over time. Our model system is ants manipulated by parasitic fungi to bite onto vegetation. We analyzed the correlation between forest type (tropical vs. temperate) and the substrate where the host bites (biting substrate: leaf vs. twigs), the time required for the fungi to reach reproductive maturity, and the phylogenetic relationship among specimens from tropical and temperate forests from different parts of the globe. We show that fungal development in temperate forests is longer than the period of time leaves are present and the ants are manipulated to bite twigs. When biting twigs, 90% of the dead ants we examined had their legs wrapped around twigs, which appears to provide better attachment to the plant. Ancestral state character reconstruction suggests that leaf biting is the ancestral trait and that twig biting is a convergent trait in temperate regions of the globe. These three lines of evidence suggest that changes in environmental conditions have shaped the manipulative behavior of the host by its parasite.}, } @article {pmid29808568, year = {2018}, author = {Iglesias, TL and Dornburg, A and Warren, DL and Wainwright, PC and Schmitz, L and Economo, EP}, title = {Eyes Wide Shut: the impact of dim-light vision on neural investment in marine teleosts.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1082-1092}, doi = {10.1111/jeb.13299}, pmid = {29808568}, issn = {1420-9101}, abstract = {Understanding how organismal design evolves in response to environmental challenges is a central goal of evolutionary biology. In particular, assessing the extent to which environmental requirements drive general design features among distantly related groups is a major research question. The visual system is a critical sensory apparatus that evolves in response to changing light regimes. In vertebrates, the optic tectum is the primary visual processing centre of the brain and yet it is unclear how or whether this structure evolves while lineages adapt to changes in photic environment. On one hand, dim-light adaptation is associated with larger eyes and enhanced light-gathering power that could require larger information processing capacity. On the other hand, dim-light vision may evolve to maximize light sensitivity at the cost of acuity and colour sensitivity, which could require less processing power. Here, we use X-ray microtomography and phylogenetic comparative methods to examine the relationships between diel activity pattern, optic morphology, trophic guild and investment in the optic tectum across the largest radiation of vertebrates-teleost fishes. We find that despite driving the evolution of larger eyes, enhancement of the capacity for dim-light vision generally is accompanied by a decrease in investment in the optic tectum. These findings underscore the importance of considering diel activity patterns in comparative studies and demonstrate how vision plays a role in brain evolution, illuminating common design principles of the vertebrate visual system.}, } @article {pmid29808565, year = {2018}, author = {Hrček, J and Parker, BJ and McLean, AHC and Simon, JC and Mann, CM and Godfray, HCJ}, title = {Hosts do not simply outsource pathogen resistance to protective symbionts.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13512}, pmid = {29808565}, issn = {1558-5646}, abstract = {Microbial symbionts commonly protect their hosts from natural enemies, but it is unclear how protective symbionts influence the evolution of host immunity to pathogens. One possibility is that 'extrinsic' protection provided by symbionts allows hosts to reduce investment in 'intrinsic' immunological resistance mechanisms. We tested this idea using pea aphids (Acyrthosiphon pisum) and their facultative bacterial symbionts that increase host resistance to the fungal pathogen Pandora neoaphidis. The pea aphid taxon is composed of multiple host plant associated populations called biotypes, which harbor characteristic communities of symbionts. We found that biotypes that more frequently carry protective symbionts have higher, rather than lower, levels of intrinsic resistance. Within a biotype there was no difference in intrinsic resistance between clones that did and did not carry a protective symbiont. The host plant on which an aphid feeds did not strongly influence intrinsic resistance. We describe a simple conceptual model of the interaction between intrinsic and extrinsic resistance and suggest that our results may be explained by selection favoring both the acquisition of protective symbionts and enhanced intrinsic resistance in habitats with high pathogen pressure. Such combined protection is potentially more robust than intrinsic resistance alone.}, } @article {pmid29808505, year = {2018}, author = {García-Navas, V and Westerman, M}, title = {Niche conservatism and phylogenetic clustering in a tribe of arid-adapted marsupial mice, the Sminthopsini.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1204-1215}, doi = {10.1111/jeb.13297}, pmid = {29808505}, issn = {1420-9101}, abstract = {The progressive expansion of the Australian arid zone during the last 20 Ma appears to have spurred the diversification of several families of plants, vertebrates and invertebrates, yet such taxonomic groups appear to show limited niche radiation. Here, we test whether speciation is associated with niche conservatism (constraints on ecological divergence) or niche divergence in a tribe of marsupial mice (Sminthopsini; 23 taxa) that includes the most speciose genus of living dasyurids, the sminthopsins. To that end, we integrated phylogenetic data with ecological niche modelling, to enable us to reconstruct the evolution of climatic suitability within Sminthopsini. Niche overlap among species was low-moderate (but generally higher than expected given environmental background similarity), and the degree of phylogenetic clustering increased with aridity. Climatic niche reconstruction illustrates that there has been little apparent evolution of climatic tolerance within clades. Accordingly, climatic disparity tends to be accumulated among clades, suggesting considerable niche conservatism. Our results also indicate that evolution of climatic tolerances has been heterogeneous across different dimensions of climate (temperature vs. precipitation) and across phylogenetic clusters (Sminthopsis murina group vs. other groups). Although some results point to the existence of shifts in climatic niches during the speciation of sminthopsins, our study provides evidence for substantial phylogenetic niche conservatism in the group. We conclude that niche diversification had a low impact on the speciation of this tribe of small, but highly mobile marsupials.}, } @article {pmid29808031, year = {2018}, author = {Perino, M and van Mierlo, G and Karemaker, ID and van Genesen, S and Vermeulen, M and Marks, H and van Heeringen, SJ and Veenstra, GJC}, title = {MTF2 recruits Polycomb Repressive Complex 2 by helical-shape-selective DNA binding.}, journal = {Nature genetics}, volume = {50}, number = {7}, pages = {1002-1010}, doi = {10.1038/s41588-018-0134-8}, pmid = {29808031}, issn = {1546-1718}, abstract = {ABSTACT: Polycomb-mediated repression of gene expression is essential for development, with a pivotal role played by trimethylation of histone H3 lysine 27 (H3K27me3), which is deposited by Polycomb Repressive Complex 2 (PRC2). The mechanism by which PRC2 is recruited to target genes has remained largely elusive, particularly in vertebrates. Here we demonstrate that MTF2, one of the three vertebrate homologs of Drosophila melanogaster Polycomblike, is a DNA-binding, methylation-sensitive PRC2 recruiter in mouse embryonic stem cells. MTF2 directly binds to DNA and is essential for recruitment of PRC2 both in vitro and in vivo. Genome-wide recruitment of the PRC2 catalytic subunit EZH2 is abrogated in Mtf2 knockout cells, resulting in greatly reduced H3K27me3 deposition. MTF2 selectively binds regions with a high density of unmethylated CpGs in a context of reduced helix twist, which distinguishes target from non-target CpG islands. These results demonstrate instructive recruitment of PRC2 to genomic targets by MTF2.}, } @article {pmid29808030, year = {2018}, author = {Zierer, J and Jackson, MA and Kastenmüller, G and Mangino, M and Long, T and Telenti, A and Mohney, RP and Small, KS and Bell, JT and Steves, CJ and Valdes, AM and Spector, TD and Menni, C}, title = {The fecal metabolome as a functional readout of the gut microbiome.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {790-795}, pmid = {29808030}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {The human gut microbiome plays a key role in human health 1 , but 16S characterization lacks quantitative functional annotation 2 . The fecal metabolome provides a functional readout of microbial activity and can be used as an intermediate phenotype mediating host-microbiome interactions 3 . In this comprehensive description of the fecal metabolome, examining 1,116 metabolites from 786 individuals from a population-based twin study (TwinsUK), the fecal metabolome was found to be only modestly influenced by host genetics (heritability (H2) = 17.9%). One replicated locus at the NAT2 gene was associated with fecal metabolic traits. The fecal metabolome largely reflects gut microbial composition, explaining on average 67.7% (±18.8%) of its variance. It is strongly associated with visceral-fat mass, thereby illustrating potential mechanisms underlying the well-established microbial influence on abdominal obesity. Fecal metabolic profiling thus is a novel tool to explore links among microbiome composition, host phenotypes, and heritable complex traits.}, } @article {pmid29808029, year = {2018}, author = {Williams, MJ and Werner, B and Heide, T and Curtis, C and Barnes, CP and Sottoriva, A and Graham, TA}, title = {Quantification of subclonal selection in cancer from bulk sequencing data.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {895-903}, doi = {10.1038/s41588-018-0128-6}, pmid = {29808029}, issn = {1546-1718}, support = {R01 CA182514/CA/NCI NIH HHS/United States ; }, abstract = {Subclonal architectures are prevalent across cancer types. However, the temporal evolutionary dynamics that produce tumor subclones remain unknown. Here we measure clone dynamics in human cancers by using computational modeling of subclonal selection and theoretical population genetics applied to high-throughput sequencing data. Our method determined the detectable subclonal architecture of tumor samples and simultaneously measured the selective advantage and time of appearance of each subclone. We demonstrate the accuracy of our approach and the extent to which evolutionary dynamics are recorded in the genome. Application of our method to high-depth sequencing data from breast, gastric, blood, colon and lung cancer samples, as well as metastatic deposits, showed that detectable subclones under selection, when present, consistently emerged early during tumor growth and had a large fitness advantage (>20%). Our quantitative framework provides new insight into the evolutionary trajectories of human cancers and facilitates predictive measurements in individual tumors from widely available sequencing data.}, } @article {pmid29808028, year = {2018}, author = {Zhang, Y and Pitchiaya, S and Cieślik, M and Niknafs, YS and Tien, JC and Hosono, Y and Iyer, MK and Yazdani, S and Subramaniam, S and Shukla, SK and Jiang, X and Wang, L and Liu, TY and Uhl, M and Gawronski, AR and Qiao, Y and Xiao, L and Dhanasekaran, SM and Juckette, KM and Kunju, LP and Cao, X and Patel, U and Batish, M and Shukla, GC and Paulsen, MT and Ljungman, M and Jiang, H and Mehra, R and Backofen, R and Sahinalp, CS and Freier, SM and Watt, AT and Guo, S and Wei, JT and Feng, FY and Malik, R and Chinnaiyan, AM}, title = {Analysis of the androgen receptor-regulated lncRNA landscape identifies a role for ARLNC1 in prostate cancer progression.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {814-824}, pmid = {29808028}, issn = {1546-1718}, support = {DP5 OD012160/OD/NIH HHS/United States ; P50 CA186786/CA/NCI NIH HHS/United States ; T32 GM007315/GM/NIGMS NIH HHS/United States ; U01 CA214170/CA/NCI NIH HHS/United States ; }, abstract = {The androgen receptor (AR) plays a critical role in the development of the normal prostate as well as prostate cancer. Using an integrative transcriptomic analysis of prostate cancer cell lines and tissues, we identified ARLNC1 (AR-regulated long noncoding RNA 1) as an important long noncoding RNA that is strongly associated with AR signaling in prostate cancer progression. Not only was ARLNC1 induced by the AR protein, but ARLNC1 stabilized the AR transcript via RNA-RNA interaction. ARLNC1 knockdown suppressed AR expression, global AR signaling and prostate cancer growth in vitro and in vivo. Taken together, these data support a role for ARLNC1 in maintaining a positive feedback loop that potentiates AR signaling during prostate cancer progression and identify ARLNC1 as a novel therapeutic target.}, } @article {pmid29808027, year = {2018}, author = {Tedja, MS and Wojciechowski, R and Hysi, PG and Eriksson, N and Furlotte, NA and Verhoeven, VJM and Iglesias, AI and Meester-Smoor, MA and Tompson, SW and Fan, Q and Khawaja, AP and Cheng, CY and Höhn, R and Yamashiro, K and Wenocur, A and Grazal, C and Haller, T and Metspalu, A and Wedenoja, J and Jonas, JB and Wang, YX and Xie, J and Mitchell, P and Foster, PJ and Klein, BEK and Klein, R and Paterson, AD and Hosseini, SM and Shah, RL and Williams, C and Teo, YY and Tham, YC and Gupta, P and Zhao, W and Shi, Y and Saw, WY and Tai, ES and Sim, XL and Huffman, JE and Polašek, O and Hayward, C and Bencic, G and Rudan, I and Wilson, JF and , and , and , and Joshi, PK and Tsujikawa, A and Matsuda, F and Whisenhunt, KN and Zeller, T and van der Spek, PJ and Haak, R and Meijers-Heijboer, H and van Leeuwen, EM and Iyengar, SK and Lass, JH and Hofman, A and Rivadeneira, F and Uitterlinden, AG and Vingerling, JR and Lehtimäki, T and Raitakari, OT and Biino, G and Concas, MP and Schwantes-An, TH and Igo, RP and Cuellar-Partida, G and Martin, NG and Craig, JE and Gharahkhani, P and Williams, KM and Nag, A and Rahi, JS and Cumberland, PM and Delcourt, C and Bellenguez, C and Ried, JS and Bergen, AA and Meitinger, T and Gieger, C and Wong, TY and Hewitt, AW and Mackey, DA and Simpson, CL and Pfeiffer, N and Pärssinen, O and Baird, PN and Vitart, V and Amin, N and van Duijn, CM and Bailey-Wilson, JE and Young, TL and Saw, SM and Stambolian, D and MacGregor, S and Guggenheim, JA and Tung, JY and Hammond, CJ and Klaver, CCW}, title = {Genome-wide association meta-analysis highlights light-induced signaling as a driver for refractive error.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {834-848}, pmid = {29808027}, issn = {1546-1718}, support = {R21 EY027880/EY/NEI NIH HHS/United States ; R01 EY024233/EY/NEI NIH HHS/United States ; MC_UU_12015/1//Medical Research Council/United Kingdom ; R01 EY020483/EY/NEI NIH HHS/United States ; R01 EY014685/EY/NEI NIH HHS/United States ; }, abstract = {Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers.}, } @article {pmid29807997, year = {2018}, author = {Batterman, SA}, title = {Fixing tropical forests.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1059-1060}, doi = {10.1038/s41559-018-0583-6}, pmid = {29807997}, issn = {2397-334X}, } @article {pmid29807996, year = {2018}, author = {Jerlström Hultqvist, J and Warsi, O and Söderholm, A and Knopp, M and Eckhard, U and Vorontsov, E and Selmer, M and Andersson, DI}, title = {A bacteriophage enzyme induces bacterial metabolic perturbation that confers a novel promiscuous function.}, journal = {Nature ecology & evolution}, volume = {2}, number = {8}, pages = {1321-1330}, doi = {10.1038/s41559-018-0568-5}, pmid = {29807996}, issn = {2397-334X}, abstract = {One key concept in the evolution of new functions is the ability of enzymes to perform promiscuous side-reactions that serve as a source of novelty that may become beneficial under certain conditions. Here, we identify a mechanism where a bacteriophage-encoded enzyme introduces novelty by inducing expression of a promiscuous bacterial enzyme. By screening for bacteriophage DNA that rescued an auxotrophic Escherichia coli mutant carrying a deletion of the ilvA gene, we show that bacteriophage-encoded S-adenosylmethionine (SAM) hydrolases reduce SAM levels. Through this perturbation of bacterial metabolism, expression of the promiscuous bacterial enzyme MetB is increased, which in turn complements the absence of IlvA. These results demonstrate how foreign DNA can increase the metabolic capacity of bacteria, not only by transfer of bona fide new genes, but also by bringing cryptic bacterial functions to light via perturbations of cellular physiology.}, } @article {pmid29807995, year = {2018}, author = {Gei, M and Rozendaal, DMA and Poorter, L and Bongers, F and Sprent, JI and Garner, MD and Aide, TM and Andrade, JL and Balvanera, P and Becknell, JM and Brancalion, PHS and Cabral, GAL and César, RG and Chazdon, RL and Cole, RJ and Colletta, GD and de Jong, B and Denslow, JS and Dent, DH and DeWalt, SJ and Dupuy, JM and Durán, SM and do Espírito Santo, MM and Fernandes, GW and Nunes, YRF and Finegan, B and Moser, VG and Hall, JS and Hernández-Stefanoni, JL and Junqueira, AB and Kennard, D and Lebrija-Trejos, E and Letcher, SG and Lohbeck, M and Marín-Spiotta, E and Martínez-Ramos, M and Meave, JA and Menge, DNL and Mora, F and Muñoz, R and Muscarella, R and Ochoa-Gaona, S and Orihuela-Belmonte, E and Ostertag, R and Peña-Claros, M and Pérez-García, EA and Piotto, D and Reich, PB and Reyes-García, C and Rodríguez-Velázquez, J and Romero-Pérez, IE and Sanaphre-Villanueva, L and Sanchez-Azofeifa, A and Schwartz, NB and de Almeida, AS and Almeida-Cortez, JS and Silver, W and de Souza Moreno, V and Sullivan, BW and Swenson, NG and Uriarte, M and van Breugel, M and van der Wal, H and Veloso, MDDM and Vester, HFM and Vieira, ICG and Zimmerman, JK and Powers, JS}, title = {Legume abundance along successional and rainfall gradients in Neotropical forests.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1104-1111}, doi = {10.1038/s41559-018-0559-6}, pmid = {29807995}, issn = {2397-334X}, abstract = {The nutrient demands of regrowing tropical forests are partly satisfied by nitrogen-fixing legume trees, but our understanding of the abundance of those species is biased towards wet tropical regions. Here we show how the abundance of Leguminosae is affected by both recovery from disturbance and large-scale rainfall gradients through a synthesis of forest inventory plots from a network of 42 Neotropical forest chronosequences. During the first three decades of natural forest regeneration, legume basal area is twice as high in dry compared with wet secondary forests. The tremendous ecological success of legumes in recently disturbed, water-limited forests is likely to be related to both their reduced leaflet size and ability to fix N2, which together enhance legume drought tolerance and water-use efficiency. Earth system models should incorporate these large-scale successional and climatic patterns of legume dominance to provide more accurate estimates of the maximum potential for natural nitrogen fixation across tropical forests.}, } @article {pmid29807994, year = {2018}, author = {Cooper, GA and West, SA}, title = {Division of labour and the evolution of extreme specialization.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1161-1167}, doi = {10.1038/s41559-018-0564-9}, pmid = {29807994}, issn = {2397-334X}, abstract = {Division of labour is a common feature of social groups, from biofilms to complex animal societies. However, we lack a theoretical framework that can explain why division of labour has evolved on certain branches of the tree of life but not others. Here, we model the division of labour over a cooperative behaviour, considering both when it should evolve and the extent to which the different types should become specialized. We found that: (1) division of labour is usually-but not always-favoured by high efficiency benefits to specialization and low within-group conflict; and (2) natural selection favours extreme specialization, where some individuals are completely dependent on the helping behaviour of others. We make a number of predictions, several of which are supported by the existing empirical data, from microbes and animals, while others suggest novel directions for empirical work. More generally, we show how division of labour can lead to mutual dependence between different individuals and hence drive major evolutionary transitions, such as those to multicellularity and eusociality.}, } @article {pmid29807993, year = {2018}, author = {Gore, AV and Tomins, KA and Iben, J and Ma, L and Castranova, D and Davis, AE and Parkhurst, A and Jeffery, WR and Weinstein, BM}, title = {An epigenetic mechanism for cavefish eye degeneration.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1155-1160}, pmid = {29807993}, issn = {2397-334X}, support = {R01 EY024941/EY/NEI NIH HHS/United States ; ZIA HD001011-20/NULL/Intramural NIH HHS/United States ; }, abstract = {Coding and non-coding mutations in DNA contribute significantly to phenotypic variability during evolution. However, less is known about the role of epigenetics in this process. Although previous studies have identified eye development genes associated with the loss-of-eyes phenotype in the Pachón blind cave morph of the Mexican tetra Astyanax mexicanus, no inactivating mutations have been found in any of these genes. Here, we show that excess DNA methylation-based epigenetic silencing promotes eye degeneration in blind cave A. mexicanus. By performing parallel analyses in A. mexicanus cave and surface morphs, and in the zebrafish Danio rerio, we have discovered that DNA methylation mediates eye-specific gene repression and globally regulates early eye development. The most significantly hypermethylated and downregulated genes in the cave morph are also linked to human eye disorders, suggesting that the function of these genes is conserved across vertebrates. Our results show that changes in DNA methylation-based gene repression can serve as an important molecular mechanism generating phenotypic diversity during development and evolution.}, } @article {pmid29807992, year = {2018}, author = {Maidment, S}, title = {Theropods on top.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1049}, doi = {10.1038/s41559-018-0571-x}, pmid = {29807992}, issn = {2397-334X}, } @article {pmid29807988, year = {2018}, author = {Sieber, CMK and Probst, AJ and Sharrar, A and Thomas, BC and Hess, M and Tringe, SG and Banfield, JF}, title = {Recovery of genomes from metagenomes via a dereplication, aggregation and scoring strategy.}, journal = {Nature microbiology}, volume = {3}, number = {7}, pages = {836-843}, doi = {10.1038/s41564-018-0171-1}, pmid = {29807988}, issn = {2058-5276}, abstract = {Microbial communities are critical to ecosystem function. A key objective of metagenomic studies is to analyse organism-specific metabolic pathways and reconstruct community interaction networks. This requires accurate assignment of assembled genome fragments to genomes. Existing binning methods often fail to reconstruct a reasonable number of genomes and report many bins of low quality and completeness. Furthermore, the performance of existing algorithms varies between samples and biotopes. Here, we present a dereplication, aggregation and scoring strategy, DAS Tool, that combines the strengths of a flexible set of established binning algorithms. DAS Tool applied to a constructed community generated more accurate bins than any automated method. Indeed, when applied to environmental and host-associated samples of different complexity, DAS Tool recovered substantially more near-complete genomes, including previously unreported lineages, than any single binning method alone. The ability to reconstruct many near-complete genomes from metagenomics data will greatly advance genome-centric analyses of ecosystems.}, } @article {pmid29807840, year = {2018}, author = {Nordén, KK and Price, TD}, title = {Historical Contingency and Developmental Constraints in Avian Coloration.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {574-576}, doi = {10.1016/j.tree.2018.05.003}, pmid = {29807840}, issn = {1872-8383}, abstract = {The remarkable diversity of color in nature remains largely unexplained. Recent studies on birds show how historical reconstructions, the identification of genes affecting color differences, and an increased understanding of the underlying developmental mechanisms are helping to explain why species are the color they are.}, } @article {pmid29807839, year = {2018}, author = {Mori, AS and Isbell, F and Seidl, R}, title = {β-Diversity, Community Assembly, and Ecosystem Functioning.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {549-564}, doi = {10.1016/j.tree.2018.04.012}, pmid = {29807839}, issn = {1872-8383}, abstract = {Evidence is increasing for positive effects of α-diversity on ecosystem functioning. We highlight here the crucial role of β-diversity - a hitherto underexplored facet of biodiversity - for a better process-level understanding of biodiversity change and its consequences for ecosystems. A focus on β-diversity has the potential to improve predictions of natural and anthropogenic influences on diversity and ecosystem functioning. However, linking the causes and consequences of biodiversity change is complex because species assemblages in nature are shaped by many factors simultaneously, including disturbance, environmental heterogeneity, deterministic niche factors, and stochasticity. Because variability and change are ubiquitous in ecosystems, acknowledging these inherent properties of nature is an essential step for further advancing scientific knowledge of biodiversity-ecosystem functioning in theory and practice.}, } @article {pmid29807838, year = {2018}, author = {Buck, JC and Weinstein, SB and Young, HS}, title = {Ecological and Evolutionary Consequences of Parasite Avoidance.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {8}, pages = {619-632}, doi = {10.1016/j.tree.2018.05.001}, pmid = {29807838}, issn = {1872-8383}, abstract = {Predators often cause prey to adopt defensive strategies that reduce predation risk. The 'ecology of fear' examines these trait changes and their consequences. Similarly, parasites can cause hosts to adopt defensive strategies that reduce infection risk. However the ecological and evolutionary consequences of these behaviors (the 'ecology of disgust') are seldom considered. Here we identify direct and indirect effects of parasite avoidance on hosts and parasites, and examine differences between predators and parasites in terms of cost, detectability, and aggregation. We suggest that the nonconsumptive effects of parasites might overshadow their consumptive effects, as has been shown for predators. We emphasize the value of uniting predator-prey and parasite-host theory under a general consumer-resource framework.}, } @article {pmid29807759, year = {2018}, author = {Nötzel, C and Poran, A and Kafsack, BFC}, title = {Single-Cell Transcriptome Profiling of Protozoan and Metazoan Parasites.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {731-734}, doi = {10.1016/j.pt.2018.04.009}, pmid = {29807759}, issn = {1471-5007}, abstract = {Single-cell RNA sequencing (scRNAseq) technologies are changing the way we study populations of cells by allowing for an unbiased characterization of the composition of these populations. This Forum article highlights outstanding questions in parasitology that could benefit from scRNAseq and provides guiding thoughts for planning such experiments.}, } @article {pmid29807758, year = {2018}, author = {Leitsch, D and Williams, CF and Hrdý, I}, title = {Redox Pathways as Drug Targets in Microaerophilic Parasites.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {576-589}, doi = {10.1016/j.pt.2018.04.007}, pmid = {29807758}, issn = {1471-5007}, mesh = {Animals ; Drug Delivery Systems/*trends ; Entamoeba histolytica/drug effects/physiology ; Giardia lamblia/drug effects/physiology ; Humans ; *Oxidation-Reduction ; Oxygen/pharmacology ; Parasites/drug effects/*enzymology ; Trichomonas vaginalis/drug effects/physiology ; }, abstract = {The microaerophilic parasites Entamoeba histolytica, Trichomonas vaginalis, and Giardia lamblia jointly cause hundreds of millions of infections in humans every year. Other microaerophilic parasites such as Tritrichomonas foetus and Spironucleus spp. pose a relevant health problem in veterinary medicine. Unfortunately, vaccines against these pathogens are unavailable, but their microaerophilic lifestyle opens opportunities for specifically developed chemotherapeutics. In particular, their high sensitivity towards oxygen can be exploited by targeting redox enzymes. This review focusses on the redox pathways of microaerophilic parasites and on drugs, either already in use or currently in the state of development, which target these pathways.}, } @article {pmid29807746, year = {2018}, author = {Elserafy, M and Abugable, AA and Atteya, R and El-Khamisy, SF}, title = {Rad5, HLTF, and SHPRH: A Fresh View of an Old Story.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {574-577}, pmid = {29807746}, issn = {0168-9525}, abstract = {Not only have helicase-like transcription factor (HLTF) and SNF2 histone-linker PHD-finger RING-finger helicase (SHPRH) proved to be important players in post-replication repair like their yeast counterpart, Rad5, but they are also involved in multiple biological functions and are associated with several human disorders. We provide here an updated view of their functions, associated diseases, and potential therapeutic approaches.}, } @article {pmid29807655, year = {2018}, author = {Wood, CR and Mack, LE and Actis, LA}, title = {An Update on the Acinetobacter baumannii Regulatory Circuitry.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {560-562}, pmid = {29807655}, issn = {1878-4380}, support = {R15 GM117478/GM/NIGMS NIH HHS/United States ; }, abstract = {Acinetobacter baumannii adapts to different environmental conditions by expressing complex regulatory circuitry. Recent studies revealed that this circuitry includes regulatory factors that control the emergence of distinct bacterial subpopulations, which are critical for the capacity of this pathogen to persist in medical settings and cause infections in compromised hosts.}, } @article {pmid29807156, year = {2018}, author = {Eldridge, MDB and Potter, S and Helgen, KM and Sinaga, MH and Aplin, KP and Flannery, TF and Johnson, RN}, title = {Phylogenetic analysis of the tree-kangaroos (Dendrolagus) reveals multiple divergent lineages within New Guinea.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {589-599}, doi = {10.1016/j.ympev.2018.05.030}, pmid = {29807156}, issn = {1095-9513}, mesh = {Animals ; Biodiversity ; Biological Evolution ; Macropodidae/*classification/genetics ; New Guinea ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Amongst the Australasian kangaroos and wallabies (Macropodidae) one anomalous genus, the tree-kangaroos, Dendrolagus, has secondarily returned to arboreality. Modern tree-kangaroos are confined to the wet tropical forests of north Queensland, Australia (2 species) and New Guinea (8 species). Due to their behavior, distribution and habitat most species are poorly known and our understanding of the evolutionary history and systematics of the genus is limited and controversial. We obtained tissue samples from 36 individual Dendrolagus including representatives from 14 of the 17 currently recognised or proposed subspecies and generated DNA sequence data from three mitochondrial (3116 bp) and five nuclear (4097 bp) loci. Phylogenetic analysis of these multi-locus data resolved long-standing questions regarding inter-relationships within Dendrolagus. The presence of a paraphyletic ancestral long-footed and derived monophyletic short-footed group was confirmed. Six major lineages were identified: one in Australia (D. lumholtzi, D. bennettianus) and five in New Guinea (D. inustus, D. ursinus, a Goodfellow's group, D. mbaiso and a Doria's group). Two major episodes of diversification within Dendrolagus were identified: the first during the late Miocene/early Pliocene associated with orogenic processes in New Guinea and the second mostly during the early Pleistocene associated with the intensification of climatic cycling. All sampled subspecies showed high levels of genetic divergence and currently recognized species within both the Doria's and Goodfellow's groups were paraphyletic indicating that adjustments to current taxonomy are warranted.}, } @article {pmid29807155, year = {2018}, author = {Munds, RA and Titus, CL and Eggert, LS and Blomquist, GE}, title = {Using a multi-gene approach to infer the complicated phylogeny and evolutionary history of lorises (Order Primates: Family Lorisidae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {556-567}, doi = {10.1016/j.ympev.2018.05.025}, pmid = {29807155}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Biological Evolution ; Cell Nucleus/genetics ; Genes, Mitochondrial ; Lorisidae/*classification/genetics ; *Phylogeny ; }, abstract = {Extensive phylogenetic studies have found robust phylogenies are modeled by using a multi-gene approach and sampling from the majority of the taxa of interest. Yet, molecular studies focused on the lorises, a cryptic primate family, have often relied on one gene, or just mitochondrial DNA, and many were unable to include all four genera in the analyses, resulting in inconclusive phylogenies. Past phylogenetic loris studies resulted in lorises being monophyletic, paraphyletic, or an unresolvable trichotomy with the closely related galagos. The purpose of our study is to improve our understanding of loris phylogeny and evolutionary history by using a multi-gene approach. We used the mitochondrial genes cytochrome b, and cytochrome c oxidase subunit 1, along with a nuclear intron (recombination activating gene 2) and nuclear exon (the melanocortin 1 receptor). Maximum Likelihood and Bayesian phylogenetic analyses were conducted based on data from each locus, as well as on the concatenated sequences. The robust, concatenated results found lorises to be a monophyletic family (Lorisidae) (PP ≥ 0.99) with two distinct subfamilies: the African Perodictinae (PP ≥ 0.99) and the Asian Lorisinae (PP ≥ 0.99). Additionally, from these analyses all four genera were all recovered as monophyletic (PP ≥ 0.99). Some of our single-gene analyses recovered monophyly, but many had discordances, with some showing paraphyly or a deep-trichotomy. Bayesian partitioned analyses inferred the most recent common ancestors of lorises emerged ∼42 ± 6 million years ago (mya), the Asian Lorisinae separated ∼30 ± 9 mya, and Perodictinae arose ∼26 ± 10 mya. These times fit well with known historical tectonic shifts of the area, as well as with the sparse loris fossil record. Additionally, our results agree with previous multi-gene studies on Lorisidae which found lorises to be monophyletic and arising ∼40 mya (Perelman et al., 2011; Pozzi et al., 2014). By taking a multi-gene approach, we were able to recover a well-supported, monophyletic loris phylogeny and inferred the evolutionary history of this cryptic family.}, } @article {pmid29807154, year = {2018}, author = {Suzuki, T and Inoue, Y and Tsubota, H}, title = {Molecular phylogeny of the genus Fissidens (Fissidentaceae, Bryophyta) and a refinement of the infrageneric classification.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {190-202}, doi = {10.1016/j.ympev.2018.05.020}, pmid = {29807154}, issn = {1095-9513}, abstract = {The genus Fissidens (ca. 440 spp.) is one of the phylogenetically poorly studied groups of mosses (Bryophyta). While various classifications of this genus have been proposed, no attempt at a classification of the genus based on combined molecular and morphological evidence has been made. Here, we present for the first time a comprehensive phylogenetic tree consisting of 50 representatives of Fissidens, reconstructed using sequence data from chloroplast rbcL and rps4 genes. Ancestral state reconstructions provide three clear apomorphies within Fissidens: peristome teeth, limbidium and chromosome number. Based on the phylogeny and morphological reassessment, we recognize three subgenera, Pachyfissidens, Neoamblyothallia, and Fissidens. Subgenus Neoamblyothallia consists of two sections: Neoamblyothallia and Crispidium. Subgenus Fissidens consists of five sections: Fissidens, Polypodiopsis, Aloma, Areofissidens, and Semilimbidium. High diversity of the most derived sect. Semilimbidium in the tropics suggests that the evolutionary history of the genus is through adaptation and diversification in tropical regions.}, } @article {pmid29807096, year = {2018}, author = {Zwama, M and Yamaguchi, A}, title = {Molecular mechanisms of AcrB-mediated multidrug export.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {372-383}, doi = {10.1016/j.resmic.2018.05.005}, pmid = {29807096}, issn = {1769-7123}, mesh = {Animals ; Anti-Bacterial Agents/*metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biological Transport ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria/chemistry/classification/genetics/*metabolism ; Gram-Negative Bacterial Infections/microbiology ; Humans ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; }, abstract = {The over-expression of multidrug efflux pumps belonging to the Resistance-Nodulation-Division (RND) superfamily is one of the main causes of multidrug-resistance (MDR) in Gram-negative pathogenic bacteria. AcrB is the most thoroughly studied RND transporter and has functioned as a model for our understanding of efflux-mediated MDR. This multidrug-exporter can recognize and transport a wide range of structurally unrelated compounds (including antibiotics, dyes, bile salts and detergents), while it shows a strict inhibitor specificity. Here we discuss our current knowledge of AcrB, and include recent advances, regarding its structure, mechanism of drug transport, substrate recognition, different intramolecular entry pathways and the drug export driven by remote conformational coupling.}, } @article {pmid29807017, year = {2018}, author = {Hockman, D and Adameyko, I and Kaucka, M and Barraud, P and Otani, T and Hunt, A and Hartwig, AC and Sock, E and Waithe, D and Franck, MCM and Ernfors, P and Ehinger, S and Howard, MJ and Brown, N and Reese, J and Baker, CVH}, title = {Striking parallels between carotid body glomus cell and adrenal chromaffin cell development.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.05.016}, pmid = {29807017}, issn = {1095-564X}, abstract = {Carotid body glomus cells mediate essential reflex responses to arterial blood hypoxia. They are dopaminergic and secrete growth factors that support dopaminergic neurons, making the carotid body a potential source of patient-specific cells for Parkinson's disease therapy. Like adrenal chromaffin cells, which are also hypoxia-sensitive, glomus cells are neural crest-derived and require the transcription factors Ascl1 and Phox2b; otherwise, their development is little understood at the molecular level. Here, analysis in chicken and mouse reveals further striking molecular parallels, though also some differences, between glomus and adrenal chromaffin cell development. Moreover, histology has long suggested that glomus cell precursors are 'émigrés' from neighbouring ganglia/nerves, while multipotent nerve-associated glial cells are now known to make a significant contribution to the adrenal chromaffin cell population in the mouse. We present conditional genetic lineage-tracing data from mice supporting the hypothesis that progenitors expressing the glial marker proteolipid protein 1, presumably located in adjacent ganglia/nerves, also contribute to glomus cells. Finally, we resolve a paradox for the 'émigré' hypothesis in the chicken - where the nearest ganglion to the carotid body is the nodose, in which the satellite glia are neural crest-derived, but the neurons are almost entirely placode-derived - by fate-mapping putative nodose neuronal 'émigrés' to the neural crest.}, } @article {pmid29806735, year = {2018}, author = {Abreu, F and Leão, P and Vargas, G and Cypriano, J and Figueiredo, V and Enrich-Prast, A and Bazylinski, DA and Lins, U}, title = {Culture-independent characterization of a novel magnetotactic member affiliated to the Beta class of the Proteobacteria phylum from an acidic lagoon.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2615-2624}, doi = {10.1111/1462-2920.14286}, pmid = {29806735}, issn = {1462-2920}, abstract = {Magnetotactic bacteria (MTB) comprise a group of motile microorganisms common in most mesothermal aquatic habitats with pH values around neutrality. However, during the last two decades, a number of MTB from extreme environments have been characterized including: cultured alkaliphilic strains belonging to the Deltaproteobacteria class of the Proteobacteria phylum; uncultured moderately thermophilic strains belonging to the Nitrospirae phylum; cultured and uncultured moderately halophilic or strongly halotolerant bacteria affiliated with the Deltaproteobacteria and Gammaproteobacteria classes and an uncultured psychrophilic species belonging to the Alphaproteobacteria class. Here, we used culture-independent techniques to characterize MTB from an acidic freshwater lagoon in Brazil (pH ∼ 4.4). MTB morphotypes found in this acidic lagoon included cocci, rods, spirilla and vibrioid cells. Magnetite (Fe3 O4) was the only mineral identified in magnetosomes of these MTB while magnetite magnetosome crystal morphologies within the different MTB cells included cuboctahedral (present in spirilla), elongated prismatic (present in cocci and vibrios) and bullet-shaped (present in rod-shaped cells). Intracellular pH measurements using fluorescent dyes showed that the cytoplasmic pH was close to neutral in most MTB cells and acidic in some intracellular granules. Based on 16S rRNA gene phylogenetic analyses, some of the retrieved gene sequences belonged to the genus Herbaspirillum within the Betaproteobacteria class of the Proteobacteria phylum. Fluorescent in situ hybridization using a Herbaspirillum-specific probe hybridized with vibrioid MTB in magnetically-enriched samples. Transmission electron microscopy of the Herbaspirillum-like MTB revealed the presence of many intracellular granules and a single chain of elongated prismatic magnetite magnetosomes. Diverse populations of MTB have not seemed to have been described in detail in an acid environment. In addition, this is the first report of an MTB phylogenetically affiliated with Betaproteobacteria class.}, } @article {pmid29806731, year = {2018}, author = {Kasahara, M and Kobayashi, C and Sakaguchi, C and Miyahara, C and Yamanaka, A and Kitazawa, C}, title = {Effects of Nodal inhibition on development of temnopleurid sea urchins.}, journal = {Evolution & development}, volume = {20}, number = {3-4}, pages = {91-99}, doi = {10.1111/ede.12254}, pmid = {29806731}, issn = {1525-142X}, mesh = {Animals ; Benzamides/pharmacology ; Body Patterning ; Dioxoles/pharmacology ; Gene Expression Regulation, Developmental ; Nodal Protein/antagonists & inhibitors/*metabolism ; Sea Urchins/classification/genetics/*growth & development ; }, abstract = {Adult rudiment formation in some temnopleurids begins with the formation of a cell mass that is pinched off the left ectoderm in early larval development. The cell mass forms the adult rudiment with the left coelomic pouch of the mesodermal region. However, details of the mechanisms to establish position of the cell mass are still unknown. We analyzed the inhibiting effect of Nodal, a factor for morphogenesis of the oral region and right side, for location of the cell mass, in four temnopleurids. Pulse inhibition, at least 5 min inhibition, during coelomic pouch formation allowed a cell mass to form on both sides, whereas treatments after that period did not. These results indicate that Nodal signaling controls the oral-aboral axis before gastrulation and then affects the position of the cell mass and adult rudiment up to coelomic pouch formation. They also indicate that the position of the adult rudiment under Nodal signaling pathways is conserved in temnopleurids, as adult rudiment formation is dependent on the cell mass.}, } @article {pmid29806730, year = {2018}, author = {Graf, JS and Mayr, MJ and Marchant, HK and Tienken, D and Hach, PF and Brand, A and Schubert, CJ and Kuypers, MMM and Milucka, J}, title = {Bloom of a denitrifying methanotroph, 'Candidatus Methylomirabilis limnetica', in a deep stratified lake.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2598-2614}, doi = {10.1111/1462-2920.14285}, pmid = {29806730}, issn = {1462-2920}, abstract = {Methanotrophic bacteria represent an important biological filter regulating methane emissions into the atmosphere. Planktonic methanotrophic communities in freshwater lakes are typically dominated by aerobic gamma-proteobacteria, with a contribution from alpha-proteobacterial methanotrophs and the NC10 bacteria. The NC10 clade encompasses methanotrophs related to 'Candidatus Methylomirabilis oxyfera', which oxidize methane using a unique pathway of denitrification that tentatively produces N2 and O2 from nitric oxide (NO). Here, we describe a new species of the NC10 clade, 'Ca. Methylomirabilis limnetica', which dominated the planktonic microbial community in the anoxic depths of the deep stratified Lake Zug in two consecutive years, comprising up to 27% of the total bacterial population. Gene transcripts assigned to 'Ca. M. limnetica' constituted up to one third of all metatranscriptomic sequences in situ. The reconstructed genome encoded a complete pathway for methane oxidation, and an incomplete denitrification pathway, including two putative nitric oxide dismutase genes. The genome of 'Ca. M. limnetica' exhibited features possibly related to genome streamlining (i.e. less redundancy of key metabolic genes) and adaptation to its planktonic habitat (i.e. gas vesicle genes). We speculate that 'Ca. M. limnetica' temporarily bloomed in the lake during non-steady-state conditions suggesting a niche for NC10 bacteria in the lacustrine methane and nitrogen cycle.}, } @article {pmid29806725, year = {2018}, author = {Gong, Y and Zhang, Z and Liu, Y and Zhou, XW and Anwar, MN and Li, ZS and Hu, W and Li, YZ}, title = {A nuclease-toxin and immunity system for kin discrimination in Myxococcus xanthus.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2552-2567}, doi = {10.1111/1462-2920.14282}, pmid = {29806725}, issn = {1462-2920}, abstract = {The use of toxin to attack neighbours and immunity proteins to protect against toxin has been observed in bacterial conflicts, including kin discrimination. Here, we report a novel nuclease-toxin and its immunity protein function in the colony-merger incompatibility, a kind of bacterial kin discrimination, in Myxococcus xanthus DK1622. The MXAN_0049 gene was determined to be a genetic determinant for colony-merger incompatibility, and the incompatibility could be eliminated by deletion of the upstream co-transcribed MXAN_0050 gene. We demonstrated that the MXAN_0050 protein was a nuclease, and MXAN_0049 protein was able to bind to MXAN_0050 to block nuclease activity in vitro. Expression of MXAN_0050 in Escherichia coli inhibited cellular growth, and the inhibition effect could be recovered by co-expression of MXAN_0049. We found that deletion of the PAAR-encoding gene (MXAN_0044) or the type VI secretion system led to the colony-merger and co-existence with the ΔMXAN_0049 mutant, suggesting that they were associated with colony-merger incompatibility. Homologues of the nuclease-toxin and cognate immunity pair are widely distributed in bacteria. We propose a simplified model to explain the kin discrimination mechanism mediated by the nuclease-toxin and immunity protein.© 2018 Society for Applied Microbiology and John Wiley & Sons Ltd.}, } @article {pmid29806719, year = {2018}, author = {Guan, Y and Tsao, CY and Quan, DN and Li, Y and Mei, L and Song, Y and Zhang, B and Liu, Y and Payne, GF and Bentley, WE and Wang, Q}, title = {Focusing quorum sensing signalling by nano-magnetic assembly.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2585-2597}, pmid = {29806719}, issn = {1462-2920}, support = {R21 EB024102/EB/NIBIB NIH HHS/United States ; }, abstract = {Quorum sensing (QS) exists widely among bacteria, enabling a transition to multicellular behaviour after bacterial populations reach a particular density. The coordination of multicellularity enables biotechnological application, dissolution of biofilms, coordination of virulence, and so forth. Here, a method to elicit and subsequently disperse multicellular behaviour among QS-negative cells is developed using magnetic nanoparticle assembly. We fabricated magnetic nanoparticles (MNPs, ∼5 nm) that electrostatically collect wild-type (WT) Escherichia coli BL21 cells and brings them into proximity of bioengineered E. coli [CT104 (W3110 lsrFG- luxS- pCT6 + pET-DsRed)] reporter cells that exhibit a QS response after receiving autoinducer-2 (AI-2). By shortening the distance between WT and reporter cells (e.g., increasing local available AI-2 concentrations), the QS response signalling was amplified four-fold compared to that in native conditions without assembly. This study suggests potential applications in facilitating intercellular communication and modulating multicellular behaviours based on user-specified designs.}, } @article {pmid29806691, year = {2018}, author = {Mazzaferri, F and Cordioli, M and Segato, E and Adami, I and Maccacaro, L and Sette, P and Cazzadori, A and Concia, E and Azzini, AM}, title = {Nocardia infection over 5 years (2011-2015) in an Italian tertiary care hospital.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {136-140}, pmid = {29806691}, issn = {1121-7138}, mesh = {Aged ; Aged, 80 and over ; Anti-Bacterial Agents/pharmacology/therapeutic use ; Drug Resistance, Bacterial ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Nocardia/drug effects/*isolation & purification ; Nocardia Infections/drug therapy/*epidemiology/*microbiology ; Retrospective Studies ; Tertiary Care Centers ; }, abstract = {This study was conducted reviewing clinical records of 14 patients affected by nocardiosis over 5 years in a tertiary care hospital. Nocardia abscessus was responsible for one third of infections, deviating significantly from the results reported by other epidemiological investigations and highlighting the key role of molecular identification tests. Indeed, a precise identification of species is crucial for the determination of antibiotic sensitivity patterns and, consequently, for the choice of antibiotic treatment. Noteworthy, 40% of isolates of N. abscessus (formerly N. asteroides complex) showed resistance to carbapenems, which are usually recommended for empirical therapy.}, } @article {pmid29806690, year = {2018}, author = {Borderi, M and Angarano, G and Antinori, A and Chirianni, A and Cinque, P and D'Arminio Monforte, A and Di Biagio, A and Di Perri, G and Galli, M and Gori, A and Lazzarin, A and Mussini, C and Perno, CF and Quirino, T and Rizzardini, G and Calza, L and Viale, P and Acone, B and Andreoni, M}, title = {Managing the long surviving HIV patient: a proposal for a multidimensional first-level diagnostic assessment.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {112-117}, pmid = {29806690}, issn = {1121-7138}, mesh = {Algorithms ; Anti-HIV Agents/administration & dosage/*therapeutic use ; Comorbidity ; Delphi Technique ; HIV Infections/*diagnosis/*drug therapy ; Humans ; Longevity ; Quality of Life ; }, abstract = {We propose a multidimensional first-level diagnostic assessment easy to use in routine clinical practice to allow infectious disease specialists to have a general and complete overview of persons living with HIV. Following the Delphi method, articles published from January 1, 2011 on controlled trials, clinical reports and observational studies dealing specifically with HIV and its co-morbidities were selected for review by the authors. Participants in the poll were selected among clinicians and infectious diseases specialists, working in 38 different dedicated HIV centres in Italy. The participants were given access to a website dedicated to the project and received a standardized information package containing a synopsis of the study and a description of the Delphi process and the selected literature. A total of 131 Items were divided into 10 first-level survey areas: anamnesis, objective examination, infectious diseases, osteoporosis diagnosis, metabolic pathologies diagnosis, cardiovascular diagnosis, nephrologic diagnosis, hepatological diagnosis, central nervous system diagnosis, evaluation of quality of life (QoL). This simple and concise first level tool identifies a few areas of multi-organ diagnostic assessment beyond the infectivity area. The identification of these areas will allow us to find shared and validated evaluation procedures with the intent to increase the likelihood of early recognition of patients at risk of comorbidity development, in order to facilitate more effective prevention, thereby reducing the overall impact on the quality of life of patients affected by this chronic illness.}, } @article {pmid29806172, year = {2018}, author = {Sciuchetti, L and Dufresnes, C and Cavoto, E and Brelsford, A and Perrin, N}, title = {Dobzhansky-Muller incompatibilities, dominance drive, and sex-chromosome introgression at secondary contact zones: A simulation study.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13510}, pmid = {29806172}, issn = {1558-5646}, abstract = {Dobzhansky-Muller (DM) incompatibilities involving sex chromosomes have been proposed to account for Haldane's rule (lowered fitness among hybrid offspring of the heterogametic sex) as well as Darwin's corollary (asymmetric fitness costs with respect to the direction of the cross). We performed simulation studies of a hybrid zone to investigate the effects of different types of DM incompatibilities on cline widths and positions of sex-linked markers. From our simulations, X-Y incompatibilities generate steep clines for both X-linked and Y-linked markers; random effects may produce strong noise in cline center positions when migration is high relative to fitness costs, but X- and Y-centers always coincide strictly. X-autosome and Y-autosome incompatibilities also generate steep clines, but systematic shifts in cline centers occur when migration is high relative to selection, as a result of a dominance drive linked to Darwin's corollary. Interestingly, sex-linked genes always show farther introgression than the associated autosomal genes. We discuss ways of disentangling the potentially confounding effects of sex biases in migration, we compare our results to those of a few documented contact zones, and we stress the need to study independent replicates of the same contact zone.}, } @article {pmid29806154, year = {2018}, author = {Hvala, JA and Frayer, ME and Payseur, BA}, title = {Signatures of hybridization and speciation in genomic patterns of ancestry.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, pmid = {29806154}, issn = {1558-5646}, support = {R01 GM120051/GM/NIGMS NIH HHS/United States ; T32 GM007133/GM/NIGMS NIH HHS/United States ; }, abstract = {Genomes sampled from hybrid zones between nascent species provide important clues into the speciation process. With advances in genome sequencing and single nucleotide polymorphism (SNP) genotyping, it is now feasible to measure variation in gene flow with high genomic resolution. This progress motivates the development of conceptual and analytical frameworks for hybrid zones that complement well-established cline approaches. We extend the perspective that genomic distributions of ancestry are sensitive indicators of hybridization history. We use simulations to examine the behavior of the number of ancestry junctions-a simple summary of genomic patterns-in hybrid zones under increasingly realistic scenarios. Neutral simulations revealed that ancestry junction number is shaped by population structure, migration rate, and population size. Modeling multiple genetic architectures of hybrid dysfunction, with an emphasis on epistatic hybrid incompatibilities, showed that selection reduces junction number near loci that confer reproductive barriers. The magnitude of this signature was affected by the form of selection, dominance, and genomic location (autosome vs. sex chromosome) of incompatible loci. Our results suggest that researchers can identify loci involved in reproductive isolation by scanning hybrid genomes for local reductions in junction number. We outline necessary directions for future theory and method development to realize this goal.}, } @article {pmid29805175, year = {2018}, author = {Wong, K and Gehring, K}, title = {Deciphering the catalytic mechanism of bacterial ubiquitination.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {644-645}, doi = {10.1038/d41586-018-05250-6}, pmid = {29805175}, issn = {1476-4687}, mesh = {Catalysis ; Catalytic Domain ; *Protein Processing, Post-Translational ; *Ubiquitination ; }, } @article {pmid29805174, year = {2018}, author = {Luis, F and Coronado, E}, title = {Spinning on the edge of graphene.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {645-647}, doi = {10.1038/d41586-018-05240-8}, pmid = {29805174}, issn = {1476-4687}, } @article {pmid29805172, year = {2018}, author = {Gatti, F}, title = {Molecular dynamics simulated by photons.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {641-642}, doi = {10.1038/d41586-018-05245-3}, pmid = {29805172}, issn = {1476-4687}, mesh = {*Molecular Dynamics Simulation ; Optics and Photonics ; *Photons ; Physics ; }, } @article {pmid29805168, year = {2018}, author = {}, title = {Tracing Zika's uncharted spread.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {614}, doi = {10.1038/d41586-018-05274-y}, pmid = {29805168}, issn = {1476-4687}, } @article {pmid29805167, year = {2018}, author = {}, title = {'Thank you' has little currency worldwide.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {615}, doi = {10.1038/d41586-018-05258-y}, pmid = {29805167}, issn = {1476-4687}, } @article {pmid29805166, year = {2018}, author = {}, title = {Streams may skew carbon cycle as climate warms.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {615}, doi = {10.1038/d41586-018-05239-1}, pmid = {29805166}, issn = {1476-4687}, } @article {pmid29805165, year = {2018}, author = {}, title = {The Galaxy's full glory revealed.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {615}, doi = {10.1038/d41586-018-05229-3}, pmid = {29805165}, issn = {1476-4687}, } @article {pmid29805164, year = {2018}, author = {}, title = {Sticky tape on historic artworks comes clean.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {614-615}, doi = {10.1038/d41586-018-05238-2}, pmid = {29805164}, issn = {1476-4687}, } @article {pmid29805163, year = {2018}, author = {}, title = {The brain waves that make frogs pitch perfect.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {615}, doi = {10.1038/d41586-018-05237-3}, pmid = {29805163}, issn = {1476-4687}, } @article {pmid29805162, year = {2018}, author = {Foo, JL and Chang, MW}, title = {Synthetic yeast genome reveals its versatility.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {647-648}, doi = {10.1038/d41586-018-05164-3}, pmid = {29805162}, issn = {1476-4687}, mesh = {Genetic Engineering ; Saccharomyces cerevisiae/*genetics ; *Synthetic Biology ; }, } @article {pmid29805161, year = {2018}, author = {}, title = {The giant rock that wiped out tree-dwelling birds.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {615}, doi = {10.1038/d41586-018-05228-4}, pmid = {29805161}, issn = {1476-4687}, } @article {pmid29805160, year = {2018}, author = {}, title = {Ants' route-finding abilities put mapping software to shame.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {614}, doi = {10.1038/d41586-018-05227-5}, pmid = {29805160}, issn = {1476-4687}, } @article {pmid29805159, year = {2018}, author = {}, title = {A liquid crystal that could make your television screen brighter and clearer.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {614}, doi = {10.1038/d41586-018-05224-8}, pmid = {29805159}, issn = {1476-4687}, } @article {pmid29805158, year = {2018}, author = {Jensen, KN and Lorincz, MC}, title = {HP1 proteins safeguard embryonic stem cells.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {640-641}, doi = {10.1038/d41586-018-05188-9}, pmid = {29805158}, issn = {1476-4687}, mesh = {Amino Acid Sequence ; Chromosomal Proteins, Non-Histone/*genetics ; *Embryonic Stem Cells ; Heterochromatin ; }, } @article {pmid29805157, year = {2018}, author = {Wekerle, H}, title = {Brain inflammatory cascade controlled by gut-derived molecules.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {642-643}, doi = {10.1038/d41586-018-05113-0}, pmid = {29805157}, issn = {1476-4687}, mesh = {*Brain ; *Gastrointestinal Tract ; *Inflammation ; }, } @article {pmid29804937, year = {2018}, author = {Chapron, G and Levrel, H and Meinard, Y and Courchamp, F}, title = {Satire for Conservation in the 21st Century.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {478-480}, doi = {10.1016/j.tree.2018.04.017}, pmid = {29804937}, issn = {1872-8383}, } @article {pmid29804936, year = {2018}, author = {Melián, CJ and Matthews, B and de Andreazzi, CS and Rodríguez, JP and Harmon, LJ and Fortuna, MA}, title = {Deciphering the Interdependence between Ecological and Evolutionary Networks.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {504-512}, doi = {10.1016/j.tree.2018.04.009}, pmid = {29804936}, issn = {1872-8383}, abstract = {Biological systems consist of elements that interact within and across hierarchical levels. For example, interactions among genes determine traits of individuals, competitive and cooperative interactions among individuals influence population dynamics, and interactions among species affect the dynamics of communities and ecosystem processes. Such systems can be represented as hierarchical networks, but can have complex dynamics when interdependencies among levels of the hierarchy occur. We propose integrating ecological and evolutionary processes in hierarchical networks to explore interdependencies in biological systems. We connect gene networks underlying predator-prey trait distributions to food webs. Our approach addresses longstanding questions about how complex traits and intraspecific trait variation affect the interdependencies among biological levels and the stability of meta-ecosystems.}, } @article {pmid29804746, year = {2018}, author = {Morales, ME and Kaul, T and Deininger, P}, title = {Long-Distance Relationships: Suppression of Repeat-Mediated Deletions.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {8}, pages = {572-574}, pmid = {29804746}, issn = {0168-9525}, support = {R01 GM121812/GM/NIGMS NIH HHS/United States ; }, abstract = {The high proportion of repetitive DNA sequences in the human genome provides tremendous opportunities for DNA rearrangements between non-allelic repetitive elements. The genome must use multiple competing and collaborating repair mechanisms to minimize these types of DNA rearrangements, some of which fail in cancer cells where DNA repair pathways are suppressed.}, } @article {pmid29804207, year = {2018}, author = {Xu, X and Xu, M and Zhao, Q and Xia, Y and Chen, C and Shen, Z}, title = {Complete Genome Sequence of Cd(II)-Resistant Arthrobacter sp. PGP41, a Plant Growth-Promoting Bacterium with Potential in Microbe-Assisted Phytoremediation.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1231-1239}, pmid = {29804207}, issn = {1432-0991}, support = {31770404//National Natural Science Foundation of China/ ; 31501689//National Natural Science Foundation of China/ ; 2016T90468//China Postdoctoral Science Foundation/ ; BK20150670//Science Foundation of Jiangsu Province, China/ ; 2016YFD0800803//National Key Research and Development Program of China/ ; }, mesh = {Arthrobacter/classification/*genetics/*metabolism ; Base Sequence ; Cadmium/*metabolism/pharmacology ; Computational Biology ; DNA, Bacterial/genetics ; Genes, Bacterial ; *Genome, Bacterial ; Microbial Sensitivity Tests ; Phylogeny ; *Plant Development ; Plant Roots/microbiology ; Plants/microbiology ; RNA, Ribosomal, 16S/genetics ; Rhizosphere ; Soil Microbiology ; Soil Pollutants/metabolism/pharmacology ; }, abstract = {Microbe-assisted phytoremediation has great potential for practical applications. Plant growth-promoting bacteria (PGPB) with heavy metal (HM) resistance are important for the implementation of PGPB-assisted phytoremediation of HM-contaminated environments. Arthrobacter sp. PGP41 is a Cd(II)-resistant bacterium isolated from the rhizosphere soils of a Cd(II) hyperaccumulator plant, Solanum nigrum. Strain PGP41 can significantly improve plant seedling and root growth under Cd(II) stress conditions. This bacterium exhibited the ability to produce high levels of indole-3-acetic acid (IAA), as well as the ability to fix nitrogen and solubilize phosphate, and it possessed 1-aminocyclopropane-1-carboxylate (ACC) deaminase activity. Here, we present the complete genome sequence of strain PGP41. The genome consists of a single chromosome with a G+C content of 65.38% and no plasmids. The genome encodes 3898 genes and contains 49 tRNA and 12 rRNA genes. Multiple genes associated with plant growth promotion were identified in the genome. The whole genome sequence of PGP41 provides information useful for further clarifying the molecular mechanisms behind plant growth promotion by PGPB and facilitates its potential use as an inoculum in the bioremediation of HM-contaminated environments.}, } @article {pmid29804206, year = {2018}, author = {Zhang, Y and Feng, R and Li, L and Zhou, X and Li, Z and Jia, R and Song, X and Zou, Y and Yin, L and He, C and Liang, X and Zhou, W and Wei, Q and Du, Y and Yan, K and Wu, Z and Yin, Z}, title = {The Antibacterial Mechanism of Terpinen-4-ol Against Streptococcus agalactiae.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1214-1220}, pmid = {29804206}, issn = {1432-0991}, support = {31372477//National Natural Science Foundation of China/ ; 2012ZNY006//Program for Science and Technology Bureau of Yibin City/ ; 14TD0031//Project Supported by Scientific Research Fund of SiChuan Provincial Education Department/ ; 2013TD0015//Sichuan Youth Science and Technology Innovation Research Team for Waterfowl Disease Prevention and Control/ ; 2014HH0058//Sichuan International Cooperation Projects/ ; }, mesh = {Anti-Bacterial Agents/chemistry/*pharmacology ; Cell Membrane/metabolism/ultrastructure ; Chromatin/ultrastructure ; DNA, Bacterial/biosynthesis ; L-Lactate Dehydrogenase/metabolism ; Microbial Sensitivity Tests ; Microbial Viability/drug effects ; Molecular Structure ; Permeability/drug effects ; Protein Biosynthesis/drug effects ; Streptococcus agalactiae/*drug effects/ultrastructure ; Terpenes/chemistry/*pharmacology ; }, abstract = {Streptococcus agalactiae, a highly contagious mastitis pathogen, caused huge economic losses; meanwhile, repeated use of antibiotics results in the emergence of serious antibiotic residues and drug resistance. Therefore, it is in great need to develop ecologically sustainable antimicrobial agents. In the study, the minimal inhibitory concentration (MIC), minimal bactericidal concentration (MBC), and action mechanism of terpinen-4-ol against S. agalactiae was investigated to evaluate antibacterial activity of terpinen-4-ol. Results showed the MIC and MBC of terpinen-4-ol were 98 and 196 µg/mL, respectively. Time-kill curves displayed that the antibacterial activity of terpinen-4-ol was in a concentration-dependent manner. Transmission electron micrographs showed that the cell membrane and wall of S. agalactiae were damaged, and plasmolysis and chromatins were inconspicuous. Release of Ca2+ and Mg2+ proved that terpinen-4-ol could increase cell membrane permeability. And the release of lactate dehydrogenase (LDH) suggested that cell wall was destroyed. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) and 4',6-diamidino-2-phenylindole (DAPI) staining results showed that terpinen-4-ol could affect the synthesis of protein and DNA. These results suggested that terpinen-4-ol might be used as candidate for treating S. agalactiae infection.}, } @article {pmid29804109, year = {2018}, author = {Iezzi, ML and Lasorella, S and Varriale, G and Zagaroli, L and Ambrosi, M and Verrotti, A}, title = {Clitoromegaly in Childhood and Adolescence: Behind One Clinical Sign, a Clinical Sea.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {4}, pages = {163-174}, doi = {10.1159/000489385}, pmid = {29804109}, issn = {1661-5433}, mesh = {Adolescent ; Child ; Clitoris/*abnormalities/embryology/*pathology/physiopathology ; Female ; Humans ; Organ Size ; }, abstract = {The clitoris is a highly complex organ whose structure has only been clarified in recent years through the use of modern imaging techniques. Clitoromegaly is an abnormal enlargement of this organ. It may be congenital or acquired and is usually due to an excess of androgens in fetal life, infancy, or adolescence. Obvious clitoromegaly in individuals with ambiguous genitalia is easily identifiable, whereas borderline conditions can pass unnoticed. Case reports of clitoromegaly with or without clinical or biochemical hyperandrogenism are quite numerous. In these subjects, a comprehensive physical examination and an accurate personal and family history are needed to investigate the enlargement. We reviewed the literature on the conditions that may be involved in the development of clitoromegaly in childhood and adolescence.}, } @article {pmid29804107, year = {2018}, author = {Tanaka, A and Aoki, F and Suzuki, MG}, title = {Conserved Domains in the Transformer Protein Act Complementary to Regulate Sex-Specific Splicing of Its Own Pre-mRNA.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {4}, pages = {180-190}, doi = {10.1159/000489444}, pmid = {29804107}, issn = {1661-5433}, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; *Conserved Sequence ; Exons/genetics ; Female ; Genes, Insect ; Houseflies/*genetics ; Insect Proteins/*chemistry/*genetics/metabolism ; Male ; Protein Domains ; Protein Isoforms/genetics/metabolism ; RNA Precursors/*genetics/metabolism ; RNA Splicing/*genetics ; }, abstract = {The transformer (tra) gene, which is a female-determining master gene in the housefly Musca domestica, acts as a memory device for sex determination via its auto-regulatory function, i.e., through the contribution of the TRA protein to female-specific splicing of its own pre-mRNA. The TRA protein contains 4 small domains that are specifically conserved among TRA proteins (domains 1-4). Domain 2, also named TRA-CAM domain, is the most conserved, but its function remains unknown. To examine whether these domains are involved in the auto-regulatory function, we performed in vitro splicing assays using a tra minigene containing a partial genomic sequence of the M. domestica tra (Mdtra) gene. Co-transfection of the Mdtra minigene and an MdTRA protein expression vector into cultured insect cells strongly induced female-specific splicing of the minigene. A series of deletion mutation analyses demonstrated that these domains act complementarily to induce female-specific splicing. Domain 1 and the TRA-CAM domain were necessary for the female-specific splicing when the MdTRA protein lacked both domains 3 and 4. In this situation, mutation of the well-conserved 3 amino acids (GEG) in the TRA-CAM domain significantly reduced the female-specific splicing activity of MdTRA. GST-pull down analyses demonstrated that the MdTRA protein specifically enriched on the male-specific exonic region (exon 2b), which contains the putative TRA/TRA-2 binding sites, and that the GEG mutation disrupts this enrichment. Since the MdTRA protein interacts with its own pre-mRNA through TRA-2, our findings suggest that the conserved amino acid residues in the TRA-CAM domain may be crucial for the interaction between MdTRA and TRA-2, enhancing MdTRA recruitment on its pre-mRNA to induce female-specific splicing of tra in the housefly.}, } @article {pmid29803950, year = {2018}, author = {Foster, CSP and Henwood, MJ and Ho, SYW}, title = {Plastome sequences and exploration of tree-space help to resolve the phylogeny of riceflowers (Thymelaeaceae: Pimelea).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {156-167}, doi = {10.1016/j.ympev.2018.05.018}, pmid = {29803950}, issn = {1095-9513}, abstract = {Data sets comprising small numbers of genetic markers are not always able to resolve phylogenetic relationships. This has frequently been the case in molecular systematic studies of plants, with many analyses being based on sequence data from only two or three chloroplast genes. An example of this comes from the riceflowers Pimelea Banks & Sol. ex Gaertn. (Thymelaeaceae), a large genus of flowering plants predominantly distributed in Australia. Despite the considerable morphological variation in the genus, low sequence divergence in chloroplast markers has led to the phylogeny of Pimelea remaining largely uncertain. In this study, we resolve the backbone of the phylogeny of Pimelea in comprehensive Bayesian and maximum-likelihood analyses of plastome sequences from 41 taxa. However, some relationships received only moderate to poor support, and the Pimelea clade contained extremely short internal branches. By using topology-clustering analyses, we demonstrate that conflicting phylogenetic signals can be found across the trees estimated from individual chloroplast protein-coding genes. A relaxed-clock dating analysis reveals that Pimelea arose in the mid-Miocene, with most divergences within the genus occurring during a subsequent rapid diversification. Our new phylogenetic estimate offers better resolution and is more strongly supported than previous estimates, providing a platform for future taxonomic revisions of both Pimelea and the broader subfamily. Our study has demonstrated the substantial improvements in phylogenetic resolution that can be achieved using plastome-scale data sets in plant molecular systematics.}, } @article {pmid29803949, year = {2018}, author = {Shao, L and Li, S}, title = {Early Cretaceous greenhouse pumped higher taxa diversification in spiders.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {146-155}, doi = {10.1016/j.ympev.2018.05.026}, pmid = {29803949}, issn = {1095-9513}, abstract = {The Cretaceous experienced one of the most remarkable greenhouse periods in geological history. During this time, ecosystem reorganization significantly impacted the diversification of many groups of organisms. The rise of angiosperms marked a major biome turnover. Notwithstanding, relatively little remains known about how the Cretaceous global ecosystem impacted the evolution of spiders, which constitute one of the most abundant groups of predators. Herein, we evaluate the transcriptomes of 91 taxa representing more than half of the spider families. We add 23 newly sequenced taxa to the existing database to obtain a robust phylogenomic assessment. Phylogenetic reconstructions using different datasets and methods obtain novel placements of some groups, especially in the Synspermiata and the group having a retrolateral tibial apophysis (RTA). Molecular analyses indicate an expansion of the RTA clade at the Early Cretaceous with a hunting predatory strategy shift. Fossil analyses show a 7-fold increase of diversification rate at the same period, but this likely owes to the first occurrence of spiders in amber deposit. Additional analyses of fossil abundance show an accumulation of spider lineages in the Early Cretaceous. We speculate that the establishment of a warm greenhouse climate pumped the diversification of spiders, in particular among webless forms tracking the abundance of insect prey. Our study offers a new pathway for future investigations of spider phylogeny and diversification.}, } @article {pmid29803948, year = {2018}, author = {Recknagel, H and Kamenos, NA and Elmer, KR}, title = {Common lizards break Dollo's law of irreversibility: Genome-wide phylogenomics support a single origin of viviparity and re-evolution of oviparity.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {579-588}, doi = {10.1016/j.ympev.2018.05.029}, pmid = {29803948}, issn = {1095-9513}, mesh = {Animals ; *Biological Evolution ; Female ; Genomics ; Lizards/*classification/genetics ; *Oviparity ; Phylogeny ; *Viviparity, Nonmammalian ; }, abstract = {Dollo's law of irreversibility states that once a complex trait has been lost in evolution, it cannot be regained. It is thought that complex epistatic interactions and developmental constraints impede the re-emergence of such a trait. Oviparous reproduction (egg-laying) requires the formation of an eggshell and represents an example of such a complex trait. In reptiles, viviparity (live-bearing) has evolved repeatedly but it is highly disputed if oviparity can re-evolve. Here, using up to 194,358 SNP loci and 1,334,760 bp of sequence, we reconstruct the phylogeny of viviparous and oviparous lineages of common lizards and infer the evolutionary history of parity modes. Our phylogeny supports six main common lizard lineages that have been previously identified. We find strong statistical support for a topological arrangement that suggests a reversal to oviparity from viviparity. Our topology is consistent with highly differentiated chromosomal configurations between lineages, but disagrees with previous phylogenetic studies in some nodes. While we find high support for a reversal to oviparity, more genomic and developmental data are needed to robustly test this and assess the mechanism by which a reversal might have occurred.}, } @article {pmid29803755, year = {2018}, author = {Sangster, NC and Cowling, A and Woodgate, RG}, title = {Ten Events That Defined Anthelmintic Resistance Research.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {553-563}, doi = {10.1016/j.pt.2018.05.001}, pmid = {29803755}, issn = {1471-5007}, mesh = {Animals ; *Anthelmintics/pharmacology/therapeutic use ; *Drug Resistance/genetics ; Helminthiasis, Animal/drug therapy/*parasitology ; Helminths/drug effects/genetics ; Parasitology/economics/standards/trends ; Research/economics/*trends ; }, abstract = {Fifty years after anthelmintic resistance in livestock parasites was first reported, the prevalence of resistance has increased globally, and is of increasing significance in animal industries. It is now timely to reflect on what we have learnt, how research has unfolded, and what we hope to learn in the future. This Opinion paper examines ten important research events that were pivotal in resistance research. The moments include the discovery, description, and diagnosis of parasite resistance, as well as important physiological and genetic findings, and the development of online tools to help manage resistance. Despite our efforts, resistance remains the greatest challenge in parasite control. The future directions for research, including people and funding, are discussed.}, } @article {pmid29803646, year = {2018}, author = {Allison, WT}, title = {The intrigue is infectious: Impacts of prion protein during neural development.}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {1-3}, doi = {10.1016/j.ydbio.2018.05.019}, pmid = {29803646}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation ; Cell Survival ; Central Nervous System/*metabolism/pathology ; Dementia/*metabolism/pathology ; Humans ; Neurodegenerative Diseases/*metabolism/pathology ; *Neurogenesis ; Neurons/*metabolism/pathology ; Prions/*metabolism ; }, abstract = {Normally folded prion protein is abundant in the CNS and remarkably conserved, suggesting that it has important functions, yet these functions have remained elusive. Now the work of Parrie et al. has codified a requirement for prion protein in adult neurogenesis. Their insightful use of prion protein knockout and over-expressing mice, combined with the well-characterized olfactory system site of neurogenesis, demonstrated that prion protein promotes proliferation and survival of adult neurons. The work provides a unique independent confirmation of prion protein playing a role in neuroprotection, especially extending the conclusion beyond models using acute injury. Parrie et al. (2018) further show that prion protein is required for CNS axon guidance. A growing list of phenotypes associated with prion protein loss are coincident with symptoms of neurodegenerative disease and dementia, though it remains contentious whether any such disruption of prion protein function contributes to disease aetiology. Perhaps most intriguingly, identifying the developmental functions for prion protein opens new avenues to understand the evolution of prion protein: what history led to a CNS protein that is conserved and abundant paradoxically being both dispensable for life and the template for devastating disease?}, } @article {pmid29803645, year = {2018}, author = {Chin, JSR and Gassant, CE and Amaral, PM and Lloyd, E and Stahl, BA and Jaggard, JB and Keene, AC and Duboue, ER}, title = {Convergence on reduced stress behavior in the Mexican blind cavefish.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {319-327}, doi = {10.1016/j.ydbio.2018.05.009}, pmid = {29803645}, issn = {1095-564X}, support = {R01 GM127872/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Anxiety Agents/*pharmacology ; Behavior, Animal/*drug effects ; Buspirone/*pharmacology ; *Characiformes ; Stress, Psychological/*physiopathology ; }, abstract = {Responding appropriately to stress is essential for survival, yet in pathological states, these responses can develop into debilitating conditions such as post-traumatic stress disorder and generalized anxiety. While genetic models have provided insight into the neurochemical and neuroanatomical pathways that underlie stress, little is known about how evolutionary processes and naturally occurring variation contribute to the diverse responses to stressful stimuli observed in the animal kingdom. The Mexican cavefish is a powerful system to address how altered genetic and neuronal systems can give rise to altered behaviors. When introduced into a novel tank, surface fish and cavefish display a stereotypic stress response, characterized by reduced exploratory behavior and increased immobility, akin to "freezing". The stress response in cave and surface forms is reduced by pharmacological treatment with the anxiolytic drug, buspirone, fortifying the notion that behavior in the assay represents a conserved stress state. We find that cave populations display reduced behavioral measures of stress compared to surface conspecifics, including increased time in the top half of the tank and fewer periods of immobility. Further, reduced stress responses are observed in multiple independently derived cavefish populations, suggesting convergence on loss of behavioral stress responses in the novel tank assay. These findings provide evidence of a naturally occurring species with two drastically different forms in which a shift in predator-rich ecology to one with few predators corresponds to a reduction in stress behavior.}, } @article {pmid29803644, year = {2018}, author = {Bernstein, CS and Anderson, MT and Gohel, C and Slater, K and Gross, JM and Agarwala, S}, title = {The cellular bases of choroid fissure formation and closure.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {137-151}, doi = {10.1016/j.ydbio.2018.05.010}, pmid = {29803644}, issn = {1095-564X}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; R01 EY018005/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Chick Embryo ; Choroid/*embryology/physiology ; Coloboma/*embryology/genetics/*physiopathology ; Eye/embryology ; Mice/embryology ; Morphogenesis/physiology ; Optic Disk/embryology ; Retina/embryology ; Spatio-Temporal Analysis ; Zebrafish/embryology ; }, abstract = {Defects in choroid fissure (CF) formation and closure lead to coloboma, a major cause of childhood blindness. Despite genetic advances, the cellular defects underlying coloboma remain poorly elucidated due to our limited understanding of normal CF morphogenesis. We address this deficit by conducting high-resolution spatio-temporal analyses of CF formation and closure in the chick, mouse and fish. We show that a small ventral midline invagination initiates CF formation in the medial-proximal optic cup, subsequently extending it dorsally toward the lens, and proximally into the optic stalk. Unlike previously supposed, the optic disc does not form solely as a result of this invagination. Morphogenetic events that alter the shape of the proximal optic cup also direct clusters of outer layer and optic stalk cells to form dorsal optic disc. A cross-species comparison suggests that CF closure can be accomplished by breaking down basement membranes (BM) along the CF margins, and by establishing BM continuity along the dorsal and ventral surfaces of the CF. CF closure is subsequently accomplished via two distinct mechanisms: tissue fusion or the intercalation of various tissues into the inter-CF space. We identify several novel cell behaviors that underlie CF fusion, many of which involve remodeling of the retinal epithelium. In addition to BM disruption, these include NCAD downregulation along the SOX2+ retinal CF margin, and the protrusion or movement of partially polarized retinal cells into the inter-CF space to mediate fusion. Proximally, the inter-CF space does not fuse or narrow and is instead loosely packed with migrating SOX2+/PAX2+/Vimentin+ astrocytes until it is closed by the outgoing optic nerve. Taken together, our results highlight distinct proximal-distal differences in CF morphogenesis and closure and establish detailed cellular models that can be utilized for understanding the genetic bases of coloboma.}, } @article {pmid29803319, year = {2018}, author = {Floris, M and Olla, S and Schlessinger, D and Cucca, F}, title = {Genetic-Driven Druggable Target Identification and Validation.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {7}, pages = {558-570}, pmid = {29803319}, issn = {0168-9525}, support = {HHSN271201100005C/DA/NIDA NIH HHS/United States ; Z99 AG999999/NULL/Intramural NIH HHS/United States ; }, abstract = {Choosing the right biological target is the critical primary decision for the development of new drugs. Systematic genetic association testing of both human diseases and quantitative traits, along with resultant findings of coincident associations between them, is becoming a powerful approach to infer drug targetable candidates and generate in vitro tests to identify compounds that can modulate them therapeutically. Here, we discuss opportunities and challenges, and infer criteria for the optimal use of genetic findings in the drug discovery pipeline.}, } @article {pmid29803199, year = {2018}, author = {Machado, FA and Zahn, TMG and Marroig, G}, title = {Evolution of morphological integration in the skull of Carnivora (Mammalia): Changes in Canidae lead to increased evolutionary potential of facial traits.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13495}, pmid = {29803199}, issn = {1558-5646}, abstract = {Morphological integration refers to the fact that different phenotypic traits of organisms are not fully independent from each other, and tend to covary to different degrees. The covariation among traits is thought to reflect properties of the species' genetic architecture and thus can have an impact on evolutionary responses. Furthermore, if morphological integration changes along the history of a group, inferences of past selection regimes might be problematic. Here, we evaluated the stability and evolution of the morphological integration of skull traits in Carnivora by using evolutionary simulations and phylogenetic comparative methods. Our results show that carnivoran species are able to respond to natural selection in a very similar way. Our comparative analyses show that the phylogenetic signal for pattern of integration is lower than that observed for morphology (trait averages), and that integration was stable throughout the evolution of the group. That notwithstanding, Canidae differed from other families by having higher integration, evolvability, flexibility, and allometric coefficients on the facial region. These changes might have allowed canids to rapidly adapt to different food sources, helping to explain not only the phenotypic diversification of the family, but also why humans were able to generate such a great diversity of dog breeds through artificial selection.}, } @article {pmid29802835, year = {2018}, author = {Vega-Lopez, GA and Cerrizuela, S and Tribulo, C and Aybar, MJ}, title = {Neurocristopathies: New insights 150 years after the neural crest discovery.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.05.013}, pmid = {29802835}, issn = {1095-564X}, abstract = {The neural crest (NC) is a transient, multipotent and migratory cell population that generates an astonishingly diverse array of cell types during vertebrate development. These cells, which originate from the ectoderm in a region lateral to the neural plate in the neural fold, give rise to neurons, glia, melanocytes, chondrocytes, smooth muscle cells, odontoblasts and neuroendocrine cells, among others. Neurocristopathies (NCP) are a class of pathologies occurring in vertebrates, especially in humans that result from the abnormal specification, migration, differentiation or death of neural crest cells during embryonic development. Various pigment, skin, thyroid and hearing disorders, craniofacial and heart abnormalities, malfunctions of the digestive tract and tumors can also be considered as neurocristopathies. In this review we revisit the current classification and propose a new way to classify NCP based on the embryonic origin of the affected tissues, on recent findings regarding the molecular mechanisms that drive NC formation, and on the increased complexity of current molecular embryology techniques.}, } @article {pmid29802672, year = {2018}, author = {Lindgren, B and Orizaola, G and Laurila, A}, title = {Interacting effects of predation risk and resource level on escape speed of amphibian larvae along a latitudinal gradient.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1216-1226}, doi = {10.1111/jeb.13298}, pmid = {29802672}, issn = {1420-9101}, abstract = {Fast-growing genotypes living in time-constrained environments are often more prone to predation, suggesting that growth-predation risk trade-offs are important factors maintaining variation in growth along climatic gradients. However, the mechanisms underlying how fast growth increases predation-mediated mortality are not well understood. Here, we investigated if slow-growing, low-latitude individuals have faster escape swimming speed than fast-growing high-latitude individuals using common frog (Rana temporaria) tadpoles from eight populations collected along a 1500 km latitudinal gradient. We measured escape speed in terms of burst and endurance speeds in tadpoles raised in the laboratory at two food levels and in the presence and absence of a predator (Aeshna dragonfly larvae). We did not find any latitudinal trend in escape speed performance. In low food treatments, burst speed was higher in tadpoles reared with predators but did not differ between high-food treatments. Endurance speed, on the contrary, was lower in high-food tadpoles reared with predators and did not differ between treatments at low food levels. Tadpoles reared with predators showed inducible morphology (increased relative body size and tail depth), which had positive effects on speed endurance at low but not at high food levels. Burst speed was positively affected by tail length and tail muscle size in the absence of predators. Our results suggest that escape speed does not trade-off with fast growth along the latitudinal gradient in R. temporaria tadpoles. Instead, escape speed is a plastic trait and strongly influenced by the interaction between resource level and predation risk.}, } @article {pmid29802664, year = {2018}, author = {Henshaw, JM}, title = {Finding the one: optimal choosiness under sequential mate choice.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1193-1203}, doi = {10.1111/jeb.13296}, pmid = {29802664}, issn = {1420-9101}, abstract = {When mates are encountered sequentially, each encounter involves a decision whether to reject the current suitor and risk not finding a better mate, or to accept them despite their flaws. I provide a flexible framework for modelling optimal choosiness when mate encounters occur unpredictably in time. The model allows for temporal variation in the fitness benefits of mating, including seasonal breeding conditions, accrual of mate search costs, survival of the choosing individual or senescence of gametes. The basic optimality framework can be applied iteratively to obtain mate choice equilibria in dynamically evolving populations. My model predicts that individuals should be choosier when the average rate of mate encounters is high, but that choosiness should decline over time as the likelihood of future mate encounters decreases. When mate encounters are uncertain, there is a trade-off between reproductive timing and mate choice (the 'when' and the 'who'). Mate choice may be selected against when reproductive timing is highly important (e.g. when breeding conditions show a narrow peak in time). This can even lead to step-shaped mate choice functions, where individuals abruptly switch from rejecting to accepting all suitors as peak breeding conditions approach. The model contributes to our understanding of why individuals may not express mate preferences, even when there is substantial variation in mate quality.}, } @article {pmid29802659, year = {2018}, author = {Tilquin, A and Christie, JR and Kokko, H}, title = {Mitochondrial complementation: a possible neglected factor behind early eukaryotic sex.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1152-1164}, doi = {10.1111/jeb.13293}, pmid = {29802659}, issn = {1420-9101}, abstract = {Sex is ancestral in eukaryotes. Meiotic sex differs from bacterial ways of exchanging genetic material by involving the fusion of two cells. We examine the hypothesis that fusion evolved in early eukaryotes because it was directly beneficial, rather than a passive side effect of meiotic sex. We assume that the uptake of (proto)mitochondria into eukaryotes preceded the evolution of cell fusion and that Muller's ratchet operating within symbiont lineages led to the accumulation of lineage-specific sets of mutations in asexual host cells. We examine whether cell fusion, and the consequent biparental inheritance of symbionts, helps to mitigate the effects of this mutational meltdown of mitochondria. In our model, host cell fitness improves when two independently evolved mitochondrial strains co-inhabit a single cytoplasm, mirroring mitochondrial complementation found in modern eukaryotes. If fusion incurs no cost, we find that an allele coding for fusion can invade a population of nonfusers. If fusion is costly, there are two thresholds. The first describes a maximal fusing rate (probability of fusion per round of cell division) that is able to fix. An allele that codes for a rate above this threshold can reach a polymorphic equilibrium with nonfusers, as long as the rate is below the second threshold, above which the fusion allele is counter-selected. Whenever it evolves, fusion increases the population-wide level of heteroplasmy, which allows mitochondrial complementation and increases population fitness. We conclude that beneficial interactions between mitochondria are a potential factor that selected for cell fusion in early eukaryotes.}, } @article {pmid29802495, year = {2018}, author = {Janssen, R and Lionel, L}, title = {Embryonic expression of a Long Toll (Loto) gene in the onychophorans Euperipatoides kanangrensis and Cephalofovea clandestina.}, journal = {Development genes and evolution}, volume = {228}, number = {3-4}, pages = {171-178}, pmid = {29802495}, issn = {1432-041X}, support = {621-2011-4703//Vetenskapsrådet/International ; }, mesh = {Animals ; Arthropod Proteins/genetics/*metabolism ; Arthropods/classification/*embryology/genetics/*metabolism ; Body Patterning ; Embryo, Nonmammalian/cytology/*metabolism ; *Gene Expression Regulation, Developmental ; Morphogenesis ; Phylogeny ; }, abstract = {Recent research has shown that Toll genes, and in particular a newly defined class of Toll genes, the so-called Long Toll Genes (Loto genes), are crucial factors in embryogenesis. In arthropods, they are involved in axis formation via a process called convergent extension (CE). A hallmark of Loto genes is their relatively (compared to other Toll genes) high number of leucine-rich repeat elements (LRRs) coupled with the fact that they are expressed in transverse stripes in all segments, or a subset of segments, patterns that are reminiscent of classical segmentation genes such as the pair-rule genes. Onychophorans represent a close outgroup to the arthropods; however, their embryonic development differs substantially. It is unclear if convergent extension contributes to onychophoran germ band formation and, if so, whether Loto genes are involved in governing this process. This study identifies a single onychophoran Toll gene from a sequenced embryonic transcriptome in two onychophoran species. The identified gene shows sequence and expression pattern characteristics of Loto genes. However, its expression pattern also comprises some general differences to arthropod Loto genes that are involved in CE.}, } @article {pmid29802418, year = {2018}, author = {Xiao, F and Yu, Y and Li, J and Juneau, P and Yan, Q}, title = {Necessary Sequencing Depth and Clustering Method to Obtain Relatively Stable Diversity Patterns in Studying Fish Gut Microbiota.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1240-1246}, pmid = {29802418}, issn = {1432-0991}, support = {31672262//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Bacteria/classification/*genetics ; *Biodiversity ; *Cluster Analysis ; Computational Biology/standards ; DNA, Bacterial/genetics ; Fishes/*microbiology ; Gastrointestinal Microbiome/*genetics ; *High-Throughput Nucleotide Sequencing ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA/standards ; }, abstract = {The 16S rRNA gene is one of the most commonly used molecular markers for estimating bacterial diversity during the past decades. However, there is no consistency about the sequencing depth (from thousand to millions of sequences per sample), and the clustering methods used to generate OTUs may also be different among studies. These inconsistent premises make effective comparisons among studies difficult or unreliable. This study aims to examine the necessary sequencing depth and clustering method that would be needed to ensure a stable diversity patterns for studying fish gut microbiota. A total number of 42 samples dataset of Siniperca chuatsi (carnivorous fish) gut microbiota were used to test how the sequencing depth and clustering may affect the alpha and beta diversity patterns of fish intestinal microbiota. Interestingly, we found that the sequencing depth (resampling 1000-11,000 per sample) and the clustering methods (UPARSE and UCLUST) did not bias the estimates of the diversity patterns during the fish development from larva to adult. Although we should acknowledge that a suitable sequencing depth may differ case by case, our finding indicates that a shallow sequencing such as 1000 sequences per sample may be also enough to reflect the general diversity patterns of fish gut microbiota. However, we have shown in the present study that strict pre-processing of the original sequences is required to ensure reliable results. This study provides evidences to help making a strong scientific choice of the sequencing depth and clustering method for future studies on fish gut microbiota patterns, but at the same time reducing as much as possible the costs related to the analysis.}, } @article {pmid29802233, year = {2018}, author = {Queimado, L and Wagener, T and Ganapathy, V}, title = {Electronic cigarette aerosols induce DNA damage and reduce DNA repair: Consistency across species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5437-E5438}, pmid = {29802233}, issn = {1091-6490}, support = {R33 CA202898/CA/NCI NIH HHS/United States ; }, mesh = {*Aerosols ; DNA Damage ; DNA Repair ; *Electronic Nicotine Delivery Systems ; Nicotine ; }, } @article {pmid29802232, year = {2018}, author = {Tang, MS}, title = {Reply to Queimado et al.: E-cigarettes induce DNA damage and inhibit DNA repair in mice and human cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5439}, pmid = {29802232}, issn = {1091-6490}, mesh = {Animals ; DNA Damage ; *DNA Repair ; *Electronic Nicotine Delivery Systems ; Humans ; Mice ; }, } @article {pmid29802231, year = {2018}, author = {Sun, X and Wang, X and Tang, Z and Grivainis, M and Kahler, D and Yun, C and Mita, P and Fenyö, D and Boeke, JD}, title = {Transcription factor profiling reveals molecular choreography and key regulators of human retrotransposon expression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5526-E5535}, pmid = {29802231}, issn = {1091-6490}, support = {P01 AG051449/AG/NIA NIH HHS/United States ; P50 GM107632/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Breast Neoplasms/genetics ; Chromatin/genetics ; Female ; Gene Expression Regulation/*genetics ; Genome/genetics ; Humans ; Long Interspersed Nucleotide Elements/genetics ; Ovarian Neoplasms/genetics ; Promoter Regions, Genetic/genetics ; Protein Binding/genetics ; Regulatory Elements, Transcriptional/*genetics ; Retroelements/*genetics ; Transcription Factors/*genetics ; Transcriptome/genetics ; }, abstract = {Transposable elements (TEs) represent a substantial fraction of many eukaryotic genomes, and transcriptional regulation of these factors is important to determine TE activities in human cells. However, due to the repetitive nature of TEs, identifying transcription factor (TF)-binding sites from ChIP-sequencing (ChIP-seq) datasets is challenging. Current algorithms are focused on subtle differences between TE copies and thus bias the analysis to relatively old and inactive TEs. Here we describe an approach termed "MapRRCon" (mapping repeat reads to a consensus) which allows us to identify proteins binding to TE DNA sequences by mapping ChIP-seq reads to the TE consensus sequence after whole-genome alignment. Although this method does not assign binding sites to individual insertions in the genome, it provides a landscape of interacting TFs by capturing factors that bind to TEs under various conditions. We applied this method to screen TFs' interaction with L1 in human cells/tissues using ENCODE ChIP-seq datasets and identified 178 of the 512 TFs tested as bound to L1 in at least one biological condition with most of them (138) localized to the promoter. Among these L1-binding factors, we focused on Myc and CTCF, as they play important roles in cancer progression and 3D chromatin structure formation. Furthermore, we explored the transcriptomes of The Cancer Genome Atlas breast and ovarian tumor samples in which a consistent anti-/correlation between L1 and Myc/CTCF expression was observed, suggesting that these two factors may play roles in regulating L1 transcription during the development of such tumors.}, } @article {pmid29802230, year = {2018}, author = {Bhagi-Damodaran, A and Reed, JH and Zhu, Q and Shi, Y and Hosseinzadeh, P and Sandoval, BA and Harnden, KA and Wang, S and Sponholtz, MR and Mirts, EN and Dwaraknath, S and Zhang, Y and Moënne-Loccoz, P and Lu, Y}, title = {Heme redox potentials hold the key to reactivity differences between nitric oxide reductase and heme-copper oxidase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6195-6200}, doi = {10.1073/pnas.1720298115}, pmid = {29802230}, issn = {1091-6490}, support = {R01 GM074785/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/chemistry/metabolism ; *Heme/chemistry/metabolism ; Histidine/chemistry/metabolism ; Kinetics ; Models, Molecular ; Nitric Oxide/chemistry/metabolism ; Oxidation-Reduction ; *Oxidoreductases/chemistry/metabolism ; Spectrum Analysis ; }, abstract = {Despite high structural homology between NO reductases (NORs) and heme-copper oxidases (HCOs), factors governing their reaction specificity remain to be understood. Using a myoglobin-based model of NOR (FeBMb) and tuning its heme redox potentials (E°') to cover the native NOR range, through manipulating hydrogen bonding to the proximal histidine ligand and replacing heme b with monoformyl (MF-) or diformyl (DF-) hemes, we herein demonstrate that the E°' holds the key to reactivity differences between NOR and HCO. Detailed electrochemical, kinetic, and vibrational spectroscopic studies, in tandem with density functional theory calculations, demonstrate a strong influence of heme E°' on NO reduction. Decreasing E°' from +148 to -130 mV significantly impacts electronic properties of the NOR mimics, resulting in 180- and 633-fold enhancements in NO association and heme-nitrosyl decay rates, respectively. Our results indicate that NORs exhibit finely tuned E°' that maximizes their enzymatic efficiency and helps achieve a balance between opposite factors: fast NO binding and decay of dinitrosyl species facilitated by low E°' and fast electron transfer facilitated by high E°'. Only when E°' is optimally tuned in FeBMb(MF-heme) for NO binding, heme-nitrosyl decay, and electron transfer does the protein achieve multiple (>35) turnovers, previously not achieved by synthetic or enzyme-based NOR models. This also explains a long-standing question in bioenergetics of selective cross-reactivity in HCOs. Only HCOs with heme E°' in a similar range as NORs (between -59 and 200 mV) exhibit NOR reactivity. Thus, our work demonstrates efficient tuning of E°' in various metalloproteins for their optimal functionality.}, } @article {pmid29802229, year = {2018}, author = {Kong, T and Stone, HA and Wang, L and Shum, HC}, title = {Dynamic regimes of electrified liquid filaments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6159-6164}, pmid = {29802229}, issn = {1091-6490}, abstract = {We investigate the dynamics of an electrified liquid filament in a nozzle-to-substrate configuration with a close separation. The interplay between compressive viscous and electrostatic stresses dictates previously undocumented transitions between dynamic regimes of "jetting," "coiling," and "whipping." In particular, the onsets of both coiling and whipping instabilities are significantly influenced by the minimum radius along the liquid filament. Using a low-interfacial-tension system, we unravel the physics behind the transitions between jetting, coiling, and whipping of an electrified filament for a range of liquid properties and geometric parameters. Our results enrich the overall physical picture of the electrically forced jets, and provide insights for the emerging high-resolution instability-assisted printing of materials such as folded assemblies and scaffolds.}, } @article {pmid29802228, year = {2018}, author = {Radi, R}, title = {Oxygen radicals, nitric oxide, and peroxynitrite: Redox pathways in molecular medicine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5839-5848}, pmid = {29802228}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Biomedical Research ; Free Radicals/*metabolism ; Humans ; *Molecular Medicine ; *Nitric Oxide/metabolism/physiology ; *Oxidation-Reduction ; *Peroxynitrous Acid/metabolism/physiology ; Proteins/metabolism ; Superoxide Dismutase/metabolism ; Tyrosine/metabolism ; }, abstract = {Oxygen-derived free radicals and related oxidants are ubiquitous and short-lived intermediates formed in aerobic organisms throughout life. These reactive species participate in redox reactions leading to oxidative modifications in biomolecules, among which proteins and lipids are preferential targets. Despite a broad array of enzymatic and nonenzymatic antioxidant systems in mammalian cells and microbes, excess oxidant formation causes accumulation of new products that may compromise cell function and structure leading to cell degeneration and death. Oxidative events are associated with pathological conditions and the process of normal aging. Notably, physiological levels of oxidants also modulate cellular functions via homeostatic redox-sensitive cell signaling cascades. On the other hand, nitric oxide (•NO), a free radical and weak oxidant, represents a master physiological regulator via reversible interactions with heme proteins. The bioavailability and actions of •NO are modulated by its fast reaction with superoxide radical ([Formula: see text]), which yields an unusual and reactive peroxide, peroxynitrite, representing the merging of the oxygen radicals and •NO pathways. In this Inaugural Article, I summarize early and remarkable developments in free radical biochemistry and the later evolution of the field toward molecular medicine; this transition includes our contributions disclosing the relationship of •NO with redox intermediates and metabolism. The biochemical characterization, identification, and quantitation of peroxynitrite and its role in disease processes have concentrated much of our attention. Being a mediator of protein oxidation and nitration, lipid peroxidation, mitochondrial dysfunction, and cell death, peroxynitrite represents both a pathophysiologically relevant endogenous cytotoxin and a cytotoxic effector against invading pathogens.}, } @article {pmid29802227, year = {2018}, author = {Drown, BS and Hergenrother, PJ}, title = {Going on offense against the gram-negative defense.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6530-6532}, pmid = {29802227}, issn = {1091-6490}, support = {R01 AI136773/AI/NIAID NIH HHS/United States ; R01 GM118575/GM/NIGMS NIH HHS/United States ; }, mesh = {Gram-Negative Bacteria/*metabolism ; Lipopolysaccharides/*metabolism ; }, } @article {pmid29802026, year = {2018}, author = {Silliman, BR and He, Q}, title = {Physical Stress, Consumer Control, and New Theory in Ecology.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {492-503}, doi = {10.1016/j.tree.2018.04.015}, pmid = {29802026}, issn = {1872-8383}, abstract = {Consumer-prey interactions form the foundation of food webs and are affected by the physical environment. Multiple foundational theories in ecology [e.g., the environmental stress model (ESM), the stress-gradient hypothesis (SGH), and ecosystem resilience theory] assume increased physical stress dampens top-down control of prey. In the large majority of empirical studies, however, physical stress either does not affect or amplifies consumer control. Additive and synergistic impacts of physical stress on consumer control appear more common, for example, for herbivory versus predation, and for warm- versus cold-blooded consumers. Predictability in how physical stress affects consumer control, however, remains largely unknown. We expand classical theories in ecology so that their assumption about physical stress-consumer control relationships can be inclusive of what primarily occurs in nature.}, } @article {pmid29801773, year = {2018}, author = {Pérez-Sánchez, T and Mora-Sánchez, B and Balcázar, JL}, title = {Biological Approaches for Disease Control in Aquaculture: Advantages, Limitations and Challenges.}, journal = {Trends in microbiology}, volume = {26}, number = {11}, pages = {896-903}, doi = {10.1016/j.tim.2018.05.002}, pmid = {29801773}, issn = {1878-4380}, abstract = {Although aquaculture activity has experienced a great development over the past three decades, infectious diseases have become a limiting factor for further intensification. Because the use of antibiotics has led to the widespread emergence of antibiotic resistance, the search for alternative environmentally friendly approaches is urgently needed. This Opinion paper offers an update on the successes and challenges of biological approaches for bacterial disease prevention and control in aquaculture. Although most of these approaches are still in research and development stages, some of them have shown promising results in field trials. Therefore, a better understanding of the mechanisms of action of these approaches will help to maximise their beneficial properties.}, } @article {pmid29801772, year = {2018}, author = {Tobias, NJ and Shi, YM and Bode, HB}, title = {Refining the Natural Product Repertoire in Entomopathogenic Bacteria.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {833-840}, doi = {10.1016/j.tim.2018.04.007}, pmid = {29801772}, issn = {1878-4380}, abstract = {Members of the genera Xenorhabdus and Photorhabdus are capable of producing a huge repertoire of different natural products to support a complex life cycle involving insect pathogenesis and nematode symbiosis. Many of the natural products have direct functions, specifically targeting different facets of nematode development or the insect immune system. These adaptations have allowed the bacteria to thrive in a unique environment and become highly efficient, versatile insect pathogens. Here, we discuss the ecological advantages afforded to the bacteria by the acquisition of the gene clusters responsible for producing this repertoire of chemical compounds.}, } @article {pmid29801757, year = {2018}, author = {Duffy, S and Avery, VM}, title = {Routine In Vitro Culture of Plasmodium falciparum: Experimental Consequences?.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {564-575}, doi = {10.1016/j.pt.2018.04.005}, pmid = {29801757}, issn = {1471-5007}, mesh = {Culture Techniques/*standards ; In Vitro Techniques ; Malaria, Falciparum/parasitology ; Plasmodium falciparum/*growth & development ; Research/*standards/trends ; }, abstract = {The advent of Plasmodium falciparum (Pf) in vitro culturing opened the door for malaria research, yielding dramatic advancements in our understanding of the parasite. However, fundamental foundations taken for granted in our research endeavors can unknowingly be an Achilles heel, resulting in potential misdirection. In relation to malaria research, this could be our nonquestioning acceptance of routine in vitro culture of Pf. There is nothing routine or straightforward regarding the dynamic and intimate relationship between the parasite and the in vitro environment. Here, we discuss recent studies demonstrating the impact that slight variations in in vitro Pf culture parameters can have on scientific conclusions. We reason that culture conditions should be re-established as a primary consideration in in vitro malaria experimentation.}, } @article {pmid29801507, year = {2018}, author = {Masetti, G and Moshkelgosha, S and Köhling, HL and Covelli, D and Banga, JP and Berchner-Pfannschmidt, U and Horstmann, M and Diaz-Cano, S and Goertz, GE and Plummer, S and Eckstein, A and Ludgate, M and Biscarini, F and Marchesi, JR and , }, title = {Gut microbiota in experimental murine model of Graves' orbitopathy established in different environments may modulate clinical presentation of disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {97}, pmid = {29801507}, issn = {2049-2618}, support = {612116//FP7 People: Marie-Curie Actions/International ; BE3177/2-1//Deutsche Forschungsgemeinschaft/International ; Not applicable//Internal KCL grant/International ; }, mesh = {Animals ; Autoantibodies/immunology ; Autoimmunity/immunology ; Bacterial Load ; Disease Models, Animal ; Firmicutes/*isolation & purification ; Gastrointestinal Microbiome/*physiology ; Graves Ophthalmopathy/*pathology ; Intestines/*microbiology ; Mice ; Mice, Inbred BALB C ; RNA, Ribosomal, 16S/genetics ; Receptors, Thyrotropin/*immunology ; }, abstract = {BACKGROUND: Variation in induced models of autoimmunity has been attributed to the housing environment and its effect on the gut microbiota. In Graves' disease (GD), autoantibodies to the thyrotropin receptor (TSHR) cause autoimmune hyperthyroidism. Many GD patients develop Graves' orbitopathy or ophthalmopathy (GO) characterized by orbital tissue remodeling including adipogenesis. Murine models of GD/GO would help delineate pathogenetic mechanisms, and although several have been reported, most lack reproducibility. A model comprising immunization of female BALBc mice with a TSHR expression plasmid using in vivo electroporation was reproduced in two independent laboratories. Similar orbital disease was induced in both centers, but differences were apparent (e.g., hyperthyroidism in Center 1 but not Center 2). We hypothesized a role for the gut microbiota influencing the outcome and reproducibility of induced GO.

RESULTS: We combined metataxonomics (16S rRNA gene sequencing) and traditional microbial culture of the intestinal contents from the GO murine model, to analyze the gut microbiota in the two centers. We observed significant differences in alpha and beta diversity and in the taxonomic profiles, e.g., operational taxonomic units (OTUs) from the genus Lactobacillus were more abundant in Center 2, and Bacteroides and Bifidobacterium counts were more abundant in Center 1 where we also observed a negative correlation between the OTUs of the genus Intestinimonas and TSHR autoantibodies. Traditional microbiology largely confirmed the metataxonomics data and indicated significantly higher yeast counts in Center 1 TSHR-immunized mice. We also compared the gut microbiota between immunization groups within Center 2, comprising the TSHR- or βgal control-immunized mice and naïve untreated mice. We observed a shift of the TSHR-immunized mice bacterial communities described by the beta diversity weighted Unifrac. Furthermore, we observed a significant positive correlation between the presence of Firmicutes and orbital-adipogenesis specifically in TSHR-immunized mice.

CONCLUSIONS: The significant differences observed in microbiota composition from BALBc mice undergoing the same immunization protocol in comparable specific-pathogen-free (SPF) units in different centers support a role for the gut microbiota in modulating the induced response. The gut microbiota might also contribute to the heterogeneity of induced response since we report potential disease-associated microbial taxonomies and correlation with ocular disease.}, } @article {pmid29801503, year = {2018}, author = {Woodhouse, S and Piterman, N and Wintersteiger, CM and Göttgens, B and Fisher, J}, title = {SCNS: a graphical tool for reconstructing executable regulatory networks from single-cell genomic data.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {59}, pmid = {29801503}, issn = {1752-0509}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Reconstruction of executable mechanistic models from single-cell gene expression data represents a powerful approach to understanding developmental and disease processes. New ambitious efforts like the Human Cell Atlas will soon lead to an explosion of data with potential for uncovering and understanding the regulatory networks which underlie the behaviour of all human cells. In order to take advantage of this data, however, there is a need for general-purpose, user-friendly and efficient computational tools that can be readily used by biologists who do not have specialist computer science knowledge.

RESULTS: The Single Cell Network Synthesis toolkit (SCNS) is a general-purpose computational tool for the reconstruction and analysis of executable models from single-cell gene expression data. Through a graphical user interface, SCNS takes single-cell qPCR or RNA-sequencing data taken across a time course, and searches for logical rules that drive transitions from early cell states towards late cell states. Because the resulting reconstructed models are executable, they can be used to make predictions about the effect of specific gene perturbations on the generation of specific lineages.

CONCLUSIONS: SCNS should be of broad interest to the growing number of researchers working in single-cell genomics and will help further facilitate the generation of valuable mechanistic insights into developmental, homeostatic and disease processes.}, } @article {pmid29801464, year = {2018}, author = {Sun, X and Wu, J and Wang, G and Kang, Y and Ooi, HS and Shen, T and Wang, F and Yang, R and Xu, N and Zhao, X}, title = {Genomic analyses of unique carbohydrate and phytohormone metabolism in the macroalga Gracilariopsis lemaneiformis (Rhodophyta).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {94}, pmid = {29801464}, issn = {1471-2229}, support = {41376151//National Natural Science Foundation of China/ ; 31672674//National Natural Science Foundation of China/ ; Z17D060001//Natural Science Foundation of Zhejiang (CN)/ ; 2017D10019//Science and Technology Support Program of Ningbo (CN)/ ; }, mesh = {Carbohydrate Metabolism ; Cyclopentanes/metabolism ; Gene Ontology ; Genome, Plant/*genetics ; Genomics ; Indoleacetic Acids/metabolism ; Oxylipins/metabolism ; Phylogeny ; Plant Growth Regulators/*metabolism ; Rhodophyta/*genetics/metabolism ; Salicylic Acid/metabolism ; Seaweed/genetics/metabolism ; *Signal Transduction ; }, abstract = {BACKGROUND: Red algae are economically valuable for food and in industry. However, their genomic information is limited, and the genomic data of only a few species of red algae have been sequenced and deposited recently. In this study, we annotated a draft genome of the macroalga Gracilariopsis lemaneiformis (Gracilariales, Rhodophyta).

RESULTS: The entire 88.98 Mb genome of Gp. lemaneiformis 981 was generated from 13,825 scaffolds (≥500 bp) with an N50 length of 30,590 bp, accounting for approximately 91% of this algal genome. A total of 38.73 Mb of scaffold sequences were repetitive, and 9281 protein-coding genes were predicted. A phylogenomic analysis of 20 genomes revealed the relationship among the Chromalveolata, Rhodophyta, Chlorophyta and higher plants. Homology analysis indicated phylogenetic proximity between Gp. lemaneiformis and Chondrus crispus. The number of enzymes related to the metabolism of carbohydrates, including agar, glycoside hydrolases, glycosyltransferases, was abundant. In addition, signaling pathways associated with phytohormones such as auxin, salicylic acid and jasmonates are reported for the first time for this alga.

CONCLUSION: We sequenced and analyzed a draft genome of the red alga Gp. lemaneiformis, and revealed its carbohydrate metabolism and phytohormone signaling characteristics. This work will be helpful in research on the functional and comparative genomics of the order Gracilariales and will enrich the genomic information on marine algae.}, } @article {pmid29801463, year = {2018}, author = {Cui, XY and Du, YT and Fu, JD and Yu, TF and Wang, CT and Chen, M and Chen, J and Ma, YZ and Xu, ZS}, title = {Wheat CBL-interacting protein kinase 23 positively regulates drought stress and ABA responses.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {93}, pmid = {29801463}, issn = {1471-2229}, support = {2018ZX08009100 and 2016ZX08002-002//the National Transgenic Key Project of the Ministry of Agriculture of China/ ; }, mesh = {Abscisic Acid/*metabolism ; Arabidopsis/genetics/physiology ; Calcium-Binding Proteins/genetics/metabolism ; Droughts ; Genes, Reporter ; Germination ; Plant Growth Regulators/*metabolism ; Plant Proteins/genetics/metabolism ; Plant Roots/enzymology/genetics/physiology ; Plants, Genetically Modified ; Protein Kinases/genetics/*metabolism ; Seedlings/enzymology/genetics/physiology ; Seeds/enzymology/genetics/physiology ; *Signal Transduction ; Sodium Chloride/metabolism ; Stress, Physiological ; Triticum/*enzymology/genetics/physiology ; Two-Hybrid System Techniques ; }, abstract = {BACKGROUND: The calcineurin B-like protein (CBL)-interacting protein kinase (CIPK) signaling pathway responds to various abiotic stresses in plants.

RESULTS: Wheat CIPK23, isolated from wheat drought transcriptome data set, was induced by multiple abiotic stresses, including drought, salt, and abscisic acid (ABA). Compared with wild-type plants, TaCIPK23-overexpression wheat and Arabidopsis showed an higher survival rate under drought conditions with enhanced germination rate, developed root system, increased accumulation of osmolytes, and reduced water loss rate. Over-expression of TaCIPK23 rendered transgenic plants ABA sensitivity, as evidenced by delayed seed germination and the induction of stomatal closure. Consistent with the ABA-sensitive phenotype, the expression level of drought- and ABA-responsive genes were increased under drought conditions in the transgenic plants. In addition, using yeast two-hybrid system, pull-down and bimolecular fluorescence complementation (BiFc) assays, TaCIPK23 was found to interact with TaCBL1 on the plasma membrane.

CONCLUSIONS: These results suggest that TaCIPK23 plays important roles in ABA and drought stress responses, and mediates crosstalk between the ABA signaling pathway and drought stress responses in wheat.}, } @article {pmid29801462, year = {2018}, author = {Deyno, S and Fekadu, S and Seyfe, S}, title = {Prevalence and antimicrobial resistance of coagulase negative staphylococci clinical isolates from Ethiopia: a meta-analysis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {43}, pmid = {29801462}, issn = {1471-2180}, abstract = {BACKGROUND: Antimicrobial resistant Coagulase-negative Staphylococci (CoNS) have limited treatment options, rendered diseases untreatable and made hospitals to be reservoirs of the resistant strains. The aim of this study was to estimate the pooled prevalence and antimicrobial resistance of clinical isolates of CoNS from Ethiopia.

RESULTS: The electronic database search yielded 6511 articles of which 21 met predefined inclusion criteria. The pooled prevalence of CoNS from Ethiopia was 12% (95% confidence interval (CI): 8, 16%). The analyses revealed high level of CoNS resistance to methicilin (37%[95% CI: 21, 55%]), vancomycin (911%[95% CI: 0, 35%]), penicillin (58%[95% CI: 42, 74%]), amoxicillin (42%[95% CI: 23, 61%]), amoxicillin-clavulanate (27%[95% CI: 2, 27%]), ampicillin (64%[95% CI: 46, 80%]), tetracycline (60% [95% CI: 49, 70%]), doxycycline (36%[95% CI:19,55%]), Sulfamethoxazole-trimethoprim (50%[95% CI: 36, 64%]), ceftriaxone (27% [95% CI: 18, 38%]), cephalothin (32% [95% CI: 7, 62%]), norfloxacin (39%[95% CI: 24, 56%]), chloramphenicol (40%[95% CI: 23, 58%]), clindamycin (11% [95% CI: 2, 27%]), ciprofloxacin (14%[95% CI: 6, 22%]), gentamicin (27%[95% CI:19,36%]) and erythromycin (30%[95% CI:20%,42%]). High heterogeneity, I2 ranging from 69.04 to 96.88%; p-values ≤0.01, was observed. Eggers' test did not detect publication bias for the meta-analyses and low risk of bias was observed in included studies.

CONCLUSIONS: CoNS has gotten resistant to commonly used antimicrobials from Ethiopia. There is a need of launching national antimicrobial treatment, development and implementation of policy guidelines to contain the threat. Further research focusing on factors promoting resistance and the effect of resistance on treatment outcome studies are warranted.}, } @article {pmid29801439, year = {2018}, author = {Singh, G and Kuzniar, A and van Mulligen, EM and Gavai, A and Bachem, CW and Visser, RGF and Finkers, R}, title = {QTLTableMiner++: semantic mining of QTL tables in scientific articles.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {183}, pmid = {29801439}, issn = {1471-2105}, abstract = {BACKGROUND: A quantitative trait locus (QTL) is a genomic region that correlates with a phenotype. Most of the experimental information about QTL mapping studies is described in tables of scientific publications. Traditional text mining techniques aim to extract information from unstructured text rather than from tables. We present QTLTableMiner++ (QTM), a table mining tool that extracts and semantically annotates QTL information buried in (heterogeneous) tables of plant science literature. QTM is a command line tool written in the Java programming language. This tool takes scientific articles from the Europe PMC repository as input, extracts QTL tables using keyword matching and ontology-based concept identification. The tables are further normalized using rules derived from table properties such as captions, column headers and table footers. Furthermore, table columns are classified into three categories namely column descriptors, properties and values based on column headers and data types of cell entries. Abbreviations found in the tables are expanded using the Schwartz and Hearst algorithm. Finally, the content of QTL tables is semantically enriched with domain-specific ontologies (e.g. Crop Ontology, Plant Ontology and Trait Ontology) using the Apache Solr search platform and the results are stored in a relational database and a text file.

RESULTS: The performance of the QTM tool was assessed by precision and recall based on the information retrieved from two manually annotated corpora of open access articles, i.e. QTL mapping studies in tomato (Solanum lycopersicum) and in potato (S. tuberosum). In summary, QTM detected QTL statements in tomato with 74.53% precision and 92.56% recall and in potato with 82.82% precision and 98.94% recall.

CONCLUSION: QTM is a unique tool that aids in providing QTL information in machine-readable and semantically interoperable formats.}, } @article {pmid29801438, year = {2018}, author = {Hop, HT and Arayan, LT and Reyes, AWB and Huy, TXN and Min, WG and Lee, HJ and Rhee, MH and Chang, HH and Kim, S}, title = {Heat-stress-modulated induction of NF-κB leads to brucellacidal pro-inflammatory defense against Brucella abortus infection in murine macrophages and in a mouse model.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {44}, pmid = {29801438}, issn = {1471-2180}, abstract = {BACKGROUND: Brucella causes a chronic and debilitating infection that leads to great economic losses and a public health burden. In this study, we demonstrated the brucellacidal effect of heat shock mediated by the induction of pro-inflammatory cytokines, reactive oxygen species (ROS) accumulation and apoptosis in murine macrophages and in mice.

RESULTS: RAW264.7 cells were incubated at 43 °C, and BALB/c mice were subjected to whole body hyperthermia. The data showed a reduction in bacterial survival in the mice after daily heat exposure. This was accompanied by increased levels of cytokines TNF, IL-6, IL-1β and IFN-γ in the sera of the mice. Gene expression of NF-κB and inducible nitric oxide production were also induced in the mouse splenic cells. In parallel with the bacterial reduction in the mouse model, an increased bactericidal effect was observed in RAW264.7 cells after exposure to heat stress. In addition, the heat stress increased both the nuclear translocation of NF-κB and the expression of the heat shock proteins HSP70 and HSP90 in murine macrophages. Furthermore, heat exposure induced the increase of pro-inflammatory cytokines, ROS accumulation and apoptosis but did not affect the production of nitric oxide (NO) in macrophages.

CONCLUSION: This study demonstrated the induction of innate immune responses by heat stress that significantly reduced the intracellular survival of B. abortus in vitro and in vivo. Transcriptional factor NF-κB, which is a master regulator, could be termed a key activator of heat-induced immunity against Brucella. The increase in the expression and activation of NF-κB in splenic cells and macrophages was followed by enhanced antimicrobial effectors, including cytokines, ROS and NO that may contribute to the reduction of bacterial survival.}, } @article {pmid29801437, year = {2018}, author = {Fang, G and Jia, X and Li, H and Tan, S and Nie, Q and Yu, H and Yang, Y}, title = {Characterization of microRNA and mRNA expression profiles in skin tissue between early-feathering and late-feathering chickens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {399}, pmid = {29801437}, issn = {1471-2164}, support = {2016B020233007//the Key Project of Guangdong Province/ ; 2017.1649//The Engineering Center of Animal Breeding in Guangdong Province/ ; 2014GKXM057//the National Key Training Project/ ; }, mesh = {Animals ; Chickens/anatomy & histology/*genetics/*growth & development ; Feathers/cytology/*growth & development ; *Gene Expression Profiling ; MicroRNAs/*genetics ; RNA, Messenger/genetics ; Sequence Analysis, RNA ; Signal Transduction/genetics ; Skin/*metabolism ; Time Factors ; }, abstract = {BACKGROUND: Early feathering and late feathering in chickens are sex-linked phenotypes, which have commercial application in the poultry industry for sexing chicks at hatch and have important impacts on performance traits. However, the genetic mechanism controlling feather development and feathering patterns is unclear. Here, miRNA and mRNA expression profiles in chicken wing skin tissues were analysed through high-throughput transcriptomic sequencing, aiming to understand the biological process of follicle development and the formation of different feathering phenotypes.

RESULTS: Compared to the N1 group with no primary feathers extending out, 2893 genes and 31 miRNAs displayed significantly different expression in the F1 group with primary feathers longer than primary-covert feathers, and 1802 genes and 11 miRNAs in the L2 group displayed primary feathers shorter than primary-covert feathers. Only 201 altered genes and 3 altered miRNAs were identified between the N1 and L2 groups (fold change > 2, q value < 0.01). Both sequencing and qPCR tests revealed that PRLR was significantly decreased in the F1 and L2 groups compared to the N1 group, whereas SPEF2 was significantly decreased in the F1 group compared to the N1 or L2 group. Functional analysis revealed that the altered genes or targets of altered miRNAs were involved in multiple biological processes and pathways related to feather growth and development, such as the Wnt signalling pathway, the TGF-beta signalling pathway, the MAPK signalling pathway, epithelial cell differentiation, and limb development. Integrated analysis of miRNA and mRNA showed that 14 pairs of miRNA-mRNA negatively interacted in the process of feather formation.

CONCLUSIONS: Transcriptomic sequencing of wing skin tissues revealed large changes in F1 vs. N1 and L2 vs. N1, but few changes in F1 vs. L2 for both miRNA and mRNA expression. PRLR might only contribute to follicle development, while SPEF2 was highly related to the growth rate of primary feathers or primary-covert feathers and could be responsible for early and late feather formation. Interactions between miR-1574-5p/NR2F, miR-365-5p/JAK3 and miR-365-5p/CDK6 played important roles in hair or feather formation. In all, our results provide novel evidence to understand the molecular regulation of follicle development and feathering phenotype.}, } @article {pmid29801436, year = {2018}, author = {Opatovsky, I and Santos-Garcia, D and Ruan, Z and Lahav, T and Ofaim, S and Mouton, L and Barbe, V and Jiang, J and Zchori-Fein, E and Freilich, S}, title = {Modeling trophic dependencies and exchanges among insects' bacterial symbionts in a host-simulated environment.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {402}, pmid = {29801436}, issn = {1471-2164}, support = {1481/13//Israel Science Foundation/ ; 484/17//Israel Science Foundation/ ; }, mesh = {Animals ; Bacteria/*genetics/*metabolism ; *Environment ; Genome, Bacterial/genetics ; Hemiptera/*microbiology ; Metabolic Networks and Pathways ; *Models, Biological ; *Symbiosis ; }, abstract = {BACKGROUND: Individual organisms are linked to their communities and ecosystems via metabolic activities. Metabolic exchanges and co-dependencies have long been suggested to have a pivotal role in determining community structure. In phloem-feeding insects such metabolic interactions with bacteria enable complementation of their deprived nutrition. The phloem-feeding whitefly Bemisia tabaci (Hemiptera: Aleyrodidae) harbors an obligatory symbiotic bacterium, as well as varying combinations of facultative symbionts. This well-defined bacterial community in B. tabaci serves here as a case study for a comprehensive and systematic survey of metabolic interactions within the bacterial community and their associations with documented occurrences of bacterial combinations. We first reconstructed the metabolic networks of five common B. tabaci symbionts genera (Portiera, Rickettsia, Hamiltonella, Cardinium and Wolbachia), and then used network analysis approaches to predict: (1) species-specific metabolic capacities in a simulated bacteriocyte-like environment; (2) metabolic capacities of the corresponding species' combinations, and (3) dependencies of each species on different media components.

RESULTS: The predictions for metabolic capacities of the symbionts in the host environment were in general agreement with previously reported genome analyses, each focused on the single-species level. The analysis suggests several previously un-reported routes for complementary interactions and estimated the dependency of each symbiont in specific host metabolites. No clear association was detected between metabolic co-dependencies and co-occurrence patterns.

CONCLUSIONS: The analysis generated predictions for testable hypotheses of metabolic exchanges and co-dependencies in bacterial communities and by crossing them with co-occurrence profiles, contextualized interaction patterns into a wider ecological perspective.}, } @article {pmid29801435, year = {2018}, author = {Wang, X and Liu, J and Niu, Y and Li, Y and Zhou, S and Li, C and Ma, B and Kou, Q and Petersen, B and Sonstegard, T and Huang, X and Jiang, Y and Chen, Y}, title = {Low incidence of SNVs and indels in trio genomes of Cas9-mediated multiplex edited sheep.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {397}, pmid = {29801435}, issn = {1471-2164}, support = {31402038, 31772571//National Natural Science Foundation of China/ ; 31572369, 31572381//National Natural Science Foundation of China/ ; NXTS201601//Tan Sheep Breeding Project from Ningxia/ ; CARS-40//China Agriculture Research System/ ; }, mesh = {Animals ; CRISPR-Cas Systems/*genetics ; *Gene Editing ; *Genomics ; INDEL Mutation/*genetics ; Polymorphism, Single Nucleotide/*genetics ; Sheep/*genetics ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: The simplicity of the CRISPR/Cas9 system has enabled its widespread applications in generating animal models, functional genomic screening and in treating genetic and infectious diseases. However, unintended mutations produced by off-target CRISPR/Cas9 nuclease activity may lead to negative consequences. Especially, a very recent study found that gene editing can introduce hundreds of unintended mutations into the genome, and have attracted wide attention.

RESULTS: To address the off-target concerns, urgent characterization of the CRISPR/Cas9-mediated off-target mutagenesis is highly anticipated. Here we took advantage of our previously generated gene-edited sheep and performed family trio-based whole genome sequencing which is capable of discriminating variants in the edited progenies that are inherited, naturally generated, or induced by genetic modification. Three family trios were re-sequenced at a high average depth of genomic coverage (~ 25.8×). After developing a pipeline to comprehensively analyze the sequence data for de novo single nucleotide variants, indels and structural variations from the genome; we only found a single unintended event in the form of a 2.4 kb inversion induced by site-specific double-strand breaks between two sgRNA targeting sites at the MSTN locus with a low incidence.

CONCLUSIONS: We provide the first report on the fidelity of CRISPR-based modification for sheep genomes targeted simultaneously for gene breaks at three coding sequence locations. The trio-based sequencing approach revealed almost negligible off-target modifications, providing timely evidences of the safe application of genome editing in vivo with CRISPR/Cas9.}, } @article {pmid29801434, year = {2018}, author = {Wu, CW and Evans, JM and Huang, S and Mahoney, DW and Dukek, BA and Taylor, WR and Yab, TC and Smyrk, TC and Jen, J and Kisiel, JB and Ahlquist, DA}, title = {A Comprehensive Approach to Sequence-oriented IsomiR annotation (CASMIR): demonstration with IsomiR profiling in colorectal neoplasia.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {401}, pmid = {29801434}, issn = {1471-2164}, support = {R37 CA214679/CA/NCI NIH HHS/United States ; }, mesh = {Colon/metabolism ; Colorectal Neoplasms/*genetics ; Female ; *Gene Expression Profiling ; Humans ; Intestinal Mucosa/metabolism ; Male ; MicroRNAs/*genetics ; Middle Aged ; Molecular Sequence Annotation/*methods ; RNA Isoforms/*genetics ; *Sequence Analysis, RNA ; }, abstract = {BACKGROUND: MicroRNA (miRNA) profiling is an important step in studying biological associations and identifying marker candidates. miRNA exists in isoforms, called isomiRs, which may exhibit distinct properties. With conventional profiling methods, limitations in assay and analysis platforms may compromise isomiR interrogation.

RESULTS: We introduce a comprehensive approach to sequence-oriented isomiR annotation (CASMIR) to allow unbiased identification of global isomiRs from small RNA sequencing data. In this approach, small RNA reads are maintained as independent sequences instead of being summarized under miRNA names. IsomiR features are identified through step-wise local alignment against canonical forms and precursor sequences. Through customizing the reference database, CASMIR is applicable to isomiR annotation across species. To demonstrate its application, we investigated isomiR profiles in normal and neoplastic human colorectal epithelia. We also ran miRDeep2, a popular miRNA analysis algorithm to validate isomiRs annotated by CASMIR. With CASMIR, specific and biologically relevant isomiR patterns could be identified. We note that specific isomiRs are often more abundant than their canonical forms. We identify isomiRs that are commonly up-regulated in both colorectal cancer and advanced adenoma, and illustrate advantages in targeting isomiRs as potential biomarkers over canonical forms.

CONCLUSIONS: Studying miRNAs at the isomiR level could reveal new insight into miRNA biology and inform assay design for specific isomiRs. CASMIR facilitates comprehensive annotation of isomiR features in small RNA sequencing data for isomiR profiling and differential expression analysis.}, } @article {pmid29801433, year = {2018}, author = {Eason, K and Nyamundanda, G and Sadanandam, A}, title = {polyClustR: defining communities of reconciled cancer subtypes with biological and prognostic significance.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {182}, pmid = {29801433}, issn = {1471-2105}, abstract = {BACKGROUND: To ensure cancer patients are stratified towards treatments that are optimally beneficial, it is a priority to define robust molecular subtypes using clustering methods applied to high-dimensional biological data. If each of these methods produces different numbers of clusters for the same data, it is difficult to achieve an optimal solution. Here, we introduce "polyClustR", a tool that reconciles clusters identified by different methods into subtype "communities" using a hypergeometric test or a measure of relative proportion of common samples.

RESULTS: The polyClustR pipeline was initially tested using a breast cancer dataset to demonstrate how results are compatible with and add to the understanding of this well-characterised cancer. Two uveal melanoma datasets were then utilised to identify and validate novel subtype communities with significant metastasis-free prognostic differences and associations with known chromosomal aberrations.

CONCLUSION: We demonstrate the value of the polyClustR approach of applying multiple consensus clustering algorithms and systematically reconciling the results in identifying novel subtype communities of two cancer types, which nevertheless are compatible with established understanding of these diseases. An R implementation of the pipeline is available at: https://github.com/syspremed/polyClustR.}, } @article {pmid29801431, year = {2018}, author = {Tao, S and Wu, J and Yao, D and Chen, Y and Yang, W and Tong, C}, title = {Identification of recombination events in outbred species with next-generation sequencing data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {398}, pmid = {29801431}, issn = {1471-2164}, support = {No. 31270706//National Natural Science Foundation of China/ ; }, mesh = {Chromosome Mapping ; Genetic Markers/genetics ; Haplotypes ; *High-Throughput Nucleotide Sequencing ; *Hybridization, Genetic ; Meiosis/genetics ; Polymorphism, Single Nucleotide ; Populus/cytology/*genetics ; *Recombination, Genetic ; }, abstract = {BACKGROUND: Meiotic recombination events include crossovers and non-crossovers or gene conversions. Although the rate of crossovers is often used for genetic mapping, the gene conversion events are not well studied especially in outbred species, which could produce distorted markers and thus affect the precision of genetic maps.

RESULTS: We proposed a strategy for identifying gene conversion events in Populus with the next-generation sequencing (NGS) data from the two parents and their progeny in an F1 hybrid population. The strategy first involved phasing the heterozygous SNPs of the parents to obtain the parental haplotype blocks by NGS analytical tools, permitting to identify the parental gene conversion events with progeny genotypes. By incorporating available genetic linkage maps, longer haplotype blocks each corresponding to a chromosome can be created, not only allowing to detect crossover events but also possibly to locate a crossover in a small region. Our analysis revealed that gene conversions are more abundant than crossovers in Populus, with a higher probability to generate distorted markers in the regions involved than in the other regions on genome. The analytical procedures were implemented with Perl scripts as a freely available package, findGCO at https://github.com/tongchf/findGCO .

CONCLUSIONS: The novel strategy and the new developed Perl package permit to identify gene conversion events with the next-generation sequencing technology in a hybrid population of outbred species. The new method revealed that in a genetic mapping population some distorted genetic markers are possibly due to the gene conversion events.}, } @article {pmid29801430, year = {2018}, author = {Shi, W and Chen, S and Kong, X and Si, L and Gong, L and Zhang, Y and Yu, H}, title = {Flatfish monophyly refereed by the relationship of Psettodes in Carangimorphariae.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {400}, pmid = {29801430}, issn = {1471-2164}, support = {GG040986//Foshan University Research Start-up Project of High-caliber Personnel/ ; 31471979//National Natural Science Foundation of China (CN)/ ; 41206134//National Natural Science Foundation of China (CN)/ ; }, mesh = {Animals ; Evolution, Molecular ; Flatfishes/*genetics ; Genome, Mitochondrial/genetics ; *Phylogeny ; }, abstract = {BACKGROUND: The monophyly of flatfishes has not been supported in many molecular phylogenetic studies. The monophyly of Pleuronectoidei, which comprises all but one family of flatfishes, is broadly supported. However, the Psettodoidei, comprising the single family Psettodidae, is often found to be most closely related to other carangimorphs based on substantial sequencing efforts and diversely analytical methods. In this study, we examined why this particular result is often obtained.

RESULTS: The mitogenomes of five flatfishes were determined. Select mitogenomes of representative carangimorph species were further employed for phylogenetic and molecular clock analyses. Our phylogenetic results do not fully support Psettodes as a sister group to pleuronectoids or other carangimorphs. And results also supported the evidence of long-branch attraction between Psettodes and the adjacent clades. Two chronograms, derived from Bayesian relaxed-clock methods, suggest that over a short period in the early Paleocene, a series of important evolutionary events occurred in carangimorphs.

CONCLUSION: Based on insights provided by the molecular clock, we propose the following evolutionary explanation for the difficulty in determining the phylogenetic position of Psettodes: The initial diversification of Psettodes was very close in time to the initial diversification of carangimorphs, and the primary diversification time of pleuronectoids, the other suborder of flatfishes, occurred later than that of some percomorph taxa. Additionally, the clade of Psettodes is long and naked branch, which supports the uncertainty of its phylogenetic placement. Finally, we confirmed the monophyly of flatfishes, which was accepted by most ichthyologists.}, } @article {pmid29801429, year = {2018}, author = {Zeng, YF and Zhang, JG and Abuduhamiti, B and Wang, WT and Jia, ZQ}, title = {Phylogeographic patterns of the desert poplar in Northwest China shaped by both geology and climatic oscillations.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {75}, pmid = {29801429}, issn = {1471-2148}, support = {RIF2008-02//Fundamental Research Funds for the Central Non-profit Research Institution of Chinese Academy of Forestry/International ; 31670666//National Natural Science Foundation of China/International ; 31560127//National Natural Science Foundation of China/International ; }, mesh = {Bayes Theorem ; China ; DNA, Chloroplast/genetics ; *Desert Climate ; Gene Flow ; Genetic Variation ; *Geology ; Haplotypes/genetics ; Microsatellite Repeats/genetics ; Phylogeny ; *Phylogeography ; Population Dynamics ; Populus/*classification/genetics ; }, abstract = {BACKGROUND: The effects of historical geology and climatic events on the evolution of plants around the Qinghai-Tibetan Plateau region have been at the center of debate for years. To identify the influence of the uplift of the Tianshan Mountains and/or climatic oscillations on the evolution of plants in arid northwest China, we investigated the phylogeography of the Euphrates poplar (Populus euphratica) using chloroplast DNA (cpDNA) sequences and nuclear microsatellites, and estimated its historical distribution using Ecological Niche Modeling (ENM).

RESULTS: We found that the Euphrates poplar differed from another desert poplar, P. pruinosa, in both nuclear and chloroplast DNA. The low clonal diversity in both populations reflected the low regeneration rate by seed/seedlings in many locations. Both cpDNA and nuclear markers demonstrated a clear divergence between the Euphrates poplar populations from northern and southern Xinjiang regions. The divergence time was estimated to be early Pleistocene based on cpDNA, and late Pleistocene using an Approximate Bayesian Computation analysis based on microsatellites. Estimated gene flow was low between these two regions, and the limited gene flow occurred mainly via dispersal from eastern regions. ENM analysis supported a wider distribution of the Euphrates poplar at 3 Ma, but a more constricted distribution during both the glacial period and the interglacial period.

CONCLUSIONS: These results indicate that the deformation of the Tianshan Mountains has impeded gene flow of the Euphrates poplar populations from northern and southern Xinjiang, and the distribution constriction due to climatic oscillations further accelerated the divergence of populations from these regions. To protect the desert poplars, more effort is needed to encourage seed germination and seedling establishment, and to conserve endemic gene resources in the northern Xinjiang region.}, } @article {pmid29801418, year = {2018}, author = {Sazonovs, A and Barrett, JC}, title = {Rare-Variant Studies to Complement Genome-Wide Association Studies.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {97-112}, doi = {10.1146/annurev-genom-083117-021641}, pmid = {29801418}, issn = {1545-293X}, abstract = {Genome-wide association studies (GWASs) have revolutionized human disease genetics by discovering tens of thousands of associations between common variants and complex diseases. In parallel, huge technological advances in DNA sequencing have made it possible to measure and analyze rare variation in populations. This review considers these two stories and how they have come together. We first review the history of GWASs and sequencing. We then consider how to understand the biological mechanisms that drive signals of strong association in the absence of rare-variant studies. We describe how rare-variant studies complement these approaches and highlight both data generation and statistical challenges in their interpretation. Finally, we consider how certain special study designs, such as those for families and isolated populations, fit in this paradigm.}, } @article {pmid29800681, year = {2018}, author = {Fangous, MS and Lazzouni, I and Alexandre, Y and Gouriou, S and Boisramé, S and Vallet, S and Le Bihan, J and Ramel, S and Héry-Arnaud, G and Le Berre, R}, title = {Prevalence and dynamics of Lactobacillus sp. in the lower respiratory tract of patients with cystic fibrosis.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {222-226}, doi = {10.1016/j.resmic.2018.03.005}, pmid = {29800681}, issn = {1769-7123}, mesh = {Cystic Fibrosis/*microbiology ; Humans ; Lactobacillus/*classification/isolation & purification ; Lung/*microbiology ; Probiotics/*therapeutic use ; Pseudomonas Infections/microbiology/*therapy ; Pseudomonas aeruginosa/growth & development ; Respiratory Tract Infections/microbiology/*therapy ; }, abstract = {No prevalence or dynamics analysis of Lactobacilli in the lung of cystic fibrosis (CF) patients has yet been conducted. In order to use them as probiotics in the treatment of Pseudomonas aeruginosa infection, we describe their lung epidemiology. Over a period of 8 months, we analyzed 279 sputum samples from 124 CF patients classified according to their P. aeruginosa Leeds status of colonization. A total of 137 strains belonging to 11 species were isolated. The prevalence of carriage was 61%. No difference in species diversity or frequency was observed according to Leeds criteria. The next step will be to focus on the strain level.}, } @article {pmid29800680, year = {2018}, author = {Lavrov, KV and Shemyakina, AO and Grechishnikova, EG and Novikov, AD and Derbikov, DD and Kalinina, TI and Yanenko, AS}, title = {New cblA gene participates in regulation of cobalt-dependent transcription of nitrile hydratase genes in Rhodococcus rhodochrous.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {227-236}, doi = {10.1016/j.resmic.2018.03.006}, pmid = {29800680}, issn = {1769-7123}, mesh = {Amino Acid Sequence ; Cobalt/*metabolism ; Gene Expression Regulation, Bacterial/*genetics ; Hydro-Lyases/*genetics ; Promoter Regions, Genetic/genetics ; Rhodococcus/*genetics/metabolism ; Sequence Alignment ; Transcription, Genetic/genetics ; Transcriptional Activation/genetics ; }, abstract = {Rhodococcus strains are important biocatalysts used for biotechnological production of acrylamide catalysed by a nitrile hydratase (NHase) containing cobalt. This metalloenzyme is present at high intracellular concentrations representing up to 50% of the soluble proteins in Rhodococcus rhodochrous M8 strain. Cobalt ions were formerly reported to be essential for the synthesis of the NHase subunits, encoded by nhmBA structural genes in R. rhodochrous M8. To understand the regulatory mechanisms enabling high expression of the NHase structural genes by cobalt, two reporter genes coding for an acylamidase from Rhodococcus erythropolis TA37 and a nitrilase from Alcaligenes denitrificans C-32 were fused to the nhmBA promoter. It was shown that cobalt-dependent regulation of transcription occurs independently of another regulatory genes, nhmCD, involved in substrate-dependent regulation of transcription. Cobalt ions led to an increase (up to five-fold) in transcription of reporter genes correlated with synthesis of corresponding enzymes in R. rhodochrous recombinant strains. This led to identification of a new transcriptional regulator from the ArsR family, named CblA. Using a cblA mutant strain, it was established that CblA acted as a repressor by preventing transcription of the NHase operon promoter in the absence of cobalt ions.}, } @article {pmid29800679, year = {2018}, author = {Feranchuk, S and Belkova, N and Potapova, U and Kuzmin, D and Belikov, S}, title = {Evaluating the use of diversity indices to distinguish between microbial communities with different traits.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {254-261}, doi = {10.1016/j.resmic.2018.03.004}, pmid = {29800679}, issn = {1769-7123}, mesh = {*Algorithms ; Bacteria/*classification/*genetics ; *Biodiversity ; Coral Reefs ; DNA, Bacterial/genetics ; Ecosystem ; Metagenomics/*methods ; Microbial Consortia/*genetics ; RNA, Ribosomal, 16S/genetics ; Soil Microbiology ; }, abstract = {Several measures of biodiversity are commonly used to describe microbial communities, analyzed using 16S gene sequencing. A wide range of available experiments on 16S gene sequencing allows us to present a framework for a comparison of various diversity indices. The criterion for the comparison is the statistical significance of the difference in index values for microbial communities with different traits, within the same experiment. The results of the evaluation indicate that Shannon diversity is the most effective measure among the commonly used diversity indices. The results also indicate that, within the present framework, the Gini coefficient as a diversity index is comparable to Shannon diversity, despite the fact that the Gini coefficient, as a diversity estimator, is far less popular in microbiology than several other measures.}, } @article {pmid29800652, year = {2018}, author = {Xu, KW and Zhou, XM and Yin, QY and Zhang, L and Lu, NT and Knapp, R and Luong, TT and He, H and Fan, Q and Zhao, WY and Gao, XF and Liao, WB and Zhang, LB}, title = {A global plastid phylogeny uncovers extensive cryptic speciation in the fern genus Hymenasplenium (Aspleniaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {203-216}, doi = {10.1016/j.ympev.2018.05.021}, pmid = {29800652}, issn = {1095-9513}, abstract = {The fern genus Hymenasplenium (Aspleniaceae) is one of the two genera in the family. It is generally recognized among modern pteridologists. However, its infrageneric relationships and species diversity have been unclear and controversial. The molecular studies so far have had small taxon and character sampling. In the present study, DNA sequences of six plastid markers of 158 accessions representing ca. 40 out of ca. 50 known species of Hymenasplenium, and 16 species of Asplenium were used to infer a phylogeny with maximum likelihood, Bayesian inference, and maximum parsimony approaches. Our major results include: (1) Hymenasplenium as currently defined is strongly supported as monophyletic; (2) three major clades representing early splits in Hymenasplenium are identified, with the Old World species being strongly supported as monophyletic; it is ambiguous if the New World species are monophyletic; (3) extensive cryptic speciation in the Old World is discovered demonstrating the complexity of evolution of the genus; and (4) six strongly or moderately supported subclades in the Old World clade are revealed, differing from one another in molecular, morphological, and geographical features.}, } @article {pmid29800651, year = {2018}, author = {Tan, MH and Gan, HM and Lee, YP and Linton, S and Grandjean, F and Bartholomei-Santos, ML and Miller, AD and Austin, CM}, title = {ORDER within the chaos: Insights into phylogenetic relationships within the Anomura (Crustacea: Decapoda) from mitochondrial sequences and gene order rearrangements.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {320-331}, doi = {10.1016/j.ympev.2018.05.015}, pmid = {29800651}, issn = {1095-9513}, abstract = {The infraorder Anomura consists of a morphologically and ecologically heterogeneous group of decapod crustaceans, and has attracted interest from taxonomists for decades attempting to find some order out of the seemingly chaotic diversity within the group. Species-level diversity within the Anomura runs the gamut from the "hairy" spindly-legged yeti crab found in deep-sea hydrothermal vent environments to the largest known terrestrial invertebrate, the robust coconut or robber crab. Owing to a well-developed capacity for parallel evolution, as evidenced by the occurrence of multiple independent carcinization events, Anomura has long tested the patience and skill of both taxonomists attempting to find order, and phylogeneticists trying to establish stable hypotheses of evolutionary inter-relationships. In this study, we performed genome skimming to recover the mitogenome sequences of 12 anomuran species including the world's largest extant invertebrate, the robber crab (Birgus latro), thereby over doubling these resources for this group, together with 8 new brachyuran mitogenomes. Maximum-likelihood (ML) and Bayesian-inferred (BI) phylogenetic reconstructions based on amino acid sequences from mitogenome protein-coding genes provided strong support for the monophyly of the Anomura and Brachyura and their sister relationship, consistent with previous studies. The majority of relationships within families were supported and were largely consistent with current taxonomic classifications, whereas many relationships at higher taxonomic levels were unresolved. Nevertheless, we have strong support for a polyphyletic Paguroidea and recovered a well-supported clade of a subset of paguroids (Diogenidae + Coenobitidae) basal to all other anomurans, though this requires further testing with greater taxonomic sampling. We also introduce a new feature to the MitoPhAST bioinformatics pipeline (https://github.com/mht85/MitoPhAST) that enables the extraction of mitochondrial gene order (MGO) information directly from GenBank files and clusters groups based on common MGOs. Using this tool, we compared MGOs across the Anomura and Brachyura, identifying Anomura as a taxonomic "hot spot" with high variability in MGOs among congeneric species from multiple families while noting the broad association of highly-rearranged MGOs with several anomuran lineages inhabiting extreme niches. We also demonstrate the value of MGOs as a source of novel synapomorphies for independently reinforcing tree-based relationships and for shedding light on relationships among challenging groups such as the Aegloidea and Lomisoidea that were unresolved in phylogenetic reconstructions. Overall, this study contributes a substantial amount of new genetic material for Anomura and attempts to further resolve anomuran evolutionary relationships where possible based on a combination of sequence and MGO information. The new feature in MitoPhAST adds to the relatively limited number of bioinformatics tools available for MGO analyses, which can be utilized widely across animal groups.}, } @article {pmid29800650, year = {2018}, author = {Tomasello, S}, title = {How many names for a beloved genus? - Coalescent-based species delimitation in Xanthium L. (Ambrosiinae, Asteraceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {135-145}, doi = {10.1016/j.ympev.2018.05.024}, pmid = {29800650}, issn = {1095-9513}, abstract = {The species category is the fundamental unit in biology. In the last decades, several studies have been carried out, using sequence information and phylogenies to resolve issues in taxonomically problematic groups. The multispecies coalescent theory, and the species-delimitation methods developed in the last years based on that, offer powerful and objective tools to determine species boundaries using sequence data. The genus Xanthium is a morphologically variable complex with several local forms, nowadays become cosmopolitan due to human-mediated dispersal. Past taxonomic treatments of the genus were based essentially on the burr morphology. They varied considerably in number of recognized species, depending on the importance that the different authors gave to burr traits such as burr size, pubescence, number and length of spines in the burrs, and the degree to which those are hooked. We used sequence information from two plastid regions (the intergenic spacer regions psbA-trnH and trnQ-rps16) and two nuclear ones (ITS1-5.8 S-ITS2 rDNA, and the single-copy nuclear marker D35). Two of the most advanced coalescent-based species delimitation methods (BP&P and STACEY) were applied, in order to objectively determine species boundaries in Xanthium. Results from the species-delimitation methods strongly support scenarios with a reduced number of species. Prior on the effective population size parameter (θ) had a strong influence on BP&P results. Analyses with large and small θ prior supported species delimitation scenarios with four and five species, respectively. STACEY recognized five cluster in the dataset, all supported by high posterior probability values. Five species are identified in Xanthium, in a great extent corresponding to the infrageneric classification given for the genus in past taxonomic revisions.}, } @article {pmid29800649, year = {2018}, author = {Spano, CA and Häussermann, V and Acuña, FH and Griffiths, C and Seeb, LW and Gomez-Uchida, D}, title = {Hierarchical biogeographical processes largely explain the genomic divergence pattern in a species complex of sea anemones (Metridioidea: Sagartiidae: Anthothoe).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {217-228}, doi = {10.1016/j.ympev.2018.05.022}, pmid = {29800649}, issn = {1095-9513}, abstract = {The phylogenetic resolution provided by genome-wide data has demonstrated the usefulness of RAD sequencing to tackle long-standing taxonomic questions. Cnidarians have recently become a model group in this regard, yet species delimitation analyses have been mostly performed in octocorals. In this study, we used RAD sequencing to test the species hypotheses in a wide-spread complex of sea anemones (genus Anthothoe), contrasting this new line of evidence with their current classification. The alternative hypotheses were tested using a Bayes Factors delimitation method, and the most probable species tree was then evaluated under different biogeographic scenarios. Our results decisively rejected the current morphology-informed delimitation model and infer the presence of several cryptic species associated with distinct marine ecoregions. This spatial pattern was remarkably consistent throughout the study, highlighting the role of geographic distribution as a powerful explanatory variable of lineages diversification. The southern Gondwana pattern with episodic, jump dispersal events is the biogeographic historical representation that best fits the Anthothoe species tree. The high population differentiation possibly amplified by the occurrence of asexual reproduction makes it difficult to identify genes responsible for local adaptation, however, these seem to be mainly associated with cellular and metabolic processes. We propose a new set of species hypotheses for the Southern Hemispheric Anthothoe clade, based on the pronounced genomic divergence observed among lineages. Although the link between the genetic and phenotypic differentiation remains elusive, newer sequencing technologies are bringing us closer to understanding the evolution of sea anemone diversity and, therefore, how to appropriately classify them.}, } @article {pmid29800394, year = {2018}, author = {Schott, RK and Van Nynatten, A and Card, DC and Castoe, TA and S W Chang, B}, title = {Shifts in Selective Pressures on Snake Phototransduction Genes Associated with Photoreceptor Transmutation and Dim-Light Ancestry.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1376-1389}, doi = {10.1093/molbev/msy025}, pmid = {29800394}, issn = {1537-1719}, abstract = {The visual systems of snakes are heavily modified relative to other squamates, a condition often thought to reflect their fossorial origins. Further modifications are seen in caenophidian snakes, where evolutionary transitions between rod and cone photoreceptors, termed photoreceptor transmutations, have occurred in many lineages. Little previous work, however, has focused on the molecular evolutionary underpinnings of these morphological changes. To address this, we sequenced seven snake eye transcriptomes and utilized new whole-genome and targeted capture sequencing data. We used these data to analyze gene loss and shifts in selection pressures in phototransduction genes that may be associated with snake evolutionary origins and photoreceptor transmutation. We identified the surprising loss of rhodopsin kinase (GRK1), despite a low degree of gene loss overall and a lack of relaxed selection early during snake evolution. These results provide some of the first evolutionary genomic corroboration for a dim-light ancestor that lacks strong fossorial adaptations. Our results also indicate that snakes with photoreceptor transmutation experienced significantly different selection pressures from other reptiles. Significant positive selection was found primarily in cone-specific genes, but not rod-specific genes, contrary to our expectations. These results reveal potential molecular adaptations associated with photoreceptor transmutation and also highlight unappreciated functional differences between rod- and cone-specific phototransduction proteins. This intriguing example of snake visual system evolution illustrates how the underlying molecular components of a complex system can be reshaped in response to changing selection pressures.}, } @article {pmid29800319, year = {2018}, author = {}, title = {Neutral Theory and the Somatic Evolution of Cancer.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1561}, doi = {10.1093/molbev/msy100}, pmid = {29800319}, issn = {1537-1719}, } @article {pmid29800318, year = {2018}, author = {Caspermeyer, J}, title = {MEGA Software Celebrates Silver Anniversary.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1558-1560}, doi = {10.1093/molbev/msy098}, pmid = {29800318}, issn = {1537-1719}, } @article {pmid29800146, year = {2018}, author = {Fang, Z and Sun, D and Li, C and Sun, L and Wang, Y and Guo, M and Wang, R and Deng, Q and Hu, H and Liu, Y and Xu, D and Gooneratne, R}, title = {Regulatory effects of Shewanella putrefaciens isolated from shrimp Penaeus orientalis on the virulence factors of Vibrio parahaemolyticus and evaluation of the role of quorum sensing in virulence factors regulation.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy097}, pmid = {29800146}, issn = {1574-6941}, abstract = {As an aquatic pathogen widely present in aquatic food, Vibrio parahaemolyticus causes outbreaks of gastroenteritis across the globe. Virulence factors of V. parahaemolyticus increases with the amount of spoilage in aquatic organisms including shrimp, but mechanisms regulating its virulence factors are not well understood. In this study, five spoilage bacteria isolated from shrimp were investigated for their regulatory effects on the virulence factors including haemolysin and biofilm of V. parahaemolyticus. Among these isolates, Shewanella putrefaciens induced haemolytic activity in V. parahaemolyticus in a time-dose-temperature-dependent manner and we found the main component responsible for this effect to be the supernatant or cell-free extract of S. putrefaciens. Total haemolytic activity, expression of the thermostable direct haemolysin gene tdh and biofilm production of V. parahaemolyticus were significantly up-regulated by S. putrefaciens, but also by deletion of quorum-sensing luxM or luxS gene of V. parahaemolyticus. However, this regulation by S. putrefaciens was significantly impaired by deletion of the luxM gene, but not by deletion of the luxS gene. Further study showed that S. putrefaciens exhibited a strong degradation ability on the signalling molecule acylated homoserine lactone (AHL) synthesised by the LuxM enzyme. This study revealed a novel virulence regulatory mechanism that S. putrefaciens can significantly increase the virulence factors of V. parahaemolyticus via interfering with the luxM- type quorum-sensing signalling pathway through its AHL-degradation ability.}, } @article {pmid29800123, year = {2018}, author = {Schlatter, DC and Kahl, K and Carlson, B and Huggins, DR and Paulitz, T}, title = {Fungal community composition and diversity vary with soil depth and landscape position in a no-till wheat-based cropping system.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy098}, pmid = {29800123}, issn = {1574-6941}, abstract = {Soil edaphic characteristics are major drivers of fungal communities, but there is a lack of information on how communities vary with soil depth and landscape position in no-till cropping systems. Eastern Washington is dominated by dryland wheat grown on a highly variable landscape with steep, rolling hills. High-throughput sequencing of fungal ITS1 amplicons was used to characterize fungal communities across soil depth profiles (0 to 100 cm from the soil surface) among distinct landscape positions and aspects across a no-till wheat field. Fungal communities were highly stratified with soil depth, where deeper depths harbored distinct fungal taxa and more variable, less diverse fungal communities. Fungal communities from deep soils harbored a greater portion of taxa inferred to have pathotrophic or symbiotrophic in addition to saprotrophic lifestyles. Co-occurrence networks of fungal taxa became smaller and denser as soil depth increased. In contrast, differences between fungal communities from north-facing and south-facing slopes were relatively minor, suggesting that plant host, tillage, and fertilizer may be stronger drivers of fungal communities than landscape position.}, } @article {pmid29799802, year = {2018}, author = {Das, S and Abecasis, GR and Browning, BL}, title = {Genotype Imputation from Large Reference Panels.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {73-96}, doi = {10.1146/annurev-genom-083117-021602}, pmid = {29799802}, issn = {1545-293X}, abstract = {Genotype imputation has become a standard tool in genome-wide association studies because it enables researchers to inexpensively approximate whole-genome sequence data from genome-wide single-nucleotide polymorphism array data. Genotype imputation increases statistical power, facilitates fine mapping of causal variants, and plays a key role in meta-analyses of genome-wide association studies. Only variants that were previously observed in a reference panel of sequenced individuals can be imputed. However, the rapid increase in the number of deeply sequenced individuals will soon make it possible to assemble enormous reference panels that greatly increase the number of imputable variants. In this review, we present an overview of genotype imputation and describe the computational techniques that make it possible to impute genotypes from reference panels with millions of individuals.}, } @article {pmid29799801, year = {2018}, author = {Jayaraman, D and Bae, BI and Walsh, CA}, title = {The Genetics of Primary Microcephaly.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {177-200}, doi = {10.1146/annurev-genom-083117-021441}, pmid = {29799801}, issn = {1545-293X}, abstract = {Primary microcephaly (MCPH, for "microcephaly primary hereditary") is a disorder of brain development that results in a head circumference more than 3 standard deviations below the mean for age and gender. It has a wide variety of causes, including toxic exposures, in utero infections, and metabolic conditions. While the genetic microcephaly syndromes are relatively rare, studying these syndromes can reveal molecular mechanisms that are critical in the regulation of neural progenitor cells, brain size, and human brain evolution. Many of the causative genes for MCPH encode centrosomal proteins involved in centriole biogenesis. However, other MCPH genes fall under different mechanistic categories, notably DNA replication and repair. Recent gene discoveries and functional studies have implicated novel cellular processes, such as cytokinesis, centromere and kinetochore function, transmembrane or intracellular transport, Wnt signaling, and autophagy, as well as the apical polarity complex. Thus, MCPH genes implicate a wide variety of molecular and cellular mechanisms in the regulation of cerebral cortical size during development.}, } @article {pmid29799800, year = {2018}, author = {Markossian, S and Ang, KK and Wilson, CG and Arkin, MR}, title = {Small-Molecule Screening for Genetic Diseases.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {263-288}, doi = {10.1146/annurev-genom-083117-021452}, pmid = {29799800}, issn = {1545-293X}, abstract = {The genetic determinants of many diseases, including monogenic diseases and cancers, have been identified; nevertheless, targeted therapy remains elusive for most. High-throughput screening (HTS) of small molecules, including high-content analysis (HCA), has been an important technology for the discovery of molecular tools and new therapeutics. HTS can be based on modulation of a known disease target (called reverse chemical genetics) or modulation of a disease-associated mechanism or phenotype (forward chemical genetics). Prominent target-based successes include modulators of transthyretin, used to treat transthyretin amyloidoses, and the BCR-ABL kinase inhibitor Gleevec, used to treat chronic myelogenous leukemia. Phenotypic screening successes include modulators of cystic fibrosis transmembrane conductance regulator, splicing correctors for spinal muscular atrophy, and histone deacetylase inhibitors for cancer. Synthetic lethal screening, in which chemotherapeutics are screened for efficacy against specific genetic backgrounds, is a promising approach that merges phenotype and target. In this article, we introduce HTS technology and highlight its contributions to the discovery of drugs and probes for monogenic diseases and cancer.}, } @article {pmid29799791, year = {2018}, author = {Daniel-Ivad, M and Pimentel-Elardo, S and Nodwell, JR}, title = {Control of Specialized Metabolism by Signaling and Transcriptional Regulation: Opportunities for New Platforms for Drug Discovery?.}, journal = {Annual review of microbiology}, volume = {72}, number = {}, pages = {25-48}, doi = {10.1146/annurev-micro-022618-042458}, pmid = {29799791}, issn = {1545-3251}, abstract = {Specialized metabolites are bacterially produced small molecules that have an extraordinary diversity of important biological activities. They are useful as biochemical probes of living systems, and they have been adapted for use as drugs for human afflictions ranging from infectious diseases to cancer. The biosynthetic genes for these molecules are controlled by a dense network of regulatory mechanisms: Cell-cell signaling and nutrient sensing are conspicuous features of this network. While many components of these mechanisms have been identified, important questions about their biological roles remain shrouded in mystery. In addition to identifying new molecules and solving their mechanisms of action (a central preoccupation in this field), we suggest that addressing questions of quorum sensing versus diffusion sensing and identifying the dominant nutritional and environmental cues for specialized metabolism are important directions for research.}, } @article {pmid29799388, year = {2018}, author = {Sheu, SY and Chen, WT and Young, CC and Chen, WM}, title = {Rheinheimera coerulea sp. nov., isolated from a freshwater creek, and emended description of genus Rheinheimera Brettar et al. 2002.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2340-2347}, doi = {10.1099/ijsem.0.002838}, pmid = {29799388}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chromatiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Rivers/microbiology ; Sequence Analysis, DNA ; Taiwan ; Ubiquinone/chemistry ; }, abstract = {A bacterial strain designated TAPG2T was isolated from a freshwater creek in Taiwan and characterized using the polyphasic taxonomic approach. Cells of TAPG2T were Gram-stain negative, aerobic, motile, non-spore forming, short rods surrounded by a thick capsules and forming cream to dark-green colonies. Growth occurred at 15-37 °C (optimum, 25-30 °C), at pH 6.5-8 (optimum, pH 7) and with 0-1 % NaCl (optimum, 0.5 %). The major fatty acids (>10 %) of TAPG2T were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C18 : 1ω7c. The polar lipid profile consisted of phosphatidylethanolamine, phosphatidylglycerol, an uncharacterized aminophospholipid, an uncharacterized phospholipid, an uncharacterized aminolipid and an uncharacterized lipid. The polyamine profile was composed of the major compound putrescine and moderate amounts of spermidine. The only isoprenoid quinone was Q-8. The DNA G+C content was 53.6 mol%. Phylogenetic analyses based on 16S rRNA gene sequences indicated that TAPG2T represented a member of the genus Rheinheimera and was most closely related to Rheinheimera aquatica GR5T and Rheinheimera texasensis A62-14BT with 98.6 and 98.2 % 16S rRNA gene sequence identities, respectively. However, DNA-DNA hybridization values of TAPG2T with type strains of the species with validly published names were lower than 30 %. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that TAPG2T should be classified as representing a novel species of the genus Rheinheimera, for which the name Rheinheimera coerulea sp. nov. is presented. The type strain is TAPG2T (=BCRC 81054T=LMG 30056T=KCTC 52815T).}, } @article {pmid29799164, year = {2018}, author = {Jelen, B and Giovannelli, D and Falkowski, PG and Vetriani, C}, title = {Elemental sulfur reduction in the deep-sea vent thermophile, Thermovibrio ammonificans.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14280}, pmid = {29799164}, issn = {1462-2920}, abstract = {The reduction of elemental sulfur is an important energy-conserving pathway in prokaryotes inhabiting geothermal environments, where sulfur respiration contributes to sulfur biogeochemical cycling. Despite this, the pathways through which elemental sulfur is reduced to hydrogen sulfide remain unclear in most microorganisms. We integrated growth experiments using Thermovibrio ammonificans, a deep-sea vent thermophile that conserves energy from the oxidation of hydrogen and reduction of both nitrate and elemental sulfur, with comparative transcriptomic and proteomic approaches, coupled with scanning electron microscopy. Our results revealed that two members of the FAD-dependent pyridine nucleotide disulfide reductase family, similar to sulfide-quinone reductase and to NADH-dependent sulfur reductase (NSR), respectively, are over-expressed during sulfur respiration. Scanning electron micrographs and sulfur sequestration experiments indicated that direct access of T. ammonificans to sulfur particles strongly promoted growth. The sulfur metabolism of T. ammonificans appears to require abiotic transition from bulk elemental sulfur to polysulfide to nanoparticulate sulfur at an acidic pH, coupled to biological hydrogen oxidation. A coupled biotic-abiotic mechanism for sulfur respiration is put forward, mediated by an NSR-like protein as the terminal reductase.}, } @article {pmid29799156, year = {2018}, author = {Murfin, KE and Ginete, DR and Bashey, F and Goodrich-Blair, H}, title = {Symbiont-mediated competition: Xenorhabdus bovienii confer an advantage to their nematode host Steinernema affine by killing competitor Steinernema feltiae.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, pmid = {29799156}, issn = {1462-2920}, support = {T32 AI007414/AI/NIAID NIH HHS/United States ; T32 AI055397/AI/NIAID NIH HHS/United States ; }, abstract = {Bacterial symbionts can affect several biotic interactions of their hosts, including their competition with other species. Nematodes in the genus Steinernema utilize Xenorhabdus bacterial symbionts for insect host killing and nutritional bioconversion. Here, we establish that the Xenorhabdus bovienii bacterial symbiont (Xb-Sa-78) of Steinernema affine nematodes can impact competition between S. affine and S. feltiae by a novel mechanism, directly attacking its nematode competitor. Through co-injection and natural infection assays we demonstrate the causal role of Xb-Sa-78 in the superiority of S. affine over S. feltiae nematodes during competition. Survival assays revealed that Xb-Sa-78 bacteria kill reproductive life stages of S. feltiae. Microscopy and timed infection assays indicate that Xb-Sa-78 bacteria colonize S. feltiae nematode intestines, which alters morphology of the intestine. These data suggest that Xb-Sa-78 may be an intestinal pathogen of the non-native S. feltiae nematode, although it is a nonharmful colonizer of the native nematode host, S. affine. Screening additional X. bovienii isolates revealed that intestinal infection and killing of S. feltiae is conserved among isolates from nematodes closely related to S. affine, although the underlying killing mechanisms may vary. Together, these data demonstrate that bacterial symbionts can modulate competition between their hosts, and reinforce specificity in mutualistic interactions.}, } @article {pmid29798885, year = {2018}, author = {Elmassry, M}, title = {What I learned from teaching.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {934}, doi = {10.1126/science.360.6391.934}, pmid = {29798885}, issn = {1095-9203}, } @article {pmid29798884, year = {2018}, author = {Mimee, M and Nadeau, P and Hayward, A and Carim, S and Flanagan, S and Jerger, L and Collins, J and McDonnell, S and Swartwout, R and Citorik, RJ and Bulović, V and Langer, R and Traverso, G and Chandrakasan, AP and Lu, TK}, title = {An ingestible bacterial-electronic system to monitor gastrointestinal health.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {915-918}, doi = {10.1126/science.aas9315}, pmid = {29798884}, issn = {1095-9203}, support = {R01 EB000244/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Biosensing Techniques/*instrumentation ; Electrical Equipment and Supplies ; Gastrointestinal Diseases/*diagnosis/microbiology ; Gastrointestinal Hemorrhage/diagnosis ; Gastrointestinal Tract/*microbiology/*physiopathology ; Heme/chemistry ; Monitoring, Physiologic/*instrumentation ; *Probiotics ; Swine ; }, abstract = {Biomolecular monitoring in the gastrointestinal tract could offer rapid, precise disease detection and management but is impeded by access to the remote and complex environment. Here, we present an ingestible micro-bio-electronic device (IMBED) for in situ biomolecular detection based on environmentally resilient biosensor bacteria and miniaturized luminescence readout electronics that wirelessly communicate with an external device. As a proof of concept, we engineer heme-sensitive probiotic biosensors and demonstrate accurate diagnosis of gastrointestinal bleeding in swine. Additionally, we integrate alternative biosensors to demonstrate modularity and extensibility of the detection platform. IMBEDs enable new opportunities for gastrointestinal biomarker discovery and could transform the management and diagnosis of gastrointestinal disease.}, } @article {pmid29798883, year = {2018}, author = {Flack, A and Nagy, M and Fiedler, W and Couzin, ID and Wikelski, M}, title = {From local collective behavior to global migratory patterns in white storks.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {911-914}, doi = {10.1126/science.aap7781}, pmid = {29798883}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; Birds/*physiology ; *Flight, Animal ; *Mass Behavior ; }, abstract = {Soaring migrant birds exploit columns of rising air (thermals) to cover large distances with minimal energy. Using social information while locating thermals may benefit such birds, but examining collective movements in wild migrants has been a major challenge for researchers. We investigated the group movements of a flock of 27 naturally migrating juvenile white storks by using high-resolution GPS and accelerometers. Analyzing individual and group movements on multiple scales revealed that a small number of leaders navigated to and explored thermals, whereas followers benefited from their movements. Despite this benefit, followers often left thermals earlier and at lower height, and consequently they had to flap considerably more. Followers also migrated less far annually than did leaders. We provide insights into the interactions between freely flying social migrants and the costs and benefits of collective movement in natural populations.}, } @article {pmid29798882, year = {2018}, author = {Betts, A and Gray, C and Zelek, M and MacLean, RC and King, KC}, title = {High parasite diversity accelerates host adaptation and diversification.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {907-911}, doi = {10.1126/science.aam9974}, pmid = {29798882}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {*Adaptation, Biological ; Bacteria/virology ; Bacteriophages/physiology ; *Biodiversity ; *Evolution, Molecular ; *Host-Parasite Interactions ; }, abstract = {Host-parasite species pairs are known to coevolve, but how multiple parasites coevolve with their host is unclear. By using experimental coevolution of a host bacterium and its viral parasites, we revealed that diverse parasite communities accelerated host evolution and altered coevolutionary dynamics to enhance host resistance and decrease parasite infectivity. Increases in parasite diversity drove shifts in the mode of selection from fluctuating (Red Queen) dynamics to predominately directional (arms race) dynamics. Arms race dynamics were characterized by selective sweeps of generalist resistance mutations in the genes for the host bacterium's cell surface lipopolysaccharide (a bacteriophage receptor), which caused faster molecular evolution within host populations and greater genetic divergence among populations. These results indicate that exposure to multiple parasites influences the rate and type of host-parasite coevolution.}, } @article {pmid29798881, year = {2018}, author = {Jin, XH and Price, MB and Finnegan, JR and Boott, CE and Richter, JM and Rao, A and Menke, SM and Friend, RH and Whittell, GR and Manners, I}, title = {Long-range exciton transport in conjugated polymer nanofibers prepared by seeded growth.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {897-900}, doi = {10.1126/science.aar8104}, pmid = {29798881}, issn = {1095-9203}, abstract = {Easily processed materials with the ability to transport excitons over length scales of more than 100 nanometers are highly desirable for a range of light-harvesting and optoelectronic devices. We describe the preparation of organic semiconducting nanofibers comprising a crystalline poly(di-n-hexylfluorene) core and a solvated, segmented corona consisting of polyethylene glycol in the center and polythiophene at the ends. These nanofibers exhibit exciton transfer from the core to the lower-energy polythiophene coronas in the end blocks, which occurs in the direction of the interchain π-π stacking with very long diffusion lengths (>200 nanometers) and a large diffusion coefficient (0.5 square centimeters per second). This is made possible by the uniform exciton energetic landscape created by the well-ordered, crystalline nanofiber core.}, } @article {pmid29798880, year = {2018}, author = {Jin, C and Kim, J and Utama, MIB and Regan, EC and Kleemann, H and Cai, H and Shen, Y and Shinner, MJ and Sengupta, A and Watanabe, K and Taniguchi, T and Tongay, S and Zettl, A and Wang, F}, title = {Imaging of pure spin-valley diffusion current in WS2-WSe2 heterostructures.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {893-896}, doi = {10.1126/science.aao3503}, pmid = {29798880}, issn = {1095-9203}, abstract = {Transition metal dichalcogenide (TMDC) materials are promising for spintronic and valleytronic applications because valley-polarized excitations can be generated and manipulated with circularly polarized photons and the valley and spin degrees of freedom are locked by strong spin-orbital interactions. In this study we demonstrate efficient generation of a pure and locked spin-valley diffusion current in tungsten disulfide (WS2)-tungsten diselenide (WSe2) heterostructures without any driving electric field. We imaged the propagation of valley current in real time and space by pump-probe spectroscopy. The valley current in the heterostructures can live for more than 20 microseconds and propagate over 20 micrometers; both the lifetime and the diffusion length can be controlled through electrostatic gating. The high-efficiency and electric-field-free generation of a locked spin-valley current in TMDC heterostructures holds promise for applications in spin and valley devices.}, } @article {pmid29798879, year = {2018}, author = {Friedfeld, MR and Zhong, H and Ruck, RT and Shevlin, M and Chirik, PJ}, title = {Cobalt-catalyzed asymmetric hydrogenation of enamides enabled by single-electron reduction.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {888-893}, doi = {10.1126/science.aar6117}, pmid = {29798879}, issn = {1095-9203}, abstract = {Identifying catalyst activation modes that exploit one-electron chemistry and overcome associated deactivation pathways will be transformative for developing first-row transition metal catalysts with performance equal or, ideally, superior to precious metals. Here we describe a zinc-activation method compatible with high-throughput reaction discovery that identified scores of cobalt-phosphine combinations for the asymmetric hydrogenation of functionalized alkenes. An optimized catalyst prepared from (R,R)-Ph-BPE {Ph-BPE, 1,2-bis[(2R,5R)-2,5-diphenylphospholano]ethane} and cobalt chloride [CoCl2·6H2O] exhibited high activity and enantioselectivity in protic media and enabled the asymmetric synthesis of the epilepsy medication levetiracetam at 200-gram scale with 0.08 mole % catalyst loading. Stoichiometric studies established that the cobalt (II) catalyst precursor (R,R)-Ph-BPECoCl2 underwent ligand displacement by methanol, and zinc promoted facile one-electron reduction to cobalt (I), which more stably bound the phosphine.}, } @article {pmid29798878, year = {2018}, author = {Beck, JW and Zhou, W and Li, C and Wu, Z and White, L and Xian, F and Kong, X and An, Z}, title = {A 550,000-year record of East Asian monsoon rainfall from 10Be in loess.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {877-881}, doi = {10.1126/science.aam5825}, pmid = {29798878}, issn = {1095-9203}, abstract = {Cosmogenic 10Be flux from the atmosphere is a proxy for rainfall. Using this proxy, we derived a 550,000-year-long record of East Asian summer monsoon (EASM) rainfall from Chinese loess. This record is forced at orbital precession frequencies, with higher rainfall observed during Northern Hemisphere summer insolation maxima, although this response is damped during cold interstadials. The 10Be monsoon rainfall proxy is also highly correlated with global ice-volume variations, which differs from Chinese cave δ18O, which is only weakly correlated. We argue that both EASM intensity and Chinese cave δ18O are not governed by high-northern-latitude insolation, as suggested by others, but rather by low-latitude interhemispheric insolation gradients, which may also strongly influence global ice volume via monsoon dynamics.}, } @article {pmid29798877, year = {2018}, author = {Muhlfeld, CC and Dauwalter, DC and Kovach, RP and Kershner, JL and Williams, JE and Epifanio, J}, title = {Trout in hot water: A call for global action.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {866-867}, doi = {10.1126/science.aat8455}, pmid = {29798877}, issn = {1095-9203}, mesh = {Animals ; *Endangered Species ; *Global Warming ; Hot Temperature ; *Trout ; }, } @article {pmid29798876, year = {2018}, author = {Chen, M and Sun, Y and Yang, C and Zeng, G and Li, Z and Zhang, J}, title = {The road to wild yak protection in China.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {866}, doi = {10.1126/science.aat6749}, pmid = {29798876}, issn = {1095-9203}, mesh = {Animals ; *Cattle ; China ; Conservation of Natural Resources/*methods ; }, } @article {pmid29798875, year = {2018}, author = {}, title = {NextGen VOICES: Submit Now: Broad interests: Benefits for science.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {865}, doi = {10.1126/science.360.6391.865-b}, pmid = {29798875}, issn = {1095-9203}, } @article {pmid29798874, year = {2018}, author = {Bockmann, FA and Rodrigues, MT and Kohsldorf, T and Straker, LC and Grant, T and de Pinna, MCC and Mantelatto, FLM and Datovo, A and Pombal, JP and McNamara, JC and de Almeida, EAB and Klein, W and Hsiou, AS and Groppo, M and E Castro, RMC and de Souza Amorim, D}, title = {Brazil's government attacks biodiversity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {865}, doi = {10.1126/science.aat7540}, pmid = {29798874}, issn = {1095-9203}, mesh = {Animals ; Anura ; *Biodiversity ; Brazil ; *Federal Government ; }, } @article {pmid29798873, year = {2018}, author = {Allum, N and Besley, J and Gomez, L and Brunton-Smith, I}, title = {Disparities in science literacy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {861-862}, doi = {10.1126/science.aar8480}, pmid = {29798873}, issn = {1095-9203}, mesh = {Cognition ; Humans ; Knowledge ; Science/*education ; Socioeconomic Factors ; }, } @article {pmid29798872, year = {2018}, author = {Polymenidou, M}, title = {The RNA face of phase separation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {859-860}, doi = {10.1126/science.aat8028}, pmid = {29798872}, issn = {1095-9203}, mesh = {*RNA ; }, } @article {pmid29798871, year = {2018}, author = {Hartmann, N and Kronenberg, M}, title = {Cancer immunity thwarted by the microbiome.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {858-859}, doi = {10.1126/science.aat8289}, pmid = {29798871}, issn = {1095-9203}, support = {R01 AI137230/AI/NIAID NIH HHS/United States ; }, mesh = {Immunity ; Microbiota ; Neoplasms ; }, } @article {pmid29798870, year = {2018}, author = {Gibson, PR and Burgell, RE}, title = {Illuminating dark depths.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {856-857}, doi = {10.1126/science.aat8658}, pmid = {29798870}, issn = {1095-9203}, } @article {pmid29798869, year = {2018}, author = {Narevicius, E}, title = {Cold chemistry with two atoms.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {855-856}, doi = {10.1126/science.aat7917}, pmid = {29798869}, issn = {1095-9203}, } @article {pmid29798868, year = {2018}, author = {Holmes, RJ}, title = {Enhancing energy transport in conjugated polymers.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {854-855}, doi = {10.1126/science.aat6009}, pmid = {29798868}, issn = {1095-9203}, mesh = {*Physical Phenomena ; *Polymers ; }, } @article {pmid29798867, year = {2018}, author = {Nevitt, GA}, title = {Following the leader, for better or worse.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {852-853}, doi = {10.1126/science.aat7920}, pmid = {29798867}, issn = {1095-9203}, } @article {pmid29798866, year = {2018}, author = {Servick, K}, title = {The war on gluten.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {848-851}, doi = {10.1126/science.360.6391.848}, pmid = {29798866}, issn = {1095-9203}, mesh = {Biomarkers ; Celiac Disease/diagnosis/epidemiology/*immunology ; Diet, Gluten-Free ; Fermentation/*immunology ; Gastrointestinal Microbiome/immunology ; Glutens/adverse effects/*immunology ; Humans ; Intestines/immunology/microbiology ; Oligosaccharides/*immunology ; Triticum/adverse effects/chemistry/*immunology ; Wheat Hypersensitivity/*immunology ; }, } @article {pmid29798865, year = {2018}, author = {Hutson, M}, title = {Basic instincts.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {845-847}, doi = {10.1126/science.360.6391.845}, pmid = {29798865}, issn = {1095-9203}, mesh = {Child, Preschool ; Humans ; *Instinct ; *Machine Learning ; }, } @article {pmid29798864, year = {2018}, author = {Kupferschmidt, K}, title = {A call to arms against the other retrovirus.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {844}, doi = {10.1126/science.360.6391.844}, pmid = {29798864}, issn = {1095-9203}, } @article {pmid29798863, year = {2018}, author = {Mann, A}, title = {B612 plans asteroid hunt with fleet of small satellites.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {842-843}, doi = {10.1126/science.360.6391.842}, pmid = {29798863}, issn = {1095-9203}, } @article {pmid29798862, year = {2018}, author = {Vogel, G}, title = {German law allows use of DNA to predict suspects' looks.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {841-842}, doi = {10.1126/science.360.6391.841}, pmid = {29798862}, issn = {1095-9203}, } @article {pmid29798861, year = {2018}, author = {Normile, D}, title = {China's ambitious brain science project inches forward.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {840-841}, doi = {10.1126/science.360.6391.840}, pmid = {29798861}, issn = {1095-9203}, } @article {pmid29798860, year = {2018}, author = {Hand, E}, title = {Rival giant telescopes join to seek U.S. funding.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {839-840}, doi = {10.1126/science.360.6391.839}, pmid = {29798860}, issn = {1095-9203}, } @article {pmid29798859, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {836-838}, doi = {10.1126/science.360.6391.836}, pmid = {29798859}, issn = {1095-9203}, } @article {pmid29798858, year = {2018}, author = {Nemer, M}, title = {Canada's call.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {835}, doi = {10.1126/science.aau1744}, pmid = {29798858}, issn = {1095-9203}, } @article {pmid29798857, year = {2018}, author = {Chen, JG and Crooks, RM and Seefeldt, LC and Bren, KL and Bullock, RM and Darensbourg, MY and Holland, PL and Hoffman, B and Janik, MJ and Jones, AK and Kanatzidis, MG and King, P and Lancaster, KM and Lymar, SV and Pfromm, P and Schneider, WF and Schrock, RR}, title = {Beyond fossil fuel-driven nitrogen transformations.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, pmid = {29798857}, issn = {1095-9203}, support = {R01 GM065313/GM/NIGMS NIH HHS/United States ; }, abstract = {Nitrogen is fundamental to all of life and many industrial processes. The interchange of nitrogen oxidation states in the industrial production of ammonia, nitric acid, and other commodity chemicals is largely powered by fossil fuels. A key goal of contemporary research in the field of nitrogen chemistry is to minimize the use of fossil fuels by developing more efficient heterogeneous, homogeneous, photo-, and electrocatalytic processes or by adapting the enzymatic processes underlying the natural nitrogen cycle. These approaches, as well as the challenges involved, are discussed in this Review.}, } @article {pmid29798856, year = {2018}, author = {Ma, C and Han, M and Heinrich, B and Fu, Q and Zhang, Q and Sandhu, M and Agdashian, D and Terabe, M and Berzofsky, JA and Fako, V and Ritz, T and Longerich, T and Theriot, CM and McCulloch, JA and Roy, S and Yuan, W and Thovarai, V and Sen, SK and Ruchirawat, M and Korangy, F and Wang, XW and Trinchieri, G and Greten, TF}, title = {Gut microbiome-mediated bile acid metabolism regulates liver cancer via NKT cells.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, doi = {10.1126/science.aan5931}, pmid = {29798856}, issn = {1095-9203}, support = {ZIA BC011345/BC/NCI NIH HHS/United States ; Z01 SC004020/SC/NCI NIH HHS/United States ; Z01 BC010876/BC/NCI NIH HHS/United States ; R35 GM119438/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bile Acids and Salts/*metabolism ; Chemokine CXCL16/metabolism ; Clostridium/metabolism ; Gastrointestinal Microbiome/*immunology ; Humans ; *Immunologic Surveillance ; Liver/immunology/*metabolism/pathology ; Liver Neoplasms/*immunology/pathology ; Lymphocyte Depletion ; Mice ; Mice, Inbred C57BL ; Natural Killer T-Cells/*immunology ; Neoplasm Metastasis ; Receptors, CXCR6/metabolism ; }, abstract = {Primary liver tumors and liver metastasis currently represent the leading cause of cancer-related death. Commensal bacteria are important regulators of antitumor immunity, and although the liver is exposed to gut bacteria, their role in antitumor surveillance of liver tumors is poorly understood. We found that altering commensal gut bacteria in mice induced a liver-selective antitumor effect, with an increase of hepatic CXCR6+ natural killer T (NKT) cells and heightened interferon-γ production upon antigen stimulation. In vivo functional studies showed that NKT cells mediated liver-selective tumor inhibition. NKT cell accumulation was regulated by CXCL16 expression of liver sinusoidal endothelial cells, which was controlled by gut microbiome-mediated primary-to-secondary bile acid conversion. Our study suggests a link between gut bacteria-controlled bile acid metabolism and liver antitumor immunosurveillance.}, } @article {pmid29798855, year = {2018}, author = {LaManna, JA and Mangan, SA and Alonso, A and Bourg, NA and Brockelman, WY and Bunyavejchewin, S and Chang, LW and Chiang, JM and Chuyong, GB and Clay, K and Cordell, S and Davies, SJ and Furniss, TJ and Giardina, CP and Gunatilleke, IAUN and Gunatilleke, CVS and He, F and Howe, RW and Hubbell, SP and Hsieh, CF and Inman-Narahari, FM and Janík, D and Johnson, DJ and Kenfack, D and Korte, L and Král, K and Larson, AJ and Lutz, JA and McMahon, SM and McShea, WJ and Memiaghe, HR and Nathalang, A and Novotny, V and Ong, PS and Orwig, DA and Ostertag, R and Parker, GG and Phillips, RP and Sack, L and Sun, IF and Tello, JS and Thomas, DW and Turner, BL and Vela Díaz, DM and Vrška, T and Weiblen, GD and Wolf, A and Yap, S and Myers, JA}, title = {Response to Comment on "Plant diversity increases with the strength of negative density dependence at the global scale".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, doi = {10.1126/science.aar5245}, pmid = {29798855}, issn = {1095-9203}, mesh = {*Biodiversity ; Ecosystem ; Seedlings ; *Trees ; }, abstract = {Chisholm and Fung claim that our method of estimating conspecific negative density dependence (CNDD) in recruitment is systematically biased, and present an alternative method that shows no latitudinal pattern in CNDD. We demonstrate that their approach produces strongly biased estimates of CNDD, explaining why they do not detect a latitudinal pattern. We also address their methodological concerns using an alternative distance-weighted approach, which supports our original findings of a latitudinal gradient in CNDD and a latitudinal shift in the relationship between CNDD and species abundance.}, } @article {pmid29798854, year = {2018}, author = {Chisholm, RA and Fung, T}, title = {Comment on "Plant diversity increases with the strength of negative density dependence at the global scale".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, doi = {10.1126/science.aar4685}, pmid = {29798854}, issn = {1095-9203}, mesh = {*Biodiversity ; *Ecosystem ; Plants ; Trees ; }, abstract = {LaManna et al (Reports, 30 June 2017, p. 1389) found higher conspecific negative density dependence in tree communities at lower latitudes, yielding a possible mechanistic explanation for the latitudinal diversity gradient. We show that their results are artifacts of a selective data transformation and a forced zero intercept in their fitted model. A corrected analysis shows no latitudinal trend.}, } @article {pmid29798853, year = {2018}, author = {LaManna, JA and Mangan, SA and Alonso, A and Bourg, NA and Brockelman, WY and Bunyavejchewin, S and Chang, LW and Chiang, JM and Chuyong, GB and Clay, K and Cordell, S and Davies, SJ and Furniss, TJ and Giardina, CP and Gunatilleke, IAUN and Gunatilleke, CVS and He, F and Howe, RW and Hubbell, SP and Hsieh, CF and Inman-Narahari, FM and Janík, D and Johnson, DJ and Kenfack, D and Korte, L and Král, K and Larson, AJ and Lutz, JA and McMahon, SM and McShea, WJ and Memiaghe, HR and Nathalang, A and Novotny, V and Ong, PS and Orwig, DA and Ostertag, R and Parker, GG and Phillips, RP and Sack, L and Sun, IF and Tello, JS and Thomas, DW and Turner, BL and Vela Díaz, DM and Vrška, T and Weiblen, GD and Wolf, A and Yap, S and Myers, JA}, title = {Response to Comment on "Plant diversity increases with the strength of negative density dependence at the global scale".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, doi = {10.1126/science.aar3824}, pmid = {29798853}, issn = {1095-9203}, mesh = {*Biodiversity ; Population Density ; Seedlings ; *Trees ; }, abstract = {Hülsmann and Hartig suggest that ecological mechanisms other than specialized natural enemies or intraspecific competition contribute to our estimates of conspecific negative density dependence (CNDD). To address their concern, we show that our results are not the result of a methodological artifact and present a null-model analysis that demonstrates that our original findings-(i) stronger CNDD at tropical relative to temperate latitudes and (ii) a latitudinal shift in the relationship between CNDD and species abundance-persist even after controlling for other processes that might influence spatial relationships between adults and recruits.}, } @article {pmid29798852, year = {2018}, author = {Hülsmann, L and Hartig, F}, title = {Comment on "Plant diversity increases with the strength of negative density dependence at the global scale".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, doi = {10.1126/science.aar2435}, pmid = {29798852}, issn = {1095-9203}, mesh = {*Biodiversity ; *Ecosystem ; Population Density ; Trees ; }, abstract = {LaManna et al (Reports, 30 June 2017, p. 1389) claim that subadult trees are proportionally less common at high conspecific adult density (CNDD) and that this effect increases toward the tropics and for rare species. We show that the CNDD-abundance correlation may have arisen from a methodological artifact and that a range of processes can explain the reported latitudinal pattern.}, } @article {pmid29798816, year = {2018}, author = {Binney, N}, title = {The function of the heart is not obvious.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {68-69}, number = {}, pages = {56-69}, doi = {10.1016/j.shpsc.2018.05.003}, pmid = {29798816}, issn = {1879-2499}, mesh = {Heart/*physiology ; Heart Failure/classification/*history/physiopathology ; History, 20th Century ; History, 21st Century ; Humans ; Philosophy, Medical/*history ; }, abstract = {It is widely believed that the function of the heart is obviously to pump blood. I argue here that it is not. The definition, presentation, and pathophysiological explanation of heart failure, as well as the measurement of cardiac dysfunction, are not as might be expected if the function of the heart was simply to pump blood. Far from being obvious, many central features of heart failure are still being investigated. This has important implications for philosophical debates about health and disease. According to naturalists like Christopher Boorse, medical practice is founded on a well-established body of physiological knowledge, which provides the one true account of the biological function of organs. On this naturalistic view, there should only be one account of the pathophysiology of heart failure in use in medical practice. This account of the pathophysiology of heart failure should be well-established, as opposed to uncertain. Medics should use this physiological knowledge to inform their clinical practice, and not vice versa. Clinical considerations, such as whether patients respond to therapy, should not inform debates about what the pathophysiology of heart failure is. I will show this is not the case. The handling of knowledge of the biological function of the heart in medical practice differs substantially from Boorse's account.}, } @article {pmid29797781, year = {2018}, author = {Maharjan, RP and Ferenci, T}, title = {The impact of growth rate and environmental factors on mutation rates and spectra in Escherichia coli.}, journal = {Environmental microbiology reports}, volume = {10}, number = {6}, pages = {626-633}, doi = {10.1111/1758-2229.12661}, pmid = {29797781}, issn = {1758-2229}, abstract = {Genetic variation in bacterial populations is remarkably sensitive to environmental influences, including simple, nutritional differences. Not only the rate but also the kind of mutational changes is biased by the nutritional state of bacteria. Here we investigate the mutational consequences of a universal variable for free-living bacteria, namely the growth rate. By controlling growth in chemostats, the rate and mix of mutations was investigated for populations of Escherichia coli subject to different specific growth rates. Both aerobic and anaerobic cultures were compared with see if growth rate is a factor in the commonest respiratory conditions for E. coli. We find mutation rates are raised markedly with decreasing growth rate. Base pair substitutions and 1-bp insertions and deletions increase with reduced growth rate, but less so in anaerobic cultures. Insertion sequence movements are particularly sensitive to growth rate, with IS2 being optimal at intermediate growth rates whereas IS1 and IS150 movements are highest at the slowest tested growth rate. A comprehensive comparison of growth rate effects, as well as six other environmental factors, provides the most complete picture yet of the range of mutational signatures in bacterial genetic variation.}, } @article {pmid29797774, year = {2018}, author = {Kabekkodu, SP and Shukla, V and Varghese, VK and D' Souza, J and Chakrabarty, S and Satyamoorthy, K}, title = {Clustered miRNAs and their role in biological functions and diseases.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1955-1986}, doi = {10.1111/brv.12428}, pmid = {29797774}, issn = {1469-185X}, abstract = {MicroRNAs (miRNAs) are endogenous, small non-coding RNAs known to regulate expression of protein-coding genes. A large proportion of miRNAs are highly conserved, localized as clusters in the genome, transcribed together from physically adjacent miRNAs and show similar expression profiles. Since a single miRNA can target multiple genes and miRNA clusters contain multiple miRNAs, it is important to understand their regulation, effects and various biological functions. Like protein-coding genes, miRNA clusters are also regulated by genetic and epigenetic events. These clusters can potentially regulate every aspect of cellular function including growth, proliferation, differentiation, development, metabolism, infection, immunity, cell death, organellar biogenesis, messenger signalling, DNA repair and self-renewal, among others. Dysregulation of miRNA clusters leading to altered biological functions is key to the pathogenesis of many diseases including carcinogenesis. Here, we review recent advances in miRNA cluster research and discuss their regulation and biological functions in pathological conditions.}, } @article {pmid29797769, year = {2018}, author = {Beinart, RA and Rotterová, J and Čepička, I and Gast, RJ and Edgcomb, VP}, title = {The genome of an endosymbiotic methanogen is very similar to those of its free-living relatives.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2538-2551}, doi = {10.1111/1462-2920.14279}, pmid = {29797769}, issn = {1462-2920}, abstract = {The methanogenic endosymbionts of anaerobic protists represent the only known intracellular archaea, yet, almost nothing is known about genome structure and content in these lineages. Here, an almost complete genome of an intracellular Methanobacterium species was assembled from a metagenome derived from its host ciliate, a Heterometopus species. Phylogenomic analysis showed that the endosymbiont was closely related to free-living Methanobacterium isolates, and when compared with the genomes of free-living Methanobacterium, the endosymbiont did not show significant reduction in genome size or GC content. Additionally, the Methanobacterium endosymbiont genome shared the majority of its genes with its closest relative, though it did also contain unique genes possibly involved in interactions with the host via membrane-associated proteins, the removal of toxic by-products from host metabolism and the production of small signalling molecules. Though anaerobic ciliates have been shown to transmit their endosymbionts to daughter cells during division, the results presented here could suggest that the endosymbiotic Methanobacterium did not experience significant genetic isolation or drift and/or that this lineage was only recently acquired. Altogether, comparative genomic analysis identified genes potentially involved in the establishment and maintenance of the symbiosis, as well provided insight into the genomic consequences for an intracellular archaeum.}, } @article {pmid29797757, year = {2018}, author = {Unno, T and Staley, C and Brown, CM and Han, D and Sadowsky, MJ and Hur, HG}, title = {Fecal pollution: new trends and challenges in microbial source tracking using next-generation sequencing.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3132-3140}, doi = {10.1111/1462-2920.14281}, pmid = {29797757}, issn = {1462-2920}, support = {//The Korea Ministry of Environment (MOE)/ ; 2016001350006//Environmental Health Action Program/ ; //Basic Science Research Program/ ; //National Research Foundation of Korea (NRF)/ ; 2016R1A6A1A03012862//Ministry of Education/ ; //GIST Research Institute (GRI)/ ; NA14OAR4170080//United States Department of Commerce/ ; 2T32GM0083-21A1//University of Minnesota NIH Biotechnology Training Grant/ ; }, abstract = {In this minireview, we expand upon traditional microbial source tracking (MST) methods by discussing two recently developed, next-generation-sequencing (NGS)-based MST approaches to identify sources of fecal pollution in recreational waters. One method defines operational taxonomic units (OTUs) that are specific to a fecal source, e.g., humans and animals or shared among multiple fecal sources to determine the magnitude and likely source association of fecal pollution. The other method uses SourceTracker, a program using a Bayesian algorithm, to determine which OTUs have contributed to an environmental community based on the composition of microbial communities in multiple fecal sources. Contemporary NGS-based MST tools offer a promising avenue to rapidly characterize fecal source contributions for water monitoring and remediation efforts at a broader and more efficient scale than previous molecular MST methods. However, both NGS methods require optimized sequence processing methodologies (e.g. quality filtering and clustering algorithms) and are influenced by primer selection for amplicon sequencing. Therefore, care must be taken when extrapolating data or combining datasets. Furthermore, traditional limitations of library-dependent MST methods, including differential decay of source material in environmental waters and spatiotemporal variation in source communities, remain to be fully understood. Nevertheless, increasing use of these methods, as well as expanding fecal taxon libraries representative of source communities, will help improve the accuracy of these methods and provide promising tools for future MST investigations.}, } @article {pmid29796877, year = {2018}, author = {Forsythe, JG and English, SL and Simoneaux, RE and Weber, AL}, title = {Synthesis of β-Peptide Standards for Use in Model Prebiotic Reactions.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {2}, pages = {201-211}, pmid = {29796877}, issn = {1573-0875}, support = {CHE-1504217)//NSF and NASA/ ; }, mesh = {Chromatography, High Pressure Liquid ; Hydrolysis ; *Origin of Life ; Peptides/*chemical synthesis ; beta-Alanine/chemistry/*standards ; }, abstract = {A one-pot method was developed for the preparation of a series of β-alanine standards of moderate size (2 to ≥12 residues) for studies concerning the prebiotic origins of peptides. The one-pot synthesis involved two sequential reactions: (1) dry-down self-condensation of β-alanine methyl ester, yielding β-alanine peptide methyl ester oligomers, and (2) subsequent hydrolysis of β-alanine peptide methyl ester oligomers, producing a series of β-alanine peptide standards. These standards were then spiked into a model prebiotic product mixture to confirm by HPLC the formation of β-alanine peptides under plausible reaction conditions. The simplicity of this approach suggests it can be used to prepare a variety of β-peptide standards for investigating differences between α- and β-peptides in the context of prebiotic chemistry.}, } @article {pmid29796853, year = {2018}, author = {He, P and Wang, H and Luo, J and Yan, Y and Chen, Z}, title = {A Real-Time PCR with Melting Curve Analysis for Molecular Typing of Vibrio parahaemolyticus.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1206-1213}, pmid = {29796853}, issn = {1432-0991}, support = {2017AY33071//Science and Technology Program of Jiaxing City/ ; 2013AY21051-1//Science and Technology Program of Jiaxing City/ ; }, mesh = {Cluster Analysis ; Foodborne Diseases/microbiology ; Humans ; Multigene Family/genetics ; Multilocus Sequence Typing/*methods ; *Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Temperature ; Vibrio Infections/*microbiology ; Vibrio parahaemolyticus/*classification/genetics ; }, abstract = {Foodborne disease caused by Vibrio parahaemolyticus is a serious public health problem in many countries. Molecular typing has a great scientific significance and application value for epidemiological research of V. parahaemolyticus. In this study, a real-time PCR with melting curve analysis was established for molecular typing of V. parahaemolyticus. Eighteen large variably presented gene clusters (LVPCs) of V. parahaemolyticus which have different distributions in the genome of different strains were selected as targets. Primer pairs of 18 LVPCs were distributed into three tubes. To validate this newly developed assay, we tested 53 Vibrio parahaemolyticus strains, which were classified in 13 different types. Furthermore, cluster analysis using NTSYS PC 2.02 software could divide 53 V. parahaemolyticus strains into six clusters at a relative similarity coefficient of 0.85. This method is fast, simple, and conveniently for molecular typing of V. parahaemolyticus.}, } @article {pmid29796852, year = {2018}, author = {Jiang, Y and Lu, J and Chen, T and Yan, W and Dong, W and Zhou, J and Zhang, W and Ma, J and Jiang, M and Xin, F}, title = {The Draft Genome Sequence of Clostridium sp. Strain NJ4, a Bacterium Capable of Producing Butanol from Inulin Through Consolidated Bioprocessing.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1221-1225}, pmid = {29796852}, issn = {1432-0991}, support = {BK20170993//the Jiangsu Province Natural Science Foundation for Youths/ ; BK20170997//the Jiangsu Province Natural Science Foundation for Youths/ ; KL16-08//the Project of State Key Laboratory of Materials-Oriented Chemical Engineering/ ; BE2016389//the Key Science and Technology Project of Jiangsu Province/ ; GPKLMB201702//the Foundation of Guangdong Provincial Key Laboratory of Marine Biotechnology/ ; 21706125//the National Natural Science Foundation of China/ ; 21727818//the National Natural Science Foundation of China/ ; 21706124//the National Natural Science Foundation of China/ ; 31700092//the National Natural Science Foundation of China/ ; }, mesh = {Alcohol Dehydrogenase/genetics ; Aldehyde Dehydrogenase/genetics ; Base Sequence ; Bioreactors/*microbiology ; Biosynthetic Pathways ; Butanols/*metabolism ; Clostridium/*genetics/metabolism ; Computational Biology ; DNA, Bacterial/genetics ; Databases, Genetic ; *Genome, Bacterial ; Glycoside Hydrolases/genetics/metabolism ; Inulin/*metabolism ; RNA, Ribosomal, 16S/genetics ; }, abstract = {A novel butanogenic Clostridium sp. NJ4 was successfully isolated and characterized, which could directly produce relatively high titer of butanol from inulin through consolidated bioprocessing (CBP). The assembled draft genome of strain NJ4 is 4.09 Mp, containing 3891 encoded protein sequences with G+C content of 30.73%. Among these annotated genes, a levanase, a hypothetical inulinase, and two bifunctional alcohol/aldehyde dehydrogenases (AdhE) were found to play key roles in the achievement of ABE production from inulin through CBP.}, } @article {pmid29796663, year = {2018}, author = {Ali Mubaraki, M and Ahmad, M and Hafiz, TA and Marie, MA}, title = {The therapeutic prospect of crosstalk between prokaryotic and eukaryotic organisms in the human gut.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy065}, pmid = {29796663}, issn = {1574-6941}, abstract = {The peaceful phenomenon of the co-evolution between the prokaryotes (microbiota) and the eukaryotes (parasites including protozoa and helminths) in the animal gut has drawn the researchers' attention. Importantly, exploring the potential of helminths for therapeutic uses was one of the reasons behind understanding the physiological and immunological crosstalk existing between them. Here we discuss the interactive immunological associations of helminths and microbial responses individually and in combination with their hosts. Considering that there is probably crosstalk between eukaryotic organisms like helminths and protozoa with their host's gut microbiota, in this review we searched the literature identifying the privileged and favourable relationship generated between them in the host. Understanding the possibilities of the role of helminths along with gut microbiota as a black box would certainly help decode the therapeutic intrusion with helminths in experimental clinical trials, and a successful trial could be used to consider possible future and safe treatments for various immune-inflammatory diseases in humans.}, } @article {pmid29796643, year = {2018}, author = {Arciero, E and Kraaijenbrink, T and Asan, and Haber, M and Mezzavilla, M and Ayub, Q and Wang, W and Pingcuo, Z and Yang, H and Wang, J and Jobling, MA and van Driem, G and Xue, Y and de Knijff, P and Tyler-Smith, C}, title = {Demographic History and Genetic Adaptation in the Himalayan Region Inferred from Genome-Wide SNP Genotypes of 49 Populations.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1916-1933}, pmid = {29796643}, issn = {1537-1719}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {We genotyped 738 individuals belonging to 49 populations from Nepal, Bhutan, North India, or Tibet at over 500,000 SNPs, and analyzed the genotypes in the context of available worldwide population data in order to investigate the demographic history of the region and the genetic adaptations to the harsh environment. The Himalayan populations resembled other South and East Asians, but in addition displayed their own specific ancestral component and showed strong population structure and genetic drift. We also found evidence for multiple admixture events involving Himalayan populations and South/East Asians between 200 and 2,000 years ago. In comparisons with available ancient genomes, the Himalayans, like other East and South Asian populations, showed similar genetic affinity to Eurasian hunter-gatherers (a 24,000-year-old Upper Palaeolithic Siberian), and the related Bronze Age Yamnaya. The high-altitude Himalayan populations all shared a specific ancestral component, suggesting that genetic adaptation to life at high altitude originated only once in this region and subsequently spread. Combining four approaches to identifying specific positively selected loci, we confirmed that the strongest signals of high-altitude adaptation were located near the Endothelial PAS domain-containing protein 1 and Egl-9 Family Hypoxia Inducible Factor 1 loci, and discovered eight additional robust signals of high-altitude adaptation, five of which have strong biological functional links to such adaptation. In conclusion, the demographic history of Himalayan populations is complex, with strong local differentiation, reflecting both genetic and cultural factors; these populations also display evidence of multiple genetic adaptations to high-altitude environments.}, } @article {pmid29796593, year = {2018}, author = {Schmidt, JE and Gaudin, ACM}, title = {What is the agronomic potential of biofertilizers for maize? A meta-analysis.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy094}, pmid = {29796593}, issn = {1574-6941}, abstract = {Biofertilizers are promoted as a strategy for sustainable intensification of agriculture, but their efficacy varies widely among published studies and it is unclear whether they deliver the promised benefits. Studies are commonly conducted under controlled conditions prior to deployment in the field, yet the predictive value of such studies for field-scale productivity has not been critically examined. A meta-analysis was conducted using a novel host crop-specific approach to evaluate the agronomic potential of bacterial biofertilizers for maize. Yield increases tended to be slightly higher and more variable in greenhouse studies using field soil than in the field, and greenhouse studies poorly predicted the influence of moderating climate, soil and taxonomic variables. We found greater efficacy of Azospirillum spp. and lower efficacy of Bacillus spp. and Enterobacter spp. under field conditions. Surprisingly, biofertilizer strains with confirmed plant-growth-promoting traits such as phosphorus solubilization, nitrogen fixation and phytohormone production in vitro were associated with lower yields in the field than strains not confirmed to possess these traits; only 1-aminocyclopropane-1-carboxylate deaminase synthesis increased yields. These results indicate the need for a novel biofertilizer development framework that integrates information from native soil microbial communities and prioritizes field validation of results.}, } @article {pmid29795541, year = {2018}, author = {Lázár, V and Martins, A and Spohn, R and Daruka, L and Grézal, G and Fekete, G and Számel, M and Jangir, PK and Kintses, B and Csörgő, B and Nyerges, Á and Györkei, Á and Kincses, A and Dér, A and Walter, FR and Deli, MA and Urbán, E and Hegedűs, Z and Olajos, G and Méhi, O and Bálint, B and Nagy, I and Martinek, TA and Papp, B and Pál, C}, title = {Antibiotic-resistant bacteria show widespread collateral sensitivity to antimicrobial peptides.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {718-731}, doi = {10.1038/s41564-018-0164-0}, pmid = {29795541}, issn = {2058-5276}, abstract = {Antimicrobial peptides are promising alternative antimicrobial agents. However, little is known about whether resistance to small-molecule antibiotics leads to cross-resistance (decreased sensitivity) or collateral sensitivity (increased sensitivity) to antimicrobial peptides. We systematically addressed this question by studying the susceptibilities of a comprehensive set of 60 antibiotic-resistant Escherichia coli strains towards 24 antimicrobial peptides. Strikingly, antibiotic-resistant bacteria show a high frequency of collateral sensitivity to antimicrobial peptides, whereas cross-resistance is relatively rare. We identify clinically relevant multidrug-resistance mutations that increase bacterial sensitivity to antimicrobial peptides. Collateral sensitivity in multidrug-resistant bacteria arises partly through regulatory changes shaping the lipopolysaccharide composition of the bacterial outer membrane. These advances allow the identification of antimicrobial peptide-antibiotic combinations that enhance antibiotic activity against multidrug-resistant bacteria and slow down de novo evolution of resistance. In particular, when co-administered as an adjuvant, the antimicrobial peptide glycine-leucine-amide caused up to 30-fold decrease in the antibiotic resistance level of resistant bacteria. Our work provides guidelines for the development of efficient peptide-based therapies of antibiotic-resistant infections.}, } @article {pmid29795540, year = {2018}, author = {Washburne, AD and Morton, JT and Sanders, J and McDonald, D and Zhu, Q and Oliverio, AM and Knight, R}, title = {Methods for phylogenetic analysis of microbiome data.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {652-661}, doi = {10.1038/s41564-018-0156-0}, pmid = {29795540}, issn = {2058-5276}, abstract = {How does knowing the evolutionary history of microorganisms affect our analysis of microbiological datasets? Depending on the research question, the common ancestry of microorganisms can be a source of confounding variation, or a scaffolding used for inference. For example, when performing regression on traits, common ancestry is a source of dependence among observations, whereas when searching for clades with correlated abundances, common ancestry is the scaffolding for inference. The common ancestry of microorganisms and their genes are organized in trees-phylogenies-which can and should be incorporated into analyses of microbial datasets. While there has been a recent expansion of phylogenetically informed analytical tools, little guidance exists for which method best answers which biological questions. Here, we review methods for phylogeny-aware analyses of microbiome datasets, considerations for choosing the appropriate method and challenges inherent in these methods. We introduce a conceptual organization of these tools, breaking them down into phylogenetic comparative methods, ancestral state reconstruction and analysis of phylogenetic variables and distances, and provide examples in Supplementary Online Tutorials. Careful consideration of the research question and ecological and evolutionary assumptions will help researchers choose a phylogeny and appropriate methods to produce accurate, biologically informative and previously unreported insights.}, } @article {pmid29795539, year = {2018}, author = {Teske, A}, title = {Aerobic Archaea in iron-rich springs.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {646-647}, doi = {10.1038/s41564-018-0168-9}, pmid = {29795539}, issn = {2058-5276}, } @article {pmid29795538, year = {2018}, author = {Lee, B and Bubeck Wardenburg, J}, title = {A common approach to toxin specificity.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {644-645}, doi = {10.1038/s41564-018-0173-z}, pmid = {29795538}, issn = {2058-5276}, support = {R01 AI097434/AI/NIAID NIH HHS/United States ; }, } @article {pmid29795537, year = {2018}, author = {}, title = {CRISPR still needs microbiologists.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {641}, doi = {10.1038/s41564-018-0175-x}, pmid = {29795537}, issn = {2058-5276}, } @article {pmid29795536, year = {2018}, author = {Carlton, JM}, title = {Evolution of human malaria.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {642-643}, doi = {10.1038/s41564-018-0170-2}, pmid = {29795536}, issn = {2058-5276}, } @article {pmid29795524, year = {2018}, author = {Stark, PB}, title = {Before reproducibility must come preproducibility.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {613}, doi = {10.1038/d41586-018-05256-0}, pmid = {29795524}, issn = {1476-4687}, mesh = {Animals ; Humans ; Mice ; Peer Review, Research/*standards ; Reproducibility of Results ; Research Report/*standards ; Software ; *Terminology as Topic ; }, } @article {pmid29795354, year = {2018}, author = {Salje, H and Cummings, DAT and Rodriguez-Barraquer, I and Katzelnick, LC and Lessler, J and Klungthong, C and Thaisomboonsuk, B and Nisalak, A and Weg, A and Ellison, D and Macareo, L and Yoon, IK and Jarman, R and Thomas, S and Rothman, AL and Endy, T and Cauchemez, S}, title = {Reconstruction of antibody dynamics and infection histories to evaluate dengue risk.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {719-723}, pmid = {29795354}, issn = {1476-4687}, support = {P01 AI034533/AI/NIAID NIH HHS/United States ; R01 AI114703/AI/NIAID NIH HHS/United States ; }, mesh = {Adolescent ; Antibodies, Viral/blood/*immunology ; Bayes Theorem ; Child ; Cohort Studies ; Dengue/blood/*immunology/*transmission ; Dengue Vaccines/immunology ; *Disease Susceptibility ; Hemagglutination Inhibition Tests ; Humans ; Models, Biological ; Risk ; Seasons ; }, abstract = {As with many pathogens, most dengue infections are subclinical and therefore unobserved 1 . Coupled with limited understanding of the dynamic behaviour of potential serological markers of infection, this observational problem has wide-ranging implications, including hampering our understanding of individual- and population-level correlates of infection and disease risk and how these change over time, between assay interpretations and with cohort design. Here we develop a framework that simultaneously characterizes antibody dynamics and identifies subclinical infections via Bayesian augmentation from detailed cohort data (3,451 individuals with blood draws every 91 days, 143,548 haemagglutination inhibition assay titre measurements)2,3. We identify 1,149 infections (95% confidence interval, 1,135-1,163) that were not detected by active surveillance and estimate that 65% of infections are subclinical. After infection, individuals develop a stable set point antibody load after one year that places them within or outside a risk window. Individuals with pre-existing titres of ≤1:40 develop haemorrhagic fever 7.4 (95% confidence interval, 2.5-8.2) times more often than naive individuals compared to 0.0 times for individuals with titres >1:40 (95% confidence interval: 0.0-1.3). Plaque reduction neutralization test titres ≤1:100 were similarly associated with severe disease. Across the population, variability in the size of epidemics results in large-scale temporal changes in infection and disease risk that correlate poorly with age.}, } @article {pmid29795353, year = {2018}, author = {Shi, SL and Wong, ZL and Buchwald, SL}, title = {Addendum: Copper-catalysed enantioselective stereodivergent synthesis of amino alcohols.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {E3}, doi = {10.1038/s41586-018-0112-4}, pmid = {29795353}, issn = {1476-4687}, } @article {pmid29795352, year = {2018}, author = {Tumino, A and Spitaleri, C and La Cognata, M and Cherubini, S and Guardo, GL and Gulino, M and Hayakawa, S and Indelicato, I and Lamia, L and Petrascu, H and Pizzone, RG and Puglia, SMR and Rapisarda, GG and Romano, S and Sergi, ML and Spartá, R and Trache, L}, title = {An increase in the 12C + 12C fusion rate from resonances at astrophysical energies.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {687-690}, doi = {10.1038/s41586-018-0149-4}, pmid = {29795352}, issn = {1476-4687}, abstract = {Carbon burning powers scenarios that influence the fate of stars, such as the late evolutionary stages of massive stars 1 (exceeding eight solar masses) and superbursts from accreting neutron stars2,3. It proceeds through the 12C + 12C fusion reactions that produce an alpha particle and neon-20 or a proton and sodium-23-that is, 12C(12C, α)20Ne and 12C(12C, p)23Na-at temperatures greater than 0.4 × 109 kelvin, corresponding to astrophysical energies exceeding a megaelectronvolt, at which such nuclear reactions are more likely to occur in stars. The cross-sections 4 for those carbon fusion reactions (probabilities that are required to calculate the rate of the reactions) have hitherto not been measured at the Gamow peaks 4 below 2 megaelectronvolts because of exponential suppression arising from the Coulomb barrier. The reference rate 5 at temperatures below 1.2 × 109 kelvin relies on extrapolations that ignore the effects of possible low-lying resonances. Here we report the measurement of the 12C(12C, α0,1)20Ne and 12C(12C, p0,1)23Na reaction rates (where the subscripts 0 and 1 stand for the ground and first excited states of 20Ne and 23Na, respectively) at centre-of-mass energies from 2.7 to 0.8 megaelectronvolts using the Trojan Horse method6,7 and the deuteron in 14N. The cross-sections deduced exhibit several resonances that are responsible for very large increases of the reaction rate at relevant temperatures. In particular, around 5 × 108 kelvin, the reaction rate is boosted to more than 25 times larger than the reference value 5 . This finding may have implications such as lowering the temperatures and densities 8 required for the ignition of carbon burning in massive stars and decreasing the superburst ignition depth in accreting neutron stars to reconcile observations with theoretical models 3 .}, } @article {pmid29795351, year = {2018}, author = {Ostapcuk, V and Mohn, F and Carl, SH and Basters, A and Hess, D and Iesmantavicius, V and Lampersberger, L and Flemr, M and Pandey, A and Thomä, NH and Betschinger, J and Bühler, M}, title = {Activity-dependent neuroprotective protein recruits HP1 and CHD4 to control lineage-specifying genes.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {739-743}, doi = {10.1038/s41586-018-0153-8}, pmid = {29795351}, issn = {1476-4687}, mesh = {Animals ; Cell Lineage/*genetics ; Chromosomal Proteins, Non-Histone/*metabolism ; DNA Helicases/*metabolism ; Euchromatin/genetics/metabolism ; Homeodomain Proteins/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mouse Embryonic Stem Cells/cytology ; Nerve Tissue Proteins/genetics/*metabolism ; Neurons/cytology ; Nucleosomes/metabolism ; Protein Binding ; Repressor Proteins/metabolism ; Transcription, Genetic ; }, abstract = {De novo mutations in ADNP, which encodes activity-dependent neuroprotective protein (ADNP), have recently been found to underlie Helsmoortel-Van der Aa syndrome, a complex neurological developmental disorder that also affects several other organ functions 1 . ADNP is a putative transcription factor that is essential for embryonic development 2 . However, its precise roles in transcriptional regulation and development are not understood. Here we show that ADNP interacts with the chromatin remodeller CHD4 and the chromatin architectural protein HP1 to form a stable complex, which we refer to as ChAHP. Besides mediating complex assembly, ADNP recognizes DNA motifs that specify binding of ChAHP to euchromatin. Genetic ablation of ChAHP components in mouse embryonic stem cells results in spontaneous differentiation concomitant with premature activation of lineage-specific genes and in a failure to differentiate towards the neuronal lineage. Molecularly, ChAHP-mediated repression is fundamentally different from canonical HP1-mediated silencing: HP1 proteins, in conjunction with histone H3 lysine 9 trimethylation (H3K9me3), are thought to assemble broad heterochromatin domains that are refractory to transcription. ChAHP-mediated repression, however, acts in a locally restricted manner by establishing inaccessible chromatin around its DNA-binding sites and does not depend on H3K9me3-modified nucleosomes. Together, our results reveal that ADNP, via the recruitment of HP1 and CHD4, regulates the expression of genes that are crucial for maintaining distinct cellular states and assures accurate cell fate decisions upon external cues. Such a general role of ChAHP in governing cell fate plasticity may explain why ADNP mutations affect several organs and body functions and contribute to cancer progression1,3,4. Notably, we found that the integrity of the ChAHP complex is disrupted by nonsense mutations identified in patients with Helsmoortel-Van der Aa syndrome, and this could be rescued by aminoglycosides that suppress translation termination 5 . Therefore, patients might benefit from therapeutic agents that are being developed to promote ribosomal read-through of premature stop codons6,7.}, } @article {pmid29795350, year = {2018}, author = {Merckx, T and Souffreau, C and Kaiser, A and Baardsen, LF and Backeljau, T and Bonte, D and Brans, KI and Cours, M and Dahirel, M and Debortoli, N and De Wolf, K and Engelen, JMT and Fontaneto, D and Gianuca, AT and Govaert, L and Hendrickx, F and Higuti, J and Lens, L and Martens, K and Matheve, H and Matthysen, E and Piano, E and Sablon, R and Schön, I and Van Doninck, K and De Meester, L and Van Dyck, H}, title = {Body-size shifts in aquatic and terrestrial urban communities.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {113-116}, doi = {10.1038/s41586-018-0140-0}, pmid = {29795350}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/*physiology ; Biodiversity ; Body Size/*physiology ; Climate ; *Ecosystem ; *Hot Temperature ; *Urbanization ; }, abstract = {Body size is intrinsically linked to metabolic rate and life-history traits, and is a crucial determinant of food webs and community dynamics1,2. The increased temperatures associated with the urban-heat-island effect result in increased metabolic costs and are expected to drive shifts to smaller body sizes 3 . Urban environments are, however, also characterized by substantial habitat fragmentation 4 , which favours mobile species. Here, using a replicated, spatially nested sampling design across ten animal taxonomic groups, we show that urban communities generally consist of smaller species. In addition, although we show urban warming for three habitat types and associated reduced community-weighted mean body sizes for four taxa, three taxa display a shift to larger species along the urbanization gradients. Our results show that the general trend towards smaller-sized species is overruled by filtering for larger species when there is positive covariation between size and dispersal, a process that can mitigate the low connectivity of ecological resources in urban settings 5 . We thus demonstrate that the urban-heat-island effect and urban habitat fragmentation are associated with contrasting community-level shifts in body size that critically depend on the association between body size and dispersal. Because body size determines the structure and dynamics of ecological networks 1 , such shifts may affect urban ecosystem function.}, } @article {pmid29795349, year = {2018}, author = {Lien, AD and Scanziani, M}, title = {Cortical direction selectivity emerges at convergence of thalamic synapses.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {80-86}, doi = {10.1038/s41586-018-0148-5}, pmid = {29795349}, issn = {1476-4687}, support = {P30 EY002162/EY/NEI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Female ; Male ; Mice ; Motion ; Neurons/physiology ; Photic Stimulation ; Synapses/*physiology ; Thalamus/*cytology/*physiology ; Time Factors ; Visual Cortex/*cytology/*physiology ; }, abstract = {Detecting the direction of motion of an object is essential for our representation of the visual environment. The visual cortex is one of the main stages in the mammalian nervous system in which the direction of motion may be computed de novo. Experiments and theories indicate that cortical neurons respond selectively to motion direction by combining inputs that provide information about distinct spatial locations with distinct time delays. Despite the importance of this spatiotemporal offset for direction selectivity, its origin and cellular mechanisms are not fully understood. We show that approximately 80 ± 10 thalamic neurons, which respond with distinct time courses to stimuli in distinct locations, excite mouse visual cortical neurons during visual stimulation. The integration of thalamic inputs with the appropriate spatiotemporal offset provides cortical neurons with a primordial bias for direction selectivity. These data show how cortical neurons selectively combine the spatiotemporal response diversity of thalamic neurons to extract fundamental features of the visual world.}, } @article {pmid29795348, year = {2018}, author = {Martyn, I and Kanno, TY and Ruzo, A and Siggia, ED and Brivanlou, AH}, title = {Self-organization of a human organizer by combined Wnt and Nodal signalling.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {132-135}, pmid = {29795348}, issn = {1476-4687}, support = {R01 GM101653/GM/NIGMS NIH HHS/United States ; R01 HD080699/HD/NICHD NIH HHS/United States ; }, mesh = {Activins/metabolism ; Animals ; Bone Morphogenetic Protein 4/metabolism ; Cell Line ; Chick Embryo ; Epithelial-Mesenchymal Transition ; Goosecoid Protein/metabolism ; Human Embryonic Stem Cells/cytology/metabolism ; Humans ; Mice ; Nerve Tissue/cytology/embryology/metabolism ; Nodal Protein/*metabolism ; Organizers, Embryonic/cytology/*embryology/*metabolism ; Primitive Streak/cytology/metabolism ; Wnt Proteins/*metabolism ; *Wnt Signaling Pathway ; }, abstract = {In amniotes, the development of the primitive streak and its accompanying 'organizer' define the first stages of gastrulation. Although these structures have been characterized in detail in model organisms, the human primitive streak and organizer remain a mystery. When stimulated with BMP4, micropatterned colonies of human embryonic stem cells self-organize to generate early embryonic germ layers 1 . Here we show that, in the same type of colonies, Wnt signalling is sufficient to induce a primitive streak, and stimulation with Wnt and Activin is sufficient to induce an organizer, as characterized by embryo-like sharp boundary formation, markers of epithelial-to-mesenchymal transition and expression of the organizer-specific transcription factor GSC. Moreover, when grafted into chick embryos, human stem cell colonies treated with Wnt and Activin induce and contribute autonomously to a secondary axis while inducing a neural fate in the host. This fulfils the most stringent functional criteria for an organizer, and its discovery represents a milestone in human embryology.}, } @article {pmid29795347, year = {2018}, author = {Kalayil, S and Bhogaraju, S and Bonn, F and Shin, D and Liu, Y and Gan, N and Basquin, J and Grumati, P and Luo, ZQ and Dikic, I}, title = {Insights into catalysis and function of phosphoribosyl-linked serine ubiquitination.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {734-738}, pmid = {29795347}, issn = {1476-4687}, support = {R01 AI127465/AI/NIAID NIH HHS/United States ; }, mesh = {ADP Ribose Transferases/chemistry/metabolism ; Adenosine Diphosphate/metabolism ; Amino Acid Sequence ; Binding Sites ; *Biocatalysis ; Catalytic Domain ; Crystallography, X-Ray ; Legionella pneumophila/*enzymology/genetics/pathogenicity ; Legionnaires' Disease/microbiology ; Membrane Proteins/*chemistry/genetics/*metabolism ; Models, Molecular ; Phosphoric Diester Hydrolases/chemistry/metabolism ; Protein Structure, Secondary ; Serine/*metabolism ; Substrate Specificity ; Ubiquitin/metabolism ; *Ubiquitination ; }, abstract = {Conventional ubiquitination regulates key cellular processes by catalysing the ATP-dependent formation of an isopeptide bond between ubiquitin (Ub) and primary amines in substrate proteins 1 . Recently, the SidE family of bacterial effector proteins (SdeA, SdeB, SdeC and SidE) from pathogenic Legionella pneumophila were shown to use NAD+ to mediate phosphoribosyl-linked ubiquitination of serine residues in host proteins2, 3. However, the molecular architecture of the catalytic platform that enables this complex multistep process remains unknown. Here we describe the structure of the catalytic core of SdeA, comprising mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains, and shed light on the activity of two distinct catalytic sites for serine ubiquitination. The mART catalytic site is composed of an α-helical lobe (AHL) that, together with the mART core, creates a chamber for NAD+ binding and ADP-ribosylation of ubiquitin. The catalytic site in the PDE domain cleaves ADP-ribosylated ubiquitin to phosphoribosyl ubiquitin (PR-Ub) and mediates a two-step PR-Ub transfer reaction: first to a catalytic histidine 277 (forming a transient SdeA H277-PR-Ub intermediate) and subsequently to a serine residue in host proteins. Structural analysis revealed a substrate binding cleft in the PDE domain, juxtaposed with the catalytic site, that is essential for positioning serines for ubiquitination. Using degenerate substrate peptides and newly identified ubiquitination sites in RTN4B, we show that disordered polypeptides with hydrophobic residues surrounding the target serine residues are preferred substrates for SdeA ubiquitination. Infection studies with L. pneumophila expressing substrate-binding mutants of SdeA revealed that substrate ubiquitination, rather than modification of the cellular ubiquitin pool, determines the pathophysiological effect of SdeA during acute bacterial infection.}, } @article {pmid29795346, year = {2018}, author = {Akturk, A and Wasilko, DJ and Wu, X and Liu, Y and Zhang, Y and Qiu, J and Luo, ZQ and Reiter, KH and Brzovic, PS and Klevit, RE and Mao, Y}, title = {Mechanism of phosphoribosyl-ubiquitination mediated by a single Legionella effector.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {729-733}, pmid = {29795346}, issn = {1476-4687}, support = {R01 AI127465/AI/NIAID NIH HHS/United States ; 1R01GM098503-05/NH/NIH HHS/United States ; F32 GM120797/GM/NIGMS NIH HHS/United States ; 1 F32 GM120797/NH/NIH HHS/United States ; P41 GM103485/GM/NIGMS NIH HHS/United States ; R01 GM116964/GM/NIGMS NIH HHS/United States ; R01 GM098503/GM/NIGMS NIH HHS/United States ; R01 GM088055/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; }, mesh = {ADP Ribose Transferases/chemistry/genetics/*metabolism ; Adenosine Diphosphate/metabolism ; Bacterial Proteins/chemistry/genetics/metabolism ; Crystallography, X-Ray ; Legionella pneumophila/*enzymology/genetics ; Lysine/metabolism ; Membrane Proteins/*chemistry/genetics/*metabolism ; Models, Molecular ; Phosphoric Diester Hydrolases/chemistry/genetics/*metabolism ; Protein Domains ; Protein Processing, Post-Translational ; Serine/metabolism ; Ubiquitin/chemistry/metabolism ; *Ubiquitination ; }, abstract = {Ubiquitination is a post-translational modification that regulates many cellular processes in eukaryotes1-4. The conventional ubiquitination cascade culminates in a covalent linkage between the C terminus of ubiquitin (Ub) and a target protein, usually on a lysine side chain1,5. Recent studies of the Legionella pneumophila SidE family of effector proteins revealed a ubiquitination method in which a phosphoribosyl ubiquitin (PR-Ub) is conjugated to a serine residue on substrates via a phosphodiester bond6-8. Here we present the crystal structure of a fragment of the SidE family member SdeA that retains ubiquitination activity, and determine the mechanism of this unique post-translational modification. The structure reveals that the catalytic module contains two distinct functional units: a phosphodiesterase domain and a mono-ADP-ribosyltransferase domain. Biochemical analysis shows that the mono-ADP-ribosyltransferase domain-mediated conversion of Ub to ADP-ribosylated Ub (ADPR-Ub) and the phosphodiesterase domain-mediated ligation of PR-Ub to substrates are two independent activities of SdeA. Furthermore, we present two crystal structures of a homologous phosphodiesterase domain from the SidE family member SdeD 9 in complexes with Ub and ADPR-Ub. The structures suggest a mechanism for how SdeA processes ADPR-Ub to PR-Ub and AMP, and conjugates PR-Ub to a serine residue in substrates. Our study establishes the molecular mechanism of phosphoribosyl-linked ubiquitination and will enable future studies of this unusual type of ubiquitination in eukaryotes.}, } @article {pmid29795345, year = {2018}, author = {Kardol, P and Fanin, N and Wardle, DA}, title = {Long-term effects of species loss on community properties across contrasting ecosystems.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {710-713}, doi = {10.1038/s41586-018-0138-7}, pmid = {29795345}, issn = {1476-4687}, mesh = {*Biodiversity ; Biomass ; *Forests ; *Islands ; *Lakes ; Plants/*classification ; Soil/chemistry ; Sweden ; Time Factors ; }, abstract = {Biodiversity loss can heavily affect the functioning of ecosystems, and improving our understanding of how ecosystems respond to biodiversity decline is one of the main challenges in ecology1-4. Several important aspects of the longer-term effects of biodiversity loss on ecosystems remain unresolved, including how these effects depend on environmental context5-7. Here we analyse data from an across-ecosystem biodiversity manipulation experiment that, to our knowledge, represents the world's longest-running experiment of this type. This experiment has been set up on 30 lake islands in Sweden that vary considerably in productivity and soil fertility owing to differences in fire history8,9. We tested the effects of environmental context on how plant species loss affected two fundamental community attributes-plant community biomass and temporal variability-over 20 years. In contrast to findings from artificially assembled communities10-12, we found that the effects of species loss on community biomass decreased over time; this decrease was strongest on the least productive and least fertile islands. Species loss generally also increased temporal variability, and these effects were greatest on the most productive and most fertile islands. Our findings highlight that the ecosystem-level consequences of biodiversity loss are not constant across ecosystems and that understanding and forecasting these consequences necessitates taking into account the overarching role of environmental context.}, } @article {pmid29795344, year = {2018}, author = {Baghdadi, MB and Castel, D and Machado, L and Fukada, SI and Birk, DE and Relaix, F and Tajbakhsh, S and Mourikis, P}, title = {Reciprocal signalling by Notch-Collagen V-CALCR retains muscle stem cells in their niche.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {714-718}, pmid = {29795344}, issn = {1476-4687}, mesh = {Animals ; Calcitonin Receptor-Like Protein/*metabolism ; Cell Differentiation ; Cell Proliferation ; Cell Self Renewal ; Collagen/genetics/*metabolism ; Gene Expression Regulation ; Immunoglobulin J Recombination Signal Sequence-Binding Protein/metabolism ; Mice ; Muscle, Skeletal/*cytology ; Receptors, Notch/*metabolism ; Satellite Cells, Skeletal Muscle/*cytology/*metabolism ; *Signal Transduction ; *Stem Cell Niche ; Transcription, Genetic ; }, abstract = {The cell microenvironment, which is critical for stem cell maintenance, contains both cellular and non-cellular components, including secreted growth factors and the extracellular matrix1-3. Although Notch and other signalling pathways have previously been reported to regulate quiescence of stem cells4-9, the composition and source of molecules that maintain the stem cell niche remain largely unknown. Here we show that adult muscle satellite (stem) cells in mice produce extracellular matrix collagens to maintain quiescence in a cell-autonomous manner. Using chromatin immunoprecipitation followed by sequencing, we identified NOTCH1/RBPJ-bound regulatory elements adjacent to specific collagen genes, the expression of which is deregulated in Notch-mutant mice. Moreover, we show that Collagen V (COLV) produced by satellite cells is a critical component of the quiescent niche, as depletion of COLV by conditional deletion of the Col5a1 gene leads to anomalous cell cycle entry and gradual diminution of the stem cell pool. Notably, the interaction of COLV with satellite cells is mediated by the Calcitonin receptor, for which COLV acts as a surrogate local ligand. Systemic administration of a calcitonin derivative is sufficient to rescue the quiescence and self-renewal defects found in COLV-null satellite cells. This study reveals a Notch-COLV-Calcitonin receptor signalling cascade that maintains satellite cells in a quiescent state in a cell-autonomous fashion, and raises the possibility that similar reciprocal mechanisms act in diverse stem cell populations.}, } @article {pmid29795343, year = {2018}, author = {Huttenlocker, AK and Grossnickle, DM and Kirkland, JI and Schultz, JA and Luo, ZX}, title = {Late-surviving stem mammal links the lowermost Cretaceous of North America and Gondwana.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {108-112}, doi = {10.1038/s41586-018-0126-y}, pmid = {29795343}, issn = {1476-4687}, mesh = {Animals ; Brain/anatomy & histology ; Dentition ; *Fossils ; *Geographic Mapping ; Mammals/*anatomy & histology/*classification ; North America ; *Phylogeny ; Skull/anatomy & histology ; }, abstract = {Haramiyida was a successful clade of mammaliaforms, spanning the Late Triassic period to at least the Late Jurassic period, but their fossils are scant outside Eurasia and Cretaceous records are controversial1-4. Here we report, to our knowledge, the first cranium of a large haramiyidan from the basal Cretaceous of North America. This cranium possesses an amalgam of stem mammaliaform plesiomorphies and crown mammalian apomorphies. Moreover, it shows dental traits that are diagnostic of isolated teeth of supposed multituberculate affinities from the Cretaceous of Morocco, which have been assigned to the enigmatic 'Hahnodontidae'. Exceptional preservation of this specimen also provides insights into the evolution of the ancestral mammalian brain. We demonstrate the haramiyidan affinities of Gondwanan hahnodontid teeth, removing them from multituberculates, and suggest that hahnodontid mammaliaforms had a much wider, possibly Pangaean distribution during the Jurassic-Cretaceous transition.}, } @article {pmid29795342, year = {2018}, author = {Dong, Y and Mu, Y and Xie, Y and Zhang, Y and Han, Y and Zhou, Y and Wang, W and Liu, Z and Wu, M and Wang, H and Pan, M and Xu, N and Xu, CQ and Yang, M and Fan, S and Deng, H and Tan, T and Liu, X and Liu, L and Li, J and Wang, J and Fang, X and Feng, Y}, title = {Structural basis of ubiquitin modification by the Legionella effector SdeA.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {674-678}, doi = {10.1038/s41586-018-0146-7}, pmid = {29795342}, issn = {1476-4687}, mesh = {ADP Ribose Transferases/chemistry/metabolism ; Arginine/metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Legionella pneumophila/*enzymology ; Membrane Proteins/*chemistry/*metabolism ; Models, Molecular ; Molecular Chaperones/metabolism ; NAD/metabolism ; Phosphoric Diester Hydrolases/chemistry/metabolism ; Protein Processing, Post-Translational ; Substrate Specificity ; Ubiquitin/chemistry/*metabolism ; *Ubiquitination ; }, abstract = {Protein ubiquitination is a multifaceted post-translational modification that controls almost every process in eukaryotic cells. Recently, the Legionella effector SdeA was reported to mediate a unique phosphoribosyl-linked ubiquitination through successive modifications of the Arg42 of ubiquitin (Ub) by its mono-ADP-ribosyltransferase (mART) and phosphodiesterase (PDE) domains. However, the mechanisms of SdeA-mediated Ub modification and phosphoribosyl-linked ubiquitination remain unknown. Here we report the structures of SdeA in its ligand-free, Ub-bound and Ub-NADH-bound states. The structures reveal that the mART and PDE domains of SdeA form a catalytic domain over its C-terminal region. Upon Ub binding, the canonical ADP-ribosyltransferase toxin turn-turn (ARTT) and phosphate-nicotinamide (PN) loops in the mART domain of SdeA undergo marked conformational changes. The Ub Arg72 might act as a 'probe' that interacts with the mART domain first, and then movements may occur in the side chains of Arg72 and Arg42 during the ADP-ribosylation of Ub. Our study reveals the mechanism of SdeA-mediated Ub modification and provides a framework for further investigations into the phosphoribosyl-linked ubiquitination process.}, } @article {pmid29795341, year = {2018}, author = {Xu, Y and Wang, Q and Shen, C and Lin, Q and Wang, P and Lu, M}, title = {Author Correction: A series of energetic metal pentazolate hydrates.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {E5}, doi = {10.1038/s41586-018-0142-y}, pmid = {29795341}, issn = {1476-4687}, abstract = {In this Letter, under Methods section '[Na(H2O)(N5)]⋅2H2O (2)', the description "the intermediate product arylpentazole (5.000 g, 26.18 mmol)" should have read "the intermediate product sodium salt of arylpentazole (5.000 g, 21.64 mmol)". In the legend of Fig. 3, we add that "All temperature points in the stability study were onset temperatures." to avoid misunderstanding. These corrections have been made online.}, } @article {pmid29795340, year = {2018}, author = {Nowoshilow, S and Schloissnig, S and Fei, JF and Dahl, A and Pang, AWC and Pippel, M and Winkler, S and Hastie, AR and Young, G and Roscito, JG and Falcon, F and Knapp, D and Powell, S and Cruz, A and Cao, H and Habermann, B and Hiller, M and Tanaka, EM and Myers, EW}, title = {Author Correction: The axolotl genome and the evolution of key tissue formation regulators.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {E2}, doi = {10.1038/s41586-018-0141-z}, pmid = {29795340}, issn = {1476-4687}, abstract = {In the originally published version of this Article, the sequenced axolotl strain (the homozygous white mutant) was denoted as 'D/D' rather than 'd/d' in Fig. 1a and the accompanying legend, the main text and the Methods section. The original Article has been corrected online.}, } @article {pmid29795328, year = {2018}, author = {Knight, R and Vrbanac, A and Taylor, BC and Aksenov, A and Callewaert, C and Debelius, J and Gonzalez, A and Kosciolek, T and McCall, LI and McDonald, D and Melnik, AV and Morton, JT and Navas, J and Quinn, RA and Sanders, JG and Swafford, AD and Thompson, LR and Tripathi, A and Xu, ZZ and Zaneveld, JR and Zhu, Q and Caporaso, JG and Dorrestein, PC}, title = {Best practices for analysing microbiomes.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {410-422}, doi = {10.1038/s41579-018-0029-9}, pmid = {29795328}, issn = {1740-1534}, abstract = {Complex microbial communities shape the dynamics of various environments, ranging from the mammalian gastrointestinal tract to the soil. Advances in DNA sequencing technologies and data analysis have provided drastic improvements in microbiome analyses, for example, in taxonomic resolution, false discovery rate control and other properties, over earlier methods. In this Review, we discuss the best practices for performing a microbiome study, including experimental design, choice of molecular analysis technology, methods for data analysis and the integration of multiple omics data sets. We focus on recent findings that suggest that operational taxonomic unit-based analyses should be replaced with new methods that are based on exact sequence variants, methods for integrating metagenomic and metabolomic data, and issues surrounding compositional data analysis, where advances have been particularly rapid. We note that although some of these approaches are new, it is important to keep sight of the classic issues that arise during experimental design and relate to research reproducibility. We describe how keeping these issues in mind allows researchers to obtain more insight from their microbiome data sets.}, } @article {pmid29795327, year = {2018}, author = {Du Toit, A}, title = {Silent regulators.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {394-395}, doi = {10.1038/s41579-018-0035-y}, pmid = {29795327}, issn = {1740-1534}, } @article {pmid29795260, year = {2018}, author = {}, title = {Telescope pact, volcano explosion and migraine drug.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {472-473}, doi = {10.1038/d41586-018-05209-7}, pmid = {29795260}, issn = {1476-4687}, } @article {pmid29795259, year = {2018}, author = {Leeming, J}, title = {Hong Kong builds a science-based future.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {S31-S33}, doi = {10.1038/d41586-018-05213-x}, pmid = {29795259}, issn = {1476-4687}, mesh = {Cooperative Behavior ; Hong Kong ; Investments ; Science/economics/*organization & administration/*trends ; }, } @article {pmid29795257, year = {2018}, author = {Guglielmi, G}, title = {How gut microbes are joining the fight against cancer.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {482-484}, doi = {10.1038/d41586-018-05208-8}, pmid = {29795257}, issn = {1476-4687}, mesh = {Animals ; Bacteroides fragilis/immunology ; Clinical Trials as Topic ; Feces/microbiology ; Gastrointestinal Microbiome/*drug effects/immunology ; Humans ; Immunotherapy/*methods ; Mice ; Neoplasms/*drug therapy/immunology/*microbiology ; Skin Neoplasms/drug therapy/immunology/microbiology ; Specific Pathogen-Free Organisms ; }, } @article {pmid29795256, year = {2018}, author = {Vazifeh, MM and Santi, P and Resta, G and Strogatz, SH and Ratti, C}, title = {Addressing the minimum fleet problem in on-demand urban mobility.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {534-538}, doi = {10.1038/s41586-018-0095-1}, pmid = {29795256}, issn = {1476-4687}, mesh = {Automobile Driving/*statistics & numerical data ; Computer Simulation ; *Efficiency, Organizational ; Motor Vehicles/*statistics & numerical data ; New York City ; *Social Environment ; *Urban Population ; }, abstract = {Information and communication technologies have opened the way to new solutions for urban mobility that provide better ways to match individuals with on-demand vehicles. However, a fundamental unsolved problem is how best to size and operate a fleet of vehicles, given a certain demand for personal mobility. Previous studies1-5 either do not provide a scalable solution or require changes in human attitudes towards mobility. Here we provide a network-based solution to the following 'minimum fleet problem', given a collection of trips (specified by origin, destination and start time), of how to determine the minimum number of vehicles needed to serve all the trips without incurring any delay to the passengers. By introducing the notion of a 'vehicle-sharing network', we present an optimal computationally efficient solution to the problem, as well as a nearly optimal solution amenable to real-time implementation. We test both solutions on a dataset of 150 million taxi trips taken in the city of New York over one year 6 . The real-time implementation of the method with near-optimal service levels allows a 30 per cent reduction in fleet size compared to current taxi operation. Although constraints on driver availability and the existence of abnormal trip demands may lead to a relatively larger optimal value for the fleet size than that predicted here, the fleet size remains robust for a wide range of variations in historical trip demand. These predicted reductions in fleet size follow directly from a reorganization of taxi dispatching that could be implemented with a simple urban app; they do not assume ride sharing7-9, nor require changes to regulations, business models, or human attitudes towards mobility to become effective. Our results could become even more relevant in the years ahead as fleets of networked, self-driving cars become commonplace10-14.}, } @article {pmid29795255, year = {2018}, author = {Ni, GX and McLeod, AS and Sun, Z and Wang, L and Xiong, L and Post, KW and Sunku, SS and Jiang, BY and Hone, J and Dean, CR and Fogler, MM and Basov, DN}, title = {Fundamental limits to graphene plasmonics.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {530-533}, doi = {10.1038/s41586-018-0136-9}, pmid = {29795255}, issn = {1476-4687}, abstract = {Plasmon polaritons are hybrid excitations of light and mobile electrons that can confine the energy of long-wavelength radiation at the nanoscale. Plasmon polaritons may enable many enigmatic quantum effects, including lasing 1 , topological protection2,3 and dipole-forbidden absorption 4 . A necessary condition for realizing such phenomena is a long plasmonic lifetime, which is notoriously difficult to achieve for highly confined modes 5 . Plasmon polaritons in graphene-hybrids of Dirac quasiparticles and infrared photons-provide a platform for exploring light-matter interaction at the nanoscale6,7. However, plasmonic dissipation in graphene is substantial 8 and its fundamental limits remain undetermined. Here we use nanometre-scale infrared imaging to investigate propagating plasmon polaritons in high-mobility encapsulated graphene at cryogenic temperatures. In this regime, the propagation of plasmon polaritons is primarily restricted by the dielectric losses of the encapsulated layers, with a minor contribution from electron-phonon interactions. At liquid-nitrogen temperatures, the intrinsic plasmonic propagation length can exceed 10 micrometres, or 50 plasmonic wavelengths, thus setting a record for highly confined and tunable polariton modes. Our nanoscale imaging results reveal the physics of plasmonic dissipation and will be instrumental in mitigating such losses in heterostructure engineering applications.}, } @article {pmid29795254, year = {2018}, author = {González-Forero, M and Gardner, A}, title = {Inference of ecological and social drivers of human brain-size evolution.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {554-557}, doi = {10.1038/s41586-018-0127-x}, pmid = {29795254}, issn = {1476-4687}, mesh = {Adult ; Animals ; *Biological Evolution ; Body Size ; Brain/*anatomy & histology/*metabolism ; Competitive Behavior ; Cooperative Behavior ; *Ecology ; Female ; Humans ; Models, Biological ; Organ Size/*physiology ; *Social Behavior ; }, abstract = {The human brain is unusually large. It has tripled in size from Australopithecines to modern humans 1 and has become almost six times larger than expected for a placental mammal of human size 2 . Brains incur high metabolic costs 3 and accordingly a long-standing question is why the large human brain has evolved 4 . The leading hypotheses propose benefits of improved cognition for overcoming ecological5-7, social8-10 or cultural11-14 challenges. However, these hypotheses are typically assessed using correlative analyses, and establishing causes for brain-size evolution remains difficult15,16. Here we introduce a metabolic approach that enables causal assessment of social hypotheses for brain-size evolution. Our approach yields quantitative predictions for brain and body size from formalized social hypotheses given empirical estimates of the metabolic costs of the brain. Our model predicts the evolution of adult Homo sapiens-sized brains and bodies when individuals face a combination of 60% ecological, 30% cooperative and 10% between-group competitive challenges, and suggests that between-individual competition has been unimportant for driving human brain-size evolution. Moreover, our model indicates that brain expansion in Homo was driven by ecological rather than social challenges, and was perhaps strongly promoted by culture. Our metabolic approach thus enables causal assessments that refine, refute and unify hypotheses of brain-size evolution.}, } @article {pmid29795253, year = {2018}, author = {Main, R and Yang, IS and Chan, V and Li, D and Lin, FX and Mahajan, N and Pen, UL and Vanderlinde, K and van Kerkwijk, MH}, title = {Pulsar emission amplified and resolved by plasma lensing in an eclipsing binary.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {522-525}, doi = {10.1038/s41586-018-0133-z}, pmid = {29795253}, issn = {1476-4687}, abstract = {Radio pulsars scintillate because their emission travels through the ionized interstellar medium along multiple paths, which interfere with each other. It has long been realized that, independent of their nature, the regions responsible for the scintillation could be used as 'interstellar lenses' to localize pulsar emission regions1,2. Most such lenses, however, resolve emission components only marginally, limiting results to statistical inferences and detections of small positional shifts3-5. As lenses situated close to their source offer better resolution, it should be easier to resolve emission regions of pulsars located in high-density environments such as supernova remnants 6 or binaries in which the pulsar's companion has an ionized outflow. Here we report observations of extreme plasma lensing in the 'black widow' pulsar, B1957+20, near the phase in its 9.2-hour orbit at which its emission is eclipsed by its companion's outflow7-9. During the lensing events, the observed radio flux is enhanced by factors of up to 70-80 at specific frequencies. The strongest events clearly resolve the emission regions: they affect the narrow main pulse and parts of the wider interpulse differently. We show that the events arise naturally from density fluctuations in the outer regions of the outflow, and we infer a resolution of our lenses that is comparable to the pulsar's radius, about 10 kilometres. Furthermore, the distinct frequency structures imparted by the lensing are reminiscent of what is observed for the repeating fast radio burst FRB 121102, providing observational support for the idea that this source is observed through, and thus at times strongly magnified by, plasma lenses 10 .}, } @article {pmid29795252, year = {2018}, author = {Bindeman, IN and Zakharov, DO and Palandri, J and Greber, ND and Dauphas, N and Retallack, GJ and Hofmann, A and Lackey, JS and Bekker, A}, title = {Rapid emergence of subaerial landmasses and onset of a modern hydrologic cycle 2.5 billion years ago.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {545-548}, doi = {10.1038/s41586-018-0131-1}, pmid = {29795252}, issn = {1476-4687}, mesh = {*Earth (Planet) ; Geologic Sediments/*analysis/*chemistry ; History, Ancient ; Minerals/analysis/chemistry ; Oxygen Isotopes/analysis ; Seawater/chemistry ; Temperature ; Water/*chemistry ; *Water Cycle ; }, abstract = {The history of the growth of continental crust is uncertain, and several different models that involve a gradual, decelerating, or stepwise process have been proposed1-4. Even more uncertain is the timing and the secular trend of the emergence of most landmasses above the sea (subaerial landmasses), with estimates ranging from about one billion to three billion years ago5-7. The area of emerged crust influences global climate feedbacks and the supply of nutrients to the oceans 8 , and therefore connects Earth's crustal evolution to surface environmental conditions9-11. Here we use the triple-oxygen-isotope composition of shales from all continents, spanning 3.7 billion years, to provide constraints on the emergence of continents over time. Our measurements show a stepwise total decrease of 0.08 per mille in the average triple-oxygen-isotope value of shales across the Archaean-Proterozoic boundary. We suggest that our data are best explained by a shift in the nature of water-rock interactions, from near-coastal in the Archaean era to predominantly continental in the Proterozoic, accompanied by a decrease in average surface temperatures. We propose that this shift may have coincided with the onset of a modern hydrological cycle owing to the rapid emergence of continental crust with near-modern average elevation and aerial extent roughly 2.5 billion years ago.}, } @article {pmid29795251, year = {2018}, author = {Burke, M and Davis, WM and Diffenbaugh, NS}, title = {Large potential reduction in economic damages under UN mitigation targets.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {549-553}, doi = {10.1038/s41586-018-0071-9}, pmid = {29795251}, issn = {1476-4687}, abstract = {International climate change agreements typically specify global warming thresholds as policy targets 1 , but the relative economic benefits of achieving these temperature targets remain poorly understood2,3. Uncertainties include the spatial pattern of temperature change, how global and regional economic output will respond to these changes in temperature, and the willingness of societies to trade present for future consumption. Here we combine historical evidence 4 with national-level climate 5 and socioeconomic 6 projections to quantify the economic damages associated with the United Nations (UN) targets of 1.5 °C and 2 °C global warming, and those associated with current UN national-level mitigation commitments (which together approach 3 °C warming 7). We find that by the end of this century, there is a more than 75% chance that limiting warming to 1.5 °C would reduce economic damages relative to 2 °C, and a more than 60% chance that the accumulated global benefits will exceed US$20 trillion under a 3% discount rate (2010 US dollars). We also estimate that 71% of countries-representing 90% of the global population-have a more than 75% chance of experiencing reduced economic damages at 1.5 °C, with poorer countries benefiting most. Our results could understate the benefits of limiting warming to 1.5 °C if unprecedented extreme outcomes, such as large-scale sea level rise 8 , occur for warming of 2 °C but not for warming of 1.5 °C. Inclusion of other unquantified sources of uncertainty, such as uncertainty in secular growth rates beyond that contained in existing socioeconomic scenarios, could also result in less precise impact estimates. We find considerably greater reductions in global economic output beyond 2 °C. Relative to a world that did not warm beyond 2000-2010 levels, we project 15%-25% reductions in per capita output by 2100 for the 2.5-3 °C of global warming implied by current national commitments 7 , and reductions of more than 30% for 4 °C warming. Our results therefore suggest that achieving the 1.5 °C target is likely to reduce aggregate damages and lessen global inequality, and that failing to meet the 2 °C target is likely to increase economic damages substantially.}, } @article {pmid29795126, year = {2018}, author = {Koch, L}, title = {Estimating heritability without genetic testing.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {403}, doi = {10.1038/s41576-018-0021-2}, pmid = {29795126}, issn = {1471-0064}, } @article {pmid29795125, year = {2018}, author = {Uszczynska-Ratajczak, B and Lagarde, J and Frankish, A and Guigó, R and Johnson, R}, title = {Towards a complete map of the human long non-coding RNA transcriptome.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {535-548}, doi = {10.1038/s41576-018-0017-y}, pmid = {29795125}, issn = {1471-0064}, abstract = {Gene maps, or annotations, enable us to navigate the functional landscape of our genome. They are a resource upon which virtually all studies depend, from single-gene to genome-wide scales and from basic molecular biology to medical genetics. Yet present-day annotations suffer from trade-offs between quality and size, with serious but often unappreciated consequences for downstream studies. This is particularly true for long non-coding RNAs (lncRNAs), which are poorly characterized compared to protein-coding genes. Long-read sequencing technologies promise to improve current annotations, paving the way towards a complete annotation of lncRNAs expressed throughout a human lifetime.}, } @article {pmid29794223, year = {2018}, author = {Hinnov, LA}, title = {Astronomical metronome of geological consequence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6104-6106}, pmid = {29794223}, issn = {1091-6490}, mesh = {Astronomical Phenomena ; *Astronomy ; Extraterrestrial Environment ; Geological Phenomena ; *Geology ; }, } @article {pmid29794222, year = {2018}, author = {DeLoughery, A and Lalanne, JB and Losick, R and Li, GW}, title = {Maturation of polycistronic mRNAs by the endoribonuclease RNase Y and its associated Y-complex in Bacillus subtilis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5585-E5594}, doi = {10.1073/pnas.1803283115}, pmid = {29794222}, issn = {1091-6490}, support = {R00 GM105913/GM/NIGMS NIH HHS/United States ; R01 GM018568/GM/NIGMS NIH HHS/United States ; R35 GM124732/GM/NIGMS NIH HHS/United States ; R37 GM018568/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bacillus subtilis/*metabolism ; Bacterial Proteins/metabolism ; Endoribonucleases/*metabolism ; Gene Expression Regulation, Bacterial/physiology ; Operon/physiology ; RNA Processing, Post-Transcriptional/physiology ; RNA, Messenger/*metabolism ; RNA, Untranslated/metabolism ; Ribonucleases/*metabolism ; Staphylococcus aureus/metabolism ; Transcriptome/physiology ; }, abstract = {Endonucleolytic cleavage within polycistronic mRNAs can lead to differential stability, and thus discordant abundance, among cotranscribed genes. RNase Y, the major endonuclease for mRNA decay in Bacillus subtilis, was originally identified for its cleavage activity toward the cggR-gapA operon, an event that differentiates the synthesis of a glycolytic enzyme from its transcriptional regulator. A three-protein Y-complex (YlbF, YmcA, and YaaT) was recently identified as also being required for this cleavage in vivo, raising the possibility that it is an accessory factor acting to regulate RNase Y. However, whether the Y-complex is broadly required for RNase Y activity is unknown. Here, we used end-enrichment RNA sequencing (Rend-seq) to globally identify operon mRNAs that undergo maturation posttranscriptionally by RNase Y and the Y-complex. We found that the Y-complex is required for the majority of RNase Y-mediated mRNA maturation events and also affects riboswitch abundance in B. subtilis In contrast, noncoding RNA maturation by RNase Y often does not require the Y-complex. Furthermore, deletion of RNase Y has more pleiotropic effects on the transcriptome and cell growth than deletions of the Y-complex. We propose that the Y-complex is a specificity factor for RNase Y, with evidence that its role is conserved in Staphylococcus aureus.}, } @article {pmid29794221, year = {2018}, author = {Saiki, JP and Cao, H and Van Wassenhove, LD and Viswanathan, V and Bloomstein, J and Nambiar, DK and Mattingly, AJ and Jiang, D and Chen, CH and Stevens, MC and Simmons, AL and Park, HS and von Eyben, R and Kool, ET and Sirjani, D and Knox, SM and Le, QT and Mochly-Rosen, D}, title = {Aldehyde dehydrogenase 3A1 activation prevents radiation-induced xerostomia by protecting salivary stem cells from toxic aldehydes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6279-6284}, pmid = {29794221}, issn = {1091-6490}, support = {P01 CA067166/CA/NCI NIH HHS/United States ; R01 GM110050/GM/NIGMS NIH HHS/United States ; R01 AA011147/AA/NIAAA NIH HHS/United States ; R01 DE025227/DE/NIDCR NIH HHS/United States ; R37 AA011147/AA/NIAAA NIH HHS/United States ; T32 DK098132/DK/NIDDK NIH HHS/United States ; T32 GM008568/GM/NIGMS NIH HHS/United States ; T32 GM089626/GM/NIGMS NIH HHS/United States ; U10 CA180816/CA/NCI NIH HHS/United States ; }, mesh = {Aldehyde Dehydrogenase/*metabolism ; Aldehydes/*metabolism ; Animals ; Apoptosis/drug effects ; Cyclohexenes/*pharmacology ; Female ; Head and Neck Neoplasms/metabolism/radiotherapy ; Limonene ; Medicine, Chinese Traditional/methods ; Mice ; Mice, Inbred C57BL ; Protective Agents/pharmacology ; Radiotherapy/*adverse effects ; Salivary Glands/drug effects/*metabolism/radiation effects ; Stem Cells/drug effects/metabolism ; Submandibular Gland/drug effects/metabolism ; Terpenes/*pharmacology ; Xerostomia/drug therapy/*metabolism ; }, abstract = {Xerostomia (dry mouth) is the most common side effect of radiation therapy in patients with head and neck cancer and causes difficulty speaking and swallowing. Since aldehyde dehydrogenase 3A1 (ALDH3A1) is highly expressed in mouse salivary stem/progenitor cells (SSPCs), we sought to determine the role of ALDH3A1 in SSPCs using genetic loss-of-function and pharmacologic gain-of-function studies. Using DarkZone dye to measure intracellular aldehydes, we observed higher aldehyde accumulation in irradiated Aldh3a1-/- adult murine salisphere cells and in situ in whole murine embryonic salivary glands enriched in SSPCs compared with wild-type glands. To identify a safe ALDH3A1 activator for potential clinical testing, we screened a traditional Chinese medicine library and isolated d-limonene, commonly used as a food-flavoring agent, as a single constituent activator. ALDH3A1 activation by d-limonene significantly reduced aldehyde accumulation in SSPCs and whole embryonic glands, increased sphere-forming ability, decreased apoptosis, and improved submandibular gland structure and function in vivo after radiation. A phase 0 study in patients with salivary gland tumors showed effective delivery of d-limonene into human salivary glands following daily oral dosing. Given its safety and bioavailability, d-limonene may be a good clinical candidate for mitigating xerostomia in patients with head and neck cancer receiving radiation therapy.}, } @article {pmid29794220, year = {2018}, author = {Griesmann, M and Chang, Y and Liu, X and Song, Y and Haberer, G and Crook, MB and Billault-Penneteau, B and Lauressergues, D and Keller, J and Imanishi, L and Roswanjaya, YP and Kohlen, W and Pujic, P and Battenberg, K and Alloisio, N and Liang, Y and Hilhorst, H and Salgado, MG and Hocher, V and Gherbi, H and Svistoonoff, S and Doyle, JJ and He, S and Xu, Y and Xu, S and Qu, J and Gao, Q and Fang, X and Fu, Y and Normand, P and Berry, AM and Wall, LG and Ané, JM and Pawlowski, K and Xu, X and Yang, H and Spannagl, M and Mayer, KFX and Wong, GK and Parniske, M and Delaux, PM and Cheng, S}, title = {Phylogenomics reveals multiple losses of nitrogen-fixing root nodule symbiosis.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {}, doi = {10.1126/science.aat1743}, pmid = {29794220}, issn = {1095-9203}, mesh = {*Bacterial Physiological Phenomena ; Evolution, Molecular ; *Fabaceae/classification/genetics/microbiology ; Genome, Plant ; Genomics ; Nitrogen/*metabolism ; *Nitrogen Fixation ; Phylogeny ; Root Nodules, Plant/*microbiology ; *Symbiosis ; }, abstract = {The root nodule symbiosis of plants with nitrogen-fixing bacteria affects global nitrogen cycles and food production but is restricted to a subset of genera within a single clade of flowering plants. To explore the genetic basis for this scattered occurrence, we sequenced the genomes of 10 plant species covering the diversity of nodule morphotypes, bacterial symbionts, and infection strategies. In a genome-wide comparative analysis of a total of 37 plant species, we discovered signatures of multiple independent loss-of-function events in the indispensable symbiotic regulator NODULE INCEPTION in 10 of 13 genomes of nonnodulating species within this clade. The discovery that multiple independent losses shaped the present-day distribution of nitrogen-fixing root nodule symbiosis in plants reveals a phylogenetically wider distribution in evolutionary history and a so-far-underestimated selection pressure against this symbiosis.}, } @article {pmid29794219, year = {2018}, author = {Bai, R and Wan, R and Yan, C and Lei, J and Shi, Y}, title = {Structures of the fully assembled Saccharomyces cerevisiae spliceosome before activation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1423-1429}, doi = {10.1126/science.aau0325}, pmid = {29794219}, issn = {1095-9203}, mesh = {Amino Acid Sequence ; Cryoelectron Microscopy ; Nucleic Acid Conformation ; Protein Conformation ; RNA Precursors/chemistry/metabolism ; RNA Splice Sites ; RNA, Small Nuclear/chemistry/metabolism ; Ribonucleoprotein, U1 Small Nuclear/chemistry/metabolism ; Saccharomyces cerevisiae/*metabolism/*ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; Spliceosomes/*metabolism/*ultrastructure ; }, abstract = {The precatalytic spliceosome (B complex) is preceded by the pre-B complex. Here we report the cryo-electron microscopy structures of the Saccharomyces cerevisiae pre-B and B complexes at average resolutions of 3.3 to 4.6 and 3.9 angstroms, respectively. In the pre-B complex, the duplex between the 5' splice site (5'SS) and U1 small nuclear RNA (snRNA) is recognized by Yhc1, Luc7, and the Sm ring. In the B complex, U1 small nuclear ribonucleoprotein is dissociated, the 5'-exon-5'SS sequences are translocated near U6 snRNA, and three B-specific proteins may orient the precursor messenger RNA. In both complexes, U6 snRNA is anchored to loop I of U5 snRNA, and the duplex between the branch point sequence and U2 snRNA is recognized by the SF3b complex. Structural analysis reveals the mechanism of assembly and activation for the yeast spliceosome.}, } @article {pmid29794218, year = {2018}, author = {Lin, S and Dikler, S and Blincoe, WD and Ferguson, RD and Sheridan, RP and Peng, Z and Conway, DV and Zawatzky, K and Wang, H and Cernak, T and Davies, IW and DiRocco, DA and Sheng, H and Welch, CJ and Dreher, SD}, title = {Mapping the dark space of chemical reactions with extended nanomole synthesis and MALDI-TOF MS.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6402}, pages = {}, doi = {10.1126/science.aar6236}, pmid = {29794218}, issn = {1095-9203}, abstract = {Understanding the practical limitations of chemical reactions is critically important for efficiently planning the synthesis of compounds in pharmaceutical, agrochemical, and specialty chemical research and development. However, literature reports of the scope of new reactions are often cursory and biased toward successful results, severely limiting the ability to predict reaction outcomes for untested substrates. We herein illustrate strategies for carrying out large-scale surveys of chemical reactivity by using a material-sparing nanomole-scale automated synthesis platform with greatly expanded synthetic scope combined with ultrahigh-throughput matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS).}, } @article {pmid29794217, year = {2018}, author = {Nakamura, N and Huang, CSY}, title = {Atmospheric blocking as a traffic jam in the jet stream.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {42-47}, doi = {10.1126/science.aat0721}, pmid = {29794217}, issn = {1095-9203}, abstract = {Atmospheric blocking due to anomalous, persistent meandering of the jet stream often causes weather extremes in the mid-latitudes. Despite the ubiquity of blocking, the onset mechanism is not well understood. Here we demonstrate a close analogy between blocking and traffic congestion on a highway by using meteorological data and show that blocking and traffic congestion can be described by a common mathematical theory. The theory predicts that the jet stream has a capacity for the flux of wave activity (a measure of meandering), just as the highway has traffic capacity, and when the capacity is exceeded, blocking manifests as congestion. Stationary waves modulate the jet stream's capacity for transient waves and localize block formation. Climate change likely affects blocking frequency by modifying the jet stream's proximity to capacity.}, } @article {pmid29794216, year = {2018}, author = {MacLeod, KG and Quinton, PC and Sepúlveda, J and Negra, MH}, title = {Postimpact earliest Paleogene warming shown by fish debris oxygen isotopes (El Kef, Tunisia).}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {1467-1469}, doi = {10.1126/science.aap8525}, pmid = {29794216}, issn = {1095-9203}, mesh = {Animals ; *Extinction, Biological ; Fishes ; Fossils ; *Global Warming ; *Greenhouse Effect ; Oxygen Isotopes/analysis ; Temperature ; Tunisia ; }, abstract = {Greenhouse warming is a predicted consequence of the Chicxulub impact, but supporting data are sparse. This shortcoming compromises understanding of the impact's effects, and it has persisted due to an absence of sections that both contain suitable material for traditional carbonate- or organic-based paleothermometry and are complete and expanded enough to resolve changes on short time scales. We address the problem by analyzing the oxygen isotopic composition of fish debris, phosphatic microfossils that are relatively resistant to diagenetic alteration, from the Global Stratotype Section and Point for the Cretaceous/Paleogene boundary at El Kef, Tunisia. We report an ~1 per mil decrease in oxygen isotopic values (~5°C warming) beginning at the boundary and spanning ~300 centimeters of section (~100,000 years). The pattern found matches expectations for impact-initiated greenhouse warming.}, } @article {pmid29793941, year = {2018}, author = {Briggs, DEG}, title = {Sampling the insects of the amber forest.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6525-6527}, pmid = {29793941}, issn = {1091-6490}, mesh = {*Amber ; Animals ; Forests ; Fossils ; *Insecta ; Specimen Handling ; }, } @article {pmid29793940, year = {2018}, author = {Fine, PVA and Lohmann, LG}, title = {Importance of dispersal in the assembly of the Neotropical biota.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5829-5831}, pmid = {29793940}, issn = {1091-6490}, mesh = {*Biota ; *Ecosystem ; Prokaryotic Cells ; }, } @article {pmid29793939, year = {2018}, author = {Gerrard, E and Mutt, E and Nagata, T and Koyanagi, M and Flock, T and Lesca, E and Schertler, GFX and Terakita, A and Deupi, X and Lucas, RJ}, title = {Convergent evolution of tertiary structure in rhodopsin visual proteins from vertebrates and box jellyfish.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6201-6206}, doi = {10.1073/pnas.1721333115}, pmid = {29793939}, issn = {1091-6490}, support = {BB/K002252/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Cubozoa/*genetics ; *Evolution, Molecular ; HEK293 Cells ; Humans ; Molecular Dynamics Simulation ; Phylogeny ; Recombinant Proteins/chemistry/genetics/metabolism ; *Rhodopsin/chemistry/genetics/metabolism ; Vision, Ocular/*genetics ; }, abstract = {Box jellyfish and vertebrates are separated by >500 million years of evolution yet have structurally analogous lens eyes that employ rhodopsin photopigments for vision. All opsins possess a negatively charged residue-the counterion-to maintain visible-light sensitivity and facilitate photoisomerization of their retinaldehyde chromophore. In vertebrate rhodopsins, the molecular evolution of the counterion position-from a highly conserved distal location in the second extracellular loop (E181) to a proximal location in the third transmembrane helix (E113)-is established as a key driver of higher fidelity photoreception. Here, we use computational biology and heterologous action spectroscopy to determine whether the appearance of the advanced visual apparatus in box jellyfish was also accompanied by changes in the opsin tertiary structure. We found that the counterion in an opsin from the lens eye of the box jellyfish Carybdea rastonii (JellyOp) has also moved to a unique proximal location within the transmembrane bundle-E94 in TM2. Furthermore, we reveal that this Schiff base/counterion system includes an additional positive charge-R186-that has coevolved with E94 to functionally separate E94 and E181 in the chromophore-binding pocket of JellyOp. By engineering this pocket-neutralizing R186 and E94, or swapping E94 with the vertebrate counterion E113-we can recreate versions of the invertebrate and vertebrate counterion systems, respectively, supporting a relatively similar overall architecture in this region of animal opsins. In summary, our data establish the third only counterion site in animal opsins and reveal convergent evolution of tertiary structure in opsins from distantly related species with advanced visual systems.}, } @article {pmid29793938, year = {2018}, author = {Kurtuldu, G and Shamlaye, KF and Löffler, JF}, title = {Metastable quasicrystal-induced nucleation in a bulk glass-forming liquid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6123-6128}, pmid = {29793938}, issn = {1091-6490}, abstract = {This study presents a unique Mg-based alloy composition in the Mg-Zn-Yb system which exhibits bulk metallic glass, metastable icosahedral quasicrystals (iQCs), and crystalline approximant phases in the as-cast condition. Microscopy revealed a smooth gradual transition from glass to QC. We also report the complete melting of a metastable eutectic phase mixture (including a QC phase), generated via suppression of the metastable-to-stable phase transition at high heating rates using fast differential scanning calorimetry (FDSC). The melting temperature and enthalpy of fusion of this phase mixture could be measured directly, which unambiguously proves its metastability in any temperature range. The kinetic pathway from liquid state to stable solid state (an approximant phase) minimizes the free-energy barrier for nucleation through an intermediate state (metastable QC phase) because of its low solid-liquid interfacial energy. At high undercooling of the liquid, where diffusion is limited, another approximant phase with near-liquid composition forms just above the glass-transition temperature. These experimental results shed light on the competition between metastable and stable crystals, and on glass formation via system frustration associated with the presence of several free-energy minima.}, } @article {pmid29793937, year = {2018}, author = {Segal, NL}, title = {Revisiting sources of left-handedness in multiple-birth individuals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5832-5834}, pmid = {29793937}, issn = {1091-6490}, mesh = {*Birth Weight ; *Functional Laterality ; Humans ; }, } @article {pmid29793936, year = {2018}, author = {Popa, M and Tahir, S and Elrod, J and Kim, SH and Leuschner, F and Kessler, T and Bugert, P and Pohl, U and Wagner, AH and Hecker, M}, title = {Role of CD40 and ADAMTS13 in von Willebrand factor-mediated endothelial cell-platelet-monocyte interaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {E5556-E5565}, pmid = {29793936}, issn = {1091-6490}, mesh = {ADAMTS13 Protein/*metabolism ; Adolescent ; Adult ; Aged ; Animals ; Atherosclerosis/metabolism ; Blood Platelets/*metabolism ; CD40 Antigens/*metabolism ; Cell Communication/*physiology ; Cells, Cultured ; Endothelial Cells/*metabolism ; Endothelium, Vascular/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Monocytes/metabolism ; Platelet Aggregation/physiology ; Stress, Mechanical ; Young Adult ; von Willebrand Factor/*metabolism ; }, abstract = {Monocyte extravasation into the vessel wall is a key step in atherogenesis. It is still elusive how monocytes transmigrate through the endothelial cell (EC) monolayer at atherosclerosis predilection sites. Platelets tethered to ultra-large von Willebrand factor (ULVWF) multimers deposited on the luminal EC surface following CD40 ligand (CD154) stimulation may facilitate monocyte diapedesis. Human ECs grown in a parallel plate flow chamber for live-cell imaging or Transwell permeable supports for transmigration assay were exposed to fluid or orbital shear stress and CD154. Human isolated platelets and/or monocytes were superfused over or added on top of the EC monolayer. Plasma levels and activity of the ULVWF multimer-cleaving protease ADAMTS13 were compared between coronary artery disease (CAD) patients and controls and were verified by the bioassay. Two-photon intravital microscopy was performed to monitor CD154-dependent leukocyte recruitment in the cremaster microcirculation of ADAMTS13-deficient versus wild-type mice. CD154-induced ULVWF multimer-platelet string formation on the EC surface trapped monocytes and facilitated transmigration through the EC monolayer despite high shear stress. Two-photon intravital microscopy revealed CD154-induced ULVWF multimer-platelet string formation preferentially in venules, due to strong EC expression of CD40, causing prominent downstream leukocyte extravasation. Plasma ADAMTS13 abundance and activity were significantly reduced in CAD patients and strongly facilitated both ULVWF multimer-platelet string formation and monocyte trapping in vitro. Moderate ADAMTS13 deficiency in CAD patients augments CD154-mediated deposition of platelet-decorated ULVWF multimers on the luminal EC surface, reinforcing the trapping of circulating monocytes at atherosclerosis predilection sites and promoting their diapedesis.}, } @article {pmid29793935, year = {2018}, author = {Burgess, MG and Gaines, SD}, title = {The scale of life and its lessons for humanity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6328-6330}, pmid = {29793935}, issn = {1091-6490}, mesh = {*Life ; }, } @article {pmid29793827, year = {2018}, author = {Bakaletz, LO and Novotny, LA}, title = {Nontypeable Haemophilus influenzae (NTHi).}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {727-728}, doi = {10.1016/j.tim.2018.05.001}, pmid = {29793827}, issn = {1878-4380}, abstract = {In this infographic the diseases caused by nontypeable Haemophilus influenzae (NTHi), including otitis media, are discussed. Encapsulated type b Haemophilus influenzae (Hib) was responsible for most of the invasive disease (meningitis) prior to the use of Hib vaccines. As Hib vaccines have no effect on infections due to nontypeable H. influenzae (NTHi), in areas where Hib vaccines are used, nontypeable strains are now the most common cause of invasive disease. Moreover, NTHi contributes to the ∼21000 otitis media (OM)-associated deaths per year. Due to this collective global morbidity and mortality, concerted vaccine development is underway. In addition to preventing disease, an effective vaccine will likely help to mitigate the global crisis of antibiotic resistance. Since 1973, ampicillin resistance due to NTHi's production of β-lactamase has been recognized; however, a significant concern is the more recent emergence and spread of β-lactamase-negative-ampicillin-resistant (BLNAR) strains in many regions of the world. As such, H. influenzae is one of 12 bacterial pathogens that are considered priority pathogens by the World Health Organization.}, } @article {pmid29793806, year = {2018}, author = {Simões, ML and Caragata, EP and Dimopoulos, G}, title = {Diverse Host and Restriction Factors Regulate Mosquito-Pathogen Interactions.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {603-616}, doi = {10.1016/j.pt.2018.04.011}, pmid = {29793806}, issn = {1471-5007}, mesh = {Animals ; Culicidae/*parasitology/*virology ; Dengue/transmission/virology ; Dengue Virus/*physiology ; *Host-Parasite Interactions ; Malaria/parasitology/transmission ; Mosquito Vectors/parasitology/virology ; Plasmodium/*physiology ; Zika Virus/*physiology ; Zika Virus Infection/transmission/virology ; }, abstract = {Mosquitoes transmit diseases that seriously impact global human health. Despite extensive knowledge of the life cycles of mosquito-borne parasites and viruses within their hosts, control strategies have proven insufficient to halt their spread. An understanding of the relationships established between such pathogens and the host tissues they inhabit is therefore paramount for the development of new strategies that specifically target these interactions, to prevent the pathogens' maturation and transmission. Here we present an updated account of the antagonists and host factors that affect the development of Plasmodium, the parasite causing malaria, and mosquito-borne viruses, such as dengue virus and Zika virus, within their mosquito vectors, and we discuss the similarities and differences between Plasmodium and viral systems, looking toward the elucidation of new targets for disease control.}, } @article {pmid29793805, year = {2018}, author = {Bartumeus, F and Oltra, A and Palmer, JRB}, title = {Citizen Science: A Gateway for Innovation in Disease-Carrying Mosquito Management?.}, journal = {Trends in parasitology}, volume = {34}, number = {9}, pages = {727-729}, doi = {10.1016/j.pt.2018.04.010}, pmid = {29793805}, issn = {1471-5007}, abstract = {Traditional methods for tracking disease-carrying mosquitoes are hitting budget constraints as the scales over which they must be implemented grow exponentially. Citizen science offers a novel solution to this problem but requires new models of innovation in the public health sector.}, } @article {pmid29793792, year = {2018}, author = {Scott, JE and Campbell, RM and Baj, LM and Burns, MC and Price, MS and Sykes, JD and Vinyard, CJ}, title = {Dietary signals in the premolar dentition of primates.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {221-234}, doi = {10.1016/j.jhevol.2018.04.006}, pmid = {29793792}, issn = {1095-8606}, abstract = {Dietary adaptations specific to the premolar row remain largely undocumented across primates. This study examines how relative premolar size varies among broad dietary groups (i.e., folivores, frugivores, insectivores, hard-object feeders) using a phylogenetically and ecologically diverse sample of species. We quantified relative premolar size with shape ratios computed using mandibular length, body mass, palate area, and M1 area to evaluate hypotheses that link variation in relative premolar size to differences in tooth loading, energy requirements, the probability of tooth-food-tooth contact during mastication, and shifts in preferred bite point. Our results revealed the following dietary signals. First, primate folivores have large premolar rows relative to palate area in comparison to frugivores and insectivores. This contrast is consistent with the hypothesis that folivores require large postcanine teeth relative to the size of the oral cavity to increase the probability of particle fracture during mastication. Second, hard-object feeders are distinct from other groups in having P4s that are large relative to their M1s. This morphology is not associated with an increase in the size of the premolar row relative to mandibular length. This combination challenges the idea that hard-object feeders have large premolars as an adaptive response to resisting the loads incurred when processing mechanically challenging foods. We therefore interpret the large P4/M1 ratios of hard-object feeders as indicating greater functional integration across the premolar-molar boundary owing to a mesial shift in preferred bite point. Finally, in a restricted subset of anthropoids, we found that, relative to mandibular length, premolar area increases with dietary elastic modulus (E) and toughness (R), indicating that relative premolar size is evolutionarily sensitive to food mechanical properties. Thus, our results show that relative premolar size is correlated with diet, highlighting the importance of this region for understanding the evolutionary history of primate dietary adaptations.}, } @article {pmid29793791, year = {2018}, author = {Beaudet, A and Carlson, KJ and Clarke, RJ and de Beer, F and Dhaene, J and Heaton, JL and Pickering, TR and Stratford, D}, title = {Cranial vault thickness variation and inner structural organization in the StW 578 hominin cranium from Jacovec Cavern, South Africa.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {204-220}, doi = {10.1016/j.jhevol.2018.04.004}, pmid = {29793791}, issn = {1095-8606}, abstract = {The Sterkfontein Caves site is one of the richest early hominin fossil localities in Africa. More specifically, the fossiliferous deposits within the lower-lying Jacovec Cavern have yielded valuable hominin remains; prominent among them is the Australopithecus partial cranium StW 578. Due to the fragmentary nature of the braincase, the specimen has not yet been formally assigned to a species. In this context, we employ microtomography to quantify cranial thickness and composition of StW 578 in order to assess its taxonomic affinity. As comparative material, we investigate 10 South African hominin cranial specimens from Sterkfontein (StW 505, Sts 5, Sts 25, Sts 71), Swartkrans (SK 46, SK 48, SK 49) and Makapansgat (MLD 1, MLD 10, MLD 37/38), attributed to either Australopithecus or Paranthropus, as well as 10 extant human and 10 extant chimpanzee crania. Thickness variation in and structural arrangement of the inner and outer cortical tables and the diploë are automatically assessed at regular intervals along one parasagittal and one coronal section. Additionally, topographic cranial vault thickness distribution is visualized using color maps. Comparisons highlight an absolutely and relatively thickened condition of the StW 578 cranial vault versus those of other South African Plio-Pleistocene hominins. Moreover, in StW 578, as well as in the Australopithecus specimens Sts 5 and Sts 71 from Sterkfontein, the diploic layer contributes substantially to cumulative vault thickness (i.e., >60%). Within the comparative sample investigated here, StW 505 and Sts 71 from Sterkfontein Member 4, both attributed to Australopithecus, most closely resemble StW 578 in terms of cranial vault thickness values, tissue proportions, and two- and three-dimensional distributions. Including additional Plio-Pleistocene Australopithecus and Paranthropus crania from South and East Africa in future studies would further help establish morphological variability in these hominin taxa.}, } @article {pmid29793551, year = {2018}, author = {Haftu, H and Hailu, T and Medhaniye, A and G/Tsadik, T}, title = {Assessment of pattern and treatment outcome of patients admitted to pediatric intensive care unit, Ayder Referral Hospital, Tigray, Ethiopia, 2015.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {339}, pmid = {29793551}, issn = {1756-0500}, mesh = {Adolescent ; Child ; Child, Preschool ; Ethiopia ; Female ; *Hospital Mortality ; Hospitalization/*statistics & numerical data ; Humans ; Infant ; Infant, Newborn ; Intensive Care Units, Pediatric/*statistics & numerical data ; Male ; Meningitis/therapy ; Outcome Assessment (Health Care)/*statistics & numerical data ; }, abstract = {OBJECTIVE: To describe admission pattern and outcome with its predictor variable on the mortality of children admitted to pediatric intensive care unit (PICU), Ayder Referral Hospital, Northern Ethiopia, from September 2012 to August 2014.

RESULT: From 680 admitted patients, 400 patients were analyzed. Average age at admission was 62.99 ± 60.94 months, with F:M ratio of 1:1.2. Overall (from infectious and non-infectious) the most commonly affected systems were respiratory (90/400 pts., 22.5%) and central nervous system (83/400 pts., 20.75%). Most were admitted due to meningitis (44/400 pts., 11%), post-operative (43/400 pts., 10.8%) and acute glomerulonephritis (41/400 pts., 10.3%). The overall mortality rate was 8.5%. Multivariable logistic regression shows, use of inotropes (p = 0.000), need for mechanical ventilator (p = 0.007) and presence of comorbid illness (p = 0.002), infectious cause (p = 0.015) and low level of Glasgow coma scale less than eight (p = 0.04) were independent predictors of mortality. From this study, common cause of PICU admission and death was meningitis. This highlights the importance of focusing on the preventable methods in the public such as vaccine, creating awareness about hygiene, and expanding ICU for early detection and for treatment acutely ill children.}, } @article {pmid29793542, year = {2018}, author = {Li, LG and Yin, X and Zhang, T}, title = {Tracking antibiotic resistance gene pollution from different sources using machine-learning classification.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {93}, pmid = {29793542}, issn = {2049-2618}, support = {172099/14E//Hong Kong General Research Fund/International ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects/*genetics ; China ; Drug Resistance, Microbial/*genetics ; Gastrointestinal Microbiome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; *Machine Learning ; Metagenomics ; Sewage/*microbiology ; Soil Microbiology ; }, abstract = {BACKGROUND: Antimicrobial resistance (AMR) has been a worldwide public health concern. Current widespread AMR pollution has posed a big challenge in accurately disentangling source-sink relationship, which has been further confounded by point and non-point sources, as well as endogenous and exogenous cross-reactivity under complicated environmental conditions. Because of insufficient capability in identifying source-sink relationship within a quantitative framework, traditional antibiotic resistance gene (ARG) signatures-based source-tracking methods would hardly be a practical solution.

RESULTS: By combining broad-spectrum ARG profiling with machine-learning classification SourceTracker, here we present a novel way to address the question in the era of high-throughput sequencing. Its potential in extensive application was firstly validated by 656 global-scale samples covering diverse environmental types (e.g., human/animal gut, wastewater, soil, ocean) and broad geographical regions (e.g., China, USA, Europe, Peru). Its potential and limitations in source prediction as well as effect of parameter adjustment were then rigorously evaluated by artificial configurations with representative source proportions. When applying SourceTracker in region-specific analysis, excellent performance was achieved by ARG profiles in two sample types with obvious different source compositions, i.e., influent and effluent of wastewater treatment plant. Two environmental metagenomic datasets of anthropogenic interference gradient further supported its potential in practical application. To complement general-profile-based source tracking in distinguishing continuous gradient pollution, a few generalist and specialist indicator ARGs across ecotypes were identified in this study.

CONCLUSION: We demonstrated for the first time that the developed source-tracking platform when coupling with proper experiment design and efficient metagenomic analysis tools will have significant implications for assessing AMR pollution. Following predicted source contribution status, risk ranking of different sources in ARG dissemination will be possible, thereby paving the way for establishing priority in mitigating ARG spread and designing effective control strategies.}, } @article {pmid29793539, year = {2018}, author = {McIntosh, CM and Chen, L and Shaiber, A and Eren, AM and Alegre, ML}, title = {Gut microbes contribute to variation in solid organ transplant outcomes in mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {96}, pmid = {29793539}, issn = {2049-2618}, support = {P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 AI115716/AI/NIAID NIH HHS/United States ; R01 AI115716//National Institute of Allergy and Infectious Diseases/International ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Feces/microbiology ; Female ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Graft Rejection/*microbiology ; Graft Survival/*physiology ; Mice ; Mice, Inbred C57BL ; *Organ Transplantation ; Skin/microbiology ; *Skin Transplantation ; Treatment Outcome ; }, abstract = {BACKGROUND: Solid organ transplant recipients show heterogeneity in the occurrence and timing of acute rejection episodes. Understanding the factors responsible for such variability in patient outcomes may lead to improved diagnostic and therapeutic approaches. Rejection kinetics of transplanted organs mainly depends on the extent of genetic disparities between donor and recipient, but a role for environmental factors is emerging. We have recently shown that major alterations of the microbiota following broad-spectrum antibiotics, or use of germ-free animals, promoted longer skin graft survival in mice. Here, we tested whether spontaneous differences in microbial colonization between genetically similar individuals can contribute to variability in graft rejection kinetics.

RESULTS: We compared rejection kinetics of minor mismatched skin grafts in C57BL/6 mice from Jackson Laboratory (Jax) and Taconic Farms (Tac), genetically similar animals colonized by different commensal microbes. Female Tac mice rejected skin grafts from vendor-matched males more quickly than Jax mice. We observed prolonged graft survival in Tac mice when they were exposed to Jax mice microbiome through co-housing or fecal microbiota transplantation (FMT) by gastric gavage. In contrast, exposure to Tac mice did not change graft rejection kinetics in Jax mice, suggesting a dominant suppressive effect of Jax microbiota. High-throughput sequencing of 16S rRNA gene amplicons from Jax and Tac mice fecal samples confirmed a convergence of microbiota composition after cohousing or fecal transfer. Our analysis of amplicon data associated members of a single bacterial genus, Alistipes, with prolonged graft survival. Consistent with this finding, members of the genus Alistipes were absent in a separate Tac cohort, in which fecal transfer from Jax mice failed to prolong graft survival.

CONCLUSIONS: These results demonstrate that differences in resident microbiome in healthy individuals may translate into distinct kinetics of graft rejection, and contribute to interpersonal variability in graft outcomes. The association between Alistipes and prolonged skin graft survival in mice suggests that members of this genus might affect host physiology, including at sites distal to the gastrointestinal tract. Overall, these findings allude to a potential therapeutic role for specific gut microbes to promote graft survival through the administration of probiotics, or FMT.}, } @article {pmid29793532, year = {2018}, author = {Bilen, M and Dufour, JC and Lagier, JC and Cadoret, F and Daoud, Z and Dubourg, G and Raoult, D}, title = {The contribution of culturomics to the repertoire of isolated human bacterial and archaeal species.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {94}, pmid = {29793532}, issn = {2049-2618}, mesh = {Actinobacteria/isolation & purification ; Archaea/*classification/genetics/*isolation & purification ; Bacteria/*classification/genetics/*isolation & purification ; Bacteroidetes/isolation & purification ; DNA, Archaeal/genetics ; DNA, Bacterial/genetics ; Firmicutes/isolation & purification ; Gastrointestinal Microbiome/*genetics ; Humans ; Metagenomics ; Proteobacteria/isolation & purification ; }, abstract = {After a decade of research and metagenomic analyses, our knowledge of the human microbiota appears to have reached a plateau despite promising results. In many studies, culture has proven to be essential in describing new prokaryotic species and filling metagenomic gaps. In 2015, only 2172 different prokaryotic species were reported to have been isolated at least once from the human body as pathogens or commensals. In this review, we update the previous repertoire by reporting the different species isolated from the human body to date, increasing it by 28% to reach a total of 2776 species associated with human beings. They have been classified into 11 different phyla, mostly the Firmicutes, Proteobacteria, Bacteroidetes, and Actinobacteria. Finally, culturomics contributed up to 66.2% towards updating this repertoire by reporting 400 species, of which 288 were novel. This demonstrates the need to continue the culturing work, which seems essential in order to decipher the hidden human microbial content.}, } @article {pmid29793531, year = {2018}, author = {Robertson, RC and Kaliannan, K and Strain, CR and Ross, RP and Stanton, C and Kang, JX}, title = {Maternal omega-3 fatty acids regulate offspring obesity through persistent modulation of gut microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {95}, pmid = {29793531}, issn = {2049-2618}, support = {K01 DK002970/DK/NIDDK NIH HHS/United States ; SFI/12/RC/2273//Science Foundation Ireland/Ireland ; HRA_POR/2011/23//Health Research Board/Ireland ; HRA_POR/2012/32//Health Research Board/Ireland ; }, mesh = {Animals ; Animals, Newborn/metabolism/microbiology ; Bacteroides/isolation & purification ; Clostridiaceae/isolation & purification ; *Diet, High-Fat ; Epsilonproteobacteria/isolation & purification ; Fatty Acid Desaturases/genetics ; Fatty Acids, Omega-3/*metabolism ; Female ; Gastrointestinal Microbiome/*physiology ; Intestines/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Obesity/*pathology ; Verrucomicrobia/isolation & purification ; Weight Gain ; }, abstract = {BACKGROUND: The early-life gut microbiota plays a critical role in host metabolism in later life. However, little is known about how the fatty acid profile of the maternal diet during gestation and lactation influences the development of the offspring gut microbiota and subsequent metabolic health outcomes.

RESULTS: Here, using a unique transgenic model, we report that maternal endogenous n-3 polyunsaturated fatty acid (PUFA) production during gestation or lactation significantly reduces weight gain and markers of metabolic disruption in male murine offspring fed a high-fat diet. However, maternal fatty acid status appeared to have no significant effect on weight gain in female offspring. The metabolic phenotypes in male offspring appeared to be mediated by comprehensive restructuring of gut microbiota composition. Reduced maternal n-3 PUFA exposure led to significantly depleted Epsilonproteobacteria, Bacteroides, and Akkermansia and higher relative abundance of Clostridia. Interestingly, offspring metabolism and microbiota composition were more profoundly influenced by the maternal fatty acid profile during lactation than in utero. Furthermore, the maternal fatty acid profile appeared to have a long-lasting effect on offspring microbiota composition and function that persisted into adulthood after life-long high-fat diet feeding.

CONCLUSIONS: Our data provide novel evidence that weight gain and metabolic dysfunction in adulthood is mediated by maternal fatty acid status through long-lasting restructuring of the gut microbiota. These results have important implications for understanding the interaction between modern Western diets, metabolic health, and the intestinal microbiome.}, } @article {pmid29793516, year = {2018}, author = {Elsner, B and Schweder, S and Mehrholz, J}, title = {Immediate effects of rest periods on balance control in patients after stroke. A randomized controlled pilot trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {338}, pmid = {29793516}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Exercise Therapy/*methods ; Female ; Humans ; Male ; Middle Aged ; *Outcome Assessment (Health Care) ; Pilot Projects ; Postural Balance/*physiology ; Rest/*physiology ; Stroke/*therapy ; Stroke Rehabilitation/*methods ; }, abstract = {OBJECTIVES: This randomized controlled trial evaluates the effects of two different rest periods between as set of balance exercises after stroke during inpatient rehabilitation.

RESULTS: Twenty patients after stroke [11 males; mean (SD) age 65.4 (11.5) years; duration of illness 5.3 (3.4) weeks; 16 (80%) left-sided strokes] were randomly allocated into two groups of either a full rest (FR) of 4 min (n = 10) or a short rest (SR) of 1 min between exercise sets (n = 10). Patients improved from baseline until immediately after exercises in one-leg standing time on the affected leg [SR: mean difference 5.1 s (SD 10.3) and FR: 2.0 s (2.4)] and tandem standing time (TST). [SR: 14.9 s (SD 24.6) and FR: 5.7 s (12.0)], but OLST and TST did not differ significantly between groups (p = 0.35 and p = 0.52, respectively). Trial registration The study was registered retrospectively in the German Register of Clinical Trials with the ID: DRKS00013979.}, } @article {pmid29793448, year = {2018}, author = {Wang, M and Hancock, TP and Chamberlain, AJ and Vander Jagt, CJ and Pryce, JE and Cocks, BG and Goddard, ME and Hayes, BJ}, title = {Putative bovine topological association domains and CTCF binding motifs can reduce the search space for causative regulatory variants of complex traits.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {395}, pmid = {29793448}, issn = {1471-2164}, mesh = {Animals ; CCCTC-Binding Factor/*metabolism ; Cattle ; *Genomics ; *Nucleotide Motifs ; Protein Binding ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: Topological association domains (TADs) are chromosomal domains characterised by frequent internal DNA-DNA interactions. The transcription factor CTCF binds to conserved DNA sequence patterns called CTCF binding motifs to either prohibit or facilitate chromosomal interactions. TADs and CTCF binding motifs control gene expression, but they are not yet well defined in the bovine genome. In this paper, we sought to improve the annotation of bovine TADs and CTCF binding motifs, and assess whether the new annotation can reduce the search space for cis-regulatory variants.

RESULTS: We used genomic synteny to map TADs and CTCF binding motifs from humans, mice, dogs and macaques to the bovine genome. We found that our mapped TADs exhibited the same hallmark properties of those sourced from experimental data, such as housekeeping genes, transfer RNA genes, CTCF binding motifs, short interspersed elements, H3K4me3 and H3K27ac. We showed that runs of genes with the same pattern of allele-specific expression (ASE) (either favouring paternal or maternal allele) were often located in the same TAD or between the same conserved CTCF binding motifs. Analyses of variance showed that when averaged across all bovine tissues tested, TADs explained 14% of ASE variation (standard deviation, SD: 0.056), while CTCF explained 27% (SD: 0.078). Furthermore, we showed that the quantitative trait loci (QTLs) associated with gene expression variation (eQTLs) or ASE variation (aseQTLs), which were identified from mRNA transcripts from 141 lactating cows' white blood and milk cells, were highly enriched at putative bovine CTCF binding motifs. The linearly-furthermost, and most-significant aseQTL and eQTL for each genic target were located within the same TAD as the gene more often than expected (Chi-Squared test P-value < 0.001).

CONCLUSIONS: Our results suggest that genomic synteny can be used to functionally annotate conserved transcriptional components, and provides a tool to reduce the search space for causative regulatory variants in the bovine genome.}, } @article {pmid29793441, year = {2018}, author = {Yang, J and Qu, Y and Huang, Y and Lei, F}, title = {Dynamic transcriptome profiling towards understanding the morphogenesis and development of diverse feather in domestic duck.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {391}, pmid = {29793441}, issn = {1471-2164}, support = {KSZD-EW-Z-005-003//the Chinese Academy of Sciences/ ; O529YX5105//the Key Laboratory of the Zoological Systematics and Evolution of the Chinese Academy of Sciences/ ; }, mesh = {Animals ; Ducks/*genetics/*growth & development ; Feathers/*growth & development/metabolism ; *Gene Expression Profiling ; Gene Ontology ; Gene Regulatory Networks ; Genomics ; Molecular Sequence Annotation ; Morphogenesis/*genetics ; }, abstract = {BACKGROUND: Feathers with complex and fine structure are hallmark avian integument appendages, which have contributed significantly to the survival and breeding for birds. Here, we aimed to explore the differentiation, morphogenesis and development of diverse feathers in the domestic duck.

RESULTS: Transcriptome profiles of skin owing feather follicle from two body parts at three physiological stages were constructed to understand the molecular network and excavate the candidate genes associated with the development of plumulaceous and flight feather structures. The venn analysis of differentially expressed genes (DEGs) between abdomen and wing skin tissues at three developmental stages showed that 38 genes owing identical differentially expression pattern. Together, our data suggest that feather morphological and structural diversity can be possibly related to the homeobox proteins. The key series-clusters, many candidate biological processes and genes were identified for the morphogenesis, growth and development of two feather types. Through comparing the results of developmental transcriptomes from plumulaceous and flight feather, we found that DEGs belonging to the family of WNT, FGF and BMP have certain differences; even the consistent DEGs of skin and feather follicle transcriptomes from abdomen and wing have the different expression patterns.

CONCLUSIONS: Overall, this study detected many functional genes and showed differences in the molecular mechanisms of diverse feather developments. The findings in WNT, FGF and BMP, which were consistent with biological experiments, showed more possible complex modulations. A correlative role of HOX genes was also suggested but future biological verification experiments are required. This work provided valuable information for subsequent research on the morphogenesis of feathers.}, } @article {pmid29793435, year = {2018}, author = {Cao, K and Yu, J and Xu, D and Ai, K and Bao, E and Zou, Z}, title = {Exposure to lower red to far-red light ratios improve tomato tolerance to salt stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {92}, pmid = {29793435}, issn = {1471-2229}, support = {2016BZ09//the study on key technologies for healthy production of efficient resources utilization in protected vegetables/ ; CX161002//research on key technologies and supporting equipment of protected vegetable production/ ; AA16380048//the achievement transformation of multilayer stereo water culture/ ; }, mesh = {Antioxidants/metabolism ; Chlorophyll/metabolism ; Fluorescence ; Free Radical Scavengers/metabolism ; Hydrogen Peroxide/metabolism ; Infrared Rays ; Lycopersicon esculentum/*physiology/radiation effects ; Malondialdehyde/metabolism ; Peroxidases/metabolism ; Photosynthesis ; Phytochrome/metabolism ; Proline/metabolism ; Reactive Oxygen Species/metabolism ; Salinity ; Salt Stress ; Salt Tolerance ; }, abstract = {BACKGROUND: Red (R) and far-red (FR) light distinctly influence phytochrome-mediated initial tomato growth and development, and more recent evidence indicates that these spectra also modulate responses to a multitude of abiotic and biotic stresses. This research investigated whether different R: FR values affect tomato growth response and salinity tolerance. Tomato seedlings were exposed to different R: FR conditions (7.4, 1.2 and 0.8) under salinity stress (100 mM NaCl), and evaluated for their growth, biochemical changes, active reactive oxygen species (ROS) and ROS scavenging enzymes, pigments, rate of photosynthesis, and chlorophyll fluorescence.

RESULTS: The results showed that under conditions of salinity, tomato seedlings subjected to a lower R: FR value (0.8) significantly increased both their growth, proline content, chlorophyll content and net photosynthesis rate (Pn), while they decreased malondialdehyde (MDA) compared to the higher R: FR value (7.4). Under conditions of salinity, the lower R: FR value caused a decrease in both the superoxide anion (O2•-) and in hydrogen peroxide (H2O2) generation, an increase in the activities of superoxidase dismutase (SOD, EC 1.15.1.1), peroxidase (POD, EC 1.11.1.7) and catalase (CAT, EC 1.11.1.7). Tomato seedlings grown under the lower R: FR value and conditions of salinity showed a higher actual quantum yield of photosynthesis (ΦPSII), electron transport rate (ETR), and photochemical quenching (qP) than those exposed to a higher R: FR, indicating overall healthier growth. However, the salinity tolerance induced at the lower R: FR condition disappeared in the tomato phyB1 mutant.

CONLUSION: These results suggest that growing tomato with a lower R: FR value could improve seedlings' salinity tolerance, and phytochrome B1 play an very important role in this process. Therefore, different qualities of light can be used to efficiently develop abiotic stress tolerance in tomato cultivation.}, } @article {pmid29793434, year = {2018}, author = {Guo, W and Liu, Y and Ng, WL and Liao, PC and Huang, BH and Li, W and Li, C and Shi, X and Huang, Y}, title = {Comparative transcriptome analysis of the invasive weed Mikania micrantha with its native congeners provides insights into genetic basis underlying successful invasion.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {392}, pmid = {29793434}, issn = {1471-2164}, support = {41776166//National Natural Science Foundation of China/ ; 31700178//National Natural Science Foundation of China/ ; 2015A030313136//Natural Science Foundation of Guangdong Province/ ; 2017A030313159//Natural Science Foundation of Guangdong Province/ ; 2017A030303014//Special Fund for Science and Technology Development of Guangdong Province/ ; 201707020035//the Science and Technology Program of Guangzhou/ ; 32-2017-A30//the Science Foundation of the State Key Laboratory of Biocontrol/ ; }, mesh = {Evolution, Molecular ; *Gene Expression Profiling ; *Introduced Species ; Mikania/*genetics/growth & development ; Molecular Sequence Annotation ; Phylogeny ; Plant Weeds/*genetics/growth & development ; Selection, Genetic ; }, abstract = {BACKGROUND: Mikania micrantha H.B.K. (Asteraceae) is one of the world's most invasive weeds which has been rapidly expanding in tropical Asia, including China, while its close relative M. cordata, the only Mikania species native to China, shows no harm to the local ecosystems. These two species are very similar in morphology but differ remarkably in several ecological and physiological traits, representing an ideal system for comparative analysis to investigate the genetic basis underlying invasion success. In this study, we performed RNA-sequencing on the invader M. micrantha and its native congener M. cordata in China, to unravel the genetic basis underlying the strong invasiveness of M. micrantha. For a more robust comparison, another non-invasive congener M. cordifolia was also sequenced and compared.

RESULTS: A total of 52,179, 55,835, and 52,983 unigenes were obtained for M. micrantha, M. cordata, and M. cordifolia, respectively. Phylogenetic analyses and divergence time dating revealed a relatively recent split between M. micrantha and M. cordata, i.e., approximately 4.81 million years ago (MYA), after their divergence with M. cordifolia (8.70 MYA). Gene ontology classifications, pathway assignments and differential expression analysis revealed higher representation or significant up-regulation of genes associated with photosynthesis, energy metabolism, protein modification and stress response in M. micrantha than in M. cordata or M. cordifolia. Analysis of accelerated evolution and positive selection also suggested the importance of these related genes and processes to the adaptability and invasiveness of M. micrantha. Particularly, most (77 out of 112, i.e. 68.75%) positively selected genes found in M. micrantha could be classified into four groups, i.e., energy acquisition and utilization (10 genes), growth and reproduction (13 genes), protection and repair (34 genes), and signal transduction and expression regulation (20 genes), which may have contributed to the high adaptability of M. micrantha to various new environments and the capability to occupy a wider niche, reflected in its high invasiveness.

CONCLUSIONS: We characterized the transcriptomes of the invasive species M. micrantha and its non-invasive congeners, M. cordata and M. cordifolia. A comparison of their transcriptomes provided insights into the genetic basis of the high invasiveness of M. micrantha.}, } @article {pmid29793430, year = {2018}, author = {Belahbib, H and Renard, E and Santini, S and Jourda, C and Claverie, JM and Borchiellini, C and Le Bivic, A}, title = {New genomic data and analyses challenge the traditional vision of animal epithelium evolution.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {393}, pmid = {29793430}, issn = {1471-2164}, mesh = {Adherens Junctions/metabolism ; Amino Acid Sequence ; Animals ; Cadherins/chemistry/genetics/metabolism ; Ctenophora/genetics/metabolism ; Epithelium/*metabolism ; *Evolution, Molecular ; *Genomics ; Porifera/genetics/metabolism ; Protein Domains ; }, abstract = {BACKGROUND: The emergence of epithelia was the foundation of metazoan expansion. Epithelial tissues are a hallmark of metazoans deeply rooted in the evolution of their complex developmental morphogenesis processes. However, studies on the epithelial features of non-bilaterians are still sparse and it remains unclear whether the last common metazoan ancestor possessed a fully functional epithelial toolkit or if it was acquired later during metazoan evolution.

RESULTS: To investigate the early evolution of animal epithelia, we sequenced the genome and transcriptomes of two new sponge species to characterize epithelial markers such as the E-cadherin complex and the polarity complexes for all classes (Calcarea, Demospongiae, Hexactinellida, Homoscleromorpha) of sponges (phylum Porifera) and compare them with their homologues in Placozoa and in Ctenophora. We found that Placozoa and most sponges possess orthologues of all essential genes encoding proteins characteristic of bilaterian epithelial cells, as well as their conserved interaction domains. In stark contrast, we found that ctenophores lack several major polarity complex components such as the Crumbs complex and Scribble. Furthermore, the E-cadherin ctenophore orthologue exhibits a divergent cytoplasmic domain making it unlikely to interact with its canonical cytoplasmic partners.

CONCLUSIONS: These unexpected findings challenge the current evolutionary paradigm on the emergence of epithelia. Altogether, our results raise doubt on the homology of protein complexes and structures involved in cell polarity and adhesive-type junctions between Ctenophora and Bilateria epithelia.}, } @article {pmid29793428, year = {2018}, author = {Lan, Y and Sun, J and Xu, T and Chen, C and Tian, R and Qiu, JW and Qian, PY}, title = {De novo transcriptome assembly and positive selection analysis of an individual deep-sea fish.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {394}, pmid = {29793428}, issn = {1471-2164}, support = {XDB06010102//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, mesh = {Adaptation, Physiological ; Animals ; Evolution, Molecular ; Fishes/*genetics ; *Gene Expression Profiling ; Phylogeny ; *Selection, Genetic ; }, abstract = {BACKGROUND: High hydrostatic pressure and low temperatures make the deep sea a harsh environment for life forms. Actin organization and microtubules assembly, which are essential for intracellular transport and cell motility, can be disrupted by high hydrostatic pressure. High hydrostatic pressure can also damage DNA. Nucleic acids exposed to low temperatures can form secondary structures that hinder genetic information processing. To study how deep-sea creatures adapt to such a hostile environment, one of the most straightforward ways is to sequence and compare their genes with those of their shallow-water relatives.

RESULTS: We captured an individual of the fish species Aldrovandia affinis, which is a typical deep-sea inhabitant, from the Okinawa Trough at a depth of 1550 m using a remotely operated vehicle (ROV). We sequenced its transcriptome and analyzed its molecular adaptation. We obtained 27,633 protein coding sequences using an Illumina platform and compared them with those of several shallow-water fish species. Analysis of 4918 single-copy orthologs identified 138 positively selected genes in A. affinis, including genes involved in microtubule regulation. Particularly, functional domains related to cold shock as well as DNA repair are exposed to positive selection pressure in both deep-sea fish and hadal amphipod.

CONCLUSIONS: Overall, we have identified a set of positively selected genes related to cytoskeleton structures, DNA repair and genetic information processing, which shed light on molecular adaptation to the deep sea. These results suggest that amino acid substitutions of these positively selected genes may contribute crucially to the adaptation of deep-sea animals. Additionally, we provide a high-quality transcriptome of a deep-sea fish for future deep-sea studies.}, } @article {pmid29793423, year = {2018}, author = {Li, D and Yang, MQ}, title = {Correction to: Identification and characterization of conserved lncRNAs in human and rat brain.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {181}, pmid = {29793423}, issn = {1471-2105}, abstract = {After publication of the original article [1], it was noticed that the Acknowledgement statement was incorrect. The original statement reads.}, } @article {pmid29793422, year = {2018}, author = {Xiang, KL and Erst, AS and Xiang, XG and Jabbour, F and Wang, W}, title = {Biogeography of Coptis Salisb. (Ranunculales, Ranunculaceae, Coptidoideae), an Eastern Asian and North American genus.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {74}, pmid = {29793422}, issn = {1471-2148}, support = {XDPB0203//the Strategic Priority Research Program of the Chinese Academy of Sciences/International ; 2014CB954100//the National Basic Research Program of China/International ; 31270269, 31770231 and 31470315//the National Natural Science Foundation of China/International ; }, mesh = {Bayes Theorem ; Coptis/*classification ; Far East ; Models, Biological ; North America ; Phylogeny ; *Phylogeography ; Sequence Analysis, DNA ; Species Specificity ; Time Factors ; }, abstract = {BACKGROUND: Numerous studies have favored dispersal (colonization) over vicariance (past fragmentation) events to explain eastern Asian-North American distribution patterns. In plants, however the disjunction between eastern Asia and western North America has been rarely examined using the integration of phylogenetic, molecular dating, and biogeographical methods. Meanwhile, the biogeographic patterns within eastern Asia remain poorly understood. The goldthread genus Coptis Salisb. includes 15 species disjunctly distributed in North America, Japan, mainland China, and Taiwan. We present a dated phylogeny for Coptis under the optimal clock model and infer its historical biogeography by comparing different biogeographic models.

RESULTS: The split of Coptis and Xanthorhiza Marshall occurred in the middle Miocene (ca. 15.47 Ma). Coptis started their diversification in the early late Miocene (ca. 9.55 Ma). A late Miocene vicariance event resulted in the eastern Asian and western North American disjunction in the genus. Within eastern Asia, dispersals from mainland Asia to Japan and from Japan to Taiwan occurred at ca. 4.85 Ma and at ca. 1.34 Ma, respectively.

CONCLUSIONS: Our analyses provide evidence that both vicariance and dispersal events have played important roles in shaping the current distribution and endemism of Coptis, likely resulting from eustatic sea-level changes, mountain formation processes and an increasing drier and cooler climate from the middle Miocene onwards.}, } @article {pmid29793421, year = {2018}, author = {Leduc, A and Zatylny-Gaudin, C and Robert, M and Corre, E and Corguille, GL and Castel, H and Lefevre-Scelles, A and Fournier, V and Gisbert, E and Andree, KB and Henry, J}, title = {Dietary aquaculture by-product hydrolysates: impact on the transcriptomic response of the intestinal mucosa of European seabass (Dicentrarchus labrax) fed low fish meal diets.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {396}, pmid = {29793421}, issn = {1471-2164}, support = {2014/1274//Association Nationale de la Recherche et de la Technologie/ ; AGL2014-51839-C6-5-R//Ministerio de Economía y Competitividad/ ; AGL2014-51839-C6-5-R//Ministerio de Economía y Competitividad/ ; }, mesh = {Animal Feed/*analysis ; Animals ; *Aquaculture ; Bass/*genetics ; Dietary Proteins/*chemistry ; Hydrolysis ; Intestinal Mucosa/*drug effects/*metabolism ; Metabolic Networks and Pathways/drug effects ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: Aquaculture production is expected to double by 2030, and demands for aquafeeds and raw materials are expected to increase accordingly. Sustainable growth of aquaculture will require the development of highly nutritive and functional raw materials to efficiently replace fish meal. Enzymatic hydrolysis of marine and aquaculture raw materials could bring new functionalities to finished products. The aim of this study was to determine the zootechnical and transcriptomic performances of protein hydrolysates of different origins (tilapia, shrimp, and a combination of the two) in European seabass (Dicentrarchux labrax) fed a low fish meal diet (5%), for 65 days.

RESULTS: Results were compared to a positive control fed with 20% of fish meal. Growth performances, anterior intestine histological organization and transcriptomic responses were monitored and analyzed. Dietary inclusion of protein hydrolysates in the low fish meal diet restored similar growth performances to those of the positive control. Inclusion of dietary shrimp hydrolysate resulted in larger villi and more goblet cells, even better than the positive control. Transcriptomic analysis of the anterior intestine showed that dietary hydrolysate inclusion restored a pattern of intestinal gene expression very close to the pattern of the positive control. However, as compared to the low fish meal diet and depending on their origin, the different hydrolysates did not modulate metabolic pathways in the same way. Dietary shrimp hydrolysate inclusion modulated more metabolic pathways related to immunity, while nutritional metabolism was more impacted by dietary tilapia hydrolysate. Interestingly, the combination of the two hydrolysates enhanced the benefits of hydrolysate inclusion in diets: more genes and metabolic pathways were regulated by the combined hydrolysates than by each hydrolysate tested independently.

CONCLUSIONS: Protein hydrolysates manufactured from aquaculture by-products are promising candidates to help replace fish meal in aquaculture feeds without disrupting animal metabolism and performances.}, } @article {pmid29792856, year = {2018}, author = {Watanabe, T and Nakamura, R and Takase, Y and Susaki, EA and Ueda, HR and Tadokoro, R and Takahashi, Y}, title = {Comparison of the 3-D patterns of the parasympathetic nervous system in the lung at late developmental stages between mouse and chicken.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.05.014}, pmid = {29792856}, issn = {1095-564X}, abstract = {Although the basic schema of the body plan is similar among different species of amniotes (mammals, birds, and reptiles), the lung is an exception. Here, anatomy and physiology are considerably different, particularly between mammals and birds. In mammals, inhaled and exhaled airs mix in the airways, whereas in birds the inspired air flows unidirectionally without mixing with the expired air. This bird-specific respiration system is enabled by the complex tubular structures called parabronchi where gas exchange takes place, and also by the bellow-like air sacs appended to the main part of the lung. That the lung is predominantly governed by the parasympathetic nervous system has been shown mostly by physiological studies in mammals. However, how the parasympathetic nervous system in the lung is established during late development has largely been unexplored both in mammals and birds. In this study, by combining immunocytochemistry, the tissue-clearing CUBIC method, and ink-injection to airways, we have visualized the 3-D distribution patterns of parasympathetic nerves and ganglia in the lung at late developmental stages of mice and chickens. These patterns were further compared between these species, and three prominent similarities emerged: (1) parasympathetic postganglionic fibers and ganglia are widely distributed in the lung covering the proximal and distal portions, (2) the gas exchange units, alveoli in mice and parabronchi in chickens, are devoid of parasympathetic nerves, (3) parasympathetic nerves are in close association with smooth muscle cells, particularly at the base of the gas exchange units. These observations suggest that despite gross differences in anatomy, the basic mechanisms underlying parasympathetic control of smooth muscles and gas exchange might be conserved between mammals and birds.}, } @article {pmid29792855, year = {2018}, author = {Xiang, L and Yu, H and Zhang, X and Wang, B and Yuan, Y and Zhang, Q and Ye, R and Gong, P and Wu, Y}, title = {The versatile hippo pathway in oral-maxillofacial development and bone remodeling.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {53-63}, doi = {10.1016/j.ydbio.2018.05.017}, pmid = {29792855}, issn = {1095-564X}, mesh = {Animals ; Bone Remodeling/*physiology ; Cell Proliferation ; Drosophila Proteins/metabolism/physiology ; Humans ; Intracellular Signaling Peptides and Proteins/metabolism/physiology ; Maxillofacial Development/*physiology ; Mice ; Protein-Serine-Threonine Kinases/metabolism/*physiology ; Signal Transduction/physiology ; Stem Cells/metabolism ; Transcription Factors/metabolism ; }, abstract = {The Hippo signaling pathway is implicated in key aspects of cell proliferation, control of organ size, stem cell functions and tumor suppression. Its functions are primarily mediated either through direct effects on transcription factors to influence target gene expression or through crosstalk with other signaling pathways that regulate multiple physiological activities. Studies are revealing Hippo pathway involvement in diverse functions including renewal of intestinal epithelium, promotion of myocardial cell proliferation, cancer suppression, etc. In this review we discuss Hippo pathway signaling in oral-maxillofacial development and bone remodeling under normal and pathological conditions and highlight promising future research directions.}, } @article {pmid29792854, year = {2018}, author = {Cheng, FY and Fleming, JT and Chiang, C}, title = {Bergmann glial Sonic hedgehog signaling activity is required for proper cerebellar cortical expansion and architecture.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {152-166}, pmid = {29792854}, issn = {1095-564X}, support = {F31 NS074638/NS/NINDS NIH HHS/United States ; R01 NS097898/NS/NINDS NIH HHS/United States ; T32 GM007347/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/metabolism ; Cell Differentiation ; Cell Division ; Cell Proliferation/physiology ; Cells, Cultured ; Cerebellar Cortex/*embryology/physiology ; Cerebellar Neoplasms/metabolism ; Cerebellum/abnormalities/embryology ; Developmental Disabilities/genetics ; Hedgehog Proteins/metabolism/*physiology ; Mice ; Nervous System Malformations/embryology/genetics ; Neural Stem Cells/cytology/metabolism ; Neuroglia/*physiology ; Neurons/metabolism ; Purkinje Cells/metabolism ; Signal Transduction ; Wnt Signaling Pathway/genetics ; }, abstract = {Neuronal-glial relationships play a critical role in the maintenance of central nervous system architecture and neuronal specification. A deeper understanding of these relationships can elucidate cellular cross-talk capable of sustaining proper development of neural tissues. In the cerebellum, cerebellar granule neuron precursors (CGNPs) proliferate in response to Purkinje neuron-derived Sonic hedgehog (Shh) before ultimately exiting the cell cycle and migrating radially along Bergmann glial fibers. However, the function of Bergmann glia in CGNP proliferation remains not well defined. Interestingly, the Hh pathway is also activated in Bergmann glia, but the role of Shh signaling in these cells is unknown. In this study, we show that specific ablation of Shh signaling using the tamoxifen-inducible TNCYFP-CreER line to eliminate Shh pathway activator Smoothened in Bergmann glia is sufficient to cause severe cerebellar hypoplasia and a significant reduction in CGNP proliferation. TNCYFP-CreER; SmoF/- (SmoCKO) mice demonstrate an obvious reduction in cerebellar size within two days of ablation of Shh signaling. Mutant cerebella have severely reduced proliferation and increased differentiation of CGNPs due to a significant decrease in Shh activity and concomitant activation of Wnt signaling in SmoCKO CGNPs, suggesting that this pathway is involved in cross-talk with the Shh pathway in regulating CGNP proliferation. In addition, Purkinje cells are ectopically located, their dendrites stunted, and the Bergmann glial network disorganized. Collectively, these data demonstrate a previously unappreciated role for Bergmann glial Shh signaling activity in the proliferation of CGNPs and proper maintenance of cerebellar architecture.}, } @article {pmid29792590, year = {2018}, author = {Ma, H and Ren, H and Huang, L and Luo, Y}, title = {Altererythrobacter flavus sp. nov., isolated from mangrove sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2265-2270}, doi = {10.1099/ijsem.0.002822}, pmid = {29792590}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; *Estuaries ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhizophoraceae ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-negative, aerobic, non-motile, rod-shaped bacterium, designated MS1-4T, was isolated from mangrove sediment of the Jiulong River Estuary, Fujian Province, China. The isolate formed yellow colonies on ZB 2216E agar. Optimal growth was observed at pH 6.0, at 34 °C and in the presence of 4 % (w/v) NaCl. Strain MS1-4T shared highest 16S rRNA gene sequence similarity of 97.7 % with Altererythrobacter mangrovi C9-11T, followed by Altererythrobacter ishigakiensis JPCCMB0017T (97.2 %). Phylogenetic analysis indicated that strain MS1-4T formed a clade with A. mangrovi C9-11T within the genus Altererythrobacter. The main cellular fatty acid was summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and the sole respiratory quinone was ubiquinone Q-10. The main polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and glycolipids. The G+C content of the DNA was 60.4 mol%. Based on data from this polyphasic characterization, strain MS1-4T should be classified as representing a novel species in the genus Altererythrobacter, for which the name Altererythrobacter flavus sp. nov. is proposed. The type strain is MS1-4T (=MCCC 1K02683T=NBRC 112977T).}, } @article {pmid29792589, year = {2018}, author = {Ciufo, S and Kannan, S and Sharma, S and Badretdin, A and Clark, K and Turner, S and Brover, S and Schoch, CL and Kimchi, A and DiCuccio, M}, title = {Using average nucleotide identity to improve taxonomic assignments in prokaryotic genomes at the NCBI.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2386-2392}, doi = {10.1099/ijsem.0.002809}, pmid = {29792589}, issn = {1466-5034}, mesh = {Base Composition ; *Databases, Nucleic Acid ; *Genome, Archaeal ; *Genome, Bacterial ; Nucleotides/*genetics ; *Phylogeny ; Prokaryotic Cells ; Sequence Analysis, DNA ; }, abstract = {Average nucleotide identity analysis is a useful tool to verify taxonomic identities in prokaryotic genomes, for both complete and draft assemblies. Using optimum threshold ranges appropriate for different prokaryotic taxa, we have reviewed all prokaryotic genome assemblies in GenBank with regard to their taxonomic identity. We present the methods used to make such comparisons, the current status of GenBank verifications, and recent developments in confirming species assignments in new genome submissions.}, } @article {pmid29792588, year = {2018}, author = {Nitiyon, S and Khunnamwong, P and Lertwattanasakul, N and Limtong, S}, title = {Candida kantuleensis sp. nov., a d-xylose-fermenting yeast species isolated from peat in a tropical peat swamp forest.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2313-2318}, doi = {10.1099/ijsem.0.002835}, pmid = {29792588}, issn = {1466-5034}, mesh = {Candida/*classification/genetics/isolation & purification ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Fermentation ; Forests ; Mycological Typing Techniques ; *Phylogeny ; Sequence Analysis, DNA ; Soil Microbiology ; Thailand ; *Wetlands ; Xylose/*metabolism ; }, abstract = {Three strains (DMKU-XE11T, DMKU-XE15 and DMKU-XE20) representing a single novel anamorphic and d-xylose-fermenting yeast species were obtained from three peat samples collected from Khan Thulee peat swamp forest in Surat Thani province, Thailand. The strains differed from each other by one to two nucleotide substitutions in the sequences of the D1/D2 region of the large subunit (LSU) rRNA gene and zero to one nucleotide substitution in the internal transcribed spacer (ITS) region. Phylogenetic analysis based on the combined sequences of the ITS and the D1/D2 regions showed that the three strains represented a single Candida species that was distinct from the other related species in the Lodderomyces/Candida albicans clade. The three strains form a subclade with the other Candida species including Candida sanyaensis, Candida tropicalis and Candida sojae. C. sanyaensis was the most closely related species, with 2.1-2.4 % nucleotide substitutions in the D1/D2 region of the LSU rRNA gene, and 3.8-4.0 % nucleotide substitutions in the ITS region. The three strains (DMKU-XE11T, DMKU-XE15 and DMKU-XE20) were assigned as a single novel species, which was named Candida kantuleensis sp. nov. The type strain is DMKU-XE11T (=CBS 15219T=TBRC 7764T). The MycoBank number for C. kantuleensis sp. nov. is MB 824179.}, } @article {pmid29792222, year = {2018}, author = {Kerger, BD}, title = {Longevity and pleural mesothelioma: age-period-cohort analysis of incidence data from the Surveillance, Epidemiology, and End Results (SEER) Program, 1973-2013.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {337}, pmid = {29792222}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Aging ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Infant ; Lung Neoplasms/*epidemiology ; Male ; Mesothelioma/*epidemiology ; Middle Aged ; Pleural Neoplasms/*epidemiology ; Registries/*statistics & numerical data ; United States/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: This study investigates the hypothesis that an increasing fraction of incident pleural mesothelioma (PM) in the US population may be related to longevity, i.e., to expansion of the population over age 75 years with an age-related elevation in risk. An age-period-cohort analysis of the SEER 9 cancer registries (1973-2013) was conducted using 5-year intervals of age, calendar period, and birth cohort after stratification into four gender-age groups (male and female; 0-74 and 75+ years).

RESULTS: Gender-specific time trends in age-adjusted PM incidence by age groups were observed. After adjusting for cohort effects, males in the 0-74-year age group experienced rapidly declining PM incidence rates following the observed peak in 1978-1982, whereas continuously increasing incidence rates were observed among older males. A significant cohort effect was also observed among males in both age groups, with peak incidence rates in the 1926-1930/1928-1932 birth cohorts and thereafter. The distinct period and cohort effects among males age 0-74 years may be driven by declining age-adjusted PM incidence rates corresponding to the decline in occupational asbestos exposures post-World War II, whereas the increasing time trend seen in both genders at age 75+ may reflect an increasing proportion due to longevity-related factors.}, } @article {pmid29792182, year = {2018}, author = {Zou, LS and Erdos, MR and Taylor, DL and Chines, PS and Varshney, A and , and Parker, SCJ and Collins, FS and Didion, JP}, title = {BoostMe accurately predicts DNA methylation values in whole-genome bisulfite sequencing of multiple human tissues.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {390}, pmid = {29792182}, issn = {1471-2164}, support = {R00DK099240//National Institute of Diabetes and Digestive and Kidney Diseases/ ; 1-14-INI-07//American Diabetes Association/ ; }, mesh = {Algorithms ; Computational Biology/*methods ; DNA Methylation/*drug effects ; High-Throughput Nucleotide Sequencing ; Humans ; Sulfites/*pharmacology ; *Whole Genome Sequencing ; }, abstract = {BACKGROUND: Bisulfite sequencing is widely employed to study the role of DNA methylation in disease; however, the data suffer from biases due to coverage depth variability. Imputation of methylation values at low-coverage sites may mitigate these biases while also identifying important genomic features associated with predictive power.

RESULTS: Here we describe BoostMe, a method for imputing low-quality DNA methylation estimates within whole-genome bisulfite sequencing (WGBS) data. BoostMe uses a gradient boosting algorithm, XGBoost, and leverages information from multiple samples for prediction. We find that BoostMe outperforms existing algorithms in speed and accuracy when applied to WGBS of human tissues. Furthermore, we show that imputation improves concordance between WGBS and the MethylationEPIC array at low WGBS depth, suggesting improved WGBS accuracy after imputation.

CONCLUSIONS: Our findings support the use of BoostMe as a preprocessing step for WGBS analysis.}, } @article {pmid29792177, year = {2018}, author = {Xu, L and Wu, YH and Zhou, P and Cheng, H and Liu, Q and Xu, XW}, title = {Investigation of the thermophilic mechanism in the genus Porphyrobacter by comparative genomic analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {385}, pmid = {29792177}, issn = {1471-2164}, support = {31770004//the National Natural Science Foundation of China/ ; 41406174//the National Natural Science Foundation of China/ ; JG1527//the Scientific Research Fund of Second Institute of Oceanography, State Oceanic Administration/ ; LR17D060001//the Natural Science Foundation of Zhejiang Province/ ; }, mesh = {Alphaproteobacteria/*genetics/*physiology ; Amino Acid Substitution ; Genome, Bacterial/genetics ; *Genomics ; Phylogeny ; *Temperature ; }, abstract = {BACKGROUND: Type strains of the genus Porphyrobacter belonging to the family Erythrobacteraceae and the class Alphaproteobacteria have been isolated from various environments, such as swimming pools, lake water and hot springs. P. cryptus DSM 12079T and P. tepidarius DSM 10594T out of all Erythrobacteraceae type strains, are two type strains that have been isolated from geothermal environments. Next-generation sequencing (NGS) technology offers a convenient approach for detecting situational types based on protein sequence differences between thermophiles and mesophiles; amino acid substitutions can lead to protein structural changes, improving the thermal stabilities of proteins. Comparative genomic studies have revealed that different thermal types exist in different taxa, and few studies have been focused on the class Alphaproteobacteria, especially the family Erythrobacteraceae. In this study, eight genomes of Porphyrobacter strains were compared to elucidate how Porphyrobacter thermophiles developed mechanisms to adapt to thermal environments.

RESULTS: P. cryptus DSM 12079T grew optimally at 50 °C, which was higher than the optimal growth temperature of other Porphyrobacter type strains. Phylogenomic analysis of the genus Porphyrobacter revealed that P. cryptus DSM 12079T formed a distinct and independent clade. Comparative genomic studies uncovered that 1405 single-copy genes were shared by Porphyrobacter type strains. Alignments of single-copy proteins showed that various types of amino acid substitutions existed between P. cryptus DSM 12079T and the other Porphyrobacter strains. The primary substitution types were changes from glycine/serine to alanine.

CONCLUSIONS: P. cryptus DSM 12079T was the sole thermophile within the genus Porphyrobacter. Phylogenomic analysis and amino acid frequencies indicated that amino acid substitutions might play an important role in the thermophily of P. cryptus DSM 12079T. Bioinformatic analysis revealed that major amino acid substitutional types, such as changes from glycine/serine to alanine, increase the frequency of α-helices in proteins, promoting protein thermostability in P. cryptus DSM 12079T. Hence, comparative genomic analysis broadens our understanding of thermophilic mechanisms in the genus Porphyrobacter and may provide a useful insight in the design of thermophilic enzymes for agricultural, industrial and medical applications.}, } @article {pmid29792173, year = {2018}, author = {Geng, J and Huang, SC and Chen, YY and Chiu, CH and Hu, S and Chen, YM}, title = {Impact of growth pH and glucose concentrations on the CodY regulatory network in Streptococcus salivarius.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {386}, pmid = {29792173}, issn = {1471-2164}, support = {CMRPD1G0151//Chang Gung Memorial Hospital, Linkou/ ; MOST 105-2320-B-182-015-MY3//Ministry of Science and Technology (ROC)/ ; }, mesh = {Bacterial Proteins/*metabolism ; Dose-Response Relationship, Drug ; Glucose/*pharmacology ; Glycolysis/drug effects ; Hydrogen-Ion Concentration ; Oxidative Stress/drug effects ; Streptococcus salivarius/drug effects/*growth & development/*metabolism ; Transcription Factors/*metabolism ; }, abstract = {BACKGROUND: Streptococcus salivarius is an abundant isolate of the human oral microbiota. Since both pH and glucose availability fluctuate frequently in the oral cavity, the goal of this study was to investigate regulation by CodY, a conserved pleiotropic regulator of Gram positive bacteria, in response to these two signals. The chemostat culture system was employed to precisely control the growth parameters, and the transcriptomes of wild-type S. salivarius 57.I and its CodY-null derivative (ΔcodY) grown at pH 7 and 5.5, with limited and excessive glucose supply were determined.

RESULTS: The transcriptomic analysis revealed that CodY was most active at pH 7 under conditions of glucose limitation. Based on whether a CodY binding consensus could be located in the 5' flanking region of the identified target, the transcriptomic analysis also found that CodY shaped the transcriptome via both direct and indirect regulation. Inactivation of codY reduced the glycolytic capacity and the viability of S. salivarius at pH 5.5 or in the presence of H2O2. Studies using the Galleria mellonella larva model showed that CodY was essential for the toxicity generated from S. salivarius infection, suggesting that CodY regulation was critical for immune evasion and systemic infections. Furthermore, the CodY-null mutant strain exhibited a clumping phenotype and reduced attachment in biofilm assays, suggesting that CodY also modulates cell wall metabolism. Finally, the expression of genes belonging to the CovR regulon was affected by codY inactivation, but CodY and CovR regulated these genes in opposite directions.

CONCLUSIONS: Metabolic adaptation in response to nutrient availability and growth pH is tightly linked to stress responses and virulence expression in S. salivarius. The regulation of metabolism by CodY allows for the maximal utilization of available nutrients and ATP production. The counteractive regulation of the CovR regulon could fine tune the transcriptomes in response to environmental changes.}, } @article {pmid29792171, year = {2018}, author = {Na, W and Wu, YY and Gong, PF and Wu, CY and Cheng, BH and Wang, YX and Wang, N and Du, ZQ and Li, H}, title = {Embryonic transcriptome and proteome analyses on hepatic lipid metabolism in chickens divergently selected for abdominal fat content.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {384}, pmid = {29792171}, issn = {1471-2164}, support = {No. 2013AA102501//the National 863 project of China/ ; CARS-41//the China Agriculture Research System/ ; }, mesh = {Abdominal Fat/*metabolism ; Animals ; *Breeding ; Chick Embryo ; Chickens ; *Gene Expression Profiling ; Lipid Metabolism/*genetics ; Liver/*embryology/*metabolism ; *Proteomics ; }, abstract = {BACKGROUND: In avian species, liver is the main site of de novo lipogenesis, and hepatic lipid metabolism relates closely to adipose fat deposition. Using our fat and lean chicken lines of striking differences in abdominal fat content, post-hatch lipid metabolism in both liver and adipose tissues has been studied extensively. However, whether molecular discrepancy for hepatic lipid metabolism exists in chicken embryos remains obscure.

RESULTS: We performed transcriptome and proteome profiling on chicken livers at five embryonic stages (E7, E12, E14, E17 and E21) between the fat and lean chicken lines. At each stage, 521, 141, 882, 979 and 169 differentially expressed genes were found by the digital gene expression, respectively, which were significantly enriched in the metabolic, PPAR signaling and fatty acid metabolism pathways. Quantitative proteomics analysis found 20 differentially expressed proteins related to lipid metabolism, PPAR signaling, fat digestion and absorption, and oxidative phosphorylation pathways. Combined analysis showed that genes and proteins related to lipid transport (intestinal fatty acid-binding protein, nucleoside diphosphate kinase, and apolipoprotein A-I), lipid clearance (heat shock protein beta-1) and energy metabolism (NADH dehydrogenase [ubiquinone] 1 beta subcomplex subunit 10 and succinate dehydrogenase flavoprotein subunit) were significantly differentially expressed between the two lines.

CONCLUSIONS: For hepatic lipid metabolism at embryonic stages, molecular differences related to lipid transport, lipid clearance and energy metabolism exist between the fat and lean chicken lines, which might contribute to the striking differences of abdominal fat deposition at post-hatch stages.}, } @article {pmid29792165, year = {2018}, author = {Taneja, M and Upadhyay, SK}, title = {Molecular characterization and differential expression suggested diverse functions of P-type II Ca2+ATPases in Triticum aestivum L.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {389}, pmid = {29792165}, issn = {1471-2164}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Chromosomes, Plant/genetics ; Droughts ; Gene Duplication ; *Gene Expression Regulation, Plant/drug effects ; Genome, Plant/genetics ; Heat-Shock Response/genetics ; Intracellular Space/drug effects/metabolism ; P-type ATPases/chemistry/*genetics/metabolism ; Phylogeny ; Protein Domains ; Protein Transport/drug effects ; Salts/pharmacology ; Triticum/drug effects/*enzymology/*genetics/microbiology ; }, abstract = {BACKGROUND: Plant P-type II Ca2+ATPases are formed by two distinct groups of proteins (ACAs and ECAs) that perform pumping of Ca2+ outside the cytoplasm during homeostasis, and play vital functions during development and stress management. In the present study, we have performed identification and characterisation of P-type II Ca 2+ ATPase gene family in an important crop plant Triticum aestivum.

RESULTS: Herein, a total of 33 TaACA and 9 TaECA proteins were identified from the various chromosomes and sub-genomes of Triticum aestivum. Phylogenetic analysis revealed clustering of the homoeologous TaACA and TaECA proteins into 11 and 3 distinct groups that exhibited high sequence homology and comparable structural organization as well. Both TaACA and TaECA group proteins consisted of eight to ten transmembrane regions, and their respective domains and motifs. Prediction of sub-cellular localization was found variable for most of the proteins; moreover, it was consistent with the evolutionarily related proteins from rice and Arabidopsis in certain cases. The occurrence of assorted sets of cis-regulatory elements indicated their diverse functions. The differential expression of various TaACA and TaECA genes during developmental stages suggested their roles in growth and development. The modulated expression during heat, drought, salt and biotic stresses along with the occurrence of various stress specific cis-regulatory elements suggested their association with stress response. Interaction of these genes with numerous development and stress related genes indicated their decisive role in various biological processes and signaling.

CONCLUSION: T. aestivum genome consisted of a maximum of 42 P-type II Ca 2+ ATPase genes, derived from each A, B and D sub-genome. These genes may play diverse functions during plant growth and development. They may also be involved in signalling during abiotic and biotic stresses. The present study provides a comprehensive insight into the role of P-type II Ca 2+ ATPase genes in T. aestivum. However, the specific function of each gene needs to be established, which could be utilized in future crop improvement programs.}, } @article {pmid29792162, year = {2018}, author = {Ahuja, G and Reichel, V and Kowatschew, D and Syed, AS and Kotagiri, AK and Oka, Y and Weth, F and Korsching, SI}, title = {Overlapping but distinct topology for zebrafish V2R-like olfactory receptors reminiscent of odorant receptor spatial expression zones.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {383}, pmid = {29792162}, issn = {1471-2164}, support = {1046/7-1//German Science foundation/ ; }, mesh = {Animals ; *Gene Expression Profiling ; Receptors, Odorant/*genetics ; Smell/genetics ; Zebrafish/*genetics/physiology ; Zebrafish Proteins/*genetics ; }, abstract = {BACKGROUND: The sense of smell is unrivaled in terms of molecular complexity of its input channels. Even zebrafish, a model vertebrate system in many research fields including olfaction, possesses several hundred different olfactory receptor genes, organized in four different gene families. For one of these families, the initially discovered odorant receptors proper, segregation of expression into distinct spatial subdomains within a common sensory surface has been observed both in teleost fish and in mammals. However, for the remaining three families, little to nothing was known about their spatial coding logic. Here we wished to investigate, whether the principle of spatial segregation observed for odorant receptors extends to another olfactory receptor family, the V2R-related OlfC genes. Furthermore we thought to examine, how expression of OlfC genes is integrated into expression zones of odorant receptor genes, which in fish share a single sensory surface with OlfC genes.

RESULTS: To select representative genes, we performed a comprehensive phylogenetic study of the zebrafish OlfC family, which identified a novel OlfC gene, reduced the number of pseudogenes to 1, and brought the total family size to 60 intact OlfC receptors. We analyzed the spatial pattern of OlfC-expressing cells for seven representative receptors in three dimensions (height within the epithelial layer, horizontal distance from the center of the olfactory organ, and height within the olfactory organ). We report non-random distributions of labeled neurons for all OlfC genes analysed. Distributions for sparsely expressed OlfC genes are significantly different from each other in nearly all cases, broad overlap notwithstanding. For two of the three coordinates analyzed, OlfC expression zones are intercalated with those of odorant receptor zones, whereas in the third dimension some segregation is observed.

CONCLUSION: Our results show that V2R-related OlfC genes follow the same spatial logic of expression as odorant receptors and their expression zones intermingle with those of odorant receptor genes. Thus, distinctly different expression zones for individual receptor genes constitute a general feature shared by teleost and tetrapod V2R/OlfC and odorant receptor families alike.}, } @article {pmid29792161, year = {2018}, author = {Temple, MD}, title = {A website to identify shared genes in Saccharomyces cerevisiae homozygous deletion library screens.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {179}, pmid = {29792161}, issn = {1471-2105}, abstract = {BACKGROUND: The homozygous yeast deletion library includes approximately 4800 diploid strains each containing one deleted non-essential gene. Hundreds of publications have arisen through experimentation using this genome-wide biological resource. As part of this work over 677 genesets have been collated from these experiments representing the phenotypic responses of the library to a diverse set of chemical and physical challenges.

DESCRIPTION: A website called the Saccharomyces cerevisiae Homozygous Deletion Library Tools (ScHo DeLiTo-96) has been developed with the primary goal of browsing and identifying genes shared between these responsive phenotypes (available at yeastdb.org). Geneset comparisons have been performed for each phenotype against all others to identify common genes. Genesets and other curated information are stored in a relational database and a website interface allows users to query and browse the data in an intuitive way to reveal commonality between selected phenotypic responses. The most commonly occurring genes in all of the stored phenotypes are highly over-represented in the GO slim term "cellular ion homeostasis" indicating that genes shared between phenotypes may highlight a common cellular response. Additionally, user derived genesets can be uploaded and intersected against the stored data to reveal common responses which may otherwise have been obscure.

CONCLUSION: These tools provide a simple method to perform niche enquiries between datasets derived from the yeast deletion library.}, } @article {pmid29792160, year = {2018}, author = {Fang, L and Hu, J and Wang, D and Wang, K}, title = {NextSV: a meta-caller for structural variants from low-coverage long-read sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {180}, pmid = {29792160}, issn = {1471-2105}, abstract = {BACKGROUND: Structural variants (SVs) in human genomes are implicated in a variety of human diseases. Long-read sequencing delivers much longer read lengths than short-read sequencing and may greatly improve SV detection. However, due to the relatively high cost of long-read sequencing, it is unclear what coverage is needed and how to optimally use the aligners and SV callers.

RESULTS: In this study, we developed NextSV, a meta-caller to perform SV calling from low coverage long-read sequencing data. NextSV integrates three aligners and three SV callers and generates two integrated call sets (sensitive/stringent) for different analysis purposes. We evaluated SV calling performance of NextSV under different PacBio coverages on two personal genomes, NA12878 and HX1. Our results showed that, compared with running any single SV caller, NextSV stringent call set had higher precision and balanced accuracy (F1 score) while NextSV sensitive call set had a higher recall. At 10X coverage, the recall of NextSV sensitive call set was 93.5 to 94.1% for deletions and 87.9 to 93.2% for insertions, indicating that ~10X coverage might be an optimal coverage to use in practice, considering the balance between the sequencing costs and the recall rates. We further evaluated the Mendelian errors on an Ashkenazi Jewish trio dataset.

CONCLUSIONS: Our results provide useful guidelines for SV detection from low coverage whole-genome PacBio data and we expect that NextSV will facilitate the analysis of SVs on long-read sequencing data.}, } @article {pmid29792159, year = {2018}, author = {Lu, GA and Zhao, Y and Liufu, Z and Wu, CI}, title = {On the possibility of death of new genes - evidence from the deletion of de novo microRNAs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {388}, pmid = {29792159}, issn = {1471-2164}, support = {31730046//National Natural Science Foundation of China/ ; 33000-18821105//985 Project/ ; 2014CB542006//National Basic Research Program (973 Program) of China/ ; }, mesh = {Animals ; Drosophila melanogaster/genetics/physiology ; *Evolution, Molecular ; Fertility/genetics ; *Gene Deletion ; Genomics ; Male ; Meiosis/genetics ; MicroRNAs/*genetics ; }, abstract = {BACKGROUND: New genes are constantly formed, sometimes from non-genic sequences, creating what is referred to as de novo genes. Since the total number of genes remains relatively steady, gene deaths likely balance out new births. In metazoan genomes, microRNAs (miRs) genes, small and non-coding, account for the bulk of functional de novo genes and are particularly suited to the investigation of gene death.

RESULTS: In this study, we discover a Drosophila-specific de novo miRNA (mir-977) that may be facing impending death. Strikingly, after this testis-specific gene is deleted from D. melanogaster, most components of male fitness increase, rather than decrease as had been expected. These components include male viability, fertility and males' ability to repress female re-mating. Given that mir-977 has a negative fitness effect in D. melanogaster, this de novo gene with an adaptive history for over 60 Myrs may be facing elimination. In some other species where mir-977 is not found, gene death may have already happened.

CONCLUSION: The surprising result suggests that de novo genes, constantly rising and falling during evolution, may often be transiently adaptive and then purged from the genome.}, } @article {pmid29792158, year = {2018}, author = {Omari, S and Kamenir, Y and Benichou, JIC and Pariente, S and Sela, H and Perl-Treves, R}, title = {Landraces of snake melon, an ancient Middle Eastern crop, reveal extensive morphological and DNA diversity for potential genetic improvement.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {34}, pmid = {29792158}, issn = {1471-2156}, support = {TA-MOU-12-M32-016//Middle East Regional Cooperation - US Agency for International Development/ ; }, abstract = {BACKGROUND: Snake melon (Cucumis melo var. flexuosus, "Faqqous") is a traditional and ancient vegetable in the Mediterranean area. A collection of landraces from 42 grower fields in Israel and Palestinian territories was grown and characterized in a "Common Garden" rain-fed experiment, at the morphological-horticultural and molecular level using seq-DArT markers.

RESULTS: The different landraces ("populations") showed extensive variation in morphology and quantitative traits such as yield and femaleness, and clustered into four horticultural varieties. Yield was assessed by five harvests along the season, with middle harvests producing the highest yields. Yield correlated with early vigor, and with femaleness, but not with late vigor. At the molecular level, 2784 SNP were produced and > 90% were mapped to the melon genome. Populations were very polymorphic (46-72% of the markers biallelic in a 4 individuals sample), and observed heterozygosity was higher than the expected, suggesting gene flow among populations and extensive cross pollination among individuals in the field. Genetic distances between landraces were significantly correlated with the geographical distance between collecting sites, and with long term March precipitation average; variation in yield correlated with April temperature maxima.

CONCLUSIONS: The extensive variation suggests that selection of local snake melon could result in yield improvement. Correlations between traits and climatic variables could suggest local adaptation of landraces to the diverse environment in which they evolved. This study stresses the importance of preserving this germplasm, and its potential for breeding better snake melons as an heirloom crop in our region.}, } @article {pmid29792157, year = {2018}, author = {Yum, SY and Lee, SJ and Park, SG and Shin, IG and Hahn, SE and Choi, WJ and Kim, HS and Kim, HJ and Bae, SH and Lee, JH and Moon, JY and Lee, WS and Lee, JH and Lee, CI and Kim, SJ and Jang, G}, title = {Long-term health and germline transmission in transgenic cattle following transposon-mediated gene transfer.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {387}, pmid = {29792157}, issn = {1471-2164}, support = {109023-05-5-CG000//Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries/ ; 2017R1A2B3004972//National Research Foundation of Korea/ ; }, mesh = {Animals ; Animals, Genetically Modified ; Cattle ; Female ; *Gene Transfer Techniques ; *Health ; Male ; Ovum/*metabolism ; Spermatozoa/*metabolism ; Transgenes/genetics ; Transposases/*genetics ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Transposon-mediated, non-viral gene delivery is a powerful tool for generating stable cell lines and transgenic animals. However, as multi-copy insertion is the preferred integration pattern, there is the potential for uncontrolled changes in endogenous gene expression and detrimental effects in cells or animals. Our group has previously reported on the generation of several transgenic cattle by using microinjection of the Sleeping Beauty (SB) and PiggyBac (PB) transposons and seeks to explore the long-term effects of this technology on cattle.

RESULTS: Transgenic cattle, one female (SNU-SB-1) and one male (SNU-PB-1), reached over 36 months of age with no significant health issues and normal blood parameters. The detection of transgene integration and fluorescent signal in oocytes and sperm suggested the capacity for germline transmission in both of the founder animals. After natural breeding, the founder transgenic cow delivered a male calf and secreted milk containing fluorescent transgenic proteins. The calf expressed green fluorescent protein in primary cells from ear skin, with no significant change in overall genomic stability and blood parameters. Three sites of transgene integration were identified by next-generation sequencing of the calf's genome.

CONCLUSIONS: Overall, these data demonstrate that transposon-mediated transgenesis can be applied to cattle without being detrimental to their long-term genomic stability or general health. We further suggest that this technology may be usefully applied in other fields, such as the generation of transgenic animal models.}, } @article {pmid29791058, year = {2018}, author = {Dubuc-Messier, G and Caro, SP and Perrier, C and van Oers, K and Réale, D and Charmantier, A}, title = {Gene flow does not prevent personality and morphological differentiation between two blue tit populations.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1127-1137}, doi = {10.1111/jeb.13291}, pmid = {29791058}, issn = {1420-9101}, abstract = {Understanding the causes and consequences of population phenotypic divergence is a central goal in ecology and evolution. Phenotypic divergence among populations can result from genetic divergence, phenotypic plasticity or a combination of the two. However, few studies have deciphered these mechanisms for populations geographically close and connected by gene flow, especially in the case of personality traits. In this study, we used a common garden experiment to explore the genetic basis of the phenotypic divergence observed between two blue tit (Cyanistes caeruleus) populations inhabiting contrasting habitats separated by 25 km, for two personality traits (exploration speed and handling aggression), one physiological trait (heart rate during restraint) and two morphological traits (tarsus length and body mass). Blue tit nestlings were removed from their population and raised in a common garden for up to 5 years. We then compared adult phenotypes between the two populations, as well as trait-specific Qst and Fst . Our results revealed differences between populations similar to those found in the wild, suggesting a genetic divergence for all traits. Qst -Fst comparisons revealed that the trait divergences likely result from dissimilar selection patterns rather than from genetic drift. Our study is one of the first to report a Qst -Fst comparison for personality traits and adds to the growing body of evidence that population genetic divergence is possible at a small scale for a variety of traits including behavioural traits.}, } @article {pmid29791044, year = {2018}, author = {Vega-Trejo, R and Kruuk, LEB and Jennions, MD and Head, ML}, title = {What happens to offspring when parents are inbred, old or had a poor start in life? Evidence for sex-specific parental effects.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1138-1151}, doi = {10.1111/jeb.13292}, pmid = {29791044}, issn = {1420-9101}, abstract = {Parental effects on offspring performance have been attributed to many factors such as parental age, size and condition. However, we know little about how these different parental characteristics interact to determine parental effects, or the extent to which their effect on offspring depends on either the sex of the parent or that of the offspring. Here we experimentally tested for effects of variation in parents' early diet and inbreeding levels, as well as effects of parental age, and for potential interactive effects of these three factors on key aspects of offspring development in the mosquitofish (Gambusia holbrooki). Older mothers produced offspring that were significantly smaller at birth. This negative effect of maternal age on offspring size was still evident at maturation as older mothers had smaller daughters, but not smaller sons. The daughters of older mothers did, however, reach maturity sooner. Paternal age did not affect offspring body size, but it had a complex effect on their sons' relative genital size. When initially raised on a food-restricted diet, older fathers sired sons with relatively smaller genitalia, but when fathers were initially raised on a control diet their sons had relatively larger genitalia. The inbreeding status of mothers and fathers had no significant effects on any of the measured offspring traits. Our results indicate that the manifestation of parental effects can be complex. It can vary with both parent and offspring sex; can change over an offspring's life; and is sometimes evident as an interaction between different parental traits. Understanding this complexity will be important to predict the role of parental effects in adaptation.}, } @article {pmid29790980, year = {2018}, author = {Chen, ZH and Zhang, M and Lv, FH and Ren, X and Li, WR and Liu, MJ and Nam, K and Bruford, MW and Li, MH}, title = {Contrasting Patterns of Genomic Diversity Reveal Accelerated Genetic Drift but Reduced Directional Selection on X-Chromosome in Wild and Domestic Sheep Species.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1282-1297}, pmid = {29790980}, issn = {1759-6653}, mesh = {Animals ; Animals, Wild ; Chromosomes, Mammalian/genetics ; Female ; Genes, X-Linked/genetics ; *Genetic Drift ; *Genetic Variation ; Genetics, Population ; Genomics ; Humans ; Male ; Molecular Sequence Data ; Polymorphism, Single Nucleotide ; Pseudoautosomal Regions ; *Selection, Genetic ; Sheep/*genetics ; Sheep, Domestic/genetics ; X Chromosome/*genetics ; }, abstract = {Analyses of genomic diversity along the X chromosome and of its correlation with autosomal diversity can facilitate understanding of evolutionary forces in shaping sex-linked genomic architecture. Strong selective sweeps and accelerated genetic drift on the X-chromosome have been inferred in primates and other model species, but no such insight has yet been gained in domestic animals compared with their wild relatives. Here, we analyzed X-chromosome variability in a large ovine data set, including a BeadChip array for 943 ewes from the world's sheep populations and 110 whole genomes of wild and domestic sheep. Analyzing whole-genome sequences, we observed a substantially reduced X-to-autosome diversity ratio (∼0.6) compared with the value expected under a neutral model (0.75). In particular, one large X-linked segment (43.05-79.25 Mb) was found to show extremely low diversity, most likely due to a high density of coding genes, featuring highly conserved regions. In general, we observed higher nucleotide diversity on the autosomes, but a flat diversity gradient in X-linked segments, as a function of increasing distance from the nearest genes, leading to a decreased X: autosome (X/A) diversity ratio and contrasting to the positive correlation detected in primates and other model animals. Our evidence suggests that accelerated genetic drift but reduced directional selection on X chromosome, as well as sex-biased demographic events, explain low X-chromosome diversity in sheep species. The distinct patterns of X-linked and X/A diversity we observed between Middle Eastern and non-Middle Eastern sheep populations can be explained by multiple migrations, selection, and admixture during the domestic sheep's recent postdomestication demographic expansion, coupled with natural selection for adaptation to new environments. In addition, we identify important novel genes involved in abnormal behavioral phenotypes, metabolism, and immunity, under selection on the sheep X-chromosome.}, } @article {pmid29790946, year = {2018}, author = {Villageliú, DN and Rasmussen, S and Lyte, M}, title = {A microbial endocrinology-based simulated small intestinal medium for the evaluation of neurochemical production by gut microbiota.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy096}, pmid = {29790946}, issn = {1574-6941}, abstract = {Microbial endocrinology represents the union of microbiology and neurobiology and is concerned with the ability of neurochemicals to serve as an evolutionary-based language between host and microbiota in health and disease. The recognition that microorganisms produce, modify and respond to the same neurochemicals utilized in the various signaling pathways of their mammalian hosts is increasingly being recognized as a mechanism by which the host and microbiota may interact to influence the progression of infectious disease as well as influence behavior through the microbiota-gut-brain axis. While the capacity for bacteria to produce neurochemicals has been recognized for decades, the degree to which this occurs in the environment of the gastrointestinal tract is still poorly understood. By combining techniques used in analytic chemistry, food science and environmental microbiology, a novel culture-based method was developed which generates a medium utilizing animal feed which resembles the contents of the small intestine. The usage of this medium allows for the in vitro growth of bacteria native to the gastrointestinal tract in an environment that is reflective of the small-intestinal host-based milieu. We describe a detailed protocol for the preparation of this medium and the quantification of neurochemicals by microorganisms grown therein. Catecholamines including dopamine and its precursor L-3,4-dihydroxyphenalanine (L-DOPA) as well as biogenic amines including tyramine and its precursor tyrosine, serve as prototypical examples of neurochemicals that are quantifiable with the methods described herein.}, } @article {pmid29790926, year = {2018}, author = {Zhou, Z and Pan, J and Wang, F and Gu, JD and Li, M}, title = {Bathyarchaeota: globally distributed metabolic generalists in anoxic environments.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {639-655}, doi = {10.1093/femsre/fuy023}, pmid = {29790926}, issn = {1574-6976}, mesh = {Anaerobiosis ; Archaea/metabolism/*physiology ; *Biological Evolution ; Carbon Cycle/genetics ; *Environmental Microbiology ; Genome, Archaeal/genetics ; }, abstract = {Bathyarchaeota, formerly known as the Miscellaneous Crenarchaeotal Group, is a phylum of global generalists that are widespread in anoxic sediments, which host relatively high abundance archaeal communities. Until now, 25 subgroups have been identified in the Bathyarchaeota. The distinct bathyarchaeotal subgroups diverged to adapt to marine and freshwater environments. Based on the physiological and genomic evidence, acetyl-coenzyme A-centralized heterotrophic pathways of energy conservation have been proposed to function in Bathyarchaeota; these microbes are able to anaerobically utilize (i) detrital proteins, (ii) polymeric carbohydrates, (iii) fatty acids/aromatic compounds, (iv) methane (or short chain alkane) and methylated compounds, and/or (v) potentially other organic matter. Furthermore, bathyarchaeotal members have wide metabolic capabilities, including acetogenesis, methane metabolism, and dissimilatory nitrogen and sulfur reduction, and they also have potential interactions with anaerobic methane-oxidizing archaea, acetoclastic methanogens and heterotrophic bacteria. These results have not only demonstrated multiple and important ecological functions of this archaeal phylum, but also paved the way for a detailed understanding of the evolution and metabolism of archaea as such. This review summarizes the recent findings pertaining to the ecological, physiological and genomic aspects of Bathyarchaeota, highlighting the vital role of this phylum in global carbon cycling.}, } @article {pmid29790924, year = {2018}, author = {Hiyoshi, H and Tiffany, CR and Bronner, DN and Bäumler, AJ}, title = {Typhoidal Salmonella serovars: ecological opportunity and the evolution of a new pathovar.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {527-541}, doi = {10.1093/femsre/fuy024}, pmid = {29790924}, issn = {1574-6976}, mesh = {Animals ; *Biological Evolution ; Host-Pathogen Interactions/*physiology ; Humans ; Salmonella/pathogenicity/*physiology ; Serogroup ; Typhoid Fever/microbiology ; }, abstract = {Typhoid and paratyphoid fever are severe systemic infections caused by human-adapted typhoidal Salmonella serovars that are indistinguishable in their clinical presentation, but differ from human gastroenteritis caused by zoonotic non-typhoidal Salmonella serovars. Typhoidal Salmonella serovars evolved from ancestral gastrointestinal pathogens through genetic changes that supported a change in pathogen ecology. Typhoidal Salmonella serovars share virulence properties that were acquired through convergent evolution and therefore this group is not defined by the presence of shared virulence genes that are absent from non-typhoidal Salmonella serovars. One feature distinguishing typhoidal Salmonella serovars from gastrointestinal pathogens is their ability to avert the respiratory burst of neutrophils. Furthermore, typhoidal Salmonella serovars possess several mechanisms to moderate intestinal inflammation, which are absent from non-typhoidal Salmonella serovars. Collectively, these shared virulence mechanisms enable typhoidal Salmonella serovars to breach an intact mucosal barrier and reach the gall bladder, a new ecological niche that is important because chronic gall bladder carriage promotes disease transmission. Thus, the morbidity and mortality resulting from the severe systemic infection that enables typhoidal Salmonella serovars to reach the gall bladder is coupled to their capacity for infectious transmission, which is the principal driving force of natural selection directing the emergence of this pathovar.}, } @article {pmid29790846, year = {2018}, author = {Amoozegar, MA and Shahinpei, A and Makzum, S and Rafieyan, S and Moshtaghi Nikou, M and Spröer, C and Ventosa, A}, title = {Salipaludibacillus halalkaliphilus sp. nov., a moderately haloalkaliphilic bacterium from a coastal-marine wetland.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2214-2219}, doi = {10.1099/ijsem.0.002814}, pmid = {29790846}, issn = {1466-5034}, mesh = {Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Iran ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spores, Bacterial/genetics ; Vitamin K 2/analogs & derivatives/chemistry ; *Wetlands ; }, abstract = {A Gram-stain-positive, endospore-forming rod-shaped non-motile, moderately halophilic and alkaliphilic bacterium, strain GASy1T, was isolated from a water sample from Gomishan, a marine wetland in Iran. GASy1T required at least 0.5 % (w/v) NaCl for growth and was able to grow at NaCl concentrations of up to 15 % (w/v), with optimum growth occurring at 5 % (w/v) NaCl. The optimum pH and temperature for growth were pH 8.5-9.0 and 30 °C, respectively, while it was able to grow over a pH range and a temperature range of 7.5-10.0 and 4-40 °C, respectively. GASy1T was catalase-positive and oxidase-negative. Analysis of 16S rRNA gene sequences revealed that GASy1T represents a member of the genus Salipaludibacillus, family Bacillaceae within the order Bacillales, showing 97.4 % sequence similarity to Salipaludibacillus neizhouensis JSM 071004T, and 96.2 and 95.7 % sequence similarity to Salipaludibacillus agaradhaerens AC 13T and Salipaludibacillus aurantiacus S9T, respectively. The DNA G+C content of GASy1T was 38.8 mol%. The polar lipids of the strain were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine and two unidentified phospholipids and its major cellular fatty acids were anteiso-C15 : 0, C16 : 0 and iso-C15 : 0. The isoprenoid quinone was MK-7. DNA-DNA hybridization experiments revealed a low level of relatedness between GASy1T and Salipaludibacillus neizhouensis IBRC-M 10892T (18 %). On the basis of a combination of phenotypic, chemotaxonomic and phylogenetic features, GASy1T represents a novel species of the genus Salipaludibacillus, for which the name Salipaludibacillus halalkaliphilus sp. nov. is proposed. The type strain of Salipaludibacillus halalkaliphilus is GASy1T (=IBRC M 10902T=LMG 28385T).}, } @article {pmid29790249, year = {2018}, author = {Tikhodeyev, ON}, title = {The mechanisms of epigenetic inheritance: how diverse are they?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1987-2005}, doi = {10.1111/brv.12429}, pmid = {29790249}, issn = {1469-185X}, abstract = {Although epigenetic inheritance (EI) is a rapidly growing field of modern biology, it still has no clear place in fundamental genetic concepts which are traditionally based on the hereditary role of DNA. Moreover, not all mechanisms of EI attract the same attention, with most studies focused on DNA methylation, histone modification, RNA interference and amyloid prionization, but relatively few considering other mechanisms such as stable inhibition of plastid translation. Herein, we discuss all known and some hypothetical mechanisms that can underlie the stable inheritance of phenotypically distinct hereditary factors that lack differences in DNA sequence. These mechanisms include (i) regulation of transcription by DNA methylation, histone modifications, and transcription factors, (ii) RNA splicing, (iii) RNA-mediated post-transcriptional silencing, (iv) organellar translation, (v) protein processing by truncation, (vi) post-translational chemical modifications, (vii) protein folding, and (viii) homologous and non-homologous protein interactions. The breadth of this list suggests that any or almost any regulatory mechanism that participates in gene expression or gene-product functioning, under certain circumstances, may produce EI. Although the modes of EI are highly variable, in many epigenetic systems, stable allelic variants can be distinguished. Irrespective of their nature, all such alleles have an underlying similarity: each is a bimodular hereditary unit, whose features depend on (i) a certain epigenetic mark (epigenetic determinant) in the DNA sequence or its product, and (ii) the DNA sequence itself (DNA determinant; if this is absent, the epigenetic allele fails to perpetuate). Thus, stable allelic epigenetic inheritance (SAEI) does not contradict the hereditary role of DNA, but involves additional molecular mechanisms with no or almost no limitations to their variety.}, } @article {pmid29790246, year = {2018}, author = {Roos, S and Smart, J and Gibbons, DW and Wilson, JD}, title = {A review of predation as a limiting factor for bird populations in mesopredator-rich landscapes: a case study of the UK.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1915-1937}, doi = {10.1111/brv.12426}, pmid = {29790246}, issn = {1469-185X}, abstract = {The impact of increasing vertebrate predator numbers on bird populations is widely debated among the general public, game managers and conservationists across Europe. However, there are few systematic reviews of whether predation limits the population sizes of European bird species. Views on the impacts of predation are particularly polarised in the UK, probably because the UK has a globally exceptional culture of intensive, high-yield gamebird management where predator removal is the norm. In addition, most apex predators have been exterminated or much depleted in numbers, contributing to a widely held perception that the UK has high numbers of mesopredators. This has resulted in many high-quality studies of mesopredator impacts over several decades. Here we present results from a systematic review of predator trends and abundance, and assess whether predation limits the population sizes of 90 bird species in the UK. Our results confirm that the generalist predators Red Fox (Vulpes vulpes) and Crows (Corvus corone and C. cornix) occur at high densities in the UK compared with other European countries. In addition, some avian and mammalian predators have increased numerically in the UK during recent decades. Despite these high and increasing densities of predators, we found little evidence that predation limits populations of pigeons, woodpeckers and passerines, whereas evidence suggests that ground-nesting seabirds, waders and gamebirds can be limited by predation. Using life-history characteristics of prey species, we found that mainly long-lived species with high adult survival and late onset of breeding were limited by predation. Single-brooded species were also more likely to be limited by predation than multi-brooded species. Predators that depredate prey species during all life stages (i.e. from nest to adult stages) limited prey numbers more than predators that depredated only specific life stages (e.g. solely during the nest phase). The Red Fox and non-native mammals (e.g. the American Mink Neovison vison) were frequently identified as numerically limiting their prey species. Our review has identified predator-prey interactions that are particularly likely to result in population declines of prey species. In the short term, traditional predator-management techniques (e.g. lethal control or fencing to reduce predation by a small number of predator species) could be used to protect these vulnerable species. However, as these techniques are costly and time-consuming, we advocate that future research should identify land-use practices and landscape configurations that would reduce predator numbers and predation rates.}, } @article {pmid29789973, year = {2018}, author = {Nakashima, K and Abe, J and Kanazawa, A}, title = {Chromosomal distribution of soybean retrotransposon SORE-1 suggests its recent preferential insertion into euchromatic regions.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {3}, pages = {199-210}, pmid = {29789973}, issn = {1573-6849}, support = {17H03743//Japan Society for the Promotion of Science/International ; }, mesh = {Chromosomes, Plant/*genetics/metabolism ; Euchromatin/*genetics/metabolism ; Retroelements/*physiology ; Soybeans/*genetics/metabolism ; Terminal Repeat Sequences/*physiology ; }, abstract = {Retrotransposons constitute a large portion of plant genomes. The chromosomal distribution of a wide variety of retrotransposons has been analyzed using genome sequencing data in several plants, but the evolutionary profile of transposition has been characterized for a limited number of retrotransposon families. Here, we characterized 96 elements of the SORE-1 family of soybean retrotransposons using genome sequencing data. Insertion time of each SORE-1 element into the genome was estimated on the basis of sequence differences between the 5' and 3' long terminal repeats (LTRs). Combining this estimation with information on the chromosomal location of these elements, we found that the insertion of the existing SORE-1 into gene-rich chromosome arms occurred on average more recently than that into gene-poor pericentromeric regions. In addition, both the number of insertions and the proportion of insertions into chromosome arms profoundly increased after 1 million years ago. Solo LTRs were detected in these regions at a similar frequency, suggesting that elimination of SORE-1 via unequal homologous recombination was unbiased. Taken together, these results suggest the preference of a recent insertion of SORE-1 into chromosome arms comprising euchromatic regions. This notion is contrary to an earlier view deduced from an overall profiling of soybean retrotransposons and suggests that the pattern of chromosomal distribution can be more diverse than previously thought between different families of retrotransposons.}, } @article {pmid29789752, year = {2018}, author = {}, title = {Science needs clarity on Europe's data-protection law.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {467}, doi = {10.1038/d41586-018-05220-y}, pmid = {29789752}, issn = {1476-4687}, mesh = {*Computer Security ; Europe ; }, } @article {pmid29789751, year = {2018}, author = {Oreskes, N}, title = {Beware: transparency rule is a Trojan Horse.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {469}, doi = {10.1038/d41586-018-05207-9}, pmid = {29789751}, issn = {1476-4687}, mesh = {Air Pollution/legislation & jurisprudence/prevention & control ; Climate Change/statistics & numerical data ; Conflict of Interest ; Humans ; Lobbying ; Ozone ; Reproducibility of Results ; Tobacco Smoke Pollution/legislation & jurisprudence ; Uncertainty ; United States ; United States Environmental Protection Agency/*ethics/legislation & jurisprudence/*standards ; }, } @article {pmid29789750, year = {2018}, author = {Rochmyaningsih, D}, title = {Indonesian plan to clamp down on foreign scientists draws protest.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {476}, doi = {10.1038/d41586-018-05001-7}, pmid = {29789750}, issn = {1476-4687}, mesh = {*Federal Government ; Foreign Professional Personnel/*legislation & jurisprudence ; Indonesia ; *International Cooperation ; *Research/legislation & jurisprudence/organization & administration ; Research Personnel/*legislation & jurisprudence/organization & administration ; Workforce ; }, } @article {pmid29789749, year = {2018}, author = {Nagendra, H}, title = {The global south is rich in sustainability lessons that students deserve to hear.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {485-488}, doi = {10.1038/d41586-018-05210-0}, pmid = {29789749}, issn = {1476-4687}, mesh = {Animals ; Biodiversity ; *Climate Change ; Conservation of Energy Resources ; Conservation of Natural Resources/*methods/trends ; Curriculum ; *Developed Countries ; *Developing Countries ; Ecology/*education/*methods/trends ; *Human Activities ; Humans ; India ; Population Growth ; Water Supply ; Workforce ; }, } @article {pmid29789748, year = {2018}, author = {Landhuis, E}, title = {Single-cell approaches to immune profiling.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {595-597}, doi = {10.1038/d41586-018-05214-w}, pmid = {29789748}, issn = {1476-4687}, mesh = {Antibodies/analysis/immunology/metabolism ; DNA/analysis ; Flow Cytometry ; Humans ; Leukocytes/chemistry/*immunology/*metabolism ; Mass Spectrometry ; Receptors, Antigen, T-Cell/analysis/immunology/metabolism ; Single-Cell Analysis/*methods ; }, } @article {pmid29789747, year = {2018}, author = {Gewin, V}, title = {An ultralight way to manipulate brain signals.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {601}, doi = {10.1038/d41586-018-05216-8}, pmid = {29789747}, issn = {1476-4687}, } @article {pmid29789746, year = {2018}, author = {Castelvecchi, D}, title = {Chinese satellite launch kicks off ambitious mission to Moon's far side.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {478-479}, doi = {10.1038/d41586-018-05231-9}, pmid = {29789746}, issn = {1476-4687}, mesh = {Animals ; Astronauts ; Astronomy ; Bombyx/physiology ; China ; *Darkness ; Extraterrestrial Environment/*chemistry ; Humans ; International Cooperation ; *Moon ; Seeds/growth & development/metabolism ; *Space Flight ; *Spacecraft ; }, } @article {pmid29789745, year = {2018}, author = {Schlenker, W and Auffhammer, M}, title = {The cost of a warming climate.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {498-499}, doi = {10.1038/d41586-018-05198-7}, pmid = {29789745}, issn = {1476-4687}, mesh = {*Climate ; *Climate Change ; Global Warming ; }, } @article {pmid29789744, year = {2018}, author = {Kwok, R}, title = {How to fit in when you join a lab abroad.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {599-601}, doi = {10.1038/d41586-018-05215-9}, pmid = {29789744}, issn = {1476-4687}, mesh = {Communication ; *Cross-Cultural Comparison ; *Cultural Competency ; Electronic Mail ; Emigrants and Immigrants/*psychology ; Foreign Professional Personnel/*psychology ; *Laboratories ; Leadership ; Research Personnel/*psychology ; Social Behavior ; Stereotyping ; Workforce ; Workplace/*psychology ; }, } @article {pmid29789743, year = {2018}, author = {McElreath, R}, title = {Sizing up human brain evolution.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {496-497}, doi = {10.1038/d41586-018-05197-8}, pmid = {29789743}, issn = {1476-4687}, mesh = {*Anthropology ; *Biological Evolution ; Brain ; Humans ; }, } @article {pmid29789742, year = {2018}, author = {Song, JCW}, title = {Plasmon propagation pushed to the limit.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {501-502}, doi = {10.1038/d41586-018-05190-1}, pmid = {29789742}, issn = {1476-4687}, } @article {pmid29789741, year = {2018}, author = {Hessels, J}, title = {Pulsars seen through a new lens.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {494-495}, doi = {10.1038/d41586-018-05185-y}, pmid = {29789741}, issn = {1476-4687}, } @article {pmid29789739, year = {2018}, author = {Tao, J and Ding, C and Ho, YS}, title = {Publish translations of the best Chinese papers.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {492}, doi = {10.1038/d41586-018-05235-5}, pmid = {29789739}, issn = {1476-4687}, mesh = {China ; Humans ; Periodicals as Topic ; *Publishing ; *Translations ; }, } @article {pmid29789738, year = {2018}, author = {Espejo, W and Galbán-Malagón, C and Chiang Merimoyu, G}, title = {Risks from technology-critical metals after extraction.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {492}, doi = {10.1038/d41586-018-05234-6}, pmid = {29789738}, issn = {1476-4687}, } @article {pmid29789737, year = {2018}, author = {Gutiérrez, JS and Navedo, JG and Soriano-Redondo, A}, title = {Chilean Atacama site imperilled by lithium mining.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {492}, doi = {10.1038/d41586-018-05233-7}, pmid = {29789737}, issn = {1476-4687}, mesh = {Animals ; Birds/physiology ; Chile ; Cyanobacteria/isolation & purification ; *Ecosystem ; Humans ; Lithium/*isolation & purification ; Mining/*legislation & jurisprudence ; Water Microbiology ; Water Pollutants/analysis ; }, } @article {pmid29789736, year = {2018}, author = {Ahmadia, G}, title = {Recruit young scientists and local talent to safeguard coral reefs.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {492}, doi = {10.1038/d41586-018-05221-x}, pmid = {29789736}, issn = {1476-4687}, mesh = {Animals ; *Anthozoa ; Conservation of Natural Resources/methods/*trends ; *Coral Reefs ; Fisheries ; *Personnel Selection ; Research Personnel/*supply & distribution ; }, } @article {pmid29789734, year = {2018}, author = {}, title = {Customers put off electric cars … by electric-car sales staff.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {468}, doi = {10.1038/d41586-018-05218-6}, pmid = {29789734}, issn = {1476-4687}, } @article {pmid29789733, year = {2018}, author = {}, title = {Why your feet slip and slide on ice.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {470-471}, doi = {10.1038/d41586-018-05225-7}, pmid = {29789733}, issn = {1476-4687}, } @article {pmid29789732, year = {2018}, author = {Check Hayden, E}, title = {Experimental drugs poised for use in Ebola outbreak.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {475-476}, doi = {10.1038/d41586-018-05205-x}, pmid = {29789732}, issn = {1476-4687}, mesh = {Alanine/analogs & derivatives/therapeutic use ; Amides/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; Congo/epidemiology ; Disease Outbreaks/*prevention & control ; Drugs, Investigational/administration & dosage/pharmacology/*therapeutic use ; Ebola Vaccines/immunology/therapeutic use ; Ebolavirus/drug effects/immunology ; Hemorrhagic Fever, Ebola/*drug therapy/epidemiology/mortality/*prevention & control ; Humans ; Internationality ; Pyrazines/therapeutic use ; Ribonucleotides/therapeutic use ; }, } @article {pmid29789731, year = {2018}, author = {Reardon, S}, title = {Hawaii volcano eruption holds clues to predicting similar events elsewhere.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {477}, doi = {10.1038/d41586-018-05206-w}, pmid = {29789731}, issn = {1476-4687}, mesh = {Forecasting/*methods ; Hawaii ; Humans ; Volcanic Eruptions/*statistics & numerical data ; }, } @article {pmid29789730, year = {2018}, author = {}, title = {A double-pronged attack on colon tumours succeeds where one doesn't.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {471}, doi = {10.1038/d41586-018-05201-1}, pmid = {29789730}, issn = {1476-4687}, } @article {pmid29789729, year = {2018}, author = {Else, H}, title = {Europe's open-access drive escalates as university stand-offs spread.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {479-480}, doi = {10.1038/d41586-018-05191-0}, pmid = {29789729}, issn = {1476-4687}, mesh = {*Negotiating ; Open Access Publishing/economics/*trends ; *Research/economics ; Sweden ; *Universities/economics ; }, } @article {pmid29789728, year = {2018}, author = {}, title = {Why dinosaurs arranged their eggs in a doughnut shape.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {470}, doi = {10.1038/d41586-018-05192-z}, pmid = {29789728}, issn = {1476-4687}, } @article {pmid29789727, year = {2018}, author = {}, title = {Soaring overdose death rate fuels rise in organ transplantation.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {470}, doi = {10.1038/d41586-018-05194-x}, pmid = {29789727}, issn = {1476-4687}, } @article {pmid29789726, year = {2018}, author = {}, title = {Worm-eating mountain mice showcase evolution in action.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {471}, doi = {10.1038/d41586-018-05193-y}, pmid = {29789726}, issn = {1476-4687}, } @article {pmid29789725, year = {2018}, author = {}, title = {Stink bugs leave DNA footprints on produce.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {471}, doi = {10.1038/d41586-018-05184-z}, pmid = {29789725}, issn = {1476-4687}, } @article {pmid29789724, year = {2018}, author = {}, title = {A geyser spurts from one of Jupiter's icy moons.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {470}, doi = {10.1038/d41586-018-05183-0}, pmid = {29789724}, issn = {1476-4687}, } @article {pmid29789723, year = {2018}, author = {}, title = {A potential cure for the common cold.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {471}, doi = {10.1038/d41586-018-05181-2}, pmid = {29789723}, issn = {1476-4687}, } @article {pmid29789722, year = {2018}, author = {}, title = {How to tell how much wasp stings will hurt.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {471}, doi = {10.1038/d41586-018-05126-9}, pmid = {29789722}, issn = {1476-4687}, } @article {pmid29789687, year = {2018}, author = {Raymond, FL and Horvath, R and Chinnery, PF}, title = {First-line genomic diagnosis of mitochondrial disorders.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {399-400}, doi = {10.1038/s41576-018-0022-1}, pmid = {29789687}, issn = {1471-0064}, support = {MC_UP_1501/2//Medical Research Council/United Kingdom ; }, } @article {pmid29789686, year = {2018}, author = {Torkamani, A and Wineinger, NE and Topol, EJ}, title = {The personal and clinical utility of polygenic risk scores.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {9}, pages = {581-590}, doi = {10.1038/s41576-018-0018-x}, pmid = {29789686}, issn = {1471-0064}, abstract = {Initial expectations for genome-wide association studies were high, as such studies promised to rapidly transform personalized medicine with individualized disease risk predictions, prevention strategies and treatments. Early findings, however, revealed a more complex genetic architecture than was anticipated for most common diseases - complexity that seemed to limit the immediate utility of these findings. As a result, the practice of utilizing the DNA of an individual to predict disease has been judged to provide little to no useful information. Nevertheless, recent efforts have begun to demonstrate the utility of polygenic risk profiling to identify groups of individuals who could benefit from the knowledge of their probabilistic susceptibility to disease. In this context, we review the evidence supporting the personal and clinical utility of polygenic risk profiling.}, } @article {pmid29789680, year = {2018}, author = {Banerjee, S and Schlaeppi, K and van der Heijden, MGA}, title = {Keystone taxa as drivers of microbiome structure and functioning.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {9}, pages = {567-576}, doi = {10.1038/s41579-018-0024-1}, pmid = {29789680}, issn = {1740-1534}, abstract = {Microorganisms have a pivotal role in the functioning of ecosystems. Recent studies have shown that microbial communities harbour keystone taxa, which drive community composition and function irrespective of their abundance. In this Opinion article, we propose a definition of keystone taxa in microbial ecology and summarize over 200 microbial keystone taxa that have been identified in soil, plant and marine ecosystems, as well as in the human microbiome. We explore the importance of keystone taxa and keystone guilds for microbiome structure and functioning and discuss the factors that determine their distribution and activities.}, } @article {pmid29789679, year = {2018}, author = {York, A}, title = {Live cables over long distances.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {395}, doi = {10.1038/s41579-018-0034-z}, pmid = {29789679}, issn = {1740-1534}, } @article {pmid29789678, year = {2018}, author = {York, A}, title = {Dealing with the pain.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {395}, doi = {10.1038/s41579-018-0032-1}, pmid = {29789678}, issn = {1740-1534}, } @article {pmid29789677, year = {2018}, author = {York, A}, title = {Taking on the intractable.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {395}, doi = {10.1038/s41579-018-0033-0}, pmid = {29789677}, issn = {1740-1534}, } @article {pmid29789547, year = {2018}, author = {Parker, TH and Griffith, SC and Bronstein, JL and Fidler, F and Foster, S and Fraser, H and Forstmeier, W and Gurevitch, J and Koricheva, J and Seppelt, R and Tingley, MW and Nakagawa, S}, title = {Empowering peer reviewers with a checklist to improve transparency.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {929-935}, doi = {10.1038/s41559-018-0545-z}, pmid = {29789547}, issn = {2397-334X}, abstract = {Peer review is widely considered fundamental to maintaining the rigour of science, but it often fails to ensure transparency and reduce bias in published papers, and this systematically weakens the quality of published inferences. In part, this is because many reviewers are unaware of important questions to ask with respect to the soundness of the design and analyses, and the presentation of the methods and results; also some reviewers may expect others to be responsible for these tasks. We therefore present a reviewers' checklist of ten questions that address these critical components. Checklists are commonly used by practitioners of other complex tasks, and we see great potential for the wider adoption of checklists for peer review, especially to reduce bias and facilitate transparency in published papers. We expect that such checklists will be well received by many reviewers.}, } @article {pmid29789546, year = {2018}, author = {}, title = {A checklist for our community.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {913}, doi = {10.1038/s41559-018-0574-7}, pmid = {29789546}, issn = {2397-334X}, } @article {pmid29789384, year = {2018}, author = {Müller, NA and Zhang, L and Koornneef, M and Jiménez-Gómez, JM}, title = {Mutations in EID1 and LNK2 caused light-conditional clock deceleration during tomato domestication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {27}, pages = {7135-7140}, pmid = {29789384}, issn = {1091-6490}, mesh = {Circadian Clocks/*genetics ; *Domestication ; *Light ; *Lycopersicon esculentum/genetics/metabolism ; *Mutation ; Phytochrome B/genetics/metabolism ; *Trans-Activators/genetics/metabolism ; }, abstract = {Circadian period and phase of cultivated tomato (Solanum lycopersicum) were changed during domestication, likely adapting the species to its new agricultural environments. Whereas the delayed circadian phase is mainly caused by allelic variation of EID1, the genetic basis of the long circadian period has remained elusive. Here we show that a partial deletion of the clock gene LNK2 is responsible for the period lengthening in cultivated tomatoes. We use resequencing data to phylogenetically classify hundreds of tomato accessions and investigate the evolution of the eid1 and lnk2 mutations along successive domestication steps. We reveal signatures of selection across the genomic region of LNK2 and different patterns of fixation of the mutant alleles. Strikingly, LNK2 and EID1 are both involved in light input to the circadian clock, indicating that domestication specifically targeted this input pathway. In line with this, we show that the clock deceleration in the cultivated tomato is light-dependent and requires the phytochrome B1 photoreceptor. Such conditional variation in circadian rhythms may be key for latitudinal adaptation in a variety of species, including crop plants and livestock.}, } @article {pmid29789383, year = {2018}, author = {Tabib-Salazar, A and Liu, B and Barker, D and Burchell, L and Qimron, U and Matthews, SJ and Wigneshweraraj, S}, title = {T7 phage factor required for managing RpoS in Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5353-E5362}, pmid = {29789383}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 100280//Wellcome Trust/United Kingdom ; 104833//Wellcome Trust/United Kingdom ; 100958//Wellcome Trust/United Kingdom ; }, mesh = {Bacterial Proteins/*metabolism ; Bacteriophage T7/enzymology/genetics/*metabolism ; Crystallography, X-Ray ; DNA-Directed DNA Polymerase/metabolism ; DNA-Directed RNA Polymerases/*antagonists & inhibitors/metabolism ; Escherichia coli/metabolism/*virology ; Models, Molecular ; Promoter Regions, Genetic ; Protein Conformation ; Repressor Proteins/*metabolism ; Sigma Factor/*metabolism ; Transcription, Genetic ; }, abstract = {T7 development in Escherichia coli requires the inhibition of the housekeeping form of the bacterial RNA polymerase (RNAP), Eσ70, by two T7 proteins: Gp2 and Gp5.7. Although the biological role of Gp2 is well understood, that of Gp5.7 remains to be fully deciphered. Here, we present results from functional and structural analyses to reveal that Gp5.7 primarily serves to inhibit EσS, the predominant form of the RNAP in the stationary phase of growth, which accumulates in exponentially growing E. coli as a consequence of the buildup of guanosine pentaphosphate [(p)ppGpp] during T7 development. We further demonstrate a requirement of Gp5.7 for T7 development in E. coli cells in the stationary phase of growth. Our finding represents a paradigm for how some lytic phages have evolved distinct mechanisms to inhibit the bacterial transcription machinery to facilitate phage development in bacteria in the exponential and stationary phases of growth.}, } @article {pmid29789382, year = {2018}, author = {Shtanko, O and Levitov, L}, title = {Robustness and universality of surface states in Dirac materials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5908-5913}, pmid = {29789382}, issn = {1091-6490}, abstract = {Ballistically propagating topologically protected states harbor exotic transport phenomena of wide interest. Here we describe a nontopological mechanism that produces such states at the surfaces of generic Dirac materials, giving rise to propagating surface modes with energies near the bulk band crossing. The robustness of surface states originates from the unique properties of Dirac-Bloch wavefunctions which exhibit strong coupling to generic boundaries. Surface states, described by Jackiw-Rebbi-type bound states, feature a number of interesting properties. Mode dispersion is gate tunable, exhibiting a wide variety of different regimes, including nondispersing flat bands and linear crossings within the bulk bandgap. The ballistic wavelike character of these states resembles the properties of topologically protected states; however, it requires neither topological restrictions nor additional crystal symmetries. The Dirac surface states are weakly sensitive to surface disorder and can dominate edge transport at the energies near the Dirac point.}, } @article {pmid29789338, year = {2018}, author = {Smuga-Otto, K}, title = {Inner Workings: Zebrafish assay forges new approach to drug discovery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5306-5308}, pmid = {29789338}, issn = {1091-6490}, mesh = {Animals ; Biological Assay/*methods ; Drug Discovery/*methods ; *Drug Evaluation, Preclinical ; *Models, Animal ; Toxicity Tests/*methods ; Zebrafish/*physiology ; }, } @article {pmid29789337, year = {2018}, author = {Beans, C}, title = {Science and Culture: Artistic endeavors strive to save coral reefs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5303-5305}, doi = {10.1073/pnas.1807178115}, pmid = {29789337}, issn = {1091-6490}, mesh = {Animals ; *Anthozoa ; *Conservation of Natural Resources ; *Ecosystem ; *Environmental Monitoring ; *Science ; }, } @article {pmid29789226, year = {2018}, author = {Villanueva, L}, title = {Engineering E. coli to Have a Hybrid Archaeal/Bacterial Membrane.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {559-560}, doi = {10.1016/j.tim.2018.05.003}, pmid = {29789226}, issn = {1878-4380}, abstract = {Bacteria and Archaea have membrane lipids with an opposite stereochemistry. The most plausible explanation for this differentiation implies an unstable heterochiral membrane stage. A recent study engineered Escherichia coli with a significant abundance of archaeal lipids showing higher robustness, disproving heterochirality as the driving force for this differentiation.}, } @article {pmid29789015, year = {2018}, author = {Panebianco, C and Andriulli, A and Pazienza, V}, title = {Pharmacomicrobiomics: exploiting the drug-microbiota interactions in anticancer therapies.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {92}, pmid = {29789015}, issn = {2049-2618}, support = {RC1703GA31//Ministero della Salute/International ; RC1503GA40//Ministero della Salute/International ; }, mesh = {Antineoplastic Agents/*metabolism/*therapeutic use ; Bacteria/*metabolism ; Dysbiosis/*chemically induced ; Gastrointestinal Microbiome/*physiology ; Humans ; Intestines/microbiology ; Neoplasms/*drug therapy/microbiology ; Prebiotics ; Probiotics/*therapeutic use ; Synbiotics ; }, abstract = {Cancer is a major health burden worldwide, and despite continuous advances in medical therapies, resistance to standard drugs and adverse effects still represent an important cause of therapeutic failure. There is a growing evidence that gut bacteria can affect the response to chemo- and immunotherapeutic drugs by modulating either efficacy or toxicity. Moreover, intratumor bacteria have been shown to modulate chemotherapy response. At the same time, anticancer treatments themselves significantly affect the microbiota composition, thus disrupting homeostasis and exacerbating discomfort to the patient. Here, we review the existing knowledge concerning the role of the microbiota in mediating chemo- and immunotherapy efficacy and toxicity and the ability of these therapeutic options to trigger dysbiotic condition contributing to the severity of side effects. In addition, we discuss the use of probiotics, prebiotics, synbiotics, postbiotics, and antibiotics as emerging strategies for manipulating the microbiota in order to improve therapeutic outcome or at least ensure patients a better quality of life all along of anticancer treatments.}, } @article {pmid29789010, year = {2018}, author = {Gebru, T and Lentiro, K and Jemal, A}, title = {Perceived behavioural predictors of late initiation to HIV/AIDS care in Gurage zone public health facilities: a cohort study using health belief model.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {336}, pmid = {29789010}, issn = {1756-0500}, mesh = {Acquired Immunodeficiency Syndrome/drug therapy/ethnology ; Adult ; Antiretroviral Therapy, Highly Active/*statistics & numerical data ; Cohort Studies ; Ethiopia/ethnology ; Female ; HIV Infections/drug therapy/*ethnology ; Health Facilities/statistics & numerical data ; Health Knowledge, Attitudes, Practice/*ethnology ; Humans ; Male ; Patient Acceptance of Health Care/*ethnology ; Young Adult ; }, abstract = {OBJECTIVE: The study was aimed to measure incidence density rate and identify perceived behavioural believes of late initiation to HIV/AIDS care in Gurage zone public health facilities from September 2015 to November 2016.

RESULTS: The incidence density rates of late initiation to HIV/AIDS care were 2.21 per 100 person-months of observation. HIV positive individuals who did not perceived susceptibility were 8.46 times more likely delay to start HIV/AIDS care than their counter parts [OR = 8.46 (95% CI 3.92, 18.26)]. HIV infected individuals who did not perceived severity of delayed ART initiation were 6.13 time more likely to delay than HIV infected individuals who perceived its severity [OR = 6.13 (95% CI 2.95, 12.73)]. HIV positive individuals who didn't have self-efficacy were 2.35 times more likely delay to start HIV/AIDS care than HIV positive individuals who have self-efficacy [OR = 2.35 (95% CI 1.09, 5.05)].

CONCLUSIONS: The study revealed that high incidence density rates of delayed initiation for HIV care and variations were explained by poor wealth, and perceived threat and benefit. Therefore, interventions should be designed to initiate care at their diagnosis time.}, } @article {pmid29789000, year = {2018}, author = {Uthayakumar, A and Harrington, D}, title = {Spontaneous splenic rupture complicating primary varicella zoster infection: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {334}, pmid = {29789000}, issn = {1756-0500}, mesh = {Adult ; Humans ; Male ; Splenic Rupture/blood/*diagnosis/diagnostic imaging/*etiology ; Varicella Zoster Virus Infection/*complications/*diagnosis/virology ; }, abstract = {BACKGROUND: Primary varicella zoster virus (VZV) infection is a common illness, predominantly affecting children. Its course is typically benign, although severe complications have been described. Splenic rupture is an extremely rare and potentially fatal complication of primary VZV infection, with only a handful of cases reported in the literature.

CASE PRESENTATION: A 32-year-old Romanian man with no significant past medical history, presented with a 2 day history of sudden onset, worsening generalised abdominal pain and a 1 day history of vomiting. The following day he developed fevers and a generalised widespread erythematous rash consisting of clusters of macules, papules and vesicles at different stages of development. There was no history of sore throat, coryza, arthralgia, myalgia, cough, shortness of breath, weight loss, or night sweats. There was no recent illness and no history of trauma. CT abdomen showed splenic rupture with intra-abdominal haemorrhage. Admission bloods showed anaemia and thrombocytopenia, with haemoglobin 110 g/l and platelets 78 × 109/l. Viral PCR of vesicle fluid from the rash was positive for VZV DNA confirming the clinical diagnosis of primary varicella zoster infection. Viral serology also confirmed recent infection. He was haemodynamically resuscitated, and underwent laparotomy and splenectomy. He was commenced on IV acyclovir and completed a 5 day course. Prior to discharge he was commenced on recommended splenectomy secondary prevention treatment.

CONCLUSION: There are several reported complications of varicella infection, more commonly in the immunocompromised population. Spontaneous splenic rupture is an unusual complication of primary VZV infection. Here we report the sixth known case in the literature. Splenic rupture should be considered in cases of primary varicella in young adults presenting with abdominal pain.}, } @article {pmid29788988, year = {2018}, author = {Engda, T and Moges, F and Gelaw, A and Eshete, S and Mekonnen, F}, title = {Prevalence and antimicrobial susceptibility patterns of extended spectrum beta-lactamase producing Entrobacteriaceae in the University of Gondar Referral Hospital environments, northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {335}, pmid = {29788988}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*pharmacology ; *Drug Resistance, Bacterial ; Enterobacteriaceae/*isolation & purification ; Escherichia coli/*isolation & purification ; Ethiopia ; *Hospitals ; Humans ; Klebsiella pneumoniae/*isolation & purification ; Microbial Sensitivity Tests ; Prevalence ; Proteus mirabilis/*isolation & purification ; beta-Lactamases/*metabolism ; }, abstract = {OBJECTIVE: This study aimed at assessing the magnitude, distribution, and the antimicrobial susceptibility of the extended spectrum beta-lactamase producing Entrobacteriaceae in the University of Gondar Referral Hospital environments.

RESULTS: Out of a total of 384 samples, 14.8% were ESBL producing Entrobacteriaceae, where 42.10% Klebsiella pneumoniae, 35.09% Escherchia coli and 7.01% Proteus mirabilis were the predominant isolates. Most ESBL producing isolates, that is, 24.56, 22.8, and 22.8% were found from waste water, sinks and bedside tables respectively. All ESBL producing Entrobacteriaceae were found to be resistant to ceftriaxone, ceftazidime, cefpirome, cefpodoxime, and amoxicillin with Clavulanic acid. Resistance rate was also high for non-beta-lactam antimicrobials, like chloramphenicol (70.18%), cotrimoxazole (64.91%), norfloxacin (42.10%), ciprofloxacin (43.86%), and gentamicin (19.30%).}, } @article {pmid29788930, year = {2018}, author = {Wei, ZG and Zhang, SW}, title = {NPBSS: a new PacBio sequencing simulator for generating the continuous long reads with an empirical model.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {177}, pmid = {29788930}, issn = {1471-2105}, abstract = {BACKGROUND: PacBio sequencing platform offers longer read lengths than the second-generation sequencing technologies. It has revolutionized de novo genome assembly and enabled the automated reconstruction of reference-quality genomes. Due to its extremely wide range of application areas, fast sequencing simulation systems with high fidelity are in great demand to facilitate the development and comparison of subsequent analysis tools. Although there are several available simulators (e.g., PBSIM, SimLoRD and FASTQSim) that target the specific generation of PacBio libraries, the error rate of simulated sequences is not well matched to the quality value of raw PacBio datasets, especially for PacBio's continuous long reads (CLR).

RESULTS: By analyzing the characteristic features of CLR data from PacBio SMRT (single molecule real time) sequencing, we developed a new PacBio sequencing simulator (called NPBSS) for producing CLR reads. NPBSS simulator firstly samples the read sequences according to the read length logarithmic normal distribution, and choses different base quality values with different proportions. Then, NPBSS computes the overall error probability of each base in the read sequence with an empirical model, and calculates the deletion, substitution and insertion probabilities with the overall error probability to generate the PacBio CLR reads. Alignment results demonstrate that NPBSS fits the error rate of the PacBio CLR reads better than PBSIM and FASTQSim. In addition, the assembly results also show that simulated sequences of NPBSS are more like real PacBio CLR data.

CONCLUSION: NPBSS simulator is convenient to use with efficient computation and flexible parameters setting. Its generating PacBio CLR reads are more like real PacBio datasets.}, } @article {pmid29788925, year = {2018}, author = {Hu, XD and Pan, BZ and Fu, Q and Niu, L and Chen, MS and Xu, ZF}, title = {De novo transcriptome assembly of the eight major organs of Sacha Inchi (Plukenetia volubilis) and the identification of genes involved in α-linolenic acid metabolism.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {380}, pmid = {29788925}, issn = {1471-2164}, support = {2014FB186//Natural Science Foundation of Yunnan Province/ ; 2016FB051//Natural Science Foundation of Yunnan Province/ ; 2017XTBG-T02//CAS 135 program/ ; }, mesh = {Euphorbiaceae/*genetics/*metabolism ; *Gene Expression Profiling ; Genes, Plant/*genetics ; Microsatellite Repeats/genetics ; Molecular Sequence Annotation ; alpha-Linolenic Acid/*metabolism ; }, abstract = {BACKGROUND: Sacha Inchi (Plukenetia volubilis L.), which belongs to the Euphorbiaceae, has been considered a new potential oil crop because of its high content of polyunsaturated fatty acids in its seed oil. The seed oil especially contains high amounts of α-linolenic acid (ALA), which is useful for the prevention of various diseases. However, little is known about the genetic information and genome sequence of Sacha Inchi, which has largely hindered functional genomics and molecular breeding studies.

RESULTS: In this study, a de novo transcriptome assembly based on transcripts sequenced in eight major organs, including roots, stems, shoot apexes, mature leaves, male flowers, female flowers, fruits, and seeds of Sacha Inchi was performed, resulting in a set of 124,750 non-redundant putative transcripts having an average length of 851 bp and an N50 value of 1909 bp. Organ-specific unigenes analysis revealed that the most organ-specific transcripts are found in female flowers (2244 unigenes), whereas a relatively small amount of unigenes are detected to be expressed specifically in other organs with the least in stems (24 unigenes). A total of 42,987 simple sequence repeats (SSRs) were detected, which will contribute to the marker assisted selection breeding of Sacha Inchi. We analyzed expression of genes related to the α-linolenic acid metabolism based on the de novo assembly and annotation transcriptome in Sacha Inchi. It appears that Sacha Inchi accumulates high level of ALA in seeds by strong expression of biosynthesis-related genes and weak expression of degradation-related genes. In particular, the up-regulation of FAD3 and FAD7 is consistent with high level of ALA in seeds of Sacha Inchi compared with in other organs. Meanwhile, several transcription factors (ABI3, LEC1 and FUS3) may regulate key genes involved in oil accumulation in seeds of Sacha Inchi.

CONCLUSIONS: The transcriptome of major organs of Sacha Inchi has been sequenced and de novo assembled, which will expand the genetic information for functional genomic studies of Sacha Inchi. In addition, the identification of candidate genes involved in ALA metabolism will provide useful resources for the genetic improvement of Sacha Inchi and the metabolic engineering of ALA biosynthesis in other plants.}, } @article {pmid29788921, year = {2018}, author = {Frantzeskakis, L and Kracher, B and Kusch, S and Yoshikawa-Maekawa, M and Bauer, S and Pedersen, C and Spanu, PD and Maekawa, T and Schulze-Lefert, P and Panstruga, R}, title = {Signatures of host specialization and a recent transposable element burst in the dynamic one-speed genome of the fungal barley powdery mildew pathogen.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {381}, pmid = {29788921}, issn = {1471-2164}, support = {SPP1819 (PA 861/14-1)//Deutsche Forschungsgemeinschaft/ ; SFB670/3 (grant #13123509)//Deutsche Forschungsgemeinschaft/ ; 10-093504//Strategiske Forskningsråd (DK)/ ; }, mesh = {Ascomycota/*genetics/*physiology ; DNA Copy Number Variations ; DNA Transposable Elements/*genetics ; Gene Duplication ; Gene Expression Profiling ; Genome, Fungal/*genetics ; Hordeum/*microbiology ; Host Specificity/*genetics ; Phylogeny ; Plant Diseases/*microbiology ; }, abstract = {BACKGROUND: Powdery mildews are biotrophic pathogenic fungi infecting a number of economically important plants. The grass powdery mildew, Blumeria graminis, has become a model organism to study host specialization of obligate biotrophic fungal pathogens. We resolved the large-scale genomic architecture of B. graminis forma specialis hordei (Bgh) to explore the potential influence of its genome organization on the co-evolutionary process with its host plant, barley (Hordeum vulgare).

RESULTS: The near-chromosome level assemblies of the Bgh reference isolate DH14 and one of the most diversified isolates, RACE1, enabled a comparative analysis of these haploid genomes, which are highly enriched with transposable elements (TEs). We found largely retained genome synteny and gene repertoires, yet detected copy number variation (CNV) of secretion signal peptide-containing protein-coding genes (SPs) and locally disrupted synteny blocks. Genes coding for sequence-related SPs are often locally clustered, but neither the SPs nor the TEs reside preferentially in genomic regions with unique features. Extended comparative analysis with different host-specific B. graminis formae speciales revealed the existence of a core suite of SPs, but also isolate-specific SP sets as well as congruence of SP CNV and phylogenetic relationship. We further detected evidence for a recent, lineage-specific expansion of TEs in the Bgh genome.

CONCLUSIONS: The characteristics of the Bgh genome (largely retained synteny, CNV of SP genes, recently proliferated TEs and a lack of significant compartmentalization) are consistent with a "one-speed" genome that differs in its architecture and (co-)evolutionary pattern from the "two-speed" genomes reported for several other filamentous phytopathogens.}, } @article {pmid29788916, year = {2018}, author = {Othoum, G and Bougouffa, S and Razali, R and Bokhari, A and Alamoudi, S and Antunes, A and Gao, X and Hoehndorf, R and Arold, ST and Gojobori, T and Hirt, H and Mijakovic, I and Bajic, VB and Lafi, FF and Essack, M}, title = {In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {382}, pmid = {29788916}, issn = {1471-2164}, support = {BAS/1/1624-01-01//King Abdullah University of Science and Technology/ ; BAS/1/1659-01-01//King Abdullah University of Science and Technology/ ; URF/1/1976-06-01//King Abdullah University of Science and Technology/ ; BAS/1/1059-01-01//King Abdullah University of Science and Technology/ ; FCC/1/1976-02-01//King Abdullah University of Science and Technology/ ; FCS/1/2911-01-01//King Abdullah University of Science and Technology/ ; BAS/1/1606-01-01//King Abdullah University of Science and Technology/ ; }, mesh = {Bacillus/enzymology/*genetics/*metabolism ; Bacteriocins/metabolism ; Biological Products/*metabolism ; *Computer Simulation ; Genome, Bacterial/genetics ; *Genomics ; Multigene Family/*genetics ; Peptide Synthases/genetics ; Polyketide Synthases/genetics ; Ribosomes/metabolism ; }, abstract = {BACKGROUND: The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions.

RESULTS: We report the complete circular and annotated genomes of two Red Sea strains, B. paralicheniformis Bac48 isolated from mangrove mud and B. paralicheniformis Bac84 isolated from microbial mat collected from Rabigh Harbor Lagoon in Saudi Arabia. Comparing the genomes of B. paralicheniformis Bac48 and B. paralicheniformis Bac84 with nine publicly available complete genomes of B. licheniformis and three genomes of B. paralicheniformis, revealed that all of the B. paralicheniformis strains in this study are more enriched in nonribosomal peptides (NRPs). We further report the first computationally identified trans-acyltransferase (trans-AT) nonribosomal peptide synthetase/polyketide synthase (PKS/ NRPS) cluster in strains of this species.

CONCLUSIONS: B. paralicheniformis species have more genes associated with biosynthesis of antimicrobial bioactive compounds than other previously characterized species of B. licheniformis, which suggests that these species are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked to adaptations that strains surviving in the Red Sea underwent to survive in the relatively hot and saline ecosystems.}, } @article {pmid29788911, year = {2018}, author = {Wang, Z and Xie, L and Prather, CM and Guo, H and Han, G and Ma, C}, title = {What drives the shift between sexual and clonal reproduction of Caragana stenophylla along a climatic aridity gradient?.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {91}, pmid = {29788911}, issn = {1471-2229}, support = {31570453//National Natural Science Foundation of China/ ; 31170381//National Natural Science Foundation of China/ ; 31760143//National Natural Science Foundation of China/ ; }, mesh = {Caragana/genetics/*physiology ; China ; Clonal Evolution ; Desert Climate ; Droughts ; Reproduction ; }, abstract = {BACKGROUND: The reasons that clonal plants shift between sexual and clonal reproduction have persisted as a knowledge gap in ecological literature. We hypothesized that clonal plants' shifts between sexual and clonal reproduction in different environments are driven by the relative costs of sexual and clonal reproduction. Moreover, we hypothesized plants prioritize sexual reproduction over clonal reproduction. To test these hypotheses, we determined the costs of sexual and clonal reproduction, and proportions of sexual and clonal reproduction of Caragana stenophylla along a climatic aridity gradient (semi-arid, arid, very arid and intensively arid zones) in the Inner Mongolia Steppe using several complementary field experiments.

RESULTS: The cost of sexual reproduction increased while the cost of clonal reproduction decreased as climatic drought stress increased from the semi-arid to the intensively arid zones. The changes in the costs of these reproductive modes drove a shift in the reproductive mode of C. stenophylla from more sexual reproduction in the semi-arid zone to more clonal propagation in the intensively arid zone. However, because of the evolutionary advantages of sexual reproduction, sexual reproduction still held priority over clonal production in C. stenophylla, with the priority of sexual reproduction gradually increasing from the semi-arid to the intensively arid zones.

CONCLUSIONS: Our study suggested that sexual reproduction has relatively high priority in propagation of C. stenophylla. However, if the costs of sexual reproduction are too high, C. stenophylla likely chooses clonal reproduction, and the ratio between sexual and clonal reproduction could be mediated by reproductive cost. These reproductive strategies reflect optimal resource utilization, and allow the persistence of both reproductive modes across stressful conditions depending on their evolutionary advantages.}, } @article {pmid29788909, year = {2018}, author = {Lacey, JA and Allnutt, TR and Vezina, B and Van, TTH and Stent, T and Han, X and Rood, JI and Wade, B and Keyburn, AL and Seemann, T and Chen, H and Haring, V and Johanesen, PA and Lyras, D and Moore, RJ}, title = {Whole genome analysis reveals the diversity and evolutionary relationships between necrotic enteritis-causing strains of Clostridium perfringens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {379}, pmid = {29788909}, issn = {1471-2164}, support = {1.1.2//Poultry Cooperative Research Centre/ ; }, mesh = {Animals ; Chickens/microbiology ; Chromosomes/genetics ; Clostridium perfringens/*genetics/*physiology ; Enteritis/complications/*microbiology ; *Evolution, Molecular ; *Genetic Variation ; Necrosis/complications ; Plasmids/genetics ; }, abstract = {BACKGROUND: Clostridium perfringens causes a range of diseases in animals and humans including necrotic enteritis in chickens and food poisoning and gas gangrene in humans. Necrotic enteritis is of concern in commercial chicken production due to the cost of the implementation of infection control measures and to productivity losses. This study has focused on the genomic analysis of a range of chicken-derived C. perfringens isolates, from around the world and from different years. The genomes were sequenced and compared with 20 genomes available from public databases, which were from a diverse collection of isolates from chickens, other animals, and humans. We used a distance based phylogeny that was constructed based on gene content rather than sequence identity. Similarity between strains was defined as the number of genes that they have in common divided by their total number of genes. In this type of phylogenetic analysis, evolutionary distance can be interpreted in terms of evolutionary events such as acquisition and loss of genes, whereas the underlying properties (the gene content) can be interpreted in terms of function. We also compared these methods to the sequence-based phylogeny of the core genome.

RESULTS: Distinct pathogenic clades of necrotic enteritis-causing C. perfringens were identified. They were characterised by variable regions encoded on the chromosome, with predicted roles in capsule production, adhesion, inhibition of related strains, phage integration, and metabolism. Some strains have almost identical genomes, even though they were isolated from different geographic regions at various times, while other highly distant genomes appear to result in similar outcomes with regard to virulence and pathogenesis.

CONCLUSIONS: The high level of diversity in chicken isolates suggests there is no reliable factor that defines a chicken strain of C. perfringens, however, disease-causing strains can be defined by the presence of netB-encoding plasmids. This study reveals that horizontal gene transfer appears to play a significant role in genetic variation of the C. perfringens chromosome as well as the plasmid content within strains.}, } @article {pmid29788904, year = {2018}, author = {Takeshima, SN and Corbi-Botto, C and Giovambattista, G and Aida, Y}, title = {Genetic diversity of BoLA-DRB3 in South American Zebu cattle populations.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {33}, pmid = {29788904}, issn = {1471-2156}, support = {18255013//Japan Society for the Promotion of Science/ ; 16H02590//Japan Society for the Promotion of Science/ ; 16K08039//Japan Society for the Promotion of Science/ ; 25450405//Japan Society for the Promotion of Science/ ; }, abstract = {BACKGROUND: Bovine leukocyte antigens (BoLAs) are used extensively as markers of disease and immunological traits in cattle. However, until now, characterization of BoLA gene polymorphisms in Zebu breeds using high resolution typing methods has been poor. Here, we used a polymerase chain reaction sequence-based typing (PCR-SBT) method to sequence exon 2 of the BoLA class II DRB3 gene from 421 cattle (116 Bolivian Nellore, 110 Bolivian Gir, and 195 Peruvian Nellore-Brahman). Data from 1416 Taurine and Zebu samples were also included in the analysis.

RESULTS: We identified 46 previously reported alleles and no novel variants. Of note, 1/3 of the alleles were detected only in Zebu cattle. Comparison of the degree of genetic variability at the population and sequence levels with genetic distance in the three above mentioned breeds and nine previously reported breeds revealed that Zebu breeds had a gene diversity score higher than 0.86, a nucleotide diversity score higher than 0.06, and a mean number of pairwise differences greater than 16, being similar to those estimated for other cattle breeds. A neutrality test revealed that only Nellore-Brahman cattle showed the even gene frequency distribution expected under a balanced selection scenario. The FST index and the exact G test showed significant differences across all cattle populations (FST = 0.057; p < 0.001). Neighbor-joining trees and principal component analysis identified two major clusters: one comprising mainly European Taurine breeds and a second comprising Zebu breeds. This is consistent with the historical and geographical origin of these breeds. Some of these differences may be explained by variation of amino acid motifs at antigen-binding sites.

CONCLUSIONS: The results presented herein show that the historical divergence between Taurine and Zebu cattle breeds is a result of origin, selection, and adaptation events, which would explain the observed differences in BoLA-DRB3 gene diversity between the two major bovine types. This allelic information will be important for investigating the relationship between the major histocompatibility complex and disease, and contribute to an ongoing effort to catalog bovine MHC allele frequencies according to breed and location.}, } @article {pmid29788493, year = {2018}, author = {Byrne, L and Chapleau, F and Aris-Brosou, S}, title = {How the Central American Seaway and an Ancient Northern Passage Affected Flatfish Diversification.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1982-1989}, doi = {10.1093/molbev/msy104}, pmid = {29788493}, issn = {1537-1719}, abstract = {While the natural history of flatfish has been debated for decades, the mode of diversification of this biologically and economically important group has never been elucidated. To address this question, we assembled the largest molecular data set to date, covering > 300 species (out of ca. 800 extant), from 13 of the 14 known families over nine genes, and employed relaxed molecular clocks to uncover their patterns of diversification. As the fossil record of flatfish is contentious, we used sister species distributed on both sides of the American continent to calibrate clock models based on the closure of the Central American Seaway (CAS), and on their current species range. We show that flatfish diversified in two bouts, as species that are today distributed around the equator diverged during the closure of CAS, whereas those with a northern range diverged after this, hereby suggesting the existence of a postCAS closure dispersal for these northern species, most likely along a trans-Arctic northern route, a hypothesis fully compatible with paleogeographic reconstructions.}, } @article {pmid29788479, year = {2018}, author = {Kuang, MC and Kominek, J and Alexander, WG and Cheng, JF and Wrobel, RL and Hittinger, CT}, title = {Repeated Cis-Regulatory Tuning of a Metabolic Bottleneck Gene during Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1968-1981}, pmid = {29788479}, issn = {1537-1719}, abstract = {Repeated evolutionary events imply underlying genetic constraints that can make evolutionary mechanisms predictable. Morphological traits are thought to evolve frequently through cis-regulatory changes because these mechanisms bypass constraints in pleiotropic genes that are reused during development. In contrast, the constraints acting on metabolic traits during evolution are less well studied. Here we show how a metabolic bottleneck gene has repeatedly adopted similar cis-regulatory solutions during evolution, likely due to its pleiotropic role integrating flux from multiple metabolic pathways. Specifically, the genes encoding phosphoglucomutase activity (PGM1/PGM2), which connect GALactose catabolism to glycolysis, have gained and lost direct regulation by the transcription factor Gal4 several times during yeast evolution. Through targeted mutations of predicted Gal4-binding sites in yeast genomes, we show this galactose-mediated regulation of PGM1/2 supports vigorous growth on galactose in multiple yeast species, including Saccharomyces uvarum and Lachancea kluyveri. Furthermore, the addition of galactose-inducible PGM1 alone is sufficient to improve the growth on galactose of multiple species that lack this regulation, including Saccharomyces cerevisiae. The strong association between regulation of PGM1/2 by Gal4 even enables remarkably accurate predictions of galactose growth phenotypes between closely related species. This repeated mode of evolution suggests that this specific cis-regulatory connection is a common way that diverse yeasts can govern flux through the pathway, likely due to the constraints imposed by this pleiotropic bottleneck gene. Since metabolic pathways are highly interconnected, we argue that cis-regulatory evolution might be widespread at pleiotropic genes that control metabolic bottlenecks and intersections.}, } @article {pmid29788432, year = {2018}, author = {Cai, JN and Jung, JE and Lee, MH and Choi, HM and Jeon, JG}, title = {Sucrose challenges to Streptococcus mutans biofilms and the curve fitting for the biofilm changes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy091}, pmid = {29788432}, issn = {1574-6941}, abstract = {The relationship between sugar level and development of dental caries has long been a main topic in dentistry. However, as a ubiquitous component of the modern diet, sucrose is mainly derived from three meals a day, rather than a long time exposure. In this study, various concentrations of sucrose were provided to Streptococcus mutans biofilms for 1 h per exposure (three times per day) to imitate a human meal pattern. And then the relationship between sucrose concentration and changes in the treated biofilms was determined. The results indicated that the components and acid production of the treated biofilms changed in a second-order polynomial curve pattern with sucrose concentration increase, which were confirmed by CLSM and SEM analyses. However, gene expression related to extracellular polysaccharides (EPS) formation, acid production and tolerance was up-regulated with sucrose concentration increase, which might have been due to compensation for the decrease in EPS formation and acid production by the biofilms at higher concentrations of sucrose. These findings suggest that sucrose in the range of 1%-5% can support the highest acid production and accumulation of S. mutans biofilms, which may further increase its cariogenic potential. However, additional studies are required to confirm the relationships in human cariogenic biofilms.}, } @article {pmid29788330, year = {2018}, author = {Stern, DB and Crandall, KA}, title = {The Evolution of Gene Expression Underlying Vision Loss in Cave Animals.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2005-2014}, pmid = {29788330}, issn = {1537-1719}, abstract = {Dissecting the evolutionary genetic processes underlying eye reduction and vision loss in obligate cave-dwelling organisms has been a long-standing challenge in evolutionary biology. Independent vision loss events in related subterranean organisms can provide critical insight into these processes as well as into the nature of convergent loss of complex traits. Advances in evolutionary developmental biology have illuminated the significant role of heritable gene expression variation in the evolution of new forms. Here, we analyze gene expression variation in adult eye tissue across the freshwater crayfish, representing four independent vision-loss events in caves. Species and individual expression patterns cluster by eye function rather than phylogeny, suggesting convergence in transcriptome evolution in independently blind animals. However, this clustering is not greater than what is observed in surface species with conserved eye function after accounting for phylogenetic expectations. Modeling expression evolution suggests that there is a common increase in evolutionary rates in the blind lineages, consistent with a relaxation of selective constraint maintaining optimal expression levels. This is evidence for a repeated loss of expression constraint in the transcriptomes of blind animals and that convergence occurs via a similar trajectory through genetic drift.}, } @article {pmid29788292, year = {2018}, author = {Muntané, G and Farré, X and Rodríguez, JA and Pegueroles, C and Hughes, DA and de Magalhães, JP and Gabaldón, T and Navarro, A}, title = {Biological Processes Modulating Longevity across Primates: A Phylogenetic Genome-Phenome Analysis.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1990-2004}, pmid = {29788292}, issn = {1537-1719}, abstract = {Aging is a complex process affecting different species and individuals in different ways. Comparing genetic variation across species with their aging phenotypes will help understanding the molecular basis of aging and longevity. Although most studies on aging have so far focused on short-lived model organisms, recent comparisons of genomic, transcriptomic, and metabolomic data across lineages with different lifespans are unveiling molecular signatures associated with longevity. Here, we examine the relationship between genomic variation and maximum lifespan across primate species. We used two different approaches. First, we searched for parallel amino-acid mutations that co-occur with increases in longevity across the primate linage. Twenty-five such amino-acid variants were identified, several of which have been previously reported by studies with different experimental setups and in different model organisms. The genes harboring these mutations are mainly enriched in functional categories such as wound healing, blood coagulation, and cardiovascular disorders. We demonstrate that these pathways are highly enriched for pleiotropic effects, as predicted by the antagonistic pleiotropy theory of aging. A second approach was focused on changes in rates of protein evolution across the primate phylogeny. Using the phylogenetic generalized least squares, we show that some genes exhibit strong correlations between their evolutionary rates and longevity-associated traits. These include genes in the Sphingosine 1-phosphate pathway, PI3K signaling, and the Thrombin/protease-activated receptor pathway, among other cardiovascular processes. Together, these results shed light into human senescence patterns and underscore the power of comparative genomics to identify pathways related to aging and longevity.}, } @article {pmid29788279, year = {2018}, author = {Tarver, JE and Taylor, RS and Puttick, MN and Lloyd, GT and Pett, W and Fromm, B and Schirrmeister, BE and Pisani, D and Peterson, KJ and Donoghue, PCJ}, title = {Well-Annotated microRNAomes Do Not Evidence Pervasive miRNA Loss.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1457-1470}, pmid = {29788279}, issn = {1759-6653}, mesh = {Animals ; Conserved Sequence/genetics ; Evolution, Molecular ; MicroRNAs/*genetics ; Molecular Sequence Annotation/methods ; Phenotype ; Phylogeny ; }, abstract = {microRNAs are conserved noncoding regulatory factors implicated in diverse physiological and developmental processes in multicellular organisms, as causal macroevolutionary agents and for phylogeny inference. However, the conservation and phylogenetic utility of microRNAs has been questioned on evidence of pervasive loss. Here, we show that apparent widespread losses are, largely, an artefact of poorly sampled and annotated microRNAomes. Using a curated data set of animal microRNAomes, we reject the view that miRNA families are never lost, but they are rarely lost (92% are never lost). A small number of families account for a majority of losses (1.7% of families account for >45% losses), and losses are associated with lineages exhibiting phenotypic simplification. Phylogenetic analyses based on the presence/absence of microRNA families among animal lineages, and based on microRNA sequences among Osteichthyes, demonstrate the power of these small data sets in phylogenetic inference. Perceptions of widespread evolutionary loss of microRNA families are due to the uncritical use of public archives corrupted by spurious microRNA annotations, and failure to discriminate false absences that occur because of incomplete microRNAome annotation.}, } @article {pmid29788252, year = {2018}, author = {Bernier, CR and Petrov, AS and Kovacs, NA and Penev, PI and Williams, LD}, title = {Translation: The Universal Structural Core of Life.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {2065-2076}, pmid = {29788252}, issn = {1537-1719}, abstract = {The Universal Gene Set of Life (UGSL) is common to genomes of all extant organisms. The UGSL is small, consisting of <100 genes, and is dominated by genes encoding the translation system. Here we extend the search for biological universality to three dimensions. We characterize and quantitate the universality of structure of macromolecules that are common to all of life. We determine that around 90% of prokaryotic ribosomal RNA (rRNA) forms a common core, which is the structural and functional foundation of rRNAs of all cytoplasmic ribosomes. We have established a database, which we call the Sparse and Efficient Representation of the Extant Biology (the SEREB database). This database contains complete and cross-validated rRNA sequences of species chosen, as far as possible, to sparsely and efficiently sample all known phyla. Atomic-resolution structures of ribosomes provide data for structural comparison and validation of sequence-based models. We developed a similarity statistic called pairing adjusted sequence entropy, which characterizes paired nucleotides by their adherence to covariation and unpaired nucleotides by conventional conservation of identity. For canonically paired nucleotides the unit of structure is the nucleotide pair. For unpaired nucleotides, the unit of structure is the nucleotide. By quantitatively defining the common core of rRNA, we systematize the conservation and divergence of the translational system across the tree of life, and can begin to understand the unique evolutionary pressures that cause its universality. We explore the relationship between ribosomal size and diversity, geological time, and organismal complexity.}, } @article {pmid29788251, year = {2018}, author = {}, title = {Corrigendum.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1247}, doi = {10.1093/gbe/evy090}, pmid = {29788251}, issn = {1759-6653}, } @article {pmid29788250, year = {2018}, author = {Vizueta, J and Rozas, J and Sánchez-Gracia, A}, title = {Comparative Genomics Reveals Thousands of Novel Chemosensory Genes and Massive Changes in Chemoreceptor Repertories across Chelicerates.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1221-1236}, pmid = {29788250}, issn = {1759-6653}, mesh = {Animals ; Arthropod Proteins/*genetics ; Arthropods/classification/*genetics ; *Evolution, Molecular ; *Gene Duplication ; Genome/genetics ; *Genomics ; Multigene Family ; Phylogeny ; }, abstract = {Chemoreception is a widespread biological function that is essential for the survival, reproduction, and social communication of animals. Though the molecular mechanisms underlying chemoreception are relatively well known in insects, they are poorly studied in the other major arthropod lineages. Current availability of a number of chelicerate genomes constitutes a great opportunity to better characterize gene families involved in this important function in a lineage that emerged and colonized land independently of insects. At the same time, that offers new opportunities and challenges for the study of this interesting animal branch in many translational research areas. Here, we have performed a comprehensive comparative genomics study that explicitly considers the high fragmentation of available draft genomes and that for the first time included complete genome data that cover most of the chelicerate diversity. Our exhaustive searches exposed thousands of previously uncharacterized chemosensory sequences, most of them encoding members of the gustatory and ionotropic receptor families. The phylogenetic and gene turnover analyses of these sequences indicated that the whole-genome duplication events proposed for this subphylum would not explain the differences in the number of chemoreceptors observed across species. A constant and prolonged gene birth and death process, altered by episodic bursts of gene duplication yielding lineage-specific expansions, has contributed significantly to the extant chemosensory diversity in this group of animals. This study also provides valuable insights into the origin and functional diversification of other relevant chemosensory gene families different from receptors, such as odorant-binding proteins and other related molecules.}, } @article {pmid29788231, year = {2018}, author = {Barriuso, J and Hogan, DA and Keshavarz, T and Martínez, MJ}, title = {Role of quorum sensing and chemical communication in fungal biotechnology and pathogenesis.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {627-638}, pmid = {29788231}, issn = {1574-6976}, support = {R01 AI127548/AI/NIAID NIH HHS/United States ; }, mesh = {*Biotechnology ; Fungi/genetics/pathogenicity/*physiology ; Quorum Sensing/*physiology ; }, abstract = {Microbial cells do not live in isolation in their environment, but rather they communicate with each other using chemical signals. This sophisticated mode of cell-to-cell signalling, known as quorum sensing, was first discovered in bacteria, and coordinates the behaviour of microbial population behaviour in a cell-density-dependent manner. More recently, these mechanisms have been described in eukaryotes, particularly in fungi, where they regulate processes such as pathogenesis, morphological differentiation, secondary metabolite production and biofilm formation. In this manuscript, we review the information available to date on these processes in yeast, dimorphic fungi and filamentous fungi. We analyse the diverse chemical 'languages' used by different groups of fungi, their possible cross-talk and interkingdom interactions with other organisms. We discuss the existence of these mechanisms in multicellular organisms, the ecophysiological role of QS in fungal colonisation and the potential applications of these mechanisms in biotechnology and pathogenesis.}, } @article {pmid29788151, year = {2018}, author = {Bressuire-Isoard, C and Broussolle, V and Carlin, F}, title = {Sporulation environment influences spore properties in Bacillus: evidence and insights on underlying molecular and physiological mechanisms.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {614-626}, doi = {10.1093/femsre/fuy021}, pmid = {29788151}, issn = {1574-6976}, mesh = {Bacillus/genetics/*physiology ; Bacterial Proteins/genetics/metabolism ; *Environment ; Spores, Bacterial/*chemistry/metabolism ; }, abstract = {Bacterial spores are resistant to physical and chemical insults, which makes them a major concern for public health and industry. Spores help bacteria to survive extreme environmental conditions that vegetative cells cannot tolerate. Spore resistance and dormancy are important properties for applications in medicine, veterinary health, food safety, crop protection and other domains. The resistance of bacterial spores results from a protective multilayered structure and from the unique composition of the spore core. The mechanisms of sporulation and germination, the first stage after breaking of dormancy, and organization of spore structure have been extensively studied in Bacillus species. This review aims to illustrate how far the structure, composition and properties of spores are shaped by the environmental conditions in which spores form. We look at the physiological and molecular mechanisms underpinning how sporulation media and environment deeply affect spore yield, spore properties like resistance to wet heat and physical and chemical agents, germination and further growth. For example, spore core water content decreases as sporulation temperature increases, and resistance to wet heat increases. Controlling the fate of Bacillus spores is pivotal to controlling bacterial risks and process efficiencies in, for example, the food industry, and better control hinges on better understanding how sporulation conditions influence spore properties.}, } @article {pmid29788113, year = {2018}, author = {Duchêne, DA and Duchêne, S and Ho, SYW}, title = {Differences in Performance among Test Statistics for Assessing Phylogenomic Model Adequacy.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1375-1388}, pmid = {29788113}, issn = {1759-6653}, mesh = {Amino Acid Substitution/genetics ; Computer Simulation ; Evolution, Molecular ; Genomics/methods ; *Models, Genetic ; *Models, Statistical ; *Phylogeny ; Reproducibility of Results ; }, abstract = {Statistical phylogenetic analyses of genomic data depend on models of nucleotide or amino acid substitution. The adequacy of these substitution models can be assessed using a number of test statistics, allowing the model to be rejected when it is found to provide a poor description of the evolutionary process. A potentially valuable use of model-adequacy test statistics is to identify when data sets are likely to produce unreliable phylogenetic estimates, but their differences in performance are rarely explored. We performed a comprehensive simulation study to identify test statistics that are sensitive to some of the most commonly cited sources of phylogenetic estimation error. Our results show that, for many test statistics, traditional thresholds for assessing model adequacy can fail to reject the model when the phylogenetic inferences are inaccurate and imprecise. This is particularly problematic when analysing loci that have few informative sites. We propose new thresholds for assessing substitution model adequacy and demonstrate their effectiveness in analyses of three phylogenomic data sets. These thresholds lead to frequent rejection of the model for loci that yield topological inferences that are imprecise and are likely to be inaccurate. We also propose the use of a summary statistic that provides a practical assessment of overall model adequacy. Our approach offers a promising means of enhancing model choice in genome-scale data sets, potentially leading to improvements in the reliability of phylogenomic inference.}, } @article {pmid29788112, year = {2018}, author = {Suzuki, HC and Ozaki, K and Makino, T and Uchiyama, H and Yajima, S and Kawata, M}, title = {Evolution of Gustatory Receptor Gene Family Provides Insights into Adaptation to Diverse Host Plants in Nymphalid Butterflies.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1351-1362}, pmid = {29788112}, issn = {1759-6653}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Butterflies/*genetics ; Evolution, Molecular ; Female ; Gene Duplication/genetics ; Herbivory/genetics ; Host Specificity/*genetics ; Insect Proteins/*genetics ; Lepidoptera/*genetics ; Oviposition/genetics ; Phylogeny ; }, abstract = {The host plant range of herbivorous insects is a major aspect of insect-plant interaction, but the genetic basis of host range expansion in insects is poorly understood. In butterflies, gustatory receptor genes (GRs) play important roles in host plant selection by ovipositing females. Since several studies have shown associations between the repertoire sizes of chemosensory gene families and the diversity of resource use, we hypothesized that the increase in the number of genes in the GR family is associated with host range expansion in butterflies. Here, we analyzed the evolutionary dynamics of GRs among related species, including the host generalist Vanessa cardui and three specialists. Although the increase of the GR repertoire itself was not observed, we found that the gene birth rate of GRs was the highest in the lineage leading to V. cardui compared with other specialist lineages. We also identified two taxon-specific subfamilies of GRs, characterized by frequent lineage-specific duplications and higher non-synonymous substitution rates. Together, our results suggest that frequent gene duplications in GRs, which might be involved in the detection of plant secondary metabolites, were associated with host range expansion in the V. cardui lineage. These evolutionary patterns imply that the capability to perceive various compounds during host selection was favored during adaptation to diverse host plants.}, } @article {pmid29788056, year = {2018}, author = {Miquel Guennoc, C and Rose, C and Labbé, J and Deveau, A}, title = {Bacterial biofilm formation on the hyphae of ectomycorrhizal fungi: a widespread ability under controls?.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy093}, pmid = {29788056}, issn = {1574-6941}, abstract = {Ectomycorrhizal (ECM) fungi establish symbiosis with roots of most trees of boreal and temperate ecosystems and are major drivers of nutrient fluxes between trees and the soil. ECM fungi constantly interact with bacteria all along their life cycle and the extended networks of hyphae provide a habitat for complex bacterial communities. Despite the important effects these bacteria can have on the growth and activities of ECM fungi, little is known about the mechanisms by which these microorganisms interact. Here we investigated the ability of bacteria to form biofilm on the hyphae of the ECM fungus Laccaria bicolor. We showed that the ability to form biofilms on the hyphae of the ECM fungus is widely shared among soil bacteria. Conversely, some fungi, belonging to the Ascomycete class, did not allow for the formation of bacterial biofilms on their surfaces. The formation of biofilms was also modulated by the presence of tree roots and ectomycorrhizae, suggesting that biofilm formation does not occur randomly in soil but that it is regulated by several biotic factors. In addition, our study demonstrated that the formation of bacterial biofilm on fungal hyphae relies on the production of networks of filaments made of extracellular DNA.}, } @article {pmid29788052, year = {2018}, author = {Boulain, H and Legeai, F and Guy, E and Morlière, S and Douglas, NE and Oh, J and Murugan, M and Smith, M and Jaquiéry, J and Peccoud, J and White, FF and Carolan, JC and Simon, JC and Sugio, A}, title = {Fast Evolution and Lineage-Specific Gene Family Expansions of Aphid Salivary Effectors Driven by Interactions with Host-Plants.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1554-1572}, pmid = {29788052}, issn = {1759-6653}, mesh = {Adaptation, Biological/genetics ; Animals ; Aphids/*genetics ; Evolution, Molecular ; Host-Pathogen Interactions/*genetics ; Insect Proteins/*genetics ; Plants/*parasitology ; Proteomics/methods ; Salivary Proteins and Peptides/*genetics ; Transcriptome/genetics ; Up-Regulation/genetics ; Virulence/genetics ; }, abstract = {Effector proteins play crucial roles in plant-parasite interactions by suppressing plant defenses and hijacking plant physiological responses to facilitate parasite invasion and propagation. Although effector proteins have been characterized in many microbial plant pathogens, their nature and role in adaptation to host plants are largely unknown in insect herbivores. Aphids rely on salivary effector proteins injected into the host plants to promote phloem sap uptake. Therefore, gaining insight into the repertoire and evolution of aphid effectors is key to unveiling the mechanisms responsible for aphid virulence and host plant specialization. With this aim in mind, we assembled catalogues of putative effectors in the legume specialist aphid, Acyrthosiphon pisum, using transcriptomics and proteomics approaches. We identified 3,603 candidate effector genes predicted to be expressed in A. pisum salivary glands (SGs), and 740 of which displayed up-regulated expression in SGs in comparison to the alimentary tract. A search for orthologs in 17 arthropod genomes revealed that SG-up-regulated effector candidates of A. pisum are enriched in aphid-specific genes and tend to evolve faster compared with the whole gene set. We also found that a large fraction of proteins detected in the A. pisum saliva belonged to three gene families, of which certain members show evidence consistent with positive selection. Overall, this comprehensive analysis suggests that the large repertoire of effector candidates in A. pisum constitutes a source of novelties promoting plant adaptation to legumes.}, } @article {pmid29788048, year = {2018}, author = {Göbel, U and Arce, AL and He, F and Rico, A and Schmitz, G and de Meaux, J}, title = {Robustness of Transposable Element Regulation but No Genomic Shock Observed in Interspecific Arabidopsis Hybrids.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1403-1415}, pmid = {29788048}, issn = {1759-6653}, mesh = {Arabidopsis/*genetics ; DNA Transposable Elements/*genetics ; Epigenesis, Genetic/genetics ; Gene Expression Regulation, Plant/*genetics ; Genome, Plant/*genetics ; Genomics/methods ; Histones/genetics ; Hybridization, Genetic ; Transcription, Genetic/genetics ; }, abstract = {The merging of two divergent genomes in a hybrid is believed to trigger a "genomic shock", disrupting gene regulation and transposable element (TE) silencing. Here, we tested this expectation by comparing the pattern of expression of transposable elements in their native and hybrid genomic context. For this, we sequenced the transcriptome of the Arabidopsis thaliana genotype Col-0, the A. lyrata genotype MN47 and their F1 hybrid. Contrary to expectations, we observe that the level of TE expression in the hybrid is strongly correlated to levels in the parental species. We detect that at most 1.1% of expressed transposable elements belonging to two specific subfamilies change their expression level upon hybridization. Most of these changes, however, are of small magnitude. We observe that the few hybrid-specific modifications in TE expression are more likely to occur when TE insertions are close to genes. In addition, changes in epigenetic histone marks H3K9me2 and H3K27me3 following hybridization do not coincide with TEs with changed expression. Finally, we further examined TE expression in parents and hybrids exposed to severe dehydration stress. Despite the major reorganization of gene and TE expression by stress, we observe that hybridization does not lead to increased disorganization of TE expression in the hybrid. Although our study did not examine TE transposition activity in hybrids, the examination of the transcriptome shows that TE expression is globally robust to hybridization. The term "genomic shock" is perhaps not appropriate to describe transcriptional modification in a viable hybrid merging divergent genomes.}, } @article {pmid29787835, year = {2018}, author = {Díaz-Pérez, AL and Núñez, C and Meza Carmen, V and Campos-García, J}, title = {The expression of the genes involved in leucine catabolism of Pseudomonas aeruginosa is controlled by the transcriptional regulator LiuR and by the CbrAB/Crc system.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {324-334}, doi = {10.1016/j.resmic.2018.05.004}, pmid = {29787835}, issn = {1769-7123}, mesh = {Bacterial Proteins/*genetics ; Base Sequence ; Carbon/metabolism ; Gene Expression Regulation, Bacterial/*genetics ; Leucine/*metabolism ; Pseudomonas aeruginosa/genetics/*metabolism ; Repressor Proteins/*genetics/metabolism ; Transcription Factors/*genetics ; Transcription, Genetic/genetics ; }, abstract = {Pseudomonas aeruginosa metabolizes leucine through the leucine/isovalerate utilization pathway, whose enzymes are encoded in the liuRABCDE gene cluster (liu). In this study, we investigated the role of the LiuR protein in the liu cluster regulation. Our results indicated that liu expression is regulated at the transcriptional level by LiuR. Mobility shift assays using purified recombinant His-tagged LiuR showed that it was able to bind at the promoter region of liuR, in a dose-dependent manner. Results revealed that expression of the liu operon is subjected to carbon catabolite repression control (CCR); protein LiuD was strongly expressed in the presence of leucine, but it was repressed in the presence of glucose or succinate. Furthermore, this CCR control was dependent on LiuR as in the liuR- mutant the LiuD protein was strongly expressed in all the carbon sources tested. In agreement with this result, in the absence of the Crc protein, LiuD was expressed independently of the carbon source used, whereas in a cbrB- mutant its expression was severely impaired. The results indicated that the liu cluster is subjected to a coordinated transcriptional and translational regulation by the LiuR repressor and by the CbrAB/Crc system, respectively, in response to the available carbon source.}, } @article {pmid29787834, year = {2018}, author = {Neuberger, A and Du, D and Luisi, BF}, title = {Structure and mechanism of bacterial tripartite efflux pumps.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {401-413}, doi = {10.1016/j.resmic.2018.05.003}, pmid = {29787834}, issn = {1769-7123}, mesh = {Bacterial Proteins/*chemistry/genetics/metabolism ; Gram-Negative Bacteria/chemistry/genetics/*metabolism ; Membrane Transport Proteins/*chemistry/genetics/metabolism ; Models, Molecular ; Protein Conformation ; }, abstract = {Efflux pumps are membrane proteins which contribute to multi-drug resistance. In Gram-negative bacteria, some of these pumps form complex tripartite assemblies in association with an outer membrane channel and a periplasmic membrane fusion protein. These tripartite machineries span both membranes and the periplasmic space, and they extrude from the bacterium chemically diverse toxic substrates. In this chapter, we summarise current understanding of the structural architecture, functionality, and regulation of tripartite multi-drug efflux assemblies.}, } @article {pmid29787799, year = {2018}, author = {Vasconcelos, S and Soares, ML and Sakuragui, CM and Croat, TB and Oliveira, G and Benko-Iseppon, AM}, title = {New insights on the phylogenetic relationships among the traditional Philodendron subgenera and the other groups of the Homalomena clade (Araceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {168-178}, doi = {10.1016/j.ympev.2018.05.017}, pmid = {29787799}, issn = {1095-9513}, abstract = {Philodendron (Araceae) is one of the largest Neotropical plant genera, with approximately 500 species and at least 1000 species predicted. There is a considerable ecological diversity in the group, although most species occur in the humid forests of tropical America. Despite being relatively well-studied in taxonomic analyses, the relationships among the traditional morphological groups of the genus are not well-established, mainly regarding the three traditional subgenera, referred here as Philodendron sensu lato (s.l.), P. subg. Pteromischum, P. subg. Philodendron and P. subg. Meconostigma, which was recently recognized as a separate genus, Thaumatophyllum. Therefore, the present work evaluates the phylogenetic position and the monophyly of Philodendron s.l. and its three main subdivisions, and the sister groups within the Homalomena clade, which also includes the Neotropical genus Adelonema, the two Asian genera Homalomena and Furtadoa, and the two African genera Cercestis and Culcasia, by means of molecular phylogenetic approaches including chloroplast DNA (atpF-atpH, rpl32-trnL, trnQ-5'-rps16 and trnV-ndhC) and nuclear (ITS2) markers. The monophyly of Philodendron s.l. and its three lineages is confirmed and our analyses corroborate previous morphologic data indicating Thaumatophyllum as sister to the clade formed by P. subg. Pteromischum and P. subg. Philodendron.}, } @article {pmid29787744, year = {2018}, author = {Meng, Q and Mongan, M and Wang, J and Xia, Y}, title = {Repression of MAP3K1 expression and JNK activity by canonical Wnt signaling.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {129-136}, pmid = {29787744}, issn = {1095-564X}, support = {R01 EY015227/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Ectoderm/metabolism ; Eyelids/*embryology/enzymology/physiology ; Gene Expression Regulation, Developmental ; Intercellular Signaling Peptides and Proteins/genetics/metabolism ; MAP Kinase Kinase Kinase 1/genetics/*metabolism ; *MAP Kinase Signaling System ; Mice ; Morphogenesis/genetics ; Signal Transduction ; *Wnt Signaling Pathway ; }, abstract = {Morphogenesis is a complex and highly coordinated process orchestrated by temporal spatial activity of developmental pathways. How the different pathways interact to guide the developmental program remains an intriguing and open question. MAP3K1-JNK and Wnt are signaling pathways crucial for embryonic eyelid closure, an epithelial morphogenetic event conserved in mammals. Here we used a mouse model of eyelid development and genetic and biochemistry tools to investigate the relationships between the two pathways. We found that Wnt activation repressed MAP3K1 expression. Using Axin-LacZ reporter mice, spatial Wnt activity was detected in the leading edge of the developing eyelid. Conditional knockout of Wntless (Wls) in ocular surface ectoderm blocked eyelid formation, and significantly increased MAP3K1 expression in eyelid cells at the nasal canthus region. Conversely, knockout of Dkk2, encoding a canonical Wnt antagonist, resulted in an increase of Wnt activity in cells at the upper eyelid margin near the nasal canthus. Up-regulation of Wnt signaling in the Dkk2-knockout embryos corresponded to down-regulation of MAP3K1 expression. In vitro data showed that Wnt3a treatment decreased MAP3K1 promoter activity, whereas activation of Wnt by lithium chloride inhibited MAP3K1 expression, and attenuated MAP3K1-mediated JNK activity. Our data identify a unique signal crosstalk between Wnt signaling and the MAP3K1-JNK pathway in epithelial morphogenesis.}, } @article {pmid29786942, year = {2018}, author = {Ramos, JL and Bonfante, P}, title = {José-Miguel Barea 1942-2018: the man that always smiles.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2319-2321}, doi = {10.1111/1462-2920.14267}, pmid = {29786942}, issn = {1462-2920}, } @article {pmid29786565, year = {2018}, author = {Lyall, MJ and Cartier, J and Thomson, JP and Cameron, K and Meseguer-Ripolles, J and O'Duibhir, E and Szkolnicka, D and Villarin, BL and Wang, Y and Blanco, GR and Dunn, WB and Meehan, RR and Hay, DC and Drake, AJ}, title = {Modelling non-alcoholic fatty liver disease in human hepatocyte-like cells.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786565}, issn = {1471-2970}, support = {//Wellcome Trust/United Kingdom ; MC_PC_U127574433//Medical Research Council/United Kingdom ; MR/K026666/1//Medical Research Council/United Kingdom ; }, abstract = {Non-alcoholic fatty liver disease (NAFLD) is the most common cause of liver disease in developed countries. An in vitro NAFLD model would permit mechanistic studies and enable high-throughput therapeutic screening. While hepatic cancer-derived cell lines are a convenient, renewable resource, their genomic, epigenomic and functional alterations mean their utility in NAFLD modelling is unclear. Additionally, the epigenetic mark 5-hydroxymethylcytosine (5hmC), a cell lineage identifier, is rapidly lost during cell culture, alongside expression of the Ten-eleven-translocation (TET) methylcytosine dioxygenase enzymes, restricting meaningful epigenetic analysis. Hepatocyte-like cells (HLCs) derived from human embryonic stem cells can provide a non-neoplastic, renewable model for liver research. Here, we have developed a model of NAFLD using HLCs exposed to lactate, pyruvate and octanoic acid (LPO) that bear all the hallmarks, including 5hmC profiles, of liver functionality. We exposed HLCs to LPO for 48 h to induce lipid accumulation. We characterized the transcriptome using RNA-seq, the metabolome using ultra-performance liquid chromatography-mass spectrometry and the epigenome using 5-hydroxymethylation DNA immunoprecipitation (hmeDIP) sequencing. LPO exposure induced an NAFLD phenotype in HLCs with transcriptional and metabolomic dysregulation consistent with those present in human NAFLD. HLCs maintain expression of the TET enzymes and have a liver-like epigenome. LPO exposure-induced 5hmC enrichment at lipid synthesis and transport genes. HLCs treated with LPO recapitulate the transcriptional and metabolic dysregulation seen in NAFLD and additionally retain TET expression and 5hmC. This in vitro model of NAFLD will be useful for future mechanistic and therapeutic studies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786564, year = {2018}, author = {Hagbard, L and Cameron, K and August, P and Penton, C and Parmar, M and Hay, DC and Kallur, T}, title = {Developing defined substrates for stem cell culture and differentiation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786564}, issn = {1471-2970}, abstract = {Over the past few decades, a variety of different reagents for stem cell maintenance and differentiation have been commercialized. These reagents share a common goal in facilitating the manufacture of products suitable for cell therapy while reducing the amount of non-defined components. Lessons from developmental biology have identified signalling molecules that can guide the differentiation process in vitro, but less attention has been paid to the extracellular matrix used. With the introduction of more biologically relevant and defined matrices, that better mimic specific cell niches, researchers now have powerful resources to fine-tune their in vitro differentiation systems, which may allow the manufacture of therapeutically relevant cell types. In this review article, we revisit the basics of the extracellular matrix, and explore the important role of the cell-matrix interaction. We focus on laminin proteins because they help to maintain pluripotency and drive cell fate specification.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786563, year = {2018}, author = {Iansante, V and Chandrashekran, A and Dhawan, A}, title = {Cell-based liver therapies: past, present and future.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786563}, issn = {1471-2970}, abstract = {Liver transplantation represents the standard treatment for people with an end-stage liver disease and some liver-based metabolic disorders; however, shortage of liver donor tissues limits its availability. Furthermore, whole liver replacement eliminates the possibility of using native liver as a possible target for future gene therapy in case of liver-based metabolic defects. Cell therapy has emerged as a potential alternative, as cells can provide the hepatic functions and engraft in the liver parenchyma. Various options have been proposed, including human or other species hepatocytes, hepatocyte-like cells derived from stem cells or more futuristic alternatives, such as combination therapies with different cell types, organoids and cell-biomaterial combinations. In this review, we aim to give an overview of the cell therapies developed so far, highlighting preclinical and/or clinical achievements as well as the limitations that need to be overcome to make them fully effective and safe for clinical applications.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786562, year = {2018}, author = {Williams, DP}, title = {Application of hepatocyte-like cells to enhance hepatic safety risk assessment in drug discovery.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786562}, issn = {1471-2970}, abstract = {Hepatic stress and injury from drugs continues to be a major concern within the pharmaceutical industry, leading to preclinical and clinical attrition precautionary warnings and post-market withdrawal of drugs. There is a requirement for more predictive and mechanistically accurate models to aid risk assessment. Primary human hepatocytes, subject to isolation stress, cryopreservation, donor-to-donor variation and a relatively short period of functional capability in two-dimensional cultures, are not suitable for high-throughput screening procedures. There are two areas within the drug discovery pipeline that the generation of a stable, metabolically functional hepatocyte-like cell with unlimited supply would have major impact. First, in routine, cell health risk-assessment assays where hepatic cell lines are typically deployed. Second, at later stages of the drug discovery pipeline approaching candidate nomination where bespoke/investigational studies refining and understanding the risk to patients use patient-derived induced pluripotent stem cell (iPSC) hepatocytes retaining characteristics from the patient, e.g. HLA susceptibility alleles, iPSC hepatocytes with defined disease phenotypes or genetic characteristics that have the potential to make the hepatocyte more sensitive to a particular stress mechanism. Functionality of patient-centric hepatocyte-like cells is likely to be enhanced when coupled with emerging culture systems, such as three-dimensional spheroids or microphysiological systems. Ultimately, the aspiration to confidently use human-relevant in vitro models to predict human-specific hepatic toxicity depends on the integration of promising emerging technologies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786561, year = {2018}, author = {Gamal, W and Wu, H and Underwood, I and Jia, J and Smith, S and Bagnaninchi, PO}, title = {Impedance-based cellular assays for regenerative medicine.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786561}, issn = {1471-2970}, abstract = {Therapies based on regenerative techniques have the potential to radically improve healthcare in the coming years. As a result, there is an emerging need for non-destructive and label-free technologies to assess the quality of engineered tissues and cell-based products prior to their use in the clinic. In parallel, the emerging regenerative medicine industry that aims to produce stem cells and their progeny on a large scale will benefit from moving away from existing destructive biochemical assays towards data-driven automation and control at the industrial scale. Impedance-based cellular assays (IBCA) have emerged as an alternative approach to study stem-cell properties and cumulative studies, reviewed here, have shown their potential to monitor stem-cell renewal, differentiation and maturation. They offer a novel method to non-destructively assess and quality-control stem-cell cultures. In addition, when combined with in vitro disease models they provide complementary insights as label-free phenotypic assays. IBCA provide quantitative and very sensitive results that can easily be automated and up-scaled in multi-well format. When facing the emerging challenge of real-time monitoring of three-dimensional cell culture dielectric spectroscopy and electrical impedance tomography represent viable alternatives to two-dimensional impedance sensing.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786560, year = {2018}, author = {Brown, GE and Khetani, SR}, title = {Microfabrication of liver and heart tissues for drug development.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786560}, issn = {1471-2970}, abstract = {Drug-induced liver- and cardiotoxicity remain among the leading causes of preclinical and clinical drug attrition, marketplace drug withdrawals and black-box warnings on marketed drugs. Unfortunately, animal testing has proven to be insufficient for accurately predicting drug-induced liver- and cardiotoxicity across many drug classes, likely due to significant differences in tissue functions across species. Thus, the field of in vitro human tissue engineering has gained increasing importance over the last 10 years. Technologies such as protein micropatterning, microfluidics, three-dimensional scaffolds and bioprinting have revolutionized in vitro platforms as well as increased the long-term phenotypic stability of both primary cells and stem cell-derived differentiated cells. Here, we discuss advances in engineering approaches for constructing in vitro human liver and heart models with utility for drug development. Design features and validation data of representative models are presented to highlight major trends followed by the discussion of pending issues. Overall, bioengineered liver and heart models have significantly advanced our understanding of organ function and injury, which will prove useful for mitigating the risk of drug-induced organ toxicity to human patients, reducing animal usage for preclinical drug testing, aiding in the discovery of novel therapeutics against human diseases, and ultimately for applications in regenerative medicine.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786559, year = {2018}, author = {Skeldon, G and Lucendo-Villarin, B and Shu, W}, title = {Three-dimensional bioprinting of stem-cell derived tissues for human regenerative medicine.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786559}, issn = {1471-2970}, abstract = {Stem cell technology in regenerative medicine has the potential to provide an unlimited supply of cells for drug testing, medical transplantation and academic research. In order to engineer a realistic tissue model using stem cells as an alternative to human tissue, it is essential to create artificial stem cell microenvironment or niches. Three-dimensional (3D) bioprinting is a promising tissue engineering field that offers new opportunities to precisely place stem cells within their niches layer-by-layer. This review covers bioprinting technologies, the current development of 'bio-inks' and how bioprinting has already been applied to stem-cell culture, as well as their applications for human regenerative medicine. The key considerations for bioink properties such as stiffness, stability and biodegradation, biocompatibility and printability are highlighted. Bioprinting of both adult and pluriopotent stem cells for various types of artificial tissues from liver to brain has been reviewed. 3D bioprinting of stem-cell derived tissues for human regenerative medicine is an exciting emerging area that represents opportunities for new research, industries and products as well as future challenges in clinical translation.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786558, year = {2018}, author = {Schmidt, S and Lilienkampf, A and Bradley, M}, title = {New substrates for stem cell control.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786558}, issn = {1471-2970}, abstract = {The capacity to culture stem cells in a controllable, robust and scalable manner is necessary in order to develop successful strategies for the generation of cellular and tissue platforms for drug screening, toxicity testing, tissue engineering and regenerative medicine. Creating substrates that support the expansion, maintenance or directional differentiation of stem cells would greatly aid these efforts. Optimally, the substrates used should be chemically defined and synthetically scalable, allowing growth under defined, serum-free culture conditions. To achieve this, the chemical and physical attributes of the substrates should mimic the natural tissue environment and allow control of their biological properties. Herein, recent advances in the development of materials to study/manipulate stem cells, both in vitro and in vivo, are described with a focus on the novelty of the substrates' properties, and on application of substrates to direct stem cells.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786557, year = {2018}, author = {Meisig, J and Blüthgen, N}, title = {The gene regulatory network of mESC differentiation: a benchmark for reverse engineering methods.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786557}, issn = {1471-2970}, abstract = {A large body of data have accumulated that characterize the gene regulatory network of stem cells. Yet, a comprehensive and integrative understanding of this complex network is lacking. Network reverse engineering methods that use transcriptome data to derive these networks may help to uncover the topology in an unbiased way. Many methods exist that use co-expression to reconstruct networks. However, it remains unclear how these methods perform in the context of stem cell differentiation, as most systematic assessments have been made for regulatory networks of unicellular organisms. Here, we report a systematic benchmark of different reverse engineering methods against functional data. We show that network pruning is critical for reconstruction performance. We also find that performance is similar for algorithms that use different co-expression measures, i.e. mutual information or correlation. In addition, different methods yield very different network topologies, highlighting the challenge of interpreting these resulting networks as a whole.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786556, year = {2018}, author = {Godoy, P and Schmidt-Heck, W and Hellwig, B and Nell, P and Feuerborn, D and Rahnenführer, J and Kattler, K and Walter, J and Blüthgen, N and Hengstler, JG}, title = {Assessment of stem cell differentiation based on genome-wide expression profiles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786556}, issn = {1471-2970}, abstract = {In recent years, protocols have been established to differentiate stem and precursor cells into more mature cell types. However, progress in this field has been hampered by difficulties to assess the differentiation status of stem cell-derived cells in an unbiased manner. Here, we present an analysis pipeline based on published data and methods to quantify the degree of differentiation and to identify transcriptional control factors explaining differences from the intended target cells or tissues. The pipeline requires RNA-Seq or gene array data of the stem cell starting population, derived 'mature' cells and primary target cells or tissue. It consists of a principal component analysis to represent global expression changes and to identify possible problems of the dataset that require special attention, such as: batch effects; clustering techniques to identify gene groups with similar features; over-representation analysis to characterize biological motifs and transcriptional control factors of the identified gene clusters; and metagenes as well as gene regulatory networks for quantitative cell-type assessment and identification of influential transcription factors. Possibilities and limitations of the analysis pipeline are illustrated using the example of human embryonic stem cell and human induced pluripotent cells to generate 'hepatocyte-like cells'. The pipeline quantifies the degree of incomplete differentiation as well as remaining stemness and identifies unwanted features, such as colon- and fibroblast-associated gene clusters that are absent in real hepatocytes but typically induced by currently available differentiation protocols. Finally, transcription factors responsible for incomplete and unwanted differentiation are identified. The proposed method is widely applicable and allows an unbiased and quantitative assessment of stem cell-derived cells.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786555, year = {2018}, author = {Fischer, L and Hay, DC and O'Farrelly, C}, title = {Innate immunity in stem cell-derived hepatocytes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786555}, issn = {1471-2970}, abstract = {Stem cell-derived hepatocyte-like cells (HLCs) offer great opportunities for studies of host-pathogen interactions and tissue regeneration, as well as hepatotoxicity. To reliably predict the outcome of infection or to enhance graft survival, a finely tuned innate immune system is essential. Hepatocytes have long been considered solely metabolic and their critical innate immune potential is only recently gaining attention. Viral infection studies show that pathogen detection by cytosolic receptors leads to interferon (IFN) induction in primary hepatocytes and HLCs. IFN expression in HLCs is characterized by strong expression of type III IFN and low expression of type I IFN which is also a characteristic of primary hepatocytes. The response to IFN differs in HLCs with lower interferon-stimulated gene (ISG)-expression levels than in primary hepatocytes. Tumour necrosis factor-alpha (TNF-α) signalling is less studied in HLCs, but appears to be functional. Expression of toll-like receptors (TLR) 2-5, 7 and 9 has been reported in primary hepatocytes but has been poorly studied in HLCs. In summary, although they retain some immature features, HLCs are in many ways superior to hepatoma cell lines for cell-based modelling. In this review, we will provide an overview of innate immune signalling in HLCs and how this compares with primary hepatocytes.This article is part of the themed issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786554, year = {2018}, author = {Lopez-Yrigoyen, M and Fidanza, A and Cassetta, L and Axton, RA and Taylor, AH and Meseguer-Ripolles, J and Tsakiridis, A and Wilson, V and Hay, DC and Pollard, JW and Forrester, LM}, title = {A human iPSC line capable of differentiating into functional macrophages expressing ZsGreen: a tool for the study and in vivo tracking of therapeutic cells.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786554}, issn = {1471-2970}, support = {MR/K011200/1//Medical Research Council/United Kingdom ; }, abstract = {We describe the production of a human induced pluripotent stem cell (iPSC) line, SFCi55-ZsGr, that has been engineered to express the fluorescent reporter gene, ZsGreen, in a constitutive manner. The CAG-driven ZsGreen expression cassette was inserted into the AAVS1 locus and a high level of expression was observed in undifferentiated iPSCs and in cell lineages derived from all three germ layers including haematopoietic cells, hepatocytes and neurons. We demonstrate efficient production of terminally differentiated macrophages from the SFCi55-ZsGreen iPSC line and show that they are indistinguishable from those generated from their parental SFCi55 iPSC line in terms of gene expression, cell surface marker expression and phagocytic activity. The high level of ZsGreen expression had no effect on the ability of macrophages to be activated to an M(LPS + IFNγ), M(IL10) or M(IL4) phenotype nor on their plasticity, assessed by their ability to switch from one phenotype to another. Thus, targeting of the AAVS1 locus in iPSCs allows for the production of fully functional, fluorescently tagged human macrophages that can be used for in vivo tracking in disease models. The strategy also provides a platform for the introduction of factors that are predicted to modulate and/or stabilize macrophage function.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786553, year = {2018}, author = {Tam, WL and Luyten, FP and Roberts, SJ}, title = {From skeletal development to the creation of pluripotent stem cell-derived bone-forming progenitors.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786553}, issn = {1471-2970}, abstract = {Bone has many functions. It is responsible for protecting the underlying soft organs, it allows locomotion, houses the bone marrow and stores minerals such as calcium and phosphate. Upon damage, bone tissue can efficiently repair itself. However, healing is hampered if the defect exceeds a critical size and/or is in compromised conditions. The isolation or generation of bone-forming progenitors has applicability to skeletal repair and may be used in tissue engineering approaches. Traditionally, bone engineering uses osteochondrogenic stem cells, which are combined with scaffold materials and growth factors. Despite promising preclinical data, limited translation towards the clinic has been observed to date. There may be several reasons for this including the lack of robust cell populations with favourable proliferative and differentiation capacities. However, perhaps the most pertinent reason is the failure to produce an implant that can replicate the developmental programme that is observed during skeletal repair. Pluripotent stem cells (PSCs) can potentially offer a solution for bone tissue engineering by providing unlimited cell sources at various stages of differentiation. In this review, we summarize key embryonic signalling pathways in bone formation coupled with PSC differentiation strategies for the derivation of bone-forming progenitors.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786552, year = {2018}, author = {Fair, KL and Colquhoun, J and Hannan, NRF}, title = {Intestinal organoids for modelling intestinal development and disease.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786552}, issn = {1471-2970}, abstract = {Gastrointestinal diseases are becoming increasingly prevalent in developed countries. Immortalized cells and animal models have delivered important but limited insight into the mechanisms that initiate and propagate these diseases. Human-specific models of intestinal development and disease are desperately needed that can recapitulate structure and function of the gut in vitro Advances in pluripotent stem cells and primary tissue culture techniques have made it possible to culture intestinal epithelial cells in three dimensions that self-assemble to form 'intestinal organoids'. These organoids allow for new, human-specific models that can be used to gain insight into gastrointestinal disease and potentially deliver new therapies to treat them. Here we review current in vitro models of intestinal development and disease, considering where improvements could be made and potential future applications in the fields of developmental modelling, drug/toxicity testing and therapeutic uses.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786551, year = {2018}, author = {Alhaque, S and Themis, M and Rashidi, H}, title = {Three-dimensional cell culture: from evolution to revolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786551}, issn = {1471-2970}, abstract = {Recent advances in the isolation of tissue-resident adult stem cells and the identification of inductive factors that efficiently direct differentiation of human pluripotent stem cells along specific lineages have facilitated the development of high-fidelity modelling of several tissues in vitro Many of the novel approaches have employed self-organizing three-dimensional (3D) culturing of organoids, which offer several advantages over conventional two-dimensional platforms. Organoid technologies hold great promise for modelling diseases and predicting the outcome of drug responses in vitro Here, we outline the historical background and some of the recent advances in the field of three-dimensional organoids. We also highlight some of the current limitations of these systems and discuss potential avenues to further benefit biological research using three-dimensional modelling technologies.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786550, year = {2018}, author = {McComish, SF and Caldwell, MA}, title = {Generation of defined neural populations from pluripotent stem cells.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786550}, issn = {1471-2970}, abstract = {Effective and efficient generation of human neural stem cells and subsequently functional neural populations from pluripotent stem cells has facilitated advancements in the study of human development and disease modelling. This review will discuss the established protocols for the generation of defined neural populations including regionalized neurons and astrocytes, oligodendrocytes and microglia. Early protocols were established in embryonic stem cells (ESC) but the discovery of induced pluripotent stem cells (iPSC) in 2006 provided a new platform for modelling human disorders of the central nervous system (CNS). The ability to produce patient- and disease-specific iPSC lines has created a new age of disease modelling. Human iPSC may be derived from adult somatic cells and subsequently patterned into numerous distinct cell types. The ability to derive defined and regionalized neural populations from iPSC provides a powerful in vitro model of CNS disorders.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786549, year = {2018}, author = {Abu-Dawud, R and Graffmann, N and Ferber, S and Wruck, W and Adjaye, J}, title = {Pluripotent stem cells: induction and self-renewal.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786549}, issn = {1471-2970}, abstract = {Pluripotent stem cells (PSCs) lie at the heart of modern regenerative medicine due to their properties of unlimited self-renewal in vitro and their ability to differentiate into cell types representative of the three embryonic germ layers-mesoderm, ectoderm and endoderm. The derivation of induced PSCs bypasses ethical concerns associated with the use of human embryonic stem cells and also enables personalized cell-based therapies. To exploit their regenerative potential, it is essential to have a firm understanding of the molecular processes associated with their induction from somatic cells. This understanding serves two purposes: first, to enable efficient, reliable and cost-effective production of excellent quality induced PSCs and, second, to enable the derivation of safe, good manufacturing practice-grade transplantable donor cells. Here, we review the reprogramming process of somatic cells into induced PSCs and associated mechanisms with emphasis on self-renewal, epigenetic control, mitochondrial bioenergetics, sub-states of pluripotency, naive ground state, naive and primed. A meta-analysis identified genes expressed exclusively in the inner cell mass and in the naive but not in the primed pluripotent state. We propose these as additional biomarkers defining naive PSCs.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786548, year = {2018}, author = {Hay, DC and O'Farrelly, C}, title = {Designer human tissue: coming to a lab near you.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1750}, pages = {}, pmid = {29786548}, issn = {1471-2970}, abstract = {Human pluripotent stem cells (PSCs) offer a scalable alternative to primary and transformed human tissue. PSCs include human embryonic stem cells, derived from the inner cell mass of blastocysts unsuitable for human implantation; and induced PSCs, generated by the reprogramming of somatic cells. Both cell types display the ability to self-renew and retain pluripotency, promising an unlimited supply of human somatic cells for biomedical application. A distinct advantage of using PSCs is the ability to select for genetic background, promising personalized modelling of human biology 'in a dish' or immune-matched cell-based therapies for the clinic. This special issue will guide the reader through stem cell self-renewal, pluripotency and differentiation. The first articles focus on improving cell fidelity, understanding the innate immune system and the importance of materials chemistry, biofabrication and bioengineering. These are followed by articles that focus on industrial application, commercialization and label-free assessment of tissue formation. The special issue concludes with an article discussing human liver cell-based therapies past, present and future.This article is part of the theme issue 'Designer human tissue: coming to a lab near you'.}, } @article {pmid29786505, year = {2018}, author = {Alba, DM and Casanovas-Vilar, I and Furió, M and García-Paredes, I and Angelone, C and Jovells-Vaqué, S and Luján, ÀH and Almécija, S and Moyà-Solà, S}, title = {Can Pallars i Llobateres: A new hominoid-bearing locality from the late Miocene of the Vallès-Penedès Basin (NE Iberian Peninsula).}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {193-203}, doi = {10.1016/j.jhevol.2018.04.008}, pmid = {29786505}, issn = {1095-8606}, abstract = {In the Iberian Peninsula, Miocene apes (Hominoidea) are generally rare and mostly restricted to the Vallès-Penedès Basin. Here we report a new hominoid maxillary fragment with M2 from this basin. It was surface-collected in March 2017 from the site of Can Pallars i Llobateres (CPL, Sant Quirze del Vallès), where fossil apes had not been previously recorded. The locality of provenance (CPL-M), which has delivered no further fossil remains, is located very close (ca. 50 m) to previously known CPL outcrops, and not very far (ca. 500 m in NW direction) from the classical hominoid-bearing locality of Can Poncic 1. Here we describe the new fossil and, based on the size and proportions of the M2, justify its taxonomic attribution to Hispanopithecus cf. laietanus, a species previously recorded from several Vallesian sites of the Vallès-Penedès Basin. Based on the associated mammalian fauna from CPL, we also provide a biochronological dating and a paleoenvironmental reconstruction for the site. The associated fauna enables an unambiguous correlation to the Cricetulodon hartenbergeri - Progonomys hispanicus interval local subzone, with an estimated age of 9.98-9.73 Ma (late Vallesian, MN10). Therefore, CPL-M is roughly coeval with the Hispanopithecus laietanus-bearing localities of Can Llobateres 1 and Can Feu 1, and minimally older than those of La Tarumba 1 and Can Llobateres 2. In contrast, CPL-M is younger than the early Vallesian (MN9) localities of Can Poncic 1 (the type locality of Hispanopithecus crusafonti) as well as Polinyà 2 (Gabarró) and Estació Depuradora d'Aigües Residuals-Riu Ripoll 13, where Hispanopithecus sp. is recorded. The associated fauna from CPL indicates a densely forested and humid paleoenvironment with nearby freshwater. This supports the view that Hispanopithecus might have been restricted to dense wetland forests soon before its extinction during the late Vallesian, due to progressive climatic deterioration. Coupled with the existence of other fossiliferous outcrops in the area, this find is most promising for the prospect of discovering additional fossil hominoid remains in the future.}, } @article {pmid29786499, year = {2018}, author = {Lopes, MR and Batista, TM and Franco, GR and Ribeiro, LR and Santos, ARO and Furtado, C and Moreira, RG and Goes-Neto, A and Vital, MJS and Rosa, LH and Lachance, MA and Rosa, CA}, title = {Scheffersomyces stambukii f.a., sp. nov., a d-xylose-fermenting species isolated from rotting wood.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2306-2312}, doi = {10.1099/ijsem.0.002834}, pmid = {29786499}, issn = {1466-5034}, mesh = {Brazil ; DNA, Fungal/genetics ; Fermentation ; Forests ; Mycological Typing Techniques ; *Phylogeny ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Wood/*microbiology ; Xylose/*metabolism ; }, abstract = {Two isolates representing a new species of Scheffersomyces were isolated from rotting wood samples collected in an Amazonian forest ecosystem in Brazil. Analysis of the sequences of the D1/D2 domains showed that this new species is phylogenetically related to Scheffersomyces NYMU 15730, a species without a formal description, and the two are in an early emerging position with respect to the xylose-fermenting subclade containing Scheffersomyces titanus and Scheffersomyces stipitis. Phylogenomic analyses using 474 orthologous genes placed the new species in an intermediary position between Scheffersomyces species and the larger genus Spathaspora and the Candida albicans/Lodderomyces clade. The novel species, Scheffersomyces stambukii f.a., sp. nov., is proposed to accommodate these isolates. The type strain of Scheffersomyces stambukii sp. nov. is UFMG-CM-Y427T (=CBS 14217T). The MycoBank number is MB 824093. In addition, we studied the xylose metabolism of this new species.}, } @article {pmid29786497, year = {2018}, author = {Ren, M and Li, X and Zhang, Y and Jin, Y and Li, S and Huang, H}, title = {Massilia armeniaca sp. nov., isolated from desert soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2319-2324}, doi = {10.1099/ijsem.0.002836}, pmid = {29786497}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; *Desert Climate ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Oxalobacteraceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, strain ZMN-3T, was isolated from desert soil sample collected from Ongniod Qi, Inner Mongolia, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain ZMN-3T was affiliated with the genus Massilia and showed the highest similarity to Massilia humi THG S6-8T (98.9 %) and Massilia buxea A9T (98.2 %). In partial gyrB and lepA sequences, the highest similarity of strain ZMN-3T and M. humi THG S6-8T were 95.9 and 96.8 %, respectively. The DNA-DNA hybridization value between strain ZMN-3T and its closely related type strains were all below 70 %. The major respiratory quinone of strain ZMN-3T was Q-8 and the major cellular fatty acids consisted of summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The predominant polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phospholipid. The DNA G+C content of strain ZMN-3T was 66.3 mol%. On the basis of this polyphasic taxonomic study, strain ZMN-3T is considered to represent a novel species of the genus Massilia, for which the name Massilia armeniaca sp. nov. is proposed. The type strain is ZMN-3T (=CGMCC 1.16209T=DSM 104676T).}, } @article {pmid29786171, year = {2018}, author = {Vigani, G and Rolli, E and Marasco, R and Dell'Orto, M and Michoud, G and Soussi, A and Raddadi, N and Borin, S and Sorlini, C and Zocchi, G and Daffonchio, D}, title = {Root bacterial endophytes confer drought resistance and enhance expression and activity of a vacuolar H+ -pumping pyrophosphatase in pepper plants.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14272}, pmid = {29786171}, issn = {1462-2920}, support = {RBIN047MBH//Italian MIUR FIRB/ ; 245746//European Community's Seventh Framework Programme/ ; //King Abdullah University of Science and Technology/ ; //Università degli Studi di Milano/ ; //DeFENS/ ; //Regione Lombardia/ ; }, abstract = {It has been previously shown that the transgenic overexpression of the plant root vacuolar proton pumps H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase) confer tolerance to drought. Since plant-root endophytic bacteria can also promote drought tolerance, we hypothesize that such promotion can be associated to the enhancement of the host vacuolar proton pumps expression and activity. To test this hypothesis, we selected two endophytic bacteria endowed with an array of in vitro plant growth promoting traits. Their genome sequences confirmed the presence of traits previously shown to confer drought resistance to plants, such as the synthesis of nitric oxide and of organic volatile organic compounds. We used the two strains on pepper (Capsicuum annuum L.) because of its high sensitivity to drought. Under drought conditions, both strains stimulated a larger root system and enhanced the leaves' photosynthetic activity. By testing the expression and activity of the vacuolar proton pumps, H+ -ATPase (V-ATPase) and H+ -PPase (V-PPase), we found that bacterial colonization enhanced V-PPase only. We conclude that the enhanced expression and activity of V-PPase can be favoured by the colonization of drought-tolerance-inducing bacterial endophytes.}, } @article {pmid29786169, year = {2018}, author = {Kieser, S and Sarker, SA and Sakwinska, O and Foata, F and Sultana, S and Khan, Z and Islam, S and Porta, N and Combremont, S and Betrisey, B and Fournier, C and Charpagne, A and Descombes, P and Mercenier, A and Berger, B and Brüssow, H}, title = {Bangladeshi children with acute diarrhoea show faecal microbiomes with increased Streptococcus abundance, irrespective of diarrhoea aetiology.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14274}, pmid = {29786169}, issn = {1462-2920}, abstract = {We report streptococcal dysbiosis in acute diarrhoea irrespective of aetiology. Compared with 20 healthy local controls, 71 Bangladeshi children hospitalized with acute diarrhoea (AD) of viral, mixed viral/bacterial, bacterial and unknown aetiology showed a significantly decreased bacterial diversity with loss of pathways characteristic for the healthy distal colon microbiome (mannan degradation, methylerythritol phosphate and thiamin biosynthesis), an increased proportion of faecal streptococci belonging to the Streptococcus bovis and Streptococcus salivarius species complexes, and an increased level of E. coli-associated virulence genes. No enteropathogens could be attributed to a subgroup of patients. Elevated lytic coliphage DNA was detected in 2 out of 5 investigated enteroaggregative E. coli (EAEC)-infected patients. Streptococcal outgrowth in AD is discussed as a potential nutrient-driven consequence of glucose provided with oral rehydration solution.}, } @article {pmid29786168, year = {2018}, author = {Lam, BR and Rowe, AR and Nealson, KH}, title = {Variation in electrode redox potential selects for different microorganisms under cathodic current flow from electrodes in marine sediments.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14275}, pmid = {29786168}, issn = {1462-2920}, abstract = {Extracellular electron transport (EET) is a microbial process that allows microorganisms to transport electrons to and from insoluble substrates outside of the cell. Although progress has been made in understanding how microbes transfer electrons to insoluble substrates, the process of receiving electrons has largely remained unexplored. We investigated redox potentials favourable for donating electrons to dissolved and insoluble components in Catalina Harbor marine sediment by combining electrochemical techniques with geochemistry and molecular methods. Working electrodes buried in sediment microcosms were poised at seven redox potentials between -300 and -750 mV versus Ag/AgCl using a three-electrode system. In electrode biofilms recovered after 2-month incubations, overall community diversity increased with more negative redox potentials. Abundances of known EET-capable groups (e.g., Alteromonadales and Desulfuromonadales) varied with redox potential. Motility and chemotaxis genes were found in greater abundance in electrode communities, suggesting a possible selective advantage of these pathways for colonization and utilization of the electrode. Our enrichments demonstrated the validity of this approach in capturing groups known, as well as novel groups (e.g., Campylobacterales) that perform EET. The diverse nature of the enriched cathode communities suggest that insoluble substrate oxidation may be a critical, although poorly described microbial metabolic process in marine sediment.}, } @article {pmid29785634, year = {2018}, author = {Obando S, TA and Babykin, MM and Zinchenko, VV}, title = {A Cluster of Five Genes Essential for the Utilization of Dihydroxamate Xenosiderophores in Synechocystis sp. PCC 6803.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1165-1173}, pmid = {29785634}, issn = {1432-0991}, support = {Project 13-04-01767//Russian Foundation for Basic Research/ ; }, mesh = {Anabaena variabilis/*metabolism ; Bacterial Proteins/genetics/metabolism ; Biological Transport/genetics ; Genetic Complementation Test ; Hydroxamic Acids/*metabolism ; INDEL Mutation ; Iron/metabolism ; Membrane Transport Proteins/*genetics/metabolism ; *Multigene Family ; Siderophores/*genetics/metabolism ; Synechocystis/*genetics ; }, abstract = {The unicellular freshwater cyanobacterium Synechocystis sp. PCC 6803 is capable of using dihydroxamate xenosiderophores, either ferric schizokinen (FeSK) or a siderophore of the filamentous cyanobacterium Anabaena variabilis ATCC 29413 (SAV), as the sole source of iron in the TonB-dependent manner. The fecCDEB1-schT gene cluster encoding a siderophore transport system that is involved in the utilization of FeSK and SAV in Synechocystis sp. PCC 6803 was identified. The gene schT encodes TonB-dependent outer membrane transporter, whereas the remaining four genes encode the ABC-type transporter FecB1CDE formed by the periplasmic binding protein FecB1, the transmembrane permease proteins FecC and FecD, and the ATPase FecE. Inactivation of any of these genes resulted in the inability of cells to utilize FeSK and SAV. Our data strongly suggest that Synechocystis sp. PCC 6803 can readily internalize Fe-siderophores via the classic TonB-dependent transport system.}, } @article {pmid29785633, year = {2018}, author = {Guo, M and Fang, Z and Sun, L and Sun, D and Wang, Y and Li, C and Wang, R and Liu, Y and Hu, H and Liu, Y and Xu, D and Gooneratne, R}, title = {Regulation of Thermostable Direct Hemolysin and Biofilm Formation of Vibrio parahaemolyticus by Quorum-Sensing Genes luxM and luxS.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1190-1197}, pmid = {29785633}, issn = {1432-0991}, support = {31371746//Natural Science Foundation of China/ ; GDOU2013050205//higher educational cultivation program for major scientific research projects of Guangdong Ocean University/ ; 2014050203//higher educational cultivation program for major scientific research projects of Guangdong Ocean University/ ; 2015ZZ02//the scientific research program of administration of quality and technology supervision of Guangdong province/ ; }, mesh = {Bacterial Proteins/genetics/metabolism ; Bacterial Toxins/genetics/metabolism ; Biofilms/*growth & development ; Gene Deletion ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial/*genetics ; Hemolysin Proteins/*genetics/metabolism ; Quorum Sensing/*genetics ; Transcription, Genetic ; Vibrio parahaemolyticus/*genetics/growth & development/metabolism ; Virulence/genetics ; }, abstract = {Vibrio parahaemolyticus is a seafood opportunistic pathogen. There are evidences suggesting that virulence skills, including hemolytic activity and biofilm formation, are regulated by the luxM/luxS-dependent quorum-sensing system in V. parahaemolyticus, and their regulatory mechanism is not well understood. To better understand the virulence regulatory mechanism of V. parahaemolyticus, the luxM deletion (△luxM) and luxS deletion (△luxS) mutants were constructed and their impacts on growth, hemolysin activity, and biofilm were investigated. Results show that both luxM and luxS are involved in the adaptation to environmental conditions in early adaptive-log phase growth of V. parahaemolyticus. Thermostable direct hemolysin gene (tdh) was negatively regulated by luxM and positively regulated by luxS. The biofilm formation was negatively regulated by both luxS and luxM. This study provides an insight into some aspects of V. parahaemolyticus virulence regulation by luxM/luxS-dependent quorum-sensing system.}, } @article {pmid29785632, year = {2018}, author = {Dos Santos, AMP and Ferrari, RG and Conte-Junior, CA}, title = {Virulence Factors in Salmonella Typhimurium: The Sagacity of a Bacterium.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1510-4}, pmid = {29785632}, issn = {1432-0991}, support = {E-26/201.185/2014//Faperj/ ; 232227//Faperj/ ; 311422/2016-0//CNPq/ ; 125//CAPES/Embrapa/ ; }, abstract = {Currently, Salmonella enterica Typhimurium (ST) is responsible for most cases of food poisoning in several countries. It is characterized as a non-specific zoonotic bacterium that can infect both humans and animals and although most of the infections caused by this microorganism cause only a self-limiting gastroenteritis, some ST strains have been shown to be invasive, crossing the intestinal wall and reaching the systemic circulation. This unusual pathogenicity ability is closely related to ST virulence factors. This review aims to portray the main virulence factors in Salmonella Typhimurium, in order to better understand the strategies that this pathogen uses to reach the systemic circulation and increase its infectivity in humans and animals. Thus, the most studied Salmonella pathogenicity islands in Salmonella Typhimurium were detailed as to the functions of their encoded virulence factors. In addition, available knowledge on virulence plasmid was also compiled, as well as the chromosome regions involved in the virulence of this bacterium.}, } @article {pmid29785052, year = {2018}, author = {Uchida, KI and Daimon, S and Iguchi, R and Saitoh, E}, title = {Observation of anisotropic magneto-Peltier effect in nickel.}, journal = {Nature}, volume = {558}, number = {7708}, pages = {95-99}, doi = {10.1038/s41586-018-0143-x}, pmid = {29785052}, issn = {1476-4687}, abstract = {The Peltier effect, discovered in 1834, converts a charge current into a heat current in a conductor, and its performance is described by the Peltier coefficient, which is defined as the ratio of the generated heat current to the applied charge current1,2. To exploit the Peltier effect for thermoelectric cooling or heating, junctions of two conductors with different Peltier coefficients have been believed to be indispensable. Here we challenge this conventional wisdom by demonstrating Peltier cooling and heating in a single material without junctions. This is realized through an anisotropic magneto-Peltier effect in which the Peltier coefficient depends on the angle between the directions of a charge current and magnetization in a ferromagnet. By using active thermography techniques3-10, we observe the temperature change induced by this effect in a plain nickel slab. We find that the thermoelectric properties of the ferromagnet can be redesigned simply by changing the configurations of the charge current and magnetization, for instance, by shaping the ferromagnet so that the current must flow around a curve. Our experimental results demonstrate the suitability of nickel for the anisotropic magneto-Peltier effect and the importance of spin-orbit interaction in its mechanism. The anisotropic magneto-Peltier effect observed here is the missing thermoelectric phenomenon in ferromagnetic materials-the Onsager reciprocal of the anisotropic magneto-Seebeck effect previously observed in ferromagnets-and its simplicity might prove useful in developing thermal management technologies for electronic and spintronic devices.}, } @article {pmid29785015, year = {2018}, author = {Holt, KE and McAdam, P and Thai, PVK and Thuong, NTT and Ha, DTM and Lan, NN and Lan, NH and Nhu, NTQ and Hai, HT and Ha, VTN and Thwaites, G and Edwards, DJ and Nath, AP and Pham, K and Ascher, DB and Farrar, J and Khor, CC and Teo, YY and Inouye, M and Caws, M and Dunstan, SJ}, title = {Frequent transmission of the Mycobacterium tuberculosis Beijing lineage and positive selection for the EsxW Beijing variant in Vietnam.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {849-856}, pmid = {29785015}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; 081814//Wellcome Trust/United Kingdom ; }, abstract = {To examine the transmission dynamics of Mycobacterium tuberculosis (Mtb) isolated from tuberculosis patients in Ho Chi Minh City, Vietnam, we sequenced the whole genomes of 1,635 isolates and compared these with 3,144 isolates from elsewhere. The data identify an underlying burden of disease caused by the endemic Mtb lineage 1 associated with the activation of long-term latent infection, and a threefold higher burden associated with the more recently introduced Beijing lineage and lineage 4 Mtb strains. We find that Beijing lineage Mtb is frequently transferred between Vietnam and other countries, and detect higher levels of transmission of Beijing lineage strains within this host population than the endemic lineage 1 Mtb. Screening for parallel evolution of Beijing lineage-associated SNPs in other Mtb lineages as a signal of positive selection, we identify an alteration in the ESX-5 type VII-secreted protein EsxW, which could potentially contribute to the enhanced transmission of Beijing lineage Mtb in Vietnamese and other host populations.}, } @article {pmid29785014, year = {2018}, author = {Park, HJ and Ji, P and Kim, S and Xia, Z and Rodriguez, B and Li, L and Su, J and Chen, K and Masamha, CP and Baillat, D and Fontes-Garfias, CR and Shyu, AB and Neilson, JR and Wagner, EJ and Li, W}, title = {3' UTR shortening represses tumor-suppressor genes in trans by disrupting ceRNA crosstalk.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {783-789}, doi = {10.1038/s41588-018-0118-8}, pmid = {29785014}, issn = {1546-1718}, support = {R01 HG007538/HG/NHGRI NIH HHS/United States ; }, abstract = {Widespread mRNA 3' UTR shortening through alternative polyadenylation 1 promotes tumor growth in vivo 2 . A prevailing hypothesis is that it induces proto-oncogene expression in cis through escaping microRNA-mediated repression. Here we report a surprising enrichment of 3'UTR shortening among transcripts that are predicted to act as competing-endogenous RNAs (ceRNAs) for tumor-suppressor genes. Our model-based analysis of the trans effect of 3' UTR shortening (MAT3UTR) reveals a significant role in altering ceRNA expression. MAT3UTR predicts many trans-targets of 3' UTR shortening, including PTEN, a crucial tumor-suppressor gene 3 involved in ceRNA crosstalk 4 with nine 3'UTR-shortening genes, including EPS15 and NFIA. Knockdown of NUDT21, a master 3' UTR-shortening regulator 2 , represses tumor-suppressor genes such as PHF6 and LARP1 in trans in a miRNA-dependent manner. Together, the results of our analysis suggest a major role of 3' UTR shortening in repressing tumor-suppressor genes in trans by disrupting ceRNA crosstalk, rather than inducing proto-oncogenes in cis.}, } @article {pmid29785013, year = {2018}, author = {Skene, NG and Bryois, J and Bakken, TE and Breen, G and Crowley, JJ and Gaspar, HA and Giusti-Rodriguez, P and Hodge, RD and Miller, JA and Muñoz-Manchado, AB and O'Donovan, MC and Owen, MJ and Pardiñas, AF and Ryge, J and Walters, JTR and Linnarsson, S and Lein, ES and , and Sullivan, PF and Hjerling-Leffler, J}, title = {Genetic identification of brain cell types underlying schizophrenia.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {825-833}, doi = {10.1038/s41588-018-0129-5}, pmid = {29785013}, issn = {1546-1718}, support = {U01 MH109514/MH/NIMH NIH HHS/United States ; }, abstract = {With few exceptions, the marked advances in knowledge about the genetic basis of schizophrenia have not converged on findings that can be confidently used for precise experimental modeling. By applying knowledge of the cellular taxonomy of the brain from single-cell RNA sequencing, we evaluated whether the genomic loci implicated in schizophrenia map onto specific brain cell types. We found that the common-variant genomic results consistently mapped to pyramidal cells, medium spiny neurons (MSNs) and certain interneurons, but far less consistently to embryonic, progenitor or glial cells. These enrichments were due to sets of genes that were specifically expressed in each of these cell types. We also found that many of the diverse gene sets previously associated with schizophrenia (genes involved in synaptic function, those encoding mRNAs that interact with FMRP, antipsychotic targets, etc.) generally implicated the same brain cell types. Our results suggest a parsimonious explanation: the common-variant genetic results for schizophrenia point at a limited set of neurons, and the gene sets point to the same cells. The genetic risk associated with MSNs did not overlap with that of glutamatergic pyramidal cells and interneurons, suggesting that different cell types have biologically distinct roles in schizophrenia.}, } @article {pmid29785012, year = {2018}, author = {Matreyek, KA and Starita, LM and Stephany, JJ and Martin, B and Chiasson, MA and Gray, VE and Kircher, M and Khechaduri, A and Dines, JN and Hause, RJ and Bhatia, S and Evans, WE and Relling, MV and Yang, W and Shendure, J and Fowler, DM}, title = {Multiplex assessment of protein variant abundance by massively parallel sequencing.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {874-882}, pmid = {29785012}, issn = {1546-1718}, support = {R24 GM115277/GM/NIGMS NIH HHS/United States ; R01 CA096670/CA/NCI NIH HHS/United States ; T32 GM007454/GM/NIGMS NIH HHS/United States ; R01 GM109110/GM/NIGMS NIH HHS/United States ; P30 CA021765/CA/NCI NIH HHS/United States ; DP1 HG007811/HG/NHGRI NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; P50 GM115279/GM/NIGMS NIH HHS/United States ; }, abstract = {Determining the pathogenicity of genetic variants is a critical challenge, and functional assessment is often the only option. Experimentally characterizing millions of possible missense variants in thousands of clinically important genes requires generalizable, scalable assays. We describe variant abundance by massively parallel sequencing (VAMP-seq), which measures the effects of thousands of missense variants of a protein on intracellular abundance simultaneously. We apply VAMP-seq to quantify the abundance of 7,801 single-amino-acid variants of PTEN and TPMT, proteins in which functional variants are clinically actionable. We identify 1,138 PTEN and 777 TPMT variants that result in low protein abundance, and may be pathogenic or alter drug metabolism, respectively. We observe selection for low-abundance PTEN variants in cancer, and show that p.Pro38Ser, which accounts for ~10% of PTEN missense variants in melanoma, functions via a dominant-negative mechanism. Finally, we demonstrate that VAMP-seq is applicable to other genes, highlighting its generalizability.}, } @article {pmid29785011, year = {2018}, author = {Zhu, Z and Lee, PH and Chaffin, MD and Chung, W and Loh, PR and Lu, Q and Christiani, DC and Liang, L}, title = {A genome-wide cross-trait analysis from UK Biobank highlights the shared genetic architecture of asthma and allergic diseases.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {857-864}, pmid = {29785011}, issn = {1546-1718}, support = {R00 MH101367/MH/NIMH NIH HHS/United States ; R01 HL060710/HL/NHLBI NIH HHS/United States ; R01 HL114769/HL/NHLBI NIH HHS/United States ; R56 HL134356/HL/NHLBI NIH HHS/United States ; }, abstract = {Clinical and epidemiological data suggest that asthma and allergic diseases are associated and may share a common genetic etiology. We analyzed genome-wide SNP data for asthma and allergic diseases in 33,593 cases and 76,768 controls of European ancestry from UK Biobank. Two publicly available independent genome-wide association studies were used for replication. We have found a strong genome-wide genetic correlation between asthma and allergic diseases (rg = 0.75, P = 6.84 × 10-62). Cross-trait analysis identified 38 genome-wide significant loci, including 7 novel shared loci. Computational analysis showed that shared genetic loci are enriched in immune/inflammatory systems and tissues with epithelium cells. Our work identifies common genetic architectures shared between asthma and allergy and will help to advance understanding of the molecular mechanisms underlying co-morbid asthma and allergic diseases.}, } @article {pmid29785010, year = {2018}, author = {Khawaja, AP and Cooke Bailey, JN and Wareham, NJ and Scott, RA and Simcoe, M and Igo, RP and Song, YE and Wojciechowski, R and Cheng, CY and Khaw, PT and Pasquale, LR and Haines, JL and Foster, PJ and Wiggs, JL and Hammond, CJ and Hysi, PG and , and , }, title = {Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {778-782}, pmid = {29785010}, issn = {1546-1718}, support = {R01 EY011671/EY/NEI NIH HHS/United States ; U01 HG004728/HG/NHGRI NIH HHS/United States ; U01 HG004446/HG/NHGRI NIH HHS/United States ; R21 EY028671/EY/NEI NIH HHS/United States ; UL1 TR000427/TR/NCATS NIH HHS/United States ; R01 EY011008/EY/NEI NIH HHS/United States ; P01 CA087969/CA/NCI NIH HHS/United States ; R01 HL043851/HL/NHLBI NIH HHS/United States ; P01 HL073042/HL/NHLBI NIH HHS/United States ; G1000143//Medical Research Council/United Kingdom ; U01 HG004424/HG/NHGRI NIH HHS/United States ; R01 HL073389/HL/NHLBI NIH HHS/United States ; R01 EY023242/EY/NEI NIH HHS/United States ; MC_UU_12015/1//Medical Research Council/United Kingdom ; R01 EY012118/EY/NEI NIH HHS/United States ; R01 EY015543/EY/NEI NIH HHS/United States ; R56 EY011671/EY/NEI NIH HHS/United States ; U01 HG006389/HG/NHGRI NIH HHS/United States ; R01 EY008208/EY/NEI NIH HHS/United States ; R01 EY013178/EY/NEI NIH HHS/United States ; R01 EY019126/EY/NEI NIH HHS/United States ; R03 EY015682/EY/NEI NIH HHS/United States ; R01 EY022305/EY/NEI NIH HHS/United States ; P20 RR015574/RR/NCRR NIH HHS/United States ; UM1 CA186107/CA/NCI NIH HHS/United States ; R01 EY015473/EY/NEI NIH HHS/United States ; R01 CA047988/CA/NCI NIH HHS/United States ; R01 HL080467/HL/NHLBI NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; R01 EY009580/EY/NEI NIH HHS/United States ; //Wellcome Trust/United Kingdom ; U10 EY012118/EY/NEI NIH HHS/United States ; 094791//Wellcome Trust/United Kingdom ; R01 CA049449/CA/NCI NIH HHS/United States ; R01 CA131332/CA/NCI NIH HHS/United States ; P30 EY014104/EY/NEI NIH HHS/United States ; R01 EY015872/EY/NEI NIH HHS/United States ; R01 EY009847/EY/NEI NIH HHS/United States ; R01 EY010886/EY/NEI NIH HHS/United States ; U01 CA049449/CA/NCI NIH HHS/United States ; U01 HG004608/HG/NHGRI NIH HHS/United States ; R01 EY013315/EY/NEI NIH HHS/United States ; R01 EY018660/EY/NEI NIH HHS/United States ; }, abstract = {Glaucoma is the leading cause of irreversible blindness globally 1 . Despite its gravity, the disease is frequently undiagnosed in the community 2 . Raised intraocular pressure (IOP) is the most important risk factor for primary open-angle glaucoma (POAG)3,4. Here we present a meta-analysis of 139,555 European participants, which identified 112 genomic loci associated with IOP, 68 of which are novel. These loci suggest a strong role for angiopoietin-receptor tyrosine kinase signaling, lipid metabolism, mitochondrial function and developmental processes underlying risk for elevated IOP. In addition, 48 of these loci were nominally associated with glaucoma in an independent cohort, 14 of which were significant at a Bonferroni-corrected threshold. Regression-based glaucoma-prediction models had an area under the receiver operating characteristic curve (AUROC) of 0.76 in US NEIGHBORHOOD study participants and 0.74 in independent glaucoma cases from the UK Biobank. Genetic-prediction models for POAG offer an opportunity to target screening and timely therapy to individuals most at risk.}, } @article {pmid29784982, year = {2018}, author = {Ecker, M and Brink, JS and Rossouw, L and Chazan, M and Horwitz, LK and Lee-Thorp, JA}, title = {The palaeoecological context of the Oldowan-Acheulean in southern Africa.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1080-1086}, doi = {10.1038/s41559-018-0560-0}, pmid = {29784982}, issn = {2397-334X}, abstract = {The influence of climatic and environmental change on human evolution in the Pleistocene epoch is understood largely from extensive East African stable isotope records. These records show increasing proportions of C4 plants in the Early Pleistocene. We know far less about the expansion of C4 grasses at higher latitudes, which were also occupied by early Homo but are more marginal for C4 plants. Here we show that both C3 and C4 grasses and prolonged wetlands remained major components of Early Pleistocene environments in the central interior of southern Africa, based on enamel stable carbon and oxygen isotope data and associated faunal abundance and phytolith evidence from the site of Wonderwerk Cave. Vegetation contexts associated with Oldowan and early Acheulean lithic industries, in which climate is driven by an interplay of regional rainfall seasonality together with global CO2 levels, develop along a regional distinct trajectory compared to eastern South Africa and East Africa.}, } @article {pmid29784981, year = {2018}, author = {Giraudeau, M and Sepp, T and Ujvari, B and Ewald, PW and Thomas, F}, title = {Human activities might influence oncogenic processes in wild animal populations.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1065-1070}, doi = {10.1038/s41559-018-0558-7}, pmid = {29784981}, issn = {2397-334X}, abstract = {Based on the abundant studies available on humans showing clear associations between rapid environmental changes and the rate of neoplasia, we propose that human activities might increase cancer rate in wild populations through numerous processes. Most of the research on this topic has concentrated on wildlife cancer prevalence in environments that are heavily contaminated with anthropogenic chemicals. Here, we propose that human activities might also increase cancer rate in wild populations through additional processes including light pollution, accidental (for example, human waste) or intentional (for example, bird feeders) wildlife feeding (and the associated change of diet), or reduction of genetic diversity in human-impacted habitats. The human species can thus be defined as an oncogenic species, moderating the environment in the way that it causes cancer in other wild populations. As human impacts on wildlife are predicted to increase rather than decrease (for example, in the context of urbanization), acknowledging the possible links between human activity and cancer in wild populations is crucial.}, } @article {pmid29784980, year = {2018}, author = {Mazor, T and Doropoulos, C and Schwarzmueller, F and Gladish, DW and Kumaran, N and Merkel, K and Di Marco, M and Gagic, V}, title = {Global mismatch of policy and research on drivers of biodiversity loss.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1071-1074}, doi = {10.1038/s41559-018-0563-x}, pmid = {29784980}, issn = {2397-334X}, abstract = {The United Nations 2030 Agenda for Sustainable Development calls for urgent actions to reduce global biodiversity loss. Here, we synthesize >44,000 articles published in the past decade to assess the research focus on global drivers of loss. Relative research efforts on different drivers are not well aligned with their assessed impact, and multiple driver interactions are hardly considered. Research on drivers of biodiversity loss needs urgent realignment to match predicted severity and inform policy goals.}, } @article {pmid29784979, year = {2018}, author = {Wu, DD and Ding, XD and Wang, S and Wójcik, JM and Zhang, Y and Tokarska, M and Li, Y and Wang, MS and Faruque, O and Nielsen, R and Zhang, Q and Zhang, YP}, title = {Pervasive introgression facilitated domestication and adaptation in the Bos species complex.}, journal = {Nature ecology & evolution}, volume = {2}, number = {7}, pages = {1139-1145}, doi = {10.1038/s41559-018-0562-y}, pmid = {29784979}, issn = {2397-334X}, abstract = {Species of the Bos genus, including taurine cattle, zebu, gayal, gaur, banteng, yak, wisent and bison, have been domesticated at least four times and have been an important source of meat, milk and power for many human cultures. We sequence the genomes of gayal, gaur, banteng, wisent and bison, and provide population genomic sequencing of an additional 98 individuals. We use these data to determine the phylogeny and evolutionary history of these species and show that the threatened gayal is an independent species or subspecies. We show that there has been pronounced introgression among different members of this genus, and that it in many cases has involved genes of considerable adaptive importance. For example, genes under domestication selection in cattle (for example, MITF) were introgressed from domestic cattle to yak. Also, genes in the response-to-hypoxia pathway (for example, EGLN1, EGLN2 and HIF3a) have been introgressed from yak to Tibetan cattle, probably facilitating their adaptation to high altitude. We also validate that there is an association between the introgressed EGLN1 allele and haemoglobin and red blood cell concentration. Our results illustrate the importance of introgression as a source of adaptive variation and during domestication, and suggest that the Bos genus evolves as a complex of genetically interconnected species with shared evolutionary trajectories.}, } @article {pmid29784978, year = {2018}, author = {Otto, TD and Gilabert, A and Crellen, T and Böhme, U and Arnathau, C and Sanders, M and Oyola, SO and Okouga, AP and Boundenga, L and Willaume, E and Ngoubangoye, B and Moukodoum, ND and Paupy, C and Durand, P and Rougeron, V and Ollomo, B and Renaud, F and Newbold, C and Berriman, M and Prugnolle, F}, title = {Genomes of all known members of a Plasmodium subgenus reveal paths to virulent human malaria.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {687-697}, pmid = {29784978}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; 104792//Wellcome Trust/United Kingdom ; 206194//Wellcome Trust/United Kingdom ; }, abstract = {Plasmodium falciparum, the most virulent agent of human malaria, shares a recent common ancestor with the gorilla parasite Plasmodium praefalciparum. Little is known about the other gorilla- and chimpanzee-infecting species in the same (Laverania) subgenus as P. falciparum, but none of them are capable of establishing repeated infection and transmission in humans. To elucidate underlying mechanisms and the evolutionary history of this subgenus, we have generated multiple genomes from all known Laverania species. The completeness of our dataset allows us to conclude that interspecific gene transfers, as well as convergent evolution, were important in the evolution of these species. Striking copy number and structural variations were observed within gene families and one, stevor, shows a host-specific sequence pattern. The complete genome sequence of the closest ancestor of P. falciparum enables us to estimate the timing of the beginning of speciation to be 40,000-60,000 years ago followed by a population bottleneck around 4,000-6,000 years ago. Our data allow us also to search in detail for the features of P. falciparum that made it the only member of the Laverania able to infect and spread in humans.}, } @article {pmid29784977, year = {2018}, author = {Tian, X and He, GJ and Hu, P and Chen, L and Tao, C and Cui, YL and Shen, L and Ke, W and Xu, H and Zhao, Y and Xu, Q and Bai, F and Wu, B and Yang, E and Lin, X and Wang, L}, title = {Cryptococcus neoformans sexual reproduction is controlled by a quorum sensing peptide.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {698-707}, doi = {10.1038/s41564-018-0160-4}, pmid = {29784977}, issn = {2058-5276}, abstract = {Bacterial quorum sensing is a well-characterized communication system that governs a large variety of collective behaviours. By comparison, quorum sensing regulation in eukaryotic microbes remains poorly understood, especially its functional role in eukaryote-specific behaviours, such as sexual reproduction. Cryptococcus neoformans is a prevalent fungal pathogen that has two defined sexual cycles (bisexual and unisexual) and is a model organism for studying sexual reproduction in fungi. Here, we show that the quorum sensing peptide Qsp1 serves as an important signalling molecule for both forms of sexual reproduction. Qsp1 orchestrates various differentiation and molecular processes, including meiosis, the hallmark of sexual reproduction. It activates bisexual mating, at least in part through the control of pheromone, a signal necessary for bisexual activation. Notably, Qsp1 also plays a major role in the intercellular regulation of unisexual initiation and coordination, in which pheromone is not strictly required. Through a multi-layered genetic screening approach, we identified the atypical zinc finger regulator Cqs2 as an important component of the Qsp1 signalling cascade during both bisexual and unisexual reproduction. The absence of Cqs2 eliminates the Qsp1-stimulated mating response. Together, these findings extend the range of behaviours governed by quorum sensing to sexual development and meiosis.}, } @article {pmid29784976, year = {2018}, author = {Kleerebezem, M}, title = {Microbial metabolic gatekeeping in the jejunum.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {650-651}, doi = {10.1038/s41564-018-0172-0}, pmid = {29784976}, issn = {2058-5276}, } @article {pmid29784975, year = {2018}, author = {Chetrit, D and Hu, B and Christie, PJ and Roy, CR and Liu, J}, title = {A unique cytoplasmic ATPase complex defines the Legionella pneumophila type IV secretion channel.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {678-686}, pmid = {29784975}, issn = {2058-5276}, support = {R01 AI087946/AI/NIAID NIH HHS/United States ; R01 GM107629/GM/NIGMS NIH HHS/United States ; R21 AI130671/AI/NIAID NIH HHS/United States ; R37 AI041699/AI/NIAID NIH HHS/United States ; }, abstract = {Type IV secretion systems (T4SSs) are complex machines used by bacteria to deliver protein and DNA complexes into target host cells1-5. Conserved ATPases are essential for T4SS function, but how they coordinate their activities to promote substrate transfer remains poorly understood. Here, we show that the DotB ATPase associates with the Dot-Icm T4SS at the Legionella cell pole through interactions with the DotO ATPase. The structure of the Dot-Icm apparatus was solved in situ by cryo-electron tomography at 3.5 nm resolution and the cytoplasmic complex was solved at 3.0 nm resolution. These structures revealed a cell envelope-spanning channel that connects to the cytoplasmic complex. Further analysis revealed a hexameric assembly of DotO dimers associated with the inner membrane complex, and a DotB hexamer associated with the base of this cytoplasmic complex. The assembly of a DotB-DotO energy complex creates a cytoplasmic channel that directs the translocation of substrates through the T4SS. These data define distinct stages in Dot-Icm machine biogenesis, advance our understanding of channel activation, and identify an envelope-spanning T4SS channel.}, } @article {pmid29784974, year = {2018}, author = {Zanoni, M and Palesch, D and Silvestri, G}, title = {Longing for HIV protection.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {648-649}, doi = {10.1038/s41564-018-0169-8}, pmid = {29784974}, issn = {2058-5276}, support = {P51 OD011132/OD/NIH HHS/United States ; }, } @article {pmid29784960, year = {2018}, author = {Koch, L}, title = {Some like it hot - sex determination in turtles.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {402-403}, doi = {10.1038/s41576-018-0023-0}, pmid = {29784960}, issn = {1471-0064}, } @article {pmid29784831, year = {2018}, author = {Conley, D and Zhang, S}, title = {The promise of genes for understanding cause and effect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5626-5628}, pmid = {29784831}, issn = {1091-6490}, mesh = {*Comprehension ; *Genetic Predisposition to Disease ; Humans ; }, } @article {pmid29784830, year = {2018}, author = {Toleman, CA and Schumacher, MA and Yu, SH and Zeng, W and Cox, NJ and Smith, TJ and Soderblom, EJ and Wands, AM and Kohler, JJ and Boyce, M}, title = {Structural basis of O-GlcNAc recognition by mammalian 14-3-3 proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5956-5961}, doi = {10.1073/pnas.1722437115}, pmid = {29784830}, issn = {1091-6490}, support = {R01 GM118847/GM/NIGMS NIH HHS/United States ; R21 DK112733/DK/NIDDK NIH HHS/United States ; UL1 TR001117/TR/NCATS NIH HHS/United States ; }, mesh = {14-3-3 Proteins/*chemistry/*metabolism ; Acetylglucosamine/*chemistry/*metabolism ; HEK293 Cells ; Humans ; Mass Spectrometry ; Models, Molecular ; Phosphopyruvate Hydratase/chemistry/metabolism ; Proteomics ; }, abstract = {O-GlcNAc is an intracellular posttranslational modification that governs myriad cell biological processes and is dysregulated in human diseases. Despite this broad pathophysiological significance, the biochemical effects of most O-GlcNAcylation events remain uncharacterized. One prevalent hypothesis is that O-GlcNAc moieties may be recognized by "reader" proteins to effect downstream signaling. However, no general O-GlcNAc readers have been identified, leaving a considerable gap in the field. To elucidate O-GlcNAc signaling mechanisms, we devised a biochemical screen for candidate O-GlcNAc reader proteins. We identified several human proteins, including 14-3-3 isoforms, that bind O-GlcNAc directly and selectively. We demonstrate that 14-3-3 proteins bind O-GlcNAc moieties in human cells, and we present the structures of 14-3-3β/α and γ bound to glycopeptides, providing biophysical insights into O-GlcNAc-mediated protein-protein interactions. Because 14-3-3 proteins also bind to phospho-serine and phospho-threonine, they may integrate information from O-GlcNAc and O-phosphate signaling pathways to regulate numerous physiological functions.}, } @article {pmid29784829, year = {2018}, author = {Sonawane, PD and Heinig, U and Panda, S and Gilboa, NS and Yona, M and Kumar, SP and Alkan, N and Unger, T and Bocobza, S and Pliner, M and Malitsky, S and Tkachev, M and Meir, S and Rogachev, I and Aharoni, A}, title = {Short-chain dehydrogenase/reductase governs steroidal specialized metabolites structural diversity and toxicity in the genus Solanum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5419-E5428}, pmid = {29784829}, issn = {1091-6490}, mesh = {Alkaloids/*biosynthesis/chemistry ; Gene Expression Regulation, Plant/genetics ; Glycosides/biosynthesis/chemistry ; Lycopersicon esculentum/enzymology/genetics/metabolism ; Oxidoreductases/metabolism ; Plant Extracts/chemistry ; Plants, Genetically Modified/metabolism ; Saponins/*biosynthesis/chemistry/metabolism ; Solanaceae/*chemistry/metabolism ; Steroids/chemistry ; Tomatine/analogs & derivatives/metabolism ; }, abstract = {Thousands of specialized, steroidal metabolites are found in a wide spectrum of plants. These include the steroidal glycoalkaloids (SGAs), produced primarily by most species of the genus Solanum, and metabolites belonging to the steroidal saponins class that are widespread throughout the plant kingdom. SGAs play a protective role in plants and have potent activity in mammals, including antinutritional effects in humans. The presence or absence of the double bond at the C-5,6 position (unsaturated and saturated, respectively) creates vast structural diversity within this metabolite class and determines the degree of SGA toxicity. For many years, the elimination of the double bond from unsaturated SGAs was presumed to occur through a single hydrogenation step. In contrast to this prior assumption, here, we show that the tomato GLYCOALKALOID METABOLISM25 (GAME25), a short-chain dehydrogenase/reductase, catalyzes the first of three prospective reactions required to reduce the C-5,6 double bond in dehydrotomatidine to form tomatidine. The recombinant GAME25 enzyme displayed 3β-hydroxysteroid dehydrogenase/Δ5,4 isomerase activity not only on diverse steroidal alkaloid aglycone substrates but also on steroidal saponin aglycones. Notably, GAME25 down-regulation rerouted the entire tomato SGA repertoire toward the dehydro-SGAs branch rather than forming the typically abundant saturated α-tomatine derivatives. Overexpressing the tomato GAME25 in the tomato plant resulted in significant accumulation of α-tomatine in ripe fruit, while heterologous expression in cultivated eggplant generated saturated SGAs and atypical saturated steroidal saponin glycosides. This study demonstrates how a single scaffold modification of steroidal metabolites in plants results in extensive structural diversity and modulation of product toxicity.}, } @article {pmid29784828, year = {2018}, author = {Bobay, LM and Ochman, H}, title = {Biological species in the viral world.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6040-6045}, pmid = {29784828}, issn = {1091-6490}, support = {R35 GM118038/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteriophages/*genetics ; Biological Evolution ; Genetic Speciation ; Genome, Viral/genetics ; Host Specificity/genetics ; Phylogeny ; *Species Specificity ; Virus Diseases/genetics ; Viruses/*genetics ; }, abstract = {Due to their dependence on cellular organisms for metabolism and replication, viruses are typically named and assigned to species according to their genome structure and the original host that they infect. But because viruses often infect multiple hosts and the numbers of distinct lineages within a host can be vast, their delineation into species is often dictated by arbitrary sequence thresholds, which are highly inconsistent across lineages. Here we apply an approach to determine the boundaries of viral species based on the detection of gene flow within populations, thereby defining viral species according to the biological species concept (BSC). Despite the potential for gene transfer between highly divergent genomes, viruses, like the cellular organisms they infect, assort into reproductively isolated groups and can be organized into biological species. This approach revealed that BSC-defined viral species are often congruent with the taxonomic partitioning based on shared gene contents and host tropism, and that bacteriophages can similarly be classified in biological species. These results open the possibility to use a single, universal definition of species that is applicable across cellular and acellular lifeforms.}, } @article {pmid29784827, year = {2018}, author = {}, title = {Correction for Li et al., Gαi1 and Gαi3 regulate macrophage polarization by forming a complex containing CD14 and Gab1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5252}, doi = {10.1073/pnas.1807268115}, pmid = {29784827}, issn = {1091-6490}, } @article {pmid29784826, year = {2018}, author = {Bhouri, M and Morishita, W and Temkin, P and Goswami, D and Kawabe, H and Brose, N and Südhof, TC and Craig, AM and Siddiqui, TJ and Malenka, R}, title = {Deletion of LRRTM1 and LRRTM2 in adult mice impairs basal AMPA receptor transmission and LTP in hippocampal CA1 pyramidal neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5382-E5389}, pmid = {29784826}, issn = {1091-6490}, support = {84241//CIHR/Canada ; R37 MH052804/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; FDN-143206//CIHR/Canada ; P50 MH086403/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; CA1 Region, Hippocampal/metabolism/*physiology ; Dendritic Spines/metabolism ; Excitatory Postsynaptic Potentials/physiology ; Long-Term Potentiation/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neural Cell Adhesion Molecules/*deficiency/genetics/metabolism ; Neurons/metabolism ; Pyramidal Cells/metabolism/*physiology ; Receptors, AMPA/genetics/*metabolism ; Receptors, N-Methyl-D-Aspartate/metabolism ; Synapses/metabolism ; Synaptic Transmission/physiology ; }, abstract = {Leucine-rich repeat transmembrane (LRRTM) proteins are synaptic cell adhesion molecules that influence synapse formation and function. They are genetically associated with neuropsychiatric disorders, and via their synaptic actions likely regulate the establishment and function of neural circuits in the mammalian brain. Here, we take advantage of the generation of a LRRTM1 and LRRTM2 double conditional knockout mouse (LRRTM1,2 cKO) to examine the role of LRRTM1,2 at mature excitatory synapses in hippocampal CA1 pyramidal neurons. Genetic deletion of LRRTM1,2 in vivo in CA1 neurons using Cre recombinase-expressing lentiviruses dramatically impaired long-term potentiation (LTP), an impairment that was rescued by simultaneous expression of LRRTM2, but not LRRTM4. Mutation or deletion of the intracellular tail of LRRTM2 did not affect its ability to rescue LTP, while point mutations designed to impair its binding to presynaptic neurexins prevented rescue of LTP. In contrast to previous work using shRNA-mediated knockdown of LRRTM1,2, KO of these proteins at mature synapses also caused a decrease in AMPA receptor-mediated, but not NMDA receptor-mediated, synaptic transmission and had no detectable effect on presynaptic function. Imaging of recombinant photoactivatable AMPA receptor subunit GluA1 in the dendritic spines of cultured neurons revealed that it was less stable in the absence of LRRTM1,2. These results illustrate the advantages of conditional genetic deletion experiments for elucidating the function of endogenous synaptic proteins and suggest that LRRTM1,2 proteins help stabilize synaptic AMPA receptors at mature spines during basal synaptic transmission and LTP.}, } @article {pmid29784825, year = {2018}, author = {Elsen, PR and Monahan, WB and Merenlender, AM}, title = {Global patterns of protection of elevational gradients in mountain ranges.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6004-6009}, pmid = {29784825}, issn = {1091-6490}, abstract = {Protected areas (PAs) that span elevational gradients enhance protection for taxonomic and phylogenetic diversity and facilitate species range shifts under climate change. We quantified the global protection of elevational gradients by analyzing the elevational distributions of 44,155 PAs in 1,010 mountain ranges using the highest resolution digital elevation models available. We show that, on average, mountain ranges in Africa and Asia have the lowest elevational protection, ranges in Europe and South America have intermediate elevational protection, and ranges in North America and Oceania have the highest elevational protection. We use the Convention on Biological Diversity's Aichi Target 11 to assess the proportion of elevational gradients meeting the 17% suggested minimum target and examine how different protection categories contribute to elevational protection. When considering only strict PAs [International Union for Conservation of Nature (IUCN) categories I-IV, n = 24,706], nearly 40% of ranges do not contain any PAs, roughly half fail to meet the 17% target at any elevation, and ∼75% fail to meet the target throughout ≥50% of the elevational gradient. Observed elevational protection is well below optimal, and frequently below a null model of elevational protection. Including less stringent PAs (IUCN categories V-VI and nondesignated PAs, n = 19,449) significantly enhances elevational protection for most continents, but several highly biodiverse ranges require new or expanded PAs to increase elevational protection. Ensuring conservation outcomes for PAs with lower IUCN designations as well as strategically placing PAs to better represent and connect elevational gradients will enhance ecological representation and facilitate species range shifts under climate change.}, } @article {pmid29784824, year = {2018}, author = {Hao, R and Fan, Y and Howard, MD and Vaughan, JC and Zhang, B}, title = {Imaging nanobubble nucleation and hydrogen spillover during electrocatalytic water splitting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5878-5883}, pmid = {29784824}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Nucleation and growth of hydrogen nanobubbles are key initial steps in electrochemical water splitting. These processes remain largely unexplored due to a lack of proper tools to probe the nanobubble's interfacial structure with sufficient spatial and temporal resolution. We report the use of superresolution microscopy to image transient formation and growth of single hydrogen nanobubbles at the electrode/solution interface during electrocatalytic water splitting. We found hydrogen nanobubbles can be generated even at very early stages in water electrolysis, i.e., ∼500 mV before reaching its thermodynamic reduction potential. The ability to image single nanobubbles on an electrode enabled us to observe in real time the process of hydrogen spillover from ultrathin gold nanocatalysts supported on indium-tin oxide.}, } @article {pmid29784823, year = {2018}, author = {Kaushik, MK and Aritake, K and Imanishi, A and Kanbayashi, T and Ichikawa, T and Shimizu, T and Urade, Y and Yanagisawa, M}, title = {Continuous intrathecal orexin delivery inhibits cataplexy in a murine model of narcolepsy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6046-6051}, pmid = {29784823}, issn = {1091-6490}, mesh = {Animals ; Brain/physiology ; Cataplexy/drug therapy/metabolism ; Disease Models, Animal ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Narcolepsy/*drug therapy ; Orexins/*administration & dosage/metabolism/*pharmacology ; Sleep/drug effects ; Sleep Disorders, Circadian Rhythm/drug therapy/metabolism ; Wakefulness/drug effects ; }, abstract = {Narcolepsy-cataplexy is a chronic neurological disorder caused by loss of orexin (hypocretin)-producing neurons, associated with excessive daytime sleepiness, sleep attacks, cataplexy, sleep paralysis, hypnagogic hallucinations, and fragmentation of nighttime sleep. Currently, human narcolepsy is treated by providing symptomatic therapies, which can be associated with an array of side effects. Although peripherally administered orexin does not efficiently penetrate the blood-brain barrier, centrally delivered orexin can effectively alleviate narcoleptic symptoms in animal models. Chronic intrathecal drug infusion through an implantable pump is a clinically available strategy to treat a number of neurological diseases. Here we demonstrate that the narcoleptic symptoms of orexin knockout mice can be reversed by lumbar-level intrathecal orexin delivery. Orexin was delivered via a chronically implanted intrathecal catheter at the upper lumbar level. The computed tomographic scan confirmed that intrathecally administered contrast agent rapidly moved from the spinal cord to the brain. Intrathecally delivered orexin was detected in the brain by radioimmunoassay at levels comparable to endogenous orexin levels. Cataplexy and sleep-onset REM sleep were significantly decreased in orexin knockout mice during and long after slow infusion of orexin (1 nmol/1 µL/h). Sleep/wake states remained unchanged both quantitatively as well as qualitatively. Intrathecal orexin failed to induce any changes in double orexin receptor-1 and -2 knockout mice. This study supports the concept of intrathecal orexin delivery as a potential therapy for narcolepsy-cataplexy to improve the well-being of patients.}, } @article {pmid29784822, year = {2018}, author = {Pukhlyakova, E and Aman, AJ and Elsayad, K and Technau, U}, title = {β-Catenin-dependent mechanotransduction dates back to the common ancestor of Cnidaria and Bilateria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6231-6236}, pmid = {29784822}, issn = {1091-6490}, mesh = {Animals ; Fetal Proteins/genetics/*metabolism ; Gastrulation/physiology ; Gene Knockdown Techniques ; Mechanotransduction, Cellular/*physiology ; Microscopy ; Myosin Type II/metabolism ; Sea Anemones/genetics/metabolism/*physiology ; T-Box Domain Proteins/genetics/*metabolism ; Up-Regulation ; beta Catenin/genetics/*metabolism ; }, abstract = {Although the genetic regulation of cellular differentiation processes is well established, recent studies have revealed the role of mechanotransduction on a variety of biological processes, including regulation of gene expression. However, it remains unclear how universal and widespread mechanotransduction is in embryonic development of animals. Here, we investigate mechanosensitive gene expression during gastrulation of the starlet sea anemone Nematostella vectensis, a cnidarian model organism. We show that the blastoporal marker gene brachyury is down-regulated by blocking myosin II-dependent gastrulation movements. Brachyury expression can be restored by applying external mechanical force. Using CRISPR/Cas9 and morpholino antisense technology, we also show that mechanotransduction leading to brachyury expression is β-catenin dependent, similar to recent findings in fish and Drosophila [Brunet T, et al. (2013) Nat Commun 4:1-15]. Finally, we demonstrate that prolonged application of mechanical stress on the embryo leads to ectopic brachyury expression. Thus, our data indicate that β-catenin-dependent mechanotransduction is an ancient gene regulatory mechanism, which was present in the common ancestor of cnidarians and bilaterians, at least 600 million years ago.}, } @article {pmid29784821, year = {2018}, author = {Tian, X and Ruan, JX and Huang, JQ and Yang, CQ and Fang, X and Chen, ZW and Hong, H and Wang, LJ and Mao, YB and Lu, S and Zhang, TZ and Chen, XY}, title = {Characterization of gossypol biosynthetic pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5410-E5418}, doi = {10.1073/pnas.1805085115}, pmid = {29784821}, issn = {1091-6490}, mesh = {Biosynthetic Pathways ; Gossypium/metabolism ; Gossypol/*biosynthesis/*metabolism ; Isomerases/biosynthesis/metabolism ; Plant Leaves/metabolism ; Sesquiterpenes/metabolism ; Transcriptome/drug effects ; }, abstract = {Gossypol and related sesquiterpene aldehydes in cotton function as defense compounds but are antinutritional in cottonseed products. By transcriptome comparison and coexpression analyses, we identified 146 candidates linked to gossypol biosynthesis. Analysis of metabolites accumulated in plants subjected to virus-induced gene silencing (VIGS) led to the identification of four enzymes and their supposed substrates. In vitro enzymatic assay and reconstitution in tobacco leaves elucidated a series of oxidative reactions of the gossypol biosynthesis pathway. The four functionally characterized enzymes, together with (+)-δ-cadinene synthase and the P450 involved in 7-hydroxy-(+)-δ-cadinene formation, convert farnesyl diphosphate (FPP) to hemigossypol, with two gaps left that each involves aromatization. Of six intermediates identified from the VIGS-treated leaves, 8-hydroxy-7-keto-δ-cadinene exerted a deleterious effect in dampening plant disease resistance if accumulated. Notably, CYP71BE79, the enzyme responsible for converting this phytotoxic intermediate, exhibited the highest catalytic activity among the five enzymes of the pathway assayed. In addition, despite their dispersed distribution in the cotton genome, all of the enzyme genes identified show a tight correlation of expression. Our data suggest that the enzymatic steps in the gossypol pathway are highly coordinated to ensure efficient substrate conversion.}, } @article {pmid29784820, year = {2018}, author = {Verma, S and Novati, G and Koumoutsakos, P}, title = {Efficient collective swimming by harnessing vortices through deep reinforcement learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5849-5854}, pmid = {29784820}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; Biomechanical Phenomena ; Computer Simulation ; Fishes/*physiology ; Learning/*physiology ; Models, Biological ; *Reinforcement (Psychology) ; Spatial Navigation/physiology ; Swimming/*physiology ; }, abstract = {Fish in schooling formations navigate complex flow fields replete with mechanical energy in the vortex wakes of their companions. Their schooling behavior has been associated with evolutionary advantages including energy savings, yet the underlying physical mechanisms remain unknown. We show that fish can improve their sustained propulsive efficiency by placing themselves in appropriate locations in the wake of other swimmers and intercepting judiciously their shed vortices. This swimming strategy leads to collective energy savings and is revealed through a combination of high-fidelity flow simulations with a deep reinforcement learning (RL) algorithm. The RL algorithm relies on a policy defined by deep, recurrent neural nets, with long-short-term memory cells, that are essential for capturing the unsteadiness of the two-way interactions between the fish and the vortical flow field. Surprisingly, we find that swimming in-line with a leader is not associated with energetic benefits for the follower. Instead, "smart swimmer(s)" place themselves at off-center positions, with respect to the axis of the leader(s) and deform their body to synchronize with the momentum of the oncoming vortices, thus enhancing their swimming efficiency at no cost to the leader(s). The results confirm that fish may harvest energy deposited in vortices and support the conjecture that swimming in formation is energetically advantageous. Moreover, this study demonstrates that deep RL can produce navigation algorithms for complex unsteady and vortical flow fields, with promising implications for energy savings in autonomous robotic swarms.}, } @article {pmid29784819, year = {2018}, author = {Gates, ZP and Vinogradov, AA and Quartararo, AJ and Bandyopadhyay, A and Choo, ZN and Evans, ED and Halloran, KH and Mijalis, AJ and Mong, SK and Simon, MD and Standley, EA and Styduhar, ED and Tasker, SZ and Touti, F and Weber, JM and Wilson, JL and Jamison, TF and Pentelute, BL}, title = {Xenoprotein engineering via synthetic libraries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5298-E5306}, doi = {10.1073/pnas.1722633115}, pmid = {29784819}, issn = {1091-6490}, support = {S10 OD016326/OD/NIH HHS/United States ; }, mesh = {Amino Acids ; Combinatorial Chemistry Techniques/*methods ; Flow Cytometry/methods ; Humans ; Microspheres ; *Peptide Library ; Protein Binding ; Protein Engineering/*methods ; Proteins/*chemical synthesis/genetics ; Tandem Mass Spectrometry/methods ; }, abstract = {Chemical methods have enabled the total synthesis of protein molecules of ever-increasing size and complexity. However, methods to engineer synthetic proteins comprising noncanonical amino acids have not kept pace, even though this capability would be a distinct advantage of the total synthesis approach to protein science. In this work, we report a platform for protein engineering based on the screening of synthetic one-bead one-compound protein libraries. Screening throughput approaching that of cell surface display was achieved by a combination of magnetic bead enrichment, flow cytometry analysis of on-bead screens, and high-throughput MS/MS-based sequencing of identified active compounds. Direct screening of a synthetic protein library by these methods resulted in the de novo discovery of mirror-image miniprotein-based binders to a ∼150-kDa protein target, a task that would be difficult or impossible by other means.}, } @article {pmid29784818, year = {2018}, author = {Tai, HC and Shen, YP and Lin, JH and Chung, DT}, title = {Acoustic evolution of old Italian violins from Amati to Stradivari.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5926-5931}, pmid = {29784818}, issn = {1091-6490}, abstract = {The shape and design of the modern violin are largely influenced by two makers from Cremona, Italy: The instrument was invented by Andrea Amati and then improved by Antonio Stradivari. Although the construction methods of Amati and Stradivari have been carefully examined, the underlying acoustic qualities which contribute to their popularity are little understood. According to Geminiani, a Baroque violinist, the ideal violin tone should "rival the most perfect human voice." To investigate whether Amati and Stradivari violins produce voice-like features, we recorded the scales of 15 antique Italian violins as well as male and female singers. The frequency response curves are similar between the Andrea Amati violin and human singers, up to ∼4.2 kHz. By linear predictive coding analyses, the first two formants of the Amati exhibit vowel-like qualities (F1/F2 = 503/1,583 Hz), mapping to the central region on the vowel diagram. Its third and fourth formants (F3/F4 = 2,602/3,731 Hz) resemble those produced by male singers. Using F1 to F4 values to estimate the corresponding vocal tract length, we observed that antique Italian violins generally resemble basses/baritones, but Stradivari violins are closer to tenors/altos. Furthermore, the vowel qualities of Stradivari violins show reduced backness and height. The unique formant properties displayed by Stradivari violins may represent the acoustic correlate of their distinctive brilliance perceived by musicians. Our data demonstrate that the pioneering designs of Cremonese violins exhibit voice-like qualities in their acoustic output.}, } @article {pmid29784817, year = {2018}, author = {Font-Clos, F and Zapperi, S and La Porta, CAM}, title = {Topography of epithelial-mesenchymal plasticity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5902-5907}, doi = {10.1073/pnas.1722609115}, pmid = {29784817}, issn = {1091-6490}, support = {291002//European Research Council/International ; }, mesh = {Cell Line, Tumor ; Databases, Genetic ; Epigenesis, Genetic/*genetics ; Epithelial-Mesenchymal Transition/*genetics ; Fractals ; Humans ; Models, Statistical ; Neoplasms/*genetics/*metabolism ; Phenotype ; }, abstract = {The transition between epithelial and mesenchymal states has fundamental importance for embryonic development, stem cell reprogramming, and cancer progression. Here, we construct a topographic map underlying epithelial-mesenchymal transitions using a combination of numerical simulations of a Boolean network model and the analysis of bulk and single-cell gene expression data. The map reveals a multitude of metastable hybrid phenotypic states, separating stable epithelial and mesenchymal states, and is reminiscent of the free energy measured in glassy materials and disordered solids. Our work not only elucidates the nature of hybrid mesenchymal/epithelial states but also provides a general strategy to construct a topographic representation of phenotypic plasticity from gene expression data using statistical physics methods.}, } @article {pmid29784816, year = {2018}, author = {An, R and Tang, Y and Chen, L and Cai, H and Lai, DH and Liu, K and Wan, L and Gong, L and Yu, L and Luo, Q and Shen, J and Lun, ZR and Ayala, FJ and Du, J}, title = {Encephalitis is mediated by ROP18 of Toxoplasma gondii, a severe pathogen in AIDS patients.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5344-E5352}, pmid = {29784816}, issn = {1091-6490}, mesh = {Acquired Immunodeficiency Syndrome/genetics/metabolism/*microbiology/pathology ; Animals ; Apoptosis/physiology ; Endoplasmic Reticulum Stress ; Female ; HIV-1/isolation & purification ; Host-Parasite Interactions ; Infectious Encephalitis/metabolism/*microbiology/pathology ; Mice ; Mice, Inbred BALB C ; Nerve Tissue Proteins/metabolism ; Phosphorylation ; Protein-Serine-Threonine Kinases/*metabolism ; Toxoplasma/*metabolism/pathogenicity ; Toxoplasmosis/genetics/metabolism/*microbiology/pathology ; }, abstract = {The neurotropic parasite Toxoplasma gondii is a globally distributed parasitic protozoan among mammalian hosts, including humans. During the course of infection, the CNS is the most commonly damaged organ among invaded tissues. The polymorphic rhoptry protein 18 (ROP18) is a key serine (Ser)/threonine (Thr) kinase that phosphorylates host proteins to modulate acute virulence. However, the basis of neurotropism and the specific substrates through which ROP18 exerts neuropathogenesis remain unknown. Using mass spectrometry, we performed proteomic analysis of proteins that selectively bind to active ROP18 and identified RTN1-C, an endoplasmic reticulum (ER) protein that is preferentially expressed in the CNS. We demonstrated that ROP18 is associated with the N-terminal portion of RTN1-C and specifically phosphorylates RTN1-C at Ser7/134 and Thr4/8/118. ROP18 phosphorylation of RTN1-C triggers ER stress-mediated apoptosis in neural cells. Remarkably, ROP18 phosphorylation of RTN1-C enhances glucose-regulated protein 78 (GRP78) acetylation by attenuating the activity of histone deacetylase (HDAC), and this event is associated with an increase of neural apoptosis. These results clearly demonstrate that both RTN1-C and HDACs are involved in T. gondii ROP18-mediated pathogenesis of encephalitis during Toxoplasma infection.}, } @article {pmid29784815, year = {2018}, author = {Casu, B and Mary, C and Sverzhinsky, A and Fouillen, A and Nanci, A and Baron, C}, title = {VirB8 homolog TraE from plasmid pKM101 forms a hexameric ring structure and interacts with the VirB6 homolog TraD.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5950-5955}, doi = {10.1073/pnas.1802501115}, pmid = {29784815}, issn = {1091-6490}, support = {P41 GM103485/GM/NIGMS NIH HHS/United States ; MOP-84239//CIHR/Canada ; MOP-110972//CIHR/Canada ; }, mesh = {Bacterial Outer Membrane Proteins/*chemistry/genetics/metabolism/ultrastructure ; Conjugation, Genetic ; Escherichia coli Proteins/*chemistry/genetics/metabolism/ultrastructure ; Membrane Proteins/*chemistry/genetics/metabolism/ultrastructure ; Plasmids/genetics ; Protein Multimerization ; Type IV Secretion Systems ; }, abstract = {Type IV secretion systems (T4SSs) are multiprotein assemblies that translocate macromolecules across the cell envelope of bacteria. X-ray crystallographic and electron microscopy (EM) analyses have increasingly provided structural information on individual T4SS components and on the entire complex. As of now, relatively little information has been available on the exact localization of the inner membrane-bound T4SS components, notably the mostly periplasmic VirB8 protein and the very hydrophobic VirB6 protein. We show here that the membrane-bound, full-length version of the VirB8 homolog TraE from the plasmid pKM101 secretion system forms a high-molecular-mass complex that is distinct from the previously characterized periplasmic portion of the protein that forms dimers. Full-length TraE was extracted from the membranes with detergents, and analysis by size-exclusion chromatography, cross-linking, and size exclusion chromatography (SEC) multiangle light scattering (MALS) shows that it forms a high-molecular-mass complex. EM and small-angle X-ray scattering (SAXS) analysis demonstrate that full-length TraE forms a hexameric complex with a central pore. We also overproduced and purified the VirB6 homolog TraD and show by cross-linking, SEC, and EM that it binds to TraE. Our results suggest that TraE and TraD interact at the substrate translocation pore of the secretion system.}, } @article {pmid29784814, year = {2018}, author = {Bang, D and Fleming, SM}, title = {Distinct encoding of decision confidence in human medial prefrontal cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6082-6087}, pmid = {29784814}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 203147/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Brain/physiology ; Brain Mapping/methods ; Choice Behavior/*physiology ; Decision Making/*physiology ; Female ; Gyrus Cinguli/physiology ; Humans ; Magnetic Resonance Imaging/methods ; Male ; Prefrontal Cortex/*physiology ; Reproducibility of Results ; }, abstract = {Our confidence in a choice and the evidence pertaining to a choice appear to be inseparable. However, an emerging computational consensus holds that the brain should maintain separate estimates of these quantities for adaptive behavioral control. We have devised a psychophysical task to decouple confidence in a perceptual decision from both the reliability of sensory evidence and the relation of such evidence with respect to a choice boundary. Using human fMRI, we found that an area in the medial prefrontal cortex, the perigenual anterior cingulate cortex (pgACC), tracked expected performance, an aggregate signature of decision confidence, whereas neural areas previously proposed to encode decision confidence instead tracked sensory reliability (posterior parietal cortex and ventral striatum) or boundary distance (presupplementary motor area). Supporting that information encoded by pgACC is central to a subjective sense of decision confidence, we show that pgACC activity does not simply covary with expected performance, but is also linked to within-subject and between-subject variation in explicit confidence estimates. Our study is consistent with the proposal that the brain maintains choice-dependent and choice-independent estimates of certainty, and sheds light on why dysfunctional confidence often emerges following prefrontal lesions and/or degeneration.}, } @article {pmid29784813, year = {2018}, author = {Lee, M and Kim, JH and Yoon, I and Lee, C and Fallahi Sichani, M and Kang, JS and Kang, J and Guo, M and Lee, KY and Han, G and Kim, S and Han, JM}, title = {Coordination of the leucine-sensing Rag GTPase cycle by leucyl-tRNA synthetase in the mTORC1 signaling pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5279-E5288}, doi = {10.1073/pnas.1801287115}, pmid = {29784813}, issn = {1091-6490}, mesh = {Cell Line/metabolism ; GTP Phosphohydrolases/metabolism ; Humans ; Leucine/metabolism ; Leucine-tRNA Ligase/*metabolism ; Lysosomes/metabolism ; Mechanistic Target of Rapamycin Complex 1/*metabolism ; Monomeric GTP-Binding Proteins/*metabolism ; Multiprotein Complexes/metabolism ; Nuclear Proteins/metabolism ; Protein Binding ; Protein Biosynthesis ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {A protein synthesis enzyme, leucyl-tRNA synthetase (LRS), serves as a leucine sensor for the mechanistic target of rapamycin complex 1 (mTORC1), which is a central effector for protein synthesis, metabolism, autophagy, and cell growth. However, its significance in mTORC1 signaling and cancer growth and its functional relationship with other suggested leucine signal mediators are not well-understood. Here we show the kinetics of the Rag GTPase cycle during leucine signaling and that LRS serves as an initiating "ON" switch via GTP hydrolysis of RagD that drives the entire Rag GTPase cycle, whereas Sestrin2 functions as an "OFF" switch by controlling GTP hydrolysis of RagB in the Rag GTPase-mTORC1 axis. The LRS-RagD axis showed a positive correlation with mTORC1 activity in cancer tissues and cells. The GTP-GDP cycle of the RagD-RagB pair, rather than the RagC-RagA pair, is critical for leucine-induced mTORC1 activation. The active RagD-RagB pair can overcome the absence of the RagC-RagA pair, but the opposite is not the case. This work suggests that the GTPase cycle of RagD-RagB coordinated by LRS and Sestrin2 is critical for controlling mTORC1 activation, and thus will extend the current understanding of the amino acid-sensing mechanism.}, } @article {pmid29784812, year = {2018}, author = {Granados, AA and Pietsch, JMJ and Cepeda-Humerez, SA and Farquhar, IL and Tkačik, G and Swain, PS}, title = {Distributed and dynamic intracellular organization of extracellular information.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6088-6093}, pmid = {29784812}, issn = {1091-6490}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Cell Nucleus/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Cytoplasm/metabolism ; DNA-Binding Proteins/metabolism ; Environment ; Extracellular Space/physiology ; Gene Expression Regulation, Fungal/genetics ; *Gene-Environment Interaction ; Intracellular Signaling Peptides and Proteins/*physiology ; Mitogen-Activated Protein Kinases/metabolism ; Models, Biological ; Protein Transport ; Saccharomyces cerevisiae/metabolism ; Saccharomyces cerevisiae Proteins/metabolism ; Saccharomycetales/metabolism ; Signal Transduction ; Stress, Physiological ; Transcription Factors/*metabolism/physiology ; }, abstract = {Although cells respond specifically to environments, how environmental identity is encoded intracellularly is not understood. Here, we study this organization of information in budding yeast by estimating the mutual information between environmental transitions and the dynamics of nuclear translocation for 10 transcription factors. Our method of estimation is general, scalable, and based on decoding from single cells. The dynamics of the transcription factors are necessary to encode the highest amounts of extracellular information, and we show that information is transduced through two channels: Generalists (Msn2/4, Tod6 and Dot6, Maf1, and Sfp1) can encode the nature of multiple stresses, but only if stress is high; specialists (Hog1, Yap1, and Mig1/2) encode one particular stress, but do so more quickly and for a wider range of magnitudes. In particular, Dot6 encodes almost as much information as Msn2, the master regulator of the environmental stress response. Each transcription factor reports differently, and it is only their collective behavior that distinguishes between multiple environmental states. Changes in the dynamics of the localization of transcription factors thus constitute a precise, distributed internal representation of extracellular change. We predict that such multidimensional representations are common in cellular decision-making.}, } @article {pmid29784811, year = {2018}, author = {Shmakov, SA and Makarova, KS and Wolf, YI and Severinov, KV and Koonin, EV}, title = {Systematic prediction of genes functionally linked to CRISPR-Cas systems by gene neighborhood analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5307-E5316}, pmid = {29784811}, issn = {1091-6490}, mesh = {Archaea/genetics ; Bacteria/genetics ; Base Sequence ; CRISPR-Associated Proteins/genetics ; CRISPR-Cas Systems/*genetics ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; Computer Simulation ; Evolution, Molecular ; Genes, Bacterial ; Genetic Testing ; Genome, Archaeal ; Genome, Bacterial ; Phylogeny ; }, abstract = {The CRISPR-Cas systems of bacterial and archaeal adaptive immunity consist of direct repeat arrays separated by unique spacers and multiple CRISPR-associated (cas) genes encoding proteins that mediate all stages of the CRISPR response. In addition to the relatively small set of core cas genes that are typically present in all CRISPR-Cas systems of a given (sub)type and are essential for the defense function, numerous genes occur in CRISPR-cas loci only sporadically. Some of these have been shown to perform various ancillary roles in CRISPR response, but the functional relevance of most remains unknown. We developed a computational strategy for systematically detecting genes that are likely to be functionally linked to CRISPR-Cas. The approach is based on a "CRISPRicity" metric that measures the strength of CRISPR association for all protein-coding genes from sequenced bacterial and archaeal genomes. Uncharacterized genes with CRISPRicity values comparable to those of cas genes are considered candidate CRISPR-linked genes. We describe additional criteria to predict functionally relevance for genes in the candidate set and identify 79 genes as strong candidates for functional association with CRISPR-Cas systems. A substantial majority of these CRISPR-linked genes reside in type III CRISPR-cas loci, which implies exceptional functional versatility of type III systems. Numerous candidate CRISPR-linked genes encode integral membrane proteins suggestive of tight membrane association of CRISPR-Cas systems, whereas many others encode proteins implicated in various signal transduction pathways. These predictions provide ample material for improving annotation of CRISPR-cas loci and experimental characterization of previously unsuspected aspects of CRISPR-Cas system functionality.}, } @article {pmid29784810, year = {2018}, author = {McHill, AW and Hull, JT and Wang, W and Czeisler, CA and Klerman, EB}, title = {Chronic sleep curtailment, even without extended (>16-h) wakefulness, degrades human vigilance performance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6070-6075}, pmid = {29784810}, issn = {1091-6490}, support = {R01 HL128538/HL/NHLBI NIH HHS/United States ; KL2 TR002370/TR/NCATS NIH HHS/United States ; K24 HL105664/HL/NHLBI NIH HHS/United States ; F32 DK107146/DK/NIDDK NIH HHS/United States ; T32 HL007901/HL/NHLBI NIH HHS/United States ; R01 HL114088/HL/NHLBI NIH HHS/United States ; P01 AG009975/AG/NIA NIH HHS/United States ; R01 GM105018/GM/NIGMS NIH HHS/United States ; R21 HD086392/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Arousal ; Attention ; Circadian Rhythm/physiology ; Cognition ; Female ; Healthy Volunteers ; Humans ; Male ; Polysomnography ; Psychomotor Performance ; Reaction Time ; Self Report ; Sleep/*physiology ; Sleep Deprivation/*physiopathology ; Sleep Wake Disorders/physiopathology ; Time Factors ; Wakefulness/*physiology ; }, abstract = {Millions of individuals routinely remain awake for more than 18 h daily, which causes performance decrements. It is unknown if these functional impairments are the result of that extended wakefulness or from the associated shortened sleep durations. We therefore examined changes in objective reaction time performance and subjective alertness in a 32-d inpatient protocol in which participants were scheduled to wakefulness durations below 16 h while on a 20-h "day," with randomization into standard sleep:wake ratio (1:2) or chronic sleep restriction (CSR) ratio (1:3.3) conditions. This protocol allowed determination of the contribution of sleep deficiency independent of extended wakefulness, since individual episodes of wakefulness in the CSR condition were only 15.33 h in duration (less than the usual 16 h of wakefulness in a 24-h day) and sleep episodes were 4.67 h in duration each cycle. We found that chronic short sleep duration, even without extended wakefulness, doubled neurobehavioral reaction time performance and increased lapses of attention fivefold, yet did not uniformly decrease self-reported alertness. Further, these impairments in neurobehavioral performance were worsened during the circadian night and were not recovered during the circadian day, indicating that the deleterious effect from the homeostatic buildup of CSR is expressed even during the circadian promotion of daytime arousal. These findings reveal a fundamental aspect of human biology: Chronic insufficient sleep duration equivalent to 5.6 h of sleep opportunity per 24 h impairs neurobehavioral performance and self-assessment of alertness, even without extended wakefulness.}, } @article {pmid29784809, year = {2018}, author = {}, title = {Correction for Vaidyanathan, Core Concept: Microgrids offer flexible energy generation, for a price.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5250}, doi = {10.1073/pnas.1807693115}, pmid = {29784809}, issn = {1091-6490}, } @article {pmid29784808, year = {2018}, author = {Volovelsky, O and Nguyen, T and Jarmas, AE and Combes, AN and Wilson, SB and Little, MH and Witte, DP and Brunskill, EW and Kopan, R}, title = {Hamartin regulates cessation of mouse nephrogenesis independently of Mtor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5998-6003}, pmid = {29784808}, issn = {1091-6490}, support = {R01 DK106225/DK/NIDDK NIH HHS/United States ; UH3 DK107344/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Female ; Male ; Mice ; Mice, Transgenic ; *Nephrons/chemistry/cytology/growth & development/physiology ; Organogenesis/*physiology ; TOR Serine-Threonine Kinases/genetics/*metabolism ; Tuberous Sclerosis Complex 1 Protein ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {Nephrogenesis concludes by the 36th week of gestation in humans and by the third day of postnatal life in mice. Extending the nephrogenic period may reduce the onset of adult renal and cardiovascular disease associated with low nephron numbers. We conditionally deleted either Mtor or Tsc1 (coding for hamartin, an inhibitor of Mtor) in renal progenitor cells. Loss of one Mtor allele caused a reduction in nephron numbers; complete deletion led to severe paucity of glomeruli in the kidney resulting in early death after birth. By contrast, loss of one Tsc1 allele from renal progenitors resulted in a 25% increase in nephron endowment with no adverse effects. Increased progenitor engraftment rates ex vivo relative to controls correlated with prolonged nephrogenesis through the fourth postnatal day. Complete loss of both Tsc1 alleles in renal progenitors led to a lethal tubular lesion. The hamartin phenotypes are not dependent on the inhibitory effect of TSC on the Mtor complex but are dependent on Raptor.}, } @article {pmid29784807, year = {2018}, author = {Guo, J and Zhang, T and Guo, Y and Sun, T and Li, H and Zhang, X and Yin, H and Cao, G and Yin, Y and Wang, H and Shi, L and Guo, X and Sha, J and Eppig, JJ and Su, YQ}, title = {Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5326-E5333}, pmid = {29784807}, issn = {1091-6490}, mesh = {Animals ; Cell Differentiation/physiology ; Cells, Cultured ; Female ; Follicle Stimulating Hormone/blood ; Granulosa Cells/*cytology/enzymology/metabolism ; Infertility, Female/genetics/metabolism/pathology ; Meiosis/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oocytes/*cytology/enzymology/metabolism ; Oogenesis ; Ovarian Follicle/cytology/enzymology/metabolism ; TOR Serine-Threonine Kinases/genetics/*metabolism ; }, abstract = {MTOR (mechanistic target of rapamycin) is a widely recognized integrator of signals and pathways key for cellular metabolism, proliferation, and differentiation. Here we show that conditional knockout (cKO) of Mtor in either primordial or growing oocytes caused infertility but differentially affected oocyte quality, granulosa cell fate, and follicular development. cKO of Mtor in nongrowing primordial oocytes caused defective follicular development leading to progressive degeneration of oocytes and loss of granulosa cell identity coincident with the acquisition of immature Sertoli cell-like characteristics. Although Mtor was deleted at the primordial oocyte stage, DNA damage accumulated in oocytes during their later growth, and there was a marked alteration of the transcriptome in the few oocytes that achieved the fully grown stage. Although oocyte quality and fertility were also compromised when Mtor was deleted after oocytes had begun to grow, these occurred without overtly affecting folliculogenesis or the oocyte transcriptome. Nevertheless, there was a significant change in a cohort of proteins in mature oocytes. In particular, down-regulation of PRC1 (protein regulator of cytokinesis 1) impaired completion of the first meiotic division. Therefore, MTOR-dependent pathways in primordial or growing oocytes differentially affected downstream processes including follicular development, sex-specific identity of early granulosa cells, maintenance of oocyte genome integrity, oocyte gene expression, meiosis, and preimplantation developmental competence.}, } @article {pmid29784806, year = {2018}, author = {Bonelli, N and Montis, C and Mirabile, A and Berti, D and Baglioni, P}, title = {Restoration of paper artworks with microemulsions confined in hydrogels for safe and efficient removal of adhesive tapes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5932-5937}, pmid = {29784806}, issn = {1091-6490}, abstract = {The presence of pressure-sensitive tapes (PSTs) on paper artworks, either fortuitous or specifically applied for conservation purposes, is one of the most frequent and difficult issues encountered during restoration. Aged PSTs can damage or disfigure artworks, compromising structural integrity, readability, and enjoyment. Current procedures are often inherently hazardous for artistic media and paper support. Challenged by the necessity to remove PSTs from a contemporary and an ancient drawing (20th century, by artists da Silva and Hayter, and a 16th-century drawing of one figure from the Sistine Chapel by Michelangelo), we addressed this issue from a physicochemical perspective, leveraging colloid and interface science. After a characterization of the specific PSTs present on the artifact, we selected a highly water-retentive hydrogel as the host of 23% wt/wt of "green" organic solvents uniformly dispersed within the gel in the form of nanosized droplets. The double confinement of the organic solvent in the nanodroplets and into the gel network promotes a tailored, controlled removal of PSTs of different natures, with virtually no interaction with the solvent-sensitive artwork. This noninvasive procedure allows complete retrieval of artwork readability. For instance, in the ancient drawing, the PST totally concealed the inscription, "di mano di Michelangelo" ("from Michelangelo's hand"), a possibly false attribution hidden by a collector, which is now perfectly visible and whose origin is currently under investigation. Remarkably, the same methodology was successful for the removal of aged PST adhesive penetrated inside paper fibers of a drawing from the celebrated artist Lucio Fontana.}, } @article {pmid29784805, year = {2018}, author = {Holst, MK and Heinemeier, J and Hertz, E and Jensen, P and Løvschal, M and Mollerup, L and Odgaard, BV and Olsen, J and Søe, NE and Kristiansen, SM}, title = {Direct evidence of a large Northern European Roman period martial event and postbattle corpse manipulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5920-5925}, pmid = {29784805}, issn = {1091-6490}, mesh = {Adult ; Archaeology ; Armed Conflicts/*history ; Bone and Bones/*pathology ; Burial/*history ; Cadaver ; *Ceremonial Behavior ; Denmark ; Female ; History, Ancient ; Humans ; Male ; Middle Aged ; Radiometric Dating ; Roman World/history ; Young Adult ; }, abstract = {New archaeological excavations at Alken Enge, Jutland, Denmark, have revealed a comprehensive assemblage of disarticulated human remains within a 75-ha wetland area. A minimum of 82 individuals have been uncovered. Based on the distribution, the total population is estimated to be greater than 380 individuals, exclusively male and predominantly adult. The chronological radiocarbon evidence of the human bones indicates that they belong to a single, large event in the early first century AD. The bones show a high frequency of unhealed trauma from sharp-edged weapons, which, together with finds of military equipment, suggests that the find is of martial character. Taphonomic traces indicate that the bones were exposed to animal gnawing for a period of between 6 mo and 1 y before being deposited in the lake. Furthermore, the find situations, including collections of bones, ossa coxae threaded onto a stick, and cuts and scraping marks, provide evidence of the systematic treatment of the human corpses after the time of exposure. The finds are interpreted as the remains of an organized and possibly ritually embedded clearing of a battlefield, including the physical manipulation of the partly skeletonized bones of the deceased fighters and subsequent deposition in the lake. The date places the finds in the context of the Germanic region at the peak of the Roman expansion northward and provides the earliest direct archaeological evidence of large-scale conflict among the Germanic populations and a demonstration of hitherto unrecognized postbattle practices.}, } @article {pmid29784804, year = {2018}, author = {Culbertson, AT and Ehrlich, JJ and Choe, JY and Honzatko, RB and Zabotina, OA}, title = {Structure of xyloglucan xylosyltransferase 1 reveals simple steric rules that define biological patterns of xyloglucan polymers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6064-6069}, pmid = {29784804}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/*metabolism/*ultrastructure ; Cell Wall/metabolism ; Crystallography, X-Ray/methods ; Glucans/genetics/metabolism ; Models, Biological ; Pentosyltransferases/genetics/*metabolism/*ultrastructure ; Xylans/genetics/metabolism ; }, abstract = {The plant cell wall is primarily a polysaccharide mesh of the most abundant biopolymers on earth. Although one of the richest sources of biorenewable materials, the biosynthesis of the plant polysaccharides is poorly understood. Structures of many essential plant glycosyltransferases are unknown and suitable substrates are often unavailable for in vitro analysis. The dearth of such information impedes the development of plants better suited for industrial applications. Presented here are structures of Arabidopsis xyloglucan xylosyltransferase 1 (XXT1) without ligands and in complexes with UDP and cellohexaose. XXT1 initiates side-chain extensions from a linear glucan polymer by transferring the xylosyl group from UDP-xylose during xyloglucan biosynthesis. XXT1, a homodimer and member of the GT-A fold family of glycosyltransferases, binds UDP analogously to other GT-A fold enzymes. Structures here and the properties of mutant XXT1s are consistent with a SNi-like catalytic mechanism. Distinct from other systems is the recognition of cellohexaose by way of an extended cleft. The XXT1 dimer alone cannot produce xylosylation patterns observed for native xyloglucans because of steric constraints imposed by the acceptor binding cleft. Homology modeling of XXT2 and XXT5, the other two xylosyltransferases involved in xyloglucan biosynthesis, reveals a structurally altered cleft in XXT5 that could accommodate a partially xylosylated glucan chain produced by XXT1 and/or XXT2. An assembly of the three XXTs can produce the xylosylation patterns of native xyloglucans, suggesting the involvement of an organized multienzyme complex in the xyloglucan biosynthesis.}, } @article {pmid29784803, year = {2018}, author = {}, title = {Correction for DeMille et al., Worldwide distribution of the DCDC2 READ1 regulatory element and its relationship with phoneme variation across languages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5251}, doi = {10.1073/pnas.1807672115}, pmid = {29784803}, issn = {1091-6490}, } @article {pmid29784802, year = {2018}, author = {Morgan Chan, Z and Kitchaev, DA and Nelson Weker, J and Schnedermann, C and Lim, K and Ceder, G and Tumas, W and Toney, MF and Nocera, DG}, title = {Electrochemical trapping of metastable Mn3+ ions for activation of MnO2 oxygen evolution catalysts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5261-E5268}, pmid = {29784802}, issn = {1091-6490}, abstract = {Electrodeposited manganese oxide films are promising catalysts for promoting the oxygen evolution reaction (OER), especially in acidic solutions. The activity of these catalysts is known to be enhanced by the introduction of Mn3+ We present in situ electrochemical and X-ray absorption spectroscopic studies, which reveal that Mn3+ may be introduced into MnO2 by an electrochemically induced comproportionation reaction with Mn2+ and that Mn3+ persists in OER active films. Extended X-ray absorption fine structure (EXAFS) spectra of the Mn3+-activated films indicate a decrease in the Mn-O coordination number, and Raman microspectroscopy reveals the presence of distorted Mn-O environments. Computational studies show that Mn3+ is kinetically trapped in tetrahedral sites and in a fully oxidized structure, consistent with the reduction of coordination number observed in EXAFS. Although in a reduced state, computation shows that Mn3+ states are stabilized relative to those of oxygen and that the highest occupied molecular orbital (HOMO) is thus dominated by oxygen states. Furthermore, the Mn3+(Td) induces local strain on the oxide sublattice as observed in Raman spectra and results in a reduced gap between the HOMO and the lowest unoccupied molecular orbital (LUMO). The confluence of a reduced HOMO-LUMO gap and oxygen-based HOMO results in the facilitation of OER on the application of anodic potentials to the δ-MnO2 polymorph incorporating Mn3+ ions.}, } @article {pmid29784801, year = {2018}, author = {Shi, X and Wu, Y and Rao, CR}, title = {Consistent and powerful non-Euclidean graph-based change-point test with applications to segmenting random interfered video data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5914-5919}, doi = {10.1073/pnas.1804649115}, pmid = {29784801}, issn = {1091-6490}, abstract = {The change-point detection has been carried out in terms of the Euclidean minimum spanning tree (MST) and shortest Hamiltonian path (SHP), with successful applications in the determination of authorship of a classic novel, the detection of change in a network over time, the detection of cell divisions, etc. However, these Euclidean graph-based tests may fail if a dataset contains random interferences. To solve this problem, we present a powerful non-Euclidean SHP-based test, which is consistent and distribution-free. The simulation shows that the test is more powerful than both Euclidean MST- and SHP-based tests and the non-Euclidean MST-based test. Its applicability in detecting both landing and departure times in video data of bees' flower visits is illustrated.}, } @article {pmid29784800, year = {2018}, author = {Park, J and Lim, CJ and Shen, M and Park, HJ and Cha, JY and Iniesto, E and Rubio, V and Mengiste, T and Zhu, JK and Bressan, RA and Lee, SY and Lee, BH and Jin, JB and Pardo, JM and Kim, WY and Yun, DJ}, title = {Epigenetic switch from repressive to permissive chromatin in response to cold stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5400-E5409}, pmid = {29784800}, issn = {1091-6490}, mesh = {Acetylation ; Arabidopsis/genetics/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Chromatin/*metabolism/*physiology ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; Cold Temperature ; Cold-Shock Response/genetics/physiology ; Epigenesis, Genetic/genetics ; Epigenomics/methods ; Gene Expression Regulation, Plant/genetics ; Histone Deacetylases/genetics/metabolism ; Histones/metabolism ; Promoter Regions, Genetic/genetics ; Protein Processing, Post-Translational ; Transcription Factors/metabolism ; }, abstract = {Switching from repressed to active status in chromatin regulation is part of the critical responses that plants deploy to survive in an ever-changing environment. We previously reported that HOS15, a WD40-repeat protein, is involved in histone deacetylation and cold tolerance in Arabidopsis However, it remained unknown how HOS15 regulates cold responsive genes to affect cold tolerance. Here, we show that HOS15 interacts with histone deacetylase 2C (HD2C) and both proteins together associate with the promoters of cold-responsive COR genes, COR15A and COR47 Cold induced HD2C degradation is mediated by the CULLIN4 (CUL4)-based E3 ubiquitin ligase complex in which HOS15 acts as a substrate receptor. Interference with the association of HD2C and the COR gene promoters by HOS15 correlates with increased acetylation levels of histone H3. HOS15 also interacts with CBF transcription factors to modulate cold-induced binding to the COR gene promoters. Our results here demonstrate that cold induces HOS15-mediated chromatin modifications by degrading HD2C. This switches the chromatin structure status and facilitates recruitment of CBFs to the COR gene promoters. This is an apparent requirement to acquire cold tolerance.}, } @article {pmid29784799, year = {2018}, author = {Lee, SK and Kim, YH and Chow, P and Xiao, Y and Ji, C and Shen, G}, title = {Amorphous boron oxide at megabar pressures via inelastic X-ray scattering.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5855-5860}, doi = {10.1073/pnas.1800777115}, pmid = {29784799}, issn = {1091-6490}, abstract = {Structural transition in amorphous oxides, including glasses, under extreme compression above megabar pressures (>1 million atmospheric pressure, 100 GPa) results in unique densification paths that differ from those in crystals. Experimentally verifying the atomistic origins of such densifications beyond 100 GPa remains unknown. Progress in inelastic X-ray scattering (IXS) provided insights into the pressure-induced bonding changes in oxide glasses; however, IXS has a signal intensity several orders of magnitude smaller than that of elastic X-rays, posing challenges for probing glass structures above 100 GPa near the Earth's core-mantle boundary. Here, we report megabar IXS spectra for prototypical B2O3 glasses at high pressure up to ∼120 GPa, where it is found that only four-coordinated boron ([4]B) is prevalent. The reduction in the [4]B-O length up to 120 GPa is minor, indicating the extended stability of sp3-bonded [4]B. In contrast, a substantial decrease in the average O-O distance upon compression is revealed, suggesting that the densification in B2O3 glasses is primarily due to O-O distance reduction without the formation of [5]B. Together with earlier results with other archetypal oxide glasses, such as SiO2 and GeO2, the current results confirm that the transition pressure of the formation of highly coordinated framework cations systematically increases with the decreasing atomic radius of the cations. These observations highlight a new opportunity to study the structure of oxide glass above megabar pressures, yielding the atomistic origins of densification in melts at the Earth's core-mantle boundary.}, } @article {pmid29784798, year = {2018}, author = {Tzeng, SY and McHugh, KJ and Behrens, AM and Rose, S and Sugarman, JL and Ferber, S and Langer, R and Jaklenec, A}, title = {Stabilized single-injection inactivated polio vaccine elicits a strong neutralizing immune response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5269-E5278}, pmid = {29784798}, issn = {1091-6490}, mesh = {Animals ; Disease Models, Animal ; Female ; Humans ; *Immunization Schedule ; Injections/methods ; Microspheres ; Poliomyelitis/prevention & control ; Poliovirus Vaccine, Inactivated/*administration & dosage ; Rats ; Rats, Wistar ; Vaccination/*methods ; }, abstract = {Vaccination in the developing world is hampered by limited patient access, which prevents individuals from receiving the multiple injections necessary for protective immunity. Here, we developed an injectable microparticle formulation of the inactivated polio vaccine (IPV) that releases multiple pulses of stable antigen over time. To accomplish this, we established an IPV stabilization strategy using cationic polymers for pH modulation to enhance traditional small-molecule-based stabilization methods. We investigated the mechanism of this strategy and showed that it was broadly applicable to all three antigens in IPV. Our lead formulations released two bursts of IPV 1 month apart, mimicking a typical vaccination schedule in the developing world. One injection of the controlled-release formulations elicited a similar or better neutralizing response in rats, considered the correlate of protection in humans, than multiple injections of liquid vaccine. This single-administration vaccine strategy has the potential to improve vaccine coverage in the developing world.}, } @article {pmid29784797, year = {2018}, author = {Miao, C and Xiao, L and Hua, K and Zou, C and Zhao, Y and Bressan, RA and Zhu, JK}, title = {Mutations in a subfamily of abscisic acid receptor genes promote rice growth and productivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6058-6063}, doi = {10.1073/pnas.1804774115}, pmid = {29784797}, issn = {1091-6490}, mesh = {Abscisic Acid/*metabolism ; Arabidopsis/genetics ; Arabidopsis Proteins/*genetics ; Carrier Proteins/metabolism ; Gene Expression Regulation, Plant/genetics ; Germination/genetics ; Intracellular Signaling Peptides and Proteins/*genetics ; Membrane Transport Proteins/metabolism ; Mutation ; Oryza/genetics ; Plant Growth Regulators/metabolism ; Signal Transduction ; }, abstract = {Abscisic acid (ABA) is a key phytohormone that controls plant growth and stress responses. It is sensed by the pyrabactin resistance 1 (PYR1)/PYR1-like (PYL)/regulatory components of the ABA receptor (RCAR) family of proteins. Here, we utilized CRISPR/Cas9 technology to edit group I (PYL1-PYL6 and PYL12) and group II (PYL7-PYL11 and PYL13) PYL genes in rice. Characterization of the combinatorial mutants suggested that genes in group I have more important roles in stomatal movement, seed dormancy, and growth regulation than those in group II. Among all of the single pyl mutants, only pyl1 and pyl12 exhibited significant defects in seed dormancy. Interestingly, high-order group I mutants, but not any group II mutants, displayed enhanced growth. Among group I mutants, pyl1/4/6 exhibited the best growth and improved grain productivity in natural paddy field conditions, while maintaining nearly normal seed dormancy. Our results suggest that a subfamily of rice PYLs has evolved to have particularly important roles in regulating plant growth and reveal a genetic strategy to improve rice productivity.}, } @article {pmid29784796, year = {2018}, author = {Srivastava, G and Mehrotra, RC and Dilcher, DL}, title = {Paleocene Ipomoea (Convolvulaceae) from India with implications for an East Gondwana origin of Convolvulaceae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6028-6033}, pmid = {29784796}, issn = {1091-6490}, mesh = {Convolvulaceae/*cytology ; Evolution, Molecular ; Fossils ; India ; Ipomoea/*cytology ; Phylogeny ; Phylogeography/methods ; Plant Leaves/cytology/metabolism ; Solanaceae/cytology ; }, abstract = {The morning glory family, Convolvulaceae, is globally important in medicine and food crops. The family has worldwide distribution in a variety of habitats; however, its fossil record is very poorly documented. The current fossil record suggests an origin in North America, which is in contrast to molecular data that indicate an East Gondwana origin. We report Ipomoea leaves from the late Paleocene (Thanetian; 58.7-55.8 million years ago) of India, which was a part of East Gondwana during this time. This is the earliest fossil record for both the family Convolvulaceae and the order Solanales. This suggests that the sister families Convolvulaceae and Solanaceae diverged before the Eocene in Gondwana-derived continents. The evidence presented here supports the conclusion from molecular phylogenetic analysis of an East Gondwana origin of Convolvulaceae.}, } @article {pmid29784795, year = {2018}, author = {}, title = {Correction for Woo et al., Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5253}, doi = {10.1073/pnas.1807631115}, pmid = {29784795}, issn = {1091-6490}, } @article {pmid29784794, year = {2018}, author = {Xiao, H and Shin, H and Goddard, WA}, title = {Synergy between Fe and Ni in the optimal performance of (Ni,Fe)OOH catalysts for the oxygen evolution reaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5872-5877}, pmid = {29784794}, issn = {1091-6490}, abstract = {The oxygen evolution reaction (OER) is critical to solar production of fuels, but the reaction mechanism underlying the performance for a best OER catalyst, Fe-doped NiOOH [(Ni,Fe)OOH], remains highly controversial. We used grand canonical quantum mechanics to predict the OER mechanisms including kinetics and thus overpotentials as a function of Fe content in (Ni,Fe)OOH catalysts. We find that density functional theory (DFT) without exact exchange predicts that addition of Fe does not reduce the overpotential much. However, DFT with exact exchange predicts dramatic improvement in performance for (Ni,Fe)OOH, leading to an overpotential of 0.42 V and a Tafel slope of 23 mV/decade (dec), in good agreement with experiments, 0.3-0.4 V and 30 mV/dec. We reveal that the high spin [Formula: see text] Fe(IV) leads to efficient formation of an active O radical intermediate, while the closed shell [Formula: see text] Ni(IV) catalyzes the subsequent O-O coupling, and thus it is the synergy between Fe and Ni that delivers the optimal performance for OER.}, } @article {pmid29784793, year = {2018}, author = {Yoon, YS and Tsai, WW and Van de Velde, S and Chen, Z and Lee, KF and Morgan, DA and Rahmouni, K and Matsumura, S and Wiater, E and Song, Y and Montminy, M}, title = {cAMP-inducible coactivator CRTC3 attenuates brown adipose tissue thermogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5289-E5297}, pmid = {29784793}, issn = {1091-6490}, support = {R01 DK083834/DK/NIDDK NIH HHS/United States ; R24 OD023076/OD/NIH HHS/United States ; P01 HL084207/HL/NHLBI NIH HHS/United States ; U19 MH114831/MH/NIMH NIH HHS/United States ; RF1 AG047669/AG/NIA NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {Adipocytes, Brown/metabolism ; Adipose Tissue, Brown/*metabolism ; Adiposity/genetics/physiology ; Animals ; Cell Differentiation/physiology ; Cyclic AMP Response Element-Binding Protein/metabolism ; Energy Metabolism ; Mice ; Mice, Knockout ; MicroRNAs/genetics ; Signal Transduction ; Sympathetic Nervous System/metabolism ; Thermogenesis/*physiology ; Transcription Factors/genetics/*metabolism ; }, abstract = {In response to cold exposure, placental mammals maintain body temperature by increasing sympathetic nerve activity in brown adipose tissue (BAT). Triggering of β-adrenergic receptors on brown adipocytes stimulates thermogenesis via induction of the cAMP/PKA pathway. Although cAMP response element-binding protein (CREB) and its coactivators-the cAMP-regulated transcriptional coactivators (CRTCs)-mediate transcriptional effects of cAMP in most tissues, other transcription factors such as ATF2 appear critical for induction of thermogenic genes by cAMP in BAT. Brown adipocytes arise from Myf5-positive mesenchymal cells under the control of PRDM16, a coactivator that concurrently represses differentiation along the skeletal muscle lineage. Here, we show that the CREB coactivator CRTC3 is part of an inhibitory feedback pathway that antagonizes PRDM16-dependent differentiation. Mice with a knockout of CRTC3 in BAT (BKO) have increased cold tolerance and reduced adiposity, whereas mice overexpressing constitutively active CRTC3 in adipose tissue are more cold sensitive and have greater fat mass. CRTC3 reduced sympathetic nerve activity in BAT by up-regulating the expression of miR-206, a microRNA that promotes differentiation along the myogenic lineage and that we show here decreases the expression of VEGFA and neurotrophins critical for BAT innervation and vascularization. Sympathetic nerve activity to BAT was enhanced in BKO mice, leading to increases in catecholamine signaling that stimulated energy expenditure. As reexpression of miR-206 in BAT from BKO mice reversed the salutary effects of CRTC3 depletion on cold tolerance, our studies suggest that small-molecule inhibitors against this coactivator may provide therapeutic benefit to overweight individuals.}, } @article {pmid29784792, year = {2018}, author = {Bartlett, R and Elrick, M and Wheeley, JR and Polyak, V and Desrochers, A and Asmerom, Y}, title = {Abrupt global-ocean anoxia during the Late Ordovician-early Silurian detected using uranium isotopes of marine carbonates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5896-5901}, doi = {10.1073/pnas.1802438115}, pmid = {29784792}, issn = {1091-6490}, abstract = {Widespread marine anoxia is hypothesized as the trigger for the second pulse of the Late Ordovician (Hirnantian) mass extinction based on lithologic and geochemical proxies that record local bottom waters or porewaters. We test the anoxia hypothesis using δ238U values of marine limestones as a global seawater redox proxy. The δ238U trends at Anticosti Island, Canada, document an abrupt late Hirnantian ∼0.3‰ negative shift continuing through the early Silurian indicating more reducing seawater conditions. The lack of observed anoxic facies and no covariance among δ238U values and other local redox proxies suggests that the δ238U trends represent a global-ocean redox record. The Hirnantian ocean anoxic event (HOAE) onset is coincident with the extinction pulse indicating its importance in triggering it. Anoxia initiated during high sea levels before peak Hirnantian glaciation, and continued into the subsequent lowstand and early Silurian deglacial eustatic rise, implying that major climatic and eustatic changes had little effect on global-ocean redox conditions. The HOAE occurred during a global δ13C positive excursion, but lasted longer indicating that controls on the C budget were partially decoupled from global-ocean redox trends. U cycle modeling suggests that there was a ∼15% increase in anoxic seafloor area and ∼80% of seawater U was sequestered into anoxic sediments during the HOAE. Unlike other ocean anoxic events (OAE), the HOAE occurred during peak and waning icehouse conditions rather than during greenhouse climates. We interpret that anoxia was driven by global cooling, which reorganized thermohaline circulation, decreased deep-ocean ventilation, enhanced nutrient fluxes, stimulated productivity, which lead to expanded oxygen minimum zones.}, } @article {pmid29784791, year = {2018}, author = {Lee, GJ and Han, G and Yun, HM and Lim, JJ and Noh, S and Lee, J and Hyun, S}, title = {Steroid signaling mediates nutritional regulation of juvenile body growth via IGF-binding protein in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5992-5997}, pmid = {29784791}, issn = {1091-6490}, mesh = {Animals ; *Drosophila/growth & development/metabolism/physiology ; Female ; Insulin-Like Growth Factor Binding Proteins/*metabolism ; Larva/growth & development/metabolism/physiology ; Male ; Nutritional Physiological Phenomena/*physiology ; Signal Transduction/*physiology ; Steroids/*metabolism ; }, abstract = {Nutritional condition during the juvenile growth period considerably affects final adult size. The insulin/insulin-like growth factor signaling (IIS)/target of rapamycin (TOR) nutrient-sensing pathway is known to regulate growth and metabolism in response to nutritional conditions. However, there is limited information on how endocrine pathways communicate nutritional information to different metabolic organs to regulate organismal growth. Here, we show that Imaginal morphogenesis protein-Late 2 (Imp-L2), a Drosophila homolog of insulin-like growth factor-binding protein 7 (IGFBP7), plays a key role in the nutritional control of organismal growth. Nutritional restriction during the larval growth period causes undersized adults, which is largely diminished by Imp-L2 mutation. We delineate a pathway in which nutritional restriction increases levels of the steroid hormone ecdysone, which, in turn, triggers ecdysone signaling-dependent Imp-L2 production from the fat body, a fly adipose organ, thereby attenuating peripheral IIS and body growth. Surprisingly, this endocrine pathway operates independent of the fat-body-TOR internal nutrient sensor, long believed to be the control center for nutrition-dependent growth. Our study reveals a previously unrecognized endocrine circuit mediating nutrition-dependent juvenile growth, which could also potentially be related to the insulin resistance frequently observed in puberty.}, } @article {pmid29784790, year = {2018}, author = {Bar-On, YM and Phillips, R and Milo, R}, title = {The biomass distribution on Earth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6506-6511}, pmid = {29784790}, issn = {1091-6490}, support = {R35 GM118043/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Archaea/metabolism ; Bacteria/growth & development ; *Biomass ; Biota/physiology ; Carbon/metabolism ; Earth (Planet) ; Ecosystem ; Humans ; Plants/metabolism ; }, abstract = {A census of the biomass on Earth is key for understanding the structure and dynamics of the biosphere. However, a global, quantitative view of how the biomass of different taxa compare with one another is still lacking. Here, we assemble the overall biomass composition of the biosphere, establishing a census of the ≈550 gigatons of carbon (Gt C) of biomass distributed among all of the kingdoms of life. We find that the kingdoms of life concentrate at different locations on the planet; plants (≈450 Gt C, the dominant kingdom) are primarily terrestrial, whereas animals (≈2 Gt C) are mainly marine, and bacteria (≈70 Gt C) and archaea (≈7 Gt C) are predominantly located in deep subsurface environments. We show that terrestrial biomass is about two orders of magnitude higher than marine biomass and estimate a total of ≈6 Gt C of marine biota, doubling the previous estimated quantity. Our analysis reveals that the global marine biomass pyramid contains more consumers than producers, thus increasing the scope of previous observations on inverse food pyramids. Finally, we highlight that the mass of humans is an order of magnitude higher than that of all wild mammals combined and report the historical impact of humanity on the global biomass of prominent taxa, including mammals, fish, and plants.}, } @article {pmid29784789, year = {2018}, author = {Narasimamurthy, R and Hunt, SR and Lu, Y and Fustin, JM and Okamura, H and Partch, CL and Forger, DB and Kim, JK and Virshup, DM}, title = {CK1δ/ε protein kinase primes the PER2 circadian phosphoswitch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5986-5991}, doi = {10.1073/pnas.1721076115}, pmid = {29784789}, issn = {1091-6490}, support = {R01 GM107069/GM/NIGMS NIH HHS/United States ; R01 GM121507/GM/NIGMS NIH HHS/United States ; S10 OD018455/OD/NIH HHS/United States ; }, mesh = {Animals ; Casein Kinase Idelta/*metabolism ; Casein Kinase Iepsilon/*metabolism ; Circadian Rhythm/*physiology ; HEK293 Cells ; Humans ; Mice ; Period Circadian Proteins/genetics/*metabolism ; Phosphorylation ; }, abstract = {Multisite phosphorylation of the PERIOD 2 (PER2) protein is the key step that determines the period of the mammalian circadian clock. Previous studies concluded that an unidentified kinase is required to prime PER2 for subsequent phosphorylation by casein kinase 1 (CK1), an essential clock component that is conserved from algae to humans. These subsequent phosphorylations stabilize PER2, delay its degradation, and lengthen the period of the circadian clock. Here, we perform a comprehensive biochemical and biophysical analysis of mouse PER2 (mPER2) priming phosphorylation and demonstrate, surprisingly, that CK1δ/ε is indeed the priming kinase. We find that both CK1ε and a recently characterized CK1δ2 splice variant more efficiently prime mPER2 for downstream phosphorylation in cells than the well-studied splice variant CK1δ1. While CK1 phosphorylation of PER2 was previously shown to be robust to changes in the cellular environment, our phosphoswitch mathematical model of circadian rhythms shows that the CK1 carboxyl-terminal tail can allow the period of the clock to be sensitive to cellular signaling. These studies implicate the extreme carboxyl terminus of CK1 as a key regulator of circadian timing.}, } @article {pmid29784788, year = {2018}, author = {Depner, CM and Melanson, EL and McHill, AW and Wright, KP}, title = {Mistimed food intake and sleep alters 24-hour time-of-day patterns of the human plasma proteome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5390-E5399}, pmid = {29784788}, issn = {1091-6490}, support = {P30 DK048520/DK/NIDDK NIH HHS/United States ; UL1 TR002535/TR/NCATS NIH HHS/United States ; F32 DK111161/DK/NIDDK NIH HHS/United States ; UL1 TR001082/TR/NCATS NIH HHS/United States ; R01 HL132150/HL/NHLBI NIH HHS/United States ; R21 DK092624/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Circadian Clocks ; Circadian Rhythm/physiology ; Eating/*physiology ; Healthy Volunteers ; Humans ; Male ; Melatonin/metabolism ; Plasma/chemistry/metabolism ; Proteome/*metabolism ; Sleep/*physiology ; Wakefulness/physiology ; Work Schedule Tolerance/physiology ; }, abstract = {Proteomics holds great promise for understanding human physiology, developing health biomarkers, and precision medicine. However, how much the plasma proteome varies with time of day and is regulated by the master circadian suprachiasmatic nucleus brain clock, assessed here by the melatonin rhythm, is largely unknown. Here, we assessed 24-h time-of-day patterns of human plasma proteins in six healthy men during daytime food intake and nighttime sleep in phase with the endogenous circadian clock (i.e., circadian alignment) versus daytime sleep and nighttime food intake out of phase with the endogenous circadian clock (i.e., circadian misalignment induced by simulated nightshift work). We identified 24-h time-of-day patterns in 573 of 1,129 proteins analyzed, with 30 proteins showing strong regulation by the circadian cycle. Relative to circadian alignment, the average abundance and/or 24-h time-of-day patterns of 127 proteins were altered during circadian misalignment. Altered proteins were associated with biological pathways involved in immune function, metabolism, and cancer. Of the 30 circadian-regulated proteins, the majority peaked between 1400 hours and 2100 hours, and these 30 proteins were associated with basic pathways involved in extracellular matrix organization, tyrosine kinase signaling, and signaling by receptor tyrosine-protein kinase erbB-2. Furthermore, circadian misalignment altered multiple proteins known to regulate glucose homeostasis and/or energy metabolism, with implications for altered metabolic physiology. Our findings demonstrate the circadian clock, the behavioral wake-sleep/food intake-fasting cycle, and interactions between these processes regulate 24-h time-of-day patterns of human plasma proteins and help identify mechanisms of circadian misalignment that may contribute to metabolic dysregulation.}, } @article {pmid29784787, year = {2018}, author = {}, title = {Correction for Lemos et al., CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5431-E5433}, doi = {10.1073/pnas.1807670115}, pmid = {29784787}, issn = {1091-6490}, } @article {pmid29784786, year = {2018}, author = {Fustin, JM and Kojima, R and Itoh, K and Chang, HY and Ye, S and Zhuang, B and Oji, A and Gibo, S and Narasimamurthy, R and Virshup, D and Kurosawa, G and Doi, M and Manabe, I and Ishihama, Y and Ikawa, M and Okamura, H}, title = {Two Ck1δ transcripts regulated by m6A methylation code for two antagonistic kinases in the control of the circadian clock.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5980-5985}, pmid = {29784786}, issn = {1091-6490}, mesh = {Animals ; Casein Kinase Idelta/*genetics/metabolism ; Circadian Clocks/*genetics ; Male ; *Methylation ; Methyltransferases/*genetics/metabolism ; Mice ; Mice, Inbred C57BL ; Protein Isoforms ; RNA Splicing/genetics ; RNA, Messenger/*genetics/metabolism ; }, abstract = {The N6-methylation of internal adenosines (m6A) in mRNA has been quantified and localized throughout the transcriptome. However, the physiological significance of m6A in most highly methylated mRNAs is unknown. It was demonstrated previously that the circadian clock, based on transcription-translation negative feedback loops, is sensitive to the general inhibition of m6A. Here, we show that the Casein Kinase 1 Delta mRNA (Ck1δ), coding for a critical kinase in the control of circadian rhythms, cellular growth, and survival, is negatively regulated by m6A. Inhibition of Ck1δ mRNA methylation leads to increased translation of two alternatively spliced CK1δ isoforms, CK1δ1 and CK1δ2, uncharacterized until now. The expression ratio between these isoforms is tissue-specific, CK1δ1 and CK1δ2 have different kinase activities, and they cooperate in the phosphorylation of the circadian clock protein PER2. While CK1δ1 accelerates the circadian clock by promoting the decay of PER2 proteins, CK1δ2 slows it down by stabilizing PER2 via increased phosphorylation at a key residue on PER2 protein. These observations challenge the previously established model of PER2 phosphorylation and, given the multiple functions and targets of CK1δ, the existence of two isoforms calls for a re-evaluation of past research when CK1δ1 and CK1δ2 were simply CK1δ.}, } @article {pmid29784785, year = {2018}, author = {Fernandez-Fournier, P and Guevara, J and Hoffman, C and Avilés, L}, title = {Trait overdispersion and the role of sociality in the assembly of social spider communities across the Americas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6010-6015}, doi = {10.1073/pnas.1721464115}, pmid = {29784785}, issn = {1091-6490}, mesh = {Americas ; Animals ; Behavior, Animal/*physiology ; Body Size ; Cooperative Behavior ; Ecosystem ; *Hierarchy, Social ; Phenotype ; Predatory Behavior/physiology ; *Social Behavior ; Spiders ; }, abstract = {Among the factors that may lead to differences in resource use among closely related species, body size and morphology have been traditionally considered to play a role in community assembly. Here we argue that for animals that live and forage in groups, level of sociality, reflecting differences in group size and cooperative tendencies, can be an additional and powerful dimension separating species in niche space. We compare 50+ communities of the social spider genus Anelosimus across the Americas against a null model that accounts for known effects of biotic and abiotic factors on the distribution of social systems in the genus. We show that these communities are more overdispersed than expected by chance in either or both body size and level of sociality, traits we have previously shown to be associated with differences in resource utilization (prey size, microhabitat, and phenology). We further show that the contribution of sociality to differences in the size of the prey captured is two to three times greater than that of body size, suggesting that changes in group size and cooperative tendencies may be more effective than changes in body size at separating species in niche space.}, } @article {pmid29784784, year = {2018}, author = {Dodd, T and Yan, C and Kossmann, BR and Martin, K and Ivanov, I}, title = {Uncovering universal rules governing the selectivity of the archetypal DNA glycosylase TDG.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5974-5979}, pmid = {29784784}, issn = {1091-6490}, support = {R01 GM110387/GM/NIGMS NIH HHS/United States ; }, mesh = {Cytosine/chemistry/metabolism ; DNA/*chemistry/metabolism ; Kinetics ; Markov Chains ; Molecular Dynamics Simulation ; Protein Conformation ; Substrate Specificity ; Thermodynamics ; Thymine DNA Glycosylase/*chemistry/*metabolism ; }, abstract = {Thymine DNA glycosylase (TDG) is a pivotal enzyme with dual roles in both genome maintenance and epigenetic regulation. TDG is involved in cytosine demethylation at CpG sites in DNA. Here we have used molecular modeling to delineate the lesion search and DNA base interrogation mechanisms of TDG. First, we examined the capacity of TDG to interrogate not only DNA substrates with 5-carboxyl cytosine modifications but also G:T mismatches and nonmismatched (A:T) base pairs using classical and accelerated molecular dynamics. To determine the kinetics, we constructed Markov state models. Base interrogation was found to be highly stochastic and proceeded through insertion of an arginine-containing loop into the DNA minor groove to transiently disrupt Watson-Crick pairing. Next, we employed chain-of-replicas path-sampling methodologies to compute minimum free energy paths for TDG base extrusion. We identified the key intermediates imparting selectivity and determined effective free energy profiles for the lesion search and base extrusion into the TDG active site. Our results show that DNA sculpting, dynamic glycosylase interactions, and stabilizing contacts collectively provide a powerful mechanism for the detection and discrimination of modified bases and epigenetic marks in DNA.}, } @article {pmid29784783, year = {2018}, author = {Tao, W and Díaz-Alonso, J and Sheng, N and Nicoll, RA}, title = {Postsynaptic δ1 glutamate receptor assembles and maintains hippocampal synapses via Cbln2 and neurexin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5373-E5381}, doi = {10.1073/pnas.1802737115}, pmid = {29784783}, issn = {1091-6490}, support = {R01 MH070957/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Brain/cytology/metabolism ; Cell Differentiation/physiology ; Cells, Cultured ; Hippocampus/cytology/*metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/genetics/*metabolism ; Neural Cell Adhesion Molecules/genetics/*metabolism ; Neurons/cytology/metabolism ; Protein Precursors/genetics/*metabolism ; Rats ; Receptors, Cell Surface/genetics/*metabolism ; Receptors, Glutamate/genetics/*metabolism ; Synapses/genetics/*metabolism ; Synaptic Transmission ; }, abstract = {The δ1 glutamate receptor (GluD1) was cloned decades ago and is widely expressed in many regions of the brain. However, its functional roles in these brain circuits remain unclear. Here, we find that GluD1 is required for both excitatory synapse formation and maintenance in the hippocampus. The action of GluD1 is absent in the Cbln2 knockout mouse. Furthermore, the GluD1 actions require the presence of presynaptic neurexin 1β carrying the splice site 4 insert (+S4). Together, our findings demonstrate that hippocampal synapse assembly and maintenance require a tripartite molecular complex in which the ligand Cbln2 binds with presynaptic neurexin 1β (+S4) and postsynaptic GluD1. We provide evidence that this mechanism may apply to other forebrain synapses, where GluD1 is widely expressed.}, } @article {pmid29784782, year = {2018}, author = {Sherlock, ME and Sudarsan, N and Breaker, RR}, title = {Riboswitches for the alarmone ppGpp expand the collection of RNA-based signaling systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6052-6057}, pmid = {29784782}, issn = {1091-6490}, support = {P01 GM022778/GM/NIGMS NIH HHS/United States ; R01 DE022340/DE/NIDCR NIH HHS/United States ; T32 GM007223/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Base Sequence ; Gene Expression Regulation, Bacterial ; Guanosine Tetraphosphate/genetics/metabolism/*physiology ; Ligands ; Nucleic Acid Conformation ; RNA, Bacterial ; Ribonucleotides/metabolism ; Riboswitch/genetics/*physiology ; Signal Transduction ; }, abstract = {Riboswitches are noncoding portions of certain mRNAs that bind metabolite, coenzyme, signaling molecule, or inorganic ion ligands and regulate gene expression. Most known riboswitches sense derivatives of RNA monomers. This bias in ligand chemical composition is consistent with the hypothesis that widespread riboswitch classes first emerged during the RNA World, which is proposed to have existed before proteins were present. Here we report the discovery and biochemical validation of a natural riboswitch class that selectively binds guanosine tetraphosphate (ppGpp), a widespread signaling molecule and bacterial "alarmone" derived from the ribonucleotide GTP. Riboswitches for ppGpp are predicted to regulate genes involved in branched-chain amino acid biosynthesis and transport, as well as other gene classes that previously had not been implicated to be part of its signaling network. This newfound riboswitch-alarmone partnership supports the hypothesis that prominent RNA World signaling pathways have been retained by modern cells to control key biological processes.}, } @article {pmid29784781, year = {2018}, author = {Lee, AK and Banta, AB and Wei, JH and Kiemle, DJ and Feng, J and Giner, JL and Welander, PV}, title = {C-4 sterol demethylation enzymes distinguish bacterial and eukaryotic sterol synthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5884-5889}, doi = {10.1073/pnas.1802930115}, pmid = {29784781}, issn = {1091-6490}, support = {S10 OD012254/OD/NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/genetics/*metabolism ; Computational Biology ; *Demethylation ; Escherichia coli ; Eukaryotic Cells ; Methylococcus capsulatus/*enzymology/genetics/*metabolism ; Recombinant Proteins/genetics/metabolism ; Sterols/*metabolism ; Triterpenes/metabolism ; }, abstract = {Sterols are essential eukaryotic lipids that are required for a variety of physiological roles. The diagenetic products of sterol lipids, sterane hydrocarbons, are preserved in ancient sedimentary rocks and are utilized as geological biomarkers, indicating the presence of both eukaryotes and oxic environments throughout Earth's history. However, a few bacterial species are also known to produce sterols, bringing into question the significance of bacterial sterol synthesis for our interpretation of sterane biomarkers. Recent studies suggest that bacterial sterol synthesis may be distinct from what is observed in eukaryotes. In particular, phylogenomic analyses of sterol-producing bacteria have failed to identify homologs of several key eukaryotic sterol synthesis enzymes, most notably those required for demethylation at the C-4 position. In this study, we identified two genes of previously unknown function in the aerobic methanotrophic γ-Proteobacterium Methylococcus capsulatus that encode sterol demethylase proteins (Sdm). We show that a Rieske-type oxygenase (SdmA) and an NAD(P)-dependent reductase (SdmB) are responsible for converting 4,4-dimethylsterols to 4α-methylsterols. Identification of intermediate products synthesized during heterologous expression of SdmA-SdmB along with 13C-labeling studies support a sterol C-4 demethylation mechanism distinct from that of eukaryotes. SdmA-SdmB homologs were identified in several other sterol-producing bacterial genomes but not in any eukaryotic genomes, indicating that these proteins are unrelated to the eukaryotic C-4 sterol demethylase enzymes. These findings reveal a separate pathway for sterol synthesis exclusive to bacteria and show that demethylation of sterols evolved at least twice-once in bacteria and once in eukaryotes.}, } @article {pmid29784780, year = {2018}, author = {Daley, AC and Antcliffe, JB and Drage, HB and Pates, S}, title = {Early fossil record of Euarthropoda and the Cambrian Explosion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, pmid = {29784780}, issn = {1091-6490}, abstract = {Euarthropoda is one of the best-preserved fossil animal groups and has been the most diverse animal phylum for over 500 million years. Fossil Konservat-Lagerstätten, such as Burgess Shale-type deposits (BSTs), show the evolution of the euarthropod stem lineage during the Cambrian from 518 million years ago (Ma). The stem lineage includes nonbiomineralized groups, such as Radiodonta (e.g., Anomalocaris) that provide insight into the step-by-step construction of euarthropod morphology, including the exoskeleton, biramous limbs, segmentation, and cephalic structures. Trilobites are crown group euarthropods that appear in the fossil record at 521 Ma, before the stem lineage fossils, implying a ghost lineage that needs to be constrained. These constraints come from the trace fossil record, which show the first evidence for total group Euarthropoda (e.g., Cruziana, Rusophycus) at around 537 Ma. A deep Precambrian root to the euarthropod evolutionary lineage is disproven by a comparison of Ediacaran and Cambrian lagerstätten. BSTs from the latest Ediacaran Period (e.g., Miaohe biota, 550 Ma) are abundantly fossiliferous with algae but completely lack animals, which are also missing from other Ediacaran windows, such as phosphate deposits (e.g., Doushantuo, 560 Ma). This constrains the appearance of the euarthropod stem lineage to no older than 550 Ma. While each of the major types of fossil evidence (BSTs, trace fossils, and biomineralized preservation) have their limitations and are incomplete in different ways, when taken together they allow a coherent picture to emerge of the origin and subsequent radiation of total group Euarthropoda during the Cambrian.}, } @article {pmid29784779, year = {2018}, author = {Stopa, JE and Sutherland, P and Ardhuin, F}, title = {Strong and highly variable push of ocean waves on Southern Ocean sea ice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5861-5865}, doi = {10.1073/pnas.1802011115}, pmid = {29784779}, issn = {1091-6490}, abstract = {Sea ice in the Southern Ocean has expanded over most of the past 20 y, but the decline in sea ice since 2016 has taken experts by surprise. This recent evolution highlights the poor performance of numerical models for predicting extent and thickness, which is due to our poor understanding of ice dynamics. Ocean waves are known to play an important role in ice break-up and formation. In addition, as ocean waves decay, they cause a stress that pushes the ice in the direction of wave propagation. This wave stress could not previously be quantified due to insufficient observations at large scales. Sentinel-1 synthetic aperture radars (SARs) provide high-resolution imagery from which wave height is measured year round encompassing Antarctica since 2014. Our estimates give an average wave stress that is comparable to the average wind stress acting over 50 km of sea ice. We further reveal highly variable half-decay distances ranging from 400 m to 700 km, and wave stresses from 0.01 to 1 Pa. We expect that this variability is related to ice properties and possibly different floe sizes and ice thicknesses. A strong feedback of waves on sea ice, via break-up and rafting, may be the cause of highly variable sea-ice properties.}, } @article {pmid29784778, year = {2018}, author = {Porter, LL and Looger, LL}, title = {Extant fold-switching proteins are widespread.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5968-5973}, pmid = {29784778}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Databases, Protein ; Genomics ; Humans ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; *Protein Folding ; *Protein Structure, Secondary ; Proteins/*chemistry/*metabolism ; }, abstract = {A central tenet of biology is that globular proteins have a unique 3D structure under physiological conditions. Recent work has challenged this notion by demonstrating that some proteins switch folds, a process that involves remodeling of secondary structure in response to a few mutations (evolved fold switchers) or cellular stimuli (extant fold switchers). To date, extant fold switchers have been viewed as rare byproducts of evolution, but their frequency has been neither quantified nor estimated. By systematically and exhaustively searching the Protein Data Bank (PDB), we found ∼100 extant fold-switching proteins. Furthermore, we gathered multiple lines of evidence suggesting that these proteins are widespread in nature. Based on these lines of evidence, we hypothesized that the frequency of extant fold-switching proteins may be underrepresented by the structures in the PDB. Thus, we sought to identify other putative extant fold switchers with only one solved conformation. To do this, we identified two characteristic features of our ∼100 extant fold-switching proteins, incorrect secondary structure predictions and likely independent folding cooperativity, and searched the PDB for other proteins with similar features. Reassuringly, this method identified dozens of other proteins in the literature with indication of a structural change but only one solved conformation in the PDB. Thus, we used it to estimate that 0.5-4% of PDB proteins switch folds. These results demonstrate that extant fold-switching proteins are likely more common than the PDB reflects, which has implications for cell biology, genomics, and human health.}, } @article {pmid29784777, year = {2018}, author = {Ren, Z and Lee, J and Moosa, MM and Nian, Y and Hu, L and Xu, Z and McCoy, JG and Ferreon, ACM and Im, W and Zhou, M}, title = {Structure of an EIIC sugar transporter trapped in an inward-facing conformation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5962-5967}, doi = {10.1073/pnas.1800647115}, pmid = {29784777}, issn = {1091-6490}, support = {R01 DK088057/DK/NIDDK NIH HHS/United States ; R01 GM098878/GM/NIGMS NIH HHS/United States ; R01 HL086392/HL/NHLBI NIH HHS/United States ; U54 GM087519/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus cereus/enzymology ; *Bacterial Proteins/chemistry/metabolism/ultrastructure ; Biological Transport ; Cysteine/chemistry/metabolism ; Fluorescence Resonance Energy Transfer ; Molecular Dynamics Simulation ; *Phosphoenolpyruvate Sugar Phosphotransferase System/chemistry/metabolism/ultrastructure ; Phosphorylation ; Protein Conformation ; }, abstract = {The phosphoenolpyruvate-dependent phosphotransferase system (PTS) transports sugar into bacteria and phosphorylates the sugar for metabolic consumption. The PTS is important for the survival of bacteria and thus a potential target for antibiotics, but its mechanism of sugar uptake and phosphorylation remains unclear. The PTS is composed of multiple proteins, and the membrane-embedded Enzyme IIC (EIIC) component transports sugars across the membrane. Crystal structures of two members of the glucose superfamily of EIICs, bcChbC and bcMalT, were solved in the inward-facing and outward-facing conformations, and the structures suggest that sugar translocation could be achieved by movement of a structured domain that contains the sugar-binding site. However, different conformations have not been captured on the same transporter to allow precise description of the conformational changes. Here we present a crystal structure of bcMalT trapped in an inward-facing conformation by a mercury ion that bridges two strategically placed cysteine residues. The structure allows direct comparison of the outward- and inward-facing conformations and reveals a large rigid-body motion of the sugar-binding domain and other conformational changes that accompany the rigid-body motion. All-atom molecular dynamics simulations show that the inward-facing structure is stable with or without the cross-linking. The conformational changes were further validated by single-molecule Föster resonance energy transfer (smFRET). Combined, these results establish the elevator-type mechanism of transport in the glucose superfamily of EIIC transporters.}, } @article {pmid29784776, year = {2018}, author = {Ajay, JS and Komarova, KG and Remacle, F and Levine, RD}, title = {Time-dependent view of an isotope effect in electron-nuclear nonequilibrium dynamics with applications to N2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5890-5895}, pmid = {29784776}, issn = {1091-6490}, abstract = {Isotopic fractionation in the photodissociation of N2 could explain the considerable variation in the 14N/15N ratio in different regions of our galaxy. We previously proposed that such an isotope effect is due to coupling of photoexcited bound valence and Rydberg electronic states in the frequency range where there is strong state mixing. We here identify features of the role of the mass in the dynamics through a time-dependent quantum-mechanical simulation. The photoexcitation of N2 is by an ultrashort pulse so that the process has a sharply defined origin in time and so that we can monitor the isolated molecule dynamics in time. An ultrafast pulse is necessarily broad in frequency and spans several excited electronic states. Each excited molecule is therefore not in a given electronic state but in a superposition state. A short time after excitation, there is a fairly sharp onset of a mass-dependent large population transfer when wave packets on two different electronic states in the same molecule overlap. This coherent overlap of the wave packets on different electronic states in the region of strong coupling allows an effective transfer of population that is very mass dependent. The extent of the transfer depends on the product of the populations on the two different electronic states and on their relative phase. It is as if two molecules collide but the process occurs within one molecule, a molecule that is simultaneously in both states. An analytical toy model recovers the (strong) mass and energy dependence.}, } @article {pmid29784775, year = {2018}, author = {Choi, Y and Park, TJ and Lee, DC and Lee, SY}, title = {Recombinant Escherichia coli as a biofactory for various single- and multi-element nanomaterials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5944-5949}, pmid = {29784775}, issn = {1091-6490}, mesh = {Bioreactors/microbiology ; Escherichia coli/*metabolism ; Metals, Heavy/*metabolism ; *Nanostructures ; Nanotechnology/*methods ; Oxides/metabolism ; }, abstract = {Nanomaterials (NMs) are mostly synthesized by chemical and physical methods, but biological synthesis is also receiving great attention. However, the mechanisms for biological producibility of NMs, crystalline versus amorphous, are not yet understood. Here we report biosynthesis of 60 different NMs by employing a recombinant Escherichia coli strain coexpressing metallothionein, a metal-binding protein, and phytochelatin synthase that synthesizes a metal-binding peptide phytochelatin. Both an in vivo method employing live cells and an in vitro method employing the cell extract are used to synthesize NMs. The periodic table is scanned to select 35 suitable elements, followed by biosynthesis of their NMs. Nine crystalline single-elements of Mn3O4, Fe3O4, Cu2O, Mo, Ag, In(OH)3, SnO2, Te, and Au are synthesized, while the other 16 elements result in biosynthesis of amorphous NMs or no NM synthesis. Producibility and crystallinity of the NMs are analyzed using a Pourbaix diagram that predicts the stable chemical species of each element for NM biosynthesis by varying reduction potential and pH. Based on the analyses, the initial pH of reactions is changed from 6.5 to 7.5, resulting in biosynthesis of various crystalline NMs of those previously amorphous or not-synthesized ones. This strategy is extended to biosynthesize multi-element NMs including CoFe2O4, NiFe2O4, ZnMn2O4, ZnFe2O4, Ag2S, Ag2TeO3, Ag2WO4, Hg3TeO6, PbMoO4, PbWO4, and Pb5(VO4)3OH NMs. The strategy described here allows biosynthesis of NMs with various properties, providing a platform for manufacturing various NMs in an environmentally friendly manner.}, } @article {pmid29784774, year = {2018}, author = {Start, D and McCauley, S and Gilbert, B}, title = {Physiology underlies the assembly of ecological communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6016-6021}, pmid = {29784774}, issn = {1091-6490}, mesh = {Animals ; Arginine Kinase/analysis/physiology ; Behavior, Animal/*physiology ; Biodiversity ; Biota/*physiology ; Ecosystem ; Food Chain ; Hydro-Lyases/analysis/physiology ; Larva/physiology ; Odonata/*physiology ; Phenotype ; Predatory Behavior/physiology ; }, abstract = {Trait-based community ecology promises an understanding of the factors that determine species abundances and distributions across habitats. However, ecologists are often faced with large suites of potentially important traits, making generalizations across ecosystems and species difficult or even impossible. Here, we hypothesize that key traits structuring ecological communities may be causally dependent on common physiological mechanisms and that elucidating these mechanisms can help us understand the distributions of traits and species across habitats. We test this hypothesis by investigating putatively causal relationships between physiological and behavioral traits at the species and community levels in larvae of 17 species of dragonfly that co-occur at the landscape scale but segregate among lakes. We use tools borrowed from phenotypic selection analyses to show that physiological traits underlie activity rate, which has opposing effects on foraging and predator avoidance behaviors. The effect of activity on these behaviors ultimately shapes species distributions and community composition in habitats with either large-bodied fish or invertebrates as top predators. Remarkably, despite the inherent complexity of ecological communities, the expression of just two biomolecules accounts for a high proportion of the variation in behavioral traits and hence, dragonfly community composition between habitats. We suggest that causal relationships among traits can drive species distributions and community assembly.}, } @article {pmid29784773, year = {2018}, author = {Hancock, PA and Wiebe, A and Gleave, KA and Bhatt, S and Cameron, E and Trett, A and Weetman, D and Smith, DL and Hemingway, J and Coleman, M and Gething, PW and Moyes, CL}, title = {Associated patterns of insecticide resistance in field populations of malaria vectors across Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5938-5943}, pmid = {29784773}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 AI116811/AI/NIAID NIH HHS/United States ; 108440/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Culicidae/*drug effects ; DDT/pharmacology ; Genes, Insect/*genetics ; Insecticide Resistance/*genetics ; Insecticides/*pharmacology ; *Malaria/prevention & control/transmission ; Models, Statistical ; Mosquito Vectors/*drug effects ; Nitriles/pharmacology ; Permethrin/pharmacology ; Pyrethrins/pharmacology ; }, abstract = {The development of insecticide resistance in African malaria vectors threatens the continued efficacy of important vector control methods that rely on a limited set of insecticides. To understand the operational significance of resistance we require quantitative information about levels of resistance in field populations to the suite of vector control insecticides. Estimation of resistance is complicated by the sparsity of observations in field populations, variation in resistance over time and space at local and regional scales, and cross-resistance between different insecticide types. Using observations of the prevalence of resistance in mosquito species from the Anopheles gambiae complex sampled from 1,183 locations throughout Africa, we applied Bayesian geostatistical models to quantify patterns of covariation in resistance phenotypes across different insecticides. For resistance to the three pyrethroids tested, deltamethrin, permethrin, and λ-cyhalothrin, we found consistent forms of covariation across sub-Saharan Africa and covariation between resistance to these pyrethroids and resistance to DDT. We found no evidence of resistance interactions between carbamate and organophosphate insecticides or between these insecticides and those from other classes. For pyrethroids and DDT we found significant associations between predicted mean resistance and the observed frequency of kdr mutations in the Vgsc gene in field mosquito samples, with DDT showing the strongest association. These results improve our capacity to understand and predict resistance patterns throughout Africa and can guide the development of monitoring strategies.}, } @article {pmid29784428, year = {2018}, author = {Ratajczak, Z and Carpenter, SR and Ives, AR and Kucharik, CJ and Ramiadantsoa, T and Stegner, MA and Williams, JW and Zhang, J and Turner, MG}, title = {Abrupt Change in Ecological Systems: Inference and Diagnosis.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {513-526}, doi = {10.1016/j.tree.2018.04.013}, pmid = {29784428}, issn = {1872-8383}, abstract = {Abrupt ecological changes are, by definition, those that occur over short periods of time relative to typical rates of change for a given ecosystem. The potential for such changes is growing due to anthropogenic pressures, which challenges the resilience of societies and ecosystems. Abrupt ecological changes are difficult to diagnose because they can arise from a variety of circumstances, including rapid changes in external drivers (e.g., climate, or resource extraction), nonlinear responses to gradual changes in drivers, and interactions among multiple drivers and disturbances. We synthesize strategies for identifying causes of abrupt ecological change and highlight instances where abrupt changes are likely. Diagnosing abrupt changes and inferring causation are increasingly important as society seek to adapt to rapid, multifaceted environmental changes.}, } @article {pmid29784062, year = {2018}, author = {Yeika, EV and Foryoung, JB and Efie, DT and Nkwetateba, EA and Tolefac, PN and Ngowe, MN}, title = {Multidrug resistant Proteus mirabilis and Escherichia coli causing fulminant necrotising fasciitis: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {322}, pmid = {29784062}, issn = {1756-0500}, mesh = {*Drug Resistance, Multiple, Bacterial ; Escherichia coli/*pathogenicity ; Fasciitis, Necrotizing/*diagnosis/*microbiology ; Humans ; Male ; Middle Aged ; Proteus mirabilis/*pathogenicity ; }, abstract = {BACKGROUND: Necrotizing fasciitis is a rare soft tissue infection characterized by rapid progressive necrosis with relative sparing of underlying muscles. This case is reported to highlight the emergence of multidrug resistant microbes in recent days which limits the use of empiric antibiotic therapy and necessitates early cultures and sensitivity enabling targeted antibiotic therapy. Factors that lead to antimicrobial resistance especially in sub-Saharan Africa have also been discussed.

CASE PRESENTATION: We report the case of a 52-year-old black man who was referred to our centre for the management of cellulitis and suppurating ulcers of the right leg which had progressed to a wet gangrene. Following physical examination and work-up, a diagnosis of fulminant necrotizing fasciitis of the right leg caused by multidrug resistant Proteus mirabilis and Escherichia coli was made. Despite the broad-spectrum empiric antibiotic therapy and aggressive multiple surgical debridement, necrosis progressed leading to an above-knee amputation.

CONCLUSION: Necrotizing fasciitis is a surgical emergency that requires prompt diagnosis and aggressive surgical debridement in order to reduce morbidity and mortality. The emergence of multidrug resistant organisms in recent days have limited the use of empiric antibiotic therapy, necessitating early culture and sensitivity and the use of susceptibility-guided antibiotic therapy. Timely action to control the use of antibiotics in sub-Saharan Africa will reduce multidrug resistance and delay the arrival of post-antibiotics era.}, } @article {pmid29784031, year = {2018}, author = {da Silva Paiva, L and Schoueri, JHM and de Alcantara Sousa, LV and Raimundo, RD and da Silva Maciel, E and Correa, JA and Adami, F}, title = {Regional differences in the temporal evolution of stroke: a population-based study of Brazil according to sex in individuals aged 15-49 years between 1997 and 2012.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {326}, pmid = {29784031}, issn = {1756-0500}, support = {143234 / 2016-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Adolescent ; Adult ; Brazil/epidemiology ; Humans ; Male ; Middle Aged ; Mortality/*trends ; Stroke/*mortality ; Young Adult ; }, abstract = {OBJECTIVE: The present study analyzed the temporal trend of stroke mortality according to sex in individuals aged 15-49 years in the different regions of Brazil between 1997 and 2012.

RESULTS: There was progressive reduction in mortality rate due to stroke in Brazil. The reduction trend was the same for both sexes, although mortality remained slightly higher among men. There was a difference in mortality rates according to the administrative region of the country.}, } @article {pmid29784029, year = {2018}, author = {Ratnayake, GM and Weerathunga, PN and Dilrukshi, MSA and Amara Witharana, EWR and Jayasinghe, S}, title = {Giant honey bee (Apis dorsata) sting and acute limb ischemia: a case report and review of the literature.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {327}, pmid = {29784029}, issn = {1756-0500}, mesh = {Acute Disease ; Aged ; Animals ; *Bees ; Humans ; Insect Bites and Stings/*complications ; Ischemia/*etiology ; Lower Extremity/*pathology ; Male ; }, abstract = {BACKGROUND: Clinically significant manifestations of Hymenopteran envenomation is increasingly recognized in Sri Lanka. These clinical manifestations range from localized allergic reactions to end-organ failure and thrombotic-episodes. We report a case of 65 year old male who developed acute lower limb ischaemia after a sting of the hymenopteran Apis dorsata.

CASE PRESENTATION: A 65 year old male with hypertension and hyperlipidaemia presented with envenomation from an attack of a swarm of A. dorsata. He subsequently developed acute limb ischaemia following an acute femoral thrombus and made a complete recovery with anticoagulation and surgical-embolectomy.

CONCLUSIONS: This case adds to the spectrum of thrombotic manifestations of Hymenopteran venom highlighting the requirement for close monitoring and clinical vigilance in these patients.}, } @article {pmid29784028, year = {2018}, author = {Govindarajan, R and Leela, BC and Nair, AS}, title = {RBLOSUM performs better than CorBLOSUM with lesser error per query.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {328}, pmid = {29784028}, issn = {1756-0500}, mesh = {*Algorithms ; Computational Biology/*methods ; *Databases, Protein ; Sequence Alignment/*methods ; Sequence Analysis, Protein/*methods/standards ; }, abstract = {OBJECTIVE: BLOSUM matrices serve as standard matrices for many protein sequence alignment programs. BLOSUM matrices have been constructed using BLOCKS version5.0 with 27,102 BLOCKS, whereas the latest updated version14.3 has 6,739,916 BLOCKS. We read with interest the research article by Hess et al. (BMC Bioinform 17:189, 2016) on CorBLOSUM, wherein it is argued that an inaccuracy in the BLOSUM code affects the cluster memberships of sequences. They show that replacing the integer based clustering threshold to floating point arguably improves the performances of CorBLOSUM over BLOSUM and RBLOSUM matrices. They compare BLOSUM6214.3 against RBLOSUM69, with relative entropies of 0.2685 and 0.2662 respectively. The present work attempts to repeat the computation to verify the respective analog matrices.

RESULTS: In our attempt to repeat the computation, we observed that the relative entropy of BLOSUM6214.3 is 0.2360 and BLOSUM5014.3 is 0.1198. As only matrices of similar entropies can be compared, BLOSUM62 can be compared only with RBLOSUM66 and BLOSUM50 can be compared only with RBLOSUM56. We conducted experiments with Astral data sets, and demonstrated the improved accuracy in the coverage. Our results imply that RBLOSUM performs statistically better than CorBLOSUM and BLOSUM matrices.}, } @article {pmid29784027, year = {2018}, author = {Beissbarth, J and Binks, MJ and Marsh, RL and Chang, AB and Leach, AJ and Smith-Vaughan, HC}, title = {Recommendations for application of Haemophilus influenzae PCR diagnostics to respiratory specimens for children living in northern Australia: a retrospective re-analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {323}, pmid = {29784027}, issn = {1756-0500}, mesh = {Australia ; Child ; Child, Preschool ; Female ; Guidelines as Topic/standards ; Haemophilus Infections/*microbiology ; Haemophilus influenzae/*isolation & purification ; Humans ; Infant ; Male ; Polymerase Chain Reaction/*standards ; Respiratory Tract Infections/*microbiology ; Retrospective Studies ; }, abstract = {OBJECTIVE: Haemophilus haemolyticus can be misidentified as nontypeable Haemophilus influenzae (NTHi) due to their phenotypic similarities in microbiological culture. This study aimed to determine the prevalence of misidentified NTHi in respiratory specimens from children living in northern Australia.

RESULTS: Among respiratory specimens collected in studies between 2010 and 2013, retrospective PCR analysis found that routine culture misidentified H. haemolyticus as NTHi in 0.3% (3/879) of nasal specimens, 25% (14/55) of bronchoalveolar lavage and 40% (12/30) of throat specimens. Therefore, in this population, PCR-based NTHi diagnostics are indicated for throat and bronchoalveolar specimens, but not for nasal specimens.}, } @article {pmid29784026, year = {2018}, author = {Murad, H and Alghamian, Y and Aljapawe, A and Madania, A}, title = {Effects of ionizing radiation on the viability and proliferative behavior of the human glioblastoma T98G cell line.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {330}, pmid = {29784026}, issn = {1756-0500}, mesh = {Apoptosis/*radiation effects ; Cell Cycle/*radiation effects ; Cell Line, Tumor/*radiation effects ; Cell Survival/*radiation effects ; Central Nervous System Neoplasms/*radiotherapy ; Flow Cytometry ; Glioblastoma/*radiotherapy ; Humans ; *Radiation, Ionizing ; }, abstract = {OBJECTIVE: Radiotherapy is the traditional therapy for glioma patients. Glioma has poor response to ionizing radiation (IR). Studying radiation-induced cell death can help in understanding the cellular mechanisms underlying its radioresistance. T98G cell line was irradiated with Co60 source by 2 or 10 Gy. MTT assay was used to calculate the surviving fraction. Cell viability, cell cycle distribution and apoptosis assays were conducted by flow cytometry for irradiated and control cells for the 10 Gy dose.

RESULTS: The SF2 value for irradiated cells was 0.8. Cell viability was decreased from 93.29 to 73.61%, while, the Sub G0/G1 phase fraction was significantly increased at 10 Gy after 48 h. On the other hand, there was an increase in the percentage of apoptotic cells which reached 40.16% after 72 h at the same dose, while, it did not exceeds 2% for non-irradiated cells. Our results showed that, the T98G cells is radioresistant to IR up to 10 Gy. Effects of irradiation on the viability of T98G cells were relatively mild, since entering apoptosis was delayed for about 3 days after irradiation.}, } @article {pmid29784022, year = {2018}, author = {Khanra, S and Kumar, YP and Dash, J and Banerjee, R}, title = {In vitro screening of known drugs identified by scaffold hopping techniques shows promising leishmanicidal activity for suramin and netilmicin.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {319}, pmid = {29784022}, issn = {1756-0500}, mesh = {Animals ; Antiprotozoal Agents/*pharmacology ; Cell Line, Tumor ; Drug Evaluation, Preclinical/*methods ; *Drug Synergism ; Leishmania/*drug effects ; Leishmaniasis/*drug therapy ; Mice ; Netilmicin/*pharmacology ; Suramin/*pharmacology ; }, abstract = {OBJECTIVE: The rapid emergence of drug resistant Leishmanial strains makes it imperative to continue the development of cheap and effective drugs against the parasite. Due to the absence of effective vaccines against leishmaniasis, current therapeutic measures exclusively rely on chemotherapy. Here we attempt, to identify novel antileishmanial from a list of known drugs determined from a previous bioinformatics study. Synergism between various drug combinations (involving netilmicin, suramin, paromomycin and curcumin) have been estimated to identify potent multidrug therapies to combat the disease.

RESULTS: The drugs were screened against Leishmania promastigotes by utilizing the MTT assay and against intracellular amastigotes using murine Macrophage like tumor cell, RAW 264.7 as a host. In vitro drug interactions were tested for several drug combinations with a modified fixed ratio isobologram method against both Leishmania major and Leishmania donovani. This work reports the in vitro antileishmanial activity for the aminoglycoside netilmicin (for some Leishmania parasites) and the anti-trypanosomatid suramin. Synergism was also observed between paromomycin-suramin and netilmicin-curcumin.}, } @article {pmid29784021, year = {2018}, author = {Johnson, RE and Oyebode, O and Walker, S and Knowles, E and Robertson, W}, title = {The difficult conversation: a qualitative evaluation of the 'Eat Well Move More' family weight management service.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {325}, pmid = {29784021}, issn = {1756-0500}, support = {wmclahrc-2014-1//National Institute for Health Research/ ; }, mesh = {Adolescent ; Child ; Child, Preschool ; *Exercise ; *Family ; Female ; *Health Communication ; Health Education/*methods ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Pediatric Obesity/*therapy ; Qualitative Research ; *School Health Services ; Weight Reduction Programs/*methods ; }, abstract = {OBJECTIVE: The Eat Well Move More (EWMM) family and child weight management service is a 12-week intervention integrating healthy eating and physical activity education and activities for families and children aged 4-16. EWMM service providers identified low uptake 12 months prior to the evaluation. The aims of this study were to describe referral practices and pathways into the service to identify potential reasons for low referral and uptake rates.

RESULTS: We conducted interviews and focus groups with general practitioners (GPs) (n = 4), school nurses, and nursing assistants (n = 12). Data were analysed using thematic analysis. School nurses highlighted three main barriers to making a referral: parent engagement, child autonomy, and concerns over the National Child Measurement Programme letter. GPs highlighted that addressing obesity among children is a 'difficult conversation' with several complex issues related to and sustaining that difficulty. In conclusion, referral into weight management services in the community may persistently lag if a larger and more complex tangle of barriers lie at the point of school nurse and GP decision-making. The national prevalence of, and factors associated with this hesitation to discuss weight management issues with parents and children remains largely unknown.}, } @article {pmid29784020, year = {2018}, author = {Hashmi, KA and Shehzad, A and Hashmi, AA and Khan, A}, title = {Atrioventricular block after acute myocardial infarction and its association with other clinical parameters in Pakistani patients: an institutional perspective.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {329}, pmid = {29784020}, issn = {1756-0500}, mesh = {Adult ; Atrioventricular Block/epidemiology/*etiology ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Pakistan/epidemiology ; Risk Factors ; ST Elevation Myocardial Infarction/*complications/epidemiology ; }, abstract = {OBJECTIVES: Conduction defects complicating acute myocardial infarction are frequently associated with increased morbidity and mortality. As frequency of this complication has not been widely studied in our population, therefore in this study we aimed to evaluate the frequency of complete atrioventricular block in patients with acute ST segment elevation myocardial infarction and its association with other clinical parameters.

RESULTS: The mean age of the patients was 50.55 ± 6.72 years at the time of MI. There were 147 (82.1%) males and 32 (17.9%) females. There were 83 (46.4%) patients having hypertension, 61 (34.1%) diabetes mellitus, 75 (41.9%) smokers, 75 (41.9%) patients having positive family history, 11 (6.1%) having dyslipidemia, and 73 (40.8%) obese patients in this study. The Frequency of complete atrioventricular (AV) block in acute ST segment elevation myocardial infarction was found to be 7.3%, and no association with any other clinical factor was found which could predict this condition according to results of our study. Therefore, protocols should be designed in our routine clinical practice to deal with such a life threatening condition.}, } @article {pmid29784018, year = {2018}, author = {Asano, T and Furuya, MY and Sato, S and Kobayashi, H and Watanabe, H and Suzuki, E and Migita, K}, title = {Adding colchicine to immunosuppressive treatments; a potential option for biologics-refractory adult-onset Still's disease.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {320}, pmid = {29784018}, issn = {1756-0500}, mesh = {Adult ; Anti-Inflammatory Agents/administration & dosage/*pharmacology ; Colchicine/administration & dosage/*pharmacology ; Drug Therapy, Combination ; Female ; Humans ; Immunosuppressive Agents/administration & dosage/*pharmacology ; Still's Disease, Adult-Onset/*drug therapy ; Young Adult ; }, abstract = {BACKGROUND: Adult-onset Still's disease (AOSD) is a rare inflammatory disorder characterized by the classical triad of daily spiking fever, arthritis, and typical salmon-colored rash. Resistance to first-line corticosteroids and second-line disease modified anti-rheumatic-drugs defines refractory AOSD, which mostly includes the polycyclic or chronic courses of the disease. Anti-cytokine therapies are recommended in AOSD patients who are refractory to traditional treatments. This is the first report on the efficacy of colchicine in a patient with AOSD which was refractory to immunosuppressive treatments including biologics.

CASE PRESENTATION: A 24-years Japanese female patient was referred to our hospital for the flare-up of AOSD under the combined treatments with steroid, immunosuppressants, and biologics. She was diagnosed with AOSD according to the Yamaguchi criteria, based on the presence of spiking fever, polyarthralgia, skin rash, and hyperferritinemia. Interleukin-6 or tumor necrosis factor-α blockade treatments were not effective, the oral administration of colchicine was stared under the immunosuppressive treatments with steroid and cyclosporine A (CyA). Colchicine treatment silenced the disease activity of AOSD. The dose of prednisolone was successfully tapered, and the elevated levels of C-reactive protein were normalized. Remission has been maintained for 13 months with the start of oral administration of colchicine.

CONCLUSION: We concluded that colchicine is an alternative treatment in patients with refractory AOSD, particularly in those with impaired therapeutic effects against anti-cytokines therapies.}, } @article {pmid29784017, year = {2018}, author = {Mahato, S and Mahato, A and Karna, PK and Balmiki, N}, title = {Investigating aquifer contamination and groundwater quality in eastern Terai region of Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {321}, pmid = {29784017}, issn = {1756-0500}, mesh = {Drinking Water/*analysis ; Electric Conductivity ; Groundwater/*analysis ; Nepal ; Water Pollutants, Chemical/*analysis ; }, abstract = {OBJECTIVE: This study aims at assessing the groundwater quality of the three districts of Eastern Terai region of Nepal viz. Morang, Jhapa, Sunsari using physicochemical characteristics and statistical approach so that possible contamination of water reservoir can be understood. pH, temperature, conductivity, turbidity, color, total dissolved solids, fluorides, ammonia, nitrates, chloride, total hardness, calcium hardness, calcium, magnesium, total alkalinity, iron, manganese, arsenic have to be analyzed to know the present status of groundwater quality.

RESULTS: Results revealed that the value of analyzed parameters were within the acceptable limits for drinking water recommended by World Health Organization except for pH, turbidity, ammonia and iron. As per Nepal Drinking Water Quality Standards, fluoride and manganese too were not complying with the permissible limit. Electrical conductivity, total dissolved solids, chloride, total hardness, calcium hardness, manganese, and total alkalinity show good positive correlation with major water quality parameters. Calcium, magnesium, total hardness, calcium hardness and total alkalinity greatly influences total dissolved solids and electrical conductivity. ANOVA, Tukey, and clustering highlight the significance of three districts. Groundwater can be considered safe, but there is always a chance of contamination through chemical wastes in the heavily industrialized area of Morang and Sunsari Industrial corridor.}, } @article {pmid29784014, year = {2018}, author = {Gunaratne, K and Austin, E and Wu, PE}, title = {Unintentional sulfonylurea toxicity due to a drug-drug interaction: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {331}, pmid = {29784014}, issn = {1756-0500}, mesh = {Antifungal Agents/*pharmacology ; Diabetes Mellitus, Type 2/*drug therapy ; *Drug Interactions ; Fluconazole/pharmacology ; Gliclazide/*toxicity ; Humans ; Hypoglycemic Agents/*toxicity ; Lung Diseases, Fungal/*drug therapy ; Male ; Middle Aged ; Pneumonia/*drug therapy ; Sulfonylurea Compounds/*toxicity ; Voriconazole/pharmacology ; }, abstract = {BACKGROUND: Sulfonylureas are widely used for type 2 diabetes mellitus, but these medications carry a risk of hypoglycemia. Drug-drug interactions that inhibit sulfonylurea metabolism and thus increase systemic exposure can cause unintentional sulfonylurea toxicity.

CASE PRESENTATION: A 56-year-old man presented with severe, recurrent hypoglycemia. He had a history of type 2 diabetes mellitus and was taking the sulfonylurea gliclazide with no prior episodes of hypoglycemia. The onset of his hypoglycemia occurred within days after starting voriconazole and subsequently fluconazole for a fungal pneumonia. Unintentional sulfonylurea toxicity developed due to an adverse drug-drug interaction between gliclazide and these antifungals. Azole antifungals inhibit the metabolism of sulfonylureas resulting in increased systemic exposure and consequent toxicity. After the diagnosis of sulfonylurea toxicity was recognized, the patient was treated initially with dextrose and then administered octreotide to prevent recurrent hypoglycemia. He was successfully managed, his hypoglycemic episodes resolved, and his medications were adjusted to avoid any further adverse interactions.

CONCLUSIONS: Adverse drug-drug interactions continue to pose challenges to clinicians. Both individual vigilance and system wide strategies are needed to prevent and mitigate consequences. This case highlights an important drug-drug interaction and reviews the presentation, management and antidotal therapy of sulfonylurea toxicity.}, } @article {pmid29784013, year = {2018}, author = {Capossela, S and Bertolo, A and Gunasekera, K and Pötzel, T and Baur, M and Stoyanov, JV}, title = {VEGF vascularization pathway in human intervertebral disc does not change during the disc degeneration process.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {333}, pmid = {29784013}, issn = {1756-0500}, support = {CR2313_159744//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Animals ; Cattle ; Gene Expression/*physiology ; Humans ; Intervertebral Disc/*metabolism ; Intervertebral Disc Degeneration/*metabolism ; Microarray Analysis/*methods ; Neovascularization, Pathologic/*metabolism ; Real-Time Polymerase Chain Reaction ; Vascular Endothelial Growth Factor Receptor-1/*metabolism ; }, abstract = {OBJECTIVE: During degeneration of the intervertebral disc ingrowth of blood vessels and nerves into the disc are associated with back pain. Vascular endothelial growth factors promote vasculogenesis by binding to the membrane vascular endothelial growth factor receptor 1, while shorter soluble forms of this receptor can inhibit vascularization. We hypothesized that membrane and soluble receptor forms might change between stages of intervertebral disc degeneration.

RESULTS: Expression of soluble and membrane forms of vascular endothelial growth factor receptor 1 in human degenerated intervertebral discs and healthy bovine caudal discs was assessed by qRT-PCR and immunoblot. Comparative microarray meta-analysis across disc degeneration grades showed that membrane and soluble forms of this receptor, together with other components of classic vascularization pathways, are constitutively expressed across human disc degeneration stages. Contrary to our hypothesis, we observed that expression of the classic vascularization pathway is stable across degeneration stages and we assume that soluble vascular endothelial growth factor receptor 1 does not contribute to prevent disc degeneration. However, we observed increased expression levels of genes involved in alternative vascularization signalling pathways in severely degenerated discs, suggesting that abnormal vascularization is part of the pathological progression of disc degeneration.}, } @article {pmid29784010, year = {2018}, author = {Ikhtiar, AM and Jazairi, B and Khansa, I and Othman, A}, title = {HLA class I alleles frequencies in the Syrian population.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {324}, pmid = {29784010}, issn = {1756-0500}, mesh = {Gene Frequency ; Genetics, Population ; HLA-A Antigens/*genetics ; HLA-B Antigens/*genetics ; HLA-C Antigens/*genetics ; Haplotypes ; Humans ; Syria ; }, abstract = {OBJECTIVE: The HLA system is known to be the most polymorphic genetic loci in humans. Distribution and frequencies of HLA alleles are highly variable among different human ethnic groups. The HLA system has an important role in disease susceptibility and resistance, especially in autoimmune diseases and cancer. This study is the first report about HLA genetic variability and haplotypes among Syrians. Frequency of the HLA class I (A, B and C) alleles was determined in 105 healthy unrelated Syrian individuals from different regions in Syria. We also studied the associated haplotypes frequencies. Alleles frequencies were compared with those reported for other populations.

RESULTS: Fifty-eight HLA class I alleles were observed in Syrians including 15 for HLA-A, 28 for HLA-B and 15 for HLA-C. We observed 37 HLA-A/C haplotypes, 32 B/C, and 31 A/B haplotypes. The most frequent haplotypes were A*01/C*04, A*02/C*07, A*02/B*35, and B*35/C*04. In conclusions, our preliminary study suggests a high variability in HLA class I alleles in the Syrian population. This study also gives a general reference database about the genetic pool distribution of HLA class I alleles among Syrians and can be consulted for HLA related diseases.}, } @article {pmid29784009, year = {2018}, author = {Reder, M and Thygesen, LC}, title = {Crowd-figure-pictograms improve women's knowledge about mammography screening: results from a randomised controlled trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {332}, pmid = {29784009}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Breast Neoplasms/*diagnostic imaging ; Early Detection of Cancer/*psychology ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Mammography/*psychology ; Middle Aged ; Patient Education as Topic/*methods ; Young Adult ; }, abstract = {OBJECTIVE: To evaluate the effect of crowd-figure-pictograms on women's numeric knowledge about mammography screening in a three-armed parallel randomised controlled trial.

RESULTS: 552 women were randomised to receive (1) non-numeric information (n = 192), (2) non-numeric and numeric information (n = 186), or (3) non-numeric and numeric information complemented by crowd-figure-pictograms (n = 174). Baseline numeric knowledge was low (control 0.61, numeric 0.66, and pictogram 0.51 on a scale ranging from 0 to 5). Women in the crowd-figure-pictogram group had a larger knowledge increase than women in the numeric group (2.42 vs 2.06, p = .03). Both groups had significant increases in knowledge compared to the control (0.20, p < .001). Providing numeric information in absolute numbers improves knowledge; even more so when crowd-figure-pictograms are added. Trial registration German Clinical Trials Register DRKS00014736, retrospectively registered 11 May 2018.}, } @article {pmid29783978, year = {2018}, author = {Paule, J and Dunkel, FG and Schmidt, M and Gregor, T}, title = {Climatic differentiation in polyploid apomictic Ranunculus auricomus complex in Europe.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {16}, pmid = {29783978}, issn = {1472-6785}, support = {ZI 557/13-1//Deutsche Forschungsgemeinschaft/International ; }, abstract = {BACKGROUND: Polyploidy and apomixis are important factors influencing plant distributions often resulting in range shifts, expansions and geographical parthenogenesis. We used the Ranunculus auricomus complex as a model to asses if the past and present distribution and climatic preferences were determined by these phenomena.

RESULTS: Ecological differentiation among diploids and polyploids was tested by comparing the sets of climatic variables and distribution modelling using 191 novel ploidy estimations and 561 literature data. Significant differences in relative genome size on the diploid level were recorded between the "auricomus" and "cassubicus" groups and several new diploid occurrences were found in Slovenia and Hungary. The current distribution of diploids overlapped with the modelled paleodistribution (22 kyr BP), except Austria and the Carpathians, which are proposed to be colonized later on from refugia in the Balkans. Current and historical presence of diploids from the R. auricomus complex is suggested also for the foothills of the Caucasus. Based on comparisons of the climatic preferences polyploids from the R. auricomus complex occupy slightly drier and colder habitats than the diploids.

CONCLUSIONS: The change of reproductive mode and selection due to competition with the diploid ancestors may have facilitated the establishment of polyploids within the R. auricomus complex in environments slightly cooler and drier, than those tolerated by diploid ancestors. Much broader distribution of polyploid apomicts may have been achieved due to faster colonization mediated by uniparental reproductive system.}, } @article {pmid29783957, year = {2018}, author = {Di, Z and Edgecombe, GD and Sharma, PP}, title = {Homeosis in a scorpion supports a telopodal origin of pectines and components of the book lungs.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {73}, pmid = {29783957}, issn = {1471-2148}, support = {31601871//National Natural Science Foundation of China/International ; 8137379//National Natural Science Foundation of China/International ; IOS-1552610//National Science Foundation/International ; 1708085QC54//Natural Science Foundation of Anhui Province/International ; }, mesh = {Animals ; *Biological Evolution ; Extremities/anatomy & histology ; Fossils ; *Genes, Homeobox ; Gills/*anatomy & histology ; Phenotype ; Scorpions/*anatomy & histology/embryology/*genetics ; }, abstract = {BACKGROUND: The morphological and functional evolution of appendages has played a key role in the diversification of arthropods. While the ancestral arthropod appendage is held to be polyramous, terrestriality is associated with the reduction or loss of appendage rami, which may obscure the homology of different appendage derivatives. Proxies for appendage homology have included surveys of cross-reactive antibodies for wing markers like Nubbin/PDM, which have suggested that the abdominal appendages of arachnids (e.g., book lungs, tracheal tubules) are derived from ancestral gills (epipods).

RESULTS: Here, we discovered a rare case of inferred homeosis in a scorpion in which the bilobed genital opercula and the pectines are transformed to walking legs, and an abnormal sternite shows a book lung close to an everted structure comparable to the morphology of some Palaeozoic scorpion fossils.

CONCLUSIONS: The observed morphology is consistent with abnormal expression of homeotic genes during embryonic development. The phenotype of this abnormal specimen suggests that the genital opercula, the pectines, and parts of the book lung may be derived from the telopodite of abdominal appendages rather than from epipods. This interpretation contradicts the "ancestral gill" hypothesis but reconciles features of the Palaeozoic scorpion fossil record with the embryology of modern scorpions.}, } @article {pmid29783952, year = {2018}, author = {Sun, X and Liu, Z and Wu, B and Zhou, L and Wang, Q and Wu, W and Yang, A}, title = {Differences between fast and slow muscles in scallops revealed through proteomics and transcriptomics.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {377}, pmid = {29783952}, issn = {1471-2164}, support = {31602153//National Natural Science Foundation of China (CN)/ ; ZR2016CQ32//Natural Science Foundation of Shandong Province/ ; KLM2018004//the Key Laboratory of Mariculture, Ministry of Education, Ocean University of China/ ; 2016LMFS-B02//Laboratory for Marine Fisheries Science and Food Production Processes, Qingdao National Laboratory for Marine Science and Technology, China P. R. China/ ; }, mesh = {Animals ; *Gene Expression Profiling ; Muscle, Striated/*metabolism ; Pectinidae/*genetics/*metabolism ; *Proteomics ; }, abstract = {BACKGROUND: Scallops possess striated and catch adductor muscles, which have different structure and contractile properties. The striated muscle contracts very quickly for swimming, whereas the smooth catch muscle can keep the shells closed for long periods with little expenditure of energy. In this study, we performed proteomic and transcriptomic analyses of differences between the striated (fast) and catch (slow) adductor muscles in Yesso scallop Patinopecten yessoensis.

RESULTS: Transcriptomic analysis reveals 1316 upregulated and 8239 downregulated genes in slow compared to fast adductor muscle. For the same comparison, iTRAQ-based proteomics reveals 474 differentially expressed proteins (DEPs), 198 up- and 276 downregulated. These DEPs mainly comprise muscle-specific proteins of the sarcoplasmic reticulum, extracellular matrix, and metabolic pathways. A group of conventional muscle proteins-myosin heavy chain, myosin regulatory light chain, myosin essential light chain, and troponin-are enriched in fast muscle. In contrast, paramyosin, twitchin, and catchin are preferentially expressed in slow muscle. The association analysis of proteomic and transcriptomic data provides the evidences of regulatory events at the transcriptional and posttranscriptional levels in fast and slow muscles. Among 1236 differentially expressed unigenes, 22.7% show a similar regulation of mRNA levels and protein abundances. In contrast, more unigenes (53.2%) exhibit striking differences between gene expression and protein abundances in the two muscles, which indicates the existence of fiber-type specific, posttranscriptional regulatory events in most of myofibrillar proteins, such as myosin heavy chain, titin, troponin, and twitchin.

CONCLUSIONS: This first, global view of protein and mRNA expression levels in scallop fast and slow muscles reveal that regulatory mechanisms at the transcriptional and posttranscriptional levels are essential in the maintenance of muscle structure and function. The existence of fiber-type specific, posttranscriptional regulatory mechanisms in myofibrillar proteins will greatly improve our understanding of the molecular basis of muscle contraction and its regulation in non-model invertebrates.}, } @article {pmid29783951, year = {2018}, author = {Becker, D and Reydelet, Y and Lopez, JA and Jackson, C and Colbourne, JK and Hawat, S and Hippler, M and Zeis, B and Paul, RJ}, title = {The transcriptomic and proteomic responses of Daphnia pulex to changes in temperature and food supply comprise environment-specific and clone-specific elements.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {376}, pmid = {29783951}, issn = {1471-2164}, support = {Pa 308/15-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Acclimatization/genetics ; Animals ; Daphnia/*genetics/*physiology ; *Environment ; Food Supply ; *Gene Expression Profiling ; Heat-Shock Response/genetics ; *Proteomics ; *Temperature ; }, abstract = {BACKGROUND: Regulatory adjustments to acute and chronic temperature changes are highly important for aquatic ectotherms because temperature affects their metabolic rate as well as the already low oxygen concentration in water, which can upset their energy balance. This also applies to severe changes in food supply. Thus, we studied on a molecular level (transcriptomics and/or proteomics) the immediate responses to heat stress and starvation and the acclimation to different temperatures in two clonal isolates of the model microcrustacean Daphnia pulex from more or less stressful environments, which showed a higher (clone M) or lower (clone G) tolerance to heat and starvation.

RESULTS: The transcriptomic responses of clone G to acute heat stress (from 20 °C to 30 °C) and temperature acclimation (10 °C, 20 °C, and 24 °C) and the proteomic responses of both clones to acute heat, starvation, and heat-and-starvation stress comprised environment-specific and clone-specific elements. Acute stress (in particular heat stress) led to an early upregulation of stress genes and proteins (e.g., molecular chaperones) and a downregulation of metabolic genes and proteins (e.g., hydrolases). The transcriptomic responses to temperature acclimation differed clearly. They also varied depending on the temperature level. Acclimation to higher temperatures comprised an upregulation of metabolic genes and, in case of 24 °C acclimation, a downregulation of genes for translational processes and collagens. The proteomic responses of the clones M and G differed at any type of stress. Clone M showed markedly stronger and less stress-specific proteomic responses than clone G, which included the consistent expression of a specific heat shock protein (HSP60) and vitellogenin (VTG-SOD).

CONCLUSIONS: The expression changes under acute stress can be interpreted as a switch from standard products of gene expression to stress-specific products. The expression changes under temperature acclimation probably served for an increase in energy intake (via digestion) and, if necessary, a decrease in energy expenditures (e.g, for translational processes). The stronger and less stress-specific proteomic responses of clone M indicate a lower degree of cell damage and an active preservation of the energy balance, which allowed adequate proteomic responses under stress, including the initiation of resting egg production (VTG-SOD expression) as an emergency reaction.}, } @article {pmid29783949, year = {2018}, author = {Simam, J and Rono, M and Ngoi, J and Nyonda, M and Mok, S and Marsh, K and Bozdech, Z and Mackinnon, M}, title = {Gene copy number variation in natural populations of Plasmodium falciparum in Eastern Africa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {372}, pmid = {29783949}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; 088634//Wellcome Trust/United Kingdom ; 092741//Wellcome Trust/United Kingdom ; 077176//Wellcome Trust (GB)/ ; }, mesh = {Adaptation, Physiological/genetics ; Africa, Eastern ; Child ; Child, Preschool ; Chromosome Deletion ; *DNA Copy Number Variations ; Female ; Humans ; Infant ; Male ; Plasmodium falciparum/*genetics/physiology ; }, abstract = {BACKGROUND: Gene copy number variants (CNVs), which consist of deletions and amplifications of single or sets of contiguous genes, contribute to the great diversity in the Plasmodium falciparum genome. In vitro studies in the laboratory have revealed their important role in parasite fitness phenotypes such as red cell invasion, transmissibility and cytoadherence. Studies of natural parasite populations indicate that CNVs are also common in the field and thus may facilitate adaptation of the parasite to its local environment.

RESULTS: In a survey of 183 fresh field isolates from three populations in Eastern Africa with different malaria transmission intensities, we identified 94 CNV loci using microarrays. All CNVs had low population frequencies (minor allele frequency < 5%) but each parasite isolate carried an average of 8 CNVs. Nine CNVs showed high levels of population differentiation (FST > 0.3) and nine exhibited significant clines in population frequency across a gradient in transmission intensity. The clearest example of this was a large deletion on chromosome 9 previously reported only in laboratory-adapted isolates. This deletion was present in 33% of isolates from a population with low and highly seasonal malaria transmission, and in < 9% of isolates from populations with higher transmission. Subsets of CNVs were strongly correlated in their population frequencies, implying co-selection.

CONCLUSIONS: These results support the hypothesis that CNVs are the target of selection in natural populations of P. falciparum. Their environment-specific patterns observed here imply an important role for them in conferring adaptability to the parasite thus enabling it to persist in its highly diverse ecological environment.}, } @article {pmid29783948, year = {2018}, author = {Krin, E and Pierlé, SA and Sismeiro, O and Jagla, B and Dillies, MA and Varet, H and Irazoki, O and Campoy, S and Rouy, Z and Cruveiller, S and Médigue, C and Coppée, JY and Mazel, D}, title = {Expansion of the SOS regulon of Vibrio cholerae through extensive transcriptome analysis and experimental validation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {373}, pmid = {29783948}, issn = {1471-2164}, mesh = {5' Untranslated Regions/genetics ; *Gene Expression Profiling ; Mitomycin/pharmacology ; Phenotype ; Regulon/*genetics ; SOS Response (Genetics)/drug effects/*genetics ; Transcription Initiation Site/drug effects ; Vibrio cholerae/drug effects/*genetics ; }, abstract = {BACKGROUND: The SOS response is an almost ubiquitous response of cells to genotoxic stresses. The full complement of genes in the SOS regulon for Vibrio species has only been addressed through bioinformatic analyses predicting LexA binding box consensus and in vitro validation. Here, we perform whole transcriptome sequencing from Vibrio cholerae treated with mitomycin C as an SOS inducer to characterize the SOS regulon and other pathways affected by this treatment.

RESULTS: Comprehensive transcriptional profiling allowed us to define the full landscape of promoters and transcripts active in V. cholerae. We performed extensive transcription start site (TSS) mapping as well as detection/quantification of the coding and non-coding RNA (ncRNA) repertoire in strain N16961. To improve TSS detection, we developed a new technique to treat RNA extracted from cells grown in various conditions. This allowed for identification of 3078 TSSs with an average 5'UTR of 116 nucleotides, and peak distribution between 16 and 64 nucleotides; as well as 629 ncRNAs. Mitomycin C treatment induced transcription of 737 genes and 28 ncRNAs at least 2 fold, while it repressed 231 genes and 17 ncRNAs. Data analysis revealed that in addition to the core genes known to integrate the SOS regulon, several metabolic pathways were induced. This study allowed for expansion of the Vibrio SOS regulon, as twelve genes (ubiEJB, tatABC, smpA, cep, VC0091, VC1190, VC1369-1370) were found to be co-induced with their adjacent canonical SOS regulon gene(s), through transcriptional read-through. Characterization of UV and mitomycin C susceptibility for mutants of these newly identified SOS regulon genes and other highly induced genes and ncRNAs confirmed their role in DNA damage rescue and protection.

CONCLUSIONS: We show that genotoxic stress induces a pervasive transcriptional response, affecting almost 20% of the V. cholerae genes. We also demonstrate that the SOS regulon is larger than previously known, and its syntenic organization is conserved among Vibrio species. Furthermore, this specific co-localization is found in other γ-proteobacteria for genes recN-smpA and rmuC-tatABC, suggesting SOS regulon conservation in this phylum. Finally, we comment on the limitations of widespread NGS approaches for identification of all RNA species in bacteria.}, } @article {pmid29783946, year = {2018}, author = {Burnett, PG and Young, LW and Olivia, CM and Jadhav, PD and Okinyo-Owiti, DP and Reaney, MJT}, title = {Novel flax orbitide derived from genetic deletion.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {90}, pmid = {29783946}, issn = {1471-2229}, support = {1309//Genome Canada/ ; ADF Grant 20080205//Ministry of Agriculture - Saskatchewan/ ; ADF Grant 20120099//Ministry of Agriculture - Saskatchewan/ ; ADF Grant 20120146//Ministry of Agriculture - Saskatchewan/ ; }, mesh = {Amino Acid Sequence ; Chromatography, High Pressure Liquid ; Flax/*chemistry/genetics ; Genetic Variation ; Magnetic Resonance Spectroscopy ; Mass Spectrometry ; Peptides, Cyclic/*chemistry/genetics/isolation & purification ; *Protein Processing, Post-Translational ; Seeds/chemistry/genetics ; Sequence Analysis, DNA ; Sequence Deletion ; }, abstract = {BACKGROUND: Flaxseed orbitides are homodetic plant cyclic peptides arising from ribosomal synthesis and post-translation modification (N to C cyclization), and lacking cysteine double bonds (Nat Prod Rep 30:108-160, 2013). Screening for orbitide composition was conducted on the flax core collection (FCC) grown at both Saskatoon, Saskatchewan and Morden, Manitoba over three growing seasons (2009-2011). Two flax (Linum usitatissimum L.) accessions 'Hollandia' (CN 98056) and 'Z 11637' (CN 98150) produce neither [1-9-NαC]-linusorb B2 (3) nor [1-9-NαC]-linusorb B3 (1). Mass spectrometry was used to identify novel compounds and elucidate their structure. NMR spectroscopy was used to corroborate structural information.

RESULTS: Experimental findings indicated that these accessions produce a novel orbitide, identified in three oxidation states having quasimolecular ion peaks at m/z 1072.6 (18), 1088.6 (19), and 1104.6 (20) [M + H]+ corresponding to molecular formulae C57H86N9O9S, C57H86N9O10S, and C57H86N9O11S, respectively. The structure of 19 was confirmed unequivocally as [1-9-NαC]-OLIPPFFLI. PCR amplification and sequencing of the gene coding for 18, using primers developed for 3 and 1, identified the putative linear precursor protein of 18 as being comprised of the first three amino acid residues of 3 (MLI), four conserved amino acid residues of 3 and/or 1 (PPFF), and the last two residues of 1 (LI).

CONCLUSION: Comparison of gene sequencing data revealed that a 117 base pair deletion had occurred that resulted in truncation of both 3 and 1 to produce a sequence encoding for the novel orbitide precursor of 18. This observation suggests that repeat units of flax orbitide genes are conserved and suggests a novel mechanism for evolution of orbitide gene diversity. Orbitides 19 and 20 contain MetO and MetO2, respectively, and are not directly encoded, but are products of post-translation modification of Met present in 18 ([1-9-NαC]-MLIPPFFLI).}, } @article {pmid29783945, year = {2018}, author = {Westreich, ST and Treiber, ML and Mills, DA and Korf, I and Lemay, DG}, title = {SAMSA2: a standalone metatranscriptome analysis pipeline.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {175}, pmid = {29783945}, issn = {1471-2105}, support = {T32-GM008799/NH/NIH HHS/United States ; T32 GM008799/GM/NIGMS NIH HHS/United States ; R01AT008759/NH/NIH HHS/United States ; R01 AT008759/AT/NCCIH NIH HHS/United States ; }, abstract = {BACKGROUND: Complex microbial communities are an area of growing interest in biology. Metatranscriptomics allows researchers to quantify microbial gene expression in an environmental sample via high-throughput sequencing. Metatranscriptomic experiments are computationally intensive because the experiments generate a large volume of sequence data and each sequence must be compared with reference sequences from thousands of organisms.

RESULTS: SAMSA2 is an upgrade to the original Simple Annotation of Metatranscriptomes by Sequence Analysis (SAMSA) pipeline that has been redesigned for standalone use on a supercomputing cluster. SAMSA2 is faster due to the use of the DIAMOND aligner, and more flexible and reproducible because it uses local databases. SAMSA2 is available with detailed documentation, and example input and output files along with examples of master scripts for full pipeline execution.

CONCLUSIONS: SAMSA2 is a rapid and efficient metatranscriptome pipeline for analyzing large RNA-seq datasets in a supercomputing cluster environment. SAMSA2 provides simplified output that can be examined directly or used for further analyses, and its reference databases may be upgraded, altered or customized to fit the needs of any experiment.}, } @article {pmid29783944, year = {2018}, author = {Rovadoscki, GA and Pertile, SFN and Alvarenga, AB and Cesar, ASM and Pértille, F and Petrini, J and Franzo, V and Soares, WVB and Morota, G and Spangler, ML and Pinto, LFB and Carvalho, GGP and Lanna, DPD and Coutinho, LL and Mourão, GB}, title = {Estimates of genomic heritability and genome-wide association study for fatty acids profile in Santa Inês sheep.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {375}, pmid = {29783944}, issn = {1471-2164}, support = {Proc 13/04504-3//Fapesp/ ; }, mesh = {Animals ; Fatty Acids/*metabolism ; *Genome-Wide Association Study ; *Genomics ; Multivariate Analysis ; *Quantitative Trait, Heritable ; Sheep/*genetics/*metabolism ; }, abstract = {BACKGROUND: Despite the health concerns and nutritional importance of fatty acids, there is a relative paucity of studies in the literature that report genetic or genomic parameters, especially in the case of sheep populations. To investigate the genetic architecture of fatty acid composition of sheep, we conducted genome-wide association studies (GWAS) and estimated genomic heritabilities for fatty acid profile in Longissimus dorsi muscle of 216 male sheep.

RESULTS: Genomic heritability estimates for fatty acid content ranged from 0.25 to 0.46, indicating that substantial genetic variation exists for the evaluated traits. Therefore, it is possible to alter fatty acid profiles through selection. Twenty-seven genomic regions of 10 adjacent SNPs associated with fatty acids composition were identified on chromosomes 1, 2, 3, 5, 8, 12, 14, 15, 16, 17, and 18, each explaining ≥0.30% of the additive genetic variance. Twenty-three genes supporting the understanding of genetic mechanisms of fat composition in sheep were identified in these regions, such as DGAT2, TRHDE, TPH2, ME1, C6, C7, UBE3D, PARP14, and MRPS30.

CONCLUSIONS: Estimates of genomic heritabilities and elucidating important genomic regions can contribute to a better understanding of the genetic control of fatty acid deposition and improve the selection strategies to enhance meat quality and health attributes.}, } @article {pmid29783941, year = {2018}, author = {Berthelier, J and Casse, N and Daccord, N and Jamilloux, V and Saint-Jean, B and Carrier, G}, title = {A transposable element annotation pipeline and expression analysis reveal potentially active elements in the microalga Tisochrysis lutea.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {378}, pmid = {29783941}, issn = {1471-2164}, support = {ANR-16-CE20-0016-01//DynAlgue/ ; }, mesh = {DNA Transposable Elements/*genetics ; Gene Expression Profiling/*methods ; Genomics ; Microalgae/*genetics ; Molecular Sequence Annotation/*methods ; }, abstract = {BACKGROUND: Transposable elements (TEs) are mobile DNA sequences known as drivers of genome evolution. Their impacts have been widely studied in animals, plants and insects, but little is known about them in microalgae. In a previous study, we compared the genetic polymorphisms between strains of the haptophyte microalga Tisochrysis lutea and suggested the involvement of active autonomous TEs in their genome evolution.

RESULTS: To identify potentially autonomous TEs, we designed a pipeline named PiRATE (Pipeline to Retrieve and Annotate Transposable Elements, download: https://doi.org/10.17882/51795), and conducted an accurate TE annotation on a new genome assembly of T. lutea. PiRATE is composed of detection, classification and annotation steps. Its detection step combines multiple, existing analysis packages representing all major approaches for TE detection and its classification step was optimized for microalgal genomes. The efficiency of the detection and classification steps was evaluated with data on the model species Arabidopsis thaliana. PiRATE detected 81% of the TE families of A. thaliana and correctly classified 75% of them. We applied PiRATE to T. lutea genomic data and established that its genome contains 15.89% Class I and 4.95% Class II TEs. In these, 3.79 and 17.05% correspond to potentially autonomous and non-autonomous TEs, respectively. Annotation data was combined with transcriptomic and proteomic data to identify potentially active autonomous TEs. We identified 17 expressed TE families and, among these, a TIR/Mariner and a TIR/hAT family were able to synthesize their transposase. Both these TE families were among the three highest expressed genes in a previous transcriptomic study and are composed of highly similar copies throughout the genome of T. lutea. This sum of evidence reveals that both these TE families could be capable of transposing or triggering the transposition of potential related MITE elements.

CONCLUSION: This manuscript provides an example of a de novo transposable element annotation of a non-model organism characterized by a fragmented genome assembly and belonging to a poorly studied phylum at genomic level. Integration of multi-omics data enabled the discovery of potential mobile TEs and opens the way for new discoveries on the role of these repeated elements in genomic evolution of microalgae.}, } @article {pmid29783940, year = {2018}, author = {Seifert, F and Thiemann, A and Schrag, TA and Rybka, D and Melchinger, AE and Frisch, M and Scholten, S}, title = {Small RNA-based prediction of hybrid performance in maize.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {371}, pmid = {29783940}, issn = {1471-2164}, support = {FR 1615/4-1//Deutsche Forschungsgemeinschaft/ ; ME 2260/5-1//Deutsche Forschungsgemeinschaft/ ; SCHO 764/6-1//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Breeding ; Gene Expression Profiling ; Genomics ; *Hybridization, Genetic ; Polymorphism, Single Nucleotide ; RNA, Messenger/genetics ; RNA, Small Untranslated/*genetics ; Zea mays/*genetics/growth & development ; }, abstract = {BACKGROUND: Small RNA (sRNA) sequences are known to have a broad impact on gene regulation by various mechanisms. Their performance for the prediction of hybrid traits has not yet been analyzed. Our objective was to analyze the relation of parental sRNA expression with the performance of their hybrids, to develop a sRNA-based prediction approach, and to compare it to more common SNP and mRNA transcript based predictions using a factorial mating scheme of a maize hybrid breeding program.

RESULTS: Correlation of genomic differences and messenger RNA (mRNA) or sRNA expression differences between parental lines with hybrid performance of their hybrids revealed that sRNAs showed an inverse relationship in contrast to the other two data types. We associated differences for SNPs, mRNA and sRNA expression between parental inbred lines with the performance of their hybrid combinations and developed two prediction approaches using distance measures based on associated markers. Cross-validations revealed parental differences in sRNA expression to be strong predictors for hybrid performance for grain yield in maize, comparable to genomic and mRNA data. The integration of both positively and negatively associated markers in the prediction approaches enhanced the prediction accurary. The associated sRNAs belong predominantly to the canonical size classes of 22- and 24-nt that show specific genomic mapping characteristics.

CONCLUSION: Expression profiles of sRNA are a promising alternative to SNPs or mRNA expression profiles for hybrid prediction, especially for plant species without reference genome or transcriptome information. The characteristics of the sRNAs we identified suggest that association studies based on breeding populations facilitate the identification of sRNAs involved in hybrid performance.}, } @article {pmid29783939, year = {2018}, author = {Moreira, GCM and Boschiero, C and Cesar, ASM and Reecy, JM and Godoy, TF and Trevisoli, PA and Cantão, ME and Ledur, MC and Ibelli, AMG and Peixoto, JO and Moura, ASAMT and Garrick, D and Coutinho, LL}, title = {A genome-wide association study reveals novel genomic regions and positional candidate genes for fat deposition in broiler chickens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {374}, pmid = {29783939}, issn = {1471-2164}, support = {2014/08704-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2014/21380-9//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2016/00569-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2015/00616-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 370620/2013-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Adipose Tissue/*metabolism ; Animals ; Chickens/*genetics/*metabolism ; *Genome-Wide Association Study ; *Genomics ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: Excess fat content in chickens has a negative impact on poultry production. The discovery of QTL associated with fat deposition in the carcass allows the identification of positional candidate genes (PCGs) that might regulate fat deposition and be useful for selection against excess fat content in chicken's carcass. This study aimed to estimate genomic heritability coefficients and to identify QTLs and PCGs for abdominal fat (ABF) and skin (SKIN) traits in a broiler chicken population, originated from the White Plymouth Rock and White Cornish breeds.

RESULTS: ABF and SKIN are moderately heritable traits in our broiler population with estimates ranging from 0.23 to 0.33. Using a high density SNP panel (355,027 informative SNPs), we detected nine unique QTLs that were associated with these fat traits. Among these, four QTL were novel, while five have been previously reported in the literature. Thirteen PCGs were identified that might regulate fat deposition in these QTL regions: JDP2, PLCG1, HNF4A, FITM2, ADIPOR1, PTPN11, MVK, APOA1, APOA4, APOA5, ENSGALG00000000477, ENSGALG00000000483, and ENSGALG00000005043. We used sequence information from founder animals to detect 4843 SNPs in the 13 PCGs. Among those, two were classified as potentially deleterious and two as high impact SNPs.

CONCLUSIONS: This study generated novel results that can contribute to a better understanding of fat deposition in chickens. The use of high density array of SNPs increases genome coverage and improves QTL resolution than would have been achieved with low density. The identified PCGs were involved in many biological processes that regulate lipid storage. The SNPs identified in the PCGs, especially those predicted as potentially deleterious and high impact, may affect fat deposition. Validation should be undertaken before using these SNPs for selection against carcass fat accumulation and to improve feed efficiency in broiler chicken production.}, } @article {pmid29783938, year = {2018}, author = {Panda, BB and Sekhar, S and Dash, SK and Behera, L and Shaw, BP}, title = {Biochemical and molecular characterisation of exogenous cytokinin application on grain filling in rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {89}, pmid = {29783938}, issn = {1471-2229}, support = {NO. SB/YS/LS-73/2013//Department of Biotechnology , Ministry of Science and Technology (IN)/ ; }, mesh = {Benzyl Compounds/pharmacology ; Cell Count ; Cytokinins/*pharmacology ; Edible Grain/*drug effects/growth & development/metabolism ; Endosperm/cytology/drug effects/growth & development/ultrastructure ; Flow Cytometry ; Oryza/*drug effects/growth & development/metabolism/ultrastructure ; Oxidoreductases/metabolism ; Purines/pharmacology ; Transcriptome ; }, abstract = {BACKGROUND: Poor filling of grains in the basal spikelets of large size panicles bearing numerous spikelets has been a major limitation in attempts to increase the rice production to feed the world's increasing population. Considering that biotechnological intervention could play important role in overcoming this limitation, the role of cytokinin in grain filling was investigated based on the information on cell proliferating potential of the hormone and reports of its high accumulation in immature seeds.

RESULTS: A comparative study considering two rice varieties differing in panicle compactness, lax-panicle Upahar and compact-panicle OR-1918, revealed significant difference in grain filling, cytokinin oxidase (CKX) activity and expression, and expression of cell cycle regulators and cytokinin signaling components between the basal and apical spikelets of OR-1918, but not of Upahar. Exogenous application of cytokinin (6-Benzylaminopurine, BAP) to OR-1918 improved grain filling significantly, and this was accompanied by a significant decrease in expression and activity of CKX, particularly in the basal spikelets where the activity of CKX was significantly higher than that in the apical spikelets. Cytokinin application also resulted in significant increase in expression of cell cycle regulators like cyclin dependent kinases and cyclins in the basal spikelets that might be facilitating cell division in the endosperm cells by promoting G1/S phase and G2/M phase transition leading to improvement in grain filling. Expression studies of type-A response regulator (RR) component of cytokinin signaling indicated possible role of OsRR3, OsRR4 and OsRR6 as repressors of CKX expression, much needed for an increased accumulation of CK in cells. Furthermore, the observed effect of BAP might not be solely because of it, but also because of induced synthesis of trans-zeatin (tZ) and N6-(Δ2-isopentenyl)adenine (iP), as reflected from accumulation of tZR (tZ riboside) and iPR (iP riboside), and significantly enhanced expression of an isopentenyl transferase (IPT) isoform.

CONCLUSION: The results suggested that seed-specific overexpression of OsRR4 and OsRR6, and more importantly of IPT9 could be an effective biotechnological intervention towards improving the CK level of the developing caryopses leading to enhanced grain filling in rice cultivars bearing large panicles with numerous spikelets, and thereby increasing their yield potential.}, } @article {pmid29783926, year = {2018}, author = {Crichton, G and Guo, Y and Pyysalo, S and Korhonen, A}, title = {Neural networks for link prediction in realistic biomedical graphs: a multi-dimensional evaluation of graph embedding-based approaches.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {176}, pmid = {29783926}, issn = {1471-2105}, support = {MR/M013049/1//Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Link prediction in biomedical graphs has several important applications including predicting Drug-Target Interactions (DTI), Protein-Protein Interaction (PPI) prediction and Literature-Based Discovery (LBD). It can be done using a classifier to output the probability of link formation between nodes. Recently several works have used neural networks to create node representations which allow rich inputs to neural classifiers. Preliminary works were done on this and report promising results. However they did not use realistic settings like time-slicing, evaluate performances with comprehensive metrics or explain when or why neural network methods outperform. We investigated how inputs from four node representation algorithms affect performance of a neural link predictor on random- and time-sliced biomedical graphs of real-world sizes (∼ 6 million edges) containing information relevant to DTI, PPI and LBD. We compared the performance of the neural link predictor to those of established baselines and report performance across five metrics.

RESULTS: In random- and time-sliced experiments when the neural network methods were able to learn good node representations and there was a negligible amount of disconnected nodes, those approaches outperformed the baselines. In the smallest graph (∼ 15,000 edges) and in larger graphs with approximately 14% disconnected nodes, baselines such as Common Neighbours proved a justifiable choice for link prediction. At low recall levels (∼ 0.3) the approaches were mostly equal, but at higher recall levels across all nodes and average performance at individual nodes, neural network approaches were superior. Analysis showed that neural network methods performed well on links between nodes with no previous common neighbours; potentially the most interesting links. Additionally, while neural network methods benefit from large amounts of data, they require considerable amounts of computational resources to utilise them.

CONCLUSIONS: Our results indicate that when there is enough data for the neural network methods to use and there are a negligible amount of disconnected nodes, those approaches outperform the baselines. At low recall levels the approaches are mostly equal but at higher recall levels and average performance at individual nodes, neural network approaches are superior. Performance at nodes without common neighbours which indicate more unexpected and perhaps more useful links account for this.}, } @article {pmid29783022, year = {2018}, author = {Liu, J and Zhang, S and Nagalingum, NS and Chiang, YC and Lindstrom, AJ and Gong, X}, title = {Phylogeny of the gymnosperm genus Cycas L. (Cycadaceae) as inferred from plastid and nuclear loci based on a large-scale sampling: Evolutionary relationships and taxonomical implications.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {87-97}, doi = {10.1016/j.ympev.2018.05.019}, pmid = {29783022}, issn = {1095-9513}, abstract = {The gymnosperm genus Cycas is the sole member of Cycadaceae, and is the largest genus of extant cycads. There are about 115 accepted Cycas species mainly distributed in the paleotropics. Based on morphology, the genus has been divided into six sections and eight subsections, but this taxonomy has not yet been tested in a molecular phylogenetic framework. Although the monophyly of Cycas is broadly accepted, the intrageneric relationships inferred from previous molecular phylogenetic analyses are unclear due to insufficient sampling or uninformative DNA sequence data. In this study, we reconstructed a phylogeny of Cycas using four chloroplast intergenic spacers and seven low-copy nuclear genes and sampling 90% of extant Cycas species. The maximum likelihood and Bayesian inference phylogenies suggest: (1) matrices of either concatenated cpDNA markers or of concatenated nDNA lack sufficient informative sites to resolve the phylogeny alone, however, the phylogeny from the combined cpDNA-nDNA dataset suggests the genus can be roughly divided into 13 clades and six sections that are in agreement with the current classification of the genus; (2) although with partial support, a clade combining sections Panzhihuaenses + Asiorientales is resolved as the earliest diverging branch; (3) section Stangerioides is not monophyletic because the species resolve as a grade; (4) section Indosinenses is not monophyletic as it includes Cycas macrocarpa and C. pranburiensis from section Cycas; (5) section Cycas is the most derived group and its subgroups correspond with geography.}, } @article {pmid29783021, year = {2018}, author = {Pinacho-Pinacho, CD and García-Varela, M and Sereno-Uribe, AL and Pérez-Ponce de León, G}, title = {A hyper-diverse genus of acanthocephalans revealed by tree-based and non-tree-based species delimitation methods: Ten cryptic species of Neoechinorhynchus in Middle American freshwater fishes.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {30-45}, doi = {10.1016/j.ympev.2018.05.023}, pmid = {29783021}, issn = {1095-9513}, abstract = {The genus Neoechinorhynchus represents a hyper-diverse group of acanthocephalans, parasites of fresh and brackish water fish and freshwater turtles, with approximately 116 species described worldwide. Forty-nine species have been recorded in the Americas, nine of them in Middle America. Even though species delimitation methods using DNA sequences have been rarely used for parasitic helminths, the genetic library for species of Neoechinorhynchus has grown in the past few years, enhancing the possibility of using these methods for inferring evolutionary relationships and for establishing more robust species boundaries. In this study, we used non-tree-based and tree-based methods through a coalescent approach to explore the species limits of specimens of Neoechinorhynchus collected in 57 localities across Middle America. We sequenced a large number of individuals to build a comprehensive dataset for three genes: the mitochondrial cytochrome c oxidase subunit I (352 individuals), the internal transcribed spacers (330 individuals), and the D2 + D3 domains of the large subunit (278 individuals). Several species delimitation methods were implemented, i.e., Automatic Barcode Gap Discovery (ABGD), General Mixed Yule-Coalescent Model (GMYC), Bayesian species delimitation (BPP) and species tree (∗BEAST). Additionally, we conducted a detailed morphological study of the diagnostic traits associated with the proboscis of 184 males and 169 females. Overall, our analyses allowed us to validate nine nominal species of Neoechinorhynchus and to identify 10 additional genetic lineages herein regarded as candidate species. This unexpected genetic diversity and the lack of reliable morphological traits show that the genus Neoechinorhynchus includes a group of cryptic species, at least in Middle America.}, } @article {pmid29782817, year = {2018}, author = {Fernandes, VFL and Macaspac, C and Lu, L and Yoshizawa, M}, title = {Evolution of the developmental plasticity and a coupling between left mechanosensory neuromasts and an adaptive foraging behavior.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {262-271}, doi = {10.1016/j.ydbio.2018.05.012}, pmid = {29782817}, issn = {1095-564X}, mesh = {Animals ; *Biological Evolution ; Characiformes/*embryology ; Endothelins/metabolism ; Feeding Behavior/*physiology ; Fish Proteins/agonists/metabolism ; Mechanotransduction, Cellular/*physiology ; Osteogenesis/*physiology ; Receptors, Endothelin/agonists/metabolism ; Skull/*embryology ; }, abstract = {Many animal species exhibit laterality in sensation and behavioral responses, namely, the preference for using either the left or right side of the sensory system. For example, some fish use their left eye when observing social stimuli, whereas they use their right eye to observe novel objects. However, it is largely unknown whether such laterality in sensory-behavior coupling evolves during rapid adaptation processes. Here, in the Mexican tetra, Astyanax mexicanus, we investigate the laterality in the relationship between an evolved adaptive behavior, vibration attraction behavior (VAB), and its main sensors, mechanosensory neuromasts. A. mexicanus has a surface-dwelling form and cave-dwelling forms (cavefish), whereby a surface fish ancestor colonized the new environment of a cave, eventually evolving cave-type morphologies such as increased numbers of neuromasts at the cranium. These neuromasts are known to regulate VAB, and it is known that, in teleosts, the budding (increasing) process of neuromasts is accompanied with dermal bone formation. This bone formation is largely regulated by endothelin signaling. To assess the evolutionary relationship between bone formation, neuromast budding, and VAB, we treated 1-3 month old juvenile fish with endothelin receptor antagonists. This treatment significantly increased cranial neuromasts in both surface and cavefish, and the effect was significantly more pronounced in cavefish. Antagonist treatment also increased the size of dermal bones in cavefish, but neuromast enhancement was observed earlier than dermal bone formation, suggesting that endothelin signaling may independently regulate neuromast development and bone formation. In addition, although we did not detect a major change in VAB level under this antagonist treatment, cavefish did show a positive correlation of VAB with the number of neuromasts on their left side but not their right. This laterality in correlation was observed when VAB emerged during cavefish development, but it was not seen in surface fish under any conditions tested, suggesting this laterality emerged through an evolutionary process. Above all, cavefish showed higher developmental plasticity in neuromast number and bone formation, and they showed an asymmetric correlation between the number of left-right neuromasts and VAB.}, } @article {pmid29781802, year = {2018}, author = {Lee, DW and Lee, H and Kwon, BO and Khim, JS and Yim, UH and Park, H and Park, B and Choi, IG and Kim, BS and Kim, JJ}, title = {Zobellella maritima sp. nov., a polycyclic aromatic hydrocarbon-degrading bacterium, isolated from beach sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2279-2284}, doi = {10.1099/ijsem.0.002825}, pmid = {29781802}, issn = {1466-5034}, mesh = {Aeromonadaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Polycyclic Aromatic Hydrocarbons/*metabolism ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; }, abstract = {A novel Gram-stain-negative, motile, rod-shaped bacterium, designated strain 102-Py4T, was isolated from Sinduri beach sediment in Taean, Republic of Korea. Cells were aerobic, oxidase-positive and catalase-positive. The isolate grew optimally with 1-3 % (w/v) NaCl, but NaCl is not an absolute requirement for growth. 16S rRNA gene sequence analysis revealed that strain 102-Py4T clustered together with Zobellella aerophila and fell within the clade formed by recognized species of the genus Zobellella. Its closest phylogenetic neighbours were Z. aerophila JC2671T (98.1 % 16S rRNA gene sequence similarity), Zobellella denitrificans ZD1T (96.4 %) and Zobellella taiwanensis ZT1T (96.0 %). The major fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C12 : 0, summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The polar lipids were phosphatidylethanolamine, phosphatidylglycerol and two unidentified amino lipids. The DNA G+C content was 62.1 mol%. The DNA-DNA relatedness value between strain 102-Py4T and Z. aerophila JC2671T was 12.4±1.3 %. The phenotypic properties of 102-Py4T demonstrated that this strain could be distinguished from other Zobellella species. On the basis of the data presented, strain 102-Py4T (=KCTC 62272T=JCM 32359T=DSM 106043T) is considered to represent a novel species of the genus Zobellella, for which the name Zobellella maritima sp. nov. is proposed.}, } @article {pmid29781801, year = {2018}, author = {Sorokin, DY and Merkel, AY and Abbas, B and Makarova, KS and Rijpstra, WIC and Koenen, M and Sinninghe Damsté, JS and Galinski, EA and Koonin, EV and van Loosdrecht, MCM}, title = {Methanonatronarchaeum thermophilum gen. nov., sp. nov. and 'Candidatus Methanohalarchaeum thermophilum', extremely halo(natrono)philic methyl-reducing methanogens from hypersaline lakes comprising a new euryarchaeal class Methanonatronarchaeia classis nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2199-2208}, doi = {10.1099/ijsem.0.002810}, pmid = {29781801}, issn = {1466-5034}, mesh = {Base Composition ; California ; Chemoautotrophic Growth ; Egypt ; Euryarchaeota/*classification/genetics/isolation & purification ; Lakes/*microbiology ; Methane/*metabolism ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Russia ; *Salinity ; Sequence Analysis, DNA ; }, abstract = {Methanogenic enrichments from hypersaline lakes at moderate thermophilic conditions have resulted in the cultivation of an unknown deep lineage of euryarchaeota related to the class Halobacteria. Eleven soda lake isolates and three salt lake enrichment cultures were methyl-reducing methanogens that utilize C1 methylated compounds as electron acceptors and H2 or formate as electron donors, but they were unable to grow on either substrates alone or to form methane from acetate. They are extreme halophiles, growing optimally at 4 M total Na+ and the first representatives of methanogens employing the 'salt-in' osmoprotective mechanism. The salt lake subgroup is neutrophilic, whereas the soda lake isolates are obligate alkaliphiles, with an optimum around pH 9.5. Both grow optimally at 50 °C. The genetic diversity inside the two subgroups is very low, indicating that the soda and salt lake clusters consist of a single genetic species each. The phylogenetic distance between the two subgroups is in the range of distant genera, whereas the distance to other euryarchaea is below 83 % identity of the 16S rRNA gene. These isolates and enriched methanogens, together with closely related environmental clones from hypersaline habitats (the SA1 group), form a novel class-level clade in the phylum Euryarchaeota. On the basis of distinct phenotypic and genetic properties, the soda lake isolates are classified into a new genus and species, Methanonatronarchaeum thermophilum, with the type strain AMET1T (DSM 28684T=NBRC 110805T=UNIQEM U982T), and the salt lake methanogens into a candidate genus and species 'Candidatus Methanohalarchaeum thermophilum'. These organisms are proposed to form novel family, order and class Methanonatronarchaeaceae fam. nov., Methanonatronarchaeales ord. nov. and Methanonatronarchaeia classis nov., within the phylum Euryarchaeota.}, } @article {pmid29781798, year = {2018}, author = {Zhuang, L and Lin, B and Qin, F and Luo, L}, title = {Zhouia spongiae sp. nov., isolated from a marine sponge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2194-2198}, doi = {10.1099/ijsem.0.002808}, pmid = {29781798}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Porifera/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A taxonomic study was carried out on strain HN-Y44T, which was isolated from sponge collected from Yangpu Bay, Hainan, China. Cells of strain HN-Y44T were Gram-stain-negative, non-motile, rod-shaped, yellow-pigmented and grew at 10-40 °C (optimum, 28 °C), at pH 6-10 (optimum, 7-8) and in 0-8 % (w/v) NaCl (optimum, 2-5 %). This isolate was positive for nitrate reduction, denitrification, oxidase, catalase and aesculin hydrolysis, but negative for indole production and urease. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain HN-Y44T belongs to the genus Zhouia and is clearly distinct from the other described species of this genus, Zhouia amylolytica, with a 16S rRNA gene sequence similarity of 96.85 %. The dominant fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The major polar lipids comprised phosphatidylethanolamine, four unidentified aminolipids, four unidentified phospholipids and one unidentified lipid. The respiratory lipoquinone was identified as MK-6. The G+C content of the genomic DNA was 32.9 mol%. On the basis of the phenotypic and phylogenetic data, strain HN-Y44T represents a novel species of the genus Zhouia, for which the name Zhouia spongiae sp. nov. is proposed, with the type strain HN-Y44T (=MCCC 1K03329T=LMG 30460T).}, } @article {pmid29781796, year = {2018}, author = {Amoikon, TLS and Grondin, C and Djéni, TN and Jacques, N and Casaregola, S}, title = {Starmerella reginensis f.a., sp. nov. and Starmerella kourouensis f.a., sp. nov., isolated from flowers in French Guiana.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2299-2305}, doi = {10.1099/ijsem.0.002829}, pmid = {29781796}, issn = {1466-5034}, mesh = {DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Flowers/*microbiology ; French Guiana ; Genes, Fungal ; Mycological Typing Techniques ; Peptide Elongation Factor 1/genetics ; *Phylogeny ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {Analysis of yeasts isolated from various biotopes in French Guiana led to the identification of two strains isolated from flowers and designated CLIB 1634T and CLIB 1707T. Comparison of the D1/D2 domain of the large subunit (LSU D1/D2) rRNA gene sequences of CLIB 1634T and CLIB 1707T to those in the GenBank database revealed that these strains belong to the Starmerella clade. Strain CLIB 1634T was shown to diverge from the closely related Starmerella apicola type strain CBS 2868T with a sequence divergence of 1.34 and 1.30 %, in the LSU D1/D2 rRNA gene and internal transcribed spacer (ITS) sequences respectively. Strain CLIB 1634T and Candida apicola CBS 2868T diverged by 3.81 and 14.96 % at the level of the protein-coding gene partial sequences EF-1α and RPB2, respectively. CLIB 1707T was found to have sequence divergence of 3.88 and 9.16 % in the LSU D1/D2 rRNA gene and ITS, respectively, from that of the most closely related species Starmerella ratchasimensis type strain CBS 10611T. The species Starmerella reginensis f.a., sp. nov. and Starmerella kourouensis f.a., sp. nov. are proposed to accommodate strains CLIB 1634T (=CBS 15247T) and CLIB 1707T (=CBS 15257T), respectively.}, } @article {pmid29781795, year = {2018}, author = {Wang, XQ and Li, CM and Dunlap, CA and Rooney, AP and Du, ZJ}, title = {Marinicella sediminis sp. nov., isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2335-2339}, doi = {10.1099/ijsem.0.002839}, pmid = {29781795}, issn = {1466-5034}, mesh = {Alcanivoraceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {A novel heterotrophic, Gram-stain-negative, aerobic, rod-shaped, pale yellow, non-motile and non-spore-forming bacterium, designated strain F2T, was isolated from marine sediment collected from the Weihai coast, Shandong Province, PR China. Optimal growth occurred at 33 °C (range, 10-37 °C), with 3.0-4.0 % (w/v) NaCl (1.0-8.0 %) and at pH 7.5-8.0 (pH 6.5-9.0). Q-8 was the sole respiratory quinone. The major polar lipids of strain F2T were phosphatidylmonomethylethanolamine, phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids and two unidentified polar lipids. The major cellular fatty acid in strain F2T was iso-C15 : 0. The genomic DNA G+C content of the strain was 48.1 mol%. Phylogenetic analysis based on 16S rRNA gene sequencing revealed that strain F2T is most closely related to Marinicella litoralis JCM 16154T (97.5 %) and Marinicella pacifica sw153T (96.0 %). Based on the results of our polyphasic analysis, we conclude that strain F2T represents a novel species of the genus Marinicella, for which the name Marinicella sediminis sp. nov. is proposed. The type strain of the new species is F2T (=KCTC 42953T=MCCC 1H00149T).}, } @article {pmid29781132, year = {2018}, author = {Yue, L and Yu, HF and Yang, ZQ and Tian, XC and Zheng, LW and Guo, B}, title = {Egr2 mediates the differentiation of mouse uterine stromal cells responsiveness to HB-EGF during decidualization.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {4}, pages = {215-224}, doi = {10.1002/jez.b.22807}, pmid = {29781132}, issn = {1552-5015}, abstract = {Although Egr2 is involved in regulating the folliculogenesis and ovulation, there is almost no data describing its physiological function in embryo implantation and decidualization. Here, we showed that Egr2 mRNA was distinctly accumulated in subluminal stromal cells around implanting blastocyst on day 5 of pregnancy as well as in estrogen-activated implantation uterus. Estrogen induced the expression of Egr2 in uterine epithelia. Elevated expression of Egr2 mRNA was also observed in the decidual cells. Silencing of Egr2 by specific siRNA weakened the proliferation of uterine stromal cells and reduced the expression of Ccnd1, Ccnd3, Cdk4, and Cdk6. Furthermore, Egr2 advanced the expression of Prl8a2, Prl3c1, and Pgr, the well-established differentiation markers for decidualization. Administration of exogenous recombinant heparin-binding EGF-like growth factor (rHB-EGF) to uterine stromal cells resulted in an increase in the level of Egr2 mRNA. Moreover, siRNA-mediated attenuation of Egr2 impeded the stimulation of HB-EGF on stromal cell differentiation. Knockdown of Egr2 led to a reduction in the expression of Cox-2, mPGES-1, Vegf, Trp53, and Mmp2. Further analysis found that Egr2 may serve as an intermediate to mediate the regulation of HB-EGF on Cox-2, mPGES-1, Vegf, Trp53, Mmp2, and Ccnd3. Collectively, Egr2 may play an important role during embryo implantation and decidualization.}, } @article {pmid29779985, year = {2018}, author = {Smith, ML and Styczynski, MP}, title = {Systems Biology-Based Investigation of Host-Plasmodium Interactions.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {617-632}, doi = {10.1016/j.pt.2018.04.003}, pmid = {29779985}, issn = {1471-5007}, support = {HHSN272201200031C/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Host-Parasite Interactions/*physiology ; Humans ; Malaria/*parasitology ; Plasmodium/*physiology ; *Systems Biology ; }, abstract = {Malaria is a serious, complex disease caused by parasites of the genus Plasmodium. Plasmodium parasites affect multiple tissues as they evade immune responses, replicate, sexually reproduce, and transmit between vertebrate and invertebrate hosts. The explosion of omics technologies has enabled large-scale collection of Plasmodium infection data, revealing systems-scale patterns, mechanisms of pathogenesis, and the ways that host and pathogen affect each other. Here, we provide an overview of recent efforts using systems biology approaches to study host-Plasmodium interactions and the biological themes that have emerged from these efforts. We discuss some of the challenges in using systems biology for this goal, key research efforts needed to address those issues, and promising future malaria applications of systems biology.}, } @article {pmid29779797, year = {2018}, author = {Binney, N}, title = {The function of the heart is historically contingent.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {68-69}, number = {}, pages = {42-55}, doi = {10.1016/j.shpsc.2018.05.002}, pmid = {29779797}, issn = {1879-2499}, mesh = {Heart Failure/classification/*history/physiopathology ; History, 19th Century ; History, 20th Century ; Humans ; *Terminology as Topic ; United Kingdom ; United States ; }, abstract = {Some philosophers of medicine argue that there are objective facts about the biological function of organs, and that these facts are used to objectively define diseases. The function of the heart is taken to be particularly obvious and well established. Contrary to this, I argue that the function of the heart is not fixed by nature, but rather that it is historically contingent. The disease heart failure results from the dysfunction of the heart. In opposition to the common-sense intuitions of philosophers, medics do not define heart failure simply as a reduced cardiac output, and up to half of patients with heart failure have a normal cardiac output. The present day medical definition of heart failure is thus counter-intuitive. In the early twentieth century, however, medics did define heart failure as a reduced cardiac output. This view was opposed in the 1930s, when a similar definition of heart failure to the one used today was put forward. I look closely at this historical episode, in order to explore the reasons for this development. I use this history to argue that present day knowledge of heart failure is not the inevitable result of careful observation of patients, but rather is historically contingent.}, } @article {pmid29779686, year = {2018}, author = {Kostopoulos, DS and Guy, F and Kynigopoulou, Z and Koufos, GD and Valentin, X and Merceron, G}, title = {A 2Ma old baboon-like monkey from Northern Greece and new evidence to support the Paradolichopithecus - Procynocephalus synonymy (Primates: Cercopithecidae).}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {178-192}, doi = {10.1016/j.jhevol.2018.02.012}, pmid = {29779686}, issn = {1095-8606}, abstract = {A new fossil cranium of a large papionin monkey from the Lower Pleistocene site of Dafnero-3 in Western Macedonia, Greece, is described by means of outer and inner morphological and metric traits using high-resolution micro-computed tomography. Comparisons with modern cercopithecids and contemporaneous Eurasian fossil taxa suggest that the new cranium could equally be ascribed to either the Eurasian Paradolichopithecus or to the East Asian Procynocephalus. The combination of the available direct and indirect fossil evidence, including the new cranium from Dafnero, revives an earlier hypothesis that considers these two sparsely documented genera as synonyms. The timing and possible causes of the rise and demise of Paradolichopithecus - Procynocephalus are discussed.}, } @article {pmid29779605, year = {2018}, author = {Redpath, SM and Keane, A and Andrén, H and Baynham-Herd, Z and Bunnefeld, N and Duthie, AB and Frank, J and Garcia, CA and Månsson, J and Nilsson, L and Pollard, CRJ and Rakotonarivo, OS and Salk, CF and Travers, H}, title = {Games as Tools to Address Conservation Conflicts.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {415-426}, doi = {10.1016/j.tree.2018.03.005}, pmid = {29779605}, issn = {1872-8383}, mesh = {*Conflict (Psychology) ; Conservation of Natural Resources/*methods ; *Game Theory ; *Games, Experimental ; Role Playing ; }, abstract = {Conservation conflicts represent complex multilayered problems that are challenging to study. We explore the utility of theoretical, experimental, and constructivist approaches to games to help to understand and manage these challenges. We show how these approaches can help to develop theory, understand patterns in conflict, and highlight potentially effective management solutions. The choice of approach should be guided by the research question and by whether the focus is on testing hypotheses, predicting behaviour, or engaging stakeholders. Games provide an exciting opportunity to help to unravel the complexity in conflicts, while researchers need an awareness of the limitations and ethical constraints involved. Given the opportunities, this field will benefit from greater investment and development.}, } @article {pmid29778801, year = {2018}, author = {Parfejevs, V and Antunes, AT and Sommer, L}, title = {Injury and stress responses of adult neural crest-derived cells.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.05.011}, pmid = {29778801}, issn = {1095-564X}, abstract = {Multipotent neural crest cells can self-renew and give rise to a plethora of neural and non-neural cell types in the vertebrate embryo. Intriguingly, cells reminiscent of such neural crest stem cells (NCSCs) have also been isolated from various postnatal and adult neural crest (NC)-derived structures. However, it has been debated whether NCSC-like cells in the adult correspond to 'in vitro artefacts' emerging upon isolation or fulfil a physiological role in vivo. Here, we discuss recent findings indicating that in different adult NC derivatives, injury or stress responses induce a NCSC-like state, presumably by reprogramming differentiated cells such as Schwann cells. Thereby, injury or stress appear to endow NC-derived cells with the capacity to generate new cell types during the repair process; in addition, injury can activate a repair program in adult NC-derived cells, which promotes tissue repair or regeneration by paracrine signalling. Thus, there is increasing evidence that NCSC-like cells in NC derivatives represent an in vivo state implicated in distinct physiological functions in the adult organism.}, } @article {pmid29778724, year = {2018}, author = {Ortiz, D and Francke, OF and Bond, JE}, title = {A tangle of forms and phylogeny: Extensive morphological homoplasy and molecular clock heterogeneity in Bonnetina and related tarantulas.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {55-73}, doi = {10.1016/j.ympev.2018.05.013}, pmid = {29778724}, issn = {1095-9513}, abstract = {Tarantula spider systematics has long been considered problematic. Species diagnosis and phylogenetic hypotheses have historically relied on morphological features, which are known to be relatively conserved and/or highly homoplastic across the family. Morphology-based attempts to clarify the phylogeny of the highly diverse New World Theraphosinae, have only been moderately successful, and the time-frame of tarantulas' evolution is nearly terra incognita. Here we present a molecular phylogenetic analysis of the Theraphosinae genus Bonnetina and related lineages, employing one mitochondrial (COI) and five nuclear (ITS1, EF1G, MID1IP1, MRPL44, and I3568) loci. We also perform ancestral state reconstruction of a newly formulated morphological data matrix. Our analysis includes 47 species placed in 17 genera and other undetermined lineages. We obtained well resolved and supported topologies. COI and EF1G substitution rates were much lower than the values generally accepted for mygalomorph evolution, with substantial rate heterogeneity among lineages. The origin of Theraphosinae was dated during the Late Cretaceous, followed by rapid diversification into the three recently proposed Theraphosinae tribes. North and Central American Hapalopini (including Bonnetina) form a monophyletic group that likely originated during the Oligocene to a dispersing ancestor from the then isolated South America. A clade that includes all but one Bonnetina species is estimated to have originated in the early Miocene and is the sister group of two morphologically divergent undescribed species. Morphological homoplasy is extensive across the tree. The two features that diagnose Bonnetina are homoplastic, but in combination still define the genus. Finally, we establish three groups of species within Bonnetina. Our results challenge the reliability of morphological characters for phylogenetic reconstruction in Theraphosinae, and indicate caution when interpreting Theraphosidae supra-specific classification in absence of a solid phylogenetic framework. They also question the dependability of universal substitution rates of COI and EF1G to calibrate phylogenetic analyses across Mygalomorphae.}, } @article {pmid29778723, year = {2018}, author = {Li, F and Li, S}, title = {Paleocene-Eocene and Plio-Pleistocene sea-level changes as "species pumps" in Southeast Asia: Evidence from Althepus spiders.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {545-555}, doi = {10.1016/j.ympev.2018.05.014}, pmid = {29778723}, issn = {1095-9513}, mesh = {Animals ; Asia, Southeastern ; *Biodiversity ; Biological Evolution ; Geological Phenomena ; Oceans and Seas ; Phylogeny ; Spiders/*classification/genetics ; }, abstract = {Sea-level change has been viewed as a primary driver in the formation of biodiversity. Early studies confirmed that Plio-Pleistocene sea-level changes led to the isolation and subsequent genetic differentiation of Southeast (SE) Asian organisms over short geological timescales. However, long-time consequences of sea-level fluctuations remain unclear. Herein, we analyze the evolutionary history of Althepus (spiders) whose distribution encompasses Indo-Burma and the Sunda shelf islands to understand how sea-level changes over shallow and deep timescales effected their history. Our integrative analyses, including phylogeny, divergence times, ancestral area reconstruction and diversification dynamics, reveal an intricate pattern of diversification, probably triggered by sea-level fluctuations during the Paleocene-Eocene and Plio-Pleistocene. The timing of one early divergence between the Indo-Burmese and Sundaic species coincides with late Paleocene and early Eocene high global sea levels, which induced the formation of inland seaways in the Thai-Malay Peninsula. Subsequent lowered sea levels could have provided a land bridge for its dispersal colonization across the Isthmus of Kra. Analyses suggest that Plio-Pleistocene sea-level rises contributed to recent divergence of many species. Thus, our findings cannot reject the hypothesis that sea-level changes during the Paleocene-Eocene and Plio-Pleistocene played a major role in generating biodiversity in SE Asia; sea-level changes can act as "species pumps".}, } @article {pmid29778722, year = {2018}, author = {Heckenhauer, J and Samuel, R and Ashton, PS and Abu Salim, K and Paun, O}, title = {Phylogenomics resolves evolutionary relationships and provides insights into floral evolution in the tribe Shoreeae (Dipterocarpaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {1-13}, doi = {10.1016/j.ympev.2018.05.010}, pmid = {29778722}, issn = {1095-9513}, abstract = {A supra-annual, community-level synchronous flowering prevails in several parts of the tropical forests of Southeast Asia and its evolution has been hypothesized to be linked to pollinator shifts. The aseasonal Southeast Asian lowland rainforests are dominated by Dipterocarpaceae, which exhibit great floral diversity, a range of pollination syndromes and include species with annual and supra-annual gregarious flowering. Phylogenetic relationships within this family are still unclear, especially in the tribe Shoreeae. Here, we develop a pipeline to maximize recovery of genome-wide SNPs from restriction-site associated DNA sequencing (RADseq) in non-model organisms across wide phylogenetic scales. We then infer phylogenomic relationships in the tribe Shoreeae using both traditional and coalescent analyses. The phylogenetic trees obtained with these methods are congruent to each other and highly resolved. They allow reconstructing the evolutionary patterns of floral traits (number of stamens, anther structure and anther/appendage size) in the group. Our inferences indicate that species with many stamens, but smaller, globose anthers and longer appendages and have evolved multiple times from species with fewer stamens, but larger, oblong anthers and shorter appendages. This could have happened in parallel to iterative shifts in pollinators across the uncovered phylogeny from larger, longer generation to smaller, shorter-generation insects that can quickly build up the necessary population sizes during mass flowering episodes.}, } @article {pmid29778721, year = {2018}, author = {Tessler, M and de Carle, D and Voiklis, ML and Gresham, OA and Neumann, JS and Cios, S and Siddall, ME}, title = {Worms that suck: Phylogenetic analysis of Hirudinea solidifies the position of Acanthobdellida and necessitates the dissolution of Rhynchobdellida.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {129-134}, doi = {10.1016/j.ympev.2018.05.001}, pmid = {29778721}, issn = {1095-9513}, abstract = {Annelids possessing a posterior sucker and a fixed number of somites - most famously leeches (Hirudinida), but also crayfish worms (Branchiobdellida) and salmonid parasites (Acanthobdellida) - form a clade; however, determining the relationships between these orders has proven challenging. Here, we compile the largest molecular phylogenetic dataset yet analysed for these groups, including new sequences for key taxa. We find robust model-based support for a clade formed by Hirudinida and Acanthobdellida, contrasting the largest prior studies. We determine that conflicting prior studies included contaminant sequences for Acanthobdella peledina. In addition to this broad-scale comparison, the size of our dataset grants us invaluable insight into the internal relationships of leeches and crayfish worms. Of particular importance, a largely marine clade of leeches (Piscicolidae and Ozobranchidae) is recovered as sister to all remaining Hirudinida. This necessitates the dissolution of the paraphyletic suborder Rhynchobdellida into two new suborders (Oceanobdelliformes and Glossiphoniiformes). Likewise, we decompose Arhynchobdellida into its respective suborders: Hirudiniformes, Erpobdelliformes, and the new, monotypic, Americobdelliformes.}, } @article {pmid29778270, year = {2018}, author = {Alvergne, A and Högqvist Tabor, V}, title = {Is Female Health Cyclical? Evolutionary Perspectives on Menstruation.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {399-414}, doi = {10.1016/j.tree.2018.03.006}, pmid = {29778270}, issn = {1872-8383}, mesh = {Adaptive Immunity/immunology ; Animals ; *Biological Evolution ; Female ; *Host-Pathogen Interactions ; Humans ; Mammals/immunology/*physiology ; Menstrual Cycle/immunology/*physiology ; *Social Behavior ; }, abstract = {Why do some females menstruate at all? Answering this question has implications for understanding the tight links between reproductive function and organismal immunity. Here we build on the growing evidence that menstruation is the byproduct of a 'choosy uterus' to: (i) make the theoretical case for the idea that female immunity is cyclical in menstruating species, (ii) evaluate the evidence for the menstrual modulation of immunity and health in humans, and (iii) speculate on the implications of cyclical female health for female behaviour, male immunity, and host-pathogen interactions. We argue that an understanding of females' evolved reproductive system is foundational for both tackling the future challenges of the global women's health agenda and predicting eco-evolutionary dynamics in cyclically reproducing species.}, } @article {pmid29778246, year = {2018}, author = {Li, F and Bae, CJ and Ramsey, CB and Chen, F and Gao, X}, title = {Re-dating Zhoukoudian Upper Cave, northern China and its regional significance.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {170-177}, doi = {10.1016/j.jhevol.2018.02.011}, pmid = {29778246}, issn = {1095-8606}, abstract = {Due to the presence of multiple partial modern human skeletons thought to have been interred along with a diversity of evidence of symbolic behavior, Zhoukoudian Upper Cave (ZKD UC; formally "Choukoutien") from northern China has long been a critical site for understanding Late Quaternary human evolution and particularly the role eastern Asia played. Unfortunately, uncertainty regarding ZKD UC's chronology has long hindered determination of its importance in the debate over modern human origins. This situation has been particularly problematic because dates from the primary archaeological layers of ZKD UC have ranged from the Late Pleistocene to the Early Holocene (∼34-10 ka), with clearly different implications depending on which age is used. Here, we present a new set of accelerator mass spectrometry radiocarbon dating results from ZKD UC. Based on this new set of dates and further re-evaluations of the previous dating analyses, archaeological materials, published excavation reports and stratigraphy, we conclude that the ZKD UC archaeological layers minimally date to 35.1-33.5 ka. Given the similarities between the human fossils and archaeology between ZKD UC and western Eurasia, it is likely that the ZKD UC human foragers were part of dispersal events across northern Eurasia toward Siberia and eventually reaching into northern China.}, } @article {pmid29777837, year = {2018}, author = {Kropinski, AM}, title = {Bacteriophage research - What we have learnt and what still needs to be addressed.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {481-487}, doi = {10.1016/j.resmic.2018.05.002}, pmid = {29777837}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/administration & dosage/adverse effects/history ; *Bacteriophages/classification ; Classification ; Computational Biology/history ; Genomics/history ; History, 20th Century ; History, 21st Century ; Phage Therapy/history ; Research/*history ; Research Design ; }, abstract = {Research on bacteriophages has significantly enhanced our understanding of molecular biology, the genomes of prokaryotic cells, and viral ecology. Phages and lysins offer a viable alternative to the declining utility of antibiotics in this post-antibiotic era. They also provide ideal teaching tools for genomics and bioinformatics. This article touches on the first 100 years of phage research with the author commenting on what he thinks are the highlights, and what needs to be addressed.}, } @article {pmid29777836, year = {2018}, author = {Hoyle, N and Zhvaniya, P and Balarjishvili, N and Bolkvadze, D and Nadareishvili, L and Nizharadze, D and Wittmann, J and Rohde, C and Kutateladze, M}, title = {Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: a case report.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {540-542}, doi = {10.1016/j.resmic.2018.05.001}, pmid = {29777836}, issn = {1769-7123}, mesh = {Achromobacter denitrificans/*drug effects ; Adolescent ; Anti-Bacterial Agents/*pharmacology ; Cystic Fibrosis/*complications/microbiology/therapy ; Drug Resistance, Bacterial ; Female ; Gram-Negative Bacterial Infections/*therapy ; Humans ; Lung/drug effects/microbiology ; *Phage Therapy ; Pneumonia, Bacterial/*therapy ; }, abstract = {Respiratory infections can lead to serious complications in CF patients, especially when infected with antibiotic resistant bacteria. Alternative treatments for these infections are being sought out to help address this problem. We present a clinical case of a cystic fibrosis (CF) patient, with multi-drug resistant (MDR) Achromobacter xylosoxidans chronic lung infection who was successfully managed with bacteriophage therapy.}, } @article {pmid29777835, year = {2018}, author = {Gelman, D and Beyth, S and Lerer, V and Adler, K and Poradosu-Cohen, R and Coppenhagen-Glazer, S and Hazan, R}, title = {Combined bacteriophages and antibiotics as an efficient therapy against VRE Enterococcus faecalis in a mouse model.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {531-539}, doi = {10.1016/j.resmic.2018.04.008}, pmid = {29777835}, issn = {1769-7123}, mesh = {Animals ; Anti-Bacterial Agents/administration & dosage/*therapeutic use ; Bacteriophages/*physiology ; Disease Models, Animal ; Drug Therapy, Combination/methods ; Enterococcus faecalis/*drug effects/growth & development ; Female ; Gastrointestinal Microbiome/drug effects ; Gram-Positive Bacterial Infections/*therapy ; Mice ; Peritonitis/microbiology/therapy ; Phage Therapy/adverse effects/*methods ; Stem Cells ; }, abstract = {Clinical applications of bacteriophage therapy have been recently gathering significant attention worldwide, used mostly as rescue therapy in cases of near-fatal antibiotic failure. Thus, clinically relevant in-vivo models presenting both short- and long-term implications of phage therapy given as rescue treatment for fulminant infections are of highest importance. In this study, a cocktail consisting of two lytic bacteriophages was used to evaluate the therapeutic efficacy of phage therapy as a rescue treatment for severe septic peritonitis in a mouse model. We established that a single injection of the bacteriophage cocktail was sufficient to completely reverse a 100% mortality trend caused by Vancomycin-Resistant Enterococcus faecalis, with significant improvement in both the clinical state and laboratory test results, and without harmful effects on the microbiome. The combination of bacteriophages with a suboptimal antibiotic regimen imparts an additional beneficial effect on the treatment success.}, } @article {pmid29777834, year = {2018}, author = {Buttimer, C and Born, Y and Lucid, A and Loessner, MJ and Fieseler, L and Coffey, A}, title = {Erwinia amylovora phage vB_EamM_Y3 represents another lineage of hairy Myoviridae.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {505-514}, doi = {10.1016/j.resmic.2018.04.006}, pmid = {29777834}, issn = {1769-7123}, mesh = {DNA Replication ; DNA, Viral/*genetics ; Endopeptidases/biosynthesis/genetics ; Erwinia amylovora/ultrastructure/*virology ; *Genome, Viral ; Myoviridae/classification/*genetics/growth & development/ultrastructure ; Open Reading Frames ; Phylogeny ; Sequence Analysis, DNA ; Viral Proteins/genetics ; Virion/genetics/ultrastructure ; }, abstract = {To date, a small number of jumbo myoviruses have been reported to possess atypical whisker-like structures along the surface of their contractile tails. Erwinia amylovora phage vB_EamM_Y3 is another example. It possesses a genome of 261,365 kbp with 333 predicted ORFs. Using a combination of BLASTP, Interproscan and HHpred, about 21% of its putative proteins could be assigned functions involved in nucleotide metabolism, DNA replication, virion structure and cell wall degradation. The phage was found to have a signal-arrest-release (SAR) endolysin (Y3_301) possessing a soluble lytic transglycosylase domain. Like other SAR endolysins, inducible expression of Y3_301 caused Escherichia coli lysis, which is dependent on the presence of an N-terminal signal sequence. Phylogenetic analysis showed that its closest relatives are other jumbo phages including Pseudomonas aeruginosa phage PaBG and P. putida phage Lu11, sharing 105 and 87 homologous proteins respectively. Like these phages, Y3 also shares a distant relationship to Ralstonia solanacearum phage ΦRSL1 (sharing 55 homologous proteins). As these phages are unrelated to the Rak2-like group of hairy phages, Y3 along with Lu11 represent a second lineage of hairy myoviruses.}, } @article {pmid29777339, year = {2018}, author = {Zhou, P and Zhai, Z and Yao, X and Ma, P and Hao, Y}, title = {Characterization of a Cryptic Rolling-Circle Replication Plasmid pMK8 from Enterococcus durans 1-8.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1198-1205}, pmid = {29777339}, issn = {1432-0991}, support = {No. 21476250//National Natural Science Foundation of China/ ; }, mesh = {Amino Acid Sequence ; Animals ; Bacterial Proteins/chemistry/genetics ; Base Composition ; Base Sequence ; DNA Replication/*genetics ; DNA, Bacterial/genetics ; DNA, Circular/*genetics ; DNA, Single-Stranded/genetics ; Enterococcus/*genetics/isolation & purification ; Gene Dosage/genetics ; Milk/microbiology ; Open Reading Frames ; Plasmids/*genetics ; Protein Conformation ; Replication Origin/genetics ; Sequence Homology ; }, abstract = {A novel cryptic plasmid from Enterococcus durans 1-8, designated as pMK8, was sequenced and analyzed in this study. It consists of 3337 bp with a G + C content of 33.11%. Sequence analysis of pMK8 revealed three putative open reading frames (ORFs). Based on homology, two of them were identified as genes encoding replication initiation (RepC) and mobilization (Mob) protein, respectively. Sequence analysis revealed a pT181 family double-strand origin (dso) and a putative single-strand origin (sso) located upstream of the repC gene. Sequence homology analysis indicated that the sso belongs to the ssoW family. Southern hybridization confirmed the presence of single-strand DNA (ssDNA) intermediates, suggesting that pMK8 replicates via the RCR mechanism. Furthermore, the relative copy number of pMK8 was estimated by real-time PCR to be 175 ± 14 copies in each cell.}, } @article {pmid29777190, year = {2018}, author = {Lehoczky, JA and Tabin, CJ}, title = {Rethinking WNT signalling.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {495-496}, doi = {10.1038/d41586-018-04820-y}, pmid = {29777190}, issn = {1476-4687}, mesh = {*Wnt Signaling Pathway ; }, } @article {pmid29777189, year = {2018}, author = {Froeling, F and Tuveson, D}, title = {Pancreatic cancer foiled by a switch of tumour subtype.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {500-501}, doi = {10.1038/d41586-018-05129-6}, pmid = {29777189}, issn = {1476-4687}, mesh = {*Cell Line, Tumor ; Humans ; *Pancreatic Neoplasms ; }, } @article {pmid29777188, year = {2018}, author = {Walker, LC}, title = {Sabotage by the brain's supporting cells helps fuel neurodegeneration.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {499-500}, doi = {10.1038/d41586-018-04988-3}, pmid = {29777188}, issn = {1476-4687}, support = {P50 AG025688/AG/NIA NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; P51 RR000165/RR/NCRR NIH HHS/United States ; }, mesh = {*Brain ; *Neural Pathways ; }, } @article {pmid29777177, year = {2018}, author = {Flores, HA and O'Neill, SL}, title = {Controlling vector-borne diseases by releasing modified mosquitoes.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {8}, pages = {508-518}, doi = {10.1038/s41579-018-0025-0}, pmid = {29777177}, issn = {1740-1534}, abstract = {Aedes mosquito-transmitted diseases, such as dengue, Zika and chikungunya, are becoming major global health emergencies while old threats, such as yellow fever, are re-emerging. Traditional control methods, which have focused on reducing mosquito populations through the application of insecticides or preventing breeding through removal of larval habitat, are largely ineffective, as evidenced by the increasing global disease burden. Here, we review novel mosquito population reduction and population modification approaches with a focus on control methods based on the release of mosquitoes, including the release of Wolbachia-infected mosquitoes and strategies to genetically modify the vector, that are currently under development and have the potential to contribute to a reversal of the current alarming disease trends.}, } @article {pmid29777176, year = {2018}, author = {Hofer, U}, title = {Feasting on β-lactams.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {394-395}, doi = {10.1038/s41579-018-0030-3}, pmid = {29777176}, issn = {1740-1534}, } @article {pmid29777091, year = {2018}, author = {Eckles, D and Gordon, BR and Johnson, GA}, title = {Field studies of psychologically targeted ads face threats to internal validity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5254-E5255}, doi = {10.1073/pnas.1805363115}, pmid = {29777091}, issn = {1091-6490}, mesh = {*Advertising as Topic ; *Face ; Reproducibility of Results ; }, } @article {pmid29777090, year = {2018}, author = {Matz, SC and Kosinski, M and Nave, G and Stillwell, DJ}, title = {Reply to Eckles et al.: Facebook's optimization algorithms are highly unlikely to explain the effects of psychological targeting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5256-E5257}, pmid = {29777090}, issn = {1091-6490}, mesh = {*Algorithms ; *Social Media ; }, } @article {pmid29777089, year = {2018}, author = {Max, KEA and Bertram, K and Akat, KM and Bogardus, KA and Li, J and Morozov, P and Ben-Dov, IZ and Li, X and Weiss, ZR and Azizian, A and Sopeyin, A and Diacovo, TG and Adamidi, C and Williams, Z and Tuschl, T}, title = {Human plasma and serum extracellular small RNA reference profiles and their clinical utility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5334-E5343}, pmid = {29777089}, issn = {1091-6490}, support = {R01 HD086327/HD/NICHD NIH HHS/United States ; U19 CA179564/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adult ; Biomarkers/blood ; Cell-Free Nucleic Acids/*blood/genetics/isolation & purification ; Female ; Gene Library ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; MicroRNAs/blood/genetics ; }, abstract = {Circulating extracellular RNAs (exRNAs) have the potential to serve as biomarkers for a wide range of medical conditions. However, limitations in existing exRNA isolation methods and a lack of knowledge on parameters affecting exRNA variability in human samples may hinder their successful discovery and clinical implementation. Using combinations of denaturants, reducing agents, proteolysis, and revised organic extraction, we developed an automated, high-throughput approach for recovery of exRNAs and exDNA from the same biofluid sample. We applied this method to characterize exRNAs from 312 plasma and serum samples collected from 13 healthy volunteers at 12 time points over a 2-month period. Small RNA cDNA library sequencing identified nearly twofold increased epithelial-, muscle-, and neuroendocrine-cell-specific miRNAs in females, while fasting and hormonal cycle showed little effect. External standardization helped to detect quantitative differences in erythrocyte and platelet-specific miRNA contributions and in miRNA concentrations between biofluids. It also helped to identify a study participant with a unique exRNA phenotype featuring a miRNA signature of up to 20-fold elevated endocrine-cell-specific miRNAs and twofold elevated total miRNA concentrations stable for over 1 year. Collectively, these results demonstrate an efficient and quantitative method to discern exRNA phenotypes and suggest that plasma and serum RNA profiles are stable over months and can be routinely monitored in long-term clinical studies.}, } @article {pmid29776452, year = {2018}, author = {Chiwaridzo, M and Makotore, V and Dambi, JM and Munambah, N and Mhlanga, M}, title = {Work-related musculoskeletal disorders among registered general nurses: a case of a large central hospital in Harare, Zimbabwe.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {315}, pmid = {29776452}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Female ; Hospitals/statistics & numerical data ; Humans ; Low Back Pain/*epidemiology ; Male ; Middle Aged ; Musculoskeletal Diseases/*epidemiology ; Nurses/*statistics & numerical data ; Nursing Staff, Hospital/*statistics & numerical data ; Occupational Diseases/*epidemiology ; Prevalence ; Young Adult ; Zimbabwe/epidemiology ; }, abstract = {OBJECTIVE: Worldwide, work-related musculoskeletal disorders (WMSDs) are a common cause of morbidity affecting occupational individuals such as health-care professionals. However, nothing is known about WMSDs in hospital nurses in Zimbabwe. This study was conducted to provide cross-sectional evidence of the 12-month prevalence, consequences and factors associated with WMSDs among 208 nurses at Parirenyatwa Group of Hospitals (PGH).

RESULTS: The response rate for the study was 55.7%. The median age for the participants was 32.0 years (interquartile range = 29-36 years). The lifetime prevalence of WMSDs in nurses was 95.7% (n = 112). The first episodes were experienced in the first 5 years of working (n = 59, 52.7%). However, 82.1% (n = 96) nurses experienced WMSDs in the last 12 months. Low back pain was the most common WMSDs reported (n = 55, 67.9%). WMSDs were significantly associated with qualification attained, postgraduate ergonomic training and working experience. Overall, 87.5% (n = 84) nurses experienced at least one of the consequences of WMSDs. Cognisant of the limitations of the study, the present study found that WMSDs are a common occurrence among nurses at PGH. This creates a need for prompt hospital education programs aimed at raising awareness among nurses on the existence of WMSDs and the consequences at PGH.}, } @article {pmid29776449, year = {2018}, author = {Shams, S and Hashemi, A and Esmkhani, M and Kermani, S and Shams, E and Piccirillo, A}, title = {Imipenem resistance in clinical Escherichia coli from Qom, Iran.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {314}, pmid = {29776449}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*pharmacology ; Cross-Sectional Studies ; Disk Diffusion Antimicrobial Tests ; Drug Resistance, Bacterial/*genetics ; Escherichia coli/*drug effects/*genetics ; Genes, Bacterial/*genetics ; Hospitals/statistics & numerical data ; Humans ; Imipenem/*pharmacology ; Iran ; Microbial Sensitivity Tests ; Polymerase Chain Reaction ; beta-Lactam Resistance/genetics ; beta-Lactamases/*genetics ; }, abstract = {OBJECTIVE: The emergence of metallo-β-lactamase-producing Enterobacteriaceae is a worldwide health concern. In this study, the first evaluation of MBL genes, bla IMP and bla VIM , in Escherichia coli resistant to imipenem isolated from urine and blood specimens in Qom, Iran is described. Three hundred urine and blood specimens were analysed to detect the presence of E. coli. Resistance to imipenem and other antimicrobials was determined by disk diffusion and MIC. MBL production was screened using CDDT. PCR was also carried out to determine the presence of bla IMP and bla VIM genes in imipenem-resistant isolates.

RESULTS: In total, 160 E. coli isolates were collected from March to May 2016. According to disk diffusion, high-level of resistance (20%) to cefotaxime was observed, whereas the lowest (1%) was detected for tetracycline. In addition, five isolates showed resistance to imipenem with a MIC ≥ 4 µg/mL. CDDT test confirmed that five isolates were MBL-producing strains, but no bla IMP and bla VIM genes were detected. Results of this study show a very low level of resistance to imipenem in our geographical area.}, } @article {pmid29776448, year = {2018}, author = {Anato, M and Ketema, T}, title = {Anti-plasmodial activities of Combretum molle (Combretaceae) [Zwoo] seed extract in Swiss albino mice.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {312}, pmid = {29776448}, issn = {1756-0500}, mesh = {Animals ; Antiprotozoal Agents/administration & dosage/*pharmacology/toxicity ; *Combretum ; Disease Models, Animal ; Ethiopia ; Female ; Malaria/*drug therapy/parasitology ; Male ; Mice ; Plant Extracts/administration & dosage/*pharmacology/toxicity ; Plasmodium berghei/*drug effects ; *Seeds ; }, abstract = {OBJECTIVE: Objective of the study was to evaluate in vivo anti-plasmodial activities of Combretum molle seed extract.

METHODS: As a standard protocol, initially the acute toxicity of the plant seed extract was checked following single administration of crude seed extract of the plant at doses 500, 1000 and 2000 mg/kg. This was followed by evaluation of anti-plasmodial activity of crude seed extract of the plant following a 4 days suppressive test.

RESULTS: In acute toxicity study sign of toxicity was not observed. Also physical and behavioural changes were not detected. The crude seed extract of C. molle showed, 63.5% parasite suppression in mice infected with Plasmodium berghei ANKA (PbA) murine parasite and treated with 250 mg/kg of seed extract of C. molle. Relative survival time of mice treated with 250 mg/kg showed significantly longer survival than the negative control, while lower than mice treated with the standard drug, chloroquine. The plant seed extract on day-4 post-infection showed significant (P < 0.05) protection against body weight reduction, high body temperature and hemolysis of RBC at relatively lower doses. At optimum dose the crude extract of C. molle seed has good chemo-suppressive activity against PbA parasite and improved some clinical symptoms of malaria in mice.}, } @article {pmid29776447, year = {2018}, author = {Fiseha, T and Alemayehu, E and Kassahun, W and Adamu, A and Gebreweld, A}, title = {Factors associated with glycemic control among diabetic adult out-patients in Northeast Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {316}, pmid = {29776447}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Blood Glucose/*analysis/drug effects ; Cross-Sectional Studies ; *Diabetes Mellitus, Type 1/blood/drug therapy/epidemiology ; *Diabetes Mellitus, Type 2/blood/drug therapy/epidemiology ; Ethiopia ; Female ; Hospitals/*statistics & numerical data ; Humans ; Hypoglycemic Agents/*therapeutic use ; Male ; Middle Aged ; Outpatients/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to determine the status of glycemic control and identify factors associated with poor glycemic control among diabetic out-patients.

RESULTS: A hospital based cross-sectional study was conducted among randomly selected 384 (126 type 1 and 258 type 2) diabetic adults attending a hospital in Northeast Ethiopia from January 1 to April 30, 2017. Of the total participants, 70.8% had poor status of glycemic control (defined as mean fasting blood glucose level above 130 mg/dl). In the multivariate analysis, rural residence (AOR = 2.61, 95% CI 1.37-4.96), low educational level (AOR = 7.10, 95% CI 2.94-17.17) and longer duration of diabetes (AOR = 2.20, 95% CI 1.18-4.08) were significantly associated with increased odds of poor glycemic control. Moreover, merchants (AOR = 3.39, 95% CI 1.16-9.96) were significantly more likely to have poor glycemic control compared to government employee. Diabetic patients receiving oral anti-diabetics (AOR = 5.12, 95% CI 2.10-12.52) or insulin (AOR = 3.26, 95% CI 1.26-8.48) were more likely to be poorly controlled. These results highlight the needed for appropriate management of patients focusing on associated factors identified for poor glycemic control to maintain good glycemic control and improve adverse outcomes of the disease in this study setting.}, } @article {pmid29776445, year = {2018}, author = {Tianyi, FL and Agbor, VN and Tochie, JN and Kadia, BM and Nkwescheu, AS}, title = {Community-based audits of snake envenomations in a resource-challenged setting of Cameroon: case series.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {317}, pmid = {29776445}, issn = {1756-0500}, mesh = {Aged, 80 and over ; Antivenins/therapeutic use ; Cameroon ; Child, Preschool ; Community Health Services/*standards ; Fatal Outcome ; Female ; Humans ; Male ; Medical Audit/*standards ; Rural Health Services/*standards ; Snake Bites/*therapy ; }, abstract = {BACKGROUND: Snakebites are a major cause of mortality and morbidity worldwide with the highest mortality burden in poor rural areas of sub-Saharan Africa. Inadequate surveillance systems result in loss of morbidity and mortality data in these settings. Although rarely reported in these resource-constraint environments, community-based audits are recognised pivotal tools which could help update existing data and indicate key public health interventions to curb snakebite-related mortality. Herein, we present two cases of snakebite-related deaths in a rural Cameroonian community.

CASE PRESENTATIONS: The first case was a 3-year-old female who presented at a primary care health centre and was later referred due to absence of antivenom serum (AVS). However, she had an early fatal outcome before getting to the referral hospital. The second case was an 80-year-old traditional healer who got bitten while attempting to kill a snake. He died before hospital presentation.

CONCLUSION: Community-based audits help identify key intervention points to curb snakebite mortality in high-risk rural areas like ours. From our audits, we note a remarkable absence of affordable AVS in rural health facilities in Cameroon. We recommend frequent community health education sessions on preventing snakebites; continuous training modules for health personnel from high-risk areas; training traditional healers on the importance of AVS in managing cases of snakebite envenoming, and the need for timely hospital presentation; and setting up context-specific approaches to rapidly transport snakebite victims to hospitals.}, } @article {pmid29776441, year = {2018}, author = {Girmay, A and Marye, T and Haftu, M and G/Her, D and Brhanu, T and Gerensea, H}, title = {Patients expectation strongly associated with patients perception to nursing care: hospital based cross sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {310}, pmid = {29776441}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Ethiopia ; Female ; *Health Knowledge, Attitudes, Practice ; Hospitals/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Nursing Care/*statistics & numerical data ; Patient Acceptance of Health Care/*statistics & numerical data ; Patient Preference/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: Nursing care is one of the most important components of health care and patient expectation toward nursing care is being rising. Accordingly, patients' expectation needs to be managed adequately in order to improve outcomes and decrease liability through their perception. To improve the outcome based on the expectation of patients, we need to consider patients' perception to the care they received. So this study aims to identifies the perceptions toward nursing care and their associated factors.

RESULT: From a total of 281 admitted patients 151 (53.7%) were females; 136 (48.4%) were found in the age group of 21-30 years with mean age of 30 (11 ± SD) years. The mean score of overall perception were 62.6 ± 17.9 (95% CI 60.79-64.37). Among all 154 (54.8%) participants had poor perception to nursing care. Occupation, ward and expectation had association with perception. Patient's level of perception towards nursing care was poor (54.7%) and ward where patients admitted, expectation of patients, occupation of patients and duration of hospital stay were significantly associated with patients' perception. So that health institutions and nurses should focus on perception of their clients.}, } @article {pmid29776438, year = {2018}, author = {Suzuki, K and Onishi, T and Nakada, C and Takei, S and Daniels, MJ and Nakano, M and Matsuda, T and Nagai, T}, title = {Uninterrupted monitoring of drug effects in human-induced pluripotent stem cell-derived cardiomyocytes with bioluminescence Ca2+ microscopy.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {313}, pmid = {29776438}, issn = {1756-0500}, support = {JP26251018//Japan Society for the Promotion of Science/ ; }, mesh = {*Calcium ; *Calcium Signaling ; Drug Evaluation, Preclinical/*methods ; High-Throughput Screening Assays/*methods ; Humans ; *Induced Pluripotent Stem Cells ; Luminescent Measurements/*methods ; Microscopy/*methods ; Myocytes, Cardiac/*drug effects ; }, abstract = {OBJECTIVE: Cardiomyocytes derived from human-induced pluripotent stem cells are a powerful platform for high-throughput drug screening in vitro. However, current modalities for drug testing, such as electrophysiology and fluorescence imaging have inherent drawbacks. To circumvent these problems, we report the development of a bioluminescent Ca2+ indicator GmNL(Ca2+), and its application in a customized microscope for high-throughput drug screening.

RESULTS: GmNL(Ca2+) gives a 140% signal change with Ca2+, and can image drug-induced changes of Ca2+ dynamics in cultured cells. Since bioluminescence requires application of a chemical substrate, which is consumed over ~ 30 min we made a dedicated microscope with automated drug dispensing inside a light-tight box, to control drug addition. To overcome thermal instability of the luminescent substrate, or small molecule, dual climate control enables distinct temperature settings in the drug reservoir and the biological sample. By combining GmNL(Ca2+) with this adaptation, we could image spontaneous Ca2+ transients in cultured cardiomyocytes and phenotype their response to well-known drugs without accessing the sample directly. In addition, the bioluminescent strategy demonstrates minimal perturbation of contractile parameters and long-term observation attributable to lack of phototoxicity and photobleaching. Overall, bioluminescence may enable more accurate drug screening in a high-throughput manner.}, } @article {pmid29776435, year = {2018}, author = {Romano, KA and Dill-McFarland, KA and Kasahara, K and Kerby, RL and Vivas, EI and Amador-Noguez, D and Herd, P and Rey, FE}, title = {Fecal Aliquot Straw Technique (FAST) allows for easy and reproducible subsampling: assessing interpersonal variation in trimethylamine-N-oxide (TMAO) accumulation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {91}, pmid = {29776435}, issn = {2049-2618}, support = {AG041868/NH/NIH HHS/United States ; 2016-67017-24416//National Institute of Food and Agriculture/International ; R01 AG041868/AG/NIA NIH HHS/United States ; NLM5T15LM007359//U.S. National Library of Medicine/International ; T15 LM007359/LM/NLM NIH HHS/United States ; P30 AG017266/AG/NIA NIH HHS/United States ; R01 DK108259/DK/NIDDK NIH HHS/United States ; AG017266//Center for the Demography of Health and Aging/International ; DK108259-01/NH/NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification/*genetics/isolation & purification ; Base Sequence ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Methylamines/*metabolism ; Mice ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Specimen Handling/*methods ; }, abstract = {BACKGROUND: Convenient, reproducible, and rapid preservation of unique biological specimens is pivotal to their use in microbiome analyses. As an increasing number of human studies incorporate the gut microbiome in their design, there is a high demand for streamlined sample collection and storage methods that are amenable to different settings and experimental needs. While several commercial kits address collection/shipping needs for sequence-based studies, these methods do not preserve samples properly for studies that require viable microbes.

RESULTS: We describe the Fecal Aliquot Straw Technique (FAST) of fecal sample processing for storage and subsampling. This method uses a straw to collect fecal material from samples recently voided or preserved at low temperature but not frozen (i.e., 4 °C). Different straw aliquots collected from the same sample yielded highly reproducible communities as disclosed by 16S rRNA gene sequencing; operational taxonomic units that were lost, or gained, between the two aliquots represented very low-abundance taxa (i.e., < 0.3% of the community). FAST-processed samples inoculated into germ-free animals resulted in gut communities that retained on average ~ 80% of the donor's bacterial community. Assessment of choline metabolism and trimethylamine-N-oxide accumulation in transplanted mice suggests large interpersonal variation.

CONCLUSIONS: Overall, FAST allows for repetitive subsampling without thawing of the specimens and requires minimal supplies and storage space, making it convenient to utilize both in the lab and in the field. FAST has the potential to advance microbiome research through easy, reproducible sample processing.}, } @article {pmid29776433, year = {2018}, author = {Del Valle-Mendoza, J and Silva-Caso, W and Aguilar-Luis, MA and Del Valle-Vargas, C and Cieza-Mora, E and Martins-Luna, J and Aquino-Ortega, R and Silva-Vásquez, A and Bazán-Mayra, J and Weilg, P}, title = {Bordetella pertussis in children hospitalized with a respiratory infection: clinical characteristics and pathogen detection in household contacts.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {318}, pmid = {29776433}, issn = {1756-0500}, support = {401//Universidad Peruana de Ciencias Aplicadas (UPC)/ ; }, mesh = {Bordetella pertussis/*isolation & purification/pathogenicity ; Child, Preschool ; Female ; Hospitals/*statistics & numerical data ; Humans ; Infant ; Male ; Peru/epidemiology ; Polymerase Chain Reaction ; *Whooping Cough/diagnosis/epidemiology/microbiology ; }, abstract = {OBJECTIVE: Describe the prevalence of Bordetella pertussis via PCR in children under 5 years old hospitalized as probable cases of pertussis and report the most common clinical features among them.

RESULTS: A positive PCR result for B. pertussis was observed in 20.5% of our samples (18/88), one-third of them were from infants between 2 and 3 months old. The most common symptoms were paroxysms of coughing (88.9%), difficulty breathing (72.2%), cyanosis (77.8%) and fever (50%). The mother was the most common symptomatic carrier (27.8%), followed by uncles/aunts (22.2%) among children with pertussis.}, } @article {pmid29776430, year = {2018}, author = {Grandjean-Lapierre, S and Thiberville, SD and Fellag, M and Eghazarian, C and Bouzid, F and Gavril, C and Drancourt, M}, title = {Recurrent bilateral Mycobacterium bovis necrotizing epididymitis: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {308}, pmid = {29776430}, issn = {1756-0500}, mesh = {Animals ; Camelus ; Epididymitis/*diagnosis/etiology/*microbiology/pathology ; Humans ; Male ; Middle Aged ; Milk ; Mycobacterium bovis/*pathogenicity ; Necrosis/pathology ; Recurrence ; Zoonoses ; }, abstract = {BACKGROUND: Mycobacterium bovis causing tuberculosis in animals is responsible for zoonotic tuberculosis in patients. Veterinary control measures and milk pasteurization has led to a significant decrease in human cases of M. bovis infections in developed countries.

CASE PRESENTATION: We diagnosed recurrent M. bovis epididymitis in a 63-year old Caucasian man without any signs of pulmonary or disseminated disease. Relevant epidemiological expositions included camel milk drinking during prolonged travels in Niger, prior to initial clinical manifestations. The diagnosis was firmly established by mass spectrometry and DNA sequencing on epididymis surgical biopsy specimens. We detail therapeutic management which included surgical epididymectomy and hydrocele repair.

CONCLUSION: As for other M. tuberculosis complex species, the genitourinary tract represents a frequent site of secondary dissemination and latency for M. bovis. Isolated epididymis infection is a newly documented manifestation of M. bovis disease.}, } @article {pmid29776426, year = {2018}, author = {Weilg, C and Troyes, L and Villegas, Z and Silva-Caso, W and Mazulis, F and Febres, A and Troyes, M and Aguilar-Luis, MA and Del Valle-Mendoza, J}, title = {Detection of Zika virus infection among asymptomatic pregnant women in the North of Peru.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {311}, pmid = {29776426}, issn = {1756-0500}, support = {164-2016-FONDECYT//Cienciactiva of CONCYTEC/ ; 116-PNICP-PIAP-2015//Programa Nacional de Innovación para la Competitividad y Productividad (Innóvate Perú)/ ; }, mesh = {Adolescent ; Adult ; *Disease Outbreaks/statistics & numerical data ; Female ; Humans ; Peru/epidemiology ; Pregnancy ; Pregnancy Complications, Infectious/*diagnosis/epidemiology ; Young Adult ; Zika Virus Infection/*diagnosis/epidemiology ; }, abstract = {OBJECTIVE: To report an outbreak of ZIKV infection among asymptomatic pregnant women during 2016 in the city of Jaen, Cajamarca.

RESULTS: Zika virus RNA was detected in 3.2% (n = 36) of cases by RT-PCR. The mean age of patients positive for ZIKV infection was 29.6 years. 7 patients (19.4%) infected with ZIKV were in their first-trimester of gestation, 13 (36.1%) were in their second-trimester, and 16 (44%) were in their third-trimester. All of the infected pregnant women were asymptomatic. ZIKV infection remains a major public health issue that calls for constant epidemiological surveillance. It can cause the congenital Zika virus syndrome in the newborns of infected mothers. The lack of molecular diagnostic methods in isolated localities and the similarity of symptoms to other arboviral infections, lead to an under-diagnosis of this disease in endemic areas.}, } @article {pmid29776407, year = {2018}, author = {Lindsey, ARI and Kelkar, YD and Wu, X and Sun, D and Martinson, EO and Yan, Z and Rugman-Jones, PF and Hughes, DST and Murali, SC and Qu, J and Dugan, S and Lee, SL and Chao, H and Dinh, H and Han, Y and Doddapaneni, HV and Worley, KC and Muzny, DM and Ye, G and Gibbs, RA and Richards, S and Yi, SV and Stouthamer, R and Werren, JH}, title = {Comparative genomics of the miniature wasp and pest control agent Trichogramma pretiosum.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {54}, pmid = {29776407}, issn = {1741-7007}, support = {U54 HG003273/HG/NHGRI NIH HHS/United States ; }, abstract = {BACKGROUND: Trichogrammatids are minute parasitoid wasps that develop within other insect eggs. They are less than half a millimeter long, smaller than some protozoans. The Trichogrammatidae are one of the earliest branching families of Chalcidoidea: a diverse superfamily of approximately half a million species of parasitoid wasps, proposed to have evolved from a miniaturized ancestor. Trichogramma are frequently used in agriculture, released as biological control agents against major moth and butterfly pests. Additionally, Trichogramma are well known for their symbiotic bacteria that induce asexual reproduction in infected females. Knowledge of the genome sequence of Trichogramma is a major step towards further understanding its biology and potential applications in pest control.

RESULTS: We report the 195-Mb genome sequence of Trichogramma pretiosum and uncover signatures of miniaturization and adaptation in Trichogramma and related parasitoids. Comparative analyses reveal relatively rapid evolution of proteins involved in ribosome biogenesis and function, transcriptional regulation, and ploidy regulation. Chalcids also show loss or especially rapid evolution of 285 gene clusters conserved in other Hymenoptera, including many that are involved in signal transduction and embryonic development. Comparisons between sexual and asexual lineages of Trichogramma pretiosum reveal that there is no strong evidence for genome degradation (e.g., gene loss) in the asexual lineage, although it does contain a lower repeat content than the sexual lineage. Trichogramma shows particularly rapid genome evolution compared to other hymenopterans. We speculate these changes reflect adaptations to miniaturization, and to life as a specialized egg parasitoid.

CONCLUSIONS: The genomes of Trichogramma and related parasitoids are a valuable resource for future studies of these diverse and economically important insects, including explorations of parasitoid biology, symbiosis, asexuality, biological control, and the evolution of miniaturization. Understanding the molecular determinants of parasitism can also inform mass rearing of Trichogramma and other parasitoids for biological control.}, } @article {pmid29776387, year = {2018}, author = {Cirilli, M and Giovannini, D and Ciacciulli, A and Chiozzotto, R and Gattolin, S and Rossini, L and Liverani, A and Bassi, D}, title = {Integrative genomics approaches validate PpYUC11-like as candidate gene for the stony hard trait in peach (P. persica L. Batsch).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {88}, pmid = {29776387}, issn = {1471-2229}, mesh = {Fruit/anatomy & histology/*genetics ; Gene Expression Profiling ; Genes, Plant/*genetics/physiology ; Genetic Loci/genetics ; Genetic Markers ; Genome, Plant/genetics ; Genome-Wide Association Study ; Genomics ; Linkage Disequilibrium ; Prunus persica/anatomy & histology/*genetics ; Quantitative Trait, Heritable ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Texture is one of the most important fruit quality attributes. In peach, stony hard (SH) is a recessive monogenic trait (hd/hd) that confers exceptionally prolonged firm flesh to fully ripe fruit. Previous studies have shown that the SH mutation affects the fruit ability to synthesize appropriate amounts of indol-3-acetic acid (IAA), which orchestrates the ripening processes through the activation of system 2 ethylene pathway. Allelic variation in a TC microsatellite located within the first intron of PpYUC11-like (a YUCCA-like auxin-biosynthesis gene) has been recently proposed as the causal mutation of the SH phenotype.

RESULTS: The simple genetic determinism of the SH trait has been clarified through genome-wide association and LD analyses in a diverse set of accessions, restricting the hd locus to an interval of about 1.8 Mbp in chromosome 6. The comparison of fruit transcriptome data from non-SH (melting flesh) and SH accessions provided an expression patterns overview of the annotated transcripts within the hd locus, confirming the absence of PpYUC11-like expression in SH fruits. To explore further possible associations between genomic variants at the hd locus and the SH phenotype, re-sequencing data of the SH accession 'D41-62' were compared with several SH and non-SH accessions with different genetic backgrounds. A further step of validation was provided through the evaluation of variant-trait association in two bi-parental F2 populations issued from the SH accession 'D41-62' and a panel of advanced breeding selections, showing perfect co-segregation of the PpYUC11-like intron TC20 allele and the SH phenotype.

CONCLUSIONS: In this study, we provide a multi-level validation of the genetic control of the SH trait through the integration of genome-wide association mapping, transcriptome analysis and whole-genome resequencing data for SH and non-SH accessions, and marker-trait association in a panel of advanced breeding selections and segregating progenies. Collectively, our data confirm with high confidence the role of allelic variation at PpYUC11-like locus as the genetic determinant of the SH trait, opening interesting perspectives at both biological and applied research level.}, } @article {pmid29776372, year = {2018}, author = {Lovell, PV and Huizinga, NA and Getachew, A and Mees, B and Friedrich, SR and Wirthlin, M and Mello, CV}, title = {Curation of microarray oligonucleotides and corresponding ESTs/cDNAs used for gene expression analysis in zebra finches.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {309}, pmid = {29776372}, issn = {1756-0500}, support = {DC014432//National Institute on Deafness and Other Communication Disorders/ ; GM120464//National Institute of General Medical Sciences/ ; 143602//Directorate for Biological Sciences/ ; }, mesh = {Animals ; *Expressed Sequence Tags ; Finches/*genetics ; *Gene Expression ; Gene Expression Profiling/*methods ; Oligonucleotide Array Sequence Analysis/*methods ; *Vocalization, Animal ; }, abstract = {OBJECTIVES: Zebra finches are a major model organism for investigating mechanisms of vocal learning, a trait that enables spoken language in humans. The development of cDNA collections with expressed sequence tags (ESTs) and microarrays has allowed for extensive molecular characterizations of circuitry underlying vocal learning and production. However, poor database curation can lead to errors in transcriptome and bioinformatics analyses, limiting the impact of these resources. Here we used genomic alignments and synteny analysis for orthology verification to curate and reannotate ~ 35% of the oligonucleotides and corresponding ESTs/cDNAs that make-up Agilent microarrays for gene expression analysis in finches.

DATA DESCRIPTION: We found that: (1) 5475 out of 43,084 oligos (a) failed to align to the zebra finch genome, (b) aligned to multiple loci, or (c) aligned to Chr_un only, and thus need to be flagged until a better genome assembly is available, or (d) reflect cloning artifacts; (2) Out of 9635 valid oligos examined further, 3120 were incorrectly named, including 1533 with no known orthologs; and (3) 2635 oligos required name update. The resulting curated dataset provides a reference for correcting gene identification errors in previous finch microarrays studies, and avoiding such errors in future studies.}, } @article {pmid29776341, year = {2018}, author = {Warsi, OM and Andersson, DI and Dykhuizen, DE}, title = {Different adaptive strategies in E. coli populations evolving under macronutrient limitation and metal ion limitation.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {72}, pmid = {29776341}, issn = {1471-2148}, mesh = {*Adaptation, Physiological/drug effects ; Alleles ; Bacterial Toxins/genetics ; Base Sequence ; Biological Evolution ; DNA Transposable Elements/genetics ; Escherichia coli/drug effects/genetics/*physiology ; Escherichia coli Proteins/genetics ; Genes, Bacterial ; Genetic Fitness ; Genome, Bacterial ; Hydrophobic and Hydrophilic Interactions ; Ions ; Lipopolysaccharides/pharmacology ; Loss of Function Mutation/genetics ; Magnesium/*pharmacology ; Metals/*pharmacology ; Nitrogen/*pharmacology ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Adaptive responses to nutrient limitation involve mutations that increase the efficiency of usage or uptake of the limiting nutrient. However, starvation of different nutrients has contrasting effects on physiology, resulting in different evolutionary responses. Most studies performed to understand these evolutionary responses have focused only on macronutrient limitation. Hence our understanding of adaptation under limitation of other forms of nutrients is limited. In this study, we compared the evolutionary response in populations evolving under growth-limiting conditions for a macronutrient and a major cation.

RESULTS: We evolved eight populations of E. coli in nutrient-limited chemostats for 400 generations to identify the genetic basis of the mechanisms involved in efficient usage of two nutrients: nitrogen and magnesium. Our population genomic sequencing work, based on this study and previous work, allowed us to identify targets of selection under these nutrient limiting conditions. Global transcriptional regulators glnGL were targets of selection under nitrogen starvation, while proteins involved in outer-membrane biogenesis (genes from the lpt operon) were targets of selection under magnesium starvation. The protein involved in cell-cycle arrest (yhaV) was a target of selection in both environments. We re-constructed specific mutants to analyze the effect of individual mutations on fitness in nutrient limiting conditions in chemostats and in batch cultures. We further demonstrated that adaptation to nitrogen starvation proceeds via a nutrient specific mechanism, while that to magnesium starvation involves a more general mechanism.

CONCLUSIONS: Our results show two different forms of adaptive strategies under limitation of nutrients that effect cellular physiology in different ways. Adaptation to nitrogen starvation proceeds by upregulation of transcriptional regulator glnG and subsequently of transporter protein amtB, both of which results in increased nitrogen scavenging ability of the cell. On the other hand, adaptation to magnesium starvation proceeds via the restructuring of the cell outer-membrane, allowing magnesium to be redistributed to other biological processes. Also, adaptation to the chemostat environment involves selection for loss of function mutations in genes that under nutrient-limiting conditions interfere with continuous growth.}, } @article {pmid29776340, year = {2018}, author = {Armstrong, AF and Grosberg, RK}, title = {The developmental transcriptomes of two sea biscuit species with differing larval types.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {368}, pmid = {29776340}, issn = {1471-2164}, support = {DGE-1650042//Directorate for Biological Sciences/ ; OCE-1459815//National Science Foundation/ ; ACI-1548562//National Science Foundation/ ; }, mesh = {Animals ; *Gene Expression Profiling ; Larva/*genetics/*growth & development ; Sea Urchins/*genetics/*growth & development ; }, abstract = {BACKGROUND: Larval developmental patterns are extremely varied both between and within phyla, however the genetic mechanisms leading to this diversification are poorly understood. We assembled and compared the developmental transcriptomes for two sea biscuit species (Echinodermata: Echinoidea) with differing patterns of larval development, to provide a resource for investigating the evolution of alternate life cycles. One species (Clypeaster subdepressus) develops via an obligately feeding larva which metamorphoses 3-4 weeks after fertilization; the other (Clypeaster rosaceus) develops via a rare, intermediate larval type-facultative feeding- and can develop through metamorphosis entirely based on egg provisioning in under one week.

RESULTS: Overall, the two transcriptomes are highly similar, containing largely orthologous contigs with similar functional annotation. However, we found distinct differences in gene expression patterns between the two species. Larvae from C. rosaceus, the facultative planktotroph, turned genes on at earlier stages and had less differentiation in gene expression between larval stages, whereas, C. subdepressus showed a higher degree of stage-specific gene expression.

CONCLUSION: This study is the first genetic analysis of a species with facultatively feeding larvae. Our results are consistent with known developmental differences between the larval types and raise the question of whether earlier onset of developmental genes is a key step in the evolution of a reduced larval period. By publishing a transcriptome for this rare, intermediate, larval type, this study adds developmental breadth to the current genetic resources, which will provide a valuable tool for future research on echinoderm development as well as studies on the evolution of development in general.}, } @article {pmid29776339, year = {2018}, author = {Campos, B and Fletcher, D and Piña, B and Tauler, R and Barata, C}, title = {Differential gene transcription across the life cycle in Daphnia magna using a new all genome custom-made microarray.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {370}, pmid = {29776339}, issn = {1471-2164}, support = {ERC-2012-AdG-320737//European Research Council/International ; CTM2014-51985-R//Ministerio de Economía y Competitividad/ ; }, mesh = {Animals ; Daphnia/*genetics/*growth & development ; Genomics/*methods ; Life Cycle Stages/*genetics ; Oligonucleotide Array Sequence Analysis/*methods ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Unravelling the link between genes and environment across the life cycle is a challenging goal that requires model organisms with well-characterized life-cycles, ecological interactions in nature, tractability in the laboratory, and available genomic tools. Very few well-studied invertebrate model species meet these requirements, being the waterflea Daphnia magna one of them. Here we report a full genome transcription profiling of D. magna during its life-cycle. The study was performed using a new microarray platform designed from the complete set of gene models representing the whole transcribed genome of D. magna.

RESULTS: Up to 93% of the existing 41,317 D. magna gene models showed differential transcription patterns across the developmental stages of D. magna, 59% of which were functionally annotated. Embryos showed the highest number of unique transcribed genes, mainly related to DNA, RNA, and ribosome biogenesis, likely related to cellular proliferation and morphogenesis of the several body organs. Adult females showed an enrichment of transcripts for genes involved in reproductive processes. These female-specific transcripts were essentially absent in males, whose transcriptome was enriched in specific genes of male sexual differentiation genes, like doublesex.

CONCLUSION: Our results define major characteristics of transcriptional programs involved in the life-cycle, differentiate males and females, and show that large scale gene-transcription data collected in whole animals can be used to identify genes involved in specific biological and biochemical processes.}, } @article {pmid29776336, year = {2018}, author = {Sann, M and Niehuis, O and Peters, RS and Mayer, C and Kozlov, A and Podsiadlowski, L and Bank, S and Meusemann, K and Misof, B and Bleidorn, C and Ohl, M}, title = {Phylogenomic analysis of Apoidea sheds new light on the sister group of bees.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {71}, pmid = {29776336}, issn = {1471-2148}, support = {OH81/9-1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Animals ; Bees/*classification/*genetics ; *Genomics ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; Social Behavior ; Transcriptome/genetics ; Wasps/genetics ; }, abstract = {BACKGROUND: Apoid wasps and bees (Apoidea) are an ecologically and morphologically diverse group of Hymenoptera, with some species of bees having evolved eusocial societies. Major problems for our understanding of the evolutionary history of Apoidea have been the difficulty to trace the phylogenetic origin and to reliably estimate the geological age of bees. To address these issues, we compiled a comprehensive phylogenomic dataset by simultaneously analyzing target DNA enrichment and transcriptomic sequence data, comprising 195 single-copy protein-coding genes and covering all major lineages of apoid wasps and bee families.

RESULTS: Our compiled data matrix comprised 284,607 nucleotide sites that we phylogenetically analyzed by applying a combination of domain- and codon-based partitioning schemes. The inferred results confirm the polyphyletic status of the former family "Crabronidae", which comprises nine major monophyletic lineages. We found the former subfamily Pemphredoninae to be polyphyletic, comprising three distantly related clades. One of them, Ammoplanina, constituted the sister group of bees in all our analyses. We estimate the origin of bees to be in the Early Cretaceous (ca. 128 million years ago), a time period during which angiosperms rapidly radiated. Finally, our phylogenetic analyses revealed that within the Apoidea, (eu)social societies evolved exclusively in a single clade that comprises pemphredonine and philanthine wasps as well as bees.

CONCLUSION: By combining transcriptomic sequences with those obtained via target DNA enrichment, we were able to include an unprecedented large number of apoid wasps in a phylogenetic study for tracing the phylogenetic origin of bees. Our results confirm the polyphyletic nature of the former wasp family Crabonidae, which we here suggest splitting into eight families. Of these, the family Ammoplanidae possibly represents the extant sister lineage of bees. Species of Ammoplanidae are known to hunt thrips, of which some aggregate on flowers and feed on pollen. The specific biology of Ammoplanidae as predators indicates how the transition from a predatory to pollen-collecting life style could have taken place in the evolution of bees. This insight plus the finding that (eu)social societies evolved exclusively in a single subordinated lineage of apoid wasps provides new perspectives for future comparative studies.}, } @article {pmid29776334, year = {2018}, author = {Jordán-Pla, A and Yu, S and Waldholm, J and Källman, T and Östlund Farrants, AK and Visa, N}, title = {SWI/SNF regulates half of its targets without the need of ATP-driven nucleosome remodeling by Brahma.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {367}, pmid = {29776334}, issn = {1471-2164}, mesh = {Adenosine Triphosphatases/metabolism ; Adenosine Triphosphate/*metabolism ; Animals ; Cell Cycle Proteins/*metabolism ; Cell Line ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/*genetics/*metabolism ; Genomics ; Nucleosomes/*metabolism ; Promoter Regions, Genetic/genetics ; Ribonucleoprotein, U1 Small Nuclear/*metabolism ; Trans-Activators/*metabolism ; }, abstract = {BACKGROUND: Brahma (BRM) is the only catalytic subunit of the SWI/SNF chromatin-remodeling complex of Drosophila melanogaster. The function of SWI/SNF in transcription has long been attributed to its ability to remodel nucleosomes, which requires the ATPase activity of BRM. However, recent studies have provided evidence for a non-catalytic function of BRM in the transcriptional regulation of a few specific genes.

RESULTS: Here we have used RNA-seq and ChIP-seq to identify the BRM target genes in S2 cells, and we have used a catalytically inactive BRM mutant (K804R) that is unable to hydrolyze ATP to investigate the magnitude of the non-catalytic function of BRM in transcription regulation. We show that 49% of the BRM target genes in S2 cells are regulated through mechanisms that do not require BRM to have an ATPase activity. We also show that the catalytic and non-catalytic mechanisms of SWI/SNF regulation operate on two subsets of genes that differ in promoter architecture and are linked to different biological processes.

CONCLUSIONS: This study shows that the non-catalytic role of SWI/SNF in transcription regulation is far more prevalent than previously anticipated and that the genes that are regulated by SWI/SNF through ATPase-dependent and ATPase-independent mechanisms have specialized roles in different cellular and developmental processes.}, } @article {pmid29776333, year = {2018}, author = {Dong, H and Shi, S and Zhang, C and Zhu, S and Li, M and Tan, J and Yu, Y and Lin, L and Jia, S and Wang, X and Wu, Y and Liu, Y}, title = {Transcriptomic analysis of genes in soybean in response to Peronospora manshurica infection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {366}, pmid = {29776333}, issn = {1471-2164}, support = {2016ZX08009003-005-006//The development of new varieties of animals and crops/ ; }, mesh = {Disease Resistance/genetics ; *Gene Expression Profiling ; Genes, Plant/*genetics ; Peronospora/*physiology ; Plant Diseases/*microbiology ; Soybeans/*genetics/immunology/*microbiology ; }, abstract = {BACKGROUND: Soybean downy mildew (SDM), caused by Peronospora manshurica (Pm), is a major fungal disease in soybean. To date, little is known regarding the defense mechanism at molecular level and how soybean plants response to Pm infection. In this study, differential gene expression in SDM-resistant (HR) and SDM-susceptible (HS) genotype was analyzed by RNA-seq to identify differentially expressed genes (DEGs) following Pm infection.

RESULTS: Of a total of 55,017 genes mapped to the soybean reference genome sequences, 2581 DEGs were identified. Clustering analysis of DEGs revealed that these genes could be grouped into 8 clusters with distinct expression patterns. Functional annotation based on gene ontology (GO) and KEGG analysis indicated they involved in diverse metabolism pathways. Of particular interest were the detected DEGs participating in SA/ROS and JA signalling transduction and plant/pathogen interaction.

CONCLUSION: Totally, 52 DEGs with P value < 0.001 and log2 fold change > 2 or < - 2 upon fungal inoculation were identified, suggesting they were SDM defense responsive genes. These findings have paved way in further functional characterization of candidate genes and subsequently can be used in breeding of elite soybean varieties with better SDM-resistance.}, } @article {pmid29776332, year = {2018}, author = {Braun, DM and Chung, I and Kepper, N and Deeg, KI and Rippe, K}, title = {TelNet - a database for human and yeast genes involved in telomere maintenance.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {32}, pmid = {29776332}, issn = {1471-2156}, support = {CancerTelSys (01ZX1302)//Bundesministerium für Forschung und Technologie/ ; }, abstract = {BACKGROUND: The ends of linear chromosomes, the telomeres, comprise repetitive DNA sequences in complex with proteins that protects them from being processed by the DNA repair machinery. Cancer cells need to counteract the shortening of telomere repeats during replication for their unlimited proliferation by reactivating the reverse transcriptase telomerase or by using the alternative lengthening of telomeres (ALT) pathway. The different telomere maintenance (TM) mechanisms appear to involve hundreds of proteins but their telomere repeat length related activities are only partly understood. Currently, a database that integrates information on TM relevant genes is missing.

DESCRIPTION: To provide a resource for studies that dissect TM features, we here introduce the TelNet database at http://www.cancertelsys.org/telnet/ . It offers a comprehensive compilation of more than 2000 human and 1100 yeast genes linked to telomere maintenance. These genes were annotated in terms of TM mechanism, associated specific functions and orthologous genes, a TM significance score and information from peer-reviewed literature. This TM information can be retrieved via different search and view modes and evaluated for a set of genes as demonstrated for an exemplary application.

CONCLUSION: TelNet supports the annotation of genes identified from bioinformatics analysis pipelines to reveal possible connections with TM networks. We anticipate that TelNet will be a helpful resource for researchers that study telomeres.}, } @article {pmid29776331, year = {2018}, author = {Chen, M and Wang, J and Wang, Y and Wu, Y and Fu, J and Liu, JF}, title = {Genome-wide detection of selection signatures in Chinese indigenous Laiwu pigs revealed candidate genes regulating fat deposition in muscle.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {31}, pmid = {29776331}, issn = {1471-2156}, support = {2013AA102503//the 863 State High-tech Development Plan/ ; 31372293//National Natural Science Foundations of China/ ; SDAIT-08-03//Shandong Swine Industry Technology System Innovation/ ; (CXGC2016A04)//Agricultural Science and Technology Innovation Project of SAAS/ ; (ZR2017MC043)//the Natural Science Foundations of Shandong Province of China/ ; }, abstract = {BACKGROUND: Currently, genome-wide scans for positive selection signatures in commercial breed have been investigated. However, few studies have focused on selection footprints of indigenous breeds. Laiwu pig is an invaluable Chinese indigenous pig breed with extremely high proportion of intramuscular fat (IMF), and an excellent model to detect footprint as the result of natural and artificial selection for fat deposition in muscle.

RESULT: In this study, based on GeneSeek Genomic profiler Porcine HD data, three complementary methods, FST, iHS (integrated haplotype homozygosity score) and CLR (composite likelihood ratio), were implemented to detect selection signatures in the whole genome of Laiwu pigs. Totally, 175 candidate selected regions were obtained by at least two of the three methods, which covered 43.75 Mb genomic regions and corresponded to 1.79% of the genome sequence. Gene annotation of the selected regions revealed a list of functionally important genes for feed intake and fat deposition, reproduction, and immune response. Especially, in accordance to the phenotypic features of Laiwu pigs, among the candidate genes, we identified several genes, NPY1R, NPY5R, PIK3R1 and JAKMIP1, involved in the actions of two sets of neurons, which are central regulators in maintaining the balance between food intake and energy expenditure.

CONCLUSIONS: Our results identified a number of regions showing signatures of selection, as well as a list of functionally candidate genes with potential effect on phenotypic traits, especially fat deposition in muscle. Our findings provide insights into the mechanisms of artificial selection of fat deposition and further facilitate follow-up functional studies.}, } @article {pmid29776330, year = {2018}, author = {Li, X and Fu, Y and Wang, X and Qiu, W}, title = {Robust joint score tests in the application of DNA methylation data analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {174}, pmid = {29776330}, issn = {1471-2105}, abstract = {BACKGROUND: Recently differential variability has been showed to be valuable in evaluating the association of DNA methylation to the risks of complex human diseases. The statistical tests based on both differential methylation level and differential variability can be more powerful than those based only on differential methylation level. Anh and Wang (2013) proposed a joint score test (AW) to simultaneously detect for differential methylation and differential variability. However, AW's method seems to be quite conservative and has not been fully compared with existing joint tests.

RESULTS: We proposed three improved joint score tests, namely iAW.Lev, iAW.BF, and iAW.TM, and have made extensive comparisons with the joint likelihood ratio test (jointLRT), the Kolmogorov-Smirnov (KS) test, and the AW test. Systematic simulation studies showed that: 1) the three improved tests performed better (i.e., having larger power, while keeping nominal Type I error rates) than the other three tests for data with outliers and having different variances between cases and controls; 2) for data from normal distributions, the three improved tests had slightly lower power than jointLRT and AW. The analyses of two Illumina HumanMethylation27 data sets GSE37020 and GSE20080 and one Illumina Infinium MethylationEPIC data set GSE107080 demonstrated that three improved tests had higher true validation rates than those from jointLRT, KS, and AW.

CONCLUSIONS: The three proposed joint score tests are robust against the violation of normality assumption and presence of outlying observations in comparison with other three existing tests. Among the three proposed tests, iAW.BF seems to be the most robust and effective one for all simulated scenarios and also in real data analyses.}, } @article {pmid29776329, year = {2018}, author = {Larsen, SJ and do Canto, LM and Rogatto, SR and Baumbach, J}, title = {CoNVaQ: a web tool for copy number variation-based association studies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {369}, pmid = {29776329}, issn = {1471-2164}, support = {13154//Villum Fonden/ ; }, mesh = {*DNA Copy Number Variations ; Data Mining ; Genome-Wide Association Study/*methods ; *Internet ; *Software ; }, abstract = {BACKGROUND: Copy number variations (CNVs) are large segments of the genome that are duplicated or deleted. Structural variations in the genome have been linked to many complex diseases. Similar to how genome-wide association studies (GWAS) have helped discover single-nucleotide polymorphisms linked to disease phenotypes, the extension of GWAS to CNVs has aided the discovery of structural variants associated with human traits and diseases.

RESULTS: We present CoNVaQ, an easy-to-use web-based tool for CNV-based association studies. The web service allows users to upload two sets of CNV segments and search for genomic regions where the occurrence of CNVs is significantly associated with the phenotype. CoNVaQ provides two models: a simple statistical model using Fisher's exact test and a novel query-based model matching regions to user-defined queries. For each region, the method computes a global q-value statistic by repeated permutation of samples among the populations. We demonstrate our platform by using it to analyze a data set of HPV-positive and HPV-negative penile cancer patients.

CONCLUSIONS: CoNVaQ provides a simple workflow for performing CNV-based association studies. It is made available as a web platform in order to provide a user-friendly workflow for biologists and clinicians to carry out CNV data analysis without installing any software. Through the web interface, users are also able to analyze their results to find overrepresented GO terms and pathways. In addition, our method is also available as a package for the R programming language. CoNVaQ is available at https://convaq.compbio.sdu.dk .}, } @article {pmid29775177, year = {2018}, author = {Sheu, SY and Huang, CW and Chen, JC and Chen, ZH and Chen, WM}, title = {Novosphingobium arvoryzae sp. nov., isolated from a flooded rice field.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2151-2157}, doi = {10.1099/ijsem.0.002756}, pmid = {29775177}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Oryza/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Spermidine/chemistry ; Sphingomonadaceae/*classification/genetics/isolation & purification ; Taiwan ; }, abstract = {A bacterial strain, designated Jyi-02T, was isolated from a flooded rice field in Taiwan and characterized using the polyphasic taxonomy approach. Cells of strain Jyi-02T were aerobic, Gram-stain-negative, rod-shaped, non-motile and formed yellowish orange coloured colonies. Growth occurred at 10-40 °C (optimum, 20 °C) and pH 5.0-9.0 (optimum, pH 7.0) and in the presence of 0-1.0 % NaCl (optimum, 0 %, w/v). The major fatty acids (>10 %) of strain Jyi-02T were C18 : 1ω7c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C14 : 0 2-OH. The polar lipid profile consisted of a mixture of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, phosphatidyldimethylethanolamine, sphingoglycolipid, an uncharacterized phospholipid and an uncharacterized lipid. The major polyamine was spermidine. The major isoprenoid quinone was Q-10. The DNA G+C content was 64.8 mol%. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Jyi-02T belonged to the genus Novosphingobium and had closest phylogenetic similarity to Novosphingobium soli CC-TPE-1T (97.8 %). The DNA-DNA relatedness of strain Jyi-02T with respect to valid published species of the genus Novosphingobium was less than 35 %. Phenotypic characteristics of the novel strain also differed from those of the closest related species of the genus Novosphingobium. On the basis of the genotypic, chemotaxonomic and phenotypic data, strain Jyi-02T represents a novel species in the genus Novosphingobium, for which the name Novosphingobium arvoryzae sp. nov. is proposed. The type strain is Jyi-02T (=BCRC 80537T=KCTC 32422T).}, } @article {pmid29775176, year = {2018}, author = {Lv, YY and Zhang, XJ and Li, AZ and Zou, WL and Feng, GD and Zhu, HH}, title = {Chitinophaga varians sp. nov., isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2139-2144}, doi = {10.1099/ijsem.0.002700}, pmid = {29775176}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile bacterium, designated strain 10-7W-9003T, was isolated from the forest soil of Limushan National Forest Park, south-east China (19° 10' 42″ N, 109° 44' 45″ E). Strain 10-7W-9003T showed a shape change during the course of culture from long filamentous cells (5-10×0.4-0.5 µm) at 5-36 h, to rod shaped (1.0-1.5×0.5-0.7 µm) with inoculation after 2 days. It grew optimally at 28-30 °C and pH 6.5-7.5. On the basis of 16S rRNA gene sequence analysis, it belongs to the genus Chitinophaga and is most closely related to Chitinophaga eiseniae KACC 13774T and Chitinophaga qingshengii JCM 30026T, with 16S rRNA gene sequences similarities of 98.8 and 98.3 %, respectively. However, the DNA-DNA hybridization study showed that strain 10-7W-9003T shared relatively low relatedness values with KACC 13774T (21.8 %) and JCM 30026T (20.4 %), respectively. The major fatty acids (>10 %) were iso-C15 : 0, C16 : 1ω5c and iso-C17 : 0 3-OH. The genomic DNA G+C content was 50.7 mol%. It contained MK-7 as the major quinone. The phenotypic, chemotaxonomic and phylogenetic data clearly showed that strain 10-7W-9003T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga varians sp. nov. is proposed. The type strain is 10-7W-9003T (=GDMCC 1.1252T=KACC 19415T=KCTC 52926T).}, } @article {pmid29774945, year = {2018}, author = {Suni, SS and Hopkins, R}, title = {The relationship between postmating reproductive isolation and reinforcement in Phlox.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13507}, pmid = {29774945}, issn = {1558-5646}, abstract = {The process of speciation involves the accumulation of reproductive isolation (RI) between diverging lineages. Selection can favor increased RI via the process of reinforcement, whereby costs to hybridization impose selection for increased prezygotic RI. Reinforcement results in phenotypic divergence within at least one taxon, as a result of costly hybridization between sympatric taxa. The strength of selection driving reinforcement is determined by the cost of hybridization and the frequency of hybridization. We investigated the cost of hybridization by quantifying postmating RI barriers among Phlox species that comprise one of the best-studied cases of reinforcement. We determined if the strength of RI differs among lineages that have and have not undergone reinforcement, how much variability there is within species in RI, and whether RI is associated with phylogenetic relatedness. We found high RI for the species that underwent phenotypic divergence due to reinforcement; however, RI was also high between other species pairs. We found extensive variability in RI among individuals within species, and no evidence that the strength of RI was associated with phylogenetic relatedness. We suggest that phenotypic divergence due to reinforcement is associated with the frequency of hybridization and introgression, and not the cost of hybridization in this clade.}, } @article {pmid29774086, year = {2018}, author = {Luedin, SM and Pothier, JF and Danza, F and Storelli, N and Frigaard, NU and Wittwer, M and Tonolla, M}, title = {Complete genome sequence of "Thiodictyon syntrophicum" sp. nov. strain Cad16T, a photolithoautotrophic purple sulfur bacterium isolated from the alpine meromictic Lake Cadagno.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {14}, pmid = {29774086}, issn = {1944-3277}, abstract = {"Thiodictyon syntrophicum" sp. nov. strain Cad16T is a photoautotrophic purple sulfur bacterium belonging to the family of Chromatiaceae in the class of Gammaproteobacteria. The type strain Cad16T was isolated from the chemocline of the alpine meromictic Lake Cadagno in Switzerland. Strain Cad16T represents a key species within this sulfur-driven bacterial ecosystem with respect to carbon fixation. The 7.74-Mbp genome of strain Cad16T has been sequenced and annotated. It encodes 6237 predicted protein sequences and 59 RNA sequences. Phylogenetic comparison based on 16S rRNA revealed that Thiodictyon elegans strain DSM 232T the most closely related species. Genes involved in sulfur oxidation, central carbon metabolism and transmembrane transport were found. Noteworthy, clusters of genes encoding the photosynthetic machinery and pigment biosynthesis are found on the 0.48 Mb plasmid pTs485. We provide a detailed insight into the Cad16T genome and analyze it in the context of the microbial ecosystem of Lake Cadagno.}, } @article {pmid29773752, year = {2018}, author = {Wanchisen, BA}, title = {There's no shame in leaving.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {826}, doi = {10.1126/science.360.6390.826}, pmid = {29773752}, issn = {1095-9203}, } @article {pmid29773751, year = {2018}, author = {Warren, R and Price, J and Graham, E and Forstenhaeusler, N and VanDerWal, J}, title = {The projected effect on insects, vertebrates, and plants of limiting global warming to 1.5°C rather than 2°C.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {791-795}, doi = {10.1126/science.aar3646}, pmid = {29773751}, issn = {1095-9203}, mesh = {Animals ; *Extinction, Biological ; *Global Warming ; Hot Temperature ; *Insecta ; *Plants ; United Nations ; *Vertebrates ; }, abstract = {In the Paris Agreement on Climate Change, the United Nations is pursuing efforts to limit global warming to 1.5°C, whereas earlier aspirations focused on a 2°C limit. With current pledges, corresponding to ~3.2°C warming, climatically determined geographic range losses of >50% are projected in ~49% of insects, 44% of plants, and 26% of vertebrates. At 2°C, this falls to 18% of insects, 16% of plants, and 8% of vertebrates and at 1.5°C, to 6% of insects, 8% of plants, and 4% of vertebrates. When warming is limited to 1.5°C as compared with 2°C, numbers of species projected to lose >50% of their range are reduced by ~66% in insects and by ~50% in plants and vertebrates.}, } @article {pmid29773750, year = {2018}, author = {Jones, KR and Venter, O and Fuller, RA and Allan, JR and Maxwell, SL and Negret, PJ and Watson, JEM}, title = {One-third of global protected land is under intense human pressure.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {788-791}, doi = {10.1126/science.aap9565}, pmid = {29773750}, issn = {1095-9203}, mesh = {*Biodiversity ; *Conservation of Natural Resources ; *Human Activities ; Humans ; }, abstract = {In an era of massive biodiversity loss, the greatest conservation success story has been the growth of protected land globally. Protected areas are the primary defense against biodiversity loss, but extensive human activity within their boundaries can undermine this. Using the most comprehensive global map of human pressure, we show that 6 million square kilometers (32.8%) of protected land is under intense human pressure. For protected areas designated before the Convention on Biological Diversity was ratified in 1992, 55% have since experienced human pressure increases. These increases were lowest in large, strict protected areas, showing that they are potentially effective, at least in some nations. Transparent reporting on human pressure within protected areas is now critical, as are global targets aimed at efforts required to halt biodiversity loss.}, } @article {pmid29773749, year = {2018}, author = {Dinh, CT and Burdyny, T and Kibria, MG and Seifitokaldani, A and Gabardo, CM and García de Arquer, FP and Kiani, A and Edwards, JP and De Luna, P and Bushuyev, OS and Zou, C and Quintero-Bermudez, R and Pang, Y and Sinton, D and Sargent, EH}, title = {CO2 electroreduction to ethylene via hydroxide-mediated copper catalysis at an abrupt interface.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {783-787}, doi = {10.1126/science.aas9100}, pmid = {29773749}, issn = {1095-9203}, abstract = {Carbon dioxide (CO2) electroreduction could provide a useful source of ethylene, but low conversion efficiency, low production rates, and low catalyst stability limit current systems. Here we report that a copper electrocatalyst at an abrupt reaction interface in an alkaline electrolyte reduces CO2 to ethylene with 70% faradaic efficiency at a potential of -0.55 volts versus a reversible hydrogen electrode (RHE). Hydroxide ions on or near the copper surface lower the CO2 reduction and carbon monoxide (CO)-CO coupling activation energy barriers; as a result, onset of ethylene evolution at -0.165 volts versus an RHE in 10 molar potassium hydroxide occurs almost simultaneously with CO production. Operational stability was enhanced via the introduction of a polymer-based gas diffusion layer that sandwiches the reaction interface between separate hydrophobic and conductive supports, providing constant ethylene selectivity for an initial 150 operating hours.}, } @article {pmid29773748, year = {2018}, author = {Chang, C and Wu, M and He, D and Pei, Y and Wu, CF and Wu, X and Yu, H and Zhu, F and Wang, K and Chen, Y and Huang, L and Li, JF and He, J and Zhao, LD}, title = {3D charge and 2D phonon transports leading to high out-of-plane ZT in n-type SnSe crystals.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {778-783}, doi = {10.1126/science.aaq1479}, pmid = {29773748}, issn = {1095-9203}, abstract = {Thermoelectric technology enables the harvest of waste heat and its direct conversion into electricity. The conversion efficiency is determined by the materials figure of merit ZT Here we show a maximum ZT of ~2.8 ± 0.5 at 773 kelvin in n-type tin selenide (SnSe) crystals out of plane. The thermal conductivity in layered SnSe crystals is the lowest in the out-of-plane direction [two-dimensional (2D) phonon transport]. We doped SnSe with bromine to make n-type SnSe crystals with the overlapping interlayer charge density (3D charge transport). A continuous phase transition increases the symmetry and diverges two converged conduction bands. These two factors improve carrier mobility, while preserving a large Seebeck coefficient. Our findings can be applied in 2D layered materials and provide a new strategy to enhance out-of-plane electrical transport properties without degrading thermal properties.}, } @article {pmid29773747, year = {2018}, author = {Oshima, Y and Nakamura, A and Matsunaga, K}, title = {Extraordinary plasticity of an inorganic semiconductor in darkness.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {772-774}, doi = {10.1126/science.aar6035}, pmid = {29773747}, issn = {1095-9203}, abstract = {Inorganic semiconductors generally tend to fail in a brittle manner. Here, we report that extraordinary "plasticity" can take place in an inorganic semiconductor if the deformation is carried out "in complete darkness." Room-temperature deformation tests of zinc sulfide (ZnS) were performed under varying light conditions. ZnS crystals immediately fractured when they deformed under light irradiation. In contrast, it was found that ZnS crystals can be plastically deformed up to a deformation strain of εt = 45% in complete darkness. In addition, the optical bandgap of the deformed ZnS crystals was distinctly decreased after deformation. These results suggest that dislocations in ZnS become mobile in complete darkness and that multiplied dislocations can affect the optical bandgap over the whole crystal. Inorganic semiconductors are not necessarily intrinsically brittle.}, } @article {pmid29773746, year = {2018}, author = {Mundoor, H and Park, S and Senyuk, B and Wensink, HH and Smalyukh, II}, title = {Hybrid molecular-colloidal liquid crystals.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {768-771}, doi = {10.1126/science.aap9359}, pmid = {29773746}, issn = {1095-9203}, abstract = {Order and fluidity often coexist, with examples ranging from biological membranes to liquid crystals, but the symmetry of these soft-matter systems is typically higher than that of the constituent building blocks. We dispersed micrometer-long inorganic colloidal rods in a nematic liquid crystalline fluid of molecular rods. Both types of uniaxial building blocks, while freely diffusing, interact to form an orthorhombic nematic fluid, in which like-sized rods are roughly parallel to each other and the molecular ordering direction is orthogonal to that of colloidal rods. A coarse-grained model explains the experimental temperature-concentration phase diagram with one biaxial and two uniaxial nematic phases, as well as the orientational distributions of rods. Displaying properties of biaxial optical crystals, these hybrid molecular-colloidal fluids can be switched by electric and magnetic fields.}, } @article {pmid29773745, year = {2018}, author = {Atashgahi, S and Sánchez-Andrea, I and Heipieper, HJ and van der Meer, JR and Stams, AJM and Smidt, H}, title = {Prospects for harnessing biocide resistance for bioremediation and detoxification.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {743-746}, doi = {10.1126/science.aar3778}, pmid = {29773745}, issn = {1095-9203}, mesh = {Bacteria/drug effects/genetics/*metabolism ; *Biodegradation, Environmental ; Disinfectants/*adverse effects/pharmacology ; *Drug Resistance, Microbial/genetics ; Petroleum ; *Selection, Genetic ; }, abstract = {Prokaryotes in natural environments respond rapidly to high concentrations of chemicals and physical stresses. Exposure to anthropogenic toxic substances-such as oil, chlorinated solvents, or antibiotics-favors the evolution of resistant phenotypes, some of which can use contaminants as an exclusive carbon source or as electron donors and acceptors. Microorganisms similarly adapt to extreme pH, metal, or osmotic stress. The metabolic plasticity of prokaryotes can thus be harnessed for bioremediation and can be exploited in a variety of ways, ranging from stimulated natural attenuation to bioaugmentation and from wastewater treatment to habitat restoration.}, } @article {pmid29773744, year = {2018}, author = {Fisher, MC and Hawkins, NJ and Sanglard, D and Gurr, SJ}, title = {Worldwide emergence of resistance to antifungal drugs challenges human health and food security.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {739-742}, doi = {10.1126/science.aap7999}, pmid = {29773744}, issn = {1095-9203}, mesh = {Antifungal Agents/*adverse effects/therapeutic use ; Drug Resistance, Fungal/*genetics ; Evolution, Molecular ; *Food Supply ; *Fungi/drug effects/genetics/pathogenicity ; Humans ; Infection Control/*methods ; Mycoses/*drug therapy/microbiology/prevention & control ; }, abstract = {The recent rate of emergence of pathogenic fungi that are resistant to the limited number of commonly used antifungal agents is unprecedented. The azoles, for example, are used not only for human and animal health care and crop protection but also in antifouling coatings and timber preservation. The ubiquity and multiple uses of azoles have hastened the independent evolution of resistance in many environments. One consequence is an increasing risk in human health care from naturally occurring opportunistic fungal pathogens that have acquired resistance to this broad class of chemicals. To avoid a global collapse in our ability to control fungal infections and to avoid critical failures in medicine and food security, we must improve our stewardship of extant chemicals, promote new antifungal discovery, and leverage emerging technologies for alternative solutions.}, } @article {pmid29773743, year = {2018}, author = {Baker, S and Thomson, N and Weill, FX and Holt, KE}, title = {Genomic insights into the emergence and spread of antimicrobial-resistant bacterial pathogens.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {733-738}, doi = {10.1126/science.aar3777}, pmid = {29773743}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Anti-Bacterial Agents/*adverse effects/therapeutic use ; *Bacteria/drug effects/genetics/pathogenicity ; Community-Acquired Infections/drug therapy/microbiology ; Drug Resistance, Bacterial/*genetics ; Evolution, Molecular ; Foodborne Diseases/drug therapy/microbiology ; Genome, Bacterial ; Genomics ; Humans ; Methicillin-Resistant Staphylococcus aureus/genetics ; Sexually Transmitted Diseases/drug therapy/microbiology ; Whole Genome Sequencing ; }, abstract = {Whole-genome sequencing (WGS) has been vital for revealing the rapid temporal and spatial evolution of antimicrobial resistance (AMR) in bacterial pathogens. Some antimicrobial-resistant pathogens have outpaced us, with untreatable infections appearing in hospitals and the community. However, WGS has additionally provided us with enough knowledge to initiate countermeasures. Although we cannot stop bacterial adaptation, the predictability of many evolutionary processes in AMR bacteria offers us an opportunity to channel them using new control strategies. Furthermore, by using WGS for coordinating surveillance and to create a more fundamental understanding of the outcome of antimicrobial treatment and AMR mechanisms, we can use current and future antimicrobials more effectively and aim to extend their longevity.}, } @article {pmid29773742, year = {2018}, author = {Gould, F and Brown, ZS and Kuzma, J}, title = {Wicked evolution: Can we address the sociobiological dilemma of pesticide resistance?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {728-732}, doi = {10.1126/science.aar3780}, pmid = {29773742}, issn = {1095-9203}, mesh = {Agriculture/economics ; Animals ; Arthropods/drug effects/genetics ; Crops, Agricultural/microbiology/parasitology ; *Drug Resistance ; *Herbicides ; *Insecticides ; Pest Control/*economics/*methods ; Plant Weeds/drug effects/genetics ; }, abstract = {Resistance to insecticides and herbicides has cost billions of U.S. dollars in the agricultural sector and could result in millions of lives lost to insect-vectored diseases. We mostly continue to use pesticides as if resistance is a temporary issue that will be addressed by commercialization of new pesticides with novel modes of action. However, current evidence suggests that insect and weed evolution may outstrip our ability to replace outmoded chemicals and other control mechanisms. To avoid this outcome, we must address the mix of ecological, genetic, economic, and sociopolitical factors that prevent implementation of sustainable pest management practices. We offer an ambitious proposition.}, } @article {pmid29773741, year = {2018}, author = {Ash, C}, title = {Meeting resistance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {726-727}, doi = {10.1126/science.360.6390.726}, pmid = {29773741}, issn = {1095-9203}, mesh = {Anti-Bacterial Agents/*adverse effects ; *Drug Resistance ; Herbicides/*adverse effects ; Insecticides/*adverse effects ; }, } @article {pmid29773740, year = {2018}, author = {Roxburgh, M}, title = {Sharing chemistry with Māori students.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {724}, doi = {10.1126/science.aat6040}, pmid = {29773740}, issn = {1095-9203}, } @article {pmid29773739, year = {2018}, author = {Magris, RA and Pressey, RL}, title = {Marine protected areas: Just for show?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {723-724}, doi = {10.1126/science.aat6215}, pmid = {29773739}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; Brazil ; *Conservation of Natural Resources ; *Fishes ; *Oceans and Seas ; }, } @article {pmid29773738, year = {2018}, author = {Cramp, JE and Simpfendorfer, CA and Pressey, RL}, title = {Beware silent waning of shark protection.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {723}, doi = {10.1126/science.aat3089}, pmid = {29773738}, issn = {1095-9203}, mesh = {Animals ; Conservation of Natural Resources/*legislation & jurisprudence ; Fisheries ; Micronesia ; *Sharks ; }, } @article {pmid29773737, year = {2018}, author = {Alberts, B and Hyman, T and Pickett, CL and Tilghman, S and Varmus, H}, title = {Improving support for young biomedical scientists.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {716-718}, doi = {10.1126/science.aar8405}, pmid = {29773737}, issn = {1095-9203}, mesh = {*Biomedical Research/trends ; *Career Mobility ; European Union ; Financing, Organized ; Humans ; Research Personnel/*economics ; United States ; Workforce ; }, } @article {pmid29773736, year = {2018}, author = {Midgley, G}, title = {Narrowing pathways to a sustainable future.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {714-715}, doi = {10.1126/science.aat6671}, pmid = {29773736}, issn = {1095-9203}, mesh = {Climate Change ; *Conservation of Natural Resources ; *Forecasting ; Humans ; }, } @article {pmid29773735, year = {2018}, author = {Sabò, A and Amati, B}, title = {BRD4 and MYC-clarifying regulatory specificity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {713-714}, doi = {10.1126/science.aat6664}, pmid = {29773735}, issn = {1095-9203}, mesh = {Cell Line, Tumor ; Cell Proliferation ; Humans ; *Nuclear Proteins ; *Proto-Oncogene Proteins c-myc ; Transcription Factors ; }, } @article {pmid29773734, year = {2018}, author = {Poulin, P}, title = {How to achieve a successful biaxial marriage.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {712-713}, doi = {10.1126/science.aat7399}, pmid = {29773734}, issn = {1095-9203}, mesh = {Crystallization ; Humans ; *Stress, Mechanical ; }, } @article {pmid29773733, year = {2018}, author = {Nofal, M and Rabinowitz, JD}, title = {Ribosomes on the night shift.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {710-711}, doi = {10.1126/science.aat7121}, pmid = {29773733}, issn = {1095-9203}, mesh = {Humans ; *Ribosomes ; Risk Factors ; Starvation ; }, } @article {pmid29773732, year = {2018}, author = {Humphreys, BD}, title = {Mapping kidney cellular complexity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {709-710}, doi = {10.1126/science.aat7271}, pmid = {29773732}, issn = {1095-9203}, mesh = {*Epithelial Cells ; Humans ; *Kidney ; }, } @article {pmid29773731, year = {2018}, author = {Ager, JW and Lapkin, AA}, title = {Chemical storage of renewable energy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {707-708}, doi = {10.1126/science.aat7918}, pmid = {29773731}, issn = {1095-9203}, mesh = {*Renewable Energy ; }, } @article {pmid29773730, year = {2018}, author = {Eichler, A}, title = {Little is lost.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {706-707}, doi = {10.1126/science.aat1983}, pmid = {29773730}, issn = {1095-9203}, } @article {pmid29773729, year = {2018}, author = {Gibbons, A}, title = {Hadza on the brink.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {700-704}, doi = {10.1126/science.360.6390.700}, pmid = {29773729}, issn = {1095-9203}, } @article {pmid29773728, year = {2018}, author = {Hutson, M}, title = {Boycott highlights AI's publishing rebellion.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {699}, doi = {10.1126/science.360.6390.699}, pmid = {29773728}, issn = {1095-9203}, } @article {pmid29773727, year = {2018}, author = {Clery, D}, title = {China's moon mission is set to probe cosmic dark ages.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {698}, doi = {10.1126/science.360.6390.698}, pmid = {29773727}, issn = {1095-9203}, } @article {pmid29773726, year = {2018}, author = {Cho, A}, title = {Neutron stars' quark matter not so strange.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {697}, doi = {10.1126/science.360.6390.697}, pmid = {29773726}, issn = {1095-9203}, } @article {pmid29773725, year = {2018}, author = {Pennisi, E}, title = {High altitude may have driven short stature in Peruvians.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {696}, doi = {10.1126/science.360.6390.696}, pmid = {29773725}, issn = {1095-9203}, mesh = {Alleles ; *Altitude ; Body Height/*genetics ; Fibrillin-1/*genetics ; *Gene-Environment Interaction ; Genetic Variation ; Humans ; Peru ; }, } @article {pmid29773724, year = {2018}, author = {Servick, K}, title = {U.S. lawmakers float plan to regulate cultured meat.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {695}, doi = {10.1126/science.360.6390.695}, pmid = {29773724}, issn = {1095-9203}, mesh = {Animals ; Bioreactors ; Biotechnology/*legislation & jurisprudence ; *Cell Culture Techniques ; *Meat ; United States ; United States Department of Agriculture/*legislation & jurisprudence ; }, } @article {pmid29773723, year = {2018}, author = {Cohen, J}, title = {Vaccine trial launched to stop Ebola.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {694-695}, doi = {10.1126/science.360.6390.694}, pmid = {29773723}, issn = {1095-9203}, mesh = {Clinical Trials as Topic ; Congo/epidemiology ; Disease Outbreaks/*prevention & control ; Ebola Vaccines/immunology/*therapeutic use ; Ebolavirus/immunology ; Hemorrhagic Fever, Ebola/*epidemiology/*prevention & control ; Humans ; World Health Organization ; }, } @article {pmid29773722, year = {2018}, author = {Reese, A}, title = {Drilling threatens ancient Chaco landscape.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {693-694}, doi = {10.1126/science.360.6390.693}, pmid = {29773722}, issn = {1095-9203}, } @article {pmid29773721, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {690-692}, doi = {10.1126/science.360.6390.690}, pmid = {29773721}, issn = {1095-9203}, } @article {pmid29773720, year = {2018}, author = {Costello, TJ}, title = {NextGen postdocs.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {689}, doi = {10.1126/science.aau1303}, pmid = {29773720}, issn = {1095-9203}, mesh = {*Behavioral Research/economics/education ; *Biomedical Research/economics/education ; Research Personnel ; United States ; Workforce ; }, } @article {pmid29773719, year = {2018}, author = {Kim, KH and Späh, A and Pathak, H and Perakis, F and Mariedahl, D and Amann-Winkel, K and Sellberg, JA and Lee, JH and Kim, S and Park, J and Nam, KH and Katayama, T and Nilsson, A}, title = {Response to Comment on "Maxima in the thermodynamic response and correlation functions of deeply supercooled water".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {}, doi = {10.1126/science.aat1729}, pmid = {29773719}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {*Thermodynamics ; *Water ; }, abstract = {Caupin et al have raised several issues regarding our recent paper on maxima in thermodynamic response and correlation functions in deeply supercooled water. We show that these issues can be addressed without affecting the conclusion of the paper.}, } @article {pmid29773718, year = {2018}, author = {Caupin, F and Holten, V and Qiu, C and Guillerm, E and Wilke, M and Frenz, M and Teixeira, J and Soper, AK}, title = {Comment on "Maxima in the thermodynamic response and correlation functions of deeply supercooled water".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {}, doi = {10.1126/science.aat1634}, pmid = {29773718}, issn = {1095-9203}, abstract = {Kim et al recently measured the structure factor of deeply supercooled water droplets (Reports, 22 December 2017, p. 1589). We raise several concerns about their data analysis and interpretation. In our opinion, the reported data do not lead to clear conclusions about the origins of water's anomalies.}, } @article {pmid29773710, year = {2018}, author = {Albrecht, LV and Ploper, D and Tejeda-Muñoz, N and De Robertis, EM}, title = {Arginine methylation is required for canonical Wnt signaling and endolysosomal trafficking.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5317-E5325}, doi = {10.1073/pnas.1804091115}, pmid = {29773710}, issn = {1091-6490}, support = {F32 GM123622/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arginine/*metabolism ; Cell Line ; Endocytosis/physiology ; Endosomes/metabolism ; Glycogen Synthase Kinase 3/metabolism ; Humans ; Intercellular Signaling Peptides and Proteins/metabolism ; Lysosomes/metabolism ; Methylation ; Multivesicular Bodies/metabolism ; Phosphorylation ; Protein Processing, Post-Translational ; Protein Transport ; Protein-Arginine N-Methyltransferases/*metabolism/physiology ; Repressor Proteins/*metabolism/physiology ; Smad4 Protein ; Ubiquitination ; Wnt Proteins/metabolism ; Wnt Signaling Pathway/*physiology ; }, abstract = {Arginine methylation has emerged as a widespread and reversible protein modification with the potential to regulate a multitude of cellular processes, but its function is poorly understood. Endolysosomes play an important role in Wnt signaling, in which glycogen synthase kinase 3 (GSK3) becomes sequestered inside multivesicular bodies (MVBs) by the process known as microautophagy, causing the stabilization of many proteins. Up to 20% of cellular proteins contain three or more consecutive putative GSK3 sites, and of these 33% also contain methylarginine (meArg) modifications. Intriguingly, a cytoskeletal protein was previously known to have meArg modifications that enhanced subsequent phosphorylations by GSK3. Here, we report the unexpected finding that protein arginine methyltransferase 1 (PRMT1) is required for canonical Wnt signaling. Treatment of cultured cells for 5-30 min with Wnt3a induced a large increase in total endocytic vesicles which were also positive for asymmetric dimethylarginine modifications. Protease protection studies, both biochemical and in situ in cultured cells, showed that many meArg-modified cytosolic proteins became rapidly translocated into MVBs together with GSK3 and Lys48-polyubiquitinated proteins by ESCRT-driven microautophagy. In the case of the transcription factor Smad4, we showed that a unique arginine methylation site was required for GSK3 phosphorylation and Wnt regulation. The enzyme PRMT1 was found to be essential for Wnt-stimulated arginine methylation, GSK3 sequestration, and canonical Wnt signaling. The results reveal a cell biological role for PRMT1 arginine methylation at the crossroads of growth factor signaling, protein phosphorylation, membrane trafficking, cytosolic proteolysis, and Wnt-regulated microautophagy.}, } @article {pmid29773709, year = {2018}, author = {Yu, T and Wu, W and Liang, W and Lever, MA and Hinrichs, KU and Wang, F}, title = {Growth of sedimentary Bathyarchaeota on lignin as an energy source.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6022-6027}, pmid = {29773709}, issn = {1091-6490}, mesh = {Archaea/metabolism ; Carbon/metabolism ; Chemoautotrophic Growth/physiology ; DNA, Archaeal/metabolism ; Energy-Generating Resources ; Geologic Sediments/*chemistry/*microbiology ; Lignin/chemistry/*metabolism ; Methane/metabolism ; RNA, Ribosomal, 16S/metabolism ; }, abstract = {Members of the archaeal phylum Bathyarchaeota are among the most abundant microorganisms on Earth. Although versatile metabolic capabilities such as acetogenesis, methanogenesis, and fermentation have been suggested for bathyarchaeotal members, no direct confirmation of these metabolic functions has been achieved through growth of Bathyarchaeota in the laboratory. Here we demonstrate, on the basis of gene-copy numbers and probing of archaeal lipids, the growth of Bathyarchaeota subgroup Bathy-8 in enrichments of estuarine sediments with the biopolymer lignin. Other organic substrates (casein, oleic acid, cellulose, and phenol) did not significantly stimulate growth of Bathyarchaeota Meanwhile, putative bathyarchaeotal tetraether lipids incorporated 13C from 13C-bicarbonate only when added in concert with lignin. Our results are consistent with organoautotrophic growth of a bathyarchaeotal group with lignin as an energy source and bicarbonate as a carbon source and shed light into the cycling of one of Earth's most abundant biopolymers in anoxic marine sediment.}, } @article {pmid29773708, year = {2018}, author = {Joost, M and Nava, M and Transue, WJ and Martin-Drumel, MA and McCarthy, MC and Patterson, D and Cummins, CC}, title = {Sulfur monoxide thermal release from an anthracene-based precursor, spectroscopic identification, and transfer reactivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5866-5871}, pmid = {29773708}, issn = {1091-6490}, abstract = {Sulfur monoxide (SO) is a highly reactive molecule and thus, eludes bulk isolation. We report here on synthesis and reactivity of a molecular precursor for SO generation, namely 7-sulfinylamino-7-azadibenzonorbornadiene (1). This compound has been shown to fragment readily driven by dinitrogen expulsion and anthracene formation on heating in the solid state and in solution, releasing SO at mild temperatures (<100 °C). The generated SO was detected in the gas phase by MS and rotational spectroscopy. In solution, 1 allows for SO transfer to organic molecules as well as transition metal complexes.}, } @article {pmid29773669, year = {2018}, author = {Pommier, A and Anaparthy, N and Memos, N and Kelley, ZL and Gouronnec, A and Yan, R and Auffray, C and Albrengues, J and Egeblad, M and Iacobuzio-Donahue, CA and Lyons, SK and Fearon, DT}, title = {Unresolved endoplasmic reticulum stress engenders immune-resistant, latent pancreatic cancer metastases.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {}, doi = {10.1126/science.aao4908}, pmid = {29773669}, issn = {1095-9203}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Pancreatic Ductal/immunology/*secondary ; Endoplasmic Reticulum Stress/*immunology ; Endoribonucleases/genetics/metabolism ; Genes, MHC Class I ; Genetic Engineering ; Humans ; Keratin-19/metabolism ; Liver Neoplasms/immunology/*secondary ; Lymphocyte Depletion ; Mice ; Mice, Inbred C57BL ; Neoplasms, Experimental/genetics/immunology/secondary ; Pancreatic Neoplasms/immunology/*pathology ; Protein-Serine-Threonine Kinases/genetics/metabolism ; T-Lymphocytes/immunology ; *Tumor Escape ; X-Box Binding Protein 1/genetics/metabolism ; }, abstract = {The majority of patients with pancreatic ductal adenocarcinoma (PDA) develop metastatic disease after resection of their primary tumor. We found that livers from patients and mice with PDA harbor single disseminated cancer cells (DCCs) lacking expression of cytokeratin 19 (CK19) and major histocompatibility complex class I (MHCI). We created a mouse model to determine how these DCCs develop. Intraportal injection of immunogenic PDA cells into preimmunized mice seeded livers only with single, nonreplicating DCCs that were CK19- and MHCI- The DCCs exhibited an endoplasmic reticulum (ER) stress response but paradoxically lacked both inositol-requiring enzyme 1α activation and expression of the spliced form of transcription factor XBP1 (XBP1s). Inducible expression of XBP1s in DCCs, in combination with T cell depletion, stimulated the outgrowth of macrometastatic lesions that expressed CK19 and MHCI. Thus, unresolved ER stress enables DCCs to escape immunity and establish latent metastases.}, } @article {pmid29773668, year = {2018}, author = {Cai, Q and Qiao, L and Wang, M and He, B and Lin, FM and Palmquist, J and Huang, SD and Jin, H}, title = {Plants send small RNAs in extracellular vesicles to fungal pathogen to silence virulence genes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {1126-1129}, doi = {10.1126/science.aar4142}, pmid = {29773668}, issn = {1095-9203}, support = {R01 GM093008/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*immunology/*microbiology ; Botrytis/genetics/*pathogenicity ; Extracellular Vesicles/metabolism ; *Host-Pathogen Interactions ; Plant Diseases/immunology/microbiology ; Plant Immunity ; *RNA Interference ; RNA, Plant/*metabolism ; RNA, Small Interfering/*metabolism ; Virulence/genetics ; Virulence Factors/genetics ; }, abstract = {Some pathogens and pests deliver small RNAs (sRNAs) into host cells to suppress host immunity. Conversely, hosts also transfer sRNAs into pathogens and pests to inhibit their virulence. Although sRNA trafficking has been observed in a wide variety of interactions, how sRNAs are transferred, especially from hosts to pathogens and pests, is still unknown. Here, we show that host Arabidopsis cells secrete exosome-like extracellular vesicles to deliver sRNAs into fungal pathogen Botrytis cinerea These sRNA-containing vesicles accumulate at the infection sites and are taken up by the fungal cells. Transferred host sRNAs induce silencing of fungal genes critical for pathogenicity. Thus, Arabidopsis has adapted exosome-mediated cross-kingdom RNA interference as part of its immune responses during the evolutionary arms race with the pathogen.}, } @article {pmid29773667, year = {2018}, author = {Chakrabarti, R and Celià-Terrassa, T and Kumar, S and Hang, X and Wei, Y and Choudhury, A and Hwang, J and Peng, J and Nixon, B and Grady, JJ and DeCoste, C and Gao, J and van Es, JH and Li, MO and Aifantis, I and Clevers, H and Kang, Y}, title = {Notch ligand Dll1 mediates cross-talk between mammary stem cells and the macrophageal niche.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {}, doi = {10.1126/science.aan4153}, pmid = {29773667}, issn = {1095-9203}, support = {R01 CA141062/CA/NCI NIH HHS/United States ; R01 CA198280/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; K22 CA193661/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Count ; Female ; Gene Knockout Techniques ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Ligands ; Macrophages/cytology/*physiology ; Mammary Glands, Animal/*cytology/*growth & development/metabolism ; Mice ; Mice, Knockout ; Morphogenesis ; Receptors, Notch/*metabolism ; Signal Transduction ; Stem Cell Niche/*physiology ; Stem Cells/cytology/*physiology ; Stromal Cells/cytology/physiology ; Wnt Proteins/metabolism ; }, abstract = {The stem cell niche is a specialized environment that dictates stem cell function during development and homeostasis. We show that Dll1, a Notch pathway ligand, is enriched in mammary gland stem cells (MaSCs) and mediates critical interactions with stromal macrophages in the surrounding niche in mouse models. Conditional deletion of Dll1 reduced the number of MaSCs and impaired ductal morphogenesis in the mammary gland. Moreover, MaSC-expressed Dll1 activates Notch signaling in stromal macrophages, increasing their expression of Wnt family ligands such as Wnt3, Wnt10A, and Wnt16, thereby initiating a feedback loop that promotes the function of Dll1-expressing MaSCs. Together, these findings reveal functionally important cross-talk between MaSCs and their macrophageal niche through Dll1-mediated Notch signaling.}, } @article {pmid29773666, year = {2018}, author = {Lipson, M and Cheronet, O and Mallick, S and Rohland, N and Oxenham, M and Pietrusewsky, M and Pryce, TO and Willis, A and Matsumura, H and Buckley, H and Domett, K and Nguyen, GH and Trinh, HH and Kyaw, AA and Win, TT and Pradier, B and Broomandkhoshbacht, N and Candilio, F and Changmai, P and Fernandes, D and Ferry, M and Gamarra, B and Harney, E and Kampuansai, J and Kutanan, W and Michel, M and Novak, M and Oppenheimer, J and Sirak, K and Stewardson, K and Zhang, Z and Flegontov, P and Pinhasi, R and Reich, D}, title = {Ancient genomes document multiple waves of migration in Southeast Asian prehistory.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6397}, pages = {92-95}, doi = {10.1126/science.aat3188}, pmid = {29773666}, issn = {1095-9203}, support = {R01 GM100233/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Agriculture/history ; Asia, Southeastern ; Asian Continental Ancestry Group/genetics ; DNA, Ancient ; Genetic Variation ; *Genome, Human ; History, Ancient ; Human Migration/*history ; Humans ; Language/*history ; Radiometric Dating ; }, abstract = {Southeast Asia is home to rich human genetic and linguistic diversity, but the details of past population movements in the region are not well known. Here, we report genome-wide ancient DNA data from 18 Southeast Asian individuals spanning from the Neolithic period through the Iron Age (4100 to 1700 years ago). Early farmers from Man Bac in Vietnam exhibit a mixture of East Asian (southern Chinese agriculturalist) and deeply diverged eastern Eurasian (hunter-gatherer) ancestry characteristic of Austroasiatic speakers, with similar ancestry as far south as Indonesia providing evidence for an expansive initial spread of Austroasiatic languages. By the Bronze Age, in a parallel pattern to Europe, sites in Vietnam and Myanmar show close connections to present-day majority groups, reflecting substantial additional influxes of migrants.}, } @article {pmid29773229, year = {2018}, author = {de la Torre, I and Mora, R}, title = {Oldowan technological behaviour at HWK EE (Olduvai Gorge, Tanzania).}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {236-273}, doi = {10.1016/j.jhevol.2018.04.001}, pmid = {29773229}, issn = {1095-8606}, abstract = {HWK EE (Olduvai Gorge, Tanzania) is a late Oldowan site dated to ∼1.7 Ma that contains a large fossil and lithic assemblage. This paper reports on the technology of the recently excavated stone tool collection, over 18,000 pieces. Our results indicate that reduction sequences were generally short, flaking productivity was low, and knapping methods were largely simple and expedient, lacking the technical skills observed in other Oldowan assemblages. Conspicuous differences are observed in the chaînes opératoires of the three main raw materials used at HWK EE: the quartzite reduction sequence can be reconstructed in full at the site, most of the lava detached pieces are missing, and there is a preferential use of chert for retouched tools. This portrays a composite picture, where knapping expediency and low productivity are accompanied by raw material selectivity and consistent presence of retouched artefacts. Coexistence of these features in the same assemblage leads us to question the monolithic structure of the Oldowan techno-complex, and highlights the kaleidoscopic nature of technological strategies at Olduvai immediately before the earliest Acheulean handaxes appear in the sequence.}, } @article {pmid29773223, year = {2018}, author = {Gutzman, JH and Sahu, SU and Kwas, C}, title = {Corrigendum to 'Non-muscle myosin IIA and IIB differentially regulate cell shape changes during zebrafish brain morphogenesis' [Dev. Biol. 397 (2015) 103-115>].}, journal = {Developmental biology}, volume = {441}, number = {1}, pages = {204}, doi = {10.1016/j.ydbio.2018.05.001}, pmid = {29773223}, issn = {1095-564X}, } @article {pmid29773078, year = {2018}, author = {Bokulich, NA and Kaehler, BD and Rideout, JR and Dillon, M and Bolyen, E and Knight, R and Huttley, GA and Gregory Caporaso, J}, title = {Optimizing taxonomic classification of marker-gene amplicon sequences with QIIME 2's q2-feature-classifier plugin.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {90}, pmid = {29773078}, issn = {2049-2618}, support = {U54 CA143924/CA/NCI NIH HHS/United States ; U54 CA143925/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Bacteria/*genetics ; Base Sequence/genetics ; *Computer Simulation ; DNA, Intergenic/*genetics ; Fungi/*genetics ; Machine Learning ; Microbiota/*genetics ; RNA, Ribosomal, 16S/*genetics ; Sequence Alignment/*methods ; Software ; }, abstract = {BACKGROUND: Taxonomic classification of marker-gene sequences is an important step in microbiome analysis.

RESULTS: We present q2-feature-classifier (https://github.com/qiime2/q2-feature-classifier), a QIIME 2 plugin containing several novel machine-learning and alignment-based methods for taxonomy classification. We evaluated and optimized several commonly used classification methods implemented in QIIME 1 (RDP, BLAST, UCLUST, and SortMeRNA) and several new methods implemented in QIIME 2 (a scikit-learn naive Bayes machine-learning classifier, and alignment-based taxonomy consensus methods based on VSEARCH, and BLAST+) for classification of bacterial 16S rRNA and fungal ITS marker-gene amplicon sequence data. The naive-Bayes, BLAST+-based, and VSEARCH-based classifiers implemented in QIIME 2 meet or exceed the species-level accuracy of other commonly used methods designed for classification of marker gene sequences that were evaluated in this work. These evaluations, based on 19 mock communities and error-free sequence simulations, including classification of simulated "novel" marker-gene sequences, are available in our extensible benchmarking framework, tax-credit (https://github.com/caporaso-lab/tax-credit-data).

CONCLUSIONS: Our results illustrate the importance of parameter tuning for optimizing classifier performance, and we make recommendations regarding parameter choices for these classifiers under a range of standard operating conditions. q2-feature-classifier and tax-credit are both free, open-source, BSD-licensed packages available on GitHub.}, } @article {pmid29772349, year = {2018}, author = {Daniels, SR and Klaus, S}, title = {Divergent evolutionary origins and biogeographic histories of two freshwater crabs (Brachyura: Potamonautes) on the West African conveyer belt islands of São Tomé and Príncipe.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {119-128}, doi = {10.1016/j.ympev.2018.05.016}, pmid = {29772349}, issn = {1095-9513}, abstract = {We examined the colonization history and phylogeographic structure of the two endemic freshwater crab species (Potamonautes margaritarius and P. principe) inhabiting the volcanic islands of São Tomé and Príncipe, respectively, using mitochondrial and nuclear DNA sequence data. All samples were sequenced for the mtDNA COI locus and used in the phylogeographic analyses, while a single specimen per lineage was sequenced for the two remaining loci (16S rRNA and histone 3) and used in the phylogenetic reconstruction. Phylogenetic results reveal that P. principe diverged early within a clade of East/Southern African Potamonautes during the Miocene, while P. margaritarius diverged between the Late Eocene to Early Miocene. Furthermore, the two species are not sister taxa and are distantly related. These results corroborate previously hypothesised independent transoceanic dispersal events that resulted in the establishment of the endemic freshwater crab fauna of the two islands. Within P. margaritarius, we observed two reciprocally monophyletic clades on São Tomé Island. Clade one occurred in the southeast and southwest of the island, while clade two occurred in the northeast and the northwest; the divergence between the latter two clades was estimated to be of Pleistocene age. The two clades within P. margartarius are genetically highly structured and characterised by the absence of shared maternal haplotypes, suggesting possible speciation within P. margartarius. In contrast P. principe exhibits a shallow population genetic structure. Possible mechanisms of colonization and cladogenesis in the two freshwater crabs are discussed.}, } @article {pmid29772256, year = {2018}, author = {Atanasova, NS and Demina, TA and Krishnam Rajan Shanthi, SNV and Oksanen, HM and Bamford, DH}, title = {Extremely halophilic pleomorphic archaeal virus HRPV9 extends the diversity of pleolipoviruses with integrases.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {500-504}, doi = {10.1016/j.resmic.2018.04.004}, pmid = {29772256}, issn = {1769-7123}, mesh = {Archaeal Viruses/classification/*enzymology/*genetics/physiology ; DNA Viruses/genetics ; DNA, Viral/genetics ; Genome, Viral ; Integrases/*genetics ; Open Reading Frames ; Plasmids ; *Salinity ; Virion ; }, abstract = {Certain pleomorphic archaeal viruses are highly infectious even at saturated salt. These viruses belong to the genus Betapleolipovirus of the recently described archaeal virus family Pleolipoviridae. Pleolipoviruses comprise single-stranded or double-stranded, circular or linear DNA genomes that share countless homologues among various archaeal genetic elements. Here we describe a new extremely halophilic betapleolipovirus, Halorubrum pleomorphic virus 9 (HRPV9), which has an integrase gene. We also identified new genes encoding minor pleolipoviral structural proteins. The studies on HRPV9 enhance our knowledge on pleolipoviruses, especially their reciprocal relatedness and relation to certain archaeal plasmids, proviruses and membrane vesicles.}, } @article {pmid29772227, year = {2018}, author = {Lloyd, E and Olive, C and Stahl, BA and Jaggard, JB and Amaral, P and Duboué, ER and Keene, AC}, title = {Evolutionary shift towards lateral line dependent prey capture behavior in the blind Mexican cavefish.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {328-337}, doi = {10.1016/j.ydbio.2018.04.027}, pmid = {29772227}, issn = {1095-564X}, support = {R01 GM127872/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; Characiformes/*physiology ; Feeding Behavior/*physiology ; Lateral Line System/*physiology ; Predatory Behavior/*physiology ; }, abstract = {Feeding strategies are dependent on multi-modal sensory processing, that integrates visual, chemosensory, and mechanoreceptive cues. In many fish species, local environments and food availability dramatically influence the evolution of sensory and morphological traits that underlie feeding. The Mexican cavefish, Astyanax mexicanus, have developed robust changes in sensory-dependent behaviors, but the impact on prey detection and feeding behavior is not known. In the absence of eyes, cavefish have evolved enhanced sensitivity of the lateral line, comprised of mechanosensory organs that sense water flow and detect prey. Here, we identify evolved differences in prey capture behavior of larval cavefish that are dependent on lateral line sensitivity. Under lighted conditions, cavefish strike Artemia prey at a wider angle than surface fish; however, this difference is diminished under dark conditions. In addition, the strike distance is greater in cavefish than surface fish, revealing an ability to capture, and likely detect, prey at greater distances. Experimental ablation of the lateral line disrupts prey capture in cavefish under both light and dark conditions, while it only impacts surface fish under dark conditions. Together, these findings identify an evolutionary shift towards a dependence on the lateral line for prey capture in cavefish, providing a model for investigating how loss of visual cues impacts multi-modal sensory behaviors.}, } @article {pmid29771364, year = {2018}, author = {Kijpornyongpan, T and Mondo, SJ and Barry, K and Sandor, L and Lee, J and Lipzen, A and Pangilinan, J and LaButti, K and Hainaut, M and Henrissat, B and Grigoriev, IV and Spatafora, JW and Aime, MC}, title = {Broad Genomic Sampling Reveals a Smut Pathogenic Ancestry of the Fungal Clade Ustilaginomycotina.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1840-1854}, doi = {10.1093/molbev/msy072}, pmid = {29771364}, issn = {1537-1719}, abstract = {Ustilaginomycotina is home to a broad array of fungi including important plant pathogens collectively called smut fungi. Smuts are biotrophs that produce characteristic perennating propagules called teliospores, one of which, Ustilago maydis, is a model genetic organism. Broad exploration of smut biology has been hampered by limited phylogenetic resolution of Ustilaginiomycotina as well as an overall lack of genomic data for members of this subphylum. In this study, we sequenced eight Ustilaginomycotina genomes from previously unrepresented lineages, deciphered ordinal-level phylogenetic relationships for the subphylum, and performed comparative analyses. Unlike other Basidiomycota subphyla, all sampled Ustilaginomycotina genomes are relatively small and compact. Ancestral state reconstruction analyses indicate that teliospore formation was present at the origin of the subphylum. Divergence time estimation dates the divergence of most extant smut fungi after that of grasses (Poaceae). However, we found limited conservation of well-characterized genes related to smut pathogenesis from U. maydis, indicating dissimilar pathogenic mechanisms exist across other smut lineages. The genomes of Malasseziomycetes are highly diverged from the other sampled Ustilaginomycotina, likely due to their unique history as mammal-associated lipophilic yeasts. Despite extensive genomic data, the phylogenetic placement of this class remains ambiguous. Although the sampled Ustilaginomycotina members lack many core enzymes for plant cell wall decomposition and starch catabolism, we identified several novel carbohydrate active enzymes potentially related to pectin breakdown. Finally, ∼50% of Ustilaginomycotina species-specific genes are present in previously undersampled and rare lineages, highlighting the importance of exploring fungal diversity as a resource for novel gene discovery.}, } @article {pmid29771345, year = {2018}, author = {Yin, X and Heeney, DD and Srisengfa, YT and Chen, SY and Slupsky, CM and Marco, ML}, title = {Sucrose metabolism alters Lactobacillus plantarum survival and interactions with the microbiota in the digestive tract.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy084}, pmid = {29771345}, issn = {1574-6941}, abstract = {We investigated whether sucrose metabolism by probiotic Lactobacillus plantarum influences the intestinal survival and microbial responses to this organism when administered to mice fed a sucrose-rich, Western diet. A L. plantarum mutant unable to metabolize sucrose was constructed by deleting scrB, coding for beta-fructofuranosidase, in a rifampicin-resistant strain of L. plantarum NCIMB8826. The ScrB deficient mutant survived in 8-fold higher numbers compared to the wild-type strain when measured 24 h after administration on two consecutive days. According to 16S rRNA marker gene sequencing, proportions of Faecalibacterium and Streptococcus were elevated in mice fed the L. plantarum ΔscrB mutant. Metagenome predictions also indicated those mice contained a higher abundance of lactate dehydrogenases. This was further supported by a trend in elevated fecal lactate concentrations among mice fed the ΔscrB mutant. L. plantarum also caused other changes to the fecal metabolomes including higher concentrations of glycerol in mice fed the ΔscrB mutant and increased uracil, acetate and propionate levels among mice fed the wild-type strain. Taken together, these results suggest that sucrose metabolism alters the properties of L. plantarum in the digestive tract and that probiotics can differentially influence intestinal metabolomes via their carbohydrate consumption capabilities.}, } @article {pmid29771325, year = {2018}, author = {Armada, E and Leite, MFA and Medina, A and Azcón, R and Kuramae, EE}, title = {Native bacteria promote plant growth under drought stress condition without impacting the rhizomicrobiome.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy092}, pmid = {29771325}, issn = {1574-6941}, abstract = {Inoculation of plants with beneficial plant growth-promoting bacteria (PGPB) emerges a valuable strategy for ecosystem recovery. However, drought conditions might compromise plant-microbe interactions especially in semiarid regions. This study highlights the effect of native PGPB after 1 year inoculation on autochthonous shrubs growth and rhizosphere microbial community composition and activity under drought stress conditions. We inoculated three plant species of semiarid Mediterranean zones, Thymus vulgaris, Santolina chamaecyparissus and Lavandula dentata with a Bacillus thuringiensis strain IAM 12077 and evaluated the impact on plant biomass, plant nutrient contents, arbuscular mycorrhiza fungi (AMF) colonization, soil rhizosphere microbial activity and both the bacterial and fungal communities. Inoculation with strain IAM 12077 improved the ability of all three plants species to uptake nutrients from the soil, promoted L. dentata shoot growth (>65.8%), and doubled the AMF root colonization of S. chamaecyparissus. Inoculation did not change the rhizosphere microbial community. Moreover, changes in rhizosphere microbial activity were mainly plant species-specific and strongly associated with plant nutrients. In conclusion, the strain IAM 12077 induced positive effects on plant growth and nutrient acquisition with no impact on the rhizosphere microbiome, indicating a rhizosphere microbial community resilient to native bacteria inoculation.}, } @article {pmid29771319, year = {2018}, author = {Rousidou, C and Karaiskos, D and Myti, D and Karanasios, E and Karas, PA and Tourna, M and Tzortzakakis, EA and Karpouzas, DG}, title = {Distribution and function of carbamate hydrolase genes cehA and mcd in soils: the distinct role of soil pH.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy069}, pmid = {29771319}, issn = {1574-6941}, } @article {pmid29771318, year = {2018}, author = {Alonso, CA and Alcalá, L and Simón, C and Torres, C}, title = {Novel sequence types of extended-spectrum and acquired AmpC beta-lactamase producing Escherichia coli and Escherichia clade V isolated from wild mammals.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy066}, pmid = {29771318}, issn = {1574-6941}, } @article {pmid29769752, year = {2018}, author = {Godman, M}, title = {Gender as a historical kind: a tale of two genders?.}, journal = {Biology & philosophy}, volume = {33}, number = {3}, pages = {21}, pmid = {29769752}, issn = {0169-3867}, abstract = {Is there anything that members of each binary category of gender have in common? Even many non-essentialists find the lack of unity within a gender worrying as it undermines the basis for a common political agenda for women. One promising proposal for achieving unity is by means of a shared historical lineage of cultural reproduction with past binary models of gender (e.g. Bach in Ethics 122:231-272, 2012). I demonstrate how such an account is likely to take on board different binary and also non-binary systems of gender. This implies that all individuals construed as members of the category, "women" are in fact not members of the same historical kind after all! I then consider different possible means of modifying the account but conclude negatively: the problem runs deeper than has been appreciated thus far.}, } @article {pmid29769729, year = {2018}, author = {Liu, Y and Guo, J and Zhu, E and Liao, L and Lee, SJ and Ding, M and Shakir, I and Gambin, V and Huang, Y and Duan, X}, title = {Approaching the Schottky-Mott limit in van der Waals metal-semiconductor junctions.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {696-700}, doi = {10.1038/s41586-018-0129-8}, pmid = {29769729}, issn = {1476-4687}, abstract = {The junctions formed at the contact between metallic electrodes and semiconductor materials are crucial components of electronic and optoelectronic devices 1 . Metal-semiconductor junctions are characterized by an energy barrier known as the Schottky barrier, whose height can, in the ideal case, be predicted by the Schottky-Mott rule2-4 on the basis of the relative alignment of energy levels. Such ideal physics has rarely been experimentally realized, however, because of the inevitable chemical disorder and Fermi-level pinning at typical metal-semiconductor interfaces2,5-12. Here we report the creation of van der Waals metal-semiconductor junctions in which atomically flat metal thin films are laminated onto two-dimensional semiconductors without direct chemical bonding, creating an interface that is essentially free from chemical disorder and Fermi-level pinning. The Schottky barrier height, which approaches the Schottky-Mott limit, is dictated by the work function of the metal and is thus highly tunable. By transferring metal films (silver or platinum) with a work function that matches the conduction band or valence band edges of molybdenum sulfide, we achieve transistors with a two-terminal electron mobility at room temperature of 260 centimetres squared per volt per second and a hole mobility of 175 centimetres squared per volt per second. Furthermore, by using asymmetric contact pairs with different work functions, we demonstrate a silver/molybdenum sulfide/platinum photodiode with an open-circuit voltage of 1.02 volts. Our study not only experimentally validates the fundamental limit of ideal metal-semiconductor junctions but also defines a highly efficient and damage-free strategy for metal integration that could be used in high-performance electronics and optoelectronics.}, } @article {pmid29769728, year = {2018}, author = {Rodell, M and Famiglietti, JS and Wiese, DN and Reager, JT and Beaudoing, HK and Landerer, FW and Lo, MH}, title = {Emerging trends in global freshwater availability.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {651-659}, pmid = {29769728}, issn = {1476-4687}, support = {/GSFC/Goddard Space Flight Center NASA/United States ; 281945/SCMD-EarthScienceSystem/Science Earth Science System NASA/United States ; 967701/SCMD-EarthScienceSystem/Science Earth Science System NASA/United States ; }, mesh = {China ; Climate Change ; Food Supply ; Fresh Water/*analysis ; Groundwater/analysis ; Human Activities ; Humans ; Models, Theoretical ; Water Supply/*statistics & numerical data ; }, abstract = {Freshwater availability is changing worldwide. Here we quantify 34 trends in terrestrial water storage observed by the Gravity Recovery and Climate Experiment (GRACE) satellites during 2002-2016 and categorize their drivers as natural interannual variability, unsustainable groundwater consumption, climate change or combinations thereof. Several of these trends had been lacking thorough investigation and attribution, including massive changes in northwestern China and the Okavango Delta. Others are consistent with climate model predictions. This observation-based assessment of how the world's water landscape is responding to human impacts and climate variations provides a blueprint for evaluating and predicting emerging threats to water and food security.}, } @article {pmid29769727, year = {2018}, author = {Meisel, M and Hinterleitner, R and Pacis, A and Chen, L and Earley, ZM and Mayassi, T and Pierre, JF and Ernest, JD and Galipeau, HJ and Thuille, N and Bouziat, R and Buscarlet, M and Ringus, DL and Wang, Y and Li, Y and Dinh, V and Kim, SM and McDonald, BD and Zurenski, MA and Musch, MW and Furtado, GC and Lira, SA and Baier, G and Chang, EB and Eren, AM and Weber, CR and Busque, L and Godley, LA and Verdú, EF and Barreiro, LB and Jabri, B}, title = {Microbial signals drive pre-leukaemic myeloproliferation in a Tet2-deficient host.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {580-584}, pmid = {29769727}, issn = {1476-4687}, support = {P30 CA014599/CA/NCI NIH HHS/United States ; P30 DK042086/DK/NIDDK NIH HHS/United States ; R01 DK067180/DK/NIDDK NIH HHS/United States ; P01 DK072201/DK/NIDDK NIH HHS/United States ; R01 DK110352/DK/NIDDK NIH HHS/United States ; R01 CA161373/CA/NCI NIH HHS/United States ; F32 DK105728-01A1/NH/NIH HHS/United States ; }, mesh = {Animals ; *Asymptomatic Diseases ; Bacterial Infections/immunology/microbiology ; *Bacterial Physiological Phenomena/immunology ; *Cell Proliferation ; DNA-Binding Proteins/*deficiency/genetics ; Female ; Germ-Free Life ; Inflammation/microbiology ; Interleukin-6/immunology ; Intestinal Mucosa/metabolism ; Lactobacillus/chemistry/cytology/immunology ; Leukemia/*microbiology/*pathology ; Male ; Mice ; Penetrance ; Permeability ; Proto-Oncogene Proteins/*deficiency/genetics ; Toll-Like Receptor 2/agonists ; }, abstract = {Somatic mutations in tet methylcytosine dioxygenase 2 (TET2), which encodes an epigenetic modifier enzyme, drive the development of haematopoietic malignancies1-7. In both humans and mice, TET2 deficiency leads to increased self-renewal of haematopoietic stem cells with a net developmental bias towards the myeloid lineage1,4,8,9. However, pre-leukaemic myeloproliferation (PMP) occurs in only a fraction of Tet2-/- mice8,9 and humans with TET2 mutations1,3,5-7, suggesting that extrinsic non-cell-autonomous factors are required for disease onset. Here we show that bacterial translocation and increased interleukin-6 production, resulting from dysfunction of the small-intestinal barrier, are critical for the development of PMP in mice that lack Tet2 expression in haematopoietic cells. Furthermore, in symptom-free Tet2-/- mice, PMP can be induced by disrupting intestinal barrier integrity, or in response to systemic bacterial stimuli such as the toll-like receptor 2 agonist. PMP was reversed by antibiotic treatment and failed to develop in germ-free Tet2-/- mice, which illustrates the importance of microbial signals in the development of this condition. Our findings demonstrate the requirement for microbial-dependent inflammation in the development of PMP and provide a mechanistic basis for the variation in PMP penetrance observed in Tet2-/- mice. This study will prompt new lines of investigation that may profoundly affect the prevention and management of haematopoietic malignancies.}, } @article {pmid29769726, year = {2018}, author = {Rothhammer, V and Borucki, DM and Tjon, EC and Takenaka, MC and Chao, CC and Ardura-Fabregat, A and de Lima, KA and Gutiérrez-Vázquez, C and Hewson, P and Staszewski, O and Blain, M and Healy, L and Neziraj, T and Borio, M and Wheeler, M and Dragin, LL and Laplaud, DA and Antel, J and Alvarez, JI and Prinz, M and Quintana, FJ}, title = {Microglial control of astrocytes in response to microbial metabolites.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {724-728}, doi = {10.1038/s41586-018-0119-x}, pmid = {29769726}, issn = {1476-4687}, support = {R01 NS102807/NS/NINDS NIH HHS/United States ; R01 ES025530/ES/NIEHS NIH HHS/United States ; R01 AI126880/AI/NIAID NIH HHS/United States ; AI093903/NH/NIH HHS/United States ; NS087867/NH/NIH HHS/United States ; AI126880/NH/NIH HHS/United States ; ES02530/NH/NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/*metabolism/pathology ; Cells, Cultured ; Central Nervous System/metabolism/microbiology/pathology ; Disease Models, Animal ; Encephalomyelitis, Autoimmune, Experimental/*metabolism/*microbiology/pathology/prevention & control ; ErbB Receptors/metabolism ; Female ; Humans ; Inflammation/metabolism/microbiology/pathology/prevention & control ; Lipopolysaccharide Receptors/metabolism ; Mice ; Mice, Inbred C57BL ; Microglia/*metabolism/pathology ; Multiple Sclerosis/metabolism/pathology ; Receptors, Aryl Hydrocarbon/metabolism ; Symbiosis ; Transforming Growth Factor alpha/biosynthesis/metabolism ; Tryptophan/deficiency/metabolism ; Vascular Endothelial Growth Factor B/biosynthesis/metabolism ; Vascular Endothelial Growth Factor Receptor-1/metabolism ; }, abstract = {Microglia and astrocytes modulate inflammation and neurodegeneration in the central nervous system (CNS)1-3. Microglia modulate pro-inflammatory and neurotoxic activities in astrocytes, but the mechanisms involved are not completely understood4,5. Here we report that TGFα and VEGF-B produced by microglia regulate the pathogenic activities of astrocytes in the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Microglia-derived TGFα acts via the ErbB1 receptor in astrocytes to limit their pathogenic activities and EAE development. Conversely, microglial VEGF-B triggers FLT-1 signalling in astrocytes and worsens EAE. VEGF-B and TGFα also participate in the microglial control of human astrocytes. Furthermore, expression of TGFα and VEGF-B in CD14+ cells correlates with the multiple sclerosis lesion stage. Finally, metabolites of dietary tryptophan produced by the commensal flora control microglial activation and TGFα and VEGF-B production, modulating the transcriptional program of astrocytes and CNS inflammation through a mechanism mediated by the aryl hydrocarbon receptor. In summary, we identified positive and negative regulators that mediate the microglial control of astrocytes. Moreover, these findings define a pathway through which microbial metabolites limit pathogenic activities of microglia and astrocytes, and suppress CNS inflammation. This pathway may guide new therapies for multiple sclerosis and other neurological disorders.}, } @article {pmid29769725, year = {2018}, author = {Zhang, R and Kim, AS and Fox, JM and Nair, S and Basore, K and Klimstra, WB and Rimkunas, R and Fong, RH and Lin, H and Poddar, S and Crowe, JE and Doranz, BJ and Fremont, DH and Diamond, MS}, title = {Mxra8 is a receptor for multiple arthritogenic alphaviruses.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {570-574}, pmid = {29769725}, issn = {1476-4687}, support = {HHSN272201400058C/AI/NIAID NIH HHS/United States ; R01 AI095436/AI/NIAID NIH HHS/United States ; R01 AI114816/AI/NIAID NIH HHS/United States ; R01 AI123348/AI/NIAID NIH HHS/United States ; }, mesh = {3T3 Cells ; Animals ; Antibodies, Blocking/immunology ; CRISPR-Cas Systems/genetics ; Chikungunya virus/*metabolism/pathogenicity ; Chondrocytes/metabolism ; Fibroblasts/metabolism ; Humans ; Immunoglobulins/immunology/*metabolism ; Male ; Membrane Proteins/antagonists & inhibitors/immunology/*metabolism ; Mice ; Muscle, Skeletal/cytology/metabolism ; O'nyong-nyong Virus/*metabolism/pathogenicity ; Osteoblasts/metabolism ; Receptors, Fc/metabolism ; Receptors, Virus/deficiency/genetics/*metabolism ; }, abstract = {Arthritogenic alphaviruses comprise a group of enveloped RNA viruses that are transmitted to humans by mosquitoes and cause debilitating acute and chronic musculoskeletal disease 1 . The host factors required for alphavirus entry remain poorly characterized 2 . Here we use a genome-wide CRISPR-Cas9-based screen to identify the cell adhesion molecule Mxra8 as an entry mediator for multiple emerging arthritogenic alphaviruses, including chikungunya, Ross River, Mayaro and O'nyong nyong viruses. Gene editing of mouse Mxra8 or human MXRA8 resulted in reduced levels of viral infection of cells and, reciprocally, ectopic expression of these genes resulted in increased infection. Mxra8 bound directly to chikungunya virus particles and enhanced virus attachment and internalization into cells. Consistent with these findings, Mxra8-Fc fusion protein or anti-Mxra8 monoclonal antibodies blocked chikungunya virus infection in multiple cell types, including primary human synovial fibroblasts, osteoblasts, chondrocytes and skeletal muscle cells. Mutagenesis experiments suggest that Mxra8 binds to a surface-exposed region across the A and B domains of chikungunya virus E2 protein, which are a speculated site of attachment. Finally, administration of the Mxra8-Fc protein or anti-Mxra8 blocking antibodies to mice reduced chikungunya and O'nyong nyong virus infection as well as associated foot swelling. Pharmacological targeting of Mxra8 could form a strategy for mitigating infection and disease by multiple arthritogenic alphaviruses.}, } @article {pmid29769724, year = {2018}, author = {Jiang, D and Gamal El-Din, TM and Ing, C and Lu, P and Pomès, R and Zheng, N and Catterall, WA}, title = {Structural basis for gating pore current in periodic paralysis.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {590-594}, doi = {10.1038/s41586-018-0120-4}, pmid = {29769724}, issn = {1476-4687}, support = {R01 NS015751/NS/NINDS NIH HHS/United States ; R01 HL112808/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Binding Sites ; Electric Conductivity ; Guanidine/metabolism ; Humans ; Hypokalemic Periodic Paralysis/genetics/metabolism ; *Ion Channel Gating/genetics ; Molecular Dynamics Simulation ; Mutation ; NAV1.4 Voltage-Gated Sodium Channel/*chemistry/genetics/*metabolism ; Paralyses, Familial Periodic/genetics/*metabolism ; Sodium/metabolism ; Thermodynamics ; }, abstract = {Potassium-sensitive hypokalaemic and normokalaemic periodic paralysis are inherited skeletal muscle diseases characterized by episodes of flaccid muscle weakness1,2. They are caused by single mutations in positively charged residues ('gating charges') in the S4 transmembrane segment of the voltage sensor of the voltage-gated sodium channel Nav1.4 or the calcium channel Cav1.11,2. Mutations of the outermost gating charges (R1 and R2) cause hypokalaemic periodic paralysis1,2 by creating a pathogenic gating pore in the voltage sensor through which cations leak in the resting state3,4. Mutations of the third gating charge (R3) cause normokalaemic periodic paralysis 5 owing to cation leak in both activated and inactivated states 6 . Here we present high-resolution structures of the model bacterial sodium channel NavAb with the analogous gating-charge mutations7,8, which have similar functional effects as in the human channels. The R2G and R3G mutations have no effect on the backbone structures of the voltage sensor, but they create an aqueous cavity near the hydrophobic constriction site that controls gating charge movement through the voltage sensor. The R3G mutation extends the extracellular aqueous cleft through the entire length of the activated voltage sensor, creating an aqueous path through the membrane. Conversely, molecular modelling shows that the R2G mutation creates a continuous aqueous path through the membrane only in the resting state. Crystal structures of NavAb(R2G) in complex with guanidinium define a potential drug target site. Molecular dynamics simulations illustrate the mechanism of Na+ permeation through the mutant gating pore in concert with conformational fluctuations of the gating charge R4. Our results reveal pathogenic mechanisms of periodic paralysis at the atomic level and suggest designs of drugs that may prevent ionic leak and provide symptomatic relief from hypokalaemic and normokalaemic periodic paralysis.}, } @article {pmid29769723, year = {2018}, author = {Deneka, D and Sawicka, M and Lam, AKM and Paulino, C and Dutzler, R}, title = {Structure of a volume-regulated anion channel of the LRRC8 family.}, journal = {Nature}, volume = {558}, number = {7709}, pages = {254-259}, doi = {10.1038/s41586-018-0134-y}, pmid = {29769723}, issn = {1476-4687}, mesh = {Animals ; Cell Membrane/metabolism ; Connexins/chemistry ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; Cytoplasm/metabolism ; HEK293 Cells ; Humans ; *Ion Channel Gating ; Membrane Proteins/*chemistry/metabolism/*ultrastructure ; Mice ; Models, Molecular ; Protein Domains ; Protein Subunits/chemistry/metabolism ; Proteins/*chemistry/metabolism/*ultrastructure ; Static Electricity ; Structure-Activity Relationship ; }, abstract = {Volume-regulated anion channels are activated in response to hypotonic stress. These channels are composed of closely related paralogues of the leucine-rich repeat-containing protein 8 (LRRC8) family that co-assemble to form hexameric complexes. Here, using cryo-electron microscopy and X-ray crystallography, we determine the structure of a homomeric channel of the obligatory subunit LRRC8A. This protein conducts ions and has properties in common with endogenous heteromeric channels. Its modular structure consists of a transmembrane pore domain followed by a cytoplasmic leucine-rich repeat domain. The transmembrane domain, which is structurally related to connexin proteins, is wide towards the cytoplasm but constricted on the outside by a structural unit that acts as a selectivity filter. An excess of basic residues in the filter and throughout the pore attracts anions by electrostatic interaction. Our work reveals the previously unknown architecture of volume-regulated anion channels and their mechanism of selective anion conduction.}, } @article {pmid29769722, year = {2018}, author = {Simoni, Y and Becht, E and Fehlings, M and Loh, CY and Koo, SL and Teng, KWW and Yeong, JPS and Nahar, R and Zhang, T and Kared, H and Duan, K and Ang, N and Poidinger, M and Lee, YY and Larbi, A and Khng, AJ and Tan, E and Fu, C and Mathew, R and Teo, M and Lim, WT and Toh, CK and Ong, BH and Koh, T and Hillmer, AM and Takano, A and Lim, TKH and Tan, EH and Zhai, W and Tan, DSW and Tan, IB and Newell, EW}, title = {Bystander CD8+ T cells are abundant and phenotypically distinct in human tumour infiltrates.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {575-579}, doi = {10.1038/s41586-018-0130-2}, pmid = {29769722}, issn = {1476-4687}, mesh = {Antigens, Neoplasm/immunology ; Antigens, Viral/immunology ; Apyrase/analysis/deficiency/metabolism ; Bystander Effect/*immunology ; CD8-Positive T-Lymphocytes/*cytology/*immunology/metabolism ; Cell Separation ; Colorectal Neoplasms/genetics/*immunology ; ErbB Receptors/genetics ; Humans ; Lung Neoplasms/genetics/*immunology ; Lymphocytes, Tumor-Infiltrating/*cytology/*immunology/metabolism ; Phenotype ; }, abstract = {Various forms of immunotherapy, such as checkpoint blockade immunotherapy, are proving to be effective at restoring T cell-mediated immune responses that can lead to marked and sustained clinical responses, but only in some patients and cancer types1-4. Patients and tumours may respond unpredictably to immunotherapy partly owing to heterogeneity of the immune composition and phenotypic profiles of tumour-infiltrating lymphocytes (TILs) within individual tumours and between patients5,6. Although there is evidence that tumour-mutation-derived neoantigen-specific T cells play a role in tumour control2,4,7-10, in most cases the antigen specificities of phenotypically diverse tumour-infiltrating T cells are largely unknown. Here we show that human lung and colorectal cancer CD8+ TILs can not only be specific for tumour antigens (for example, neoantigens), but also recognize a wide range of epitopes unrelated to cancer (such as those from Epstein-Barr virus, human cytomegalovirus or influenza virus). We found that these bystander CD8+ TILs have diverse phenotypes that overlap with tumour-specific cells, but lack CD39 expression. In colorectal and lung tumours, the absence of CD39 in CD8+ TILs defines populations that lack hallmarks of chronic antigen stimulation at the tumour site, supporting their classification as bystanders. Expression of CD39 varied markedly between patients, with some patients having predominantly CD39- CD8+ TILs. Furthermore, frequencies of CD39 expression among CD8+ TILs correlated with several important clinical parameters, such as the mutation status of lung tumour epidermal growth factor receptors. Our results demonstrate that not all tumour-infiltrating T cells are specific for tumour antigens, and suggest that measuring CD39 expression could be a straightforward way to quantify or isolate bystander T cells.}, } @article {pmid29769721, year = {2018}, author = {Wan, G and Fields, BD and Spracklin, G and Shukla, A and Phillips, CM and Kennedy, S}, title = {Spatiotemporal regulation of liquid-like condensates in epigenetic inheritance.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {679-683}, doi = {10.1038/s41586-018-0132-0}, pmid = {29769721}, issn = {1476-4687}, support = {R01 GM088289/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Argonaute Proteins/genetics/*metabolism ; Caenorhabditis elegans/cytology/enzymology/*genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Conserved Sequence ; DNA-Binding Proteins/metabolism ; Epigenesis, Genetic/*genetics ; Germ Cells/metabolism ; Organelles/*chemistry/*metabolism ; RNA Helicases/genetics/*metabolism ; *RNA Interference ; }, abstract = {Non-membrane-bound organelles such as nucleoli, processing bodies, Cajal bodies and germ granules form by the spontaneous self-assembly of specific proteins and RNAs. How these biomolecular condensates form and interact is poorly understood. Here we identify two proteins, ZNFX-1 and WAGO-4, that localize to Caenorhabditis elegans germ granules (P granules) in early germline blastomeres. Later in germline development, ZNFX-1 and WAGO-4 separate from P granules to define an independent liquid-like condensate that we term the Z granule. In adult germ cells, Z granules assemble into ordered tri-condensate assemblages with P granules and Mutator foci, which we term PZM granules. Finally, we show that one biological function of ZNFX-1 and WAGO-4 is to interact with silencing RNAs in the C. elegans germline to direct transgenerational epigenetic inheritance. We speculate that the temporal and spatial ordering of liquid droplet organelles may help cells to organize and coordinate the complex RNA processing pathways that underlie gene-regulatory systems, such as RNA-directed transgenerational epigenetic inheritance.}, } @article {pmid29769720, year = {2018}, author = {Szenker-Ravi, E and Altunoglu, U and Leushacke, M and Bosso-Lefèvre, C and Khatoo, M and Thi Tran, H and Naert, T and Noelanders, R and Hajamohideen, A and Beneteau, C and de Sousa, SB and Karaman, B and Latypova, X and Başaran, S and Yücel, EB and Tan, TT and Vlaminck, L and Nayak, SS and Shukla, A and Girisha, KM and Le Caignec, C and Soshnikova, N and Uyguner, ZO and Vleminckx, K and Barker, N and Kayserili, H and Reversade, B}, title = {RSPO2 inhibition of RNF43 and ZNRF3 governs limb development independently of LGR4/5/6.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {564-569}, doi = {10.1038/s41586-018-0118-y}, pmid = {29769720}, issn = {1476-4687}, mesh = {Animals ; DNA-Binding Proteins/*antagonists & inhibitors/metabolism ; Extremities/*embryology ; Female ; Fibroblasts ; Gene Knockout Techniques ; HEK293 Cells ; Humans ; Intercellular Signaling Peptides and Proteins/genetics/*metabolism ; Limb Deformities, Congenital/*genetics ; Male ; Mice ; Oncogene Proteins/antagonists & inhibitors/metabolism ; Phenotype ; Receptors, G-Protein-Coupled/deficiency/*metabolism ; Ubiquitin-Protein Ligases/*antagonists & inhibitors/metabolism ; Xenopus/genetics ; }, abstract = {The four R-spondin secreted ligands (RSPO1-RSPO4) act via their cognate LGR4, LGR5 and LGR6 receptors to amplify WNT signalling1-3. Here we report an allelic series of recessive RSPO2 mutations in humans that cause tetra-amelia syndrome, which is characterized by lung aplasia and a total absence of the four limbs. Functional studies revealed impaired binding to the LGR4/5/6 receptors and the RNF43 and ZNRF3 transmembrane ligases, and reduced WNT potentiation, which correlated with allele severity. Unexpectedly, however, the triple and ubiquitous knockout of Lgr4, Lgr5 and Lgr6 in mice did not recapitulate the known Rspo2 or Rspo3 loss-of-function phenotypes. Moreover, endogenous depletion or addition of exogenous RSPO2 or RSPO3 in triple-knockout Lgr4/5/6 cells could still affect WNT responsiveness. Instead, we found that the concurrent deletion of rnf43 and znrf3 in Xenopus embryos was sufficient to trigger the outgrowth of supernumerary limbs. Our results establish that RSPO2, without the LGR4/5/6 receptors, serves as a direct antagonistic ligand to RNF43 and ZNRF3, which together constitute a master switch that governs limb specification. These findings have direct implications for regenerative medicine and WNT-associated cancers.}, } @article {pmid29769719, year = {2018}, author = {Chen, J and Ou, Y and Yang, Y and Li, W and Xu, Y and Xie, Y and Liu, Y}, title = {KLHL22 activates amino-acid-dependent mTORC1 signalling to promote tumorigenesis and ageing.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {585-589}, doi = {10.1038/s41586-018-0128-9}, pmid = {29769719}, issn = {1476-4687}, mesh = {Adaptor Proteins, Signal Transducing/deficiency/*metabolism ; Aging/genetics/*metabolism ; Animals ; Autophagy ; Breast Neoplasms/metabolism ; Caenorhabditis elegans/genetics/metabolism ; Caenorhabditis elegans Proteins/metabolism ; Carcinogenesis/genetics/*metabolism ; Cell Line ; Cell Proliferation ; Cullin Proteins/metabolism ; Female ; GTPase-Activating Proteins/metabolism ; Humans ; Longevity/genetics ; Mechanistic Target of Rapamycin Complex 1/*metabolism ; Mice ; Mice, Nude ; Multiprotein Complexes/metabolism ; Oncogenes ; Proteolysis ; Repressor Proteins/metabolism ; *Signal Transduction ; Tumor Suppressor Proteins/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; }, abstract = {The mechanistic target of rapamycin complex 1 (mTORC1) is a master regulator of cell growth that responds to a diverse set of environmental cues, including amino acids1,2. Deregulation of mTORC1 has been linked with metabolic diseases, cancer and ageing2-4. In response to amino acids, mTORC1 is recruited by the Rag GTPases to the lysosome, its site of activation5,6. The GATOR1 complex, consisting of DEPDC5, NPRL3 and NPRL2, displays GAP activity to inactivate Rag GTPases under amino-acid-deficient conditions 7 . However, it is unclear how the inhibitory function of GATOR1 is released upon amino acid stimulation. Here we find that in response to amino acids, the CUL3-KLHL22 E3 ubiquitin ligase promotes K48-linked polyubiquitination and degradation of DEPDC5, an essential subunit of GATOR1. KLHL22 plays a conserved role to mediate the activation of mTORC1 and downstream events in mammals and nematodes. Depletion of MEL-26, the Caenorhabditis elegans orthologue of KLHL22, extends worm lifespan. Moreover, KLHL22 levels are elevated in tumours of breast cancer patients, whereas DEPDC5 levels are correspondingly reduced. Depletion of KLHL22 in breast cancer cells suppresses tumour growth in nude mice. Therefore, pharmacological interventions targeting KLHL22 may have therapeutic potential for the treatment of breast cancer and age-related diseases.}, } @article {pmid29769718, year = {2018}, author = {Vo, MN and Terrey, M and Lee, JW and Roy, B and Moresco, JJ and Sun, L and Fu, H and Liu, Q and Weber, TG and Yates, JR and Fredrick, K and Schimmel, P and Ackerman, SL}, title = {ANKRD16 prevents neuron loss caused by an editing-defective tRNA synthetase.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {510-515}, pmid = {29769718}, issn = {1476-4687}, support = {R01 CA092577/CA/NCI NIH HHS/United States ; R01 GM072528/GM/NIGMS NIH HHS/United States ; R01 NS042613/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Alanine/metabolism ; Alanine-tRNA Ligase/chemistry/*genetics/*metabolism ; Animals ; Catalytic Domain ; Cell Death ; Female ; Lysine/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; *Mutation ; Protein Binding ; *Protein Biosynthesis ; Purkinje Cells/*enzymology/metabolism/*pathology ; Serine/metabolism ; }, abstract = {Editing domains of aminoacyl tRNA synthetases correct tRNA charging errors to maintain translational fidelity. A mutation in the editing domain of alanyl tRNA synthetase (AlaRS) in Aars sti mutant mice results in an increase in the production of serine-mischarged tRNAAla and the degeneration of cerebellar Purkinje cells. Here, using positional cloning, we identified Ankrd16, a gene that acts epistatically with the Aars sti mutation to attenuate neurodegeneration. ANKRD16, a vertebrate-specific protein that contains ankyrin repeats, binds directly to the catalytic domain of AlaRS. Serine that is misactivated by AlaRS is captured by the lysine side chains of ANKRD16, which prevents the charging of serine adenylates to tRNAAla and precludes serine misincorporation in nascent peptides. The deletion of Ankrd16 in the brains of Aarssti/sti mice causes widespread protein aggregation and neuron loss. These results identify an amino-acid-accepting co-regulator of tRNA synthetase editing as a new layer of the machinery that is essential to the prevention of severe pathologies that arise from defects in editing.}, } @article {pmid29769717, year = {2018}, author = {Wang, Z and Ma, Z and Castillo-González, C and Sun, D and Li, Y and Yu, B and Zhao, B and Li, P and Zhang, X}, title = {SWI2/SNF2 ATPase CHR2 remodels pri-miRNAs via Serrate to impede miRNA production.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {516-521}, doi = {10.1038/s41586-018-0135-x}, pmid = {29769717}, issn = {1476-4687}, mesh = {Adenosine Triphosphatases/*metabolism ; Arabidopsis/*enzymology/genetics ; Arabidopsis Proteins/*metabolism ; Gene Expression Regulation, Plant ; MicroRNAs/*biosynthesis/genetics/metabolism ; Protein Binding ; RNA Folding ; RNA Processing, Post-Transcriptional ; RNA-Binding Proteins/*metabolism ; Transcription, Genetic ; }, abstract = {Chromatin remodelling factors (CHRs) typically function to alter chromatin structure. CHRs also reside in ribonucleoprotein complexes, but little is known about their RNA-related functions. Here we show that CHR2 (also known as BRM), the ATPase subunit of the large switch/sucrose non-fermentable (SWI/SNF) complex, is a partner of the Microprocessor component Serrate (SE). CHR2 promotes the transcription of primary microRNA precursors (pri-miRNAs) while repressing miRNA accumulation in vivo. Direct interaction with SE is required for post-transcriptional inhibition of miRNA accumulation by CHR2 but not for its transcriptional activity. CHR2 can directly bind to and unwind pri-miRNAs and inhibit their processing, and this inhibition requires the remodelling and helicase activity of CHR2 in vitro and in vivo. Furthermore, the secondary structures of pri-miRNAs differed between wild-type Arabidopsis thaliana and chr2 mutants. We conclude that CHR2 accesses pri-miRNAs through SE and remodels their secondary structures, preventing downstream processing by DCL1 and HYL1. Our study uncovers pri-miRNAs as a substrate of CHR2, and an additional regulatory layer upstream of Microprocessor activity to control miRNA accumulation.}, } @article {pmid29769716, year = {2018}, author = {Price, MN and Wetmore, KM and Waters, RJ and Callaghan, M and Ray, J and Liu, H and Kuehl, JV and Melnyk, RA and Lamson, JS and Suh, Y and Carlson, HK and Esquivel, Z and Sadeeshkumar, H and Chakraborty, R and Zane, GM and Rubin, BE and Wall, JD and Visel, A and Bristow, J and Blow, MJ and Arkin, AP and Deutschbauer, AM}, title = {Mutant phenotypes for thousands of bacterial genes of unknown function.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {503-509}, doi = {10.1038/s41586-018-0124-0}, pmid = {29769716}, issn = {1476-4687}, support = {S10 RR029668/RR/NCRR NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; }, mesh = {Bacteria/cytology/*genetics ; Bacterial Proteins/classification/genetics/physiology ; Conserved Sequence ; DNA Repair/genetics ; Genes, Bacterial/*genetics ; Genetic Fitness ; Genome, Bacterial/genetics ; *Molecular Sequence Annotation ; Mutant Proteins/classification/genetics/physiology ; *Mutation ; *Phenotype ; *Uncertainty ; }, abstract = {One-third of all protein-coding genes from bacterial genomes cannot be annotated with a function. Here, to investigate the functions of these genes, we present genome-wide mutant fitness data from 32 diverse bacteria across dozens of growth conditions. We identified mutant phenotypes for 11,779 protein-coding genes that had not been annotated with a specific function. Many genes could be associated with a specific condition because the gene affected fitness only in that condition, or with another gene in the same bacterium because they had similar mutant phenotypes. Of the poorly annotated genes, 2,316 had associations that have high confidence because they are conserved in other bacteria. By combining these conserved associations with comparative genomics, we identified putative DNA repair proteins; in addition, we propose specific functions for poorly annotated enzymes and transporters and for uncharacterized protein families. Our study demonstrates the scalability of microbial genetics and its utility for improving gene annotations.}, } @article {pmid29769715, year = {2018}, author = {Campbell, ET and Terhal, BM and Vuillot, C}, title = {Author Correction: Roads towards fault-tolerant universal quantum computation.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {E6}, doi = {10.1038/s41586-018-0116-0}, pmid = {29769715}, issn = {1476-4687}, abstract = {In Fig. 2b of this Review, two of the gates were inadvertently swapped. At the top right, 'Xa+c' should have been 'Zb', and at the bottom right 'Zb' should have been 'Xa+c'. Fig. 2b has been corrected online. The Supplementary Information of this Author Correction contains the original, incorrect Fig. 2b, for transparency.}, } @article {pmid29769714, year = {2018}, author = {Bahr, C and von Paleske, L and Uslu, VV and Remeseiro, S and Takayama, N and Ng, SW and Murison, A and Langenfeld, K and Petretich, M and Scognamiglio, R and Zeisberger, P and Benk, AS and Amit, I and Zandstra, PW and Lupien, M and Dick, JE and Trumpp, A and Spitz, F}, title = {Author Correction: A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies.}, journal = {Nature}, volume = {558}, number = {7711}, pages = {E4}, doi = {10.1038/s41586-018-0113-3}, pmid = {29769714}, issn = {1476-4687}, abstract = {In the originally published version of this Letter, ref. 43 was erroneously provided twice. In the 'Estimation of relative cell-type-specific composition of AML samples' section in the Methods, the citation to ref. 43 after the GEO dataset GSE24759 is correct. However, in the 'Mice' section of the Methods, the citation to ref. 43 after 'TAMERE' should have been associated with a new reference1. The original Letter has been corrected online (with the new reference included as ref. 49).}, } @article {pmid29769713, year = {2018}, author = {Lasko, LM and Jakob, CG and Edalji, RP and Qiu, W and Montgomery, D and Digiammarino, EL and Hansen, TM and Risi, RM and Frey, R and Manaves, V and Shaw, B and Algire, M and Hessler, P and Lam, LT and Uziel, T and Faivre, E and Ferguson, D and Buchanan, FG and Martin, RL and Torrent, M and Chiang, GG and Karukurichi, K and Langston, JW and Weinert, BT and Choudhary, C and de Vries, P and Kluge, AF and Patane, MA and Van Drie, JH and Wang, C and McElligott, D and Kesicki, EA and Marmorstein, R and Sun, C and Cole, PA and Rosenberg, SH and Michaelides, MR and Lai, A and Bromberg, KD}, title = {Author Correction: Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {E1}, doi = {10.1038/s41586-018-0111-5}, pmid = {29769713}, issn = {1476-4687}, abstract = {In the originally published version of this Letter, the authors Arthur F. Kluge, Michael A. Patane and Ce Wang were inadvertently omitted from the author list. Their affiliations are: I-to-D, Inc., PO Box 6177, Lincoln, Massachusetts 01773, USA (A.F.K.); Mitobridge, Inc. 1030 Massachusetts Avenue, Cambridge, Massachusetts 02139, USA (M.A.P.); and China Novartis Institutes for BioMedical Research, No. 4218 Jinke Road, Zhangjiang Hi-Tech Park, Pudong District, Shanghai 201203, China (C.W.). These authors contributed to the interpretation of results and design of compounds. In addition, author 'Edward A. Kesicki' was misspelled as 'Ed Kesicki'. These errors have been corrected online.}, } @article {pmid29769712, year = {2018}, author = {Peng, M and Yin, N and Li, MO}, title = {Author Correction: SZT2 dictates GATOR control of mTORC1 signalling.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {E2}, doi = {10.1038/s41586-018-0114-2}, pmid = {29769712}, issn = {1476-4687}, abstract = {In the originally published version of this Letter, there was an error in Extended Data Fig. 7e and the corresponding uncropped blots in the Supplementary Information. The actin bands in the last blot of Extended Data Fig. 7e were duplicates of the corresponding actin bands in the last blot of Extended Data Fig. 7 f. (In the uncropped blot for Extended Data Fig. 7e, the actin bands were mislabelled as 'WDR59' and this led to the error.) Extended Data Fig. 7 and the Supplementary Information of the original Letter have been corrected online. (The Supplementary Information to this Amendment contains the original Extended Data Fig. 7, and the original incorrect Supplementary Information.) We apologise for this error, which does not affect the conclusions of the paper.}, } @article {pmid29769711, year = {2018}, author = {Kurnosov, A and Marquardt, H and Frost, DJ and Ballaran, TB and Ziberna, L}, title = {Author Correction: Evidence for a Fe3+-rich pyrolitic lower mantle from (Al,Fe)-bearing bridgmanite elasticity data.}, journal = {Nature}, volume = {558}, number = {7710}, pages = {E3}, doi = {10.1038/s41586-018-0115-1}, pmid = {29769711}, issn = {1476-4687}, abstract = {In Extended Data Table 1 of this Letter, some of the elastic constants were reported incorrectly. This occurred as a result of an error in the script used to generate the numbers. The values of the elastic constants at room pressure cited in the manuscript on page 544 were derived using the same erroneous script, and the correct values and 1σ-uncertainties in the last given digit are C11 = 461.3(17) GPa instead of 462.7(17) GPa; C22 = 509.7(26) GPa instead of 504.9(26) GPa; C33 = 425.7(5) GPa instead of 426.6(5) GPa; C44 = 188.8(6) GPa instead of 188.4(6) GPa; C55 = 166.5(4) GPa instead of 166.6(4) GPa; C66 = 127.2(17) GPa instead of 129.7(17) GPa; C12 = 141.7(14) GPa instead of 140.2(14) GPa; C13 = 130.0(11) GPa instead of 132.2(11) GPa; and C23 = 161.0(12) GPa instead of 159.3(12) GPa. These errors do not affect any of the conclusions and we apologize for any confusion this may have caused. Extended Data Table 1 and the room-pressure values in the text have been corrected online. The Supplementary Information of this Author Correction contains the original, incorrect Extended Data Table 1, for transparency.}, } @article {pmid29769692, year = {2018}, author = {}, title = {Lava flows, stem-cell crackdown and Ebola returns.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {284-285}, doi = {10.1038/d41586-018-05141-w}, pmid = {29769692}, issn = {1476-4687}, } @article {pmid29769691, year = {2018}, author = {Schiermeier, Q}, title = {Europe is demolishing its dams to restore ecosystems.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {290-291}, doi = {10.1038/d41586-018-05182-1}, pmid = {29769691}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/physiology ; Conservation of Natural Resources/economics/*methods/*trends ; *Ecosystem ; *European Union/economics ; Fishes/physiology ; Introduced Species ; Power Plants/*supply & distribution ; Rivers ; Spain ; United States ; Water Supply ; }, } @article {pmid29769690, year = {2018}, author = {Gunsalus, CK and Robinson, AD}, title = {Nine pitfalls of research misconduct.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {297-299}, doi = {10.1038/d41586-018-05145-6}, pmid = {29769690}, issn = {1476-4687}, mesh = {Ethics, Research/education ; Management Audit/methods ; Research Personnel/education/*ethics/*psychology ; Scientific Misconduct/*psychology ; }, } @article {pmid29769689, year = {2018}, author = {Mendoza-Denton, R and Patt, C and Richards, M}, title = {Go beyond bias training.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {299-301}, doi = {10.1038/d41586-018-05144-7}, pmid = {29769689}, issn = {1476-4687}, mesh = {Authorship ; Chemistry ; Education, Graduate ; Efficiency ; Mentoring/*methods/standards ; Mentors/education/psychology ; Minority Groups/education/psychology/statistics & numerical data ; Prejudice/*prevention & control/psychology/*statistics & numerical data ; Racism/prevention & control/statistics & numerical data ; Research Personnel/*education/*psychology/statistics & numerical data ; Science/*education ; Sexism/prevention & control/statistics & numerical data ; Trust ; Uncertainty ; Workforce ; }, } @article {pmid29769688, year = {2018}, author = {Kwok, R}, title = {How lab heads can learn to lead.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {457-459}, doi = {10.1038/d41586-018-05156-3}, pmid = {29769688}, issn = {1476-4687}, mesh = {Commerce/economics/methods/organization & administration ; Formative Feedback ; Job Satisfaction ; Laboratories/economics/*organization & administration ; *Leadership ; Mentoring/*methods ; Mentors/*education/*psychology ; Research Personnel/*education/*psychology ; Sex Factors ; Vocational Guidance ; }, } @article {pmid29769687, year = {2018}, author = {Norris, D and Dirnagl, U and Zigmond, MJ and Thompson-Peer, K and Chow, TT}, title = {Health tips for research groups.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {302-304}, doi = {10.1038/d41586-018-05146-5}, pmid = {29769687}, issn = {1476-4687}, mesh = {Academies and Institutes/organization & administration ; Education, Graduate ; *Efficiency, Organizational ; Faculty/psychology ; *Job Satisfaction ; Laboratories/*organization & administration ; *Leadership ; Occupational Stress/prevention & control ; Research Personnel/education/*psychology/*standards ; Universities/organization & administration ; Workforce ; }, } @article {pmid29769686, year = {2018}, author = {Van Noorden, R}, title = {Some hard numbers on science's leadership problems.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {294-296}, doi = {10.1038/d41586-018-05143-8}, pmid = {29769686}, issn = {1476-4687}, mesh = {Formative Feedback ; *Job Satisfaction ; *Leadership ; Mentors/education/psychology ; *Personnel Management/methods/standards ; Research Personnel/education/*psychology ; Science/*organization & administration ; Workforce ; }, } @article {pmid29769685, year = {2018}, author = {}, title = {How to grow a healthy lab.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {293}, doi = {10.1038/d41586-018-05142-9}, pmid = {29769685}, issn = {1476-4687}, mesh = {Education, Graduate ; *Job Satisfaction ; Laboratories/*organization & administration ; *Leadership ; Mentoring/methods/standards ; Mentors/*psychology ; Research Personnel/education/*psychology ; Surveys and Questionnaires ; Workforce ; }, } @article {pmid29769684, year = {2018}, author = {Winchester, C}, title = {Give every paper a read for reproducibility.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {281}, doi = {10.1038/d41586-018-05140-x}, pmid = {29769684}, issn = {1476-4687}, mesh = {Archives ; Data Curation/methods/standards/*trends ; Mentoring/methods/standards ; Plagiarism ; *Reading ; Reproducibility of Results ; Research Design ; Research Personnel/education/*ethics/*standards ; Research Report/*standards ; Retraction of Publication as Topic ; Scientific Misconduct/statistics & numerical data ; United Kingdom ; }, } @article {pmid29769683, year = {2018}, author = {}, title = {Research institutions must put the health of labs first.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {279-280}, doi = {10.1038/d41586-018-05159-0}, pmid = {29769683}, issn = {1476-4687}, mesh = {*Laboratories ; *Research ; }, } @article {pmid29769682, year = {2018}, author = {}, title = {A slow road for stem cells.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {279}, doi = {10.1038/d41586-018-05160-7}, pmid = {29769682}, issn = {1476-4687}, mesh = {*Regeneration ; Stem Cell Transplantation ; *Stem Cells ; }, } @article {pmid29769680, year = {2018}, author = {Shirriff, K}, title = {Get facts straight on computer women.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {309}, doi = {10.1038/d41586-018-05152-7}, pmid = {29769680}, issn = {1476-4687}, mesh = {*Computers ; Female ; Humans ; *Mathematics ; }, } @article {pmid29769679, year = {2018}, author = {Olbrich, S}, title = {Treating brainwaves is not an option.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {309}, doi = {10.1038/d41586-018-05150-9}, pmid = {29769679}, issn = {1476-4687}, mesh = {*Brain Waves ; *Neurosciences ; }, } @article {pmid29769678, year = {2018}, author = {Seitz, R}, title = {Engineer solar solutions locally to save water.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {309}, doi = {10.1038/d41586-018-05151-8}, pmid = {29769678}, issn = {1476-4687}, } @article {pmid29769677, year = {2018}, author = {Geng, Y and Sarkis, J}, title = {China-US trade spat could hit the environment.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {309}, doi = {10.1038/d41586-018-05153-6}, pmid = {29769677}, issn = {1476-4687}, mesh = {Brazil ; China ; Commerce/economics/*legislation & jurisprudence ; Conservation of Natural Resources/economics/legislation & jurisprudence/*trends ; Environmental Policy/economics/legislation & jurisprudence/*trends ; Europe ; Japan ; Renewable Energy/economics/statistics & numerical data ; Republic of Korea ; United States ; }, } @article {pmid29769676, year = {2018}, author = {Floridi, L and Taddeo, M}, title = {Romans would have denied robots legal personhood.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {309}, doi = {10.1038/d41586-018-05154-5}, pmid = {29769676}, issn = {1476-4687}, mesh = {Europe ; History, Ancient ; Humans ; *Liability, Legal ; Morals ; *Personhood ; Punishment ; Robotics/*ethics/instrumentation/*legislation & jurisprudence ; Roman World/*history ; }, } @article {pmid29769675, year = {2018}, author = {Hashimoto, T and Laporte, N and Mawatari, K and Ellis, RS and Inoue, AK and Zackrisson, E and Roberts-Borsani, G and Zheng, W and Tamura, Y and Bauer, FE and Fletcher, T and Harikane, Y and Hatsukade, B and Hayatsu, NH and Matsuda, Y and Matsuo, H and Okamoto, T and Ouchi, M and Pelló, R and Rydberg, CE and Shimizu, I and Taniguchi, Y and Umehata, H and Yoshida, N}, title = {The onset of star formation 250 million years after the Big Bang.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {392-395}, doi = {10.1038/s41586-018-0117-z}, pmid = {29769675}, issn = {1476-4687}, abstract = {A fundamental quest of modern astronomy is to locate the earliest galaxies and study how they influenced the intergalactic medium a few hundred million years after the Big Bang1-3. The abundance of star-forming galaxies is known to decline4,5 from redshifts of about 6 to 10, but a key question is the extent of star formation at even earlier times, corresponding to the period when the first galaxies might have emerged. Here we report spectroscopic observations of MACS1149-JD1 6 , a gravitationally lensed galaxy observed when the Universe was less than four per cent of its present age. We detect an emission line of doubly ionized oxygen at a redshift of 9.1096 ± 0.0006, with an uncertainty of one standard deviation. This precisely determined redshift indicates that the red rest-frame optical colour arises from a dominant stellar component that formed about 250 million years after the Big Bang, corresponding to a redshift of about 15. Our results indicate that it may be possible to detect such early episodes of star formation in similar galaxies with future telescopes.}, } @article {pmid29769674, year = {2018}, author = {Yankowitz, M and Jung, J and Laksono, E and Leconte, N and Chittari, BL and Watanabe, K and Taniguchi, T and Adam, S and Graf, D and Dean, CR}, title = {Dynamic band-structure tuning of graphene moiré superlattices with pressure.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {404-408}, doi = {10.1038/s41586-018-0107-1}, pmid = {29769674}, issn = {1476-4687}, abstract = {Heterostructures can be assembled from atomically thin materials by combining a wide range of available van der Waals crystals, providing exciting possibilities for designer electronics 1 . In many cases, beyond simply realizing new material combinations, interlayer interactions lead to emergent electronic properties that are fundamentally distinct from those of the constituent layers 2 . A critical parameter in these structures is the interlayer coupling strength, but this is often not easy to determine and is typically considered to be a fixed property of the system. Here we demonstrate that we can controllably tune the interlayer separation in van der Waals heterostructures using hydrostatic pressure, providing a dynamic way to modify their electronic properties. In devices in which graphene is encapsulated in boron nitride and aligned with one of the encapsulating layers, we observe that increasing pressure produces a superlinear increase in the moiré-superlattice-induced bandgap-nearly doubling within the studied range-together with an increase in the capacitive gate coupling to the active channel by as much as 25 per cent. Comparison to theoretical modelling highlights the role of atomic-scale structural deformations and how this can be altered with pressure. Our results demonstrate that combining hydrostatic pressure with controlled rotational order provides opportunities for dynamic band-structure engineering in van der Waals heterostructures.}, } @article {pmid29769673, year = {2018}, author = {Xia, Y and Mathis, TS and Zhao, MQ and Anasori, B and Dang, A and Zhou, Z and Cho, H and Gogotsi, Y and Yang, S}, title = {Thickness-independent capacitance of vertically aligned liquid-crystalline MXenes.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {409-412}, doi = {10.1038/s41586-018-0109-z}, pmid = {29769673}, issn = {1476-4687}, abstract = {The scalable and sustainable manufacture of thick electrode films with high energy and power densities is critical for the large-scale storage of electrochemical energy for application in transportation and stationary electric grids. Two-dimensional nanomaterials have become the predominant choice of electrode material in the pursuit of high energy and power densities owing to their large surface-area-to-volume ratios and lack of solid-state diffusion1,2. However, traditional electrode fabrication methods often lead to restacking of two-dimensional nanomaterials, which limits ion transport in thick films and results in systems in which the electrochemical performance is highly dependent on the thickness of the film1-4. Strategies for facilitating ion transport-such as increasing the interlayer spacing by intercalation5-8 or introducing film porosity by designing nanoarchitectures9,10-result in materials with low volumetric energy storage as well as complex and lengthy ion transport paths that impede performance at high charge-discharge rates. Vertical alignment of two-dimensional flakes enables directional ion transport that can lead to thickness-independent electrochemical performances in thick films11-13. However, so far only limited success11,12 has been reported, and the mitigation of performance losses remains a major challenge when working with films of two-dimensional nanomaterials with thicknesses that are near to or exceed the industrial standard of 100 micrometres. Here we demonstrate electrochemical energy storage that is independent of film thickness for vertically aligned two-dimensional titanium carbide (Ti3C2T x), a material from the MXene family (two-dimensional carbides and nitrides of transition metals (M), where X stands for carbon or nitrogen). The vertical alignment was achieved by mechanical shearing of a discotic lamellar liquid-crystal phase of Ti3C2T x . The resulting electrode films show excellent performance that is nearly independent of film thickness up to 200 micrometres, which makes them highly attractive for energy storage applications. Furthermore, the self-assembly approach presented here is scalable and can be extended to other systems that involve directional transport, such as catalysis and filtration.}, } @article {pmid29769672, year = {2018}, author = {Zhou, Q and Melton, DA}, title = {Pancreas regeneration.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {351-358}, pmid = {29769672}, issn = {1476-4687}, support = {R01 DK106253/DK/NIDDK NIH HHS/United States ; UC4 DK116280/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adult Stem Cells/cytology/transplantation ; Animals ; Cell Proliferation ; Cellular Reprogramming ; Humans ; Islets of Langerhans/cytology/growth & development/pathology/physiology ; Pancreas/cytology/growth & development/pathology/*physiology ; Pluripotent Stem Cells/cytology/transplantation ; Regeneration/*physiology ; Regenerative Medicine/*methods ; }, abstract = {The pancreas is made from two distinct components: the exocrine pancreas, a reservoir of digestive enzymes, and the endocrine islets, the source of the vital metabolic hormone insulin. Human islets possess limited regenerative ability; loss of islet β-cells in diseases such as type 1 diabetes requires therapeutic intervention. The leading strategy for restoration of β-cell mass is through the generation and transplantation of new β-cells derived from human pluripotent stem cells. Other approaches include stimulating endogenous β-cell proliferation, reprogramming non-β-cells to β-like cells, and harvesting islets from genetically engineered animals. Together these approaches form a rich pipeline of therapeutic development for pancreatic regeneration.}, } @article {pmid29769671, year = {2018}, author = {Sofroniew, MV}, title = {Dissecting spinal cord regeneration.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {343-350}, doi = {10.1038/s41586-018-0068-4}, pmid = {29769671}, issn = {1476-4687}, support = {NS084030/NH/NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/pathology ; Axons/pathology/physiology ; Chondroitin Sulfate Proteoglycans/physiology ; Gray Matter/physiology ; Humans ; Myelin Sheath/physiology ; Neural Pathways/physiology ; Neuroglia/pathology ; Spinal Cord Regeneration/*physiology ; }, abstract = {The inability to recover functions lost after severe spinal cord injury has been recognized for millennia and was first attributed to a failure of spinal cord neural regeneration over 100 years ago. The last forty years have seen intense research into achieving such regeneration, but in spite of conceptual advances and many reports announcing successful interventions, progress has been slow and often controversial. Here, I examine consequential advances and setbacks, and critically consider assumptions underlying certain approaches. I argue that expanding mechanistic knowledge about multiple forms of neural regeneration, why they fail and how they can restore function will resolve conceptual contentions and push the field forward.}, } @article {pmid29769670, year = {2018}, author = {Barker, RA and Götz, M and Parmar, M}, title = {New approaches for brain repair-from rescue to reprogramming.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {329-334}, doi = {10.1038/s41586-018-0087-1}, pmid = {29769670}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Brain/*cytology/pathology/*physiology ; Cellular Reprogramming/*physiology ; Fetal Tissue Transplantation ; Humans ; Nerve Regeneration/*physiology ; Neurodegenerative Diseases/*pathology/physiopathology/*therapy ; Regenerative Medicine/*methods ; Stem Cell Transplantation ; }, abstract = {The ability to repair or promote regeneration within the adult human brain has been envisioned for decades. Until recently, such efforts mainly involved delivery of growth factors and cell transplants designed to rescue or replace a specific population of neurons, and the results have largely been disappointing. New approaches using stem-cell-derived cell products and direct cell reprogramming have opened up the possibility of reconstructing neural circuits and achieving better repair. In this Review we briefly summarize the history of neural repair and then discuss these new therapeutic approaches, especially with respect to chronic neurodegenerative disorders.}, } @article {pmid29769669, year = {2018}, author = {Wells, JM and Watt, FM}, title = {Diverse mechanisms for endogenous regeneration and repair in mammalian organs.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {322-328}, doi = {10.1038/s41586-018-0073-7}, pmid = {29769669}, issn = {1476-4687}, support = {R01 DK092456/DK/NIDDK NIH HHS/United States ; U19 AI116491/AI/NIAID NIH HHS/United States ; P01 HD093363/HD/NICHD NIH HHS/United States ; U01 DK103117/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Aging/pathology/physiology ; Animals ; Cell Adhesion ; Cell Lineage ; Cell Transformation, Neoplastic/pathology ; Cellular Reprogramming/*physiology ; Epidermal Cells ; Epidermis/physiology ; Extracellular Matrix/physiology ; Humans ; Infection/pathology ; Inflammation/pathology ; Regeneration/*physiology ; Regenerative Medicine ; Wounds and Injuries/pathology ; }, abstract = {Mammalian organs comprise an extraordinary diversity of cell and tissue types. Regenerative organs, such as the skin and gastrointestinal tract, use resident stem cells to maintain tissue function. Organs with a lower cellular turnover, such as the liver and lungs, mostly rely on proliferation of committed progenitor cells. In many organs, injury reveals the plasticity of both resident stem cells and differentiated cells. The ability of resident cells to maintain and repair organs diminishes with age, whereas, paradoxically, the risk of cancer increases. New therapeutic approaches aim to harness cell plasticity for tissue repair and regeneration while avoiding the risk of malignant transformation of cells.}, } @article {pmid29769668, year = {2018}, author = {Burkert, VD and Elouadrhiri, L and Girod, FX}, title = {The pressure distribution inside the proton.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {396-399}, doi = {10.1038/s41586-018-0060-z}, pmid = {29769668}, issn = {1476-4687}, abstract = {The proton, one of the components of atomic nuclei, is composed of fundamental particles called quarks and gluons. Gluons are the carriers of the force that binds quarks together, and free quarks are never found in isolation-that is, they are confined within the composite particles in which they reside. The origin of quark confinement is one of the most important questions in modern particle and nuclear physics because confinement is at the core of what makes the proton a stable particle and thus provides stability to the Universe. The internal quark structure of the proton is revealed by deeply virtual Compton scattering1,2, a process in which electrons are scattered off quarks inside the protons, which subsequently emit high-energy photons, which are detected in coincidence with the scattered electrons and recoil protons. Here we report a measurement of the pressure distribution experienced by the quarks in the proton. We find a strong repulsive pressure near the centre of the proton (up to 0.6 femtometres) and a binding pressure at greater distances. The average peak pressure near the centre is about 1035 pascals, which exceeds the pressure estimated for the most densely packed known objects in the Universe, neutron stars 3 . This work opens up a new area of research on the fundamental gravitational properties of protons, neutrons and nuclei, which can provide access to their physical radii, the internal shear forces acting on the quarks and their pressure distributions.}, } @article {pmid29769667, year = {2018}, author = {Roska, B and Sahel, JA}, title = {Restoring vision.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {359-367}, doi = {10.1038/s41586-018-0076-4}, pmid = {29769667}, issn = {1476-4687}, mesh = {Animals ; Blindness/pathology/*physiopathology/*therapy ; Disease Models, Animal ; Humans ; Regeneration/*physiology ; Retina/cytology/pathology/*physiology/*physiopathology ; Translational Medical Research ; Treatment Outcome ; Vision, Ocular/*physiology ; }, abstract = {Restoring vision to the blind by retinal repair has been a dream of medicine for centuries, and the first successful procedures have recently been performed. Although we are still far from the restoration of high-resolution vision, step-by-step developments are overcoming crucial bottlenecks in therapy development and have enabled the restoration of some visual function in patients with specific blindness-causing diseases. Here, we discuss the current state of vision restoration and the problems related to retinal repair. We describe new model systems and translational technologies, as well as the clinical conditions in which new methods may help to combat blindness.}, } @article {pmid29769666, year = {2018}, author = {Montzka, SA and Dutton, GS and Yu, P and Ray, E and Portmann, RW and Daniel, JS and Kuijpers, L and Hall, BD and Mondeel, D and Siso, C and Nance, JD and Rigby, M and Manning, AJ and Hu, L and Moore, F and Miller, BR and Elkins, JW}, title = {An unexpected and persistent increase in global emissions of ozone-depleting CFC-11.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {413-417}, doi = {10.1038/s41586-018-0106-2}, pmid = {29769666}, issn = {1476-4687}, abstract = {The Montreal Protocol was designed to protect the stratospheric ozone layer by enabling reductions in the abundance of ozone-depleting substances such as chlorofluorocarbons (CFCs) in the atmosphere1-3. The reduction in the atmospheric concentration of trichlorofluoromethane (CFC-11) has made the second-largest contribution to the decline in the total atmospheric concentration of ozone-depleting chlorine since the 1990s 1 . However, CFC-11 still contributes one-quarter of all chlorine reaching the stratosphere, and a timely recovery of the stratospheric ozone layer depends on a sustained decline in CFC-11 concentrations 1 . Here we show that the rate of decline of atmospheric CFC-11 concentrations observed at remote measurement sites was constant from 2002 to 2012, and then slowed by about 50 per cent after 2012. The observed slowdown in the decline of CFC-11 concentration was concurrent with a 50 per cent increase in the mean concentration difference observed between the Northern and Southern Hemispheres, and also with the emergence of strong correlations at the Mauna Loa Observatory between concentrations of CFC-11 and other chemicals associated with anthropogenic emissions. A simple model analysis of our findings suggests an increase in CFC-11 emissions of 13 ± 5 gigagrams per year (25 ± 13 per cent) since 2012, despite reported production being close to zero 4 since 2006. Our three-dimensional model simulations confirm the increase in CFC-11 emissions, but indicate that this increase may have been as much as 50 per cent smaller as a result of changes in stratospheric processes or dynamics. The increase in emission of CFC-11 appears unrelated to past production; this suggests unreported new production, which is inconsistent with the Montreal Protocol agreement to phase out global CFC production by 2010.}, } @article {pmid29769665, year = {2018}, author = {Madl, CM and Heilshorn, SC and Blau, HM}, title = {Bioengineering strategies to accelerate stem cell therapeutics.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {335-342}, doi = {10.1038/s41586-018-0089-z}, pmid = {29769665}, issn = {1476-4687}, support = {U19 AI116484/AI/NIAID NIH HHS/United States ; R21 HL13804201/NH/NIH HHS/United States ; R01 AG020961/AG/NIA NIH HHS/United States ; R01 AR063963/AR/NIAMS NIH HHS/United States ; R01 NS089533/NS/NINDS NIH HHS/United States ; R01 HG00967401/NH/NIH HHS/United States ; }, mesh = {Animals ; Bioengineering/*methods/trends ; Cell Differentiation ; Cell Lineage ; Humans ; Regenerative Medicine/*methods/trends ; Stem Cell Transplantation/*methods/trends ; Stem Cells/*cytology ; }, abstract = {Although only a few stem cell-based therapies are currently available to patients, stem cells hold tremendous regenerative potential, and several exciting clinical applications are on the horizon. Biomaterials with tuneable mechanical and biochemical properties can preserve stem cell function in culture, enhance survival of transplanted cells and guide tissue regeneration. Rapid progress with three-dimensional hydrogel culture platforms provides the opportunity to grow patient-specific organoids, and has led to the discovery of drugs that stimulate endogenous tissue-specific stem cells and enabled screens for drugs to treat disease. Therefore, bioengineering technologies are poised to overcome current bottlenecks and revolutionize the field of regenerative medicine.}, } @article {pmid29769653, year = {2018}, author = {Perng, YC and Lenschow, DJ}, title = {ISG15 in antiviral immunity and beyond.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {423-439}, doi = {10.1038/s41579-018-0020-5}, pmid = {29769653}, issn = {1740-1534}, abstract = {The host response to viral infection includes the induction of type I interferons and the subsequent upregulation of hundreds of interferon-stimulated genes. Ubiquitin-like protein ISG15 is an interferon-induced protein that has been implicated as a central player in the host antiviral response. Over the past 15 years, efforts to understand how ISG15 protects the host during infection have revealed that its actions are diverse and pathogen-dependent. In this Review, we describe new insights into how ISG15 directly inhibits viral replication and discuss the recent finding that ISG15 modulates the host damage and repair response, immune response and other host signalling pathways. We also explore the viral immune-evasion strategies that counteract the actions of ISG15. These findings are integrated with a discussion of the recent identification of ISG15-deficient individuals and a cellular receptor for ISG15 that provides new insights into how ISG15 shapes the host response to viral infection.}, } @article {pmid29769331, year = {2018}, author = {Varala, K and Marshall-Colón, A and Cirrone, J and Brooks, MD and Pasquino, AV and Léran, S and Mittal, S and Rock, TM and Edwards, MB and Kim, GJ and Ruffel, S and McCombie, WR and Shasha, D and Coruzzi, GM}, title = {Temporal transcriptional logic of dynamic regulatory networks underlying nitrogen signaling and use in plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {6494-6499}, pmid = {29769331}, issn = {1091-6490}, support = {F32 GM095273/GM/NIGMS NIH HHS/United States ; F32 GM116347/GM/NIGMS NIH HHS/United States ; R01 GM032877/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*genetics/*metabolism ; Arabidopsis Proteins/genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant/*genetics ; Gene Regulatory Networks/*genetics ; Logic ; Nitrogen/*metabolism ; Protein Binding/genetics ; Signal Transduction/genetics ; Transcription Factors/genetics ; Transcription, Genetic/*genetics ; }, abstract = {This study exploits time, the relatively unexplored fourth dimension of gene regulatory networks (GRNs), to learn the temporal transcriptional logic underlying dynamic nitrogen (N) signaling in plants. Our "just-in-time" analysis of time-series transcriptome data uncovered a temporal cascade of cis elements underlying dynamic N signaling. To infer transcription factor (TF)-target edges in a GRN, we applied a time-based machine learning method to 2,174 dynamic N-responsive genes. We experimentally determined a network precision cutoff, using TF-regulated genome-wide targets of three TF hubs (CRF4, SNZ, and CDF1), used to "prune" the network to 155 TFs and 608 targets. This network precision was reconfirmed using genome-wide TF-target regulation data for four additional TFs (TGA1, HHO5/6, and PHL1) not used in network pruning. These higher-confidence edges in the GRN were further filtered by independent TF-target binding data, used to calculate a TF "N-specificity" index. This refined GRN identifies the temporal relationship of known/validated regulators of N signaling (NLP7/8, TGA1/4, NAC4, HRS1, and LBD37/38/39) and 146 additional regulators. Six TFs-CRF4, SNZ, CDF1, HHO5/6, and PHL1-validated herein regulate a significant number of genes in the dynamic N response, targeting 54% of N-uptake/assimilation pathway genes. Phenotypically, inducible overexpression of CRF4 in planta regulates genes resulting in altered biomass, root development, and 15NO3- uptake, specifically under low-N conditions. This dynamic N-signaling GRN now provides the temporal "transcriptional logic" for 155 candidate TFs to improve nitrogen use efficiency with potential agricultural applications. Broadly, these time-based approaches can uncover the temporal transcriptional logic for any biological response system in biology, agriculture, or medicine.}, } @article {pmid29769330, year = {2018}, author = {Osenberg, S and Karten, A and Sun, J and Li, J and Charkowick, S and Felice, CA and Kritzer, M and Nguyen, MVC and Yu, P and Ballas, N}, title = {Activity-dependent aberrations in gene expression and alternative splicing in a mouse model of Rett syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5363-E5372}, doi = {10.1073/pnas.1722546115}, pmid = {29769330}, issn = {1091-6490}, support = {R21 MH102711/MH/NIMH NIH HHS/United States ; }, mesh = {Alternative Splicing/genetics ; Animals ; Brain/metabolism ; Disease Models, Animal ; Exons/genetics ; Gene Expression/genetics ; Genes, X-Linked ; Hippocampus/metabolism ; Introns/genetics ; Methyl-CpG-Binding Protein 2/*genetics/*metabolism ; Mice ; Mice, Knockout ; Neurons/metabolism ; Rett Syndrome/*genetics/metabolism ; Transcriptome/genetics ; }, abstract = {Rett syndrome (RTT) is a severe neurodevelopmental disorder that affects about 1 in 10,000 female live births. The underlying cause of RTT is mutations in the X-linked gene, methyl-CpG-binding protein 2 (MECP2); however, the molecular mechanism by which these mutations mediate the RTT neuropathology remains enigmatic. Specifically, although MeCP2 is known to act as a transcriptional repressor, analyses of the RTT brain at steady-state conditions detected numerous differentially expressed genes, while the changes in transcript levels were mostly subtle. Here we reveal an aberrant global pattern of gene expression, characterized predominantly by higher levels of expression of activity-dependent genes, and anomalous alternative splicing events, specifically in response to neuronal activity in a mouse model for RTT. Notably, the specific splicing modalities of intron retention and exon skipping displayed a significant bias toward increased retained introns and skipped exons, respectively, in the RTT brain compared with the WT brain. Furthermore, these aberrations occur in conjunction with higher seizure susceptibility in response to neuronal activity in RTT mice. Our findings advance the concept that normal MeCP2 functioning is required for fine-tuning the robust and immediate changes in gene transcription and for proper regulation of alternative splicing induced in response to neuronal stimulation.}, } @article {pmid29769329, year = {2018}, author = {Tucker, DF and Sullivan, JT and Mattia, KA and Fisher, CR and Barnes, T and Mabila, MN and Wilf, R and Sulli, C and Pitts, M and Payne, RJ and Hall, M and Huston-Paterson, D and Deng, X and Davidson, E and Willis, SH and Doranz, BJ and Chambers, R and Rucker, JB}, title = {Isolation of state-dependent monoclonal antibodies against the 12-transmembrane domain glucose transporter 4 using virus-like particles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4990-E4999}, pmid = {29769329}, issn = {1091-6490}, support = {R43 DC010105/DC/NIDCD NIH HHS/United States ; R43 GM113556/GM/NIGMS NIH HHS/United States ; R44 DC010105/DC/NIDCD NIH HHS/United States ; R44 GM113556/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*immunology/*metabolism ; Chickens ; Epitope Mapping ; Glucose Transporter Type 4/chemistry/genetics/*immunology/*metabolism ; HEK293 Cells ; Humans ; Leukemia Virus, Murine/genetics ; Models, Molecular ; Protein Domains ; Vaccines, Virus-Like Particle/chemistry/*immunology ; }, abstract = {The insulin-responsive 12-transmembrane transporter GLUT4 changes conformation between an inward-open state and an outward-open state to actively facilitate cellular glucose uptake. Because of the difficulties of generating conformational mAbs against complex and highly conserved membrane proteins, no reliable tools exist to measure GLUT4 at the cell surface, follow its trafficking, or detect the conformational state of the protein. Here we report the isolation and characterization of conformational mAbs that recognize the extracellular and intracellular domains of GLUT4, including mAbs that are specific for the inward-open and outward-open states of GLUT4. mAbs against GLUT4 were generated using virus-like particles to present this complex membrane protein in its native conformation and using a divergent host species (chicken) for immunization to overcome immune tolerance. As a result, the isolated mAbs recognize conformational epitopes on native GLUT4 in cells, with apparent affinities as high as 1 pM and with specificity for GLUT4 across the human membrane proteome. Epitope mapping using shotgun mutagenesis alanine scanning across the 509 amino acids of GLUT4 identified the binding epitopes for mAbs specific for the states of GLUT4 and allowed the comprehensive identification of the residues that functionally control the GLUT4 inward-open and outward-open states. The mAbs identified here will be valuable molecular tools for monitoring GLUT4 structure, function, and trafficking, for differentiating GLUT4 conformational states, and for the development of novel therapeutics for the treatment of diabetes.}, } @article {pmid29769328, year = {2018}, author = {Yang, GY}, title = {Proinflammatory enzyme soluble epoxide hydrolase bridges obesity to colonic inflammation and potential carcinogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {5827-5828}, pmid = {29769328}, issn = {1091-6490}, support = {R01 CA164041/CA/NCI NIH HHS/United States ; R01 CA172431/CA/NCI NIH HHS/United States ; }, mesh = {Carcinogenesis ; Colon ; *Epoxide Hydrolases ; Humans ; Inflammation ; *Obesity ; }, } @article {pmid29769327, year = {2018}, author = {Reguera, G}, title = {Biological electron transport goes the extra mile.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5632-5634}, pmid = {29769327}, issn = {1091-6490}, mesh = {*Electron Transport ; *Electrons ; }, } @article {pmid29769149, year = {2018}, author = {Asfaw, LS and Ayanto, SY and Gurmamo, FL}, title = {Hypertension and its associated factors in Hosanna town, Southern Ethiopia: community based cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {306}, pmid = {29769149}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Humans ; Hypertension/*epidemiology ; Male ; Marital Status ; Middle Aged ; Prevalence ; Sex Factors ; }, abstract = {OBJECTIVES: This study was conducted to determine the prevalence of hypertension and its associated factors among residents of Hosanna town in Hadiya Zone.

RESULTS: The overall prevalence of hypertension was 30% among the study participants. Out of the study participants who were identified as being hypertensive, only 24.6% knew their hypertensive status. The odds of being hypertensive is significantly higher among males when compared to females (adjusted odds ratio (AOR) 1.9, confidence interval (CI) 1.14-3.23) and married participants as compared to their unmarried counterparts (AOR 4.1; CI 1.10-16.18). High prevalence and increased risks for hypertension were noted among the study participants in the study area. The experiences of aerobic physical activities were reported only in 22.9% of the study participants. These evidences may suggest the need for urgent interventions.}, } @article {pmid29769129, year = {2018}, author = {Zhang, Q}, title = {A powerful nonparametric method for detecting differentially co-expressed genes: distance correlation screening and edge-count test.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {58}, pmid = {29769129}, issn = {1752-0509}, support = {None//Arkansas Biosciences Institute/ ; }, abstract = {BACKGROUND: Differential co-expression analysis, as a complement of differential expression analysis, offers significant insights into the changes in molecular mechanism of different phenotypes. A prevailing approach to detecting differentially co-expressed genes is to compare Pearson's correlation coefficients in two phenotypes. However, due to the limitations of Pearson's correlation measure, this approach lacks the power to detect nonlinear changes in gene co-expression which is common in gene regulatory networks.

RESULTS: In this work, a new nonparametric procedure is proposed to search differentially co-expressed gene pairs in different phenotypes from large-scale data. Our computational pipeline consisted of two main steps, a screening step and a testing step. The screening step is to reduce the search space by filtering out all the independent gene pairs using distance correlation measure. In the testing step, we compare the gene co-expression patterns in different phenotypes by a recently developed edge-count test. Both steps are distribution-free and targeting nonlinear relations. We illustrate the promise of the new approach by analyzing the Cancer Genome Atlas data and the METABRIC data for breast cancer subtypes.

CONCLUSIONS: Compared with some existing methods, the new method is more powerful in detecting nonlinear type of differential co-expressions. The distance correlation screening can greatly improve computational efficiency, facilitating its application to large data sets.}, } @article {pmid29769118, year = {2018}, author = {Beikzadeh, B and Nikbakht Brujeni, G}, title = {Protection against neonatal enteric colibacillosis employing E. Coli-derived outer membrane vesicles in formulation and without vitamin D3.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {302}, pmid = {29769118}, issn = {1756-0500}, support = {32/6/7502015//University of Tehran/ ; }, mesh = {Animals ; Animals, Newborn ; Bacterial Outer Membrane Proteins ; Cholecalciferol/*pharmacology ; Enterotoxigenic Escherichia coli/*immunology ; Escherichia coli Infections/*prevention & control ; Escherichia coli Vaccines/*immunology ; Female ; *Immunization ; Intestinal Diseases/*prevention & control ; Male ; Mice ; Mice, Inbred BALB C ; }, abstract = {OBJECTIVE: Enterotoxigenic Escherichia Coli (ETEC) is the cause of diarrhea and even death in humans and offspring of animals. Outer membrane vesicles (OMVs) of the ETEC was prepared and its potential as a vaccine candidate against enteric colibacillosis in neonatal mice was evaluated. Dam mice intradermally injected with ETEC-derived OMVs and OMVs plus an active form of vitamin D3 (avD3). Mucosal and systemic immune responses in mice and passive immunity protection against ETEC lethality in their offspring was investigated.

RESULTS: Immunization of adult mice via ETEC-derived OMV alone and in formulation with avD3 protect offspring from ETEC-induced lethality. Nevertheless, avD3 did not indicate a positive effect on mucosal and systemic immune responses. Only the combination of OMV plus avD3 elicited a significant (P < 0.05) increase in the level of specific IgA antibodies in serum.}, } @article {pmid29769111, year = {2018}, author = {Abraha, TH and Demoz, AT and Moges, HG and Ahmmed, AN}, title = {Predictors of back disorder among Almeda textile factory workers, North Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {304}, pmid = {29769111}, issn = {1756-0500}, support = {2292/07/07/07//College of Medicine and Health Sciences, University of Gondar/ ; }, mesh = {Adult ; Back Pain/*epidemiology ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Musculoskeletal Diseases/*epidemiology ; Occupational Diseases/*epidemiology ; Textile Industry/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVES: To guide the development of targeted interventions for the prevention of work-related back pain, this manuscript estimates the prevalence of back pain and its association with a variety of risk factors among Almeda textile factory production works from March to April 2015. An institutional-based cross-sectional study was carried out in Almeda textile factory, North Ethiopia. Randomly selected workers were administered a structured questionnaire about their socio-economic status, lifestyle, working conditions, back pain and selected risk factors. The data was entered to Epi Info 3.5.4 version and analyzed using SPSS version 16. Descriptive statistics were done to characterize the study participants. Bivariate and multiple logistic regressions were fitted to control confounding variables. Adjusted odds ratio with 95% confidence intervals was computed.

RESULTS: The prevalence of work-related musculoskeletal disorders was 53.1%. Gender, age, years of service, lack of physical activity, unavailability of adjustable chair, work-load and poor light were significantly associated with increased risk of back pain. The high prevalence of work-related back pain disorder implies that; habit of doing physical exercise, availing adjustable chair and light at the working place, are key issues which require specific interventions.}, } @article {pmid29769110, year = {2018}, author = {Ngu, RC and Choukem, SP and Dimala, CA and Ngu, JN and Monekosso, GL}, title = {Prevalence and determinants of selected cardio-metabolic risk factors among people living with HIV/AIDS and receiving care in the South West Regional Hospitals of Cameroon: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {305}, pmid = {29769110}, issn = {1756-0500}, mesh = {Adult ; Aged ; *Antiretroviral Therapy, Highly Active ; Cameroon ; Comorbidity ; Cross-Sectional Studies ; Diabetes Mellitus/*epidemiology ; Female ; HIV Infections/drug therapy/*epidemiology ; Humans ; Hypertension/*epidemiology ; Male ; Middle Aged ; Obesity/*epidemiology ; Prevalence ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: Metabolic disorders and cardiovascular risk factors are not routinely assessed in the care of HIV patients in developing countries, known to have the highest disease burden. We described the prevalence and factors associated with major cardio-metabolic risk factors (obesity, diabetes and hypertension) in HIV/AIDS patients.

RESULTS: The prevalence of diabetes, hypertension and obesity were 11.3% (95% CI 8.10-15.43), 24.8% (95% CI 20.1-30.0) and 14.5% (95% CI 11.1-19.3) respectively. Central obesity and high alcohol intake were the factors significantly associated with diabetes mellitus, while central obesity and overweight/obesity were significantly associated with having hypertension. Short duration of antiretroviral therapy was the significant predisposing factor for obesity. On multivariate analyses, the only association observed was between central obesity and diabetes (Adjusted OR 2.52, 95% CI 1.01-6.30, P = 0.048). Conclusively, DM, HTN and obesity are highly prevalent in HIV/AIDS patients in the SWR hospitals of Cameroon, with that of DM and obesity being higher than that seen in the general population while that of HTN equaling that of the general population. Awareness of these data among clinicians involved in the management of these patients should be emphasized.}, } @article {pmid29769094, year = {2018}, author = {Paemanee, A and Hitakarun, A and Roytrakul, S and Smith, DR}, title = {Screening of melatonin, α-tocopherol, folic acid, acetyl-L-carnitine and resveratrol for anti-dengue 2 virus activity.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {307}, pmid = {29769094}, issn = {1756-0500}, support = {BRG6080006//Thailand Research Fund/ ; IRN60W0002//Thailand Research Fund/ ; }, mesh = {Acetylcarnitine/*pharmacology ; Antiviral Agents/*pharmacology ; Dengue/*drug therapy ; Dengue Virus/*drug effects ; Folic Acid/*pharmacology ; HEK293 Cells ; Hep G2 Cells ; Humans ; Melatonin/*pharmacology ; Resveratrol ; Stilbenes/*pharmacology ; alpha-Tocopherol/*pharmacology ; }, abstract = {OBJECTIVE: Infections with the mosquito transmitted dengue virus (DENV) are a significant public health burden in many parts of the world. Despite the introduction of a commercial vaccine in some parts of the world, the majority of the populations at risk of infection remain unprotected against this disease, and there is currently no treatment for DENV infection. Natural compounds offer the prospect of cheap and sustainable therapeutics to reduce the disease burden during infection, and thus potentially alleviate the risk of more severe disease. This study evaluated the potential anti-DENV 2 activity of five natural compounds namely melatonin, α-tocopherol, folic acid, acetyl-L-carnitine and resveratrol in two different cell lines.

RESULTS: Screening of the compounds showed that one compound (acetyl-L-carnitine) showed no effect on DENV infection, three compounds (melatonin, α-tocopherol and folic acid) slightly increased levels of infection, while the 5th compound, resveratrol, showed some limited anti-DENV activity, with resveratrol reducing virus output with an EC50 of less than 25 μM. These results suggest that some commonly taken natural compounds may have beneficial effects on DENV infection, but that others may potentially add to the disease burden.}, } @article {pmid29769093, year = {2018}, author = {Irfan, O and Khan, H and Khan, Z and Ashraf, A and Ahmed, R and Khan, JA and Zubairi, ABS}, title = {Granulomatosis with polyangiitis: a 17 year experience from a tertiary care hospital in Pakistan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {303}, pmid = {29769093}, issn = {1756-0500}, mesh = {Adult ; Antibodies, Antineutrophil Cytoplasmic/*blood ; Female ; *Granulomatosis with Polyangiitis/blood/complications/pathology/physiopathology ; Humans ; Male ; Middle Aged ; Pakistan ; Retrospective Studies ; Tertiary Care Centers ; }, abstract = {OBJECTIVE: Granulomatosis with Polyangiitis (GPA) is an autoimmune, multi-system, small and medium vessel vasculitis with granulomatous inflammation. Aim of this study was to assess the clinical and radiological presentations of patients with GPA amongst the Pakistani population. It is a single centre retrospective single observation study.

RESULTS: Study was conducted at the Aga Khan University Hospital, Karachi with records were reviewed from January 2000 to December 2017. Definitive diagnosis was made using a combination of serological anti-neutrophil cytoplasmic antibody (ANCA) testing along with the clinical and radiological presentation. A total of 51 patients met the diagnostic criteria in the time frame of the study. There were 23 males and 28 females with mean age of 44.0 ± 17.8 years on presentation. Arthritis was the most common symptom present in 41.2% of the cases followed by cough in 32.0%. Sixteen patients showed pulmonary infiltrates on chest X-ray. C-ANCA was positive in all of the patients compared with 21.6% p-ANCA positivity. A total of 13 biopsies were done. The median Birmingham Vasculitis Activity Score was 12. We report a 17.6% mortality rate with 5 deaths occurring due to respiratory failure. GPA is a diagnostic challenge leading to late diagnosis which can contribute to significant morbidity and mortality specially in the Third World.}, } @article {pmid29769044, year = {2018}, author = {Faust, K and Xie, Q and Han, D and Goyle, K and Volynskaya, Z and Djuric, U and Diamandis, P}, title = {Visualizing histopathologic deep learning classification and anomaly detection using nonlinear feature space dimensionality reduction.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {173}, pmid = {29769044}, issn = {1471-2105}, abstract = {BACKGROUND: There is growing interest in utilizing artificial intelligence, and particularly deep learning, for computer vision in histopathology. While accumulating studies highlight expert-level performance of convolutional neural networks (CNNs) on focused classification tasks, most studies rely on probability distribution scores with empirically defined cutoff values based on post-hoc analysis. More generalizable tools that allow humans to visualize histology-based deep learning inferences and decision making are scarce.

RESULTS: Here, we leverage t-distributed Stochastic Neighbor Embedding (t-SNE) to reduce dimensionality and depict how CNNs organize histomorphologic information. Unique to our workflow, we develop a quantitative and transparent approach to visualizing classification decisions prior to softmax compression. By discretizing the relationships between classes on the t-SNE plot, we show we can super-impose randomly sampled regions of test images and use their distribution to render statistically-driven classifications. Therefore, in addition to providing intuitive outputs for human review, this visual approach can carry out automated and objective multi-class classifications similar to more traditional and less-transparent categorical probability distribution scores. Importantly, this novel classification approach is driven by a priori statistically defined cutoffs. It therefore serves as a generalizable classification and anomaly detection tool less reliant on post-hoc tuning.

CONCLUSION: Routine incorporation of this convenient approach for quantitative visualization and error reduction in histopathology aims to accelerate early adoption of CNNs into generalized real-world applications where unanticipated and previously untrained classes are often encountered.}, } @article {pmid29769032, year = {2018}, author = {Telles, GP and Araújo, GS and Walter, MEMT and Brigido, MM and Almeida, NF}, title = {Live neighbor-joining.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {172}, pmid = {29769032}, issn = {1471-2105}, abstract = {BACKGROUND: In phylogenetic reconstruction the result is a tree where all taxa are leaves and internal nodes are hypothetical ancestors. In a live phylogeny, both ancestral and living taxa may coexist, leading to a tree where internal nodes may be living taxa. The well-known Neighbor-Joining heuristic is largely used for phylogenetic reconstruction.

RESULTS: We present Live Neighbor-Joining, a heuristic for building a live phylogeny. We have investigated Live Neighbor-Joining on datasets of viral genomes, a plausible scenario for its application, which allowed the construction of alternative hypothesis for the relationships among virus that embrace both ancestral and descending taxa. We also applied Live Neighbor-Joining on a set of bacterial genomes and to sets of images and texts. Non-biological data may be better explored visually when their relationship in terms of content similarity is represented by means of a phylogeny.

CONCLUSION: Our experiments have shown interesting alternative phylogenetic hypothesis for RNA virus genomes, bacterial genomes and alternative relationships among images and texts, illustrating a wide range of scenarios where Live Neighbor-Joining may be used.}, } @article {pmid29769016, year = {2018}, author = {Zeng, X and Kwok, JS and Yang, KY and Leung, KS and Shi, M and Yang, Z and Yam, WC and Tsui, SK}, title = {Whole genome sequencing data of 1110 Mycobacterium tuberculosis isolates identifies insertions and deletions associated with drug resistance.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {365}, pmid = {29769016}, issn = {1471-2164}, support = {09080302//Health and Medical Research Fund/ ; 11100282//Health and Medical Research Fund/ ; 13120432//Health and Medical Research Fund/ ; }, mesh = {DNA Repair/genetics ; Drug Resistance, Multiple, Bacterial/*genetics ; Humans ; *INDEL Mutation ; Mycobacterium tuberculosis/*drug effects/*genetics/physiology ; *Whole Genome Sequencing ; }, abstract = {BACKGROUND: Drug resistance in Mycobacterium tuberculosis (MTB) is one of the major challenges in tuberculosis (TB) treatment. However, known mutations cannot explain all of the cases of resistance and little research has focused on the relationship between insertions / deletions (indels) and drug resistance.

RESULTS: Here, we retrieved whole genome sequencing data of 743 drug-resistant MTB strains and 367 pan-susceptible strains from TB patients from the public domain to identify novel genomic markers of drug resistance. A total of 20 region markers containing genes and intergenic regions (IGRs) with significant statistical correlation with antibiotic resistance were revealed, four of which have been previously reported to be associated with drug resistance. In addition, 83 point markers containing frameshift (FS) mutations and IGR indels were also identified independently based on differences in their incidence rates between drug-sensitive and -resistant strains. Among the 83 point markers, eight indels were detected in known drug-associated genes or IGRs. Furthermore, the overlap between 20 region markers and 83 point markers further indicated their associations with drug resistance. The markers identified were involved in essential bacterial metabolic functions, including cell wall and transmembrane transporter functions. A strong correlation between FS mutations and mutations in DNA repair genes including I21V in alkA, R48G in mutT4 and P2R in nth was also found.

CONCLUSIONS: This study identified a set of novel genetic markers with FS mutations and IGR indels associated with MTB drug resistance, which greatly broadens the pool of mutations related to MTB drug resistance. This insight may be important in identifying novel mechanisms of drug resistance in MTB.}, } @article {pmid29769015, year = {2018}, author = {Tong, KJ and Duchêne, DA and Duchêne, S and Geoghegan, JL and Ho, SYW}, title = {A comparison of methods for estimating substitution rates from ancient DNA sequence data.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {70}, pmid = {29769015}, issn = {1471-2148}, support = {FT160100167//Australian Research Council/International ; }, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Computer Simulation ; *DNA, Ancient ; Evolution, Molecular ; Genome, Mitochondrial ; Genomics/*methods ; Horses ; Mutation/*genetics ; Phylogeny ; Time Factors ; Uncertainty ; Vertebrates/*genetics ; }, abstract = {BACKGROUND: Phylogenetic analysis of DNA from modern and ancient samples allows the reconstruction of important demographic and evolutionary processes. A critical component of these analyses is the estimation of evolutionary rates, which can be calibrated using information about the ages of the samples. However, the reliability of these rate estimates can be negatively affected by among-lineage rate variation and non-random sampling. Using a simulation study, we compared the performance of three phylogenetic methods for inferring evolutionary rates from time-structured data sets: regression of root-to-tip distances, least-squares dating, and Bayesian inference. We also applied these three methods to time-structured mitogenomic data sets from six vertebrate species.

RESULTS: Our results from 12 simulation scenarios show that the three methods produce reliable estimates when the substitution rate is high, rate variation is low, and samples of similar ages are not all grouped together in the tree (i.e., low phylo-temporal clustering). The interaction of these factors is particularly important for least-squares dating and Bayesian estimation of evolutionary rates. The three estimation methods produced consistent estimates of rates across most of the six mitogenomic data sets, with sequence data from horses being an exception.

CONCLUSIONS: We recommend that phylogenetic studies of ancient DNA sequences should use multiple methods of inference and test for the presence of temporal signal, among-lineage rate variation, and phylo-temporal clustering in the data.}, } @article {pmid29768649, year = {2018}, author = {Liefting, M and Hoedjes, KM and Le Lann, C and Smid, HM and Ellers, J}, title = {Selection for associative learning of color stimuli reveals correlated evolution of this learning ability across multiple stimuli and rewards.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, pmid = {29768649}, issn = {1558-5646}, abstract = {We are only starting to understand how variation in cognitive ability can result from local adaptations to environmental conditions. A major question in this regard is to what extent selection on cognitive ability in a specific context affects that ability in general through correlated evolution. To address this question, we performed artificial selection on visual associative learning in female Nasonia vitripennis wasps. Using appetitive conditioning in which a visual stimulus was offered in association with a host reward, the ability to learn visual associations was enhanced within 10 generations of selection. To test for correlated evolution affecting this form of learning, the ability to readily form learned associations in females was also tested using an olfactory instead of a visual stimulus in the appetitive conditioning. Additionally, we assessed whether the improved associative learning ability was expressed across sexes by color-conditioning males with a mating reward. Both females and males from the selected lines consistently demonstrated an increased associative learning ability compared to the control lines, independent of learning context or conditioned stimulus. No difference in relative volume of brain neuropils was detected between the selected and control lines.}, } @article {pmid29767724, year = {2018}, author = {Magnabosco, C and Timmers, PHA and Lau, MCY and Borgonie, G and Linage-Alvarez, B and Kuloyo, O and Alleva, R and Kieft, TL and Slater, GF and van Heerden, E and Sherwood Lollar, B and Onstott, TC}, title = {Fluctuations in populations of subsurface methane oxidizers in coordination with changes in electron acceptor availability.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy089}, pmid = {29767724}, issn = {1574-6941}, abstract = {The concentrations of electron donors and acceptors in the terrestrial subsurface biosphere fluctuate due to migration and mixing of subsurface fluids, but the mechanisms and rates at which microbial communities respond to these changes are largely unknown. Subsurface microbial communities exhibit long cellular turnover times and are often considered relatively static-generating just enough ATP for cellular maintenance. Here, we investigated how subsurface populations of CH4 oxidizers respond to changes in electron acceptor availability by monitoring the biological and geochemical composition in a 1339 m-below-land-surface (mbls) fluid-filled fracture over the course of both longer (2.5 year) and shorter (2-week) time scales. Using a combination of metagenomic, metatranscriptomic, and metaproteomic analyses, we observe that the CH4 oxidizers within the subsurface microbial community change in coordination with electron acceptor availability over time. We then validate these findings through a series of 13C-CH4 laboratory incubation experiments, highlighting a connection between composition of subsurface CH4 oxidizing communities and electron acceptor availability.}, } @article {pmid29767715, year = {2018}, author = {Táncsics, A and Szalay, AR and Farkas, M and Benedek, T and Szoboszlay, S and Szabó, I and Lueders, T}, title = {Stable isotope probing of hypoxic toluene degradation at the Siklós aquifer reveals prominent role of Rhodocyclaceae.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, pmid = {29767715}, issn = {1574-6941}, abstract = {The availability of oxygen is often a limiting factor for the degradation of aromatic hydrocarbons in subsurface environments. However, while both aerobic and anaerobic degraders have been intensively studied, degradation betwixt, under micro- or hypoxic conditions has rarely been addressed. It is speculated that in environments with limited, but sustained oxygen supply, such as in the vicinity of groundwater monitoring wells, hypoxic degradation may take place. A large diversity of subfamily I.2.C extradiol dioxygenase genes has been previously detected in a BTEX-contaminated aquifer in Hungary. Older literature suggests that such catabolic potentials could be associated to hypoxic degradation. Bacterial communities dominated by members of the Rhodocyclaceae were found, but the majority of the detected C23O genotypes could not be affiliated to any known bacterial degrader lineages. To address this, a stable isotope probing (SIP) incubation of site sediments with 13C7-toluene was performed under microoxic conditions. A combination of 16S rRNA gene amplicon sequencing and T-RFLP fingerprinting of C23O genes from SIP gradient fractions revealed the central role of degraders within the Rhodocyclaceae in hypoxic toluene degradation. The main assimilators of 13C were identified as members of the genera Quatrionicoccus and Zoogloea, and a yet uncultured group of the Rhodocyclaceae.}, } @article {pmid29767712, year = {2018}, author = {Buelow, E and Bayjanov, JR and Majoor, E and Willems, RJ and Bonten, MJ and Schmitt, H and van Schaik, W}, title = {Limited influence of hospital wastewater on the microbiome and resistome of wastewater in a community sewerage system.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy087}, pmid = {29767712}, issn = {1574-6941}, abstract = {Effluents from wastewater treatment plants (WWTPs) have been proposed to act as point sources of antibiotic-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs) in the environment. Hospital sewage may contribute to the spread of ARB and ARGs as it contains the feces and urine of hospitalized patients, who are more frequently colonized with multi-drug resistant bacteria than the general population. However, whether hospital sewage noticeably contributes to the quantity and diversity of ARGs in the general sewerage system has not yet been determined.Here, we employed culture-independent techniques, namely 16S rRNA gene sequencing and nanolitre-scale quantitative PCRs, to assess the role of hospital effluent as a point source of ARGs in the sewerage system, through comparing microbiota composition and levels of ARGs in hospital sewage with WWTP influent with and without hospital sewage.Compared to other sites, hospital sewage was richest in human-associated bacteria and contained the highest relative levels of ARGs. Yet, the relative abundance of ARGs was comparable in the influent of WWTPs with and without hospital sewage, suggesting that hospitals do not contribute importantly to the quantity and diversity of ARGs in the investigated sewerage system.}, } @article {pmid29767710, year = {2018}, author = {Smith, HJ and Dieser, M and McKnight, DM and SanClements, MD and Foreman, CM}, title = {Relationship between dissolved organic matter quality and microbial community composition across polar glacial environments.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy090}, pmid = {29767710}, issn = {1574-6941}, abstract = {Vast expanses of Earth's surface are covered by ice, with microorganisms in these systems affecting local and global biogeochemical cycles. We examined microbial assemblages from habitats fed by glacial meltwater within the McMurdo Dry Valleys, Antarctica and on the west Greenland Ice Sheet (GrIS), evaluating potential physicochemical factors explaining trends in community structure. Microbial assemblages present in the different Antarctic dry valley habitats were dominated by Sphingobacteria andFlavobacteria, while Gammaproteobacteria and Sphingobacteria prevailed in west GrIS supraglacial environments. Microbial assemblages clustered by location (Canada Glacier, Cotton Glacier and west GrIS) and were separated by habitat type (i.e. ice, cryoconite holes, supraglacial lakes, sediment and stream water). Community dissimilarities were strongly correlated with dissolved organic matter (DOM) quality. Microbial meltwater assemblages were most closely associated with different protein-like components of the DOM pool. Microbes in environments with mineral particles (i.e. stream sediments and cryoconite holes) were linked to DOM containing more humic-like fluorescence. Our results demonstrate the establishment of distinct microbial communities within ephemeral glacial meltwater habitats, with DOM-microbe interactions playing an integral role in shaping communities on local and polar spatial scales.}, } @article {pmid29767618, year = {2018}, author = {Lim, SJ and Ten, LN and Kim, BO and Kang, IK and Jung, HY}, title = {Hymenobacter pedocola sp. nov., a novel bacterium isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2242-2248}, doi = {10.1099/ijsem.0.002818}, pmid = {29767618}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain S12-2-1T was isolated from a soil sample collected in the Gyeongsangnam-do province of the Republic of Korea. The isolate is a Gram-stain-negative, aerobic, short, rod-shaped bacterium, and its colonies are red to pink in colour. Analysis of the 16S rRNA gene identified strain S12-2-1T as a member of the genus Hymenobacter in the family Cytophagaceae, with high levels of 16S rRNA gene sequence similarity to Hymenobacter arizonensis OR362-8T (97.7 %), Hymenobacter sedentarius DG5BT (97.4 %) and Hymenobacter humi DG31AT (97.2 %). The isolate was positive for catalase and oxidase, but negative for acid production from glucose. The growth of strain S12-2-1T was supported at 4-30 °C, pH 7-10 and in the presence of 0-0.5 % NaCl. Strain S12-2-1T contained menaquinone-7 as the predominant respiratory quinone, sym-homospermidine as the major polyamine and iso-C15 : 0, anteiso-C15 : 0 and summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) as the major fatty acids. Phosphatidylethanolamine was the major polar lipid. The genomic DNA G+C content was 58.7 mol%. Phenotypic and chemotaxonomic data supported the assignment of the isolate to the genus Hymenobacter. However, strain S12-2-1T exhibited a relatively low level of DNA-DNA relatedness with H. humi (31.7 %), H. arizonensis (24.4 %) and H. sedentarius (21.3 %). Based on its phenotypic and genotypic properties, along with its phylogenetic distinctiveness, strain S12-2-1T should be considered a novel species in the genus Hymenobacter, for which the name Hymenobacter pedocola sp. nov. is proposed. The type strain is S12-2-1T (=KCTC 52730T=JCM 32198T).}, } @article {pmid29767617, year = {2018}, author = {Yu, Z and Cao, Y and Zhou, G and Yin, J and Qiu, J}, title = {Mangrovicoccus ximenensis gen. nov., sp. nov., isolated from mangrove forest sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2172-2177}, doi = {10.1099/ijsem.0.002796}, pmid = {29767617}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizophoraceae ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Wetlands ; }, abstract = {A Gram-strain-negative, coccoid bacterium, lacking bacteriochlorophyll, designated strain T1lg56T, was isolated from a sediment sample collected from Ximen island mangrove forest, Zhejiang province, China. Cells were halotolerant, and catalase- and oxidase-positive. Growth was observed at 18-42 °C (optimum, 35 °C), at pH 6.0-9.5 (optimum, pH 6.5) and in the presence of 0-15 % (w/v) NaCl (optimum, 2-5 %). The major cellular fatty acids were C18 : 1ω7c and C16 : 0. The polar lipid profile of strain T1lg56T consisted of phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmonomethylethanolamine, two unidentified phospholipids and five unidentified lipids. Ubiquinone-10 was the predominant respiratory quinone. The assimilation of the substrates in the API 20NE kit was positive in strain T1lg56T. The DNA G+C content of strain T1lg56T was 67.2 mol%. 16S rRNA gene sequence analysis indicated that strain T1lg56T was a member of family Rhodobacteraceae and was closely related to Poseidonocella pacifica KMM 9010T, with 95.7 % similarity to the type strain. Phylogenetic analysis showed that strain T1lg56T formed a separate evolutionary branch, and was parallel to other related genera of Rhodobacteraceae. Its phylogenetic distinctiveness and distinguishing phenotypic characteristics supported that strain T1lg56T represents a novel genus of the family Rhodobacteraceae, for which the name Mangrovicoccus ximenensis gen. nov., sp. nov. is proposed. The type strain is T1lg56T (=CCTCC AB 2016238T=KCTC 52623T).}, } @article {pmid29767461, year = {2018}, author = {Briolat, ES and Zagrobelny, M and Olsen, CE and Blount, JD and Stevens, M}, title = {Sex differences but no evidence of quantitative honesty in the warning signals of six-spot burnet moths (Zygaena filipendulae L.).}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, pmid = {29767461}, issn = {1558-5646}, abstract = {The distinctive black and red wing pattern of six-spot burnet moths (Zygaena filipendulae, L.) is a classic example of aposematism, advertising their potent cyanide-based defences. While such warning signals provide a qualitatively honest signal of unprofitability, the evidence for quantitative honesty, whereby variation in visual traits could provide accurate estimates of individual toxicity, is more equivocal. Combining measures of cyanogenic glucoside content and wing color from the perspective of avian predators, we investigate the relationship between coloration and defences in Z. filipendulae, to test signal honesty both within and across populations. There were no significant relationships between mean cyanogenic glucoside concentration and metrics of wing coloration across populations in males, yet in females higher cyanogenic glucoside levels were associated with smaller and lighter red forewing markings. Trends within populations were similarly inconsistent with quantitative honesty, and persistent differences between the sexes were apparent: larger females, carrying a greater total cyanogenic glucoside load, displayed larger but less conspicuous markings than smaller males, according to several color metrics. The overall high aversiveness of cyanogenic glucosides and fluctuations in color and toxin levels during an individual's lifetime may contribute to these results, highlighting generally important reasons why signal honesty should not always be expected in aposematic species.}, } @article {pmid29766650, year = {2018}, author = {Chaverri, G and Ancillotto, L and Russo, D}, title = {Social communication in bats.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1938-1954}, doi = {10.1111/brv.12427}, pmid = {29766650}, issn = {1469-185X}, abstract = {Bats represent one of the most diverse mammalian orders, not only in terms of species numbers, but also in their ecology and life histories. Many species are known to use ephemeral and/or unpredictable resources that require substantial investment to find and defend, and also engage in social interactions, thus requiring significant levels of social coordination. To accomplish these tasks, bats must be able to communicate; there is now substantial evidence that demonstrates the complexity of bat communication and the varied ways in which bats solve some of the problems associated with their unique life histories. However, while the study of communication in bats is rapidly growing, it still lags behind other taxa. Here we provide a comprehensive overview of communication in bats, from the reasons why they communicate to the diversity and application of different signal modalities. The most widespread form of communication is the transmission of a signaller's characteristics, such as species identity, sex, individual identity, group membership, social status and body condition, and because many species of bats can rely little on vision due to their nocturnal lifestyles, it is assumed that sound and olfaction are particularly important signalling modes. For example, research suggests that secretions from specialized glands, often in combination with urine and saliva, are responsible for species recognition in several species. These olfactory signals may also convey information about sex and colony membership. Olfaction may be used in combination with sound, particularly in species that emit constant frequency (CF) echolocation calls, to recognize conspecifics from heterospecifics, yet their simple structure and high frequency do not allow much information of individual identity to be conveyed over long distances. By contrast, social calls may encode a larger number of cues of individual identity, and their lower frequencies increase their range of detection. Social calls are also known to deter predators, repel competitors from foraging patches, attract group mates to roost sites, coordinate foraging activities, and are used during courtship. In addition to sound, visual displays such as wing flapping or hovering may be used during courtship, and swarming around roost sites may serve as a visual cue of roost location. However, visual communication in bats still remains a poorly studied signal modality. Finally, the most common form of tactile communication known in bats is social grooming, which may be used to signal reproductive condition, but also to facilitate and strengthen cooperative interactions. Overall, this review demonstrates the rapid advances made in the study of bat social communication during recent years, and also identifies topics that require further study, particularly those that may allow us to understand adaptation to rapidly changing environmental conditions.}, } @article {pmid29766494, year = {2018}, author = {Simon, A and Duranton, M}, title = {Digest: Demographic inferences accounting for selection at linked sites†.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1330-1332}, doi = {10.1111/evo.13504}, pmid = {29766494}, issn = {1558-5646}, abstract = {Complex demography and selection at linked sites can generate spurious signatures of divergent selection. Unfortunately, many attempts at demographic inference consider overly simple models and neglect the effect of selection at linked sites. In this issue, Rougemont and Bernatchez (2018) applied an approximate Bayesian computation (ABC) framework that accounts for indirect selection to reveal a complex history of secondary contacts in Atlantic salmon (Salmo salar) that might explain a high rate of latitudinal clines in this species.}, } @article {pmid29766491, year = {2018}, author = {Kriesner, P and Hoffmann, AA}, title = {Rapid spread of a Wolbachia infection that does not affect host reproduction in Drosophila simulans cage populations.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13506}, pmid = {29766491}, issn = {1558-5646}, abstract = {Wolbachia endosymbionts that are maternally inherited can spread rapidly in host populations through inducing sterility in uninfected females, but some Wolbachia infections do not influence host reproduction yet still persist. These infections are particularly interesting because they likely represent mutualistic endosymbionts, spreading by increasing host fitness. Here, we document such a spread in the wAu infection of Drosophila simulans. By establishing multiple replicate cage populations, we show that wAu consistently increased from an intermediate frequency to near fixation, representing an estimated fitness advantage of around 20% for infected females. The effective population size in the cages was estimated from SNP markers to be around a few thousand individuals, precluding large effects of genetic drift in the populations. The exact reasons for the fitness advantage are unclear but viral protection and nutritional benefits are two possibilities.}, } @article {pmid29766489, year = {2018}, author = {Figueirido, B}, title = {Phenotypic disparity of the elbow joint in domestic dogs and wild carnivores.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13503}, pmid = {29766489}, issn = {1558-5646}, abstract = {In this article, I use geometric morphometrics in 2D from a sample of 366 elbow joints to quantify phenotypic disparity in domestic dog breeds, in wild canids, and across the order Carnivora. The elbow joint is a well-established morphological indicator of forearm motion and, by extension, of functional adaptations toward locomotor or predatory behavior in living carnivores. The study of the elbow joint in domestic dogs allows the exploration of potential convergences between (i) pursuit predators and fast-running dogs, and (ii) ambush predators and fighting breeds. The results indicate that elbow shape disparity among domestic dogs exceeds than in wolves; it is comparable to the disparity of wild Caninae, but is significantly lower than the one observed throughout Canidae and Carnivora. Moreover, fast-running and fighting breeds are not convergent in elbow joint shape with extreme pursuit and ambush wild carnivores, respectively. The role of artificial selection and developmental constraints in shaping limb phenotypic disparity through the extremely fast evolution of the domestic dog is discussed in the light of this new evidence.}, } @article {pmid29766233, year = {2018}, author = {Pala, C and Molari, M and Nizzoli, D and Bartoli, M and Viaroli, P and Manini, E}, title = {Environmental Drivers Controlling Bacterial and Archaeal Abundance in the Sediments of a Mediterranean Lagoon Ecosystem.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29766233}, issn = {1432-0991}, support = {CTM2007-28739-E//European Science Foundation (FR) EuroDeep-BIOFUN/ ; }, abstract = {The environmental factors controlling the abundance of Bacteria and Archaea in lagoon ecosystems are poorly understood. Here, an integrated physico-chemical, biogeochemical, and microbiological survey was applied in the Sacca di Goro lagoon (Po River Delta, Italy) to investigate the variation of bacterial and archaeal abundance, as assessed by Fluorescence In Situ Hybridization, along winter and summer environmental gradients. We hypothesised that bacterial and archaeal cells respond differentially to physico-chemical parameters of the sediment, which can be manifested in variations of total cells number. Our results suggest that Archaea are an important component of microbial communities (up to 20%) and they are also quite constant along the sediment depth investigated, while Bacteria tend to decrease in the subsurface sediments. The abiotic (i.e. temperature, ammonium, pH) and trophic parameters (i.e. chlorophyll a) explain differentially the variations of bacterial and archaeal distribution, and raise interesting questions about the ecological significance of the microbial composition in this area.}, } @article {pmid29765597, year = {2018}, author = {Greaves, M and Hughes, W}, title = {Cancer cell transmission via the placenta.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {106-115}, pmid = {29765597}, issn = {2050-6201}, abstract = {Cancer cells have a parasitic propensity in the primary host but their capacity to transit between individuals is severely restrained by two factors: a lack of a route for viable cell transfer and immune recognition in allogeneic, secondary recipients. Several examples of transmissible animal cancers are now recognised. In humans, the only natural route for transmission is via the haemochorial placenta which is permissive for cell traffic. There are three special examples of this occurring in utero: maternal to foetus, intraplacental twin to twin leukaemias and choriocarcinoma-extra-embryonic cells to mother. We discuss the rare circumstances under which such transmission occurs.}, } @article {pmid29765596, year = {2018}, author = {Boyden, SD and Pott, M and Starks, PT}, title = {An evolutionary perspective on night terrors.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {100-105}, pmid = {29765596}, issn = {2050-6201}, abstract = {Night terrors, also known as sleep terrors, are an early childhood parasomnia characterized by screams or cries, behavioral manifestations of extreme fear, difficulty waking and inconsolability upon awakening. The mechanism causing night terrors is unknown, and a consistently successful treatment has yet to be documented. Here, we argue that cultural practices have moved us away from an ultimate solution: cosleeping. Cosleeping is the norm for closely related primates and for humans in non-Western cultures. In recent years, however, cosleeping has been discouraged by the Western medical community. From an evolutionary perspective, cosleeping provides health and safety benefits for developing children. We discuss night terrors, and immediate and long-term health features, with respect to cosleeping, room-sharing and solitary sleeping. We suggest that cosleeping with children (≥1-year-old) may prevent night terrors and that, under certain circumstances, cosleeping with infants (≤11-months-old) is preferable to room-sharing, and both are preferable to solitary sleeping.}, } @article {pmid29765162, year = {2018}, author = {Furlong, R}, title = {Scrutinizing spliceosomes.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {401}, doi = {10.1038/s41576-018-0019-9}, pmid = {29765162}, issn = {1471-0064}, } @article {pmid29765128, year = {2018}, author = {}, title = {Aluminium producers promise a cleaner smelting pot.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {280}, doi = {10.1038/d41586-018-05158-1}, pmid = {29765128}, issn = {1476-4687}, } @article {pmid29765127, year = {2018}, author = {Cyranoski, D}, title = {Sacked Japanese biologist gets chance to retrain at Crick institute.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {288-289}, doi = {10.1038/d41586-018-05139-4}, pmid = {29765127}, issn = {1476-4687}, mesh = {*Academies and Institutes ; London ; Research Personnel/*education/*ethics ; Scientific Misconduct/*legislation & jurisprudence ; Tokyo ; Universities ; Workforce ; }, } @article {pmid29765126, year = {2018}, author = {Guglielmi, G}, title = {Wikipedia's top-cited scholarly articles - revealed.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {291-292}, doi = {10.1038/d41586-018-05161-6}, pmid = {29765126}, issn = {1476-4687}, mesh = {Animals ; *Astronomy ; *Bibliometrics ; Climate ; Datasets as Topic/statistics & numerical data ; Genes ; *Genetics ; Humans ; Internet/*statistics & numerical data ; Language ; Mice ; Minor Planets ; Moon ; Open Access Publishing ; Protein Interaction Maps ; }, } @article {pmid29765125, year = {2018}, author = {Gray, N and Le Bot, N and Heemels, MT}, title = {Regeneration.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {321}, doi = {10.1038/d41586-018-05155-4}, pmid = {29765125}, issn = {1476-4687}, mesh = {Cell Transformation, Neoplastic/pathology ; Health ; Humans ; Pancreas/growth & development ; Regeneration/*physiology ; *Regenerative Medicine ; Spinal Cord Injuries/pathology ; Spinal Cord Regeneration ; Stem Cell Transplantation ; Wound Healing/physiology ; }, } @article {pmid29765124, year = {2018}, author = {Hegglin, MI}, title = {Evidence of illegal emissions of ozone-depleting chemicals.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {317-318}, doi = {10.1038/d41586-018-05110-3}, pmid = {29765124}, issn = {1476-4687}, mesh = {Air Pollutants/analysis ; *Atmosphere ; Environmental Monitoring ; Ozone/*analysis ; }, } @article {pmid29765123, year = {2018}, author = {Bouwens, R}, title = {Distant galaxy formed stars only 250 million years after the Big Bang.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {312-313}, doi = {10.1038/d41586-018-05114-z}, pmid = {29765123}, issn = {1476-4687}, } @article {pmid29765122, year = {2018}, author = {Phillips, N}, title = {Australian budget delivers for science facilities and medical research.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {290}, doi = {10.1038/d41586-018-05119-8}, pmid = {29765122}, issn = {1476-4687}, mesh = {Australia ; Biomedical Research/*economics ; *Budgets ; Genomics/economics ; Humans ; Precision Medicine/economics ; Science/*economics ; }, } @article {pmid29765121, year = {2018}, author = {Tollefson, J}, title = {How science will suffer as US pulls out of Iran nuclear deal.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {287-288}, doi = {10.1038/d41586-018-05123-y}, pmid = {29765121}, issn = {1476-4687}, mesh = {*Cooperative Behavior ; International Cooperation/*legislation & jurisprudence ; Iran ; Nuclear Weapons/*legislation & jurisprudence ; Research/legislation & jurisprudence/*organization & administration/trends ; Research Personnel/*organization & administration ; United States ; Workforce ; }, } @article {pmid29765116, year = {2018}, author = {Du Toit, A}, title = {Passing on the electrons.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {394}, doi = {10.1038/s41579-018-0027-y}, pmid = {29765116}, issn = {1740-1534}, } @article {pmid29765001, year = {2018}, author = {Redish, AD and Kummerfeld, E and Morris, RL and Love, AC}, title = {Opinion: Reproducibility failures are essential to scientific inquiry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5042-5046}, pmid = {29765001}, issn = {1091-6490}, } @article {pmid29765000, year = {2018}, author = {Chen, T and Bilal, OR and Shea, K and Daraio, C}, title = {Harnessing bistability for directional propulsion of soft, untethered robots.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5698-5702}, pmid = {29765000}, issn = {1091-6490}, abstract = {In most macroscale robotic systems, propulsion and controls are enabled through a physical tether or complex onboard electronics and batteries. A tether simplifies the design process but limits the range of motion of the robot, while onboard controls and power supplies are heavy and complicate the design process. Here, we present a simple design principle for an untethered, soft swimming robot with preprogrammed, directional propulsion without a battery or onboard electronics. Locomotion is achieved by using actuators that harness the large displacements of bistable elements triggered by surrounding temperature changes. Powered by shape memory polymer (SMP) muscles, the bistable elements in turn actuate the robot's fins. Our robots are fabricated using a commercially available 3D printer in a single print. As a proof of concept, we show the ability to program a vessel, which can autonomously deliver a cargo and navigate back to the deployment point.}, } @article {pmid29764999, year = {2018}, author = {Xu, L and Chen, Y and Mayakonda, A and Koh, L and Chong, YK and Buckley, DL and Sandanaraj, E and Lim, SW and Lin, RY and Ke, XY and Huang, ML and Chen, J and Sun, W and Wang, LZ and Goh, BC and Dinh, HQ and Kappei, D and Winter, GE and Ding, LW and Ang, BT and Berman, BP and Bradner, JE and Tang, C and Koeffler, HP}, title = {Targetable BET proteins- and E2F1-dependent transcriptional program maintains the malignancy of glioblastoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5086-E5095}, pmid = {29764999}, issn = {1091-6490}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Drug Delivery Systems ; *E2F1 Transcription Factor/antagonists & inhibitors/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; *Glioblastoma/metabolism/pathology ; Humans ; Nuclear Proteins/antagonists & inhibitors/metabolism ; Protein Domains ; *Protein-Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; *RNA-Binding Proteins/antagonists & inhibitors/metabolism ; Transcription Factors/antagonists & inhibitors/metabolism ; }, abstract = {Competitive BET bromodomain inhibitors (BBIs) targeting BET proteins (BRD2, BRD3, BRD4, and BRDT) show promising preclinical activities against brain cancers. However, the BET protein-dependent glioblastoma (GBM)-promoting transcriptional network remains elusive. Here, with mechanistic exploration of a next-generation chemical degrader of BET proteins (dBET6), we reveal a profound and consistent impact of BET proteins on E2F1- dependent transcriptional program in both differentiated GBM cells and brain tumor-initiating cells. dBET6 treatment drastically reduces BET protein genomic occupancy, RNA-Pol2 activity, and permissive chromatin marks. Subsequently, dBET6 represses the proliferation, self-renewal, and tumorigenic ability of GBM cells. Moreover, dBET6-induced degradation of BET proteins exerts superior antiproliferation effects compared to conventional BBIs and overcomes both intrinsic and acquired resistance to BBIs in GBM cells. Our study reveals crucial functions of BET proteins and provides the rationale and therapeutic merits of targeted degradation of BET proteins in GBM.}, } @article {pmid29764998, year = {2018}, author = {Kong, XZ and Mathias, SR and Guadalupe, T and , and Glahn, DC and Franke, B and Crivello, F and Tzourio-Mazoyer, N and Fisher, SE and Thompson, PM and Francks, C}, title = {Mapping cortical brain asymmetry in 17,141 healthy individuals worldwide via the ENIGMA Consortium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5154-E5163}, pmid = {29764998}, issn = {1091-6490}, support = {R01 AA013892/AA/NIAAA NIH HHS/United States ; PL1 DA024859/DA/NIDA NIH HHS/United States ; R01 MH115357/MH/NIMH NIH HHS/United States ; R01 MH086654/MH/NIMH NIH HHS/United States ; P20 DA022539/DA/NIDA NIH HHS/United States ; HHSN271200800009C/DA/NIDA NIH HHS/United States ; R01 EB005846/EB/NIBIB NIH HHS/United States ; T32 DA022975/DA/NIDA NIH HHS/United States ; R01 DA020726/DA/NIDA NIH HHS/United States ; P20 RR021938/RR/NCRR NIH HHS/United States ; R01 MH096773/MH/NIMH NIH HHS/United States ; R01 MH085734/MH/NIMH NIH HHS/United States ; R56 MH086654/MH/NIMH NIH HHS/United States ; RC1 MH089257/MH/NIMH NIH HHS/United States ; U24 RR021992/RR/NCRR NIH HHS/United States ; K99 AA025401/AA/NIAAA NIH HHS/United States ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; R01 DA015179/DA/NIDA NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; R01 DA014100/DA/NIDA NIH HHS/United States ; R01 EB006841/EB/NIBIB NIH HHS/United States ; R01 MH116147/MH/NIMH NIH HHS/United States ; R00 MH091238/MH/NIMH NIH HHS/United States ; P50 DA016556/DA/NIDA NIH HHS/United States ; UL1 DE019586/DE/NIDCR NIH HHS/United States ; P20 GM103472/GM/NIGMS NIH HHS/United States ; G0500092//Medical Research Council/United Kingdom ; R01 MH094524/MH/NIMH NIH HHS/United States ; U54 EB020403/EB/NIBIB NIH HHS/United States ; R01 MH099064/MH/NIMH NIH HHS/United States ; R01 EB000840/EB/NIBIB NIH HHS/United States ; MR/K026992/1//Medical Research Council/United Kingdom ; 500236/Z/11/Z//Wellcome Trust/United Kingdom ; R01 DA018307/DA/NIDA NIH HHS/United States ; K08 MH068540/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cerebral Cortex/*diagnostic imaging ; Child ; Child, Preschool ; Databases, Factual/statistics & numerical data ; Female ; Humans ; Infant ; Male ; Middle Aged ; Neuroimaging/*methods ; Young Adult ; }, abstract = {Hemispheric asymmetry is a cardinal feature of human brain organization. Altered brain asymmetry has also been linked to some cognitive and neuropsychiatric disorders. Here, the ENIGMA (Enhancing NeuroImaging Genetics through Meta-Analysis) Consortium presents the largest-ever analysis of cerebral cortical asymmetry and its variability across individuals. Cortical thickness and surface area were assessed in MRI scans of 17,141 healthy individuals from 99 datasets worldwide. Results revealed widespread asymmetries at both hemispheric and regional levels, with a generally thicker cortex but smaller surface area in the left hemisphere relative to the right. Regionally, asymmetries of cortical thickness and/or surface area were found in the inferior frontal gyrus, transverse temporal gyrus, parahippocampal gyrus, and entorhinal cortex. These regions are involved in lateralized functions, including language and visuospatial processing. In addition to population-level asymmetries, variability in brain asymmetry was related to sex, age, and intracranial volume. Interestingly, we did not find significant associations between asymmetries and handedness. Finally, with two independent pedigree datasets (n = 1,443 and 1,113, respectively), we found several asymmetries showing significant, replicable heritability. The structural asymmetries identified and their variabilities and heritability provide a reference resource for future studies on the genetic basis of brain asymmetry and altered laterality in cognitive, neurological, and psychiatric disorders.}, } @article {pmid29764997, year = {2018}, author = {Lundberg, DS and Teixeira, PJPL}, title = {Root-exuded coumarin shapes the root microbiome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5629-5631}, pmid = {29764997}, issn = {1091-6490}, mesh = {*Coumarins ; *Microbiota ; Plant Roots ; }, } @article {pmid29764690, year = {2018}, author = {Patel, BA and Jashashvili, T and Bui, SH and Carlson, KJ and Griffin, NL and Wallace, IJ and Orr, CM and Susman, RL}, title = {Inter-ray variation in metatarsal strength properties in humans and African apes: Implications for inferring bipedal biomechanics in the Olduvai Hominid 8 foot.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {147-165}, doi = {10.1016/j.jhevol.2018.02.013}, pmid = {29764690}, issn = {1095-8606}, abstract = {When measured as a ratio of mean midshaft diameter to bone length, the OH 8 fossil hominin foot exhibits a metatarsal (Mt) robusticity pattern of 1 > 5 > 3 > 4 > 2, which differs from the widely perceived "common" modern human pattern (1 > 5 > 4 > 3 > 2); African apes generally exhibit a third pattern (1 > 2 > 3 > 4 > 5). Largely because of the relative ranking of Mt2 and Mt5, OH 8 metatarsals structurally resemble the pattern exhibited by bipedal humans more than the pattern of quadrupedal and climbing African apes. Considering only these three phenotypes, however, discounts the potentially important functional implications of variation in modern human (and African ape) metatarsal robusticity patterns, suggesting that they are not useful for interpreting the specific biomechanics of a bipedal gait in fossils (i.e., whether it was modern human-like or not). Using computed tomography scans to quantify metatarsal midshaft cross-sectional geometry in a large sample of Homo (n=130), Gorilla (n=44) and Pan (n=80), we documented greater variation in metatarsal robusticity patterns than previously recognized in all three groups. While apes consistently show a 1 > 2 > 3 > 4 > 5 pattern in our larger sample, there does not appear to be a similarly precise single "common" human pattern. Rather, human metatarsals converge towards a 1 > 4/5 > 2/3 pattern, where metatarsals 4 and 5, and metatarsals 2 and 3, often "flip" positions relative to each other depending on the variable examined. After reassessing what a "common" human pattern could be based on a larger sample, the previously described OH 8 pattern of 1 > 5 > 3 > 4 > 2 is only observed in some humans (<6%) and almost never in apes (<0.5%). Although this suggests an overall greater similarity to (some) humans than to any ape in loading of the foot, the relatively rare frequency of these humans in our sample underscores potential differences in loading experienced by the medial and lateral columns of the OH 8 foot compared to modern humans.}, } @article {pmid29764688, year = {2018}, author = {Bertelsmeier, C and Keller, L}, title = {Bridgehead Effects and Role of Adaptive Evolution in Invasive Populations.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {527-534}, doi = {10.1016/j.tree.2018.04.014}, pmid = {29764688}, issn = {1872-8383}, abstract = {Biological invasions are a major threat to biodiversity, agriculture, and human health. Invasive populations can be the source of additional new introductions, leading to a self-accelerating process whereby invasion begets invasion. This phenomenon, coined bridgehead effect, has been proposed to stem from the evolution of higher invasiveness in a primary introduced population. There is, however, no conclusive evidence that the success of bridgehead populations stems from the evolution of increased invasiveness. Instead, we argue that a high frequency of secondary introductions can be explained by increased abundance in the bridgehead region or the topology of human transport networks. We outline the type of evidence and experiments that are needed to demonstrate adaptive evolution and higher invasion success of introduced populations.}, } @article {pmid29764512, year = {2018}, author = {Widowati, EW and Bamberg-Lemper, S and Becker, W}, title = {Mutational analysis of two residues in the DYRK homology box of the protein kinase DYRK1A.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {297}, pmid = {29764512}, issn = {1756-0500}, mesh = {Animals ; HeLa Cells ; Humans ; Mutation/*genetics ; Phosphorylation ; Protein-Serine-Threonine Kinases/*genetics ; Protein-Tyrosine Kinases/*genetics ; }, abstract = {OBJECTIVE: Dual specificity tyrosine phosphorylation-regulated kinases (DYRK) contain a characteristic sequence motif (DYRK homology box, DH box) that is located N-terminal of the catalytic domain and supports the autophosphorylation of a conserved tyrosine during maturation of the catalytic domain. Two missense mutations in the DH box of human DYRK1B were recently identified as causative of a rare familiar form of metabolic syndrome. We have recently shown that these amino acid exchanges impair maturation of the kinase domain. Here we report the characterization of DYRK1A point mutants (D138P, K150C) that correspond to the pathogenic DYRK1B variants (H90P, R102C).

RESULTS: When expressed in HeLa cells, DYRK1A-D138P and K150C showed no significant difference from wild type DYRK1A regarding the activating tyrosine autophosphorylation or catalytic activity towards exogenous substrates. However, both DYRK1A variants were underphosphorylated on tyrosine when expressed in a bacterial cell free in vitro translation system. These results suggest that D138 and K150 participate in the maturation of the catalytic domain of DYRK1A albeit the mutation of these residues is compensated under physiological conditions.}, } @article {pmid29764503, year = {2018}, author = {Yadav, NS and Sharma, S and Chaudhary, DK and Panthi, P and Pokhrel, P and Shrestha, A and Mandal, PK}, title = {Bacteriological profile of neonatal sepsis and antibiotic susceptibility pattern of isolates admitted at Kanti Children's Hospital, Kathmandu, Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {301}, pmid = {29764503}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*pharmacology ; *Drug Resistance, Bacterial ; Female ; *Gram-Negative Bacterial Infections/blood/epidemiology/microbiology ; *Gram-Positive Bacterial Infections/blood/epidemiology/microbiology ; Humans ; Infant, Newborn ; Klebsiella/drug effects/*isolation & purification ; Male ; Microbial Sensitivity Tests ; *Neonatal Sepsis/blood/epidemiology/microbiology ; Nepal/epidemiology ; Staphylococcus aureus/drug effects/*isolation & purification ; }, abstract = {OBJECTIVE: Neonatal sepsis is a major cause of morbidity and mortality of newborns (< 1 month of age). Septicemia and drug resistance is a predominant issue for neonatal death in Nepal. This study is intended to find bacteriological profile of neonatal sepsis and antibiotic susceptibility pattern of the isolates from neonates at Kanti Children's Hospital, Kathmandu, Nepal.

RESULTS: Out of 350 suspected cases of neonatal sepsis, 59 (16.9%) cases showed positive blood culture. The prevalent of positive blood culture with different neonatal risk factors (sex, age, birth weight, gestational age, and delivery mode) showed highest positive bacterial growth in male (52.3%); 3 or above 3 days age (71.2%); low birth weight (62.7%); preterm gestational age (31.4%); and caesarean delivery mode (63.3%). Among positive cases, the bacteriological profile was found highest for Staphylococcus aureus (35.6%) followed by Klebsiella pneumoniae (15.3%). The most sensitive and resistive antibiotics among Gram-positive isolates were gentamicin (93%) and ampicillin (78%), respectively. Meropenem and imipenem showed highest 100% effective and cefotaxime was least (28%) sensitive among Gram-negative isolates. This concludes broad ranges of bacteria are associated with neonatal sepsis and revealed variation in antibiotic susceptibility pattern among bacterial isolates.}, } @article {pmid29764499, year = {2018}, author = {Crusell, MKW and Hansen, TH and Nielsen, T and Allin, KH and Rühlemann, MC and Damm, P and Vestergaard, H and Rørbye, C and Jørgensen, NR and Christiansen, OB and Heinsen, FA and Franke, A and Hansen, T and Lauenborg, J and Pedersen, O}, title = {Gestational diabetes is associated with change in the gut microbiota composition in third trimester of pregnancy and postpartum.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {89}, pmid = {29764499}, issn = {2049-2618}, support = {1076001001//Augustinus Fonden (DK)/International ; 10-001605//Aase og Ejnar Danielsens Fond/International ; }, mesh = {Actinobacteria/genetics/isolation & purification ; Adult ; Blood Glucose ; Body Mass Index ; Clostridium/genetics/isolation & purification ; Desulfovibrio/genetics/isolation & purification ; Diabetes, Gestational/*microbiology ; Dysbiosis/*microbiology ; Faecalibacterium/genetics/isolation & purification ; Female ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Glucose/metabolism ; Humans ; Postpartum Period/*blood ; Pregnancy ; Pregnancy Trimester, Third/*blood ; RNA, Ribosomal, 16S/genetics ; Surveys and Questionnaires ; }, abstract = {BACKGROUND: Imbalances of gut microbiota composition are linked to a range of metabolic perturbations. In the present study, we examined the gut microbiota of women with gestational diabetes mellitus (GDM) and normoglycaemic pregnant women in late pregnancy and about 8 months postpartum.

METHODS: Gut microbiota profiles of women with GDM (n = 50) and healthy (n = 157) pregnant women in the third trimester and 8 months postpartum were assessed by 16S rRNA gene amplicon sequencing of the V1-V2 region. Insulin and glucose homeostasis were evaluated by a 75 g 2-h oral glucose tolerance test during and after pregnancy.

RESULTS: Gut microbiota of women with GDM was aberrant at multiple levels, including phylum and genus levels, compared with normoglycaemic pregnant women. Actinobacteria at phylum level and Collinsella, Rothia and Desulfovibrio at genus level had a higher abundance in the GDM cohort. Difference in abundance of 17 species-level operational taxonomic units (OTUs) during pregnancy was associated with GDM. After adjustment for pre-pregnancy body mass index (BMI), 5 of the 17 OTUs showed differential abundance in the GDM cohort compared with the normoglycaemic pregnant women with enrichment of species annotated to Faecalibacterium and Anaerotruncus and depletion of species annotated to Clostridium (sensu stricto) and to Veillonella. OTUs assigned to Akkermansia were associated with lower insulin sensitivity while Christensenella OTUs were associated with higher fasting plasma glucose concentration. OTU richness and Shannon index decreased from late pregnancy to postpartum regardless of metabolic status. About 8 months after delivery, the microbiota of women with previous GDM was still characterised by an aberrant composition. Thirteen OTUs were differentially abundant in women with previous GDM compared with women with previous normoglycaemic pregnancy.

CONCLUSION: GDM diagnosed in the third trimester of pregnancy is associated with a disrupted gut microbiota composition compared with normoglycaemic pregnant women, and 8 months after pregnancy, differences in the gut microbiota signatures are still detectable. The gut microbiota composition of women with GDM, both during and after pregnancy, resembles the aberrant microbiota composition reported in non-pregnant individuals with type 2 diabetes and associated intermediary metabolic traits.}, } @article {pmid29764489, year = {2018}, author = {Russell, PH and Vestal, B and Shi, W and Rudra, PD and Dowell, R and Radcliffe, R and Saba, L and Kechris, K}, title = {miR-MaGiC improves quantification accuracy for small RNA-seq.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {296}, pmid = {29764489}, issn = {1756-0500}, support = {T15LM009451//U.S. National Library of Medicine/ ; T15 LM009451/LM/NLM NIH HHS/United States ; R01AA021131//National Institute on Alcohol Abuse and Alcoholism/ ; R01AA016957//National Institute on Alcohol Abuse and Alcoholism/ ; R01 AA016957/AA/NIAAA NIH HHS/United States ; R01 AA021131/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; High-Throughput Nucleotide Sequencing/*methods ; Mice ; MicroRNAs/*metabolism ; Sequence Analysis, RNA/*methods ; }, abstract = {OBJECTIVE: Many tools have been developed to profile microRNA (miRNA) expression from small RNA-seq data. These tools must contend with several issues: the small size of miRNAs, the small number of unique miRNAs, the fact that similar miRNAs can be transcribed from multiple loci, and the presence of miRNA isoforms known as isomiRs. Methods failing to address these issues can return misleading information. We propose a novel quantification method designed to address these concerns.

RESULTS: We present miR-MaGiC, a novel miRNA quantification method, implemented as a cross-platform tool in Java. miR-MaGiC performs stringent mapping to a core region of each miRNA and defines a meaningful set of target miRNA sequences by collapsing the miRNA space to "functional groups". We hypothesize that these two features, mapping stringency and collapsing, provide more optimal quantification to a more meaningful unit (i.e., miRNA family). We test miR-MaGiC and several published methods on 210 small RNA-seq libraries, evaluating each method's ability to accurately reflect global miRNA expression profiles. We define accuracy as total counts close to the total number of input reads originating from miRNAs. We find that miR-MaGiC, which incorporates both stringency and collapsing, provides the most accurate counts.}, } @article {pmid29764479, year = {2018}, author = {Iskandar, K and Patria, SY and Huriyati, E and Luglio, HF and Julia, M and Susilowati, R}, title = {Effect of FTO rs9939609 variant on insulin resistance in obese female adolescents.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {300}, pmid = {29764479}, issn = {1756-0500}, mesh = {Adolescent ; Alpha-Ketoglutarate-Dependent Dioxygenase FTO/*genetics ; Child ; Female ; Humans ; Indonesia ; Insulin Resistance/*genetics ; Pediatric Obesity/*genetics ; Polymorphism, Genetic ; }, abstract = {OBJECTIVES: FTO rs9939609 variant has been shown to be associated with insulin resistance in Caucasian children. However, studies in Asia show inconsistent findings. We investigated the association between FTO rs9939609 polymorphisms and insulin resistance in obese female adolescents in Indonesia, a genetically distinct group within Asia.

RESULTS: A total of 78 obese female adolescents participated in this study. The risk allele (A) frequency of FTO rs9939609 variant in Indonesian obese female adolescence was 44.2%. The frequency of insulin resistance was higher in the subjects with AA (54.6%) or AT (59.6%) than the subject with TT genotype (50%), but did not statistically different (p = 0.81 and p = 0.47, respectively). The insulin resistance rate was also higher in the risk allele (A) than the non-risk allele (T) subjects (0.58 vs. 0.55), but did not statistically different (p = 0.75). There was no association between FTO rs9939609 variant and body mass index, fasting glucose level, fasting insulin level, homeostatic model assessment of insulin resistance, and waist circumference (p > 0.05). In conclusion, FTO rs9939609 variant may not be associated with insulin resistance in Indonesian obese female adolescents. A multicenter study with a larger sample size is needed to clarify these findings.}, } @article {pmid29764477, year = {2018}, author = {Wagnew, F and Eshetie, S and Alebel, A and Dessie, G and Tesema, C and Abajobir, AA}, title = {Meta-analysis of the prevalence of tuberculosis in diabetic patients and its association with cigarette smoking in African and Asian countries.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {298}, pmid = {29764477}, issn = {1756-0500}, mesh = {Africa/epidemiology ; Asia/epidemiology ; Cigarette Smoking/*epidemiology ; *Comorbidity ; Diabetes Mellitus/*epidemiology ; Humans ; Tuberculosis/*epidemiology ; }, abstract = {OBJECTIVE: This systematic review and meta-analysis was undertaken to estimate the prevalence of tuberculosis in diabetic patients and to determine the effect of cigarette smoking.

RESULTS: A total of 15 studies was included in the meta-analysis. The pooled overall prevalence of tuberculosis in diabetes was 4.72% (95% CI 3.62-5.83%). In sub-group analyses, the prevalence was 5.13% (95% CI 4.34-5.92%) in Africa, followed by 4.16% (95% CI 2.9-5.4%) in Asia. The odd ratio of tuberculosis among diabetes patients was 7.6 (95% CI 1.46-39) in cigarette smokers as compared to nonsmokers. Publication bias was detected based on graphic asymmetry of fun-nel plots, Begg's and Egger's tests (p < 0.05). Tuberculosis is a common co-morbidity in diabetic patients. Tuberculosis-diabetes co-morbidity is significantly higher in cigarette smokers.}, } @article {pmid29764476, year = {2018}, author = {Mehmood, A and Zia, N and Hoe, C and Kobusingye, O and Ssenyojo, H and Hyder, AA}, title = {Traumatic brain injury in Uganda: exploring the use of a hospital based registry for measuring burden and outcomes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {299}, pmid = {29764476}, issn = {1756-0500}, support = {R21 NS085094/NS/NINDS NIH HHS/United States ; R21NS085094//Fogarty International Center/ ; }, mesh = {Brain Injuries, Traumatic/*epidemiology/therapy ; *Cost of Illness ; Hospitals/*statistics & numerical data ; Humans ; Outcome Assessment (Health Care)/*statistics & numerical data ; Registries/*statistics & numerical data ; Uganda/epidemiology ; }, abstract = {OBJECTIVE: Lack of data on traumatic brain injuries (TBI) hinders the appreciation of the true magnitude of the TBI burden. This paper describes a scientific approach for hospital based systematic data collection in a low-income country. The registry is based on the evaluation framework for injury surveillance systems which comprises a four-step approach: (1) identifying characteristics that assess a surveillance system, (2) review of the identified variables based on adopted specific, measurable, assignable, realistic, and time-related criteria, (3) assessment of the proposed variables and system characteristics by an expert panel, and (4) development and application of a rating system.

RESULTS: The electronic hospital-based TBI registry is designed through a collaborative approach to capture comprehensive, yet context specific, information on each TBI case, from the time of injury until death or discharge from the hospital. It includes patients' demographics, pre-hospital and hospital assessment and care, TBI causes, injury severity, and patient outcomes. The registry in Uganda will open the opportunity to replicate the process in other similar context and contribute to a better understanding of TBI in these settings, and feed into the global agenda of reducing deaths and disabilities from TBI in low-and middle-income countries.}, } @article {pmid29764437, year = {2018}, author = {Garay, J and Számadó, S and Varga, Z and Szathmáry, E}, title = {Caring for parents: an evolutionary rationale.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {53}, pmid = {29764437}, issn = {1741-7007}, abstract = {BACKGROUND: The evolutionary roots of human moral behavior are a key precondition to understanding human nature. Investigations usually start with a social dilemma and end up with a norm that can provide some insight into the origin of morality. We take the opposite direction by investigating whether the cultural norm that promotes helping parents and which is respected in different variants across cultures and is codified in several religions can spread through Darwinian competition.

RESULTS: We show with a novel demographic model that the biological rule "During your reproductive period, give some of your resources to your post-fertile parents" will spread even if the cost of support given to post-fertile grandmothers considerably decreases the demographic parameters of fertile parents but radically increases the survival rate of grandchildren. The teaching of vital cultural content is likely to have been critical in making grandparental service valuable. We name this the Fifth Rule, after the Fifth Commandment that codifies such behaviors in Christianity.

CONCLUSIONS: Selection for such behavior may have produced an innate moral tendency to honor parents even in situations, such as those experienced today, when the quantitative conditions would not necessarily favor the maintenance of this trait.}, } @article {pmid29764421, year = {2018}, author = {Zhou, X and Zheng, J and Ivan, FX and Yin, R and Ranganathan, S and Chow, VTK and Kwoh, CK}, title = {Computational analysis of the receptor binding specificity of novel influenza A/H7N9 viruses.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {88}, pmid = {29764421}, issn = {1471-2164}, mesh = {Animals ; Avian Proteins/metabolism ; Birds ; Computational Biology/*methods ; Hemagglutinin Glycoproteins, Influenza Virus/*chemistry/*genetics/metabolism ; Host Microbial Interactions ; Humans ; Influenza A Virus, H7N9 Subtype/classification/genetics/*physiology ; Molecular Docking Simulation ; Molecular Dynamics Simulation ; *Mutation ; Phylogeny ; Protein Binding ; Sequence Analysis, RNA/methods ; Viral Proteins/chemistry/genetics ; }, abstract = {BACKGROUND: Influenza viruses are undergoing continuous and rapid evolution. The fatal influenza A/H7N9 has drawn attention since the first wave of infections in March 2013, and raised more grave concerns with its increased potential to spread among humans. Experimental studies have revealed several host and virulence markers, indicating differential host binding preferences which can help estimate the potential of causing a pandemic. Here we systematically investigate the sequence pattern and structural characteristics of novel influenza A/H7N9 using computational approaches.

RESULTS: The sequence analysis highlighted mutations in protein functional domains of influenza viruses. Molecular docking and molecular dynamics simulation revealed that the hemagglutinin (HA) of A/Taiwan/1/2017(H7N9) strain enhanced the binding with both avian and human receptor analogs, compared with the previous A/Shanghai/02/2013(H7N9) strain. The Molecular Mechanics - Poisson Boltzmann Surface Area (MM-PBSA) calculation revealed the change of residue-ligand interaction energy and detected the residues with conspicuous binding preference.

CONCLUSION: The results are novel and specific to the emerging influenza A/Taiwan/1/2017(H7N9) strain compared with A/Shanghai/02/2013(H7N9). Its enhanced ability to bind human receptor analogs, which are abundant in the human upper respiratory tract, may be responsible for the recent outbreak. Residues showing binding preference were detected, which could facilitate monitoring the circulating influenza viruses.}, } @article {pmid29764394, year = {2018}, author = {Chen, W and Zhang, X and Li, J and Huang, S and Xiang, S and Hu, X and Liu, C}, title = {Comprehensive analysis of coding-lncRNA gene co-expression network uncovers conserved functional lncRNAs in zebrafish.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {112}, pmid = {29764394}, issn = {1471-2164}, mesh = {Animals ; Base Sequence ; Computational Biology/methods ; Conserved Sequence ; Databases, Genetic ; Gene Ontology ; *Gene Regulatory Networks ; RNA, Long Noncoding/*genetics ; Sequence Analysis, RNA/*methods ; Zebrafish/*genetics ; Zebrafish Proteins/genetics ; }, abstract = {BACKGROUND: Zebrafish is a full-developed model system for studying development processes and human disease. Recent studies of deep sequencing had discovered a large number of long non-coding RNAs (lncRNAs) in zebrafish. However, only few of them had been functionally characterized. Therefore, how to take advantage of the mature zebrafish system to deeply investigate the lncRNAs' function and conservation is really intriguing.

RESULTS: We systematically collected and analyzed a series of zebrafish RNA-seq data, then combined them with resources from known database and literatures. As a result, we obtained by far the most complete dataset of zebrafish lncRNAs, containing 13,604 lncRNA genes (21,128 transcripts) in total. Based on that, a co-expression network upon zebrafish coding and lncRNA genes was constructed and analyzed, and used to predict the Gene Ontology (GO) and the KEGG annotation of lncRNA. Meanwhile, we made a conservation analysis on zebrafish lncRNA, identifying 1828 conserved zebrafish lncRNA genes (1890 transcripts) that have their putative mammalian orthologs. We also found that zebrafish lncRNAs play important roles in regulation of the development and function of nervous system; these conserved lncRNAs present a significant sequential and functional conservation, with their mammalian counterparts.

CONCLUSIONS: By integrative data analysis and construction of coding-lncRNA gene co-expression network, we gained the most comprehensive dataset of zebrafish lncRNAs up to present, as well as their systematic annotations and comprehensive analyses on function and conservation. Our study provides a reliable zebrafish-based platform to deeply explore lncRNA function and mechanism, as well as the lncRNA commonality between zebrafish and human.}, } @article {pmid29764390, year = {2018}, author = {Chow, CN and Chiang-Hsieh, YF and Chien, CH and Zheng, HQ and Lee, TY and Wu, NY and Tseng, KC and Hou, PF and Chang, WC}, title = {Delineation of condition specific Cis- and Trans-acting elements in plant promoters under various Endo- and exogenous stimuli.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {85}, pmid = {29764390}, issn = {1471-2164}, mesh = {Abscisic Acid/pharmacology ; Arabidopsis/drug effects/genetics/*growth & development ; Arabidopsis Proteins/genetics ; Computational Biology/*methods ; Gene Expression Profiling ; Gene Expression Regulation, Developmental/drug effects ; Gene Expression Regulation, Plant/drug effects ; *Promoter Regions, Genetic ; Stress, Physiological ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: Transcription factors (TFs) play essential roles during plant development and response to environmental stresses. However, the relationships among transcription factors, cis-acting elements and target gene expression under endo- and exogenous stimuli have not been systematically characterized.

RESULTS: Here, we developed a series of bioinformatics analysis methods to infer transcriptional regulation by using numerous gene expression data from abiotic stresses and hormones treatments. After filtering the expression profiles of TF-encoding genes, 291 condition specific transcription factors (CsTFs) were obtained. Differentially expressed genes were then classified into various co-expressed gene groups based on each CsTFs. In the case studies of heat stress and ABA treatment, several known and novel cis-acting elements were identified following our bioinformatics approach. Significantly, a palindromic sequence of heat-responsive elements is recognized, and also obtained from a 3D protein structure of heat-shock protein-DNA complex. Notably, overrepresented 3- and 4-mer motifs in an enriched 8-mer motif could be a core cis-element for a CsTF. In addition, the results suggest DNA binding preferences of the same CsTFs are different according to various conditions.

CONCLUSIONS: The overall results illustrate this study may be useful in identifying condition specific cis- and trans- regulatory elements and facilitate our understanding of the relationships among TFs, cis-acting elements and target gene expression.}, } @article {pmid29764387, year = {2018}, author = {Liu, L and Ren, S and Guo, J and Wang, Q and Zhang, X and Liao, P and Li, S and Sunkar, R and Zheng, Y}, title = {Genome-wide identification and comprehensive analysis of microRNAs and phased small interfering RNAs in watermelon.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {111}, pmid = {29764387}, issn = {1471-2164}, mesh = {Citrullus/*genetics ; Computational Biology ; Flowers/genetics ; Fruit/genetics ; Gene Expression Regulation, Plant ; Genome, Plant ; High-Throughput Nucleotide Sequencing/*methods ; MicroRNAs/*genetics ; Plant Leaves/genetics ; RNA, Plant/genetics ; RNA, Small Interfering/*genetics ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) are a class of endogenous small non-coding RNAs involved in the post-transcriptional gene regulation and play a critical role in plant growth, development and stress responses. Watermelon (Citrullus lanatus L.) is one of the important agricultural crops worldwide. However, the watermelon miRNAs and phasiRNAs and their functions are not well explored.

RESULTS: Here we carried out computational and experimental analysis of miRNAs and phased small interfering RNAs (phasiRNAs) in watermelon by analyzing 14 small RNA profiles from roots, leaves, androecium, petals, and fruits, and one published small RNA profile of mixed tissues. To identify the targets of miRNAs and phasiRNAs, we generated a degradome profile for watermelon leaf which is analyzed using the SeqTar algorithm. We identified 97 conserved pre-miRNAs, of which 58 have not been reported previously and 348 conserved mature miRNAs without precursors. We also found 9 novel pre-miRNAs encoding 18 mature miRNAs. One hundred and one 21 nucleotide (nt) PHAS loci, and two hundred and forty one 24 nt PHAS loci were also identified. We identified 127 conserved targets of the conserved miRNAs and TAS3-derived tasiRNAs by analyzing a degradome profile of watermelon leaf.

CONCLUSIONS: The presented results provide a comprehensive view of small regulatory RNAs and their targets in watermelon.}, } @article {pmid29764379, year = {2018}, author = {Choi, Y and Liu, TT and Pankratz, DG and Colby, TV and Barth, NM and Lynch, DA and Walsh, PS and Raghu, G and Kennedy, GC and Huang, J}, title = {Identification of usual interstitial pneumonia pattern using RNA-Seq and machine learning: challenges and solutions.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {101}, pmid = {29764379}, issn = {1471-2164}, mesh = {Area Under Curve ; Biopsy ; Computational Biology/methods ; Computer Simulation ; Diagnosis, Differential ; Genetic Predisposition to Disease ; Humans ; Idiopathic Interstitial Pneumonias/*diagnosis/*genetics ; Idiopathic Pulmonary Fibrosis/*diagnosis/*genetics ; Logistic Models ; Machine Learning ; Prospective Studies ; ROC Curve ; Sensitivity and Specificity ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: We developed a classifier using RNA sequencing data that identifies the usual interstitial pneumonia (UIP) pattern for the diagnosis of idiopathic pulmonary fibrosis. We addressed significant challenges, including limited sample size, biological and technical sample heterogeneity, and reagent and assay batch effects.

RESULTS: We identified inter- and intra-patient heterogeneity, particularly within the non-UIP group. The models classified UIP on transbronchial biopsy samples with a receiver-operating characteristic area under the curve of ~ 0.9 in cross-validation. Using in silico mixed samples in training, we prospectively defined a decision boundary to optimize specificity at ≥85%. The penalized logistic regression model showed greater reproducibility across technical replicates and was chosen as the final model. The final model showed sensitivity of 70% and specificity of 88% in the test set.

CONCLUSIONS: We demonstrated that the suggested methodologies appropriately addressed challenges of the sample size, disease heterogeneity and technical batch effects and developed a highly accurate and robust classifier leveraging RNA sequencing for the classification of UIP.}, } @article {pmid29764378, year = {2018}, author = {Kim, JS and Senol Cali, D and Xin, H and Lee, D and Ghose, S and Alser, M and Hassan, H and Ergin, O and Alkan, C and Mutlu, O}, title = {GRIM-Filter: Fast seed location filtering in DNA read mapping using processing-in-memory technologies.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {89}, pmid = {29764378}, issn = {1471-2164}, support = {R01 HG006004/HG/NHGRI NIH HHS/United States ; }, mesh = {Algorithms ; Databases, Genetic ; Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Sequence Analysis, DNA/*methods ; Software ; }, abstract = {BACKGROUND: Seed location filtering is critical in DNA read mapping, a process where billions of DNA fragments (reads) sampled from a donor are mapped onto a reference genome to identify genomic variants of the donor. State-of-the-art read mappers 1) quickly generate possible mapping locations for seeds (i.e., smaller segments) within each read, 2) extract reference sequences at each of the mapping locations, and 3) check similarity between each read and its associated reference sequences with a computationally-expensive algorithm (i.e., sequence alignment) to determine the origin of the read. A seed location filter comes into play before alignment, discarding seed locations that alignment would deem a poor match. The ideal seed location filter would discard all poor match locations prior to alignment such that there is no wasted computation on unnecessary alignments.

RESULTS: We propose a novel seed location filtering algorithm, GRIM-Filter, optimized to exploit 3D-stacked memory systems that integrate computation within a logic layer stacked under memory layers, to perform processing-in-memory (PIM). GRIM-Filter quickly filters seed locations by 1) introducing a new representation of coarse-grained segments of the reference genome, and 2) using massively-parallel in-memory operations to identify read presence within each coarse-grained segment. Our evaluations show that for a sequence alignment error tolerance of 0.05, GRIM-Filter 1) reduces the false negative rate of filtering by 5.59x-6.41x, and 2) provides an end-to-end read mapper speedup of 1.81x-3.65x, compared to a state-of-the-art read mapper employing the best previous seed location filtering algorithm.

CONCLUSION: GRIM-Filter exploits 3D-stacked memory, which enables the efficient use of processing-in-memory, to overcome the memory bandwidth bottleneck in seed location filtering. We show that GRIM-Filter significantly improves the performance of a state-of-the-art read mapper. GRIM-Filter is a universal seed location filter that can be applied to any read mapper. We hope that our results provide inspiration for new works to design other bioinformatics algorithms that take advantage of emerging technologies and new processing paradigms, such as processing-in-memory using 3D-stacked memory devices.}, } @article {pmid29764377, year = {2018}, author = {Tao, W and Chen, J and Tan, D and Yang, J and Sun, L and Wei, J and Conte, MA and Kocher, TD and Wang, D}, title = {Transcriptome display during tilapia sex determination and differentiation as revealed by RNA-Seq analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {363}, pmid = {29764377}, issn = {1471-2164}, support = {31502147//National Natural Science Foundation of China/ ; 31630082//National Natural Science Foundation of China/ ; 31572609//National Natural Science Foundation of China/ ; 20130182130003//Specialized Research Fund for the Doctoral Program of Higher Education of China/ ; cstc2014jcyjA80003//Natural Science Foundation Project of Chongqing/ ; cstc2014jcyjA8000//Natural Science Foundation Project of Chongqing/ ; XDJK2016B011//Fundamental Research Funds for the Central Universities (Ministry of Education of China)/ ; XDJK2017B007//Fundamental Research Funds for the Central Universities (Ministry of Education of China)/ ; XDJK2016A003//Fundamental Research Funds for the Central Universities (Ministry of Education of China)/ ; }, mesh = {Animals ; Apoptosis/genetics ; Female ; Fish Proteins/genetics/metabolism ; *Gene Expression Profiling ; Gene Regulatory Networks ; Male ; Ovary/cytology/growth & development ; *Sequence Analysis, RNA ; Sex Determination Processes/*genetics ; Sex Differentiation/*genetics ; Testis/cytology/growth & development ; Tilapia/*genetics/growth & development ; }, abstract = {BACKGROUND: The factors determining sex in teleosts are diverse. Great efforts have been made to characterize the underlying genetic network in various species. However, only seven master sex-determining genes have been identified in teleosts. While the function of a few genes involved in sex determination and differentiation has been studied, we are far from fully understanding how genes interact to coordinate in this process.

RESULTS: To enable systematic insights into fish sexual differentiation, we generated a dynamic co-expression network from tilapia gonadal transcriptomes at 5, 20, 30, 40, 90, and 180 dah (days after hatching), plus 45 and 90 dat (days after treatment) and linked gene expression profiles to both development and sexual differentiation. Transcriptomic profiles of female and male gonads at 5 and 20 dah exhibited high similarities except for a small number of genes that were involved in sex determination, while drastic changes were observed from 90 to 180 dah, with a group of differently expressed genes which were involved in gonadal differentiation and gametogenesis. Weighted gene correlation network analysis identified changes in the expression of Borealin, Gtsf1, tesk1, Zar1, Cdn15, and Rpl that were correlated with the expression of genes previously known to be involved in sex differentiation, such as Foxl2, Cyp19a1a, Gsdf, Dmrt1, and Amh.

CONCLUSIONS: Global gonadal gene expression kinetics during sex determination and differentiation have been extensively profiled in tilapia. These findings provide insights into the genetic framework underlying sex determination and sexual differentiation, and expand our current understanding of developmental pathways during teleost sex determination.}, } @article {pmid29764375, year = {2018}, author = {Chou, CH and Huang, HY and Huang, WC and Hsu, SD and Hsiao, CD and Liu, CY and Chen, YH and Liu, YC and Huang, WY and Lee, ML and Chen, YC and Huang, HD}, title = {The aquatic animals' transcriptome resource for comparative functional analysis.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {103}, pmid = {29764375}, issn = {1471-2164}, mesh = {Animals ; Aquatic Organisms/*genetics ; Databases, Genetic ; Gene Expression Profiling/*methods ; Gene Regulatory Networks ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/methods ; Molecular Sequence Annotation ; Phylogeny ; Sequence Analysis, RNA/methods ; Software ; }, abstract = {BACKGROUND: Aquatic animals have great economic and ecological importance. Among them, non-model organisms have been studied regarding eco-toxicity, stress biology, and environmental adaptation. Due to recent advances in next-generation sequencing techniques, large amounts of RNA-seq data for aquatic animals are publicly available. However, currently there is no comprehensive resource exist for the analysis, unification, and integration of these datasets. This study utilizes computational approaches to build a new resource of transcriptomic maps for aquatic animals. This aquatic animal transcriptome map database dbATM provides de novo assembly of transcriptome, gene annotation and comparative analysis of more than twenty aquatic organisms without draft genome.

RESULTS: To improve the assembly quality, three computational tools (Trinity, Oases and SOAPdenovo-Trans) were employed to enhance individual transcriptome assembly, and CAP3 and CD-HIT-EST software were then used to merge these three assembled transcriptomes. In addition, functional annotation analysis provides valuable clues to gene characteristics, including full-length transcript coding regions, conserved domains, gene ontology and KEGG pathways. Furthermore, all aquatic animal genes are essential for comparative genomics tasks such as constructing homologous gene groups and blast databases and phylogenetic analysis.

CONCLUSION: In conclusion, we establish a resource for non model organism aquatic animals, which is great economic and ecological importance and provide transcriptomic information including functional annotation and comparative transcriptome analysis. The database is now publically accessible through the URL http://dbATM.mbc.nctu.edu.tw/ .}, } @article {pmid29764374, year = {2018}, author = {Ma, F and Lin, P and Chen, Q and Lu, X and Zhang, YE and Wu, CI}, title = {Direct measurement of pervasive weak repression by microRNAs and their role at the network level.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {362}, pmid = {29764374}, issn = {1471-2164}, mesh = {3' Untranslated Regions/genetics ; *Gene Regulatory Networks ; MicroRNAs/*genetics ; Models, Genetic ; RNA Stability ; Transcription, Genetic ; }, abstract = {BACKGROUND: A gene regulatory network (GRN) comprises many weak links that are often regulated by microRNAs. Since miRNAs rarely repress their target genes by more than 30%, doubts have been expressed about the biological relevance of such weak effects. These doubts raise the possibility of under-estimation as miRNA repression is usually estimated indirectly from equilibrium expression levels.

RESULTS: To measure miRNA repression directly, we inhibited transcript synthesis in Drosophila larvae and collected time-course data on mRNA abundance, the decline of which reflects transcript degradation. The rate of target degradation in the absence of miR310s, a moderately expressed miRNA family, was found to decrease by 5 to 15%. A conventional analysis that does not remove transcript synthesis yields an estimate of 6.5%, within the range of the new estimates. These data permit further examinations of the repression mechanisms by miRNAs including seed matching types, APA (alternative polyadenylation) sites, effects of other highly-expressed miRNAs and the length of 3'UTR. Our direct measurements suggest the latter two factors have a measurable effect on decay rate.

CONCLUSION: The direct measurement confirms pervasive weak repression by miRNAs, supporting the conclusions based on indirect assays. The confirmation suggests that this weak repression may indeed be miRNAs' main function. In this context, we discuss the recent proposal that weak repression is "cumulatively powerful" in stabilizing GRNs.}, } @article {pmid29764372, year = {2018}, author = {Gostinčar, C and Stajich, JE and Zupančič, J and Zalar, P and Gunde-Cimerman, N}, title = {Genomic evidence for intraspecific hybridization in a clonal and extremely halotolerant yeast.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {364}, pmid = {29764372}, issn = {1471-2164}, support = {MRIC UL//Javna Agencija za Raziskovalno Dejavnost RS/ ; P1-0170//Javna Agencija za Raziskovalno Dejavnost RS/ ; P1-0207//Javna Agencija za Raziskovalno Dejavnost RS/ ; 382228-1/2013//Ministrstvo za Izobraževanje, Znanost in Šport/ ; }, mesh = {Ascomycota/*genetics/*physiology ; Diploidy ; Ecosystem ; Genome, Fungal/genetics ; *Genomics ; *Hybridization, Genetic ; Phylogeny ; }, abstract = {BACKGROUND: The black yeast Hortaea werneckii (Dothideomycetes, Ascomycota) is one of the most extremely halotolerant fungi, capable of growth at NaCl concentrations close to saturation. Although dothideomycetous fungi are typically haploid, the reference H. werneckii strain has a diploid genome consisting of two subgenomes with a high level of heterozygosity.

RESULTS: In order to explain the origin of the H. werneckii diploid genome we here report the genome sequencing of eleven strains isolated from different habitats and geographic locations. Comparison of nine diploid and two haploid strains showed that the reference genome was likely formed by hybridization between two haploids and not by endoreduplication as suggested previously. Results also support additional hybridization events in the evolutionary history of investigated strains, however exchange of genetic material in the species otherwise appears to be rare. Possible links between such unusual reproduction and the extremotolerance of H. werneckii remain to be investigated.

CONCLUSIONS: H. werneckii appears to be able to form persistent haploid as well as diploid strains, is capable of occasional hybridization between relatively heterozygous haploids, but is otherwise limited to clonal reproduction. The reported data and the first identification of haploid H. werneckii strains establish this species as a good model for studying the effects of ploidy and hybridization in an extremotolerant system unperturbed by frequent genetic recombination.}, } @article {pmid29764371, year = {2018}, author = {Zheng, C and Jeong, Y and Turcotte, MG and Sankoff, D}, title = {Resolution effects in reconstructing ancestral genomes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {100}, pmid = {29764371}, issn = {1471-2164}, mesh = {Algorithms ; Animals ; Apocynaceae/*genetics ; Coffea/*genetics ; Evolution, Molecular ; Gene Order ; *Genome, Plant ; Models, Genetic ; Mutation ; Phylogeny ; Synteny ; Vitis/*genetics ; }, abstract = {BACKGROUND: The reconstruction of ancestral genomes must deal with the problem of resolution, necessarily involving a trade-off between trying to identify genomic details and being overwhelmed by noise at higher resolutions.

RESULTS: We use the median reconstruction at the synteny block level, of the ancestral genome of the order Gentianales, based on coffee, Rhazya stricta and grape, to exemplify the effects of resolution (granularity) on comparative genomic analyses.

CONCLUSIONS: We show how decreased resolution blurs the differences between evolving genomes, with respect to rate, mutational process and other characteristics.}, } @article {pmid29764369, year = {2018}, author = {Huang, PJ and Lee, CC and Chiu, LY and Huang, KY and Yeh, YM and Yang, CY and Chiu, CH and Tang, P}, title = {VAReporter: variant reporter for cancer research of massive parallel sequencing.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {86}, pmid = {29764369}, issn = {1471-2164}, mesh = {Algorithms ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Internet ; Molecular Sequence Annotation ; *Mutation ; Neoplasms/*genetics ; Precision Medicine ; Whole Exome Sequencing/*methods ; Workflow ; }, abstract = {BACKGROUND: High throughput sequencing technologies have been an increasingly critical aspect of precision medicine owing to a better identification of disease targets, which contributes to improved health care cost and clinical outcomes. In particular, disease-oriented targeted enrichment sequencing is becoming a widely-accepted application for diagnostic purposes, which can interrogate known diagnostic variants as well as identify novel biomarkers from panels of entire human coding exome or disease-associated genes.

RESULTS: We introduce a workflow named VAReporter to facilitate the management of variant assessment in disease-targeted sequencing, the identification of pathogenic variants, the interpretation of biological effects and the prioritization of clinically actionable targets. State-of-art algorithms that account for mutation phenotypes are used to rank the importance of mutated genes through visual analytic strategies. We established an extensive annotation source by integrating a wide variety of biomedical databases and followed the American College of Medical Genetics and Genomics (ACMG) guidelines for interpretation and reporting of sequence variations.

CONCLUSIONS: In summary, VAReporter is the first web server designed to provide a "one-stop" resource for individual's diagnosis and large-scale cohort studies, and is freely available at http://rnd.cgu.edu.tw/vareporter .}, } @article {pmid29764367, year = {2018}, author = {Wang, W and Zhou, XM and Xiong, HX and Mao, WY and Zhao, P and Sun, MX}, title = {Papain-like and legumain-like proteases in rice: genome-wide identification, comprehensive gene feature characterization and expression analysis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {87}, pmid = {29764367}, issn = {1471-2229}, support = {31400171//the National Natural Science Fund of China/ ; 31600244//the National Natural Science Fund of Chona/ ; }, mesh = {Chromosome Mapping ; Chromosomes, Plant/genetics ; Cysteine Endopeptidases/*genetics/metabolism ; Gene Expression Profiling ; Genes, Plant/*genetics/physiology ; Genome-Wide Association Study ; Oryza/*enzymology/genetics ; Papain/*genetics/metabolism ; Peptide Hydrolases/*genetics/metabolism ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Sequence Alignment ; }, abstract = {BACKGROUND: Papain-like and legumain-like proteases are proteolytic enzymes which play key roles in plant development, senescence and defense. The activities of proteases in both families could be inhibited by a group of small proteins called cystatin. Cystatin family genes have been well characterized both in tobacco and rice, suggesting their potential roles in seed development. However, their potential targets, papain-like and legumain-like proteases, have not been well characterized in plants, especially in rice, a model plant for cereal biology.

RESULTS: Here, 33 papain-like and 5 legumain-like proteases have been identified in rice genome, respectively. Gene structure, distribution in rice chromosome, and evolutionary relationship to their counterparts in other plants have been well characterized. Comprehensive expression profile analysis revealed that two family genes display divergent expression pattern, which are regulated temporally and spatially during the process of seed development and germination. Our experiments also revealed that the expression of most genes in these two families is sensitively responsive to plant hormones and different abiotic stresses.

CONCLUSIONS: Genome-wide identification and comprehensive gene expression pattern analysis of papain-like and legumain-like proteases in rice suggests their multiple and cooperative roles in seed development and response to environmental variations, which provides several useful cues for further in-depth study.}, } @article {pmid29764366, year = {2018}, author = {Anselmetti, Y and Duchemin, W and Tannier, E and Chauve, C and Bérard, S}, title = {Phylogenetic signal from rearrangements in 18 Anopheles species by joint scaffolding extant and ancestral genomes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {96}, pmid = {29764366}, issn = {1471-2164}, mesh = {Algorithms ; Animals ; Anopheles/*genetics ; Computational Biology/*methods ; Evolution, Molecular ; Gene Order ; *Gene Rearrangement ; Genome, Insect ; Mosquito Vectors/*genetics ; Phylogeny ; Sex Chromosomes/genetics ; }, abstract = {BACKGROUND: Genomes rearrangements carry valuable information for phylogenetic inference or the elucidation of molecular mechanisms of adaptation. However, the detection of genome rearrangements is often hampered by current deficiencies in data and methods: Genomes obtained from short sequence reads have generally very fragmented assemblies, and comparing multiple gene orders generally leads to computationally intractable algorithmic questions.

RESULTS: We present a computational method, ADSEQ, which, by combining ancestral gene order reconstruction, comparative scaffolding and de novo scaffolding methods, overcomes these two caveats. ADSEQ provides simultaneously improved assemblies and ancestral genomes, with statistical supports on all local features. Compared to previous comparative methods, it runs in polynomial time, it samples solutions in a probabilistic space, and it can handle a significantly larger gene complement from the considered extant genomes, with complex histories including gene duplications and losses. We use ADSEQ to provide improved assemblies and a genome history made of duplications, losses, gene translocations, rearrangements, of 18 complete Anopheles genomes, including several important malaria vectors. We also provide additional support for a differentiated mode of evolution of the sex chromosome and of the autosomes in these mosquito genomes.

CONCLUSIONS: We demonstrate the method's ability to improve extant assemblies accurately through a procedure simulating realistic assembly fragmentation. We study a debated issue regarding the phylogeny of the Gambiae complex group of Anopheles genomes in the light of the evolution of chromosomal rearrangements, suggesting that the phylogenetic signal they carry can differ from the phylogenetic signal carried by gene sequences, more prone to introgression.}, } @article {pmid29764365, year = {2018}, author = {Valenzuela, D and Norri, T and Välimäki, N and Pitkänen, E and Mäkinen, V}, title = {Towards pan-genome read alignment to improve variation calling.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {87}, pmid = {29764365}, issn = {1471-2164}, mesh = {Access to Information ; *Genetic Variation ; Genome, Human ; Humans ; Internet ; Sequence Alignment ; Sequence Analysis, DNA/*methods ; Software ; Workflow ; }, abstract = {BACKGROUND: Typical human genome differs from the reference genome at 4-5 million sites. This diversity is increasingly catalogued in repositories such as ExAC/gnomAD, consisting of >15,000 whole-genomes and >126,000 exome sequences from different individuals. Despite this enormous diversity, resequencing data workflows are still based on a single human reference genome. Identification and genotyping of genetic variants is typically carried out on short-read data aligned to a single reference, disregarding the underlying variation.

RESULTS: We propose a new unified framework for variant calling with short-read data utilizing a representation of human genetic variation - a pan-genomic reference. We provide a modular pipeline that can be seamlessly incorporated into existing sequencing data analysis workflows. Our tool is open source and available online: https://gitlab.com/dvalenzu/PanVC .

CONCLUSIONS: Our experiments show that by replacing a standard human reference with a pan-genomic one we achieve an improvement in single-nucleotide variant calling accuracy and in short indel calling accuracy over the widely adopted Genome Analysis Toolkit (GATK) in difficult genomic regions.}, } @article {pmid29764364, year = {2018}, author = {He, D and Saha, S and Finkers, R and Parida, L}, title = {Efficient algorithms for polyploid haplotype phasing.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {110}, pmid = {29764364}, issn = {1471-2164}, mesh = {Algorithms ; Genome ; Genomics/*methods ; *Haplotypes ; *Polyploidy ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Inference of haplotypes, or the sequence of alleles along the same chromosomes, is a fundamental problem in genetics and is a key component for many analyses including admixture mapping, identifying regions of identity by descent and imputation. Haplotype phasing based on sequencing reads has attracted lots of attentions. Diploid haplotype phasing where the two haplotypes are complimentary have been studied extensively. In this work, we focused on Polyploid haplotype phasing where we aim to phase more than two haplotypes at the same time from sequencing data. The problem is much more complicated as the search space becomes much larger and the haplotypes do not need to be complimentary any more.

RESULTS: We proposed two algorithms, (1) Poly-Harsh, a Gibbs Sampling based algorithm which alternatively samples haplotypes and the read assignments to minimize the mismatches between the reads and the phased haplotypes, (2) An efficient algorithm to concatenate haplotype blocks into contiguous haplotypes.

CONCLUSIONS: Our experiments showed that our method is able to improve the quality of the phased haplotypes over the state-of-the-art methods. To our knowledge, our algorithm for haplotype blocks concatenation is the first algorithm that leverages the shared information across multiple individuals to construct contiguous haplotypes. Our experiments showed that it is both efficient and effective.}, } @article {pmid29764363, year = {2018}, author = {Noutahi, E and El-Mabrouk, N}, title = {GATC: a genetic algorithm for gene tree construction under the Duplication-Transfer-Loss model of evolution.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {102}, pmid = {29764363}, issn = {1471-2164}, mesh = {Algorithms ; Cyanobacteria/*genetics ; Evolution, Molecular ; Gene Duplication ; *Genes, Bacterial ; Genomics/*methods ; Internet ; Models, Genetic ; Multigene Family ; Phylogeny ; }, abstract = {BACKGROUND: Several methods have been developed for the accurate reconstruction of gene trees. Some of them use reconciliation with a species tree to correct, a posteriori, errors in gene trees inferred from multiple sequence alignments. Unfortunately the best fit to sequence information can be lost during this process.

RESULTS: We describe GATC, a new algorithm for reconstructing a binary gene tree with branch length. GATC returns optimal solutions according to a measure combining both tree likelihood (according to sequence evolution) and a reconciliation score under the Duplication-Transfer-Loss (DTL) model. It can either be used to construct a gene tree from scratch or to correct trees infered by existing reconstruction method, making it highly flexible to various input data types. The method is based on a genetic algorithm acting on a population of trees at each step. It substantially increases the efficiency of the phylogeny space exploration, reducing the risk of falling into local minima, at a reasonable computational time. We have applied GATC to a dataset of simulated cyanobacterial phylogenies, as well as to an empirical dataset of three reference gene families, and showed that it is able to improve gene tree reconstructions compared with current state-of-the-art algorithms.

CONCLUSION: The proposed algorithm is able to accurately reconstruct gene trees and is highly suitable for the construction of reference trees. Our results also highlight the efficiency of multi-objective optimization algorithms for the gene tree reconstruction problem. GATC is available on Github at: https://github.com/UdeM-LBIT/GATC .}, } @article {pmid29764362, year = {2018}, author = {de Molina, C and Serrano, E and Garcia-Blas, J and Carretero, J and Desco, M and Abella, M}, title = {GPU-accelerated iterative reconstruction for limited-data tomography in CBCT systems.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {171}, pmid = {29764362}, issn = {1471-2105}, abstract = {BACKGROUND: Standard cone-beam computed tomography (CBCT) involves the acquisition of at least 360 projections rotating through 360 degrees. Nevertheless, there are cases in which only a few projections can be taken in a limited angular span, such as during surgery, where rotation of the source-detector pair is limited to less than 180 degrees. Reconstruction of limited data with the conventional method proposed by Feldkamp, Davis and Kress (FDK) results in severe artifacts. Iterative methods may compensate for the lack of data by including additional prior information, although they imply a high computational burden and memory consumption.

RESULTS: We present an accelerated implementation of an iterative method for CBCT following the Split Bregman formulation, which reduces computational time through GPU-accelerated kernels. The implementation enables the reconstruction of large volumes (>10243 pixels) using partitioning strategies in forward- and back-projection operations. We evaluated the algorithm on small-animal data for different scenarios with different numbers of projections, angular span, and projection size. Reconstruction time varied linearly with the number of projections and quadratically with projection size but remained almost unchanged with angular span. Forward- and back-projection operations represent 60% of the total computational burden.

CONCLUSION: Efficient implementation using parallel processing and large-memory management strategies together with GPU kernels enables the use of advanced reconstruction approaches which are needed in limited-data scenarios. Our GPU implementation showed a significant time reduction (up to 48 ×) compared to a CPU-only implementation, resulting in a total reconstruction time from several hours to few minutes.}, } @article {pmid29764361, year = {2018}, author = {Liu, YC and Hong, HC and Yang, CD and Lee, WH and Huang, HT and Huang, HD}, title = {Ouroboros resembling competitive endogenous loop (ORCEL) in circular RNAs revealed through transcriptome sequencing dataset analysis.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {171}, pmid = {29764361}, issn = {1471-2164}, mesh = {Algorithms ; Computational Biology/methods ; Databases, Genetic ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; MicroRNAs/*genetics ; RNA/*genetics ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Emerging evidence indicates that Circular RNAs (circRNAs) exert post-transcriptional regulation of gene expression. A subclass of circRNA was found enriched with miRNA target sites. This evidence suggests that this kind of circRNA functions as natural miRNA sponge. Noticing the potential impacts of circular RNA research, we were motivated to identify novel circRNAs as well as putative circRNA-miRNA interactions through retroactive sourced transcriptome sequencing samples.

RESULTS: Through the analysis in 465 RNA-seq runs and 22 reports published in recent years, putatively circRNA sponged miRNA that had been experimentally verified targeting circRNA host gene were found. From this observation, supporting evidence of the competitive endogenous relationship of circRNAs and miRNAs targeting circRNA host genes can be observed. Given the self-regulation and self-induction nature of these circRNAs, this kind of hypothetical phenomenon was hereby called Ouroboros Resembling Competitive Endogenous Loop (ORCEL) in circular RNAs.

CONCLUSIONS: The fact that miRNA sponge circRNA originated from region miRNA target sites enriched regions, while genes encoded from these regions are conserved to be miRNA targets rationalize the existence of ORCEL.}, } @article {pmid29764360, year = {2018}, author = {Zeng, W and Wu, M and Jiang, R}, title = {Prediction of enhancer-promoter interactions via natural language processing.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 2}, pages = {84}, pmid = {29764360}, issn = {1471-2164}, mesh = {Cell Line, Tumor ; Computational Biology/*methods ; Databases, Genetic ; HeLa Cells ; Human Umbilical Vein Endothelial Cells ; Humans ; K562 Cells ; Natural Language Processing ; *Promoter Regions, Genetic ; *Regulatory Sequences, Nucleic Acid ; Sequence Analysis, DNA ; Unsupervised Machine Learning ; }, abstract = {BACKGROUND: Precise identification of three-dimensional genome organization, especially enhancer-promoter interactions (EPIs), is important to deciphering gene regulation, cell differentiation and disease mechanisms. Currently, it is a challenging task to distinguish true interactions from other nearby non-interacting ones since the power of traditional experimental methods is limited due to low resolution or low throughput.

RESULTS: We propose a novel computational framework EP2vec to assay three-dimensional genomic interactions. We first extract sequence embedding features, defined as fixed-length vector representations learned from variable-length sequences using an unsupervised deep learning method in natural language processing. Then, we train a classifier to predict EPIs using the learned representations in supervised way. Experimental results demonstrate that EP2vec obtains F1 scores ranging from 0.841~ 0.933 on different datasets, which outperforms existing methods. We prove the robustness of sequence embedding features by carrying out sensitivity analysis. Besides, we identify motifs that represent cell line-specific information through analysis of the learned sequence embedding features by adopting attention mechanism. Last, we show that even superior performance with F1 scores 0.889~ 0.940 can be achieved by combining sequence embedding features and experimental features.

CONCLUSIONS: EP2vec sheds light on feature extraction for DNA sequences of arbitrary lengths and provides a powerful approach for EPIs identification.}, } @article {pmid29763665, year = {2018}, author = {Rajter, Ľ and Vďačný, P}, title = {Selection and paucity of phylogenetic signal challenge the utility of alpha-tubulin in reconstruction of evolutionary history of free-living litostomateans (Protista, Ciliophora).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {534-544}, doi = {10.1016/j.ympev.2018.05.011}, pmid = {29763665}, issn = {1095-9513}, mesh = {Ciliophora/*classification/genetics ; Evolution, Molecular ; Genes, rRNA ; *Phylogeny ; Tubulin/chemistry/*genetics ; }, abstract = {The class Litostomatea represents a highly diverse but monophyletic group, uniting both free-living and endosymbiotic ciliates. Ribosomal RNA genes and ITS-region sequences helped to recognize and define the main litostomatean lineages, but did not provide enough phylogenetic signal to unambiguously resolve their interrelationships. In this study, we attempted to improve the resolution among main free-living predatory lineages by adding the gene coding for alpha-tubulin. However, our phylogenetic analyses challenged the performance of alpha-tubulin in reconstruction of evolutionary history of free-living litostomateans. We identified several mutually interconnected problems associated with the ciliate alpha-tubulin gene: the paucity of phylogenetic signal, molecular homoplasies and non-neutral evolution. Positive selection may generate molecular homoplasies (parallel evolution), while negative selection may cause a small number of changes and hence little phylogenetic informativness. Both problems were encountered in nucleotide and amino acid alpha-tubulin alignments, indicating an action of various selective pressures. Taking into account the involvement of alpha-tubulin in many essential biological processes, this protein could be so strongly affected by purifying selection that it even might have become an inappropriate molecular marker for reconstruction of phylogenetic relationships. Therefore, a great caution should be paid when tubulin genes are included in phylogenetic and/or phylogenomic analyses.}, } @article {pmid29763664, year = {2018}, author = {Brazenor, AK and Bertozzi, T and Miller, TL and Whittington, ID and Hutson, KS}, title = {DNA profiling reveals Neobenedenia girellae as the primary parasitic monogenean in global fisheries and aquaculture.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {130-137}, doi = {10.1016/j.ympev.2018.05.012}, pmid = {29763664}, issn = {1095-9513}, abstract = {Accurate identification of parasite species and strains is crucial to mitigate the risk of epidemics and emerging disease. Species of Neobenedenia are harmful monogenean ectoparasites that infect economically important bony fishes in aquaculture worldwide, however, the species boundaries between two of the most notorious taxa, N. melleni and N. girellae, has been a topic of contention for decades. Historically, identifications of Neobenedenia isolates have overwhelmingly been attributed to N. melleni, and it has been proposed that N. girellae is synonymous with N. melleni. We collected 33 Neobenedenia isolates from 22 host species spanning nine countries and amplified three genes including two nuclear (Histone 3 and 28S rDNA) and one mitochondrial (cytochrome b). Four major clades were identified using Maximum Likelihood and Bayesian inference analyses; clades A-D corresponding to N. girellae, N. melleni, N. longiprostata and N. pacifica, respectively. All unidentified isolates and the majority of Neobenedenia sequences from GenBank fell into clade A. The results of this study indicate that N. girellae is a separate species to N. melleni, and that a large proportion of previous samples identified as N. melleni may be erroneous and a revision of identifications is needed. The large diversity of host species that N. girellae is able to infect as determined in this study and the geographic range in which it is present (23.8426°S and 24.1426°N) makes it a globally cosmopolitan species and a threat to aquaculture industries around the world.}, } @article {pmid29763663, year = {2018}, author = {Patel, N and Li, CX and Zhang, LB and Barrington, DS}, title = {Biodiversity and apomixis: Insights from the East-Asian holly ferns in Polystichum section Xiphopolystichum.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {345-355}, doi = {10.1016/j.ympev.2018.05.003}, pmid = {29763663}, issn = {1095-9513}, } @article {pmid29763662, year = {2018}, author = {Korovesi, AG and Ntertilis, M and Kouvelis, VN}, title = {Mt-rps3 is an ancient gene which provides insight into the evolution of fungal mitochondrial genomes.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {74-86}, doi = {10.1016/j.ympev.2018.04.037}, pmid = {29763662}, issn = {1095-9513}, abstract = {The nuclear ribosomal protein S3 (Rps3) is implicated in the assembly of the ribosomal small subunit. Fungi and plants present a gene copy in their mitochondrial (mt) genomes. An analysis of 303 complete fungal mt genomes showed that, when rps3 is found, it is either a free-standing gene or an anchored gene within the omega intron of the rnl gene. Early divergent fungi, Basidiomycota and all yeasts but the CTG group belong to the first case, and Pezizomycotina to the second. Its position, size and genetic code employed are conserved within species of the same Order. Size variability is attributed to different number of repeats. These repeats consist of AT-rich sequences. MtRps3 proteins lack the KH domain, necessary for binding to rRNA, in their N-terminal region. Their C-terminal region is conserved in all Domains of life. Phylogenetic analysis showed that nuclear and mtRps3 proteins are descendants of archaeal and a-proteobacterial homologues, respectively. Thus, fungal mt-rps3 gene is an ancient gene which evolved within the endosymbiotic model and presents different evolutionary routes: (a) coming from a-proteobacteria, it was relocated to another region of the mt genome, (b) via its insertion to the omega intron, it was transferred to the nucleus and/or got lost, and (c) it was re-routed to the mt genome again. Today, Basidiomycota and Saccharomycetales seem to follow the first evolutionary route and almost all Pezizomycotina support the second scenario with their exceptions being the result of the third scenario, i.e., the gene's re-entry to the mt genome.}, } @article {pmid29762743, year = {2018}, author = {Khrameeva, E and Kurochkin, I and Bozek, K and Giavalisco, P and Khaitovich, P}, title = {Lipidome Evolution in Mammalian Tissues.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1947-1957}, pmid = {29762743}, issn = {1537-1719}, abstract = {Lipids are essential structural and functional components of cells. Little is known, however, about the evolution of lipid composition in different tissues. Here, we report a large-scale analysis of the lipidome evolution in six tissues of 32 species representing primates, rodents, and bats. While changes in genes' sequence and expression accumulate proportionally to the phylogenetic distances, <2% of the lipidome evolves this way. Yet, lipids constituting this 2% cluster in specific functions shared among all tissues. Among species, human show the largest amount of species-specific lipidome differences. Many of the uniquely human lipidome features localize in the brain cortex and cluster in specific pathways implicated in cognitive disorders.}, } @article {pmid29762105, year = {2018}, author = {Wang, KL and Song, ZM and Rong, CH and Hao, LY and Lai, QL and Li, SF and Xu, Y}, title = {Kandeliimicrobium roseum gen. nov., sp. nov., a new member of the family Rhodobacteraceae isolated from mangrove rhizosphere soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2158-2164}, doi = {10.1099/ijsem.0.002773}, pmid = {29762105}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hong Kong ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizophoraceae ; *Rhizosphere ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, non-flagellated, short rod-shaped bacterium, designated XY-R6T, was isolated from the rhizosphere soil of a mangrove plant, Kandelia candel (L.) Druce, in Mai Po Nature Reserve, Hong Kong. Growth of strain XY-R6T was observed at pH 5.0-9.5 (optimum 6.5-8.0), between 8 and 42 °C (optimum 28-34 °C), and in the presence of 0-9.5 % (w/v) NaCl (optimum 1-4 %). The predominant isoprenoid quinone was ubiquinone-10. The major fatty acids were summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c) (55.61 %), C19 : 0cycloω8c (21.59 %) and C16 : 0 (11.24 %). The major polar lipids were phosphatidylglycerol, phosphatidylethanolamine, aminolipid, phosphatidylcholine and diphosphatidylglycerol. The genomic DNA G+C content of strain XY-R6T was 69.3 mol%. Phylogenetic analyses, based on 16S rRNA gene sequences, revealed that strain XY-R6T belonged to the family Rhodobacteraceae of the class Alphaproteobacteria and formed a distinct lineage, showing the highest gene sequence similarities to the members of genus Wenxinia(94.5-94.3 %), followed by the genera Profundibacterium (94.3 %), Defluviimonas(93.8-92.5 %), Oceanicola (93.8 %) and Cereibacter (93.7 %). Similarities to other genera within the family Rhodobacteraceae were below 94.0 %. Based on comprehensive phenotypic, phylogenetic and chemotaxonomic characterization, it is indicated that strain XY-R6T represents a novel species of a new genus in the family Rhodobacteraceae, for which the name Kandeliimicrobium roseum gen. nov., sp. nov. is proposed, with XY-R6T (=MCCC 1K01498T=KCTC 52266T=DSM 104294T) as the type strain.}, } @article {pmid29761484, year = {2018}, author = {Hajduk, GK and Cockburn, A and Margraf, N and Osmond, HL and Walling, CA and Kruuk, LEB}, title = {Inbreeding, inbreeding depression, and infidelity in a cooperatively breeding bird.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, pmid = {29761484}, issn = {1558-5646}, abstract = {Inbreeding depression plays a major role in shaping mating systems: in particular, inbreeding avoidance is often proposed as a mechanism explaining extra-pair reproduction in socially monogamous species. This suggestion relies on assumptions that are rarely comprehensively tested: that inbreeding depression is present, that higher kinship between social partners increases infidelity, and that infidelity reduces the frequency of inbreeding. Here, we test these assumptions using 26 years of data for a cooperatively breeding, socially monogamous bird with high female infidelity, the superb fairy-wren (Malurus cyaneus). Although inbred individuals were rare (∼6% of offspring), we found evidence of inbreeding depression in nestling mass (but not in fledgling survival). Mother-son social pairings resulted in 100% infidelity, but kinship between a social pair did not otherwise predict female infidelity. Nevertheless, extra-pair offspring were less likely to be inbred than within-pair offspring. Finally, the social environment (the number of helpers in a group) did not affect offspring inbreeding coefficients or inbreeding depression levels. In conclusion, despite some agreement with the assumptions that are necessary for inbreeding avoidance to drive infidelity, the apparent scarcity of inbreeding events and the observed levels of inbreeding depression seem insufficient to explain the ubiquitous infidelity in this system, beyond the mother-son mating avoidance.}, } @article {pmid29761217, year = {2018}, author = {Park, S and Won, SM and Yoon, JH}, title = {Dokdonia ponticola sp. nov., A Carrageenan-Degrading Bacterium of the Family Flavobacteriaceae Isolated from Seawater.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29761217}, issn = {1432-0991}, support = {project on survey of indigenous species of Korea//National Institute of Biological Resources/ ; PJ012956//Rural Development Administration/ ; }, abstract = {A Gram-stain-negative, aerobic, non-motile, and carrageenan-degrading bacterial strain, designated OISW-17T, was isolated from seawater around Oido, an island of South Korea, and its taxonomic position was determined using a polyphasic study. Optimal growth of the novel strain occurred at 20-25 °C and in the presence of 2.0% (w/v) NaCl. Phylogenetic trees using 16S rRNA gene sequences showed that strain OISW-17T forms a cluster with the type strains of Dokdonia species. The novel strain exhibited 16S rRNA gene sequence similarities of 95.7-96.3% to the type strains of Dokdonia species and of < 93.4% to the type strains of the other recognized species. Menaquinone-6 (MK-6) was found as the predominant menaquinone and iso-C15:0, iso-C15:1 G, and iso-C17:0 3-OH were the major fatty acids. Phosphatidylethanolamine, one unidentified lipid, and one unidentified aminolipid were major polar lipids detected in strain OISW-17T. Strain OISW-17T had DNA G+C content of 39.7 mol%. The differential phenotypic characteristics, along with the phylogenetic data, made strain OISW-17T to be distinct from recognized species of the genus Dokdonia. On the basis of the data given, strain OISW-17T represents a novel species of the genus Dokdonia, for which the name Dokdonia ponticola sp. nov. is proposed. The type strain of the novel species is OISW-17T (= KACC 19437T = KCTC 62187T = CGMCC 1.16527T).}, } @article {pmid29760911, year = {2018}, author = {Zogg, GP and Travis, SE and Brazeau, DA}, title = {Strong associations between plant genotypes and bacterial communities in a natural salt marsh.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4721-4730}, pmid = {29760911}, issn = {2045-7758}, abstract = {Although microbial communities have been shown to vary among plant genotypes in a number of experiments in terrestrial ecosystems, relatively little is known about this relationship under natural conditions and outside of select model systems. We reasoned that a salt marsh ecosystem, which is characterized by twice-daily flooding by tides, would serve as a particularly conservative test of the strength of plant-microbial associations, given the high degree of abiotic regulation of microbial community assembly resulting from alternating periods of inundation and exposure. Within a salt marsh in the northeastern United States, we characterized genotypes of the foundational plant Spartina alterniflora using microsatellite markers, and bacterial metagenomes within marsh soil based on pyrosequencing. We found significant differences in bacterial community composition and diversity between bulk and rhizosphere soil, and that the structure of rhizosphere communities varied depending on the growth form of, and genetic variation within, the foundational plant S. alterniflora. Our results indicate that there are strong plant-microbial associations within a natural salt marsh, thereby contributing to a growing body of evidence for a relationship between plant genotypes and microbial communities from terrestrial ecosystems and suggest that principles of community genetics apply to this wetland type.}, } @article {pmid29760910, year = {2018}, author = {Ng, SH and Stat, M and Bunce, M and Simmons, LW}, title = {The influence of diet and environment on the gut microbial community of field crickets.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4704-4720}, pmid = {29760910}, issn = {2045-7758}, abstract = {The extent to which diet and environment influence gut community membership (presence or absence of taxa) and structure (individual taxon abundance) is the subject of growing interest in microbiome research. Here, we examined the gut bacterial communities of three cricket groups: (1) wild caught field crickets, (2) laboratory-reared crickets fed cat chow, and (3) laboratory-reared crickets fed chemically defined diets. We found that both environment and diet greatly altered the structure of the gut bacterial community. Wild crickets had greater gut microbial diversity and higher Firmicutes to Bacteroidetes ratios, in contrast to laboratory-reared crickets. Predictive metagenomes revealed that laboratory-reared crickets were significantly enriched in amino acid degradation pathways, while wild crickets had a higher relative abundance of peptidases that would aid in amino acid release. Although wild and laboratory animals differ greatly in their bacterial communities, we show that the community proportional membership remains stable from Phylum to Family taxonomic levels regardless of differences in environment and diet, suggesting that endogenous factors, such as host genetics, have greater control in shaping gut community membership.}, } @article {pmid29760909, year = {2018}, author = {Zhang, W and Li, N and Tang, X and Liu, N and Zhao, W}, title = {Changes in intestinal microbiota across an altitudinal gradient in the lizard Phrynocephalus vlangalii.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4695-4703}, pmid = {29760909}, issn = {2045-7758}, abstract = {High altitude is an important driving force in animal evolution. However, the effect of altitude on gut microbial communities in reptiles has not been examined in detail. Here, we investigated the intestinal microbiota of three populations of the lizard Phrynocephalus vlangalii living at different altitudes using 16S rRNA gene sequencing. Bacteroidetes, Firmicutes, and Proteobacteria were the most abundant phyla. Bacteroides, Odoribacter, and Parabacteroides were the most abundant genera. Significant differences in the intestinal microbiota composition were found among the three populations from different altitudes. The proportions of Verrucomicrobia and Akkermansia decreased, whereas Bacteroides increased significantly with altitude. Greater abundance of Bacteroides at higher altitude led to the fractional increase in the phylum Bacteroides relative to other phyla. Hypoxia may be the main factor that caused intestinal microbiota variation in P. vlangalii along the altitude gradient. Overall, our study suggested that the community composition and structure of intestinal microbiota of the lizard P. vlangalii varied along altitudes, and such differences likely play a certain role in highland adaptation. Our findings warrant a further study that would determine whether ambient and body temperatures play a key role in the modulation of intestinal microbiota in reptiles.}, } @article {pmid29760908, year = {2018}, author = {Harant, UK and Santon, M and Bitton, PP and Wehrberger, F and Griessler, T and Meadows, MG and Champ, CM and Michiels, NK}, title = {Do the fluorescent red eyes of the marine fish Tripterygion delaisi stand out? In situ and in vivo measurements at two depths.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4685-4694}, pmid = {29760908}, issn = {2045-7758}, abstract = {Since the discovery of red fluorescence in fish, much effort has been invested to elucidate its potential functions, one of them being signaling. This implies that the combination of red fluorescence and reflection should generate a visible contrast against the background. Here, we present in vivo iris radiance measurements of Tripterygion delaisi under natural light conditions at 5 and 20 m depth. We also measured substrate radiance of shaded and exposed foraging sites at those depths. To assess the visual contrast of the red iris against these substrates, we used the receptor noise model for chromatic contrasts and Michelson contrast for achromatic calculations. At 20 m depth, T. delaisi iris radiance generated strong achromatic contrasts against substrate radiance, regardless of exposure, and despite substrate fluorescence. Given that downwelling light above 600 nm is negligible at this depth, we can attribute this effect to iris fluorescence. Contrasts were weaker in 5 m. Yet, the pooled radiance caused by red reflection and fluorescence still exceeded substrate radiance for all substrates under shaded conditions and all but Jania rubens and Padina pavonia under exposed conditions. Due to the negative effects of anesthesia on iris fluorescence, these estimates are conservative. We conclude that the requirements to create visual brightness contrasts are fulfilled for a wide range of conditions in the natural environment of T. delaisi.}, } @article {pmid29760907, year = {2018}, author = {Benoit, D and Jackson, DA and Ridgway, MS}, title = {Assessing the impacts of imperfect detection on estimates of diversity and community structure through multispecies occupancy modeling.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4676-4684}, pmid = {29760907}, issn = {2045-7758}, abstract = {Detecting all species in a given survey is challenging, regardless of sampling effort. This issue, more commonly known as imperfect detection, can have negative impacts on data quality and interpretation, most notably leading to false absences for rare or difficult-to-detect species. It is important that this issue be addressed, as estimates of species richness are critical to many areas of ecological research and management. In this study, we set out to determine the impacts of imperfect detection, and decisions about thresholds for inclusion in occupancy, on estimates of species richness and community structure. We collected data from a stream fish assemblage in Algonquin Provincial Park to be used as a representation of ecological communities. We then used multispecies occupancy modeling to estimate species-specific occurrence probabilities while accounting for imperfect detection, thus creating a more informed dataset. This dataset was then compared to the original to see where differences occurred. In our analyses, we demonstrated that imperfect detection can lead to large changes in estimates of species richness at the site level and summarized differences in the community structure and sampling locations, represented through correspondence analyses.}, } @article {pmid29760906, year = {2018}, author = {Vidal-García, M and Bandara, L and Keogh, JS}, title = {ShapeRotator: An R tool for standardized rigid rotations of articulated three-dimensional structures with application for geometric morphometrics.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4669-4675}, pmid = {29760906}, issn = {2045-7758}, abstract = {The quantification of complex morphological patterns typically involves comprehensive shape and size analyses, usually obtained by gathering morphological data from all the structures that capture the phenotypic diversity of an organism or object. Articulated structures are a critical component of overall phenotypic diversity, but data gathered from these structures are difficult to incorporate into modern analyses because of the complexities associated with jointly quantifying 3D shape in multiple structures. While there are existing methods for analyzing shape variation in articulated structures in two-dimensional (2D) space, these methods do not work in 3D, a rapidly growing area of capability and research. Here, we describe a simple geometric rigid rotation approach that removes the effect of random translation and rotation, enabling the morphological analysis of 3D articulated structures. Our method is based on Cartesian coordinates in 3D space, so it can be applied to any morphometric problem that also uses 3D coordinates (e.g., spherical harmonics). We demonstrate the method by applying it to a landmark-based dataset for analyzing shape variation using geometric morphometrics. We have developed an R tool (ShapeRotator) so that the method can be easily implemented in the commonly used R package geomorph and MorphoJ software. This method will be a valuable tool for 3D morphological analyses in articulated structures by allowing an exhaustive examination of shape and size diversity.}, } @article {pmid29760905, year = {2018}, author = {Tay, YC and Ng, DJJ and Loo, JB and Huang, D and Cai, Y and Yeo, DCJ and Meier, R}, title = {Roads to isolation: Similar genomic history patterns in two species of freshwater crabs with contrasting environmental tolerances and range sizes.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4657-4668}, pmid = {29760905}, issn = {2045-7758}, abstract = {Freshwater species often show high levels of endemism and risk of extinction owing to their limited dispersal abilities. This is exemplified by the stenotopic freshwater crab, Johora singaporensis which is one of the world's 100 most threatened species, and currently inhabits less than 0.01 km2 of five low order hill streams within the highly urbanized island city-state of Singapore. We compared populations of J. singaporensis with that of the non-threatened, widespread, abundant, and eurytopic freshwater crab, Parathelphusa maculata, and found surprisingly high congruence between their population genomic histories. Based on 2,617 and 2,470 genome-wide SNPs mined via the double-digest restriction-associated DNA sequencing method for ~90 individuals of J. singaporensis and P. maculata, respectively, the populations are strongly isolated (FST = 0.146-0.371), have low genetic diversity for both species (also for COI), and show signatures of recent genetic bottlenecks. The most genetically isolated populations for both species are separated from other populations by one of the oldest roads in Singapore. These results suggest that anthropogenic developments may have impacted stream-dependent species in a uniform manner, regardless of ubiquity, habitat preference, or dispersal modes of the species. While signs of inbreeding were not detected for the critically endangered species, the genetic distinctiveness and low diversity of the populations call for genetic rescue and connecting corridors between the remaining fragments of the natural habitat.}, } @article {pmid29760904, year = {2018}, author = {Markle, TM and Kozak, KH}, title = {Low acclimation capacity of narrow-ranging thermal specialists exposes susceptibility to global climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4644-4656}, pmid = {29760904}, issn = {2045-7758}, abstract = {Thermal acclimation is hypothesized to offer a selective advantage in seasonal habitats and may underlie disparities in geographic range size among closely-related species with similar ecologies. Understanding this relationship is also critical for identifying species that are more sensitive to warming climates. Here, we study North American plethodontid salamanders to investigate whether acclimation ability is associated with species' latitudinal extents and the thermal range of the environments they inhabit. We quantified variation in thermal physiology by measuring standard metabolic rate (SMR) at different test and acclimation temperatures for 16 species of salamanders with varying latitudinal extents. A phylogenetically-controlled Markov chain Monte Carlo generalized linear mixed model (MCMCglmm) was then employed to determine whether there are differences in SMR between wide- and narrow-ranging species at different acclimation temperatures. In addition, we tested for a relationship between the acclimation ability of species and the environmental temperature ranges they inhabit. Further, we investigated if there is a trade-off between critical thermal maximum (CTMax) and thermal acclimation ability. MCMCglmm results show a significant difference in acclimation ability between wide and narrow-ranging temperate salamanders. Salamanders with wide latitudinal distributions maintain or slightly increase SMR when subjected to higher test and acclimation temperatures, whereas several narrow-ranging species show significant metabolic depression. We also found significant, positive relationships between acclimation ability and environmental thermal range, and between acclimation ability and CTMax. Wide-ranging salamander species exhibit a greater capacity for thermal acclimation than narrow-ranging species, suggesting that selection for acclimation ability may have been a key factor enabling geographic expansion into areas with greater thermal variability. Further, given that narrow-ranging salamanders are found to have both poor acclimation ability and lower tolerance to warm temperatures, they are likely to be more susceptible to environmental warming associated with anthropogenic climate change.}, } @article {pmid29760903, year = {2018}, author = {Su, J and Hegab, IM and Ji, W and Nan, Z}, title = {Function-related Drivers of Skull Morphometric Variation and Sexual Size Dimorphism in a Subterranean Rodent, Plateau Zokor (Eospalax baileyi).}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4631-4643}, pmid = {29760903}, issn = {2045-7758}, abstract = {Sexual dimorphism is prevalent in most living organisms. The difference in size between sexes of a given species is generally known as sexual size dimorphism (SSD). The magnitude of the SSD is determined by Rensch's rule where size dimorphism increases with increasing body size when the male is the larger sex and decreases with increasing average body size when the female is the larger sex. The unique underground environment that zokors (Eospalax baileyi) live under in the severe habitat of the Qinghai-Tibetan Plateau (QTP) could create SSD selection pressures that may or may not be supported by Rensch's rule, making this scientific question worthy of investigation. In this study, we investigated the individual variation between sexes in body size and SSD of plateau zokors using measurements of 19 morphological traits. We also investigated the evolutionary mechanisms underlying SSD in plateau zokors. Moreover, we applied Rensch's rule to all extant zokor species. Our results showed male-biased SSD in plateau zokors: The body- and head-related measurements were greater in males than in females. Linear regression analysis between body length, body weight, and carcass weight showed significant relationships with some traits such as skull length, lower incisor length, and tympanic bulla width, which might support our prediction that males have faster growth rates than females. Further, the SSD pattern corroborated the assumption of Rensch's rule in plateau zokors but not in the other zokor species. Our findings suggest that the natural underground habitat and behavioral differences between sexes can generate selection pressures on male traits and contribute to the evolution of SSD in plateau zokors.}, } @article {pmid29760902, year = {2018}, author = {Quintero-Galvis, JF and Paleo-López, R and Solano-Iguaran, JJ and Poupin, MJ and Ledger, T and Gaitan-Espitia, JD and Antoł, A and Travisano, M and Nespolo, RF}, title = {Exploring the evolution of multicellularity in Saccharomyces cerevisiae under bacteria environment: An experimental phylogenetics approach.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4619-4630}, pmid = {29760902}, issn = {2045-7758}, abstract = {There have been over 25 independent unicellular to multicellular evolutionary transitions, which have been transformational in the complexity of life. All of these transitions likely occurred in communities numerically dominated by unicellular organisms, mostly bacteria. Hence, it is reasonable to expect that bacteria were involved in generating the ecological conditions that promoted the stability and proliferation of the first multicellular forms as protective units. In this study, we addressed this problem by analyzing the occurrence of multicellularity in an experimental phylogeny of yeasts (Sacharomyces cerevisiae) a model organism that is unicellular but can generate multicellular clusters under some conditions. We exposed a single ancestral population to periodic divergences, coevolving with a cocktail of environmental bacteria that were inoculated to the environment of the ancestor, and compared to a control (no bacteria). We quantified culturable microorganisms to the level of genera, finding up to 20 taxa (all bacteria) that competed with the yeasts during diversification. After 600 generations of coevolution, the yeasts produced two types of multicellular clusters: clonal and aggregative. Whereas clonal clusters were present in both treatments, aggregative clusters were only present under the bacteria treatment and showed significant phylogenetic signal. However, clonal clusters showed different properties if bacteria were present as follows: They were more abundant and significantly smaller than in the control. These results indicate that bacteria are important modulators of the occurrence of multicellularity, providing support to the idea that they generated the ecological conditions-promoting multicellularity.}, } @article {pmid29760901, year = {2018}, author = {Finnerty, PB and Shine, R and Brown, GP}, title = {Survival of the feces: Does a nematode lungworm adaptively manipulate the behavior of its cane toad host?.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4606-4618}, pmid = {29760901}, issn = {2045-7758}, abstract = {Parasites can enhance their fitness by modifying the behavior of their hosts in ways that increase rates of production and transmission of parasite larvae. We used an antihelminthic drug to experimentally alter infections of lungworms (Rhabdias pseudosphaerocephala) in cane toads (Rhinella marina). We then compared subsequent behaviors of dewormed toads versus toads that retained infections. Both in the laboratory and in the field, the presence of parasites induced hosts to select higher body temperatures (thereby increasing rates of lungworm egg production), to defecate in moister sites, and to produce feces with higher moisture content (thereby enhancing survival of larvae shed in feces). Because those behavioral modifications enhance rather than decrease parasite fitness, they are likely to have arisen as adaptive manipulations of host behavior rather than as host adaptations to combat infection or as nonadaptive consequences of infection on host physiology. However, the mechanisms by which lungworms alter cane toad thermal preference and defecation are not known. Although many examples of host manipulation by parasites involve intermediate hosts facilitating their own demise, our findings indicate that manipulation of definitive hosts can be as subtle as when and where to defecate.}, } @article {pmid29760900, year = {2018}, author = {Zablocki-Thomas, PB and Herrel, A and Hardy, I and Rabardel, L and Perret, M and Aujard, F and Pouydebat, E}, title = {Personality and performance are affected by age and early life parameters in a small primate.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4598-4605}, pmid = {29760900}, issn = {2045-7758}, abstract = {A whole suite of parameters is likely to influence the behavior and performance of individuals as adults, including correlations between phenotypic traits or an individual's developmental context. Here, we ask the question whether behavior and physical performance traits are correlated and how early life parameters such as birth weight, litter size, and growth can influence these traits as measured during adulthood. We studied 486 captive gray mouse lemurs (Microcebus murinus) and measured two behavioral traits and two performance traits potentially involved in two functions: exploration behavior with pull strength and agitation score with bite force. We checked for the existence of behavioral consistency in behaviors and explored correlations between behavior, performance, morphology. We analyzed the effect of birth weight, growth, and litter size, while controlling for age, sex, and body weight. Behavior and performance were not correlated with one another, but were both influenced by age. Growth rate had a positive effect on adult morphology, and birth weight significantly affected emergence latency and bite force. Grip strength was not directly affected by early life traits, but bite performance and exploration behavior were impacted by birth weight. This study shows how early life parameters impact personality and performance.}, } @article {pmid29760899, year = {2018}, author = {Chen, H and Ma, L and Xin, X and Liu, J and Wang, R}, title = {Plant community responses to increased precipitation and belowground litter addition: Evidence from a 5-year semiarid grassland experiment.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4587-4597}, pmid = {29760899}, issn = {2045-7758}, abstract = {Global climate change is predicted to stimulate primary production and consequently increases litter inputs. Changing precipitation regimes together with enhanced litter inputs may affect plant community composition and structure, with consequent influence on diversity and ecosystem functioning. Responses of plant community to increased precipitation and belowground litter addition were examined lasting 5 years in a semiarid temperate grassland of northeastern China. Increased precipitation enhanced community species richness and abundance of annuals by 16.8% and 44%, but litter addition suppressed them by 25% and 54.5% after 5 years, respectively. During the study period, perennial rhizome grasses and forbs had consistent negative relationship under ambient plots, whereas positive relationship between the two functional groups was found under litter addition plots after 5 years. In addition, increased precipitation and litter addition showed significant interaction on community composition, because litter addition significantly increased biomass and abundance of rhizome grasses under increased precipitation plots but had no effect under ambient precipitation levels. Our findings emphasize the importance of water availability in modulating the responses of plants community to potentially enhanced litter inputs in the semiarid temperate grassland.}, } @article {pmid29760898, year = {2018}, author = {McFarlane, SE and Ålund, M and Sirkiä, PM and Qvarnström, A}, title = {Difference in plasticity of resting metabolic rate - the proximate explanation to different niche breadth in sympatric Ficedula flycatchers.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4575-4586}, pmid = {29760898}, issn = {2045-7758}, abstract = {Variation in relative fitness of competing recently formed species across heterogeneous environments promotes coexistence. However, the physiological traits mediating such variation in relative fitness have rarely been identified. Resting metabolic rate (RMR) is tightly associated with life history strategies, thermoregulation, diet use, and inhabited latitude and could therefore moderate differences in fitness responses to fluctuations in local environments, particularly when species have adapted to different climates in allopatry. We work in a long-term study of collared (Ficedula albicollis) and pied flycatchers (Ficedula hypoleuca) in a recent hybrid zone located on the Swedish island of Öland in the Baltic Sea. Here, we explore whether differences in RMR match changes in relative performance of growing flycatcher nestlings across environmental conditions using an experimental approach. The fitness of pied flycatchers has previously been shown to be less sensitive to the mismatch between the peak in food abundance and nestling growth among late breeders. Here, we find that pied flycatcher nestlings have lower RMR in response to higher ambient temperatures (associated with low food availability). We also find that experimentally relaxed nestling competition is associated with an increased RMR in this species. In contrast, collared flycatcher nestlings did not vary their RMR in response to these environmental factors. Our results suggest that a more flexible nestling RMR in pied flycatchers is responsible for the better adaptation of pied flycatchers to the typical seasonal changes in food availability experienced in this hybrid zone. Generally, subtle physiological differences that have evolved when species were in allopatry may play an important role to patterns of competition, coexistence, or displacements between closely related species in secondary contact.}, } @article {pmid29760897, year = {2018}, author = {Martin, JM and Mead, JI and Barboza, PS}, title = {Bison body size and climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4564-4574}, pmid = {29760897}, issn = {2045-7758}, abstract = {The relationship between body size and temperature of mammals is poorly resolved, especially for large keystone species such as bison (Bison bison). Bison are well represented in the fossil record across North America, which provides an opportunity to relate body size to climate within a species. We measured the length of a leg bone (calcaneal tuber, DstL) in 849 specimens from 60 localities that were dated by stratigraphy and 14C decay. We estimated body mass (M) as M = (DstL/11.49)3. Average annual temperature was estimated from δ18O values in the ice cores from Greenland. Calcaneal tuber length of Bison declined over the last 40,000 years, that is, average body mass was 37% larger (910 ± 50 kg) than today (665 ± 21 kg). Average annual temperature has warmed by 6°C since the Last Glacial Maximum (~24-18 kya) and is predicted to further increase by 4°C by the end of the 21st century. If body size continues to linearly respond to global temperature, Bison body mass will likely decline by an additional 46%, to 357 ± 54 kg, with an increase of 4°C globally. The rate of mass loss is 41 ± 10 kg per°C increase in global temperature. Changes in body size of Bison may be a result of migration, disease, or human harvest but those effects are likely to be local and short-term and not likely to persist over the long time scale of the fossil record. The strong correspondence between body size of bison and air temperature is more likely the result of persistent effects on the ability to grow and the consequences of sustaining a large body mass in a warming environment. Continuing rises in global temperature will likely depress body sizes of bison, and perhaps other large grazers, without human intervention.}, } @article {pmid29760896, year = {2018}, author = {Magnúsdóttir, H and Pálsson, S and Westfall, KM and Jónsson, ZO and Örnólfsdóttir, EB}, title = {Shell morphology and color of the subtidal whelk Buccinum undatum exhibit fine-scaled spatial patterns.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4552-4563}, pmid = {29760896}, issn = {2045-7758}, abstract = {Geographical patterns in morphology can be the result of divergence among populations due to neutral or selective changes and/or phenotypic plasticity in response to different environments. Marine gastropods are ideal subjects on which to explore these patterns, by virtue of the remarkable intraspecific variation in life-history traits and morphology often observed across relatively small spatial scales. The ubiquitous N-Atlantic common whelk (Buccinum undatum) is well known for spatial variation in life-history traits and morphology. Previous studies on genetic population structure have revealed that it exhibits significant differentiation across geographic distances. Within Breiðafjörður Bay, a large and shallow bay in W-Iceland, genetic differentiation was demonstrated between whelks from sites separated by just 20 km. Here, we extended our previous studies on the common whelk in Breiðafjörður Bay by quantifying phenotypic variation in shell morphology and color throughout the Bay. We sought to test whether trait differentiation is dependent on geographic distance and/or environmental variability. Whelk in Breiðafjörður Bay displayed fine-scale patterns of spatial variation in shape, thickness, and color diversity. Differentiation increased with increasing distance between populations, indicating that population connectivity is limited. Both shape and color varied along a gradient from the inner part of the bay in the east to the outer part in the west. Whelk shells in the innermost part of Breiðafjörður Bay were thick with an elongate shell, round aperture, and low color diversity, whereas in the outer part of the bay the shells were thinner, rounder, with a more elongate aperture and richer color diversity. Significant site-specific difference in shell traits of the common whelk in correlation with environmental variables indicates the presence of local ecotypes and limited demographic connectivity.}, } @article {pmid29760895, year = {2018}, author = {Šmejkal, M and Ricard, D and Sajdlová, Z and Čech, M and Vejřík, L and Blabolil, P and Vejříková, I and Prchalová, M and Vašek, M and Souza, AT and Brönmark, C and Peterka, J}, title = {Can species-specific prey responses to chemical cues explain prey susceptibility to predation?.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4544-4551}, pmid = {29760895}, issn = {2045-7758}, abstract = {The perception of danger represents an essential ability of prey for gaining an informational advantage over their natural enemies. Especially in complex environments or at night, animals strongly rely on chemoreception to avoid predators. The ability to recognize danger by chemical cues and subsequent adaptive responses to predation threats should generally increase prey survival. Recent findings suggest that European catfish (Silurus glanis) introduction induce changes in fish community and we tested whether the direction of change can be attributed to differences in chemical cue perception. We tested behavioral response to chemical cues using three species of freshwater fish common in European water: rudd (Scardinius erythrophthalmus), roach (Rutilus rutilus), and perch (Perca fluviatilis). Further, we conducted a prey selectivity experiment to evaluate the prey preferences of the European catfish. Roach exhibited the strongest reaction to chemical cues, rudd decreased use of refuge and perch did not alter any behavior in the experiment. These findings suggest that chemical cue perception might be behind community data change and we encourage collecting more community data of tested prey species before and after European catfish introduction to test the hypothesis. We conclude that used prey species can be used as a model species to verify whether chemical cue perception enhances prey survival.}, } @article {pmid29760894, year = {2018}, author = {Jiang, F}, title = {Bioclimatic and altitudinal variables influence the potential distribution of canine parvovirus type 2 worldwide.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4534-4543}, pmid = {29760894}, issn = {2045-7758}, abstract = {Canine parvovirus type 2 (CPV-2) is extremely contagious and causes high rate of morbidity to many wild carnivores. It has three variants (CPV-2a, CPV-2b, and CPV-2c) that are distributed worldwide with different frequencies and levels of genetic and antigenic variability. The disease poses a threat to the healthy survival and reproduction of wildlife. The research on the relationship between CPV-2 epidemic and environmental variables is lacking. To fill this research gap, we used maximum entropy (MaxEnt) approach with principal component analysis (PCA) to evaluate the relation between CPV-2 and environmental variables and to create a world risk map for this disease. According to the PCA results, 18 environmental variables were selected from 68 variables for subsequent analyses. MaxEnt showed that annual mean temperature, isothermality, altitude, November precipitation, maximum temperature of warmest month, and precipitation of warmest quarter were the six most important variables associated with CPV-2 distribution, with a total of 77.7% percent contribution. The risk of this disease between 18°N and 47°N was high, especially in the east of China and the United States. These results support further prediction of risk factors for this virus to help secure the health and sustainable survival of wild carnivores.}, } @article {pmid29760893, year = {2018}, author = {Loo, J and Kennington, WJ and de Lestang, S and How, J and Evans, JP}, title = {High levels of polyandry, but limited evidence for multiple paternity, in wild populations of the western rock lobster (Panulirus cygnus).}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4525-4533}, pmid = {29760893}, issn = {2045-7758}, abstract = {Polyandry, where multiple mating by females results in the temporal and spatial overlap of ejaculates from two or more males, is taxonomically widespread and occurs in varying frequencies within and among species. In decapods (crabs, lobsters, crayfish, and prawns), rates of polyandry are likely to be variable, but the extent to which patterns of multiple paternity reflect multiple mating, and thus are shaped by postmating processes that bias fertilization toward one or a subset of mated males, is unclear. Here, we use microsatellite markers to examine the frequency of multiple mating (the presence of spermatophores from two or more males) and patterns of paternity in wild populations of western rock lobster (Panulirus cygnus). Our data confirm that >45% of females had attached spermatophores arising from at least two males (i.e., confirming polyandry), but we found very limited evidence for multiple paternity; among 24 clutches sampled in this study, only two arose from fertilizations by two or more males. Single inferred paternal genotypes accounted for all remaining progeny genotypes in each clutch, including several instances when the mother had been shown to mate with two or more males. These findings highlight the need for further work to understand whether polyandry is adaptive and to uncover the mechanisms underlying postmating paternity biases in this system.}, } @article {pmid29760892, year = {2018}, author = {Ponkshe, A and Endler, JA}, title = {Effects of female preference intensity on the permissiveness of sexual trait polymorphisms.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4518-4524}, pmid = {29760892}, issn = {2045-7758}, abstract = {Recent developments in sexual selection theory suggest that on their own, mate preferences can promote the maintenance of sexual trait diversity. However, how mate preferences constrain the permissiveness of sexual trait diversity in different environmental regimes remains an open question. Here, we examine how a range of mate choice parameters affect the permissiveness of sexual trait polymorphism under several selection regimes. We use the null model of sexual selection and show that environments with strong assortative mating significantly increase the permissiveness of sexual trait polymorphism. We show that for a given change in mate choice parameters, the permissiveness of polymorphism changes more in environments with strong natural selection on sexual traits than in environments with weak selection. Sets of nearly stable polymorphic populations with weak assortative mating are more likely to show accidental divergence in sexual traits than sets of populations with strong assortative mating. The permissiveness of sexual trait polymorphism critically depends upon particular combinations of natural selection and mate choice parameters.}, } @article {pmid29760891, year = {2018}, author = {George, R and Gullström, M and Mangora, MM and Mtolera, MSP and Björk, M}, title = {High midday temperature stress has stronger effects on biomass than on photosynthesis: A mesocosm experiment on four tropical seagrass species.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4508-4517}, pmid = {29760891}, issn = {2045-7758}, abstract = {The effect of repeated midday temperature stress on the photosynthetic performance and biomass production of seagrass was studied in a mesocosm setup with four common tropical species, including Thalassia hemprichii, Cymodocea serrulata, Enhalus acoroides, and Thalassodendron ciliatum. To mimic natural conditions during low tides, the plants were exposed to temperature spikes of different maximal temperatures, that is, ambient (29-33°C), 34, 36, 40, and 45°C, during three midday hours for seven consecutive days. At temperatures of up to 36°C, all species could maintain full photosynthetic rates (measured as the electron transport rate, ETR) throughout the experiment without displaying any obvious photosynthetic stress responses (measured as declining maximal quantum yield, Fv/Fm). All species except T. ciliatum could also withstand 40°C, and only at 45°C did all species display significantly lower photosynthetic rates and declining Fv/Fm. Biomass estimation, however, revealed a different pattern, where significant losses of both above- and belowground seagrass biomass occurred in all species at both 40 and 45°C (except for C. serrulata in the 40°C treatment). Biomass losses were clearly higher in the shoots than in the belowground root-rhizome complex. The findings indicate that, although tropical seagrasses presently can cope with high midday temperature stress, a few degrees increase in maximum daily temperature could cause significant losses in seagrass biomass and productivity.}, } @article {pmid29760890, year = {2018}, author = {Slavík, O and Horký, P and Maciak, M and Horká, P and Langrová, I}, title = {Diel movement of brown trout, Salmo trutta, is reduced in dense populations with high site fidelity.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4495-4507}, pmid = {29760890}, issn = {2045-7758}, abstract = {The movement of individuals within preferred areas is reduced by a high availability of food and information about its distribution, while high number of competitors promotes increased movement. Experienced animals use information about social and physical environment to improve resources exploitation, tended to maintain positions within the preferred areas and reuse the environment that is often referred to as site fidelity. In this study, radio-telemetry was used to observe the movements of 98 adult brown trout, Salmo trutta, in oligotrophic streams with different population densities; to determine subpopulation site fidelity, 5,195 conspecifics from 14 subpopulations were individually tagged during spring and autumn. During a 7-year-long field study, we tested the hypothesis that brown trout individuals from subpopulations with high site fidelity would display lower movement. The hypothesis was supported, and reduced movement was further related to high subpopulation density in association with high slope indicating the physical environment-influenced movement. The probability of contact between individuals increased with subpopulation site fidelity and subpopulation density. No influence of food abundance on brown trout movement was found. Furthermore, increased body size predicted higher movement (and vice versa). The least movement occurred during the day and during the full moons. Our study tended to show that individuals reused preferred areas and needed less movement to exploit available resources.}, } @article {pmid29760889, year = {2018}, author = {Denton, JSS and Goolsby, EW}, title = {Measuring inferential importance of taxa using taxon influence indices.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4484-4494}, pmid = {29760889}, issn = {2045-7758}, abstract = {Assessing the importance of different taxa for inferring evolutionary history is a critical, but underutilized, aspect of systematics. Quantifying the importance of all taxa within a dataset provides an empirical measurement that can establish a ranking of extant taxa for ecological study and/or quantify the relative importance of newly announced or redescribed specimens to enable the disentangling of novelty and inferential influence. Here, we illustrate the use of taxon influence indices through analysis of both molecular and morphological datasets, introducing a modified Bayesian approach to the taxon influence index that accounts for model and topological uncertainty. Quantification of taxon influence using the Bayesian approach produced clear rankings for both dataset types. Bayesian taxon rankings differed from maximum likelihood (ML)-derived rankings from a mitogenomic dataset, and the highest ranking taxa exhibited the largest interquartile range in influence estimate, suggesting variance in the estimate must be taken into account when the ranking of taxa is the feature of interest. Application of the Bayesian taxon influence index to a recent morphological analysis of the Tully Monster (Tullimonstrum) reveals that it exhibits consistently low inferential importance across two recent treatments of the taxon with alternative character codings. These results lend support to the idea that taxon influence indices may be robust to character coding and therefore effective for morphological analyses. These results underscore a need for the development of approaches to, and application of, taxon influence analyses both for the purpose of establishing robust rankings for future inquiry and for explicitly quantifying the importance of individual taxa. Quantifying the importance of individual taxa refocuses debates in morphological studies from questions of character choice/significance and taxon sampling to explicitly analytical techniques, and guides discussion of the context of new discoveries.}, } @article {pmid29760888, year = {2018}, author = {Verhaegen, G and McElroy, KE and Bankers, L and Neiman, M and Haase, M}, title = {Adaptive phenotypic plasticity in a clonal invader.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4465-4483}, pmid = {29760888}, issn = {2045-7758}, abstract = {Organisms featuring wide trait variability and occurring in a wide range of habitats, such as the ovoviviparous New Zealand freshwater snail Potamopyrgus antipodarum, are ideal models to study adaptation. Since the mid-19th century, P. antipodarum, characterized by extremely variable shell morphology, has successfully invaded aquatic areas on four continents. Because these obligately and wholly asexual invasive populations harbor low genetic diversity compared to mixed sexual/asexual populations in the native range, we hypothesized that (1) this phenotypic variation in the invasive range might be adaptive with respect to colonization of novel habitats, and (2) that at least some of the variation might be caused by phenotypic plasticity. We surveyed 425 snails from 21 localities across northwest Europe to attempt to disentangle genetic and environmental effects on shell morphology. We analyzed brood size as proxy for fitness and shell geometric morphometrics, while controlling for genetic background. Our survey revealed 10 SNP genotypes nested into two mtDNA haplotypes and indicated that mainly lineage drove variation in shell shape but not size. Physicochemical parameters affected both shell shape and size and the interaction of these traits with brood size. In particular, stronger stream flow rates were associated with larger shells. Our measurements of brood size suggested that relatively larger slender snails with relatively large apertures were better adapted to strong flow than counterparts with broader shells and relatively small apertures. In conclusion, the apparent potential to modify shell morphology plays likely a key role in the invasive success of P. antipodarum; the two main components of shell morphology, namely shape and size, being differentially controlled, the former mainly genetically and the latter predominantly by phenotypic plasticity.}, } @article {pmid29760887, year = {2018}, author = {Gebauer, R and Divíšek, J and Buřič, M and Večeřa, M and Kouba, A and Drozd, B}, title = {Distribution of alien animal species richness in the Czech Republic.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4455-4464}, pmid = {29760887}, issn = {2045-7758}, abstract = {Biogeographical barriers formed by natural forces over billions of years have been substantially disrupted by human activity, particularly in recent centuries. In response to these anthropogenic changes, global homogenization of biota is observed at an ever-increasing rate, causing environmental and economic losses as well as emerging health risks. Identifying factors underlying alien species richness is essential for prevention of future introductions and subsequent spread. In this study, we examined the effects of environmental and human-related factors on distribution of alien animal species richness in the Czech Republic (Central Europe). We compiled a set of maps showing the level of invasion of six categories of alien animal species in each of 628 grid cells (ca. 12.0 × 11.1 km) covering the Czech Republic. Relationships between alien species richness and 12 variables characterizing climatic conditions, topography, land cover, and human population size were calculated using the generalized least squares method. Species richness of all alien species, of invertebrates, and of terrestrial species showed the strongest positive relationship with mean annual temperature, while the number of black and grey (proposed prominent invaders) and aquatic species was most closely related to the presence of large rivers. Alien vertebrates showed a strong negative relationship with annual precipitation. The highest alien animal species richness was found in and near large population centers and in agricultural landscapes in warm and dry lowlands. The gateways for alien aquatic species are rather large rivers over sport fishing and aquaculture import. Compiled maps create a powerful visual communication tool, useful in development of programs to prevent future introductions.}, } @article {pmid29760886, year = {2018}, author = {Wei, X and Yan, L and Zhao, C and Zhang, Y and Xu, Y and Cai, B and Jiang, N and Huang, Y}, title = {Geographic variation in body size and its relationship with environmental gradients in the Oriental Garden Lizard, Calotes versicolor.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4443-4454}, pmid = {29760886}, issn = {2045-7758}, abstract = {Patterns of geographic variation in body size are predicted to evolve as adaptations to local environmental gradients. However, many of these clinal patterns in body size, such as Bergmann's rule, are controversial and require further investigation into ectotherms such as reptiles on a regional scale. To examine the environmental variables (temperature, precipitation, topography and primary productivity) that shaped patterns of geographic variation in body size in the reptile Calotes versicolor, we sampled 180 adult specimens (91 males and 89 females) at 40 locations across the species range in China. The MANOVA results suggest significant sexual size dimorphism in C. versicolor (F23,124 = 11.32, p < .001). Our results showed that C. versicolor failed to fit the Bergmann's rule. We found that the most important predictors of variation in body size of C. versicolor differed for males and females, but mechanisms related to heat balance and water availability hypotheses were involved in both sexes. Temperature seasonality, precipitation of the driest month, precipitation seasonality, and precipitation of the driest quarter were the most important predictors of variation in body size in males, whereas mean precipitation of the warmest quarter, mean temperature of the wettest quarter, precipitation seasonality, and precipitation of the wettest month were most important for body size variation in females. The discrepancy between patterns of association between the sexes suggested that different selection pressures may be acting in males and females.}, } @article {pmid29760885, year = {2018}, author = {Slodowicz, D and Descombes, P and Kikodze, D and Broennimann, O and Müller-Schärer, H}, title = {Areas of high conservation value at risk by plant invaders in Georgia under climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4431-4442}, pmid = {29760885}, issn = {2045-7758}, abstract = {Invasive alien plants (IAP) are a threat to biodiversity worldwide. Understanding and anticipating invasions allow for more efficient management. In this regard, predicting potential invasion risks by IAPs is essential to support conservation planning into areas of high conservation value (AHCV) such as sites exhibiting exceptional botanical richness, assemblage of rare, and threatened and/or endemic plant species. Here, we identified AHCV in Georgia, a country showing high plant richness, and assessed the susceptibility of these areas to colonization by IAPs under present and future climatic conditions. We used actual protected areas and areas of high plant endemism (identified using occurrences of 114 Georgian endemic plant species) as proxies for AHCV. Then, we assessed present and future potential distribution of 27 IAPs using species distribution models under four climate change scenarios and stacked single-species potential distribution into a consensus map representing IAPs richness. We evaluated present and future invasion risks in AHCV using IAPs richness as a metric of susceptibility. We show that the actual protected areas cover only 9.4% of the areas of high plant endemism in Georgia. IAPs are presently located at lower elevations around the large urban centers and in western Georgia. We predict a shift of IAPs toward eastern Georgia and higher altitudes and an increased susceptibility of AHCV to IAPs under future climate change. Our study provides a good baseline for decision makers and stakeholders on where and how resources should be invested in the most efficient way to protect Georgia's high plant richness from IAPs.}, } @article {pmid29760884, year = {2018}, author = {Cavraro, F and Gheno, G and Ganzerla, R and Zucchetta, M and Franzoi, P and Malavasi, S}, title = {Habitat constraints on carotenoid-based coloration in a small euryhaline teleost.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4422-4430}, pmid = {29760884}, issn = {2045-7758}, abstract = {Display of bright and striking color patterns is a widespread way of communication in many animal species. Carotenoid-based coloration accounts for most of the bright yellow, orange, and red displays in invertebrates, fish, amphibians, reptiles, and birds, being widely considered a signal of individual health. This type of coloration is under the influence of several factors, such as sexual selection, predator pressure, pigment availability, and light transmission. Fish offer numerous examples of visual communication by means of color patterns. We used a small cyprinodontid fish, Aphanius fasciatus (Valenciennes, 1821), as a model species to assess habitat constraints on the color display in male caudal fin. Populations from natural and open/closed artificial habitats were tested for differences in the pigmentation of caudal fins. The most important factors explaining the intensity of coloration were the habitat type and the chlorophyll concentration in the sediment, followed by water turbidity; yellow fins were observed in natural habitats with low chlorophyll concentration and high water turbidity, while orange fins occurred in artificial habitats with high chlorophyll concentration and low turbidity. Furthermore, A. fasciatus in artificial habitats showed a higher somatic and a lower reproductive allotment with respect to natural habitats, according to the existing literature on the species. Furthermore, in closed artificial habitats, where the most intense reddish coloration of caudal fins was observed, a trade-off between somatic growth and the coloration intensity of a carotenoid-based sexual ornament has been observed; in these populations, intensity of caudal fin coloration was negatively related to the somatic allotment. Results of this study suggested how both the pigmentation of male's caudal fin and the life history strategies of the species are constrained by habitat characteristics.}, } @article {pmid29760883, year = {2018}, author = {Méndez, V and Wood, JR and Butler, SJ}, title = {Resource diversity and provenance underpin spatial patterns in functional diversity across native and exotic species.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4409-4421}, pmid = {29760883}, issn = {2045-7758}, abstract = {Functional diversity metrics are increasingly used to augment or replace taxonomic diversity metrics to deliver more mechanistic insights into community structure and function. Metrics used to describe landscape structure and characteristics share many of the same limitations as taxonomy-based metrics, particularly their reliance on anthropogenically defined typologies with little consideration of structure, management, or function. However, the development of alternative metrics to describe landscape characteristics has been limited. Here, we extend the functional diversity framework to characterize landscapes based on the diversity of resources available across habitats present. We then examine the influence of resource diversity and provenance on the functional diversities of native and exotic avian communities in New Zealand. Invasive species are increasingly prevalent and considered a global threat to ecosystem function, but the characteristics of and interactions between sympatric native and exotic communities remain unresolved. Understanding their comparative responses to environmental change and the mechanisms underpinning them is of growing importance in predicting community dynamics and changing ecosystem function. We use (i) matrices of resource use (species) and resource availability (habitats) and (ii) occurrence data for 62 native and 25 exotic species and 19 native and 13 exotic habitats in 2015 10 × 10 km quadrats to examine the relationship between native and exotic avian and landscape functional diversity. The numbers of species in, and functional diversities of, native and exotic communities were positively related. Each community displayed evidence of environmental filtering, but it was significantly stronger for exotic species. Less environmental filtering occurred in landscapes providing a more diverse combination of resources, with resource provenance also an influential factor. Landscape functional diversity explained a greater proportion of variance in native and exotic community characteristics than the number of habitat types present. Resource diversity and provenance should be explicitly accounted for when characterizing landscape structure and change as they offer additional mechanistic understanding of the links between environmental filtering and community structure. Manipulating resource diversity through the design and implementation of management actions could prove a powerful tool for the delivery of conservation objectives, be they to protect native species, control exotic species, or maintain ecosystem service provision.}, } @article {pmid29760882, year = {2018}, author = {Kosmala, GK and Brown, GP and Christian, KA and Hudson, CM and Shine, R}, title = {The thermal dependency of locomotor performance evolves rapidly within an invasive species.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4403-4408}, pmid = {29760882}, issn = {2045-7758}, abstract = {Biological invasions can stimulate rapid shifts in organismal performance, via both plasticity and adaptation. We can distinguish between these two proximate mechanisms by rearing offspring from populations under identical conditions and measuring their locomotor abilities in standardized trials. We collected adult cane toads (Rhinella marina) from invasive populations that inhabit regions of Australia with different climatic conditions. We bred those toads and raised their offspring under common-garden conditions before testing their locomotor performance. At high (but not low) temperatures, offspring of individuals from a hotter location (northwestern Australia) outperformed offspring of conspecifics from a cooler location (northeastern Australia). This disparity indicates that, within less than 100 years, thermal performance in cane toads has adapted to the novel abiotic challenges that cane toads have encountered during their invasion of tropical Australia.}, } @article {pmid29760881, year = {2018}, author = {Yu, HJ and Kim, JK}, title = {Upwelling and eddies affect connectivity among local populations of the goldeye rockfish, Sebastes thompsoni (Pisces, Scorpaenoidei).}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4387-4402}, pmid = {29760881}, issn = {2045-7758}, abstract = {The goldeye rockfish, Sebastes thompsoni, commercial rockfish catch in the Northwest Pacific Ocean, may influence its population structure. To clarify the population genetic structure of Korean S. thompsoni and its degree of hybridization with the most close species, Sebastes joyneri, we analyzed a mitochondrial (mt) DNA control region and eleven polymorphic microsatellite (ms) loci. S. joyneri individuals were clearly distinguished from S. thompsoni by the mtDNA control region and ms loci results, with single interspecific hybridization between two species suggesting no impact on genetic structure of S. thompsoni. Analysis of mtDNA revealed no population structure within S. thompsoni, suggesting the survival of a single population in southern refugia during the glacial period. The ms loci results, in contrast, showed two genetically distinct clusters within S. thompsoni: One was predominant throughout Korean coasts (from the Yellow Sea, via the Korea Strait to the East Sea); the other was predominant at Dokdo Island in the East Sea; and both occurred in similar ratios at Wangdolcho Reef in the East Sea. A possible factor that restricts gene flow between Korean coastal and offshore populations in the East Sea may be related to the complex oceanic current patterns such as eddies and upwelling, which represent impermeable barriers to population connectivity for this species. Our findings highlight that these two populations might be representative of two separate stock within Korean waters and maintain their geographically related genetic structure.}, } @article {pmid29760880, year = {2018}, author = {Zhang, G and Li, Q and Sun, S}, title = {Diversity and distribution of parasitic angiosperms in China.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4378-4386}, pmid = {29760880}, issn = {2045-7758}, abstract = {Parasitic plants are an important component of vegetation worldwide, but their diversity and distribution in China have not been systematically reported. This study aimed to (1) explore floral characteristics of China's parasitic plants, (2) map spatial distribution of diversity of these species, and (3) explore factors influencing the distribution pattern. We compiled a nationwide species list of parasitic plants in China, and for each species, we recorded its phylogeny, endemism, and life form (e.g., herb vs. shrub; hemiparasite vs. holoparasite). Species richness and area-corrected species richness were calculated for 28 provinces, covering 98.89% of China's terrestrial area. Regression analyses were performed to determine relationships between provincial area-corrected species richness of parasitic plants and provincial total species richness (including nonparasitic plants) and physical settings (altitude, midlongitude, and midlatitude). A total of 678 species of parasitic angiosperms are recorded in China, 63.13% of which are endemic. Of the total, 59.73% (405 species) are perennials, followed by shrubs/subshrubs (14.75%) and vines (1.47%). About 76.11% (516 species) are of root hemiparasites, higher than that of stem parasites (100, 14.75%), root holoparasites (9.00%), and endophytic parasites (0.15%). A significant positive relationship is found between the area-corrected species richness and the total species richness, which has been previously demonstrated to increase with decreasing longitude and latitude. Moreover, more parasitic species are found in the southwest high-altitude areas than low areas. Consistently, the area-corrected species richness increases with increasing altitude, decreasing latitude, and decreasing longitude, as indicated by regression analyses. China is rich in parasitic flora with a high proportion of endemic species. Perennials and root hemiparasites are the dominant types. The spatial distribution of parasitic plants is largely heterogeneous, with more species living in southwest China, similar to the distribution pattern of Chinese angiosperms. The positive relationship between parasitic and nonparasitic plant species richness should be addressed in the future.}, } @article {pmid29760879, year = {2018}, author = {Vautz, W and Hariharan, C and Weigend, M}, title = {Smell the change: On the potential of gas-chromatographic ion mobility spectrometry in ecosystem monitoring.}, journal = {Ecology and evolution}, volume = {8}, number = {9}, pages = {4370-4377}, pmid = {29760879}, issn = {2045-7758}, abstract = {Plant volatile organic compounds (pVOCs) are being recognized as an important factor in plant-environment interactions. Both the type and amount of the emissions appear to be heavily affected by climate change. A range of studies therefore has been directed toward understanding pVOC emissions, mostly under laboratory conditions (branch/leaf enclosure). However, there is a lack of rapid, sensitive, and selective analytical methods, and therefore, only little is known about VOC emissions under natural, outdoor conditions. An increased sensitivity and the identification of taxon-specific patterns could turn VOC analysis into a powerful tool for the monitoring of atmospheric chemistry, ecosystems, and biodiversity, with far-reaching relevance to the impact of climate change on pVOCs and vice versa. This study for the first time investigates the potential of ion mobility spectrometry coupled to gas-chromatographic preseparation (GC-IMS) to dramatically increase sensitivity and selectivity for continuous monitoring of pVOCs and to discriminate contributing plant taxa and their phenology. Leaf volatiles were analyzed for nine different common herbaceous plants from Germany. Each plant turned out to have a characteristic metabolite pattern. pVOC patterns in the field would thus reflect the composition of the vegetation, but also phenology (with herbaceous and deciduous plants contributing according to season). The technique investigated here simultaneously enables the identification and quantification of substances characteristic for environmental pollution such as industrial and traffic emissions or pesticides. GC-IMS thus has an enormous potential to provide a broad range of data on ecosystem function. This approach with near-continues measurements in the real plant communities could provide crucial insights on pVOC-level emissions and their relation to climate and phenology and thus provide a sound basis for modeling climate change scenarios including pVOC emissions.}, } @article {pmid29760866, year = {2018}, author = {Bernal-Bayard, J and Gomez-Valero, L and Wessel, A and Khanna, V and Bouchier, C and Ghigo, JM}, title = {Short genome report of cellulose-producing commensal Escherichia coli 1094.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {13}, pmid = {29760866}, issn = {1944-3277}, abstract = {Bacterial surface colonization and biofilm formation often rely on the production of an extracellular polymeric matrix that mediates cell-cell and cell-surface contacts. In Escherichia coli and many Betaproteobacteria and Gammaproteobacteria cellulose is often the main component of the extracellular matrix. Here we report the complete genome sequence of the cellulose producing strain E. coli 1094 and compare it with five other closely related genomes within E. coli phylogenetic group A. We present a comparative analysis of the regions encoding genes responsible for cellulose biosynthesis and discuss the changes that could have led to the loss of this important adaptive advantage in several E. coli strains. Data deposition: The annotated genome sequence has been deposited at the European Nucleotide Archive under the accession number PRJEB21000.}, } @article {pmid29760496, year = {2018}, author = {}, title = {An unexpected twist in 'crystallized' time.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {283}, doi = {10.1038/d41586-018-05170-5}, pmid = {29760496}, issn = {1476-4687}, } @article {pmid29760495, year = {2018}, author = {}, title = {A map for fatal brain tumour may aid cures.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {283}, doi = {10.1038/d41586-018-05168-z}, pmid = {29760495}, issn = {1476-4687}, } @article {pmid29760492, year = {2018}, author = {}, title = {DNA points to a frog-killer's birthplace.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {283}, doi = {10.1038/d41586-018-05138-5}, pmid = {29760492}, issn = {1476-4687}, } @article {pmid29760491, year = {2018}, author = {}, title = {Flesh-eating bacteria thrive on pain.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {283}, doi = {10.1038/d41586-018-05137-6}, pmid = {29760491}, issn = {1476-4687}, } @article {pmid29760490, year = {2018}, author = {}, title = {Bloody battles as birds maul European bats.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {282}, doi = {10.1038/d41586-018-05128-7}, pmid = {29760490}, issn = {1476-4687}, mesh = {Animals ; *Birds ; *Chiroptera ; *Endangered Species ; Introduced Species ; Population Dynamics ; *Predatory Behavior ; Spain ; }, } @article {pmid29760489, year = {2018}, author = {}, title = {Gymnastic feats help DNA 'walker' set speed record.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {283}, doi = {10.1038/d41586-018-05127-8}, pmid = {29760489}, issn = {1476-4687}, } @article {pmid29760488, year = {2018}, author = {}, title = {Mutant mice hold back the years.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {282}, doi = {10.1038/d41586-018-05125-w}, pmid = {29760488}, issn = {1476-4687}, mesh = {Aging/*genetics ; Animals ; CCAAT-Enhancer-Binding Protein-beta/deficiency/*genetics/metabolism ; Female ; Immune System/metabolism ; Longevity/*genetics ; Male ; Metabolism/genetics ; Mice ; Neoplasms/genetics ; Weight Gain/genetics ; }, } @article {pmid29760487, year = {2018}, author = {}, title = {Holiday trips spell trouble for the future of life on Earth.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {282-283}, doi = {10.1038/d41586-018-05108-x}, pmid = {29760487}, issn = {1476-4687}, mesh = {Carbon Footprint/*statistics & numerical data ; Earth (Planet) ; Greenhouse Effect/*statistics & numerical data ; Holidays/*statistics & numerical data ; Life ; Travel/*statistics & numerical data/*trends ; }, } @article {pmid29760486, year = {2018}, author = {}, title = {Long-lost data reveal astronauts' mark on the Moon.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {282}, doi = {10.1038/d41586-018-05107-y}, pmid = {29760486}, issn = {1476-4687}, } @article {pmid29760468, year = {2018}, author = {Peng, J and Cao, D and He, Z and Guo, J and Hapala, P and Ma, R and Cheng, B and Chen, J and Xie, WJ and Li, XZ and Jelínek, P and Xu, LM and Gao, YQ and Wang, EG and Jiang, Y}, title = {The effect of hydration number on the interfacial transport of sodium ions.}, journal = {Nature}, volume = {557}, number = {7707}, pages = {701-705}, doi = {10.1038/s41586-018-0122-2}, pmid = {29760468}, issn = {1476-4687}, abstract = {Ion hydration and transport at interfaces are relevant to a wide range of applied fields and natural processes1-5. Interfacial effects are particularly profound in confined geometries such as nanometre-sized channels6-8, where the mechanisms of ion transport in bulk solutions may not apply9,10. To correlate atomic structure with the transport properties of hydrated ions, both the interfacial inhomogeneity and the complex competing interactions among ions, water and surfaces require detailed molecular-level characterization. Here we constructed individual sodium ion (Na+) hydrates on a NaCl(001) surface by progressively attaching single water molecules (one to five) to the Na+ ion using a combined scanning tunnelling microscopy and noncontact atomic force microscopy system. We found that the Na+ ion hydrated with three water molecules diffuses orders of magnitude more quickly than other ion hydrates. Ab initio calculations revealed that such high ion mobility arises from the existence of a metastable state, in which the three water molecules around the Na+ ion can rotate collectively with a rather small energy barrier. This scenario would apply even at room temperature according to our classical molecular dynamics simulations. Our work suggests that anomalously high diffusion rates for specific hydration numbers of ions are generally determined by the degree of symmetry match between the hydrates and the surface lattice.}, } @article {pmid29760463, year = {2018}, author = {Jay, ZJ and Beam, JP and Dlakić, M and Rusch, DB and Kozubal, MA and Inskeep, WP}, title = {Marsarchaeota are an aerobic archaeal lineage abundant in geothermal iron oxide microbial mats.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {732-740}, doi = {10.1038/s41564-018-0163-1}, pmid = {29760463}, issn = {2058-5276}, abstract = {The discovery of archaeal lineages is critical to our understanding of the universal tree of life and evolutionary history of the Earth. Geochemically diverse thermal environments in Yellowstone National Park provide unprecedented opportunities for studying archaea in habitats that may represent analogues of early Earth. Here, we report the discovery and characterization of a phylum-level archaeal lineage proposed and herein referred to as the 'Marsarchaeota', after the red planet. The Marsarchaeota contains at least two major subgroups prevalent in acidic, microaerobic geothermal Fe(III) oxide microbial mats across a temperature range from ~50-80 °C. Metagenomics, single-cell sequencing, enrichment culturing and in situ transcriptional analyses reveal their biogeochemical role as facultative aerobic chemoorganotrophs that may also mediate the reduction of Fe(III). Phylogenomic analyses of replicate assemblies corresponding to two groups of Marsarchaeota indicate that they branch between the Crenarchaeota and all other major archaeal lineages. Transcriptomic analyses of several Fe(III) oxide mat communities reveal that these organisms were actively transcribing two different terminal oxidase complexes in situ and genes comprising an F420-dependent butanal catabolism. The broad distribution of Marsarchaeota in geothermal, microaerobic Fe(III) oxide mats suggests that similar habitat types probably played an important role in the evolution of archaea.}, } @article {pmid29760462, year = {2018}, author = {Iyer, S and Le, D and Park, BR and Kim, M}, title = {Distinct mechanisms coordinate transcription and translation under carbon and nitrogen starvation in Escherichia coli.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {741-748}, doi = {10.1038/s41564-018-0161-3}, pmid = {29760462}, issn = {2058-5276}, abstract = {Bacteria adapt to environmental stress by producing proteins that provide stress protection. However, stress can severely perturb the kinetics of gene expression, disrupting protein production. Here, we characterized how Escherichia coli mitigates such perturbations under nutrient stress through the kinetic coordination of transcription and translation. We observed that, when translation became limiting under nitrogen starvation, transcription elongation slowed accordingly. This slowdown was mediated by (p)ppGpp, the alarmone whose primary role is thought to be promoter regulation. This kinetic coordination by (p)ppGpp was critical for the robust synthesis of gene products. Surprisingly, under carbon starvation, (p)ppGpp was dispensable for robust synthesis. Characterization of the underlying kinetics revealed that under carbon starvation, transcription became limiting, and translation aided transcription elongation. This mechanism naturally coordinated transcription with translation, alleviating the need for (p)ppGpp as a mediator. These contrasting mechanisms for coordination resulted in the condition-dependent effects of (p)ppGpp on global protein synthesis and starvation survival. Our findings reveal a kinetic aspect of gene expression plasticity, establishing (p)ppGpp as a condition-dependent global effector of gene expression.}, } @article {pmid29760441, year = {2018}, author = {Salazar, D and Lokvam, J and Mesones, I and Vásquez Pilco, M and Ayarza Zuñiga, JM and de Valpine, P and Fine, PVA}, title = {Origin and maintenance of chemical diversity in a species-rich tropical tree lineage.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {983-990}, doi = {10.1038/s41559-018-0552-0}, pmid = {29760441}, issn = {2397-334X}, abstract = {Plant secondary metabolites play important ecological and evolutionary roles, most notably in the deterrence of natural enemies. The classical theory explaining the evolution of plant chemical diversity is that new defences arise through a pairwise co-evolutionary arms race between plants and their specialized natural enemies. However, plant species are bombarded by dozens of different herbivore taxa from disparate phylogenetic lineages that span a wide range of feeding strategies and have distinctive physiological constraints that interact differently with particular plant metabolites. How do plant defence chemicals evolve under such multiple and potentially contrasting selective pressures imposed by diverse herbivore communities? To tackle this question, we exhaustively characterized the chemical diversity and insect herbivore fauna from 31 sympatric species of Amazonian Protieae (Burseraceae) trees. Using a combination of phylogenetic, metabolomic and statistical learning tools, we show that secondary metabolites that were associated with repelling herbivores (1) were more frequent across the Protieae phylogeny and (2) were found in average higher abundance than other compounds. Our findings suggest that generalist herbivores can play an important role in shaping plant chemical diversity and support the hypothesis that chemical diversity can also arise from the cumulative outcome of multiple diffuse interactions.}, } @article {pmid29760440, year = {2018}, author = {Schweiger, AK and Cavender-Bares, J and Townsend, PA and Hobbie, SE and Madritch, MD and Wang, R and Tilman, D and Gamon, JA}, title = {Plant spectral diversity integrates functional and phylogenetic components of biodiversity and predicts ecosystem function.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {976-982}, doi = {10.1038/s41559-018-0551-1}, pmid = {29760440}, issn = {2397-334X}, abstract = {Biodiversity promotes ecosystem function as a consequence of functional differences among organisms that enable resource partitioning and facilitation. As the need for biodiversity assessments increases in the face of accelerated global change, novel approaches that are rapid, repeatable and scalable are critical, especially in ecosystems for which information about species identity and the number of species is difficult to acquire. Here, we present 'spectral diversity'-a spectroscopic index of the variability of electromagnetic radiation reflected from plants measured in the visible, near-infrared and short-wave infrared regions (400-2,400 nm). Using data collected from the Cedar Creek biodiversity experiment (Minnesota, USA), we provide evidence that the dissimilarity of species' leaf spectra increases with functional dissimilarity and evolutionary divergence time. Spectral diversity at the leaf level explains 51% of total variation in productivity-a proportion comparable to taxonomic (47%), functional (51%) or phylogenetic diversity (48%)-and performs similarly when calculated from high-resolution canopy image spectra. Spectral diversity is an emerging dimension of plant biodiversity that integrates trait variation within and across species even in the absence of taxonomic, functional, phylogenetic or abundance information, and has the potential to transform biodiversity assessment because of its scalability to remote sensing.}, } @article {pmid29760439, year = {2018}, author = {Deplazes-Zemp, A and Abiven, S and Schaber, P and Schaepman, M and Schaepman-Strub, G and Schmid, B and Shimizu, KK and Altermatt, F}, title = {The Nagoya Protocol could backfire on the Global South.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {917-919}, doi = {10.1038/s41559-018-0561-z}, pmid = {29760439}, issn = {2397-334X}, } @article {pmid29760105, year = {2018}, author = {Heikkilä, K and Van Beijsterveldt, CEM and Haukka, J and Iivanainen, M and Saari-Kemppainen, A and Silventoinen, K and Boomsma, DI and Yokoyama, Y and Vuoksimaa, E}, title = {Triplets, birthweight, and handedness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6076-6081}, pmid = {29760105}, issn = {1091-6490}, mesh = {Birth Weight/physiology ; Female ; Functional Laterality/*physiology ; Gestational Age ; Humans ; Infant ; Infant, Low Birth Weight/*physiology ; Infant, Newborn ; Japan ; Male ; Netherlands ; Pregnancy ; Pregnancy, Multiple/physiology ; Premature Birth ; Prevalence ; Risk Factors ; Triplets ; }, abstract = {The mechanisms behind handedness formation in humans are still poorly understood. Very low birthweight is associated with higher odds of left-handedness, but whether this is due to low birthweight itself or premature birth is unknown. Handedness has also been linked to development, but the role of birthweight behind this association is unclear. Knowing that birthweight is lower in multiple births, triplets being about 1.5 kg lighter in comparison with singletons, and that multiples have a higher prevalence of left-handedness than singletons, we studied the association between birthweight and handedness in two large samples consisting exclusively of triplets from Japan (n = 1,305) and the Netherlands (n = 947). In both samples, left-handers had significantly lower birthweight (Japanese mean = 1,599 g [95% confidence interval (CI): 1,526-1,672 g]; Dutch mean = 1,794 g [95% CI: 1,709-1,879 g]) compared with right-handers (Japanese mean = 1,727 g [95% CI: 1,699-1,755 g]; Dutch mean = 1,903 g [95% CI: 1,867-1,938 g]). Within-family and between-family analyses both suggested that left-handedness is associated with lower birthweight, also when fully controlling for gestational age. Left-handers also had significantly delayed motor development and smaller infant head circumference compared with right-handers, but these associations diluted and became nonsignificant when controlling for birthweight. Our study in triplets provides evidence for the link between low birthweight and left-handedness. Our results also suggest that developmental differences between left- and right-handers are due to a shared etiology associated with low birthweight.}, } @article {pmid29760104, year = {2018}, author = {}, title = {Correction for Xu et al., Drought delays development of the sorghum root microbiome and enriches for monoderm bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4952}, doi = {10.1073/pnas.1807275115}, pmid = {29760104}, issn = {1091-6490}, } @article {pmid29760103, year = {2018}, author = {Hughes, LC and Ortí, G and Huang, Y and Sun, Y and Baldwin, CC and Thompson, AW and Arcila, D and Betancur-R, R and Li, C and Becker, L and Bellora, N and Zhao, X and Li, X and Wang, M and Fang, C and Xie, B and Zhou, Z and Huang, H and Chen, S and Venkatesh, B and Shi, Q}, title = {Comprehensive phylogeny of ray-finned fishes (Actinopterygii) based on transcriptomic and genomic data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6249-6254}, doi = {10.1073/pnas.1719358115}, pmid = {29760103}, issn = {1091-6490}, mesh = {Animals ; Evolution, Molecular ; Exons/genetics ; Fishes/*genetics ; Fossils ; Gene Duplication/genetics ; Genome/*genetics ; Genomics/methods ; Models, Genetic ; Phylogeny ; Transcriptome/*genetics ; }, abstract = {Our understanding of phylogenetic relationships among bony fishes has been transformed by analysis of a small number of genes, but uncertainty remains around critical nodes. Genome-scale inferences so far have sampled a limited number of taxa and genes. Here we leveraged 144 genomes and 159 transcriptomes to investigate fish evolution with an unparalleled scale of data: >0.5 Mb from 1,105 orthologous exon sequences from 303 species, representing 66 out of 72 ray-finned fish orders. We apply phylogenetic tests designed to trace the effect of whole-genome duplication events on gene trees and find paralogy-free loci using a bioinformatics approach. Genome-wide data support the structure of the fish phylogeny, and hypothesis-testing procedures appropriate for phylogenomic datasets using explicit gene genealogy interrogation settle some long-standing uncertainties, such as the branching order at the base of the teleosts and among early euteleosts, and the sister lineage to the acanthomorph and percomorph radiations. Comprehensive fossil calibrations date the origin of all major fish lineages before the end of the Cretaceous.}, } @article {pmid29760102, year = {2018}, author = {Li, W and Hulswit, RJG and Kenney, SP and Widjaja, I and Jung, K and Alhamo, MA and van Dieren, B and van Kuppeveld, FJM and Saif, LJ and Bosch, BJ}, title = {Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5135-E5143}, pmid = {29760102}, issn = {1091-6490}, mesh = {Animals ; Antibodies, Viral/immunology ; CD13 Antigens/metabolism ; Cats ; Cell Line ; Cercopithecus aethiops ; Chickens ; *Communicable Diseases, Emerging/transmission/veterinary/virology ; Coronavirus/immunology/*pathogenicity/*physiology ; *Coronavirus Infections/transmission/veterinary/virology ; Dogs ; Host Specificity ; Host-Pathogen Interactions/*physiology ; Humans ; Madin Darby Canine Kidney Cells ; Mice ; Spike Glycoprotein, Coronavirus/chemistry/genetics/metabolism ; Swine ; Vero Cells ; Zoonoses/transmission/virology ; }, abstract = {Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the Alphacoronavirus genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.}, } @article {pmid29760101, year = {2018}, author = {Schmidt, K and Gardill, BR and Kern, A and Kirchweger, P and Börsch, M and Muller, YA}, title = {Design of an allosterically modulated doxycycline and doxorubicin drug-binding protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5744-5749}, pmid = {29760101}, issn = {1091-6490}, mesh = {Allosteric Site/genetics ; Doxorubicin/chemistry/*metabolism ; Doxycycline/chemistry/*metabolism ; Drug Carriers/chemistry/metabolism ; Humans ; Models, Molecular ; Protein Engineering/*methods ; *Recombinant Proteins/chemistry/genetics/metabolism ; alpha 1-Antichymotrypsin/chemistry/genetics/metabolism ; }, abstract = {The allosteric interplay between distant functional sites present in a single protein provides for one of the most important regulatory mechanisms in biological systems. While the design of ligand-binding sites into proteins remains challenging, this holds even truer for the coupling of a newly engineered binding site to an allosteric mechanism that regulates the ligand affinity. Here it is shown how computational design algorithms enabled the introduction of doxycycline- and doxorubicin-binding sites into the serine proteinase inhibitor (serpin) family member α1-antichymotrypsin. Further engineering allowed exploitation of the proteinase-triggered serpin-typical S-to-R transition to modulate the ligand affinities. These design variants follow strategies observed in naturally occurring plasma globulins that allow for the targeted delivery of hormones in the blood. By analogy, we propose that the variants described in the present study could be further developed to allow for the delivery of the antibiotic doxycycline and the anticancer compound doxorubicin to tissues/locations that express specific proteinases, such as bacterial infection sites or tumor cells secreting matrix metalloproteinases.}, } @article {pmid29760100, year = {2018}, author = {Zhang, QF and Li, H and Chen, M and Guo, A and Wen, Y and Poo, MM}, title = {Functional organization of intrinsic and feedback presynaptic inputs in the primary visual cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5174-E5182}, pmid = {29760100}, issn = {1091-6490}, mesh = {Animals ; Axons/physiology ; Calcium/metabolism ; Feedback, Physiological/physiology ; Mice ; Molecular Imaging ; Presynaptic Terminals/*physiology ; Visual Cortex/diagnostic imaging/*physiology ; Visual Pathways/diagnostic imaging/*physiology ; }, abstract = {In the primary visual cortex (V1) of many mammalian species, neurons are spatially organized according to their preferred orientation into a highly ordered map. However, whether and how the various presynaptic inputs to V1 neurons are organized relative to the neuronal orientation map remain unclear. To address this issue, we constructed genetically encoded calcium indicators targeting axon boutons in two colors and used them to map the organization of axon boutons of V1 intrinsic and V2-V1 feedback projections in tree shrews. Both connections are spatially organized into maps according to the preferred orientations of axon boutons. Dual-color calcium imaging showed that V1 intrinsic inputs are precisely aligned to the orientation map of V1 cell bodies, while the V2-V1 feedback projections are aligned to the V1 map with less accuracy. Nonselective integration of intrinsic presynaptic inputs around the dendritic tree is sufficient to reproduce cell body orientation preference. These results indicate that a precisely aligned map of intrinsic inputs could reinforce the neuronal map in V1, a principle that may be prevalent for brain areas with function maps.}, } @article {pmid29760099, year = {2018}, author = {Johnson, CT and Wroe, JA and Agarwal, R and Martin, KE and Guldberg, RE and Donlan, RM and Westblade, LF and García, AJ}, title = {Hydrogel delivery of lysostaphin eliminates orthopedic implant infection by Staphylococcus aureus and supports fracture healing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4960-E4969}, pmid = {29760099}, issn = {1091-6490}, support = {F30 AR069472/AR/NIAMS NIH HHS/United States ; R01 AR062920/AR/NIAMS NIH HHS/United States ; T32 GM008169/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/*administration & dosage/pharmacology/therapeutic use ; Biocompatible Materials/therapeutic use ; Disease Models, Animal ; Femoral Fractures/surgery ; Fracture Healing/*drug effects ; Hydrogels/*therapeutic use ; Lysostaphin/*administration & dosage/pharmacology/therapeutic use ; Male ; Mice ; Mice, Inbred C57BL ; Prosthesis Design ; *Prosthesis-Related Infections/drug therapy/prevention & control ; *Staphylococcal Infections/drug therapy/prevention & control ; Staphylococcus aureus ; }, abstract = {Orthopedic implant infections are a significant clinical problem, with current therapies limited to surgical debridement and systemic antibiotic regimens. Lysostaphin is a bacteriolytic enzyme with high antistaphylococcal activity. We engineered a lysostaphin-delivering injectable PEG hydrogel to treat Staphylococcus aureus infections in bone fractures. The injectable hydrogel formulation adheres to exposed tissue and fracture surfaces, ensuring efficient, local delivery of lysostaphin. Lysostaphin encapsulation within this synthetic hydrogel maintained enzyme stability and activity. Lysostaphin-delivering hydrogels exhibited enhanced antibiofilm activity compared with soluble lysostaphin. Lysostaphin-delivering hydrogels eradicated S. aureus infection and outperformed prophylactic antibiotic and soluble lysostaphin therapy in a murine model of femur fracture. Analysis of the local inflammatory response to infections treated with lysostaphin-delivering hydrogels revealed indistinguishable differences in cytokine secretion profiles compared with uninfected fractures, demonstrating clearance of bacteria and associated inflammation. Importantly, infected fractures treated with lysostaphin-delivering hydrogels fully healed by 5 wk with bone formation and mechanical properties equivalent to those of uninfected fractures, whereas fractures treated without the hydrogel carrier were equivalent to untreated infections. Finally, lysostaphin-delivering hydrogels eliminate methicillin-resistant S. aureus infections, supporting this therapy as an alternative to antibiotics. These results indicate that lysostaphin-delivering hydrogels effectively eliminate orthopedic S. aureus infections while simultaneously supporting fracture repair.}, } @article {pmid29760098, year = {2018}, author = {Motallebzadeh, H and Soons, JAM and Puria, S}, title = {Cochlear amplification and tuning depend on the cellular arrangement within the organ of Corti.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5762-5767}, pmid = {29760098}, issn = {1091-6490}, support = {R01 DC007910/DC/NIDCD NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Animals ; Cochlea/anatomy & histology/physiology ; *Computer Simulation ; Finite Element Analysis ; Mice ; *Models, Biological ; *Organ of Corti/anatomy & histology/cytology/physiology ; }, abstract = {The field of cochlear mechanics has been undergoing a revolution due to recent findings made possible by advancements in measurement techniques. While it has long been assumed that basilar-membrane (BM) motion is the most important determinant of sound transduction by the inner hair cells (IHCs), it turns out that other parts of the sensory epithelium closer to the IHCs, such as the reticular lamina (RL), move with significantly greater amplitude for weaker sounds. It has not been established how these findings are related to the complex cytoarchitecture of the organ of Corti between the BM and RL, which is composed of a lattice of asymmetric Y-shaped elements, each consisting of a basally slanted outer hair cell (OHC), an apically slanted phalangeal process (PhP), and a supporting Deiters' cell (DC). Here, a computational model of the mouse cochlea supports the hypothesis that the OHC micromotors require this Y-shaped geometry for their contribution to the exquisite sensitivity and frequency selectivity of the mammalian cochlea. By varying only the OHC gain parameter, the model can reproduce measurements of BM and RL gain and tuning for a variety of input sound levels. Malformations such as reversing the orientations of the OHCs and PhPs or removing the PhPs altogether greatly reduce the effectiveness of the OHC motors. These results imply that the DCs and PhPs must be properly accounted for in emerging OHC regeneration therapies.}, } @article {pmid29760097, year = {2018}, author = {Dasgupta, R and Miettinen, MS and Fricke, N and Lipowsky, R and Dimova, R}, title = {The glycolipid GM1 reshapes asymmetric biomembranes and giant vesicles by curvature generation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5756-5761}, pmid = {29760097}, issn = {1091-6490}, mesh = {Biotechnology/*methods ; Electroporation ; G(M1) Ganglioside/*chemistry/*metabolism ; Lipids ; *Membranes, Artificial ; Molecular Dynamics Simulation ; Nanotubes/*chemistry ; }, abstract = {The ganglioside GM1 is present in neuronal membranes at elevated concentrations with an asymmetric spatial distribution. It is known to generate curvature and can be expected to strongly influence the neuron morphology. To elucidate these effects, we prepared giant vesicles with GM1 predominantly present in one leaflet of the membrane, mimicking the asymmetric GM1 distribution in neuronal membranes. Based on pulling inward and outward tubes, we developed a technique that allowed the direct measurement of the membrane spontaneous curvature. Using vesicle electroporation and fluorescence intensity analysis, we were able to quantify the GM1 asymmetry across the membrane and to subsequently estimate the local curvature generated by the molecule in the bilayer. Molecular-dynamics simulations confirm the experimentally determined dependence of the membrane spontaneous curvature as a function of GM1 asymmetry. GM1 plays a crucial role in connection with receptor proteins. Our results on curvature generation of GM1 point to an additional important role of this ganglioside, namely in shaping neuronal membranes.}, } @article {pmid29760096, year = {2018}, author = {Pan, CJ and Yuan, C and Zhu, G and Zhang, Q and Huang, CJ and Lin, MC and Angell, M and Hwang, BJ and Kaghazchi, P and Dai, H}, title = {An operando X-ray diffraction study of chloroaluminate anion-graphite intercalation in aluminum batteries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5670-5675}, pmid = {29760096}, issn = {1091-6490}, abstract = {We investigated rechargeable aluminum (Al) batteries composed of an Al negative electrode, a graphite positive electrode, and an ionic liquid (IL) electrolyte at temperatures down to -40 °C. The reversible battery discharge capacity at low temperatures could be superior to that at room temperature. In situ/operando electrochemical and synchrotron X-ray diffraction experiments combined with theoretical modeling revealed stable AlCl4-/graphite intercalation up to stage 3 at low temperatures, whereas intercalation was reversible up to stage 4 at room temperature (RT). The higher-degree anion/graphite intercalation at low temperatures affords rechargeable Al battery with higher discharge voltage (up to 2.5 V, a record for Al battery) and energy density. A remarkable cycle life of >20,000 cycles at a rate of 6C (10 minutes charge time) was achievable for Al battery operating at low temperatures, corresponding to a >50-year battery life if charged/discharged once daily.}, } @article {pmid29760095, year = {2018}, author = {De Moraes, CM and Wanjiku, C and Stanczyk, NM and Pulido, H and Sims, JW and Betz, HS and Read, AF and Torto, B and Mescher, MC}, title = {Volatile biomarkers of symptomatic and asymptomatic malaria infection in humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5780-5785}, pmid = {29760095}, issn = {1091-6490}, mesh = {Animals ; Biomarkers/*analysis/metabolism ; Child ; Discriminant Analysis ; Humans ; Kenya ; Machine Learning ; Malaria/*diagnosis/metabolism ; Models, Statistical ; Predictive Value of Tests ; Skin/*metabolism ; Volatile Organic Compounds/*analysis/metabolism ; }, abstract = {Malaria remains among the world's deadliest diseases, and control efforts depend critically on the availability of effective diagnostic tools, particularly for the identification of asymptomatic infections, which play a key role in disease persistence and may account for most instances of transmission but often evade detection by current screening methods. Research on humans and in animal models has shown that infection by malaria parasites elicits changes in host odors that influence vector attraction, suggesting that such changes might yield robust biomarkers of infection status. Here we present findings based on extensive collections of skin volatiles from human populations with high rates of malaria infection in Kenya. We report broad and consistent effects of malaria infection on human volatile profiles, as well as significant divergence in the effects of symptomatic and asymptomatic infections. Furthermore, predictive models based on machine learning algorithms reliably determined infection status based on volatile biomarkers. Critically, our models identified asymptomatic infections with 100% sensitivity, even in the case of low-level infections not detectable by microscopy, far exceeding the performance of currently available rapid diagnostic tests in this regard. We also identified a set of individual compounds that emerged as consistently important predictors of infection status. These findings suggest that volatile biomarkers may have significant potential for the development of a robust, noninvasive screening method for detecting malaria infections under field conditions.}, } @article {pmid29760094, year = {2018}, author = {Lai, YS and Renna, L and Yarema, J and Ruberti, C and He, SY and Brandizzi, F}, title = {Salicylic acid-independent role of NPR1 is required for protection from proteotoxic stress in the plant endoplasmic reticulum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5203-E5212}, pmid = {29760094}, issn = {1091-6490}, support = {R01 GM101038/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/genetics/metabolism/physiology ; Arabidopsis Proteins/genetics/*metabolism ; Basic-Leucine Zipper Transcription Factors/genetics/metabolism ; Endoplasmic Reticulum/genetics/*metabolism ; Endoplasmic Reticulum Stress/*physiology ; Salicylic Acid/metabolism ; Unfolded Protein Response/*physiology ; }, abstract = {The unfolded protein response (UPR) is an ancient signaling pathway designed to protect cells from the accumulation of unfolded and misfolded proteins in the endoplasmic reticulum (ER). Because misregulation of the UPR is potentially lethal, a stringent surveillance signaling system must be in place to modulate the UPR. The major signaling arms of the plant UPR have been discovered and rely on the transcriptional activity of the transcription factors bZIP60 and bZIP28 and on the kinase and ribonuclease activity of IRE1, which splices mRNA to activate bZIP60. Both bZIP28 and bZIP60 modulate UPR gene expression to overcome ER stress. In this study, we demonstrate at a genetic level that the transcriptional role of bZIP28 and bZIP60 in ER-stress responses is antagonized by nonexpressor of PR1 genes 1 (NPR1), a critical redox-regulated master regulator of salicylic acid (SA)-dependent responses to pathogens, independently of its role in SA defense. We also establish that the function of NPR1 in the UPR is concomitant with ER stress-induced reduction of the cytosol and translocation of NPR1 to the nucleus where it interacts with bZIP28 and bZIP60. Our results support a cellular role for NPR1 as well as a model for plant UPR regulation whereby SA-independent ER stress-induced redox activation of NPR1 suppresses the transcriptional role of bZIP28 and bZIP60 in the UPR.}, } @article {pmid29760093, year = {2018}, author = {Springer, AM and van Vliet, GB and Bool, N and Crowley, M and Fullagar, P and Lea, MA and Monash, R and Price, C and Vertigan, C and Woehler, EJ}, title = {Transhemispheric ecosystem disservices of pink salmon in a Pacific Ocean macrosystem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5038-E5045}, pmid = {29760093}, issn = {1091-6490}, mesh = {Animal Migration ; Animals ; Birds/*physiology ; Clutch Size ; Ecology ; *Ecosystem ; Environmental Monitoring ; Food Chain ; Marine Biology ; Pacific Ocean ; Salmon/*physiology ; Temperature ; }, abstract = {Pink salmon (Oncorhynchus gorbuscha) in the North Pacific Ocean have flourished since the 1970s, with growth in wild populations augmented by rising hatchery production. As their abundance has grown, so too has evidence that they are having important effects on other species and on ocean ecosystems. In alternating years of high abundance, they can initiate pelagic trophic cascades in the northern North Pacific Ocean and Bering Sea and depress the availability of common prey resources of other species of salmon, resident seabirds, and other pelagic species. We now propose that the geographic scale of ecosystem disservices of pink salmon is far greater due to a 15,000-kilometer transhemispheric teleconnection in a Pacific Ocean macrosystem maintained by short-tailed shearwaters (Ardenna tenuirostris), seabirds that migrate annually between their nesting grounds in the South Pacific Ocean and wintering grounds in the North Pacific Ocean. Over this century, the frequency and magnitude of mass mortalities of shearwaters as they arrive in Australia, and their abundance and productivity, have been related to the abundance of pink salmon. This has influenced human social, economic, and cultural traditions there, and has the potential to alter the role shearwaters play in insular terrestrial ecology. We can view the unique biennial pulses of pink salmon as a large, replicated, natural experiment that offers basin-scale opportunities to better learn how these ecosystems function. By exploring trophic interaction chains driven by pink salmon, we may achieve a deeper conservation conscientiousness for these northern open oceans.}, } @article {pmid29760092, year = {2018}, author = {Ban, Z and Qin, H and Mitchell, AJ and Liu, B and Zhang, F and Weng, JK and Dixon, RA and Wang, G}, title = {Noncatalytic chalcone isomerase-fold proteins in Humulus lupulus are auxiliary components in prenylated flavonoid biosynthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5223-E5232}, pmid = {29760092}, issn = {1091-6490}, mesh = {Acyltransferases/chemistry/metabolism ; Flavonoids/*biosynthesis ; Flowers/metabolism ; Humulus/*enzymology/genetics ; *Intramolecular Lyases/chemistry/genetics/metabolism ; Metabolic Networks and Pathways/genetics ; Mutation/genetics ; *Plant Proteins/chemistry/genetics/metabolism ; Prenylation/*genetics ; Sequence Analysis, DNA ; }, abstract = {Xanthohumol (XN) and demethylxanthohumol (DMX) are specialized prenylated chalconoids with multiple pharmaceutical applications that accumulate to high levels in the glandular trichomes of hops (Humulus lupulus L.). Although all structural enzymes in the XN pathway have been functionally identified, biochemical mechanisms underlying highly efficient production of XN have not been fully resolved. In this study, we characterized two noncatalytic chalcone isomerase (CHI)-like proteins (designated as HlCHIL1 and HlCHIL2) using engineered yeast harboring all genes required for DMX production. HlCHIL2 increased DMX production by 2.3-fold, whereas HlCHIL1 significantly decreased DMX production by 30%. We show that CHIL2 is part of an active DMX biosynthetic metabolon in hop glandular trichomes that encompasses a chalcone synthase (CHS) and a membrane-bound prenyltransferase, and that type IV CHI-fold proteins of representative land plants contain conserved function to bind with CHS and enhance its activity. Binding assays and structural docking uncover a function of HlCHIL1 to bind DMX and naringenin chalcone to stabilize the ring-open configuration of these chalconoids. This study reveals the role of two HlCHILs in DMX biosynthesis in hops, and provides insight into their evolutionary development from the ancestral fatty acid-binding CHI-fold proteins to specialized auxiliary proteins supporting flavonoid biosynthesis in plants.}, } @article {pmid29760091, year = {2018}, author = {Shi, Q and Zhong, Y and Wu, M and Wang, H and Wang, H}, title = {High-capacity rechargeable batteries based on deeply cyclable lithium metal anodes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5676-5680}, pmid = {29760091}, issn = {1091-6490}, abstract = {Discovering new chemistry and materials to enable rechargeable batteries with higher capacity and energy density is of paramount importance. While Li metal is the ultimate choice of a battery anode, its low efficiency is still yet to be overcome. Many strategies have been developed to improve the reversibility and cycle life of Li metal electrodes. However, almost all of the results are limited to shallow cycling conditions (e.g., 1 mAh cm-2) and thus inefficient utilization (<1%). Here we achieve Li metal electrodes that can be deeply cycled at high capacities of 10 and 20 mAh cm-2 with average Coulombic efficiency >98% in a commercial LiPF6/carbonate electrolyte. The high performance is enabled by slow release of LiNO3 into the electrolyte and its subsequent decomposition to form a Li3N and lithium oxynitrides (LiN x Oy)-containing protective layer which renders reversible, dendrite-free, and highly dense Li metal deposition. Using the developed Li metal electrodes, we construct a Li-MoS3 full cell with the anode and cathode materials in a close-to-stoichiometric amount ratio. In terms of both capacity and energy, normalized to either the electrode area or the total mass of the electrode materials, our cell significantly outperforms other laboratory-scale battery cells as well as the state-of-the-art Li ion batteries on the market.}, } @article {pmid29760090, year = {2018}, author = {Zhang, W and Douglas, JF and Starr, FW}, title = {Why we need to look beyond the glass transition temperature to characterize the dynamics of thin supported polymer films.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5641-5646}, pmid = {29760090}, issn = {1091-6490}, abstract = {There is significant variation in the reported magnitude and even the sign of [Formula: see text] shifts in thin polymer films with nominally the same chemistry, film thickness, and supporting substrate. The implicit assumption is that methods used to estimate [Formula: see text] in bulk materials are relevant for inferring dynamic changes in thin films. To test the validity of this assumption, we perform molecular simulations of a coarse-grained polymer melt supported on an attractive substrate. As observed in many experiments, we find that [Formula: see text] based on thermodynamic criteria (temperature dependence of film height or enthalpy) decreases with decreasing film thickness, regardless of the polymer-substrate interaction strength ε. In contrast, we find that [Formula: see text] based on a dynamic criterion (relaxation of the dynamic structure factor) also decreases with decreasing thickness when ε is relatively weak, but [Formula: see text] increases when ε exceeds the polymer-polymer interaction strength. We show that these qualitatively different trends in [Formula: see text] reflect differing sensitivities to the mobility gradient across the film. Apparently, the slowly relaxing polymer segments in the substrate region make the largest contribution to the shift of [Formula: see text] in the dynamic measurement, but this part of the film contributes less to the thermodynamic estimate of [Formula: see text] Our results emphasize the limitations of using [Formula: see text] to infer changes in the dynamics of polymer thin films. However, we show that the thermodynamic and dynamic estimates of [Formula: see text] can be combined to predict local changes in [Formula: see text] near the substrate, providing a simple method to infer information about the mobility gradient.}, } @article {pmid29760089, year = {2018}, author = {Christensen, P and Gillingham, K and Nordhaus, W}, title = {Uncertainty in forecasts of long-run economic growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5409-5414}, pmid = {29760089}, issn = {1091-6490}, abstract = {Forecasts of long-run economic growth are critical inputs into policy decisions being made today on the economy and the environment. Despite its importance, there is a sparse literature on long-run forecasts of economic growth and the uncertainty in such forecasts. This study presents comprehensive probabilistic long-run projections of global and regional per-capita economic growth rates, comparing estimates from an expert survey and a low-frequency econometric approach. Our primary results suggest a median 2010-2100 global growth rate in per-capita gross domestic product of 2.1% per year, with a standard deviation (SD) of 1.1 percentage points, indicating substantially higher uncertainty than is implied in existing forecasts. The larger range of growth rates implies a greater likelihood of extreme climate change outcomes than is currently assumed and has important implications for social insurance programs in the United States.}, } @article {pmid29760088, year = {2018}, author = {McConnell, JR and Wilson, AI and Stohl, A and Arienzo, MM and Chellman, NJ and Eckhardt, S and Thompson, EM and Pollard, AM and Steffensen, JP}, title = {Lead pollution recorded in Greenland ice indicates European emissions tracked plagues, wars, and imperial expansion during antiquity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5726-5731}, pmid = {29760088}, issn = {1091-6490}, mesh = {Armed Conflicts/history ; Disease Outbreaks/history ; *Environmental Pollutants/analysis/history ; Extraction and Processing Industry/history ; Greenland ; History, Ancient ; Humans ; Ice/*analysis ; *Lead/analysis/history ; Roman World/*history ; Silver/history ; }, abstract = {Lead pollution in Arctic ice reflects midlatitude emissions from ancient lead-silver mining and smelting. The few reported measurements have been extrapolated to infer the performance of ancient economies, including comparisons of economic productivity and growth during the Roman Republican and Imperial periods. These studies were based on sparse sampling and inaccurate dating, limiting understanding of trends and specific linkages. Here we show, using a precisely dated record of estimated lead emissions between 1100 BCE and 800 CE derived from subannually resolved measurements in Greenland ice and detailed atmospheric transport modeling, that annual European lead emissions closely varied with historical events, including imperial expansion, wars, and major plagues. Emissions rose coeval with Phoenician expansion, accelerated during expanded Carthaginian and Roman mining primarily in the Iberian Peninsula, and reached a maximum under the Roman Empire. Emissions fluctuated synchronously with wars and political instability particularly during the Roman Republic, and plunged coincident with two major plagues in the second and third centuries, remaining low for >500 years. Bullion in silver coinage declined in parallel, reflecting the importance of lead-silver mining in ancient economies. Our results indicate sustained economic growth during the first two centuries of the Roman Empire, terminated by the second-century Antonine plague.}, } @article {pmid29760087, year = {2018}, author = {Cornforth, DM and Dees, JL and Ibberson, CB and Huse, HK and Mathiesen, IH and Kirketerp-Møller, K and Wolcott, RD and Rumbaugh, KP and Bjarnsholt, T and Whiteley, M}, title = {Pseudomonas aeruginosa transcriptome during human infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5125-E5134}, pmid = {29760087}, issn = {1091-6490}, support = {R01 GM116547/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biofilms ; Cystic Fibrosis ; Disease Models, Animal ; Drug Resistance, Bacterial ; Gene Expression Regulation, Bacterial/genetics/physiology ; Genes, Bacterial ; Humans ; Machine Learning ; Mice ; Pseudomonas Infections/*metabolism/*microbiology ; Pseudomonas aeruginosa/*genetics/isolation & purification/*metabolism ; Quorum Sensing/genetics ; Support Vector Machine ; Surgical Wound Infection/metabolism/microbiology ; Transcriptome/*genetics ; }, abstract = {Laboratory experiments have uncovered many basic aspects of bacterial physiology and behavior. After the past century of mostly in vitro experiments, we now have detailed knowledge of bacterial behavior in standard laboratory conditions, but only a superficial understanding of bacterial functions and behaviors during human infection. It is well-known that the growth and behavior of bacteria are largely dictated by their environment, but how bacterial physiology differs in laboratory models compared with human infections is not known. To address this question, we compared the transcriptome of Pseudomonas aeruginosa during human infection to that of P. aeruginosa in a variety of laboratory conditions. Several pathways, including the bacterium's primary quorum sensing system, had significantly lower expression in human infections than in many laboratory conditions. On the other hand, multiple genes known to confer antibiotic resistance had substantially higher expression in human infection than in laboratory conditions, potentially explaining why antibiotic resistance assays in the clinical laboratory frequently underestimate resistance in patients. Using a standard machine learning technique known as support vector machines, we identified a set of genes whose expression reliably distinguished in vitro conditions from human infections. Finally, we used these support vector machines with binary classification to force P. aeruginosa mouse infection transcriptomes to be classified as human or in vitro. Determining what differentiates our current models from clinical infections is important to better understand bacterial infections and will be necessary to create model systems that more accurately capture the biology of infection.}, } @article {pmid29760086, year = {2018}, author = {Yeung, PS and Yamashita, M and Ing, CE and Pomès, R and Freymann, DM and Prakriya, M}, title = {Mapping the functional anatomy of Orai1 transmembrane domains for CRAC channel gating.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5193-E5202}, pmid = {29760086}, issn = {1091-6490}, support = {R01 GM114210/GM/NIGMS NIH HHS/United States ; R01 NS057499/NS/NINDS NIH HHS/United States ; MOP130461//CIHR/Canada ; T32 GM008152/GM/NIGMS NIH HHS/United States ; T32 GM008382/GM/NIGMS NIH HHS/United States ; S10 RR031680/RR/NCRR NIH HHS/United States ; F31 NS101830/NS/NINDS NIH HHS/United States ; R56 NS057499/NS/NINDS NIH HHS/United States ; }, mesh = {Calcium/*chemistry/*metabolism ; Humans ; Molecular Dynamics Simulation ; ORAI1 Protein/*chemistry/genetics/*metabolism ; Protein Domains ; }, abstract = {Store-operated Orai1 channels are activated through a unique inside-out mechanism involving binding of the endoplasmic reticulum Ca2+ sensor STIM1 to cytoplasmic sites on Orai1. Although atomic-level details of Orai structure, including the pore and putative ligand binding domains, are resolved, how the gating signal is communicated to the pore and opens the gate is unknown. To address this issue, we used scanning mutagenesis to identify 15 residues in transmembrane domains (TMs) 1-4 whose perturbation activates Orai1 channels independently of STIM1. Cysteine accessibility analysis and molecular-dynamics simulations indicated that constitutive activation of the most robust variant, H134S, arises from a pore conformational change that opens a hydrophobic gate to augment pore hydration, similar to gating evoked by STIM1. Mutational analysis of this locus suggests that H134 acts as steric brake to stabilize the closed state of the channel. In addition, atomic packing analysis revealed distinct functional contacts between the TM1 pore helix and the surrounding TM2/3 helices, including one set mediated by a cluster of interdigitating hydrophobic residues and another by alternative ridges of polar and hydrophobic residues. Perturbing these contacts via mutagenesis destabilizes STIM1-mediated Orai1 channel gating, indicating that these bridges between TM1 and the surrounding TM2/3 ring are critical for conveying the gating signal to the pore. These findings help develop a framework for understanding the global conformational changes and allosteric interactions between topologically distinct domains that are essential for activation of Orai1 channels.}, } @article {pmid29760085, year = {2018}, author = {Talukdar, S and Pradhan, AK and Bhoopathi, P and Shen, XN and August, LA and Windle, JJ and Sarkar, D and Furnari, FB and Cavenee, WK and Das, SK and Emdad, L and Fisher, PB}, title = {MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5768-5773}, pmid = {29760085}, issn = {1091-6490}, support = {P30 CA016059/CA/NCI NIH HHS/United States ; P30 NS047463/NS/NINDS NIH HHS/United States ; }, mesh = {Anoikis/*genetics ; Autophagy/*genetics ; Brain Neoplasms/genetics/metabolism ; Drug Resistance, Neoplasm/*genetics ; Glioma/genetics/*metabolism ; Humans ; Neoplastic Stem Cells/*metabolism ; Syntenins/genetics/*metabolism ; Tumor Cells, Cultured ; }, abstract = {Glioma stem cells (GSCs) comprise a small subpopulation of glioblastoma multiforme cells that contribute to therapy resistance, poor prognosis, and tumor recurrence. Protective autophagy promotes resistance of GSCs to anoikis, a form of programmed cell death occurring when anchorage-dependent cells detach from the extracellular matrix. In nonadherent conditions, GSCs display protective autophagy and anoikis-resistance, which correlates with expression of melanoma differentiation associated gene-9/Syntenin (MDA-9) (syndecan binding protein; SDCBP). When MDA-9 is suppressed, GSCs undergo autophagic death supporting the hypothesis that MDA-9 regulates protective autophagy in GSCs under anoikis conditions. MDA-9 maintains protective autophagy through phosphorylation of BCL2 and by suppressing high levels of autophagy through EGFR signaling. MDA-9 promotes these changes by modifying FAK and PKC signaling. Gain-of-function and loss-of-function genetic approaches demonstrate that MDA-9 regulates pEGFR and pBCL2 expression through FAK and pPKC. EGFR signaling inhibits autophagy markers (ATG5, Lamp1, LC3B), helping to maintain protective autophagy, and along with pBCL2 maintain survival of GSCs. In the absence of MDA-9, this protective mechanism is deregulated; EGFR no longer maintains protective autophagy, leading to highly elevated and sustained levels of autophagy and consequently decreased cell survival. In addition, pBCL2 is down-regulated in the absence of MDA-9, leading to cell death in GSCs under conditions of anoikis. Our studies confirm a functional link between MDA-9 expression and protective autophagy in GSCs and show that inhibition of MDA-9 reverses protective autophagy and induces anoikis and cell death in GSCs.}, } @article {pmid29760084, year = {2018}, author = {Hill, DA and Lim, HW and Kim, YH and Ho, WY and Foong, YH and Nelson, VL and Nguyen, HCB and Chegireddy, K and Kim, J and Habertheuer, A and Vallabhajosyula, P and Kambayashi, T and Won, KJ and Lazar, MA}, title = {Distinct macrophage populations direct inflammatory versus physiological changes in adipose tissue.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5096-E5105}, pmid = {29760084}, issn = {1091-6490}, support = {F30 DK112507/DK/NIDDK NIH HHS/United States ; R01 DK049780/DK/NIDDK NIH HHS/United States ; P30 MH097488/MH/NIMH NIH HHS/United States ; T32 HD043021/HD/NICHD NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipose Tissue/*cytology ; Animals ; Exosomes/chemistry ; Female ; Humans ; Inflammation/genetics/*physiopathology ; *Macrophages/chemistry/classification/cytology/metabolism ; Mice ; Mice, Inbred C57BL ; Obesity/metabolism/physiopathology ; Tetraspanin 29/analysis/metabolism ; Transcriptome/genetics ; }, abstract = {Obesity is characterized by an accumulation of macrophages in adipose, some of which form distinct crown-like structures (CLS) around fat cells. While multiple discrete adipose tissue macrophage (ATM) subsets are thought to exist, their respective effects on adipose tissue, and the transcriptional mechanisms that underlie the functional differences between ATM subsets, are not well understood. We report that obese fat tissue of mice and humans contain multiple distinct populations of ATMs with unique tissue distributions, transcriptomes, chromatin landscapes, and functions. Mouse Ly6c ATMs reside outside of CLS and are adipogenic, while CD9 ATMs reside within CLS, are lipid-laden, and are proinflammatory. Adoptive transfer of Ly6c ATMs into lean mice activates gene programs typical of normal adipocyte physiology. By contrast, adoptive transfer of CD9 ATMs drives gene expression that is characteristic of obesity. Importantly, human adipose tissue contains similar ATM populations, including lipid-laden CD9 ATMs that increase with body mass. These results provide a higher resolution of the cellular and functional heterogeneity within ATMs and provide a framework within which to develop new immune-directed therapies for the treatment of obesity and related sequela.}, } @article {pmid29760083, year = {2018}, author = {Hohenegger, C and Stevens, B}, title = {The role of the permanent wilting point in controlling the spatial distribution of precipitation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5692-5697}, pmid = {29760083}, issn = {1091-6490}, abstract = {Convection-permitting simulations on an idealized land planet are performed to understand whether soil moisture acts to support or impede the organization of convection. Initially, shallow circulations driven by differential radiative cooling induce a self-aggregation of the convection into a single band, as has become familiar from simulations over idealized sea surfaces. With time, however, the drying of the nonprecipitating region induces a reversal of the shallow circulation, drawing the flow at low levels from the precipitating to the nonprecipitating region. This causes the precipitating convection to move over the dry soils and reverses the polarity of the circulation. The precipitation replenishes these soils with moisture at the expense of the formerly wet soils which dry, until the process repeats itself. On longer timescales, this acts to homogenize the precipitation field. By analyzing the strength of the shallow circulations, the surface budget with its effects on the boundary layer properties, and the shape of the soil moisture resistance function, we demonstrate that the soil has to dry out significantly, for the here-tested resistance formulations below 15% of its water availability, to be able to alter the precipitation distribution. We expect such a process to broaden the distribution of precipitation over tropical land. This expectation is supported by observations which show that in drier years the monsoon rains move farther inland over Africa.}, } @article {pmid29760082, year = {2018}, author = {Ngo, VL and Abo, H and Maxim, E and Harusato, A and Geem, D and Medina-Contreras, O and Merlin, D and Gewirtz, AT and Nusrat, A and Denning, TL}, title = {A cytokine network involving IL-36γ, IL-23, and IL-22 promotes antimicrobial defense and recovery from intestinal barrier damage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5076-E5085}, pmid = {29760082}, issn = {1091-6490}, support = {R01 DK097256/DK/NIDDK NIH HHS/United States ; R01 DK107739/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Immunity, Innate/*immunology ; Inflammatory Bowel Diseases/*immunology/metabolism ; Interleukins/genetics/*immunology/metabolism ; Intestinal Mucosa/immunology/metabolism ; Mice ; Mice, Transgenic ; Wound Healing/*immunology ; }, abstract = {The gut epithelium acts to separate host immune cells from unrestricted interactions with the microbiota and other environmental stimuli. In response to epithelial damage or dysfunction, immune cells are activated to produce interleukin (IL)-22, which is involved in repair and protection of barrier surfaces. However, the specific pathways leading to IL-22 and associated antimicrobial peptide (AMP) production in response to intestinal tissue damage remain incompletely understood. Here, we define a critical IL-36/IL-23/IL-22 cytokine network that is instrumental for AMP production and host defense. Using a murine model of intestinal damage and repair, we show that IL-36γ is a potent inducer of IL-23 both in vitro and in vivo. IL-36γ-induced IL-23 required Notch2-dependent (CD11b+CD103+) dendritic cells (DCs), but not Batf3-dependent (CD11b-CD103+) DCs or CSF1R-dependent macrophages. The intracellular signaling cascade linking IL-36 receptor (IL-36R) to IL-23 production by DCs involved MyD88 and the NF-κB subunits c-Rel and p50. Consistent with in vitro observations, IL-36R- and IL-36γ-deficient mice exhibited dramatically reduced IL-23, IL-22, and AMP levels, and consequently failed to recover from acute intestinal damage. Interestingly, impaired recovery of mice deficient in IL-36R or IL-36γ could be rescued by treatment with exogenous IL-23. This recovery was accompanied by a restoration of IL-22 and AMP expression in the colon. Collectively, these data define a cytokine network involving IL-36γ, IL-23, and IL-22 that is activated in response to intestinal barrier damage and involved in providing critical host defense.}, } @article {pmid29760081, year = {2018}, author = {Sharp, NP and Sandell, L and James, CG and Otto, SP}, title = {The genome-wide rate and spectrum of spontaneous mutations differ between haploid and diploid yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5046-E5055}, pmid = {29760081}, issn = {1091-6490}, mesh = {DNA Breaks, Double-Stranded ; DNA Repair/genetics ; DNA Replication/genetics ; DNA, Fungal/*genetics ; *Diploidy ; Genes, Fungal/genetics ; *Haploidy ; Mitochondria/genetics ; Mutation/*genetics ; Mutation Rate ; Saccharomyces cerevisiae/*genetics ; }, abstract = {By altering the dynamics of DNA replication and repair, alternative ploidy states may experience different rates and types of new mutations, leading to divergent evolutionary outcomes. We report a direct comparison of the genome-wide spectrum of spontaneous mutations arising in haploids and diploids following a mutation-accumulation experiment in the budding yeast Saccharomyces cerevisiae Characterizing the number, types, locations, and effects of thousands of mutations revealed that haploids were more prone to single-nucleotide mutations (SNMs) and mitochondrial mutations, while larger structural changes were more common in diploids. Mutations were more likely to be detrimental in diploids, even after accounting for the large impact of structural changes, contrary to the prediction that mutations would have weaker effects, due to masking, in diploids. Haploidy is expected to reduce the opportunity for conservative DNA repair involving homologous chromosomes, increasing the insertion-deletion rate, but we found little support for this idea. Instead, haploids were more susceptible to SNMs in late-replicating genomic regions, resulting in a ploidy difference in the spectrum of substitutions. In diploids, we detect mutation rate variation among chromosomes in association with centromere location, a finding that is supported by published polymorphism data. Diploids are not simply doubled haploids; instead, our results predict that the spectrum of spontaneous mutations will substantially shape the dynamics of genome evolution in haploid and diploid populations.}, } @article {pmid29760080, year = {2018}, author = {Morgan, MG}, title = {Uncertainty in long-run forecasts of quantities such as per capita gross domestic product.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5314-5316}, pmid = {29760080}, issn = {1091-6490}, mesh = {*Forecasting ; *Gross Domestic Product ; Health Expenditures ; Uncertainty ; }, } @article {pmid29760079, year = {2018}, author = {Wang, GD and Zhang, BL and Zhou, WW and Li, YX and Jin, JQ and Shao, Y and Yang, HC and Liu, YH and Yan, F and Chen, HM and Jin, L and Gao, F and Zhang, Y and Li, H and Mao, B and Murphy, RW and Wake, DB and Zhang, YP and Che, J}, title = {Selection and environmental adaptation along a path to speciation in the Tibetan frog Nanorana parkeri.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5056-E5065}, pmid = {29760079}, issn = {1091-6490}, mesh = {Animals ; Anura/*genetics/*physiology ; Gene Flow/*genetics ; *Genetic Speciation ; Hybridization, Genetic ; Metagenomics ; Phylogeny ; Selection, Genetic ; Tibet ; }, abstract = {Tibetan frogs, Nanorana parkeri, are differentiated genetically but not morphologically along geographical and elevational gradients in a challenging environment, presenting a unique opportunity to investigate processes leading to speciation. Analyses of whole genomes of 63 frogs reveal population structuring and historical demography, characterized by highly restricted gene flow in a narrow geographic zone lying between matrilines West (W) and East (E). A population found only along a single tributary of the Yalu Zangbu River has the mitogenome only of E, whereas nuclear genes of W comprise 89-95% of the nuclear genome. Selection accounts for 579 broadly scattered, highly divergent regions (HDRs) of the genome, which involve 365 genes. These genes fall into 51 gene ontology (GO) functional classes, 14 of which are likely to be important in driving reproductive isolation. GO enrichment analyses of E reveal many overrepresented functional categories associated with adaptation to high elevations, including blood circulation, response to hypoxia, and UV radiation. Four genes, including DNAJC8 in the brain, TNNC1 and ADORA1 in the heart, and LAMB3 in the lung, differ in levels of expression between low- and high-elevation populations. High-altitude adaptation plays an important role in maintaining and driving continuing divergence and reproductive isolation. Use of total genomes enabled recognition of selection and adaptation in and between populations, as well as documentation of evolution along a stepped cline toward speciation.}, } @article {pmid29760078, year = {2018}, author = {Truttmann, MC and Pincus, D and Ploegh, HL}, title = {Chaperone AMPylation modulates aggregation and toxicity of neurodegenerative disease-associated polypeptides.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5008-E5017}, pmid = {29760078}, issn = {1091-6490}, support = {DP5 OD017941/OD/NIH HHS/United States ; }, mesh = {Adenosine Monophosphate/*metabolism ; Amyloid/metabolism ; Amyloid beta-Peptides/metabolism ; Animals ; Caenorhabditis elegans/metabolism ; Caenorhabditis elegans Proteins/metabolism ; HSP70 Heat-Shock Proteins/metabolism ; Molecular Chaperones/*metabolism ; Neurodegenerative Diseases/*metabolism ; Nucleotidyltransferases/metabolism ; Peptides/*metabolism ; Protein Aggregation, Pathological/*metabolism ; Protein Processing, Post-Translational ; Proteostasis/physiology ; alpha-Synuclein/metabolism ; }, abstract = {Proteostasis is critical to maintain organismal viability, a process counteracted by aging-dependent protein aggregation. Chaperones of the heat shock protein (HSP) family help control proteostasis by reducing the burden of unfolded proteins. They also oversee the formation of protein aggregates. Here, we explore how AMPylation, a posttranslational protein modification that has emerged as a powerful modulator of HSP70 activity, influences the dynamics of protein aggregation. We find that adjustments of cellular AMPylation levels in Caenorhabditis elegans directly affect aggregation properties and associated toxicity of amyloid-β (Aβ), of a polyglutamine (polyQ)-extended polypeptide, and of α-synuclein (α-syn). Expression of a constitutively active C. elegans AMPylase FIC-1(E274G) under its own promoter expedites aggregation of Aβ and α-syn, and drastically reduces their toxicity. A deficiency in AMPylation decreases the cellular tolerance for aggregation-prone polyQ proteins and alters their aggregation behavior. Overexpression of FIC-1(E274G) interferes with cell survival and larval development, underscoring the need for tight control of AMPylase activity in vivo. We thus define a link between HSP70 AMPylation and the dynamics of protein aggregation in neurodegenerative disease models. Our results are consistent with a cytoprotective, rather than a cytotoxic, role for such protein aggregates.}, } @article {pmid29760077, year = {2018}, author = {Edison, JR and Spencer, RK and Butterfoss, GL and Hudson, BC and Hochbaum, AI and Paravastu, AK and Zuckermann, RN and Whitelam, S}, title = {Conformations of peptoids in nanosheets result from the interplay of backbone energetics and intermolecular interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5647-5651}, pmid = {29760077}, issn = {1091-6490}, mesh = {Biomimetic Materials/chemistry ; *Molecular Dynamics Simulation ; Nanostructures/*chemistry/*ultrastructure ; Peptoids/*chemistry ; Polymers ; Protein Structure, Secondary ; }, abstract = {The conformations adopted by the molecular constituents of a supramolecular assembly influence its large-scale order. At the same time, the interactions made in assemblies by molecules can influence their conformations. Here we study this interplay in extended flat nanosheets made from nonnatural sequence-specific peptoid polymers. Nanosheets exist because individual polymers can be linear and untwisted, by virtue of polymer backbone elements adopting alternating rotational states whose twists oppose and cancel. Using molecular dynamics and quantum mechanical simulations, together with experimental data, we explore the design space of flat nanostructures built from peptoids. We show that several sets of peptoid backbone conformations are consistent with their being linear, but the specific combination observed in experiment is determined by a combination of backbone energetics and the interactions made within the nanosheet. Our results provide a molecular model of the peptoid nanosheet consistent with all available experimental data and show that its structure results from a combination of intra- and intermolecular interactions.}, } @article {pmid29760076, year = {2018}, author = {Kaplan, D and Imry, Y}, title = {High-temperature superconductivity using a model of hydrogen bonds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5709-5713}, pmid = {29760076}, issn = {1091-6490}, abstract = {Recently, there has been much interest in high-temperature superconductors and more recently in hydrogen-based superconductors. This work offers a simple model that explains the behavior of the superconducting gap based on naive BCS (Bardeen-Cooper-Schrieffer) theory and reproduces most effects seen in experiments, including the isotope effect and [Formula: see text] enhancement as a function of pressure. We show that this is due to a combination of the factors appearing in the gap equation: the matrix element between the proton states and the level splitting of the proton.}, } @article {pmid29760075, year = {2018}, author = {Chiou, K and Byun, S and Kim, J and Huang, J}, title = {Additive-free carbon nanotube dispersions, pastes, gels, and doughs in cresols.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5703-5708}, pmid = {29760075}, issn = {1091-6490}, abstract = {Cresols are a group of naturally occurring and massively produced methylphenols with broad use in the chemical industry. Here, we report that m-cresol and its liquid mixtures with other isomers are surprisingly good solvents for processing carbon nanotubes. They can disperse carbon nanotubes of various types at unprecedentedly high concentrations of tens of weight percent, without the need for any dispersing agent or additive. Cresols interact with carbon nanotubes by charge transfer through the phenolic hydroxyl proton and can be removed after processing by evaporation or washing, without altering the surface of carbon nanotubes. Cresol solvents render carbon nanotubes polymer-like rheological and viscoelastic properties and processability. As the concentration of nanotubes increases, a continuous transition of four states can be observed, including dilute dispersion, thick paste, free-standing gel, and eventually a kneadable, playdough-like material. As demonstrated with a few proofs of concept, cresols make powders of agglomerated carbon nanotubes immediately usable by a broad array of material-processing techniques to create desirable structures and form factors and make their polymer composites.}, } @article {pmid29760074, year = {2018}, author = {Nakaminami, K and Okamoto, M and Higuchi-Takeuchi, M and Yoshizumi, T and Yamaguchi, Y and Fukao, Y and Shimizu, M and Ohashi, C and Tanaka, M and Matsui, M and Shinozaki, K and Seki, M and Hanada, K}, title = {AtPep3 is a hormone-like peptide that plays a role in the salinity stress tolerance of plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5810-5815}, pmid = {29760074}, issn = {1091-6490}, mesh = {Arabidopsis/*genetics/physiology ; Arabidopsis Proteins/*genetics/physiology ; Genes, Plant/genetics ; Peptide Hormones/*genetics/physiology ; Plants, Genetically Modified/genetics/physiology ; Salt Tolerance/*genetics/physiology ; Seedlings/genetics/physiology ; Stress, Physiological/*genetics ; }, abstract = {Peptides encoded by small coding genes play an important role in plant development, acting in a similar manner as phytohormones. Few hormone-like peptides, however, have been shown to play a role in abiotic stress tolerance. In the current study, 17 Arabidopsis genes coding for small peptides were found to be up-regulated in response to salinity stress. To identify peptides leading salinity stress tolerance, we generated transgenic Arabidopsis plants overexpressing these small coding genes and assessed survivability and root growth under salinity stress conditions. Results indicated that 4 of the 17 overexpressed genes increased salinity stress tolerance. Further studies focused on AtPROPEP3, which was the most highly up-regulated gene under salinity stress. Treatment of plants with synthetic peptides encoded by AtPROPEP3 revealed that a C-terminal peptide fragment (AtPep3) inhibited the salt-induced bleaching of chlorophyll in seedlings. Conversely, knockdown AtPROPEP3 transgenic plants exhibited a hypersensitive phenotype under salinity stress, which was complemented by the AtPep3 peptide. This functional AtPep3 peptide region overlaps with an AtPep3 elicitor peptide that is related to the immune response of plants. Functional analyses with a receptor mutant of AtPep3 revealed that AtPep3 was recognized by the PEPR1 receptor and that it functions to increase salinity stress tolerance in plants. Collectively, these data indicate that AtPep3 plays a significant role in both salinity stress tolerance and immune response in Arabidopsis.}, } @article {pmid29760073, year = {2018}, author = {Kim, KS and Marcogliese, PC and Yang, J and Callaghan, SM and Resende, V and Abdel-Messih, E and Marras, C and Visanji, NP and Huang, J and Schlossmacher, MG and Trinkle-Mulcahy, L and Slack, RS and Lang, AE and , and Park, DS}, title = {Regulation of myeloid cell phagocytosis by LRRK2 via WAVE2 complex stabilization is altered in Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5164-E5173}, pmid = {29760073}, issn = {1091-6490}, support = {148402//CIHR/Canada ; }, mesh = {Animals ; Cell Line ; Cytophagocytosis/*physiology ; Drosophila ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*metabolism ; Mice ; Microglia ; Myeloid Cells/*cytology/physiology ; Parkinson Disease/*physiopathology ; Signal Transduction/physiology ; Wiskott-Aldrich Syndrome Protein Family/*metabolism ; }, abstract = {Leucine-rich repeat kinase 2 (LRRK2) has been implicated in both familial and sporadic Parkinson's disease (PD), yet its pathogenic role remains unclear. A previous screen in Drosophila identified Scar/WAVE (Wiskott-Aldrich syndrome protein-family verproline) proteins as potential genetic interactors of LRRK2 Here, we provide evidence that LRRK2 modulates the phagocytic response of myeloid cells via specific modulation of the actin-cytoskeletal regulator, WAVE2. We demonstrate that macrophages and microglia from LRRK2-G2019S PD patients and mice display a WAVE2-mediated increase in phagocytic response, respectively. Lrrk2 loss results in the opposite effect. LRRK2 binds and phosphorylates Wave2 at Thr470, stabilizing and preventing its proteasomal degradation. Finally, we show that Wave2 also mediates Lrrk2-G2019S-induced dopaminergic neuronal death in both macrophage-midbrain cocultures and in vivo. Taken together, a LRRK2-WAVE2 pathway, which modulates the phagocytic response in mice and human leukocytes, may define an important role for altered immune function in PD.}, } @article {pmid29760072, year = {2018}, author = {D'Errico, F and Goverse, G and Dai, Y and Wu, W and Stakenborg, M and Labeeuw, E and De Simone, V and Verstockt, B and Gomez-Pinilla, PJ and Warner, M and Di Leo, A and Matteoli, G and Gustafsson, JA}, title = {Estrogen receptor β controls proliferation of enteric glia and differentiation of neurons in the myenteric plexus after damage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5798-5803}, pmid = {29760072}, issn = {1091-6490}, mesh = {Animals ; Cell Differentiation/*physiology ; Cell Proliferation/*physiology ; Diet, High-Fat ; Estrogen Receptor beta/*metabolism ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Myenteric Plexus/*cytology/injuries ; Neuroglia/*cytology/metabolism ; Neurons/*cytology/metabolism ; Obesity ; }, abstract = {Injury to the enteric nervous system (ENS) can cause several gastrointestinal (GI) disorders including achalasia, irritable bowel syndrome, and gastroparesis. Recently, a subpopulation of enteric glial cells with neuronal stem/progenitor properties (ENSCs) has been identified in the adult ENS. ENSCs have the ability of reconstituting the enteric neuronal pool after damage of the myenteric plexus. Since the estrogen receptor β (ERβ) is expressed in enteric glial cells and neurons, we investigated whether a selective ERβ agonist, LY3201, can influence neuronal and glial cell differentiation. Myenteric ganglia from the murine muscularis externa were isolated and cultured in either glial cell medium or neuronal medium. In glial cell medium, the number of glial progenitor cells (Sox10+) was increased by fourfold in the presence of LY3201. In the neuronal medium supplemented with an antimitotic agent to block glial cell proliferation, LY3201 elicited a 2.7-fold increase in the number of neurons (neurofilament+ or HuC/D+). In addition, the effect of LY3201 was evaluated in vivo in two murine models of enteric neuronal damage and loss, namely, high-fat diet and topical application of the cationic detergent benzalkonium chloride (BAC) on the intestinal serosa, respectively. In both models, treatment with LY3201 significantly increased the recovery of neurons after damage. Thus, LY3201 was able to stimulate glial-to-neuron cell differentiation in vitro and promoted neurogenesis in the damaged myenteric plexus in vivo. Overall, our study suggests that selective ERβ agonists may represent a therapeutic tool to treat patients suffering from GI disorders, caused by excessive neuronal/glial cell damage.}, } @article {pmid29760071, year = {2018}, author = {Liu, C and Banister, CE and Weige, CC and Altomare, D and Richardson, JH and Contreras, CM and Buckhaults, PJ}, title = {PRDM1 silences stem cell-related genes and inhibits proliferation of human colon tumor organoids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5066-E5075}, pmid = {29760071}, issn = {1091-6490}, support = {P20 GM109091/GM/NIGMS NIH HHS/United States ; P30 GM103336/GM/NIGMS NIH HHS/United States ; U01 CA158428/CA/NCI NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; Cell Proliferation/*physiology ; Clustered Regularly Interspaced Short Palindromic Repeats ; Colon/chemistry/metabolism ; Colonic Neoplasms/genetics/*metabolism/mortality ; Disease-Free Survival ; Humans ; *Organoids/cytology/metabolism ; Positive Regulatory Domain I-Binding Factor 1/genetics/metabolism/*physiology ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {PRDM1 is a tumor suppressor that plays an important role in B and T cell lymphomas. Our previous studies demonstrated that PRDM1β is a p53-response gene in human colorectal cancer cells. However, the function of PRDM1β in colorectal cancer cells and colon tumor organoids is not clear. Here we show that PRDM1β is a p53-response gene in human colon organoids and that low PRDM1 expression predicts poor survival in colon cancer patients. We engineered PRDM1 knockouts and overexpression clones in RKO cells and characterized the PRDM1-dependent transcript landscapes, revealing that both the α and β transcript isoforms repress MYC-response genes and stem cell-related genes. Finally, we show that forced expression of PRDM1 in human colon cancer organoids prevents the formation and growth of colon tumor organoids in vitro. These results suggest that p53 may exert tumor-suppressive effects in part through a PRDM1-dependent silencing of stem cell genes, depleting the size of the normal intestinal stem cell compartment in response to DNA damage.}, } @article {pmid29760070, year = {2018}, author = {Crampton, JS and Meyers, SR and Cooper, RA and Sadler, PM and Foote, M and Harte, D}, title = {Pacing of Paleozoic macroevolutionary rates by Milankovitch grand cycles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5686-5691}, pmid = {29760070}, issn = {1091-6490}, mesh = {Animals ; Biodiversity ; *Biological Evolution ; *Climate ; *Earth (Planet) ; *Extinction, Biological ; Fossils ; }, abstract = {Periodic fluctuations in past biodiversity, speciation, and extinction have been proposed, with extremely long periods ranging from 26 to 62 million years, although forcing mechanisms remain speculative. In contrast, well-understood periodic Milankovitch climate forcing represents a viable driver for macroevolutionary fluctuations, although little evidence for such fluctuation exists except during the Late Cenozoic. The reality, magnitude, and drivers of periodic fluctuations in macroevolutionary rates are of interest given long-standing debate surrounding the relative roles of intrinsic biotic interactions vs. extrinsic environmental factors as drivers of biodiversity change. Here, we show that, over a time span of 60 million years, between 9 and 16% of the variance in biological turnover (i.e., speciation probability plus species extinction probability) in a major Early Paleozoic zooplankton group, the graptoloids, can be explained by long-period astronomical cycles (Milankovitch "grand cycles") associated with Earth's orbital eccentricity (2.6 million years) and obliquity (1.3 million years). These grand cycles modulate climate variability, alternating times of relative stability in the environment with times of maximum volatility. We infer that these cycles influenced graptolite speciation and extinction through climate-driven changes to oceanic circulation and structure. Our results confirm the existence of Milankovitch grand cycles in the Early Paleozoic Era and show that known processes related to the mechanics of the Solar System were shaping marine macroevolutionary rates comparatively early in the history of complex life. We present an application of hidden Markov models to macroevolutionary time series and protocols for the evaluation of statistical significance in spectral analysis.}, } @article {pmid29760069, year = {2018}, author = {Zhou, Z and Liu, J and Rees, TW and Wang, H and Li, X and Chao, H and Stang, PJ}, title = {Heterometallic Ru-Pt metallacycle for two-photon photodynamic therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5664-5669}, pmid = {29760069}, issn = {1091-6490}, support = {R01 CA215157/CA/NCI NIH HHS/United States ; }, mesh = {A549 Cells ; Animals ; Cell Survival/drug effects ; *Coordination Complexes/chemistry/pharmacology ; HeLa Cells ; Humans ; Mice ; Mitochondria/drug effects/metabolism ; Photochemotherapy/*methods ; Photons ; *Photosensitizing Agents/chemistry/pharmacology ; *Platinum/chemistry/pharmacology ; *Ruthenium/chemistry/pharmacology ; Singlet Oxygen/metabolism/pharmacology ; Xenograft Model Antitumor Assays ; }, abstract = {As an effective and noninvasive treatment of various diseases, photodynamic therapy (PTD) relies on the combination of light, a photosensitizer, and oxygen to generate cytotoxic reactive oxygen species that can damage malignant tissue. Much attention has been paid to covalent modifications of the photosensitizers to improve their photophysical properties and to optimize the pathway of the photosensitizers interacting with cells within the target tissue. Herein we report the design and synthesis of a supramolecular heterometallic Ru-Pt metallacycle via coordination-driven self-assembly. While inheriting the excellent photostability and two-photon absorption characteristics of the Ru(II) polypyridyl precursor, the metallacycle also exhibits red-shifted luminescence to the near-infrared region, a larger two-photon absorption cross-section, and higher singlet oxygen generation efficiency, making it an excellent candidate as a photosensitizer for PTD. Cellular studies reveal that the metallacycle selectively accumulates in mitochondria and nuclei upon internalization. As a result, singlet oxygen generated by photoexcitation of the metallacycle can efficiently trigger cell death via the simultaneous damage to mitochondrial function and intranuclear DNA. In vivo studies on tumor-bearing mice show that the metallacycle can efficiently inhibit tumor growth under a low light dose with minimal side effects. The supramolecular approach presented in this work provides a paradigm for the development of PDT agents with high efficacy.}, } @article {pmid29760068, year = {2018}, author = {Holloway, RL and Hurst, SD and Garvin, HM and Schoenemann, PT and Vanti, WB and Berger, LR and Hawks, J}, title = {Endocast morphology of Homo naledi from the Dinaledi Chamber, South Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5738-5743}, pmid = {29760068}, issn = {1091-6490}, support = {R24 NS092988/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Anthropology, Physical ; Biological Evolution ; Brain/*anatomy & histology ; *Fossils ; Hominidae ; Skull/*anatomy & histology ; South Africa ; }, abstract = {Hominin cranial remains from the Dinaledi Chamber, South Africa, represent multiple individuals of the species Homo naledi This species exhibits a small endocranial volume comparable to Australopithecus, combined with several aspects of external cranial anatomy similar to larger-brained species of Homo such as Homo habilis and Homo erectus Here, we describe the endocast anatomy of this recently discovered species. Despite the small size of the H. naledi endocasts, they share several aspects of structure in common with other species of Homo, not found in other hominins or great apes, notably in the organization of the inferior frontal and lateral orbital gyri. The presence of such structural innovations in a small-brained hominin may have relevance to behavioral evolution within the genus Homo.}, } @article {pmid29760067, year = {2018}, author = {Lam, WKJ and Jiang, P and Chan, KCA and Cheng, SH and Zhang, H and Peng, W and Tse, OYO and Tong, YK and Gai, W and Zee, BCY and Ma, BBY and Hui, EP and Chan, ATC and Woo, JKS and Chiu, RWK and Lo, YMD}, title = {Sequencing-based counting and size profiling of plasma Epstein-Barr virus DNA enhance population screening of nasopharyngeal carcinoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5115-E5124}, pmid = {29760067}, issn = {1091-6490}, mesh = {Adult ; *Carcinoma/blood/diagnosis ; Circulating Tumor DNA/*blood ; Cohort Studies ; DNA, Viral/*blood/chemistry/genetics ; Female ; Herpesvirus 4, Human/*genetics ; Humans ; Liquid Biopsy/methods ; Male ; Middle Aged ; Molecular Diagnostic Techniques/methods ; Nasopharyngeal Carcinoma ; *Nasopharyngeal Neoplasms/blood/diagnosis ; Reproducibility of Results ; Viral Load/*methods ; }, abstract = {Circulating tumor-derived DNA testing for cancer screening has recently been demonstrated in a prospective study on identification of nasopharyngeal carcinoma (NPC) among 20,174 asymptomatic individuals. Plasma EBV DNA, a marker for NPC, was detected using real-time PCR. While plasma EBV DNA was persistently detectable in 97.1% of the NPCs identified, ∼5% of the general population had transiently detectable plasma EBV DNA. We hypothesized that EBV DNA in plasma of subjects with or without NPC may have different molecular characteristics. We performed target-capture sequencing of plasma EBV DNA and identified differences in the abundance and size profiles of EBV DNA molecules within plasma of NPC and non-NPC subjects. NPC patients had significantly higher amounts of plasma EBV DNA, which showed longer fragment lengths. Cutoff values were established from an exploratory dataset and tested in a validation sample set. Adopting an algorithm that required a sample to concurrently pass cutoffs for EBV DNA counting and size measurements, NPCs were detected at a positive predictive value (PPV) of 19.6%. This represented superior performance compared with the PPV of 11.0% in the prospective screening study, which required participants with an initially detectable plasma EBV DNA result to be retested within 4 weeks. The observed differences in the molecular nature of EBV DNA molecules in plasma of subjects with or without NPC were successfully translated into a sequencing-based test that had a high PPV for NPC screening and achievable through single time-point testing.}, } @article {pmid29760066, year = {2018}, author = {Chan, MY and Na, J and Agres, PF and Savalia, NK and Park, DC and Wig, GS}, title = {Socioeconomic status moderates age-related differences in the brain's functional network organization and anatomy across the adult lifespan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5144-E5153}, pmid = {29760066}, issn = {1091-6490}, support = {R37 AG006265/AG/NIA NIH HHS/United States ; }, mesh = {Adult ; *Age Factors ; Aged ; Aged, 80 and over ; *Brain/anatomy & histology/diagnostic imaging/physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; *Nerve Net/anatomy & histology/diagnostic imaging/physiology ; Rest/physiology ; *Social Class ; Young Adult ; }, abstract = {An individual's environmental surroundings interact with the development and maturation of their brain. An important aspect of an individual's environment is his or her socioeconomic status (SES), which estimates access to material resources and social prestige. Previous characterizations of the relation between SES and the brain have primarily focused on earlier or later epochs of the lifespan (i.e., childhood, older age). We broaden this work to examine the relationship between SES and the brain across a wide range of human adulthood (20-89 years), including individuals from the less studied middle-age range. SES, defined by education attainment and occupational socioeconomic characteristics, moderates previously reported age-related differences in the brain's functional network organization and whole-brain cortical structure. Across middle age (35-64 years), lower SES is associated with reduced resting-state system segregation (a measure of effective functional network organization). A similar but less robust relationship exists between SES and age with respect to brain anatomy: Lower SES is associated with reduced cortical gray matter thickness in middle age. Conversely, younger and older adulthood do not exhibit consistent SES-related difference in the brain measures. The SES-brain relationships persist after controlling for measures of physical and mental health, cognitive ability, and participant demographics. Critically, an individual's childhood SES cannot account for the relationship between their current SES and functional network organization. These findings provide evidence that SES relates to the brain's functional network organization and anatomy across adult middle age, and that higher SES may be a protective factor against age-related brain decline.}, } @article {pmid29760065, year = {2018}, author = {Harper, CV and Woodcock, DJ and Lam, C and Garcia-Albornoz, M and Adamson, A and Ashall, L and Rowe, W and Downton, P and Schmidt, L and West, S and Spiller, DG and Rand, DA and White, MRH}, title = {Temperature regulates NF-κB dynamics and function through timing of A20 transcription.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5243-E5249}, pmid = {29760065}, issn = {1091-6490}, support = {MR/K015885/1//Medical Research Council/United Kingdom ; BB/K003097/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBF0059382/BB/F0059381/BBF00561X1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F529003/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F005318/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/M008908/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Cell Line, Tumor ; Cells, Cultured ; Cytokines/metabolism ; Gene Expression Regulation/genetics/*physiology ; Gene Knockdown Techniques ; Humans ; Inflammation ; Mice ; NF-kappa B/genetics/*metabolism ; Signal Transduction/genetics/physiology ; Temperature ; Tumor Necrosis Factor alpha-Induced Protein 3/analysis/genetics/*metabolism ; Tumor Necrosis Factor-alpha/*metabolism ; }, abstract = {NF-κB signaling plays a pivotal role in control of the inflammatory response. We investigated how the dynamics and function of NF-κB were affected by temperature within the mammalian physiological range (34 °C to 40 °C). An increase in temperature led to an increase in NF-κB nuclear/cytoplasmic oscillation frequency following Tumor Necrosis Factor alpha (TNFα) stimulation. Mathematical modeling suggested that this temperature sensitivity might be due to an A20-dependent mechanism, and A20 silencing removed the sensitivity to increased temperature. The timing of the early response of a key set of NF-κB target genes showed strong temperature dependence. The cytokine-induced expression of many (but not all) later genes was insensitive to temperature change (suggesting that they might be functionally temperature-compensated). Moreover, a set of temperature- and TNFα-regulated genes were implicated in NF-κB cross-talk with key cell-fate-controlling pathways. In conclusion, NF-κB dynamics and target gene expression are modulated by temperature and can accurately transmit multidimensional information to control inflammation.}, } @article {pmid29760064, year = {2018}, author = {Mizuno, H and Tanaka, K and Yamashiro, S and Narita, A and Watanabe, N}, title = {Helical rotation of the diaphanous-related formin mDia1 generates actin filaments resistant to cofilin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5000-E5007}, pmid = {29760064}, issn = {1091-6490}, mesh = {Actin Cytoskeleton/chemistry/*metabolism ; Actin Depolymerizing Factors/chemistry/*metabolism ; Animals ; Carrier Proteins/chemistry/genetics/*metabolism ; Cell Line ; Fetal Proteins/chemistry/*metabolism ; Mice ; Microfilament Proteins/chemistry/*metabolism ; Mutation ; Nuclear Proteins/chemistry/*metabolism ; Protein Conformation ; Recombinant Proteins/chemistry/genetics/metabolism ; Rotation ; Xenopus laevis ; }, abstract = {The complex interplay between actin regulatory proteins facilitates the formation of diverse cellular actin structures. Formin homology proteins (formins) play an essential role in the formation of actin stress fibers and yeast actin cables, to which the major actin depolymerizing factor cofilin barely associates. In vitro, F-actin decorated with cofilin exhibits a marked increase in the filament twist. On the other hand, a mammalian formin mDia1 rotates along the long-pitch actin helix during processive actin elongation (helical rotation). Helical rotation may impose torsional force on F-actin in the opposite direction of the cofilin-induced twisting. Here, we show that helical rotation of mDia1 converts F-actin resistant to cofilin both in vivo and in vitro. F-actin assembled by mDia1 without rotational freedom became more resistant to the severing and binding activities of cofilin than freely rotatable F-actin. Electron micrographic analysis revealed untwisting of the long-pitch helix of F-actin elongating from mDia1 on tethering of both mDia1 and the pointed end side of the filament. In cells, single molecules of mDia1ΔC63, an activated mutant containing N-terminal regulatory domains, showed tethering to cell structures more frequently than autoinhibited wild-type mDia1 and mDia1 devoid of N-terminal domains. Overexpression of mDia1ΔC63 induced the formation of F-actin, which has prolonged lifetime and accelerates dissociation of cofilin. Helical rotation of formins may thus serve as an F-actin stabilizing mechanism by which a barbed end-bound molecule can enhance the stability of a filament over a long range.}, } @article {pmid29760063, year = {2018}, author = {Martin, JL and Ishmukhametov, R and Spetzler, D and Hornung, T and Frasch, WD}, title = {Elastic coupling power stroke mechanism of the F1-ATPase molecular motor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5750-5755}, pmid = {29760063}, issn = {1091-6490}, support = {R01 GM097510/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/metabolism ; Bacterial Proteins/chemistry/metabolism ; Biochemical Phenomena ; Elasticity ; *Models, Molecular ; Proton-Translocating ATPases/*chemistry/*metabolism ; Thermodynamics ; }, abstract = {The angular velocity profile of the 120° F1-ATPase power stroke was resolved as a function of temperature from 16.3 to 44.6 °C using a ΔμATP = -31.25 kBT at a time resolution of 10 μs. Angular velocities during the first 60° of the power stroke (phase 1) varied inversely with temperature, resulting in negative activation energies with a parabolic dependence. This is direct evidence that phase 1 rotation derives from elastic energy (spring constant, κ = 50 kBT·rad-2). Phase 2 of the power stroke had an enthalpic component indicating that additional energy input occurred to enable the γ-subunit to overcome energy stored by the spring after rotating beyond its 34° equilibrium position. The correlation between the probability distribution of ATP binding to the empty catalytic site and the negative Ea values of the power stroke during phase 1 suggests that this additional energy is derived from the binding of ATP to the empty catalytic site. A second torsion spring (κ = 150 kBT·rad-2; equilibrium position, 90°) was also evident that mitigated the enthalpic cost of phase 2 rotation. The maximum ΔGǂ was 22.6 kBT, and maximum efficiency was 72%. An elastic coupling mechanism is proposed that uses the coiled-coil domain of the γ-subunit rotor as a torsion spring during phase 1, and then as a crankshaft driven by ATP-binding-dependent conformational changes during phase 2 to drive the power stroke.}, } @article {pmid29760062, year = {2018}, author = {}, title = {Correction for Ishikawa et al., Ion-beam irradiation, gene identification, and marker-assisted breeding in the development of low-cadmium rice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4950-E4951}, doi = {10.1073/pnas.1806782115}, pmid = {29760062}, issn = {1091-6490}, } @article {pmid29760061, year = {2018}, author = {Xie, L and Zhang, L and Wang, C and Wang, X and Xu, YM and Yu, H and Wu, P and Li, S and Han, L and Gunatilaka, AAL and Wei, X and Lin, M and Molnár, I and Xu, Y}, title = {Methylglucosylation of aromatic amino and phenolic moieties of drug-like biosynthons by combinatorial biosynthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4980-E4989}, pmid = {29760061}, issn = {1091-6490}, support = {R01 GM114418/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Antineoplastic Agents/metabolism/pharmacology ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Cercopithecus aethiops ; *Drug Discovery ; Fungal Proteins/chemistry/genetics/metabolism ; *Fungi/enzymology/genetics/metabolism ; Glycosylation ; *Glycosyltransferases/chemistry/genetics/metabolism ; Humans ; *Methyltransferases/chemistry/genetics/metabolism ; Polyketide Synthases/chemistry/genetics/metabolism ; Polyketides/metabolism ; Vero Cells ; }, abstract = {Glycosylation is a prominent strategy to optimize the pharmacokinetic and pharmacodynamic properties of drug-like small-molecule scaffolds by modulating their solubility, stability, bioavailability, and bioactivity. Glycosyltransferases applicable for "sugarcoating" various small-molecule acceptors have been isolated and characterized from plants and bacteria, but remained cryptic from filamentous fungi until recently, despite the frequent use of some fungi for whole-cell biocatalytic glycosylations. Here, we use bioinformatic and genomic tools combined with heterologous expression to identify a glycosyltransferase-methyltransferase (GT-MT) gene pair that encodes a methylglucosylation functional module in the ascomycetous fungus Beauveria bassiana The GT is the founding member of a family nonorthologous to characterized fungal enzymes. Using combinatorial biosynthetic and biocatalytic platforms, we reveal that this GT is a promiscuous enzyme that efficiently modifies a broad range of drug-like substrates, including polyketides, anthraquinones, flavonoids, and naphthalenes. It yields both O- and N-glucosides with remarkable regio- and stereospecificity, a spectrum not demonstrated for other characterized fungal enzymes. These glucosides are faithfully processed by the dedicated MT to afford 4-O-methylglucosides. The resulting "unnatural products" show increased solubility, while representative polyketide methylglucosides also display increased stability against glycoside hydrolysis. Upon methylglucosidation, specific polyketides were found to attain cancer cell line-specific antiproliferative or matrix attachment inhibitory activities. These findings will guide genome mining for fungal GTs with novel substrate and product specificities, and empower the efficient combinatorial biosynthesis of a broad range of natural and unnatural glycosides in total biosynthetic or biocatalytic formats.}, } @article {pmid29760060, year = {2018}, author = {Arulpragasam, AR and Cooper, JA and Nuutinen, MR and Treadway, MT}, title = {Corticoinsular circuits encode subjective value expectation and violation for effortful goal-directed behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5233-E5242}, pmid = {29760060}, issn = {1091-6490}, support = {R00 MH102355/MH/NIMH NIH HHS/United States ; R01 MH108605/MH/NIMH NIH HHS/United States ; }, mesh = {Cerebral Cortex/physiology ; Choice Behavior/*physiology ; Female ; *Goals ; Gyrus Cinguli/diagnostic imaging/*physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Prefrontal Cortex/diagnostic imaging/*physiology ; *Reward ; }, abstract = {We are presented with choices each day about how to invest our effort to achieve our goals. Critically, these decisions must frequently be made under conditions of incomplete information, where either the effort required or possible reward to be gained is uncertain. Such choices therefore require the development of potential value estimates to guide effortful goal-directed behavior. To date, however, the neural mechanisms for this expectation process are unknown. Here, we used computational fMRI during an effort-based decision-making task where trial-wise information about effort costs and reward magnitudes was presented separately over time, thereby allowing us to model distinct effort/reward computations as choice-relevant information unfolded. We found that ventromedial prefrontal cortex (vmPFC) encoded expected subjective value. Further, activity in dorsal anterior cingulate (dACC) and anterior insula (aI) reflected both effort discounting as well as a subjective value prediction error signal derived from trial history. While prior studies have identified these regions as being involved in effort-based decision making, these data demonstrate their specific role in the formation and maintenance of subjective value estimates as relevant information becomes available.}, } @article {pmid29760059, year = {2018}, author = {Seifart, F and Strunk, J and Danielsen, S and Hartmann, I and Pakendorf, B and Wichmann, S and Witzlack-Makarevich, A and de Jong, NH and Bickel, B}, title = {Nouns slow down speech across structurally and culturally diverse languages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5720-5725}, pmid = {29760059}, issn = {1091-6490}, mesh = {*Anthropology, Cultural ; Humans ; *Language ; Sound Spectrography ; Speech/*physiology ; Speech Perception ; *Terminology as Topic ; *Vocabulary ; }, abstract = {By force of nature, every bit of spoken language is produced at a particular speed. However, this speed is not constant-speakers regularly speed up and slow down. Variation in speech rate is influenced by a complex combination of factors, including the frequency and predictability of words, their information status, and their position within an utterance. Here, we use speech rate as an index of word-planning effort and focus on the time window during which speakers prepare the production of words from the two major lexical classes, nouns and verbs. We show that, when naturalistic speech is sampled from languages all over the world, there is a robust cross-linguistic tendency for slower speech before nouns compared with verbs, both in terms of slower articulation and more pauses. We attribute this slowdown effect to the increased amount of planning that nouns require compared with verbs. Unlike verbs, nouns can typically only be used when they represent new or unexpected information; otherwise, they have to be replaced by pronouns or be omitted. These conditions on noun use appear to outweigh potential advantages stemming from differences in internal complexity between nouns and verbs. Our findings suggest that, beneath the staggering diversity of grammatical structures and cultural settings, there are robust universals of language processing that are intimately tied to how speakers manage referential information when they communicate with one another.}, } @article {pmid29760058, year = {2018}, author = {Antonelli, A and Zizka, A and Carvalho, FA and Scharn, R and Bacon, CD and Silvestro, D and Condamine, FL}, title = {Amazonia is the primary source of Neotropical biodiversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {6034-6039}, doi = {10.1073/pnas.1713819115}, pmid = {29760058}, issn = {1091-6490}, mesh = {Animals ; Anura ; *Biodiversity ; Biological Evolution ; Birds ; *Ecosystem ; Ferns ; Geology ; Magnoliopsida ; Mammals ; Phylogeny ; Phylogeography ; Plants ; *Rainforest ; South America ; Tropical Climate ; }, abstract = {The American tropics (the Neotropics) are the most species-rich realm on Earth, and for centuries, scientists have attempted to understand the origins and evolution of their biodiversity. It is now clear that different regions and taxonomic groups have responded differently to geological and climatic changes. However, we still lack a basic understanding of how Neotropical biodiversity was assembled over evolutionary timescales. Here we infer the timing and origin of the living biota in all major Neotropical regions by performing a cross-taxonomic biogeographic analysis based on 4,450 species from six major clades across the tree of life (angiosperms, birds, ferns, frogs, mammals, and squamates), and integrate >1.3 million species occurrences with large-scale phylogenies. We report an unprecedented level of biotic interchange among all Neotropical regions, totaling 4,525 dispersal events. About half of these events involved transitions between major environmental types, with a predominant directionality from forested to open biomes. For all taxonomic groups surveyed here, Amazonia is the primary source of Neotropical diversity, providing >2,800 lineages to other regions. Most of these dispersal events were to Mesoamerica (∼1,500 lineages), followed by dispersals into open regions of northern South America and the Cerrado and Chaco biomes. Biotic interchange has taken place for >60 million years and generally increased toward the present. The total amount of time lineages spend in a region appears to be the strongest predictor of migration events. These results demonstrate the complex origin of tropical ecosystems and the key role of biotic interchange for the assembly of regional biotas.}, } @article {pmid29760057, year = {2018}, author = {Cairoli, A and Klages, R and Baule, A}, title = {Weak Galilean invariance as a selection principle for coarse-grained diffusive models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5714-5719}, pmid = {29760057}, issn = {1091-6490}, abstract = {How does the mathematical description of a system change in different reference frames? Galilei first addressed this fundamental question by formulating the famous principle of Galilean invariance. It prescribes that the equations of motion of closed systems remain the same in different inertial frames related by Galilean transformations, thus imposing strong constraints on the dynamical rules. However, real world systems are often described by coarse-grained models integrating complex internal and external interactions indistinguishably as friction and stochastic forces. Since Galilean invariance is then violated, there is seemingly no alternative principle to assess a priori the physical consistency of a given stochastic model in different inertial frames. Here, starting from the Kac-Zwanzig Hamiltonian model generating Brownian motion, we show how Galilean invariance is broken during the coarse-graining procedure when deriving stochastic equations. Our analysis leads to a set of rules characterizing systems in different inertial frames that have to be satisfied by general stochastic models, which we call "weak Galilean invariance." Several well-known stochastic processes are invariant in these terms, except the continuous-time random walk for which we derive the correct invariant description. Our results are particularly relevant for the modeling of biological systems, as they provide a theoretical principle to select physically consistent stochastic models before a validation against experimental data.}, } @article {pmid29760056, year = {2018}, author = {Stears, K and McCauley, DJ and Finlay, JC and Mpemba, J and Warrington, IT and Mutayoba, BM and Power, ME and Dawson, TE and Brashares, JS}, title = {Effects of the hippopotamus on the chemistry and ecology of a changing watershed.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5028-E5037}, pmid = {29760056}, issn = {1091-6490}, mesh = {Animals ; Artiodactyla/*physiology ; *Ecosystem ; Eutrophication/*physiology ; Fishes ; Oxygen/analysis/metabolism ; Rivers/*chemistry ; }, abstract = {Cross-boundary transfers of nutrients can profoundly shape the ecology of recipient systems. The common hippopotamus, Hippopotamus amphibius, is a significant vector of such subsidies from terrestrial to river ecosystems. We compared river pools with high and low densities of H. amphibius to determine how H. amphibius subsidies shape the chemistry and ecology of aquatic communities. Our study watershed, like many in sub-Saharan Africa, has been severely impacted by anthropogenic water abstraction reducing dry-season flow to zero. We conducted observations for multiple years over wet and dry seasons to identify how hydrological variability influences the impacts of H. amphibius During the wet season, when the river was flowing, we detected no differences in water chemistry and nutrient parameters between pools with high and low densities of H. amphibius Likewise, the diversity and abundance of fish and aquatic insect communities were indistinguishable. During the dry season, however, high-density H. amphibius pools differed drastically in almost all measured attributes of water chemistry and exhibited depressed fish and insect diversity and fish abundance compared with low-density H. amphibius pools. Scaled up to the entire watershed, we estimate that H. amphibius in this hydrologically altered watershed reduces dry-season fish abundance and indices of gamma-level diversity by 41% and 16%, respectively, but appears to promote aquatic invertebrate diversity. Widespread human-driven shifts in hydrology appear to redefine the role of H. amphibius, altering their influence on ecosystem diversity and functioning in a fashion that may be more severe than presently appreciated.}, } @article {pmid29760055, year = {2018}, author = {Zhou, T and Li, N and Jin, Y and Zeng, Q and Prabowo, W and Liu, Y and Tian, C and Bao, L and Liu, S and Yuan, Z and Fu, Q and Gao, S and Gao, D and Dunham, R and Shubin, NH and Liu, Z}, title = {Chemokine C-C motif ligand 33 is a key regulator of teleost fish barbel development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5018-E5027}, pmid = {29760055}, issn = {1091-6490}, mesh = {Animals ; Catfishes/genetics/growth & development/metabolism ; Chemokines/genetics/*metabolism/physiology ; Fish Proteins/genetics/*metabolism/physiology ; Gene Expression Profiling ; Genome/genetics ; Male ; Sense Organs/*growth & development/metabolism ; Zebrafish/genetics/growth & development/metabolism ; }, abstract = {Barbels are important sensory organs in teleosts, reptiles, and amphibians. The majority of ∼4,000 catfish species, such as the channel catfish (Ictalurus punctatus), possess abundant whisker-like barbels. However, barbel-less catfish, such as the bottlenose catfish (Ageneiosus marmoratus), do exist. Barbeled catfish and barbel-less catfish are ideal natural models for determination of the genomic basis for barbel development. In this work, we generated and annotated the genome sequences of the bottlenose catfish, conducted comparative and subtractive analyses using genome and transcriptome datasets, and identified differentially expressed genes during barbel regeneration. Here, we report that chemokine C-C motif ligand 33 (ccl33), as a key regulator of barbel development and regeneration. It is present in barbeled fish but absent in barbel-less fish. The ccl33 genes are differentially expressed during barbel regeneration in a timing concordant with the timing of barbel regeneration. Knockout of ccl33 genes in the zebrafish (Danio rerio) resulted in various phenotypes, including complete loss of barbels, reduced barbel sizes, and curly barbels, suggesting that ccl33 is a key regulator of barbel development. Expression analysis indicated that paralogs of the ccl33 gene have both shared and specific expression patterns, most notably expressed highly in various parts of the head, such as the eye, brain, and mouth areas, supporting its role for barbel development.}, } @article {pmid29760054, year = {2018}, author = {Yan, X and Yong, X and Huang, W and Ma, Y}, title = {Placebo treatment facilitates social trust and approach behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5732-5737}, pmid = {29760054}, issn = {1091-6490}, mesh = {Adult ; Choice Behavior/*drug effects ; Female ; Humans ; Interpersonal Relations ; Male ; Oxytocin ; *Placebo Effect ; Placebos/pharmacology ; *Social Behavior ; Trust/*psychology ; Young Adult ; }, abstract = {Placebo effect refers to beneficial changes induced by the use of inert treatment, such as placebo-induced relief of physical pain and attenuation of negative affect. To date, we know little about whether placebo treatment could facilitate social functioning, a crucial aspect for well-being of a social species. In the present study, we develop and validate a paradigm to induce placebo effects on social trust and approach behavior (social placebo effect), and show robust evidence that placebo treatment promotes trust in others and increases preference for a closer interpersonal distance. We further examine placebo effects in real-life social interaction and show that placebo treatment makes single, but not pair-bonded, males keep closer to an attractive first-met female and perceive less social anxiety in the female. Finally, we show evidence that the effects of placebo treatment on social trust and approach behavior can be as strong as the effect of intranasal administration of oxytocin, a neuropeptide known for its function in facilitating social cognition and behavior. The finding of the social placebo effect extends our understanding of placebo effects on improvement of physical, mental, and social well-being and suggests clinical potentials in the treatment of social dysfunction.}, } @article {pmid29760053, year = {2018}, author = {Sun, K and Jiang, P and Wong, AIC and Cheng, YKY and Cheng, SH and Zhang, H and Chan, KCA and Leung, TY and Chiu, RWK and Lo, YMD}, title = {Size-tagged preferred ends in maternal plasma DNA shed light on the production mechanism and show utility in noninvasive prenatal testing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5106-E5114}, pmid = {29760053}, issn = {1091-6490}, mesh = {Case-Control Studies ; Cell-Free Nucleic Acids/*blood/classification ; Female ; Fetus/physiology ; Humans ; Liquid Biopsy ; Molecular Diagnostic Techniques/*methods ; Nucleosomes/chemistry ; Pregnancy ; Prenatal Diagnosis/*methods ; }, abstract = {Cell-free DNA in human plasma is nonrandomly fragmented and reflects genomewide nucleosomal organization. Previous studies had demonstrated tissue-specific preferred end sites in plasma DNA of pregnant women. In this study, we performed integrative analysis of preferred end sites with the size characteristics of plasma DNA fragments. We mined the preferred end sites in short and long plasma DNA molecules separately and found that these "size-tagged" ends showed improved accuracy in fetal DNA fraction estimation and enhanced noninvasive fetal trisomy 21 testing. Further analysis revealed that the fetal and maternal preferred ends were generated from different locations within the nucleosomal structure. Hence, fetal DNA was frequently cut within the nucleosome core while maternal DNA was mostly cut within the linker region. We further demonstrated that the nucleosome accessibility in placental cells was higher than that for white blood cells, which might explain the difference in the cutting positions and the shortness of fetal DNA in maternal plasma. Interestingly, short and long size-tagged ends were also observable in the plasma of nonpregnant healthy subjects and demonstrated size differences similar to those in the pregnant samples. Because the nonpregnant samples did not contain fetal DNA, the data suggested that the interrelationship of preferred DNA ends, chromatin accessibility, and plasma DNA size profile is likely a general one, extending beyond the context of pregnancy. Plasma DNA fragment end patterns have thus shed light on production mechanisms and show utility in future developments in plasma DNA-based noninvasive molecular diagnostics.}, } @article {pmid29760052, year = {2018}, author = {Ryser, MD and Min, BH and Siegmund, KD and Shibata, D}, title = {Spatial mutation patterns as markers of early colorectal tumor cell mobility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5774-5779}, pmid = {29760052}, issn = {1091-6490}, support = {U54 CA217376/CA/NCI NIH HHS/United States ; R21 CA185016/CA/NCI NIH HHS/United States ; K99 CA207872/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; P01 CA196569/CA/NCI NIH HHS/United States ; }, mesh = {Biomarkers, Tumor/*genetics ; Colorectal Neoplasms/*genetics ; Genetic Heterogeneity ; Humans ; Mutation/*genetics ; Neoplasm Invasiveness/*genetics ; }, abstract = {A growing body of evidence suggests that a subset of human cancers grows as single clonal expansions. In such a nearly neutral evolution scenario, it is possible to infer the early ancestral tree of a full-grown tumor. We hypothesized that early tree reconstruction can provide insights into the mobility phenotypes of tumor cells during their first few cell divisions. We explored this hypothesis by means of a computational multiscale model of tumor expansion incorporating the glandular structure of colorectal tumors. After calibrating the model to multiregional and single gland data from 19 human colorectal tumors using approximate Bayesian computation, we examined the role of early tumor cell mobility in shaping the private mutation patterns of the final tumor. The simulations showed that early cell mixing in the first tumor gland can result in side-variegated patterns where the same private mutations could be detected on opposite tumor sides. In contrast, absence of early mixing led to nonvariegated, sectional mutation patterns. These results suggest that the patterns of detectable private mutations in colorectal tumors may be a marker of early cell movement and hence the invasive and metastatic potential of the tumor at the start of the growth. In alignment with our hypothesis, we found evidence of early abnormal cell movement in 9 of 15 invasive colorectal carcinomas ("born to be bad"), but in none of 4 benign adenomas. If validated with a larger dataset, the private mutation patterns may be used for outcome prediction among screen-detected lesions with unknown invasive potential.}, } @article {pmid29760051, year = {2018}, author = {Turk-MacLeod, R and Henson, A and Rodriguez-Garcia, M and Gibson, GM and Aragon Camarasa, G and Caramelli, D and Padgett, MJ and Cronin, L}, title = {Approach to classify, separate, and enrich objects in groups using ensemble sorting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5681-5685}, pmid = {29760051}, issn = {1091-6490}, support = {BB/M011267/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The sorting of objects into groups is a fundamental operation, critical in the preparation and purification of populations of cells, crystals, beads, or droplets, necessary for research and applications in biology, chemistry, and materials science. Most of the efforts exploring such purification have focused on two areas: the degree of separation and the measurement precision required for effective separation. Conventionally, achieving good separation ultimately requires that the objects are considered one by one (which can be both slow and expensive), and the ability to measure the sorted objects by increasing sensitivity as well as reducing sorting errors. Here we present an approach to sorting that addresses both critical limitations with a scheme that allows us to approach the theoretical limit for the accuracy of sorting decisions. Rather than sorting individual objects, we sort the objects in ensembles, via a set of registers which are then in turn sorted themselves into a second symmetric set of registers in a lossless manner. By repeating this process, we can arrive at high sorting purity with a low set of constraints. We demonstrate both the theory behind this idea and identify the critical parameters (ensemble population and sorting time), and show the utility and robustness of our method with simulations and experimental systems spanning several orders of scale, sorting populations of macroscopic beads and microfluidic droplets. Our method is general in nature and simplifies the sorting process, and thus stands to enhance many different areas of science, such as purification, enrichment of rare objects, and separation of dynamic populations.}, } @article {pmid29760050, year = {2018}, author = {Beyerlein, KR and Jönsson, HO and Alonso-Mori, R and Aquila, A and Bajt, S and Barty, A and Bean, R and Koglin, JE and Messerschmidt, M and Ragazzon, D and Sokaras, D and Williams, GJ and Hau-Riege, S and Boutet, S and Chapman, HN and Tîmneanu, N and Caleman, C}, title = {Ultrafast nonthermal heating of water initiated by an X-ray Free-Electron Laser.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5652-5657}, pmid = {29760050}, issn = {1091-6490}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; P41 RR001209/RR/NCRR NIH HHS/United States ; }, mesh = {Crystallography ; *Electrons ; *Hot Temperature ; *Lasers ; Molecular Dynamics Simulation ; Time Factors ; Water/*chemistry ; }, abstract = {The bright ultrafast pulses of X-ray Free-Electron Lasers allow investigation into the structure of matter under extreme conditions. We have used single pulses to ionize and probe water as it undergoes a phase transition from liquid to plasma. We report changes in the structure of liquid water on a femtosecond time scale when irradiated by single 6.86 keV X-ray pulses of more than 106 J/cm2 These observations are supported by simulations based on molecular dynamics and plasma dynamics of a water system that is rapidly ionized and driven out of equilibrium. This exotic ionic and disordered state with the density of a liquid is suggested to be structurally different from a neutral thermally disordered state.}, } @article {pmid29760049, year = {2018}, author = {Bär, L and Feger, M and Fajol, A and Klotz, LO and Zeng, S and Lang, F and Hocher, B and Föller, M}, title = {Insulin suppresses the production of fibroblast growth factor 23 (FGF23).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5804-5809}, pmid = {29760049}, issn = {1091-6490}, mesh = {Animals ; Cell Line, Tumor ; Diabetes Mellitus, Experimental/metabolism ; Female ; Fibroblast Growth Factors/blood/*metabolism ; Gene Expression Regulation/*physiology ; Glucose/administration & dosage/metabolism ; Glucuronidase/metabolism ; Humans ; Insulin/blood/metabolism/*physiology ; Male ; Mice ; Phosphatidylinositol 3-Kinases/metabolism ; Pregnancy ; Proto-Oncogene Proteins c-akt/metabolism ; Rats ; Signal Transduction/physiology ; }, abstract = {Fibroblast growth factor 23 (FGF23) is produced by bone cells and regulates renal phosphate and vitamin D metabolism, as well as causing left ventricular hypertrophy. FGF23 deficiency results in rapid aging, whereas high plasma FGF23 levels are found in several disorders, including kidney or cardiovascular diseases. Regulators of FGF23 production include parathyroid hormone (PTH), calcitriol, dietary phosphate, and inflammation. We report that insulin and insulin-like growth factor 1 (IGF1) are negative regulators of FGF23 production. In UMR106 osteoblast-like cells, insulin and IGF1 down-regulated FGF23 production by inhibiting the transcription factor forkhead box protein O1 (FOXO1) through phosphoinositide 3-kinase (PI3K)/protein kinase B (PKB)/Akt signaling. Insulin deficiency caused a surge in the serum FGF23 concentration in mice, which was reversed by administration of insulin. In women, a highly significant negative correlation between FGF23 plasma concentration and increase in plasma insulin level following an oral glucose load was found. Our results provide strong evidence that insulin/IGF1-dependent PI3K/PKB/Akt/FOXO1 signaling is a powerful suppressor of FGF23 production in vitro as well as in mice and in humans.}, } @article {pmid29759934, year = {2018}, author = {Bell, KC and Carlson, CJ and Phillips, AJ}, title = {Parasite Collections: Overlooked Resources for Integrative Research and Conservation.}, journal = {Trends in parasitology}, volume = {34}, number = {8}, pages = {637-639}, doi = {10.1016/j.pt.2018.04.004}, pmid = {29759934}, issn = {1471-5007}, mesh = {Animals ; Conservation of Natural Resources ; *Parasites ; Parasitology/*standards ; Research/*standards/*trends ; }, abstract = {Parasite natural history collections form vital scientific infrastructure that play a substantial role in increasing awareness of the importance of parasites to ecosystems, conservation assessments, science, and society. These collections support novel investigations that integrate across taxa, time, and space, and should be cultivated to advance organismal-based science. Promoting and supporting parasite collections will ensure their ongoing stability and accessibility.}, } @article {pmid29759926, year = {2018}, author = {Mercorelli, B and Palù, G and Loregian, A}, title = {Drug Repurposing for Viral Infectious Diseases: How Far Are We?.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {865-876}, doi = {10.1016/j.tim.2018.04.004}, pmid = {29759926}, issn = {1878-4380}, abstract = {Despite the recent advances in controlling some viral pathogens, most viral infections still lack specific treatment. Indeed, the need for effective therapeutic strategies to combat 'old', emergent, and re-emergent viruses is not paralleled by the approval of new antivirals. In the past years, drug repurposing combined with innovative approaches for drug validation, and with appropriate animal models, significantly contributed to the identification of new antiviral molecules and targets for therapeutic intervention. In this review, we describe the main strategies of drug repurposing in antiviral discovery, discuss the most promising candidates that could be repurposed to treat viral infections, and analyze the possible caveats of this trendy strategy of drug discovery.}, } @article {pmid29759811, year = {2018}, author = {Li, F and Chen, F and Zhang, S and Gao, X}, title = {Linking spatial grids of the old and new excavations at Zhoukoudian Locality 1, China.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {166-169}, doi = {10.1016/j.jhevol.2018.04.009}, pmid = {29759811}, issn = {1095-8606}, } @article {pmid29759067, year = {2018}, author = {Heintz-Buschart, A and Yusuf, D and Kaysen, A and Etheridge, A and Fritz, JV and May, P and de Beaufort, C and Upadhyaya, BB and Ghosal, A and Galas, DJ and Wilmes, P}, title = {Small RNA profiling of low biomass samples: identification and removal of contaminants.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {52}, pmid = {29759067}, issn = {1741-7007}, support = {U01 HL126496/HL/NHLBI NIH HHS/United States ; }, abstract = {BACKGROUND: Sequencing-based analyses of low-biomass samples are known to be prone to misinterpretation due to the potential presence of contaminating molecules derived from laboratory reagents and environments. DNA contamination has been previously reported, yet contamination with RNA is usually considered to be very unlikely due to its inherent instability. Small RNAs (sRNAs) identified in tissues and bodily fluids, such as blood plasma, have implications for physiology and pathology, and therefore the potential to act as disease biomarkers. Thus, the possibility for RNA contaminants demands careful evaluation.

RESULTS: Herein, we report on the presence of small RNA (sRNA) contaminants in widely used microRNA extraction kits and propose an approach for their depletion. We sequenced sRNAs extracted from human plasma samples and detected important levels of non-human (exogenous) sequences whose source could be traced to the microRNA extraction columns through a careful qPCR-based analysis of several laboratory reagents. Furthermore, we also detected the presence of artefactual sequences related to these contaminants in a range of published datasets, thereby arguing in particular for a re-evaluation of reports suggesting the presence of exogenous RNAs of microbial and dietary origin in blood plasma. To avoid artefacts in future experiments, we also devise several protocols for the removal of contaminant RNAs, define minimal amounts of starting material for artefact-free analyses, and confirm the reduction of contaminant levels for identification of bona fide sequences using 'ultra-clean' extraction kits.

CONCLUSION: This is the first report on the presence of RNA molecules as contaminants in RNA extraction kits. The described protocols should be applied in the future to avoid confounding sRNA studies.}, } @article {pmid29759017, year = {2018}, author = {Rajchert, J and Konopka, K and Boguszewski, P}, title = {Aggression and Helping as Responses to Same-Sex and Opposite-Sex Rejection in Men and Women.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918775253}, doi = {10.1177/1474704918775253}, pmid = {29759017}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Aggression/*psychology ; Female ; *Helping Behavior ; Humans ; *Interpersonal Relations ; Male ; *Rejection (Psychology) ; *Sex Characteristics ; Young Adult ; }, abstract = {Research shows that interpersonal rejection increases aggression and decreases helping toward the rejecter. Based on the assumptions of the evolutionary approach, it was hypothesized that aggression would be higher and helping would be lower after rejection by a same-sex rather than an opposite-sex other. Moreover, it was predicted that the effect for aggression would be stronger in men, and the effect for helping would be stronger in women. Participants (N = 100) were rejected or accepted by a same- or opposite-sex person, and later aggression and helping were measured using the tangram Help-Hurt task. The major finding was that same-sex rejection resulted in more aggression and less helping than opposite-sex rejection, but the rejectee's sex did not moderate the effect. Instead, men were more aggressive and less helping independently of condition. Along with the sexual exchange theory, more negative behavior in same-sex rejection could be interpreted as raised in-group sexual competitive tendencies, whereas less negative behavior in opposite-sex rejection could result from the motivation to exchange resources between men and women.}, } @article {pmid29759010, year = {2018}, author = {Chen, BB}, title = {The Associations Between Social Rank Uncertainty, Machiavellianism, and Dominance: From a Life History Perspective.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918776176}, doi = {10.1177/1474704918776176}, pmid = {29759010}, issn = {1474-7049}, mesh = {Adult ; Female ; *Hierarchy, Social ; Humans ; *Machiavellianism ; Male ; Psychological Theory ; *Social Dominance ; Uncertainty ; Young Adult ; }, abstract = {This study used the life history (LH) theory to investigate how environmental cues are associated with Machiavellianism. A total of 252 undergraduate students completed self-report measures of social rank uncertainty, Machiavellianism, fast LH strategy, and dominance. The results indicated that Machiavellianism was related to a fast LH strategy. Furthermore, a fast LH strategy mediated an association between social rank uncertainty and Machiavellianism. Finally, Machiavellianism was positively associated with dominance. These findings may enhance our understanding of the evolutionary origin of Machiavellianism.}, } @article {pmid29759008, year = {2018}, author = {Furley, P and Schweizer, G and Memmert, D}, title = {Thin Slices of Athletes' Nonverbal Behavior Give Away Game Location: Testing the Territoriality Hypothesis of the Home Game Advantage.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918776456}, doi = {10.1177/1474704918776456}, pmid = {29759008}, issn = {1474-7049}, mesh = {Adult ; Athletes/*psychology ; Female ; Humans ; Male ; Middle Aged ; Nonverbal Communication/*psychology ; Soccer/*psychology ; *Social Perception ; *Territoriality ; Young Adult ; }, abstract = {The present research investigated whether perceivers could detect who is playing at home or away in soccer matches based on thin slices of professional (Experiment 1) and amateur (Experiment 3) athletes' nonverbal behavior prior to the match and whether perceivers rated athletes playing at home relatively higher on behavioral dimensions (Experiments 2 and 3) linked to territoriality. In Experiment 1 (N = 80), participants watched short videos depicting soccer players prior to a UEFA Champions League match and rated whether athletes were more likely to be playing at home or away. In Experiment 2 (two groups N = 102 and N = 101), perceivers rated these videos in terms of assertiveness, dominance, and aggression. In Experiment 3, we replicated the procedure of Experiments 1 and 2 with different stimulus material from amateur soccer (N = 112). Participants could significantly differentiate between home playing and away playing athletes (Experiment 1: d = 0.44 and Experiment 3: d = 1.07). Experiments 2 and 3 showed that perceivers rated professional and amateur soccer players higher on assertiveness (d = 0.34-0.63), dominance (d = 0.20-0.55), and aggression (d = 0.16-0.49) when playing at home compared to playing away. Findings are supportive of evolutionary accounts of nonverbal behavior, ecological approaches to person perception, and the thin slices of behavior hypothesis by demonstrating that humans change their nonverbal behavior depending on game location. We discuss the relevance of the present findings for the home advantage in sports.}, } @article {pmid29758275, year = {2018}, author = {Jabaily, RS and Shepherd, KA and Michener, PS and Bush, CJ and Rivero, R and Gardner, AG and Sessa, EB}, title = {Employing hypothesis testing and data from multiple genomic compartments to resolve recalcitrant backbone nodes in Goodenia s.l. (Goodeniaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {502-512}, doi = {10.1016/j.ympev.2018.05.005}, pmid = {29758275}, issn = {1095-9513}, mesh = {Australia ; Evolution, Molecular ; Genome, Chloroplast ; Genome, Mitochondrial ; Genomics ; Magnoliopsida/*classification/genetics ; Phylogeny ; }, abstract = {Goodeniaceae is a primarily Australian flowering plant family with a complex taxonomy and evolutionary history. Previous phylogenetic analyses have successfully resolved the backbone topology of the largest clade in the family, Goodenia s.l., but have failed to clarify relationships within the species-rich and enigmatic Goodenia clade C, a prerequisite for taxonomic revision of the group. We used genome skimming to retrieve sequences for chloroplast, mitochondrial, and nuclear markers for 24 taxa representing Goodenia s.l., with a particular focus on Goodenia clade C. We performed extensive hypothesis tests to explore incongruence in clade C and evaluate statistical support for clades within this group, using datasets from all three genomic compartments. The mitochondrial dataset is comparable to the chloroplast dataset in providing resolution within Goodenia clade C, though backbone support values within this clade remain low. The hypothesis tests provided an additional, complementary means of evaluating support for clades. We propose that the major subclades of Goodenia clade C (C1-C3 + Verreauxia) are the result of a rapid radiation, and each represents a distinct lineage.}, } @article {pmid29758274, year = {2018}, author = {Tang, Q and Edwards, SV and Rheindt, FE}, title = {Rapid diversification and hybridization have shaped the dynamic history of the genus Elaenia.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {522-533}, doi = {10.1016/j.ympev.2018.05.008}, pmid = {29758274}, issn = {1095-9513}, mesh = {Animals ; Biological Evolution ; Hybridization, Genetic ; Phylogeny ; Songbirds/*classification/genetics ; }, abstract = {Multi-locus data have proven invaluable in phylogenetic reconstruction and species delimitation. However, the mixed genetic signal from different loci can make inference of evolutionary history challenging and may produce incongruences depending on analytical and marker choice. Aside from incomplete lineage sorting (ILS) following diversification events that have had little time for deep differentiation, the most common causes of incongruent phylogenies are genetic introgression confounding a bifurcating evolutionary trajectory. In this study, we used multi-locus analytical approaches on sequence data of nine loci from 80 individuals of over 20 Neotropical Elaenia flycatcher species to examine the systematics, molecular phylogeny and species limits of this complex genus. Our results provide a robust phylogeny and estimates of species limits within Elaenia, but point to important cases of incongruences among phylogenies based on different analytical approaches. Simulations and estimates of divergence times provide reasonable explanations for the incongruent placement of some Elaenia taxa, pointing to multiple cases of both ILS and introgression within the genus. Molecular dating of major evolutionary events revealed intensive diversification during the Pleistocene, suggesting a central role of climate oscillations in the evolution of Elaenia flycatchers.}, } @article {pmid29758179, year = {2018}, author = {Dannenberg, LC and Seaver, EC}, title = {Regeneration of the germline in the annelid Capitella teleta.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {74-87}, doi = {10.1016/j.ydbio.2018.05.004}, pmid = {29758179}, issn = {1095-564X}, mesh = {Animals ; Annelida/*embryology/metabolism ; Body Patterning/physiology ; Cell Lineage/physiology ; Embryo, Nonmammalian/metabolism ; Embryonic Development/physiology ; Embryonic Germ Cells/metabolism/physiology ; Gene Expression Regulation, Developmental/genetics ; Germ Cells/*physiology ; Larva/growth & development ; Mesoderm/embryology ; Polychaeta/genetics ; Regeneration/*physiology ; Stem Cells/physiology ; }, abstract = {The germline is essential for sexual reproduction and survival of the species. In many metazoans, the developmental potential to generate a distinct germline is segregated from somatic cell lineages early in embryogenesis, suggesting that the unique features of the germline must be established from its onset. Previous studies suggest that germ cells cannot regenerate once removed from the embryo, but few animals have been experimentally tested. We investigated the ability of the germline to regenerate in a lophotrochozoan, the segmented worm Capitella teleta, which has a stereotyped cell lineage program by deleting the germline precursor (cell 3D) in early stage embryos using an infrared laser. Larvae and juveniles resulting from germline deletions were examined for presence of multipotent progenitor cells (MPCs), stem cells that form the germ cells and somatic stem cells. In contrast to control deletions of a non-germline macromere, most larvae resulting from deletion of cell 3D lacked MPCs as assayed by expression of germline markers CapI-vasa, CapI-nanos and Ct-piwi1, but showed persistent expression of these markers in the somatic posterior growth zone. However, approximately 13% of experimental larvae had MPCs, indicative of some germline regeneration. In contrast, by two weeks post-metamorphosis, all juveniles resulting from deletion of cell 3D had MPCs, as detected by CapI-vasa expression. Furthermore, when raised to adulthood, most animals developed reproductive structures and were fertile. In another set of deletions, both the D quadrant mesodermal and germline progenitors were removed. These juveniles also regenerated MPCs. Surprisingly, this deletion caused substantial ectopic expression of CapI-vasa and CapI-nanos in other larval tissues. Our results indicate that C. teleta can regenerate the germline following removal of the germline progenitors in the early embryo. The dramatic difference in ability to regenerate the germline between the larval and adult stages suggests that there are two distinct compensation events at two phases of the life cycle: a regulative event in the early stage larva and a stem cell transition event after metamorphosis, when the animals are capable of substantial body regeneration.}, } @article {pmid29758178, year = {2018}, author = {Xia, X and Teotia, P and Ahmad, I}, title = {Lin28a regulates neurogliogenesis in mammalian retina through the Igf signaling.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {113-128}, doi = {10.1016/j.ydbio.2018.05.007}, pmid = {29758178}, issn = {1095-564X}, support = {R01 EY022051/EY/NEI NIH HHS/United States ; P30 GM110768/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/physiology ; Cell Proliferation/physiology ; DNA-Binding Proteins/metabolism ; Female ; Gene Expression Regulation, Developmental/genetics ; Insulin-Like Growth Factor I/metabolism/physiology ; Male ; Mice ; Mice, Transgenic ; MicroRNAs/genetics ; Neurogenesis/genetics/*physiology ; Neuroglia/metabolism/*physiology ; Neurons/metabolism/physiology ; RNA-Binding Proteins/genetics/*metabolism/physiology ; Rats ; Rats, Sprague-Dawley ; Retina/metabolism ; Signal Transduction ; Stem Cells/metabolism ; }, abstract = {In the developing central nervous system (CNS) the majority of neurons are born before the generation of glia. Emerging evidence implicates heterochronic gene, Lin28 in the temporal switch between two distinct lineages. However, the respective contributions of Lin28a and Lin28b in neurogliogenesis remain poorly understood. Here, we have examined the relative involvement of Lin28a and Lin28b in mammalian retina, a simple and accessible CNS model where neurogliogenic decision largely occurs postnatally. Examination of Lin28a/b involvement during late histogenesis by the perturbation of function approaches revealed that while Lin28b did not influence differentiation in general Lin28a facilitated and antagonized the generation of neurons and glia, respectively. Silencing of Lin28a expression in vitro and its conditional deletion in vivo during early histogenesis led to premature generation of glia. The instructive role of Lin28a on neuronal differentiation was revealed by its influence to suppress glial-specific genes and directly differentiate glia along the neuronal lineage. This function of Lin28a is likely mediated through the Igf signaling, as inhibition of the pathway abrogated Lin28a-mediated neurogliogenesis. Thus, our observations suggest that Lin28a is an important intrinsic factor that acts in concert with cell-extrinsic factors like Igfs, coordinating the developmental bias of the progenitors and niche, respectively, for the successive generation of neurons and glia.}, } @article {pmid29757129, year = {2018}, author = {Kämpfer, P and Glaeser, SP and Gräber, M and Rabenstein, A and Kuever, J}, title = {Qingshengfania soli Zhang et al. 2015 is a later heterotypic synonym of Pseudochelatococcus lubricantis Kämpfer et al. 2015.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2240-2241}, doi = {10.1099/ijsem.0.002817}, pmid = {29757129}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Beijerinckiaceae/*classification/genetics ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {Qingshengfania soli DSM 103870T was compared with Pseudochelatococcus lubricantis MPA 1113T to clarify the taxonomic relationship of both species because of their high phylogenetic relationship. 16S rRNA gene sequence comparisons demonstrated that these species share 100 % sequence similarity. Investigation of fatty acid patterns, substrate utilization, and matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) profiles displayed no striking differences between the type strains of both species. DNA-DNA hybridization between both strains showed a 95 % (reciprocal 82 %) similarity, which clearly demonstrated that both strains are members of the same species. Due to priority of publication and validation of the name, Qingshengfania soli is reclassified as Pseudochelatococcus lubricantis, based on the estimated phylogenetic position derived from 16S rRNA gene sequence data, fatty acid, biochemical data, MALDI-TOF, and DNA-DNA hybridization results.}, } @article {pmid29757127, year = {2018}, author = {Mori, K and Yamaguchi, K and Hanada, S}, title = {Sulfurovum denitrificans sp. nov., an obligately chemolithoautotrophic sulfur-oxidizing epsilonproteobacterium isolated from a hydrothermal field.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2183-2187}, doi = {10.1099/ijsem.0.002803}, pmid = {29757127}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Epsilonproteobacteria/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Oxidation-Reduction ; Pacific Ocean ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Sulfur/*metabolism ; Sulfur-Reducing Bacteria/classification/genetics/isolation & purification ; Thiosulfates/metabolism ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel marine sulfur-oxidizing bacterium, designated strain eps51T, was isolated from a surface rock sample collected from the hydrothermal field of Suiyo Seamount on the Izu-Bonin Arc in the Western Pacific Ocean. This bacterium was Gram-staining-negative, non-motile and rod-shaped. Strain eps51T grew chemolithoautotrophically, by sulfur-oxidizing respiration with elemental sulfur and thiosulfate as electron donors and used only carbon dioxide as a carbon source. Oxygen and nitrate were used as its electron acceptors. The isolate grew optimally at 30 °C, at pH 7.0 and with 3 % NaCl. The predominant fatty acids were C16 : 1ω7c, C18 : 1ω7c and C16 : 0. The respiratory quinone was menaquinone-6 and the genomic DNA G+C content was 40.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequence revealed that eps51T represented a member of the genus Sulfurovum and the closest relative was Sulfurovum aggregans (96.7 %). Based on its phylogenetic position along with its physiological and chemotaxonomic characteristics, the name Sulfurovum denitrificans sp. nov. is proposed, with the type strain eps51T (=NBRC 102602T=DSM 19611T).}, } @article {pmid29755717, year = {2018}, author = {Van Belleghem, SM and Papa, R and Ortiz-Zuazaga, H and Hendrickx, F and Jiggins, CD and McMillan, WO and Counterman, BA}, title = {patternize: An R package for quantifying colour pattern variation.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {2}, pages = {390-398}, pmid = {29755717}, issn = {2041-210X}, support = {P20 GM103475/GM/NIGMS NIH HHS/United States ; }, abstract = {The use of image data to quantify, study and compare variation in the colors and patterns of organisms requires the alignment of images to establish homology, followed by color-based segmentation of images. Here we describe an R package for image alignment and segmentation that has applications to quantify color patterns in a wide range of organisms. patternize is an R package that quantifies variation in color patterns obtained from image data. patternize first defines homology between pattern positions across specimens either through manually placed homologous landmarks or automated image registration. Pattern identification is performed by categorizing the distribution of colors using an RGB threshold, k-means clustering or watershed transformation.We demonstrate that patternize can be used for quantification of the color patterns in a variety of organisms by analyzing image data for butterflies, guppies, spiders and salamanders. Image data can be compared between sets of specimens, visualized as heatmaps and analyzed using principal component analysis (PCA). patternize has potential applications for fine scale quantification of color pattern phenotypes in population comparisons, genetic association studies and investigating the basis of color pattern variation across a wide range of organisms.}, } @article {pmid29755252, year = {2018}, author = {Napoli, JG and Williamson, TE and Shelley, SL and Brusatte, SL}, title = {A Digital Endocranial Cast of the Early Paleocene (Puercan) 'Archaic' Mammal Onychodectes tisonensis (Eutheria: Taeniodonta).}, journal = {Journal of mammalian evolution}, volume = {25}, number = {2}, pages = {179-195}, pmid = {29755252}, issn = {1064-7554}, abstract = {Eutherian mammals-placentals and their closest extinct relatives-underwent a major radiation following the end-Cretaceous extinction, during which they evolved disparate anatomy and established new terrestrial ecosystems. Much about the timing, pace, and causes of this radiation remain unclear, in large part because we still know very little about the anatomy, phylogenetic relationships, and biology of the so-called 'archaic' eutherians that prospered during the ~10 million years after the extinction. We describe the first digital endocranial cast of a taeniodont, a bizarre group of eutherians that flourished in the early Paleogene, reconstructed from a computed tomography (CT) scan of a late Puercan (65.4 million year old) specimen of Onychodectes tisonensis that recovered most of the forebrain and midbrain and portions of the inner ear. Notable features of the endocast include long, broad olfactory bulbs, dorsally-positioned rhinal fissures, and a lissencephalic cerebrum. Comparison with other taxa shows that Onychodectes possessed some of the largest olfactory bulbs (relative to cerebral size) of any known mammal. Statistical analysis of modern mammals shows that relative olfactory bulb dimensions are not strongly correlated with body size or fossorial digging for shelter, but relative bulb width is significantly greater in taxa that habitually dig to forage for food. The anatomical description and statistical results allow us to present an ecological model for Onychodectes and similar taeniodonts, in which they are animals of simple behavior that rely on a strong sense of smell to locate buried food before extracting and processing it with their specialized skeletal anatomy.}, } @article {pmid29755159, year = {2018}, author = {Parker, D}, title = {Kuhnian revolutions in neuroscience: the role of tool development.}, journal = {Biology & philosophy}, volume = {33}, number = {3}, pages = {17}, pmid = {29755159}, issn = {0169-3867}, abstract = {The terms "paradigm" and "paradigm shift" originated in "The Structure of Scientific Revolutions" by Thomas Kuhn. A paradigm can be defined as the generally accepted concepts and practices of a field, and a paradigm shift its replacement in a scientific revolution. A paradigm shift results from a crisis caused by anomalies in a paradigm that reduce its usefulness to a field. Claims of paradigm shifts and revolutions are made frequently in the neurosciences. In this article I will consider neuroscience paradigms, and the claim that new tools and techniques rather than crises have driven paradigm shifts. I will argue that tool development has played a minor role in neuroscience revolutions.}, } @article {pmid29755152, year = {2018}, author = {Segura-García, I and Rojo-Arreola, L and Rocha-Olivares, A and Heckel, G and Gallo-Reynoso, JP and Hoelzel, R}, title = {Eco-Evolutionary Processes Generating Diversity Among Bottlenose Dolphin, Tursiops truncatus, Populations off Baja California, Mexico.}, journal = {Evolutionary biology}, volume = {45}, number = {2}, pages = {223-236}, pmid = {29755152}, issn = {0071-3260}, abstract = {For highly mobile species that nevertheless show fine-scale patterns of population genetic structure, the relevant evolutionary mechanisms determining structure remain poorly understood. The bottlenose dolphin (Tursiops truncatus) is one such species, exhibiting complex patterns of genetic structure associated with local habitat dependence in various geographic regions. Here we studied bottlenose dolphin populations in the Gulf of California and Pacific Ocean off Baja California where habitat is highly structured to test associations between ecology, habitat dependence and genetic differentiation. We investigated population structure at a fine geographic scale using both stable isotope analysis (to assess feeding ecology) and molecular genetic markers (to assess population structure). Our results show that there are at least two factors affecting population structure for both genetics and feeding ecology (as indicated by stable isotope profiles). On the one hand there is a signal for the differentiation of individuals by ecotype, one foraging more offshore than the other. At the same time, there is differentiation between the Gulf of California and the west coast of Baja California, meaning that for example, nearshore ecotypes were both genetically and isotopically differentiated either side of the peninsula. We discuss these data in the context of similar studies showing fine-scale population structure for delphinid species in coastal waters, and consider possible evolutionary mechanisms.}, } @article {pmid29755151, year = {2018}, author = {Randau, M and Goswami, A}, title = {Shape Covariation (or the Lack Thereof) Between Vertebrae and Other Skeletal Traits in Felids: The Whole is Not Always Greater than the Sum of Parts.}, journal = {Evolutionary biology}, volume = {45}, number = {2}, pages = {196-210}, pmid = {29755151}, issn = {0071-3260}, abstract = {Within carnivorans, cats show comparatively little disparity in overall morphology, with species differing mainly in body size. However, detailed shape analyses of individual osteological structures, such as limbs or skulls, have shown that felids display significant morphological differences that correlate with their observed ecological and behavioural ranges. Recently, these shape analyses have been extended to the felid axial skeleton. Results demonstrate a functionally-partitioned vertebral column, with regions varying greatly in level of correlation between shape and ecology. Moreover, a clear distinction is evident between a phylogenetically-constrained neck region and a selection-responsive posterior spine. Here, we test whether this regionalisation of function reflected in vertebral column shape is also translated into varying levels of phenotypic integration between this structure and most other skeletal elements. We accomplish this comparison by performing pairwise tests of integration between vertebral and other osteological units, quantified with 3D geometric morphometric data and analysed both with and without phylogenetic correction. To our knowledge, this is the first study to test for integration across a comprehensive sample of whole-skeleton elements. Our results show that, prior to corrections, strong covariation is present between vertebrae across the vertebral column and all other elements, with the exception of the femur. However, most of these significant correlations disappear after correcting for phylogeny, which is a significant influence on cranial and limb morphology of felids and other carnivorans. Our results thus suggest that the vertebral column of cats displays relative independence from other skeletal elements and may represent several distinct evolutionary morphological modules.}, } @article {pmid29754971, year = {2018}, author = {An, SQ and Berg, G}, title = {Stenotrophomonas maltophilia.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {637-638}, doi = {10.1016/j.tim.2018.04.006}, pmid = {29754971}, issn = {1878-4380}, abstract = {This infographic describes the key regulated traits of Stenotrophomonas maltophilia, important for beneficial plant interactions, and also its increasing incidence as a nosocomial and community-acquired infection. Stenotrophomonas maltophilia is a cosmopolitan and ubiquitous bacterium found in a range of environmental habitats, including extreme ones, although in nature it is mainly associated with plants. S. maltophilia fulfils important ecosystem functions in the sulfur and nitrogen cycles, in degradation of complex compounds and pollutants, and in promoti on of plant growth and health. Stenotrophomonas can also colonize extreme man-made niches in hospitals, space shuttles, and clean rooms. S. maltophilia has emerged as a global opportunistic human pathogen, which does not usually infect healthy hosts but is associated with high morbidity and mortality in severely immunocompromised and debilitated individuals. S. maltophilia can also be recovered from polymicrobial infections, most notably from the respiratory tract of cystic fibrosis patients. Close relatives of S. maltophilia, for example, S. rhizophila, provide a harmless alternative for biotechnological applications without human health risks.}, } @article {pmid29754810, year = {2018}, author = {Ripple, WJ and Meijaard, E and Newsome, T}, title = {Saving the World with Satire: A Response to Chapron et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {483-484}, doi = {10.1016/j.tree.2018.04.011}, pmid = {29754810}, issn = {1872-8383}, } @article {pmid29754744, year = {2018}, author = {García-Martínez, D and Campo Martín, M and González Martín, A and Cambra-Moo, Ó and Barash, A and Bastir, M}, title = {Reevaluation of 'endocostal ossifications' on the Kebara 2 Neanderthal ribs.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {33-37}, doi = {10.1016/j.jhevol.2018.04.011}, pmid = {29754744}, issn = {1095-8606}, } @article {pmid29754743, year = {2018}, author = {Cunningham, DL and Graves, RR and Wescott, DJ and McCarthy, RC}, title = {The effect of ontogeny on estimates of KNM-WT 15000's adult body size.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {119-127}, doi = {10.1016/j.jhevol.2018.04.002}, pmid = {29754743}, issn = {1095-8606}, abstract = {The Homo erectus specimen KNM-WT 15000 has played a critical role in our understanding of body size evolution. New interpretations suggest that KNM-WT 15000 had a younger age-at-death and a more rapid ontogenetic trajectory than previously suggested. Recent fossil discoveries and new interpretations suggest a wide range of body size and shape variation in H. erectus. Based on these new insights, we argue that KNM-WT 15000's adult stature and body mass could have been much smaller than has been traditionally presented in the literature. Using chimpanzee and modern human growth trajectories, we bracketed the range of possibilities for KNM-WT 15000's adult body size between 160.0 and 177.7 cm (5'3″-5'10″) for stature and 60.0 and 82.7 kg (132-182 lbs.) for body mass. These estimates put KNM-WT 15000 near the mean rather than among the largest known H. erectus specimens.}, } @article {pmid29754742, year = {2018}, author = {Lazaridis, G and Tsoukala, E and Rae, TC and Gómez-Olivencia, A and Nagel, D and Bartsiokas, A}, title = {Mesopithecus pentelicus from the Turolian locality of Kryopigi (Kassandra, Chalkidiki, Greece).}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {128-146}, doi = {10.1016/j.jhevol.2018.04.003}, pmid = {29754742}, issn = {1095-8606}, abstract = {New material of the Mio-Pliocene colobine Mesopithecus from the Turolian locality of Kryopigi (Greece) is described here. It includes a complete skull with the atlas attached and other dental and postcranial elements representing at least five individuals (four males and one female). The material is compared with Mesopithecus delsoni, Mesopithecus pentelicus, Mesopithecus monspessulanus and intermediate forms from more than a dozen Turolian localities of the Greco-Iranian province. These comparisons support the attribution of the Kryopigi material to M. pentelicus. The chronostratigraphic distribution of Mesopithecus species and intermediate forms suggests that the Kryopigi fauna could be dated as younger than the Perivolaki locality with M. delsoni/pentelicus (7.1-7.3 Ma, MN12) and older than the Dytiko localities with M. aff. pentelicus, M. cf. pentelicus and M. cf. monspessulanus (?middle MN13). The dimensions of the atlas are within the distribution of extant colobines. The skull shows bite-marks, probably caused by the hyaena Adcrocuta eximia.}, } @article {pmid29754586, year = {2018}, author = {Ishtiaq, F and Barve, S}, title = {Do avian blood parasites influence hypoxia physiology in a high elevation environment?.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {15}, pmid = {29754586}, issn = {1472-6785}, support = {//Wellcome Trust/United Kingdom ; IA/S/12/2/500629//Wellcome Trust-DBT India Alliance/India ; IA/I(S)/12/2/500629//DBT India Alliance/International ; }, abstract = {BACKGROUND: Montane birds which engage in elevational movements have evolved to cope with fluctuations in environmental hypoxia, through changes in physiological parameters associated with blood oxygen-carrying capacity such as haemoglobin concentration (Hb) and haematocrit (Hct). In particular, elevational migrants which winter at low elevations, encounter varying intensities of avian haemosporidian parasites as they traverse heterogeneous environments. Whilst high intensity parasite infections lead to anaemia, one can expect that the ability to cope with haemosporidian infections should be a key trait for elevational migrants that must be balanced against reducing the oxygen-carrying capacity of blood in response to high elevation. In this study, we explored the links between environmental hypoxia, migration, and disease ecology by examining natural variation in infections status and intensity of avian haemoporidians across a suite of Himalayan birds with different migratory strategies while controlling for host phylogeny.

RESULTS: We found predictably large variation in haemoglobin levels across the elevational gradient and this pattern was strongly influenced by season and whether birds are elevational migrants. The overall malaria infection intensity declined with elevation whereas Hb and Hct decreased with increase in parasite intensity, suggesting an important role of malaria parasites on hypoxia stressed birds in high elevation environments.

CONCLUSIONS: Our results provide a key insight into how physiological measures and sub-clinical infections might affect dynamics of high-elevation bird populations. We suggest a potential impact of avian elevational migration on disease dynamics and exposure to high intensity infections with disease spread in the face of climate change, which will exacerbate hypoxic stress and negative effects of chronic avian malaria infection on survival and reproductive success in wild birds. Future work on chronic parasite infections must consider parasite intensity, rather than relying on infection status alone.}, } @article {pmid29754180, year = {2018}, author = {Zhou, J and Duan, J and Gao, M and Wang, Y and Wang, X and Zhao, K}, title = {Diversity, Roles, and Biotechnological Applications of Symbiotic Microorganisms in the Gut of Termite.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1502-4}, pmid = {29754180}, issn = {1432-0991}, support = {2014RFXXJ081//Technological innovation talent of special funds for outstanding subject leaders in Harbin/ ; 20170160908//Special Project of Graduate Entrepreneurship of Heilongjiang University/ ; }, abstract = {Termites are global pests and can cause serious damage to buildings, crops, and plantation forests. The symbiotic intestinal flora plays an important role in the digestion of cellulose and nitrogen in the life of termites. Termites and their symbiotic microbes in the gut form a synergistic system. These organism work together to digest lignocellulose to make the termites grow on nitrogen deficient food. In this paper, the diversity of symbiotic microorganisms in the gut of termites, including protozoan, spirochetes, actinomycetes, fungus and bacteria, and their role in the digestion of lignocellulose and also the biotechnological applications of these symbiotic microorganisms are discussed. The high efficiency lignocellulose degradation systems of symbiotic microbes in termite gut not only provided a new way of biological energy development, but also has immense prospect in the application of cellulase enzymes. In addition, the study on the symbiotic microorganisms in the gut of termites will also provide a new method for the biological control of termites by the endophytic bacteria in the gut of termites.}, } @article {pmid29753711, year = {2018}, author = {Moner, AM and Furtado, A and Henry, RJ}, title = {Chloroplast phylogeography of AA genome rice species.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {475-487}, doi = {10.1016/j.ympev.2018.05.002}, pmid = {29753711}, issn = {1095-9513}, abstract = {Whole chloroplast genome sequence analysis of 58 wild and domesticated rice samples was used to investigate their phylogeny providing more detail on the biogeography of the major groups of wild A genome rices globally. An optimized chloroplast assembly method was developed and applied to extracting high quality whole chloroplast genome sequences from shot gun whole DNA sequencing data. Forty complete high quality chloroplast genome sequences were assembled (including; temperate japonica, tropical japonica and aus). South American, African wild rice relationship were conformed, while the Australian chloroplast type was found to extend north to the Philippines. The remainder could be divided into an African (O. barthii and the domesticated O. glaberrima) clade and the Asian taxa. The Asian taxa was placed in two distinct clades including the domesticated O. sativa ssp. indica and O. sativa ssp. japonica respectively. These two groups of wild rices had substantially overlapping distributions with the O. sativa japonica group extending further west into India. The aromatic rices had japonica chloroplasts as expected. A polyphyletic maternal genome origin of the cultivated aus group of rices was suggested by the identification of aus accessions in both the indica and japonica clades. The current distribution of the chloroplast types appears to differ significantly to that of the nuclear genome diversity suggesting a complex evolutionary history of the rice progenitors leading to the domestication of rice.}, } @article {pmid29753710, year = {2018}, author = {Mácová, A and Hoblíková, A and Hypša, V and Stanko, M and Martinů, J and Kvičerová, J}, title = {Mysteries of host switching: Diversification and host specificity in rodent-coccidia associations.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {179-189}, doi = {10.1016/j.ympev.2018.05.009}, pmid = {29753710}, issn = {1095-9513}, abstract = {Recent studies show that host switching is much more frequent than originally believed and constitutes an important driver in evolution of host-parasite associations. However, its frequency and ecological mechanisms at the population level have been rarely investigated. We address this issue by analyzing phylogeny and population genetics of an extensive sample, from a broad geographic area, for commonly occurring parasites of the genus Eimeria within the abundant rodent genera Apodemus, Microtus and Myodes, using two molecular markers. At the most basal level, we demonstrate polyphyletic arrangement, i.e. multiple origin, of the rodent-specific clusters within the Eimeria phylogeny, and strong genetic/phylogenetic structure within these lineages determined at least partially by specificities to different host groups. However, a novel and the most important observation is a repeated occurrence of host switches among closely related genetic lineages which may become rapidly fixed. Within the studied model, this phenomenon applies particularly to the switches between the eimerians from Apodemus flavicollis/Apodemus sylvaticus and Apodemus agrarius groups. We show that genetic differentiation and isolation between A. flavicollis/A. sylvaticus and A. agrarius faunas is a secondary recent event and does not reflect host-parasite coevolutionary history. Rather, it provides an example of rapid ecology-based differentiation in the parasite population.}, } @article {pmid29753626, year = {2018}, author = {Woronowicz, KC and Gline, SE and Herfat, ST and Fields, AJ and Schneider, RA}, title = {FGF and TGFβ signaling link form and function during jaw development and evolution.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29753626}, issn = {1095-564X}, support = {R01 DE025668/DE/NIDCR NIH HHS/United States ; S10 OD021664/OD/NIH HHS/United States ; T32 HD007470/HD/NICHD NIH HHS/United States ; }, abstract = {How does form arise during development and change during evolution? How does form relate to function, and what enables embryonic structures to presage their later use in adults? To address these questions, we leverage the distinct functional morphology of the jaw in duck, chick, and quail. In connection with their specialized mode of feeding, duck develop a secondary cartilage at the tendon insertion of their jaw adductor muscle on the mandible. An equivalent cartilage is absent in chick and quail. We hypothesize that species-specific jaw architecture and mechanical forces promote secondary cartilage in duck through the differential regulation of FGF and TGFβ signaling. First, we perform transplants between chick and duck embryos and demonstrate that the ability of neural crest mesenchyme (NCM) to direct the species-specific insertion of muscle and the formation of secondary cartilage depends upon the amount and spatial distribution of NCM-derived connective tissues. Second, we quantify motility and build finite element models of the jaw complex in duck and quail, which reveals a link between species-specific jaw architecture and the predicted mechanical force environment. Third, we investigate the extent to which mechanical load mediates FGF and TGFβ signaling in the duck jaw adductor insertion, and discover that both pathways are mechano-responsive and required for secondary cartilage formation. Additionally, we find that FGF and TGFβ signaling can also induce secondary cartilage in the absence of mechanical force or in the adductor insertion of quail embryos. Thus, our results provide novel insights on molecular, cellular, and biomechanical mechanisms that couple musculoskeletal form and function during development and evolution.}, } @article {pmid29753444, year = {2018}, author = {Hatala, KG and Perry, DA and Gatesy, SM}, title = {A biplanar X-ray approach for studying the 3D dynamics of human track formation.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {104-118}, doi = {10.1016/j.jhevol.2018.03.006}, pmid = {29753444}, issn = {1095-8606}, abstract = {Recent discoveries have made hominin tracks an increasingly prevalent component of the human fossil record, and these data have the capacity to inform long-standing debates regarding the biomechanics of hominin locomotion. However, there is currently no consensus on how to decipher biomechanical variables from hominin tracks. These debates can be linked to our generally limited understanding of the complex interactions between anatomy, motion, and substrate that give rise to track morphology. These interactions are difficult to study because direct visualization of the track formation process is impeded by foot and substrate opacity. To address these obstacles, we developed biplanar X-ray and computer animation methods, derived from X-ray Reconstruction of Moving Morphology (XROMM), to analyze the 3D dynamics of three human subjects' feet as they walked across four substrates (three deformable muds and rigid composite panel). By imaging and reconstructing 3D positions of external markers, we quantified the 3D dynamics at the foot-substrate interface. Foot shape, specifically heel and medial longitudinal arch deformation, was significantly affected by substrate rigidity. In deformable muds, we found that depths measured across tracks did not directly reflect the motions of the corresponding regions of the foot, and that track outlines were not perfectly representative of foot size. These results highlight the complex, dynamic nature of track formation, and the experimental methods presented here offer a promising avenue for developing and refining methods for accurately inferring foot anatomy and gait biomechanics from fossil hominin tracks.}, } @article {pmid29753443, year = {2018}, author = {Williams, SA}, title = {Was the last common ancestor aping a chimp or just monkeying around?.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {72-74}, doi = {10.1016/j.jhevol.2018.04.007}, pmid = {29753443}, issn = {1095-8606}, } @article {pmid29753442, year = {2018}, author = {de la Torre, I and McHenry, L and Njau, J}, title = {From the Oldowan to the Acheulean at Olduvai Gorge, Tanzania - An introduction to the special issue.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {1-6}, doi = {10.1016/j.jhevol.2018.03.012}, pmid = {29753442}, issn = {1095-8606}, } @article {pmid29753441, year = {2018}, author = {Blegen, N and Jicha, BR and McBrearty, S}, title = {A new tephrochronology for early diverse stone tool technologies and long-distance raw material transport in the Middle to Late Pleistocene Kapthurin Formation, East Africa.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {75-103}, doi = {10.1016/j.jhevol.2018.03.005}, pmid = {29753441}, issn = {1095-8606}, abstract = {The Middle to Late Pleistocene (780-10 ka) of East Africa records evidence of significant behavioral change, early fossils of Homo sapiens, and the dispersals of our species across and out of Africa. Studying human evolution in this time period thus requires an extensive and precise chronology relating behavioral evidence from archaeological sequences to aspects of hominin biology and evidence of past environments from fossils and geological sequences. Tephrochronology provides the chronostratigraphic resolution to achieve this through correlation and dating of volcanic ashes. The tephrochronology of the Kapthurin Formation presented here, based on tephra correlations and 40Ar/39Ar dates, provides new ages between 395.6 ± 3.5 ka and 465.3 ± 1.0 ka for nine sites showing diverse blade and Levallois methods of core reduction. These are >110 kyr older than previously known in East Africa. New 40Ar/39Ar dates provide a refined age of 222.5 ± 0.6 ka for early evidence of long-distance (166 km) obsidian transport at the Sibilo School Road Site. A tephra correlation between the Baringo and Victoria basins also provides a new date of ∼100 ka for the Middle Stone Age site of Keraswanin. By providing new and older dates for 11 sites containing several important aspects of hominin behavior and extending the chronology of the Kapthurin Formation forward by ∼130,000 years, the tephrochronology presented here contributes one of the longest and most refined chronostratigraphic frameworks of Middle through Late Pleistocene East Africa. This tephrochronology thus provides the foundation to understand the process of modern human behavioral evolution as it relates to biological and paleoenvironmental circumstances.}, } @article {pmid29753324, year = {2018}, author = {Connerton, PL and Richards, PJ and Lafontaine, GM and O'Kane, PM and Ghaffar, N and Cummings, NJ and Smith, DL and Fish, NM and Connerton, IF}, title = {The effect of the timing of exposure to Campylobacter jejuni on the gut microbiome and inflammatory responses of broiler chickens.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {88}, pmid = {29753324}, issn = {2049-2618}, mesh = {Animals ; Campylobacter Infections/*immunology/microbiology ; Campylobacter jejuni/immunology/*isolation & purification ; Cecum/*microbiology ; Chemokines/metabolism ; Chickens ; Food Safety ; Gastrointestinal Microbiome/*immunology ; Inflammation/immunology ; Intestinal Mucosa/*immunology/*microbiology ; Male ; Poultry Diseases/*immunology/microbiology ; Th17 Cells/immunology ; }, abstract = {BACKGROUND: Campylobacters are an unwelcome member of the poultry gut microbiota in terms of food safety. The objective of this study was to compare the microbiota, inflammatory responses, and zootechnical parameters of broiler chickens not exposed to Campylobacter jejuni with those exposed either early at 6 days old or at the age commercial broiler chicken flocks are frequently observed to become colonized at 20 days old.

RESULTS: Birds infected with Campylobacter at 20 days became cecal colonized within 2 days of exposure, whereas birds infected at 6 days of age did not show complete colonization of the sample cohort until 9 days post-infection. All birds sampled thereafter were colonized until the end of the study at 35 days (mean 6.1 log10 CFU per g of cecal contents). The cecal microbiota of birds infected with Campylobacter were significantly different to age-matched non-infected controls at 2 days post-infection, but generally, the composition of the cecal microbiota were more affected by bird age as the time post infection increased. The effects of Campylobacter colonization on the cecal microbiota were associated with reductions in the relative abundance of OTUs within the taxonomic family Lactobacillaceae and the Clostridium cluster XIVa. Specific members of the Lachnospiraceae and Ruminococcaceae families exhibit transient shifts in microbial community populations dependent upon the age at which the birds become colonized by C. jejuni. Analysis of ileal and cecal chemokine/cytokine gene expression revealed increases in IL-6, IL-17A, and Il-17F consistent with a Th17 response, but the persistence of the response was dependent on the stage/time of C. jejuni colonization that coincide with significant reductions in the abundance of Clostridium cluster XIVa.

CONCLUSIONS: This study combines microbiome data, cytokine/chemokine gene expression with intestinal villus, and crypt measurements to compare chickens colonized early or late in the rearing cycle to provide insights into the process and outcomes of Campylobacter colonization. Early colonization results in a transient growth rate reduction and pro-inflammatory response but persistent modification of the cecal microbiota. Late colonization produces pro-inflammatory responses with changes in the cecal microbiota that will endure in market-ready chickens.}, } @article {pmid29753018, year = {2018}, author = {Davis, JA and Koenig, AL and Lubert, A and Chestnut, B and Liu, F and Palencia Desai, S and Winkler, T and Pociute, K and Choi, K and Sumanas, S}, title = {ETS transcription factor Etsrp / Etv2 is required for lymphangiogenesis and directly regulates vegfr3 / flt4 expression.}, journal = {Developmental biology}, volume = {440}, number = {1}, pages = {40-52}, pmid = {29753018}, issn = {1095-564X}, support = {R21 AI128445/AI/NIAID NIH HHS/United States ; T32 HL125204/HL/NHLBI NIH HHS/United States ; R01 HL107369/HL/NHLBI NIH HHS/United States ; R01 HL055337/HL/NHLBI NIH HHS/United States ; F31 HL135986/HL/NHLBI NIH HHS/United States ; R01 HL063736/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Embryo, Nonmammalian ; Embryonic Stem Cells ; Endothelial Cells/metabolism ; Gene Expression Regulation, Developmental/genetics ; HEK293 Cells ; Humans ; Lymphangiogenesis/genetics/*physiology ; Lymphatic Vessels/embryology/metabolism ; Mice ; Morpholinos/metabolism ; Signal Transduction ; Transcription Factors/genetics/physiology ; Vascular Endothelial Growth Factor C/genetics ; Vascular Endothelial Growth Factor Receptor-3/genetics ; Zebrafish ; Zebrafish Proteins/*genetics/*physiology ; }, abstract = {The molecular mechanisms initiating the formation of the lymphatic system, lymphangiogenesis, are still poorly understood. Here we have identified a novel role in lymphangiogenesis for an ETS transcription factor, Etv2/Etsrp, a known regulator of embryonic vascular development. Through the use of fully validated photoactivatable morpholinos we show that inducible Etv2 inhibition in zebrafish embryos at 1 day post-fertilization (dpf) results in significant inhibition of lymphangiogenesis, while development of blood vessels is unaffected. In Etv2-inhibited embryos and larvae, the number of lymphatic progenitors is greatly reduced, the major lymphatic vessel, the thoracic duct, is absent or severely fragmented, and lymphangiogenesis-associated marker expression, including lyve1b, prox1a, and vegfr3/flt4, is strongly downregulated. We also demonstrate that lymphatic progenitors in Etv2 deficient embryos fail to respond to Vegfc signaling. Chromatin immunoprecipitation and sequencing (ChIP-Seq) studies using differentiated mouse embryonic stem (ES) cells as well as luciferase reporter studies in the ES cells and in zebrafish embryos argue that Etv2 directly binds the promoter/enhancer regions of Vegfc receptor Vegfr3/Flt4 and lymphatic marker Lyve1, and promotes their expression. Together these data support a model where Etv2 initiates lymphangiogenesis by directly promoting the expression of flt4 within the posterior cardinal vein.}, } @article {pmid29753017, year = {2018}, author = {Vaufrey, L and Balducci, C and Lafont, R and Prigent, C and Le Bras, S}, title = {Size matters! Aurora A controls Drosophila larval development.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {88-98}, doi = {10.1016/j.ydbio.2018.05.005}, pmid = {29753017}, issn = {1095-564X}, mesh = {Animals ; Aurora Kinase A/genetics/metabolism/*physiology ; Brain/metabolism ; Cell Cycle Proteins/metabolism ; Cell Differentiation ; Cell Division/physiology ; Drosophila/*embryology/metabolism ; Drosophila Proteins/genetics/metabolism/*physiology ; Genetic Pleiotropy/genetics ; Larva/*metabolism/physiology ; Loss of Function Mutation/genetics ; Neural Stem Cells/metabolism ; Neurogenesis/physiology ; Neurons/metabolism ; Protein-Serine-Threonine Kinases/genetics/physiology ; Spindle Apparatus/metabolism ; }, abstract = {In metazoans, organisms arising from a fertilized egg, the embryo will develop through multiple series of cell divisions, both symmetric and asymmetric, leading to differentiation. Aurora A is a serine threonine kinase highly involved in such divisions. While intensively studied at the cell biology level, its function in the development of a whole organism has been neglected. Here we investigated the pleiotropic effect of Aurora A loss-of-function in Drosophila larval early development. We report that Aurora A is required for proper larval development timing control through direct and indirect means. In larval tissues, Aurora A is required for proper symmetric division rate and eventually development speed as we observed in central brain, wing disc and ring gland. Moreover, Aurora A inactivation induces a reduction of ecdysteroids levels and a pupariation delay as an indirect consequence of ring gland development deceleration. Finally, although central brain development is initially restricted, we confirmed that brain lobe size eventually increases due to additive phenotypes: delayed pupariation and over-proliferation of cells with an intermediate cell-identity between neuroblast and ganglion mother cell resulting from defective asymmetric neuroblast cell division.}, } @article {pmid29753016, year = {2018}, author = {Kline, A and Curry, T and Lewellyn, L}, title = {The Misshapen kinase regulates the size and stability of the germline ring canals in the Drosophila egg chamber.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {99-112}, pmid = {29753016}, issn = {1095-564X}, support = {P40 OD018537/OD/NIH HHS/United States ; R15 HD084243/HD/NICHD NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/metabolism ; Actins/metabolism ; Animals ; Contractile Proteins/metabolism ; Drosophila/genetics/metabolism ; Drosophila Proteins/genetics/*metabolism/*physiology ; Female ; Germ Cells/cytology/metabolism/*physiology ; Microfilament Proteins/metabolism ; Oocytes/cytology/enzymology ; Oogenesis/physiology ; Protein-Serine-Threonine Kinases/genetics/*metabolism/*physiology ; }, abstract = {Intercellular bridges are conserved structures that allow neighboring cells to exchange cytoplasmic material; defects in intercellular bridges can lead to infertility in many organisms. Here, we use the Drosophila egg chamber to study the mechanisms that regulate intercellular bridges. Within the developing egg chamber, the germ cells (15 nurse cells and 1 oocyte) are connected to each other through intercellular bridges called ring canals, which expand over the course of oogenesis to support the transfer of materials from the nurse cells to the oocyte. The ring canals are enriched in actin and actin binding proteins, and many proteins have been identified that localize to the germline ring canals and control their expansion and stability. Here, we demonstrate a novel role for the Ste20 family kinase, Misshapen (Msn), in regulation of the size of the germline ring canals. Msn localizes to ring canals throughout most of oogenesis, and depletion of Msn led to the formation of larger ring canals. Over-expression of Msn decreased ring canal diameter, and expression of a membrane tethered form of Msn caused ring canal detachment and nurse cell fusion. Altering the levels or localization of Msn also led to changes in the actin cytoskeleton and altered the localization of E-cadherin, which suggests that Msn could be indirectly limiting ring canal size by altering the structure or dynamics of the actin cytoskeleton and/or adherens junctions.}, } @article {pmid29752987, year = {2018}, author = {Wittorf, L and Jones, CM and Bonilla-Rosso, G and Hallin, S}, title = {Expression of nirK and nirS genes in two strains of Pseudomonas stutzeri harbouring both types of NO-forming nitrite reductases.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {343-347}, doi = {10.1016/j.resmic.2018.04.010}, pmid = {29752987}, issn = {1769-7123}, mesh = {Cytochromes/*genetics/*metabolism ; Denitrification/genetics/*physiology ; Gene Expression Regulation/*genetics ; Nitrates/chemistry ; Nitric Oxide/*biosynthesis ; Nitrite Reductases/*genetics/*metabolism ; Nitrites/chemistry ; Oxidation-Reduction ; Oxygen/chemistry ; Pseudomonas stutzeri/*genetics/*metabolism ; Trans-Activators/genetics/metabolism ; }, abstract = {Reduction of nitrite to nitric oxide in denitrification is catalysed by two different nitrite reductases, encoded by nirS or nirK. Long considered mutually exclusive and functionally redundant in denitrifying bacteria, we show expression of both genes co-occurring in Pseudomonas stutzeri. The differential expression patterns between strain AN10 and JM300 in relation to oxygen and nitrate and their different denitrification phenotypes, with AN10 reducing nitrate more rapidly and accumulating nitrite, suggest that nirS and nirK can have different roles. Dissimilar gene arrangements and transcription factors in the nir gene neighbourhoods could explain the observed differences in gene expression and denitrification activity.}, } @article {pmid29752677, year = {2018}, author = {Dos Santos, A and Campagnari, F and Krepischi, ACV and Ribeiro Câmara, ML and de Arruda Brasil, RCE and Vieira, L and Vianna-Morgante, AM and Otto, PA and Pearson, PL and Rosenberg, C}, title = {Insight into the mechanisms and consequences of recurrent telomere capture associated with a sub-telomeric deletion.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {}, number = {}, pages = {}, pmid = {29752677}, issn = {1573-6849}, support = {130185/2014-0//Brazilian National Council for Scientific and Technological Development (CNPq)/ ; 306879/2014-0//Brazilian National Council for Scientific and Technological Development (CNPq)/ ; 2012/50981-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2013/08028-1//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, abstract = {A complex mosaicism of the short arm of chromosome 1 detected by SNP microarray analysis is described in a patient presenting a 4-Mb 1p36 terminal deletion and associated phenotypic features. The array pattern of chromosome 1p displayed an intriguing increase in divergence of the SNP heterozygote frequency from the expected 50% from the centromere towards the 1p36 breakpoint. This suggests that various overlapping segments of UPD were derived by somatic recombination between the 1p homologues. The most likely explanation was the occurrence of a series of events initiated in either a gamete or an early embryonic cell division involving a 1pter deletion rapidly followed by multiple telomere captures, resulting in additive, stepped increases in frequency of homozygosity towards the telomere. The largest segment involved the entire 1p, and at least four other capture events were observed, indicating that at least five independent telomere captures occurred in separate cell lineages. The determination of breakpoint position by detection of abrupt changes in B-allele frequency using a moving window analysis demonstrated that they were identical in blood and saliva, the tissues available for analysis. We developed a model to explain the interaction of parameters determining the mosaic clones and concluded that, while number, size, and position of telomere captures were important initiating determinants, variation in individual clone frequencies was the main contributor to mosaic differences between tissues. All previous reports of telomere capture have been restricted to single events. Other cases involving multiple telomere capture probably exist but require investigation by SNP microarrays for their detection.}, } @article {pmid29752494, year = {2018}, author = {Zhang, X and Ma, Y and Ye, G}, title = {Morphological Observation and Comparative Transcriptomic Analysis of Clostridium perfringens Biofilm and Planktonic Cells.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29752494}, issn = {1432-0991}, support = {31460672, 31760739//National Natural Science Foundation Programs of China/ ; }, abstract = {Bacterial biofilms can enhance survival in adverse environments and promote infection. However, little is known about biofilm formation by Clostridium perfringens. To better characterize this process, we used SEM to observe the surfaces of C. perfringens biofilms after 12, 24, 48, and 72 h of incubation. Biofilm cells appeared to be encased in a dense matrix material, and the total biomass of the biofilm increased with incubation time. To gain insight into the differentially expressed genes (DEGs) between biofilm and planktonic cells, we carried out comparative transcriptomic analysis using RNA sequencing. In total, 91 genes were significantly differentially expressed, with 40 being up-regulated and 51 down-regulated. In particular, genes encoding sortase, ribosomal proteins, and ATP synthase were up-regulated in biofilms, while genes coding for clostripain and phospholipase C were down-regulated. To validate the RNA sequencing results, qRT-PCR analysis was performed using five randomly selected DEGs. Results showed that all five genes were up-regulated, which was in accordance with the RNA sequencing results. To examine the functional differences, the DEGs were characterized by GO and KEGG pathway enrichment analyses. Results showed that the up-regulated genes were divided into 32 significantly enriched GO terms, with "macromolecular complex" being the most common. Oxidative phosphorylation was the only significantly enriched pathway, suggesting that ATP is required for biofilm stability. This study provides valuable insights into the morphology and transcriptional regulation of C. perfringens during biofilm formation, and will be useful for understanding and developing biofilm-based processes.}, } @article {pmid29752465, year = {2018}, author = {Du Toit, A}, title = {Bait for phages.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {394}, doi = {10.1038/s41579-018-0028-x}, pmid = {29752465}, issn = {1740-1534}, } @article {pmid29752464, year = {2018}, author = {Du Toit, A}, title = {How to signal to your neighbours.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {394}, doi = {10.1038/s41579-018-0026-z}, pmid = {29752464}, issn = {1740-1534}, } @article {pmid29752453, year = {2018}, author = {Resplandy, L}, title = {Will ocean zones with low oxygen levels expand or shrink?.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {314-315}, doi = {10.1038/d41586-018-05034-y}, pmid = {29752453}, issn = {1476-4687}, mesh = {Animals ; Atmosphere/chemistry ; Ecosystem ; Feedback ; *Global Warming ; Oceans and Seas ; Oxygen/*analysis ; Seawater/*analysis/*chemistry ; Solubility ; Temperature ; Tropical Climate ; }, } @article {pmid29752452, year = {2018}, author = {Savelli, F and Knierim, JJ}, title = {AI mimics brain codes for navigation.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {313-314}, doi = {10.1038/d41586-018-04992-7}, pmid = {29752452}, issn = {1476-4687}, mesh = {Artificial Intelligence ; Brain/*physiology ; Brain Mapping ; Humans ; }, } @article {pmid29752451, year = {2018}, author = {Lim, L and Marín, O}, title = {More than one way to induce a neuron.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {316-317}, doi = {10.1038/d41586-018-04978-5}, pmid = {29752451}, issn = {1476-4687}, mesh = {*Cell Differentiation ; *Neurons ; }, } @article {pmid29752449, year = {2018}, author = {Krumm, B and Roth, BL}, title = {Activation mechanisms for a universal signalling protein.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {318-319}, doi = {10.1038/d41586-018-04977-6}, pmid = {29752449}, issn = {1476-4687}, mesh = {*Signal Transduction ; }, } @article {pmid29752383, year = {2018}, author = {Nelson, P and Masel, J}, title = {Reply to Cheong et al.: Unicellular survival precludes Parrondo's paradox.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5260}, doi = {10.1073/pnas.1806709115}, pmid = {29752383}, issn = {1091-6490}, mesh = {*Cell Survival ; *Cellular Senescence ; }, } @article {pmid29752382, year = {2018}, author = {Proulx, CD and Aronson, S and Milivojevic, D and Molina, C and Loi, A and Monk, B and Shabel, SJ and Malinow, R}, title = {A neural pathway controlling motivation to exert effort.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5792-5797}, pmid = {29752382}, issn = {1091-6490}, support = {R01 MH091119/MH/NIMH NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Animals ; Depression ; Habenula/*physiology ; Humans ; Motivation/*physiology ; Movement/physiology ; Neural Pathways/*physiology ; Optogenetics ; Photometry ; Rats ; Task Performance and Analysis ; Tegmentum Mesencephali/*physiology ; }, abstract = {The neural mechanisms conferring reduced motivation, as observed in depressed individuals, is poorly understood. Here, we examine in rodents if reduced motivation to exert effort is controlled by transmission from the lateral habenula (LHb), a nucleus overactive in depressed-like states, to the rostromedial tegmental nucleus (RMTg), a nucleus that inhibits dopaminergic neurons. In an aversive test wherein immobility indicates loss of effort, LHb→RMTg transmission increased during transitions into immobility, driving LHb→RMTg increased immobility, and inhibiting LHb→RMTg produced the opposite effects. In an appetitive test, driving LHb→RMTg reduced the effort exerted to receive a reward, without affecting the reward's hedonic property. Notably, LHb→RMTg stimulation only affected specific aspects of these motor tasks, did not affect all motor tasks, and promoted avoidance, indicating that LHb→RMTg activity does not generally reduce movement but appears to carry a negative valence that reduces effort. These results indicate that LHb→RMTg activity controls the motivation to exert effort and may contribute to the reduced motivation in depression.}, } @article {pmid29752381, year = {2018}, author = {Guo, Z and He, J and Barry, BA}, title = {Calcium, conformational selection, and redox-active tyrosine YZ in the photosynthetic oxygen-evolving cluster.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5658-5663}, pmid = {29752381}, issn = {1091-6490}, mesh = {Calcium/*chemistry/metabolism ; Oxidation-Reduction ; Oxygen/*chemistry/metabolism ; Photosynthesis ; Photosystem II Protein Complex/*chemistry/metabolism ; Protein Conformation ; Spectroscopy, Fourier Transform Infrared ; Tyrosine/*chemistry/metabolism ; Water ; }, abstract = {In Photosystem II (PSII), YZ (Tyr161D1) participates in radical transfer between the chlorophyll donor and the Mn4CaO5 cluster. Under flashing illumination, the metal cluster cycles among five Sn states, and oxygen is evolved from water. The essential YZ is transiently oxidized and reduced on each flash in a proton-coupled electron transfer (PCET) reaction. Calcium is required for function. Of reconstituted divalent ions, only strontium restores oxygen evolution. YZ is predicted to hydrogen bond to calcium-bound water and to His190D1 in PSII structures. Here, we report a vibrational spectroscopic study of YZ radical and singlet in the presence of the metal cluster. The S2 state is trapped by illumination at 190 K; flash illumination then generates the S2YZ radical. Using reaction-induced FTIR spectroscopy and divalent ion depletion/substitution, we identify calcium-sensitive tyrosyl radical and tyrosine singlet bands in the S2 state. In calcium-containing PSII, two CO stretching bands are detected at 1,503 and 1,478 cm-1 These bands are assigned to two different radical conformers in calcium-containing PSII. At pH 6.0, the 1,503-cm-1 band shifts to 1,507 cm-1 in strontium-containing PSII, and the band is reduced in intensity in calcium-depleted PSII. These effects are consistent with a hydrogen-bonding interaction between the calcium site and one conformer of radical YZ. Analysis of the amide I region indicates that calcium selects for a PCET reaction in a subset of the YZ conformers, which are trapped in the S2 state. These results support the interpretation that YZ undergoes a redox-coupled conformational change, which is calcium dependent.}, } @article {pmid29752380, year = {2018}, author = {Cheong, KH and Koh, JM and Jones, MC}, title = {Multicellular survival as a consequence of Parrondo's paradox.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {23}, pages = {E5258-E5259}, doi = {10.1073/pnas.1806485115}, pmid = {29752380}, issn = {1091-6490}, mesh = {*Cell Survival ; *Cellular Senescence ; }, } @article {pmid29752168, year = {2018}, author = {da Costa, RR and Poulsen, M}, title = {Mixed-Mode Transmission Shapes Termite Gut Community Assemblies.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {557-559}, doi = {10.1016/j.tim.2018.04.005}, pmid = {29752168}, issn = {1878-4380}, abstract = {Understanding how microbial symbiont community assemblies are shaped over evolutionary time is challenging. The current state of the art involves exploring similarities and differences in communities within and between host species, often aiming to link these to host ecology and evolution. However, this masks the evolutionary histories of individual bacterial lineages.}, } @article {pmid29752147, year = {2018}, author = {Rea, E and Le Roch, KG and Tewari, R}, title = {Sex in Plasmodium falciparum: Silence Play between GDV1 and HP1.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {450-452}, pmid = {29752147}, issn = {1471-5007}, support = {R01 AI106775/AI/NIAID NIH HHS/United States ; R01 AI136511/AI/NIAID NIH HHS/United States ; G0900109//Medical Research Council/United Kingdom ; G0900278//Medical Research Council/United Kingdom ; MR/K011782/1//Medical Research Council/United Kingdom ; BB/N017609/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Chromosomal Proteins, Non-Histone ; Malaria, Falciparum/parasitology ; *Plasmodium falciparum ; }, abstract = {Understanding how malaria parasites commit to sexual development is key to the development of transmission-blocking strategies. Recent work by Filarsky and colleagues extends our understanding of the molecular mechanisms driving this process by characterizing an early factor in gametocytogenesis, and showing how this fits neatly into our current knowledge of sexual commitment.}, } @article {pmid29752005, year = {2018}, author = {Uno, KT and Rivals, F and Bibi, F and Pante, M and Njau, J and de la Torre, I}, title = {Large mammal diets and paleoecology across the Oldowan-Acheulean transition at Olduvai Gorge, Tanzania from stable isotope and tooth wear analyses.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {76-91}, doi = {10.1016/j.jhevol.2018.01.002}, pmid = {29752005}, issn = {1095-8606}, abstract = {The well-dated Pleistocene sediments at Olduvai Gorge have yielded a rich record of hominin fossils, stone tools, and vertebrate faunal remains that, taken together, provide insight to hominin behavior and paleoecology. Since 2008, the Olduvai Geochronology and Archaeology Project (OGAP) has undertaken extensive excavations in Bed II that have yielded a large collection of early Pleistocene stone tools and fossils. The strata of Lower, Middle and Upper Bed II at Olduvai Gorge capture the critical transition from Oldowan to Acheulean technology and therefore provide an opportunity to explore the possible role of biotic and abiotic change during the transition. Here, we analyze newly discovered and existing fossil teeth from Bed II sites using stable isotope and tooth wear methods to investigate the diets of large mammals. We reconstruct the dietary ecology of Bed II mammals and evaluate whether vegetation or hydroclimate shifts are associated with the technological change. Combined isotope and tooth wear data suggest most mammals were C4 grazers or mixed feeders. Carbon isotope data from bulk enamel samples indicate that a large majority of Bed II large mammals analyzed had diets comprising mostly C4 vegetation (>75% of diet), whereas only a small number of individuals had either mixed C3-C4 or mostly C3 diets (<25% C4). Mesowear generally indicates an increase of the abrasiveness of the diet between intervals IIA and IIB (∼1.66 Ma), probably reflecting increased grazing. Microwear indicates more abrasive diets in interval IIA suggesting stronger seasonal differences at the time of death during this interval. This is also supported by the intratooth isotope profiles from Equus oldowayensis molars, which suggest a possible decrease in seasonality across the transition. Neither stable isotope nor tooth wear analyses indicate major vegetation or hydrological change across the Oldowan-Acheulean transition.}, } @article {pmid29752004, year = {2018}, author = {Proffitt, T}, title = {Is there a Developed Oldowan A at Olduvai Gorge? A diachronic analysis of the Oldowan in Bed I and Lower-Middle Bed II at Olduvai Gorge, Tanzania.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {92-113}, doi = {10.1016/j.jhevol.2018.01.006}, pmid = {29752004}, issn = {1095-8606}, abstract = {Debates regarding the validity of the Developed Oldowan as separate cultural facies within the Oldowan techno-complex have primarily concentrated on the Developed Oldowan B/Acheulean transition, with little attention paid to the validity of the Developed Oldowan A (DOA) as a valid technological differentiation. This study presents a diachronic technological analysis and comparison of Oldowan and DOA lithic assemblages from Olduvai Gorge, Tanzania, dated between 1.84 and 1.6 Ma, to test the validity of Leakey's original distinction between these two cultural facies. The results from this comparative analysis show very few technological differences between the lithic assemblages previously assigned to the DOA and Classic Oldowan. Significant diachronic variation in raw material availability and use is, however, identified between Bed I and Lower/Middle Bed II of Olduvai Gorge, which may go some way to explaining the originally perceived techno-cultural differences. The results suggest an increase in hominin knapping and percussive activities, as well as a clear ability to preferentially select high quality raw materials stratigraphically above Tuff IF. Technological innovation and complexity, however, does not seem to vary significantly between the Classic Oldowan and DOA assemblages. The results of this analysis along with similar studies from the wider eastern African region lead to the conclusion that the term Developed Oldowan A should no longer be used.}, } @article {pmid29751844, year = {2018}, author = {Kahsay, AG and Hagos, DG and Abay, GK and Mezgebo, TA}, title = {Prevalence and antimicrobial susceptibility patterns of methicillin-resistant Staphylococcus aureus among janitors of Mekelle University, North Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {294}, pmid = {29751844}, issn = {1756-0500}, support = {CRPO/CHS/015/08//Mekelle University, College of Health Sciences/ ; }, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/*pharmacology ; *Drug Resistance, Bacterial ; Ethiopia/epidemiology ; Female ; Health Personnel/*statistics & numerical data ; Hospitals, University/*statistics & numerical data ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus/drug effects/*isolation & purification ; Microbial Sensitivity Tests/statistics & numerical data ; Prevalence ; Staphylococcal Infections/*epidemiology/*microbiology ; Staphylococcus aureus/drug effects/*isolation & purification ; Young Adult ; }, abstract = {OBJECTIVE: The objective of this study was to determine the prevalence of methicillin-resistant Staphylococcus aureus and antimicrobial susceptibility patterns among janitors working at Mekelle University, Tigray, Northern Ethiopia.

RESULT: The overall prevalence of S. aureus and MRSA in the present study were 17.97% (69/384) and 6.25% (24/384) respectively. Although not statistically significant, the prevalence of MRSA among janitors working in the medical area (9.7%, 10/103) was two times higher than the non-medical area (4.9%, 14/281). Janitors who had more service year and who were unable to read and write were found with high isolates of MRSA. Nasal carriage of MRSA among janitors who work in the hospital and who were hospitalized in the last 3 months and those who had exposure to wastes and body fluids were 13 (37.1%) and 10 (38.5%) respectively. Majority of the isolates of S. aureus were sensitive to ciprofloxacin (67; 97%), doxycycline (56; 81%), erythromycin (54; 78%), chloramphenicol (50; 72.5%) and cefoxitin (45; 65.2%). Sixty-seven of the 69 (97%) were resistant to penicillin. Of the 69 isolates of S. aureus, 22 (31.9%) showed multidrug resistant. Fourteen were resistant to three antimicrobials, 2 were resistant to four antimicrobials, and 7 were resistant to five antimicrobials.}, } @article {pmid29751841, year = {2018}, author = {Tewabe, T and Kindie, S}, title = {Level of insulin adherence among diabetes mellitus patients in Felege Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia, 2017: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {295}, pmid = {29751841}, issn = {1756-0500}, support = {1//Bahir Dar University/ ; }, mesh = {Adult ; Cross-Sectional Studies ; Diabetes Mellitus/*drug therapy/epidemiology ; Ethiopia/epidemiology ; Female ; Hospitals/*statistics & numerical data ; Humans ; Male ; Medication Adherence/*statistics & numerical data ; Middle Aged ; }, abstract = {OBJECTIVES: The objective of this study was to know the level of insulin adherence and to identify factors affecting insulin adherence among diabetes mellitus patients in Felege Hiwot Referral Hospital, Bahir Dar, Northwest Ethiopia.

RESULTS: Prevalence of insulin adherence was 59.2%. Patients who are married [AOR = 0.3 (0.14-0.7)], have regular health care visit [AOR = 3.3 (1.5-7.5)] and accessing insulin with low cost [AOR = 2.9 (1.3-6.3)] were more likely to adhere insulin therapy than their counterparts. Recommendations to increase insulin adherence were: government and non-governmental organizations, volunteers and concerned bodies should support syringe and needles for diabetes patients, health care providers and responsible bodies should give intensive health education about the effect of stopping insulin medication.}, } @article {pmid29751830, year = {2018}, author = {Lim, ES and Rodriguez, C and Holtz, LR}, title = {Amniotic fluid from healthy term pregnancies does not harbor a detectable microbial community.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {87}, pmid = {29751830}, issn = {2049-2618}, support = {2017076/DDCF/Doris Duke Charitable Foundation/United States ; MD-FR-2013-292//Children's Discovery Institute/International ; BOC 388999//March of Dimes Foundation/International ; UL1TR000448/TR/NCATS NIH HHS/United States ; R00 DK107923/NH/NIH HHS/United States ; R00 DK107923/DK/NIDDK NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Amniotic Fluid/*microbiology/*virology ; Bacteria/*classification/genetics/isolation & purification ; Body Fluids/*microbiology/*virology ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Microbiota/*genetics ; Pregnancy ; Viruses/*classification/genetics/isolation & purification ; }, abstract = {Recent studies have conflicting data regarding the presence of intra-amniotic microbiota. Viral communities are increasingly recognized as important although overlooked components of the human microbiota. It is unknown if the developing fetus is exposed to a community of viruses (virome). Given the debate over the existence of an intra-amniotic microbial community and the importance of understanding how the infant gut is populated, we characterized the virome and bacterial microbiota of amniotic fluid from 24 uncomplicated term pregnancies using next-generation sequencing methods. Contrary to expectations, the bacterial microbiota of amniotic fluid was indistinguishable from contamination controls. Viral reads were sparse in the amniotic fluid, and we found no evidence of a core viral community across samples.}, } @article {pmid29751818, year = {2018}, author = {Muthukrishnan, S and Puri, M}, title = {Harnessing the evolutionary information on oxygen binding proteins through Support Vector Machines based modules.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {290}, pmid = {29751818}, issn = {1756-0500}, mesh = {Animals ; *Biological Evolution ; Carrier Proteins/*metabolism ; Hemeproteins/*metabolism ; Hemerythrin/*metabolism ; Hemocyanins/*metabolism ; Oxygen/*metabolism ; *Support Vector Machine ; }, abstract = {OBJECTIVES: The arrival of free oxygen on the globe, aerobic life is becoming possible. However, it has become very clear that the oxygen binding proteins are widespread in the biosphere and are found in all groups of organisms, including prokaryotes, eukaryotes as well as in fungi, plants, and animals. The exponential growth and availability of fresh annotated protein sequences in the databases motivated us to develop an improved version of "Oxypred" for identifying oxygen-binding proteins.

RESULTS: In this study, we have proposed a method for identifying oxy-proteins with two different sequence similarity cutoffs 50 and 90%. A different amino acid composition based Support Vector Machines models was developed, including the evolutionary profiles in the form position-specific scoring matrix (PSSM). The fivefold cross-validation techniques were applied to evaluate the prediction performance. Also, we compared with existing methods, which shows nearly 97% recognition, but, our newly developed models were able to recognize almost 99.99 and 100% in both oxy-50 and 90% similarity models respectively. Our result shows that our approaches are faster and achieve a better prediction performance over the existing methods. The web-server Oxypred2 was developed for an alternative method for identifying oxy-proteins with more additional modules including PSSM, available at http://bioinfo.imtech.res.in/servers/muthu/oxypred2/home.html .}, } @article {pmid29751813, year = {2018}, author = {Ajong, AB and Kenfack, B and Agbor, VN and Njotang, PN}, title = {Ruptured caesarean scar ectopic pregnancy: a diagnostic dilemma in a resource-limited setting.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {292}, pmid = {29751813}, issn = {1756-0500}, mesh = {Adult ; Cicatrix/*diagnosis/surgery ; Female ; Hemoperitoneum/*diagnosis/surgery ; Humans ; Pregnancy ; Pregnancy, Ectopic/*diagnosis/surgery ; Uterine Rupture/*diagnosis/surgery ; }, abstract = {BACKGROUND: Caesarean scar pregnancy (CSP) remains a very rare form of ectopic pregnancy associated with serious life threatening obstetric complications and even death in case of late diagnosis and treatment.

CASE PRESENTATION: We report a case of a ruptured caesarean scar pregnancy in a 29 year-old gravida 5, para 3 with a past obstetric history of two consecutive caesarean sections done 9 and 5 years ago respectively. The patient presented with intermittent lower abdominal pains on a 20 weeks gestation associated with mild epigastralgia and 2 previous episodes of mild pervaginal bleeding (2 and 1 months ago respectively before consultation) managed with injectable progesterone. Her evolution 4 h later was marked by an increase in the intensity of the abdominal pain, an unmeasurable blood pressure and a feeble pulse. Immediate paracentesis revealed 10 cc of fresh non coagulating blood. The diagnosis of ruptured ectopic pregnancy with abundant hemoperitoneum was considered and an emergency laparotomy with fluid and blood resuscitation was carried out. A midline laparotomy revealed a ruptured caesarean scar ectopic pregnancy with an abundant hemoperitoneum. Careful resection of the placenta and repair of the ruptured isthmic region of the uterus was carried out. Recovery after surgery was without complications and the patient was discharged on the 6th day following surgery.

CONCLUSION: Caesarean scar pregnancy remains a very rare obstetric condition. Late diagnosis of this condition can be associated with serious life threatening obstetric complications. The rarity of the condition warrants a high index of suspicion among clinicians.}, } @article {pmid29751780, year = {2018}, author = {Niguse, S and Desta, K and Gebremichael, G and Gebrezgeaxier, A and Getahun, M and Kassa, D}, title = {QuantiFERON-TB Gold In-tube test for the diagnosis of active and latent tuberculosis in selected health facilities of Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {293}, pmid = {29751780}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; HIV Infections/epidemiology ; Humans ; Interferon-gamma Release Tests/*standards ; Latent Tuberculosis/blood/diagnosis/epidemiology ; Male ; Middle Aged ; Predictive Value of Tests ; Sensitivity and Specificity ; Tuberculin Test/*standards ; Tuberculosis/blood/*diagnosis/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: To determine the performance of QuantiFERON-TB IN-Gold for the diagnosis active tuberculosis and latent tuberculosis.

RESULTS: A total of 213 participants (136 tuberculosis suspects, 66 latently infected) were enrolled. Of 213, 21 (15.4%) of the tuberculosis suspects and 3 (4.5%) of the latent tuberculosis groups were human immunodeficiency virus infected. The sensitivity, specificity, positive and negative predictive value of QuantiFERON-TB IN-Gold for the diagnosis of active tuberculosis was 70.3% (26/37), 49.5% (49/99), 34.7% (26/75) and 83.1% (49/59) respectively. A kappa value of 0.316 (p = 0.001, 95% CI 1.605-1.609) between QuantiFERON-TB IN-Gold and tuberculin skin test were found.}, } @article {pmid29751778, year = {2018}, author = {Desalegn, DM and Kitila, KT and Balcha, HM and Gebeyehu, CS and Kidan, YW and Amare, K and Dejene, D and Seifu, M and Zewdie, A and Tenna, A and Hailu, TK and Taddese, BD and Bika, AT}, title = {Misdiagnosis of pulmonary tuberculosis and associated factors in peripheral laboratories: a retrospective study, Addis Ababa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {291}, pmid = {29751778}, issn = {1756-0500}, mesh = {*Diagnostic Errors ; Ethiopia ; Humans ; Laboratories/*standards ; Microbiological Techniques/*standards ; Retrospective Studies ; Sputum/*microbiology ; Tuberculosis, Pulmonary/*diagnosis ; }, abstract = {OBJECTIVE: Sputum smear microscopy reading errors are likely to result in failure to detect persons with infectious TB. This study was intended to review misdiagnosis of pulmonary TB and associated factors in peripheral laboratories.

RESULTS: During the study period 1033 (10.5%) sputum smear positive and 8783 (89.5%) smear negative slides were reported by peripheral laboratories. The slides were re-read by the central referral laboratories (CRLs) as the reference standard reading. Of 1033 positive slides reported by peripheral laboratories, 25 (2.4%) were false positive. Out of 8783 smear negative slides reported by peripheral laboratories, 35 (0.4%) were false negative. The sensitivity, specificity, positive predictive value and negative predictive value of peripheral laboratories were 96.64, 99.72, 97.58, and 99.61% respectively. The peripheral laboratories and CRLs have an observed agreement (Po) of 0.9939. Of 135 peripheral laboratories, 93 (68.9%) read negative and positive slides correctly, 49 (36.3%) did not have lens cleaning tissue papers, 11 (8.1%) lacked frosted slides, and 14 (10.4%) had shortage of reagents. As conclusions, the peripheral laboratories and CRLs had high agreement for sputum smear microscopy reading. However, a few TB cases were misdiagnosed despite having the disease; these individuals might continue to spread the infection in the community.}, } @article {pmid29751745, year = {2018}, author = {Krefft, D and Papkov, A and Prusinowski, M and Zylicz-Stachula, A and Skowron, PM}, title = {Randomized DNA libraries construction tool: a new 3-bp 'frequent cutter' TthHB27I/sinefungin endonuclease with chemically-induced specificity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {361}, pmid = {29751745}, issn = {1471-2164}, support = {DS 530-8645-D691-17//University of Gdansk/ ; BMN 538-8645-B048-15/16//University of Gdansk/ ; }, mesh = {Cloning, Molecular ; DNA Cleavage ; Deoxyribonuclease I/*metabolism ; *Gene Library ; Genomics/*methods ; Substrate Specificity ; }, abstract = {BACKGROUND: Acoustic or hydrodynamic shearing, sonication and enzymatic digestion are used to fragment DNA. However, these methods have several disadvantages, such as DNA damage, difficulties in fragmentation control, irreproducibility and under-representation of some DNA segments. The DNA fragmentation tool would be a gentle enzymatic method, offering cleavage frequency high enough to eliminate DNA fragments distribution bias and allow for easy control of partial digests. Only three such frequently cleaving natural restriction endonucleases (REases) were discovered: CviJI, SetI and FaiI. Therefore, we have previously developed two artificial enzymatic specificities, cleaving DNA approximately every ~ 3-bp: TspGWI/sinefungin (SIN) and TaqII/SIN.

RESULTS: In this paper we present the third developed specificity: TthHB27I/SIN(SAM) - a new genomic tool, based on Type IIS/IIC/IIG Thermus-family REases-methyltransferases (MTases). In the presence of dimethyl sulfoxide (DMSO) and S-adenosyl-L-methionine (SAM) or its analogue SIN, the 6-bp cognate TthHB27I recognition sequence 5'-CAARCA-3' is converted into a combined 3.2-3.0-bp 'site' or its statistical equivalent, while a cleavage distance of 11/9 nt is retained. Protocols for various modes of limited DNA digestions were developed.

CONCLUSIONS: In the presence of DMSO and SAM or SIN, TthHB27I is transformed from rare 6-bp cutter to a very frequent one, approximately 3-bp. Thus, TthHB27I/SIN(SAM) comprises a new tool in the very low-represented segment of such prototype REases specificities. Moreover, this modified TthHB27I enzyme is uniquely suited for controlled DNA fragmentation, due to partial DNA cleavage, which is an inherent feature of the Thermus-family enzymes. Such tool can be used for quasi-random libraries generation as well as for other DNA manipulations, requiring high frequency cleavage and uniform distribution of cuts along DNA.}, } @article {pmid29751743, year = {2018}, author = {Cai, Z and Guldbrandtsen, B and Lund, MS and Sahana, G}, title = {Dissecting closely linked association signals in combination with the mammalian phenotype database can identify candidate genes in dairy cattle.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {30}, pmid = {29751743}, issn = {1471-2156}, support = {0603-00519B//Innovation Fund Denmark/ ; }, abstract = {BACKGROUND: Genome-wide association studies (GWAS) have been successfully implemented in cattle research and breeding. However, moving from the associations to identifying the causal variants and revealing underlying mechanisms have proven complicated. In dairy cattle populations, we face a challenge due to long-range linkage disequilibrium (LD) arising from close familial relationships in the studied individuals. Long range LD makes it difficult to distinguish if one or multiple quantitative trait loci (QTL) are segregating in a genomic region showing association with a phenotype. We had two objectives in this study: 1) to distinguish between multiple QTL segregating in a genomic region, and 2) use of external information to prioritize candidate genes for a QTL along with the candidate variant.

RESULTS: We observed fixing the lead SNP as a covariate can help to distinguish additional close association signal(s). Thereafter, using the mammalian phenotype database, we successfully found candidate genes, in concordance with previous studies, demonstrating the power of this strategy. Secondly, we used variant annotation information to search for causative variants in our candidate genes. The variant information successfully identified known causal mutations and showed the potential to pinpoint the causative mutation(s) which are located in coding regions.

CONCLUSIONS: Our approach can distinguish multiple QTL segregating on the same chromosome in a single analysis without manual input. Moreover, utilizing information from the mammalian phenotype database and variant effect predictor as post-GWAS analysis could benefit in candidate genes and causative mutations finding in cattle. Our study not only identified additional candidate genes for milk traits, but also can serve as a routine method for GWAS in dairy cattle.}, } @article {pmid29751742, year = {2018}, author = {Liu, Y and Zhang, J and Xu, Q and Kang, X and Wang, K and Wu, K and Fang, M}, title = {Integrated miRNA-mRNA analysis reveals regulatory pathways underlying the curly fleece trait in Chinese tan sheep.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {360}, pmid = {29751742}, issn = {1471-2164}, support = {IRT1191//Program for Changjiang Scholars and Innovation Research Teams in China Agricultural University/ ; NXNYYZ20150101//breeding project for high-quality mutton sheep varieties (or lines) in Ningxia province/ ; }, mesh = {Animal Fur/*anatomy & histology ; Animals ; MicroRNAs/*genetics ; RNA, Messenger/genetics ; Sequence Analysis, RNA ; Sheep/*anatomy & histology/*genetics ; }, abstract = {BACKGROUND: Tan sheep is an indigenous Chinese breed well known for its beautiful curly fleece. One prominent breed characteristic of this sheep breed is that the degree of curliness differs markedly between lambs and adults, but the molecular mechanisms regulating the shift are still not well understood. In this study, we identified 49 differentially expressed (DE) microRNAs (miRNAs) between Tan sheep at the two stages through miRNA-seq, and combined the data with that in our earlier Suppression Subtractive Hybridization cDNA (SSH) library study to elucidate the mechanisms underlying curly fleece formation.

RESULTS: Thirty-six potential miRNA-mRNA target pairs were identified using computational methods, including 25 DE miRNAs and 10 DE genes involved in the MAPK signaling pathway, steroid biosynthesis and metabolic pathways. With the differential expressions between lambs and adults confirmed by qRT-PCR, some miRNAs were already annotated in the genome, but some were novel miRNAs. Inhibition of KRT83 expression by miR-432 was confirmed by both gene knockdown with siRNA and overexpression, which was consistent with the miRNAs and targets prediction results.

CONCLUSION: Our study represents the comprehensive analysis of mRNA and miRNA in Tan sheep and offers detailed insight into the development of curly fleece as well as the potential mechanisms controlling curly hair formation in humans.}, } @article {pmid29751739, year = {2018}, author = {Zheng, J and Li, H and Zhang, Q and Sun, L and Liu, X and Luo, C}, title = {Homologous recombination occurs frequently at innate GT microsatellites in normal somatic and germ cells in vivo.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {359}, pmid = {29751739}, issn = {1471-2164}, support = {2010CB126301//Development Program for Basic Research of China/ ; 30430370//National Natural Science Foundation of China (CN)/ ; }, mesh = {Animals ; DNA Breaks, Double-Stranded ; Germ Cells/cytology/*metabolism ; *Homologous Recombination ; Microsatellite Repeats/*genetics ; Mitosis/genetics ; Nucleotide Motifs ; }, abstract = {BACKGROUND: In somatic cells, homologous recombination (HR) is a rare event caused by eventual DNA double-strand breaks (DSBs). In contrast, germ cells show high frequency of HR caused by programmed DSBs. Microsatellites are prone to DSBs during genome replication and, thereby, capable of promoting HR. It remains unclear whether HR occurs frequently at microsatellites both in normal somatic cells and germ cells in a similar manner.

RESULTS: By examining the linkage pattern of multiple paternal and maternal markers flanking innate GT microsatellites, we measured HR at the GT microsatellites in various somatic cells and germ cells in a goldfish intraspecific heterozygote. During embryogenesis, the HR products accumulate gradually with the increase of the number of cell divisions. The frequency of HR at the GT microsatellites in advanced embryos, adult tissues and germ cells is surprisingly high. The type of exchanges between the homologous chromosomes is similar in normal advanced embryos and germ cells. Furthermore, a long GT microsatellite is more active than a short one in promoting HR in both somatic and germ cells.

CONCLUSIONS: HR occurs frequently at innate GT microsatellites in normal somatic cells and germ cells in a similar manner.}, } @article {pmid29751738, year = {2018}, author = {Kang, W and Zhu, X and Wang, Y and Chen, L and Duan, Y}, title = {Transcriptomic and metabolomic analyses reveal that bacteria promote plant defense during infection of soybean cyst nematode in soybean.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {86}, pmid = {29751738}, issn = {1471-2229}, support = {313300630//National Nature Science Fund Key Projects/ ; CARS-04-PS13//China Agriculture Research System/ ; }, mesh = {Animals ; Bacillus/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Genes, Plant/genetics/physiology ; Metabolomics ; Plant Diseases/immunology/*parasitology ; *Plant Immunity ; Plant Roots/metabolism/microbiology/parasitology ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Soybeans/genetics/metabolism/microbiology/*parasitology ; *Tylenchoidea ; }, abstract = {BACKGROUND: Soybean cyst nematode (SCN) is the most devastating pathogen of soybean. Our previous study showed that the plant growth-promoting rhizobacterium Bacillus simplex strain Sneb545 promotes soybean resistance to SCN. Here, we conducted a combined metabolomic and transcriptomic analysis to gain information regarding the biological mechanism of defence enhancement against SCN in Sneb545-treated soybean. To this end, we compared the transcriptome and metabolome of Sneb545-treated and non-treated soybeans under SCN infection.

RESULTS: Transcriptomic analysis showed that 6792 gene transcripts were common in Sneb545-treated and non-treated soybeans. However, Sneb545-treated soybeans showed a higher concentration of various nematicidal metabolites, including 4-vinylphenol, methionine, piperine, and palmitic acid, than non-treated soybeans under SCN infection.

CONCLUSIONS: Overall, our results validated and expanded the existing models regarding the co-regulation of gene expression and metabolites in plants, indicating the advantage of integrated system-oriented analysis.}, } @article {pmid29751737, year = {2018}, author = {Lee, T and Lee, S and Sim, WY and Jung, YM and Han, S and Won, JH and Min, H and Yoon, S}, title = {Correction to: HiComet: a high-throughput comet analysis tool for large-scale DNA damage assessment.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {170}, pmid = {29751737}, issn = {1471-2105}, abstract = {After publication of the original article [1], it has been found that the author affiliations have been accidentally left out in the PDF. The full affiliations can be found in this correction.}, } @article {pmid29751736, year = {2019}, author = {Munk, W and Wunsch, C}, title = {A Conversation with Walter Munk.}, journal = {Annual review of marine science}, volume = {11}, number = {}, pages = {15-25}, doi = {10.1146/annurev-marine-010318-095353}, pmid = {29751736}, issn = {1941-0611}, abstract = {In this interview, Carl Wunsch talks with Walter Munk about his career in oceanography; his relationships with scientists such as Harald Sverdrup, Roger Revelle, Walfrid Ekman, Carl Rossby, Carl Eckart, Henry Stommel, and G.I. Taylor; technological advances over the decades; and his thoughts on the future of the field.}, } @article {pmid29751732, year = {2018}, author = {Goonasekera, HW and Paththinige, CS and Dissanayake, VHW}, title = {Population Screening for Hemoglobinopathies.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {355-380}, doi = {10.1146/annurev-genom-091416-035451}, pmid = {29751732}, issn = {1545-293X}, abstract = {Hemoglobinopathies are the most common single-gene disorders in the world. Their prevalence is predicted to increase in the future, and low-income hemoglobinopathy-endemic regions need to manage most of the world's affected persons. International organizations, governments, and other stakeholders have initiated national or regional prevention programs in both endemic and nonendemic countries by performing population screening for α- and β-thalassemia, HbE disease, and sickle cell disease in neonates, adolescents, reproductive-age adults (preconceptionally or in the early antenatal period), and family members of diagnosed cases. The main aim of screening is to reduce the number of affected births and, in the case of sickle cell disease, reduce childhood morbidity and mortality. Screening strategies vary depending on the population group, but a few common screening test methods are universally used. We discuss the salient features of population-screening programs around the globe as well as current and proposed screening test methodologies.}, } @article {pmid29751087, year = {2018}, author = {Buján, N and Balboa, S and L Romalde, J and E Toranzo, A and Magariños, B}, title = {Population genetic and evolution analysis of controversial genus Edwardsiella by multilocus sequence typing.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {513-521}, doi = {10.1016/j.ympev.2018.05.006}, pmid = {29751087}, issn = {1095-9513}, mesh = {Edwardsiella/*classification/*genetics ; Evolution, Molecular ; Gene Flow ; *Multilocus Sequence Typing ; Mutation ; Phylogeny ; Recombination, Genetic ; }, abstract = {At present, the genus Edwardsiella compiles five species: E. tarda, E. hoshinae, E. ictaluri, E. piscicida and E. anguillarum. Some species of this genus such us E. ictaluri and E. piscicida are important pathogens of numerous fish species. With the description of the two latter species, the phylogeny of Edwardsiella became more complicated. With the aim to clarify the relationships among all species in the genus, a multilocus sequence typing (MLST) approach was developed and applied to characterize 56 isolates and 6 reference strains belonging to the five Edwardsiella species. Moreover, several analyses based on the MLST scheme were performed to investigate the evolution within the genus, as well as the influence of recombination and mutation in the speciation. Edwardsiella isolates presented a high genetic variability reflected in the fourteen sequence types (ST) represented by a single isolates out of eighteen total ST. Mutation events were considerably more frequent than recombination, although both approximately equal influenced the genetic diversification. However, the speciation among species occurred mostly by recombination. Edwardsiella genus displays a non-clonal population structure with some degree of geographical isolation followed by a population expansion of E. piscicida. A database from this study was created and hosted on pubmlst.org (http://pubmlst.org/edwardsiella/).}, } @article {pmid29751066, year = {2018}, author = {Gupta, S and Lemenze, A and Donnelly, RJ and Connell, ND and Kadouri, DE}, title = {Keeping it together: absence of genetic variation and DNA incorporation by the predatory bacteria Micavibrio aeruginosavorus and Bdellovibrio bacteriovorus during predation.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {237-243}, doi = {10.1016/j.resmic.2018.03.002}, pmid = {29751066}, issn = {1769-7123}, mesh = {Alphaproteobacteria/*genetics/isolation & purification ; Antibiosis/genetics ; Bdellovibrio bacteriovorus/*genetics/isolation & purification ; Biological Control Agents ; Coculture Techniques ; DNA, Bacterial/*genetics ; Gene Transfer, Horizontal ; Genetic Variation/*genetics ; Gram-Negative Bacterial Infections/therapy ; Humans ; Klebsiella pneumoniae/genetics ; }, abstract = {The use of predatory bacteria as a potential live therapeutic to control human infection is gaining increased attention. Earlier work with Micavibrio spp. and Bdellovibrio spp. has demonstrated the ability of these predators to control drug-resistant Gram-negative pathogens, Tier-1 select agents and biofilms. Additional studies also confirmed that introducing high doses of the predators into animals does not negatively impact animal well-being and might assist in reducing bacterial burden in vivo. The survival of predators requires extreme proximity to the prey cell, which might bring about horizontal transfer of genetic material, such as genes encoding for pathogenic genetic islands that would indirectly facilitate the spread of genetic material to other organisms. In this study, we examined the genetic makeup of several lab isolates of the predators Bdellovibriobacteriovorus and Micavibrioaeruginosavorus that were cultured repeatedly and stored over a course of 13 years. We also conducted controlled experiments in which the predators were sequentially co-cultured on Klebsiella pneumoniae followed by genetic analysis of the predator. In both cases, we saw little genetic variation and no evidence of horizontally transferred chromosomal DNA from the prey during predator-prey interaction. Culturing the predators repeatedly did not cause any change in predation efficacy.}, } @article {pmid29751065, year = {2018}, author = {Zhao, X and Liu, R and Tang, H and Osei-Adjei, G and Xu, S and Zhang, Y and Huang, X}, title = {A 3' UTR-derived non-coding RNA RibS increases expression of cfa and promotes biofilm formation of Salmonella enterica serovar Typhi.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {279-288}, doi = {10.1016/j.resmic.2018.04.007}, pmid = {29751065}, issn = {1769-7123}, mesh = {3' Untranslated Regions/*genetics ; Base Sequence ; Biofilms/*growth & development ; Gene Deletion ; Gene Knockout Techniques ; Methyltransferases/*genetics ; RNA, Untranslated/*genetics ; Riboflavin Synthase/*genetics ; Salmonella typhi/*genetics/metabolism/pathogenicity ; }, abstract = {Bacterial non-coding RNAs (ncRNAs) are widely studied and found to play important roles in regulating various cellular processes. Recently, many ncRNAs have been discovered to be transcribed or processed from 3' untranslated regions (3' UTRs). Here we reported a novel 3' UTR-derived ncRNA, RibS, which could influence biofilm formation of Salmonella enterica serovar Typhi (S. Typhi). RibS was confirmed to be a ∼700 nt processed product produced by RNase III-catalyzed cleavage from the 3' UTR of riboflavin synthase subunit alpha mRNA, RibE. Overexpression of RibS increased the expression of the cyclopropane fatty acid synthase gene, cfa, which was located at the antisense strand. Biofilm formation of S. Typhi was enhanced by overexpressing RibS both in the wild type strain and cfa deletion mutant. Deletion of cfa attenuated biofilm formation of S. Typhi, while complementation of cfa partly restored the phenotype. Moreover, overexpressing cfa enhanced the biofilm formation of S. Typhi. In summary, RibS has been identified as a novel ncRNA derived from the 3' UTR of RibE that promotes biofilm formation of S. Typhi, and it appears to do so, at least in part, by increasing the expression of cfa.}, } @article {pmid29751064, year = {2018}, author = {Eales, MG and Ferrari, E and Goddard, AD and Lancaster, L and Sanderson, P and Miller, C}, title = {Mechanistic and phenotypic studies of bicarinalin, BP100 and colistin action on Acinetobacter baumannii.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {296-302}, doi = {10.1016/j.resmic.2018.04.005}, pmid = {29751064}, issn = {1769-7123}, mesh = {Acinetobacter Infections/drug therapy/microbiology/prevention & control ; Acinetobacter baumannii/*drug effects ; Ant Venoms/*pharmacology ; Anti-Bacterial Agents/*pharmacology ; Antimicrobial Cationic Peptides/*pharmacology ; Biofilms/drug effects/*growth & development ; Colistin/*pharmacology ; Humans ; Microbial Sensitivity Tests ; Microscopy, Atomic Force ; Microscopy, Electron, Scanning ; Oligopeptides/*pharmacology ; }, abstract = {Acinetobacter baumannii has been identified by the WHO as a high priority pathogen. It can be resistant to multiple antibiotics and colistin sulphate is often used as a last-resort treatment. However, the potentially severe side-effects of colistin are well documented and this study compared the bactericidal and anti-biofilm activity of two synthetic nature-inspired antimicrobial peptides, bicarinalin and BP100, with colistin. The minimum bactericidal concentration (MBC) against planktonic A. baumannii was approximately 0.5 μg/ml for colistin sulphate and ∼4 μg/ml for bicarinalin and BP100. A. baumannii commonly occurs as a biofilm and biofilm removal assay results highlighted that both bicarinalin and BP100 had significantly greater potential than colistin. Atomic force microscopy (AFM) showed dramatic changes in A. baumannii cell size and surface conformity when treated with peptide concentrations at and above the MBC. Scanning electron microscopy (SEM) visualised the reduction of biofilm coverage and cell surface changes as peptide concentration increased. Liposome assays revealed that these peptides most likely act as pore-forming agents in the membrane. Bicarinalin and BP100 may be effective therapeutic alternatives to colistin against A. baumannii infections but further research is required to assess if they elicit cytotoxicity issues in patients.}, } @article {pmid29751063, year = {2018}, author = {Perrin, E and Bacci, G and Garrelly, L and Canganella, F and Bianconi, G and , and Fani, R and Mengoni, A}, title = {Furnishing spaceship environment: evaluation of bacterial biofilms on different materials used inside International Space Station.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {289-295}, doi = {10.1016/j.resmic.2018.04.001}, pmid = {29751063}, issn = {1769-7123}, mesh = {Actinomycetales/genetics/isolation & purification ; Bacillales/genetics/isolation & purification ; *Bacterial Load ; Biofilms/*growth & development ; Disinfectants/*pharmacology ; Enterobacteriaceae/genetics/isolation & purification ; Environmental Monitoring/*methods ; Equipment Contamination/*prevention & control ; Humans ; Hydrogen Peroxide/pharmacology ; Lactobacillales/genetics/isolation & purification ; Microbiota/*drug effects ; RNA, Ribosomal, 16S/genetics ; Silicon Dioxide/pharmacology ; Silver/pharmacology ; Spacecraft/*instrumentation ; Surface-Active Agents/pharmacology ; }, abstract = {Performed inside International Space Station (ISS) from 2011 to 2016, VIABLE (eValuatIon And monitoring of microBiofiLms insidE International Space Station) ISS was a long-lasting experiment aimed at evaluating the bacterial contamination on different surface space materials subjected to different pre-treatment, to provide useful information for future space missions. In this work, surfaces samples of the VIABLE ISS experiment were analyzed to determine both the total bacterial load (ATP-metry, qPCR) and the composition of the microbial communities (16S rRNA genes amplicon sequencing). Data obtained showed a low bacterial contamination of all the surfaces, with values in agreement with those allowed inside ISS, and with a taxonomic composition similar to those found in previous studies (Enterobacteriales, Bacillales, Lactobacillales and Actinomycetales). No pre-treatment or material effect were observed on both the bacterial load and the composition of the communities, but for both a slight effect of the position (expose/not expose to air) was observed. In conclusion, under the conditions used for VIABLE ISS, no material or pre-treatment seems to be better than others in terms of quantity and type of bacterial contamination.}, } @article {pmid29751062, year = {2018}, author = {Torres, D and Benavidez, I and Donadio, F and Mongiardini, E and Rosas, S and Spaepen, S and Vanderleyden, J and Pěnčík, A and Novák, O and Strnad, M and Frébortová, J and Cassán, F}, title = {New insights into auxin metabolism in Bradyrhizobium japonicum.}, journal = {Research in microbiology}, volume = {169}, number = {6}, pages = {313-323}, doi = {10.1016/j.resmic.2018.04.002}, pmid = {29751062}, issn = {1769-7123}, mesh = {Alanine/metabolism ; Bradyrhizobium/genetics/*metabolism ; Indoleacetic Acids/*metabolism ; Leucine/metabolism ; Phenylalanine/metabolism ; Plant Root Nodulation/physiology ; Polysaccharides, Bacterial/*biosynthesis ; Seeds/*microbiology ; Soybeans/*microbiology ; Symbiosis/physiology ; }, abstract = {Bacterial metabolism of phytohormones includes several processes such as biosynthesis, catabolism, conjugation, hydrolysis and homeostatic regulation. However, only biosynthesis and occasionally catabolism are studied in depth in microorganisms. In this work, we evaluated and reconsidered IAA metabolism in Bradyrhizobiumjaponicum E109, one of the most widely used strains for soybean inoculation around the world. The genomic analysis of the strain showed the presence of several genes responsible for IAA biosynthesis, mainly via indole-3-acetonitrile (IAN), indole-3-acetamide (IAM) and tryptamine (TAM) pathways. However; in vitro experiments showed that IAA is not accumulated in the culture medium in significant amounts. On the contrary, a strong degradation activity was observed after exogenous addition of 0.1 mM of IAA, IBA or NAA to the medium. B. japonicum E109 was not able to grow in culture medium containing IAA as a sole carbon source. In YEM medium, the bacteria degraded IAA and hydrolyzed amino acid auxin conjugates with alanine (IAAla), phenylalanine (IAPhe), and leucine (IAPhe), releasing IAA which was quickly degraded. Finally, the presence of exogenous IAA induced physiological changes in the bacteria such as increased biomass and exopolysaccharide production, as well as infection effectiveness and symbiotic behavior in soybean plants.}, } @article {pmid29751061, year = {2018}, author = {Jiang, X and Li, X and Sun, S and Jiang, L}, title = {The transcriptional regulator VarN contributes to Salmonella Typhimurium growth in macrophages and virulence in mice.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {214-221}, doi = {10.1016/j.resmic.2018.03.003}, pmid = {29751061}, issn = {1769-7123}, mesh = {Animals ; Bacterial Proteins/genetics ; Caco-2 Cells ; Cell Line ; Gene Expression Regulation, Bacterial/*genetics ; Humans ; Macrophages/*microbiology ; Membrane Proteins/genetics ; Mice ; RAW 264.7 Cells ; Salmonella Infections/pathology ; *Salmonella typhimurium/genetics/growth & development/pathogenicity ; Transcription Factors/*genetics ; Transcription, Genetic/*genetics ; Up-Regulation/genetics ; Virulence/genetics ; }, abstract = {Salmonella enterica serovar Typhimurium (S. Typhimurium) is a major intracellular pathogen of humans and animals and its survival and growth in macrophages is essential for its pathogenicity. The S. Typhimurium genome encodes more than 50 putative regulatory proteins, but their involvement in pathogenicity and their regulatory roles are largely unknown. In this study, we investigated the biological function of the S. Typhimurium STM4320 gene (named varN), which encodes a putative MerR family transcriptional regulator. We found that varN is upregulated 2.6- to 6.8-fold after S. Typhimurium enters murine macrophages. A varN mutant reduced S. Typhimurium growth in murine macrophages and attenuated virulence in mice. Moreover, we showed that deletion of varN decreased the transcription of Salmonella pathogenicity island-2 (SPI-2) genes, which are required for S. Typhimurium growth in macrophages, indicative of the positive regulation of SPI-2 by VarN. We confirmed that the virulence defects of the varN mutant are entirely dependent on its regulation of SPI-2. Thus, our results revealed that VarN is a novel activator of the expression of SPI-2 genes and contributes to S. Typhimurium growth in macrophages and virulence in mice. Our findings provide a significant example of how a putative regulatory protein facilitates S. Typhimurium pathogenicity.}, } @article {pmid29751060, year = {2018}, author = {Kim, J and Ha, S and Park, W}, title = {Expression and deletion analyses of cspE encoding cold-shock protein E in Acinetobacter oleivorans DR1.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {244-253}, doi = {10.1016/j.resmic.2018.04.011}, pmid = {29751060}, issn = {1769-7123}, mesh = {5' Untranslated Regions/genetics ; Acinetobacter/*genetics/*growth & development/metabolism ; Biofilms/growth & development ; Cold-Shock Response/*genetics ; Gene Expression Regulation, Bacterial/*genetics ; Heat-Shock Proteins/biosynthesis/*genetics ; Promoter Regions, Genetic/genetics ; Soil Microbiology ; Transcription Initiation Site ; Transcription, Genetic/genetics ; }, abstract = {Six genes encoding cold-shock-like proteins, including cspE, are contained within the genome of Acinetobacter oleivorans DR1. All six genes are similar in size as well as amino acid identity, but appear to be differentially regulated under stressful conditions. Four of these genes (cspA, cspB, cspC and cspE) were functionally important during cold shock because of their gradual upregulation during a temperature decrease under our assay conditions. cspE also showed higher expression during alkane degradation and antibiotic exposure. The transcriptional start site of the cspE gene was determined using 5' rapid amplification of complementary DNA ends. Next, promoter analysis using numerous constructed gfp reporter strains containing deleted fragments of cspE upstream regions identified possible 5' untranslated region (UTR) cis-DNA elements that could be involved in modulating cspE expression. Deletion of cspE led to a growth defect and enhanced biofilm formation, but only at a low temperature. Collectively, our findings show the importance of CspE during cold shock, dynamic regulation of cspE expression under various stressful conditions and a possible 5'-UTR cis-DNA element for regulation of cspE expression. These data provide molecular insight into cspE gene expression during cold-shock adaptation in soil bacteria.}, } @article {pmid29750564, year = {2018}, author = {Mattey, SN and Richardson, J and Ratz, T and Smiseth, PT}, title = {Effects of Offspring and Parental Inbreeding on Parent-Offspring Communication.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {716-725}, doi = {10.1086/697236}, pmid = {29750564}, issn = {1537-5323}, abstract = {There is mounting evidence that inbreeding can have complex effects on social interactions among inbred and outbred individuals. Here, we investigate effects of offspring and maternal inbreeding on parent-offspring communication in the burying beetle Nicrophorus vespilloides. We find effects of the interaction between offspring and maternal inbreeding on maternal behavior. Outbred females provided more direct care toward inbred larvae, while inbred females provided similar levels of direct care toward inbred and outbred larvae. Furthermore, we find direct and indirect effects of offspring inbreeding on offspring begging and maternal behavior, respectively. Inbred larvae spent less time begging than outbred larvae, and (outbred) females provided more direct care and less indirect care toward inbred larvae. Finally, we find effects of the interaction between offspring and maternal inbreeding on larval body mass. Inbred and outbred offspring grew to a similar size when the female was outbred, while inbred offspring were of a smaller size when the female was inbred. Our results suggest that outbred females provided more care toward inbred offspring to compensate for their poor genetic quality. Our study advances our understanding of inbreeding by showing that inbreeding can have direct effects on the behavior of inbred individuals and indirect effects on the behavior of outbred individuals and that indirect effects on outbred individuals may in turn influence the fitness of inbred individuals.}, } @article {pmid29750563, year = {2018}, author = {Lemanski, NJ and Fefferman, NH}, title = {How Life History Shapes Optimal Patterns of Senescence: Implications from Individuals to Societies.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {756-766}, doi = {10.1086/697225}, pmid = {29750563}, issn = {1537-5323}, abstract = {One evolutionary view of aging, the disposable soma theory, suggests that an organism's rate of senescence depends on the amount of energy invested in somatic maintenance. Since organisms have limited energy to allocate among growth, maintenance, and reproduction, the optimal amount of energy to invest in maintenance is influenced by the probability of death from extrinsic causes and the effect of somatic investment on survival. In eusocial animals, the disposable soma theory can be used to explain colonies' energy investment in the longevity of workers, who act as the somatic elements of a superorganism. There have been few theoretical considerations of how changes in the costliness of worker maintenance or in the effect of individual life span on group fitness influence a colony's investment in worker longevity. We develop a decision theory model to evaluate how changing the marginal costs and benefits of longevity and extrinsic mortality influence optimal worker life span in a social insect colony. Our model predicts that higher extrinsic mortality favors shorter life span. However, increased life span is favored when marginal benefits are an increasing function of longevity. In honeybees, this explains how greater somatic investment is sometimes favored despite high mortality. Our approach expands the disposable soma theory to make quantitative predictions about the selective pressures shaping senescence in social systems.}, } @article {pmid29750562, year = {2018}, author = {Matsuura, K and Mizumoto, N and Kobayashi, K and Nozaki, T and Fujita, T and Yashiro, T and Fuchikawa, T and Mitaka, Y and Vargo, EL}, title = {A Genomic Imprinting Model of Termite Caste Determination: Not Genetic but Epigenetic Inheritance Influences Offspring Caste Fate.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {677-690}, doi = {10.1086/697238}, pmid = {29750562}, issn = {1537-5323}, abstract = {Eusocial insects exhibit the most striking example of phenotypic plasticity. There has been a long controversy over the factors determining caste development of individuals in social insects. Here we demonstrate that parental phenotypes influence the social status of offspring not through genetic inheritance but through genomic imprinting in termites. Our extensive field survey and genetic analysis of the termite Reticulitermes speratus show that its breeding system is inconsistent with a genetic caste determination model. We therefore developed a genomic imprinting model, in which queen- and king-specific epigenetic marks antagonistically influence sexual development of offspring. The model accounts for all known empirical data on caste differentiation of R. speratus and other related species. By conducting colony-founding experiments and additively incorporating relevant socio-environmental factors into our genomic imprinting model, we show the relative importance of genomic imprinting and environmental factors in caste determination. The idea of epigenetic inheritance of sexual phenotypes solves the puzzle of why parthenogenetically produced daughters carrying only maternal chromosomes exclusively develop into queens and why parental phenotypes (nymph- or worker-derived reproductives) strongly influence caste differentiation of offspring. According to our model, the worker caste is seen as a "neuter" caste whose sexual development is suppressed due to counterbalanced maternal and paternal imprinting and opens new avenues for understanding the evolution of caste systems in social insects.}, } @article {pmid29750561, year = {2018}, author = {Conith, AJ and Meagher, MA and Dumont, ER}, title = {The Influence of Climatic Variability on Morphological Integration, Evolutionary Rates, and Disparity in the Carnivora.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {704-715}, doi = {10.1086/697376}, pmid = {29750561}, issn = {1537-5323}, abstract = {Biodiversity is unevenly distributed in space and time. One possible explanation for this is the influence of climate on the ecology, evolution, and morphology of taxa. Here we investigated the link between climatic variability and phenotypic integration, rates of morphological evolution, and disparity (morphological diversity) in three carnivoran clades (Canidae, Felidae, and Mustelidae). We gathered landmark data from the lower jaw and extracted current temperature and precipitation data from range maps. We found a significant negative relationship between climatic variability and integration for canids and felids. Among canids, variability in temperature was the key climatic variable, while in felids it was a combination of variability in temperature and precipitation. In both cases, relatively variable climates were associated with low phenotypic integration. We also found evidence for a negative association between climatic variability and both disparity and rates of morphological evolution in canids and mustelids. Selection can drive the evolution of jaw shape along lines of least resistance defined by patterns of integration, and this study suggests that climate may be a predictor of phenotypic integration. As a result, taxa in more variable regions (e.g., temperate, montane) may be more evolvable and more able to respond to fluctuating environmental conditions over a period of generations.}, } @article {pmid29750560, year = {2018}, author = {Wieczynski, DJ and Turner, PE and Vasseur, DA}, title = {Temporally Autocorrelated Environmental Fluctuations Inhibit the Evolution of Stress Tolerance.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {E195-E207}, doi = {10.1086/697200}, pmid = {29750560}, issn = {1537-5323}, abstract = {As global environmental conditions continue to change at an unprecedented rate, many species will experience increases in natural and anthropogenic stress. Generally speaking, selection is expected to favor adaptations that reduce the negative impact of environmental stress (i.e., stress tolerance). However, natural environmental variables typically fluctuate, exhibiting various degrees of temporal autocorrelation, known as environmental colors, which may complicate evolutionary responses to stress. Here we combine experiments and theory to show that temporal environmental autocorrelation can determine long-term evolutionary responses to stress without affecting the total amount of stress experienced over time. Experimental evolution of RNA virus lineages in differing environmental autocorrelation treatments agreed closely with predictions from our theoretical models that stress tolerance is favored in less autocorrelated (whiter) environments but disfavored in more autocorrelated (redder) environments. This is explained by an interaction between environmental autocorrelation and a phenotypic trade-off between stress tolerance and reproductive ability. The degree to which environmental autocorrelation influences evolutionary trajectories depends on the shape of this trade-off as well as the relative level of tolerance exhibited by novel mutants. These results suggest that long-term evolutionary dynamics depend not only on the overall strength of selection but also on the way that selection is distributed over time.}, } @article {pmid29750559, year = {2018}, author = {Grunst, AS and Grunst, ML and Formica, VA and Korody, ML and Betuel, AM and Barcelo-Serra, M and Ford, S and Gonser, RA and Tuttle, EM}, title = {Morph-Specific Patterns of Reproductive Senescence: Connections to Discrete Reproductive Strategies.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {744-755}, doi = {10.1086/697377}, pmid = {29750559}, issn = {1537-5323}, abstract = {How reproductive strategies contribute to patterns of senescence in natural populations remains contentious. We studied reproductive senescence in the dimorphic white-throated sparrow, an excellent species for exploring this issue. Within both sexes the morphs use distinct reproductive strategies, and disassortative pairing by morph results in pair types with distinct parental systems. White morph birds are more colorful and aggressive than tan counterparts, and white males compete for extrapair matings, whereas tan males are more parental. Tan males and white females share parental care equally, whereas white males provide little parental support to tan females. We found morph-specific patterns of reproductive senescence in both sexes. White males exhibited greater reproductive senescence than tan males. This result likely reflects the difficulty of sustaining a highly competitive reproductive strategy as aging progresses rather than high physiological costs of competitiveness, since white males were also long-lived. Moreover, morph was not consistently related to reproductive senescence across the sexes, arguing against especially high costs of the traits associated with white morph identity. Rather, tan females exhibited earlier reproductive senescence than white females and were short-lived, perhaps reflecting the challenges of unsupported motherhood. Results underscore the importance of social dynamics in determining patterns of reproductive senescence.}, } @article {pmid29750558, year = {2018}, author = {Poe, S and de Oca, AN and Torres-Carvajal, O and de Queiroz, K and Velasco, JA and Truett, B and Gray, LN and Ryan, MJ and Köhler, G and Ayala-Varela, F and Latella, I}, title = {Comparative Evolution of an Archetypal Adaptive Radiation: Innovation and Opportunity in Anolis Lizards.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {E185-E194}, doi = {10.1086/697223}, pmid = {29750558}, issn = {1537-5323}, abstract = {Adaptive radiation is a widely recognized pattern of evolution wherein substantial phenotypic change accompanies rapid speciation. Adaptive radiation may be triggered by environmental opportunities resulting from dispersal to new areas or via the evolution of traits, called key innovations, that allow for invasion of new niches. Species sampling is a known source of bias in many comparative analyses, yet classic adaptive radiations have not been studied comparatively with comprehensively sampled phylogenies. In this study, we use unprecedented comprehensive phylogenetic sampling of Anolis lizard species to examine comparative evolution in this well-studied adaptive radiation. We compare adaptive radiation models within Anolis and in the Anolis clade and a potential sister lineage, the Corytophanidae. We find evidence for island (i.e., opportunity) effects and no evidence for trait (i.e., key innovation) effects causing accelerated body size evolution within Anolis. However, island effects are scale dependent: when Anolis and Corytophanidae are analyzed together, no island effect is evident. We find no evidence for an island effect on speciation rate and tenuous evidence for greater speciation rate due to trait effects. These results suggest the need for precision in treatments of classic adaptive radiations such as Anolis and further refinement of the concept of adaptive radiation.}, } @article {pmid29750557, year = {2018}, author = {Svensson, EI and Gómez-Llano, MA and Torres, AR and Bensch, HM}, title = {Frequency Dependence and Ecological Drift Shape Coexistence of Species with Similar Niches.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {691-703}, doi = {10.1086/697201}, pmid = {29750557}, issn = {1537-5323}, abstract = {The coexistence of ecologically similar species might be counteracted by ecological drift and demographic stochasticity, both of which erode local diversity. With niche differentiation, species can be maintained through performance trade-offs between environments, but trade-offs are difficult to invoke for species with similar ecological niches. Such similar species might then go locally extinct due to stochastic ecological drift, but there is little empirical evidence for such processes. Previous studies have relied on biogeographical surveys and inferred process from pattern, while experimental field investigations of ecological drift are rare. Mechanisms preserving local species diversity, such as frequency dependence (e.g., rare-species advantages), can oppose local ecological drift, but the combined effects of ecological drift and such counteracting forces have seldom been investigated. Here, we investigate mechanisms between coexistence of ecologically similar but strongly sexually differentiated damselfly species (Calopteryx virgo and Calopteryx splendens). Combining field surveys, behavioral observations, experimental manipulations of species frequencies and densities, and simulation modeling, we demonstrate that species coexistence is shaped by the opposing forces of ecological drift and negative frequency dependence (rare-species advantage), generated by interference competition. Stochastic and deterministic processes therefore jointly shape coexistence. The role of negative frequency dependence in delaying the loss of ecologically similar species, such as those formed by sexual selection, should therefore be considered in community assembly, macroecology, macroevolution, and biogeography.}, } @article {pmid29750556, year = {2018}, author = {Bauer, CM and Graham, JL and Abolins-Abols, M and Heidinger, BJ and Ketterson, ED and Greives, TJ}, title = {Chronological and Biological Age Predict Seasonal Reproductive Timing: An Investigation of Clutch Initiation and Telomeres in Birds of Known Age.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {777-782}, doi = {10.1086/697224}, pmid = {29750556}, issn = {1537-5323}, abstract = {Female vertebrates that breed earlier in the season generally have greater reproductive success. However, evidence suggests that breeding early may be costly, thus leading to the prediction that females with fewer future reproductive events will breed earlier in the season. While chronological age is a good indicator of remaining life span, telomere lengths may also be good biomarkers of longevity as they potentially reflect lifetime wear and tear (i.e., biological age). We examined whether variation in the timing of the first seasonal clutch was related to age and telomere length in female dark-eyed juncos (Junco hyemalis), predicting that older females and those with shorter telomeres would breed earlier. Both predictions held true and were independent of each other, as telomere length did not significantly vary with age. These results suggest that females may adjust their reproductive effort based on both chronological and biological age.}, } @article {pmid29750555, year = {2018}, author = {Fargallo, JA and Martínez, F and Wakamatsu, K and Serrano, D and Blanco, G}, title = {Sex-Dependent Expression and Fitness Consequences of Sunlight-Derived Color Phenotypes.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {726-743}, doi = {10.1086/697218}, pmid = {29750555}, issn = {1537-5323}, abstract = {To understand whether early phenotypes are adaptive, knowledge of the environmental factors involved in their variation and the derived benefits from their expression is needed. Temperature and sunlight are considered two major selective forces influencing phenotypic coloration of birds at a global scale. However, within-population color adaptations in response to sunlight temperature variation have been scarcely investigated, and their acclimatization capacity is currently unknown. In addition, the sexes differ in their sensitivity to environmental factors during growth. This study evaluates how melanin plumage coloration varies in relation to sex and sunlight exposure in developing griffon vultures Gyps fulvus and how this correlates with survival. The results show that individuals grown in nests more exposed to sunlight developed paler plumages, as predicted by the thermal melanism hypothesis. In addition, paler males-but not females-have lower survival probability. Finally, a significant sexual dichromatism in fledgling plumage was observed, with females being paler than males. These results reveal within-population color variation related to sunlight temperature conditions, probably as a capacity for local acclimatization through color plasticity, and also provide evidence of sex differences in fitness optima for this trait under ecological pressures.}, } @article {pmid29750554, year = {2018}, author = {Switzer, CM and Combes, SA and Hopkins, R}, title = {Dispensing Pollen via Catapult: Explosive Pollen Release in Mountain Laurel (Kalmia latifolia).}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {767-776}, doi = {10.1086/697220}, pmid = {29750554}, issn = {1537-5323}, abstract = {The astonishing amount of floral diversity has inspired countless assumptions about the function of diverse forms and their adaptive significance, yet many of these hypothesized functions are untested. We investigated an often-repeated adaptive hypothesis about how an extreme floral form functions. In this study, we conducted four investigations to understand the adaptive function of explosive pollination in Kalmia latifolia, the mountain laurel. We first performed a kinematic analysis of anther movement. Second, we constructed a heat map of pollen trajectories in three-dimensional space. Third, we conducted field observations of pollinators and their behaviors while visiting K. latifolia. Finally, we conducted a pollination experiment to investigate the importance of pollinators for fertilization success. Our results suggest that insect visitation dramatically improves fertilization success and that bees are the primary pollinators that trigger explosive pollen release.}, } @article {pmid29750553, year = {2018}, author = {Wittmann, MJ and Fukami, T}, title = {Eco-Evolutionary Buffering: Rapid Evolution Facilitates Regional Species Coexistence despite Local Priority Effects.}, journal = {The American naturalist}, volume = {191}, number = {6}, pages = {E171-E184}, doi = {10.1086/697187}, pmid = {29750553}, issn = {1537-5323}, abstract = {Inhibitory priority effects, in which early-arriving species exclude competing species from local communities, are thought to enhance regional species diversity via community divergence. Theory suggests, however, that these same priority effects make it difficult for species to coexist in the region unless individuals are continuously supplied from an external species pool, often an unrealistic assumption. Here we develop an eco-evolutionary hypothesis to solve this conundrum. We build a metacommunity model in which local priority effects occur between two species via interspecific interference. Within each species there are two genotypes: one is more resistant to interspecific interference than the other but pays a fitness cost for its resistance. Because of this trade-off, species evolve to become less resistant as they become regionally more common. Rare species can then invade some local patches and consequently recover in regional frequency. This "eco-evolutionary buffering" enables the regional coexistence of species despite local priority effects, even in the absence of immigration from an external species pool. Our model predicts that eco-evolutionary buffering is particularly effective when local communities are small and connected by infrequent dispersal.}, } @article {pmid29750400, year = {2018}, author = {Timmis, K}, title = {Environmental microbiology - the next 20 years: bioconnectivity and meta'omics 2.0.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14236}, pmid = {29750400}, issn = {1462-2920}, } @article {pmid29750394, year = {2018}, author = {Kolter, R and Chimileski, S}, title = {The end of microbiology.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14240}, pmid = {29750394}, issn = {1462-2920}, } @article {pmid29750393, year = {2018}, author = {Lobov, AA and Maltseva, AL and Starunov, VV and Babkina, IY and Ivanov, VA and Mikhailova, NA and Granovitch, AI}, title = {LOSP: A putative marker of parasperm lineage in male reproductive system of the prosobranch mollusk Littorina obtusata.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {4}, pages = {193-201}, doi = {10.1002/jez.b.22803}, pmid = {29750393}, issn = {1552-5015}, abstract = {Reproductive isolation is the key attribute of biological species and establishment of the reproductive barriers is an essential event for speciation. Among the mechanisms of reproductive isolation, gamete incompatibility due to the variability of gamete interaction proteins may drive fast divergence even in sympatry. However, the number of available models to study this phenomenon is limited. In case of internally fertilized invertebrates, models to study gamete incompatibility and sperm competition mechanisms are restricted to a single taxon: insects. Here, we propose a group of closely related Littorina species as a new model for such studies. Particularly since periwinkles are already thoroughly studied in terms of morphology, physiology, ecology, phylogeny, and ecological speciation. Earlier, we have identified the first species-specific Littorina sperm protein (LOSP) with no known conservative domains or homologies. LOSP is relatively abundant component of sperm extracts and might be involved in gamete incompatibility. Here, we characterize its definitive localization and mRNA expression pattern in the male reproductive system by immunocytochemistry and RNA in situ hybridization. We demonstrate that LOSP distribution is limited to the parasperm cells. Losp gene expression occurs only at the early stages of parasperm development. The protein is stored within granules of mature parasperm and, most likely, is released after ejaculation inside female reproductive system. Thus, LOSP is the only described molluscan paraspermal protein to date, and there is a possibility for LOSP to be involved in gamete incompatibility since heterospermy is a common phenomenon among Littorina.}, } @article {pmid29750330, year = {2018}, author = {Midhun, SJ and Neethu, S and Vysakh, A and Radhakrishnan, EK and Jyothis, M}, title = {Antagonism Against Fish Pathogens by Cellular Components/Preparations of Bacillus coagulans (MTCC-9872) and It's In Vitro Probiotic Characterisation.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29750330}, issn = {1432-0991}, abstract = {Bacterial fish pathogens are pervasive in aquaculture. Control of bacterial fish pathogen is a difficult task among aquaculture practitioners. A large number of antibiotics are used for the control of prevalent bacterial pathogens in aquaculture. This may lead to drug resistance among pathogens and further treatment will be ineffective. Here, we can use probiotic bacteria as a biocontrol agent in fish disease and it is a novel field. In this study, antimicrobial potential of the bacterium Bacillus coagulans (MTCC-9872) has been evaluated through in vitro antagonistic activity of cellular preparations/components against potent pathogens. The cellular preparations/components such as Ethyl acetate extract, whole-cell product, heat-killed whole-cell product, and filtered broth were exhibited bactericidal activity against the tested pathogens. Bactericidal activity varied among different cellular preparation/components. The tested bacterium effectively produced biofilm as significant as tested positive control in a microtitre plate and effectively adhered on to the glass slide. In addition, the bacterium was capable of producing extracellular enzymes necessary for the digestion of food materials and was capable to grow in fish mucus from Oreochromis niloticus. The bacterium tolerated bile juice secreted by the host. Moreover, intraperitoneal injection of the bacterium did not induce any pathological signs, symptoms or mortalities in Oreochromis niloticus and revealed the safety of this bacterium in the fish.}, } @article {pmid29750329, year = {2018}, author = {Wang, J and Liang, J and Gao, S}, title = {Biodegradation of Lignin Monomers Vanillic, p-Coumaric, and Syringic Acid by the Bacterial Strain, Sphingobacterium sp. HY-H.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, pmid = {29750329}, issn = {1432-0991}, abstract = {Many bacterial strains have been demonstrated to biodegrade lignin for contaminant removal or resource regeneration. The goal of this study was to investigate the biodegradation amount and associated pathways of three lignin monomers, vanillic, p-coumaric, and syringic acid by strain Sphingobacterium sp. HY-H. Vanillic, p-coumaric, and syringic acid degradation with strain HY-H was estimated as 88.71, 76.67, and 72.78%, respectively, after 96 h. Correspondingly, the same three monomers were associated with a COD removal efficiency of 87.30, 55.17, and 67.23%, and a TOC removal efficiency of 82.14, 61.03, and 43.86%. The results of GC-MS, HPLC, FTIR, and enzyme activities show that guaiacol and o-dihydroxybenzene are key intermediate metabolites of the vanillic acid and syringic acid degradation. p-Hydroxybenzoic acid is an important intermediate metabolite for p-coumaric and syringic acid degradation. LiP and MnP play an important role in the degradation of lignin monomers and their intermediate metabolites. One possible pathway is that strain HY-H degrades lignin monomers into guaiacol (through decarboxylic and demethoxy reaction) or p-hydroxybenzoic acid (through side-chain oxidation); then guaiacol demethylates to o-dihydroxybenzene. The p-hydroxybenzoic acid and o-dihydroxybenzene are futher through ring cleavage reaction to form small molecule acids (butyric, valproic, oxalic acid, and propionic acid) and alcohols (ethanol and ethanediol), then these acids and alcohols are finally decomposed into CO2 and H2O through the tricarboxylic acid cycle. If properly optimized and controlled, the strain HY-H may play a role in breaking down lignin-related compounds for biofuel and chemical production.}, } @article {pmid29749925, year = {2018}, author = {Lu, H and Xing, P and Phurbu, D and Tang, Q and Wu, Q}, title = {Pelagibacterium montanilacus sp. nov., an alkaliphilic bacterium isolated from Lake Cuochuolong on the Tibetan Plateau.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2220-2225}, doi = {10.1099/ijsem.0.002812}, pmid = {29749925}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Hyphomicrobiaceae/*classification/genetics/isolation & purification ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tibet ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain negative, alkaliphilic and halotolerant bacterium, designated CCL18T, was isolated from Lake Cuochuolong on the Tibetan Plateau. The strain was aerobic, short rod-shaped, catalase- and oxidase-positive, and motile by means of several polar flagella. Phylogenetic analysis based on 16S rRNA gene sequencing indicated that strain CCL18T belongs to the genus Pelagibacterium, with its two closest neighbours being Pelagibacterium halotolerans B2T (96.6 %, 16S rRNA gene sequence similarity) and Pelagibacterium luteolum 1_C16_27T (96.1 %). The predominant respiratory quinone of strain CCL18T was Q-10, with Q-9 as a minor component. The major fatty acids were C18 : 1ω6c/C18 : 1ω7c (60.4 %), C19 : 0cyclo ω8c (8.1 %) and C18 : 0 (6.8 %). The polar lipids included phosphatidylglycerol, diphosphatidylglycerol, seven kinds of unidentified lipids and three kinds of glycolipids. The DNA G+C content was 60.1 mol%. DNA-DNA hybridization showed 35.2 % relatedness between strain CCL18T and P. halotolerans B2T and 24.6 % relatedness to P. luteolum 1_C16_27T. Based on phylogenetic analysis, DNA-DNA hybridization and a range of physiological and biochemical characteristics, strain CCL18T was clearly distinguishable from the other strains of the genus Pelagibacterium. It was evident that strain CCL18T could be classified as a novel species of the genus Pelagibacterium, for which the name Pelagibacterium montanilacus sp. nov. is proposed. The type strain is CCL18T (=CGMCC 1.16231T=KCTC 62030T).}, } @article {pmid29749924, year = {2018}, author = {Jin, D and Kong, X and Wang, J and Sun, J and Yu, X and Zhuang, X and Deng, Y and Bai, Z}, title = {Chitinophaga caeni sp. nov., isolated from activated sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2209-2213}, doi = {10.1099/ijsem.0.002811}, pmid = {29749924}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; Beijing ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-negative, non-motile, non-spore-forming, rod-shaped, strictly aerobic bacterium, designated strain 13T, was isolated from an activated sludge wastewater treatment plant in Beijing, China. 16S rRNA gene sequence analysis placed this organism within the genus Chitinophaga of the class Bacteroidetes, with Chitinophaga skermanii CC-SG1B (92.4 % gene sequence similarity) and Chitinophaga rupis CS5-B1 (91.2 %) as its closest relatives. This isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and the whole-cell hydrolysate was ribose. Phosphatidylethanolamine was the predominant polar lipid. The major cellular fatty acids were iso-C15 : 0, C16 : 1ω5c and iso-C17 : 0 3-OH. Menaquinone-7 was the only isoprenoid quinone present. The complete genome of the novel strain was sequenced; the size of the genome was 5.28 Mb and the genomic DNA G+C content was 42.5 mol%. The phenotypic, chemotaxonomic and phylogenetic data showed that strain 13T represents a novel species of the genus Chitinophaga, for which the name Chitinophaga caeni sp. nov. is proposed. The type strain is 13T (=CICC 24262T=KCTC 62265T).}, } @article {pmid29749923, year = {2018}, author = {Saha, T and Chakraborty, B and Das, S and Thakur, N and Chakraborty, R}, title = {Chryseomicrobium excrementi sp. nov., a Gram-stain-positive rod-shaped bacterium isolated from an earthworm (Eisenia fetida) cast.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2165-2171}, doi = {10.1099/ijsem.0.002791}, pmid = {29749923}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Genome, Bacterial ; India ; Nucleic Acid Hybridization ; Oligochaeta/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Planococcaceae/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, rod-shaped, slightly halotolerant, nitrate-reducing bacterial strain, designated ET03T, was isolated from the cast of an earthworm (Eisenia fetida) reared at the Centre of Floriculture and Agribusiness Management, University of North Bengal at Siliguri, West Bengal, India. On the basis of 16S rRNA gene sequence phylogeny, the closest relative of strain ET03T was Chryseomicrobium palamuruense PU1T (99.1 % similarity). The DNA G+C content of strain ET03T was 42.9 mol%. Strain ET03T contained menaquinone-8 as the most predominant menaquinone and phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and phosphatidylglycerol as the main polar lipids. The diagnostic diamino acid was meso-diaminopimelic acid. Major cellular fatty acids were iso-C15 : 0, C16 : 1ω7c alcohol and iso-C16 : 0. Other biochemical and physiological analyses supported genotypic and phenotypic differentiation of the strain ET03T from its nearest taxonomic neighbours: Chryseomicrobium palamuruense,Chryseomicrobium amylolyticum, Chryseomicrobium imtechense, Chryseomicrobium aureum and Chryseomicrobium deserti. The draft genome of strain ET03T consisted of 2.64 Mb distributed in 14 scaffolds (N50 894072). A total of 2728 genes were predicted and, of those, 2664 were protein-coding genes including genes involved in the degradation of polychlorinated biphenyl and several aromatic compounds. The isolate, therefore, represents a novel species, for which the name Chryseomicrobium excrementi sp. nov. is proposed. The type strain is ET03T (=KCTC 33943T=LMG 30119T=JCM 32415T).}, } @article {pmid29749714, year = {2018}, author = {Bachy, C and Charlesworth, CJ and Chan, AM and Finke, JF and Wong, CH and Wei, CL and Sudek, S and Coleman, ML and Suttle, CA and Worden, AZ}, title = {Transcriptional responses of the marine green alga Micromonas pusilla and an infecting prasinovirus under different phosphate conditions.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2898-2912}, doi = {10.1111/1462-2920.14273}, pmid = {29749714}, issn = {1462-2920}, abstract = {Prasinophytes are widespread marine algae for which responses to nutrient limitation and viral infection are not well understood. We studied the picoprasinophyte, Micromonas pusilla, grown under phosphate-replete (0.65 ± 0.07 d-1) and 10-fold lower (low)-phosphate (0.11 ± 0.04 d-1) conditions, and infected by the phycodnavirus MpV-SP1. Expression of 17% of Micromonas genes in uninfected cells differed by >1.5-fold (q < 0.01) between nutrient conditions, with genes for P-metabolism and the uniquely-enriched Sel1-like repeat (SLR) family having higher relative transcript abundances, while phospholipid-synthesis genes were lower in low-P than P-replete. Approximately 70% (P-replete) and 30% (low-P) of cells were lysed 24 h post-infection, and expression of ≤5.8% of host genes changed relative to uninfected treatments. Host genes for CAZymes and glycolysis were activated by infection, supporting importance in viral production, which was significantly lower in slower growing (low-P) hosts. All MpV-SP1 genes were expressed, and our analyses suggest responses to differing host-phosphate backgrounds involve few viral genes, while the temporal program of infection involves many more, and is largely independent of host-phosphate background. Our study (i) identifies genes previously unassociated with nutrient acclimation or viral infection, (ii) provides insights into the temporal program of prasinovirus gene expression by hosts and (iii) establishes cell biological aspects of an ecologically important host-prasinovirus system that differ from other marine algal-virus systems.}, } @article {pmid29749705, year = {2018}, author = {Gargari, G and Taverniti, V and Gardana, C and Cremon, C and Canducci, F and Pagano, I and Barbaro, MR and Bellacosa, L and Castellazzi, AM and Valsecchi, C and Tagliacarne, SC and Bellini, M and Bertani, L and Gambaccini, D and Marchi, S and Cicala, M and Germanà, B and Dal Pont, E and Vecchi, M and Ogliari, C and Fiore, W and Stanghellini, V and Barbara, G and Guglielmetti, S}, title = {Fecal Clostridiales distribution and short-chain fatty acids reflect bowel habits in irritable bowel syndrome.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3201-3213}, doi = {10.1111/1462-2920.14271}, pmid = {29749705}, issn = {1462-2920}, abstract = {Irritable bowel syndrome (IBS), a common functional gastrointestinal disorder, is classified according to bowel habits as IBS with constipation (IBS-C), with diarrhea (IBS-D), with alternating constipation and diarrhea (IBS-M), and unsubtyped (IBS-U). The mechanisms leading to the different IBS forms are mostly unknown. This study aims to evaluate whether specific fecal bacterial taxa and/or short-chain fatty acids (SCFAs) can be used to distinguish IBS subtypes and are relevant for explaining the clinical differences between IBS subcategories. We characterized five fecal samples collected at 4-weeks intervals from 40 IBS patients by 16S rRNA gene profiling and SCFA quantification. Finally, we investigated the potential correlations in IBS subtypes between the fecal microbial signatures and host physiological and clinical parameters. We found significant differences in the distribution of Clostridiales OTUs among IBS subtypes and reduced levels of SCFAs in IBS-C compared to IBS-U and IBS-D patients. Correlation analyses showed that the diverse representation of Clostridiales OTUs between IBS subtypes was associated with altered levels of SCFAs; furthermore, the same OTUs and SCFAs were associated with the fecal cytokine levels and stool consistency. Our results suggest that intestinal Clostridiales and SCFAs might serve as potential mechanistic biomarkers of IBS subtypes and represent therapeutic targets.}, } @article {pmid29749696, year = {2018}, author = {Amenabar, MJ and Colman, DR and Poudel, S and Roden, EE and Boyd, ES}, title = {Electron acceptor availability alters carbon and energy metabolism in a thermoacidophile.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2523-2537}, doi = {10.1111/1462-2920.14270}, pmid = {29749696}, issn = {1462-2920}, abstract = {The thermoacidophilic Acidianus strain DS80 displays versatility in its energy metabolism and can grow autotrophically and heterotrophically with elemental sulfur (S°), ferric iron (Fe3+) or oxygen (O2) as electron acceptors. Here, we show that autotrophic and heterotrophic growth with S° as the electron acceptor is obligately dependent on hydrogen (H2) as electron donor; organic substrates such as acetate can only serve as a carbon source. In contrast, organic substrates such as acetate can serve as electron donor and carbon source for Fe3+ or O2 grown cells. During growth on S° or Fe3+ with H2 as an electron donor, the amount of CO2 assimilated into biomass decreased when cultures were provided with acetate. The addition of CO2 to cultures decreased the amount of acetate mineralized and assimilated and increased cell production in H2 /Fe3+ grown cells but had no effect on H2 /S° grown cells. In acetate/Fe3+ grown cells, the presence of H2 decreased the amount of acetate mineralized as CO2 in cultures compared to those without H2 . These results indicate that electron acceptor availability constrains the variety of carbon sources used by this strain. Addition of H2 to cultures overcomes this limitation and alters heterotrophic metabolism.}, } @article {pmid29749687, year = {2018}, author = {Falkowski, PG}, title = {Reverse engineering nature.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14241}, pmid = {29749687}, issn = {1462-2920}, } @article {pmid29749685, year = {2018}, author = {DeLong, EF and Inouye, DK}, title = {Thank You Ken, Joan and Dave, for 20 years of Environmental Microbiology!.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14243}, pmid = {29749685}, issn = {1462-2920}, } @article {pmid29749683, year = {2018}, author = {DeLong, EF and Inouye, DK}, title = {Towards a microbial universal theory of all (nearly) totality: MUTANT.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14242}, pmid = {29749683}, issn = {1462-2920}, } @article {pmid29749114, year = {2018}, author = {Toxopeus, J and Sinclair, BJ}, title = {Mechanisms underlying insect freeze tolerance.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1891-1914}, doi = {10.1111/brv.12425}, pmid = {29749114}, issn = {1469-185X}, abstract = {Freeze tolerance - the ability to survive internal ice formation - has evolved repeatedly in insects, facilitating survival in environments with low temperatures and/or high risk of freezing. Surviving internal ice formation poses several challenges because freezing can cause cellular dehydration and mechanical damage, and restricts the opportunity to metabolise and respond to environmental challenges. While freeze-tolerant insects accumulate many potentially protective molecules, there is no apparent 'magic bullet' - a molecule or class of molecules that appears to be necessary or sufficient to support this cold-tolerance strategy. In addition, the mechanisms underlying freeze tolerance have been minimally explored. Herein, we frame freeze tolerance as the ability to survive a process: freeze-tolerant insects must withstand the challenges associated with cooling (low temperatures), freezing (internal ice formation), and thawing. To do so, we hypothesise that freeze-tolerant insects control the quality and quantity of ice, prevent or repair damage to cells and macromolecules, manage biochemical processes while frozen/thawing, and restore physiological processes post-thaw. Many of the molecules that can facilitate freeze tolerance are also accumulated by other cold- and desiccation-tolerant insects. We suggest that, when freezing offered a physiological advantage, freeze tolerance evolved in insects that were already adapted to low temperatures or desiccation, or in insects that could withstand small amounts of internal ice formation. Although freeze tolerance is a complex cold-tolerance strategy that has evolved multiple times, we suggest that a process-focused approach (in combination with appropriate techniques and model organisms) will facilitate hypothesis-driven research to understand better how insects survive internal ice formation.}, } @article {pmid29748740, year = {2018}, author = {Tirumalai, MR and Tran, Q and Paci, M and Chavan, D and Marathe, A and Fox, GE}, title = {Exploration of RNA Sequence Space in the Absence of a Replicase.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {264-276}, pmid = {29748740}, issn = {1432-1432}, support = {11175//John Templeton Foundation (Via-Foundation for Applied Molecular Evolution)/ ; }, abstract = {It is generally considered that if an RNA World ever existed that it would be driven by an RNA capable of RNA replication. Whether such a catalytic RNA could emerge in an RNA World or not, there would need to be prior routes to increasing complexity in order to produce it. It is hypothesized here that increasing sequence variety, if not complexity, can in fact readily emerge in response to a dynamic equilibrium between synthesis and degradation. A model system in which T4 RNA ligase catalyzes synthesis and Benzonase catalyzes degradation was constructed. An initial 20-mer served as a seed and was subjected to 180 min of simultaneous ligation and degradation. The seed RNA rapidly disappeared and was replaced by an increasing number and variety of both larger and smaller variants. Variants of 40-80 residues were consistently seen, typically representing 2-4% of the unique sequences. In a second experiment with four individual 9-mers, numerous variants were again produced. These included variants of the individual 9-mers as well as sequences that contained sequence segments from two or more 9-mers. In both cases, the RNA products lack large numbers of point mutations but instead incorporate additions and subtractions of fragments of the original RNAs. The system demonstrates that if such equilibrium were established in a prebiotic world it would result in significant exploration of RNA sequence space and likely increased complexity. It remains to be seen if the variety of products produced is affected by the presence of small peptide oligomers.}, } @article {pmid29748575, year = {2018}, author = {Schmid, M and Jensen, TH}, title = {Controlling nuclear RNA levels.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {518-529}, doi = {10.1038/s41576-018-0013-2}, pmid = {29748575}, issn = {1471-0064}, abstract = {RNA turnover is an integral part of cellular RNA homeostasis and gene expression regulation. Whereas the cytoplasmic control of protein-coding mRNA is often the focus of study, we discuss here the less appreciated role of nuclear RNA decay systems in controlling RNA polymerase II (RNAPII)-derived transcripts. Historically, nuclear RNA degradation was found to be essential for the functionalization of transcripts through their proper maturation. Later, it was discovered to also be an important caretaker of nuclear hygiene by removing aberrant and unwanted transcripts. Recent years have now seen a set of new protein complexes handling a variety of new substrates, revealing functions beyond RNA processing and the decay of non-functional transcripts. This includes an active contribution of nuclear RNA metabolism to the overall cellular control of RNA levels, with mechanistic implications during cellular transitions.}, } @article {pmid29748429, year = {2018}, author = {Stirnemann, G and Jungwirth, P and Laage, D}, title = {Water dynamics in concentrated electrolytes: Local ion effect on hydrogen-bond jumps rather than collective coupling to ion clusters.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4953-E4954}, pmid = {29748429}, issn = {1091-6490}, } @article {pmid29748428, year = {2018}, author = {Zhang, Q and Wu, T and Chen, C and Mukamel, S and Zhuang, W}, title = {Reply to Stirnemann et al.: Frame retardation is the key reason behind the general slowdown of water reorientation dynamics in concentrated electrolytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4955-E4956}, pmid = {29748428}, issn = {1091-6490}, } @article {pmid29748324, year = {2018}, author = {Banerjee-Ghosh, K and Ben Dor, O and Tassinari, F and Capua, E and Yochelis, S and Capua, A and Yang, SH and Parkin, SSP and Sarkar, S and Kronik, L and Baczewski, LT and Naaman, R and Paltiel, Y}, title = {Separation of enantiomers by their enantiospecific interaction with achiral magnetic substrates.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1331-1334}, doi = {10.1126/science.aar4265}, pmid = {29748324}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {It is commonly assumed that recognition and discrimination of chirality, both in nature and in artificial systems, depend solely on spatial effects. However, recent studies have suggested that charge redistribution in chiral molecules manifests an enantiospecific preference in electron spin orientation. We therefore reasoned that the induced spin polarization may affect enantiorecognition through exchange interactions. Here we show experimentally that the interaction of chiral molecules with a perpendicularly magnetized substrate is enantiospecific. Thus, one enantiomer adsorbs preferentially when the magnetic dipole is pointing up, whereas the other adsorbs faster for the opposite alignment of the magnetization. The interaction is not controlled by the magnetic field per se, but rather by the electron spin orientations, and opens prospects for a distinct approach to enantiomeric separations.}, } @article {pmid29748323, year = {2018}, author = {Wang, T and Shi, Q and Nikkhoo, M and Wei, S and Barbot, S and Dreger, D and Bürgmann, R and Motagh, M and Chen, QF}, title = {The rise, collapse, and compaction of Mt. Mantap from the 3 September 2017 North Korean nuclear test.}, journal = {Science (New York, N.Y.)}, volume = {361}, number = {6398}, pages = {166-170}, doi = {10.1126/science.aar7230}, pmid = {29748323}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Surveillance of clandestine nuclear tests relies on a global seismic network, but the potential of spaceborne monitoring has been underexploited. We used satellite radar imagery to determine the complete surface displacement field of up to 3.5 meters of divergent horizontal motion with 0.5 meters of subsidence associated with North Korea's largest underground nuclear test. Combining insight from geodetic and seismological remote sensing, we found that the aftermath of the initial explosive deformation involved subsidence associated with subsurface collapse and aseismic compaction of the damaged rocks of the test site. The explosive yield from the nuclear detonation with best-fitting source parameters for 450-meter depth was 191 kilotonnes of TNT equivalent. Our results demonstrate the capability of spaceborne remote sensing to help characterize large underground nuclear tests.}, } @article {pmid29748322, year = {2018}, author = {Kellogg, EH and Hejab, NMA and Poepsel, S and Downing, KH and DiMaio, F and Nogales, E}, title = {Near-atomic model of microtubule-tau interactions.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1242-1246}, pmid = {29748322}, issn = {1095-9203}, support = {P01 GM051487/GM/NIGMS NIH HHS/United States ; K99 GM124463/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 GM123089/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; }, mesh = {Conserved Sequence ; Cryoelectron Microscopy ; Humans ; Microtubules/*chemistry ; *Models, Chemical ; Phosphorylation ; Phylogeny ; Polymerization ; Tandem Repeat Sequences ; tau Proteins/*chemistry/classification ; }, abstract = {Tau is a developmentally regulated axonal protein that stabilizes and bundles microtubules (MTs). Its hyperphosphorylation is thought to cause detachment from MTs and subsequent aggregation into fibrils implicated in Alzheimer's disease. It is unclear which tau residues are crucial for tau-MT interactions, where tau binds on MTs, and how it stabilizes them. We used cryo-electron microscopy to visualize different tau constructs on MTs and computational approaches to generate atomic models of tau-tubulin interactions. The conserved tubulin-binding repeats within tau adopt similar extended structures along the crest of the protofilament, stabilizing the interface between tubulin dimers. Our structures explain the effect of phosphorylation on MT affinity and lead to a model of tau repeats binding in tandem along protofilaments, tethering together tubulin dimers and stabilizing polymerization interfaces.}, } @article {pmid29748287, year = {2018}, author = {Li, S}, title = {Pitch imperfect.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {678}, doi = {10.1126/science.360.6389.678}, pmid = {29748287}, issn = {1095-9203}, } @article {pmid29748286, year = {2018}, author = {Chen, P and Tao, L and Wang, T and Zhang, J and He, A and Lam, KH and Liu, Z and He, X and Perry, K and Dong, M and Jin, R}, title = {Structural basis for recognition of frizzled proteins by Clostridium difficile toxin B.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {664-669}, pmid = {29748286}, issn = {1095-9203}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 NS080833/NS/NINDS NIH HHS/United States ; R01 GM057603/GM/NIGMS NIH HHS/United States ; R01 AI132387/AI/NIAID NIH HHS/United States ; P30 HD018655/HD/NICHD NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; R21 AI123920/AI/NIAID NIH HHS/United States ; R01 AI091823/AI/NIAID NIH HHS/United States ; R01 AI125704/AI/NIAID NIH HHS/United States ; R01 GM126120/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/metabolism ; Bacterial Toxins/*chemistry/metabolism ; Binding Sites ; Clostridium Infections/*metabolism ; Clostridium difficile/*pathogenicity ; Crystallography, X-Ray ; Fatty Acids/metabolism ; Frizzled Receptors/*chemistry ; Humans ; Protein Domains ; Virulence Factors/*chemistry/*metabolism ; Wnt Signaling Pathway ; }, abstract = {Clostridium difficile infection is the most common cause of antibiotic-associated diarrhea in developed countries. The major virulence factor, C. difficile toxin B (TcdB), targets colonic epithelia by binding to the frizzled (FZD) family of Wnt receptors, but how TcdB recognizes FZDs is unclear. Here, we present the crystal structure of a TcdB fragment in complex with the cysteine-rich domain of human FZD2 at 2.5-angstrom resolution, which reveals an endogenous FZD-bound fatty acid acting as a co-receptor for TcdB binding. This lipid occupies the binding site for Wnt-adducted palmitoleic acid in FZDs. TcdB binding locks the lipid in place, preventing Wnt from engaging FZDs and signaling. Our findings establish a central role of fatty acids in FZD-mediated TcdB pathogenesis and suggest strategies to modulate Wnt signaling.}, } @article {pmid29748285, year = {2018}, author = {Puchalski, RB and Shah, N and Miller, J and Dalley, R and Nomura, SR and Yoon, JG and Smith, KA and Lankerovich, M and Bertagnolli, D and Bickley, K and Boe, AF and Brouner, K and Butler, S and Caldejon, S and Chapin, M and Datta, S and Dee, N and Desta, T and Dolbeare, T and Dotson, N and Ebbert, A and Feng, D and Feng, X and Fisher, M and Gee, G and Goldy, J and Gourley, L and Gregor, BW and Gu, G and Hejazinia, N and Hohmann, J and Hothi, P and Howard, R and Joines, K and Kriedberg, A and Kuan, L and Lau, C and Lee, F and Lee, H and Lemon, T and Long, F and Mastan, N and Mott, E and Murthy, C and Ngo, K and Olson, E and Reding, M and Riley, Z and Rosen, D and Sandman, D and Shapovalova, N and Slaughterbeck, CR and Sodt, A and Stockdale, G and Szafer, A and Wakeman, W and Wohnoutka, PE and White, SJ and Marsh, D and Rostomily, RC and Ng, L and Dang, C and Jones, A and Keogh, B and Gittleman, HR and Barnholtz-Sloan, JS and Cimino, PJ and Uppin, MS and Keene, CD and Farrokhi, FR and Lathia, JD and Berens, ME and Iavarone, A and Bernard, A and Lein, E and Phillips, JW and Rostad, SW and Cobbs, C and Hawrylycz, MJ and Foltz, GD}, title = {An anatomic transcriptional atlas of human glioblastoma.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {660-663}, doi = {10.1126/science.aaf2666}, pmid = {29748285}, issn = {1095-9203}, support = {R01 CA136808/CA/NCI NIH HHS/United States ; R01 CA179044/CA/NCI NIH HHS/United States ; R01 CA178546/CA/NCI NIH HHS/United States ; R01 CA190891/CA/NCI NIH HHS/United States ; U54 CA193313/CA/NCI NIH HHS/United States ; R01 NS091251/NS/NINDS NIH HHS/United States ; R01 NS061776/NS/NINDS NIH HHS/United States ; }, mesh = {Atlases as Topic ; Brain Neoplasms/*genetics/*pathology ; Databases, Genetic ; Gene Expression Profiling ; Glioblastoma/*genetics/*pathology ; Humans ; Prognosis ; }, abstract = {Glioblastoma is an aggressive brain tumor that carries a poor prognosis. The tumor's molecular and cellular landscapes are complex, and their relationships to histologic features routinely used for diagnosis are unclear. We present the Ivy Glioblastoma Atlas, an anatomically based transcriptional atlas of human glioblastoma that aligns individual histologic features with genomic alterations and gene expression patterns, thus assigning molecular information to the most important morphologic hallmarks of the tumor. The atlas and its clinical and genomic database are freely accessible online data resources that will serve as a valuable platform for future investigations of glioblastoma pathogenesis, diagnosis, and treatment.}, } @article {pmid29748284, year = {2018}, author = {Sims, CR}, title = {Efficient coding explains the universal law of generalization in human perception.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {652-656}, doi = {10.1126/science.aaq1118}, pmid = {29748284}, issn = {1095-9203}, mesh = {Cognition ; *Generalization, Response ; Humans ; Learning ; Models, Psychological ; *Perception ; }, abstract = {Perceptual generalization and discrimination are fundamental cognitive abilities. For example, if a bird eats a poisonous butterfly, it will learn to avoid preying on that species again by generalizing its past experience to new perceptual stimuli. In cognitive science, the "universal law of generalization" seeks to explain this ability and states that generalization between stimuli will follow an exponential function of their distance in "psychological space." Here, I challenge existing theoretical explanations for the universal law and offer an alternative account based on the principle of efficient coding. I show that the universal law emerges inevitably from any information processing system (whether biological or artificial) that minimizes the cost of perceptual error subject to constraints on the ability to process or transmit information.}, } @article {pmid29748283, year = {2018}, author = {Ge, C and Ye, J and Weber, C and Sun, W and Zhang, H and Zhou, Y and Cai, C and Qian, G and Capel, B}, title = {The histone demethylase KDM6B regulates temperature-dependent sex determination in a turtle species.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {645-648}, doi = {10.1126/science.aap8328}, pmid = {29748283}, issn = {1095-9203}, mesh = {Animals ; DNA Methylation ; Female ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; Histones/*metabolism ; Jumonji Domain-Containing Histone Demethylases/*metabolism ; Male ; Ovum/growth & development ; Promoter Regions, Genetic ; Sex Determination Processes/*genetics ; *Temperature ; Transcription Factors/genetics ; Turtles/*embryology/*genetics ; }, abstract = {Temperature-dependent sex determination is a notable model of phenotypic plasticity. In many reptiles, including the red-eared slider turtle Trachemys scripta elegans (T. scripta), the individual's sex is determined by the ambient temperature during egg incubation. In this study, we show that the histone H3 lysine 27 (H3K27) demethylase KDM6B exhibits temperature-dependent sexually dimorphic expression in early T. scripta embryos before the gonad is distinct. Knockdown of Kdm6b at 26°C (a temperature at which all offspring develop into males) triggers male-to-female sex reversal in >80% of surviving embryos. KDM6B directly promotes the transcription of the male sex-determining gene Dmrt1 by eliminating the trimethylation of H3K27 near its promoter. Additionally, overexpression of Dmrt1 is sufficient to rescue the sex reversal induced by disruption of Kdm6b This study establishes causality and a direct genetic link between epigenetic mechanisms and temperature-dependent sex determination in a turtle species.}, } @article {pmid29748282, year = {2018}, author = {Barneche, DR and Robertson, DR and White, CR and Marshall, DJ}, title = {Fish reproductive-energy output increases disproportionately with body size.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {642-645}, doi = {10.1126/science.aao6868}, pmid = {29748282}, issn = {1095-9203}, mesh = {Animals ; *Body Size ; Female ; *Fertility ; Fisheries ; Fishes/*anatomy & histology/*physiology ; *Reproduction ; }, abstract = {Body size determines total reproductive-energy output. Most theories assume reproductive output is a fixed proportion of size, with respect to mass, but formal macroecological tests are lacking. Management based on that assumption risks underestimating the contribution of larger mothers to replenishment, hindering sustainable harvesting. We test this assumption in marine fishes with a phylogenetically controlled meta-analysis of the intraspecific mass scaling of reproductive-energy output. We show that larger mothers reproduce disproportionately more than smaller mothers in not only fecundity but also total reproductive energy. Our results reset much of the theory on how reproduction scales with size and suggest that larger mothers contribute disproportionately to population replenishment. Global change and overharvesting cause fish sizes to decline; our results provide quantitative estimates of how these declines affect fisheries and ecosystem-level productivity.}, } @article {pmid29748281, year = {2018}, author = {Pupo, G and Ibba, F and Ascough, DMH and Vicini, AC and Ricci, P and Christensen, KE and Pfeifer, L and Morphy, JR and Brown, JM and Paton, RS and Gouverneur, V}, title = {Asymmetric nucleophilic fluorination under hydrogen bonding phase-transfer catalysis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {638-642}, doi = {10.1126/science.aar7941}, pmid = {29748281}, issn = {1095-9203}, abstract = {Common anionic nucleophiles such as those derived from inorganic salts have not been used for enantioselective catalysis because of their insolubility. Here, we report that merging hydrogen bonding and phase-transfer catalysis provides an effective mode of activation for nucleophiles that are insoluble in organic solvents. This catalytic manifold relies on hydrogen bonding complexation to render nucleophiles soluble and reactive, while simultaneously inducing asymmetry in the ensuing transformation. We demonstrate the concept using a chiral bis-urea catalyst to form a tridentate hydrogen bonding complex with fluoride from its cesium salt, thereby enabling highly efficient enantioselective ring opening of episulfonium ion. This fluorination method is synthetically valuable considering the scarcity of alternative protocols and points the way to wider application of the catalytic approach with diverse anionic nucleophiles.}, } @article {pmid29748280, year = {2018}, author = {Tritsis, A and Tassis, K}, title = {Magnetic seismology of interstellar gas clouds: Unveiling a hidden dimension.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {635-638}, doi = {10.1126/science.aao1185}, pmid = {29748280}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Stars and planets are formed inside dense interstellar molecular clouds by processes imprinted on the three-dimensional (3D) morphology of the clouds. Determining the 3D structure of interstellar clouds remains challenging because of projection effects and difficulties measuring the extent of the clouds along the line of sight. We report the detection of normal vibrational modes in the isolated interstellar cloud Musca, allowing determination of the 3D physical dimensions of the cloud. We found that Musca is vibrating globally, with the characteristic modes of a sheet viewed edge on, not the characteristics of a filament as previously supposed. We reconstructed the physical properties of Musca through 3D magnetohydrodynamic simulations, reproducing the observed normal modes and confirming a sheetlike morphology.}, } @article {pmid29748279, year = {2018}, author = {Lipton, JI and MacCurdy, R and Manchester, Z and Chin, L and Cellucci, D and Rus, D}, title = {Handedness in shearing auxetics creates rigid and compliant structures.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {632-635}, doi = {10.1126/science.aar4586}, pmid = {29748279}, issn = {1095-9203}, abstract = {In nature, repeated base units produce handed structures that selectively bond to make rigid or compliant materials. Auxetic tilings are scale-independent frameworks made from repeated unit cells that expand under tension. We discovered how to produce handedness in auxetic unit cells that shear as they expand by changing the symmetries and alignments of auxetic tilings. Using the symmetry and alignment rules that we developed, we made handed shearing auxetics that tile planes, cylinders, and spheres. By compositing the handed shearing auxetics in a manner inspired by keratin and collagen, we produce both compliant structures that expand while twisting and deployable structures that can rigidly lock. This work opens up new possibilities in designing chemical frameworks, medical devices like stents, robotic systems, and deployable engineering structures.}, } @article {pmid29748278, year = {2018}, author = {O'Hanlon, SJ and Rieux, A and Farrer, RA and Rosa, GM and Waldman, B and Bataille, A and Kosch, TA and Murray, KA and Brankovics, B and Fumagalli, M and Martin, MD and Wales, N and Alvarado-Rybak, M and Bates, KA and Berger, L and Böll, S and Brookes, L and Clare, F and Courtois, EA and Cunningham, AA and Doherty-Bone, TM and Ghosh, P and Gower, DJ and Hintz, WE and Höglund, J and Jenkinson, TS and Lin, CF and Laurila, A and Loyau, A and Martel, A and Meurling, S and Miaud, C and Minting, P and Pasmans, F and Schmeller, DS and Schmidt, BR and Shelton, JMG and Skerratt, LF and Smith, F and Soto-Azat, C and Spagnoletti, M and Tessa, G and Toledo, LF and Valenzuela-Sánchez, A and Verster, R and Vörös, J and Webb, RJ and Wierzbicki, C and Wombwell, E and Zamudio, KR and Aanensen, DM and James, TY and Gilbert, MTP and Weldon, C and Bosch, J and Balloux, F and Garner, TWJ and Fisher, MC}, title = {Recent Asian origin of chytrid fungi causing global amphibian declines.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {621-627}, doi = {10.1126/science.aar1965}, pmid = {29748278}, issn = {1095-9203}, support = {BB/E023207/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Africa ; Americas ; Amphibians/*microbiology ; Animals ; Asia ; Australia ; Chytridiomycota/classification/genetics/isolation & purification/pathogenicity ; Europe ; *Extinction, Biological ; Genes, Fungal ; Genetic Variation ; Hybridization, Genetic ; Korea ; Phylogeny ; Sequence Analysis, DNA ; Virulence ; }, abstract = {Globalized infectious diseases are causing species declines worldwide, but their source often remains elusive. We used whole-genome sequencing to solve the spatiotemporal origins of the most devastating panzootic to date, caused by the fungus Batrachochytrium dendrobatidis, a proximate driver of global amphibian declines. We traced the source of B. dendrobatidis to the Korean peninsula, where one lineage, BdASIA-1, exhibits the genetic hallmarks of an ancestral population that seeded the panzootic. We date the emergence of this pathogen to the early 20th century, coinciding with the global expansion of commercial trade in amphibians, and we show that intercontinental transmission is ongoing. Our findings point to East Asia as a geographic hotspot for B. dendrobatidis biodiversity and the original source of these lineages that now parasitize amphibians worldwide.}, } @article {pmid29748277, year = {2018}, author = {Buma, B}, title = {The hidden value of paper records.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {613}, doi = {10.1126/science.aat5382}, pmid = {29748277}, issn = {1095-9203}, } @article {pmid29748276, year = {2018}, author = {Mateo-Tomás, P and Olea, PP and López-Bao, JV}, title = {Europe's uneven laws threaten scavengers.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {612-613}, doi = {10.1126/science.aat8492}, pmid = {29748276}, issn = {1095-9203}, mesh = {Animals ; Birds ; Cattle ; *Conservation of Natural Resources ; Encephalopathy, Bovine Spongiform/*prevention & control ; Europe ; European Union ; Feeding Behavior ; Policy ; Sanitation/*legislation & jurisprudence ; }, } @article {pmid29748275, year = {2018}, author = {Alarcón, PAE and Lambertucci, SA}, title = {Pesticides thwart condor conservation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {612}, doi = {10.1126/science.aat6039}, pmid = {29748275}, issn = {1095-9203}, mesh = {Animals ; Argentina ; *Birds ; Carbofuran/*poisoning ; *Conservation of Natural Resources ; Insecticides/*poisoning ; Population ; }, } @article {pmid29748274, year = {2018}, author = {Selin, NE}, title = {A proposed global metric to aid mercury pollution policy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {607-609}, doi = {10.1126/science.aar8256}, pmid = {29748274}, issn = {1095-9203}, mesh = {Animals ; Environmental Exposure/*prevention & control/standards ; Environmental Pollution/*prevention & control ; Fishes ; Great Lakes Region ; Mercury/analysis/*standards/toxicity ; Methylmercury Compounds/analysis/*standards/toxicity ; Policy ; }, } @article {pmid29748273, year = {2018}, author = {Mumm, P}, title = {Resolving the neutron lifetime puzzle.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {605-606}, doi = {10.1126/science.aat7140}, pmid = {29748273}, issn = {1095-9203}, } @article {pmid29748272, year = {2018}, author = {Lips, K}, title = {The hidden biodiversity of amphibian pathogens.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {604-605}, doi = {10.1126/science.aat6411}, pmid = {29748272}, issn = {1095-9203}, mesh = {*Amphibians ; Animals ; *Biodiversity ; Chytridiomycota ; }, } @article {pmid29748271, year = {2018}, author = {Trefely, S and Wellen, KE}, title = {Metabolite regulates differentiation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {603-604}, doi = {10.1126/science.aat6663}, pmid = {29748271}, issn = {1095-9203}, mesh = {*Cell Differentiation ; }, } @article {pmid29748270, year = {2018}, author = {Georges, A and Holleley, CE}, title = {How does temperature determine sex?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {601-602}, doi = {10.1126/science.aat5993}, pmid = {29748270}, issn = {1095-9203}, mesh = {Animals ; *Sex Determination Processes ; Sex Ratio ; *Temperature ; Turtles ; }, } @article {pmid29748269, year = {2018}, author = {Kane, PM}, title = {Energy powerhouses of cells come into focus.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {600-601}, doi = {10.1126/science.aat6275}, pmid = {29748269}, issn = {1095-9203}, mesh = {*Cell Count ; Humans ; *Mitochondria ; Physical Phenomena ; }, } @article {pmid29748268, year = {2018}, author = {Candela, T and Wassing, B and Ter Heege, J and Buijze, L}, title = {How earthquakes are induced.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {598-600}, doi = {10.1126/science.aat2776}, pmid = {29748268}, issn = {1095-9203}, } @article {pmid29748267, year = {2018}, author = {Leslie, M}, title = {Small but mighty.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {594-597}, doi = {10.1126/science.360.6389.594}, pmid = {29748267}, issn = {1095-9203}, mesh = {Animals ; Antibodies/chemistry/*immunology/isolation & purification/therapeutic use ; Biomedical Research/trends ; Camelus/*immunology ; Humans ; Protein Conformation ; Sharks/*immunology ; }, } @article {pmid29748266, year = {2018}, author = {Langin, K}, title = {A different animal.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {590-592}, doi = {10.1126/science.360.6389.590}, pmid = {29748266}, issn = {1095-9203}, mesh = {Animals ; California ; *Endangered Species ; Oncorhynchus/*genetics ; Rivers ; Seasons ; }, } @article {pmid29748265, year = {2018}, author = {Sokol, J}, title = {Fast stars point to supernovae, black holes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {589}, doi = {10.1126/science.360.6389.589}, pmid = {29748265}, issn = {1095-9203}, } @article {pmid29748264, year = {2018}, author = {Garber, K}, title = {A new cancer immunotherapy suffers a setback.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {588}, doi = {10.1126/science.360.6389.588}, pmid = {29748264}, issn = {1095-9203}, mesh = {Clinical Trials, Phase III as Topic ; Drug Industry ; Humans ; *Immunotherapy ; Neoplasms/*drug therapy ; Oximes/*therapeutic use ; Sulfonamides/*therapeutic use ; Treatment Failure ; }, } @article {pmid29748263, year = {2018}, author = {Price, M}, title = {Finding the first horse tamers.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {587}, doi = {10.1126/science.360.6389.587}, pmid = {29748263}, issn = {1095-9203}, mesh = {Animals ; Asian Continental Ancestry Group/*genetics ; *Domestication ; European Continental Ancestry Group/*genetics ; History, Ancient ; *Horses ; *Human Migration/history ; Humans ; Kazakhstan ; }, } @article {pmid29748262, year = {2018}, author = {Voosen, P}, title = {NASA cancels carbon monitoring research program.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {586-587}, doi = {10.1126/science.360.6389.586}, pmid = {29748262}, issn = {1095-9203}, } @article {pmid29748261, year = {2018}, author = {Zainzinger, V}, title = {Animal tests surge under new U.S. chemical law.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {585-586}, doi = {10.1126/science.360.6389.585}, pmid = {29748261}, issn = {1095-9203}, mesh = {Animal Experimentation/*legislation & jurisprudence ; *Animal Welfare ; Animals ; Chemical Safety/*legislation & jurisprudence ; Federal Government ; United States ; United States Environmental Protection Agency ; }, } @article {pmid29748260, year = {2018}, author = {Karáth, K}, title = {Hungarian science troubled by nationalism.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {584-585}, doi = {10.1126/science.360.6389.584}, pmid = {29748260}, issn = {1095-9203}, } @article {pmid29748259, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {582-583}, doi = {10.1126/science.360.6389.582}, pmid = {29748259}, issn = {1095-9203}, } @article {pmid29748258, year = {2018}, author = {Zerbo, L}, title = {Backing up nuclear disarmament.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {581}, doi = {10.1126/science.aau0693}, pmid = {29748258}, issn = {1095-9203}, } @article {pmid29748257, year = {2018}, author = {Ryu, KW and Nandu, T and Kim, J and Challa, S and DeBerardinis, RJ and Kraus, WL}, title = {Metabolic regulation of transcription through compartmentalized NAD+ biosynthesis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {}, doi = {10.1126/science.aan5780}, pmid = {29748257}, issn = {1095-9203}, support = {R01 DK069710/DK/NIDDK NIH HHS/United States ; R01 DK058110/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adipocytes/*cytology/metabolism ; Adipogenesis/*genetics ; Animals ; CCAAT-Enhancer-Binding Protein-beta ; Cell Line, Tumor ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Glucose/metabolism ; Humans ; Mice ; NAD/*biosynthesis/genetics ; NIH 3T3 Cells ; Nicotinamide-Nucleotide Adenylyltransferase/*metabolism ; Poly (ADP-Ribose) Polymerase-1/metabolism ; Substrate Specificity ; *Transcription, Genetic ; }, abstract = {NAD+ (nicotinamide adenine dinucleotide in its oxidized state) is an essential molecule for a variety of physiological processes. It is synthesized in distinct subcellular compartments by three different synthases (NMNAT-1, -2, and -3). We found that compartmentalized NAD+ synthesis by NMNATs integrates glucose metabolism and adipogenic transcription during adipocyte differentiation. Adipogenic signaling rapidly induces cytoplasmic NMNAT-2, which competes with nuclear NMNAT-1 for the common substrate, nicotinamide mononucleotide, leading to a precipitous reduction in nuclear NAD+ levels. This inhibits the catalytic activity of poly[adenosine diphosphate (ADP)-ribose] polymerase-1 (PARP-1), a NAD+-dependent enzyme that represses adipogenic transcription by ADP-ribosylating the adipogenic transcription factor C/EBPβ. Reversal of PARP-1-mediated repression by NMNAT-2-mediated nuclear NAD+ depletion in response to adipogenic signals drives adipogenesis. Thus, compartmentalized NAD+ synthesis functions as an integrator of cellular metabolism and signal-dependent transcriptional programs.}, } @article {pmid29748256, year = {2018}, author = {Hahn, A and Vonck, J and Mills, DJ and Meier, T and Kühlbrandt, W}, title = {Structure, mechanism, and regulation of the chloroplast ATP synthase.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {}, doi = {10.1126/science.aat4318}, pmid = {29748256}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Adenosine Triphosphate ; Chloroplast Proton-Translocating ATPases/*chemistry/*metabolism ; Chloroplasts/*enzymology ; Cryoelectron Microscopy ; Evolution, Molecular ; Molecular Motor Proteins/*chemistry/*metabolism ; Plant Leaves/enzymology ; Protein Conformation ; Protein Subunits/chemistry/metabolism ; Rotation ; Spinacia oleracea/enzymology ; }, abstract = {The chloroplast adenosine triphosphate (ATP) synthase uses the electrochemical proton gradient generated by photosynthesis to produce ATP, the energy currency of all cells. Protons conducted through the membrane-embedded Fo motor drive ATP synthesis in the F1 head by rotary catalysis. We determined the high-resolution structure of the complete cF1Fo complex by cryo-electron microscopy, resolving side chains of all 26 protein subunits, the five nucleotides in the F1 head, and the proton pathway to and from the rotor ring. The flexible peripheral stalk redistributes differences in torsional energy across three unequal steps in the rotation cycle. Plant ATP synthase is autoinhibited by a β-hairpin redox switch in subunit γ that blocks rotation in the dark.}, } @article {pmid29748042, year = {2018}, author = {Gil, MA and Hein, AM and Spiegel, O and Baskett, ML and Sih, A}, title = {Social Information Links Individual Behavior to Population and Community Dynamics.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {535-548}, doi = {10.1016/j.tree.2018.04.010}, pmid = {29748042}, issn = {1872-8383}, abstract = {When individual animals make decisions, they routinely use information produced intentionally or unintentionally by other individuals. Despite its prevalence and established fitness consequences, the effects of such social information on ecological dynamics remain poorly understood. Here, we synthesize results from ecology, evolutionary biology, and animal behavior to show how the use of social information can profoundly influence the dynamics of populations and communities. We combine recent theoretical and empirical results and introduce simple population models to illustrate how social information use can drive positive density-dependent growth of populations and communities (Allee effects). Furthermore, social information can shift the nature and strength of species interactions, change the outcome of competition, and potentially increase extinction risk in harvested populations and communities.}, } @article {pmid29747698, year = {2018}, author = {Assemie, MA and Muchie, KF and Ayele, TA}, title = {Incidence and predictors of loss to follow up among HIV-infected adults at Pawi General Hospital, northwest Ethiopia: competing risk regression model.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {287}, pmid = {29747698}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Demography ; Ethiopia/epidemiology ; Female ; Follow-Up Studies ; HIV Infections/*epidemiology ; *Hospitals, General ; Humans ; Incidence ; Male ; Middle Aged ; Multivariate Analysis ; Regression Analysis ; Risk Factors ; Young Adult ; }, abstract = {OBJECTIVE: This study was aimed at assessing the incidence of lost-to-follow-up and its predictors among HIV-positive adults after initiation into antiretroviral therapy at Pawi General Hospital, northwest Ethiopia.

RESULTS: The overall cumulative incidence of lost-to-follow-up after ART initiation was high, 11.6 (95% CI 9.8-13.7) per 100 adult-years follow-up time. Independent significant predictors of lost to follow up were being aged 15-28 years (aSHR = 0.44; 95% CI 0.24-0.83), being on WHO clinical stage IV (aSHR = 2.09; 95% CI 1.02-3.13); and receiving isoniazid preventive therapy (aSHR = 0.11; 95% CI 0.06-0.18).}, } @article {pmid29747692, year = {2018}, author = {Benjamino, J and Lincoln, S and Srivastava, R and Graf, J}, title = {Low-abundant bacteria drive compositional changes in the gut microbiota after dietary alteration.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {86}, pmid = {29747692}, issn = {2049-2618}, support = {1137249//National Science Foundation/International ; }, mesh = {Animals ; Bacteria/*classification/genetics/isolation & purification ; Base Sequence ; DNA, Bacterial/genetics ; Diet ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Isoptera/*microbiology ; Lignin/metabolism ; Sequence Analysis, DNA ; Symbiosis/physiology ; }, abstract = {BACKGROUND: As the importance of beneficial bacteria is better recognized, understanding the dynamics of symbioses becomes increasingly crucial. In many gut symbioses, it is essential to understand whether changes in host diet play a role in the persistence of the bacterial gut community. In this study, termites were fed six dietary sources and the microbial community was monitored over a 49-day period using 16S rRNA gene sequencing. A deep backpropagation artificial neural network (ANN) was used to learn how the six different lignocellulose food sources affected the temporal composition of the hindgut microbiota of the termite as well as taxon-taxon and taxon-substrate interactions.

RESULTS: Shifts in the termite gut microbiota after diet change in each colony were observed using 16S rRNA gene sequencing and beta diversity analyses. The artificial neural network accurately predicted the relative abundances of taxa at random points in the temporal study and showed that low-abundant taxa maintain community driving correlations in the hindgut.

CONCLUSIONS: This combinatorial approach utilizing 16S rRNA gene sequencing and deep learning revealed that low-abundant bacteria that often do not belong to the core community are drivers of the termite hindgut bacterial community composition.}, } @article {pmid29747687, year = {2018}, author = {Hashmi, AA and Hussain, ZF and Qadri, A and Irfan, M and Ramzan, S and Faridi, N and Khan, A and Edhi, MM}, title = {Androgen receptor expression in endometrial carcinoma and its correlation with clinicopathologic features.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {289}, pmid = {29747687}, issn = {1756-0500}, mesh = {Demography ; Endometrial Neoplasms/*pathology ; Female ; Humans ; Middle Aged ; Receptors, Androgen/*metabolism ; }, abstract = {OBJECTIVES: Recent evidence suggests a role of androgen receptor expression as a prognostic and therapeutic biomarker in endometrial carcinoma, therefore in the present study we aimed to evaluate the frequency of androgen expression in different subtypes of endometrial carcinoma and its association with clinic-pathologic features.

RESULTS: 18/89 (20.2%) cases of endometrial carcinoma showed positive androgen receptor expression. On the other hand, low, moderate and high androgen receptor expression was noted in 7/89 (7.9%), 10/89 (11.2%) and 1/89 (1.1%) cases respectively. 15/77 (19.48%) of endometrioid cancers and 3/7 (42.28%) cases of serous carcinoma showed androgen receptor expression; while none of the cases of clear cell or carcinosarcoma revealed androgen receptor expression. No significant association of androgen receptor expression with various clinicopathologic features of endometrial carcinoma was noted. We found that a significant subset of endometrial cancers express androgen receptor especially a serous cancers; therefore we suggest that androgen receptor expression testing should be done in endometrial carcinoma.}, } @article {pmid29747679, year = {2018}, author = {Zhao, K and Margaria, P and Rosa, C}, title = {Characterization of the first complete genome sequence of an Impatiens necrotic spot orthotospovirus isolate from the United States and worldwide phylogenetic analyses of INSV isolates.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {288}, pmid = {29747679}, issn = {1756-0500}, mesh = {Base Sequence ; Conserved Sequence/genetics ; Genetic Vectors/metabolism ; *Genome, Viral ; Host-Pathogen Interactions/genetics ; Nucleotide Motifs/genetics ; *Phylogeny ; Plant Diseases/virology ; Recombination, Genetic ; Tospovirus/*genetics/*isolation & purification ; United States ; }, abstract = {OBJECTIVE: Impatiens necrotic spot orthotospovirus (INSV) can impact economically important ornamental plants and vegetables worldwide. Characterization studies on INSV are limited. For most INSV isolates, there are no complete genome sequences available. This lack of genomic information has a negative impact on the understanding of the INSV genetic diversity and evolution. Here we report the first complete nucleotide sequence of a US INSV isolate.

RESULTS: INSV-UP01 was isolated from an impatiens in Pennsylvania, US. RT-PCR was used to clone its full-length genome and Vector NTI to assemble overlapping sequences. Phylogenetic trees were constructed by using MEGA7 software to show the phylogenetic relationships with other available INSV sequences worldwide. This US isolate has genome and biological features classical of INSV species and clusters in the Western Hemisphere clade, but its origin appears to be recent. Furthermore, INSV-UP01 might have been involved in a recombination event with an Italian isolate belonging to the Asian clade. Our analyses support that INSV isolates infect a broad plant-host range they group by geographic origin and not by host, and are subjected to frequent recombination events. These results justify the need to generate and analyze complete genome sequences of orthotospoviruses in general and INSV in particular.}, } @article {pmid29747590, year = {2018}, author = {Hui, M and Cheng, J and Sha, Z}, title = {First comprehensive analysis of lysine acetylation in Alvinocaris longirostris from the deep-sea hydrothermal vents.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {352}, pmid = {29747590}, issn = {1471-2164}, support = {QYZDB-SSW-DQC036//Key Research Program of Frontier Sciences, Chinese Academy of Sciences/ ; XDA1103040102//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; }, mesh = {Acetylation ; Adaptation, Physiological ; Amino Acid Sequence ; Animals ; Arthropod Proteins/chemistry/metabolism ; Chromatography, High Pressure Liquid ; Decapoda (Crustacea)/*metabolism/microbiology/physiology ; Hemocyanins/chemistry/metabolism ; *Hydrothermal Vents ; Lysine/*metabolism ; Mitochondria/metabolism ; Peptides/metabolism ; Peroxisomes/metabolism ; Sequence Homology, Amino Acid ; Stress, Physiological ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Deep-sea hydrothermal vents are unique chemoautotrophic ecosystems with harsh conditions. Alvinocaris longirostris is one of the dominant crustacean species inhabiting in these extreme environments. It is significant to clarify mechanisms in their adaptation to the vents. Lysine acetylation has been known to play critical roles in the regulation of many cellular processes. However, its function in A. longirostris and even marine invertebrates remains elusive. Our study is the first, to our knowledge, to comprehensively investigate lysine acetylome in A. longirostris.

RESULTS: In total, 501 unique acetylation sites from 206 proteins were identified by combination of affinity enrichment and high-sensitive-massspectrometer. It was revealed that Arg, His and Lys occurred most frequently at the + 1 position downstream of the acetylation sites, which were all alkaline amino acids and positively charged. Functional analysis revealed that the protein acetylation was involved in diverse cellular processes, such as biosynthesis of amino acids, citrate cycle, fatty acid degradation and oxidative phosphorylation. Acetylated proteins were found enriched in mitochondrion and peroxisome, and many stress response related proteins were also discovered to be acetylated, like arginine kinases, heat shock protein 70, and hemocyanins. In the two hemocyanins, nine acetylation sites were identified, among which one acetylation site was unique in A. longirostris when compared with other shallow water shrimps. Further studies are warranted to verify its function.

CONCLUSION: The lysine acetylome of A. longirostris is investigated for the first time and brings new insights into the regulation function of the lysine acetylation. The results supply abundant resources for exploring the functions of acetylation in A. longirostris and other shrimps.}, } @article {pmid29747589, year = {2018}, author = {Kurucz, V and Krüger, T and Antal, K and Dietl, AM and Haas, H and Pócsi, I and Kniemeyer, O and Emri, T}, title = {Additional oxidative stress reroutes the global response of Aspergillus fumigatus to iron depletion.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {357}, pmid = {29747589}, issn = {1471-2164}, support = {K112181//National Research, Development and Innovation Office/ ; Transregio124 (project Z2)//Collaborative Research Centre (DFG)/ ; 91529720-50015537//German Academic Exchange Service (DAAD)/ ; B2/1F/7506//Campus Hungary/ ; FWF grant I1616/Infect-ERA project AspMetNet//Austrian Science Fund/ ; W1253//HOROS doctoral program/ ; EFOP-3.6.1-16-2016-00022//European Union and the European Social Fund/ ; Biotechnology thematic programme of the University of Debrecen//Higher Education Institutional Excellence Programme of the Ministry of Human Capacities in Hungary/ ; }, mesh = {Aspergillus fumigatus/drug effects/genetics/growth & development/*metabolism ; Chromatography, Liquid ; Fungal Proteins/metabolism ; Host-Pathogen Interactions ; Hydrogen Peroxide/*pharmacology ; Iron/*metabolism ; Oxidative Stress/*drug effects ; Proteomics ; Real-Time Polymerase Chain Reaction ; Reverse Transcriptase Polymerase Chain Reaction ; Tandem Mass Spectrometry ; Transcriptome ; }, abstract = {BACKGROUND: Aspergillus fumigatus has to cope with a combination of several stress types while colonizing the human body. A functional interplay between these different stress responses can increase the chances of survival for this opportunistic human pathogen during the invasion of its host. In this study, we shed light on how the H2O2-induced oxidative stress response depends on the iron available to this filamentous fungus, using transcriptomic analysis, proteomic profiles, and growth assays.

RESULTS: The applied H2O2 treatment, which induced only a negligible stress response in iron-replete cultures, deleteriously affected the fungus under iron deprivation. The majority of stress-induced changes in gene and protein expression was not predictable from data coming from individual stress exposure and was only characteristic for the combination of oxidative stress plus iron deprivation. Our experimental data suggest that the physiological effects of combined stresses and the survival of the fungus highly depend on fragile balances between economization of iron and production of essential iron-containing proteins. One observed strategy was the overproduction of iron-independent antioxidant proteins to combat oxidative stress during iron deprivation, e.g. the upregulation of superoxide dismutase Sod1, the thioredoxin reductase Trr1, and the thioredoxin orthologue Afu5g11320. On the other hand, oxidative stress induction overruled iron deprivation-mediated repression of several genes. In agreement with the gene expression data, growth studies underlined that in A. fumigatus iron deprivation aggravates oxidative stress susceptibility.

CONCLUSIONS: Our data demonstrate that studying stress responses under separate single stress conditions is not sufficient to understand how A. fumigatus adapts in a complex and hostile habitat like the human body. The combinatorial stress of iron depletion and hydrogen peroxide caused clear non-additive effects upon the stress response of A. fumigatus. Our data further supported the view that the ability of A. fumigatus to cause diseases in humans strongly depends on its fitness attributes and less on specific virulence factors. In summary, A. fumigatus is able to mount and coordinate complex and efficient responses to combined stresses like iron deprivation plus H2O2-induced oxidative stress, which are exploited by immune cells to kill fungal pathogens.}, } @article {pmid29747587, year = {2018}, author = {Biase, FH and Kimble, KM}, title = {Functional signaling and gene regulatory networks between the oocyte and the surrounding cumulus cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {351}, pmid = {29747587}, issn = {1471-2164}, mesh = {Animals ; Cattle ; Cell Compartmentation ; Cumulus Cells/*metabolism ; Female ; Gene Expression Profiling ; *Gene Regulatory Networks ; Ligands ; Oocytes/*metabolism ; *Signal Transduction ; Transcriptome ; }, abstract = {BACKGROUND: The maturation and successful acquisition of developmental competence by an oocyte, the female gamete, during folliculogenesis is highly dependent on molecular interactions with somatic cells. Most of the cellular interactions identified, thus far, are modulated by growth factors, ions or metabolites. We hypothesized that this interaction is also modulated at the transcriptional level, which leads to the formation of gene regulatory networks between the oocyte and cumulus cells. We tested this hypothesis by analyzing transcriptome data from single oocytes and the surrounding cumulus cells collected from antral follicles employing an analytical framework to determine interdependencies at the transcript level.

RESULTS: We overlapped our transcriptome data with putative protein-protein interactions and identified hundreds of ligand-receptor pairs that can transduce paracrine signaling between an oocyte and cumulus cells. We determined that 499 ligand-encoding genes expressed in oocytes and cumulus cells are functionally associated with transcription regulation (FDR < 0.05). Ligand-encoding genes with specific expression in oocytes or cumulus cells were enriched for biological functions that are likely associated with the coordinated formation of transzonal projections from cumulus cells that reach the oocyte's membrane. Thousands of gene pairs exhibit significant linear co-expression (absolute correlation > 0.85, FDR < 1.8 × 10- 5) patterns between oocytes and cumulus cells. Hundreds of co-expressing genes showed clustering patterns associated with biological functions (FDR < 0.5) necessary for a coordinated function between the oocyte and cumulus cells during folliculogenesis (i.e. regulation of transcription, translation, apoptosis, cell differentiation and transport).

CONCLUSION: Our analyses revealed a complex and functional gene regulatory circuit between the oocyte and surrounding cumulus cells. The regulatory profile of each cumulus-oocyte complex is likely associated with the oocytes' developmental potential to derive an embryo.}, } @article {pmid29747586, year = {2018}, author = {Oda, M and Wakabayashi, S and Ari Wijetunga, N and Yuasa, S and Enomoto, H and Kaneda, R and Yoon, SH and Mittal, N and Jing, Q and Suzuki, M and Greally, JM and Fukuda, K and Makino, S}, title = {Selective modulation of local linkages between active transcription and oxidative demethylation activity shapes cardiomyocyte-specific gene-body epigenetic status in mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {349}, pmid = {29747586}, issn = {1471-2164}, support = {22790730//Japan Society for the Promotion of Science/ ; 24689037//Ministry of Education, Culture, Sports, Science and Technology/ ; 25660256//Ministry of Education, Culture, Sports, Science and Technology/ ; 18K08085//Ministry of Education, Culture, Sports, Science and Technology/ ; }, mesh = {5-Methylcytosine/analogs & derivatives/metabolism ; Animals ; Cell Lineage/genetics ; *DNA Methylation ; *Demethylation ; Embryonic Stem Cells ; *Epigenesis, Genetic ; Female ; Genes, Essential ; *Genetic Linkage ; Liver/metabolism ; Male ; Mice, Inbred C57BL ; Myocytes, Cardiac/*metabolism ; *Transcription, Genetic ; }, abstract = {BACKGROUND: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs).

RESULTS: We found that most genes show a moderately negative correlation between transcript levels and gene lengths. As CM-specific genes are generally longer than other cell-type-specific genes, we hypothesized that the gene-body epigenetic features of CMs may support the transcriptional regulation of CM-specific genes. We found gene-body DNA hypomethylation in a CM-specific gene subset co-localized with rare gene-body marks, including RNA polymerase II (Pol II) and p300. Interestingly, 5-hydroxymethylcytosine (5hmC) within the gene body marked cell-type-specific genes at neonatal stages and active gene-body histone mark H3K36 trimethylation declined and overlapped with cell-type-specific gene-body DNA hypomethylation and selective Pol II/p300 accumulation in adulthood. Different combinations of gene-body epigenetic modifications were also observed with genome-wide scale cell-type specificity, revealing the occurrence of dynamic epigenetic rearrangements in GBRs across different cell types.

CONCLUSIONS: As 5hmC enrichment proceeded to hypomethylated GBRs, we considered that hypomethylation may not represent a static state but rather an equilibrium state of turnover due to the balance between local methylation linked to transcription and Tet oxidative modification causing demethylation. Accordingly, we conclude that demethylation in CMs can be a used to establish such cell-type-specific epigenetic domains in relation to liver cells. The establishment of cell-type-specific epigenetic control may also change genomic contexts of evolution and may contribute to the development of cell-type-specific transcriptional coordination.}, } @article {pmid29747585, year = {2018}, author = {Walter, RB and Boswell, M and Chang, J and Boswell, WT and Lu, Y and Navarro, K and Walter, SM and Walter, DJ and Salinas, R and Savage, M}, title = {Waveband specific transcriptional control of select genetic pathways in vertebrate skin (Xiphophorus maculatus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {355}, pmid = {29747585}, issn = {1471-2164}, support = {R24 OD011199/OD/NIH HHS/United States ; R24-OD-011120//NIH Office of the Director/ ; R24 OD011120/OD/NIH HHS/United States ; R24 OD018555/OD/NIH HHS/United States ; R24-OD-018555//National Institute of General Medical Sciences/ ; R24-OD-011199//NIH Office of the Director/ ; }, mesh = {Animals ; Cyprinodontiformes/*genetics ; Down-Regulation ; Epidermal Growth Factor/genetics ; Female ; *Fluorescence ; Gene Expression Regulation/*radiation effects ; Male ; Reproducibility of Results ; Sequence Analysis, RNA ; Skin/metabolism/*radiation effects ; Transcription, Genetic/*radiation effects ; Up-Regulation ; }, abstract = {BACKGROUND: Evolution occurred exclusively under the full spectrum of sunlight. Conscription of narrow regions of the solar spectrum by specific photoreceptors suggests a common strategy for regulation of genetic pathways. Fluorescent light (FL) does not possess the complexity of the solar spectrum and has only been in service for about 60 years. If vertebrates evolved specific genetic responses regulated by light wavelengths representing the entire solar spectrum, there may be genetic consequences to reducing the spectral complexity of light.

RESULTS: We utilized RNA-Seq to assess changes in the transcriptional profiles of Xiphophorus maculatus skin after exposure to FL ("cool white"), or narrow wavelength regions of light between 350 and 600 nm (i.e., 50 nm or 10 nm regions, herein termed "wavebands"). Exposure to each 50 nm waveband identified sets of genes representing discrete pathways that showed waveband specific transcriptional modulation. For example, 350-400 or 450-500 nm waveband exposures resulted in opposite regulation of gene sets marking necrosis and apoptosis (i.e., 350-400 nm; necrosis suppression, apoptosis activation, while 450-500 nm; apoptosis suppression, necrosis activation). Further investigation of specific transcriptional modulation employing successive 10 nm waveband exposures between 500 and 550 nm showed; (a) greater numbers of genes may be transcriptionally modulated after 10 nm exposures, than observed for 50 nm or FL exposures, (b) the 10 nm wavebands induced gene sets showing greater functional specificity than 50 nm or FL exposures, and (c) the genetic effects of FL are primarily due to 30 nm between 500 and 530 nm. Interestingly, many genetic pathways exhibited completely opposite transcriptional effects after different waveband exposures. For example, the epidermal growth factor (EGF) pathway exhibits transcriptional suppression after FL exposure, becomes highly active after 450-500 nm waveband exposure, and again, exhibits strong transcriptional suppression after exposure to the 520-530 nm waveband.

CONCLUSIONS: Collectively, these results suggest one may manipulate transcription of specific genetic pathways in skin by exposure of the intact animal to specific wavebands of light. In addition, we identify genes transcriptionally modulated in a predictable manner by specific waveband exposures. Such genes, and their regulatory elements, may represent valuable tools for genetic engineering and gene therapy protocols.}, } @article {pmid29747580, year = {2018}, author = {Ye, X and Zhong, Z and Liu, H and Lin, L and Guo, M and Guo, W and Wang, Z and Zhang, Q and Feng, L and Lu, G and Zhang, F and Chen, Q}, title = {Whole genome and transcriptome analysis reveal adaptive strategies and pathogenesis of Calonectria pseudoreteaudii to Eucalyptus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {358}, pmid = {29747580}, issn = {1471-2164}, support = {K81150002//the Project of Financial Department of Fujian Province/ ; K8112014A//the Project of Financial Department of Fujian Province/ ; K8113001A//the Project of Financial Department of Fujian Province/ ; Z150702//Jinshan College of Fujian Agriculture and Forestry university/ ; }, mesh = {Adaptation, Physiological/*genetics ; Biological Transport ; Culture Media ; Eucalyptus/*microbiology ; *Gene Expression Profiling ; Genes, Fungal ; *Genome, Fungal ; Hypocreales/genetics/pathogenicity/*physiology ; Phylogeny ; Plant Diseases/microbiology ; Plant Leaves/microbiology ; Virulence Factors ; }, abstract = {BACKGROUND: Leaf blight caused by Calonectria spp. is one of the most destructive diseases to affect Eucalyptus nurseries and plantations. These pathogens mainly attack Eucalyptus, a tree with a diversity of secondary metabolites employed as defense-related phytoalexins. To unravel the fungal adaptive mechanisms to various phytoalexins, we examined the genome of C. pseudoreteaudii, which is one of the most aggressive pathogens in southeast Asia.

RESULTS: A 63.7 Mb genome with 14,355 coding genes of C. pseudoreteaudii were assembled. Genomic comparisons identified 1785 species-specific gene families in C. pseudoreteaudii. Most of them were not annotated and those annotated genes were enriched in peptidase activity, pathogenesis, oxidoreductase activity, etc. RNA-seq showed that 4425 genes were differentially expressed on the eucalyptus(the resistant cultivar E. grandis×E.camaldulensis M1) tissue induced medium. The annotation of GO term and KEGG pathway indicated that some of the differential expression genes were involved in detoxification and transportation, such as genes encoding ABC transporters, degrading enzymes of aromatic compounds and so on.

CONCLUSIONS: Potential genomic determinants of phytoalexin detoxification were identified in C. pseudoreteaudii by comparison with 13 other fungi. This pathogen seems to employ membrane transporters and degradation enzymes to detoxify Eucalyptus phytoalexins. Remarkably, the Calonectria genome possesses a surprising number of secondary metabolism backbone enzyme genes involving toxin biosynthesis. It is also especially suited for cutin and lignin degradation. This indicates that toxin and cell wall degrading enzymes may act important roles in the establishment of Calonectria leaf blight. This study provides further understanding on the mechanism of pathogenesis in Calonectria.}, } @article {pmid29747577, year = {2018}, author = {Ren, GJ and Fan, XC and Liu, TL and Wang, SS and Zhao, GH}, title = {Genome-wide analysis of differentially expressed profiles of mRNAs, lncRNAs and circRNAs during Cryptosporidium baileyi infection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {356}, pmid = {29747577}, issn = {1471-2164}, support = {2017YFD0501305//National Key R&D Program of China/ ; 31572509//National Natural Science Foundation of China/ ; 2016NY-113//Shaanxi science and technology project/ ; 2016M592848//China Postdoctoral Science Foundation funded project/ ; None//Shaanxi Postdoctoral Science Foundation/ ; }, mesh = {Animals ; Biomarkers/metabolism ; Chickens/microbiology ; Cryptosporidiosis/genetics/*microbiology ; Cryptosporidium/*genetics ; *Gene Expression Profiling ; *Genes, Protozoan ; *Genome-Wide Association Study ; Poultry Diseases/genetics/*microbiology/therapy ; RNA/*genetics ; RNA, Long Noncoding/*genetics ; RNA, Messenger/*genetics ; Reproducibility of Results ; Sequence Analysis, RNA ; Trachea/metabolism ; }, abstract = {BACKGROUND: Cryptosporidium baileyi is the most common Cryptosporidium species in birds. However, effective prevention measures and treatment for C. baileyi infection were still not available. Long non-coding RNAs (lncRNAs) and circular RNAs (circRNAs) play important roles in regulating occurrence and progression of many diseases and are identified as effective biomarkers for diagnosis and prognosis of several diseases. In the present study, the expression profiles of host mRNAs, lncRNAs and circRNAs associated with C. baileyi infection were investigated for the first time.

RESULTS: The tracheal tissues of experimental (C. baileyi infection) and control chickens were collected for deep RNA sequencing, and 545,479,934 clean reads were obtained. Of them, 1376 novel lncRNAs were identified, including 1161 long intergenic non-coding RNAs (lincRNAs) and 215 anti-sense lncRNAs. A total of 124 lncRNAs were found to be significantly differentially expressed between the experimental and control groups. Additionally, 14,698 mRNAs and 9085 circRNAs were identified, and significantly different expressions were observed for 1317 mRNAs and 104 circRNAs between two groups. Bioinformatic analyses of gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway for their targets and source genes suggested that these dysregulated genes may be involved in the interaction between the host and C. baileyi.

CONCLUSIONS: The present study revealed the expression profiles of mRNAs, lncRNAs and circRNAs during C. baileyi infection for the first time, and sheds lights on the roles of lncRNAs and circRNAs underlying the pathogenesis of Cryptosporidium infection.}, } @article {pmid29747573, year = {2018}, author = {Pisarenko, SV and Kovalev, DA and Volynkina, AS and Ponomarenko, DG and Rusanova, DV and Zharinova, NV and Khachaturova, AA and Tokareva, LE and Khvoynova, IG and Kulichenko, AN}, title = {Global evolution and phylogeography of Brucella melitensis strains.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {353}, pmid = {29747573}, issn = {1471-2164}, mesh = {Bacterial Typing Techniques ; Bayes Theorem ; Brucella melitensis/classification/*genetics ; *Evolution, Molecular ; *Genes, Bacterial ; Genotype ; *Phylogeny ; Phylogeography ; Polymorphism, Single Nucleotide ; Species Specificity ; }, abstract = {BACKGROUND: Brucellosis is a bacterial zoonotic disease. Annually in the world more than 500,000 new cases of brucellosis in humans are registered. In this study, we propose an evolutionary model of the historical distribution of B. melitensis based on the full-genomic SNP analysis of 98 strains.

RESULTS: We performed an analysis of the SNP of the complete genomes of 98 B. melitensis strains isolated in different geographical regions of the world to obtain relevant information on the population structure, genetic diversity and the evolution history of the species. Using genomic sequences of 21 strains of B. melitensis isolated in Russia and WGS data from the NCBI database, it was possible to identify five main genotypes and 13 species genotypes for analysis. Data analysis based on the Bayesian Phylogenetics and Phylogeography method allowed to determine the regions of geographical origin and the expected pathways of distribution of the main lines (genotypes and subgenotypes) of the pathogen.

CONCLUSIONS: Within the framework of our study, the model of global evolution and phylogeography of B. melitensis strains isolated in various regions of the planet was proposed for the first time. The sets of unique specific SNPs described in our study, for all identified genotypes and subgenotypes, can be used to develop new bacterial typing and identification systems for B. melitensis.}, } @article {pmid29747572, year = {2018}, author = {Qian, L and Wang, H and Yan, J and Pan, T and Jiang, S and Rao, D and Zhang, B}, title = {Multiple independent structural dynamic events in the evolution of snake mitochondrial genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {354}, pmid = {29747572}, issn = {1471-2164}, support = {yqh100087//Graduate Student Academic Innovation Research Project of Anhui University/ ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Rearrangement ; *Genome, Mitochondrial ; Likelihood Functions ; Phylogeny ; Snakes/classification/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: Mitochondrial DNA sequences have long been used in phylogenetic studies. However, little attention has been paid to the changes in gene arrangement patterns in the snake's mitogenome. Here, we analyzed the complete mitogenome sequences and structures of 65 snake species from 14 families and examined their structural patterns, organization and evolution. Our purpose was to further investigate the evolutionary implications and possible rearrangement mechanisms of the mitogenome within snakes.

RESULTS: In total, eleven types of mitochondrial gene arrangement patterns were detected (Type I, II, III, III-A, III-B, III-B1, III-C, III-D, III-E, III-F, III-G), with mitochondrial genome rearrangements being a major trend in snakes, especially in Alethinophidia. In snake mitogenomes, the rearrangements mainly involved three processes, gene loss, translocation and duplication. Within Scolecophidia, the OL was lost several times in Typhlopidae and Leptotyphlopidae, but persisted as a plesiomorphy in the Alethinophidia. Duplication of the control region and translocation of the tRNALeu gene are two visible features in Alethinophidian mitochondrial genomes. Independently and stochastically, the duplication of pseudo-Pro (P*) emerged in seven different lineages of unequal size in three families, indicating that the presence of P* was a polytopic event in the mitogenome.

CONCLUSIONS: The WANCY tRNA gene cluster and the control regions and their adjacent segments were hotspots for mitogenome rearrangement. Maintenance of duplicate control regions may be the source for snake mitogenome structural diversity.}, } @article {pmid29747567, year = {2018}, author = {Banerjee, N and Polushina, T and Bettella, F and Giddaluru, S and Steen, VM and Andreassen, OA and Le Hellard, S}, title = {Recently evolved human-specific methylated regions are enriched in schizophrenia signals.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {63}, pmid = {29747567}, issn = {1471-2148}, support = {#2 T23273//Norges Forskningsråd/International ; SKGJ-MED-008//KG Jebsen Foundation/International ; }, mesh = {Adult ; Bipolar Disorder/genetics ; Body Height/genetics ; Body Mass Index ; DNA Methylation/*genetics ; *Evolution, Molecular ; Female ; Genetic Markers ; Genome-Wide Association Study ; Genotype ; Humans ; Major Histocompatibility Complex/genetics ; Male ; Molecular Sequence Annotation ; Multifactorial Inheritance ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Schizophrenia/*genetics ; }, abstract = {BACKGROUND: One explanation for the persistence of schizophrenia despite the reduced fertility of patients is that it is a by-product of recent human evolution. This hypothesis is supported by evidence suggesting that recently-evolved genomic regions in humans are involved in the genetic risk for schizophrenia. Using summary statistics from genome-wide association studies (GWAS) of schizophrenia and 11 other phenotypes, we tested for enrichment of association with GWAS traits in regions that have undergone methylation changes in the human lineage compared to Neanderthals and Denisovans, i.e. human-specific differentially methylated regions (DMRs). We used analytical tools that evaluate polygenic enrichment of a subset of genomic variants against all variants.

RESULTS: Schizophrenia was the only trait in which DMR SNPs showed clear enrichment of association that passed the genome-wide significance threshold. The enrichment was not observed for Neanderthal or Denisovan DMRs. The enrichment seen in human DMRs is comparable to that for genomic regions tagged by Neanderthal Selective Sweep markers, and stronger than that for Human Accelerated Regions. The enrichment survives multiple testing performed through permutation (n = 10,000) and bootstrapping (n = 5000) in INRICH (p < 0.01). Some enrichment of association with height was observed at the gene level.

CONCLUSIONS: Regions where DNA methylation modifications have changed during recent human evolution show enrichment of association with schizophrenia and possibly with height. Our study further supports the hypothesis that genetic variants conferring risk of schizophrenia co-occur in genomic regions that have changed as the human species evolved. Since methylation is an epigenetic mark, potentially mediated by environmental changes, our results also suggest that interaction with the environment might have contributed to that association.}, } @article {pmid29747566, year = {2018}, author = {Oetjens, MT and Martin, A and Veeramah, KR and Kidd, JM}, title = {Analysis of the canid Y-chromosome phylogeny using short-read sequencing data reveals the presence of distinct haplogroups among Neolithic European dogs.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {350}, pmid = {29747566}, issn = {1471-2164}, support = {R01 GM103961/GM/NIGMS NIH HHS/United States ; R01GM103961//National Institute of General Medical Sciences/ ; }, mesh = {Animals ; Coyotes/classification/*genetics ; DNA, Mitochondrial/genetics ; Dogs/classification/*genetics ; *Evolution, Molecular ; Genetic Variation ; Genome ; *Haplotypes ; Male ; *Phylogeny ; Sequence Analysis, DNA/*methods ; Wolves/classification/*genetics ; *Y Chromosome ; }, abstract = {BACKGROUND: Most genetic analyses of ancient and modern dogs have focused on variation in the autosomes or on the mitochondria. Mitochondrial DNA is more easily obtained from ancient samples than nuclear DNA and mitochondrial analyses have revealed important insights into the evolutionary history of canids. Utilizing a recently published dog Y-chromosome reference, we analyzed Y-chromosome sequence across a diverse collection of canids and determined the Y haplogroup of three ancient European dogs.

RESULTS: We identified 1121 biallelic Y-chromosome SNVs using whole-genome sequences from 118 canids and defined variants diagnostic to distinct dog Y haplogroups. Similar to that of the mitochondria and previous more limited studies of Y diversity, we observe several deep splits in the Y-chromosome tree which may be the result of retained Y-chromosome diversity which predates dog domestication or post-domestication admixture with wolves. We find that Y-chromosomes from three ancient European dogs (4700-7000 years old) belong to distinct clades.

CONCLUSIONS: We estimate that the time to the most recent comment ancestor of dog Y haplogroups is 68-151 thousand years ago. Analysis of three Y-chromosomes from the Neolithic confirms long stranding population structure among European dogs.}, } @article {pmid29747009, year = {2018}, author = {Toussaint, EFA and Short, AEZ}, title = {Transoceanic Stepping-stones between Cretaceous waterfalls? The enigmatic biogeography of pantropical Oocyclus cascade beetles.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {416-428}, doi = {10.1016/j.ympev.2018.04.023}, pmid = {29747009}, issn = {1095-9513}, abstract = {Beetles have colonized freshwater habitats multiple times throughout their evolutionary history. Some of these aquatic lineages are associated exclusively with waterfall-like habitats, often with modified morphologies to cope with their unusual way of life. The historical biogeography of such cascade beetle lineages has been shown to strongly reflect ancient tectonic events. We focus on the pantropical genus Oocyclus of which species dwell in waterfalls and associated habitats. We infer the first molecular phylogeny of Oocyclus using a dataset of seven gene fragments. We recover a well resolved phylogenetic hypothesis, with a monophyletic Oocyclus divided in three genetically well-differentiated subclades which correspond to geography. Comparative dating analyses across Hydrophilidae based on ten fossil calibrations recover a Cretaceous origin for the genus. Based on a comprehensive suite of ancestral range analyses, we suggest a unique pattern with an origin in Southeast Asia followed by the successive colonization of India and the Neotropics via transoceanic stepping-stone dispersal. Diversification rate analyses support a scenario in which old Oocyclus lineages diversified slowly with a homogeneous rate regime. Waterfall beetle radiations are ancient and remarkably track Earth's paleogeological history, shedding light on intricate patterns of macroevolution.}, } @article {pmid29746729, year = {2018}, author = {Weir, JC}, title = {The evolution of colour polymorphism in British winter-active Lepidoptera in response to search image use by avian predators.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {8}, pages = {1109-1126}, doi = {10.1111/jeb.13290}, pmid = {29746729}, issn = {1420-9101}, abstract = {Phenotypic polymorphism in cryptic species is widespread. This may evolve in response to search image use by predators exerting negative frequency-dependent selection on intraspecific colour morphs, 'apostatic selection'. Evidence exists to indicate search image formation by predators and apostatic selection operating on wild prey populations, though not to demonstrate search image use directly resulting in apostatic selection. The present study attempted to address this deficiency, using British Lepidoptera active in winter as a model system. It has been proposed that the typically polymorphic wing colouration of these species represents an anti-search image adaptation against birds. To test (a) for search image-driven apostatic selection, dimorphic populations of artificial moth-like models were established in woodland at varying relative morph frequencies and exposed to predation by natural populations of birds. In addition, to test (b) whether abundance and degree of polymorphism are correlated across British winter-active moths, as predicted where search image use drives apostatic selection, a series of phylogenetic comparative analyses were conducted. There was a positive relationship between artificial morph frequency and probability of predation, consistent with birds utilizing search images and exerting apostatic selection. Abundance and degree of polymorphism were found to be positively correlated across British Lepidoptera active in winter, though not across all taxonomic groups analysed. This evidence is consistent with polymorphism in this group having evolved in response to search image-driven apostatic selection and supports the viability of this mechanism as a means by which phenotypic and genetic variation may be maintained in natural populations.}, } @article {pmid29746704, year = {2018}, author = {Sánchez-Guillén, RA and Cordero-Rivera, A and Rivas-Torres, A and Wellenreuther, M and Bybee, S and Hansson, B and Velasquez-Vélez, MI and Realpe, E and Chávez-Ríos, JR and Villalobos, F and Dumont, H}, title = {The evolutionary history of colour polymorphism in Ischnura damselflies.}, journal = {Journal of evolutionary biology}, volume = {}, number = {}, pages = {}, doi = {10.1111/jeb.13289}, pmid = {29746704}, issn = {1420-9101}, abstract = {A major challenge in evolutionary biology consists of understanding how genetic and phenotypic variation is created and maintained. In this study, we investigated the origin(s) and evolutionary patterns of the female-limited colour polymorphism in ischnuran damselflies. These consist of the presence of one to three colour morphs: one androchrome morph with a coloration that is similar to the male and two gynochrome morphs (infuscans and aurantiaca) with female-specific coloration. We (i) documented the colour and mating system of 44 of the 75 taxa within the genus Ischnura, (ii) reconstructed the evolutionary history of colour and mating system to identify the ancestral state, (iii) evaluated the stability of the colour morph status over time and (iv) tested for a correlation between colour and mating system. We found that the ancestral female colour of Ischnura was monomorphic and aurantiaca and that colour morph status changed over time, characterized by many gains and losses across the species tree. Our results further showed that colour polymorphism is significantly more frequent among polyandric species, whereas monandric species tend to be monomorphic. Research on some Ischnura species has shown that colour morphs have evolved to reduce male mating harassment, and our finding that the same phenotypic morphs have evolved multiple times (convergent evolution) suggests that several species in this genus might be experiencing similar selective pressures.}, } @article {pmid29746697, year = {2018}, author = {Legras, JL and Galeote, V and Bigey, F and Camarasa, C and Marsit, S and Nidelet, T and Sanchez, I and Couloux, A and Guy, J and Franco-Duarte, R and Marcet-Houben, M and Gabaldon, T and Schuller, D and Sampaio, JP and Dequin, S}, title = {Adaptation of S. cerevisiae to Fermented Food Environments Reveals Remarkable Genome Plasticity and the Footprints of Domestication.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1712-1727}, pmid = {29746697}, issn = {1537-1719}, abstract = {The budding yeast Saccharomyces cerevisiae can be found in the wild and is also frequently associated with human activities. Despite recent insights into the phylogeny of this species, much is still unknown about how evolutionary processes related to anthropogenic niches have shaped the genomes and phenotypes of S. cerevisiae. To address this question, we performed population-level sequencing of 82 S. cerevisiae strains from wine, flor, rum, dairy products, bakeries, and the natural environment (oak trees). These genomic data enabled us to delineate specific genetic groups corresponding to the different ecological niches and revealed high genome content variation across the groups. Most of these strains, compared with the reference genome, possessed additional genetic elements acquired by introgression or horizontal transfer, several of which were population-specific. In addition, several genomic regions in each population showed evidence of nonneutral evolution, as shown by high differentiation, or of selective sweeps including genes with key functions in these environments (e.g., amino acid transport for wine yeast). Linking genetics to lifestyle differences and metabolite traits has enabled us to elucidate the genetic basis of several niche-specific population traits, such as growth on galactose for cheese strains. These data indicate that yeast has been subjected to various divergent selective pressures depending on its niche, requiring the development of customized genomes for better survival in these environments. These striking genome dynamics associated with local adaptation and domestication reveal the remarkable plasticity of the S. cerevisiae genome, revealing this species to be an amazing complex of specialized populations.}, } @article {pmid29745868, year = {2018}, author = {Sakamoto, M and Iino, T and Yuki, M and Ohkuma, M}, title = {Lawsonibacter asaccharolyticus gen. nov., sp. nov., a butyrate-producing bacterium isolated from human faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2074-2081}, doi = {10.1099/ijsem.0.002800}, pmid = {29745868}, issn = {1466-5034}, mesh = {Adult ; Bacterial Typing Techniques ; Base Composition ; Butyrates/*metabolism ; Clostridiales/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Feces/*microbiology ; Female ; Humans ; Japan ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {An obligately anaerobic, Gram-positive, non-spore-forming, straight rod-shaped bacterium, designated strain 3BBH22T, was isolated from a faecal sample of a healthy Japanese woman. The 16S rRNA gene sequence analysis showed that strain 3BBH22T formed a monophyletic cluster with species in the genera Pseudoflavonifractor and Flavonifractor within the family Ruminococcaceae and had highest similarity to Pseudoflavonifractor capillosus ATCC 29799T (96.7 % sequence similarity), followed by Flavonifractor plautii ATCC 29863T (96.4 %). Acetate and butyrate were produced by strain 3BBH22T as metabolic end-products. The major cellular fatty acids were C14 : 0, C16 : 0, C18 : 1ω9c, C16 : 0 dimethyl acetal, C18 : 0 and C18 : 2ω6,9c. No respiratory quinones were detected. In contrast to F. plautii JCM 32125T, strain 3BBH22T did not degrade quercetin, one of the flavonoids. P. capillosus JCM 32126T also did not. Strain 3BBH22T was differentiated from P. capillosus JCM 32126T by its inability to hydrolyse aesculin. The G+C content of the genomic DNA was 61.2±1.0 mol%. On the basis of these data and the phylogenetic tree based on 89 proteins, strain 3BBH22T represents a novel species in a novel genus of the family Ruminococcaceae, for which the name Lawsonibacter asaccharolyticus gen. nov., sp. nov. is proposed. The type strain of L. asaccharolyticus is 3BBH22T (=JCM 32166T=DSM 106493T).}, } @article {pmid29745867, year = {2018}, author = {Kanjanasuntree, R and Kim, JH and Yoon, JH and Sukhoom, A and Kantachote, D and Kim, W}, title = {Arenimonas halophila sp. nov., isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2188-2193}, doi = {10.1099/ijsem.0.002801}, pmid = {29745867}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; Xanthomonadaceae/*classification/genetics/isolation & purification ; }, abstract = {A Gram-staining-negative, aerobic, non-motile, rod-shaped bacterium, designated CAU 1453T, was isolated from soil and its taxonomic position was investigated using a polyphasic approach. Strain CAU 1453T grew optimally at 30 °C and at pH 6.5 in the presence of 1 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that CAU 1453T represented a member of the genus Arenimonas and was most closely related to Arenimonas donghaensis KACC 11381T (97.2 % similarity). CAU 1453T contained ubiquinone-8 (Q-8) as the predominant isoprenoid quinone and iso-C15 : 0 and iso-C16 : 0 as the major cellular fatty acids. The polar lipids consisted of diphosphatidylglycerol, a phosphoglycolipid, an aminophospholipid, two unidentified phospholipids and two unidentified glycolipids. CAU 1453T showed low DNA-DNA relatedness with the most closely related strain, A. donghaensis KACC 11381T (26.5 %). The DNA G+C content was 67.3 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, CAU 1453T represents a novel species of the genus Arenimonas, for which the name Arenimonas halophila sp. nov. is proposed. The type strain is CAU 1453T (=KCTC 62235T=NBRC 113093T).}, } @article {pmid29745866, year = {2018}, author = {Zhang, C and Rabiee, M and Sayyari, E and Mirarab, S}, title = {ASTRAL-III: polynomial time species tree reconstruction from partially resolved gene trees.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 6}, pages = {153}, pmid = {29745866}, issn = {1471-2105}, abstract = {BACKGROUND: Evolutionary histories can be discordant across the genome, and such discordances need to be considered in reconstructing the species phylogeny. ASTRAL is one of the leading methods for inferring species trees from gene trees while accounting for gene tree discordance. ASTRAL uses dynamic programming to search for the tree that shares the maximum number of quartet topologies with input gene trees, restricting itself to a predefined set of bipartitions.

RESULTS: We introduce ASTRAL-III, which substantially improves the running time of ASTRAL-II and guarantees polynomial running time as a function of both the number of species (n) and the number of genes (k). ASTRAL-III limits the bipartition constraint set (X) to grow at most linearly with n and k. Moreover, it handles polytomies more efficiently than ASTRAL-II, exploits similarities between gene trees better, and uses several techniques to avoid searching parts of the search space that are mathematically guaranteed not to include the optimal tree. The asymptotic running time of ASTRAL-III in the presence of polytomies is [Formula: see text] where D=O(nk) is the sum of degrees of all unique nodes in input trees. The running time improvements enable us to test whether contracting low support branches in gene trees improves the accuracy by reducing noise. In extensive simulations, we show that removing branches with very low support (e.g., below 10%) improves accuracy while overly aggressive filtering is harmful. We observe on a biological avian phylogenomic dataset of 14K genes that contracting low support branches greatly improve results.

CONCLUSIONS: ASTRAL-III is a faster version of the ASTRAL method for phylogenetic reconstruction and can scale up to 10,000 species. With ASTRAL-III, low support branches can be removed, resulting in improved accuracy.}, } @article {pmid29745865, year = {2018}, author = {Chindelevitch, L and Pereira Zanetti, JP and Meidanis, J}, title = {On the rank-distance median of 3 permutations.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 6}, pages = {142}, pmid = {29745865}, issn = {1471-2105}, support = {//CIHR/Canada ; }, abstract = {BACKGROUND: Recently, Pereira Zanetti, Biller and Meidanis have proposed a new definition of a rearrangement distance between genomes. In this formulation, each genome is represented as a matrix, and the distance d is the rank distance between these matrices. Although defined in terms of matrices, the rank distance is equal to the minimum total weight of a series of weighted operations that leads from one genome to the other, including inversions, translocations, transpositions, and others. The computational complexity of the median-of-three problem according to this distance is currently unknown. The genome matrices are a special kind of permutation matrices, which we study in this paper. In their paper, the authors provide an [Formula: see text] algorithm for determining three candidate medians, prove the tight approximation ratio [Formula: see text], and provide a sufficient condition for their candidates to be true medians. They also conduct some experiments that suggest that their method is accurate on simulated and real data.

RESULTS: In this paper, we extend their results and provide the following: Three invariants characterizing the problem of finding the median of 3 matrices A sufficient condition for uniqueness of medians that can be checked in O(n) A faster, [Formula: see text] algorithm for determining the median under this condition A new heuristic algorithm for this problem based on compressed sensing A [Formula: see text] algorithm that exactly solves the problem when the inputs are orthogonal matrices, a class that includes both permutations and genomes as special cases.

CONCLUSIONS: Our work provides the first proof that, with respect to the rank distance, the problem of finding the median of 3 genomes, as well as the median of 3 permutations, is exactly solvable in polynomial time, a result which should be contrasted with its NP-hardness for the DCJ (double cut-and-join) distance and most other families of genome rearrangement operations. This result, backed by our experimental tests, indicates that the rank distance is a viable alternative to the DCJ distance widely used in genome comparisons.}, } @article {pmid29745863, year = {2018}, author = {Goz, E and Tsalenchuck, Y and Benaroya, RO and Zafrir, Z and Atar, S and Altman, T and Julander, J and Tuller, T}, title = {Generation and comparative genomics of synthetic dengue viruses.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 6}, pages = {140}, pmid = {29745863}, issn = {1471-2105}, abstract = {BACKGROUND: Synthetic virology is an important multidisciplinary scientific field, with emerging applications in biotechnology and medicine, aiming at developing methods to generate and engineer synthetic viruses. In particular, many of the RNA viruses, including among others the Dengue and Zika, are widespread pathogens of significant importance to human health. The ability to design and synthesize such viruses may contribute to exploring novel approaches for developing vaccines and virus based therapies.

RESULTS: Here we develop a full multidisciplinary pipeline for generation and analysis of synthetic RNA viruses and specifically apply it to Dengue virus serotype 2 (DENV-2). The major steps of the pipeline include comparative genomics of endogenous and synthetic viral strains. Specifically, we show that although the synthetic DENV-2 viruses were found to have lower nucleotide variability, their phenotype, as reflected in the study of the AG129 mouse model morbidity, RNA levels, and neutralization antibodies, is similar or even more pathogenic in comparison to the wildtype master strain. Additionally, the highly variable positions, identified in the analyzed DENV-2 population, were found to overlap with less conserved homologous positions in Zika virus and other Dengue serotypes. These results may suggest that synthetic DENV-2 could enhance virulence if the correct sequence is selected.

CONCLUSIONS: The approach reported in this study can be used to generate and analyze synthetic RNA viruses both on genotypic and on phenotypic level. It could be applied for understanding the functionality and the fitness effects of any set of mutations in viral RNA and for editing RNA viruses for various target applications.}, } @article {pmid29745861, year = {2018}, author = {Rubert, DP and Hoshino, EA and Braga, MDV and Stoye, J and Martinez, FV}, title = {Computing the family-free DCJ similarity.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 6}, pages = {152}, pmid = {29745861}, issn = {1471-2105}, abstract = {BACKGROUND: The genomic similarity is a large-scale measure for comparing two given genomes. In this work we study the (NP-hard) problem of computing the genomic similarity under the DCJ model in a setting that does not assume that the genes of the compared genomes are grouped into gene families. This problem is called family-free DCJ similarity.

RESULTS: We propose an exact ILP algorithm to solve the family-free DCJ similarity problem, then we show its APX-hardness and present four combinatorial heuristics with computational experiments comparing their results to the ILP.

CONCLUSIONS: We show that the family-free DCJ similarity can be computed in reasonable time, although for larger genomes it is necessary to resort to heuristics. This provides a basis for further studies on the applicability and model refinement of family-free whole genome similarity measures.}, } @article {pmid29745860, year = {2018}, author = {Liu, F and Chen, S and Heiner, M and Song, H}, title = {Modeling biological systems with uncertain kinetic data using fuzzy continuous Petri nets.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {42}, pmid = {29745860}, issn = {1752-0509}, abstract = {BACKGROUND: Uncertainties exist in many biological systems, which can be classified as random uncertainties and fuzzy uncertainties. The former can usually be dealt with using stochastic methods, while the latter have to be handled with such approaches as fuzzy methods.

RESULTS: In this paper, we focus on a special type of biological systems that can be described using ordinary differential equations or continuous Petri nets (CPNs), but some kinetic parameters are missing or inaccurate. For this, we propose a class of fuzzy continuous Petri nets (FCPNs) by combining CPNs and fuzzy logics. We also present and implement a simulation algorithm for FCPNs, and illustrate our method with the heat shock response system.

CONCLUSIONS: This approach can be used to model biological systems where some kinetic parameters are not available or their values vary due to some environmental factors.}, } @article {pmid29745859, year = {2018}, author = {Zhang, Z and Song, J and Tang, J and Xu, X and Guo, F}, title = {Detecting complexes from edge-weighted PPI networks via genes expression analysis.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {40}, pmid = {29745859}, issn = {1752-0509}, abstract = {BACKGROUND: Identifying complexes from PPI networks has become a key problem to elucidate protein functions and identify signal and biological processes in a cell. Proteins binding as complexes are important roles of life activity. Accurate determination of complexes in PPI networks is crucial for understanding principles of cellular organization.

RESULTS: We propose a novel method to identify complexes on PPI networks, based on different co-expression information. First, we use Markov Cluster Algorithm with an edge-weighting scheme to calculate complexes on PPI networks. Then, we propose some significant features, such as graph information and gene expression analysis, to filter and modify complexes predicted by Markov Cluster Algorithm. To evaluate our method, we test on two experimental yeast PPI networks.

CONCLUSIONS: On DIP network, our method has Precision and F-Measure values of 0.6004 and 0.5528. On MIPS network, our method has F-Measure and S n values of 0.3774 and 0.3453. Comparing to existing methods, our method improves Precision value by at least 0.1752, F-Measure value by at least 0.0448, S n value by at least 0.0771. Experiments show that our method achieves better results than some state-of-the-art methods for identifying complexes on PPI networks, with the prediction quality improved in terms of evaluation criteria.}, } @article {pmid29745858, year = {2018}, author = {Hu, J and Gao, Y and Zheng, Y and Shang, X}, title = {KF-finder: identification of key factors from host-microbial networks in cervical cancer.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {54}, pmid = {29745858}, issn = {1752-0509}, abstract = {BACKGROUND: The human body is colonized by a vast number of microbes. Microbiota can benefit many normal life processes, but can also cause many diseases by interfering the regular metabolism and immune system. Recent studies have demonstrated that the microbial community is closely associated with various types of cell carcinoma. The search for key factors, which also refer to cancer causing agents, can provide an important clue in understanding the regulatory mechanism of microbiota in uterine cervix cancer.

RESULTS: In this paper, we investigated microbiota composition and gene expression data for 58 squamous and adenosquamous cell carcinoma. A host-microbial covariance network was constructed based on the 16s rRNA and gene expression data of the samples, which consists of 259 abundant microbes and 738 differentially expressed genes (DEGs). To search for risk factors from host-microbial networks, the method of bi-partite betweenness centrality (BpBC) was used to measure the risk of a given node to a certain biological process in hosts. A web-based tool KF-finder was developed, which can efficiently query and visualize the knowledge of microbiota and differentially expressed genes (DEGs) in the network.

CONCLUSIONS: Our results suggest that prevotellaceade, tissierellaceae and fusobacteriaceae are the most abundant microbes in cervical carcinoma, and the microbial community in cervical cancer is less diverse than that of any other boy sites in health. A set of key risk factors anaerococcus, hydrogenophilaceae, eubacterium, PSMB10, KCNIP1 and KRT13 have been identified, which are thought to be involved in the regulation of viral response, cell cycle and epithelial cell differentiation in cervical cancer. It can be concluded that permanent changes of microbiota composition could be a major force for chromosomal instability, which subsequently enables the effect of key risk factors in cancer. All our results described in this paper can be freely accessed from our website at http://www.nwpu-bioinformatics.com/KF-finder/ .}, } @article {pmid29745857, year = {2018}, author = {Khan, A and Ali, A and Junaid, M and Liu, C and Kaushik, AC and Cho, WCS and Wei, DQ}, title = {Identification of novel drug targets for diamond-blackfan anemia based on RPS19 gene mutation using protein-protein interaction network.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {39}, pmid = {29745857}, issn = {1752-0509}, abstract = {BACKGROUND: Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy. In order to explore the molecular mechanisms of wild and mutated samples from DBA patients were exposed to bioinformatics investigation. Biological network of differentially expressed genes was constructed. This study aimed to identify novel therapeutic signatures in DBA and uncovered their mechanisms. The gene expression dataset of GSE14335 was used, which consists of 6 normal and 4 diseased cases. The gene ontology (GO), as well as Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed, and then protein-protein interaction (PPI) network of the identified differentially expressed genes (DEGs) was constructed by Cytoscape software.

RESULTS: A total of 607 DEGs were identified in DBA, including 433 upregulated genes and 174 downregulated genes. GO analysis results showed that upregulated DEGs were significantly enriched in biological processes, negative regulation of transcription from RNA polymerase II promoter, chemotaxis, inflammatory response, immune response, positive regulation of cell proliferation, negative regulation of cell proliferation, response to mechanical stimulus, positive regulation of cell migration, response to lipopolysaccharide, and defence response. KEGG pathway analysis revealed the TNF signalling pathway, Osteoclast differentiation, Chemokine signalling pathway, Cytokine -cytokine receptor interaction, Rheumatoid arthritis, Biosynthesis of amino acids, Biosynthesis of antibiotics and Glycine, serine and threonine metabolism. The top 10 hub genes, AKT1, IL6, NFKB1, STAT3, STAT1, RAC1, EGR1, IL8, RELA, RAC3, mTOR and CCR2 were identified from the PPI network and sub-networks.

CONCLUSION: The present study flagged that the identified DEGs and hub genes enrich our understanding of the molecular mechanisms underlying the development of DBA, and might shine some lights on identifying molecular targets and diagnostic biomarkers for DBA.}, } @article {pmid29745856, year = {2018}, author = {He, W and Jia, C and Duan, Y and Zou, Q}, title = {70ProPred: a predictor for discovering sigma70 promoters based on combining multiple features.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {44}, pmid = {29745856}, issn = {1752-0509}, abstract = {BACKGROUND: Promoter is an important sequence regulation element, which is in charge of gene transcription initiation. In prokaryotes, σ70 promoters regulate the transcription of most genes. The promoter recognition has been a crucial part of gene structure recognition. It's also the core issue of constructing gene transcriptional regulation network. With the successfully completion of genome sequencing from an increasing number of microbe species, the accurate identification of σ70 promoter regions in DNA sequence is not easy.

RESULTS: In order to improve the prediction accuracy of sigma70 promoters in prokaryote, a promoter recognition model 70ProPred was established. In this work, two sequence-based features, including position-specific trinucleotide propensity based on single-stranded characteristic (PSTNPss) and electron-ion potential values for trinucleotides (PseEIIP), were assessed to build the best prediction model. It was found that 79 features of PSTNPSS combined with 64 features of PseEIIP obtained the best performance for sigma70 promoter identification, with a promising accuracy and the Matthews correlation coefficient (MCC) at 95.56% and 0.90, respectively.

CONCLUSION: The jackknife tests showed that 70ProPred outperforms the existing sigma70 promoter prediction approaches in terms of accuracy and stability. Additionally, this approach can also be extended to predict promoters of other species. In order to facilitate experimental biologists, an online web server for the proposed method was established, which is freely available at http://server.malab.cn/70ProPred/ .}, } @article {pmid29745854, year = {2018}, author = {Nute, M and Chou, J and Molloy, EK and Warnow, T}, title = {The performance of coalescent-based species tree estimation methods under models of missing data.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 5}, pages = {286}, pmid = {29745854}, issn = {1471-2164}, mesh = {Algorithms ; Classification/*methods ; Computer Simulation ; Genes ; *Genetic Speciation ; Genomics ; *Models, Genetic ; *Phylogeny ; Species Specificity ; }, abstract = {BACKGROUND: Estimation of species trees from multiple genes is complicated by processes such as incomplete lineage sorting, gene duplication and loss, and horizontal gene transfer, that result in gene trees that differ from each other and from the species phylogeny. Methods to estimate species trees in the presence of gene tree discord due to incomplete lineage sorting have been developed and proved to be statistically consistent when gene tree discord is due only to incomplete lineage sorting and every gene tree includes the full set of species.

RESULTS: We establish statistical consistency of certain coalescent-based species tree estimation methods under some models of taxon deletion from genes. We also evaluate the impact of missing data on four species tree estimation methods (ASTRAL-II, ASTRID, MP-EST, and SVDquartets) using simulated datasets with varying levels of incomplete lineage sorting, gene tree estimation error, and degrees/patterns of missing data.

CONCLUSIONS: All the species tree estimation methods improved in accuracy as the number of genes increased and often produced highly accurate species trees even when the amount of missing data was large. These results together indicate that accurate species tree estimation is possible under a variety of conditions, even when there are substantial amounts of missing data.}, } @article {pmid29745853, year = {2018}, author = {Gong, X and Jiang, J and Duan, Z and Lu, H}, title = {A new method to measure the semantic similarity from query phenotypic abnormalities to diseases based on the human phenotype ontology.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {162}, pmid = {29745853}, issn = {1471-2105}, abstract = {BACKGROUND: Although rapid developed sequencing technologies make it possible for genotype data to be used in clinical diagnosis, it is still challenging for clinicians to understand the results of sequencing and make correct judgement based on them. Before this, diagnosis based on clinical features held a leading position. With the establishment of the Human Phenotype Ontology (HPO) and the enrichment of phenotype-disease annotations, there throws much more attention to the improvement of phenotype-based diagnosis.

RESULTS: In this study, we presented a novel method called RelativeBestPair to measure similarity from the query terms to hereditary diseases based on HPO and then rank the candidate diseases. To evaluate the performance, we simulated a set of patients based on 44 complex diseases. Besides, by adding noise or imprecision or both, cases closer to real clinical conditions were generated. Thus, four simulated datasets were used to make comparison among RelativeBestPair and seven existing semantic similarity measures. RelativeBestPair ranked the underlying disease as top 1 on 93.73% of the simulated dataset without noise and imprecision, 93.64% of the simulated dataset with noise and without imprecision, 39.82% of the simulated dataset without noise and with imprecision, and 33.64% of the simulated dataset with both noise and imprecision.

CONCLUSION: Compared with the seven existing semantic similarity measures, RelativeBestPair showed similar performance in two datasets without imprecision. While RelativeBestPair appeared to be equal to Resnik and better than other six methods in the simulated dataset without noise and with imprecision, it significantly outperformed all other seven methods in the simulated dataset with both noise and imprecision. It can be indicated that RelativeBestPair might be of great help in clinical setting.}, } @article {pmid29745852, year = {2018}, author = {Shen, F and Wu, X and Shi, L and Zhang, H and Chen, Y and Qi, X and Wang, Z and Li, X}, title = {Transcriptomic and metabolic flux analyses reveal shift of metabolic patterns during rice grain development.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {47}, pmid = {29745852}, issn = {1752-0509}, abstract = {BACKGROUND: Rice (Oryza sativa) is one of the most important grain crops, which serves as food source for nearly half of the world population. The study of rice development process as well as related strategies for production has made significant progress. However, the comprehensive study on development of different rice tissues at both transcriptomic and metabolic flux level across different stages was lacked.

RESULTS: In this study, we performed RNA-Seq and characterized the expression profiles of differentiated tissues from Oryza sativa Zhonghua 11, including leaves, sheath, stamen, pistil, lemma and palea of the booting stage, and embryo, endosperm, lemma and palea of the mature grain stage. By integrating this set of transcriptome data of different rice tissues at different stages with a genome-scale rice metabolic model, we generated tissue-specific models and investigated the shift of metabolic patterns, and the discrepancy between transcriptomic and metabolic level. We found although the flux patterns are not very similar with the gene expression pattern, the tissues at booting stage and mature grain stage can be separately clustered by primary metabolism at either level. While the gene expression and flux distribution of secondary metabolism is more diverse across tissues and stages. The critical rate-limiting reactions and pathways were also identified. In addition, we compared the patterns of the same tissue at different stages and the different tissues at same stage. There are more altered pathways at gene expression level than metabolic level, which indicate the metabolism is more robust to reflect the phenotype, and might largely because of the complex post-transcriptional modification.

CONCLUSIONS: The tissue-specific models revealed more detail metabolic pattern shift among different tissues and stages, which is of great significance to uncover mechanism of rice grain development and further improve production and quality of rice.}, } @article {pmid29745851, year = {2018}, author = {Vachaspati, P and Warnow, T}, title = {SIESTA: enhancing searches for optimal supertrees and species trees.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 5}, pages = {252}, pmid = {29745851}, issn = {1471-2164}, mesh = {*Algorithms ; Animals ; Computational Biology/methods ; *Computer Simulation ; Humans ; *Phylogeny ; *Software ; }, abstract = {BACKGROUND: Many supertree estimation and multi-locus species tree estimation methods compute trees by combining trees on subsets of the species set based on some NP-hard optimization criterion. A recent approach to computing large trees has been to constrain the search space by defining a set of "allowed bipartitions", and then use dynamic programming to find provably optimal solutions in polynomial time. Several phylogenomic estimation methods, such as ASTRAL, the MDC algorithm in PhyloNet, FastRFS, and ALE, use this approach.

RESULTS: We present SIESTA, a method that can be combined with these dynamic programming algorithms to return a data structure that compactly represents all the optimal trees in the search space. As a result, SIESTA provides multiple capabilities, including: (1) counting the number of optimal trees, (2) calculating consensus trees, (3) generating a random optimal tree, and (4) annotating branches in a given optimal tree by the proportion of optimal trees it appears in.

CONCLUSIONS: SIESTA improves the accuracy of FastRFS and ASTRAL, and is a general technique for enhancing dynamic programming methods for constrained optimization.}, } @article {pmid29745850, year = {2018}, author = {Jiao, J and Luo, M and Wang, R}, title = {Feedback regulation in a stem cell model with acute myeloid leukaemia.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {43}, pmid = {29745850}, issn = {1752-0509}, abstract = {BACKGROUND: The haematopoietic lineages with leukaemia lineages are considered in this paper. In particular, we mainly consider that haematopoietic lineages are tightly controlled by negative feedback inhibition of end-product. Actually, leukemia has been found 100 years ago. Up to now, the exact mechanism is still unknown, and many factors are thought to be associated with the pathogenesis of leukemia. Nevertheless, it is very necessary to continue the profound study of the pathogenesis of leukemia. Here, we propose a new mathematical model which include some negative feedback inhibition from the terminally differentiated cells of haematopoietic lineages to the haematopoietic stem cells and haematopoietic progenitor cells in order to describe the regulatory mechanisms mentioned above by a set of ordinary differential equations. Afterwards, we carried out detailed dynamical bifurcation analysis of the model, and obtained some meaningful results.

RESULTS: In this work, we mainly perform the analysis of the mathematic model by bifurcation theory and numerical simulations. We have not only incorporated some new negative feedback mechanisms to the existing model, but also constructed our own model by using the modeling method of stem cell theory with probability method. Through a series of qualitative analysis and numerical simulations, we obtain that the weak negative feedback for differentiation probability is conducive to the cure of leukemia. However, with the strengthening of negative feedback, leukemia will be more difficult to be cured, and even induce death. In contrast, strong negative feedback for differentiation rate of progenitor cells can promote healthy haematopoiesis and suppress leukaemia.

CONCLUSIONS: These results demonstrate that healthy progenitor cells are bestowed a competitive advantage over leukaemia stem cells. Weak g1, g2, and h1 enable the system stays in the healthy state. However, strong h2 can promote healthy haematopoiesis and suppress leukaemia.}, } @article {pmid29745849, year = {2018}, author = {Lee, S and Kim, Y and Choi, S and Hwang, H and Park, T}, title = {Pathway-based approach using hierarchical components of rare variants to analyze multiple phenotypes.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {79}, pmid = {29745849}, issn = {1471-2105}, abstract = {BACKGROUND: As one possible solution to the "missing heritability" problem, many methods have been proposed that apply pathway-based analyses, using rare variants that are detected by next generation sequencing technology. However, while a number of methods for pathway-based rare-variant analysis of multiple phenotypes have been proposed, no method considers a unified model that incorporate multiple pathways.

RESULTS: Simulation studies successfully demonstrated advantages of multivariate analysis, compared to univariate analysis, and comparison studies showed the proposed approach to outperform existing methods. Moreover, real data analysis of six type 2 diabetes-related traits, using large-scale whole exome sequencing data, identified significant pathways that were not found by univariate analysis. Furthermore, strong relationships between the identified pathways, and their associated metabolic disorder risk factors, were found via literature search, and one of the identified pathway, was successfully replicated by an analysis with an independent dataset.

CONCLUSIONS: Herein, we present a powerful, pathway-based approach to investigate associations between multiple pathways and multiple phenotypes. By reflecting the natural hierarchy of biological behavior, and considering correlation between pathways and phenotypes, the proposed method is capable of analyzing multiple phenotypes and multiple pathways simultaneously.}, } @article {pmid29745848, year = {2018}, author = {Takenaka, Y and Mikami, K and Seno, S and Matsuda, H}, title = {Automated transition analysis of activated gene regulation during diauxic nutrient shift in Escherichia coli and adipocyte differentiation in mouse cells.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {89}, pmid = {29745848}, issn = {1471-2105}, abstract = {BACKGROUND: Comprehensively understanding the dynamics of biological systems is among the biggest current challenges in biology and medicine. To acquire this understanding, researchers have measured the time-series expression profiles of cell lines of various organisms. Biological technologies have also drastically improved, providing a huge amount of information with support from bioinformatics and systems biology. However, the transitions between the activation and inactivation of gene regulations, at the temporal resolution of single time points, are difficult to extract from time-course gene expression profiles.

RESULTS: Our proposed method reports the activation period of each gene regulation from gene expression profiles and a gene regulatory network. The correctness and effectiveness of the method were validated by analyzing the diauxic shift from glucose to lactose in Escherichia coli. The method completely detected the three periods of the shift; 1) consumption of glucose as nutrient source, 2) the period of seeking another nutrient source and 3) consumption of lactose as nutrient source. We then applied the method to mouse adipocyte differentiation data. Cell differentiation into adipocytes is known to involve two waves of the gene regulation cascade, and sub-waves are predicted. From the gene expression profiles of the cell differentiation process from ES to adipose cells (62 time points), our method acquired four periods; three periods covering the two known waves of the cascade, and a final period of gene regulations when the differentiation to adipocytes was completed.

CONCLUSIONS: Our proposed method identifies the transitions of gene regulations from time-series gene expression profiles. Dynamic analyses are essential for deep understanding of biological systems and for identifying the causes of the onset of diseases such as diabetes and osteoporosis. The proposed method can greatly contribute to the progress of biology and medicine.}, } @article {pmid29745847, year = {2018}, author = {Mai, U and Mirarab, S}, title = {TreeShrink: fast and accurate detection of outlier long branches in collections of phylogenetic trees.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 5}, pages = {272}, pmid = {29745847}, issn = {1471-2164}, support = {P30 AI027767/AI/NIAID NIH HHS/United States ; }, mesh = {*Algorithms ; Animals ; Computational Biology/*methods ; Datasets as Topic ; Genes ; Humans ; Mammals/*classification/*genetics ; Models, Genetic ; *Phylogeny ; Plants/classification/genetics ; *Software ; Species Specificity ; }, abstract = {BACKGROUND: Sequence data used in reconstructing phylogenetic trees may include various sources of error. Typically errors are detected at the sequence level, but when missed, the erroneous sequences often appear as unexpectedly long branches in the inferred phylogeny.

RESULTS: We propose an automatic method to detect such errors. We build a phylogeny including all the data then detect sequences that artificially inflate the tree diameter. We formulate an optimization problem, called the k-shrink problem, that seeks to find k leaves that could be removed to maximally reduce the tree diameter. We present an algorithm to find the exact solution for this problem in polynomial time. We then use several statistical tests to find outlier species that have an unexpectedly high impact on the tree diameter. These tests can use a single tree or a set of related gene trees and can also adjust to species-specific patterns of branch length. The resulting method is called TreeShrink. We test our method on six phylogenomic biological datasets and an HIV dataset and show that the method successfully detects and removes long branches. TreeShrink removes sequences more conservatively than rogue taxon removal and often reduces gene tree discordance more than rogue taxon removal once the amount of filtering is controlled.

CONCLUSIONS: TreeShrink is an effective method for detecting sequences that lead to unrealistically long branch lengths in phylogenetic trees. The tool is publicly available at https://github.com/uym2/TreeShrink .}, } @article {pmid29745846, year = {2018}, author = {Zhang, Y and Zheng, C and Sankoff, D}, title = {Pinning down ploidy in paleopolyploid plants.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 5}, pages = {287}, pmid = {29745846}, issn = {1471-2164}, mesh = {Brassica rapa/*genetics ; Chromosomes, Plant ; Evolution, Molecular ; *Gene Duplication ; *Genome, Plant ; Phylogeny ; *Ploidies ; Synteny ; }, abstract = {BACKGROUND: Fractionation is the genome-wide process of losing one gene per duplicate pair following whole genome multiplication (doubling, tripling, …). This is important in the evolution of plants over tens of millions of years, because of their repeated cycles of genome multiplication and fractionation. One type of evidence in the study of these processes is the frequency distribution of similarities between the two genes, over all the duplicate pairs in the genome.

RESULTS: We study modeling and inference problems around the processes of fractionation and whole genome multiplication focusing first on the frequency distribution of similarities of duplicate pairs in the genome. Our birth-and-death model accounts for repeated duplication, triplication or other multiplication events, as well as fractionation rates among multiple progeny of a single gene specific to each event. It also has a biologically and combinatorially well-motivated way of handling the tendency for at least one sibling to survive fractionation. The method settles previously unexplored questions about the expected number of gene pairs tracing their ancestry back to each multiplication event. We exemplify the algebraic concepts inherent in our models and on Brassica rapa, whose evolutionary history is well-known. We demonstrate the quantitative analysis of high-similarity gene pairs and triples to confirm the known ploidies of events in the lineage of B. rapa.

CONCLUSIONS: Our birth-and-death model accounts for the similarity distribution of paralogs in terms of multiple rounds of whole genome multiplication and fractionation. An analysis of high-similarity gene triples confirms the recent Brassica triplication.}, } @article {pmid29745845, year = {2018}, author = {Zou, XD and An, K and Wu, YD and Ye, ZQ}, title = {PPI network analyses of human WD40 protein family systematically reveal their tendency to assemble complexes and facilitate the complex predictions.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {41}, pmid = {29745845}, issn = {1752-0509}, abstract = {BACKGROUND: WD40 repeat proteins constitute one of the largest families in eukaryotes, and widely participate in various fundamental cellular processes by interacting with other molecules. Based on individual WD40 proteins, previous work has demonstrated that their structural characteristics should confer great potential of interaction and complex formation, and has speculated that they may serve as hubs in the protein-protein interaction (PPI) network. However, what roles the whole family plays in organizing the PPI network, and whether this information can be utilized in complex prediction remain unclear. To address these issues, quantitative and systematic analyses of WD40 proteins from the perspective of PPI networks are highly required.

RESULTS: In this work, we built two human PPI networks by using data sets with different confidence levels, and studied the network properties of the whole human WD40 protein family systematically. Our analyses have quantitatively confirmed that the human WD40 protein family, as a whole, tends to be hubs with an odds ratio of about 1.8 or greater, and the network decomposition has revealed that they are prone to enrich near the global center of the whole network with a fold change of two in the median k-values. By integrating expression profiles, we have further shown that WD40 hub proteins are inclined to be intramodular, which is indicative of complex assembling. Based on this information, we have further predicted 1674 potential WD40-associated complexes by choosing a clique-based method, which is more sensitive than others, and an indirect evaluation by co-expression scores has demonstrated its reliability.

CONCLUSIONS: At the systems level but not sporadic examples' level, this work has provided rich knowledge for better understanding WD40 proteins' roles in organizing the PPI network. These findings and predicted complexes can offer valuable clues for prioritizing candidates for further studies.}, } @article {pmid29745844, year = {2018}, author = {Paszek, J and Górecki, P}, title = {Inferring duplication episodes from unrooted gene trees.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 5}, pages = {288}, pmid = {29745844}, issn = {1471-2164}, mesh = {*Algorithms ; Animals ; Computational Biology ; Evolution, Molecular ; *Gene Duplication ; *Genome ; Genomics ; *Models, Genetic ; *Phylogeny ; }, abstract = {BACKGROUND: One of evolutionary molecular biology fundamental issues is to discover genomic duplication events and their correspondence to the species tree. Such events can be reconstructed by clustering single gene duplications inferred by reconciling a set of gene trees with a species tree.

RESULTS: Here we propose the first solutions to the genomic duplication problem in which every reconciliation with the minimal number of single gene duplications is allowed and the method of clustering called minimum episodes under the assumption that input gene trees are unrooted.

CONCLUSIONS: We showed new theoretical properties of unrooted reconciliation for the duplication cost and apply them to design several exact and heuristic algorithms for solving the problem. Our evaluation study on empirical dataset confirmed several genomic duplication events from the literature and demonstrate that algorithms can be successfully applied.}, } @article {pmid29745843, year = {2018}, author = {Kim, Y and Lee, S and Choi, S and Jang, JY and Park, T}, title = {Hierarchical structural component modeling of microRNA-mRNA integration analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {75}, pmid = {29745843}, issn = {1471-2105}, abstract = {BACKGROUND: Identification of multi-markers is one of the most challenging issues in personalized medicine era. Nowadays, many different types of omics data are generated from the same subject. Although many methods endeavor to identify candidate markers, for each type of omics data, few or none can facilitate such identification.

RESULTS: It is well known that microRNAs affect phenotypes only indirectly, through regulating mRNA expression and/or protein translation. Toward addressing this issue, we suggest a hierarchical structured component analysis of microRNA-mRNA integration ("HisCoM-mimi") model that accounts for this biological relationship, to efficiently study and identify such integrated markers. In simulation studies, HisCoM-mimi showed the better performance than the other three methods. Also, in real data analysis, HisCoM-mimi successfully identified more gives more informative miRNA-mRNA integration sets relationships for pancreatic ductal adenocarcinoma (PDAC) diagnosis, compared to the other methods.

CONCLUSION: As exemplified by an application to pancreatic cancer data, our proposed model effectively identified integrated miRNA/target mRNA pairs as markers for early diagnosis, providing a much broader biological interpretation.}, } @article {pmid29745842, year = {2018}, author = {Hung, KS and Hsiao, CC and Pai, TW and Hu, CH and Tzou, WS and Wang, WD and Chen, YR}, title = {Functional enrichment analysis based on long noncoding RNA associations.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {45}, pmid = {29745842}, issn = {1752-0509}, abstract = {BACKGROUND: Differential gene expression analysis using RNA-seq data is a popular approach for discovering specific regulation mechanisms under certain environmental settings. Both gene ontology (GO) and KEGG pathway enrichment analysis are major processes for investigating gene groups that participate in common biological responses or possess related functions. However, traditional approaches based on differentially expressed genes only detect a few significant GO terms and pathways, which are frequently insufficient to explain all-inclusive gene regulation mechanisms.

METHODS: Transcriptomes of survivin (birc5) gene knock-down experimental and wild-type control zebrafish embryos were sequenced and assembled, and a differential expression (DE) gene list was obtained for traditional functional enrichment analysis. In addition to including DE genes with significant fold-change levels, we considered additional associated genes near or overlapped with differentially expressed long noncoding RNAs (DE lncRNAs), which may directly or indirectly activate or inhibit target genes and play important roles in regulation networks. Both the original DE gene list and the additional DE lncRNA-associated genes were combined to perform a comprehensive overrepresentation analysis.

RESULTS: In this study, a total of 638 DE genes and 616 DE lncRNA-associated genes (lncGenes) were leveraged simultaneously in searching for significant GO terms and KEGG pathways. Compared to the traditional approach of only using a differential expression gene list, the proposed method of employing DE lncRNA-associated genes identified several additional important GO terms and KEGG pathways. In GO enrichment analysis, 60% more GO terms were obtained, and several neuron development functional terms were retrieved as complete annotations. We also observed that additional important pathways such as the FoxO and MAPK signaling pathways were retrieved, which were shown in previous reports to play important roles in apoptosis and neuron development functions regulated by the survivin gene.

CONCLUSIONS: We demonstrated that incorporating genes near or overlapped with DE lncRNAs into the DE gene list outperformed the traditional enrichment analysis method for effective biological functional interpretations. These hidden interactions between lncRNAs and target genes could facilitate more comprehensive analyses.}, } @article {pmid29745841, year = {2018}, author = {Cui, F and Yuan, B}, title = {Fixation probability of a beneficial mutation conferring decreased generation time in changing environments.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {48}, pmid = {29745841}, issn = {1752-0509}, abstract = {BACKGROUND: One central building block of population genetics is the fixation probability. It is a probabilistic understanding of the eventual fate of new mutations. Moreover, the fixation probability of new beneficial mutations plays an important effect on the adaptation of populations to environmental challenges. Great progress has been made in the study of the beneficial mutations that increases offspring number. However, the fixation probability of beneficial mutations with a shorter generation time under various genetic and ecological conditions has not been explored.

RESULTS: Here we extend the classical result of the fixation probability of beneficial mutations obtained by Haldane, and estimate the fixation probability of a beneficial mutation with a reduced generation time in a changing environment. Assuming that the selective advantage is very small, we concentrate all the changing factors of environment on a single quantity: effective selective advantage. Using a time-dependent branching process, we get the analytic approximation for the fixation probability of beneficial mutations that decrease the generation time. Then, we apply this approximation to four interesting biological cases.

CONCLUSIONS: In these instances, we show the comparison of the approximation with the accurate values. We find that they are consistent, demonstrating the effectiveness of our result for the fixation probability of beneficial mutations conferring a reduced replication time.}, } @article {pmid29745840, year = {2018}, author = {Fu, M and Wu, W and Hong, X and Liu, Q and Jiang, J and Ou, Y and Zhao, Y and Gong, X}, title = {Hierarchical combinatorial deep learning architecture for pancreas segmentation of medical computed tomography cancer images.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {56}, pmid = {29745840}, issn = {1752-0509}, abstract = {BACKGROUND: Efficient computational recognition and segmentation of target organ from medical images are foundational in diagnosis and treatment, especially about pancreas cancer. In practice, the diversity in appearance of pancreas and organs in abdomen, makes detailed texture information of objects important in segmentation algorithm. According to our observations, however, the structures of previous networks, such as the Richer Feature Convolutional Network (RCF), are too coarse to segment the object (pancreas) accurately, especially the edge.

METHOD: In this paper, we extend the RCF, proposed to the field of edge detection, for the challenging pancreas segmentation, and put forward a novel pancreas segmentation network. By employing multi-layer up-sampling structure replacing the simple up-sampling operation in all stages, the proposed network fully considers the multi-scale detailed contexture information of object (pancreas) to perform per-pixel segmentation. Additionally, using the CT scans, we supply and train our network, thus get an effective pipeline.

RESULT: Working with our pipeline with multi-layer up-sampling model, we achieve better performance than RCF in the task of single object (pancreas) segmentation. Besides, combining with multi scale input, we achieve the 76.36% DSC (Dice Similarity Coefficient) value in testing data.

CONCLUSION: The results of our experiments show that our advanced model works better than previous networks in our dataset. On the other words, it has better ability in catching detailed contexture information. Therefore, our new single object segmentation model has practical meaning in computational automatic diagnosis.}, } @article {pmid29745839, year = {2018}, author = {Li, L and He, X and Borgwardt, K}, title = {Multi-target drug repositioning by bipartite block-wise sparse multi-task learning.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {55}, pmid = {29745839}, issn = {1752-0509}, abstract = {BACKGROUND: Finding potential drug targets is a crucial step in drug discovery and development. Recently, resources such as the Library of Integrated Network-Based Cellular Signatures (LINCS) L1000 database provide gene expression profiles induced by various chemical and genetic perturbations and thereby make it possible to analyze the relationship between compounds and gene targets at a genome-wide scale. Current approaches for comparing the expression profiles are based on pairwise connectivity mapping analysis. However, this method makes the simple assumption that the effect of a drug treatment is similar to knocking down its single target gene. Since many compounds can bind multiple targets, the pairwise mapping ignores the combined effects of multiple targets, and therefore fails to detect many potential targets of the compounds.

RESULTS: We propose an algorithm to find sets of gene knock-downs that induce gene expression changes similar to a drug treatment. Assuming that the effects of gene knock-downs are additive, we propose a novel bipartite block-wise sparse multi-task learning model with super-graph structure (BBSS-MTL) for multi-target drug repositioning that overcomes the restrictive assumptions of connectivity mapping analysis.

CONCLUSIONS: The proposed method BBSS-MTL is more accurate for predicting potential drug targets than the simple pairwise connectivity mapping analysis on five datasets generated from different cancer cell lines.

AVAILABILITY: The code can be obtained at http://gr.xjtu.edu.cn/web/liminli/codes .}, } @article {pmid29745838, year = {2018}, author = {Lei, X and Fang, M and Wu, FX and Chen, L}, title = {Improved flower pollination algorithm for identifying essential proteins.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {46}, pmid = {29745838}, issn = {1752-0509}, abstract = {BACKGROUND: Essential proteins are necessary for the survival and development of cells. The identification of essential proteins can help to understand the minimal requirements for cellular life and it also plays an important role in the disease genes study and drug design. With the development of high-throughput techniques, a large amount of protein-protein interactions data is available to predict essential proteins at the network level. Hitherto, even though a number of essential protein discovery methods have been proposed, the prediction precision still needs to be improved.

METHODS: In this paper, we propose a new algorithm, improved Flower Pollination algorithm (FPA) for identifying Essential proteins, named FPE. Different from other existing essential protein discovery methods, we apply FPA which is a new intelligent algorithm imitating pollination behavior of flowering plants in nature to identify essential proteins. Analogous to flower pollination is to find optimal reproduction from the perspective of biological evolution, and the identification of essential proteins is to discover a candidate essential protein set by analyzing the corresponding relationships between FPA algorithm and the prediction of essential proteins, and redefining the positions of flowers and specific pollination process. Moreover, it has been proved that the integration of biological and topological properties can get improved precision for identifying essential proteins. Consequently, we develop a GSC measurement in order to judge the essentiality of proteins, which takes into account not only the Gene expression data, Subcellular localization and protein Complexes information, but also the network topology.

RESULTS: The experimental results show that FPE performs better than the state-of-the-art methods (DC, SC, IC, EC, LAC, NC, PeC, WDC, UDoNC and SON) in terms of the prediction precision, precision-recall curve and jackknife curve for identifying essential proteins and also has high stability.

CONCLUSIONS: We confirm that FPE can be used to effectively identify essential proteins by the use of nature-inspired algorithm FPA and the combination of network topology with gene expression data, subcellular localization and protein complexes information. The experimental results have shown the superiority of FPE for the prediction of essential proteins.}, } @article {pmid29745837, year = {2018}, author = {Zhou, J and Wang, H and Zhao, Z and Xu, R and Lu, Q}, title = {CNNH_PSS: protein 8-class secondary structure prediction by convolutional neural network with highway.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {60}, pmid = {29745837}, issn = {1471-2105}, abstract = {BACKGROUND: Protein secondary structure is the three dimensional form of local segments of proteins and its prediction is an important problem in protein tertiary structure prediction. Developing computational approaches for protein secondary structure prediction is becoming increasingly urgent.

RESULTS: We present a novel deep learning based model, referred to as CNNH_PSS, by using multi-scale CNN with highway. In CNNH_PSS, any two neighbor convolutional layers have a highway to deliver information from current layer to the output of the next one to keep local contexts. As lower layers extract local context while higher layers extract long-range interdependencies, the highways between neighbor layers allow CNNH_PSS to have ability to extract both local contexts and long-range interdependencies. We evaluate CNNH_PSS on two commonly used datasets: CB6133 and CB513. CNNH_PSS outperforms the multi-scale CNN without highway by at least 0.010 Q8 accuracy and also performs better than CNF, DeepCNF and SSpro8, which cannot extract long-range interdependencies, by at least 0.020 Q8 accuracy, demonstrating that both local contexts and long-range interdependencies are indeed useful for prediction. Furthermore, CNNH_PSS also performs better than GSM and DCRNN which need extra complex model to extract long-range interdependencies. It demonstrates that CNNH_PSS not only cost less computer resource, but also achieves better predicting performance.

CONCLUSION: CNNH_PSS have ability to extracts both local contexts and long-range interdependencies by combing multi-scale CNN and highway network. The evaluations on common datasets and comparisons with state-of-the-art methods indicate that CNNH_PSS is an useful and efficient tool for protein secondary structure prediction.}, } @article {pmid29745835, year = {2018}, author = {Schulz, T and Stoye, J and Doerr, D}, title = {GraphTeams: a method for discovering spatial gene clusters in Hi-C sequencing data.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 5}, pages = {308}, pmid = {29745835}, issn = {1471-2164}, mesh = {*Algorithms ; Animals ; Chromosomes/*chemistry ; Cluster Analysis ; *Computer Graphics ; Genomics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mice ; *Multigene Family ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Hi-C sequencing offers novel, cost-effective means to study the spatial conformation of chromosomes. We use data obtained from Hi-C experiments to provide new evidence for the existence of spatial gene clusters. These are sets of genes with associated functionality that exhibit close proximity to each other in the spatial conformation of chromosomes across several related species.

RESULTS: We present the first gene cluster model capable of handling spatial data. Our model generalizes a popular computational model for gene cluster prediction, called δ-teams, from sequences to graphs. Following previous lines of research, we subsequently extend our model to allow for several vertices being associated with the same label. The model, called δ-teams with families, is particular suitable for our application as it enables handling of gene duplicates. We develop algorithmic solutions for both models. We implemented the algorithm for discovering δ-teams with families and integrated it into a fully automated workflow for discovering gene clusters in Hi-C data, called GraphTeams. We applied it to human and mouse data to find intra- and interchromosomal gene cluster candidates. The results include intrachromosomal clusters that seem to exhibit a closer proximity in space than on their chromosomal DNA sequence. We further discovered interchromosomal gene clusters that contain genes from different chromosomes within the human genome, but are located on a single chromosome in mouse.

CONCLUSIONS: By identifying δ-teams with families, we provide a flexible model to discover gene cluster candidates in Hi-C data. Our analysis of Hi-C data from human and mouse reveals several known gene clusters (thus validating our approach), but also few sparsely studied or possibly unknown gene cluster candidates that could be the source of further experimental investigations.}, } @article {pmid29745833, year = {2018}, author = {Dai, W and Li, Q and Liu, BY and Li, YX and Li, YY}, title = {Differential networking meta-analysis of gastric cancer across Asian and American racial groups.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {51}, pmid = {29745833}, issn = {1752-0509}, abstract = {BACKGROUND: Gastric Carcinoma is one of the most lethal cancer around the world, and is also the most common cancers in Eastern Asia. A lot of differentially expressed genes have been detected as being associated with Gastric Carcinoma (GC) progression, however, little is known about the underlying dysfunctional regulation mechanisms. To address this problem, we previously developed a differential networking approach that is characterized by involving differential coexpression analysis (DCEA), stage-specific gene regulatory network (GRN) modelling and differential regulation networking (DRN) analysis.

RESULT: In order to implement differential networking meta-analysis, we developed a novel framework which integrated the following steps. Considering the complexity and diversity of gastric carcinogenesis, we first collected three datasets (GSE54129, GSE24375 and TCGA-STAD) for Chinese, Korean and American, and aimed to investigate the common dysregulation mechanisms of gastric carcinogenesis across racial groups. Then, we constructed conditional GRNs for gastric cancer corresponding to normal and carcinoma, and prioritized differentially regulated genes (DRGs) and gene links (DRLs) from three datasets separately by using our previously developed differential networking method. Based on our integrated differential regulation information from three datasets and prior knowledge (e.g., transcription factor (TF)-target regulatory relationships and known signaling pathways), we eventually generated testable hypotheses on the regulation mechanisms of two genes, XBP1 and GIF, out of 16 common cross-racial DRGs in gastric carcinogenesis.

CONCLUSION: The current cross-racial integrative study from the viewpoint of differential regulation networking provided useful clues for understanding the common dysfunctional regulation mechanisms of gastric cancer progression and discovering new universal drug targets or biomarkers for gastric cancer.}, } @article {pmid29745832, year = {2018}, author = {Yang, S and Guo, R and Liu, R and Liao, X and Zou, Q and Shi, B and Peng, S}, title = {cmFSM: a scalable CPU-MIC coordinated drug-finding tool by frequent subgraph mining.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {98}, doi = {10.1186/s12859-018-2071-z}, pmid = {29745832}, issn = {1471-2105}, abstract = {BACKGROUND: Frequent subgraphs mining is a significant problem in many practical domains. The solution of this kind of problem can particularly used in some large-scale drug molecular or biological libraries to help us find drugs or core biological structures rapidly and predict toxicity of some unknown compounds. The main challenge is its efficiency, as (i) it is computationally intensive to test for graph isomorphisms, and (ii) the graph collection to be mined and mining results can be very large. Existing solutions often require days to derive mining results from biological networks even with relative low support threshold. Also, the whole mining results always cannot be stored in single node memory.

RESULTS: In this paper, we implement a parallel acceleration tool for classical frequent subgraph mining algorithm called cmFSM. The core idea is to employ parallel techniques to parallelize extension tasks, so as to reduce computation time. On the other hand, we employ multi-node strategy to solve the problem of memory constraints. The parallel optimization of cmFSM is carried out on three different levels, including the fine-grained OpenMP parallelization on single node, multi-node multi-process parallel acceleration and CPU-MIC collaborated parallel optimization.

CONCLUSIONS: Evaluation results show that cmFSM clearly outperforms the existing state-of-the-art miners even if we only hold a few parallel computing resources. It means that cmFSM provides a practical solution to frequent subgraph mining problem with huge number of mining results. Specifically, our solution is up to one order of magnitude faster than the best CPU-based approach on single node and presents a promising scalability of massive mining tasks in multi-node scenario. More source code are available at:Source Code: https://github.com/ysycloud/cmFSM .}, } @article {pmid29745831, year = {2018}, author = {Wang, Y and Zhang, XS and Chen, L}, title = {Integrating data- and model-driven strategies in systems biology.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 4}, pages = {38}, pmid = {29745831}, issn = {1752-0509}, abstract = {A report of the 11th International Conference on Systems Biology (ISB2017), 18-21 August, Shenzhen, China.}, } @article {pmid29745830, year = {2018}, author = {Hayashi, T and Matsuzaki, Y and Yanagisawa, K and Ohue, M and Akiyama, Y}, title = {MEGADOCK-Web: an integrated database of high-throughput structure-based protein-protein interaction predictions.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {62}, pmid = {29745830}, issn = {1471-2105}, abstract = {BACKGROUND: Protein-protein interactions (PPIs) play several roles in living cells, and computational PPI prediction is a major focus of many researchers. The three-dimensional (3D) structure and binding surface are important for the design of PPI inhibitors. Therefore, rigid body protein-protein docking calculations for two protein structures are expected to allow elucidation of PPIs different from known complexes in terms of 3D structures because known PPI information is not explicitly required. We have developed rapid PPI prediction software based on protein-protein docking, called MEGADOCK. In order to fully utilize the benefits of computational PPI predictions, it is necessary to construct a comprehensive database to gather prediction results and their predicted 3D complex structures and to make them easily accessible. Although several databases exist that provide predicted PPIs, the previous databases do not contain a sufficient number of entries for the purpose of discovering novel PPIs.

RESULTS: In this study, we constructed an integrated database of MEGADOCK PPI predictions, named MEGADOCK-Web. MEGADOCK-Web provides more than 10 times the number of PPI predictions than previous databases and enables users to conduct PPI predictions that cannot be found in conventional PPI prediction databases. In MEGADOCK-Web, there are 7528 protein chains and 28,331,628 predicted PPIs from all possible combinations of those proteins. Each protein structure is annotated with PDB ID, chain ID, UniProt AC, related KEGG pathway IDs, and known PPI pairs. Additionally, MEGADOCK-Web provides four powerful functions: 1) searching precalculated PPI predictions, 2) providing annotations for each predicted protein pair with an experimentally known PPI, 3) visualizing candidates that may interact with the query protein on biochemical pathways, and 4) visualizing predicted complex structures through a 3D molecular viewer.

CONCLUSION: MEGADOCK-Web provides a huge amount of comprehensive PPI predictions based on docking calculations with biochemical pathways and enables users to easily and quickly assess PPI feasibilities by archiving PPI predictions. MEGADOCK-Web also promotes the discovery of new PPIs and protein functions and is freely available for use at http://www.bi.cs.titech.ac.jp/megadock-web/ .}, } @article {pmid29745829, year = {2018}, author = {Chen, SH and Kuo, WY and Su, SY and Chung, WC and Ho, JM and Lu, HH and Lin, CY}, title = {A gene profiling deconvolution approach to estimating immune cell composition from complex tissues.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {154}, pmid = {29745829}, issn = {1471-2105}, abstract = {BACKGROUND: A new emerged cancer treatment utilizes intrinsic immune surveillance mechanism that is silenced by those malicious cells. Hence, studies of tumor infiltrating lymphocyte populations (TILs) are key to the success of advanced treatments. In addition to laboratory methods such as immunohistochemistry and flow cytometry, in silico gene expression deconvolution methods are available for analyses of relative proportions of immune cell types.

RESULTS: Herein, we used microarray data from the public domain to profile gene expression pattern of twenty-two immune cell types. Initially, outliers were detected based on the consistency of gene profiling clustering results and the original cell phenotype notation. Subsequently, we filtered out genes that are expressed in non-hematopoietic normal tissues and cancer cells. For every pair of immune cell types, we ran t-tests for each gene, and defined differentially expressed genes (DEGs) from this comparison. Equal numbers of DEGs were then collected as candidate lists and numbers of conditions and minimal values for building signature matrixes were calculated. Finally, we used v -Support Vector Regression to construct a deconvolution model. The performance of our system was finally evaluated using blood biopsies from 20 adults, in which 9 immune cell types were identified using flow cytometry. The present computations performed better than current state-of-the-art deconvolution methods.

CONCLUSIONS: Finally, we implemented the proposed method into R and tested extensibility and usability on Windows, MacOS, and Linux operating systems. The method, MySort, is wrapped as the Galaxy platform pluggable tool and usage details are available at https://testtoolshed.g2.bx.psu.edu/view/moneycat/mysort/e3afe097e80a .}, } @article {pmid29745828, year = {2018}, author = {Gao, Y and Wang, S and Deng, M and Xu, J}, title = {RaptorX-Angle: real-value prediction of protein backbone dihedral angles through a hybrid method of clustering and deep learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {100}, pmid = {29745828}, issn = {1471-2105}, support = {R01 GM089753/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Protein dihedral angles provide a detailed description of protein local conformation. Predicted dihedral angles can be used to narrow down the conformational space of the whole polypeptide chain significantly, thus aiding protein tertiary structure prediction. However, direct angle prediction from sequence alone is challenging.

RESULTS: In this article, we present a novel method (named RaptorX-Angle) to predict real-valued angles by combining clustering and deep learning. Tested on a subset of PDB25 and the targets in the latest two Critical Assessment of protein Structure Prediction (CASP), our method outperforms the existing state-of-art method SPIDER2 in terms of Pearson Correlation Coefficient (PCC) and Mean Absolute Error (MAE). Our result also shows approximately linear relationship between the real prediction errors and our estimated bounds. That is, the real prediction error can be well approximated by our estimated bounds.

CONCLUSIONS: Our study provides an alternative and more accurate prediction of dihedral angles, which may facilitate protein structure prediction and functional study.}, } @article {pmid29745827, year = {2018}, author = {Taguchi, YH}, title = {Tensor decomposition-based and principal-component-analysis-based unsupervised feature extraction applied to the gene expression and methylation profiles in the brains of social insects with multiple castes.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 4}, pages = {99}, pmid = {29745827}, issn = {1471-2105}, abstract = {BACKGROUND: Even though coexistence of multiple phenotypes sharing the same genomic background is interesting, it remains incompletely understood. Epigenomic profiles may represent key factors, with unknown contributions to the development of multiple phenotypes, and social-insect castes are a good model for elucidation of the underlying mechanisms. Nonetheless, previous studies have failed to identify genes associated with aberrant gene expression and methylation profiles because of the lack of suitable methodology that can address this problem properly.

METHODS: A recently proposed principal component analysis (PCA)-based and tensor decomposition (TD)-based unsupervised feature extraction (FE) can solve this problem because these two approaches can deal with gene expression and methylation profiles even when a small number of samples is available.

RESULTS: PCA-based and TD-based unsupervised FE methods were applied to the analysis of gene expression and methylation profiles in the brains of two social insects, Polistes canadensis and Dinoponera quadriceps. Genes associated with differential expression and methylation between castes were identified, and analysis of enrichment of Gene Ontology terms confirmed reliability of the obtained sets of genes from the biological standpoint.

CONCLUSIONS: Biologically relevant genes, shown to be associated with significant differential gene expression and methylation between castes, were identified here for the first time. The identification of these genes may help understand the mechanisms underlying epigenetic control of development of multiple phenotypes under the same genomic conditions.}, } @article {pmid29745026, year = {2018}, author = {De Vrieze, J and Boon, N and Verstraete, W}, title = {Taking the technical microbiome into the next decade.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14269}, pmid = {29745026}, issn = {1462-2920}, abstract = {The 'microbiome' has become a buzzword. Multiple new technologies allow to gather information about microbial communities as they evolve under stable and variable environmental conditions. The challenge of the next decade will be to develop strategies to compose and manage microbiomes. Here, key aspects are considered that will be of crucial importance for future microbial technological developments. First, the need to deal not only with genotypes but also particularly with phenotypes is addressed. Microbial technologies are often highly dependent on specific core organisms to obtain the desired process outcome. Hence, it is essential to combine omics data with phenotypic information to invoke and control specific phenotypes in the microbiome. Second, the development and application of synthetic microbiomes is evaluated. The central importance of the core species is a no-brainer, but the implementation of proper satellite species is an important route to explore. Overall, for the next decade, microbiome research should no longer almost exclusively focus on its capacity to degrade and dissipate but rather on its remarkable capability to capture disordered components and upgrade them into high-value microbial products. These products can become valuable commodities in the cyclic economy, as reflected in the case of 'reversed sanitation', which is introduced here.}, } @article {pmid29744990, year = {2018}, author = {}, title = {Corrigendum: A multigenerational effect of parental age on offspring size but not fitness in common duckweed (Lemna minor).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {779}, doi = {10.1111/jeb.13276}, pmid = {29744990}, issn = {1420-9101}, } @article {pmid29743716, year = {2018}, author = {}, title = {Deadly dust storms, insect diseases and Nature's new editor.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {144-145}, doi = {10.1038/d41586-018-05077-1}, pmid = {29743716}, issn = {1476-4687}, } @article {pmid29743715, year = {2018}, author = {Hodson, R}, title = {How robots are grasping the art of gripping.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S23-S25}, doi = {10.1038/d41586-018-05093-1}, pmid = {29743715}, issn = {1476-4687}, mesh = {Biomimetics/instrumentation/methods/*trends ; Commerce/economics ; Hand/physiology ; *Hand Strength/physiology ; Humans ; Machine Learning/trends ; Motion ; Neural Networks (Computer) ; Pliability ; Robotics/*instrumentation/*methods/trends ; Software ; Surface Properties ; Workforce ; }, } @article {pmid29743714, year = {2018}, author = {Nogrady, B}, title = {Australia makes its mark in biotechnology.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S27-S29}, doi = {10.1038/d41586-018-05092-2}, pmid = {29743714}, issn = {1476-4687}, mesh = {Australia ; Biotechnology/*economics/*trends ; Investments ; }, } @article {pmid29743713, year = {2018}, author = {Heffernan, O}, title = {How to save the high seas.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {154-156}, doi = {10.1038/d41586-018-05079-z}, pmid = {29743713}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms ; Conservation of Natural Resources/*legislation & jurisprudence/trends ; *Ecosystem ; Environmental Monitoring/legislation & jurisprudence/methods ; Fisheries/legislation & jurisprudence ; Fishes ; International Cooperation/*legislation & jurisprudence ; *Oceans and Seas ; United Nations/legislation & jurisprudence ; }, } @article {pmid29743711, year = {2018}, author = {Gleiser, M}, title = {How Much Can We Know?.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S20-S21}, doi = {10.1038/d41586-018-05100-5}, pmid = {29743711}, issn = {1476-4687}, mesh = {Animals ; Astronomy ; Consciousness/physiology ; Data Collection/methods ; Humans ; *Knowledge ; *Nature ; Origin of Life ; *Philosophy ; Physics ; *Research Design ; *Uncertainty ; }, } @article {pmid29743710, year = {2018}, author = {Musser, G}, title = {What Is Spacetime?.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S3-S6}, doi = {10.1038/d41586-018-05095-z}, pmid = {29743710}, issn = {1476-4687}, } @article {pmid29743709, year = {2018}, author = {Szostak, J}, title = {How Did Life Begin?.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S13-S15}, doi = {10.1038/d41586-018-05098-w}, pmid = {29743709}, issn = {1476-4687}, mesh = {Animals ; *Earth (Planet) ; *Evolution, Chemical ; Extraterrestrial Environment/*chemistry ; Humans ; *Origin of Life ; RNA/chemical synthesis/chemistry/genetics/metabolism ; Telescopes ; }, } @article {pmid29743708, year = {2018}, author = {Randall, L}, title = {What Is Dark Matter?.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S6-S7}, doi = {10.1038/d41586-018-05096-y}, pmid = {29743708}, issn = {1476-4687}, } @article {pmid29743707, year = {2018}, author = {Mukerjee, M}, title = {Looking at the Stars.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S2}, doi = {10.1038/d41586-018-05101-4}, pmid = {29743707}, issn = {1476-4687}, } @article {pmid29743706, year = {2018}, author = {Savage, N}, title = {What Are the Limits of Manipulating Nature?.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S16-S20}, doi = {10.1038/d41586-018-05099-9}, pmid = {29743706}, issn = {1476-4687}, } @article {pmid29743705, year = {2018}, author = {Koch, C}, title = {What Is Consciousness?.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {S8-S12}, doi = {10.1038/d41586-018-05097-x}, pmid = {29743705}, issn = {1476-4687}, mesh = {Animals ; Cerebellum/physiology/surgery ; Cerebral Cortex/*anatomy & histology/cytology/*physiology ; Cognition/physiology ; Consciousness/*physiology ; Electric Stimulation ; Electroencephalography ; Feedback, Physiological ; Gray Matter/cytology/physiology ; Humans ; Life ; Mind-Body Relations, Metaphysical ; Models, Neurological ; *Neurosciences/trends ; Philosophy ; Sensation/physiology ; Spinal Cord/cytology/physiology ; }, } @article {pmid29743704, year = {2018}, author = {}, title = {Crowdsourced quantum reality-check gets crowdsourced peer review.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {139-140}, doi = {10.1038/d41586-018-05073-5}, pmid = {29743704}, issn = {1476-4687}, mesh = {*Crowdsourcing ; *Peer Review ; }, } @article {pmid29743703, year = {2018}, author = {}, title = {What to do to improve postgraduate mental health.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {140}, doi = {10.1038/d41586-018-05074-4}, pmid = {29743703}, issn = {1476-4687}, } @article {pmid29743702, year = {2018}, author = {}, title = {The #MeToo campaign is gaining ground in China.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {139}, doi = {10.1038/d41586-018-05075-3}, pmid = {29743702}, issn = {1476-4687}, mesh = {China ; *Ethics, Professional/history ; Faculty/legislation & jurisprudence ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; *Public Opinion ; Sexual Harassment/history/*legislation & jurisprudence/*prevention & control ; Students/psychology/statistics & numerical data ; Universities ; }, } @article {pmid29743701, year = {2018}, author = {Marín-Spiotta, E}, title = {Harassment should count as scientific misconduct.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {141}, doi = {10.1038/d41586-018-05076-2}, pmid = {29743701}, issn = {1476-4687}, mesh = {Bullying/prevention & control/statistics & numerical data ; Faculty/legislation & jurisprudence/statistics & numerical data ; Female ; Humans ; Male ; Minority Groups/statistics & numerical data ; Research Personnel/ethics/*legislation & jurisprudence ; Scientific Misconduct/*classification/*legislation & jurisprudence ; Sexual Harassment/*legislation & jurisprudence/prevention & control ; Students/psychology/statistics & numerical data ; Universities ; Vulnerable Populations/statistics & numerical data ; Whistleblowing ; }, } @article {pmid29743700, year = {2018}, author = {Knepper, TC and McLeod, HL}, title = {When will clinical trials finally reflect diversity?.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {157-159}, doi = {10.1038/d41586-018-05049-5}, pmid = {29743700}, issn = {1476-4687}, mesh = {Central Nervous System Diseases ; Clinical Trials as Topic/economics/*ethics/*methods/statistics & numerical data ; Continental Population Groups/*statistics & numerical data ; Drug-Related Side Effects and Adverse Reactions/epidemiology ; Ethnic Groups/statistics & numerical data ; Geographic Mapping ; Health Services Accessibility/*trends ; Heart Diseases ; Humans ; Neoplasms ; Patient Selection/*ethics ; Racism/prevention & control/statistics & numerical data ; United States ; United States Food and Drug Administration/legislation & jurisprudence ; }, } @article {pmid29743699, year = {2018}, author = {Armstrong, A}, title = {Precarious preferences wipe out a butterfly population.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {171}, doi = {10.1038/d41586-018-05068-2}, pmid = {29743699}, issn = {1476-4687}, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; Butterflies/growth & development/*physiology ; Cattle ; *Extinction, Biological ; Female ; *Introduced Species ; Larva/growth & development ; Oviposition ; Plantago/*physiology ; Poaceae/growth & development/physiology ; Population Dynamics ; }, } @article {pmid29743697, year = {2018}, author = {Otte, A}, title = {A scholarly transformation in the life of Joseph Fourier.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {166}, doi = {10.1038/d41586-018-05064-6}, pmid = {29743697}, issn = {1476-4687}, } @article {pmid29743696, year = {2018}, author = {Ponraj, P}, title = {Next-generation sequencing may challenge antibody patent claims.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {166}, doi = {10.1038/d41586-018-05065-5}, pmid = {29743696}, issn = {1476-4687}, mesh = {Antibodies/*genetics ; *Biological Products ; DNA/genetics ; *High-Throughput Nucleotide Sequencing ; Humans ; Patents as Topic/*legislation & jurisprudence ; Supreme Court Decisions ; United States ; }, } @article {pmid29743695, year = {2018}, author = {Kawecki, M}, title = {Rethink wealth generated during cryptocurrency mining.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {166}, doi = {10.1038/d41586-018-05063-7}, pmid = {29743695}, issn = {1476-4687}, } @article {pmid29743694, year = {2018}, author = {Yeung, ACY}, title = {Arctic nations must adopt renewables to adapt to thaw.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {166}, doi = {10.1038/d41586-018-05066-4}, pmid = {29743694}, issn = {1476-4687}, } @article {pmid29743693, year = {2018}, author = {Karikari, TK and Amoateng, P}, title = {Kenya and Ghana set up national research funding schemes.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {166}, doi = {10.1038/d41586-018-05062-8}, pmid = {29743693}, issn = {1476-4687}, mesh = {Developing Countries/*economics ; *Federal Government ; Financing, Organized/economics/organization & administration ; Ghana ; Gross Domestic Product ; Humans ; Kenya ; Research/*economics/*organization & administration ; Research Support as Topic/*organization & administration ; }, } @article {pmid29743692, year = {2018}, author = {, }, title = {Precision measurement of the weak charge of the proton.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {207-211}, doi = {10.1038/s41586-018-0096-0}, pmid = {29743692}, issn = {1476-4687}, abstract = {Large experimental programmes in the fields of nuclear and particle physics search for evidence of physics beyond that explained by current theories. The observation of the Higgs boson completed the set of particles predicted by the standard model, which currently provides the best description of fundamental particles and forces. However, this theory's limitations include a failure to predict fundamental parameters, such as the mass of the Higgs boson, and the inability to account for dark matter and energy, gravity, and the matter-antimatter asymmetry in the Universe, among other phenomena. These limitations have inspired searches for physics beyond the standard model in the post-Higgs era through the direct production of additional particles at high-energy accelerators, which have so far been unsuccessful. Examples include searches for supersymmetric particles, which connect bosons (integer-spin particles) with fermions (half-integer-spin particles), and for leptoquarks, which mix the fundamental quarks with leptons. Alternatively, indirect searches using precise measurements of well predicted standard-model observables allow highly targeted alternative tests for physics beyond the standard model because they can reach mass and energy scales beyond those directly accessible by today's high-energy accelerators. Such an indirect search aims to determine the weak charge of the proton, which defines the strength of the proton's interaction with other particles via the well known neutral electroweak force. Because parity symmetry (invariance under the spatial inversion (x, y, z) → (-x, -y, -z)) is violated only in the weak interaction, it provides a tool with which to isolate the weak interaction and thus to measure the proton's weak charge 1 . Here we report the value 0.0719 ± 0.0045, where the uncertainty is one standard deviation, derived from our measured parity-violating asymmetry in the scattering of polarized electrons on protons, which is -226.5 ± 9.3 parts per billion (the uncertainty is one standard deviation). Our value for the proton's weak charge is in excellent agreement with the standard model 2 and sets multi-teraelectronvolt-scale constraints on any semi-leptonic parity-violating physics not described within the standard model. Our results show that precision parity-violating measurements enable searches for physics beyond the standard model that can compete with direct searches at high-energy accelerators and, together with astronomical observations, can provide fertile approaches to probing higher mass scales.}, } @article {pmid29743691, year = {2018}, author = {, }, title = {Challenging local realism with human choices.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {212-216}, doi = {10.1038/s41586-018-0085-3}, pmid = {29743691}, issn = {1476-4687}, mesh = {*Choice Behavior ; Freedom ; Geographic Mapping ; Humans ; Video Games ; }, abstract = {A Bell test is a randomized trial that compares experimental observations against the philosophical worldview of local realism 1 , in which the properties of the physical world are independent of our observation of them and no signal travels faster than light. A Bell test requires spatially distributed entanglement, fast and high-efficiency detection and unpredictable measurement settings2,3. Although technology can satisfy the first two of these requirements4-7, the use of physical devices to choose settings in a Bell test involves making assumptions about the physics that one aims to test. Bell himself noted this weakness in using physical setting choices and argued that human 'free will' could be used rigorously to ensure unpredictability in Bell tests 8 . Here we report a set of local-realism tests using human choices, which avoids assumptions about predictability in physics. We recruited about 100,000 human participants to play an online video game that incentivizes fast, sustained input of unpredictable selections and illustrates Bell-test methodology 9 . The participants generated 97,347,490 binary choices, which were directed via a scalable web platform to 12 laboratories on five continents, where 13 experiments tested local realism using photons5,6, single atoms 7 , atomic ensembles 10 and superconducting devices 11 . Over a 12-hour period on 30 November 2016, participants worldwide provided a sustained data flow of over 1,000 bits per second to the experiments, which used different human-generated data to choose each measurement setting. The observed correlations strongly contradict local realism and other realistic positions in bipartite and tripartite 12 scenarios. Project outcomes include closing the 'freedom-of-choice loophole' (the possibility that the setting choices are influenced by 'hidden variables' to correlate with the particle properties 13), the utilization of video-game methods 14 for rapid collection of human-generated randomness, and the use of networking techniques for global participation in experimental science.}, } @article {pmid29743690, year = {2018}, author = {Duan, C and Kee, RJ and Zhu, H and Karakaya, C and Chen, Y and Ricote, S and Jarry, A and Crumlin, EJ and Hook, D and Braun, R and Sullivan, NP and O'Hayre, R}, title = {Highly durable, coking and sulfur tolerant, fuel-flexible protonic ceramic fuel cells.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {217-222}, doi = {10.1038/s41586-018-0082-6}, pmid = {29743690}, issn = {1476-4687}, abstract = {Protonic ceramic fuel cells, like their higher-temperature solid-oxide fuel cell counterparts, can directly use both hydrogen and hydrocarbon fuels to produce electricity at potentially more than 50 per cent efficiency1,2. Most previous direct-hydrocarbon fuel cell research has focused on solid-oxide fuel cells based on oxygen-ion-conducting electrolytes, but carbon deposition (coking) and sulfur poisoning typically occur when such fuel cells are directly operated on hydrocarbon- and/or sulfur-containing fuels, resulting in severe performance degradation over time3-6. Despite studies suggesting good performance and anti-coking resistance in hydrocarbon-fuelled protonic ceramic fuel cells2,7,8, there have been no systematic studies of long-term durability. Here we present results from long-term testing of protonic ceramic fuel cells using a total of 11 different fuels (hydrogen, methane, domestic natural gas (with and without hydrogen sulfide), propane, n-butane, i-butane, iso-octane, methanol, ethanol and ammonia) at temperatures between 500 and 600 degrees Celsius. Several cells have been tested for over 6,000 hours, and we demonstrate excellent performance and exceptional durability (less than 1.5 per cent degradation per 1,000 hours in most cases) across all fuels without any modifications in the cell composition or architecture. Large fluctuations in temperature are tolerated, and coking is not observed even after thousands of hours of continuous operation. Finally, sulfur, a notorious poison for both low-temperature and high-temperature fuel cells, does not seem to affect the performance of protonic ceramic fuel cells when supplied at levels consistent with commercial fuels. The fuel flexibility and long-term durability demonstrated by the protonic ceramic fuel cell devices highlight the promise of this technology and its potential for commercial application.}, } @article {pmid29743689, year = {2018}, author = {Phan, TD and Eastwood, JP and Shay, MA and Drake, JF and Sonnerup, BUÖ and Fujimoto, M and Cassak, PA and Øieroset, M and Burch, JL and Torbert, RB and Rager, AC and Dorelli, JC and Gershman, DJ and Pollock, C and Pyakurel, PS and Haggerty, CC and Khotyaintsev, Y and Lavraud, B and Saito, Y and Oka, M and Ergun, RE and Retino, A and Le Contel, O and Argall, MR and Giles, BL and Moore, TE and Wilder, FD and Strangeway, RJ and Russell, CT and Lindqvist, PA and Magnes, W}, title = {Electron magnetic reconnection without ion coupling in Earth's turbulent magnetosheath.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {202-206}, doi = {10.1038/s41586-018-0091-5}, pmid = {29743689}, issn = {1476-4687}, abstract = {Magnetic reconnection in current sheets is a magnetic-to-particle energy conversion process that is fundamental to many space and laboratory plasma systems. In the standard model of reconnection, this process occurs in a minuscule electron-scale diffusion region1,2. On larger scales, ions couple to the newly reconnected magnetic-field lines and are ejected away from the diffusion region in the form of bi-directional ion jets at the ion Alfvén speed3-5. Much of the energy conversion occurs in spatially extended ion exhausts downstream of the diffusion region 6 . In turbulent plasmas, which contain a large number of small-scale current sheets, reconnection has long been suggested to have a major role in the dissipation of turbulent energy at kinetic scales7-11. However, evidence for reconnection plasma jetting in small-scale turbulent plasmas has so far been lacking. Here we report observations made in Earth's turbulent magnetosheath region (downstream of the bow shock) of an electron-scale current sheet in which diverging bi-directional super-ion-Alfvénic electron jets, parallel electric fields and enhanced magnetic-to-particle energy conversion were detected. Contrary to the standard model of reconnection, the thin reconnecting current sheet was not embedded in a wider ion-scale current layer and no ion jets were detected. Observations of this and other similar, but unidirectional, electron jet events without signatures of ion reconnection reveal a form of reconnection that can drive turbulent energy transfer and dissipation in electron-scale current sheets without ion coupling.}, } @article {pmid29743688, year = {2018}, author = {Singer, MC and Parmesan, C}, title = {Lethal trap created by adaptive evolutionary response to an exotic resource.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {238-241}, doi = {10.1038/s41586-018-0074-6}, pmid = {29743688}, issn = {1476-4687}, mesh = {*Adaptation, Physiological ; Animals ; *Biological Evolution ; Butterflies/growth & development/*physiology ; Cattle ; Domestication ; Extinction, Biological ; Female ; *Herbivory ; Human Activities ; Larva/growth & development/physiology ; North America ; Oviposition ; *Plantago ; Poaceae/growth & development ; }, abstract = {Global transport of organisms by humans provides novel resources to wild species, which often respond maladaptively. Native herbivorous insects have been killed feeding on toxic exotic plants, which acted as 'ecological traps'1-4. We document a novel 'eco-evolutionary trap' stemming from the opposite effect; that is, high fitness on an exotic resource despite lack of adaptation to it. Plantago lanceolata was introduced to western North America by cattle-ranching. Feeding on this exotic plant released a large, isolated population of the native butterfly Euphydryas editha from a longstanding trade-off between maternal fecundity and offspring mortality. Because of this release-and despite a reduced insect developmental rate when feeding on this exotic-Plantago immediately supported higher larval survival than did the insects' traditional host, Collinsia parviflora 5 . Previous work from the 1980s documented an evolving preference for Plantago by ovipositing adults 6 . We predicted that if this trend continued the insects could endanger themselves, because the availability of Plantago to butterflies is controlled by humans, who change land management practices faster than butterflies evolve 6 . Here we report the fulfilment of this prediction. The butterflies abandoned Collinsia and evolved total dependence on Plantago. The trap was set. In 2005, humans withdrew their cattle, springing the trap. Grasses grew around the Plantago, cooling the thermophilic insects, which then went extinct. This local extinction could have been prevented if the population had retained partial use of Collinsia, which occupied drier microhabitats unaffected by cattle removal. The flush of grasses abated quickly, rendering the meadow once again suitable for Euphydryas feeding on either host, but no butterflies were observed from 2008 to 2012. In 2013-2014, the site was naturally recolonized by Euphydryas feeding exclusively on Collinsia, returning the system to its starting point and setting the stage for a repeat of the anthropogenic evolutionary cycle.}, } @article {pmid29743687, year = {2018}, author = {Robertson, ID and Yourdkhani, M and Centellas, PJ and Aw, JE and Ivanoff, DG and Goli, E and Lloyd, EM and Dean, LM and Sottos, NR and Geubelle, PH and Moore, JS and White, SR}, title = {Rapid energy-efficient manufacturing of polymers and composites via frontal polymerization.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {223-227}, doi = {10.1038/s41586-018-0054-x}, pmid = {29743687}, issn = {1476-4687}, abstract = {Thermoset polymers and composite materials are integral to today's aerospace, automotive, marine and energy industries and will be vital to the next generation of lightweight, energy-efficient structures in these enterprises, owing to their excellent specific stiffness and strength, thermal stability and chemical resistance1-5. The manufacture of high-performance thermoset components requires the monomer to be cured at high temperatures (around 180 °C) for several hours, under a combined external pressure and internal vacuum 6 . Curing is generally accomplished using large autoclaves or ovens that scale in size with the component. Hence this traditional curing approach is slow, requires a large amount of energy and involves substantial capital investment6,7. Frontal polymerization is a promising alternative curing strategy, in which a self-propagating exothermic reaction wave transforms liquid monomers to fully cured polymers. We report here the frontal polymerization of a high-performance thermoset polymer that allows the rapid fabrication of parts with microscale features, three-dimensional printed structures and carbon-fibre-reinforced polymer composites. Precise control of the polymerization kinetics at both ambient and elevated temperatures allows stable monomer solutions to transform into fully cured polymers within seconds, reducing energy requirements and cure times by several orders of magnitude compared with conventional oven or autoclave curing approaches. The resulting polymer and composite parts possess similar mechanical properties to those cured conventionally. This curing strategy greatly improves the efficiency of manufacturing of high-performance polymers and composites, and is widely applicable to many industries.}, } @article {pmid29743679, year = {2018}, author = {Del Monte-Nieto, G and Ramialison, M and Adam, AAS and Wu, B and Aharonov, A and D'Uva, G and Bourke, LM and Pitulescu, ME and Chen, H and de la Pompa, JL and Shou, W and Adams, RH and Harten, SK and Tzahor, E and Zhou, B and Harvey, RP}, title = {Control of cardiac jelly dynamics by NOTCH1 and NRG1 defines the building plan for trabeculation.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {439-445}, doi = {10.1038/s41586-018-0110-6}, pmid = {29743679}, issn = {1476-4687}, mesh = {Animals ; Disease Models, Animal ; Endocardium/cytology/metabolism ; Extracellular Matrix/metabolism ; Heart/*embryology ; Heart Diseases/congenital/metabolism ; Mice ; Myocardium/*cytology/*metabolism ; Myocytes, Cardiac/cytology/metabolism ; Neuregulin-1/genetics/*metabolism ; *Organogenesis ; Receptor, Notch1/genetics/*metabolism ; Signal Transduction ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {In vertebrate hearts, the ventricular trabecular myocardium develops as a sponge-like network of cardiomyocytes that is critical for contraction and conduction, ventricular septation, papillary muscle formation and wall thickening through the process of compaction 1 . Defective trabeculation leads to embryonic lethality2-4 or non-compaction cardiomyopathy (NCC) 5 . There are divergent views on when and how trabeculation is initiated in different species. In zebrafish, trabecular cardiomyocytes extrude from compact myocardium 6 , whereas in chicks, chamber wall thickening occurs before overt trabeculation 7 . In mice, the onset of trabeculation has not been described, but is proposed to begin at embryonic day 9.0, when cardiomyocytes form radially oriented ribs 2 . Endocardium-myocardium communication is essential for trabeculation, and numerous signalling pathways have been identified, including Notch2,8 and Neuregulin (NRG) 4 . Late disruption of the Notch pathway causes NCC 5 . Whereas it has been shown that mutations in the extracellular matrix (ECM) genes Has2 and Vcan prevent the formation of trabeculae in mice9,10 and the matrix metalloprotease ADAMTS1 promotes trabecular termination 3 , the pathways involved in ECM dynamics and the molecular regulation of trabeculation during its early phases remain unexplored. Here we present a model of trabeculation in mice that integrates dynamic endocardial and myocardial cell behaviours and ECM remodelling, and reveal new epistatic relationships between the involved signalling pathways. NOTCH1 signalling promotes ECM degradation during the formation of endocardial projections that are critical for individualization of trabecular units, whereas NRG1 promotes myocardial ECM synthesis, which is necessary for trabecular rearrangement and growth. These systems interconnect through NRG1 control of Vegfa, but act antagonistically to establish trabecular architecture. These insights enabled the prediction of persistent ECM and cardiomyocyte growth in a mouse NCC model, providing new insights into the pathophysiology of congenital heart disease.}, } @article {pmid29743678, year = {2018}, author = {Ling, HQ and Ma, B and Shi, X and Liu, H and Dong, L and Sun, H and Cao, Y and Gao, Q and Zheng, S and Li, Y and Yu, Y and Du, H and Qi, M and Li, Y and Lu, H and Yu, H and Cui, Y and Wang, N and Chen, C and Wu, H and Zhao, Y and Zhang, J and Li, Y and Zhou, W and Zhang, B and Hu, W and van Eijk, MJT and Tang, J and Witsenboer, HMA and Zhao, S and Li, Z and Zhang, A and Wang, D and Liang, C}, title = {Genome sequence of the progenitor of wheat A subgenome Triticum urartu.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {424-428}, doi = {10.1038/s41586-018-0108-0}, pmid = {29743678}, issn = {1476-4687}, mesh = {Altitude ; Chromosomes, Artificial, Bacterial/genetics ; Chromosomes, Plant/genetics ; DNA Transposable Elements/genetics ; *Evolution, Molecular ; Genetic Variation ; Genome, Plant/*genetics ; Geographic Mapping ; Molecular Sequence Annotation ; *Phylogeny ; Plant Diseases/microbiology ; Sequence Analysis, DNA ; Synteny/genetics ; Triticum/*classification/*genetics ; }, abstract = {Triticum urartu (diploid, AA) is the progenitor of the A subgenome of tetraploid (Triticum turgidum, AABB) and hexaploid (Triticum aestivum, AABBDD) wheat1,2. Genomic studies of T. urartu have been useful for investigating the structure, function and evolution of polyploid wheat genomes. Here we report the generation of a high-quality genome sequence of T. urartu by combining bacterial artificial chromosome (BAC)-by-BAC sequencing, single molecule real-time whole-genome shotgun sequencing 3 , linked reads and optical mapping4,5. We assembled seven chromosome-scale pseudomolecules and identified protein-coding genes, and we suggest a model for the evolution of T. urartu chromosomes. Comparative analyses with genomes of other grasses showed gene loss and amplification in the numbers of transposable elements in the T. urartu genome. Population genomics analysis of 147 T. urartu accessions from across the Fertile Crescent showed clustering of three groups, with differences in altitude and biostress, such as powdery mildew disease. The T. urartu genome assembly provides a valuable resource for studying genetic variation in wheat and related grasses, and promises to facilitate the discovery of genes that could be useful for wheat improvement.}, } @article {pmid29743677, year = {2018}, author = {Tsunemoto, R and Lee, S and Szűcs, A and Chubukov, P and Sokolova, I and Blanchard, JW and Eade, KT and Bruggemann, J and Wu, C and Torkamani, A and Sanna, PP and Baldwin, KK}, title = {Diverse reprogramming codes for neuronal identity.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {375-380}, doi = {10.1038/s41586-018-0103-5}, pmid = {29743677}, issn = {1476-4687}, support = {R21 DA040458/DA/NIDA NIH HHS/United States ; DA031566/DA/NIDA NIH HHS/United States ; MH102698/MH/NIMH NIH HHS/United States ; DP1 AG055944/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Cellular Reprogramming/*genetics ; Fibroblasts/cytology/metabolism ; Gene Expression Profiling ; Gene Regulatory Networks ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Mice ; Neurons/*cytology/drug effects/*metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcription Factors/metabolism ; Transcriptome/genetics ; }, abstract = {The transcriptional programs that establish neuronal identity evolved to produce the rich diversity of neuronal cell types that arise sequentially during development. Remarkably, transient expression of certain transcription factors can also endow non-neural cells with neuronal properties. The relationship between reprogramming factors and the transcriptional networks that produce neuronal identity and diversity remains largely unknown. Here, from a screen of 598 pairs of transcription factors, we identify 76 pairs of transcription factors that induce mouse fibroblasts to differentiate into cells with neuronal features. By comparing the transcriptomes of these induced neuronal cells (iN cells) with those of endogenous neurons, we define a 'core' cell-autonomous neuronal signature. The iN cells also exhibit diversity; each transcription factor pair produces iN cells with unique transcriptional patterns that can predict their pharmacological responses. By linking distinct transcription factor input 'codes' to defined transcriptional outputs, this study delineates cell-autonomous features of neuronal identity and diversity and expands the reprogramming toolbox to facilitate engineering of induced neurons with desired patterns of gene expression and related functional properties.}, } @article {pmid29743676, year = {2018}, author = {Mohamed, MAA and Stepp, WL and Ökten, Z}, title = {Reconstitution reveals motor activation for intraflagellar transport.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {387-391}, pmid = {29743676}, issn = {1476-4687}, mesh = {Animals ; Biological Transport ; Caenorhabditis elegans/*metabolism ; Flagella/*metabolism ; Kinesin/metabolism ; *Movement ; Photobleaching ; }, abstract = {The human body represents a notable example of ciliary diversification. Extending from the surface of most cells, cilia accomplish a diverse set of tasks. Predictably, mutations in ciliary genes cause a wide range of human diseases such as male infertility and blindness. In Caenorhabditis elegans sensory cilia, this functional diversity appears to be traceable to the differential regulation of the kinesin-2-powered intraflagellar-transport (IFT) machinery. Here we reconstituted the first, to our knowledge, functional multi-component IFT complex that is deployed in the sensory cilia of C. elegans. Our bottom-up approach revealed the molecular basis of specific motor recruitment to the IFT trains. We identified the key component that incorporates homodimeric kinesin-2 into its physiologically relevant context, which in turn allosterically activates the motor for efficient transport. These results will enable the molecular delineation of IFT regulation, which has eluded understanding since its discovery more than two decades ago.}, } @article {pmid29743675, year = {2018}, author = {Damgaard, PB and Marchi, N and Rasmussen, S and Peyrot, M and Renaud, G and Korneliussen, T and Moreno-Mayar, JV and Pedersen, MW and Goldberg, A and Usmanova, E and Baimukhanov, N and Loman, V and Hedeager, L and Pedersen, AG and Nielsen, K and Afanasiev, G and Akmatov, K and Aldashev, A and Alpaslan, A and Baimbetov, G and Bazaliiskii, VI and Beisenov, A and Boldbaatar, B and Boldgiv, B and Dorzhu, C and Ellingvag, S and Erdenebaatar, D and Dajani, R and Dmitriev, E and Evdokimov, V and Frei, KM and Gromov, A and Goryachev, A and Hakonarson, H and Hegay, T and Khachatryan, Z and Khaskhanov, R and Kitov, E and Kolbina, A and Kubatbek, T and Kukushkin, A and Kukushkin, I and Lau, N and Margaryan, A and Merkyte, I and Mertz, IV and Mertz, VK and Mijiddorj, E and Moiyesev, V and Mukhtarova, G and Nurmukhanbetov, B and Orozbekova, Z and Panyushkina, I and Pieta, K and Smrčka, V and Shevnina, I and Logvin, A and Sjögren, KG and Štolcová, T and Taravella, AM and Tashbaeva, K and Tkachev, A and Tulegenov, T and Voyakin, D and Yepiskoposyan, L and Undrakhbold, S and Varfolomeev, V and Weber, A and Wilson Sayres, MA and Kradin, N and Allentoft, ME and Orlando, L and Nielsen, R and Sikora, M and Heyer, E and Kristiansen, K and Willerslev, E}, title = {137 ancient human genomes from across the Eurasian steppes.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {369-374}, doi = {10.1038/s41586-018-0094-2}, pmid = {29743675}, issn = {1476-4687}, mesh = {Asia/ethnology ; Asian Continental Ancestry Group/*genetics ; Europe/ethnology ; European Continental Ancestry Group/*genetics ; Farmers/history ; Genome, Human/*genetics ; *Grassland ; History, Ancient ; Human Migration/history ; Humans ; *Phylogeny ; }, abstract = {For thousands of years the Eurasian steppes have been a centre of human migrations and cultural change. Here we sequence the genomes of 137 ancient humans (about 1× average coverage), covering a period of 4,000 years, to understand the population history of the Eurasian steppes after the Bronze Age migrations. We find that the genetics of the Scythian groups that dominated the Eurasian steppes throughout the Iron Age were highly structured, with diverse origins comprising Late Bronze Age herders, European farmers and southern Siberian hunter-gatherers. Later, Scythians admixed with the eastern steppe nomads who formed the Xiongnu confederations, and moved westward in about the second or third century BC, forming the Hun traditions in the fourth-fifth century AD, and carrying with them plague that was basal to the Justinian plague. These nomads were further admixed with East Asian groups during several short-term khanates in the Medieval period. These historical events transformed the Eurasian steppes from being inhabited by Indo-European speakers of largely West Eurasian ancestry to the mostly Turkic-speaking groups of the present day, who are primarily of East Asian ancestry.}, } @article {pmid29743674, year = {2018}, author = {Kim, YK and Wang, X and Mondkar, P and Bukusoglu, E and Abbott, NL}, title = {Self-reporting and self-regulating liquid crystals.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {539-544}, doi = {10.1038/s41586-018-0098-y}, pmid = {29743674}, issn = {1476-4687}, mesh = {Drug Liberation/radiation effects ; Elasticity ; Electricity ; Escherichia coli/physiology ; Fingers/physiology ; Hot Temperature ; Humans ; Light ; Liquid Crystals/*chemistry/radiation effects ; Touch ; }, abstract = {Liquid crystals (LCs) are anisotropic fluids that combine the long-range order of crystals with the mobility of liquids1,2. This combination of properties has been widely used to create reconfigurable materials that optically report information about their environment, such as changes in electric fields (smart-phone displays) 3 , temperature (thermometers) 4 or mechanical shear 5 , and the arrival of chemical and biological stimuli (sensors)6,7. An unmet need exists, however, for responsive materials that not only report their environment but also transform it through self-regulated chemical interactions. Here we show that a range of stimuli can trigger pulsatile (transient) or continuous release of microcargo (aqueous microdroplets or solid microparticles and their chemical contents) that is trapped initially within LCs. The resulting LC materials self-report and self-regulate their chemical response to targeted physical, chemical and biological events in ways that can be preprogrammed through an interplay of elastic, electrical double-layer, buoyant and shear forces in diverse geometries (such as wells, films and emulsion droplets). These LC materials can carry out complex functions that go beyond the capabilities of conventional materials used for controlled microcargo release, such as optically reporting a stimulus (for example, mechanical shear stresses generated by motile bacteria) and then responding in a self-regulated manner via a feedback loop (for example, to release the minimum amount of biocidal agent required to cause bacterial cell death).}, } @article {pmid29743673, year = {2018}, author = {Mühlemann, B and Jones, TC and Damgaard, PB and Allentoft, ME and Shevnina, I and Logvin, A and Usmanova, E and Panyushkina, IP and Boldgiv, B and Bazartseren, T and Tashbaeva, K and Merz, V and Lau, N and Smrčka, V and Voyakin, D and Kitov, E and Epimakhov, A and Pokutta, D and Vicze, M and Price, TD and Moiseyev, V and Hansen, AJ and Orlando, L and Rasmussen, S and Sikora, M and Vinner, L and Osterhaus, ADME and Smith, DJ and Glebe, D and Fouchier, RAM and Drosten, C and Sjögren, KG and Kristiansen, K and Willerslev, E}, title = {Ancient hepatitis B viruses from the Bronze Age to the Medieval period.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {418-423}, doi = {10.1038/s41586-018-0097-z}, pmid = {29743673}, issn = {1476-4687}, mesh = {Africa ; Animals ; Asia ; Europe ; *Evolution, Molecular ; Genotype ; Hepatitis B/*virology ; Hepatitis B virus/classification/*genetics/*isolation & purification ; History, Ancient ; History, Medieval ; Hominidae/virology ; Human Migration/history ; Humans ; *Phylogeny ; Recombination, Genetic ; }, abstract = {Hepatitis B virus (HBV) is a major cause of human hepatitis. There is considerable uncertainty about the timescale of its evolution and its association with humans. Here we present 12 full or partial ancient HBV genomes that are between approximately 0.8 and 4.5 thousand years old. The ancient sequences group either within or in a sister relationship with extant human or other ape HBV clades. Generally, the genome properties follow those of modern HBV. The root of the HBV tree is projected to between 8.6 and 20.9 thousand years ago, and we estimate a substitution rate of 8.04 × 10-6-1.51 × 10-5 nucleotide substitutions per site per year. In several cases, the geographical locations of the ancient genotypes do not match present-day distributions. Genotypes that today are typical of Africa and Asia, and a subgenotype from India, are shown to have an early Eurasian presence. The geographical and temporal patterns that we observe in ancient and modern HBV genotypes are compatible with well-documented human migrations during the Bronze and Iron Ages1,2. We provide evidence for the creation of HBV genotype A via recombination, and for a long-term association of modern HBV genotypes with humans, including the discovery of a human genotype that is now extinct. These data expose a complexity of HBV evolution that is not evident when considering modern sequences alone.}, } @article {pmid29743672, year = {2018}, author = {Peng, C and Gathagan, RJ and Covell, DJ and Medellin, C and Stieber, A and Robinson, JL and Zhang, B and Pitkin, RM and Olufemi, MF and Luk, KC and Trojanowski, JQ and Lee, VM}, title = {Cellular milieu imparts distinct pathological α-synuclein strains in α-synucleinopathies.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {558-563}, pmid = {29743672}, issn = {1476-4687}, support = {P50 NS053488/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cytoplasm/chemistry/*metabolism/pathology ; Female ; Humans ; Lewy Bodies/chemistry/*metabolism/*pathology ; Lewy Body Disease/*metabolism/*pathology ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/chemistry/*metabolism/pathology ; Oligodendroglia/chemistry/metabolism/pathology ; Organ Specificity ; Protein Folding ; alpha-Synuclein/chemistry/*classification/*metabolism ; }, abstract = {In Lewy body diseases-including Parkinson's disease, without or with dementia, dementia with Lewy bodies, and Alzheimer's disease with Lewy body co-pathology 1 -α-synuclein (α-Syn) aggregates in neurons as Lewy bodies and Lewy neurites 2 . By contrast, in multiple system atrophy α-Syn accumulates mainly in oligodendrocytes as glial cytoplasmic inclusions (GCIs) 3 . Here we report that pathological α-Syn in GCIs and Lewy bodies (GCI-α-Syn and LB-α-Syn, respectively) is conformationally and biologically distinct. GCI-α-Syn forms structures that are more compact and it is about 1,000-fold more potent than LB-α-Syn in seeding α-Syn aggregation, consistent with the highly aggressive nature of multiple system atrophy. GCI-α-Syn and LB-α-Syn show no cell-type preference in seeding α-Syn pathology, which raises the question of why they demonstrate different cell-type distributions in Lewy body disease versus multiple system atrophy. We found that oligodendrocytes but not neurons transform misfolded α-Syn into a GCI-like strain, highlighting the fact that distinct α-Syn strains are generated by different intracellular milieus. Moreover, GCI-α-Syn maintains its high seeding activity when propagated in neurons. Thus, α-Syn strains are determined by both misfolded seeds and intracellular environments.}, } @article {pmid29743671, year = {2018}, author = {Shepherd, ES and DeLoache, WC and Pruss, KM and Whitaker, WR and Sonnenburg, JL}, title = {An exclusive metabolic niche enables strain engraftment in the gut microbiota.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {434-438}, pmid = {29743671}, issn = {1476-4687}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteroides/growth & development/isolation & purification/physiology ; Colon/*microbiology ; *Fecal Microbiota Transplantation ; Female ; Gastrointestinal Microbiome/*physiology ; Humans ; Male ; Mice ; Sepharose/analogs & derivatives/metabolism ; }, abstract = {The dense microbial ecosystem in the gut is intimately connected to numerous facets of human biology, and manipulation of the gut microbiota has broad implications for human health. In the absence of profound perturbation, the bacterial strains that reside within an individual are mostly stable over time 1 . By contrast, the fate of exogenous commensal and probiotic strains applied to an established microbiota is variable, generally unpredictable and greatly influenced by the background microbiota2,3. Therefore, analysis of the factors that govern strain engraftment and abundance is of critical importance to the emerging field of microbiome reprogramming. Here we generate an exclusive metabolic niche in mice via administration of a marine polysaccharide, porphyran, and an exogenous Bacteroides strain harbouring a rare gene cluster for porphyran utilization. Privileged nutrient access enables reliable engraftment of the exogenous strain at predictable abundances in mice harbouring diverse communities of gut microbes. This targeted dietary support is sufficient to overcome priority exclusion by an isogenic strain 4 , and enables strain replacement. We demonstrate transfer of the 60-kb porphyran utilization locus into a naive strain of Bacteroides, and show finely tuned control of strain abundance in the mouse gut across multiple orders of magnitude by varying porphyran dosage. Finally, we show that this system enables the introduction of a new strain into the colonic crypt ecosystem. These data highlight the influence of nutrient availability in shaping microbiota membership, expand the ability to perform a broad spectrum of investigations in the context of a complex microbiota, and have implications for cell-based therapeutic strategies in the gut.}, } @article {pmid29743670, year = {2018}, author = {Banino, A and Barry, C and Uria, B and Blundell, C and Lillicrap, T and Mirowski, P and Pritzel, A and Chadwick, MJ and Degris, T and Modayil, J and Wayne, G and Soyer, H and Viola, F and Zhang, B and Goroshin, R and Rabinowitz, N and Pascanu, R and Beattie, C and Petersen, S and Sadik, A and Gaffney, S and King, H and Kavukcuoglu, K and Hassabis, D and Hadsell, R and Kumaran, D}, title = {Vector-based navigation using grid-like representations in artificial agents.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {429-433}, doi = {10.1038/s41586-018-0102-6}, pmid = {29743670}, issn = {1476-4687}, mesh = {Animals ; Biomimetics/*methods ; Entorhinal Cortex/cytology/physiology ; Environment ; Grid Cells/physiology ; Humans ; *Machine Learning ; *Neural Networks (Computer) ; *Spatial Navigation ; }, abstract = {Deep neural networks have achieved impressive successes in fields ranging from object recognition to complex games such as Go1,2. Navigation, however, remains a substantial challenge for artificial agents, with deep neural networks trained by reinforcement learning3-5 failing to rival the proficiency of mammalian spatial behaviour, which is underpinned by grid cells in the entorhinal cortex 6 . Grid cells are thought to provide a multi-scale periodic representation that functions as a metric for coding space7,8 and is critical for integrating self-motion (path integration)6,7,9 and planning direct trajectories to goals (vector-based navigation)7,10,11. Here we set out to leverage the computational functions of grid cells to develop a deep reinforcement learning agent with mammal-like navigational abilities. We first trained a recurrent network to perform path integration, leading to the emergence of representations resembling grid cells, as well as other entorhinal cell types 12 . We then showed that this representation provided an effective basis for an agent to locate goals in challenging, unfamiliar, and changeable environments-optimizing the primary objective of navigation through deep reinforcement learning. The performance of agents endowed with grid-like representations surpassed that of an expert human and comparison agents, with the metric quantities necessary for vector-based navigation derived from grid-like units within the network. Furthermore, grid-like representations enabled agents to conduct shortcut behaviours reminiscent of those performed by mammals. Our findings show that emergent grid-like representations furnish agents with a Euclidean spatial metric and associated vector operations, providing a foundation for proficient navigation. As such, our results support neuroscientific theories that see grid cells as critical for vector-based navigation7,10,11, demonstrating that the latter can be combined with path-based strategies to support navigation in challenging environments.}, } @article {pmid29743650, year = {2018}, author = {Corbett, S and Courtiol, A and Lummaa, V and Moorad, J and Stearns, S}, title = {The transition to modernity and chronic disease: mismatch and natural selection.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {419-430}, doi = {10.1038/s41576-018-0012-3}, pmid = {29743650}, issn = {1471-0064}, abstract = {The Industrial Revolution and the accompanying nutritional, epidemiological and demographic transitions have profoundly changed human ecology and biology, leading to major shifts in life history traits, which include age and size at maturity, age-specific fertility and lifespan. Mismatch between past adaptations and the current environment means that gene variants linked to higher fitness in the past may now, through antagonistic pleiotropic effects, predispose post-transition populations to non-communicable diseases, such as Alzheimer disease, cancer and coronary artery disease. Increasing evidence suggests that the transition to modernity has also altered the direction and intensity of natural selection acting on many traits, with important implications for public and global health.}, } @article {pmid29743568, year = {2018}, author = {Pearce, DG and Bonneau, A}, title = {Publisher Correction: Trouble on the dating scene.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {1040}, doi = {10.1038/s41559-018-0566-7}, pmid = {29743568}, issn = {2397-334X}, abstract = {In the version of this News & Views originally published, the name Hoffmann was incorrectly spelt as Hoffman in two instances. This has been corrected.}, } @article {pmid29743352, year = {2018}, author = {de Barros Damgaard, P and Martiniano, R and Kamm, J and Moreno-Mayar, JV and Kroonen, G and Peyrot, M and Barjamovic, G and Rasmussen, S and Zacho, C and Baimukhanov, N and Zaibert, V and Merz, V and Biddanda, A and Merz, I and Loman, V and Evdokimov, V and Usmanova, E and Hemphill, B and Seguin-Orlando, A and Yediay, FE and Ullah, I and Sjögren, KG and Iversen, KH and Choin, J and de la Fuente, C and Ilardo, M and Schroeder, H and Moiseyev, V and Gromov, A and Polyakov, A and Omura, S and Senyurt, SY and Ahmad, H and McKenzie, C and Margaryan, A and Hameed, A and Samad, A and Gul, N and Khokhar, MH and Goriunova, OI and Bazaliiskii, VI and Novembre, J and Weber, AW and Orlando, L and Allentoft, ME and Nielsen, R and Kristiansen, K and Sikora, M and Outram, AK and Durbin, R and Willerslev, E}, title = {The first horse herders and the impact of early Bronze Age steppe expansions into Asia.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6396}, pages = {}, doi = {10.1126/science.aar7711}, pmid = {29743352}, issn = {1095-9203}, support = {T32 GM007197/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Asia ; Asian Continental Ancestry Group/*genetics ; Chromosomes, Human, Y/genetics ; DNA, Ancient ; DNA, Mitochondrial/genetics ; *Domestication ; Europe ; *Genetic Drift ; *Genome, Human ; Grassland ; History, Ancient ; *Horses ; Human Migration/*history ; Humans ; Language ; Whole Genome Sequencing ; }, abstract = {The Yamnaya expansions from the western steppe into Europe and Asia during the Early Bronze Age (~3000 BCE) are believed to have brought with them Indo-European languages and possibly horse husbandry. We analyzed 74 ancient whole-genome sequences from across Inner Asia and Anatolia and show that the Botai people associated with the earliest horse husbandry derived from a hunter-gatherer population deeply diverged from the Yamnaya. Our results also suggest distinct migrations bringing West Eurasian ancestry into South Asia before and after, but not at the time of, Yamnaya culture. We find no evidence of steppe ancestry in Bronze Age Anatolia from when Indo-European languages are attested there. Thus, in contrast to Europe, Early Bronze Age Yamnaya-related migrations had limited direct genetic impact in Asia.}, } @article {pmid29743190, year = {2018}, author = {Shen, X and Shen, S and Li, J and Hu, Q and Nie, L and Tu, C and Wang, X and Poulsen, DJ and Orsburn, BC and Wang, J and Qu, J}, title = {IonStar enables high-precision, low-missing-data proteomics quantification in large biological cohorts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4767-E4776}, pmid = {29743190}, issn = {1091-6490}, mesh = {Animals ; Biomarkers/*analysis ; Brain/drug effects/*metabolism ; Brain Injuries, Traumatic/drug therapy/*metabolism/pathology ; Central Nervous System Stimulants/pharmacology ; Male ; Methamphetamine/*pharmacology ; Proteome/*analysis ; Proteomics/*methods ; Rats ; Rats, Wistar ; Reproducibility of Results ; Tandem Mass Spectrometry ; }, abstract = {Reproducible quantification of large biological cohorts is critical for clinical/pharmaceutical proteomics yet remains challenging because most prevalent methods suffer from drastically declined commonly quantified proteins and substantially deteriorated quantitative quality as cohort size expands. MS2-based data-independent acquisition approaches represent tremendous advancements in reproducible protein measurement, but often with limited depth. We developed IonStar, an MS1-based quantitative approach enabling in-depth, high-quality quantification of large cohorts by combining efficient/reproducible experimental procedures with unique data-processing components, such as efficient 3D chromatographic alignment, sensitive and selective direct ion current extraction, and stringent postfeature generation quality control. Compared with several popular label-free methods, IonStar exhibited far lower missing data (0.1%), superior quantitative accuracy/precision [∼5% intragroup coefficient of variation (CV)], the widest protein abundance range, and the highest sensitivity/specificity for identifying protein changes (<5% false altered-protein discovery) in a benchmark sample set (n = 20). We demonstrated the usage of IonStar by a large-scale investigation of traumatic injuries and pharmacological treatments in rat brains (n = 100), quantifying >7,000 unique protein groups (>99.8% without missing data across the 100 samples) with a low false discovery rate (FDR), two or more unique peptides per protein, and high quantitative precision. IonStar represents a reliable and robust solution for precise and reproducible protein measurement in large cohorts.}, } @article {pmid29743103, year = {2018}, author = {Zaman, SB and Gupta, RD and Al Kibria, GM and Hossain, N and Bulbul, MMI and Hoque, DME}, title = {Husband's involvement with mother's awareness and knowledge of newborn danger signs in facility-based childbirth settings: a cross-sectional study from rural Bangladesh.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {286}, pmid = {29743103}, issn = {1756-0500}, mesh = {Adult ; Bangladesh ; Cross-Sectional Studies ; Delivery, Obstetric ; Female ; *Health Facilities ; *Health Knowledge, Attitudes, Practice ; Humans ; Infant, Newborn ; Male ; *Mothers ; *Parturition ; *Rural Population ; *Spouses ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to examine the association between husband involvement and maternal awareness and knowledge of newborn danger signs. This cross-sectional study was conducted in three rural hospitals of Bangladesh among the recently delivered women (RDW).

RESULTS: RDW were interviewed to determine their knowledge and understanding of seven key neonatal danger signs. About 51.4% of the respondents were able to identify at least one danger sign. 'Fever' was the most correctly identified (43.7%), and hypothermia was the least (26.1%) identified danger sign. The factors associated with RDW possessing knowledge of at least one neonatal danger sign were: secondary education (COR: 1.3, 95% CI 1.1-1.6), increased ANC visits (COR: 1.2, 95% CI 1.1-1.3), previous history of facility delivery (COR: 1.3, 95% CI 1.1-1.4), and husband involvement in the mother's facility delivery (COR: 1.3, 95% CI 1.1-1.5). RDW were more likely to recall at least one newborn danger sign (AOR: 1.2, 95% CI 1.1-1.4) when the husband was actively involved in his wife's antenatal, delivery and postnatal care. In conclusion, this study found that husband involvement was significantly associated with the maternal knowledge related to identification of neonatal danger signs.}, } @article {pmid29743093, year = {2018}, author = {Lumsden, AL and Ma, Y and Ashander, LM and Stempel, AJ and Keating, DJ and Smith, JR and Appukuttan, B}, title = {ICAM-1-related long non-coding RNA: promoter analysis and expression in human retinal endothelial cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {285}, pmid = {29743093}, issn = {1756-0500}, support = {APP1123684//National Health and Medical Research Council/ ; FT130101648//Australian Research Council/ ; }, mesh = {Alleles ; Binding Sites ; Endothelial Cells/*metabolism ; *Gene Expression Regulation ; Humans ; Intercellular Adhesion Molecule-1/*genetics/metabolism ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; *Promoter Regions, Genetic ; Protein Binding ; RNA, Long Noncoding/*genetics/metabolism ; Retina/*cytology ; Transcription Factors/metabolism ; }, abstract = {OBJECTIVE: Regulation of intercellular adhesion molecule (ICAM)-1 in retinal endothelial cells is a promising druggable target for retinal vascular diseases. The ICAM-1-related (ICR) long non-coding RNA stabilizes ICAM-1 transcript, increasing protein expression. However, studies of ICR involvement in disease have been limited as the promoter is uncharacterized. To address this issue, we undertook a comprehensive in silico analysis of the human ICR gene promoter region.

RESULTS: We used genomic evolutionary rate profiling to identify a 115 base pair (bp) sequence within 500 bp upstream of the transcription start site of the annotated human ICR gene that was conserved across 25 eutherian genomes. A second constrained sequence upstream of the orthologous mouse gene (68 bp; conserved across 27 Eutherian genomes including human) was also discovered. Searching these elements identified 33 matrices predictive of binding sites for transcription factors known to be responsive to a broad range of pathological stimuli, including hypoxia, and metabolic and inflammatory proteins. Five phenotype-associated single nucleotide polymorphisms (SNPs) in the immediate vicinity of these elements included four SNPs (i.e. rs2569693, rs281439, rs281440 and rs11575074) predicted to impact binding motifs of transcription factors, and thus the expression of ICR and ICAM-1 genes, with potential to influence disease susceptibility. We verified that human retinal endothelial cells expressed ICR, and observed induction of expression by tumor necrosis factor-α.}, } @article {pmid29743038, year = {2018}, author = {Jiang, SY and Sevugan, M and Ramachandran, S}, title = {Valine-glutamine (VQ) motif coding genes are ancient and non-plant-specific with comprehensive expression regulation by various biotic and abiotic stresses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {342}, pmid = {29743038}, issn = {1471-2164}, support = {NRF-CRP7-2010-02//National Research Foundation Singapore/ ; }, mesh = {*Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Bacteria ; Fungi ; *Gene Expression Regulation ; *Genome ; Glutamine/chemistry/metabolism ; Plants ; Proteins/*genetics/metabolism ; Sequence Homology ; *Stress, Physiological ; *Transcriptome ; Valine/chemistry/metabolism ; Viruses ; }, abstract = {BACKGROUND: Valine-glutamine (VQ) motif containing proteins play important roles in abiotic and biotic stress responses in plants. However, little is known about the origin and evolution as well as comprehensive expression regulation of the VQ gene family.

RESULTS: In this study, we systematically surveyed this gene family in 50 plant genomes from algae, moss, gymnosperm and angiosperm and explored their presence in other species from animals, bacteria, fungi and viruses. No VQs were detected in all tested algae genomes and all genomes from moss, gymnosperm and angiosperm encode varying numbers of VQs. Interestingly, some of fungi, lower animals and bacteria also encode single to a few VQs. Thus, they are not plant-specific and should be regarded as an ancient family. Their family expansion was mainly due to segmental duplication followed by tandem duplication and mobile elements. Limited contribution of gene conversion was detected to the family evolution. Generally, VQs were very much conserved in their motif coding region and were under purifying selection. However, positive selection was also observed during species divergence. Many VQs were up- or down-regulated by various abiotic / biotic stresses and phytohormones in rice and Arabidopsis. They were also co-expressed with some of other stress-related genes. All of the expression data suggest a comprehensive expression regulation of the VQ gene family.

CONCLUSIONS: We provide new insights into gene expansion, divergence, evolution and their expression regulation of this VQ family. VQs were detectable not only in plants but also in some of fungi, lower animals and bacteria, suggesting the evolutionary conservation and the ancient origin. Overall, VQs are non-plant-specific and play roles in abiotic / biotic responses or other biological processes through comprehensive expression regulation.}, } @article {pmid29743036, year = {2018}, author = {Cui, X and Cui, H and Liu, L and Zhao, G and Liu, R and Li, Q and Zheng, M and Wen, J}, title = {Decreased testosterone levels after caponization leads to abdominal fat deposition in chickens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {344}, pmid = {29743036}, issn = {1471-2164}, support = {No. 31372305//grants from the National Natural Science Funds of China/ ; ASTIP-IAS04, ASTIP-IAS18, ASTIP-IAS-TS-11//Agricultural Science and Technology Innovation Program/ ; }, mesh = {Abdominal Fat/metabolism/*physiopathology ; Androgens/*blood ; Animals ; Biomarkers/*metabolism ; Chickens ; Gene Expression Profiling ; Male ; Orchiectomy/*veterinary ; Signal Transduction ; Testosterone/*blood ; }, abstract = {BACKGROUND: Caponization results in reduced androgen levels, which leads to abdominal fat accumulation in capons. In this study, we sought to understand the molecular mechanisms behind this fat accumulation.

RESULTS: Abdominal fat (AF) content increased significantly (P < 0.05) and serum and AF testosterone levels decreased significantly (P < 0.05 or P < 0.01) after caponization. In AF tissue, 90 differentially expressed genes related to lipid metabolism were screened by gene expression profiling in caponized and sham-treated chickens. Among these, six representative genes were significantly up-regulated (APOA1, SCD, FABP7, RXRG, and FADS2) or down-regulated (FABP3) (P < 0.05 or P < 0.01) and were strongly associated with the PPAR pathway. In addition, cell junction pathways were also enriched. In vitro, Fat content was significantly lower in cells treated with testosterone compared with control cells (P < 0.01), and mRNA levels of RXRG, FABP7, and FABP3 changed accordingly, confirming the effect of testosterone on fat deposition.

CONCLUSIONS: The results of this study indicate that testosterone reduction likely regulates gene expression through PPAR and cell junction pathways resulting in increased fat accumulation. These results provide increase our understanding of the biological mechanisms by which caponization induces greater fat accumulation.}, } @article {pmid29743024, year = {2018}, author = {Szűcs, Z and Plaszkó, T and Cziáky, Z and Kiss-Szikszai, A and Emri, T and Bertóti, R and Sinka, LT and Vasas, G and Gonda, S}, title = {Endophytic fungi from the roots of horseradish (Armoracia rusticana) and their interactions with the defensive metabolites of the glucosinolate - myrosinase - isothiocyanate system.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {85}, pmid = {29743024}, issn = {1471-2229}, support = {PD 112374//Országos Tudományos Kutatási Alapprogramok/ ; 124339//Országos Tudományos Kutatási Alapprogramok/ ; EFOP-3.6.1-16-2016-00022//European Social Fund/ ; }, mesh = {Armoracia/metabolism/*microbiology ; Ascomycota/metabolism ; Endophytes/*metabolism ; Fusarium/metabolism ; Glucosinolates/*metabolism ; Glycoside Hydrolases/*metabolism ; Isothiocyanates/*metabolism ; Plant Roots/metabolism/*microbiology ; Soil Microbiology ; }, abstract = {BACKGROUND: The health of plants is heavily influenced by the intensively researched plant microbiome. The microbiome has to cope with the plant's defensive secondary metabolites to survive and develop, but studies that describe this interaction are rare. In the current study, we describe interactions of endophytic fungi with a widely researched chemical defense system, the glucosinolate - myrosinase - isothiocyanate system. The antifungal isothiocyanates are also of special interest because of their beneficial effects on human consumers.

RESULTS: Seven endophytic fungi were isolated from horseradish roots (Armoracia rusticana), from the genera Fusarium, Macrophomina, Setophoma, Paraphoma and Oidiodendron. LC-ESI-MS analysis of the horseradish extract incubated with these fungi showed that six of seven strains could decompose different classes of glucosinolates. Aliphatic, aromatic, thiomethylalkyl and indolic glucosinolates were decomposed by different strains at different rates. SPME-GC-MS measurements showed that two strains released significant amounts of allyl isothiocyanate into the surrounding air, but allyl nitrile was not detected. The LC-ESI-MS analysis of many strains' media showed the presence of allyl isothiocyanate - glutathione conjugate during the decomposition of sinigrin. Four endophytic strains also accepted sinigrin as the sole carbon source. Isothiocyanates inhibited the growth of fungi at various concentrations, phenylethyl isothiocyanate was more potent than allyl isothiocyanate (mean IC50 was 2.30-fold lower). As a control group, ten soil fungi from the same soil were used. They decomposed glucosinolates with lower overall efficiency: six of ten strains had insignificant or weak activities and only three could use sinigrin as a carbon source. The soil fungi also showed lower AITC tolerance in the growth inhibition assay: the median IC50 values were 0.1925 mM for endophytes and 0.0899 mM for soil fungi.

CONCLUSIONS: The host's glucosinolates can be used by the tested endophytic fungi as nutrients or to gain competitive advantage over less tolerant species. These activities were much less apparent among the soil fungi. This suggests that the endophytes show adaptation to the host plant's secondary metabolites and that host metabolite specific activities are enriched in the root microbiome. The results present background mechanisms enabling an understanding of how plants shape their microbiome.}, } @article {pmid29743016, year = {2018}, author = {Liu, X and He, Z and Yin, Y and Xu, X and Wu, W and Li, L}, title = {Transcriptome sequencing and analysis during seed growth and development in Euryale ferox Salisb.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {343}, pmid = {29743016}, issn = {1471-2164}, support = {CARS-24//China Agriculture Research System/ ; }, mesh = {Computational Biology ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Plant ; High-Throughput Nucleotide Sequencing ; Molecular Sequence Annotation ; Nymphaeaceae/*genetics/growth & development ; Plant Proteins/*genetics ; Seeds/*genetics/growth & development ; *Transcriptome ; }, abstract = {BACKGROUND: Euryale ferox Salisb., an annual aquatic plant, is the only species in the genus Euryale in the Nymphaeaceae. Seeds of E. ferox are a nutritious food and also used in traditional Chinese medicine (Qian Shi in Mandarin). The molecular events that occurred during seed development in E. ferox have not yet been characterized. In this study, we performed transcriptomic analysis of four developmental stages (T1, T2, T3, and T4) in E. ferox seeds with three biological replicates per developmental stage to understand the physiological and biochemical processes during E. ferox seeds development.

RESULTS: 313,844,425 clean reads were assembled into 160,107 transcripts and 85,006 unigenes with N50 lengths of 2052 bp and 1399 bp, respectively. The unigenes were annotated using five public databases (NR, COG, Swiss-Prot, KEGG, and GO). In the KEGG database, all of the unigenes were assigned to 127 pathways, of which phenylpropanoid biosynthesis was associated with the synthesis of secondary metabolites during E. ferox seed growth and development. Phenylalanine ammonia-lyase (PAL) as the first key enzyme catalyzed the conversion of phenylalanine to trans-cinnamic acid, then was related to the synthesis of flavonoids, lignins and alkaloid. The expression of PAL1 reached its peak at T3 stage, followed by a slight decrease at T4 stage. Cytochrome P450 (P450), encoded by CYP84A1 (which also called ferulate-5-hydroxylase (F5H) in Arabidopsis), was mainly involved in the biosynthesis of lignins.

CONCLUSIONS: Our study provides a transcriptomic analysis to better understand the morphological changes and the accumulation of medicinal components during E. ferox seed development. The increasing expression of PAL and P450 encoded genes in phenylpropanoid biosynthesis may promote the maturation of E. ferox seed including size, color, hardness and accumulation of medicinal components.}, } @article {pmid29743014, year = {2018}, author = {Song, X and Ma, X and Li, C and Hu, J and Yang, Q and Wang, T and Wang, L and Wang, J and Guo, D and Ge, W and Wang, Z and Li, M and Wang, Q and Ren, T and Feng, S and Wang, L and Zhang, W and Wang, X}, title = {Comprehensive analyses of the BES1 gene family in Brassica napus and examination of their evolutionary pattern in representative species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {346}, pmid = {29743014}, issn = {1471-2164}, support = {C2017209103//Natural Science Foundation of Hebei Province/ ; E2013100003//China-Hebei 100 Scholars Supporting Project/ ; }, mesh = {Arabidopsis/genetics ; Arabidopsis Proteins/genetics ; Brassica napus/*classification/*genetics ; Chromosome Mapping ; Chromosomes, Plant ; *Evolution, Molecular ; Gene Duplication ; *Genes, Plant ; *Genome, Plant ; *Multigene Family ; Phylogeny ; }, abstract = {BACKGROUND: The BES1 gene family, an important class of plant-specific transcription factors, play key roles in the BR signal pathway in plants, regulating various development processes. Until now, there has been no comprehensive analysis of the BES1 gene family in Brassica napus, and a cross-genome exploration of their origin, copy number changes, and functional innovation in plants was also not available.

RESULTS: We identified 28 BES1 genes in B. napus from its two subgenomes (AA and CC). We found that 71.43% of them were duplicated in the tetraploidization, and their gene expression showed a prominent subgenome bias in the roots. Additionally, we identified 104 BES1 genes in another 18 representative angiosperms and performed a comparative analysis with B. napus, including evolutionary trajectory, gene duplication, positive selection, and expression pattern. Exploiting the available genome datasets, we performed a large-scale analysis across plants and algae suggested that the BES1 gene family could have originated from group F, expanding to form other groups (A to E) by duplicating or alternatively deleting some domains. We detected an additional domain containing M4 to M8 in exclusively groups F1 and F2. We found evidence that whole-genome duplication (WGD) contributed the most to the expansion of this gene family among examined dicots, while dispersed duplication contributed the most to expansion in certain monocots. Moreover, we inferred that positive selection might have occurred on major phylogenetic nodes during the evolution of plants.

CONCLUSIONS: Grossly, a cross-genome comparative analysis of the BES1 genes in B. napus and other species sheds light on understanding its copy number expansion, natural selection, and functional innovation.}, } @article {pmid29743013, year = {2018}, author = {Zhang, B and Liu, J and Yang, ZE and Chen, EY and Zhang, CJ and Zhang, XY and Li, FG}, title = {Genome-wide analysis of GRAS transcription factor gene family in Gossypium hirsutum L.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {348}, pmid = {29743013}, issn = {1471-2164}, support = {31621005//the National Science Foundation/ ; 31501346//the National Science Foundation/ ; 2016TFD0101006//National key Research and Development Program/ ; }, mesh = {Chromosome Mapping ; *Chromosomes, Plant ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Genome, Plant ; Gossypium/*genetics ; Multigene Family ; Phylogeny ; Plant Proteins/*genetics ; Stress, Physiological ; Transcription Factors/*genetics ; }, abstract = {BACKGROUND: Cotton is a major fiber and oil crop worldwide. Cotton production, however, is often threatened by abiotic environmental stresses. GRAS family proteins are among the most abundant transcription factors in plants and play important roles in regulating root and shoot development, which can improve plant resistance to abiotic stresses. However, few studies on the GRAS family have been conducted in cotton. Recently, the G. hirsutum genome sequences have been released, which provide us an opportunity to analyze the GRAS family in G. hirsutum.

RESULTS: In total, 150 GRAS proteins from G. hirsutum were identified. Phylogenetic analysis showed that these GRAS protins could be classified into 14 subfamilies including SCR, DLT, OS19, LAS, SCL4/7, OS4, OS43, DELLA, PAT1, SHR, HAM, SCL3, LISCL and G_GRAS. The gene structure and motif distribution analysis of the GRAS members in G. hirsutum revealed that many genes of the SHR subfamily have more than one intron, which maybe a kind of form in the evolution of plant by obtaining or losing introns. Chromosomal location and duplication analysis revealed that segment and tandem duplication maybe the reasons of the expension of the GRAS family in cotton. Gene expression analysis confirmed the expression level of GRAS members were up-regulated under different abiotic stresses, suggesting that their possible roles in response to stresses. What's more, higher expression level in root, stem, leaf and pistil also indicated these genes may have effect on the development and breeding of cotton.

CONCLUSIONS: This study firstly shows the comprehensive analysis of GRAS members in G. hirsutum. Our results provide important information about GRAS family and a framework for stress-resistant breeding in G. hirsutum.}, } @article {pmid29743012, year = {2018}, author = {Nielsen, ES and Henriques, R and Toonen, RJ and Knapp, ISS and Guo, B and von der Heyden, S}, title = {Complex signatures of genomic variation of two non-model marine species in a homogeneous environment.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {347}, pmid = {29743012}, issn = {1471-2164}, support = {92788//National Research Foundation/ ; 1416889//National Science Foundation/ ; }, mesh = {Animals ; *Biological Evolution ; Gastropoda/*genetics ; *Genetic Variation ; *Genetics, Population ; Phylogeography ; Sea Urchins/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: Genomic tools are increasingly being used on non-model organisms to provide insights into population structure and variability, including signals of selection. However, most studies are carried out in regions with distinct environmental gradients or across large geographical areas, in which local adaptation is expected to occur. Therefore, the focus of this study is to characterize genomic variation and selective signals over short geographic areas within a largely homogeneous region. To assess adaptive signals between microhabitats within the rocky shore, we compared genomic variation between the Cape urchin (Parechinus angulosus), which is a low to mid-shore species, and the Granular limpet (Scutellastra granularis), a high shore specialist.

RESULTS: Using pooled restriction site associated DNA (RAD) sequencing, we described patterns of genomic variation and identified outlier loci in both species. We found relatively low numbers of outlier SNPs within each species, and identified outlier genes associated with different selective pressures than those previously identified in studies conducted over larger environmental gradients. The number of population-specific outlier loci differed between species, likely owing to differential selective pressures within the intertidal environment. Interestingly, the outlier loci were highly differentiated within the two northernmost populations for both species, suggesting that unique evolutionary forces are acting on marine invertebrates within this region.

CONCLUSIONS: Our study provides a background for comparative genomic studies focused on non-model species, as well as a baseline for the adaptive potential of marine invertebrates along the South African west coast. We also discuss the caveats associated with Pool-seq and potential biases of sequencing coverage on downstream genomic metrics. The findings provide evidence of species-specific selective pressures within a homogeneous environment, and suggest that selective forces acting on small scales are just as crucial to acknowledge as those acting on larger scales. As a whole, our findings imply that future population genomic studies should expand from focusing on model organisms and/or studying heterogeneous regions to better understand the evolutionary processes shaping current and future biodiversity patterns, particularly when used in a comparative phylogeographic context.}, } @article {pmid29743010, year = {2018}, author = {Kang, CP and Tu, HC and Fu, TF and Wu, JM and Chu, PH and Chang, DT}, title = {An automatic method to calculate heart rate from zebrafish larval cardiac videos.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {169}, pmid = {29743010}, issn = {1471-2105}, abstract = {BACKGROUND: Zebrafish is a widely used model organism for studying heart development and cardiac-related pathogenesis. With the ability of surviving without a functional circulation at larval stages, strong genetic similarity between zebrafish and mammals, prolific reproduction and optically transparent embryos, zebrafish is powerful in modeling mammalian cardiac physiology and pathology as well as in large-scale high throughput screening. However, an economical and convenient tool for rapid evaluation of fish cardiac function is still in need. There have been several image analysis methods to assess cardiac functions in zebrafish embryos/larvae, but they are still improvable to reduce manual intervention in the entire process. This work developed a fully automatic method to calculate heart rate, an important parameter to analyze cardiac function, from videos. It contains several filters to identify the heart region, to reduce video noise and to calculate heart rates.

RESULTS: The proposed method was evaluated with 32 zebrafish larval cardiac videos that were recording at three-day post-fertilization. The heart rate measured by the proposed method was comparable to that determined by manual counting. The experimental results show that the proposed method does not lose accuracy while largely reducing the labor cost and uncertainty of manual counting.

CONCLUSIONS: With the proposed method, researchers do not have to manually select a region of interest before analyzing videos. Moreover, filters designed to reduce video noise can alleviate background fluctuations during the video recording stage (e.g. shifting), which makes recorders generate usable videos easily and therefore reduce manual efforts while recording.}, } @article {pmid29743009, year = {2018}, author = {Burkholder, AB and Lujan, SA and Lavender, CA and Grimm, SA and Kunkel, TA and Fargo, DC}, title = {Muver, a computational framework for accurately calling accumulated mutations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {345}, pmid = {29743009}, issn = {1471-2164}, support = {Z01 ES065070/ES/NIEHS NIH HHS/United States ; Z01 ES103312//National Institute of Environmental Health Sciences/ ; Z01 ES065070//National Institute of Environmental Health Sciences/ ; }, mesh = {Computational Biology ; Fathers ; *Genome, Fungal ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; *Mutation Accumulation ; Mutation Rate ; Reference Standards ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*genetics ; Sequence Analysis, DNA/*methods ; *Software ; }, abstract = {BACKGROUND: Identification of mutations from next-generation sequencing data typically requires a balance between sensitivity and accuracy. This is particularly true of DNA insertions and deletions (indels), that can impart significant phenotypic consequences on cells but are harder to call than substitution mutations from whole genome mutation accumulation experiments. To overcome these difficulties, we present muver, a computational framework that integrates established bioinformatics tools with novel analytical methods to generate mutation calls with the extremely low false positive rates and high sensitivity required for accurate mutation rate determination and comparison.

RESULTS: Muver uses statistical comparison of ancestral and descendant allelic frequencies to identify variant loci and assigns genotypes with models that include per-sample assessments of sequencing errors by mutation type and repeat context. Muver identifies maximally parsimonious mutation pathways that connect these genotypes, differentiating potential allelic conversion events and delineating ambiguities in mutation location, type, and size. Benchmarking with a human gold standard father-son pair demonstrates muver's sensitivity and low false positive rates. In DNA mismatch repair (MMR) deficient Saccharomyces cerevisiae, muver detects multi-base deletions in homopolymers longer than the replicative polymerase footprint at rates greater than predicted for sequential single-base deletions, implying a novel multi-repeat-unit slippage mechanism.

CONCLUSIONS: Benchmarking results demonstrate the high accuracy and sensitivity achieved with muver, particularly for indels, relative to available tools. Applied to an MMR-deficient Saccharomyces cerevisiae system, muver mutation calls facilitate mechanistic insights into DNA replication fidelity.}, } @article {pmid29743008, year = {2018}, author = {Abdali, N and Younas, F and Mafakheri, S and Pothula, KR and Kleinekathöfer, U and Tauch, A and Benz, R}, title = {Identification and characterization of smallest pore-forming protein in the cell wall of pathogenic Corynebacterium urealyticum DSM 7109.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {3}, pmid = {29743008}, issn = {1471-2091}, support = {BE 865/16//Deutsche Forschungsgemeinschaft/International ; 115525//FP7 Ideas: European Research Council/International ; }, mesh = {Amino Acid Sequence ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/chemistry/genetics/*metabolism ; Cell Wall/*metabolism ; Corynebacterium/*metabolism/pathogenicity ; Electrophoresis, Polyacrylamide Gel ; Humans ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers ; Molecular Dynamics Simulation ; Porins/chemistry/genetics/*metabolism ; Protein Structure, Secondary ; Sequence Homology, Amino Acid ; Urinary Tract Infections/drug therapy/microbiology ; }, abstract = {BACKGROUND: Corynebacterium urealyticum, a pathogenic, multidrug resistant member of the mycolata, is known as causative agent of urinary tract infections although it is a bacterium of the skin flora. This pathogenic bacterium shares with the mycolata the property of having an unusual cell envelope composition and architecture, typical for the genus Corynebacterium. The cell wall of members of the mycolata contains channel-forming proteins for the uptake of solutes.

RESULTS: In this study, we provide novel information on the identification and characterization of a pore-forming protein in the cell wall of C. urealyticum DSM 7109. Detergent extracts of whole C. urealyticum cultures formed in lipid bilayer membranes slightly cation-selective pores with a single-channel conductance of 1.75 nS in 1 M KCl. Experiments with different salts and non-electrolytes suggested that the cell wall pore of C. urealyticum is wide and water-filled and has a diameter of about 1.8 nm. Molecular modelling and dynamics has been performed to obtain a model of the pore. For the search of the gene coding for the cell wall pore of C. urealyticum we looked in the known genome of C. urealyticum for a similar chromosomal localization of the porin gene to known porH and porA genes of other Corynebacterium strains. Three genes are located between the genes coding for GroEL2 and polyphosphate kinase (PKK2). Two of the genes (cur_1714 and cur_1715) were expressed in different constructs in C. glutamicum ΔporAΔporH and in porin-deficient BL21 DE3 Omp8 E. coli strains. The results suggested that the gene cur_1714 codes alone for the cell wall channel. The cell wall porin of C. urealyticum termed PorACur was purified to homogeneity using different biochemical methods and had an apparent molecular mass of about 4 kDa on tricine-containing sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE).

CONCLUSIONS: Biophysical characterization of the purified protein (PorACur) suggested indeed that cur_1714 is the gene coding for the pore-forming protein in C. urealyticum because the protein formed in lipid bilayer experiments the same pores as the detergent extract of whole cells. The study is the first report of a cell wall channel in the pathogenic C. urealyticum.}, } @article {pmid29742313, year = {2018}, author = {Forthman, M and Weirauch, C}, title = {Phylogenetic comparative analysis supports aposematic colouration-body size association in millipede assassins (Hemiptera: Reduviidae: Ectrichodiinae).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {1071-1078}, doi = {10.1111/jeb.13288}, pmid = {29742313}, issn = {1420-9101}, abstract = {The diversity of colour patterns and its importance in interactions with the environment make colouration in animals an intriguing research focus. Aposematic colouration is positively correlated with body size in certain groups of animals, suggesting that warning colours are more effective or that crypsis is harder to achieve in larger animals. Surprisingly, this relationship has not been recovered in studies investigating insects, which may have been confounded by a focus on aposematic taxa that are also gregarious. Millipede assassin bugs (Hemiptera: Reduviidae: Ectrichodiinae) comprise species with cryptic and aposematic colour patterns across a range of body sizes, are typically solitary as adults and are thus an excellent model for investigating a possible association between colouration and body size. Here, we use a comprehensive phylogeny for Ectrichodiinae, ancestral state reconstruction of colouration, and phylogenetic comparative methods to test for a colouration-body size association. The ancestor of Ectrichodiinae is reconstructed as cryptically coloured, with multiple subsequent transitions between aposematic and cryptic colouration. Aposematic colouration is positively associated with male body length and supports the hypothesis that selection on Ectrichodiinae body size may influence evolutionary transitions between aposematic and cryptic colouration or alternatively that selection for aposematic colouration influences body size evolution.}, } @article {pmid29741625, year = {2018}, author = {White, MF and Allers, T}, title = {DNA repair in the archaea-an emerging picture.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {514-526}, doi = {10.1093/femsre/fuy020}, pmid = {29741625}, issn = {1574-6976}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Archaea/*genetics ; *Biological Evolution ; DNA Repair/*physiology ; DNA, Archaeal/*genetics ; }, abstract = {There has long been a fascination in the DNA repair pathways of archaea, for two main reasons. Firstly, many archaea inhabit extreme environments where the rate of physical damage to DNA is accelerated. These archaea might reasonably be expected to have particularly robust or novel DNA repair pathways to cope with this. Secondly, the archaea have long been understood to be a lineage distinct from the bacteria, and to share a close relationship with the eukarya, particularly in their information processing systems. Recent discoveries suggest the eukarya arose from within the archaeal domain, and in particular from lineages related to the TACK superphylum and Lokiarchaea. Thus, archaeal DNA repair proteins and pathways can represent a useful model system. This review focuses on recent advances in our understanding of archaeal DNA repair processes including base excision repair, nucleotide excision repair, mismatch repair and double-strand break repair. These advances are discussed in the context of the emerging picture of the evolution and relationship of the three domains of life.}, } @article {pmid29741624, year = {2018}, author = {Esquivel-Elizondo, S and Maldonado, J and Krajmalnik-Brown, R}, title = {Anaerobic carbon monoxide metabolism by Pleomorphomonas carboxyditropha sp. nov., a new mesophilic hydrogenogenic carboxydotroph.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy056}, pmid = {29741624}, issn = {1574-6941}, abstract = {Carbon monoxide (CO)-metabolism and phenotypic and phylogenetic characterization of a novel anaerobic, mesophilic and hydrogenogenic carboxydotroph are reported. Strain SVCO-16 was isolated from anaerobic sludge and grows autotrophically and mixotrophically with CO. The genes cooS and cooF, coding for a CO dehydrogenase complex, and genes similar to hycE2, encoding a CO-induced hydrogenase, were present in its genome. The isolate produces H2 and CO2 from CO, and acetate and formate from organic substrates. Based on the 16S rRNA sequence, it is an Alphaproteobacterium most closely related to the genus Pleomorphomonas (98.9%-99.2% sequence identity). Comparison with other previously characterized Pleomorphomonas showed that P. diazotrophica and P. oryzae do not metabolize CO, and P. diazotrophica does not grow anaerobically with organic substrates. Average nucleotide identity values between strain SVCO-16 and P. diazotrophica, P. oryzae or P. koreensis were 86.66 ± 0.21%. These values are below the boundary to define species (95%-96%). Digital DNA-DNA hybridization estimates between strain SVCO-16 and reference strains were also below the 70% threshold for species delineation: 29.1%-34.5%. Based on the differences in CO metabolism, genome analyses and cellular fatty acid composition, the isolate should be classified into the genus Pleomorphomonas as a representative of a novel species, Pleomorphomonas carboxyditropha. The type strain of Pleomorphomonas carboxyditropha is SVCO-16T (strain deposit numbers, DSM 106132T and TSD-119T).}, } @article {pmid29741475, year = {2018}, author = {Thompson, F and Gomez-Gil, B}, title = {International Committee on Systematics of Prokaryotes Subcommittee on the taxonomy of Aeromonadaceae, Vibrionaceae and related organisms Minutes of the meeting, 13 November 2017, Chicago, USA.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2111-2112}, doi = {10.1099/ijsem.0.002815}, pmid = {29741475}, issn = {1466-5034}, } @article {pmid29741474, year = {2018}, author = {López, MM and Lopez-Soriano, P and Garita-Cambronero, J and Beltrán, C and Taghouti, G and Portier, P and Cubero, J and Fischer-Le Saux, M and Marco-Noales, E}, title = {Xanthomonas prunicola sp. nov., a novel pathogen that affects nectarine (Prunus persica var. nectarina) trees.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1857-1866}, doi = {10.1099/ijsem.0.002743}, pmid = {29741474}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fruit/microbiology ; Multilocus Sequence Typing ; *Phylogeny ; Pigmentation ; Plant Diseases/*microbiology ; Plant Leaves/microbiology ; Prunus persica/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spain ; Trees ; Xanthomonas/*classification/isolation & purification/pathogenicity ; }, abstract = {Three isolates obtained from symptomatic nectarine trees (Prunus persica var. nectarina) cultivated in Murcia, Spain, which showed yellow and mucoid colonies similar to Xanthomonas arboricola pv. pruni, were negative after serological and real-time PCR analyses for this pathogen. For that reason, these isolates were characterized following a polyphasic approach that included both phenotypic and genomic methods. By sequence analysis of the 16S rRNA gene, these novel strains were identified as members of the genus Xanthomonas, and by multilocus sequence analysis (MLSA) they were clustered together in a distinct group that showed similarity values below 95 % with the rest of the species of this genus. Whole-genome comparisons of the average nucleotide identity (ANI) of genomes of the strains showed less than 91 % average nucleotide identity with all other species of the genus Xanthomonas. Additionally, phenotypic characterization based on API 20 NE, API 50 CH and BIOLOG tests differentiated the strains from the species of the genus Xanthomonas described previously. Moreover, the three strains were confirmed to be pathogenic on peach (Prunus persica), causing necrotic lesions on leaves. On the basis of these results, the novel strains represent a novel species of the genus Xanthomonas, for which the name Xanthomonas prunicola is proposed. The type strain is CFBP 8353 (=CECT 9404=IVIA 3287.1).}, } @article {pmid29741268, year = {2018}, author = {Yeh, DJ and Boughman, JW and Saetre, GP and Servedio, MR}, title = {The evolution of sexual imprinting through reinforcement.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13500}, pmid = {29741268}, issn = {1558-5646}, abstract = {Reinforcement is the process whereby assortative mating evolves due to selection against costly hybridization. Sexual imprinting could evolve as a mechanism of reinforcement, decreasing hybridization, or it could potentially increase hybridization in genetically purebred offspring of heterospecific social pairs. We use deterministic population genetic simulations to explore conditions under which sexual imprinting can evolve through reinforcement. We demonstrate that a sexual imprinting component of female preference can evolve as a one-allele assortative mating mechanism by reducing the risk of hybridization, and is generally effective at causing trait divergence. However, imprinting often evolves to be a component rather than the sole determinant of female preference. The evolution of imprinting has the unexpected side effect of homogenizing existing innate preference, because the imprinted preference neutralizes any innate preference. We also find that the weight of the imprinting component may evolve to a lower value when migration and divergent selection are strong and the cost of hybridization is low; these conditions render hybridization adaptive for immigrant females because they can acquire locally adaptive genes by mating with local males. Together, these results suggest that sexual imprinting can itself evolve as part of the speciation process, and in doing so has the capacity to promote or retard divergence through complex interactions.}, } @article {pmid29741266, year = {2018}, author = {Lanzas, P and Perfectti, F and Garrido-Ramos, MA and Ruíz-Rejón, C and González-Sánchez, M and Puertas, M and Camacho, JPM}, title = {Long-term monitoring of B-chromosome invasion and neutralization in a population of Prospero autumnale (Asparagaceae).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1216-1224}, doi = {10.1111/evo.13501}, pmid = {29741266}, issn = {1558-5646}, abstract = {B chromosomes have been reported in about 15% of eukaryotes, but long-term dynamics of B chromosomes in a single natural population has rarely been analyzed. Prospero autumnale plants collected in 1981 and 1983 at Cuesta de La Palma population had shown the presence of B chromosomes. We analyze here seven additional samples collected between 1987 and 2015, and show that B frequency increased significantly during the 1980s and showed minor fluctuations between 2005 and 2015. A mother-offspring analysis of B chromosome transmission, at population level, showed significant drive on the male side (kB = 0.65) and significant drag on the female side (kB = 0.33), with average B transmission rate being very close to the Mendelian rate (0.5). No significant effects of B chromosomes were observed on a number of vigor and fertility-related traits. Within a parasite/host framework, these results suggest that B chromosomes' drive on the male side is the main pathway for B chromosome invasion, whereas B chromosome drag on the female side might be the main manifestation of host genome resistance in this species. Prospero autumnale thus illuminates a novel evolutionary pathway for B chromosome neutralization by means of a decrease in B transmission through the nondriving sex.}, } @article {pmid29741234, year = {2018}, author = {Hämälä, T and Mattila, TM and Savolainen, O}, title = {Local adaptation and ecological differentiation under selection, migration, and drift in Arabidopsis lyrata.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13502}, pmid = {29741234}, issn = {1558-5646}, abstract = {How the balance between selection, migration, and drift influences the evolution of local adaptation has been under intense theoretical scrutiny. Yet, empirical studies that relate estimates of local adaptation to quantification of gene flow and effective population sizes have been rare. Here, we conducted a reciprocal transplant trial, a common garden trial, and a whole-genome-based demography analysis to examine these effects among Arabidopsis lyrata populations from two altitudinal gradients in Norway. Demography simulations indicated that populations within the two gradients are connected by gene flow (0.1 < 4Ne m < 11) and have small effective population sizes (Ne < 6000), suggesting that both migration and drift can counteract local selection. However, the three-year field experiments showed evidence of local adaptation at the level of hierarchical multiyear fitness, attesting to the strength of differential selection. In the lowland habitat, local superiority was associated with greater fecundity, while viability accounted for fitness differences in the alpine habitat. We also demonstrate that flowering time differentiation has contributed to adaptive divergence between these locally adapted populations. Our results show that despite the estimated potential of gene flow and drift to hinder differentiation, selection among these A. lyrata populations has resulted in local adaptation.}, } @article {pmid29740144, year = {2018}, author = {Gibney, E}, title = {Universe's coolest lab set to open up quantum world.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {151-152}, doi = {10.1038/d41586-018-05111-2}, pmid = {29740144}, issn = {1476-4687}, } @article {pmid29740143, year = {2018}, author = {Ledford, H}, title = {Cancer-killing viruses show promise - and draw billion-dollar investment.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {150-151}, doi = {10.1038/d41586-018-05104-1}, pmid = {29740143}, issn = {1476-4687}, mesh = {Humans ; *Investments ; *Neoplasms ; *Oncolytic Viruses ; }, } @article {pmid29740142, year = {2018}, author = {Sohn, E}, title = {How to handle the dark days of depression.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {267-269}, doi = {10.1038/d41586-018-05088-y}, pmid = {29740142}, issn = {1476-4687}, } @article {pmid29740141, year = {2018}, author = {Reay, D}, title = {I'd whisper to my student self: you are not alone.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {160-161}, doi = {10.1038/d41586-018-05080-6}, pmid = {29740141}, issn = {1476-4687}, mesh = {Animals ; Anxiety/psychology ; Depression/*psychology ; *Education, Graduate ; Expeditions ; Fear/psychology ; Humans ; Male ; Mentors/*psychology ; Research ; Ships ; Social Stigma ; Students/*psychology ; Trust/psychology ; }, } @article {pmid29740138, year = {2018}, author = {Niehaus, AC}, title = {Write fiction to discover something new in your research.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {269}, doi = {10.1038/d41586-018-05089-x}, pmid = {29740138}, issn = {1476-4687}, } @article {pmid29740137, year = {2018}, author = {Zheng, X}, title = {Weak charge of the proton measured.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {171-172}, doi = {10.1038/d41586-018-05037-9}, pmid = {29740137}, issn = {1476-4687}, mesh = {*Elementary Particles ; Nuclear Physics ; *Protons ; }, } @article {pmid29740135, year = {2018}, author = {Castelvecchi, D}, title = {Particle physicists turn to AI to cope with CERN's collision deluge.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {147-148}, doi = {10.1038/d41586-018-05084-2}, pmid = {29740135}, issn = {1476-4687}, } @article {pmid29740134, year = {2018}, author = {Vesper, I}, title = {€100-billion budget proposed for Europe's next big research programme.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {150}, doi = {10.1038/d41586-018-05105-0}, pmid = {29740134}, issn = {1476-4687}, mesh = {Budgets/*legislation & jurisprudence ; Europe ; European Union/*economics ; Research/*economics/*organization & administration/trends ; Research Support as Topic/*economics/*legislation & jurisprudence/trends ; }, } @article {pmid29740133, year = {2018}, author = {Guglielmi, G}, title = {Yellowstone's grizzlies under threat from controversial hunting proposal.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {148-149}, doi = {10.1038/d41586-018-05061-9}, pmid = {29740133}, issn = {1476-4687}, mesh = {Animals ; Conservation of Natural Resources/*legislation & jurisprudence ; Endangered Species/legislation & jurisprudence ; Female ; Male ; *Parks, Recreational ; Population Dynamics ; *Ursidae ; Wilderness ; Wyoming ; }, } @article {pmid29740132, year = {2018}, author = {Else, H}, title = {Report harassment or risk losing funding, says top UK science funder.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {149}, doi = {10.1038/d41586-018-05071-7}, pmid = {29740132}, issn = {1476-4687}, mesh = {Academies and Institutes/*economics/ethics ; Bullying/prevention & control ; Female ; Financing, Organized/economics/*organization & administration ; Humans ; Male ; Research Personnel/*economics/ethics ; Research Support as Topic/economics/*organization & administration ; Sexual Harassment/*legislation & jurisprudence/prevention & control ; United Kingdom ; }, } @article {pmid29739892, year = {2018}, author = {Garcin, Y and Deschamps, P and Ménot, G and de Saulieu, G and Schefuß, E and Sebag, D and Dupont, LM and Oslisly, R and Brademann, B and Mbusnum, KG and Onana, JM and Ako, AA and Epp, LS and Tjallingii, R and Strecker, MR and Brauer, A and Sachse, D}, title = {Reply to Clist et al.: Human activity is the most probable trigger of the late Holocene rainforest crisis in Western Central Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4735-E4736}, pmid = {29739892}, issn = {1091-6490}, mesh = {Africa, Central ; Africa, Western ; *Fossils ; Human Activities ; Humans ; *Rainforest ; }, } @article {pmid29739891, year = {2018}, author = {Donahue, CJ and Glasser, MF and Preuss, TM and Rilling, JK and Van Essen, DC}, title = {Quantitative assessment of prefrontal cortex in humans relative to nonhuman primates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5183-E5192}, pmid = {29739891}, issn = {1091-6490}, support = {R24 NS092988/NS/NINDS NIH HHS/United States ; T32 EB014855/EB/NIBIB NIH HHS/United States ; F30 MH097312/MH/NIMH NIH HHS/United States ; P01 AG026423/AG/NIA NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; R01 MH060974/MH/NIMH NIH HHS/United States ; U54 MH091657/MH/NIMH NIH HHS/United States ; }, mesh = {Anatomy, Comparative ; Animals ; Female ; Humans ; Macaca/*anatomy & histology ; Magnetic Resonance Imaging ; Male ; Neuroanatomy ; Pan troglodytes/*anatomy & histology ; Prefrontal Cortex/*anatomy & histology/diagnostic imaging ; }, abstract = {Humans have the largest cerebral cortex among primates. The question of whether association cortex, particularly prefrontal cortex (PFC), is disproportionately larger in humans compared with nonhuman primates is controversial: Some studies report that human PFC is relatively larger, whereas others report a more uniform PFC scaling. We address this controversy using MRI-derived cortical surfaces of many individual humans, chimpanzees, and macaques. We present two parcellation-based PFC delineations based on cytoarchitecture and function and show that a previously used morphological surrogate (cortex anterior to the genu of the corpus callosum) substantially underestimates PFC extent, especially in humans. We find that the proportion of cortical gray matter occupied by PFC in humans is up to 1.9-fold greater than in macaques and 1.2-fold greater than in chimpanzees. The disparity is even more prominent for the proportion of subcortical white matter underlying the PFC, which is 2.4-fold greater in humans than in macaques and 1.7-fold greater than in chimpanzees.}, } @article {pmid29739890, year = {2018}, author = {Betzel, RF and Bassett, DS}, title = {Specificity and robustness of long-distance connections in weighted, interareal connectomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4880-E4889}, pmid = {29739890}, issn = {1091-6490}, support = {R01 NS099348/NS/NINDS NIH HHS/United States ; R01 MH107235/MH/NIMH NIH HHS/United States ; R01 DC009209/DC/NIDCD NIH HHS/United States ; R21 MH106799/MH/NIMH NIH HHS/United States ; R01 HD086888/HD/NICHD NIH HHS/United States ; R01 MH109520/MH/NIMH NIH HHS/United States ; R01 MH107703/MH/NIMH NIH HHS/United States ; }, mesh = {*Algorithms ; Animals ; Brain/*physiology ; *Connectome ; Datasets as Topic ; Drosophila melanogaster ; Humans ; Macaca ; Mice ; *Models, Neurological ; Nerve Net/*physiology ; Neural Pathways/*physiology ; }, abstract = {Brain areas' functional repertoires are shaped by their incoming and outgoing structural connections. In empirically measured networks, most connections are short, reflecting spatial and energetic constraints. Nonetheless, a small number of connections span long distances, consistent with the notion that the functionality of these connections must outweigh their cost. While the precise function of long-distance connections is unknown, the leading hypothesis is that they act to reduce the topological distance between brain areas and increase the efficiency of interareal communication. However, this hypothesis implies a nonspecificity of long-distance connections that we contend is unlikely. Instead, we propose that long-distance connections serve to diversify brain areas' inputs and outputs, thereby promoting complex dynamics. Through analysis of five weighted interareal network datasets, we show that long-distance connections play only minor roles in reducing average interareal topological distance. In contrast, areas' long-distance and short-range neighbors exhibit marked differences in their connectivity profiles, suggesting that long-distance connections enhance dissimilarity between areal inputs and outputs. Next, we show that-in isolation-areas' long-distance connectivity profiles exhibit nonrandom levels of similarity, suggesting that the communication pathways formed by long connections exhibit redundancies that may serve to promote robustness. Finally, we use a linearization of Wilson-Cowan dynamics to simulate the covariance structure of neural activity and show that in the absence of long-distance connections a common measure of functional diversity decreases. Collectively, our findings suggest that long-distance connections are necessary for supporting diverse and complex brain dynamics.}, } @article {pmid29739889, year = {2018}, author = {Xu, S and Huang, S and Luan, Z and Chen, T and Wei, Y and Xing, M and Li, Y and Du, C and Wang, B and Zheng, F and Wang, N and Guan, Y and Gustafsson, JÅ and Zhang, X}, title = {Farnesoid X receptor is essential for the survival of renal medullary collecting duct cells under hypertonic stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5600-5605}, doi = {10.1073/pnas.1803945115}, pmid = {29739889}, issn = {1091-6490}, mesh = {Animals ; Gene Expression Regulation ; Kidney Concentrating Ability/*physiology ; Kidney Medulla/*cytology/metabolism ; Kidney Tubules, Collecting/*cytology/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Osmotic Pressure/*physiology ; Receptors, Cytoplasmic and Nuclear/*physiology ; *Stress, Physiological ; Transcription Factors/genetics/*metabolism ; }, abstract = {Hypertonicity in renal medulla is critical for the kidney to produce concentrated urine. Renal medullary cells have to survive high medullary osmolarity during antidiuresis. Previous study reported that farnesoid X receptor (FXR), a nuclear receptor transcription factor activated by endogenous bile acids, increases urine concentrating ability by up-regulating aquaporin 2 expression in medullary collecting duct cells (MCDs). However, whether FXR is also involved in the maintenance of cell survival of MCDs under dehydration condition and hypertonic stress remains largely unknown. In the present study, we demonstrate that 24-hours water restriction selectively up-regulated renal medullary expression of FXR with little MCD apoptosis in wild-type mice. In contrast, water deprivation caused a massive apoptosis of MCDs in both global FXR gene-deficient mice and collecting duct-specific FXR knockout mice. In vitro studies showed that hypertonicity significantly increased FXR and tonicity response enhancer binding protein (TonEBP) expression in mIMCD3 cell line and primary cultured MCDs. Activation and overexpression of FXR markedly increased cell viability and decreased cell apoptosis under hyperosmotic conditions. In addition, FXR can increase gene expression and nuclear translocation of TonEBP. We conclude that FXR protects MCDs from hypertonicity-induced cell injury very likely via increasing TonEBP expression and nuclear translocation. This study provides insights into the molecular mechanism by which FXR enhances urine concentration via maintaining cell viability of MCDs under hyperosmotic condition.}, } @article {pmid29739888, year = {2018}, author = {Bowling, DL and Purves, D and Gill, KZ}, title = {Reply to Goffinet: In consonance, old ideas die hard.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4958-E4959}, pmid = {29739888}, issn = {1091-6490}, } @article {pmid29739887, year = {2018}, author = {Clist, B and Bostoen, K and de Maret, P and Eggert, MKH and Höhn, A and Mbida Mindzié, C and Neumann, K and Seidensticker, D}, title = {Did human activity really trigger the late Holocene rainforest crisis in Central Africa?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4733-E4734}, pmid = {29739887}, issn = {1091-6490}, mesh = {Africa, Central ; Fossils ; *Human Activities ; Humans ; *Rainforest ; }, } @article {pmid29739886, year = {2018}, author = {Pang, G and Smidman, M and Zhang, J and Jiao, L and Weng, Z and Nica, EM and Chen, Y and Jiang, W and Zhang, Y and Xie, W and Jeevan, HS and Lee, H and Gegenwart, P and Steglich, F and Si, Q and Yuan, H}, title = {Fully gapped d-wave superconductivity in CeCu2Si2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5343-5347}, pmid = {29739886}, issn = {1091-6490}, abstract = {The nature of the pairing symmetry of the first heavy fermion superconductor CeCu2Si2 has recently become the subject of controversy. While CeCu2Si2 was generally believed to be a d-wave superconductor, recent low-temperature specific heat measurements showed evidence for fully gapped superconductivity, contrary to the nodal behavior inferred from earlier results. Here, we report London penetration depth measurements, which also reveal fully gapped behavior at very low temperatures. To explain these seemingly conflicting results, we propose a fully gapped [Formula: see text] band-mixing pairing state for CeCu2Si2, which yields very good fits to both the superfluid density and specific heat, as well as accounting for a sign change of the superconducting order parameter, as previously concluded from inelastic neutron scattering results.}, } @article {pmid29739885, year = {2018}, author = {Goffinet, J}, title = {Little evidence for the vocal similarity hypothesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4957}, pmid = {29739885}, issn = {1091-6490}, mesh = {Animals ; *Learning ; *Vocalization, Animal ; Voice ; }, } @article {pmid29739883, year = {2018}, author = {Kwok, R}, title = {News Feature: Accidental urban oases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4800-4804}, pmid = {29739883}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; *Cities ; Humans ; *Urban Renewal ; }, } @article {pmid29739473, year = {2018}, author = {Sayedalamin, Z and Halawa, TF and Baig, M and Almutairi, O and Allam, H and Jameel, T and Gazzaz, ZJ and Atta, H}, title = {Undergraduate medical research in the Gulf Cooperation Council (GCC) countries: a descriptive study of the students' perspective.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {283}, pmid = {29739473}, issn = {1756-0500}, mesh = {*Biomedical Research ; *Education, Medical, Undergraduate ; Female ; Humans ; Male ; Middle East ; Students, Medical ; }, abstract = {OBJECTIVE: There is a lack of research-oriented physicians in several Arab countries and especially in Gulf region countries. In this context, it is important to explore medical students' perceptions and motivations towards research. The aim of the present study was to investigate research attitude, practices, and motivations among medical students from GCC countries.

RESULTS: There were 228 students who participated in this study (male 88, females 140). Thirty-eight percent of the students were participating from Saudi Arabia, 20.6% from the UAE, 17.1% from Oman, 12.7% from Kuwait and 11.4% from Bahrain. Among participants, 43.0% had experience of funded research, and 53.1% had a contribution to research. The confidence of participants in their ability to interpret and to write a research paper was quite high (70.2%). The majority of the students (87.3%) believed that undergraduate students could conduct research and can present at conferences. Improving research skills, attaining research publication, and improvement in patient care were claimed as the top three motives for conducting research. The majority (75.0%) were compelled to research to facilitate their acceptance to a residency program and 63.6% due to compulsion for a research methodology course.}, } @article {pmid29739448, year = {2018}, author = {Montenegro, FS and Correia, M and Muccillo, F and Souza E Silva, CG and De Lorenzo, A}, title = {Associations between endothelial progenitor cells, clinical characteristics and coronary restenosis in patients undergoing percutaneous coronary artery intervention.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {278}, pmid = {29739448}, issn = {1756-0500}, mesh = {Aged ; Cell Count ; Coronary Restenosis/*pathology/*surgery ; Endothelial Progenitor Cells/*metabolism/*pathology ; Female ; Humans ; Male ; *Percutaneous Coronary Intervention ; Treatment Outcome ; }, abstract = {OBJECTIVE: Endothelial progenitor cells (EPCs) are produced in the bone marrow and mobilized to the peripheral blood playing a key role in endothelial repair. The objective of this study was to evaluate circulating EPC before and after percutaneous coronary intervention (PCI) with stent implantation and their associations with coronary restenosis and adverse cardiovascular events. Venous blood was obtained before and the day after PCI. Quantification of total white blood count and identification of EPCs (CD45-CD34+CD31+CD133/2+CD309+) through immunophenotyping by flow cytometry was performed. The primary outcome was either restenosis detected by new coronary angiography or angina with myocardial ischemia at the territory of the stented coronary artery. Secondary outcomes were angina without demonstrable myocardial ischemia, acute coronary syndrome or all-cause death.

RESULTS: 37 patients were followed for 1 year. The median EPC count before PCI was 320 cells/mcl and after PCI 286 cells/mcl. A decrease of EPC count was found in 65% of the patients, while 35% displayed an increase. Primary outcomes occurred in 10.8% and the secondary in 37.8% of the patients. Despite a higher level of EPC before (402 cell/mcl) and after PCI (383 cell/mcl) in patients with the secondary outcomes, there was no significant association between EPC and cardiovascular events.}, } @article {pmid29739447, year = {2018}, author = {Hillesund, ER and Seland, S and Bere, E and Sagedal, LR and Torstveit, MK and Lohne-Seiler, H and Vistad, I and Øverby, NC}, title = {Preeclampsia and gestational weight gain in the Norwegian Fit for Delivery trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {282}, pmid = {29739447}, issn = {1756-0500}, mesh = {Adult ; *Delivery, Obstetric ; Female ; Humans ; Norway ; Pre-Eclampsia/*pathology ; Pregnancy ; *Weight Gain ; }, abstract = {OBJECTIVE: Excessive gestational weight gain is linked to risk of preeclampsia, but it is not clear whether the association is causal. The purpose of this paper was to examine gestational weight gain in the Norwegian Fit for Delivery study among women who developed preeclampsia compared to those who did not, and to further explore associations between weight gain and preeclampsia by including data on body composition (bioimpedance) assessed in the last trimester of pregnancy.

RESULTS: A total of 550 women were eligible for the study. Women who developed preeclampsia gained more weight than women who did not (difference 3.7 kg, p = 0.004), with a 3.5 kg difference in total body water observed in week 36 (p = 0.040). Adjusted for age, education, pre-pregnancy body mass index (BMI), randomization, and fat mass, a one kg increase in GWG was associated with 1.3 times higher odds of preeclampsia (OR: 1.31, 95% CI 1.15-1.49, p < 0.001). An independent inverse association between fat mass in week 36 and odds of preeclampsia was observed (OR: 0.79, 95% CI 0.68-0.92, p = 0.002). Given the observed difference in total body water, these findings point to excess fluid as the component driving the association between gestational weight gain and preeclampsia in the present study. Trial registration The NFFD trial has the Clinical Trials registration: clinicaltrial.gov NCT0100168.}, } @article {pmid29739445, year = {2018}, author = {Sorek, M and Schnytzer, Y and Ben-Asher, HW and Caspi, VC and Chen, CS and Miller, DJ and Levy, O}, title = {Setting the pace: host rhythmic behaviour and gene expression patterns in the facultatively symbiotic cnidarian Aiptasia are determined largely by Symbiodinium.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {83}, pmid = {29739445}, issn = {2049-2618}, support = {1294//Taiwan-Israel cooperative program/International ; }, mesh = {Animals ; Biological Clocks/*physiology ; Circadian Rhythm/genetics/*physiology ; Dinoflagellida/*metabolism ; Gene Expression Regulation/*genetics ; Oxygen/metabolism ; Sea Anemones/*genetics/parasitology ; Symbiosis/physiology ; }, abstract = {BACKGROUND: All organisms employ biological clocks to anticipate physical changes in the environment; however, the integration of biological clocks in symbiotic systems has received limited attention. In corals, the interpretation of rhythmic behaviours is complicated by the daily oscillations in tissue oxygen tension resulting from the photosynthetic and respiratory activities of the associated algal endosymbiont Symbiodinium. In order to better understand the integration of biological clocks in cnidarian hosts of Symbiodinium, daily rhythms of behaviour and gene expression were studied in symbiotic and aposymbiotic morphs of the sea-anemone Aiptasia diaphana.

RESULTS: The results showed that whereas circatidal (approx. 12-h) cycles of activity and gene expression predominated in aposymbiotic morphs, circadian (approx. 24-h) patterns were the more common in symbiotic morphs, where the expression of a significant number of genes shifted from a 12- to 24-h rhythm. The behavioural experiments on symbiotic A. diaphana displayed diel (24-h) rhythmicity in body and tentacle contraction under the light/dark cycles, whereas aposymbiotic morphs showed approximately 12-h (circatidal) rhythmicity. Reinfection experiments represent an important step in understanding the hierarchy of endogenous clocks in symbiotic associations, where the aposymbiotic Aiptasia morphs returned to a 24-h behavioural rhythm after repopulation with algae.

CONCLUSION: Whilst some modification of host metabolism is to be expected, the extent to which the presence of the algae modified host endogenous behavioural and transcriptional rhythms implies that it is the symbionts that influence the pace. Our results clearly demonstrate the importance of the endosymbiotic algae in determining the timing and the duration of the extension and contraction of the body and tentacles and temporal gene expression.}, } @article {pmid29739441, year = {2018}, author = {Toru, M and Beyene, G and Kassa, T and Gizachew, Z and Howe, R and Yeshitila, B}, title = {Prevalence and phenotypic characterization of Enterococcus species isolated from clinical samples of pediatric patients in Jimma University Specialized Hospital, south west Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {281}, pmid = {29739441}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/pharmacology/therapeutic use ; Child ; Child, Preschool ; Demography ; Enterococcus/*isolation & purification/pathogenicity ; Ethiopia/epidemiology ; Female ; Gram-Positive Bacterial Infections/drug therapy/epidemiology/microbiology ; *Hospitals, University ; Humans ; Infant ; Infant, Newborn ; Male ; Microbial Sensitivity Tests ; Phenotype ; Prevalence ; Risk Factors ; Vancomycin Resistance/drug effects ; Virulence Factors/metabolism ; }, abstract = {OBJECTIVE: This study was done to determine the prevalence and phenotypic characterization of Enterococcus species isolated from clinical samples of pediatric patients in Jimma University Specialized Hospital, Southwest Ethiopia.

RESULTS: The overall prevalence of Enterococci species was 5.5% (22/403). Five (22.7%) of Enterococci species were vancomycin resistant. Haemolysin, gelatinase and biofilm production was seen among 45.5, 68.2 and 77.3% of isolates respectively. The overall rate of antibiotic resistance was 95.5% (21/22). High resistance was observed against norfloxacin (87.5%), and tetracycline (77.3%). Whereas, low resistance (36.5%) was observed against ciprofloxacin and eighteen (80.8%) of the isolates were multi-drug resistant.}, } @article {pmid29739437, year = {2018}, author = {Torres, R and Dorriz, D and Saviola, B}, title = {Induction of the acid inducible lipF promoter is reversibly inhibited in pH ranges of pH 4.2-4.0.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {284}, pmid = {29739437}, issn = {1756-0500}, mesh = {Acids/*pharmacology ; Bacterial Proteins/*genetics/metabolism ; Escherichia coli/drug effects ; Gene Expression Regulation, Bacterial/*drug effects ; Hydrogen-Ion Concentration ; Mycobacterium smegmatis/drug effects/*genetics ; *Promoter Regions, Genetic ; }, abstract = {OBJECTIVE: In the human body pathogenic mycobacteria encounter low pH within the phagosomes of macrophages where they reside after being internalized by the host cell. Low pH within macrophages has been shown to induce expression of a variety of genes within these bacteria. It had been previously observed that the Mycobacterium tuberculosis lipF promoter is transcriptionally upregulated between pHs 4.5-6.4 in Mycobacterium smegmatis, with an upper pH limit of 6.4 capable of promoter induction. To better understand the parameters of acid induced gene expression, we sought to determine the lower pH limit capable of lipF promoter induction.

RESULTS: As we had already determined an upper pH limit, we determine here that there is a lower limit of pH's capable of upregulating the lipF promoter, with pH below 4.3 not positively upregulating the promoter. At non-inducing pH 4.2 the bacterial cells remain viable in the absence of acid induced lipF promoter upregulation and subsequent exposure to acid pH 5.0 results in lipF promoter upregulation. There appears to be a lower limit of pH capable of upregulating lipF promoter expression and this limit is not due to cell death.}, } @article {pmid29739428, year = {2018}, author = {Oweis, AO and Alshelleh, SA}, title = {Incidence and outcomes of acute kidney injury in octogenarians in Jordan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {279}, pmid = {29739428}, issn = {1756-0500}, mesh = {Acute Kidney Injury/*epidemiology ; Aged, 80 and over ; Female ; Humans ; Incidence ; Jordan/epidemiology ; Male ; Proportional Hazards Models ; Treatment Outcome ; }, abstract = {OBJECTIVE: Improvements in the health care system, resulted in a greater number of geriatric patients diagnosed with acute kidney injury (AKI). We evaluated the incidence and outcome of AKI in octogenarians, as studies in the Middle-East region are few; moreover, treatment approaches, in addition to medical decisions, may require special consideration for advanced age to improve the outcomes.

RESULTS: At King Abdullah II teaching and referral hospital, we recruited patients aged 80-90 years who were admitted to the medical floor between January 2010 and December 2013. Patients were followed-up for at least 1 year after discharge.850 patients were admitted during the study period. Of these, 135 were excluded from our analysis. The most common admission diagnoses were uncontrolled diabetes mellitus and acute coronary syndrome. AKI occurred in 216 patients (30.2%). Using the acute kidney injury network classification; stage 1, stage 2, and stage 3 disease were present in 59, 17.5, and 23.5% of patients, respectively. Of the 115 patients who died before discharge (16.1%), 87 (75.6%) had developed AKI. Hypertension, the use of angiotensin receptor blockers and non-steroidal anti-inflammatory drugs, heart failure, and exposure to radiologic contrast media were significant risk factors for AKI.}, } @article {pmid29739419, year = {2018}, author = {Alharthi, A and Beck, D and Howard, DR and Hillmen, P and Oates, M and Pettitt, A and Wagner, SD}, title = {An increased fraction of circulating miR-363 and miR-16 is particle bound in patients with chronic lymphocytic leukaemia as compared to normal subjects.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {280}, pmid = {29739419}, issn = {1756-0500}, support = {07/01/38//Health Technology Assessment Programme/ ; }, mesh = {Aged ; Blood Proteins/metabolism ; Female ; Humans ; Leukemia, Lymphocytic, Chronic, B-Cell/*blood/*genetics ; Male ; MicroRNAs/*blood/metabolism ; Middle Aged ; Reference Standards ; Treatment Outcome ; }, abstract = {OBJECTIVES: In vitro culture studies have shown that miR-363 is enriched in extracellular vesicles from chronic lymphocytic leukaemia cells. We wondered whether miR-363 was detectable in plasma, which is an essential precondition for further studies to assess its usefulness as a biomarker. Using samples from two clinical trials: one enrolling patients with advanced disease and the other asymptomatic patients with early stage disease, we determined plasma miR-363 levels and secondly investigated the distribution of this miRNA between plasma and particle bound fractions in patients and normal subjects.

RESULTS: Advanced disease (n = 95) was associated with higher levels of miR-363 than early stage disease (n = 45) or normal subjects (n = 11) but there was no association with markers of prognosis. The distribution of specific miRNA between particle bound and plasma protein fractions was investigated using size exclusion chromatography on plasma from patients (n = 4) and normal subjects (n = 3). ~ 20% of total miR-16 and miR-363 is particle bound in patients while there was no detectable particle bound material in normal subjects. Our work demonstrates that miR-363 levels are raised in chronic lymphocytic leukaemia patients and raises the possibility that distribution of circulating miRNA between plasma fractions differs in health and disease.}, } @article {pmid29739336, year = {2018}, author = {Sekar, S and Cuyugan, L and Adkins, J and Geiger, P and Liang, WS}, title = {Circular RNA expression and regulatory network prediction in posterior cingulate astrocytes in elderly subjects.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {340}, pmid = {29739336}, issn = {1471-2164}, support = {P30 AG019610/AG/NIA NIH HHS/United States ; U24 NS072026/NS/NINDS NIH HHS/United States ; P30AG019610//National Institute on Aging/ ; ADHS14-052688//Arizona Department of Health Services/ ; }, mesh = {Aged ; Alzheimer Disease/*genetics/pathology ; Astrocytes/cytology/*metabolism ; Case-Control Studies ; Cells, Cultured ; Female ; *Gene Regulatory Networks ; *Genetic Markers ; Gyrus Cinguli/cytology/*metabolism ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; MicroRNAs/genetics ; RNA/*genetics ; RNA, Messenger/genetics ; }, abstract = {BACKGROUND: Circular RNAs (circRNAs) are a novel class of endogenous, non-coding RNAs that form covalently closed continuous loops and that are both highly conserved and abundant in the mammalian brain. A role for circRNAs in sponging microRNAs (miRNAs) has been proposed, but the circRNA-miRNA-mRNA interaction networks in human brain cells have not been defined. Therefore, we identified circRNAs in RNA sequencing data previously generated from astrocytes microdissected from the posterior cingulate (PC) of Alzheimer's disease (AD) patients (N = 10) and healthy elderly controls (N = 10) using four circRNA prediction algorithms - CIRI, CIRCexplorer, find_circ and KNIFE.

RESULTS: Overall, utilizing these four tools, we identified a union of 4438 unique circRNAs across all samples, of which 70.3% were derived from exonic regions. Notably, the widely reported CDR1as circRNA was detected in all samples across both groups by find_circ. Given the putative miRNA regulatory function of circRNAs, we identified potential miRNA targets of circRNAs, and further, delineated circRNA-miRNA-mRNA networks using in silico methods. Pathway analysis of the genes regulated by these miRNAs identified significantly enriched immune response pathways, which is consistent with the known function of astrocytes as immune sensors in the brain.

CONCLUSIONS: In this study, we performed circRNA detection on cell-specific transcriptomic data and identified potential circRNA-miRNA-mRNA regulatory networks in PC astrocytes. Given the known function of astrocytes in cerebral innate immunity and our identification of significantly enriched immune response pathways, the circRNAs we identified may be associated with such key functions. While we did not detect recurrent differentially expressed circRNAs in the context of healthy controls or AD, we report for the first time circRNAs and their potential regulatory impact in a cell-specific and region-specific manner in aged subjects. These predicted regulatory network and pathway analyses may help provide new insights into transcriptional regulation in the brain.}, } @article {pmid29739335, year = {2018}, author = {Zheng, Z and Aweya, JJ and Wang, F and Yao, D and Lun, J and Li, S and Ma, H and Zhang, Y}, title = {Acute Hepatopancreatic Necrosis Disease (AHPND) related microRNAs in Litopenaeus vannamei infected with AHPND-causing strain of Vibrio parahemolyticus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {335}, pmid = {29739335}, issn = {1471-2164}, support = {31372558//National Natural Science Foundation of China/ ; 31672689//National Natural Science Foundation of China (CN)/ ; 2017A030311032//Natural Science Foundation of Guangdong Province/ ; }, mesh = {Acute Disease ; Animals ; *Gene Expression Profiling ; Hepatopancreas/*pathology ; MicroRNAs/*genetics ; Necrosis/microbiology ; Penaeidae/*microbiology ; Vibrio parahaemolyticus/*genetics/*physiology ; }, abstract = {BACKGROUND: Acute hepatopancreatic necrosis disease (AHPND) has emerged as a major debilitating disease that causes massive shrimp death resulting in substantial economic losses in shrimp aquaculture. Given that several diseases and infections have been associated with microRNAs (miRNAs), we conducted a comparative transcriptomic analysis using the AHPND (VA) and non-AHPND (VN) strains of Vibrio parahemolyticus to identify miRNAs potentially involved in AHPND pathogenesis in Litopenaeus vannamei.

RESULTS: A total of 83 miRNAs (47 upregulated and 36 downregulated) were significantly differentially expressed between the VA and VN challenged groups, while 222 target genes of these miRNAs were predicted. Functional enrichment analysis revealed that the miRNAs target genes were involved in multiple biological processes including metabolic pathways, amoebiasis, Vibrio cholerae infection etc. Finally, interaction network and qPCR (Real-time Quantitative PCR) analysis of 12 potential key AHPND-related miRNAs and their predicted target genes, revealed their possible involvement in modulating several immune-related processes in the pathogenesis of AHPND.

CONCLUSIONS: We have shown using comparative transcriptomic analysis, miRNAs and their target genes that are responsive to AHPND V. parahemolyticus infection in shrimp, therefore suggesting their possible role in defense response to AHPND V. parahemolyticus infection.}, } @article {pmid29739334, year = {2018}, author = {Uyhelji, HA and Kupfer, DM and White, VL and Jackson, ML and Van Dongen, HPA and Burian, DM}, title = {Exploring gene expression biomarker candidates for neurobehavioral impairment from total sleep deprivation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {341}, pmid = {29739334}, issn = {1471-2164}, support = {R01 HL105768/HL/NHLBI NIH HHS/United States ; DTFAAC-11-A-00003//Federal Aviation Administration/ ; R01HL105768//National Heart, Lung, and Blood Institute/ ; }, mesh = {Adult ; Biomarkers/*metabolism ; Female ; *Gene Regulatory Networks ; Healthy Volunteers ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; MicroRNAs/genetics ; Neuropsychological Tests ; Psychomotor Performance ; RNA, Messenger/genetics/*metabolism ; Sleep/*physiology ; Sleep Deprivation/*complications/genetics/pathology ; Sleep Initiation and Maintenance Disorders/*diagnosis/etiology/pathology ; Time Factors ; Wakefulness ; Young Adult ; }, abstract = {BACKGROUND: Although sleep deprivation is associated with neurobehavioral impairment that may underlie significant risks to performance and safety, there is no reliable biomarker test to detect dangerous levels of impairment from sleep loss in humans. This study employs microarrays and bioinformatics analyses to explore candidate gene expression biomarkers associated with total sleep deprivation (TSD), and more specifically, the phenotype of neurobehavioral impairment from TSD. Healthy adult volunteers were recruited to a sleep laboratory for seven consecutive days (six nights). After two Baseline nights of 10 h time in bed, 11 subjects underwent an Experimental phase of 62 h of continuous wakefulness, followed by two Recovery nights of 10 h time in bed. Another six subjects underwent a well-rested Control condition of 10 h time in bed for all six nights. Blood was drawn for measuring gene expression on days two, four, and six at 4 h intervals from 08:00 to 20:00 h, corresponding to 12 timepoints across one Baseline, one Experimental, and one Recovery day.

RESULTS: Altogether 212 genes changed expression in response to the TSD Treatment, with most genes exhibiting down-regulation during TSD. Also, 28 genes were associated with neurobehavioral impairment as measured by the Psychomotor Vigilance Test. The results support previous findings associating TSD with the immune response and ion signaling, and reveal novel candidate biomarkers such as the Speedy/RINGO family of cell cycle regulators.

CONCLUSIONS: This study serves as an important step toward understanding gene expression changes during sleep deprivation. In addition to exploring potential biomarkers for TSD, this report presents novel candidate biomarkers associated with lapses of attention during TSD. Although further work is required for biomarker validation, analysis of these genes may aid fundamental understanding of the impact of TSD on neurobehavioral performance.}, } @article {pmid29739332, year = {2018}, author = {Costello, M and Fleharty, M and Abreu, J and Farjoun, Y and Ferriera, S and Holmes, L and Granger, B and Green, L and Howd, T and Mason, T and Vicente, G and Dasilva, M and Brodeur, W and DeSmet, T and Dodge, S and Lennon, NJ and Gabriel, S}, title = {Characterization and remediation of sample index swaps by non-redundant dual indexing on massively parallel sequencing platforms.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {332}, pmid = {29739332}, issn = {1471-2164}, support = {UM1 HG008895/HG/NHGRI NIH HHS/United States ; UM1HG008895//Center for Common Disease/ ; }, mesh = {DNA/chemistry/isolation & purification/metabolism ; Gene Library ; Genome, Human ; *High-Throughput Nucleotide Sequencing ; Humans ; Sequence Analysis/*methods ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Here we present an in-depth characterization of the mechanism of sequencer-induced sample contamination due to the phenomenon of index swapping that impacts Illumina sequencers employing patterned flow cells with Exclusion Amplification (ExAmp) chemistry (HiSeqX, HiSeq4000, and NovaSeq). We also present a remediation method that minimizes the impact of such swaps.

RESULTS: Leveraging data collected over a two-year period, we demonstrate the widespread prevalence of index swapping in patterned flow cell data. We calculate mean swap rates across multiple sample preparation methods and sequencer models, demonstrating that different library methods can have vastly different swapping rates and that even non-ExAmp chemistry instruments display trace levels of index swapping. We provide methods for eliminating sample data cross contamination by utilizing non-redundant dual indexing for complete filtering of index swapped reads, and share the sequences for 96 non-combinatorial dual indexes we have validated across various library preparation methods and sequencer models. Finally, using computational methods we provide a greater insight into the mechanism of index swapping.

CONCLUSIONS: Index swapping in pooled libraries is a prevalent phenomenon that we observe at a rate of 0.2 to 6% in all sequencing runs on HiSeqX, HiSeq 4000/3000, and NovaSeq. Utilizing non-redundant dual indexing allows for the removal (flagging/filtering) of these swapped reads and eliminates swapping induced sample contamination, which is critical for sensitive applications such as RNA-seq, single cell, blood biopsy using circulating tumor DNA, or clinical sequencing.}, } @article {pmid29739331, year = {2018}, author = {Song, H and Yi, H and Lee, M and Han, CT and Lee, J and Kim, H and Park, JI and Nou, IS and Kim, SJ and Hur, Y}, title = {Purple Brassica oleracea var. capitata F. rubra is due to the loss of BoMYBL2-1 expression.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {82}, pmid = {29739331}, issn = {1471-2229}, support = {213007-05-1-SB620//Golden Seed Project/ ; }, mesh = {Anthocyanins/genetics/metabolism ; Brassica/*genetics/metabolism ; Color ; Genes, Plant/genetics/physiology ; Genetic Markers/genetics ; Plant Proteins/genetics/metabolism/*physiology ; Polymerase Chain Reaction ; Promoter Regions, Genetic/genetics/physiology ; Repressor Proteins/genetics/metabolism/*physiology ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Water-soluble anthocyanin pigments are important ingredients in health-improving supplements and valuable for the food industry. Although great attention has been paid to the breeding and production of crops containing high levels of anthocyanin, genetic variation in red or purple cabbages (Brassica oleracea var. capitata F. rubra) has not yet been characterized at the molecular level. In this study, we identified the mechanism responsible for the establishment of purple color in cabbages.

RESULTS: BoMYBL2-1 is one of the regulatory genes in the anthocyanin biosynthesis pathway in cabbages. It is a repressor whose expression is inversely correlated to anthocyanin synthesis and is not detectable in purple cabbages. Sequence analysis of purple cabbages revealed that most lacked BoMYBL2-1 coding sequences, although a few had a substitution in the region of the promoter 347 bp upstream of the gene that was associated with an absence of BoMYBL2-1 expression. Lack of transcriptional activity of the substitution-containing promoter was confirmed using transgenic Arabidopsis plants transformed with promoter::GUS fusion constructs. The finding that the defect in BoMYBL2-1 expression was solely responsible for purple coloration in cabbages was further demonstrated using genomic PCR and RT-PCR analyses of many other structural and regulatory genes in anthocyanin biosynthesis. Molecular markers for purple cabbages were developed and validated using 69 cabbage lines.

CONCLUSION: Expression of BoMYBL2-1 was inversely correlated to anthocyanin content, and purple color in cabbages resulted from a loss of BoMYBL2-1 expression, caused by either the promoter substitution or deletion of the gene. This is the first report of molecular markers that distinguish purple cabbages. Such markers will be useful for the production of intraspecific and interspecific hybrids for functional foods, and for industrial purposes requiring high anthocyanin content.}, } @article {pmid29739330, year = {2018}, author = {Vijay, S and Rawal, R and Kadian, K and Singh, J and Adak, T and Sharma, A}, title = {Proteome-wide analysis of Anopheles culicifacies mosquito midgut: new insights into the mechanism of refractoriness.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {337}, pmid = {29739330}, issn = {1471-2164}, support = {BT/PR8221/MED/12/617/2013//Department of Biotechnology , Ministry of Science and Technology/ ; No.3/1/3/PDF(7)/2013-HRD.//Indian Council of Medical Research (IN)/ ; }, mesh = {Amino Acid Sequence ; Animals ; Anopheles/embryology/*metabolism ; Intestines/*embryology ; Protein Interaction Maps ; *Proteomics ; }, abstract = {BACKGROUND: Midgut invasion, a major bottleneck for malaria parasites transmission is considered as a potential target for vector-parasite interaction studies. New intervention strategies are required to explore the midgut proteins and their potential role in refractoriness for malaria control in Anopheles mosquitoes. To better understand the midgut functional proteins of An. culicifacies susceptible and refractory species, proteomic approaches coupled with bioinformatics analysis is an effective means in order to understand the mechanism of refractoriness. In the present study, an integrated in solution- in gel trypsin digestion approach, along with Isobaric tag for relative and absolute quantitation (iTRAQ)-Liquid chromatography/Mass spectrometry (LC/MS/MS) and data mining were performed to identify the proteomic profile and differentially expressed proteins in Anopheles culicifacies susceptible species A and refractory species B.

RESULTS: Shot gun proteomics approaches led to the identification of 80 proteins in An. culicifacies susceptible species A and 92 in refractory species B and catalogue was prepared. iTRAQ based proteomic analysis identified 48 differentially expressed proteins from total 130 proteins. Of these, 41 were downregulated and 7 were upregulated in refractory species B in comparison to susceptible species A. We report that the altered midgut proteins identified in naturally refractory mosquitoes are involved in oxidative phosphorylation, antioxidant and proteolysis process that may suggest their role in parasite growth inhibition. Furthermore, real time polymerase chain reaction (PCR) analysis of few proteins indicated higher expression of iTRAQ upregulated protein in refractory species than susceptible species.

CONCLUSION: This study elucidates the first proteome of the midguts of An. culicifacies sibling species that attempts to analyze unique proteogenomic interactions to provide insights for better understanding of the mechanism of refractoriness. Functional implications of these upregulated proteins in refractory species may reflect the phenotypic characteristics of the mosquitoes and will improve our understandings of blood meal digestion process, parasite vector interactions and proteomes of other vectors of human diseases for development of novel vector control strategies.}, } @article {pmid29739327, year = {2018}, author = {Ren, W and Xie, J and Hou, X and Li, X and Guo, H and Hu, N and Kong, L and Zhang, J and Chang, C and Wu, Z}, title = {Potential molecular mechanisms of overgrazing-induced dwarfism in sheepgrass (Leymus chinensis) analyzed using proteomic data.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {81}, pmid = {29739327}, issn = {1471-2229}, support = {2014CB138804//National Key Basic Research and Development Program/ ; 31502008//National Natural Sciences Foundation of China/ ; 2016MS0323//Natural Sciences Foundation of Inner Mongolia/ ; }, mesh = {Amino Acids/metabolism ; Animal Husbandry ; Chromatography, High Pressure Liquid ; Gene Expression Regulation, Plant ; Mass Spectrometry ; Metabolic Networks and Pathways ; Plant Proteins/*metabolism/physiology ; Poaceae/*growth & development/metabolism/physiology ; Proteomics ; Spectrometry, Mass, Electrospray Ionization ; }, abstract = {BACKGROUND: This study was designed to reveal potential molecular mechanisms of long-term overgrazing-induced dwarfism in sheepgrass (Leymus chinensis).

METHODS: An electrospray ionisation mass spectrometry system was used to generate proteomic data of dwarf sheepgrass from a long-term overgrazed rangeland and normal sheepgrass from a long-term enclosed rangeland. Differentially expressed proteins (DEPs) between dwarf and normal sheepgrass were identified, after which their potential functions and interactions with each other were predicted. The expression of key DEPs was confirmed by high-performance liquid chromatography mass spectrometry (HPLC-MS) using a multiple reaction monitoring method.

RESULTS: Compared with normal sheepgrass, a total of 51 upregulated and 53 downregulated proteins were identified in dwarf sheepgrass. The amino acids biosynthesis pathway was differentially enriched between the two conditions presenting DEPs, such as SAT5_ARATH and DAPA_MAIZE. The protein-protein interaction (PPI) network revealed a possible interaction between RPOB2_LEPTE, A0A023H9M8_9STRA, ATPB_DIOEL, RBL_AMOTI and DNAK_GRATL. Four modules were also extracted from the PPI network. The HPLC-MS analysis confirmed the upregulation and downregulation of ATPB_DIOEL and DNAK_GRATL, respectively in dwarf samples compared with in the controls.

CONCLUSIONS: The upregulated ATPB_DIOEL and downregulated DNAK_GRATL as well as proteins that interact with them, such as RPOB2_LEPTE, A0A023H9M8_9STRA and RBL_AMOTI, may be associated with the long-term overgrazing-induced dwarfism in sheepgrass.}, } @article {pmid29739325, year = {2018}, author = {Zhu, M and Meng, X and Cai, J and Li, G and Dong, T and Li, Z}, title = {Basic leucine zipper transcription factor SlbZIP1 mediates salt and drought stress tolerance in tomato.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {83}, pmid = {29739325}, issn = {1471-2229}, support = {31700226 and 31501352//National Natural Science Foundation of China/ ; BK20160215//Youth Fund of the Natural Science Foundation of Jiangsu Province of China/ ; 16KJB210004//Natural science fund for colleges and universities in Jiangsu Province/ ; 15XLR030//Natural science fund of Jiangsu normal university/ ; }, mesh = {Abscisic Acid/metabolism ; Basic-Leucine Zipper Transcription Factors/genetics/*physiology ; Catalase/metabolism ; Chlorophyll/metabolism ; Dehydration ; Gene Expression Regulation, Plant ; Gene Silencing ; Genes, Plant/genetics/physiology ; Lycopersicon esculentum/*genetics/physiology ; Malondialdehyde/metabolism ; Plant Proteins/genetics/*physiology ; Plants, Genetically Modified ; Salt Stress ; }, abstract = {BACKGROUND: Basic region/leucine zipper (bZIP) transcription factors perform as crucial regulators in ABA-mediated stress response in plants. Nevertheless, the functions for most bZIP family members in tomato remain to be deciphered.

RESULTS: Here we examined the functional characterization of SlbZIP1 under salt and drought stresses in tomato. Silencing of SlbZIP1 in tomato resulted in reduced expression of multiple ABA biosynthesis- and signal transduction-related genes in transgenic plants. In stress assays, SlbZIP1-RNAi transgenic plants exhibited reduced tolerance to salt and drought stresses compared with WT plants, as are evaluated by multiple physiological parameters associated with stress responses, such as decreased ABA, chlorophyll contents and CAT activity, and increased MDA content. In addition, RNA-seq analysis of transgenic plants revealed that the transcription levels of multiple genes encoding defense proteins related to responses to abiotic stress (e.g. endochitinase, peroxidases, and lipid transfer proteins) and biotic stress (e.g. pathogenesis-related proteins) were downregulated in SlbZIP1-RNAi plants, suggesting that SlbZIP1 plays a role in regulating the genes related to biotic and abiotic stress response.

CONCLUSIONS: Collectively, the data suggest that SlbZIP1 exerts an essential role in salt and drought stress tolerance through modulating an ABA-mediated pathway, and SlbZIP1 may hold potential applications in the engineering of salt- and drought-tolerant tomato cultivars.}, } @article {pmid29739323, year = {2018}, author = {Angelone, S and Jowers, MJ and Molinar Min, AR and Fandos, P and Prieto, P and Pasquetti, M and Cano-Manuel, FJ and Mentaberre, G and Olvera, JRL and Ráez-Bravo, A and Espinosa, J and Pérez, JM and Soriguer, RC and Rossi, L and Granados, JE}, title = {Hidden MHC genetic diversity in the Iberian ibex (Capra pyrenaica).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {28}, pmid = {29739323}, issn = {1471-2156}, abstract = {BACKGROUND: Defining hidden genetic diversity within species is of great significance when attempting to maintain the evolutionary potential of natural populations and conduct appropriate management. Our hypothesis is that isolated (and eventually small) wild animal populations hide unexpected genetic diversity due to their maintenance of ancient polymorphisms or introgressions.

RESULTS: We tested this hypothesis using the Iberian ibex (Capra pyrenaica) as an example. Previous studies based on large sample sizes taken from its principal populations have revealed that the Iberian ibex has a remarkably small MHC DRB1 diversity (only six remnant alleles) as a result of recent population bottlenecks and a marked demographic decline that has led to the extinction of two recognized subspecies. Extending on the geographic range to include non-studied isolated Iberian ibex populations, we sequenced a new MHC DRB1 in what seemed three small isolated populations in Southern Spain (n = 132). The findings indicate a higher genetic diversity than previously reported in this important gene. The newly discovered allele, MHC DRB1*7, is identical to one reported in the domestic goat C. aegagrus hircus. Whether or not this is the result of ancient polymorphisms maintained by balancing selection or, alternatively, introgressions from domestic goats through hybridization needs to be clarified in future studies. However, hybridization between Iberian ibex and domestic goats has been reported in Spain and the fact that the newly discovered allele is only present in one of the small isolated populations and not in the others suggests introgression. The new discovered allele is not expected to increase fitness in C. pyrenaica since it generates the same protein as the existing MHC DRB1*6. Analysis of a microsatellite locus (OLADRB1) near the new MHC DRB1*7 gene reveals a linkage disequilibrium between these two loci. The allele OLADRB1, 187 bp in length, was unambiguously linked to the MHC DRB1*7 allele. This enabled us to perform a DRB-STR matching method for the recently discovered MHC allele.

CONCLUSIONS: This finding is critical for the conservation of the Iberian ibex since it directly affects the identification of the units of this species that should be managed and conserved separately (Evolutionarily Significant Units).}, } @article {pmid29739322, year = {2018}, author = {Cheng, Y and Zhang, Y and Liu, C and Ai, P and Liu, J}, title = {Identification of genes regulating ovary differentiation after pollination in hazel by comparative transcriptome analysis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {84}, pmid = {29739322}, issn = {1471-2229}, support = {31770723//National Natural Science Foundation of China/ ; 31370683//National Natural Science Foundation of China/ ; 31670681//National Natural Science Foundation of China/ ; }, mesh = {Corylus/*genetics/growth & development/physiology ; Flowers/genetics/*growth & development ; Fruit/growth & development ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Genes, Plant/*genetics/physiology ; Indoleacetic Acids/metabolism ; Plant Growth Regulators/metabolism ; Pollination ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, DNA ; Signal Transduction ; }, abstract = {BACKGROUND: Hazel (Corylus spp.) exhibits ovary differentiation and development that is initiated from the ovary primordium after pollination, conferring the plant with a unique delayed fertilization. Failure of development of the ovary and ovule after pollination can lead to ovary abortion and blank fruit formation, respectively, with consequent yield loss. However, the genes involved in ovary and ovule differentiation and development are largely unknown.

RESULTS: In unpollinated pistillate inflorescences (stage F), the stigma shows an extension growth pattern. After pollination, a rudimentary ovary begins to form (stage S), followed by ovule differentiation (stage T) and growth (stage FO). Total RNA was obtained from pistillate inflorescences or young ovaries at stage F, S, T and FO, and sequencing was carried out on a HiSeq 4000 system. De novo assembly of sequencing data yielded 62.58 Gb of nucleotides and 90,726 unigenes; 5524, 3468, and 8714 differentially expressed transcripts were identified in F-vs-S, S-vs-T, and T-vs-FO paired comparisons, respectively. An analysis of F-vs-S, S-vs-T, and T-vs-FO paired comparisons based on annotations in the Kyoto Encyclopedia of Genes and Genomes revealed six pathways that were significantly enriched during ovary differentiation, including ko04075 (Plant hormone signal transduction). Auxin level increased after pollination, and an immunohistochemical analysis indicated that auxin was enriched at the growth center of pistillate inflorescences and young ovaries. These results indicate that genes related to auxin biosynthesis, transport, signaling, the floral quartet model, and flower development may regulate ovary and ovule differentiation and development in hazel.

CONCLUSIONS: Our findings provide insight into the molecular mechanisms of ovary differentiation and development after pollination in this economically valuable plant.}, } @article {pmid29739321, year = {2018}, author = {Tiley, GP and Kimball, RT and Braun, EL and Burleigh, JG}, title = {Comparison of the Chinese bamboo partridge and red Junglefowl genome sequences highlights the importance of demography in genome evolution.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {336}, pmid = {29739321}, issn = {1471-2164}, support = {DEB-1208428//National Science Foundation/ ; DEB-1118823//National Science Foundation/ ; DEB-1118823//National Science Foundation/ ; }, mesh = {Animals ; *Evolution, Molecular ; Galliformes/*genetics ; Gene Ontology ; *Genomics ; Heterozygote ; Molecular Sequence Annotation ; }, abstract = {BACKGROUND: Recent large-scale whole genome sequencing efforts in birds have elucidated broad patterns of avian phylogeny and genome evolution. However, despite the great interest in economically important phasianids like Gallus gallus (Red Junglefowl, the progenitor of the chicken), we know little about the genomes of closely related species. Gallus gallus is highly sexually dichromatic and polygynous, but its sister genus, Bambusicola, is smaller, sexually monomorphic, and monogamous with biparental care. We sequenced the genome of Bambusicola thoracicus (Chinese Bamboo Partridge) using a single insert library to test hypotheses about genome evolution in galliforms. Selection acting at the phenotypic level could result in more evidence of positive selection in the Gallus genome than in Bambusicola. However, the historical range size of Bambusicola was likely smaller than Gallus, and demographic effects could lead to higher rates of nonsynonymous substitution in Bambusicola than in Gallus.

RESULTS: We generated a genome assembly suitable for evolutionary analyses. We examined the impact of selection on coding regions by examining shifts in the average nonsynonymous to synonymous rate ratio (dN/dS) and the proportion of sites subject to episodic positive selection. We observed elevated dN/dS in Bambusicola relative to Gallus, which is consistent with our hypothesis that demographic effects may be important drivers of genome evolution in Bambusicola. We also demonstrated that alignment error can greatly inflate estimates of the number of genes that experienced episodic positive selection and heterogeneity in dN/dS. However, overall patterns of molecular evolution were robust to alignment uncertainty. Bambusicola thoracicus has higher estimates of heterozygosity than Gallus gallus, possibly due to migration events over the past 100,000 years.

CONCLUSIONS: Our results emphasized the importance of demographic processes in generating the patterns of variation between Bambusicola and Gallus. We also demonstrated that genome assemblies generated using a single library can provide valuable insights into avian evolutionary history and found that it is important to account for alignment uncertainty in evolutionary inferences from draft genomes.}, } @article {pmid29739320, year = {2018}, author = {Auvinet, J and Graça, P and Belkadi, L and Petit, L and Bonnivard, E and Dettaï, A and Detrich, WH and Ozouf-Costaz, C and Higuet, D}, title = {Mobilization of retrotransposons as a cause of chromosomal diversification and rapid speciation: the case for the Antarctic teleost genus Trematomus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {339}, doi = {10.1186/s12864-018-4714-x}, pmid = {29739320}, issn = {1471-2164}, support = {OPP 01-32032//Institut Polaire Français Paul Emile Victor/ ; PLR-1444167//National Science Foundation/ ; }, mesh = {Animals ; Antarctic Regions ; Chromosome Mapping ; *Chromosomes ; Evolution, Molecular ; *Genome ; Perciformes/*classification/*genetics ; Phylogeny ; *Retroelements ; Species Specificity ; }, abstract = {BACKGROUND: The importance of transposable elements (TEs) in the genomic remodeling and chromosomal rearrangements that accompany lineage diversification in vertebrates remains the subject of debate. The major impediment to understanding the roles of TEs in genome evolution is the lack of comparative and integrative analyses on complete taxonomic groups. To help overcome this problem, we have focused on the Antarctic teleost genus Trematomus (Notothenioidei: Nototheniidae), as they experienced rapid speciation accompanied by dramatic chromosomal diversity. Here we apply a multi-strategy approach to determine the role of large-scale TE mobilization in chromosomal diversification within Trematomus species.

RESULTS: Despite the extensive chromosomal rearrangements observed in Trematomus species, our measurements revealed strong interspecific genome size conservation. After identifying the DIRS1, Gypsy and Copia retrotransposon superfamilies in genomes of 13 nototheniid species, we evaluated their diversity, abundance (copy numbers) and chromosomal distribution. Four families of DIRS1, nine of Gypsy, and two of Copia were highly conserved in these genomes; DIRS1 being the most represented within Trematomus genomes. Fluorescence in situ hybridization mapping showed preferential accumulation of DIRS1 in centromeric and pericentromeric regions, both in Trematomus and other nototheniid species, but not in outgroups: species of the Sub-Antarctic notothenioid families Bovichtidae and Eleginopsidae, and the non-notothenioid family Percidae.

CONCLUSIONS: In contrast to the outgroups, High-Antarctic notothenioid species, including the genus Trematomus, were subjected to strong environmental stresses involving repeated bouts of warming above the freezing point of seawater and cooling to sub-zero temperatures on the Antarctic continental shelf during the past 40 millions of years (My). As a consequence of these repetitive environmental changes, including thermal shocks; a breakdown of epigenetic regulation that normally represses TE activity may have led to sequential waves of TE activation within their genomes. The predominance of DIRS1 in Trematomus species, their transposition mechanism, and their strategic location in "hot spots" of insertion on chromosomes are likely to have facilitated nonhomologous recombination, thereby increasing genomic rearrangements. The resulting centric and tandem fusions and fissions would favor the rapid lineage diversification, characteristic of the nototheniid adaptive radiation.}, } @article {pmid29739319, year = {2018}, author = {Lajhar, SA and Brownlie, J and Barlow, R}, title = {Characterization of biofilm-forming capacity and resistance to sanitizers of a range of E. coli O26 pathotypes from clinical cases and cattle in Australia.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {41}, pmid = {29739319}, issn = {1471-2180}, abstract = {BACKGROUND: The formation of biofilms and subsequent encasement of bacterial cells in a complex matrix can enhance resistance to antimicrobials and sterilizing agents making these organisms difficult to eradicate and control. The aim of this study was to evaluate and compare the capacity of 40 E. coli O26 isolates of enterohemorrhagic E. coli (EHEC, n = 27), potential EHEC (pEHEC, n = 3), atypical enteropathogenic E. coli (aEPEC, n = 8) and non-toxigenic E. coli (NTEC, n = 2) from human and cattle sources to form biofilms on different surfaces, and determine whether extracellular matrix (ECM) components (cellulose, curli), motility, prophage insertion in mlrA and cell surface hydrophobicity could influence biofilm formation. Finally, the influence of biofilm formation on the sensitivity of isolates to quaternary ammonium compounds (QACs; Profoam, Kwiksan 22) and peracetic acid-based sanitizer (Topactive Des.) for 2 min on polystyrene plate were also evaluated.

RESULTS: Biofilm production on one surface may not indicate biofilm formation on a different surface. Biofilm was formed by different pathotypes on polystyrene (70%), stainless steel (87.5%) and glass slides (95%), however only 50% demonstrated pellicle formation. EHEC isolates were significantly more likely to form a pellicle at the air-liquid interface and biofilms on polystyrene surface at 48 h than aEPEC. Strains that don't produce ECM (curli or cellulose), harbor a prophage insertion in mlrA, and are non-motile have lower biofilm forming capacities than those isolates possessing combinations of these attributes. Hydrophobicity had no impact on biofilm formation. After 2 min exposure, none of the disinfectants tested were able to completely inactivate all cells within a biofilm regardless of pathotypes and the amount of biofilm formed.

CONCLUSION: Pathotypes of E. coli O26 showed varying capacities to form biofilms, however, most EHEC strains had the capacity to form biofilm on all surfaces and at the air-liquid interface under the conditions used in this study. Biofilms provided a protective effect to E. coli O26 strains against the three sanitizers, previously shown to successfully control the growth of their planktonic counterparts. Whether the characteristics of biofilm forming and non-biofilm forming strains observed in this study reflect their attributes within the food and meat-processing environments is unknown. Further studies that represent the food and meat-processing environments are required.}, } @article {pmid29739316, year = {2018}, author = {Gioia, L and Siddique, A and Head, SR and Salomon, DR and Su, AI}, title = {A genome-wide survey of mutations in the Jurkat cell line.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {334}, pmid = {29739316}, issn = {1471-2164}, support = {U19 AI063603/AI/NIAID NIH HHS/United States ; UL1 TR001114/TR/NCATS NIH HHS/United States ; U19 AI063603//National Institutes of Health/ ; UL1 TR001114//National Center for Advancing Translational Sciences/ ; }, mesh = {Databases, Genetic ; Genomic Instability/genetics ; *Genomics ; Glycosylation ; Humans ; Jurkat Cells ; *Mutation ; Receptors, Antigen, T-Cell/metabolism ; Signal Transduction/genetics ; *Whole Genome Sequencing ; }, abstract = {BACKGROUND: The Jurkat cell line has an extensive history as a model of T cell signaling. But at the turn of the 21st century, some expression irregularities were observed, raising doubts about how closely the cell line paralleled normal human T cells. While numerous expression deficiencies have been described in Jurkat, genetic explanations have only been provided for a handful of defects.

RESULTS: Here, we report a comprehensive catolog of genomic variation in the Jurkat cell line based on whole-genome sequencing. With this list of all detectable, non-reference sequences, we prioritize potentially damaging mutations by mining public databases for functional effects. We confirm documented mutations in Jurkat and propose links from detrimental gene variants to observed expression abnormalities in the cell line.

CONCLUSIONS: The Jurkat cell line harbors many mutations that are associated with cancer and contribute to Jurkat's unique characteristics. Genes with damaging mutations in the Jurkat cell line are involved in T-cell receptor signaling (PTEN, INPP5D, CTLA4, and SYK), maintenance of genome stability (TP53, BAX, and MSH2), and O-linked glycosylation (C1GALT1C1). This work ties together decades of molecular experiments and serves as a resource that will streamline both the interpretation of past research and the design of future Jurkat studies.}, } @article {pmid29739315, year = {2018}, author = {Joy, N and Maimoonath Beevi, YP and Soniya, EV}, title = {A deeper view into the significance of simple sequence repeats in pre-miRNAs provides clues for its possible roles in determining the function of microRNAs.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {29}, pmid = {29739315}, issn = {1471-2156}, support = {SR/WOS-A/LS-1380/2014(G)//Department of Science and Technology, Government of India/ ; }, abstract = {BACKGROUND: The central tenet of 'genome content' has been that the 'non-coding' parts are highly enriched with 'microsatellites' or 'Simple Sequence Repeats' (SSRs). We presume that the presence and change in number of repeat unit (n) of SSRs in different genomic locations may or may not become beneficial, depending on the position of SSRs in a gene. Very few studies have looked into the existence of SSRs in the hair-pin precursors of miRNAs (pre-miRNAs). The interplay between SSRs and miRNAs is not yet clearly understood.

RESULTS: Considering the potential significance of SSRs in pre-miRNAs, we analysed the miRNA hair-pin precursors of 171 organisms, which revealed a noticeable (29.8%) existence of SSRs in their pre-miRNAs. The maintenance of SSRs in pre-miRNAs even in the complex, highly evolved phyla like Chordata and Magnoliophyta shed light upon its diverse functions. Putative effects of SSRs in either regulating the biogenesis or function of miRNAs were more underlined based on computational and experimental analysis. A preliminary computational analysis to explore the relevance of such SSRs maintained in pre-miRNA sequences led to the detection of splicing regulatory elements (SREs) either in or near to the SSRs. The absence of SSRs correspondingly decreased the detection of SREs.

CONCLUSION: The present study is the first implication for the possible involvement of SSRs in shaping the SREs to undergo Alternative Splicing events to produce miRNA isoforms in accordance with different stress environments. This part of work well demonstrates the importance of studying such consistently maintained SSRs residing in pre-miRNAs and can enhance more and more research towards deciphering the exact function of SSRs in the near future.}, } @article {pmid29739313, year = {2018}, author = {Simpson, AG and Wagner, PJ and Wing, SL and Fenster, CB}, title = {Binary-state speciation and extinction method is conditionally robust to realistic violations of its assumptions.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {69}, pmid = {29739313}, issn = {1471-2148}, support = {NA (TAship)//University of Maryland College Park/International ; }, mesh = {*Algorithms ; Animals ; Computer Simulation ; *Extinction, Biological ; *Genetic Speciation ; Phylogeny ; Quantitative Trait, Heritable ; Time Factors ; }, abstract = {BACKGROUND: Phylogenetic comparative methods allow us to test evolutionary hypotheses without the benefit of an extensive fossil record. These methods, however, make simplifying assumptions, among them that clades are always increasing or stable in diversity, an assumption we know to be false. This study simulates hypothetical clades to test whether the Binary State Speciation and Extinction (BiSSE) method can be used to correctly detect relative differences in diversification rate between ancestral and derived character states even as net diversification rates are declining overall. We simulate clades with declining but positive diversification rates, as well those in which speciation rates decline below extinction rates so that they are losing richness for part of their history. We run these analyses both with simulated symmetric and asymmetric speciation rates to test whether BiSSE can be used to detect them correctly.

RESULTS: For simulations with a neutral character, the fit for a BiSSE model with a neutral character is better than alternative models so long as net diversification rates remain positive. Once net diversification rates become negative, the BiSSE model with the greatest likelihood often has a non-neutral character, even though there is no such character in the simulation. BiSSE's usefulness in detecting real asymmetry in speciation rates improves with clade age, even well after net diversification rates have become negative.

CONCLUSIONS: BiSSE is most useful in analyzing clades of intermediate age, before they have reached peak diversity and gone into decline. After this point, users of BiSSE risk incorrectly inferring differential evolutionary rates when none exist. Fortunately, most studies using BiSSE and similar models focus on rapid, recent diversifications, and are less likely to encounter the biases BiSSE models are subject to for older clades. For extant groups that were once more diverse than now, however, caution should be taken in inferring past diversification patterns without fossil data.}, } @article {pmid29739312, year = {2018}, author = {Li, B and Qiao, L and An, L and Wang, W and Liu, J and Ren, Y and Pan, Y and Jing, J and Liu, W}, title = {Transcriptome analysis of adipose tissues from two fat-tailed sheep breeds reveals key genes involved in fat deposition.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {338}, pmid = {29739312}, issn = {1471-2164}, support = {BJRC201203//Program for the Top Innovative Talents of Shanxi Agricultural University/ ; 31372292//National Natural Science Foundation of China/ ; }, mesh = {Adipose Tissue/*metabolism ; Animals ; *Gene Expression Profiling ; Molecular Sequence Annotation ; Sequence Analysis, RNA ; Sheep/*genetics/*metabolism ; }, abstract = {BACKGROUND: The level of fat deposition in carcass is a crucial factor influencing meat quality. Guangling Large-Tailed (GLT) and Small-Tailed Han (STH) sheep are important local Chinese fat-tailed breeds that show distinct patterns of fat depots. To gain a better understanding of fat deposition, transcriptome profiles were determined by RNA-sequencing of perirenal, subcutaneous, and tail fat tissues from both the sheep breeds. The common highly expressed genes (co-genes) in all the six tissues, and the genes that were differentially expressed (DE genes) between these two breeds in the corresponding tissues were analyzed.

RESULTS: Approximately 47 million clean reads were obtained for each sample, and a total of 17,267 genes were annotated. Of the 47 highly expressed co-genes, FABP4, ADIPOQ, FABP5, and CD36 were the four most highly transcribed genes among all the known genes related to adipose deposition. FHC, FHC-pseudogene, and ZC3H10 were also highly expressed genes and could, thus, have roles in fat deposition. A total of 2091, 4233, and 4131 DE genes were identified in the perirenal, subcutaneous, and tail fat tissues between the GLT and STH breeds, respectively. Gene Ontology (GO) analysis showed that some DE genes were associated with adipose metabolism. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis revealed that PPAR signaling pathway and ECM-receptor interaction were specifically enriched. Four genes, namely LOC101102230, PLTP, C1QTNF7, and OLR1 were up-regulated and two genes, SCD and UCP-1, were down-regulated in all the tested tissues of STH. Among the genes involved in ECM-receptor interaction, the genes encoding collagens, laminins, and integrins were quite different depending on the depots or the breeds. In STH, genes such as LAMB3, RELN, TNXB, and ITGA8, were identified to be up regulated and LAMB4 was observed to be down regulated.

CONCLUSIONS: This study unravels the complex transcriptome profiles in sheep fat tissues, highlighting the candidate genes involved in fat deposition. Further studies are needed to investigate the roles of the candidate genes in fat deposition and in determining the meat quality of sheep.}, } @article {pmid29739311, year = {2018}, author = {Sun, L and Sun, G and Shi, C and Sun, D}, title = {Transcriptome analysis reveals new microRNAs-mediated pathway involved in anther development in male sterile wheat.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {333}, pmid = {29739311}, issn = {1471-2164}, support = {2016YFD0101601//National Key Research and Development Program of China/ ; 31601294//National Natural Science Foundation of China/ ; 2015M582241//China Postdoctoral Science Foundation/ ; }, mesh = {Base Sequence ; Flowers/genetics/growth & development ; Gene Expression Profiling ; Meiosis/genetics ; MicroRNAs/chemistry/genetics/*metabolism ; Phenotype ; Plant Proteins/antagonists & inhibitors/genetics/metabolism ; RNA, Plant/chemistry/genetics/metabolism ; Sequence Alignment ; Sequence Analysis, RNA ; Transcriptome ; Triticum/*genetics/growth & development ; }, abstract = {BACKGROUND: 337S is a novel bi-pole-photo-thermo-sensitive genic male sterile line in wheat, and sensitive to both long day length/high temperature and short day length/low temperature condition. Although the regulatory function of MicroRNAs (miRNAs) in reproductive development has been increasingly studied, their roles in pre-meiotic and meiotic cells formation of plants have not been clearly explored. Here, we explored the roles of miRNAs in regulating male sterility of 337S at short day length/low temperature condition.

RESULTS: Small RNA sequencing and degradome analyses were employed to identify miRNAs and their targets in the 337S whose meiotic cells collapsed rapidly during male meiotic prophase, resulting in failure of meiosis at SL condition. A total of 102 unique miRNAs were detected. Noticeably, the largest miRNA family was MiR1122. The target CCR4-associated factor 1 (CAF1) of miR2275, a subunit of the Carbon Catabolite Repressed 4-Negative on TATA-less (CCR4-NOT) complex, contributes to the process of early meiosis, and was first identified here. Further studies showed that the expression of several pivotal anther-related miRNAs was altered in 337S at SL condition, especially tae-miR1127a, which may be related to male sterility of 337S. Here, we also identified a new member of SWI/SNF factors SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily A, member 3-like 3 (SMARCA3L3) targeted by tae-miR1127a, whose function might be involved in faithful progression of meiosis in male reproductive cells.

CONCLUSION: The miRNA-target interactions of tae-miR2275-CAF1 and tae-miR1127a-SMARCA3L3 might be involved in regulating male fertility in 337S. Our results also implied that multiple roles for SMARCA3L3 and CAF1 in DNA repair and transcriptional regulation jointly orchestrated a tight and orderly system for maintaining chromatin and genome integrity during meiosis.}, } @article {pmid29739310, year = {2018}, author = {Gu, Y and Wang, Y and Sun, Y and Zhao, K and Xiang, Q and Yu, X and Zhang, X and Chen, Q}, title = {Genetic diversity and characterization of arsenic-resistant endophytic bacteria isolated from Pteris vittata, an arsenic hyperaccumulator.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {42}, pmid = {29739310}, issn = {1471-2180}, abstract = {BACKGROUND: Alleviating arsenic (As) contamination is a high-priority environmental issue. Hyperaccumulator plants may harbor endophytic bacteria able to detoxify As. Therefore, we investigated the distribution, diversity, As (III) resistance levels, and resistance-related functional genes of arsenite-resistant bacterial endophytes in Pteris vittata L. growing in a lead-zinc mining area with different As contamination levels.

RESULTS: A total of 116 arsenite-resistant bacteria were isolated from roots of P. vittata with different As concentrations. Based on the 16S rRNA gene sequence analysis of representative isolates, the isolates belonged to Proteobacteria, Actinobacteria, and Firmicutes. Major genera found were Agrobacterium, Stenotrophomonas, Pseudomonas, Rhodococcus, and Bacillus. The most highly arsenite-resistant bacteria (minimum inhibitory concentration > 45 mM) were isolated from P. vittata with high As concentrations and belonged to the genera Agrobacterium and Bacillus. The strains with high As tolerance also showed high levels of indole-3-acetic acid (IAA) production and carried arsB/ACR3(2) genes. The arsB and ACR3(2) were most likely horizontally transferred among the strains.

CONCLUSION: The results of this study suggest that P. vittata plants with high As concentrations may select diverse arsenite-resistant bacteria; this diversity might, at least partly, be a result of horizontal gene transfer. These diverse endophytic bacteria are potential candidates to enhance phytoremediation techniques.}, } @article {pmid29738620, year = {2018}, author = {Schou, MF and Bechsgaard, J and Muñoz, J and Kristensen, TN}, title = {Genome-wide regulatory deterioration impedes adaptive responses to stress in inbred populations of Drosophila melanogaster.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13497}, pmid = {29738620}, issn = {1558-5646}, abstract = {Inbreeding depression is often intensified under environmental stress (i.e., inbreeding-stress interaction). Although the fitness consequences of this phenomenon are well-described, underlying mechanisms such as an increased expression of deleterious alleles under stress, or a lower capacity for adaptive responses to stress with inbreeding, have rarely been investigated. We investigated a fitness component (egg-to-adult viability) and gene-expression patterns using RNA-seq analyses in noninbred control lines and in inbred lines of Drosophila melanogaster exposed to benign temperature or heat stress. We find little support for an increase in the cumulative expression of deleterious alleles under stress. Instead, inbred individuals had a reduced ability to induce an adaptive gene regulatory stress response compared to controls. The decrease in egg-to-adult viability due to stress was most pronounced in the lines with the largest deviation in the adaptive stress response (R2 = 0.48). Thus, we find strong evidence for a lower capacity of inbred individuals to respond by gene regulation to stress and that this is the main driver of inbreeding-stress interactions. In comparison, the altered gene expression due to inbreeding at benign temperature showed no correlation with fitness and was pronounced in genomic regions experiencing the highest increase in homozygosity.}, } @article {pmid29737524, year = {2018}, author = {Werry, N}, title = {Digest: Survey of field-based studies identifies trends in maintenance of sex.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1328-1329}, doi = {10.1111/evo.13499}, pmid = {29737524}, issn = {1558-5646}, } @article {pmid29736999, year = {2018}, author = {Brandl, SJ and Goatley, CHR and Bellwood, DR and Tornabene, L}, title = {The hidden half: ecology and evolution of cryptobenthic fishes on coral reefs.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1846-1873}, doi = {10.1111/brv.12423}, pmid = {29736999}, issn = {1469-185X}, abstract = {Teleost fishes are the most diverse group of vertebrates on Earth. On tropical coral reefs, their species richness exceeds 6000 species; one tenth of total vertebrate biodiversity. A large proportion of this diversity is composed of cryptobenthic reef fishes (CRFs): bottom-dwelling, morphologically or behaviourally cryptic species typically less than 50 mm in length. Yet, despite their diversity and abundance, these fishes are both poorly defined and understood. Herein we provide a new quantitative definition and synthesise current knowledge on the diversity, distribution and life history of CRFs. First, we use size distributions within families to define 17 core CRF families as characterised by the high prevalence (>10%) of small-bodied species (<50 mm). This stands in strong contrast to 42 families of large reef fishes, in which virtually no small-bodied species have evolved. We posit that small body size has allowed CRFs to diversify at extremely high rates, primarily by allowing for fine partitioning of microhabitats and facilitation of allopatric reproductive isolation; yet, we are far from understanding and documenting the biodiversity of CRFs. Using rates of description since 1758, we predict that approximately 30 new species of cryptobenthic species will be described per year until 2050 (approximately twice the annual rate compared to large fishes). Furthermore, we predict that by the year 2031, more than half of the described coral reef fish biodiversity will consist of CRFs. These fishes are the 'hidden half' of vertebrate biodiversity on coral reefs. Notably, global geographic coverage and spatial resolution of quantitative data on CRF communities is uniformly poor, which further emphasises the remarkable reservoir of biodiversity that is yet to be discovered. Although small body size may have enabled extensive diversification within CRF families, small size also comes with a suite of ecological challenges that affect fishes' capacities to feed, survive and reproduce; we identify a range of life-history adaptations that have enabled CRFs to overcome these limitations. In turn, these adaptations bestow a unique socio-ecological role on CRFs, which includes a key role in coral reef trophodynamics by cycling trophic energy provided by microscopic prey to larger consumers. Although small in body size, the ecology and evolutionary history of CRFs may make them a critical component of coral-reef food webs; yet our review also shows that these fishes are highly susceptible to a variety of anthropogenic disturbances. Understanding the consequences of these changes for CRFs and coral reef ecosystems will require us to shed more light on this frequently overlooked but highly diverse and abundant guild of coral reef fishes.}, } @article {pmid29736817, year = {2018}, author = {Yoon, J and Yasumoto-Hirose, M and Kasai, H}, title = {Correction to: Coraliitalea coralii gen. nov., sp. nov., a Marine Bacterium of the Family Flavobacteriaceae Isolated from the Hard Coral Galaxea fascicularis.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1501-5}, pmid = {29736817}, issn = {1432-0991}, abstract = {In the original version of this paper, the Chemotaxonomic Characteristics in the Results and Discussion section and legend of Table 2 given in the above paper are incorrect. These errors are corrected with this erratum.}, } @article {pmid29736038, year = {2018}, author = {Tromp, AT and Van Gent, M and Abrial, P and Martin, A and Jansen, JP and De Haas, CJC and Van Kessel, KPM and Bardoel, BW and Kruse, E and Bourdonnay, E and Boettcher, M and McManus, MT and Day, CJ and Jennings, MP and Lina, G and Vandenesch, F and Van Strijp, JAG and Lebbink, RJ and Haas, PA and Henry, T and Spaan, AN}, title = {Human CD45 is an F-component-specific receptor for the staphylococcal toxin Panton-Valentine leukocidin.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {708-717}, doi = {10.1038/s41564-018-0159-x}, pmid = {29736038}, issn = {2058-5276}, abstract = {The staphylococcal bi-component leukocidins Panton-Valentine leukocidin (PVL) and γ-haemolysin CB (HlgCB) target human phagocytes. Binding of the toxins' S-components to human complement C5a receptor 1 (C5aR1) contributes to cellular tropism and human specificity of PVL and HlgCB. To investigate the role of both leukocidins during infection, we developed a human C5aR1 knock-in (hC5aR1KI) mouse model. HlgCB, but unexpectedly not PVL, contributed to increased bacterial loads in tissues of hC5aR1KI mice. Compared to humans, murine hC5aR1KI neutrophils showed a reduced sensitivity to PVL, which was mediated by the toxin's F-component LukF-PV. By performing a genome-wide CRISPR-Cas9 screen, we identified CD45 as a receptor for LukF-PV. The human-specific interaction between LukF-PV and CD45 provides a molecular explanation for resistance of hC5aR1KI mouse neutrophils to PVL and probably contributes to the lack of a PVL-mediated phenotype during infection in these mice. This study demonstrates an unsuspected role of the F-component in driving the sensitivity of human phagocytes to PVL.}, } @article {pmid29736037, year = {2018}, author = {Flyak, AI and Kuzmina, N and Murin, CD and Bryan, C and Davidson, E and Gilchuk, P and Gulka, CP and Ilinykh, PA and Shen, X and Huang, K and Ramanathan, P and Turner, H and Fusco, ML and Lampley, R and Kose, N and King, H and Sapparapu, G and Doranz, BJ and Ksiazek, TG and Wright, DW and Saphire, EO and Ward, AB and Bukreyev, A and Crowe, JE}, title = {Broadly neutralizing antibodies from human survivors target a conserved site in the Ebola virus glycoprotein HR2-MPER region.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {670-677}, pmid = {29736037}, issn = {2058-5276}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; U19 AI109711/AI/NIAID NIH HHS/United States ; R01 AI067927/AI/NIAID NIH HHS/United States ; U19 AI109762/AI/NIAID NIH HHS/United States ; HHSN272201400058C/AI/NIAID NIH HHS/United States ; UL1 RR024975/RR/NCRR NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; }, abstract = {Ebola virus (EBOV) in humans causes a severe illness with high mortality rates. Several strategies have been developed in the past to treat EBOV infection, including the antibody cocktail ZMapp, which has been shown to be effective in nonhuman primate models of infection 1 and has been used under compassionate-treatment protocols in humans 2 . ZMapp is a mixture of three chimerized murine monoclonal antibodies (mAbs)3-6 that target EBOV-specific epitopes on the surface glycoprotein7,8. However, ZMapp mAbs do not neutralize other species from the genus Ebolavirus, such as Bundibugyo virus (BDBV), Reston virus (RESTV) or Sudan virus (SUDV). Here, we describe three naturally occurring human cross-neutralizing mAbs, from BDBV survivors, that target an antigenic site in the canonical heptad repeat 2 (HR2) region near the membrane-proximal external region (MPER) of the glycoprotein. The identification of a conserved neutralizing antigenic site in the glycoprotein suggests that these mAbs could be used to design universal antibody therapeutics against diverse ebolavirus species. Furthermore, we found that immunization with a peptide comprising the HR2-MPER antigenic site elicits neutralizing antibodies in rabbits. Structural features determined by conserved residues in the antigenic site described here could inform an epitope-based vaccine design against infection caused by diverse ebolavirus species.}, } @article {pmid29736017, year = {2018}, author = {Nikolov, N and Sing, DK and Fortney, JJ and Goyal, JM and Drummond, B and Evans, TM and Gibson, NP and De Mooij, EJW and Rustamkulov, Z and Wakeford, HR and Smalley, B and Burgasser, AJ and Hellier, C and Helling, C and Mayne, NJ and Madhusudhan, N and Kataria, T and Baines, J and Carter, AL and Ballester, GE and Barstow, JK and McCleery, J and Spake, JJ}, title = {An absolute sodium abundance for a cloud-free 'hot Saturn' exoplanet.}, journal = {Nature}, volume = {557}, number = {7706}, pages = {526-529}, doi = {10.1038/s41586-018-0101-7}, pmid = {29736017}, issn = {1476-4687}, abstract = {Broad absorption signatures from alkali metals, such as the sodium (Na I) and potassium (K I) resonance doublets, have long been predicted in the optical atmospheric spectra of cloud-free irradiated gas giant exoplanets1-3. However, observations have revealed only the narrow cores of these features rather than the full pressure-broadened profiles4-6. Cloud and haze opacity at the day-night planetary terminator are considered to be responsible for obscuring the absorption-line wings, which hinders constraints on absolute atmospheric abundances7-9. Here we report an optical transmission spectrum for the 'hot Saturn' exoplanet WASP-96b obtained with the Very Large Telescope, which exhibits the complete pressure-broadened profile of the sodium absorption feature. The spectrum is in excellent agreement with cloud-free, solar-abundance models assuming chemical equilibrium. We are able to measure a precise, absolute sodium abundance of logεNa = [Formula: see text], and use it as a proxy for the planet's atmospheric metallicity relative to the solar value (Zp/Zʘ = [Formula: see text]). This result is consistent with the mass-metallicity trend observed for Solar System planets and exoplanets10-12.}, } @article {pmid29736016, year = {2018}, author = {Ma, Z and He, S and Wang, X and Sun, J and Zhang, Y and Zhang, G and Wu, L and Li, Z and Liu, Z and Sun, G and Yan, Y and Jia, Y and Yang, J and Pan, Z and Gu, Q and Li, X and Sun, Z and Dai, P and Liu, Z and Gong, W and Wu, J and Wang, M and Liu, H and Feng, K and Ke, H and Wang, J and Lan, H and Wang, G and Peng, J and Wang, N and Wang, L and Pang, B and Peng, Z and Li, R and Tian, S and Du, X}, title = {Resequencing a core collection of upland cotton identifies genomic variation and loci influencing fiber quality and yield.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {803-813}, doi = {10.1038/s41588-018-0119-7}, pmid = {29736016}, issn = {1546-1718}, abstract = {Upland cotton is the most important natural-fiber crop. The genomic variation of diverse germplasms and alleles underpinning fiber quality and yield should be extensively explored. Here, we resequenced a core collection comprising 419 accessions with 6.55-fold coverage depth and identified approximately 3.66 million SNPs for evaluating the genomic variation. We performed phenotyping across 12 environments and conducted genome-wide association study of 13 fiber-related traits. 7,383 unique SNPs were significantly associated with these traits and were located within or near 4,820 genes; more associated loci were detected for fiber quality than fiber yield, and more fiber genes were detected in the D than the A subgenome. Several previously undescribed causal genes for days to flowering, fiber length, and fiber strength were identified. Phenotypic selection for these traits increased the frequency of elite alleles during domestication and breeding. These results provide targets for molecular selection and genetic manipulation in cotton improvement.}, } @article {pmid29736015, year = {2018}, author = {Zhou, M and Palanca, AMS and Law, JA}, title = {Locus-specific control of the de novo DNA methylation pathway in Arabidopsis by the CLASSY family.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {865-873}, doi = {10.1038/s41588-018-0115-y}, pmid = {29736015}, issn = {1546-1718}, support = {R01 GM112966/GM/NIGMS NIH HHS/United States ; }, abstract = {DNA methylation is essential for gene regulation, transposon silencing and imprinting. Although the generation of specific DNA methylation patterns is critical for these processes, how methylation is regulated at individual loci remains unclear. Here we show that a family of four putative chromatin remodeling factors, CLASSY (CLSY) 1-4, are required for both locus-specific and global regulation of DNA methylation in Arabidopsis thaliana. Mechanistically, these factors act in connection with RNA polymerase-IV (Pol-IV) to control the production of 24-nucleotide small interfering RNAs (24nt-siRNAs), which guide DNA methylation. Individually, the CLSYs regulate Pol-IV-chromatin association and 24nt-siRNA production at thousands of distinct loci, and together, they regulate essentially all 24nt-siRNAs. Depending on the CLSYs involved, this regulation relies on different repressive chromatin modifications to facilitate locus-specific control of DNA methylation. Given the conservation between methylation systems in plants and mammals, analogous pathways may operate in a broad range of organisms.}, } @article {pmid29736014, year = {2018}, author = {Du, X and Huang, G and He, S and Yang, Z and Sun, G and Ma, X and Li, N and Zhang, X and Sun, J and Liu, M and Jia, Y and Pan, Z and Gong, W and Liu, Z and Zhu, H and Ma, L and Liu, F and Yang, D and Wang, F and Fan, W and Gong, Q and Peng, Z and Wang, L and Wang, X and Xu, S and Shang, H and Lu, C and Zheng, H and Huang, S and Lin, T and Zhu, Y and Li, F}, title = {Resequencing of 243 diploid cotton accessions based on an updated A genome identifies the genetic basis of key agronomic traits.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {796-802}, doi = {10.1038/s41588-018-0116-x}, pmid = {29736014}, issn = {1546-1718}, abstract = {The ancestors of Gossypium arboreum and Gossypium herbaceum provided the A subgenome for the modern cultivated allotetraploid cotton. Here, we upgraded the G. arboreum genome assembly by integrating different technologies. We resequenced 243 G. arboreum and G. herbaceum accessions to generate a map of genome variations and found that they are equally diverged from Gossypium raimondii. Independent analysis suggested that Chinese G. arboreum originated in South China and was subsequently introduced to the Yangtze and Yellow River regions. Most accessions with domestication-related traits experienced geographic isolation. Genome-wide association study (GWAS) identified 98 significant peak associations for 11 agronomically important traits in G. arboreum. A nonsynonymous substitution (cysteine-to-arginine substitution) of GaKASIII seems to confer substantial fatty acid composition (C16:0 and C16:1) changes in cotton seeds. Resistance to fusarium wilt disease is associated with activation of GaGSTF9 expression. Our work represents a major step toward understanding the evolution of the A genome of cotton.}, } @article {pmid29736013, year = {2018}, author = {Gozdecka, M and Meduri, E and Mazan, M and Tzelepis, K and Dudek, M and Knights, AJ and Pardo, M and Yu, L and Choudhary, JS and Metzakopian, E and Iyer, V and Yun, H and Park, N and Varela, I and Bautista, R and Collord, G and Dovey, O and Garyfallos, DA and De Braekeleer, E and Kondo, S and Cooper, J and Göttgens, B and Bullinger, L and Northcott, PA and Adams, D and Vassiliou, GS and Huntly, BJP}, title = {UTX-mediated enhancer and chromatin remodeling suppresses myeloid leukemogenesis through noncatalytic inverse regulation of ETS and GATA programs.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {883-894}, pmid = {29736013}, issn = {1546-1718}, abstract = {The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss. By integrating proteomic and genomic analyses, we link these changes to UTX regulation of ATP-dependent chromatin remodeling, coordination of the COMPASS complex and enhanced pioneering activity of ETS factors during evolution to AML. Collectively, our findings identify a dual role for UTX in suppressing acute myeloid leukemia via repression of oncogenic ETS and upregulation of tumor-suppressive GATA programs.}, } @article {pmid29735990, year = {2018}, author = {Somveille, M and Rodrigues, ASL and Manica, A}, title = {Energy efficiency drives the global seasonal distribution of birds.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {962-969}, doi = {10.1038/s41559-018-0556-9}, pmid = {29735990}, issn = {2397-334X}, abstract = {The uneven distribution of biodiversity on Earth is one of the most general and puzzling patterns in ecology. Many hypotheses have been proposed to explain it, based on evolutionary processes or on constraints related to geography and energy. However, previous studies investigating these hypotheses have been largely descriptive due to the logistical difficulties of conducting controlled experiments on such large geographical scales. Here, we use bird migration-the seasonal redistribution of approximately 15% of bird species across the world-as a natural experiment for testing the species-energy relationship, the hypothesis that animal diversity is driven by energetic constraints. We develop a mechanistic model of bird distributions across the world, and across seasons, based on simple ecological and energetic principles. Using this model, we show that bird species distributions optimize the balance between energy acquisition and energy expenditure while taking into account competition with other species. These findings support, and provide a mechanistic explanation for, the species-energy relationship. The findings also provide a general explanation of migration as a mechanism that allows birds to optimize their energy budget in the face of seasonality and competition. Finally, our mechanistic model provides a tool for predicting how ecosystems will respond to global anthropogenic change.}, } @article {pmid29735989, year = {2018}, author = {López-Bao, JV and Margalida, A}, title = {Slow transposition of European environmental policies.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {914}, doi = {10.1038/s41559-018-0565-8}, pmid = {29735989}, issn = {2397-334X}, } @article {pmid29735988, year = {2018}, author = {Bock, DG and Kantar, MB and Caseys, C and Matthey-Doret, R and Rieseberg, LH}, title = {Evolution of invasiveness by genetic accommodation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {991-999}, doi = {10.1038/s41559-018-0553-z}, pmid = {29735988}, issn = {2397-334X}, abstract = {Invasion success of species introduced to novel environments may be facilitated by adaptive evolution and by phenotypic plasticity. Here we investigate the independent and joint contribution of both mechanisms as drivers of invasiveness in the perennial sunflower Helianthus tuberosus. We show that invasive genotypes have multiple origins, and that invasive spread was facilitated by the repeated evolution of extreme values in a single trait, clonality. In line with genetic accommodation theory, we establish that this evolutionary transition occurred by refining a preexisting plastic response of clonality to water availability. Further, we demonstrate that under the non-drought conditions typically experienced by this plant in its introduced range, invasive spread is mediated by hybrid vigour and/or two major additive-effect loci, and that these mechanisms are complementary. Thus, in H. tuberosus, evolution of invasiveness was facilitated by phenotypic plasticity, and involved the use of multiple genetic solutions to achieve the same invasiveness trait.}, } @article {pmid29735744, year = {2018}, author = {Hardesty-Moore, M and Deinet, S and Freeman, R and Titcomb, GC and Dillon, EM and Stears, K and Klope, M and Bui, A and Orr, D and Young, HS and Kuile, AM and Hughey, LF and McCauley, DJ}, title = {Correction to 'Migration in the Anthropocene: how collective navigation, environmental system and taxonomy shape the vulnerability of migratory species'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, doi = {10.1098/rstb.2018.0210}, pmid = {29735744}, issn = {1471-2970}, } @article {pmid29735743, year = {2018}, author = {Willison, KR}, title = {The substrate specificity of eukaryotic cytosolic chaperonin CCT.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735743}, issn = {1471-2970}, abstract = {The cytosolic chaperonin CCT (chaperonin containing TCP-1) is an ATP-dependent double-ring protein machine mediating the folding of members of the eukaryotic cytoskeletal protein families. The actins and tubulins are obligate substrates of CCT because they are completely dependent on CCT activity to reach their native states. Genetic and proteomic analysis of the CCT interactome in the yeast Saccharomyces cerevisiae revealed a CCT network of approximately 300 genes and proteins involved in many fundamental biological processes. We classified network members into sets such as substrates, CCT cofactors and CCT-mediated assembly processes. Many members of the 7-bladed propeller family of proteins are commonly found tightly bound to CCT isolated from human and plant cells and yeasts. The anaphase promoting complex (APC/C) cofactor propellers, Cdh1p and Cdc20p, are also obligate substrates since they both require CCT for folding and functional activation. In vitro translation analysis in prokaryotic and eukaryotic cell extracts of a set of yeast propellers demonstrates their highly differential interactions with CCT and GroEL (another chaperonin). Individual propeller proteins have idiosyncratic interaction modes with CCT because they emerged independently with neo-functions many times throughout eukaryotic evolution. We present a toy model in which cytoskeletal protein biogenesis and folding flux through CCT couples cell growth and size control to time dependent cell cycle mechanisms.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735742, year = {2018}, author = {Garton, M and MacKinnon, SS and Malevanets, A and Wodak, SJ}, title = {Interplay of self-association and conformational flexibility in regulating protein function.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735742}, issn = {1471-2970}, abstract = {Many functional roles have been attributed to homodimers, the most common mode of protein self-association, notably in the regulation of enzymes, ion channels, transporters and transcription factors. Here we review findings that offer new insights into the different roles conformational flexibility plays in regulating homodimer function. Intertwined homodimers of two-domain proteins and their related family members display significant conformational flexibility, which translates into concerted motion between structural domains. This flexibility enables the corresponding proteins to regulate function across family members by modulating the spatial positions of key recognition surfaces of individual domains, to either maintain subunit interfaces, alter them or break them altogether, leading to a variety of functional consequences. Many proteins may exist as monomers but carry out their biological function as homodimers or higher-order oligomers. We present early evidence that in such systems homodimer formation primes the protein for its functional role. It does so by inducing elevated mobility in protein regions corresponding to the binding epitopes of functionally important ligands. In some systems this process acts as an allosteric response elicited by the self-association reaction itself. Our analysis furthermore suggests that the induced extra mobility likely facilitates ligand binding through the mechanism of conformational selection.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735741, year = {2018}, author = {Perez-Riba, A and Synakewicz, M and Itzhaki, LS}, title = {Folding cooperativity and allosteric function in the tandem-repeat protein class.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735741}, issn = {1471-2970}, abstract = {The term allostery was originally developed to describe structural changes in one binding site induced by the interaction of a partner molecule with a distant binding site, and it has been studied in depth in the field of enzymology. Here, we discuss the concept of action at a distance in relation to the folding and function of the solenoid class of tandem-repeat proteins such as tetratricopeptide repeats (TPRs) and ankyrin repeats. Distantly located repeats fold cooperatively, even though only nearest-neighbour interactions exist in these proteins. A number of repeat-protein scaffolds have been reported to display allosteric effects, transferred through the repeat array, that enable them to direct the activity of the multi-subunit enzymes within which they reside. We also highlight a recently identified group of tandem-repeat proteins, the RRPNN subclass of TPRs, recent crystal structures of which indicate that they function as allosteric switches to modulate multiple bacterial quorum-sensing mechanisms. We believe that the folding cooperativity of tandem-repeat proteins and the biophysical mechanisms that transform them into allosteric switches are intimately intertwined. This opinion piece aims to combine our understanding of the two areas and develop ideas on their common underlying principles.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735740, year = {2018}, author = {Stock, G and Hamm, P}, title = {A non-equilibrium approach to allosteric communication.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735740}, issn = {1471-2970}, abstract = {While the theory of protein folding is well developed, including concepts such as rugged energy landscape, folding funnel, etc., the same degree of understanding has not been reached for the description of the dynamics of allosteric transitions in proteins. This is not only due to the small size of the structural change upon ligand binding to an allosteric site, but also due to challenges in designing experiments that directly observe such an allosteric transition. On the basis of recent pump-probe-type experiments (Buchli et al. 2013 Proc. Natl Acad. Sci. USA110, 11 725-11 730. (doi:10.1073/pnas.1306323110)) and non-equilibrium molecular dynamics simulations (Buchenberg et al. 2017 Proc. Natl Acad. Sci. USA114, E6804-E6811. (doi:10.1073/pnas.1707694114)) studying an photoswitchable PDZ2 domain as model for an allosteric transition, we outline in this perspective how such a description of allosteric communication might look. That is, calculating the dynamical content of both experiment and simulation (which agree remarkably well with each other), we find that allosteric communication shares some properties with downhill folding, except that it is an 'order-order' transition. Discussing the multiscale and hierarchical features of the dynamics, the validity of linear response theory as well as the meaning of 'allosteric pathways', we conclude that non-equilibrium experiments and simulations are a promising way to study dynamical aspects of allostery.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735739, year = {2018}, author = {McLeish, T and Schaefer, C and von der Heydt, AC}, title = {The 'allosteron' model for entropic allostery of self-assembly.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735739}, issn = {1471-2970}, abstract = {Using the simple 'allosteron' model, we show that it is possible, in principle, to elicit pathways by which fluctuation allostery affects self-assembly of protein complexes. We treat the cases of (i) protein fibrils and nucleation, (ii) n-mer protein complexes, and (iii) weakly attractive allosteric interactions in protein-like soft nanoscale objects that can be tuned to define exclusive self-associating families.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735738, year = {2018}, author = {Modi, T and Huihui, J and Ghosh, K and Ozkan, SB}, title = {Ancient thioredoxins evolved to modern-day stability-function requirement by altering native state ensemble.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735738}, issn = {1471-2970}, abstract = {Thioredoxins (THRXs)-small globular proteins that reduce other proteins-are ubiquitous in all forms of life, from Archaea to mammals. Although ancestral thioredoxins share sequential and structural similarity with the modern-day (extant) homologues, they exhibit significantly different functional activity and stability. We investigate this puzzle by comparative studies of their (ancient and modern-day THRXs') native state ensemble, as quantified by the dynamic flexibility index (DFI), a metric for the relative resilience of an amino acid to perturbations in the rest of the protein. Clustering proteins using DFI profiles strongly resemble an alternative classification scheme based on their activity and stability. The DFI profiles of the extant proteins are substantially different around the α3, α4 helices and catalytic regions. Likewise, allosteric coupling of the active site with the rest of the protein is different between ancient and extant THRXs, possibly explaining the decreased catalytic activity at low pH with evolution. At a global level, we note that the population of low-flexibility (called hinges) and high-flexibility sites increases with evolution. The heterogeneity (quantified by the variance) in DFI distribution increases with the decrease in the melting temperature typically associated with the evolution of ancient proteins to their modern-day counterparts.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735737, year = {2018}, author = {Mayer, MP}, title = {Intra-molecular pathways of allosteric control in Hsp70s.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735737}, issn = {1471-2970}, abstract = {The 70 kDa heat-shock protein (Hsp70) is undoubtedly the most versatile of all molecular chaperones. Hsp70 is involved in numerous cellular protein folding processes, accompanying proteins throughout their lifespan from de novo folding at the ribosome to degradation at the proteasome, surveilling protein stability and functionality. Several properties of this ATP-dependent chaperone constitute the molecular basis for this versatility. With its substrate binding domain (SBD), Hsp70 transiently interacts with a short degenerative linear sequence motif found practically in all proteins and, in addition, with more folded protein conformers. Binding to polypeptides is tightly regulated by ATP binding and hydrolysis in the nucleotide binding domain, which is coupled to the SBD by an intricate allosteric mechanism. Hsp70 is regulated by a host of J-cochaperones, which act as targeting factors by regulating the ATPase activity of Hsp70 in synergism with the substrates themselves, and by several families of nucleotide exchange factors. In this review, I focus on the allosteric mechanism, which allows Hsp70s to interact with substrates with ultrahigh affinity through a non-equilibrium mode of action and summarize what mutagenesis and structural studies have taught us about the pathways and mechanics of interdomain communication.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735736, year = {2018}, author = {Thirumalai, D and Hyeon, C}, title = {Signalling networks and dynamics of allosteric transitions in bacterial chaperonin GroEL: implications for iterative annealing of misfolded proteins.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735736}, issn = {1471-2970}, abstract = {Signal transmission at the molecular level in many biological complexes occurs through allosteric transitions. Allostery describes the responses of a complex to binding of ligands at sites that are spatially well separated from the binding region. We describe the structural perturbation method, based on phonon propagation in solids, which can be used to determine the signal-transmitting allostery wiring diagram (AWD) in large but finite-sized biological complexes. Application to the bacterial chaperonin GroEL-GroES complex shows that the AWD determined from structures also drives the allosteric transitions dynamically. From both a structural and dynamical perspective these transitions are largely determined by formation and rupture of salt-bridges. The molecular description of allostery in GroEL provides insights into its function, which is quantitatively described by the iterative annealing mechanism. Remarkably, in this complex molecular machine, a deep connection is established between the structures, reaction cycle during which GroEL undergoes a sequence of allosteric transitions, and function, in a self-consistent manner.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735735, year = {2018}, author = {Tafoya, S and Bustamante, C}, title = {Molecular switch-like regulation in motor proteins.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735735}, issn = {1471-2970}, abstract = {Motor proteins are powered by nucleotide hydrolysis and exert mechanical work to carry out many fundamental biological tasks. To ensure their correct and efficient performance, the motors' activities are allosterically regulated by additional factors that enhance or suppress their NTPase activity. Here, we review two highly conserved mechanisms of ATP hydrolysis activation and repression operating in motor proteins-the glutamate switch and the arginine finger-and their associated regulatory factors. We examine the implications of these regulatory mechanisms in proteins that are formed by multiple ATPase subunits. We argue that the regulatory mechanisms employed by motor proteins display features similar to those described in small GTPases, which require external regulatory elements, such as dissociation inhibitors, exchange factors and activating proteins, to switch the protein's function 'on' and 'off'. Likewise, similar regulatory roles are taken on by the motor's substrate, additional binding factors, and even adjacent subunits in multimeric complexes. However, in motor proteins, more than one regulatory factor and the two mechanisms described here often underlie the machine's operation. Furthermore, ATPase regulation takes place throughout the motor's cycle, which enables a more complex function than the binary 'active' and 'inactive' states.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735734, year = {2018}, author = {Noshiro, D and Ando, T}, title = {Substrate protein dependence of GroEL-GroES interaction cycle revealed by high-speed atomic force microscopy imaging.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735734}, issn = {1471-2970}, abstract = {A double-ring-shaped tetradecameric GroEL complex assists proper protein folding in cooperation with the cochaperonin GroES. The dynamic GroEL-GroES interaction reflects the allosteric intra- and inter-ring communications and the chaperonin reaction. Therefore, revealing this dynamic interaction is essential to understanding the allosteric communications and the operation mechanism of GroEL. Nevertheless, how this interaction proceeds in the chaperonin cycle has long been controversial. Here, we directly image the dynamic GroEL-GroES interaction under conditions with and without foldable substrate protein using high-speed atomic force microscopy. Then, the imaging results obtained under these conditions and our previous results in the presence of unfoldable substrate are compared. The molecular movies reveal that the entire reaction pathway is highly complicated but basically identical irrespective of the substrate condition. A prominent (but moderate) difference is in the population distribution of intermediate species: symmetric GroEL : GroES2 and asymmetric GroEL : GroES1 complexes, and GroES-unbound GroEL. This difference is mainly attributed to the longer lifetime of GroEL : GroES1 complexes in the presence of foldable substrate. Moreover, the inter-ring communication, which is the basis for the alternating action of the two rings, occurs at two distinct (GroES association and dissociation) steps in the main reaction pathway, irrespective of the substrate condition.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735733, year = {2018}, author = {Lorimer, GH and Fei, X and Ye, X}, title = {The GroEL chaperonin: a protein machine with pistons driven by ATP binding and hydrolysis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735733}, issn = {1471-2970}, abstract = {In response to the binding of ATP, the two heptameric rings of the GroEL chaperonin protein interact with one another in a negatively cooperative manner. Owing to the helix dipole, the positively charged nitrogen of glycine 88 at the N-terminus of helix D binds to oxygen atoms on the β and γ phosphorus atoms of ATP. In apo-GroEL, the nucleotide-binding sites of different rings are connected to one another by the interaction of the ɛ-amino group of lysine 105 of one helix D across the twofold axis with the negatively charged carbonyl oxygen atom of alanine 109 at the C-terminus of the other helix D. Upon binding ATP, the K105-A109 salt bridge breaks and both helices move apart by approximately 3.5 Å en bloc toward the ATP. Upon hydrolysis of ATP, the helices return to their original position. The helices thus behave as pistons, their movement being driven by the binding and hydrolysis of ATP.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735732, year = {2018}, author = {Sengupta, U and Strodel, B}, title = {Markov models for the elucidation of allosteric regulation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735732}, issn = {1471-2970}, abstract = {Allosteric regulation refers to the process where the effect of binding of a ligand at one site of a protein is transmitted to another, often distant, functional site. In recent years, it has been demonstrated that allosteric mechanisms can be understood by the conformational ensembles of a protein. Molecular dynamics (MD) simulations are often used for the study of protein allostery as they provide an atomistic view of the dynamics of a protein. However, given the wealth of detailed information hidden in MD data, one has to apply a method that allows extraction of the conformational ensembles underlying allosteric regulation from these data. Markov state models are one of the most promising methods for this purpose. We provide a short introduction to the theory of Markov state models and review their application to various examples of protein allostery studied by MD simulations. We also include a discussion of studies where Markov modelling has been employed to analyse experimental data on allosteric regulation. We conclude our review by advertising the wider application of Markov state models to elucidate allosteric mechanisms, especially since in recent years it has become straightforward to construct such models thanks to software programs like PyEMMA and MSMBuilder.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735731, year = {2018}, author = {Ponzoni, L and Zhang, S and Cheng, MH and Bahar, I}, title = {Shared dynamics of LeuT superfamily members and allosteric differentiation by structural irregularities and multimerization.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735731}, issn = {1471-2970}, support = {P30 DA035778/DA/NIDA NIH HHS/United States ; P41 GM103712/GM/NIGMS NIH HHS/United States ; }, abstract = {The LeuT-fold superfamily includes secondary active transporters from different functional families, which share a common tertiary structure, despite having a remarkably low sequence similarity. By identifying the common structural and dynamical features upon principal component analysis of a comprehensive ensemble of 90 experimentally resolved structures and anisotropic network model evaluation of collective motions, we provide a unified point of view for understanding the reasons why this particular fold has been selected by evolution to accomplish such a broad spectrum of functions. The parallel identification of conserved sequence features, localized at specific sites of transmembrane helices, sheds light on the role of broken helices (TM1 and TM6 in LeuT) in promoting ion/substrate binding and allosteric interconversion between the outward- and inward-facing conformations of transporters. Finally, the determination of the dynamics landscape for the structural ensemble provides a promising framework for the classification of transporters based on their dynamics, and the characterization of the collective movements that favour multimerization.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735730, year = {2018}, author = {Gruber, R and Horovitz, A}, title = {Unpicking allosteric mechanisms of homo-oligomeric proteins by determining their successive ligand binding constants.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735730}, issn = {1471-2970}, abstract = {Advances in native mass spectrometry and single-molecule techniques have made it possible in recent years to determine the values of successive ligand binding constants for large multi-subunit proteins. Given these values, it is possible to distinguish between different allosteric mechanisms and, thus, obtain insights into how various bio-molecular machines work. Here, we describe for ring-shaped homo-oligomers, in particular, how the relationship between the values of successive ligand binding constants is diagnostic for concerted, sequential and probabilistic allosteric mechanisms.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735729, year = {2018}, author = {White, JT and Li, J and Grasso, E and Wrabl, JO and Hilser, VJ}, title = {Ensemble allosteric model: energetic frustration within the intrinsically disordered glucocorticoid receptor.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735729}, issn = {1471-2970}, abstract = {Allostery is an important regulatory phenomenon enabling precise control of biological function. Initial understanding of allostery was gained from seminal work on conformational changes exhibited by structured proteins. Within the last decade, protein allostery has also been demonstrated to occur within intrinsically disordered proteins. This emerging concept of disorder-mediated allostery can be usefully understood in the context of a thermodynamic ensemble. The advantage of this ensemble allosteric model is that it unifies the explanations of allostery occurring within both structured and disordered proteins. One central finding from this model is that energetic coupling, the transmission of a signal between separate regions (or domains) of a protein, is maximized when one or more domains are disordered. This is due to a disorder-order transition that contributes additional coupling energy to the allosteric system through formation of a molecular interaction surface or interface. A second key finding is that multiple interfaces may constructively or destructively interfere with each other, resulting in a new form of allosteric regulation called 'energetic frustration'. Articulating protein allostery in terms of the thermodynamic ensemble permits formulation of experimentally testable hypotheses which can increase fundamental understanding and direct drug-design efforts. These ideas are illustrated here with the specific case of human glucocorticoid receptor, a medically important multi-domain allosteric protein that contains both structured and disordered regions and exemplifies 'energetic frustration'.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735728, year = {2018}, author = {Changeux, JP}, title = {The nicotinic acetylcholine receptor: a typical 'allosteric machine'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735728}, issn = {1471-2970}, abstract = {The concept of allosteric interaction was initially proposed to account for the inhibitory feedback mechanism mediated by bacterial regulatory enzymes. In contrast with the classical mechanism of competitive, steric, interaction between ligands for a common site, allosteric interactions take place between topographically distinct sites and are mediated by a discrete and reversible conformational change of the protein. The concept was soon extended to membrane receptors for neurotransmitters and shown to apply to the signal transduction process which, in the case of the acetylcholine nicotinic receptor (nAChR), links the ACh binding site to the ion channel. Pharmacological effectors, referred to as allosteric modulators, such as Ca2+ ions and ivermectin, were discovered that enhance the transduction process when they bind to sites distinct from the orthosteric ACh site and the ion channel. The recent X-ray and electron microscopy structures, at atomic resolution, of the resting and active conformations of several homologues of the nAChR, in combination with atomistic molecular dynamics simulations reveal a stepwise quaternary transition in the transduction process with tertiary changes modifying the boundaries between subunits. These interfaces host orthosteric and allosteric modulatory sites which structural organization changes in the course of the transition. The nAChR appears as a typical allosteric machine. The model emerging from these studies has led to the conception and development of several new pharmacological agents.This article is part of a discussion meeting issue 'Allostery and molecular machines'.}, } @article {pmid29735727, year = {2018}, author = {Lorimer, GH and Horovitz, A and McLeish, T}, title = {Allostery and molecular machines.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1749}, pages = {}, pmid = {29735727}, issn = {1471-2970}, } @article {pmid29735718, year = {2018}, author = {Leftwich, PT and Clarke, NVE and Hutchings, MI and Chapman, T}, title = {Reply to Obadia et al.: Effect of methyl paraben on host-microbiota interactions in Drosophila melanogaster.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4549-E4550}, pmid = {29735718}, issn = {1091-6490}, mesh = {Animals ; *Drosophila melanogaster ; Gastrointestinal Tract ; Microbiota ; *Parabens ; }, } @article {pmid29735717, year = {2018}, author = {Roy, B and Venkatachalapathy, S and Ratna, P and Wang, Y and Jokhun, DS and Nagarajan, M and Shivashankar, GV}, title = {Laterally confined growth of cells induces nuclear reprogramming in the absence of exogenous biochemical factors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4741-E4750}, pmid = {29735717}, issn = {1091-6490}, mesh = {Animals ; Breast Neoplasms/*genetics ; *Cell Lineage ; Cell Transdifferentiation ; *Cellular Reprogramming ; Chromatin/*genetics ; Epigenesis, Genetic ; Female ; High-Throughput Nucleotide Sequencing ; Induced Pluripotent Stem Cells/*cytology/physiology ; Mice ; NIH 3T3 Cells ; *Transcriptome ; Tumor Cells, Cultured ; }, abstract = {Cells in tissues undergo transdifferentiation programs when stimulated by specific mechanical and biochemical signals. While seminal studies have demonstrated that exogenous biochemical factors can reprogram somatic cells into pluripotent stem cells, the critical roles played by mechanical signals in such reprogramming process have not been well documented. In this paper, we show that laterally confined growth of fibroblasts on micropatterned substrates induces nuclear reprogramming with high efficiency in the absence of any exogenous reprogramming factors. We provide compelling evidence on the induction of stem cell-like properties using alkaline phosphatase assays and expression of pluripotent markers. Early onset of reprogramming was accompanied with enhanced nuclear dynamics and changes in chromosome intermingling degrees, potentially facilitating rewiring of the genome. Time-lapse analysis of promoter occupancy by immunoprecipitation of H3K9Ac chromatin fragments revealed that epithelial, proliferative, and reprogramming gene promoters were progressively acetylated, while mesenchymal promoters were deacetylated by 10 days. Consistently, RNA sequencing analysis showed a systematic progression from mesenchymal to stem cell transcriptome, highlighting pathways involving mechanisms underlying nuclear reprogramming. We then demonstrated that these mechanically reprogrammed cells could be maintained as stem cells and can be redifferentiated into multiple lineages with high efficiency. Importantly, we also demonstrate the induction of cancer stemness properties in MCF7 cells grown in such laterally confined conditions. Collectively, our results highlight an important generic property of somatic cells that, when grown in laterally confined conditions, acquire stemness. Such mechanical reprogramming of somatic cells demonstrated here has important implications in tissue regeneration and disease models.}, } @article {pmid29735716, year = {2018}, author = {Champer, J and Liu, J and Oh, SY and Reeves, R and Luthra, A and Oakes, N and Clark, AG and Messer, PW}, title = {Reducing resistance allele formation in CRISPR gene drive.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5522-5527}, pmid = {29735716}, issn = {1091-6490}, support = {F32 AI138476/AI/NIAID NIH HHS/United States ; R21 AI130635/AI/NIAID NIH HHS/United States ; }, mesh = {Alleles ; Animals ; CRISPR-Cas Systems/*genetics ; Disease Resistance/*genetics ; Drosophila Proteins/*genetics ; Drosophila melanogaster/*genetics ; *Gene Drive Technology ; Genetics, Population ; Germ Cells ; Mutation ; RNA, Guide/*genetics ; RNA-Binding Proteins ; }, abstract = {CRISPR homing gene drives can convert heterozygous cells with one copy of the drive allele into homozygotes, thereby enabling super-Mendelian inheritance. Such a mechanism could be used, for example, to rapidly disseminate a genetic payload in a population, promising effective strategies for the control of vector-borne diseases. However, all CRISPR homing gene drives studied in insects thus far have produced significant quantities of resistance alleles that would limit their spread. In this study, we provide an experimental demonstration that multiplexing of guide RNAs can both significantly increase the drive conversion efficiency and reduce germline resistance rates of a CRISPR homing gene drive in Drosophila melanogaster We further show that an autosomal drive can achieve drive conversion in the male germline, with no subsequent formation of resistance alleles in embryos through paternal carryover of Cas9. Finally, we find that the nanos promoter significantly lowers somatic Cas9 expression compared with the vasa promoter, suggesting that nanos provides a superior choice in drive strategies where gene disruption in somatic cells could have fitness costs. Comparison of drive parameters among the different constructs developed in this study and a previous study suggests that, while drive conversion and germline resistance rates are similar between different genomic targets, embryo resistance rates can vary significantly. Taken together, our results mark an important step toward developing effective gene drives capable of functioning in natural populations and provide several possible avenues for further control of resistance rates.}, } @article {pmid29735715, year = {2018}, author = {Harris, A and Siggers, P and Corrochano, S and Warr, N and Sagar, D and Grimes, DT and Suzuki, M and Burdine, RD and Cong, F and Koo, BK and Clevers, H and Stévant, I and Nef, S and Wells, S and Brauner, R and Ben Rhouma, B and Belguith, N and Eozenou, C and Bignon-Topalovic, J and Bashamboo, A and McElreavey, K and Greenfield, A}, title = {ZNRF3 functions in mammalian sex determination by inhibiting canonical WNT signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5474-5479}, pmid = {29735715}, issn = {1091-6490}, support = {K99 AR070905/AR/NIAMS NIH HHS/United States ; R01 HD048584/HD/NICHD NIH HHS/United States ; MC_U142684167//Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; Adult ; Animals ; Cells, Cultured ; Disorders of Sex Development/*genetics/pathology ; Embryo, Nonmammalian/cytology/metabolism ; Female ; Gene Expression Regulation, Developmental ; Gonads/metabolism/pathology ; Humans ; Male ; Mice ; Mutation, Missense ; SOX9 Transcription Factor/genetics/metabolism ; *Sex Differentiation ; Testis/metabolism/pathology ; Thrombospondins/genetics/metabolism ; Ubiquitin-Protein Ligases/*genetics/*physiology ; Wnt Proteins/*antagonists & inhibitors/genetics/metabolism ; Young Adult ; Zebrafish ; beta Catenin/*antagonists & inhibitors/genetics/metabolism ; }, abstract = {Mammalian sex determination is controlled by the antagonistic interactions of two genetic pathways: The SRY-SOX9-FGF9 network promotes testis determination partly by opposing proovarian pathways, while RSPO1/WNT-β-catenin/FOXL2 signals control ovary development by inhibiting SRY-SOX9-FGF9. The molecular basis of this mutual antagonism is unclear. Here we show that ZNRF3, a WNT signaling antagonist and direct target of RSPO1-mediated inhibition, is required for sex determination in mice. XY mice lacking ZNRF3 exhibit complete or partial gonadal sex reversal, or related defects. These abnormalities are associated with ectopic WNT/β-catenin activity and reduced Sox9 expression during fetal sex determination. Using exome sequencing of individuals with 46,XY disorders of sex development, we identified three human ZNRF3 variants in very rare cases of XY female presentation. We tested two missense variants and show that these disrupt ZNRF3 activity in both human cell lines and zebrafish embryo assays. Our data identify a testis-determining function for ZNRF3 and indicate a mechanism of direct molecular interaction between two mutually antagonistic organogenetic pathways.}, } @article {pmid29735714, year = {2018}, author = {Singh, D and Mallon, J and Poddar, A and Wang, Y and Tippana, R and Yang, O and Bailey, S and Ha, T}, title = {Real-time observation of DNA target interrogation and product release by the RNA-guided endonuclease CRISPR Cpf1 (Cas12a).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5444-5449}, pmid = {29735714}, issn = {1091-6490}, support = {R01 GM065367/GM/NIGMS NIH HHS/United States ; R01 GM097330/GM/NIGMS NIH HHS/United States ; R01 GM112659/GM/NIGMS NIH HHS/United States ; T32 GM080189/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Acidaminococcus/*enzymology ; Bacterial Proteins/chemistry/*genetics/metabolism ; Clustered Regularly Interspaced Short Palindromic Repeats/*genetics ; DNA Cleavage ; DNA, Bacterial/chemistry/*genetics/metabolism ; DNA, Single-Stranded/chemistry/*genetics/metabolism ; Endonucleases/chemistry/*genetics/metabolism ; Genome, Bacterial ; Models, Molecular ; Nucleic Acid Conformation ; Protein Binding ; RNA, Bacterial/chemistry/*genetics/metabolism ; RNA, Guide/chemistry/*genetics/metabolism ; }, abstract = {CRISPR-Cas9, which imparts adaptive immunity against foreign genomic invaders in certain prokaryotes, has been repurposed for genome-engineering applications. More recently, another RNA-guided CRISPR endonuclease called Cpf1 (also known as Cas12a) was identified and is also being repurposed. Little is known about the kinetics and mechanism of Cpf1 DNA interaction and how sequence mismatches between the DNA target and guide-RNA influence this interaction. We used single-molecule fluorescence analysis and biochemical assays to characterize DNA interrogation, cleavage, and product release by three Cpf1 orthologs. Our Cpf1 data are consistent with the DNA interrogation mechanism proposed for Cas9. They both bind any DNA in search of protospacer-adjacent motif (PAM) sequences, verify the target sequence directionally from the PAM-proximal end, and rapidly reject any targets that lack a PAM or that are poorly matched with the guide-RNA. Unlike Cas9, which requires 9 bp for stable binding and ∼16 bp for cleavage, Cpf1 requires an ∼17-bp sequence match for both stable binding and cleavage. Unlike Cas9, which does not release the DNA cleavage products, Cpf1 rapidly releases the PAM-distal cleavage product, but not the PAM-proximal product. Solution pH, reducing conditions, and 5' guanine in guide-RNA differentially affected different Cpf1 orthologs. Our findings have important implications on Cpf1-based genome engineering and manipulation applications.}, } @article {pmid29735713, year = {2018}, author = {Chen, YC and Holmes, EC and Rajniak, J and Kim, JG and Tang, S and Fischer, CR and Mudgett, MB and Sattely, ES}, title = {N-hydroxy-pipecolic acid is a mobile metabolite that induces systemic disease resistance in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4920-E4929}, pmid = {29735713}, issn = {1091-6490}, support = {DP2 AT008321/AT/NCCIH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/growth & development/*immunology/metabolism/microbiology ; Arabidopsis Proteins/genetics/metabolism ; Disease Resistance/*immunology ; Gene Expression Regulation, Plant ; *Metabolomics ; Pipecolic Acids/*metabolism ; Plant Diseases/*immunology/microbiology ; Plant Leaves/growth & development/*immunology/metabolism/microbiology ; Pseudomonas syringae/*pathogenicity ; Signal Transduction ; }, abstract = {Systemic acquired resistance (SAR) is a global response in plants induced at the site of infection that leads to long-lasting and broad-spectrum disease resistance at distal, uninfected tissues. Despite the importance of this priming mechanism, the identity and complexity of defense signals that are required to initiate SAR signaling is not well understood. In this paper, we describe a metabolite, N-hydroxy-pipecolic acid (N-OH-Pip) and provide evidence that this mobile molecule plays a role in initiating SAR signal transduction in Arabidopsis thaliana We demonstrate that FLAVIN-DEPENDENT MONOOXYGENASE 1 (FMO1), a key regulator of SAR-associated defense priming, can synthesize N-OH-Pip from pipecolic acid in planta, and exogenously applied N-OH-Pip moves systemically in Arabidopsis and can rescue the SAR-deficiency of fmo1 mutants. We also demonstrate that N-OH-Pip treatment causes systemic changes in the expression of pathogenesis-related genes and metabolic pathways throughout the plant and enhances resistance to a bacterial pathogen. This work provides insight into the chemical nature of a signal for SAR and also suggests that the N-OH-Pip pathway is a promising target for metabolic engineering to enhance disease resistance.}, } @article {pmid29735712, year = {2018}, author = {Mitrano, M and Husain, AA and Vig, S and Kogar, A and Rak, MS and Rubeck, SI and Schmalian, J and Uchoa, B and Schneeloch, J and Zhong, R and Gu, GD and Abbamonte, P}, title = {Anomalous density fluctuations in a strange metal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5392-5396}, pmid = {29735712}, issn = {1091-6490}, abstract = {A central mystery in high-temperature superconductivity is the origin of the so-called strange metal (i.e., the anomalous conductor from which superconductivity emerges at low temperature). Measuring the dynamic charge response of the copper oxides, [Formula: see text], would directly reveal the collective properties of the strange metal, but it has never been possible to measure this quantity with millielectronvolt resolution. Here, we present a measurement of [Formula: see text] for a cuprate, optimally doped Bi2.1Sr1.9CaCu2O8+x (Tc = 91 K), using momentum-resolved inelastic electron scattering. In the medium energy range 0.1-2 eV relevant to the strange metal, the spectra are dominated by a featureless, temperature- and momentum-independent continuum persisting to the electronvolt energy scale. This continuum displays a simple power-law form, exhibiting q2 behavior at low energy and q2/ω2 behavior at high energy. Measurements of an overdoped crystal (Tc = 50 K) showed the emergence of a gap-like feature at low temperature, indicating deviation from power law form outside the strange-metal regime. Our study suggests the strange metal exhibits a new type of charge dynamics in which excitations are local to such a degree that space and time axes are decoupled.}, } @article {pmid29735711, year = {2018}, author = {Helassa, N and Dürst, CD and Coates, C and Kerruth, S and Arif, U and Schulze, C and Wiegert, JS and Geeves, M and Oertner, TG and Török, K}, title = {Ultrafast glutamate sensors resolve high-frequency release at Schaffer collateral synapses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5594-5599}, doi = {10.1073/pnas.1720648115}, pmid = {29735711}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 094385/Z/10/Z//Wellcome Trust/United Kingdom ; BB/M02556X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Glutamic Acid/*metabolism ; Hippocampus/*physiology ; Male ; Neuronal Plasticity ; Patch-Clamp Techniques ; Presynaptic Terminals/*physiology ; Pyramidal Cells/*physiology ; Rats ; Rats, Wistar ; Synapses/*physiology ; Synaptic Transmission/*physiology ; }, abstract = {Glutamatergic synapses display a rich repertoire of plasticity mechanisms on many different time scales, involving dynamic changes in the efficacy of transmitter release as well as changes in the number and function of postsynaptic glutamate receptors. The genetically encoded glutamate sensor iGluSnFR enables visualization of glutamate release from presynaptic terminals at frequencies up to ∼10 Hz. However, to resolve glutamate dynamics during high-frequency bursts, faster indicators are required. Here, we report the development of fast (iGlu f) and ultrafast (iGlu u) variants with comparable brightness but increased Kd for glutamate (137 μM and 600 μM, respectively). Compared with iGluSnFR, iGlu u has a sixfold faster dissociation rate in vitro and fivefold faster kinetics in synapses. Fitting a three-state model to kinetic data, we identify the large conformational change after glutamate binding as the rate-limiting step. In rat hippocampal slice culture stimulated at 100 Hz, we find that iGlu u is sufficiently fast to resolve individual glutamate release events, revealing that glutamate is rapidly cleared from the synaptic cleft. Depression of iGlu u responses during 100-Hz trains correlates with depression of postsynaptic EPSPs, indicating that depression during high-frequency stimulation is purely presynaptic in origin. At individual boutons, the recovery from depression could be predicted from the amount of glutamate released on the second pulse (paired pulse facilitation/depression), demonstrating differential frequency-dependent filtering of spike trains at Schaffer collateral boutons.}, } @article {pmid29735710, year = {2018}, author = {Kim, HJ and Park, JH and Kim, J and Kim, JJ and Hong, S and Kim, J and Kim, JH and Woo, HR and Hyeon, C and Lim, PO and Nam, HG and Hwang, D}, title = {Time-evolving genetic networks reveal a NAC troika that negatively regulates leaf senescence in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4930-E4939}, pmid = {29735710}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins/genetics/metabolism ; *Cellular Senescence ; Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; Mutation ; Phenotype ; Plant Development ; Plant Leaves/genetics/*growth & development ; Repressor Proteins/genetics/metabolism ; Time Factors ; Transcriptome ; }, abstract = {Senescence is controlled by time-evolving networks that describe the temporal transition of interactions among senescence regulators. Here, we present time-evolving networks for NAM/ATAF/CUC (NAC) transcription factors in Arabidopsis during leaf aging. The most evident characteristic of these time-dependent networks was a shift from positive to negative regulation among NACs at a presenescent stage. ANAC017, ANAC082, and ANAC090, referred to as a "NAC troika," govern the positive-to-negative regulatory shift. Knockout of the NAC troika accelerated senescence and the induction of other NACs, whereas overexpression of the NAC troika had the opposite effects. Transcriptome and molecular analyses revealed shared suppression of senescence-promoting processes by the NAC troika, including salicylic acid (SA) and reactive oxygen species (ROS) responses, but with predominant regulation of SA and ROS responses by ANAC090 and ANAC017, respectively. Our time-evolving networks provide a unique regulatory module of presenescent repressors that direct the timely induction of senescence-promoting processes at the presenescent stage of leaf aging.}, } @article {pmid29735709, year = {2018}, author = {Zhang, G and Baidin, V and Pahil, KS and Moison, E and Tomasek, D and Ramadoss, NS and Chatterjee, AK and McNamara, CW and Young, TS and Schultz, PG and Meredith, TC and Kahne, D}, title = {Cell-based screen for discovering lipopolysaccharide biogenesis inhibitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6834-6839}, pmid = {29735709}, issn = {1091-6490}, support = {R01 AI081059/AI/NIAID NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/*antagonists & inhibitors/genetics/metabolism ; Acinetobacter baumannii/genetics/*metabolism ; Anti-Bacterial Agents/*chemistry/*pharmacology ; Bacterial Proteins/*antagonists & inhibitors/genetics/metabolism ; Lipopolysaccharides/*biosynthesis/genetics ; }, abstract = {New drugs are needed to treat gram-negative bacterial infections. These bacteria are protected by an outer membrane which prevents many antibiotics from reaching their cellular targets. The outer leaflet of the outer membrane contains LPS, which is responsible for creating this permeability barrier. Interfering with LPS biogenesis affects bacterial viability. We developed a cell-based screen that identifies inhibitors of LPS biosynthesis and transport by exploiting the nonessentiality of this pathway in Acinetobacter We used this screen to find an inhibitor of MsbA, an ATP-dependent flippase that translocates LPS across the inner membrane. Treatment with the inhibitor caused mislocalization of LPS to the cell interior. The discovery of an MsbA inhibitor, which is universally conserved in all gram-negative bacteria, validates MsbA as an antibacterial target. Because our cell-based screen reports on the function of the entire LPS biogenesis pathway, it could be used to identify compounds that inhibit other targets in the pathway, which can provide insights into vulnerabilities of the gram-negative cell envelope.}, } @article {pmid29735708, year = {2018}, author = {Herman-Bausier, P and Labate, C and Towell, AM and Derclaye, S and Geoghegan, JA and Dufrêne, YF}, title = {Staphylococcus aureus clumping factor A is a force-sensitive molecular switch that activates bacterial adhesion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5564-5569}, doi = {10.1073/pnas.1718104115}, pmid = {29735708}, issn = {1091-6490}, mesh = {Bacterial Adhesion/*physiology ; Binding Sites ; Biomechanical Phenomena ; Cells, Cultured ; Coagulase/genetics/*metabolism ; Fibrinogen/genetics/*metabolism ; Molecular Dynamics Simulation ; Protein Binding ; Staphylococcal Infections/*microbiology ; Staphylococcus aureus/*physiology ; }, abstract = {Clumping factor A (ClfA), a cell-wall-anchored protein from Staphylococcus aureus, is a virulence factor in various infections and facilitates the colonization of protein-coated biomaterials. ClfA promotes bacterial adhesion to the blood plasma protein fibrinogen (Fg) via molecular forces that have not been studied so far. A unique, yet poorly understood, feature of ClfA is its ability to favor adhesion to Fg at high shear stress. Unraveling the strength and dynamics of the ClfA-Fg interaction would help us better understand how S. aureus colonizes implanted devices and withstands physiological shear stress. By means of single-molecule experiments, we show that ClfA behaves as a force-sensitive molecular switch that potentiates staphylococcal adhesion under mechanical stress. The bond between ClfA and immobilized Fg is weak (∼0.1 nN) at low tensile force, but is dramatically enhanced (∼1.5 nN) by mechanical tension, as observed with catch bonds. Strong bonds, but not weak ones, are inhibited by a peptide mimicking the C-terminal segment of the Fg γ-chain. These results point to a model whereby ClfA interacts with Fg via two distinct binding sites, the adhesive function of which is regulated by mechanical tension. This force-activated mechanism is of biological significance because it explains at the molecular level the ability of ClfA to promote bacterial attachment under high physiological shear stress.}, } @article {pmid29735707, year = {2018}, author = {Chapman, PD and Burkland, R and Bradley, SP and Houot, B and Bullman, V and Dacks, AM and Daly, KC}, title = {Flight motor networks modulate primary olfactory processing in the moth Manduca sexta.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5588-5593}, pmid = {29735707}, issn = {1091-6490}, support = {R01 DC009417/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; *Flight, Animal ; Histamine/*pharmacology ; Manduca ; Olfactory Bulb/cytology/drug effects/physiology ; Olfactory Pathways/drug effects/*physiology ; Olfactory Receptor Neurons/cytology/drug effects/*physiology ; Wings, Animal/drug effects/*physiology ; }, abstract = {Nervous systems must distinguish sensory signals derived from an animal's own movements (reafference) from environmentally derived sources (exafference). To accomplish this, motor networks producing reafference transmit motor information, via a corollary discharge circuit (CDC), to affected sensory networks, modulating sensory function during behavior. While CDCs have been described in most sensory modalities, none have been observed projecting to an olfactory pathway. In moths, two mesothoracic to deutocerebral histaminergic neurons (MDHns) project from flight sensorimotor centers in the mesothoracic neuromere to the antennal lobe (AL), where they provide the sole source of histamine (HA), but whether they represent a CDC is unknown. We demonstrate that MDHn spiking activity is positively correlated with wing-motor output and increased before bouts of motor activity, suggesting that MDHns communicate global locomotor state, rather than providing a precisely timed motor copy. Within the AL, HA application sharpened entrainment of projection neuron responses to odor stimuli embedded within simulated wing-beat-induced flows, whereas MDHn axotomy or AL HA receptor (HA-r) blockade reduced entrainment. This finding is consistent with higher-order CDCs, as the MDHns enhanced rather than filtered entrainment of AL projection neurons. Finally, HA-r blockade increased odor detection and discrimination thresholds in behavior assays. These results establish MDHns as a CDC that modulates AL temporal resolution, enhancing odor-guided behavior. MDHns thus appear to represent a higher-order CDC to an insect olfactory pathway; this CDC's unique nature highlights the importance of motor-to-sensory signaling as a context-specific mechanism that fine-tunes sensory function.}, } @article {pmid29735706, year = {2018}, author = {Lucas, ER and Keller, L}, title = {New explanation for the longevity of social insect reproductives: Transposable element activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5317-5318}, pmid = {29735706}, issn = {1091-6490}, mesh = {Animals ; *DNA Transposable Elements ; Genes, Insect ; Insecta ; *Longevity ; Reproduction ; }, } @article {pmid29735705, year = {2018}, author = {Sepela, RJ and Sack, JT}, title = {Taming unruly chloride channel inhibitors with rational design.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5311-5313}, doi = {10.1073/pnas.1805589115}, pmid = {29735705}, issn = {1091-6490}, support = {R01 HL128537/HL/NHLBI NIH HHS/United States ; R01 NS096317/NS/NINDS NIH HHS/United States ; T32 GM007377/GM/NIGMS NIH HHS/United States ; }, mesh = {*Chloride Channels ; }, } @article {pmid29735704, year = {2018}, author = {Nguyen, M and Krainc, D}, title = {LRRK2 phosphorylation of auxilin mediates synaptic defects in dopaminergic neurons from patients with Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5576-5581}, doi = {10.1073/pnas.1717590115}, pmid = {29735704}, issn = {1091-6490}, support = {T32 AG020506/AG/NIA NIH HHS/United States ; R01 NS076054/NS/NINDS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; P30 NS081774/NS/NINDS NIH HHS/United States ; R01 NS096240/NS/NINDS NIH HHS/United States ; }, mesh = {Auxilins/genetics/*metabolism ; Cells, Cultured ; Dopamine/*pharmacology ; Dopamine Agents/pharmacology ; Dopaminergic Neurons/metabolism/*pathology ; Endocytosis/drug effects ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics/*metabolism ; *Mutation ; Parkinson Disease/genetics/metabolism/*pathology ; Phosphorylation ; Synaptic Vesicles/metabolism/*pathology ; }, abstract = {Recently identified Parkinson's disease (PD) genes involved in synaptic vesicle endocytosis, such as DNAJC6 (auxilin), have further implicated synaptic dysfunction in PD pathogenesis. However, how synaptic dysfunction contributes to the vulnerability of human dopaminergic neurons has not been previously explored. Here, we demonstrate that commonly mutated, PD-linked leucine-rich repeat kinase 2 (LRRK2) mediates the phosphorylation of auxilin in its clathrin-binding domain at Ser627. Kinase activity-dependent LRRK2 phosphorylation of auxilin led to differential clathrin binding, resulting in disrupted synaptic vesicle endocytosis and decreased synaptic vesicle density in LRRK2 patient-derived dopaminergic neurons. Moreover, impaired synaptic vesicle endocytosis contributed to the accumulation of oxidized dopamine that in turn mediated pathogenic effects such as decreased glucocerebrosidase activity and increased α-synuclein in mutant LRRK2 neurons. Importantly, these pathogenic phenotypes were partially attenuated by restoring auxilin function in mutant LRRK2 dopaminergic neurons. Together, this work suggests that mutant LRRK2 disrupts synaptic vesicle endocytosis, leading to altered dopamine metabolism and dopamine-mediated toxic effects in patient-derived dopaminergic neurons.}, } @article {pmid29735703, year = {2018}, author = {}, title = {Correction for Martin-Sanchez et al., TWEAK and RIPK1 mediate a second wave of cell death during AKI.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4731}, doi = {10.1073/pnas.1806694115}, pmid = {29735703}, issn = {1091-6490}, } @article {pmid29735702, year = {2018}, author = {Chung, J and Zhang, X and Collins, B and Sper, RB and Gleason, K and Simpson, S and Koh, S and Sommer, J and Flowers, WL and Petters, RM and Piedrahita, JA}, title = {High mobility group A2 (HMGA2) deficiency in pigs leads to dwarfism, abnormal fetal resource allocation, and cryptorchidism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5420-5425}, pmid = {29735702}, issn = {1091-6490}, support = {R21 OD010553/OD/NIH HHS/United States ; }, mesh = {Animals ; Cryptorchidism/*etiology/pathology ; Dwarfism/*etiology/pathology ; Female ; Fetal Diseases/*etiology/pathology ; Genotype ; HMGA2 Protein/*deficiency/genetics ; Litter Size ; Male ; Nuclear Transfer Techniques/veterinary ; Pregnancy ; Reproduction ; Swine ; Swine Diseases/*etiology/pathology ; }, abstract = {Expression of HMGA2 is strongly associated with body size and growth in mice and humans. In mice, inactivation of one or both alleles of Hmga2 results in body-size reductions of 20% and 60%, respectively. In humans, microdeletions involving the HMGA2 locus result in short stature, suggesting the function of the HMGA2 protein is conserved among mammals. To test this hypothesis, we generated HMGA2-deficient pigs via gene editing and somatic cell nuclear transfer (SCNT). Examination of growth parameters revealed that HMGA2-/+ male and female pigs were on average 20% lighter and smaller than HMGA2+/+ matched controls (P < 0.05). HMGA2-/- boars showed significant size reduction ranging from 35 to 85% of controls depending on age (P < 0.05), and organ weights were also affected (P < 0.05). HMGA2-/+ gilts and boars exhibited normal reproductive development and fertility, while HMGA2-/- boars were sterile due to undescended testes (cryptorchidism). Crossbreeding HMGA2-/+ boars and gilts produced litters lacking the HMGA2-/- genotype. However, analysis of day (D) D40 and D78 pregnancies indicated that HMGA2-/- fetuses were present at the expected Mendelian ratio, but placental abnormalities were seen in the D78 HMGA2-/- concepti. Additionally, HMGA2-/- embryos generated by gene editing and SCNT produced multiple pregnancies and viable offspring, indicating that lack of HMGA2 is not lethal per se. Overall, our results show that the effect of HMGA2 with respect to growth regulation is highly conserved among mammals and opens up the possibility of regulating body and organ size in a variety of mammalian species including food and companion animals.}, } @article {pmid29735701, year = {2018}, author = {Lembke-Jene, L and Tiedemann, R and Nürnberg, D and Gong, X and Lohmann, G}, title = {Rapid shift and millennial-scale variations in Holocene North Pacific Intermediate Water ventilation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5365-5370}, pmid = {29735701}, issn = {1091-6490}, abstract = {The Pacific hosts the largest oxygen minimum zones (OMZs) in the world ocean, which are thought to intensify and expand under future climate change, with significant consequences for marine ecosystems, biogeochemical cycles, and fisheries. At present, no deep ventilation occurs in the North Pacific due to a persistent halocline, but relatively better-oxygenated subsurface North Pacific Intermediate Water (NPIW) mitigates OMZ development in lower latitudes. Over the past decades, instrumental data show decreasing oxygenation in NPIW; however, long-term variations in middepth ventilation are potentially large, obscuring anthropogenic influences against millennial-scale natural background shifts. Here, we use paleoceanographic proxy evidence from the Okhotsk Sea, the foremost North Pacific ventilation region, to show that its modern oxygenated pattern is a relatively recent feature, with little to no ventilation before six thousand years ago, constituting an apparent Early-Middle Holocene (EMH) threshold or "tipping point." Complementary paleomodeling results likewise indicate a warmer, saltier EMH NPIW, different from its modern conditions. During the EMH, the Okhotsk Sea switched from a modern oxygenation source to a sink, through a combination of sea ice loss, higher water temperatures, and remineralization rates, inhibiting ventilation. We estimate a strongly decreased EMH NPIW oxygenation of ∼30 to 50%, and increased middepth Pacific nutrient concentrations and carbon storage. Our results (i) imply that under past or future warmer-than-present conditions, oceanic biogeochemical feedback mechanisms may change or even switch direction, and (ii) provide constraints on the high-latitude North Pacific's influence on mesopelagic ventilation dynamics, with consequences for large oceanic regions.}, } @article {pmid29735700, year = {2018}, author = {Davis, RJ and Gönen, M and Margineantu, DH and Handeli, S and Swanger, J and Hoellerbauer, P and Paddison, PJ and Gu, H and Raftery, D and Grim, JE and Hockenbery, DM and Margolin, AA and Clurman, BE}, title = {Pan-cancer transcriptional signatures predictive of oncogenic mutations reveal that Fbw7 regulates cancer cell oxidative metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5462-5467}, doi = {10.1073/pnas.1718338115}, pmid = {29735700}, issn = {1091-6490}, support = {R01 CA190957/CA/NCI NIH HHS/United States ; R01 CA193808/CA/NCI NIH HHS/United States ; P30 CA015704/CA/NCI NIH HHS/United States ; U54 CA209988/CA/NCI NIH HHS/United States ; U01 CA217862/CA/NCI NIH HHS/United States ; }, mesh = {Cell Respiration ; Colorectal Neoplasms/genetics/*metabolism/*pathology ; F-Box-WD Repeat-Containing Protein 7/*genetics/*metabolism ; Gene Expression Profiling ; Humans ; *Metabolome ; Mitochondria/*metabolism/pathology ; *Mutation ; Oxidative Phosphorylation ; Oxidative Stress ; Phosphorylation ; Ubiquitin ; Ubiquitination ; }, abstract = {The Fbw7 (F-box/WD repeat-containing protein 7) ubiquitin ligase targets multiple oncoproteins for degradation and is commonly mutated in cancers. Like other pleiotropic tumor suppressors, Fbw7's complex biology has impeded our understanding of how Fbw7 mutations promote tumorigenesis and hindered the development of targeted therapies. To address these needs, we employed a transfer learning approach to derive gene-expression signatures from The Cancer Gene Atlas datasets that predict Fbw7 mutational status across tumor types and identified the pathways enriched within these signatures. Genes involved in mitochondrial function were highly enriched in pan-cancer signatures that predict Fbw7 mutations. Studies in isogenic colorectal cancer cell lines that differed in Fbw7 mutational status confirmed that Fbw7 mutations increase mitochondrial gene expression. Surprisingly, Fbw7 mutations shifted cellular metabolism toward oxidative phosphorylation and caused context-specific metabolic vulnerabilities. Our approach revealed unexpected metabolic reprogramming and possible therapeutic targets in Fbw7-mutant cancers and provides a framework to study other complex, oncogenic mutations.}, } @article {pmid29735699, year = {2018}, author = {Dasgupta, S and Gupta, K and Zhang, Y and Viasnoff, V and Prost, J}, title = {Physics of lumen growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4751-E4757}, pmid = {29735699}, issn = {1091-6490}, mesh = {Animals ; Cells, Cultured ; Hepatocytes/*cytology/*physiology ; Intercellular Junctions/*chemistry/*physiology ; *Models, Theoretical ; *Osmosis ; Rats ; }, abstract = {We model the dynamics of formation of intercellular secretory lumens. Using conservation laws, we quantitatively study the balance between paracellular leaks and the build-up of osmotic pressure in the lumen. Our model predicts a critical pumping threshold to expand stable lumens. Consistently with experimental observations in bile canaliculi, the model also describes a transition between a monotonous and oscillatory regime during luminogenesis as a function of ion and water transport parameters. We finally discuss the possible importance of regulation of paracellular leaks in intercellular tubulogenesis.}, } @article {pmid29735698, year = {2018}, author = {Zheng, L and Dong, H and Wu, X and Huang, YL and Wang, W and Wu, W and Wang, Z and Lai, K}, title = {Interferometric imaging of nonlocal electromechanical power transduction in ferroelectric domains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5338-5342}, pmid = {29735698}, issn = {1091-6490}, abstract = {The electrical generation and detection of elastic waves are the foundation for acoustoelectronic and acoustooptic systems. For surface acoustic wave devices, microelectromechanical/nanoelectromechanical systems, and phononic crystals, tailoring the spatial variation of material properties such as piezoelectric and elastic tensors may bring significant improvements to the system performance. Due to the much slower speed of sound than speed of light in solids, it is desirable to study various electroacoustic behaviors at the mesoscopic length scale. In this work, we demonstrate the interferometric imaging of electromechanical power transduction in ferroelectric lithium niobate domain structures by microwave impedance microscopy. In sharp contrast to the traditional standing-wave patterns caused by the superposition of counterpropagating waves, the constructive and destructive fringes in microwave dissipation images exhibit an intriguing one-wavelength periodicity. We show that such unusual interference patterns, which are fundamentally different from the acoustic displacement fields, stem from the nonlocal interaction between electric fields and elastic waves. The results are corroborated by numerical simulations taking into account the sign reversal of piezoelectric tensor in oppositely polarized domains. Our work paves ways to probe nanoscale electroacoustic phenomena in complex structures by near-field electromagnetic imaging.}, } @article {pmid29735697, year = {2018}, author = {Liu, Z and Sun, J and Mao, J and Zhu, H and Ren, W and Zhou, J and Wang, Z and Singh, DJ and Sui, J and Chu, CW and Ren, Z}, title = {Phase-transition temperature suppression to achieve cubic GeTe and high thermoelectric performance by Bi and Mn codoping.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5332-5337}, pmid = {29735697}, issn = {1091-6490}, abstract = {Germanium telluride (GeTe)-based materials, which display intriguing functionalities, have been intensively studied from both fundamental and technological perspectives. As a thermoelectric material, though, the phase transition in GeTe from a rhombohedral structure to a cubic structure at ∼700 K is a major obstacle impeding applications for energy harvesting. In this work, we discovered that the phase-transition temperature can be suppressed to below 300 K by a simple Bi and Mn codoping, resulting in the high performance of cubic GeTe from 300 to 773 K. Bi doping on the Ge site was found to reduce the hole concentration and thus to enhance the thermoelectric properties. Mn alloying on the Ge site simultaneously increased the hole effective mass and the Seebeck coefficient through modification of the valence bands. With the Bi and Mn codoping, the lattice thermal conductivity was also largely reduced due to the strong point-defect scattering for phonons, resulting in a peak thermoelectric figure of merit (ZT) of ∼1.5 at 773 K and an average ZT of ∼1.1 from 300 to 773 K in cubic Ge0.81Mn0.15Bi0.04Te. Our results open the door for further studies of this exciting material for thermoelectric and other applications.}, } @article {pmid29735696, year = {2018}, author = {Bertelsmeier, C and Ollier, S and Liebhold, AM and Brockerhoff, EG and Ward, D and Keller, L}, title = {Recurrent bridgehead effects accelerate global alien ant spread.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5486-5491}, pmid = {29735696}, issn = {1091-6490}, mesh = {Animals ; Ants/*physiology ; *Biodiversity ; *Ecosystem ; *Introduced Species ; New Zealand ; United States ; }, abstract = {Biological invasions are a major threat to biological diversity, agriculture, and human health. To predict and prevent new invasions, it is crucial to develop a better understanding of the drivers of the invasion process. The analysis of 4,533 border interception events revealed that at least 51 different alien ant species were intercepted at US ports over a period of 70 years (1914-1984), and 45 alien species were intercepted entering New Zealand over a period of 68 years (1955-2013). Most of the interceptions did not originate from species' native ranges but instead came from invaded areas. In the United States, 75.7% of the interceptions came from a country where the intercepted ant species had been previously introduced. In New Zealand, this value was even higher, at 87.8%. There was an overrepresentation of interceptions from nearby locations (Latin America for species intercepted in the United States and Oceania for species intercepted in New Zealand). The probability of a species' successful establishment in both the United States and New Zealand was positively related to the number of interceptions of the species in these countries. Moreover, species that have spread to more continents are also more likely to be intercepted and to make secondary introductions. This creates a positive feedback loop between the introduction and establishment stages of the invasion process, in which initial establishments promote secondary introductions. Overall, these results reveal that secondary introductions act as a critical driver of increasing global rates of invasions.}, } @article {pmid29735695, year = {2018}, author = {Pakharukova, N and Tuittila, M and Paavilainen, S and Malmi, H and Parilova, O and Teneberg, S and Knight, SD and Zavialov, AV}, title = {Structural basis for Acinetobacter baumannii biofilm formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5558-5563}, doi = {10.1073/pnas.1800961115}, pmid = {29735695}, issn = {1091-6490}, mesh = {Acinetobacter baumannii/*chemistry/metabolism ; Adhesins, Bacterial/*chemistry/metabolism ; Amino Acid Sequence ; Bacterial Adhesion/*physiology ; Bacterial Proteins/*chemistry/metabolism ; Biofilms/*growth & development ; Crystallography, X-Ray ; Fimbriae, Bacterial/*chemistry/metabolism ; Molecular Chaperones/*chemistry/metabolism ; Phylogeny ; Sequence Homology ; }, abstract = {Acinetobacter baumannii-a leading cause of nosocomial infections-has a remarkable capacity to persist in hospital environments and medical devices due to its ability to form biofilms. Biofilm formation is mediated by Csu pili, assembled via the "archaic" chaperone-usher pathway. The X-ray structure of the CsuC-CsuE chaperone-adhesin preassembly complex reveals the basis for bacterial attachment to abiotic surfaces. CsuE exposes three hydrophobic finger-like loops at the tip of the pilus. Decreasing the hydrophobicity of these abolishes bacterial attachment, suggesting that archaic pili use tip-fingers to detect and bind to hydrophobic cavities in substrates. Antitip antibody completely blocks biofilm formation, presenting a means to prevent the spread of the pathogen. The use of hydrophilic materials instead of hydrophobic plastics in medical devices may represent another simple and cheap solution to reduce pathogen spread. Phylogenetic analysis suggests that the tip-fingers binding mechanism is shared by all archaic pili carrying two-domain adhesins. The use of flexible fingers instead of classical receptor-binding cavities is presumably more advantageous for attachment to structurally variable substrates, such as abiotic surfaces.}, } @article {pmid29735694, year = {2018}, author = {Zhao, J and Lupino, K and Wilkins, BJ and Qiu, C and Liu, J and Omura, Y and Allred, AL and McDonald, C and Susztak, K and Barish, GD and Pei, L}, title = {Genomic integration of ERRγ-HNF1β regulates renal bioenergetics and prevents chronic kidney disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4910-E4919}, pmid = {29735694}, issn = {1091-6490}, support = {R01 DK111495/DK/NIDDK NIH HHS/United States ; DP3 DK108220/DK/NIDDK NIH HHS/United States ; R01 DK087635/DK/NIDDK NIH HHS/United States ; R01 DK108987/DK/NIDDK NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; K08 DK099379/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cysts/metabolism/pathology/*prevention & control ; *Energy Metabolism ; *Epigenomics ; *Gene Expression Regulation ; Hepatocyte Nuclear Factor 1-beta/*genetics/metabolism/physiology ; Humans ; Kidney/metabolism/pathology ; Mice ; Mice, Knockout ; Mitochondria/metabolism/pathology ; Promoter Regions, Genetic ; Receptors, Estrogen/*genetics/metabolism/physiology ; Renal Insufficiency, Chronic/metabolism/pathology/*prevention & control ; }, abstract = {Mitochondrial dysfunction is increasingly recognized as a critical determinant of both hereditary and acquired kidney diseases. However, it remains poorly understood how mitochondrial metabolism is regulated to support normal kidney function and how its dysregulation contributes to kidney disease. Here, we show that the nuclear receptor estrogen-related receptor gamma (ERRγ) and hepatocyte nuclear factor 1 beta (HNF1β) link renal mitochondrial and reabsorptive functions through coordinated epigenomic programs. ERRγ directly regulates mitochondrial metabolism but cooperatively controls renal reabsorption via convergent binding with HNF1β. Deletion of ERRγ in renal epithelial cells (RECs), in which it is highly and specifically expressed, results in severe renal energetic and reabsorptive dysfunction and progressive renal failure that recapitulates phenotypes of animals and patients with HNF1β loss-of-function gene mutations. Moreover, ERRγ expression positively correlates with renal function and is decreased in patients with chronic kidney disease (CKD). REC-ERRγ KO mice share highly overlapping renal transcriptional signatures with human patients with CKD. Together these findings reveal a role for ERRγ in directing independent and HNF1β-integrated programs for energy production and use essential for normal renal function and the prevention of kidney disease.}, } @article {pmid29735693, year = {2018}, author = {Cheng, YC and Shieh, SY}, title = {Deubiquitinating enzyme USP3 controls CHK1 chromatin association and activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5546-5551}, doi = {10.1073/pnas.1719856115}, pmid = {29735693}, issn = {1091-6490}, mesh = {Checkpoint Kinase 1/genetics/*metabolism ; Chromatin/genetics/*metabolism ; DNA Damage ; Enzyme Activation ; *Genomic Instability ; HeLa Cells ; Histones/genetics/*metabolism ; Humans ; Phosphorylation ; Protein Processing, Post-Translational ; Signal Transduction ; Ubiquitin/*metabolism ; Ubiquitin-Specific Proteases/genetics/*metabolism ; Ubiquitination ; }, abstract = {Checkpoint kinase 1 (CHK1), a Ser/Thr protein kinase, is modified by the K63-linked ubiquitin chain in response to genotoxic stress, which promotes its nuclear localization, chromatin association, and activation. Interestingly, this bulky modification is linked to a critical residue, K132, at the kinase active site. It is unclear how this modification affects the kinase activity and how it is removed to enable the release of CHK1 from chromatin. Herein, we show that the K63-linked ubiquitin chain at CHK1's K132 residue has an inhibitory effect on the kinase activity. Furthermore, we demonstrate that this modification can be removed by ubiquitin-specific protease 3 (USP3), a deubiquitinating enzyme that targets K63-linked ubiquitin chains. Wild-type USP3, but not the catalytically defective or nuclear localization sequence-deficient mutants, reduced CHK1 K63-linked ubiquitination. Conversely, USP3 knockdown elevated K63-linked ubiquitination of the kinase, leading to prolonged CHK1 chromatin association and phosphorylation. Paradoxically, by removing the bulky ubiquitin chain at the active site, USP3 also increased the accessibility of CHK1 to its substrates. Thus, our findings on the dual roles of USP3 (namely, one to release CHK1 from the chromatin and the other to open up the active site) provide further insights into the regulation of CHK1 following DNA damage.}, } @article {pmid29735692, year = {2018}, author = {Kannan, A and Yang, Z and Kim, MK and Stone, HA and Siryaporn, A}, title = {Dynamic switching enables efficient bacterial colonization in flow.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5438-5443}, pmid = {29735692}, issn = {1091-6490}, support = {K22 AI112816/AI/NIAID NIH HHS/United States ; }, mesh = {*Bacterial Physiological Phenomena ; Biofilms/*growth & development ; Hydrodynamics ; Pseudomonas aeruginosa/*growth & development/physiology ; Water Movements ; }, abstract = {Bacteria colonize environments that contain networks of moving fluids, including digestive pathways, blood vasculature in animals, and the xylem and phloem networks in plants. In these flow networks, bacteria form distinct biofilm structures that have an important role in pathogenesis. The physical mechanisms that determine the spatial organization of bacteria in flow are not understood. Here, we show that the bacterium P. aeruginosa colonizes flow networks using a cyclical process that consists of surface attachment, upstream movement, detachment, movement with the bulk flow, and surface reattachment. This process, which we have termed dynamic switching, distributes bacterial subpopulations upstream and downstream in flow through two phases: movement on surfaces and cellular movement via the bulk. The model equations that describe dynamic switching are identical to those that describe dynamic instability, a process that enables microtubules in eukaryotic cells to search space efficiently to capture chromosomes. Our results show that dynamic switching enables bacteria to explore flow networks efficiently, which maximizes dispersal and colonization and establishes the organizational structure of biofilms. A number of eukaryotic and mammalian cells also exhibit movement in two phases in flow, which suggests that dynamic switching is a modality that enables efficient dispersal for a broad range of cell types.}, } @article {pmid29735691, year = {2018}, author = {Konstantinou, K and Lee, TH and Mocanu, FC and Elliott, SR}, title = {Origin of radiation tolerance in amorphous Ge2Sb2Te5 phase-change random-access memory material.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5353-5358}, pmid = {29735691}, issn = {1091-6490}, abstract = {The radiation hardness of amorphous Ge2Sb2Te5 phase-change random-access memory material has been elucidated by ab initio molecular-dynamics simulations. Ionizing radiation events have been modeled to investigate their effect on the atomic and electronic structure of the glass. Investigation of the short- and medium-range order highlights a structural recovery of the amorphous network after exposure to the high-energy events modeled in this study. Analysis of the modeled glasses reveals specific structural rearrangements in the local atomic geometry of the glass, as well as an increase in the formation of large shortest-path rings. The electronic structure of the modeled system is not significantly affected by the ionizing radiation events, since negligible differences have been observed before and after irradiation. These results provide a detailed insight into the atomistic structure of amorphous Ge2Sb2Te5 after irradiation and demonstrate the radiation hardness of the glass matrix.}, } @article {pmid29735690, year = {2018}, author = {Gómez-Romero, L and Palacios-Flores, K and Reyes, J and García, D and Boege, M and Dávila, G and Flores, M and Schatz, MC and Palacios, R}, title = {Precise detection of de novo single nucleotide variants in human genomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5516-5521}, pmid = {29735690}, issn = {1091-6490}, support = {R01 HG006677/HG/NHGRI NIH HHS/United States ; }, mesh = {Algorithms ; Child ; *DNA Copy Number Variations ; *Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Parents ; *Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/*methods ; *Software ; }, abstract = {The precise determination of de novo genetic variants has enormous implications across different fields of biology and medicine, particularly personalized medicine. Currently, de novo variations are identified by mapping sample reads from a parent-offspring trio to a reference genome, allowing for a certain degree of differences. While widely used, this approach often introduces false-positive (FP) results due to misaligned reads and mischaracterized sequencing errors. In a previous study, we developed an alternative approach to accurately identify single nucleotide variants (SNVs) using only perfect matches. However, this approach could be applied only to haploid regions of the genome and was computationally intensive. In this study, we present a unique approach, coverage-based single nucleotide variant identification (COBASI), which allows the exploration of the entire genome using second-generation short sequence reads without extensive computing requirements. COBASI identifies SNVs using changes in coverage of exactly matching unique substrings, and is particularly suited for pinpointing de novo SNVs. Unlike other approaches that require population frequencies across hundreds of samples to filter out any methodological biases, COBASI can be applied to detect de novo SNVs within isolated families. We demonstrate this capability through extensive simulation studies and by studying a parent-offspring trio we sequenced using short reads. Experimental validation of all 58 candidate de novo SNVs and a selection of non-de novo SNVs found in the trio confirmed zero FP calls. COBASI is available as open source at https://github.com/Laura-Gomez/COBASI for any researcher to use.}, } @article {pmid29735689, year = {2018}, author = {Lee, Y and Howe, C and Mishra, S and Lee, DS and Mahmood, M and Piper, M and Kim, Y and Tieu, K and Byun, HS and Coffey, JP and Shayan, M and Chun, Y and Costanzo, RM and Yeo, WH}, title = {Wireless, intraoral hybrid electronics for real-time quantification of sodium intake toward hypertension management.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5377-5382}, pmid = {29735689}, issn = {1091-6490}, mesh = {Adult ; *Dental Prosthesis ; Electronics/*instrumentation ; Equipment Design ; Humans ; Hypertension/*prevention & control ; Male ; Sodium/*analysis ; Wearable Electronic Devices/*statistics & numerical data ; Wireless Technology/*instrumentation ; }, abstract = {Recent wearable devices offer portable monitoring of biopotentials, heart rate, or physical activity, allowing for active management of human health and wellness. Such systems can be inserted in the oral cavity for measuring food intake in regard to controlling eating behavior, directly related to diseases such as hypertension, diabetes, and obesity. However, existing devices using plastic circuit boards and rigid sensors are not ideal for oral insertion. A user-comfortable system for the oral cavity requires an ultrathin, low-profile, and soft electronic platform along with miniaturized sensors. Here, we introduce a stretchable hybrid electronic system that has an exceptionally small form factor, enabling a long-range wireless monitoring of sodium intake. Computational study of flexible mechanics and soft materials provides fundamental aspects of key design factors for a tissue-friendly configuration, incorporating a stretchable circuit and sensor. Analytical calculation and experimental study enables reliable wireless circuitry that accommodates dynamic mechanical stress. Systematic in vitro modeling characterizes the functionality of a sodium sensor in the electronics. In vivo demonstration with human subjects captures the device feasibility for real-time quantification of sodium intake, which can be used to manage hypertension.}, } @article {pmid29735688, year = {2018}, author = {Yang, Y and Adebali, O and Wu, G and Selby, CP and Chiou, YY and Rashid, N and Hu, J and Hogenesch, JB and Sancar, A}, title = {Cisplatin-DNA adduct repair of transcribed genes is controlled by two circadian programs in mouse tissues.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4777-E4785}, doi = {10.1073/pnas.1804493115}, pmid = {29735688}, issn = {1091-6490}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R35 GM118102/GM/NIGMS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 NS054794/NS/NINDS NIH HHS/United States ; R01 ES027255/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Circadian Rhythm/drug effects/*genetics ; Cisplatin/*pharmacology ; DNA Adducts/*pharmacology ; *DNA Damage ; *DNA Repair ; Female ; *Genome, Human ; Humans ; Mice ; Mice, Inbred C57BL ; Neoplasms/drug therapy/*genetics ; Transcription, Genetic/drug effects ; }, abstract = {Cisplatin is a major cancer chemotherapeutic drug. It kills cancer cells by damaging their DNA, mainly in the form of Pt-d(GpG) diadducts. However, it also has serious side effects, including nephrotoxicity and hepatotoxicity that limit its usefulness. Chronotherapy is taking circadian time into account during therapy to improve the therapeutic index, by improving efficacy and/or limiting toxicity. To this end, we tested the impact of clock time on excision repair of cisplatin-induced DNA damage at single-nucleotide resolution across the genome in mouse kidney and liver. We found that genome repair is controlled by two circadian programs. Repair of the transcribed strand (TS) of active, circadian-controlled genes is dictated by each gene's phase of transcription, which falls across the circadian cycle with prominent peaks at dawn and dusk. In contrast, repair of the nontranscribed strand (NTS) of all genes, repair of intergenic DNA, and global repair overall peaks at Zeitgeber time ZT08, as basal repair capacity, which is controlled by the circadian clock, peaks at this circadian time. Consequently, the TS and NTS of many genes are repaired out of phase. As most cancers are thought to have defective circadian rhythms, these results suggest that future research on timed dosage of cisplatin could potentially reduce damage to healthy tissue and improve its therapeutic index.}, } @article {pmid29735687, year = {2018}, author = {Robustelli, P and Piana, S and Shaw, DE}, title = {Developing a molecular dynamics force field for both folded and disordered protein states.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4758-E4766}, pmid = {29735687}, issn = {1091-6490}, mesh = {Humans ; Intrinsically Disordered Proteins/*chemistry ; *Models, Theoretical ; *Molecular Dynamics Simulation ; *Protein Folding ; Protein Structure, Secondary ; }, abstract = {Molecular dynamics (MD) simulation is a valuable tool for characterizing the structural dynamics of folded proteins and should be similarly applicable to disordered proteins and proteins with both folded and disordered regions. It has been unclear, however, whether any physical model (force field) used in MD simulations accurately describes both folded and disordered proteins. Here, we select a benchmark set of 21 systems, including folded and disordered proteins, simulate these systems with six state-of-the-art force fields, and compare the results to over 9,000 available experimental data points. We find that none of the tested force fields simultaneously provided accurate descriptions of folded proteins, of the dimensions of disordered proteins, and of the secondary structure propensities of disordered proteins. Guided by simulation results on a subset of our benchmark, however, we modified parameters of one force field, achieving excellent agreement with experiment for disordered proteins, while maintaining state-of-the-art accuracy for folded proteins. The resulting force field, a99SB-disp, should thus greatly expand the range of biological systems amenable to MD simulation. A similar approach could be taken to improve other force fields.}, } @article {pmid29735686, year = {2018}, author = {Fazio, L and Pergola, G and Papalino, M and Di Carlo, P and Monda, A and Gelao, B and Amoroso, N and Tangaro, S and Rampino, A and Popolizio, T and Bertolino, A and Blasi, G}, title = {Transcriptomic context of DRD1 is associated with prefrontal activity and behavior during working memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5582-5587}, pmid = {29735686}, issn = {1091-6490}, support = {R37 MH057881/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; P50 MH084053/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; P01 AG002219/AG/NIA NIH HHS/United States ; R01 MH093725/MH/NIMH NIH HHS/United States ; P50 AG005138/AG/NIA NIH HHS/United States ; HHSN271201300031C/MH/NIMH NIH HHS/United States ; P50 MH066392/MH/NIMH NIH HHS/United States ; R01 MH080405/MH/NIMH NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Female ; Healthy Volunteers ; Humans ; Magnetic Resonance Imaging ; Male ; Memory/*physiology ; Middle Aged ; *Neuropsychological Tests ; *Polymorphism, Single Nucleotide ; Prefrontal Cortex/*physiology ; Receptors, Dopamine D1/*genetics/*metabolism ; *Transcriptome ; }, abstract = {Dopamine D1 receptor (D1R) signaling shapes prefrontal cortex (PFC) activity during working memory (WM). Previous reports found higher WM performance associated with alleles linked to greater expression of the gene coding for D1Rs (DRD1). However, there is no evidence on the relationship between genetic modulation of DRD1 expression in PFC and patterns of prefrontal activity during WM. Furthermore, previous studies have not considered that D1Rs are part of a coregulated molecular environment, which may contribute to D1R-related prefrontal WM processing. Thus, we hypothesized a reciprocal link between a coregulated (i.e., coexpressed) molecular network including DRD1 and PFC activity. To explore this relationship, we used three independent postmortem prefrontal mRNA datasets (total n = 404) to characterize a coexpression network including DRD1 Then, we indexed network coexpression using a measure (polygenic coexpression index-DRD1-PCI) combining the effect of single nucleotide polymorphisms (SNPs) on coexpression. Finally, we associated the DRD1-PCI with WM performance and related brain activity in independent samples of healthy participants (total n = 371). We identified and replicated a coexpression network including DRD1, whose coexpression was correlated with DRD1-PCI. We also found that DRD1-PCI was associated with lower PFC activity and higher WM performance. Behavioral and imaging results were replicated in independent samples. These findings suggest that genetically predicted expression of DRD1 and of its coexpression partners stratifies healthy individuals in terms of WM performance and related prefrontal activity. They also highlight genes and SNPs potentially relevant to pharmacological trials aimed to test cognitive enhancers modulating DRD1 signaling.}, } @article {pmid29735685, year = {2018}, author = {Brynildsrud, OB and Eldholm, V and Bohlin, J and Uadiale, K and Obaro, S and Caugant, DA}, title = {Acquisition of virulence genes by a carrier strain gave rise to the ongoing epidemics of meningococcal disease in West Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5510-5515}, pmid = {29735685}, issn = {1091-6490}, mesh = {Africa, Western/epidemiology ; Antigens, Bacterial/genetics/immunology ; *Epidemics ; Gene Expression Profiling ; Humans ; Meningitis, Meningococcal/*epidemiology/microbiology/prevention & control ; Meningococcal Vaccines/*administration & dosage/immunology ; Neisseria meningitidis/classification/genetics/immunology/*isolation & purification ; Population Surveillance ; Spatio-Temporal Analysis ; Viral Proteins/*genetics ; Virulence/*genetics ; }, abstract = {In the African meningitis belt, a region of sub-Saharan Africa comprising 22 countries from Senegal in the west to Ethiopia in the east, large epidemics of serogroup A meningococcal meningitis have occurred periodically. After gradual introduction from 2010 of mass vaccination with a monovalent meningococcal A conjugate vaccine, serogroup A epidemics have been eliminated. Starting in 2013, the northwestern part of Nigeria has been affected by yearly outbreaks of meningitis caused by a novel strain of serogroup C Neisseria meningitidis (NmC). In 2015, the strain spread to the neighboring country Niger, where it caused a severe epidemic. Following a relative calm in 2016, the largest ever recorded epidemic of NmC broke out in Nigeria in 2017. Here, we describe the recent evolution of this new outbreak strain and show how the acquisition of capsule genes and virulence factors by a strain previously circulating asymptomatically in the African population led to the emergence of a virulent pathogen. This study illustrates the power of long-read whole-genome sequencing, combined with Illumina sequencing, for high-resolution epidemiological investigations.}, } @article {pmid29735684, year = {2018}, author = {Kent, DV and Olsen, PE and Rasmussen, C and Lepre, C and Mundil, R and Irmis, RB and Gehrels, GE and Giesler, D and Geissman, JW and Parker, WG}, title = {Empirical evidence for stability of the 405-kiloyear Jupiter-Venus eccentricity cycle over hundreds of millions of years.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6153-6158}, doi = {10.1073/pnas.1800891115}, pmid = {29735684}, issn = {1091-6490}, abstract = {The Newark-Hartford astrochronostratigraphic polarity timescale (APTS) was developed using a theoretically constant 405-kiloyear eccentricity cycle linked to gravitational interactions with Jupiter-Venus as a tuning target and provides a major timing calibration for about 30 million years of Late Triassic and earliest Jurassic time. While the 405-ky cycle is both unimodal and the most metronomic of the major orbital cycles thought to pace Earth's climate in numerical solutions, there has been little empirical confirmation of that behavior, especially back before the limits of orbital solutions at about 50 million years before present. Moreover, the APTS is anchored only at its younger end by U-Pb zircon dates at 201.6 million years before present and could even be missing a number of 405-ky cycles. To test the validity of the dangling APTS and orbital periodicities, we recovered a diagnostic magnetic polarity sequence in the volcaniclastic-bearing Chinle Formation in a scientific drill core from Petrified Forest National Park (Arizona) that provides an unambiguous correlation to the APTS. New high precision U-Pb detrital zircon dates from the core are indistinguishable from ages predicted by the APTS back to 215 million years before present. The agreement shows that the APTS is continuous and supports a stable 405-kiloyear cycle well beyond theoretical solutions. The validated Newark-Hartford APTS can be used as a robust framework to help differentiate provinciality from global temporal patterns in the ecological rise of early dinosaurs in the Late Triassic, amongst other problems.}, } @article {pmid29735683, year = {2018}, author = {Filip, MR and Giustino, F}, title = {The geometric blueprint of perovskites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5397-5402}, pmid = {29735683}, issn = {1091-6490}, abstract = {Perovskite minerals form an essential component of the Earth's mantle, and synthetic crystals are ubiquitous in electronics, photonics, and energy technology. The extraordinary chemical diversity of these crystals raises the question of how many and which perovskites are yet to be discovered. Here we show that the "no-rattling" principle postulated by Goldschmidt in 1926, describing the geometric conditions under which a perovskite can form, is much more effective than previously thought and allows us to predict perovskites with a fidelity of 80%. By supplementing this principle with inferential statistics and internet data mining we establish that currently known perovskites are only the tip of the iceberg, and we enumerate 90,000 hitherto-unknown compounds awaiting to be studied. Our results suggest that geometric blueprints may enable the systematic screening of millions of compounds and offer untapped opportunities in structure prediction and materials design.}, } @article {pmid29735682, year = {2018}, author = {Terasaka, N and Azuma, Y and Hilvert, D}, title = {Laboratory evolution of virus-like nucleocapsids from nonviral protein cages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5432-5437}, doi = {10.1073/pnas.1800527115}, pmid = {29735682}, issn = {1091-6490}, mesh = {Bacteria/*enzymology/genetics ; *Bioengineering ; Capsid Proteins/chemistry/genetics/*metabolism ; *Directed Molecular Evolution ; Models, Molecular ; Multienzyme Complexes/chemistry/genetics/*metabolism ; Nucleocapsid/chemistry/genetics/*metabolism ; Peptide Fragments/*metabolism ; Virus Assembly ; }, abstract = {Viruses are remarkable nanomachines that efficiently hijack cellular functions to replicate and self-assemble their components within a complex biological environment. As all steps of the viral life cycle depend on formation of a protective proteinaceous shell that packages the DNA or RNA genome, bottom-up construction of virus-like nucleocapsids from nonviral materials could provide valuable insights into virion assembly and evolution. Such constructs could also serve as safe alternatives to natural viruses for diverse nano- and biotechnological applications. Here we show that artificial virus-like nucleocapsids can be generated-rapidly and surprisingly easily-by engineering and laboratory evolution of a nonviral protein cage formed by Aquifex aeolicus lumazine synthase (AaLS) and its encoding mRNA. Cationic peptides were appended to the engineered capsid proteins to enable specific recognition of packaging signals on cognate mRNAs, and subsequent evolutionary optimization afforded nucleocapsids with expanded spherical structures that encapsulate their own full-length RNA genome in vivo and protect the cargo molecules from nucleases. These findings provide strong experimental support for the hypothesis that subcellular protein-bounded compartments may have facilitated the emergence of ancient viruses.}, } @article {pmid29735681, year = {2018}, author = {Kobayashi, A and Horikawa, M and Kirschvink, JL and Golash, HN}, title = {Magnetic control of heterogeneous ice nucleation with nanophase magnetite: Biophysical and agricultural implications.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5383-5388}, pmid = {29735681}, issn = {1091-6490}, mesh = {Agriculture ; Animals ; Apium/*chemistry ; *Biophysics ; Cattle ; Crystallization ; *Ferrosoferric Oxide ; *Freezing ; *Ice ; Muscles/*chemistry ; Nanoparticles/chemistry ; Physical Phenomena ; Water/*chemistry ; }, abstract = {In supercooled water, ice nucleation is a stochastic process that requires ∼250-300 molecules to transiently achieve structural ordering before an embryonic seed crystal can nucleate. This happens most easily on crystalline surfaces, in a process termed heterogeneous nucleation; without such surfaces, water droplets will supercool to below -30 °C before eventually freezing homogeneously. A variety of fundamental processes depends on heterogeneous ice nucleation, ranging from desert-blown dust inducing precipitation in clouds to frost resistance in plants. Recent experiments have shown that crystals of nanophase magnetite (Fe3O4) are powerful nucleation sites for this heterogeneous crystallization of ice, comparable to other materials like silver iodide and some cryobacterial peptides. In natural materials containing magnetite, its ferromagnetism offers the possibility that magneto-mechanical motion induced by external oscillating magnetic fields could act to disrupt the water-crystal interface, inhibiting the heterogeneous nucleation process in subfreezing water and promoting supercooling. For this to act, the magneto-mechanical rotation of the particles should be higher than the magnitude of Brownian motions. We report here that 10-Hz precessing magnetic fields, at strengths of 1 mT and above, on ∼50-nm magnetite crystals dispersed in ultrapure water, meet these criteria and do indeed produce highly significant supercooling. Using these rotating magnetic fields, we were able to elicit supercooling in two representative plant and animal tissues (celery and bovine muscle), both of which have detectable, natural levels of ferromagnetic material. Tailoring magnetic oscillations for the magnetite particle size distribution in different tissues could maximize this supercooling effect.}, } @article {pmid29735680, year = {2018}, author = {Song, Q and Ando, A and Xu, D and Fang, L and Zhang, T and Huq, E and Qiao, H and Deng, XW and Chen, ZJ}, title = {Diurnal down-regulation of ethylene biosynthesis mediates biomass heterosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5606-5611}, doi = {10.1073/pnas.1722068115}, pmid = {29735680}, issn = {1091-6490}, support = {R01 GM109076/GM/NIGMS NIH HHS/United States ; R01 GM114297/GM/NIGMS NIH HHS/United States ; R01 GM115879/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; *Biomass ; *Circadian Rhythm ; Ethylenes/*biosynthesis ; *Gene Expression Regulation, Plant ; Hybrid Vigor/*physiology ; }, abstract = {Heterosis is widely applied in agriculture; however, the underlying molecular mechanisms for superior performance are not well understood. Ethylene biosynthesis and signaling genes are shown to be down-regulated in Arabidopsis interspecific hybrids. Ethylene is a plant hormone that promotes fruit ripening and maturation but inhibits hypocotyl elongation. Here we report that application of exogenous ethylene could eliminate biomass vigor in Arabidopsis thaliana F1 hybrids, suggesting a negative role of ethylene in heterosis. Ethylene biosynthesis is mediated by the rate-limiting enzyme, 1-aminocyclopropane-1-carboxylate synthase (ACS). Down-regulation of ACS genes led to the decrease of ethylene production, which was associated with the high-vigor F1 hybrids, but not with the low-vigor ones. At the mechanistic level, expression of ACS genes was down-regulated diurnally and indirectly by Circadian Clock Associated 1 (CCA1) during the day and directly by Phyotochrome-Interacting Factor 5 (PIF5) at night. Consistent with the negative role of ethylene in plant growth, biomass vigor was higher in the acs mutants than in wild-type plants, while increasing endogenous ethylene production in the hybridizing parents reduced growth vigor in the hybrids. Thus, integrating circadian rhythms and light signaling into ethylene production is another regulatory module of complex biological networks, leading to biomass heterosis in plants.}, } @article {pmid29735679, year = {2018}, author = {Thutupalli, S and Geyer, D and Singh, R and Adhikari, R and Stone, HA}, title = {Flow-induced phase separation of active particles is controlled by boundary conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5403-5408}, pmid = {29735679}, issn = {1091-6490}, abstract = {Active particles, including swimming microorganisms, autophoretic colloids, and droplets, are known to self-organize into ordered structures at fluid-solid boundaries. The entrainment of particles in the attractive parts of their spontaneous flows has been postulated as a possible mechanism underlying this phenomenon. Here, combining experiments, theory, and numerical simulations, we demonstrate the validity of this flow-induced ordering mechanism in a suspension of active emulsion droplets. We show that the mechanism can be controlled, with a variety of resultant ordered structures, by simply altering hydrodynamic boundary conditions. Thus, for flow in Hele-Shaw cells, metastable lines or stable traveling bands can be obtained by varying the cell height. Similarly, for flow bounded by a plane, dynamic crystallites are formed. At a no-slip wall, the crystallites are characterized by a continuous out-of-plane flux of particles that circulate and re-enter at the crystallite edges, thereby stabilizing them. At an interface where the tangential stress vanishes, the crystallites are strictly 2D, with no out-of-plane flux. We rationalize these experimental results by calculating, in each case, the slow viscous flow produced by the droplets and the long-ranged, many-body active forces and torques between them. The results of numerical simulations of motion under the action of the active forces and torques are in excellent agreement with experiments. Our work elucidates the mechanism of flow-induced phase separation in active fluids, particularly active colloidal suspensions, and demonstrates its control by boundaries, suggesting routes to geometric and topological phenomena in an active matter.}, } @article {pmid29735678, year = {2018}, author = {Cui, Q and Li, Q and Geng, H and Chen, L and Ip, NY and Ke, Y and Yung, WH}, title = {Dopamine receptors mediate strategy abandoning via modulation of a specific prelimbic cortex-nucleus accumbens pathway in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4890-E4899}, doi = {10.1073/pnas.1717106115}, pmid = {29735678}, issn = {1091-6490}, mesh = {Animals ; Cerebral Cortex/cytology/*physiology ; Dopamine/*metabolism ; Limbic Lobe/cytology/*physiology ; Mice ; Neurons/cytology/*physiology ; Nucleus Accumbens/cytology/*physiology ; Receptors, Dopamine D1/*metabolism ; Receptors, Dopamine D2/*metabolism ; }, abstract = {The ability to abandon old strategies and adopt new ones is essential for survival in a constantly changing environment. While previous studies suggest the importance of the prefrontal cortex and some subcortical areas in the generation of strategy-switching flexibility, the fine neural circuitry and receptor mechanisms involved are not fully understood. In this study, we showed that optogenetic excitation and inhibition of the prelimbic cortex-nucleus accumbens (NAc) pathway in the mouse respectively enhances and suppresses strategy-switching ability in a cross-modal spatial-egocentric task. This ability is dependent on an intact dopaminergic tone in the NAc, as local dopamine denervation impaired the performance of the animal in the switching of tasks. In addition, based on a brain-slice preparation obtained from Drd2-EGFP BAC transgenic mice, we demonstrated direct innervation of D2 receptor-expressing medium spiny neurons (D2-MSNs) in the NAc by prelimbic cortical neurons, which is under the regulation by presynaptic dopamine receptors. While presynaptic D1-type receptor activation enhances the glutamatergic transmission from the prelimbic cortex to D2-MSNs, D2-type receptor activation suppresses this synaptic connection. Furthermore, manipulation of this pathway by optogenetic activation or administration of a D1-type agonist or a D2-type antagonist could restore impaired task-switching flexibility in mice with local NAc dopamine depletion; this restoration is consistent with the effects of knocking down the expression of specific dopamine receptors in the pathway. Our results point to a critical role of a specific prelimbic cortex-NAc subpathway in mediating strategy abandoning, allowing the switching from one strategy to another in problem solving.}, } @article {pmid29735677, year = {2018}, author = {Benson, CR and Maffeo, C and Fatila, EM and Liu, Y and Sheetz, EG and Aksimentiev, A and Singharoy, A and Flood, AH}, title = {Inchworm movement of two rings switching onto a thread by biased Brownian diffusion represent a three-body problem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9391-9396}, pmid = {29735677}, issn = {1091-6490}, support = {P41 GM104601/GM/NIGMS NIH HHS/United States ; R01 GM067887/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; *Biophysical Phenomena ; Catenanes/chemistry ; Diffusion ; Electrochemistry ; Kinetics ; *Models, Theoretical ; Molecular Dynamics Simulation ; *Motion ; Rotaxanes/chemistry ; *Thermodynamics ; }, abstract = {The coordinated motion of many individual components underpins the operation of all machines. However, despite generations of experience in engineering, understanding the motion of three or more coupled components remains a challenge, known since the time of Newton as the "three-body problem." Here, we describe, quantify, and simulate a molecular three-body problem of threading two molecular rings onto a linear molecular thread. Specifically, we use voltage-triggered reduction of a tetrazine-based thread to capture two cyanostar macrocycles and form a [3]pseudorotaxane product. As a consequence of the noncovalent coupling between the cyanostar rings, we find the threading occurs by an unexpected and rare inchworm-like motion where one ring follows the other. The mechanism was derived from controls, analysis of cyclic voltammetry (CV) traces, and Brownian dynamics simulations. CVs from two noncovalently interacting rings match that of two covalently linked rings designed to thread via the inchworm pathway, and they deviate considerably from the CV of a macrocycle designed to thread via a stepwise pathway. Time-dependent electrochemistry provides estimates of rate constants for threading. Experimentally derived parameters (energy wells, barriers, diffusion coefficients) helped determine likely pathways of motion with rate-kinetics and Brownian dynamics simulations. Simulations verified intercomponent coupling could be separated into ring-thread interactions for kinetics, and ring-ring interactions for thermodynamics to reduce the three-body problem to a two-body one. Our findings provide a basis for high-throughput design of molecular machinery with multiple components undergoing coupled motion.}, } @article {pmid29735676, year = {2018}, author = {Gosden, TP and Reddiex, AJ and Chenoweth, SF}, title = {Artificial selection reveals sex differences in the genetic basis of sexual attractiveness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5498-5503}, pmid = {29735676}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Choice Behavior ; Drosophila melanogaster/*genetics/physiology ; Female ; Male ; Mating Preference, Animal/*physiology ; Phenotype ; *Selection, Genetic ; Sexual Behavior, Animal/*physiology ; }, abstract = {Mutual mate choice occurs when males and females base mating decisions on shared traits. Despite increased awareness, the extent to which mutual choice drives phenotypic change remains poorly understood. When preferences in both sexes target the same traits, it is unclear how evolution will proceed and whether responses to sexual selection from male choice will match or oppose responses to female choice. Answering this question is challenging, as it requires understanding, genetic relationships between the traits targeted by choice, mating success, and, ultimately, fitness for both sexes. Addressing this, we applied artificial selection to the cuticular hydrocarbons of the fly Drosophila serrata that are targeted by mutual choice and tracked evolutionary changes in males and females alongside changes in mating success. After 10 generations, significant trait evolution occurred in both sexes, but intriguingly there were major sex differences in the associated fitness consequences. Sexually selected trait evolution in males led to a genetically based increase in male mating success. By contrast, although trait evolution also occurred in females, there was no change in mating success. Our results suggest that phenotypic sexual selection on females from male choice is environmentally, rather than genetically, generated. Thus, compared with female choice, male choice is at best a weak driver of signal trait evolution in this species. Instead, the evolution of apparent female ornamentation seems more likely due to a correlated response to sexual selection on males and possibly other forms of natural selection.}, } @article {pmid29735675, year = {2018}, author = {Mahatabuddin, S and Fukami, D and Arai, T and Nishimiya, Y and Shimizu, R and Shibazaki, C and Kondo, H and Adachi, M and Tsuda, S}, title = {Polypentagonal ice-like water networks emerge solely in an activity-improved variant of ice-binding protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5456-5461}, pmid = {29735675}, issn = {1091-6490}, mesh = {Animals ; Antifreeze Proteins/chemistry/genetics/*metabolism ; Binding Sites ; Biophysical Phenomena ; Carrier Proteins/chemistry/genetics/*metabolism ; Crystallography, X-Ray ; Fish Proteins/chemistry/genetics/*metabolism ; Fishes/metabolism ; *Freezing ; Ice/*analysis ; Mutation ; Protein Binding ; Protein Conformation ; Protein Isoforms ; Water/*chemistry/metabolism ; }, abstract = {Polypentagonal water networks were recently observed in a protein capable of binding to ice crystals, or ice-binding protein (IBP). To examine such water networks and clarify their role in ice-binding, we determined X-ray crystal structures of a 65-residue defective isoform of a Zoarcidae-derived IBP (wild type, WT) and its five single mutants (A20L, A20G, A20T, A20V, and A20I). Polypentagonal water networks composed of ∼50 semiclathrate waters were observed solely on the strongest A20I mutant, which appeared to include a tetrahedral water cluster exhibiting a perfect position match to the [Formula: see text] first prism plane of a single ice crystal. Inclusion of another symmetrical water cluster in the polypentagonal network showed a perfect complementarity to the waters constructing the [Formula: see text] pyramidal ice plane. The order of ice-binding strength was A20L < A20G < WT < A20T < A20V < A20I, where the top three mutants capable of binding to the first prism and the pyramidal ice planes commonly contained a bifurcated γ-CH3 group. These results suggest that a fine-tuning of the surface of Zoarcidae-derived IBP assisted by a side-chain group regulates the holding property of its polypentagonal water network, the function of which is to freeze the host protein to specific ice planes.}, } @article {pmid29735674, year = {2018}, author = {Esteve-Rudd, J and Hazim, RA and Diemer, T and Paniagua, AE and Volland, S and Umapathy, A and Williams, DS}, title = {Defective phagosome motility and degradation in cell nonautonomous RPE pathogenesis of a dominant macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5468-5473}, doi = {10.1073/pnas.1709211115}, pmid = {29735674}, issn = {1091-6490}, support = {F31 EY026805/EY/NEI NIH HHS/United States ; P30 EY000331/EY/NEI NIH HHS/United States ; R01 EY013408/EY/NEI NIH HHS/United States ; R01 EY027442/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Cell Movement ; Cells, Cultured ; *Disease Models, Animal ; Eye Proteins/*physiology ; Genes, Dominant ; Humans ; Macular Degeneration/genetics/metabolism/*pathology ; Membrane Proteins/*physiology ; Mice ; Mice, Transgenic ; *Mutation ; Phagosomes/metabolism/*pathology ; Photoreceptor Cells/metabolism/*pathology ; Retinal Pigment Epithelium/metabolism/*pathology ; }, abstract = {Stargardt macular dystrophy 3 (STGD3) is caused by dominant mutations in the ELOVL4 gene. Like other macular degenerations, pathogenesis within the retinal pigment epithelium (RPE) appears to contribute to the loss of photoreceptors from the central retina. However, the RPE does not express ELOVL4, suggesting photoreceptor cell loss in STGD3 occurs through two cell nonautonomous events: mutant photoreceptors first affect RPE cell pathogenesis, and then, second, RPE dysfunction leads to photoreceptor cell death. Here, we have investigated how the RPE pathology occurs, using a STGD3 mouse model in which mutant human ELOVL4 is expressed in the photoreceptors. We found that the mutant protein was aberrantly localized to the photoreceptor outer segment (POS), and that resulting POS phagosomes were degraded more slowly in the RPE. In cell culture, the mutant POSs are ingested by primary RPE cells normally, but the phagosomes are processed inefficiently, even by wild-type RPE. The mutant phagosomes excessively sequester RAB7A and dynein, and have impaired motility. We propose that the abnormal presence of ELOVL4 protein in POSs results in phagosomes that are defective in recruiting appropriate motor protein linkers, thus contributing to slower degradation because their altered motility results in slower basal migration and fewer productive encounters with endolysosomes. In the transgenic mouse retinas, the RPE accumulated abnormal-looking phagosomes and oxidative stress adducts; these pathological changes were followed by pathology in the neural retina. Our results indicate inefficient phagosome degradation as a key component of the first cell nonautonomous event underlying retinal degeneration due to mutant ELOVL4.}, } @article {pmid29735673, year = {2018}, author = {Kervezee, L and Cuesta, M and Cermakian, N and Boivin, DB}, title = {Simulated night shift work induces circadian misalignment of the human peripheral blood mononuclear cell transcriptome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5540-5545}, pmid = {29735673}, issn = {1091-6490}, support = {MOP-102724//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Circadian Rhythm/*physiology ; *Computer Simulation ; Female ; Humans ; Leukocytes, Mononuclear/*metabolism ; Male ; *Shift Work Schedule ; Sleep/*physiology ; Sleep Disorders, Circadian Rhythm/genetics/*physiopathology ; *Transcriptome ; Young Adult ; }, abstract = {Misalignment of the endogenous circadian timing system leads to disruption of physiological rhythms and may contribute to the development of the deleterious health effects associated with night shift work. However, the molecular underpinnings remain to be elucidated. Here, we investigated the effect of a 4-day simulated night shift work protocol on the circadian regulation of the human transcriptome. Repeated blood samples were collected over two 24-hour measurement periods from eight healthy subjects under highly controlled laboratory conditions before and 4 days after a 10-hour delay of their habitual sleep period. RNA was extracted from peripheral blood mononuclear cells to obtain transcriptomic data. Cosinor analysis revealed a marked reduction of significantly rhythmic transcripts in the night shift condition compared with baseline at group and individual levels. Subsequent analysis using a mixed-effects model selection approach indicated that this decrease is mainly due to dampened rhythms rather than to a complete loss of rhythmicity: 73% of transcripts rhythmically expressed at baseline remained rhythmic during the night shift condition with a similar phase relative to habitual bedtimes, but with lower amplitudes. Functional analysis revealed that key biological processes are affected by the night shift protocol, most notably the natural killer cell-mediated immune response and Jun/AP1 and STAT pathways. These results show that 4 days of simulated night shifts leads to a loss in temporal coordination between the human circadian transcriptome and the external environment and impacts biological processes related to the adverse health effects associated to night shift work.}, } @article {pmid29735672, year = {2018}, author = {Madgwick, PG and Stewart, B and Belcher, LJ and Thompson, CRL and Wolf, JB}, title = {Strategic investment explains patterns of cooperation and cheating in a microbe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4823-E4832}, pmid = {29735672}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; BB/M01035X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M007146/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; WT095643AIA//Wellcome Trust/United Kingdom ; }, mesh = {*Biological Evolution ; *Cooperative Behavior ; Dictyostelium/*physiology ; *Game Theory ; Individuality ; *Models, Biological ; Spores, Protozoan/*physiology ; }, abstract = {Contributing to cooperation is typically costly, while its rewards are often available to all members of a social group. So why should individuals be willing to pay these costs, especially if they could cheat by exploiting the investments of others? Kin selection theory broadly predicts that individuals should invest more into cooperation if their relatedness to group members is high (assuming they can discriminate kin from nonkin). To better understand how relatedness affects cooperation, we derived the ‟Collective Investment" game, which provides quantitative predictions for patterns of strategic investment depending on the level of relatedness. We then tested these predictions by experimentally manipulating relatedness (genotype frequencies) in mixed cooperative aggregations of the social amoeba Dictyostelium discoideum, which builds a stalk to facilitate spore dispersal. Measurements of stalk investment by natural strains correspond to the predicted patterns of relatedness-dependent strategic investment, wherein investment by a strain increases with its relatedness to the group. Furthermore, if overall group relatedness is relatively low (i.e., no strain is at high frequency in a group) strains face a scenario akin to the "Prisoner's Dilemma" and suffer from insufficient collective investment. We find that strains employ relatedness-dependent segregation to avoid these pernicious conditions. These findings demonstrate that simple organisms like D. discoideum are not restricted to being ‟cheaters" or ‟cooperators" but instead measure their relatedness to their group and strategically modulate their investment into cooperation accordingly. Consequently, all individuals will sometimes appear to cooperate and sometimes cheat due to the dynamics of strategic investing.}, } @article {pmid29735671, year = {2018}, author = {Bjerg, JT and Boschker, HTS and Larsen, S and Berry, D and Schmid, M and Millo, D and Tataru, P and Meysman, FJR and Wagner, M and Nielsen, LP and Schramm, A}, title = {Long-distance electron transport in individual, living cable bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5786-5791}, pmid = {29735671}, issn = {1091-6490}, support = {291650//European Research Council/International ; 294343//European Research Council/International ; }, mesh = {Bacteria/*chemistry/*metabolism ; Cytochromes/metabolism ; Electron Transport/*physiology ; Geologic Sediments/microbiology ; Oxidation-Reduction ; Oxygen/metabolism ; Spectrum Analysis, Raman ; Sulfides/metabolism ; }, abstract = {Electron transport within living cells is essential for energy conservation in all respiring and photosynthetic organisms. While a few bacteria transport electrons over micrometer distances to their surroundings, filaments of cable bacteria are hypothesized to conduct electric currents over centimeter distances. We used resonance Raman microscopy to analyze cytochrome redox states in living cable bacteria. Cable-bacteria filaments were placed in microscope chambers with sulfide as electron source and oxygen as electron sink at opposite ends. Along individual filaments a gradient in cytochrome redox potential was detected, which immediately broke down upon removal of oxygen or laser cutting of the filaments. Without access to oxygen, a rapid shift toward more reduced cytochromes was observed, as electrons were no longer drained from the filament but accumulated in the cellular cytochromes. These results provide direct evidence for long-distance electron transport in living multicellular bacteria.}, } @article {pmid29735670, year = {2018}, author = {Xiao, B and Stixrude, L}, title = {Critical vaporization of MgSiO3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5371-5376}, pmid = {29735670}, issn = {1091-6490}, abstract = {Inhomogeneous ab initio molecular dynamics simulations show that vaporization of MgSiO3 is incongruent and that the vapor phase is dominated by SiO and O2 molecules. The vapor is strongly depleted in Mg at low temperature and approaches the composition of the liquid near the critical point. We find that the liquid-vapor critical temperature ([Formula: see text] K) is much lower than assumed in hydrodynamic simulations, pointing to much more extensive supercritical fluid after the Moon-forming impact than previously thought. The structure of the near-critical liquid is very different from what has been studied previously and includes a significant fraction (10%) of molecular species SiO and O2.}, } @article {pmid29735669, year = {2018}, author = {Furini, S and Domene, C}, title = {Ion-triggered selectivity in bacterial sodium channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5450-5455}, pmid = {29735669}, issn = {1091-6490}, mesh = {Bacteria/*metabolism ; Bacterial Proteins/*metabolism ; Ion Channel Gating/*physiology ; Molecular Dynamics Simulation ; Potassium/*metabolism ; Sodium/*metabolism ; Sodium Channels/*metabolism ; Thermodynamics ; }, abstract = {Since the availability of the first crystal structure of a bacterial Na+ channel in 2011, understanding selectivity across this family of membrane proteins has been the subject of intense research efforts. Initially, free energy calculations based on molecular dynamics simulations revealed that although sodium ions can easily permeate the channel with their first hydration shell almost intact, the selectivity filter is too narrow for efficient conduction of hydrated potassium ions. This steric view of selectivity was subsequently questioned by microsecond atomic trajectories, which proved that the selectivity filter appears to the permeating ions as a highly degenerate, liquid-like environment. Although this liquid-like environment looks optimal for rapid conduction of Na+, it seems incompatible with efficient discrimination between similar ion species, such as Na+ and K+, through steric effects. Here extensive molecular dynamics simulations, combined with Markov state model analyses, reveal that at positive membrane potentials, potassium ions trigger a conformational change of the selectivity toward a nonconductive metastable state. It is this transition of the selectivity filter, and not steric effects, that prevents the outward flux of K+ at positive membrane potentials. This description of selectivity, triggered by the nature of the permeating ions, might have implications on the current understanding of how ion channels, and in particular bacterial Na+ channels, operate at the atomic scale.}, } @article {pmid29735668, year = {2018}, author = {Lai, X and Stiff, A and Duggan, M and Wesolowski, R and Carson, WE and Friedman, A}, title = {Modeling combination therapy for breast cancer with BET and immune checkpoint inhibitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5534-5539}, pmid = {29735668}, issn = {1091-6490}, support = {K24 CA093670/CA/NCI NIH HHS/United States ; P01 CA095426/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; B7-H1 Antigen/*antagonists & inhibitors ; Breast Neoplasms/*drug therapy/metabolism/pathology ; CTLA-4 Antigen/*antagonists & inhibitors ; Disease Models, Animal ; Drug Therapy, Combination ; Female ; Humans ; Mice ; *Models, Theoretical ; Proteins/*antagonists & inhibitors ; }, abstract = {CTLA-4 is an immune checkpoint expressed on active anticancer T cells. When it combines with its ligand B7 on dendritic cells, it inhibits the activity of the T cells. The Bromo- and Extra-Terminal (BET) protein family includes proteins that regulate the expression of key oncogenes and antiapoptotic proteins. BET inhibitor (BETi) has been shown to reduce the expression of MYC by suppressing its transcription factors and to down-regulate the hypoxic transcriptome response to VEGF-A. This paper develops a mathematical model of the treatment of cancer by combination therapy of BETi and CTLA-4 inhibitor. The model shows that the two drugs are positively correlated in the sense that the tumor volume decreases as the dose of each of the drugs is increased. The model also considers the effect of the combined therapy on levels of myeloid-derived suppressor cells (MDSCs) and the overexpression of TNF-α, which may predict gastrointestinal side effects of the combination.}, } @article {pmid29735667, year = {2018}, author = {Niu, H and Piaggi, PM and Invernizzi, M and Parrinello, M}, title = {Molecular dynamics simulations of liquid silica crystallization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5348-5352}, pmid = {29735667}, issn = {1091-6490}, abstract = {Silica is one of the most abundant minerals on Earth and is widely used in many fields. Investigating the crystallization of liquid silica by atomic simulations is of great importance to understand the crystallization mechanism; however, the high crystallization barrier and the tendency of silica to form glasses make such simulations very challenging. Here we have studied liquid silica crystallization to β-cristobalite with metadynamics, using X-ray diffraction (XRD) peak intensities as collective variables. The frequent transitions between solid and liquid of the biased runs demonstrate the highly successful use of the XRD peak intensities as collective variables, which leads to the convergence of the free-energy surface. By calculating the difference in free energy, we have estimated the melting temperature of β-cristobalite, which is in good agreement with the literature. The nucleation mechanism during the crystallization of liquid silica can be described by classical nucleation theory.}, } @article {pmid29735666, year = {2018}, author = {Frumkin, I and Lajoie, MJ and Gregg, CJ and Hornung, G and Church, GM and Pilpel, Y}, title = {Codon usage of highly expressed genes affects proteome-wide translation efficiency.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4940-E4949}, doi = {10.1073/pnas.1719375115}, pmid = {29735666}, issn = {1091-6490}, mesh = {Codon/*genetics ; Escherichia coli/genetics/growth & development/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Evolution, Molecular ; Open Reading Frames ; *Protein Biosynthesis ; Proteome/*analysis/genetics ; RNA, Transfer/genetics/*metabolism ; *Transcriptome ; }, abstract = {Although the genetic code is redundant, synonymous codons for the same amino acid are not used with equal frequencies in genomes, a phenomenon termed "codon usage bias." Previous studies have demonstrated that synonymous changes in a coding sequence can exert significant cis effects on the gene's expression level. However, whether the codon composition of a gene can also affect the translation efficiency of other genes has not been thoroughly explored. To study how codon usage bias influences the cellular economy of translation, we massively converted abundant codons to their rare synonymous counterpart in several highly expressed genes in Escherichia coli This perturbation reduces both the cellular fitness and the translation efficiency of genes that have high initiation rates and are naturally enriched with the manipulated codon, in agreement with theoretical predictions. Interestingly, we could alleviate the observed phenotypes by increasing the supply of the tRNA for the highly demanded codon, thus demonstrating that the codon usage of highly expressed genes was selected in evolution to maintain the efficiency of global protein translation.}, } @article {pmid29735665, year = {2018}, author = {Li, RC and Lin, CC and Ren, X and Wu, JS and Molday, LL and Molday, RS and Yau, KW}, title = {Ca2+-activated Cl current predominates in threshold response of mouse olfactory receptor neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5570-5575}, doi = {10.1073/pnas.1803443115}, pmid = {29735665}, issn = {1091-6490}, support = {R01 DC014941/DC/NIDCD NIH HHS/United States ; R01 EY002422/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Anoctamins/*physiology ; Brain/cytology/*physiology ; Calcium/*pharmacology ; Chlorides/*metabolism ; Cyclic AMP/pharmacology ; Cyclic Nucleotide-Gated Cation Channels/drug effects/*physiology ; Membrane Potentials/drug effects ; Mice ; Mice, Knockout ; Olfactory Receptor Neurons/cytology/drug effects/*physiology ; Patch-Clamp Techniques ; Signal Transduction/drug effects ; Smell/drug effects ; }, abstract = {In mammalian olfactory transduction, odorants activate a cAMP-mediated signaling pathway that leads to the opening of cyclic nucleotide-gated (CNG), nonselective cation channels and depolarization. The Ca2+ influx through open CNG channels triggers an inward current through Ca2+-activated Cl channels (ANO2), which is expected to produce signal amplification. However, a study on an Ano2-/- mouse line reported no elevation in the behavioral threshold of odorant detection compared with wild type (WT). Subsequent studies by others on the same Ano2-/- line, nonetheless, found subtle defects in olfactory behavior and some abnormal axonal projections from the olfactory receptor neurons (ORNs) to the olfactory bulb. As such, the question regarding signal amplification by the Cl current in WT mouse remains unsettled. Recently, with suction-pipette recording, we have successfully separated in frog ORNs the CNG and Cl currents during olfactory transduction and found the Cl current to predominate in the response down to the threshold of action-potential signaling to the brain. For better comparison with the mouse data by others, we have now carried out similar current-separation experiments on mouse ORNs. We found that the Cl current clearly also predominated in the mouse olfactory response at signaling threshold, accounting for ∼80% of the response. In the absence of the Cl current, we expect the threshold stimulus to increase by approximately sevenfold.}, } @article {pmid29735664, year = {2018}, author = {Hartle, J}, title = {Stephen Hawking (1942-2018): Toward a complete understanding of the universe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5309-5310}, doi = {10.1073/pnas.1806196115}, pmid = {29735664}, issn = {1091-6490}, } @article {pmid29735663, year = {2018}, author = {Said, I and Byrne, A and Serrano, V and Cardeno, C and Vollmers, C and Corbett-Detig, R}, title = {Linked genetic variation and not genome structure causes widespread differential expression associated with chromosomal inversions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5492-5497}, doi = {10.1073/pnas.1721275115}, pmid = {29735663}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Chromosome Inversion ; Chromosome Mapping ; Drosophila melanogaster/*genetics ; *Gene Expression Regulation ; Genetic Drift ; *Genetic Variation ; *Genome, Insect ; High-Throughput Nucleotide Sequencing ; Phenotype ; *Selection, Genetic ; }, abstract = {Chromosomal inversions are widely thought to be favored by natural selection because they suppress recombination between alleles that have higher fitness on the same genetic background or in similar environments. Nonetheless, few selected alleles have been characterized at the molecular level. Gene expression profiling provides a powerful way to identify functionally important variation associated with inversions and suggests candidate phenotypes. However, altered genome structure itself might also impact gene expression by influencing expression profiles of the genes proximal to inversion breakpoint regions or by modifying expression patterns genome-wide due to rearranging large regulatory domains. In natural inversions, genetic differentiation and genome structure are inextricably linked. Here, we characterize differential expression patterns associated with two chromosomal inversions found in natural Drosophila melanogaster populations. To isolate the impacts of genome structure, we engineered synthetic chromosomal inversions on controlled genetic backgrounds with breakpoints that closely match each natural inversion. We find that synthetic inversions have negligible effects on gene expression. Nonetheless, natural inversions have broad-reaching regulatory impacts in cis and trans Furthermore, we find that differentially expressed genes associated with both natural inversions are enriched for loci associated with immune response to bacterial pathogens. Our results support the idea that inversions in D. melanogaster experience natural selection to maintain associations between functionally related alleles to produce complex phenotypic outcomes.}, } @article {pmid29735662, year = {2018}, author = {Rokudai, S and Li, Y and Otaka, Y and Fujieda, M and Owens, DM and Christiano, AM and Nishiyama, M and Prives, C}, title = {STXBP4 regulates APC/C-mediated p63 turnover and drives squamous cell carcinogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4806-E4814}, doi = {10.1073/pnas.1718546115}, pmid = {29735662}, issn = {1091-6490}, support = {P01 CA087497/CA/NCI NIH HHS/United States ; R01 CA058316/CA/NCI NIH HHS/United States ; R37 CA058316/CA/NCI NIH HHS/United States ; }, mesh = {Anaphase-Promoting Complex-Cyclosome/genetics/*metabolism ; Animals ; Apoptosis ; Carcinogenesis/genetics/metabolism/*pathology ; Carcinoma, Squamous Cell/genetics/metabolism/*pathology ; Cell Cycle ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; *Gene Expression Regulation, Neoplastic ; Humans ; Keratinocytes/cytology/metabolism ; Mice ; Mice, SCID ; Proteolysis ; Transcription Factors/genetics/*metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; Vesicular Transport Proteins/genetics/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Levels of the N-terminally truncated isoform of p63 (ΔN p63), well documented to play a pivotal role in basal epidermal gene expression and epithelial maintenance, need to be strictly regulated. We demonstrate here that the anaphase-promoting complex/cyclosome (APC/C) complex plays an essential role in the ubiquitin-mediated turnover of ΔNp63α through the M-G1 phase. In addition, syntaxin-binding protein 4 (Stxbp4), which we previously discovered to bind to ΔNp63, can suppress the APC/C-mediated proteolysis of ΔNp63. Supporting the physiological relevance, of these interactions, both Stxbp4 and an APC/C-resistant version of ΔNp63α (RL7-ΔNp63α) inhibit the terminal differentiation process in 3D organotypic cultures. In line with this, both the stable RL7-ΔNp63α variant and Stxbp4 have oncogenic activity in soft agar and xenograft tumor assays. Notably as well, higher levels of Stxbp4 expression are correlated with the accumulation of ΔNp63 in human squamous cell carcinoma (SCC). Our study reveals that Stxbp4 drives the oncogenic potential of ΔNp63α and may provide a relevant therapeutic target for SCC.}, } @article {pmid29735661, year = {2018}, author = {Sun, J and Mooney, H and Wu, W and Tang, H and Tong, Y and Xu, Z and Huang, B and Cheng, Y and Yang, X and Wei, D and Zhang, F and Liu, J}, title = {Importing food damages domestic environment: Evidence from global soybean trade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5415-5419}, pmid = {29735661}, issn = {1091-6490}, mesh = {Agriculture/*economics/methods ; *Commerce ; Conservation of Natural Resources/*economics/methods ; Environmental Pollution/*prevention & control ; Food Supply/*economics ; Humans ; International Cooperation ; *Soybeans ; }, abstract = {Protecting the environment and enhancing food security are among the world's Sustainable Development Goals and greatest challenges. International food trade is an important mechanism to enhance food security worldwide. Nonetheless, it is widely concluded that in international food trade importing countries gain environmental benefits, while exporting countries suffer environmental problems by using land and other resources to produce food for exports. Our study shows that international food trade can also lead to environmental pollution in importing countries. At the global level, our metaanalysis indicates that there was increased nitrogen (N) pollution after much farmland for domestically cultivated N-fixing soybeans in importing countries was converted to grow high N-demanding crops (wheat, corn, rice, and vegetables). The findings were further verified by an intensive study at the regional level in China, the largest soybean-importing country, where the conversion of soybean lands to corn fields and rice paddies has also led to N pollution. Our study provides a sharp contrast to the conventional wisdom that only exports contribute substantially to environmental woes. Our results suggest the need to evaluate environmental consequences of international trade of all other major goods and products in all importing countries, which have significant implications for fundamental rethinking in global policy-making and debates on environmental responsibilities among consumers, producers, and traders across the world.}, } @article {pmid29735660, year = {2018}, author = {Elsner, D and Meusemann, K and Korb, J}, title = {Longevity and transposon defense, the case of termite reproductives.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5504-5509}, doi = {10.1073/pnas.1804046115}, pmid = {29735660}, issn = {1091-6490}, mesh = {Animals ; *DNA Transposable Elements ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing ; Isoptera/*genetics ; *Longevity ; RNA, Small Interfering/*genetics ; *Reproduction ; }, abstract = {Social insects are promising new models in aging research. Within single colonies, longevity differences of several magnitudes exist that can be found elsewhere only between different species. Reproducing queens (and, in termites, also kings) can live for several decades, whereas sterile workers often have a lifespan of a few weeks only. We studied aging in the wild in a highly social insect, the termite Macrotermes bellicosus, which has one of the most pronounced longevity differences between reproductives and workers. We show that gene-expression patterns differed little between young and old reproductives, implying negligible aging. By contrast, old major workers had many genes up-regulated that are related to transposable elements (TEs), which can cause aging. Strikingly, genes from the PIWI-interacting RNA (piRNA) pathway, which are generally known to silence TEs in the germline of multicellular animals, were down-regulated only in old major workers but not in reproductives. Continued up-regulation of the piRNA defense commonly found in the germline of animals can explain the long life of termite reproductives, implying somatic cooption of germline defense during social evolution. This presents a striking germline/soma analogy as envisioned by the superorganism concept: the reproductives and workers of a colony reflect the germline and soma of multicellular animals, respectively. Our results provide support for the disposable soma theory of aging.}, } @article {pmid29735659, year = {2018}, author = {Wan, S and Li, Y and Mu, J and Aliev, AE and Fang, S and Kotov, NA and Jiang, L and Cheng, Q and Baughman, RH}, title = {Sequentially bridged graphene sheets with high strength, toughness, and electrical conductivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5359-5364}, pmid = {29735659}, issn = {1091-6490}, abstract = {We here show that infiltrated bridging agents can convert inexpensively fabricated graphene platelet sheets into high-performance materials, thereby avoiding the need for a polymer matrix. Two types of bridging agents were investigated for interconnecting graphene sheets, which attach to sheets by either π-π bonding or covalent bonding. When applied alone, the π-π bonding agent is most effective. However, successive application of the optimized ratio of π-π bonding and covalent bonding agents provides graphene sheets with the highest strength, toughness, fatigue resistance, electrical conductivity, electromagnetic interference shielding efficiency, and resistance to ultrasonic dissolution. Raman spectroscopy measurements of stress transfer to graphene platelets allow us to decipher the mechanisms of property improvement. In addition, the degree of orientation of graphene platelets increases with increasing effectiveness of the bonding agents, and the interlayer spacing increases. Compared with other materials that are strong in all directions within a sheet, the realized tensile strength (945 MPa) of the resin-free graphene platelet sheets was higher than for carbon nanotube or graphene platelet composites, and comparable to that of commercially available carbon fiber composites. The toughness of these composites, containing the combination of π-π bonding and covalent bonding, was much higher than for these other materials having high strengths for all in-plane directions, thereby opening the path to materials design of layered nanocomposites using multiple types of quantitatively engineered chemical bonds between nanoscale building blocks.}, } @article {pmid29735658, year = {2018}, author = {Kim, J and Xia, A and Grillet, N and Applegate, BE and Oghalai, JS}, title = {Osmotic stabilization prevents cochlear synaptopathy after blast trauma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4853-E4860}, pmid = {29735658}, issn = {1091-6490}, support = {P30 DC010363/DC/NIDCD NIH HHS/United States ; R01 DC013774/DC/NIDCD NIH HHS/United States ; R01 DC014450/DC/NIDCD NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Auditory Threshold ; Cochlea/*physiopathology ; Cochlear Diseases/physiopathology/*prevention & control ; Endolymphatic Hydrops/*physiopathology ; Hair Cells, Auditory/*pathology ; Hearing Loss, Noise-Induced/physiopathology/*prevention & control ; Mice ; Noise/*adverse effects ; *Osmosis ; }, abstract = {Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K+-dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure.}, } @article {pmid29735657, year = {2018}, author = {Augustyniak, R and Kay, LE}, title = {Cotranslocational processing of the protein substrate calmodulin by an AAA+ unfoldase occurs via unfolding and refolding intermediates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4786-E4795}, pmid = {29735657}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Adenosine Triphosphate/metabolism ; Archaeal Proteins/*chemistry/*metabolism ; Calmodulin/*metabolism ; Models, Molecular ; Protein Conformation ; *Protein Folding ; *Protein Unfolding ; Thermoplasma/*enzymology ; Valosin Containing Protein/*chemistry/*metabolism ; }, abstract = {Protein remodeling by AAA+ enzymes is central for maintaining proteostasis in a living cell. However, a detailed structural description of how this is accomplished at the level of the substrate molecules that are acted upon is lacking. Here, we combine chemical cross-linking and methyl transverse relaxation-optimized NMR spectroscopy to study, at atomic resolution, the stepwise unfolding and subsequent refolding of the two-domain substrate calmodulin by the VAT AAA+ unfoldase from Thermoplasma acidophilum By engineering intermolecular disulphide bridges between the substrate and VAT we trap the substrate at different stages of translocation, allowing structural studies throughout the translocation process. Our results show that VAT initiates substrate translocation by pulling on intrinsically unstructured N or C termini of substrate molecules without showing specificity for a particular amino acid sequence. Although the B1 domain of protein G is shown to unfold cooperatively, translocation of calmodulin leads to the formation of intermediates, and these differ on an individual domain level in a manner that depends on whether pulling is from the N or C terminus. The approach presented generates an atomic resolution picture of substrate unfolding and subsequent refolding by unfoldases that can be quite different from results obtained via in vitro denaturation experiments.}, } @article {pmid29735656, year = {2018}, author = {Xu, X and Kanai, R and Nakazawa, N and Wang, L and Toyoshima, C and Yanagida, M}, title = {Suppressor mutation analysis combined with 3D modeling explains cohesin's capacity to hold and release DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4833-E4842}, pmid = {29735656}, issn = {1091-6490}, mesh = {Cell Cycle Proteins/*chemistry/genetics/*metabolism ; Chromatids/physiology ; Chromosomal Proteins, Non-Histone/*chemistry/genetics/*metabolism ; Chromosome Segregation ; DNA, Fungal/genetics/*metabolism ; Models, Molecular ; *Mutation ; Nuclear Proteins/genetics/*metabolism ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Protein Conformation ; Protein Subunits ; Schizosaccharomyces/*genetics/growth & development/metabolism ; Schizosaccharomyces pombe Proteins/*chemistry/genetics/*metabolism ; Suppression, Genetic ; }, abstract = {Cohesin is a fundamental protein complex that holds sister chromatids together. Separase protease cleaves a cohesin subunit Rad21/SCC1, causing the release of cohesin from DNA to allow chromosome segregation. To understand the functional organization of cohesin, we employed next-generation whole-genome sequencing and identified numerous extragenic suppressors that overcome either inactive separase/Cut1 or defective cohesin in the fission yeast Schizosaccharomyces pombe Unexpectedly, Cut1 is dispensable if suppressor mutations cause disorders of interfaces among essential cohesin subunits Psm1/SMC1, Psm3/SMC3, Rad21/SCC1, and Mis4/SCC2, the crystal structures of which suggest physical and functional impairment at the interfaces of Psm1/3 hinge, Psm1 head-Rad21, or Psm3 coiled coil-Rad21. Molecular-dynamics analysis indicates that the intermolecular β-sheets in the cohesin hinge of cut1 suppressor mutants remain intact, but a large mobility change occurs at the coiled coil bound to the hinge. In contrast, suppressors of rad21-K1 occur in either the head ATPase domains or the Psm3 coiled coil that interacts with Rad21. Suppressors of mis4-G1326E reside in the head of Psm3/1 or the intragenic domain of Mis4. These may restore the binding of cohesin to DNA. Evidence is provided that the head and hinge of SMC subunits are proximal, and that they coordinate to form arched coils that can hold or release DNA by altering the angles made by the arched coiled coils. By combining molecular modeling with suppressor sequence analysis, we propose a cohesin structure designated the "hold-and-release" model, which may be considered as an alternative to the prevailing "ring" model.}, } @article {pmid29735655, year = {2018}, author = {Ren, Q and Ma, M and Yang, J and Nonaka, R and Yamaguchi, A and Ishikawa, KI and Kobayashi, K and Murayama, S and Hwang, SH and Saiki, S and Akamatsu, W and Hattori, N and Hammock, BD and Hashimoto, K}, title = {Soluble epoxide hydrolase plays a key role in the pathogenesis of Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {25}, pages = {E5815-E5823}, pmid = {29735655}, issn = {1091-6490}, support = {P42 ES004699/ES/NIEHS NIH HHS/United States ; R01 ES002710/ES/NIEHS NIH HHS/United States ; }, mesh = {1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine/pharmacology ; Animals ; Cell Line ; Corpus Striatum/metabolism/pathology ; Disease Models, Animal ; Dopaminergic Neurons/drug effects/pathology ; Epoxide Hydrolases/*metabolism ; HEK293 Cells ; Humans ; Lewy Bodies/drug effects/metabolism/pathology ; MPTP Poisoning/metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Nerve Degeneration/metabolism/pathology ; Parkinson Disease/*metabolism/*pathology ; RNA, Messenger/metabolism ; alpha-Synuclein/metabolism ; }, abstract = {Parkinson's disease (PD) is characterized as a chronic and progressive neurodegenerative disorder, and the deposition of specific protein aggregates of α-synuclein, termed Lewy bodies, is evident in multiple brain regions of PD patients. Although there are several available medications to treat PD symptoms, these medications do not prevent the progression of the disease. Soluble epoxide hydrolase (sEH) plays a key role in inflammation associated with the pathogenesis of PD. Here we found that MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)-induced neurotoxicity in the mouse striatum was attenuated by subsequent repeated administration of TPPU, a potent sEH inhibitor. Furthermore, deletion of the sEH gene protected against MPTP-induced neurotoxicity, while overexpression of sEH in the striatum significantly enhanced MPTP-induced neurotoxicity. Moreover, the expression of the sEH protein in the striatum from MPTP-treated mice or postmortem brain samples from patients with dementia of Lewy bodies (DLB) was significantly higher compared with control groups. Interestingly, there was a positive correlation between sEH expression and phosphorylation of α-synuclein in the striatum. Oxylipin analysis showed decreased levels of 8,9-epoxy-5Z,11Z,14Z-eicosatrienoic acid in the striatum of MPTP-treated mice, suggesting increased activity of sEH in this region. Interestingly, the expression of sEH mRNA in human PARK2 iPSC-derived neurons was higher than that of healthy control. Treatment with TPPU protected against apoptosis in human PARK2 iPSC-derived dopaminergic neurons. These findings suggest that increased activity of sEH in the striatum plays a key role in the pathogenesis of neurodegenerative disorders such as PD and DLB. Therefore, sEH may represent a promising therapeutic target for α-synuclein-related neurodegenerative disorders.}, } @article {pmid29735654, year = {2018}, author = {Zanos, TP and Silverman, HA and Levy, T and Tsaava, T and Battinelli, E and Lorraine, PW and Ashe, JM and Chavan, SS and Tracey, KJ and Bouton, CE}, title = {Identification of cytokine-specific sensory neural signals by decoding murine vagus nerve activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4843-E4852}, pmid = {29735654}, issn = {1091-6490}, support = {P01 AI102852/AI/NIAID NIH HHS/United States ; R35 GM118182/GM/NIGMS NIH HHS/United States ; }, mesh = {Action Potentials/drug effects ; Animals ; Bayes Theorem ; Interleukin-1beta/*pharmacology ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Receptors, Interleukin-1 Type I/*physiology ; Sensory Receptor Cells/cytology/drug effects/*physiology ; TRPV Cation Channels/*physiology ; Tumor Necrosis Factor-alpha/*pharmacology ; Vagus Nerve/cytology/drug effects/*physiology ; }, abstract = {The nervous system maintains physiological homeostasis through reflex pathways that modulate organ function. This process begins when changes in the internal milieu (e.g., blood pressure, temperature, or pH) activate visceral sensory neurons that transmit action potentials along the vagus nerve to the brainstem. IL-1β and TNF, inflammatory cytokines produced by immune cells during infection and injury, and other inflammatory mediators have been implicated in activating sensory action potentials in the vagus nerve. However, it remains unclear whether neural responses encode cytokine-specific information. Here we develop methods to isolate and decode specific neural signals to discriminate between two different cytokines. Nerve impulses recorded from the vagus nerve of mice exposed to IL-1β and TNF were sorted into groups based on their shape and amplitude, and their respective firing rates were computed. This revealed sensory neural groups responding specifically to TNF and IL-1β in a dose-dependent manner. These cytokine-mediated responses were subsequently decoded using a Naive Bayes algorithm that discriminated between no exposure and exposures to IL-1β and TNF (mean successful identification rate 82.9 ± 17.8%, chance level 33%). Recordings obtained in IL-1 receptor-KO mice were devoid of IL-1β-related signals but retained their responses to TNF. Genetic ablation of TRPV1 neurons attenuated the vagus neural signals mediated by IL-1β, and distal lidocaine nerve block attenuated all vagus neural signals recorded. The results obtained in this study using the methodological framework suggest that cytokine-specific information is present in sensory neural signals within the vagus nerve.}, } @article {pmid29735653, year = {2018}, author = {Solórzano Kraemer, MM and Delclòs, X and Clapham, ME and Arillo, A and Peris, D and Jäger, P and Stebner, F and Peñalver, E}, title = {Arthropods in modern resins reveal if amber accurately recorded forest arthropod communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {26}, pages = {6739-6744}, pmid = {29735653}, issn = {1091-6490}, mesh = {Amber/*history ; Animals ; *Arthropods/classification/physiology ; Behavior, Animal ; *Biodiversity ; Ecology ; Ecosystem ; *Forests ; *Fossils ; History, Ancient ; Hymenaea ; Madagascar ; *Resins, Plant ; Species Specificity ; }, abstract = {Amber is an organic multicompound derivative from the polymerization of resin of diverse higher plants. Compared with other modes of fossil preservation, amber records the anatomy of and ecological interactions between ancient soft-bodied organisms with exceptional fidelity. However, it is currently suggested that ambers do not accurately record the composition of arthropod forest paleocommunities, due to crucial taphonomic biases. We evaluated the effects of taphonomic processes on arthropod entrapment by resin from the plant Hymenaea, one of the most important resin-producing trees and a producer of tropical Cenozoic ambers and Anthropocene (or subfossil) resins. We statistically compared natural entrapment by Hymenaea verrucosa tree resin with the ensemble of arthropods trapped by standardized entomological traps around the same tree species. Our results demonstrate that assemblages in resin are more similar to those from sticky traps than from malaise traps, providing an accurate representation of the arthropod fauna living in or near the resiniferous tree, but not of entire arthropod forest communities. Particularly, arthropod groups such as Lepidoptera, Collembola, and some Diptera are underrepresented in resins. However, resin assemblages differed slightly from sticky traps, perhaps because chemical compounds in the resins attract or repel specific insect groups. Ground-dwelling or flying arthropods that use the tree-trunk habitat for feeding or reproduction are also well represented in the resin assemblages, implying that fossil inclusions in amber can reveal fundamental information about biology of the past. These biases have implications for the paleoecological interpretation of the fossil record, principally of Cenozoic amber with angiosperm origin.}, } @article {pmid29735652, year = {2018}, author = {Lei, W and Ren, W and Ohmoto, M and Urban, JF and Matsumoto, I and Margolskee, RF and Jiang, P}, title = {Activation of intestinal tuft cell-expressed Sucnr1 triggers type 2 immunity in the mouse small intestine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5552-5557}, pmid = {29735652}, issn = {1091-6490}, support = {G20 OD020296/OD/NIH HHS/United States ; P30 DC011735/DC/NIDCD NIH HHS/United States ; R01 DC014105/DC/NIDCD NIH HHS/United States ; S10 OD018125/OD/NIH HHS/United States ; }, mesh = {Animals ; Cell Proliferation/drug effects ; Cells, Cultured ; Epithelial Cells/drug effects/*immunology/metabolism/pathology ; Female ; Goblet Cells/*immunology/metabolism/pathology ; Immunity, Mucosal/drug effects/*immunology ; Intestine, Small/drug effects/*immunology/metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Microbiota ; Nippostrongylus/*immunology ; Receptors, G-Protein-Coupled/*physiology ; Strongylida Infections/parasitology ; Succinic Acid/*administration & dosage ; }, abstract = {The hallmark features of type 2 mucosal immunity include intestinal tuft and goblet cell expansion initiated by tuft cell activation. How infectious agents that induce type 2 mucosal immunity are detected by tuft cells is unknown. Published microarray analysis suggested that succinate receptor 1 (Sucnr1) is specifically expressed in tuft cells. Thus, we hypothesized that the succinate-Sucnr1 axis may be utilized by tuft cells to detect certain infectious agents. Here we confirmed that Sucnr1 is specifically expressed in intestinal tuft cells but not in other types of intestinal epithelial cells, and demonstrated that dietary succinate induces tuft and goblet cell hyperplasia via Sucnr1 and the tuft cell-expressed chemosensory signaling elements gustducin and Trpm5. Conventional mice with a genetic Sucnr1 deficiency (Sucnr1-/-) showed diminished immune responses to treatment with polyethylene glycol and streptomycin, which are known to enhance microbiota-derived succinate, but responded normally to inoculation with the parasitic worm Nippostrongylus brasiliensis that also produces succinate. Thus, Sucnr1 is required for microbiota-induced but not for a generalized worm-induced type 2 immunity.}, } @article {pmid29735651, year = {2018}, author = {Labro, AJ and Cortes, DM and Tilegenova, C and Cuello, LG}, title = {Inverted allosteric coupling between activation and inactivation gates in K+ channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5426-5431}, pmid = {29735651}, issn = {1091-6490}, support = {R01 GM097159/GM/NIGMS NIH HHS/United States ; }, mesh = {Alanine/chemistry/genetics/metabolism ; Allosteric Regulation ; Bacterial Proteins/chemistry/genetics/metabolism ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Ion Channel Gating/*physiology ; Models, Molecular ; Mutation ; Potassium/*metabolism ; Potassium Channels/*chemistry/genetics/*metabolism ; Protein Conformation ; Threonine/chemistry/genetics/metabolism ; }, abstract = {The selectivity filter and the activation gate in potassium channels are functionally and structurally coupled. An allosteric coupling underlies C-type inactivation coupled to activation gating in this ion-channel family (i.e., opening of the activation gate triggers the collapse of the channel's selectivity filter). We have identified the second Threonine residue within the TTVGYGD signature sequence of K+ channels as a crucial residue for this allosteric communication. A Threonine to Alanine substitution at this position was studied in three representative members of the K+-channel family. Interestingly, all of the mutant channels exhibited lack of C-type inactivation gating and an inversion of their allosteric coupling (i.e., closing of the activation gate collapses the channel's selectivity filter). A state-dependent crystallographic study of KcsA-T75A proves that, on activation, the selectivity filter transitions from a nonconductive and deep C-type inactivated conformation to a conductive one. Finally, we provide a crystallographic demonstration that closed-state inactivation can be achieved by the structural collapse of the channel's selectivity filter.}, } @article {pmid29735650, year = {2018}, author = {Selim, KA and Haase, F and Hartmann, MD and Hagemann, M and Forchhammer, K}, title = {PII-like signaling protein SbtB links cAMP sensing with cyanobacterial inorganic carbon response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4861-E4869}, doi = {10.1073/pnas.1803790115}, pmid = {29735650}, issn = {1091-6490}, mesh = {Acclimatization ; Bacterial Proteins/*metabolism ; *Biological Evolution ; Carbon Compounds, Inorganic/*metabolism ; Crystallography, X-Ray ; Cyanobacteria/growth & development/*metabolism ; Cyclic AMP/*metabolism ; Photosynthesis ; Protein Phosphatase 2/*metabolism ; Signal Transduction ; }, abstract = {Cyanobacteria are phototrophic prokaryotes that evolved oxygenic photosynthesis ∼2.7 billion y ago and are presently responsible for ∼10% of total global photosynthetic production. To cope with the evolutionary pressure of dropping ambient CO2 concentrations, they evolved a CO2-concentrating mechanism (CCM) to augment intracellular inorganic carbon (Ci) levels for efficient CO2 fixation. However, how cyanobacteria sense the fluctuation in Ci is poorly understood. Here we present biochemical, structural, and physiological insights into SbtB, a unique PII-like signaling protein, which provides new insights into Ci sensing. SbtB is highly conserved in cyanobacteria and is coexpressed with CCM genes. The SbtB protein from the cyanobacterium Synechocystis sp. PCC 6803 bound a variety of adenosine nucleotides, including the second messenger cAMP. Cocrystal structures unraveled the individual binding modes of trimeric SbtB with AMP and cAMP. The nucleotide-binding pocket is located between the subunit clefts of SbtB, perfectly matching the structure of canonical PII proteins. This clearly indicates that proteins of the PII superfamily arose from a common ancestor, whose structurally conserved nucleotide-binding pocket has evolved to sense different adenyl nucleotides for various signaling functions. Moreover, we provide physiological and biochemical evidence for the involvement of SbtB in Ci acclimation. Collectively, our results suggest that SbtB acts as a Ci sensor protein via cAMP binding, highlighting an evolutionarily conserved role for cAMP in signaling the cellular carbon status.}, } @article {pmid29735649, year = {2018}, author = {Liston, SD and McMahon, SA and Le Bas, A and Suits, MDL and Naismith, JH and Whitfield, C}, title = {Periplasmic depolymerase provides insight into ABC transporter-dependent secretion of bacterial capsular polysaccharides.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4870-E4879}, pmid = {29735649}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; FDN_148364//CIHR/Canada ; 100209/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {ATP-Binding Cassette Transporters/chemistry/*metabolism ; Bacterial Proteins/chemistry/*metabolism ; Biological Transport ; Burkholderia/*enzymology ; Lyases/chemistry/*metabolism ; Periplasm/*enzymology ; Phylogeny ; Polysaccharides, Bacterial/*metabolism ; Protein Conformation ; }, abstract = {Capsules are surface layers of hydrated capsular polysaccharides (CPSs) produced by many bacteria. The human pathogen Salmonella enterica serovar Typhi produces "Vi antigen" CPS, which contributes to virulence. In a conserved strategy used by bacteria with diverse CPS structures, translocation of Vi antigen to the cell surface is driven by an ATP-binding cassette (ABC) transporter. These transporters are engaged in heterooligomeric complexes proposed to form an enclosed translocation conduit to the cell surface, allowing the transporter to power the entire process. We identified Vi antigen biosynthesis genetic loci in genera of the Burkholderiales, which are paradoxically distinguished from S. Typhi by encoding VexL, a predicted pectate lyase homolog. Biochemical analyses demonstrated that VexL is an unusual metal-independent endolyase with an acidic pH optimum that is specific for O-acetylated Vi antigen. A 1.22-Å crystal structure of the VexL-Vi antigen complex revealed features which distinguish common secreted catabolic pectate lyases from periplasmic VexL, which participates in cell-surface assembly. VexL possesses a right-handed parallel β-superhelix, of which one face forms an electropositive glycan-binding groove with an extensive hydrogen bonding network that includes Vi antigen acetyl groups and confers substrate specificity. VexL provided a probe to interrogate conserved features of the ABC transporter-dependent export model. When introduced into S Typhi, VexL localized to the periplasm and degraded Vi antigen. In contrast, a cytosolic derivative had no effect unless export was disrupted. These data provide evidence that CPS assembled in ABC transporter-dependent systems is actually exposed to the periplasm during envelope translocation.}, } @article {pmid29735648, year = {2018}, author = {}, title = {Correction for Jenkitkasemwong et al., SLC39A14 deficiency alters manganese homeostasis and excretion resulting in brain manganese accumulation and motor deficits in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4730}, doi = {10.1073/pnas.1806613115}, pmid = {29735648}, issn = {1091-6490}, } @article {pmid29735647, year = {2018}, author = {}, title = {Correction for Sanjak et al., Evidence of directional and stabilizing selection in contemporary humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4732}, doi = {10.1073/pnas.1806837115}, pmid = {29735647}, issn = {1091-6490}, } @article {pmid29735646, year = {2018}, author = {Obadia, B and Keebaugh, ES and Yamada, R and Ludington, WB and Ja, WW}, title = {Diet influences host-microbiota associations in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4547-E4548}, pmid = {29735646}, issn = {1091-6490}, mesh = {Animals ; Diet ; *Drosophila ; Drosophila melanogaster ; Gastrointestinal Tract ; *Microbiota ; }, } @article {pmid29735640, year = {2018}, author = {Hellen, CUT}, title = {Translation Termination and Ribosome Recycling in Eukaryotes.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a032656}, pmid = {29735640}, issn = {1943-0264}, support = {R01 AI123406/AI/NIAID NIH HHS/United States ; }, abstract = {Termination of mRNA translation occurs when a stop codon enters the A site of the ribosome, and in eukaryotes is mediated by release factors eRF1 and eRF3, which form a ternary eRF1/eRF3-guanosine triphosphate (GTP) complex. eRF1 recognizes the stop codon, and after hydrolysis of GTP by eRF3, mediates release of the nascent peptide. The post-termination complex is then disassembled, enabling its constituents to participate in further rounds of translation. Ribosome recycling involves splitting of the 80S ribosome by the ATP-binding cassette protein ABCE1 to release the 60S subunit. Subsequent dissociation of deacylated transfer RNA (tRNA) and messenger RNA (mRNA) from the 40S subunit may be mediated by initiation factors (priming the 40S subunit for initiation), by ligatin (eIF2D) or by density-regulated protein (DENR) and multiple copies in T-cell lymphoma-1 (MCT1). These events may be subverted by suppression of termination (yielding carboxy-terminally extended read-through polypeptides) or by interruption of recycling, leading to reinitiation of translation near the stop codon.}, } @article {pmid29735639, year = {2018}, author = {Merrick, WC and Pavitt, GD}, title = {Protein Synthesis Initiation in Eukaryotic Cells.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, doi = {10.1101/cshperspect.a033092}, pmid = {29735639}, issn = {1943-0264}, abstract = {This review summarizes our current understanding of the major pathway for the initiation phase of protein synthesis in eukaryotic cells, with a focus on recent advances. We describe the major scanning or messenger RNA (mRNA) m7G cap-dependent mechanism, which is a highly coordinated and stepwise regulated process that requires the combined action of at least 12 distinct translation factors with initiator transfer RNA (tRNA), ribosomes, and mRNAs. We limit our review to studies involving either mammalian or budding yeast cells and factors, as these represent the two best-studied experimental systems, and only include a reference to other organisms where particular insight has been gained. We close with a brief description of what we feel are some of the major unknowns in eukaryotic initiation.}, } @article {pmid29735283, year = {2018}, author = {Kramara, J and Osia, B and Malkova, A}, title = {Break-Induced Replication: The Where, The Why, and The How.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {7}, pages = {518-531}, doi = {10.1016/j.tig.2018.04.002}, pmid = {29735283}, issn = {0168-9525}, abstract = {Break-induced replication (BIR) is a pathway that repairs one-ended double-strand breaks (DSBs). For decades, yeast model systems offered the only opportunities to study eukaryotic BIR. These studies described an unusual mode of BIR synthesis that is carried out by a migrating bubble and shows conservative inheritance of newly synthesized DNA, leading to genomic instabilities like those associated with cancer in humans. Yet, evidence of BIR functioning in mammals or during repair of other DNA breaks has been missing. Recent studies have uncovered multiple examples of BIR working in replication restart and repair of eroded telomeres in yeast and mammals, as well as some unexpected findings, including the RAD51 independence of BIR. Strong interest remains in determining the variations in molecular mechanisms that drive and regulate BIR in different genetic backgrounds, across organisms, and particularly in the context of human disease.}, } @article {pmid29733997, year = {2018}, author = {Kalkreuter, E and Williams, GJ}, title = {Engineering enzymatic assembly lines for the production of new antimicrobials.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {140-148}, doi = {10.1016/j.mib.2018.04.005}, pmid = {29733997}, issn = {1879-0364}, abstract = {A large portion of natural products are biosynthesized by the polyketide synthase and non-ribosomal peptide synthetase enzymatic assembly lines. Recent advancements in the study of these megasynthases has led to many new examples that demonstrate the production of non-natural natural products. The field is likely nearing the ability to design and build new biosynthetic pathways de novo. We discuss the various recent approaches taken towards this goal, focusing on the installation of new substrates, the swapping of enzymatic domains and modules, and the impact of metabolic engineering and synthetic biology. We also address the challenges remaining alongside the many successes in this area.}, } @article {pmid29733978, year = {2018}, author = {Kobayashi, G and Goto, R and Takano, T and Kojima, S}, title = {Molecular phylogeny of Maldanidae (Annelida): Multiple losses of tube-capping plates and evolutionary shifts in habitat depth.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {332-344}, doi = {10.1016/j.ympev.2018.04.036}, pmid = {29733978}, issn = {1095-9513}, abstract = {Inter-familial relationships of the phylum Annelida have been widely studied using molecular phylogenetic/genomic approaches; however, intra-familial relationships remain scarcely investigated in most annelid families. The Maldanidae (bamboo worms) comprise more than 280 species of 40 genera and six subfamilies that occur in various environments from intertidal to hadal zones. Within this family, the taxon Maldanoplaca, which consists of four subfamilies (Maldaninae, Notoproctinae, Nicomachinae, and Euclymeninae), was proposed based on the presence of cephalic and anal plates. Phylogenetic relationships within the family remain largely undetermined based on molecular data. In this study, we reconstructed a molecular phylogeny using 52 maldanid species from six subfamilies based on two nuclear genes (18S rDNA and 28S rDNA) and two mitochondrial genes (16S rDNA and COI). Our analysis confirmed the monophyly of the subfamilies Rhodininae, Maldaninae, Lumbriclymeninae, and Nicomachinae, but neither Maldanoplaca nor the subfamily Euclymeninae were recovered as monophyletic. Nicomachinae was clustered within Euclymeninae. Ancestral state reconstruction suggested that cephalic plates were lost at least three times, despite the functional importance of capping tubes, and that anal plates were lost once. Mapping habitat depth on the phylogenetic tree suggested that habitat shifts among depth zones frequently occurred in distinct maldanid lineages.}, } @article {pmid29733977, year = {2018}, author = {Bauret, L and Field, AR and Gaudeul, M and Selosse, MA and Rouhan, G}, title = {First insights on the biogeographical history of Phlegmariurus (Lycopodiaceae), with a focus on Madagascar.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {488-501}, doi = {10.1016/j.ympev.2018.05.004}, pmid = {29733977}, issn = {1095-9513}, mesh = {Fossils ; Islands ; Lycopodiaceae/*classification/genetics ; Madagascar ; Phylogeny ; Phylogeography ; Plastids/genetics ; Sequence Analysis, DNA ; }, abstract = {We explored the biogeographical history of a group of spore-bearing plants focusing on Phlegmariurus (Lycopodiaceae), a genus of lycophytes comprising ca. 250 species. Given its wide distribution in the Southern Hemisphere, Phlegmariurus provides a good model to address questions about the biogeographical processes underlying southern distributions, notably in Madagascar and surrounding islands, also called the Western Indian Ocean (WIO). Our aims were (i) to discuss the systematics of the Malagasy species in the light of molecular phylogenetic results, (ii) to provide the first dating analysis focused on Phlegmariurus and (iii) to understand the relative role of vicariance, dispersal and diversification in the origin of the Malagasy Phlegmariurus species. The phylogenetic relationships were inferred based on three plastid DNA regions (rbcL, trnH-psbA and trnL+trnL-trnF) and on a dataset comprising 93 species, including 16 Malagasy species (80% of the total Malagasy diversity for the genus). Our results highlighted the need to combine Malagasy Huperzia species in Phlegmariurus, as well as the polyphyly of widely distributed species: Phlegmariurus phlegmaria, P. squarrosus and P. verticillatus with the Malagasy species not belonging with the types of P. phlegmaria or P. squarrosus. This led us to propose new circumscriptions of Phlegmariurus species, especially in the WIO. Our dating analysis, relying on fossil calibrations, showed that Phlegmariurus would have originated in the Late Cretaceous and diversified in the Early Eocene. The biogeographical analysis highlighted uncertainties about the biogeographical origins of Phlegmariurus: the genus would have started to diversify in an ancestral range covering at least the Neotropics and Australasia. Hypotheses on the biogeographical history of Phlegmariurus were discussed, especially the roles of long distance dispersal, migration via Antarctica and via the Boreotropics. Six long distance dispersal events over the last 40 Ma would explain the Malagasy species diversity of Phlegmariurus, in combination with an important in situ diversification starting in the Miocene.}, } @article {pmid29733500, year = {2018}, author = {Callier, V}, title = {The second biennial meeting of the Pan-American Society for Evolutionary Developmental Biology.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {3}, pages = {132-137}, doi = {10.1002/jez.b.22804}, pmid = {29733500}, issn = {1552-5015}, mesh = {Americas ; Animals ; Awards and Prizes ; *Biological Evolution ; Body Patterning ; Developmental Biology/*organization & administration ; Models, Biological ; Societies, Scientific/*organization & administration ; }, abstract = {Evodevo is concerned with understanding how phenotypes develop and evolve, how organismal diversity is generated and maintained, and how evolutionary innovations originate. The second Pan-American Society for Evolutionary Developmental Biology (PASEDB) meeting in Calgary, Canada, showcased a great variety of species and study systems, and a variety of approaches to address these questions. Although there were, like at the first PASEDB meeting, many developmental genetic and genomic studies, much of the work moved beyond comparative developmental genetics toward more integrative studies that seek explanations at different levels of the organismal hierarchy.}, } @article {pmid29733367, year = {2018}, author = {Poncin, K and Gillet, S and De Bolle, X}, title = {Learning from the master: targets and functions of the CtrA response regulator in Brucella abortus and other alpha-proteobacteria.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {500-513}, doi = {10.1093/femsre/fuy019}, pmid = {29733367}, issn = {1574-6976}, mesh = {Alphaproteobacteria/genetics/*physiology ; Bacterial Proteins/genetics/*metabolism ; Brucella abortus/genetics/*physiology ; Gene Expression Regulation, Bacterial/genetics ; Transcription Factors/genetics/*metabolism ; }, abstract = {The α-proteobacteria are a fascinating group of free-living, symbiotic and pathogenic organisms, including the Brucella genus, which is responsible for a worldwide zoonosis. One common feature of α-proteobacteria is the presence of a conserved response regulator called CtrA, first described in the model bacterium Caulobacter crescentus, where it controls gene expression at different stages of the cell cycle. Here, we focus on Brucella abortus and other intracellular α-proteobacteria in order to better assess the potential role of CtrA in the infectious context. Comparative genomic analyses of the CtrA control pathway revealed the conservation of specific modules, as well as the acquisition of new factors during evolution. The comparison of CtrA regulons also suggests that specific clades of α-proteobacteria acquired distinct functions under its control, depending on the essentiality of the transcription factor. Other CtrA-controlled functions, for instance motility and DNA repair, are proposed to be more ancestral. Altogether, these analyses provide an interesting example of the plasticity of a regulation network, subject to the constraints of inherent imperatives such as cell division and the adaptations to diversified environmental niches.}, } @article {pmid29733348, year = {2018}, author = {Rea, MA and Standish, CD and Shuster, J and Bissett, A and Reith, F}, title = {Progressive biogeochemical transformation of placer gold particles drives compositional changes in associated biofilm communities.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy080}, pmid = {29733348}, issn = {1574-6941}, abstract = {Biofilms on placer gold (Au)-particle surfaces drive Au solubilization and re-concentration thereby progressively transforming the particles. Gold solubilization induces Au-toxicity; however, Au-detoxifying community members ameliorates Au-toxicity by precipitating soluble Au to metallic Au. We hypothesize that Au-dissolution and re-concentration (precipitation) place selective pressures on associated microbial communities, leading to compositional changes and subsequent Au-particle transformation. We analyzed Au-particles from eight United Kingdom sites using next generation sequencing, electron microscopy and micro-analyses. Gold particles contained biofilms composed of prokaryotic cells and extracellular polymeric substances intermixed with (bio)minerals. Across all sites communities were dominated by Proteobacteria (689, 97% Operational Taxonomic Units, 59.3% of total reads), with β-Proteobacteria being the most abundant. A wide range of Au-morphotypes including nanoparticles, micro-crystals, sheet-like Au and secondary rims, indicated that dissolution and re-precipitation occurred, and from this transformation indices were calculated. Multivariate statistical analyses showed a significant relationship between the extent of Au-particle transformation and biofilm community composition, with putative metal-resistant Au-cycling taxa linked to progressive Au transformation. These included the genera Pseudomonas, Leptothrix and Acinetobacter. Additionally, putative exoelectrogenic genera Rhodoferax and Geobacter were highly abundant. In conclusion, biogeochemical Au-cycling and Au-particle transformation occurred at all sites and exerted a strong influence on biofilm community composition.}, } @article {pmid29733333, year = {2018}, author = {Pollet, T and Berdjeb, L and Garnier, C and Durrieu, G and Le Poupon, C and Misson, B and Jean-François, B}, title = {Prokaryotic community successions and interactions in marine biofilms: the key role of Flavobacteriia.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy083}, pmid = {29733333}, issn = {1574-6941}, abstract = {Despite clear advances in characterizing marine biofilms, details on their formation and species succession remain scarce particularly during the early stage of development. We investigated the microbial community composition and succession in coastal marine biofilms on plastic. Samples were collected over 75 days of immersion with strengthened samplings during the early stages of biofilm establishment. Biofilm composition was estimated using Illumina Miseq and microbial community interactions were assessed through microbial association network analysis. In silico analyses showed that primers used in most of previous studies considerably underestimated marine biofilm diversity. Unintentionally ignored so far, we showed that Flavobacteriia might be key actors in the functioning of marine biofilms. Gamma-proteobacteria from the genus Oleibacter strongly dominated microbial communities during the first hours of biofilm formation. These pioneer communities were quickly replaced by alpha-proteobacteria and Flavobacteriia. Bacterial communities exhibited fast temporal structure dynamics with taxa displaying rapid increases and declines. A total of 90% of operational taxonomic units (OTUs) were intermittent or ephemeral reinforcing the conclusion that marine biofilms are highly dynamics. With 2/3 of positive significant connections between bacterial OTUs, microbial biofilm communities appear to be more inclined to develop inter-specific cooperation rather than competition and might thus form sets of functional guilds with mutual metabolic exchanges.}, } @article {pmid29733121, year = {2018}, author = {Olivares, I and Karger, DN and Kessler, M}, title = {Assessing species saturation: conceptual and methodological challenges.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1874-1890}, doi = {10.1111/brv.12424}, pmid = {29733121}, issn = {1469-185X}, abstract = {Is there a maximum number of species that can coexist? Intuitively, we assume an upper limit to the number of species in a given assemblage, or that a lineage can produce, but defining and testing this limit has proven problematic. Herein, we first outline seven general challenges of studies on species saturation, most of which are independent of the actual method used to assess saturation. Among these are the challenge of defining saturation conceptually and operationally, the importance of setting an appropriate referential system, and the need to discriminate among patterns, processes and mechanisms. Second, we list and discuss the methodological approaches that have been used to study species saturation. These approaches vary in time and spatial scales, and in the variables and assumptions needed to assess saturation. We argue that assessing species saturation is possible, but that many studies conducted to date have conceptual and methodological flaws that prevent us from currently attaining a good idea of the occurrence of species saturation.}, } @article {pmid29733107, year = {2018}, author = {Sjöstedt, J and Langenheder, S and Kritzberg, E and Karlsson, CMG and Lindström, ES}, title = {Repeated disturbances affect functional but not compositional resistance and resilience in an aquatic bacterioplankton community.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {493-500}, doi = {10.1111/1758-2229.12656}, pmid = {29733107}, issn = {1758-2229}, abstract = {Disturbances are believed to be one of the main factors influencing variations in community diversity and functioning. Here we investigated if exposure to a pH press disturbance affected the composition and functional performance of a bacterial community and its resistance, recovery and resilience to a second press disturbance (salt addition). Lake bacterial assemblages were initially exposed to reduced pH in six mesocosms whereas another six mesocosms were kept as reference. Seven days after the pH disturbance, three tanks from each treatment were exposed to a salt disturbance. Both bacterial production and enzyme activity were negatively affected by the salt treatment, regardless if the communities had been subject to a previous disturbance or not. However, cell-specific enzyme activity had a higher resistance in communities pre-exposed to the pH disturbance compared to the reference treatment. In contrast, for cell-specific bacterial production resistance was not affected, but recovery was faster in the communities that had previously been exposed to the pH disturbance. Over time, bacterial community composition diverged among treatments, in response to both pH and salinity. The difference in functional recovery, resilience and resistance may depend on differences in community composition caused by the pH disturbance, niche breadth or acquired stress resistance.}, } @article {pmid29732672, year = {2018}, author = {Jetten, MSM}, title = {Fortune favours the well-read audience, authors and editors of environmental microbiology.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14127}, pmid = {29732672}, issn = {1462-2920}, } @article {pmid29732670, year = {2018}, author = {Carlson, CJ and Getz, WM and Kausrud, KL and Cizauskas, CA and Blackburn, JK and Bustos Carrillo, FA and Colwell, R and Easterday, WR and Ganz, HH and Kamath, PL and Økstad, OA and Turner, WC and Kolstø, AB and Stenseth, NC}, title = {Spores and soil from six sides: interdisciplinarity and the environmental biology of anthrax (Bacillus anthracis).}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1813-1831}, doi = {10.1111/brv.12420}, pmid = {29732670}, issn = {1469-185X}, abstract = {Environmentally transmitted diseases are comparatively poorly understood and managed, and their ecology is particularly understudied. Here we identify challenges of studying environmental transmission and persistence with a six-sided interdisciplinary review of the biology of anthrax (Bacillus anthracis). Anthrax is a zoonotic disease capable of maintaining infectious spore banks in soil for decades (or even potentially centuries), and the mechanisms of its environmental persistence have been the topic of significant research and controversy. Where anthrax is endemic, it plays an important ecological role, shaping the dynamics of entire herbivore communities. The complex eco-epidemiology of anthrax, and the mysterious biology of Bacillus anthracis during its environmental stage, have necessitated an interdisciplinary approach to pathogen research. Here, we illustrate different disciplinary perspectives through key advances made by researchers working in Etosha National Park, a long-term ecological research site in Namibia that has exemplified the complexities of the enzootic process of anthrax over decades of surveillance. In Etosha, the role of scavengers and alternative routes (waterborne transmission and flies) has proved unimportant relative to the long-term persistence of anthrax spores in soil and their infection of herbivore hosts. Carcass deposition facilitates green-ups of vegetation to attract herbivores, potentially facilitated by the role of anthrax spores in the rhizosphere. The underlying seasonal pattern of vegetation, and herbivores' immune and behavioural responses to anthrax risk, interact to produce regular 'anthrax seasons' that appear to be a stable feature of the Etosha ecosystem. Through the lens of microbiologists, geneticists, immunologists, ecologists, epidemiologists, and clinicians, we discuss how anthrax dynamics are shaped at the smallest scale by population genetics and interactions within the bacterial communities up to the broadest scales of ecosystem structure. We illustrate the benefits and challenges of this interdisciplinary approach to disease ecology, and suggest ways anthrax might offer insights into the biology of other important pathogens. Bacillus anthracis, and the more recently emerged Bacillus cereus biovar anthracis, share key features with other environmentally transmitted pathogens, including several zoonoses and panzootics of special interest for global health and conservation efforts. Understanding the dynamics of anthrax, and developing interdisciplinary research programs that explore environmental persistence, is a critical step forward for understanding these emerging threats.}, } @article {pmid29732666, year = {2018}, author = {Jiang, TX and Zhao, M and Qiu, XB}, title = {Substrate receptors of proteasomes.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1765-1777}, doi = {10.1111/brv.12419}, pmid = {29732666}, issn = {1469-185X}, support = {31530014//National Natural Science Foundation of China/International ; 91319303//National Natural Science Foundation of China/International ; 31600626//National Natural Science Foundation of China/International ; 2015NT04//Central Universities/International ; }, abstract = {Proteasomes are responsible for the turnover of most cellular proteins, and thus are critical to almost all cellular activities. A substrate entering the proteasome must first bind to a substrate receptor. Substrate receptors can be classified as ubiquitin receptors and non-ubiquitin receptors. The intrinsic ubiquitin receptors, including proteasome regulatory particle base subunits 1, 10 and 13 (Rpn1, Rpn10, and Rpn13), determine the capability of the proteasome to recognize a ubiquitin chain, and thus provide selectivity for the 26S proteasome. However, the non-ubiquitin receptors, including proteasome activator 200 (PA200) and PA28γ, have received great attention due to their remarkable compensatory roles relative to canonical ubiquitin-mediated proteasomal degradation. Herein we review recent advances in understanding the contributions of these substrate receptors to proteasomal degradation, and introduce their substrates and interacting factors. We also provide insights into their biological functions related to spermatogenesis, immune responses, cellular homeostasis, and tumour development. Finally, we summarize advances in developing small-molecule inhibitors of these substrate receptors and discuss their potential as drug targets.}, } @article {pmid29731514, year = {2018}, author = {O'Leary, BC and Ban, NC and Fernandez, M and Friedlander, AM and García-Borboroglu, P and Golbuu, Y and Guidetti, P and Harris, JM and Hawkins, JP and Langlois, T and McCauley, DJ and Pikitch, EK and Richmond, RH and Roberts, CM}, title = {Addressing Criticisms of Large-Scale Marine Protected Areas.}, journal = {Bioscience}, volume = {68}, number = {5}, pages = {359-370}, pmid = {29731514}, issn = {0006-3568}, abstract = {Designated large-scale marine protected areas (LSMPAs, 100,000 or more square kilometers) constitute over two-thirds of the approximately 6.6% of the ocean and approximately 14.5% of the exclusive economic zones within marine protected areas. Although LSMPAs have received support among scientists and conservation bodies for wilderness protection, regional ecological connectivity, and improving resilience to climate change, there are also concerns. We identified 10 common criticisms of LSMPAs along three themes: (1) placement, governance, and management; (2) political expediency; and (3) social-ecological value and cost. Through critical evaluation of scientific evidence, we discuss the value, achievements, challenges, and potential of LSMPAs in these arenas. We conclude that although some criticisms are valid and need addressing, none pertain exclusively to LSMPAs, and many involve challenges ubiquitous in management. We argue that LSMPAs are an important component of a diversified management portfolio that tempers potential losses, hedges against uncertainty, and enhances the probability of achieving sustainably managed oceans.}, } @article {pmid29731513, year = {2018}, author = {Arlidge, WNS and Bull, JW and Addison, PFE and Burgass, MJ and Gianuca, D and Gorham, TM and Jacob, C and Shumway, N and Sinclair, SP and Watson, JEM and Wilcox, C and Milner-Gulland, EJ}, title = {A Global Mitigation Hierarchy for Nature Conservation.}, journal = {Bioscience}, volume = {68}, number = {5}, pages = {336-347}, pmid = {29731513}, issn = {0006-3568}, abstract = {Efforts to conserve biodiversity comprise a patchwork of international goals, national-level plans, and local interventions that, overall, are failing. We discuss the potential utility of applying the mitigation hierarchy, widely used during economic development activities, to all negative human impacts on biodiversity. Evaluating all biodiversity losses and gains through the mitigation hierarchy could help prioritize consideration of conservation goals and drive the empirical evaluation of conservation investments through the explicit consideration of counterfactual trends and ecosystem dynamics across scales. We explore the challenges in using this framework to achieve global conservation goals, including operationalization and monitoring and compliance, and we discuss solutions and research priorities. The mitigation hierarchy's conceptual power and ability to clarify thinking could provide the step change needed to integrate the multiple elements of conservation goals and interventions in order to achieve successful biodiversity outcomes.}, } @article {pmid29731512, year = {2018}, author = {Trautmann, NM and Gilmore, MP}, title = {Educating as if Survival Matters.}, journal = {Bioscience}, volume = {68}, number = {5}, pages = {324-326}, doi = {10.1093/biosci/biy026}, pmid = {29731512}, issn = {0006-3568}, } @article {pmid29731449, year = {2018}, author = {Pattie, RW and Callahan, NB and Cude-Woods, C and Adamek, ER and Broussard, LJ and Clayton, SM and Currie, SA and Dees, EB and Ding, X and Engel, EM and Fellers, DE and Fox, W and Geltenbort, P and Hickerson, KP and Hoffbauer, MA and Holley, AT and Komives, A and Liu, CY and MacDonald, SWT and Makela, M and Morris, CL and Ortiz, JD and Ramsey, J and Salvat, DJ and Saunders, A and Seestrom, SJ and Sharapov, EI and Sjue, SK and Tang, Z and Vanderwerp, J and Vogelaar, B and Walstrom, PL and Wang, Z and Wei, W and Weaver, HL and Wexler, JW and Womack, TL and Young, AR and Zeck, BA}, title = {Measurement of the neutron lifetime using a magneto-gravitational trap and in situ detection.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {627-632}, doi = {10.1126/science.aan8895}, pmid = {29731449}, issn = {1095-9203}, abstract = {The precise value of the mean neutron lifetime, τn, plays an important role in nuclear and particle physics and cosmology. It is used to predict the ratio of protons to helium atoms in the primordial universe and to search for physics beyond the Standard Model of particle physics. We eliminated loss mechanisms present in previous trap experiments by levitating polarized ultracold neutrons above the surface of an asymmetric storage trap using a repulsive magnetic field gradient so that the stored neutrons do not interact with material trap walls. As a result of this approach and the use of an in situ neutron detector, the lifetime reported here [877.7 ± 0.7 (stat) +0.4/-0.2 (sys) seconds] does not require corrections larger than the quoted uncertainties.}, } @article {pmid29731376, year = {2018}, author = {Dou, Y and Gold, HD and Luquette, LJ and Park, PJ}, title = {Detecting Somatic Mutations in Normal Cells.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {7}, pages = {545-557}, pmid = {29731376}, issn = {0168-9525}, support = {R01 NS032457/NS/NINDS NIH HHS/United States ; U01 MH106883/MH/NIMH NIH HHS/United States ; U01 MH106891/MH/NIMH NIH HHS/United States ; }, abstract = {Somatic mutations have been studied extensively in the context of cancer. Recent studies have demonstrated that high-throughput sequencing data can be used to detect somatic mutations in non-tumor cells. Analysis of such mutations allows us to better understand the mutational processes in normal cells, explore cell lineages in development, and examine potential associations with age-related disease. We describe here approaches for characterizing somatic mutations in normal and non-tumor disease tissues. We discuss several experimental designs and common pitfalls in somatic mutation detection, as well as more recent developments such as phasing and linked-read technology. With the dramatically increasing numbers of samples undergoing genome sequencing, bioinformatic analysis will enable the characterization of somatic mutations and their impact on non-cancer tissues.}, } @article {pmid29731154, year = {2018}, author = {Wellenreuther, M and Bernatchez, L}, title = {Eco-Evolutionary Genomics of Chromosomal Inversions.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {427-440}, doi = {10.1016/j.tree.2018.04.002}, pmid = {29731154}, issn = {1872-8383}, mesh = {Chromosome Inversion/*genetics ; *Evolution, Molecular ; Genomics ; Models, Genetic ; *Polymorphism, Genetic ; }, abstract = {Chromosomal inversions have long fascinated evolutionary biologists due to their suppression of recombination, which can protect co-adapted alleles. Emerging research documents that inversions are commonly linked to spectacular phenotypes and have a pervasive role in eco-evolutionary processes, from mating systems, social organisation, environmental adaptation, and reproductive isolation to speciation. Studies also reveal that inversions are taxonomically widespread, with many being old and large, and that balancing selection is commonly facilitating their maintenance. This challenges the traditional view that the role of balancing selection in maintaining variation is relatively minor. The ubiquitous importance of inversions in ecological and evolutionary processes suggests that structural variation should be better acknowledged and integrated in studies pertaining to the molecular basis of adaptation and speciation.}, } @article {pmid29731153, year = {2018}, author = {Gounand, I and Harvey, E and Little, CJ and Altermatt, F}, title = {On Embedding Meta-ecosystems into a Socioecological Framework: A Reply to Renaud et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {484-486}, doi = {10.1016/j.tree.2018.04.004}, pmid = {29731153}, issn = {1872-8383}, } @article {pmid29731152, year = {2018}, author = {Renaud, PC and de O Roque, F and Souza, FL and Pays, O and Laurent, F and Fritz, H and Fischer, E and Fabricius, C}, title = {Towards a Meta-Social-Ecological System Perspective: A Response to Gounand et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {481-482}, doi = {10.1016/j.tree.2018.04.005}, pmid = {29731152}, issn = {1872-8383}, } @article {pmid29731151, year = {2018}, author = {Emerson, BC and Patiño, J}, title = {Anagenesis, Cladogenesis, and Speciation on Islands.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {488-491}, doi = {10.1016/j.tree.2018.04.006}, pmid = {29731151}, issn = {1872-8383}, abstract = {Anagenesis and cladogenesis are fundamental evolutionary concepts, but are increasingly being adopted as speciation models in the field of island biogeography. Here, we review the origin of the terms 'anagenetic' and 'cladogenetic' speciation, critique their utility, and finally suggest alternative terminology that better describes the geographical relationships of insular sister species.}, } @article {pmid29730990, year = {2018}, author = {Schmidt, A and Marabita, F and Kiani, NA and Gross, CC and Johansson, HJ and Éliás, S and Rautio, S and Eriksson, M and Fernandes, SJ and Silberberg, G and Ullah, U and Bhatia, U and Lähdesmäki, H and Lehtiö, J and Gomez-Cabrero, D and Wiendl, H and Lahesmaa, R and Tegnér, J}, title = {Time-resolved transcriptome and proteome landscape of human regulatory T cell (Treg) differentiation reveals novel regulators of FOXP3.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {47}, pmid = {29730990}, issn = {1741-7007}, abstract = {BACKGROUND: Regulatory T cells (Tregs) expressing the transcription factor FOXP3 are crucial mediators of self-tolerance, preventing autoimmune diseases but possibly hampering tumor rejection. Clinical manipulation of Tregs is of great interest, and first-in-man trials of Treg transfer have achieved promising outcomes. Yet, the mechanisms governing induced Treg (iTreg) differentiation and the regulation of FOXP3 are incompletely understood.

RESULTS: To gain a comprehensive and unbiased molecular understanding of FOXP3 induction, we performed time-series RNA sequencing (RNA-Seq) and proteomics profiling on the same samples during human iTreg differentiation. To enable the broad analysis of universal FOXP3-inducing pathways, we used five differentiation protocols in parallel. Integrative analysis of the transcriptome and proteome confirmed involvement of specific molecular processes, as well as overlap of a novel iTreg subnetwork with known Treg regulators and autoimmunity-associated genes. Importantly, we propose 37 novel molecules putatively involved in iTreg differentiation. Their relevance was validated by a targeted shRNA screen confirming a functional role in FOXP3 induction, discriminant analyses classifying iTregs accordingly, and comparable expression in an independent novel iTreg RNA-Seq dataset.

CONCLUSION: The data generated by this novel approach facilitates understanding of the molecular mechanisms underlying iTreg generation as well as of the concomitant changes in the transcriptome and proteome. Our results provide a reference map exploitable for future discovery of markers and drug candidates governing control of Tregs, which has important implications for the treatment of cancer, autoimmune, and inflammatory diseases.}, } @article {pmid29730674, year = {2018}, author = {Wichmann, T}, title = {Models of Parkinson's disease revisited.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {169-170}, doi = {10.1038/d41586-018-02589-8}, pmid = {29730674}, issn = {1476-4687}, support = {P50 NS098685/NS/NINDS NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; R01 NS083386/NS/NINDS NIH HHS/United States ; }, mesh = {Humans ; *Parkinson Disease ; }, } @article {pmid29730673, year = {2018}, author = {Lin, D}, title = {Connections that control defence strategy.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {172-174}, doi = {10.1038/d41586-018-04747-4}, pmid = {29730673}, issn = {1476-4687}, mesh = {Animals ; Fear ; Thalamus/*physiology ; *Visual Perception ; }, } @article {pmid29730672, year = {2018}, author = {Kocak, DD and Gersbach, CA}, title = {From CRISPR scissors to virus sensors.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {168-169}, doi = {10.1038/d41586-018-04975-8}, pmid = {29730672}, issn = {1476-4687}, mesh = {CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; DNA Viruses ; *Gene Editing ; }, } @article {pmid29730671, year = {2018}, author = {Stone, MD}, title = {Detailed view of human telomerase enzyme invites rethink of its structure.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {174-175}, doi = {10.1038/d41586-018-04756-3}, pmid = {29730671}, issn = {1476-4687}, mesh = {Humans ; Nucleic Acid Conformation ; RNA ; Telomerase/*genetics ; *Telomere ; }, } @article {pmid29729933, year = {2018}, author = {Lopes-Lima, M and Bolotov, IN and Do, VT and Aldridge, DC and Fonseca, MM and Gan, HM and Gofarov, MY and Kondakov, AV and Prié, V and Sousa, R and Varandas, S and Vikhrev, IV and Teixeira, A and Wu, RW and Wu, X and Zieritz, A and Froufe, E and Bogan, AE}, title = {Expansion and systematics redefinition of the most threatened freshwater mussel family, the Margaritiferidae.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {98-118}, doi = {10.1016/j.ympev.2018.04.041}, pmid = {29729933}, issn = {1095-9513}, abstract = {Two Unionida (freshwater mussel) families are present in the Northern Hemisphere; the Margaritiferidae, representing the most threatened of unionid families, and the Unionidae, which include several genera of unresolved taxonomic placement. The recent reassignment of the poorly studied Lamprotula rochechouartii from the Unionidae to the Margaritiferidae motivated a new search for other potential species of margaritiferids from members of Gibbosula and Lamprotula. Based on molecular and morphological analyses conducted on newly collected specimens from Vietnam, we here assign Gibbosula crassa to the Margaritiferidae. Additionally, we reanalyzed all diagnostic characteristics of the Margaritiferidae and examined museum specimens of Lamprotula and Gibbosula. As a result, two additional species are also moved to the Margaritiferidae, i.e. Gibbosula confragosa and Gibbosula polysticta. We performed a robust five marker phylogeny with all available margaritiferid species and discuss the taxonomy within the family. The present phylogeny reveals the division of Margaritiferidae into four ancient clades with distinct morphological, biogeographical and ecological characteristics that justify the division of the Margaritiferidae into two subfamilies (Gibbosulinae and Margaritiferinae) and four genera (Gibbosula, Cumberlandia, Margaritifera, and Pseudunio). The systematics of the Margaritiferidae family is re-defined as well as their distribution, potential origin and main biogeographic patterns.}, } @article {pmid29729671, year = {2018}, author = {Trosvik, P and de Muinck, EJ and Rueness, EK and Fashing, PJ and Beierschmitt, EC and Callingham, KR and Kraus, JB and Trew, TH and Moges, A and Mekonnen, A and Venkataraman, VV and Nguyen, N}, title = {Multilevel social structure and diet shape the gut microbiota of the gelada monkey, the only grazing primate.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {84}, pmid = {29729671}, issn = {2049-2618}, support = {230796/F20//Norges Forskningsråd/International ; 11727-1//Rufford Foundation/International ; }, mesh = {Animals ; Bacteria/*classification/*isolation & purification ; Base Sequence ; Diet ; Digestion/physiology ; Ethiopia ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/anatomy & histology/*microbiology ; Rumen/*microbiology ; Sequence Analysis, DNA ; Sheep/*microbiology ; Theropithecus/*microbiology ; }, abstract = {BACKGROUND: The gelada monkey (Theropithecus gelada), endemic to the Ethiopian highlands, is the only graminivorous primate, i.e., it feeds mainly on grasses and sedges. In spite of known dental, manual, and locomotor adaptations, the intestinal anatomy of geladas is similar to that of other primates. We currently lack a clear understanding of the adaptations in digestive physiology necessary for this species to subsist on a graminoid-based diet, but digestion in other graminivores, such as ruminants, relies heavily on the microbial community residing in the gastrointestinal (GI) system. Furthermore, geladas form complex, multilevel societies, making them a suitable system for investigating links between sociality and the GI microbiota.

RESULTS: Here, we explore the gastrointestinal microbiota of gelada monkeys inhabiting an intact ecosystem and document how factors like multilevel social structure and seasonal changes in diet shape the GI microbiota. We compare the gelada GI microbiota to those of other primate species, reporting a gradient from geladas to herbivorous specialist monkeys to dietary generalist monkeys and lastly humans, the ultimate ecological generalists. We also compare the microbiotas of the gelada GI tract and the sheep rumen, finding that geladas are highly enriched for cellulolytic bacteria associated with ruminant digestion, relative to other primates.

CONCLUSIONS: This study represents the first analysis of the gelada GI microbiota, providing insights into the adaptations underlying graminivory in a primate. Our results also highlight the role of social organization in structuring the GI microbiota within a society of wild animals.}, } @article {pmid29729663, year = {2018}, author = {Deutscher, AT and Burke, CM and Darling, AE and Riegler, M and Reynolds, OL and Chapman, TA}, title = {Near full-length 16S rRNA gene next-generation sequencing revealed Asaia as a common midgut bacterium of wild and domesticated Queensland fruit fly larvae.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {85}, pmid = {29729663}, issn = {2049-2618}, support = {Olivia L Reynolds//Horticulture Australia/International ; }, mesh = {*Acetobacteraceae/classification/genetics/isolation & purification ; Animals ; Gastrointestinal Microbiome/*genetics ; Genome/genetics ; High-Throughput Nucleotide Sequencing ; Larva/microbiology ; RNA, Ribosomal, 16S/*genetics ; Symbiosis/physiology ; Tephritidae/*microbiology ; }, abstract = {BACKGROUND: Gut microbiota affects tephritid (Diptera: Tephritidae) fruit fly development, physiology, behavior, and thus the quality of flies mass-reared for the sterile insect technique (SIT), a target-specific, sustainable, environmentally benign form of pest management. The Queensland fruit fly, Bactrocera tryoni (Tephritidae), is a significant horticultural pest in Australia and can be managed with SIT. Little is known about the impacts that laboratory-adaptation (domestication) and mass-rearing have on the tephritid larval gut microbiome. Read lengths of previous fruit fly next-generation sequencing (NGS) studies have limited the resolution of microbiome studies, and the diversity within populations is often overlooked. In this study, we used a new near full-length (> 1300 nt) 16S rRNA gene amplicon NGS approach to characterize gut bacterial communities of individual B. tryoni larvae from two field populations (developing in peaches) and three domesticated populations (mass- or laboratory-reared on artificial diets).

RESULTS: Near full-length 16S rRNA gene sequences were obtained for 56 B. tryoni larvae. OTU clustering at 99% similarity revealed that gut bacterial diversity was low and significantly lower in domesticated larvae. Bacteria commonly associated with fruit (Acetobacteraceae, Enterobacteriaceae, and Leuconostocaceae) were detected in wild larvae, but were largely absent from domesticated larvae. However, Asaia, an acetic acid bacterium not frequently detected within adult tephritid species, was detected in larvae of both wild and domesticated populations (55 out of 56 larval gut samples). Larvae from the same single peach shared a similar gut bacterial profile, whereas larvae from different peaches collected from the same tree had different gut bacterial profiles. Clustering of the Asaia near full-length sequences at 100% similarity showed that the wild flies from different locations had different Asaia strains.

CONCLUSIONS: Variation in the gut bacterial communities of B. tryoni larvae depends on diet, domestication, and horizontal acquisition. Bacterial variation in wild larvae suggests that more than one bacterial species can perform the same functional role; however, Asaia could be an important gut bacterium in larvae and warrants further study. A greater understanding of the functions of the bacteria detected in larvae could lead to increased fly quality and performance as part of the SIT.}, } @article {pmid29729259, year = {2018}, author = {Armstrong, AR and Drummond-Barbosa, D}, title = {Insulin signaling acts in adult adipocytes via GSK-3β and independently of FOXO to control Drosophila female germline stem cell numbers.}, journal = {Developmental biology}, volume = {440}, number = {1}, pages = {31-39}, pmid = {29729259}, issn = {1095-564X}, support = {F32 GM106718/GM/NIGMS NIH HHS/United States ; R01 GM069875/GM/NIGMS NIH HHS/United States ; T32 CA009110/CA/NCI NIH HHS/United States ; }, mesh = {Adipocytes/metabolism/*physiology ; Adult Germline Stem Cells/metabolism/*physiology ; Animals ; Cell Count ; Cell Proliferation ; Drosophila/metabolism ; Drosophila Proteins/metabolism/physiology ; Female ; Forkhead Transcription Factors/metabolism/physiology ; Germ Cells/cytology ; Glycogen Synthase Kinase 3 beta/*metabolism/physiology ; Insulin/metabolism ; Male ; Oogenesis/physiology ; Ovary/cytology ; Proto-Oncogene Proteins c-akt/metabolism ; Signal Transduction/physiology ; Stem Cells/cytology ; }, abstract = {Tissue-specific stem cells are tied to the nutritional and physiological environment of adult organisms. Adipocytes have key endocrine and nutrient-sensing roles and have emerged as major players in relaying dietary information to regulate other organs. For example, previous studies in Drosophila melanogaster revealed that amino acid sensing as well as diet-dependent metabolic pathways function in adipocytes to influence the maintenance of female germline stem cells (GSCs). How nutrient-sensing pathways acting within adipocytes influence adult stem cell lineages, however, is just beginning to be elucidated. Here, we report that insulin/insulin-like growth factor signaling in adipocytes promotes GSC maintenance, early germline cyst survival, and vitellogenesis. Further, adipocytes use distinct mechanisms downstream of insulin receptor activation to control these aspects of oogenesis, all of which are independent of FOXO. We find that GSC maintenance is modulated by Akt1 through GSK-3β, early germline cyst survival is downstream of adipocyte Akt1 but independent of GSK-3β, and vitellogenesis is regulated through an Akt1-independent pathway in adipocytes. These results indicate that, in addition to employing different types of nutrient sensing, adipocytes can use distinct axes of a single nutrient-sensing pathway to regulate multiple stages of the GSC lineage in the ovary.}, } @article {pmid29728762, year = {2018}, author = {Walczyńska, A and Labecka, AM and Sobczyk, M}, title = {What may a fussy creature reveal about body/cell size integration under stressful conditions?.}, journal = {Development genes and evolution}, volume = {228}, number = {3-4}, pages = {179-188}, pmid = {29728762}, issn = {1432-041X}, support = {POMOST/2011-3/12//Foundation for Polish Science/International ; DS/INoŚ/757/2017//Uniwersytet Jagielloński/International ; }, mesh = {Animals ; Annelida/*growth & development/*physiology ; Biological Evolution ; *Body Size ; *Cell Size ; Phenotype ; Stress, Physiological ; Temperature ; }, abstract = {There is a growing amount of empirical evidence on the important role of cell size in body size adjustment in ambient or changing conditions. Though the adaptive significance of their correspondence is well understood and demonstrated, the proximate mechanisms are still in a phase of speculation. We made interesting observations on body/cell size adjustment under stressful conditions during an experiment designed for another purpose. We found that the strength of the body/cell size match is condition-dependent. Specifically, it is stronger under more stressful conditions, and it changes depending on exposure to lower temperature vs. exposure to higher temperature. The question whether these observations are of limiting or adaptive character remains open; yet, according to our results, both versions are possible but may differ in response to stress caused by too low vs. too high temperatures. Our results suggest that testing the hypotheses on body/cell size match may be a promising study system for the recent scientific dispute on the evolutionary meaning of developmental noise as opposed to phenotypic plasticity.}, } @article {pmid29728687, year = {2018}, author = {}, title = {Human hand electrified with 3D printer.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {142-143}, doi = {10.1038/d41586-018-05019-x}, pmid = {29728687}, issn = {1476-4687}, } @article {pmid29728686, year = {2018}, author = {}, title = {Grey hair may have roots in immune system.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {143}, doi = {10.1038/d41586-018-05053-9}, pmid = {29728686}, issn = {1476-4687}, } @article {pmid29728685, year = {2018}, author = {}, title = {Recipe revealed for a plant-based anti-cancer drug.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {143}, doi = {10.1038/d41586-018-05106-z}, pmid = {29728685}, issn = {1476-4687}, } @article {pmid29728684, year = {2018}, author = {}, title = {Tissue-thin lasers flex to hug curves.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {143}, doi = {10.1038/d41586-018-05032-0}, pmid = {29728684}, issn = {1476-4687}, } @article {pmid29728683, year = {2018}, author = {}, title = {Fault reversal a harbinger of large quakes.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {142}, doi = {10.1038/d41586-018-05051-x}, pmid = {29728683}, issn = {1476-4687}, } @article {pmid29728682, year = {2018}, author = {}, title = {Bats forgo sonar to fly under the radar.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {142}, doi = {10.1038/d41586-018-05033-z}, pmid = {29728682}, issn = {1476-4687}, } @article {pmid29728681, year = {2018}, author = {}, title = {Feeble flu vaccine still wields power.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {143}, doi = {10.1038/d41586-018-05020-4}, pmid = {29728681}, issn = {1476-4687}, } @article {pmid29728680, year = {2018}, author = {}, title = {DNA uncovers the source of a rose's bloom.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {142}, doi = {10.1038/d41586-018-05021-3}, pmid = {29728680}, issn = {1476-4687}, } @article {pmid29728679, year = {2018}, author = {}, title = {Whale shark makes record-setting swim.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {143}, doi = {10.1038/d41586-018-05018-y}, pmid = {29728679}, issn = {1476-4687}, } @article {pmid29728465, year = {2018}, author = {de Azevedo, S and González, MF and Cintas, C and Ramallo, V and Quinto-Sánchez, M and Márquez, F and Hünemeier, T and Paschetta, C and Ruderman, A and Navarro, P and Pazos, BA and Silva de Cerqueira, CC and Velan, O and Ramírez-Rozzi, F and Calvo, N and Castro, HG and Paz, RR and González-José, R}, title = {Reply to Evteev and Heuzé: How to overcome the problem of modeling respiration departing from bony structures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4739-E4740}, pmid = {29728465}, issn = {1091-6490}, mesh = {*Bone and Bones ; *Respiration ; }, } @article {pmid29728464, year = {2018}, author = {Norman, MR and Davis, JCS}, title = {Quantum oscillations in a biaxial pair density wave state.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5389-5391}, pmid = {29728464}, issn = {1091-6490}, abstract = {There has been growing speculation that a pair density wave state is a key component of the phenomenology of the pseudogap phase in the cuprates. Recently, direct evidence for such a state has emerged from an analysis of scanning tunneling microscopy data in halos around the vortex cores. By extrapolation, these vortex halos would then overlap at a magnetic-field scale where quantum oscillations have been observed. Here, we show that a biaxial pair density wave state gives a unique description of the quantum oscillation data, bolstering the case that the pseudogap phase in the cuprates may be a pair density wave state.}, } @article {pmid29728463, year = {2018}, author = {Caprariello, AV and Rogers, JA and Morgan, ML and Hoghooghi, V and Plemel, JR and Koebel, A and Tsutsui, S and Dunn, JF and Kotra, LP and Ousman, SS and Wee Yong, V and Stys, PK}, title = {Biochemically altered myelin triggers autoimmune demyelination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5528-5533}, pmid = {29728463}, issn = {1091-6490}, support = {MOP126040//CIHR/Canada ; PPP136719//CIHR/Canada ; }, mesh = {Animals ; Cuprizone/toxicity ; Demyelinating Diseases/*etiology/pathology ; *Disease Models, Animal ; Encephalitis/chemically induced/immunology/*pathology ; Hashimoto Disease/chemically induced/immunology/*pathology ; Humans ; Hydrolases/genetics/metabolism ; Inflammation/chemically induced/immunology/*pathology ; Male ; Mice ; Mice, Inbred C57BL ; Monoamine Oxidase Inhibitors/toxicity ; Multiple Sclerosis/*etiology/pathology ; Myelin Sheath/immunology/metabolism/*pathology ; }, abstract = {Although immune attack against central nervous system (CNS) myelin is a central feature of multiple sclerosis (MS), its root cause is unresolved. In this report, we provide direct evidence that subtle biochemical modifications to brain myelin elicit pathological immune responses with radiological and histological properties similar to MS lesions. A subtle myelinopathy induced by abbreviated cuprizone treatment, coupled with subsequent immune stimulation, resulted in lesions of inflammatory demyelination. The degree of myelin injury dictated the resulting immune response; biochemical damage that was too limited or too extensive failed to trigger overt pathology. An inhibitor of peptidyl arginine deiminases (PADs), enzymes that alter myelin structure and correlate with MS lesion severity, mitigated pathology even when administered only during the myelin-altering phase. Moreover, cultured splenocytes were reactive against donor myelin isolates, a response that was substantially muted when splenocytes were exposed to myelin from donors treated with PAD inhibitors. By showing that a primary biochemical myelinopathy can trigger secondary pathological inflammation, "cuprizone autoimmune encephalitis" potentially reconciles conflicting theories about MS pathogenesis and provides a strong rationale for investigating myelin as a primary target for early, preventative therapy.}, } @article {pmid29728462, year = {2018}, author = {Belliveau, NM and Barnes, SL and Ireland, WT and Jones, DL and Sweredoski, MJ and Moradian, A and Hess, S and Kinney, JB and Phillips, R}, title = {Systematic approach for dissecting the molecular mechanisms of transcriptional regulation in bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4796-E4805}, pmid = {29728462}, issn = {1091-6490}, support = {DP1 OD000217/OD/NIH HHS/United States ; R01 GM085286/GM/NIGMS NIH HHS/United States ; R35 GM118043/GM/NIGMS NIH HHS/United States ; S10 RR029594/RR/NCRR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Escherichia coli/*genetics/growth & development/metabolism ; Escherichia coli Proteins/genetics/*metabolism ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Green Fluorescent Proteins/*metabolism ; *Promoter Regions, Genetic ; Transcriptional Activation ; }, abstract = {Gene regulation is one of the most ubiquitous processes in biology. However, while the catalog of bacterial genomes continues to expand rapidly, we remain ignorant about how almost all of the genes in these genomes are regulated. At present, characterizing the molecular mechanisms by which individual regulatory sequences operate requires focused efforts using low-throughput methods. Here, we take a first step toward multipromoter dissection and show how a combination of massively parallel reporter assays, mass spectrometry, and information-theoretic modeling can be used to dissect multiple bacterial promoters in a systematic way. We show this approach on both well-studied and previously uncharacterized promoters in the enteric bacterium Escherichia coli In all cases, we recover nucleotide-resolution models of promoter mechanism. For some promoters, including previously unannotated ones, the approach allowed us to further extract quantitative biophysical models describing input-output relationships. Given the generality of the approach presented here, it opens up the possibility of quantitatively dissecting the mechanisms of promoter function in E. coli and a wide range of other bacteria.}, } @article {pmid29728461, year = {2018}, author = {Evteev, AA and Heuzé, Y}, title = {Impact of sampling strategies and reconstruction protocols in nasal airflow simulations in fossil hominins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4737-E4738}, pmid = {29728461}, issn = {1091-6490}, mesh = {Animals ; Computer Simulation ; *Fossils ; *Hominidae ; }, } @article {pmid29728139, year = {2018}, author = {Onyiah, P and Adamu, AY and Afolabi, RF and Ajumobi, O and Ughasoro, MD and Odeyinka, O and Nguku, P and Ajayi, IO}, title = {Bottlenecks, concerns and needs in malaria operational research: the perspectives of key stakeholders in Nigeria.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {272}, pmid = {29728139}, issn = {1756-0500}, support = {GH15-1619) U2GGH001876//Centers for Disease Control and Prevention/ ; }, mesh = {Adult ; Cross-Sectional Studies ; Female ; Health Personnel ; Humans ; *Malaria/epidemiology/prevention & control ; Male ; Middle Aged ; Nigeria ; *Operations Research ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: We conducted a study to determine stakeholders' perspective of the bottlenecks, concerns and needs to malaria operational research (MOR) agenda setting in Nigeria.

RESULTS: Eighty-five (37.9%) stakeholders identified lack of positive behavioural change as the major bottleneck to MOR across the malaria thematic areas comprising of malaria prevention 58.8% (50), case management 34.8% (39), advocacy communication and social mobilisation 4.7% (4) while procurement and supply chain management (PSM) and programme management experts had the least response of 1.2% (1) each. Other bottlenecks were inadequate capacity to implement (13.8%, n = 31), inadequate funds (11.6%, n = 26), poor supply management (9.4%, n = 21), administrative bureaucracy (5.8%, n = 13), inadequacy of experts (1.3%, n = 3) and poor policy implementation (4.9%, n = 11). Of the 31 stakeholders who opined lack of capacity to execute malaria operational research; 17 (54.8%), 10 (32.3%), 3 (9.7%) and 1 (3.2%) were experts in case management, malaria prevention, surveillance, monitoring and evaluation and PSM respectively. Improvement in community enlightenment and awareness strategies; and active involvement of health care workers public and private sectors were identified solutions to lack of positive behavioural change.}, } @article {pmid29728138, year = {2018}, author = {Francesconi, W and Berton, F and Marcondes, MCG}, title = {HIV-1 Tat alters neuronal intrinsic excitability.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {275}, pmid = {29728138}, issn = {1756-0500}, support = {P30 AI036214/AI/NIAID NIH HHS/United States ; R01DA036164//National Institute on Drug Abuse/ ; }, mesh = {Animals ; HIV-1/*metabolism ; *Hippocampus/drug effects ; *Membrane Potentials/drug effects ; Mice ; Mice, Inbred C57BL ; *Pyramidal Cells/drug effects ; Recombinant Proteins ; *Synaptic Transmission/drug effects ; tat Gene Products, Human Immunodeficiency Virus/*pharmacology ; }, abstract = {OBJECTIVE: In HIV+ individuals, the virus enters the central nervous system and invades innate immune cells, producing important changes that result in neurological deficits. We aimed to determine whether HIV plays a direct role in neuronal excitability. Of the HIV peptides, Tat is secreted and acts in other cells. In order to examine whether the HIV Tat can modify neuronal excitability, we exposed primary murine hippocampal neurons to that peptide, and tested its effects on the intrinsic membrane properties, 4 and 24 h after exposure.

RESULTS: The exposure of hippocampal pyramidal neurons to Tat for 4 h did not alter intrinsic membrane properties. However, we found a strong increase in intrinsic excitability, characterized by increase of the slope (Gain) of the input-output function, in cells treated with Tat for 24 h. Nevertheless, Tat treatment for 24 h did not alter the resting membrane potential, input resistance, rheobase and action potential threshold. Thus, neuronal adaptability to Tat exposure for 24 h is not applicable to basic neuronal properties. A restricted but significant effect on coupling the inputs to the outputs may have implications to our knowledge of Tat biophysical firing capability, and its involvement in neuronal hyperexcitability in neuroHIV.}, } @article {pmid29728136, year = {2018}, author = {Mengist, HM and Demeke, G and Zewdie, O and Belew, A}, title = {Diagnostic performance of direct wet mount microscopy in detecting intestinal helminths among pregnant women attending ante-natal care (ANC) in East Wollega, Oromia, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {276}, pmid = {29728136}, issn = {1756-0500}, mesh = {Adult ; Animals ; Clinical Laboratory Techniques/*standards ; Cross-Sectional Studies ; Ethiopia ; Feces/*parasitology ; Female ; Helminthiasis/*diagnosis ; *Helminths ; Humans ; Intestinal Diseases, Parasitic/*diagnosis ; Pregnancy ; Pregnancy Complications, Parasitic/*diagnosis ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: The aim of this study was to evaluate the diagnostic performance of direct wet mount microscopy compared to formalin ether concentration (FEC) technique in detecting intestinal helminths in pregnant women.

RESULTS: The total prevalence of intestinal helminths was 18.8% (70/372) by direct wet mount microscopy and 24.7% (92/372) by FEC technique (P < 0.001). The sensitivity, negative predictive value (NPV) and test efficiency (TE) of direct wet mount microscopy in diagnosing intestinal helminths was 76, 92.7 and 94%, respectively. The sensitivity of direct w et mount microscopy was very low in detecting ova of Hymenolepis nana. The two methods showed excellent agreement in detecting ova of Hook worm and Ascaris lumbricoides (Kappa > 0.81) but they fairly agreed in detecting ova of Hymenolepis nana (Kappa = 0.39). Intestinal helminths were underdiagnosed and the total diagnostic performance of direct wet mount microscopy was significantly poor in detecting intestinal helminths as compared to FEC technique. Routine use of FEC method is recommended for the diagnosis of intestinal helminths in pregnant women.}, } @article {pmid29728133, year = {2018}, author = {Muth, DC and Powell, BH and Zhao, Z and Witwer, KW}, title = {miRNAs in platelet-poor blood plasma and purified RNA are highly stable: a confirmatory study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {273}, pmid = {29728133}, issn = {1756-0500}, support = {Catalyst Award//Johns Hopkins University/ ; P30AI094189//National Institutes of Health (US)/ ; R56 AG057430/AG/NIA NIH HHS/United States ; R01 DA040385/DA/NIDA NIH HHS/United States ; OD011089//National Institutes of Health (US)/ ; T32 GM008752/GM/NIGMS NIH HHS/United States ; DA040385//National Institute on Drug Abuse (US)/ ; }, mesh = {*Argonaute Proteins ; Biomarkers/blood ; *Blood Platelets ; Freezing ; Humans ; MicroRNAs/*blood ; *Plasma ; Polymerase Chain Reaction ; *Preservation, Biological ; *RNA Stability ; *Tissue Preservation ; }, abstract = {OBJECTIVE: We wished to re-assess the relative stability of microRNAs (miRNAs) as compared with other RNA molecules, which has been confirmed in many contexts. When bound to Argonaute proteins, miRNAs are protected from degradation, even when released into the extracellular space in ribonucleoprotein complexes, and with or without the protection of membranes in extracellular vesicles. Purified miRNAs also appear to present less of a target for degradation than other RNAs. Although miRNAs are by no means immune to degradation, biological samples subjected to prolonged incubation at room temperature, multiple freeze/thaws, or collection in the presence of inhibitors like heparin, can typically be remediated or used directly for miRNA measurements.

RESULTS: Here, we provide additional confirmation of early, well validated findings on miRNA stability and detectability. Our data also suggest that inadequate depletion of platelets from plasma may explain the occasional report that freeze-thaw cycles can adversely affect plasma miRNA levels. Overall, the repeated observation of miRNA stability is again confirmed.}, } @article {pmid29728132, year = {2018}, author = {Gardeshi, Z and Amini, M and Nabeiei, P}, title = {The perception of hidden curriculum among undergraduate medical students: a qualitative study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {271}, pmid = {29728132}, issn = {1756-0500}, mesh = {Adult ; *Curriculum ; Education, Medical, Undergraduate/*methods ; Female ; Humans ; Male ; Qualitative Research ; *Students, Medical/psychology ; Young Adult ; }, abstract = {OBJECTIVES: The effect of hidden curriculum on student learning has not been sufficiently recognized in most of the revised curriculums. This study is a qualitative study that measures the students' perception of hidden curriculum through semi-structured interviews. All of the interviews were recorded and then converted into scripts. These scripts were divided to sentences and phrases and named as units. Units aggregated with similar groups and named as codes, then the similar codes were aggregated into themes.

RESULTS: Four main themes emerged, role modeling, personal attitude and beliefs, hierarchy, social and ethical culture. The results of the present study showed that it is necessary to discuss the hidden curriculum. We are unaware of the hidden curriculum, but even when were are aware of it, we are unwilling to act. Information about issues related to the hidden and informal curriculum, as well as knowing the viewpoints of students is necessary. It seems necessary to provide data to students about the hidden curriculum and encouraging patient centered curriculums early in training, such as integrated curriculum.}, } @article {pmid29728126, year = {2018}, author = {Wickramasinghe, ND and Dissanayake, DS and Abeywardena, GS}, title = {Validity and reliability of the Utrecht Work Engagement Scale-Student Version in Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {277}, pmid = {29728126}, issn = {1756-0500}, support = {UGC/DRIC/PG/2015(I)/RUSL/01//University Grants Commission-Sri Lanka/ ; }, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; Psychometrics/*instrumentation/*methods/*standards ; Reproducibility of Results ; Sri Lanka ; Students/*psychology ; Universities ; *Work Engagement ; Young Adult ; }, abstract = {OBJECTIVE: The present study was aimed at assessing the validity and the reliability of the Sinhala version of the Utrecht Work Engagement Scale-Student Version (UWES-S) among collegiate cycle students in Sri Lanka.

RESULTS: The 17-item UWES-S was translated to Sinhala and the judgmental validity was assessed by a multi-disciplinary panel of experts. Construct validity of the UWES-S was appraised by using multi-trait scaling analysis and exploratory factor analysis (EFA) on data obtained from a sample of 194 grade thirteen students in the Kurunegala district, Sri Lanka. Reliability of the UWES-S was assessed by using internal consistency and test-retest reliability. Except for item 13, all other items showed good psychometric properties in judgemental validity, item-convergent validity and item-discriminant validity. EFA using principal component analysis with Oblimin rotation, suggested a three-factor solution (including vigor, dedication and absorption subscales) explaining 65.4% of the total variance for the 16-item UWES-S (with item 13 deleted). All three subscales show high internal consistency with Cronbach's α coefficient values of 0.867, 0.819, and 0.903 and test-retest reliability was high (p < 0.001). Hence, the Sinhala version of the 16-item UWES-S is a valid and a reliable instrument to assess work engagement among collegiate cycle students in Sri Lanka.}, } @article {pmid29728123, year = {2018}, author = {Anastasiadis, C and Tsounis, A and Sarafis, P}, title = {The relationship between stress, social capital and quality of education among medical residents.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {274}, pmid = {29728123}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Education, Medical, Graduate/*standards ; Female ; Hospitals ; Humans ; Internship and Residency/*standards ; Male ; Occupational Stress/*psychology ; *Organizational Culture ; Physicians/*psychology ; *Social Capital ; *Social Support ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: The educational climate is a key factor in medical education. The study aims to examine the relationship between trainee doctors' perceptions of hospital educational environment, stress and social capital. A cross-sectional study among 104 trainee doctors working in a Greek public hospital was conducted. According to the main hypotheses, perceptions of clinical training are positively associated with social capital and negatively with stress.

RESULTS: Perceptions of autonomy dimension of training quality was positively related to community participation, tolerance of diversity and total social capital. Perceptions of teaching and social support dimensions of the quality of education were positively correlated with community participation. All training quality subscales were negatively correlated with almost all working stress subscales. Analysis revealed significantly higher scores in autonomy perceptions for those who evaluated their undergraduate studies positively. Females had a significantly lower score in perceptions of teaching and social support scales.}, } @article {pmid29728072, year = {2018}, author = {Gambetta, GA and Matthews, MA and Syvanen, M}, title = {The Xylella fastidosa RTX operons: evidence for the evolution of protein mosaics through novel genetic exchanges.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {329}, pmid = {29728072}, issn = {1471-2164}, support = {01-0712//California Department of Food and Agriculture (US)/ ; 2005-34442-15841//USDA/ ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/classification/genetics ; Base Sequence ; *Evolution, Molecular ; Gene Transfer, Horizontal ; *Genome, Bacterial ; Hemolysin Proteins/classification/*genetics ; Operon/*genetics ; Phylogeny ; Plant Diseases/microbiology ; Plant Leaves/genetics/metabolism/microbiology ; Sequence Alignment ; Vitis/genetics/metabolism/microbiology ; Xylella/*genetics ; }, abstract = {BACKGROUND: Xylella fastidiosa (Xf) is a gram negative bacterium inhabiting the plant vascular system. In most species this bacterium lives as a benign symbiote, but in several agriculturally important plants (e.g. coffee, citrus, grapevine) Xf is pathogenic. Xf has four loci encoding homologues to hemolysin RTX proteins, virulence factors involved in a wide range of plant pathogen interactions.

RESULTS: We show that all four genes are expressed during pathogenesis in grapevine. The sequences from these four genes have a complex repetitive structure. At the C-termini, sequence diversity between strains is what would be expected from orthologous genes. However, within strains there is no N-terminal homology, indicating these loci encode RTXs of different functions and/or specificities. More striking is that many of the orthologous loci between strains share this extreme variation at the N-termini. Thus these RTX orthologues are most easily visualized as fusions between the orthologous C-termini and different N-termini. Further, the four genes are found in operons having a peculiar structure with an extensively duplicated module encoding a small protein with homology to the N-terminal region of the full length RTX. Surprisingly, some of these small peptides are most similar not to their corresponding full length RTX, but to the N-termini of RTXs from other Xf strains, and even other remotely related species.

CONCLUSIONS: These results demonstrate that these genes are expressed in planta during pathogenesis. Their structure suggests extensive evolutionary restructuring through horizontal gene transfers and heterologous recombination mechanisms. The sum of the evidence suggests these repetitive modules are a novel kind of mobile genetic element.}, } @article {pmid29728068, year = {2018}, author = {Nomaguchi, T and Maeda, Y and Yoshino, T and Asahi, T and Tirichine, L and Bowler, C and Tanaka, T}, title = {Homoeolog expression bias in allopolyploid oleaginous marine diatom Fistulifera solaris.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {330}, pmid = {29728068}, issn = {1471-2164}, support = {09154495//Core Research for Evolutional Science and Technology/ ; ANR-12-BIME-0005//Agence Nationale de la Recherche/ ; ANR-10-LABX-54//Agence Nationale de la Recherche/ ; ANR-11-IDEX-0001-02//Agence Nationale de la Recherche/ ; Diatomite: 294823//European Research Council/International ; }, mesh = {Base Composition ; Biofuels ; Codon ; Diatoms/*genetics/metabolism ; *Gene Expression ; Genome ; Lipid Metabolism/genetics ; Metabolic Networks and Pathways/genetics ; Microalgae/genetics/metabolism ; Polyploidy ; Transcriptome ; }, abstract = {BACKGROUND: Allopolyploidy is a genomic structure wherein two or more sets of chromosomes derived from divergent parental species coexist within an organism. It is a prevalent genomic configuration in plants, as an important source of genetic variation, and also frequently confers environmental adaptability and increased crop productivity. We previously reported the oleaginous marine diatom Fistulifera solaris JPCC DA0580 to be a promising host for biofuel production and that its genome is allopolyploid, which had never previously been reported in eukaryotic microalgae. However, the study of allopolyploidy in F. solaris was hindered by the difficulty in classifying the homoeologous genes based on their progenitor origins, owing to the shortage of diatom genomic references.

RESULTS: In this study, the allopolyploid genome of F. solaris was tentatively classified into two pseudo-parental subgenomes using sequence analysis based on GC content and codon frequency in each homoeologous gene pair. This approach clearly separated the genome into two distinct fractions, subgenome Fso_h and Fso_l, which also showed the potency of codon usage analysis to differentiate the allopolyploid subgenome. Subsequent homoeolog expression bias analysis revealed that, although both subgenomes appear to contribute to global transcription, there were subgenomic preferences in approximately 61% of homoeologous gene pairs, and the majority of these genes showed continuous bias towards a specific subgenome during lipid accumulation. Additional promoter analysis indicated the possibility of promoter motifs involved in biased transcription of homoeologous genes. Among these subgenomic preferences, genes involved in lipid metabolic pathways showed interesting patterns in that biosynthetic and degradative pathways showed opposite subgenomic preferences, suggesting the possibility that the oleaginous characteristics of F. solaris derived from one of its progenitors.

CONCLUSIONS: We report the detailed genomic structure and expression patterns in the allopolyploid eukaryotic microalga F. solaris. The allele-specific patterns reported may contribute to the oleaginous characteristics of F. solaris and also suggest the robust oleaginous characteristics of one of its progenitors. Our data reveal novel aspects of allopolyploidy in a diatom that is not only important for evolutionary studies but may also be advantageous for biofuel production in microalgae.}, } @article {pmid29728067, year = {2018}, author = {Cemel, IA and Ha, N and Schermann, G and Yonekawa, S and Brunner, M}, title = {Correction to: The coding and noncoding transcriptome of Neurospora crassa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {325}, pmid = {29728067}, issn = {1471-2164}, abstract = {After publication of the original article [1], the authors noted that Additional files 6, 8 and 9 and their legends were incorrect.}, } @article {pmid29728066, year = {2018}, author = {Yeri, A and Courtright, A and Danielson, K and Hutchins, E and Alsop, E and Carlson, E and Hsieh, M and Ziegler, O and Das, A and Shah, RV and Rozowsky, J and Das, S and Van Keuren-Jensen, K}, title = {Evaluation of commercially available small RNASeq library preparation kits using low input RNA.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {331}, pmid = {29728066}, issn = {1471-2164}, support = {K23 HL127099/HL/NHLBI NIH HHS/United States ; UH3 TR000901//National Center for Advancing Translational Sciences/ ; UH3TR000891//National Center for Advancing Translational Sciences/ ; }, mesh = {Brain/metabolism ; Female ; *Gene Library ; High-Throughput Nucleotide Sequencing ; Humans ; Liver/metabolism ; MicroRNAs/analysis/chemistry ; Placenta/metabolism ; Pregnancy ; Principal Component Analysis ; RNA/chemistry/*metabolism ; Reagent Kits, Diagnostic ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Evolving interest in comprehensively profiling the full range of small RNAs present in small tissue biopsies and in circulating biofluids, and how the profile differs with disease, has launched small RNA sequencing (RNASeq) into more frequent use. However, known biases associated with small RNASeq, compounded by low RNA inputs, have been both a significant concern and a hurdle to widespread adoption. As RNASeq is becoming a viable choice for the discovery of small RNAs in low input samples and more labs are employing it, there should be benchmark datasets to test and evaluate the performance of new sequencing protocols and operators. In a recent publication from the National Institute of Standards and Technology, Pine et al., 2018, the investigators used a commercially available set of three tissues and tested performance across labs and platforms.

RESULTS: In this paper, we further tested the performance of low RNA input in three commonly used and commercially available RNASeq library preparation kits; NEB Next, NEXTFlex, and TruSeq small RNA library preparation. We evaluated the performance of the kits at two different sites, using three different tissues (brain, liver, and placenta) with high (1 μg) and low RNA (10 ng) input from tissue samples, or 5.0, 3.0, 2.0, 1.0, 0.5, and 0.2 ml starting volumes of plasma. As there has been a lack of robust validation platforms for differentially expressed miRNAs, we also compared low input RNASeq data with their expression profiles on three different platforms (Abcam Fireplex, HTG EdgeSeq, and Qiagen miRNome).

CONCLUSIONS: The concordance of RNASeq results on these three platforms was dependent on the RNA expression level; the higher the expression, the better the reproducibility. The results provide an extensive analysis of small RNASeq kit performance using low RNA input, and replication of these data on three downstream technologies.}, } @article {pmid29728062, year = {2018}, author = {Wu, WW and Phue, JN and Lee, CT and Lin, C and Xu, L and Wang, R and Zhang, Y and Shen, RF}, title = {Robust Sub-nanomolar Library Preparation for High Throughput Next Generation Sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {326}, pmid = {29728062}, issn = {1471-2164}, mesh = {Bordetella bronchiseptica/genetics ; DNA, Bacterial/chemistry/metabolism ; *Gene Library ; Genome, Bacterial ; *High-Throughput Nucleotide Sequencing ; RNA, Ribosomal, 16S/chemistry/genetics/metabolism ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Current library preparation protocols for Illumina HiSeq and MiSeq DNA sequencers require ≥2 nM initial library for subsequent loading of denatured cDNA onto flow cells. Such amounts are not always attainable from samples having a relatively low DNA or RNA input; or those for which a limited number of PCR amplification cycles is preferred (less PCR bias and/or more even coverage). A well-tested sub-nanomolar library preparation protocol for Illumina sequencers has however not been reported. The aim of this study is to provide a much needed working protocol for sub-nanomolar libraries to achieve outcomes as informative as those obtained with the higher library input (≥ 2 nM) recommended by Illumina's protocols.

RESULTS: Extensive studies were conducted to validate a robust sub-nanomolar (initial library of 100 pM) protocol using PhiX DNA (as a control), genomic DNA (Bordetella bronchiseptica and microbial mock community B for 16S rRNA gene sequencing), messenger RNA, microRNA, and other small noncoding RNA samples. The utility of our protocol was further explored for PhiX library concentrations as low as 25 pM, which generated only slightly fewer than 50% of the reads achieved under the standard Illumina protocol starting with > 2 nM.

CONCLUSIONS: A sub-nanomolar library preparation protocol (100 pM) could generate next generation sequencing (NGS) results as robust as the standard Illumina protocol. Following the sub-nanomolar protocol, libraries with initial concentrations as low as 25 pM could also be sequenced to yield satisfactory and reproducible sequencing results.}, } @article {pmid29728061, year = {2018}, author = {Tominaga, J and Nakahara, Y and Horikawa, D and Tanaka, A and Kondo, M and Kamei, Y and Takami, T and Sakamoto, W and Unno, K and Sakamoto, A and Shimada, H}, title = {Overexpression of the protein disulfide isomerase AtCYO1 in chloroplasts slows dark-induced senescence in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {80}, pmid = {29728061}, issn = {1471-2229}, mesh = {Aging/physiology ; Arabidopsis/enzymology/*physiology ; Arabidopsis Proteins/*metabolism/physiology ; Chlorophyll/metabolism ; Chloroplasts/enzymology/*physiology ; Darkness ; Gene Expression Regulation, Plant ; Photosystem II Protein Complex/metabolism ; Plant Leaves/enzymology/metabolism ; Protein Disulfide-Isomerases/*metabolism/physiology ; }, abstract = {BACKGROUND: Chlorophyll breakdown is the most obvious sign of leaf senescence. The chlorophyll catabolism pathway and the associated proteins/genes have been identified in considerable detail by genetic approaches combined with stay-green phenotyping. Arabidopsis CYO1 (AtCYO1), a protein disulfide reductase/isomerase localized in the thylakoid membrane, is hypothesized to assemble the photosystem by interacting with cysteine residues of the subunits.

RESULTS: In this study, we report that ectopic overexpression of AtCYO1 in leaves induces a stay-green phenotype during darkness, where oxidative conditions favor catabolism. In AtCYO1ox leaves, Fv/Fm and both chlorophyll a and chlorophyll b content remained high during dark-induced senescence. The thylakoid ultrastructure was preserved for a longer time in AtCYO1ox leaves than in wild type leaves. AtCYO1ox leaves maintained thylakoid chlorophyll-binding proteins associated with both PSII (D1, D2, CP43, CP47, LHCB2, and Cyt f) and PSI (PSA-A/B), as well as stromal proteins (Rubisco and ferredoxin-NADP+ reductase). AtCYO1ox did not affect senescence-inducible gene expression for chlorophyll catabolism or accumulation of chlorophyll catabolites.

CONCLUSIONS: Our results suggest that ectopic overexpression of AtCYO1 had a negative impact on the initiation of chlorophyll degradation and proteolysis within chloroplasts. Our findings cast new light on the redox regulation of protein disulfide bonds for the maintenance of functional chloroplasts.}, } @article {pmid29728060, year = {2018}, author = {Wang, M and Zhao, W and Gao, L and Zhao, L}, title = {Genome-wide profiling of long non-coding RNAs from tomato and a comparison with mRNAs associated with the regulation of fruit ripening.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {75}, pmid = {29728060}, issn = {1471-2229}, support = {31672158//National Natural Science Foundation of China/ ; }, mesh = {DNA Methylation ; Fruit/*genetics/growth & development ; Gene Expression Regulation, Developmental/genetics/physiology ; Gene Expression Regulation, Plant/genetics/physiology ; Genome, Plant/*genetics/physiology ; Lycopersicon esculentum/*genetics/growth & development ; RNA, Long Noncoding/*genetics/physiology ; RNA, Messenger/*genetics/physiology ; Transcriptome ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) are involved in multiple biological processes in both mammals and plants. There is growing evidence that they are associated with development; but their expression and regulation during fruit ripening in the model plant tomato (Solanum lycopersicum) has yet to be described.

RESULTS: Following integration of 134 RNA-seq data sets, we identified 79,322 putative lncRNAs, consisting of 70,635 lincRNAs, 8085 antisense non-coding RNAs (ancRNAs) and 602 sense lncRNAs (slncRNAs). lncRNAs had specific features that are distinct from mRNAs, including tissue-specificity, and shorter and fewer exons. Notably, more than 5000 of the novel lincRNAs were found to be expressed across the mature green (MG), breaker (BR) and breaker plus 7 days (BR + 7) developmental stages. The differently expressed lincRNAs had different DNA methylation profiles from the mRNAs.

CONCLUSIONS: Integrating transcriptome datasets and genome-wide screening enabled the identification of a comprehensive set of tomato lncRNAs. Here, we found that the lncRNAs DNA methylation profiles were different from those of mRNAs. This will help future investigation of lncRNA function, especially for the dissection of the molecular mechanisms involved in the regulation of fruit development.}, } @article {pmid29728059, year = {2018}, author = {Zhang, J and Wang, F and Liang, F and Zhang, Y and Ma, L and Wang, H and Liu, D}, title = {Functional analysis of a pathogenesis-related thaumatin-like protein gene TaLr35PR5 from wheat induced by leaf rust fungus.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {76}, pmid = {29728059}, issn = {1471-2229}, support = {31501623//National Natural Science Foundation of China/ ; }, mesh = {*Basidiomycota ; Disease Resistance/genetics ; Gene Silencing ; Genes, Plant/*genetics/physiology ; Plant Diseases/immunology/*microbiology ; Plant Immunity/*genetics ; Plant Proteins/*genetics/physiology ; Real-Time Polymerase Chain Reaction ; Triticum/*genetics/immunology/microbiology ; }, abstract = {BACKGROUND: Plants have evolved multifaceted defence mechanisms to resist pathogen infection. Production of the pathogenesis-related (PR) proteins in response to pathogen attack has been implicated in plant disease resistance specialized in systemic-acquired resistance (SAR). Our earlier studies have reported that a full length TaLr35PR5 gene, encoding a protein exhibiting amino acid and structural similarity to a sweet protein thaumatin, was isolated from wheat near-isogenic line TcLr35. The present study aims to understand the function of TaLr35PR5 gene in Lr35-mediated adult resistance to Puccinia triticina.

RESULTS: We determined that the TaLr35PR5 protein contained a functional secretion peptide by utilizing the yeast signal sequence trap system. Using a heterologous expression assay on onion epidermal cells we found that TaLr35PR5 protein was secreted into the apoplast of onion cell. Expression of TaLr35PR5 was significantly reduced in BSMV-induced gene silenced wheat plants, and pathology test on these silenced plants revealed that Lr35-mediated resistance phenotype was obviously altered, indicating that Lr35-mediated resistance was compromised.

CONCLUSIONS: All these findings strongly suggest that TaLr35PR5 is involved in Lr35-mediated adult wheat defense in response to leaf rust attack.}, } @article {pmid29728058, year = {2018}, author = {Li, J and He, YJ and Zhou, L and Liu, Y and Jiang, M and Ren, L and Chen, H}, title = {Correction to: Transcriptome profiling of genes related to light-induced anthocyanin biosynthesis in eggplant (Solanum melongena L.) before purple color becomes evident.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {324}, pmid = {29728058}, issn = {1471-2164}, abstract = {After publication of the original article [1] it was noted that in Additional file 1: Table S1, and Fig. 1, specific primer sequences were incorrect, and taken from Sme2.5_02154.1_g00001.1 rather than Sme2.5_13923.1_g00001.1.}, } @article {pmid29728057, year = {2018}, author = {Mondet, F and Rau, A and Klopp, C and Rohmer, M and Severac, D and Le Conte, Y and Alaux, C}, title = {Transcriptome profiling of the honeybee parasite Varroa destructor provides new biological insights into the mite adult life cycle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {328}, pmid = {29728057}, issn = {1471-2164}, support = {ANR-13-JS01-0001-01//ANR/ ; }, mesh = {Animals ; Arthropod Proteins/genetics ; Bees/*parasitology ; Female ; Gene Expression Profiling ; Host-Parasite Interactions/genetics ; Life Cycle Stages/genetics ; Male ; Reproduction/genetics ; *Transcriptome ; Varroidae/*genetics/physiology ; Vitellogenins/genetics ; }, abstract = {BACKGROUND: The parasite Varroa destructor represents a significant threat to honeybee colonies. Indeed, development of Varroa infestation within colonies, if left untreated, often leads to the death of the colony. Although its impact on bees has been extensively studied, less is known about its biology and the functional processes governing its adult life cycle and adaptation to its host. We therefore developed a full life cycle transcriptomic catalogue in adult Varroa females and included pairwise comparisons with males, artificially-reared and non-reproducing females (10 life cycle stages and conditions in total).

RESULTS: Extensive remodeling of the Varroa transcriptome was observed, with an upregulation of energetic and chitin metabolic processes during the initial and final phases of the life cycle (e.g. phoretic and post-oviposition stages), whereas during reproductive stages in brood cells genes showing functions related to transcriptional regulation were overexpressed. Several neurotransmitter and neuropeptide receptors involved in behavioural regulation, as well as active compounds of salivary glands, were also expressed at a higher level outside the reproductive stages. No difference was detected between artificially-reared phoretic females and their counterparts in colonies, or between females who failed to reproduce and females who successfully reproduced, indicating that phoretic individuals can be reared outside host colonies without impacting their physiology and that mechanisms underlying reproductive failure occur before oogenesis.

CONCLUSIONS: We discuss how these new findings reveal the remarkable adaptation of Varroa to its host biology and notably to the switch from living on adults to reproducing in sealed brood cells. By spanning the entire adult life cycle, our work captures the dynamic changes in the parasite gene expression and serves as a unique resource for deciphering Varroa biology and identifying new targets for mite control.}, } @article {pmid29728056, year = {2018}, author = {Fan, W and Ge, G and Liu, Y and Wang, W and Liu, L and Jia, Y}, title = {Proteomics integrated with metabolomics: analysis of the internal causes of nutrient changes in alfalfa at different growth stages.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {78}, pmid = {29728056}, issn = {1471-2229}, support = {31572461//National Natural Science Foundation of China/ ; CARS-35//Project of China Agriculture Research System/ ; }, mesh = {Carbohydrate Metabolism ; Gas Chromatography-Mass Spectrometry ; Mass Spectrometry ; Medicago sativa/growth & development/*metabolism ; Metabolomics ; Nutrients/*metabolism ; Nutritive Value ; Plant Leaves/growth & development/metabolism ; Plant Proteins/metabolism ; Polysaccharides/metabolism ; Proteomics ; }, abstract = {BACKGROUND: Alfalfa (Medicago sativa L.) is one of the most important forage resources in the world due to its high nutritive value. However, its nutritional quality decreases during the transition from budding to flowering. Previous research revealed a decreased crude protein content and increased fibre content in alfalfa forage harvested at later maturity stages, leading to a reduction in nutritional quality. However, the reasons for this phenomenon have not been explained at the molecular level.

RESULTS: In this study, leaves from the WL319HQ alfalfa cultivar were harvested at two developmental stages (budding and mid-flowering). The leaves were used to test the variable expression of proteins and metabolites during these stages. TMT-based quantitative proteomics and LC-MS/MS-based untargeted metabolomics methods were employed in this study. A total of 415 proteins and 49 metabolites showed at least a 1.2-fold difference in abundance during these stages. Most of the differentially expressed proteins and metabolites were involved in metabolic processes, including carbohydrate metabolism, starch and sucrose metabolism, phenylpropanoid biosynthesis, and biosynthesis of amino acids. Alfalfa leaves in mid-flowering contain less crude protein due to the decrease in L-glutamic acid content. Carbohydrate metabolism provides the raw material for the synthesis of hemicellulose, resulting in an increase in the hemicellulose content of the alfalfa leaves, leading to an increase in the NDF content. In addition, the increase in L-phenylalanine content could have provided the conditions necessary for lignin synthesis. These are the main factors leading to reductions in alfalfa relative feed value (RFV) and quality.

CONCLUSIONS: This study used joint proteomic and metabolomic analyses to elucidate the relationship between the reduction in the nutritional value of alfalfa and complex biological processes. This provides a theoretical basis for producing high-quality alfalfa hay and sets the stage for further research.}, } @article {pmid29728055, year = {2018}, author = {Zhang, C and Tang, G and Peng, X and Sun, F and Liu, S and Xi, Y}, title = {Long non-coding RNAs of switchgrass (Panicum virgatum L.) in multiple dehydration stresses.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {79}, pmid = {29728055}, issn = {1471-2229}, support = {31601370//National Natural Science Foundation of China/ ; 171305//China Postdoctoral Science Foundation/ ; Z109021616//PhD Start-up Foundation of Northwest A&F University/ ; Z109021705//Basic Scientific Research Foundation of Northwest A&F University/ ; }, mesh = {Abscisic Acid/metabolism ; Dehydration ; Ethylenes/metabolism ; Gene Expression Regulation, Plant ; Genes, Plant/genetics/physiology ; Panicum/genetics/*physiology ; Plant Growth Regulators/metabolism ; RNA, Long Noncoding/*genetics/physiology ; RNA, Messenger/genetics ; Real-Time Polymerase Chain Reaction ; Signal Transduction ; Starch/metabolism ; Sucrose/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) play important roles in plant growth and stress responses. Studies of lncRNAs in non-model plants are quite limited, especially those investigating multiple dehydration stresses. In this study, we identified novel lncRNAs and analyzed their functions in dehydration stress memory in switchgrass, an excellent biofuel feedstock and soil-conserving plant in the Gramineae family.

RESULTS: We analyzed genome-wide transcriptional profiles of leaves of 5-week-old switchgrass plantlets grown via tissue culture after primary and secondary dehydration stresses (D1 and D2) and identified 16,551 novel lncRNAs, including 4554 annotated lncRNAs (targeting 3574 genes), and 11,997 unknown lncRNAs. Gene ontology and pathway enrichment analysis of annotated genes showed that the differentially expressed lncRNAs were related to abscisic acid (ABA) and ethylene (ETH) biosynthesis and signal transduction, and to starch and sucrose metabolism. The upregulated lncRNAs and genes were related to ABA synthesis and its signal transduction, and to trehalose synthesis. Meanwhile, lncRNAs and genes related to ETH biosynthesis and signal transduction were suppressed. LncRNAs and genes involved in ABA metabolism were verified using quantitative real-time PCR, and the endogenous ABA content was determined via high performance liquid chromatography mass spectrometry (HPLC-MS). These results showed that ABA accumulated significantly during dehydration stress, especially in D2. Furthermore, we identified 307 dehydration stress memory lncRNAs, and the ratios of different memory types in switchgrass were similar to those in Arabidopsis and maize.

CONCLUSIONS: The molecular responses of switchgrass lncRNAs to multiple dehydration stresses were researched systematically, revealing novel information about their transcriptional regulatory behavior. This study provides new insights into the response mechanism to dehydration stress in plants. The lncRNAs and pathways identified in this study provide valuable information for genetic modification of switchgrass and other crops.}, } @article {pmid29728054, year = {2018}, author = {Nguyen, NH and Fitzgibbon, QP and Quinn, J and Smith, G and Battaglene, S and Knibb, W}, title = {Can metamorphosis survival during larval development in spiny lobster Sagmariasus verreauxi be improved through quantitative genetic inheritance?.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {27}, pmid = {29728054}, issn = {1471-2156}, support = {IH120100032//Australian Research Council/ ; }, abstract = {BACKGROUND: One of the major impediments to spiny lobster aquaculture is the high cost of hatchery production due to the long and complex larval cycle and poor survival during the many moult stages, especially at metamorphosis. We examined if the key trait of larval survival can be improved through selection by determining if genetic variance exists for this trait. Specifically, we report, for the first time, genetic parameters (heritability and correlations) for early survival rates recorded at five larval phases; early-phyllosoma stages (instars 1-6; S1), mid-phyllosoma stages (instars; 7-12; S2), late-phyllosoma stages (instars 13-17; S3), metamorphosis (S4) and puerulus stage (S5) in hatchery-reared spiny lobster Sagmariasus verreauxi.

RESULTS: The data were collected from a total of 235,060 larvae produced from 18 sires and 30 dams over nine years (2006 to 2014). Parentage of the offspring and full-sib families was verified using ten microsatellite markers. Analysis of variance components showed that the estimates of heritability for all the five phases of larval survival obtained from linear mixed model were generally similar to those obtained from threshold logistic generalised models (0.03-0.47 vs. 0.01-0.50). The heritability estimates for survival traits recorded in the early larval phases (S1 and S2) were higher than those estimated in later phases (S3, S4 and S5). The existence of the additive genetic component in larval survival traits indicate that they could be improved through selection. Both phenotypic and genetic correlations among the five survival measures studied were moderate to high and positive. The genetic associations between successive rearing periods were stronger than those that are further apart.

CONCLUSIONS: Our estimates of heritability and genetic correlations reported here in a spiny lobster species indicate that improvement in the early survival especially during metamorphosis can be achieved through genetic selection in this highly economic value species.}, } @article {pmid29728053, year = {2018}, author = {Fataftah, N and Mohr, C and Hajirezaei, MR and Wirén, NV and Humbeck, K}, title = {Changes in nitrogen availability lead to a reprogramming of pyruvate metabolism.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {77}, pmid = {29728053}, issn = {1471-2229}, mesh = {Amino Acids/metabolism ; Cellular Reprogramming ; Chlorophyll/metabolism ; Citric Acid Cycle ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Glycolysis ; Hordeum/metabolism ; Metabolic Networks and Pathways ; Nitrogen/*deficiency/metabolism ; Photosynthesis ; Polymerase Chain Reaction ; Pyruvic Acid/*metabolism ; RNA, Plant/metabolism ; }, abstract = {BACKGROUND: Low availability of nitrogen (N) severely affects plant growth at different levels, which can be reverted by the resupply of N. To unravel the critical steps in primary metabolism underlying the growth adjustment in response to changes in N availability, transcriptomic and comprehensive metabolite analyses were performed in barley using primary leaves at early and later stages of N deprivation, and after N resupply to N-deficient plants.

RESULT: N deficiency in leaves caused differential regulation of 1947 genes, mostly belonging to the functional classes photosynthesis, cell wall degradation, lipid degradation, amino acid degradation, transcription factors, phytohormone metabolism and receptor-like kinases. Interestingly, 62% of the genes responding to low N were regulated in the opposite direction after two days of N resupply. Reprogramming of gene transcription was linked to metabolic rearrangements and affected the metabolism of amino acids and sugars. The levels of major amino acids, including Glu, Asp, Ser, Gln, Gly, Thr, Ala, and Val, decreased during primary leaf age and, more pronounced, during low N-induced senescence, which was efficiently reverted after resupply of N. A significant decrease was observed for pyruvate and metabolites involved in the TCA cycle under low N, and this was reverted to initial levels after 5 days of N resupply. Correspondingly, transcript levels of genes coding for pyruvate kinase, pyruvate dehydrogenase, and pyruvate orthophosphate dikinase followed the same trend as related metabolites.

CONCLUSION: Our results show that upon N limitation a specific pathway for remobilization at the link between glycolysis and TCA cycle in barley is established that is at least partly regulated by a strict reprogramming of the gene coding for pyruvate orthophosphate dikinase. Further analysis of this pathway, its regulatory levels and biochemical changing of pyruvate metabolism enzymes in response to N availability is needed to determine the link between N status and primary metabolism.}, } @article {pmid29728051, year = {2018}, author = {Lopes, MB and Veríssimo, A and Carrasquinha, E and Casimiro, S and Beerenwinkel, N and Vinga, S}, title = {Ensemble outlier detection and gene selection in triple-negative breast cancer data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {168}, pmid = {29728051}, issn = {1471-2105}, abstract = {BACKGROUND: Learning accurate models from 'omics data is bringing many challenges due to their inherent high-dimensionality, e.g. the number of gene expression variables, and comparatively lower sample sizes, which leads to ill-posed inverse problems. Furthermore, the presence of outliers, either experimental errors or interesting abnormal clinical cases, may severely hamper a correct classification of patients and the identification of reliable biomarkers for a particular disease. We propose to address this problem through an ensemble classification setting based on distinct feature selection and modeling strategies, including logistic regression with elastic net regularization, Sparse Partial Least Squares - Discriminant Analysis (SPLS-DA) and Sparse Generalized PLS (SGPLS), coupled with an evaluation of the individuals' outlierness based on the Cook's distance. The consensus is achieved with the Rank Product statistics corrected for multiple testing, which gives a final list of sorted observations by their outlierness level.

RESULTS: We applied this strategy for the classification of Triple-Negative Breast Cancer (TNBC) RNA-Seq and clinical data from the Cancer Genome Atlas (TCGA). The detected 24 outliers were identified as putative mislabeled samples, corresponding to individuals with discrepant clinical labels for the HER2 receptor, but also individuals with abnormal expression values of ER, PR and HER2, contradictory with the corresponding clinical labels, which may invalidate the initial TNBC label. Moreover, the model consensus approach leads to the selection of a set of genes that may be linked to the disease. These results are robust to a resampling approach, either by selecting a subset of patients or a subset of genes, with a significant overlap of the outlier patients identified.

CONCLUSIONS: The proposed ensemble outlier detection approach constitutes a robust procedure to identify abnormal cases and consensus covariates, which may improve biomarker selection for precision medicine applications. The method can also be easily extended to other regression models and datasets.}, } @article {pmid29728050, year = {2018}, author = {Khan, T and Panday, SK and Ghosh, I}, title = {ProLego: tool for extracting and visualizing topological modules in protein structures.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {167}, pmid = {29728050}, issn = {1471-2105}, abstract = {BACKGROUND: In protein design, correct use of topology is among the initial and most critical feature. Meticulous selection of backbone topology aids in drastically reducing the structure search space. With ProLego, we present a server application to explore the component aspect of protein structures and provide an intuitive and efficient way to scan the protein topology space.

RESULT: We have implemented in-house developed "topological representation" in an automated-pipeline to extract protein topology from given protein structure. Using the topology string, ProLego, compares topology against a non-redundant extensive topology database (ProLegoDB) as well as extracts constituent topological modules. The platform offers interactive topology visualization graphs.

CONCLUSION: ProLego, provides an alternative but comprehensive way to scan and visualize protein topology along with an extensive database of protein topology. ProLego can be found at http://www.proteinlego.com.}, } @article {pmid29728049, year = {2018}, author = {Wu, J and Dai, W and Wu, L and Wang, J}, title = {Correction to: SALP, a new single-stranded DNA library preparation method especially useful for the high-throughput characterization of chromatin openness states.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {327}, pmid = {29728049}, issn = {1471-2164}, abstract = {After publication of the original article [1] the authors noted that the additional files had not been uploaded correctly.}, } @article {pmid29727635, year = {2018}, author = {Artap, S and Manderfield, LJ and Smith, CL and Poleshko, A and Aghajanian, H and See, K and Li, L and Jain, R and Epstein, JA}, title = {Endocardial Hippo signaling regulates myocardial growth and cardiogenesis.}, journal = {Developmental biology}, volume = {440}, number = {1}, pages = {22-30}, pmid = {29727635}, issn = {1095-564X}, support = {K08 HL119553/HL/NHLBI NIH HHS/United States ; R01 HL118768/HL/NHLBI NIH HHS/United States ; R35 HL140018/HL/NHLBI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/physiology ; Animals ; DNA-Binding Proteins/metabolism ; Endocardium/growth & development/metabolism/physiology ; Fibroblasts ; Heart/embryology/*growth & development ; Human Umbilical Vein Endothelial Cells ; Humans ; Mice ; Myocardium/*metabolism ; Neuregulin-1/metabolism ; Organogenesis ; Phosphoproteins/genetics/physiology ; Protein-Serine-Threonine Kinases/genetics/metabolism/*physiology ; Signal Transduction ; Transcription Factors/genetics/physiology ; }, abstract = {The Hippo signaling pathway has been implicated in control of cell and organ size, proliferation, and endothelial-mesenchymal transformation. This pathway impacts upon two partially redundant transcription cofactors, Yap and Taz, that interact with other factors, including members of the Tead family, to affect expression of downstream genes. Yap and Taz have been shown to regulate, in a cell-autonomous manner, myocardial proliferation, myocardial hypertrophy, regenerative potential, and overall size of the heart. Here, we show that Yap and Taz also play an instructive, non-cell-autonomous role in the endocardium of the developing heart to regulate myocardial growth through release of the paracrine factor, neuregulin. Without endocardial Yap and Taz, myocardial growth is impaired causing early post-natal lethality. Thus, the Hippo signaling pathway regulates cell size via both cell-autonomous and non-cell-autonomous mechanisms. Furthermore, these data suggest that Hippo may regulate organ size via a sensing and paracrine function in endothelial cells.}, } @article {pmid29727585, year = {2018}, author = {Schlebusch, CM and Jakobsson, M}, title = {Tales of Human Migration, Admixture, and Selection in Africa.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {405-428}, doi = {10.1146/annurev-genom-083117-021759}, pmid = {29727585}, issn = {1545-293X}, abstract = {In the last three decades, genetic studies have played an increasingly important role in exploring human history. They have helped to conclusively establish that anatomically modern humans first appeared in Africa roughly 250,000-350,000 years before present and subsequently migrated to other parts of the world. The history of humans in Africa is complex and includes demographic events that influenced patterns of genetic variation across the continent. Through genetic studies, it has become evident that deep African population history is captured by relationships among African hunter-gatherers, as the world's deepest population divergences occur among these groups, and that the deepest population divergence dates to 300,000 years before present. However, the spread of pastoralism and agriculture in the last few thousand years has shaped the geographic distribution of present-day Africans and their genetic diversity. With today's sequencing technologies, we can obtain full genome sequences from diverse sets of extant and prehistoric Africans. The coming years will contribute exciting new insights toward deciphering human evolutionary history in Africa.}, } @article {pmid29727584, year = {2018}, author = {Chappell, L and Russell, AJC and Voet, T}, title = {Single-Cell (Multi)omics Technologies.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {15-41}, doi = {10.1146/annurev-genom-091416-035324}, pmid = {29727584}, issn = {1545-293X}, abstract = {Single-cell multiomics technologies typically measure multiple types of molecule from the same individual cell, enabling more profound biological insight than can be inferred by analyzing each molecular layer from separate cells. These single-cell multiomics technologies can reveal cellular heterogeneity at multiple molecular layers within a population of cells and reveal how this variation is coupled or uncoupled between the captured omic layers. The data sets generated by these techniques have the potential to enable a deeper understanding of the key biological processes and mechanisms driving cellular heterogeneity and how they are linked with normal development and aging as well as disease etiology. This review details both established and novel single-cell mono- and multiomics technologies and considers their limitations, applications, and likely future developments.}, } @article {pmid29727582, year = {2018}, author = {Schneider-Poetsch, T and Yoshida, M}, title = {Along the Central Dogma-Controlling Gene Expression with Small Molecules.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {391-420}, doi = {10.1146/annurev-biochem-060614-033923}, pmid = {29727582}, issn = {1545-4509}, abstract = {The central dogma of molecular biology, that DNA is transcribed into RNA and RNA translated into protein, was coined in the early days of modern biology. Back in the 1950s and 1960s, bacterial genetics first opened the way toward understanding life as the genetically encoded interaction of macromolecules. As molecular biology progressed and our knowledge of gene control deepened, it became increasingly clear that expression relied on many more levels of regulation. In the process of dissecting mechanisms of gene expression, specific small-molecule inhibitors played an important role and became valuable tools of investigation. Small molecules offer significant advantages over genetic tools, as they allow inhibiting a process at any desired time point, whereas mutating or altering the gene of an important regulator would likely result in a dead organism. With the advent of modern sequencing technology, it has become possible to monitor global cellular effects of small-molecule treatment and thereby overcome the limitations of classical biochemistry, which usually looks at a biological system in isolation. This review focuses on several molecules, especially natural products, that have played an important role in dissecting gene expression and have opened up new fields of investigation as well as clinical venues for disease treatment.}, } @article {pmid29727060, year = {2018}, author = {Boscaro, V and Santoferrara, LF and Zhang, Q and Gentekaki, E and Syberg-Olsen, MJ and Del Campo, J and Keeling, PJ}, title = {EukRef-Ciliophora: a manually curated, phylogeny-based database of small subunit rRNA gene sequences of ciliates.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14264}, pmid = {29727060}, issn = {1462-2920}, abstract = {High-throughput sequencing (HTS) surveys, among the most common approaches currently used in environmental microbiology, require reliable reference databases to be correctly interpreted. The EukRef Initiative (eukref.org) is a community effort to manually screen available small subunit (SSU) rRNA gene sequences and produce a public, high-quality and informative framework of phylogeny-based taxonomic annotations. In the context of EukRef, we present a database for the monophyletic phylum Ciliophora, one of the most complex, diverse and ubiquitous protist groups. We retrieved more than 11 500 sequences of ciliates present in GenBank (28% from identified isolates and 72% from environmental surveys). Our approach included the inference of phylogenetic trees for every ciliate lineage and produced the largest SSU rRNA tree of the phylum Ciliophora to date. We flagged approximately 750 chimeric or low-quality sequences, improved the classification of 70% of GenBank entries and enriched environmental and literature metadata by 30%. The performance of EukRef-Ciliophora is superior to the current SILVA database in classifying HTS reads from a global marine survey. Comprehensive outputs are publicly available to make the new tool a useful guide for non-specialists and a quick reference for experts.}, } @article {pmid29727058, year = {2018}, author = {Wackett, LP and Robinson, SL}, title = {The future of environmental microbiology: a perspective.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14256}, pmid = {29727058}, issn = {1462-2920}, } @article {pmid29727057, year = {2018}, author = {Jing, X and Gou, H and Gong, Y and Su, X and Xu, and Ji, Y and Song, Y and Thompson, IP and Xu, J and Huang, WE}, title = {Raman-activated cell sorting and metagenomic sequencing revealing carbon-fixing bacteria in the ocean.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14268}, pmid = {29727057}, issn = {1462-2920}, abstract = {It is of great significance to understand CO2 fixation in the oceans. Using single cell Raman spectra (SCRS) as biochemical profiles, Raman activated cell ejection (RACE) was able to link phenotypes and genotypes of cells. Here, we show that mini-metagenomic sequences from RACE can be used as a reference to reconstruct nearly complete genomes of key functional bacteria by binning shotgun metagenomic sequencing data. By applying this approach to 13 C bicarbonate spiked seawater from euphotic zone of the Yellow Sea of China, the dominant bacteria Synechococcus spp. and Pelagibacter spp. were revealed and both of them contain carotenoid and were able to incorporate 13 C into the cells at the same time. Genetic analysis of the reconstructed genomes suggests that both Synechococcus spp. and Pelagibacter spp. contained all genes necessary for carotenoid synthesis, light energy harvesting and CO2 fixation. Interestingly, the reconstructed genome indicates that Pelagibacter spp. harbored intact sets of genes for β-carotene (precursor of retional), proteorhodopsin synthesis and anaplerotic CO2 fixation. This novel approach shines light on the role of marine 'microbial dark matter' in global carbon cycling, by linking yet-to-be-cultured Synechococcus spp. and Pelagibacter spp. to carbon fixation and flow activities in situ.}, } @article {pmid29727054, year = {2018}, author = {Kovalchuk, A and Mukrimin, M and Zeng, Z and Raffaello, T and Liu, M and Kasanen, R and Sun, H and Asiegbu, FO}, title = {Mycobiome analysis of asymptomatic and symptomatic Norway spruce trees naturally infected by the conifer pathogens Heterobasidion spp.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {532-541}, doi = {10.1111/1758-2229.12654}, pmid = {29727054}, issn = {1758-2229}, abstract = {Plant microbiome plays an important role in maintaining the host fitness. Despite a significant progress in our understanding of the plant microbiome achieved in the recent years, very little is known about the effect of plant pathogens on composition of microbial communities associated with trees. In this study, we analysed the mycobiome of different anatomic parts of asymptomatic and symptomatic Norway spruce trees naturally infected by Heterobasidion spp. We also investigated the primary impact of the disease on the fungal communities, which are associated with Norway spruce trees. Our results demonstrate that the structure of fungal communities residing in the wood differed significantly among symptomatic and asymptomatic Heterobasidion-infected trees. However, no significant differences were found in the other anatomic regions of the trees. The results also show that not only each of individual tree tissues (wood, bark, needles and roots) harbours a unique fungal community, but also that symptomatic trees were more susceptible to co-infection by other wood-degrading fungi compared to the asymptomatic ones.}, } @article {pmid29727053, year = {2018}, author = {Logares, R and Tesson, SVM and Canbäck, B and Pontarp, M and Hedlund, K and Rengefors, K}, title = {Contrasting prevalence of selection and drift in the community structuring of bacteria and microbial eukaryotes.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14265}, pmid = {29727053}, issn = {1462-2920}, abstract = {Whether or not communities of microbial eukaryotes are structured in the same way as bacteria is a general and poorly explored question in ecology. Here, we investigated this question in a set of planktonic lake microbiotas in Eastern Antarctica that represent a natural community ecology experiment. Most of the analysed lakes emerged from the sea during the last 6000 years, giving rise to waterbodies that originally contained marine microbiotas and that subsequently evolved into habitats ranging from freshwater to hypersaline. We show that habitat diversification has promoted selection driven by the salinity gradient in bacterial communities (explaining ∼ 72% of taxa turnover), while microeukaryotic counterparts were predominantly structured by ecological drift (∼72% of the turnover). Nevertheless, we also detected a number of microeukaryotes with specific responses to salinity, indicating that albeit minor, selection has had a role in the structuring of specific members of their communities. In sum, we conclude that microeukaryotes and bacteria inhabiting the same communities can be structured predominantly by different processes. This should be considered in future studies aiming to understand the mechanisms that shape microbial assemblages.}, } @article {pmid29727052, year = {2018}, author = {Danchin, A}, title = {Bacteria in the ageing gut: did the taming of fire promote a long human lifespan?.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14255}, pmid = {29727052}, issn = {1462-2920}, abstract = {Unique among animals as they evolved towards Homo sapiens, hominins progressively cooked their food on a routine basis. Cooked products are characterized by singular chemical compounds, derived from the pervasive Maillard reaction. This same reaction is omnipresent in normal metabolism involving carbonyls and amines, and its products accumulate with age. The gut microbiota acts as a first line of defence against the toxicity of cooked Maillard compounds, that also selectively shape the microbial flora, letting specific metabolites to reach the blood stream. Positive selection of metabolic functions allowed the body of hominins who tamed fire to use and dispose of these age-related compounds. I propose here that, as a hopeful accidental consequence, this resulted in extending human lifespan far beyond that of our great ape cousins. The limited data exploring the role of taming fire on the human genetic setup and on its microbiota is discussed in relation with ageing.}, } @article {pmid29727050, year = {2018}, author = {Yin, Z and Zhang, X and Wang, J and Yang, L and Feng, W and Chen, C and Gao, C and Zhang, H and Zheng, X and Wang, P and Zhang, Z}, title = {MoMip11, a MoRgs7-interacting protein, functions as a scaffolding protein to regulate cAMP signaling and pathogenicity in the rice blast fungus Magnaporthe oryzae.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3168-3185}, pmid = {29727050}, issn = {1462-2920}, support = {31530063//Natural Science Foundation of China/ ; R03 AI121460/AI/NIAID NIH HHS/United States ; R21 AI121451/AI/NIAID NIH HHS/United States ; 31325022//Natural Science Foundation of China/ ; BK20160074//Outstanding Youth Foundation of Jiangsu Province/ ; AI121460/GF/NIH HHS/United States ; AI121451/GF/NIH HHS/United States ; }, abstract = {The rice blast fungus Magnaporthe oryzae has eight regulators of G-protein signaling (RGS) and RGS-like proteins (MoRgs1 to MoRgs8) that exhibit both distinct and shared regulatory functions in the growth, differentiation and pathogenicity of the fungus. We found MoRgs7 with a unique RGS-seven transmembrane (7-TM) domain motif is localized to the highly dynamic tubule-vesicular compartments during early appressorium differentiation followed by gradually degradation. To explore whether this involves an active signal perception of MoRgs7, we identified a Gbeta-like/RACK1 protein homolog in M. oryzae MoMip11 that interacts with MoRgs7. Interestingly, MoMip11 selectively interacted with several components of the cAMP regulatory pathway, including Gα MoMagA and the high-affinity phosphodiesterase MoPdeH. We further showed that MoMip11 promotes MoMagA activation and suppresses MoPdeH activity thereby upregulating intracellular cAMP levels. Moreover, MoMip11 is required for the response to multiple stresses, a role also shared by Gbeta-like/RACK1 adaptor proteins. In summary, we revealed a unique mechanism by which MoMip11 links MoRgs7 and G-proteins to reugulate cAMP signaling, stress responses and pathogenicity of M. oryzae. Our studies revealed the multitude of regulatory networks that govern growth, development and pathogenicity in this important causal agent of rice blast.}, } @article {pmid29726925, year = {2018}, author = {Qi, W and Cascarano, MC and Schlapbach, R and Katharios, P and Vaughan, L and Seth-Smith, HMB}, title = {Ca. Endozoicomonas cretensis: A Novel Fish Pathogen Characterized by Genome Plasticity.}, journal = {Genome biology and evolution}, volume = {10}, number = {6}, pages = {1363-1374}, pmid = {29726925}, issn = {1759-6653}, mesh = {Animals ; Aquatic Organisms/microbiology ; Bacteria/*genetics ; Cell Plasticity/*genetics ; Coral Reefs ; DNA Transposable Elements/genetics ; Fishes/*microbiology ; Genome, Bacterial/*genetics ; Phylogeny ; Pseudogenes/genetics ; Sequence Analysis, DNA/methods ; Symbiosis/genetics ; Vertebrates/microbiology ; Virulence/genetics ; }, abstract = {Endozoicomonas bacteria are generally beneficial symbionts of diverse marine invertebrates including reef-building corals, sponges, sea squirts, sea slugs, molluscs, and Bryozoans. In contrast, the recently reported Ca. Endozoicomonas cretensis was identified as a vertebrate pathogen, causing epitheliocystis in fish larvae resulting in massive mortality. Here, we described the Ca. E. cretensis draft genome, currently undergoing genome decay as evidenced by massive insertion sequence (IS element) expansion and pseudogene formation. Many of the insertion sequences are also predicted to carry outward-directed promoters, implying that they may be able to modulate the expression of neighbouring coding sequences (CDSs). Comparative genomic analysis has revealed many Ca. E. cretensis-specific CDSs, phage integration and novel gene families. Potential virulence related CDSs and machineries were identified in the genome, including secretion systems and related effector proteins, and systems related to biofilm formation and directed cell movement. Mucin degradation would be of importance to a fish pathogen, and many candidate CDSs associated with this pathway have been identified. The genome may reflect a bacterium in the process of changing niche from symbiont to pathogen, through expansion of virulence genes and some loss of metabolic capacity.}, } @article {pmid29726609, year = {2018}, author = {Seyfullah, LJ and Beimforde, C and Dal Corso, J and Perrichot, V and Rikkinen, J and Schmidt, AR}, title = {Production and preservation of resins - past and present.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1684-1714}, doi = {10.1111/brv.12414}, pmid = {29726609}, issn = {1469-185X}, abstract = {Amber is fossilised plant resin. It can be used to provide insights into the terrestrial conditions at the time the original resin was exuded. Amber research thus can inform many aspects of palaeontology, from the recovery and description of enclosed fossil organisms (biological inclusions) to attempts at reconstruction of past climates and environments. Here we focus on the resin itself, the conditions under which it may have been exuded, and its potential path to fossilisation, rather than on enclosed fossils. It is noteworthy that not all plants produce resin, and that not all resins can (nor do) become amber. Given the recent upsurge in the number of amber deposits described, it is time to re-examine ambers from a botanical perspective. Here we summarise the state of knowledge about resin production in modern ecosystems, and review the biological and ecological aspects of resin production in plants. We also present new observations on conifer-derived resin exudation, with a particular focus on araucarian conifer trees. We suggest that besides disease, insect attacks and traumatic wounding from fires and storms, other factors such as tree architecture and local soil conditions are significant in creating and preserving resin outpourings. We also examine the transformation of resin into amber (maturation), focusing on geological aspects of amber deposit formation and preservation. We present new evidence that expands previous understanding of amber deposit formation. Specific geological conditions such as anoxic burial are essential in the creation of amber from resin deposits. We show that in the past, the production of large amounts of resin could have been linked to global climate changes and environmental disruption. We then highlight where the gaps in our knowledge still remain and potential future research directions.}, } @article {pmid29725767, year = {2018}, author = {Yu, XY and Zhai, JY and Wu, C and Zhang, CY and Shi, JY and Ding, LX and Wu, M}, title = {Pseudomonas pharmafabricae sp. nov., Isolated From Pharmaceutical Wastewater.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1119-1125}, pmid = {29725767}, issn = {1432-0991}, support = {2017C33030//Zhejiang Provincial Public Welfare Technology Applied Research Project/ ; 2017C33046//Zhejiang Provincial Public Welfare Technology Applied Research Project/ ; }, mesh = {Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/analysis ; Genes, Bacterial/genetics ; Genome, Bacterial/genetics ; Genotype ; *Pharmaceutical Preparations ; Phenotype ; Phospholipids/analysis ; *Phylogeny ; Pseudomonas/*classification/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Ubiquinone ; Waste Water/*microbiology ; }, abstract = {A Gram-stain-negative, aerobic, rod-shaped bacterial strain, designated ZYSR67-ZT, was isolated from a pharmaceutical wastewater sample collected from a chemical factory in Zhejiang, China. The strain was motile by a single polar flagellum and grew at 4-42 °C (optimum, 35 °C), pH 5.0-9.0 (optimum, 6.0) and 0-5.0% (w/v) NaCl (optimum, 2.0%). Based on multilocus sequence analysis using 16S rRNA, gyrB, rpoB and rpoD, the strain ZYSR67-ZT formed a distinct phylogenetic group in the genus Pseudomonas. The average nucleotide identity values between strain ZYSR67-ZT and the closely related 10 type strains of the Pseudomonas species were 75.8-78.6%. The in silico DNA-DNA hybridization values indicated that strain ZYSR67-ZT and the type strains of the Pseudomonas shared 21.4-23.1% DNA relatedness. The predominant isoprenoid quinone system was ubiquinone-9 while ubiquinone-8 was present in trace amounts. The major fatty acids (> 10%) identified were C12:0, C16:0, C18:1 ω7c and summed features 3 (C16:1 ω7c and/or iso-C15:0 2OH). The major polar lipids consisted of phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The genomic DNA G+C content was 62.6 mol%. On the basis of morphological, physiological and chemotaxonomic characteristics, together with the results of phylogenetic analysis, strain ZYSR67-ZT was proposed to represent a novel species of the genus Pseudomonas, named Pseudomonas pharmafabricae sp. nov.. The type strain is ZYSR67-ZT (= CGMCC 1.15498T = JCM 31306T).}, } @article {pmid29725703, year = {2018}, author = {Subramanian, H and Gatenby, RA}, title = {Chiral Monomers Ensure Orientational Specificity of Monomer Binding During Polymer Self-Replication.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {255-263}, pmid = {29725703}, issn = {1432-1432}, support = {U54CA193489//National Institutes of Health/ ; }, abstract = {Biomolecular homochirality is universally observed in living systems but the molecular and evolutionary dynamics that led to its emergence are unknown. In fact, there are significant disadvantages in using chiral monomers for polymerization, which include enantiomeric cross-inhibition in racemic medium and under-utilization of available resources for self-replication in the primordial environment. Nevertheless, most investigations of homochirality in living systems assume that the individual primordial monomers were chiral prior to the formation of self-replicating polymer and therefore focus on identifying a symmetry-breaking mechanism that might choose one enantiomer over the other in a racemic medium. Within the premise that the extant biomolecules are products of molecular evolution, we ask a related but distinct question: why is an achiral monomer molecule disfavored? Here we identify an evolutionary advantage for molecular evolution to choose chiral over achiral monomers to construct primordial self-replicating polymers. We argue that when polymerization is constrained to proceed in only one direction along the template, as in DNA, evolution favors chiral monomers and homochiral polymers. This evolutionary advantage stems from the ability of a chiral monomer to bond with the template in only one orientation relative to the template monomer, along the direction of polymerization. An achiral monomer, on the other hand, offers more than one possible orientation for bonding with the template monomer, due to the presence of symmetry elements in its structure, which would lead to inhibition of polymerization. We show that the requirement of orientational specificity leads to monomer chirality, by using a known relationship between rotational and reflection symmetry elements, within the constraint that the resultant polymers are helical.}, } @article {pmid29725499, year = {2018}, author = {Alvarez-Ponce, D and Weitzman, CL and Tillett, RL and Sandmeier, FC and Tracy, CR}, title = {High quality draft genome sequences of Mycoplasma agassizii strains PS6T and 723 isolated from Gopherus tortoises with upper respiratory tract disease.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {12}, pmid = {29725499}, issn = {1944-3277}, abstract = {Mycoplasma agassizii is one of the known causative agents of upper respiratory tract disease (URTD) in Mojave desert tortoises (Gopherus agassizii) and in gopher tortoises (Gopherus polyphemus). We sequenced the genomes of M. agassizii strains PS6T (ATCC 700616) and 723 (ATCC 700617) isolated from the upper respiratory tract of a Mojave desert tortoise and a gopher tortoise, respectively, both with signs of URTD. The PS6T genome assembly was organized in eight scaffolds, had a total length of 1,274,972 bp, a G + C content of 28.43%, and contained 979 protein-coding genes, 13 pseudogenes and 35 RNA genes. The 723 genome assembly was organized in 40 scaffolds, had a total length of 1,211,209 bp, a G + C content of 28.34%, and contained 955 protein-coding genes, seven pseudogenes, and 35 RNA genes. Both genomes exhibit a very similar organization and very similar numbers of genes in each functional category. Pairs of orthologous genes encode proteins that are 93.57% identical on average. Homology searches identified a putative cytadhesin. These genomes will enable studies that will help understand the molecular bases of pathogenicity of this and other Mycoplasma species.}, } @article {pmid29725113, year = {2018}, author = {Baggen, J and Thibaut, HJ and Strating, JRPM and van Kuppeveld, FJM}, title = {Publisher Correction: The life cycle of non-polio enteroviruses and how to target it.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {391}, doi = {10.1038/s41579-018-0022-3}, pmid = {29725113}, issn = {1740-1534}, abstract = {In the version of this Review originally published, co-author Hendrik Jan Thibaut's name was incorrectly indexed as "Jan Thibaut, H". It should have appeared as "Thibaut, HJ". This has now been corrected in all versions of the Review. The publisher apologizes to the authors and to readers for this error.}, } @article {pmid29725112, year = {2018}, author = {Wrighton, KH}, title = {Correction: Bridging the gap for lipopolysaccharides.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {391}, doi = {10.1038/s41579-018-0023-2}, pmid = {29725112}, issn = {1740-1534}, abstract = {The image that accompanies this article was wrongly credited to Macmillan Publishers Limited in the online version. The correct credit is iStockphoto. This has now been corrected online. We apologize to the readers for any confusion caused.}, } @article {pmid29725087, year = {2018}, author = {Genuth, NR and Barna, M}, title = {Heterogeneity and specialized functions of translation machinery: from genes to organisms.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {431-452}, doi = {10.1038/s41576-018-0008-z}, pmid = {29725087}, issn = {1471-0064}, support = {T32 GM007276/GM/NIGMS NIH HHS/United States ; }, abstract = {Regulation of mRNA translation offers the opportunity to diversify the expression and abundance of proteins made from individual gene products in cells, tissues and organisms. Emerging evidence has highlighted variation in the composition and activity of several large, highly conserved translation complexes as a means to differentially control gene expression. Heterogeneity and specialized functions of individual components of the ribosome and of the translation initiation factor complexes eIF3 and eIF4F, which are required for recruitment of the ribosome to the mRNA 5' untranslated region, have been identified. In this Review, we summarize the evidence for selective mRNA translation by components of these macromolecular complexes as a means to dynamically control the translation of the proteome in time and space. We further discuss the implications of this form of gene expression regulation for a growing number of human genetic disorders associated with mutations in the translation machinery.}, } @article {pmid29724958, year = {2018}, author = {Sanberg, PR}, title = {Finding reward in risk.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {570}, doi = {10.1126/science.360.6388.570}, pmid = {29724958}, issn = {1095-9203}, } @article {pmid29724957, year = {2018}, author = {Ling, GS and Crawford, G and Buang, N and Bartok, I and Tian, K and Thielens, NM and Bally, I and Harker, JA and Ashton-Rickardt, PG and Rutschmann, S and Strid, J and Botto, M}, title = {C1q restrains autoimmunity and viral infection by regulating CD8+ T cell metabolism.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {558-563}, doi = {10.1126/science.aao4555}, pmid = {29724957}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {Animals ; Autoantibodies/immunology ; Autoimmunity/genetics/*immunology ; CD8-Positive T-Lymphocytes/*metabolism ; Complement C1q/genetics/*physiology ; Complement C3/genetics/physiology ; Complement Pathway, Classical/genetics/immunology ; Disease Models, Animal ; Immunoglobulins/immunology ; Immunologic Memory/immunology ; Lupus Erythematosus, Systemic/genetics/*immunology ; Lymphocytic Choriomeningitis/genetics/*immunology ; Mice ; Mice, Mutant Strains ; }, abstract = {Deficiency of C1q, the initiator of the complement classical pathway, is associated with the development of systemic lupus erythematosus (SLE). Explaining this association in terms of abnormalities in the classical pathway alone remains problematic because C3 deficiency does not predispose to SLE. Here, using a mouse model of SLE, we demonstrate that C1q, but not C3, restrains the response to self-antigens by modulating the mitochondrial metabolism of CD8+ T cells, which can themselves propagate autoimmunity. C1q deficiency also triggers an exuberant effector CD8+ T cell response to chronic viral infection leading to lethal immunopathology. These data establish a link between C1q and CD8+ T cell metabolism and may explain how C1q protects against lupus, with implications for the role of viral infections in the perpetuation of autoimmunity.}, } @article {pmid29724956, year = {2018}, author = {Jenni, S and Harrison, SC}, title = {Structure of the DASH/Dam1 complex shows its role at the yeast kinetochore-microtubule interface.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {552-558}, doi = {10.1126/science.aar6436}, pmid = {29724956}, issn = {1095-9203}, support = {P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Cycle Proteins/*chemistry/ultrastructure ; Cryoelectron Microscopy ; Crystallography ; Kinetochores/chemistry/*metabolism/ultrastructure ; Microtubule-Associated Proteins/*chemistry/ultrastructure ; Microtubules/*metabolism ; Nuclear Proteins/chemistry/ultrastructure ; Protein Domains ; Protein Multimerization ; Protein Structure, Secondary ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/ultrastructure ; }, abstract = {Kinetochores connect mitotic-spindle microtubules with chromosomes, allowing microtubule depolymerization to pull chromosomes apart during anaphase while resisting detachment as the microtubule shortens. The heterodecameric DASH/Dam1 complex (DASH/Dam1c), an essential component of yeast kinetochores, assembles into a microtubule-encircling ring. The ring associates with rodlike Ndc80 complexes to organize the kinetochore-microtubule interface. We report the cryo-electron microscopy structure (at ~4.5-angstrom resolution) of a DASH/Dam1c ring and a molecular model of its ordered components, validated by evolutionary direct-coupling analysis. Integrating this structure with that of the Ndc80 complex and with published interaction data yields a molecular picture of kinetochore-microtubule attachment, including how flexible, C-terminal extensions of DASH/Dam1c subunits project and contact widely separated sites on the Ndc80 complex rod and how phosphorylation at previously identified sites might regulate kinetochore assembly.}, } @article {pmid29724955, year = {2018}, author = {Wudick, MM and Portes, MT and Michard, E and Rosas-Santiago, P and Lizzio, MA and Nunes, CO and Campos, C and Santa Cruz Damineli, D and Carvalho, JC and Lima, PT and Pantoja, O and Feijó, JA}, title = {CORNICHON sorting and regulation of GLR channels underlie pollen tube Ca2+ homeostasis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {533-536}, doi = {10.1126/science.aar6464}, pmid = {29724955}, issn = {1095-9203}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Calcium/*metabolism ; Calcium Channels/*metabolism ; Cell Membrane/metabolism ; Genetic Complementation Test ; Homeostasis ; Pollen Tube/genetics/*metabolism ; Protein Transport ; Receptors, Glutamate/genetics/*metabolism ; Saccharomyces cerevisiae/genetics ; }, abstract = {Compared to animals, evolution of plant calcium (Ca2+) physiology has led to a loss of proteins for influx and small ligand-operated control of cytosolic Ca2+, leaving many Ca2+ mechanisms unaccounted for. Here, we show a mechanism for sorting and activation of glutamate receptor-like channels (GLRs) by CORNICHON HOMOLOG (CNIH) proteins. Single mutants of pollen-expressed Arabidopsis thaliana GLRs (AtGLRs) showed growth and Ca2+ flux phenotypes expected for plasma membrane Ca2+ channels. However, higher-order mutants of AtGLR3.3 revealed phenotypes contradicting this assumption. These discrepancies could be explained by subcellular AtGLR localization, and we explored the implication of AtCNIHs in this sorting. We found that AtGLRs interact with AtCNIH pairs, yielding specific intracellular localizations. AtCNIHs further trigger AtGLR activity in mammalian cells without any ligand. These results reveal a regulatory mechanism underlying Ca2+ homeostasis by sorting and activation of AtGLRs by AtCNIHs.}, } @article {pmid29724954, year = {2018}, author = {Feng, J and Luo, J and Yang, P and Du, J and Kim, BS and Hu, H}, title = {Piezo2 channel-Merkel cell signaling modulates the conversion of touch to itch.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {530-533}, pmid = {29724954}, issn = {1095-9203}, support = {K08 AR065577/AR/NIAMS NIH HHS/United States ; R01 GM101218/GM/NIGMS NIH HHS/United States ; R01 AR070116/AR/NIAMS NIH HHS/United States ; R01 DK103901/DK/NIDDK NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Gene Deletion ; Ion Channels/genetics/*physiology ; Mechanotransduction, Cellular/genetics/*physiology ; Merkel Cells/drug effects/*physiology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Pruritus/genetics/*physiopathology ; Skin/*innervation ; *Touch ; }, abstract = {The somatosensory system relays many signals ranging from light touch to pain and itch. Touch is critical to spatial awareness and communication. However, in disease states, innocuous mechanical stimuli can provoke pathologic sensations such as mechanical itch (alloknesis). The molecular and cellular mechanisms that govern this conversion remain unknown. We found that in mice, alloknesis in aging and dry skin is associated with a loss of Merkel cells, the touch receptors in the skin. Targeted genetic deletion of Merkel cells and associated mechanosensitive Piezo2 channels in the skin was sufficient to produce alloknesis. Chemogenetic activation of Merkel cells protected against alloknesis in dry skin. This study reveals a previously unknown function of the cutaneous touch receptors and may provide insight into the development of alloknesis.}, } @article {pmid29724953, year = {2018}, author = {Zhou, X and Li, XY and Lu, K}, title = {Enhanced thermal stability of nanograined metals below a critical grain size.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {526-530}, doi = {10.1126/science.aar6941}, pmid = {29724953}, issn = {1095-9203}, abstract = {The limitation of nanograined materials is their strong tendency to coarsen at elevated temperatures. As grain size decreases into the nanoscale, grain coarsening occurs at much lower temperatures, as low as ambient temperatures for some metals. We discovered that nanometer-sized grains in pure copper and nickel produced from plastic deformation at low temperatures exhibit notable thermal stability below a critical grain size. The instability temperature rises substantially at smaller grain sizes, and the nanograins remain stable even above the recrystallization temperatures of coarse grains. The inherent thermal stability of nanograins originates from an autonomous grain boundary evolution to low-energy states due to activation of partial dislocations in plastic deformation.}, } @article {pmid29724952, year = {2018}, author = {Kazuma, E and Jung, J and Ueba, H and Trenary, M and Kim, Y}, title = {Real-space and real-time observation of a plasmon-induced chemical reaction of a single molecule.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {521-526}, doi = {10.1126/science.aao0872}, pmid = {29724952}, issn = {1095-9203}, abstract = {Plasmon-induced chemical reactions of molecules adsorbed on metal nanostructures are attracting increased attention for photocatalytic reactions. However, the mechanism remains controversial because of the difficulty of direct observation of the chemical reactions in the plasmonic field, which is strongly localized near the metal surface. We used a scanning tunneling microscope (STM) to achieve real-space and real-time observation of a plasmon-induced chemical reaction at the single-molecule level. A single dimethyl disulfide molecule on silver and copper surfaces was dissociated by the optically excited plasmon at the STM junction. The STM study combined with theoretical calculations shows that this plasmon-induced chemical reaction occurred by a direct intramolecular excitation mechanism.}, } @article {pmid29724951, year = {2018}, author = {Tan, Z and Chen, S and Peng, X and Zhang, L and Gao, C}, title = {Polyamide membranes with nanoscale Turing structures for water purification.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {518-521}, doi = {10.1126/science.aar6308}, pmid = {29724951}, issn = {1095-9203}, mesh = {*Membranes, Artificial ; *Nylons ; Permeability ; Polymerization ; Water Purification/*methods ; }, abstract = {The emergence of Turing structures is of fundamental importance, and designing these structures and developing their applications have practical effects in chemistry and biology. We use a facile route based on interfacial polymerization to generate Turing-type polyamide membranes for water purification. Manipulation of shapes by control of reaction conditions enabled the creation of membranes with bubble or tube structures. These membranes exhibit excellent water-salt separation performance that surpasses the upper-bound line of traditional desalination membranes. Furthermore, we show the existence of high water permeability sites in the Turing structures, where water transport through the membranes is enhanced.}, } @article {pmid29724950, year = {2018}, author = {Fenton, JL and Steimle, BC and Schaak, RE}, title = {Tunable intraparticle frameworks for creating complex heterostructured nanoparticle libraries.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {513-517}, doi = {10.1126/science.aar5597}, pmid = {29724950}, issn = {1095-9203}, abstract = {Complex heterostructured nanoparticles with precisely defined materials and interfaces are important for many applications. However, rationally incorporating such features into nanoparticles with rigorous morphology control remains a synthetic bottleneck. We define a modular divergent synthesis strategy that progressively transforms simple nanoparticle synthons into increasingly sophisticated products. We introduce a series of tunable interfaces into zero-, one-, and two-dimensional copper sulfide nanoparticles using cation exchange reactions. Subsequent manipulation of these intraparticle frameworks yielded a library of 47 distinct heterostructured metal sulfide derivatives, including particles that contain asymmetric, patchy, porous, and sculpted nanoarchitectures. This generalizable mix-and-match strategy provides predictable retrosynthetic pathways to complex nanoparticle features that are otherwise inaccessible.}, } @article {pmid29724949, year = {2018}, author = {Lee, CH and MacKinnon, R}, title = {Activation mechanism of a human SK-calmodulin channel complex elucidated by cryo-EM structures.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {508-513}, pmid = {29724949}, issn = {1095-9203}, support = {R01 GM043949/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Acetamides/chemistry ; Calmodulin/agonists/*chemistry/ultrastructure ; Cryoelectron Microscopy ; Humans ; Intermediate-Conductance Calcium-Activated Potassium Channels/agonists/*chemistry/ultrastructure ; Potassium Channel Blockers/chemistry ; Protein Domains ; Thiazines/chemistry ; Trityl Compounds/chemistry ; }, abstract = {Small-conductance Ca2+-activated K+ (SK) channels mediate neuron excitability and are associated with synaptic transmission and plasticity. They also regulate immune responses and the size of blood cells. Activation of SK channels requires calmodulin (CaM), but how CaM binds and opens SK channels has been unclear. Here we report cryo-electron microscopy (cryo-EM) structures of a human SK4-CaM channel complex in closed and activated states at 3.4- and 3.5-angstrom resolution, respectively. Four CaM molecules bind to one channel tetramer. Each lobe of CaM serves a distinct function: The C-lobe binds to the channel constitutively, whereas the N-lobe interacts with the S4-S5 linker in a Ca2+-dependent manner. The S4-S5 linker, which contains two distinct helices, undergoes conformational changes upon CaM binding to open the channel pore. These structures reveal the gating mechanism of SK channels and provide a basis for understanding SK channel pharmacology.}, } @article {pmid29724948, year = {2018}, author = {DeGraff, M}, title = {Linguistics' role in the right to education.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {502}, doi = {10.1126/science.aat5532}, pmid = {29724948}, issn = {1095-9203}, mesh = {Human Rights ; Humans ; *Linguistics ; *Teaching ; }, } @article {pmid29724947, year = {2018}, author = {Johns, DM and Oppenheimer, GM}, title = {Response-The sugar industry's influence on policy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {501-502}, doi = {10.1126/science.aat5208}, pmid = {29724947}, issn = {1095-9203}, mesh = {Humans ; *Industry ; Policy ; *Sugars ; }, } @article {pmid29724946, year = {2018}, author = {Kearns, C and Schmidt, L and Apollonio, D and Glantz, S}, title = {The sugar industry's influence on policy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {501}, doi = {10.1126/science.aat3763}, pmid = {29724946}, issn = {1095-9203}, mesh = {Humans ; *Industry ; Policy ; *Sugars ; }, } @article {pmid29724945, year = {2018}, author = {Marelli, L and Testa, G}, title = {Scrutinizing the EU General Data Protection Regulation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {496-498}, doi = {10.1126/science.aar5419}, pmid = {29724945}, issn = {1095-9203}, } @article {pmid29724944, year = {2018}, author = {Haseltine, F}, title = {Louise M. Slaughter (1929-2018).}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {495}, doi = {10.1126/science.aat8795}, pmid = {29724944}, issn = {1095-9203}, mesh = {Accidental Falls/*history/statistics & numerical data ; Federal Government/history ; History, 20th Century ; History, 21st Century ; Humans ; United States ; Women's Health Services/*history ; Women's Rights/*history ; }, } @article {pmid29724943, year = {2018}, author = {Mashour, GA}, title = {The controversial correlates of consciousness.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {493-494}, doi = {10.1126/science.aat5616}, pmid = {29724943}, issn = {1095-9203}, mesh = {*Brain ; *Consciousness ; Humans ; }, } @article {pmid29724942, year = {2018}, author = {Lewis, AH and Grandl, J}, title = {A cellular mechanism for age-induced itch.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {492-493}, doi = {10.1126/science.aat5617}, pmid = {29724942}, issn = {1095-9203}, support = {F32 NS094088/NS/NINDS NIH HHS/United States ; }, mesh = {*Aging ; Humans ; Merkel Cells/physiology ; *Pruritus ; }, } @article {pmid29724941, year = {2018}, author = {White, J and Rathod, PK}, title = {Indispensable malaria genes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {490-491}, doi = {10.1126/science.aat5092}, pmid = {29724941}, issn = {1095-9203}, support = {U19 AI089688/AI/NIAID NIH HHS/United States ; R01 AI093380/AI/NIAID NIH HHS/United States ; }, } @article {pmid29724940, year = {2018}, author = {Hidding, B}, title = {Sonochemistry of silicon hydrides.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {489-490}, doi = {10.1126/science.aap8005}, pmid = {29724940}, issn = {1095-9203}, } @article {pmid29724939, year = {2018}, author = {Barbier, EB and Burgess, JC and Dean, TJ}, title = {How to pay for saving biodiversity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {486-488}, doi = {10.1126/science.aar3454}, pmid = {29724939}, issn = {1095-9203}, mesh = {*Biodiversity ; Conservation of Natural Resources/*economics ; Private Sector/*economics ; }, } @article {pmid29724938, year = {2018}, author = {Wadman, M}, title = {A hidden history.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {480-485}, doi = {10.1126/science.360.6388.480}, pmid = {29724938}, issn = {1095-9203}, } @article {pmid29724937, year = {2018}, author = {Hutson, M}, title = {Has artificial intelligence become alchemy?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {478}, doi = {10.1126/science.360.6388.478}, pmid = {29724937}, issn = {1095-9203}, } @article {pmid29724936, year = {2018}, author = {Vogel, G}, title = {Fossils reveal how ancient birds got their beaks.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {477}, doi = {10.1126/science.360.6388.477}, pmid = {29724936}, issn = {1095-9203}, mesh = {Animals ; *Beak ; *Biological Evolution ; *Birds ; Fossils ; }, } @article {pmid29724935, year = {2018}, author = {Normile, D}, title = {Bucking global trends, Japan again embraces coal power.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {476-477}, doi = {10.1126/science.360.6388.476}, pmid = {29724935}, issn = {1095-9203}, } @article {pmid29724934, year = {2018}, author = {Normile, D}, title = {Korean thaw raises hopes for scientific cooperation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {475-476}, doi = {10.1126/science.360.6388.475}, pmid = {29724934}, issn = {1095-9203}, mesh = {Democratic People's Republic of Korea ; *Ecology ; *International Cooperation ; *Public Health ; Republic of Korea ; }, } @article {pmid29724933, year = {2018}, author = {Popkin, G}, title = {DOE unveils climate model in advance of global test.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {474-475}, doi = {10.1126/science.360.6388.474-b}, pmid = {29724933}, issn = {1095-9203}, } @article {pmid29724932, year = {2018}, author = {Rabesandratana, T}, title = {Europe moves to compete in global AI arms race.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {474}, doi = {10.1126/science.360.6388.474-a}, pmid = {29724932}, issn = {1095-9203}, } @article {pmid29724931, year = {2018}, author = {Cosier, S}, title = {Clever use of public data could sidestep new rule.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {473}, doi = {10.1126/science.360.6388.473}, pmid = {29724931}, issn = {1095-9203}, mesh = {*Access to Information ; Air Pollution/*legislation & jurisprudence ; Public Policy ; United States ; *United States Environmental Protection Agency ; }, } @article {pmid29724930, year = {2018}, author = {Cornwall, W}, title = {Critics see hidden goal in EPA data access rule.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {472-473}, doi = {10.1126/science.360.6388.472}, pmid = {29724930}, issn = {1095-9203}, mesh = {*Access to Information ; Air Pollution/*legislation & jurisprudence ; Goals ; *Information Dissemination ; Los Angeles ; *Particulate Matter ; Public Policy ; United States ; *United States Environmental Protection Agency ; }, } @article {pmid29724929, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {468-470}, doi = {10.1126/science.360.6388.468}, pmid = {29724929}, issn = {1095-9203}, } @article {pmid29724928, year = {2018}, author = {Glinos, K}, title = {Global data meet EU rules.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {467}, doi = {10.1126/science.aat9878}, pmid = {29724928}, issn = {1095-9203}, } @article {pmid29724927, year = {2018}, author = {}, title = {Erratum for the Report "Translocation of a gut pathobiont drives autoimmunity in mice and humans" by S. Manfredo Vieira, M. Hiltensperger, V. Kumar, D. Zegarra-Ruiz, C. Dehner, N. Khan, F. R. C. Costa, E. Tiniakou, T. Greiling, W. Ruff, A. Barbieri, C. Kriegel, S. S. Mehta, J. R. Knight, D. Jain, A. L. Goodman, M. A. Kriegel.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {}, doi = {10.1126/science.aat9922}, pmid = {29724927}, issn = {1095-9203}, } @article {pmid29724926, year = {2018}, author = {}, title = {Erratum for the Report "Seasonal and daily climate variation have opposite effects on species elevational range size" by W.-P. Chan, I-C. Chen, R. K. Colwell, W.-C. Liu, C. Huang, S.-F. Shen.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {}, doi = {10.1126/science.aat9919}, pmid = {29724926}, issn = {1095-9203}, } @article {pmid29724925, year = {2018}, author = {Zhang, M and Wang, C and Otto, TD and Oberstaller, J and Liao, X and Adapa, SR and Udenze, K and Bronner, IF and Casandra, D and Mayho, M and Brown, J and Li, S and Swanson, J and Rayner, JC and Jiang, RHY and Adams, JH}, title = {Uncovering the essential genes of the human malaria parasite Plasmodium falciparum by saturation mutagenesis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {}, doi = {10.1126/science.aap7847}, pmid = {29724925}, issn = {1095-9203}, support = {R01 AI094973/AI/NIAID NIH HHS/United States ; R01 AI117017/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antimalarials/pharmacology ; Artemisinins/pharmacology ; Conserved Sequence ; Drug Resistance/genetics ; Erythrocytes/parasitology ; Genes, Essential ; *Genes, Protozoan ; Genetic Fitness ; Humans ; Malaria Vaccines/genetics ; Malaria, Falciparum/*parasitology ; Mutagenesis ; Plasmodium falciparum/drug effects/*genetics/growth & development ; Reproduction, Asexual/*genetics ; }, abstract = {Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Despite decades of research, the distinct biology of these parasites has made it challenging to establish high-throughput genetic approaches to identify and prioritize therapeutic targets. Using transposon mutagenesis of P. falciparum in an approach that exploited its AT-rich genome, we generated more than 38,000 mutants, saturating the genome and defining mutability and fitness costs for over 87% of genes. Of 5399 genes, our study defined 2680 genes as essential for optimal growth of asexual blood stages in vitro. These essential genes are associated with drug resistance, represent leading vaccine candidates, and include approximately 1000 Plasmodium-conserved genes of unknown function. We validated this approach by testing proteasome pathways for individual mutants associated with artemisinin sensitivity.}, } @article {pmid29724924, year = {2018}, author = {Reznikov, N and Bilton, M and Lari, L and Stevens, MM and Kröger, R}, title = {Fractal-like hierarchical organization of bone begins at the nanoscale.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {}, pmid = {29724924}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Bone Density ; *Bone Substitutes ; Bone and Bones/*chemistry/*ultrastructure ; Calcification, Physiologic ; Electron Microscope Tomography ; Humans ; Microscopy, Electron, Transmission ; *Nanostructures ; }, abstract = {The components of bone assemble hierarchically to provide stiffness and toughness. However, the organization and relationship between bone's principal components-mineral and collagen-has not been clearly elucidated. Using three-dimensional electron tomography imaging and high-resolution two-dimensional electron microscopy, we demonstrate that bone mineral is hierarchically assembled beginning at the nanoscale: Needle-shaped mineral units merge laterally to form platelets, and these are further organized into stacks of roughly parallel platelets. These stacks coalesce into aggregates that exceed the lateral dimensions of the collagen fibrils and span adjacent fibrils as continuous, cross-fibrillar mineralization. On the basis of these observations, we present a structural model of hierarchy and continuity for the mineral phase, which contributes to the structural integrity of bone.}, } @article {pmid29724909, year = {2018}, author = {Caputi, L and Franke, J and Farrow, SC and Chung, K and Payne, RME and Nguyen, TD and Dang, TT and Soares Teto Carqueijeiro, I and Koudounas, K and Dugé de Bernonville, T and Ameyaw, B and Jones, DM and Vieira, IJC and Courdavault, V and O'Connor, SE}, title = {Missing enzymes in the biosynthesis of the anticancer drug vinblastine in Madagascar periwinkle.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1235-1239}, doi = {10.1126/science.aat4100}, pmid = {29724909}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Antineoplastic Agents, Phytogenic/*biosynthesis/chemistry ; Catharanthus/*enzymology/genetics ; *Genes, Plant ; Hydrolases/*genetics ; Indole Alkaloids/chemistry/metabolism ; Quinolines/chemistry/metabolism ; Vinblastine/*biosynthesis/chemistry ; Vinca Alkaloids/biosynthesis/chemistry ; }, abstract = {Vinblastine, a potent anticancer drug, is produced by Catharanthus roseus (Madagascar periwinkle) in small quantities, and heterologous reconstitution of vinblastine biosynthesis could provide an additional source of this drug. However, the chemistry underlying vinblastine synthesis makes identification of the biosynthetic genes challenging. Here we identify the two missing enzymes necessary for vinblastine biosynthesis in this plant: an oxidase and a reductase that isomerize stemmadenine acetate into dihydroprecondylocarpine acetate, which is then deacetoxylated and cyclized to either catharanthine or tabersonine via two hydrolases characterized herein. The pathways show how plants create chemical diversity and also enable development of heterologous platforms for generation of stemmadenine-derived bioactive compounds.}, } @article {pmid29724908, year = {2018}, author = {Song, T and Cai, X and Tu, MW and Zhang, X and Huang, B and Wilson, NP and Seyler, KL and Zhu, L and Taniguchi, T and Watanabe, K and McGuire, MA and Cobden, DH and Xiao, D and Yao, W and Xu, X}, title = {Giant tunneling magnetoresistance in spin-filter van der Waals heterostructures.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1214-1218}, doi = {10.1126/science.aar4851}, pmid = {29724908}, issn = {1095-9203}, abstract = {Magnetic multilayer devices that exploit magnetoresistance are the backbone of magnetic sensing and data storage technologies. Here, we report multiple-spin-filter magnetic tunnel junctions (sf-MTJs) based on van der Waals (vdW) heterostructures in which atomically thin chromium triiodide (CrI3) acts as a spin-filter tunnel barrier sandwiched between graphene contacts. We demonstrate tunneling magnetoresistance that is drastically enhanced with increasing CrI3 layer thickness, reaching a record 19,000% for magnetic multilayer structures using four-layer sf-MTJs at low temperatures. Using magnetic circular dichroism measurements, we attribute these effects to the intrinsic layer-by-layer antiferromagnetic ordering of the atomically thin CrI3 Our work reveals the possibility to push magnetic information storage to the atomically thin limit and highlights CrI3 as a superlative magnetic tunnel barrier for vdW heterostructure spintronic devices.}, } @article {pmid29724907, year = {2018}, author = {Tosches, MA and Yamawaki, TM and Naumann, RK and Jacobi, AA and Tushev, G and Laurent, G}, title = {Evolution of pallium, hippocampus, and cortical cell types revealed by single-cell transcriptomics in reptiles.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {881-888}, doi = {10.1126/science.aar4237}, pmid = {29724907}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; Cell Tracking/*methods ; GABAergic Neurons/classification/cytology ; Gene Expression Profiling/*methods ; Hippocampus/*cytology ; Neocortex/*cytology ; Neuroglia/classification/cytology ; Neurons/classification ; *Reptiles ; Single-Cell Analysis/*methods ; }, abstract = {Computations in the mammalian cortex are carried out by glutamatergic and γ-aminobutyric acid-releasing (GABAergic) neurons forming specialized circuits and areas. Here we asked how these neurons and areas evolved in amniotes. We built a gene expression atlas of the pallium of two reptilian species using large-scale single-cell messenger RNA sequencing. The transcriptomic signature of glutamatergic neurons in reptilian cortex suggests that mammalian neocortical layers are made of new cell types generated by diversification of ancestral gene-regulatory programs. By contrast, the diversity of reptilian cortical GABAergic neurons indicates that the interneuron classes known in mammals already existed in the common ancestor of all amniotes.}, } @article {pmid29724906, year = {2018}, author = {Iftikhar, Z and Anthore, A and Mitchell, AK and Parmentier, FD and Gennser, U and Ouerghi, A and Cavanna, A and Mora, C and Simon, P and Pierre, F}, title = {Tunable quantum criticality and super-ballistic transport in a "charge" Kondo circuit.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6395}, pages = {1315-1320}, doi = {10.1126/science.aan5592}, pmid = {29724906}, issn = {1095-9203}, abstract = {Quantum phase transitions (QPTs) are ubiquitous in strongly correlated materials. However, the microscopic complexity of these systems impedes the quantitative understanding of QPTs. We observed and thoroughly analyzed the rich strongly correlated physics in two profoundly dissimilar regimes of quantum criticality. With a circuit implementing a quantum simulator for the three-channel Kondo model, we reveal the universal scalings toward different low-temperature fixed points and along the multiple crossovers from quantum criticality. An unanticipated violation of the maximum conductance for ballistic free electrons is uncovered. The present charge pseudospin implementation of a Kondo impurity opens access to a broad variety of strongly correlated phenomena.}, } @article {pmid29724905, year = {2018}, author = {Donaldson, GP and Ladinsky, MS and Yu, KB and Sanders, JG and Yoo, BB and Chou, WC and Conner, ME and Earl, AM and Knight, R and Bjorkman, PJ and Mazmanian, SK}, title = {Gut microbiota utilize immunoglobulin A for mucosal colonization.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {795-800}, pmid = {29724905}, issn = {1095-9203}, support = {P50 GM082545/GM/NIGMS NIH HHS/United States ; T32 GM007616/GM/NIGMS NIH HHS/United States ; R01 AI041231/AI/NIAID NIH HHS/United States ; R01 GM099535/GM/NIGMS NIH HHS/United States ; R01 AI041239/AI/NIAID NIH HHS/United States ; P30 DK056338/DK/NIDDK NIH HHS/United States ; R21 DK083633/DK/NIDDK NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; R01 DK078938/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacterial Adhesion/immunology ; Bacterial Proteins/genetics/metabolism ; Bacteroides fragilis/genetics/*immunology/ultrastructure ; Cells, Cultured ; Gastrointestinal Microbiome/*immunology ; Humans ; Immunoglobulin A/*immunology ; Intestinal Mucosa/*immunology/*microbiology ; Mice ; Polysaccharides, Bacterial/immunology ; Symbiosis ; }, abstract = {The immune system responds vigorously to microbial infection while permitting lifelong colonization by the microbiome. Mechanisms that facilitate the establishment and stability of the gut microbiota remain poorly described. We found that a regulatory system in the prominent human commensal Bacteroides fragilis modulates its surface architecture to invite binding of immunoglobulin A (IgA) in mice. Specific immune recognition facilitated bacterial adherence to cultured intestinal epithelial cells and intimate association with the gut mucosal surface in vivo. The IgA response was required for B. fragilis (and other commensal species) to occupy a defined mucosal niche that mediates stable colonization of the gut through exclusion of exogenous competitors. Therefore, in addition to its role in pathogen clearance, we propose that IgA responses can be co-opted by the microbiome to engender robust host-microbial symbiosis.}, } @article {pmid29724904, year = {2018}, author = {Klein, DR and MacNeill, D and Lado, JL and Soriano, D and Navarro-Moratalla, E and Watanabe, K and Taniguchi, T and Manni, S and Canfield, P and Fernández-Rossier, J and Jarillo-Herrero, P}, title = {Probing magnetism in 2D van der Waals crystalline insulators via electron tunneling.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6394}, pages = {1218-1222}, doi = {10.1126/science.aar3617}, pmid = {29724904}, issn = {1095-9203}, abstract = {Magnetic insulators are a key resource for next-generation spintronic and topological devices. The family of layered metal halides promises varied magnetic states, including ultrathin insulating multiferroics, spin liquids, and ferromagnets, but device-oriented characterization methods are needed to unlock their potential. Here, we report tunneling through the layered magnetic insulator CrI3 as a function of temperature and applied magnetic field. We electrically detect the magnetic ground state and interlayer coupling and observe a field-induced metamagnetic transition. The metamagnetic transition results in magnetoresistances of 95, 300, and 550% for bilayer, trilayer, and tetralayer CrI3 barriers, respectively. We further measure inelastic tunneling spectra for our junctions, unveiling a rich spectrum consistent with collective magnetic excitations (magnons) in CrI3.}, } @article {pmid29724860, year = {2018}, author = {Garg, SG and Martin, WF}, title = {Asking endosymbionts to do an enzyme's job.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4543-E4544}, pmid = {29724860}, issn = {1091-6490}, mesh = {*Biological Evolution ; Enzymes/*metabolism ; Mitochondria ; *Symbiosis ; }, } @article {pmid29724859, year = {2018}, author = {Zachar, I and Szilágyi, A and Számadó, S and Szathmáry, E}, title = {Reply to Garg and Martin: The mechanism works.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4545-E4546}, pmid = {29724859}, issn = {1091-6490}, } @article {pmid29724858, year = {2018}, author = {Berg, J and Campbell, P and Kiermer, V and Raikhel, N and Sweet, D}, title = {Joint statement on EPA proposed rule and public availability of data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6098}, doi = {10.1073/pnas.1807459115}, pmid = {29724858}, issn = {1091-6490}, mesh = {Biomedical Research/*legislation & jurisprudence/*organization & administration ; Humans ; Information Dissemination/*legislation & jurisprudence ; United States ; United States Environmental Protection Agency/*legislation & jurisprudence ; }, } @article {pmid29724857, year = {2018}, author = {Osnas, JLD and Katabuchi, M and Kitajima, K and Wright, SJ and Reich, PB and Van Bael, SA and Kraft, NJB and Samaniego, MJ and Pacala, SW and Lichstein, JW}, title = {Divergent drivers of leaf trait variation within species, among species, and among functional groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5480-5485}, doi = {10.1073/pnas.1803989115}, pmid = {29724857}, issn = {1091-6490}, mesh = {Forests ; *Photosynthesis ; Plant Leaves/*chemistry/genetics/*metabolism ; Plants/*chemistry/classification/genetics/*metabolism ; *Quantitative Trait Loci ; Species Specificity ; }, abstract = {Understanding variation in leaf functional traits-including rates of photosynthesis and respiration and concentrations of nitrogen and phosphorus-is a fundamental challenge in plant ecophysiology. When expressed per unit leaf area, these traits typically increase with leaf mass per area (LMA) within species but are roughly independent of LMA across the global flora. LMA is determined by mass components with different biological functions, including photosynthetic mass that largely determines metabolic rates and contains most nitrogen and phosphorus, and structural mass that affects toughness and leaf lifespan (LL). A possible explanation for the contrasting trait relationships is that most LMA variation within species is associated with variation in photosynthetic mass, whereas most LMA variation across the global flora is associated with variation in structural mass. This hypothesis leads to the predictions that (i) gas exchange rates and nutrient concentrations per unit leaf area should increase strongly with LMA across species assemblages with low LL variance but should increase weakly with LMA across species assemblages with high LL variance and that (ii) controlling for LL variation should increase the strength of the above LMA relationships. We present analyses of intra- and interspecific trait variation from three tropical forest sites and interspecific analyses within functional groups in a global dataset that are consistent with the above predictions. Our analysis suggests that the qualitatively different trait relationships exhibited by different leaf assemblages can be understood by considering the degree to which photosynthetic and structural mass components contribute to LMA variation in a given assemblage.}, } @article {pmid29724856, year = {2018}, author = {Pucciariello, O and Legris, M and Costigliolo Rojas, C and Iglesias, MJ and Hernando, CE and Dezar, C and Vazquez, M and Yanovsky, MJ and Finlayson, SA and Prat, S and Casal, JJ}, title = {Rewiring of auxin signaling under persistent shade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {5612-5617}, pmid = {29724856}, issn = {1091-6490}, mesh = {Arabidopsis/drug effects/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Gene Expression Regulation, Plant/*drug effects ; Indoleacetic Acids/*pharmacology ; *Light ; Phytochrome/genetics/*metabolism ; Plant Growth Regulators/pharmacology ; *Plant Physiological Phenomena ; Signal Transduction ; }, abstract = {Light cues from neighboring vegetation rapidly initiate plant shade-avoidance responses. Despite our detailed knowledge of the early steps of this response, the molecular events under prolonged shade are largely unclear. Here we show that persistent neighbor cues reinforce growth responses in addition to promoting auxin-responsive gene expression in Arabidopsis and soybean. However, while the elevation of auxin levels is well established as an early event, in Arabidopsis, the response to prolonged shade occurs when auxin levels have declined to the prestimulation values. Remarkably, the sustained low activity of phytochrome B under prolonged shade led to (i) decreased levels of PHYTOCHROME INTERACTING FACTOR 4 (PIF4) in the cotyledons (the organs that supply auxin) along with increased levels in the vascular tissues of the stem, (ii) elevated expression of the PIF4 targets INDOLE-3-ACETIC ACID 19 (IAA19) and IAA29, which in turn reduced the expression of the growth-repressive IAA17 regulator, (iii) reduced abundance of AUXIN RESPONSE FACTOR 6, (iv) reduced expression of MIR393 and increased abundance of its targets, the auxin receptors, and (v) elevated auxin signaling as indicated by molecular markers. Mathematical and genetic analyses support the physiological role of this system-level rearrangement. We propose that prolonged shade rewires the connectivity between light and auxin signaling to sustain shade avoidance without enhanced auxin levels.}, } @article {pmid29724487, year = {2018}, author = {Rolshausen, G and Davies, TJ and Hendry, AP}, title = {Evolutionary Rates Standardized for Evolutionary Space: Perspectives on Trait Evolution.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {379-389}, doi = {10.1016/j.tree.2018.04.001}, pmid = {29724487}, issn = {1872-8383}, mesh = {*Biological Evolution ; Computer Simulation ; *Life History Traits ; Models, Biological ; *Phenotype ; *Phylogeny ; }, abstract = {Characterization of evolutionary radiations benefits from describing the temporal patterns of trait disparification. Comparative methods attempt this by evaluating the statistical fit of trait distributions to a phylogenetic hypothesis under assumed evolutionary models. However, it can be challenging to differentiate between models, with discriminatory power depending on the modes of evolution underlying trait distributions. We suggest rates of 'trait space saturation', standardized for limits to evolutionary change, as an additional tool to distinguish between modes of trait evolution. We evaluate this approach using simulations and show that trait space saturation can identify the true model of trait evolution in cases where traditional comparative methods can fail. We illustrate our approach using diverse empirical studies that represent contrasting scenarios of evolutionary radiation.}, } @article {pmid29724269, year = {2018}, author = {Parte, AC}, title = {LPSN - List of Prokaryotic names with Standing in Nomenclature (bacterio.net), 20 years on.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1825-1829}, doi = {10.1099/ijsem.0.002786}, pmid = {29724269}, issn = {1466-5034}, mesh = {Archaea/*classification ; Bacteria/*classification ; *Publications ; *Terminology as Topic ; }, abstract = {The List of Prokaryotic Names with Standing in Nomenclature (LPSN) was established in 1997 as the List of Bacterial Names with Standing in Nomenclature (LBSN); it quickly became a key online resource for anyone interested in bacterial and archaeal nomenclature and classification. This review looks at numbers of prokaryotic names published since the Approved Lists of Bacterial Names, current usage of LPSN and future developments.}, } @article {pmid29724186, year = {2018}, author = {Pratx, L and Rancurel, C and Da Rocha, M and Danchin, EGJ and Castagnone-Sereno, P and Abad, P and Perfus-Barbeoch, L}, title = {Genome-wide expert annotation of the epigenetic machinery of the plant-parasitic nematodes Meloidogyne spp., with a focus on the asexually reproducing species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {321}, pmid = {29724186}, issn = {1471-2164}, support = {ANR-11-LABX-0028-01//Agence Nationale de la Recherche/ ; ANR-13-JSV7-0006//Agence Nationale de la Recherche/ ; }, mesh = {Animals ; Argonaute Proteins/classification/genetics ; Caenorhabditis elegans/genetics ; DNA (Cytosine-5-)-Methyltransferases/classification/genetics ; DNA Methylation ; *Epigenesis, Genetic ; *Genome ; Histones/genetics/metabolism ; Phylogeny ; Plant Roots/parasitology ; Plants/*parasitology ; Protein Processing, Post-Translational/genetics ; Protozoan Proteins/classification/genetics ; RNA, Small Untranslated/genetics ; Reproduction, Asexual/*genetics ; Tylenchoidea/*genetics ; }, abstract = {BACKGROUND: The renewed interest in epigenetics has led to the understanding that both the environment and individual lifestyle can directly interact with the epigenome to influence its dynamics. Epigenetic phenomena are mediated by DNA methylation, stable chromatin modifications and non-coding RNA-associated gene silencing involving specific proteins called epigenetic factors. Multiple organisms, ranging from plants to yeast and mammals, have been used as model systems to study epigenetics. The interactions between parasites and their hosts are models of choice to study these mechanisms because the selective pressures are strong and the evolution is fast. The asexually reproducing root-knot nematodes (RKN) offer different advantages to study the processes and mechanisms involved in epigenetic regulation. RKN genomes sequencing and annotation have identified numerous genes, however, which of those are involved in the adaption to an environment and potentially relevant to the evolution of plant-parasitism is yet to be discovered.

RESULTS: Here, we used a functional comparative annotation strategy combining orthology data, mining of curated genomics as well as protein domain databases and phylogenetic reconstructions. Overall, we show that (i) neither RKN, nor the model nematode Caenorhabditis elegans possess any DNA methyltransferases (DNMT) (ii) RKN do not possess the complete machinery for DNA methylation on the 6th position of adenine (6mA) (iii) histone (de)acetylation and (de)methylation pathways are conserved between C. elegans and RKN, and the corresponding genes are amplified in asexually reproducing RKN (iv) some specific non-coding RNA families found in plant-parasitic nematodes are dissimilar from those in C. elegans. In the asexually reproducing RKN Meloidogyne incognita, expression data from various developmental stages supported the putative role of these proteins in epigenetic regulations.

CONCLUSIONS: Our results refine previous predictions on the epigenetic machinery of model species and constitute the most comprehensive description of epigenetic factors relevant to the plant-parasitic lifestyle and/or asexual mode of reproduction of RKN. Providing an atlas of epigenetic factors in RKN is an informative resource that will enable researchers to explore their potential role in adaptation of these parasites to their environment.}, } @article {pmid29724168, year = {2018}, author = {Ren, CG and Kong, CC and Xie, ZH}, title = {Role of abscisic acid in strigolactone-induced salt stress tolerance in arbuscular mycorrhizal Sesbania cannabina seedlings.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {74}, pmid = {29724168}, issn = {1471-2229}, support = {31601238//the National Natural Science Foundation of China/ ; 31370108//the National Natural Science Foundation of China/ ; 31570063//the National Natural Science Foundation of China/ ; 2017SYHZ0007//he High-tech Industrialization Cooperation Funds of Jilin province and the Chinese Academy of Science/ ; 2016ZH074//the Yantai Key Project of Research and Development Plan/ ; }, mesh = {Abscisic Acid/*physiology ; Hydrogen Peroxide/metabolism ; Lactones/*metabolism ; Mycorrhizae/*physiology ; Photosynthesis ; Plant Growth Regulators/*physiology ; Salt Stress ; Salt-Tolerant Plants/microbiology/*physiology ; Seedlings/*growth & development/microbiology/physiology ; Sesbania/microbiology/*physiology ; }, abstract = {BACKGROUND: Strigolactones (SLs) are considered to be a novel class of phytohormone involved in plant defense responses. Currently, their relationships with other plant hormones, such as abscisic acid (ABA), during responses to salinity stress are largely unknown.

RESULTS: In this study, the relationship between SL and ABA during the induction of H2O2 - mediated tolerance to salt stress were studied in arbuscular mycorrhizal (AM) Sesbania cannabina seedlings. The SL levels increased after ABA treatments and decreased when ABA biosynthesis was inhibited in AM plants. Additionally, the expression levels of SL-biosynthesis genes in AM plants increased following treatments with exogenous ABA and H2O2. Furthermore, ABA-induced SL production was blocked by a pre-treatment with dimethylthiourea, which scavenges H2O2. In contrast, ABA production was unaffected by dimethylthiourea. Abscisic acid induced only partial and transient increases in the salt tolerance of TIS108 (a SL synthesis inhibitor) treated AM plants, whereas SL induced considerable and prolonged increases in salt tolerance after a pre-treatment with tungstate.

CONCLUSIONS: These results strongly suggest that ABA is regulating the induction of salt tolerance by SL in AM S. cannabina seedlings.}, } @article {pmid29724166, year = {2018}, author = {Galpert, D and Fernández, A and Herrera, F and Antunes, A and Molina-Ruiz, R and Agüero-Chapin, G}, title = {Surveying alignment-free features for Ortholog detection in related yeast proteomes by using supervised big data classifiers.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {166}, pmid = {29724166}, issn = {1471-2105}, support = {SFRH/BPD/92978/2013//Fundação para a Ciência e a Tecnologia/International ; UID/Multi/04423/2013, PTDC/AAG-GLO/6887/2014//European Regional Development Fund (PT) and FCT funds/International ; }, mesh = {*Algorithms ; *Databases, Protein ; *Decision Trees ; *Proteome ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Sequence Analysis, Protein/*methods ; }, abstract = {BACKGROUND: The development of new ortholog detection algorithms and the improvement of existing ones are of major importance in functional genomics. We have previously introduced a successful supervised pairwise ortholog classification approach implemented in a big data platform that considered several pairwise protein features and the low ortholog pair ratios found between two annotated proteomes (Galpert, D et al., BioMed Research International, 2015). The supervised models were built and tested using a Saccharomycete yeast benchmark dataset proposed by Salichos and Rokas (2011). Despite several pairwise protein features being combined in a supervised big data approach; they all, to some extent were alignment-based features and the proposed algorithms were evaluated on a unique test set. Here, we aim to evaluate the impact of alignment-free features on the performance of supervised models implemented in the Spark big data platform for pairwise ortholog detection in several related yeast proteomes.

RESULTS: The Spark Random Forest and Decision Trees with oversampling and undersampling techniques, and built with only alignment-based similarity measures or combined with several alignment-free pairwise protein features showed the highest classification performance for ortholog detection in three yeast proteome pairs. Although such supervised approaches outperformed traditional methods, there were no significant differences between the exclusive use of alignment-based similarity measures and their combination with alignment-free features, even within the twilight zone of the studied proteomes. Just when alignment-based and alignment-free features were combined in Spark Decision Trees with imbalance management, a higher success rate (98.71%) within the twilight zone could be achieved for a yeast proteome pair that underwent a whole genome duplication. The feature selection study showed that alignment-based features were top-ranked for the best classifiers while the runners-up were alignment-free features related to amino acid composition.

CONCLUSIONS: The incorporation of alignment-free features in supervised big data models did not significantly improve ortholog detection in yeast proteomes regarding the classification qualities achieved with just alignment-based similarity measures. However, the similarity of their classification performance to that of traditional ortholog detection methods encourages the evaluation of other alignment-free protein pair descriptors in future research.}, } @article {pmid29724163, year = {2018}, author = {Clasen, FJ and Pierneef, RE and Slippers, B and Reva, O}, title = {EuGI: a novel resource for studying genomic islands to facilitate horizontal gene transfer detection in eukaryotes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {323}, pmid = {29724163}, issn = {1471-2164}, support = {93134//National Research Foundation (ZA)/ ; 93664//National Research Foundation (ZA)/ ; 102973//National Research Foundation (ZA)/ ; }, mesh = {Aspergillus fumigatus/genetics ; Comparative Genomic Hybridization ; Databases, Genetic ; Eukaryota/*genetics ; *Gene Transfer, Horizontal ; Genome, Fungal ; Genomic Islands ; Internet ; *User-Computer Interface ; }, abstract = {BACKGROUND: Genomic islands (GIs) are inserts of foreign DNA that have potentially arisen through horizontal gene transfer (HGT). There are evidences that GIs can contribute significantly to the evolution of prokaryotes. The acquisition of GIs through HGT in eukaryotes has, however, been largely unexplored. In this study, the previously developed GI prediction tool, SeqWord Gene Island Sniffer (SWGIS), is modified to predict GIs in eukaryotic chromosomes. Artificial simulations are used to estimate ratios of predicting false positive and false negative GIs by inserting GIs into different test chromosomes and performing the SWGIS v2.0 algorithm. Using SWGIS v2.0, GIs are then identified in 36 fungal, 22 protozoan and 8 invertebrate genomes.

RESULTS: SWGIS v2.0 predicts GIs in large eukaryotic chromosomes based on the atypical nucleotide composition of these regions. Averages for predicting false negative and false positive GIs were 20.1% and 11.01% respectively. A total of 10,550 GIs were identified in 66 eukaryotic species with 5299 of these GIs coding for at least one functional protein. The EuGI web-resource, freely accessible at http://eugi.bi.up.ac.za , was developed that allows browsing the database created from identified GIs and genes within GIs through an interactive and visual interface.

CONCLUSIONS: SWGIS v2.0 along with the EuGI database, which houses GIs identified in 66 different eukaryotic species, and the EuGI web-resource, provide the first comprehensive resource for studying HGT in eukaryotes.}, } @article {pmid29724161, year = {2018}, author = {Palombo, V and Loor, JJ and D'Andrea, M and Vailati-Riboni, M and Shahzad, K and Krogh, U and Theil, PK}, title = {Transcriptional profiling of swine mammary gland during the transition from colostrogenesis to lactogenesis using RNA sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {322}, pmid = {29724161}, issn = {1471-2164}, support = {3405-11-0342//Danish Ministry for Food, Agriculture and Fishery/ ; ILLU-538-914//National Institute of Food and Agriculture/ ; }, mesh = {Animals ; Carbohydrate Metabolism/genetics ; Colostrum/metabolism ; Female ; Gene Expression Profiling ; Gene Regulatory Networks/genetics ; Immune System/metabolism ; Lactation/metabolism ; Lipid Metabolism/genetics ; Mammary Glands, Animal/*metabolism ; Parturition ; RNA/chemistry/isolation & purification/metabolism ; Sequence Analysis, RNA ; Swine ; *Transcriptome ; Up-Regulation ; }, abstract = {BACKGROUND: Colostrum and milk are essential sources of antibodies and nutrients for the neonate, playing a key role in their survival and growth. Slight abnormalities in the timing of colostrogenesis/lactogenesis potentially threaten piglet survival. To further delineate the genes and transcription regulators implicated in the control of the transition from colostrogenesis to lactogenesis, we applied RNA-seq analysis of swine mammary gland tissue from late-gestation to farrowing. Three 2nd parity sows were used for mammary tissue biopsies on days 14, 10, 6 and 2 before (-) parturition and on day 1 after (+) parturition. A total of 15 mRNA libraries were sequenced on a HiSeq2500 (Illumina Inc.). The Dynamic Impact Approach and the Ingenuity Pathway Analysis were used for pathway analysis and gene network analysis, respectively.

RESULTS: A large number of differentially expressed genes were detected very close to parturition (-2d) and at farrowing (+ 1d). The results reflect the extraordinary metabolic changes in the swine mammary gland once it enters into the crucial phases of lactogenesis and underscore a strong transcriptional component in the control of colostrogenesis. There was marked upregulation of genes involved in synthesis of colostrum and main milk components (i.e. proteins, fat, lactose and antimicrobial factors) with a pivotal role of CSN1S2, LALBA, WAP, SAA2, and BTN1A1. The sustained activation of transcription regulators such as SREBP1 and XBP1 suggested they help coordinate these adaptations.

CONCLUSIONS: Overall, the precise timing for the transition from colostrogenesis to lactogenesis in swine mammary gland remains uncharacterized. However, our transcriptomic data support the hypothesis that the transition occurs before parturition. This is likely attributable to upregulation of a wide array of genes including those involved in 'Protein and Carbohydrate Metabolism', 'Immune System', 'Lipid Metabolism', 'PPAR signaling pathway' and 'Prolactin signaling pathway' along with the activation of transcription regulators controlling lipid synthesis and endoplasmic reticulum biogenesis and stress response.}, } @article {pmid29723841, year = {2018}, author = {Wyres, KL and Holt, KE}, title = {Klebsiella pneumoniae as a key trafficker of drug resistance genes from environmental to clinically important bacteria.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {131-139}, doi = {10.1016/j.mib.2018.04.004}, pmid = {29723841}, issn = {1879-0364}, abstract = {Klebsiella pneumoniae is an opportunistic bacterial pathogen known for its high frequency and diversity of antimicrobial resistance (AMR) genes. In addition to being a significant clinical problem in its own right, K. pneumoniae is the species within which several new AMR genes were first discovered before spreading to other pathogens (e.g. carbapenem-resistance genes KPC, OXA-48 and NDM-1). Whilst K. pneumoniae's contribution to the overall AMR crisis is impossible to quantify, current evidence suggests it has a wider ecological distribution, significantly more varied DNA composition, greater AMR gene diversity and a higher plasmid burden than other Gram negative opportunists. Hence we propose it plays a key role in disseminating AMR genes from environmental microbes to clinically important pathogens.}, } @article {pmid29723648, year = {2018}, author = {Carvalho, TP and Arce H, M and Reis, RE and Sabaj, MH}, title = {Molecular phylogeny of Banjo catfishes (Ostaryophisi: Siluriformes: Aspredinidae): A continental radiation in South American freshwaters.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {459-467}, doi = {10.1016/j.ympev.2018.04.039}, pmid = {29723648}, issn = {1095-9513}, abstract = {The family Aspredinidae is a moderately diverse and broadly distributed group of freshwater fishes endemic to South America. Commonly known as Banjo Catfishes, Aspredinidae currently includes 44 valid species divided among 13 genera. The first species-comprehensive hypothesis on phylogenetic relationships among aspredinids is presented. The phylogeny is based on DNA sequence data for five gene fragments (mitochondrial 16S and COI; nuclear RAG1, MYH6 and SH3PX3) from 114 individuals representing 31 species in 12 aspredinid genera. Analyses of molecular data support the monophyly of most genera (Bunocephalus excepted) and several higher-level relationships previously proposed by morphological studies. Based on the molecular phylogeny, a new suprageneric classification for Aspredinidae is proposed with the new monotypic subfamily Pseudobunocephalinae as the sister taxon to all other aspredinids.}, } @article {pmid29723647, year = {2018}, author = {Yoo, KO and Crowl, AA and Kim, KA and Cheon, KS and Cellinese, N}, title = {Origins of East Asian Campanuloideae (Campanulaceae) diversity.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {468-474}, doi = {10.1016/j.ympev.2018.04.040}, pmid = {29723647}, issn = {1095-9513}, abstract = {The Campanulaceae comprises approximately 2300 species that are distributed among five major lineages: Campanuloideae, Cyphioideae, Cyphocarpoideae, Lobelioideae, and Nemacladoideae. Of these, the Campanuloideae, a primarily Old World clade, has the largest diversity in East Asia. In this study, we reconstruct the phylogeny of East Asian Campanuloideae based on one nuclear gene (i.e., PPR70) and five plastid markers (i.e., atpB, matK, petD, rbcL, and trnL-trnF). We then use this phylogenetic framework to reconstruct the biogeographical history of the genus. Our molecular dataset includes 376 of the 1045 currently recognized species in the Campanuloideae. Of the 376 sampled species, 116 are from East Asia, representing ca. 60% of the East Asian Campanuloideae. Our PPR dataset included sequences for 156 accessions, representing 54 species, while our plastid dataset included sequences for 305 accessions, representing 354 species. Phylogenetic analyses recovered three large clades containing East Asian taxa: Campanulinae, Platycodinae, and Wahlenberginae. The historical assembly of Campanuloideae diversity in East Asia appears to have resulted from numerous, independent movements from Africa, Europe/W. Asia, and North America. Africa was inferred as the ancestral range for the Campanuloideae. Movement of the largest East Asian clade (Platycodinae) occurred at approximately 53.1 Ma (46.6-58.73 95% HPD) from Africa, with much of the current diversity found in East Asia having resulted from in situ diversification. Thirteen additional movements into East Asia, primarily from Europe/Western Asia, occurred subsequently. One dispersal event from western North America was also inferred. In contrast, only six movements out of East Asia were found. Our results suggest that East Asia has acted primarily as a sink for Campanuloideae diversity, with Europe, Western Asia, and Africa representing major source areas.}, } @article {pmid29723646, year = {2018}, author = {Shang, H and Sundue, M and Wei, R and Wei, XP and Luo, JJ and Liu, L and Schwartsburd, PB and Yan, YH and Zhang, XC}, title = {Hiya: A new genus segregated from Hypolepis in the fern family Dennstaedtiaceae, based on phylogenetic evidence and character evolution.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {449-458}, doi = {10.1016/j.ympev.2018.04.038}, pmid = {29723646}, issn = {1095-9513}, abstract = {The relationship of Hypolepis brooksiae, H. nigrescens, and H. scabristipes to the remainder of Hypolepis (Dennstaedtiaceae) has been questioned by previous authors based on their unique combination of morphological characters and different base chromosome number. Using four chloroplast genes including rbcL, atpA, rpL6, and rps4-trnS intergenic spacer (IGS) from 32 samples, representing 24 species of Dennstaedtiaceae, we recovered a clade comprising H. brooksiae and H. nigrescens, distinct from the remaining species of Hypolepis. This clade is resolved as sister to the clade comprising Blotiella, Paesia and Histiopteris. We reconstructed ancestral states of 16 morphological characters and found that this clade is distinguished by indeterminate, scandent leaves exhibiting rhythmic growth, provided with recurved black-tipped prickles, and stipule-like pinnules that protect the emerging crosier and pinnae departures, rachis-costa architecture where the adaxial sulcus is confluent with the next lower order, and a base chromosome number of x = 29. In light of this molecular and morphological evidence, we describe a new genus, Hiya, and provide nomenclatural combinations to accommodate the three known species segregated from Hypolepis: Hiya brooksiae, Hiya nigrescens, and Hiya scabristipes.}, } @article {pmid29722887, year = {2018}, author = {Kumar, S and Stecher, G and Li, M and Knyaz, C and Tamura, K}, title = {MEGA X: Molecular Evolutionary Genetics Analysis across Computing Platforms.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1547-1549}, pmid = {29722887}, issn = {1537-1719}, support = {R01 GM126567/GM/NIGMS NIH HHS/United States ; R01 LM012487/LM/NLM NIH HHS/United States ; }, abstract = {The Molecular Evolutionary Genetics Analysis (Mega) software implements many analytical methods and tools for phylogenomics and phylomedicine. Here, we report a transformation of Mega to enable cross-platform use on Microsoft Windows and Linux operating systems. Mega X does not require virtualization or emulation software and provides a uniform user experience across platforms. Mega X has additionally been upgraded to use multiple computing cores for many molecular evolutionary analyses. Mega X is available in two interfaces (graphical and command line) and can be downloaded from www.megasoftware.net free of charge.}, } @article {pmid29722884, year = {2018}, author = {Redmond, SN and MacInnis, BM and Bopp, S and Bei, AK and Ndiaye, D and Hartl, DL and Wirth, DF and Volkman, SK and Neafsey, DE}, title = {De Novo Mutations Resolve Disease Transmission Pathways in Clonal Malaria.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1678-1689}, pmid = {29722884}, issn = {1537-1719}, abstract = {Detecting de novo mutations in viral and bacterial pathogens enables researchers to reconstruct detailed networks of disease transmission and is a key technique in genomic epidemiology. However, these techniques have not yet been applied to the malaria parasite, Plasmodium falciparum, in which a larger genome, slower generation times, and a complex life cycle make them difficult to implement. Here, we demonstrate the viability of de novo mutation studies in P. falciparum for the first time. Using a combination of sequencing, library preparation, and genotyping methods that have been optimized for accuracy in low-complexity genomic regions, we have detected de novo mutations that distinguish nominally identical parasites from clonal lineages. Despite its slower evolutionary rate compared with bacterial or viral species, de novo mutation can be detected in P. falciparum across timescales of just 1-2 years and evolutionary rates in low-complexity regions of the genome can be up to twice that detected in the rest of the genome. The increased mutation rate allows the identification of separate clade expansions that cannot be found using previous genomic epidemiology approaches and could be a crucial tool for mapping residual transmission patterns in disease elimination campaigns and reintroduction scenarios.}, } @article {pmid29722880, year = {2018}, author = {Grantham, ME and Brisson, JA}, title = {Extensive Differential Splicing Underlies Phenotypically Plastic Aphid Morphs.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1934-1946}, pmid = {29722880}, issn = {1537-1719}, support = {R01 GM116867/GM/NIGMS NIH HHS/United States ; }, abstract = {Phenotypic plasticity results in a diversity of phenotypes from a single genotype in response to environmental cues. To understand the molecular basis of phenotypic plasticity, studies have focused on differential gene expression levels between environmentally determined phenotypes. The extent of alternative splicing differences among environmentally determined phenotypes has largely been understudied. Here, we study alternative splicing differences among plastically produced morphs of the pea aphid using RNA-sequence data. Pea aphids express two separate polyphenisms (plasticity with discrete phenotypes): a wing polyphenism consisting of winged and wingless females and a reproduction polyphenism consisting of asexual and sexual females. We find that pea aphids alternatively splice 34% of their genes, a high percentage for invertebrates. We also find that there is extensive use of differential spliced events between genetically identical, polyphenic females. These differentially spliced events are enriched for exon skipping and mutually exclusive exon events that maintain the open reading frame, suggesting that polyphenic morphs use alternative splicing to produce phenotype-biased proteins. Many genes that are differentially spliced between polyphenic morphs have putative functions associated with their respective phenotypes. We find that the majority of differentially spliced genes is not differentially expressed genes. Our results provide a rich candidate gene list for future functional studies that would not have been previously considered based solely on gene expression studies, such as ensconsin in the reproductive polyphenism, and CAKI in the wing polyphenism. Overall, this study suggests an important role for alternative splicing in the expression of environmentally determined phenotypes.}, } @article {pmid29722831, year = {2018}, author = {Kern, AD and Hahn, MW}, title = {The Neutral Theory in Light of Natural Selection.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1366-1371}, pmid = {29722831}, issn = {1537-1719}, support = {R01 GM117241/GM/NIGMS NIH HHS/United States ; }, abstract = {In this perspective, we evaluate the explanatory power of the neutral theory of molecular evolution, 50 years after its introduction by Kimura. We argue that the neutral theory was supported by unreliable theoretical and empirical evidence from the beginning, and that in light of modern, genome-scale data, we can firmly reject its universality. The ubiquity of adaptive variation both within and between species means that a more comprehensive theory of molecular evolution must be sought.}, } @article {pmid29722826, year = {2018}, author = {Hartmann, FE and Rodríguez de la Vega, RC and Brandenburg, JT and Carpentier, F and Giraud, T}, title = {Gene Presence-Absence Polymorphism in Castrating Anther-Smut Fungi: Recent Gene Gains and Phylogeographic Structure.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1298-1314}, pmid = {29722826}, issn = {1759-6653}, support = {309403//European Research Council/International ; }, mesh = {Adaptation, Biological/genetics ; Basidiomycota/classification/*genetics/isolation & purification ; *DNA Copy Number Variations ; Evolution, Molecular ; Genes, Fungal/*genetics ; Genome, Fungal ; Genomics ; Microsatellite Repeats ; Phylogeny ; Phylogeography ; Plant Diseases/*microbiology ; Polymorphism, Single Nucleotide/genetics ; Species Specificity ; }, abstract = {Gene presence-absence polymorphisms segregating within species are a significant source of genetic variation but have been little investigated to date in natural populations. In plant pathogens, the gain or loss of genes encoding proteins interacting directly with the host, such as secreted proteins, probably plays an important role in coevolution and local adaptation. We investigated gene presence-absence polymorphism in populations of two closely related species of castrating anther-smut fungi, Microbotryum lychnidis-dioicae (MvSl) and M. silenes-dioicae (MvSd), from across Europe, on the basis of Illumina genome sequencing data and high-quality genome references. We observed presence-absence polymorphism for 186 autosomal genes (2% of all genes) in MvSl, and only 51 autosomal genes in MvSd. Distinct genes displayed presence-absence polymorphism in the two species. Genes displaying presence-absence polymorphism were frequently located in subtelomeric and centromeric regions and close to repetitive elements, and comparison with outgroups indicated that most were present in a single species, being recently acquired through duplications in multiple-gene families. Gene presence-absence polymorphism in MvSl showed a phylogeographic structure corresponding to clusters detected based on SNPs. In addition, gene absence alleles were rare within species and skewed toward low-frequency variants. These findings are consistent with a deleterious or neutral effect for most gene presence-absence polymorphism. Some of the observed gene loss and gain events may however be adaptive, as suggested by the putative functions of the corresponding encoded proteins (e.g., secreted proteins) or their localization within previously identified selective sweeps. The adaptive roles in plant and anther-smut fungi interactions of candidate genes however need to be experimentally tested in future studies.}, } @article {pmid29722819, year = {2018}, author = {Satta, Y and Fujito, NT and Takahata, N}, title = {Nonequilibrium Neutral Theory for Hitchhikers.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1362-1365}, doi = {10.1093/molbev/msy093}, pmid = {29722819}, issn = {1537-1719}, abstract = {Selective sweep is a phenomenon of reduced variation at presumably neutrally evolving sites (hitchhikers) in the genome that is caused by the spread of a selected allele at a linked focal site, and is widely used to test for action of positive selection. Nonetheless, selective sweep may also provide an unprecedented opportunity for studying nonequilibrium properties of the neutral variation itself. We have demonstrated this possibility in relation to ancient selective sweep for modern human-specific changes and ongoing selective sweep for local population-specific changes.}, } @article {pmid29722813, year = {2018}, author = {Jobin, M and Schurz, H and Henn, BM}, title = {IMPUTOR: Phylogenetically Aware Software for Imputation of Errors in Next-Generation Sequencing.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1248-1254}, pmid = {29722813}, issn = {1759-6653}, mesh = {*Algorithms ; Chromosomes, Human, Y/classification/genetics ; Gene Frequency ; Genome-Wide Association Study ; Genomics/methods ; Haplotypes ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Male ; *Phylogeny ; Polymorphism, Single Nucleotide ; *Software ; }, abstract = {We introduce IMPUTOR, software for phylogenetically aware imputation of missing haploid nonrecombining genomic data. Targeted for next-generation sequencing data, IMPUTOR uses the principle of parsimony to impute data marked as missing due to low coverage. Along with efficiently imputing missing variant genotypes, IMPUTOR is capable of reliably and accurately correcting many nonmissing sites that represent spurious sequencing errors. Tests on simulated data show that IMPUTOR is capable of detecting many induced mutations without making erroneous imputations/corrections, with as many as 95% of missing sites imputed and 81% of errors corrected under optimal conditions. We tested IMPUTOR with human Y-chromosomes from pairs of close relatives and demonstrate IMPUTOR's efficacy in imputing missing and correcting erroneous calls.}, } @article {pmid29722810, year = {2018}, author = {Mohd-Assaad, N and McDonald, BA and Croll, D}, title = {Genome-Wide Detection of Genes Under Positive Selection in Worldwide Populations of the Barley Scald Pathogen.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1315-1332}, pmid = {29722810}, issn = {1759-6653}, mesh = {Adaptation, Physiological/genetics ; Agriculture ; Ascomycota/*genetics/isolation & purification ; Environment ; Genes, Fungal/*genetics/physiology ; Genome, Fungal ; Genotype ; Hordeum/*microbiology ; *Metagenomics ; Phylogeography ; Plant Diseases/microbiology ; Polymorphism, Single Nucleotide ; Selection, Genetic/*genetics ; }, abstract = {Coevolution between hosts and pathogens generates strong selection pressures to maintain resistance and infectivity, respectively. Genomes of plant pathogens often encode major effect loci for the ability to successfully infect specific host genotypes. Hence, spatial heterogeneity in host genotypes coupled with abiotic factors could lead to locally adapted pathogen populations. However, the genetic basis of local adaptation is poorly understood. Rhynchosporium commune, the pathogen causing barley scald disease, interacts at least partially in a gene-for-gene manner with its host. We analyzed global field populations of 125 R. commune isolates to identify candidate genes for local adaptation. Whole genome sequencing data showed that the pathogen is subdivided into three genetic clusters associated with distinct geographic and climatic regions. Using haplotype-based selection scans applied independently to each genetic cluster, we found strong evidence for selective sweeps throughout the genome. Comparisons of loci under selection among clusters revealed little overlap, suggesting that ecological differences associated with each cluster led to variable selection regimes. The strongest signals of selection were found predominantly in the two clusters composed of isolates from Central Europe and Ethiopia. The strongest selective sweep regions encoded protein functions related to biotic and abiotic stress responses. Selective sweep regions were enriched in genes encoding functions in cellular localization, protein transport activity, and DNA damage responses. In contrast to the prevailing view that a small number of gene-for-gene interactions govern plant pathogen evolution, our analyses suggest that the evolutionary trajectory is largely determined by spatially heterogeneous biotic and abiotic selection pressures.}, } @article {pmid29722806, year = {2018}, author = {Yates, MD and Barr Engel, S and Eddie, BJ and Lebedev, N and Malanoski, AP and Tender, LM}, title = {Redox-gradient driven electron transport in a mixed community anodic biofilm.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy081}, pmid = {29722806}, issn = {1574-6941}, abstract = {Here, we describe the long-distance (multi-cell-length) extracellular electron transport (LD-EET) that occurs in an anode-grown mixed community biofilm (MCB) enriched from river sediment that contains 3%-45% Geobacter spp. High signal-to-noise temperature-dependent electrochemical gating measurements (EGM) using interdigitated microelectrode arrays reveal a peak-shaped electrical conductivity vs. potential dependency, indicating MCB acts as a redox conductor, similar to pure culture anode-grown Geobacter sulfurreducens biofilms (GSB). EGM also reveal that the maximum sustained rate of LD-EET in MCB is comparable to GSB, and the same whether under acetate-oxidizing or acetate-free conditions. Voltammetry indicated that MCB possesses 3- to 5-fold less electrode-accessible redox cofactors than GSB, suggesting that MCB may be more efficiently organized than GSB for LD-EET or that a small portion of electrode accessible redox cofactors of GSB are involved in LD-EET. The activation energy for LD-EET (0.11 ± 0.01 eV) was comparable to GSB, consistent with the possible role of c-type cytochromes as LD-EET cofactors, detected in abundance by confocal resonance Raman microscopy. Taken together, the results demonstrate LD-EET for a mixed community anode-grown microbial biofilm that is remarkably similar to GSB even though it contains many different types of microorganisms and appears to utilize far fewer EET redox cofactors.}, } @article {pmid29722798, year = {2018}, author = {Li, H and Li, T and Qu, J}, title = {Stochastic processes govern bacterial communities from the blood of pikas and from their arthropod vectors.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy082}, pmid = {29722798}, issn = {1574-6941}, abstract = {Vector-borne microbes influence pathogen transmission and blood microbiomes, thereby affecting the emergence of infectious diseases. Thus, understanding the relationship between host and vector microbiomes is of importance. In this study, we investigated the bacterial community composition, diversity and assembly of the flea (Rhadinopsylla dahurica vicina), torsalo (Hypoderma curzonial), and the blood and gut of their shared pika host, Ochotona curzoniae. Bartonella, Sphingomonas and Bradyrhizobium were enriched in blood, while Wolbachia and Fusobacterium were more abundant in fleas and torsaloes. Most of potential pathogenic microbes (belonging to Fusobacterium, Rickettsia, Kingella, Porphyromonas, Bartonella and Mycoplasma) were present in the blood of pikas and their vectors. Blood communities were more similar to those from fleas than other sample types and were independent of host factors or geographical sites. Notably, blood microbes originate mainly from fleas rather than gut or torsaloes. Interestingly, the community assembly of blood, fleas or torsaloes was primarily governed by stochastic processes, while the gut microbiome was determined by deterministic processes. Ecological drift plays a dominant role in the assembly of blood and flea microbiomes. These results reflect the difficulty for predicting and regulating the microbial ecology of fleas for the prevention of potential microbiome-associated diseases.}, } @article {pmid29722645, year = {2018}, author = {Sheu, SY and Hsieh, TY and Young, CC and Chen, WM}, title = {Paracoccus fontiphilus sp. nov., isolated from a freshwater spring.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2054-2060}, doi = {10.1099/ijsem.0.002793}, pmid = {29722645}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/*microbiology ; Hydroxybutyrates ; Natural Springs/microbiology ; Nucleic Acid Hybridization ; Paracoccus/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Polyamines/chemistry ; Polyesters ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Taiwan ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {Strain MVW-1T, isolated from a freshwater spring in Taiwan, was characterized by using a polyphasic taxonomy approach. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain MVW-1T belongs to the genus Paracoccus and has the highest levels of sequence similarity to Paracoccus caeni MJ17T (97.6 %), Paracoccus sediminis CMB17T (97.4 %), Paracoccus angustae E6T (97.3 %) and Paracoccus acridae SCU-M53T (97.1 %). Cells were Gram-stain-negative, aerobic, poly-β-hydroxybutyrate-accumulating, non-motile, rod-shaped and formed light orange-coloured colonies. Optimal growth occurred at 20-25 °C, pH 6-7, and in the presence of 0-3 % NaCl. The major fatty acid of strain MVW-1T was C18 : 1ω7c. The polar lipid profile consisted of phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, diphosphatidylglycerol, an unidentified glycolipid, an unidentified aminolipid and three unidentified phospholipids. The predominant polyamines were spermidine, putrescine and cadaverine. The only isoprenoid quinone was Q-10. The genomic DNA G+C content of strain MVW-1T was 63.4 mol%. Strain MVW-1T exhibited less than 35 % DNA-DNA relatedness to P. caeni MJ17T, P. angustae E6T, P. sediminis CMB17T and P. acridae SCU-M53T. On the basis of phenotypic and genotypic properties and phylogenetic inference, strain MVW-1T should be classified in a novel species of the genus Paracoccus, for which the name Paracoccus fontiphilus sp. nov. is proposed. The type strain is MVW-1T (=BCRC 80974T=LMG 29554T=KCTC 52239T).}, } @article {pmid29722644, year = {2018}, author = {Sung, H and Kim, HS and Lee, JY and Kang, W and Kim, PS and Hyun, DW and Tak, EJ and Jung, MJ and Yun, JH and Kim, MS and Shin, NR and Whon, TW and Rho, JR and Park, SD and Shim, HE and Bae, JW}, title = {Oceanisphaera avium sp. nov., isolated from the gut of the cinereous vulture, Aegypius monachus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2068-2073}, doi = {10.1099/ijsem.0.002797}, pmid = {29722644}, issn = {1466-5034}, mesh = {Aeromonadaceae/*classification/genetics/isolation & purification ; Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Falconiformes/*microbiology ; Fatty Acids/chemistry ; Gastrointestinal Tract/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, catalase- and oxidase-positive, rod-shaped, flagellated bacterial strain, designated AMac2203T, was isolated from the gut of the cinereous vulture, Aegypiusmonachus, collected from the Seoul Grand Park Zoo, Republic of Korea. Strain AMac2203T grew optimally at 15-25 °C, pH 7-8 and in the presence of 3-5 % (w/v) NaCl. Phylogenetic analysis revealed 97.4-97.9 % and 96.9-97.3 % sequence similarities of the 16S rRNA genes to its counterparts in Oceanisphaera profunda SM1222T and Oceanisphaera ostreae T-w6T, respectively. The predominant fatty acids (>10 %) of strain AMac2203T were summed feature 3 (C16 : 0ω7c and/or C16 : 1ω6c, 33.6 %), summed feature 8 (C18 : 1ω7c, 24.5 %) and C16 : 0 (19.9 %). The primary isoprenoid quinone was ubiquinone-8. Polar lipids included phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified amino lipid and an unidentified lipid. Based on complete genome sequencing of strain AMac2203T and the closest related type strain, O. profunda, the OrthoANI value is 77.5 %, which is below the 95 % cut-off for species demarcation. The genomic DNA G+C content of strain AMac2203T is 47.1 mol%. Thus, strain AMac2203T represents a novel species candidate of the genus Oceanisphaera. We propose the name Oceanisphaeraavium sp. nov., with strain AMac2203T (=KCTC 62118T=JCM 32207T) as the type strain.}, } @article {pmid29721580, year = {2018}, author = {Kleinnijenhuis, AJ and van Holthoon, FL}, title = {Domain-Specific Proteogenomic Analysis of Collagens to Evaluate De Novo Sequencing Results and Database Information.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {293-302}, pmid = {29721580}, issn = {1432-1432}, abstract = {Collagen is an important structural protein and the most abundant protein in mammals. In several research fields, structural analysis of collagens is performed. Fibrillar collagens almost entirely consist of continuous repeats of GXY, where G is glycine, X is often proline or alanine and Y is often hydroxyproline or alanine. In the present study, the collagen structure was investigated in detail at the nucleotide, codon group, amino acid and target peptide level using sequence analyses. One of the most important findings was that a selection of codon groups is predominantly involved in amino acid changes between closely related collagens and that other change routes come up when collagens are less related. The findings of the sequence analyses were used to evaluate reported sequences of non-avian dinosaur species and database entries of duck and chicken collagen. The duck assessment was supported by an experimental data set, obtained by collagen extraction from duck skin and subsequent digestion and LC-MS analysis. It was found that database entries of chicken and duck collagen 3α1 contained unreliable features, such as missing parts, no continuous GXY pattern and too many interspecies differences. As an example, the erroneous nature of one of these unreliable features was confirmed experimentally using LC-MS. Finally, dino and bird collagen 1α1 were compared. The presented results will show that performing a domain-specific proteogenomic analysis provides very useful information to assess de novo sequencing results and database information of collagens. Furthermore, it offers deeper insight in the functional restrictions and routes of evolutionary divergence.}, } @article {pmid29721304, year = {2018}, author = {Moner, AM and Furtado, A and Chivers, I and Fox, G and Crayn, D and Henry, RJ}, title = {Diversity and evolution of rice progenitors in Australia.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4360-4366}, pmid = {29721304}, issn = {2045-7758}, abstract = {In the thousands of years of rice domestication in Asia, many useful genes have been lost from the gene pool. Wild rice is a key source of diversity for domesticated rice. Genome sequencing has suggested that the wild rice populations in northern Australia may include novel taxa, within the AA genome group of close (interfertile) wild relatives of domesticated rice that have evolved independently due to geographic separation and been isolated from the loss of diversity associated with gene flow from the large populations of domesticated rice in Asia. Australian wild rice was collected from 27 sites from Townsville to the northern tip of Cape York. Whole chloroplast genome sequences and 4,555 nuclear gene sequences (more than 8 Mbp) were used to explore genetic relationships between these populations and other wild and domesticated rices. Analysis of the chloroplast and nuclear data showed very clear evidence of distinctness from other AA genome Oryza species with significant divergence between Australian populations. Phylogenetic analysis suggested the Australian populations represent the earliest-branching AA genome lineages and may be critical resources for global rice food security. Nuclear genome analysis demonstrated that the diverse O. meridionalis populations were sister to all other AA genome taxa while the Australian O. rufipogon-like populations were associated with the clade that included domesticated rice. Populations of apparent hybrids between the taxa were also identified suggesting ongoing dynamic evolution of wild rice in Australia. These introgressions model events similar to those likely to have been involved in the domestication of rice.}, } @article {pmid29721303, year = {2018}, author = {Yang, J and Wu, Q and Xiao, R and Zhao, J and Chen, J and Jiao, X}, title = {Seasonal variations in body melanism and size of the wolf spider Pardosa astrigera (Araneae: Lycosidae).}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4352-4359}, pmid = {29721303}, issn = {2045-7758}, abstract = {Variations in species morphology and life-history traits strongly correlate with geographic and climatic characteristics. Most studies on morphological variations in animals focus on ectotherms distributed on a large geographic scale across latitudinal and/or altitudinal gradient. However, the morphological variations of spiders living in the same habitats across different seasons have not been reported. In this study, we used the wolf spider, Pardosa astrigera, as a model to determine seasonal differences in adult body size, melanism, fecundity, and egg diameter both in the overwintering and the first generation for 2010 and 2016. The results showed that in 2010, both females and males of the overwintering generation were significantly darker than the first generation. Moreover, the overwintering females were markedly larger and produced more and bigger eggs than the first generation in both 2010 and 2016. Considering the overwintering P. astrigera experiencing low temperature and/or desiccation stress, these results suggest that substantially darker and larger body of the overwintering generation is adaptive to adverse conditions.}, } @article {pmid29721302, year = {2018}, author = {McHuron, EA and Peterson, SH and Hückstädt, LA and Melin, SR and Harris, JD and Costa, DP}, title = {The energetic consequences of behavioral variation in a marine carnivore.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4340-4351}, pmid = {29721302}, issn = {2045-7758}, abstract = {Intraspecific variability in foraging behavior has been documented across a range of taxonomic groups, yet the energetic consequences of this variation are not well understood for many species. Understanding the effect of behavioral variation on energy expenditure and acquisition is particularly crucial for mammalian carnivores because they have high energy requirements that place considerable pressure on prey populations. To determine the influence of behavior on energy expenditure and balance, we combined simultaneous measurements of at-sea field metabolic rate (FMR) and foraging behavior in a marine carnivore that exhibits intraspecific behavioral variation, the California sea lion (Zalophus californianus). Sea lions exhibited variability in at-sea FMR, with some individuals expending energy at a maximum of twice the rate of others. This variation was in part attributable to differences in diving behavior that may have been reflective of diet; however, this was only true for sea lions using a foraging strategy consisting of epipelagic (<200 m within the water column) and benthic dives. In contrast, sea lions that used a deep-diving foraging strategy all had similar values of at-sea FMR that were unrelated to diving behavior. Energy intake did not differ between foraging strategies and was unrelated to energy expenditure. Our findings suggest that energy expenditure in California sea lions may be influenced by interactions between diet and oxygen conservation strategies. There were no apparent energetic trade-offs between foraging strategies, although there was preliminary evidence that foraging strategies may differ in their variability in energy balance. The energetic consequences of behavioral variation may influence the reproductive success of female sea lions and result in differential impacts of individuals on prey populations. These findings highlight the importance of quantifying the relationships between energy expenditure and foraging behavior in other carnivores for studies addressing fundamental and applied physiological and ecological questions.}, } @article {pmid29721301, year = {2018}, author = {Caballero Ortiz, S and Trienens, M and Pfohl, K and Karlovsky, P and Holighaus, G and Rohlfs, M}, title = {Phenotypic responses to microbial volatiles render a mold fungus more susceptible to insect damage.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4328-4339}, pmid = {29721301}, issn = {2045-7758}, abstract = {In decomposer systems, fungi show diverse phenotypic responses to volatile organic compounds of microbial origin (volatiles). The mechanisms underlying such responses and their consequences for the performance and ecological success of fungi in a multitrophic community context have rarely been tested explicitly. We used a laboratory-based approach in which we investigated a tripartite yeast-mold-insect model decomposer system to understand the possible influence of yeast-borne volatiles on the ability of a chemically defended mold fungus to resist insect damage. The volatile-exposed mold phenotype (1) did not exhibit protein kinase A-dependent morphological differentiation, (2) was more susceptible to insect foraging activity, and (3) had reduced insecticidal properties. Additionally, the volatile-exposed phenotype was strongly impaired in secondary metabolite formation and unable to activate "chemical defense" genes upon insect damage. These results suggest that volatiles can be ecologically important factors that affect the chemical-based combative abilities of fungi against insect antagonists and, consequently, the structure and dynamics of decomposer communities.}, } @article {pmid29721300, year = {2018}, author = {Calkins, TL and Chen, ME and Arora, AK and Hawkings, C and Tamborindeguy, C and Pietrantonio, PV}, title = {Brain gene expression analyses in virgin and mated queens of fire ants reveal mating-independent and socially regulated changes.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4312-4327}, pmid = {29721300}, issn = {2045-7758}, abstract = {Transcriptomes of dissected brains from virgin alate and dealate mated queens from polygyne fire ants (Solenopsis invicta) were analyzed and compared. Thirteen genes were upregulated in mated queen brain, and nine were downregulated. While many of the regulated genes were either uncharacterized or noncoding RNAs, those annotated genes included two hexamerin proteins, astakine neuropeptide, serine proteases, and serine protease inhibitors. We found that for select differentially expressed genes in the brain, changes in gene expression were most likely driven by the changes in physiological state (i.e., age, nutritional status, or dominance rank) or in social environment (released from influence of primer pheromone). This was concluded because virgins that dealated after being separated from mated queens showed similar patterns of gene expression in the brain as those of mated queens for hexamerin 1, astakine, and XR_850909. Abaecin (XR_850725), however, appears upregulated only after mating. Therefore, our findings contribute to distinguish how specific gene networks, especially those influenced by queen primer pheromone, are regulated in queen ants. Additionally, to identify brain signaling pathways, we mined the fire ant genome and compiled a list of G-protein-coupled receptors (GPCRs). The expression level of GPCRs and other genes in the "genetic toolkit" in the brains of virgin alates and mated dealate queens is reported.}, } @article {pmid29721299, year = {2018}, author = {Quenta Herrera, E and Casas, J and Dangles, O and Pincebourde, S}, title = {Temperature effects on ballistic prey capture by a dragonfly larva.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4303-4311}, pmid = {29721299}, issn = {2045-7758}, abstract = {Understanding the effects of temperature on prey-predator interactions is a key issue to predict the response of natural communities to climate change. Higher temperatures are expected to induce an increase in predation rates. However, little is known on how temperature influences close-range encounter of prey-predator interactions, such as predator's attack velocities. Based on the speed-accuracy trade-off concept, we hypothesized that the increase in predator attack velocity by increasing temperature reduces the accuracy of the attack, leading to a lower probability of capture. We tested this hypothesis on the dragonfly larvae Anax imperator and the zooplankton prey Daphnia magna. The prey-predator encounters were video-recorded at high speed, and at three different temperatures. Overall, we found that (1) temperature had a strong effect on predator's attack velocities, (2) prey did not have the opportunity to move and/or escape due to the high velocity of the predator during the attack, and (3) neither velocity nor temperature had significant effects on the capture success. By contrast, the capture success mainly depended on the accuracy of the predator in capturing the prey. We found that (4) some 40% of mistakes were undershooting and some 60% aimed below or above the target. No lateral mistake was observed. These results did not support the speed-accuracy trade-off hypothesis. Further studies on dragonfly larvae with different morphological labial masks and speeds of attacks, as well as on prey with different escape strategies, would provide new insights into the response to environmental changes in prey-predator interactions.}, } @article {pmid29721298, year = {2018}, author = {Pardew, J and Blanco Pimentel, M and Low-Decarie, E}, title = {Predictable ecological response to rising CO2 of a community of marine phytoplankton.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4292-4302}, pmid = {29721298}, issn = {2045-7758}, abstract = {Rising atmospheric CO 2 and ocean acidification are fundamentally altering conditions for life of all marine organisms, including phytoplankton. Differences in CO 2 related physiology between major phytoplankton taxa lead to differences in their ability to take up and utilize CO 2. These differences may cause predictable shifts in the composition of marine phytoplankton communities in response to rising atmospheric CO 2. We report an experiment in which seven species of marine phytoplankton, belonging to four major taxonomic groups (cyanobacteria, chlorophytes, diatoms, and coccolithophores), were grown at both ambient (500 μatm) and future (1,000 μatm) CO 2 levels. These phytoplankton were grown as individual species, as cultures of pairs of species and as a community assemblage of all seven species in two culture regimes (high-nitrogen batch cultures and lower-nitrogen semicontinuous cultures, although not under nitrogen limitation). All phytoplankton species tested in this study increased their growth rates under elevated CO 2 independent of the culture regime. We also find that, despite species-specific variation in growth response to high CO 2, the identity of major taxonomic groups provides a good prediction of changes in population growth and competitive ability under high CO 2. The CO 2-induced growth response is a good predictor of CO 2-induced changes in competition (R2 > .93) and community composition (R2 > .73). This study suggests that it may be possible to infer how marine phytoplankton communities respond to rising CO 2 levels from the knowledge of the physiology of major taxonomic groups, but that these predictions may require further characterization of these traits across a diversity of growth conditions. These findings must be validated in the context of limitation by other nutrients. Also, in natural communities of phytoplankton, numerous other factors that may all respond to changes in CO2, including nitrogen fixation, grazing, and variation in the limiting resource will likely complicate this prediction.}, } @article {pmid29721297, year = {2018}, author = {Penjor, U and Macdonald, DW and Wangchuk, S and Tandin, T and Tan, CKW}, title = {Identifying important conservation areas for the clouded leopard Neofelis nebulosa in a mountainous landscape: Inference from spatial modeling techniques.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4278-4291}, pmid = {29721297}, issn = {2045-7758}, abstract = {The survival of large carnivores is increasingly precarious due to extensive human development that causes the habitat loss and fragmentation. Habitat selection is influenced by anthropogenic as well as environmental factors, and understanding these relationships is important for conservation management. We assessed the environmental and anthropogenic variables that influence site use of clouded leopard Neofelis nebulosa in Bhutan, estimated their population density, and used the results to predict the species' site use across Bhutan. We used a large camera-trap dataset from the national tiger survey to estimate for clouded leopards, for the first time in Bhutan, (1) population density using spatially explicit capture-recapture models and (2) site-use probability using occupancy models accounting for spatial autocorrelation. Population density was estimated at D^Bayesian=0.40 (0.10 SD) and D^maximum-likelihood=0.30 (0.12 SE) per 100 km2. Clouded leopard site use was positively associated with forest cover and distance to river while negatively associated with elevation. Mean site-use probability (from the Bayesian spatial model) was ψ^spatial=0.448 (0.076 SD). When spatial autocorrelation was ignored, the probability of site use was overestimated, ψ^nonspatial=0.826 (0.066 SD). Predictive mapping allowed us to identify important conservation areas and priority habitats to sustain the future of these elusive, ambassador felids and associated guilds. Multiple sites in the south, many of them outside of protected areas, were identified as habitats suitable for this species, adding evidence to conservation planning for clouded leopards in continental South Asia.}, } @article {pmid29721296, year = {2018}, author = {Luttikhuizen, PC and van den Heuvel, FHM and Rebours, C and Witte, HJ and van Bleijswijk, JDL and Timmermans, K}, title = {Strong population structure but no equilibrium yet: Genetic connectivity and phylogeography in the kelp Saccharina latissima (Laminariales, Phaeophyta).}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4265-4277}, pmid = {29721296}, issn = {2045-7758}, abstract = {Kelp aquaculture is globally developing steadily as human food source, along with other applications. One of the newer crop species is Saccharina latissima, a northern hemisphere kelp inhabiting temperate to arctic rocky shores. To protect and document its natural genetic variation at the onset of this novel aquaculture, as well as increase knowledge on its taxonomy and phylogeography, we collected new genetic data, both nuclear and mitochondrial, and combined it with previous knowledge to estimate genetic connectivity and infer colonization history. Isolation-with-migration coalescent analyses demonstrate that gene flow among the sampled locations is virtually nonexistent. An updated scenario for the origin and colonization history of S. latissima is developed as follows: We propose that the species (or species complex) originated in the northwest Pacific, crossed to the northeast Pacific in the Miocene, and then crossed the Bering Strait after its opening ~5.5 Ma into the Arctic and northeast Atlantic. It subsequently crossed the Atlantic from east to west. During the Pleistocene, it was compressed in the south with evidence for northern refugia in Europe. Postglacial recolonization led to secondary contact in the Canadian Arctic. Saccharina cichorioides is shown to probably belong to the S. latissima species complex and to derive from ancestral populations in the Asian North Pacific. Our novel approach of comparing inferred gene flow based on coalescent analysis versus Wright's island model suggests that equilibrium levels of differentiation have not yet been reached in Europe and, hence, that genetic differentiation is expected to increase further if populations are left undisturbed.}, } @article {pmid29721295, year = {2018}, author = {Wang, Y and Hodgkinson, KC and Hou, F and Wang, Z and Chang, S}, title = {An evaluation of government-recommended stocking systems for sustaining pastoral businesses and ecosystems of the Alpine Meadows of the Qinghai-Tibetan Plateau.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4252-4264}, pmid = {29721295}, issn = {2045-7758}, abstract = {China introduced the "Retire Livestock and Restore Grassland" policy in 2003. It was strengthened in 2011 by additional funding for on-farm structures. On the Qinghai-Tibetan Plateau (QTP), fences were erected, livestock excluded from degraded areas, rotational stocking introduced, nighttime shelters were built, forages grown, and seed sown. However, the effectiveness of these actions and their value to Tibetan herders has been questioned. We conducted a sheep stocking experiment for 5 years in an Alpine Meadow region of the QTP to evaluate stocking options recommended by Government. Cold and warm season stocking each at three rates (0, 8, and 16 sheep/ha) and continuous stocking at 0 and 4 sheep/ha were compared. We measured live weights of sheep, plant species richness and evenness, root biomass and carbon (C), nitrogen (N) and phosphorus (P) contents of the 0-10 cm of soil. We found that resting grassland from stocking during the warm season for later cold season stocking significantly reduced plant species richness and evenness and root biomass but not soil C, N, and P. During cold season stocking, live weights of sheep declined whether at a stocking rate of 8 or 16 per ha. In contrast, sheep continuously stocked on grassland at 4 per ha gained weight throughout both the warm and cold seasons and plant species richness and evenness were maintained. Warm season stocking at 8 and 16 sheep/ha increased plant species richness and root biomass but reduced plant species evenness. Resting these alpine grasslands from stocking in the warm season has adverse consequences for plant conservation. Fencing from stocking in the warm season is not justified by this study; all grassland should be judiciously stocked during the warm season to maintain plant species richness. Neither resting nor stocking during the cold season appears to have any adverse consequences but sheltering and in-door feeding of sheep during the cold season may be more profitable than cold season stocking with use of open nighttime yards.}, } @article {pmid29721294, year = {2018}, author = {Campbell, MJ and Edwards, W and Magrach, A and Alamgir, M and Porolak, G and Mohandass, D and Laurance, WF}, title = {Edge disturbance drives liana abundance increase and alteration of liana-host tree interactions in tropical forest fragments.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4237-4251}, pmid = {29721294}, issn = {2045-7758}, abstract = {Closed-canopy forests are being rapidly fragmented across much of the tropical world. Determining the impacts of fragmentation on ecological processes enables better forest management and improves species-conservation outcomes. Lianas are an integral part of tropical forests but can have detrimental and potentially complex interactions with their host trees. These effects can include reduced tree growth and fecundity, elevated tree mortality, alterations in tree-species composition, degradation of forest succession, and a substantial decline in forest carbon storage. We examined the individual impacts of fragmentation and edge effects (0-100-m transect from edge to forest interior) on the liana community and liana-host tree interactions in rainforests of the Atherton Tableland in north Queensland, Australia. We compared the liana and tree community, the traits of liana-infested trees, and determinants of the rates of tree infestation within five forest fragments (23-58 ha in area) and five nearby intact-forest sites. Fragmented forests experienced considerable disturbance-induced degradation at their edges, resulting in a significant increase in liana abundance. This effect penetrated to significantly greater depths in forest fragments than in intact forests. The composition of the liana community in terms of climbing guilds was significantly different between fragmented and intact forests, likely because forest edges had more small-sized trees favoring particular liana guilds which preferentially use these for climbing trellises. Sites that had higher liana abundances also exhibited higher infestation rates of trees, as did sites with the largest lianas. However, large lianas were associated with low-disturbance forest sites. Our study shows that edge disturbance of forest fragments significantly altered the abundance and community composition of lianas and their ecological relationships with trees, with liana impacts on trees being elevated in fragments relative to intact forests. Consequently, effective control of lianas in forest fragments requires management practices which directly focus on minimizing forest edge disturbance.}, } @article {pmid29721293, year = {2018}, author = {Ssali, F and Moe, SR and Sheil, D}, title = {Tree seed rain and seed removal, but not the seed bank, impede forest recovery in bracken (Pteridium aquilinum (L.) Kuhn)-dominated clearings in the African highlands.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4224-4236}, pmid = {29721293}, issn = {2045-7758}, abstract = {Considerable areas dominated by bracken Pteridium aquilinum (L.) Kuhn occur worldwide and are associated with arrested forest recovery. How forest recovery is impeded in these areas remains poorly understood, especially in the African highlands. The component processes that can lead to recruitment limitation-including low seed arrival, availability and persistence-are important determinants of plant communities and offer a potential explanation for bracken persistence. We investigated key processes that can contribute to recruitment limitation in bracken-dominated clearings in the Bwindi Impenetrable National Park, Uganda. We examined if differences in seed rain (dispersal limitation), soil seed bank, or seed removal (seed viability and persistence) can, individually or in combination, explain the differences in tree regeneration found between bracken-dominated areas and the neighboring forest. These processes were assessed along ten 50-m transects crossing the forest-bracken boundary. When compared to the neighboring forest, bracken clearings had fewer seedlings (bracken 11,557 ± 5482 vs. forest 34,515 ± 6066 seedlings/ha), lower seed rain (949 ± 582 vs. 1605 ± 335 tree seeds m-2 year-1), comparable but sparse soil seed bank (304 ± 236 vs. 264 ± 99 viable tree seeds/m2), higher seed removal (70.1% ± 2.4% vs. 40.6% ± 2.4% over a 3-day interval), and markedly higher rodent densities (25.7 ± 5.4 vs. 5.0 ± 1.6 rodents per 100 trapping sessions). Camera traps revealed that rodents were the dominant animals visiting the seeds in our seed removal study. Synthesis: Recruitment limitation contributes to both the slow recovery of forest in bracken-dominated areas, and to the composition of the tree species that occur. Low seed arrival and low persistence of unburied seeds can both explain the reduced density of seedlings found in bracken versus neighboring forest. Seed removal, likely due to rodents, in particular appears sufficient to constrain forest recovery and impacts some species more severely than others.}, } @article {pmid29721292, year = {2018}, author = {Lembrechts, JJ and Rossi, E and Milbau, A and Nijs, I}, title = {Habitat properties and plant traits interact as drivers of non-native plant species' seed production at the local scale.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4209-4223}, pmid = {29721292}, issn = {2045-7758}, abstract = {To answer the long-standing question if we can predict plant invader success based on characteristics of the environment (invasibility) or the invasive species (invasiveness), or the combination of both, there is a need for detailed observational studies in which habitat properties, non-native plant traits, and the resulting invader success are locally measured. In this study, we assess the interaction of gradients in the environmental and trait space on non-native species fitness, expressed as seed production, for a set of 10 invasive and noninvasive non-native species along a wide range of invaded sites in Flanders. In our multidimensional approach, most of the single environmental gradients (temperature, light availability, native plant species diversity, and soil fertility) and sets of non-native plant traits (plant size, photosynthesis, and foliar chemical attributes) related positively with invader seed production. Yet correlation with seed production was much stronger when several environmental gradients were assessed in interaction, and even more so when we combined plant traits and habitat properties. The latter increased explanatory power of the models on average by 25% for invasive and by 7% for noninvasive species. Additionally, we report a 70-fold higher seed production in invasive than in noninvasive species and fundamentally different correlations of seed production with plant traits and habitat properties in noninvasive versus invasive species. We conclude that locally measured traits and properties deserve much more attention than they currently get in invasion literature and thus encourage further studies combining this level of detail with the generality of a multiregion and multispecies approach across different stages of invasion.}, } @article {pmid29721291, year = {2018}, author = {Kirk, DA and Park, AC and Smith, AC and Howes, BJ and Prouse, BK and Kyssa, NG and Fairhurst, EN and Prior, KA}, title = {Our use, misuse, and abandonment of a concept: Whither habitat?.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4197-4208}, pmid = {29721291}, issn = {2045-7758}, abstract = {The foundational concept of habitat lies at the very root of the entire science of ecology, but inaccurate use of the term compromises scientific rigor and communication among scientists and nonscientists. In 1997, Hall, Krausman & Morrison showed that 'habitat' was used correctly in only 55% of articles. We ask whether use of the term has been more accurate since their plea for standardization and whether use varies across the broader range of journals and taxa in the contemporary literature (1998-2012). We searched contemporary literature for 'habitat' and habitat-related terms, ranking usage as either correct or incorrect, following a simplified version of Hall et al.'s definitions. We used generalized linear models to compare use of the term in contemporary literature with the papers reviewed by Hall et al. and to test the effects of taxa, journal impact in the contemporary articles and effects due to authors that cited Hall et al. Use of the term 'habitat' has not improved; it was still only used correctly about 55% of the time in the contemporary data. Proportionately more correct uses occurred in articles that focused on animals compared to ones that included plants, and papers that cited Hall et al. did use the term correctly more often. However, journal impact had no effect. Some habitat terms are more likely to be misused than others, notably 'habitat type', usually used to refer to vegetation type, and 'suitable habitat' or 'unsuitable habitat', which are either redundant or nonsensical by definition. Inaccurate and inconsistent use of the term can lead to (1) misinterpretation of scientific findings; (2) inefficient use of conservation resources; (3) ineffective identification and prioritization of protected areas; (4) limited comparability among studies; and (5) miscommunication of science-based findings. Correct usage would improve communication with scientists and nonscientists, thereby benefiting conservation efforts, and ecology as a science.}, } @article {pmid29721290, year = {2018}, author = {Krizsan, SJ and Mateos-Rivera, A and Bertilsson, S and Felton, A and Anttila, A and Ramin, M and Vaga, M and Gidlund, H and Huhtanen, P}, title = {An in vitro evaluation of browser and grazer fermentation efficiency and microbiota using European moose spring and summer foods.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4183-4196}, pmid = {29721290}, issn = {2045-7758}, abstract = {Evolutionary morphological and physiological differences between browsers and grazers contribute to species-specific digestion efficiency of food resources. Rumen microbial community structure of browsers is supposedly adapted to characteristic nutrient composition of the diet source. If this assumption is correct, domesticated ruminants, or grazers, are poor model animals for assessing the nutritional value of food consumed by browsing game species. In this study, typical spring and summer foods of the European moose (Alces alces) were combined with rumen fluid collected from both dairy cows (Bos taurus) and from moose, with the aim of comparing fermentation efficiency and microbial community composition. The nutritional value of the food resources was characterized by chemical analysis and advanced in vitro measurements. The study also addressed whether or not feed evaluation based on in vitro techniques with cattle rumen fluid as inoculum could be a practical alternative when evaluating the nutritional value of plants consumed by wild browsers. Our results suggest that the fermentation characteristics of moose spring and summer food are partly host-specific and related to the contribution of the bacterial phyla Firmicutes and Bacteriodetes to the rumen microbial community. Host-specific adaptations of the ruminal microbial community structure could be explained from the evolutionary adaptations related to feeding habitats and morphophysiological differences between browsers and grazers. However, the observed overall differences in microbial community structure could not be related to ruminal digestion parameters measured in vitro. The in vitro evaluation of digestion efficiency reveals that equal amounts of methane were produced across all feed samples regardless of whether the ruminal fluid was from moose or dairy cow. The results of this study suggested that the nutritional value of browsers' spring and summer food can be predicted using rumen fluid from domesticated grazers as inoculum in in vitro assessments of extent of digestion when excluding samples of the white water lily root, but not of fermentation characteristics as indicated by the proportions of individual fermentation fatty acids to the total of volatile fatty acids.}, } @article {pmid29721289, year = {2018}, author = {Xie, JY and Tang, WJ and Yang, YH}, title = {Fish assemblage changes over half a century in the Yellow River, China.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4173-4182}, pmid = {29721289}, issn = {2045-7758}, abstract = {Riverine environments have been threatened by anthropogenic perturbations worldwide, whereby their fish assemblages have been modified by habitat changes and nonendemic species invasions. We assessed changes in fish assemblages by comparing the species presence in historical and contemporary fish data in the Yellow River from 1965 to 2015. The temporal change in species assemblages was found with increased nonendemic species and fewer natives. Fish species richness of the river declined 35.4% over the past fifty years. Moreover, the decreased mean Bray-Curtis dissimilarity among reaches suggested that the fish assemblages of different reaches in the Yellow River were becoming more similar over time. However, temporal patterns of fish assemblages varied among reaches. In the upper Yellow River, higher species richness and more invasive species were found than those in the historical record, while the lower reaches experienced significant species loss. Dam constructions, exotic fish invasions, and flow reductions played the vital role in structuring the temporal fish assemblages in the Yellow River. It is suggested that river basins which experienced different types and levels of stressors by anthropogenic perturbations can produce varied effects on their temporal trends of species assemblages.}, } @article {pmid29721288, year = {2018}, author = {Shaner, PL and Yu, AY and Li, SH and Hou, CH}, title = {The effects of food and parasitism on reproductive performance of a wild rodent.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4162-4172}, pmid = {29721288}, issn = {2045-7758}, abstract = {Food and parasitism can have complex effects on small mammal reproduction. In this study, we tested the effects of sex, food, and parasitism on reproductive performance of the Taiwan field mouse (Apodemus semotus). In a field experiment, we increased food availability for a portion of the mice in the population by providing sorghum seeds to a set of food stations. We reduced parasite intensity of randomly chosen mice through ivermectin treatment. We determined the number and quality of offspring for the mice using paternity analysis. We quantified seed consumption with stable carbon isotope values of mouse plasma and parasite intensity with fecal egg counts of intestinal nematodes and cestodes (FEC). In a laboratory experiment, we reduced parasite intensity of randomly chosen mice through ivermectin treatment. We quantified their immune functions by total white blood cell count, percent granulocyte count, and percent lymphocyte count through hematological analyses. We measured the FEC and energy intake of the mice. From the field experiment, the number of offspring in A. semotus increased with increasing seed consumption. Due to the trade-off between number and quality of offspring, the offspring quality decreased with increasing seed consumption for the females. The ivermectin treatment did not affect offspring number or quality. However, the FEC was positively correlated with number of offspring. In the laboratory experiment, the percent lymphocyte/granulocyte count changed with parasite intensity at low energy intake, which was relaxed at high energy intake. This study demonstrated positive effects of food availability and neutral effects of parasitism on A. semotus reproduction. However, the benefits of food availability for the females need to take into account the offspring number-quality trade-off, and at high infection intensity, parasitism might negatively affect offspring quality for the males. We suggest that food availability could mediate the relationships between parasite intensity and immune responses.}, } @article {pmid29721287, year = {2018}, author = {Heys, C and Lizé, A and Blow, F and White, L and Darby, A and Lewis, ZJ}, title = {The effect of gut microbiota elimination in Drosophila melanogaster: A how-to guide for host-microbiota studies.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4150-4161}, pmid = {29721287}, issn = {2045-7758}, abstract = {In recent years, there has been a surge in interest in the effects of the microbiota on the host. Increasingly, we are coming to understand the importance of the gut microbiota in modulating host physiology, ecology, behavior, and evolution. One method utilized to evaluate the effect of the microbiota is to suppress or eliminate it, and compare the effect on the host with that of untreated individuals. In this study, we evaluate some of these commonly used methods in the model organism, Drosophila melanogaster. We test the efficacy of a low-dose streptomycin diet, egg dechorionation, and an axenic or sterile diet, in the removal of gut bacteria within this species in a fully factorial design. We further determine potential side effects of these methods on host physiology by performing a series of standard physiological assays. Our results showed that individuals from all treatments took significantly longer to develop, and weighed less, compared to normal flies. Males and females that had undergone egg dechorionation weighed significantly less than streptomycin reared individuals. Similarly, axenic female flies, but not males, were much less active when analyzed in a locomotion assay. All methods decreased the egg to adult survival, with egg dechorionation inducing significantly higher mortality. We conclude that low-dose streptomycin added to the dietary media is more effective at removing the gut bacteria than egg dechorionation and has somewhat less detrimental effects to host physiology. More importantly, this method is the most practical and reliable for use in behavioral research. Our study raises the important issue that the efficacy of and impacts on the host of these methods require investigation in a case-by-case manner, rather than assuming homogeneity across species and laboratories.}, } @article {pmid29721286, year = {2018}, author = {von Oheimb, PV and von Oheimb, KCM and Hirano, T and Do, TV and Luong, HV and Ablett, J and Pham, SV and Naggs, F}, title = {Competition matters: Determining the drivers of land snail community assembly among limestone karst areas in northern Vietnam.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4136-4149}, pmid = {29721286}, issn = {2045-7758}, abstract = {The insular limestone karsts of northern Vietnam harbor a very rich biodiversity. Many taxa are strongly associated with these environments, and individual species communities can differ considerably among karst areas. The exact processes that have shaped the biotic composition of these habitats, however, remain largely unknown. In this study, the role of two major processes for the assembly of snail communities on limestone karsts was investigated, interspecific competition and filtering of taxa due to geographical factors. Communities of operculate land snails of the genus Cyclophorus were studied using the dry and fluid-preserved specimen collections of the Natural History Museum, London. Phylogenetic distances (based on a Bayesian analysis using DNA sequence data) and shell characters (based on 200 semilandmarks) were used as proxies for ecological similarity and were analyzed to reveal patterns of overdispersion (indicating competition) or clustering (indicating filtering) in observed communities compared to random communities. Among the seven studied karst areas, a total of 15 Cyclophorus lineages were found. Unique communities were present in each area. The analyses revealed phylogenetic overdispersion in six and morphological overdispersion in four of seven karst areas. The pattern of frequent phylogenetic overdispersion indicated that competition among lineages is the major process shaping the Cyclophorus communities studied. The Coastal Area, which was phylogenetically overdispersed, showed a clear morphological clustering, which could have been caused by similar ecological adaptations among taxa in this environment. Only the community in the Cuc Phuong Area showed a pattern of phylogenetic clustering, which was partly caused by an absence of a certain, phylogenetically very distinct group in this region. Filtering due to geographical factors could have been involved here. This study shows how museum collections can be used to examine community assembly and contributes to the understanding of the processes that have shaped karst communities in Vietnam.}, } @article {pmid29721285, year = {2018}, author = {Baattrup-Pedersen, A and Garssen, A and Göthe, E and Hoffmann, CC and Oddershede, A and Riis, T and van Bodegom, PM and Larsen, SE and Soons, M}, title = {Structural and functional responses of plant communities to climate change-mediated alterations in the hydrology of riparian areas in temperate Europe.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4120-4135}, pmid = {29721285}, issn = {2045-7758}, abstract = {The hydrology of riparian areas changes rapidly these years because of climate change-mediated alterations in precipitation patterns. In this study, we used a large-scale in situ experimental approach to explore effects of drought and flooding on plant taxonomic diversity and functional trait composition in riparian areas in temperate Europe. We found significant effects of flooding and drought in all study areas, the effects being most pronounced under flooded conditions. In near-stream areas, taxonomic diversity initially declined in response to both drought and flooding (although not significantly so in all years) and remained stable under drought conditions, whereas the decline continued under flooded conditions. For most traits, we found clear indications that the functional diversity also declined under flooded conditions, particularly in near-stream areas, indicating that fewer strategies succeeded under flooded conditions. Consistent changes in community mean trait values were also identified, but fewer than expected. This can have several, not mutually exclusive, explanations. First, different adaptive strategies may coexist in a community. Second, intraspecific variability was not considered for any of the traits. For example, many species can elongate shoots and petioles that enable them to survive shallow, prolonged flooding but such abilities will not be captured when applying mean trait values. Third, we only followed the communities for 3 years. Flooding excludes species intolerant of the altered hydrology, whereas the establishment of new species relies on time-dependent processes, for instance the dispersal and establishment of species within the areas. We expect that altered precipitation patterns will have profound consequences for riparian vegetation in temperate Europe. Riparian areas will experience loss of taxonomic and functional diversity and, over time, possibly also alterations in community trait responses that may have cascading effects on ecosystem functioning.}, } @article {pmid29721284, year = {2018}, author = {Bellwood, DR and Tebbett, SB and Bellwood, O and Mihalitsis, M and Morais, RA and Streit, RP and Fulton, CJ}, title = {The role of the reef flat in coral reef trophodynamics: Past, present, and future.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4108-4119}, pmid = {29721284}, issn = {2045-7758}, abstract = {The reef flat is one of the largest and most distinctive habitats on coral reefs, yet its role in reef trophodynamics is poorly understood. Evolutionary evidence suggests that reef flat colonization by grazing fishes was a major innovation that permitted the exploitation of new space and trophic resources. However, the reef flat is hydrodynamically challenging, subject to high predation risks and covered with sediments that inhibit feeding by grazers. To explore these opposing influences, we examine the Great Barrier Reef (GBR) as a model system. We focus on grazing herbivores that directly access algal primary productivity in the epilithic algal matrix (EAM). By assessing abundance, biomass, and potential fish productivity, we explore the potential of the reef flat to support key ecosystem processes and its ability to maintain fisheries yields. On the GBR, the reef flat is, by far, the most important habitat for turf-grazing fishes, supporting an estimated 79% of individuals and 58% of the total biomass of grazing surgeonfishes, parrotfishes, and rabbitfishes. Approximately 59% of all (reef-wide) turf algal productivity is removed by reef flat grazers. The flat also supports approximately 75% of all grazer biomass growth. Our results highlight the evolutionary and ecological benefits of occupying shallow-water habitats (permitting a ninefold population increase). The acquisition of key locomotor and feeding traits has enabled fishes to access the trophic benefits of the reef flat, outweighing the costs imposed by water movement, predation, and sediments. Benthic assemblages on reefs in the future may increasingly resemble those seen on reef flats today, with low coral cover, limited topographic complexity, and extensive EAM. Reef flat grazing fishes may therefore play an increasingly important role in key ecosystem processes and in sustaining future fisheries yields.}, } @article {pmid29721283, year = {2018}, author = {Head, CEI and Koldewey, H and Pavoine, S and Pratchett, MS and Rogers, AD and Taylor, ML and Bonsall, MB}, title = {Trait and phylogenetic diversity provide insights into community assembly of reef-associated shrimps (Palaemonidae) at different spatial scales across the Chagos Archipelago.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4098-4107}, pmid = {29721283}, issn = {2045-7758}, abstract = {Coral reefs are the most biodiverse marine ecosystem and one of the most threatened by global climate change impacts. The vast majority of diversity on reefs is comprised of small invertebrates that live within the reef structure, termed the cryptofauna. This component of biodiversity is hugely understudied, and many species remain undescribed. This study represents a rare analysis of assembly processes structuring a distinct group of cryptofauna, the Palaemonidae, in the Chagos Archipelago, a reef ecosystem under minimal direct human impacts in the central Indian Ocean. The Palaemonidae are a diverse group of Caridae (infraorder of shrimps) that inhabit many different niches on coral reefs and are of particular interest because of their varied habitat associations. Phylogenetic and trait diversity and phylogenetic signal were used to infer likely drivers of community structure. The mechanisms driving palaemonid community assembly and maintenance in the Chagos Archipelago showed distinct spatial patterns. At local scales, among coral colonies and among reefs fringing individual atolls, significant trait, and phylogenetic clustering patterns suggest environmental filtering may be a dominant ecological process driving Palaemonidae community structure, although local competition through equalizing mechanisms may also play a role in shaping the local community structure. Importantly, we also tested the robustness of phylogenetic diversity to changes in evolutionary information as multi-gene phylogenies are resource intensive and for large families, such as the Palaemonidae, are often incomplete. These tests demonstrated a very modest impact on phylogenetic community structure, with only one of the four genes (PEPCK gene) in the phylogeny affecting phylogenetic diversity patterns, which provides useful information for future studies on large families with incomplete phylogenies. These findings contribute to our limited knowledge of this component of biodiversity in a marine locality as close to undisturbed by humans as can be found. It also provides a rare evaluation of phylogenetic diversity methods.}, } @article {pmid29721282, year = {2018}, author = {Brown, EB and Torres, J and Bennick, RA and Rozzo, V and Kerbs, A and DiAngelo, JR and Keene, AC}, title = {Variation in sleep and metabolic function is associated with latitude and average temperature in Drosophila melanogaster.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4084-4097}, pmid = {29721282}, issn = {2045-7758}, support = {R01 NS085152/NS/NINDS NIH HHS/United States ; }, abstract = {Regulation of sleep and metabolic homeostasis is critical to an animal's survival and under stringent evolutionary pressure. Animals display remarkable diversity in sleep and metabolic phenotypes; however, an understanding of the ecological forces that select for, and maintain, these phenotypic differences remains poorly understood. The fruit fly, Drosophila melanogaster, is a powerful model for investigating the genetic regulation of sleep and metabolic function, and screening in inbred fly lines has led to the identification of novel genetic regulators of sleep. Nevertheless, little is known about the contributions of naturally occurring genetic differences to sleep, metabolic phenotypes, and their relationship with geographic or environmental gradients. Here, we quantified sleep and metabolic phenotypes in 24 D. melanogaster populations collected from diverse geographic localities. These studies reveal remarkable variation in sleep, starvation resistance, and energy stores. We found that increased sleep duration is associated with proximity to the equator and elevated average annual temperature, suggesting that environmental gradients strongly influence natural variation in sleep. Further, we found variation in metabolic regulation of sleep to be associated with free glucose levels, while starvation resistance associates with glycogen and triglyceride stores. Taken together, these findings reveal robust naturally occurring variation in sleep and metabolic traits in D. melanogaster, providing a model to investigate how evolutionary and ecological history modulate these complex traits.}, } @article {pmid29721281, year = {2018}, author = {Ostfeld, RS and Brisson, D and Oggenfuss, K and Devine, J and Levy, MZ and Keesing, F}, title = {Effects of a zoonotic pathogen, Borrelia burgdorferi, on the behavior of a key reservoir host.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4074-4083}, pmid = {29721281}, issn = {2045-7758}, abstract = {Most emerging infectious diseases of humans are transmitted to humans from other animals. The transmission of these "zoonotic" pathogens is affected by the abundance and behavior of their wildlife hosts. However, the effects of infection with zoonotic pathogens on behavior of wildlife hosts, particularly those that might propagate through ecological communities, are not well understood. Borrelia burgdorferi is a bacterium that causes Lyme disease, the most common vector-borne disease in the USA and Europe. In its North American range, the pathogen is most frequently transmitted among hosts through the bite of infected blacklegged ticks (Ixodes scapularis). Using sham and true vaccines, we experimentally manipulated infection load with this zoonotic pathogen in its most competent wildlife reservoir host, the white-footed mouse, Peromyscus leucopus, and quantified the effects of infection on mouse foraging behavior, as well as levels of mouse infestation with ticks. Mice treated with the true vaccine had 20% fewer larval blacklegged ticks infesting them compared to mice treated with the sham vaccine, a significant difference. We observed a nonsignificant trend for mice treated with the true vaccine to be more likely to visit experimental foraging trays (20%-30% effect size) and to prey on gypsy moth pupae (5%-20% effect size) compared to mice treated with the sham vaccine. We observed no difference between mice on true- versus sham-vaccinated grids in risk-averse foraging. Infection with this zoonotic pathogen appears to elicit behavioral changes that might reduce self-grooming, but other behaviors were affected subtly or not at all. High titers of B. burgdorferi in mice could elicit a self-reinforcing feedback loop in which reduced grooming increases tick burdens and hence exposure to tick-borne pathogens.}, } @article {pmid29721280, year = {2018}, author = {Nilsson, ALK and L'Abée-Lund, JH and Vøllestad, LA and Jerstad, K and Larsen, BM and Røstad, OW and Saltveit, SJ and Skaugen, T and Stenseth, NC and Walseng, B}, title = {The potential influence of Atlantic salmon Salmo salar and brown trout Salmo trutta on density and breeding of the white-throated dipper Cinclus cinclus.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4065-4073}, pmid = {29721280}, issn = {2045-7758}, abstract = {Interactions between birds and fish are often overlooked in aquatic ecosystems. We studied the influence of Atlantic salmon and brown trout on the breeding population size and reproductive output of the white-throated dipper in a Norwegian river. Acidic precipitation led to the extinction of salmon, but salmon recolonized after liming was initiated in 1991. We compared the dipper population size and reproductive output before (1978-1992) and after (1993-2014) salmon recolonization. Despite a rapid and substantial increase in juvenile salmon, the breeding dipper population size and reproductive output were not influenced by juvenile salmon, trout, or total salmonid density. This might be due to different feeding strategies in salmonids and dippers, where salmonids are mainly feeding on drift, while the dipper is a benthic feeder. The correlation between the size of the dipper population upstream and downstream of a salmonid migratory barrier was similar before and after recolonization, indicating that the downstream territories were not less attractive after the recolonization of salmon. Upstream dipper breeding success rates declined before the recolonization event and increased after, indicating improved water quality due to liming, and increasing invertebrate prey abundances and biodiversity. Surprisingly, upstream the migratory barrier, juvenile trout had a weak positive effect on the dipper population size, indicating that dippers may prey upon small trout. It is possible that wider downstream reaches might have higher abundances of alternative food, rending juvenile trout unimportant as prey. Abiotic factors such as winter temperatures and acidic precipitation with subsequent liming, potentially mediated by prey abundance, seem to play the most important role in the life history of the dipper.}, } @article {pmid29721279, year = {2018}, author = {King, SRB and Schoenecker, KA and Fike, JA and Oyler-McCance, SJ}, title = {Long-term persistence of horse fecal DNA in the environment makes equids particularly good candidates for noninvasive sampling.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4053-4064}, pmid = {29721279}, issn = {2045-7758}, abstract = {Fecal DNA collected noninvasively can provide valuable information about genetic and ecological characteristics. This approach has rarely been used for equids, despite the need for conservation of endangered species and management of abundant feral populations. We examined factors affecting the efficacy of using equid fecal samples for conservation genetics. First, we evaluated two fecal collection methods (paper bag vs. ethanol). Then, we investigated how time since deposition and month of collection impacted microsatellite amplification success and genotyping errors. Between May and November 2014, we collected feral horse fecal samples of known age each month in a feral horse Herd Management Area in western Colorado and documented deterioration in the field with photographs. Samples collected and dried in paper bags had significantly higher amplification rates than those collected and stored in ethanol. There was little difference in the number of loci that amplified per sample between fresh fecal piles and those that had been exposed to the environment for up to 2 months (in samples collected in paper bags). After 2 months of exposure, amplification success declined. When comparing fresh (0-2 months) and old (3-6 months) fecal piles, samples from fresh piles had more matching genotypes across samples, better amplification success and less allelic dropout. Samples defecated during the summer and collected within 2 months of deposition had highest number of genotypes matching among samples, and lowest rates of amplification failure and allelic dropout. Due to the digestive system and amount of fecal material produced by equids, as well as their occurrence in arid ecosystems, we suggest that they are particularly good candidates for noninvasive sampling using fecal DNA.}, } @article {pmid29721278, year = {2018}, author = {Cove, MV and Gardner, B and Simons, TR and O'Connell, AF}, title = {Co-occurrence dynamics of endangered Lower Keys marsh rabbits and free-ranging domestic cats: Prey responses to an exotic predator removal program.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4042-4052}, pmid = {29721278}, issn = {2045-7758}, abstract = {The Lower Keys marsh rabbit (Sylvilagus palustris hefneri) is one of many endangered endemic species of the Florida Keys. The main threats are habitat loss and fragmentation from sea-level rise, development, and habitat succession. Exotic predators such as free-ranging domestic cats (Felis catus) pose an additional threat to these endangered small mammals. Management strategies have focused on habitat restoration and exotic predator control. However, the effectiveness of predator removal and the effects of anthropogenic habitat modifications and restoration have not been evaluated. Between 2013 and 2015, we used camera traps to survey marsh rabbits and free-ranging cats at 84 sites in the National Key Deer Refuge, Big Pine Key, Florida, USA. We used dynamic occupancy models to determine factors associated with marsh rabbit occurrence, colonization, extinction, and the co-occurrence of marsh rabbits and cats during a period of predator removal. Rabbit occurrence was positively related to freshwater habitat and patch size, but was negatively related to the number of individual cats detected at each site. Furthermore, marsh rabbit colonization was negatively associated with relative increases in the number of individual cats at each site between survey years. Cat occurrence was negatively associated with increasing distance from human developments. The probability of cat site extinction was positively related to a 2-year trapping effort, indicating that predator removal reduced the cat population. Dynamic co-occurrence models suggested that cats and marsh rabbits co-occur less frequently than expected under random conditions, whereas co-detections were site and survey-specific. Rabbit site extinction and colonization were not strongly conditional on cat presence, but corresponded with a negative association. Our results suggest that while rabbits can colonize and persist at sites where cats occur, it is the number of individual cats at a site that more strongly influences rabbit occupancy and colonization. These findings indicate that continued predator management would likely benefit endangered small mammals as they recolonize restored habitats.}, } @article {pmid29721277, year = {2018}, author = {Ergon, R}, title = {The environmental zero-point problem in evolutionary reaction norm modeling.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4031-4041}, pmid = {29721277}, issn = {2045-7758}, abstract = {There is a potential problem in present quantitative genetics evolutionary modeling based on reaction norms. Such models are state-space models, where the multivariate breeder's equation in some form is used as the state equation that propagates the population state forward in time. These models use the implicit assumption of a constant reference environment, in many cases set to zero. This zero-point is often the environment a population is adapted to, that is, where the expected geometric mean fitness is maximized. Such environmental reference values follow from the state of the population system, and they are thus population properties. The environment the population is adapted to, is, in other words, an internal population property, independent of the external environment. It is only when the external environment coincides with the internal reference environment, or vice versa, that the population is adapted to the current environment. This is formally a result of state-space modeling theory, which is an important theoretical basis for evolutionary modeling. The potential zero-point problem is present in all types of reaction norm models, parametrized as well as function-valued, and the problem does not disappear when the reference environment is set to zero. As the environmental reference values are population characteristics, they ought to be modeled as such. Whether such characteristics are evolvable is an open question, but considering the complexity of evolutionary processes, such evolvability cannot be excluded without good arguments. As a straightforward solution, I propose to model the reference values as evolvable mean traits in their own right, in addition to other reaction norm traits. However, solutions based on an evolvable G matrix are also possible.}, } @article {pmid29721276, year = {2018}, author = {Häkkilä, M and Abrego, N and Ovaskainen, O and Mönkkönen, M}, title = {Habitat quality is more important than matrix quality for bird communities in protected areas.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4019-4030}, pmid = {29721276}, issn = {2045-7758}, abstract = {Protected areas are meant to preserve native local communities within their boundaries, but they are not independent from their surroundings. Impoverished habitat quality in the matrix might influence the species composition within the protected areas through biotic homogenization. The aim of this study was to determine the impacts of matrix quality on species richness and trait composition of bird communities from the Finnish reserve area network and whether the communities are being subject of biotic homogenization due to the lowered quality of the landscape matrix. We used joint species distribution modeling to study how characteristics of the Finnish forest reserves and the quality of their surrounding matrix alter species and trait compositions of forest birds. The proportion of old forest within the reserves was the main factor in explaining the bird community composition, and the bird communities within the reserves did not strongly depend on the quality of the matrix. Yet, in line with the homogenization theory, the beta-diversity within reserves embedded in low-quality matrix was lower than that in high-quality matrix, and the average abundance of regionally abundant species was higher. Influence of habitat quality on bird community composition was largely explained by the species' functional traits. Most importantly, the community specialization index was low, and average body size was high in areas with low proportion of old forest. We conclude that for conserving local bird communities in northern Finnish protected forests, it is currently more important to improve or maintain habitat quality within the reserves than in the surrounding matrix. Nevertheless, we found signals of bird community homogenization, and thus, activities that decrease the quality of the matrix are a threat for bird communities.}, } @article {pmid29721275, year = {2018}, author = {Jacob Machado, D and Janies, D and Brouwer, C and Grant, T}, title = {A new strategy to infer circularity applied to four new complete frog mitogenomes.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {4011-4018}, pmid = {29721275}, issn = {2045-7758}, abstract = {We applied a novel strategy to infer sequence circularity and complete assembly of four mitochondrial genomes (mitogenomes) of the frog families Bufonidae (Melanophryniscus moreirae), Dendrobatidae (Hyloxalus subpunctatus and Phyllobates terribilis), and Scaphiopodidae (Scaphiopus holbrookii). These are the first complete mitogenomes of these four genera and Scaphiopodidae. We assembled mitogenomes from short genomic sequence reads using a baiting and iterative mapping strategy followed by a new ad hoc mapping strategy developed to test for assembly circularization. To assess the quality of the inferred circularization, we used Bowtie2 alignment scores and a new per-position sequence coverage value (which we named "connectivity"). Permutation tests with 400 iterations per specimen and 1% or 5% chance of mutation at the ends of the putative circular sequences showed that the proposed method is highly sensitive, with a single nucleotide insertion or deletion being sufficient for circularity to be rejected. False positives comprised only 2% of all observations and possessed significantly lower alignment scores. The size, gene content, and gene arrangement of each mitogenome differed among the species but matched the expectations for their clades. We argue that basic studies on circular sequences can benefit from the results and bioinformatics procedures introduced here, especially when closely related references are lacking.}, } @article {pmid29721274, year = {2018}, author = {Ghitarrini, S and Pierboni, E and Rondini, C and Tedeschini, E and Tovo, GR and Frenguelli, G and Albertini, E}, title = {New biomolecular tools for aerobiological monitoring: Identification of major allergenic Poaceae species through fast real-time PCR.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3996-4010}, pmid = {29721274}, issn = {2045-7758}, abstract = {Grasses (Poaceae) are very common plants, which are widespread in all environments and urban areas. Despite their economical importance, they can represent a problem to humans due to their abundant production of allergenic pollen. Detailed information about the pollen season for these species is needed in order to plan adequate therapies and to warn allergic people about the risks they take in certain areas at certain moments. Moreover, precise identification of the causative species and their allergens is necessary when the patient is treated with allergen-specific immunotherapy. The intrafamily morphological similarity of grass pollen grains makes it impossible to distinguish which particular species is present in the atmosphere at a given moment. This study aimed at developing new biomolecular tools to analyze aerobiological samples and identifying major allergenic Poaceae taxa at subfamily or species level, exploiting fast real-time PCR. Protocols were tested for DNA extraction from pollen sampled with volumetric and gravimetric methods. A fragment of the matK plastidial gene was amplified and sequenced in Poaceae species known to have high allergological impact. Species- and subfamily-specific primer-probe systems were designed and tested in fast real-time PCRs to evaluate the presence of these taxa in aerobiological pollen samples. Species-specific systems were obtained for four of five studied species. A primer-probe set was also proposed for the detection of Pooideae (a grass subfamily that includes also major cereal grains) in aerobiological samples, as this subfamily includes species carrying both grass allergens from groups 1 and 5. These, among the 11 groups in which grass pollen allergens are classified, are considered responsible for the most frequent and severe symptoms.}, } @article {pmid29721273, year = {2018}, author = {Codron, D and Clauss, M and Codron, J and Tütken, T}, title = {Within trophic level shifts in collagen-carbonate stable carbon isotope spacing are propagated by diet and digestive physiology in large mammal herbivores.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3983-3995}, pmid = {29721273}, issn = {2045-7758}, abstract = {Stable carbon isotope analyses of vertebrate hard tissues such as bones, teeth, and tusks provide information about animal diets in ecological, archeological, and paleontological contexts. There is debate about how carbon isotope compositions of collagen and apatite carbonate differ in terms of their relationship to diet, and to each other. We evaluated relationships between δ13Ccollagen and δ13Ccarbonate among free-ranging southern African mammals to test predictions about the influences of dietary and physiological differences between species. Whereas the slopes of δ13Ccollagen-δ13Ccarbonate relationships among carnivores are ≤1, herbivore δ13Ccollagen increases with increasing dietary δ13C at a slower rate than does δ13Ccarbonate, resulting in regression slopes >1. This outcome is consistent with predictions that herbivore δ13Ccollagen is biased against low protein diet components (13C-enriched C4 grasses in these environments), and δ13Ccarbonate is 13C-enriched due to release of 13C-depleted methane as a by-product of microbial fermentation in the digestive tract. As methane emission is constrained by plant secondary metabolites in browse, the latter effect becomes more pronounced with higher levels of C4 grass in the diet. Increases in δ13Ccarbonate are also larger in ruminants than nonruminants. Accordingly, we show that Δ13Ccollagen-carbonate spacing is not constant within herbivores, but increases by up to 5 ‰ across species with different diets and physiologies. Such large variation, often assumed to be negligible within trophic levels, clearly cannot be ignored in carbon isotope-based diet reconstructions.}, } @article {pmid29721272, year = {2018}, author = {Chazot, N and De-Silva, DL and Willmott, KR and Freitas, AVL and Lamas, G and Mallet, J and Giraldo, CE and Uribe, S and Elias, M}, title = {Contrasting patterns of Andean diversification among three diverse clades of Neotropical clearwing butterflies.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3965-3982}, pmid = {29721272}, issn = {2045-7758}, abstract = {The Neotropical region is the most biodiverse on Earth, in a large part due to the highly diverse tropical Andean biota. The Andes are a potentially important driver of diversification within the mountains and for neighboring regions. We compared the role of the Andes in diversification among three subtribes of Ithomiini butterflies endemic to the Neotropics, Dircennina, Oleriina, and Godyridina. The diversification patterns of Godyridina have been studied previously. Here, we generate the first time-calibrated phylogeny for the largest ithomiine subtribe, Dircennina, and we reanalyze a published phylogeny of Oleriina to test different biogeographic scenarios involving the Andes within an identical framework. We found common diversification patterns across the three subtribes, as well as major differences. In Dircennina and Oleriina, our results reveal a congruent pattern of diversification related to the Andes with an Andean origin, which contrasts with the Amazonian origin and multiple Andean colonizations of Godyridina. In each of the three subtribes, a clade diversified in the Northern Andes at a faster rate. Diversification within Amazonia occurred in Oleriina and Godyridina, while virtually no speciation occurred in Dircennina in this region. Dircennina was therefore characterized by higher diversification rates within the Andes compared to non-Andean regions, while in Oleriina and Godyridina, we found no difference between these regions. Our results and discussion highlight the importance of comparative approaches in biogeographic studies.}, } @article {pmid29721271, year = {2018}, author = {Moritsch, MM and Raimondi, PT}, title = {Reduction and recovery of keystone predation pressure after disease-related mass mortality.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3952-3964}, pmid = {29721271}, issn = {2045-7758}, abstract = {Disturbances such as disease can reshape communities through interruption of ecological interactions. Changes to population demographics alter how effectively a species performs its ecological role. While a population may recover in density, this may not translate to recovery of ecological function. In 2013, a sea star wasting syndrome outbreak caused mass mortality of the keystone predator Pisaster ochraceus on the North American Pacific coast. We analyzed sea star counts, biomass, size distributions, and recruitment from long-term intertidal monitoring sites from San Diego to Alaska to assess regional trends in sea star recovery following the outbreak. Recruitment, an indicator of population recovery, has been spatially patchy and varied within and among regions of the coast. Despite sea star counts approaching predisease numbers, sea star biomass, a measure of predation potential on the mussel Mytilus californianus, has remained low. This indicates that post-outbreak populations have not regained their full predation pressure. The regional variability in percent of recovering sites suggested differences in factors promoting sea star recovery between regions but did not show consistent patterns in postoutbreak recruitment on a coast-wide scale. These results shape predictions of where changes in community composition are likely to occur in years following the disease outbreak and provide insight into how populations of keystone species resume their ecological roles following mortality-inducing disturbances.}, } @article {pmid29721270, year = {2018}, author = {Vallant, S and Niederstätter, H and Berger, B and Lentner, R and Parson, W}, title = {Increased DNA typing success for feces and feathers of capercaillie (Tetrao urogallus) and black grouse (Tetrao tetrix).}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3941-3951}, pmid = {29721270}, issn = {2045-7758}, abstract = {Noninvasive sampling, for example, of droppings or feathers, is a promising approach for molecular genetic studies on endangered and elusive animal species. Yet, such specimens are known for containing only minute amounts of DNA, resulting in lower typing success rates relative to analyses on fresh tissues such as muscle or blood. Furthermore, artefactual signals as well as contamination are more likely to occur when DNA is limited. To increase the reliability of DNA typing from noninvasive samples, optimized DNA extraction and polymerase chain reaction protocols were developed, taking advantage of developments in the forensic field aiming at successful molecular genetic analysis of DNA templates being low in quality and quantity. In the framework of an extensive monitoring project on population dynamics of capercaillie and black grouse in the Tyrolean Alps, feces samples and molted feathers from both species were collected. On a subset comprising about 200 specimens of either species, eight polymorphic short tandem repeat (STR) markers were analyzed to test these improved protocols. Besides optimizing DNA yields, both lowered sample consumption and reduced hands-on time were achieved, and the rates of informative profiles amounted to 90.7% for capercaillie and 92.4% for black grouse. Similarly, high success rates had not been achieved in earlier studies and demonstrate the benefit of the improved methodology, which should be easily adaptable for use on animal species other than those studied here. The STR genotypes were not only powerful enough to discriminate among unrelated birds but also appeared fit for telling apart closely related animals, as indicated by Pi and Pisib values. The software package allelematch aided analysis of genotypes featuring possible dropout and drop-in effects. Finally, a comparison between molecular genetic and morphology-based species-of-origin determination revealed a high degree of concordance.}, } @article {pmid29721269, year = {2018}, author = {Hinton, JW and Gittleman, JL and van Manen, FT and Chamberlain, MJ}, title = {Size-assortative choice and mate availability influences hybridization between red wolves (Canis rufus) and coyotes (Canis latrans).}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3927-3940}, pmid = {29721269}, issn = {2045-7758}, abstract = {Anthropogenic hybridization of historically isolated taxa has become a primary conservation challenge for many imperiled species. Indeed, hybridization between red wolves (Canis rufus) and coyotes (Canis latrans) poses a significant challenge to red wolf recovery. We considered seven hypotheses to assess factors influencing hybridization between red wolves and coyotes via pair-bonding between the two species. Because long-term monogamy and defense of all-purpose territories are core characteristics of both species, mate choice has long-term consequences. Therefore, red wolves may choose similar-sized mates to acquire partners that behave similarly to themselves in the use of space and diet. We observed multiple factors influencing breeding pair formation by red wolves and found that most wolves paired with similar-sized conspecifics and wolves that formed congeneric pairs with nonwolves (coyotes and hybrids) were mostly female wolves, the smaller of the two sexes. Additionally, we observed that lower red wolf abundance relative to nonwolves and the absence of helpers increased the probability that wolves consorted with nonwolves. However, successful pairings between red wolves and nonwolves were associated with wolves that maintained small home ranges. Behaviors associated with territoriality are energetically demanding and behaviors (e.g., aggressive interactions, foraging, and space use) involved in maintaining territories are influenced by body size. Consequently, we propose the hypothesis that size disparities between consorting red wolves and coyotes influence positive assortative mating and may represent a reproductive barrier between the two species. We offer that it may be possible to maintain wild populations of red wolves in the presence of coyotes if management strategies increase red wolf abundance on the landscape by mitigating key threats, such as human-caused mortality and hybridization with coyotes. Increasing red wolf abundance would likely restore selection pressures that increase mean body and home-range sizes of red wolves and decrease hybridization rates via reduced occurrence of congeneric pairs.}, } @article {pmid29721268, year = {2018}, author = {Liu, Y and Ma, G and Zan, Z and Chen, A and Miao, Y and Wang, D and Miao, R}, title = {Effects of nitrogen addition and mowing on rodent damage in an Inner Mongolian steppe.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3919-3926}, pmid = {29721268}, issn = {2045-7758}, abstract = {Rodent damage is a serious threat to sustainable management of grassland. The effects of nitrogen (N) deposition and grassland management on rodent damage have been scarcely studied. Here, we reported the effects of 2 years of N addition and mowing on burrow density and damage area of Citellus dauricus in a semiarid steppe in Inner Mongolia. N addition significantly aggravated, while mowing alleviated rodent damage in the grassland under study. Burrow density and damage area increased 2.8-fold and 4.7-fold, in N addition plots compared to the ambient N addition treatment, respectively. Conversely, mowing decreased burrow density and damage area by 75.9% and 14.5%, respectively, compared to no mowing plots. Observed changes in rodent damage were mainly due to variations in plant community cover, height, and aboveground net primary productivity. Our findings demonstrate that N addition and mowing can affect the rodent density and activity in grassland, suggesting that the effects of a changing atmospheric composition and land use on rodent damage must be considered in order to achieve better grassland management.}, } @article {pmid29721267, year = {2018}, author = {Ozawa, S and Hasegawa, K}, title = {Broad infectivity of Leidynema appendiculatum (Nematoda: Oxyurida: Thelastomatidae) parasite of the smokybrown cockroach Periplaneta fuliginosa (Blattodea: Blattidae).}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3908-3918}, pmid = {29721267}, issn = {2045-7758}, abstract = {Host specificity of parasites is important for the understanding of evolutionary strategies of parasitism that would be a basis of predictions of the disease expansion when parasitized hosts invade new environments. The nematode order Oxyurida is an interesting parasite group for studying the evolution of parasitism as it includes parasites of both invertebrates and vertebrates. In our survey, we found that the smokybrown cockroach Periplaneta fuliginosa was primarily infected with only one nematode species Leidynema appendiculatum. In two cases, L. appendiculatum was isolated from two additional cockroach species Pycnoscelus surinamensis, sold in Japan as a reptile food, and Blatta lateralis, captured in the field and cultured in the laboratory. Inoculation of L. appendiculatum into three additional cockroach species P. japonica, Blattella nipponica, and P. surinamensis also resulted in parasitism. Infection prevalence was high, and timing of postembryonic development from hatched nematode larva to mature adult in these hosts was identical with that in P. fuliginosa. While ecological interactions strongly determine the host range, such broad infectivity is still possible in this parasitic nematode.}, } @article {pmid29721266, year = {2018}, author = {Lajoie, G and Vellend, M}, title = {Characterizing the contribution of plasticity and genetic differentiation to community-level trait responses to environmental change.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3895-3907}, pmid = {29721266}, issn = {2045-7758}, abstract = {The match between functional trait variation in communities and environmental gradients is maintained by three processes: phenotypic plasticity and genetic differentiation (intraspecific processes), and species turnover (interspecific). Recently, evidence has emerged suggesting that intraspecific variation might have a potentially large role in driving functional community composition and response to environmental change. However, empirical evidence quantifying the respective importance of phenotypic plasticity and genetic differentiation relative to species turnover is still lacking. We performed a reciprocal transplant experiment using a common herbaceous plant species (Oxalis montana) among low-, mid-, and high-elevation sites to first quantify the contributions of plasticity and genetic differentiation in driving intraspecific variation in three traits: height, specific leaf area, and leaf area. We next compared the contributions of these intraspecific drivers of community trait-environment matching to that of species turnover, which had been previously assessed along the same elevational gradient. Plasticity was the dominant driver of intraspecific trait variation across elevation in all traits, with only a small contribution of genetic differentiation among populations. Local adaptation was not detected to a major extent along the gradient. Fitness components were greatest in O. montana plants with trait values closest to the local community-weighted means, thus supporting the common assumption that community-weighted mean trait values represent selective optima. Our results suggest that community-level trait responses to ongoing climate change should be mostly mediated by species turnover, even at the small spatial scale of our study, with an especially small contribution of evolutionary adaptation within species.}, } @article {pmid29721265, year = {2018}, author = {Wordley, CFR and Sankaran, M and Mudappa, D and Altringham, JD}, title = {Heard but not seen: Comparing bat assemblages and study methods in a mosaic landscape in the Western Ghats of India.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3883-3894}, pmid = {29721265}, issn = {2045-7758}, abstract = {We used capture (mist-netting) and acoustic methods to compare the species richness, abundance, and composition of a bat assemblage in different habitats in the Western Ghats of India. In the tropics, catching bats has been more commonly used as a survey method than acoustic recordings. In our study, acoustic methods based on recording echolocation calls detected greater bat activity and more species than mist-netting. However, some species were detected more frequently or exclusively by capture. Ideally, the two methods should be used together to compensate for the biases in each. Using combined capture and acoustic data, we found that protected forests, forest fragments, and shade coffee plantations hosted similar and diverse species assemblages, although some species were recorded more frequently in protected forests. Tea plantations contained very few species from the overall bat assemblage. In riparian habitats, a strip of forested habitat on the river bank improved the habitat for bats compared to rivers with tea planted up to each bank. Our results show that shade coffee plantations are better bat habitat than tea plantations in biodiversity hotspots. However, if tea is to be the dominant land use, forest fragments and riparian corridors can improve the landscape considerably for bats. We encourage coffee growers to retain traditional plantations with mature native trees, rather than reverting to sun grown coffee or coffee shaded by a few species of timber trees.}, } @article {pmid29721264, year = {2018}, author = {García-Navas, V and Rodríguez-Rey, M and Marki, PZ and Christidis, L}, title = {Environmental determinism, and not interspecific competition, drives morphological variability in Australasian warblers (Acanthizidae).}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3871-3882}, pmid = {29721264}, issn = {2045-7758}, abstract = {Interspecific competition is thought to play a key role in determining the coexistence of closely related species within adaptive radiations. Competition for ecological resources can lead to different outcomes from character displacement to, ultimately, competitive exclusion. Accordingly, divergent natural selection should disfavor those species that are the most similar to their competitor in resource use, thereby increasing morphological disparity. Here, we examined ecomorphological variability within an Australo-Papuan bird radiation, the Acanthizidae, which include both allopatric and sympatric complexes. In addition, we investigated whether morphological similarities between species are related to environmental factors at fine scale (foraging niche) and/or large scale (climate). Contrary to that predicted by the competition hypothesis, we did not find a significant correlation between the morphological similarities found between species and their degree of range overlap. Comparative modeling based on both a priori and data-driven identification of selective regimes suggested that foraging niche is a poor predictor of morphological variability in acanthizids. By contrast, our results indicate that climatic conditions were an important factor in the formation of morphological variation. We found a significant negative correlation between species scores for PC1 (positively associated to tarsus length and tail length) and both temperature and precipitation, whereas PC2 (positively associated to bill length and wing length) correlated positively with precipitation. In addition, we found that species inhabiting the same region are closer to each other in morphospace than to species outside that region regardless of genus to which they belong or its foraging strategy. Our results indicate that the conservative body form of acanthizids is one that can work under a wide variety of environments (an all-purpose morphology), and the observed interspecific similarity is probably driven by the common response to environment.}, } @article {pmid29721263, year = {2018}, author = {Yang, L and Zhang, C and Chen, M and Li, J and Yang, L and Huo, Z and Ahmad, S and Luan, X}, title = {Long-term ecological data for conservation: Range change in the black-billed capercaillie (Tetrao urogalloides) in northeast China (1970s-2070s).}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3862-3870}, pmid = {29721263}, issn = {2045-7758}, abstract = {Long-term ecological data can be an effective tool to help ecologists integrate future projections with historical contexts and provide unique insights into the long-term dynamics of endangered species. However, hampered by data limitations, including incomplete and spatially biased data, relatively few studies have used multidecadal datasets or have examined changes in biogeography from a historical perspective. The black-billed capercaillie (Tetrao urogalloides) is a large capercaillie (classified as Least Concern [LC] on the IUCN red list) that has undergone a dramatic decline in population during the late 20th century and is considered endangered. Its conservation status is pessimistic, and the species requires immediate protection. Therefore, we supplemented a historical dataset to identify changes in this bird's range and population in northeast China over the long term. The study area spanned Heilongjiang Province, Jilin Province, and the northeast corner of Inner Mongolia in northeast China. We integrated an ecological niche model (BIOMOD2) with long-term ecological data on this species to estimate the magnitude of change in distribution over time. Our results revealed a 35.25% reduction in the current distribution of this species compared to their potential distribution in the 1970s. This decline is expected to continue under climate change. For example, the future range loss was estimated to be 38.79 ± 0.22% (8.64-90.19%), and the actual state could be worse, because the baseline range of the model was greater than the real range in the 2000s, showing a 12.39% overestimation. To overcome this poor outlook, a conservation strategy should be established in sensitive areas, including the southwestern Greater Khingan Mountains and northern Lesser Khingan Mountains. Actions that should be considered include field investigations, establishing a monitor network, designing ecological corridors, and cooperating with local inhabitants, governments, and conservation biologists to improve the conservation of the black-billed capercaillie.}, } @article {pmid29721262, year = {2018}, author = {Yang, B and Pang, X and Bao, W and Zhou, K}, title = {Thinning-induced canopy opening exerted a specific effect on soil nematode community.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3851-3861}, pmid = {29721262}, issn = {2045-7758}, abstract = {Changes in microclimate, soil physicochemical properties, understory vegetation cover, diversity, and composition as well as soil microbial community resulting from silvicultural practices are expected to alter soil food webs. Here, we investigated whether and how contrasting-sized canopy openings affect soil nematode community within a 30 year-aged spruce plantation. The results indicated that the responses of soil nematodes to canopy opening size were dependant on their feeding habit. The abundance of total nematodes and that of free-living nematodes was negatively correlated with soil bulk density, whereas the abundance of omnivore-predators was negatively correlated with soil bulk density and shrubs cover, respectively. The ratio of the sum abundance of predators and omnivores to the plant parasites' abundance, Simpson's dominance index, Pielou's evenness index, and sigma maturity index, maturity index (MI), MI 2-5, basal index, enrichment index, and structure index was sensitive to alteration in canopy opening size. Multivariate analysis indicated that thinning-induced gap size resulted in contrasting nematode assemblages. In conclusion, soil nematodes should be integrated as an indicator to monitor soil multifunctionality change due to thinning.}, } @article {pmid29721261, year = {2018}, author = {Xu, J and Wang, Q and Kong, M}, title = {Livelihood changes matter for the sustainability of ecological restoration: A case analysis of the Grain for Green Program in China's largest Giant Panda Reserve.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3842-3850}, pmid = {29721261}, issn = {2045-7758}, abstract = {Payments for ecosystem services (PES) are expected to promote ecological restoration while simultaneously improving human livelihoods. As an adaptive management tool, PES programs should be dynamic and adjusted according to changing natural and socio-economic contexts. Taking the implementation of China's famous ecological restoration policy known as the Grain for Green Program (GGP) in the Wolong National Nature Reserve as an example, we analyzed changes in the livelihood capitals and strategies of local households that had participated in the GGP over a 10-year period and discussed the implications of these changes for the next stage of the program's implementation. Data were collected from a locally implemented questionnaire in both 2004 and 2015. We found that local livelihood capitals and strategies had experienced dramatic change over the 10-year period. Natural capital decreased and was unequally distributed among local respondents. In terms of financial capital, despite that agricultural and nonagricultural income increased, compensation from the GGP decreased and did not keep pace with increasing cost of cropland, household income and more broadly national economic development and inflation. Regarding human capital, the local labor force is facing huge transformational pressures. In particular, there is a increase in the supply of local labor force aged between 21 and 40 and the implications of this for the future of the GGP should be given more attention. The findings have demonstrated that: Some changes in participants' livelihood were expected by the GGP but were not evenly distributed among the participants; and PES programs are embedded in changing and multi-dimensional socio-economic contexts, and so their design and implementation must be coordinated with other related policies if they are to achieve long-term success.}, } @article {pmid29721260, year = {2018}, author = {Hoefnagel, KN and de Vries, EHJL and Jongejans, E and Verberk, WCEP}, title = {The temperature-size rule in Daphnia magna across different genetic lines and ontogenetic stages: Multiple patterns and mechanisms.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3828-3841}, pmid = {29721260}, issn = {2045-7758}, abstract = {Ectotherms tend to grow faster, but reach a smaller size when reared under warmer conditions. This temperature-size rule (TSR) is a widespread phenomenon. Despite the generality of this pattern, no general explanation has been found. We therefore tested the relative importance of two proposed mechanisms for the TSR: (1) a stronger increase in development rate relative to growth rate at higher temperatures, which would cause a smaller size at maturity, and (2) resource limitation placing stronger constraints on growth in large individuals at higher temperatures, which would cause problems with attaining a large size in warm conditions. We raised Daphnia magna at eight temperatures to assess their size at maturity, asymptotic size, and size of their offspring. We used three clonal lines that differed in asymptotic size and growth rate. A resource allocation model was developed and fitted to our empirical data to explore the effect of both mechanisms for the TSR. The genetic lines of D. magna showed different temperature dependence of growth and development rates resulting in different responses for size at maturity. Also, at warm temperatures, growth was constrained in large, but not in small individuals. The resource allocation model could fit these empirical data well. Based on our empirical results and model explorations, the TSR of D. magna at maturity is best explained by a stronger increase in development rate relative to growth rate at high temperature, and the TSR at asymptotic size is best explained by a size-dependent and temperature-dependent constraint on growth, although resource limitation could also affect size at maturity. In conclusion, the TSR can take different forms for offspring size, size at maturity, and asymptotic size and each form can arise from its own mechanism, which could be an essential step toward finding a solution to this century-old puzzle.}, } @article {pmid29721259, year = {2018}, author = {Nicolaus, M and Edelaar, P}, title = {Comparing the consequences of natural selection, adaptive phenotypic plasticity, and matching habitat choice for phenotype-environment matching, population genetic structure, and reproductive isolation in meta-populations.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3815-3827}, pmid = {29721259}, issn = {2045-7758}, abstract = {Organisms commonly experience significant spatiotemporal variation in their environments. In response to such heterogeneity, different mechanisms may act that enhance ecological performance locally. However, depending on the nature of the mechanism involved, the consequences for populations may differ greatly. Building on a previous model that investigated the conditions under which different adaptive mechanisms (co)evolve, this study compares the ecological and evolutionary population consequences of three very different responses to environmental heterogeneity: matching habitat choice (directed gene flow), adaptive plasticity (associated with random gene flow), and divergent natural selection. Using individual-based simulations, we show that matching habitat choice can have a greater adaptive potential than plasticity or natural selection: it allows for local adaptation while protecting genetic polymorphism despite global mating or strong environmental changes. Our simulations further reveal that increasing environmental fluctuations and unpredictability generally favor the emergence of specialist genotypes but that matching habitat choice is better at preventing local maladaptation by individuals. This confirms that matching habitat choice can speed up the genetic divergence among populations, cause indirect assortative mating via spatial clustering, and hence even facilitate sympatric speciation. This study highlights the potential importance of directed dispersal in local adaptation and speciation, stresses the difficulty of deriving its operation from nonexperimental observational data alone, and helps define a set of ecological conditions which should favor its emergence and subsequent detection in nature.}, } @article {pmid29721258, year = {2018}, author = {Pulgarín-R, PC and Gómez, JP and Robinson, S and Ricklefs, RE and Cadena, CD}, title = {Host species, and not environment, predicts variation in blood parasite prevalence, distribution, and diversity along a humidity gradient in northern South America.}, journal = {Ecology and evolution}, volume = {8}, number = {8}, pages = {3800-3814}, pmid = {29721258}, issn = {2045-7758}, support = {R01 GM117617/GM/NIGMS NIH HHS/United States ; }, abstract = {Environmental factors strongly influence the ecology and evolution of vector-borne infectious diseases. However, our understanding of the influence of climatic variation on host-parasite interactions in tropical systems is rudimentary. We studied five species of birds and their haemosporidian parasites (Plasmodium and Haemoproteus) at 16 sampling sites to understand how environmental heterogeneity influences patterns of parasite prevalence, distribution, and diversity across a marked gradient in water availability in northern South America. We used molecular methods to screen for parasite infections and to identify parasite lineages. To characterize spatial heterogeneity in water availability, we used weather-station and remotely sensed climate data. We estimated parasite prevalence while accounting for spatial autocorrelation, and used a model selection approach to determine the effect of variables related to water availability and host species on prevalence. The prevalence, distribution, and lineage diversity of haemosporidian parasites varied among localities and host species, but we found no support for the hypothesis that the prevalence and diversity of parasites increase with increasing water availability. Host species and host × climate interactions had stronger effects on infection prevalence, and parasite lineages were strongly associated with particular host species. Because climatic variables had little effect on the overall prevalence and lineage diversity of haemosporidian parasites across study sites, our results suggest that independent host-parasite dynamics may influence patterns in parasitism in environmentally heterogeneous landscapes.}, } @article {pmid29721151, year = {2018}, author = {Kumar, R and Acharya, V and Singh, D and Kumar, S}, title = {Strategies for high-altitude adaptation revealed from high-quality draft genome of non-violacein producing Janthinobacterium lividum ERGS5:01.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {11}, pmid = {29721151}, issn = {1944-3277}, abstract = {A light pink coloured bacterial strain ERGS5:01 isolated from glacial stream water of Sikkim Himalaya was affiliated to Janthinobacterium lividum based on 16S rRNA gene sequence identity and phylogenetic clustering. Whole genome sequencing was performed for the strain to confirm its taxonomy as it lacked the typical violet pigmentation of the genus and also to decipher its survival strategy at the aquatic ecosystem of high elevation. The PacBio RSII sequencing generated genome of 5,168,928 bp with 4575 protein-coding genes and 118 RNA genes. Whole genome-based multilocus sequence analysis clustering, in silico DDH similarity value of 95.1% and, the ANI value of 99.25% established the identity of the strain ERGS5:01 (MCC 2953) as a non-violacein producing J. lividum. The genome comparisons across genus Janthinobacterium revealed an open pan-genome with the scope of the addition of new orthologous cluster to complete the genomic inventory. The genomic insight provided the genetic basis of freezing and frequent freeze-thaw cycle tolerance and, for industrially important enzymes. Extended insight into the genome provided clues of crucial genes associated with adaptation in the harsh aquatic ecosystem of high altitude.}, } @article {pmid29720870, year = {2018}, author = {Antonets, KS and Kliver, SF and Nizhnikov, AA}, title = {Exploring Proteins Containing Amyloidogenic Regions in the Proteomes of Bacteria of the Order Rhizobiales.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318768781}, pmid = {29720870}, issn = {1176-9343}, abstract = {Amyloids are protein fibrils with a highly ordered spatial structure called cross-β. To date, amyloids were shown to be implicated in a wide range of biological processes, both pathogenic and functional. In bacteria, functional amyloids are involved in forming biofilms, storing toxins, overcoming the surface tension, and other functions. Rhizobiales represent an economically important group of Alphaproteobacteria, various species of which are not only capable of fixing nitrogen in the symbiosis with leguminous plants but also act as the causative agents of infectious diseases in animals and plants. Here, we implemented bioinformatic screening for potentially amyloidogenic proteins in the proteomes of more than 80 species belonging to the order Rhizobiales. Using SARP (Sequence Analysis based on the Ranking of Probabilities) and Waltz bioinformatic algorithms, we identified the biological processes, where potentially amyloidogenic proteins are overrepresented. We detected protein domains and regions associated with amyloidogenic sequences in the proteomes of various Rhizobiales species. We demonstrated that amyloidogenic regions tend to occur in the membrane or extracellular proteins, many of which are involved in pathogenesis-related processes, including adhesion, assembly of flagellum, and transport of siderophores and lipopolysaccharides, and contain domains typical of the virulence factors (hemolysin, RTX, YadA, LptD); some of them (rhizobiocins, LptD) are also related to symbiosis.}, } @article {pmid29720707, year = {2018}, author = {Arciola, CR and Campoccia, D and Montanaro, L}, title = {Implant infections: adhesion, biofilm formation and immune evasion.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {397-409}, doi = {10.1038/s41579-018-0019-y}, pmid = {29720707}, issn = {1740-1534}, abstract = {Medical device-associated infections account for a large proportion of hospital-acquired infections. A variety of opportunistic pathogens can cause implant infections, depending on the type of the implant and on the anatomical site of implantation. The success of these versatile pathogens depends on rapid adhesion to virtually all biomaterial surfaces and survival in the hostile host environment. Biofilm formation on implant surfaces shelters the bacteria and encourages persistence of infection. Furthermore, implant-infecting bacteria can elude innate and adaptive host defences as well as biocides and antibiotic chemotherapies. In this Review, we explore the fundamental pathogenic mechanisms underlying implant infections, highlighting orthopaedic implants and Staphylococcus aureus as a prime example, and discuss innovative targets for preventive and therapeutic strategies.}, } @article {pmid29720706, year = {2018}, author = {Pance, A}, title = {Can Wolbachia save the day?.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {396}, doi = {10.1038/s41579-018-0021-4}, pmid = {29720706}, issn = {1740-1534}, } @article {pmid29720662, year = {2018}, author = {Schaub, JR and Huppert, KA and Kurial, SNT and Hsu, BY and Cast, AE and Donnelly, B and Karns, RA and Chen, F and Rezvani, M and Luu, HY and Mattis, AN and Rougemont, AL and Rosenthal, P and Huppert, SS and Willenbring, H}, title = {De novo formation of the biliary system by TGFβ-mediated hepatocyte transdifferentiation.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {247-251}, doi = {10.1038/s41586-018-0075-5}, pmid = {29720662}, issn = {1476-4687}, support = {P30 DK078392/DK/NIDDK NIH HHS/United States ; R01 DK078640/DK/NIDDK NIH HHS/United States ; R01 DK107553/DK/NIDDK NIH HHS/United States ; P30 DK026743/DK/NIDDK NIH HHS/United States ; }, mesh = {Alagille Syndrome/pathology ; Animals ; Bile Ducts/cytology/metabolism ; Biliary Tract/*cytology/*metabolism ; Cell Proliferation ; *Cell Transdifferentiation ; Epithelial Cells/cytology ; Female ; Hepatocytes/*cytology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Notch/metabolism ; Signal Transduction ; Transforming Growth Factor beta/*metabolism ; }, abstract = {Transdifferentiation is a complete and stable change in cell identity that serves as an alternative to stem-cell-mediated organ regeneration. In adult mammals, findings of transdifferentiation have been limited to the replenishment of cells lost from preexisting structures, in the presence of a fully developed scaffold and niche1. Here we show that transdifferentiation of hepatocytes in the mouse liver can build a structure that failed to form in development-the biliary system in a mouse model that mimics the hepatic phenotype of human Alagille syndrome (ALGS)2. In these mice, hepatocytes convert into mature cholangiocytes and form bile ducts that are effective in draining bile and persist after the cholestatic liver injury is reversed, consistent with transdifferentiation. These findings redefine hepatocyte plasticity, which appeared to be limited to metaplasia, that is, incomplete and transient biliary differentiation as an adaptation to cell injury, based on previous studies in mice with a fully developed biliary system3-6. In contrast to bile duct development7-9, we show that de novo bile duct formation by hepatocyte transdifferentiation is independent of NOTCH signalling. We identify TGFβ signalling as the driver of this compensatory mechanism and show that it is active in some patients with ALGS. Furthermore, we show that TGFβ signalling can be targeted to enhance the formation of the biliary system from hepatocytes, and that the transdifferentiation-inducing signals and remodelling capacity of the bile-duct-deficient liver can be harnessed with transplanted hepatocytes. Our results define the regenerative potential of mammalian transdifferentiation and reveal opportunities for the treatment of ALGS and other cholestatic liver diseases.}, } @article {pmid29720661, year = {2018}, author = {Ingicco, T and van den Bergh, GD and Jago-On, C and Bahain, JJ and Chacón, MG and Amano, N and Forestier, H and King, C and Manalo, K and Nomade, S and Pereira, A and Reyes, MC and Sémah, AM and Shao, Q and Voinchet, P and Falguères, C and Albers, PCH and Lising, M and Lyras, G and Yurnaldi, D and Rochette, P and Bautista, A and de Vos, J}, title = {Earliest known hominin activity in the Philippines by 709 thousand years ago.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {233-237}, doi = {10.1038/s41586-018-0072-8}, pmid = {29720661}, issn = {1476-4687}, mesh = {Aluminum Silicates ; Animal Migration ; Animals ; Clay ; Electron Spin Resonance Spectroscopy ; *Fossils ; Geologic Sediments ; History, Ancient ; *Hominidae ; Philippines ; Radiometric Dating ; *Tool Use Behavior ; }, abstract = {Over 60 years ago, stone tools and remains of megafauna were discovered on the Southeast Asian islands of Flores, Sulawesi and Luzon, and a Middle Pleistocene colonization by Homo erectus was initially proposed to have occurred on these islands1-4. However, until the discovery of Homo floresiensis in 2003, claims of the presence of archaic hominins on Wallacean islands were hypothetical owing to the absence of in situ fossils and/or stone artefacts that were excavated from well-documented stratigraphic contexts, or because secure numerical dating methods of these sites were lacking. As a consequence, these claims were generally treated with scepticism 5 . Here we describe the results of recent excavations at Kalinga in the Cagayan Valley of northern Luzon in the Philippines that have yielded 57 stone tools associated with an almost-complete disarticulated skeleton of Rhinoceros philippinensis, which shows clear signs of butchery, together with other fossil fauna remains attributed to stegodon, Philippine brown deer, freshwater turtle and monitor lizard. All finds originate from a clay-rich bone bed that was dated to between 777 and 631 thousand years ago using electron-spin resonance methods that were applied to tooth enamel and fluvial quartz. This evidence pushes back the proven period of colonization 6 of the Philippines by hundreds of thousands of years, and furthermore suggests that early overseas dispersal in Island South East Asia by premodern hominins took place several times during the Early and Middle Pleistocene stages1-4. The Philippines therefore may have had a central role in southward movements into Wallacea, not only of Pleistocene megafauna 7 , but also of archaic hominins.}, } @article {pmid29720660, year = {2018}, author = {Eichel, K and Jullié, D and Barsi-Rhyne, B and Latorraca, NR and Masureel, M and Sibarita, JB and Dror, RO and von Zastrow, M}, title = {Catalytic activation of β-arrestin by GPCRs.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {381-386}, pmid = {29720660}, issn = {1476-4687}, support = {P01 DA010154/DA/NIDA NIH HHS/United States ; T32 GM007810/GM/NIGMS NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; R01 GM127359/GM/NIGMS NIH HHS/United States ; R01 DA012864/DA/NIDA NIH HHS/United States ; U01 NS103522/NS/NINDS NIH HHS/United States ; R01 DA010711/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Biocatalysis ; COS Cells ; Cell Membrane/metabolism ; Cercopithecus aethiops ; HEK293 Cells ; Humans ; Phosphatidylinositols/metabolism ; Protein Transport ; Receptors, G-Protein-Coupled/chemistry/*metabolism ; beta-Arrestins/chemistry/*metabolism ; }, abstract = {β-arrestins are critical regulator and transducer proteins for G-protein-coupled receptors (GPCRs). β-arrestin is widely believed to be activated by forming a stable and stoichiometric GPCR-β-arrestin scaffold complex, which requires and is driven by the phosphorylated tail of the GPCR. Here we demonstrate a distinct and additional mechanism of β-arrestin activation that does not require stable GPCR-β-arrestin scaffolding or the GPCR tail. Instead, it occurs through transient engagement of the GPCR core, which destabilizes a conserved inter-domain charge network in β-arrestin. This promotes capture of β-arrestin at the plasma membrane and its accumulation in clathrin-coated endocytic structures (CCSs) after dissociation from the GPCR, requiring a series of interactions with membrane phosphoinositides and CCS-lattice proteins. β-arrestin clustering in CCSs in the absence of the upstream activating GPCR is associated with a β-arrestin-dependent component of the cellular ERK (extracellular signal-regulated kinase) response. These results delineate a discrete mechanism of cellular β-arrestin function that is activated catalytically by GPCRs.}, } @article {pmid29720659, year = {2018}, author = {Wu, J and Xu, J and Liu, B and Yao, G and Wang, P and Lin, Z and Huang, B and Wang, X and Li, T and Shi, S and Zhang, N and Duan, F and Ming, J and Zhang, X and Niu, W and Song, W and Jin, H and Guo, Y and Dai, S and Hu, L and Fang, L and Wang, Q and Li, Y and Li, W and Na, J and Xie, W and Sun, Y}, title = {Chromatin analysis in human early development reveals epigenetic transition during ZGA.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {256-260}, doi = {10.1038/s41586-018-0080-8}, pmid = {29720659}, issn = {1476-4687}, mesh = {Animals ; Binding Sites ; Chromatin/*genetics/*metabolism ; CpG Islands/genetics ; DNA Methylation ; Embryo, Mammalian/cytology/embryology/*metabolism ; Embryonic Development/*genetics ; Embryonic Stem Cells/cytology ; *Epigenesis, Genetic ; Female ; Gene Silencing ; Genome/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Mice ; Oocytes/cytology/metabolism ; Pluripotent Stem Cells/cytology ; Promoter Regions, Genetic/genetics ; Transcription Factors/metabolism ; Transposases/metabolism ; Zygote/*metabolism ; }, abstract = {Upon fertilization, drastic chromatin reorganization occurs during preimplantation development 1 . However, the global chromatin landscape and its molecular dynamics in this period remain largely unexplored in humans. Here we investigate chromatin states in human preimplantation development using an improved assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) 2 . We find widespread accessible chromatin regions in early human embryos that overlap extensively with putative cis-regulatory sequences and transposable elements. Integrative analyses show both conservation and divergence in regulatory circuitry between human and mouse early development, and between human pluripotency in vivo and human embryonic stem cells. In addition, we find widespread open chromatin regions before zygotic genome activation (ZGA). The accessible chromatin loci are readily found at CpG-rich promoters. Unexpectedly, many others reside in distal regions that overlap with DNA hypomethylated domains in human oocytes and are enriched for transcription factor-binding sites. A large portion of these regions then become inaccessible after ZGA in a transcription-dependent manner. Notably, such extensive chromatin reorganization during ZGA is conserved in mice and correlates with the reprogramming of the non-canonical histone mark H3K4me3, which is uniquely linked to genome silencing3-5. Taken together, these data not only reveal a conserved principle that underlies the chromatin transition during mammalian ZGA, but also help to advance our understanding of epigenetic reprogramming during human early development and in vitro fertilization.}, } @article {pmid29720658, year = {2018}, author = {Parker, JG and Marshall, JD and Ahanonu, B and Wu, YW and Kim, TH and Grewe, BF and Zhang, Y and Li, JZ and Ding, JB and Ehlers, MD and Schnitzer, MJ}, title = {Diametric neural ensemble dynamics in parkinsonian and dyskinetic states.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {177-182}, doi = {10.1038/s41586-018-0090-6}, pmid = {29720658}, issn = {1476-4687}, support = {R01 NS091144/NS/NINDS NIH HHS/United States ; R01 NS103037/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Calcium Signaling ; Dopamine/deficiency/*metabolism ; Dyskinesias/etiology/metabolism/*pathology/*physiopathology ; Female ; Levodopa/metabolism/pharmacology ; Male ; Mice ; Models, Biological ; Movement/drug effects ; Neostriatum/metabolism/pathology/physiopathology ; Neurons/*metabolism ; Parkinsonian Disorders/metabolism/*pathology/*physiopathology ; Receptors, Dopamine D1/agonists/metabolism ; Receptors, Dopamine D2/agonists/metabolism ; }, abstract = {Loss of dopamine in Parkinson's disease is hypothesized to impede movement by inducing hypo- and hyperactivity in striatal spiny projection neurons (SPNs) of the direct (dSPNs) and indirect (iSPNs) pathways in the basal ganglia, respectively. The opposite imbalance might underlie hyperkinetic abnormalities, such as dyskinesia caused by treatment of Parkinson's disease with the dopamine precursor L-DOPA. Here we monitored thousands of SPNs in behaving mice, before and after dopamine depletion and during L-DOPA-induced dyskinesia. Normally, intermingled clusters of dSPNs and iSPNs coactivated before movement. Dopamine depletion unbalanced SPN activity rates and disrupted the movement-encoding iSPN clusters. Matching their clinical efficacy, L-DOPA or agonism of the D2 dopamine receptor reversed these abnormalities more effectively than agonism of the D1 dopamine receptor. The opposite pathophysiology arose in L-DOPA-induced dyskinesia, during which iSPNs showed hypoactivity and dSPNs showed unclustered hyperactivity. Therefore, both the spatiotemporal profiles and rates of SPN activity appear crucial to striatal function, and next-generation treatments for basal ganglia disorders should target both facets of striatal activity.}, } @article {pmid29720657, year = {2018}, author = {Walsh, RM and Roh, SH and Gharpure, A and Morales-Perez, CL and Teng, J and Hibbs, RE}, title = {Structural principles of distinct assemblies of the human α4β2 nicotinic receptor.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {261-265}, pmid = {29720657}, issn = {1476-4687}, support = {U24 GM116787/GM/NIGMS NIH HHS/United States ; P41 GM103832/GM/NIGMS NIH HHS/United States ; R01 DA042072/DA/NIDA NIH HHS/United States ; R01 NS095899/NS/NINDS NIH HHS/United States ; R21 DA037492/DA/NIDA NIH HHS/United States ; R01 GM079429/GM/NIGMS NIH HHS/United States ; R33 DA037492/DA/NIDA NIH HHS/United States ; T32 GM008203/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; *Cryoelectron Microscopy ; Electric Conductivity ; Female ; Humans ; Immunoglobulin Fab Fragments/immunology/pharmacology ; Ion Channel Gating ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Nicotine/chemistry/metabolism/pharmacology ; Protein Isoforms/chemistry/immunology/metabolism/ultrastructure ; Protein Structure, Quaternary/drug effects ; Protein Subunits/agonists/*chemistry/immunology/*metabolism ; Receptors, Nicotinic/chemistry/immunology/*metabolism/*ultrastructure ; }, abstract = {Fast chemical communication in the nervous system is mediated by neurotransmitter-gated ion channels. The prototypical member of this class of cell surface receptors is the cation-selective nicotinic acetylcholine receptor. As with most ligand-gated ion channels, nicotinic receptors assemble as oligomers of subunits, usually as hetero-oligomers and often with variable stoichiometries 1 . This intrinsic heterogeneity in protein composition provides fine tunability in channel properties, which is essential to brain function, but frustrates structural and biophysical characterization. The α4β2 subtype of the nicotinic acetylcholine receptor is the most abundant isoform in the human brain and is the principal target in nicotine addiction. This pentameric ligand-gated ion channel assembles in two stoichiometries of α- and β-subunits (2α:3β and 3α:2β). Both assemblies are functional and have distinct biophysical properties, and an imbalance in the ratio of assemblies is linked to both nicotine addiction2,3 and congenital epilepsy4,5. Here we leverage cryo-electron microscopy to obtain structures of both receptor assemblies from a single sample. Antibody fragments specific to β2 were used to 'break' symmetry during particle alignment and to obtain high-resolution reconstructions of receptors of both stoichiometries in complex with nicotine. The results reveal principles of subunit assembly and the structural basis of the distinctive biophysical and pharmacological properties of the two different stoichiometries of this receptor.}, } @article {pmid29720656, year = {2018}, author = {Lucamarini, M and Yuan, ZL and Dynes, JF and Shields, AJ}, title = {Overcoming the rate-distance limit of quantum key distribution without quantum repeaters.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {400-403}, doi = {10.1038/s41586-018-0066-6}, pmid = {29720656}, issn = {1476-4687}, abstract = {Quantum key distribution (QKD)1,2 allows two distant parties to share encryption keys with security based on physical laws. Experimentally, QKD has been implemented via optical means, achieving key rates of 1.26 megabits per second over 50 kilometres of standard optical fibre 3 and of 1.16 bits per hour over 404 kilometres of ultralow-loss fibre in a measurement-device-independent configuration 4 . Increasing the bit rate and range of QKD is a formidable, but important, challenge. A related target, which is currently considered to be unfeasible without quantum repeaters5-7, is overcoming the fundamental rate-distance limit of QKD 8 . This limit defines the maximum possible secret key rate that two parties can distil at a given distance using QKD and is quantified by the secret-key capacity of the quantum channel 9 that connects the parties. Here we introduce an alternative scheme for QKD whereby pairs of phase-randomized optical fields are first generated at two distant locations and then combined at a central measuring station. Fields imparted with the same random phase are 'twins' and can be used to distil a quantum key. The key rate of this twin-field QKD exhibits the same dependence on distance as does a quantum repeater, scaling with the square-root of the channel transmittance, irrespective of who (malicious or otherwise) is in control of the measuring station. However, unlike schemes that involve quantum repeaters, ours is feasible with current technology and presents manageable levels of noise even on 550 kilometres of standard optical fibre. This scheme is a promising step towards overcoming the rate-distance limit of QKD and greatly extending the range of secure quantum communications.}, } @article {pmid29720655, year = {2018}, author = {Latorraca, NR and Wang, JK and Bauer, B and Townshend, RJL and Hollingsworth, SA and Olivieri, JE and Xu, HE and Sommer, ME and Dror, RO}, title = {Molecular mechanism of GPCR-mediated arrestin activation.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {452-456}, pmid = {29720655}, issn = {1476-4687}, support = {T15-LM007033-33/NH/NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; R01 GM127359/GM/NIGMS NIH HHS/United States ; T15 LM007033/LM/NLM NIH HHS/United States ; R01 GM116961/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Arrestins/chemistry/*metabolism ; Cattle ; Ligands ; Receptors, G-Protein-Coupled/chemistry/*metabolism ; Signal Transduction ; Spectrometry, Fluorescence ; }, abstract = {Despite intense interest in discovering drugs that cause G-protein-coupled receptors (GPCRs) to selectively stimulate or block arrestin signalling, the structural mechanism of receptor-mediated arrestin activation remains unclear1,2. Here we reveal this mechanism through extensive atomic-level simulations of arrestin. We find that the receptor's transmembrane core and cytoplasmic tail-which bind distinct surfaces on arrestin-can each independently stimulate arrestin activation. We confirm this unanticipated role of the receptor core, and the allosteric coupling between these distant surfaces of arrestin, using site-directed fluorescence spectroscopy. The effect of the receptor core on arrestin conformation is mediated primarily by interactions of the intracellular loops of the receptor with the arrestin body, rather than the marked finger-loop rearrangement that is observed upon receptor binding. In the absence of a receptor, arrestin frequently adopts active conformations when its own C-terminal tail is disengaged, which may explain why certain arrestins remain active long after receptor dissociation. Our results, which suggest that diverse receptor binding modes can activate arrestin, provide a structural foundation for the design of functionally selective ('biased') GPCR-targeted ligands with desired effects on arrestin signalling.}, } @article {pmid29720654, year = {2018}, author = {Harumoto, T and Lemaitre, B}, title = {Male-killing toxin in a bacterial symbiont of Drosophila.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {252-255}, pmid = {29720654}, issn = {1476-4687}, mesh = {Animals ; Bacterial Proteins/*metabolism ; Bacterial Toxins/*metabolism ; Dosage Compensation, Genetic/genetics ; Drosophila melanogaster/embryology/genetics/*microbiology ; Female ; Male ; *Sex Characteristics ; *Sex Ratio ; Spiroplasma/*pathogenicity/*physiology ; *Symbiosis ; X Chromosome/genetics ; }, abstract = {Several lineages of symbiotic bacteria in insects selfishly manipulate host reproduction to spread in a population 1 , often by distorting host sex ratios. Spiroplasma poulsonii2,3 is a helical and motile, Gram-positive symbiotic bacterium that resides in a wide range of Drosophila species 4 . A notable feature of S. poulsonii is male killing, whereby the sons of infected female hosts are selectively killed during development1,2. Although male killing caused by S. poulsonii has been studied since the 1950s, its underlying mechanism is unknown. Here we identify an S. poulsonii protein, designated Spaid, whose expression induces male killing. Overexpression of Spaid in D. melanogaster kills males but not females, and induces massive apoptosis and neural defects, recapitulating the pathology observed in S. poulsonii-infected male embryos5-11. Our data suggest that Spaid targets the dosage compensation machinery on the male X chromosome to mediate its effects. Spaid contains ankyrin repeats and a deubiquitinase domain, which are required for its subcellular localization and activity. Moreover, we found a laboratory mutant strain of S. poulsonii with reduced male-killing ability and a large deletion in the spaid locus. Our study has uncovered a bacterial protein that affects host cellular machinery in a sex-specific way, which is likely to be the long-searched-for factor responsible for S. poulsonii-induced male killing.}, } @article {pmid29720653, year = {2018}, author = {Vandewauw, I and De Clercq, K and Mulier, M and Held, K and Pinto, S and Van Ranst, N and Segal, A and Voet, T and Vennekens, R and Zimmermann, K and Vriens, J and Voets, T}, title = {Publisher Correction: A TRP channel trio mediates acute noxious heat sensing.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {E7}, doi = {10.1038/s41586-018-0100-8}, pmid = {29720653}, issn = {1476-4687}, abstract = {In this Letter, the trace is missing in Fig. 1e. This error has been corrected online.}, } @article {pmid29720652, year = {2018}, author = {Turner, BL and Brenes-Arguedas, T and Condit, R}, title = {Publisher Correction: Pervasive phosphorus limitation of tree species but not communities in tropical forests.}, journal = {Nature}, volume = {559}, number = {7713}, pages = {E4}, doi = {10.1038/s41586-018-0099-x}, pmid = {29720652}, issn = {1476-4687}, abstract = {In this Letter, the y axis of the right-hand panel of Fig. 2a was mislabelled 'Phosphomonoesterase' instead of 'Phosphodiesterase'. This error has been corrected online.}, } @article {pmid29720651, year = {2018}, author = {Patton, GC and Olsson, CA and Skirbekk, V and Saffery, R and Wlodek, ME and Azzopardi, PS and Stonawski, M and Rasmussen, B and Spry, E and Francis, K and Bhutta, ZA and Kassebaum, NJ and Mokdad, AH and Murray, CJL and Prentice, AM and Reavley, N and Sheehan, P and Sweeny, K and Viner, RM and Sawyer, SM}, title = {Publisher Correction: Adolescence and the next generation.}, journal = {Nature}, volume = {559}, number = {7712}, pages = {E1}, doi = {10.1038/s41586-018-0069-3}, pmid = {29720651}, issn = {1476-4687}, abstract = {In Fig. 4a of this Analysis, owing to an error during the production process, the year in the header of the right column was '2016' rather than '2010'. In addition, in the HTML version of the Analysis, Table 1 was formatted incorrectly. These errors have been corrected online.}, } @article {pmid29720650, year = {2018}, author = {Gaudelli, NM and Komor, AC and Rees, HA and Packer, MS and Badran, AH and Bryson, DI and Liu, DR}, title = {Publisher Correction: Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage.}, journal = {Nature}, volume = {559}, number = {7714}, pages = {E8}, doi = {10.1038/s41586-018-0070-x}, pmid = {29720650}, issn = {1476-4687}, abstract = {In this Article, owing to an error during the production process, in Fig. 1a, the dark blue and light blue wedges were incorrectly labelled as 'G•C → T•A' and 'G•C → A•T', instead of 'C•G → T•A' and 'C•G → A•T', respectively. Fig. 1 has been corrected online.}, } @article {pmid29720649, year = {2018}, author = {Shoshkes-Carmel, M and Wang, YJ and Wangensteen, KJ and Tóth, B and Kondo, A and Massasa, EE and Itzkovitz, S and Kaestner, KH}, title = {Subepithelial telocytes are an important source of Wnts that supports intestinal crypts.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {242-246}, pmid = {29720649}, issn = {1476-4687}, support = {P30 DK019525/DK/NIDDK NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; R37 DK053839/DK/NIDDK NIH HHS/United States ; }, mesh = {Acyltransferases/deficiency/genetics/metabolism ; Animals ; Cell Proliferation ; *Cell Self Renewal ; Forkhead Transcription Factors/metabolism ; Intestinal Mucosa/*cytology ; Ligands ; Male ; Membrane Proteins/deficiency/genetics/metabolism ; Mice ; Mice, Inbred C57BL ; RNA, Messenger/genetics/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/metabolism ; Telocytes/*metabolism ; Wnt Proteins/*metabolism ; *Wnt Signaling Pathway ; }, abstract = {Tissues that undergo rapid cellular turnover, such as the mammalian haematopoietic system or the intestinal epithelium, are dependent on stem and progenitor cells that proliferate to provide differentiated cells to maintain organismal health. Stem and progenitor cells, in turn, are thought to rely on signals and growth factors provided by local niche cells to support their function and self-renewal. Several cell types have been hypothesized to provide the signals required for the proliferation and differentiation of the intestinal stem cells in intestinal crypts1-6. Here we identify subepithelial telocytes as an important source of Wnt proteins, without which intestinal stem cells cannot proliferate and support epithelial renewal. Telocytes are large but rare mesenchymal cells that are marked by expression of FOXL1 and form a subepithelial plexus that extends from the stomach to the colon. While supporting the entire epithelium, FOXL1+ telocytes compartmentalize the production of Wnt ligands and inhibitors to enable localized pathway activation. Conditional genetic ablation of porcupine (Porcn), which is required for functional maturation of all Wnt proteins, in mouse FOXL1+ telocytes causes rapid cessation of Wnt signalling to intestinal crypts, followed by loss of proliferation of stem and transit amplifying cells and impaired epithelial renewal. Thus, FOXL1+ telocytes are an important source of niche signals to intestinal stem cells.}, } @article {pmid29720648, year = {2018}, author = {Ho, H and Miu, A and Alexander, MK and Garcia, NK and Oh, A and Zilberleyb, I and Reichelt, M and Austin, CD and Tam, C and Shriver, S and Hu, H and Labadie, SS and Liang, J and Wang, L and Wang, J and Lu, Y and Purkey, HE and Quinn, J and Franke, Y and Clark, K and Beresini, MH and Tan, MW and Sellers, BD and Maurer, T and Koehler, MFT and Wecksler, AT and Kiefer, JR and Verma, V and Xu, Y and Nishiyama, M and Payandeh, J and Koth, CM}, title = {Structural basis for dual-mode inhibition of the ABC transporter MsbA.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {196-201}, doi = {10.1038/s41586-018-0083-5}, pmid = {29720648}, issn = {1476-4687}, mesh = {ATP-Binding Cassette Transporters/*antagonists & inhibitors/*chemistry/metabolism ; Allosteric Regulation/drug effects ; Anti-Bacterial Agents/*chemistry/*pharmacology ; Bacterial Proteins/*antagonists & inhibitors/*chemistry/metabolism ; Binding Sites/drug effects ; Crystallography, X-Ray ; Dose-Response Relationship, Drug ; Escherichia coli/chemistry ; Hydrocarbons/chemistry/metabolism ; Lipopolysaccharides/chemistry/metabolism/pharmacology ; Models, Molecular ; Protein Domains/drug effects ; Quinolines/*chemistry/*pharmacology ; }, abstract = {The movement of core-lipopolysaccharide across the inner membrane of Gram-negative bacteria is catalysed by an essential ATP-binding cassette transporter, MsbA. Recent structures of MsbA and related transporters have provided insights into the molecular basis of active lipid transport; however, structural information about their pharmacological modulation remains limited. Here we report the 2.9 Å resolution structure of MsbA in complex with G907, a selective small-molecule antagonist with bactericidal activity, revealing an unprecedented mechanism of ABC transporter inhibition. G907 traps MsbA in an inward-facing, lipopolysaccharide-bound conformation by wedging into an architecturally conserved transmembrane pocket. A second allosteric mechanism of antagonism occurs through structural and functional uncoupling of the nucleotide-binding domains. This study establishes a framework for the selective modulation of ABC transporters and provides rational avenues for the design of new antibiotics and other therapeutics targeting this protein family.}, } @article {pmid29720647, year = {2018}, author = {Salay, LD and Ishiko, N and Huberman, AD}, title = {A midline thalamic circuit determines reactions to visual threat.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {183-189}, doi = {10.1038/s41586-018-0078-2}, pmid = {29720647}, issn = {1476-4687}, support = {R01 EY022157/EY/NEI NIH HHS/United States ; U01 NS090562/NS/NINDS NIH HHS/United States ; }, mesh = {Adaptation, Biological ; Animals ; Arousal/*physiology ; Decision Making ; Fear/*physiology/*psychology ; Female ; Male ; Mice ; Midline Thalamic Nuclei/cytology/physiology ; *Neural Pathways ; Photic Stimulation ; Prefrontal Cortex/cytology/physiology ; Thalamus/*cytology/*physiology ; }, abstract = {How our internal state is merged with our visual perception of an impending threat to drive an adaptive behavioural response is not known. Mice respond to visual threats by either freezing or seeking shelter. Here we show that nuclei of the ventral midline thalamus (vMT), the xiphoid nucleus (Xi) and nucleus reuniens (Re), represent crucial hubs in the network controlling behavioural responses to visual threats. The Xi projects to the basolateral amygdala to promote saliency-reducing responses to threats, such as freezing, whereas the Re projects to the medial prefrontal cortex (Re→mPFC) to promote saliency-enhancing, even confrontational responses to threats, such as tail rattling. Activation of the Re→mPFC pathway also increases autonomic arousal in a manner that is rewarding. The vMT is therefore important for biasing how internal states are translated into opposing categories of behavioural responses to perceived threats. These findings may have implications for understanding disorders of arousal and adaptive decision-making, such as phobias, post-traumatic stress and addictions.}, } @article {pmid29720643, year = {2018}, author = {}, title = {North Korea's nuclear site, Mars rocks and CRISPR arguments.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {10-11}, doi = {10.1038/d41586-018-04995-4}, pmid = {29720643}, issn = {1476-4687}, } @article {pmid29720642, year = {2018}, author = {Reardon, S}, title = {After the violence.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {19-24}, doi = {10.1038/d41586-018-04976-7}, pmid = {29720642}, issn = {1476-4687}, mesh = {Adolescent ; Anxiety ; Attitude ; Child ; Cognition ; Colombia ; Empathy ; Female ; Humans ; Male ; Mental Health ; Military Personnel/*psychology ; Politics ; Psychology, Military/*trends ; Psychotherapy ; Stress Disorders, Post-Traumatic/psychology/therapy ; Veterans/*psychology ; Violence/*psychology ; War Crimes/psychology ; *Warfare ; }, } @article {pmid29720640, year = {2018}, author = {}, title = {Nature journals formalize ethical standards for human embryo and stem-cell research.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {6}, doi = {10.1038/d41586-018-05030-2}, pmid = {29720640}, issn = {1476-4687}, mesh = {*Editorial Policies ; Embryo Research/*ethics ; Guidelines as Topic ; Human Embryonic Stem Cells ; Humans ; Periodicals as Topic/*ethics/standards ; Pluripotent Stem Cells ; Stem Cell Research/*ethics ; }, } @article {pmid29720637, year = {2018}, author = {Ma, Y and Zhao, Y and Gong, X and Sun, L and Zheng, Y}, title = {Close the gender gap in Chinese science.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {25-27}, doi = {10.1038/d41586-018-04996-3}, pmid = {29720637}, issn = {1476-4687}, mesh = {Adult ; Age Factors ; Asian Continental Ancestry Group ; China ; Female ; Financing, Organized/organization & administration/statistics & numerical data ; Humans ; Male ; Middle Aged ; Research Personnel/*supply & distribution ; *Science ; Sex Distribution ; Sex Factors ; Sexism/*prevention & control/*statistics & numerical data ; Work-Life Balance ; Workforce ; }, } @article {pmid29720636, year = {2018}, author = {Field, DJ and Hanson, M and Burnham, D and Wilson, LE and Super, K and Ehret, D and Ebersole, JA and Bhullar, BS}, title = {Complete Ichthyornis skull illuminates mosaic assembly of the avian head.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {96-100}, doi = {10.1038/s41586-018-0053-y}, pmid = {29720636}, issn = {1476-4687}, mesh = {Animals ; Beak/anatomy & histology ; Birds/*anatomy & histology/classification ; Dinosaurs/*anatomy & histology ; *Fossils ; Head/anatomy & histology ; Jaw/anatomy & histology ; *Phylogeny ; Skull/*anatomy & histology ; }, abstract = {The skull of living birds is greatly modified from the condition found in their dinosaurian antecedents. Bird skulls have an enlarged, toothless premaxillary beak and an intricate kinetic system that includes a mobile palate and jaw suspensorium. The expanded avian neurocranium protects an enlarged brain and is flanked by reduced jaw adductor muscles. However, the order of appearance of these features and the nature of their earliest manifestations remain unknown. The Late Cretaceous toothed bird Ichthyornis dispar sits in a pivotal phylogenetic position outside living groups: it is close to the extant avian radiation but retains numerous ancestral characters1-3. Although its evolutionary importance continues to be affirmed3-8, no substantial new cranial material of I. dispar has been described beyond incomplete remains recovered in the 1870s. Jurassic and Cretaceous Lagerstätten have yielded important avialan fossils, but their skulls are typically crushed and distorted 9 . Here we report four three-dimensionally preserved specimens of I. dispar-including an unusually complete skull-as well as two previously overlooked elements from the Yale Peabody Museum holotype, YPM 1450. We used these specimens to generate a nearly complete three-dimensional reconstruction of the I. dispar skull using high-resolution computed tomography. Our study reveals that I. dispar had a transitional beak-small, lacking a palatal shelf and restricted to the tips of the jaws-coupled with a kinetic system similar to that of living birds. The feeding apparatus of extant birds therefore evolved earlier than previously thought and its components were functionally and developmentally coordinated. The brain was relatively modern, but the temporal region was unexpectedly dinosaurian: it retained a large adductor chamber bounded dorsally by substantial bony remnants of the ancestral reptilian upper temporal fenestra. This combination of features documents that important attributes of the avian brain and palate evolved before the reduction of jaw musculature and the full transformation of the beak.}, } @article {pmid29720635, year = {2018}, author = {Zhang, L and Bailey, JB and Subramanian, RH and Groisman, A and Tezcan, FA}, title = {Hyperexpandable, self-healing macromolecular crystals with integrated polymer networks.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {86-91}, doi = {10.1038/s41586-018-0057-7}, pmid = {29720635}, issn = {1476-4687}, support = {T32 GM112584/GM/NIGMS NIH HHS/United States ; }, abstract = {The formation of condensed matter typically involves a trade-off between structural order and flexibility. As the extent and directionality of interactions between atomic or molecular components increase, materials generally become more ordered but less compliant, and vice versa. Nevertheless, high levels of structural order and flexibility are not necessarily mutually exclusive; there are many biological (such as microtubules1,2, flagella 3 , viruses4,5) and synthetic assemblies (for example, dynamic molecular crystals6-9 and frameworks10-13) that can undergo considerable structural transformations without losing their crystalline order and that have remarkable mechanical properties8,14,15 that are useful in diverse applications, such as selective sorption 16 , separation 17 , sensing 18 and mechanoactuation 19 . However, the extent of structural changes and the elasticity of such flexible crystals are constrained by the necessity to maintain a continuous network of bonding interactions between the constituents of the lattice. Consequently, even the most dynamic porous materials tend to be brittle and isolated as microcrystalline powders 14 , whereas flexible organic or inorganic molecular crystals cannot expand without fracturing. Owing to their rigidity, crystalline materials rarely display self-healing behaviour 20 . Here we report that macromolecular ferritin crystals with integrated hydrogel polymers can isotropically expand to 180 per cent of their original dimensions and more than 500 per cent of their original volume while retaining periodic order and faceted Wulff morphologies. Even after the separation of neighbouring ferritin molecules by 50 ångströms upon lattice expansion, specific molecular contacts between them can be reformed upon lattice contraction, resulting in the recovery of atomic-level periodicity and the highest-resolution ferritin structure reported so far. Dynamic bonding interactions between the hydrogel network and the ferritin molecules endow the crystals with the ability to resist fragmentation and self-heal efficiently, whereas the chemical tailorability of the ferritin molecules enables the creation of chemically and mechanically differentiated domains within single crystals.}, } @article {pmid29720634, year = {2018}, author = {Rivron, NC and Frias-Aldeguer, J and Vrij, EJ and Boisset, JC and Korving, J and Vivié, J and Truckenmüller, RK and van Oudenaarden, A and van Blitterswijk, CA and Geijsen, N}, title = {Blastocyst-like structures generated solely from stem cells.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {106-111}, doi = {10.1038/s41586-018-0051-0}, pmid = {29720634}, issn = {1476-4687}, mesh = {Animals ; Blastocyst/*cytology/metabolism ; Bone Morphogenetic Protein 4/pharmacology ; Cell Self Renewal ; Ectoderm/cytology/metabolism ; Embryo Implantation ; Embryonic Stem Cells/*cytology/metabolism ; Female ; Gene Expression Regulation, Developmental ; Humans ; Kruppel-Like Factor 6/deficiency/genetics/metabolism ; Male ; Mice ; Morphogenesis ; Nodal Protein/genetics/metabolism/pharmacology ; Transcriptome ; Trophoblasts/cytology/metabolism ; Uterus/cytology/metabolism ; }, abstract = {The blastocyst (the early mammalian embryo) forms all embryonic and extra-embryonic tissues, including the placenta. It consists of a spherical thin-walled layer, known as the trophectoderm, that surrounds a fluid-filled cavity sheltering the embryonic cells 1 . From mouse blastocysts, it is possible to derive both trophoblast 2 and embryonic stem-cell lines 3 , which are in vitro analogues of the trophectoderm and embryonic compartments, respectively. Here we report that trophoblast and embryonic stem cells cooperate in vitro to form structures that morphologically and transcriptionally resemble embryonic day 3.5 blastocysts, termed blastoids. Like blastocysts, blastoids form from inductive signals that originate from the inner embryonic cells and drive the development of the outer trophectoderm. The nature and function of these signals have been largely unexplored. Genetically and physically uncoupling the embryonic and trophectoderm compartments, along with single-cell transcriptomics, reveals the extensive inventory of embryonic inductions. We specifically show that the embryonic cells maintain trophoblast proliferation and self-renewal, while fine-tuning trophoblast epithelial morphogenesis in part via a BMP4/Nodal-KLF6 axis. Although blastoids do not support the development of bona fide embryos, we demonstrate that embryonic inductions are crucial to form a trophectoderm state that robustly implants and triggers decidualization in utero. Thus, at this stage, the nascent embryo fuels trophectoderm development and implantation.}, } @article {pmid29720633, year = {2018}, author = {Langer, F and Schmid, CP and Schlauderer, S and Gmitra, M and Fabian, J and Nagler, P and Schüller, C and Korn, T and Hawkins, PG and Steiner, JT and Huttner, U and Koch, SW and Kira, M and Huber, R}, title = {Lightwave valleytronics in a monolayer of tungsten diselenide.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {76-80}, pmid = {29720633}, issn = {1476-4687}, support = {305003//European Research Council/International ; }, abstract = {As conventional electronics approaches its limits 1 , nanoscience has urgently sought methods of fast control of electrons at the fundamental quantum level 2 . Lightwave electronics 3 -the foundation of attosecond science 4 -uses the oscillating carrier wave of intense light pulses to control the translational motion of the electron's charge faster than a single cycle of light5-15. Despite being particularly promising information carriers, the internal quantum attributes of spin 16 and valley pseudospin17-21 have not been switchable on the subcycle scale. Here we demonstrate lightwave-driven changes of the valley pseudospin and introduce distinct signatures in the optical readout. Photogenerated electron-hole pairs in a monolayer of tungsten diselenide are accelerated and collided by a strong lightwave. The emergence of high-odd-order sidebands and anomalous changes in their polarization direction directly attest to the ultrafast pseudospin dynamics. Quantitative computations combining density functional theory with a non-perturbative quantum many-body approach assign the polarization of the sidebands to a lightwave-induced change of the valley pseudospin and confirm that the process is coherent and adiabatic. Our work opens the door to systematic valleytronic logic at optical clock rates.}, } @article {pmid29720632, year = {2018}, author = {Spake, JJ and Sing, DK and Evans, TM and Oklopčić, A and Bourrier, V and Kreidberg, L and Rackham, BV and Irwin, J and Ehrenreich, D and Wyttenbach, A and Wakeford, HR and Zhou, Y and Chubb, KL and Nikolov, N and Goyal, JM and Henry, GW and Williamson, MH and Blumenthal, S and Anderson, DR and Hellier, C and Charbonneau, D and Udry, S and Madhusudhan, N}, title = {Helium in the eroding atmosphere of an exoplanet.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {68-70}, doi = {10.1038/s41586-018-0067-5}, pmid = {29720632}, issn = {1476-4687}, abstract = {Helium is the second-most abundant element in the Universe after hydrogen and is one of the main constituents of gas-giant planets in our Solar System. Early theoretical models predicted helium to be among the most readily detectable species in the atmospheres of exoplanets, especially in extended and escaping atmospheres 1 . Searches for helium, however, have hitherto been unsuccessful 2 . Here we report observations of helium on an exoplanet, at a confidence level of 4.5 standard deviations. We measured the near-infrared transmission spectrum of the warm gas giant 3 WASP-107b and identified the narrow absorption feature of excited metastable helium at 10,833 angstroms. The amplitude of the feature, in transit depth, is 0.049 ± 0.011 per cent in a bandpass of 98 angstroms, which is more than five times greater than what could be caused by nominal stellar chromospheric activity. This large absorption signal suggests that WASP-107b has an extended atmosphere that is eroding at a total rate of 1010 to 3 × 1011 grams per second (0.1-4 per cent of its total mass per billion years), and may have a comet-like tail of gas shaped by radiation pressure.}, } @article {pmid29720443, year = {2018}, author = {Bayliss, SL and Weiss, LR and Mitioglu, A and Galkowski, K and Yang, Z and Yunusova, K and Surrente, A and Thorley, KJ and Behrends, J and Bittl, R and Anthony, JE and Rao, A and Friend, RH and Plochocka, P and Christianen, PCM and Greenham, NC and Chepelianskii, AD}, title = {Site-selective measurement of coupled spin pairs in an organic semiconductor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5077-5082}, pmid = {29720443}, issn = {1091-6490}, abstract = {From organic electronics to biological systems, understanding the role of intermolecular interactions between spin pairs is a key challenge. Here we show how such pairs can be selectively addressed with combined spin and optical sensitivity. We demonstrate this for bound pairs of spin-triplet excitations formed by singlet fission, with direct applicability across a wide range of synthetic and biological systems. We show that the site sensitivity of exchange coupling allows distinct triplet pairs to be resonantly addressed at different magnetic fields, tuning them between optically bright singlet ([Formula: see text]) and dark triplet quintet ([Formula: see text]) configurations: This induces narrow holes in a broad optical emission spectrum, uncovering exchange-specific luminescence. Using fields up to 60 T, we identify three distinct triplet-pair sites, with exchange couplings varying over an order of magnitude (0.3-5 meV), each with its own luminescence spectrum, coexisting in a single material. Our results reveal how site selectivity can be achieved for organic spin pairs in a broad range of systems.}, } @article {pmid29720442, year = {2018}, author = {Dias, AM and Correia, A and Pereira, MS and Almeida, CR and Alves, I and Pinto, V and Catarino, TA and Mendes, N and Leander, M and Oliva-Teles, MT and Maia, L and Delerue-Matos, C and Taniguchi, N and Lima, M and Pedroto, I and Marcos-Pinto, R and Lago, P and Reis, CA and Vilanova, M and Pinho, SS}, title = {Metabolic control of T cell immune response through glycans in inflammatory bowel disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4651-E4660}, pmid = {29720442}, issn = {1091-6490}, mesh = {Acetylglucosamine/*pharmacology ; Adaptive Immunity ; Animals ; CD4-Positive T-Lymphocytes/drug effects/*immunology/metabolism ; Case-Control Studies ; Colitis, Ulcerative/chemically induced/drug therapy/*immunology/metabolism ; Cytokines/metabolism ; Glycosylation ; Humans ; Lymphocyte Activation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; N-Acetylglucosaminyltransferases/*physiology ; Polysaccharides/*metabolism ; Receptors, Antigen, T-Cell/metabolism ; }, abstract = {Mucosal T lymphocytes from patients with ulcerative colitis (UC) were previously shown to display a deficiency in branched N-glycosylation associated with disease severity. However, whether this glycosylation pathway shapes the course of the T cell response constituting a targeted-specific mechanism in UC remains largely unknown. In this study, we demonstrated that metabolic supplementation of ex vivo mucosal T cells from patients with active UC with N-acetylglucosamine (GlcNAc) resulted in enhancement of branched N-glycosylation in the T cell receptor (TCR), leading to suppression of T cell growth, inhibition of the T helper 1 (Th1)/Th17 immune response, and controlled T cell activity. We further demonstrated that mouse models displaying a deficiency in the branched N-glycosylation pathway (MGAT5-/-, MGAT5+/-) exhibited increased susceptibility to severe forms of colitis and early-onset disease. Importantly, the treatment of these mice with GlcNAc reduced disease severity and suppressed disease progression due to a controlled T cell-mediated immune response at the intestinal mucosa. In conclusion, our human ex vivo and preclinical results demonstrate the targeted-specific immunomodulatory properties of this simple glycan, proposing a therapeutic approach for patients with UC.}, } @article {pmid29720279, year = {2018}, author = {Chikowe, I and Mwapasa, V and Kengne, AP}, title = {Analysis of rural health centres preparedness for the management of diabetic patients in Malawi.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {267}, pmid = {29720279}, issn = {1756-0500}, mesh = {Diabetes Mellitus/*diagnosis/*therapy ; Humans ; Malawi ; Rural Health Services/*standards/*statistics & numerical data ; }, abstract = {OBJECTIVE: There is limited data on the quality of primary care management for diabetes mellitus across Africa. The study was aimed at assessing the availability of basic supplies for the rapid diagnosis, treatment and management of diabetes in Malawian rural health facilities. This cross-sectional study was conducted in 55 public and private health centers from 19 districts using a structured questionnaire and checklist to interview the pharmacy personnel or officer in-charge of the health centers. We focused on availability of information, diagnosis and treatment materials for diabetes.

RESULTS: Of the 55 health facilities surveyed, 21, 23 and 11 were located in the central, southern and northern regions of Malawi, respectively. Overall, 38% (21/55) of the health centres had glucometers, while 24% (13/55) had urine glucose dipsticks. Only 4% (2/55) of the health centres had recommended first-line medicines for treatment of type 1 and type 2 diabetes. No health centre had diabetes patient records and information, education and communication materials. Most rural health centers in Malawi lack basic health commodities for the screening, diagnosis and treatment of diabetes and this impedes on their effective management of growing diabetes burden. Therefore, health care systems need to adequately equip primary care facilities.}, } @article {pmid29720271, year = {2018}, author = {Fietz, K and Rye Hintze, CO and Skovrind, M and Kjærgaard Nielsen, T and Limborg, MT and Krag, MA and Palsbøll, PJ and Hestbjerg Hansen, L and Rask Møller, P and Gilbert, MTP}, title = {Mind the gut: genomic insights to population divergence and gut microbial composition of two marine keystone species.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {82}, pmid = {29720271}, issn = {2049-2618}, mesh = {Animals ; *Bacteria/classification/genetics/isolation & purification ; Base Sequence ; Fishes/*microbiology ; Gastrointestinal Microbiome/*genetics ; Genetics, Population ; Genome, Bacterial/*genetics ; Oceans and Seas ; Polymorphism, Single Nucleotide/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Deciphering the mechanisms governing population genetic divergence and local adaptation across heterogeneous environments is a central theme in marine ecology and conservation. While population divergence and ecological adaptive potential are classically viewed at the genetic level, it has recently been argued that their microbiomes may also contribute to population genetic divergence. We explored whether this might be plausible along the well-described environmental gradient of the Baltic Sea in two species of sand lance (Ammodytes tobianus and Hyperoplus lanceolatus). Specifically, we assessed both their population genetic and gut microbial composition variation and investigated not only which environmental parameters correlate with the observed variation, but whether host genome also correlates with microbiome variation.

RESULTS: We found a clear genetic structure separating the high-salinity North Sea from the low-salinity Baltic Sea sand lances. The observed genetic divergence was not simply a function of isolation by distance, but correlated with environmental parameters, such as salinity, sea surface temperature, and, in the case of A. tobianus, possibly water microbiota. Furthermore, we detected two distinct genetic groups in Baltic A. tobianus that might represent sympatric spawning types. Investigation of possible drivers of gut microbiome composition variation revealed that host species identity was significantly correlated with the microbial community composition of the gut. A potential influence of host genetic factors on gut microbiome composition was further confirmed by the results of a constrained analysis of principal coordinates. The host genetic component was among the parameters that best explain observed variation in gut microbiome composition.

CONCLUSIONS: Our findings have relevance for the population structure of two commercial species but also provide insights into potentially relevant genomic and microbial factors with regards to sand lance adaptation across the North Sea-Baltic Sea environmental gradient. Furthermore, our findings support the hypothesis that host genetics may play a role in regulating the gut microbiome at both the interspecific and intraspecific levels. As sequencing costs continue to drop, we anticipate that future studies that include full genome and microbiome sequencing will be able to explore the full relationship and its potential adaptive implications for these species.}, } @article {pmid29720270, year = {2018}, author = {Aghazadeh-Attari, J and Mobaraki, K and Ahmadzadeh, J and Mansorian, B and Mohebbi, I}, title = {Quality of observational studies in prestigious journals of occupational medicine and health based on Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) Statement: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {266}, pmid = {29720270}, issn = {1756-0500}, support = {2183//Urmia University Medical Sciences/ ; }, mesh = {*Bibliometrics ; Biomedical Research/*standards ; Cross-Sectional Studies ; Epidemiology/*standards ; Humans ; Observational Studies as Topic/*standards ; Occupational Health/*standards ; Occupational Medicine/*standards ; Periodicals as Topic/*standards ; Reproducibility of Results ; }, abstract = {OBJECTIVE: The present study applied the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement to observational studies published in prestigious occupational medicine and health journals.

RESULTS: A total of 60 articles was evaluated. All sub-items were reported in 63.74% (95% confidence interval [CI], 56.24-71.24%), not reported in 29.70% (95% CI, 20.2-39.2%), and not applicable in 6.56% (95% CI, 4.86-8.26%) of the studies. Of the 45 sub-items investigated in this survey, eight were reported 100% of the time, 13 were addressed in more than 90% of the articles, 22 were included in more than 75% of the studies, and 27 sub-items were applied in more than 50% of the articles published in the journals included in this study.}, } @article {pmid29720254, year = {2018}, author = {Gupta, N and Duggal, S and Kumar, A and Saquib, NM and Rao, KVS}, title = {Concurrent interactome and metabolome analysis reveals role of AKT1 in central carbon metabolism.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {270}, pmid = {29720254}, issn = {1756-0500}, mesh = {Acetyl Coenzyme A/*metabolism ; Carbon/*metabolism ; HEK293 Cells ; Humans ; Metabolic Networks and Pathways/*physiology ; Metabolome/*physiology ; Metabolomics/*methods ; Protein Interaction Maps/*physiology ; Proteomics/*methods ; Proto-Oncogene Proteins c-akt/*metabolism ; Pyruvate Dehydrogenase Complex/*metabolism ; }, abstract = {OBJECTIVE: Signal transduction not only initiates entry into the cell cycle, but also reprograms the cell's metabolism. To control abnormalities in cell proliferation, both the aspects should be taken care of, thus pleiotropic signaling molecules are considered as crucial modulators. Considering this, we investigated the role of AKT1 in central carbon metabolism. The role of AKT1 has already been established in the process of cell cycle, but its contribution to the central carbon metabolism is sparsely studied.

RESULTS: To address this, we combined the metabolomics and proteomics approaches. In accordance to our hypothesis, we found that the AKT1 kinase activity is regulating the levels of acetyl CoA through pyruvate dehydrogenase complex. Further, the decreased levels of acetyl CoA and dependency of acetyl CoA acetyl transferase protein on AKT1 kinase activity was also found to perturb the synthesis rate of palmitic acid which is a representative of fatty acid. This was analyzed in the present study using lipid labeling method through mass spectrometry.}, } @article {pmid29720253, year = {2018}, author = {Phenwan, T}, title = {Relieving total pain in an adolescent: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {265}, pmid = {29720253}, issn = {1756-0500}, mesh = {Adolescent ; Humans ; *Lymphoma, T-Cell ; Male ; *Pain/diagnosis/physiopathology/psychology ; Pain Management/*methods ; Palliative Care/*methods ; Thailand ; }, abstract = {BACKGROUND: Total pain is a concept that approaches pain holistically: physically, psychologically, socially, and spiritually. Any individual may experience pain in each domain at a different level. This is the case report of an adolescent who suffered from total pain and how his healthcare team and peers helped to relieve it.

CASE PRESENTATION: A 15-years-old Thai male was diagnosed with recurrent T-cell lymphoma and readmitted to hospital. He was admitted to an adult ward and suffered from pain due to his disease and from the fear of being alienated. As a result, he had an existential crisis. His parents felt unsure whether they or the patient should make the medical decisions and advance care plan.

CONCLUSIONS: This case report emphasises the importance of total pain assessment in the relief of total pain in an adolescent whose needs are different from both children and adults. It also highlights the role of medical decision-making in adolescents and the importance of the social support of peers in the alleviation of pain.}, } @article {pmid29720242, year = {2018}, author = {Ruymbeke, H and Harlet, L and Stragier, B and Steenkiste, E and Ryckx, M and Marolleau, F}, title = {Anorectal metastasis from breast carcinoma: a case report and review of the literature.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {268}, pmid = {29720242}, issn = {1756-0500}, mesh = {Aged ; Anus Neoplasms/secondary ; Breast Neoplasms/*pathology ; Carcinoma, Lobular/*pathology ; Female ; Humans ; Neoplasm Metastasis ; Rectal Neoplasms/*secondary ; }, abstract = {BACKGROUND: Gastrointestinal metastasis from primary breast carcinoma is uncommon, anorectal involvement is extremely rare.

CASE PRESENTATION: We present the case of a 65-year old woman who underwent treatment for an infiltrative lobular carcinoma of the left breast with bone metastases and who developed metastasis of the rectum and anal canal 4 years later.

CONCLUSIONS: A patient with a history of breast cancer, especially lobular carcinoma, presenting with anorectal symptoms, should raise the suspicion of metastatic disease.}, } @article {pmid29720217, year = {2018}, author = {de Araújo, PSR and de Souza Junior, VR and de Souza, A and de Barros Correia Fontes, L and Brandao, E and Rocha, A}, title = {Chiluria in a lymphatic filariasis endemic area.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {269}, pmid = {29720217}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Animals ; Brazil ; Elephantiasis, Filarial/complications/parasitology/*urine ; Endemic Diseases ; Female ; Humans ; Male ; Middle Aged ; Retrospective Studies ; Urination Disorders/etiology/*urine ; Wuchereria bancrofti/*pathogenicity ; Young Adult ; }, abstract = {OBJECTIVE: To establish clinical and laboratory data of individuals presenting chyluria in endemic areas.

RESULTS: 75 individuals were studied. The majority were females with an average age of 45 years residing in the Metropolitan Region of Recife. The mean time between the beginning of the presentation of chyluria and the first care service in the Serviço de Referencia Nacional em Filarioses was approximately 5 years. The most frequent urinalysis changes were hematuria (27.6%), leukocytes (21.9%) and proteinuria (10.5%). The Addis test showed mean values of 155.43 E/min/mL of cylinders, 52,892 E/min/mL of erythrocytes and 291,660 E/min/mL of leukocytes. Among recorded cases, proteinuria had a mean value of 1372.80 mg/dL in 24 h, and the presence of lymphocytes in the urine was positive in 68.3%. Among lymphatic filariasis tests, immunochromatography was positive in 16.7%, there was circulating filarial antigen determined by detection of OG4C3 antibodies in 7.7% and microfilaremia in only 1/55.}, } @article {pmid29720174, year = {2018}, author = {Danson, AF and Marzi, SJ and Lowe, R and Holland, ML and Rakyan, VK}, title = {Early life diet conditions the molecular response to post-weaning protein restriction in the mouse.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {51}, pmid = {29720174}, issn = {1741-7007}, support = {MR/K501372/1//Medical Research Council/United Kingdom ; BB/M012494/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Environmental influences fluctuate throughout the life course of an organism. It is therefore important to understand how the timing of exposure impacts molecular responses. Herein, we examine the responses of two key molecular markers of dietary stress, namely variant-specific methylation at ribosomal DNA (rDNA) and small RNA distribution, including tRNA fragments, in a mouse model of protein restriction (PR) with exposure at pre- and/or post-weaning.

RESULTS: We first confirm that pre-weaning PR exposure modulates the methylation state of rDNA in a genotype-dependent manner, whereas post-weaning PR exposure has no such effect. Conversely, post-weaning PR induces a shift in small RNA distribution, but there is no effect in the pre-weaning PR model. Intriguingly, mice exposed to PR throughout their lives show neither of these two dietary stress markers, similar to controls.

CONCLUSIONS: The results show that the timing of the insult affects the nature of the molecular response but also, critically, that 'matching' diet exposure either side of weaning eliminates the stress response at the level of rDNA methylation and small RNA in sperm.}, } @article {pmid29720106, year = {2018}, author = {Zhang, D and Hu, P and Liu, T and Wang, J and Jiang, S and Xu, Q and Chen, L}, title = {GC bias lead to increased small amino acids and random coils of proteins in cold-water fishes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {315}, pmid = {29720106}, issn = {1471-2164}, support = {31572611//National Natural Science Foundation of China/ ; 41761134050//National Natural Science Foundation of China/ ; 2017-01-07-00-10-E00060//the Major Science Innovation Grant/ ; }, mesh = {Amino Acid Sequence ; Amino Acid Substitution ; Animals ; *Cold Temperature ; Fish Proteins/*chemistry/*genetics ; Fishes/*genetics ; *GC Rich Sequence ; Protein Structure, Secondary/genetics ; Sequence Alignment ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Temperature adaptation of biological molecules is fundamental in evolutionary studies but remains unsolved. Fishes living in cold water are adapted to low temperatures through adaptive modification of their biological molecules, which enables their functioning in extreme cold. To study nucleotide and amino acid preference in cold-water fishes, we investigated the substitution asymmetry of codons and amino acids in protein-coding DNA sequences between cold-water fishes and tropical fishes., The former includes two Antarctic fishes, Dissostichus mawsoni (Antarctic toothfish), Gymnodraco acuticeps (Antarctic dragonfish), and two temperate fishes, Gadus morhua (Atlantic cod) and Gasterosteus aculeatus (stickleback), and the latter includes three tropical fishes, including Danio rerio (zebrafish), Oreochromis niloticus (Nile tilapia) and Xiphophorus maculatus (Platyfish).

RESULTS: Cold-water fishes showed preference for Guanines and cytosines (GCs) in both synonymous and nonsynonymous codon substitution when compared with tropical fishes. Amino acids coded by GC-rich codons are favored in the temperate fishes, while those coded by AT-rich codons are disfavored. Similar trends were discovered in Antarctic fishes but were statistically weaker. The preference of GC rich codons in nonsynonymous substitution tends to increase ratio of small amino acid in proteins, which was demonstrated by biased small amino acid substitutions in the cold-water species when compared with the tropical species, especially in the temperate species. Prediction and comparison of secondary structure of the proteomes showed that frequency of random coils are significantly larger in the cold-water fish proteomes than those of the tropical fishes.

CONCLUSIONS: Our results suggested that natural selection in cold temperature might favor biased GC content in the coding DNA sequences, which lead to increased frequency of small amino acids and consequently increased random coils in the proteomes of cold-water fishes.}, } @article {pmid29720105, year = {2018}, author = {Wang, K and Bai, ZY and Liang, QY and Liu, QL and Zhang, L and Pan, YZ and Liu, GL and Jiang, BB and Zhang, F and Jia, Y}, title = {Transcriptome analysis of chrysanthemum (Dendranthema grandiflorum) in response to low temperature stress.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {319}, pmid = {29720105}, issn = {1471-2164}, support = {31201649//National Natural Science Foundation of China/ ; }, mesh = {Acclimatization/genetics ; Cell Membrane/metabolism ; Chrysanthemum/cytology/*genetics/metabolism/*physiology ; Cold-Shock Response/*genetics ; *Gene Expression Profiling ; Molecular Sequence Annotation ; Osmosis ; Phenotype ; Plant Growth Regulators/metabolism ; Protein Kinases/metabolism ; Sequence Analysis ; Signal Transduction/genetics ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: Chrysanthemum is one kind of ornamental plant well-known and widely used in the world. However, its quality and production were severely affected by low temperature conditions in winter and early spring periods. Therefore, we used the RNA-Seq platform to perform a de novo transcriptome assembly to analyze chrysanthemum (Dendranthema grandiflorum) transcription response to low temperature.

RESULTS: Using Illumina sequencing technology, a total of 86,444,237 high-quality clean reads and 93,837 unigenes were generated from four libraries: T01, controls; T02, 4 °C cold acclimation (CA) for 24 h; T03, - 4 °C freezing treatments for 4 h with prior CA; and T04, - 4 °C freezing treatments for 4 h without prior CA. In total, 7583 differentially expressed genes (DEGs) of 36,462 annotated unigenes were identified. We performed GO and KEGG pathway enrichment analyses, and excavated a group of important cold-responsive genes related to low temperature sensing and signal transduction, membrane lipid stability, reactive oxygen species (ROS) scavenging and osmoregulation. These genes encode many key proteins in plant biological processes, such as protein kinases, transcription factors, fatty acid desaturase, lipid-transfer proteins, antifreeze proteins, antioxidase and soluble sugars synthetases. We also verified expression levels of 10 DEGs using quantitative real-time polymerase chain reaction (qRT-PCR). In addition, we performed the determination of physiological indicators of chrysanthemum treated at low temperature, and the results were basically consistent with molecular sequencing results.

CONCLUSION: In summary, our study presents a genome-wide transcript profile of Dendranthema grandiflorum var. jinba and provides insights into the molecular mechanisms of D. grandiflorum in response to low temperature. These data contributes to our deeper relevant researches on cold tolerance and further exploring new candidate genes for chilling-tolerance and freezing-tolerance chrysanthemum molecular breeding.}, } @article {pmid29720103, year = {2018}, author = {Simopoulos, CMA and Weretilnyk, EA and Golding, GB}, title = {Prediction of plant lncRNA by ensemble machine learning classifiers.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {316}, pmid = {29720103}, issn = {1471-2164}, support = {RGPIN-2015-04477//Natural Sciences and Engineering Research Council of Canada/ ; RGPIN-2015-06530//Ontario Research Fund-Research Excellence/ ; }, mesh = {Computational Biology/*methods ; *Machine Learning ; Open Reading Frames/genetics ; RNA, Long Noncoding/*genetics ; RNA, Plant/genetics ; Stochastic Processes ; }, abstract = {BACKGROUND: In plants, long non-protein coding RNAs are believed to have essential roles in development and stress responses. However, relative to advances on discerning biological roles for long non-protein coding RNAs in animal systems, this RNA class in plants is largely understudied. With comparatively few validated plant long non-coding RNAs, research on this potentially critical class of RNA is hindered by a lack of appropriate prediction tools and databases. Supervised learning models trained on data sets of mostly non-validated, non-coding transcripts have been previously used to identify this enigmatic RNA class with applications largely focused on animal systems. Our approach uses a training set comprised only of empirically validated long non-protein coding RNAs from plant, animal, and viral sources to predict and rank candidate long non-protein coding gene products for future functional validation.

RESULTS: Individual stochastic gradient boosting and random forest classifiers trained on only empirically validated long non-protein coding RNAs were constructed. In order to use the strengths of multiple classifiers, we combined multiple models into a single stacking meta-learner. This ensemble approach benefits from the diversity of several learners to effectively identify putative plant long non-coding RNAs from transcript sequence features. When the predicted genes identified by the ensemble classifier were compared to those listed in GreeNC, an established plant long non-coding RNA database, overlap for predicted genes from Arabidopsis thaliana, Oryza sativa and Eutrema salsugineum ranged from 51 to 83% with the highest agreement in Eutrema salsugineum. Most of the highest ranking predictions from Arabidopsis thaliana were annotated as potential natural antisense genes, pseudogenes, transposable elements, or simply computationally predicted hypothetical protein. Due to the nature of this tool, the model can be updated as new long non-protein coding transcripts are identified and functionally verified.

CONCLUSIONS: This ensemble classifier is an accurate tool that can be used to rank long non-protein coding RNA predictions for use in conjunction with gene expression studies. Selection of plant transcripts with a high potential for regulatory roles as long non-protein coding RNAs will advance research in the elucidation of long non-protein coding RNA function.}, } @article {pmid29720102, year = {2018}, author = {Elliott, M and Yuzon, J and C, MM and Tripathy, S and Bui, M and Chastagner, GA and Coats, K and Rizzo, DM and Garbelotto, M and Kasuga, T}, title = {Characterization of phenotypic variation and genome aberrations observed among Phytophthora ramorum isolates from diverse hosts.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {320}, pmid = {29720102}, issn = {1471-2164}, support = {5306-22000-014-00D//Agricultural Research Service/ ; 10201//Animal and Plant Health Inspection Service/ ; 10201//Animal and Plant Health Inspection Service/ ; 10201//Animal and Plant Health Inspection Service/ ; 10201//Animal and Plant Health Inspection Service/ ; 10007//Animal and Plant Health Inspection Service/ ; 10007//Animal and Plant Health Inspection Service/ ; 10007//Animal and Plant Health Inspection Service/ ; 10007//Animal and Plant Health Inspection Service/ ; 12-8130-0191-CA//Animal and Plant Health Inspection Service/ ; 10201//Animal and Plant Health Inspection Service/ ; 10201//Animal and Plant Health Inspection Service/ ; 10007//Animal and Plant Health Inspection Service/ ; 10007//Animal and Plant Health Inspection Service/ ; 12-8130-0191-CA//Animal and Plant Health Inspection Service/ ; 12-8130-0191-CA//Animal and Plant Health Inspection Service/ ; }, mesh = {*Chromosome Aberrations ; DNA Copy Number Variations ; *Genomics ; Haplotypes ; *Host-Parasite Interactions ; *Phenotype ; Phytophthora/*genetics/physiology ; Umbellularia/parasitology ; }, abstract = {BACKGROUND: Accumulating evidence suggests that genome plasticity allows filamentous plant pathogens to adapt to changing environments. Recently, the generalist plant pathogen Phytophthora ramorum has been documented to undergo irreversible phenotypic alterations accompanied by chromosomal aberrations when infecting trunks of mature oak trees (genus Quercus). In contrast, genomes and phenotypes of the pathogen derived from the foliage of California bay (Umbellularia californica) are usually stable. We define this phenomenon as host-induced phenotypic diversification (HIPD). P. ramorum also causes a severe foliar blight in some ornamental plants such as Rhododendron spp. and Viburnum spp., and isolates from these hosts occasionally show phenotypes resembling those from oak trunks that carry chromosomal aberrations. The aim of this study was to investigate variations in phenotypes and genomes of P. ramorum isolates from non-oak hosts and substrates to determine whether HIPD changes may be equivalent to those among isolates from oaks.

RESULTS: We analyzed genomes of diverse non-oak isolates including those taken from foliage of Rhododendron and other ornamental plants, as well as from natural host species, soil, and water. Isolates recovered from artificially inoculated oak logs were also examined. We identified diverse chromosomal aberrations including copy neutral loss of heterozygosity (cnLOH) and aneuploidy in isolates from non-oak hosts. Most identified aberrations in non-oak hosts were also common among oak isolates; however, trisomy, a frequent type of chromosomal aberration in oak isolates was not observed in isolates from Rhododendron.

CONCLUSION: This work cross-examined phenotypic variation and chromosomal aberrations in P. ramorum isolates from oak and non-oak hosts and substrates. The results suggest that HIPD comparable to that occurring in oak hosts occurs in non-oak environments such as in Rhododendron leaves. Rhododendron leaves are more easily available than mature oak stems and thus can potentially serve as a model host for the investigation of HIPD, the newly described plant-pathogen interaction.}, } @article {pmid29720089, year = {2018}, author = {Olwal, CO and Ang'ienda, PO and Onyango, DM and Ochiel, DO}, title = {Susceptibility patterns and the role of extracellular DNA in Staphylococcus epidermidis biofilm resistance to physico-chemical stress exposure.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {40}, pmid = {29720089}, issn = {1471-2180}, abstract = {BACKGROUND: Over 65% of human infections are ascribed to bacterial biofilms that are often highly resistant to antibiotics and host immunity. Staphylococcus epidermidis is the predominant cause of recurrent nosocomial and biofilm-related infections. However, the susceptibility patterns of S. epidermidis biofilms to physico-chemical stress induced by commonly recommended disinfectants [(heat, sodium chloride (NaCl), sodium hypochlorite (NaOCl) and hydrogen peroxide (H2O2)] in domestic and human healthcare settings remains largely unknown. Further, the molecular mechanisms of bacterial biofilms resistance to the physico-chemical stresses remain unclear. Growing evidence demonstrates that extracellular DNA (eDNA) protects bacterial biofilms against antibiotics. However, the role of eDNA as a potential mechanism underlying S. epidermidis biofilms resistance to physico-chemical stress exposure is yet to be understood. Therefore, this study aimed to evaluate the susceptibility patterns of and eDNA release by S. epidermidis biofilm and planktonic cells to physico-chemical stress exposure.

RESULTS: S. epidermidis biofilms exposed to physico-chemical stress conditions commonly recommended for disinfection [heat (60 °C), 1.72 M NaCl, solution containing 150 μL of waterguard (0.178 M NaOCl) in 1 L of water or 1.77 M H2O2] for 30 and 60 min exhibited lower log reductions of CFU/mL than the corresponding planktonic cells (p < 0.0001). The eDNA released by sub-lethal heat (50 °C)-treated S. epidermidis biofilm and planktonic cells was not statistically different (p = 0.8501). However, 50 °C-treated S. epidermidis biofilm cells released significantly increased eDNA than the untreated controls (p = 0.0098). The eDNA released by 0.8 M NaCl-treated S. epidermidis biofilm and planktonic cells was not significantly different (p = 0.9697). Conversely, 5 mM NaOCl-treated S. epidermidis biofilms exhibited significantly increased eDNA release than the corresponding planktonic cells (p = 0.0015). Further, the 50 μM H2O2-treated S. epidermidis biofilms released significantly more eDNA than the corresponding planktonic cells (p = 0.021).

CONCLUSIONS: S. epidermidis biofilms were less susceptible to physico-chemical stress induced by the four commonly recommended disinfectants than the analogous planktonic cells. Further, S. epidermidis biofilms enhanced eDNA release in response to the sub-lethal heat and oxidative stress exposure than the corresponding planktonic cells suggesting a role of eDNA in biofilms resistance to the physico-chemical stresses.}, } @article {pmid29720087, year = {2018}, author = {Janská, A and Svoboda, P and Spiwok, V and Kučera, L and Ovesná, J}, title = {The dehydration stress of couch grass is associated with its lipid metabolism, the induction of transporters and the re-programming of development coordinated by ABA.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {317}, pmid = {29720087}, issn = {1471-2164}, support = {QH81287 and QJ1310055//Czech National Agency for Agricultural Research/ ; LO1417//Czech ministry of Education Youth and Sports/ ; MSMT 20/2015//Specific University Research/ ; RO0417//Czech Ministry of Agriculture/ ; }, mesh = {Abscisic Acid/*metabolism ; *Droughts ; Electrolytes/metabolism ; Gene Expression Profiling ; Lipid Metabolism/*genetics ; Membrane Transport Proteins/*genetics ; Poaceae/*genetics/metabolism/*physiology ; Stress, Physiological/*genetics ; Water/metabolism ; }, abstract = {BACKGROUND: The wild relatives of crop species represent a potentially valuable source of novel genetic variation, particularly in the context of improving the crop's level of tolerance to abiotic stress. The mechanistic basis of these tolerances remains largely unexplored. Here, the focus was to characterize the transcriptomic response of the nodes (meristematic tissue) of couch grass (a relative of barley) to dehydration stress, and to compare it to that of the barley crown formed by both a drought tolerant and a drought sensitive barley cultivar.

RESULTS: Many of the genes up-regulated in the nodes by the stress were homologs of genes known to be mediated by abscisic acid during the response to drought, or were linked to either development or lipid metabolism. Transporters also featured prominently, as did genes acting on root architecture. The resilience of the couch grass node arise from both their capacity to develop an altered, more effective root architecture, but also from their formation of a lipid barrier on their outer surface and their ability to modify both their lipid metabolism and transporter activity when challenged by dehydration stress.

CONCLUSIONS: Our analysis revealed the nature of dehydration stress response in couch grass. We suggested the tolerance is associated with lipid metabolism, the induction of transporters and the re-programming of development coordinated by ABA. We also proved the applicability of barley microarray for couch grass stress-response analysis.}, } @article {pmid29720086, year = {2018}, author = {Miyasaka, Y and Uno, Y and Yoshimi, K and Kunihiro, Y and Yoshimura, T and Tanaka, T and Ishikubo, H and Hiraoka, Y and Takemoto, N and Tanaka, T and Ooguchi, Y and Skehel, P and Aida, T and Takeda, J and Mashimo, T}, title = {CLICK: one-step generation of conditional knockout mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {318}, pmid = {29720086}, issn = {1471-2164}, support = {26290033//Japan Society for the Promotion of Science/ ; 26830131//Japan Society for the Promotion of Science/ ; }, mesh = {Alleles ; Animals ; Base Sequence ; CRISPR-Cas Systems/genetics ; Genetic Engineering/*methods ; Injections ; Mice ; Mice, Knockout ; Zygote/metabolism ; }, abstract = {BACKGROUND: CRISPR/Cas9 enables the targeting of genes in zygotes; however, efficient approaches to create loxP-flanked (floxed) alleles remain elusive.

RESULTS: Here, we show that the electroporation of Cas9, two gRNAs, and long single-stranded DNA (lssDNA) into zygotes, termed CLICK (CRISPR with lssDNA inducing conditional knockout alleles), enables the quick generation of floxed alleles in mice and rats.

CONCLUSIONS: The high efficiency of CLICK provides homozygous knock-ins in oocytes carrying tissue-specific Cre, which allows the one-step generation of conditional knockouts in founder (F0) mice.}, } @article {pmid29720081, year = {2018}, author = {Lin, J and Wei, J and Adjeroh, D and Jiang, BH and Jiang, Y}, title = {SSAW: A new sequence similarity analysis method based on the stationary discrete wavelet transform.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {165}, pmid = {29720081}, issn = {1471-2105}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; 61472082//Chinese National Natural Science Foundation/International ; 2014J01220//Natural Science Foundation of Fujian Province of China/International ; IRTL1702//Scientific Research Innovation Team Construction Program of Fujian Normal University/International ; }, mesh = {*Algorithms ; Cluster Analysis ; Computational Biology/*methods ; Humans ; Sequence Analysis, DNA/*methods ; Sequence Analysis, Protein/*methods ; *Sequence Homology ; *Wavelet Analysis ; }, abstract = {BACKGROUND: Alignment-free sequence similarity analysis methods often lead to significant savings in computational time over alignment-based counterparts.

RESULTS: A new alignment-free sequence similarity analysis method, called SSAW is proposed. SSAW stands for Sequence Similarity Analysis using the Stationary Discrete Wavelet Transform (SDWT). It extracts k-mers from a sequence, then maps each k-mer to a complex number field. Then, the series of complex numbers formed are transformed into feature vectors using the stationary discrete wavelet transform. After these steps, the original sequence is turned into a feature vector with numeric values, which can then be used for clustering and/or classification.

CONCLUSIONS: Using two different types of applications, namely, clustering and classification, we compared SSAW against the the-state-of-the-art alignment free sequence analysis methods. SSAW demonstrates competitive or superior performance in terms of standard indicators, such as accuracy, F-score, precision, and recall. The running time was significantly better in most cases. These make SSAW a suitable method for sequence analysis, especially, given the rapidly increasing volumes of sequence data required by most modern applications.}, } @article {pmid29720079, year = {2018}, author = {Dufresnes, C and Lymberakis, P and Kornilios, P and Savary, R and Perrin, N and Stöck, M}, title = {Phylogeography of Aegean green toads (Bufo viridis subgroup): continental hybrid swarm vs. insular diversification with discovery of a new island endemic.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {67}, pmid = {29720079}, issn = {1471-2148}, support = {STO 493/2-2//Deutsche Forschungsgemeinschaft/International ; P2LAP3_171818//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; }, mesh = {Animals ; Base Sequence ; *Biodiversity ; Bufonidae/*classification ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Gene Flow ; Genetic Drift ; Genetics, Population ; Genome ; Greece ; *Islands ; Likelihood Functions ; Mitochondria/genetics ; Phylogeny ; *Phylogeography ; Reproductive Isolation ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Debated aspects in speciation research concern the amount of gene flow between incipient species under secondary contact and the modes by which post-zygotic isolation accumulates. Secondary contact zones of allopatric lineages, involving varying levels of divergence, provide natural settings for comparative studies, for which the Aegean (Eastern Mediterranean) geography offers unique scenarios. In Palearctic green toads (Bufo viridis subgroup or Bufotes), Plio-Pleistocene (~ 2.6 Mya) diverged species show a sharp transition without contemporary gene flow, while younger lineages, diverged in the Lower-Pleistocene (~ 1.9 Mya), admix over tens of kilometers. Here, we conducted a fine-scale multilocus phylogeographic analysis of continental and insular green toads from the Aegean, where a third pair of taxa, involving Mid-Pleistocene diverged (~ 1.5 Mya) mitochondrial lineages, earlier tentatively named viridis and variabilis, (co-)occurs.

RESULTS: We discovered a new lineage, endemic to Naxos (Central Cyclades), while coastal islands and Crete feature weak genetic differentiation from the continent. In continental Greece, both lineages, viridis and variabilis, form a hybrid swarm, involving massive mitochondrial and nuclear admixture over hundreds of kilometers, without obvious selection against hybrids.

CONCLUSIONS: The genetic signatures of insular Aegean toads appear governed by bathymetry and Quaternary sea level changes, resulting in long-term isolation (Central Cyclades: Naxos) and recent land-bridges (coastal islands). Conversely, Crete has been isolated since the end of the Messinian salinity crisis (5.3 My) and Cretan populations thus likely result from human-mediated colonization, at least since Antiquity, from Peloponnese and Anatolia. Comparisons of green toad hybrid zones support the idea that post-zygotic hybrid incompatibilities accumulate gradually over the genome. In this radiation, only one million years of divergence separate a scenario of complete reproductive isolation, from a secondary contact resulting in near panmixia.}, } @article {pmid29719167, year = {2018}, author = {Henry, IM and Akagi, T and Tao, R and Comai, L}, title = {One Hundred Ways to Invent the Sexes: Theoretical and Observed Paths to Dioecy in Plants.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {553-575}, doi = {10.1146/annurev-arplant-042817-040615}, pmid = {29719167}, issn = {1545-2123}, abstract = {Dioecy, the presence of male and female flowers on separate individuals, is both widespread and uncommon within flowering plants, with only a few percent of dioecious species spread across most major phylogenetic taxa. It is therefore safe to assume that dioecy evolved independently in these different groups, which allows us to ask questions regarding the molecular and developmental mechanisms underlying these independent transitions to dioecy. We start this review by examining the problem from the standpoint of a genetic engineer trying to develop dioecy, discuss various potential solutions, and compare them to models proposed in the past and based on genetic and evolutionary considerations. Next, we present recent information regarding candidate sex determinants in three species, acquired using newly established genomic approaches. Although such specific information is still scarce, it is slowly becoming apparent that various genes or pathways can be altered to evolve dioecy.}, } @article {pmid29719166, year = {2018}, author = {McElwain, JC}, title = {Paleobotany and Global Change: Important Lessons for Species to Biomes from Vegetation Responses to Past Global Change.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {761-787}, doi = {10.1146/annurev-arplant-042817-040405}, pmid = {29719166}, issn = {1545-2123}, abstract = {Human carbon use during the next century will lead to atmospheric carbon dioxide concentrations (pCO2) that have been unprecedented for the past 50-100+ million years according to fossil plant-based CO2 estimates. The paleobotanical record of plants offers key insights into vegetation responses to past global change, including suitable analogs for Earth's climatic future. Past global warming events have resulted in transient poleward migration at rates that are equivalent to the lowest climate velocities required for current taxa to keep pace with climate change. Paleobiome reconstructions suggest that the current tundra biome is the biome most threatened by global warming. The common occurrence of paleoforests at high polar latitudes when pCO2 was above 500 ppm suggests that the advance of woody shrub and tree taxa into tundra environments may be inevitable. Fossil pollen studies demonstrate the resilience of wet tropical forests to global change up to 700 ppm CO2, contrary to modeled predictions of the future. The paleobotanical record also demonstrates a high capacity for functional trait evolution as an additional strategy to migration and maintenance of a species' climate envelope in response to global change.}, } @article {pmid29719165, year = {2018}, author = {Liang, X and Zhou, JM}, title = {Receptor-Like Cytoplasmic Kinases: Central Players in Plant Receptor Kinase-Mediated Signaling.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {267-299}, doi = {10.1146/annurev-arplant-042817-040540}, pmid = {29719165}, issn = {1545-2123}, abstract = {Receptor kinases (RKs) are of paramount importance in transmembrane signaling that governs plant reproduction, growth, development, and adaptation to diverse environmental conditions. Receptor-like cytoplasmic kinases (RLCKs), which lack extracellular ligand-binding domains, have emerged as a major class of signaling proteins that regulate plant cellular activities in response to biotic/abiotic stresses and endogenous extracellular signaling molecules. By associating with immune RKs, RLCKs regulate multiple downstream signaling nodes to orchestrate a complex array of defense responses against microbial pathogens. RLCKs also associate with RKs that perceive brassinosteroids and signaling peptides to coordinate growth, pollen tube guidance, embryonic and stomatal patterning, floral organ abscission, and abiotic stress responses. The activity and stability of RLCKs are dynamically regulated not only by RKs but also by other RLCK-associated proteins. Analyses of RLCK-associated components and substrates have suggested phosphorylation relays as a major mechanism underlying RK-mediated signaling.}, } @article {pmid29719164, year = {2018}, author = {Walia, A and Waadt, R and Jones, AM}, title = {Genetically Encoded Biosensors in Plants: Pathways to Discovery.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {497-524}, doi = {10.1146/annurev-arplant-042817-040104}, pmid = {29719164}, issn = {1545-2123}, abstract = {Genetically encoded biosensors that directly interact with a molecule of interest were first introduced more than 20 years ago with fusion proteins that served as fluorescent indicators for calcium ions. Since then, the technology has matured into a diverse array of biosensors that have been deployed to improve our spatiotemporal understanding of molecules whose dynamics have profound influence on plant physiology and development. In this review, we address several types of biosensors with a focus on genetically encoded calcium indicators, which are now the most diverse and advanced group of biosensors. We then consider the discoveries in plant biology made by using biosensors for calcium, pH, reactive oxygen species, redox conditions, primary metabolites, phytohormones, and nutrients. These discoveries were dependent on the engineering, characterization, and optimization required to develop a successful biosensor; they were also dependent on the methodological developments required to express, detect, and analyze the readout of such biosensors.}, } @article {pmid29718509, year = {2018}, author = {Dong, Y and Liu, J and Li, PW and Li, CQ and Lü, TF and Yang, X and Wang, YZ}, title = {Evolution of Darwin's Peloric Gloxinia (Sinningia speciosa) Is Caused by a Null Mutation in a Pleiotropic TCP Gene.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1901-1915}, pmid = {29718509}, issn = {1537-1719}, abstract = {Unlike most crops, which were domesticated through long periods of selection by ancient humans, horticultural plants were primarily domesticated through intentional selection over short time periods. The molecular mechanisms underlying the origin and spread of novel traits in the domestication process have remained largely unexplored in horticultural plants. Gloxinia (Sinningia speciosa), whose attractive peloric flowers influenced the thoughts of Darwin, have been cultivated since the early 19th century, but its origin and genetic basis are currently unknown. By employing multiple experimental approaches including genetic analysis, genotype-phenotype associations, gene expression analysis, and functional interrogations, we showed that a single gene encoding a TCP protein, SsCYC, controls both floral orientation and zygomorphy in gloxinia. We revealed that a causal mutation responsible for the development of peloric gloxinia lies in a 10-bp deletion in the coding sequence of SsCYC. By combining genetic inference and literature searches, we have traced the putative ancestor and reconstructed the domestication path of the peloric gloxinia, in which a 10-bp deletion in SsCYC under selection triggered its evolution from the wild progenitor. The results presented here suggest that a simple genetic change in a pleiotropic gene can promote the elaboration of floral organs under intensive selection pressure.}, } @article {pmid29718454, year = {2018}, author = {Niida, A and Iwasaki, WM and Innan, H}, title = {Neutral Theory in Cancer Cell Population Genetics.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1316-1321}, doi = {10.1093/molbev/msy091}, pmid = {29718454}, issn = {1537-1719}, abstract = {Kimura's neutral theory provides the whole theoretical basis of the behavior of mutations in a Wright-Fisher population. We here discuss how it can be applied to a cancer cell population, in which there is an increasing interest in genetic variation within a tumor. We explain a couple of fundamental differences between cancer cell populations and asexual organismal populations. Once these differences are taken into account, a number of powerful theoretical tools developed for a Wright-Fisher population could be readily contribute to our deeper understanding of the evolutionary dynamics of cancer cell population.}, } @article {pmid29718409, year = {2018}, author = {Leitner, T}, title = {The Puzzle of HIV Neutral and Selective Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1355-1358}, doi = {10.1093/molbev/msy089}, pmid = {29718409}, issn = {1537-1719}, support = {R01 AI087520/AI/NIAID NIH HHS/United States ; }, abstract = {HIV is one of the fastest evolving organisms known. It evolves about 1 million times faster than its host, humans. Because HIV establishes chronic infections, with continuous evolution, its divergence within a single infected human surpasses the divergence of the entire humanoid history. Yet, it is still the same virus, infecting the same cell types and using the same replication machinery year after year. Hence, one would think that most mutations that HIV accumulates are neutral. But the picture is more complicated than that. HIV evolution is also a clear example of strong positive selection, that is, mutants have a survival advantage. How do these facts come together?}, } @article {pmid29718380, year = {2018}, author = {Ye, D and Zaidi, AA and Tomaszkiewicz, M and Anthony, K and Liebowitz, C and DeGiorgio, M and Shriver, MD and Makova, KD}, title = {High Levels of Copy Number Variation of Ampliconic Genes across Major Human Y Haplogroups.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1333-1350}, pmid = {29718380}, issn = {1759-6653}, mesh = {*Body Height ; *Chromosomes, Human, Y ; *DNA Copy Number Variations ; Evolution, Molecular ; *Gene Amplification ; Genome, Human ; Haplotypes ; Humans ; Male ; *Masculinity ; Multigene Family ; Phenotype ; }, abstract = {Because of its highly repetitive nature, the human male-specific Y chromosome remains understudied. It is important to investigate variation on the Y chromosome to understand its evolution and contribution to phenotypic variation, including infertility. Approximately 20% of the human Y chromosome consists of ampliconic regions which include nine multi-copy gene families. These gene families are expressed exclusively in testes and usually implicated in spermatogenesis. Here, to gain a better understanding of the role of the Y chromosome in human evolution and in determining sexually dimorphic traits, we studied ampliconic gene copy number variation in 100 males representing ten major Y haplogroups world-wide. Copy number was estimated with droplet digital PCR. In contrast to low nucleotide diversity observed on the Y in previous studies, here we show that ampliconic gene copy number diversity is very high. A total of 98 copy-number-based haplotypes were observed among 100 individuals, and haplotypes were sometimes shared by males from very different haplogroups, suggesting homoplasies. The resulting haplotypes did not cluster according to major Y haplogroups. Overall, only two gene families (RBMY and TSPY) showed significant differences in copy number among major Y haplogroups, and the haplogroup of a male could not be predicted based on his ampliconic gene copy numbers. Finally, we did not find significant correlations either between copy number variation and individual's height, or between the former and facial masculinity/femininity. Our results suggest rapid evolution of ampliconic gene copy numbers on the human Y, and we discuss its causes.}, } @article {pmid29718229, year = {2018}, author = {Potekhin, A and Schweikert, M and Nekrasova, I and Vitali, V and Schwarzer, S and Anikina, A and Kaltz, O and Petroni, G and Schrallhammer, M}, title = {Complex life cycle, broad host range and adaptation strategy of the intranuclear Paramecium symbiont Preeria caryophila comb. nov.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy076}, pmid = {29718229}, issn = {1574-6941}, abstract = {Holospora and related bacteria are a group of obligate Paramecium symbionts. Characteristic features are their infectivity, the presence of two distinct morphotypes, and usually a strict specialization for a single Paramecium species as host and for a nuclear compartment (either somatic or generative nucleus) for reproduction. Holospora caryophila steps out of line, naturally occurring in Paramecium biaurelia and Paramecium caudatum. This study addresses the phylogenetic relationship among H. caryophila and other Holospora species based on 16S rRNA gene sequence comparison analyzing the type strain and seven new macronuclear symbionts. Key aspects of Holospora physiology such as infectivity, symbiosis establishment and host range were determined by comprehensive infection assays. Detailed morphological investigations and sequence-based phylogeny confirmed a high similarity between the type strain of H. caryophila and the novel strains. Surprisingly, they are only distantly related to other Holospora species suggesting that they belong to a new genus within the family Holosporaceae, here described as Preeria caryophila comb. nov. Adding to this phylogenetic distance, we also observed a much broader host range, comprising at least eleven Paramecium species. As these potential host species exhibit substantial differences in frequency of sexual processes, P. caryophila demonstrates which adaptations are crucial for macronuclear symbionts facing regular destruction of their habitat.}, } @article {pmid29718211, year = {2018}, author = {Kapust, N and Nelson-Sathi, S and Schönfeld, B and Hazkani-Covo, E and Bryant, D and Lockhart, PJ and Röttger, M and Xavier, JC and Martin, WF}, title = {Failure to Recover Major Events of Gene Flux in Real Biological Data Due to Method Misapplication.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1198-1209}, pmid = {29718211}, issn = {1759-6653}, mesh = {Archaea/genetics ; Chloroplast Proteins/genetics ; Computational Biology/*standards ; Eukaryota/genetics ; *Evolution, Molecular ; *Gene Transfer, Horizontal ; Genome, Plastid ; Genomics ; Models, Genetic ; *Phylogeny ; Plastids/*classification/*genetics ; Software ; Symbiosis/genetics ; Validation Studies as Topic ; }, abstract = {In prokaryotes, known mechanisms of lateral gene transfer (transformation, transduction, conjugation, and gene transfer agents) generate new combinations of genes among chromosomes during evolution. In eukaryotes, whose host lineage is descended from archaea, lateral gene transfer from organelles to the nucleus occurs at endosymbiotic events. Recent genome analyses studying gene distributions have uncovered evidence for sporadic, discontinuous events of gene transfer from bacteria to archaea during evolution. Other studies have used traditional models designed to investigate gene family size evolution (Count) to support claims that gene transfer to archaea was continuous during evolution, rather than involving occasional periodic mass gene influx events. Here, we show that the methodology used in analyses favoring continuous gene transfers to archaea was misapplied in other studies and does not recover known events of single simultaneous origin for many genes followed by differential loss in real data: plastid genomes. Using the same software and the same settings, we reanalyzed presence/absence pattern data for proteins encoded in plastid genomes and for eukaryotic protein families acquired from plastids. Contrary to expectations under a plastid origin model, we found that the methodology employed inferred that gene acquisitions occurred uniformly across the plant tree. Sometimes as many as nine different acquisitions by plastid DNA were inferred for the same protein family. That is, the methodology that recovered gradual and continuous lateral gene transfer among lineages for archaea obtains the same result for plastids, even though it is known that massive gains followed by gradual differential loss is the true evolutionary process that generated plastid gene distribution data. Our findings caution against the use of models designed to study gene family size evolution for investigating gene transfer processes, especially when transfers involving more than one gene per event are possible.}, } @article {pmid29718209, year = {2018}, author = {McGrath, C}, title = {Highlight: Big Surprises from the World's Smallest Fish.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1104-1105}, pmid = {29718209}, issn = {1759-6653}, mesh = {Animals ; Body Size/*genetics ; Cyprinidae/anatomy & histology/genetics ; Genes, Homeobox/*genetics ; Genome/*genetics ; }, } @article {pmid29718208, year = {2018}, author = {}, title = {The Novel Evolution of the Sperm Whale Genome.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1063}, doi = {10.1093/gbe/evy069}, pmid = {29718208}, issn = {1759-6653}, } @article {pmid29718207, year = {2018}, author = {}, title = {Determinants of the efficacy of natural selection on coding and noncoding variability in two passerine species.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1062}, doi = {10.1093/gbe/evy068}, pmid = {29718207}, issn = {1759-6653}, } @article {pmid29718191, year = {2018}, author = {Oh, M and Pruden, A and Chen, C and Heath, LS and Xia, K and Zhang, L}, title = {MetaCompare: a computational pipeline for prioritizing environmental resistome risk.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, pmid = {29718191}, issn = {1574-6941}, abstract = {The spread of antibiotic resistance is a growing public health concern. While numerous studies have highlighted the importance of environmental sources and pathways of the spread of antibiotic resistance, a systematic means of comparing and prioritizing risks represented by various environmental compartments is lacking. Here, we introduce MetaCompare, a publicly available tool for ranking 'resistome risk', which we define as the potential for antibiotic resistance genes (ARGs) to be associated with mobile genetic elements (MGEs) and mobilize to pathogens based on metagenomic data. A computational pipeline was developed in which each ARG is evaluated based on relative abundance, mobility, and presence within a pathogen. This is determined through the assembly of shotgun sequencing data and analysis of contigs containing ARGs to determine if they contain sequence similarity to MGEs or human pathogens. Based on the assembled metagenomes, samples are projected into a 3-dimensionalhazard space and assigned resistome risk scores. To validate, we tested previously published metagenomic data derived from distinct aquatic environments. Based on unsupervised machine learning, the test samples clustered in the hazard space in a manner consistent with their origin. The derived scores produced a well-resolved ascending resistome risk ranking of: wastewater treatment plant effluent, dairy lagoon, and hospital sewage.}, } @article {pmid29718181, year = {2018}, author = {Alves, M and Pereira, A and Vicente, C and Matos, P and Henriques, J and Lopes, H and Nascimento, F and Mota, M and Correia, A and Henriques, I}, title = {The role of bacteria in pine wilt disease: insights from microbiome analysis.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy077}, pmid = {29718181}, issn = {1574-6941}, abstract = {Pine Wilt Disease (PWD) has a significant impact on Eurasia pine forests. The microbiome of the nematode (the primary cause of the disease), its insect vector, and the host tree may be relevant for the disease mechanism. The aim of this study was to characterize these microbiomes, from three PWD-affected areas in Portugal, using Denaturing Gradient Gel Electrophoresis, 16S rRNA gene pyrosequencing, and a functional inference-based approach (PICRUSt). The bacterial community structure of the nematode was significantly different from the infected trees but closely related to the insect vector, supporting the hypothesis that the nematode microbiome might be in part inherited from the insect. Sampling location influenced mostly the tree microbiome (P < 0.05). Genes related both with plant growth promotion and phytopathogenicity were predicted for the tree microbiome. Xenobiotic degradation functions were predicted in the nematode and insect microbiomes. Phytotoxin biosynthesis was also predicted for the nematode microbiome, supporting the theory of a direct contribution of the microbiome to tree-wilting. This is the first study that simultaneously characterized the nematode, tree and insect-vector microbiomes from the same affected areas, and overall the results support the hypothesis that the PWD microbiome plays an important role in the disease's development.}, } @article {pmid29718180, year = {2018}, author = {Schmidt, R and Durling, MB and de Jager, V and Menezes, RC and Nordkvist, E and Svatoš, A and Dubey, M and Lauterbach, L and Dickschat, JS and Karlsson, M and Garbeva, P}, title = {Deciphering the genome and secondary metabolome of the plant pathogen Fusarium culmorum.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy078}, pmid = {29718180}, issn = {1574-6941}, abstract = {Fusarium culmorum is one of the most important fungal plant pathogens that causes diseases on a wide diversity of cereal and non-cereal crops. We report herein for the first time the genome sequence of F. culmorum strain PV and its associated secondary metabolome that plays a role in the interaction with other microorganisms and contributes to its pathogenicity on plants. The genome revealed the presence of two terpene synthases, trichodiene and longiborneol synthase, which generate an array of volatile terpenes. Furthermore, we identified two gene clusters, deoxynivalenol and zearalenone, which encode for the production of mycotoxins. Linking the production of mycotoxins with in vitro bioassays, we found high virulence of F. culmorum PV on maize, barley and wheat. By using ultra-performance liquid chromatography-mass spectrometry, we confirmed several compounds important for the behaviour and lifestyle of F. culmorum. This research sets the basis for future studies in microbe-plant interactions.}, } @article {pmid29718172, year = {2018}, author = {Schubert, T and Adrian, L and Sawers, RG and Diekert, G}, title = {Organohalide respiratory chains: composition, topology and key enzymes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy035}, pmid = {29718172}, issn = {1574-6941}, abstract = {The utilization of halogenated organic compounds as terminal electron acceptors separates the phylogenetically diverse organohalide-respiring bacteria from other respiratory anaerobes that predominantly use nitrate, fumarate, sulfate or oxidized metals. Organohalide respiration is unique in recruiting a cobamide-containing iron-sulfur protein, the extracellular membrane-bound reductive dehalogenase, as terminal reductase in the electron transfer chain. In recent years substantial contributions have been made to the understanding of how electron transfer paths couple mechanistically to chemiosmosis in the organohalide-respiring bacteria. The structural analysis of a respiratory and a non-respiratory reductive dehalogenase revealed the intramolecular electron transfer via two cubane iron-sulfur clusters to the cobamide at the active site. Based on whether quinones are involved, two types of intermolecular electron transfer chains have been identified, which differ in their composition and mode of proton translocation. Indeed, various respiratory chain architectures have been unraveled and evidence for different putative coupling mechanisms presented. The identification of a multienzyme respiratory complex that combines uptake hydrogenase, a complex iron-sulfur molybdoenzyme and a reductive dehalogenase in Dehalococcoides mccartyi strain CBDB1 has raised new questions regarding the mode of energy conservation in these enigmatic microbes. In this mini-review, we highlight these findings and provide an outlook on potential future developments.}, } @article {pmid29717973, year = {2018}, author = {Niu, L and Hu, S and Lu, S and Lai, XH and Yang, J and Jin, D and Rao, L and Lu, G and Xu, J}, title = {Isolation and characterization of Streptococcus respiraculi sp. nov. from Marmota himalayana (Himalayan marmot) respiratory tract.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2082-2087}, doi = {10.1099/ijsem.0.002806}, pmid = {29717973}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Genes, Bacterial ; Marmota/*microbiology ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Respiratory System/*microbiology ; Sequence Analysis, DNA ; Streptococcus/*classification/genetics/isolation & purification ; }, abstract = {Two bacterial strains were individually isolated from Marmota himalayana respiratory tracts; the animals were from the Tibet-Qinghai Plateau, PR China. The isolates were Gram-stain-positive, catalase-negative, coccus-shaped, chain-forming organisms. Analysis of 16S rRNA gene sequences indicated that the type strain HTS25T shared 98.0, 97.4, 97.2 and 97.1 % similarity with Streptococcus cuniculi, Streptococcus acidominimus, Streptococcus marmotae and Streptococcus himalayensis respectively. Sequence analysis of the sodA and rpoB genes indicated that HTS25T was closely related to S. marmotae (similarities of 94.7 and 91.4 % respectively). Analysis of groEL sequences showed interspecies similarity of 84.8 % between HTS25T and S. himalayensis. A whole-genome phylogenetic tree reconstructed from 81 core genes from the genomes of 17 members of the genus Streptococcus was used to validate that HTS25T forms a distinct subline from other recognized species of the genus Streptococcus. DNA-DNA hybridization of HTS25T showed a maximum estimated DNA reassociation value of 32.1 % to Streptococcus cuniculi CCUG 65085T. On the basis of the results of phenotypic and phylogenetic analyses, we propose that the two isolates be classified as representing a novel species of the genus Streptococcus, named Streptococcus respiraculi sp. nov. The type strain is HTS25T (=DSM 101998T=CGMCC 1.15531T). The genome of Streptococcus respiraculi sp. nov. strain HTS25T (2 067 971 bp) contains 2001 genes with an average DNA G+C content of 42.7 mol%.}, } @article {pmid29717971, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations and new taxonomic opinions have appeared in volume 68, part 2, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1409-1410}, doi = {10.1099/ijsem.0.002630}, pmid = {29717971}, issn = {1466-5034}, } @article {pmid29717968, year = {2018}, author = {Feng, T and Kim, KH and Chun, BH and Jeon, CO}, title = {Amylibacter lutimaris sp. nov., isolated from sea-tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2088-2092}, doi = {10.1099/ijsem.0.002805}, pmid = {29717968}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic bacterial strain, designated strain m18T, was isolated from a sea-tidal flat in South Korea. Cells were non-motile short rods showing oxidase and catalase activities. Growth of m18T was observed at 10-40 °C (optimum, 30 °C), pH 5.5-10.0 (optimum, pH 7.0) and 0.5-7.0 % (w/v) NaCl (optimum, 3.0 %). The major respiratory quinone was ubiquinone-10 and the major fatty acids of were summed feature 8 (comprising C18 : 1ω7c/C18 : 1ω6c) and C16 : 0. The G+C content of the genomic DNA was 56.7 mol%. Phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, an unidentified phospholipid, an unidentified aminolipid and four unidentified lipids were detected in m18T. The results of phylogenetic analysis based on 16S rRNA gene sequences indicated that m18T formed a tight phyletic lineage with the members of the genus Amylibacter. Strain m18T was most closely related to Amylibactercionae H-12T, Amylibacter ulvae 6Alg 255T and Amylibacter marinus 2-3T with 98.9, 96.1 and 95.5 % 16S rRNA gene sequence similarities, respectively. The DNA-DNA hybridization value between m18T and the type strain of A. cionae was 43.6±3.4 %. On the basis of phenotypic, chemotaxonomic and molecular properties, m18T represents a novel species of the genus Amylibacter, for which the name Amylibacterlutimaris sp. nov. is proposed. The type strain is m18T (KACC 19229T=JCM 32051T).}, } @article {pmid29717257, year = {2018}, author = {}, title = {Real-world illness requires medical multitasking.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {5-6}, doi = {10.1038/d41586-018-05028-w}, pmid = {29717257}, issn = {1476-4687}, mesh = {Humans ; *Neuropsychological Tests ; }, } @article {pmid29717256, year = {2018}, author = {Dolgin, E}, title = {Scientists downsize bold plan to make human genome from scratch.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {16-17}, doi = {10.1038/d41586-018-05043-x}, pmid = {29717256}, issn = {1476-4687}, mesh = {Biotechnology/economics/*methods ; Cell Line ; Codon/genetics ; Escherichia coli/genetics/virology ; *Gene Editing ; Genetic Code/genetics ; Genome, Human/*genetics ; Genomics/economics/*methods ; Humans ; Investments ; Pilot Projects ; Public-Private Sector Partnerships/economics ; Virus Diseases/economics/*genetics/immunology/*prevention & control ; }, } @article {pmid29717254, year = {2018}, author = {Darnall, B}, title = {To treat pain, study people in all their complexity.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {7}, doi = {10.1038/d41586-018-04994-5}, pmid = {29717254}, issn = {1476-4687}, mesh = {Humans ; *Pain ; *Pain Management ; }, } @article {pmid29717253, year = {2018}, author = {Tollefson, J}, title = {Brazil's lawmakers renew push to weaken environmental rules.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {17}, doi = {10.1038/d41586-018-05022-2}, pmid = {29717253}, issn = {1476-4687}, mesh = {Brazil ; Crop Production/*legislation & jurisprudence ; Environmental Policy/*legislation & jurisprudence ; *Federal Government ; Politics ; *Rainforest ; Saccharum/growth & development ; }, } @article {pmid29717252, year = {2018}, author = {}, title = {Unconventional lifestyle found in island bird.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {9}, doi = {10.1038/d41586-018-05009-z}, pmid = {29717252}, issn = {1476-4687}, } @article {pmid29717250, year = {2018}, author = {Baneyx, F}, title = {Protein and gel combined to make hyperexpandable crystals.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {38-39}, doi = {10.1038/d41586-018-04956-x}, pmid = {29717250}, issn = {1476-4687}, mesh = {*Crystallization ; *Proteins ; }, } @article {pmid29717249, year = {2018}, author = {Padian, K}, title = {Evolutionary insights from an ancient bird.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {36-37}, doi = {10.1038/d41586-018-04780-3}, pmid = {29717249}, issn = {1476-4687}, mesh = {Animals ; *Biological Evolution ; Birds ; Fossils ; *Paleontology ; Phylogeny ; }, } @article {pmid29717248, year = {2018}, author = {Deming, D}, title = {Helium discovered in the tail of an exoplanet.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {35-36}, doi = {10.1038/d41586-018-04969-6}, pmid = {29717248}, issn = {1476-4687}, mesh = {Astronomical Phenomena ; Astronomy ; Exobiology ; *Helium ; *Planets ; }, } @article {pmid29717246, year = {2018}, author = {}, title = {Measuring the Milky Way's mind-boggling mass.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {9}, doi = {10.1038/d41586-018-04970-z}, pmid = {29717246}, issn = {1476-4687}, } @article {pmid29717245, year = {2018}, author = {}, title = {Souped-up T cells home in on cancer.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {8}, doi = {10.1038/d41586-018-04974-9}, pmid = {29717245}, issn = {1476-4687}, } @article {pmid29717244, year = {2018}, author = {Castelvecchi, D}, title = {Physicists in Earth's remotest corners race to reproduce 'cosmic dawn' signal.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {15-16}, doi = {10.1038/d41586-018-04966-9}, pmid = {29717244}, issn = {1476-4687}, } @article {pmid29717243, year = {2018}, author = {}, title = {Abandoned fort holds clues to mass slaughter.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {8-9}, doi = {10.1038/d41586-018-04973-w}, pmid = {29717243}, issn = {1476-4687}, } @article {pmid29717242, year = {2018}, author = {Maxmen, A}, title = {Giving at-risk children pre-emptive antibiotics reduces deaths.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {14-15}, doi = {10.1038/d41586-018-04962-z}, pmid = {29717242}, issn = {1476-4687}, mesh = {*Anti-Bacterial Agents ; Child ; *Child Mortality ; Humans ; }, } @article {pmid29717241, year = {2018}, author = {Castelvecchi, D}, title = {Billion-star map of Milky Way set to transform astronomy.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {18}, doi = {10.1038/d41586-018-04979-4}, pmid = {29717241}, issn = {1476-4687}, } @article {pmid29717240, year = {2018}, author = {}, title = {Early stick insect was a master of disguise.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {9}, doi = {10.1038/d41586-018-04971-y}, pmid = {29717240}, issn = {1476-4687}, } @article {pmid29717239, year = {2018}, author = {Witze, A}, title = {Mars quakes set to reveal tantalizing clues to planet's early years.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {13-14}, doi = {10.1038/d41586-018-04964-x}, pmid = {29717239}, issn = {1476-4687}, } @article {pmid29717238, year = {2018}, author = {}, title = {Arctic ice carries heavy freight of plastic.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {8}, doi = {10.1038/d41586-018-04967-8}, pmid = {29717238}, issn = {1476-4687}, } @article {pmid29717237, year = {2018}, author = {}, title = {Kids beat elite runners in fitness tests.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {8}, doi = {10.1038/d41586-018-04961-0}, pmid = {29717237}, issn = {1476-4687}, } @article {pmid29717236, year = {2018}, author = {}, title = {More whiplash weather in store for California.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {9}, doi = {10.1038/d41586-018-04960-1}, pmid = {29717236}, issn = {1476-4687}, } @article {pmid29717235, year = {2018}, author = {}, title = {Fibre aids fight against nasty gut infection.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {9}, doi = {10.1038/d41586-018-04957-w}, pmid = {29717235}, issn = {1476-4687}, } @article {pmid29717101, year = {2018}, author = {Perkins, S}, title = {Inner Workings: A new crop of landers and rovers seeks to answer key questions about Venus-and, by extension, Earth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4525-4527}, pmid = {29717101}, issn = {1091-6490}, } @article {pmid29717100, year = {2018}, author = {Carey, J}, title = {Science and Culture: Animal cognition research offers outreach opportunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4522-4524}, pmid = {29717100}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; Cognition ; Conservation of Natural Resources/methods ; Education/*methods ; Elephants/*psychology ; Humans ; Intelligence ; Students/psychology ; }, } @article {pmid29717043, year = {2018}, author = {Hsu, CP and Ramakrishna, SN and Zanini, M and Spencer, ND and Isa, L}, title = {Roughness-dependent tribology effects on discontinuous shear thickening.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5117-5122}, pmid = {29717043}, issn = {1091-6490}, abstract = {Surface roughness affects many properties of colloids, from depletion and capillary interactions to their dispersibility and use as emulsion stabilizers. It also impacts particle-particle frictional contacts, which have recently emerged as being responsible for the discontinuous shear thickening (DST) of dense suspensions. Tribological properties of these contacts have been rarely experimentally accessed, especially for nonspherical particles. Here, we systematically tackle the effect of nanoscale surface roughness by producing a library of all-silica, raspberry-like colloids and linking their rheology to their tribology. Rougher surfaces lead to a significant anticipation of DST onset, in terms of both shear rate and solid loading. Strikingly, they also eliminate continuous thickening. DST is here due to the interlocking of asperities, which we have identified as "stick-slip" frictional contacts by measuring the sliding of the same particles via lateral force microscopy (LFM). Direct measurements of particle-particle friction therefore highlight the value of an engineering-tribology approach to tuning the thickening of suspensions.}, } @article {pmid29717042, year = {2018}, author = {Maiorano, A and Parisi, G}, title = {Support for the value 5/2 for the spin glass lower critical dimension at zero magnetic field.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5129-5134}, pmid = {29717042}, issn = {1091-6490}, abstract = {We study numerically various properties of the free energy barriers in the Edwards-Anderson model of spin glasses in the low-temperature region in both three and four spatial dimensions. In particular, we investigated the dependence of height of free energy barriers on system size and on the distance between the initial and final states (i.e., the overlap distance). A related quantity is the distribution of large local fluctuations of the overlap in large 3D samples at equilibrium. Our results for both quantities (barriers and large deviations) are in agreement with the prediction obtained in the framework of mean-field theory. In addition, our result supports [Formula: see text] as the lower critical dimension of the model.}, } @article {pmid29717041, year = {2018}, author = {Samanta, D and Gemen, J and Chu, Z and Diskin-Posner, Y and Shimon, LJW and Klajn, R}, title = {Reversible photoswitching of encapsulated azobenzenes in water.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9379-9384}, pmid = {29717041}, issn = {1091-6490}, abstract = {Efficient molecular switching in confined spaces is critical for the successful development of artificial molecular machines. However, molecular switching events often entail large structural changes and therefore require conformational freedom, which is typically limited under confinement conditions. Here, we investigated the behavior of azobenzene-the key building block of light-controlled molecular machines-in a confined environment that is flexible and can adapt its shape to that of the bound guest. To this end, we encapsulated several structurally diverse azobenzenes within the cavity of a flexible, water-soluble coordination cage, and investigated their light-responsive behavior. Using UV/Vis absorption spectroscopy and a combination of NMR methods, we showed that each of the encapsulated azobenzenes exhibited distinct switching properties. An azobenzene forming a 1:1 host-guest inclusion complex could be efficiently photoisomerized in a reversible fashion. In contrast, successful switching in inclusion complexes incorporating two azobenzene guests was dependent on the availability of free cages in the system, and it involved reversible trafficking of azobenzene between the cages. In the absence of extra cages, photoswitching was either suppressed or it involved expulsion of azobenzene from the cage and consequently its precipitation from the solution. This finding was utilized to develop an information storage medium in which messages could be written and erased in a reversible fashion using light.}, } @article {pmid29717040, year = {2018}, author = {van Velzen, R and Holmer, R and Bu, F and Rutten, L and van Zeijl, A and Liu, W and Santuari, L and Cao, Q and Sharma, T and Shen, D and Roswanjaya, Y and Wardhani, TAK and Kalhor, MS and Jansen, J and van den Hoogen, J and Güngör, B and Hartog, M and Hontelez, J and Verver, J and Yang, WC and Schijlen, E and Repin, R and Schilthuizen, M and Schranz, ME and Heidstra, R and Miyata, K and Fedorova, E and Kohlen, W and Bisseling, T and Smit, S and Geurts, R}, title = {Comparative genomics of the nonlegume Parasponia reveals insights into evolution of nitrogen-fixing rhizobium symbioses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4700-E4709}, pmid = {29717040}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; *Biological Evolution ; Fabaceae/*genetics/microbiology ; Genomics/*methods ; Nitrogen/metabolism ; *Nitrogen Fixation ; Phenotype ; Phylogeny ; Plant Proteins/*genetics ; Plant Root Nodulation/*genetics ; Rhizobium/*physiology ; Root Nodules, Plant ; Sequence Homology ; *Symbiosis ; }, abstract = {Nodules harboring nitrogen-fixing rhizobia are a well-known trait of legumes, but nodules also occur in other plant lineages, with rhizobia or the actinomycete Frankia as microsymbiont. It is generally assumed that nodulation evolved independently multiple times. However, molecular-genetic support for this hypothesis is lacking, as the genetic changes underlying nodule evolution remain elusive. We conducted genetic and comparative genomics studies by using Parasponia species (Cannabaceae), the only nonlegumes that can establish nitrogen-fixing nodules with rhizobium. Intergeneric crosses between Parasponia andersonii and its nonnodulating relative Trema tomentosa demonstrated that nodule organogenesis, but not intracellular infection, is a dominant genetic trait. Comparative transcriptomics of P. andersonii and the legume Medicago truncatula revealed utilization of at least 290 orthologous symbiosis genes in nodules. Among these are key genes that, in legumes, are essential for nodulation, including NODULE INCEPTION (NIN) and RHIZOBIUM-DIRECTED POLAR GROWTH (RPG). Comparative analysis of genomes from three Parasponia species and related nonnodulating plant species show evidence of parallel loss in nonnodulating species of putative orthologs of NIN, RPG, and NOD FACTOR PERCEPTION Parallel loss of these symbiosis genes indicates that these nonnodulating lineages lost the potential to nodulate. Taken together, our results challenge the view that nodulation evolved in parallel and raises the possibility that nodulation originated ∼100 Mya in a common ancestor of all nodulating plant species, but was subsequently lost in many descendant lineages. This will have profound implications for translational approaches aimed at engineering nitrogen-fixing nodules in crop plants.}, } @article {pmid29717039, year = {2018}, author = {Lu, X and Vitousek, PM and Mao, Q and Gilliam, FS and Luo, Y and Zhou, G and Zou, X and Bai, E and Scanlon, TM and Hou, E and Mo, J}, title = {Plant acclimation to long-term high nitrogen deposition in an N-rich tropical forest.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5187-5192}, pmid = {29717039}, issn = {1091-6490}, mesh = {*Acclimatization ; *Ecosystem ; *Forests ; Nitrogen/chemistry/*metabolism ; *Plant Physiological Phenomena ; Plants/*metabolism ; Soil ; }, abstract = {Anthropogenic nitrogen (N) deposition has accelerated terrestrial N cycling at regional and global scales, causing nutrient imbalance in many natural and seminatural ecosystems. How added N affects ecosystems where N is already abundant, and how plants acclimate to chronic N deposition in such circumstances, remains poorly understood. Here, we conducted an experiment employing a decade of N additions to examine ecosystem responses and plant acclimation to added N in an N-rich tropical forest. We found that N additions accelerated soil acidification and reduced biologically available cations (especially Ca and Mg) in soils, but plants maintained foliar nutrient supply at least in part by increasing transpiration while decreasing soil water leaching below the rooting zone. We suggest a hypothesis that cation-deficient plants can adjust to elevated N deposition by increasing transpiration and thereby maintaining nutrient balance. This result suggests that long-term elevated N deposition can alter hydrological cycling in N-rich forest ecosystems.}, } @article {pmid29717038, year = {2018}, author = {Wang, W and Yang, J and Zhang, J and Wang, Y and Hwang, SH and Qi, W and Wan, D and Kim, D and Sun, J and Sanidad, KZ and Yang, H and Park, Y and Liu, JY and Zhao, X and Zheng, X and Liu, Z and Hammock, BD and Zhang, G}, title = {Lipidomic profiling reveals soluble epoxide hydrolase as a therapeutic target of obesity-induced colonic inflammation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5283-5288}, pmid = {29717038}, issn = {1091-6490}, support = {P42 ES004699/ES/NIEHS NIH HHS/United States ; R01 ES002710/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Colitis/*etiology/metabolism/pathology ; Diet, High-Fat/*adverse effects ; Epoxide Hydrolases/*physiology ; Inflammation/*etiology/metabolism/pathology ; Lipids/*analysis ; Male ; Metabolomics/*methods ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Obesity/*complications ; Signal Transduction ; }, abstract = {Obesity is associated with enhanced colonic inflammation, which is a major risk factor for colorectal cancer. Considering the obesity epidemic in Western countries, it is important to identify novel therapeutic targets for obesity-induced colonic inflammation, to develop targeted strategies for prevention. Eicosanoids are endogenous lipid signaling molecules involved in regulating inflammation and immune responses. Using an LC-MS/MS-based lipidomics approach, we find that obesity-induced colonic inflammation is associated with increased expression of soluble epoxide hydrolase (sEH) and its eicosanoid metabolites, termed fatty acid diols, in colon tissue. Furthermore, we find that pharmacological inhibition or genetic ablation of sEH reduces colonic concentrations of fatty acid diols, attenuates obesity-induced colonic inflammation, and decreases obesity-induced activation of Wnt signaling in mice. Together, these results support that sEH could be a novel therapeutic target for obesity-induced colonic inflammation and associated diseases.}, } @article {pmid29716949, year = {2018}, author = {Sweeney, HL and Holzbaur, ELF}, title = {Motor Proteins.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a021931}, pmid = {29716949}, issn = {1943-0264}, support = {R35 GM126950/GM/NIGMS NIH HHS/United States ; }, abstract = {SUMMARYMyosin motors power movements on actin filaments, whereas dynein and kinesin motors power movements on microtubules. The mechanisms of these motor proteins differ, but, in all cases, ATP hydrolysis and subsequent release of the hydrolysis products drives a cycle of interactions with the track (either an actin filament or a microtubule), resulting in force generation and directed movement.}, } @article {pmid29716745, year = {2018}, author = {Marigorta, UM and Rodríguez, JA and Gibson, G and Navarro, A}, title = {Replicability and Prediction: Lessons and Challenges from GWAS.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {7}, pages = {504-517}, pmid = {29716745}, issn = {0168-9525}, support = {P01 GM099568/GM/NIGMS NIH HHS/United States ; R01 DK087694/DK/NIDDK NIH HHS/United States ; }, abstract = {Since the publication of the Wellcome Trust Case Control Consortium (WTCCC) landmark study a decade ago, genome-wide association studies (GWAS) have led to the discovery of thousands of risk variants involved in disease etiology. This success story has two angles that are often overlooked. First, GWAS findings are highly replicable. This is an unprecedented phenomenon in complex trait genetics, and indeed in many areas of science, which in past decades have been plagued by false positives. At a time of increasing concerns about the lack of reproducibility, we examine the biological and methodological reasons that account for the replicability of GWAS and identify the challenges ahead. In contrast to the exemplary success of disease gene discovery, at present GWAS findings are not useful for predicting phenotypes. We close with an overview of the prospects for individualized prediction of disease risk and its foreseeable impact in clinical practice.}, } @article {pmid29716744, year = {2018}, author = {Ponnikas, S and Sigeman, H and Abbott, JK and Hansson, B}, title = {Why Do Sex Chromosomes Stop Recombining?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {7}, pages = {492-503}, doi = {10.1016/j.tig.2018.04.001}, pmid = {29716744}, issn = {0168-9525}, abstract = {It is commonly assumed that sex chromosomes evolve recombination suppression because selection favours linkage between sex-determining and sexually antagonistic genes. However, although the role of sexual antagonism during sex chromosome evolution has attained strong support from theory, experimental and observational evidence is rare or equivocal. Here, we highlight alternative, often neglected, hypotheses for recombination suppression on sex chromosomes, which invoke meiotic drive, heterozygote advantage, and genetic drift, respectively. We contrast the hypotheses, the situations when they are likely to be of importance, and outline why it is surprisingly difficult to test them. Lastly, we discuss future research directions (including modelling, population genomics, comparative approaches, and experiments) to disentangle the different hypotheses of sex chromosome evolution.}, } @article {pmid29716742, year = {2018}, author = {Brito-Morales, I and García Molinos, J and Schoeman, DS and Burrows, MT and Poloczanska, ES and Brown, CJ and Ferrier, S and Harwood, TD and Klein, CJ and McDonald-Madden, E and Moore, PJ and Pandolfi, JM and Watson, JEM and Wenger, AS and Richardson, AJ}, title = {Climate Velocity Can Inform Conservation in a Warming World.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {441-457}, doi = {10.1016/j.tree.2018.03.009}, pmid = {29716742}, issn = {1872-8383}, mesh = {*Biodiversity ; *Climate Change ; *Conservation of Natural Resources ; Global Warming ; Oceans and Seas ; }, abstract = {Climate change is shifting the ranges of species. Simple predictive metrics of range shifts such as climate velocity, that do not require extensive knowledge or data on individual species, could help to guide conservation. We review research on climate velocity, describing the theory underpinning the concept and its assumptions. We highlight how climate velocity has already been applied in conservation-related research, including climate residence time, climate refugia, endemism, historic and projected range shifts, exposure to climate change, and climate connectivity. Finally, we discuss ways to enhance the use of climate velocity in conservation through tailoring it to be more biologically meaningful, informing design of protected areas, conserving ocean biodiversity in 3D, and informing conservation actions.}, } @article {pmid29716741, year = {2018}, author = {Niven, JE and Bell, ATA}, title = {Lessons in Lateralisation from the Insects.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {7}, pages = {486-488}, doi = {10.1016/j.tree.2018.04.008}, pmid = {29716741}, issn = {1872-8383}, abstract = {The behavioural lateralisation of a species is thought to be influenced by social organisation. However, recent studies of insect species with different social structures suggest that traits showing both population-level and individual-level lateralisation can be found in single species. This has broad implications for our understanding of how lateralisation and handedness evolves.}, } @article {pmid29716659, year = {2018}, author = {Lekota, KE and Hassim, A and Rogers, P and Dekker, EH and Last, R and de Klerk-Lorist, L and van Heerden, H}, title = {The reporting of a Bacillus anthracis B-clade strain in South Africa after more than 20 years.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {264}, pmid = {29716659}, issn = {1756-0500}, support = {78909//National Research Foundation/ ; }, mesh = {Acinonyx ; Animals ; Anthrax/*diagnosis/microbiology/veterinary ; Bacillus anthracis/*genetics/isolation & purification ; Humans ; Polymorphism, Single Nucleotide ; South Africa ; Whole Genome Sequencing ; Zoonoses ; }, abstract = {OBJECTIVES: Anthrax is a disease with an age old history in Africa caused by the Gram-positive endospore forming soil bacterium Bacillus anthracis. Epizootics of wild ungulates occur annually in the enzootic region of Pafuri, Kruger National Park (KNP) in the Limpopo Province of South Africa. Rigorous routine surveillance and diagnostics in KNP, has not revealed these rare isolates since the 1990s, despite unabated annual outbreaks. In 2011 a cheetah was diagnosed as anthrax positive from a private game reserve in Limpopo Province and reported to State Veterinary Services for further investigation. Isolation, molecular diagnostics, whole genome sequencing and comparative genomics were carried out for B. anthracis KC2011.

RESULTS: Bacteriological and molecular diagnostics confirmed the isolate as B. anthracis. Subsequent typing and whole genome single nucleotide polymorphisms analysis indicated it clustered alongside B. anthracis SA A0091 in the B.Br.010 SNP branch. Unlike B. anthracis KrugerB strain, KC2011 strain has unique SNPs and represents a new branch in the B-clade. The isolation and genotypic characterisation of KC2011 demonstrates a gap in the reporting of anthrax outbreaks in the greater Limpopo province area. The identification of vulnerable and susceptible cheetah mortalities due to this strain has implications for conservation measures and disease control.}, } @article {pmid29716650, year = {2018}, author = {van de Guchte, M and Blottière, HM and Doré, J}, title = {Humans as holobionts: implications for prevention and therapy.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {81}, pmid = {29716650}, issn = {2049-2618}, mesh = {Bacteria/classification/*immunology ; Bacterial Physiological Phenomena/*immunology ; Dysbiosis/microbiology ; Gastrointestinal Microbiome/*immunology ; Host Microbial Interactions/*immunology/physiology ; Humans ; Inflammation/microbiology ; Inflammatory Bowel Diseases/microbiology ; Obesity/microbiology ; Symbiosis/*physiology ; }, abstract = {The human gut microbiota is increasingly recognized for its important or even decisive role in health. As it becomes clear that microbiota and host mutually affect and depend on each other in an intimate relationship, a holistic view of the gut microbiota-host association imposes itself. Ideally, a stable state of equilibrium, homeostasis, is maintained and serves health, but signs are that perturbation of this equilibrium beyond the limits of resilience can propel the system into an alternative stable state, a pre-disease state, more susceptible to the development of chronic diseases. The microbiota-host equilibrium of a large and growing proportion of individuals in Western society may represent such a pre-disease state and explain the explosive development of chronic diseases such as inflammatory bowel disease, obesity, and other inflammatory diseases. These diseases themselves represent other alternative stable states again and are therefore hard to cure. The holistic view of the microbiota-host association where feedback loops between microbiota and host are thought to maintain the system in a stable state-be it a healthy, pre-disease, or disease state-implies that integrated approaches, addressing host processes and microbiota, should be used to treat or prevent (pre-)disease.}, } @article {pmid29716548, year = {2018}, author = {Law, WD and Fogarty, EA and Vester, A and Antonellis, A}, title = {A genome-wide assessment of conserved SNP alleles reveals a panel of regulatory SNPs relevant to the peripheral nerve.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {311}, pmid = {29716548}, issn = {1471-2164}, support = {F31 NS103378/NS/NINDS NIH HHS/United States ; R01 NS073748/NS/NINDS NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; }, mesh = {*Alleles ; Animals ; Gene Expression Regulation/genetics ; *Genomics ; Humans ; Mice ; Motor Neurons/metabolism ; Muscle Cells/metabolism ; Peripheral Nerves/cytology/*metabolism ; *Polymorphism, Single Nucleotide ; SOXE Transcription Factors/metabolism ; Schwann Cells/metabolism ; Tubulin/metabolism ; }, abstract = {BACKGROUND: Identifying functional non-coding variation is critical for defining the genetic contributions to human disease. While single-nucleotide polymorphisms (SNPs) within cis-acting transcriptional regulatory elements have been implicated in disease pathogenesis, not all cell types have been assessed and functional validations have been limited. In particular, the cells of the peripheral nervous system have been excluded from genome-wide efforts to link non-coding SNPs to altered gene function. Addressing this gap is essential for defining the genetic architecture of diseases that affect the peripheral nerve. We developed a computational pipeline to identify SNPs that affect regulatory function (rSNPs) and evaluated our predictions on a set of 144 regions in Schwann cells, motor neurons, and muscle cells.

RESULTS: We identified 28 regions that display regulatory activity in at least one cell type and 13 SNPs that affect regulatory function. We then tailored our pipeline to one peripheral nerve cell type by incorporating SOX10 ChIP-Seq data; SOX10 is essential for Schwann cells. We prioritized 22 putative SOX10 response elements harboring a SNP and rapidly validated two rSNPs. We then selected one of these elements for further characterization to assess the biological relevance of our approach. Deletion of the element from the genome of cultured Schwann cells-followed by differential gene expression studies-revealed Tubb2b as a candidate target gene. Studying the enhancer in developing mouse embryos revealed activity in SOX10-positive cells including the dorsal root ganglia and melanoblasts.

CONCLUSIONS: Our efforts provide insight into the utility of employing strict conservation for rSNP discovery. This strategy, combined with functional analyses, can yield candidate target genes. In support of this, our efforts suggest that investigating the role of Tubb2b in SOX10-positive cells may reveal novel biology within these cell populations.}, } @article {pmid29716547, year = {2018}, author = {Willson, NL and Forder, REA and Tearle, R and Williams, JL and Hughes, RJ and Nattrass, GS and Hynd, PI}, title = {Transcriptional analysis of liver from chickens with fast (meat bird), moderate (F1 layer x meat bird cross) and low (layer bird) growth potential.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {309}, pmid = {29716547}, issn = {1471-2164}, mesh = {Animals ; Chickens/*genetics/*growth & development ; *Gene Expression Profiling ; *Hybridization, Genetic ; Liver/*metabolism ; *Meat ; Phenotype ; }, abstract = {BACKGROUND: Divergent selection for meat and egg production in poultry has resulted in strains of birds differing widely in traits related to these products. Modern strains of meat birds can reach live weights of 2 kg in 35 d, while layer strains are now capable of producing more than 300 eggs per annum but grow slowly. In this study, RNA-Seq was used to investigate hepatic gene expression between three groups of birds with large differences in growth potential; meat bird, layer strain as well as an F1 layer x meat bird. The objective was to identify differentially expressed (DE) genes between all three strains to elucidate biological factors underpinning variations in growth performance.

RESULTS: RNA-Seq analysis was carried out on total RNA extracted from the liver of meat bird (n = 6), F1 layer x meat bird cross (n = 6) and layer strain (n = 6), males. Differential expression of genes were considered significant at P < 0.05, and a false discovery rate of < 0.05, with any fold change considered. In total, 6278 genes were found to be DE with 5832 DE between meat birds and layers (19%), 2935 DE between meat birds and the cross (9.6%) and 493 DE between the cross and layers (1.6%). Comparisons between the three groups identified 155 significant DE genes. Gene ontology (GO) enrichment and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analysis of the 155 DE genes showed the FoxO signalling pathway was most enriched (P = 0.001), including genes related to cell cycle regulation and insulin signalling. Significant GO terms included 'positive regulation of glucose import' and 'cellular response to oxidative stress', which is also consistent with FoxOs regulation of glucose metabolism. There were high correlations between FoxO pathway genes and bodyweight, as well as genes related to glycolysis and bodyweight.

CONCLUSIONS: This study revealed large transcriptome differences between meat and layer birds. There was significant evidence implicating the FoxO signalling pathway (via cell cycle regulation and altered metabolism) as an active driver of growth variations in chicken. Functional analysis of the FoxO genes is required to understand how they regulate growth and egg production.}, } @article {pmid29716542, year = {2018}, author = {Liu, X and Wang, Y and Liang, J and Wang, L and Qin, N and Zhao, Y and Zhao, G}, title = {In-depth comparative analysis of malaria parasite genomes reveals protein-coding genes linked to human disease in Plasmodium falciparum genome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {312}, pmid = {29716542}, issn = {1471-2164}, support = {31600615//National Natural Science Foundation of China/ ; 2016JQ8023//Natural Science Foundation of Shaanxi Province/ ; 2015M582796//China Postdoctoral Science Foundation/ ; }, mesh = {Erythrocytes/parasitology ; Genome, Protozoan/genetics ; *Genomics ; Humans ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/*genetics/pathogenicity/physiology ; Protozoan Proteins/*genetics ; Virulence/genetics ; }, abstract = {BACKGROUND: Plasmodium falciparum is the most virulent malaria parasite capable of parasitizing human erythrocytes. The identification of genes related to this capability can enhance our understanding of the molecular mechanisms underlying human malaria and lead to the development of new therapeutic strategies for malaria control. With the availability of several malaria parasite genome sequences, performing computational analysis is now a practical strategy to identify genes contributing to this disease.

RESULTS: Here, we developed and used a virtual genome method to assign 33,314 genes from three human malaria parasites, namely, P. falciparum, P. knowlesi and P. vivax, and three rodent malaria parasites, namely, P. berghei, P. chabaudi and P. yoelii, to 4605 clusters. Each cluster consisted of genes whose protein sequences were significantly similar and was considered as a virtual gene. Comparing the enriched values of all clusters in human malaria parasites with those in rodent malaria parasites revealed 115 P. falciparum genes putatively responsible for parasitizing human erythrocytes. These genes are mainly located in the chromosome internal regions and participate in many biological processes, including membrane protein trafficking and thiamine biosynthesis. Meanwhile, 289 P. berghei genes were included in the rodent parasite-enriched clusters. Most are located in subtelomeric regions and encode erythrocyte surface proteins. Comparing cluster values in P. falciparum with those in P. vivax and P. knowlesi revealed 493 candidate genes linked to virulence. Some of them encode proteins present on the erythrocyte surface and participate in cytoadhesion, virulence factor trafficking, or erythrocyte invasion, but many genes with unknown function were also identified. Cerebral malaria is characterized by accumulation of infected erythrocytes at trophozoite stage in brain microvascular. To discover cerebral malaria-related genes, fast Fourier transformation (FFT) was introduced to extract genes highly transcribed at the trophozoite stage. Finally, 55 candidate genes were identified. Considering that parasite-infected erythrocyte surface protein 2 (PIESP2) contains gap-junction-related Neuromodulin_N domain and that anti-PIESP2 might provide protection against malaria, we chose PIESP2 for further experimental study.

CONCLUSIONS: Our analysis revealed a limited number of genes linked to human disease in P. falciparum genome. These genes could be interesting targets for further functional characterization.}, } @article {pmid29716534, year = {2018}, author = {Oliver, A and Kay, M and Cooper, KK}, title = {Comparative genomics of cocci-shaped Sporosarcina strains with diverse spatial isolation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {310}, pmid = {29716534}, issn = {1471-2164}, support = {P30 CA062203/CA/NCI NIH HHS/United States ; S10 OD010794/OD/NIH HHS/United States ; S10 RR025496/RR/NCRR NIH HHS/United States ; }, mesh = {DNA Methylation ; Genome, Bacterial/genetics ; *Genomics ; Phylogeny ; Spatial Analysis ; Sporosarcina/*genetics ; Synteny ; }, abstract = {BACKGROUND: Cocci-shaped Sporosarcina strains are currently one of the few known cocci-shaped spore-forming bacteria, yet we know very little about the genomics. The goal of this study is to utilize comparative genomics to investigate the diversity of cocci-shaped Sporosarcina strains that differ in their geographical isolation and show different nutritional requirements.

RESULTS: For this study, we sequenced 28 genomes of cocci-shaped Sporosarcina strains isolated from 13 different locations around the world. We generated the first six complete genomes and methylomes utilizing PacBio sequencing, and an additional 22 draft genomes using Illumina sequencing. Genomic analysis revealed that cocci-shaped Sporosarcina strains contained an average genome of 3.3 Mb comprised of 3222 CDS, 54 tRNAs and 6 rRNAs, while only two strains contained plasmids. The cocci-shaped Sporosarcina genome on average contained 2.3 prophages and 15.6 IS elements, while methylome analysis supported the diversity of these strains as only one of 31 methylation motifs were shared under identical growth conditions. Analysis with a 90% identity cut-off revealed 221 core genes or ~ 7% of the genome, while a 30% identity cut-off generated a pan-genome of 8610 genes. The phylogenetic relationship of the cocci-shaped Sporosarcina strains based on either core genes, accessory genes or spore-related genes consistently resulted in the 29 strains being divided into eight clades.

CONCLUSIONS: This study begins to unravel the phylogenetic relationship of cocci-shaped Sporosarcina strains, and the comparative genomics of these strains supports identification of several new species.}, } @article {pmid29716533, year = {2018}, author = {Zhou, Y and Connor, EE and Wiggans, GR and Lu, Y and Tempelman, RJ and Schroeder, SG and Chen, H and Liu, GE}, title = {Genome-wide copy number variant analysis reveals variants associated with 10 diverse production traits in Holstein cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {314}, pmid = {29716533}, issn = {1471-2164}, support = {8042-31320-077-00-D//Agricultural Research Service/ ; 8042-31000-104-00-D//Agricultural Research Service/ ; 2011-68004-30340//National Institute of Food and Agriculture/ ; }, mesh = {Animals ; Cattle/*genetics/metabolism ; DNA Copy Number Variations/*genetics ; Female ; Fertility/genetics ; *Genomics ; Genotyping Techniques ; Milk/metabolism ; Phenotype ; Polymorphism, Single Nucleotide ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: Copy number variation (CNV) is an important type of genetic variation contributing to phenotypic differences among mammals and may serve as an alternative molecular marker to single nucleotide polymorphism (SNP) for genome-wide association study (GWAS). Recently, GWAS analysis using CNV has been applied in livestock, although few studies have focused on Holstein cattle.

RESULTS: We describe 191 CNV detected using intensity data from over 700,000 SNP genotypes generated with the BovineHD Genotyping BeadChip (Illumina, San Diego, CA) in 528 Holstein cows. The CNV were used for GWAS analysis of 10 important production traits of 473 cattle related to feed intake, milk quality, and female fertility, as well as 2 composite traits of net merit and productive life. In total, we detected 57 CNV associated (P < 0.05 after false discovery rate correction) with at least one of the 10 phenotypes. Focusing on feed efficiency and intake-related phenotypes of residual feed intake and dry matter intake, we detected a single CNV associated with both traits which overlaps a predicted olfactory receptor gene OR2A2 (LOC787786). Additionally, 2 CNV within the RXFP4 (relaxin/insulin like family peptide receptor 4) and 2 additional olfactory receptor gene regions, respectively, were associated with residual feed intake. The RXFP4 gene encodes a receptor for an orexigenic peptide, insulin-like peptide 5 produced by intestinal L cells, which is expressed by enteric neurons. Olfactory receptors are critical for transmitting the effects of odorants, contributing to the sense of smell, and have been implicated in participating in appetite regulation.

CONCLUSIONS: Our results identify CNV for genomic evaluation in Holstein cattle, and provide candidate genes, such as RXFP4, contributing to variation in feed efficiency and feed intake-related traits. These results indicate potential novel targets for manipulating feed intake-related traits of livestock.}, } @article {pmid29716522, year = {2018}, author = {Shapiro, M and Meier, S and MacCarthy, T}, title = {The cytidine deaminase under-representation reporter (CDUR) as a tool to study evolution of sequences under deaminase mutational pressure.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {163}, pmid = {29716522}, issn = {1471-2105}, support = {R01 AI132507/AI/NIAID NIH HHS/United States ; R01 GM111741/GM/NIGMS NIH HHS/United States ; 1R01GM111741/NH/NIH HHS/United States ; }, mesh = {APOBEC-3G Deaminase/*genetics ; B-Lymphocytes/metabolism ; *Biological Evolution ; DNA-Binding Proteins/*genetics ; *Genes, Reporter ; Germinal Center ; Humans ; *Mutation ; Oncogene Proteins, Viral/*genetics ; Software ; Viral Proteins/*genetics ; }, abstract = {BACKGROUND: Activation induced deaminase (AID) and apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (APOBEC3) are deaminases that mutate C to U on single-stranded DNA (ssDNA). AID is expressed primarily in germinal center B-cells, where it facilitates affinity maturation and class-switch recombination. APOBEC3 are a family of anti-viral proteins that act as part of the intrinsic immune response. In both cases, there are particular sequence motifs, also known as "mutation motifs", to which these deaminases prefer to bind and mutate.

RESULTS: We present a program, the cytidine deaminase under-representation reporter (CDUR) designed to statistically determine whether a given sequence has an under/over-representation of these mutation motifs. CDUR shows consitency with other studies of mutation motifs, as we show by analyzing sequences from the adeno-associated virus 2 (AAV2) and human papillomavirus (HPV).

CONCLUSION: Using various shuffling mechanisms to generate different null model distributions, we can tailor CDUR to correct for metrics such as GC-content, dinucleotide frequency, and codon bias.}, } @article {pmid29716521, year = {2018}, author = {Cairns, SD and Wirshing, HH}, title = {A phylogenetic analysis of the Primnoidae (Anthozoa: Octocorallia: Calcaxonia) with analyses of character evolution and a key to the genera and subgenera.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {66}, pmid = {29716521}, issn = {1471-2148}, mesh = {Animals ; Anthozoa/anatomy & histology/*classification/genetics ; Bayes Theorem ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: Previous phylogenetic analyses of primnoid octocorals utilizing morphological or molecular data have each recovered evolutionary relationships among genera that are largely incongruent with each other, with some exceptions. In an effort to reconcile molecular-based phylogenies with morphological characters, phylogenetic reconstructions were performed with 33 of 43 primnoid genera using four loci (mtMutS, COI, 28S and 18S), and ancestral state reconstructions were performed using 9 taxonomically relevant characters. In addition, an updated illustrated key to the current 48 genus-level (43 genera, 5 subgenera) primnoids is presented.

RESULTS: Ancestral state reconstruction recovered the ancestral colony shape of primnoids as dichotomous planar. Convergence was detected among all 9 characters, and reversals to the character state of the common ancestor occurred in 4 characters. However, some characters were found to be informative. For example, the weak ascus scale of Metafannyella is not likely homologous to the ascus scales of Onogorgia and Fannyella, and the monophyly of two subgenera within Thouarella, which contain polyps in either whorls or an isolated arrangement, was supported. Phylogenetic analyses were generally consistent with previous studies, and resulted in the synonymy of one genus and a subgenus, the elevation of two subgenera, and the transfer of two species back to an original genus. For example, body wall ornamentation of Fanellia was re-evaluated, indicating a synonymy with Callogorgia; the utility of polyp arrangement for the subgenus Plumarella (Dicholaphis) was not supported, and is synonymized with the nominate subgenus Plumarella (Plumarella); the subgenera Plumarella (Faxiella) and Plumarella (Verticillata) are raised to generic status; and the two Plumarella species (P. diadema and P. undulata) are transferred back to Thouarella based on the homology of their marginal scales.

CONCLUSIONS: Altogether, and similar to other octocorallian groups, these results indicate that many of the morphological characters examined among primnoids, particularly colony morphology, are labile and exhibit complex evolutionary histories. However, some morphological characters such as coordination of polyps, presence of the ascus body wall scale, number of rows of body wall scales, and number of marginal scales help identify many clades, and are suitable for robust systematic assessments among primnoids.}, } @article {pmid29716520, year = {2018}, author = {Jangid, RK and Kelkar, A and Muley, VY and Galande, S}, title = {Bidirectional promoters exhibit characteristic chromatin modification signature associated with transcription elongation in both sense and antisense directions.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {313}, pmid = {29716520}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Chromatin/*genetics ; Genes, Reporter/genetics ; Genomics ; Histones/genetics ; Humans ; Promoter Regions, Genetic/*genetics ; Transcription, Genetic/*genetics ; }, abstract = {BACKGROUND: In contrast to unidirectional promoters wherein antisense transcription results in short transcripts which are rapidly degraded, bidirectional promoters produce mature transcripts in both sense and antisense orientation. To understand the molecular mechanism of how productive bidirectional transcription is regulated, we focused on delineating the chromatin signature of bidirectional promoters.

RESULTS: We report generation and utility of a reporter system that enables simultaneous scoring of transcriptional activity in opposite directions. Testing of putative bidirectional promoters in this system demonstrates no measurable bias towards any one direction of transcription. We analyzed the NUP26L-PIH1D3 bidirectional gene pair during Retinoic acid mediated differentiation of embryonic carcinoma cells. In their native context, we observed that the chromatin landscape at and around the transcription regulatory region between the pair of bidirectional genes is modulated in concordance with transcriptional activity of each gene in the pair. We then extended this analysis to 974 bidirectional gene pairs in two different cell lines, H1 human embryonic stem cells and CD4 positive T cells using publicly available ChIP-Seq and RNA-Seq data. Bidirectional gene pairs were classified based on the intergenic distance separating the two TSS of the transcripts analyzed as well as the relative expression of each transcript in a bidirectional gene pair. We report that for the entire range of intergenic distance separating bidirectional genes, the expression profile of such genes (symmetric or asymmetric) matches the histone modification profile of marks associated with active transcription initiation and elongation.

CONCLUSIONS: We demonstrate unique distribution of histone modification marks that correlate robustly with the transcription status of genes regulated by bidirectional promoters. These findings strongly imply that occurrence of these marks might signal the transcription machinery to drive maturation of antisense transcription from the bidirectional promoters.}, } @article {pmid29716518, year = {2018}, author = {Menardo, F and Loiseau, C and Brites, D and Coscolla, M and Gygli, SM and Rutaihwa, LK and Trauner, A and Beisel, C and Borrell, S and Gagneux, S}, title = {Treemmer: a tool to reduce large phylogenetic datasets with minimal loss of diversity.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {164}, pmid = {29716518}, issn = {1471-2105}, support = {309540//European Research Council/International ; 310030_166687, IZRJZ3_164171 and IZLSZ3_170834//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; 309540-EVODRTB//European Research Council/International ; }, mesh = {Algorithms ; Computational Biology/*methods ; Databases, Genetic ; Humans ; Influenza A virus/*genetics ; Information Storage and Retrieval ; Mycobacterium tuberculosis/*genetics ; *Phylogeny ; *Software ; }, abstract = {BACKGROUND: Large sequence datasets are difficult to visualize and handle. Additionally, they often do not represent a random subset of the natural diversity, but the result of uncoordinated and convenience sampling. Consequently, they can suffer from redundancy and sampling biases.

RESULTS: Here we present Treemmer, a simple tool to evaluate the redundancy of phylogenetic trees and reduce their complexity by eliminating leaves that contribute the least to the tree diversity.

CONCLUSIONS: Treemmer can reduce the size of datasets with different phylogenetic structures and levels of redundancy while maintaining a sub-sample that is representative of the original diversity. Additionally, it is possible to fine-tune the behavior of Treemmer including any kind of meta-information, making Treemmer particularly useful for empirical studies.}, } @article {pmid29716400, year = {2018}, author = {}, title = {Corrigendum.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918773152}, doi = {10.1177/1474704918773152}, pmid = {29716400}, issn = {1474-7049}, } @article {pmid29715461, year = {2018}, author = {Galli, LM and Santana, F and Apollon, C and Szabo, LA and Ngo, K and Burrus, LW}, title = {Direct visualization of the Wntless-induced redistribution of WNT1 in developing chick embryos.}, journal = {Developmental biology}, volume = {439}, number = {2}, pages = {53-64}, pmid = {29715461}, issn = {1095-564X}, support = {P20 MD000262/MD/NIMHD NIH HHS/United States ; T34 GM008574/GM/NIGMS NIH HHS/United States ; }, mesh = {Acyltransferases/metabolism ; Animals ; Chick Embryo ; Chickens/metabolism ; Ectoderm/metabolism ; Embryo, Nonmammalian/metabolism ; Embryonic Development/physiology ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental/genetics ; Green Fluorescent Proteins ; Intracellular Signaling Peptides and Proteins/metabolism ; Lipoylation ; Membrane Proteins/metabolism ; Mice ; Neural Crest/metabolism ; Optical Imaging/*methods ; Protein Processing, Post-Translational ; Wnt Signaling Pathway/genetics/physiology ; Wnt1 Protein/*metabolism/physiology ; Wnt3A Protein/metabolism ; Zebrafish/metabolism ; }, abstract = {Paracrine Wnt signals are critical regulators of cell proliferation, specification, and differentiation during embryogenesis. Consistent with the discovery that Wnt ligands are post-translationally modified with palmitoleate (a 16 carbon mono-unsaturated fatty acid), our studies show that the vast majority of bioavailable chick WNT1 (cWNT1) produced in stably transfected L cells is cell-associated. Thus, it seems unlikely that the WNT1 signal is propagated by diffusion alone. Unfortunately, the production and transport of vertebrate Wnt proteins has been exceedingly difficult to study as few antibodies are able to detect endogenous Wnt proteins and fixation is known to disrupt the architecture of cells and tissues. Furthermore, vertebrate Wnts have been extraordinarily refractory to tagging. To help overcome these obstacles, we have generated a number of tools that permit the detection of WNT1 in palmitoylation assays and the visualization of chick and zebrafish WNT1 in live cells and tissues. Consistent with previous studies in fixed cells, live imaging of cells and tissues with overexpressed cWNT1-moxGFP shows predominant localization of the protein to a reticulated network that is likely to be the endoplasmic reticulum. As PORCN and WLS are important upstream regulators of Wnt gradient formation, we also undertook the generation of mCherry-tagged variants of both proteins. While co-expression of PORCN-mCherry had no discernible effect on the localization of WNT1-moxGFP, co-expression of WLS-mCherry caused a marked redistribution of WNT1-moxGFP to the cell surface and cellular projections in cultured cells as well as in neural crest and surface ectoderm cells in developing chick embryos. Our studies further establish that the levels of WLS, and not PORCN, are rate limiting with respect to WNT1 trafficking.}, } @article {pmid29713988, year = {2018}, author = {Vitas, M and Dobovišek, A}, title = {In the Beginning was a Mutualism - On the Origin of Translation.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {2}, pages = {223-243}, pmid = {29713988}, issn = {1573-0875}, support = {P1-0055//Javna Agencija za Raziskovalno Dejavnost RS/ ; }, mesh = {*Evolution, Chemical ; *Evolution, Molecular ; *Origin of Life ; Protein Biosynthesis ; Proteins/*chemistry ; RNA/*chemistry ; Symbiosis ; }, abstract = {The origin of translation is critical for understanding the evolution of life, including the origins of life. The canonical genetic code is one of the most dominant aspects of life on this planet, while the origin of heredity is one of the key evolutionary transitions in living world. Why the translation apparatus evolved is one of the enduring mysteries of molecular biology. Assuming the hypothesis, that during the emergence of life evolution had to first involve autocatalytic systems which only subsequently acquired the capacity of genetic heredity, we propose and discuss possible mechanisms, basic aspects of the emergence and subsequent molecular evolution of translation and ribosomes, as well as enzymes as we know them today. It is possible, in this sense, to view the ribosome as a digital-to-analogue information converter. The proposed mechanism is based on the abilities and tendencies of short RNA and polypeptides to fold and to catalyse biochemical reactions. The proposed mechanism is in concordance with the hypothesis of a possible chemical co-evolution of RNA and proteins in the origin of the genetic code or even more generally at the early evolution of life on Earth. The possible abundance and availability of monomers at prebiotic conditions are considered in the mechanism. The hypothesis that early polypeptides were folding on the RNA scaffold is also considered and mutualism in molecular evolutionary development of RNA and peptides is favoured.}, } @article {pmid29713072, year = {2018}, author = {Goldup, S}, title = {Molecular machines swap rings.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {39-40}, doi = {10.1038/d41586-018-02732-5}, pmid = {29713072}, issn = {1476-4687}, } @article {pmid29713071, year = {2018}, author = {Matthews, D}, title = {Virtual-reality applications give science a new dimension.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {127-128}, doi = {10.1038/d41586-018-04997-2}, pmid = {29713071}, issn = {1476-4687}, mesh = {Cell Nucleus/metabolism ; Humans ; Imaging, Three-Dimensional ; Information Dissemination ; Lysosomes/metabolism ; Microscopy, Confocal/*methods ; *Software/economics ; *Virtual Reality ; }, } @article {pmid29713069, year = {2018}, author = {Fan, Y}, title = {Data reviews quick to produce but open to abuse.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {31}, doi = {10.1038/d41586-018-05006-2}, pmid = {29713069}, issn = {1476-4687}, mesh = {*Data Accuracy ; *Meta-Analysis as Topic ; Publishing ; *Review Literature as Topic ; }, } @article {pmid29713068, year = {2018}, author = {Fuso Nerini, F}, title = {Shore up support for climate action using SDGs.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {31}, doi = {10.1038/d41586-018-05007-1}, pmid = {29713068}, issn = {1476-4687}, mesh = {Climate ; *Climate Change ; Economic Development ; *Goals ; }, } @article {pmid29713067, year = {2018}, author = {Calvo, RA and Peters, D}, title = {AI surveillance studies need ethics review.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {31}, doi = {10.1038/d41586-018-05015-1}, pmid = {29713067}, issn = {1476-4687}, mesh = {*Artificial Intelligence ; *Ethics ; *Population Surveillance ; Time Factors ; }, } @article {pmid29713066, year = {2018}, author = {Losada, S and Terras, P}, title = {Sea-bed mining - count the true costs.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {31}, doi = {10.1038/d41586-018-05016-0}, pmid = {29713066}, issn = {1476-4687}, mesh = {Animals ; *Biodiversity ; Conservation of Natural Resources/economics/*legislation & jurisprudence ; Environmental Policy/economics/*legislation & jurisprudence ; Geologic Sediments/*chemistry ; Mining/economics/*legislation & jurisprudence ; *Oceans and Seas ; Recycling/economics/legislation & jurisprudence ; }, } @article {pmid29713065, year = {2018}, author = {Bains, W}, title = {Nobel prize lagged my undergraduate lectures by 20 years.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {31}, doi = {10.1038/d41586-018-05017-z}, pmid = {29713065}, issn = {1476-4687}, mesh = {History, 20th Century ; *Nobel Prize ; *Students ; }, } @article {pmid29713064, year = {2018}, author = {Crossley, MP and Cimprich, KA}, title = {Faulty replication can sting.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {34-35}, doi = {10.1038/d41586-018-02804-6}, pmid = {29713064}, issn = {1476-4687}, mesh = {*DNA Replication ; *Inflammation ; Nucleotidyltransferases ; SAM Domain and HD Domain-Containing Protein 1/*physiology ; }, } @article {pmid29713063, year = {2018}, author = {Schneeberger, S}, title = {Life of a liver awaiting transplantation.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {40-41}, doi = {10.1038/d41586-018-04458-w}, pmid = {29713063}, issn = {1476-4687}, mesh = {Humans ; Liver/*physiology ; *Liver Transplantation ; }, } @article {pmid29713014, year = {2018}, author = {Raymond, O and Gouzy, J and Just, J and Badouin, H and Verdenaud, M and Lemainque, A and Vergne, P and Moja, S and Choisne, N and Pont, C and Carrère, S and Caissard, JC and Couloux, A and Cottret, L and Aury, JM and Szécsi, J and Latrasse, D and Madoui, MA and François, L and Fu, X and Yang, SH and Dubois, A and Piola, F and Larrieu, A and Perez, M and Labadie, K and Perrier, L and Govetto, B and Labrousse, Y and Villand, P and Bardoux, C and Boltz, V and Lopez-Roques, C and Heitzler, P and Vernoux, T and Vandenbussche, M and Quesneville, H and Boualem, A and Bendahmane, A and Liu, C and Le Bris, M and Salse, J and Baudino, S and Benhamed, M and Wincker, P and Bendahmane, M}, title = {The Rosa genome provides new insights into the domestication of modern roses.}, journal = {Nature genetics}, volume = {50}, number = {6}, pages = {772-777}, pmid = {29713014}, issn = {1546-1718}, support = {341076//European Research Council/International ; }, abstract = {Roses have high cultural and economic importance as ornamental plants and in the perfume industry. We report the rose whole-genome sequencing and assembly and resequencing of major genotypes that contributed to rose domestication. We generated a homozygous genotype from a heterozygous diploid modern rose progenitor, Rosa chinensis 'Old Blush'. Using single-molecule real-time sequencing and a meta-assembly approach, we obtained one of the most comprehensive plant genomes to date. Diversity analyses highlighted the mosaic origin of 'La France', one of the first hybrids combining the growth vigor of European species and the recurrent blooming of Chinese species. Genomic segments of Chinese ancestry identified new candidate genes for recurrent blooming. Reconstructing regulatory and secondary metabolism pathways allowed us to propose a model of interconnected regulation of scent and flower color. This genome provides a foundation for understanding the mechanisms governing rose traits and should accelerate improvement in roses, Rosaceae and ornamentals.}, } @article {pmid29713013, year = {2018}, author = {Burgess, DJ}, title = {Tracing cell-lineage histories.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {327}, doi = {10.1038/s41576-018-0015-0}, pmid = {29713013}, issn = {1471-0064}, } @article {pmid29713012, year = {2018}, author = {Scheckel, C and Aguzzi, A}, title = {Prions, prionoids and protein misfolding disorders.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {405-418}, doi = {10.1038/s41576-018-0011-4}, pmid = {29713012}, issn = {1471-0064}, abstract = {Prion diseases are progressive, incurable and fatal neurodegenerative conditions. The term 'prion' was first nominated to express the revolutionary concept that a protein could be infectious. We now know that prions consist of PrPSc, the pathological aggregated form of the cellular prion protein PrPC. Over the years, the term has been semantically broadened to describe aggregates irrespective of their infectivity, and the prion concept is now being applied, perhaps overenthusiastically, to all neurodegenerative diseases that involve protein aggregation. Indeed, recent studies suggest that prion diseases (PrDs) and protein misfolding disorders (PMDs) share some common disease mechanisms, which could have implications for potential treatments. Nevertheless, the transmissibility of bona fide prions is unique, and PrDs should be considered as distinct from other PMDs.}, } @article {pmid29712984, year = {2018}, author = {Boyd, IL}, title = {An inside view on pesticide policy.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {920-921}, doi = {10.1038/s41559-018-0557-8}, pmid = {29712984}, issn = {2397-334X}, } @article {pmid29712878, year = {2018}, author = {Berg, J and Campbell, P and Kiermer, V and Raikhel, N and Sweet, D}, title = {Joint statement on EPA proposed rule and public availability of data.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {}, doi = {10.1126/science.aau0116}, pmid = {29712878}, issn = {1095-9203}, mesh = {*Information Dissemination ; United States ; *United States Environmental Protection Agency ; }, } @article {pmid29712872, year = {2018}, author = {Pan, PL and Ye, YX and Lou, YH and Lu, JB and Cheng, C and Shen, Y and Moussian, B and Zhang, CX}, title = {A comprehensive omics analysis and functional survey of cuticular proteins in the brown planthopper.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5175-5180}, pmid = {29712872}, issn = {1091-6490}, mesh = {Animals ; Genetic Variation ; Hemiptera/*genetics/growth & development ; Insect Proteins/antagonists & inhibitors/*genetics/metabolism ; *Multigene Family ; *RNA Interference ; *Transcriptome ; }, abstract = {Cuticle, mainly composed of chitin and cuticular proteins (CPs), is a multifunctional structure of arthropods. CPs usually account for >1% of the total insect proteins. Why does an insect encode so many different CP genes in the genome? In this study, we use comprehensive large-scale technologies to study the full complement of CPs (i.e., the CP-ome) of the brown planthopper (BPH), Nilaparvata lugens, a major rice plant pest. Eight CP families (CPR, CPF, TWDL, CPLCP, CPG, CPAP1, CPAP3, and CPAPn) including 140 proteins in BPH, in which CPAPn is a CP family that we discovered. The CPG family that was considered to be restricted to the Lepidoptera has also been identified in BPH. As reported here, CPLCP family members are characterized by three conserved sequence motifs. In addition, we identified a testis protein family with a peritrophin A domain that we named TPAP. We authenticated the real existence of 106 proteins among the 140 CPs. RNA interference (RNAi) experiments were conducted against 135 CP genes in early- and late-instar nymphs and newly emerged female adults, demonstrating that 32 CPs were essential for BPH normal development or egg production. Combined RNAi experiments suggested redundant and complementary functions of the large number of CPs. Transcriptomic data revealed that the CP genes were expressed in a tissue-specific manner, and there were four clusters of developmental expression patterns. This study gives a comprehensive understanding of the roles of CPs in an insect cuticle.}, } @article {pmid29712871, year = {2018}, author = {Jungenitz, T and Beining, M and Radic, T and Deller, T and Cuntz, H and Jedlicka, P and Schwarzacher, SW}, title = {Structural homo- and heterosynaptic plasticity in mature and adult newborn rat hippocampal granule cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4670-E4679}, pmid = {29712871}, issn = {1091-6490}, mesh = {Animals ; Animals, Newborn ; Cells, Cultured ; Cytoplasmic Granules/*metabolism ; Dendritic Spines/*physiology ; Electric Stimulation ; Hippocampus/*cytology/*physiology ; Long-Term Potentiation ; Male ; Models, Neurological ; Neuronal Plasticity/*physiology ; Neurons/cytology/*physiology ; Rats ; Rats, Sprague-Dawley ; Synapses/*physiology ; }, abstract = {Adult newborn hippocampal granule cells (abGCs) contribute to spatial learning and memory. abGCs are thought to play a specific role in pattern separation, distinct from developmentally born mature GCs (mGCs). Here we examine at which exact cell age abGCs are synaptically integrated into the adult network and which forms of synaptic plasticity are expressed in abGCs and mGCs. We used virus-mediated labeling of abGCs and mGCs to analyze changes in spine morphology as an indicator of plasticity in rats in vivo. High-frequency stimulation of the medial perforant path induced long-term potentiation in the middle molecular layer (MML) and long-term depression in the nonstimulated outer molecular layer (OML). This stimulation protocol elicited NMDA receptor-dependent homosynaptic spine enlargement in the MML and heterosynaptic spine shrinkage in the inner molecular layer and OML. Both processes were concurrently present on individual dendritic trees of abGCs and mGCs. Spine shrinkage counteracted spine enlargement and thus could play a homeostatic role, normalizing synaptic weights. Structural homosynaptic spine plasticity had a clear onset, appearing in abGCs by 28 d postinjection (dpi), followed by heterosynaptic spine plasticity at 35 dpi, and at 77 dpi was equally as present in mature abGCs as in mGCs. From 35 dpi on, about 60% of abGCs and mGCs showed significant homo- and heterosynaptic plasticity on the single-cell level. This demonstration of structural homo- and heterosynaptic plasticity in abGCs and mGCs defines the time course of the appearance of synaptic plasticity and integration for abGCs.}, } @article {pmid29712870, year = {2018}, author = {Krishna Kumar, R and Mishchenko, A and Chen, X and Pezzini, S and Auton, GH and Ponomarenko, LA and Zeitler, U and Eaves, L and Fal'ko, VI and Geim, AK}, title = {High-order fractal states in graphene superlattices.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5135-5139}, pmid = {29712870}, issn = {1091-6490}, abstract = {Graphene superlattices were shown to exhibit high-temperature quantum oscillations due to periodic emergence of delocalized Bloch states in high magnetic fields such that unit fractions of the flux quantum pierce a superlattice unit cell. Under these conditions, semiclassical electron trajectories become straight again, similar to the case of zero magnetic field. Here, we report magnetotransport measurements that reveal second-, third-, and fourth-order magnetic Bloch states at high electron densities and temperatures above 100 K. The recurrence of these states creates a fractal pattern intimately related to the origin of Hofstadter butterflies. The hierarchy of the fractal states is determined by the width of magnetic minibands, in qualitative agreement with our band-structure calculations.}, } @article {pmid29712869, year = {2018}, author = {Burton, JC and Amundson, JM and Cassotto, R and Kuo, CC and Dennin, M}, title = {Quantifying flow and stress in ice mélange, the world's largest granular material.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5105-5110}, pmid = {29712869}, issn = {1091-6490}, abstract = {Tidewater glacier fjords are often filled with a collection of calved icebergs, brash ice, and sea ice. For glaciers with high calving rates, this "mélange" of ice can be jam-packed, so that the flow of ice fragments is mostly determined by granular interactions. In the jammed state, ice mélange has been hypothesized to influence iceberg calving and capsize, dispersion and attenuation of ocean waves, injection of freshwater into fjords, and fjord circulation. However, detailed measurements of ice mélange are lacking due to difficulties in instrumenting remote, ice-choked fjords. Here we characterize the flow and associated stress in ice mélange, using a combination of terrestrial radar data, laboratory experiments, and numerical simulations. We find that, during periods of terminus quiescence, ice mélange experiences laminar flow over timescales of hours to days. The uniform flow fields are bounded by shear margins along fjord walls where force chains between granular icebergs terminate. In addition, the average force per unit width that is transmitted to the glacier terminus, which can exceed 107 N/m, increases exponentially with the mélange length-to-width ratio. These "buttressing" forces are sufficiently high to inhibit the initiation of large-scale calving events, supporting the notion that ice mélange can be viewed as a weak granular ice shelf that transmits stresses from fjord walls back to glacier termini.}, } @article {pmid29712868, year = {2018}, author = {Jian, X and Felsenfeld, G}, title = {Insulin promoter in human pancreatic β cells contacts diabetes susceptibility loci and regulates genes affecting insulin metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4633-E4641}, pmid = {29712868}, issn = {1091-6490}, mesh = {Cells, Cultured ; Chromosomes, Human, Pair 11/genetics/metabolism ; Diabetes Mellitus/genetics/*metabolism/pathology ; Disease Susceptibility ; Gene Expression Regulation/*drug effects ; Glucose/metabolism ; Humans ; Insulin/*genetics/metabolism ; Insulin Secretion ; Insulin-Secreting Cells/drug effects/*metabolism ; Oligonucleotides, Antisense/*pharmacology ; *Promoter Regions, Genetic ; Receptors, Somatostatin/antagonists & inhibitors/genetics/*metabolism ; Somatostatin-28/pharmacology ; }, abstract = {Both type 1 and type 2 diabetes involve a complex interplay between genetic, epigenetic, and environmental factors. Our laboratory has been interested in the physical interactions, in nuclei of human pancreatic β cells, between the insulin (INS) gene and other genes that are involved in insulin metabolism. We have identified, using Circularized Chromosome Conformation Capture (4C), many physical contacts in a human pancreatic β cell line between the INS promoter on chromosome 11 and sites on most other chromosomes. Many of these contacts are associated with type 1 or type 2 diabetes susceptibility loci. To determine whether physical contact is correlated with an ability of the INS locus to affect expression of these genes, we knock down INS expression by targeting the promoter; 259 genes are either up or down-regulated. Of these, 46 make physical contact with INS We analyze a subset of the contacted genes and show that all are associated with acetylation of histone H3 lysine 27, a marker of actively expressed genes. To demonstrate the usefulness of this approach in revealing regulatory pathways, we identify from among the contacted sites the previously uncharacterized gene SSTR5-AS1 and show that it plays an important role in controlling the effect of somatostatin-28 on insulin secretion. These results are consistent with models in which clustering of genes supports transcriptional activity. This may be a particularly important mechanism in pancreatic β cells and in other cells where a small subset of genes is expressed at high levels.}, } @article {pmid29712867, year = {2018}, author = {Tejero, JM and Belfer-Cohen, A and Bar-Yosef, O and Gutkin, V and Rabinovich, R}, title = {Symbolic emblems of the Levantine Aurignacians as a regional entity identifier (Hayonim Cave, Lower Galilee, Israel).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5145-5150}, pmid = {29712867}, issn = {1091-6490}, abstract = {The Levantine Aurignacian is a unique phenomenon in the local Upper Paleolithic sequence, showing greater similarity to the West European classic Aurignacian than to the local Levantine archaeological entities preceding and following it. Herewith we highlight another unique characteristic of this entity, namely, the presence of symbolic objects in the form of notched bones (mostly gazelle scapulae) from the Aurignacian levels of Hayonim Cave, Lower Galilee, Israel. Through both macroscopic and microscopic analyses of the items, we suggest that they are not mere cut marks but rather are intentional (decorative?) human-made markings. The significance of this evidence for symbolic behavior is discussed in its chrono-cultural and geographical contexts. Notched bones are among the oldest symbolic expressions of anatomically modern humans. However, unlike other Paleolithic sites where such findings were reported in single numbers, the number of these items recovered at Hayonim Cave is sufficient to assume they possibly served as an emblem of the Levantine Aurignacian.}, } @article {pmid29712866, year = {2018}, author = {Sah, P and Medlock, J and Fitzpatrick, MC and Singer, BH and Galvani, AP}, title = {Optimizing the impact of low-efficacy influenza vaccines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5151-5156}, pmid = {29712866}, issn = {1091-6490}, support = {U01 GM087719/GM/NIGMS NIH HHS/United States ; U01 GM105627/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Hospitalization/statistics & numerical data ; Humans ; Incidence ; Infant ; Infant, Newborn ; Influenza A virus/*immunology ; Influenza Vaccines/administration & dosage/*standards ; Influenza, Human/*economics/epidemiology/*prevention & control ; Middle Aged ; Morbidity ; Population Surveillance ; Resource Allocation/economics/legislation & jurisprudence/*standards ; Seasons ; Survival Rate ; United States/epidemiology ; Vaccination/*statistics & numerical data ; Young Adult ; }, abstract = {The efficacy of influenza vaccines varies from one year to the next, with efficacy during the 2017-2018 season anticipated to be lower than usual. However, the impact of low-efficacy vaccines at the population level and their optimal age-specific distribution have yet to be ascertained. Applying an optimization algorithm to a mathematical model of influenza transmission and vaccination in the United States, we determined the optimal age-specific uptake of low-efficacy vaccine that would minimize incidence, hospitalization, mortality, and disability-adjusted life-years (DALYs), respectively. We found that even relatively low-efficacy influenza vaccines can be highly impactful, particularly when vaccine uptake is optimally distributed across age groups. As vaccine efficacy declines, the optimal distribution of vaccine uptake shifts toward the elderly to minimize mortality and DALYs. Health practitioner encouragement and concerted recruitment efforts are required to achieve optimal coverage among target age groups, thereby minimizing influenza morbidity and mortality for the population overall.}, } @article {pmid29712865, year = {2018}, author = {Seo, A and Steinberg-Shemer, O and Unal, S and Casadei, S and Walsh, T and Gumruk, F and Shalev, S and Shimamura, A and Akarsu, NA and Tamary, H and King, MC}, title = {Mechanism for survival of homozygous nonsense mutations in the tumor suppressor gene BRCA1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5241-5246}, pmid = {29712865}, issn = {1091-6490}, support = {F30 DK103462/DK/NIDDK NIH HHS/United States ; R24 DK099808/DK/NIDDK NIH HHS/United States ; R35 CA197458/CA/NCI NIH HHS/United States ; T32 GM007266/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; *Alternative Splicing ; BRCA1 Protein/*genetics ; Breast Neoplasms/*genetics/pathology ; Child ; Child, Preschool ; *Codon, Nonsense ; Female ; *Homozygote ; Humans ; Ovarian Neoplasms/*genetics/pathology ; Pedigree ; }, abstract = {BRCA1 is essential for repair of DNA double-strand breaks by homologous recombination, and hence for survival. Complete loss of its function is lethal during early embryonic development. Patients who are compound heterozygous for BRCA1 truncating mutations and missense alleles that retain some DNA repair capacity may survive, albeit with very high risk of early onset breast or ovarian cancer and features of Fanconi anemia. However, a mechanism enabling survival of patients homozygous for BRCA1 truncating mutations has not been described. We studied two unrelated families in which four children presented with multiple congenital anomalies and severe chromosomal fragility. One child developed T cell acute lymphocytic leukemia (ALL), and a second child developed neuroblastoma. Each of the four children was homozygous for a nonsense mutation in BRCA1 exon 11. Homozygosity for the nonsense mutations was viable thanks to the presence of a naturally occurring alternative splice donor in BRCA1 exon 11 that lies 5' of the mutations. The mutations did not affect the alternative splice site, but transcription from it produced an in-frame BRCA1 message with deletion of 3,309 bp. The translated BRCA1 protein was only 40% of normal length, but with intact N- and C-terminal sequences. These patients extend the range of BRCA1-related phenotypes and illustrate how naturally occurring alternative splicing can enable survival, albeit with severe consequences, of otherwise lethal genotypes of an essential gene.}, } @article {pmid29712864, year = {2018}, author = {Fisher, MPA and Radzihovsky, L}, title = {Quantum indistinguishability in chemical reactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4551-E4558}, pmid = {29712864}, issn = {1091-6490}, abstract = {Quantum indistinguishability plays a crucial role in many low-energy physical phenomena, from quantum fluids to molecular spectroscopy. It is, however, typically ignored in most high-temperature processes, particularly for ionic coordinates, implicitly assumed to be distinguishable, incoherent, and thus well approximated classically. We explore enzymatic chemical reactions involving small symmetric molecules and argue that in many situations a full quantum treatment of collective nuclear degrees of freedom is essential. Supported by several physical arguments, we conjecture a "quantum dynamical selection" (QDS) rule for small symmetric molecules that precludes chemical processes that involve direct transitions from orbitally nonsymmetric molecular states. As we propose and discuss, the implications of the QDS rule include (i) a differential chemical reactivity of para- and orthohydrogen, (ii) a mechanism for inducing intermolecular quantum entanglement of nuclear spins, (iii) a mass-independent isotope fractionation mechanism, (iv) an explanation of the enhanced chemical activity of "reactive oxygen species", (v) illuminating the importance of ortho-water molecules in modulating the quantum dynamics of liquid water, and (vi) providing the critical quantum-to-biochemical linkage in the nuclear spin model of the (putative) quantum brain, among others.}, } @article {pmid29712863, year = {2018}, author = {Bérut, A and Chauvet, H and Legué, V and Moulia, B and Pouliquen, O and Forterre, Y}, title = {Gravisensors in plant cells behave like an active granular liquid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5123-5128}, pmid = {29712863}, issn = {1091-6490}, mesh = {*Biomimetics ; *Gravitropism ; Gravity Sensing/*physiology ; Plant Cells/*physiology ; *Plant Physiological Phenomena ; Solutions ; Triticum/*growth & development/physiology ; }, abstract = {Plants are able to sense and respond to minute tilt from the vertical direction of the gravity, which is key to maintain their upright posture during development. However, gravisensing in plants relies on a peculiar sensor made of microsize starch-filled grains (statoliths) that sediment and form tiny granular piles at the bottom of the cell. How such a sensor can detect inclination is unclear, as granular materials like sand are known to display flow threshold and finite avalanche angle due to friction and interparticle jamming. Here, we address this issue by combining direct visualization of statolith avalanches in plant cells and experiments in biomimetic cells made of microfluidic cavities filled with a suspension of heavy Brownian particles. We show that, despite their granular nature, statoliths move and respond to the weakest angle, as a liquid clinometer would do. Comparison between the biological and biomimetic systems reveals that this liquid-like behavior comes from the cell activity, which agitates statoliths with an apparent temperature one order of magnitude larger than actual temperature. Our results shed light on the key role of active fluctuations of statoliths for explaining the remarkable sensitivity of plants to inclination. Our study also provides support to a recent scenario of gravity perception in plants, by bridging the active granular rheology of statoliths at the microscopic level to the macroscopic gravitropic response of the plant.}, } @article {pmid29712862, year = {2018}, author = {Tan, CW and Peiffer, M and Hoover, K and Rosa, C and Acevedo, FE and Felton, GW}, title = {Symbiotic polydnavirus of a parasite manipulates caterpillar and plant immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5199-5204}, pmid = {29712862}, issn = {1091-6490}, mesh = {Animals ; Glucose Oxidase/metabolism ; Herbivory ; Host-Parasite Interactions/*immunology ; Larva/*immunology/parasitology/virology ; Lepidoptera/*immunology/parasitology/virology ; Lycopersicon esculentum/*immunology ; Plant Immunity/*immunology ; Polydnaviridae/*physiology ; Predatory Behavior ; Symbiosis ; Virus Integration ; Virus Replication ; Wasps/*physiology ; }, abstract = {Obligate symbioses occur when organisms require symbiotic relationships to survive. Some parasitic wasps of caterpillars possess obligate mutualistic viruses called "polydnaviruses." Along with eggs, wasps inject polydnavirus inside their caterpillar hosts where the hatching larvae develop inside the caterpillar. Polydnaviruses suppress the immune systems of their caterpillar hosts, which enables egg hatch and wasp larval development. It is unknown whether polydnaviruses also manipulate the salivary proteins of the caterpillar, which may affect the elicitation of plant defenses during feeding by the caterpillar. Here, we show that a polydnavirus of the parasitoid Microplitis croceipes, and not the parasitoid larva itself, drives the regulation of salivary enzymes of the caterpillar Helicoverpa zea that are known to elicit tomato plant-defense responses to herbivores. The polydnavirus suppresses glucose oxidase, which is a primary plant-defense elicitor in the saliva of the H. zea caterpillar. By suppressing plant defenses, the polydnavirus allows the caterpillar to grow at a faster rate, thus improving the host suitability for the parasitoid. Remarkably, polydnaviruses manipulate the phenotypes of the wasp, caterpillar, and host plant, demonstrating that polydnaviruses play far more prominent roles in shaping plant-herbivore interactions than ever considered.}, } @article {pmid29712861, year = {2018}, author = {Nelson, CS and Huffman, T and Jenks, JA and Cisneros de la Rosa, E and Xie, G and Vandergrift, N and Pass, RF and Pollara, J and Permar, SR}, title = {HCMV glycoprotein B subunit vaccine efficacy mediated by nonneutralizing antibody effector functions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6267-6272}, pmid = {29712861}, issn = {1091-6490}, support = {DP2 HD075699/HD/NICHD NIH HHS/United States ; F30 HD089577/HD/NICHD NIH HHS/United States ; R21 AI136556/AI/NIAID NIH HHS/United States ; }, mesh = {Adult ; Antibodies, Neutralizing/*immunology ; Antibodies, Viral/immunology ; Cells, Cultured ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/*immunology ; Cytomegalovirus Vaccines/*immunology ; Epitopes/immunology ; Female ; Humans ; Immunoglobulin G/immunology ; Polysorbates ; Squalene/immunology ; Vaccines, Subunit/*immunology ; Viral Envelope Proteins/*immunology ; Young Adult ; }, abstract = {Human cytomegalovirus (HCMV) is the most common congenital infection worldwide, frequently causing hearing loss and brain damage in afflicted infants. A vaccine to prevent maternal acquisition of HCMV during pregnancy is necessary to reduce the incidence of infant disease. The glycoprotein B (gB) + MF59 adjuvant subunit vaccine platform is the most successful HCMV vaccine tested to date, demonstrating ∼50% efficacy in preventing HCMV acquisition in multiple phase 2 trials. However, the mechanism of vaccine protection remains unknown. Plasma from 33 postpartum women gB/MF59 vaccinees at peak immunogenicity was tested for gB epitope specificity as well as neutralizing and nonneutralizing anti-HCMV effector functions and compared with an HCMV-seropositive cohort. gB/MF59 vaccination elicited IgG responses with gB-binding magnitude and avidity comparable to natural infection. Additionally, IgG subclass distribution was similar with predominant IgG1 and IgG3 responses induced by gB vaccination and HCMV infection. However, vaccine-elicited antibodies exhibited limited neutralization of the autologous virus, negligible neutralization of multiple heterologous strains, and limited binding responses against gB structural motifs targeted by neutralizing antibodies including AD-1, AD-2, and domain I. Vaccinees had high-magnitude IgG responses against AD-3 linear epitopes, demonstrating immunodominance against this nonneutralizing, cytosolic region. Finally, vaccine-elicited IgG robustly bound membrane-associated gB on the surface of transfected or HCMV-infected cells and mediated virion phagocytosis, although were poor mediators of NK cell activation. Altogether, these data suggest that nonneutralizing antibody functions, including virion phagocytosis, likely played a role in the observed 50% vaccine-mediated protection against HCMV acquisition.}, } @article {pmid29712860, year = {2018}, author = {Guillaume, P and Picaud, S and Baumgaertner, P and Montandon, N and Schmidt, J and Speiser, DE and Coukos, G and Bassani-Sternberg, M and Filippakopoulos, P and Gfeller, D}, title = {The C-terminal extension landscape of naturally presented HLA-I ligands.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5083-5088}, pmid = {29712860}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 092809/Z/10/Z//Wellcome Trust/United Kingdom ; 095751/Z/11/Z//Wellcome Trust/United Kingdom ; }, mesh = {Algorithms ; Amino Acid Sequence ; Antigen Presentation/*immunology ; Crystallography, X-Ray ; Epitopes, T-Lymphocyte/*immunology ; HLA Antigens/*immunology ; Humans ; Ligands ; Peptide Fragments/*immunology ; Protein Binding ; T-Lymphocytes/*immunology ; }, abstract = {HLA-I molecules play a central role in antigen presentation. They typically bind 9- to 12-mer peptides, and their canonical binding mode involves anchor residues at the second and last positions of their ligands. To investigate potential noncanonical binding modes, we collected in-depth and accurate HLA peptidomics datasets covering 54 HLA-I alleles and developed algorithms to analyze these data. Our results reveal frequent (442 unique peptides) and statistically significant C-terminal extensions for at least eight alleles, including the common HLA-A03:01, HLA-A31:01, and HLA-A68:01. High resolution crystal structure of HLA-A68:01 with such a ligand uncovers structural changes taking place to accommodate C-terminal extensions and helps unraveling sequence and structural properties predictive of the presence of these extensions. Scanning viral proteomes with the C-terminal extension motifs identifies many putative epitopes and we demonstrate direct recognition by human CD8+ T cells of a 10-mer epitope from cytomegalovirus predicted to follow the C-terminal extension binding mode.}, } @article {pmid29712859, year = {2018}, author = {Khait, I and Azaria, P and Hubig, C and Schollwöck, U and Auerbach, A}, title = {Doped Kondo chain, a heavy Luttinger liquid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5140-5144}, pmid = {29712859}, issn = {1091-6490}, abstract = {The doped 1D Kondo Lattice describes complex competition between itinerant and magnetic ordering. The numerically computed wave vector-dependent charge and spin susceptibilities give insights into its low-energy properties. Similar to the prediction of the large N approximation, gapless spin and charge modes appear at the large Fermi wave vector. The highly suppressed spin velocity is a manifestation of "heavy" Luttinger liquid quasiparticles. A low-energy hybridization gap is detected at the small (conduction band) Fermi wave vector. In contrast to the exponential suppression of the Fermi velocity in the large-N approximation, we fit the spin velocity by a density-dependent power law of the Kondo coupling. The differences between the large-N theory and our numerical results are associated with the emergent magnetic Ruderman-Kittel-Kasuya-Yosida interactions.}, } @article {pmid29712858, year = {2018}, author = {Liao, X and Shen, Y and Zhang, R and Sugi, K and Vasudevan, NT and Alaiti, MA and Sweet, DR and Zhou, L and Qing, Y and Gerson, SL and Fu, C and Wynshaw-Boris, A and Hu, R and Schwartz, MA and Fujioka, H and Richardson, B and Cameron, MJ and Hayashi, H and Stamler, JS and Jain, MK}, title = {Distinct roles of resident and nonresident macrophages in nonischemic cardiomyopathy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4661-E4669}, pmid = {29712858}, issn = {1091-6490}, support = {F30 HL139014/HL/NHLBI NIH HHS/United States ; R01 DK111468/DK/NIDDK NIH HHS/United States ; R35 HL135789/HL/NHLBI NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cardiomegaly/immunology/metabolism/*pathology ; Cardiomyopathies/immunology/metabolism/*pathology ; Cells, Cultured ; Heart Failure/immunology/metabolism/*pathology ; Kruppel-Like Transcription Factors/*metabolism ; Macrophages/immunology/metabolism/*pathology ; Mice ; Myocardium/immunology/metabolism/*pathology ; Pressure ; }, abstract = {Nonischemic cardiomyopathy (NICM) resulting from long-standing hypertension, valvular disease, and genetic mutations is a major cause of heart failure worldwide. Recent observations suggest that myeloid cells can impact cardiac function, but the role of tissue-intrinsic vs. tissue-extrinsic myeloid cells in NICM remains poorly understood. Here, we show that cardiac resident macrophage proliferation occurs within the first week following pressure overload hypertrophy (POH; a model of heart failure) and is requisite for the heart's adaptive response. Mechanistically, we identify Kruppel-like factor 4 (KLF4) as a key transcription factor that regulates cardiac resident macrophage proliferation and angiogenic activities. Finally, we show that blood-borne macrophages recruited in late-phase POH are detrimental, and that blockade of their infiltration improves myocardial angiogenesis and preserves cardiac function. These observations demonstrate previously unappreciated temporal and spatial roles for resident and nonresident macrophages in the development of heart failure.}, } @article {pmid29712857, year = {2018}, author = {Werner, GDA and Cornelissen, JHC and Cornwell, WK and Soudzilovskaia, NA and Kattge, J and West, SA and Kiers, ET}, title = {Symbiont switching and alternative resource acquisition strategies drive mutualism breakdown.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5229-5234}, pmid = {29712857}, issn = {1091-6490}, support = {335542//European Research Council/International ; }, mesh = {*Biological Evolution ; *Environment ; Feedback, Physiological ; Mycorrhizae/*physiology ; Plants/*microbiology ; Symbiosis/*physiology ; }, abstract = {Cooperative interactions among species, termed mutualisms, have played a crucial role in the evolution of life on Earth. However, despite key potential benefits to partners, there are many cases in which two species cease to cooperate and mutualisms break down. What factors drive the evolutionary breakdown of mutualism? We examined the pathways toward breakdowns of the mutualism between plants and arbuscular mycorrhizal fungi. By using a comparative approach, we identify ∼25 independent cases of complete mutualism breakdown across global seed plants. We found that breakdown of cooperation was only stable when host plants (i) partner with other root symbionts or (ii) evolve alternative resource acquisition strategies. Our results suggest that key mutualistic services are only permanently lost if hosts evolve alternative symbioses or adaptations.}, } @article {pmid29712856, year = {2018}, author = {Hollender, CA and Pascal, T and Tabb, A and Hadiarto, T and Srinivasan, C and Wang, W and Liu, Z and Scorza, R and Dardick, C}, title = {Loss of a highly conserved sterile alpha motif domain gene (WEEP) results in pendulous branch growth in peach trees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4690-E4699}, pmid = {29712856}, issn = {1091-6490}, support = {R21 MH078037/MH/NIMH NIH HHS/United States ; }, mesh = {Chromosome Mapping ; Phenotype ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Plant Roots/anatomy & histology/*growth & development/metabolism ; Plant Shoots/anatomy & histology/*growth & development/metabolism ; Protein Domains ; Prunus persica/anatomy & histology/*growth & development/metabolism ; *Sterile Alpha Motif ; Trees/anatomy & histology/*growth & development/metabolism ; }, abstract = {Plant shoots typically grow upward in opposition to the pull of gravity. However, exceptions exist throughout the plant kingdom. Most conspicuous are trees with weeping or pendulous branches. While such trees have long been cultivated and appreciated for their ornamental value, the molecular basis behind the weeping habit is not known. Here, we characterized a weeping tree phenotype in Prunus persica (peach) and identified the underlying genetic mutation using a genomic sequencing approach. Weeping peach tree shoots exhibited a downward elliptical growth pattern and did not exhibit an upward bending in response to 90° reorientation. The causative allele was found to be an uncharacterized gene, Ppa013325, having a 1.8-Kb deletion spanning the 5' end. This gene, dubbed WEEP, was predominantly expressed in phloem tissues and encodes a highly conserved 129-amino acid protein containing a sterile alpha motif (SAM) domain. Silencing WEEP in the related tree species Prunus domestica (plum) resulted in more outward, downward, and wandering shoot orientations compared to standard trees, supporting a role for WEEP in directing lateral shoot growth in trees. This previously unknown regulator of branch orientation, which may also be a regulator of gravity perception or response, provides insights into our understanding of how tree branches grow in opposition to gravity and could serve as a critical target for manipulating tree architecture for improved tree shape in agricultural and horticulture applications.}, } @article {pmid29712855, year = {2018}, author = {Frost, JM and Kim, MY and Park, GT and Hsieh, PH and Nakamura, M and Lin, SJH and Yoo, H and Choi, J and Ikeda, Y and Kinoshita, T and Choi, Y and Zilberman, D and Fischer, RL}, title = {FACT complex is required for DNA demethylation at heterochromatin during reproduction in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4720-E4729}, pmid = {29712855}, issn = {1091-6490}, support = {R01 GM069415/GM/NIGMS NIH HHS/United States ; S10 OD018174/OD/NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; }, mesh = {Arabidopsis/*genetics/growth & development/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Cell Nucleus ; *DNA Demethylation ; DNA, Plant ; Endosperm/metabolism ; *Gene Expression Regulation, Plant ; *Genomic Imprinting ; *Heterochromatin ; Ovule/genetics ; Plants, Genetically Modified/*genetics/growth & development/metabolism ; Pollen/genetics ; Transcription, Genetic ; }, abstract = {The DEMETER (DME) DNA glycosylase catalyzes genome-wide DNA demethylation and is required for endosperm genomic imprinting and embryo viability. Targets of DME-mediated DNA demethylation reside in small, euchromatic, AT-rich transposons and at the boundaries of large transposons, but how DME interacts with these diverse chromatin states is unknown. The STRUCTURE SPECIFIC RECOGNITION PROTEIN 1 (SSRP1) subunit of the chromatin remodeler FACT (facilitates chromatin transactions), was previously shown to be involved in the DME-dependent regulation of genomic imprinting in Arabidopsis endosperm. Therefore, to investigate the interaction between DME and chromatin, we focused on the activity of the two FACT subunits, SSRP1 and SUPPRESSOR of TY16 (SPT16), during reproduction in Arabidopsis We found that FACT colocalizes with nuclear DME in vivo, and that DME has two classes of target sites, the first being euchromatic and accessible to DME, but the second, representing over half of DME targets, requiring the action of FACT for DME-mediated DNA demethylation genome-wide. Our results show that the FACT-dependent DME targets are GC-rich heterochromatin domains with high nucleosome occupancy enriched with H3K9me2 and H3K27me1. Further, we demonstrate that heterochromatin-associated linker histone H1 specifically mediates the requirement for FACT at a subset of DME-target loci. Overall, our results demonstrate that FACT is required for DME targeting by facilitating its access to heterochromatin.}, } @article {pmid29712854, year = {2018}, author = {Lindén, A}, title = {Adaptive and nonadaptive changes in phenological synchrony.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5057-5059}, pmid = {29712854}, issn = {1091-6490}, mesh = {Animals ; *Climate Change ; Food Chain ; Population Dynamics ; *Seasons ; }, } @article {pmid29712853, year = {2018}, author = {Fereiro, JA and Yu, X and Pecht, I and Sheves, M and Cuevas, JC and Cahen, D}, title = {Tunneling explains efficient electron transport via protein junctions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4577-E4583}, pmid = {29712853}, issn = {1091-6490}, mesh = {Copper/*chemistry ; Electron Transport ; *Electrons ; Humans ; Metalloproteins/*chemistry ; *Models, Theoretical ; Temperature ; }, abstract = {Metalloproteins, proteins containing a transition metal ion cofactor, are electron transfer agents that perform key functions in cells. Inspired by this fact, electron transport across these proteins has been widely studied in solid-state settings, triggering the interest in examining potential use of proteins as building blocks in bioelectronic devices. Here, we report results of low-temperature (10 K) electron transport measurements via monolayer junctions based on the blue copper protein azurin (Az), which strongly suggest quantum tunneling of electrons as the dominant charge transport mechanism. Specifically, we show that, weakening the protein-electrode coupling by introducing a spacer, one can switch the electron transport from off-resonant to resonant tunneling. This is a consequence of reducing the electrode's perturbation of the Cu(II)-localized electronic state, a pattern that has not been observed before in protein-based junctions. Moreover, we identify vibronic features of the Cu(II) coordination sphere in transport characteristics that show directly the active role of the metal ion in resonance tunneling. Our results illustrate how quantum mechanical effects may dominate electron transport via protein-based junctions.}, } @article {pmid29712852, year = {2018}, author = {Spence, A and Purtha, W and Tam, J and Dong, S and Kim, Y and Ju, CH and Sterling, T and Nakayama, M and Robinson, WH and Bluestone, JA and Anderson, MS and Tang, Q}, title = {Revealing the specificity of regulatory T cells in murine autoimmune diabetes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5265-5270}, pmid = {29712852}, issn = {1091-6490}, support = {P01 AI118688/AI/NIAID NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; UC4 DK104223/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Autoantigens/immunology ; Autoimmune Diseases/*immunology/therapy ; Diabetes Mellitus, Type 1/*immunology/therapy ; *Disease Models, Animal ; Immune Tolerance/*immunology ; Insulin/*immunology ; Islets of Langerhans Transplantation/*immunology ; Mice, Inbred NOD ; Mice, SCID ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Regulatory T cells (Tregs) control organ-specific autoimmunity in a tissue antigen-specific manner, yet little is known about their specificity in a natural repertoire. In this study, we used the nonobese diabetic (NOD) mouse model of autoimmune diabetes to investigate the antigen specificity of Tregs present in the inflamed tissue, the islets of Langerhans. Compared with Tregs present in spleen and lymph node, Tregs in the islets showed evidence of antigen stimulation that correlated with higher proliferation and expression of activation markers CD103, ICOS, and TIGIT. T cell receptor (TCR) repertoire profiling demonstrated that islet Treg clonotypes are expanded in the islets, suggesting localized antigen-driven expansion in inflamed islets. To determine their specificity, we captured TCRαβ pairs from islet Tregs using single-cell TCR sequencing and found direct evidence that some of these TCRs were specific for islet-derived antigens including insulin B:9-23 and proinsulin. Consistently, insulin B:9-23 tetramers readily detected insulin-specific Tregs in the islets of NOD mice. Lastly, islet Tregs from prediabetic NOD mice were effective at preventing diabetes in Treg-deficient NOD.CD28-/- recipients. These results provide a glimpse into the specificities of Tregs in a natural repertoire that are crucial for opposing the progression of autoimmune diabetes.}, } @article {pmid29712851, year = {2018}, author = {DeRosha, DE and Holland, PL}, title = {Incorporating light atoms into synthetic analogues of FeMoco.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5054-5056}, pmid = {29712851}, issn = {1091-6490}, support = {R01 GM065313/GM/NIGMS NIH HHS/United States ; }, mesh = {*Molybdoferredoxin ; *Nitrogenase ; }, } @article {pmid29712850, year = {2018}, author = {Kim, KM and Wijerathne, T and Hur, JH and Kang, UJ and Kim, IH and Kweon, YC and Lee, AR and Jeong, SJ and Lee, SK and Lee, YY and Sim, BW and Lee, JH and Baig, C and Kim, SU and Chang, KT and Lee, KP and Park, CY}, title = {Distinct gating mechanism of SOC channel involving STIM-Orai coupling and an intramolecular interaction of Orai in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4623-E4632}, pmid = {29712850}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics/*metabolism ; Calcium/*metabolism ; Calcium Channels/chemistry/genetics/*metabolism ; Calcium Signaling ; Cell Membrane/metabolism ; Endoplasmic Reticulum/metabolism ; Evolution, Molecular ; HEK293 Cells ; Humans ; *Ion Channel Gating ; ORAI1 Protein/chemistry/genetics/*metabolism ; Sequence Homology ; Stromal Interaction Molecule 1/chemistry/genetics/*metabolism ; }, abstract = {Store-operated calcium entry (SOCE), an important mechanism of Ca2+ signaling in a wide range of cell types, is mediated by stromal interaction molecule (STIM), which senses the depletion of endoplasmic reticulum Ca2+ stores and binds and activates Orai channels in the plasma membrane. This inside-out mechanism of Ca2+ signaling raises an interesting question about the evolution of SOCE: How did these two proteins existing in different cellular compartments evolve to interact with each other? We investigated the gating mechanism of Caenorhabditis elegans Orai channels. Our analysis revealed a mechanism of Orai gating by STIM binding to the intracellular 2-3 loop of Orai in C. elegans that is radically different from Orai gating by STIM binding to the N and C termini of Orai in mammals. In addition, we found that the conserved hydrophobic amino acids in the 2-3 loop of Orai1 are important for the oligomerization and gating of channels and are regulated via an intramolecular interaction mechanism mediated by the N and C termini of Orai1. This study identifies a previously unknown SOCE mechanism in C. elegans and suggests that, while the STIM-Orai interaction is conserved between invertebrates and mammals, the gating mechanism for Orai channels differs considerably.}, } @article {pmid29712849, year = {2018}, author = {Liang, P and Stratil, TF and Popp, C and Marín, M and Folgmann, J and Mysore, KS and Wen, J and Ott, T}, title = {Symbiotic root infections in Medicago truncatula require remorin-mediated receptor stabilization in membrane nanodomains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5289-5294}, pmid = {29712849}, issn = {1091-6490}, mesh = {Carrier Proteins/genetics/*metabolism ; Cell Membrane/*metabolism ; Gene Expression Regulation, Plant ; Medicago truncatula/growth & development/metabolism/*microbiology ; Mutation ; Phosphoproteins/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified/growth & development/metabolism/*microbiology ; Receptors, Cell Surface/*chemistry/genetics/metabolism ; Rhizobium ; Root Nodules, Plant/growth & development/metabolism/*microbiology ; Sinorhizobium meliloti/*physiology ; *Symbiosis ; }, abstract = {Plant cell infection is tightly controlled by cell surface receptor-like kinases (RLKs). Like other RLKs, the Medicago truncatula entry receptor LYK3 laterally segregates into membrane nanodomains in a stimulus-dependent manner. Although nanodomain localization arises as a generic feature of plant membrane proteins, the molecular mechanisms underlying such dynamic transitions and their functional relevance have remained poorly understood. Here we demonstrate that actin and the flotillin protein FLOT4 form the primary and indispensable core of a specific nanodomain. Infection-dependent induction of the remorin protein and secondary molecular scaffold SYMREM1 results in subsequent recruitment of ligand-activated LYK3 and its stabilization within these membrane subcompartments. Reciprocally, the majority of this LYK3 receptor pool is destabilized at the plasma membrane and undergoes rapid endocytosis in symrem1 mutants on rhizobial inoculation, resulting in premature abortion of host cell infections. These data reveal that receptor recruitment into nanodomains is indispensable for their function during host cell infection.}, } @article {pmid29712848, year = {2018}, author = {Magida, JA and Evans, RM}, title = {Rational application of macrophage-specific LXR agonists avoids the pitfalls of SREBP-induced lipogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5051-5053}, pmid = {29712848}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Lipogenesis ; Liver ; Liver X Receptors ; Macrophages ; *Orphan Nuclear Receptors ; Receptors, Cytoplasmic and Nuclear ; }, } @article {pmid29712847, year = {2018}, author = {Parker, MJ and Maggiolo, AO and Thomas, WC and Kim, A and Meisburger, SP and Ando, N and Boal, AK and Stubbe, J}, title = {An endogenous dAMP ligand in Bacillus subtilis class Ib RNR promotes assembly of a noncanonical dimer for regulation by dATP.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4594-E4603}, pmid = {29712847}, issn = {1091-6490}, support = {R01 GM081393/GM/NIGMS NIH HHS/United States ; R00 GM100008/GM/NIGMS NIH HHS/United States ; R35 GM124847/GM/NIGMS NIH HHS/United States ; P41 GM103485/GM/NIGMS NIH HHS/United States ; S10 OD012289/OD/NIH HHS/United States ; F32 GM117757/GM/NIGMS NIH HHS/United States ; R35 GM119707/GM/NIGMS NIH HHS/United States ; K99 GM100008/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Allosteric Regulation ; Bacillus subtilis/*enzymology/genetics/growth & development ; Bacterial Proteins/chemistry/genetics/metabolism ; Deoxyadenine Nucleotides/chemistry/*metabolism ; Ligands ; Protein Binding ; Protein Conformation ; Ribonucleotide Reductases/*chemistry/genetics/*metabolism ; Scattering, Small Angle ; Substrate Specificity ; }, abstract = {The high fidelity of DNA replication and repair is attributable, in part, to the allosteric regulation of ribonucleotide reductases (RNRs) that maintains proper deoxynucleotide pool sizes and ratios in vivo. In class Ia RNRs, ATP (stimulatory) and dATP (inhibitory) regulate activity by binding to the ATP-cone domain at the N terminus of the large α subunit and altering the enzyme's quaternary structure. Class Ib RNRs, in contrast, have a partial cone domain and have generally been found to be insensitive to dATP inhibition. An exception is the Bacillus subtilis Ib RNR, which we recently reported to be inhibited by physiological concentrations of dATP. Here, we demonstrate that the α subunit of this RNR contains tightly bound deoxyadenosine 5'-monophosphate (dAMP) in its N-terminal domain and that dATP inhibition of CDP reduction is enhanced by its presence. X-ray crystallography reveals a previously unobserved (noncanonical) α2 dimer with its entire interface composed of the partial N-terminal cone domains, each binding a dAMP molecule. Using small-angle X-ray scattering (SAXS), we show that this noncanonical α2 dimer is the predominant form of the dAMP-bound α in solution and further show that addition of dATP leads to the formation of larger oligomers. Based on this information, we propose a model to describe the mechanism by which the noncanonical α2 inhibits the activity of the B. subtilis Ib RNR in a dATP- and dAMP-dependent manner.}, } @article {pmid29712846, year = {2018}, author = {Su, W and Kumar, V and Ding, Y and Ero, R and Serra, A and Lee, BST and Wong, ASW and Shi, J and Sze, SK and Yang, L and Gao, YG}, title = {Ribosome protection by antibiotic resistance ATP-binding cassette protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5157-5162}, pmid = {29712846}, issn = {1091-6490}, mesh = {ATP-Binding Cassette Transporters/chemistry/*metabolism ; Adenosine Triphosphate/metabolism ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects ; Bacterial Proteins/chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; *Drug Resistance, Microbial ; Models, Molecular ; Peptidyl Transferases/chemistry/metabolism ; Protein Biosynthesis ; Protein Conformation ; Ribosomes/chemistry/*drug effects/*metabolism ; }, abstract = {The ribosome is one of the richest targets for antibiotics. Unfortunately, antibiotic resistance is an urgent issue in clinical practice. Several ATP-binding cassette family proteins confer resistance to ribosome-targeting antibiotics through a yet unknown mechanism. Among them, MsrE has been implicated in macrolide resistance. Here, we report the cryo-EM structure of ATP form MsrE bound to the ribosome. Unlike previously characterized ribosomal protection proteins, MsrE is shown to bind to ribosomal exit site. Our structure reveals that the domain linker forms a unique needle-like arrangement with two crossed helices connected by an extended loop projecting into the peptidyl-transferase center and the nascent peptide exit tunnel, where numerous antibiotics bind. In combination with biochemical assays, our structure provides insight into how MsrE binding leads to conformational changes, which results in the release of the drug. This mechanism appears to be universal for the ABC-F type ribosome protection proteins.}, } @article {pmid29712845, year = {2018}, author = {Zhu, Q and High, FA and Zhang, C and Cerveira, E and Russell, MK and Longoni, M and Joy, MP and Ryan, M and Mil-Homens, A and Bellfy, L and Coletti, CM and Bhayani, P and Hila, R and Wilson, JM and Donahoe, PK and Lee, C}, title = {Systematic analysis of copy number variation associated with congenital diaphragmatic hernia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5247-5252}, pmid = {29712845}, issn = {1091-6490}, support = {P01 HD068250/HD/NICHD NIH HHS/United States ; T32 GM007748/GM/NIGMS NIH HHS/United States ; }, mesh = {Case-Control Studies ; Comparative Genomic Hybridization/*methods ; *DNA Copy Number Variations ; *Genetic Markers ; Hernias, Diaphragmatic, Congenital/*genetics ; Humans ; *Polymorphism, Single Nucleotide ; Prognosis ; }, abstract = {Congenital diaphragmatic hernia (CDH), characterized by malformation of the diaphragm and hypoplasia of the lungs, is one of the most common and severe birth defects, and is associated with high morbidity and mortality rates. There is growing evidence demonstrating that genetic factors contribute to CDH, although the pathogenesis remains largely elusive. Single-nucleotide polymorphisms have been studied in recent whole-exome sequencing efforts, but larger copy number variants (CNVs) have not yet been studied on a large scale in a case control study. To capture CNVs within CDH candidate regions, we developed and tested a targeted array comparative genomic hybridization platform to identify CNVs within 140 regions in 196 patients and 987 healthy controls, and identified six significant CNVs that were either unique to patients or enriched in patients compared with controls. These CDH-associated CNVs reveal high-priority candidate genes including HLX, LHX1, and HNF1B We also discuss CNVs that are present in only one patient in the cohort but have additional evidence of pathogenicity, including extremely rare large and/or de novo CNVs. The candidate genes within these predicted disease-causing CNVs form functional networks with other known CDH genes and play putative roles in DNA binding/transcription regulation and embryonic development. These data substantiate the importance of CNVs in the etiology of CDH, identify CDH candidate genes and pathways, and highlight the importance of ongoing analysis of CNVs in the study of CDH and other structural birth defects.}, } @article {pmid29712844, year = {2018}, author = {Behringer, MG and Choi, BI and Miller, SF and Doak, TG and Karty, JA and Guo, W and Lynch, M}, title = {Escherichia coli cultures maintain stable subpopulation structure during long-term evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4642-E4650}, pmid = {29712844}, issn = {1091-6490}, support = {F32 GM123703/GM/NIGMS NIH HHS/United States ; }, mesh = {Biofilms/growth & development ; Cells, Cultured ; Drug Resistance, Bacterial ; Escherichia coli/*genetics/growth & development ; Escherichia coli Infections/*microbiology ; Escherichia coli Proteins/genetics/*metabolism ; *Evolution, Molecular ; Fimbriae, Bacterial ; Food ; *Gene Expression Regulation, Bacterial ; *Genetic Variation ; Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Population Dynamics ; }, abstract = {How genetic variation is generated and maintained remains a central question in evolutionary biology. When presented with a complex environment, microbes can take advantage of genetic variation to exploit new niches. Here we present a massively parallel experiment where WT and repair-deficient (∆mutL) Escherichia coli populations have evolved over 3 y in a spatially heterogeneous and nutritionally complex environment. Metagenomic sequencing revealed that these initially isogenic populations evolved and maintained stable subpopulation structure in just 10 mL of medium for up to 10,000 generations, consisting of up to five major haplotypes with many minor haplotypes. We characterized the genomic, transcriptomic, exometabolomic, and phenotypic differences between clonal isolates, revealing subpopulation structure driven primarily by spatial segregation followed by differential utilization of nutrients. In addition to genes regulating the import and catabolism of nutrients, major polymorphisms of note included insertion elements transposing into fimE (regulator of the type I fimbriae) and upstream of hns (global regulator of environmental-change and stress-response genes), both known to regulate biofilm formation. Interestingly, these genes have also been identified as critical to colonization in uropathogenic E. coli infections. Our findings illustrate the complexity that can arise and persist even in small cultures, raising the possibility that infections may often be promoted by an evolving and complex pathogen population.}, } @article {pmid29712843, year = {2018}, author = {}, title = {Correction for Gao et al., Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4542}, doi = {10.1073/pnas.1806622115}, pmid = {29712843}, issn = {1091-6490}, } @article {pmid29712842, year = {2018}, author = {Böbel, TS and Hackl, SB and Langgartner, D and Jarczok, MN and Rohleder, N and Rook, GA and Lowry, CA and Gündel, H and Waller, C and Reber, SO}, title = {Less immune activation following social stress in rural vs. urban participants raised with regular or no animal contact, respectively.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5259-5264}, pmid = {29712842}, issn = {1091-6490}, mesh = {Adult ; Animals ; Cytokines/*blood ; Humans ; Hydrocortisone/blood ; Hypothalamo-Hypophyseal System/metabolism ; Immunity, Cellular/*immunology ; Leukocytes, Mononuclear/*immunology/metabolism ; Male ; *Pets ; Pituitary-Adrenal System/metabolism ; Rural Population/*statistics & numerical data ; Stress, Psychological/*physiopathology ; Urban Population/*statistics & numerical data ; Young Adult ; }, abstract = {Urbanization is on the rise, and environments offering a narrow range of microbial exposures are linked to an increased prevalence of both physical and mental disorders. Human and animal studies suggest that an overreactive immune system not only accompanies stress-associated disorders but might even be causally involved in their pathogenesis. Here, we show in young [mean age, years (SD): rural, 25.1 (0.78); urban, 24.5 (0.88)] healthy human volunteers that urban upbringing in the absence of pets (n = 20), relative to rural upbringing in the presence of farm animals (n = 20), was associated with a more pronounced increase in the number of peripheral blood mononuclear cells (PBMCs) and plasma interleukin 6 (IL-6) concentrations following acute psychosocial stress induced by the Trier social stress test (TSST). Moreover, ex vivo-cultured PBMCs from urban participants raised in the absence of animals secreted more IL-6 in response to the T cell-specific mitogen Con A. In turn, antiinflammatory IL-10 secretion was suppressed following TSST in urban participants raised in the absence of animals, suggesting immunoregulatory deficits, relative to rural participants raised in the presence of animals. Questionnaires, plasma cortisol, and salivary α-amylase, however, indicated the experimental protocol was more stressful and anxiogenic for rural participants raised in the presence of animals. Together, our findings support the hypothesis that urban vs. rural upbringing in the absence or presence of animals, respectively, increases vulnerability to stress-associated physical and mental disorders by compromising adequate resolution of systemic immune activation following social stress and, in turn, aggravating stress-associated systemic immune activation.}, } @article {pmid29712841, year = {2018}, author = {Zhu, F and Cusumano, A and Bloem, J and Weldegergis, BT and Villela, A and Fatouros, NE and van Loon, JJA and Dicke, M and Harvey, JA and Vogel, H and Poelman, EH}, title = {Symbiotic polydnavirus and venom reveal parasitoid to its hyperparasitoids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5205-5210}, pmid = {29712841}, issn = {1091-6490}, mesh = {Animals ; Butterflies/*parasitology/physiology/virology ; Ecosystem ; Gene Expression Regulation, Plant ; *Host-Parasite Interactions ; Larva/*parasitology/physiology/virology ; Plants/*metabolism/parasitology/virology ; Polydnaviridae/*physiology ; Symbiosis ; Venoms/*administration & dosage ; Wasps/*parasitology/physiology/virology ; }, abstract = {Symbiotic relationships may provide organisms with key innovations that aid in the establishment of new niches. For example, during oviposition, some species of parasitoid wasps, whose larvae develop inside the bodies of other insects, inject polydnaviruses into their hosts. These symbiotic viruses disrupt host immune responses, allowing the parasitoid's progeny to survive. Here we show that symbiotic polydnaviruses also have a downside to the parasitoid's progeny by initiating a multitrophic chain of interactions that reveals the parasitoid larvae to their enemies. These enemies are hyperparasitoids that use the parasitoid progeny as host for their own offspring. We found that the virus and venom injected by the parasitoid during oviposition, but not the parasitoid progeny itself, affected hyperparasitoid attraction toward plant volatiles induced by feeding of parasitized caterpillars. We identified activity of virus-related genes in the caterpillar salivary gland. Moreover, the virus affected the activity of elicitors of salivary origin that induce plant responses to caterpillar feeding. The changes in caterpillar saliva were critical in inducing plant volatiles that are used by hyperparasitoids to locate parasitized caterpillars. Our results show that symbiotic organisms may be key drivers of multitrophic ecological interactions. We anticipate that this phenomenon is widespread in nature, because of the abundance of symbiotic microorganisms across trophic levels in ecological communities. Their role should be more prominently integrated in community ecology to understand organization of natural and managed ecosystems, as well as adaptations of individual organisms that are part of these communities.}, } @article {pmid29712840, year = {2018}, author = {Mabuchi, K and Maki, H and Itaya, T and Suzuki, T and Nomoto, M and Sakaoka, S and Morikami, A and Higashiyama, T and Tada, Y and Busch, W and Tsukagoshi, H}, title = {MYB30 links ROS signaling, root cell elongation, and plant immune responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4710-E4719}, pmid = {29712840}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/growth & development/*immunology ; Arabidopsis Proteins/genetics/*metabolism ; *Gene Expression Regulation, Plant ; High-Throughput Nucleotide Sequencing ; Meristem/genetics/growth & development/*immunology ; Plant Immunity/*genetics ; Plant Roots/genetics/growth & development/*immunology ; Reactive Oxygen Species/*metabolism ; Signal Transduction ; Transcription Factors/genetics/*metabolism ; }, abstract = {Reactive oxygen species (ROS) are known to be important signal molecules that are involved in biotic and abiotic stress responses as well as in growth regulation. However, the molecular mechanisms by which ROS act as a growth regulator, as well as how ROS-dependent growth regulation relates to its roles in stress responses, are not well understood. We performed a time-course microarray analysis of Arabidopsis root tips upon treatment with hydrogen peroxide, which we named "ROS-map." Using the ROS-map, we identified an MYB transcription factor, MYB30, which showed a strong response to ROS treatment and is the key regulator of a gene network that leads to the hydrogen peroxide-dependent inhibition of root cell elongation. Intriguingly, this network contained multiple genes involved in very-long-chain fatty acid (VLCFA) transport. Finally, we showed that MYB30 is necessary for root growth regulation during defense responses, thus providing a molecular link between these two ROS-associated processes.}, } @article {pmid29712839, year = {2018}, author = {Gordon, TAC and Harding, HR and Wong, KE and Merchant, ND and Meekan, MG and McCormick, MI and Radford, AN and Simpson, SD}, title = {Habitat degradation negatively affects auditory settlement behavior of coral reef fishes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5193-5198}, pmid = {29712839}, issn = {1091-6490}, mesh = {*Acoustics ; Animals ; *Behavior, Animal ; Climate Change ; *Coral Reefs ; *Ecosystem ; Fishes/*physiology ; Larva ; *Sound ; }, abstract = {Coral reefs are increasingly degraded by climate-induced bleaching and storm damage. Reef recovery relies on recruitment of young fishes for the replenishment of functionally important taxa. Acoustic cues guide the orientation, habitat selection, and settlement of many fishes, but these processes may be impaired if degradation alters reef soundscapes. Here, we report spatiotemporally matched evidence of soundscapes altered by degradation from recordings taken before and after recent severe damage on Australia's Great Barrier Reef. Postdegradation soundscapes were an average of 15 dB re 1 µPa quieter and had significantly reduced acoustic complexity, richness, and rates of invertebrate snaps compared with their predegradation equivalents. We then used these matched recordings in complementary light-trap and patch-reef experiments to assess responses of wild fish larvae under natural conditions. We show that postdegradation soundscapes were 8% less attractive to presettlement larvae and resulted in 40% less settlement of juvenile fishes than predegradation soundscapes; postdegradation soundscapes were no more attractive than open-ocean sound. However, our experimental design does not allow an estimate of how much attraction and settlement to isolated postdegradation soundscapes might change compared with isolated predegradation soundscapes. Reductions in attraction and settlement were qualitatively similar across and within all trophic guilds and taxonomic groups analyzed. These patterns may lead to declines in fish populations, exacerbating degradation. Acoustic changes might therefore trigger a feedback loop that could impair reef resilience. To understand fully the recovery potential of coral reefs, we must learn to listen.}, } @article {pmid29712838, year = {2018}, author = {Daldrop, JO and Kappler, J and Brünig, FN and Netz, RR}, title = {Butane dihedral angle dynamics in water is dominated by internal friction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5169-5174}, pmid = {29712838}, issn = {1091-6490}, abstract = {The dihedral dynamics of butane in water is known to be rather insensitive to the water viscosity; possible explanations for this involve inertial effects or Kramers' turnover, the finite memory time of friction, and the presence of so-called internal friction. To disentangle these factors, we introduce a method to directly extract the friction memory function from unconstrained simulations in the presence of an arbitrary free-energy landscape. By analysis of the dihedral friction in butane for varying water viscosity, we demonstrate the existence of an internal friction contribution that does not scale linearly with water viscosity. At normal water viscosity, the internal friction turns out to be eight times larger than the solvent friction and thus completely dominates the effective friction. By comparison with simulations of a constrained butane molecule that has the dihedral as the only degree of freedom, we show that internal friction comes from the six additional degrees of freedom in unconstrained butane that are orthogonal to the dihedral angle reaction coordinate. While the insensitivity of butane's dihedral dynamics to water viscosity is solely due to the presence of internal friction, inertial effects nevertheless crucially influence the resultant transition rates. In contrast, non-Markovian effects due to the finite memory time are present but do not significantly influence the dihedral barrier-crossing rate of butane. These results not only settle the character of dihedral dynamics in small solvated molecular systems such as butane, they also have important implications for the folding of polymers and proteins.}, } @article {pmid29712837, year = {2018}, author = {Wang, J and Schultz, PG and Johnson, KA}, title = {Mechanistic studies of a small-molecule modulator of SMN2 splicing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4604-E4612}, pmid = {29712837}, issn = {1091-6490}, support = {R01 NS094721/NS/NINDS NIH HHS/United States ; }, mesh = {*Alternative Splicing ; DNA Helicases/chemistry/*genetics/metabolism ; DNA-Binding Proteins/chemistry/*genetics/metabolism ; Exons ; Humans ; Muscular Atrophy, Spinal/*genetics/metabolism/pathology ; Nucleic Acid Conformation ; Proteomics ; RNA Precursors/*genetics ; RNA-Binding Proteins/chemistry/*genetics/metabolism ; Small Molecule Libraries/*pharmacology ; Survival of Motor Neuron 2 Protein/chemistry/genetics/metabolism ; Trans-Activators/chemistry/*genetics/metabolism ; }, abstract = {RG-7916 is a first-in-class drug candidate for the treatment of spinal muscular atrophy (SMA) that functions by modulating pre-mRNA splicing of the SMN2 gene, resulting in a 2.5-fold increase in survival of motor neuron (SMN) protein level, a key protein lacking in SMA patients. RG-7916 is currently in three interventional phase 2 clinical trials for various types of SMA. In this report, we show that SMN-C2 and -C3, close analogs of RG-7916, act as selective RNA-binding ligands that modulate pre-mRNA splicing. Chemical proteomic and genomic techniques reveal that SMN-C2 directly binds to the AGGAAG motif on exon 7 of the SMN2 pre-mRNA, and promotes a conformational change in two to three unpaired nucleotides at the junction of intron 6 and exon 7 in both in vitro and in-cell models. This change creates a new functional binding surface that increases binding of the splicing modulators, far upstream element binding protein 1 (FUBP1) and its homolog, KH-type splicing regulatory protein (KHSRP), to the SMN-C2/C3-SMN2 pre-mRNA complex and enhances SMN2 splicing. These findings underscore the potential of small-molecule drugs to selectively bind RNA and modulate pre-mRNA splicing as an approach to the treatment of human disease.}, } @article {pmid29712836, year = {2018}, author = {Moqadam, M and Lervik, A and Riccardi, E and Venkatraman, V and Alsberg, BK and van Erp, TS}, title = {Local initiation conditions for water autoionization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4569-E4576}, pmid = {29712836}, issn = {1091-6490}, abstract = {The pH of liquid water is determined by the infrequent process in which water molecules split into short-lived hydroxide and hydronium ions. This reaction is difficult to probe experimentally and challenging to simulate. One of the open questions is whether the local water structure around a slightly stretched OH bond is actually initiating the eventual breakage of this bond or whether this event is driven by a global ordering that involves many water molecules far away from the reaction center. Here, we investigated the self-ionization of water at room temperature by rare-event ab initio molecular dynamics and obtained autoionization rates and activation energies in good agreement with experiments. Based on the analysis of thousands of molecular trajectories, we identified a couple of local order parameters and show that if a bond stretch occurs when all these parameters are around their ideal range, the chance for the first dissociation step (double-proton jump) increases from [Formula: see text] to 0.4. Understanding these initiation triggers might ultimately allow the steering of chemical reactions.}, } @article {pmid29712835, year = {2018}, author = {Fan, L and Zhang, F and Xu, S and Cui, X and Hussain, A and Fazli, L and Gleave, M and Dong, X and Qi, J}, title = {Histone demethylase JMJD1A promotes alternative splicing of AR variant 7 (AR-V7) in prostate cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4584-E4593}, pmid = {29712835}, issn = {1091-6490}, support = {I01 BX000545/BX/BLRD VA/United States ; R01 CA207118/CA/NCI NIH HHS/United States ; }, mesh = {*Alternative Splicing ; Animals ; Cell Proliferation ; Epigenesis, Genetic ; Exons ; *Gene Expression Regulation, Neoplastic ; Heterogeneous-Nuclear Ribonucleoprotein Group F-H/genetics/*metabolism ; Histones/genetics/metabolism ; Humans ; Jumonji Domain-Containing Histone Demethylases/genetics/*metabolism ; Male ; Mice, Inbred NOD ; Mice, SCID ; Prostatic Neoplasms/*genetics/metabolism/pathology ; RNA, Messenger ; Receptors, Androgen/*genetics ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Formation of the androgen receptor splicing variant 7 (AR-V7) is one of the major mechanisms by which resistance of prostate cancer to androgen deprivation therapy occurs. The histone demethylase JMJD1A (Jumonji domain containing 1A) functions as a key coactivator for AR by epigenetic regulation of H3K9 methylation marks. Here, we describe a role for JMJD1A in AR-V7 expression. While JMJD1A knockdown had no effect on full-length AR (AR-FL), it reduced AR-V7 levels in prostate cancer cells. Reexpression of AR-V7 in the JMJD1A-knockdown cells elevated expression of select AR targets and partially rescued prostate cancer cell growth in vitro and in vivo. The AR-V7 protein level correlated positively with JMJD1A in a subset of human prostate cancer specimens. Mechanistically, we found that JMJD1A promoted alternative splicing of AR-V7 through heterogeneous nuclear ribonucleoprotein F (HNRNPF), a splicing factor known to regulate exon inclusion. Knockdown of JMJD1A or HNRNPF inhibited splicing of AR-V7, but not AR-FL, in a minigene reporter assay. JMJD1A was found to interact with and promote the recruitment of HNRNPF to a cryptic exon 3b on AR pre-mRNA for the generation of AR-V7. Taken together, the role of JMJD1A in AR-FL coactivation and AR-V7 alternative splicing highlights JMJD1A as a potentially promising target for prostate cancer therapy.}, } @article {pmid29712834, year = {2018}, author = {Yanai, H and Chiba, S and Hangai, S and Kometani, K and Inoue, A and Kimura, Y and Abe, T and Kiyonari, H and Nishio, J and Taguchi-Atarashi, N and Mizushima, Y and Negishi, H and Grosschedl, R and Taniguchi, T}, title = {Revisiting the role of IRF3 in inflammation and immunity by conditional and specifically targeted gene ablation in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5253-5258}, pmid = {29712834}, issn = {1091-6490}, mesh = {Animals ; Gene Expression Regulation ; Immunity, Innate/*immunology ; Inflammation/chemically induced/genetics/*immunology/pathology ; Interferon Regulatory Factor-3/*metabolism ; Lipopolysaccharides/toxicity ; Mice ; Mice, Knockout ; Myeloid Cells/*immunology/metabolism/pathology ; Signal Transduction ; T-Lymphocytes/*immunology/metabolism/pathology ; }, abstract = {IFN regulatory factor 3 (IRF3) is a transcription regulator of cellular responses in many cell types that is known to be essential for innate immunity. To confirm IRF3's broad role in immunity and to more fully discern its role in various cellular subsets, we engineered Irf3-floxed mice to allow for the cell type-specific ablation of Irf3 Analysis of these mice confirmed the general requirement of IRF3 for the evocation of type I IFN responses in vitro and in vivo. Furthermore, immune cell ontogeny and frequencies of immune cell types were unaffected when Irf3 was selectively inactivated in either T cells or B cells in the mice. Interestingly, in a model of lipopolysaccharide-induced septic shock, selective Irf3 deficiency in myeloid cells led to reduced levels of type I IFN in the sera and increased survival of these mice, indicating the myeloid-specific, pathogenic role of the Toll-like receptor 4-IRF3 type I IFN axis in this model of sepsis. Thus, Irf3-floxed mice can serve as useful tool for further exploring the cell type-specific functions of this transcription factor.}, } @article {pmid29712833, year = {2018}, author = {Wang, X and Chen, ZH and Yang, C and Zhang, X and Jin, G and Chen, G and Wang, Y and Holford, P and Nevo, E and Zhang, G and Dai, F}, title = {Genomic adaptation to drought in wild barley is driven by edaphic natural selection at the Tabigha Evolution Slope.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5223-5228}, pmid = {29712833}, issn = {1091-6490}, mesh = {*Adaptation, Physiological ; Biological Evolution ; *Droughts ; *Gene Expression Regulation, Plant ; Genes, Plant ; Genomics/*methods ; Hordeum/*genetics ; Israel ; *Selection, Genetic ; }, abstract = {Ecological divergence at a microsite suggests adaptive evolution, and this study examined two abutting wild barley populations, each 100 m across, differentially adapted to drought tolerance on two contrasting soil types, Terra Rossa and basalt at the Tabigha Evolution Slope, Israel. We resequenced the genomes of seven and six wild barley genotypes inhabiting the Terra Rossa and basalt soils, respectively, and identified a total of 69,192,653 single-nucleotide variants (SNVs) and insertions/deletions in comparison with a reference barley genome. Comparative genomic analysis between these abutting wild barley populations involved 19,615,087 high-quality SNVs. The results revealed dramatically different selection sweep regions relevant to drought tolerance driven by edaphic natural selection within 2,577 selected genes in these regions, including key drought-responsive genes associated with ABA synthesis and degradation (such as Cytochrome P450 protein) and ABA receptor complex (such as PYL2, SNF1-related kinase). The genetic diversity of the wild barley population inhabiting Terra Rossa soil is much higher than that from the basalt soil. Additionally, we identified different sets of genes for drought adaptation in the wild barley populations from Terra Rossa soil and from wild barley populations from Evolution Canyon I at Mount Carmel. These genes are associated with abscisic acid signaling, signaling and metabolism of reactive oxygen species, detoxification and antioxidative systems, rapid osmotic adjustment, and deep root morphology. The unique mechanisms for drought adaptation of the wild barley from the Tabigha Evolution Slope may be useful for crop improvement, particularly for breeding of barley cultivars with high drought tolerance.}, } @article {pmid29712832, year = {2018}, author = {Lindenmayer, DB and Sato, C}, title = {Hidden collapse is driven by fire and logging in a socioecological forest ecosystem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5181-5186}, pmid = {29712832}, issn = {1091-6490}, mesh = {Australia ; *Biodiversity ; *Conservation of Natural Resources ; *Ecosystem ; *Fires ; *Forests ; Trees/*growth & development ; }, abstract = {Increasing numbers of ecosystems globally are at risk of collapse. However, most descriptions of terrestrial ecosystem collapse are post hoc with few empirically based examples of ecosystems in the process of collapse. This limits learning about collapse and impedes development of effective early-warning indicators. Based on multidecadal and multifaceted monitoring, we present evidence that the Australian mainland Mountain Ash ecosystem is collapsing. Collapse is indicated by marked changes in ecosystem condition, particularly the rapid decline in populations of keystone ecosystem structures. There also has been significant decline in biodiversity strongly associated with these structures and disruptions of key ecosystem processes. In documenting the decline of the Mountain Ash ecosystem, we uncovered evidence of hidden collapse. This is where an ecosystem superficially appears to be relatively intact, but a prolonged period of decline coupled with long lag times for recovery of dominant ecosystem components mean that collapse is almost inevitable. In ecosystems susceptible to hidden collapse, management interventions will be required decades earlier than currently perceived by policy makers. Responding to hidden collapse is further complicated by our finding that different drivers produce different pathways to collapse, but these drivers can interact in ways that exacerbate and perpetuate collapse. Management must focus not only on reducing the number of critical stressors influencing an ecosystem but also on breaking feedbacks between stressors. We demonstrate the importance of multidecadal monitoring programs in measuring state variables that can inform quantitative predictions of collapse as well as help identify management responses that can avert system-wide collapse.}, } @article {pmid29712831, year = {2018}, author = {Moldakarimov, S and Bazhenov, M and Feldman, DE and Sejnowski, TJ}, title = {Structured networks support sparse traveling waves in rodent somatosensory cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5277-5282}, pmid = {29712831}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Action Potentials ; Animals ; Electric Stimulation ; *Neural Networks (Computer) ; Neural Pathways/*physiology ; Neurons/*physiology ; Rodentia ; Somatosensory Cortex/*physiology ; Vibrissae/*physiology ; }, abstract = {Neurons responding to different whiskers are spatially intermixed in the superficial layer 2/3 (L2/3) of the rodent barrel cortex, where a single whisker deflection activates a sparse, distributed neuronal population that spans multiple cortical columns. How the superficial layer of the rodent barrel cortex is organized to support such distributed sensory representations is not clear. In a computer model, we tested the hypothesis that sensory representations in L2/3 of the rodent barrel cortex are formed by activity propagation horizontally within L2/3 from a site of initial activation. The model explained the observed properties of L2/3 neurons, including the low average response probability in the majority of responding L2/3 neurons, and the existence of a small subset of reliably responding L2/3 neurons. Sparsely propagating traveling waves similar to those observed in L2/3 of the rodent barrel cortex occurred in the model only when a subnetwork of strongly connected neurons was immersed in a much larger network of weakly connected neurons.}, } @article {pmid29712830, year = {2018}, author = {Pourmousa, M and Song, HD and He, Y and Heinecke, JW and Segrest, JP and Pastor, RW}, title = {Tertiary structure of apolipoprotein A-I in nascent high-density lipoproteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5163-5168}, pmid = {29712830}, issn = {1091-6490}, support = {P01 HL092969/HL/NHLBI NIH HHS/United States ; P01 HL128203/HL/NHLBI NIH HHS/United States ; P30 DK017047/DK/NIDDK NIH HHS/United States ; R01 GM116961/GM/NIGMS NIH HHS/United States ; }, mesh = {Apolipoprotein A-I/*chemistry/metabolism ; Cholesterol/*chemistry/metabolism ; Humans ; Lipoproteins, HDL/*chemistry/metabolism ; Molecular Dynamics Simulation ; Phospholipids/*chemistry/metabolism ; Protein Structure, Tertiary ; }, abstract = {Understanding the function of high-density lipoprotein (HDL) requires detailed knowledge of the structure of its primary protein, apolipoprotein A-I (APOA1). However, APOA1 flexibility and HDL heterogeneity have confounded decades of efforts to determine high-resolution structures and consistent models. Here, molecular dynamics simulations totaling 30 μs on two nascent HDLs, each with 2 APOA1 and either 160 phospholipids and 24 cholesterols or 200 phospholipids and 20 cholesterols, show that residues 1-21 of the N-terminal domains of APOA1 interact via strong salt bridges. Residues 26-43 of one APOA1 in the smaller particle form a hinge on the disc edge, which displaces the C-terminal domain of the other APOA1 to the phospholipid surface. The proposed structures are supported by chemical cross-linking, Rosetta modeling of the N-terminal domain, and analysis of the lipid-free ∆185APOA1 crystal structure. These structures provide a framework for understanding HDL maturation and revise all previous models of nascent HDL.}, } @article {pmid29712829, year = {2018}, author = {}, title = {Correction for Sheehan et al., Coevolution of landesque capital intensive agriculture and sociopolitical hierarchy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4541}, doi = {10.1073/pnas.1806254115}, pmid = {29712829}, issn = {1091-6490}, } @article {pmid29712828, year = {2018}, author = {Brown, M and Korte, M and Holme, R and Wardinski, I and Gunnarson, S}, title = {Earth's magnetic field is probably not reversing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5111-5116}, pmid = {29712828}, issn = {1091-6490}, abstract = {The geomagnetic field has been decaying at a rate of ∼5% per century from at least 1840, with indirect observations suggesting a decay since 1600 or even earlier. This has led to the assertion that the geomagnetic field may be undergoing a reversal or an excursion. We have derived a model of the geomagnetic field spanning 30-50 ka, constructed to study the behavior of the two most recent excursions: the Laschamp and Mono Lake, centered at 41 and 34 ka, respectively. Here, we show that neither excursion demonstrates field evolution similar to current changes in the geomagnetic field. At earlier times, centered at 49 and 46 ka, the field is comparable to today's field, with an intensity structure similar to today's South Atlantic Anomaly (SAA); however, neither of these SAA-like fields develop into an excursion or reversal. This suggests that the current weakened field will also recover without an extreme event such as an excursion or reversal. The SAA-like field structure at 46 ka appears to be coeval with published increases in geomagnetically modulated beryllium and chlorine nuclide production, despite the global dipole field not weakening significantly in our model during this time. This agreement suggests a greater complexity in the relationship between cosmogenic nuclide production and the geomagnetic field than is commonly assumed.}, } @article {pmid29712827, year = {2018}, author = {Baym, G}, title = {Retrospective of Charles Pence Slichter (NAS 1967).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {5624-5625}, pmid = {29712827}, issn = {1091-6490}, } @article {pmid29712826, year = {2018}, author = {Deng, W and Wang, Y and Zhang, S and Gupta, KM and Hülsey, MJ and Asakura, H and Liu, L and Han, Y and Karp, EM and Beckham, GT and Dyson, PJ and Jiang, J and Tanaka, T and Wang, Y and Yan, N}, title = {Catalytic amino acid production from biomass-derived intermediates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5093-5098}, pmid = {29712826}, issn = {1091-6490}, mesh = {Amino Acids/chemistry/*metabolism ; *Biomass ; Catalysis ; Hydrogenation ; Nanoparticles/*chemistry ; Nanotubes, Carbon/*chemistry ; Nickel/chemistry ; Ruthenium/chemistry ; }, abstract = {Amino acids are the building blocks for protein biosynthesis and find use in myriad industrial applications including in food for humans, in animal feed, and as precursors for bio-based plastics, among others. However, the development of efficient chemical methods to convert abundant and renewable feedstocks into amino acids has been largely unsuccessful to date. To that end, here we report a heterogeneous catalyst that directly transforms lignocellulosic biomass-derived α-hydroxyl acids into α-amino acids, including alanine, leucine, valine, aspartic acid, and phenylalanine in high yields. The reaction follows a dehydrogenation-reductive amination pathway, with dehydrogenation as the rate-determining step. Ruthenium nanoparticles supported on carbon nanotubes (Ru/CNT) exhibit exceptional efficiency compared with catalysts based on other metals, due to the unique, reversible enhancement effect of NH3 on Ru in dehydrogenation. Based on the catalytic system, a two-step chemical process was designed to convert glucose into alanine in 43% yield, comparable with the well-established microbial cultivation process, and therefore, the present strategy enables a route for the production of amino acids from renewable feedstocks. Moreover, a conceptual process design employing membrane distillation to facilitate product purification is proposed and validated. Overall, this study offers a rapid and potentially more efficient chemical method to produce amino acids from woody biomass components.}, } @article {pmid29712825, year = {2018}, author = {Roke, D and Wezenberg, SJ and Feringa, BL}, title = {Molecular rotary motors: Unidirectional motion around double bonds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9423-9431}, pmid = {29712825}, issn = {1091-6490}, abstract = {The field of synthetic molecular machines has quickly evolved in recent years, growing from a fundamental curiosity to a highly active field of chemistry. Many different applications are being explored in areas such as catalysis, self-assembled and nanostructured materials, and molecular electronics. Rotary molecular motors hold great promise for achieving dynamic control of molecular functions as well as for powering nanoscale devices. However, for these motors to reach their full potential, many challenges still need to be addressed. In this paper we focus on the design principles of rotary motors featuring a double-bond axle and discuss the major challenges that are ahead of us. Although great progress has been made, further design improvements, for example in terms of efficiency, energy input, and environmental adaptability, will be crucial to fully exploit the opportunities that these rotary motors offer.}, } @article {pmid29712824, year = {2018}, author = {Dutta, S and Eckmann, JP and Libchaber, A and Tlusty, T}, title = {Green function of correlated genes in a minimal mechanical model of protein evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4559-E4568}, pmid = {29712824}, issn = {1091-6490}, mesh = {Computational Biology/*methods ; *Epistasis, Genetic ; *Evolution, Molecular ; Humans ; *Mutation ; Phenotype ; Proteins/*chemistry/genetics/metabolism ; }, abstract = {The function of proteins arises from cooperative interactions and rearrangements of their amino acids, which exhibit large-scale dynamical modes. Long-range correlations have also been revealed in protein sequences, and this has motivated the search for physical links between the observed genetic and dynamic cooperativity. We outline here a simplified theory of protein, which relates sequence correlations to physical interactions and to the emergence of mechanical function. Our protein is modeled as a strongly coupled amino acid network with interactions and motions that are captured by the mechanical propagator, the Green function. The propagator describes how the gene determines the connectivity of the amino acids and thereby, the transmission of forces. Mutations introduce localized perturbations to the propagator that scatter the force field. The emergence of function is manifested by a topological transition when a band of such perturbations divides the protein into subdomains. We find that epistasis-the interaction among mutations in the gene-is related to the nonlinearity of the Green function, which can be interpreted as a sum over multiple scattering paths. We apply this mechanical framework to simulations of protein evolution and observe long-range epistasis, which facilitates collective functional modes.}, } @article {pmid29712823, year = {2018}, author = {Froehlich, HE and Runge, CA and Gentry, RR and Gaines, SD and Halpern, BS}, title = {Comparative terrestrial feed and land use of an aquaculture-dominant world.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5295-5300}, pmid = {29712823}, issn = {1091-6490}, mesh = {Animal Feed/*analysis ; Animals ; *Aquaculture ; Conservation of Natural Resources ; *Crops, Agricultural ; *Diet ; Farms/*statistics & numerical data ; *Food Supply ; *Global Health ; Humans ; Seafood ; }, abstract = {Reducing food production pressures on the environment while feeding an ever-growing human population is one of the grand challenges facing humanity. The magnitude of environmental impacts from food production, largely around land use, has motivated evaluation of the environmental and health benefits of shifting diets, typically away from meat toward other sources, including seafood. However, total global catch of wild seafood has remained relatively unchanged for the last two decades, suggesting increased demand for seafood will mostly have to rely on aquaculture (i.e., aquatic farming). Increasingly, cultivated aquatic species depend on feed inputs from agricultural sources, raising concerns around further straining crops and land use for feed. However, the relative impact and potential of aquaculture remains unclear. Here we simulate how different forms of aquaculture contribute and compare with feed and land use of terrestrial meat production and how spatial patterns might change by midcentury if diets move toward more cultured seafood and less meat. Using country-level aquatic and terrestrial data, we show that aquaculture requires less feed crops and land, even if over one-third of protein production comes from aquaculture by 2050. However, feed and land-sparing benefits are spatially heterogeneous, driven by differing patterns of production, trade, and feed composition. Ultimately, our study highlights the future potential and uncertainties of considering aquaculture in the portfolio of sustainability solutions around one of the largest anthropogenic impacts on the planet.}, } @article {pmid29712822, year = {2018}, author = {Jiang, Z and McDonald, BC and Worden, H and Worden, JR and Miyazaki, K and Qu, Z and Henze, DK and Jones, DBA and Arellano, AF and Fischer, EV and Zhu, L and Boersma, KF}, title = {Unexpected slowdown of US pollutant emission reduction in the past decade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5099-5104}, pmid = {29712822}, issn = {1091-6490}, mesh = {Air Pollutants/*analysis ; Air Pollution/*analysis ; Carbon Monoxide/*analysis ; Environmental Monitoring/*standards ; Gasoline ; Humans ; Nitrogen Oxides/*analysis ; Particulate Matter/*analysis ; United States ; Vehicle Emissions/*analysis ; }, abstract = {Ground and satellite observations show that air pollution regulations in the United States (US) have resulted in substantial reductions in emissions and corresponding improvements in air quality over the last several decades. However, large uncertainties remain in evaluating how recent regulations affect different emission sectors and pollutant trends. Here we show a significant slowdown in decreasing US emissions of nitrogen oxides (NO x) and carbon monoxide (CO) for 2011-2015 using satellite and surface measurements. This observed slowdown in emission reductions is significantly different from the trend expected using US Environmental Protection Agency (EPA) bottom-up inventories and impedes compliance with local and federal agency air-quality goals. We find that the difference between observations and EPA's NO x emission estimates could be explained by: (i) growing relative contributions of industrial, area, and off-road sources, (ii) decreasing relative contributions of on-road gasoline, and (iii) slower than expected decreases in on-road diesel emissions.}, } @article {pmid29712573, year = {2018}, author = {Riani, YD and Matsuda, T and Takemoto, K and Nagai, T}, title = {Green monomeric photosensitizing fluorescent protein for photo-inducible protein inactivation and cell ablation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {50}, pmid = {29712573}, issn = {1741-7007}, abstract = {BACKGROUND: Photosensitizing fluorescent proteins, which generate reactive oxygen species (ROS) upon light irradiation, are useful for spatiotemporal protein inactivation and cell ablation. They give us clues about protein function, intracellular signaling pathways and intercellular interactions. Since ROS generation of a photosensitizer is specifically controlled by certain excitation wavelengths, utilizing colour variants of photosensitizing protein would allow multi-spatiotemporal control of inactivation. To expand the colour palette of photosensitizing protein, here we developed SuperNova Green from its red predecessor, SuperNova.

RESULTS: SuperNova Green is able to produce ROS spatiotemporally upon blue light irradiation. Based on protein characterization, SuperNova Green produces insignificant amounts of singlet oxygen and predominantly produces superoxide and its derivatives. We utilized SuperNova Green to specifically inactivate the pleckstrin homology domain of phospholipase C-δ1 and to ablate cancer cells in vitro. As a proof of concept for multi-spatiotemporal control of inactivation, we demonstrate that SuperNova Green can be used with its red variant, SuperNova, to perform independent protein inactivation or cell ablation studies in a spatiotemporal manner by selective light irradiation.

CONCLUSION: Development of SuperNova Green has expanded the photosensitizing protein toolbox to optogenetically control protein inactivation and cell ablation.}, } @article {pmid29712565, year = {2018}, author = {Fan, W and Zhao, M and Li, S and Bai, X and Li, J and Meng, H and Mu, Z}, title = {Correction to: Contrasting transcriptional responses of PYR1/PYL/RCAR ABA receptors to ABA or dehydration stress between maize seedling leaves and roots.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {73}, pmid = {29712565}, issn = {1471-2229}, abstract = {Following publication of the original article [1], a reader spotted that the article appears to have some misplaced/duplicated figures. In particular, Fig. 5a and Fig. 6a appear to be identical, and do not match what is written in the text. The authors apologized for this oversight and supplied the original pictures, which are reproduced below.}, } @article {pmid29709692, year = {2018}, author = {Steiner, FM and Csősz, S and Markó, B and Gamisch, A and Rinnhofer, L and Folterbauer, C and Hammerle, S and Stauffer, C and Arthofer, W and Schlick-Steiner, BC}, title = {Turning one into five: Integrative taxonomy uncovers complex evolution of cryptic species in the harvester ant Messor "structor".}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {387-404}, doi = {10.1016/j.ympev.2018.04.005}, pmid = {29709692}, issn = {1095-9513}, abstract = {Seed harvesting ants are ecosystem engineers that shape vegetation, nutrient cycles, and microclimate. Progress in ecological research is, however, slowed down by poor species delimitation. For example, it has not been resolved to date, how many species the European harvester ant Messor "structor" (Latreille, 1798) represents. Since its first description, splitting into additional taxa was often proposed but not accepted later on due to inconsistent support from morphology and ecology. Here, we took an iterative integrative-taxonomy approach - comparing multiple, independent data sets of the same sample - and used traditional morphometrics, Wolbachia symbionts, mitochondrial DNA, amplified fragment length polymorphism, and ecological niche modelling. Using the complementarity of the data sets applied, we resolved multiple, strong disagreements over the number of species, ranging from four to ten, and the allocation of individuals to species. We consider most plausible a five-species hypothesis and conclude the taxonomic odyssey by redescribing Messor structor, M. ibericus Santschi, 1925, and M. muticus (Nylander, 1849) stat.rev., and by describing two new species, M. ponticus sp.n. and M. mcarthuri sp.n. The evolutionary explanations invoked in resolving the various data conflicts include pronounced morphological crypsis, incomplete lineage-sorting or ongoing cospeciation of endosymbionts, and peripatric speciation - these ants' significance to evolutionary biology parallels that to ecology. The successful solution of this particular problem illustrates the usefulness of the integrative approach to other systematic problems of comparable complexity and the importance of understanding evolution to drawing correct conclusions on species' attributes, including their ecology and biogeography.}, } @article {pmid29709691, year = {2018}, author = {Sassone, AB and Giussani, LM}, title = {Reconstructing the phylogenetic history of the tribe Leucocoryneae (Allioideae): Reticulate evolution and diversification in South America.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {437-448}, doi = {10.1016/j.ympev.2018.04.034}, pmid = {29709691}, issn = {1095-9513}, abstract = {At present, the Allioideae is included within the Amaryllidaceae, which is an economically important bulb crop subfamily that includes onion, garlic, and ornamental species worldwide. The Allioideae includes four tribes geographically disjunct namely: Allieae, widespread in the northern hemisphere, tribe Tulbaghieae distributed in South Africa, and tribes Leucocoryneae and Gilliesieae are endemic to South America. Although we agree with the current tribal circumscription of the Leucocoryneae including Beauverdia, Ipheion, Latace, Leucocoryne, Nothoscordum, and Tristagma, there are still taxonomic and phylogenetic uncertainties regarding the monophyly, phylogenetic relationships, and divergence time of several lineages in a biogeographic context. In this study, a comprehensive molecular phylogeny of the tribe Leucocoryneae was inferred based on nuclear ribosomal ITS and plastid (ndhF and matK) sequences. We used Bayesian inference and maximum parsimony analyses to predict ancestor-descendant relationships. Our results confirmed the monophyly of the four tribes of subfamily Allioideae. Similarly, within the Leucocoryneae, Ipheion, Leucocoryne, and Nothosocordum Sect. Inodorum were also monophyletic; Tristagma and Nothoscordum would be monophyletic if including Ipheion and Beauverdia, respectively. Network analyses were implemented to reveal putative scenarios of reticulate evolution. Both, current and ancestral hybridization events have presumably occurred among species of Nothoscordum Sect. Nothoscordum and Beauverdia favored by spatial overlapping of populations, flowering synchrony and a puzzling pattern of cytogenetic attributes. The estimation of divergence time indicates that the tribe Leucocoryneae originated in the Late Oligocene in southern South America with possible ancestors in Africa. Most crown lineages within the tribe diversified in conjunction with biogeographical events during the Late Miocene to Pliocene. We posit that new suitable environments available after the Andean uplift and during the Age of the Southern Plains provided the favorable geographic setting for the major lineages of Leucocoryneae in southern Pampas, extra-Andean Patagonia, Andean mountains, and in Chile. Hybridization, polyploidization, and Robertsonian translocations of chromosomes have been the driving forces and major sources of speciation in the evolution of tribe Leucocoryneae.}, } @article {pmid29709601, year = {2018}, author = {Womble, M and Amin, NM and Nascone-Yoder, N}, title = {The left-right asymmetry of liver lobation is generated by Pitx2c-mediated asymmetries in the hepatic diverticulum.}, journal = {Developmental biology}, volume = {439}, number = {2}, pages = {80-91}, pmid = {29709601}, issn = {1095-564X}, support = {R01 DK085300/DK/NIDDK NIH HHS/United States ; R21 OD017963/OD/NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/genetics ; Diverticulum/embryology/metabolism ; Embryo, Nonmammalian/metabolism ; Gene Expression Regulation, Developmental/genetics ; Homeodomain Proteins/*metabolism/physiology ; Liver/*embryology/physiology ; Morphogenesis/physiology ; Transcription Factors/metabolism ; Xenopus/*embryology/physiology ; Xenopus Proteins/*metabolism/physiology ; }, abstract = {Internal organs exhibit left-right asymmetric sizes, shapes and anatomical positions, but how these different lateralities develop is poorly understood. Here we use the experimentally tractable Xenopus model to uncover the morphogenetic events that drive the left-right asymmetrical lobation of the liver. On the right side of the early hepatic diverticulum, endoderm cells become columnar and apically constricted, forming an expanded epithelial surface and, ultimately, an enlarged right liver lobe. In contrast, the cells on the left side become rounder, and rearrange into a compact, stratified architecture that produces a smaller left lobe. Side-specific gain- and loss-of-function studies reveal that asymmetric expression of the left-right determinant Pitx2c elicits distinct epithelial morphogenesis events in the left side of the diverticulum. Surprisingly, the cellular events induced by Pitx2c during liver development are opposite those induced in other digestive organs, suggesting divergent cellular mechanisms underlie the formation of different lateralities.}, } @article {pmid29709600, year = {2018}, author = {Kadokura, S and Sugimoto, K and Tarr, P and Suzuki, T and Matsunaga, S}, title = {Characterization of somatic embryogenesis initiated from the Arabidopsis shoot apex.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {13-27}, doi = {10.1016/j.ydbio.2018.04.023}, pmid = {29709600}, issn = {1095-564X}, mesh = {Arabidopsis/embryology/*genetics ; Arabidopsis Proteins/genetics ; Cellular Reprogramming/*genetics ; Gene Expression Regulation, Plant/*genetics ; Meristem/metabolism ; Plant Leaves/metabolism ; Plant Shoots/metabolism ; Plant Somatic Embryogenesis Techniques/methods ; Transcriptome ; }, abstract = {Somatic embryogenesis is one of the best examples of the remarkable developmental plasticity of plants, in which committed somatic cells can dedifferentiate and acquire the ability to form an embryo and regenerate an entire plant. In Arabidopsis thaliana, the shoot apices of young seedlings have been reported as an alternative tissue source for somatic embryos (SEs) besides the widely studied zygotic embryos taken from siliques. Although SE induction from shoots demonstrates the plasticity of plants more clearly than the embryo-to-embryo induction system, the underlying developmental and molecular mechanisms involved are unknown. Here we characterized SE formation from shoot apex explants by establishing a system for time-lapse observation of explants during SE induction. We also established a method to distinguish SE-forming and non-SE-forming explants prior to anatomical SE formation, enabling us to identify distinct transcriptome profiles of these two explants at SE initiation. We show that embryonic fate commitment takes place at day 3 of SE induction and the SE arises directly, not through callus formation, from the base of leaf primordia just beside the shoot apical meristem (SAM), where auxin accumulates and shoot-root polarity is formed. The expression domain of a couple of key developmental genes for the SAM transiently expands at this stage. Our data demonstrate that SE-forming and non-SE-forming explants share mostly the same transcripts except for a limited number of embryonic genes and root genes that might trigger the SE-initiation program. Thus, SE-forming explants possess a mixed identity (SAM, root and embryo) at the time of SE specification.}, } @article {pmid29709599, year = {2018}, author = {Palmisano, NJ and Meléndez, A}, title = {Autophagy in C. elegans development.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29709599}, issn = {1095-564X}, support = {R15 GM102846/GM/NIGMS NIH HHS/United States ; }, abstract = {Autophagy involves the sequestration of cytoplasmic contents in a double-membrane structure referred to as the autophagosome and the degradation of its contents upon delivery to lysosomes. Autophagy activity has a role in multiple biological processes during the development of the nematode Caenorhabditis elegans. Basal levels of autophagy are required to remove aggregate prone proteins, paternal mitochondria, and spermatid-specific membranous organelles. During larval development, autophagy is required for the remodeling that occurs during dauer development, and autophagy can selectively degrade components of the miRNA-induced silencing complex, and modulate miRNA-mediated silencing. Basal levels of autophagy are important in synapse formation and in the germ line, to promote the proliferation of proliferating stem cells. Autophagy activity is also required for the efficient removal of apoptotic cell corpses by promoting phagosome maturation. Finally, autophagy is also involved in lipid homeostasis and in the aging process. In this review, we first describe the molecular complexes involved in the process of autophagy, its regulation, and mechanisms for cargo recognition. In the second section, we discuss the developmental contexts where autophagy has been shown to be important. Studies in C. elegans provide valuable insights into the physiological relevance of this process during metazoan development.}, } @article {pmid29709598, year = {2018}, author = {Monteiro, RS and Gentsch, GE and Smith, JC}, title = {Transcriptomics of dorso-ventral axis determination in Xenopus tropicalis.}, journal = {Developmental biology}, volume = {439}, number = {2}, pages = {69-79}, pmid = {29709598}, issn = {1095-564X}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Body Patterning/*genetics ; Gastrula/embryology/metabolism ; Gastrulation/*genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental/genetics ; Germ Layers/metabolism ; Lithium Chloride/adverse effects ; Signal Transduction/physiology ; Transcriptome/genetics ; Ultraviolet Rays/adverse effects ; Wnt Proteins/metabolism ; Xenopus/*embryology/genetics ; Xenopus Proteins/genetics/metabolism ; }, abstract = {Amphibian embryos provide a powerful system to study early cell fate determination because their eggs are externally fertilised, large, and easy to manipulate. Ultraviolet (UV) or lithium chloride (LiCl) treatment are classic embryonic manipulations frequently used to perturb specification of the dorso-ventral (DV) axis by affecting the stability of the maternal Wnt mediator β-catenin. Such treatments result in the formation of so-called ventralised or dorsalised embryos. Although these phenotypes have been well described with respect to their morphology and some aspects of gene expression, their whole transcriptomes have never been systematically characterised and compared. Here we show that at the early gastrula stage UV-treated embryos are transcriptionally more closely related to untreated embryos than to LiCl-treated embryos. Transcriptional comparisons with dissected ventral and dorsal regions of unperturbed gastrula embryos indicate that UV and LiCl treatments indeed enrich for ventral and dorsal cells, respectively. However, these treatments also affect the balance of neural induction in the ectodermal germ layer, with LiCl stimulating pro-neural BMP inhibition and UV preferentially generating epidermis because of elevated BMP levels. Thus the transcriptomes of UV- and LiCl-treated embryos can best be described as ventro-epidermalised and dorso-neuralised. These descriptions notwithstanding, our profiling reveals several hitherto uncharacterized genes with differential expression along the DV axis. At least one of these genes, a RNF220-like ubiquitin ligase, is activated dorsally by β-catenin. Our analysis of UV/LiCl-mediated axis perturbation will enhance the mechanistic understanding of DV axis determination in vertebrates.}, } @article {pmid29709597, year = {2018}, author = {Blin, M and Tine, E and Meister, L and Elipot, Y and Bibliowicz, J and Espinasa, L and Rétaux, S}, title = {Developmental evolution and developmental plasticity of the olfactory epithelium and olfactory skills in Mexican cavefish.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {242-251}, doi = {10.1016/j.ydbio.2018.04.019}, pmid = {29709597}, issn = {1095-564X}, mesh = {Animals ; Behavior, Animal/*physiology ; Cell Death/physiology ; Cell Proliferation/physiology ; Characiformes/*embryology ; Neural Stem Cells/cytology/*metabolism ; Olfactory Mucosa/cytology/*embryology ; Olfactory Perception/*physiology ; Smell/*physiology ; }, abstract = {The fish Astyanax mexicanus comes in two forms: the normal surface-dwelling (SF) and the blind depigmented cave-adapted (CF) morphs. Among many phenotypic differences, cavefish show enhanced olfactory sensitivity to detect amino-acid odors and they possess large olfactory sensory organs. Here, we questioned the relationship between the size of the olfactory organ and olfactory capacities. Comparing olfactory detection abilities of CF, SF and F1 hybrids with various olfactory epithelium (OE) sizes in behavioral tests, we concluded that OE size is not the only factor involved. Other possibilities were envisaged. First, olfactory behavior was tested in SF raised in the dark or after embryonic lens ablation, which leads to eye degeneration and mimics the CF condition. Both absence of visual function and absence of visual organs improved the SF olfactory detection capacities, without affecting the size of their OE. This suggested that developmental plasticity occurs between the visual and the olfactory modalities, and can be recruited in SF after visual deprivation. Second, the development of the olfactory epithelium was compared in SF and CF in their first month of life. Proliferation, cell death, neuronal lifespan, and olfactory progenitor cell cycling properties were identical in the two morphs. By contrast, the proportions of the three main olfactory sensory neurons subtypes (ciliated, microvillous and crypt) in their OE differed. OMP-positive ciliated neurons were more represented in SF, TRPC2-positive microvillous neurons were proportionately more abundant in CF, and S100-positive crypt cells were found in equal densities in the two morphs. Thus, general proliferative properties of olfactory progenitors are identical but neurogenic properties differ and lead to variations in the neuronal composition of the OE in SF and CF. Together, these experiments suggest that there are at least two components in the evolution of cavefish olfactory skills: (1) one part of eye-dependent developmental phenotypic plasticity, which does not depend on the size of the olfactory organ, and (2) one part of developmental evolution of the OE, which may stem from embryonic specification of olfactory neurons progenitor pools.}, } @article {pmid29709293, year = {2018}, author = {Terhune, CE and Ritzman, TB and Robinson, CA}, title = {Mandibular ramus shape variation and ontogeny in Homo sapiens and Homo neanderthalensis.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {55-71}, doi = {10.1016/j.jhevol.2018.03.009}, pmid = {29709293}, issn = {1095-8606}, abstract = {As the interface between the mandible and cranium, the mandibular ramus is functionally significant and its morphology has been suggested to be informative for taxonomic and phylogenetic analyses. In primates, and particularly in great apes and humans, ramus morphology is highly variable, especially in the shape of the coronoid process and the relationship of the ramus to the alveolar margin. Here we compare ramus shape variation through ontogeny in Homo neanderthalensis to that of modern and fossil Homo sapiens using geometric morphometric analyses of two-dimensional semilandmarks and univariate measurements of ramus angulation and relative coronoid and condyle height. Results suggest that ramus, especially coronoid, morphology varies within and among subadult and adult modern human populations, with the Alaskan Inuit being particularly distinct. We also identify significant differences in overall anterosuperior ramus and coronoid shapes between H. sapiens and H. neanderthalensis, both in adults and throughout ontogeny. These shape differences are subtle, however, and we therefore suggest caution when using ramus morphology to diagnose group membership for individual specimens of these taxa. Furthermore, we argue that these morphologies are unlikely to be representative of differences in masticatory biomechanics and/or paramasticatory behaviors between Neanderthals and modern humans, as has been suggested by previous authors. Assessments of ontogenetic patterns of shape change reveal that the typical Neanderthal ramus morphology is established early in ontogeny, and there is little evidence for divergent postnatal ontogenetic allometric trajectories between Neanderthals and modern humans as a whole. This analysis informs our understanding of intraspecific patterns of mandibular shape variation and ontogeny in H. sapiens and can shed further light on overall developmental and life history differences between H. sapiens and H. neanderthalensis.}, } @article {pmid29709292, year = {2018}, author = {Guatelli-Steinberg, D and O'Hara, MC and Le Cabec, A and Delezene, LK and Reid, DJ and Skinner, MM and Berger, LR}, title = {Patterns of lateral enamel growth in Homo naledi as assessed through perikymata distribution and number.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {40-54}, doi = {10.1016/j.jhevol.2018.03.007}, pmid = {29709292}, issn = {1095-8606}, abstract = {Perikymata, incremental growth lines visible on tooth enamel surfaces, differ in their distribution and number among hominin species, although with overlapping patterns. This study asks: (1) How does the distribution of perikymata along the lateral enamel surface of Homo naledi anterior teeth compare to that of other hominins? (2) When both perikymata distribution and number are analyzed together, how distinct is H. naledi from other hominins? A total of 19 permanent anterior teeth (incisors and canines) of H. naledi were compared, by tooth type, to permanent anterior teeth of other hominins: Australopithecus afarensis, Australopithecus africanus, Paranthropus robustus, Paranthropus boisei, Homo ergaster/Homo erectus, other early Homo, Neandertals, and modern humans, with varying sample sizes. Repeated measures analyses of the percentage of perikymata per decile of reconstructed crown height yielded several statistically significant differences between H. naledi and other hominins. Canonical variates analysis of percentage of perikymata in the cervical half of the crown together with perikymata number revealed that, in 8 of 19 cases, H. naledi teeth were significantly unlikely to be classified as other hominins, while exhibiting least difference from modern humans (especially southern Africans). In a cross-validated analysis, 68% of the H. naledi teeth were classified as such, while 32% were classified as modern human (most often southern African). Of 313 comparative teeth use for this analysis, only 1.9% were classified as H. naledi. What tends to differentiate H. naledi anterior tooth crowns from those of most other hominins, including some modern humans, is strongly skewed perikymata distributions combined with perikymata numbers that fall in the middle to lower ranges of hominin values. H. naledi therefore tends toward a particular combination of these features that is less often seen in other hominins. Implications of these data for the growth and development of H. naledi anterior teeth are considered.}, } @article {pmid29709204, year = {2018}, author = {Skoglund, P and Mathieson, I}, title = {Ancient Genomics of Modern Humans: The First Decade.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {381-404}, doi = {10.1146/annurev-genom-083117-021749}, pmid = {29709204}, issn = {1545-293X}, abstract = {The first decade of ancient genomics has revolutionized the study of human prehistory and evolution. We review new insights based on prehistoric modern human genomes, including greatly increased resolution of the timing and structure of the out-of-Africa expansion, the diversification of present-day non-African populations, and the earliest expansions of those populations into Eurasia and America. Prehistoric genomes now document population transformations on every inhabited continent-in particular the effect of agricultural expansions in Africa, Europe, and Oceania-and record a history of natural selection that shapes present-day phenotypic diversity. Despite these advances, much remains unknown, in particular about the genomic histories of Asia (the most populous continent) and Africa (the continent that contains the most genetic diversity). Ancient genomes from these and other regions, integrated with a growing understanding of the genomic basis of human phenotypic diversity, will be in focus during the next decade of research in the field.}, } @article {pmid29709203, year = {2018}, author = {O'Neal, WK and Knowles, MR}, title = {Cystic Fibrosis Disease Modifiers: Complex Genetics Defines the Phenotypic Diversity in a Monogenic Disease.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {201-222}, doi = {10.1146/annurev-genom-083117-021329}, pmid = {29709203}, issn = {1545-293X}, abstract = {In many respects, genetic studies in cystic fibrosis (CF) serve as a paradigm for a human Mendelian genetic success story. From recognition of the condition as a heritable pathological entity to implementation of personalized treatments based on genetic findings, this multistep pathway of progress has focused on the genetic underpinnings of CF clinical disease. Along this path was the recognition that not all CFTR gene mutations produce the same disease and the recognition of the complex, multifactorial nature of CF genotype-phenotype relationships. The non- CFTR genetic components (gene modifiers) that contribute to variation in phenotype are the focus of this review. A multifaceted approach involving candidate gene studies, genome-wide association studies, and gene expression studies has revealed significant gene modifiers for multiple CF phenotypes. The bold challenges for the future are to integrate the findings into our understanding of CF pathogenesis and to use the knowledge to develop novel therapies.}, } @article {pmid29709202, year = {2018}, author = {Burgess, S and Foley, CN and Zuber, V}, title = {Inferring Causal Relationships Between Risk Factors and Outcomes from Genome-Wide Association Study Data.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {303-327}, doi = {10.1146/annurev-genom-083117-021731}, pmid = {29709202}, issn = {1545-293X}, abstract = {An observational correlation between a suspected risk factor and an outcome does not necessarily imply that interventions on levels of the risk factor will have a causal impact on the outcome (correlation is not causation). If genetic variants associated with the risk factor are also associated with the outcome, then this increases the plausibility that the risk factor is a causal determinant of the outcome. However, if the genetic variants in the analysis do not have a specific biological link to the risk factor, then causal claims can be spurious. We review the Mendelian randomization paradigm for making causal inferences using genetic variants. We consider monogenic analysis, in which genetic variants are taken from a single gene region, and polygenic analysis, which includes variants from multiple regions. We focus on answering two questions: When can Mendelian randomization be used to make reliable causal inferences, and when can it be used to make relevant causal inferences?}, } @article {pmid29709200, year = {2018}, author = {Cappellini, E and Prohaska, A and Racimo, F and Welker, F and Pedersen, MW and Allentoft, ME and de Barros Damgaard, P and Gutenbrunner, P and Dunne, J and Hammann, S and Roffet-Salque, M and Ilardo, M and Moreno-Mayar, JV and Wang, Y and Sikora, M and Vinner, L and Cox, J and Evershed, RP and Willerslev, E}, title = {Ancient Biomolecules and Evolutionary Inference.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {1029-1060}, doi = {10.1146/annurev-biochem-062917-012002}, pmid = {29709200}, issn = {1545-4509}, abstract = {Over the past three decades, studies of ancient biomolecules-particularly ancient DNA, proteins, and lipids-have revolutionized our understanding of evolutionary history. Though initially fraught with many challenges, today the field stands on firm foundations. Researchers now successfully retrieve nucleotide and amino acid sequences, as well as lipid signatures, from progressively older samples, originating from geographic areas and depositional environments that, until recently, were regarded as hostile to long-term preservation of biomolecules. Sampling frequencies and the spatial and temporal scope of studies have also increased markedly, and with them the size and quality of the data sets generated. This progress has been made possible by continuous technical innovations in analytical methods, enhanced criteria for the selection of ancient samples, integrated experimental methods, and advanced computational approaches. Here, we discuss the history and current state of ancient biomolecule research, its applications to evolutionary inference, and future directions for this young and exciting field.}, } @article {pmid29709199, year = {2018}, author = {Syed, A and Tainer, JA}, title = {The MRE11-RAD50-NBS1 Complex Conducts the Orchestration of Damage Signaling and Outcomes to Stress in DNA Replication and Repair.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {263-294}, pmid = {29709199}, issn = {1545-4509}, support = {P01 CA092584/CA/NCI NIH HHS/United States ; R01 CA117638/CA/NCI NIH HHS/United States ; R01 CA200231/CA/NCI NIH HHS/United States ; }, abstract = {Genomic instability in disease and its fidelity in health depend on the DNA damage response (DDR), regulated in part from the complex of meiotic recombination 11 homolog 1 (MRE11), ATP-binding cassette-ATPase (RAD50), and phosphopeptide-binding Nijmegen breakage syndrome protein 1 (NBS1). The MRE11-RAD50-NBS1 (MRN) complex forms a multifunctional DDR machine. Within its network assemblies, MRN is the core conductor for the initial and sustained responses to DNA double-strand breaks, stalled replication forks, dysfunctional telomeres, and viral DNA infection. MRN can interfere with cancer therapy and is an attractive target for precision medicine. Its conformations change the paradigm whereby kinases initiate damage sensing. Delineated results reveal kinase activation, posttranslational targeting, functional scaffolding, conformations storing binding energy and enabling access, interactions with hub proteins such as replication protein A (RPA), and distinct networks at DNA breaks and forks. MRN biochemistry provides prototypic insights into how it initiates, implements, and regulates multifunctional responses to genomic stress.}, } @article {pmid29708647, year = {2018}, author = {Izquierdo-Bueno, I and González-Rodríguez, VE and Simon, A and Dalmais, B and Pradier, JM and Le Pêcheur, P and Mercier, A and Walker, AS and Garrido, C and Collado, IG and Viaud, M}, title = {Biosynthesis of abscisic acid in fungi: identification of a sesquiterpene cyclase as the key enzyme in Botrytis cinerea.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2469-2482}, doi = {10.1111/1462-2920.14258}, pmid = {29708647}, issn = {1462-2920}, abstract = {While abscisic acid (ABA) is known as a hormone produced by plants through the carotenoid pathway, a small number of phytopathogenic fungi are also able to produce this sesquiterpene but they use a distinct pathway that starts with the cyclization of farnesyl diphosphate (FPP) into 2Z,4E-α-ionylideneethane which is then subjected to several oxidation steps. To identify the sesquiterpene cyclase (STC) responsible for the biosynthesis of ABA in fungi, we conducted a genomic approach in Botrytis cinerea. The genome of the ABA-overproducing strain ATCC58025 was fully sequenced and five STC-coding genes were identified. Among them, Bcstc5 exhibits an expression profile concomitant with ABA production. Gene inactivation, complementation and chemical analysis demonstrated that BcStc5/BcAba5 is the key enzyme responsible for the key step of ABA biosynthesis in fungi. Unlike what is observed for most of the fungal secondary metabolism genes, the key enzyme-coding gene Bcstc5/Bcaba5 is not clustered with the other biosynthetic genes, i.e., Bcaba1 to Bcaba4 that are responsible for the oxidative transformation of 2Z,4E-α-ionylideneethane. Finally, our study revealed that the presence of the Bcaba genes among Botrytis species is rare and that the majority of them do not possess the ability to produce ABA.}, } @article {pmid29708646, year = {2018}, author = {Fixen, KR and Pal Chowdhury, N and Martinez-Perez, M and Poudel, S and Boyd, ES and Harwood, CS}, title = {The path of electron transfer to nitrogenase in a phototrophic alpha-proteobacterium.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2500-2508}, doi = {10.1111/1462-2920.14262}, pmid = {29708646}, issn = {1462-2920}, abstract = {The phototrophic alpha-proteobacterium, Rhodopseudomonas palustris, is a model for studies of regulatory and physiological parameters that control the activity of nitrogenase. This enzyme produces the energy-rich compound H2 , in addition to converting N2 gas to NH3 . Nitrogenase is an ATP-requiring enzyme that uses large amounts of reducing power, but the electron transfer pathway to nitrogenase in R. palustris was incompletely known. Here, we show that the ferredoxin, Fer1, is the primary but not sole electron carrier protein encoded by R. palustris that serves as an electron donor to nitrogenase. A flavodoxin, FldA, is also an important electron donor, especially under iron limitation. We present a model where the electron bifurcating complex, FixABCX, can reduce both ferredoxin and flavodoxin to transfer electrons to nitrogenase, and we present bioinformatic evidence that FixABCX and Fer1 form a conserved electron transfer pathway to nitrogenase in nitrogen-fixing proteobacteria. These results may be useful in the design of strategies to reroute electrons generated during metabolism of organic compounds to nitrogenase to achieve maximal activity.}, } @article {pmid29708645, year = {2018}, author = {Herren, CM and McMahon, KD}, title = {Keystone taxa predict compositional change in microbial communities.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14257}, pmid = {29708645}, issn = {1462-2920}, abstract = {The influence of biotic interactions on microbial community assembly is intensely debated. We hypothesized that keystone taxa, which influence community assembly through strong biotic interactions, are important for regulating microbial community composition. While highly connected microbes have been identified, evidence that these taxa act as keystones is lacking, because keystone status requires influence on whole-community dynamics. We address this gap, showing that small subsets of highly connected keystone taxa (generally 1%-5% of richness) can be optimal predictors of whole-community compositional change. In three long-term data sets, greater connectivity due to the presence of keystone taxa corresponded to lower compositional turnover. We further hypothesized that the influence of keystone taxa would be diminished when environmental disturbance was a strong driver of compositional change. We used two case studies of reference and disturbed communities to investigate how biotic and abiotic forces interact to shape community composition. Most of the same taxa were present in both the reference and disturbed communities, but keystone taxa had much greater explanatory power in the reference communities. Our results suggest that greater biotic connectivity arising from the presence of keystone taxa is stabilizing to community composition, and that keystone taxa can be good indicators of pending community shifts.}, } @article {pmid29708644, year = {2018}, author = {Sánchez-Hevia, DL and Yuste, L and Moreno, R and Rojo, F}, title = {Influence of the Hfq and Crc global regulators on the control of iron homeostasis in Pseudomonas putida.}, journal = {Environmental microbiology}, volume = {20}, number = {10}, pages = {3484-3503}, doi = {10.1111/1462-2920.14263}, pmid = {29708644}, issn = {1462-2920}, abstract = {Metabolically versatile bacteria use catabolite repression control to select their preferred carbon sources, thus optimizing carbon metabolism. In pseudomonads, this occurs through the combined action of the proteins Hfq and Crc, which form stable tripartite complexes at target mRNAs, inhibiting their translation. The activity of Hfq/Crc is antagonised by small RNAs of the CrcZ family, the amounts of which vary according to carbon availability. The present work examines the role of Pseudomonas putida Hfq protein under conditions of low-level catabolite repression, in which Crc protein would have a minor role since it is sequestered by CrcZ/CrcY. The results suggest that, under these conditions, Hfq remains operative and plays an important role in iron homeostasis. In this scenario, Crc appears to participate indirectly by helping CrcZ/CrcY to control the amount of free Hfq in the cell. Iron homeostasis in pseudomonads relies on regulatory elements such as the Fur protein, the PrrF1-F2 sRNAs, and several extracytoplasmic sigma factors. Our results show that the absence of Hfq is paralleled by a reduction in PrrF1-F2 small RNAs. Hfq thus provides a regulatory link between iron and carbon metabolism, coordinating the iron supply to meet the needs of the enzymes operational under particular nutritional regimes.}, } @article {pmid29708639, year = {2018}, author = {Otte, JM and Harter, J and Laufer, K and Blackwell, N and Straub, D and Kappler, A and Kleindienst, S}, title = {The distribution of active iron-cycling bacteria in marine and freshwater sediments is decoupled from geochemical gradients.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2483-2499}, doi = {10.1111/1462-2920.14260}, pmid = {29708639}, issn = {1462-2920}, abstract = {Microaerophilic, phototrophic and nitrate-reducing Fe(II)-oxidizers co-exist in coastal marine and littoral freshwater sediments. However, the in situ abundance, distribution and diversity of metabolically active Fe(II)-oxidizers remained largely unexplored. Here, we characterized the microbial community composition at the oxic-anoxic interface of littoral freshwater (Lake Constance, Germany) and coastal marine sediments (Kalø Vig and Norsminde Fjord, Denmark) using DNA-/RNA-based next-generation 16S rRNA (gene) amplicon sequencing. All three physiological groups of neutrophilic Fe(II)-oxidizing bacteria were found to be active in marine and freshwater sediments, revealing up to 0.2% anoxygenic photoferrotrophs (e.g., Rhodopseudomonas, Rhodobacter, Chlorobium), 0.1% microaerophilic Fe(II)-oxidizers (e.g., Mariprofundus, Hyphomonas, Gallionella) and 0.3% nitrate-reducing Fe(II)-oxidizers (e.g., Thiobacillus, Pseudomonas, Denitromonas, Hoeflea). Active Fe(III)-reducing bacteria (e.g., Shewanella, Geobacter) were most abundant (up to 2.8%) in marine sediments and co-occurred with cable bacteria (up to 4.5%). Geochemical profiles of Fe(III), Fe(II), O2 , light, nitrate and total organic carbon revealed a redox stratification of the sediments and explained 75%-85% of the vertical distribution of microbial taxa, while active Fe-cycling bacteria were found to be decoupled from geochemical gradients. We suggest that metabolic flexibility, microniches in the sediments, or interrelationships with cable bacteria might explain the distribution patterns of active Fe-cycling bacteria.}, } @article {pmid29708635, year = {2018}, author = {Hu, SK and Liu, Z and Alexander, H and Campbell, V and Connell, PE and Dyhrman, ST and Heidelberg, KB and Caron, DA}, title = {Shifting metabolic priorities among key protistan taxa within and below the euphotic zone.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2865-2879}, doi = {10.1111/1462-2920.14259}, pmid = {29708635}, issn = {1462-2920}, support = {3299//Gordon and Betty Moore Foundation/ ; 1136818//National Science Foundation/ ; }, abstract = {A metatranscriptome study targeting the protistan community was conducted off the coast of Southern California, at the San Pedro Ocean Time-series station at the surface, 150 m (oxycline), and 890 m to link putative metabolic patterns to distinct protistan lineages. Comparison of relative transcript abundances revealed depth-related shifts in the nutritional modes of key taxonomic groups. Eukaryotic gene expression in the sunlit surface environment was dominated by phototrophs, such as diatoms and chlorophytes, and high abundances of transcripts associated with synthesis pathways (e.g., photosynthesis, carbon fixation, fatty acid synthesis). Sub-euphotic depths (150 and 890 m) exhibited strong contributions from dinoflagellates and ciliates, and were characterized by transcripts relating to digestion or intracellular nutrient recycling (e.g., breakdown of fatty acids and V-type ATPases). These transcriptional patterns underlie the distinct nutritional modes of ecologically important protistan lineages that drive marine food webs, and provide a framework to investigate trophic dynamics across diverse protistan communities.}, } @article {pmid29707906, year = {2018}, author = {Díez-Vives, C and Esteves, AIS and Costa, R and Nielsen, S and Thomas, T}, title = {Detecting signatures of a sponge-associated lifestyle in bacterial genomes.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {433-443}, doi = {10.1111/1758-2229.12655}, pmid = {29707906}, issn = {1758-2229}, abstract = {Sponges interact with diverse and rich communities of bacteria that are phylogenetically often distinct from their free-living counterparts. Recent genomics and metagenomic studies have indicated that bacterial sponge symbionts also have distinct functional features from free-living bacteria; however, it is unclear, if such genome-derived functional signatures are common and present in different symbiont taxa. We therefore compared here a large set of genomes from cultured (Pseudovibrio, Ruegeria and Aquimarina) and yet-uncultivated (Synechococcus) bacteria found in either sponge-associated or free-living sources. Our analysis revealed only very few genera-specific functions that could be correlated with a sponge-associated lifestyle. Using different sets of sponge-associated and free-living bacteria for each genus, we could however show that the functions identified as 'sponge-associated' are dependent on the reference comparison being made. Using simulation approaches, we show how this influences the robustness of identifying functional signatures and how evolutionary divergence and genomic adaptation can be distinguished. Our results highlight the future need for robust comparative analyses to define genomic signatures of symbiotic lifestyles, whether it is for symbionts of sponges or other host organisms.}, } @article {pmid29706232, year = {2018}, author = {de la Torre, I and Mora, R}, title = {Technological behaviour in the early Acheulean of EF-HR (Olduvai Gorge, Tanzania).}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {329-377}, doi = {10.1016/j.jhevol.2018.01.003}, pmid = {29706232}, issn = {1095-8606}, abstract = {Technological strategies of early humans are discussed in the light of a recently excavated stone tool assemblage from EF-HR, an archaeological site older than 1.33 Ma at Olduvai Gorge, Tanzania. Renewed fieldwork at EF-HR has unearthed a lithic collection containing over 2300 artefacts (including a hundred handaxes in stratigraphic position), which represents one of the largest assemblages for the early Acheulean in eastern Africa. Our technological study shows co-occurrence of two distinctive reduction sequences in the same assemblage, one aimed at obtaining small flakes and the other focused on the production of large, thick, heavy flakes that were then used as blanks for handaxe shaping. Flaking of small cores is expedient and low intensity, and knapping methods are similar to those observed in earlier Oldowan assemblages. Large Cutting Tools (LCTs) show no evidence of planform and biconvex symmetry, and shaping sequences are brief and discontinuous, indicating short use-lives for handaxes. Bifaces are rare and atypical. Recurrent morphotypes are knives, which are poorly-shaped, scraper-like, large-sized handaxes. Despite the apparent expediency of EF-HR handaxe production, a closer inspection of the interplay between debitage and façonnage stages reveals remarkably standardized procedural patterns. Large Cutting Tool blanks were produced following fixed knapping rules resulting in flakes with a specific morphology and mass distribution. Adapted to the idiosyncrasies of each blank, shaping was almost invariably imposed over the same areas in all LCTs and sought to produce morphotypes that, technologically, are remarkably identical to each other. This strongly supports the existence of mental templates and technical rules that were systematically practiced in LCT production at EF-HR, and underscore the structured nature of technological behaviour at the onset of the Acheulean in eastern Africa.}, } @article {pmid29706231, year = {2018}, author = {Neubauer, S and Gunz, P and Leakey, L and Leakey, M and Hublin, JJ and Spoor, F}, title = {Reconstruction, endocranial form and taxonomic affinity of the early Homo calvaria KNM-ER 42700.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {25-39}, doi = {10.1016/j.jhevol.2018.04.005}, pmid = {29706231}, issn = {1095-8606}, abstract = {When first described, the small calvaria KNM-ER 42700 from Ileret, Kenya, was considered a late juvenile or young adult and assigned to Homo erectus. However, this species attribution has subsequently been challenged because the specimen's neurocranial shape differs substantially from that of H. erectus adults. Here, (1) we describe the postmortem damage and deformation that could have influenced previous shape analyses, (2) present digital reconstructions based on computed tomographic scans correcting for these taphonomic defects, and (3) analyze the reconstructed endocranial shape and form, considering both static allometry among adults and ontogenetic allometry. To this end, we use geometric morphometrics to analyze the shape of digital endocasts based on landmarks and semilandmarks. Corroborating previous studies of the external surface, we find that the endocranial shape of KNM-ER 42700 falls outside the known adult variation of H. erectus. With an endocranial volume estimate between 721 and 744 ml, size cannot explain its atypical endocranial shape when static allometry within H. erectus is considered. However, the analysis of ontogenetic allometry suggests that it may be a H. erectus individual that is younger than previously thought and had not yet reached adult endocranial shape. Future work should therefore comprehensively review all cranial indicators of its developmental age, including closure of the spheno-occipital synchondrosis. An alternative hypothesis is that KNM-ER 42700 represents an as yet unidentified species of early Homo. Importantly, KNM-ER 42700 should not be included in the adult hypodigm of H. erectus.}, } @article {pmid29706230, year = {2018}, author = {Ryan, TM and Carlson, KJ and Gordon, AD and Jablonski, N and Shaw, CN and Stock, JT}, title = {Human-like hip joint loading in Australopithecus africanus and Paranthropus robustus.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {12-24}, doi = {10.1016/j.jhevol.2018.03.008}, pmid = {29706230}, issn = {1095-8606}, abstract = {Adaptations indicative of habitual bipedalism are present in the earliest recognized hominins. However, debate persists about various aspects of bipedal locomotor behavior in fossil hominins, including the nature of gait kinematics, locomotor variability across different species, and the degree to which various australopith species engaged in arboreal behaviors. In this study, we analyze variation in trabecular bone structure of the femoral head using a sample of modern humans, extant non-human hominoids, baboons, and fossil hominins attributed to Australopithecus africanus, Paranthropus robustus, and the genus Homo. We use μCT data to characterize the fabric anisotropy, material orientation, and bone volume fraction of trabecular bone to reconstruct hip joint loading conditions in these fossil hominins. Femoral head trabecular bone fabric structure in australopiths is more similar to that of modern humans and Pleistocene Homo than extant apes, indicating that these australopith individuals walked with human-like hip kinematics, including a more limited range of habitual hip joint postures (e.g., a more extended hip) during bipedalism. Our results also indicate that australopiths have robust femoral head trabecular bone, suggesting overall increased loading of the musculoskeletal system comparable to that imposed by extant apes. These results provide new evidence of human-like bipedal locomotion in Pliocene hominins, even while other aspects of their musculoskeletal systems retain ape-like characteristics.}, } @article {pmid29706229, year = {2018}, author = {Daver, G and Berillon, G and Jacquier, C and Ardagna, Y and Yadeta, M and Maurin, T and Souron, A and Blondel, C and Coppens, Y and Boisserie, JR}, title = {New hominin postcranial remains from locality OMO 323, Shungura Formation, Lower Omo Valley, southwestern Ethiopia.}, journal = {Journal of human evolution}, volume = {122}, number = {}, pages = {23-32}, doi = {10.1016/j.jhevol.2018.03.011}, pmid = {29706229}, issn = {1095-8606}, } @article {pmid29706137, year = {2018}, author = {Wei, G and Liu, K and Shen, T and Shi, J and Liu, B and Han, M and Peng, M and Fu, H and Song, Y and Zhu, J and Dong, A and Ni, T}, title = {Position-specific intron retention is mediated by the histone methyltransferase SDG725.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {44}, pmid = {29706137}, issn = {1741-7007}, abstract = {BACKGROUND: Intron retention (IR), the most prevalent alternative splicing form in plants, plays a critical role in gene expression during plant development and stress response. However, the molecular mechanisms underlying IR regulation remain largely unknown.

RESULTS: Knockdown of SDG725, a histone H3 lysine 36 (H3K36)-specific methyltransferase in rice, leads to alterations of IR in more than 4700 genes. Surprisingly, IR events are globally increased at the 5' region but decreased at the 3' region of the gene body in the SDG725-knockdown mutant. Chromatin immunoprecipitation sequencing analyses reveal that SDG725 depletion results in a genome-wide increase of the H3K36 mono-methylation (H3K36me1) but, unexpectedly, promoter-proximal shifts of H3K36 di- and tri-methylation (H3K36me2 and H3K36me3). Consistent with the results in animals, the levels of H3K36me1/me2/me3 in rice positively correlate with gene expression levels, whereas shifts of H3K36me2/me3 coincide with position-specific alterations of IR. We find that either H3K36me2 or H3K36me3 alone contributes to the positional change of IR caused by SDG725 knockdown, although IR shift is more significant when both H3K36me2 and H3K36me3 modifications are simultaneously shifted.

CONCLUSIONS: Our results revealed that SDG725 modulates IR in a position-specific manner, indicating that H3K36 methylation plays a role in RNA splicing, probably by marking the retained introns in plants.}, } @article {pmid29705890, year = {2018}, author = {Shu, W and Yu, Y and Chen, S and Yan, X and Liu, Y and Zhao, Y}, title = {Selective Formation of Ser-His Dipeptide via Phosphorus Activation.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {2}, pages = {213-222}, pmid = {29705890}, issn = {1573-0875}, support = {No. 21232005, No. 21375113//the Chinese National Science Foundation/ ; No. 20720150049//the Fundamental Research Funds for the Central Universities/ ; }, mesh = {Catalysis ; Dipeptides/*chemical synthesis ; Evolution, Chemical ; Hydrolases/chemistry ; *Origin of Life ; Phosphorus/*chemistry ; }, abstract = {The Ser-His dipeptide is the shortest active peptide. This dipeptide not only hydrolyzes proteins and DNA but also catalyzes the formation of peptides and phosphodiester bonds. As a potential candidate for the prototype of modern hydrolase, Ser-His has attracted increasing attention. To explore if Ser-His could be obtained efficiently in the prebiotic condition, we investigated the reactions of N-DIPP-Ser with His or other amino acids in an aqueous system. We observed that N-DIPP-Ser incubated with His can form Ser-His more efficiently than with other amino acids. A synergistic effect involving the two side chains of Ser and His is presumed to be the critical factor for the selectivity of this specific peptide formation.}, } @article {pmid29705632, year = {2018}, author = {Jones, D and Elf, J}, title = {Bursting onto the scene? Exploring stochastic mRNA production in bacteria.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {124-130}, doi = {10.1016/j.mib.2018.04.001}, pmid = {29705632}, issn = {1879-0364}, abstract = {Recent large-scale measurements of gene expression variability (or noise) in E. coli have led to the unexpected conclusion that the variability is in large part dictated by and increasing with the mean level of expression. Here we review the evidence for this apparent universal trend in variability, as well as for the related idea that transcription is fundamentally bursty. We examine recently proposed mechanisms for burstiness and universality and argue that they do not explain important features of observed data. Finally, we discuss potential limitations and pitfalls in the interpretation of experimental measurements of cell-to-cell variability.}, } @article {pmid29705582, year = {2018}, author = {Kasl, EL and Font, WF and Criscione, CD}, title = {Resolving evolutionary changes in parasite life cycle complexity: Molecular phylogeny of the trematode genus Alloglossidium indicates more than one origin of precociousness.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {371-381}, doi = {10.1016/j.ympev.2018.04.027}, pmid = {29705582}, issn = {1095-9513}, mesh = {Animals ; Catfishes/parasitology ; DNA, Mitochondrial/genetics ; Haplotypes/genetics ; *Life Cycle Stages ; Parasites/*growth & development ; *Phylogeny ; Trematoda/*growth & development ; }, abstract = {The evolutionary causes and consequences of changes in complex life cycles are of central importance in parasitology. However, data remain limited because in part, knowledge on phylogenetic relationships among species that differ in life cycle patterns remains scarce. We present a molecular phylogeny of the trematode genus Alloglossidium, which contains several species that display precocious (a.k.a., progenetic) life cycles (i.e., maturation in what is typically regarded as an intermediate host). The molecular phylogeny contrasts with previous morphological and life-history based phylogenetic hypotheses. In particular, a precocious life cycle wherein leeches are used as final hosts evolved early in the history of the genus. Among the remaining species, which are a separate clade, a three-host life cycle using ictalurid catfishes is ancestral. Furthermore, there are at least two additional independent evolutionary events that lead to a precocious life cycle where a catfish host is lost and a crustacean is used as a final host. We conclude with a discussion on how existing hypotheses on the evolution of precociousness, and parasite life cycle complexity in general, may or may not relate to the patterns observed in genus Alloglossidium.}, } @article {pmid29705579, year = {2018}, author = {Fairlamb, AH and Horn, D}, title = {Melarsoprol Resistance in African Trypanosomiasis.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {481-492}, doi = {10.1016/j.pt.2018.04.002}, pmid = {29705579}, issn = {1471-5007}, support = {MR/K000500/1//Medical Research Council/United Kingdom ; 203134/Z/16/Z//Wellcome Trust/United Kingdom ; 100320/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Aquaglyceroporins/genetics ; Drug Resistance/genetics ; Humans ; Melarsoprol/pharmacology/*therapeutic use ; Mutation ; Trypanosoma brucei gambiense/drug effects/genetics ; Trypanosomiasis, African/*drug therapy/*parasitology ; }, abstract = {Arsenicals were introduced as monotherapies for the treatment of human African trypanosomiasis, or sleeping sickness, over 100 years ago. Toxicity has always been an issue but these drugs have proven to be both effective and quite durable. Unfortunately, melarsoprol-resistant parasites emerged as early as the 1970s and were widespread by the late 1990s. Resistance was due to mutations affecting an aquaglyceroporin (AQP2), a parasite solute and drug transporter. This is the only example of widespread drug resistance in trypanosomiasis patients for which the genetic basis is known. This link between melarsoprol and AQP2 illustrates how a drug transporter can improve drug selectivity but, at the same time, highlights the risk of resistance when the drug uptake mechanism is dispensable for parasite viability and virulence.}, } @article {pmid29705333, year = {2018}, author = {Nemec, S and Sung, AH and Drouin, J}, title = {Shh signaling influences the phenotype of Pitx1-/- hindlimbs.}, journal = {Developmental biology}, volume = {439}, number = {2}, pages = {65-68}, doi = {10.1016/j.ydbio.2018.04.024}, pmid = {29705333}, issn = {1095-564X}, support = {MOP-123213//CIHR/Canada ; }, mesh = {Animals ; Body Patterning/genetics ; Extremities/embryology ; Forelimb/embryology/metabolism ; Gene Expression Regulation, Developmental/genetics ; Hedgehog Proteins/*genetics/metabolism/*physiology ; Hindlimb/embryology/metabolism ; Homeodomain Proteins/metabolism ; Limb Buds/metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Paired Box Transcription Factors/genetics/*metabolism/physiology ; Phenotype ; Signal Transduction/genetics ; Transcription Factors/metabolism ; }, abstract = {Forelimbs (FLs) and hindlimbs (HLs) develop under the instructive and integrated guidance of signaling centers and transcription factor (TF) action. The development of structures specific to each limb type depends on the limb-specific modulation of these integrated components. Pitx1 is a transcription factor gene expressed in HL, absent in FL, and required for HL-specific patterning and development, in particular for formation of anterior HL skeletal elements. Pitx1 achieves this function by direct TF action on the core limb program, which is largely shared between FL and HL. Shh signaling plays a crucial role in anterior-posterior (AP) patterning in both FL and HL. The present work assessed the relationship between Shh signaling and Pitx1 action for AP patterning. We found that reducing the gene dosage of Shh in the context of the Pitx1-/- HL decreases the severity of the Pitx1-/- phenotype, in particular, the loss of anterior limb structures and the shortening of femur length. However, this did not rescue HL-specific patterning features. Thus, Pitx1 action integrates Shh signaling but not for limb-type-specific patterning.}, } @article {pmid29705332, year = {2018}, author = {Cervantes-Pérez, SA and Espinal-Centeno, A and Oropeza-Aburto, A and Caballero-Pérez, J and Falcon, F and Aragón-Raygoza, A and Sánchez-Segura, L and Herrera-Estrella, L and Cruz-Hernández, A and Cruz-Ramírez, A}, title = {Transcriptional profiling of the CAM plant Agave salmiana reveals conservation of a genetic program for regeneration.}, journal = {Developmental biology}, volume = {442}, number = {1}, pages = {28-39}, doi = {10.1016/j.ydbio.2018.04.018}, pmid = {29705332}, issn = {1095-564X}, mesh = {Agave/*genetics ; Crassulaceae/genetics ; Cytokinins/metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Plant/genetics ; High-Throughput Nucleotide Sequencing ; Indoleacetic Acids/metabolism ; Organogenesis, Plant/*genetics/physiology ; Plant Growth Regulators/genetics ; Plant Leaves/genetics/growth & development ; Regeneration/*genetics ; Transcriptome/genetics ; }, abstract = {In plants, the best characterized plant regeneration process is de novo organogenesis. This type of regeneration is characterized by the formation of a multicellular structure called callus. Calli are induced via phytohormone treatment of plant sections. The callus formation in plants like Agave species with Crassulacean Acid Metabolism (CAM) is poorly studied. In this study, we induced callus formation from Agave salmiana leaves and describe cell arrangement in this tissue. Moreover, we determined and analyzed the transcriptional program of calli, as well as those of differentiated root and leaf tissues, by using RNA-seq. We were able to reconstruct 170,844 transcripts of which 40,644 have a full Open Reading Frame (ORF). The global profile obtained by Next Generation Sequencing (NGS) reveals that several callus-enriched protein coding transcripts are orthologs of previously reported factors highly expressed in Arabidopsis calli. At least 62 genes were differentially expressed in Agave calli, 50 of which were up-regulated. Several of these are actively involved in the perception of, and response to, auxin and cytokinin. Not only are these the first results for the A. salmiana callus, but they provide novel data from roots and leaves of this Agave species, one of the largest non-tree plants in nature.}, } @article {pmid29705331, year = {2018}, author = {Ramalingam, H and Fessler, AR and Das, A and Valerius, MT and Basta, J and Robbins, L and Brown, AC and Oxburgh, L and McMahon, AP and Rauchman, M and Carroll, TJ}, title = {Disparate levels of beta-catenin activity determine nephron progenitor cell fate.}, journal = {Developmental biology}, volume = {440}, number = {1}, pages = {13-21}, pmid = {29705331}, issn = {1095-564X}, support = {F32 DK060319/DK/NIDDK NIH HHS/United States ; R37 DK054364/DK/NIDDK NIH HHS/United States ; R01 DK054364/DK/NIDDK NIH HHS/United States ; P30 DK079328/DK/NIDDK NIH HHS/United States ; R01 DK090127/DK/NIDDK NIH HHS/United States ; R01 DK098563/DK/NIDDK NIH HHS/United States ; R01 DK078161/DK/NIDDK NIH HHS/United States ; R01 DK080004/DK/NIDDK NIH HHS/United States ; R01 DK095057/DK/NIDDK NIH HHS/United States ; R24 DK106743/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Gene Expression Regulation/genetics ; Kidney/cytology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Nephrons/embryology/*physiology ; Signal Transduction/physiology ; Stem Cells/metabolism/physiology ; Transcription Factors/metabolism ; Wnt Proteins/metabolism ; Wnt Signaling Pathway/physiology ; beta Catenin/*metabolism/*physiology ; }, abstract = {Formation of a functional kidney depends on the balance between renewal and differentiation of nephron progenitors. Failure to sustain this balance can lead to kidney failure or stem cell tumors. For nearly 60 years, we have known that signals from an epithelial structure known as the ureteric bud were essential for maintaining this balance. More recently it was discovered that one molecule, Wnt9b, was necessary for both renewal and differentiation of the nephron progenitor cells. How one ligand signaling through one transcription factor promoted two seemingly contradictory cellular processes was unclear. In this study, we show that Wnt9b/beta-catenin signaling alone is sufficient to promote both renewal and differentiation. Moreover, we show that discrete levels of beta-catenin can promote these two disparate fates, with low levels fostering progenitor renewal and high levels driving differentiation. These results provide insight into how Wnt9b regulates distinct target genes that balance nephron progenitor renewal and differentiation.}, } @article {pmid29704470, year = {2018}, author = {Tabin, JA and Aspiras, A and Martineau, B and Riddle, M and Kowalko, J and Borowsky, R and Rohner, N and Tabin, CJ}, title = {Temperature preference of cave and surface populations of Astyanax mexicanus.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {338-344}, pmid = {29704470}, issn = {1095-564X}, support = {R01 HD089934/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Characiformes/*physiology ; *Crosses, Genetic ; *Ecosystem ; *Quantitative Trait, Heritable ; *Temperature ; }, abstract = {Little is known about the genetic basis of behavioral choice, such as temperature preference, especially in natural populations. Thermal preference can play a key role in habitat selection, for example in aquatic species. Examining this behavior on a genetic level requires access to individuals or populations of the same species that display distinct temperature preferences. Caves provide a uniquely advantageous setting to tackle this problem, as animals colonizing caves encounter an environment that generally has a different, and far more stable, annual temperature than what is encountered on the outside. Here, we focus on cave and surface populations of Astyanax mexicanus, the Mexican tetra, and examine temperature preference and strength of temperature preference (reflected in the percent of time spent at the optimal temperature). We used a tank with a stable temperature gradient and automated tracking software to follow individual fish from each population. We found that distinct populations of A. mexicanus display differences in both temperature preference and strength of preference. Hybrid crosses established that these are multigenic traits that segregate independently from one another. Temperature preference in many aquatic animals is known to shift towards warmer temperatures following infection with parasites (akin to a fever response in humans). While surface fish infected by the ectoparasite Gyrodactylus turnbulli (a gill fluke) displayed a strong fever response, cavefish showed a significantly attenuated fever response. This work establishes A. mexicanus as a genetically tractable system in which differences in temperature preference can be studied in naturally evolved populations.}, } @article {pmid29704124, year = {2018}, author = {Shen, Q and Wang, Y and Shen, J and Jiang, L and Wei, C and Zhang, H}, title = {Growth and Cell Properties of Modified Lactobacillus plantarum CICC21001 with Supplementing C18-FFAs to Growth Medium in vitro.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1133-1141}, pmid = {29704124}, issn = {1432-0991}, mesh = {Acids/toxicity ; Bacterial Adhesion ; Bile Acids and Salts/toxicity ; Culture Media/*chemistry ; Fatty Acids, Nonesterified/*metabolism ; Lactobacillus plantarum/growth & development/metabolism/*physiology ; Microbial Viability/drug effects ; Probiotics/metabolism ; Stress, Physiological ; Surface Properties ; Temperature ; }, abstract = {Fatty acids (FAs) are one of the important factors that can influence cell growth and membrane composition. The aim of this study was to investigate the influence of supplementing MLM+ growth medium with C18 free fatty acids (C18-FFAs), including stearic (C18:0), oleic (C18:1), linoleic (C18:2), and linolenic (C18:3) acid, on the growth of Lactobacillus plantarum CICC21001 by forming ion pairs with lysine to increase the solubility of FAs in liquid medium. The utilization of C18-FFAs was further confirmed by GC-FID. The investigation of cell properties, including cell surface hydrophobicity and zeta potential, was carried out for the modified L. plantarum and control group (non-supplementation). Furthermore, cell survival was measured in real time under heat (at 55 and 62 °C for 5 min), acid (pH 2.2), and bile salt stress. Our results indicated that the action of L. plantarum was modulated by assimilating C18-FFAs. This study suggested that C18-FFAs altered the life cycles and physiochemical properties of L. plantarum, which provided a guideline for probiotics production and their medical application.}, } @article {pmid29703939, year = {2018}, author = {Rutledge, GG and Amato, R}, title = {Juggling resistance mutations.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {332}, doi = {10.1038/s41579-018-0008-1}, pmid = {29703939}, issn = {1740-1534}, } @article {pmid29703755, year = {2018}, author = {Schröter, C and Lee, JC and Schultz, T}, title = {Mass-correlated rotational Raman spectra with high resolution, broad bandwidth, and absolute frequency accuracy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5072-5076}, pmid = {29703755}, issn = {1091-6490}, abstract = {We present mass-correlated rotational alignment spectroscopy, based on the optical excitation of a coherent rotational quantum wave and the observation of temporal wave interferences in a mass spectrometer. Combined electronic and opto-mechanical delays increased the observation time and energy resolution by an order of magnitude compared with preceding time-domain measurements. Rotational transition frequencies were referenced to an external clock for accurate absolute frequency measurements. Rotational Raman spectra for six naturally occurring carbon disulfide isotopologues were resolved with 3 MHz resolution over a spectral range of 500 GHz. Rotational constants were determined with single-kilohertz accuracy, competitive with state-of-the-art frequency domain measurements.}, } @article {pmid29703754, year = {2018}, author = {Milic, B and Chakraborty, A and Han, K and Bassik, MC and Block, SM}, title = {KIF15 nanomechanics and kinesin inhibitors, with implications for cancer chemotherapeutics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4613-E4622}, pmid = {29703754}, issn = {1091-6490}, support = {DP2 HD084069/HD/NICHD NIH HHS/United States ; R37 GM057035/GM/NIGMS NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; U01 CA199216/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/*pharmacology ; Cell Movement/drug effects ; Cell Proliferation/drug effects ; HeLa Cells ; Humans ; Kinesin/*antagonists & inhibitors/genetics/metabolism ; Microtubules/drug effects/*pathology ; Neoplasms/drug therapy/*pathology ; Small Molecule Libraries/*pharmacology ; Spindle Apparatus/drug effects ; }, abstract = {Eg5, a mitotic kinesin, has been a target for anticancer drug development. Clinical trials of small-molecule inhibitors of Eg5 have been stymied by the development of resistance, attributable to mitotic rescue by a different endogenous kinesin, KIF15. Compared with Eg5, relatively little is known about the properties of the KIF15 motor. Here, we employed single-molecule optical-trapping techniques to define the KIF15 mechanochemical cycle. We also studied the inhibitory effects of KIF15-IN-1, an uncharacterized, commercially available, small-molecule inhibitor, on KIF15 motility. To explore the complementary behaviors of KIF15 and Eg5, we also scored the effects of small-molecule inhibitors on admixtures of both motors, using both a microtubule (MT)-gliding assay and an assay for cancer cell viability. We found that (i) KIF15 motility differs significantly from Eg5; (ii) KIF15-IN-1 is a potent inhibitor of KIF15 motility; (iii) MT gliding powered by KIF15 and Eg5 only ceases when both motors are inhibited; and (iv) pairing KIF15-IN-1 with Eg5 inhibitors synergistically reduces cancer cell growth. Taken together, our results lend support to the notion that a combination drug therapy employing both inhibitors may be a viable strategy for overcoming chemotherapeutic resistance.}, } @article {pmid29703753, year = {2018}, author = {Hodges, HL and Brown, RA and Crooks, JA and Weibel, DB and Kiessling, LL}, title = {Imaging mycobacterial growth and division with a fluorogenic probe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5271-5276}, pmid = {29703753}, issn = {1091-6490}, support = {R33 DK070297/DK/NIDDK NIH HHS/United States ; P50 GM064598/GM/NIGMS NIH HHS/United States ; T32 GM008505/GM/NIGMS NIH HHS/United States ; S10 RR013790/RR/NCRR NIH HHS/United States ; F31 GM108408/GM/NIGMS NIH HHS/United States ; R01 AI126592/AI/NIAID NIH HHS/United States ; F32 GM113454/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/metabolism ; Cell Division ; Cell Wall/*metabolism ; Cord Factors/*metabolism ; Corynebacterium glutamicum/*growth & development ; Fluorescence ; Fluorescent Dyes/*chemistry ; Humans ; Image Processing, Computer-Assisted/*methods ; Mycobacterium tuberculosis/*growth & development ; Peptidoglycan/metabolism ; Tuberculosis/*diagnosis/metabolism/microbiology ; }, abstract = {Control and manipulation of bacterial populations requires an understanding of the factors that govern growth, division, and antibiotic action. Fluorescent and chemically reactive small molecule probes of cell envelope components can visualize these processes and advance our knowledge of cell envelope biosynthesis (e.g., peptidoglycan production). Still, fundamental gaps remain in our understanding of the spatial and temporal dynamics of cell envelope assembly. Previously described reporters require steps that limit their use to static imaging. Probes that can be used for real-time imaging would advance our understanding of cell envelope construction. To this end, we synthesized a fluorogenic probe that enables continuous live cell imaging in mycobacteria and related genera. This probe reports on the mycolyltransferases that assemble the mycolic acid membrane. This peptidoglycan-anchored bilayer-like assembly functions to protect these cells from antibiotics and host defenses. Our probe, quencher-trehalose-fluorophore (QTF), is an analog of the natural mycolyltransferase substrate. Mycolyltransferases process QTF by diverting their normal transesterification activity to hydrolysis, a process that unleashes fluorescence. QTF enables high contrast continuous imaging and the visualization of mycolyltransferase activity in cells. QTF revealed that mycolyltransferase activity is augmented before cell division and localized to the septa and cell poles, especially at the old pole. This observed localization suggests that mycolyltransferases are components of extracellular cell envelope assemblies, in analogy to the intracellular divisomes and polar elongation complexes. We anticipate QTF can be exploited to detect and monitor mycobacteria in physiologically relevant environments.}, } @article {pmid29703586, year = {2018}, author = {Hackenberg, M and Kotsyfakis, M}, title = {Exosome-Mediated Pathogen Transmission by Arthropod Vectors.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {549-552}, doi = {10.1016/j.pt.2018.04.001}, pmid = {29703586}, issn = {1471-5007}, mesh = {Animals ; Arthropod Vectors/*parasitology ; Exosomes/*physiology ; *Host-Parasite Interactions ; Humans ; Parasitic Diseases/*transmission ; Ticks/*parasitology ; }, abstract = {Recent molecular and cellular studies have highlighted a potentially important role for tick exosomes in parasite transmission. Here we summarize evolving hypotheses about the largely unknown cellular events that may take place at the tick-host-pathogen interface, focusing on a potential role for arthropod exosomes in this tripartite interaction.}, } @article {pmid29703496, year = {2018}, author = {Elwell, C and Engel, J}, title = {Emerging Role of Retromer in Modulating Pathogen Growth.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {769-780}, pmid = {29703496}, issn = {1878-4380}, support = {R01 AI122747/AI/NIAID NIH HHS/United States ; R21 AI105561/AI/NIAID NIH HHS/United States ; }, abstract = {Intracellular pathogens have developed elegant mechanisms to modulate host endosomal trafficking. The highly conserved retromer pathway has emerged as an important target of viruses and intravacuolar bacteria. Some pathogens require retromer function to survive. For others, retromer activity restricts intracellular growth; these pathogens must disrupt retromer function to survive. In this review, we discuss recent paradigm changes to the current model for retromer assembly and cargo selection. We highlight how the study of pathogen effectors has contributed to these fundamental insights, with a special focus on the biology and structure of two recently described bacterial effectors, Chlamydia trachomatis IncE and Legionella pneumophila RidL. These two pathogens employ distinct strategies to target retromer components and overcome restriction of intracellular growth imposed by retromer.}, } @article {pmid29703495, year = {2018}, author = {Kinchen, VJ and Cox, AL and Bailey, JR}, title = {Can Broadly Neutralizing Monoclonal Antibodies Lead to a Hepatitis C Virus Vaccine?.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {854-864}, doi = {10.1016/j.tim.2018.04.002}, pmid = {29703495}, issn = {1878-4380}, support = {U19 AI088791/AI/NIAID NIH HHS/United States ; }, abstract = {While licensed vaccines elicit protective antibody responses against a variety of viral infections, an effective vaccine for hepatitis C virus (HCV) has remained elusive. The extraordinary genetic diversity of HCV and the ability of the virus to evade the immune response have hindered vaccine development efforts. However, recent studies have greatly expanded the number of well characterized broadly neutralizing human monoclonal antibodies (bNAbs) against HCV. These bNAbs target relatively conserved HCV epitopes, prevent HCV infection in animal models, and are associated with spontaneous clearance of human HCV infection. In this review, recent high-resolution bNAb epitope mapping and structural analysis of bNAb-epitope complexes that may serve as a guide for vaccine development are discussed along with major obstacles.}, } @article {pmid29703494, year = {2018}, author = {Wang, W and Han, GZ}, title = {The Expanding Diversity of RNA Viruses in Vertebrates.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {465-466}, doi = {10.1016/j.tim.2018.04.003}, pmid = {29703494}, issn = {1878-4380}, mesh = {Animals ; RNA ; RNA Viruses/*genetics ; *Vertebrates ; }, abstract = {The diversity of RNA viruses in vertebrates remains largely unexplored. The discovery of 214 novel vertebrate-associated RNA viruses will likely help us to understand the diversity and evolution of RNA viruses in vertebrates.}, } @article {pmid29703265, year = {2018}, author = {Crowley, ST and Kataoka, K and Itaka, K}, title = {Combined CatWalk Index: an improved method to measure mouse motor function using the automated gait analysis system.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {263}, pmid = {29703265}, issn = {1756-0500}, support = {JP15H03017//Japan Society for the Promotion of Science/ ; 16K15642//Japan Society for the Promotion of Science/ ; 17F17410//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Behavior, Animal/*physiology ; Biomechanical Phenomena ; Disease Models, Animal ; Female ; Gait/*physiology ; Mice ; Mice, Inbred C57BL ; *Models, Biological ; Motor Activity/*physiology ; Spinal Cord Injuries/*physiopathology ; }, abstract = {OBJECTIVE: Measuring motor function in mice is important for studying models of spinal cord injury (SCI) or other diseases. Several methods exist based on visual observation of mice moving in an open field. Though these methods require very little equipment, observers must be trained, and the possibility of human error or subjectivity cannot be eliminated. The Noldus CatWalk XT Automated Gait Analysis system assesses mouse motor function by taking high-resolution videos of the mice, with specialized software to measure several aspects of the animal's gait. This instrument reduces the possibility of human error, but it is not always clear what data is important for assessing motor function. This study used data collected during mouse SCI experiments to create a simple mathematical model that combines the data collected by the CatWalk system into a single score, the Combined CatWalk Index or CCI.

RESULTS: The CCI system produces similar results to the Basso Mouse Scale or the CatWalk's Step Sequence Regularity Index. However, the CCI has a significantly smaller coefficient of variation than either other method. Additionally, CCI scoring shows slightly better correlation with impact force. The CCI system is likely to be a useful tool for SCI research.}, } @article {pmid29703257, year = {2018}, author = {Yang, L and Gu, W and Cheung, KH and Yan, L and Tong, BC and Jiang, Y and Yang, J}, title = {InsP3R-SEC5 interaction on phagosomes modulates innate immunity to Candida albicans by promoting cytosolic Ca2+ elevation and TBK1 activity.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {46}, pmid = {29703257}, issn = {1741-7007}, abstract = {BACKGROUND: Candida albicans (C. albicans) invasion triggers antifungal innate immunity, and the elevation of cytoplasmic Ca2+ levels via the inositol 1,4,5-trisphosphate receptor (InsP3R) plays a critical role in this process. However, the molecular pathways linking the InsP3R-mediated increase in Ca2+ and immune responses remain elusive.

RESULTS: In the present study, we find that during C. albicans phagocytosis in macrophages, exocyst complex component 2 (SEC5) promotes InsP3R channel activity by binding to its C-terminal α-helix (H1), increasing cytosolic Ca2+ concentrations ([Ca2+]c). Immunofluorescence reveals enriched InsP3R-SEC5 complex formation on phagosomes, while disruption of the InsP3R-SEC5 interaction by recombinant H1 peptides attenuates the InsP3R-mediated Ca2+ elevation, leading to impaired phagocytosis. Furthermore, we show that C. albicans infection promotes the recruitment of Tank-binding kinase 1 (TBK1) by the InsP3R-SEC5 interacting complex, leading to the activation of TBK1. Subsequently, activated TBK1 phosphorylates interferon regulatory factor 3 (IRF-3) and mediates type I interferon responses, suggesting that the InsP3R-SEC5 interaction may regulate antifungal innate immune responses not only by elevating cytoplasmic Ca2+ but also by activating the TBK1-IRF-3 pathway.

CONCLUSIONS: Our data have revealed an important role of the InsP3R-SEC5 interaction in innate immune responses against C. albicans.}, } @article {pmid29703250, year = {2018}, author = {Udeshika, WAE and Herath, HMMTB and Dassanayake, SUB and Pahalagamage, SP and Kulatunga, A}, title = {A case report of giant pancreatic pseudocyst following acute pancreatitis: experience with endoscopic internal drainage.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {262}, pmid = {29703250}, issn = {1756-0500}, mesh = {Adult ; Drainage/*methods ; Endoscopy, Digestive System/*methods ; Endosonography/*methods ; Humans ; Male ; Pancreatic Pseudocyst/*diagnostic imaging/etiology/*surgery ; Pancreatitis/*complications ; }, abstract = {BACKGROUND: Pancreatic cysts are being diagnosed more frequently because of the increasing usage of imaging techniques. A pseudocyst with the major diameter of 10 cm is termed as a giant cyst. Asymptomatic pseudo-cysts up to 6 cm in diameter can be safely observed and monitored without intervention, but larger and symptomatic pseudocysts require intervention.

CASE PRESENTATION: A 27-year-old Sri Lankan male, with history of heavy alcohol use, presented with progressive abdominal distension following an episode of acute pancreatitis. Contrast enhanced CT scan of the abdomen showed a large multilocular cystic lesion almost occupying the entire abdominal cavity and displacing the liver medially and the right dome of the diaphragm superiorly. The largest locule in the right side measured as 30 cm × 15 cm × 14 cm. Endoscopic ultrasound guided drainage of the cyst was performed. The cyst was entered into with an electrocautery-assisted cystotome and a lumen-opposing metal stent was deployed under fluoroscopic vision followed by dilatation with a 10 mm controlled radial expansion balloon. Repeat endoscopic ultrasound was done a week later due to persistence of the collection and a second stent was inserted. Then 10 French gauge × 10 cm double ended pigtails were inserted through both stents. The cysts were not visualized on subsequent Ultra sound scans. Stent removal was done after 3 weeks, leaving the pigtails insitu. The patient made an uneventful recovery.

CONCLUSION: Giant pancreatic pseudocysts are rare and earlier drainage is recommended before clinical deterioration. Some experts suggest that cystogastrostomy may not be appropriate for the treatment of giant pancreatic pseudocysts and in some instances external drainage of giant pancreatic pseudocysts may be safer than cystogastrostomy. Video-assisted pancreatic necrosectomy with internal drainage and laparoscopic cystogastrostomy were also tried with a good outcome. With our experience we suggest endoscopic guided internal drainage as a possible initial method of management of a giant pseudo cyst. However long-term follow up is needed with repeated imaging and endoscopy. In instances where the primary endoscopic internal drainage fails, surgical procedures may be required as a second line option.}, } @article {pmid29703247, year = {2018}, author = {Zeng, Q and Rodrigo, A}, title = {Neutral models of short-term microbiome dynamics with host subpopulation structure and migration limitation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {80}, pmid = {29703247}, issn = {2049-2618}, mesh = {Biological Evolution ; Computational Biology/*methods ; *Computer Simulation ; Host Microbial Interactions/*physiology ; Humans ; Microbiota/*physiology ; *Models, Biological ; }, abstract = {BACKGROUND: Most empirical studies tend to focus on microbiome dynamics within hosts or microbiome compositional differences between hosts over short periods. However, there is still a dearth of formal models that allow us to investigate the observed short-term dynamics of microbiomes under a unified ecological and evolutionary framework. In our previous study, we developed a computational agent-based neutral framework that simulates microbiome dynamics spanning many host generations with the added dimension of a genealogy of hosts. Although this long-term framework revealed interesting microbial diversity patterns under a simple but plausible evolutionary process and provided a platform for future elaboration of more complex systems, it does not allow us to explore microbiome dynamics within a single host generation.

METHODS: In this paper, we developed a computational, agent-based, forward-time framework of microbiome dynamics within a single host generation. As we have done under our neutral long-term models, we incorporate neutral processes of environmental microbiome assembly and microbe acquisition from parents and environment. We also incorporate a Moran genealogical model of hosts, so that the dynamics of microbiome evolution can be studied within a single host generation. Furthermore, we allow host subpopulation structure and host migration to affect microbiome recruitment.

RESULTS: We show that microbiome diversity within hosts increases monotonically with increases in environmental contribution, while microbiome diversity between hosts increases with increasing parental inheritance. Host population division and dispersal limitation under high host contribution further shaped the patterns by elevating microbiome differences between hosts and depressing microbial diversity within hosts. Microbiome diversity within the whole population showed strong temporal stability regardless of the modes of microbiome acquisition and subpopulation structures.

CONCLUSIONS: We present a computational framework that integrates various processes including host genealogy, microbe recruitment, and host dispersal limitation acting on the short-term dynamics of microbiomes. Our framework demonstrates that the neutral dynamics of microbiomes within a population of hosts is strongly influenced by transmission mode and shared environment.}, } @article {pmid29703228, year = {2018}, author = {Kitamura, T and Bouakhasith, V and Phounphenghack, K and Pathammavong, C and Xeuatvongsa, A and Norizuki, M and Okabayashi, H and Mori, Y and Machida, M and Hachiya, M}, title = {Assessment of temperatures in the vaccine cold chain in two provinces in Lao People's Democratic Republic: a cross-sectional pilot study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {261}, pmid = {29703228}, issn = {1756-0500}, support = {27-4//The Grant of National Center for Global Health and Medicine/ ; 28-1//The Grant of National Center for Global Health and Medicine/ ; AMED//Research Program on Emerging and Re-emerging Infectious Diseases from Japan Agency for Medical Research and Development/ ; }, mesh = {*Cold Temperature ; Cross-Sectional Studies ; Humans ; Laos ; Pilot Projects ; Refrigeration/*standards ; Vaccines/*standards ; }, abstract = {OBJECTIVE: All childhood vaccines, except the oral polio vaccine, should be kept at 2-8 °C, since the vaccine potency can be damaged by heat or freezing temperature. A temperature monitoring study conducted in 2008-2009 reported challenges in cold chain management from the provincial level downwards. The present cross-sectional pilot study aimed to assess the current status of the cold chain in two provinces (Saravan and Xayabouly) of Lao People's Democratic Republic between March-April 2016. Two types of temperature data loggers recorded the temperatures and the proportions of time exposed to < 0 or > 8 °C were calculated.

RESULTS: The temperature remained within the appropriate range in the central and provincial storages. However, the vaccines were frequently exposed to > 8 °C in Saravan and < 0 °C in Xayabouly in the district storage. Vaccines were exposed to > 8 °C during the transportation in Saravan and to both > 8 and < 0 °C in Xayabouly. Thus, challenges in managing the cold chain in the district storage and during transportation remain, despite improvements at the provincial storage. A detailed up-to-date nationwide analysis of the current situation of the cold chain is warranted to identify the most appropriate intervention to tackle the remaining challenges.}, } @article {pmid29703224, year = {2018}, author = {Musa, IR and Ahmed, MON and Sabir, EI and Alsheneber, IF and Ibrahim, EME and Mohamed, GB and Awadallah, RE and Abbas, T and Gasim, GI}, title = {Factors associated with amputation among patients with diabetic foot ulcers in a Saudi population.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {260}, pmid = {29703224}, issn = {1756-0500}, mesh = {Aged ; Amputation/*statistics & numerical data ; Diabetic Foot/blood/epidemiology/pathology/*surgery ; Female ; Humans ; Male ; Middle Aged ; Prospective Studies ; Saudi Arabia/epidemiology ; }, abstract = {OBJECTIVES: A prospective study was conducted at the Armed Forces Hospital, Dhahran, Saudi Arabia, between January 2015 and December 2016 to identify the risk factors associated with amputation among diabetic foot ulcers DFUs patients.

RESULTS: In total, 82 patients were recruited. Fifty-five of the patients were males (67.07%), the mean (SD) age of the participants was 60 (± 11.4) years, the mean duration of diabetes was 8.5 (± 3.7) years, and the mean haemoglobin A1c was 4.8 (± 2.8)%. In Univariate analysis, older age and high white blood cell count (WBC) were factors associated with amputation (OR = 1.1, 95% CI = 1-1.1, P = 0.012; and OR = 383, 95% CI = 7.9-18,665, P = 0.003, respectively). On the other hand, an ischaemic ulcer was half as likely as a neuropathic ulcer to lead to amputation (OR = 0.5, 95% CI = 0.3-0.9, P = 0.036), and a higher Wagner's grade was found to be protective against amputation OR = 14.5, 95% CI = 4.3-49.4, P < 0.001. In conclusion, the current study showed that although a number of factors have been described to complicate diabetic ulcers by different researchers, none of those factors were identified in our study apart from older age and high WBC.}, } @article {pmid29703213, year = {2018}, author = {Roberts, SA and Prescott, MC and Davidson, AJ and McLean, L and Beynon, RJ and Hurst, JL}, title = {Individual odour signatures that mice learn are shaped by involatile major urinary proteins (MUPs).}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {48}, pmid = {29703213}, issn = {1741-7007}, support = {BB/J002631/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Reliable recognition of individuals requires phenotypic identity signatures that are both individually distinctive and appropriately stable over time. Individual-specific vocalisations or visual patterning are well documented among birds and some mammals, whilst odours play a key role in social recognition across many vertebrates and invertebrates. Less well understood, though, is whether individuals are recognised through variation in cues that arise incidentally from a wide variety of genetic and non-genetic differences between individuals, or whether animals evolve distinctive polymorphic signals to advertise identity reliably. As a bioassay to understand the derivation of individual-specific odour signatures, we use female attraction to the individual odours of male house mice (Mus musculus domesticus), learned on contact with a male's scent marks.

RESULTS: Learned volatile odour signatures are determined predominantly by individual differences in involatile major urinary protein (MUP) signatures, a specialised set of communication proteins that mice secrete in their urine. Recognition of odour signatures in genetically distinct mice depended on differences in individual MUP genotype. Direct manipulation using recombinant MUPs confirmed predictable changes in volatile signature recognition according to the degree of matching between MUP profiles and the learned urine template. Both the relative amount of the male-specific MUP pheromone darcin, which induces odour learning, and other MUP isoforms influenced learned odour signatures. By contrast, odour recognition was not significantly influenced by individual major histocompatibility complex genotype. MUP profiles shape volatile odour signatures through isoform-specific differences in binding and release of urinary volatiles from scent deposits, such that volatile signatures were recognised from the urinary protein fraction alone. Manipulation using recombinant MUPs led to quantitative changes in the release of known MUP ligands from scent deposits, with MUP-specific and volatile-specific effects.

CONCLUSIONS: Despite assumptions that many genes contribute to odours that can be used to recognise individuals, mice have evolved a polymorphic combinatorial MUP signature that shapes distinctive volatile signatures in their scent. Such specific signals may be more prevalent within complex body odours than previously realised, contributing to the evolution of phenotypic diversity within species. However, differences in selection may also result in species-specific constraints on the ability to recognise individuals through complex body scents.}, } @article {pmid29703197, year = {2018}, author = {Giribet, G}, title = {Phylogenomics resolves the evolutionary chronicle of our squirting closest relatives.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {49}, pmid = {29703197}, issn = {1741-7007}, mesh = {Animals ; Genome ; *Phylogeny ; *Urochordata ; }, abstract = {A recent paper in BMC Biology has resolved the family relationships of sea squirts, one of our closest invertebrate relatives, by using a large phylogenomic data set derived from available genomes and newly generated transcriptomes. The work confirms previous ideas that ascidians (the sea squirts) are not monophyletic, as they include some pelagic jelly-like relatives, and proposes a chronogram for a group that has been difficult to resolve due to their accelerated genome evolution.See research article: https://bmcbiol.biomedcentral.com/articles/10.1186/s12915-018-0499-2.}, } @article {pmid29703159, year = {2018}, author = {Teran Hidalgo, SJ and Ma, S}, title = {Clustering multilayer omics data using MuNCut.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {198}, pmid = {29703159}, issn = {1471-2164}, support = {R03 CA216017/CA/NCI NIH HHS/United States ; R03CA216017//National Institutes of Health/ ; 2016LD001//National Bureau of Statistics of China/ ; }, mesh = {Breast Neoplasms/*genetics ; Cluster Analysis ; Computational Biology/*methods ; Epigenomics ; Female ; Genomics ; Humans ; Ovarian Neoplasms/*genetics ; Software ; }, abstract = {BACKGROUND: Omics profiling is now a routine component of biomedical studies. In the analysis of omics data, clustering is an essential step and serves multiple purposes including for example revealing the unknown functionalities of omics units, assisting dimension reduction in outcome model building, and others. In the most recent omics studies, a prominent trend is to conduct multilayer profiling, which collects multiple types of genetic, genomic, epigenetic and other measurements on the same subjects. In the literature, clustering methods tailored to multilayer omics data are still limited. Directly applying the existing clustering methods to multilayer omics data and clustering each layer first and then combing across layers are both "suboptimal" in that they do not accommodate the interconnections within layers and across layers in an informative way.

METHODS: In this study, we develop the MuNCut (Multilayer NCut) clustering approach. It is tailored to multilayer omics data and sufficiently accounts for both across- and within-layer connections. It is based on the novel NCut technique and also takes advantages of regularized sparse estimation. It has an intuitive formulation and is computationally very feasible. To facilitate implementation, we develop the function muncut in the R package NcutYX.

RESULTS: Under a wide spectrum of simulation settings, it outperforms competitors. The analysis of TCGA (The Cancer Genome Atlas) data on breast cancer and cervical cancer shows that MuNCut generates biologically meaningful results which differ from those using the alternatives.

CONCLUSIONS: We propose a more effective clustering analysis of multiple omics data. It provides a new venue for jointly analyzing genetic, genomic, epigenetic and other measurements.}, } @article {pmid29703154, year = {2018}, author = {Tremblay, BL and Guénard, F and Lamarche, B and Pérusse, L and Vohl, MC}, title = {Familial resemblances in human whole blood transcriptome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {300}, pmid = {29703154}, issn = {1471-2164}, mesh = {Child ; *Epigenesis, Genetic ; Fathers ; Female ; *Gene Expression Regulation ; *Genetics, Population ; *Genome, Human ; High-Throughput Nucleotide Sequencing ; Humans ; Leukocytes, Mononuclear/*metabolism ; Male ; Mothers ; *Transcriptome ; }, abstract = {BACKGROUND: Considering the implication of gene expression in the susceptibility of chronic diseases and the familial clustering of chronic diseases, the study of familial resemblances in gene expression levels is then highly relevant. Few studies have considered the contribution of both genetic and common environmental effects to familial resemblances in whole blood gene expression levels. The objective is to quantify the contribution of genetic and common environmental effects in the familial resemblances of whole blood genome-wide gene expression levels. We also make comparisons with familial resemblances in blood leukocytes genome-wide DNA methylation levels in the same cohort in order to further investigate biological mechanisms.

RESULTS: Maximal heritability, genetic heritability, and common environmental effect were computed for all probes (20.6%, 15.6%, and 5.0% respectively) and for probes showing a significant familial effect (78.1%, 60.1%, and 18.0% respectively). Pairwise phenotypic correlations between gene expression and DNA methylation levels adjusted for blood cell heterogeneity were computed for probes showing significant familial effect. A total of 78 probe pairs among the 7,618,401 possible pairs passed Bonferroni correction (corrected P-value = 6.56 × 10- 9). Significant genetic correlations between gene expression and DNA methylation levels were found for 25 probe pairs (absolute genetic correlation of 0.97).

CONCLUSIONS: Familial resemblances in gene expression levels were mainly attributable to genetic factors, but common environmental effect also played a role especially in probes showing a significant familial effect. Probes and CpG sites with familial effect seem to be under a strong shared genetic control.}, } @article {pmid29703152, year = {2018}, author = {Bogema, DR and Micallef, ML and Liu, M and Padula, MP and Djordjevic, SP and Darling, AE and Jenkins, C}, title = {Analysis of Theileria orientalis draft genome sequences reveals potential species-level divergence of the Ikeda, Chitose and Buffeli genotypes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {298}, pmid = {29703152}, issn = {1471-2164}, support = {B.AHE.0213//Meat and Livestock Australia/ ; }, mesh = {Animals ; Australia/epidemiology ; Cattle ; DNA, Protozoan/genetics ; *Genome, Protozoan ; Genotype ; Phylogeny ; Protozoan Proteins/*genetics ; Species Specificity ; Theileria/*classification/*genetics/isolation & purification ; Theileriasis/epidemiology/*parasitology ; Whole Genome Sequencing/*methods ; }, abstract = {BACKGROUND: Theileria orientalis (Apicomplexa: Piroplasmida) has caused clinical disease in cattle of Eastern Asia for many years and its recent rapid spread throughout Australian and New Zealand herds has caused substantial economic losses to production through cattle deaths, late term abortion and morbidity. Disease outbreaks have been linked to the detection of a pathogenic genotype of T. orientalis, genotype Ikeda, which is also responsible for disease outbreaks in Asia. Here, we sequenced and compared the draft genomes of one pathogenic (Ikeda) and two apathogenic (Chitose, Buffeli) isolates of T. orientalis sourced from Australian herds.

RESULTS: Using de novo assembled sequences and a single nucleotide variant (SNV) analysis pipeline, we found extensive genetic divergence between the T. orientalis genotypes. A genome-wide phylogeny reconstructed to address continued confusion over nomenclature of this species displayed concordance with prior phylogenetic studies based on the major piroplasm surface protein (MPSP) gene. However, average nucleotide identity (ANI) values revealed that the divergence between isolates is comparable to that observed between other theilerias which represent distinct species. Analysis of SNVs revealed putative recombination between the Chitose and Buffeli genotypes and also between Australian and Japanese Ikeda isolates. Finally, to inform future vaccine studies, dN/dS ratios and surface location predictions were analysed. Six predicted surface protein targets were confirmed to be expressed during the piroplasm phase of the parasite by mass spectrometry.

CONCLUSIONS: We used whole genome sequencing to demonstrate that the T. orientalis Ikeda, Chitose and Buffeli variants show substantial genetic divergence. Our data indicates that future researchers could potentially consider disease-associated Ikeda and closely related genotypes as a separate species from non-pathogenic Chitose and Buffeli.}, } @article {pmid29703150, year = {2018}, author = {Dunne, MP and Kelly, S}, title = {OMGene: mutual improvement of gene models through optimisation of evolutionary conservation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {307}, pmid = {29703150}, issn = {1471-2164}, support = {637765//H2020 European Research Council/ ; EP/G03706X/1//Engineering and Physical Sciences Research Council/ ; }, mesh = {Algorithms ; Amino Acid Sequence ; Animals ; *Biological Evolution ; Computational Biology ; Databases, Genetic ; Fungi ; Gene Expression Profiling ; Genome ; Genomics ; Mammals ; *Models, Genetic ; Molecular Sequence Annotation ; Plants ; Sequence Alignment ; Sequence Analysis, RNA/*methods ; *Software ; Transcriptome ; }, abstract = {BACKGROUND: The accurate determination of the genomic coordinates for a given gene - its gene model - is of vital importance to the utility of its annotation, and the accuracy of bioinformatic analyses derived from it. Currently-available methods of computational gene prediction, while on the whole successful, frequently disagree on the model for a given predicted gene, with some or all of the variant gene models often failing to match the biologically observed structure. Many prediction methods can be bolstered by using experimental data such as RNA-seq. However, these resources are not always available, and rarely give a comprehensive portrait of an organism's transcriptome due to temporal and tissue-specific expression profiles.

RESULTS: Orthology between genes provides evolutionary evidence to guide the construction of gene models. OMGene (Optimise My Gene) aims to improve gene model accuracy in the absence of experimental data by optimising the consistency of multiple sequence alignments of orthologous genes from multiple species. Using RNA-seq data sets from plants, mammals, and fungi, considering intron/exon junction representation and exon coverage, and assessing the intra-orthogroup consistency of subcellular localisation predictions, we demonstrate the utility of OMGene for improving gene models in annotated genomes.

CONCLUSIONS: We show that significant improvements in the accuracy of gene model annotations can be made, both in established and in de novo annotated genomes, by leveraging information from multiple species.}, } @article {pmid29703149, year = {2018}, author = {da Silva, VH and Laine, VN and Bosse, M and Oers, KV and Dibbits, B and Visser, ME and M A Crooijmans, RP and Groenen, MAM}, title = {CNVs are associated with genomic architecture in a songbird.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {195}, doi = {10.1186/s12864-018-4577-1}, pmid = {29703149}, issn = {1471-2164}, support = {339092 - E-Response//ERC Advanced Grant/ ; }, mesh = {Animals ; Avian Proteins/genetics ; *DNA Copy Number Variations ; Evolution, Molecular ; Female ; Gene Frequency ; *Gene Regulatory Networks ; Male ; Maternal Inheritance ; Phenotype ; Polymorphism, Single Nucleotide ; Selection, Genetic ; Songbirds/*genetics ; }, abstract = {BACKGROUND: Understanding variation in genome structure is essential to understand phenotypic differences within populations and the evolutionary history of species. A promising form of this structural variation is copy number variation (CNV). CNVs can be generated by different recombination mechanisms, such as non-allelic homologous recombination, that rely on specific characteristics of the genome architecture. These structural variants can therefore be more abundant at particular genes ultimately leading to variation in phenotypes under selection. Detailed characterization of CNVs therefore can reveal evolutionary footprints of selection and provide insight in their contribution to phenotypic variation in wild populations.

RESULTS: Here we use genotypic data from a long-term population of great tits (Parus major), a widely studied passerine bird in ecology and evolution, to detect CNVs and identify genomic features prevailing within these regions. We used allele intensities and frequencies from high-density SNP array data from 2,175 birds. We detected 41,029 CNVs concatenated into 8,008 distinct CNV regions (CNVRs). We successfully validated 93.75% of the CNVs tested by qPCR, which were sampled at different frequencies and sizes. A mother-daughter family structure allowed for the evaluation of the inheritance of a number of these CNVs. Thereby, only CNVs with 40 probes or more display segregation in accordance with Mendelian inheritance, suggesting a high rate of false negative calls for smaller CNVs. As CNVRs are a coarse-grained map of CNV loci, we also inferred the frequency of coincident CNV start and end breakpoints. We observed frequency-dependent enrichment of these breakpoints at homologous regions, CpG sites and AT-rich intervals. A gene ontology enrichment analyses showed that CNVs are enriched in genes underpinning neural, cardiac and ion transport pathways.

CONCLUSION: Great tit CNVs are present in almost half of the genes and prominent at repetitive-homologous and regulatory regions. Although overlapping genes under selection, the high number of false negatives make neutrality or association tests on CNVs detected here difficult. Therefore, CNVs should be further addressed in the light of their false negative rate and architecture to improve the comprehension of their association with phenotypes and evolutionary history.}, } @article {pmid29703147, year = {2018}, author = {Shen, B and Jiang, J and Seroussi, E and Liu, GE and Ma, L}, title = {Characterization of recombination features and the genetic basis in multiple cattle breeds.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {304}, pmid = {29703147}, issn = {1471-2164}, support = {2016-67015-24886//National Institute of Food and Agriculture/ ; US-4997-17//United States - Israel Binational Agricultural Research and Development Fund/ ; }, mesh = {Animals ; *Breeding ; Cattle ; Chromosome Mapping ; Female ; Genome-Wide Association Study ; Genotype ; Male ; Meiosis ; *Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; *Recombination, Genetic ; }, abstract = {BACKGROUND: Crossover generated by meiotic recombination is a fundamental event that facilitates meiosis and sexual reproduction. Comparative studies have shown wide variation in recombination rate among species, but the characterization of recombination features between cattle breeds has not yet been performed. Cattle populations in North America count millions, and the dairy industry has genotyped millions of individuals with pedigree information that provide a unique opportunity to study breed-level variations in recombination.

RESULTS: Based on large pedigrees of Jersey, Ayrshire and Brown Swiss cattle with genotype data, we identified over 3.4 million maternal and paternal crossover events from 161,309 three-generation families. We constructed six breed- and sex-specific genome-wide recombination maps using 58,982 autosomal SNPs for two sexes in the three dairy cattle breeds. A comparative analysis of the six recombination maps revealed similar global recombination patterns between cattle breeds but with significant differences between sexes. We confirmed that male recombination map is 10% longer than the female map in all three cattle breeds, consistent with previously reported results in Holstein cattle. When comparing recombination hotspot regions between cattle breeds, we found that 30% and 10% of the hotspots were shared between breeds in males and females, respectively, with each breed exhibiting some breed-specific hotspots. Finally, our multiple-breed GWAS found that SNPs in eight loci affected recombination rate and that the PRDM9 gene associated with hotspot usage in multiple cattle breeds, indicating a shared genetic basis for recombination across dairy cattle breeds.

CONCLUSIONS: Collectively, our results generated breed- and sex-specific recombination maps for multiple cattle breeds, provided a comprehensive characterization and comparison of recombination patterns between breeds, and expanded our understanding of the breed-level variations in recombination features within an important livestock species.}, } @article {pmid29703146, year = {2018}, author = {Chen, F and Zhang, L and Lin, Z and Cheng, ZM}, title = {Identification of a novel fused gene family implicates convergent evolution in eukaryotic calcium signaling.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {306}, pmid = {29703146}, issn = {1471-2164}, support = {CX(14)2051//Priority Academic Program Development of Modern Horticulture Science in Jiangsu Province/ ; SKB2017004//State Key Laboratory of Ecological Pest Control for Fujian and Taiwan Crops/ ; 1009395//Tennessee Agricultural Experiment Station, University of Tennessee/ ; //Wellcome Trust/United Kingdom ; 201406850018//China Scholarship Council/ ; }, mesh = {Animals ; *Biological Evolution ; Calcium/*metabolism ; Calcium Signaling ; *Computational Biology ; Eukaryota/*genetics ; Gene Expression Regulation ; *Gene Fusion ; *Multigene Family ; Phylogeny ; Plants/*genetics ; }, abstract = {BACKGROUND: Both calcium signals and protein phosphorylation responses are universal signals in eukaryotic cell signaling. Currently three pathways have been characterized in different eukaryotes converting the Ca2+ signals to the protein phosphorylation responses. All these pathways have based mostly on studies in plants and animals.

RESULTS: Based on the exploration of genomes and transcriptomes from all the six eukaryotic supergroups, we report here in Metakinetoplastina protists a novel gene family. This family, with a proposed name SCAMK, comprises SnRK3 fused calmodulin-like III kinase genes and was likely evolved through the insertion of a calmodulin-like3 gene into an SnRK3 gene by unequal crossover of homologous chromosomes in meiosis cell. Its origin dated back to the time intersection at least 450 million-year-ago when Excavata parasites, Vertebrata hosts, and Insecta vectors evolved. We also analyzed SCAMK's unique expression pattern and structure, and proposed it as one of the leading calcium signal conversion pathways in Excavata parasite. These characters made SCAMK gene as a potential drug target for treating human African trypanosomiasis.

CONCLUSIONS: This report identified a novel gene fusion and dated its precise fusion time in Metakinetoplastina protists. This potential fourth eukaryotic calcium signal conversion pathway complements our current knowledge that convergent evolution occurs in eukaryotic calcium signaling.}, } @article {pmid29703145, year = {2018}, author = {Hohmann, N and Wolf, EM and Rigault, P and Zhou, W and Kiefer, M and Zhao, Y and Fu, CX and Koch, MA}, title = {Ginkgo biloba's footprint of dynamic Pleistocene history dates back only 390,000 years ago.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {299}, pmid = {29703145}, issn = {1471-2164}, support = {2017YFA0605100//National Key R&D Program of China/ ; IN-1150438//Deutsche Forschungsgemeinschaft (DFG) and Heidelberg University/ ; }, mesh = {*Biological Evolution ; DNA Barcoding, Taxonomic ; Ecosystem ; *Genetic Variation ; *Genetics, Population ; *Genome, Plastid ; Ginkgo biloba/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: At the end of the Pliocene and the beginning of Pleistocene glaciation and deglaciation cycles Ginkgo biloba went extinct all over the world, and only few populations remained in China in relict areas serving as sanctuary for Tertiary relict trees. Yet the status of these regions as refuge areas with naturally existing populations has been proven not earlier than one decade ago. Herein we elaborated the hypothesis that during the Pleistocene cooling periods G. biloba expanded its distribution range in China repeatedly. Whole plastid genomes were sequenced, assembled and annotated, and sequence data was analyzed in a phylogenetic framework of the entire gymnosperms to establish a robust spatio-temporal framework for gymnosperms and in particular for G. biloba Pleistocene evolutionary history.

RESULTS: Using a phylogenetic approach, we identified that Ginkgoatae stem group age is about 325 million years, whereas crown group radiation of extant Ginkgo started not earlier than 390,000 years ago. During repeated warming phases, Gingko populations were separated and isolated by contraction of distribution range and retreated into mountainous regions serving as refuge for warm-temperate deciduous forests. Diversification and phylogenetic splits correlate with the onset of cooling phases when Ginkgo expanded its distribution range and gene pools merged.

CONCLUSIONS: Analysis of whole plastid genome sequence data representing the entire spatio-temporal genetic variation of wild extant Ginkgo populations revealed the deepest temporal footprint dating back to approximately 390,000 years ago. Present-day directional West-East admixture of genetic diversity is shown to be the result of pronounced effects of the last cooling period. Our evolutionary framework will serve as a conceptual roadmap for forthcoming genomic sequence data, which can then provide deep insights into the demographic history of Ginkgo.}, } @article {pmid29703144, year = {2018}, author = {Dürrbaum, M and Kruse, C and Nieken, KJ and Habermann, B and Storchová, Z}, title = {The deregulated microRNAome contributes to the cellular response to aneuploidy.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {197}, doi = {10.1186/s12864-018-4556-6}, pmid = {29703144}, issn = {1471-2164}, support = {STO918/2-2//Deutsche Forschungsgemeinschaft/ ; }, mesh = {3' Untranslated Regions ; 5' Untranslated Regions ; *Aneuploidy ; Cell Line ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; *Gene Regulatory Networks ; HCT116 Cells ; Humans ; MicroRNAs/*genetics/metabolism ; Protein Biosynthesis ; Ribosomes/metabolism ; }, abstract = {BACKGROUND: Aneuploidy, or abnormal chromosome numbers, severely alters cell physiology and is widespread in cancers and other pathologies. Using model cell lines engineered to carry one or more extra chromosomes, it has been demonstrated that aneuploidy per se impairs proliferation, leads to proteotoxic as well as replication stress and triggers conserved transcriptome and proteome changes.

RESULTS: In this study, we analysed for the first time miRNAs and demonstrate that their expression is altered in response to chromosome gain. The miRNA deregulation is independent of the identity of the extra chromosome and specific to individual cell lines. By cross-omics analysis we demonstrate that although the deregulated miRNAs differ among individual aneuploid cell lines, their known targets are predominantly associated with cell development, growth and proliferation, pathways known to be inhibited in response to chromosome gain. Indeed, we show that up to 72% of these targets are downregulated and the associated miRNAs are overexpressed in aneuploid cells, suggesting that the miRNA changes contribute to the global transcription changes triggered by aneuploidy. We identified hsa-miR-10a-5p to be overexpressed in majority of aneuploid cells. Hsa-miR-10a-5p enhances translation of a subset of mRNAs that contain so called 5'TOP motif and we show that its upregulation in aneuploids provides resistance to starvation-induced shut down of ribosomal protein translation.

CONCLUSIONS: Our work suggests that the changes of the microRNAome contribute on one hand to the adverse effects of aneuploidy on cell physiology, and on the other hand to the adaptation to aneuploidy by supporting translation under adverse conditions.}, } @article {pmid29703143, year = {2018}, author = {Santos, PKF and de Souza Araujo, N and Françoso, E and Zuntini, AR and Arias, MC}, title = {Diapause in a tropical oil-collecting bee: molecular basis unveiled by RNA-Seq.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {305}, pmid = {29703143}, issn = {1471-2164}, support = {2012/18531-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2010/50597-5 and 2013/12530-4//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Animals ; Bees/*physiology ; *Diapause, Insect ; *Gene Expression Profiling ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/*methods ; Larva ; *Transcriptome ; Tropical Climate ; }, abstract = {BACKGROUND: Diapause is a natural phenomenon characterized by an arrest in development that ensures the survival of organisms under extreme environmental conditions. The process has been well documented in arthropods. However, its molecular basis has been mainly studied in species from temperate zones, leaving a knowledge gap of this phenomenon in tropical species. In the present study, the Neotropical and solitary bee Tetrapedia diversipes was employed as a model for investigating diapause in species from tropical zones. Being a bivoltine insect, Tetrapedia diversipes produce two generations of offspring per year. The first generation, normally born during the wet season, develops faster than individuals from the second generation, born after the dry season. Furthermore, it has been shown that the development of the progeny, of the second generation, is halted at the 5th larval instar, and remains in larval diapause during the dry season. Towards the goal of gaining a better understanding of the diapause phenomenon we compared the global gene expression pattern, in larvae, from both reproductive generations and during diapause. The results demonstrate that there are similarities in the observed gene expression patterns to those already described for temperate climate models, and also identify diapause-related genes that have not been previously reported in the literature.

RESULTS: The RNA-Seq analysis identified 2275 differentially expressed transcripts, of which 1167 were annotated. Of these genes, during diapause, 352 were upregulated and 815 were downregulated. According to their biological functions, these genes were categorized into the following groups: cellular detoxification, cytoskeleton, cuticle, sterol and lipid metabolism, cell cycle, heat shock proteins, immune response, circadian clock, and epigenetic control.

CONCLUSION: Many of the identified genes have already been described as being related to diapause; however, new genes were discovered, for the first time, in this study. Among those, we highlight: Niemann-Pick type C1, NPC2 and Acyl-CoA binding protein homolog (all involved in ecdysteroid synthesis); RhoBTB2 and SASH1 (associated with cell cycle regulation) and Histone acetyltransferase KAT7 (related to epigenetic transcriptional regulation). The results presented here add important findings to the understanding of diapause in tropical species, thus increasing the comprehension of diapause-related molecular mechanisms.}, } @article {pmid29703142, year = {2018}, author = {Zhang, J and Malo, D and Mott, R and Panthier, JJ and Montagutelli, X and Jaubert, J}, title = {Identification of new loci involved in the host susceptibility to Salmonella Typhimurium in collaborative cross mice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {303}, pmid = {29703142}, issn = {1471-2164}, support = {PhD fellowship//AgroParisTech/ ; ANR 11-CARN 017-01//Association Instituts Carnot (FR)/ ; ANR-10-LABX-62-IBEID//Agence Nationale de la Recherche/ ; ANR11-CARN 016-01//Association Instituts Carnot/ ; }, mesh = {Animals ; Chromosome Mapping ; *Crosses, Genetic ; *Disease Susceptibility ; Female ; Genetic Variation ; Genetics, Population ; Male ; Mice ; Mice, Inbred C57BL ; Phenotype ; *Quantitative Trait Loci ; Salmonella Infections, Animal/*genetics/*microbiology ; Salmonella typhimurium/*physiology ; }, abstract = {BACKGROUND: Salmonella is a Gram-negative bacterium causing a wide range of clinical syndromes ranging from typhoid fever to diarrheic disease. Non-typhoidal Salmonella (NTS) serovars infect humans and animals, causing important health burden in the world. Susceptibility to salmonellosis varies between individuals under the control of host genes, as demonstrated by the identification of over 20 genetic loci in various mouse crosses. We have investigated the host response to S. Typhimurium infection in 35 Collaborative Cross (CC) strains, a genetic population which involves wild-derived strains that had not been previously assessed.

RESULTS: One hundred and forty-eight mice from 35 CC strains were challenged intravenously with 1000 colony-forming units (CFUs) of S. Typhimurium. Bacterial load was measured in spleen and liver at day 4 post-infection. CC strains differed significantly (P < 0.0001) in spleen and liver bacterial loads, while sex and age had no effect. Two significant quantitative trait loci (QTLs) on chromosomes 8 and 10 and one suggestive QTL on chromosome 1 were found for spleen bacterial load, while two suggestive QTLs on chromosomes 6 and 17 were found for liver bacterial load. These QTLs are caused by distinct allelic patterns, principally involving alleles originating from the wild-derived founders. Using sequence variations between the eight CC founder strains combined with database mining for expression in target organs and known immune phenotypes, we were able to refine the QTLs intervals and establish a list of the most promising candidate genes. Furthermore, we identified one strain, CC042/GeniUnc (CC042), as highly susceptible to S. Typhimurium infection.

CONCLUSIONS: By exploring a broader genetic variation, the Collaborative Cross population has revealed novel loci of resistance to Salmonella Typhimurium. It also led to the identification of CC042 as an extremely susceptible strain.}, } @article {pmid29703141, year = {2018}, author = {Zhou, Q and Zhang, S and Chen, F and Liu, B and Wu, L and Li, F and Zhang, J and Bao, M and Liu, G}, title = {Genome-wide identification and characterization of the SBP-box gene family in Petunia.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {193}, doi = {10.1186/s12864-018-4537-9}, pmid = {29703141}, issn = {1471-2164}, support = {37471914//National Natural Science Foundation of China/ ; 31772345//National Natural Science Foundation of China/ ; IRT13065//Ministry of Education of the People's Republic of China (CN)/ ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Conserved Sequence ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant ; Genome, Plant ; Multigene Family ; Petunia/genetics/*metabolism ; Phylogeny ; Plant Proteins/genetics/metabolism ; Sequence Analysis, RNA/methods ; Tissue Distribution ; Transcription Factors/*genetics/*metabolism ; }, abstract = {BACKGROUND: SQUAMOSA PROMOTER BINDING PROTEIN (SBP)-box genes encode a family of plant-specific transcription factors (TFs) that play important roles in many growth and development processes including phase transition, leaf initiation, shoot and inflorescence branching, fruit development and ripening etc. The SBP-box gene family has been identified and characterized in many species, but has not been well studied in Petunia, an important ornamental genus.

RESULTS: We identified 21 putative SPL genes of Petunia axillaris and P. inflata from the reference genome of P. axillaris N and P. inflata S6, respectively, which were supported by the transcriptome data. For further confirmation, all the 21 genes were also cloned from P. hybrida line W115 (Mitchel diploid). Phylogenetic analysis based on the highly conserved SBP domains arranged PhSPLs in eight groups, analogous to those from Arabidopsis and tomato. Furthermore, the Petunia SPL genes had similar exon-intron structure and the deduced proteins contained very similar conserved motifs within the same subgroup. Out of 21 PhSPL genes, fourteen were predicted to be potential targets of PhmiR156/157, and the putative miR156/157 response elements (MREs) were located in the coding region of group IV, V, VII and VIII genes, but in the 3'-UTR regions of group VI genes. SPL genes were also identified from another two wild Petunia species, P. integrifolia and P. exserta, based on their transcriptome databases to investigate the origin of PhSPLs. Phylogenetic analysis and multiple alignments of the coding sequences of PhSPLs and their orthologs from wild species indicated that PhSPLs were originated mainly from P. axillaris. qRT-PCR analysis demonstrated differential spatiotemperal expression patterns of PhSPL genes in petunia and many were expressed predominantly in the axillary buds and/or inflorescences. In addition, overexpression of PhSPL9a and PhSPL9b in Arabidopsis suggested that these genes play a conserved role in promoting the vegetative-to-reproductive phase transition.

CONCLUSION: Petunia genome contains at least 21 SPL genes, and most of the genes are expressed in different tissues. The PhSPL genes may play conserved and diverse roles in plant growth and development, including flowering regulation, leaf initiation, axillary bud and inflorescence development. This work provides a comprehensive understanding of the SBP-box gene family in Petunia and lays a significant foundation for future studies on the function and evolution of SPL genes in petunia.}, } @article {pmid29703140, year = {2018}, author = {Chen, R and Mao, Y and Wang, J and Liu, M and Qiao, Y and Zheng, L and Su, Y and Ke, Q and Zheng, W}, title = {Molecular mechanisms of an antimicrobial peptide piscidin (Lc-pis) in a parasitic protozoan, Cryptocaryon irritans.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {192}, doi = {10.1186/s12864-018-4565-5}, pmid = {29703140}, issn = {1471-2164}, support = {31372504//National Natural Science Foundation of China/ ; 41476118//National Natural Science Foundation of China/ ; 2016NZ0001-4//Major Projects of Science and Technology Department of Fujian Province/ ; 2015I11010045//Fujian Provincial Department of Science and Technology (CN)/ ; 2015N2002-3//Fujian Provincial Department of Science and Technology/ ; }, mesh = {Animals ; Antimicrobial Cationic Peptides/chemical synthesis/*pharmacology ; Ciliophora/drug effects/*genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation/drug effects ; Perciformes/parasitology ; Protozoan Proteins/*genetics ; Sequence Analysis, RNA/methods ; Vesicular Transport Proteins ; }, abstract = {BACKGROUND: Cryptocaryon irritans is an obligate parasitic ciliate protozoan that can infect various commercially important mariculture fish species and cause high lethality and economic loss. Current methods of controlling this parasite with chemicals or antibiotics are widely considered to be environmentally harmful. Piscidins with broad spectrum antibacterial, antifungal and antiviral activities were found to have potent activity against C. irritans. Little, however, has been understood about the killing mechanisms of piscidins in parasites.

RESULTS: In total, 57.12, 50.44, 55.86 and 47.87 million raw reads were generated from untreated theront and trophont, and piscidin (Lc-pis) treated theront and trophont libraries, respectively. After de novo assembly, 966,609 unigenes were generated with an average length of 420 bp: among these, 618,629 unigenes showed identity with sequences in one or more databases, with some showing to be significantly manipulated by Lc-pis treatment. The species classification showed that more than 25.8% unigenes from trophonts were homologous to the large yellow croaker (Larimichthys crocea) and less than 3.8% unigenes from theronts were matched. The homologous unigenes demonstrated that the tissue from host could exist in trophonts and might be transported to parasite via vesicular transports. Our analysis showed that regulatory transcripts were involved in vesicular trafficking. Among transcripts induced by Lc-pis, most genes up-regulated in treated and untreated theronts were involved in cell migration and apoptosis related pathways. Few transcripts were found to be down-regulated in treated and untreated trophonts related to cell structure and migration after treatment.

CONCLUSIONS: This is the first transcriptome analysis of C. irritans exposed to Lc-pis, which enhanced the genomic resources and provided novel insights into molecular mechanisms of ciliates treated by cationic antimicrobial peptide. Our comprehensive transcriptome analysis can facilitate the identification of potential drug targets and vaccines candidates for controlling this devastating fish pathogen.}, } @article {pmid29703139, year = {2018}, author = {Ali, S and Hoven, A and Dress, RJ and Schaal, H and Alferink, J and Scheu, S}, title = {Identification of a novel Dlg2 isoform differentially expressed in IFNβ-producing plasmacytoid dendritic cells.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {194}, doi = {10.1186/s12864-018-4573-5}, pmid = {29703139}, issn = {1471-2164}, support = {Research Commission of the Medical Faculty 30/2016//Heinrich-Heine-Universität Düsseldorf/ ; SCHE692/3-1//Deutsche Forschungsgemeinschaft/ ; SCHE692/4-1//Deutsche Forschungsgemeinschaft/ ; EXC 1003, Grant FF-2014-01 Cells in Motion-Cluster of Excellence//Deutsche Forschungsgemeinschaft/ ; IZKF, Grant Alf3/018/16//Deutsche Forschungsgemeinschaft/ ; FOR 2107, AL 1145/5-2//Deutsche Forschungsgemeinschaft/ ; 14835//Alzheimer Forschung Initiative/ ; }, mesh = {*Alternative Splicing ; Animals ; Bone Marrow/metabolism ; Brain/metabolism ; Cell Membrane/metabolism ; Cell Nucleus/metabolism ; Cytoplasm/metabolism ; Dendritic Cells/cytology/*metabolism ; Gene Expression Profiling ; Gene Knockout Techniques ; Guanylate Kinases/*genetics/*metabolism ; HEK293 Cells ; Humans ; Interferon-beta/*metabolism ; Membrane Proteins/*genetics/*metabolism ; Mice ; NIH 3T3 Cells ; Oligonucleotide Array Sequence Analysis ; Protein Isoforms/metabolism ; Up-Regulation ; }, abstract = {BACKGROUND: The murine discs large homolog 2 (DLG2; post synaptic density 93 (PSD-93); Chapsyn-110) is a member of the membrane-associated guanylate kinase (MAGUK) protein family involved in receptor assembly and associated with signaling enzymes on cell membranes. In neurons, DLG2 protein isoforms derived from alternatively spliced transcripts have been described to bind to NMDA (N-methyl-aspartate) receptors and K channels and to mediate clustering of these channels in the postsynaptic membrane. In myeloid cells of the immune system, such as dendritic cells (DCs), a lack of data exists on the expression or function of DLG2. In cDNA microarray transcriptome analyses, we found Dlg2 highly expressed in a subpopulation of plasmacytoid DCs (pDCs) stimulated to produce type I interferons (IFNs) such as IFNβ.

RESULTS: Using RACE- and RT-PCR as well as immunoprecipitation followed by Western blotting we characterised the differential expression of the Dlg2 splice variants in IFNβ-producing pDCs. Besides Dlg2ɣ this cell population expressed a novel short Dlg2η transcript we termed Dlg2η3. Our expression data were integrated into information from genome databases to obtain a novel and comprehensive overview of the mouse Dlg2 gene architecture. To elucidate the intracellular localisation pattern of protein isoforms, ectopical expression analysis of fluorescently tagged DLG2 splice variants was performed. Here we found an enrichment of the larger isoform DLG2α1 at the plasma membrane while the newly identified shorter (DLG2η) isoform as well as DLG2ɣ were equally distributed throughout the cytoplasm. Additionally, DLG2η was also found in the nucleus. Analysis of Dlg2-knockout mice previously generated by deleting exon 9 surprisingly revealed that the protein for the novel DLG2η isoform was still expressed in the brain and in bone marrow-derived pDCs from mice carrying the homozygous deletion (Dlg2 ΔE9/ΔE9).

CONCLUSION: We describe a novel splice variant of the mouse Dlg2 gene termed Dlg2η and define the differential expression pattern of DLG2 isoforms in IFNβ-producing pDCs. The presence of DLG2η protein in the CNS of Dlg2 ΔE9/ΔE9 mice might influence the phenotype of these mice and has to be taken into account in the interpretation of results regarding the functional role of DLG2 in neuronal postsynaptic membranes.}, } @article {pmid29703138, year = {2018}, author = {Grilli, A and Bengalli, R and Longhin, E and Capasso, L and Proverbio, MC and Forcato, M and Bicciato, S and Gualtieri, M and Battaglia, C and Camatini, M}, title = {Transcriptional profiling of human bronchial epithelial cell BEAS-2B exposed to diesel and biomass ultrafine particles.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {302}, pmid = {29703138}, issn = {1471-2164}, support = {2013-1038//Fondazione Cariplo/ ; Epigenetics Flagship project CNR-MIUR//MIUR/ ; }, mesh = {*Biomass ; Bronchi/cytology/drug effects/*metabolism ; Cells, Cultured ; Epithelial Cells/cytology/drug effects/*metabolism ; *Gene Expression Profiling ; Gene Expression Regulation/*drug effects ; Humans ; Particulate Matter/*adverse effects ; Transcriptome ; Vehicle Emissions/*poisoning ; }, abstract = {BACKGROUND: Emissions from diesel vehicles and biomass burning are the principal sources of primary ultrafine particles (UFP). The exposure to UFP has been associated to cardiovascular and pulmonary diseases, including lung cancer. Although many aspects of the toxicology of ambient particulate matter (PM) have been unraveled, the molecular mechanisms activated in human cells by the exposure to UFP are still poorly understood. Here, we present an RNA-seq time-course experiment (five time point after single dose exposure) used to investigate the differential and temporal changes induced in the gene expression of human bronchial epithelial cells (BEAS-2B) by the exposure to UFP generated from diesel and biomass combustion. A combination of different bioinformatics tools (EdgeR, next-maSigPro and reactome FI app-Cytoscape and prioritization strategies) facilitated the analyses the temporal transcriptional pattern, functional gene set enrichment and gene networks related to cellular response to UFP particles.

RESULTS: The bioinformatics analysis of transcriptional data reveals that the two different UFP induce, since the earliest time points, different transcriptional dynamics resulting in the activation of specific genes. The functional enrichment of differentially expressed genes indicates that the exposure to diesel UFP induces the activation of genes involved in TNFα signaling via NF-kB and inflammatory response, and hypoxia. Conversely, the exposure to ultrafine particles from biomass determines less distinct modifications of the gene expression profiles. Diesel UFP exposure induces the secretion of biomarkers associated to inflammation (CCXL2, EPGN, GREM1, IL1A, IL1B, IL6, IL24, EREG, VEGF) and transcription factors (as NFE2L2, MAFF, HES1, FOSL1, TGIF1) relevant for cardiovascular and lung disease. By means of network reconstruction, four genes (STAT3, HIF1a, NFKB1, KRAS) have emerged as major regulators of transcriptional response of bronchial epithelial cells exposed to diesel exhaust.

CONCLUSIONS: Overall, this work highlights modifications of the transcriptional landscape in human bronchial cells exposed to UFP and sheds new lights on possible mechanisms by means of which UFP acts as a carcinogen and harmful factor for human health.}, } @article {pmid29703137, year = {2018}, author = {Die, JV and Gil, J and Millan, T}, title = {Genome-wide identification of the auxin response factor gene family in Cicer arietinum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {301}, pmid = {29703137}, issn = {1471-2164}, support = {INIA RTA2013-00025//Instituto Nacional de Investigación y Tecnología Agraria y Alimentaria/ ; }, mesh = {Cicer/*genetics/growth & development ; Gene Duplication ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Genome, Plant ; Indoleacetic Acids/*metabolism ; *Multigene Family ; Phylogeny ; Plant Proteins/*genetics ; }, abstract = {BACKGROUND: Auxin Response Factors act as critical components of the auxin-signaling pathway by regulating the transcription of auxin-responsive genes. The release of the chickpea reference genome provides an opportunity to identify and characterize the ARF gene family in this important legume by a data mining coupled by comparative genomics approaches.

RESULTS: We performed a comprehensive characterization and analysis of 24 ARF genes in the chickpea reference genome. Comparative phylogenetic analysis of the ARF from chickpea, Medicago and Arabidopsis suggests that recent duplications have played a very limited role in the expansion of the ARF chickpea family. Gene structure analysis based on exon-intron organization provides additional evidence to support the evolutionary relationship among the ARF members. Conserved motif analysis shows that most of the proteins fit into the canonical ARF structure model, but 9 proteins lack or have a truncated dimerization domain. The mechanisms underlying the diversification of the ARF gene family are based on duplications, variations in domain organization and alternative splicing. Concerning duplications, segmental, but not tandem duplications, have contributed to the expansion of the gene family. Moreover, the duplicated pair genes have evolved mainly under the influence of purifying selection pressure with restricted functional divergence. Expression profiles responding to various environmental stimuli show a close relationship between tissue and expression patterns. Promoter sequence analysis reveals an enrichment of several cis-regulatory elements related to symbiosis, and modulation of plant gene expression during the interaction with microbes.

CONCLUSIONS: In conclusion, this study provides a comprehensive overview of the ARF gene family in chickpea. Globally, our data supports that auxin signaling pathway regulates a wide range of physiological processes and stress responses. Our findings could further provide new insights into the complexity of the regulation of ARF at the transcription level that may be useful to develop rational chickpea breeding strategies to improve development or stress responses. Our study also provides a foundation for comparative genomic analyses and a framework to trace the dynamic evolution of ARF genes on a large time-scale within the legume family.}, } @article {pmid29703136, year = {2018}, author = {Choque, E and Klopp, C and Valiere, S and Raynal, J and Mathieu, F}, title = {Whole-genome sequencing of Aspergillus tubingensis G131 and overview of its secondary metabolism potential.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {200}, doi = {10.1186/s12864-018-4574-4}, pmid = {29703136}, issn = {1471-2164}, mesh = {Aspergillus/classification/*genetics/isolation & purification ; Farms ; Fungal Proteins/genetics ; Genome Size ; Indoles/metabolism ; Molecular Sequence Annotation ; Phylogeny ; Piperazines/metabolism ; *Secondary Metabolism ; Whole Genome Sequencing/*methods ; }, abstract = {BACKGROUND: Black Aspergilli represent one of the most important fungal resources of primary and secondary metabolites for biotechnological industry. Having several black Aspergilli sequenced genomes should allow targeting the production of certain metabolites with bioactive properties.

RESULTS: In this study, we report the draft genome of a black Aspergilli, A. tubingensis G131, isolated from a French Mediterranean vineyard. This 35 Mb genome includes 10,994 predicted genes. A genomic-based discovery identifies 80 secondary metabolites biosynthetic gene clusters. Genomic sequences of these clusters were blasted on 3 chosen black Aspergilli genomes: A. tubingensis CBS 134.48, A. niger CBS 513.88 and A. kawachii IFO 4308. This comparison highlights different levels of clusters conservation between the four strains. It also allows identifying seven unique clusters in A. tubingensis G131. Moreover, the putative secondary metabolites clusters for asperazine and naphtho-gamma-pyrones production were proposed based on this genomic analysis. Key biosynthetic genes required for the production of 2 mycotoxins, ochratoxin A and fumonisin, are absent from this draft genome. Even if intergenic sequences of these mycotoxins biosynthetic pathways are present, this could not lead to the production of those mycotoxins by A. tubingensis G131.

CONCLUSIONS: Functional and bioinformatics analyses of A. tubingensis G131 genome highlight its potential for metabolites production in particular for TAN-1612, asperazine and naphtho-gamma-pyrones presenting antioxidant, anticancer or antibiotic properties.}, } @article {pmid29703134, year = {2018}, author = {Silva, GS and Souza, MM and de Melo, CAF and Urdampilleta, JD and Forni-Martins, ER}, title = {Identification and characterization of karyotype in Passiflora hybrids using FISH and GISH.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {26}, pmid = {29703134}, issn = {1471-2156}, support = {Financial Support//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; Financial Support//Fundação de Amparo à Pesquisa do Estado da Bahia (BR)/ ; Financial Support and Grant//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; Financial Support//Universidade Estadual de Santa Cruz/ ; }, abstract = {BACKGROUND: A great interest exists in the production of hybrid plants of the genus Passiflora given the beauty and exotic features of its flowers which have ornamental value. Hybrid paternity confirmation is therefore important for assuring germplasm origin, and is typically carried out by molecular marker segregation. The aim of this study was to karyotypically characterize the chromosome heritance patterns of the progeny resultant from a cross of P. gardneri and P. gibertii using classical cytogenetics, chromosome banding, and molecular cytogenetics.

RESULTS: All analyzed genotypes showed the same diploid chromosome number as the genitor species: 2n = 18. Classical and CMA3 and DAPI staining allowed for chromosome counting and satellite identification (secondary constrictions). Fluorescence in situ hybridization (FISH) and genomic in situ hybridization (GISH) were used to characterize subgenomes by either identifying rDNA-specific genome patterns or parental genomes, respectively.

CONCLUSIONS: The heritance of chromosomal markers presenting rDNA sites from each parent for genome identification confirmed that all obtained plants were hybrids. These results will improve breeding programs involving the species of this genus. Apart from confirming hybridization, GISH allowed the visualization of recombination between the homeologous chromosome and the introgression of sequences of interest.}, } @article {pmid29703133, year = {2018}, author = {Herbert, ZT and Kershner, JP and Butty, VL and Thimmapuram, J and Choudhari, S and Alekseyev, YO and Fan, J and Podnar, JW and Wilcox, E and Gipson, J and Gillaspy, A and Jepsen, K and BonDurant, SS and Morris, K and Berkeley, M and LeClerc, A and Simpson, SD and Sommerville, G and Grimmett, L and Adams, M and Levine, SS}, title = {Cross-site comparison of ribosomal depletion kits for Illumina RNAseq library construction.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {199}, doi = {10.1186/s12864-018-4585-1}, pmid = {29703133}, issn = {1471-2164}, support = {P30 ES002109/ES/NIEHS NIH HHS/United States ; P30-CA14051//National Cancer Institute/ ; P30-ES002109//National Institute of Environmental Health Sciences/ ; P30 AI060354//Harvard University Center for AIDS Research (US)/ ; }, mesh = {Gene Expression Profiling/methods ; Gene Library ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Poly A/genetics ; RNA, Ribosomal/genetics/*isolation & purification ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Ribosomal RNA (rRNA) comprises at least 90% of total RNA extracted from mammalian tissue or cell line samples. Informative transcriptional profiling using massively parallel sequencing technologies requires either enrichment of mature poly-adenylated transcripts or targeted depletion of the rRNA fraction. The latter method is of particular interest because it is compatible with degraded samples such as those extracted from FFPE and also captures transcripts that are not poly-adenylated such as some non-coding RNAs. Here we provide a cross-site study that evaluates the performance of ribosomal RNA removal kits from Illumina, Takara/Clontech, Kapa Biosystems, Lexogen, New England Biolabs and Qiagen on intact and degraded RNA samples.

RESULTS: We find that all of the kits are capable of performing significant ribosomal depletion, though there are differences in their ease of use. All kits were able to remove ribosomal RNA to below 20% with intact RNA and identify ~ 14,000 protein coding genes from the Universal Human Reference RNA sample at >1FPKM. Analysis of differentially detected genes between kits suggests that transcript length may be a key factor in library production efficiency.

CONCLUSIONS: These results provide a roadmap for labs on the strengths of each of these methods and how best to utilize them.}, } @article {pmid29703132, year = {2018}, author = {Gayk, ZG and Le Duc, D and Horn, J and Lindsay, AR}, title = {Genomic insights into natural selection in the common loon (Gavia immer): evidence for aquatic adaptation.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {64}, pmid = {29703132}, issn = {1471-2148}, mesh = {Adaptation, Physiological/*genetics ; Animals ; Base Composition/genetics ; Biological Evolution ; Birds/*genetics ; Female ; *Genome ; Phylogeny ; *Selection, Genetic ; *Water ; }, abstract = {BACKGROUND: The common loon (Gavia immer) is one of five species that comprise the avian order Gaviiformes. Loons are specialized divers, reaching depths up to 60 m while staying submerged for intervals up to three minutes. In this study we used comparative genomics to investigate the genetic basis of the common loon adaptations to its ecological niche. We used Illumina short read DNA sequence data from a female bird to produce a draft assembly of the common loon (Gavia immer) genome.

RESULTS: We identified 14,169 common loon genes, which based on well-resolved avian genomes, represent approximately 80.7% of common loon genes. Evolutionary analyses between common loon and Adelie penguin (Pygoscelis adeliae), red-throated loon (Gavia stellata), chicken (Gallus gallus), northern fulmar (Fulmarus glacialis), and rock pigeon (Columba livia) show 164 positively selected genes in common and red-throated loons. These genes were enriched for a number of protein classes, including those involved in muscle tissue development, immunoglobulin function, hemoglobin iron binding, G-protein coupled receptors, and ATP metabolism.

CONCLUSIONS: Signatures of positive selection in these areas suggest the genus Gavia may have adapted for underwater diving by modulating their oxidative and metabolic pathways. While more research is required, these adaptations likely result in (1) compensations in oxygen respiration and energetic metabolism, (2) low-light visual acuity, and (3) elevated solute exchange. This work represents the first effort to understand the genomic adaptations of the common loon as well as other Gavia and may have implications for subsequent studies that target particular genes for loon population genetic, ecological or conservation studies.}, } @article {pmid29703131, year = {2018}, author = {Arafat, H and Alamaru, A and Gissi, C and Huchon, D}, title = {Extensive mitochondrial gene rearrangements in Ctenophora: insights from benthic Platyctenida.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {65}, pmid = {29703131}, issn = {1471-2148}, support = {161/15//Israel Science Foundation/International ; }, mesh = {Animals ; Biological Evolution ; Conserved Sequence/genetics ; Ctenophora/*genetics ; DNA, Mitochondrial/genetics ; Gene Order ; *Gene Rearrangement ; *Genes, Mitochondrial ; Genome, Mitochondrial ; Mitochondria/genetics ; Molecular Sequence Annotation ; Open Reading Frames/genetics ; Phylogeny ; RNA, Ribosomal/genetics ; }, abstract = {BACKGROUND: Complete mitochondrial (mt) genomes have been sequenced for thousands of animals and represent a molecule of choice for many evolutionary studies. Nevertheless, some animal groups have remained under-sampled. Ctenophora (comb jellies) is one such example, with only two complete mt sequences determined hitherto for this phylum, which encompasses ca. 150-200 described species. This lack of data derives from the extremely fast mt evolutionary rate in this lineage, complicating primer design and DNA amplification. Indeed, in the two ctenophore mt genomes sequenced to date, i.e. those of Mnemiopsis leidyi (order Lobata) and Pleurobrachia bachei (order Cydippida), both rRNA and protein coding genes exhibit an extraordinary size reduction and have highly derived sequences. Additionally, all tRNAs, and the atp6 and atp8 genes are absent. In order to determine whether these characteristics are shared by other ctenophores, we obtained the complete mt genomes of three benthic ctenophores belonging to the so far unsampled order of Platyctenida: Coeloplana loyai, Coeloplana yulianicorum and Vallicula multiformis.

RESULTS: The mt genomes of benthic ctenophores reveal the same peculiarities found in Mnemiopsis and Pleurobrachia, demonstrating that the fast evolutionary rate is a general trait of the ctenophore mt genomes. Our results also indicate that this high evolutionary rate not only affects the nucleotide substitution but also gene rearrangements. Indeed, gene order was highly rearranged among representatives of the different taxonomic orders in which it was close to random, but also quite variable within Platyctenida, in which the genera Coeloplana and Vallicula share only four conserved synteny blocks. However, the two congeneric Coeloplana species display exactly the same gene order. Because of the extreme evolutionary rate, our phylogenetic analyses were unable to resolve the phylogenetic position of ctenophores within metazoans or the relationships among the different Ctenophora orders. Comparative sequence-analyses allowed us to correct the annotation of the Pleurobrachia mt genome, confirming the absence of tRNAs, the presence of both rRNA genes, and the existence of a reassignment of codon TGA from tryptophan to serine for this species.

CONCLUSIONS: Since Platyctenida is an early diverging lineage among Ctenophora, our findings suggest that the mt traits described above are ancestral characteristics of this phylum.}, } @article {pmid29703130, year = {2018}, author = {Wang, W and Su, X and Tian, Z and Liu, Y and Zhou, Y and He, M}, title = {Transcriptome profiling provides insights into dormancy release during cold storage of Lilium pumilum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {196}, doi = {10.1186/s12864-018-4536-x}, pmid = {29703130}, issn = {1471-2164}, support = {31470698//National Natural Science Foundation of China/ ; }, mesh = {Cold Temperature ; Epigenesis, Genetic ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; Lilium/*genetics/ultrastructure ; Phenotype ; Plant Dormancy/*genetics ; Plant Proteins/genetics ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Bulbs of the ornamental flower Lilium pumilum enter a period of dormancy after flowering in spring, and require exposure to cold for a period of time in order to release dormancy. Previous studies focused mainly on anatomical, physiological and biochemical changes during dormancy release. There are no dormancy studies of the northern cold-hardy wild species of Lilium at the molecular level. This study observed bulb cell and starch granule ultrastructures during cold storage; and analysed the transcriptome using sequencing. The combination of morphological and transcriptomic methods provides valuable insights into dormancy release during cold storage of Lilium pumilum.

RESULTS: Ultrastructural changes reflected dormancy release during cold storage of the bulbs. We compared gene expression levels among samples at 0 (S1 stage), 30 (S2 stage), 60 (S3 stage) and 90 (S4 stage) d of cold storage, with 0 d as the control. The data showed that some regulatory pathways such as carbohydrate metabolism and plant hormone signal transduction were activated to break dormancy. Some differentially expressed genes (DEGs) related to antioxidant activity, epigenetic modification and transcription factors were induced to respond to low temperature conditions. These genes constituted a complex regulatory mechanism of dormancy release.

CONCLUSIONS: Cytological data related to dormancy regulation was obtained through histomorphological observation; transcriptome sequencing provided comprehensive sequences and digital gene expression tag profiling (DGE) data, and bulb cell ultrastructural changes were closely related to DEGs. The novel Lilium pumilum genetic information from this study provides a reference for the regulation of dormancy by genetic engineering using molecular biology tools.}, } @article {pmid29702423, year = {2018}, author = {Netzker, T and Flak, M and Krespach, MK and Stroe, MC and Weber, J and Schroeckh, V and Brakhage, AA}, title = {Microbial interactions trigger the production of antibiotics.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {117-123}, doi = {10.1016/j.mib.2018.04.002}, pmid = {29702423}, issn = {1879-0364}, abstract = {Since the discovery of penicillin, antibiotics have been instrumental in treating infectious diseases. However, emerging antibiotic multi-resistance coinciding with a nearly exhausted drug pipeline is a major concern for the future of the therapy of infections. A novel approach for the discovery of antibiotics relies on the analysis of microbial consortia in their ecological context, taking into account the potential natural role of antibiotics. Co-cultivations of microorganisms have been successfully applied for the isolation of unknown secondary metabolites including antibiotics, and, thus, open new avenues to the production of bioactive compounds while at the same time providing insight into the natural function of the produced molecules and the regulation of their formation.}, } @article {pmid29702349, year = {2018}, author = {Briegel, A and Uphoff, S}, title = {Editorial overview: The new microscopy.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {208-211}, doi = {10.1016/j.mib.2018.04.003}, pmid = {29702349}, issn = {1879-0364}, mesh = {Humans ; Microscopy/*instrumentation/*methods ; }, } @article {pmid29702219, year = {2018}, author = {Dnyansagar, R and Zimmermann, B and Moran, Y and Praher, D and Sundberg, P and Møller, LF and Technau, U}, title = {Dispersal and speciation: The cross Atlantic relationship of two parasitic cnidarians.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {346-355}, doi = {10.1016/j.ympev.2018.04.035}, pmid = {29702219}, issn = {1095-9513}, mesh = {Animal Migration/*physiology ; Animals ; Atlantic Ocean ; Base Sequence ; Cnidaria/*genetics ; Evolution, Molecular ; *Genetic Speciation ; Genome ; Parasites/*genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; RNA, Ribosomal, 18S/genetics ; Reproductive Isolation ; Transcriptome/genetics ; Wnt Signaling Pathway/genetics ; }, } @article {pmid29702218, year = {2018}, author = {Mikkelsen, NT and Kocot, KM and Halanych, KM}, title = {Mitogenomics reveals phylogenetic relationships of caudofoveate aplacophoran molluscs.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {429-436}, doi = {10.1016/j.ympev.2018.04.031}, pmid = {29702218}, issn = {1095-9513}, abstract = {The worm-shaped, shell-less aplacophoran molluscs Caudofoveata and Solenogastres have recently received attention as part of the clade Aculifera, but relationships within these two lineages are still largely unknown. Here, we use complete mitochondrial genomes to shed light on higher-level relationships within Caudofoveata. Mitochondrial genomes have been sequenced for many diverse molluscs, but only two mitochondrial genomes from aplacophoran molluscs (the caudofoveates Scutopus ventrolineatus and Chaetoderma nitidulum) are available to date. We sequenced and assembled complete or near complete mitochondrial genomes of five additional species of Caudofoveata (Falcidens acutargatus, Falcidens halanychi, Scutopus robustus, Psilodens balduri and Spathoderma clenchi) and one species of Solenogastres (Neomenia carinata) for comparison to available mitochondrial genomes of aculiferans. Comparison of mitochondrial gene order among different lineages revealed a highly conserved order of protein coding genes corresponding to the hypothesized ancestral gene order for Mollusca. Unique arrangements of tRNAs were found among lineages of aculiferan molluscs as well as among caudofoveate taxa. Phylogenetic analyses of amino acid sequences for the 13 protein-coding genes recovered a monophyletic Aplacophora. Within Caudofoveata, Chaetodermatidae, but not Limifossoridae, was recovered monophyletic. Taken together, our results suggest that mitochondrial genomes can serve as useful molecular markers for aculiferan phylogenetics, especially for more recent phylogenetic events.}, } @article {pmid29702217, year = {2018}, author = {Dong, W and Xu, C and Wu, P and Cheng, T and Yu, J and Zhou, S and Hong, DY}, title = {Resolving the systematic positions of enigmatic taxa: Manipulating the chloroplast genome data of Saxifragales.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {321-330}, doi = {10.1016/j.ympev.2018.04.033}, pmid = {29702217}, issn = {1095-9513}, mesh = {Bayes Theorem ; *Genome, Chloroplast ; Likelihood Functions ; *Phylogeny ; Saxifragales/*classification/*genetics ; Trees/classification/genetics ; }, abstract = {Accurately resolving the phylogeny of enigmatic taxa is always a challenge in phylogenetic inference. Such uncertainties could be due to systematic errors or model violations. Here, we provide an example demonstrating how these factors affect the positioning of Paeoniaceae within Saxifragales based on chloroplast genome data. We newly assembled 14 chloroplast genomes from Saxifragales, and by combining these genomes with those of 63 other angiosperms, three datasets were assembled to test different hypotheses proposed by recent studies. These datasets were subjected to maximum parsimony, maximum likelihood and Bayesian analyses with site-homogeneous/heterogeneous models, different data partitioning strategies, and the inclusion/exclusion of weak phylogenetic signals. Three datasets exhibited remarkable heterogeneity among sites and among taxa of Saxifragales. Phylogenetic analyses under homogeneous models or maximum parsimony showed a closer relationship of Paeoniaceae with herbaceous families in the order. Data partitioning strategies did not change the general tree topology. However, PhyloBayes analysis under the CAT+GTR model resulted in a relationship closer to woody families. We conclude that although genomic data significantly increase the phylogenetic resolution of enigmatic taxa with high support, the phylogenetic results inferred from such data might be analysis or signal dependent. The analytical pipeline outlined here combines phylogenomic inference methods with evaluation of lineage-specific rates of substitution, model selection, and assessment of systematic error. These methods would be applicable to resolve similar difficult questions in the tree of life.}, } @article {pmid29702216, year = {2018}, author = {Zúñiga-Reinoso, Á and Méndez, MA}, title = {Hidden and cryptic species reflect parallel and correlated evolution in the phylogeny of the genus Callyntra (Coleoptera: Tenebrionidae) of Central Chile.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {405-415}, doi = {10.1016/j.ympev.2018.04.022}, pmid = {29702216}, issn = {1095-9513}, abstract = {The origin of cryptic species has traditionally been associated with events of recent speciation, genetic constraints, selection of an adaptive character, sexual selection and/or convergent evolution. Species of the genus Callyntra inhabit coastal terraces, mountain slopes, and peaks; their elytral designs are associated with each of these habitats. However, cryptic species have been described within each of these habitats; the taxonomy of this group has been problematic, thus establishing the phylogenetic relationships in this group is fundamental to clarify the systematics and evolutionary patterns of Callyntra. We reconstructed the phylogeny of this group using two mitochondrial genes (COI, 16S) and one nuclear gene (Mp20). We also performed species delimitation using PTP based methods (PTP, mlPTP, bPTP) and GMYC, and evaluated the evolution of the elytral design related to habitat preference. The results showed a tree with five clades, that together with the different methods of species delimitation recovered the described species and suggested at least five new species. The elytral design and habitat preference showed phylogenetic signals. We propose a new classification based on monophyletic groups recovered by phylogenetic analyses. We also suggest that parallel evolution in different habitats and later stasis in the elytral design would be the cause of the origin of cryptic species in this group from central Chile.}, } @article {pmid29702215, year = {2018}, author = {Gamboa-Tuz, SD and Pereira-Santana, A and Zhao, T and Schranz, ME and Castano, E and Rodriguez-Zapata, LC}, title = {New insights into the phylogeny of the TMBIM superfamily across the tree of life: Comparative genomics and synteny networks reveal independent evolution of the BI and LFG families in plants.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {266-278}, doi = {10.1016/j.ympev.2018.04.032}, pmid = {29702215}, issn = {1095-9513}, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Archaea/metabolism ; Bacteria/metabolism ; Bryophyta/metabolism ; Calcium Channels/metabolism ; Conserved Sequence/genetics ; Eukaryota/metabolism ; *Evolution, Molecular ; *Genomics ; Hydrogen-Ion Concentration ; *Multigene Family ; *Phylogeny ; Plant Proteins/chemistry/*genetics ; Plants/*genetics ; Synteny/*genetics ; }, abstract = {The Transmembrane BAX Inhibitor Motif containing (TMBIM) superfamily, divided into BAX Inhibitor (BI) and Lifeguard (LFG) families, comprises a group of cytoprotective cell death regulators conserved in prokaryotes and eukaryotes. However, no research has focused on the evolution of this superfamily in plants. We identified 685 TMBIM proteins in 171 organisms from Archaea, Bacteria, and Eukarya, and provided a phylogenetic overview of the whole TMBIM superfamily. Then, we used orthology and synteny network analyses to further investigate the evolution and expansion of the BI and LFG families in 48 plants from diverse taxa. Plant BI family forms a single monophyletic group; however, monocot BI sequences transposed to another genomic context during evolution. Plant LFG family, which expanded trough whole genome and tandem duplications, is subdivided in LFG I, LFG IIA, and LFG IIB major phylogenetic groups, and retains synteny in angiosperms. Moreover, two orthologous groups (OGs) are shared between bryophytes and seed plants. Other several lineage-specific OGs are present in plants. This work clarifies the phylogenetic classification of the TMBIM superfamily across the three domains of life. Furthermore, it sheds new light on the evolution of the BI and LFG families in plants providing a benchmark for future research.}, } @article {pmid29702214, year = {2018}, author = {Spalink, D and Stoffel, K and Walden, GK and Hulse-Kemp, AM and Hill, TA and Van Deynze, A and Bohs, L}, title = {Comparative transcriptomics and genomic patterns of discordance in Capsiceae (Solanaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {293-302}, doi = {10.1016/j.ympev.2018.04.030}, pmid = {29702214}, issn = {1095-9513}, mesh = {Chromosomes, Plant/genetics ; Evolution, Molecular ; Flowers/genetics ; *Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Ontology ; *Genomics ; Molecular Sequence Annotation ; Phylogeny ; Solanaceae/*genetics ; Transcriptome/genetics ; }, abstract = {The integration of genomics and phylogenetics allows new insight into the structure of gene tree discordance, the relationships among gene position, gene history, and rate of evolution, as well as the correspondence of gene function, positive selection, and gene ontology enrichment across lineages. We explore these issues using the tribe Capsiceae (Solanaceae), which is comprised of the genera Lycianthes and Capsicum (peppers). In combining the annotated genomes of Capsicum with newly sequenced transcriptomes of four species of Lycianthes and Capsicum, we develop phylogenies for 6747 genes, and construct a backbone species tree using both concordance and explicit phylogenetic network approaches. We quantify phylogenetic discordance among individual gene trees, measure their rates of synonymous and nonsynonymous substitution, and test whether they were positively selected along any branch of the phylogeny. We then map these genes onto the annotated Capsicum genome and test whether rates of evolution, gene history, and gene ontology vary significantly with gene position. We observed substantial discordance among gene trees. A bifurcating species tree placing Capsicum within a paraphyletic Lycianthes was supported over all phylogenetic networks. Rates of synonymous and nonsynonymous substitution varied 41-fold and 130-fold among genes, respectively, and were significantly lower in pericentromeric regions. We found that results of concordance tree analyses vary depending on the subset of genes used, and that genes within the pericentromeric regions only capture a portion of the observed discordance. We identified 787 genes that have been positively selected throughout the diversification history of Capsiceae, and discuss the importance of these genes as targets for investigation of economically important traits in the domesticated peppers.}, } @article {pmid29702213, year = {2018}, author = {Schley, RJ and de la Estrella, M and Pérez-Escobar, OA and Bruneau, A and Barraclough, T and Forest, F and Klitgård, B}, title = {Is Amazonia a 'museum' for Neotropical trees? The evolution of the Brownea clade (Detarioideae, Leguminosae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {279-292}, doi = {10.1016/j.ympev.2018.04.029}, pmid = {29702213}, issn = {1095-9513}, mesh = {Biodiversity ; *Biological Evolution ; Calibration ; Fabaceae/*classification ; Fossils ; Phylogeny ; Phylogeography ; South America ; Time Factors ; Trees/*classification ; *Tropical Climate ; }, abstract = {The flora of the Neotropics is unmatched in its diversity, however the mechanisms by which diversity has accumulated are debated and largely unclear. The Brownea clade (Leguminosae) is a characteristic component of the Neotropical flora, and the species within it are diverse in their floral morphology, attracting a wide variety of pollinators. This investigation aimed to estimate species divergence times and infer relationships within the group, in order to test whether the Brownea clade followed the 'cradle' or 'museum' model of diversification, i.e. whether species evolved rapidly over a short time period, or gradually over many millions of years. We also aimed to trace the spatio-temporal evolution of the clade by estimating ancestral biogeographical patterns in the group. We used BEAST to build a dated phylogeny of 73 Brownea clade species using three molecular markers (ITS, trnK and psbA-trnH), resulting in well-resolved phylogenetic relationships within the clade, as well as robust divergence time estimates from which we inferred diversification rates and ancestral biogeography. Our analyses revealed an Eocene origin for the group, after which the majority of diversification happened in Amazonia during the Miocene, most likely concurrent with climatic and geological changes caused by the rise of the Andes. We found no shifts in diversification rate over time, suggesting a gradual accumulation of lineages with low extinction rates. These results may help to understand why Amazonia is host to the highest diversity of tree species on Earth.}, } @article {pmid29701882, year = {2018}, author = {Fossen, EIF and Pélabon, C and Einum, S}, title = {An empirical test for a zone of canalization in thermal reaction norms.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {936-943}, doi = {10.1111/jeb.13287}, pmid = {29701882}, issn = {1420-9101}, abstract = {Theoretical models on the evolution of phenotypic plasticity predict a zone of canalization where reaction norms cross, and genetic variation is minimized in the environment a population most frequently encounter. Empirical tests of this prediction are largely missing, in particular for life-history traits. We addressed this prediction by quantifying thermal reaction norms of three life-history traits (somatic growth rate, age and size at maturation) of a Norwegian population of Daphnia magna and testing for the occurrence of an intermediate temperature (Tm) at which genetic variance in the traits is minimized. Size at maturation changed relatively little with temperature compared to the other traits, and there was no genetic variance in the shape of the reaction norm. Consequently, age at maturation and somatic growth rate were strongly negatively correlated. Both traits showed a strong genotype-environment interaction, and the estimated Tm was 14 °C for both age at maturation and growth rate. This value of Tm corresponds well with mean summer temperatures experienced by the population and suggests that the population has evolved under stabilizing selection in temperatures that fluctuate around this mean temperature. These results suggest local adaptation to temperature in the studied population and allow predicting evolutionary trajectories of thermal reaction norms under changing thermal regimes.}, } @article {pmid29701800, year = {2018}, author = {Savory, FR and Milner, DS and Miles, DC and Richards, TA}, title = {Ancestral Function and Diversification of a Horizontally Acquired Oomycete Carboxylic Acid Transporter.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1887-1900}, pmid = {29701800}, issn = {1537-1719}, abstract = {Horizontal gene transfer (HGT) can equip organisms with novel genes, expanding the repertoire of genetic material available for evolutionary innovation and allowing recipient lineages to colonize new environments. However, few studies have characterized the functions of HGT genes experimentally or examined postacquisition functional divergence. Here, we report the use of ancestral sequence reconstruction and heterologous expression in Saccharomyces cerevisiae to examine the evolutionary history of an oomycete transporter gene family that was horizontally acquired from fungi. We demonstrate that the inferred ancestral oomycete HGT transporter proteins and their extant descendants transport dicarboxylic acids which are intermediates of the tricarboxylic acid cycle. The substrate specificity profile of the most ancestral protein has largely been retained throughout the radiation of oomycetes, including in both plant and animal pathogens and in a free-living saprotroph, indicating that the ancestral HGT transporter function has been maintained by selection across a range of different lifestyles. No evidence of neofunctionalization in terms of substrate specificity was detected for different HGT transporter paralogues which have different patterns of temporal expression. However, a striking expansion of substrate range was observed for one plant pathogenic oomycete, with a HGT derived paralogue from Pythium aphanidermatum encoding a protein that enables tricarboxylic acid uptake in addition to dicarboxylic acid uptake. This demonstrates that HGT acquisitions can provide functional additions to the recipient proteome as well as the foundation material for the evolution of expanded protein functions.}, } @article {pmid29701793, year = {2018}, author = {Dennert, F and Imperiali, N and Staub, C and Schneider, J and Laessle, T and Zhang, T and Wittwer, R and van der Heijden, MGA and Smits, THM and Schlaeppi, K and Keel, C and Maurhofer, M}, title = {Conservation tillage and organic farming induce minor variations in Pseudomonas abundance, their antimicrobial function and soil disease resistance.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {8}, pages = {}, doi = {10.1093/femsec/fiy075}, pmid = {29701793}, issn = {1574-6941}, abstract = {Conservation tillage and organic farming are strategies used worldwide to preserve the stability and fertility of soils. While positive effects on soil structure have been extensively reported, the effects on specific root- and soil-associated microorganisms are less known. The aim of this study was to investigate how conservation tillage and organic farming influence the frequency and activity of plant-beneficial pseudomonads. Amplicon sequencing using the 16S rRNA gene revealed that Pseudomonas is among the most abundant bacterial taxa in the root microbiome of field-grown wheat, independent of agronomical practices. However, pseudomonads carrying genes required for the biosynthesis of specific antimicrobial compounds were enriched in samples from conventionally farmed plots without tillage. In contrast, disease resistance tests indicated that soil from conventional no tillage plots is less resistant to the soilborne pathogen Pythium ultimum compared to soil from organic reduced tillage plots, which exhibited the highest resistance of all compared cropping systems. Reporter strain-based gene expression assays did not reveal any differences in Pseudomonas antimicrobial gene expression between soils from different cropping systems. Our results suggest that plant-beneficial pseudomonads can be favoured by certain soil cropping systems, but soil resistance against plant diseases is likely determined by a multitude of biotic factors in addition to Pseudomonas.}, } @article {pmid29701776, year = {2018}, author = {Karimi, E and Slaby, BM and Soares, AR and Blom, J and Hentschel, U and Costa, R}, title = {Metagenomic binning reveals versatile nutrient cycling and distinct adaptive features in alphaproteobacterial symbionts of marine sponges.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy074}, pmid = {29701776}, issn = {1574-6941}, abstract = {Marine sponges are early-branched metazoans known to harbor dense and diverse microbial communities. Yet the role of the so far uncultivable alphaproteobacterial lineages that populate these sessile invertebrates remains unclear. We applied a sequence composition-dependent binning approach to assemble one Rhodospirillaceae genome from the Spongia officinalis microbial metagenome and contrast its functional features with those of closely related sponge-associated and free-living genomes. Both symbiotic and free-living Rhodospirillaceae shared a suite of common features, possessing versatile carbon, nitrogen, sulfur and phosphorus metabolisms. Symbiotic genomes could be distinguished from their free-living counterparts by the lack of chemotaxis and motility traits, enrichment of genes required for the uptake and utilization of organic sulfur compounds-particularly taurine-, higher diversity and abundance of ABC transporters, and a distinct repertoire of genes involved in natural product biosynthesis, plasmid stability, cell detoxification and oxidative stress remediation. These sessile symbionts may more effectively contribute to host fitness via nutrient exchange, and also host detoxification and chemical defense. Considering the worldwide occurrence and high diversity of sponge-associated Rhodospirillaceae verified here using a tailored in silico approach, we suggest that these organisms are not only relevant to holobiont homeostasis but also to nutrient cycling in benthic ecosystems.}, } @article {pmid29701577, year = {2018}, author = {Yoon, J and Kang, DH}, title = {Terasakiella salincola sp. nov., a marine alphaproteobacterium isolated from seawater, and emended description of the genus Terasakiella.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2048-2053}, doi = {10.1099/ijsem.0.002788}, pmid = {29701577}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hydroxybutyrates ; Methylocystaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Polyesters ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-reaction-negative, S-shaped, motile, poly-β-hydroxybutyrate-accumulating, facultatively anaerobic, beige-pigmented bacterium, designated strain KMU-80T, was isolated from seawater collected from the Republic of Korea. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the novel isolate was affiliated with the family Methylocystaceae, of the class Alphaproteobacteria, and that it possessed the greatest sequence similarity (96.7 %) to Terasakiella pusilla NBRC 13613T. The DNA G+C content of KMU-80T was 48.3 mol%, and ubiquinone 10 was the sole respiratory quinone. The predominant cellular fatty acids consisted of C18 : 1ω7c (60.2 %), C16 : 0 (13.4 %) and C16 : 1ω7c and/or C16 : 1ω6c (11.1 %). Strain KMU-80T had phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, an unidentified aminolipid, an unidentified phospholipid and four unidentified lipids as polar lipids. Based on its distinct phylogenetic position and the combination of genotypic and phenotypic characteristics, this strain is considered to represent a novel species of the genus Terasakiella, for which the name Terasakiella salincola sp. nov. is proposed. The type strain of T. salincola sp. nov. is KMU-80T (= KCCM 90274T = NBRC 112846T). An amended description of the genus Terasakiella is also provided.}, } @article {pmid29701576, year = {2018}, author = {Yu, XY and Yu, XD and Fu, GY and Zhao, Z and Shen, X and Sun, C and Wu, M}, title = {Marinicaulis flavus gen. nov., sp. nov., a novel stalked bacterium of the family Parvularculaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2061-2067}, doi = {10.1099/ijsem.0.002795}, pmid = {29701576}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, ovoid or short rod-shaped bacterium with prosthecates and flagella, designated SY-3-19T, was isolated from the surface seawater of the South China Sea, and subjected to a polyphasic taxonomic study. The isolate grew at 4-40 °C and pH 5.0-9.0 (optimum 28 °C and pH 6.5-7.5), and with 0.5-16.0 % (w/v) NaCl (optimum 4 %). It was positive for oxidase and catalase activity. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain SY-3-19T constituted a separate branch in the family Parvularculaceae, sharing the highest sequence similarities to the genera Aquisalinus (91.9 %), Amphiplicatus (91.1 %) and Parvularcula(91.0-89.4 %). The sole respiratory quinone was ubiquinone-10 and the principal fatty acids (>10 %) were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), 11 methyl C18 : 1ω7c and C16 : 0. The polar lipids of strain SY-3-19T consisted of phosphatidylglycerol, nine unidentified glycolipids and four unidentified lipids. The DNA G+C content was 60.9 mol%. On the basis of morphological, physiological and chemotaxonomic characteristics, together with the results of phylogenetic analysis, strain SY-3-19T is described as a novel species in a novel genus, for which the name Marinicaulis flavus gen. nov., sp. nov. (type strain SY-3-19T=MCCC 1K03432T=KCTC 62156T) is proposed.}, } @article {pmid29701575, year = {2018}, author = {Zhao, ZL and Ming, H and Ji, WL and Khieu, TN and Chu-Ky, S and Cheng, LJ and Meng, XL and Li, WJ and Nie, GX}, title = {Paenibacillus esterisolvens sp. nov., isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {7}, pages = {2145-2150}, doi = {10.1099/ijsem.0.002754}, pmid = {29701575}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Genes, Bacterial ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vietnam ; }, abstract = {A Gram-stain-positive, aerobic, motile with peritrichous flagella, rod-shaped bacterium, designated CFH S0170T, was isolated from a soil sample collected from Catba island in Ha Long Bay, Hai Phong City, Vietnam. Comparison of the 16S rRNA gene sequences showed that strain CFH S0170T belonged to the genus Paenibacillus and showed closest relationship with Paenibacillus vulneris CCUG 53270T (98.1 % similarity). Phylogenetic analysis demonstrated that the novel candidate formed a coherent branch with P. vulneris CCUG 53270T and Paenibacillus yunnanensis YN2T. Furthermore, the novel strain shared 87.2 % rpoB gene sequence similarity with P. vulneris CCUG 53270T. Growth of strain CFH S0170T occurred at 10-40 °C, pH 6.0-8.0 and with 0-2.0 % (w/v) NaCl. Strain CFH S0170T contained mannose, glucose and rhamnose as the major whole-cell sugars. The cell-wall peptidoglycan contained meso-diaminopimelic acid, glutamic acid, lysine and aspartic acid. The polar lipid profile contained diphosphatidylglycerol, phosphatidylethanolamine, glycolipids and phospholipids. The dominant cellular fatty acids included anteiso-C15 : 0 and C15 : 0. The genomic DNA G+C content was 50.9 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analysis, strain CFH S0170T is affiliated to the genus Paenibacillus, but could be distinguished from other valid species of this genus. It is concluded that strain CFH S0170T should be considered to represent a novel species of the genus Paenibacillus, for which the name Paenibacillus esterisolvens sp. nov. is proposed. The type strain is CFH S0170T (=KCTC 33624T=BCRC 80802T).}, } @article {pmid29701574, year = {2018}, author = {Lin, P and Yan, ZF and Yi, TH}, title = {Camelliibacillus cellulosilyticus gen. nov., sp. nov., a cellulose-degrading bacterium isolated from tea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1867-1873}, doi = {10.1099/ijsem.0.002755}, pmid = {29701574}, issn = {1466-5034}, mesh = {Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cellulose ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tea/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, oxidase- and catalase-positive, endospore-forming, aerobic, non-motile and rod-shaped bacterium (THG-YT1T) was isolated from green tea. Growth occurred at 10-40 °C (optimum, 25-30 °C), at pH 6-8 (optimum, 7) and at 0-2 % NaCl (optimum, 0 %). Based on 16S rRNA gene sequences, phylogenetic analyses showed that strain THG-YT1T formed a distinct lineage with respect to closely related genera in the family Bacillaceae. Strain THG-YT1T was most closely related to the genera within the families Pullulanibacillus, Scopulibacillus, Tuberibacillus and Caenibacillu, with levels of 16S rRNA gene sequence similarity to the type species of members of these genera of less than 95.0 %. The menaquinone was MK-7. The polar lipids were phosphatidylethanolamine, two unidentified aminophospholipids, two unidentified aminolipids and two unidentified glycolipids. The major fatty acids of strain THG-YT1T were C18 : 3ω7c and anteiso-C17 : 0. The cell-wall peptidoglycan type was A1γ with meso-diaminopimelic acid as the diagnostic diamino acid plus alanine and glutamic acid. The cell-wall sugar was glucose. The DNA G+C content of strain THG-YT1T was determined to be 53.5 mol%. Based on the data presented here, strain THG-YT1T represents a novel species of a new genus of the family Bacillaceae, for which the name Camelliibacillus cellulosilyticus gen. nov., sp. nov. is proposed. The type strain is Camelliibacillus cellulosilyticus THG-YT1T(=KACC 19471T=CGMCC 1.16306T).}, } @article {pmid29700966, year = {2018}, author = {Mansour, I and Heppell, CM and Ryo, M and Rillig, MC}, title = {Application of the microbial community coalescence concept to riverine networks.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1832-1845}, doi = {10.1111/brv.12422}, pmid = {29700966}, issn = {1469-185X}, abstract = {Flows of water, soil, litter, and anthropogenic materials in and around rivers lead to the mixing of their resident microbial communities and subsequently to a resultant community distinct from its precursors. Consideration of these events through a new conceptual lens, namely, community coalescence, could provide a means of integrating physical, environmental, and ecological mechanisms to predict microbial community assembly patterns better in these habitats. Here, we review field studies of microbial communities in riverine habitats where environmental mixing regularly occurs, interpret some of these studies within the community coalescence framework and posit novel hypotheses and insights that may be gained in riverine microbial ecology through the application of this concept. Particularly in the face of a changing climate and rivers under increasing anthropogenic pressures, knowledge about the factors governing microbial community assembly is essential to forecast and/or respond to changes in ecosystem function. Additionally, there is the potential for microbial ecology studies in rivers to become a driver of theory development: riverine systems are ideal for coalescence studies because regular and predictable environmental mixing occurs. Data appropriate for testing community coalescence theory could be collected with minimal alteration to existing study designs.}, } @article {pmid29700475, year = {2018}, author = {Wray, NR and Ripke, S and Mattheisen, M and Trzaskowski, M and Byrne, EM and Abdellaoui, A and Adams, MJ and Agerbo, E and Air, TM and Andlauer, TMF and Bacanu, SA and Bækvad-Hansen, M and Beekman, AFT and Bigdeli, TB and Binder, EB and Blackwood, DRH and Bryois, J and Buttenschøn, HN and Bybjerg-Grauholm, J and Cai, N and Castelao, E and Christensen, JH and Clarke, TK and Coleman, JIR and Colodro-Conde, L and Couvy-Duchesne, B and Craddock, N and Crawford, GE and Crowley, CA and Dashti, HS and Davies, G and Deary, IJ and Degenhardt, F and Derks, EM and Direk, N and Dolan, CV and Dunn, EC and Eley, TC and Eriksson, N and Escott-Price, V and Kiadeh, FHF and Finucane, HK and Forstner, AJ and Frank, J and Gaspar, HA and Gill, M and Giusti-Rodríguez, P and Goes, FS and Gordon, SD and Grove, J and Hall, LS and Hannon, E and Hansen, CS and Hansen, TF and Herms, S and Hickie, IB and Hoffmann, P and Homuth, G and Horn, C and Hottenga, JJ and Hougaard, DM and Hu, M and Hyde, CL and Ising, M and Jansen, R and Jin, F and Jorgenson, E and Knowles, JA and Kohane, IS and Kraft, J and Kretzschmar, WW and Krogh, J and Kutalik, Z and Lane, JM and Li, Y and Li, Y and Lind, PA and Liu, X and Lu, L and MacIntyre, DJ and MacKinnon, DF and Maier, RM and Maier, W and Marchini, J and Mbarek, H and McGrath, P and McGuffin, P and Medland, SE and Mehta, D and Middeldorp, CM and Mihailov, E and Milaneschi, Y and Milani, L and Mill, J and Mondimore, FM and Montgomery, GW and Mostafavi, S and Mullins, N and Nauck, M and Ng, B and Nivard, MG and Nyholt, DR and O'Reilly, PF and Oskarsson, H and Owen, MJ and Painter, JN and Pedersen, CB and Pedersen, MG and Peterson, RE and Pettersson, E and Peyrot, WJ and Pistis, G and Posthuma, D and Purcell, SM and Quiroz, JA and Qvist, P and Rice, JP and Riley, BP and Rivera, M and Saeed Mirza, S and Saxena, R and Schoevers, R and Schulte, EC and Shen, L and Shi, J and Shyn, SI and Sigurdsson, E and Sinnamon, GBC and Smit, JH and Smith, DJ and Stefansson, H and Steinberg, S and Stockmeier, CA and Streit, F and Strohmaier, J and Tansey, KE and Teismann, H and Teumer, A and Thompson, W and Thomson, PA and Thorgeirsson, TE and Tian, C and Traylor, M and Treutlein, J and Trubetskoy, V and Uitterlinden, AG and Umbricht, D and Van der Auwera, S and van Hemert, AM and Viktorin, A and Visscher, PM and Wang, Y and Webb, BT and Weinsheimer, SM and Wellmann, J and Willemsen, G and Witt, SH and Wu, Y and Xi, HS and Yang, J and Zhang, F and , and , and Arolt, V and Baune, BT and Berger, K and Boomsma, DI and Cichon, S and Dannlowski, U and de Geus, ECJ and DePaulo, JR and Domenici, E and Domschke, K and Esko, T and Grabe, HJ and Hamilton, SP and Hayward, C and Heath, AC and Hinds, DA and Kendler, KS and Kloiber, S and Lewis, G and Li, QS and Lucae, S and Madden, PFA and Magnusson, PK and Martin, NG and McIntosh, AM and Metspalu, A and Mors, O and Mortensen, PB and Müller-Myhsok, B and Nordentoft, M and Nöthen, MM and O'Donovan, MC and Paciga, SA and Pedersen, NL and Penninx, BWJH and Perlis, RH and Porteous, DJ and Potash, JB and Preisig, M and Rietschel, M and Schaefer, C and Schulze, TG and Smoller, JW and Stefansson, K and Tiemeier, H and Uher, R and Völzke, H and Weissman, MM and Werge, T and Winslow, AR and Lewis, CM and Levinson, DF and Breen, G and Børglum, AD and Sullivan, PF and , }, title = {Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {668-681}, pmid = {29700475}, issn = {1546-1718}, support = {R01 MH061675/MH/NIMH NIH HHS/United States ; U01 MH085520/MH/NIMH NIH HHS/United States ; R01 CA133996/CA/NCI NIH HHS/United States ; P50 CA097007/CA/NCI NIH HHS/United States ; U01 MH046276/MH/NIMH NIH HHS/United States ; R01 ES011740/ES/NIEHS NIH HHS/United States ; U01 MH079469/MH/NIMH NIH HHS/United States ; K01 HL136884/HL/NHLBI NIH HHS/United States ; R01 MH067257/MH/NIMH NIH HHS/United States ; R01 MH060870/MH/NIMH NIH HHS/United States ; R01 MH081800/MH/NIMH NIH HHS/United States ; R01 MH059571/MH/NIMH NIH HHS/United States ; R01 MH059565/MH/NIMH NIH HHS/United States ; U01 MH079470/MH/NIMH NIH HHS/United States ; R01 MH059587/MH/NIMH NIH HHS/United States ; MC_PC_U127561128//Medical Research Council/United Kingdom ; R01 MH059586/MH/NIMH NIH HHS/United States ; R01 HG009658/HG/NHGRI NIH HHS/United States ; U01 MH109532/MH/NIMH NIH HHS/United States ; R01 MH059566/MH/NIMH NIH HHS/United States ; U01 MH094421/MH/NIMH NIH HHS/United States ; S10 OD018164/OD/NIH HHS/United States ; R01 MH059588/MH/NIMH NIH HHS/United States ; U01 MH046318/MH/NIMH NIH HHS/United States ; P50 CA093459/CA/NCI NIH HHS/United States ; U01 MH109528/MH/NIMH NIH HHS/United States ; R01 MH060879/MH/NIMH NIH HHS/United States ; }, abstract = {Major depressive disorder (MDD) is a common illness accompanied by considerable morbidity, mortality, costs, and heightened risk of suicide. We conducted a genome-wide association meta-analysis based in 135,458 cases and 344,901 controls and identified 44 independent and significant loci. The genetic findings were associated with clinical features of major depression and implicated brain regions exhibiting anatomical differences in cases. Targets of antidepressant medications and genes involved in gene splicing were enriched for smaller association signal. We found important relationships of genetic risk for major depression with educational attainment, body mass, and schizophrenia: lower educational attainment and higher body mass were putatively causal, whereas major depression and schizophrenia reflected a partly shared biological etiology. All humans carry lesser or greater numbers of genetic risk factors for major depression. These findings help refine the basis of major depression and imply that a continuous measure of risk underlies the clinical phenotype.}, } @article {pmid29700474, year = {2018}, author = {Evans, LM and Tahmasbi, R and Vrieze, SI and Abecasis, GR and Das, S and Gazal, S and Bjelland, DW and de Candia, TR and , and Goddard, ME and Neale, BM and Yang, J and Visscher, PM and Keller, MC}, title = {Comparison of methods that use whole genome data to estimate the heritability and genetic architecture of complex traits.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {737-745}, pmid = {29700474}, issn = {1546-1718}, support = {R01 DA037904/DA/NIDA NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; R01 MH100141/MH/NIMH NIH HHS/United States ; }, abstract = {Multiple methods have been developed to estimate narrow-sense heritability, h2, using single nucleotide polymorphisms (SNPs) in unrelated individuals. However, a comprehensive evaluation of these methods has not yet been performed, leading to confusion and discrepancy in the literature. We present the most thorough and realistic comparison of these methods to date. We used thousands of real whole-genome sequences to simulate phenotypes under varying genetic architectures and confounding variables, and we used array, imputed, or whole genome sequence SNPs to obtain 'SNP-heritability' estimates. We show that SNP-heritability can be highly sensitive to assumptions about the frequencies, effect sizes, and levels of linkage disequilibrium of underlying causal variants, but that methods that bin SNPs according to minor allele frequency and linkage disequilibrium are less sensitive to these assumptions across a wide range of genetic architectures and possible confounding factors. These findings provide guidance for best practices and proper interpretation of published estimates.}, } @article {pmid29700473, year = {2018}, author = {Werling, DM and Brand, H and An, JY and Stone, MR and Zhu, L and Glessner, JT and Collins, RL and Dong, S and Layer, RM and Markenscoff-Papadimitriou, E and Farrell, A and Schwartz, GB and Wang, HZ and Currall, BB and Zhao, X and Dea, J and Duhn, C and Erdman, CA and Gilson, MC and Yadav, R and Handsaker, RE and Kashin, S and Klei, L and Mandell, JD and Nowakowski, TJ and Liu, Y and Pochareddy, S and Smith, L and Walker, MF and Waterman, MJ and He, X and Kriegstein, AR and Rubenstein, JL and Sestan, N and McCarroll, SA and Neale, BM and Coon, H and Willsey, AJ and Buxbaum, JD and Daly, MJ and State, MW and Quinlan, AR and Marth, GT and Roeder, K and Devlin, B and Talkowski, ME and Sanders, SJ}, title = {An analytical framework for whole-genome sequence association studies and its implications for autism spectrum disorder.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {727-736}, pmid = {29700473}, issn = {1546-1718}, support = {R01 MH110928/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; U01 MH105575/MH/NIMH NIH HHS/United States ; U01 MH100229/MH/NIMH NIH HHS/United States ; K99 DE026824/DE/NIDCR NIH HHS/United States ; U01 MH111660/MH/NIMH NIH HHS/United States ; U01 MH100239/MH/NIMH NIH HHS/United States ; R35 NS097305/NS/NINDS NIH HHS/United States ; U01 MH111658/MH/NIMH NIH HHS/United States ; U01 MH111661/MH/NIMH NIH HHS/United States ; P01 GM061354/GM/NIGMS NIH HHS/United States ; R01 MH109901/MH/NIMH NIH HHS/United States ; R01 HD081256/HD/NICHD NIH HHS/United States ; U01 MH111662/MH/NIMH NIH HHS/United States ; R01 MH109900/MH/NIMH NIH HHS/United States ; }, abstract = {Genomic association studies of common or rare protein-coding variation have established robust statistical approaches to account for multiple testing. Here we present a comparable framework to evaluate rare and de novo noncoding single-nucleotide variants, insertion/deletions, and all classes of structural variation from whole-genome sequencing (WGS). Integrating genomic annotations at the level of nucleotides, genes, and regulatory regions, we define 51,801 annotation categories. Analyses of 519 autism spectrum disorder families did not identify association with any categories after correction for 4,123 effective tests. Without appropriate correction, biologically plausible associations are observed in both cases and controls. Despite excluding previously identified gene-disrupting mutations, coding regions still exhibited the strongest associations. Thus, in autism, the contribution of de novo noncoding variation is probably modest in comparison to that of de novo coding variants. Robust results from future WGS studies will require large cohorts and comprehensive analytical strategies that consider the substantial multiple-testing burden.}, } @article {pmid29700472, year = {2018}, author = {El-Kebir, M and Satas, G and Raphael, BJ}, title = {Inferring parsimonious migration histories for metastatic cancers.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {718-726}, pmid = {29700472}, issn = {1546-1718}, support = {R01 CA180776/CA/NCI NIH HHS/United States ; R01 HG007069/HG/NHGRI NIH HHS/United States ; U24 CA211000/CA/NCI NIH HHS/United States ; }, abstract = {Metastasis is the migration of cancerous cells from a primary tumor to other anatomical sites. Although metastasis was long thought to result from monoclonal seeding, or single cellular migrations, recent phylogenetic analyses of metastatic cancers have reported complex patterns of cellular migrations between sites, including polyclonal migrations and reseeding. However, accurate determination of migration patterns from somatic mutation data is complicated by intratumor heterogeneity and discordance between clonal lineage and cellular migration. We introduce MACHINA, a multi-objective optimization algorithm that jointly infers clonal lineages and parsimonious migration histories of metastatic cancers from DNA sequencing data. MACHINA analysis of data from multiple cancers shows that migration patterns are often not uniquely determined from sequencing data alone and that complicated migration patterns among primary tumors and metastases may be less prevalent than previously reported. MACHINA's rigorous analysis of migration histories will aid in studies of the drivers of metastasis.}, } @article {pmid29700471, year = {2018}, author = {Zhou, Y and Wang, Y and Krause, K and Yang, T and Dongus, JA and Zhang, Y and Turck, F}, title = {Telobox motifs recruit CLF/SWN-PRC2 for H3K27me3 deposition via TRB factors in Arabidopsis.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {638-644}, doi = {10.1038/s41588-018-0109-9}, pmid = {29700471}, issn = {1546-1718}, abstract = {Polycomb repressive complexes (PRCs) control organismic development in higher eukaryotes through epigenetic gene repression1-4. PRC proteins do not contain DNA-binding domains, thus prompting questions regarding how PRCs find their target loci 5 . Here we present genome-wide evidence of PRC2 recruitment by telomere-repeat-binding factors (TRBs) through telobox-related motifs in Arabidopsis. A triple trb1-2, trb2-1, and trb3-2 (trb1/2/3) mutant with a developmental phenotype and a transcriptome strikingly similar to those of strong PRC2 mutants showed redistribution of trimethyl histone H3 Lys27 (H3K27me3) marks and lower H3K27me3 levels, which were correlated with derepression of TRB1-target genes. TRB1-3 physically interacted with the PRC2 proteins CLF and SWN. A SEP3 reporter gene with a telobox mutation showed ectopic expression, which was correlated with H3K27me3 depletion, whereas tethering TRB1 to the mutated cis element partially restored repression. We propose that telobox-related motifs recruit PRC2 through the interaction between TRBs and CLF/SWN, a mechanism essential for H3K27me3 deposition at a subset of target genes.}, } @article {pmid29700470, year = {2018}, author = {Skoglund, P and Mallick, S and Patterson, N and Reich, D}, title = {No evidence for unknown archaic ancestry in South Asia.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {632-633}, doi = {10.1038/s41588-018-0097-9}, pmid = {29700470}, issn = {1546-1718}, } @article {pmid29700469, year = {2018}, author = {Stadhouders, R}, title = {Expanding the toolbox for 3D genomics.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {634-635}, doi = {10.1038/s41588-018-0112-1}, pmid = {29700469}, issn = {1546-1718}, } @article {pmid29700468, year = {2018}, author = {Wray, NR and Gratten, J}, title = {Sizing up whole-genome sequencing studies of common diseases.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {635-637}, doi = {10.1038/s41588-018-0113-0}, pmid = {29700468}, issn = {1546-1718}, } @article {pmid29700467, year = {2018}, author = {Lin, D and Hong, P and Zhang, S and Xu, W and Jamal, M and Yan, K and Lei, Y and Li, L and Ruan, Y and Fu, ZF and Li, G and Cao, G}, title = {Digestion-ligation-only Hi-C is an efficient and cost-effective method for chromosome conformation capture.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {754-763}, doi = {10.1038/s41588-018-0111-2}, pmid = {29700467}, issn = {1546-1718}, abstract = {Chromosome conformation capture (3C) technologies can be used to investigate 3D genomic structures. However, high background noise, high costs, and a lack of straightforward noise evaluation in current methods impede the advancement of 3D genomic research. Here we developed a simple digestion-ligation-only Hi-C (DLO Hi-C) technology to explore the 3D landscape of the genome. This method requires only two rounds of digestion and ligation, without the need for biotin labeling and pulldown. Non-ligated DNA was efficiently removed in a cost-effective step by purifying specific linker-ligated DNA fragments. Notably, random ligation could be quickly evaluated in an early quality-control step before sequencing. Moreover, an in situ version of DLO Hi-C using a four-cutter restriction enzyme has been developed. We applied DLO Hi-C to delineate the genomic architecture of THP-1 and K562 cells and uncovered chromosomal translocations. This technology may facilitate investigation of genomic organization, gene regulation, and (meta)genome assembly.}, } @article {pmid29700466, year = {2018}, author = {}, title = {Straws in a haystack.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {631}, doi = {10.1038/s41588-018-0125-9}, pmid = {29700466}, issn = {1546-1718}, } @article {pmid29700267, year = {2018}, author = {Phillips, C}, title = {My second coming out.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {458}, doi = {10.1126/science.360.6387.458}, pmid = {29700267}, issn = {1095-9203}, } @article {pmid29700266, year = {2018}, author = {Myhrvold, C and Freije, CA and Gootenberg, JS and Abudayyeh, OO and Metsky, HC and Durbin, AF and Kellner, MJ and Tan, AL and Paul, LM and Parham, LA and Garcia, KF and Barnes, KG and Chak, B and Mondini, A and Nogueira, ML and Isern, S and Michael, SF and Lorenzana, I and Yozwiak, NL and MacInnis, BL and Bosch, I and Gehrke, L and Zhang, F and Sabeti, PC}, title = {Field-deployable viral diagnostics using CRISPR-Cas13.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {444-448}, pmid = {29700266}, issn = {1095-9203}, support = {R01 AI099210/AI/NIAID NIH HHS/United States ; R01 MH110049/MH/NIMH NIH HHS/United States ; DP1 HL141201/HL/NHLBI NIH HHS/United States ; R33 AI100190/AI/NIAID NIH HHS/United States ; R01 HG009761/HG/NHGRI NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; R21 AI100190/AI/NIAID NIH HHS/United States ; F30 CA210382/CA/NCI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/genetics ; Bacterial Proteins/*chemistry ; CRISPR-Associated Proteins/*chemistry ; Dengue/*diagnosis ; Dengue Virus/genetics/*isolation & purification ; Endonucleases/*chemistry ; *Enzyme Assays ; Humans ; Microcephaly/diagnosis/virology ; Polymorphism, Single Nucleotide ; RNA, Viral/*analysis ; Zika Virus/genetics/*isolation & purification ; Zika Virus Infection/*diagnosis ; }, abstract = {Mitigating global infectious disease requires diagnostic tools that are sensitive, specific, and rapidly field deployable. In this study, we demonstrate that the Cas13-based SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) platform can detect Zika virus (ZIKV) and dengue virus (DENV) in patient samples at concentrations as low as 1 copy per microliter. We developed HUDSON (heating unextracted diagnostic samples to obliterate nucleases), a protocol that pairs with SHERLOCK for viral detection directly from bodily fluids, enabling instrument-free DENV detection directly from patient samples in <2 hours. We further demonstrate that SHERLOCK can distinguish the four DENV serotypes, as well as region-specific strains of ZIKV from the 2015-2016 pandemic. Finally, we report the rapid (<1 week) design and testing of instrument-free assays to detect clinically relevant viral single-nucleotide polymorphisms.}, } @article {pmid29700265, year = {2018}, author = {Choi, JH and Sim, SE and Kim, JI and Choi, DI and Oh, J and Ye, S and Lee, J and Kim, T and Ko, HG and Lim, CS and Kaang, BK}, title = {Interregional synaptic maps among engram cells underlie memory formation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {430-435}, doi = {10.1126/science.aas9204}, pmid = {29700265}, issn = {1095-9203}, mesh = {Animals ; CA1 Region, Hippocampal/cytology/*physiology ; CA3 Region, Hippocampal/cytology/*physiology ; Conditioning, Classical ; Fear ; Green Fluorescent Proteins/analysis ; HEK293 Cells ; Humans ; Long-Term Potentiation ; Male ; Memory/*physiology ; Mice, Inbred C57BL ; Neuroimaging/methods ; Neuronal Plasticity ; Neurons/*physiology ; Synapses/*physiology ; }, abstract = {Memory resides in engram cells distributed across the brain. However, the site-specific substrate within these engram cells remains theoretical, even though it is generally accepted that synaptic plasticity encodes memories. We developed the dual-eGRASP (green fluorescent protein reconstitution across synaptic partners) technique to examine synapses between engram cells to identify the specific neuronal site for memory storage. We found an increased number and size of spines on CA1 engram cells receiving input from CA3 engram cells. In contextual fear conditioning, this enhanced connectivity between engram cells encoded memory strength. CA3 engram to CA1 engram projections strongly occluded long-term potentiation. These results indicate that enhanced structural and functional connectivity between engram cells across two directly connected brain regions forms the synaptic correlate for memory formation.}, } @article {pmid29700264, year = {2018}, author = {Young, G and Hundt, N and Cole, D and Fineberg, A and Andrecka, J and Tyler, A and Olerinyova, A and Ansari, A and Marklund, EG and Collier, MP and Chandler, SA and Tkachenko, O and Allen, J and Crispin, M and Billington, N and Takagi, Y and Sellers, JR and Eichmann, C and Selenko, P and Frey, L and Riek, R and Galpin, MR and Struwe, WB and Benesch, JLP and Kukura, P}, title = {Quantitative mass imaging of single biological macromolecules.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {423-427}, pmid = {29700264}, issn = {1095-9203}, support = {UM1 AI100663/AI/NIAID NIH HHS/United States ; Z01 HL001786/HL/NHLBI NIH HHS/United States ; }, mesh = {Actins/chemistry ; Amyloidogenic Proteins/chemistry ; Humans ; Interferometry/methods ; Mass Spectrometry/methods ; Microscopy, Interference/*methods ; *Polymerization ; *Protein Aggregation, Pathological ; Proteins/*chemistry ; Single Molecule Imaging/*methods ; Spatio-Temporal Analysis ; }, abstract = {The cellular processes underpinning life are orchestrated by proteins and their interactions. The associated structural and dynamic heterogeneity, despite being key to function, poses a fundamental challenge to existing analytical and structural methodologies. We used interferometric scattering microscopy to quantify the mass of single biomolecules in solution with 2% sequence mass accuracy, up to 19-kilodalton resolution, and 1-kilodalton precision. We resolved oligomeric distributions at high dynamic range, detected small-molecule binding, and mass-imaged proteins with associated lipids and sugars. These capabilities enabled us to characterize the molecular dynamics of processes as diverse as glycoprotein cross-linking, amyloidogenic protein aggregation, and actin polymerization. Interferometric scattering mass spectrometry allows spatiotemporally resolved measurement of a broad range of biomolecular interactions, one molecule at a time.}, } @article {pmid29700263, year = {2018}, author = {Lange, K and Peise, J and Lücke, B and Kruse, I and Vitagliano, G and Apellaniz, I and Kleinmann, M and Tóth, G and Klempt, C}, title = {Entanglement between two spatially separated atomic modes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {416-418}, doi = {10.1126/science.aao2035}, pmid = {29700263}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Modern quantum technologies in the fields of quantum computing, quantum simulation, and quantum metrology require the creation and control of large ensembles of entangled particles. In ultracold ensembles of neutral atoms, nonclassical states have been generated with mutual entanglement among thousands of particles. The entanglement generation relies on the fundamental particle-exchange symmetry in ensembles of identical particles, which lacks the standard notion of entanglement between clearly definable subsystems. Here, we present the generation of entanglement between two spatially separated clouds by splitting an ensemble of ultracold identical particles prepared in a twin Fock state. Because the clouds can be addressed individually, our experiments open a path to exploit the available entangled states of indistinguishable particles for quantum information applications.}, } @article {pmid29700262, year = {2018}, author = {Kunkel, P and Prüfer, M and Strobel, H and Linnemann, D and Frölian, A and Gasenzer, T and Gärttner, M and Oberthaler, MK}, title = {Spatially distributed multipartite entanglement enables EPR steering of atomic clouds.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {413-416}, doi = {10.1126/science.aao2254}, pmid = {29700262}, issn = {1095-9203}, abstract = {A key resource for distributed quantum-enhanced protocols is entanglement between spatially separated modes. However, the robust generation and detection of entanglement between spatially separated regions of an ultracold atomic system remain a challenge. We used spin mixing in a tightly confined Bose-Einstein condensate to generate an entangled state of indistinguishable particles in a single spatial mode. We show experimentally that this entanglement can be spatially distributed by self-similar expansion of the atomic cloud. We used spatially resolved spin read-out to reveal a particularly strong form of quantum correlations known as Einstein-Podolsky-Rosen (EPR) steering between distinct parts of the expanded cloud. Based on the strength of EPR steering, we constructed a witness, which confirmed genuine 5-partite entanglement.}, } @article {pmid29700261, year = {2018}, author = {Fadel, M and Zibold, T and Décamps, B and Treutlein, P}, title = {Spatial entanglement patterns and Einstein-Podolsky-Rosen steering in Bose-Einstein condensates.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {409-413}, doi = {10.1126/science.aao1850}, pmid = {29700261}, issn = {1095-9203}, abstract = {Many-particle entanglement is a fundamental concept of quantum physics that still presents conceptual challenges. Although nonclassical states of atomic ensembles were used to enhance measurement precision in quantum metrology, the notion of entanglement in these systems was debated because the correlations among the indistinguishable atoms were witnessed by collective measurements only. Here, we use high-resolution imaging to directly measure the spin correlations between spatially separated parts of a spin-squeezed Bose-Einstein condensate. We observe entanglement that is strong enough for Einstein-Podolsky-Rosen steering: We can predict measurement outcomes for noncommuting observables in one spatial region on the basis of corresponding measurements in another region with an inferred uncertainty product below the Heisenberg uncertainty bound. This method could be exploited for entanglement-enhanced imaging of electromagnetic field distributions and quantum information tasks.}, } @article {pmid29700260, year = {2018}, author = {Zhu, JB and Watson, EM and Tang, J and Chen, EY}, title = {A synthetic polymer system with repeatable chemical recyclability.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {398-403}, doi = {10.1126/science.aar5498}, pmid = {29700260}, issn = {1095-9203}, abstract = {The development of chemically recyclable polymers offers a solution to the end-of-use issue of polymeric materials and provides a closed-loop approach toward a circular materials economy. However, polymers that can be easily and selectively depolymerized back to monomers typically require low-temperature polymerization methods and also lack physical properties and mechanical strengths required for practical uses. We introduce a polymer system based on γ-butyrolactone (GBL) with a trans-ring fusion at the α and β positions. Such trans-ring fusion renders the commonly considered as nonpolymerizable GBL ring readily polymerizable at room temperature under solvent-free conditions to yield a high-molecular weight polymer. The polymer has enhanced thermostability and can be repeatedly and quantitatively recycled back to its monomer by thermolysis or chemolysis. Mixing of the two enantiomers of the polymer generates a highly crystalline supramolecular stereocomplex.}, } @article {pmid29700259, year = {2018}, author = {González-Varo, JP and Geldmann, J}, title = {Response-"Bee conservation: Key role of managed bees" and "Bee conservation: Inclusive solutions".}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {390}, doi = {10.1126/science.aat3746}, pmid = {29700259}, issn = {1095-9203}, mesh = {Animals ; Bees ; *Conservation of Natural Resources ; *Pollination ; }, } @article {pmid29700258, year = {2018}, author = {Kleijn, D and Biesmeijer, K and Dupont, YL and Nielsen, A and Potts, SG and Settele, J}, title = {Bee conservation: Inclusive solutions.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {389-390}, doi = {10.1126/science.aat2054}, pmid = {29700258}, issn = {1095-9203}, mesh = {Animals ; Bees ; *Conservation of Natural Resources ; *Pollination ; }, } @article {pmid29700257, year = {2018}, author = {Saunders, ME and Smith, TJ and Rader, R}, title = {Bee conservation: Key role of managed bees.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {389}, doi = {10.1126/science.aat1535}, pmid = {29700257}, issn = {1095-9203}, mesh = {Animals ; Bees ; *Conservation of Natural Resources ; *Pollination ; }, } @article {pmid29700256, year = {2018}, author = {Bardill, J and Bader, AC and Garrison, NA and Bolnick, DA and Raff, JA and Walker, A and Malhi, RS and , }, title = {Advancing the ethics of paleogenomics.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {384-385}, pmid = {29700256}, issn = {1095-9203}, support = {K01 HG008818/HG/NHGRI NIH HHS/United States ; R25 HG007158/HG/NHGRI NIH HHS/United States ; }, mesh = {*Bioethical Issues ; *Body Remains ; Europe ; Genomics/*ethics ; Humans ; Paleontology/*ethics ; Population Groups/genetics ; United States ; }, } @article {pmid29700255, year = {2018}, author = {Walter, P and Anderson, D}, title = {Günter Blobel (1936-2018).}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {383}, doi = {10.1126/science.aat7913}, pmid = {29700255}, issn = {1095-9203}, mesh = {Cell Biology/*history ; Germany ; History, 20th Century ; History, 21st Century ; Nobel Prize ; United States ; }, } @article {pmid29700254, year = {2018}, author = {Chertow, DS}, title = {Next-generation diagnostics with CRISPR.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {381-382}, doi = {10.1126/science.aat4982}, pmid = {29700254}, issn = {1095-9203}, mesh = {*CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Editing ; Humans ; }, } @article {pmid29700253, year = {2018}, author = {Sardon, H and Dove, AP}, title = {Plastics recycling with a difference.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {380-381}, doi = {10.1126/science.aat4997}, pmid = {29700253}, issn = {1095-9203}, mesh = {*Plastics ; *Recycling ; Waste Management ; }, } @article {pmid29700252, year = {2018}, author = {Lee, SF and Klenerman, D}, title = {Weighing one protein with light.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {378-379}, doi = {10.1126/science.aat5851}, pmid = {29700252}, issn = {1095-9203}, mesh = {*Dynamic Light Scattering ; *Proteins ; }, } @article {pmid29700251, year = {2018}, author = {Matsushita, M and Pearce, EJ}, title = {Disrupting metabolism to treat autoimmunity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {377-378}, doi = {10.1126/science.aat4984}, pmid = {29700251}, issn = {1095-9203}, mesh = {*Autoimmunity ; Humans ; }, } @article {pmid29700250, year = {2018}, author = {Cavalcanti, D}, title = {Split, but still attached.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {376-377}, doi = {10.1126/science.aat4590}, pmid = {29700250}, issn = {1095-9203}, } @article {pmid29700249, year = {2018}, author = {Tanaka, EM}, title = {Regenerating tissues.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {374-375}, doi = {10.1126/science.aat4588}, pmid = {29700249}, issn = {1095-9203}, mesh = {*Regeneration ; }, } @article {pmid29700248, year = {2018}, author = {Wade, L}, title = {Cleaning up the killing fields.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {371}, doi = {10.1126/science.360.6387.371}, pmid = {29700248}, issn = {1095-9203}, } @article {pmid29700247, year = {2018}, author = {Wade, L}, title = {Peace dividend.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {368-373}, doi = {10.1126/science.360.6387.368}, pmid = {29700247}, issn = {1095-9203}, } @article {pmid29700246, year = {2018}, author = {Pennisi, E}, title = {Chronicling embryos, cell by cell, gene by gene.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {367}, doi = {10.1126/science.360.6387.367}, pmid = {29700246}, issn = {1095-9203}, mesh = {Animals ; Anura/*embryology ; Cell Tracking/*methods ; *Gene Expression Regulation, Developmental ; Sequence Analysis, DNA ; Single-Cell Analysis/*methods ; Zebrafish/*embryology ; Zygote/*metabolism ; }, } @article {pmid29700245, year = {2018}, author = {Rosen, J}, title = {Robotic weather balloon launchers spread in Alaska.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {366}, doi = {10.1126/science.360.6387.366}, pmid = {29700245}, issn = {1095-9203}, } @article {pmid29700244, year = {2018}, author = {Kaiser, J}, title = {Is genome-guided cancer treatment hyped?.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {365}, doi = {10.1126/science.360.6387.365}, pmid = {29700244}, issn = {1095-9203}, mesh = {Drug Approval ; Drug Delivery Systems ; Gene Targeting ; Genome, Human ; Humans ; Insurance Coverage ; Medicare ; *Molecular Targeted Therapy ; Neoplasms/*drug therapy/*genetics ; Precision Medicine/*trends ; *Sequence Analysis, DNA/economics ; United States ; }, } @article {pmid29700243, year = {2018}, author = {Curry, A}, title = {Siberian sculpture is among the oldest monumental art.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {364}, doi = {10.1126/science.360.6387.364}, pmid = {29700243}, issn = {1095-9203}, } @article {pmid29700242, year = {2018}, author = {Clery, D}, title = {Data trove helps pin down the shape of the Milky Way.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {363}, doi = {10.1126/science.360.6387.363}, pmid = {29700242}, issn = {1095-9203}, } @article {pmid29700241, year = {2018}, author = {Lawler, A}, title = {Searching for a Stone Age Odysseus.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {362-363}, doi = {10.1126/science.360.6387.362}, pmid = {29700241}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; Greece ; History, Ancient ; Human Migration/*history ; Humans ; Mediterranean Islands ; *Neanderthals ; Oceans and Seas ; Technology/*history ; }, } @article {pmid29700240, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {360-361}, doi = {10.1126/science.360.6387.360}, pmid = {29700240}, issn = {1095-9203}, } @article {pmid29700239, year = {2018}, author = {Feuer, MJ}, title = {Evidence for opportunity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {359}, doi = {10.1126/science.aat8999}, pmid = {29700239}, issn = {1095-9203}, } @article {pmid29700238, year = {2018}, author = {Lin, J and Nicastro, D}, title = {Asymmetric distribution and spatial switching of dynein activity generates ciliary motility.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {}, doi = {10.1126/science.aar1968}, pmid = {29700238}, issn = {1095-9203}, support = {R01 GM083122/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chlamydomonas ; Cilia/*physiology/ultrastructure ; Dyneins/chemistry/*metabolism/ultrastructure ; Electron Microscope Tomography ; Flagella/*physiology/ultrastructure ; Male ; Microtubules/chemistry/*physiology/ultrastructure ; Sea Urchins ; *Sperm Motility ; Spermatozoa/*physiology ; }, abstract = {Motile cilia and flagella are essential, highly conserved organelles, and their motility is driven by the coordinated activities of multiple dynein isoforms. The prevailing "switch-point" hypothesis posits that dyneins are asymmetrically activated to drive flagellar bending. To test this model, we applied cryo-electron tomography to visualize activity states of individual dyneins relative to their locations along beating flagella of sea urchin sperm cells. As predicted, bending was generated by the asymmetric distribution of dynein activity on opposite sides of the flagellum. However, contrary to predictions, most dyneins were in their active state, and the smaller population of conformationally inactive dyneins switched flagellar sides relative to the bending direction. Thus, our data suggest a "switch-inhibition" mechanism in which force imbalance is generated by inhibiting, rather than activating, dyneins on alternating sides of the flagellum.}, } @article {pmid29700237, year = {2018}, author = {Ilton, M and Bhamla, MS and Ma, X and Cox, SM and Fitchett, LL and Kim, Y and Koh, JS and Krishnamurthy, D and Kuo, CY and Temel, FZ and Crosby, AJ and Prakash, M and Sutton, GP and Wood, RJ and Azizi, E and Bergbreiter, S and Patek, SN}, title = {The principles of cascading power limits in small, fast biological and engineered systems.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {}, doi = {10.1126/science.aao1082}, pmid = {29700237}, issn = {1095-9203}, mesh = {*Biomechanical Phenomena ; Models, Theoretical ; }, abstract = {Mechanical power limitations emerge from the physical trade-off between force and velocity. Many biological systems incorporate power-enhancing mechanisms enabling extraordinary accelerations at small sizes. We establish how power enhancement emerges through the dynamic coupling of motors, springs, and latches and reveal how each displays its own force-velocity behavior. We mathematically demonstrate a tunable performance space for spring-actuated movement that is applicable to biological and synthetic systems. Incorporating nonideal spring behavior and parameterizing latch dynamics allows the identification of critical transitions in mass and trade-offs in spring scaling, both of which offer explanations for long-observed scaling patterns in biological systems. This analysis defines the cascading challenges of power enhancement, explores their emergent effects in biological and engineered systems, and charts a pathway for higher-level analysis and synthesis of power-amplified systems.}, } @article {pmid29700229, year = {2018}, author = {Wagner, DE and Weinreb, C and Collins, ZM and Briggs, JA and Megason, SG and Klein, AM}, title = {Single-cell mapping of gene expression landscapes and lineage in the zebrafish embryo.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {981-987}, pmid = {29700229}, issn = {1095-9203}, support = {R01 GM107733/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 DC015478/DC/NIDCD NIH HHS/United States ; T32 GM080177/GM/NIGMS NIH HHS/United States ; K99 GM121852/GM/NIGMS NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Clonal Evolution/*genetics ; Gene Expression ; *Gene Expression Regulation, Developmental ; Glycoproteins/genetics ; Intercellular Signaling Peptides and Proteins/genetics ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Zebrafish/*embryology/*genetics ; Zebrafish Proteins/*genetics ; }, abstract = {High-throughput mapping of cellular differentiation hierarchies from single-cell data promises to empower systematic interrogations of vertebrate development and disease. Here we applied single-cell RNA sequencing to >92,000 cells from zebrafish embryos during the first day of development. Using a graph-based approach, we mapped a cell-state landscape that describes axis patterning, germ layer formation, and organogenesis. We tested how clonally related cells traverse this landscape by developing a transposon-based barcoding approach (TracerSeq) for reconstructing single-cell lineage histories. Clonally related cells were often restricted by the state landscape, including a case in which two independent lineages converge on similar fates. Cell fates remained restricted to this landscape in embryos lacking the chordin gene. We provide web-based resources for further analysis of the single-cell data.}, } @article {pmid29700228, year = {2018}, author = {Wyant, GA and Abu-Remaileh, M and Frenkel, EM and Laqtom, NN and Dharamdasani, V and Lewis, CA and Chan, SH and Heinze, I and Ori, A and Sabatini, DM}, title = {NUFIP1 is a ribosome receptor for starvation-induced ribophagy.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {751-758}, pmid = {29700228}, issn = {1095-9203}, support = {R01 CA103866/CA/NCI NIH HHS/United States ; T32 GM007287/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R37 AI047389/AI/NIAID NIH HHS/United States ; R01 CA129105/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acids/*deficiency ; Animals ; Autophagosomes/*metabolism ; *Autophagy ; Cell Nucleus/metabolism ; HEK293 Cells ; Humans ; Lysosomes/metabolism ; Mice ; Microtubule-Associated Proteins/metabolism ; Nuclear Proteins/genetics/*metabolism ; Proteome/metabolism ; Proteomics ; RNA-Binding Proteins/genetics/*metabolism ; Receptors, Cytoplasmic and Nuclear/genetics/*metabolism ; Ribosomes/*metabolism ; TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; }, abstract = {The lysosome degrades and recycles macromolecules, signals to the master growth regulator mTORC1 [mechanistic target of rapamycin (mTOR) complex 1], and is associated with human disease. We performed quantitative proteomic analyses of rapidly isolated lysosomes and found that nutrient levels and mTOR dynamically modulate the lysosomal proteome. Upon mTORC1 inhibition, NUFIP1 (nuclear fragile X mental retardation-interacting protein 1) redistributes from the nucleus to autophagosomes and lysosomes. Upon these conditions, NUFIP1 interacts with ribosomes and delivers them to autophagosomes by directly binding to microtubule-associated proteins 1A/1B light chain 3B (LC3B). The starvation-induced degradation of ribosomes via autophagy (ribophagy) depends on the capacity of NUFIP1 to bind LC3B and promotes cell survival. We propose that NUFIP1 is a receptor for the selective autophagy of ribosomes.}, } @article {pmid29700227, year = {2018}, author = {Briggs, JA and Weinreb, C and Wagner, DE and Megason, S and Peshkin, L and Kirschner, MW and Klein, AM}, title = {The dynamics of gene expression in vertebrate embryogenesis at single-cell resolution.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {}, pmid = {29700227}, issn = {1095-9203}, support = {T32 GM080177/GM/NIGMS NIH HHS/United States ; R01 HD073104/HD/NICHD NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R33 CA212697/CA/NCI NIH HHS/United States ; R21 HD087723/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*genetics ; Embryonic Development/*genetics ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Genetic Variation ; Neural Crest/cytology/embryology ; Neurogenesis/genetics ; Pluripotent Stem Cells/metabolism ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Transcription Factors ; Transcriptome ; Xenopus/*embryology/*genetics ; Zebrafish/embryology/genetics ; Zygote ; }, abstract = {Time series of single-cell transcriptome measurements can reveal dynamic features of cell differentiation pathways. From measurements of whole frog embryos spanning zygotic genome activation through early organogenesis, we derived a detailed catalog of cell states in vertebrate development and a map of differentiation across all lineages over time. The inferred map recapitulates most if not all developmental relationships and associates new regulators and marker genes with each cell state. We find that many embryonic cell states appear earlier than previously appreciated. We also assess conflicting models of neural crest development. Incorporating a matched time series of zebrafish development from a companion paper, we reveal conserved and divergent features of vertebrate early developmental gene expression programs.}, } @article {pmid29700226, year = {2018}, author = {Grigoli, F and Cesca, S and Rinaldi, AP and Manconi, A and López-Comino, JA and Clinton, JF and Westaway, R and Cauzzi, C and Dahm, T and Wiemer, S}, title = {The November 2017 Mw 5.5 Pohang earthquake: A possible case of induced seismicity in South Korea.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1003-1006}, doi = {10.1126/science.aat2010}, pmid = {29700226}, issn = {1095-9203}, abstract = {The moment magnitude (Mw) 5.5 earthquake that struck South Korea in November 2017 was one of the largest and most damaging events in that country over the past century. Its proximity to an enhanced geothermal system site, where high-pressure hydraulic injection had been performed during the previous 2 years, raises the possibility that this earthquake was anthropogenic. We have combined seismological and geodetic analyses to characterize the mainshock and its largest aftershocks, constrain the geometry of this seismic sequence, and shed light on its causal factors. According to our analysis, it seems plausible that the occurrence of this earthquake was influenced by the aforementioned industrial activities. Finally, we found that the earthquake transferred static stress to larger nearby faults, potentially increasing the seismic hazard in the area.}, } @article {pmid29700225, year = {2018}, author = {Farrell, JA and Wang, Y and Riesenfeld, SJ and Shekhar, K and Regev, A and Schier, AF}, title = {Single-cell reconstruction of developmental trajectories during zebrafish embryogenesis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {}, pmid = {29700225}, issn = {1095-9203}, support = {K99 HD091291/HD/NICHD NIH HHS/United States ; DP1 HD094764/HD/NICHD NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U01 MH105960/MH/NIMH NIH HHS/United States ; R01 HD085905/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Blastula/embryology/metabolism ; Embryo, Nonmammalian/embryology/metabolism ; Embryonic Development/*genetics ; *Gene Expression Regulation, Developmental ; High-Throughput Nucleotide Sequencing ; Signal Transduction ; Single-Cell Analysis ; Transcription, Genetic ; Transcriptome ; Zebrafish/*embryology/*genetics ; Zebrafish Proteins/*genetics ; }, abstract = {During embryogenesis, cells acquire distinct fates by transitioning through transcriptional states. To uncover these transcriptional trajectories during zebrafish embryogenesis, we sequenced 38,731 cells and developed URD, a simulated diffusion-based computational reconstruction method. URD identified the trajectories of 25 cell types through early somitogenesis, gene expression along them, and their spatial origin in the blastula. Analysis of Nodal signaling mutants revealed that their transcriptomes were canalized into a subset of wild-type transcriptional trajectories. Some wild-type developmental branch points contained cells that express genes characteristic of multiple fates. These cells appeared to trans-specify from one fate to another. These findings reconstruct the transcriptional trajectories of a vertebrate embryo, highlight the concurrent canalization and plasticity of embryonic specification, and provide a framework with which to reconstruct complex developmental trees from single-cell transcriptomes.}, } @article {pmid29700224, year = {2018}, author = {Kim, KH and Ree, JH and Kim, Y and Kim, S and Kang, SY and Seo, W}, title = {Assessing whether the 2017 Mw 5.4 Pohang earthquake in South Korea was an induced event.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6392}, pages = {1007-1009}, doi = {10.1126/science.aat6081}, pmid = {29700224}, issn = {1095-9203}, abstract = {The moment magnitude (Mw) 5.4 Pohang earthquake, the most damaging event in South Korea since instrumental seismic observation began in 1905, occurred beneath the Pohang geothermal power plant in 2017. Geological and geophysical data suggest that the Pohang earthquake was induced by fluid from an enhanced geothermal system (EGS) site, which was injected directly into a near-critically stressed subsurface fault zone. The magnitude of the mainshock makes it the largest known induced earthquake at an EGS site.}, } @article {pmid29699591, year = {2018}, author = {Kramer, F and Just, S and Zeller, T}, title = {New perspectives: systems medicine in cardiovascular disease.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {57}, pmid = {29699591}, issn = {1752-0509}, support = {01ZX1407A//BMBF/ ; FKZ01ZX1508//BMBF/ ; FKZ031L0024A//BMBF/ ; FKZ01ZX1408A//BMBF/ ; }, abstract = {BACKGROUND: Cardiovascular diseases (CVD) represent one of the most important causes of morbidity and mortality worldwide. Innovative approaches to increase the understanding of the underpinnings of CVD promise to enhance CVD risk assessment and might pave the way to tailored therapies. Within the last years, systems medicine has emerged as a novel tool to study the genetic, molecular and physiological interactions.

CONCLUSION: In this review, we provide an overview of the current molecular-experimental, epidemiological and bioinformatical tools applied in systems medicine in the cardiovascular field. We will discuss the status and challenges in implementing interdisciplinary systems medicine approaches in CVD.}, } @article {pmid29699504, year = {2018}, author = {Zilio, G and Thiévent, K and Koella, JC}, title = {Host genotype and environment affect the trade-off between horizontal and vertical transmission of the parasite Edhazardia aedis.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {59}, pmid = {29699504}, issn = {1471-2148}, mesh = {Aedes/parasitology ; Animals ; *Environment ; Genotype ; Host-Parasite Interactions/*genetics ; Life Cycle Stages ; Microsporidia/growth & development/*physiology ; Microsporidiosis/*parasitology/*transmission ; Parasites/*genetics/growth & development ; Reproduction ; Virulence ; }, abstract = {BACKGROUND: If a parasite is able to transmit horizontally or vertically, which transmission mode will it choose? We investigated how the growth conditions and the genotype of the mosquito Aedes aegypti affect the transmission mode of the parasite Edhazardia aedis.

RESULTS: In poor conditions the parasites were more likely to be transmitted horizontally, whereas in favourable conditions they were more likely to be transmitted vertically. Unfavourable conditions delayed emergence, giving the parasite more time to produce its horizontally transmitted stage; in more favourable conditions mosquitoes have greater reproductive success, increasing the effectiveness of vertical transmission. In addition, the parasite's ability to transmit vertically was influenced by the genetic background of the host (i.e., its full-sib family), giving a genetic correlation between the host's life-history and which of the parasite's transmission mode it enables. In particular, genotypes with large bodies (and therefore high fecundity) were more likely to enable vertical transmission than genotypes with small bodies. This led to a trade-off among the host's families (which can be interpreted as a genetic correlation) for the parasite's transmission mode.

CONCLUSIONS: Since horizontal transmission is linked to higher virulence than vertical transmission, the host's contribution to transmission mode has important consequences for the evolution of parasites with mixed-mode transmission.}, } @article {pmid29699502, year = {2018}, author = {Schilling, MP and Gompert, Z and Li, FW and Windham, MD and Wolf, PG}, title = {Admixture, evolution, and variation in reproductive isolation in the Boechera puberula clade.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {61}, pmid = {29699502}, issn = {1471-2148}, support = {DEB-0816560//National Science Foundation/International ; }, mesh = {Alleles ; Animals ; Biological Evolution ; Brassicaceae/*genetics ; Diploidy ; *Genetic Variation ; Genotype ; Hybridization, Genetic ; Microsatellite Repeats/genetics ; North America ; *Phylogeny ; Ploidies ; Principal Component Analysis ; *Reproductive Isolation ; }, abstract = {BACKGROUND: Hybridization is very common in plants, and the incorporation of new alleles into existing lineages (i.e. admixture) can blur species boundaries. However, admixture also has the potential to increase standing genetic variation. With new sequencing methods, we can now study admixture and reproductive isolation at a much finer scale than in the past. The genus Boechera is an extraordinary example of admixture, with over 400 hybrid derivates of varying ploidy levels. Yet, few studies have assessed admixture in this genus on a genomic scale.

RESULTS: In this study, we used Genotyping-by-Sequencing (GBS) to clarify the evolution of the Boechera puberula clade, whose six members are scattered across the western United States. We further assessed patterns of admixture and reproductive isolation within the group, including two additional species (B. stricta and B. retrofracta) that are widespread across North America. Based on 14,815 common genetic variants, we found evidence for some cases of hybridization. We find evidence of both recent and more ancient admixture, and that levels of admixture vary across species.

CONCLUSIONS: We present evidence for a monophyletic origin of the B. puberula group, and a split of B. puberula into two subspecies. Further, when inferring reproductive isolation on the basis of presence and absence of admixture, we found that the accumulation of reproductive isolation between species does not seem to occur linearly with time since divergence in this system. We discuss our results in the context of sexuality and asexuality in Boechera.}, } @article {pmid29699497, year = {2018}, author = {Budczies, J and Pfarr, N and Romanovsky, E and Endris, V and Stenzinger, A and Denkert, C}, title = {Ioncopy: an R Shiny app to call copy number alterations in targeted NGS data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {157}, pmid = {29699497}, issn = {1471-2105}, support = {TransLUMINAL-B//Deutsche Krebshilfe/International ; }, mesh = {*DNA Copy Number Variations ; *Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Neoplasms/*genetics ; *Software ; }, abstract = {BACKGROUND: Somatic copy number alterations (CNAs) contribute to the clinically targetable aberrations in the tumor genome. For both routine diagnostics and biomarkers research, CNA analysis in a single assay together with somatic mutations is highly desirable.

RESULTS: Ioncopy is a validated method and easy-to-use software for CNA calling from targeted NGS data. Copy number and significance of CNA are estimated for each gene in each sample. Copy number gains and losses are called after multiple testing corrections controlling FWER or FDR.

CONCLUSIONS: Ioncopy facilitates calling of CNAs in a cohort of tumors tissues with or without using normal (germline) DNA controls.}, } @article {pmid29699496, year = {2018}, author = {Li, Z and Rouse, R}, title = {Co-sequencing and novel delayed anti-correlation identify function for pancreatic enriched microRNA biomarkers in a rat model of acute pancreatic injury.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {297}, pmid = {29699496}, issn = {1471-2164}, mesh = {Animals ; Biomarkers/*metabolism ; *Gene Expression Profiling ; High-Throughput Nucleotide Sequencing/*methods ; Male ; MicroRNAs/*genetics ; Pancreas/*metabolism/pathology ; Pancreatic Diseases/*genetics/pathology ; RNA, Messenger/genetics ; Rats ; Rats, Sprague-Dawley ; }, abstract = {BACKGROUND: Co-sequencing of messenger ribonucleic acid (mRNA) and micro ribonucleic acid (miRNA) across a time series (1, 3, 6, 24, and 48 h post injury) was used to identify potential miRNA-gene interactions during pancreatic injury, associate serum and tissue levels of candidate miRNA biomarkers of pancreatic injury, and functionally link these candidate miRNA biomarkers to observed histopathology. RNAs were derived from pancreatic tissues obtained in experiments characterizing the serum levels of candidate miRNA biomarkers in response to acute pancreatic injury in rats.

RESULTS: No correlation was discovered between tissue and serum levels of the miRNAs. A combination of differential gene expression, novel delayed anti-correlation analysis and experimental database interrogation was used to identify messenger RNAs and miRNAs that experienced significant expression change across the time series, that were negatively correlated, that were complementary in sequence, and that had experimentally supported relationships. This approach yielded a complex signaling network for future investigation and a link for the specific candidate miRNA biomarkers, miR-216a-5p and miR-217-5p, to cellular processes that were in fact the prominent histopathology observations in the same experimental samples. RNA quality bias by treatment was observed in the study samples and a statistical correction was applied. The relevance and impact of that correction on significant results is discussed.

CONCLUSION: The described approach allowed extraction of miRNA function from genomic data and defined a mechanistic anchor for these miRNAs as biomarkers. Functional and mechanistic conclusions are supported by histopathology findings.}, } @article {pmid29699489, year = {2018}, author = {Martínez-Barnetche, J and Lavore, A and Beliera, M and Téllez-Sosa, J and Zumaya-Estrada, FA and Palacio, V and Godoy-Lozano, E and Rivera-Pomar, R and Rodríguez, MH}, title = {Adaptations in energy metabolism and gene family expansions revealed by comparative transcriptomics of three Chagas disease triatomine vectors.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {296}, pmid = {29699489}, issn = {1471-2164}, support = {None//Agencia Mexicana de Cooperación Internacional para el Desarrollo/ ; PICT-2013-1554//Agencia Nacional de Promoción de Ciencia y Técnica/ ; 19612//Concejo Nacional de Ciencia y Tecnología/ ; FO-AR 5790//Ministerio de Relaciones Exteriores de Argentina/ ; }, mesh = {Adaptation, Physiological ; Animals ; Biological Evolution ; Chagas Disease/epidemiology/*parasitology/transmission ; Ecology ; *Energy Metabolism ; Genome, Insect ; *Genomics ; Insect Vectors/classification/*genetics/metabolism/parasitology ; Multigene Family ; South America ; *Transcriptome ; Triatoma/classification/*genetics/metabolism/parasitology ; }, abstract = {BACKGROUND: Chagas disease is a parasitic infection caused by Trypanosoma cruzi. It is an important public health problem affecting around seven to eight million people in the Americas. A large number of hematophagous triatomine insect species, occupying diverse natural and human-modified ecological niches transmit this disease. Triatomines are long-living hemipterans that have evolved to explode different habitats to associate with their vertebrate hosts. Understanding the molecular basis of the extreme physiological conditions including starvation tolerance and longevity could provide insights for developing novel control strategies. We describe the normalized cDNA, full body transcriptome analysis of three main vectors in North, Central and South America, Triatoma pallidipennis, T. dimidiata and T. infestans.

RESULTS: Two-thirds of the de novo assembled transcriptomes map to the Rhodnius prolixus genome and proteome. A Triatoma expansion of the calycin family and two types of protease inhibitors, pacifastins and cystatins were identified. A high number of transcriptionally active class I transposable elements was documented in T. infestans, compared with T. dimidiata and T. pallidipennis. Sequence identity in Triatoma-R. prolixus 1:1 orthologs revealed high sequence divergence in four enzymes participating in gluconeogenesis, glycogen synthesis and the pentose phosphate pathway, indicating high evolutionary rates of these genes. Also, molecular evidence suggesting positive selection was found for several genes of the oxidative phosphorylation I, III and V complexes.

CONCLUSIONS: Protease inhibitors and calycin-coding gene expansions provide insights into rapidly evolving processes of protease regulation and haematophagy. Higher evolutionary rates in enzymes that exert metabolic flux control towards anabolism and evidence for positive selection in oxidative phosphorylation complexes might represent genetic adaptations, possibly related to prolonged starvation, oxidative stress tolerance, longevity, and hematophagy and flight reduction. Overall, this work generated novel hypothesis related to biological adaptations to extreme physiological conditions and diverse ecological niches that sustain Chagas disease transmission.}, } @article {pmid29699488, year = {2018}, author = {Simões, P and Pascual, M}, title = {Patterns of geographic variation of thermal adapted candidate genes in Drosophila subobscura sex chromosome arrangements.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {60}, pmid = {29699488}, issn = {1471-2148}, support = {SFRH/BPD/36829/2007//Fundação para a Ciência e a Tecnologia/International ; SFRH/BPD/86186/2012//Fundação para a Ciência e a Tecnologia/International ; project CTM2013-48163//Spanish Government/International ; CTM2017-88080 (AEI/FEDER, UE)//Spanish Government/International ; research groups SGR2014-336//Generalitat de Catalunya/International ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; Base Sequence ; Drosophila/*genetics ; Gene Flow ; Gene Rearrangement ; *Genes, Insect ; *Genetic Association Studies ; Genetic Variation ; *Geography ; Linkage Disequilibrium/genetics ; Nucleotides/genetics ; Polymorphism, Genetic ; Principal Component Analysis ; Sex Chromosomes/*genetics ; *Temperature ; }, abstract = {BACKGROUND: The role of chromosomal arrangements in adaptation is supported by the repeatable clinal variation in inversion frequencies across continents in colonizing species such as Drosophila subobscura. However, there is a lack of knowledge on the genetic variation in genes within inversions, possibly targets of climatic selection, across a geographic latitudinal gradient. In the present study we analysed four candidate loci for thermal adaptation, located close to the breakpoints, in two chromosomal arrangements of the sex (A) chromosome of Drosophila subobscura with different thermal preferences. Individual chromosomes with A2 (the inverted arrangement considered warm adapted) or AST (the standard ancestral arrangement considered cold adapted) were sequenced across four European localities at varying latitudes, up to ~ 2500 Kms apart.

RESULTS: Importantly, we found very low differentiation for each specific arrangement across populations as well as no clinal patterns of genomic variation. This suggests wide gene exchange along the cline. Differentiation between the sex chromosome arrangements was significant in the two more proximal regions relative to the AST orientation but not in the distal ones, independently of their location inside or outside the inversion. This can be possibly due to variation in the levels of gene flux and/or selection acting in these regions.

CONCLUSIONS: Gene flow appears to have homogenized the genetic content within-arrangement at a wide geographical scale, despite the expected diverse selective pressures in the specific natural environments of the different populations sampled. It is thus likely that the inversion frequency clines in this species are being maintained by local adaptation in face of gene flow. The differences between arrangements at non-coding regions might be associated with the previously observed differential gene expression in different thermal regimes. Higher resolution genomic scans for individual chromosomal arrangements performed over a large environmental gradient are needed to find the targets of selection and further elucidate the adaptive mechanisms maintaining chromosomal inversion polymorphisms.}, } @article {pmid29699487, year = {2018}, author = {Takisawa, R and Nakazaki, T and Nunome, T and Fukuoka, H and Kataoka, K and Saito, H and Habu, T and Kitajima, A}, title = {The parthenocarpic gene Pat-k is generated by a natural mutation of SlAGL6 affecting fruit development in tomato (Solanum lycopersicum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {72}, pmid = {29699487}, issn = {1471-2229}, support = {15K18639//Japan Society for the Promotion of Science/ ; }, mesh = {Chromosome Mapping ; Flowers/growth & development/ultrastructure ; Fruit/*genetics/growth & development ; Genes, Plant/*genetics/physiology ; Genome, Plant/genetics ; Lod Score ; Lycopersicon esculentum/*genetics/growth & development ; Mutation/genetics ; Parthenogenesis/*genetics ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Seeds/growth & development ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Parthenocarpy is a desired trait in tomato because it can overcome problems with fruit setting under unfavorable environmental conditions. A parthenocarpic tomato cultivar, 'MPK-1', with a parthenocarpic gene, Pat-k, exhibits stable parthenocarpy that produces few seeds. Because 'MPK-1' produces few seeds, seedlings are propagated inefficiently via cuttings. It was reported that Pat-k is located on chromosome 1. However, the gene had not been isolated and the relationship between the parthenocarpy and low seed set in 'MPK-1' remained unclear. In this study, we isolated Pat-k to clarify the relationship between parthenocarpy and low seed set in 'MPK-1'.

RESULTS: Using quantitative trait locus (QTL) analysis for parthenocarpy and seed production, we detected a major QTL for each trait on nearly the same region of the Pat-k locus on chromosome 1. To isolate Pat-k, we performed fine mapping using an F4 population following the cross between a non-parthenocarpic cultivar, 'Micro-Tom' and 'MPK-1'. The results showed that Pat-k was located in the 529 kb interval between two markers, where 60 genes exist. By using data from a whole genome re-sequencing and genome sequence analysis of 'MPK-1', we could identify that the SlAGAMOUS-LIKE 6 (SlAGL6) gene of 'MPK-1' was mutated by a retrotransposon insertion. The transcript level of SlAGL6 was significantly lower in ovaries of 'MPK-1' than a non-parthenocarpic cultivar. From these results, we could conclude that Pat-k is SlAGL6, and its down-regulation in 'MPK-1' causes parthenocarpy and low seed set. In addition, we observed abnormal micropyles only in plants homozygous for the 'MPK-1' allele at the Pat-k/SlAGL6 locus. This result suggests that Pat-k/SlAGL6 is also related to ovule formation and that the low seed set in 'MPK-1' is likely caused by abnormal ovule formation through down-regulation of Pat-k/SlAGL6.

CONCLUSIONS: Pat-k is identical to SlAGL6, and its down-regulation causes parthenocarpy and low seed set in 'MPK-1'. Moreover, down-regulation of Pat-k/SlAGL6 could cause abnormal ovule formation, leading to a reduction in the number of seeds.}, } @article {pmid29699486, year = {2018}, author = {Krempel, R and Kulkarni, P and Yim, A and Lang, U and Habermann, B and Frommolt, P}, title = {Integrative analysis and machine learning on cancer genomics data using the Cancer Systems Biology Database (CancerSysDB).}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {156}, pmid = {29699486}, issn = {1471-2105}, support = {PF3313/2-1//Deutsche Forschungsgemeinschaft/International ; HA 6905/2-1//Deutsche Forschungsgemeinschaft/International ; LA 919/6-1//Deutsche Forschungsgemeinschaft/International ; KF2429610MS2//Bundesministerium für Wirtschaft und Technologie/International ; }, mesh = {*Databases, Factual ; Exome ; Genomics/*methods ; Humans ; *Machine Learning ; Neoplasms/*genetics ; *Software ; *Systems Biology ; }, abstract = {BACKGROUND: Recent cancer genome studies on many human cancer types have relied on multiple molecular high-throughput technologies. Given the vast amount of data that has been generated, there are surprisingly few databases which facilitate access to these data and make them available for flexible analysis queries in the broad research community. If used in their entirety and provided at a high structural level, these data can be directed into constantly increasing databases which bear an enormous potential to serve as a basis for machine learning technologies with the goal to support research and healthcare with predictions of clinically relevant traits.

RESULTS: We have developed the Cancer Systems Biology Database (CancerSysDB), a resource for highly flexible queries and analysis of cancer-related data across multiple data types and multiple studies. The CancerSysDB can be adopted by any center for the organization of their locally acquired data and its integration with publicly available data from multiple studies. A publicly available main instance of the CancerSysDB can be used to obtain highly flexible queries across multiple data types as shown by highly relevant use cases. In addition, we demonstrate how the CancerSysDB can be used for predictive cancer classification based on whole-exome data from 9091 patients in The Cancer Genome Atlas (TCGA) research network.

CONCLUSIONS: Our database bears the potential to be used for large-scale integrative queries and predictive analytics of clinically relevant traits.}, } @article {pmid29699485, year = {2018}, author = {Gomes, AJB and Nagamachi, CY and Rodrigues, LRR and Ferguson-Smith, MA and Yang, F and O'Brien, PCM and Pieczarka, JC}, title = {Chromosomal evolution and phylogeny in the Nullicauda group (Chiroptera, Phyllostomidae): evidence from multidirectional chromosome painting.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {62}, pmid = {29699485}, issn = {1471-2148}, support = {552032/2010-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)/International ; 064/2008//Fundação Amazônia Paraense de Amparo à Pesquisa/International ; 064/2011//Fundação Amazônia Paraense de Amparo à Pesquisa/International ; 047/2012//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/International ; 2.318.697.0001//Banco Nacional de Desenvolvimento Economico e Social/International ; 308428/2013-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; 308401/2013-1//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; }, mesh = {Animals ; Chiroptera/*classification/*genetics ; Chromosome Banding ; *Chromosome Painting ; Chromosomes, Mammalian/*genetics ; *Evolution, Molecular ; Humans ; Karyotype ; Karyotyping ; *Phylogeny ; Software ; }, abstract = {BACKGROUND: The family Phyllostomidae (Chiroptera) shows wide morphological, molecular and cytogenetic variation; many disagreements regarding its phylogeny and taxonomy remains to be resolved. In this study, we use chromosome painting with whole chromosome probes from the Phyllostomidae Phyllostomus hastatus and Carollia brevicauda to determine the rearrangements among several genera of the Nullicauda group (subfamilies Gliphonycterinae, Carolliinae, Rhinophyllinae and Stenodermatinae).

RESULTS: These data, when compared with previously published chromosome homology maps, allow the construction of a phylogeny comparable to those previously obtained by morphological and molecular analysis. Our phylogeny is largely in agreement with that proposed with molecular data, both on relationships between the subfamilies and among genera; it confirms, for instance, that Carollia and Rhinophylla, previously considered as part of the same subfamily are, in fact, distant genera.

CONCLUSIONS: The occurrence of the karyotype considered ancestral for this family in several different branches suggests that the diversification of Phyllostomidae into many subfamilies has occurred in a short period of time. Finally, the comparison with published maps using human whole chromosome probes allows us to track some syntenic associations prior to the emergence of this family.}, } @article {pmid29699484, year = {2018}, author = {Doshi, J and Kuppili, RR and Gurdasani, S and Venkatakrishnan, N and Saxena, A and Bose, K}, title = {PDZscape: a comprehensive PDZ-protein database.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {160}, pmid = {29699484}, issn = {1471-2105}, mesh = {*Databases, Protein ; Humans ; *PDZ Domains ; Software ; Statistics as Topic ; User-Computer Interface ; }, abstract = {PDZ-containing proteins comprise one of the most widely distributed protein families playing major role in localization and membrane receptor clustering. They are hence important regulators of signal transduction in cellular pathways. Although knowledge on these proteins has increased exponentially, the existing database 'PDZBase' is limited by presence of only 339 proteins as it dates back to 2004 when very little data was available. Thus, lack of exclusive information on this protein family led us to develop PDZscape. 'PDZscape' encompasses the complete available information on 58,648 PDZ-containing proteins with their known and putative binding partners on one platform. It has a user-friendly web interface that can be easily queried with external protein identifiers. With unique integration of prominent databases including NCBI, UniProtKB, Swiss-Prot, Pubmed, PDB, STRING, IntAct, KEGG, Pfam and Protein Mutant Database, it provides detailed information on PDZ interactome apart from the customized BLAST option. Most importantly, this database encompasses the mutations and diseases associated with PDZ containing proteins manually curated by our group, thus making it a comprehensive compilation. It also features tools to query the database using sequence (PDZ-Blast) and to find if protein of interest is a PDZ-binding protein. PDZscape is freely available at http://www.actrec.gov.in:8080/pdzscape .}, } @article {pmid29699483, year = {2018}, author = {Tan, KK and Zulkifle, NI and Sulaiman, S and Pang, SP and NorAmdan, N and MatRahim, N and Abd-Jamil, J and Shu, MH and Mahadi, NM and AbuBakar, S}, title = {Emergence of the Asian lineage dengue virus type 3 genotype III in Malaysia.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {58}, pmid = {29699483}, issn = {1471-2148}, support = {07-05-MGI-GMB015//Kementerian Sains, Teknologi dan Inovasi/International ; LRGS/TD/2011/UM/Penyakit Berjangkit//Ministry of Higher Education, Malaysia/International ; PS152/2008C//Universiti Malaya/International ; }, mesh = {Amino Acid Substitution/genetics ; Dengue/epidemiology ; Dengue Virus/classification/*genetics/isolation & purification ; Genetic Variation ; Genotype ; Geography ; Humans ; Internationality ; Malaysia ; Open Reading Frames/genetics ; *Phylogeny ; Phylogeography ; Selection, Genetic ; }, abstract = {BACKGROUND: Dengue virus type 3 genotype III (DENV3/III) is associated with increased number of severe infections when it emerged in the Americas and Asia. We had previously demonstrated that the DENV3/III was introduced into Malaysia in the late 2000s. We investigated the genetic diversity of DENV3/III strains recovered from Malaysia and examined their phylogenetic relationships against other DENV3/III strains isolated globally.

RESULTS: Phylogenetic analysis revealed at least four distinct DENV3/III lineages. Two of the lineages (DENV3/III-B and DENV3/III-C) are current actively circulating whereas the DENV3/III-A and DENV3/III-D were no longer recovered since the 1980s. Selection pressure analysis revealed strong evidence of positive selection on a number of amino acid sites in PrM, E, NS1, NS2a, NS2b, NS3, NS4a, and NS5. The Malaysian DENV3/III isolates recovered in the 1980s (MY.59538/1987) clustered into DENV3/III-B, which was the lineage with cosmopolitan distribution consisting of strains actively circulating in the Americas, Africa, and Asia. The Malaysian isolates recovered after the 2000s clustered within DENV3/III-C. This DENV3/III-C lineage displayed a more restricted geographical distribution and consisted of isolates recovered from Asia, denoted as the Asian lineage. Amino acid variation sites in NS5 (NS5-553I/M, NS5-629 T, and NS5-820E) differentiated the DENV3/III-C from other DENV3 viruses. The codon 629 of NS5 was identified as a positively selected site. While the NS5-698R was identified as unique to the genome of DENV3/III-C3. Phylogeographic results suggested that the recent Malaysian DENV3/III-C was likely to have been introduced from Singapore in 2008 and became endemic. From Malaysia, the virus subsequently spread into Taiwan and Thailand in the early part of the 2010s and later reintroduced into Singapore in 2013.

CONCLUSIONS: Distinct clustering of the Malaysian old and new DENV3/III isolates suggests that the currently circulating DENV3/III in Malaysia did not descend directly from the strains recovered during the 1980s. Phylogenetic analyses and common genetic traits in the genome of the strains and those from the neighboring countries suggest that the Malaysian DENV3/III is likely to have been introduced from the neighboring regions. Malaysia, however, serves as one of the sources of the recent regional spread of DENV3/III-C3 within the Asia region.}, } @article {pmid29699482, year = {2018}, author = {Mitić, NS and Malkov, SN and Kovačević, JJ and Pavlović-Lažetić, GM and Beljanski, MV}, title = {Structural disorder of plasmid-encoded proteins in Bacteria and Archaea.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {158}, pmid = {29699482}, issn = {1471-2105}, support = {174021//Ministry of Education, Science and Technological Development, Republic of Serbia/International ; }, mesh = {Archaea/*genetics ; Archaeal Proteins/*chemistry ; Bacteria/*genetics ; Bacterial Proteins/*chemistry ; Chromosomes, Archaeal/metabolism ; Chromosomes, Bacterial/metabolism ; Intrinsically Disordered Proteins/*chemistry ; Plasmids/*metabolism ; Proteome/metabolism ; Toxins, Biological/chemistry ; }, abstract = {BACKGROUND: In the last decade and a half it has been firmly established that a large number of proteins do not adopt a well-defined (ordered) structure under physiological conditions. Such intrinsically disordered proteins (IDPs) and intrinsically disordered (protein) regions (IDRs) are involved in essential cell processes through two basic mechanisms: the entropic chain mechanism which is responsible for rapid fluctuations among many alternative conformations, and molecular recognition via short recognition elements that bind to other molecules. IDPs possess a high adaptive potential and there is special interest in investigating their involvement in organism evolution.

RESULTS: We analyzed 2554 Bacterial and 139 Archaeal proteomes, with a total of 8,455,194 proteins for disorder content and its implications for adaptation of organisms, using three disorder predictors and three measures. Along with other findings, we revealed that for all three predictors and all three measures (1) Bacteria exhibit significantly more disorder than Archaea; (2) plasmid-encoded proteins contain considerably more IDRs than proteins encoded on chromosomes (or whole genomes) in both prokaryote superkingdoms; (3) plasmid proteins are significantly more disordered than chromosomal proteins only in the group of proteins with no COG category assigned; (4) antitoxin proteins in comparison to other proteins, are the most disordered (almost double) in both Bacterial and Archaeal proteomes; (5) plasmidal proteins are more disordered than chromosomal proteins in Bacterial antitoxins and toxin-unclassified proteins, but have almost the same disorder content in toxin proteins.

CONCLUSION: Our results suggest that while disorder content depends on genome and proteome characteristics, it is more influenced by functional engagements than by gene location (on chromosome or plasmid).}, } @article {pmid29699481, year = {2018}, author = {Buetti-Dinh, A and Friedman, R}, title = {Computer simulations of the signalling network in FLT3 +-acute myeloid leukaemia - indications for an optimal dosage of inhibitors against FLT3 and CDK6.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {155}, pmid = {29699481}, issn = {1471-2105}, support = {CAN 2015/387//Cancerfonden/International ; }, mesh = {Apoptosis/drug effects ; Cell Proliferation/drug effects ; *Computer Simulation ; Cyclin-Dependent Kinase 6/*antagonists & inhibitors/genetics ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Leukemia, Myeloid, Acute/drug therapy/genetics/*pathology ; Mutation ; Protein Kinase Inhibitors/*pharmacology/*standards ; Signal Transduction/drug effects ; fms-Like Tyrosine Kinase 3/*antagonists & inhibitors/genetics ; }, abstract = {BACKGROUND: Mutations in the FMS-like tyrosine kinase 3 (FLT3) are associated with uncontrolled cellular functions that contribute to the development of acute myeloid leukaemia (AML). We performed computer simulations of the FLT3-dependent signalling network in order to study the pathways that are involved in AML development and resistance to targeted therapies.

RESULTS: Analysis of the simulations revealed the presence of alternative pathways through phosphoinositide 3 kinase (PI3K) and SH2-containing sequence proteins (SHC), that could overcome inhibition of FLT3. Inhibition of cyclin dependent kinase 6 (CDK6), a related molecular target, was also tested in the simulation but was not found to yield sufficient benefits alone.

CONCLUSIONS: The PI3K pathway provided a basis for resistance to treatments. Alternative signalling pathways could not, however, restore cancer growth signals (proliferation and loss of apoptosis) to the same levels as prior to treatment, which may explain why FLT3 resistance mutations are the most common resistance mechanism. Finally, sensitivity analysis suggested the existence of optimal doses of FLT3 and CDK6 inhibitors in terms of efficacy and toxicity.}, } @article {pmid29699480, year = {2018}, author = {Hofmeister, BT and Schmitz, RJ}, title = {Enhanced JBrowse plugins for epigenomics data visualization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {159}, pmid = {29699480}, issn = {1471-2105}, support = {T32 GM007103/GM/NIGMS NIH HHS/United States ; IOS-1546867//National Science Foundation/International ; T32GM007103/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA/metabolism ; *Databases, Genetic ; *Epigenomics ; Humans ; Nucleotide Motifs/genetics ; RNA/metabolism ; *Software ; }, abstract = {BACKGROUND: New sequencing techniques require new visualization strategies, as is the case for epigenomics data such as DNA base modifications, small non-coding RNAs, and histone modifications.

RESULTS: We present a set of plugins for the genome browser JBrowse that are targeted for epigenomics visualizations. Specifically, we have focused on visualizing DNA base modifications, small non-coding RNAs, stranded read coverage, and sequence motif density. Additionally, we present several plugins for improved user experience such as configurable, high-quality screenshots.

CONCLUSIONS: In visualizing epigenomics with traditional genomics data, we see these plugins improving scientific communication and leading to discoveries within the field of epigenomics.}, } @article {pmid29699476, year = {2018}, author = {Zhang, J and Jia, K and Jia, J and Qian, Y}, title = {An improved approach to infer protein-protein interaction based on a hierarchical vector space model.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {161}, pmid = {29699476}, issn = {1471-2105}, support = {2014DFB30030//China Human Proteome Project/International ; }, mesh = {*Algorithms ; Computational Biology/*methods ; Humans ; *Models, Theoretical ; Protein Interaction Mapping/*methods ; Proteins/*metabolism ; Saccharomyces cerevisiae/*genetics ; Semantics ; *Software ; }, abstract = {BACKGROUND: Comparing and classifying functions of gene products are important in today's biomedical research. The semantic similarity derived from the Gene Ontology (GO) annotation has been regarded as one of the most widely used indicators for protein interaction. Among the various approaches proposed, those based on the vector space model are relatively simple, but their effectiveness is far from satisfying.

RESULTS: We propose a Hierarchical Vector Space Model (HVSM) for computing semantic similarity between different genes or their products, which enhances the basic vector space model by introducing the relation between GO terms. Besides the directly annotated terms, HVSM also takes their ancestors and descendants related by "is_a" and "part_of" relations into account. Moreover, HVSM introduces the concept of a Certainty Factor to calibrate the semantic similarity based on the number of terms annotated to genes. To assess the performance of our method, we applied HVSM to Homo sapiens and Saccharomyces cerevisiae protein-protein interaction datasets. Compared with TCSS, Resnik, and other classic similarity measures, HVSM achieved significant improvement for distinguishing positive from negative protein interactions. We also tested its correlation with sequence, EC, and Pfam similarity using online tool CESSM.

CONCLUSIONS: HVSM showed an improvement of up to 4% compared to TCSS, 8% compared to IntelliGO, 12% compared to basic VSM, 6% compared to Resnik, 8% compared to Lin, 11% compared to Jiang, 8% compared to Schlicker, and 11% compared to SimGIC using AUC scores. CESSM test showed HVSM was comparable to SimGIC, and superior to all other similarity measures in CESSM as well as TCSS. Supplementary information and the software are available at https://github.com/kejia1215/HVSM .}, } @article {pmid29698723, year = {2018}, author = {Singh, S and Das, S and Geeta, R}, title = {A segmental duplication in the common ancestor of Brassicaceae is responsible for the origin of the paralogs KCS6-KCS5, which are not shared with other angiosperms.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {331-345}, doi = {10.1016/j.ympev.2018.04.018}, pmid = {29698723}, issn = {1095-9513}, mesh = {Acyltransferases/*genetics ; Brassicaceae/*genetics ; Chromosomes, Plant/genetics ; *Evolution, Molecular ; Genes, Plant ; Phylogeny ; Polyploidy ; *Segmental Duplications, Genomic ; *Sequence Homology, Amino Acid ; Synteny/genetics ; }, abstract = {Novel morphological structures allowed adaptation to dry conditions in early land plants. The cuticle, one such novelty, plays diverse roles in tolerance to abiotic and biotic stresses and plant development. Cuticular waxes represent a major constituent of the cuticle and are comprised of an assortment of chemicals that include, among others, very long chain fatty acids (VLCFAs). Members of the β-ketoacyl coenzyme A synthases (KCS) gene family code for enzymes that are essential for fatty acid biosynthesis. The gene KCS6 (CUT1) is known to be a key player in the production of VLCFA precursors essential for the synthesis of cuticular waxes in the model plant Arabidopsis thaliana (Brassicaceae). Despite its functional importance, relatively little is known about the evolutionary history of KCS6 or its paralog KCS5 in Brassicaceae or beyond. This lacuna becomes important when we extrapolate understanding of mechanisms gained from the model plant to its containing clades Brassicaceae, flowering plants, or beyond. The Brassicaceae, with several sequenced genomes and a known history of paleoploidy, mesopolyploidy and neopolyploidy, offer a system in which to study the evolution and diversification of the KCS6-KCS5 paralogy. Our phylogenetic analyses across green plants, combined with comparative genomic, microsynteny and evolutionary rates analyses across nine genomes of Brassicaceae, reveal that (1) the KCS6-KCS5 paralogy arose as the result of a large segmental duplication in the ancestral Brassicaceae, (2) the KCS6-KCS5 lineage is represented by a single copy in other flowering plant lineages, (3) the duplicated segments undergo different degrees of retention and loss, and (4) most of the genes in the KCS6 and KCS5 gene blocks (including KCS6 and KCS5 themselves) are under purifying selection. The last also true for most members of the KCS gene family in Brassicaceae, except for KCS8, KCS9 and KCS17, which are under positive selection and may be undergoing functional evolution, meriting further investigation. Overall, our results clearly establish that the ancestral KCS6/5 gene duplicated in the Brassicaceae lineage. It is possible that any specialized functions of KCS5 found in Brassicaceae are either part of a set of KCS6/5 gene functions in the rest of the flowering plants, or unique to Brassicaceae.}, } @article {pmid29698617, year = {2018}, author = {Tadokoro, R and Shikaya, Y and Takahashi, Y}, title = {Wide coverage of the body surface by melanocyte-mediated skin pigmentation.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.04.016}, pmid = {29698617}, issn = {1095-564X}, abstract = {Skin pigmentation is a powerful defense against ultraviolet irradiation. Particularly in humans, the body surface needs to be widely covered by protective pigmentation, and melanocytes, a major lineage of neural crest derivatives, have evolved several maneuvers to transfer melanin pigment to the skin. Recent studies with embryonic melanocytes of chickens and mice have revealed sequential events mediated by melanocytes to maximize the skin coverage by pigmentation. These processes include the migration of melanocyte precursors in the embryo, the microscopic uniform spacing of individual melanocytes, and melanosome transfer from melanocytes to keratinocytes. In particular, in vivo/ex vivo live-imaging techniques of melanosome transfer and a quantitative method to evaluate the distribution patterns of melanocytes have greatly advanced our understanding of how a limited number of cells can implement a maximal coverage of the large surface area of a developing body.}, } @article {pmid29697905, year = {2018}, author = {Wackett, LP}, title = {Protein tagging in environmental microbiology: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1904-1905}, doi = {10.1111/1462-2920.14249}, pmid = {29697905}, issn = {1462-2920}, } @article {pmid29697849, year = {2018}, author = {Saitou, N}, title = {Chance, Finiteness, and History.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1556-1557}, doi = {10.1093/molbev/msy087}, pmid = {29697849}, issn = {1537-1719}, abstract = {Importance of chance, finiteness, and history in evolution is pointed out with special reference to the neutral theory.}, } @article {pmid29697819, year = {2018}, author = {Han, SK and Kim, D and Lee, H and Kim, I and Kim, S}, title = {Divergence of Noncoding Regulatory Elements Explains Gene-Phenotype Differences between Human and Mouse Orthologous Genes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1653-1667}, doi = {10.1093/molbev/msy056}, pmid = {29697819}, issn = {1537-1719}, abstract = {Mice have been widely used as a model organism to investigate human gene-phenotype relationships based on a conjecture that orthologous genes generally perform similar functions and are associated with similar phenotypes. However, phenotypes associated with orthologous genes often turn out to be quite different between human and mouse. Herein, we devised a method to quantitatively compare phenotypes annotations associated with mouse models and human. Using semantic similarity comparisons, we identified orthologous genes with different phenotype annotations, of which the similarity score is on a par with that of random gene pairs. Analysis of sequence evolution and transcriptomic changes revealed that orthologous genes with phenotypic differences are correlated with changes in noncoding regulatory elements and tissue-specific expression profiles rather than changes in protein-coding sequences. To map accurate gene-phenotype relationships using model organisms, we propose that careful consideration of the evolutionary divergence of noncoding regulatory elements and transcriptomic profiles is essential.}, } @article {pmid29697817, year = {2018}, author = {Provataris, P and Meusemann, K and Niehuis, O and Grath, S and Misof, B}, title = {Signatures of DNA Methylation across Insects Suggest Reduced DNA Methylation Levels in Holometabola.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1185-1197}, pmid = {29697817}, issn = {1759-6653}, mesh = {Animals ; Arthropods/genetics ; DNA Methylation/*genetics ; *Evolution, Molecular ; Genome/genetics ; Holometabola/*genetics/metabolism ; Insecta/*genetics/metabolism ; Phylogeny ; Sequence Alignment ; }, abstract = {It has been experimentally shown that DNA methylation is involved in the regulation of gene expression and the silencing of transposable element activity in eukaryotes. The variable levels of DNA methylation among different insect species indicate an evolutionarily flexible role of DNA methylation in insects, which due to a lack of comparative data is not yet well-substantiated. Here, we use computational methods to trace signatures of DNA methylation across insects by analyzing transcriptomic and genomic sequence data from all currently recognized insect orders. We conclude that: 1) a functional methylation system relying exclusively on DNA methyltransferase 1 is widespread across insects. 2) DNA methylation has potentially been lost or extremely reduced in species belonging to springtails (Collembola), flies and relatives (Diptera), and twisted-winged parasites (Strepsiptera). 3) Holometabolous insects display signs of reduced DNA methylation levels in protein-coding sequences compared with hemimetabolous insects. 4) Evolutionarily conserved insect genes associated with housekeeping functions tend to display signs of heavier DNA methylation in comparison to the genomic/transcriptomic background. With this comparative study, we provide the much needed basis for experimental and detailed comparative analyses required to gain a deeper understanding on the evolution and function of DNA methylation in insects.}, } @article {pmid29697195, year = {2018}, author = {Liu, YN and Lu, XX and Ren, A and Shi, L and Zhu, J and Jiang, AL and Yu, HS and Zhao, MW}, title = {Conversion of phosphatidylinositol (PI) to PI4-phosphate (PI4P) and then to PI(4,5)P2 is essential for the cytosolic Ca2+ concentration under heat stress in Ganoderma lucidum.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2456-2468}, doi = {10.1111/1462-2920.14254}, pmid = {29697195}, issn = {1462-2920}, abstract = {How cells drive the phospholipid signal response to heat stress (HS) to maintain cellular homeostasis is a fundamental issue in biology, but the regulatory mechanism of this fundamental process is unclear. Previous quantitative analyses of lipids showed that phosphatidylinositol (PI) accumulates after HS in Ganoderma lucidum, implying the inositol phospholipid signal may be associated with HS signal transduction. Here, we found that the PI-4-kinase and PI-4-phosphate-5-kinase activities are activated and that their lipid products PI-4-phosphate and PI-4,5-bisphosphate are increased under HS. Further experimental results showed that the cytosolic Ca2+ ([Ca2+ ]c) and ganoderic acid (GA) contents induced by HS were decreased when cells were pretreated with Li+ , an inhibitor of inositol monophosphatase, and this decrease could be rescued by PI and PI-4-phosphate. Furthermore, inhibition of PI-4-kinases resulted in a decrease in the Ca2+ and GA contents under HS that could be rescued by PI-4-phosphate but not PI. However, the decrease in the Ca2+ and GA contents by silencing of PI-4-phosphate-5-kinase could not be rescued by PI-4-phosphate. Taken together, our study reveals the essential role of the step converting PI to PI-4-phosphate and then to PI-4,5-bisphosphate in [Ca2+ ]c signalling and GA biosynthesis under HS.}, } @article {pmid29697183, year = {2018}, author = {Spring, S and Bunk, B and Spröer, C and Rohde, M and Klenk, HP}, title = {Genome biology of a novel lineage of planctomycetes widespread in anoxic aquatic environments.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2438-2455}, doi = {10.1111/1462-2920.14253}, pmid = {29697183}, issn = {1462-2920}, abstract = {Anaerobic strains affiliated with a novel order-level lineage of the Phycisphaerae class were retrieved from the suboxic zone of a hypersaline cyanobacterial mat and anoxic sediments of solar salterns. Genome sequences of five isolates were obtained and compared with metagenome-assembled genomes representing related uncultured bacteria from various anoxic aquatic environments. Gene content surveys suggest a strictly fermentative saccharolytic metabolism for members of this lineage, which could be confirmed by the phenotypic characterization of isolates. Genetic analyses indicate that the retrieved isolates do not have a canonical origin of DNA replication, but initiate chromosome replication at alternative sites possibly leading to an accelerated evolution. Further potential factors driving evolution and speciation within this clade include genome reduction by metabolic specialization and rearrangements of the genome by mobile genetic elements, which have a high prevalence in strains from hypersaline sediments and mats. Based on genetic and phenotypic data a distinct group of strictly anaerobic heterotrophic planctomycetes within the Phycisphaerae class could be assigned to a novel order that is represented by the proposed genus Sedimentisphaera gen. nov. comprising two novel species, S. salicampi gen. nov., sp. nov. and S. cyanobacteriorum gen. nov., sp. nov.}, } @article {pmid29697181, year = {2018}, author = {Srivastava, S and Briggs, BR and Dong, H}, title = {Abundance and taxonomic affiliation of molybdenum transport and utilization genes in Tengchong hot springs, China.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2397-2409}, doi = {10.1111/1462-2920.14250}, pmid = {29697181}, issn = {1462-2920}, abstract = {The nitrogen, sulfur and carbon cycles all rely on critical microbial transformations that are carried out by enzymes that require molybdenum (Mo) as a cofactor. Despite Mo importance in these biogeochemical cycles, little information exists about microbial Mo utilization in extreme environments where, due to geochemical conditions, bioavailable Mo may be limited. Using metagenomic data from nine hot springs in Tengchong, Yunnan Province, China, which range in temperature from 42°C to 96°C and pH from 2.3 to 9, the effects of pH, temperature and spring geochemistry on the abundance and taxonomic affiliation of genes related to Mo were studied. Dissolved Mo was only detected at sites with circumneutral pH. However, processes and organisms that require Mo were detected at all sites across all temperature and pH gradients. All sites contained xanthine dehydrogenase, formate dehydrogenase, carbon-monoxide dehydrogenase, nitrate reductase, sulfite oxidase and methionine-sulfoxide reductase despite different community compositions. This suggests that different microbial communities, resulting from different physicochemical conditions, may be performing similar metabolic functions. Furthermore, the abundance and taxonomic diversity of Mo-related annotations increased with higher concentrations of Mo. This study shows that despite geochemical conditions that can limit Mo bioavailability, microbes require Mo for a variety of processes.}, } @article {pmid29696370, year = {2018}, author = {Wang, DY and Wang, Q and Liu, J and Zhang, DC}, title = {Mesoflavibacter profundi sp. nov. Isolated from a Deep-Sea Seamount.}, journal = {Current microbiology}, volume = {75}, number = {9}, pages = {1142-1146}, pmid = {29696370}, issn = {1432-0991}, support = {XDA11030201//the Strategic Priority Research Program of the Chinese Academy of Sciences/ ; No. 2016ASKJ14//the Scientific and Technological Innovation Project Financially Supported by Qingdao National Laboratory for Marine Science and Technology/ ; 2017FY100804//Science & Technology Basic Resources Investigation Program of China/ ; }, mesh = {Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/analysis ; Flavobacteriaceae/*classification/genetics/*physiology ; Genotype ; Pacific Ocean ; Phenotype ; Phospholipids/analysis ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Vitamin K 2 ; }, abstract = {The Gram-stain-negative, rod-shaped, aerobic strain, designated YC1039T, was isolated from a seamount northern Mariana Trench in the tropical western Pacific. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain YC1039T was related to the genus Mesoflavibacter and had highest 16S rRNA gene sequence similarities to Mesoflavibacter sabulilitoris GJMS-9T (98.3%) and Mesoflavibacter zeaxanthinifaciens TD-ZX30T (98.2%). The predominant cellular fatty acids were iso-C15:1 G and iso-C15:0. The polar lipid profile contained phosphatidylethanolamine, two unidentified phospholipids, and 13 unidentified lipids. The respiratory quinone was MK-6. The genomic DNA G+C content of strain YC1039T was 29.8 mol%. On the basis of the evidence presented in this study, strain YC1039T represents a novel species of the genus Mesoflavibacter, for which we propose the name Mesoflavibacter profundi sp. nov. (type strain YC1039T = KACC 19026T = CGMCC 1.16329T).}, } @article {pmid29695870, year = {2018}, author = {Spencer, DT and Drake, T and Briles, TC and Stone, J and Sinclair, LC and Fredrick, C and Li, Q and Westly, D and Ilic, BR and Bluestone, A and Volet, N and Komljenovic, T and Chang, L and Lee, SH and Oh, DY and Suh, MG and Yang, KY and Pfeiffer, MHP and Kippenberg, TJ and Norberg, E and Theogarajan, L and Vahala, K and Newbury, NR and Srinivasan, K and Bowers, JE and Diddams, SA and Papp, SB}, title = {An optical-frequency synthesizer using integrated photonics.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {81-85}, doi = {10.1038/s41586-018-0065-7}, pmid = {29695870}, issn = {1476-4687}, abstract = {Optical-frequency synthesizers, which generate frequency-stable light from a single microwave-frequency reference, are revolutionizing ultrafast science and metrology, but their size, power requirement and cost need to be reduced if they are to be more widely used. Integrated-photonics microchips can be used in high-coherence applications, such as data transmission 1 , highly optimized physical sensors 2 and harnessing quantum states 3 , to lower cost and increase efficiency and portability. Here we describe a method for synthesizing the absolute frequency of a lightwave signal, using integrated photonics to create a phase-coherent microwave-to-optical link. We use a heterogeneously integrated III-V/silicon tunable laser, which is guided by nonlinear frequency combs fabricated on separate silicon chips and pumped by off-chip lasers. The laser frequency output of our optical-frequency synthesizer can be programmed by a microwave clock across 4 terahertz near 1,550 nanometres (the telecommunications C-band) with 1 hertz resolution. Our measurements verify that the output of the synthesizer is exceptionally stable across this region (synthesis error of 7.7 × 10-15 or below). Any application of an optical-frequency source could benefit from the high-precision optical synthesis presented here. Leveraging high-volume semiconductor processing built around advanced materials could allow such low-cost, low-power and compact integrated-photonics devices to be widely used.}, } @article {pmid29695869, year = {2018}, author = {Nguyen, THD and Tam, J and Wu, RA and Greber, BJ and Toso, D and Nogales, E and Collins, K}, title = {Cryo-EM structure of substrate-bound human telomerase holoenzyme.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {190-195}, pmid = {29695869}, issn = {1476-4687}, support = {T32 GM007232/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; GM054198/NH/NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 GM054198/GM/NIGMS NIH HHS/United States ; }, mesh = {Catalytic Domain ; *Cryoelectron Microscopy ; Holoenzymes/chemistry/genetics/metabolism/ultrastructure ; Humans ; Models, Molecular ; Mutation ; Protein Domains ; RNA/chemistry/metabolism/ultrastructure ; Ribonucleoproteins/chemistry/genetics/metabolism/ultrastructure ; Substrate Specificity ; Telomerase/chemistry/genetics/*metabolism/*ultrastructure ; }, abstract = {The enzyme telomerase adds telomeric repeats to chromosome ends to balance the loss of telomeres during genome replication. Telomerase regulation has been implicated in cancer, other human diseases, and ageing, but progress towards clinical manipulation of telomerase has been hampered by the lack of structural data. Here we present the cryo-electron microscopy structure of the substrate-bound human telomerase holoenzyme at subnanometre resolution, showing two flexibly RNA-tethered lobes: the catalytic core with telomerase reverse transcriptase (TERT) and conserved motifs of telomerase RNA (hTR), and an H/ACA ribonucleoprotein (RNP). In the catalytic core, RNA encircles TERT, adopting a well-ordered tertiary structure with surprisingly limited protein-RNA interactions. The H/ACA RNP lobe comprises two sets of heterotetrameric H/ACA proteins and one Cajal body protein, TCAB1, representing a pioneering structure of a large eukaryotic family of ribosome and spliceosome biogenesis factors. Our findings provide a structural framework for understanding human telomerase disease mutations and represent an important step towards telomerase-related clinical therapeutics.}, } @article {pmid29695868, year = {2018}, author = {Sun, C and Benlekbir, S and Venkatakrishnan, P and Wang, Y and Hong, S and Hosler, J and Tajkhorshid, E and Rubinstein, JL and Gennis, RB}, title = {Structure of the alternative complex III in a supercomplex with cytochrome oxidase.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {123-126}, pmid = {29695868}, issn = {1476-4687}, support = {P41 GM103310/GM/NIGMS NIH HHS/United States ; R01 GM123455/GM/NIGMS NIH HHS/United States ; R01 HL016101/HL/NHLBI NIH HHS/United States ; U54 GM087519/GM/NIGMS NIH HHS/United States ; S10 OD019994/OD/NIH HHS/United States ; P41 GM104601/GM/NIGMS NIH HHS/United States ; }, mesh = {*Cryoelectron Microscopy ; Cysteine/chemistry/metabolism ; Cytochrome c Group/*chemistry/metabolism/*ultrastructure ; Cytochromes a/*chemistry/metabolism/*ultrastructure ; Cytochromes a3/*chemistry/metabolism/*ultrastructure ; Electron Transport Complex III/*chemistry/metabolism/*ultrastructure ; Flavobacterium/*enzymology ; Heme/analogs & derivatives/chemistry ; Lipid Bilayers/chemistry/metabolism ; Lipids/chemistry ; Models, Molecular ; Nanostructures/chemistry/ultrastructure ; Oxidation-Reduction ; Protein Subunits/chemistry/metabolism ; }, abstract = {Alternative complex III (ACIII) is a key component of the respiratory and/or photosynthetic electron transport chains of many bacteria1-3. Like complex III (also known as the bc1 complex), ACIII catalyses the oxidation of membrane-bound quinol and the reduction of cytochrome c or an equivalent electron carrier. However, the two complexes have no structural similarity4-7. Although ACIII has eluded structural characterization, several of its subunits are known to be homologous to members of the complex iron-sulfur molybdoenzyme (CISM) superfamily 8 , including the proton pump polysulfide reductase9,10. We isolated the ACIII from Flavobacterium johnsoniae with native lipids using styrene maleic acid copolymer11-14, both as an independent enzyme and as a functional 1:1 supercomplex with an aa3-type cytochrome c oxidase (cyt aa3). We determined the structure of ACIII to 3.4 Å resolution by cryo-electron microscopy and constructed an atomic model for its six subunits. The structure, which contains a [3Fe-4S] cluster, a [4Fe-4S] cluster and six haem c units, shows that ACIII uses known elements from other electron transport complexes arranged in a previously unknown manner. Modelling of the cyt aa3 component of the supercomplex revealed that it is structurally modified to facilitate association with ACIII, illustrating the importance of the supercomplex in this electron transport chain. The structure also resolves two of the subunits of ACIII that are anchored to the lipid bilayer with N-terminal triacylated cysteine residues, an important post-translational modification found in numerous prokaryotic membrane proteins that has not previously been observed structurally in a lipid bilayer.}, } @article {pmid29695867, year = {2018}, author = {Larsen, KP and Mathiharan, YK and Kappel, K and Coey, AT and Chen, DH and Barrero, D and Madigan, L and Puglisi, JD and Skiniotis, G and Puglisi, EV}, title = {Architecture of an HIV-1 reverse transcriptase initiation complex.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {118-122}, pmid = {29695867}, issn = {1476-4687}, support = {P50 GM082545/GM/NIGMS NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; 1S10RR02664701/NH/NIH HHS/United States ; }, mesh = {Base Sequence ; Catalytic Domain ; *Cryoelectron Microscopy ; HIV Reverse Transcriptase/*chemistry/metabolism/*ultrastructure ; HIV-1/*enzymology ; Models, Molecular ; Molecular Conformation ; RNA, Transfer, Lys/chemistry/metabolism/ultrastructure ; Reverse Transcription ; Ribonuclease H/chemistry/metabolism/ultrastructure ; }, abstract = {Reverse transcription of the HIV-1 RNA genome into double-stranded DNA is a central step in viral infection 1 and a common target of antiretroviral drugs 2 . The reaction is catalysed by viral reverse transcriptase (RT)3,4 that is packaged in an infectious virion with two copies of viral genomic RNA 5 each bound to host lysine 3 transfer RNA (tRNALys3), which acts as a primer for initiation of reverse transcription6,7. Upon viral entry into cells, initiation is slow and non-processive compared to elongation8,9. Despite extensive efforts, the structural basis of RT function during initiation has remained a mystery. Here we use cryo-electron microscopy to determine a three-dimensional structure of an HIV-1 RT initiation complex. In our structure, RT is in an inactive polymerase conformation with open fingers and thumb and with the nucleic acid primer-template complex shifted away from the active site. The primer binding site (PBS) helix formed between tRNALys3 and HIV-1 RNA lies in the cleft of RT and is extended by additional pairing interactions. The 5' end of the tRNA refolds and stacks on the PBS to create a long helical structure, while the remaining viral RNA forms two helical stems positioned above the RT active site, with a linker that connects these helices to the RNase H region of the PBS. Our results illustrate how RNA structure in the initiation complex alters RT conformation to decrease activity, highlighting a potential target for drug action.}, } @article {pmid29695866, year = {2018}, author = {Wang, W and Mauleon, R and Hu, Z and Chebotarov, D and Tai, S and Wu, Z and Li, M and Zheng, T and Fuentes, RR and Zhang, F and Mansueto, L and Copetti, D and Sanciangco, M and Palis, KC and Xu, J and Sun, C and Fu, B and Zhang, H and Gao, Y and Zhao, X and Shen, F and Cui, X and Yu, H and Li, Z and Chen, M and Detras, J and Zhou, Y and Zhang, X and Zhao, Y and Kudrna, D and Wang, C and Li, R and Jia, B and Lu, J and He, X and Dong, Z and Xu, J and Li, Y and Wang, M and Shi, J and Li, J and Zhang, D and Lee, S and Hu, W and Poliakov, A and Dubchak, I and Ulat, VJ and Borja, FN and Mendoza, JR and Ali, J and Li, J and Gao, Q and Niu, Y and Yue, Z and Naredo, MEB and Talag, J and Wang, X and Li, J and Fang, X and Yin, Y and Glaszmann, JC and Zhang, J and Li, J and Hamilton, RS and Wing, RA and Ruan, J and Zhang, G and Wei, C and Alexandrov, N and McNally, KL and Li, Z and Leung, H}, title = {Genomic variation in 3,010 diverse accessions of Asian cultivated rice.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {43-49}, doi = {10.1038/s41586-018-0063-9}, pmid = {29695866}, issn = {1476-4687}, mesh = {Asia ; Crops, Agricultural/*classification/*genetics ; Evolution, Molecular ; Genes, Plant/genetics ; *Genetic Variation ; Genetics, Population ; Genome, Plant/*genetics ; Genomics ; Haplotypes ; INDEL Mutation/genetics ; Oryza/*classification/*genetics ; Phylogeny ; Plant Breeding ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {Here we analyse genetic variation, population structure and diversity among 3,010 diverse Asian cultivated rice (Oryza sativa L.) genomes from the 3,000 Rice Genomes Project. Our results are consistent with the five major groups previously recognized, but also suggest several unreported subpopulations that correlate with geographic location. We identified 29 million single nucleotide polymorphisms, 2.4 million small indels and over 90,000 structural variations that contribute to within- and between-population variation. Using pan-genome analyses, we identified more than 10,000 novel full-length protein-coding genes and a high number of presence-absence variations. The complex patterns of introgression observed in domestication genes are consistent with multiple independent rice domestication events. The public availability of data from the 3,000 Rice Genomes Project provides a resource for rice genomics research and breeding.}, } @article {pmid29695865, year = {2018}, author = {Martijn, J and Vosseberg, J and Guy, L and Offre, P and Ettema, TJG}, title = {Deep mitochondrial origin outside the sampled alphaproteobacteria.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {101-105}, doi = {10.1038/s41586-018-0059-5}, pmid = {29695865}, issn = {1476-4687}, mesh = {Alphaproteobacteria/*cytology/*genetics ; Atlantic Ocean ; Genome, Bacterial/genetics ; Genomics ; Metagenome/genetics ; Mitochondria/*genetics/*metabolism ; Pacific Ocean ; *Phylogeny ; }, abstract = {Mitochondria are ATP-generating organelles, the endosymbiotic origin of which was a key event in the evolution of eukaryotic cells 1 . Despite strong phylogenetic evidence that mitochondria had an alphaproteobacterial ancestry 2 , efforts to pinpoint their closest relatives among sampled alphaproteobacteria have generated conflicting results, complicating detailed inferences about the identity and nature of the mitochondrial ancestor. While most studies support the idea that mitochondria evolved from an ancestor related to Rickettsiales3-9, an order that includes several host-associated pathogenic and endosymbiotic lineages10,11, others have suggested that mitochondria evolved from a free-living group12-14. Here we re-evaluate the phylogenetic placement of mitochondria. We used genome-resolved binning of oceanic metagenome datasets and increased the genomic sampling of Alphaproteobacteria with twelve divergent clades, and one clade representing a sister group to all Alphaproteobacteria. Subsequent phylogenomic analyses that specifically address long branch attraction and compositional bias artefacts suggest that mitochondria did not evolve from Rickettsiales or any other currently recognized alphaproteobacterial lineage. Rather, our analyses indicate that mitochondria evolved from a proteobacterial lineage that branched off before the divergence of all sampled alphaproteobacteria. In light of this new result, previous hypotheses on the nature of the mitochondrial ancestor6,15,16 should be re-evaluated.}, } @article {pmid29695864, year = {2018}, author = {Ruan, J and Xia, S and Liu, X and Lieberman, J and Wu, H}, title = {Cryo-EM structure of the gasdermin A3 membrane pore.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {62-67}, pmid = {29695864}, issn = {1476-4687}, support = {DP1 HD087988/HD/NICHD NIH HHS/United States ; R01 AI123265/AI/NIAID NIH HHS/United States ; R01 AI124491/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Membrane/metabolism ; *Cryoelectron Microscopy ; Humans ; Membrane Lipids/metabolism ; Mice ; Models, Molecular ; Mutant Proteins/chemistry/genetics/ultrastructure ; Mutation ; Neoplasm Proteins/chemistry/metabolism/ultrastructure ; Neoplasms/genetics ; Perforin/chemistry/metabolism ; Protein Conformation ; Protein Folding ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Proteins/*chemistry/genetics/metabolism/*ultrastructure ; Structure-Activity Relationship ; }, abstract = {Gasdermins mediate inflammatory cell death after cleavage by caspases or other, unknown enzymes. The cleaved N-terminal fragments bind to acidic membrane lipids to form pores, but the mechanism of pore formation remains unresolved. Here we present the cryo-electron microscopy structures of the 27-fold and 28-fold single-ring pores formed by the N-terminal fragment of mouse GSDMA3 (GSDMA3-NT) at 3.8 and 4.2 Å resolutions, and of a double-ring pore at 4.6 Å resolution. In the 27-fold pore, a 108-stranded anti-parallel β-barrel is formed by two β-hairpins from each subunit capped by a globular domain. We identify a positively charged helix that interacts with the acidic lipid cardiolipin. GSDMA3-NT undergoes radical conformational changes upon membrane insertion to form long, membrane-spanning β-strands. We also observe an unexpected additional symmetric ring of GSDMA3-NT subunits that does not insert into the membrane in the double-ring pore, which may represent a pre-pore state of GSDMA3-NT. These structures provide a basis that explains the activities of several mutant gasdermins, including defective mutants that are associated with cancer.}, } @article {pmid29695863, year = {2018}, author = {Peltzer, N and Darding, M and Montinaro, A and Draber, P and Draberova, H and Kupka, S and Rieser, E and Fisher, A and Hutchinson, C and Taraborrelli, L and Hartwig, T and Lafont, E and Haas, TL and Shimizu, Y and Böiers, C and Sarr, A and Rickard, J and Alvarez-Diaz, S and Ashworth, MT and Beal, A and Enver, T and Bertin, J and Kaiser, W and Strasser, A and Silke, J and Bouillet, P and Walczak, H}, title = {LUBAC is essential for embryogenesis by preventing cell death and enabling haematopoiesis.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {112-117}, pmid = {29695863}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; 096831//Wellcome Trust/United Kingdom ; 158509//Swiss National Science Foundation/Switzerland ; 294880//European Research Council/International ; }, mesh = {Animals ; Carrier Proteins/chemistry/genetics/*metabolism ; Caspase 8/genetics/metabolism ; *Cell Death/genetics ; Embryo Loss/genetics ; *Embryonic Development/genetics ; Endothelial Cells/cytology ; Female ; *Hematopoiesis/genetics ; Mice ; Mice, Inbred C57BL ; Protein Domains ; Protein Kinases/genetics ; Receptor-Interacting Protein Serine-Threonine Kinases/deficiency ; Receptors, Tumor Necrosis Factor, Type I/metabolism ; Signal Transduction ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligases/deficiency/genetics/*metabolism ; }, abstract = {The linear ubiquitin chain assembly complex (LUBAC) is required for optimal gene activation and prevention of cell death upon activation of immune receptors, including TNFR1 1 . Deficiency in the LUBAC components SHARPIN or HOIP in mice results in severe inflammation in adulthood or embryonic lethality, respectively, owing to deregulation of TNFR1-mediated cell death2-8. In humans, deficiency in the third LUBAC component HOIL-1 causes autoimmunity and inflammatory disease, similar to HOIP deficiency, whereas HOIL-1 deficiency in mice was reported to cause no overt phenotype9-11. Here we show, by creating HOIL-1-deficient mice, that HOIL-1 is as essential for LUBAC function as HOIP, albeit for different reasons: whereas HOIP is the catalytically active component of LUBAC, HOIL-1 is required for LUBAC assembly, stability and optimal retention in the TNFR1 signalling complex, thereby preventing aberrant cell death. Both HOIL-1 and HOIP prevent embryonic lethality at mid-gestation by interfering with aberrant TNFR1-mediated endothelial cell death, which only partially depends on RIPK1 kinase activity. Co-deletion of caspase-8 with RIPK3 or MLKL prevents cell death in Hoil-1-/- (also known as Rbck1-/-) embryos, yet only the combined loss of caspase-8 with MLKL results in viable HOIL-1-deficient mice. Notably, triple-knockout Ripk3-/-Casp8-/-Hoil-1-/- embryos die at late gestation owing to haematopoietic defects that are rescued by co-deletion of RIPK1 but not MLKL. Collectively, these results demonstrate that both HOIP and HOIL-1 are essential LUBAC components and are required for embryogenesis by preventing aberrant cell death. Furthermore, they reveal that when LUBAC and caspase-8 are absent, RIPK3 prevents RIPK1 from inducing embryonic lethality by causing defects in fetal haematopoiesis.}, } @article {pmid29695859, year = {2018}, author = {}, title = {The science photos worth seeing.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {408}, doi = {10.1038/d41586-018-04924-5}, pmid = {29695859}, issn = {1476-4687}, mesh = {*Photography ; *Science ; }, } @article {pmid29695858, year = {2018}, author = {}, title = {Climate talks are not enough.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {407-408}, doi = {10.1038/d41586-018-04925-4}, pmid = {29695858}, issn = {1476-4687}, mesh = {*Climate ; *Climate Change ; }, } @article {pmid29695857, year = {2018}, author = {Tollefson, J}, title = {Can the world kick its fossil-fuel addiction fast enough?.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {422-425}, doi = {10.1038/d41586-018-04931-6}, pmid = {29695857}, issn = {1476-4687}, mesh = {Carbon Dioxide/*analysis ; China ; Economic Development/statistics & numerical data ; Electricity ; Fossil Fuels/economics/*statistics & numerical data/*supply & distribution ; Global Warming/legislation & jurisprudence/*prevention & control ; *International Cooperation ; Renewable Energy/*economics/*statistics & numerical data ; Solar Energy/economics/statistics & numerical data ; Time Factors ; }, } @article {pmid29695856, year = {2018}, author = {Leeming, J}, title = {A photo celebration of scientists at work.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {525-527}, doi = {10.1038/d41586-018-04881-z}, pmid = {29695856}, issn = {1476-4687}, mesh = {Awards and Prizes ; *Expeditions ; Photography/*standards ; *Research Personnel ; }, } @article {pmid29695855, year = {2018}, author = {}, title = {Planet-hunter launch, epilepsy drug and NASA's next chief.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {412-413}, doi = {10.1038/d41586-018-04928-1}, pmid = {29695855}, issn = {1476-4687}, } @article {pmid29695854, year = {2018}, author = {}, title = {Challenge anti-Semitism.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {407}, doi = {10.1038/d41586-018-04926-3}, pmid = {29695854}, issn = {1476-4687}, mesh = {Faculty ; Humans ; *Jews ; Periodicals as Topic/ethics ; Prejudice/ethics/legislation & jurisprudence/*prevention & control/trends ; Students ; Universities ; Workforce ; }, } @article {pmid29695853, year = {2018}, author = {Moon, TA}, title = {Geoengineering might speed glacier melt.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {436}, doi = {10.1038/d41586-018-04897-5}, pmid = {29695853}, issn = {1476-4687}, mesh = {Climate ; *Climate Change ; *Ice Cover ; }, } @article {pmid29695852, year = {2018}, author = {Melino, G}, title = {Order must spring from chaos in Italian research.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {436}, doi = {10.1038/d41586-018-04896-6}, pmid = {29695852}, issn = {1476-4687}, mesh = {Italy ; Politics ; *Research ; *Science ; }, } @article {pmid29695851, year = {2018}, author = {Cairns, L}, title = {Cap drug prices with policy - here's how.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {436}, doi = {10.1038/d41586-018-04900-z}, pmid = {29695851}, issn = {1476-4687}, mesh = {*Drug Costs ; Health Policy ; }, } @article {pmid29695850, year = {2018}, author = {Hiney, M}, title = {Make codes for research integrity practical.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {436}, doi = {10.1038/d41586-018-04899-3}, pmid = {29695850}, issn = {1476-4687}, mesh = {Administrative Personnel ; *Codes of Ethics ; *Ethics, Research ; Europe ; Research Personnel/*ethics ; Stakeholder Participation ; }, } @article {pmid29695849, year = {2018}, author = {Miller, TB and Chapman, SC and Aravena, M and Ashby, MLN and Hayward, CC and Vieira, JD and Weiß, A and Babul, A and Béthermin, M and Bradford, CM and Brodwin, M and Carlstrom, JE and Chen, CC and Cunningham, DJM and De Breuck, C and Gonzalez, AH and Greve, TR and Harnett, J and Hezaveh, Y and Lacaille, K and Litke, KC and Ma, J and Malkan, M and Marrone, DP and Morningstar, W and Murphy, EJ and Narayanan, D and Pass, E and Perry, R and Phadke, KA and Rennehan, D and Rotermund, KM and Simpson, J and Spilker, JS and Sreevani, J and Stark, AA and Strandet, ML and Strom, AL}, title = {A massive core for a cluster of galaxies at a redshift of 4.3.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {469-472}, doi = {10.1038/s41586-018-0025-2}, pmid = {29695849}, issn = {1476-4687}, abstract = {Massive galaxy clusters have been found that date to times as early as three billion years after the Big Bang, containing stars that formed at even earlier epochs1-3. The high-redshift progenitors of these galaxy clusters-termed 'protoclusters'-can be identified in cosmological simulations that have the highest overdensities (greater-than-average densities) of dark matter4-6. Protoclusters are expected to contain extremely massive galaxies that can be observed as luminous starbursts 7 . However, recent detections of possible protoclusters hosting such starbursts8-11 do not support the kind of rapid cluster-core formation expected from simulations 12 : the structures observed contain only a handful of starbursting galaxies spread throughout a broad region, with poor evidence for eventual collapse into a protocluster. Here we report observations of carbon monoxide and ionized carbon emission from the source SPT2349-56. We find that this source consists of at least 14 gas-rich galaxies, all lying at redshifts of 4.31. We demonstrate that each of these galaxies is forming stars between 50 and 1,000 times more quickly than our own Milky Way, and that all are located within a projected region that is only around 130 kiloparsecs in diameter. This galaxy surface density is more than ten times the average blank-field value (integrated over all redshifts), and more than 1,000 times the average field volume density. The velocity dispersion (approximately 410 kilometres per second) of these galaxies and the enormous gas and star-formation densities suggest that this system represents the core of a cluster of galaxies that was already at an advanced stage of formation when the Universe was only 1.4 billion years old. A comparison with other known protoclusters at high redshifts shows that SPT2349-56 could be building one of the most massive structures in the Universe today.}, } @article {pmid29695848, year = {2018}, author = {Wendlandt, AE and Vangal, P and Jacobsen, EN}, title = {Quaternary stereocentres via an enantioconvergent catalytic SN1 reaction.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {447-451}, pmid = {29695848}, issn = {1476-4687}, support = {R01 GM043214/GM/NIGMS NIH HHS/United States ; R37 GM043214/GM/NIGMS NIH HHS/United States ; }, mesh = {Carbon/chemistry ; Catalysis ; Chemistry, Organic/*methods ; Hydrogen Bonding ; Kinetics ; Lewis Acids/chemistry ; Stereoisomerism ; Temperature ; }, abstract = {The unimolecular nucleophilic substitution (SN1) mechanism features prominently in every introductory organic chemistry course. In principle, stepwise displacement of a leaving group by a nucleophile via a carbocationic intermediate enables the construction of highly congested carbon centres. However, the intrinsic instability and high reactivity of the carbocationic intermediates make it very difficult to control product distributions and stereoselectivity in reactions that proceed via SN1 pathways. Here we report asymmetric catalysis of an SN1-type reaction mechanism that results in the enantioselective construction of quaternary stereocentres from racemic precursors. The transformation relies on the synergistic action of a chiral hydrogen-bond-donor catalyst with a strong Lewis-acid promoter to mediate the formation of tertiary carbocationic intermediates at low temperature and to achieve high levels of control over reaction enantioselectivity and product distribution. This work provides a foundation for the enantioconvergent synthesis of other fully substituted carbon stereocentres.}, } @article {pmid29695847, year = {2018}, author = {Ockeloen-Korppi, CF and Damskägg, E and Pirkkalainen, JM and Asjad, M and Clerk, AA and Massel, F and Woolley, MJ and Sillanpää, MA}, title = {Stabilized entanglement of massive mechanical oscillators.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {478-482}, doi = {10.1038/s41586-018-0038-x}, pmid = {29695847}, issn = {1476-4687}, abstract = {Quantum entanglement is a phenomenon whereby systems cannot be described independently of each other, even though they may be separated by an arbitrarily large distance 1 . Entanglement has a solid theoretical and experimental foundation and is the key resource behind many emerging quantum technologies, including quantum computation, cryptography and metrology. Entanglement has been demonstrated for microscopic-scale systems, such as those involving photons2-5, ions 6 and electron spins 7 , and more recently in microwave and electromechanical devices8-10. For macroscopic-scale objects8-14, however, it is very vulnerable to environmental disturbances, and the creation and verification of entanglement of the centre-of-mass motion of macroscopic-scale objects remains an outstanding goal. Here we report such an experimental demonstration, with the moving bodies being two massive micromechanical oscillators, each composed of about 10 12 atoms, coupled to a microwave-frequency electromagnetic cavity that is used to create and stabilize the entanglement of their centre-of-mass motion15-17. We infer the existence of entanglement in the steady state by combining measurements of correlated mechanical fluctuations with an analysis of the microwaves emitted from the cavity. Our work qualitatively extends the range of entangled physical systems and has implications for quantum information processing, precision measurements and tests of the limits of quantum mechanics.}, } @article {pmid29695846, year = {2018}, author = {Jamtveit, B and Ben-Zion, Y and Renard, F and Austrheim, H}, title = {Earthquake-induced transformation of the lower crust.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {487-491}, pmid = {29695846}, issn = {1476-4687}, support = {669972//European Research Council/International ; }, abstract = {The structural and metamorphic evolution of the lower crust has direct effects on the lithospheric response to plate tectonic processes involved in orogeny, including subsidence of sedimentary basins, stability of deep mountain roots and extension of high-topography regions. Recent research shows that before orogeny most of the lower crust is dry, impermeable and mechanically strong 1 . During an orogenic event, the evolution of the lower crust is controlled by infiltration of fluids along localized shear or fracture zones. In the Bergen Arcs of Western Norway, shear zones initiate as faults generated by lower-crustal earthquakes. Seismic slip in the dry lower crust requires stresses at a level that can only be sustained over short timescales or local weakening mechanisms. However, normal earthquake activity in the seismogenic zone produces stress pulses that drive aftershocks in the lower crust 2 . Here we show that the volume of lower crust affected by such aftershocks is substantial and that fluid-driven associated metamorphic and structural transformations of the lower crust follow these earthquakes. This provides a 'top-down' effect on crustal geodynamics and connects processes operating at very different timescales.}, } @article {pmid29695845, year = {2018}, author = {Haffner, C and Chelladurai, D and Fedoryshyn, Y and Josten, A and Baeuerle, B and Heni, W and Watanabe, T and Cui, T and Cheng, B and Saha, S and Elder, DL and Dalton, LR and Boltasseva, A and Shalaev, VM and Kinsey, N and Leuthold, J}, title = {Low-loss plasmon-assisted electro-optic modulator.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {483-486}, pmid = {29695845}, issn = {1476-4687}, support = {670478//European Research Council/International ; }, abstract = {For nearly two decades, researchers in the field of plasmonics 1 -which studies the coupling of electromagnetic waves to the motion of free electrons near the surface of a metal 2 -have sought to realize subwavelength optical devices for information technology3-6, sensing7,8, nonlinear optics9,10, optical nanotweezers 11 and biomedical applications 12 . However, the electron motion generates heat through ohmic losses. Although this heat is desirable for some applications such as photo-thermal therapy, it is a disadvantage in plasmonic devices for sensing and information technology 13 and has led to a widespread view that plasmonics is too lossy to be practical. Here we demonstrate that the ohmic losses can be bypassed by using 'resonant switching'. In the proposed approach, light is coupled to the lossy surface plasmon polaritons only in the device's off state (in resonance) in which attenuation is desired, to ensure large extinction ratios between the on and off states and allow subpicosecond switching. In the on state (out of resonance), destructive interference prevents the light from coupling to the lossy plasmonic section of a device. To validate the approach, we fabricated a plasmonic electro-optic ring modulator. The experiments confirm that low on-chip optical losses, operation at over 100 gigahertz, good energy efficiency, low thermal drift and a compact footprint can be combined in a single device. Our result illustrates that plasmonics has the potential to enable fast, compact on-chip sensing and communications technologies.}, } @article {pmid29695844, year = {2018}, author = {Riedinger, R and Wallucks, A and Marinković, I and Löschnauer, C and Aspelmeyer, M and Hong, S and Gröblacher, S}, title = {Remote quantum entanglement between two micromechanical oscillators.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {473-477}, doi = {10.1038/s41586-018-0036-z}, pmid = {29695844}, issn = {1476-4687}, abstract = {Entanglement, an essential feature of quantum theory that allows for inseparable quantum correlations to be shared between distant parties, is a crucial resource for quantum networks 1 . Of particular importance is the ability to distribute entanglement between remote objects that can also serve as quantum memories. This has been previously realized using systems such as warm2,3 and cold atomic vapours4,5, individual atoms 6 and ions7,8, and defects in solid-state systems9-11. Practical communication applications require a combination of several advantageous features, such as a particular operating wavelength, high bandwidth and long memory lifetimes. Here we introduce a purely micromachined solid-state platform in the form of chip-based optomechanical resonators made of nanostructured silicon beams. We create and demonstrate entanglement between two micromechanical oscillators across two chips that are separated by 20 centimetres . The entangled quantum state is distributed by an optical field at a designed wavelength near 1,550 nanometres. Therefore, our system can be directly incorporated in a realistic fibre-optic quantum network operating in the conventional optical telecommunication band. Our results are an important step towards the development of large-area quantum networks based on silicon photonics.}, } @article {pmid29695757, year = {2018}, author = {Trenkmann, M}, title = {A breath-holding adaptation.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {402-403}, doi = {10.1038/s41576-018-0014-1}, pmid = {29695757}, issn = {1471-0064}, } @article {pmid29695630, year = {2018}, author = {Cleves, PA and Strader, ME and Bay, LK and Pringle, JR and Matz, MV}, title = {CRISPR/Cas9-mediated genome editing in a reef-building coral.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5235-5240}, pmid = {29695630}, issn = {1091-6490}, mesh = {Animals ; Base Sequence ; *CRISPR-Cas Systems ; *Coral Reefs ; Fibroblast Growth Factor 1/*antagonists & inhibitors/genetics ; *Gene Editing ; Genome ; Genomics ; Green Fluorescent Proteins/*antagonists & inhibitors/genetics ; Luminescent Proteins/*antagonists & inhibitors/genetics ; *Mutation ; Phenotype ; Sequence Homology ; }, abstract = {Reef-building corals are critically important species that are threatened by anthropogenic stresses including climate change. In attempts to understand corals' responses to stress and other aspects of their biology, numerous genomic and transcriptomic studies have been performed, generating a variety of hypotheses about the roles of particular genes and molecular pathways. However, it has not generally been possible to test these hypotheses rigorously because of the lack of genetic tools for corals. Here, we demonstrate efficient genome editing using the CRISPR/Cas9 system in the coral Acropora millepora We targeted the genes encoding fibroblast growth factor 1a (FGF1a), green fluorescent protein (GFP), and red fluorescent protein (RFP). After microinjecting CRISPR/Cas9 ribonucleoprotein complexes into fertilized eggs, we detected induced mutations in the targeted genes using changes in restriction-fragment length, Sanger sequencing, and high-throughput Illumina sequencing. We observed mutations in ∼50% of individuals screened, and the proportions of wild-type and various mutant gene copies in these individuals indicated that mutation induction continued for at least several cell cycles after injection. Although multiple paralogous genes encoding green fluorescent proteins are present in A. millepora, appropriate design of the guide RNA allowed us to induce mutations simultaneously in more than one paralog. Because A. millepora larvae can be induced to settle and begin colony formation in the laboratory, CRISPR/Cas9-based gene editing should allow rigorous tests of gene function in both larval and adult corals.}, } @article {pmid29695629, year = {2018}, author = {Bercaw, JE}, title = {Jack Halpern (1925-2018): Pioneer of homogeneous catalysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5049-5050}, doi = {10.1073/pnas.1806116115}, pmid = {29695629}, issn = {1091-6490}, } @article {pmid29695628, year = {2018}, author = {Bayless, AM and Zapotocny, RW and Grunwald, DJ and Amundson, KK and Diers, BW and Bent, AF}, title = {An atypical N-ethylmaleimide sensitive factor enables the viability of nematode-resistant Rhg1 soybeans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4512-E4521}, pmid = {29695628}, issn = {1091-6490}, mesh = {Animals ; Disease Resistance/*genetics ; *Gene Expression Regulation, Plant ; Host-Parasite Interactions ; N-Ethylmaleimide-Sensitive Proteins/genetics/*metabolism ; Nematoda/*physiology ; Plant Diseases/parasitology ; Plants, Genetically Modified/genetics/*growth & development/parasitology ; Polymorphism, Single Nucleotide ; Soluble N-Ethylmaleimide-Sensitive Factor Attachment Proteins/genetics/*metabolism ; Soybeans/genetics/*growth & development/parasitology ; }, abstract = {N-ethylmaleimide sensitive factor (NSF) and α-soluble NSF attachment protein (α-SNAP) are essential eukaryotic housekeeping proteins that cooperatively function to sustain vesicular trafficking. The "resistance to Heterodera glycines 1" (Rhg1) locus of soybean (Glycine max) confers resistance to soybean cyst nematode, a highly damaging soybean pest. Rhg1 loci encode repeat copies of atypical α-SNAP proteins that are defective in promoting NSF function and are cytotoxic in certain contexts. Here, we discovered an unusual NSF allele (Rhg1-associated NSF on chromosome 07; NSFRAN07) in Rhg1+ germplasm. NSFRAN07 protein modeling to mammalian NSF/α-SNAP complex structures indicated that at least three of the five NSFRAN07 polymorphisms reside adjacent to the α-SNAP binding interface. NSFRAN07 exhibited stronger in vitro binding with Rhg1 resistance-type α-SNAPs. NSFRAN07 coexpression in planta was more protective against Rhg1 α-SNAP cytotoxicity, relative to WT NSFCh07 Investigation of a previously reported segregation distortion between chromosome 18 Rhg1 and a chromosome 07 interval now known to contain the Glyma.07G195900 NSF gene revealed 100% coinheritance of the NSFRAN07 allele with disease resistance Rhg1 alleles, across 855 soybean accessions and in all examined Rhg1+ progeny from biparental crosses. Additionally, we show that some Rhg1-mediated resistance is associated with depletion of WT α-SNAP abundance via selective loss of WT α-SNAP loci. Hence atypical coevolution of the soybean SNARE-recycling machinery has balanced the acquisition of an otherwise disruptive housekeeping protein, enabling a valuable disease resistance trait. Our findings further indicate that successful engineering of Rhg1-related resistance in plants will require a compatible NSF partner for the resistance-conferring α-SNAP.}, } @article {pmid29695307, year = {2018}, author = {Bowyer, RCE and Jackson, MA and Pallister, T and Skinner, J and Spector, TD and Welch, AA and Steves, CJ}, title = {Use of dietary indices to control for diet in human gut microbiota studies.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {77}, pmid = {29695307}, issn = {2049-2618}, support = {WT081878MA//Wellcome Trust (GB)/International ; CDRF/10/06/2014//Chronic Disease Research Foundation/International ; //Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {Biodiversity ; *Diet ; Feeding Behavior ; *Gastrointestinal Microbiome ; Healthy Diet ; Humans ; Reproducibility of Results ; }, abstract = {BACKGROUND: Environmental factors have a large influence on the composition of the human gut microbiota. One of the most influential and well-studied is host diet. To assess and interpret the impact of non-dietary factors on the gut microbiota, we endeavoured to determine the most appropriate method to summarise community variation attributable to dietary effects. Dietary habits are multidimensional with internal correlations. This complexity can be simplified by using dietary indices that quantify dietary variance in a single measure and offer a means of controlling for diet in microbiota studies. However, to date, the applicability of different dietary indices to gut microbiota studies has not been assessed. Here, we use food frequency questionnaire (FFQ) data from members of the TwinsUK cohort to create three different dietary measures applicable in western-diet populations: The Healthy Eating Index (HEI), the Mediterranean Diet Score (MDS) and the Healthy Food Diversity index (HFD-Index). We validate and compare these three indices to determine which best summarises dietary influences on gut microbiota composition.

RESULTS: All three indices were independently validated using established measures of health, and all were significantly associated with microbiota measures; the HEI had the highest t values in models of alpha diversity measures, and had the highest number of associations with microbial taxa. Beta diversity analyses showed the HEI explained the greatest variance of microbiota composition. In paired tests between twins discordant for dietary index score, the HEI was associated with the greatest variation of taxa and twin dissimilarity.

CONCLUSIONS: We find that the HEI explains the most variance in, and has the strongest association with, gut microbiota composition in a western (UK) population, suggesting that it may be the best summary measure to capture gut microbiota variance attributable to habitual diet in comparable populations.}, } @article {pmid29695294, year = {2018}, author = {Rosenberg, E and Zilber-Rosenberg, I}, title = {The hologenome concept of evolution after 10 years.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {78}, pmid = {29695294}, issn = {2049-2618}, mesh = {Animals ; *Biological Evolution ; *Evolution, Molecular ; Gene Transfer, Horizontal ; Genetic Variation ; Genome/genetics ; Humans ; Microbiota/*genetics ; Plants ; Symbiosis/*physiology ; }, abstract = {The holobiont (host with its endocellular and extracellular microbiome) can function as a distinct biological entity, an additional organismal level to the ones previously considered, on which natural selection operates. The holobiont can function as a whole: anatomically, metabolically, immunologically, developmentally, and during evolution. Consideration of the holobiont with its hologenome as an independent level of selection in evolution has led to a better understanding of underappreciated modes of genetic variation and evolution. The hologenome is comprised of two complimentary parts: host and microbiome genomes. Changes in either genome can result in variations that can be selected for or against. The host genome is highly conserved, and genetic changes within it occur slowly, whereas the microbiome genome is dynamic and can change rapidly in response to the environment by increasing or reducing particular microbes, by acquisition of novel microbes, by horizontal gene transfer, and by mutation. Recent experiments showing that microbiota can play an initial role in speciation have been suggested as an additional mode of enhancing evolution. Some of the genetic variations can be transferred to offspring by a variety of mechanisms. Strain-specific DNA analysis has shown that at least some of the microbiota can be maintained across hundreds of thousands of host generations, implying the existence of a microbial core. We argue that rapid changes in the microbiome genome could allow holobionts to adapt and survive under changing environmental conditions thus providing the time necessary for the host genome to adapt and evolve. As Darwin wrote, "It is not the strongest of the species that survives but the most adaptable".}, } @article {pmid29695286, year = {2018}, author = {Vannier, N and Mony, C and Bittebiere, AK and Michon-Coudouel, S and Biget, M and Vandenkoornhuyse, P}, title = {A microorganisms' journey between plant generations.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {79}, pmid = {29695286}, issn = {2049-2618}, support = {EC2CO program (MIME project)//Centre National de la Recherche Scientifique/International ; PEPS program (MYCOLAND project)//Centre National de la Recherche Scientifique/International ; }, mesh = {Archaea/*classification/genetics/isolation & purification ; Bacteria/*classification/genetics/isolation & purification ; Fungi/*classification/genetics/isolation & purification ; Lamiaceae/*microbiology ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; RNA, Ribosomal, 18S/genetics ; Soil Microbiology ; Symbiosis ; }, abstract = {BACKGROUND: Plants are colonized by a great diversity of microorganisms which form a microbiota and perform additional functions for their host. This microbiota can thus be considered a toolbox enabling plants to buffer local environmental changes, with a positive influence on plant fitness. In this context, the transmission of the microbiota to the progeny represent a way to ensure the presence of beneficial symbionts within the habitat. Examples of such transmission have been mainly described for seed transmission and concern a few pathogenic microorganisms. We investigated the transmission of symbiotic partners to plant progeny within clonal plant network.

METHODS: We used the clonal plant Glechoma hederacea as plant model and forced newly emitted clonal progeny to root in separated pots while controlling the presence of microorganisms. We used an amplicon sequencing approach of 16S and 18S rRNA targeting bacteria/archaea and fungi respectively to describe the root microbiota of mother and clonal-plant offspring.

RESULTS: We demonstrated the vertical transmission of a significant proportion of the mother plants' symbiotic bacteria and fungi to the daughters. Interestingly, archaea were not transmitted to the daughter plants. Transmitted communities had lower richness, suggesting a filtration during transmission. We found that the transmitted pool of microorganisms was similar among daughters, constituting the heritability of a specific cohort of microorganisms, opening a new understanding of the plant holobiont. We also found significant effects of distance to the mother plant and of growth time on the richness of the microbiota transmitted.

CONCLUSIONS: In this clonal plant, microorganisms are transmitted between individuals through connections, thereby ensuring the availability of microbe partners for the newborn plants as well as the dispersion between hosts for the microorganisms. This previously undescribed ecological process allows the dispersal of microorganisms in space and across plant generations. As the vast majority of plants are clonal, this process might be therefore a strong driver of ecosystem functioning and assembly of plant and microorganism communities in a wide range of ecosystems.}, } @article {pmid29695277, year = {2018}, author = {Nkoke, C and Teuwafeu, D and Nkouonlack, C and Abanda, M and Kouam, W and Mapina, A and Makoge, C and Hamadou, B}, title = {Challenges in the management of cardiovascular emergencies in Sub-Saharan Africa: a case report of acute heart failure complicating infective endocarditis in a semi-urban setting in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {259}, pmid = {29695277}, issn = {1756-0500}, mesh = {Adult ; *Aortic Valve ; Cameroon ; Emergency Medical Services/economics/*standards ; Endocarditis/*complications ; Fatal Outcome ; Female ; Heart Failure/*etiology ; Heart Valve Diseases/*complications ; Humans ; }, abstract = {BACKGROUND: Infective endocarditis is a deadly disease if not promptly treated with antibiotics either in association with cardiac surgery or not. Cardiac complications are the most common complications seen in infective endocarditis. Heart failure remains the most common cause of mortality and the most common indication for cardiac surgery in patients with infective endocarditis which is increasingly available in resource limited settings.

CASE PRESENTATION: We report a case of native valve infective endocarditis of the aortic valve in a 27-year old female in a semi-urban setting in Cameroon complicated by severe aortic valve regurgitation and heart failure. She presented with a 2 month history of fever and a 2 weeks history of rapidly worsening shortness of breath. Emergency cardiac surgery was indicated which unfortunately could not be performed leading to the death of the patient.

CONCLUSIONS: In spite of improvement in availability of diagnostic and therapeutic modalities for cardiovascular emergencies, affordability is still a challenge. Universal health coverage is advocated else the ravages of premature mortality from cardiovascular diseases may continue to remain unchecked in Sub-Saharan Africa.}, } @article {pmid29695275, year = {2018}, author = {Yajima, T and Mogi, A and Shimizu, K and Kosaka, T and Nagashima, T and Ohtaki, Y and Obayashi, K and Nakazawa, S and Iijima, M and Yoshida, Y and Hirato, J and Kuwano, H}, title = {Ectopic thymoma in the paratracheal region of the middle mediastinum: a rare case report and literature review.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {256}, pmid = {29695275}, issn = {1756-0500}, mesh = {Aged ; Humans ; Male ; Mediastinum/*diagnostic imaging/pathology/surgery ; Positron-Emission Tomography ; Thoracoscopy ; Thymoma/*diagnostic imaging/pathology/surgery ; Thymus Neoplasms/*diagnostic imaging/pathology/surgery ; }, abstract = {BACKGROUND: Thymomas generally arise from the thymus in the anterior mediastinum. Ectopic thymomas arising in the middle mediastinum are rare. We present a case of a thymoma arising from the ectopic thymic tissue in the right paratracheal region.

CASE PRESENTATION: The patient was a 67-year-old male who underwent an enhanced-computed tomography examination as preoperative staging for colon cancer. A 20-mm nodule in the right paratracheal region was found incidentally. Fluorodeoxyglucose (FDG) accumulation was detected in this solitary nodule by FDG-positron emission tomography, mimicking an enlarged, possibly malignant lymph node. The tumor was removed by thoracoscopic surgery, and a postoperative pathological diagnosis of type AB thymoma was made. Foci of ectopic thymic tissues were found adjacent to the thymoma. The patient was disease-free and without recurrence 2 years postoperatively.

CONCLUSIONS: Including the present case, 13 cases of ectopic paratracheal thymoma have been reported in the English literature, all of which were found on the right side of the paratracheal region. Although ectopic thymomas in the paratracheal region are rare, thymomas may be considered as a differential diagnosis for a paratracheal nodule.}, } @article {pmid29695269, year = {2018}, author = {Giangarra, JE and Barry, SL and Dahlgren, LA and Lanz, OI and Benitez, ME and Werre, SR}, title = {Effect of a single intra-articular injection of bupivacaine on synovial fluid prostaglandin E2 concentrations in normal canine stifles.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {255}, pmid = {29695269}, issn = {1756-0500}, mesh = {Anesthetics, Local/administration & dosage/*adverse effects ; Animals ; Arthrocentesis ; Bupivacaine/administration & dosage/*adverse effects ; Dinoprostone/*metabolism ; Dogs ; Injections, Intra-Articular ; Male ; Stifle/*drug effects ; Synovial Fluid/*drug effects ; Synovitis/*chemically induced/metabolism ; }, abstract = {OBJECTIVE: To identify if synovial fluid prostaglandin E2 increases in response to a single intra-articular dose of bupivacaine in the normal canine stifle.

RESULTS: There were no significant differences in synovial fluid prostaglandin E2 (PGE2) concentrations between treatment groups or over time within bupivacaine or saline groups. Samples requiring ≥ 3 arthrocentesis attempts had significantly higher PGE2 concentrations compared to samples requiring 1 or 2 attempts. Following correction for number of arthrocentesis attempts, PGE2 concentrations were significantly higher than baseline at 24 and 48 h in the bupivacaine group; however there were no significant differences between the bupivacaine and saline groups. In normal dogs, a single bupivacaine injection did not cause significant synovial inflammation, as measured by PGE2 concentrations, compared to saline controls. Future research should minimize aspiration attempts and include evaluation of the synovial response to bupivacaine in clinical cases with joint disease.}, } @article {pmid29695266, year = {2018}, author = {Mishra, AK and Degl'Innocenti, A and Mazzolai, B}, title = {Three-dimensional reconstruction of root shape in the moth orchid Phalaenopsis sp.: a biomimicry methodology for robotic applications.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {258}, pmid = {29695266}, issn = {1756-0500}, mesh = {Biological Mimicry/*physiology ; Imaging, Three-Dimensional/*methods ; Orchidaceae/*anatomy & histology ; Photogrammetry/*methods ; Plant Roots/*anatomy & histology ; Robotics/*methods ; }, abstract = {OBJECTIVE: Within the field of biorobotics, an emerging branch is plant-inspired robotics. Some effort exists in particular towards the production of digging robots that mimic roots; for these, a deeper comprehension of the role of root tip geometry in excavation would be highly desirable. Here we demonstrate a photogrammetry-based pipeline for the production of computer and manufactured replicas of moth orchid root apexes.

RESULTS: Our methods yields faithful root reproductions. This can be used either for quantitative studies aimed at comparing different root morphologies, or directly to implement a particular root shape in a biorobot.}, } @article {pmid29695265, year = {2018}, author = {Mohammed, J and Hounmanou, YMG and Thomsen, LE}, title = {Antimicrobial resistance among clinically relevant bacterial isolates in Accra: a retrospective study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {254}, pmid = {29695265}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects/isolation & purification ; Bodily Secretions/*microbiology ; Body Fluids/*microbiology ; *Drug Resistance, Bacterial ; Escherichia coli/*drug effects/isolation & purification ; Female ; Ghana ; Humans ; Laboratories/*statistics & numerical data ; Laboratories, Hospital/statistics & numerical data ; Male ; Microbial Sensitivity Tests ; Retrospective Studies ; Staphylococcus/*drug effects/isolation & purification ; }, abstract = {OBJECTIVE: The aim of this study was to determine the antimicrobial resistance pattern of bacterial isolates from different specimens at various hospitals and private diagnostic service laboratories in Ghana.

RESULTS: A retrospective data of culture and sensitivity test results from 2016 were extracted from the microbiology record book of six laboratories in Accra, Ghana. The data included type of clinical specimen, sex of patient, name of bacterial isolate and antibiotic resistance profile. A total of 16.6% (n = 10,237) resistant isolates were obtained, however, the proportions of resistant isolates varied significantly between laboratories. High resistance towards tetracycline, ampicillin, cotrimoxazole and cephalosporins, but low towards amoxiclav and aminoglycosides, was observed. This study identified E. coli and Staphylococcus species as the major resistant bacteria from clinical specimen in Accra and the highest prevalence of the isolates was found in urine specimens in all six laboratories (69.1%, n = 204; 52.6%, n = 36; 52.3%, n = 350; 37.9%, n = 298; 53%, n = 219; 62.1%, n = 594) and in female patients (81.4, 50 and 69.5%). Regular surveillance and local susceptibility pattern analysis is extremely important in selecting the most appropriate and effective antibiotic for the treatment of bacterial infections.}, } @article {pmid29695260, year = {2018}, author = {Setsu, R and Asano, K and Numata, N and Tanaka, M and Ibuki, H and Yamamoto, T and Uragami, R and Matsumoto, J and Hirano, Y and Iyo, M and Shimizu, E and Nakazato, M}, title = {A single-arm pilot study of guided self-help treatment based cognitive behavioral therapy for bulimia nervosa in Japanese clinical settings.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {257}, pmid = {29695260}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Bulimia Nervosa/*therapy ; Cognitive Behavioral Therapy/*methods ; Feasibility Studies ; Female ; Humans ; Japan ; *Outcome Assessment (Health Care) ; Pilot Projects ; Self Care/*methods ; Young Adult ; }, abstract = {OBJECTIVE: Guided self-help treatments based on cognitive behavioral therapy (CBT-GSH) are regarded as a first-line effective treatment for bulimia nervosa (BN). With limited application for CBT-GSH in Japanese clinical settings, we conducted a single arm pilot study in order to confirm the acceptability and availability of CBT-GSH in Japan.

RESULTS: 25 women with BN received 16-20 sessions of face-to-face CBT-GSH. Primary outcomes were the completion rate of intervention and abstinence rates from objective bingeing and purging as assessed by the Eating Disorder Examination. Secondary outcomes were other self-report measurements of the frequency of bingeing and purging, and characteristic psychopathologies of eating disorders. Assessments were conducted before CBT as baseline as well as after CBT. 92% (23/25) of the participants completed the CBT sessions. After CBT-GSH, 40% (10/25) of the participants (intention-to-treat) achieved symptom abstinence. The mean binge and purge episodes during the previous 28 days improved from 21.88 to 10.96 (50% reduction) and from 22.44 to 10.88 (52% reduction), each (before CBT-GSH to after CBT-GSH), and the within-group effect sizes were medium (Cohen's d = 0.67, 0.65, each). Our study provided a preliminary evidence about the feasibility of CBT-GSH in Japanese clinical settings for the future. Trial registration This study was registered retrospectively in the national UMIN Clinical Trials Registry on July 10, 2013 (registration ID: UMIN000011120).}, } @article {pmid29695257, year = {2018}, author = {Bornelöv, S and Seroussi, E and Yosefi, S and Benjamini, S and Miyara, S and Ruzal, M and Grabherr, M and Rafati, N and Molin, AM and Pendavis, K and Burgess, SC and Andersson, L and Friedman-Einat, M}, title = {Comparative omics and feeding manipulations in chicken indicate a shift of the endocrine role of visceral fat towards reproduction.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {295}, pmid = {29695257}, issn = {1471-2164}, support = {876-14//Israel Science Foundation/ ; 1294/17//Israel Science Foundation/ ; 0469/14//Chief Scientist of the Israeli Ministry of Agriculture/ ; }, mesh = {Adipokines/genetics ; Animals ; Chickens/*genetics ; Eating ; Female ; Gene Expression Profiling ; Genomics ; Intra-Abdominal Fat/chemistry/*metabolism ; Nicotinamide Phosphoribosyltransferase/genetics ; PTEN Phosphohydrolase/genetics/metabolism ; Phenotype ; Proteomics ; Pulmonary Surfactant-Associated Protein A/genetics ; RNA, Messenger/metabolism ; Reproduction/*genetics ; Sequence Analysis, RNA ; Signal Transduction/genetics ; Transcriptome ; }, abstract = {BACKGROUND: The mammalian adipose tissue plays a central role in energy-balance control, whereas the avian visceral fat hardly expresses leptin, the key adipokine in mammals. Therefore, to assess the endocrine role of adipose tissue in birds, we compared the transcriptome and proteome between two metabolically different types of chickens, broilers and layers, bred towards efficient meat and egg production, respectively.

RESULTS: Broilers and layer hens, grown up to sexual maturation under free-feeding conditions, differed 4.0-fold in weight and 1.6-fold in ovarian-follicle counts, yet the relative accumulation of visceral fat was comparable. RNA-seq and mass-spectrometry (MS) analyses of visceral fat revealed differentially expressed genes between broilers and layers, 1106 at the mRNA level (FDR ≤ 0.05), and 203 at the protein level (P ≤ 0.05). In broilers, Ingenuity Pathway Analysis revealed activation of the PTEN-pathway, and in layers increased response to external signals. The expression pattern of genes encoding fat-secreted proteins in broilers and layers was characterized in the RNA-seq and MS data, as well as by qPCR on visceral fat under free feeding and 24 h-feed deprivation. This characterization was expanded using available RNA-seq data of tissues from red junglefowl, and of visceral fat from broilers of different types. These comparisons revealed expression of new adipokines and secreted proteins (LCAT, LECT2, SERPINE2, SFTP1, ZP1, ZP3, APOV1, VTG1 and VTG2) at the mRNA and/or protein levels, with dynamic gene expression patterns in the selected chicken lines (except for ZP1; FDR/P ≤ 0.05) and feed deprivation (NAMPT, SFTPA1 and ZP3) (P ≤ 0.05). In contrast, some of the most prominent adipokines in mammals, leptin, TNF, IFNG, and IL6 were expressed at a low level (FPKM/RPKM< 1) and did not show differential mRNA expression neither between broiler and layer lines nor between fed vs. feed-deprived chickens.

CONCLUSIONS: Our study revealed that RNA and protein expression in visceral fat changes with selective breeding, suggesting endocrine roles of visceral fat in the selected phenotypes. In comparison to gene expression in visceral fat of mammals, our findings points to a more direct cross talk of the chicken visceral fat with the reproductive system and lower involvement in the regulation of appetite, inflammation and insulin resistance.}, } @article {pmid29695247, year = {2018}, author = {Witt, SH and Frank, J and Gilles, M and Lang, M and Treutlein, J and Streit, F and Wolf, IAC and Peus, V and Scharnholz, B and Send, TS and Heilmann-Heimbach, S and Sivalingam, S and Dukal, H and Strohmaier, J and Sütterlin, M and Arloth, J and Laucht, M and Nöthen, MM and Deuschle, M and Rietschel, M}, title = {Impact on birth weight of maternal smoking throughout pregnancy mediated by DNA methylation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {290}, pmid = {29695247}, issn = {1471-2164}, support = {FOR2107; RI908/11-1//Deutsche Forschungsgemeinschaft/ ; WI3429/3-1//Deutsche Forschungsgemeinschaft/ ; NO246/10-1//Deutsche Forschungsgemeinschaft/ ; 01ZX1314G//Bundesministerium für Bildung und Forschung/ ; 01ZX1314A//Bundesministerium für Bildung und Forschung/ ; }, mesh = {Adult ; Birth Weight/*genetics ; CpG Islands ; *DNA Methylation ; Female ; Fetal Blood/metabolism ; Genome-Wide Association Study ; Humans ; Infant, Newborn ; Integrin beta Chains/genetics ; Male ; Maternal Exposure ; Membrane Proteins/genetics ; Nerve Tissue Proteins/genetics ; Pregnancy ; Proto-Oncogene Proteins c-pim-1/genetics ; *Smoking ; }, abstract = {BACKGROUND: Cigarette smoking has severe adverse health consequences in adults and in the offspring of mothers who smoke during pregnancy. One of the most widely reported effects of smoking during pregnancy is reduced birth weight which is in turn associated with chronic disease in adulthood. Epigenome-wide association studies have revealed that smokers show a characteristic "smoking methylation pattern", and recent authors have proposed that DNA methylation mediates the impact of maternal smoking on birth weight. The aims of the present study were to replicate previous reports that methylation mediates the effect of maternal smoking on birth weight, and for the first time to investigate whether the observed mediation effects are sex-specific in order to account for known sex-specific differences in methylation levels.

METHODS: Methylation levels in the cord blood of 313 newborns were determined using the Illumina HumanMethylation450K Beadchip. A total of 5,527 CpG sites selected on the basis of evidence from the literature were tested. To determine whether the observed association between maternal smoking and birth weight was attributable to methylation, mediation analyses were performed for significant CpG sites. Separate analyses were then performed in males and females.

RESULTS: Following quality control, 282 newborns eventually remained in the analysis. A total of 25 mothers had smoked consistently throughout the pregnancy. The birthweigt of newborns whose mothers had smoked throughout pregnancy was reduced by >200g. After correction for multiple testing, 30 CpGs showed differential methylation in the maternal smoking subgroup including top "smoking methylation pattern" genes AHRR, MYO1G, GFI1, CYP1A1, and CNTNAP2. The effect of maternal smoking on birth weight was partly mediated by the methylation of cg25325512 (PIM1); cg25949550 (CNTNAP2); and cg08699196 (ITGB7). Sex-specific analyses revealed a mediating effect for cg25949550 (CNTNAP2) in male newborns.

CONCLUSION: The present data replicate previous findings that methylation can mediate the effect of maternal smoking on birth weight. The analysis of sex-dependent mediation effects suggests that the sex of the newborn may have an influence. Larger studies are warranted to investigate the role of both the identified differentially methylated loci and the sex of the newborn in mediating the association between maternal smoking during pregnancy and birth weight.}, } @article {pmid29695246, year = {2018}, author = {Ma, Q and Chen, C and Zeng, Z and Zou, Z and Li, H and Zhou, Q and Chen, X and Sun, K and Li, X}, title = {Transcriptomic analysis between self- and cross-pollinated pistils of tea plants (Camellia sinensis).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {289}, pmid = {29695246}, issn = {1471-2164}, support = {31470690//National Natural Science Foundation of China/ ; 31570689//National Natural Science Foundation of China/ ; CARS-19//the China Earmarked Fund for Modern Agro-industry Technology Research System/ ; }, mesh = {Calcium/metabolism ; Calcium Channels/genetics ; Camellia sinensis/*genetics/metabolism ; Flowers/genetics/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Glycosyltransferases/genetics ; Ions/metabolism ; Plant Proteins/genetics ; Pollen/cytology/genetics/growth & development ; Pollination/*genetics ; Potassium/metabolism ; RNA, Plant/chemistry/genetics/metabolism ; Sequence Analysis, RNA ; Signal Transduction/genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Self-incompatibility (SI) is a major barrier that obstructs the breeding process in most horticultural plants including tea plants (Camellia sinensis). The aim of this study was to elucidate the molecular mechanism of SI in tea plants through a high throughput transcriptome analysis.

RESULTS: In this study, the transcriptomes of self- and cross-pollinated pistils of two tea cultivars 'Fudingdabai' and 'Yulv' were compared to elucidate the SI mechanism of tea plants. In addition, the ion components and pollen tube growth in self- and cross-pollinated pistils were investigated. Our results revealed that both cultivars had similar pollen activities and cross-pollination could promote the pollen tube growth. In tea pistils, the highest ion content was potassium (K+), followed by calcium (Ca2+), magnesium (Mg2+) and phosphorus (P5+). Ca2+ content increased after self-pollination but decreased after cross-pollination, while K+ showed reverse trend with Ca2+. A total of 990 and 3 common differentially expressed genes (DEGs) were identified in un-pollinated vs. pollinated pistils and self- vs. cross-pollinated groups after 48 h, respectively. Function annotation indicated that three genes encoding UDP-glycosyltransferase 74B1 (UGT74B1), Mitochondrial calcium uniporter protein 2 (MCU2) and G-type lectin S-receptor-like serine/threonine-protein kinase (G-type RLK) might play important roles during SI process in tea plants.

CONCLUSION: Ca2+ and K+ are important signal for SI in tea plants, and three genes including UGT74B1, MCU2 and G-type RLK play essential roles during SI signal transduction.}, } @article {pmid29695245, year = {2018}, author = {Bihan-Duval, EL and Hennequet-Antier, C and Berri, C and Beauclercq, SA and Bourin, MC and Boulay, M and Demeure, O and Boitard, S}, title = {Identification of genomic regions and candidate genes for chicken meat ultimate pH by combined detection of selection signatures and QTL.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {294}, pmid = {29695245}, issn = {1471-2164}, mesh = {Animals ; Bayes Theorem ; Chickens/*genetics ; *Genome ; Genotype ; Glycogen/metabolism ; Hydrogen-Ion Concentration ; Meat/*analysis ; Muscle, Skeletal/chemistry/metabolism ; Pectoralis Muscles/chemistry/metabolism ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: The understanding of the biological determinism of meat ultimate pH, which is strongly related to muscle glycogen content, is a key point for the control of muscle integrity and meat quality in poultry. In the present study, we took advantage of a unique model of two broiler lines divergently selected for the ultimate pH of the pectoralis major muscle (PM-pHu) in order to decipher the genetic control of this trait. Two complementary approaches were used: detection of selection signatures generated during the first five generations and genome-wide association study for PM-pHu and Sartorius muscle pHu (SART-pHu) at the sixth generation of selection.

RESULTS: Sixty-three genomic regions showed significant signatures of positive selection. Out of the 10 most significant regions (detected by HapFLK or FLK method with a p-value below 1e-6), 4 were detected as soon as the first generation (G1) and were recovered at each of the four following ones (G2-G5). Another four corresponded to a later onset of selection as they were detected only at G5. In total, 33 SNPs, located in 24 QTL regions, were significantly associated with PM-pHu. For SART-pHu, we detected 18 SNPs located in 10 different regions. These results confirmed a polygenic determinism for these traits and highlighted two major QTL: one for PM-pHu on GGA1 (with a Bayes Factor (BF) of 300) and one for SART-pHu on GGA4 (with a BF of 257). Although selection signatures were enriched in QTL for PM-pHu, several QTL with strong effect haven't yet responded to selection, suggesting that the divergence between lines might be further increased.

CONCLUSIONS: A few regions of major interest with significant selection signatures and/or strong association with PM-pHu or SART-pHu were evidenced for the first time in chicken. Their gene content suggests several candidates associated with diseases of glycogen storage in humans. The impact of these candidate genes on meat quality and muscle integrity should be further investigated in chicken.}, } @article {pmid29695243, year = {2018}, author = {Saitou, M and Satta, Y and Gokcumen, O and Ishida, T}, title = {Complex evolution of the GSTM gene family involves sharing of GSTM1 deletion polymorphism in humans and chimpanzees.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {293}, pmid = {29695243}, issn = {1471-2164}, support = {264456//Grant-in-Aid for Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Comparative Genomic Hybridization ; DNA Copy Number Variations ; *Evolution, Molecular ; Gene Deletion ; Gene Duplication ; Genome ; Glucuronosyltransferase/genetics ; Glutathione Transferase/classification/*genetics ; Humans ; Pan troglodytes/*genetics ; Phylogeny ; Polymorphism, Genetic ; }, abstract = {BACKGROUND: The common deletion of the glutathione S-transferase Mu 1 (GSTM1) gene in humans has been shown to be involved in xenobiotic metabolism and associated with bladder cancer. However, the evolution of this deletion has not been investigated.

RESULTS: In this study, we conducted comparative analyses of primate genomes. We demonstrated that the GSTM gene family has evolved through multiple structural variations, involving gene duplications, losses, large inversions and gene conversions. We further showed experimentally that the GSTM1 was polymorphically deleted in both humans and also in chimpanzees, through independent deletion events. To generalize our results, we searched for genic deletions that are polymorphic in both humans and chimpanzees. Consequently, we found only two such deletions among the thousands that we have searched, one of them being the GSTM1 deletion and the other surprisingly being another metabolizing gene, the UGT2B17.

CONCLUSIONS: Overall, our results support the emerging notion that metabolizing gene families, such as the GSTM, NAT, UGT and CYP, have been evolving rapidly through gene duplication and deletion events in primates, leading to complex structural variation within and among species with unknown evolutionary consequences.}, } @article {pmid29695242, year = {2018}, author = {Singh, P and Chung, HJ and Lee, IA and D'Souza, R and Kim, HJ and Hong, ST}, title = {Elucidation of the anti-hyperammonemic mechanism of Lactobacillus amylovorus JBD401 by comparative genomic analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {292}, pmid = {29695242}, issn = {1471-2164}, support = {313040-3//The Technology Development Program for Agriculture and Forestry/ ; }, mesh = {Amino Acids/metabolism ; Ammonia/*blood/metabolism ; Animals ; Bacterial Proteins/genetics ; Comparative Genomic Hybridization ; Evolution, Molecular ; *Genome, Bacterial ; Lactobacillus/*genetics/metabolism ; Lactobacillus acidophilus/genetics ; Metabolic Networks and Pathways/genetics ; Mice ; Ornithine Carbamoyltransferase/genetics ; Phosphotransferases (Carboxyl Group Acceptor)/genetics ; Polyamines/metabolism ; }, abstract = {BACKGROUND: Recent experimental evidence showed that lactobacilli could be used as potential therapeutic agents for hyperammonemia. However, lack of understanding on how lactobacilli reduce blood ammonia levels limits application of lactobacilli to treat hyperammonemia.

RESULTS: We report the finished and annotated genome sequence of L. amylovorus JBD401 (GenBank accession no. CP012389). L. amylovorus JBD401 reducing blood ammonia levels dramatically was identified by high-throughput screening of several thousand probiotic strains both within and across Lactobacillus species in vitro. Administration of L. amylovorus JBD401 to hyperammonemia-induced mice reduced the blood ammonia levels of the mice to the normal range. Genome sequencing showed that L. amylovorus JBD401 had a circular chromosome of 1,946,267 bp with an average GC content of 38.13%. Comparative analysis of the L. amylovorus JBD401 genome with L. acidophilus and L. amylovorus strains showed that L. amylovorus JBD401 possessed genes for ammonia assimilation into various amino acids and polyamines Interestingly, the genome of L. amylovorus JBD401 contained unusually large number of various pseudogenes suggesting an active stage of evolution.

CONCLUSIONS: L. amylovorus JBD401 has genes for assimilation of free ammonia into various amino acids and polyamines which results in removal of free ammonia in intestinal lumen to reduce the blood ammonia levels in the host. This work explains the mechanism of how probiotics reduce blood ammonia levels.}, } @article {pmid29695227, year = {2018}, author = {Han, Z and Ma, X and Wei, M and Zhao, T and Zhan, R and Chen, W}, title = {SSR marker development and intraspecific genetic divergence exploration of Chrysanthemum indicum based on transcriptome analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {291}, pmid = {29695227}, issn = {1471-2164}, support = {2016KYTD02//Regular Institution of Higher Education Innovative Team Project of Guangdong Province/ ; No.81102764//National Natural Science Foundation of China/ ; }, mesh = {Chrysanthemum/*genetics ; Cluster Analysis ; Gene Expression Profiling ; Genes, Plant ; Genetic Markers ; Genetic Variation ; Microsatellite Repeats/*genetics ; Molecular Sequence Annotation ; Ploidies ; RNA, Plant/chemistry/genetics/metabolism ; Sequence Analysis, DNA ; Species Specificity ; *Transcriptome ; }, abstract = {BACKGROUND: Chrysanthemum indicum L., an important ancestral species of the flowering plant chrysanthemum, can be used as medicine and for functional food development. Due to the lack of hereditary information for this species and the difficulty of germplasm identification, we herein provide new genetic insight from the perspective of intraspecific transcriptome comparison and present single sequence repeat (SSR) molecular marker recognition technology.

RESULTS: Through the study of a diploid germplasm (DIWNT) and a tetraploid germplasm (DIWT), the following outcome were obtained. (1) A significant difference in Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) annotations for specific homologous genes was observed using the OrthoMCL method for the identification of homologous gene families between the two cytotypes. Ka/Ks analysis of common, single-copy homologous family members also revealed a greater difference among genes that experienced positive selection than among those experiencing positive selection. (2) Of more practical value, 2575 SSR markers were predicted and partly verified. We used TaxonGap as a visual tool to inspect genotype uniqueness and screen for high-performance molecular loci; we recommend four primers of 65 randomly selected primers with a combined identification success rate of 88.6% as priorities for further development of DNA fingerprinting of C. indicum germplasm.

CONCLUSIONS: The SSR technology based on next-generation sequencing was proved to be successful in the identification of C. indicum germplasms. And the information on the intraspecfic genetic divergence generated by transcriptome comparison deepened the understanding of this complex species' nature.}, } @article {pmid29693660, year = {2018}, author = {}, title = {Make scientific conferences count.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {525}, doi = {10.1038/s41564-018-0158-y}, pmid = {29693660}, issn = {2058-5276}, } @article {pmid29693659, year = {2018}, author = {Chin, CY and Tipton, KA and Farokhyfar, M and Burd, EM and Weiss, DS and Rather, PN}, title = {A high-frequency phenotypic switch links bacterial virulence and environmental survival in Acinetobacter baumannii.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {563-569}, pmid = {29693659}, issn = {2058-5276}, support = {R21 AI115183/AI/NIAID NIH HHS/United States ; I01 BX002788/BX/BLRD VA/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; R21 AI098800/AI/NIAID NIH HHS/United States ; R33 AI098800/AI/NIAID NIH HHS/United States ; I01 BX001725/BX/BLRD VA/United States ; }, abstract = {Antibiotic-resistant infections lead to 700,000 deaths per year worldwide 1 . The roles of phenotypically diverse subpopulations of clonal bacteria in the progression of diseases are unclear. We found that the increasingly pathogenic and antibiotic-resistant pathogen Acinetobacter baumannii harbours a highly virulent subpopulation of cells responsible for disease. This virulent subpopulation possesses a thicker capsule and is resistant to host antimicrobials, which drive its enrichment during infection. Importantly, bacteria harvested from the bloodstream of human patients belong exclusively to this virulent subpopulation. Furthermore, the virulent form exhibits increased resistance to hospital disinfectants and desiccation, indicating a role in environmental persistence and the epidemic spread of disease. We identified a transcriptional 'master regulator' of the switch between avirulent and virulent cells, the overexpression of which abrogates virulence. Furthermore, the overexpression strain is capable of vaccinating mice against lethal challenge. This work highlights a phenotypic subpopulation of bacteria that drastically alters the outcome of infection, and illustrates how knowledge of the regulatory mechanisms controlling such phenotypic switches can be harnessed to attenuate bacteria and develop translational interventions.}, } @article {pmid29693658, year = {2018}, author = {Falony, G and Vieira-Silva, S and Raes, J}, title = {Richness and ecosystem development across faecal snapshots of the gut microbiota.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {526-528}, doi = {10.1038/s41564-018-0143-5}, pmid = {29693658}, issn = {2058-5276}, } @article {pmid29693657, year = {2018}, author = {Weidenmaier, C}, title = {Staphylococcus aureus blocks insulin function.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {533-534}, doi = {10.1038/s41564-018-0153-3}, pmid = {29693657}, issn = {2058-5276}, } @article {pmid29693656, year = {2018}, author = {Bates, PA}, title = {Revising Leishmania's life cycle.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {529-530}, doi = {10.1038/s41564-018-0154-2}, pmid = {29693656}, issn = {2058-5276}, } @article {pmid29693655, year = {2018}, author = {Cohen, JI}, title = {New activities for old antibiotics.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {531-532}, doi = {10.1038/s41564-018-0152-4}, pmid = {29693655}, issn = {2058-5276}, support = {Z01 AI000058-33/NULL/Intramural NIH HHS/United States ; }, } @article {pmid29693544, year = {2018}, author = {Xi, L and Qiao, N and Liu, D and Li, J and Zhang, J and Liu, J}, title = {Pannonibacter carbonis sp. nov., isolated from coal mine water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2042-2047}, doi = {10.1099/ijsem.0.002794}, pmid = {29693544}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; *Coal ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Mining ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {Two bacterial strains were isolated from coal mine water in China. Isolates were facultatively anaerobic, Gram-stain-negative, rod-shaped, motile by means of a single polar flagellum, and they did not produce bacteriochlorophyll α. Cells grew in tryptic soy broth with 0-5.5 % (w/v) NaCl, at 4-55 °C and pH 3.5-10.5. Isolates were positive for catalase, oxidase, urease, Voges-Proskauer test, gelatin hydrolysis and H2S production. Analysis of 16S rRNA gene sequences indicated that the closest relatives of strains Q4.6T and Q2.11 were the type strains Labrenzia suaedae DSM 22153T (97.4 %), Pannonibacter phragmitetus DSM 14782T (96.9 and 97.0 %) and Pannonibacter indicus DSM 23407T (96.8 %). The genomic average nucleotide identity (ANI) value for Q4.6T and Q2.11 was 100 %; however, this value was less than 77.7 % for the type strains P. phragmitetus and P. indicus, and less than 74.0 % for the type strain L. suaedae. The cellular fatty acid profile of strains Q4.6T and Q2.11 consisted primarily of C18 : 1ω7c. The principal quinone of the isolates was Q-10. The polar lipid profile consisted of diphosphatidyl glycerol, phosphatidyl glycerol, phosphatidyl ethanolamine and phosphatidyl choline. On the basis of phylogenetic analysis, genomic ANI analysis, DNA-DNA hybridization results, as well as phenotypic and chemotaxonomic data, strains Q4.6T and Q2.11 are assigned as a novel species within the genus Pannonibacter. The type strain is Pannonibacter carbonis Q4.6T (=CGMCC 1.15703T=KCTC 52466T).}, } @article {pmid29693542, year = {2018}, author = {Kang, H and Cha, I and Kim, H and Joh, K}, title = {Hymenobacter aquatilis sp. nov., isolated from a mesotrophic artificial lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2036-2041}, doi = {10.1099/ijsem.0.002792}, pmid = {29693542}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lakes/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel strain, designated HMF3095T, isolated from freshwater of a mesotrophic artificial lake in the Republic of Korea, was characterized by polyphasic taxonomy. The cells were Gram-stain-negative, aerobic, non-motile, straight rods and formed reddish colonies. Phylogenetic analysis based on its 16S rRNA gene sequence revealed that strain HMF3095T fell within the cluster of the genus Hymenobacterand was most closely related to Hymenobacter seoulensis 16F7GT and Hymenobacter tenuis POB6T (96.7 % sequence similarity). Sequence similarities to all other type strains were 96.3 % or less. The major fatty acids were iso-C15 : 0, C16 : 1ω5c, summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and anteiso-C15 : 0. The major isoprenoid quinone was menaquinone 7. The major polar lipids were phosphatidylethanolamine, three unidentified aminophospholipids and one unidentified phospholipid. The DNA G+C content was 58.9 mol%. On the basis of the evidence presented in this study, strain HMF3095T represents a novel species of the genus Hymenobacter, for which the name Hymenobacter aquatilis sp. nov. is proposed. The type strain is HMF3095T (=KCTC 52398T=NBRC 112669T).}, } @article {pmid29693444, year = {2018}, author = {Haney, SD and Siepielski, AM}, title = {Tipping Points in Resource Abundance Drive Irreversible Changes in Community Structure.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {668-675}, doi = {10.1086/697045}, pmid = {29693444}, issn = {1537-5323}, abstract = {Global climate change has made what were seemingly extraordinary environmental conditions, such as prolonged droughts, commonplace. One consequence of extreme environmental change is concomitant changes in resource abundance. How will such extreme resource changes impact biodiversity? We developed a trait-based consumer-resource model to examine how resource abundance affects the potential for adaptive evolution and coexistence among competitors. We found that moderate changes in resource abundance have little effect on trait evolution. However, when resource scarcities were sufficiently extreme, a critical transition-a tipping point-occurred, which caused consumer traits to diverge and restructured the community in a way that outlasted the scarcity. Therefore, even though traits can evolve in response to minor resource fluctuations, large environmental shifts may be necessary for producing long-lasting impacts on community structure. These results may also help to illuminate patterns of stasis frequently observed in nature, despite the considerable evidence demonstrating rapid evolutionary change.}, } @article {pmid29693443, year = {2018}, author = {Sheldon, KS and Huey, RB and Kaspari, M and Sanders, NJ}, title = {Fifty Years of Mountain Passes: A Perspective on Dan Janzen's Classic Article.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {553-565}, doi = {10.1086/697046}, pmid = {29693443}, issn = {1537-5323}, abstract = {In 1967, Dan Janzen published "Why Mountain Passes Are Higher in the Tropics" in The American Naturalist. Janzen's seminal article has captured the attention of generations of biologists and continues to inspire theoretical and empirical work. The underlying assumptions and derived predictions are broadly synthetic and widely applicable. Consequently, Janzen's "seasonality hypothesis" has proven relevant to physiology, climate change, ecology, and evolution. To celebrate the fiftieth anniversary of this highly influential article, we highlight the past, present, and future of this work and include a unique historical perspective from Janzen himself.}, } @article {pmid29693442, year = {2018}, author = {Baliga, VB and Mehta, RS}, title = {Phylo-Allometric Analyses Showcase the Interplay between Life-History Patterns and Phenotypic Convergence in Cleaner Wrasses.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {E129-E143}, doi = {10.1086/697047}, pmid = {29693442}, issn = {1537-5323}, abstract = {Phenotypic convergence is a macroevolutionary pattern that need not be consistent across life history. Ontogenetic transitions in dietary specialization clearly illustrate the dynamics of ecological selection as organisms grow. The extent of phenotypic convergence among taxa that share a similar ecological niche may therefore vary ontogenetically. Because ontogenetic processes have been shown to evolve, phylogenetic comparative methods can be useful in examining how the scaling of traits relates to ecology. Cleaning, a behavior in which taxa consume ectoparasites off clientele, is well represented among wrasses (Labridae). Nearly three-fourths of labrids that clean do so predominately as juveniles, transitioning away as adults. We examine the scaling patterns of 33 labrid species to understand how life-history patterns of cleaning relate to ontogenetic patterns of phenotypic convergence. We find that as juveniles, cleaners exhibit convergence in body and cranial traits that enhance ectoparasitivory. We then find that taxa that transition away from cleaning exhibit ontogenetic trajectories that are distinct from those of other wrasses. Obligate and facultative species that continue to clean over ontogeny, however, maintain characteristics that are conducive to cleaning. Collectively, we find that life-history patterns of cleaning behavior are concordant with ontogenetic patterns in phenotype in wrasses.}, } @article {pmid29693441, year = {2018}, author = {Edwards, KF and Steward, GF}, title = {Host Traits Drive Viral Life Histories across Phytoplankton Viruses.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {566-581}, doi = {10.1086/696849}, pmid = {29693441}, issn = {1537-5323}, abstract = {Viruses are integral to ecological and evolutionary processes, but we have a poor understanding of what drives variation in key traits across diverse viruses. For lytic viruses, burst size, latent period, and genome size are primary characteristics controlling host-virus dynamics. Here we synthesize data on these traits for 75 strains of phytoplankton viruses, which play an important role in global biogeochemistry. We find that primary traits of the host (genome size, growth rate) explain 40%-50% of variation in burst size and latent period. Specifically, burst size and latent period both exhibit saturating relationships versus the host∶virus genome size ratio, with both traits increasing at low genome size ratios while showing no relationship at high size ratios. In addition, latent period declines as host growth rate increases. We analyze a model of latent period evolution to explore mechanisms that could cause these patterns. The model predicts that burst size may often be set by the host genomic resources available for viral construction, while latent period evolves to permit this maximal burst size, modulated by host metabolic rate. These results suggest that general mechanisms may underlie the evolution of diverse viruses. Future extensions of this work could help explain viral regulation of host populations, viral influence on community structure and diversity, and viral roles in biogeochemical cycles.}, } @article {pmid29693440, year = {2018}, author = {Tibbetts, EA and Injaian, A and Sheehan, MJ and Desjardins, N}, title = {Intraspecific Variation in Learning: Worker Wasps Are Less Able to Learn and Remember Individual Conspecific Faces than Queen Wasps.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {595-603}, doi = {10.1086/696848}, pmid = {29693440}, issn = {1537-5323}, abstract = {Research on individual recognition often focuses on species-typical recognition abilities rather than assessing intraspecific variation in recognition. As individual recognition is cognitively costly, the capacity for recognition may vary within species. We test how individual face recognition differs between nest-founding queens (foundresses) and workers in Polistes fuscatus paper wasps. Individual recognition mediates dominance interactions among foundresses. Three previously published experiments have shown that foundresses (1) benefit by advertising their identity with distinctive facial patterns that facilitate recognition, (2) have robust memories of individuals, and (3) rapidly learn to distinguish between face images. Like foundresses, workers have variable facial patterns and are capable of individual recognition. However, worker dominance interactions are muted. Therefore, individual recognition may be less important for workers than for foundresses. We find that (1) workers with unique faces receive amounts of aggression similar to those of workers with common faces, indicating that wasps do not benefit from advertising their individual identity with a unique appearance; (2) workers lack robust memories for individuals, as they cannot remember unique conspecifics after a 6-day separation; and (3) workers learn to distinguish between facial images more slowly than foundresses during training. The recognition differences between foundresses and workers are notable because Polistes lack discrete castes; foundresses and workers are morphologically similar, and workers can take over as queens. Overall, social benefits and receiver capacity for individual recognition are surprisingly plastic.}, } @article {pmid29693439, year = {2018}, author = {Wessinger, CA and Kelly, JK}, title = {Selfing Can Facilitate Transitions between Pollination Syndromes.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {582-594}, doi = {10.1086/696856}, pmid = {29693439}, issn = {1537-5323}, abstract = {Pollinator-mediated selection on plants can favor transitions to a new pollinator depending on the relative abundances and efficiencies of pollinators present in the community. A frequently observed example is the transition from bee pollination to hummingbird pollination. We present a population genetic model that examines whether the ability to inbreed can influence evolutionary change in traits that underlie pollinator attraction. We find that a transition to a more efficient but less abundant pollinator is favored under a broadened set of ecological conditions if plants are capable of delayed selfing rather than obligately outcrossing. Delayed selfing allows plants carrying an allele that attracts the novel pollinator to reproduce even when this pollinator is rare, providing reproductive assurance. In addition, delayed selfing weakens the effects of Haldane's sieve by increasing the fixation probability for recessive alleles that confer adaptation to the new pollinator. Our model provides novel insight into the paradoxical abundance of recessive mutations in adaptation to hummingbird attraction. It further predicts that transitions to efficient but less abundant pollinators (such as hummingbirds in certain communities) should disproportionately occur in self-compatible lineages. Currently available mating system data sets are consistent with this prediction, and we suggest future areas of research that will enable a rigorous test of this theory.}, } @article {pmid29693438, year = {2018}, author = {Hovanes, KA and Harms, KE and Gagnon, PR and Myers, JA and Elderd, BD}, title = {Overdispersed Spatial Patterning of Dominant Bunchgrasses in Southeastern Pine Savannas.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {658-667}, doi = {10.1086/696834}, pmid = {29693438}, issn = {1537-5323}, abstract = {Spatial patterning is a key natural history attribute of sessile organisms that frequently emerges from and dictates potential for interactions among organisms. We tested whether bunchgrasses, the dominant plant functional group in longleaf pine savanna groundcover communities, are nonrandomly patterned by characterizing the spatial dispersion of three bunchgrass species across six sites in Louisiana and Florida. We mapped bunchgrass tussocks of >5.0 cm basal diameter in three [Formula: see text] plots at each site. We modeled tussocks as two-dimensional objects to analyze their spatial relationships while preserving sizes and shapes of individual tussocks. Tussocks were overdispersed (more regularly spaced than random) for all species and sites at the local interaction scale (<0.3 m). This general pattern likely arises from a tussock-centered, distance-dependent mechanism, for example, intertussock competition. Nonrandom spatial patterns of dominant species have implications for community assembly and ecosystem function in tussock-dominated grasslands and savannas, including those characterized by extreme biodiversity.}, } @article {pmid29693437, year = {2018}, author = {Germain, RR and Arcese, P and Reid, JM}, title = {The Consequences of Polyandry for Sibship Structures, Distributions of Relationships and Relatedness, and Potential for Inbreeding in a Wild Population.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {638-657}, doi = {10.1086/696855}, pmid = {29693437}, issn = {1537-5323}, abstract = {The evolutionary benefits of simultaneous polyandry (female multiple mating within a single reproductive event) remain elusive. One potential benefit could arise if polyandry alters sibship structures and consequent relationships and relatedness among females' descendants, thereby intrinsically reducing future inbreeding risk (the indirect inbreeding avoidance hypothesis). However such effects have not been quantified in naturally complex mating systems that also encompass iteroparity, overlapping generations, sequential polyandry, and polygyny. We used long-term social and genetic pedigree data from song sparrows (Melospiza melodia) to quantify cross-generational consequences of simultaneous polyandry for offspring sibship structures and distributions of relationships and relatedness among possible mates. Simultaneous polyandry decreased full sibships and increased half-sibships, on average, but such effects varied among females and were smaller than would occur in the absence of sequential polyandry or polygyny. Further, while simultaneous polyandry decreased the overall frequencies of possible matings among adult full sibs, it increased the frequencies of possible matings among adult half-sibs and more distant relatives. These results imply that the intrinsic consequences of simultaneous polyandry for inbreeding risk could cause weak indirect selection on polyandry, but the magnitude and direction of such effects will depend on complex interactions with other mating system components and the form of inbreeding depression.}, } @article {pmid29693436, year = {2018}, author = {Lion, S}, title = {Class Structure, Demography, and Selection: Reproductive-Value Weighting in Nonequilibrium, Polymorphic Populations.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {620-637}, doi = {10.1086/696976}, pmid = {29693436}, issn = {1537-5323}, abstract = {In natural populations, individuals of a given genotype may belong to different classes. Such classes can represent different age groups, developmental stages, or habitats. Class structure has important evolutionary consequences because the fitness of individuals with the same genetic background may vary depending on their class. As a result, demographic transitions between classes can cause fluctuations in the trait mean that need to be removed when estimating selection on a trait. Intrinsic differences between classes are classically taken into account by weighting individuals by class-specific reproductive values, defined as the relative contribution of individuals in a given class to the future of the population. These reproductive values are generally constant weights calculated from a constant projection matrix. Here, I show for large populations and clonal reproduction that reproductive values can be defined as time-dependent weights satisfying dynamical demographic equations that depend only on the average between-class transition rates over all genotypes. Using these time-dependent demographic reproductive values yields a simple Price equation where the nonselective effects of between-class transitions are removed from the dynamics of the trait. This generalizes previous theory to a large class of ecological scenarios, taking into account density dependence, ecological feedbacks, arbitrary strength of selection, and arbitrary trait distributions. I discuss the role of reproductive values for prospective and retrospective analyses of the dynamics of phenotypic traits.}, } @article {pmid29693435, year = {2018}, author = {Ramakers, JJC and Cobben, MMP and Bijma, P and Reed, TE and Visser, ME and Gienapp, P}, title = {Maternal Effects in a Wild Songbird Are Environmentally Plastic but Only Marginally Alter the Rate of Adaptation.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {E144-E158}, doi = {10.1086/696847}, pmid = {29693435}, issn = {1537-5323}, abstract = {Despite ample evidence for the presence of maternal effects (MEs) in a variety of traits and strong theoretical indications for their evolutionary consequences, empirical evidence to what extent MEs can influence evolutionary responses to selection remains ambiguous. We tested the degree to which MEs can alter the rate of adaptation of a key life-history trait, clutch size, using an individual-based model approach parameterized with experimental data from a long-term study of great tits (Parus major). We modeled two types of MEs: (i) an environmentally plastic ME, in which the relationship between maternal and offspring clutch size depended on the maternal environment via offspring condition, and (ii) a fixed ME, in which this relationship was constant. Although both types of ME affected the rate of adaptation following an abrupt environmental shift, the overall effects were small. We conclude that evolutionary consequences of MEs are modest at best in our study system, at least for the trait and the particular type of ME we considered here. A closer link between theoretical and empirical work on MEs would hence be useful to obtain accurate predictions about the evolutionary consequences of MEs more generally.}, } @article {pmid29693434, year = {2018}, author = {Rollinson, N and Rowe, L}, title = {Oxygen Limitation at the Larval Stage and the Evolution of Maternal Investment per Offspring in Aquatic Environments.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {604-619}, doi = {10.1086/696857}, pmid = {29693434}, issn = {1537-5323}, abstract = {Oxygen limitation and surface area to volume relationships of the egg were long thought to constrain egg size in aquatic environments, but more recent evidence indicates that egg size per se does not influence oxygen availability to embryos. Here, we suggest that investment per offspring is nevertheless constrained in aquatic anamniotes by virtue of oxygen transport in free-living larvae. Drawing on the well-supported assumption that oxygen limitation is relatively pronounced in aquatic versus terrestrial environments and that oxygen limitation is particularly severe in warm aquatic environments, we employ comparative methods in the Amphibia to investigate this problem. Across hundreds of species and two major amphibian clades, the slope of species mean egg diameter over habitat temperature is negative for species with aquatic larvae but is positive or neutral for species featuring terrestrial eggs and no larvae. Yet across species with aquatic larvae, the negative slope of egg diameter over temperature is similar whether eggs are laid terrestrially or aquatically, consistent with an oxygen constraint arising at the larval stage. Finally, egg size declines more strongly with temperature for species that cannot breathe aerially before metamorphosis compared with those that can. Our results suggest that oxygen transport in larvae (not eggs) constrains investment per offspring. This study further extends the generality of temperature-dependent oxygen limitation as a mechanism driving the temperature-size rule in aquatic systems.}, } @article {pmid29693433, year = {2018}, author = {Patrick, CJ and Brown, BL}, title = {Species Pool Functional Diversity Plays a Hidden Role in Generating β-Diversity.}, journal = {The American naturalist}, volume = {191}, number = {5}, pages = {E159-E170}, doi = {10.1086/696978}, pmid = {29693433}, issn = {1537-5323}, abstract = {Functional trait diversity is used as a way to infer mechanistic processes that drive community assembly. While functional diversity within communities is often viewed as a response variable, here we present and test a framework for how functional diversity among taxa in the regional species pool drives the assembly of communities among habitats. We predicted that species pool functional diversity should work with environmental heterogeneity to drive β-diversity. We tested these predictions by modeling empirical patterns in invertebrate communities from 570 streams in 52 watersheds. Our analysis of the field data provided strong support for the inclusion of both functional diversity and environmental heterogeneity in the models, and our predictions were supported when the community was analyzed all together. However, analyses within individual functional feeding guilds revealed strong context dependency in the relative importance of functional diversity, γ-richness, and environmental heterogeneity to β-diversity. We interpret the results to mean that functional diversity can play an important role in driving β-diversity; however, within guilds the nature of interspecific interactions and species pool size complicate the relationship. Future research should test this conceptual model across different ecosystems and in experimental settings using metacommunity mesocosms to enhance our understanding of the role that functional variation plays in generating spatial biodiversity patterns.}, } @article {pmid29693197, year = {2018}, author = {Corti Monzón, G and Nisenbaum, M and Herrera Seitz, MK and Murialdo, SE}, title = {New Findings on Aromatic Compounds' Degradation and Their Metabolic Pathways, the Biosurfactant Production and Motility of the Halophilic Bacterium Halomonas sp. KHS3.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1108-1118}, pmid = {29693197}, issn = {1432-0991}, support = {PICT 2014-1567//Fondo para la Investigación Científica y Tecnológica/ ; PIT-BA-2016, 1443/16, 1266/15//Comisión de Investigaciones Científicas/ ; 15/G426 ING432/15, 15/G433 ING439/15//Universidad Nacional de Mar del Plata/ ; }, mesh = {Adipates/*metabolism ; Argentina ; Benzoic Acid/*metabolism ; Biodegradation, Environmental ; DNA, Bacterial/genetics ; Halomonas/enzymology/*genetics/*metabolism ; Parabens/*metabolism ; Polycyclic Aromatic Hydrocarbons/*metabolism ; Salinity ; Sodium Chloride/analysis ; }, abstract = {The study of the aromatic compounds' degrading ability by halophilic bacteria became an interesting research topic, because of the increasing use of halophiles in bioremediation of saline habitats and effluents. In this work, we focused on the study of aromatic compounds' degradation potential of Halomonas sp. KHS3, a moderately halophilic bacterium isolated from hydrocarbon-contaminated seawater of the Mar del Plata harbour. We demonstrated that H. sp. KHS3 is able to grow using different monoaromatic (salicylic acid, benzoic acid, 4-hydroxybenzoic acid, phthalate) and polyaromatic (naphthalene, fluorene, and phenanthrene) substrates. The ability to degrade benzoic acid and 4-hydroxybenzoic acid was analytically corroborated, and Monod kinetic parameters and yield coefficients for degradation were estimated. Strategies that may enhance substrate bioavailability such as surfactant production and chemotactic responses toward aromatic compounds were confirmed. Genomic sequence analysis of this strain allowed us to identify several genes putatively related to the metabolism of aromatic compounds, being the catechol and protocatechuate branches of β-ketoadipate pathway completely represented. These features suggest that the broad-spectrum xenobiotic degrader H. sp. KHS3 could be employed as a useful biotechnological tool for the cleanup of aromatic compounds-polluted saline habitats or effluents.}, } @article {pmid29693196, year = {2018}, author = {Li, C and Wei, X and Gao, L and Chen, W and Liu, T and Liu, B}, title = {iTRAQ-Based Proteomic Analysis of Wheat Bunt Fungi Tilletia controversa, T. caries, and T. foetida.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1103-1107}, pmid = {29693196}, issn = {1432-0991}, support = {31571965//National Natural Science Foundation of China/ ; }, mesh = {Basidiomycota/*genetics/growth & development/metabolism ; DNA Primers/genetics ; DNA, Fungal/genetics ; Fungal Proteins/*analysis/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Fungal/*genetics ; Plant Diseases/*microbiology ; Proteomics/*methods ; Triticum/*microbiology ; }, abstract = {This is the first study of proteomics of wheat bunt fungi Tilletia controversa (TCK), T. caries (TCT), and T. foetida (TFL) using the iTRAQ technique. Based on the relative quantities of specific proteins between each two pathogens, we found 50 up-regulated and 80 down-regulated protein genes in TCK compared to TFL, 62 up-regulated and 82 down-regulated protein genes in TCT compared to TFL, 47 up-regulated and 30 down-regulated protein genes in TCK compared to TCT, and there were 1 protein of up-regulated and 4 proteins of down-regulated in the three pairs. These protein data could be of great value for exploring the key proteins which play an important role in the interactions of these pathogens with their host. Some of them could be valuable for differentiating the three pathogens with monoclonal antibodies produced by the specific proteins and may enable in-site detection of the pathogens and performing routine monitoring as a diagnostic assay in wheat shipments.}, } @article {pmid29693195, year = {2018}, author = {Schu, MG and Schrallhammer, M}, title = {Cultivation Conditions Can Cause a Shift from Mutualistic to Parasitic Behavior in the Symbiosis Between Paramecium and Its Bacterial Symbiont Caedibacter taeniospiralis.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1099-1102}, pmid = {29693195}, issn = {1432-0991}, mesh = {Culture Media/*analysis ; Gammaproteobacteria/*growth & development/*metabolism ; Paramecium/*microbiology ; Symbiosis/*physiology ; }, abstract = {Caedibacter taeniospiralis is an obligate bacterial symbiont living in the cytoplasm of the ciliate Paramecium tetraurelia. Different studies analyzing the effect of this symbiont on its host's growth and maximal cell density arrive at contradicting conclusions, labeling it as either a parasite or a mutualist. We address the question whether extrinsic factors such as medium and food organism are responsible for the opposing results. Thus, we performed fitness assays comparing previously applied cultivation conditions. By confirming the dependency of the parasitic and mutualistic behavior of C. taeniospiralis on the cultivation conditions of its host P. tetraurelia, we demonstrate the context-dependent impact on host fitness of this bacterium.}, } @article {pmid29692897, year = {2018}, author = {Waynforth, D}, title = {Unstable employment and health in middle age in the longitudinal 1970 British Birth Cohort Study.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {92-99}, pmid = {29692897}, issn = {2050-6201}, abstract = {Background and objectives: Jobs for life have become increasingly rare in industrialized economies, and have been replaced by shorter-term employment contracts and freelancing. This labour market change is likely to be accompanied by physiological changes in individuals who have experienced little job stability. Evolved responses to increased environmental instability or stochasticity include increased fat deposition and fight-or-flight responses, such as glucose mobilization and increased blood pressure. These responses may have evolved by natural selection as beneficial to individuals in the short-term, but are damaging in the longer term.

Methodology: This study tested whether job losses experienced between ages 30 and 42 are associated with increased body weight, hypertension and diabetes diagnosis in the 1970 British Birth Cohort, which consists of all registered births in a one-week period in April 1970.

Results: Each job loss experienced increased the odds of developing diabetes by 1.39 times (CI 1.08-1.80), and of hypertension by 1.28 times (CI 1.07-1.53). Another economic variable, higher personal debt, was associated with all three of these health outcomes: every £100 000 of debt roughly doubled the odds of gaining at least 5 kg between ages 30 and 42.

Conclusions and implications: These associations between job loss and health-risk factors suggest that our changing economy results in increases in the prevalence of risk factors for cardiovascular disease. At a broader level, they are consistent with evolutionary understandings of environmental stochasticity, and are a reminder that economic policy is also health policy.}, } @article {pmid29692414, year = {2018}, author = {Eisenberg, E and Levanon, EY}, title = {A-to-I RNA editing - immune protector and transcriptome diversifier.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {8}, pages = {473-490}, doi = {10.1038/s41576-018-0006-1}, pmid = {29692414}, issn = {1471-0064}, abstract = {Modifications of RNA affect its function and stability. RNA editing is unique among these modifications because it not only alters the cellular fate of RNA molecules but also alters their sequence relative to the genome. The most common type of RNA editing is A-to-I editing by double-stranded RNA-specific adenosine deaminase (ADAR) enzymes. Recent transcriptomic studies have identified a number of 'recoding' sites at which A-to-I editing results in non-synonymous substitutions in protein-coding sequences. Many of these recoding sites are conserved within (but not usually across) lineages, are under positive selection and have functional and evolutionary importance. However, systematic mapping of the editome across the animal kingdom has revealed that most A-to-I editing sites are located within mobile elements in non-coding parts of the genome. Editing of these non-coding sites is thought to have a critical role in protecting against activation of innate immunity by self-transcripts. Both recoding and non-coding events have implications for genome evolution and, when deregulated, may lead to disease. Finally, ADARs are now being adapted for RNA engineering purposes.}, } @article {pmid29692413, year = {2018}, author = {Spielmann, M and Lupiáñez, DG and Mundlos, S}, title = {Structural variation in the 3D genome.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {7}, pages = {453-467}, doi = {10.1038/s41576-018-0007-0}, pmid = {29692413}, issn = {1471-0064}, abstract = {Structural and quantitative chromosomal rearrangements, collectively referred to as structural variation (SV), contribute to a large extent to the genetic diversity of the human genome and thus are of high relevance for cancer genetics, rare diseases and evolutionary genetics. Recent studies have shown that SVs can not only affect gene dosage but also modulate basic mechanisms of gene regulation. SVs can alter the copy number of regulatory elements or modify the 3D genome by disrupting higher-order chromatin organization such as topologically associating domains. As a result of these position effects, SVs can influence the expression of genes distant from the SV breakpoints, thereby causing disease. The impact of SVs on the 3D genome and on gene expression regulation has to be considered when interpreting the pathogenic potential of these variant types.}, } @article {pmid29691606, year = {2018}, author = {Aj Harris, and Goldman, AD}, title = {Phylogenetic Reconstruction Shows Independent Evolutionary Origins of Mitochondrial Transcription Factors from an Ancient Family of RNA Methyltransferase Proteins.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {277-282}, pmid = {29691606}, issn = {1432-1432}, support = {16-IDEAS16-0001//National Aeronautics and Space Administration (US)/ ; MRI1427949//National Science Foundation/ ; }, abstract = {Here, we generate a robust phylogenetic framework for the rRNA adenine N(6)-methyltransferase (RAMTase) protein family that shows a more ancient and complex evolutionary history within the family than previously reported. RAMTases occur universally by descent across the three domains of life, and typical orthologs within the family perform methylation of the small subunits of ribosomal RNA (rRNA). However, within the RAMTase family, two different groups of mitochondrial transcription factors, mtTFB1 and mtTFB2, have evolved in eukaryotes through neofunctionalization. Previous phylogenetic analyses have suggested that mtTFB1 and mtTFB2 comprise sister clades that arose via gene duplication, which occurred sometime following the endosymbiosis event that produced the mitochondrion. Through dense and taxonomically broad sampling of RAMTase family members especially within bacteria, we found that these eukaryotic mitochondrial transcription factors, mtTFB1 and mtTFB2, have independent origins in phylogenetically distant clades such that their divergence most likely predates the last universal common ancestor of life. The clade of mtTFB2s comprises orthologs in Opisthokonts and the clade of mtTFB1s includes orthologs in Amoebozoa and Metazoa. Thus, we clearly demonstrate that the neofunctionalization producing the transcription factor function evolved twice independently within the RAMTase family. These results are consistent with and help to elucidate outcomes from prior experimental studies, which found that some members of mtTFB1 still perform the ancestral rRNA methylation function, and the results have broader implications for understanding the evolution of new protein functions. Our phylogenetic reconstruction is also in agreement with prior studies showing two independent origins of plastid RAMTases in Viridiplantae and other photosynthetic autotrophs. We believe that this updated phylogeny of RAMTases should provide a robust evolutionary framework for ongoing studies to identify and characterize the functions of these proteins within diverse organisms.}, } @article {pmid29691518, year = {2018}, author = {Vesper, I}, title = {Rent increase hits Europe's drug regulator before Brexit move.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {418}, doi = {10.1038/d41586-018-04917-4}, pmid = {29691518}, issn = {1476-4687}, mesh = {*Budgets ; Clinical Trials as Topic/economics/legislation & jurisprudence ; Drug Approval/economics/legislation & jurisprudence ; European Union/economics/*organization & administration ; Government Agencies/*economics/*organization & administration ; Humans ; Netherlands ; Patient Safety/legislation & jurisprudence ; Uncertainty ; United Kingdom ; }, } @article {pmid29691517, year = {2018}, author = {Abbott, A}, title = {Is 'friendly fire' in the brain provoking Alzheimer's disease?.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {426-428}, doi = {10.1038/d41586-018-04930-7}, pmid = {29691517}, issn = {1476-4687}, mesh = {Alzheimer Disease/complications/genetics/*immunology/therapy ; Amyotrophic Lateral Sclerosis/immunology ; Animals ; Anti-Inflammatory Agents/therapeutic use ; Brain/*immunology/pathology ; Clinical Trials as Topic ; Disease Models, Animal ; Disease Progression ; Humans ; Inflammasomes/metabolism ; Inflammation/*complications/*immunology/pathology/therapy ; Membrane Glycoproteins/genetics/metabolism ; Mice ; Microglia/*immunology/pathology ; NLR Family, Pyrin Domain-Containing 3 Protein/deficiency/genetics ; Parkinson Disease/immunology ; Receptors, Immunologic/genetics/metabolism ; Uncertainty ; }, } @article {pmid29691516, year = {2018}, author = {Popkin, G}, title = {US government considers charging for popular Earth-observing data.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {417-418}, doi = {10.1038/d41586-018-04874-y}, pmid = {29691516}, issn = {1476-4687}, mesh = {Costs and Cost Analysis ; Data Collection/*economics ; Datasets as Topic/economics/statistics & numerical data ; *Earth (Planet) ; Environmental Monitoring/*economics ; *Federal Government ; Remote Sensing Technology/*economics ; Research/*economics ; Research Personnel/economics ; Satellite Imagery/*economics/statistics & numerical data ; United States ; United States Department of Agriculture ; }, } @article {pmid29691515, year = {2018}, author = {Gaind, N}, title = {Mars probe poised to solve red planet's methane mystery.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {419}, doi = {10.1038/d41586-018-04948-x}, pmid = {29691515}, issn = {1476-4687}, mesh = {Carbon Dioxide/analysis ; Europe ; Exobiology/instrumentation/methods ; Extraterrestrial Environment/*chemistry ; *Mars ; Methane/*analysis ; Russia ; }, } @article {pmid29691514, year = {2018}, author = {Else, H}, title = {Scientists' early grant success fuels further funding.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {416-417}, doi = {10.1038/d41586-018-04958-9}, pmid = {29691514}, issn = {1476-4687}, } @article {pmid29691512, year = {2018}, author = {}, title = {Why a sweaty workout dampens appetite.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {411}, doi = {10.1038/d41586-018-04959-8}, pmid = {29691512}, issn = {1476-4687}, } @article {pmid29691509, year = {2018}, author = {Farahany, NA and Greely, HT and Hyman, S and Koch, C and Grady, C and Pașca, SP and Sestan, N and Arlotta, P and Bernat, JL and Ting, J and Lunshof, JE and Iyer, EPR and Hyun, I and Capestany, BH and Church, GM and Huang, H and Song, H}, title = {The ethics of experimenting with human brain tissue.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {429-432}, pmid = {29691509}, issn = {1476-4687}, support = {Z99 CL999999/CL/CLC NIH HHS/United States ; }, mesh = {Animals ; Brain/cytology/*physiology ; Chimera ; Consciousness/*physiology ; Death ; Embryo, Mammalian/cytology ; Heterografts ; Human Experimentation/*ethics ; Humans ; In Vitro Techniques ; Informed Consent/ethics ; Mice ; *Models, Biological ; Neurosciences/*ethics ; Organoids/cytology/growth & development/*physiology ; Ownership/ethics ; Rats ; Swine ; }, } @article {pmid29691508, year = {2018}, author = {Armour, A}, title = {Entangled vibrations in mechanical oscillators.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {444-445}, doi = {10.1038/d41586-018-04827-5}, pmid = {29691508}, issn = {1476-4687}, mesh = {*Vibration ; }, } @article {pmid29691506, year = {2018}, author = {Morack, T and Gilmour, R}, title = {Classic reaction re-engineered through molecular face recognition.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {438-439}, doi = {10.1038/d41586-018-04684-2}, pmid = {29691506}, issn = {1476-4687}, mesh = {*Face ; *Facial Recognition ; Pattern Recognition, Visual ; Recognition (Psychology) ; }, } @article {pmid29691505, year = {2018}, author = {Callaway, E}, title = {Flu virus finally sequenced in its native form.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {420}, doi = {10.1038/d41586-018-04908-5}, pmid = {29691505}, issn = {1476-4687}, mesh = {Base Sequence ; Genome, Viral/genetics ; Influenza A virus/*genetics ; RNA, Viral/*genetics ; Sequence Analysis, RNA/*trends ; }, } @article {pmid29691504, year = {2018}, author = {Schiermeier, Q}, title = {Clear signs of global warming will hit poorer countries first.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {415-416}, doi = {10.1038/d41586-018-04854-2}, pmid = {29691504}, issn = {1476-4687}, mesh = {Animals ; Developed Countries/economics/statistics & numerical data ; Developing Countries/*economics/*statistics & numerical data ; *Geographic Mapping ; Global Warming/*economics/*statistics & numerical data ; International Cooperation ; Models, Theoretical ; Rain ; Temperature ; Time Factors ; }, } @article {pmid29691503, year = {2018}, author = {}, title = {A nanomaterial to make your phone battery last.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {410}, doi = {10.1038/d41586-018-04884-w}, pmid = {29691503}, issn = {1476-4687}, } @article {pmid29691502, year = {2018}, author = {}, title = {Newfound chameleon species flashes rainbow colours and a nose like Pinocchio's.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {410}, doi = {10.1038/d41586-018-04883-x}, pmid = {29691502}, issn = {1476-4687}, } @article {pmid29691501, year = {2018}, author = {}, title = {A robot that builds IKEA furniture in a snap.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {411}, doi = {10.1038/d41586-018-04779-w}, pmid = {29691501}, issn = {1476-4687}, } @article {pmid29691500, year = {2018}, author = {}, title = {Sex pays off for stick insects despite costs.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {410-411}, doi = {10.1038/d41586-018-04778-x}, pmid = {29691500}, issn = {1476-4687}, } @article {pmid29691499, year = {2018}, author = {}, title = {Six-year-olds can cooperate to protect common assets.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {411}, doi = {10.1038/d41586-018-04744-7}, pmid = {29691499}, issn = {1476-4687}, } @article {pmid29691498, year = {2018}, author = {}, title = {Mass suicide documented in bacteria.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {410}, doi = {10.1038/d41586-018-04742-9}, pmid = {29691498}, issn = {1476-4687}, } @article {pmid29691497, year = {2018}, author = {}, title = {Booze-busting nanopills to help the liver.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {411}, doi = {10.1038/d41586-018-04732-x}, pmid = {29691497}, issn = {1476-4687}, } @article {pmid29691496, year = {2018}, author = {}, title = {Lost planet gave birth to space rock's diamonds.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {411}, doi = {10.1038/d41586-018-04728-7}, pmid = {29691496}, issn = {1476-4687}, } @article {pmid29691482, year = {2018}, author = {Johnson, KV and Foster, KR}, title = {Why does the microbiome affect behaviour?.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {10}, pages = {647-655}, doi = {10.1038/s41579-018-0014-3}, pmid = {29691482}, issn = {1740-1534}, abstract = {Growing evidence indicates that the mammalian microbiome can affect behaviour, and several symbionts even produce neurotransmitters. One common explanation for these observations is that symbionts have evolved to manipulate host behaviour for their benefit. Here, we evaluate the manipulation hypothesis by applying evolutionary theory to recent work on the gut-brain axis. Although the theory predicts manipulation by symbionts under certain conditions, these appear rarely satisfied by the genetically diverse communities of the mammalian microbiome. Specifically, any symbiont investing its resources to manipulate host behaviour is expected to be outcompeted within the microbiome by strains that do not manipulate and redirect their resources into growth and survival. Moreover, current data provide no clear evidence for manipulation. Instead, we show how behavioural effects can readily arise as a by-product of natural selection on microorganisms to grow within the host and natural selection on hosts to depend upon their symbionts. We argue that understanding why the microbiome influences behaviour requires a focus on microbial ecology and local effects within the host.}, } @article {pmid29691481, year = {2018}, author = {Ehrt, S and Schnappinger, D and Rhee, KY}, title = {Metabolic principles of persistence and pathogenicity in Mycobacterium tuberculosis.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {8}, pages = {496-507}, pmid = {29691481}, issn = {1740-1534}, support = {R01 AI063446/AI/NIAID NIH HHS/United States ; U19 AI111143/AI/NIAID NIH HHS/United States ; }, abstract = {Metabolism was once relegated to the supply of energy and biosynthetic precursors, but it has now become clear that it is a specific mediator of nearly all physiological processes. In the context of microbial pathogenesis, metabolism has expanded outside its canonical role in bacterial replication. Among human pathogens, this expansion has emerged perhaps nowhere more visibly than for Mycobacterium tuberculosis, the causative agent of tuberculosis. Unlike most pathogens, M. tuberculosis has evolved within humans, which are both host and reservoir. This makes unrestrained replication and perpetual quiescence equally incompatible strategies for survival as a species. In this Review, we summarize recent work that illustrates the diversity of metabolic functions that not only enable M. tuberculosis to establish and maintain a state of chronic infection within the host but also facilitate its survival in the face of drug pressure and, ultimately, completion of its life cycle.}, } @article {pmid29691326, year = {2018}, author = {Vaidyanathan, G}, title = {Core Concept: Microgrids offer flexible energy generation, for a price.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4298-4300}, doi = {10.1073/pnas.1804507115}, pmid = {29691326}, issn = {1091-6490}, } @article {pmid29691325, year = {2018}, author = {Kaneko, T and Bai, J and Akimoto, T and Francisco, JS and Yasuoka, K and Zeng, XC}, title = {Phase behaviors of deeply supercooled bilayer water unseen in bulk water.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4839-4844}, pmid = {29691325}, issn = {1091-6490}, abstract = {Akin to bulk water, water confined to an isolated nanoslit can show a wealth of new 2D phases of ice and amorphous ice, as well as unusual phase behavior. Indeed, 2D water phases, such as bilayer hexagonal ice and monolayer square ice, have been detected in the laboratory, confirming earlier computational predictions. Herein, we report theoretical evidence of a hitherto unreported state, namely, bilayer very low density amorphous ice (BL-VLDA), as well as evidence of a strong first-order transition between BL-VLDA and the BL amorphous ice (BL-A), and a weak first-order transition between BL-VLDA and the BL very low density liquid (BL-VLDL) water. The diffusivity of BL-VLDA is typically in the range of 10-9 cm2/s to 10-10 cm2/s. Similar to bulk (3D) water, 2D water can exhibit two forms of liquid in the deeply supercooled state. However, unlike supercooled bulk water, for which the two forms of liquid can coexist and merge into one at a critical point, the 2D BL-VLDL and BL high-density liquid (BL-HDL) phases are separated by the highly stable solid phase of BL-A whose melting line exhibits the isochore end point (IEP) near 220 K in the temperature-pressure diagram. Above the IEP temperature, BL-VLDL and BL-HDL are indistinguishable. At negative pressures, the metastable BL-VLDL exhibits a spatially and temporally heterogeneous structure induced by dynamic changes in the nanodomains, a feature much less pronounced in the BL-HDL.}, } @article {pmid29691324, year = {2018}, author = {Wang, ECY and Pjechova, M and Nightingale, K and Vlahava, VM and Patel, M and Ruckova, E and Forbes, SK and Nobre, L and Antrobus, R and Roberts, D and Fielding, CA and Seirafian, S and Davies, J and Murrell, I and Lau, B and Wilkie, GS and Suárez, NM and Stanton, RJ and Vojtesek, B and Davison, A and Lehner, PJ and Weekes, MP and Wilkinson, GWG and Tomasec, P}, title = {Suppression of costimulation by human cytomegalovirus promotes evasion of cellular immune defenses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4998-5003}, pmid = {29691324}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; G1000236//Medical Research Council/United Kingdom ; MR/P001602/1//Medical Research Council/United Kingdom ; WT090323MA//Wellcome Trust/United Kingdom ; MR/L008734/1//Medical Research Council/United Kingdom ; MC_UU_12014/3//Medical Research Council/United Kingdom ; 108070//Wellcome Trust/United Kingdom ; 101835//Wellcome Trust/United Kingdom ; }, mesh = {CD8-Positive T-Lymphocytes/*immunology/pathology ; Cell Line, Transformed ; Cytomegalovirus/genetics/*immunology ; Cytomegalovirus Infections/genetics/*immunology/pathology ; Humans ; *Immune Evasion ; *Immunity, Cellular ; Killer Cells, Natural/*immunology/pathology ; Viral Fusion Proteins/genetics/*immunology ; }, abstract = {CD58 is an adhesion molecule that is known to play a critical role in costimulation of effector cells and is intrinsic to immune synapse structure. Herein, we describe a virally encoded gene that inhibits CD58 surface expression. Human cytomegalovirus (HCMV) UL148 was necessary and sufficient to promote intracellular retention of CD58 during HCMV infection. Blocking studies with antagonistic anti-CD58 mAb and an HCMV UL148 deletion mutant (HCMV∆UL148) with restored CD58 expression demonstrated that the CD2/CD58 axis was essential for the recognition of HCMV-infected targets by CD8+ HCMV-specific cytotoxic T lymphocytes (CTLs). Further, challenge of peripheral blood mononuclear cells ex vivo with HCMV∆UL148 increased both CTL and natural killer (NK) cell degranulation against HCMV-infected cells, including NK-driven antibody-dependent cellular cytotoxicity, showing that UL148 is a modulator of the function of multiple effector cell subsets. Our data stress the effect of HCMV immune evasion functions on shaping the immune response, highlighting the capacity for their potential use in modulating immunity during the development of anti-HCMV vaccines and HCMV-based vaccine vectors.}, } @article {pmid29691323, year = {2018}, author = {Mallet, J}, title = {Invasive insect hybridizes with local pests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4819-4821}, pmid = {29691323}, issn = {1091-6490}, mesh = {Animals ; *Insect Control ; *Insecta ; }, } @article {pmid29691322, year = {2018}, author = {Price, DH}, title = {Transient pausing by RNA polymerase II.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4810-4812}, pmid = {29691322}, issn = {1091-6490}, support = {R01 GM035500/GM/NIGMS NIH HHS/United States ; R01 GM113935/GM/NIGMS NIH HHS/United States ; R21 AI130453/AI/NIAID NIH HHS/United States ; R35 GM126908/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA-Directed RNA Polymerases ; Promoter Regions, Genetic ; RNA Polymerase II/*genetics ; *Transcription, Genetic ; }, } @article {pmid29691321, year = {2018}, author = {Jain, V and Renne, R}, title = {Visualization of molecular biology: The LANA tether.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4816-4818}, pmid = {29691321}, issn = {1091-6490}, support = {P01 CA214091/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, Viral ; *Herpesvirus 8, Human ; *Virus Latency ; }, } @article {pmid29691320, year = {2018}, author = {Hammer, JA}, title = {Myosin goes for blood.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4813-4815}, pmid = {29691320}, issn = {1091-6490}, mesh = {*Blood Platelets ; *Myosins ; }, } @article {pmid29691319, year = {2018}, author = {Indra, I and Choi, J and Chen, CS and Troyanovsky, RB and Shapiro, L and Honig, B and Troyanovsky, SM}, title = {Spatial and temporal organization of cadherin in punctate adherens junctions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4406-E4415}, pmid = {29691319}, issn = {1091-6490}, support = {R01 AR044016/AR/NIAMS NIH HHS/United States ; R01 AR057992/AR/NIAMS NIH HHS/United States ; R01 GM062270/GM/NIGMS NIH HHS/United States ; R56 AR044016/AR/NIAMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Actins/genetics/*metabolism ; Adherens Junctions/genetics/*metabolism ; Cadherins/genetics/*metabolism ; Cell Line ; Humans ; *Molecular Imaging ; }, abstract = {Adherens junctions (AJs) play a fundamental role in tissue integrity; however, the organization and dynamics of the key AJ transmembrane protein, E-cadherin, both inside and outside of AJs, remain controversial. Here we have studied the distribution and motility of E-cadherin in punctate AJs (pAJs) of A431 cells. Using single-molecule localization microscopy, we show that pAJs in these cells reach more than 1 μm in length and consist of several cadherin clusters with crystal-like density interspersed within sparser cadherin regions. Notably, extrajunctional cadherin appears to be monomeric, and its density is almost four orders of magnitude less than observed in the pAJ regions. Two alternative strategies of tracking cadherin motion within individual junctions show that pAJs undergo actin-dependent rapid-on the order of seconds-internal reorganizations, during which dense clusters disassemble and their cadherins are immediately reused for new clusters. Our results thus modify the classical view of AJs by depicting them as mosaics of cadherin clusters, the short lifetimes of which enable stable overall morphology combined with rapid internal rearrangements.}, } @article {pmid29691318, year = {2018}, author = {Woo, J and Min, JO and Kang, DS and Kim, YS and Jung, GH and Park, HJ and Kim, S and An, H and Kwon, J and Kim, J and Shim, I and Kim, HG and Lee, CJ and Yoon, BE}, title = {Control of motor coordination by astrocytic tonic GABA release through modulation of excitation/inhibition balance in cerebellum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {5004-5009}, pmid = {29691318}, issn = {1091-6490}, mesh = {Animals ; Astrocytes/cytology/*metabolism ; Bestrophins/genetics/metabolism ; Cerebellum/cytology/*metabolism ; Mice, Inbred BALB C ; Mice, Knockout ; Monoamine Oxidase/genetics/metabolism ; Psychomotor Performance/*physiology ; Purkinje Cells/cytology/*metabolism ; Synaptic Transmission/*physiology ; gamma-Aminobutyric Acid/genetics/*metabolism ; }, abstract = {Tonic inhibition in the brain is mediated through an activation of extrasynaptic GABAA receptors by the tonically released GABA, resulting in a persistent GABAergic inhibitory action. It is one of the key regulators for neuronal excitability, exerting a powerful action on excitation/inhibition balance. We have previously reported that astrocytic GABA, synthesized by monoamine oxidase B (MAOB), mediates tonic inhibition via GABA-permeable bestrophin 1 (Best1) channel in the cerebellum. However, the role of astrocytic GABA in regulating neuronal excitability, synaptic transmission, and cerebellar brain function has remained elusive. Here, we report that a reduction of tonic GABA release by genetic removal or pharmacological inhibition of Best1 or MAOB caused an enhanced neuronal excitability in cerebellar granule cells (GCs), synaptic transmission at the parallel fiber-Purkinje cell (PF-PC) synapses, and motor performance on the rotarod test, whereas an augmentation of tonic GABA release by astrocyte-specific overexpression of MAOB resulted in a reduced neuronal excitability, synaptic transmission, and motor performance. The bidirectional modulation of astrocytic GABA by genetic alteration of Best1 or MAOB was confirmed by immunostaining and in vivo microdialysis. These findings indicate that astrocytes are the key player in motor coordination through tonic GABA release by modulating neuronal excitability and could be a good therapeutic target for various movement and psychiatric disorders, which show a disturbed excitation/inhibition balance.}, } @article {pmid29690935, year = {2018}, author = {Ueki, A and Okuma, T and Hamamoto, S and Kageyama, K and Murai, K and Miki, Y}, title = {Combination therapy involving radiofrequency ablation and targeted chemotherapy with bevacizumab plus paclitaxel and cisplatin in a rabbit VX2 lung tumor model.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {251}, pmid = {29690935}, issn = {1756-0500}, support = {25461887//Japan Society for the Promotion of Science/ ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Bevacizumab/*pharmacology ; Carcinoma/*drug therapy/*surgery ; Catheter Ablation/*methods ; Cell Line, Tumor ; Cisplatin/*pharmacology ; Combined Modality Therapy ; Disease Models, Animal ; Drug Therapy, Combination ; Female ; Lung Neoplasms/*drug therapy/*surgery ; Paclitaxel/*pharmacology ; Rabbits ; }, abstract = {OBJECTIVE: Radiofrequency ablation (RFA) is less effective for large tumors > 3 cm in diameter. Various studies of combination therapy using RFA and other treatments have been conducted to improve the results of RFA treatment of lung tumors, survival was extended in a tumor model when RFA was followed by concomitant use of systemic chemotherapy. Bevacizumab (BCM) is a one of molecular target drugs. Numerous clinical trials and reports have shown BCM's effect when used in combination with cisplatin (CDDP) in lung tumor. Our objective is to evaluate the survival of concurrent, combined use of radiofrequency ablation and BCM, and platinum-doublet chemotherapy [CDDP/paclitaxel (PTX)] in a rabbit VX2 lung tumor.

RESULTS: Survival times of the RFA alone, CDDP/PTX, CDDP/PTX/BCM, RFA/CDDP/PTX, and RFA/CDDP/PTX/BCM groups were significantly prolonged compared to that of the control group (P = 0.0055, P = 0.0055, P = 0.0004, P = 0.0002, P = 0.0019, respectively). Survival of the RFA/CDDP/PTX/BCM group was not significantly prolonged compared to the RFA alone (P = 0.53) and CDDP/PTX/BCM group (P = 0.68), while showing a significantly shorter survival time than that of the RFA/CDDP/PTX group (P = 0.017). The addition to BCM with combination RFA and systemic therapy with CDDP/PTX did not have a positive effect on survival.}, } @article {pmid29690931, year = {2018}, author = {De Rudder, C and Calatayud Arroyo, M and Lebeer, S and Van de Wiele, T}, title = {Modelling upper respiratory tract diseases: getting grips on host-microbe interactions in chronic rhinosinusitis using in vitro technologies.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {75}, pmid = {29690931}, issn = {2049-2618}, support = {118499 / 12R2717N LV//Fonds Wetenschappelijk Onderzoek/International ; 150052//Agentschap voor Innovatie door Wetenschap en Technologie/International ; 150052//Agentschap voor Innovatie door Wetenschap en Technologie/International ; }, mesh = {Cellular Microenvironment ; Chronic Disease ; *Host-Pathogen Interactions ; Humans ; *Microbiota ; *Models, Biological ; Respiratory Mucosa/immunology/metabolism ; Respiratory Tract Diseases/*etiology/*pathology ; Rhinitis/etiology/pathology ; Sinusitis/etiology/pathology ; }, abstract = {Chronic rhinosinusitis (CRS) is a chronic inflammation of the mucosa of the nose and paranasal sinuses affecting approximately 11% of the adult population in Europe. Inadequate immune responses, as well as a dysbiosis of the sinonasal microbiota, have been put forward as aetiological factors of the disease. However, despite the prevalence of this disease, there is no consensus on the aetiology and mechanisms of pathogenesis of CRS. Further research requires in vitro models mimicking the healthy and diseased host environment along with the sinonasal microbiota. This review aims to provide an overview of CRS model systems and proposes in vitro modelling strategies to conduct mechanistic research in an ecological framework on the sinonasal microbiota and its interactions with the host in health and CRS.}, } @article {pmid29690929, year = {2018}, author = {Owusu, M and Marfo, KS and Acheampong, G and Arthur, A and Sarpong, N and Im, J and Mogeni, OD and Annan, A and Chiang, HY and Kuo, CH and Park, SE and Marks, F and Owusu-Dabo, E and Adu-Sarkodie, Y}, title = {Gonococcal sepsis in a 32-year-old female: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {253}, pmid = {29690929}, issn = {1756-0500}, mesh = {Adult ; Bacteremia/blood/diagnosis/drug therapy/*etiology ; Female ; Ghana ; Gonorrhea/blood/*complications/diagnosis/drug therapy ; Humans ; Neisseria gonorrhoeae/drug effects/isolation & purification/*pathogenicity ; }, abstract = {BACKGROUND: Neisseria gonorrhoeae is a Gram-negative bacterium which affects the urethra, throat, rectum and cervix of patients and often associated with sexually transmitted infections. The global epidemiology of the disease is not well characterised especially in resource constraint countries due to poor diagnostic capacity and inefficient reporting systems. Although important, little is known about the propensity of this bacterium to cause sepsis in immunocompetent individuals.

CASE PRESENTATION: A 32-year-old female presented with fever and generalised malaise to a rural hospital in Ghana. The patient had previously been diagnosed as having enteric fever from a neighbouring health facility. Blood and urine samples were collected from the patient and cultured using standard microbiological and molecular techniques. Neisseria gonorrhoeae was isolated from the blood which was resistant to penicillin, ciprofloxacin and cotrimoxazole. The patient recovered following ceftriaxone and azithromycin treatment.

CONCLUSION: This case highlights the importance of N. gonorrhoeae in causing sepsis and emphasises the need for blood culture investigation in diagnosis of patients presenting with fever.}, } @article {pmid29690923, year = {2018}, author = {Hartman, K and van der Heijden, MGA and Wittwer, RA and Banerjee, S and Walser, JC and Schlaeppi, K}, title = {Correction to: Cropping practices manipulate abundance patterns of root and soil microbiome members paving the way to smart farming.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {74}, pmid = {29690923}, issn = {2049-2618}, abstract = {Following publication of the original article [1], the authors reported that while the ordination graphs are all correct, the symbols in the legend are wrong.}, } @article {pmid29690922, year = {2018}, author = {Jaenicke, S and Albaum, SP and Blumenkamp, P and Linke, B and Stoye, J and Goesmann, A}, title = {Flexible metagenome analysis using the MGX framework.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {76}, pmid = {29690922}, issn = {2049-2618}, mesh = {*Database Management Systems ; *Metagenome ; Metagenomics/*methods ; Microbiota ; Reproducibility of Results ; User-Computer Interface ; Workflow ; }, abstract = {BACKGROUND: The characterization of microbial communities based on sequencing and analysis of their genetic information has become a popular approach also referred to as metagenomics; in particular, the recent advances in sequencing technologies have enabled researchers to study even the most complex communities. Metagenome analysis, the assignment of sequences to taxonomic and functional entities, however, remains a tedious task: large amounts of data need to be processed. There are a number of approaches addressing particular aspects, but scientific questions are often too specific to be answered by a general-purpose method.

RESULTS: We present MGX, a flexible and extensible client/server-framework for the management and analysis of metagenomic datasets; MGX features a comprehensive set of adaptable workflows required for taxonomic and functional metagenome analysis, combined with an intuitive and easy-to-use graphical user interface offering customizable result visualizations. At the same time, MGX allows to include own data sources and devise custom analysis pipelines, thus enabling researchers to perform basic as well as highly specific analyses within a single application.

CONCLUSIONS: With MGX, we provide a novel metagenome analysis platform giving researchers access to the most recent analysis tools. MGX covers taxonomic and functional metagenome analysis, statistical evaluation, and a wide range of visualizations easing data interpretation. Its default taxonomic classification pipeline provides equivalent or superior results in comparison to existing tools.}, } @article {pmid29690918, year = {2018}, author = {O'Hara, L and O'Shaughnessy, PJ and Freeman, TC and Smith, LB}, title = {Modelling steroidogenesis: a framework model to support hypothesis generation and testing across endocrine studies.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {252}, pmid = {29690918}, issn = {1756-0500}, support = {BB/J015105/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N007026/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/N002970/1//Medical Research Council/United Kingdom ; }, mesh = {Gonadal Steroid Hormones/*biosynthesis ; Humans ; *Models, Biological ; Steroids/*biosynthesis ; }, abstract = {OBJECTIVE: Steroid hormones are responsible for the control of a wide range of physiological processes such as development, growth, reproduction, metabolism, and aging. Because of the variety of enzymes, substrates and products that take part in steroidogenesis and the compartmentalisation of its constituent reactions, it is a complex process to visualise and document. One of the goals of systems biology is to quantitatively describe the behaviour of complex biological systems that involve the interaction of many components. This can be done by representing these interactions visually in a pathway model and then optionally constructing a mathematical model of the interactions.

RESULTS: We have used the modified Edinburgh Pathway Notation to construct a framework diagram describing human steroidogenic pathways, which will be of use to endocrinologists. To demonstrate further utility, we show how such models can be parameterised with empirical data within the software Graphia Professional, to recapitulate specific examples of steroid hormone production, and also to mimic gene knockout. These framework models support in silico hypothesis generation and testing with utility across endocrine endpoints, with significant potential to reduce costs, time and animal numbers, whilst informing the design of planned studies.}, } @article {pmid29690879, year = {2018}, author = {Inglin, RC and Meile, L and Stevens, MJA}, title = {Clustering of Pan- and Core-genome of Lactobacillus provides Novel Evolutionary Insights for Differentiation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {284}, pmid = {29690879}, issn = {1471-2164}, support = {145214//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; }, mesh = {Algorithms ; Cluster Analysis ; *Evolution, Molecular ; Gene Transfer, Horizontal ; *Genome, Bacterial ; Genomics ; Lactobacillus/*genetics ; }, abstract = {BACKGROUND: Bacterial taxonomy aims to classify bacteria based on true evolutionary events and relies on a polyphasic approach that includes phenotypic, genotypic and chemotaxonomic analyses. Until now, complete genomes are largely ignored in taxonomy. The genus Lactobacillus consists of 173 species and many genomes are available to study taxonomy and evolutionary events.

RESULTS: We analyzed and clustered 98 completely sequenced genomes of the genus Lactobacillus and 234 draft genomes of 5 different Lactobacillus species, i.e. L. reuteri, L. delbrueckii, L. plantarum, L. rhamnosus and L. helveticus. The core-genome of the genus Lactobacillus contains 266 genes and the pan-genome 20'800 genes. Clustering of the Lactobacillus pan- and core-genome resulted in two highly similar trees. This shows that evolutionary history is traceable in the core-genome and that clustering of the core-genome is sufficient to explore relationships. Clustering of core- and pan-genomes at species' level resulted in similar trees as well. Detailed analyses of the core-genomes showed that the functional class "genetic information processing" is conserved in the core-genome but that "signaling and cellular processes" is not. The latter class encodes functions that are involved in environmental interactions. Evolution of lactobacilli seems therefore directed by the environment. The type species L. delbrueckii was analyzed in detail and its pan-genome based tree contained two major clades whose members contained different genes yet identical functions. In addition, evidence for horizontal gene transfer between strains of L. delbrueckii, L. plantarum, and L. rhamnosus, and between species of the genus Lactobacillus is presented. Our data provide evidence for evolution of some lactobacilli according to a parapatric-like model for species differentiation.

CONCLUSIONS: Core-genome trees are useful to detect evolutionary relationships in lactobacilli and might be useful in taxonomic analyses. Lactobacillus' evolution is directed by the environment and HGT.}, } @article {pmid29690872, year = {2018}, author = {Lal, P and Tanabe, H and Suster, ML and Ailani, D and Kotani, Y and Muto, A and Itoh, M and Iwasaki, M and Wada, H and Yaksi, E and Kawakami, K}, title = {Identification of a neuronal population in the telencephalon essential for fear conditioning in zebrafish.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {45}, pmid = {29690872}, issn = {1741-7007}, abstract = {BACKGROUND: Fear conditioning is a form of learning essential for animal survival and used as a behavioral paradigm to study the mechanisms of learning and memory. In mammals, the amygdala plays a crucial role in fear conditioning. In teleost, the medial zone of the dorsal telencephalon (Dm) has been postulated to be a homolog of the mammalian amygdala by anatomical and ablation studies, showing a role in conditioned avoidance response. However, the neuronal populations required for a conditioned avoidance response via the Dm have not been functionally or genetically defined.

RESULTS: We aimed to identify the neuronal population essential for fear conditioning through a genetic approach in zebrafish. First, we performed large-scale gene trap and enhancer trap screens, and created transgenic fish lines that expressed Gal4FF, an engineered version of the Gal4 transcription activator, in specific regions in the brain. We then crossed these Gal4FF-expressing fish with the effector line carrying the botulinum neurotoxin gene downstream of the Gal4 binding sequence UAS, and analyzed the double transgenic fish for active avoidance fear conditioning. We identified 16 transgenic lines with Gal4FF expression in various brain areas showing reduced performance in avoidance responses. Two of them had Gal4 expression in populations of neurons located in subregions of the Dm, which we named 120A-Dm neurons. Inhibition of the 120A-Dm neurons also caused reduced performance in Pavlovian fear conditioning. The 120A-Dm neurons were mostly glutamatergic and had projections to other brain regions, including the hypothalamus and ventral telencephalon.

CONCLUSIONS: Herein, we identified a subpopulation of neurons in the zebrafish Dm essential for fear conditioning. We propose that these are functional equivalents of neurons in the mammalian pallial amygdala, mediating the conditioned stimulus-unconditioned stimulus association. Thus, the study establishes a basis for understanding the evolutionary conservation and diversification of functional neural circuits mediating fear conditioning in vertebrates.}, } @article {pmid29690867, year = {2018}, author = {Yu, H and Waddell, JN and Kuang, S and Tellam, RL and Cockett, NE and Bidwell, CA}, title = {Identification of genes directly responding to DLK1 signaling in Callipyge sheep.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {283}, pmid = {29690867}, issn = {1471-2164}, mesh = {Animals ; Cells, Cultured ; Cyclic Nucleotide Phosphodiesterases, Type 4/genetics/metabolism ; Hypertrophy ; Membrane Proteins/*genetics/metabolism ; Muscle, Skeletal/metabolism/pathology ; Myoblasts/cytology/drug effects/metabolism ; Myosin Heavy Chains/genetics/metabolism ; Nuclear Proteins/genetics/metabolism ; Pregnancy Proteins/genetics/metabolism ; Recombinant Proteins/biosynthesis/isolation & purification/pharmacology ; Sheep/genetics ; Signal Transduction/genetics ; Transcriptome/drug effects ; Up-Regulation/drug effects ; }, abstract = {BACKGROUND: In food animal agriculture, there is a need to identify the mechanisms that can improve the efficiency of muscle growth and protein accretion. Callipyge sheep provide excellent machinery since the up-regulation of DLK1 and RTL1 results in extreme postnatal muscle hypertrophy in distinct muscles. The aim of this study is to distinguish the genes that directly respond to DLK1 and RTL1 signaling from the genes that change as the result of muscle specific effects.

RESULTS: The quantitative PCR results indicated that DLK1 expression was significantly increased in hypertrophied muscles but not in non-hypertrophied muscles. However, RTL1 was up-regulated in both hypertrophied and non-hypertrophied muscles. Five genes, including PARK7, DNTTIP1, SLC22A3, METTL21E and PDE4D, were consistently co-expressed with DLK1, and therefore were possible transcriptional target genes responding to DLK1 signaling. Treatment of myoblast and myotubes with DLK1 protein induced an average of 1.6-fold and 1.4-fold increase in Dnttip1 and Pde4d expression respectively. Myh4 expression was significantly elevated in DLK1-treated myotubes, whereas the expression of Mettl21e was significantly increased in the DLK1-treated myoblasts but reduced in DLK1-treated myotubes. DLK1 treatment had no impact on Park7 expression. In addition, Park7 and Dnttip1 increased Myh4 and decreased Myh7 promoter activity, resemble to the effects of Dlk1. In contrast, expression of Mettl21e increased Myh7 and decreased Myh4 luciferase activity.

CONCLUSION: The study provided additional supports that RTL1 alone was insufficient to induce muscle hypertrophy and concluded that DLK1 was likely the primary effector of the hypertrophy phenotype. The results also suggested that DNTTIP1 and PDE4D were secondary effector genes responding to DLK1 signaling resulting in muscle fiber switch and muscular hypertrophy in callipyge lamb.}, } @article {pmid29690866, year = {2018}, author = {Rajeh, A and Lv, J and Lin, Z}, title = {Heterogeneous rates of genome rearrangement contributed to the disparity of species richness in Ascomycota.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {282}, pmid = {29690866}, issn = {1471-2164}, mesh = {Ascomycota/*genetics ; DNA Transposable Elements/genetics ; Evolution, Molecular ; Gene Order ; Genome, Fungal/*genetics ; Phylogeny ; Segmental Duplications, Genomic/genetics ; }, abstract = {BACKGROUND: Chromosomal rearrangements have been shown to facilitate speciation through creating a barrier of gene flow. However, it is not known whether heterogeneous rates of chromosomal rearrangement at the genome scale contributed to the huge disparity of species richness among different groups of organisms, which is one of the most remarkable and pervasive patterns on Earth. The largest fungal phylum Ascomycota is an ideal study system to address this question because it comprises three subphyla (Saccharomycotina, Taphrinomycotina, and Pezizomycotina) whose species numbers differ by two orders of magnitude (59,000, 1000, and 150 respectively).

RESULTS: We quantified rates of genome rearrangement for 71 Ascomycota species that have well-assembled genomes. The rates of inter-species genome rearrangement, which were inferred based on the divergence rates of gene order, are positively correlated with species richness at both ranks of subphylum and class in Ascomycota. This finding is further supported by our quantification of intra-species rearrangement rates based on paired-end genome sequencing data of 216 strains from three representative species, suggesting a difference of intrinsic genome instability among Ascomycota lineages. Our data also show that different rates of imbalanced rearrangements, such as deletions, are a major contributor to the heterogenous rearrangement rates.

CONCLUSIONS: Various lines of evidence in this study support that a higher rate of rearrangement at the genome scale might have accelerated the speciation process and increased species richness during the evolution of Ascomycota species. Our findings provide a plausible explanation for the species disparity among Ascomycota lineages, which will be valuable to unravel the underlying causes for the huge disparity of species richness in various taxonomic groups.}, } @article {pmid29690862, year = {2018}, author = {Wang, Y and Guo, S and Wang, L and Wang, L and He, X and Shu, S and Sun, J and Lu, N}, title = {Identification of microRNAs associated with the exogenous spermidine-mediated improvement of high-temperature tolerance in cucumber seedlings (Cucumis sativus L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {285}, pmid = {29690862}, issn = {1471-2164}, support = {31471869//National Natural Science Foundation of China/ ; 31401919//National Natural Science Foundation of China/ ; 31272209//National Natural Science Foundation of China/ ; 2016YED0201007//National Key Research and Development Program of Chin/ ; CARS-25-C-03//China Agriculture Research System/ ; }, mesh = {Cucumis sativus/*genetics/growth & development ; Gene Expression Regulation/drug effects ; Gene Library ; High-Throughput Nucleotide Sequencing ; Hot Temperature ; MicroRNAs/genetics/*metabolism ; Seedlings/drug effects/genetics/growth & development ; Sequence Analysis, RNA ; Spermidine/*pharmacology ; Stress, Physiological/genetics ; Thermotolerance/*drug effects/genetics ; }, abstract = {BACKGROUND: High-temperature stress inhibited the growth of cucumber seedlings. Foliar spraying of 1.0 mmol·L- 1 exogenous spermidine (Spd) to the sensitive cucumber cultivar 'Jinchun No. 2' grown at high-temperature (42 °C/32 °C) in an artificial climate box improved the high-temperature tolerance. Although there have been many reports on the response of microRNAs (miRNAs) to high-temperature stress, the mechanism by which exogenous Spd may mitigate the damage of high-temperature stress through miRNA-mediated regulation has not been studied.

RESULTS: To elucidate the regulation of miRNAs in response to exogenous Spd-mediated improvement of high-temperature tolerance, four small RNA libraries were constructed from cucumber leaves and sequenced: untreated-control (CW), Spd-treated (CS), high-temperature stress (HW), and Spd-treated and high-temperature stress (HS). As a result, 107 known miRNAs and 79 novel miRNAs were identified. Eight common differentially expressed miRNAs (miR156d-3p, miR170-5p, miR2275-5p, miR394a, miR479b, miR5077, miR5222 and miR6475) were observed in CS/CW, HW/CW, HS/CW and HS/HW comparison pairs, which were the first set of miRNAs that responded to not only high-temperature stress but also exogenous Spd in cucumber seedlings. Five of the eight miRNAs were predicted to target 107 potential genes. Gene function and pathway analyses highlighted the integral role that these miRNAs and target genes probably play in the improvement of the high-temperature tolerance of cucumber seedlings through exogenous Spd application.

CONCLUSIONS: Our study identified the first set of miRNAs associated with the exogenous Spd-mediated improvement of high-temperature tolerance in cucumber seedlings. The results could help to promote further studies on the complex molecular mechanisms underlying high-temperature tolerance in cucumber and provide a theoretical basis for the high-quality and efficient cultivation of cucumber with high-temperature resistance.}, } @article {pmid29690861, year = {2018}, author = {English, AM and Waters, SM and Cormican, P and Byrne, CJ and Fair, S and Kenny, DA}, title = {Effect of early calf-hood nutrition on the transcriptomic profile of subcutaneous adipose tissue in Holstein-Friesian bulls.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {281}, pmid = {29690861}, issn = {1471-2164}, support = {GOIPG/2013/1391//Irish Research Council/ ; 11/S/116//Irish Department of Agriculture, Food and the Marine/ ; }, mesh = {Animals ; Cattle ; Cell Size ; Endocrine System/physiology ; Male ; *Nutritional Status ; Subcutaneous Fat/cytology/*metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Adipose tissue is a major endocrine organ and is thought to play a central role in the metabolic control of reproductive function in cattle. Plane of nutrition during early life has been shown to influence the timing of puberty in both male and female cattle, though the exact biological mechanisms involved are currently unknown. The aim of this study was to investigate the effect of early calf-hood nutrition on the transcriptomic profile of subcutaneous adipose tissue in Holstein-Friesian bulls to identify possible downstream effects on reproductive physiology.

RESULTS: Holstein-Friesian bull calves with a mean (±S.D.) age and bodyweight of 19 (±8.2) days and 47.5 (±5.3) kg, respectively, were assigned to either a high (n = 10) or low (n = 10) plane of nutrition. Calves were fed in order to achieve an overall growth rate of 1.08 and 0.57 kg/day for the high and low plane of nutrition treatments, respectively. At 126 days of age, the bulls were euthanized, subcutaneous adipose tissue samples were harvested and RNAseq analysis was performed. There were 674 genes differentially expressed in adipose tissue of calves on the low compared with the high plane of nutrition (P < 0.05; FDR < 0.05; fold change > 2.0). High plane of nutrition positively altered the expression of genes across an array of putative biological processes but the most dominant cellular processes affected were cellular energy production and branched chain amino acid degradation. A high plane of nutrition caused upregulation of genes such as leptin (LEP) and adiponectin (ADIPOQ), which are known to directly affect reproductive function.

CONCLUSIONS: These results provide an insight into the effect of augmenting the plane of nutrition of Holstein-Friesian bull calves in the prepubertal period on the transcriptome of adipose tissue.}, } @article {pmid29689409, year = {2018}, author = {Liu, J and Liu, H and Zhang, H}, title = {Phylogeny and evolutionary radiation of the marine mussels (Bivalvia: Mytilidae) based on mitochondrial and nuclear genes.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {233-240}, doi = {10.1016/j.ympev.2018.04.019}, pmid = {29689409}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Bayes Theorem ; *Biological Evolution ; Bivalvia/genetics ; Cell Nucleus/*genetics ; *Genes, Mitochondrial ; Genetic Variation ; Mytilidae/*classification/*genetics ; *Phylogeny ; RNA, Ribosomal, 28S/genetics ; Sequence Analysis, DNA ; Time Factors ; }, abstract = {The marine mussels (Mytilidae) are distributed in the oceans worldwide and occupy various habitats with diverse life styles. However, their taxonomy and phylogeny remain unclear from genus to family level due to equivocal morphological and anatomical characters among some taxa. In this study, we inferred the deep phylogenetic relationships among 42 mytiloid species, 19 genera, and five subfamilies of the extant marine mussels by using two mitochondrial (COI and 16S rRNA) and three nuclear (18S and 28S rRNA, and histone H3) genes. Phylogeny was reconstructed with a combination of five genes using Bayesian inference and maximum likelihood method, and divergence time was estimated for the major nodes using a relaxed clock model with three fossil calibrations. Phylogenetic trees revealed two major clades (Clades 1 and 2). In Clade 1, the deep-sea mussels (subfamily Bathymodiolinae) were sister to subfamily Modiolinae (represented by Modiolus), and then was clustered with Leiosolenus (subfamily Lithophaginae). Clade 2 comprised Lithophaga (Lithophaginae) and subfamily Mytilinae. Additionally, a Modiolus species and Musculus senhousia (subfamily Crenellinae) were positioned within the subfamily Mytilinae. The phylogenetic results strongly indicated monophyly of Mytilidae and Bathymodiolinae, polyphyly of Modiolinae and Lithophaginae, and paraphyly of Mytilinae. Divergence time estimation showed an ancient and gradual divergence in most mussel groups, whereas the deep-sea mussels originated recently and diverged rapidly during the Paleogene. The present study provides new insight into the evolutionary history of the marine mussels, and supports taxonomic revision for this important bivalve group.}, } @article {pmid29688851, year = {2018}, author = {Civáň, P and Brown, TA}, title = {Role of genetic introgression during the evolution of cultivated rice (Oryza sativa L.).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {57}, pmid = {29688851}, issn = {1471-2148}, support = {339941//European Research Council/International ; }, mesh = {*Agriculture ; Alleles ; *Biological Evolution ; Crops, Agricultural/*genetics ; Gene Flow ; Gene Frequency/genetics ; Genome, Plant ; Oryza/*genetics ; Phenotype ; Phylogeography ; Principal Component Analysis ; }, abstract = {BACKGROUND: Models for the origins of cultivated rice currently fall into two groups: ones that identify independent domestications of the indica, japonica and possibly also the aus types, and others that propose that the domestication phenotype was initially acquired by japonica, the underlying alleles then transferred by introgression to other pre-domesticated populations, giving the indica and aus varieties. Identifying the impact of past gene flow on cultivated rice genomes is therefore crucial to distinguishing between these models and understanding the domestication history of rice. To this end, we used population-scale polymorphism data to identify the progenitor gene pools of indica, japonica and aus. Variation shared among the cultivated groups but absent from at least one progenitor population was identified, and genomic blocks putatively transferred by gene flow among cultivated groups mapped.

RESULTS: Introgression signals were absent at the major domestication loci (Prog1, Rc, qSH1, qSH3, Sh4) of indica and aus, indicating that these loci were unaffected by gene flow from japonica. Other domestication-related loci (Ghd7, LABA1, Kala4, LG1) show signals of introgression from japonica or indica to aus. There is a strong signal for LABA1 in japonica, possibly indicating introgression from indica. The indica genome is the least affected by gene flow, with just a few short regions with allelic frequencies slightly altered by introgression from japonica.

CONCLUSION: Introgression has occurred during the evolution of cultivated rice, but was not responsible for transfer of the key domestication alleles between the cultivated groups. The results are therefore consistent with models in which japonica, indica and aus were domesticated independently, with each of these cultivated groups acquiring the domestication alleles from standing variation in wild rice, without a significant contribution from inter-group gene flow.}, } @article {pmid29688842, year = {2018}, author = {Artemov, GN and Bondarenko, SM and Naumenko, AN and Stegniy, VN and Sharakhova, MV and Sharakhov, IV}, title = {Partial-arm translocations in evolution of malaria mosquitoes revealed by high-coverage physical mapping of the Anopheles atroparvus genome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {278}, pmid = {29688842}, issn = {1471-2164}, support = {15-14-20011//Russian Science Foundation/ ; }, mesh = {Animals ; Anopheles/*genetics/physiology ; *Evolution, Molecular ; Female ; Genome, Insect/*genetics ; *Malaria ; Ovary/cytology ; *Physical Chromosome Mapping ; Synteny ; Translocation, Genetic/*genetics ; }, abstract = {BACKGROUND: Malaria mosquitoes have had a remarkable stability in the number of chromosomes in their karyotype (2n = 6) during 100 million years of evolution. Moreover, autosomal arms were assumed to maintain their integrity even if their associations with each other changed via whole-arm translocations. Here we use high-coverage comparative physical genome mapping of three Anopheles species to test the extent of evolutionary conservation of chromosomal arms in malaria mosquitoes.

RESULTS: In this study, we developed a physical genome map for Anopheles atroparvus, one of the dominant malaria vectors in Europe. Using fluorescence in situ hybridization (FISH) of DNA probes with the ovarian nurse cell polytene chromosomes and synteny comparison, we anchored 56 genomic scaffolds to the An. atroparvus chromosomes. The obtained physical map represents 89.6% of the An. atroparvus genome. This genome has the second highest mapping coverage among Anophelinae assemblies after An. albimanus, which has 98.2% of the genome assigned to its chromosomes. A comparison of the An. atroparvus, An. albimanus, and An. gambiae genomes identified partial-arm translocations between the autosomal arms that break down the integrity of chromosome elements in evolution affecting the structure of the genetic material in the pericentromeric regions. Unlike An. atroparvus and An. albimanus, all chromosome elements of An. gambiae are fully syntenic with chromosome elements of the putative ancestral Anopheles karyotype. We also detected nonrandom distribution of large conserved synteny blocks and confirmed a higher rate of inversion fixation in the X chromosome compared with autosomes.

CONCLUSIONS: Our study demonstrates the power of physical mapping for understanding the genome evolution in malaria mosquitoes. The results indicate that syntenic relationships among chromosome elements of Anopheles species have not been fully preserved because of multiple partial-arm translocations.}, } @article {pmid29688545, year = {2018}, author = {Caspermeyer, J}, title = {Using Whole-Genome Analysis to Home in on Racing Pigeon Performance.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1296}, doi = {10.1093/molbev/msy064}, pmid = {29688545}, issn = {1537-1719}, } @article {pmid29688544, year = {2018}, author = {Martin, HC and Batty, EM and Hussin, J and Westall, P and Daish, T and Kolomyjec, S and Piazza, P and Bowden, R and Hawkins, M and Grant, T and Moritz, C and Grutzner, F and Gongora, J and Donnelly, P}, title = {Insights into Platypus Population Structure and History from Whole-Genome Sequencing.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1238-1252}, pmid = {29688544}, issn = {1537-1719}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {The platypus is an egg-laying mammal which, alongside the echidna, occupies a unique place in the mammalian phylogenetic tree. Despite widespread interest in its unusual biology, little is known about its population structure or recent evolutionary history. To provide new insights into the dispersal and demographic history of this iconic species, we sequenced the genomes of 57 platypuses from across the whole species range in eastern mainland Australia and Tasmania. Using a highly improved reference genome, we called over 6.7 M SNPs, providing an informative genetic data set for population analyses. Our results show very strong population structure in the platypus, with our sampling locations corresponding to discrete groupings between which there is no evidence for recent gene flow. Genome-wide data allowed us to establish that 28 of the 57 sampled individuals had at least a third-degree relative among other samples from the same river, often taken at different times. Taking advantage of a sampled family quartet, we estimated the de novo mutation rate in the platypus at 7.0 × 10-9/bp/generation (95% CI 4.1 × 10-9-1.2 × 10-8/bp/generation). We estimated effective population sizes of ancestral populations and haplotype sharing between current groupings, and found evidence for bottlenecks and long-term population decline in multiple regions, and early divergence between populations in different regions. This study demonstrates the power of whole-genome sequencing for studying natural populations of an evolutionarily important species.}, } @article {pmid29688543, year = {2018}, author = {Schweizer, RM and Durvasula, A and Smith, J and Vohr, SH and Stahler, DR and Galaverni, M and Thalmann, O and Smith, DW and Randi, E and Ostrander, EA and Green, RE and Lohmueller, KE and Novembre, J and Wayne, RK}, title = {Natural Selection and Origin of a Melanistic Allele in North American Gray Wolves.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1190-1209}, doi = {10.1093/molbev/msy031}, pmid = {29688543}, issn = {1537-1719}, support = {R35 GM119856/GM/NIGMS NIH HHS/United States ; }, abstract = {Pigmentation is often used to understand how natural selection affects genetic variation in wild populations since it can have a simple genetic basis, and can affect a variety of fitness-related traits (e.g., camouflage, thermoregulation, and sexual display). In gray wolves, the K locus, a β-defensin gene, causes black coat color via a dominantly inherited KB allele. The allele is derived from dog-wolf hybridization and is at high frequency in North American wolf populations. We designed a DNA capture array to probe the geographic origin, age, and number of introgression events of the KB allele in a panel of 331 wolves and 20 dogs. We found low diversity in KB, but not ancestral ky, wolf haplotypes consistent with a selective sweep of the black haplotype across North America. Further, North American wolf KB haplotypes are monophyletic, suggesting that a single adaptive introgression from dogs to wolves most likely occurred in the Northwest Territories or Yukon. We use a new analytical approach to date the origin of the KB allele in Yukon wolves to between 1,598 and 7,248 years ago, suggesting that introgression with early Native American dogs was the source. Using population genetic simulations, we show that the K locus is undergoing natural selection in four wolf populations. We find evidence for balancing selection, specifically in Yellowstone wolves, which could be a result of selection for enhanced immunity in response to distemper. With these data, we demonstrate how the spread of an adaptive variant may have occurred across a species' geographic range.}, } @article {pmid29688542, year = {2018}, author = {Kupczok, A and Neve, H and Huang, KD and Hoeppner, MP and Heller, KJ and Franz, CMAP and Dagan, T}, title = {Rates of Mutation and Recombination in Siphoviridae Phage Genome Evolution over Three Decades.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1147-1159}, pmid = {29688542}, issn = {1537-1719}, support = {281357//European Research Council/International ; }, abstract = {The evolution of asexual organisms is driven not only by the inheritance of genetic modification but also by the acquisition of foreign DNA. The contribution of vertical and horizontal processes to genome evolution depends on their rates per year and is quantified by the ratio of recombination to mutation. These rates have been estimated for bacteria; however, no estimates have been reported for phages. Here, we delineate the contribution of mutation and recombination to dsDNA phage genome evolution. We analyzed 34 isolates of the 936 group of Siphoviridae phages using a Lactococcus lactis strain from a single dairy over 29 years. We estimate a constant substitution rate of 1.9 × 10-4 substitutions per site per year due to mutation that is within the range of estimates for eukaryotic RNA and DNA viruses. The reconstruction of recombination events reveals a constant rate of five recombination events per year and 4.5 × 10-3 nucleotide alterations due to recombination per site per year. Thus, the recombination rate exceeds the substitution rate, resulting in a relative effect of recombination to mutation (r/m) of ∼24 that is homogenous over time. Especially in the early transcriptional region, we detect frequent gene loss and regain due to recombination with phages of the 936 group, demonstrating the role of the 936 group pangenome as a reservoir of genetic variation. The observed substitution rate homogeneity conforms to the neutral theory of evolution; hence, the neutral theory can be applied to phage genome evolution and also to genetic variation brought about by recombination.}, } @article {pmid29688541, year = {2018}, author = {Susko, E and Lincker, L and Roger, AJ}, title = {Accelerated Estimation of Frequency Classes in Site-Heterogeneous Profile Mixture Models.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1266-1283}, doi = {10.1093/molbev/msy026}, pmid = {29688541}, issn = {1537-1719}, abstract = {As a consequence of structural and functional constraints, proteins tend to have site-specific preferences for particular amino acids. Failing to adjust for heterogeneity of frequencies over sites can lead to artifacts in phylogenetic estimation. Site-heterogeneous mixture-models have been developed to address this problem. However, due to prohibitive computational times, maximum likelihood implementations utilize fixed component frequency vectors inferred from sequences in a database that are external to the alignment under analysis. Here, we propose a composite likelihood approach to estimation of component frequencies for a mixture model that directly uses the data from the alignment of interest. In the common case that the number of taxa under study is not large, several adjustments to the default composite likelihood are shown to be necessary. In simulations, the approach is shown to provide large improvements over hierarchical clustering. For empirical data, substantial improvements in likelihoods are found over mixtures using fixed components.}, } @article {pmid29688540, year = {2018}, author = {Vieira, MC and Zinder, D and Cobey, S}, title = {Selection and Neutral Mutations Drive Pervasive Mutability Losses in Long-Lived Anti-HIV B-Cell Lineages.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1135-1146}, pmid = {29688540}, issn = {1537-1719}, support = {DP2 AI117921/AI/NIAID NIH HHS/United States ; }, abstract = {High-affinity antibodies arise within weeks of infection from the evolution of B-cell receptors under selection to improve antigen recognition. This rapid adaptation is enabled by the distribution of highly mutable "hotspot" motifs in B-cell receptor genes. High mutability in antigen-binding regions (complementarity determining regions [CDRs]) creates variation in binding affinity, whereas low mutability in structurally important regions (framework regions [FRs]) may reduce the frequency of destabilizing mutations. During the response, loss of mutational hotspots and changes in their distribution across CDRs and FRs are predicted to compromise the adaptability of B-cell receptors, yet the contributions of different mechanisms to gains and losses of hotspots remain unclear. We reconstructed changes in anti-HIV B-cell receptor sequences and show that mutability losses were ∼56% more frequent than gains in both CDRs and FRs, with the higher relative mutability of CDRs maintained throughout the response. At least 21% of the total mutability loss was caused by synonymous mutations. However, nonsynonymous substitutions caused most (79%) of the mutability loss in CDRs. Because CDRs also show strong positive selection, this result suggests that selection for mutations that increase binding affinity contributed to loss of mutability in antigen-binding regions. Although recurrent adaptation to evolving viruses could indirectly select for high mutation rates, we found no evidence of indirect selection to increase or retain hotspots. Our results suggest mutability losses are intrinsic to both the neutral and adaptive evolution of B-cell populations and might constrain their adaptation to rapidly evolving pathogens such as HIV and influenza.}, } @article {pmid29688526, year = {2018}, author = {Arkhipova, IR}, title = {Neutral Theory, Transposable Elements, and Eukaryotic Genome Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1332-1337}, doi = {10.1093/molbev/msy083}, pmid = {29688526}, issn = {1537-1719}, support = {R01 GM111917/GM/NIGMS NIH HHS/United States ; }, abstract = {Among the multitude of papers published yearly in scientific journals, precious few publications may be worth looking back in half a century to appreciate the significance of the discoveries that would later become common knowledge and get a chance to shape a field or several adjacent fields. Here, Kimura's fundamental concept of neutral mutation-random drift, which was published 50 years ago, is re-examined in light of its pervasive influence on comparative genomics and, more specifically, on the contribution of transposable elements to eukaryotic genome evolution.}, } @article {pmid29688518, year = {2018}, author = {Lee, J and Yang, EC and Graf, L and Yang, JH and Qiu, H and Zelzion, U and Chan, CX and Stephens, TG and Weber, APM and Boo, GH and Boo, SM and Kim, KM and Shin, Y and Jung, M and Lee, SJ and Yim, HS and Lee, JH and Bhattacharya, D and Yoon, HS}, title = {Analysis of the Draft Genome of the Red Seaweed Gracilariopsis chorda Provides Insights into Genome Size Evolution in Rhodophyta.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1869-1886}, doi = {10.1093/molbev/msy081}, pmid = {29688518}, issn = {1537-1719}, abstract = {Red algae (Rhodophyta) underwent two phases of large-scale genome reduction during their early evolution. The red seaweeds did not attain genome sizes or gene inventories typical of other multicellular eukaryotes. We generated a high-quality 92.1 Mb draft genome assembly from the red seaweed Gracilariopsis chorda, including methylation and small (s)RNA data. We analyzed these and other Archaeplastida genomes to address three questions: 1) What is the role of repeats and transposable elements (TEs) in explaining Rhodophyta genome size variation, 2) what is the history of genome duplication and gene family expansion/reduction in these taxa, and 3) is there evidence for TE suppression in red algae? We find that the number of predicted genes in red algae is relatively small (4,803-13,125 genes), particularly when compared with land plants, with no evidence of polyploidization. Genome size variation is primarily explained by TE expansion with the red seaweeds having the largest genomes. Long terminal repeat elements and DNA repeats are the major contributors to genome size growth. About 8.3% of the G. chorda genome undergoes cytosine methylation among gene bodies, promoters, and TEs, and 71.5% of TEs contain methylated-DNA with 57% of these regions associated with sRNAs. These latter results suggest a role for TE-associated sRNAs in RNA-dependent DNA methylation to facilitate silencing. We postulate that the evolution of genome size in red algae is the result of the combined action of TE spread and the concomitant emergence of its epigenetic suppression, together with other important factors such as changes in population size.}, } @article {pmid29688514, year = {2018}, author = {Kumar, S and Patel, R}, title = {Neutral Theory, Disease Mutations, and Personal Exomes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1297-1303}, pmid = {29688514}, issn = {1537-1719}, support = {R01 LM012487/LM/NLM NIH HHS/United States ; }, abstract = {Genetic differences between species and within populations are two sides of the same coin under the neutral theory of molecular evolution. This theory posits that a vast majority of evolutionary substitutions, which appear as differences between species, are (nearly) neutral, that is, these substitutions are permitted without a significantly adverse impact on a species' survival. We refer to them as evolutionarily permissible (ePerm) variation. Evolutionary permissibility of any possible variant can be inferred from multispecies sequence alignments by applying sophisticated statistical methods to the evolutionary tree of species. Here, we explore the evolutionary permissibility of amino acid variants associated with genetic diseases and those observed in personal exomes. Consistent with the predictions of the neutral theory, disease associated amino acid variants are rarely ePerm, much more biochemically radical, and found predominantly at more conserved positions than their non-disease counterparts. Only 10% of amino acid mutations are ePerm, but these variants rise to become two-thirds of all substitutions in the human lineage (a 6-fold enrichment). In contrast, only a minority of the variants in a personal exome are ePerm, a seemingly counterintuitive pattern that results from a combination of mutational and evolutionary processes that are, in fact, broadly consistent with the neutral theory. Evolutionarily forbidden variants outnumber detrimental variants in individual exomes and may play an underappreciated role in protecting against disease. We discuss these observations and conclude that the long-term evolutionary history of species can illuminate functional biomedical properties of variation present in personal exomes.}, } @article {pmid29688501, year = {2018}, author = {Yannai, A and Katz, S and Hershberg, R}, title = {The Codon Usage of Lowly Expressed Genes Is Subject to Natural Selection.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1237-1246}, pmid = {29688501}, issn = {1759-6653}, mesh = {Amino Acids/genetics ; Ampicillin/pharmacology ; Codon/*genetics ; Conserved Sequence ; Databases, Genetic ; Enterobacteriaceae/genetics ; Escherichia coli/drug effects/*genetics ; Escherichia coli Proteins/genetics ; Evolution, Molecular ; Genes, Bacterial/*genetics ; Genetic Fitness ; Protein Biosynthesis/genetics ; *Selection, Genetic ; Silent Mutation ; beta-Lactamases/genetics ; }, abstract = {Codon usage bias affects the genomes of organisms from all kingdoms of life and results from both background substitution biases and natural selection. Natural selection on codon usage to increase translation accuracy and efficiency has long been known to affect gene sequences. Such selection is stronger on highly, compared with lowly expressed genes, resulting in higher levels of codon bias within genes with higher expression levels. Additionally, selection on translation accuracy affects more strongly codons encoding conserved amino acids, since these will more often affect protein folding and/or function. By applying tests of selection on the gene sequences of the bacterium Escherichia coli, we demonstrate that both highly and lowly expressed genes display signals of selection on codon usage. Such signals are found for both conserved and less conserved amino acid positions, even within the 10% of E. coli genes expressed at the lowest levels. We further demonstrate experimentally that single synonymous codon replacements within a lowly expressed, essential gene can carry substantial effects on bacterial fitness. Combined, our results demonstrate that even within genes expressed at relatively low levels there is substantial selection on codon usage and that single synonymous codon replacements within such genes can have a marked effect on bacterial fitness.}, } @article {pmid29688499, year = {2018}, author = {Choe, YH and Kim, M and Woo, J and Lee, MJ and Lee, JI and Lee, EJ and Lee, YK}, title = {Comparing rock-inhabiting microbial communities in different rock types from a high arctic polar desert.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy070}, pmid = {29688499}, issn = {1574-6941}, abstract = {Although rocks are habitable places for microbes in extreme environments, microbial diversity in these lithic environments is still poorly understood. The diversity and abundance of rock-inhabiting microbial communities in different types of rock in Svalbard, Norwegian High Arctic were examined using NGS sequencing of bacterial 16S rRNA genes and fungal 28S rRNA genes. Compositions of both bacterial and fungal communities varied across different rock types: sandstone, limestone, basalt, granite and travertine. Bacterial communities were dominated by Actinobacteria, Proteobacteria, Chloroflexi, Bacteroidetes and Acidobacteria. Fungal communities consisted of Eurotiomycetes, Lecanoromycetes, Dothideomycetes and Leotiomycetes. Both bacterial and fungal community compositions were significantly correlated with the geochemical characteristics of rocks. Bacterial communities were considerably correlated with the rock elements such as Mg and Ca. Fungal communities were considerably correlated with Fe. Interestingly, many dominant bacterial and fungal operational taxonomic units in the investigated rocks from the study area were closely affiliated to those found in other cold regions such as Alpine area, Arctic and Antarctica, suggesting that environmental constraints such as cold temperature may lead to convergence in microbial community composition. These results confirm that rocks in cold environments act as reservoirs of diverse bacteria and fungi, which may improve our understanding of lithic microbial ecology in the cold desert.}, } @article {pmid29688481, year = {2018}, author = {Frost, SDW and Magalis, BR and Kosakovsky Pond, SL}, title = {Neutral Theory and Rapidly Evolving Viral Pathogens.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1348-1354}, pmid = {29688481}, issn = {1537-1719}, support = {R01 AI134384/AI/NIAID NIH HHS/United States ; R01 GM093939/GM/NIGMS NIH HHS/United States ; U01 GM110749/GM/NIGMS NIH HHS/United States ; }, abstract = {The evolution of viral pathogens is shaped by strong selective forces that are exerted during jumps to new hosts, confrontations with host immune responses and antiviral drugs, and numerous other processes. However, while undeniably strong and frequent, adaptive evolution is largely confined to small parts of information-packed viral genomes, and the majority of observed variation is effectively neutral. The predictions and implications of the neutral theory have proven immensely useful in this context, with applications spanning understanding within-host population structure, tracing the origins and spread of viral pathogens, predicting evolutionary dynamics, and modeling the emergence of drug resistance. We highlight the multiple ways in which the neutral theory has had an impact, which has been accelerated in the age of high-throughput, high-resolution genomics.}, } @article {pmid29688462, year = {2018}, author = {Nekrutenko, A and Team, G and Goecks, J and Taylor, J and Blankenberg, D}, title = {Biology Needs Evolutionary Software Tools: Let's Build Them Right.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1372-1375}, pmid = {29688462}, issn = {1537-1719}, support = {R01 AI134384/AI/NIAID NIH HHS/United States ; U41 HG006620/HG/NHGRI NIH HHS/United States ; }, abstract = {Research in population genetics and evolutionary biology has always provided a computational backbone for life sciences as a whole. Today evolutionary and population biology reasoning are essential for interpretation of large complex datasets that are characteristic of all domains of today's life sciences ranging from cancer biology to microbial ecology. This situation makes algorithms and software tools developed by our community more important than ever before. This means that we, developers of software tool for molecular evolutionary analyses, now have a shared responsibility to make these tools accessible using modern technological developments as well as provide adequate documentation and training.}, } @article {pmid29688454, year = {2018}, author = {Gong, X and Garcia-Robledo, E and Lund, MB and Lehner, P and Borisov, SM and Klimant, I and Revsbech, NP and Schramm, A}, title = {Gene expression of terminal oxidases in two marine bacterial strains exposed to nanomolar oxygen concentrations.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {7}, pages = {}, doi = {10.1093/femsec/fiy072}, pmid = {29688454}, issn = {1574-6941}, abstract = {The final step of aerobic respiration is carried out by a terminal oxidase transporting electrons to oxygen (O2). Prokaryotes harbor diverse terminal oxidases that differ in phylogenetic origin, structure, biochemical function, and affinity for O2. Here we report on the expression of high-affinity (cytochrome cbb3 oxidase), low-affinity (cytochrome aa3 oxidase), and putative low-affinity (cyanide-insensitive oxidase (CIO)) terminal oxidases in the marine bacteria Idiomarina loihiensis L2-TR and Marinobacter daepoensis SW-156 upon transition to very low O2 concentrations (<200 nM), measured by RT-qPCR. In both strains, high-affinity cytochrome cbb3 oxidase showed the highest expression levels and was significantly up-regulated upon transition to low O2 concentrations. Low-affinity cytochrome aa3 oxidase showed very low transcription levels throughout the incubation. Surprisingly, however, it was also up-regulated upon transition to low O2 concentrations. In contrast, putative low-affinity CIO had much lower expression levels and markedly different regulation patterns between the two strains. These results demonstrate that exposure to low O2 concentrations regulates the gene expression of different types of terminal oxidases, but also that the type and magnitude of transcriptional response is species-dependent. Therefore, in situ transcriptome data cannot, without detailed knowledge of the transcriptional regulation of the species involved, be translated into relative respiratory activity.}, } @article {pmid29688430, year = {2018}, author = {Zhao, Y and Lin, P and Liufu, Z and Yang, H and Lyu, Y and Shen, X and Wu, CI and Tang, T}, title = {Regulation of Large Number of Weak Targets-New Insights from Twin-microRNAs.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1255-1264}, pmid = {29688430}, issn = {1759-6653}, mesh = {Animals ; Conserved Sequence ; Drosophila melanogaster/genetics ; *Evolution, Molecular ; Gene Expression ; *Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Genes, Insect/genetics ; MicroRNAs/biosynthesis/*genetics ; Sequence Analysis, RNA ; Small Molecule Libraries ; }, abstract = {Each animal microRNA (miRNA) targets many genes for repression. Down-regulation of most of these targets is weak and has no detectable individual phenotypic effect. Whether this extensive weak repression is biologically relevant is a central issue in the debate on miRNA functionality. In the "small (target) pool" view, weak repression is nonfunctional and should be gradually removed during evolution. However, since the selective advantage of removing individual targets is small, testing this hypothesis is a challenge. We propose a novel approach by using miRNAs we call twin-miRs, which produce two mature products from the hairpin of the same miRNA precursor. Loss of the minor miR partner would affect all its targets and thus could be visible to selection. Since the minor miRs repress all their targets weakly, the "small pool" hypothesis would predict the elimination of twin-miRs over time. Surveying and sequencing 45 small RNA libraries in Drosophila, we found that nearly 40% of miRNAs produce twin-miRs. The minor forms are expressed in nontrivial abundance and repress their targets weakly. Interestingly, twin-miRs are often evolutionarily old, highly conserved, and comparable to solo-miRs in expression. Since there is no measurable trend toward reduction in target pool size, we conclude that at least some of the weak repression interactions are functional. A companion study using the May-Wigner theory of network stability suggests that distributed weak repression cumulatively contributes to stability of gene regulatory networks.}, } @article {pmid29688427, year = {2018}, author = {Gallart, M and Adair, KL and Love, J and Meason, DF and Clinton, PW and Xue, J and Turnbull, MH}, title = {Genotypic variation in Pinus radiata responses to nitrogen source are related to changes in the root microbiome.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy071}, pmid = {29688427}, issn = {1574-6941}, abstract = {Variation in traits within a plant species contributes to differences in soil physicochemistry and rhizosphere microbial communities. However, how intraspecific variation in plant responses to nitrogen (N) shapes these communities remains unclear. We studied whether plant responses to organic and inorganic N forms vary among genotypes, and if these responses were associated with variation in root-associated communities. We investigated how the root microbiomes of two Pinus radiata D. Don genotypes were altered by two years of N-fertilisation in field conditions. We characterised rhizosphere bacterial and fungal communities, as well as root-associated fungal communities, of trees receiving yearly additions of NH4NO3 or L-arginine, and control trees. We also measured plant traits and rhizosphere soil physicochemical properties. Two main findings emerged: (i) N form and tree genotype affected soil physicochemical properties as well as plant measures, and these responses were associated with variation in microbial communities, and (ii) rhizosphere and root-associated communities differed in their responses to N form and host genotype. Our results suggest that N forms have different influences on N and carbon dynamics at the plant-soil interface by inducing root-mediated responses that are associated with shifts in the root microbiome such that communities more closely associated with roots are more sensitive to genotype-specific responses.}, } @article {pmid29688426, year = {2018}, author = {Caspermeyer, J}, title = {First Population-Scale Sequencing Project Explores Platypus History.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy063}, pmid = {29688426}, issn = {1537-1719}, } @article {pmid29688421, year = {2018}, author = {Xue, AT and Ruggiero, RP and Hickerson, MJ and Boissinot, S}, title = {Differential Effect of Selection against LINE Retrotransposons among Vertebrates Inferred from Whole-Genome Data and Demographic Modeling.}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1265-1281}, pmid = {29688421}, issn = {1759-6653}, support = {R15 GM096267/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Demography ; *Evolution, Molecular ; Genetics, Population ; Genome ; *Genomics ; Humans ; Long Interspersed Nucleotide Elements/*genetics ; Mammals/genetics ; Mice ; Models, Genetic ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Retroelements/genetics ; *Selection, Genetic ; }, abstract = {Variation in LINE composition is one of the major determinants for the substantial size and structural differences among vertebrate genomes. In particular, the larger genomes of mammals are characterized by hundreds of thousands of copies from a single LINE clade, L1, whereas nonmammalian vertebrates possess a much greater diversity of LINEs, yet with orders of magnitude less in copy number. It has been proposed that such variation in copy number among vertebrates is due to differential effect of LINE insertions on host fitness. To investigate LINE selection, we deployed a framework of demographic modeling, coalescent simulations, and probabilistic inference against population-level whole-genome data sets for four model species: one population each of threespine stickleback, green anole, and house mouse, as well as three human populations. Specifically, we inferred a null demographic background utilizing SNP data, which was then exploited to simulate a putative null distribution of summary statistics that was compared with LINE data. Subsequently, we applied the inferred null demographic model with an additional exponential size change parameter, coupled with model selection, to test for neutrality as well as estimate the strength of either negative or positive selection. We found a robust signal for purifying selection in anole and mouse, but a lack of clear evidence for selection in stickleback and human. Overall, we demonstrated LINE insertion dynamics that are not in accordance to a mammalian versus nonmammalian dichotomy, and instead the degree of existing LINE activity together with host-specific demographic history may be the main determinants of LINE abundance.}, } @article {pmid29688331, year = {2018}, author = {Ridley, CM and Voordouw, G}, title = {Aerobic microbial taxa dominate deep subsurface cores from the Alberta oil sands.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy073}, pmid = {29688331}, issn = {1574-6941}, abstract = {Little is known about the microbial ecology of the subsurface oil sands in Northern Alberta, Canada. Biodegradation of low molecular weight hydrocarbons by indigenous microbes has enriched high molecular weight hydrocarbons, resulting in highly viscous bitumen. This extreme subsurface environment is further characterized by low nutrient availability and limited access to water, thus resulting in low microbial biomass. Improved DNA isolation protocols and increasingly sensitive sequencing methods have allowed an in-depth investigation of the microbial ecology of this unique subsurface environmental niche. Community analysis was performed on core samples (n = 62) that were retrieved from two adjacent sites located in the Athabasca Oil Sands at depths from 220 to 320 m below the surface. Microbial communities were dominated by aerobic taxa, including Pseudomonas and Acinetobacter. Only one core sample microbial community was dominated by anaerobic taxa, including the methanogen Methanoculleus, as well as Desulfomicrobium and Thauera. Although the temperature of the bitumen-containing subsurface is low (8°C), two core samples had high fractions of the potentially thermophilic taxon, Thermus. Predominance of aerobic taxa in the subsurface suggests the potential for in situ aerobic hydrocarbon degradation; however, more studies are required to determine the functional role of these taxa within this unique environment.}, } @article {pmid29688169, year = {2018}, author = {Xu, B and Hu, B and Wang, J and Lan, Y and Zhu, Y and Dai, X and Huang, L and Huang, Y and Du, W}, title = {Virgibacillus indicus sp. nov. and Virgibacillus profundi sp. nov, two moderately halophilic bacteria isolated from marine sediment by using microfluidic streak plates.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2015-2023}, doi = {10.1099/ijsem.0.002782}, pmid = {29688169}, issn = {1466-5034}, mesh = {Archaea/genetics ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Indian Ocean ; Microfluidics ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Virgibacillus/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Three Gram-variable, moderately halophilic, motile, endospore-forming rods, designated P2-C2T, P3-H5T and P3-B8, were isolated from marine sediment of the Southwest Indian Ocean by using the microfluidic streak plate method. Phylogeny based on 16S rRNA gene sequences showed that strains P2-C2T and P3-H5T formed a robust cluster within the genus Virgibacillus and exhibited 16S rRNA gene similarity levels of 95.3-96.8 and 94.9-96.3 % to the type strains of Virgibacillus species, respectively. The 16S rRNA gene similarity between P2-C2T and P3-H5T was 97.6 %. Strain P3-B8 has an identical 16S rRNA gene sequence to strain P3-H5T. For all the novel strains, the predominant cellular fatty acids were anteiso-C15 : 0 and anteiso-C17 : 0, the main menaquinone was MK-7, and the polar lipid profiles contained diphosphatidylglycerol and phosphatidylglycerol. The genomic DNA G+C contents of strains P2-C2T, P3-H5T and P3-B8 were 38.3, 37.3 and 37.5 mol%, respectively. Combined data from phenotypic and genotypic studies demonstrated that strains P2-C2T and P3-H5T/P3-B8 are representatives of two different novel species of the genus Virgibacillus, for which the name Virgibacillus indicus sp. nov. and Virgibacillusprofundi are proposed. The type strains are P2-C2T (=CGMCC 1.16138T=NBRC 113014T) and P3-H5T (=CGMCC 1.16139T=NBRC 113015T).}, } @article {pmid29688168, year = {2018}, author = {Dijkshoorn, L}, title = {International Committee on Systematics of Prokaryotes. Minutes of the meetings, 7, 8 and 9 July 2017, Valencia, Spain.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2104-2110}, doi = {10.1099/ijsem.0.002787}, pmid = {29688168}, issn = {1466-5034}, } @article {pmid29688167, year = {2018}, author = {Brown, DR}, title = {Notice of impending dissolution of inactive Subcommittees on Taxonomy.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2102-2103}, doi = {10.1099/ijsem.0.002587}, pmid = {29688167}, issn = {1466-5034}, } @article {pmid29688166, year = {2018}, author = {Goldberg, SR and Haltli, BA and Correa, H and Kerr, RG}, title = {Description of Sansalvadorimonas verongulae gen. nov., sp. nov., a gammaproteobacterium isolated from the marine sponge Verongula gigantea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2006-2014}, doi = {10.1099/ijsem.0.002781}, pmid = {29688166}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Bahamas ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Porifera/*microbiology ; Quinones/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, strictly aerobic, motile, rod-shaped bacterium, designated strain RKSG058T, was isolated from the marine sponge Verongula gigantea, collected off the west coast of San Salvador, The Bahamas. Phylogenetic analyses based on 16S rRNA gene sequences revealed that RKSG058T formed a distinct lineage within the family Hahellaceae (order Oceanospirillales, class Gammaproteobacteria), and was most closely related to the genus Endozoicomonas, with sequence similarities to members of this genus ranging from 92.0 to 93.7 %. Optimal growth occurred at 30 °C, at pH 7 and in the presence of 2-3 % (w/v) NaCl. The predominant cellular fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The major and minor respiratory quinones were Q-9 and Q-8, respectively. The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, three unidentified aminolipids, an unidentified phospholipid and five unidentified lipids. The DNA G+C content was 42.3 mol%. Biochemical, chemotaxonomic and phylogenetic analyses indicated that strain RKSG058T represents the first cultured isolate of a novel bacterial genus and species within the family Hahellaceae, for which the name Sansalvadorimonas verongulae gen. nov., sp. nov. is proposed. The type strain of Sansalvadorimonas verongulae is RKSG058T (=TSD-72T=LMG 29871T). An emended description of the genus Kistimonas is provided.}, } @article {pmid29688165, year = {2018}, author = {de Vega, C and Albaladejo, RG and Lachance, MA}, title = {Metschnikowia maroccana f.a., sp. nov., a new yeast species associated with floral nectar from Morocco.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2028-2035}, doi = {10.1099/ijsem.0.002784}, pmid = {29688165}, issn = {1466-5034}, mesh = {Biodiversity ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Flowers ; Iridaceae/microbiology ; Metschnikowia/*classification/genetics/isolation & purification ; Morocco ; *Phylogeny ; *Plant Nectar ; Sequence Analysis, DNA ; Teucrium/microbiology ; }, abstract = {Wild flowers, and in particular, nectar of flowers, have been shown to be a rich reservoir of yeast biodiversity. In a taxonomic study of yeasts recovered from floral nectar in Morocco, nine strains were found to represent a novel species. Morphological and physiological characteristics and sequence analyses of the D1/D2 region of the large subunit rRNA gene as well as the internal transcribed spacer region showed that the novel species belonged to the genus Metschnikowia. The name Metschnikowia maroccana f.a., sp. nov. (EBDCdVMor24-1T=CBS 15053T=NRRL Y-63972T) is proposed to accommodate this new species. Metschnikowia maroccana was isolated from floral nectar of Teucrium pseudochamaepitys, Teucrium polium and Gladiolus italicus. The ascosporic state of the novel species was not found. Metschnikowia maroccana was phylogenetically distinct from any currently recognized species and forms a well-supported subclade (bootstrap value 81 %) containing species associated with flowers and flower-visiting insects, including Metschnikowia gruessii, Metschnikowia lachancei and Metschnikowia vanudenii. The close genealogical relationship of M. maroccana with the M. gruessii clade is also consistent with the striking similarity of their 'aeroplane' cells morphologies and the lack of utilization of the α-glucoside trehalose. The ecology of these novel species and its probable endemicity are discussed.}, } @article {pmid29688164, year = {2018}, author = {Pitt, A and Schmidt, J and Lang, E and Whitman, WB and Woyke, T and Hahn, MW}, title = {Polynucleobacter meluiroseus sp. nov., a bacterium isolated from a lake located in the mountains of the Mediterranean island of Corsica.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1975-1985}, pmid = {29688164}, issn = {1466-5034}, support = {P 27160//Austrian Science Fund FWF/Austria ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; Burkholderiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; France ; Islands ; Lakes/*microbiology ; Mediterranean Islands ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Strain AP-Melu-1000-B4 was isolated from a lake located in the mountains of the Mediterranean island of Corsica (France). Phenotypic, chemotaxonomic and genomic traits were investigated. Phylogenetic analyses based on 16S rRNA gene sequencing referred the strain to the cryptic species complex PnecC within the genus Polynucleobacter. The strain encoded genes for biosynthesis of proteorhodopsin and retinal. When pelleted by centrifugation the strain showed an intense rose colouring. Major fatty acids were C16 : 1ω7c, C16 : 0, C18 : 1ω7c and summed feature 2 (C16 : 1 isoI and C14 : 0-3OH). The sequence of the 16S rRNA gene contained an indel which was not present in any previously described Polynucleobacter species. Genome sequencing revealed a genome size of 1.89 Mbp and a G+C content of 46.6 mol%. In order to resolve the phylogenetic position of the new strain within subcluster PnecC, its phylogeny was reconstructed from sequences of 319 shared genes. To represent all currently described Polynucleobacter species by whole genome sequences, three type strains were additionally sequenced. Our phylogenetic analysis revealed that strain AP-Melu-100-B4 occupied a basal position compared with previously described PnecC strains. Pairwise determined whole genome average nucleotide identity (gANI) values suggested that strain AP-Melu-1000-B4 represents a new species, for which we propose the name Polynucleobacter meluiroseus sp. nov. with the type strain AP-Melu-1000-B4T (=DSM 103591T=CIP 111329T).}, } @article {pmid29687664, year = {2018}, author = {Grafe, M and Goers, M and von Tucher, S and Baum, C and Zimmer, D and Leinweber, P and Vestergaard, G and Kublik, S and Schloter, M and Schulz, S}, title = {Bacterial potentials for uptake, solubilization and mineralization of extracellular phosphorus in agricultural soils are highly stable under different fertilization regimes.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {320-327}, doi = {10.1111/1758-2229.12651}, pmid = {29687664}, issn = {1758-2229}, abstract = {Phosphorus is one of the most important macronutrient for plants. In agriculture, amending fertilizer with phosphorus (P) is common practice. However, natural phosphorus sources are finite, making research for more sustainable management practices necessary. We postulated that the addition of carbon (C) and nitrogen (N) would stimulate phosphorus mobilization by bacteria because of their desire to maintain a stable intracellular C:N:P stoichiometry. Therefore, we chose a metagenomic approach to investigate two agricultural soils, which only received mineral N fertilizer or mineral N and organic fertilizer for more than 20 years. The most abundant genes involved in the acquisition of external P sources in our study were those involved in solubilization and subsequent uptake of inorganic phosphorus. Independent of site and season, the relative abundance of genes involved in P turnover was not significantly affected by the addition of fertilizers. However, the type of fertilization had a significant impact on the diversity pattern of bacterial families harbouring genes coding for the different P transformation processes. This gives rise to the possibility that fertilizers can substantially change phosphorus turnover efficiency by favouring different families. Additionally, none of the families involved in phosphorus turnover covered all investigated processes. Therefore, promoting bacteria which play an essential role specifically in mobilization of hardly accessible phosphorus could help to secure the phosphorus supply of plants in soils with low P input.}, } @article {pmid29687657, year = {2018}, author = {Pandey, SS and Patnana, PK and Padhi, Y and Chatterjee, S}, title = {Low-iron conditions induces the hypersensitive reaction and pathogenicity hrp genes expression in Xanthomonas and is involved in modulation of hypersensitive response and virulence.}, journal = {Environmental microbiology reports}, volume = {10}, number = {5}, pages = {522-531}, doi = {10.1111/1758-2229.12650}, pmid = {29687657}, issn = {1758-2229}, abstract = {Expression of hrp (hypersensitive reaction and pathogenicity) genes inside the host is crucial for virulence of phytopathogenic bacteria. The hrp genes encode components of type3 secretion system (T3SS), HR elicitors and several regulators, which are involved in the co-ordinated expression of hrp genes in the host environment and in hrp inducing chemically defined medium. However, little is known about specific host or environmental factors which may play a role in the induction of hrp gene expression. In this study, we show that iron-limiting condition elicits induced expression of hrp genes, including type3 secretion system (T3SS) and effectors (T3E). Expression analysis using qRT-PCR and promoter probe strains suggest significant induction in the expression of Hrp and T3S-associated genes of Xanthomonas campestris pv. campestris (Xcc) under low-iron condition, and is suppressed by exogenous supplementation of iron. Furthermore, we show that with exogenous iron supplementation, wild type Xcc exhibited reduced disease symptoms in host-plant, and exhibited significant reduction in HR and callose deposition in the non-host plants. Xanthomonas oryzae and oryzicola pathovars also exhibited the iron affect, albeit to a lesser extend compared with the Xcc. Overall, our results suggest that low-iron condition inside the host may play a crucial role in pathogenicity.}, } @article {pmid29687636, year = {2018}, author = {Liu, J and Zhang, W and Du, H and Leng, X and Li, JH and Pan, H and Xu, J and Wu, LF and Xiao, T}, title = {Seasonal changes in the vertical distribution of two types of multicellular magnetotactic prokaryotes in the sediment of Lake Yuehu, China.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {475-484}, doi = {10.1111/1758-2229.12652}, pmid = {29687636}, issn = {1758-2229}, abstract = {There are two genetically distinct morphological types of multicellular magnetotactic prokaryotes (MMPs) in the intertidal zone of Lake Yuehu (China): ellipsoidal MMPs (eMMPs) and spherical MMPs (sMMPs). We studied the vertical distribution of both types of MMPs in the sediment at Lake Yuehu during 1 year. Both types of MMPs were observed at sediment depths ranging from 1 to 34 cm, depending on the seasons. The eMMPs distributed at depths of 2-34 cm during spring, 1-11 cm during summer, 2-21 cm during autumn and 9-32 cm during winter. The eMMP species Candidatus Magnetananas rongchenensis, with magnetite magnetosomes, dominated at all distribution depths. These results suggested that Ca. M. rongchenensis migrated vertically during four seasons. The vertical profiles of oxidation-reduction potential (ORP) in Lake Yuehu changed seasonally, and these changes coincided with the seasonal distribution of MMPs, suggesting that the ORP affected the vertical distribution of MMPs. In addition, high concentrations of ammonium and silicate were associated with low abundances of MMPs.}, } @article {pmid29687624, year = {2018}, author = {Rutherford, V and Yom, K and Ozer, EA and Pura, O and Hughes, A and Murphy, KR and Cudzilo, L and Mitchell, D and Hauser, AR}, title = {Environmental reservoirs for exoS+ and exoU+ strains of Pseudomonas aeruginosa.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {485-492}, pmid = {29687624}, issn = {1758-2229}, support = {K24 AI104831/AI/NIAID NIH HHS/United States ; R01 AI053674/AI/NIAID NIH HHS/United States ; R01 AI118257/AI/NIAID NIH HHS/United States ; U19 AI135964/AI/NIAID NIH HHS/United States ; }, abstract = {Pseudomonas aeruginosa uses its type III secretion system to inject the effector proteins ExoS and ExoU into eukaryotic cells, which subverts these cells to the bacterium's advantage and contributes to severe infections. We studied the environmental reservoirs of exoS+ and exoU+ strains of P. aeruginosa by collecting water, soil, moist substrates and plant samples from environments in the Chicago region and neighbouring states. Whole-genome sequencing was used to determine the phylogeny and type III secretion system genotypes of 120 environmental isolates. No correlation existed between geographic separation of isolates and their genetic relatedness, which confirmed previous findings of both high genetic diversity within a single site and the widespread distribution of P. aeruginosa clonal complexes. After excluding clonal isolates cultured from the same samples, 74 exoS+ isolates and 16 exoU+ isolates remained. Of the exoS+ isolates, 41 (55%) were from natural environmental sites and 33 (45%) were from man-made sites. Of the exoU+ isolates, only 3 (19%) were from natural environmental sites and 13 (81%) were from man-made sites (p < 0.05). These findings suggest that man-made water systems may be a reservoir from which patients acquire exoU+ P. aeruginosa strains.}, } @article {pmid29687609, year = {2018}, author = {Zhang, Q and Goberna, M and Liu, Y and Cui, M and Yang, H and Sun, Q and Insam, H and Zhou, J}, title = {Competition and habitat filtering jointly explain phylogenetic structure of soil bacterial communities across elevational gradients.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2386-2396}, doi = {10.1111/1462-2920.14247}, pmid = {29687609}, issn = {1462-2920}, abstract = {The importance of assembly processes in shaping biological communities is poorly understood, especially for microbes. Here, we report on the forces that structure soil bacterial communities along a 2000 m elevational gradient. We characterized the relative importance of habitat filtering and competition on phylogenetic structure and turnover in bacterial communities. Bacterial communities exhibited a phylogenetically clustered pattern and were more clustered with increasing elevation. Biotic factors (i.e., relative abundance of dominant bacterial lineages) appeared to be most important to the degree of clustering, evidencing the role of the competitive ability of entire clades in shaping the communities. Phylogenetic turnover showed the greatest correlation to elevation. After controlling the elevation, biotic factors showed greater correlation to phylogenetic turnover than all the habitat variables (i.e., climate, soil and vegetation). Structural equation modelling also identified that elevation and soil organic matter exerted indirect effects on phylogenetic diversity and turnover by determining the dominance of microbial competitors. Our results suggest that competition among bacterial taxa induced by soil carbon contributes to the phylogenetic pattern across elevational gradient in the Tibetan Plateau. This highlights the importance of considering not only abiotic filtering but also biotic interactions in soil bacterial communities across stressful elevational gradients.}, } @article {pmid29687607, year = {2018}, author = {Kvarnemo, C}, title = {Why do some animals mate with one partner rather than many? A review of causes and consequences of monogamy.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1795-1812}, doi = {10.1111/brv.12421}, pmid = {29687607}, issn = {1469-185X}, support = {621-2008-5503//Vetenskapsrådet/International ; }, abstract = {Why do some animals mate with one partner rather than many? Here, I investigate factors related to (i) spatial constraints (habitat limitation, mate availability), (ii) time constraints (breeding synchrony, length of breeding season), (iii) need for parental care, and (iv) genetic compatibility, to see what support can be found in different taxa regarding the importance of these factors in explaining the occurrence of monogamy, whether shown by one sex (monogyny or monandry) or by both sexes (mutual monogamy). Focusing on reproductive rather than social monogamy whenever possible, I review the empirical literature for birds, mammals and fishes, with occasional examples from other taxa. Each of these factors can explain mating patterns in some taxa, but not in all. In general, there is mixed support for how well the factors listed above predict monogamy. The factor that shows greatest support across taxa is habitat limitation. By contrast, while a need for parental care might explain monogamy in freshwater fishes and birds, there is clear evidence that this is not the case in marine fishes and mammals. Hence, reproductive monogamy does not appear to have a single overriding explanation, but is more taxon specific. Genetic compatibility is a promising avenue for future work likely to improve our understanding of monogamy and other mating patterns. I also discuss eight important consequences of reproductive monogamy: (i) parentage, (ii) parental care, (iii) eusociality and altruism, (iv) infanticide, (v) effective population size, (vi) mate choice before mating, (vii) sexual selection, and (viii) sexual conflict. Of these, eusociality and infanticide have been subject to debate, briefly summarised herein. A common expectation is that monogamy leads to little sexual conflict and no or little sexual selection. However, as reviewed here, sexual selection can be substantial under mutual monogamy, and both sexes can be subject to such selection. Under long-term mutual monogamy, mate quality is obviously more important than mate numbers, which in turn affects the need for pre-mating mate choice. Overall, I conclude that, despite much research on genetic mating patterns, reproductive monogamy is still surprisingly poorly understood and further experimental and comparative work is needed. This review identifies several areas in need of more data and also proposes new hypotheses to test.}, } @article {pmid29687586, year = {2018}, author = {Meinhardt, KA and Stopnisek, N and Pannu, MW and Strand, SE and Fransen, SC and Casciotti, KL and Stahl, DA}, title = {Ammonia-oxidizing bacteria are the primary N2 O producers in an ammonia-oxidizing archaea dominated alkaline agricultural soil.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14246}, pmid = {29687586}, issn = {1462-2920}, abstract = {Most agricultural N2 O emissions are a consequence of microbial transformations of nitrogen (N) fertilizer, and mitigating increases in N2 O emission will depend on identifying microbial sources and variables influencing their activities. Here, using controlled microcosm and field studies, we found that synthetic N addition in any tested amount stimulated the production of N2 O from ammonia-oxidizing bacteria (AOB), but not archaea (AOA), from a bioenergy crop soil. The activities of these two populations were differentiated by N treatments, with abundance and activity of AOB increasing as nitrate and N2 O production increased. Moreover, as N2 O production increased, the isotopic composition of N2 O was consistent with an AOB source. Relative N2 O contributions by both populations were quantified using selective inhibitors and varying N availability. Complementary field analyses confirmed a positive correlation between N2 O flux and AOB abundance with N application. Collectively, our data indicate that AOB are the major N2 O producers, even with low N addition, and that better-metered N application, complemented by selective inhibitors, could reduce projected N2 O emissions from agricultural soils.}, } @article {pmid29687579, year = {2018}, author = {de Francisco, P and Martín-González, A and Turkewitz, AP and Gutiérrez, JC}, title = {Genome plasticity in response to stress in Tetrahymena thermophila: selective and reversible chromosome amplification and paralogous expansion of metallothionein genes.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2410-2421}, pmid = {29687579}, issn = {1462-2920}, support = {R01 GM105783/GM/NIGMS NIH HHS/United States ; }, abstract = {Extreme stress situations can induce genetic variations including genome reorganization. In ciliates like Tetrahymena thermophila, the approximately 45-fold ploidy of the somatic macronucleus may enable adaptive responses that depend on genome plasticity. To identify potential genome-level adaptations related to metal toxicity, we isolated three Tetrahymena thermophila strains after an extended adaptation period to extreme metal concentrations (Cd2+ , Cu2+ or Pb2+). In the Cd-adapted strain, we found a approximately five-fold copy number increase of three genes located in the same macronuclear chromosome, including two metallothionein genes, MTT1 and MTT3. The apparent amplification of this macronuclear chromosome was reversible and reproducible, depending on the presence of environmental metal. We also analysed three knockout (KO) and/or knockdown (KD) strains for MTT1 and/or MTT5. In the MTT5KD strain, we found at least two new genes arising from paralogous expansion of MTT1, which encode truncated variants of MTT1. The expansion can be explained by a model based on somatic recombination between MTT1 genes on pairs of macronuclear chromosomes. At least two of the new paralogs are transcribed and upregulated in response to Cd2+ . Altogether, we have thus identified two distinct mechanisms, both involving genomic plasticity in the polyploid macronucleus that may represent adaptive responses to metal-related stress.}, } @article {pmid29687575, year = {2018}, author = {Hu, HW and Wang, JT and Singh, BK and Liu, YR and Chen, YL and Zhang, YJ and He, JZ}, title = {Diversity of herbaceous plants and bacterial communities regulates soil resistome across forest biomes.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3186-3200}, doi = {10.1111/1462-2920.14248}, pmid = {29687575}, issn = {1462-2920}, support = {XDB15020200//Chinese Academy of Sciences/ ; DP170103628//Australian Research Council/ ; DE150100870//Australian Research Council/ ; 41601256//Natural Science Foundation of China/ ; }, abstract = {Antibiotic resistance is ancient and prevalent in natural ecosystems and evolved long before the utilization of synthetic antibiotics started, but factors influencing the large-scale distribution patterns of natural antibiotic resistance genes (ARGs) remain largely unknown. Here, a large-scale investigation over 4000 km was performed to profile soil ARGs, plant communities and bacterial communities from 300 quadrats across five forest biomes with minimal human impact. We detected diverse and abundant ARGs in forests, including over 160 genes conferring resistance to eight major categories of antibiotics. The diversity of ARGs was strongly and positively correlated with the diversity of bacteria, herbaceous plants and mobile genetic elements (MGEs). The ARG composition was strongly correlated with the taxonomic structure of bacteria and herbs. Consistent with this strong correlation, structural equation modelling demonstrated that the positive effects of bacterial and herb communities on ARG patterns were maintained even when simultaneously accounting for multiple drivers (climate, spatial predictors and edaphic factors). These findings suggest a paradigm that the interactions between aboveground and belowground communities shape the large-scale distribution of soil resistomes, providing new knowledge for tackling the emerging environmental antibiotic resistance.}, } @article {pmid29687572, year = {2018}, author = {Compte-Port, S and Borrego, CM and Moussard, H and Jeanbille, M and Restrepo-Ortiz, CX and de Diego, A and Rodriguez-Iruretagoiena, A and Gredilla, A and Fdez-Ortiz de Vallejuelo, S and Galand, PE and Kalenitchenko, D and Rols, JL and Pokrovsky, OS and Gonzalez, AG and Camarero, L and Muñiz, S and Navarro-Navarro, E and Auguet, JC}, title = {Metal contaminations impact archaeal community composition, abundance and function in remote alpine lakes.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2422-2437}, doi = {10.1111/1462-2920.14252}, pmid = {29687572}, issn = {1462-2920}, abstract = {Using the 16S rRNA and mcrA genes, we investigated the composition, abundance and activity of sediment archaeal communities within 18 high-mountain lakes under contrasted metal levels from different origins (bedrock erosion, past-mining activities and atmospheric depositions). Bathyarchaeota, Euryarchaeota and Woesearchaeota were the major phyla found at the meta-community scale, representing 48%, 18.3% and 15.2% of the archaeal community respectively. Metals were equally important as physicochemical variables in explaining the assemblage of archaeal communities and their abundance. Methanogenesis appeared as a process of central importance in the carbon cycle within sediments of alpine lakes as indicated by the absolute abundance of methanogen 16S rRNA and mcrA gene transcripts (105 to 109 copies g-1). We showed that methanogen abundance and activity were significantly reduced with increasing concentrations of Pb and Cd, two indicators of airborne metal contaminations. Considering the ecological importance of methanogenesis in sediment habitats, these metal contaminations may have system wide implications even in remote area such as alpine lakes. Overall, this work was pioneer in integrating the effect of long-range atmospheric depositions on archaeal communities and indicated that metal contamination might significantly compromise the contribution of Archaea to the carbon cycling of the mountain lake sediments.}, } @article {pmid29687563, year = {2018}, author = {Mathur, V and Del Campo, J and Kolisko, M and Keeling, PJ}, title = {Global diversity and distribution of close relatives of apicomplexan parasites.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2824-2833}, doi = {10.1111/1462-2920.14134}, pmid = {29687563}, issn = {1462-2920}, support = {MOP 42517//Canadian Institute for Health Research/ ; //Tula Foundation/ ; FP7-PEOPLE-2012-IOF - 331450 CAARL//Marie Curie Outgoing Fellowship/ ; }, abstract = {Apicomplexans are a group of obligate intracellular parasites, but their retention of a relict non-photosynthetic plastid reveals that they evolved from free-living photosynthetic ancestors. The closest relatives of apicomplexans include photosynthetic chromerid algae (e.g., Chromera and Vitrella), non-photosynthetic colpodellid predators (e.g., Colpodella) and several environmental clades collectively called Apicomplexan-Related Lineages (ARLs). Here we investigate the global distribution and inferred ecology of the ARLs by expansively searching for apicomplexan-related plastid small ribosomal subunit (SSU) genes in large-scale high-throughput bacterial amplicon surveys. Searching more than 220 million sequences from 224 geographical sites worldwide revealed 94 324 ARL plastid SSU sequences. Meta-analyses confirm that all ARLs are coral reef associated and not to marine environments generally, but only a subset is actually associated with coral itself. Most unexpectedly, Chromera was found exclusively in coral biogenous sediments, and not within coral tissue, indicating that it is not a coral symbiont, as typically thought. In contrast, ARL-V is the most diverse, geographically widespread and abundant of all ARL clades and is strictly associated with coral tissue and mucus. ARL-V was found in 19 coral species in reefs, including azooxanthellate corals at depths greater than 500 m. We suggest this is indicative of a parasitic or commensal relationship, and not of photosynthetic symbiosis, further underscoring the importance of isolating ARL-V and determining its relationship with the coral host.}, } @article {pmid29687554, year = {2018}, author = {LeTourneau, MK and Marshall, MJ and Cliff, JB and Bonsall, RF and Dohnalkova, AC and Mavrodi, DV and Devi, SI and Mavrodi, OV and Harsh, JB and Weller, DM and Thomashow, LS}, title = {Phenazine-1-carboxylic acid and soil moisture influence biofilm development and turnover of rhizobacterial biomass on wheat root surfaces.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14244}, pmid = {29687554}, issn = {1462-2920}, abstract = {Phenazine-1-carboxylic acid (PCA) is produced by rhizobacteria in dryland but not in irrigated wheat fields of the Pacific Northwest, USA. PCA promotes biofilm development in bacterial cultures and bacterial colonization of wheat rhizospheres. However, its impact upon biofilm development has not been demonstrated in the rhizosphere, where biofilms influence terrestrial carbon and nitrogen cycles with ramifications for crop and soil health. Furthermore, the relationships between soil moisture and the rates of PCA biosynthesis and degradation have not been established. In this study, expression of PCA biosynthesis genes was upregulated relative to background transcription, and persistence of PCA was slightly decreased in dryland relative to irrigated wheat rhizospheres. Biofilms in dryland rhizospheres inoculated with the PCA-producing (PCA+) strain Pseudomonas synxantha 2-79RN10 were more robust than those in rhizospheres inoculated with an isogenic PCA-deficient (PCA-) mutant strain. This trend was reversed in irrigated rhizospheres. In dryland PCA+ rhizospheres, the turnover of 15 N-labelled rhizobacterial biomass was slower than in the PCA- and irrigated PCA+ treatments, and incorporation of bacterial 15 N into root cell walls was observed in multiple treatments. These results indicate that PCA promotes biofilm development in dryland rhizospheres, and likely influences crop nutrition and soil health in dryland wheat fields.}, } @article {pmid29687552, year = {2018}, author = {Cerdó, T and Ruiz, A and Acuña, I and Jáuregui, R and Jehmlich, N and Haange, SB and von Bergen, M and Suárez, A and Campoy, C}, title = {Gut microbial functional maturation and succession during human early life.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14235}, pmid = {29687552}, issn = {1462-2920}, abstract = {The evolutional trajectory of gut microbial colonization from birth has been shown to prime for health later in life. Here, we combined cultivation-independent 16S rRNA gene sequencing and metaproteomics to investigate the functional maturation of gut microbiota in faecal samples from full-term healthy infants collected at 6 and 18 months of age. Phylogenetic analysis of the metaproteomes showed that Bifidobacterium provided the highest number of distinct protein groups. Considerable divergences between taxa abundance and protein phylogeny were observed at all taxonomic ranks. Age had a profound effect on early microbiota where compositional and functional diversity of less dissimilar communities increased with time. Comparisons of the relative abundances of proteins revealed the transition of taxon-associated saccharolytic and fermentation strategies from milk and mucin-derived monosaccharide catabolism feeding acetate/propanoate synthesis to complex food-derived hexoses fuelling butanoate production. Furthermore, co-occurrence network analysis uncovered two anti-correlated modules of functional taxa. A low-connected Bifidobacteriaceae-centred guild of facultative anaerobes was succeeded by a rich club of obligate anaerobes densely interconnected around Lachnospiraceae, underpinning their pivotal roles in microbial ecosystem assemblies. Our findings establish a framework to visualize whole microbial community metabolism and ecosystem succession dynamics, proposing opportunities for microbiota-targeted health-promoting strategies early in life.}, } @article {pmid29687546, year = {2018}, author = {Zhang, LM and Duff, AM and Smith, CJ}, title = {Community and functional shifts in ammonia oxidizers across terrestrial and marine (soil/sediment) boundaries in two coastal Bay ecosystems.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2834-2853}, doi = {10.1111/1462-2920.14238}, pmid = {29687546}, issn = {1462-2920}, support = {//Science Foundation Ireland/ ; 11/SIRG/B2159//Marie-Curie Action COFUND/ ; }, abstract = {Terrestrial-marine boundaries are significant sites of biogeochemical activity with delineated gradients from land to sea. While niche differentiation of ammonia-oxidizing archaea (AOA) and bacteria (AOB) driven by pH and nitrogen is well known, the patterns and environmental drivers of AOA and AOB community structure and activity across soil-sediment boundaries have not yet been determined. In this study, nitrification potential rate, community composition and transcriptional activity of AOA and AOB in soil, soil/sediment interface and sediments of two coastal Bays were characterized using a combination of field investigations and microcosm incubations. At DNA level, amoA gene abundances of AOA were significantly greater than AOB in soil, while in sediments AOB were significantly more abundant than AOA, but at the soil/sediment interface there were equal numbers of AOA and AOB amoA genes. Microcosm incubations provided further evidence, through qPCR and DGGE-sequencing analysis of amoA transcripts, that AOA were active in soil, AOB in sediment and both AOA and AOB were active at the soil/sediment interface. The AOA and AOB community composition shifted across the coastal soil-interface-sediment gradient with salinity and pH identified as major environmental drivers.}, } @article {pmid29687545, year = {2018}, author = {Brodersen, KE and Siboni, N and Nielsen, DA and Pernice, M and Ralph, PJ and Seymour, J and Kühl, M}, title = {Seagrass rhizosphere microenvironment alters plant-associated microbial community composition.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2854-2864}, doi = {10.1111/1462-2920.14245}, pmid = {29687545}, issn = {1462-2920}, support = {LP110200454//Australian Research Council/ ; FT130100218//Australian Research Council/ ; CF16-0899//Carlsberg Foundation/ ; //Augustinus Foundation/ ; //P.A. Fiskers Fund/ ; //Sapere-Aude Advanced grant from the Danish Council for Independent Research Natural Sciences/ ; }, abstract = {The seagrass rhizosphere harbors dynamic microenvironments, where plant-driven gradients of O2 and dissolved organic carbon form microhabitats that select for distinct microbial communities. To examine how seagrass-mediated alterations of rhizosphere geochemistry affect microbial communities at the microscale level, we applied 16S rRNA amplicon sequencing of artificial sediments surrounding the meristematic tissues of the seagrass Zostera muelleri together with microsensor measurements of the chemical conditions at the basal leaf meristem (BLM). Radial O2 loss (ROL) from the BLM led to ∼ 300 µm thick oxic microzones, wherein pronounced decreases in H2 S and pH occurred. Significantly higher relative abundances of sulphate-reducing bacteria were observed around the meristematic tissues compared to the bulk sediment, especially around the root apical meristems (RAM; ∼ 57% of sequences). Within oxic microniches, elevated abundances of sulphide-oxidizing bacteria were observed compared to the bulk sediment and around the RAM. However, sulphide oxidisers within the oxic microzone did not enhance sediment detoxification, as rates of H2 S re-oxidation here were similar to those observed in a pre-sterilized root/rhizome environment. Our results provide novel insights into how chemical and microbiological processes in the seagrass rhizosphere modulate plant-microbe interactions potentially affecting seagrass health.}, } @article {pmid29687151, year = {2018}, author = {Moazamian, E and Bahador, N and Azarpira, N and Rasouli, M}, title = {Anti-cancer Parasporin Toxins of New Bacillus thuringiensis Against Human Colon (HCT-116) and Blood (CCRF-CEM) Cancer Cell Lines.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1090-1098}, pmid = {29687151}, issn = {1432-0991}, mesh = {Bacillus thuringiensis/classification/genetics/*metabolism ; Cell Line, Tumor ; DNA, Bacterial/genetics ; Endotoxins/*chemistry/classification/*pharmacology ; Erythrocytes/drug effects ; HCT116 Cells ; Hemolysis/drug effects ; Humans ; Iran ; }, abstract = {Bacillus thuringiensis is one of the most important microorganisms used against cancer cell lines in latest studies all over the world. This study aims to perform the isolation, molecular identification, and to identify novel B. thuringiensis strains that specifically targeting human cancer cell-killing activities in Iran. A total of 88 B. thuringiensis isolates were recovered from Iran. Upon the treatment of the non-hemolytic crystal proteins by proteinase K, five isolates belonging to three biotypes, thuringiensis, kurstaki and sotto of B. thuringiensis are found to have different cytotoxicity toward HCT-116 and CCRF-CEM cell lines. Digested inclusions of the isolates consisted of one major poly peptide of 34-kDa, as estimated by sodium dodecyl-sulfate polyacrylamide gel electrophoresis. The structure, molecular identification, and functionality of five isolates inclusion proteins have shown to be closely like to parasporin-2 but their size of activated protein is not similar to this parasporin. It is unclear that discovered damaging proteins are parasporin-2. This 34-kD protein exhibited varying degrees of cytocidal activity toward human colon and blood cancer cells and caused cell swelling and the formation of blebs in the surface of the cells or alteration in cytoskeleton. The soil in the humid and temperate climates of Iran is a good reservoir for parasporin producing B. thuringiensis. The isolated B. thuringiensis strains exhibit specific and different cytocidal activities against human colon and blood cancer cells. Parasporin is a novel cytotoxic protein to human cancer cells produced by B. thuringiensis and these toxins appeared to attack an identical target on human cancer cells.}, } @article {pmid29687150, year = {2018}, author = {Collins, C and Almuzara, M and Saigo, M and Montaña, S and Chiem, K and Traglia, G and Mussi, MA and Tolmasky, M and Iriarte, A and Vay, C and Ramirez, MS}, title = {Whole-Genome Analysis of an Extensively Drug-Resistance Empedobacter falsenii Strain Reveals Distinct Features and the Presence of a Novel Metallo-ß-Lactamase (EBR-2).}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1084-1089}, pmid = {29687150}, issn = {1432-0991}, support = {2T37MD001368//National Institute on Minority Health and Health Disparities, National Institute of Health/ ; }, mesh = {Amino Acid Sequence ; Ampicillin/metabolism ; Anti-Bacterial Agents/metabolism/pharmacology ; Cefepime ; Cephalosporins/metabolism ; Cross Infection/microbiology ; Drug Resistance, Multiple, Bacterial/*genetics ; *Flavobacteriaceae/drug effects/genetics/metabolism ; Genome, Bacterial/genetics ; Humans ; Meropenem ; Microbial Sensitivity Tests ; Penicillin G/metabolism ; Thienamycins/metabolism ; beta-Lactamases/*genetics ; }, abstract = {The spread of antibiotic resistance is rapidly threatening the effectiveness of antibiotics in the clinical setting. Many infections are being caused by known and unknown pathogenic bacteria that are resistant to many or all antibiotics currently available. Empedobacter falsenii is a nosocomial pathogen that can cause human infections. E. falsenii Wf282 strain was found to be resistant to many antibiotics, including carbapenems and colistin. Whole-genome shotgun sequencing of the strain was performed, and distinct features were identified. A novel metallo-β-lactamase, named EBR-2, was found, suggesting a potential role of E. falsenii as a reservoir of β-lactamases and other resistance determinants also found in its genome. The EBR-2 protein showed the highest catalytic efficiency for penicillin G as compared to meropenem and ampicillin and was unable to hydrolyze cefepime. The results described in this work broaden the current understanding of the role of β-lactamases in the Flavobacteriaceae family and suggest that E. falsenii Wf282 may be a reservoir of these novel resistance determinants.}, } @article {pmid29686858, year = {2018}, author = {Bréchet, LM and Lopez-Sangil, L and George, C and Birkett, AJ and Baxendale, C and Castro Trujillo, B and Sayer, EJ}, title = {Distinct responses of soil respiration to experimental litter manipulation in temperate woodland and tropical forest.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3787-3796}, pmid = {29686858}, issn = {2045-7758}, abstract = {Global change is affecting primary productivity in forests worldwide, and this, in turn, will alter long-term carbon (C) sequestration in wooded ecosystems. On one hand, increased primary productivity, for example, in response to elevated atmospheric carbon dioxide (CO 2), can result in greater inputs of organic matter to the soil, which could increase C sequestration belowground. On other hand, many of the interactions between plants and microorganisms that determine soil C dynamics are poorly characterized, and additional inputs of plant material, such as leaf litter, can result in the mineralization of soil organic matter, and the release of soil C as CO 2 during so-called "priming effects". Until now, very few studies made direct comparison of changes in soil C dynamics in response to altered plant inputs in different wooded ecosystems. We addressed this with a cross-continental study with litter removal and addition treatments in a temperate woodland (Wytham Woods) and lowland tropical forest (Gigante forest) to compare the consequences of increased litterfall on soil respiration in two distinct wooded ecosystems. Mean soil respiration was almost twice as high at Gigante (5.0 μmol CO 2 m-2 s-1) than at Wytham (2.7 μmol CO 2 m-2 s-1) but surprisingly, litter manipulation treatments had a greater and more immediate effect on soil respiration at Wytham. We measured a 30% increase in soil respiration in response to litter addition treatments at Wytham, compared to a 10% increase at Gigante. Importantly, despite higher soil respiration rates at Gigante, priming effects were stronger and more consistent at Wytham. Our results suggest that in situ priming effects in wooded ecosystems track seasonality in litterfall and soil respiration but the amount of soil C released by priming is not proportional to rates of soil respiration. Instead, priming effects may be promoted by larger inputs of organic matter combined with slower turnover rates.}, } @article {pmid29686857, year = {2018}, author = {de Boer, TE and Roelofs, D and Vooijs, R and Holmstrup, M and Amorim, MJB}, title = {Population-specific transcriptional differences associated with freeze tolerance in a terrestrial worm.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3774-3786}, pmid = {29686857}, issn = {2045-7758}, abstract = {Enchytraeus albidus is a terrestrial earthworm widespread along the coasts of northern Europe and the Arctic. This species tolerates freezing of body fluids and survives winters in a frozen state. Their acclimatory physiological mechanisms behind freeze tolerance involve increased fluidity of membrane lipids during cold exposure and accumulation of cryoprotectants (glucose) during the freezing process. Gene regulatory processes of these physiological responses have not been studied, partly because no gene expression tools were developed. The main aim of this study was to understand whether the freeze tolerance mechanisms have a transcriptomic basis in E. albidus. For that purpose, first the transcriptome of E. albidus was assembled with RNAseq data. Second, two strains from contrasting thermal environments (Germany and Greenland) were compared by mapping barcoded RNAseq data onto the assembled transcriptome. Both of these strains are freeze tolerant, but Greenland is extremely freeze tolerant. Results showed more plastic responses in the Greenland strain as well as higher constitutive expression of particular stress response genes. These altered transcriptional networks are associated with an adapted homeostasis coping with prolonged freezing conditions in Greenland animals. Previously identified physiological alterations in freeze-tolerant strains of E. albidus are underpinned at the transcriptome level. These processes involve anion transport in the hemolymph, fatty acid metabolism, metabolism, and transport of cryoprotective sugars as well as protection against oxidative stress. Pathway analysis supported most of these processes, and identified additional differentially expressed pathways such as peroxisome and Toll-like receptor signaling. We propose that the freeze-tolerant phenotype is the consequence of genetic adaptation to cold stress and may have driven evolutionary divergence of the two strains.}, } @article {pmid29686856, year = {2018}, author = {Dang, W and Lu, H and Wu, Q and Gao, Y and Qi, Q and Fan, H}, title = {Comparative transcriptional profiling analysis of the effect of heat waves during embryo incubation on the hatchlings of the Chinese soft-shelled turtle (Pelodiscus sinensis).}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3763-3773}, pmid = {29686856}, issn = {2045-7758}, abstract = {Temperature is one of most the important environmental factors that affect the ontogenesis of organisms. In this study, we incubated Chinese soft-shelled turtle eggs at 28°C (control temperature, C treatment), a temperature with a 16°C cold shock and a 36°C heat shock twice per week (S treatment) or a ramp-programmed temperature of 29 ± 9°C (with 12 hr (+) and 12 hr (-) every day) (F treatment). The incubation period, hatching success, hatchling weight, and locomotor performance were significantly different between the controls and the different heat treatment groups. The pathogen challenge results illustrated that hatchlings from the S treatment group were more resistant to bacterial infection, whereas hatchlings from the F treatment group were more vulnerable. We used RNA-seq quantification analysis to identify differentially expressed genes (DEGs) of hatchlings in the S treatment group. Based on the functional annotation results for the DEGs, 9 genes were chosen to verify the RNA-seq results. The background expression of DEGs was also analyzed for the three treatments, as was the regulation of the pathogen challenge. The results showed that 8 DEGs were related to the immune response after pathogen challenge and that temperature was an important factor in differential regulation of the immunity pathways.}, } @article {pmid29686855, year = {2018}, author = {Hume, JB and Wagner, M}, title = {A death in the family: Sea lamprey (Petromyzon marinus) avoidance of confamilial alarm cues diminishes with phylogenetic distance.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3751-3762}, pmid = {29686855}, issn = {2045-7758}, abstract = {Alarm signals released after predator attack function as reliable public information revealing areas of high risk. The utility of this information can extend beyond species boundaries, benefiting heterospecifics capable of recognizing and responding appropriately to the signal. Nonmutually exclusive hypotheses explaining the acquisition of heterospecific reactivity to cues suggest it could be conserved phylogenetically following its evolution in a common ancestor (a species-level effect) and/or learned during periods of shared risk (a population-level effect; e.g., shared predators). Using a laboratory-based space-use behavioral assay, we tested the response of sea lamprey (Petromyzon marinus) to the damage-released alarm cues of five confamilial (sympatric and allopatric) species and two distantly related out-groups: a sympatric teleost (white sucker Catostomus commersonii) and an allopatric agnathan (Atlantic hagfish Myxine glutinosa). We found that sea lamprey differed in their response to conspecific and heterospecific odors; exhibiting progressively weaker avoidance of cues derived from more phylogenetically distant confamilials regardless of current overlap in distribution. Odors from out-groups elicited no response. These findings suggest that a damage-released alarm cue is at least partially conserved within the Petromyzontidae and that sea lamprey perceives predator attacks directed to closely related taxa. These findings are consistent with similar observations from gastropod, amphibian and bony fish taxa, and we discuss this in an eco-evo context to provide a plausible explanation for the acquisition and maintenance of the response in sea lamprey.}, } @article {pmid29686854, year = {2018}, author = {Salvarina, I and Gravier, D and Rothhaupt, KO}, title = {Seasonal bat activity related to insect emergence at three temperate lakes.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3738-3750}, pmid = {29686854}, issn = {2045-7758}, abstract = {Knowledge of aquatic food resources entering terrestrial systems is important for food web studies and conservation planning. Bats, among other terrestrial consumers, often profit from aquatic insect emergence and their activity might be closely related to such events. However, there is a lack of studies which monitor bat activity simultaneously with aquatic insect emergence, especially from lakes. Thus, our aim was to understand the relationship between insect emergence and bat activity, and investigate whether there is a general spatial or seasonal pattern at lakeshores. We assessed whole-night bat activity using acoustic monitoring and caught emerging and aerial flying insects at three different lakes through three seasons. We predicted that insect availability and seasonality explain the variation in bat activity, independent of the lake size and characteristics. Spatial (between lakes) differences of bat activity were stronger than temporal (seasonal) differences. Bat activity did not always correlate to insect emergence, probably because other factors, such as habitat characteristics, or bats' energy requirements, play an important role as well. Aerial flying insects explained bat activity better than the emerged aquatic insects in the lake with lowest insect emergence. Bats were active throughout the night with some activity peaks, and the pattern of their activity also differed among lakes and seasons. Lakes are important habitats for bats, as they support diverse bat communities and activity throughout the night and the year when bats are active. Our study highlights that there are spatial and temporal differences in bat activity and its hourly nocturnal pattern, that should be considered when investigating aquatic-terrestrial interactions or designing conservation and monitoring plans.}, } @article {pmid29686853, year = {2018}, author = {Woolbright, SA and Rehill, BJ and Lindroth, RL and DiFazio, SP and Martinsen, GD and Zinkgraf, MS and Allan, GJ and Keim, P and Whitham, TG}, title = {Large effect quantitative trait loci for salicinoid phenolic glycosides in Populus: Implications for gene discovery.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3726-3737}, pmid = {29686853}, issn = {2045-7758}, abstract = {Genomic studies have been used to identify genes underlying many important plant secondary metabolic pathways. However, genes for salicinoid phenolic glycosides (SPGs)-ecologically important compounds with significant commercial, cultural, and medicinal applications-remain largely undescribed. We used a linkage map derived from a full-sib population of hybrid cottonwoods (Populus spp.) to search for quantitative trait loci (QTL) for the SPGs salicortin and HCH-salicortin. SSR markers and primer sequences were used to anchor the map to the V3.0 P. trichocarpa genome. We discovered 21 QTL for the two traits, including a major QTL for HCH-salicortin (R2 = .52) that colocated with a QTL for salicortin on chr12. Using the V3.0 Populus genome sequence, we identified 2,983 annotated genes and 1,480 genes of unknown function within our QTL intervals. We note ten candidate genes of interest, including a BAHD-type acyltransferase that has been potentially linked to Populus SPGs. Our results complement other recent studies in Populus with implications for gene discovery and the evolution of defensive chemistry in a model genus. To our knowledge, this is the first study to use a full-sib mapping population to identify QTL intervals and gene lists associated with SPGs.}, } @article {pmid29686852, year = {2018}, author = {Schedlbauer, JL and Fetcher, N and Hood, K and Moody, ML and Tang, J}, title = {Effect of growth temperature on photosynthetic capacity and respiration in three ecotypes of Eriophorum vaginatum.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3711-3725}, pmid = {29686852}, issn = {2045-7758}, abstract = {Ecotypic differentiation in the tussock-forming sedge Eriophorum vaginatum has led to the development of populations that are locally adapted to climate in Alaska's moist tussock tundra. As a foundation species, E. vaginatum plays a central role in providing topographic and microclimatic variation essential to these ecosystems, but a changing climate could diminish the importance of this species. As Arctic temperatures have increased, there is evidence of adaptational lag in E. vaginatum, as locally adapted ecotypes now exhibit reduced population growth rates. Whether there is a physiological underpinning to adaptational lag is unknown. Accordingly, this possibility was investigated in reciprocal transplant gardens. Tussocks of E. vaginatum from sites separated by ~1° latitude (Coldfoot: 67°15'N, Toolik Lake: 68°37', Sagwon: 69°25') were transplanted into the Toolik Lake and Sagwon sites and exposed to either an ambient or an experimental warming treatment. Five tussocks pertreatment combination were measured at each garden to determine photosynthetic capacity (i.e., Vcmax and Jmax) and dark respiration rate (Rd) at measurement temperatures of 15, 20, and 25°C. Photosynthetic enhancements or homeostasis were observed for all ecotypes at both gardens under increased growth temperature, indicating no negative effect of elevated temperature on photosynthetic capacity. Further, no evidence of thermal acclimation in Rd was observed for any ecotype, and there was little evidence of ecotypic variation in Rd. As such, no physiological contribution to adaptational lag was observed given the increase in growth temperature (up to ~2°C) provided by this study. Despite neutral to positive effects of increased growth temperature on photosynthesis in E. vaginatum, it appears to confer no lasting advantage to the species.}, } @article {pmid29686851, year = {2018}, author = {Fujita, T and Yamashina, C}, title = {Do consumer-mediated negative effects on plant establishment outweigh the positive effects of a nurse plant?.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3702-3710}, pmid = {29686851}, issn = {2045-7758}, abstract = {Many studies demonstrated the importance of facilitative effect by nurse plant on seedling establishment. Few studies evaluated the negative effects of consumers on plant establishment under nurse plants by dealing with them during multiple demographic processes. We investigated the balance between the facilitative effect and negative effects of consumers during multiple demographic processes in Malawi in southeastern Africa. We chose Ficus natalensis as a nurse plant and compared it with three other microsites in tropical woodlands: Brachystegia floribunda (a dominant woodland species), Uapaca kirkiana (a woodland species), and a treeless site. We quantified the seed rain, postdispersal seed predation, germination, and seedling survival of Syzygium guineense ssp. afromontanum (a common forest species). Within each microsite, we quantified the overall probability of recruitment. We also measured seedling abundance of S. guineense ssp. afromontanum. We found that Ficus natalensis exerted both positive and negative impacts on the establishment of S. guineense ssp. afromontanum. Ficus natalensis facilitated seed deposition, seed germination, and seedling survival. On the other hand, seed removal at postdispersal stage was highest under F. natalensis. Interestingly, B. floribunda also had positive effects on germination and seedling survival, but not on seed deposition. When we excluded the seed arrival stage from our estimation of the recruitment probability, the highest value was found under B. floribunda, not under F. natalensis. When we included the seed arrival stage, however, the order of recruitment probability between F. natalensis and B. floribunda was reversed. The probability was one order of magnitude higher under F. natalensis than under B. floribunda. Our estimation of the probability which included the seed arrival stage was consistent with natural patterns of S. guineense ssp. afromontanum establishment. Despite the presence of opposite effects, the net effects of F. natalensis on S. guineense ssp. afromontanum recruitment in tropical woodlands can be positive.}, } @article {pmid29686850, year = {2018}, author = {Khwaja, N and Preston, SAJ and Briskie, JV and Hatchwell, BJ}, title = {Testing the predictions of sex allocation hypotheses in dimorphic, cooperatively breeding riflemen.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3693-3701}, pmid = {29686850}, issn = {2045-7758}, abstract = {Evolutionary theory predicts that parents should invest equally in the two sexes. If one sex is more costly, a production bias is predicted in favour of the other. Two well-studied causes of differential costs are size dimorphism, in which the larger sex should be more costly, and sex-biased helping in cooperative breeders, in which the more helpful sex should be less costly because future helping "repays" some of its parents' investment. We studied a bird species in which both processes should favor production of males. Female riflemen Acanthisitta chloris are larger than males, and we documented greater provisioning effort in more female-biased broods indicating they are likely costlier to raise. Riflemen are also cooperative breeders, and males provide more help than females. Contrary to expectations, we observed no male bias in brood sex ratios, which did not differ significantly from parity. We tested whether the lack of a population-wide pattern was a result of facultative sex allocation by individual females, but this hypothesis was not supported either. Our results show an absence of adaptive patterns despite a clear directional hypothesis derived from theory. This appears to be associated with a suboptimal female-biased investment ratio. We conclude that predictions of adaptive sex allocation may falter because of mechanistic constraint, unrecognized costs and benefits, or weak selection.}, } @article {pmid29686849, year = {2018}, author = {Lyu, N and Servedio, MR and Sun, YH}, title = {Nonadaptive female pursuit of extrapair copulations can evolve through hitchhiking.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3685-3692}, pmid = {29686849}, issn = {2045-7758}, abstract = {Mounting evidence has indicated that engaging in extrapair copulations (EPCs) might be maladaptive or detrimental to females. It is unclear why such nonadaptive female behavior evolves. In this study, we test two hypotheses about the evolution of female EPC behavior using population genetic models. First, we find that both male preference for allocating extra effort to seek EPCs and female pursuit behavior without costs can be maintained and remain polymorphic in a population via frequency-dependent selection. However, both behaviors cannot evolve when females with pursuit behavior suffer from a decline in male parental care. Second, we present another novel way in which female pursuit behavior can evolve; indirect selection can act on this behavior through a ratchet-like mechanism involving oscillating linkage disequilibria between the target EPC pursuit locus and two other loci determining male mate choice and a female sexual signal. Although the overall positive force of such indirect selection is relatively weak, our results suggest that it may still play a role in promoting the evolution of female EPC behavior when this behavior is nonadaptive (i.e., it is neutral) or only somewhat maladaptive (e.g., males only occasionally lower parental care when their mates pursue EPCs).}, } @article {pmid29686848, year = {2018}, author = {Shi, J and Joshi, J and Tielbörger, K and Verhoeven, KJF and Macel, M}, title = {Costs and benefits of admixture between foreign genotypes and local populations in the field.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3675-3684}, pmid = {29686848}, issn = {2045-7758}, abstract = {Admixture is the hybridization between populations within one species. It can increase plant fitness and population viability by alleviating inbreeding depression and increasing genetic diversity. However, populations are often adapted to their local environments and admixture with distant populations could break down local adaptation by diluting the locally adapted genomes. Thus, admixed genotypes might be selected against and be outcompeted by locally adapted genotypes in the local environments. To investigate the costs and benefits of admixture, we compared the performance of admixed and within-population F1 and F2 generations of the European plant Lythrum salicaria in a reciprocal transplant experiment at three European field sites over a 2-year period. Despite strong differences between site and plant populations for most of the measured traits, including herbivory, we found limited evidence for local adaptation. The effects of admixture depended on experimental site and plant population, and were positive for some traits. Plant growth and fruit production of some populations increased in admixed offspring and this was strongest with larger parental distances. These effects were only detected in two of our three sites. Our results show that, in the absence of local adaptation, admixture may boost plant performance, and that this is particularly apparent in stressful environments. We suggest that admixture between foreign and local genotypes can potentially be considered in nature conservation to restore populations and/or increase population viability, especially in small inbred or maladapted populations.}, } @article {pmid29686847, year = {2018}, author = {Tarroux, A and Lydersen, C and Trathan, PN and Kovacs, KM}, title = {Temporal variation in trophic relationships among three congeneric penguin species breeding in sympatry.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3660-3674}, pmid = {29686847}, issn = {2045-7758}, abstract = {Penguins are a monophyletic group in which many species are found breeding sympatrically, raising questions regarding how these species coexist successfully. Here, the isotopic niche of three sympatric pygoscelid penguin species was investigated at Powell Island, South Orkney Islands, during two breeding seasons (austral summers 2013-2014 and 2015-2016). Measurements of carbon (δ13C) and nitrogen (δ15N) stable isotope ratios were obtained from blood (adults) or feather (chicks) samples collected from Adélie Pygoscelis adeliae, chinstrap P. antarctica, and gentoo P. papua penguins. Isotopic niche regions (a proxy for the realized trophic niches) were computed to provide estimates of the trophic niche width of the studied species during the breeding season. The isotopic niche regions of adults of all three species were similar, but gentoo chicks had noticeably wider isotopic niches than the chicks of the other two species. Moderate to strong overlap in isotopic niche among species was found during each breeding season and for both age groups, suggesting that the potential for competition for shared food sources was similar during the two study years, although the actual level of competition could not be determined owing to the lack of data on resource abundance. Clear interannual shifts in isotopic niche were seen in all three species, though of lower amplitude for adult chinstrap penguins. These shifts were due to variation in carbon, but not nitrogen, isotopic ratios, which could indicate either a change in isotopic signature of their prey or a switch to an alternative food web. The main conclusions of this study are that (1) there is a partial overlap in the isotopic niches of these three congeneric species and that (2) they responded similarly to changes that likely occurred at the base of their food chain between the 2 years of the study.}, } @article {pmid29686846, year = {2018}, author = {You, X and Liu, J}, title = {Modeling the spatial and temporal dynamics of riparian vegetation induced by river flow fluctuation.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3648-3659}, pmid = {29686846}, issn = {2045-7758}, abstract = {River flow fluctuation has an important influence on riparian vegetation dynamics. A temporally segmented stochastic model focusing on a same-aged population is developed for the purpose of describing both spatial and temporal dynamics of riparian vegetation. In the model, the growth rate of population, rather than carrying capacity, is modeled as the random variable. This model has explicit physical meaning. The model deduces a process-based solution. From the solution process, the probability density of spatial distribution can be derived; therefore, the spatial distribution of population abundance can be described. The lifespan of a same-aged population and the age structure of the species-specific population can also be studied with the aid of this temporally segmented model. The influence of correlation time of river flow fluctuation is also quantified according to the model. The calibration of model parameters and model application are discussed. The model provides a computer-aided method to simulate and predict vegetation dynamics during river flow disturbances. Meanwhile, the model is open and allows for more accurate and concrete modeling of growth rate. Because of the Markov property involved in the process-based solution, the model also has the ability to deal with cases of nonstationary disturbances.}, } @article {pmid29686845, year = {2018}, author = {Yuan, L and Wilder, S and Raubenheimer, D and Simpson, SJ and Shaw, M and McAllan, BM}, title = {Dietary protein supplementation and its consequences for intake, digestion, and physical activity of a carnivorous marsupial, Sminthopsis crassicaudata.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3636-3647}, pmid = {29686845}, issn = {2045-7758}, abstract = {Diet regulation behavior can mediate the consequences of imbalanced diets for animal well-being, particularly for captive species that have little dietary choice. Dasyurids (carnivorous marsupials) are of conservation concern in Australia, and many species are in captive breeding programmes. However, their nutrient targets and dietary regulation behaviors are poorly understood, a limitation that may decrease the breeding success and well-being of captive animals. We tested how dietary protein content influenced the intake and utilization of nutrients, physical activity, and body mass of fat-tailed dunnarts Sminthopsis crassicaudata. Twelve adult dunnarts from six sibling pairs (one female and one male per pair) were provided ad libitum access to three diets in a repeated measures design: cat food, cat food supplemented with raw lean beef (1:1), and cat food supplemented with cooked lean beef (1:1). Food intake, activity level, and fecal output were measured daily. Dunnarts significantly decreased food intake, increased protein digestion, and physical activity, but body mass was unchanged when on the high-protein diet compared to the normal cat food diet. These observations suggest a capacity of dunnarts to maintain constant body mass using a dynamic balance of feeding, digestion, and activity. We also found a significant effect of family, with differences between families as large as the difference between the diet treatments, suggesting a genetic component to diet selection. The nutrient regulation responses of dunnarts to high-protein diets and the strong family effects provide important messages for the management of populations of small carnivores, including the aspects of dietary manipulation and conservation of genetic diversity.}, } @article {pmid29686844, year = {2018}, author = {Fisher, MA and Vinson, JE and Gittleman, JL and Drake, JM}, title = {The description and number of undiscovered mammal species.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3628-3635}, pmid = {29686844}, issn = {2045-7758}, abstract = {Global species counts are a key measure of biodiversity and associated metrics of conservation. It is both scientifically and practically important to know how many species exist, how many undescribed species remain, and where they are found. We modify a model for the number of undescribed species using species description data and incorporating taxonomic information. We assume a Poisson distribution for the number of species described in an interval and use maximum likelihood to estimate parameter values of an unknown intensity function. To test the model's performance, we performed a simulation study comparing our method to a previous model under conditions qualitatively similar to those related to mammal species description over the last two centuries. Because our model more accurately estimates the total number of species, we predict that 5% of mammals remain undescribed. We applied our model to determine the biogeographic realms which hold these undescribed species.}, } @article {pmid29686843, year = {2018}, author = {Almeida, SM and Juen, L and Sobral, FL and Santos, MPD}, title = {The influence of biogeographic history on the functional and phylogenetic diversity of passerine birds in savannas and forests of the Brazilian Amazon.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3617-3627}, pmid = {29686843}, issn = {2045-7758}, abstract = {Passeriformes is the largest and most diverse avian order in the world and comprises the Passeri and Tyranni suborders. These suborders constitute a monophyletic group, but differ in their ecology and history of occupation of South America. We investigated the influence of biogeographic history on functional and phylogenetic diversities of Passeri and Tyranni in forest and savanna habitats in the Brazilian Amazon. We compiled species composition data for 34 Passeriformes assemblages, 12 in savannas and 22 in forests. We calculated the functional (Rao's quadratic entropy, FD Q) and phylogenetic diversities (mean pairwise distance, MPD, and mean nearest taxon distance, MNTD), and the functional beta diversity to investigate the potential role of biogeographic history in shaping ecological traits and species lineages of both suborders. The functional diversity of Passeri was higher than for Tyranni in both habitats. The MPD for Tyranni was higher than for Passeri in forests; however, there was no difference between the suborders in savannas. In savannas, Passeri presented higher MNTD than Tyranni, while in forest areas, Tyranni assemblages showed higher MNTD than Passeri. We found a high functional turnover (~75%) between Passeri and Tyranni in both habitats. The high functional diversity of Passeri in both habitats is due to the high diversity of ecological traits exhibited by species of this group, which enables the exploitation of a wide variety of resources and foraging strategies. The higher Tyranni MPD and MNTD in forests is likely due to Tyranni being older settlers in this habitat, resulting in the emergence and persistence of more lineages. The higher Passeri MNTD in savannas can be explained by the existence of a larger number of different Passeri lineages adapted to this severe habitat. The high functional turnover between the suborders in both habitats suggests an ecological strategy to avoid niche overlap.}, } @article {pmid29686842, year = {2018}, author = {Dornburg, A and Warren, DL and Zapfe, KL and Morris, R and Iglesias, TL and Lamb, A and Hogue, G and Lukas, L and Wong, R}, title = {Testing ontogenetic patterns of sexual size dimorphism against expectations of the expensive tissue hypothesis, an intraspecific example using oyster toadfish (Opsanus tau).}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3609-3616}, pmid = {29686842}, issn = {2045-7758}, abstract = {Trade-offs associated with sexual size dimorphism (SSD) are well documented across the Tree of Life. However, studies of SSD often do not consider potential investment trade-offs between metabolically expensive structures under sexual selection and other morphological modules. Based on the expectations of the expensive tissue hypothesis, investment in one metabolically expensive structure should come at the direct cost of investment in another. Here, we examine allometric trends in the ontogeny of oyster toadfish (Opsanus tau) to test whether investment in structures known to have been influenced by strong sexual selection conform to these expectations. Despite recovering clear changes in the ontogeny of a sexually selected trait between males and females, we find no evidence for predicted ontogenetic trade-offs with metabolically expensive organs. Our results are part of a growing body of work demonstrating that increased investment in one structure does not necessarily drive a wholesale loss of mass in one or more organs.}, } @article {pmid29686841, year = {2018}, author = {Ju, MM and Fu, Y and Zhao, GF and He, CZ and Li, ZH and Tian, B}, title = {Effects of the Tanaka Line on the genetic structure of Bombax ceiba (Malvaceae) in dry-hot valley areas of southwest China.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3599-3608}, pmid = {29686841}, issn = {2045-7758}, abstract = {Southwest China is an important biodiversity hotspot. The interactions among the complex topography, climate change, and ecological factors in the dry-hot valley areas in southwest China may have profoundly affected the genetic structure of plant species in this region. In this study, we determined the effects of the Tanaka Line on genetic variation in the wild Bombax ceiba tree in southwest China. We sampled 224 individuals from 17 populations throughout the dry-hot valley regions. Six polymorphic expressed sequence tag-simple sequence repeat primers were employed to sequence the PCR products using the first-generation Sanger technique. The analysis based on population genetics suggested that B. ceiba exhibited a high level of gene diversity (HE: 0.2377-0.4775; I: 0.3997-0.7848). The 17 populations were divided into two groups by cluster analysis, which corresponded to geographic characters on each side of the Tanaka Line. In addition, a Mantel test indicated that the phylogeographic structure among the populations could be fitted to the isolation-by-distance model (r2 = .2553, p < .001). A barrier test indicated that there were obstacles among populations and between the two groups due to complex terrain isolation and geographic heterogeneity. We inferred that the Tanaka Line might have promoted the intraspecific phylogeographic subdivision and divergence of B. ceiba. These results provide new insights into the effects of the Tanaka Line on genetic isolation and population differentiation of plant species in southwest China.}, } @article {pmid29686840, year = {2018}, author = {Wang, Y and Lai, L and Du, H and Jiang, L and Wang, F and Zhang, C and Zhuang, P and Zheng, Y}, title = {Phylogeny, habitat together with biological and ecological factors can influence germination of 36 subalpine Rhododendron species from the eastern Tibetan Plateau.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3589-3598}, pmid = {29686840}, issn = {2045-7758}, abstract = {The reproductive stages of the life cycle are crucial in explaining the distribution patterns of plant species because of their extreme vulnerability to environmental conditions. Despite reported evidence that seed germination is related to habitat macroclimatic characteristics, such as mean annual temperature, the effect of this trait in controlling plant species distribution has not yet been systematically and quantitatively evaluated. To learn whether seed germination can predict species distribution along altitude gradients, we examined germination data of 36 Rhododendron species in southeastern Tibet originating from contrasting altitudes, habitats, plant heights, seed masses, and phylogenies. Germination varied significantly with altitude, habitat, plant height, and phylogeny and was higher in the light than in the dark. Germination percentage was highest at 10:20°C in the light and 15:25°C in the dark. As altitude increased, germination percentages first rose and then decreased, being highest at 3,500-4,000 m. Germination percentage and rate were highest on rocky slopes, increasing as seed mass and plant height rose. Variations in germination percentage and rate were not significant at subgenera, section, and subsection levels, but they were significant at species level. The results suggested that the relationship between germination and altitude may provide insights into species distribution patterns. Further, germination patterns are a result of long-term evolution as well as taxonomic constraints.}, } @article {pmid29686839, year = {2018}, author = {Rorick, MM and Artzy-Randrup, Y and Ruybal-Pesántez, S and Tiedje, KE and Rask, TS and Oduro, A and Ghansah, A and Koram, K and Day, KP and Pascual, M}, title = {Signatures of competition and strain structure within the major blood-stage antigen of Plasmodium falciparum in a local community in Ghana.}, journal = {Ecology and evolution}, volume = {8}, number = {7}, pages = {3574-3588}, pmid = {29686839}, issn = {2045-7758}, support = {R01 TW009670/TW/FIC NIH HHS/United States ; }, abstract = {The concept of niche partitioning has received considerable theoretical attention at the interface of ecology and evolution of infectious diseases. Strain theory postulates that pathogen populations can be structured into distinct nonoverlapping strains by frequency-dependent selection in response to intraspecific competition for host immune space. The malaria parasite Plasmodium falciparum presents an opportunity to investigate this phenomenon in nature, under conditions of high recombination rate and extensive antigenic diversity. The parasite's major blood-stage antigen, Pf EMP1, is encoded by the hyperdiverse var genes. With a dataset that includes thousands of var DBLα sequence types sampled from asymptomatic cases within an area of high endemicity in Ghana, we address how var diversity is distributed within isolates and compare this to the distribution of microsatellite allelic diversity within isolates to test whether antigenic and neutral regions of the genome are structured differently. With respect to var DBLα sequence types, we find that on average isolates exhibit significantly lower overlap than expected randomly, but that there also exists frequent pairs of isolates that are highly related. Furthermore, the linkage network of var DBLα sequence types reveals a pattern of nonrandom modularity unique to these antigenic genes, and we find that modules of highly linked DBLα types are not explainable by neutral forces related to var recombination constraints, microsatellite diversity, sampling location, host age, or multiplicity of infection. These findings of reduced overlap and modularity among the var antigenic genes are consistent with a role for immune selection as proposed by strain theory. Identifying the evolutionary and ecological dynamics that are responsible for the nonrandom structure in P. falciparum antigenic diversity is important for designing effective intervention in endemic areas.}, } @article {pmid29686747, year = {2018}, author = {Mateos-Rivera, A and Islam, T and Marshall, IPG and Schreiber, L and Øvreås, L}, title = {High-quality draft genome of the methanotroph Methylovulum psychrotolerans Str. HV10-M2 isolated from plant material at a high-altitude environment.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {10}, pmid = {29686747}, issn = {1944-3277}, support = {294200//European Research Council/International ; }, abstract = {Here we present the genome of Methylovulum psychrotolerans strain HV10-M2, a methanotroph isolated from Hardangervidda national park (Norway). This strain represents the second of the two validly published species genus with a sequenced genome. The other is M. miyakonense HT12, which is the type strain of the species and the type species of the genus Methylovulum. We present the genome of M. psychrotolerants str. HV10-M2 and discuss the differences between M. psychrotolerans and M. miyakonense. The genome size of M. psychrotolerans str. HV10-M2 is 4,923,400 bp and contains 4415 protein-coding genes, 50 RNA genes and an average GC content of 50.88%.}, } @article {pmid29686433, year = {2018}, author = {Gaston, KJ and Cox, DTC and Canavelli, SB and García, D and Hughes, B and Maas, B and Martínez, D and Ogada, D and Inger, R}, title = {Population Abundance and Ecosystem Service Provision: The Case of Birds.}, journal = {Bioscience}, volume = {68}, number = {4}, pages = {264-272}, pmid = {29686433}, issn = {0006-3568}, abstract = {Although there is a diversity of concerns about recent persistent declines in the abundances of many species, the implications for the associated delivery of ecosystem services to people are surprisingly poorly understood. In principle, there are a broad range of potential functional relationships between the abundance of a species or group of species and the magnitude of ecosystem-service provision. Here, we identify the forms these relationships are most likely to take. Focusing on the case of birds, we review the empirical evidence for these functional relationships, with examples of supporting, regulating, and cultural services. Positive relationships between abundance and ecosystem-service provision are the norm (although seldom linear), we found no evidence for hump-shaped relationships, and negative ones were limited to cultural services that value rarity. Given the magnitude of abundance declines among many previously common species, it is likely that there have been substantial losses of ecosystem services, providing important implications for the identification of potential tipping points in relation to defaunation resilience, biodiversity conservation, and human well-being.}, } @article {pmid29686415, year = {2018}, author = {Gesmundo, NJ and Sauvagnat, B and Curran, PJ and Richards, MP and Andrews, CL and Dandliker, PJ and Cernak, T}, title = {Nanoscale synthesis and affinity ranking.}, journal = {Nature}, volume = {557}, number = {7704}, pages = {228-232}, doi = {10.1038/s41586-018-0056-8}, pmid = {29686415}, issn = {1476-4687}, mesh = {Biological Assay ; Catalysis ; Checkpoint Kinase 1/antagonists & inhibitors/chemistry ; Drug Evaluation, Preclinical ; Kinetics ; Ligands ; Mass Spectrometry ; Mitogen-Activated Protein Kinase 1/antagonists & inhibitors/chemistry ; Nanotechnology/*methods ; Protein Kinase Inhibitors/*chemical synthesis/*chemistry/pharmacology ; Protein-Serine-Threonine Kinases/antagonists & inhibitors/chemistry ; Proteins/antagonists & inhibitors/*chemistry ; Substrate Specificity ; }, abstract = {Most drugs are developed through iterative rounds of chemical synthesis and biochemical testing to optimize the affinity of a particular compound for a protein target of therapeutic interest. This process is challenging because candidate molecules must be selected from a chemical space of more than 1060 drug-like possibilities 1 , and a single reaction used to synthesize each molecule has more than 107 plausible permutations of catalysts, ligands, additives and other parameters 2 . The merger of a method for high-throughput chemical synthesis with a biochemical assay would facilitate the exploration of this enormous search space and streamline the hunt for new drugs and chemical probes. Miniaturized high-throughput chemical synthesis3-7 has enabled rapid evaluation of reaction space, but so far the merger of such syntheses with bioassays has been achieved with only low-density reaction arrays, which analyse only a handful of analogues prepared under a single reaction condition8-13. High-density chemical synthesis approaches that have been coupled to bioassays, including on-bead 14 , on-surface 15 , on-DNA 16 and mass-encoding technologies 17 , greatly reduce material requirements, but they require the covalent linkage of substrates to a potentially reactive support, must be performed under high dilution and must operate in a mixture format. These reaction attributes limit the application of transition-metal catalysts, which are easily poisoned by the many functional groups present in a complex mixture, and of transformations for which the kinetics require a high concentration of reactant. Here we couple high-throughput nanomole-scale synthesis with a label-free affinity-selection mass spectrometry bioassay. Each reaction is performed at a 0.1-molar concentration in a discrete well to enable transition-metal catalysis while consuming less than 0.05 milligrams of substrate per reaction. The affinity-selection mass spectrometry bioassay is then used to rank the affinity of the reaction products to target proteins, removing the need for time-intensive reaction purification. This method enables the primary synthesis and testing steps that are critical to the invention of protein inhibitors to be performed rapidly and with minimal consumption of starting materials.}, } @article {pmid29686399, year = {2018}, author = {Cloney, R}, title = {Linking tissues to disease.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {328}, doi = {10.1038/s41576-018-0009-y}, pmid = {29686399}, issn = {1471-0064}, } @article {pmid29686398, year = {2018}, author = {Koch, L}, title = {Taking aim at transcriptional regulator targets.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {328}, doi = {10.1038/s41576-018-0010-5}, pmid = {29686398}, issn = {1471-0064}, } @article {pmid29686388, year = {2018}, author = {deCarvalho, AC and Kim, H and Poisson, LM and Winn, ME and Mueller, C and Cherba, D and Koeman, J and Seth, S and Protopopov, A and Felicella, M and Zheng, S and Multani, A and Jiang, Y and Zhang, J and Nam, DH and Petricoin, EF and Chin, L and Mikkelsen, T and Verhaak, RGW}, title = {Discordant inheritance of chromosomal and extrachromosomal DNA elements contributes to dynamic disease evolution in glioblastoma.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {708-717}, pmid = {29686388}, issn = {1546-1718}, support = {P30 CA034196/CA/NCI NIH HHS/United States ; R01 CA190121/CA/NCI NIH HHS/United States ; }, abstract = {To understand how genomic heterogeneity of glioblastoma (GBM) contributes to poor therapy response, we performed DNA and RNA sequencing on GBM samples and the neurospheres and orthotopic xenograft models derived from them. We used the resulting dataset to show that somatic driver alterations including single-nucleotide variants, focal DNA alterations and oncogene amplification on extrachromosomal DNA (ecDNA) elements were in majority propagated from tumor to model systems. In several instances, ecDNAs and chromosomal alterations demonstrated divergent inheritance patterns and clonal selection dynamics during cell culture and xenografting. We infer that ecDNA was unevenly inherited by offspring cells, a characteristic that affects the oncogenic potential of cells with more or fewer ecDNAs. Longitudinal patient tumor profiling found that oncogenic ecDNAs are frequently retained throughout the course of disease. Our analysis shows that extrachromosomal elements allow rapid increase of genomic heterogeneity during GBM evolution, independently of chromosomal DNA alterations.}, } @article {pmid29686387, year = {2018}, author = {Verbanck, M and Chen, CY and Neale, B and Do, R}, title = {Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {693-698}, pmid = {29686387}, issn = {1546-1718}, support = {R01 MH094469/MH/NIMH NIH HHS/United States ; R35 GM124836/GM/NIGMS NIH HHS/United States ; R01 HL139865/HL/NHLBI NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; U01 HG009088/HG/NHGRI NIH HHS/United States ; }, abstract = {Horizontal pleiotropy occurs when the variant has an effect on disease outside of its effect on the exposure in Mendelian randomization (MR). Violation of the 'no horizontal pleiotropy' assumption can cause severe bias in MR. We developed the Mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO) test to identify horizontal pleiotropic outliers in multi-instrument summary-level MR testing. We showed using simulations that the MR-PRESSO test is best suited when horizontal pleiotropy occurs in <50% of instruments. Next we applied the MR-PRESSO test, along with several other MR tests, to complex traits and diseases and found that horizontal pleiotropy (i) was detectable in over 48% of significant causal relationships in MR; (ii) introduced distortions in the causal estimates in MR that ranged on average from -131% to 201%; (iii) induced false-positive causal relationships in up to 10% of relationships; and (iv) could be corrected in some but not all instances.}, } @article {pmid29686386, year = {2018}, author = {York, A}, title = {Treading the same path.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {330-331}, doi = {10.1038/s41579-018-0015-2}, pmid = {29686386}, issn = {1740-1534}, } @article {pmid29686371, year = {2018}, author = {Ponomarenko, A and Korotkova, T}, title = {Hunger is a gatekeeper of pain in the brain.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {445-446}, doi = {10.1038/d41586-018-04759-0}, pmid = {29686371}, issn = {1476-4687}, mesh = {Brain ; Humans ; *Hunger ; *Pain ; }, } @article {pmid29686370, year = {2018}, author = {Heald, R}, title = {A lab co-op helps young faculty members to thrive.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {409}, doi = {10.1038/d41586-018-04923-6}, pmid = {29686370}, issn = {1476-4687}, mesh = {California ; *Cooperative Behavior ; Faculty/*organization & administration/psychology ; Interdisciplinary Research/organization & administration ; Laboratories/*organization & administration ; Motivation ; Research Personnel/*organization & administration/*psychology ; *Social Support ; Workforce ; }, } @article {pmid29686369, year = {2018}, author = {Gee, H}, title = {Shrimp cause a stir.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {440}, doi = {10.1038/d41586-018-04673-5}, pmid = {29686369}, issn = {1476-4687}, } @article {pmid29686368, year = {2018}, author = {Flynn, PM}, title = {A broader look at adolescents with perinatal HIV.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {439-440}, doi = {10.1038/d41586-018-04476-8}, pmid = {29686368}, issn = {1476-4687}, mesh = {Adolescent ; Anti-HIV Agents/*therapeutic use ; Child, Preschool ; Cohort Studies ; HIV Infections/*drug therapy/*epidemiology/mortality/virology ; Humans ; Infant ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*statistics & numerical data ; }, } @article {pmid29686367, year = {2018}, author = {Thompson, EW and Nagaraj, SH}, title = {Transition states that allow cancer to spread.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {442-444}, doi = {10.1038/d41586-018-04403-x}, pmid = {29686367}, issn = {1476-4687}, mesh = {*Epithelial-Mesenchymal Transition ; Humans ; *Neoplasms ; }, } @article {pmid29686366, year = {2018}, author = {Kuo, CJ and Curtis, C}, title = {Organoids reveal cancer dynamics.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {441-442}, doi = {10.1038/d41586-018-03841-x}, pmid = {29686366}, issn = {1476-4687}, mesh = {Humans ; *Neoplasms ; *Organoids ; }, } @article {pmid29686297, year = {2018}, author = {Hryckowian, AJ and Van Treuren, W and Smits, SA and Davis, NM and Gardner, JO and Bouley, DM and Sonnenburg, JL}, title = {Microbiota-accessible carbohydrates suppress Clostridium difficile infection in a murine model.}, journal = {Nature microbiology}, volume = {3}, number = {6}, pages = {662-669}, pmid = {29686297}, issn = {2058-5276}, support = {R01 DK085025/DK/NIDDK NIH HHS/United States ; T32 AI007328/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridium difficile is an opportunistic diarrhoeal pathogen, and C. difficile infection (CDI) represents a major health care concern, causing an estimated 15,000 deaths per year in the United States alone 1 . Several enteric pathogens, including C. difficile, leverage inflammation and the accompanying microbial dysbiosis to thrive in the distal gut 2 . Although diet is among the most powerful available tools for affecting the health of humans and their relationship with their microbiota, investigation into the effects of diet on CDI has been limited. Here, we show in mice that the consumption of microbiota-accessible carbohydrates (MACs) found in dietary plant polysaccharides has a significant effect on CDI. Specifically, using a model of antibiotic-induced CDI that typically resolves within 12 days of infection, we demonstrate that MAC-deficient diets perpetuate CDI. We show that C. difficile burdens are suppressed through the addition of either a diet containing a complex mixture of MACs or a simplified diet containing inulin as the sole MAC source. We show that switches between these dietary conditions are coincident with changes to microbiota membership, its metabolic output and C. difficile-mediated inflammation. Together, our data demonstrate the outgrowth of MAC-utilizing taxa and the associated end products of MAC metabolism, namely, the short-chain fatty acids acetate, propionate and butyrate, are associated with decreased C. difficile fitness despite increased C. difficile toxin expression in the gut. Our findings, when placed into the context of the known fibre deficiencies of a human Western diet, provide rationale for pursuing MAC-centric dietary strategies as an alternate line of investigation for mitigating CDI.}, } @article {pmid29686238, year = {2018}, author = {Li, C and Zhang, J}, title = {Multi-environment fitness landscapes of a tRNA gene.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {1025-1032}, pmid = {29686238}, issn = {2397-334X}, support = {R01 GM103232/GM/NIGMS NIH HHS/United States ; }, abstract = {A fitness landscape (FL) describes the genotype-fitness relationship in a given environment. To explain and predict evolution, it is imperative to measure the FL in multiple environments because the natural environment changes frequently. Using a high-throughput method that combines precise gene replacement with next-generation sequencing, we determine the in vivo FL of a yeast tRNA gene comprising over 23,000 genotypes in four environments. Although genotype-by-environment interaction is abundantly detected, its pattern is so simple that we can transform an existing FL to that in a new environment with fitness measures of only a few genotypes in the new environment. Under each environment, we observe prevalent, negatively biased epistasis between mutations. Epistasis-by-environment interaction is also prevalent, but trends in epistasis difference between environments are predictable. Our study thus reveals simple rules underlying seemingly complex FLs, opening the door to understanding and predicting FLs in general.}, } @article {pmid29686237, year = {2018}, author = {McMullan, M and Rafiqi, M and Kaithakottil, G and Clavijo, BJ and Bilham, L and Orton, E and Percival-Alwyn, L and Ward, BJ and Edwards, A and Saunders, DGO and Garcia Accinelli, G and Wright, J and Verweij, W and Koutsovoulos, G and Yoshida, K and Hosoya, T and Williamson, L and Jennings, P and Ioos, R and Husson, C and Hietala, AM and Vivian-Smith, A and Solheim, H and MaClean, D and Fosker, C and Hall, N and Brown, JKM and Swarbreck, D and Blaxter, M and Downie, JA and Clark, MD}, title = {The ash dieback invasion of Europe was founded by two genetically divergent individuals.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {1000-1008}, pmid = {29686237}, issn = {2397-334X}, abstract = {Accelerating international trade and climate change make pathogen spread an increasing concern. Hymenoscyphus fraxineus, the causal agent of ash dieback, is a fungal pathogen that has been moving across continents and hosts from Asian to European ash. Most European common ash trees (Fraxinus excelsior) are highly susceptible to H. fraxineus, although a minority (~5%) have partial resistance to dieback. Here, we assemble and annotate a H. fraxineus draft genome, which approaches chromosome scale. Pathogen genetic diversity across Europe and in Japan, reveals a strong bottleneck in Europe, though a signal of adaptive diversity remains in key host interaction genes. We find that the European population was founded by two divergent haploid individuals. Divergence between these haplotypes represents the ancestral polymorphism within a large source population. Subsequent introduction from this source would greatly increase adaptive potential of the pathogen. Thus, further introgression of H. fraxineus into Europe represents a potential threat and Europe-wide biological security measures are needed to manage this disease.}, } @article {pmid29686236, year = {2018}, author = {Gifford, DR and Furió, V and Papkou, A and Vogwill, T and Oliver, A and MacLean, RC}, title = {Identifying and exploiting genes that potentiate the evolution of antibiotic resistance.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {1033-1039}, pmid = {29686236}, issn = {2397-334X}, support = {//Wellcome Trust/United Kingdom ; 281591//European Research Council/International ; }, abstract = {There is an urgent need to develop novel approaches for predicting and preventing the evolution of antibiotic resistance. Here, we show that the ability to evolve de novo resistance to a clinically important β-lactam antibiotic, ceftazidime, varies drastically across the genus Pseudomonas. This variation arises because strains possessing the ampR global transcriptional regulator evolve resistance at a high rate. This does not arise because of mutations in ampR. Instead, this regulator potentiates evolution by allowing mutations in conserved peptidoglycan biosynthesis genes to induce high levels of β-lactamase expression. Crucially, blocking this evolutionary pathway by co-administering ceftazidime with the β-lactamase inhibitor avibactam can be used to eliminate pathogenic P. aeruginosa populations before they can evolve resistance. In summary, our study shows that identifying potentiator genes that act as evolutionary catalysts can be used to both predict and prevent the evolution of antibiotic resistance.}, } @article {pmid29686235, year = {2018}, author = {Burgess, MD and Smith, KW and Evans, KL and Leech, D and Pearce-Higgins, JW and Branston, CJ and Briggs, K and Clark, JR and du Feu, CR and Lewthwaite, K and Nager, RG and Sheldon, BC and Smith, JA and Whytock, RC and Willis, SG and Phillimore, AB}, title = {Tritrophic phenological match-mismatch in space and time.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {970-975}, doi = {10.1038/s41559-018-0543-1}, pmid = {29686235}, issn = {2397-334X}, abstract = {Increasing temperatures associated with climate change may generate phenological mismatches that disrupt previously synchronous trophic interactions. Most work on mismatch has focused on temporal trends, whereas spatial variation in the degree of trophic synchrony has largely been neglected, even though the degree to which mismatch varies in space has implications for meso-scale population dynamics and evolution. Here we quantify latitudinal trends in phenological mismatch, using phenological data on an oak-caterpillar-bird system from across the UK. Increasing latitude delays phenology of all species, but more so for oak, resulting in a shorter interval between leaf emergence and peak caterpillar biomass at northern locations. Asynchrony found between peak caterpillar biomass and peak nestling demand of blue tits, great tits and pied flycatchers increases in earlier (warm) springs. There is no evidence of spatial variation in the timing of peak nestling demand relative to peak caterpillar biomass for any species. Phenological mismatch alone is thus unlikely to explain spatial variation in population trends. Given projections of continued spring warming, we predict that temperate forest birds will become increasingly mismatched with peak caterpillar timing. Latitudinal invariance in the direction of mismatch may act as a double-edged sword that presents no opportunities for spatial buffering from the effects of mismatch on population size, but generates spatially consistent directional selection on timing, which could facilitate rapid evolutionary change.}, } @article {pmid29686234, year = {2018}, author = {Varma, SJ and Muchowska, KB and Chatelain, P and Moran, J}, title = {Native iron reduces CO2 to intermediates and end-products of the acetyl-CoA pathway.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {1019-1024}, pmid = {29686234}, issn = {2397-334X}, support = {639170//European Research Council/International ; }, abstract = {Autotrophic theories for the origin of life propose that CO2 was the carbon source for primordial biosynthesis. Among the six known CO2 fixation pathways in nature, the acetyl-CoA (AcCoA; or Wood-Ljungdahl) pathway is the most ancient, and relies on transition metals for catalysis. Modern microbes that use the AcCoA pathway typically fix CO2 with electrons from H2, which requires complex flavin-based electron bifurcation. This presents a paradox: how could primitive metabolic systems have fixed CO2 before the origin of proteins? Here, we show that native transition metals (Fe0, Ni0 and Co0) selectively reduce CO2 to acetate and pyruvate-the intermediates and end-products of the AcCoA pathway-in near millimolar concentrations in water over hours to days using 1-40 bar CO2 and at temperatures from 30 to 100 °C. Geochemical CO2 fixation from native metals could have supplied critical C2 and C3 metabolites before the emergence of enzymes.}, } @article {pmid29686233, year = {2018}, author = {Smith, SM and Kent, DS and Boomsma, JJ and Stow, AJ}, title = {Monogamous sperm storage and permanent worker sterility in a long-lived ambrosia beetle.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {1009-1018}, doi = {10.1038/s41559-018-0533-3}, pmid = {29686233}, issn = {2397-334X}, abstract = {The lifetime monogamy hypothesis claims that the evolution of permanently unmated worker castes always requires maximal full-sibling relatedness to be established first. The long-lived diploid ambrosia beetle Austroplatypus incompertus (Schedl) is known to be highly social, but whether it has lifetime sterile castes has remained unclear. Here we show that the gallery systems of this beetle inside the heartwood of live Eucalyptus trees are always inhabited by a single core family, consisting of a lifetime-inseminated mother, permanently unmated daughter workers, and immatures that are always full siblings to each other and their adult caretakers. Overall sex ratios are even. Males always disperse and only survive as stored sperm, but female offspring either disperse to mate and found their own colony or assume unmated worker roles, probably surviving for many years without any reproductive potential because tarsal loss precludes later dispersal. A well-supported Platypodinae phylogeny has allowed us to infer that parental monogamy evolved before a lifetime-unmated worker caste emerged, confirming the prediction that monogamy and full-sibling relatedness are necessary conditions for the evolution of such workers. The initially very challenging but ultimately long-term stable nesting habitat in live trees appears to have provided the crucial benefit/cost factor for maintaining selection for permanently sterile workers after strict monogamy and lifetime sperm storage had become established in this curculionid coleopteran lineage.}, } @article {pmid29686232, year = {2018}, author = {Davies, NG}, title = {Family matters.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {927-928}, doi = {10.1038/s41559-018-0541-3}, pmid = {29686232}, issn = {2397-334X}, } @article {pmid29686107, year = {2018}, author = {Xu, T and Huo, J and Shao, S and Po, M and Kawano, T and Lu, Y and Wu, M and Zhen, M and Wen, Q}, title = {Descending pathway facilitates undulatory wave propagation in Caenorhabditis elegans through gap junctions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4493-E4502}, pmid = {29686107}, issn = {1091-6490}, support = {MOP93619//CIHR/Canada ; MOP123250//CIHR/Canada ; }, mesh = {Animals ; Animals, Genetically Modified/genetics/*metabolism ; Behavior, Animal ; Caenorhabditis elegans/*physiology ; Caenorhabditis elegans Proteins/genetics/metabolism ; Calcium/metabolism ; Gap Junctions/*physiology ; Interneurons/cytology/*physiology ; *Locomotion ; Motor Activity/*physiology ; Motor Neurons/cytology/*physiology ; Optogenetics ; }, abstract = {Descending signals from the brain play critical roles in controlling and modulating locomotion kinematics. In the Caenorhabditis elegans nervous system, descending AVB premotor interneurons exclusively form gap junctions with the B-type motor neurons that execute forward locomotion. We combined genetic analysis, optogenetic manipulation, calcium imaging, and computational modeling to elucidate the function of AVB-B gap junctions during forward locomotion. First, we found that some B-type motor neurons generate rhythmic activity, constituting distributed oscillators. Second, AVB premotor interneurons use their electric inputs to drive bifurcation of B-type motor neuron dynamics, triggering their transition from stationary to oscillatory activity. Third, proprioceptive couplings between neighboring B-type motor neurons entrain the frequency of body oscillators, forcing coherent bending wave propagation. Despite substantial anatomical differences between the motor circuits of C. elegans and higher model organisms, converging principles govern coordinated locomotion.}, } @article {pmid29686106, year = {2018}, author = {Moriyama, Y and De Robertis, EM}, title = {Embryonic regeneration by relocalization of the Spemann organizer during twinning in Xenopus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4815-E4822}, pmid = {29686106}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Embryo, Nonmammalian/cytology/*physiology ; *Embryonic Development ; Morphogenesis ; Oocytes/cytology/physiology ; *Organizers, Embryonic ; *Regeneration ; Signal Transduction ; *Twinning, Monozygotic ; Xenopus Proteins/*metabolism ; Xenopus laevis/*embryology/physiology ; }, abstract = {The formation of identical twins from a single egg has fascinated developmental biologists for a very long time. Previous work had shown that Xenopus blastulae bisected along the dorsal-ventral (D-V) midline (i.e., the sagittal plane) could generate twins but at very low frequencies. Here, we have improved this method by using an eyelash knife and changing saline solutions, reaching frequencies of twinning of 50% or more. This allowed mechanistic analysis of the twinning process. We unexpectedly observed that the epidermis of the resulting twins was asymmetrically pigmented at the tailbud stage of regenerating tadpoles. This pigment was entirely of maternal (oocyte) origin. Bisecting the embryo generated a large wound, which closed from all directions within 60 minutes, bringing cells normally fated to become Spemann organizer in direct contact with predicted ventral-most cells. Lineage-tracing analyses at the four-cell stage showed that in regenerating embryos midline tissues originated from the dorsal half, while the epidermis was entirely of ventral origin. Labeling of D-V segments at the 16-cell stage showed that the more pigmented epidermis originated from the ventral-most cells, while the less-pigmented epidermis arose from the adjoining ventral segment. This suggested a displacement of the organizer by 90°. Studies with the marker Chordin and phospho-Smad1/5/8 showed that in half embryos a new D-V gradient is intercalated at the site of the missing half. The displacement of self-organizing morphogen gradients uncovered here may help us understand not only twin formation in amphibians, but also rare cases of polyembryony.}, } @article {pmid29686105, year = {2018}, author = {Takayama, KI and Suzuki, T and Fujimura, T and Takahashi, S and Inoue, S}, title = {COBLL1 modulates cell morphology and facilitates androgen receptor genomic binding in advanced prostate cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4975-4980}, pmid = {29686105}, issn = {1091-6490}, mesh = {Animals ; CDC2 Protein Kinase/genetics/metabolism ; Cell Line, Tumor ; *Cell Movement ; Cell Nucleus/genetics/*metabolism/pathology ; Gene Expression Profiling ; Humans ; Male ; Mice, Inbred BALB C ; Mice, Nude ; Multiprotein Complexes/genetics/*metabolism ; Neoplasm Proteins/genetics/*metabolism ; Prostatic Neoplasms, Castration-Resistant/diagnosis/genetics/*metabolism/pathology ; Protein Domains ; Receptors, Androgen/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Androgen receptor (AR) signaling is essential for prostate cancer progression and acquiring resistance to hormone therapy. However, the molecular pathogenesis through AR activation has not been fully understood. We performed integrative transcriptomic analysis to compare the AR program in a castration-resistant prostate cancer (CRPC) model with that in their parental hormone-sensitive cells. We found that the gene cordon-bleu-like 1 (COBLL1) is highly induced by AR in CRPC model cells. The expression of COBLL1 that possesses an actin-binding domain is up-regulated in clinical prostate cancer tissues and is associated with a poor prognosis for prostate cancer patients. COBLL1 is involved in the cancer cell morphogenesis to a neuron-like cell shape observed in the CRPC model cells, promoting cell growth and migration. Moreover, nuclear COBLL1 interacts with AR to enhance complex formation with CDK1 and facilitates AR phosphorylation for genomic binding in CRPC model cells. Thus, our findings showed the mechanistic relevance of cordon-bleu proteins during the AR-mediated progression to CRPC.}, } @article {pmid29686104, year = {2018}, author = {Girard, C and Roelens, B and Zawadzki, KA and Villeneuve, AM}, title = {Interdependent and separable functions of Caenorhabditis elegans MRN-C complex members couple formation and repair of meiotic DSBs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4443-E4452}, pmid = {29686104}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 GM067268/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/embryology/*genetics ; Caenorhabditis elegans Proteins/*genetics/metabolism ; *DNA Breaks, Double-Stranded ; *DNA End-Joining Repair ; Embryo, Nonmammalian/cytology/*metabolism ; *Homologous Recombination ; *Meiosis ; }, abstract = {Faithful inheritance of genetic information through sexual reproduction relies on the formation of crossovers between homologous chromosomes during meiosis, which, in turn, relies on the formation and repair of numerous double-strand breaks (DSBs). As DSBs pose a potential threat to the genome, mechanisms that ensure timely and error-free DSB repair are crucial for successful meiosis. Here, we identify NBS-1, the Caenorhabditis elegans ortholog of the NBS1 (mutated in Nijmegen Breakage Syndrome) subunit of the conserved MRE11-RAD50-NBS1/Xrs2 (MRN) complex, as a key mediator of DSB repair via homologous recombination (HR) during meiosis. Loss of nbs-1 leads to severely reduced loading of recombinase RAD-51, ssDNA binding protein RPA, and pro-crossover factor COSA-1 during meiotic prophase progression; aggregated and fragmented chromosomes at the end of meiotic prophase; and 100% progeny lethality. These phenotypes reflect a role for NBS-1 in processing of meiotic DSBs for HR that is shared with its interacting partners MRE-11-RAD-50 and COM-1 (ortholog of Com1/Sae2/CtIP). Unexpectedly, in contrast to MRE-11 and RAD-50, NBS-1 is not required for meiotic DSB formation. Meiotic defects of the nbs-1 mutant are partially suppressed by abrogation of the nonhomologous end-joining (NHEJ) pathway, indicating a role for NBS-1 in antagonizing NHEJ during meiosis. Our data further reveal that NBS-1 and COM-1 play distinct roles in promoting HR and antagonizing NHEJ. We propose a model in which different components of the MRN-C complex work together to couple meiotic DSB formation with efficient and timely engagement of HR, thereby ensuring crossover formation and restoration of genome integrity before the meiotic divisions.}, } @article {pmid29686103, year = {2018}, author = {Li, Z and Takahashi, Y and Scavo, A and Brandt, B and Nguyen, D and Rieu, P and Schroeder, JI}, title = {Abscisic acid-induced degradation of Arabidopsis guanine nucleotide exchange factor requires calcium-dependent protein kinases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4522-E4531}, pmid = {29686103}, issn = {1091-6490}, support = {P42 ES010337/ES/NIEHS NIH HHS/United States ; }, mesh = {Abscisic Acid/*pharmacology ; Arabidopsis/drug effects/genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Calcium-Calmodulin-Dependent Protein Kinases/genetics/*metabolism ; Gene Expression Regulation, Plant/*drug effects ; Guanine Nucleotide Exchange Factors/genetics/*metabolism ; Phosphorylation/drug effects ; Plant Growth Regulators/pharmacology ; Plant Roots/genetics/*growth & development/metabolism ; Protein Transport ; Proteolysis/*drug effects ; Signal Transduction/drug effects ; }, abstract = {Abscisic acid (ABA) plays essential roles in plant development and responses to environmental stress. ABA induces subcellular translocation and degradation of the guanine nucleotide exchange factor RopGEF1, thus facilitating ABA core signal transduction. However, the underlying mechanisms for ABA-triggered RopGEF1 trafficking/degradation remain unknown. Studies have revealed that RopGEFs associate with receptor-like kinases to convey developmental signals to small ROP GTPases. However, how the activities of RopGEFs are modulated is not well understood. Type 2C protein phosphatases stabilize the RopGEF1 protein, indicating that phosphorylation may trigger RopGEF1 trafficking and degradation. We have screened inhibitors followed by several protein kinase mutants and find that quadruple-mutant plants in the Arabidopsis calcium-dependent protein kinases (CPKs) cpk3/4/6/11 disrupt ABA-induced trafficking and degradation of RopGEF1. Moreover, cpk3/4/6/11 partially impairs ABA inhibition of cotyledon emergence. Several CPKs interact with RopGEF1. CPK4 binds to and phosphorylates RopGEF1 and promotes the degradation of RopGEF1. CPK-mediated phosphorylation of RopGEF1 at specific N-terminal serine residues causes the degradation of RopGEF1 and mutation of these sites also compromises the RopGEF1 overexpression phenotype in root hair development in Arabidopsis Our findings establish the physiological and molecular functions and relevance of CPKs in regulation of RopGEF1 and illuminate physiological roles of a CPK-GEF-ROP module in ABA signaling and plant development. We further discuss that CPK-dependent RopGEF degradation during abiotic stress could provide a mechanism for down-regulation of RopGEF-dependent growth responses.}, } @article {pmid29686102, year = {2018}, author = {Ferdowsi, B and Ortiz, CP and Jerolmack, DJ}, title = {Glassy dynamics of landscape evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4827-4832}, pmid = {29686102}, issn = {1091-6490}, support = {P42 ES023720/ES/NIEHS NIH HHS/United States ; }, mesh = {*Models, Theoretical ; *Soil ; }, abstract = {Soil creeps imperceptibly downhill, but also fails catastrophically to create landslides. Despite the importance of these processes as hazards and in sculpting landscapes, there is no agreed-upon model that captures the full range of behavior. Here we examine the granular origins of hillslope soil transport by discrete element method simulations and reanalysis of measurements in natural landscapes. We find creep for slopes below a critical gradient, where average particle velocity (sediment flux) increases exponentially with friction coefficient (gradient). At critical gradient there is a continuous transition to a dense-granular flow rheology. Slow earthflows and landslides thus exhibit glassy dynamics characteristic of a wide range of disordered materials; they are described by a two-phase flux equation that emerges from grain-scale friction alone. This glassy model reproduces topographic profiles of natural hillslopes, showing its promise for predicting hillslope evolution over geologic timescales.}, } @article {pmid29686101, year = {2018}, author = {Clark, CM and Costa, MS and Sanchez, LM and Murphy, BT}, title = {Coupling MALDI-TOF mass spectrometry protein and specialized metabolite analyses to rapidly discriminate bacterial function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4981-4986}, pmid = {29686101}, issn = {1091-6490}, support = {K12 HD055892/HD/NICHD NIH HHS/United States ; }, mesh = {Bacillus subtilis/classification/*metabolism ; Bacterial Proteins/analysis/*metabolism ; Bacterial Typing Techniques/*methods ; Deferoxamine/analysis/metabolism ; Micromonospora/classification/*metabolism ; Peptides, Cyclic/analysis/metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {For decades, researchers have lacked the ability to rapidly correlate microbial identity with bacterial metabolism. Since specialized metabolites are critical to bacterial function and survival in the environment, we designed a data acquisition and bioinformatics technique (IDBac) that utilizes in situ matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) to analyze protein and specialized metabolite spectra recorded from single bacterial colonies picked from agar plates. We demonstrated the power of our approach by discriminating between two Bacillus subtilis strains in <30 min solely on the basis of their differential ability to produce cyclic peptide antibiotics surfactin and plipastatin, caused by a single frameshift mutation. Next, we used IDBac to detect subtle intraspecies differences in the production of metal scavenging acyl-desferrioxamines in a group of eight freshwater Micromonospora isolates that share >99% sequence similarity in the 16S rRNA gene. Finally, we used IDBac to simultaneously extract protein and specialized metabolite MS profiles from unidentified Lake Michigan sponge-associated bacteria isolated from an agar plate. In just 3 h, we created hierarchical protein MS groupings of 11 environmental isolates (10 MS replicates each, for a total of 110 spectra) that accurately mirrored phylogenetic groupings. We further distinguished isolates within these groupings, which share nearly identical 16S rRNA gene sequence identity, based on interspecies and intraspecies differences in specialized metabolite production. IDBac is an attempt to couple in situ MS analyses of protein content and specialized metabolite production to allow for facile discrimination of closely related bacterial colonies.}, } @article {pmid29686100, year = {2018}, author = {DiPrete, TA and Burik, CAP and Koellinger, PD}, title = {Genetic instrumental variable regression: Explaining socioeconomic and health outcomes in nonexperimental data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E4970-E4979}, pmid = {29686100}, issn = {1091-6490}, support = {647648//European Research Council/International ; RC2 AG036495/AG/NIA NIH HHS/United States ; RC4 AG039029/AG/NIA NIH HHS/United States ; U01 AG009740/AG/NIA NIH HHS/United States ; }, mesh = {Body Height/physiology ; Educational Status ; *Genetic Pleiotropy ; *Genetic Variation ; *Genome-Wide Association Study/standards/statistics & numerical data ; Humans ; Outcome Assessment (Health Care) ; *Socioeconomic Factors ; }, abstract = {Identifying causal effects in nonexperimental data is an enduring challenge. One proposed solution that recently gained popularity is the idea to use genes as instrumental variables [i.e., Mendelian randomization (MR)]. However, this approach is problematic because many variables of interest are genetically correlated, which implies the possibility that many genes could affect both the exposure and the outcome directly or via unobserved confounding factors. Thus, pleiotropic effects of genes are themselves a source of bias in nonexperimental data that would also undermine the ability of MR to correct for endogeneity bias from nongenetic sources. Here, we propose an alternative approach, genetic instrumental variable (GIV) regression, that provides estimates for the effect of an exposure on an outcome in the presence of pleiotropy. As a valuable byproduct, GIV regression also provides accurate estimates of the chip heritability of the outcome variable. GIV regression uses polygenic scores (PGSs) for the outcome of interest which can be constructed from genome-wide association study (GWAS) results. By splitting the GWAS sample for the outcome into nonoverlapping subsamples, we obtain multiple indicators of the outcome PGSs that can be used as instruments for each other and, in combination with other methods such as sibling fixed effects, can address endogeneity bias from both pleiotropy and the environment. In two empirical applications, we demonstrate that our approach produces reasonable estimates of the chip heritability of educational attainment (EA) and show that standard regression and MR provide upwardly biased estimates of the effect of body height on EA.}, } @article {pmid29686099, year = {2018}, author = {Matsuyama, S and Kage, Y and Fujimoto, N and Ushijima, T and Tsuruda, T and Kitamura, K and Shiose, A and Asada, Y and Sumimoto, H and Takeya, R}, title = {Interaction between cardiac myosin-binding protein C and formin Fhod3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4386-E4395}, pmid = {29686099}, issn = {1091-6490}, mesh = {Animals ; Cardiomyopathy, Hypertrophic/genetics/*metabolism/pathology ; Carrier Proteins/genetics/*metabolism ; Mice ; Mice, Transgenic ; Microfilament Proteins/genetics/*metabolism ; Myocardium/*metabolism/pathology ; Protein Binding ; Protein Domains ; Protein Transport ; Sarcomeres/genetics/*metabolism/pathology ; }, abstract = {Mutations in cardiac myosin-binding protein C (cMyBP-C) are a major cause of familial hypertrophic cardiomyopathy. Although cMyBP-C has been considered to regulate the cardiac function via cross-bridge arrangement at the C-zone of the myosin-containing A-band, the mechanism by which cMyBP-C functions remains unclear. We identified formin Fhod3, an actin organizer essential for the formation and maintenance of cardiac sarcomeres, as a cMyBP-C-binding protein. The cardiac-specific N-terminal Ig-like domain of cMyBP-C directly interacts with the cardiac-specific N-terminal region of Fhod3. The interaction seems to direct the localization of Fhod3 to the C-zone, since a noncardiac Fhod3 variant lacking the cMyBP-C-binding region failed to localize to the C-zone. Conversely, the cardiac variant of Fhod3 failed to localize to the C-zone in the cMyBP-C-null mice, which display a phenotype of hypertrophic cardiomyopathy. The cardiomyopathic phenotype of cMyBP-C-null mice was further exacerbated by Fhod3 overexpression with a defect of sarcomere integrity, whereas that was partially ameliorated by a reduction in the Fhod3 protein levels, suggesting that Fhod3 has a deleterious effect on cardiac function under cMyBP-C-null conditions where Fhod3 is aberrantly mislocalized. Together, these findings suggest the possibility that Fhod3 contributes to the pathogenesis of cMyBP-C-related cardiomyopathy and that Fhod3 is critically involved in cMyBP-C-mediated regulation of cardiac function via direct interaction.}, } @article {pmid29686098, year = {2018}, author = {Maezawa, S and Hasegawa, K and Yukawa, M and Kubo, N and Sakashita, A and Alavattam, KG and Sin, HS and Kartashov, AV and Sasaki, H and Barski, A and Namekawa, SH}, title = {Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4957-4962}, pmid = {29686098}, issn = {1091-6490}, support = {DP2 GM119134/GM/NIGMS NIH HHS/United States ; K22 HL098691/HL/NHLBI NIH HHS/United States ; R01 GM098605/GM/NIGMS NIH HHS/United States ; R01 GM122776/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Embryonic Development ; Gene Expression Regulation, Developmental ; Histones/genetics/*metabolism ; Male ; Mice ; Mice, Knockout ; Polycomb-Group Proteins/genetics/*metabolism ; *Promoter Regions, Genetic ; Spermatogenesis/*physiology ; Spermatogonia/cytology/*metabolism ; }, abstract = {Repressive H3K27me3 and active H3K4me2/3 together form bivalent chromatin domains, molecular hallmarks of developmental potential. In the male germline, these domains are thought to persist into sperm to establish totipotency in the next generation. However, it remains unknown how H3K27me3 is established on specific targets in the male germline. Here, we demonstrate that a germline-specific Polycomb protein, SCML2, binds to H3K4me2/3-rich hypomethylated promoters in undifferentiated spermatogonia to facilitate H3K27me3. Thus, SCML2 establishes bivalent domains in the male germline of mice. SCML2 regulates two major classes of bivalent domains: Class I domains are established on developmental regulator genes that are silent throughout spermatogenesis, while class II domains are established on somatic genes silenced during late spermatogenesis. We propose that SCML2-dependent H3K27me3 in the male germline prepares the expression of developmental regulator and somatic genes in embryonic development.}, } @article {pmid29686097, year = {2018}, author = {Hangasky, JA and Iavarone, AT and Marletta, MA}, title = {Reactivity of O2 versus H2O2 with polysaccharide monooxygenases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4915-4920}, pmid = {29686097}, issn = {1091-6490}, support = {S10 OD020062/OD/NIH HHS/United States ; }, mesh = {Catalytic Domain ; Copper/chemistry ; Fungal Proteins/*chemistry ; Glycoside Hydrolases/*chemistry ; Hydrogen Peroxide/*chemistry ; Mixed Function Oxygenases/*chemistry ; Oxygen/*chemistry ; Sordariales/*enzymology ; }, abstract = {Enzymatic conversion of polysaccharides into lower-molecular-weight, soluble oligosaccharides is dependent on the action of hydrolytic and oxidative enzymes. Polysaccharide monooxygenases (PMOs) use an oxidative mechanism to break the glycosidic bond of polymeric carbohydrates, thereby disrupting the crystalline packing and creating new chain ends for hydrolases to depolymerize and degrade recalcitrant polysaccharides. PMOs contain a mononuclear Cu(II) center that is directly involved in C-H bond hydroxylation. Molecular oxygen was the accepted cosubstrate utilized by this family of enzymes until a recent report indicated reactivity was dependent on H2O2 Reported here is a detailed analysis of PMO reactivity with H2O2 and O2, in conjunction with high-resolution MS measurements. The cosubstrate utilized by the enzyme is dependent on the assay conditions. PMOs will directly reduce O2 in the coupled hydroxylation of substrate (monooxygenase activity) and will also utilize H2O2 (peroxygenase activity) produced from the uncoupled reduction of O2 Both cosubstrates require Cu reduction to Cu(I), but the reaction with H2O2 leads to nonspecific oxidation of the polysaccharide that is consistent with the generation of a hydroxyl radical-based mechanism in Fenton-like chemistry, while the O2 reaction leads to regioselective substrate oxidation using an enzyme-bound Cu/O2 reactive intermediate. Moreover, H2O2 does not influence the ability of secretome from Neurospora crassa to degrade Avicel, providing evidence that molecular oxygen is a physiologically relevant cosubstrate for PMOs.}, } @article {pmid29686096, year = {2018}, author = {Viegas, J}, title = {Profile of James C. Liao.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4807-4809}, pmid = {29686096}, issn = {1091-6490}, mesh = {History, 20th Century ; History, 21st Century ; Humans ; Metabolic Engineering/*history ; Portraits as Topic ; Synthetic Biology/*history ; Systems Biology/*history ; }, } @article {pmid29686095, year = {2018}, author = {Byrne, MP and O'Gorman, PA}, title = {Trends in continental temperature and humidity directly linked to ocean warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4863-4868}, pmid = {29686095}, issn = {1091-6490}, abstract = {In recent decades, the land surface has warmed substantially more than the ocean surface, and relative humidity has fallen over land. Amplified warming and declining relative humidity over land are also dominant features of future climate projections, with implications for climate-change impacts. An emerging body of research has shown how constraints from atmospheric dynamics and moisture budgets are important for projected future land-ocean contrasts, but these ideas have not been used to investigate temperature and humidity records over recent decades. Here we show how both the temperature and humidity changes observed over land between 1979 and 2016 are linked to warming over neighboring oceans. A simple analytical theory, based on atmospheric dynamics and moisture transport, predicts equal changes in moist static energy over land and ocean and equal fractional changes in specific humidity over land and ocean. The theory is shown to be consistent with the observed trends in land temperature and humidity given the warming over ocean. Amplified land warming is needed for the increase in moist static energy over drier land to match that over ocean, and land relative humidity decreases because land specific humidity is linked via moisture transport to the weaker warming over ocean. However, there is considerable variability about the best-fit trend in land relative humidity that requires further investigation and which may be related to factors such as changes in atmospheric circulations and land-surface properties.}, } @article {pmid29686094, year = {2018}, author = {Bol, T and de Vaan, M and van de Rijt, A}, title = {The Matthew effect in science funding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4887-4890}, pmid = {29686094}, issn = {1091-6490}, abstract = {A classic thesis is that scientific achievement exhibits a "Matthew effect": Scientists who have previously been successful are more likely to succeed again, producing increasing distinction. We investigate to what extent the Matthew effect drives the allocation of research funds. To this end, we assembled a dataset containing all review scores and funding decisions of grant proposals submitted by recent PhDs in a €2 billion granting program. Analyses of review scores reveal that early funding success introduces a growing rift, with winners just above the funding threshold accumulating more than twice as much research funding (€180,000) during the following eight years as nonwinners just below it. We find no evidence that winners' improved funding chances in subsequent competitions are due to achievements enabled by the preceding grant, which suggests that early funding itself is an asset for acquiring later funding. Surprisingly, however, the emergent funding gap is partly created by applicants, who, after failing to win one grant, apply for another grant less often.}, } @article {pmid29686093, year = {2018}, author = {}, title = {Correction for Alder et al., Diagnostic utility of telomere length testing in a hospital-based setting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4312}, doi = {10.1073/pnas.1805407115}, pmid = {29686093}, issn = {1091-6490}, } @article {pmid29686092, year = {2018}, author = {Hlusko, LJ and Carlson, JP and Chaplin, G and Elias, SA and Hoffecker, JF and Huffman, M and Jablonski, NG and Monson, TA and O'Rourke, DH and Pilloud, MA and Scott, GR}, title = {Environmental selection during the last ice age on the mother-to-infant transmission of vitamin D and fatty acids through breast milk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4426-E4432}, pmid = {29686092}, issn = {1091-6490}, mesh = {Alleles ; *Cold Climate ; *Edar Receptor/genetics/metabolism ; Fatty Acids/*metabolism ; Female ; Humans ; Male ; Mammary Glands, Human/anatomy & histology/metabolism ; Maternal-Fetal Exchange/*physiology ; Milk, Human/*metabolism ; Pregnancy ; Selection, Genetic/*physiology ; Vitamin D/*metabolism ; }, abstract = {Because of the ubiquitous adaptability of our material culture, some human populations have occupied extreme environments that intensified selection on existing genomic variation. By 32,000 years ago, people were living in Arctic Beringia, and during the Last Glacial Maximum (LGM; 28,000-18,000 y ago), they likely persisted in the Beringian refugium. Such high latitudes provide only very low levels of UV radiation, and can thereby lead to dangerously low levels of biosynthesized vitamin D. The physiological effects of vitamin D deficiency range from reduced dietary absorption of calcium to a compromised immune system and modified adipose tissue function. The ectodysplasin A receptor (EDAR) gene has a range of pleiotropic effects, including sweat gland density, incisor shoveling, and mammary gland ductal branching. The frequency of the human-specific EDAR V370A allele appears to be uniquely elevated in North and East Asian and New World populations due to a bout of positive selection likely to have occurred circa 20,000 y ago. The dental pleiotropic effects of this allele suggest an even higher occurrence among indigenous people in the Western Hemisphere before European colonization. We hypothesize that selection on EDAR V370A occurred in the Beringian refugium because it increases mammary ductal branching, and thereby may amplify the transfer of critical nutrients in vitamin D-deficient conditions to infants via mothers' milk. This hypothesized selective context for EDAR V370A was likely intertwined with selection on the fatty acid desaturase (FADS) gene cluster because it is known to modulate lipid profiles transmitted to milk from a vitamin D-rich diet high in omega-3 fatty acids.}, } @article {pmid29686091, year = {2018}, author = {Shropshire, JD and On, J and Layton, EM and Zhou, H and Bordenstein, SR}, title = {One prophage WO gene rescues cytoplasmic incompatibility in Drosophila melanogaster.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4987-4991}, pmid = {29686091}, issn = {1091-6490}, support = {R21 HD086833/HD/NICHD NIH HHS/United States ; P60 DK020593/DK/NIDDK NIH HHS/United States ; P30 DK058404/DK/NIDDK NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; P30 DK020593/DK/NIDDK NIH HHS/United States ; P30 CA068485/CA/NCI NIH HHS/United States ; R01 AI132581/AI/NIAID NIH HHS/United States ; U24 DK059637/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Drosophila melanogaster ; *Embryo, Nonmammalian/metabolism/microbiology ; Male ; *Prophages ; *Spermatozoa/metabolism/microbiology ; *Wolbachia/genetics/metabolism/virology ; }, abstract = {Wolbachia are maternally inherited, intracellular bacteria at the forefront of vector control efforts to curb arbovirus transmission. In international field trials, the cytoplasmic incompatibility (CI) drive system of wMel Wolbachia is deployed to replace target vector populations, whereby a Wolbachia-induced modification of the sperm genome kills embryos. However, Wolbachia in the embryo rescue the sperm genome impairment, and therefore CI results in a strong fitness advantage for infected females that transmit the bacteria to offspring. The two genes responsible for the wMel-induced sperm modification of CI, cifA and cifB, were recently identified in the eukaryotic association module of prophage WO, but the genetic basis of rescue is unresolved. Here we use transgenic and cytological approaches to demonstrate that maternal cifA expression independently rescues CI and nullifies embryonic death caused by wMel Wolbachia in Drosophila melanogaster Discovery of cifA as the rescue gene and previously one of two CI induction genes establishes a "Two-by-One" model that underpins the genetic basis of CI. Results highlight the central role of prophage WO in shaping Wolbachia phenotypes that are significant to arthropod evolution and vector control.}, } @article {pmid29686090, year = {2018}, author = {Ge, X and Mandava, CS and Lind, C and Åqvist, J and Sanyal, S}, title = {Complementary charge-based interaction between the ribosomal-stalk protein L7/12 and IF2 is the key to rapid subunit association.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4649-4654}, pmid = {29686090}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Escherichia coli/*chemistry/genetics/metabolism ; Escherichia coli Proteins/*chemistry/genetics/metabolism ; *Molecular Docking Simulation ; *Molecular Dynamics Simulation ; Mutation ; *Peptide Chain Initiation, Translational ; Prokaryotic Initiation Factor-2/*chemistry/genetics/metabolism ; Ribosomal Proteins/*chemistry/genetics/metabolism ; }, abstract = {The interaction between the ribosomal-stalk protein L7/12 (L12) and initiation factor 2 (IF2) is essential for rapid subunit association, but the underlying mechanism is unknown. Here, we have characterized the L12-IF2 interaction on Escherichia coli ribosomes using site-directed mutagenesis, fast kinetics, and molecular dynamics (MD) simulations. Fifteen individual point mutations were introduced into the C-terminal domain of L12 (L12-CTD) at helices 4 and 5, which constitute the common interaction site for translational GTPases. In parallel, 15 point mutations were also introduced into IF2 between the G4 and G5 motifs, which we hypothesized as the potential L12 interaction sites. The L12 and IF2 mutants were tested in ribosomal subunit association assay in a stopped-flow instrument. Those amino acids that caused defective subunit association upon substitution were identified as the molecular determinants of L12-IF2 interaction. Further, MD simulations of IF2 docked onto the L12-CTD pinpointed the exact interacting partners-all of which were positively charged on L12 and negatively charged on IF2, connected by salt bridges. Lastly, we tested two pairs of charge-reversed mutants of L12 and IF2, which significantly restored the yield and the rate of formation of the 70S initiation complex. We conclude that complementary charge-based interaction between L12-CTD and IF2 is the key for fast subunit association. Considering the homology of the G domain, similar mechanisms may apply for L12 interactions with other translational GTPases.}, } @article {pmid29686089, year = {2018}, author = {Lehtimäki, J and Sinkko, H and Hielm-Björkman, A and Salmela, E and Tiira, K and Laatikainen, T and Mäkeläinen, S and Kaukonen, M and Uusitalo, L and Hanski, I and Lohi, H and Ruokolainen, L}, title = {Skin microbiota and allergic symptoms associate with exposure to environmental microbes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4897-4902}, pmid = {29686089}, issn = {1091-6490}, mesh = {Animals ; Dogs ; *Environmental Exposure ; Female ; Humans ; *Hypersensitivity/immunology/microbiology ; Male ; Mice ; Microbiota/*immunology ; *Skin/immunology/microbiology ; Social Planning ; Urban Renewal ; }, abstract = {A rural environment and farming lifestyle are known to provide protection against allergic diseases. This protective effect is expected to be mediated via exposure to environmental microbes that are needed to support a normal immune tolerance. However, the triangle of interactions between environmental microbes, host microbiota, and immune system remains poorly understood. Here, we have studied these interactions using a canine model (two breeds, n = 169), providing an intermediate approach between complex human studies and artificial mouse model studies. We show that the skin microbiota reflects both the living environment and the lifestyle of a dog. Remarkably, the prevalence of spontaneous allergies is also associated with residential environment and lifestyle, such that allergies are most common among urban dogs living in single-person families without other animal contacts, and least common among rural dogs having opposite lifestyle features. Thus, we show that living environment and lifestyle concurrently associate with skin microbiota and allergies, suggesting that these factors might be causally related. Moreover, microbes commonly found on human skin tend to dominate the urban canine skin microbiota, while environmental microbes are rich in the rural canine skin microbiota. This in turn suggests that skin microbiota is a feasible indicator of exposure to environmental microbes. As short-term exposure to environmental microbes via exercise is not associated with allergies, we conclude that prominent and sustained exposure to environmental microbiotas should be promoted by urban planning and lifestyle changes to support health of urban populations.}, } @article {pmid29686088, year = {2018}, author = {Ueda, K and Kim, HJ and Zhao, J and Song, Y and Dunaief, JL and Sparrow, JR}, title = {Iron promotes oxidative cell death caused by bisretinoids of retina.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4963-4968}, pmid = {29686088}, issn = {1091-6490}, support = {P30 EY019007/EY/NEI NIH HHS/United States ; R01 EY012951/EY/NEI NIH HHS/United States ; R01 EY028131/EY/NEI NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/deficiency ; Animals ; Cell Death/drug effects/genetics ; Deferiprone ; Iron ; Iron Chelating Agents/pharmacology ; Lipofuscin/genetics/metabolism ; Mice ; Mice, Knockout ; Pyridones/pharmacology ; Retinal Pigment Epithelium/*metabolism/pathology ; Retinaldehyde/genetics/metabolism ; Retinoids/*metabolism ; }, abstract = {Intracellular Fe plays a key role in redox active energy and electron transfer. We sought to understand how Fe levels impact the retina, given that retinal pigment epithelial (RPE) cells are also challenged by accumulations of vitamin A aldehyde adducts (bisretinoid lipofuscin) that photogenerate reactive oxygen species and photodecompose into damaging aldehyde- and dicarbonyl-bearing species. In mice treated with the Fe chelator deferiprone (DFP), intracellular Fe levels, as reflected in transferrin receptor mRNA expression, were reduced. DFP-treated albino Abca4-/- and agouti wild-type mice exhibited elevated bisretinoid levels as measured by high-performance liquid chromatography or noninvasively by quantitative fundus autofluorescence. Thinning of the outer nuclear layer, a parameter indicative of the loss of photoreceptor cell viability, was also reduced in DFP-treated albino Abca4-/- In contrast to the effects of the Fe chelator, mice burdened with increased intracellular Fe in RPE due to deficiency in the Fe export proteins hephaestin and ceruloplasmin, presented with reduced bisretinoid levels. These findings indicate that intracellular Fe promotes bisretinoid oxidation and degradation. This interpretation was supported by experiments showing that DFP decreased the oxidative/degradation of the bisretinoid A2E in the presence of light and reduced cell death in cell-based experiments. Moreover, light-independent oxidation and degradation of A2E by Fenton chemistry products were evidenced by the consumption of A2E, release of dicarbonyls, and generation of oxidized A2E species in cell-free assays.}, } @article {pmid29686087, year = {2018}, author = {Wang, HX and Song, Z and Lao, YH and Xu, X and Gong, J and Cheng, D and Chakraborty, S and Park, JS and Li, M and Huang, D and Yin, L and Cheng, J and Leong, KW}, title = {Nonviral gene editing via CRISPR/Cas9 delivery by membrane-disruptive and endosomolytic helical polypeptide.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4903-4908}, pmid = {29686087}, issn = {1091-6490}, support = {R01 AI096305/AI/NIAID NIH HHS/United States ; R01 GM110494/GM/NIGMS NIH HHS/United States ; R01 HL109442/HL/NHLBI NIH HHS/United States ; UH3 TR000505/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; *CRISPR-Cas Systems ; *Cell-Penetrating Peptides/chemistry/pharmacology ; Gene Editing/*methods ; *Gene Transfer Techniques ; HEK293 Cells ; HeLa Cells ; Humans ; K562 Cells ; Mice ; NIH 3T3 Cells ; Nanoparticles/*chemistry ; *Plasmids/chemistry/genetics/pharmacology ; }, abstract = {Effective and safe delivery of the CRISPR/Cas9 gene-editing elements remains a challenge. Here we report the development of PEGylated nanoparticles (named P-HNPs) based on the cationic α-helical polypeptide poly(γ-4-((2-(piperidin-1-yl)ethyl)aminomethyl)benzyl-l-glutamate) for the delivery of Cas9 expression plasmid and sgRNA to various cell types and gene-editing scenarios. The cell-penetrating α-helical polypeptide enhanced cellular uptake and promoted escape of pCas9 and/or sgRNA from the endosome and transport into the nucleus. The colloidally stable P-HNPs achieved a Cas9 transfection efficiency up to 60% and sgRNA uptake efficiency of 67.4%, representing an improvement over existing polycation-based gene delivery systems. After performing single or multiplex gene editing with an efficiency up to 47.3% in vitro, we demonstrated that P-HNPs delivering Cas9 plasmid/sgRNA targeting the polo-like kinase 1 (Plk1) gene achieved 35% gene deletion in HeLa tumor tissue to reduce the Plk1 protein level by 66.7%, thereby suppressing the tumor growth by >71% and prolonging the animal survival rate to 60% within 60 days. Capable of delivering Cas9 plasmids to various cell types to achieve multiplex gene knock-out, gene knock-in, and gene activation in vitro and in vivo, the P-HNP system offers a versatile gene-editing platform for biological research and therapeutic applications.}, } @article {pmid29686086, year = {2018}, author = {Stringlis, IA and Yu, K and Feussner, K and de Jonge, R and Van Bentum, S and Van Verk, MC and Berendsen, RL and Bakker, PAHM and Feussner, I and Pieterse, CMJ}, title = {MYB72-dependent coumarin exudation shapes root microbiome assembly to promote plant health.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {22}, pages = {E5213-E5222}, pmid = {29686086}, issn = {1091-6490}, support = {269072//European Research Council/International ; }, mesh = {Arabidopsis/metabolism/physiology ; Arabidopsis Proteins/*metabolism ; Fusarium/metabolism ; Iron/metabolism ; Metabolome ; Microbiota/*physiology ; Plant Roots/*metabolism/*microbiology ; Pseudomonas/metabolism ; Rhizosphere ; Scopoletin/*metabolism ; Transcription Factors/*metabolism ; Verticillium/metabolism ; }, abstract = {Plant roots nurture a tremendous diversity of microbes via exudation of photosynthetically fixed carbon sources. In turn, probiotic members of the root microbiome promote plant growth and protect the host plant against pathogens and pests. In the Arabidopsis thaliana-Pseudomonas simiae WCS417 model system the root-specific transcription factor MYB72 and the MYB72-controlled β-glucosidase BGLU42 emerged as important regulators of beneficial rhizobacteria-induced systemic resistance (ISR) and iron-uptake responses. MYB72 regulates the biosynthesis of iron-mobilizing fluorescent phenolic compounds, after which BGLU42 activity is required for their excretion into the rhizosphere. Metabolite fingerprinting revealed the antimicrobial coumarin scopoletin as a dominant metabolite that is produced in the roots and excreted into the rhizosphere in a MYB72- and BGLU42-dependent manner. Shotgun-metagenome sequencing of root-associated microbiota of Col-0, myb72, and the scopoletin biosynthesis mutant f6'h1 showed that scopoletin selectively impacts the assembly of the microbial community in the rhizosphere. We show that scopoletin selectively inhibits the soil-borne fungal pathogens Fusarium oxysporum and Verticillium dahliae, while the growth-promoting and ISR-inducing rhizobacteria P. simiae WCS417 and Pseudomonas capeferrum WCS358 are highly tolerant of the antimicrobial effect of scopoletin. Collectively, our results demonstrate a role for coumarins in microbiome assembly and point to a scenario in which plants and probiotic rhizobacteria join forces to trigger MYB72/BGLU42-dependent scopolin production and scopoletin excretion, resulting in improved niche establishment for the microbial partner and growth and immunity benefits for the host plant.}, } @article {pmid29686085, year = {2018}, author = {Ruiz-Martínez, Á and Bartol, TM and Sejnowski, TJ and Tartakovsky, DM}, title = {Efficient models of polymerization applied to FtsZ ring assembly in Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4933-4938}, pmid = {29686085}, issn = {1091-6490}, support = {P41 GM103712/GM/NIGMS NIH HHS/United States ; R01 MH079076/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bacterial Proteins/*chemistry/metabolism ; Cytoskeletal Proteins/*chemistry/metabolism ; Escherichia coli/*chemistry/metabolism ; *Models, Biological ; *Models, Chemical ; *Protein Multimerization ; }, abstract = {High protein concentrations complicate modeling of polymer assembly kinetics by introducing structural complexity and a large variety of protein forms. We present a modeling approach that achieves orders of magnitude speed-up by replacing distributions of lengths and widths with their average counterparts and by introducing a hierarchical classification of species and reactions into sets. We have used this model to study FtsZ ring assembly in Escherichia coli The model's prediction of key features of the ring formation, such as time to reach the steady state, total concentration of FtsZ species in the ring, total concentration of monomers, and average dimensions of filaments and bundles, are all in agreement with the experimentally observed values. Besides validating our model against the in vivo observations, this study fills some knowledge gaps by proposing a specific structure of the ring, describing the influence of the total concentration in short and long kinetics processes, determining some characteristic mechanisms in polymer assembly regulation, and providing insights about the role of ZapA proteins, critical components for both positioning and stability of the ring.}, } @article {pmid29686084, year = {2018}, author = {Csiki-Sava, Z and Vremir, M and Meng, J and Brusatte, SL and Norell, MA}, title = {Dome-headed, small-brained island mammal from the Late Cretaceous of Romania.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4857-4862}, pmid = {29686084}, issn = {1091-6490}, mesh = {Animals ; *Body Size ; Brain/*anatomy & histology ; *Fossils ; Mammals/*anatomy & histology ; Romania ; Skull/*anatomy & histology ; }, abstract = {The island effect is a well-known evolutionary phenomenon, in which island-dwelling species isolated in a resource-limited environment often modify their size, anatomy, and behaviors compared with mainland relatives. This has been well documented in modern and Cenozoic mammals, but it remains unclear whether older, more primitive Mesozoic mammals responded in similar ways to island habitats. We describe a reasonably complete and well-preserved skeleton of a kogaionid, an enigmatic radiation of Cretaceous island-dwelling multituberculate mammals previously represented by fragmentary fossils. This skeleton, from the latest Cretaceous of Romania, belongs to a previously unreported genus and species that possesses several aberrant features, including an autapomorphically domed skull and one of the smallest brains relative to body size of any advanced mammaliaform, which nonetheless retains enlarged olfactory bulbs and paraflocculi for sensory processing. Drawing on parallels with more recent island mammals, we interpret these unusual neurosensory features as related to the island effect. This indicates that the ability to adapt to insular environments developed early in mammalian history, before the advent of therian mammals, and mammals with insular-related modifications were key components of well-known dwarfed dinosaur faunas. Furthermore, the specimen suggests that brain size reduction, in association with heightened sensory acuity but without marked body size change, is a novel expression of the island effect in mammals.}, } @article {pmid29686083, year = {2018}, author = {Regnault, C and Usal, M and Veyrenc, S and Couturier, K and Batandier, C and Bulteau, AL and Lejon, D and Sapin, A and Combourieu, B and Chetiveaux, M and Le May, C and Lafond, T and Raveton, M and Reynaud, S}, title = {Unexpected metabolic disorders induced by endocrine disruptors in Xenopus tropicalis provide new lead for understanding amphibian decline.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4416-E4425}, pmid = {29686083}, issn = {1091-6490}, mesh = {Animals ; Benzo(a)pyrene/*toxicity ; Chemical and Drug Induced Liver Injury/*metabolism ; *Extinction, Biological ; Female ; *Glucose Intolerance/chemically induced/metabolism ; Larva/metabolism ; Metamorphosis, Biological/drug effects ; Triclosan/*toxicity ; Xenopus/*metabolism ; }, abstract = {Despite numerous studies suggesting that amphibians are highly sensitive to endocrine disruptors (EDs), both their role in the decline of populations and the underlying mechanisms remain unclear. This study showed that frogs exposed throughout their life cycle to ED concentrations low enough to be considered safe for drinking water, developed a prediabetes phenotype and, more commonly, a metabolic syndrome. Female Xenopus tropicalis exposed from tadpole stage to benzo(a)pyrene or triclosan at concentrations of 50 ng⋅L-1 displayed glucose intolerance syndrome, liver steatosis, liver mitochondrial dysfunction, liver transcriptomic signature, and pancreatic insulin hypersecretion, all typical of a prediabetes state. This metabolic syndrome led to progeny whose metamorphosis was delayed and occurred while the individuals were both smaller and lighter, all factors that have been linked to reduced adult recruitment and likelihood of reproduction. We found that F1 animals did indeed have reduced reproductive success, demonstrating a lower fitness in ED-exposed Xenopus Moreover, after 1 year of depuration, Xenopus that had been exposed to benzo(a)pyrene still displayed hepatic disorders and a marked insulin secretory defect resulting in glucose intolerance. Our results demonstrate that amphibians are highly sensitive to EDs at concentrations well below the thresholds reported to induce stress in other vertebrates. This study introduces EDs as a possible key contributing factor to amphibian population decline through metabolism disruption. Overall, our results show that EDs cause metabolic disorders, which is in agreement with epidemiological studies suggesting that environmental EDs might be one of the principal causes of metabolic disease in humans.}, } @article {pmid29686082, year = {2018}, author = {Yeom, J and Gao, X and Groisman, EA}, title = {Reduction in adaptor amounts establishes degradation hierarchy among protease substrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4483-E4492}, pmid = {29686082}, issn = {1091-6490}, support = {R01 AI049561/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Base Sequence ; Carrier Proteins/genetics/*metabolism ; Escherichia coli/growth & development/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; *Proteolysis ; Salmonella/growth & development/*metabolism ; Sequence Homology ; Substrate Specificity ; }, abstract = {ATP-dependent proteases control critical cellular processes, including development, physiology, and virulence. A given protease may recognize a substrate directly via an unfoldase domain or subunit or indirectly via an adaptor that delivers the substrate to the unfoldase. We now report that cells achieve differential stability among substrates of a given protease by modulating adaptor amounts. We establish that the regulatory protein PhoP represses transcription of the gene specifying the ClpAP protease adaptor ClpS when the bacteria Salmonella enterica and Escherichia coli experience low cytoplasmic Mg2+ The resulting decrease in ClpS amounts diminishes proteolysis of several ClpSAP-dependent substrates, including the putrescine aminotransferase Oat, which heightens the formation of antibiotic persisters, and the transcriptional regulators UvrY and PhoP, which alter the expression of genes controlled by these proteins. By contrast, the decrease in ClpS amounts did not impact the abundance of the ClpSAP substrate FtsA, reflecting that FtsA binds to ClpS more tightly than to UvrY and PhoP. Our findings show how physiological conditions that reduce adaptor amounts modify the abundance of selected substrates of a given protease.}, } @article {pmid29686081, year = {2018}, author = {Mutz, DC}, title = {Status threat, not economic hardship, explains the 2016 presidential vote.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4330-E4339}, pmid = {29686081}, issn = {1091-6490}, mesh = {Humans ; *Industrial Development ; Internationality ; *Politics ; United States ; }, abstract = {This study evaluates evidence pertaining to popular narratives explaining the American public's support for Donald J. Trump in the 2016 presidential election. First, using unique representative probability samples of the American public, tracking the same individuals from 2012 to 2016, I examine the "left behind" thesis (that is, the theory that those who lost jobs or experienced stagnant wages due to the loss of manufacturing jobs punished the incumbent party for their economic misfortunes). Second, I consider the possibility that status threat felt by the dwindling proportion of traditionally high-status Americans (i.e., whites, Christians, and men) as well as by those who perceive America's global dominance as threatened combined to increase support for the candidate who emphasized reestablishing status hierarchies of the past. Results do not support an interpretation of the election based on pocketbook economic concerns. Instead, the shorter relative distance of people's own views from the Republican candidate on trade and China corresponded to greater mass support for Trump in 2016 relative to Mitt Romney in 2012. Candidate preferences in 2016 reflected increasing anxiety among high-status groups rather than complaints about past treatment among low-status groups. Both growing domestic racial diversity and globalization contributed to a sense that white Americans are under siege by these engines of change.}, } @article {pmid29686080, year = {2018}, author = {Lee, JK and Bangayan, NJ and Chai, T and Smith, BA and Pariva, TE and Yun, S and Vashisht, A and Zhang, Q and Park, JW and Corey, E and Huang, J and Graeber, TG and Wohlschlegel, J and Witte, ON}, title = {Systemic surfaceome profiling identifies target antigens for immune-based therapy in subtypes of advanced prostate cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4473-E4482}, pmid = {29686080}, issn = {1091-6490}, support = {K99 CA218731/CA/NCI NIH HHS/United States ; P01 CA168585/CA/NCI NIH HHS/United States ; P50 CA092131/CA/NCI NIH HHS/United States ; R01 CA220238/CA/NCI NIH HHS/United States ; }, mesh = {Antigens, Surface/*analysis/*immunology ; Carcinoembryonic Antigen/genetics/immunology/metabolism ; Carcinoma, Neuroendocrine/genetics/immunology/metabolism/*therapy ; Cell Differentiation ; Cells, Cultured ; GPI-Linked Proteins/genetics/immunology/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Immunotherapy ; Male ; Membrane Proteins/genetics/immunology/metabolism ; Neoplasm Proteins/genetics/immunology/metabolism ; Prostate/immunology/metabolism ; Prostatic Neoplasms/genetics/immunology/metabolism/*therapy ; Proteome/*analysis/immunology ; T-Lymphocytes/cytology/immunology/*transplantation ; *Transcriptome ; }, abstract = {Prostate cancer is a heterogeneous disease composed of divergent molecular and histologic subtypes, including prostate adenocarcinoma (PrAd) and neuroendocrine prostate cancer (NEPC). While PrAd is the major histology in prostate cancer, NEPC can evolve from PrAd as a mechanism of treatment resistance that involves a transition from an epithelial to a neurosecretory cancer phenotype. Cell surface markers are often associated with specific cell lineages and differentiation states in normal development and cancer. Here, we show that PrAd and NEPC can be broadly discriminated by cell-surface profiles based on the analysis of prostate cancer gene expression datasets. To overcome a dependence on predictions of human cell-surface genes and an assumed correlation between mRNA levels and protein expression, we integrated transcriptomic and cell-surface proteomic data generated from a panel of prostate cancer cell lines to nominate cell-surface markers associated with these cancer subtypes. FXYD3 and CEACAM5 were validated as cell-surface antigens enriched in PrAd and NEPC, respectively. Given the lack of effective treatments for NEPC, CEACAM5 appeared to be a promising target for cell-based immunotherapy. As a proof of concept, engineered chimeric antigen receptor T cells targeting CEACAM5 induced antigen-specific cytotoxicity in NEPC cell lines. Our findings demonstrate that the surfaceomes of PrAd and NEPC reflect unique cancer differentiation states and broadly represent vulnerabilities amenable to therapeutic targeting.}, } @article {pmid29686079, year = {2018}, author = {Muscente, AD and Prabhu, A and Zhong, H and Eleish, A and Meyer, MB and Fox, P and Hazen, RM and Knoll, AH}, title = {Quantifying ecological impacts of mass extinctions with network analysis of fossil communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5217-5222}, pmid = {29686079}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; Biological Evolution ; *Databases, Factual ; *Ecosystem ; *Extinction, Biological ; *Fossils ; Geology ; Invertebrates ; *Paleontology ; }, abstract = {Mass extinctions documented by the fossil record provide critical benchmarks for assessing changes through time in biodiversity and ecology. Efforts to compare biotic crises of the past and present, however, encounter difficulty because taxonomic and ecological changes are decoupled, and although various metrics exist for describing taxonomic turnover, no methods have yet been proposed to quantify the ecological impacts of extinction events. To address this issue, we apply a network-based approach to exploring the evolution of marine animal communities over the Phanerozoic Eon. Network analysis of fossil co-occurrence data enables us to identify nonrandom associations of interrelated paleocommunities. These associations, or evolutionary paleocommunities, dominated total diversity during successive intervals of relative community stasis. Community turnover occurred largely during mass extinctions and radiations, when ecological reorganization resulted in the decline of one association and the rise of another. Altogether, we identify five evolutionary paleocommunities at the generic and familial levels in addition to three ordinal associations that correspond to Sepkoski's Cambrian, Paleozoic, and Modern evolutionary faunas. In this context, we quantify magnitudes of ecological change by measuring shifts in the representation of evolutionary paleocommunities over geologic time. Our work shows that the Great Ordovician Biodiversification Event had the largest effect on ecology, followed in descending order by the Permian-Triassic, Cretaceous-Paleogene, Devonian, and Triassic-Jurassic mass extinctions. Despite its taxonomic severity, the Ordovician extinction did not strongly affect co-occurrences of taxa, affirming its limited ecological impact. Network paleoecology offers promising approaches to exploring ecological consequences of extinctions and radiations.}, } @article {pmid29686078, year = {2018}, author = {Price, N and Moyers, BT and Lopez, L and Lasky, JR and Monroe, JG and Mullen, JL and Oakley, CG and Lin, J and Ågren, J and Schrider, DR and Kern, AD and McKay, JK}, title = {Combining population genomics and fitness QTLs to identify the genetics of local adaptation in Arabidopsis thaliana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {5028-5033}, pmid = {29686078}, issn = {1091-6490}, support = {R01 GM078204/GM/NIGMS NIH HHS/United States ; R01 GM117241/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Arabidopsis/*genetics ; *Genome, Plant ; Italy ; *Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; Sweden ; }, abstract = {Evidence for adaptation to different climates in the model species Arabidopsis thaliana is seen in reciprocal transplant experiments, but the genetic basis of this adaptation remains poorly understood. Field-based quantitative trait locus (QTL) studies provide direct but low-resolution evidence for the genetic basis of local adaptation. Using high-resolution population genomic approaches, we examine local adaptation along previously identified genetic trade-off (GT) and conditionally neutral (CN) QTLs for fitness between locally adapted Italian and Swedish A. thaliana populations [Ågren J, et al. (2013) Proc Natl Acad Sci USA 110:21077-21082]. We find that genomic regions enriched in high FST SNPs colocalize with GT QTL peaks. Many of these high FST regions also colocalize with regions enriched for SNPs significantly correlated to climate in Eurasia and evidence of recent selective sweeps in Sweden. Examining unfolded site frequency spectra across genes containing high FST SNPs suggests GTs may be due to more recent adaptation in Sweden than Italy. Finally, we collapse a list of thousands of genes spanning GT QTLs to 42 genes that likely underlie the observed GTs and explore potential biological processes driving these trade-offs, from protein phosphorylation, to seed dormancy and longevity. Our analyses link population genomic analyses and field-based QTL studies of local adaptation, and emphasize that GTs play an important role in the process of local adaptation.}, } @article {pmid29686077, year = {2018}, author = {Doctrow, B}, title = {QnAs with Howard Y. Chang.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4805-4806}, pmid = {29686077}, issn = {1091-6490}, mesh = {Animals ; *Awards and Prizes ; History, 21st Century ; Humans ; Molecular Biology/*history ; Portraits as Topic ; *RNA, Long Noncoding ; }, } @article {pmid29686076, year = {2018}, author = {Perchat, N and Saaidi, PL and Darii, E and Pellé, C and Petit, JL and Besnard-Gonnet, M and de Berardinis, V and Dupont, M and Gimbernat, A and Salanoubat, M and Fischer, C and Perret, A}, title = {Elucidation of the trigonelline degradation pathway reveals previously undescribed enzymes and metabolites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4358-E4367}, pmid = {29686076}, issn = {1091-6490}, mesh = {*Acinetobacter/enzymology/genetics ; Alkaloids/*metabolism ; Chromatography, Liquid ; *Genome, Bacterial ; Mass Spectrometry ; *Molecular Sequence Annotation ; *Multigene Family ; }, abstract = {Trigonelline (TG; N-methylnicotinate) is a ubiquitous osmolyte. Although it is known that it can be degraded, the enzymes and metabolites have not been described so far. In this work, we challenged the laboratory model soil-borne, gram-negative bacterium Acinetobacter baylyi ADP1 (ADP1) for its ability to grow on TG and we identified a cluster of catabolic, transporter, and regulatory genes. We dissected the pathway to the level of enzymes and metabolites, and proceeded to in vitro reconstruction of the complete pathway by six purified proteins. The four enzymatic steps that lead from TG to methylamine and succinate are described, and the structures of previously undescribed metabolites are provided. Unlike many aromatic compounds that undergo hydroxylation prior to ring cleavage, the first step of TG catabolism proceeds through direct cleavage of the C5-C6 bound, catalyzed by a flavin-dependent, two-component oxygenase, which yields (Z)-2-((N-methylformamido)methylene)-5-hydroxy-butyrolactone (MFMB). MFMB is then oxidized into (E)-2-((N-methylformamido) methylene) succinate (MFMS), which is split up by a hydrolase into carbon dioxide, methylamine, formic acid, and succinate semialdehyde (SSA). SSA eventually fuels up the TCA by means of an SSA dehydrogenase, assisted by a Conserved Hypothetical Protein. The cluster is conserved across marine, soil, and plant-associated bacteria. This emphasizes the role of TG as a ubiquitous nutrient for which an efficient microbial catabolic toolbox is available.}, } @article {pmid29686075, year = {2018}, author = {Bänfer, S and Schneider, D and Dewes, J and Strauss, MT and Freibert, SA and Heimerl, T and Maier, UG and Elsässer, HP and Jungmann, R and Jacob, R}, title = {Molecular mechanism to recruit galectin-3 into multivesicular bodies for polarized exosomal secretion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4396-E4405}, pmid = {29686075}, issn = {1091-6490}, mesh = {Animals ; DNA-Binding Proteins/*metabolism ; Dogs ; Endosomal Sorting Complexes Required for Transport/*metabolism ; Endosomes/*metabolism/ultrastructure ; Exosomes/*metabolism/ultrastructure ; Galectin 3/*metabolism ; Madin Darby Canine Kidney Cells ; Microscopy, Electron ; Multivesicular Bodies/*metabolism/ultrastructure ; Transcription Factors/*metabolism ; Vacuolar Proton-Translocating ATPases/*metabolism ; }, abstract = {The beta-galactoside binding lectin galectin-3 (Gal3) is found intracellularly and in the extracellular space. Secretion of this lectin is mediated independently of the secretory pathway by a not yet defined nonclassical mechanism. Here, we found Gal3 in the lumen of exosomes. Superresolution and electron microscopy studies visualized Gal3 recruitment and sorting into intraluminal vesicles. Exosomal Gal3 release depends on the endosomal sorting complex required for transport I (ESCRT-I) component Tsg101 and functional Vps4a. Either Tsg101 knockdown or expression of dominant-negative Vps4aE228Q causes an intracellular Gal3 accumulation at multivesicular body formation sites. In addition, we identified a highly conserved tetrapeptide P(S/T)AP motif in the amino terminus of Gal3 that mediates a direct interaction with Tsg101. Mutation of the P(S/T)AP motif results in a loss of interaction and a dramatic decrease in exosomal Gal3 secretion. We conclude that Gal3 is a member of endogenous non-ESCRT proteins which are P(S/T)AP tagged for exosomal release.}, } @article {pmid29686074, year = {2018}, author = {Maxwell, SJ and Hopley, PJ and Upchurch, P and Soligo, C}, title = {Sporadic sampling, not climatic forcing, drives observed early hominin diversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4891-4896}, pmid = {29686074}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; *Climate Change ; *Fossils ; Hominidae/*classification/*physiology ; }, abstract = {The role of climate change in the origin and diversification of early hominins is hotly debated. Most accounts of early hominin evolution link observed fluctuations in species diversity to directional shifts in climate or periods of intense climatic instability. None of these hypotheses, however, have tested whether observed diversity patterns are distorted by variation in the quality of the hominin fossil record. Here, we present a detailed examination of early hominin diversity dynamics, including both taxic and phylogenetically corrected diversity estimates. Unlike past studies, we compare these estimates to sampling metrics for rock availability (hominin-, primate-, and mammal-bearing formations) and collection effort, to assess the geological and anthropogenic controls on the sampling of the early hominin fossil record. Taxic diversity, primate-bearing formations, and collection effort show strong positive correlations, demonstrating that observed patterns of early hominin taxic diversity can be explained by temporal heterogeneity in fossil sampling rather than genuine evolutionary processes. Peak taxic diversity at 1.9 million years ago (Ma) is a sampling artifact, reflecting merely maximal rock availability and collection effort. In contrast, phylogenetic diversity estimates imply peak diversity at 2.4 Ma and show little relation to sampling metrics. We find that apparent relationships between early hominin diversity and indicators of climatic instability are, in fact, driven largely by variation in suitable rock exposure and collection effort. Our results suggest that significant improvements in the quality of the fossil record are required before the role of climate in hominin evolution can be reliably determined.}, } @article {pmid29686073, year = {2018}, author = {Meng, D and Li, HQ and Deisseroth, K and Leutgeb, S and Spitzer, NC}, title = {Neuronal activity regulates neurotransmitter switching in the adult brain following light-induced stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5064-5071}, pmid = {29686073}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Brain/*metabolism/pathology/radiation effects ; Cells, Cultured ; Corticotropin-Releasing Hormone ; Dopamine/*metabolism ; Dopaminergic Neurons/cytology/*physiology ; Hypothalamus/metabolism/pathology/radiation effects ; *Light ; Male ; Neurotransmitter Agents/*metabolism/radiation effects ; Paraventricular Hypothalamic Nucleus/metabolism/pathology/radiation effects ; Rats ; Rats, Long-Evans ; Receptors, Dopamine/metabolism ; *Stress, Physiological ; Vesicular Glutamate Transport Protein 2/metabolism ; }, abstract = {Neurotransmitter switching in the adult mammalian brain occurs following photoperiod-induced stress, but the mechanism of regulation is unknown. Here, we demonstrate that elevated activity of dopaminergic neurons in the paraventricular nucleus of the hypothalamus (PaVN) in the adult rat is required for the loss of dopamine expression after long-day photoperiod exposure. The transmitter switch occurs exclusively in PaVN dopaminergic neurons that coexpress vesicular glutamate transporter 2 (VGLUT2), is accompanied by a loss of dopamine type 2 receptors (D2Rs) on corticotrophin-releasing factor (CRF) neurons, and can lead to increased release of CRF. Suppressing activity of all PaVN glutamatergic neurons decreases the number of inhibitory PaVN dopaminergic neurons, indicating homeostatic regulation of transmitter expression in the PaVN.}, } @article {pmid29686072, year = {2018}, author = {Chiang, FK and Wallis, JD}, title = {Spatiotemporal encoding of search strategies by prefrontal neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {5010-5015}, pmid = {29686072}, issn = {1091-6490}, support = {R01 MH097990/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Appetitive Behavior/*physiology ; Macaca mulatta ; Male ; Memory, Short-Term/*physiology ; Neurons/cytology/*physiology ; Prefrontal Cortex/cytology/*physiology ; }, abstract = {Working memory is capacity-limited. In everyday life we rarely notice this limitation, in part because we develop behavioral strategies that help mitigate the capacity limitation. How behavioral strategies are mediated at the neural level is unclear, but a likely locus is lateral prefrontal cortex (LPFC). Neurons in LPFC play a prominent role in working memory and have been shown to encode behavioral strategies. To examine the role of LPFC in overcoming working-memory limitations, we recorded the activity of LPFC neurons in animals trained to perform a serial self-ordered search task. This task measured the ability to prospectively plan the selection of unchosen spatial search targets while retrospectively tracking which targets were previously visited. We found that individual LPFC neurons encoded the spatial location of the current search target but also encoded the spatial location of targets up to several steps away in the search sequence. Neurons were more likely to encode prospective than retrospective targets. When subjects used a behavioral strategy of stereotyped target selection, mitigating the working-memory requirements of the task, not only did the number of selection errors decrease but there was a significant reduction in the strength of spatial encoding in LFPC. These results show that LPFC neurons have spatiotemporal mnemonic fields, in that their firing rates are modulated both by the spatial location of future selection behaviors and the temporal organization of that behavior. Furthermore, the strength of this tuning can be dynamically modulated by the demands of the task.}, } @article {pmid29686071, year = {2018}, author = {Bauer, M and Cahlíková, J and Chytilová, J and Želinský, T}, title = {Social contagion of ethnic hostility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4881-4886}, pmid = {29686071}, issn = {1091-6490}, mesh = {Adolescent ; *Ethnic Violence ; Female ; Humans ; Male ; *Roma ; Slovakia ; *Social Behavior ; }, abstract = {Interethnic conflicts often escalate rapidly. Why does the behavior of masses easily change from cooperation to aggression? This paper provides an experimental test of whether ethnic hostility is contagious. Using incentivized tasks, we measured willingness to sacrifice one's own resources to harm others among adolescents from a region with a history of animosities toward the Roma people, the largest ethnic minority in Europe. To identify the influence of peers, subjects made choices after observing either destructive or peaceful behavior of peers in the same task. We found that susceptibility to follow destructive behavior more than doubled when harm was targeted against Roma rather than against coethnics. When peers were peaceful, subjects did not discriminate. We observed very similar patterns in a norms-elicitation experiment: destructive behavior toward Roma was not generally rated as more socially appropriate than when directed at coethnics, but the ratings were more sensitive to social contexts. The findings may illuminate why ethnic hostilities can spread quickly, even in societies with few visible signs of interethnic hatred.}, } @article {pmid29686070, year = {2018}, author = {Gilpin, W}, title = {Cryptographic hashing using chaotic hydrodynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4869-4874}, pmid = {29686070}, issn = {1091-6490}, abstract = {Fluids may store and manipulate information, enabling complex applications ranging from digital logic gates to algorithmic self-assembly. While controllable hydrodynamic chaos has previously been observed in viscous fluids and harnessed for efficient mixing, its application to the manipulation of digital information has been sparsely investigated. We show that chaotic stirring of a viscous fluid naturally produces a characteristic signature of the stirring process in the arrangement of particles in the fluid, and that this signature directly satisfies the requirements for a cryptographic hash function. This includes strong divergence between similar stirring protocols' hashes and avoidance of collisions (identical hashes from distinct stirs), which are facilitated by noninvertibility and a broad chaotic attractor that samples many points in the fluid domain. The hashing ability of the chaotic fluidic map implicates several unexpected mechanisms, including incomplete mixing at short time scales that produces a hyperuniform hash distribution. We investigate the dynamics of hashing using interparticle winding statistics, and find that hashing starts with large-scale winding of kinetically disjoint regions of the chaotic attractor, which gradually gives way to smaller scale braiding of single-particle trajectories. In addition to providing a physically motivated approach to implementing and analyzing deterministic chaotic maps for cryptographic applications, we anticipate that our approach has applications in microfluidic proof-of-work systems and characterizing large-scale turbulent flows from sparse tracer data.}, } @article {pmid29686069, year = {2018}, author = {Ilyaskina, OS and Lemoine, H and Bünemann, M}, title = {Lifetime of muscarinic receptor-G-protein complexes determines coupling efficiency and G-protein subtype selectivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {5016-5021}, pmid = {29686069}, issn = {1091-6490}, mesh = {*Fluorescence Resonance Energy Transfer ; GTP-Binding Proteins/genetics/*metabolism ; HEK293 Cells ; Humans ; Multiprotein Complexes/genetics/*metabolism ; Receptor, Muscarinic M3/genetics/*metabolism ; }, abstract = {G-protein-coupled receptors (GPCRs) are essential for the detection of extracellular stimuli by cells and transfer the encoded information via the activation of functionally distinct subsets of heterotrimeric G proteins into intracellular signals. Despite enormous achievements toward understanding GPCR structures, major aspects of the GPCR-G-protein selectivity mechanism remain unresolved. As this can be attributed to the lack of suitable and broadly applicable assays, we set out to develop a quantitative FRET-based assay to study kinetics and affinities of G protein binding to activated GPCRs in membranes of permeabilized cells in the absence of nucleotides. We measured the association and dissociation kinetics of agonist-induced binding of Gi/o, Gq/11, Gs, and G12/13 proteins to muscarinic M1, M2, and M3 receptors in the absence of nucleotides between fluorescently labeled G proteins and receptors expressed in mammalian cells. Our results show a strong quantitative correlation between not the on-rates of G-protein-M3-R interactions but rather the affinities of Gq and Go proteins to M3-Rs, their GPCR-G-protein lifetime and their coupling efficiencies determined in intact cells, suggesting that the G-protein subtype-specific affinity to the activated receptor in the absence of nucleotides is, in fact, a major determinant of the coupling efficiency. Our broadly applicable FRET-based assay represents a fast and reliable method to quantify the intrinsic affinity and relative coupling selectivity of GPCRs toward all G-protein subtypes.}, } @article {pmid29686068, year = {2018}, author = {Cantsilieris, S and Nelson, BJ and Huddleston, J and Baker, C and Harshman, L and Penewit, K and Munson, KM and Sorensen, M and Welch, AE and Dang, V and Grassmann, F and Richardson, AJ and Guymer, RH and Graves-Lindsay, TA and Wilson, RK and Weber, BHF and Baird, PN and Allikmets, R and Eichler, EE}, title = {Recurrent structural variation, clustered sites of selection, and disease risk for the complement factor H (CFH) gene family.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4433-E4442}, pmid = {29686068}, issn = {1091-6490}, support = {P30 EY019007/EY/NEI NIH HHS/United States ; R01 EY013435/EY/NEI NIH HHS/United States ; R01 HG002385/HG/NHGRI NIH HHS/United States ; U41 HG007635/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Complement Factor H/genetics ; *Evolution, Molecular ; Exons ; Genetic Predisposition to Disease ; Genotype ; Haplotypes ; Humans ; Macular Degeneration/*genetics/*pathology ; Multigene Family ; *Mutation ; Phenotype ; *Polymorphism, Single Nucleotide ; Primates ; Risk Factors ; *Selection, Genetic ; }, abstract = {Structural variation and single-nucleotide variation of the complement factor H (CFH) gene family underlie several complex genetic diseases, including age-related macular degeneration (AMD) and atypical hemolytic uremic syndrome (AHUS). To understand its diversity and evolution, we performed high-quality sequencing of this ∼360-kbp locus in six primate lineages, including multiple human haplotypes. Comparative sequence analyses reveal two distinct periods of gene duplication leading to the emergence of four CFH-related (CFHR) gene paralogs (CFHR2 and CFHR4 ∼25-35 Mya and CFHR1 and CFHR3 ∼7-13 Mya). Remarkably, all evolutionary breakpoints share a common ∼4.8-kbp segment corresponding to an ancestral CFHR gene promoter that has expanded independently throughout primate evolution. This segment is recurrently reused and juxtaposed with a donor duplication containing exons 8 and 9 from ancestral CFH, creating four CFHR fusion genes that include lineage-specific members of the gene family. Combined analysis of >5,000 AMD cases and controls identifies a significant burden of a rare missense mutation that clusters at the N terminus of CFH [P = 5.81 × 10-8, odds ratio (OR) = 9.8 (3.67-Infinity)]. A bipolar clustering pattern of rare nonsynonymous mutations in patients with AMD (P < 10-3) and AHUS (P = 0.0079) maps to functional domains that show evidence of positive selection during primate evolution. Our structural variation analysis in >2,400 individuals reveals five recurrent rearrangement breakpoints that show variable frequency among AMD cases and controls. These data suggest a dynamic and recurrent pattern of mutation critical to the emergence of new CFHR genes but also in the predisposition to complex human genetic disease phenotypes.}, } @article {pmid29686067, year = {2018}, author = {Rabbani, HS and Or, D and Liu, Y and Lai, CY and Lu, NB and Datta, SS and Stone, HA and Shokri, N}, title = {Suppressing viscous fingering in structured porous media.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4833-4838}, pmid = {29686067}, issn = {1091-6490}, abstract = {Finger-like protrusions that form along fluid-fluid displacement fronts in porous media are often excited by hydrodynamic instability when low-viscosity fluids displace high-viscosity resident fluids. Such interfacial instabilities are undesirable in many natural and engineered displacement processes. We report a phenomenon whereby gradual and monotonic variation of pore sizes along the front path suppresses viscous fingering during immiscible displacement, that seemingly contradicts conventional expectation of enhanced instability with pore size variability. Experiments and pore-scale numerical simulations were combined with an analytical model for the characteristics of displacement front morphology as a function of the pore size gradient. Our results suggest that the gradual reduction of pore sizes act to restrain viscous fingering for a predictable range of flow conditions (as anticipated by gradient percolation theory). The study provides insights into ways for suppressing unwanted interfacial instabilities in porous media, and provides design principles for new engineered porous media such as exchange columns, fabric, paper, and membranes with respect to their desired immiscible displacement behavior.}, } @article {pmid29686066, year = {2018}, author = {Gabrielsen, P}, title = {QnAs with Nicholas C. Spitzer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5047-5048}, pmid = {29686066}, issn = {1091-6490}, mesh = {Animals ; Humans ; Neurons/*physiology ; Neurotransmitter Agents/*metabolism ; Synapses/*physiology ; Synaptic Transmission/*physiology ; }, } @article {pmid29686065, year = {2018}, author = {Lewin, HA and Robinson, GE and Kress, WJ and Baker, WJ and Coddington, J and Crandall, KA and Durbin, R and Edwards, SV and Forest, F and Gilbert, MTP and Goldstein, MM and Grigoriev, IV and Hackett, KJ and Haussler, D and Jarvis, ED and Johnson, WE and Patrinos, A and Richards, S and Castilla-Rubio, JC and van Sluys, MA and Soltis, PS and Xu, X and Yang, H and Zhang, G}, title = {Earth BioGenome Project: Sequencing life for the future of life.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4325-4333}, pmid = {29686065}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Biodiversity ; Earth (Planet) ; *Endangered Species ; *Genome ; *High-Throughput Nucleotide Sequencing ; }, abstract = {Increasing our understanding of Earth's biodiversity and responsibly stewarding its resources are among the most crucial scientific and social challenges of the new millennium. These challenges require fundamental new knowledge of the organization, evolution, functions, and interactions among millions of the planet's organisms. Herein, we present a perspective on the Earth BioGenome Project (EBP), a moonshot for biology that aims to sequence, catalog, and characterize the genomes of all of Earth's eukaryotic biodiversity over a period of 10 years. The outcomes of the EBP will inform a broad range of major issues facing humanity, such as the impact of climate change on biodiversity, the conservation of endangered species and ecosystems, and the preservation and enhancement of ecosystem services. We describe hurdles that the project faces, including data-sharing policies that ensure a permanent, freely available resource for future scientific discovery while respecting access and benefit sharing guidelines of the Nagoya Protocol. We also describe scientific and organizational challenges in executing such an ambitious project, and the structure proposed to achieve the project's goals. The far-reaching potential benefits of creating an open digital repository of genomic information for life on Earth can be realized only by a coordinated international effort.}, } @article {pmid29686064, year = {2018}, author = {Baraniak, I and Kropff, B and Ambrose, L and McIntosh, M and McLean, GR and Pichon, S and Atkinson, C and Milne, RSB and Mach, M and Griffiths, PD and Reeves, MB}, title = {Protection from cytomegalovirus viremia following glycoprotein B vaccination is not dependent on neutralizing antibodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {24}, pages = {6273-6278}, pmid = {29686064}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 AI051355/AI/NIAID NIH HHS/United States ; WT/204870/Z/16/Z//Wellcome Trust/United Kingdom ; G:0900466//Medical Research Council/United Kingdom ; }, mesh = {Adjuvants, Immunologic/pharmacology ; Antibodies, Neutralizing/*immunology ; Antibodies, Viral/*immunology ; Cytomegalovirus/*immunology ; Cytomegalovirus Infections/*immunology ; Cytomegalovirus Vaccines/*immunology ; Humans ; Vaccination/methods ; Viral Envelope Proteins/*immunology ; Viral Load/immunology ; Viremia/*immunology ; }, abstract = {Human cytomegalovirus (HCMV) is an important pathogen in transplant patients and in congenital infection. Previously, we demonstrated that vaccination with a recombinant viral glycoprotein B (gB)/MF59 adjuvant formulation before solid organ transplant reduced viral load parameters post transplant. Reduced posttransplant viremia was directly correlated with antibody titers against gB consistent with a humoral response against gB being important. Here we show that sera from the vaccinated seronegative patients displayed little evidence of a neutralizing antibody response against cell-free HCMV in vitro. Additionally, sera from seronegative vaccine recipients had minimal effect on the replication of a strain of HCMV engineered to be cell-associated in a viral spread assay. Furthermore, although natural infection can induce antibody-dependent cellular cytotoxicity (ADCC) responses, serological analysis of seronegative vaccinees again presented no evidence of a substantial ADCC-promoting antibody response being generated de novo. Finally, analyses for responses against major antigenic domains of gB following vaccination were variable, and their pattern was distinct compared with natural infection. Taken together, these data argue that the protective effect elicited by the gB vaccine is via a mechanism of action in seronegative vaccinees that cannot be explained by neutralization or the induction of ADCC. More generally, these data, which are derived from a human challenge model that demonstrated that the gB vaccine is protective, highlight the need for more sophisticated analyses of new HCMV vaccines over and above the quantification of an ability to induce potent neutralizing antibody responses in vitro.}, } @article {pmid29686063, year = {2018}, author = {Sanchez, DL and Johnson, N and McCoy, ST and Turner, PA and Mach, KJ}, title = {Near-term deployment of carbon capture and sequestration from biorefineries in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4875-4880}, doi = {10.1073/pnas.1719695115}, pmid = {29686063}, issn = {1091-6490}, abstract = {Capture and permanent geologic sequestration of biogenic CO2 emissions may provide critical flexibility in ambitious climate change mitigation. However, most bioenergy with carbon capture and sequestration (BECCS) technologies are technically immature or commercially unavailable. Here, we evaluate low-cost, commercially ready CO2 capture opportunities for existing ethanol biorefineries in the United States. The analysis combines process engineering, spatial optimization, and lifecycle assessment to consider the technical, economic, and institutional feasibility of near-term carbon capture and sequestration (CCS). Our modeling framework evaluates least cost source-sink relationships and aggregation opportunities for pipeline transport, which can cost-effectively transport small CO2 volumes to suitable sequestration sites; 216 existing US biorefineries emit 45 Mt CO2 annually from fermentation, of which 60% could be captured and compressed for pipeline transport for under $25/tCO2 A sequestration credit, analogous to existing CCS tax credits, of $60/tCO2 could incent 30 Mt of sequestration and 6,900 km of pipeline infrastructure across the United States. Similarly, a carbon abatement credit, analogous to existing tradeable CO2 credits, of $90/tCO2 can incent 38 Mt of abatement. Aggregation of CO2 sources enables cost-effective long-distance pipeline transport to distant sequestration sites. Financial incentives under the low-carbon fuel standard in California and recent revisions to existing federal tax credits suggest a substantial near-term opportunity to permanently sequester biogenic CO2 This financial opportunity could catalyze the growth of carbon capture, transport, and sequestration; improve the lifecycle impacts of conventional biofuels; support development of carbon-negative fuels; and help fulfill the mandates of low-carbon fuel policies across the United States.}, } @article {pmid29686062, year = {2018}, author = {Dunn, HA and Patil, DN and Cao, Y and Orlandi, C and Martemyanov, KA}, title = {Synaptic adhesion protein ELFN1 is a selective allosteric modulator of group III metabotropic glutamate receptors in trans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {5022-5027}, pmid = {29686062}, issn = {1091-6490}, support = {K02 DA026405/DA/NIDA NIH HHS/United States ; R01 EY018139/EY/NEI NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Allosteric Regulation/physiology ; Binding Sites ; Cyclic AMP/genetics/*metabolism ; HEK293 Cells ; Humans ; Mutagenesis, Site-Directed ; Nerve Tissue Proteins/genetics/*metabolism ; Receptors, Metabotropic Glutamate/genetics/*metabolism ; *Second Messenger Systems ; }, abstract = {Functional characterization of the GPCR interactome has been focused predominantly on intracellular interactions, yet GPCRs are increasingly found in complex with extracellular proteins. Extracellular leucine-rich repeat fibronectin type III domain containing 1 (ELFN1) was recently reported to physically anchor mGluR6 and mGluR7 across retinal and hippocampal synapses, respectively; however, the consequence of transsynaptic interactions on properties and pharmacology of these receptors are unknown. In the current study, we explore the effects of ELFN1 on mGluR signaling and pharmacology. First, we established the binding specificity of ELFN1 and found it to be recruited selectively to all group III mGluRs (mGluR4, mGluR6, mGluR7, and mGluR8), but not other mGluR species. Using site-directed mutagenesis we mapped binding determinants of this interaction to two distinct sites on the ELFN1 ectodomain. To evaluate functional aspects of the interaction, we developed a transcellular signaling assay in reconstituted HEK293 cells which monitors changes in mGluR activity in one cell following its exposure to separate ELFN1-containing cells. Using this platform, we found that ELFN1 acts as an allosteric modulator of class III mGluR activity in suppressing cAMP accumulation: altering both agonist-induced and constitutive receptor activity. Using bioluminescence resonance energy transfer-based real-time kinetic assays, we established that ELFN1 alters the ability of mGluRs to activate G proteins. Our findings demonstrate that core properties of class III mGluRs can be altered via extracellular interactions with ELFN1 which serves as a transsynaptic allosteric modulator for these receptors. Furthermore, our unique assay platform opens avenues for exploring transcellular/transsynaptic pharmacology of other GPCR transcomplexes.}, } @article {pmid29686061, year = {2018}, author = {Qin, XY and Suzuki, H and Honda, M and Okada, H and Kaneko, S and Inoue, I and Ebisui, E and Hashimoto, K and Carninci, P and Kanki, K and Tatsukawa, H and Ishibashi, N and Masaki, T and Matsuura, T and Kagechika, H and Toriguchi, K and Hatano, E and Shirakami, Y and Shiota, G and Shimizu, M and Moriwaki, H and Kojima, S}, title = {Prevention of hepatocellular carcinoma by targeting MYCN-positive liver cancer stem cells with acyclic retinoid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4969-4974}, pmid = {29686061}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*pharmacology ; Carcinoma, Hepatocellular/diagnosis/metabolism/pathology/*prevention & control ; Epithelial Cell Adhesion Molecule/metabolism ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Liver Neoplasms/diagnosis/metabolism/pathology/*prevention & control ; N-Myc Proto-Oncogene Protein/*biosynthesis ; Neoplasm Metastasis ; Neoplastic Stem Cells/*metabolism/pathology ; Prognosis ; Tretinoin/*analogs & derivatives/pharmacology ; Wnt Signaling Pathway/*drug effects ; }, abstract = {Hepatocellular carcinoma (HCC) is a highly lethal cancer that has a high rate of recurrence, in part because of cancer stem cell (CSC)-dependent field cancerization. Acyclic retinoid (ACR) is a synthetic vitamin A-like compound capable of preventing the recurrence of HCC. Here, we performed a genome-wide transcriptome screen and showed that ACR selectively suppressed the expression of MYCN, a member of the MYC family of basic helix-loop-helix-zipper transcription factors, in HCC cell cultures, animal models, and liver biopsies obtained from HCC patients. MYCN expression in human HCC was correlated positively with both CSC and Wnt/β-catenin signaling markers but negatively with mature hepatocyte markers. Functional analysis showed repressed cell-cycle progression, proliferation, and colony formation, activated caspase-8, and induced cell death in HCC cells following silencing of MYCN expression. High-content single-cell imaging analysis and flow cytometric analysis identified a MYCN+ CSC subpopulation in the heterogeneous HCC cell cultures and showed that these cells were selectively killed by ACR. Particularly, EpCAM+ cells isolated using a cell-sorting system showed increased MYCN expression and sensitivity to ACR compared with EpCAM- cells. In a long-term (>10 y) follow-up study of 102 patients with HCC, MYCN was expressed at higher levels in the HCC tumor region than in nontumor regions, and there was a positive correlation between MYCN expression and recurrence of de novo HCC but not metastatic HCC after curative treatment. In summary, these results suggest that MYCN serves as a prognostic biomarker and therapeutic target of ACR for liver CSCs in de novo HCC.}, } @article {pmid29686060, year = {2018}, author = {Kim, Y and Yoo, JY and Lee, TJ and Liu, J and Yu, J and Caligiuri, MA and Kaur, B and Friedman, A}, title = {Complex role of NK cells in regulation of oncolytic virus-bortezomib therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4927-4932}, pmid = {29686060}, issn = {1091-6490}, support = {R01 CA150153/CA/NCI NIH HHS/United States ; R01 NS064607/NS/NINDS NIH HHS/United States ; R01 NS106170/NS/NINDS NIH HHS/United States ; P30 NS045758/NS/NINDS NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; P01 CA163205/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bortezomib/*therapeutic use ; Cell Line, Tumor ; Cercopithecus aethiops ; *Hematologic Neoplasms/immunology/pathology/therapy ; Humans ; Killer Cells, Natural/*immunology/pathology ; *Models, Immunological ; *Oncolytic Virotherapy ; *Tumor Microenvironment/drug effects/immunology ; Vero Cells ; }, abstract = {In the present work, we investigated the role of natural killer (NK) cells in combination therapy with oncolytic virus (OV) and bortezomib, a proteasome inhibitor. NK cells display rapid and potent immunity to metastatic and hematological cancers, and they overcome immunosuppressive effects of tumor microenvironment. We developed a mathematical model to address the question of how the density of NK cells affects the growth of the tumor. We found that the antitumor efficacy increases when the endogenous NKs are depleted and also when exogenous NK cells are injected into the tumor. These predictions were validated by our in vivo and in vitro experiments.}, } @article {pmid29686059, year = {2018}, author = {Saleem-Batcha, R and Stull, F and Sanders, JN and Moore, BS and Palfey, BA and Houk, KN and Teufel, R}, title = {Enzymatic control of dioxygen binding and functionalization of the flavin cofactor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4909-4914}, pmid = {29686059}, issn = {1091-6490}, support = {F32 GM122218/GM/NIGMS NIH HHS/United States ; R01 AI047818/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry ; Catalysis ; Coenzymes/*chemistry ; Crystallography, X-Ray ; Dinitrocresols/*chemistry ; Mixed Function Oxygenases/*chemistry ; *Molecular Docking Simulation ; Oxidation-Reduction ; Oxygen/*chemistry ; Quantum Theory ; }, abstract = {The reactions of enzymes and cofactors with gaseous molecules such as dioxygen (O2) are challenging to study and remain among the most contentious subjects in biochemistry. To date, it is largely enigmatic how enzymes control and fine-tune their reactions with O2, as exemplified by the ubiquitous flavin-dependent enzymes that commonly facilitate redox chemistry such as the oxygenation of organic substrates. Here we employ O2-pressurized X-ray crystallography and quantum mechanical calculations to reveal how the precise positioning of O2 within a flavoenzyme's active site enables the regiospecific formation of a covalent flavin-oxygen adduct and oxygenating species (i.e., the flavin-N5-oxide) by mimicking a critical transition state. This study unambiguously demonstrates how enzymes may control the O2 functionalization of an organic cofactor as prerequisite for oxidative catalysis. Our work thus illustrates how O2 reactivity can be harnessed in an enzymatic environment and provides crucial knowledge for future rational design of O2-reactive enzymes.}, } @article {pmid29686058, year = {2018}, author = {Perrella, G and Davidson, MLH and O'Donnell, L and Nastase, AM and Herzyk, P and Breton, G and Pruneda-Paz, JL and Kay, SA and Chory, J and Kaiserli, E}, title = {ZINC-FINGER interactions mediate transcriptional regulation of hypocotyl growth in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4503-E4511}, pmid = {29686058}, issn = {1091-6490}, support = {R01 GM050006/GM/NIGMS NIH HHS/United States ; R01 GM052413/GM/NIGMS NIH HHS/United States ; R01 GM067837/GM/NIGMS NIH HHS/United States ; R37 GM067837/GM/NIGMS NIH HHS/United States ; BB/M023079/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/genetics/*growth & development ; Arabidopsis Proteins/genetics/*metabolism ; Cell Nucleus/genetics/metabolism ; *Gene Expression Regulation, Plant ; Hypocotyl/genetics/*growth & development ; Photoperiod ; *Promoter Regions, Genetic ; Trans-Activators/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic ; Zinc Fingers ; }, abstract = {Integration of environmental signals and interactions among photoreceptors and transcriptional regulators is key in shaping plant development. TANDEM ZINC-FINGER PLUS3 (TZP) is an integrator of light and photoperiodic signaling that promotes flowering in Arabidopsis thaliana Here we elucidate the molecular role of TZP as a positive regulator of hypocotyl elongation. We identify an interacting partner for TZP, the transcription factor ZINC-FINGER HOMEODOMAIN 10 (ZFHD10), and characterize its function in coregulating the expression of blue-light-dependent transcriptional regulators and growth-promoting genes. By employing a genome-wide approach, we reveal that ZFHD10 and TZP coassociate with promoter targets enriched in light-regulated elements. Furthermore, using a targeted approach, we show that ZFHD10 recruits TZP to the promoters of key coregulated genes. Our findings not only unveil the mechanism of TZP action in promoting hypocotyl elongation at the transcriptional level but also assign a function to an uncharacterized member of the ZFHD transcription factor family in promoting plant growth.}, } @article {pmid29685980, year = {2018}, author = {Rathi, P and Maurer, S and Summerer, D}, title = {Selective recognition of N4-methylcytosine in DNA by engineered transcription-activator-like effectors.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685980}, issn = {1471-2970}, abstract = {The epigenetic DNA nucleobases 5-methylcytosine (5mC) and N4-methylcytosine (4mC) coexist in bacterial genomes and have important functions in host defence and transcription regulation. To better understand the individual biological roles of both methylated nucleobases, analytical strategies for distinguishing unmodified cytosine (C) from 4mC and 5mC are required. Transcription-activator-like effectors (TALEs) are programmable DNA-binding repeat proteins, which can be re-engineered for the direct detection of epigenetic nucleobases in user-defined DNA sequences. We here report the natural, cytosine-binding TALE repeat to not strongly differentiate between 5mC and 4mC. To engineer repeats with selectivity in the context of C, 5mC and 4mC, we developed a homogeneous fluorescence assay and screened a library of size-reduced TALE repeats for binding to all three nucleobases. This provided insights into the requirements of size-reduced TALE repeats for 4mC binding and revealed a single mutant repeat as a selective binder of 4mC. Employment of a TALE with this repeat in affinity enrichment enabled the isolation of a user-defined DNA sequence containing a single 4mC but not C or 5mC from the background of a bacterial genome. Comparative enrichments with TALEs bearing this or the natural C-binding repeat provides an approach for the complete, programmable decoding of all cytosine nucleobases found in bacterial genomes.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685979, year = {2018}, author = {Geel, TM and Ruiters, MHJ and Cool, RH and Halby, L and Voshart, DC and Andrade Ruiz, L and Niezen-Koning, KE and Arimondo, PB and Rots, MG}, title = {The past and presence of gene targeting: from chemicals and DNA via proteins to RNA.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685979}, issn = {1471-2970}, abstract = {The ability to target DNA specifically at any given position within the genome allows many intriguing possibilities and has inspired scientists for decades. Early gene-targeting efforts exploited chemicals or DNA oligonucleotides to interfere with the DNA at a given location in order to inactivate a gene or to correct mutations. We here describe an example towards correcting a genetic mutation underlying Pompe's disease using a nucleotide-fused nuclease (TFO-MunI). In addition to the promise of gene correction, scientists soon realized that genes could be inactivated or even re-activated without inducing potentially harmful DNA damage by targeting transcriptional modulators to a particular gene. However, it proved difficult to fuse protein effector domains to the first generation of programmable DNA-binding agents. The engineering of gene-targeting proteins (zinc finger proteins (ZFPs), transcription activator-like effectors (TALEs)) circumvented this problem. The disadvantage of protein-based gene targeting is that a fusion protein needs to be engineered for every locus. The recent introduction of CRISPR/Cas offers a flexible approach to target a (fusion) protein to the locus of interest using cheap designer RNA molecules. Many research groups now exploit this platform and the first human clinical trials have been initiated: CRISPR/Cas has kicked off a new era of gene targeting and is revolutionizing biomedical sciences.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685978, year = {2018}, author = {Hanly, DJ and Esteller, M and Berdasco, M}, title = {Interplay between long non-coding RNAs and epigenetic machinery: emerging targets in cancer?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685978}, issn = {1471-2970}, abstract = {Of the diverse array of putative molecular and biological functions assigned to long non-coding RNAs (lncRNAs), one attractive perspective in epigenetic research has been the hypothesis that lncRNAs directly interact with the proteins involved in the modulation of chromatin conformation. Indeed, epigenetic modifiers are among the most frequent protein partners of lncRNAs that have been identified to date, of which histone methyltransferases and protein members of the Polycomb Repressive Complex PRC2 have received considerable attention. This review is focused on how lncRNAs interface with epigenetic factors to shape the outcomes of crucial biological processes such as regulation of gene transcription, modulation of nuclear architecture, X inactivation in females and pre-mRNA splicing. Because of our increasing knowledge of their role in development and cellular differentiation, more research is beginning to be done into the deregulation of lncRNAs in human disorders. Focusing on cancer, we describe some key examples of disease-focused lncRNA studies. This knowledge has significantly contributed to our ever-improving understanding of how lncRNAs interact with epigenetic factors of human disease, and has also provided a plethora of much-needed novel prognostic biomarker candidates or potential therapeutic targets. Finally, current limitations and perspectives on lncRNA research are discussed here.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685977, year = {2018}, author = {Pacini, C and Koziol, MJ}, title = {Bioinformatics challenges and perspectives when studying the effect of epigenetic modifications on alternative splicing.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685977}, issn = {1471-2970}, support = {BB/M022994/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {It is widely known that epigenetic modifications are important in regulating transcription, but several have also been reported in alternative splicing. The regulation of pre-mRNA splicing is important to explain proteomic diversity and the misregulation of splicing has been implicated in many diseases. Here, we give a brief overview of the role of epigenetics in alternative splicing and disease. We then discuss the bioinformatics methods that can be used to model interactions between epigenetic marks and regulators of splicing. These models can be used to identify alternative splicing and epigenetic changes across different phenotypes.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685976, year = {2018}, author = {Halby, L and Marechal, N and Pechalrieu, D and Cura, V and Franchini, DM and Faux, C and Alby, F and Troffer-Charlier, N and Kudithipudi, S and Jeltsch, A and Aouadi, W and Decroly, E and Guillemot, JC and Page, P and Ferroud, C and Bonnefond, L and Guianvarc'h, D and Cavarelli, J and Arimondo, PB}, title = {Hijacking DNA methyltransferase transition state analogues to produce chemical scaffolds for PRMT inhibitors.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685976}, issn = {1471-2970}, abstract = {DNA, RNA and histone methylation is implicated in various human diseases such as cancer or viral infections, playing a major role in cell process regulation, especially in modulation of gene expression. Here we developed a convergent synthetic pathway starting from a protected bromomethylcytosine derivative to synthesize transition state analogues of the DNA methyltransferases. This approach led to seven 5-methylcytosine-adenosine compounds that were, surprisingly, inactive against hDNMT1, hDNMT3Acat, TRDMT1 and other RNA human and viral methyltransferases. Interestingly, compound 4 and its derivative 2 showed an inhibitory activity against PRMT4 in the micromolar range. Crystal structures showed that compound 4 binds to the PRMT4 active site, displacing strongly the S-adenosyl-l-methionine cofactor, occupying its binding site, and interacting with the arginine substrate site through the cytosine moiety that probes the space filled by a substrate peptide methylation intermediate. Furthermore, the binding of the compounds induces important structural switches. These findings open new routes for the conception of new potent PRMT4 inhibitors based on the 5-methylcytosine-adenosine scaffold.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685975, year = {2018}, author = {Bonnici, J and Tumber, A and Kawamura, A and Schofield, CJ}, title = {Inhibitors of both the N-methyl lysyl- and arginyl-demethylase activities of the JmjC oxygenases.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685975}, issn = {1471-2970}, abstract = {The Jumonji C (JmjC) family of 2-oxoglutarate (2OG)-dependent oxygenases have established roles in the regulation of transcription via the catalysis of demethylation of Nε-methylated lysine residues in histone tails, especially the N-terminal tail of histone H3. Most human JmjC Nɛ -methyl lysine demethylases (KDMs) are complex enzymes, with 'reader domains' in addition to their catalytic domains. Recent biochemical evidence has shown that some, but not all, JmjC KDMs also have Nω-methyl arginyl demethylase (RDM) activity. JmjC KDM activity has been linked to multiple cancers and some JmjC proteins are therapeutic targets. It is, therefore, important to test not only whether compounds in development inhibit the KDM activity of targeted JmjC demethylases, but also whether they inhibit other activities of these proteins. Here we report biochemical studies on the potential dual inhibition of JmjC KDM and RDM activities using a model JmjC demethylase, KDM4E (JMJD2E). The results reveal that all of the tested compounds inhibit both the KDM and RDM activities, raising questions about the in vivo effects of the inhibitors.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685974, year = {2018}, author = {Kudo, N and Ito, A and Arata, M and Nakata, A and Yoshida, M}, title = {Identification of a novel small molecule that inhibits deacetylase but not defatty-acylase reaction catalysed by SIRT2.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685974}, issn = {1471-2970}, abstract = {SIRT2 is a member of the human sirtuin family of proteins and possesses NAD+-dependent lysine deacetylase/deacylase activity. SIRT2 has been implicated in carcinogenesis in various cancers including leukaemia and is considered an attractive target for cancer therapy. Here, we identified NPD11033, a selective small-molecule SIRT2 inhibitor, by a high-throughput screen using the RIKEN NPDepo chemical library. NPD11033 was largely inactive against other sirtuins and zinc-dependent deacetylases. Crystallographic analysis revealed a unique mode of action, in which NPD11033 creates a hydrophobic cavity behind the substrate-binding pocket after a conformational change of the Zn-binding small domain of SIRT2. Furthermore, it forms a hydrogen bond to the active site histidine residue. In addition, NPD11033 inhibited cell growth of human pancreatic cancer PANC-1 cells with a concomitant increase in the acetylation of eukaryotic translation initiation factor 5A, a physiological substrate of SIRT2. Importantly, NPD11033 failed to inhibit defatty-acylase activity of SIRT2, despite its potent inhibitory effect on its deacetylase activity. Thus, NPD11033 will serve as a useful tool for both developing novel anti-cancer agents and elucidating the role of SIRT2 in various cellular biological processes.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685973, year = {2018}, author = {Ganesan, A}, title = {Epigenetic drug discovery: a success story for cofactor interference.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685973}, issn = {1471-2970}, abstract = {Within the past two decades, seven epigenetic drugs have received regulatory approval and numerous other candidates are currently in clinical trials. Among the epigenetic targets are the writer and eraser enzymes that are, respectively, responsible for the reversible introduction and removal of structural modifications in the nucleosome. This review discusses the progress achieved in the design and development of inhibitors against the key writer and eraser pairs: DNA methyltransferases and Tet demethylases; lysine/arginine methyltransferases and lysine demethylases; and histone acetyltransferases and histone deacetylases. A common theme for the successful inhibition of these enzymes in a potent and selective manner is the targeting of the cofactors present in the active site, namely zinc and iron cations, S-adenosylmethione, nicotinamide adenine dinucleotide, flavin adenine dinucleotide and acetyl Coenzyme A.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685972, year = {2018}, author = {Ronan, JL and Kadi, N and McMahon, SA and Naismith, JH and Alkhalaf, LM and Challis, GL}, title = {Desferrioxamine biosynthesis: diverse hydroxamate assembly by substrate-tolerant acyl transferase DesC.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685972}, issn = {1471-2970}, abstract = {Hydroxamate groups play key roles in the biological function of diverse natural products. Important examples include trichostatin A, which inhibits histone deacetylases via coordination of the active site zinc(II) ion with a hydroxamate group, and the desferrioxamines, which use three hydroxamate groups to chelate ferric iron. Desferrioxamine biosynthesis in Streptomyces species involves the DesD-catalysed condensation of various N-acylated derivatives of N-hydroxycadaverine with two molecules of N-succinyl-N-hydroxycadaverine to form a range of linear and macrocyclic tris-hydroxamates. However, the mechanism for assembly of the various N-acyl-N-hydroxycadaverine substrates of DesD from N-hydroxycadaverine has until now been unclear. Here we show that the desC gene of Streptomyces coelicolor encodes the acyl transferase responsible for this process. DesC catalyses the N-acylation of N-hydroxycadaverine with acetyl, succinyl and myristoyl-CoA, accounting for the diverse array of desferrioxamines produced by S. coelicolor The X-ray crystal structure of DesE, the ferrioxamine lipoprotein receptor, in complex with ferrioxamine B (which is derived from two units of N-succinyl-N-hydroxycadaverine and one of N-acetyl-N-hydroxycadaverine) was also determined. This showed that the acetyl group of ferrioxamine B is solvent exposed, suggesting that the corresponding acyl group in longer chain congeners can protrude from the binding pocket, providing insights into their likely function. This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685971, year = {2018}, author = {Ganesan, A}, title = {Epigenetics: the first 25 centuries.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685971}, issn = {1471-2970}, abstract = {Epigenetics is a natural progression of genetics as it aims to understand how genes and other heritable elements are regulated in eukaryotic organisms. The history of epigenetics is briefly reviewed, together with the key issues in the field today. This themed issue brings together a diverse collection of interdisciplinary reviews and research articles that showcase the tremendous recent advances in epigenetic chemical biology and translational research into epigenetic drug discovery.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685970, year = {2018}, author = {Sallis, H and Davey Smith, G and Munafò, MR}, title = {Correction to 'Genetics of biologically based psychological differences'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, doi = {10.1098/rstb.2018.0173}, pmid = {29685970}, issn = {1471-2970}, } @article {pmid29685969, year = {2018}, author = {Lecointre, B and Narozny, R and Borrello, MT and Senger, J and Chakrabarti, A and Jung, M and Marek, M and Romier, C and Melesina, J and Sippl, W and Bischoff, L and Ganesan, A}, title = {Isoform-selective HDAC1/6/8 inhibitors with an imidazo-ketopiperazine cap containing stereochemical diversity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685969}, issn = {1471-2970}, abstract = {A series of hydroxamic acids linked by different lengths to a chiral imidazo-ketopiperazine scaffold were synthesized. The compounds with linker lengths of 6 and 7 carbon atoms were the most potent in histone deacetylase (HDAC) inhibition, and were specific submicromolar inhibitors of the HDAC1, HDAC6 and HDAC8 isoforms. A docking model for the binding mode predicts binding of the hydroxamic acid to the active site zinc cation and additional interactions between the imidazo-ketopiperazine and the enzyme rim. The compounds were micromolar inhibitors of the MV4-11, THP-1 and U937 cancer cell lines. Increased levels of histone H3 and tubulin acetylation support a cellular mechanism of action through HDAC inhibition.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685968, year = {2018}, author = {Gerhauser, C}, title = {Impact of dietary gut microbial metabolites on the epigenome.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685968}, issn = {1471-2970}, abstract = {Within the past decade, epigenetic mechanisms and their modulation by natural products have gained increasing interest. Dietary bioactive compounds from various sources, including green tea, soya, fruit and berries, cruciferous vegetables, whole grain foods, fish and others, have been shown to target enzymes involved in epigenetic gene regulation, including DNA methyltransferases, histone acetyltransferases, deacetylases and demethylases in vitro and in cell culture. Also, many dietary agents were shown to alter miRNA expression. In vivo studies in animal models and humans are still limited. Recent research has indicated that the gut microbiota and gut microbial metabolites might be important mediators of diet-epigenome interactions. Inter-individual differences in the gut microbiome might affect release, metabolism and bioavailability of dietary agents and explain variability in response to intervention in human studies. Only a few microbial metabolites, including folate, phenolic acids, S-(-)equol, urolithins, isothiocyanates, and short- and long-chain fatty acids have been tested with respect to their potential to influence epigenetic mechanisms. Considering that a complex mixture of intermediary and microbial metabolites is present in human circulation, a more systematic interdisciplinary investigation of nutri-epigenetic activities and their impact on human health is called for.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685967, year = {2018}, author = {Vilela-Salgueiro, B and Barros-Silva, D and Lobo, J and Costa, AL and Guimarães, R and Cantante, M and Lopes, P and Braga, I and Oliveira, J and Henrique, R and Jerónimo, C}, title = {Germ cell tumour subtypes display differential expression of microRNA371a-3p.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685967}, issn = {1471-2970}, abstract = {Testicular germ cell tumours (TGCTs) are a heterogeneous group of neoplasms, mostly affecting young men. Curability rates are high and adequate treatment relies on careful and accurate pathological and clinical assessment. Indeed, TGCTs' histopathological subtyping is critical for adequate therapeutic decision. Considering the limitation of currently available serum biomarkers, novel candidates have been proposed, most notably miR-371a-3p, which outperformed classical serum markers, but no detailed information concerning TGCT subtype was available. Thus, we carried out evaluation of miR-371a-3p expression levels among TGCT subtypes using a consecutive cohort of tissue samples. MiR-371a-3p discriminated TGCTs from control tissues with high sensitivity and specificity (AUC = 0.99). Furthermore, seminomas displayed higher miR-371a-3p expression levels compared to non-seminomatous TGCTs, which also showed significant differences among them. Nonetheless, prepubertal TGCTs depicted lower miR-371a-3p expression levels than postpubertal TGCTs. Globally, miR-371a-3p expression levels decreased in parallel with progressive cell differentiation. We concluded that miR-371a-3p is TGCTs-specific and it might be clinically useful for early detection and disease monitoring.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685966, year = {2018}, author = {Alexeeva, M and Guragain, P and Tesfahun, AN and Tomkuvienė, M and Arshad, A and Gerasimaitė, R and Rukšėnaitė, A and Urbanavičiūtė, G and Bjørås, M and Laerdahl, JK and Klungland, A and Klimašauskas, S and Bjelland, S}, title = {Excision of the doubly methylated base N4,5-dimethylcytosine from DNA by Escherichia coli Nei and Fpg proteins.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685966}, issn = {1471-2970}, abstract = {Cytosine (C) in DNA is often modified to 5-methylcytosine (m5C) to execute important cellular functions. Despite the significance of m5C for epigenetic regulation in mammals, damage to m5C has received little attention. For instance, almost no studies exist on erroneous methylation of m5C by alkylating agents to doubly or triply methylated bases. Owing to chemical evidence, and because many prokaryotes express methyltransferases able to convert m5C into N4,5-dimethylcytosine (m N 4,5C) in DNA, m N 4,5C is probably present in vivo We screened a series of glycosylases from prokaryotic to human and found significant DNA incision activity of the Escherichia coli Nei and Fpg proteins at m N 4,5C residues in vitro The activity of Nei was highest opposite cognate guanine followed by adenine, thymine (T) and C. Fpg-complemented Nei by exhibiting the highest activity opposite C followed by lower activity opposite T. To our knowledge, this is the first description of a repair enzyme activity at a further methylated m5C in DNA, as well as the first alkylated base allocated as a Nei or Fpg substrate. Based on our observed high sensitivity to nuclease S1 digestion, we suggest that m N 4,5C occurs as a disturbing lesion in DNA and that Nei may serve as a major DNA glycosylase in E. coli to initiate its repair.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685965, year = {2018}, author = {Mellini, P and Marrocco, B and Borovika, D and Polletta, L and Carnevale, I and Saladini, S and Stazi, G and Zwergel, C and Trapencieris, P and Ferretti, E and Tafani, M and Valente, S and Mai, A}, title = {Pyrazole-based inhibitors of enhancer of zeste homologue 2 induce apoptosis and autophagy in cancer cells.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685965}, issn = {1471-2970}, abstract = {Novel pyrazole-based EZH2 inhibitors have been prepared through a molecular pruning approach from known inhibitors bearing a bicyclic moiety as a central scaffold. The hit compound 1o (N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-5-methyl-1-phenyl-1H-pyrazole-4-carboxamide) showed low micromolar EZH2/PRC2 inhibition and high selectivity towards a panel of other methyltransferases. Moreover, 1o displayed cell growth arrest in breast MDA-MB231, leukaemia K562, and neuroblastoma SK-N-BE cancer cells joined to reduction of H3K27me3 levels and induction of apoptosis and autophagy.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685964, year = {2018}, author = {Riffo-Campos, AL and Fuentes-Trillo, A and Tang, WY and Soriano, Z and De Marco, G and Rentero-Garrido, P and Adam-Felici, V and Lendinez-Tortajada, V and Francesconi, K and Goessler, W and Ladd-Acosta, C and Leon-Latre, M and Casasnovas, JA and Chaves, FJ and Navas-Acien, A and Guallar, E and Tellez-Plaza, M}, title = {In silico epigenetics of metal exposure and subclinical atherosclerosis in middle aged men: pilot results from the Aragon Workers Health Study.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685964}, issn = {1471-2970}, abstract = {We explored the association of metal levels with subclinical atherosclerosis and epigenetic changes in relevant biological pathways. Whole blood DNA Infinium Methylation 450 K data were obtained from 23 of 73 middle age men without clinically evident cardiovascular disease (CVD) who participated in the Aragon Workers Health Study in 2009 (baseline visit) and had available baseline urinary metals and subclinical atherosclerosis measures obtained in 2010-2013 (follow-up visit). The median metal levels were 7.36 µg g-1, 0.33 µg g-1, 0.11 µg g-1 and 0.07 µg g-1, for arsenic (sum of inorganic and methylated species), cadmium, antimony and tungsten, respectively. Urine cadmium and tungsten were associated with femoral and carotid intima-media thickness, respectively (Pearson's r = 0.27; p = 0.03 in both cases). Among nearest genes to identified differentially methylated regions (DMRs), 46% of metal-DMR genes overlapped with atherosclerosis-DMR genes (p < 0.001). Pathway enrichment analysis of atherosclerosis-DMR genes showed a role in inflammatory, metabolic and transport pathways. In in silico protein-to-protein interaction networks among proteins encoded by 162 and 108 genes attributed to atherosclerosis- and metal-DMRs, respectively, with proteins known to have a role in atherosclerosis pathways, we observed hub proteins in the network associated with both atherosclerosis and metal-DMRs (e.g. SMAD3 and NOP56), and also hub proteins associated with metal-DMRs only but with relevant connections with atherosclerosis effectors (e.g. SSTR5, HDAC4, AP2A2, CXCL12 and SSTR4). Our integrative in silico analysis demonstrates the feasibility of identifying epigenomic regions linked to environmental exposures and potentially involved in relevant pathways for human diseases. While our results support the hypothesis that metal exposures can influence health due to epigenetic changes, larger studies are needed to confirm our pilot results.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685963, year = {2018}, author = {Swyter, S and Schiedel, M and Monaldi, D and Szunyogh, S and Lehotzky, A and Rumpf, T and Ovádi, J and Sippl, W and Jung, M}, title = {New chemical tools for probing activity and inhibition of the NAD+-dependent lysine deacylase sirtuin 2.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685963}, issn = {1471-2970}, abstract = {Sirtuins are NAD+-dependent protein deacylases capable of cleaving off acetyl as well as other acyl groups from the ɛ-amino group of lysines in histones and other substrate proteins. They have been reported as promising drug targets, and thus modulators of their activity are needed as molecular tools to uncover their biological function and as potential therapeutics. Here, we present new assay formats that complement existing assays for sirtuin biochemistry and cellular target engagement. Firstly, we report the development of a homogeneous fluorescence-based activity assay using unlabelled acylated peptides. Upon deacylation, the free lysine residue reacts with fluorescamine to form a fluorophore. Secondly, using click chemistry with a TAMRA-azide on a propargylated sirtuin inhibitor, we prepared the first fluorescently labelled small-molecule inhibitor of Sirt2. This is used in a binding assay, which is based on fluorescence polarization. We used it successfully to map potential inhibitor-binding sites and also to show cellular Sirt2 engagement. By means of these new assays, we were able to identify and characterize novel Sirt2 inhibitors out of a focused library screen. The binding of the identified Sirt2 inhibitors was rationalized by molecular docking studies. These new chemical tools thus can enhance further sirtuin research.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685962, year = {2018}, author = {Copeland, RA}, title = {Protein methyltransferase inhibitors as precision cancer therapeutics: a decade of discovery.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1748}, pages = {}, pmid = {29685962}, issn = {1471-2970}, abstract = {The protein methyltransferases (PMTs) represent a large class of enzymes that catalyse the methylation of side chain nitrogen atoms of the amino acids lysine or arginine at specific locations along the primary sequence of target proteins. These enzymes play a key role in the spatio-temporal control of gene transcription by performing site-specific methylation of lysine or arginine residues within the histone proteins of chromatin, thus effecting chromatin conformational changes that activate or repress gene transcription. Over the past decade, it has become clear that the dysregulated activity of some PMTs plays an oncogenic role in a number of human cancers. Here we review research of the past decade that has identified specific PMTs as oncogenic drivers of cancers and progress toward the discovery and development of selective, small molecule inhibitors of these enzymes as precision cancer therapeutics.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.}, } @article {pmid29685754, year = {2018}, author = {Baab, KL and Copes, LE and Ward, DL and Wells, N and Grine, FE}, title = {Using modern human cortical bone distribution to test the systemic robusticity hypothesis.}, journal = {Journal of human evolution}, volume = {119}, number = {}, pages = {64-82}, doi = {10.1016/j.jhevol.2018.03.003}, pmid = {29685754}, issn = {1095-8606}, abstract = {The systemic robusticity hypothesis links the thickness of cortical bone in both the cranium and limb bones. This hypothesis posits that thick cortical bone is in part a systemic response to circulating hormones, such as growth hormone and thyroid hormone, possibly related to physical activity or cold climates. Although this hypothesis has gained popular traction, only rarely has robusticity of the cranium and postcranial skeleton been considered jointly. We acquired computed tomographic scans from associated crania, femora and humeri from single individuals representing 11 populations in Africa and North America (n = 228). Cortical thickness in the parietal, frontal and occipital bones and cortical bone area in limb bone diaphyses were analyzed using correlation, multiple regression and general linear models to test the hypothesis. Absolute thickness values from the crania were not correlated with cortical bone area of the femur or humerus, which is at odds with the systemic robusticity hypothesis. However, measures of cortical bone scaled by total vault thickness and limb cross-sectional area were positively correlated between the cranium and postcranium. When accounting for a range of potential confounding variables, including sex, age and body mass, variation in relative postcranial cortical bone area explained ∼20% of variation in the proportion of cortical cranial bone thickness. While these findings provide limited support for the systemic robusticity hypothesis, cranial cortical thickness did not track climate or physical activity across populations. Thus, some of the variation in cranial cortical bone thickness in modern humans is attributable to systemic effects, but the driving force behind this effect remains obscure. Moreover, neither absolute nor proportional measures of cranial cortical bone thickness are positively correlated with total cranial bone thickness, complicating the extrapolation of these findings to extinct species where only cranial vault thickness has been measured.}, } @article {pmid29685753, year = {2018}, author = {Peterson, A and Abella, EF and Grine, FE and Teaford, MF and Ungar, PS}, title = {Microwear textures of Australopithecus africanus and Paranthropus robustus molars in relation to paleoenvironment and diet.}, journal = {Journal of human evolution}, volume = {119}, number = {}, pages = {42-63}, doi = {10.1016/j.jhevol.2018.02.004}, pmid = {29685753}, issn = {1095-8606}, abstract = {The importance of diet in primate ecology has motivated the use of a variety of methods to reconstruct dietary habits of extinct hominin taxa. Dental microwear is one such approach that preserves evidence from consumed food items. This study is based on 44 specimens of Australopithecus africanus from Makapansgat and Sterkfontein, and 66 specimens of Paranthropus robustus from Swartkrans, Kromdraai and Drimolen. These samples enable examination of potential differences between the two assemblages of A. africanus, and among the various assemblages of P. robustus in relation to the paleoenvironmental reconstructions that have been proffered for each fossil site. Sixteen microwear texture variables were recorded for each specimen from digital elevation models generated using a white-light confocal profiler. Only two of these differ significantly between the Makapansgat and Sterkfontein samples of A. africanus. None of the microwear texture variables differs significantly among the samples of P. robustus. On the other hand, P. robustus has significantly higher values than A. africanus for 11 variables related to feature complexity, size, and depth; P. robustus exhibits rougher surfaces that comprise larger, deeper features. In contrast, A. africanus has smoother, simpler wear surfaces with smaller, shallower and more anisotropic features. As for possible habitat differences among the various sites, only a relatively small number of subtle differences are evident between the specimens of A. africanus from Makapansgat and Sterkfontein, and there are none among the specimens of P. robustus from various deposits. As such, it is reasonable to conclude that, while subtle differences in microwear textures may reflect differences in background habitats, the wear fabric differences between P. robustus and A. africanus are most reasonably interpreted as having been driven by dietary differences.}, } @article {pmid29685752, year = {2018}, author = {Power, RC and Salazar-García, DC and Rubini, M and Darlas, A and Harvati, K and Walker, M and Hublin, JJ and Henry, AG}, title = {Dental calculus indicates widespread plant use within the stable Neanderthal dietary niche.}, journal = {Journal of human evolution}, volume = {119}, number = {}, pages = {27-41}, doi = {10.1016/j.jhevol.2018.02.009}, pmid = {29685752}, issn = {1095-8606}, abstract = {The ecology of Neanderthals is a pressing question in the study of hominin evolution. Diet appears to have played a prominent role in their adaptation to Eurasia. Based on isotope and zooarchaeological studies, Neanderthal diet has been reconstructed as heavily meat-based and generally similar across different environments. This image persists, despite recent studies suggesting more plant use and more variation. However, we have only a fragmentary picture of their dietary ecology, and how it may have varied among habitats, because we lack broad and environmentally representative information about their use of plants and other foods. To address the problem, we examined the plant microremains in Neanderthal dental calculus from five archaeological sites representing a variety of environments from the northern Balkans, and the western, central and eastern Mediterranean. The recovered microremains revealed the consumption of a variety of non-animal foods, including starchy plants. Using a modeling approach, we explored the relationships among microremains and environment, while controlling for chronology. In the process, we compared the effectiveness of various diversity metrics and their shortcomings for studying microbotanical remains, which are often morphologically redundant for identification. We developed Minimum Botanical Units as a new way of estimating how many plant types or parts are present in a microbotanical sample. In contrast to some previous work, we found no evidence that plant use is confined to the southern-most areas of Neanderthal distribution. Although interpreting the ecogeographic variation is limited by the incomplete preservation of dietary microremains, it is clear that plant exploitation was a widespread and deeply rooted Neanderthal subsistence strategy, even if they were predominately game hunters. Given the limited dietary variation across Neanderthal range in time and space in both plant and animal food exploitation, we argue that vegetal consumption was a feature of a generally static dietary niche.}, } @article {pmid29685751, year = {2018}, author = {Williams-Hatala, EM and Hatala, KG and Gordon, M and Key, A and Kasper, M and Kivell, TL}, title = {The manual pressures of stone tool behaviors and their implications for the evolution of the human hand.}, journal = {Journal of human evolution}, volume = {119}, number = {}, pages = {14-26}, doi = {10.1016/j.jhevol.2018.02.008}, pmid = {29685751}, issn = {1095-8606}, abstract = {It is widely agreed that biomechanical stresses imposed by stone tool behaviors influenced the evolution of the human hand. Though archaeological evidence suggests that early hominins participated in a variety of tool behaviors, it is unlikely that all behaviors equally influenced modern human hand anatomy. It is more probable that a behavior's likelihood of exerting a selective pressure was a weighted function of the magnitude of stresses associated with that behavior, the benefits received from it, and the amount of time spent performing it. Based on this premise, we focused on the first part of that equation and evaluated magnitudes of stresses associated with stone tool behaviors thought to have been commonly practiced by early hominins, to determine which placed the greatest loads on the digits. Manual pressure data were gathered from 39 human subjects using a Novel Pliance® manual pressure system while they participated in multiple Plio-Pleistocene tool behaviors: nut-cracking, marrow acquisition with a hammerstone, flake production with a hammerstone, and handaxe and flake use. Manual pressure distributions varied significantly according to behavior, though there was a tendency for regions of the hand subject to the lowest pressures (e.g., proximal phalanges) to be affected less by behavior type. Hammerstone use during marrow acquisition and flake production consistently placed the greatest loads on the digits collectively, on each digit and on each phalanx. Our results suggest that, based solely on the magnitudes of stresses, hammerstone use during marrow acquisition and flake production are the most likely of the assessed behaviors to have influenced the anatomical and functional evolution of the human hand.}, } @article {pmid29685750, year = {2018}, author = {Ito, T and Lee, YJ and Nishimura, TD and Tanaka, M and Woo, JY and Takai, M}, title = {Phylogenetic relationship of a fossil macaque (Macaca cf. robusta) from the Korean Peninsula to extant species of macaques based on zygomaxillary morphology.}, journal = {Journal of human evolution}, volume = {119}, number = {}, pages = {1-13}, doi = {10.1016/j.jhevol.2018.02.002}, pmid = {29685750}, issn = {1095-8606}, abstract = {Little is known about the biogeographical and evolutionary histories of macaques (Macaca spp.) in East Asia because the phylogenetic positions of fossil species remain unclear. Here we examined the zygomaxillary remains of a fossil macaque (M. cf. robusta) from the Durubong Cave Complex, South Korea, that dates back to the late Middle to Late Pleistocene, to infer its phylogenetic relationship to extant species. We took 195 fixed- and semi-landmarks from the zygomaxillary regions of the fossil specimen and from 147 specimens belonging to 14 extant species. We then conducted a generalized Procrustes analysis followed by a multivariate statistical analysis to evaluate the phenetic affinities of the fossil to the extant species and reconstructed the most parsimonious phylogenetic tree using a phylogenetic morphometric approach. We found that the fossil was most similar to Macaca fuscata (Japanese macaque) in the zygomaxillary morphospace although it was at the limit of the range of variation for this species. The second closest in the morphospace was the continental Macaca mulatta (rhesus macaque). Parsimonious reconstruction confirmed that the fossil was most closely related to M. fuscata, even after controlling for the effects of allometry. These findings suggest that in the late Middle to Late Pleistocene, close relatives of M. fuscata that looked like the extant species were distributed on the Korean Peninsula, where no species of macaques are found today. Thus, some morphological characteristics of M. fuscata may have developed before its ancestor dispersed into the Japanese archipelago.}, } @article {pmid29685749, year = {2018}, author = {Wessling, EG and Kühl, HS and Mundry, R and Deschner, T and Pruetz, JD}, title = {The costs of living at the edge: Seasonal stress in wild savanna-dwelling chimpanzees.}, journal = {Journal of human evolution}, volume = {121}, number = {}, pages = {1-11}, doi = {10.1016/j.jhevol.2018.03.001}, pmid = {29685749}, issn = {1095-8606}, abstract = {Adaptations associated with shifting from a predominately forested habitat to a more open environment are considered a crucial step in hominin evolution. Understanding how chimpanzees, one of our closest-living relatives, are exposed to the selection pressures associated with living in a relatively sparse, hot, and dry environment can inform us about the relative importance of potential environmental stressors involved in adaptations to drier environments. We investigated the extent to which chimpanzees living in an extreme savanna habitat experience seasonal variability in either energy balance or thermoregulation (dehydration and heat exposure), as well as whether these potential environmental constraints are taxing to chimpanzee individuals. Specifically, we tested the hypothesis that savanna environments impose seasonally-relevant costs to chimpanzees. To this end, we collected 368 urine samples from one community of chimpanzees at Fongoli, Senegal, and measured c-peptide, creatinine, and cortisol as measures of physiological responses to environmental food, water, and heat constraints, respectively. We then evaluated the influence of climatic and phenological factors on these indicators. Results illustrated significant seasonal variation in all biomarkers, which corresponded to relevant ecological correlates. Furthermore, creatinine but not c-peptide correlated with cortisol levels, suggesting that chimpanzees in this environment endure periods of heat and dehydration stress, but are able to avoid stressful levels of negative energy balance. Using savanna chimpanzees as a referential model, our research lends support to the notion that thermoregulatory challenges were a significant factor in hominin evolution, and suggests these challenges may have overshadowed the challenges of maintaining adequate energetic balance during the expansion of the hominin range from wetter to drier environments.}, } @article {pmid29685748, year = {2018}, author = {Stanistreet, IG and McHenry, LJ and Stollhofen, H and de la Torre, I}, title = {Bed II Sequence Stratigraphic context of EF-HR and HWK EE archaeological sites, and the Oldowan/Acheulean succession at Olduvai Gorge, Tanzania.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {19-31}, doi = {10.1016/j.jhevol.2018.01.005}, pmid = {29685748}, issn = {1095-8606}, abstract = {Archaeological excavations at EF-HR and HWK EE allow reassessment of Bed II stratigraphy within the Junction Area and eastern Olduvai Gorge. Application of Sequence Stratigraphic methods provides a time-stratigraphic framework enabling correlation of sedimentary units across facies boundaries, applicable even in those areas where conventional timelines, such as tephrostratigraphic markers, are absent, eroded, or reworked. Sequence Stratigraphically, Bed II subdivides into five major Sequences 1 to 5, all floored by major disconformities that incise deeply into the underlying succession, proving that simple "layer cake" stratigraphy is inappropriate. Previous establishment of the Lemuta Member has invalidated the use of Tuff IIA as the boundary between Lower and Middle Bed II, now redefined at the disconformity between Sequences 2 and 3, a lithostratigraphic contact underlying the succession containing the Lower, Middle, and Upper Augitic Sandstones. HWK EE site records Oldowan technology in the Lower Augitic Sandstone at the base of Sequence 3, within Middle Bed II. We suggest placement of recently reported Acheulean levels at FLK W within the Middle Augitic Sandstone, thus emphasizing that handaxes are yet to be found in earlier stratigraphic units of the Olduvai sequence. This would place a boundary between the Oldowan and Acheulean technologies at Olduvai in the Tuff IIB zone or earliest Middle Augitic Sandstone. A major disconformity between Sequences 3 and 4 at and near EF-HR cuts through the level of Tuff IIC, placing the main Acheulean EF-HR assemblage at the base of Sequence 4, within Upper rather than Middle Bed II. Sequence stratigraphic methods also yield a more highly resolved Bed II stratigraphic framework. Backwall and sidewall surveying of archaeological trenches at EF-HR and HWK EE permits definition of "Lake-parasequences" nested within the major Sequences that record downcutting of disconformities associated with lake regression, then sedimentation associated with lake transgression, capped finally by another erosional disconformity or hiatal paraconformity caused by the next lake withdrawal. On a relative time-scale rather than a vertical metre scale, the resulting Wheeler diagram framework provides a basis for recognizing time-equivalent depositional episodes and the position of time gaps at various scales. Relative timing of archaeological assemblage levels can then be differentiated at a millennial scale within this framework.}, } @article {pmid29685580, year = {2018}, author = {Silk, MJ and Finn, KR and Porter, MA and Pinter-Wollman, N}, title = {Can Multilayer Networks Advance Animal Behavior Research?.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {376-378}, pmid = {29685580}, issn = {1872-8383}, support = {R01 GM115509/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Behavior, Animal ; *Biological Evolution ; *Models, Biological ; *Social Behavior ; }, abstract = {Interactions among individual animals - and between these individuals and their environment - yield complex, multifaceted systems. The development of multilayer network analysis offers a promising new approach for studying animal social behavior and its relation to eco-evolutionary dynamics.}, } @article {pmid29685579, year = {2018}, author = {Sukumaran, J and Knowles, LL}, title = {Trait-Dependent Biogeography: (Re)Integrating Biology into Probabilistic Historical Biogeographical Models.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {390-398}, doi = {10.1016/j.tree.2018.03.010}, pmid = {29685579}, issn = {1872-8383}, mesh = {*Animal Distribution ; Computational Biology ; *Life History Traits ; Models, Biological ; Models, Statistical ; *Phenotype ; *Phylogeny ; *Phylogeography ; *Plant Dispersal ; }, abstract = {The development of process-based probabilistic models for historical biogeography has transformed the field by grounding it in modern statistical hypothesis testing. However, most of these models abstract away biological differences, reducing species to interchangeable lineages. We present here the case for reintegration of biology into probabilistic historical biogeographical models, allowing a broader range of questions about biogeographical processes beyond ancestral range estimation or simple correlation between a trait and a distribution pattern, as well as allowing us to assess how inferences about ancestral ranges themselves might be impacted by differential biological traits. We show how new approaches to inference might cope with the computational challenges resulting from the increased complexity of these trait-based historical biogeographical models.}, } @article {pmid29685177, year = {2018}, author = {Esteves, C and Neves, C and Sá, JJ and Carvalho, D}, title = {Severe hypoglycaemia in diabetic patients in Pre-hospital and Emergency Department care: a cross-sectional survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {249}, pmid = {29685177}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Diabetes Mellitus, Type 2/complications/*therapy ; Emergency Medical Services/economics/*statistics & numerical data ; Emergency Service, Hospital/economics/*statistics & numerical data ; Female ; Humans ; Hypoglycemia/etiology/*therapy ; Male ; Middle Aged ; Young Adult ; }, abstract = {OBJECTIVE: We aimed to characterize hypoglycaemia episodes and patients examined by a Pre-hospital Medical Emergency Unit (PH) and in the Emergency Department (ED) of our hospital.

RESULTS: We identified 86 episodes of severe hypoglycaemia (PH: n 37; ED: n 49; both: n 12). Hypoglycaemia accounted for 4.7% of all emergency calls attended by the PH (n 793) and 0.11% of all ED episodes (n 54,366). Among episodes examined by the PH, 64.5% of involved patients had type 2 diabetes and 54.1% were not referred to the ED. Transportation of the patient to the ED was more likely in type 2 diabetes (p = 0.014). Among episodes evaluated in the ED 66.1% of the patients were more than 65 years old and 81.4% had type 2 diabetes. 66% of the patients were insulin treated. One-third of examined patients were admitted to the ward, the majority having type 2 diabetes.}, } @article {pmid29685174, year = {2018}, author = {Fan, X and Peters, BA and Jacobs, EJ and Gapstur, SM and Purdue, MP and Freedman, ND and Alekseyenko, AV and Wu, J and Yang, L and Pei, Z and Hayes, RB and Ahn, J}, title = {Drinking alcohol is associated with variation in the human oral microbiome in a large study of American adults.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {59}, pmid = {29685174}, issn = {2049-2618}, support = {R01 CA159036/CA/NCI NIH HHS/United States ; U01CA182370/CA/NCI NIH HHS/United States ; R21CA183887/CA/NCI NIH HHS/United States ; Pancreas Cancer Action Network Career Development Award//American Association for Cancer Research/International ; P30CA016087/CA/NCI NIH HHS/United States ; R03CA159414/CA/NCI NIH HHS/United States ; R01CA159036/CA/NCI NIH HHS/United States ; R01CA164964/CA/NCI NIH HHS/United States ; R01 CA164964/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; *Alcohol Drinking ; Female ; Humans ; Male ; Metagenome ; Metagenomics ; *Microbiota ; Middle Aged ; Mouth/*microbiology ; Public Health Surveillance ; RNA, Ribosomal, 16S/genetics ; United States ; }, abstract = {BACKGROUND: Dysbiosis of the oral microbiome can lead to local oral disease and potentially to cancers of the head, neck, and digestive tract. However, little is known regarding exogenous factors contributing to such microbial imbalance.

RESULTS: We examined the impact of alcohol consumption on the oral microbiome in a cross-sectional study of 1044 US adults. Bacterial 16S rRNA genes from oral wash samples were amplified, sequenced, and assigned to bacterial taxa. We tested the association of alcohol drinking level (non-drinker, moderate drinker, or heavy drinker) and type (liquor, beer, or wine) with overall microbial composition and individual taxon abundance. The diversity of oral microbiota and overall bacterial profiles differed between heavy drinkers and non-drinkers (α-diversity richness p = 0.0059 and β-diversity unweighted UniFrac p = 0.0036), and abundance of commensal order Lactobacillales tends to be decreased with higher alcohol consumption (fold changes = 0.89 and 0.94 for heavy and moderate drinkers, p trend = 0.005 [q = 0.064]). Additionally, certain genera were enriched in subjects with higher alcohol consumption, including Actinomyces, Leptotrichia, Cardiobacterium, and Neisseria; some of these genera contain oral pathogens, while Neisseria can synthesize the human carcinogen acetaldehyde from ethanol. Wine drinkers may differ from non-drinkers in microbial diversity and profiles (α-diversity richness p = 0.048 and β-diversity unweighted UniFrac p = 0.059) after controlling for drinking amount, while liquor and beer drinkers did not. All significant differences between drinkers and non-drinkers remained after exclusion of current smokers.

CONCLUSIONS: Our results, from a large human study of alcohol consumption and the oral microbiome, indicate that alcohol consumption, and heavy drinking in particular, may influence the oral microbiome composition. These findings may have implications for better understanding the potential role that oral bacteria play in alcohol-related diseases.}, } @article {pmid29685170, year = {2018}, author = {Legese, H and Kahsay, AG and Kahsay, A and Araya, T and Adhanom, G and Muthupandian, S and Gebreyesus, A}, title = {Nasal carriage, risk factors and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus among healthcare workers in Adigrat and Wukro hospitals, Tigray, Northern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {250}, pmid = {29685170}, issn = {1756-0500}, mesh = {Adult ; Anti-Bacterial Agents/*pharmacology ; Ethiopia/epidemiology ; Female ; Hand/*microbiology ; Hospitals/*statistics & numerical data ; Humans ; Male ; Methicillin-Resistant Staphylococcus aureus/drug effects/isolation & purification ; Microbial Sensitivity Tests ; Middle Aged ; Nasal Cavity/*microbiology ; Nursing Staff, Hospital/statistics & numerical data ; Personnel, Hospital/*statistics & numerical data ; Staphylococcal Infections/*epidemiology/microbiology ; *Staphylococcus aureus/drug effects/isolation & purification ; Surgery Department, Hospital/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to determine nasal carriage, risk factors and antimicrobial susceptibility pattern of methicillin resistant Staphylococcus aureus among health care-workers of Adigrat and Wukro hospitals Northern Ethiopia.

RESULTS: The overall prevalence of S. aureus and methicillin resistance S. aureus (MRSA) in the present study were 12% (29/242) and 5.8% (14/242) respectively. The rate of MRSA among S. aureus was 48.3%(14/29). In this study, MRSA carriage was particularly higher among nurse professionals (7.8%) and surgical ward (17.1%). None of the MRSA isolates were sensitive to penicillin and ampicillin. However, low resistance was found for chloramphenicol and clindamycin. Being diabetic and use of hands rub was statistically significant with MRSA colonization.}, } @article {pmid29685108, year = {2018}, author = {Pyne, RM and Honig, JA and Vaiciunas, J and Wyenandt, CA and Simon, JE}, title = {Population structure, genetic diversity and downy mildew resistance among Ocimum species germplasm.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {69}, pmid = {29685108}, issn = {1471-2229}, support = {2011-51181-30646//USDA-Special Crops Research Initiative/International ; US-4947-16R//United States - Israel Binational Agricultural Research and Development Fund/International ; 2016-68004-24931//USDA - National Institute of Food and Agriculture/International ; }, mesh = {Disease Resistance/*genetics/immunology ; Genes, Plant/genetics ; Genetic Variation/genetics/immunology ; Ocimum/*genetics/immunology ; Ocimum basilicum/genetics/immunology ; *Peronospora ; Phylogeny ; Phylogeography ; Plant Diseases/*immunology/microbiology ; Ploidies ; }, abstract = {BACKGROUND: The basil (Ocimum spp.) genus maintains a rich diversity of phenotypes and aromatic volatiles through natural and artificial outcrossing. Characterization of population structure and genetic diversity among a representative sample of this genus is severely lacking. Absence of such information has slowed breeding efforts and the development of sweet basil (Ocimum basilicum L.) with resistance to the worldwide downy mildew epidemic, caused by the obligate oomycete Peronospora belbahrii. In an effort to improve classification of relationships 20 EST-SSR markers with species-level transferability were developed and used to resolve relationships among a diverse panel of 180 Ocimum spp. accessions with varying response to downy mildew.

RESULTS: Results obtained from nested Bayesian model-based clustering, analysis of molecular variance and unweighted pair group method using arithmetic average (UPGMA) analyses were synergized to provide an updated phylogeny of the Ocimum genus. Three (major) and seven (sub) population (cluster) models were identified and well-supported (P < 0.001) by PhiPT (ΦPT) values of 0.433 and 0.344, respectively. Allelic frequency among clusters supported previously developed hypotheses of allopolyploid genome structure. Evidence of cryptic population structure was demonstrated for the k1 O. basilicum cluster suggesting prevalence of gene flow. UPGMA analysis provided best resolution for the 36-accession, DM resistant k3 cluster with consistently strong bootstrap support. Although the k3 cluster is a rich source of DM resistance introgression of resistance into the commercially important k1 accessions is impeded by reproductive barriers as demonstrated by multiple sterile F1 hybrids. The k2 cluster located between k1 and k3, represents a source of transferrable tolerance evidenced by fertile backcross progeny. The 90-accession k1 cluster was largely susceptible to downy mildew with accession 'MRI' representing the only source of DM resistance.

CONCLUSIONS: High levels of genetic diversity support the observed phenotypic diversity among Ocimum spp. accessions. EST-SSRs provided a robust evaluation of molecular diversity and can be used for additional studies to increase resolution of genetic relationships in the Ocimum genus. Elucidation of population structure and genetic relationships among Ocimum spp. germplasm provide the foundation for improved DM resistance breeding strategies and more rapid response to future disease outbreaks.}, } @article {pmid29685105, year = {2018}, author = {Tang, X and Wang, Q and Yuan, H and Huang, X}, title = {Chilling-induced DNA Demethylation is associated with the cold tolerance of Hevea brasiliensis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {70}, pmid = {29685105}, issn = {1471-2229}, support = {31370608//the National Natural Science Foundation of China/ ; 31560197//the National Natural Science Foundation of China/ ; }, mesh = {Cold Temperature ; Cold-Shock Response ; CpG Islands/genetics ; *DNA Demethylation ; DNA Methylation ; Gene Expression Regulation, Plant ; Genes, Plant/genetics/physiology ; Geography ; Hevea/genetics/*physiology ; Promoter Regions, Genetic/genetics ; Seasons ; Sequence Analysis, DNA ; Transcriptome ; }, abstract = {BACKGROUND: Low temperature influences the development and latex production of rubber trees (Hevea brasiliensis) when extension to suboptimal high-latitude areas. The successful extension of Hevea brasiliensis cultivation to high-latitude areas has long believed to benefit from the breeding of cold-tolerant cultivars. A puzzling incongruity is the variation in cold tolerance among the cultivated clones despite their similar genetic make-up.

RESULTS: To investigate this, we first transferred cultivar Reyan 7-33-97 to short-term cold treatment, and showed that cold-related genes (such as HbICE1 and HbCBF2), cold-responsive (COR) genes, and DNA-methylation related genes (such as HbMET1) were induced by cold treatment. Furthermore, long-term cold treatment not only elevated the transcriptional activities of the HbICE1, HbCBF2, and HbMET, but also induced DNA demethylation of their promoters. Cold treatment increased the transcriptional activities of demethylation-related genes such as the HbDME, HbROS, and HbDML genes, but did not alter the promoter methylation status. Furthermore, the HbICE1 and HbMET promoters showed hypomethylation status in samples collected at the end of winter from 12 different cultivars grown in four geographical locations, but switched to hypermethylation status at the end of summer. Expression of COR was correlated with the low temperature. Given that little genetic diversity exists in the HbICE1 and HbMET promoters among different cultivars, the DNA demethylation induced by cold was highly correlated with low temperature, but not with the genetic backgrounds of cultivars.

CONCLUSION: Cold-induced epigenetic modification might play an important role in cold tolerance of H. brasiliensis.}, } @article {pmid29685104, year = {2018}, author = {Jin, X and Feng, B and Xu, Z and Fan, X and Liu, J and Liu, Q and Zhu, P and Wang, T}, title = {TaAAP6-3B, a regulator of grain protein content selected during wheat improvement.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {71}, pmid = {29685104}, issn = {1471-2229}, support = {2016ZX08009003-004//National Key Project of Transgenic Biologic Varieties Breeding/ ; 2014CB138104-2//National Basic Research Program of China/ ; 2016YFD0102000//National Key Research and Development Program of China/ ; }, mesh = {Alleles ; Edible Grain/genetics/growth & development ; Genes, Plant/*genetics/physiology ; Genetic Loci/genetics ; Grain Proteins/*metabolism ; Phylogeny ; Plant Breeding ; Polymorphism, Single Nucleotide/genetics ; Triticum/*genetics/metabolism ; }, abstract = {BACKGROUND: The content of grain protein (GPC) in cereals is an important part of total protein in human food. Exploring and utilizing new GPC genes is one of the most effective approaches for wheat quality breeding.

RESULTS: Three homoeologues of TaAAP6(-3A, 3B, 3D)were cloned by homology cloning from OsAAP6.Temporal and spatial expression analysis showed that TaAAP6homoeologues were preferentially expressed in developing grains, and TaAAP6-3B may play a major role in regulating GPC in wheat. Association analysis indicated thatTaAAP6-3B-I is significantly correlated with higher GPC than that of TaAAP6-3B-II for 115 wheat lines in all five environments. TaAAP6-3B-I, the favored allele of TaAAP6-3B, was preferentially expressed in preliminary developing grain stage. Two functional markers were developed to discriminate 197F2populations and the result showed that TaAAP6-3B-I (high-protein content) was completely dominant. Two cis-regulatory elements appear to be associated with high GPC were found in the 5'UTR of TaAAP6-3B-I.The change of the TaAAP6-3B locus types indicated that the gene was subjected to selection pressures during long process of artificial selection.

CONCLUSIONS: TaAAP6-3B is a regulator of GPC and its favored allele TaAAP6-3B-I exhibits an obvious potential application in wheat high-GPC breeding.}, } @article {pmid29685103, year = {2018}, author = {Wang, X and Lin, L and Tang, Y and Xia, H and Zhang, X and Yue, M and Qiu, X and Xu, K and Wang, Z}, title = {Transcriptomic insights into citrus segment membrane's cell wall components relating to fruit sensory texture.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {280}, pmid = {29685103}, issn = {1471-2164}, mesh = {Cell Wall/*metabolism ; Citrus/*cytology/*metabolism ; Fruit/*metabolism ; *Gene Expression Profiling ; Lignin/metabolism ; Membranes/cytology ; Pectins/metabolism ; Polysaccharides/metabolism ; *Taste ; }, abstract = {BACKGROUND: During fresh fruit consumption, sensory texture is one factor that affects the organoleptic qualities. Chemical components of plant cell walls, including pectin, cellulose, hemicellulose and lignin, play central roles in determining the textural qualities. To explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture, we performed mRNA-seq analyses of the segment membranes of two citrus cultivars, Shiranui and Kiyomi, with different organoleptic textures.

RESULTS: Segment membranes were sampled at two developmental stages of citrus fruit, the beginning and end of the expansion period. More than 3000 differentially expressed genes were identified. The gene ontology analysis revealed that more categories were significantly enriched in 'Shiranui' than in 'Kiyomi' at both developmental stages. In total, 108 significantly enriched pathways were obtained, with most belonging to metabolism. A detailed transcriptomic analysis revealed potential critical genes involved in the metabolism of cell wall structures, for example, GAUT4 in pectin synthesis, CESA1, 3 and 6, and SUS4 in cellulose synthesis, CSLC5, XXT1 and XXT2 in hemicellulose synthesis, and CSE in lignin synthesis. Low levels, or no expression, of genes involved in cellulose and hemicellulose, such as CESA4, CESA7, CESA8, IRX9 and IRX14, confirmed that secondary cell walls were negligible or absent in citrus segment membranes. A chemical component analysis of the segment membranes from mature fruit revealed that the pectin, cellulose and lignin contents, and the segment membrane's weight (% of segment) were greater in 'Kiyomi'.

CONCLUSION: Organoleptic quality of citrus is easily overlooked. It is mainly determined by sensory texture perceived in citrus segment membrane properties. We performed mRNA-seq analyses of citrus segment membranes to explore the genes and regulatory pathways involved in fresh citrus' perceived sensory texture. Transcriptomic data showed high repeatability between two independent biological replicates. The expression levels of genes involved in cell wall structure metabolism, including pectin, cellulose, hemicellulose and lignin, were investigated. Meanwhile, chemical component contents of the segment membranes from mature fruit were analyzed. This study provided detailed transcriptional regulatory profiles of different organoleptic citrus qualities and integrated insights into the mechanisms affecting citrus' sensory texture.}, } @article {pmid29685102, year = {2018}, author = {Mishima, K and Hirao, T and Tsubomura, M and Tamura, M and Kurita, M and Nose, M and Hanaoka, S and Takahashi, M and Watanabe, A}, title = {Identification of novel putative causative genes and genetic marker for male sterility in Japanese cedar (Cryptomeria japonica D.Don).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {277}, pmid = {29685102}, issn = {1471-2164}, support = {JP26850103//JSPS KAKENHI/ ; }, mesh = {Cryptomeria/*genetics/*physiology ; Genes, Plant/*genetics ; Genetic Markers/*genetics ; Genotype ; High-Throughput Nucleotide Sequencing ; Phenotype ; Plant Infertility/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Japanese cedar (Cryptomeria japonica) is an important tree for Japanese forestry. Male-sterile marker development in Japanese cedar would facilitate selection of male-sterile plus trees, addressing the widespread social problem of pollinosis and facilitating the identification of heterozygotes, which are useful for breeding.

RESULTS: This study used next-generation sequencing for single-nucleotide polymorphism discovery in libraries constructed from several organs, including male-sterile and male-fertile strobili. The single-nucleotide polymorphisms obtained were used to construct a high-density linkage map, which enabled identification of a locus on linkage group 9 strongly correlated with male-sterile trait. Expressed sequence tags corresponding to 11 marker loci from 5 isotigs were associated with this locus within 33.4-34.5 cM. These marker loci explained 100% of the phenotypic variation. Several homologs of these sequences are associated with male sterility in rice or Arabidopsis, including a pre-mRNA splicing factor, a DEAD-box protein, a glycosyl hydrolase, and a galactosyltransferase. These proteins are thus candidates for the causal male-sterile gene at the ms-1 locus. After we used a SNaPshot assay to develop markers for marker-assisted selection (MAS), we tested F2 progeny between male-sterile and wild-type plus trees to validate the markers and extrapolated the testing to a larger plus-tree population. We found that two developed from one of the candidates for the causal gene were suitable for MAS.

CONCLUSIONS: More than half of the ESTs and SNPs we collected were new, enlarging the genomic basis for genetic research on Japanese cedar. We developed two SNP markers aimed at MAS that distinguished individuals carrying the male-sterile trait with 100% accuracy, as well as individuals heterozygous at the male-sterile locus, even outside the mapping population. These markers should enable practical MAS for conifer breeding.}, } @article {pmid29685101, year = {2018}, author = {Zhang, X and Lei, L and Lai, J and Zhao, H and Song, W}, title = {Effects of drought stress and water recovery on physiological responses and gene expression in maize seedlings.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {68}, pmid = {29685101}, issn = {1471-2229}, support = {31671698//National Natural Science Foundation of China/ ; 2016YFD0100404//National Key Research & Development Program/ ; 2016YFD0101803//National Key Research & Development Program/ ; 2016YFD0100802//National Key Research & Development Program/ ; }, mesh = {Droughts ; Gene Expression Regulation, Plant/physiology ; Plant Proteins/genetics/metabolism ; Seedlings/*metabolism/*physiology ; Transcription Factors/genetics/metabolism ; Zea mays/*metabolism/*physiology ; }, abstract = {BACKGROUND: Drought is one of the major factors limiting global maize production. Exposure to long-term drought conditions inhibits growth and leads to yield losses. Although several drought-responsive genes have been identified and functionally analyzed, the mechanisms underlying responses to drought and water recovery treatments have not been fully elucidated. To characterize how maize seedling respond to drought stress at the transcriptional level, we analyzed physiological responses and differentially expressed genes (DEGs) in the inbred line B73 under water deficit and recovery conditions.

RESULTS: The data for relative leaf water content, leaf size, and photosynthesis-related parameters indicated that drought stress significantly repressed maize seedling growth. Further RNA sequencing analysis revealed that 6107 DEGs were responsive to drought stress and water recovery, with more down-regulated than up-regulated genes. Among the DEGs, the photosynthesis- and hormone-related genes were enriched in responses to drought stress and re-watering. Additionally, transcription factor genes from 37 families were differentially expressed among the three analyzed time-points. Gene ontology enrichment analyses of the DEGs indicated that 50 GO terms, including those related to photosynthesis, carbohydrate metabolism, oxidoreductase activities, nutrient metabolism and other drought-responsive pathways, were over-represented in the drought-treated seedlings. The content of gibberellin in drought treatment seedlings was decreased compared to that of control seedlings, while abscisic acid showed accumulated in the drought treated plants. The deep analysis of DEGs related to cell wall development indicated that these genes were prone to be down-regulated at drought treatment stage.

CONCLUSIONS: Many genes that are differentially expressed in responses to drought stress and water recovery conditions affect photosynthetic systems and hormone biosynthesis. The identified DEGs, especially those encoding transcription factors, represent potential targets for developing drought-tolerant maize lines.}, } @article {pmid29685100, year = {2018}, author = {Moolhuijzen, P and See, PT and Hane, JK and Shi, G and Liu, Z and Oliver, RP and Moffat, CS}, title = {Comparative genomics of the wheat fungal pathogen Pyrenophora tritici-repentis reveals chromosomal variations and genome plasticity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {279}, pmid = {29685100}, issn = {1471-2164}, support = {COR00023//Grains Research and Development Corporation/ ; }, mesh = {Ascomycota/*genetics/*physiology ; Chromosomes, Fungal/*genetics ; Gene Transfer, Horizontal ; *Genetic Variation ; Genome, Fungal/*genetics ; Genome, Mitochondrial/genetics ; *Genomics ; Molecular Sequence Annotation ; Phylogeny ; Sequence Homology, Nucleic Acid ; Triticum/*microbiology ; }, abstract = {BACKGROUND: Pyrenophora tritici-repentis (Ptr) is a necrotrophic fungal pathogen that causes the major wheat disease, tan spot. We set out to provide essential genomics-based resources in order to better understand the pathogenicity mechanisms of this important pathogen.

RESULTS: Here, we present eight new Ptr isolate genomes, assembled and annotated; representing races 1, 2 and 5, and a new race. We report a high quality Ptr reference genome, sequenced by PacBio technology with Illumina paired-end data support and optical mapping. An estimated 98% of the genome coverage was mapped to 10 chromosomal groups, using a two-enzyme hybrid approach. The final reference genome was 40.9 Mb and contained a total of 13,797 annotated genes, supported by transcriptomic and proteogenomics data sets.

CONCLUSIONS: Whole genome comparative analysis revealed major chromosomal segmental rearrangements and fusions, highlighting intraspecific genome plasticity in this species. Furthermore, the Ptr race classification was not supported at the whole genome level, as phylogenetic analysis did not cluster the ToxA producing isolates. This expansion of available Ptr genomics resources will directly facilitate research aimed at controlling tan spot disease.}, } @article {pmid29685080, year = {2018}, author = {Kramer, RSS and Mulgrew, J}, title = {Displaying Red and Black on a First Date: A Field Study Using the "First Dates" Television Series.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {2}, pages = {1474704918769417}, doi = {10.1177/1474704918769417}, pmid = {29685080}, issn = {1474-7049}, mesh = {Adult ; Clothing/*psychology ; *Color ; Courtship/*psychology ; Female ; Humans ; Male ; Middle Aged ; Sexual Behavior/*psychology ; Young Adult ; }, abstract = {Previous research has shown that displaying the color red can increase attractiveness. As a result, women display red more often when expecting to meet more attractive men in a laboratory context. Here, we carried out a field study by analyzing 546 daters from the "First Dates" television series. Each participant was filmed in a pre-date interview and during a real first date, allowing direct comparison of the clothing worn by each person in these two contexts. Analysis of ratings of the amount of red displayed showed that both men and women wore more red clothing during their dates. This pattern was even stronger for black clothing, while the amount of blue clothing did not differ across the two contexts. Our results provide the first real-world demonstration that people display more red and black clothing when meeting a possible mate for the first time, perhaps seeking to increase their attractiveness and/or reveal their intentions to potential partners.}, } @article {pmid29684598, year = {2018}, author = {Aouad, M and Taib, N and Oudart, A and Lecocq, M and Gouy, M and Brochier-Armanet, C}, title = {Extreme halophilic archaea derive from two distinct methanogen Class II lineages.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {46-54}, doi = {10.1016/j.ympev.2018.04.011}, pmid = {29684598}, issn = {1095-9513}, abstract = {Phylogenetic analyses of conserved core genes have disentangled most of the ancient relationships in Archaea. However, some groups remain debated, like the DPANN, a deep-branching super-phylum composed of nanosized archaea with reduced genomes. Among these, the Nanohaloarchaea require high-salt concentrations for growth. Their discovery in 2012 was significant because they represent, together with Halobacteria (a Class belonging to Euryarchaeota), the only two described lineages of extreme halophilic archaea. The phylogenetic position of Nanohaloarchaea is highly debated, being alternatively proposed as the sister-lineage of Halobacteria or a member of the DPANN super-phylum. Pinpointing the phylogenetic position of extreme halophilic archaea is important to improve our knowledge of the deep evolutionary history of Archaea and the molecular adaptive processes and evolutionary paths that allowed their emergence. Using comparative genomic approaches, we identified 258 markers carrying a reliable phylogenetic signal. By combining strategies limiting the impact of biases on phylogenetic inference, we showed that Nanohaloarchaea and Halobacteria represent two independent lines that derived from two distinct but related methanogen Class II lineages. This implies that adaptation to high salinity emerged twice independently in Archaea and indicates that emergence of Nanohaloarchaea within DPANN in previous studies is likely the consequence of a tree reconstruction artifact, challenging the existence of this super-phylum.}, } @article {pmid29684597, year = {2018}, author = {Su, Y and Huang, L and Wang, Z and Wang, T}, title = {Comparative chloroplast genomics between the invasive weed Mikania micrantha and its indigenous congener Mikania cordata: Structure variation, identification of highly divergent regions, divergence time estimation, and phylogenetic analysis.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {181-195}, doi = {10.1016/j.ympev.2018.04.015}, pmid = {29684597}, issn = {1095-9513}, mesh = {Asteraceae/genetics ; China ; Chloroplasts ; Chromosome Mapping ; *Genome, Chloroplast ; *Genomics ; *Introduced Species ; Microsatellite Repeats/genetics ; Mikania/*classification/*genetics ; Mutation/genetics ; Open Reading Frames/genetics ; *Phylogeny ; Plant Weeds/*classification/*genetics ; Sequence Analysis, DNA ; Time Factors ; }, abstract = {Mikania micrantha and Mikania cordata are the only two species in genus Mikania (Asteraceae) in China. They share very similar morphological and life-history characteristics but occupy quite different habitats. Most importantly, they generate totally different ecological consequences. While M. micrantha has become an exotic invasive weed, M. cordata exists as an indigenous species with no harmful effects on native plants or habitats. As a continuous study of our previously reported M. micrantha chloroplast (cp) genome, in this study we have further sequenced the M. cordata cp genome to (1) conduct a comparative genome analysis to gain insights into the mechanism of invasiveness; (2) develop cp markers to examine the population genetic adaptation of M. micrantha; and (3) screen variable genome regions of phylogenetic utility. The M. cordata chloroplast genome is 151,984 bp in length and displays a typical quadripartite structure. The number and distribution of protein coding genes, tRNA genes, and rRNA genes of M. cordata are identical to those of M. micrantha. The main difference lays in that the pseudogenization of ndhF and a 118-bp palindromic repeat only arises in M. cordata. Fourteen highly divergent regions, 235 base substitutions, and 58 indels were identified between the two cp genomes. Phylogenetic inferences revealed a sister relationship between M. micrantha and M. cordata whose divergence was estimated to occur around 1.78 million years ago (MYA). Twelve cpSSR loci were detected to be polymorphic and adopted to survey the genetic adaptation of M. micrantha populations. No cpSSR loci were found to undergo selection. Our results build a foundation to examine the invasive mechanism of Mikania weed.}, } @article {pmid29684596, year = {2018}, author = {Qasim, M and Baohua, W and Zou, H and Lin, Y and Dash, CK and Bamisile, BS and Hussain, M and Zhiwen, Z and Wang, L}, title = {Phylogenetic relationship and genetic diversity of citrus psyllid populations from China and Pakistan and their associated Candidatus bacterium.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {173-180}, doi = {10.1016/j.ympev.2018.04.028}, pmid = {29684596}, issn = {1095-9513}, mesh = {Animals ; China ; Citrus/*parasitology ; Genes, Insect ; *Genetic Variation ; Haplotypes/genetics ; Hemiptera/classification/*genetics/*microbiology ; Likelihood Functions ; Pakistan ; *Phylogeny ; Plant Diseases/parasitology ; RNA, Ribosomal, 16S/genetics ; Rhizobiaceae/*physiology ; }, abstract = {Asian citrus psyllid (ACP), Diaphorina citri Kuwayama (Hemiptera: Liviidae), is a severely devastating pest of Rutaceae plants, mainly citrus, across the globe, and causal agent of Huanglongbing (HLB) disease. To find out the genetic relationship and diversity among the populations of ACP and associated Candidatus Liberibacter asiaticus (CLas) from two countries (China and Pakistan), sequence data of three different genes, cytochrome oxidase subunit I (COI), Cu-transporting protein (ATOX1) and 16S rRNA, were used to characterize all populations. In the present study, MEGA-7 and statistical parsimony software (TCS-1.2) were used to depict the phylogenetic relationship among all populations under both genes, whereas diversity was calculated by DnaSP v5. All analyses were done for country wise and overall relationship among all populations. For ACP populations, both genes presented a significant strong intermingled relationship among all populations and put all population into a single haplotype (Dcit-2), which proved similarity between Chinese and Pakistani populations. Moreover, for CLas strains, 16S gene also presented strong relationship for all sampled populations. All three genes of ACP and CLas populations elucidated more than 95% resemblance to each other. On the other hand, a significant genetic variation was observed by three genes for overall populations, although, country wise variation was non-significant between all collected populations. ATOX1 gene presented higher diversity through Fu's Fs test (π = 0.01081, p < 0.003) whereas COI gene gave less diversity under Fu's Fs and Tajima's D test (π = 0.00512, p < 0.000 and 0.05, respectively). Similarly, nucleotide mismatch distribution also had shown enough genetic variation among all ACP populations, under both genes. Our sequence data for both genes proved the invasion of the Chinese ACP population (Dcit-2) into Pakistan, through all phylogenetic relationship, which proved a similar genetic makeup among all ACP populations from both countries. Therefore, these results can be helpful to utilize any novel designed control measure equally for both countries.}, } @article {pmid29684312, year = {2018}, author = {Rohner, N}, title = {Cavefish as an evolutionary mutant model system for human disease.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {355-357}, doi = {10.1016/j.ydbio.2018.04.013}, pmid = {29684312}, issn = {1095-564X}, mesh = {Animals ; *Characiformes/genetics/metabolism ; *Disease Models, Animal ; *Evolution, Molecular ; *Eye Diseases, Hereditary/genetics/metabolism ; Humans ; *Mutation ; }, } @article {pmid29684311, year = {2018}, author = {Srivillibhuthur, M and Warder, BN and Toke, NH and Shah, PP and Feng, Q and Gao, N and Bonder, EM and Verzi, MP}, title = {TFAM is required for maturation of the fetal and adult intestinal epithelium.}, journal = {Developmental biology}, volume = {439}, number = {2}, pages = {92-101}, pmid = {29684311}, issn = {1095-564X}, support = {R01 DK102934/DK/NIDDK NIH HHS/United States ; R03 DK099251/DK/NIDDK NIH HHS/United States ; U01 DK103141/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Culture Techniques/methods ; Cell Self Renewal/physiology ; DNA-Binding Proteins/genetics/*metabolism/*physiology ; Fetus/metabolism ; Gene Expression Regulation/genetics ; Glycolysis/genetics/physiology ; High Mobility Group Proteins/genetics/*metabolism/*physiology ; Intestinal Mucosa/embryology/growth & development/*metabolism ; Mice ; Mitochondria/metabolism ; Mitochondrial Proteins/genetics ; Organogenesis/genetics/physiology ; Organoids/metabolism ; Stem Cells/metabolism ; Transcription Factors/metabolism ; }, abstract = {During development, the embryo transitions from a metabolism favoring glycolysis to a metabolism favoring mitochondrial respiration. How metabolic shifts regulate developmental processes, or how developmental processes regulate metabolic shifts, remains unclear. To test the requirement of mitochondrial function in developing endoderm-derived tissues, we genetically inactivated the mitochondrial transcription factor, Tfam, using the Shh-Cre driver. Tfam mutants did not survive postnatally, exhibiting defects in lung development. In the developing intestine, TFAM-loss was tolerated until late fetal development, during which the process of villus elongation was compromised. While progenitor cell populations appeared unperturbed, markers of enterocyte maturation were diminished and villi were blunted. Loss of TFAM was also tested in the adult intestinal epithelium, where enterocyte maturation was similarly dependent upon the mitochondrial transcription factor. While progenitor cells in the transit amplifying zone of the adult intestine remained proliferative, intestinal stem cell renewal was dependent upon TFAM, as indicated by molecular profiling and intestinal organoid formation assays. Taken together, these studies point to critical roles for the mitochondrial regulator TFAM for multiple aspects of intestinal development and maturation, and highlight the importance of mitochondrial regulators in tissue development and homeostasis.}, } @article {pmid29684203, year = {2018}, author = {Malmstrøm, M and Britz, R and Matschiner, M and Tørresen, OK and Hadiaty, RK and Yaakob, N and Tan, HH and Jakobsen, KS and Salzburger, W and Rüber, L}, title = {The Most Developmentally Truncated Fishes Show Extensive Hox Gene Loss and Miniaturized Genomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1088-1103}, pmid = {29684203}, issn = {1759-6653}, mesh = {Animals ; Body Size/genetics ; Cyprinidae/anatomy & histology/genetics ; *Evolution, Molecular ; Genes, Homeobox/*genetics ; Genome/*genetics ; *Phylogeny ; Zebrafish/genetics ; }, abstract = {The world's smallest fishes belong to the genus Paedocypris. These miniature fishes are endemic to an extreme habitat: the peat swamp forests in Southeast Asia, characterized by highly acidic blackwater. This threatened habitat is home to a large array of fishes, including a number of miniaturized but also developmentally truncated species. Especially the genus Paedocypris is characterized by profound, organism-wide developmental truncation, resulting in sexually mature individuals of <8 mm in length with a larval phenotype. Here, we report on evolutionary simplification in the genomes of two species of the dwarf minnow genus Paedocypris using whole-genome sequencing. The two species feature unprecedented Hox gene loss and genome reduction in association with their massive developmental truncation. We also show how other genes involved in the development of musculature, nervous system, and skeleton have been lost in Paedocypris, mirroring its highly progenetic phenotype. Further, our analyses suggest two mechanisms responsible for the genome streamlining in Paedocypris in relation to other Cypriniformes: severe intron shortening and reduced repeat content. As the first report on the genomic sequence of a vertebrate species with organism-wide developmental truncation, the results of our work enhance our understanding of genome evolution and how genotypes are translated to phenotypes. In addition, as a naturally simplified system closely related to zebrafish, Paedocypris provides novel insights into vertebrate development.}, } @article {pmid29684198, year = {2018}, author = {Cannataro, VL and Townsend, JP}, title = {Neutral Theory and the Somatic Evolution of Cancer.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1308-1315}, pmid = {29684198}, issn = {1537-1719}, support = {R01 LM012487/LM/NLM NIH HHS/United States ; }, abstract = {Kimura's neutral theory argued that positive selection was not responsible for an appreciable fraction of molecular substitutions. Correspondingly, quantitative analysis reveals that the vast majority of substitutions in cancer genomes are not detectably under selection. Insights from the somatic evolution of cancer reveal that beneficial substitutions in cancer constitute a small but important fraction of the molecular variants. The molecular evolution of cancer community will benefit by incorporating the neutral theory of molecular evolution into their understanding and analysis of cancer evolution-and accepting the use of tractable, predictive models, even when there is some evidence that they are not perfect.}, } @article {pmid29684183, year = {2018}, author = {Rocha, EPC}, title = {Neutral Theory, Microbial Practice: Challenges in Bacterial Population Genetics.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1338-1347}, doi = {10.1093/molbev/msy078}, pmid = {29684183}, issn = {1537-1719}, abstract = {I detail four major open problems in microbial population genetics with direct implications to the study of molecular evolution: the lack of neutral polymorphism, the modeling of promiscuous genetic exchanges, the genetics of ill-defined populations, and the difficulty of untangling selection and demography in the light of these issues. Together with the historical focus on the study of single nucleotide polymorphism and widespread non-random sampling, these problems limit our understanding of the genetic variation in bacterial populations and their adaptive effects. I argue that we need novel theoretical approaches accounting for pervasive selection and strong genetic linkage to better understand microbial evolution.}, } @article {pmid29684170, year = {2018}, author = {Kelly, S}, title = {The Amount of Nitrogen Used for Photosynthesis Modulates Molecular Evolution in Plants.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1616-1625}, pmid = {29684170}, issn = {1537-1719}, abstract = {Genome and transcript sequences are composed of long strings of nucleotide monomers (A, C, G, and T/U) that require different quantities of nitrogen atoms for biosynthesis. Here, it is shown that the strength of selection acting on transcript nitrogen content is influenced by the amount of nitrogen plants require to conduct photosynthesis. Specifically, plants that require more nitrogen to conduct photosynthesis experience stronger selection on transcript sequences to use synonymous codons that cost less nitrogen to biosynthesize. It is further shown that the strength of selection acting on transcript nitrogen cost constrains molecular sequence evolution such that genes experiencing stronger selection evolve at a slower rate. Together these findings reveal that the plant molecular clock is set by photosynthetic efficiency, and provide a mechanistic explanation for changes in plant speciation rates that occur concomitant with improvements in photosynthetic efficiency and changes in the environment such as light, temperature, and atmospheric CO2 concentration.}, } @article {pmid29684163, year = {2018}, author = {Huang, CJ and Lu, MY and Chang, YW and Li, WH}, title = {Experimental Evolution of Yeast for High-Temperature Tolerance.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1823-1839}, doi = {10.1093/molbev/msy077}, pmid = {29684163}, issn = {1537-1719}, abstract = {Thermotolerance is a polygenic trait that contributes to cell survival and growth under unusually high temperatures. Although some genes associated with high-temperature growth (Htg+) have been identified, how cells accumulate mutations to achieve prolonged thermotolerance is still mysterious. Here, we conducted experimental evolution of a Saccharomyces cerevisiae laboratory strain with stepwise temperature increases for it to grow at 42 °C. Whole genome resequencing of 14 evolved strains and the parental strain revealed a total of 153 mutations in the evolved strains, including single nucleotide variants, small INDELs, and segmental duplication/deletion events. Some mutations persisted from an intermediate temperature to 42 °C, so they might be Htg+ mutations. Functional categorization of mutations revealed enrichment of exonic mutations in the SWI/SNF complex and F-type ATPase, pointing to their involvement in high-temperature tolerance. In addition, multiple mutations were found in a general stress-associated signal transduction network consisting of Hog1 mediated pathway, RAS-cAMP pathway, and Rho1-Pkc1 mediated cell wall integrity pathway, implying that cells can achieve Htg+ partly through modifying existing stress regulatory mechanisms. Using pooled segregant analysis of five Htg+ phenotype-orientated pools, we inferred causative mutations for growth at 42 °C and identified those mutations with stronger impacts on the phenotype. Finally, we experimentally validated a number of the candidate Htg+ mutations. This study increased our understanding of the genetic basis of yeast tolerance to high temperature.}, } @article {pmid29684129, year = {2018}, author = {Clouet-d'Orval, B and Batista, M and Bouvier, M and Quentin, Y and Fichant, G and Marchfelder, A and Maier, LK}, title = {Insights into RNA-processing pathways and associated RNA-degrading enzymes in Archaea.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {5}, pages = {579-613}, doi = {10.1093/femsre/fuy016}, pmid = {29684129}, issn = {1574-6976}, mesh = {Archaea/*enzymology/metabolism ; Endoribonucleases/*metabolism ; Exoribonucleases/*metabolism ; RNA Processing, Post-Transcriptional/*physiology ; }, abstract = {RNA-processing pathways are at the centre of regulation of gene expression. All RNA transcripts undergo multiple maturation steps in addition to covalent chemical modifications to become functional in the cell. This includes destroying unnecessary or defective cellular RNAs. In Archaea, information on mechanisms by which RNA species reach their mature forms and associated RNA-modifying enzymes are still fragmentary. To date, most archaeal actors and pathways have been proposed in light of information gathered from Bacteria and Eukarya. In this context, this review provides a state of the art overview of archaeal endoribonucleases and exoribonucleases that cleave and trim RNA species and also of the key small archaeal proteins that bind RNAs. Furthermore, synthetic up-to-date views of processing and biogenesis pathways of archaeal transfer and ribosomal RNAs as well as of maturation of stable small non-coding RNAs such as CRISPR RNAs, small C/D and H/ACA box guide RNAs, and other emerging classes of small RNAs are described. Finally, prospective post-transcriptional mechanisms to control archaeal messenger RNA quality and quantity are discussed.}, } @article {pmid29683420, year = {2018}, author = {Wang, NN and Liu, ZY and Jiang, LX and Li, YX and Du, ZJ}, title = {Roseovarius salinarum sp. nov., isolated from a marine solar saltern.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1986-1991}, doi = {10.1099/ijsem.0.002778}, pmid = {29683420}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; *Salinity ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Water Microbiology ; }, abstract = {A Gram-stain-negative, rod-shaped, non-motile and halophilic bacterium, designated N53T, was isolated from a marine solar saltern in Wendeng, China. Cells of strain N53T were 0.3-0.4 µm wide and 2.0-5.5 µm long, catalase-positive and oxidase-positive. The bacterium grew optimally at 33 °C, at pH 7.0-8.0 and in the presence of 6.0 % (w/v) NaCl. Bacteriochlorophyll a was not found. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain N53T formed a phylogenetic lineage with members of the genus Roseovarius. Strain N53T exhibited the highest levels of similarity to Roseovarius pacificus (94.6 %) and Roseovarius confluentis (94.6 %), with a lower level to Roseovarius tolerans was 94.0 %. The percentage of conserved proteins and average nucleotide identity values between N53T and the type strain of the type species, Roseovarius tolerans, were 66.1 and 76.4 %, respectively. The genomic DNA G+C content was 68.1 mol%. The sole respiratory quinone was ubiquinone-10. The predominant cellular fatty acids (>10 %) were C18 : 1ω7c (54.0 %) and C16 : 0 (17.9 %). The polar lipids of strain N53T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, an unidentified aminolipid, two unidentified phospholipids and two unidentified glycolipids. The differential phenotypic properties, together with the chemotaxonomic and genomic distinctiveness, revealed that strain N53T was separate from other recognized species of the genus Roseovarius. On the basis of the data presented here, strain N53T represents a novel species of the genus Roseovarius, for which the name Roseovariussalinarum sp. nov. is proposed. The type strain is N53T (=MCCC 1H00200T=KCTC 52886T).}, } @article {pmid29683418, year = {2018}, author = {Yan, ZF and Lin, P and Li, CT and Kook, M and Yi, TH}, title = {Nocardioides pelophilus sp. nov., isolated from freshwater mud.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1942-1948}, doi = {10.1099/ijsem.0.002776}, pmid = {29683418}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Fresh Water ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, aerobic, motile, rod- or cocci-shaped bacterium with flagella bacterium (THG-T63T) was isolated from freshwater mud. Growth occurred at 10-40 °C (optimum, 28-35 °C), at pH 6-8 (optimum, 7) and at 0-6 % NaCl (optimum, 2 %). Based on 16S rRNA sequence analysis, the nearest phylogenetic neighbours of strain THG-T63T were identified as Nocardioides panacisoli KCTC 19470T (97.5 %), Nocardioides caeni KCTC 19600T (96.4 %), Nocardioides humi KCTC 19265T (96.3 %), Nocardioides kongjuensis KCTC 19054T (96.1 %) and Nocardioides nitrophenolicus KCTC 457BPT (96.1 %). 16S rRNA sequence similarities among strain THG-T63T and other species were lower than 96.0 %. The polar lipids were phosphatidylglycerol, phosphatidylinositol and one unidentified phospholipid. The quinone system was composed of MK-8 (H4). The major fatty acids were C16 : 0, C17 : 1ω6c, C17 : 1ω8c, C18 : 0 10-methyl, C18 : 1ω9c and iso-C16 : 0. The cell-wall peptidoglycan contained ll-2,6-diaminopimelic acid. The DNA G+C content of strain THG-T63T was 74.6 mol%. Strain THG-T63T exhibited levels of DNA-DNA relatedness of 20-44 % to the type strains of phylogenetically related Nocardioides species and could be differentiated from these species based on differences in phenotypic characteristics. On the basis of the data presented here, strain THG-T63T represents a novel species of the genus Nocardioides, for which the name Nocardioides pelophilus sp. nov. is proposed. The type strain is THG-T63T(=KACC 19192T=CGMCC 4.7388T).}, } @article {pmid29683417, year = {2018}, author = {Castejon, M and Menéndez, MC and Comas, I and Vicente, A and Garcia, MJ}, title = {Whole-genome sequence analysis of the Mycobacterium avium complex and proposal of the transfer of Mycobacterium yongonense to Mycobacterium intracellulare subsp. yongonense subsp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1998-2005}, doi = {10.1099/ijsem.0.002767}, pmid = {29683417}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; *Genome, Bacterial ; Mycobacterium avium Complex/*classification/genetics ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Bacterial whole-genome sequences contain informative features of their evolutionary pathways. Comparison of whole-genome sequences have become the method of choice for classification of prokaryotes, thus allowing the identification of bacteria from an evolutionary perspective, and providing data to resolve some current controversies. Currently, controversy exists about the assignment of members of the Mycobacterium avium complex, as is for the cases of Mycobacterium yongonense and 'Mycobacterium indicus pranii'. These two mycobacteria, closely related to Mycobacterium intracellulare on the basis of standard phenotypic and single gene-sequences comparisons, were not considered a member of such species on the basis on some particular differences displayed by a single strain. Whole-genome sequence comparison procedures, namely the average nucleotide identity and the genome distance, showed that those two mycobacteria should be considered members of the species M. intracellulare. The results were confirmed with other whole-genome comparison supplementary methods. According to the data provided, Mycobacterium yongonense and 'Mycobacterium indicus pranii' should be considered and renamed and included as members of M. intracellulare. This study highlights the problems caused when a novel species is accepted on the basis of a single strain, as was the case for M. yongonense. Based mainly on whole-genome sequence analysis, we conclude that M. yongonense should be reclassified as a subspecies of Mycobacterium intracellulareas Mycobacterium intracellularesubsp. yongonense and 'Mycobacterium indicus pranii' classified in the same subspecies as the type strain of Mycobacterium intracellulare and classified as Mycobacterium intracellularesubsp. intracellulare.}, } @article {pmid29683416, year = {2018}, author = {Liu, KF and Li, XH and Hui, FL}, title = {Yarrowia brassicae f.a., sp. nov., a new yeast species from traditional Chinese sauerkraut.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2024-2027}, doi = {10.1099/ijsem.0.002783}, pmid = {29683416}, issn = {1466-5034}, mesh = {China ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Fermented Foods/*microbiology ; Mycological Typing Techniques ; *Phylogeny ; Sequence Analysis, DNA ; Spores, Fungal ; Yarrowia/*classification/genetics/isolation & purification ; }, abstract = {Two strains of a novel yeast species were isolated from traditional Chinese sauerkraut samples collected in Nanyang, Henan Province, central China. Phylogenetic analysis based on the concatenated sequences of the D1/D2 domains of the large subunit rRNA gene and the internal transcribed spacer (ITS) regions showed that these strains belong to the Yarrowia clade, with seven clones of uncultured Yarrowia as their closest phylogenetic neighbours. They differed from their closest known species, Yarrowia divulgata CBS 11013T, by 3.2 % sequence divergence (14 substitutions and 2 gaps) in the D1/D2 domains and by 5.4 % sequence divergence (12 substitutions and 5 gaps) in the ITS regions. The two strains of novel species reproduced asexually, and no ascospores could be found. The name Yarrowia brassicae f.a., sp. nov. is proposed to accommodate these strains, with NYNU 17218T (=CICC 33263T=CBS 15225T) as the type strain.}, } @article {pmid29683415, year = {2018}, author = {Gao, Y and Piao, C and Wang, H and Shi, L and Guo, X and Song, J and Xiang, W and Zhao, J and Wang, X}, title = {Pseudonocardia lutea sp. nov., a novel actinobacterium isolated from soil in Chad.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1992-1997}, doi = {10.1099/ijsem.0.002780}, pmid = {29683415}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; Chad ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/analysis ; Geologic Sediments/*microbiology ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rivers ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, designated strain NEAU-G57T was isolated from a soil sample collected from the bottom of a river in Chad. A polyphasic approach was employed to determine the status of strain NEAU-G57T. Phylogenetic analysis based on its 16S rRNA gene sequence indicated that the organism should be assigned to the genus Pseudonocardia and formed a monophyletic clade with its closest relatives Pseudonocardia yuanmoensis YIM 75926T (98.8 %), Pseudonocardia halophobica DSM 43089T (98.2 %) and Pseudonocardia kujensis A 4038T (97.6 %). Moreover, morphological and chemotaxonomic properties of strain NEAU-G57T also confirmed the affiliation of the isolate to the genus Pseudonocardia. The cell wall contained meso-diaminopimelic acid and whole-cell sugars were glucose, xylose, arabinose and galactose. The predominant menaquinone was MK-8(H4). The phospholipid profile consisted of diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, hydroxyphosphatidylmethylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol mannosides, one unidentified glycolipid and one unidentified lipid. The major fatty acids were C16 : 0 and C16 : 1ω7c. The DNA G+C content was 73.3 mol%. However, the low level of DNA-DNA relatedness and some phenotypic characteristics allowed the isolate to be differentiated from its closely related species. Therefore, it is concluded that strain NEAU-G57T can be classified as representing a novel species of the genus Pseudonocardia, for which the name Pseudonocardia lutea sp. nov. is proposed. The type strain is NEAU-G57T (=JCM 32387T=CGMCC 4.7397T).}, } @article {pmid29683414, year = {2018}, author = {Dahal, RH and Chaudhary, DK and Kim, J}, title = {Pinisolibacter ravus gen. nov., sp. nov., isolated from pine forest soil and allocation of the genera Ancalomicrobium and Pinisolibacter to the family Ancalomicrobiaceae fam. nov., and emendation of the genus Ancalomicrobium Staley 1968.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1955-1962}, doi = {10.1099/ijsem.0.002772}, pmid = {29683414}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Phospholipids/chemistry ; *Phylogeny ; *Pinus ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A novel bacterium, designated strain E9T, was isolated from pine forest soil of Kyonggi University (Suwon, Republic of Korea). Cells were facultatively anaerobic, Gram-staining-negative, catalase-negative, oxidase-positive, non-motile, non-spore-forming, rod-shaped and straw coloured. Prosthecae were absent. Glucose was fermented. The strain grew in the pH range of 5.0-10.0 (optimum, 6.5-8.5) and at 45 °C (optimum, 28-32 °C). E9T was sensitive to NaCl at low concentration and tolerated only 0.2 % NaCl (w/v). A phylogenetic analysis based on 16S rRNA gene sequences revealed that E9T formed a lineage within the phylum Proteobacteria that was distinct from various members of the order Rhizobiales, including Ancalomicrobium adetum DSM 4722T (94.76 % sequence similarity), 'Nitratireductor lucknowense' IITR-21 (92.72 %), Prosthecomicrobium hirschii 16T (92.66 %) and Kaistia soli DSM 19436T (92.53 %). The predominant isoprenoid quinone was Q-10. The major polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol and phosphatidyl-N-methylethanolamine. Major cellular fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), and C16 : 0. The DNA G+C content of the type strain was 68.4 mol%. Polyphasic characterization indicated that strain E9T represented a novel species in a novel genus within a novel family, for which the name Pinisolibacter ravus gen. nov., sp. nov. is proposed. The type strain of Pinisolibacter ravus is E9T (=KEMB 9005-534T=KACC 19120T=NBRC 112686T). A formal allocation of the genus Ancalomicrobium to the family Ancalomicrobiaceae fam. nov. is also proposed.}, } @article {pmid29682883, year = {2018}, author = {Pocherniaieva, K and Sidova, M and Havelka, M and Saito, T and Psenicka, M and Sindelka, R and Kaspar, V}, title = {Comparison of oocyte mRNA localization patterns in sterlet Acipenser ruthenus and African clawed frog Xenopus laevis.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {3}, pages = {181-187}, doi = {10.1002/jez.b.22802}, pmid = {29682883}, issn = {1552-5015}, mesh = {Animals ; Biological Evolution ; *Fishes ; Oocytes/*physiology ; Protein Transport/*physiology ; RNA, Messenger/*physiology ; Species Specificity ; *Xenopus ; }, abstract = {In oocytes, RNA localization has critical implications, as assembly of proteins in particular subcellular domains is crucial to embryo development. The distribution of mRNA molecules can identify and characterize localized transcripts. The goal of this study was to clarify the origin of primordial germ cells in the oocyte body plan and to reveal the generation of cell lineages by localized RNAs. The distribution of 12 selected mRNAs in sterlet Acipenser ruthenus oocytes was investigated by qPCR tomography and compared with known patterns of mRNA localization in Xenopus laevis. We investigated the distribution of two gene clusters in the ooplasm along the animal-vegetal axis of the sturgeon oocyte, both of which showed clearly defined intracellular gradient pattern remarkably similar to their distribution in the frog oocyte. We elucidated the localization of sturgeon egg germplasm markers belonging to the vegetal group of mRNAs. The mRNAs coding otx1, wnt11, and veg1 found to be localized in the sturgeon animal hemisphere are, in contrast, distributed in the vegetal hemisphere in amphibian. Actinopterygii and Sarcopterygii, two major lineages of osteichthyan vertebrates, split about 476 Ma (Blair & Hedges,), albeit basal lineages share conserved biological features. Acipenseriformes is one the most basal living lineages of Actinopterygii, having evolved about 200 Ma (Bemis, Birstein, & Waldman,), contemporaneous with modern amphibians (Roelants et al.,).}, } @article {pmid29682730, year = {2018}, author = {Adams, DC and Collyer, ML}, title = {Phylogenetic ANOVA: Group-clade aggregation, biological challenges, and a refined permutation procedure.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1204-1215}, doi = {10.1111/evo.13492}, pmid = {29682730}, issn = {1558-5646}, abstract = {Phylogenetic regression is frequently used in macroevolutionary studies, and its statistical properties have been thoroughly investigated. By contrast, phylogenetic ANOVA has received relatively less attention, and the conditions leading to incorrect statistical and biological inferences when comparing multivariate phenotypes among groups remain underexplored. Here, we propose a refined method of randomizing residuals in a permutation procedure (RRPP) for evaluating phenotypic differences among groups while conditioning the data on the phylogeny. We show that RRPP displays appropriate statistical properties for both phylogenetic ANOVA and regression models, and for univariate and multivariate datasets. For ANOVA, we find that RRPP exhibits higher statistical power than methods utilizing phylogenetic simulation. Additionally, we investigate how group dispersion across the phylogeny affects inferences, and reveal that highly aggregated groups generate strong and significant correlations with the phylogeny, which reduce statistical power and subsequently affect biological interpretations. We discuss the broader implications of this phylogenetic group aggregation, and its relation to challenges encountered with other comparative methods where one or a few transitions in discrete traits are observed on the phylogeny. Finally, we recommend that phylogenetic comparative studies of continuous trait data use RRPP for assessing the significance of indicator variables as sources of trait variation.}, } @article {pmid29682632, year = {2018}, author = {Krapf, P and Russo, L and Arthofer, W and Möst, M and Steiner, FM and Schlick-Steiner, BC}, title = {An Alpine ant's behavioural polymorphism: monogyny with and without internest aggression in Tetramorium alpestre.}, journal = {Ethology, ecology & evolution}, volume = {30}, number = {3}, pages = {220-234}, pmid = {29682632}, issn = {0394-9370}, abstract = {Social structure influences animal societies on various levels (e.g., relatedness, behaviour). In ants, both the number of matings per queen and the number of queens per colony can vary strongly. While workers from both monogynous and polygynous colonies often fight fiercely, in supercolonies (an extreme form of polygyny comprising thousands of queens in spatially separated but interconnected nests), non-nestmates interact peacefully. Studies on social and behavioural polymorphism within ant species can help elucidate their influence on genetic diversity and behaviour and the factors triggering variation in social structure and behaviour. Here, we reveal a behavioural and social polymorphism comprising monogyny with and without internest aggression in Tetramorium alpestre sampled in Tyrol, Austria. The social polymorphism is based on genetic and behavioural evidence and contrasts with the supercolonial organisation known from another location in Austria (Carinthia), 150 km away. Microsatellite genotyping using eight polymorphic loci revealed monogyny-monandry and high intranest pairwise relatedness. Interestingly, various experimental one-on-one worker encounters revealed only occasional aggressive behaviour between monogynous colonies, and thus a behavioural polymorphism. Mantel tests revealed a significant negative correlation between spatial distance and relatedness, while worker behaviour was not correlated with relatedness or spatial distance. These results indicate that behaviour might be influenced by other factors - for example, the experience of workers, ecological, chemical, and/or genetic factors not characterised in this study. However, workers distinguished nestmates from non-nestmates also when aggression was lacking. We hypothesise an adaptive value of reduced aggression. We speculate that the non-aggressive and partly aggressive encounters observed represent different options in the social structure of T. alpestre, the non-aggressiveness possibly also promoting supercolony development. The social and behavioural polymorphisms observed offer opportunities to identify the factors triggering these changes and thus further explore the behavioural and social polymorphism of this ant species.}, } @article {pmid29682170, year = {2018}, author = {Weitzman, CL and Tillett, RL and Sandmeier, FC and Tracy, CR and Alvarez-Ponce, D}, title = {High quality draft genome sequence of Mycoplasma testudineum strain BH29T, isolated from the respiratory tract of a desert tortoise.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {9}, pmid = {29682170}, issn = {1944-3277}, abstract = {Mycoplasma testudineum is one of the pathogens that can cause upper respiratory tract disease in desert tortoises, Gopherus agassizii. We sequenced the genome of M. testudineum BH29T (ATCC 700618T = MCCM 03231T), isolated from the upper respiratory tract of a Mojave desert tortoise with upper respiratory tract disease. The sequenced draft genome, organized in 25 scaffolds, has a length of 960,895 bp and a G + C content of 27.54%. A total of 788 protein-coding sequences, six pseudogenes and 35 RNA genes were identified. The potential presence of cytadhesin-encoding genes is investigated. This genome will enable comparative genomic studies to help understand the molecular bases of the pathogenicity of this and other Mycoplasma species.}, } @article {pmid29682169, year = {2018}, author = {Beye, M and Bakour, S and Traore, SI and Rathored, J and Labas, N and Raoult, D and Fournier, PE}, title = {Draft genome sequence of Fermentimonas caenicola strain SIT8, isolated from the human gut.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {8}, pmid = {29682169}, issn = {1944-3277}, abstract = {We report the properties of a draft genome sequence of the bacterium Fermentimonas caenicola strain SIT8 (= CSUR P1560). This strain, whose genome is described here, was isolated from the fecal flora of a healthy 28-month-old Senegalese boy. Strain SIT8 is a facultatively anaerobic Gram-negative bacillus. Here we describe the features of this organism, together with the complete genome sequence and annotation. The 2,824,451-bp long (1 chromosome but no plasmid) contains 2354 protein-coding and 46 RNA genes, including four rRNA genes.}, } @article {pmid29682168, year = {2018}, author = {Bakenhus, I and Voget, S and Poehlein, A and Brinkhoff, T and Daniel, R and Simon, M}, title = {Genome sequence of Planktotalea frisia type strain (SH6-1T), a representative of the Roseobacter group isolated from the North Sea during a phytoplankton bloom.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {7}, pmid = {29682168}, issn = {1944-3277}, abstract = {Planktotalea frisia SH6-1T Hahnke et al. (Int J Syst Evol Microbiol 62:1619-24, 2012) is a planktonic marine bacterium isolated during a phytoplankton bloom from the southern North Sea. It belongs to the Roseobacter group within the alphaproteobacterial family Rhodobacteraceae. Here we describe the draft genome sequence and annotation of the type strain SH6-1T. The genome comprises 4,106,736 bp and contains 4128 protein-coding and 38 RNA genes. The draft genome sequence provides evidence for at least three extrachromosomal elements, encodes genes for DMSP utilization, quorum sensing, photoheterotrophy and a type IV secretion system. This indicates not only adaptation to a free-living lifestyle of P. frisia but points also to interactions with prokaryotic or eukaryotic organisms.}, } @article {pmid29682167, year = {2018}, author = {Walczak, AB and Yee, N and Young, LY}, title = {Draft genome sequence of Bosea sp. WAO an arsenite and sulfide oxidizer isolated from a pyrite rock outcrop in New Jersey.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {6}, pmid = {29682167}, issn = {1944-3277}, abstract = {This genome report describes the draft genome and physiological characteristics of Bosea sp. WAO (=DSM 102914), a novel strain of the genus Bosea in the family Bradyrhizobiaceae. Bosea sp. WAO was isolated from pulverized pyritic shale containing elevated levels of arsenic. This aerobic, gram negative microorganism is capable of facultative chemolithoautotrophic growth under aerobic conditions by oxidizing the electron donors arsenite, elemental sulfur, thiosulfate, polysulfide, and amorphous sulfur. The draft genome is of a single circular chromosome 6,125,776 bp long consisting of 21 scaffolds with a G + C content of 66.84%. A total 5727 genes were predicted of which 5665 or 98.92% are protein-coding genes and 62 RNA genes. We identified the genes aioA and aioB, which encode the large and small subunits of the arsenic oxidase respectively. We also identified the genes for the complete sulfur oxidation pathway sox which is used to oxidize thiosulfate to sulfate.}, } @article {pmid29681430, year = {2018}, author = {Russell, CJ and Hu, M and Okda, FA}, title = {Influenza Hemagglutinin Protein Stability, Activation, and Pandemic Risk.}, journal = {Trends in microbiology}, volume = {26}, number = {10}, pages = {841-853}, pmid = {29681430}, issn = {1878-4380}, support = {HHSN272201400006C/AI/NIAID NIH HHS/United States ; }, abstract = {For decades, hemagglutinin (HA) protein structure and its refolding mechanism have served as a paradigm for understanding protein-mediated membrane fusion. HA trimers are in a high-energy state and are functionally activated by low pH. Over the past decade, HA stability (or the pH at which irreversible conformational changes are triggered) has emerged as an important determinant in influenza virus host range, infectivity, transmissibility, and human pandemic potential. Here, we review HA protein structure, assays to measure its stability, measured HA stability values, residues and mutations that regulate its stability, the effect of HA stability on interspecies adaptation and transmissibility, and mechanistic insights into this process. Most importantly, HA stabilization appears to be necessary for adapting emerging influenza viruses to humans.}, } @article {pmid29680748, year = {2018}, author = {Signor, SA and Nuzhdin, SV}, title = {The Evolution of Gene Expression in cis and trans.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {7}, pages = {532-544}, pmid = {29680748}, issn = {0168-9525}, support = {R01 MH091561/MH/NIMH NIH HHS/United States ; U01 GM103804/GM/NIGMS NIH HHS/United States ; }, abstract = {There is abundant variation in gene expression between individuals, populations, and species. The evolution of gene regulation and expression within and between species is thought to frequently contribute to adaptation. Yet considerable evidence suggests that the primary evolutionary force acting on variation in gene expression is stabilizing selection. We review here the results of recent studies characterizing the evolution of gene expression occurring in cis (via linked polymorphisms) or in trans (through diffusible products of other genes) and their contribution to adaptation and response to the environment. We review the evidence for buffering of variation in gene expression at the level of both transcription and translation, and the possible mechanisms for this buffering. Lastly, we summarize unresolved questions about the evolution of gene regulation.}, } @article {pmid29680507, year = {2018}, author = {Torres, C and Barrios, ME and Cammarata, RV and Victoria, M and Fernandez-Cassi, X and Bofill-Mas, S and Colina, R and Blanco Fernández, MD and Mbayed, VA}, title = {Phylodynamics of Merkel-cell polyomavirus and human polyomavirus 6: A long-term history with humans.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {210-220}, doi = {10.1016/j.ympev.2018.04.025}, pmid = {29680507}, issn = {1095-9513}, mesh = {Base Sequence ; Bayes Theorem ; DNA, Viral/genetics ; Humans ; Merkel cell polyomavirus/*classification/genetics/isolation & purification ; *Phylogeny ; Sequence Analysis, DNA ; Time Factors ; }, abstract = {New human polyomaviruses have been described in the last years, including the Merkel-cell polyomavirus (MCPyV; Human polyomavirus 5) and the Human polyomavirus 6 (HPyV6). Although their infection is usually asymptomatic, in immunocompromised host can cause life-threatening pathologies, such as the Merkel cell carcinoma, an aggressive skin neoplasia associated to the MCPyV. Despite being prevalent viruses in population, epidemiological data from South America are scarce, as well as the characterization of the viral types circulating and their origin. The aims of this work were to describe MCPyV and HPyV6 from environmental samples with different geographical origin and to analyze their phylogenetic and evolutionary histories, particularly for MCPyV. Partial and complete genome sequences were obtained from sewage samples from Argentina, Uruguay and Spain. A total number of 87 sequences were obtained for MCPyV and 33 for HPyV6. Phylogenetic analysis showed that MCPyV sequences distributed according to their geographic origin in Europe/North America, Africa, Asia, South America and Oceania groups, suggesting that viral diversification might have followed human migrations across the globe. In particular, viruses from Argentina associated with Europe/North America and South America genotypes, whereas those from Uruguay and Spain also grouped with Africa genotype, reflecting the origin of the current population in each country, which could arrive not only during ancient human migration but also during recent migratory events. In addition, the South American group presented a high level of clusterization, showing internal clusters that could be related to specific locations, such as French Guiana and Brazil or the Southern region into South America, such as Argentina and Uruguay, suggesting a long term evolutionary process in the region. Additionally, in this work, we carried out the first analysis about the evolutionary history of MCPyV trough the integration of phylogenetic, epidemiological and historical data. Since a strong association is observed between the phylogenetic relationships and the origin of the sampled population, this analysis was based on the hypothesis of co-divergence between the virus and human populations. This analysis resulted in a substitution rate of 5.1 × 10-8 s/s/y (∼5.1% of divergence per million years) for the complete genome of MCPyV, which is in the range of those estimated for other double-stranded DNA viruses. Regarding HPyV6, a South American group with clusterization was observed (sequences from Uruguay). Meanwhile, sequences from Argentina grouped with European ones (France and Spain) and remained separated from those isolated in China, USA or Australia. The analysis of viruses from the environment allowed us to deep characterize prevalent infections in different geographic regions, reveling that viruses circulating in each population reflected its origin and that there are specific lineages associated with South America.}, } @article {pmid29680361, year = {2018}, author = {Wang, L and Su, S and Bi, Y and Wong, G and Gao, GF}, title = {Bat-Origin Coronaviruses Expand Their Host Range to Pigs.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {466-470}, doi = {10.1016/j.tim.2018.03.001}, pmid = {29680361}, issn = {1878-4380}, abstract = {Infections with bat-origin coronaviruses have caused severe illness in humans by 'host jump'. Recently, novel bat-origin coronaviruses were found in pigs. The large number of mutations on the receptor-binding domain allowed the viruses to infect the new host, posing a potential threat to both agriculture and public health.}, } @article {pmid29679715, year = {2018}, author = {Fernandes, NM and Vizzoni, VF and Borges, BDN and Soares, CAG and da Silva-Neto, ID and Paiva, TDS}, title = {Molecular phylogeny and comparative morphology indicate that odontostomatids (Alveolata, Ciliophora) form a distinct class-level taxon related to Armophorea.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {382-389}, doi = {10.1016/j.ympev.2018.04.026}, pmid = {29679715}, issn = {1095-9513}, mesh = {Ciliophora/*classification/*genetics/ultrastructure ; DNA, Ribosomal/genetics ; Likelihood Functions ; *Phylogeny ; }, abstract = {The odontostomatids are among the least studied ciliates, possibly due to their small sizes, restriction to anaerobic environments and difficulty in culturing. Consequently, their phylogenetic affinities to other ciliate taxa are still poorly understood. In the present study, we analyzed newly obtained ribosomal gene sequences of the odontostomatids Discomorphella pedroeneasi and Saprodinium dentatum, together with sequences from the literature, including Epalxella antiquorum and a large assemblage of ciliate sequences representing the major recognized classes. The results show that D. pedroeneasi and S. dentatum form a deep-diverging branch related to metopid and clevelandellid armophoreans, corroborating the old literature. However E. antiquorum clustered with the morphologically discrepant plagiopylids, indicating that either the complex odontostomatid body architecture evolved convergently, or the positioning of E. antiquorum as a plagiopylid is artifactual. A new ciliate class, Odontostomatea n. cl., is proposed based on molecular analyses and comparative morphology of odontostomatids with related taxa.}, } @article {pmid29679714, year = {2018}, author = {Zhao, P and Zhou, HJ and Potter, D and Hu, YH and Feng, XJ and Dang, M and Feng, L and Zulfiqar, S and Liu, WZ and Zhao, GF and Woeste, K}, title = {Population genetics, phylogenomics and hybrid speciation of Juglans in China determined from whole chloroplast genomes, transcriptomes, and genotyping-by-sequencing (GBS).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {250-265}, doi = {10.1016/j.ympev.2018.04.014}, pmid = {29679714}, issn = {1095-9513}, mesh = {China ; *Genetic Speciation ; Genetics, Population ; *Genome, Chloroplast ; *Genomics ; Genotyping Techniques ; Geography ; Haplotypes/genetics ; *Hybridization, Genetic ; Juglans/*genetics ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; *Sequence Analysis, DNA ; Transcriptome/*genetics ; }, abstract = {Genomic data are a powerful tool for elucidating the processes involved in the evolution and divergence of species. The speciation and phylogenetic relationships among Chinese Juglans remain unclear. Here, we used results from phylogenomic and population genetic analyses, transcriptomics, Genotyping-By-Sequencing (GBS), and whole chloroplast genomes (Cp genome) data to infer processes of lineage formation among the five native Chinese species of the walnut genus (Juglans, Juglandaceae), a widespread, economically important group. We found that the processes of isolation generated diversity during glaciations, but that the recent range expansion of J. regia, probably from multiple refugia, led to hybrid formation both within and between sections of the genus. In southern China, human dispersal of J. regia brought it into contact with J. sigillata, which we determined to be an ecotype of J. regia that is now maintained as a landrace. In northern China, walnut hybridized with a distinct lineage of J. mandshurica to form J. hopeiensis, a controversial taxon (considered threatened) that our data indicate is a horticultural variety. Comparisons among whole chloroplast genomes and nuclear transcriptome analyses provided conflicting evidence for the timing of the divergence of Chinese Juglans taxa. J. cathayensis and J. mandshurica are poorly differentiated based our genomic data. Reconstruction of Juglans evolutionary history indicate that episodes of climatic variation over the past 4.5 to 33.80 million years, associated with glacial advances and retreats and population isolation, have shaped Chinese walnut demography and evolution, even in the presence of gene flow and introgression.}, } @article {pmid29679713, year = {2018}, author = {Larridon, I and Bauters, K and Semmouri, I and Viljoen, JA and Prychid, CJ and Muasya, AM and Bruhl, JJ and Wilson, KL and Senterre, B and Goetghebeur, P}, title = {Molecular phylogenetics of the genus Costularia (Schoeneae, Cyperaceae) reveals multiple distinct evolutionary lineages.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {196-209}, doi = {10.1016/j.ympev.2018.04.016}, pmid = {29679713}, issn = {1095-9513}, mesh = {Africa ; Bayes Theorem ; Biodiversity ; Cyperaceae/anatomy & histology/*classification/*genetics ; Likelihood Functions ; Madagascar ; New Caledonia ; *Phylogeny ; Sequence Analysis, DNA ; Seychelles ; Time Factors ; }, abstract = {We investigated the monophyly of Costularia (25 species), a genus of tribe Schoeneae (Cyperaceae) that illustrates a remarkable distribution pattern from southeastern Africa, over Madagascar, the Mascarenes and Seychelles, to Malesia and New Caledonia. A further species, Tetraria borneensis, has been suggested to belong to Costularia. Relationships and divergence times were inferred using an existing four marker phylogeny of Cyperaceae tribe Schoeneae expanded with newly generated sequence data mainly for Costularia s.l. species. Phylogenetic reconstruction was executed using Bayesian inference and maximum likelihood approaches. Divergence times were estimated using a relaxed molecular clock model, calibrated with fossil data. Based on our results, Tetraria borneensis is not related to the species of Costularia. Costularia s.l. is composed of four distinct evolutionary lineages. Two lineages, one including the type species, are part of the Oreobolus clade, i.e. a much reduced genus Costularia restricted to southeastern Africa, Madagascar, the Mascarenes and Seychelles, and a small endemic genus from New Caledonia for which a new genus Chamaedendron is erected based on Costularia subgenus Chamaedendron. The other two lineages are part of the Tricostularia clade, i.e. a separate single-species lineage from the Seychelles for which a new genus (Xyroschoenus) is described, and Costularia subgenus Lophoschoenus. For the latter, more research is needed to test whether they are congeneric with the species placed in the reticulate-sheathed Tetraria clade.}, } @article {pmid29679561, year = {2018}, author = {Johnson, PW and Doe, CQ and Lai, SL}, title = {Drosophila nucleostemin 3 is required to maintain larval neuroblast proliferation.}, journal = {Developmental biology}, volume = {440}, number = {1}, pages = {1-12}, pmid = {29679561}, issn = {1095-564X}, support = {R25 HD070817/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle/physiology ; Cell Cycle Proteins/metabolism ; Cell Differentiation/physiology ; Cell Division/physiology ; Cell Polarity/physiology ; Cell Proliferation/physiology ; Drosophila Proteins/*genetics/*metabolism/physiology ; Drosophila melanogaster/embryology/genetics/metabolism ; GTP-Binding Proteins/*genetics/*metabolism/physiology ; Larva/metabolism ; Neural Stem Cells/*metabolism/physiology ; Neurogenesis ; Neurons/metabolism ; }, abstract = {Stem cells must maintain proliferation during tissue development, repair and homeostasis, yet avoid tumor formation. In Drosophila, neural stem cells (neuroblasts) maintain proliferation during embryonic and larval development and terminate cell cycle during metamorphosis. An important question for understanding how tissues are generated and maintained is: what regulates stem cell proliferation versus differentiation? We performed a genetic screen which identified nucleostemin 3 (ns3) as a gene required to maintain neuroblast proliferation. ns3 is evolutionarily conserved with yeast and human Lsg1, which encode putative GTPases and are essential for organism growth and viability. We found NS3 is cytoplasmic and it is required to retain the cell cycle repressor Prospero in neuroblast cytoplasm via a Ran-independent pathway. NS3 is also required for proper neuroblast cell polarity and asymmetric cell division. Structure-function analysis further shows that the GTP-binding domain and acidic domain are required for NS3 function in neuroblast proliferation. We conclude NS3 has novel roles in regulating neuroblast cell polarity and proliferation.}, } @article {pmid29679560, year = {2018}, author = {Sefton, EM and Gallardo, M and Kardon, G}, title = {Developmental origin and morphogenesis of the diaphragm, an essential mammalian muscle.}, journal = {Developmental biology}, volume = {440}, number = {2}, pages = {64-73}, pmid = {29679560}, issn = {1095-564X}, support = {F32 HD093425/HD/NICHD NIH HHS/United States ; P41 GM103545/GM/NIGMS NIH HHS/United States ; R01 EB023947/EB/NIBIB NIH HHS/United States ; R01 HD087360/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Connective Tissue/embryology/physiology ; Diaphragm/*embryology/*physiology ; Disease Models, Animal ; Gene Expression Regulation, Developmental/genetics ; Genes, Developmental/genetics ; Mammals ; Mice ; Mice, Inbred C57BL ; Morphogenesis ; Muscle Development/physiology ; Muscle, Skeletal/embryology/growth & development/physiology ; }, abstract = {The diaphragm is a mammalian skeletal muscle essential for respiration and for separating the thoracic and abdominal cavities. Development of the diaphragm requires the coordinated development of muscle, muscle connective tissue, tendon, nerves, and vasculature that derive from different embryonic sources. However, defects in diaphragm development are common and the cause of an often deadly birth defect, Congenital Diaphragmatic Hernia (CDH). Here we comprehensively describe the normal developmental origin and complex spatial-temporal relationship between the different developing tissues to form a functional diaphragm using a developmental series of mouse embryos genetically and immunofluorescently labeled and analyzed in whole mount. We find that the earliest developmental events are the emigration of muscle progenitors from cervical somites followed by the projection of phrenic nerve axons from the cervical neural tube. Muscle progenitors and phrenic nerve target the pleuroperitoneal folds (PPFs), transient pyramidal-shaped structures that form between the thoracic and abdominal cavities. Subsequently, the PPFs expand across the surface of the liver to give rise to the muscle connective tissue and central tendon, and the leading edge of their expansion precedes muscle morphogenesis, formation of the vascular network, and outgrowth and branching of the phrenic nerve. Thus development and morphogenesis of the PPFs is critical for diaphragm formation. In addition, our data indicate that the earliest events in diaphragm development are critical for the etiology of CDH and instrumental to the evolution of the diaphragm. CDH initiates prior to E12.5 in mouse and suggests that defects in the early PPF formation or their ability to recruit muscle are an important source of CDH. Also, the recruitment of muscle progenitors from cervical somites to the nascent PPFs is uniquely mammalian and a key developmental innovation essential for the evolution of the muscularized diaphragm.}, } @article {pmid29679559, year = {2018}, author = {Newman, EA and Kim, DW and Wan, J and Wang, J and Qian, J and Blackshaw, S}, title = {Foxd1 is required for terminal differentiation of anterior hypothalamic neuronal subtypes.}, journal = {Developmental biology}, volume = {439}, number = {2}, pages = {102-111}, pmid = {29679559}, issn = {1095-564X}, support = {R01 DK108230/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anterior Hypothalamic Nucleus/metabolism/physiology ; Body Patterning/genetics ; Cell Differentiation/genetics ; Eye Proteins/genetics/metabolism ; Forkhead Transcription Factors/*genetics/*metabolism/physiology ; Gene Expression Regulation, Developmental/genetics ; Homeodomain Proteins/genetics/metabolism ; Hypothalamus/metabolism ; Mice ; Nerve Tissue Proteins/genetics/metabolism ; Neurogenesis/physiology ; Neurons/metabolism ; Neuropeptides/genetics/metabolism ; Stem Cells/metabolism/physiology ; Transcription Factors/metabolism ; }, abstract = {Although the hypothalamus functions as a master homeostat for many behaviors, little is known about the transcriptional networks that control its development. To investigate this question, we analyzed mice deficient for the Forkhead domain transcription factor Foxd1. Foxd1 is selectively expressed in neuroepithelial cells of the prethalamus and hypothalamus prior to the onset of neurogenesis, and is later restricted to neural progenitors of the prethalamus and anterior hypothalamus. During early stages of neurogenesis, we observed that Foxd1-deficient mice showed reduced expression of Six3 and Vax1 in anterior hypothalamus, but overall patterning of the prethalamus and hypothalamus is unaffected. After neurogenesis is complete, however, a progressive reduction and eventual loss of expression of molecular markers of the suprachiasmatic, paraventricular and periventricular hypothalamic is observed. These findings demonstrate that Foxd1 acts in hypothalamic progenitors to allow sustained expression of a subset of genes selectively expressed in mature neurons of the anterior hypothalamus.}, } @article {pmid29679558, year = {2018}, author = {Xu, R and Li, J and Zhao, H and Kong, R and Wei, M and Shi, L and Bai, G and Li, Z}, title = {Self-restrained regulation of stem cell niche activity by niche components in the Drosophila testis.}, journal = {Developmental biology}, volume = {439}, number = {1}, pages = {42-51}, doi = {10.1016/j.ydbio.2018.04.011}, pmid = {29679558}, issn = {1095-564X}, support = {R01 GM084947/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/physiology ; Drosophila/embryology/genetics ; Drosophila Proteins/genetics/*metabolism/physiology ; Gene Expression Regulation, Developmental/genetics ; Germ Cells/cytology ; Male ; Protein-Serine-Threonine Kinases/*metabolism/physiology ; Receptors, Cell Surface/*metabolism/physiology ; Signal Transduction/physiology ; Stem Cell Niche/*genetics/*physiology ; Stem Cells/cytology ; Testis/metabolism/physiology ; }, abstract = {Most, if not all, stem cells reside in a defined microenvironment, called the niche. Short-ranged niche signal must be tightly controlled to be active only inside the niche to maintain the proper balance of stem cell self-renewal verse differentiation. However, how niche components restrict localized niche signal activation remains largely unknown. Here, we find that Thickveins (Tkv, a type I receptor of the Dpp signaling pathway) in cyst stem cells (CySCs) of the testis niche prevents Dpp signaling activation outside of the niche. We show that Tkv functions as Dpp trap/sink to spatially restrain Dpp signaling inside the niche. This self-restrained regulation of niche activity by Tkv in CySCs is independent of the canonical Dpp signaling pathway. Our data demonstrate the critical roles of niche components (CySCs) in the self-restrained regulation of niche activity, which could be shed light on niche activity regulation in general.}, } @article {pmid29679501, year = {2018}, author = {Rodrigues, AMM and Taylor, TB}, title = {Ecological and demographic correlates of cooperation from individual to budding dispersal.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {1058-1070}, doi = {10.1111/jeb.13286}, pmid = {29679501}, issn = {1420-9101}, abstract = {Identifying the ecological and demographic factors that promote the evolution of cooperation is a major challenge for evolutionary biologists. Explanations for the adaptive evolution of cooperation seek to determine which factors make reproduction in cooperative groups more favourable than independent breeding or other selfish strategies. A vast majority of the hypotheses posit that cooperative groups emerge in the context of philopatry, high costs of dispersal, high population density and environmental stability. This route to cooperation, however, fails to explain a growing body of empirical evidence in which cooperation is not associated with one or more of these predictors. We propose an alternative evolutionary path towards the emergence of cooperation that accounts for the disparities observed in the current literature. We find that when dispersal is mediated by a group mode of dispersal, commonly termed budding dispersal, our mathematical model reveals an association between cooperation and immigration, lower costs of dispersal, low population density and environmental variability. Furthermore, by studying the continuum from the individual to the partial and full budding mode of dispersal, we can explicitly explain why the correlates of cooperation change under budding. This enables us to outline a general model for the evolution of cooperation that accounts for a substantial amount of empirical evidence. Our results suggest that natural selection may have favoured two major contrasting pathways for the evolution of cooperation depending on a set of key ecological and demographic factors.}, } @article {pmid29679205, year = {2018}, author = {Lyu, G and Tan, T and Guan, Y and Sun, L and Liang, Q and Tao, W}, title = {Changes in the position and volume of inactive X chromosomes during the G0/G1 transition.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {3}, pages = {179-189}, pmid = {29679205}, issn = {1573-6849}, support = {91219101//National Natural Science Foundation of China/International ; 31471205//National Natural Science Foundation of China/International ; 31571394//National Natural Science Foundation of China/International ; No. 2013CB530700//National Basic Research Program of China/International ; 0223-0002-0002000-56//Hunan Province Cooperative Innovation Center for Molecular Target New Drug Study/International ; }, mesh = {Animals ; Cell Line ; Chromosomes, Mammalian/*metabolism ; Female ; G1 Phase/*physiology ; Mice ; Resting Phase, Cell Cycle/*physiology ; X Chromosome/*metabolism ; X Chromosome Inactivation/*physiology ; }, abstract = {In female mammals, each cell silences one X chromosome by converting it into transcriptionally inert heterochromatin. The inactivation is concomitant with epigenetic changes including methylation of specific histone residues and incorporation of macroH2A. Such epigenetic changes may exert influence on the positioning of the inactive X chromosome (Xi) within the nucleus beyond the level of chromatin structure. However, the dynamic positioning of the inactive X chromosome during cell cycle remains unclear. Here, we show that H3K27me3 is a cell-cycle-independent marker for the inactivated X chromosomes in WI38 cells. By utilizing this marker, three types of Xi locations in the nuclei are classified, which are envelope position (associated with envelope), mid-position (between the envelope and nucleolus), and nucleolus position (associated with the nucleolus). Moreover, serial-section analysis revealed that the inactive X chromosomes in the mid-position appear to be sparser and less condensed than those associated with the nuclear envelope or nucleolus. During the transition from G0 to G1 phase, the inactive X chromosomes tend to move from the envelope position to the nucleolus position in WI38 cells. Our results imply a role of chromosome positioning in maintaining the organization of the inactive X chromosomes in different cell phases.}, } @article {pmid29679096, year = {2018}, author = {Kurahashi, R and Sano, S and Takano, K}, title = {Protein Evolution is Potentially Governed by Protein Stability: Directed Evolution of an Esterase from the Hyperthermophilic Archaeon Sulfolobus tokodaii.}, journal = {Journal of molecular evolution}, volume = {86}, number = {5}, pages = {283-292}, pmid = {29679096}, issn = {1432-1432}, support = {25440194//Japan Society for the Promotion of Science/ ; 17K07368//Japan Society for the Promotion of Science/ ; }, abstract = {The study of evolution is important to understand biological phenomena. During evolutionary processes, genetic changes confer amino acid substitutions in proteins, resulting in new or improved functions. Unfortunately, most mutations destabilize proteins. Thus, protein stability is a significant factor in evolution; however, its role remains unclear. Here, we simply and directly explored the association between protein activity and stability in random mutant libraries to elucidate the role of protein stability in evolutionary processes. In the first random mutation of an esterase from Sulfolobus tokodaii, approximately 20% of the variants displayed higher activity than wild-type protein (i.e., 20% evolvability). During evolutionary processes, the evolvability depended on the stability of template proteins, indicating that protein evolution is potentially governed by protein stability. Furthermore, decreased activity could be recovered during evolution by maintaining the stability of variants. The results suggest that protein sequence space for its evolution is able to expand during nearly neutral evolution where mutations are slightly deleterious for activity but rarely fatal for stability. Molecular evolution is a crucial phenomenon that has continued since the birth of life on earth, and mechanism underlying it is simple; therefore, this could be demonstrated by our simple experiments. These findings also can be applied to protein engineering.}, } @article {pmid29679064, year = {2018}, author = {Zhang, H and Li, Y and Wang, HB and Zhang, A and Chen, ML and Fang, ZX and Dong, XD and Li, SB and Du, Y and Xiong, D and He, JY and Li, MZ and Liu, YM and Zhou, AJ and Zhong, Q and Zeng, YX and Kieff, E and Zhang, Z and Gewurz, BE and Zhao, B and Zeng, MS}, title = {Author Correction: Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry.}, journal = {Nature microbiology}, volume = {3}, number = {9}, pages = {1075}, doi = {10.1038/s41564-018-0155-1}, pmid = {29679064}, issn = {2058-5276}, abstract = {In the version of this Letter originally published, the authors reported on the use of 2,5-dimethylpyrrolyl benzoic acid to block Ephrin receptors. In 2011, it was reported that newly synthesized 2,5-dimethylpyrrolyl benzoic acid lacked the previously reported EphA2 antagonizing activity1. However, the purchased compound did in fact have the activity initially reported, suggesting that an uncharacterized alteration occurred during storage. The authors therefore wish to clarify that the compound used in their study should be more accurately referred to as a 2,5-dimethylpyrrolyl benzoic acid derivative. All references to 2,5-dimethylpyrrolyl benzoic acid in the Letter have now been changed to reflect this.Although 2,5-dimethylpyrrolyl benzoic acid derivatives have been reported to have off-target effects2, as do most small-molecule inhibitors, the multiple complementary methods and techniques used demonstrate that EphA2 is a key Epstein-Barr virus epithelial cell receptor. The conclusions of the study are therefore unchanged.}, } @article {pmid29679044, year = {2018}, author = {}, title = {Path to protection.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {753}, doi = {10.1038/s41559-018-0555-x}, pmid = {29679044}, issn = {2397-334X}, } @article {pmid29679035, year = {2018}, author = {Rowe, S and Rose, GA}, title = {Canadian cod comeback derailed.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {436}, doi = {10.1038/d41586-018-04898-4}, pmid = {29679035}, issn = {1476-4687}, mesh = {Animals ; Canada ; *Fisheries ; *Gadus morhua ; }, } @article {pmid29678829, year = {2018}, author = {Wei, C and Yang, H and Wang, S and Zhao, J and Liu, C and Gao, L and Xia, E and Lu, Y and Tai, Y and She, G and Sun, J and Cao, H and Tong, W and Gao, Q and Li, Y and Deng, W and Jiang, X and Wang, W and Chen, Q and Zhang, S and Li, H and Wu, J and Wang, P and Li, P and Shi, C and Zheng, F and Jian, J and Huang, B and Shan, D and Shi, M and Fang, C and Yue, Y and Li, F and Li, D and Wei, S and Han, B and Jiang, C and Yin, Y and Xia, T and Zhang, Z and Bennetzen, JL and Zhao, S and Wan, X}, title = {Draft genome sequence of Camellia sinensis var. sinensis provides insights into the evolution of the tea genome and tea quality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4151-E4158}, pmid = {29678829}, issn = {1091-6490}, mesh = {Camellia sinensis/*genetics/metabolism ; *Evolution, Molecular ; *Gene Duplication ; *Genome, Plant ; *Tea ; }, abstract = {Tea, one of the world's most important beverage crops, provides numerous secondary metabolites that account for its rich taste and health benefits. Here we present a high-quality sequence of the genome of tea, Camellia sinensis var. sinensis (CSS), using both Illumina and PacBio sequencing technologies. At least 64% of the 3.1-Gb genome assembly consists of repetitive sequences, and the rest yields 33,932 high-confidence predictions of encoded proteins. Divergence between two major lineages, CSS and Camellia sinensis var. assamica (CSA), is calculated to ∼0.38 to 1.54 million years ago (Mya). Analysis of genic collinearity reveals that the tea genome is the product of two rounds of whole-genome duplications (WGDs) that occurred ∼30 to 40 and ∼90 to 100 Mya. We provide evidence that these WGD events, and subsequent paralogous duplications, had major impacts on the copy numbers of secondary metabolite genes, particularly genes critical to producing three key quality compounds: catechins, theanine, and caffeine. Analyses of transcriptome and phytochemistry data show that amplification and transcriptional divergence of genes encoding a large acyltransferase family and leucoanthocyanidin reductases are associated with the characteristic young leaf accumulation of monomeric galloylated catechins in tea, while functional divergence of a single member of the glutamine synthetase gene family yielded theanine synthetase. This genome sequence will facilitate understanding of tea genome evolution and tea metabolite pathways, and will promote germplasm utilization for breeding improved tea varieties.}, } @article {pmid29678646, year = {2018}, author = {Cao, YN and Wang, IJ and Chen, LY and Ding, YQ and Liu, LX and Qiu, YX}, title = {Inferring spatial patterns and drivers of population divergence of Neolitsea sericea (Lauraceae), based on molecular phylogeography and landscape genomics.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {162-172}, doi = {10.1016/j.ympev.2018.04.010}, pmid = {29678646}, issn = {1095-9513}, mesh = {Bayes Theorem ; Climate ; DNA, Chloroplast/genetics ; DNA, Ribosomal Spacer/genetics ; Genetic Loci ; Genetics, Population ; *Genomics ; Lauraceae/*genetics ; Likelihood Functions ; Models, Genetic ; Phylogeny ; *Phylogeography ; Polymorphism, Single Nucleotide/genetics ; Probability ; Sequence Analysis, DNA ; }, abstract = {The relative roles of geography, climate and ecology in driving population divergence and (incipient) speciation has so far been largely neglected in studies addressing the evolution of East Asia's island flora. Here, we employed chloroplast and ribosomal DNA sequences and restriction site-associated DNA sequencing (RADseq) loci to investigate the phylogeography and drivers of population divergence of Neolitsea sericea. These data sets support the subdivision of N. sericea populations into the Southern and Northern lineages across the 'Tokara gap'. Two distinct sublineages were further identified for the Northern lineage of N. sericea from the RADseq data. RADseq was also used along with approximate Bayesian computation to show that the current distribution and differentiation of N. sericea populations resulted from a combination of relatively ancient migration and successive vicariant events that likely occurred during the mid to late Pleistocene. Landscape genomic analyses showed that, apart from geographic barriers, barrier, potentially local adaptation to different climatic conditions appears to be one of the major drivers for lineage diversification of N. sericea.}, } @article {pmid29678645, year = {2018}, author = {Guo, X and Thomas, DC and Saunders, RMK}, title = {Gene tree discordance and coalescent methods support ancient intergeneric hybridisation between Dasymaschalon and Friesodielsia (Annonaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {14-29}, doi = {10.1016/j.ympev.2018.04.009}, pmid = {29678645}, issn = {1095-9513}, abstract = {Although hybridisation between closely related species is common and known to be important in plant evolution, hybridisation at the generic level or above is comparatively rare. We address ancient intergeneric hybridisation in the early-divergent angiosperm family Annonaceae by phylogenetic reconstruction, divergence time estimation and coalescent simulation of the genus Dasymaschalon using a multi-locus approach based on molecular data from five chloroplast (matK, psbA-trnH, ndhF, rbcL, and trnL-F) and five nuclear (ITS, ETS, AP3, PhyA, and PhyC) DNA markers. We demonstrate incongruence among different gene trees: Dasymaschalon is retrieved as monophyletic in the nuclear ribosomal tree (based on ITS and ETS), but is non-monophyletic in the chloroplast and Phy-gene trees (with poor resolution in the AP3 tree), with the majority of species assigned to a strongly supported clade but three species (D. filipes, D. longiflorum and D. tibetense) more closely related to the sister genus Friesodielsia. Three contrasting approaches-a coalescent method based on molecular dating, incongruence pattern comparison, and a multi-accession phylogenetic reconstruction-are used to assess the patterns of this gene tree incongruence and test hypotheses of ancient hybridisation and incomplete lineage sorting. Our results support a late Miocene intergeneric hybridisation between members of the Dasymaschalon and Friesodielsia lineages in continental Asia-west Malesia.}, } @article {pmid29678644, year = {2018}, author = {Beasley-Hall, PG and Tierney, SM and Weinstein, P and Austin, AD}, title = {A revised phylogeny of macropathine cave crickets (Orthoptera: Rhaphidophoridae) uncovers a paraphyletic Australian fauna.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {153-161}, doi = {10.1016/j.ympev.2018.04.024}, pmid = {29678644}, issn = {1095-9513}, mesh = {Animals ; Australia ; Bayes Theorem ; *Caves ; Genetic Variation ; Gryllidae/*classification/genetics ; New Zealand ; *Phylogeny ; Time Factors ; }, abstract = {Australian cave crickets are members of the subfamily Macropathinae (Orthoptera: Rhaphidophoridae). The subfamily is thought to have originated prior to the tectonic separation of the supercontinent Gondwana based on distributions of extant lineages and molecular phylogenetic evidence, although the Australian fauna have been underrepresented in previous studies. The current study augments existing multigene data (using 12S, 16S, and 28S rRNA genes) to investigate the placement of the Australian representatives within the Macropathinae and to assess divergence dates of select clades. Results suggest that the endemic Tasmanian genus Parvotettix is the sister lineage to the remaining members of the subfamily, an outcome that presents a paraphyletic Australian fauna in contrast to previous studies. All other Australian taxa represented in this study (Micropathus and Novotettix) emerged as a sister group to the New Zealand and South American macropathine lineages. Estimation of phylogenetic divergence ages among the aforementioned clades were calibrated using two methods, in absence of suitable fossil records: (i) tectonic events depicting the fragmentation of Gondwanan landmasses that invoke vicariant scenarios of present day geographic distributions; and (ii) molecular evolutionary rates. Geological calibrations place the median age of the most recent common ancestor of extant macropathines at ∼125 to ∼165 Ma, whereas analyses derived from molecular substitution rates suggest a considerably younger origin of ∼32 Ma. This phylogenetic study represents the most rigorous taxonomic sampling of the Australian cave cricket fauna to date and stresses the influence of lineage representation on biogeographic inference.}, } @article {pmid29678445, year = {2018}, author = {Vermillion, KL and Bacher, R and Tannenbaum, AP and Swanson, S and Jiang, P and Chu, LF and Stewart, R and Thomson, JA and Vereide, DT}, title = {Spatial patterns of gene expression are unveiled in the chick primitive streak by ordering single-cell transcriptomes.}, journal = {Developmental biology}, volume = {439}, number = {1}, pages = {30-41}, doi = {10.1016/j.ydbio.2018.04.007}, pmid = {29678445}, issn = {1095-564X}, mesh = {Animals ; Chick Embryo ; Chickens ; Gastrulation/*genetics ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental/genetics ; Primitive Streak/*embryology/physiology ; Single-Cell Analysis/*methods ; Spatio-Temporal Analysis ; Transcriptome/genetics ; }, abstract = {During vertebrate development, progenitor cells give rise to tissues and organs through a complex choreography that commences at gastrulation. A hallmark event of gastrulation is the formation of the primitive streak, a linear assembly of cells along the anterior-posterior (AP) axis of the developing organism. To examine the primitive streak at a single-cell resolution, we measured the transcriptomes of individual chick cells from the streak or the surrounding tissue (the rest of the area pellucida) in Hamburger-Hamilton stage 4 embryos. The single-cell transcriptomes were then ordered by the statistical method Wave-Crest to deduce both the relative position along the AP axis and the prospective lineage of single cells. The ordered transcriptomes reveal intricate patterns of gene expression along the primitive streak.}, } @article {pmid29678198, year = {2018}, author = {Hoyles, L and Jiménez-Pranteda, ML and Chilloux, J and Brial, F and Myridakis, A and Aranias, T and Magnan, C and Gibson, GR and Sanderson, JD and Nicholson, JK and Gauguier, D and McCartney, AL and Dumas, ME}, title = {Metabolic retroconversion of trimethylamine N-oxide and the gut microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {73}, pmid = {29678198}, issn = {2049-2618}, support = {MR/L01632X/1//Medical Research Council/United Kingdom ; }, mesh = {Adult ; Animals ; Bacteria ; Chromatography, High Pressure Liquid ; Female ; Fermentation ; *Gastrointestinal Microbiome ; Humans ; In Situ Hybridization, Fluorescence ; Magnetic Resonance Spectroscopy ; Male ; *Metabolome ; *Metabolomics/methods ; Methylamines/blood/*metabolism ; Mice ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: The dietary methylamines choline, carnitine, and phosphatidylcholine are used by the gut microbiota to produce a range of metabolites, including trimethylamine (TMA). However, little is known about the use of trimethylamine N-oxide (TMAO) by this consortium of microbes.

RESULTS: A feeding study using deuterated TMAO in C57BL6/J mice demonstrated microbial conversion of TMAO to TMA, with uptake of TMA into the bloodstream and its conversion to TMAO. Microbial activity necessary to convert TMAO to TMA was suppressed in antibiotic-treated mice, with deuterated TMAO being taken up directly into the bloodstream. In batch-culture fermentation systems inoculated with human faeces, growth of Enterobacteriaceae was stimulated in the presence of TMAO. Human-derived faecal and caecal bacteria (n = 66 isolates) were screened on solid and liquid media for their ability to use TMAO, with metabolites in spent media analysed by 1H-NMR. As with the in vitro fermentation experiments, TMAO stimulated the growth of Enterobacteriaceae; these bacteria produced most TMA from TMAO. Caecal/small intestinal isolates of Escherichia coli produced more TMA from TMAO than their faecal counterparts. Lactic acid bacteria produced increased amounts of lactate when grown in the presence of TMAO but did not produce large amounts of TMA. Clostridia (sensu stricto), bifidobacteria, and coriobacteria were significantly correlated with TMA production in the mixed fermentation system but did not produce notable quantities of TMA from TMAO in pure culture.

CONCLUSIONS: Reduction of TMAO by the gut microbiota (predominantly Enterobacteriaceae) to TMA followed by host uptake of TMA into the bloodstream from the intestine and its conversion back to TMAO by host hepatic enzymes is an example of metabolic retroconversion. TMAO influences microbial metabolism depending on isolation source and taxon of gut bacterium. Correlation of metabolomic and abundance data from mixed microbiota fermentation systems did not give a true picture of which members of the gut microbiota were responsible for converting TMAO to TMA; only by supplementing the study with pure culture work and additional metabolomics was it possible to increase our understanding of TMAO bioconversions by the human gut microbiota.}, } @article {pmid29678163, year = {2018}, author = {Pereira, MB and Wallroth, M and Jonsson, V and Kristiansson, E}, title = {Comparison of normalization methods for the analysis of metagenomic gene abundance data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {274}, pmid = {29678163}, issn = {1471-2164}, mesh = {*Data Analysis ; *Metagenomics ; }, abstract = {BACKGROUND: In shotgun metagenomics, microbial communities are studied through direct sequencing of DNA without any prior cultivation. By comparing gene abundances estimated from the generated sequencing reads, functional differences between the communities can be identified. However, gene abundance data is affected by high levels of systematic variability, which can greatly reduce the statistical power and introduce false positives. Normalization, which is the process where systematic variability is identified and removed, is therefore a vital part of the data analysis. A wide range of normalization methods for high-dimensional count data has been proposed but their performance on the analysis of shotgun metagenomic data has not been evaluated.

RESULTS: Here, we present a systematic evaluation of nine normalization methods for gene abundance data. The methods were evaluated through resampling of three comprehensive datasets, creating a realistic setting that preserved the unique characteristics of metagenomic data. Performance was measured in terms of the methods ability to identify differentially abundant genes (DAGs), correctly calculate unbiased p-values and control the false discovery rate (FDR). Our results showed that the choice of normalization method has a large impact on the end results. When the DAGs were asymmetrically present between the experimental conditions, many normalization methods had a reduced true positive rate (TPR) and a high false positive rate (FPR). The methods trimmed mean of M-values (TMM) and relative log expression (RLE) had the overall highest performance and are therefore recommended for the analysis of gene abundance data. For larger sample sizes, CSS also showed satisfactory performance.

CONCLUSIONS: This study emphasizes the importance of selecting a suitable normalization methods in the analysis of data from shotgun metagenomics. Our results also demonstrate that improper methods may result in unacceptably high levels of false positives, which in turn may lead to incorrect or obfuscated biological interpretation.}, } @article {pmid29678154, year = {2018}, author = {Uga, Y and Assaranurak, I and Kitomi, Y and Larson, BG and Craft, EJ and Shaff, JE and McCouch, SR and Kochian, LV}, title = {Genomic regions responsible for seminal and crown root lengths identified by 2D & 3D root system image analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {273}, pmid = {29678154}, issn = {1471-2164}, mesh = {Genome, Plant/genetics ; *Genomics ; *Imaging, Three-Dimensional ; Oryza/*genetics ; Phenotype ; Plant Roots/*genetics ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: Genetic improvement of root system architecture is a promising approach for improved uptake of water and mineral nutrients distributed unevenly in the soil. To identify genomic regions associated with the length of different root types in rice, we quantified root system architecture in a set of 26 chromosome segment substitution lines derived from a cross between lowland indica rice, IR64, and upland tropical japonica rice, Kinandang Patong, (IK-CSSLs), using 2D & 3D root phenotyping platforms.

RESULTS: Lengths of seminal and crown roots in the IK-CSSLs grown under hydroponic conditions were measured by 2D image analysis (RootReader2D). Twelve CSSLs showed significantly longer seminal root length than the recurrent parent IR64. Of these, 8 CSSLs also exhibited longer total length of the three longest crown roots compared to IR64. Three-dimensional image analysis (RootReader3D) for these CSSLs grown in gellan gum revealed that only one CSSL, SL1003, showed significantly longer total root length than IR64. To characterize the root morphology of SL1003 under soil conditions, SL1003 was grown in Turface, a soil-like growth media, and roots were quantified using RootReader3D. SL1003 had larger total root length and increased total crown root length than did IR64, although its seminal root length was similar to that of IR64. The larger TRL in SL1003 may be due to increased crown root length.

CONCLUSIONS: SL1003 carries an introgression from Kinandang Patong on the long arm of chromosome 1 in the genetic background of IR64. We conclude that this region harbors a QTL controlling crown root elongation.}, } @article {pmid29678151, year = {2018}, author = {Izuogu, OG and Alhasan, AA and Mellough, C and Collin, J and Gallon, R and Hyslop, J and Mastrorosa, FK and Ehrmann, I and Lako, M and Elliott, DJ and Santibanez-Koref, M and Jackson, MS}, title = {Analysis of human ES cell differentiation establishes that the dominant isoforms of the lncRNAs RMST and FIRRE are circular.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {276}, pmid = {29678151}, issn = {1471-2164}, support = {RPG-2012-795//Leverhulme Trust/ ; Fellowship No. 614620//European Research Council/International ; BBJ014516/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/K018957/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 614620//European Research Council/International ; //Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Cell Differentiation/*genetics ; Down-Regulation ; Exons/genetics ; Genetic Loci/genetics ; Human Embryonic Stem Cells/*cytology ; Humans ; Neurons/cytology ; RNA Isoforms/*genetics ; RNA, Long Noncoding/*genetics ; Sequence Analysis, RNA ; Time Factors ; Transcription, Genetic ; }, abstract = {BACKGROUND: Circular RNAs (circRNAs) are predominantly derived from protein coding genes, and some can act as microRNA sponges or transcriptional regulators. Changes in circRNA levels have been identified during human development which may be functionally important, but lineage-specific analyses are currently lacking. To address this, we performed RNAseq analysis of human embryonic stem (ES) cells differentiated for 90 days towards 3D laminated retina.

RESULTS: A transcriptome-wide increase in circRNA expression, size, and exon count was observed, with circRNA levels reaching a plateau by day 45. Parallel statistical analyses, controlling for sample and locus specific effects, identified 239 circRNAs with expression changes distinct from the transcriptome-wide pattern, but these all also increased in abundance over time. Surprisingly, circRNAs derived from long non-coding RNAs (lncRNAs) were found to account for a significantly larger proportion of transcripts from their loci of origin than circRNAs from coding genes. The most abundant, circRMST:E12-E6, showed a > 100X increase during differentiation accompanied by an isoform switch, and accounts for > 99% of RMST transcripts in many adult tissues. The second most abundant, circFIRRE:E10-E5, accounts for > 98% of FIRRE transcripts in differentiating human ES cells, and is one of 39 FIRRE circRNAs, many of which include multiple unannotated exons.

CONCLUSIONS: Our results suggest that during human ES cell differentiation, changes in circRNA levels are primarily globally controlled. They also suggest that RMST and FIRRE, genes with established roles in neurogenesis and topological organisation of chromosomal domains respectively, are processed as circular lncRNAs with only minor linear species.}, } @article {pmid29678149, year = {2018}, author = {Kim, JI and Yoon, HS and Yi, G and Shin, W and Archibald, JM}, title = {Comparative mitochondrial genomics of cryptophyte algae: gene shuffling and dynamic mobile genetic elements.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {275}, pmid = {29678149}, issn = {1471-2164}, support = {NRF-2013R1A1A3012539, 2015R1D1A1A01057899//National Research Foundation of Korea/ ; 2017R1A2B3001923//National Research Foundation of Korea/ ; 2016R1D1A1A09919318//National Research Foundation of Korea/ ; 2015R1A2A2A01003192, 2015M1A5A1041808//National Research Foundation of Korea/ ; the Collaborative Genome Program (20140428)//Ministry of Oceans and Fisheries/ ; Dongguk University Research Fund of 2016//Dongguk University/ ; an operating grant from the Natural Sciences and Engineering Research Council of Canada//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Cryptophyta/*genetics ; Gene Rearrangement ; Genome, Mitochondrial/*genetics ; *Genomics ; Interspersed Repetitive Sequences/*genetics ; Phylogeny ; }, abstract = {BACKGROUND: Cryptophytes are an ecologically important group of algae comprised of phototrophic, heterotrophic and osmotrophic species. This lineage is of great interest to evolutionary biologists because their plastids are of red algal secondary endosymbiotic origin. Cryptophytes have a clear phylogenetic affinity to heterotrophic eukaryotes and possess four genomes: host-derived nuclear and mitochondrial genomes, and plastid and nucleomorph genomes of endosymbiotic origin.

RESULTS: To gain insight into cryptophyte mitochondrial genome evolution, we sequenced the mitochondrial DNAs of five species and performed a comparative analysis of seven genomes from the following cryptophyte genera: Chroomonas, Cryptomonas, Hemiselmis, Proteomonas, Rhodomonas, Storeatula and Teleaulax. The mitochondrial genomes were similar in terms of their general architecture, gene content and presence of a large repeat region. However, gene order was poorly conserved. Characteristic features of cryptophyte mtDNAs included large syntenic clusters resembling α-proteobacterial operons that encode bacteria-like rRNAs, tRNAs, and ribosomal protein genes. The cryptophyte mitochondrial genomes retain almost all genes found in many other eukaryotes including the nad, sdh, cox, cob, and atp genes, with the exception of sdh2 and atp3. In addition, gene cluster analysis showed that cryptophytes possess a gene order closely resembling the jakobid flagellates Jakoba and Reclinomonas. Interestingly, the cox1 gene of R. salina, T. amphioxeia, and Storeatula species was found to contain group II introns encoding a reverse transcriptase protein, as did the cob gene of Storeatula species CCMP1868.

CONCLUSIONS: These newly sequenced genomes increase the breadth of data available from algae and will aid in the identification of general trends in mitochondrial genome evolution. While most of the genomes were highly conserved, extensive gene arrangements have shuffled gene order, perhaps due to genome rearrangements associated with hairpin-containing mobile genetic elements, tRNAs with palindromic sequences, and tandem repeat sequences. The cox1 and cob gene sequences suggest that introns have recently been acquired during cryptophyte evolution. Comparison of phylogenetic trees based on plastid and mitochondrial genome data sets underscore the different evolutionary histories of the host and endosymbiont components of present-day cryptophytes.}, } @article {pmid29678141, year = {2018}, author = {Beltrán-López, RG and Domínguez-Domínguez, O and Pérez-Rodríguez, R and Piller, K and Doadrio, I}, title = {Evolving in the highlands: the case of the Neotropical Lerma live-bearing Poeciliopsis infans (Woolman, 1894) (Cyprinodontiformes: Poeciliidae) in Central Mexico.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {56}, pmid = {29678141}, issn = {1471-2148}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Climate ; Cyprinodontiformes/genetics/*physiology ; Cytochromes b/genetics ; DNA, Mitochondrial/genetics ; *Ecosystem ; Fresh Water ; Genes, Mitochondrial ; Genetic Variation ; Genetics, Population ; Geography ; Haplotypes/genetics ; Mexico ; Mitochondria/genetics ; Phylogeny ; Species Specificity ; Time Factors ; *Tropical Climate ; }, abstract = {BACKGROUND: Volcanic and tectonic activities in conjunction with Quaternary climate are the main events that shaped the geographical distribution of genetic variation of many lineages. Poeciliopsis infans is the only poeciliid species that was able to colonize the temperate highlands of central Mexico. We inferred the phylogenetic relationships, biogeographic history, and historical demography in the widespread Neotropical species P. infans and correlated this with geological events and the Quaternary glacial-interglacial climate in the highlands of central Mexico, using the mitochondrial genes Cytochrome b and Cytochrome oxidase I and two nuclear loci, Rhodopsin and ribosomal protein S7.

RESULTS: Populations of P. infans were recovered in two well-differentiated clades. The maximum genetic distances between the two clades were 3.3% for cytb, and 1.9% for coxI. The divergence of the two clades occurred ca. 2.83 Myr. Ancestral area reconstruction revealed a complex biogeographical history for P. infans. The Bayesian Skyline Plot showed a demographic decline, although more visible for clade A, and more recently showed a population expansion in the last 0.025 Myr. Finally, the habitat suitability modelling showed that during the LIG, clade B had more areas with high probabilities of presence in comparison to clade A, whereas for the LGM, clade A showed more areas with high probabilities of presence in comparisons to clade B.

CONCLUSIONS: Poeciliopsis infans has had a complex evolutionary and biogeographic history, which, as in other co-distributed freshwater fishes, seems to be linked to the volcanic and tectonic activities during the Pliocene or early Pleistocene. Populations of P. infans distributed in lowlands showed a higher level of genetic diversity than populations distributed in highlands, which could be linked to more stable and higher temperatures in lowland areas. The fluctuations in population size through time are in agreement with the continuous fluctuations of the climate of central Mexico.}, } @article {pmid29678140, year = {2018}, author = {Gibbin, E and Gavish, A and Domart-Coulon, I and Kramarsky-Winter, E and Shapiro, O and Meibom, A and Vardi, A}, title = {Using NanoSIMS coupled with microfluidics to visualize the early stages of coral infection by Vibrio coralliilyticus.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {39}, pmid = {29678140}, issn = {1471-2180}, abstract = {BACKGROUND: Global warming has triggered an increase in the prevalence and severity of coral disease, yet little is known about coral/pathogen interactions in the early stages of infection. The point of entry of the pathogen and the route that they take once inside the polyp is currently unknown, as is the coral's capacity to respond to infection. To address these questions, we developed a novel method that combines stable isotope labelling and microfluidics with transmission electron microscopy (TEM) and nanoscale secondary ion mass spectrometry (NanoSIMS), to monitor the infection process between Pocillopora damicornis and Vibrio coralliilyticus under elevated temperature.

RESULTS: Three coral fragments were inoculated with 15N-labeled V. coralliilyticus and then fixed at 2.5, 6 and 22 h post-inoculation (hpi) according to the virulence of the infection. Correlative TEM/NanoSIMS imaging was subsequently used to visualize the penetration and dispersal of V. coralliilyticus and their degradation or secretion products. Most of the V. coralliilyticus cells we observed were located in the oral epidermis of the fragment that experienced the most virulent infection (2.5 hpi). In some cases, these bacteria were enclosed within electron dense host-derived intracellular vesicles. 15N-enriched pathogen-derived breakdown products were visible in all tissue layers of the coral polyp (oral epidermis, oral gastrodermis, aboral gastrodermis), at all time points, although the relative 15N-enrichment depended on the time at which the corals were fixed. Tissues in the mesentery filaments had the highest density of 15N-enriched hotspots, suggesting these tissues act as a "collection and digestion" site for pathogenic bacteria. Closer examination of the sub-cellular structures associated with these 15N-hotspots revealed these to be host phagosomal and secretory cells/vesicles.

CONCLUSIONS: This study provides a novel method for tracking bacterial infection dynamics at the levels of the tissue and single cell and takes the first steps towards understanding the complexities of infection at the microscale, which is a crucial step towards understanding how corals will fare under global warming.}, } @article {pmid29678131, year = {2018}, author = {Kirpich, AS and Ibarra, M and Moskalenko, O and Fear, JM and Gerken, J and Mi, X and Ashrafi, A and Morse, AM and McIntyre, LM}, title = {SECIMTools: a suite of metabolomics data analysis tools.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {151}, pmid = {29678131}, issn = {1471-2105}, support = {Genetics Institute//University of Florida/International ; U24 DK097209/NH/NIH HHS/United States ; U24 DK097209/DK/NIDDK NIH HHS/United States ; HiPerGator//University of Florida/International ; II Fellowship//University of Florida/International ; }, mesh = {Analysis of Variance ; Cluster Analysis ; Discriminant Analysis ; Humans ; Least-Squares Analysis ; Metabolomics/*methods ; Principal Component Analysis ; Quality Control ; Reproducibility of Results ; *Software ; *Statistics as Topic ; Support Vector Machine ; Workflow ; }, abstract = {BACKGROUND: Metabolomics has the promise to transform the area of personalized medicine with the rapid development of high throughput technology for untargeted analysis of metabolites. Open access, easy to use, analytic tools that are broadly accessible to the biological community need to be developed. While technology used in metabolomics varies, most metabolomics studies have a set of features identified. Galaxy is an open access platform that enables scientists at all levels to interact with big data. Galaxy promotes reproducibility by saving histories and enabling the sharing workflows among scientists.

RESULTS: SECIMTools (SouthEast Center for Integrated Metabolomics) is a set of Python applications that are available both as standalone tools and wrapped for use in Galaxy. The suite includes a comprehensive set of quality control metrics (retention time window evaluation and various peak evaluation tools), visualization techniques (hierarchical cluster heatmap, principal component analysis, modular modularity clustering), basic statistical analysis methods (partial least squares - discriminant analysis, analysis of variance, t-test, Kruskal-Wallis non-parametric test), advanced classification methods (random forest, support vector machines), and advanced variable selection tools (least absolute shrinkage and selection operator LASSO and Elastic Net).

CONCLUSIONS: SECIMTools leverages the Galaxy platform and enables integrated workflows for metabolomics data analysis made from building blocks designed for easy use and interpretability. Standard data formats and a set of utilities allow arbitrary linkages between tools to encourage novel workflow designs. The Galaxy framework enables future data integration for metabolomics studies with other omics data.}, } @article {pmid29678129, year = {2018}, author = {Ozer, EA}, title = {ClustAGE: a tool for clustering and distribution analysis of bacterial accessory genomic elements.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {150}, pmid = {29678129}, issn = {1471-2105}, support = {U19 AI135964/AI/NIAID NIH HHS/United States ; MRSG-13-220-01 - MPC//American Cancer Society/International ; }, mesh = {Algorithms ; Base Sequence ; Cluster Analysis ; Genes, Bacterial ; *Genome, Bacterial ; Genomic Islands/genetics ; Phylogeny ; Pseudomonas aeruginosa/*genetics/isolation & purification ; *Software ; }, abstract = {BACKGROUND: The non-conserved accessory genome of bacteria can be associated with important adaptive characteristics that can contribute to niche specificity or pathogenicity of strains. High degrees of structural and compositional diversity in genomic islands and other elements of the accessory genome can complicate characterization of accessory genome contents among populations of strains. Methods for easily and effectively defining the distributions of discrete elements of the accessory genome among bacterial strains in a population are needed to explore the relationships between the flexible genome and bacterial adaptive traits.

RESULTS: We have developed the open-source software package ClustAGE. This program, written in Perl, uses BLAST to cluster nucleotide accessory genomic elements from the genomes of multiple bacterial strains and to identify their distribution within the study population. The program output can be used in combination with strain phenotype data or other characteristics to detect associations. Optional graphical output is available for visualizing accessory genome gene content and distribution patterns. The capabilities of the software are demonstrated on a collection of 14 Pseudomonas aeruginosa genome sequences.

CONCLUSIONS: The ClustAGE software and utilities are effective for identifying characteristics and distributions of accessory genomic elements among groups of bacterial genomes. The ability to easily and effectively characterize the accessory genome of a sequence collection may provide a better understanding of the accessory genome's contribution to a species' adaptation and pathogenesis. The ClustAGE source code can be downloaded from https://clustage.sourceforge.io and a limited web-based implementation is available at http://vfsmspineagent.fsm.northwestern.edu/cgi-bin/clustage.cgi .}, } @article {pmid29678128, year = {2018}, author = {Anekthanakul, K and Hongsthong, A and Senachak, J and Ruengjitchatchawalya, M}, title = {SpirPep: an in silico digestion-based platform to assist bioactive peptides discovery from a genome-wide database.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {149}, pmid = {29678128}, issn = {1471-2105}, support = {P-11-01089//Bioinformatics and Systems Biology HRD project, National Center for Genetic Engineering and Biotechnology (BIOTEC), NSTDA, Thailand/International ; 58000492//National Research University Project, King Mongkut's University of Technology Thonburi/International ; }, mesh = {Amino Acid Sequence ; Animals ; Computational Biology/*methods ; *Computer Simulation ; *Databases, Protein ; *Genome ; Humans ; Peptides/*analysis ; *Software ; Workflow ; }, abstract = {BACKGROUND: Bioactive peptides, including biological sources-derived peptides with different biological activities, are protein fragments that influence the functions or conditions of organisms, in particular humans and animals. Conventional methods of identifying bioactive peptides are time-consuming and costly. To quicken the processes, several bioinformatics tools are recently used to facilitate screening of the potential peptides prior their activity assessment in vitro and/or in vivo. In this study, we developed an efficient computational method, SpirPep, which offers many advantages over the currently available tools.

RESULTS: The SpirPep web application tool is a one-stop analysis and visualization facility to assist bioactive peptide discovery. The tool is equipped with 15 customized enzymes and 1-3 miscleavage options, which allows in silico digestion of protein sequences encoded by protein-coding genes from single, multiple, or genome-wide scaling, and then directly classifies the peptides by bioactivity using an in-house database that contains bioactive peptides collected from 13 public databases. With this tool, the resulting peptides are categorized by each selected enzyme, and shown in a tabular format where the peptide sequences can be tracked back to their original proteins. The developed tool and webpages are coded in PHP and HTML with CSS/JavaScript. Moreover, the tool allows protein-peptide alignment visualization by Generic Genome Browser (GBrowse) to display the region and details of the proteins and peptides within each parameter, while considering digestion design for the desirable bioactivity. SpirPep is efficient; it takes less than 20 min to digest 3000 proteins (751,860 amino acids) with 15 enzymes and three miscleavages for each enzyme, and only a few seconds for single enzyme digestion. Obviously, the tool identified more bioactive peptides than that of the benchmarked tool; an example of validated pentapeptide (FLPIL) from LC-MS/MS was demonstrated. The web and database server are available at http://spirpepapp.sbi.kmutt.ac.th .

CONCLUSION: SpirPep, a web-based bioactive peptide discovery application, is an in silico-based tool with an overview of the results. The platform is a one-stop analysis and visualization facility; and offers advantages over the currently available tools. This tool may be useful for further bioactivity analysis and the quantitative discovery of desirable peptides.}, } @article {pmid29676786, year = {2018}, author = {Verin, M and Tellier, A}, title = {Host-parasite coevolution can promote the evolution of seed banking as a bet-hedging strategy.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13483}, pmid = {29676786}, issn = {1558-5646}, abstract = {Seed (egg) banking is a common bet-hedging strategy maximizing the fitness of organisms facing environmental unpredictability by the delayed emergence of offspring. Yet, this condition often requires fast and drastic stochastic shifts between good and bad years. We hypothesize that the host seed banking strategy can evolve in response to coevolution with parasites because the coevolutionary cycles promote a gradually changing environment over longer times than seed persistence. We study the evolution of host germination fraction as a quantitative trait using both pairwise competition and multiple mutant competition methods, while the germination locus can be genetically linked or unlinked with the host locus under coevolution. In a gene-for-gene model of coevolution, hosts evolve a seed bank strategy under unstable coevolutionary cycles promoted by moderate to high costs of resistance or strong disease severity. Moreover, when assuming genetic linkage between coevolving and germination loci, the resistant genotype always evolves seed banking in contrast to susceptible hosts. Under a matching-allele interaction, both hosts' genotypes exhibit the same seed banking strategy irrespective of the genetic linkage between loci. We suggest host-parasite coevolution as an additional hypothesis for the evolution of seed banking as a temporal bet-hedging strategy.}, } @article {pmid29676775, year = {2018}, author = {Lasne, C and Hangartner, SB and Connallon, T and Sgrò, CM}, title = {Cross-sex genetic correlations and the evolution of sex-specific local adaptation: Insights from classical trait clines in Drosophila melanogaster.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1317-1327}, doi = {10.1111/evo.13494}, pmid = {29676775}, issn = {1558-5646}, abstract = {Natural selection varies widely among locations of a species' range, favoring population divergence and adaptation to local environmental conditions. Selection also differs between females and males, favoring the evolution of sexual dimorphism. Both forms of within-species evolutionary diversification are widely studied, though largely in isolation, and it remains unclear whether environmental variability typically generates similar or distinct patterns of selection on each sex. Studies of sex-specific local adaptation are also challenging because they must account for genetic correlations between female and male traits, which may lead to correlated patterns of trait divergence between sexes, whether or not local selection patterns are aligned or differ between the sexes. We quantified sex-specific divergence in five clinally variable traits in Drosophila melanogaster that individually vary in their magnitude of cross-sex genetic correlation (i.e., from moderate to strongly positive). In all five traits, we observed parallel male and female clines, regardless of the magnitude of their genetic correlation. These patterns imply that parallel spatial divergence of female and male traits is a reflection of sexually concordant directional selection imposed by local environmental conditions. In such contexts, genetic correlations between the sexes promote, rather than constrain, local adaptation to a spatially variable environment.}, } @article {pmid29676774, year = {2018}, author = {Aguilar-Rodríguez, J and Peel, L and Stella, M and Wagner, A and Payne, JL}, title = {The architecture of an empirical genotype-phenotype map.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1242-1260}, pmid = {29676774}, issn = {1558-5646}, abstract = {Recent advances in high-throughput technologies are bringing the study of empirical genotype-phenotype (GP) maps to the fore. Here, we use data from protein-binding microarrays to study an empirical GP map of transcription factor (TF) -binding preferences. In this map, each genotype is a DNA sequence. The phenotype of this DNA sequence is its ability to bind one or more TFs. We study this GP map using genotype networks, in which nodes represent genotypes with the same phenotype, and edges connect nodes if their genotypes differ by a single small mutation. We describe the structure and arrangement of genotype networks within the space of all possible binding sites for 525 TFs from three eukaryotic species encompassing three kingdoms of life (animal, plant, and fungi). We thus provide a high-resolution depiction of the architecture of an empirical GP map. Among a number of findings, we show that these genotype networks are "small-world" and assortative, and that they ubiquitously overlap and interface with one another. We also use polymorphism data from Arabidopsis thaliana to show how genotype network structure influences the evolution of TF-binding sites in vivo. We discuss our findings in the context of regulatory evolution.}, } @article {pmid29676730, year = {2018}, author = {Zhang, J and Guo, C and Chen, W and de Lajudie, P and Zhang, Z and Shang, Y and Wang, ET}, title = {Mesorhizobium wenxiniae sp. nov., isolated from chickpea (Cicer arietinum L.) in China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1930-1936}, doi = {10.1099/ijsem.0.002770}, pmid = {29676730}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Cicer/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Mesorhizobium/*classification/genetics/isolation & purification ; Multilocus Sequence Typing ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Symbiosis ; }, abstract = {Three chickpea rhizobial strains (WYCCWR 10195T=S1-3-7, WYCCWR 10198=S1-4-3 and WYCCWR 10200=S1-5-1) isolated from Northwest China formed a group affiliated to Mesorhizobium based on 16S rRNA gene sequence comparison. To clarify their species status, multilocus sequence analysis and average nucleotide identity (ANI) values of whole genome sequences between the novel group and the type strains of the related species were further performed. Similarities of 95.7-96.6 % in the concatenated sequences of atpD-recA-glnII and 91.9-93.1 % of ANI values to the closest-related species Mesorhizobium muleiense, Mesorhizobium mediterraneum and Mesorhizobium temperatum demonstrated the novel group a unique genospecies. The most abundant fatty acid in cells of WYCCWR 10195T were C19 : 0 cyclo ω8c (51.4 %), followed by C18 : 1 ω7c 11-methyl (9.5 %) and C16 : 0 (9.3 %). Its genome size was 6.37 Mbp, comprising 6633 predicted genes with a DNA G+C content of 61.9 mol%. The similarities of 99.0-99.8 % for the nodC gene and 98.3-99.44 % for the nifH gene to those of the chickpea rhizobial species and nodulation with Cicer arietinum L. confirmed the strains of the new genospecies as symbiovar ciceri. The weak utilization of most of the tested sugars/organic acids and non-utilization of l(+)-rhamnose, l-cysteine and l-glycine as sole carbon source, tolerance to 1 % (w/v) NaCl, resistance to 5 µg ml-1 chloromycetin and non-hydrolysis of l-tyrosine distinguished the novel group from the related species and supported this group as a novel species, for which the name Mesorhizobium wenxiniae sp. nov. is proposed, with WYCCWR 10195T (=S1-3-7=HAMBI 3692T=LMG 30254T) as the type strain.}, } @article {pmid29676729, year = {2018}, author = {Into, P and Pontes, A and Jacques, N and Casaregola, S and Limtong, S and Sampaio, JP}, title = {Papiliotrema plantarum sp. nov., a novel tremellaceous sexual yeast species.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1937-1941}, doi = {10.1099/ijsem.0.002771}, pmid = {29676729}, issn = {1466-5034}, mesh = {Basidiomycota/*classification/genetics/isolation & purification ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; French Guiana ; Mycological Typing Techniques ; *Phylogeny ; Plant Leaves/*microbiology ; RNA, Ribosomal/genetics ; Sequence Analysis, DNA ; Spores, Fungal ; Zea mays/*microbiology ; }, abstract = {During a survey of the yeast community associated with the phylloplane of corn in Thailand, a basidiomycetous yeast strain belonging to the genus Papiliotrema was isolated. Analyses of the D1/D2 domains of the 26S (LSU) rRNA gene and complete ITS region supported the recognition of a novel species, for which the name Papiliotrema plantarum sp. nov. is proposed (type strain DMKU-CP801T=CBS 15220T=PYCC 7257T). Another strain of P. plantarum sp. nov., isolated in French Guiana, was found to be sexually compatible with the Thai isolate and mycelium with clamp connections, basidia and basidiospores were observed in culture. The basidial morphology of P. plantarum combined features previously observed for Papiliotrema bandonii and Papiliotrema fuscus, which represent the only sexual species hitherto known in the genus, i.e. transversely septate basidia, with sexual structures of the Tremella type.}, } @article {pmid29676726, year = {2018}, author = {Han, SB and Yu, YH and Ju, Z and Li, Y and Zhang, R and Hou, XJ and Ma, XY and Yu, XY and Sun, C and Wu, M}, title = {Rhodohalobacter barkolensis sp. nov., isolated from a saline lake and emended description of the genus Rhodohalobacter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1949-1954}, doi = {10.1099/ijsem.0.002775}, pmid = {29676726}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Gram-Negative Aerobic Rods and Cocci/*classification/genetics/isolation & purification ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-negative, non-motile, aerobic, rod-shaped bacterium, designated 15182T, was isolated from a saline lake in China. The novel strain 15182T was able to grow at 10-40 °C (optimum, 37 °C), pH 7.0-8.0 (optimum, 7.5) and with 0.5-4 % NaCl (optimum, 2-3 %, w/v). The phylogenetic analysis based on 16S rRNA gene sequences revealed that strain 15182T was most closely related to the genus Rhodohalobacter by sharing the highest sequence similarity of 97.0 % with Rhodohalobacter halophilus JZ3C29T. Chemotaxonomic analysis showed that the sole respiratory quinone was menaquinone 7, the major fatty acids included C16 : 0 N alcohol and C16 : 1ω11c. The major polar lipids included diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four uncharacterized glycolipids, one uncharacterized phospholipid and two uncharacterized lipids. The genomic DNA G+C content of the strain 15182T was 42.4 mol%. The average nucleotide identity value between 15182T and R. halophilus JZ3C29T was 75.4 %, and the in silico DNA-DNA hybridization value of the two strains was 19.1 %. On the basis of its phenotypic, chemotaxonomic, genotypic and genomic characteristics presented in this study, strain 15182T is suggested to represent a novel species in the genus Rhodohalobacter, for which the name Rhodohalobacter barkolensis sp. nov. is proposed. The type strain is 15182T (=KCTC 62172T=MCCC 1K03442T). An emended description of the genus Rhodohalobacter is also presented.}, } @article {pmid29676723, year = {2018}, author = {Gao, ZH and Zhong, SF and Lu, ZE and Xiao, SY and Qiu, LH}, title = {Paraburkholderia caseinilytica sp. nov., isolated from the pine and broad-leaf mixed forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1963-1968}, doi = {10.1099/ijsem.0.002774}, pmid = {29676723}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Burkholderiaceae/*classification/genetics/isolation & purification ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative, aerobic, non-spore-forming, motile and rod-shaped bacterial strain, designated HM451T, was isolated from forest soil sampled at the Dinghushan Biosphere Reserve, Guangdong Province, PR China (112° 31' E 23° 10' N). It grew optimally at 28 °C, pH 5.0-6.0 and in the presence of 0-2.5 % (w/v) NaCl on R2A medium. Strain HM451T was closely related to Paraburkholderia mimosarum NBRC 106338T (98.6 % 16S rRNA gene sequence similarity), Paraburkholderia heleia NBRC 101817T (98.4 %) and Paraburkholderia silvatlantica SRMrh-20T (98.0 %). The 16S rRNA gene sequence analysis showed that strain HM451T and the three closely related strains formed a clade within the genus Paraburkholderia, but was clearly separated from the established species. The DNA-DNA relatedness value between strain HM451T and its phylogenetically closest relative, P. mimosarum NBRC 106338T, was much lower than 70 %. Strain HM451T contained ubiquinone 8 as the major respiratory quinone. Major fatty acids were C16 : 0, C17 : 0cyclo and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The DNA G+C content of strain HM451T was 65.4 mol%. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, two unidentified aminophospholipids, one unidentified aminolipid and a polar lipid. The phenotypic, chemotaxonomic and phylogenetic data showed that strain HM451T represents a novel species of the genus Paraburkholderia, for which the name Paraburkholderia caseinilytica sp. nov. is proposed. The type strain is HM451T (=GDMCC 1.1190T=LMG 30092T).}, } @article {pmid29676722, year = {2018}, author = {Lee, Y and Jeon, CO}, title = {Siphonobacter curvatus sp. nov., isolated from a freshwater river.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1925-1929}, doi = {10.1099/ijsem.0.002769}, pmid = {29676722}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rivers/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel orange-pigmented, Gram-stain-negative and strictly aerobic bacterium, designated strain HR-UT, was isolated from a water sample of the Han River located in the Republic of Korea. Cells were catalase-positive and oxidase-positive, and non-motile curved rods without flagella. The strain grew at 5-35 °C (optimum 25 °C), pH 6-10 (optimum of 7-8) and 0-3 % (w/v) NaCl (optimum 0 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HR-UT formed a tight phylogenic lineage with Siphonobacter aquaeclarae DSM 21668T and 'Siphonobacter intestinalis' 63MJ-2. The 16S rRNA gene sequence comparison of strain HR-UT and other reported type strains showed that it shared the highest sequence similarity to S. aquaeclarae DSM 21668T (96.9 %) and 'S. intestinalis' 63MJ-2 (96.6 %), and had lower similarities than 87.0 % to other bacteria with validly published names. Average nucleotide identity and in silico DNA-DNA hybridization values between strain HR-UT and the most closely related strain S. aquaeclarae were 71.7 and 18.4 %, respectively. The major respiratory quinone was menaquinone-7, and the dominant fatty acids (>5 %) consisted of C16 : 1ω5c, summed feature 3 (comprising C16 : 1ω7c and/or iso-C15 : 0 2-OH) and iso-C15 : 0. The polar lipids comprised phosphatidylethanolamine, four unidentified aminolipids and three unidentified lipids. The DNA G+C content was 47.9 mol%. Based on the genotypic, chemotaxonomic and phenotypic analyses, strain HR-UT represents a novel species of the genus Siphonobacter, for which the name Siphonobacter curvatus sp. nov. is proposed. The type strain is HR-UT (=KACC 19409T=JCM 32267T).}, } @article {pmid29676721, year = {2018}, author = {Lee, Y and Jeon, CO}, title = {Flavobacterium alvei sp. nov., isolated from a freshwater river.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1919-1924}, doi = {10.1099/ijsem.0.002768}, pmid = {29676721}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rivers/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A yellow-pigmented, Gram-stain-negative, strictly aerobic, catalase-negative and oxidase-positive bacterium, designated strain HR-AYT, was isolated from a water sample of the Han River. Cells were non-motile rods without flagella. Growth was observed at 5-30 °C (optimum, 20 °C), pH 5-9 (optimum, pH 7) and 0 % NaCl. The major respiratory quinone was menaquinone-6. Strain HR-AYT did not produce flexirubin-type pigments. The major fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), anteiso-C15 : 0, iso-C15 : 0 and C16 : 0. The polar lipids comprised phosphatidylethanolamine and an unidentified phosphoamino lipid as major polar lipids, and four unidentified lipids were also detected as minor lipids. The DNA G+C content of strain HR-AYT was 34.4 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain HR-AYT belonged to the family Flavobacteriaceae in the phylum Bacteroidetes, and formed a phylogenic lineage with members of the genus Flavobacterium. The 16S rRNA gene sequence similarity showed that strain HR-AYT was most closely related to Flavobacterium chungbukense CS100T (97.91 %) and Flavobacterium glaciei 0499T (97.74 %). Based on these results, strain HR-AYT represents a novel species of the genus Flavobacterium, for which the name Flavobacterium alvei sp. nov. is proposed. The type strain is HR-AYT (=KACC 19407T=JCM 32264T).}, } @article {pmid29676719, year = {2018}, author = {Meng, YC and Liu, HC and Zhou, YG and Cai, M and Kang, Y}, title = {Vibrio gangliei sp. nov., a novel member of Vibrionaceae isolated from sawdust in a pigpen.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1969-1974}, doi = {10.1099/ijsem.0.002779}, pmid = {29676719}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Housing, Animal ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Swine ; Vibrio/*classification/genetics/isolation & purification ; }, abstract = {A Gram-stain-negative, rod-shaped, catalase- and oxidase-positive, facultatively anaerobic, and motile bacterium, designated strain SZDIS-1T, was isolated from pigpen sawdust bedding in Xiamen, Fujian Province, China. Cells grew at 10-50 °C, pH 6.0-9.0, up to 12 % (w/v) NaCl, resisted vibriostatic agent O/129 and were negative for gelatin and alginate hydrolysis. No growth on thiosulfate citrate bile salts sucrose agar medium. Based on 16S rRNA gene sequences and multilocus sequence analysis, this strain should be assigned to the genus Vibrio, with the closest relatives being Vibrio aphrogenes CA-1004T (97.7 % 16S rRNA gene sequence pairwise similarity), Vibrio algivorus SA2T (96.6 %), Vibrio casei WS 4539T (96.3 %), Vibrio rumoiensis S-1T (96.1 %) and Vibrio litoralis MANO22DT (95.5 %), but separate from them by large distances in different phylogenetic trees. Based on whole genome analysis, the orthologous average nucleotide identity and in silico DNA-DNA hybridization values against the five relatives were 76.1-78.7 and 20.1-28.7 %. The major fatty acids were summed feature 3 (C16 : 1ω7c/C16 : 1ω6c), C16 : 0, summed feature 2 (one or more of C12 : 0 aldehyde, C14 : 0 3OH and/or iso-C16 : 1) and summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c). The DNA G+C content was 43.0 mol% from whole genomic sequence analysis. Therefore, phylogenetic, genotypic, phenotypic and chemotaxonomic characteristics showed that the isolate represented a novel species of the genus Vibrio, for which the name Vibrio gangliei sp. nov. is proposed. The type strain is SZDIS-1T (=DSM 104291T=CGMCC 1.15236T).}, } @article {pmid29676718, year = {2018}, author = {Zhou, GW and Yang, XR and Wadaan, MAM and Hozzein, WN and Zheng, BX and Su, JQ and Zhu, YG}, title = {Propionicimonas ferrireducens sp. nov., isolated from dissimilatory iron(III)-reducing microbial enrichment obtained from paddy soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1914-1918}, doi = {10.1099/ijsem.0.002766}, pmid = {29676718}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; *Iron ; Nucleic Acid Hybridization ; Oryza ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel strain, designated Y1A-10 4-9-1T, with Gram-stain-positive and rod-shaped cells, was isolated from paddy soil in Yingtan, Jiangxi, China. Cells were 0.15-0.2 µm wide and 1.5-3.3 µm long. The optimal growth temperature was 30 °C and the optimal pH was 7.0. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the novel strain is closely related to Propionicimonas paludicola JCM 11933T (98.57 %). The genomic DNA G+C content was 63.9 mol%. The predominant menaquinone was MK-9(H4) and meso-diaminopimelic acid was present in the cell-wall peptidoglycan layer. The major polar lipids were diphosphatidylglycerol, one unidentified phospholipid and two unidentified lipids. The dominant cellular fatty acids detected were anteiso-C15 : 0 and iso-C16 : 0. The phylogenetic and phenotypic results supported that strain Y1A-10 4-9-1T is a novel species of the genus Propionicimonas, for which the name Propionicimonas ferrireducens sp. nov. is proposed. The type strain is Y1A-10 4-9-1T (=CCTCC AB 2016249T=KCTC 15566T=LMG 29810T).}, } @article {pmid29676514, year = {2018}, author = {Ford, LE and Henderson, KJ and Smiseth, PT}, title = {Differential effects of offspring and maternal inbreeding on egg laying and offspring performance in the burying beetle Nicrophorus vespilloides.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {1047-1057}, doi = {10.1111/jeb.13285}, pmid = {29676514}, issn = {1420-9101}, abstract = {We investigate the effect of offspring and maternal inbreeding on maternal and offspring traits associated with early offspring fitness in the burying beetle Nicrophorus vespilloides. We conducted two experiments. In the first experiment, we manipulated maternal inbreeding only (keeping offspring outbred) by generating mothers that were outbred, moderately inbred or highly inbred. Meanwhile, in the second experiment, we manipulated offspring inbreeding only (keeping females outbred) by generating offspring that were outbred, moderately inbred or highly inbred. In both experiments, we monitored subsequent effects on breeding success (number of larvae), maternal traits (clutch size, delay until laying, laying skew, laying spread and egg size) and offspring traits (hatching success, larval survival, duration of larval development and average larval mass). Maternal inbreeding reduced breeding success, and this effect was mediated through lower hatching success and greater larval mortality. Furthermore, inbred mothers produced clutches where egg laying was less skewed towards the early part of laying than outbred females. This reduction in the skew in egg laying is beneficial for larval survival, suggesting that inbred females adjusted their laying patterns facultatively, thereby partially compensating for the detrimental effects of maternal inbreeding on offspring. Finally, we found evidence of a nonlinear effect of offspring inbreeding coefficient on number of larvae dispersing. Offspring inbreeding affected larval survival and larval development time but also unexpectedly affected maternal traits (clutch size and delay until laying), suggesting that females adjust clutch size and the delay until laying in response to being related to their mate.}, } @article {pmid29676060, year = {2018}, author = {Ghislandi, PG and Pekár, S and Matzke, M and Schulte-Döinghaus, S and Bilde, T and Tuni, C}, title = {Resource availability, mating opportunity and sexual selection intensity influence the expression of male alternative reproductive tactics.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {1035-1046}, doi = {10.1111/jeb.13284}, pmid = {29676060}, issn = {1420-9101}, abstract = {The expression of alternative reproductive tactics can be plastic and occur simultaneously depending on cues that vary spatially or temporally. For example, variation in resources and sexual selection intensity is expected to influence the pay-off of each tactic and shape the decision of which tactic to employ. Males of the nuptial gift-giving spider Pisaura mirabilis can adopt three tactics: offering a genuine prey gift, a 'worthless' non-nutritious gift or no gift. We hypothesized that resources and/or male body condition, and mating opportunity and sexual selection intensity, vary over the course of the mating season to shape the co-existence of alternative traits. We measured these variables in the field over two seasons, to investigate the predictions that as the mating season progresses, (i) males become more likely to employ a gift-giving tactic, and (ii) the likelihood of switching from worthless to genuine gifts increases. Prey availability increased over the season and co-varied with the propensity of males to employ the gift-giving tactic, but we found no support for condition-dependent gift giving. Males responded to an increase in female availability by increasing their mating effort (gift production). Furthermore, the frequency of genuine gift use increased with sexual selection intensity, consistent with the assumption that sperm competition intensity increases with time. Our results suggest that the frequency of alternative tactics is shaped by seasonal changes in ecological factors and sexual selection. This leads to relaxed selection for the gift-giving tactic early in the season when females are less choosy and resources more scarce, and increased selection for genuine gifts later in the season driven by mating opportunity and risk of sperm competition.}, } @article {pmid29675836, year = {2018}, author = {Nagy, LG and Kovács, GM and Krizsán, K}, title = {Complex multicellularity in fungi: evolutionary convergence, single origin, or both?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1778-1794}, doi = {10.1111/brv.12418}, pmid = {29675836}, issn = {1469-185X}, support = {P2014/12//Hungarian Academy of Sciences/International ; ERC_HU Grant #118722//NRDI Office/International ; }, abstract = {Complex multicellularity represents the most advanced level of biological organization and it has evolved only a few times: in metazoans, green plants, brown and red algae and fungi. Compared to other lineages, the evolution of multicellularity in fungi follows different principles; both simple and complex multicellularity evolved via unique mechanisms not found in other lineages. Herein we review ecological, palaeontological, developmental and genomic aspects of complex multicellularity in fungi and discuss general principles of the evolution of complex multicellularity in light of its fungal manifestations. Fungi represent the only lineage in which complex multicellularity shows signatures of convergent evolution: it appears 8-11 times in distinct fungal lineages, which show a patchy phylogenetic distribution yet share some of the genetic mechanisms underlying complex multicellular development. To explain the patchy distribution of complex multicellularity across the fungal phylogeny we identify four key observations: the large number of apparently independent complex multicellular clades; the lack of documented phenotypic homology between these clades; the conservation of gene circuits regulating the onset of complex multicellular development; and the existence of clades in which the evolution of complex multicellularity is coupled with limited gene family diversification. We discuss how these patterns and known genetic aspects of fungal development can be reconciled with the genetic theory of convergent evolution to explain the pervasive occurrence of complex multicellularity across the fungal tree of life.}, } @article {pmid29675544, year = {2018}, author = {Ni, H and Li, N and Qiu, J and Chen, Q and He, J}, title = {Biodegradation of Pendimethalin by Paracoccus sp. P13.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1077-1083}, pmid = {29675544}, issn = {1432-0991}, support = {31760031//the National Natural Science Foundation of China/ ; 31600080//the National Natural Science Foundation of China/ ; 20171BAB214002//the Natural Science Foundation of Jiangxi Province/ ; ZR2016CB29//the Natural Science Foundation of Shandong Province/ ; }, mesh = {Aniline Compounds/*metabolism ; *Biodegradation, Environmental ; Carbon Dioxide/metabolism ; Chromatography, High Pressure Liquid ; Herbicides/*metabolism ; Paracoccus/*growth & development/*metabolism ; RNA, Ribosomal, 16S/genetics ; Soil Microbiology ; Tandem Mass Spectrometry ; Water/metabolism ; }, abstract = {In this study, a bacterial strain P13 capable of degrading pendimethalin was isolated from the soil of a fruit garden. Based on observed cellular morphology and physiology characteristics and a phylogenetic analysis of 16S rRNA gene sequences, strain P13 was identified as a member of the genus Paracoccus. Strain P13 grew on pendimethalin as the sole carbon source, and could degrade 100 mg/L pendimethalin within 2 days and 200 mg/L pendimethalin within 5 days. Pendimethalin degradation was proposed to be initiated by oxidation ring cleavage to yield 1,3-dinitro-2-(pentan-3-ylamino)butane-1,4-diol, an alkane organic compound that was identified by ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS), which then underwent a series of enzymatic reactions to produce CO2 and H2O. The optimal pH and temperature for pendimethalin degradation by strain P13 were 7.0 and 30 °C, respectively. This study identified the bacterial strain Paracoccus sp. P13, which degraded pendimethalin with a relatively high efficiency, and presents a previously unreported microbial pendimethalin degradation pathway.}, } @article {pmid29674747, year = {2018}, author = {Poole, J and Day, CJ and von Itzstein, M and Paton, JC and Jennings, MP}, title = {Glycointeractions in bacterial pathogenesis.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {7}, pages = {440-452}, doi = {10.1038/s41579-018-0007-2}, pmid = {29674747}, issn = {1740-1534}, abstract = {Many important interactions between bacterial pathogens and their hosts are highly specific binding events that involve host or pathogen carbohydrate structures (glycans). Glycan interactions can mediate adhesion, invasion and immune evasion and can act as receptors for toxins. Several bacterial pathogens can also enzymatically alter host glycans to reveal binding targets, degrade the host cell glycans or alter the function of host glycoproteins. In recent years, high-throughput screening technologies, such as lectin, glycan and mucin microarrays, have transformed the field by identifying new bacterial-host glycointeractions, which are crucial for colonization, persistence and disease. In this Review, we discuss interactions involving both host and bacterial glycans that have a role in bacterial pathogenesis. We also highlight recent technological advances that have illuminated the glycoscience of microbial pathogenesis.}, } @article {pmid29674745, year = {2018}, author = {Smith, JJ and Timoshevskaya, N and Ye, C and Holt, C and Keinath, MC and Parker, HJ and Cook, ME and Hess, JE and Narum, SR and Lamanna, F and Kaessmann, H and Timoshevskiy, VA and Waterbury, CKM and Saraceno, C and Wiedemann, LM and Robb, SMC and Baker, C and Eichler, EE and Hockman, D and Sauka-Spengler, T and Yandell, M and Krumlauf, R and Elgar, G and Amemiya, CT}, title = {Publisher Correction: The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {768}, doi = {10.1038/s41588-018-0075-2}, pmid = {29674745}, issn = {1546-1718}, abstract = {In the version of this article initially published, the present addresses for authors Dorit Hockman and Chris Amemiya were switched. The error has been corrected in the HTML and PDF versions of the article.}, } @article {pmid29674744, year = {2018}, author = {Coll, F and Phelan, J and Hill-Cawthorne, GA and Nair, MB and Mallard, K and Ali, S and Abdallah, AM and Alghamdi, S and Alsomali, M and Ahmed, AO and Portelli, S and Oppong, Y and Alves, A and Bessa, TB and Campino, S and Caws, M and Chatterjee, A and Crampin, AC and Dheda, K and Furnham, N and Glynn, JR and Grandjean, L and Ha, DM and Hasan, R and Hasan, Z and Hibberd, ML and Joloba, M and Jones-López, EC and Matsumoto, T and Miranda, A and Moore, DJ and Mocillo, N and Panaiotov, S and Parkhill, J and Penha, C and Perdigão, J and Portugal, I and Rchiad, Z and Robledo, J and Sheen, P and Shesha, NT and Sirgel, FA and Sola, C and Sousa, EO and Streicher, EM and Van Helden, P and Viveiros, M and Warren, RM and McNerney, R and Pain, A and Clark, TG}, title = {Author Correction: Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {764}, doi = {10.1038/s41588-018-0074-3}, pmid = {29674744}, issn = {1546-1718}, abstract = {In the version of this article initially published, the URL listed for TubercuList was incorrect. The correct URL is https://mycobrowser.epfl.ch/. The error has been corrected in the HTML and PDF versions of the article.}, } @article {pmid29674597, year = {2018}, author = {Chhabra, A}, title = {Academia's forgotten footnote.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {350}, doi = {10.1126/science.360.6386.350}, pmid = {29674597}, issn = {1095-9203}, } @article {pmid29674596, year = {2018}, author = {Rocha, AG and Franco, A and Krezel, AM and Rumsey, JM and Alberti, JM and Knight, WC and Biris, N and Zacharioudakis, E and Janetka, JW and Baloh, RH and Kitsis, RN and Mochly-Rosen, D and Townsend, RR and Gavathiotis, E and Dorn, GW}, title = {MFN2 agonists reverse mitochondrial defects in preclinical models of Charcot-Marie-Tooth disease type 2A.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {336-341}, pmid = {29674596}, issn = {1095-9203}, support = {R35 HL135736/HL/NHLBI NIH HHS/United States ; R01 HL128071/HL/NHLBI NIH HHS/United States ; P41 GM103422/GM/NIGMS NIH HHS/United States ; R01 CA178394/CA/NCI NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; P30 CA013330/CA/NCI NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Animals ; Arginine/genetics ; Axons/drug effects/physiology ; Charcot-Marie-Tooth Disease/*drug therapy/genetics ; Disease Models, Animal ; *Drug Design ; GTP Phosphohydrolases/genetics/metabolism ; Glutamine/genetics ; Humans ; Methionine/genetics ; Mice ; Mice, Inbred C57BL ; Mitochondria/*drug effects ; Mitochondrial Diseases/*drug therapy ; Mitochondrial Proteins/*agonists/genetics/metabolism ; Oligopeptides/chemistry/*pharmacology/therapeutic use ; Phosphorylation ; Protein Kinases/metabolism ; Sciatic Nerve/drug effects/physiopathology ; Small Molecule Libraries/*pharmacology/therapeutic use ; Threonine/genetics ; }, abstract = {Mitofusins (MFNs) promote fusion-mediated mitochondrial content exchange and subcellular trafficking. Mutations in Mfn2 cause neurodegenerative Charcot-Marie-Tooth disease type 2A (CMT2A). We showed that MFN2 activity can be determined by Met376 and His380 interactions with Asp725 and Leu727 and controlled by PINK1 kinase-mediated phosphorylation of adjacent MFN2 Ser378 Small-molecule mimics of the peptide-peptide interface of MFN2 disrupted this interaction, allosterically activating MFN2 and promoting mitochondrial fusion. These first-in-class mitofusin agonists overcame dominant mitochondrial defects provoked in cultured neurons by CMT2A mutants MFN2 Arg94→Gln94 and MFN2 Thr105→Met105, as demonstrated by amelioration of mitochondrial dysmotility, fragmentation, depolarization, and clumping. A mitofusin agonist normalized axonal mitochondrial trafficking within sciatic nerves of MFN2 Thr105→Met105 mice, promising a therapeutic approach for CMT2A and other untreatable diseases of impaired neuronal mitochondrial dynamism and/or trafficking.}, } @article {pmid29674595, year = {2018}, author = {Filbin, MG and Tirosh, I and Hovestadt, V and Shaw, ML and Escalante, LE and Mathewson, ND and Neftel, C and Frank, N and Pelton, K and Hebert, CM and Haberler, C and Yizhak, K and Gojo, J and Egervari, K and Mount, C and van Galen, P and Bonal, DM and Nguyen, QD and Beck, A and Sinai, C and Czech, T and Dorfer, C and Goumnerova, L and Lavarino, C and Carcaboso, AM and Mora, J and Mylvaganam, R and Luo, CC and Peyrl, A and Popović, M and Azizi, A and Batchelor, TT and Frosch, MP and Martinez-Lage, M and Kieran, MW and Bandopadhayay, P and Beroukhim, R and Fritsch, G and Getz, G and Rozenblatt-Rosen, O and Wucherpfennig, KW and Louis, DN and Monje, M and Slavc, I and Ligon, KL and Golub, TR and Regev, A and Bernstein, BE and Suvà, ML}, title = {Developmental and oncogenic programs in H3K27M gliomas dissected by single-cell RNA-seq.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {331-335}, pmid = {29674595}, issn = {1095-9203}, support = {R01 CA188228/CA/NCI NIH HHS/United States ; DP1 CA216873/CA/NCI NIH HHS/United States ; U24 CA180922/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; P01 CA142536/CA/NCI NIH HHS/United States ; K12 CA090354/CA/NCI NIH HHS/United States ; S10 RR023440/RR/NCRR NIH HHS/United States ; R33 CA202820/CA/NCI NIH HHS/United States ; R01 CA219943/CA/NCI NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; }, mesh = {Brain Neoplasms/genetics/*pathology ; Carcinogenesis/*genetics ; Cell Proliferation ; Glioma/genetics/*pathology ; Histones/metabolism ; Humans ; Mitogen-Activated Protein Kinase 7/genetics ; Mutation ; Oligodendroglia/*metabolism/*pathology ; *Oncogenes ; Receptor, Platelet-Derived Growth Factor alpha/genetics/metabolism ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; }, abstract = {Gliomas with histone H3 lysine27-to-methionine mutations (H3K27M-glioma) arise primarily in the midline of the central nervous system of young children, suggesting a cooperation between genetics and cellular context in tumorigenesis. Although the genetics of H3K27M-glioma are well characterized, their cellular architecture remains uncharted. We performed single-cell RNA sequencing in 3321 cells from six primary H3K27M-glioma and matched models. We found that H3K27M-glioma primarily contain cells that resemble oligodendrocyte precursor cells (OPC-like), whereas more differentiated malignant cells are a minority. OPC-like cells exhibit greater proliferation and tumor-propagating potential than their more differentiated counterparts and are at least in part sustained by PDGFRA signaling. Our study characterizes oncogenic and developmental programs in H3K27M-glioma at single-cell resolution and across genetic subclones, suggesting potential therapeutic targets in this disease.}, } @article {pmid29674594, year = {2018}, author = {Brandler, WM and Antaki, D and Gujral, M and Kleiber, ML and Whitney, J and Maile, MS and Hong, O and Chapman, TR and Tan, S and Tandon, P and Pang, T and Tang, SC and Vaux, KK and Yang, Y and Harrington, E and Juul, S and Turner, DJ and Thiruvahindrapuram, B and Kaur, G and Wang, Z and Kingsmore, SF and Gleeson, JG and Bisson, D and Kakaradov, B and Telenti, A and Venter, JC and Corominas, R and Toma, C and Cormand, B and Rueda, I and Guijarro, S and Messer, KS and Nievergelt, CM and Arranz, MJ and Courchesne, E and Pierce, K and Muotri, AR and Iakoucheva, LM and Hervas, A and Scherer, SW and Corsello, C and Sebat, J}, title = {Paternally inherited cis-regulatory structural variants are associated with autism.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {327-331}, doi = {10.1126/science.aan2261}, pmid = {29674594}, issn = {1095-9203}, support = {R01 MH076431/MH/NIMH NIH HHS/United States ; R01 MH108528/MH/NIMH NIH HHS/United States ; R21 MH104766/MH/NIMH NIH HHS/United States ; R01 MH110558/MH/NIMH NIH HHS/United States ; R01 MH109885/MH/NIMH NIH HHS/United States ; P50 MH081755/MH/NIMH NIH HHS/United States ; R01 MH105524/MH/NIMH NIH HHS/United States ; T32 GM008666/GM/NIGMS NIH HHS/United States ; U19 HD077693/HD/NICHD NIH HHS/United States ; R01 MH113715/MH/NIMH NIH HHS/United States ; }, mesh = {Autism Spectrum Disorder/*genetics ; Exons ; Gene Expression Regulation ; *Genetic Predisposition to Disease ; *Genetic Variation ; Genome, Human ; Humans ; Mutation ; *Paternal Inheritance ; Pedigree ; Promoter Regions, Genetic/*genetics ; RNA, Untranslated/genetics ; Selection, Genetic ; Sequence Deletion ; Transcription Factors/genetics ; }, abstract = {The genetic basis of autism spectrum disorder (ASD) is known to consist of contributions from de novo mutations in variant-intolerant genes. We hypothesize that rare inherited structural variants in cis-regulatory elements (CRE-SVs) of these genes also contribute to ASD. We investigated this by assessing the evidence for natural selection and transmission distortion of CRE-SVs in whole genomes of 9274 subjects from 2600 families affected by ASD. In a discovery cohort of 829 families, structural variants were depleted within promoters and untranslated regions, and paternally inherited CRE-SVs were preferentially transmitted to affected offspring and not to their unaffected siblings. The association of paternal CRE-SVs was replicated in an independent sample of 1771 families. Our results suggest that rare inherited noncoding variants predispose children to ASD, with differing contributions from each parent.}, } @article {pmid29674593, year = {2018}, author = {Reich, PB and Hobbie, SE and Lee, TD and Pastore, MA}, title = {Unexpected reversal of C3 versus C4 grass response to elevated CO2 during a 20-year field experiment.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {317-320}, doi = {10.1126/science.aas9313}, pmid = {29674593}, issn = {1095-9203}, mesh = {Biomass ; *Carbon Cycle ; Carbon Dioxide/*metabolism ; Climate Change ; Nitrogen Fixation ; *Photosynthesis ; Poaceae/*metabolism ; }, abstract = {Theory predicts and evidence shows that plant species that use the C4 photosynthetic pathway (C4 species) are less responsive to elevated carbon dioxide (eCO2) than species that use only the C3 pathway (C3 species). We document a reversal from this expected C3-C4 contrast. Over the first 12 years of a 20-year free-air CO2 enrichment experiment with 88 C3 or C4 grassland plots, we found that biomass was markedly enhanced at eCO2 relative to ambient CO2 in C3 but not C4 plots, as expected. During the subsequent 8 years, the pattern reversed: Biomass was markedly enhanced at eCO2 relative to ambient CO2 in C4 but not C3 plots. Soil net nitrogen mineralization rates, an index of soil nitrogen supply, exhibited a similar shift: eCO2 first enhanced but later depressed rates in C3 plots, with the opposite true in C4 plots, partially explaining the reversal of the eCO2 biomass response. These findings challenge the current C3-C4eCO2 paradigm and show that even the best-supported short-term drivers of plant response to global change might not predict long-term results.}, } @article {pmid29674592, year = {2018}, author = {Ohtaka-Maruyama, C and Okamoto, M and Endo, K and Oshima, M and Kaneko, N and Yura, K and Okado, H and Miyata, T and Maeda, N}, title = {Synaptic transmission from subplate neurons controls radial migration of neocortical neurons.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {313-317}, doi = {10.1126/science.aar2866}, pmid = {29674592}, issn = {1095-9203}, mesh = {Animals ; Cell Communication ; *Cell Movement ; Gene Knock-In Techniques ; Mice ; Neocortex/*cytology/*embryology ; *Neurogenesis ; Neurons/cytology/metabolism/*physiology ; Receptors, N-Methyl-D-Aspartate/metabolism ; *Synaptic Transmission ; Tetanus Toxin/genetics ; }, abstract = {The neocortex exhibits a six-layered structure that is formed by radial migration of excitatory neurons, for which the multipolar-to-bipolar transition of immature migrating multipolar neurons is required. Here, we report that subplate neurons, one of the first neuron types born in the neocortex, manage the multipolar-to-bipolar transition of migrating neurons. By histochemical, imaging, and microarray analyses on the mouse embryonic cortex, we found that subplate neurons extend neurites toward the ventricular side of the subplate and form transient glutamatergic synapses on the multipolar neurons just below the subplate. NMDAR (N-methyl-d-aspartate receptor)-mediated synaptic transmission from subplate neurons to multipolar neurons induces the multipolar-to-bipolar transition, leading to a change in migration mode from slow multipolar migration to faster radial glial-guided locomotion. Our data suggested that transient synapses formed on early immature neurons regulate radial migration.}, } @article {pmid29674591, year = {2018}, author = {Smith, FA and Elliott Smith, RE and Lyons, SK and Payne, JL}, title = {Body size downgrading of mammals over the late Quaternary.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {310-313}, doi = {10.1126/science.aao5987}, pmid = {29674591}, issn = {1095-9203}, mesh = {Animals ; *Biological Evolution ; *Body Size ; *Extinction, Biological ; Fossils ; Hominidae/*physiology ; Humans ; }, abstract = {Since the late Pleistocene, large-bodied mammals have been extirpated from much of Earth. Although all habitable continents once harbored giant mammals, the few remaining species are largely confined to Africa. This decline is coincident with the global expansion of hominins over the late Quaternary. Here, we quantify mammalian extinction selectivity, continental body size distributions, and taxonomic diversity over five time periods spanning the past 125,000 years and stretching approximately 200 years into the future. We demonstrate that size-selective extinction was already under way in the oldest interval and occurred on all continents, within all trophic modes, and across all time intervals. Moreover, the degree of selectivity was unprecedented in 65 million years of mammalian evolution. The distinctive selectivity signature implicates hominin activity as a primary driver of taxonomic losses and ecosystem homogenization. Because megafauna have a disproportionate influence on ecosystem structure and function, past and present body size downgrading is reshaping Earth's biosphere.}, } @article {pmid29674590, year = {2018}, author = {Dedovets, D and Monteux, C and Deville, S}, title = {Five-dimensional imaging of freezing emulsions with solute effects.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {303-306}, doi = {10.1126/science.aar4503}, pmid = {29674590}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The interaction of objects with a moving solidification front is a common feature of many industrial and natural processes such as metal processing, the growth of single crystals, the cryopreservation of cells, or the formation of sea ice. Interaction of solidification fronts with objects leads to different outcomes, from total rejection of the objects to their complete engulfment. We imaged the freezing of emulsions in five dimensions (space, time, and solute concentration) with confocal microscopy. We showed that the solute induces long-range interactions that determine the solidification microstructure. The local increase of solute concentration enhances premelting, which controls the engulfment of droplets by the front and the evolution of grain boundaries. Freezing emulsions may be a good analog of many solidification systems where objects interact with a solidification interface.}, } @article {pmid29674589, year = {2018}, author = {Banerjee, A and Bernoulli, D and Zhang, H and Yuen, MF and Liu, J and Dong, J and Ding, F and Lu, J and Dao, M and Zhang, W and Lu, Y and Suresh, S}, title = {Ultralarge elastic deformation of nanoscale diamond.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {300-302}, doi = {10.1126/science.aar4165}, pmid = {29674589}, issn = {1095-9203}, abstract = {Diamonds have substantial hardness and durability, but attempting to deform diamonds usually results in brittle fracture. We demonstrate ultralarge, fully reversible elastic deformation of nanoscale (~300 nanometers) single-crystalline and polycrystalline diamond needles. For single-crystalline diamond, the maximum tensile strains (up to 9%) approached the theoretical elastic limit, and the corresponding maximum tensile stress reached ~89 to 98 gigapascals. After combining systematic computational simulations and characterization of pre- and postdeformation structural features, we ascribe the concurrent high strength and large elastic strain to the paucity of defects in the small-volume diamond nanoneedles and to the relatively smooth surfaces compared with those of microscale and larger specimens. The discovery offers the potential for new applications through optimized design of diamond nanostructure, geometry, elastic strains, and physical properties.}, } @article {pmid29674588, year = {2018}, author = {Grandgeorge, P and Krins, N and Hourlier-Fargette, A and Laberty-Robert, C and Neukirch, S and Antkowiak, A}, title = {Capillarity-induced folds fuel extreme shape changes in thin wicked membranes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {296-299}, doi = {10.1126/science.aaq0677}, pmid = {29674588}, issn = {1095-9203}, abstract = {Soft deformable materials are needed for applications such as stretchable electronics, smart textiles, or soft biomedical devices. However, the design of a durable, cost-effective, or biologically compatible version of such a material remains challenging. Living animal cells routinely cope with extreme deformations by unfolding preformed membrane reservoirs available in the form of microvilli or membrane folds. We synthetically mimicked this behavior by creating nanofibrous liquid-infused tissues that spontaneously form similar reservoirs through capillarity-induced folding. By understanding the physics of membrane buckling within the liquid film, we developed proof-of-concept conformable chemical surface treatments and stretchable basic electronic circuits.}, } @article {pmid29674587, year = {2018}, author = {Alcaraz Iranzo, D and Nanot, S and Dias, EJC and Epstein, I and Peng, C and Efetov, DK and Lundeberg, MB and Parret, R and Osmond, J and Hong, JY and Kong, J and Englund, DR and Peres, NMR and Koppens, FHL}, title = {Probing the ultimate plasmon confinement limits with a van der Waals heterostructure.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {291-295}, doi = {10.1126/science.aar8438}, pmid = {29674587}, issn = {1095-9203}, abstract = {The ability to confine light into tiny spatial dimensions is important for applications such as microscopy, sensing, and nanoscale lasers. Although plasmons offer an appealing avenue to confine light, Landau damping in metals imposes a trade-off between optical field confinement and losses. We show that a graphene-insulator-metal heterostructure can overcome that trade-off, and demonstrate plasmon confinement down to the ultimate limit of the length scale of one atom. This is achieved through far-field excitation of plasmon modes squeezed into an atomically thin hexagonal boron nitride dielectric spacer between graphene and metal rods. A theoretical model that takes into account the nonlocal optical response of both graphene and metal is used to describe the results. These ultraconfined plasmonic modes, addressed with far-field light excitation, enable a route to new regimes of ultrastrong light-matter interactions.}, } @article {pmid29674586, year = {2018}, author = {Phillips, KA and Trosman, JR and Deverka, PA and Quinn, B and Tunis, S and Neumann, PJ and Chambers, JD and Garrison, LP and Douglas, MP and Weldon, CB}, title = {Insurance coverage for genomic tests.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {278-279}, pmid = {29674586}, issn = {1095-9203}, support = {P30 CA082103/CA/NCI NIH HHS/United States ; R01 HG007063/HG/NHGRI NIH HHS/United States ; U01 HG009599/HG/NHGRI NIH HHS/United States ; }, mesh = {Genetic Testing/*economics ; Genomics/*economics ; Humans ; *Insurance Coverage ; Medicaid ; Medicare ; United States ; }, } @article {pmid29674585, year = {2018}, author = {Biggs, D and Smith, RJ and Adams, VM and Brink, H and Cook, CN and Cooney, R and Holden, MH and Maron, M and Phelps, J and Possingham, HP and Redford, KH and Scholes, RJ and Sutherland, WJ and Underwood, FM and Milner-Gulland, EJ}, title = {Response-Ivory crisis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {277-278}, doi = {10.1126/science.aat1596}, pmid = {29674585}, issn = {1095-9203}, mesh = {Animals ; *Commerce ; *Elephants ; Humans ; }, } @article {pmid29674584, year = {2018}, author = {Lenda, M and Skórka, P and Mazur, B and Ward, A and Wilson, K}, title = {Ivory crisis: Role of bioprinting technology.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {277}, doi = {10.1126/science.aat0925}, pmid = {29674584}, issn = {1095-9203}, mesh = {*Bioprinting ; Humans ; Printing, Three-Dimensional ; Regenerative Medicine ; Technology ; *Tissue Engineering ; Tissue Scaffolds ; }, } @article {pmid29674583, year = {2018}, author = {Sekar, N and Clark, W and Dobson, A and Coelho, PCF and Hannam, PM and Hepworth, R and Hsiang, S and Kahumbu, P and Lee, PC and Lindsay, K and Pereira, CL and Wasser, SK and Nowak, K}, title = {Ivory crisis: Growing no-trade consensus.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {276-277}, doi = {10.1126/science.aat1105}, pmid = {29674583}, issn = {1095-9203}, mesh = {Animals ; Commerce ; *Consensus ; *Elephants ; Humans ; }, } @article {pmid29674582, year = {2018}, author = {Schwartz, MA and Vestweber, D and Simons, M}, title = {A unifying concept in vascular health and disease.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {270-271}, doi = {10.1126/science.aat3470}, pmid = {29674582}, issn = {1095-9203}, support = {R01 HL135582/HL/NHLBI NIH HHS/United States ; }, mesh = {Blood Vessels/abnormalities/*pathology/*physiopathology ; Humans ; Neovascularization, Physiologic ; Vascular Diseases/*physiopathology ; *Vascular Remodeling ; }, } @article {pmid29674581, year = {2018}, author = {Walhout, AJM}, title = {If two deletions don't stop growth, try three.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {269-270}, doi = {10.1126/science.aat4667}, pmid = {29674581}, issn = {1095-9203}, } @article {pmid29674580, year = {2018}, author = {Arkinson, C and Walden, H}, title = {Parkin function in Parkinson's disease.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {267-268}, doi = {10.1126/science.aar6606}, pmid = {29674580}, issn = {1095-9203}, mesh = {Age of Onset ; Female ; Humans ; Models, Biological ; Mutation ; Parkinson Disease/genetics/*metabolism ; Protein Domains/genetics ; Protein Transport ; Ubiquitin/*metabolism ; Ubiquitin-Protein Ligases/chemistry/genetics/*metabolism ; *Ubiquitination/genetics ; }, } @article {pmid29674579, year = {2018}, author = {Schinder, AF and Lanuza, GM}, title = {Whispering neurons fuel cortical highways.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {265-266}, doi = {10.1126/science.aat4587}, pmid = {29674579}, issn = {1095-9203}, mesh = {Humans ; *Neurons ; }, } @article {pmid29674578, year = {2018}, author = {LLorca, J}, title = {On the quest for the strongest materials.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {264-265}, doi = {10.1126/science.aat5211}, pmid = {29674578}, issn = {1095-9203}, } @article {pmid29674577, year = {2018}, author = {Hovenden, M and Newton, P}, title = {Plant responses to CO2 are a question of time.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {263-264}, doi = {10.1126/science.aat2481}, pmid = {29674577}, issn = {1095-9203}, mesh = {*Carbon Dioxide ; Plant Leaves ; *Plants ; }, } @article {pmid29674576, year = {2018}, author = {Kojima, K and Booth, CM and Summermatter, K and Bennett, A and Heisz, M and Blacksell, SD and McKinney, M}, title = {Risk-based reboot for global lab biosafety.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {260-262}, doi = {10.1126/science.aar2231}, pmid = {29674576}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Containment of Biohazards/*standards ; Gloves, Protective ; Humans ; Laboratories/*standards ; Manuals as Topic ; Occupational Exposure/*prevention & control ; Personal Protective Equipment/*standards ; Protective Clothing/standards ; Risk ; World Health Organization ; }, } @article {pmid29674575, year = {2018}, author = {Hall, SS}, title = {Omen in the blood.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {254-258}, doi = {10.1126/science.360.6386.254}, pmid = {29674575}, issn = {1095-9203}, mesh = {Biomarkers/blood/metabolism ; Glomerulosclerosis, Focal Segmental/*blood/*metabolism ; Humans ; Urokinase-Type Plasminogen Activator/*blood/*metabolism ; }, } @article {pmid29674574, year = {2018}, author = {Price, M}, title = {Proposal to rescue postdocs from limbo draws darts.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {253}, doi = {10.1126/science.360.6386.253}, pmid = {29674574}, issn = {1095-9203}, mesh = {Academies and Institutes ; *Biomedical Research ; *Career Mobility ; United States ; Workforce ; }, } @article {pmid29674573, year = {2018}, author = {Wade, L}, title = {Ancient DNA untangles South Asian roots.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {252}, doi = {10.1126/science.360.6386.252}, pmid = {29674573}, issn = {1095-9203}, mesh = {Asia, Southeastern/ethnology ; Asian Continental Ancestry Group/*ethnology/*genetics ; *Biological Evolution ; *DNA, Ancient ; Humans ; }, } @article {pmid29674572, year = {2018}, author = {Mervis, J}, title = {Plan for 2020 U.S. census is fatally flawed, critics say.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {250-251}, doi = {10.1126/science.360.6386.250}, pmid = {29674572}, issn = {1095-9203}, } @article {pmid29674571, year = {2018}, author = {Lawler, A}, title = {Cannabis, opium use part of ancient Near Eastern cultures.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {249-250}, doi = {10.1126/science.360.6386.249}, pmid = {29674571}, issn = {1095-9203}, mesh = {Archaeology ; *Cannabis ; *Ceremonial Behavior ; Cyprus ; Drug Utilization/*history ; History, Ancient ; Humans ; Mesopotamia ; Middle East ; Opium/*history ; Papaver ; }, } @article {pmid29674570, year = {2018}, author = {Kintisch, E}, title = {Department of State's air pollution sensors go global.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {248-249}, doi = {10.1126/science.360.6386.248}, pmid = {29674570}, issn = {1095-9203}, mesh = {Air Pollution/*prevention & control ; China ; *Environmental Monitoring/instrumentation ; Humans ; Particulate Matter/*analysis/toxicity ; United States ; United States Government Agencies ; }, } @article {pmid29674569, year = {2018}, author = {Voosen, P}, title = {NASA lander to probe interior of Mars.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {247-248}, doi = {10.1126/science.360.6386.247}, pmid = {29674569}, issn = {1095-9203}, } @article {pmid29674568, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {244-246}, doi = {10.1126/science.360.6386.244}, pmid = {29674568}, issn = {1095-9203}, } @article {pmid29674567, year = {2018}, author = {Dror, IE}, title = {Biases in forensic experts.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {243}, doi = {10.1126/science.aat8443}, pmid = {29674567}, issn = {1095-9203}, mesh = {Bias ; Cognition ; *Forensic Medicine ; Humans ; Neurosciences ; *Social Justice ; }, } @article {pmid29674566, year = {2018}, author = {}, title = {Erratum for the Report "A precise measurement of the magnetic field in the corona of the black hole binary V404 Cygni" by Y. Dallilar, S. S. Eikenberry, A. Garner, R. D. Stelter, A. Gottlieb, P. Gandhi, P. Casella, V. S. Dhillon, T. R. Marsh, S. P. Littlefair, L. Hardy, R. Fender, K. Mooley, D. J. Walton, F. Fuerst, M. Bachetti, A. J. Castro-Tirado, M. Charcos, M. L. Edwards, N. M. Lasso-Cabrera, A. Marin-Franch, S. N. Raines, K. Ackley, J. G. Bennett, A. J. Cenarro, B. Chinn, H. V. Donoso, R. Frommeyer, K. Hanna, M. D. Herlevich, J. Julian, P. Miller, S. Mullin, C. H. Murphey, C. Packham, F. Varosi, C. Vega, C. Warner, A. N. Ramaprakash, M. Burse, S. Punnadi, P. Chordia, A. Gerarts, H. de Paz Martín, M. Martín Calero, R. Scarpa, S. Fernandez Acosta, W. M. Hernández Sánchez, B. Siegel, F. Francisco Pérez, H. D. Viera Martín, J. A. Rodríguez Losada, A. Nuñez, Á. Tejero, C. E. Martín González, C. Cabrera Rodríguez, J. Molgó, J. Esteban Rodriguez, J. I. Fernández Cáceres, L. A. Rodríguez García, M. Huertas Lopez, R. Dominguez, T. Gaggstatter, A. Cabrera Lavers, S. Geier, P. Pessev, A. Sarajedini.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {}, doi = {10.1126/science.aat9270}, pmid = {29674566}, issn = {1095-9203}, } @article {pmid29674565, year = {2018}, author = {Kuzmin, E and VanderSluis, B and Wang, W and Tan, G and Deshpande, R and Chen, Y and Usaj, M and Balint, A and Mattiazzi Usaj, M and van Leeuwen, J and Koch, EN and Pons, C and Dagilis, AJ and Pryszlak, M and Wang, JZY and Hanchard, J and Riggi, M and Xu, K and Heydari, H and San Luis, BJ and Shuteriqi, E and Zhu, H and Van Dyk, N and Sharifpoor, S and Costanzo, M and Loewith, R and Caudy, A and Bolnick, D and Brown, GW and Andrews, BJ and Boone, C and Myers, CL}, title = {Systematic analysis of complex genetic interactions.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {}, pmid = {29674565}, issn = {1095-9203}, support = {R01 HG005084/HG/NHGRI NIH HHS/United States ; R01 HG005853/HG/NHGRI NIH HHS/United States ; //CIHR/Canada ; //European Research Council/International ; R01 GM104975/GM/NIGMS NIH HHS/United States ; }, mesh = {*Gene Regulatory Networks ; Mutation ; Oligonucleotide Array Sequence Analysis ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*genetics ; }, abstract = {To systematically explore complex genetic interactions, we constructed ~200,000 yeast triple mutants and scored negative trigenic interactions. We selected double-mutant query genes across a broad spectrum of biological processes, spanning a range of quantitative features of the global digenic interaction network and tested for a genetic interaction with a third mutation. Trigenic interactions often occurred among functionally related genes, and essential genes were hubs on the trigenic network. Despite their functional enrichment, trigenic interactions tended to link genes in distant bioprocesses and displayed a weaker magnitude than digenic interactions. We estimate that the global trigenic interaction network is ~100 times as large as the global digenic network, highlighting the potential for complex genetic interactions to affect the biology of inheritance, including the genotype-to-phenotype relationship.}, } @article {pmid29674564, year = {2018}, author = {Liu, TL and Upadhyayula, S and Milkie, DE and Singh, V and Wang, K and Swinburne, IA and Mosaliganti, KR and Collins, ZM and Hiscock, TW and Shea, J and Kohrman, AQ and Medwig, TN and Dambournet, D and Forster, R and Cunniff, B and Ruan, Y and Yashiro, H and Scholpp, S and Meyerowitz, EM and Hockemeyer, D and Drubin, DG and Martin, BL and Matus, DQ and Koyama, M and Megason, SG and Kirchhausen, T and Betzig, E}, title = {Observing the cell in its native state: Imaging subcellular dynamics in multicellular organisms.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {}, pmid = {29674564}, issn = {1095-9203}, support = {R01 CA196884/CA/NCI NIH HHS/United States ; R35 GM118149/GM/NIGMS NIH HHS/United States ; R01 DC015478/DC/NIDCD NIH HHS/United States ; R00 CA154870/CA/NCI NIH HHS/United States ; R01 GM075252/GM/NIGMS NIH HHS/United States ; R25 GM103792/GM/NIGMS NIH HHS/United States ; R01 GM121597/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Movement ; Endocytosis ; Eye/ultrastructure ; Humans ; Imaging, Three-Dimensional/*methods ; Microscopy/*methods ; Mitosis ; Organelles ; Single-Cell Analysis ; Zebrafish ; }, abstract = {True physiological imaging of subcellular dynamics requires studying cells within their parent organisms, where all the environmental cues that drive gene expression, and hence the phenotypes that we actually observe, are present. A complete understanding also requires volumetric imaging of the cell and its surroundings at high spatiotemporal resolution, without inducing undue stress on either. We combined lattice light-sheet microscopy with adaptive optics to achieve, across large multicellular volumes, noninvasive aberration-free imaging of subcellular processes, including endocytosis, organelle remodeling during mitosis, and the migration of axons, immune cells, and metastatic cancer cells in vivo. The technology reveals the phenotypic diversity within cells across different organisms and developmental stages and may offer insights into how cells harness their intrinsic variability to adapt to different physiological environments.}, } @article {pmid29674455, year = {2018}, author = {Vontas, J and Grigoraki, L and Morgan, J and Tsakireli, D and Fuseini, G and Segura, L and Niemczura de Carvalho, J and Nguema, R and Weetman, D and Slotman, MA and Hemingway, J}, title = {Rapid selection of a pyrethroid metabolic enzyme CYP9K1 by operational malaria control activities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4619-4624}, pmid = {29674455}, issn = {1091-6490}, mesh = {Animals ; Anopheles/*drug effects/parasitology ; Cytochrome P-450 Enzyme System/*metabolism ; Equatorial Guinea/epidemiology ; Female ; Humans ; Insecticide Resistance ; Insecticides/*pharmacokinetics ; Islands/epidemiology ; Malaria/epidemiology/genetics/metabolism/*prevention & control ; Mosquito Control/methods ; Prevalence ; Pyrethrins/*pharmacokinetics ; }, abstract = {Since 2004, indoor residual spraying (IRS) and long-lasting insecticide-impregnated bednets (LLINs) have reduced the malaria parasite prevalence in children on Bioko Island, Equatorial Guinea, from 45% to 12%. After target site-based (knockdown resistance; kdr) pyrethroid resistance was detected in 2004 in Anopheles coluzzii (formerly known as the M form of the Anopheles gambiae complex), the carbamate bendiocarb was introduced. Subsequent analysis showed that kdr alone was not operationally significant, so pyrethroid-based IRS was successfully reintroduced in 2012. In 2007 and 2014-2015, mass distribution of new pyrethroid LLINs was undertaken to increase the net coverage levels. The combined selection pressure of IRS and LLINs resulted in an increase in the frequency of pyrethroid resistance in 2015. In addition to a significant increase in kdr frequency, an additional metabolic pyrethroid resistance mechanism had been selected. Increased metabolism of the pyrethroid deltamethrin was linked with up-regulation of the cytochrome P450 CYP9K1. The increase in resistance prompted a reversion to bendiocarb IRS in 2016 to avoid a resurgence of malaria, in line with the national Malaria Control Program plan.}, } @article {pmid29674454, year = {2018}, author = {Malia, PC and Numrich, J and Nishimura, T and González Montoro, A and Stefan, CJ and Ungermann, C}, title = {Control of vacuole membrane homeostasis by a resident PI-3,5-kinase inhibitor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4684-4689}, pmid = {29674454}, issn = {1091-6490}, support = {MC_UU_12018/6//Medical Research Council/United Kingdom ; }, mesh = {Carrier Proteins/genetics/*metabolism ; Intracellular Membranes/*metabolism ; Lysosomes/genetics/metabolism ; Phosphatidylinositol 3-Kinases/*antagonists & inhibitors/genetics/metabolism ; Phosphatidylinositol Phosphates/genetics/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/*antagonists & inhibitors/genetics/metabolism ; Saccharomyces cerevisiae/cytology/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/*antagonists & inhibitors/genetics/*metabolism ; Vacuoles/genetics/*metabolism ; rab GTP-Binding Proteins/genetics/metabolism ; }, abstract = {Lysosomes have an important role in cellular protein and organelle quality control, metabolism, and signaling. On the surface of lysosomes, the PIKfyve/Fab1 complex generates phosphatidylinositol 3,5-bisphosphate, PI-3,5-P2, which is critical for lysosomal membrane homeostasis during acute osmotic stress and for lysosomal signaling. Here, we identify the inverted BAR protein Ivy1 as an inhibitor of the Fab1 complex with a direct influence on PI-3,5-P2 levels and vacuole homeostasis. Ivy1 requires Ypt7 binding for its function, binds PI-3,5-P2, and interacts with the Fab1 kinase. Colocalization of Ivy1 and Fab1 is lost during osmotic stress. In agreement with Ivy1's role as a Fab1 regulator, its overexpression blocks Fab1 activity during osmotic shock and vacuole fragmentation. Conversely, loss of Ivy1, or lateral relocalization of Ivy1 on vacuoles away from Fab1, results in vacuole fragmentation and poor growth. Our data suggest that Ivy1 modulates Fab1-mediated PI-3,5-P2 synthesis during membrane stress and may allow adjustment of the vacuole membrane environment.}, } @article {pmid29674453, year = {2018}, author = {Li, Z and Tiley, GP and Galuska, SR and Reardon, CR and Kidder, TI and Rundell, RJ and Barker, MS}, title = {Multiple large-scale gene and genome duplications during the evolution of hexapods.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4713-4718}, pmid = {29674453}, issn = {1091-6490}, mesh = {Animals ; *Evolution, Molecular ; *Gene Duplication ; *Genome, Insect ; Insecta/*genetics ; *Phylogeny ; }, abstract = {Polyploidy or whole genome duplication (WGD) is a major contributor to genome evolution and diversity. Although polyploidy is recognized as an important component of plant evolution, it is generally considered to play a relatively minor role in animal evolution. Ancient polyploidy is found in the ancestry of some animals, especially fishes, but there is little evidence for ancient WGDs in other metazoan lineages. Here we use recently published transcriptomes and genomes from more than 150 species across the insect phylogeny to investigate whether ancient WGDs occurred during the evolution of Hexapoda, the most diverse clade of animals. Using gene age distributions and phylogenomics, we found evidence for 18 ancient WGDs and six other large-scale bursts of gene duplication during insect evolution. These bursts of gene duplication occurred in the history of lineages such as the Lepidoptera, Trichoptera, and Odonata. To further corroborate the nature of these duplications, we evaluated the pattern of gene retention from putative WGDs observed in the gene age distributions. We found a relatively strong signal of convergent gene retention across many of the putative insect WGDs. Considering the phylogenetic breadth and depth of the insect phylogeny, this observation is consistent with polyploidy as we expect dosage balance to drive the parallel retention of genes. Together with recent research on plant evolution, our hexapod results suggest that genome duplications contributed to the evolution of two of the most diverse lineages of eukaryotes on Earth.}, } @article {pmid29674452, year = {2018}, author = {Nath, P and Ganguly, S and Horbach, J and Sollich, P and Karmakar, S and Sengupta, S}, title = {On the existence of thermodynamically stable rigid solids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4322-E4329}, pmid = {29674452}, issn = {1091-6490}, abstract = {Customarily, crystalline solids are defined to be rigid since they resist changes of shape determined by their boundaries. However, rigid solids cannot exist in the thermodynamic limit where boundaries become irrelevant. Particles in the solid may rearrange to adjust to shape changes eliminating stress without destroying crystalline order. Rigidity is therefore valid only in the metastable state that emerges because these particle rearrangements in response to a deformation, or strain, are associated with slow collective processes. Here, we show that a thermodynamic collective variable may be used to quantify particle rearrangements that occur as a solid is deformed at zero strain rate. Advanced Monte Carlo simulation techniques are then used to obtain the equilibrium free energy as a function of this variable. Our results lead to a unique view on rigidity: While at zero strain a rigid crystal coexists with one that responds to infinitesimal strain by rearranging particles and expelling stress, at finite strain the rigid crystal is metastable, associated with a free energy barrier that decreases with increasing strain. The rigid phase becomes thermodynamically stable when an external field, which penalizes particle rearrangements, is switched on. This produces a line of first-order phase transitions in the field-strain plane that intersects the origin. Failure of a solid once strained beyond its elastic limit is associated with kinetic decay processes of the metastable rigid crystal deformed with a finite strain rate. These processes can be understood in quantitative detail using our computed phase diagram as reference.}, } @article {pmid29674451, year = {2018}, author = {Lee, G and Espirito Santo, AI and Zwingenberger, S and Cai, L and Vogl, T and Feldmann, M and Horwood, NJ and Chan, JK and Nanchahal, J}, title = {Fully reduced HMGB1 accelerates the regeneration of multiple tissues by transitioning stem cells to GAlert.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4463-E4472}, pmid = {29674451}, issn = {1091-6490}, support = {MR/K007939/1//Medical Research Council/United Kingdom ; 21190//Arthritis Research UK/United Kingdom ; }, mesh = {Animals ; *Cell Cycle ; Cells, Cultured ; Chemokine CXCL12/metabolism ; Fractures, Bone/*therapy ; HMGB1 Protein/*physiology ; Hematopoietic Stem Cells/*cytology/physiology ; Humans ; Mice ; Mice, Knockout ; Muscle, Skeletal/*cytology/physiology ; Osteogenesis ; Receptors, CXCR4/metabolism ; *Regeneration ; Signal Transduction ; Wound Healing ; }, abstract = {A major discovery of recent decades has been the existence of stem cells and their potential to repair many, if not most, tissues. With the aging population, many attempts have been made to use exogenous stem cells to promote tissue repair, so far with limited success. An alternative approach, which may be more effective and far less costly, is to promote tissue regeneration by targeting endogenous stem cells. However, ways of enhancing endogenous stem cell function remain poorly defined. Injury leads to the release of danger signals which are known to modulate the immune response, but their role in stem cell-mediated repair in vivo remains to be clarified. Here we show that high mobility group box 1 (HMGB1) is released following fracture in both humans and mice, forms a heterocomplex with CXCL12, and acts via CXCR4 to accelerate skeletal, hematopoietic, and muscle regeneration in vivo. Pretreatment with HMGB1 2 wk before injury also accelerated tissue regeneration, indicating an acquired proregenerative signature. HMGB1 led to sustained increase in cell cycling in vivo, and using Hmgb1-/- mice we identified the underlying mechanism as the transition of multiple quiescent stem cells from G0 to GAlert HMGB1 also transitions human stem and progenitor cells to GAlert Therefore, exogenous HMGB1 may benefit patients in many clinical scenarios, including trauma, chemotherapy, and elective surgery.}, } @article {pmid29674450, year = {2018}, author = {Spies, I and Hauser, L and Jorde, PE and Knutsen, H and Punt, AE and Rogers, LA and Stenseth, NC}, title = {Inferring genetic connectivity in real populations, exemplified by coastal and oceanic Atlantic cod.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4945-4950}, pmid = {29674450}, issn = {1091-6490}, mesh = {*Animal Migration ; Animals ; Female ; Gadus morhua/*genetics ; *Genetic Variation ; Male ; *Models, Genetic ; *Selection, Genetic ; }, abstract = {Genetic data are commonly used to estimate connectivity between putative populations, but translating them to demographic dispersal rates is complicated. Theoretical equations that infer a migration rate based on the genetic estimator FST , such as Wright's equation, FST ≈ 1/(4Nem + 1), make assumptions that do not apply to most real populations. How complexities inherent to real populations affect migration was exemplified by Atlantic cod in the North Sea and Skagerrak and was examined within an age-structured model that incorporated genetic markers. Migration was determined under various scenarios by varying the number of simulated migrants until the mean simulated level of genetic differentiation matched a fixed level of genetic differentiation equal to empirical estimates. Parameters that decreased the Ne /Nt ratio (where Ne is the effective and Nt is the total population size), such as high fishing mortality and high fishing gear selectivity, increased the number of migrants required to achieve empirical levels of genetic differentiation. Higher maturity-at-age and lower selectivity increased Ne /Nt and decreased migration when genetic differentiation was fixed. Changes in natural mortality, fishing gear selectivity, and maturity-at-age within expected limits had a moderate effect on migration when genetic differentiation was held constant. Changes in population size had the greatest effect on the number of migrants to achieve fixed levels of FST , particularly when genetic differentiation was low, FST ≈ 10-3 Highly variable migration patterns, compared with constant migration, resulted in higher variance in genetic differentiation and higher extreme values. Results are compared with and provide insight into the use of theoretical equations to estimate migration among real populations.}, } @article {pmid29674449, year = {2018}, author = {Wu, L and Zhang, H and Jiang, Y and Gallo, RC and Cheng, H}, title = {Induction of antitumor cytotoxic lymphocytes using engineered human primary blood dendritic cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4453-E4462}, pmid = {29674449}, issn = {1091-6490}, mesh = {Animals ; Antigens, Neoplasm/immunology/metabolism ; Apoptosis ; Cell Proliferation ; Cells, Cultured ; Cytotoxicity, Immunologic/*immunology ; Dendritic Cells/cytology/*immunology/transplantation ; Humans ; Interferon-gamma/metabolism ; Leukocytes, Mononuclear/*cytology ; Lung Neoplasms/*immunology/*prevention & control/secondary ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Neoplasm Proteins/immunology/metabolism ; T-Lymphocytes, Cytotoxic/*immunology ; Tissue Engineering ; Xenograft Model Antitumor Assays ; }, abstract = {Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+/CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs). In an autologous setting, the HLA-A2+ ihv-DCs that present hTERT antigen prime autologous T cells to generate hTERT-specific CTLs, inducing cytolysis of hTERT-expressing target cells in an HLA-A2-restricted manner. Remarkably, ihv-DCs that carry two allogeneic HLA-DRB1 alleles are able to prime autologous T cells to proliferate robustly in generating HLA-A2-restricted, hTERT-specific CTLs. The ihv-DCs, which are engineered to express MAGEA3 and high levels of 4-1BBL and MICA, induce simultaneous production of both HLA-A2-restricted, MAGEA3-specific CTLs and NK cells from HLA-A2+ donor peripheral blood mononuclear cells. These cytotoxic lymphocytes suppress lung metastasis of A549/A2.1 lung cancer cells in NSG mice. Both CTLs and NK cells are found to infiltrate lung as well as lymphoid tissues, mimicking the in vivo trafficking patterns of cytotoxic lymphocytes. This approach should facilitate the development of cell-based immunotherapy for human lung cancer.}, } @article {pmid29674448, year = {2018}, author = {Xiang, B and Ribeiro, RF and Dunkelberger, AD and Wang, J and Li, Y and Simpkins, BS and Owrutsky, JC and Yuen-Zhou, J and Xiong, W}, title = {Two-dimensional infrared spectroscopy of vibrational polaritons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4845-4850}, doi = {10.1073/pnas.1722063115}, pmid = {29674448}, issn = {1091-6490}, abstract = {We report experimental 2D infrared (2D IR) spectra of coherent light-matter excitations--molecular vibrational polaritons. The application of advanced 2D IR spectroscopy to vibrational polaritons challenges and advances our understanding in both fields. First, the 2D IR spectra of polaritons differ drastically from free uncoupled excitations and a new interpretation is needed. Second, 2D IR uniquely resolves excitation of hybrid light-matter polaritons and unexpected dark states in a state-selective manner, revealing otherwise hidden interactions between them. Moreover, 2D IR signals highlight the impact of molecular anharmonicities which are applicable to virtually all molecular systems. A quantum-mechanical model is developed which incorporates both nuclear and electrical anharmonicities and provides the basis for interpreting this class of 2D IR spectra. This work lays the foundation for investigating phenomena of nonlinear photonics and chemistry of molecular vibrational polaritons which cannot be probed with traditional linear spectroscopy.}, } @article {pmid29674447, year = {2018}, author = {Zmigrod, L and Rentfrow, PJ and Robbins, TW}, title = {Cognitive underpinnings of nationalistic ideology in the context of Brexit.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4532-E4540}, pmid = {29674447}, issn = {1091-6490}, mesh = {Adult ; *Authoritarianism ; Cognition/*physiology ; European Union ; Female ; Humans ; Individuality ; Male ; *Politics ; *Psychology ; United Kingdom ; }, abstract = {Nationalistic identities often play an influential role in citizens' voting behavior and political engagement. Nationalistic ideologies tend to have firm categories and rules for what belongs to and represents the national culture. In a sample of 332 UK citizens, we tested whether strict categorization of stimuli and rules in objective cognitive tasks would be evident in strongly nationalistic individuals. Using voting behavior and attitudes from the United Kingdom's 2016 EU referendum, we found that a flexible representation of national identity and culture was linked to cognitive flexibility in the ideologically neutral Wisconsin Card Sorting Test and Remote Associates Test, and to self-reported flexibility under uncertainty. Path analysis revealed that subjective and objective cognitive inflexibility predicted heightened authoritarianism, nationalism, conservatism, and system justification, and these in turn were predictive of support for Brexit and opposition to immigration, the European Union, and free movement of labor. This model accounted for 47.6% of the variance in support for Brexit. Path analysis models were also predictive of participants' sense of personal attachment to the United Kingdom, signifying that individual differences in cognitive flexibility may contribute toward ideological thinking styles that shape both nationalistic attitudes and personal sense of nationalistic identity. These findings further suggest that emotionally neutral "cold" cognitive information processing-and not just "hot" emotional cognition-may play a key role in ideological behavior and identity.}, } @article {pmid29674446, year = {2018}, author = {Lenman, A and Liaci, AM and Liu, Y and Frängsmyr, L and Frank, M and Blaum, BS and Chai, W and Podgorski, II and Harrach, B and Benkő, M and Feizi, T and Stehle, T and Arnberg, N}, title = {Polysialic acid is a cellular receptor for human adenovirus 52.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4264-E4273}, pmid = {29674446}, issn = {1091-6490}, support = {WT093378MA/Z/10/Z//Wellcome Trust/United Kingdom ; WT099197/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adenoviruses, Human/*chemistry/metabolism ; Cell Line, Tumor ; Humans ; *Molecular Dynamics Simulation ; Sialic Acids/*chemistry/metabolism ; }, abstract = {Human adenovirus 52 (HAdV-52) is one of only three known HAdVs equipped with both a long and a short fiber protein. While the long fiber binds to the coxsackie and adenovirus receptor, the function of the short fiber in the virus life cycle is poorly understood. Here, we show, by glycan microarray analysis and cellular studies, that the short fiber knob (SFK) of HAdV-52 recognizes long chains of α-2,8-linked polysialic acid (polySia), a large posttranslational modification of selected carrier proteins, and that HAdV-52 can use polySia as a receptor on target cells. X-ray crystallography, NMR, molecular dynamics simulation, and structure-guided mutagenesis of the SFK reveal that the nonreducing, terminal sialic acid of polySia engages the protein with direct contacts, and that specificity for polySia is achieved through subtle, transient electrostatic interactions with additional sialic acid residues. In this study, we present a previously unrecognized role for polySia as a cellular receptor for a human viral pathogen. Our detailed analysis of the determinants of specificity for this interaction has general implications for protein-carbohydrate interactions, particularly concerning highly charged glycan structures, and provides interesting dimensions on the biology and evolution of members of Human mastadenovirus G.}, } @article {pmid29674445, year = {2018}, author = {Wang, J and Wang, Y and Cui, WW and Huang, Y and Yang, Y and Liu, Y and Zhao, WS and Cheng, XY and Sun, WS and Cao, P and Zhu, MX and Wang, R and Hattori, M and Yu, Y}, title = {Druggable negative allosteric site of P2X3 receptors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4939-4944}, pmid = {29674445}, issn = {1091-6490}, mesh = {Allosteric Regulation ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; *Models, Molecular ; Phenyl Ethers/*chemistry ; Protein Domains ; Pyrimidines/*chemistry ; Receptors, Purinergic P2X3/*chemistry ; }, abstract = {Allosteric modulation provides exciting opportunities for drug discovery of enzymes, ion channels, and G protein-coupled receptors. As cation channels gated by extracellular ATP, P2X receptors have attracted wide attention as new drug targets. Although small molecules targeting P2X receptors have entered into clinical trials for rheumatoid arthritis, cough, and pain, negative allosteric modulation of these receptors remains largely unexplored. Here, combining X-ray crystallography, computational modeling, and functional studies of channel mutants, we identified a negative allosteric site on P2X3 receptors, fostered by the left flipper (LF), lower body (LB), and dorsal fin (DF) domains. Using two structurally analogous subtype-specific allosteric inhibitors of P2X3, AF-353 and AF-219, the latter being a drug candidate under phase II clinical trials for refractory chronic cough and idiopathic pulmonary fibrosis, we defined the molecular interactions between the drugs and receptors and the mechanism by which allosteric changes in the LF, DF, and LB domains modulate ATP activation of P2X3. Our detailed characterization of this druggable allosteric site should inspire new strategies to develop P2X3-specific allosteric modulators for clinical use.}, } @article {pmid29674434, year = {2018}, author = {Schumer, M and Xu, C and Powell, DL and Durvasula, A and Skov, L and Holland, C and Blazier, JC and Sankararaman, S and Andolfatto, P and Rosenthal, GG and Przeworski, M}, title = {Natural selection interacts with recombination to shape the evolution of hybrid genomes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {656-660}, pmid = {29674434}, issn = {1095-9203}, support = {R01 GM083098/GM/NIGMS NIH HHS/United States ; R35 GM125055/GM/NIGMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; Chimera/*genetics ; *Epistasis, Genetic ; *Evolution, Molecular ; Fishes ; Hybridization, Genetic ; *Recombination, Genetic ; *Selection, Genetic ; }, abstract = {To investigate the consequences of hybridization between species, we studied three replicate hybrid populations that formed naturally between two swordtail fish species, estimating their fine-scale genetic map and inferring ancestry along the genomes of 690 individuals. In all three populations, ancestry from the "minor" parental species is more common in regions of high recombination and where there is linkage to fewer putative targets of selection. The same patterns are apparent in a reanalysis of human and archaic admixture. These results support models in which ancestry from the minor parental species is more likely to persist when rapidly uncoupled from alleles that are deleterious in hybrids. Our analyses further indicate that selection on swordtail hybrids stems predominantly from deleterious combinations of epistatically interacting alleles.}, } @article {pmid29674433, year = {2018}, author = {Yang, MM and Kim, DJ and Alexe, M}, title = {Flexo-photovoltaic effect.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {904-907}, doi = {10.1126/science.aan3256}, pmid = {29674433}, issn = {1095-9203}, abstract = {It is highly desirable to discover photovoltaic mechanisms that enable enhanced efficiency of solar cells. Here we report that the bulk photovoltaic effect, which is free from the thermodynamic Shockley-Queisser limit but usually manifested only in noncentrosymmetric (piezoelectric or ferroelectric) materials, can be realized in any semiconductor, including silicon, by mediation of flexoelectric effect. We used either an atomic force microscope or a micrometer-scale indentation system to introduce strain gradients, thus creating very large photovoltaic currents from centrosymmetric single crystals of strontium titanate, titanium dioxide, and silicon. This strain gradient-induced bulk photovoltaic effect, which we call the flexo-photovoltaic effect, functions in the absence of a p-n junction. This finding may extend present solar cell technologies by boosting the solar energy conversion efficiency from a wide pool of established semiconductors.}, } @article {pmid29674432, year = {2018}, author = {Plass, M and Solana, J and Wolf, FA and Ayoub, S and Misios, A and Glažar, P and Obermayer, B and Theis, FJ and Kocks, C and Rajewsky, N}, title = {Cell type atlas and lineage tree of a whole complex animal by single-cell transcriptomics.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, doi = {10.1126/science.aaq1723}, pmid = {29674432}, issn = {1095-9203}, mesh = {Animals ; *Atlases as Topic ; Cell Differentiation/genetics ; Cell Lineage/*genetics ; Cells/*classification/metabolism ; Gene Expression Profiling/*methods ; Planarians/*cytology/genetics/metabolism ; Pluripotent Stem Cells/cytology/metabolism ; Regeneration/genetics ; Single-Cell Analysis/*methods ; Transcriptome ; }, abstract = {Flatworms of the species Schmidtea mediterranea are immortal-adult animals contain a large pool of pluripotent stem cells that continuously differentiate into all adult cell types. Therefore, single-cell transcriptome profiling of adult animals should reveal mature and progenitor cells. By combining perturbation experiments, gene expression analysis, a computational method that predicts future cell states from transcriptional changes, and a lineage reconstruction method, we placed all major cell types onto a single lineage tree that connects all cells to a single stem cell compartment. We characterized gene expression changes during differentiation and discovered cell types important for regeneration. Our results demonstrate the importance of single-cell transcriptome analysis for mapping and reconstructing fundamental processes of developmental and regenerative biology at high resolution.}, } @article {pmid29674431, year = {2018}, author = {Fincher, CT and Wurtzel, O and de Hoog, T and Kravarik, KM and Reddien, PW}, title = {Cell type transcriptome atlas for the planarian Schmidtea mediterranea.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {}, doi = {10.1126/science.aaq1736}, pmid = {29674431}, issn = {1095-9203}, support = {R01 GM080639/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Atlases as Topic ; Cell Lineage/genetics ; Cells/*classification/cytology/metabolism ; Gene Expression Profiling/*methods ; Planarians/*cytology ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; Stem Cells/metabolism ; *Transcriptome ; }, abstract = {The transcriptome of a cell dictates its unique cell type biology. We used single-cell RNA sequencing to determine the transcriptomes for essentially every cell type of a complete animal: the regenerative planarian Schmidtea mediterranea. Planarians contain a diverse array of cell types, possess lineage progenitors for differentiated cells (including pluripotent stem cells), and constitutively express positional information, making them ideal for this undertaking. We generated data for 66,783 cells, defining transcriptomes for known and many previously unknown planarian cell types and for putative transition states between stem and differentiated cells. We also uncovered regionally expressed genes in muscle, which harbors positional information. Identifying the transcriptomes for potentially all cell types for many organisms should be readily attainable and represents a powerful approach to metazoan biology.}, } @article {pmid29674430, year = {2018}, author = {Myrow, PM and Lamb, MP and Ewing, RC}, title = {Rapid sea level rise in the aftermath of a Neoproterozoic snowball Earth.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {649-651}, doi = {10.1126/science.aap8612}, pmid = {29674430}, issn = {1095-9203}, abstract = {Earth's most severe climate changes occurred during global-scale "snowball Earth" glaciations, which profoundly altered the planet's atmosphere, oceans, and biosphere. Extreme rates of glacioeustatic sea level rise are predicted by the snowball Earth hypothesis, but supporting geologic evidence has been lacking. We use paleohydraulic analysis of wave ripples and tidal laminae in the Elatina Formation, Australia-deposited after the Marinoan glaciation ~635 million years ago-to show that water depths of 9 to 16 meters remained nearly constant for ~100 years throughout 27 meters of sediment accumulation. This accumulation rate was too great to have been accommodated by subsidence and instead indicates an extraordinarily rapid rate of sea level rise (0.2 to 0.27 meters per year). Our results substantiate a fundamental prediction of snowball Earth models of rapid deglaciation during the early transition to a supergreenhouse climate.}, } @article {pmid29674182, year = {2018}, author = {Shabani, M and Borry, P and Smeers, I and Bekaert, B}, title = {Forensic Epigenetic Age Estimation and Beyond: Ethical and Legal Considerations.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {7}, pages = {489-491}, doi = {10.1016/j.tig.2018.03.006}, pmid = {29674182}, issn = {0168-9525}, abstract = {Forensic geneticists are in a race to develop methods based on DNA methylation for various forensic applications, including age estimation. We argue that using epigenetic biomarkers could reveal a broad range of health and life-style related information, therefore it is necessary to develop adequate safeguards to protect the privacy of the individuals under scrutiny.}, } @article {pmid29673694, year = {2018}, author = {Simo-Droissart, M and Plunkett, GM and Droissart, V and Edwards, MB and Farminhão, JNM and Ječmenica, V and D'haijère, T and Lowry, PP and Sonké, B and Micheneau, C and Carlsward, BS and Azandi, L and Verlynde, S and Hardy, OJ and Martos, F and Bytebier, B and Fischer, E and Stévart, T}, title = {New phylogenetic insights toward developing a natural generic classification of African angraecoid orchids (Vandeae, Orchidaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {241-249}, doi = {10.1016/j.ympev.2018.04.021}, pmid = {29673694}, issn = {1095-9513}, mesh = {Bayes Theorem ; DNA, Plant/genetics ; Indian Ocean ; Orchidaceae/*classification/genetics ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Despite significant progress made in recent years toward developing an infrafamilial classification of Orchidaceae, our understanding of relationships among and within tribal and subtribal groups of epidendroid orchids remains incomplete. To reassess generic delimitation among one group of these epidendroids, the African angraecoids, phylogenetic relationships were inferred from DNA sequence data from three regions, ITS, matK, and the trnL-trnF intergenic spacer, obtained from a broadly representative sample of taxa. Parsimony and Bayesian analyses yielded highly resolved trees that are in clear agreement and show significant support for many key clades within subtribe Angraecinae s.l. Angraecoid orchids comprise two well-supported clades: an African/American group and an Indian Ocean group. Molecular results also support many previously proposed relationships among genera, but also reveal some unexpected relationships. The genera Aerangis, Ancistrorhynchus, Bolusiella, Campylocentrum, Cyrtorchis, Dendrophylax, Eurychone, Microcoelia, Nephrangis, Podangis and Solenangis are all shown to be monophyletic, but Angraecopsis, Diaphananthe and Margelliantha are polyphyletic. Diaphananthe forms three well-supported clades, one of which might represent a new genus, and Rhipidoglossum is paraphyletic with respect to Cribbia and Rhaesteria, and also includes taxa currently assigned to Margelliantha. Tridactyle too is paraphyletic as Eggelingia is embedded within it. The large genus Angraecum is confirmed to be polyphyletic and several groups will have to be recognized as separate genera, including sections Dolabrifolia and Hadrangis. The recently segregated genus Pectinariella (previously recognized as A. sect. Pectinaria) is polyphyletic and its Continental African species will have to be removed. Similarly, some of the species recently transferred to Angraecoides that were previously placed in Angraecum sects. Afrangraecum and Conchoglossum will have to be moved and described as a new genus.}, } @article {pmid29673396, year = {2018}, author = {Denfeld, QE and Habecker, BA and Woodward, WR}, title = {Measurement of plasma norepinephrine and 3,4-dihydroxyphenylglycol: method development for a translational research study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {248}, pmid = {29673396}, issn = {1756-0500}, support = {R01HL093056//National Heart, Lung, and Blood Institute/ ; K12HD043488//Office of Research on Women's Health/ ; R01NR013492//National Institute of Nursing Research/ ; T32HL094294//National Heart, Lung, and Blood Institute/ ; T32 HL094294/HL/NHLBI NIH HHS/United States ; K12 HD043488/HD/NICHD NIH HHS/United States ; R01 NR013492/NR/NINR NIH HHS/United States ; }, mesh = {Chromatography, High Pressure Liquid/*methods ; Electrochemical Techniques/*methods ; Heart Failure/blood ; Humans ; Methoxyhydroxyphenylglycol/*analogs & derivatives/analysis/blood ; Norepinephrine/*analysis/*blood ; Sympathetic Nervous System/*metabolism ; Translational Medical Research/*methods ; }, abstract = {OBJECTIVE: Norepinephrine (NE), a sympathetic neurotransmitter, is often measured in plasma as an index of sympathetic activity. To better understand NE dynamics, it is important to measure its principal metabolite, 3,4-dihydroxyphenylglycol (DHPG), concurrently. Our aim was to present a method, developed in the course of a translational research study, to measure NE and DHPG in human plasma using high performance liquid chromatography with electrochemical detection (HPLC-ED).

RESULTS: After pre-purifying plasma samples by alumina extraction, we used HPLC-ED to separate and quantify NE and DHPG. In order to remove uric acid, which co-eluted with DHPG, a sodium bicarbonate wash was added to the alumina extraction procedure, and we oxidized the column eluates followed by reduction because catechols are reversibly oxidized whereas uric acid is irreversibly oxidized. Average recoveries of plasma NE and DHPG were 35.3 ± 1.0% and 16.3 ± 1.1%, respectively, and there was no detectable uric acid. Our estimated detection limits for NE and DHPG were approximately 85 pg/mL (0.5 pmol/mL) and 165 pg/mL (0.9 pmol/mL), respectively. The measurement of NE and DHPG in human plasma has wide applicability; thus, we describe a method to quantify plasma NE and DHPG in a laboratory setting as a useful tool for translational and clinical research.}, } @article {pmid29673330, year = {2018}, author = {Valdes Franco, JA and Wang, Y and Huo, N and Ponciano, G and Colvin, HA and McMahan, CM and Gu, YQ and Belknap, WR}, title = {Modular assembly of transposable element arrays by microsatellite targeting in the guayule and rice genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {271}, pmid = {29673330}, issn = {1471-2164}, support = {2012-10006//National Institute of Food and Agriculture/ ; }, mesh = {Asteraceae/*genetics ; Base Sequence ; DNA Transposable Elements/*genetics ; Genome, Plant/genetics ; Genomics/*methods ; Microsatellite Repeats/*genetics ; Molecular Sequence Annotation ; Oryza/*genetics ; }, abstract = {BACKGROUND: Guayule (Parthenium argentatum A. Gray) is a rubber-producing desert shrub native to Mexico and the United States. Guayule represents an alternative to Hevea brasiliensis as a source for commercial natural rubber. The efficient application of modern molecular/genetic tools to guayule improvement requires characterization of its genome.

RESULTS: The 1.6 Gb guayule genome was sequenced, assembled and annotated. The final 1.5 Gb assembly, while fragmented (N50 = 22 kb), maps > 95% of the shotgun reads and is essentially complete. Approximately 40,000 transcribed, protein encoding genes were annotated on the assembly. Further characterization of this genome revealed 15 families of small, microsatellite-associated, transposable elements (TEs) with unexpected chromosomal distribution profiles. These SaTar (Satellite Targeted) elements, which are non-autonomous Mu-like elements (MULEs), were frequently observed in multimeric linear arrays of unrelated individual elements within which no individual element is interrupted by another. This uniformly non-nested TE multimer architecture has not been previously described in either eukaryotic or prokaryotic genomes. Five families of similarly distributed non-autonomous MULEs (microsatellite associated, modularly assembled) were characterized in the rice genome. Families of TEs with similar structures and distribution profiles were identified in sorghum and citrus.

CONCLUSION: The sequencing and assembly of the guayule genome provides a foundation for application of current crop improvement technologies to this plant. In addition, characterization of this genome revealed SaTar elements with distribution profiles unique among TEs. Satar targeting appears based on an alternative MULE recombination mechanism with the potential to impact gene evolution.}, } @article {pmid29673327, year = {2018}, author = {Chu, HY and Sprouffske, K and Wagner, A}, title = {Assessing the benefits of horizontal gene transfer by laboratory evolution and genome sequencing.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {54}, pmid = {29673327}, issn = {1471-2148}, support = {739874//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; EpiphysX RTD//SystemsX.ch/International ; }, mesh = {Adaptation, Physiological/genetics ; Base Sequence ; Butyric Acid/metabolism ; *Directed Molecular Evolution ; Escherichia coli/*genetics ; Evolution, Molecular ; Gene Transfer, Horizontal/*genetics ; *Genome, Bacterial ; Mutation/genetics ; Open Reading Frames/genetics ; Operon/genetics ; Phenotype ; Phenylacetates/metabolism ; *Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Recombination is widespread across the tree of life, because it helps purge deleterious mutations and creates novel adaptive traits. In prokaryotes, it often takes the form of horizontal gene transfer from a donor to a recipient bacterium. While such transfer is widespread in natural communities, its immediate fitness benefits are usually unknown. We asked whether any such benefits depend on the environment, and on the identity of donor and recipient strains. To this end, we adapted Escherichia coli to two novel carbon sources over several hundred generations of laboratory evolution, exposing evolving populations to various DNA donors.

RESULTS: At the end of these experiments, we measured fitness and sequenced the genomes of 65 clones from 34 replicate populations to study the genetic changes associated with adaptive evolution. Furthermore, we identified candidate de novo beneficial mutations. During adaptive evolution on the first carbon source, 4-Hydroxyphenylacetic acid (HPA), recombining populations adapted better, which was likely mediated by acquiring the hpa operon from the donor. In contrast, recombining populations did not adapt better to the second carbon source, butyric acid, even though they suffered fewer extinctions than non-recombining populations. The amount of DNA transferred, but not its benefit, strongly depended on the donor-recipient strain combination.

CONCLUSIONS: To our knowledge, our study is the first to investigate the genomic consequences of prokaryotic recombination and horizontal gene transfer during laboratory evolution. It shows that the benefits of recombination strongly depend on the environment and the foreign DNA donor.}, } @article {pmid29673323, year = {2018}, author = {Yang, R and Van Etten, JL and Dehm, SM}, title = {Indel detection from DNA and RNA sequencing data with transIndel.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {270}, pmid = {29673323}, issn = {1471-2164}, support = {R01 CA174777/CA/NCI NIH HHS/United States ; T32 CA009138/CA/NCI NIH HHS/United States ; R01CA17777//National Cancer Institute/ ; }, mesh = {*DNA Mutational Analysis ; Exons/genetics ; Gene Expression Profiling ; Humans ; *INDEL Mutation ; Male ; Neoplasm Metastasis ; Prostatic Neoplasms/genetics/pathology ; RNA Splicing/genetics ; *Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Insertions and deletions (indels) are a major class of genomic variation associated with human disease. Indels are primarily detected from DNA sequencing (DNA-seq) data but their transcriptional consequences remain unexplored due to challenges in discriminating medium-sized and large indels from splicing events in RNA-seq data.

RESULTS: Here, we developed transIndel, a splice-aware algorithm that parses the chimeric alignments predicted by a short read aligner and reconstructs the mid-sized insertions and large deletions based on the linear alignments of split reads from DNA-seq or RNA-seq data. TransIndel exhibits competitive or superior performance over eight state-of-the-art indel detection tools on benchmarks using both synthetic and real DNA-seq data. Additionally, we applied transIndel to DNA-seq and RNA-seq datasets from 333 primary prostate cancer patients from The Cancer Genome Atlas (TCGA) and 59 metastatic prostate cancer patients from AACR-PCF Stand-Up- To-Cancer (SU2C) studies. TransIndel enhanced the taxonomy of DNA- and RNA-level alterations in prostate cancer by identifying recurrent FOXA1 indels as well as exitron splicing in genes implicated in disease progression.

CONCLUSIONS: Our study demonstrates that transIndel is a robust tool for elucidation of medium- and large-sized indels from DNA-seq and RNA-seq data. Including RNA-seq in indel discovery efforts leads to significant improvements in sensitivity for identification of med-sized and large indels missed by DNA-seq, and reveals non-canonical RNA-splicing events in genes associated with disease pathology.}, } @article {pmid29673320, year = {2018}, author = {Liu, N and Liu, J and Li, W and Pan, Q and Liu, J and Yang, X and Yan, J and Xiao, Y}, title = {Intraspecific variation of residual heterozygosity and its utility for quantitative genetic studies in maize.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {66}, pmid = {29673320}, issn = {1471-2229}, support = {2016YFD0100803//the National Key Research and Development Program of China/ ; 31525017, 31401389//the National Natural Science Foundation of China/ ; }, mesh = {Chromosome Mapping ; Chromosomes, Plant/genetics ; Heterozygote ; Quantitative Trait Loci/*genetics ; Zea mays/*genetics ; }, abstract = {BACKGROUND: Residual heterozygosity (RH) in advanced inbred lines of plants benefits quantitative trait locus (QTL) mapping studies. However, knowledge of factors affecting the genome-wide distribution of RH remains limited.

RESULTS: A set of 2196 heterogeneous inbred family (HIF) maize lines derived from 12 recombinant inbred line (RIL) populations was genotyped using the Maize50K SNP chip. A total of 18,615 unique RH intervals were identified, ranging from 505 to 2095 intervals per population, with average maize genome coverage of 94.8%. Across all populations, there were 8.6 RH intervals per HIF line on average, ranging from 1.8 to 14 intervals; the average size of an RH interval was approximately 58.7 Mb, ranging from 7.2 to 74.1 Mb. A given RH region was present in an average of 5 different individuals within a population. Seven RH hotspots, where RH segments were enriched in the genome, were found to be subject to selection during population development. The RH patterns varied significantly across populations, presumably reflecting differences in the genetic background of each population, and 8 QTLs were found to affect heterozygosity levels in the RH hotspots. The potential use of this HIF library for the fine mapping of QTLs was assessed based on publicly available QTL information, achieving a ≤ 1 Mb resolution on average.

CONCLUSION: The examined library of HIF lines offers insight into the RH landscape and its intraspecific variation and provides a useful resource for the QTL cloning of important agronomic traits in maize.}, } @article {pmid29673319, year = {2018}, author = {Aquino-Andrade, A and Merida-Vieyra, J and Arias de la Garza, E and Arzate-Barbosa, P and De Colsa Ranero, A}, title = {Carbapenemase-producing Enterobacteriaceae in Mexico: report of seven non-clonal cases in a pediatric hospital.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {38}, pmid = {29673319}, issn = {1471-2180}, abstract = {BACKGROUND: Carbapenemases-producing Enterobacteriaceae (CPE) are a worldwide public health emergency. In Mexico, reports of CPE are limited, particularly in the pediatric population. Here, we describe the clinical, epidemiological, and molecular characteristics of seven consecutive cases in a third-level pediatric hospital in Mexico City over a four-month period during 2016.

RESULTS: The Enterobacteriaceae identified were three Escherichia coli strains (producing OXA-232, NDM-1 and KPC-2), two Klebsiella pneumoniae strains (producing KPC-2 and NDM-1), one Klebsiella oxytoca strain producing OXA-48 and one Enterobacter cloacae strain producing NDM-1. The majority of patients had underlying disesases, three were immunocompromised, and three had infections involved the skin and soft tissues. Half patients died as a result of CPE infection.

CONCLUSIONS: This study represents the first report of E. coli ST131-O25b clone producing NDM-1 in Latin America. In addition, this study is the first finding of K. oxytoca producing OXA-48 and E. coli producing OXA-232 in Mexican pediatric patients.}, } @article {pmid29673318, year = {2018}, author = {He, Y and Ahmad, D and Zhang, X and Zhang, Y and Wu, L and Jiang, P and Ma, H}, title = {Genome-wide analysis of family-1 UDP glycosyltransferases (UGT) and identification of UGT genes for FHB resistance in wheat (Triticum aestivum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {67}, pmid = {29673318}, issn = {1471-2229}, support = {EU678781//European Union Horizon 2020 Mycokey project/ ; 2016YFD0100500, 2016YFE0112900//National key project for the research and development of China/ ; CARS-03//China agricultural research system program/ ; 31561143004//National Natural Science Foundation of China/ ; BK20170605//Natural science foundation of Jiangsu province, China/ ; }, mesh = {Fusarium/*pathogenicity ; Gene Expression Regulation, Plant/genetics/physiology ; Glucuronosyltransferase/genetics/*metabolism ; Glycosyltransferases/genetics/*metabolism ; Phylogeny ; Plant Diseases/*microbiology ; Plant Proteins/genetics/*metabolism ; Triticum/genetics/metabolism/*microbiology ; }, abstract = {BACKGROUND: Fusarium head blight (FHB), a devastating disease in wheat worldwide, results in yield loses and mycotoxin, such as deoxynivalenol (DON), accumulation in infected grains. DON also facilitates the pathogen colonization and spread of FHB symptoms during disease development. UDP-glycosyltransferase enzymes (UGTs) are known to contribute to detoxification and enhance FHB resistance by glycosylating DON into DON-3-glucoside (D3G) in wheat. However, a comprehensive investigation of wheat (Triticum aestivum) UGT genes is still lacking.

RESULTS: In this study, we carried out a genome-wide analysis of family-1 UDP glycosyltransferases in wheat based on the PSPG conserved box that resulted in the identification of 179 putative UGT genes. The identified genes were clustered into 16 major phylogenetic groups with a lack of phylogenetic group K. The UGT genes were invariably distributed among all the chromosomes of the 3 genomes. At least 10 intron insertion events were found in the UGT sequences, where intron 4 was observed as the most conserved intron. The expression analysis of the wheat UGT genes using both online microarray data and quantitative real-time PCR verification suggested the distinct role of UGT genes in different tissues and developmental stages. The expression of many UGT genes was up-regulated after Fusarium graminearum inoculation, and six of the genes were further verified by RT-qPCR.

CONCLUSION: We identified 179 UGT genes from wheat using the available sequenced wheat genome. This study provides useful insight into the phylogenetic structure, distribution, and expression patterns of family-1 UDP glycosyltransferases in wheat. The results also offer a foundation for future work aimed at elucidating the molecular mechanisms underlying the resistance to FHB and DON accumulation.}, } @article {pmid29673316, year = {2018}, author = {Li, Z and Wang, Y and Wang, F}, title = {A study on fast calling variants from next-generation sequencing data using decision tree.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {145}, pmid = {29673316}, issn = {1471-2105}, support = {61472086//National Natural Science Foundation of China/International ; 31501067//National Natural Science Foundation of China/International ; 2016YFC0902100//National Key Research and Development Program of China/International ; }, mesh = {Algorithms ; Asian Continental Ancestry Group/genetics ; *Decision Trees ; Exome/genetics ; *Genetic Variation ; Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; INDEL Mutation/genetics ; Polymorphism, Single Nucleotide/genetics ; Software ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: The rapid development of next-generation sequencing (NGS) technology has continuously been refreshing the throughput of sequencing data. However, due to the lack of a smart tool that is both fast and accurate, the analysis task for NGS data, especially those with low-coverage, remains challenging.

RESULTS: We proposed a decision-tree based variant calling algorithm. Experiments on a set of real data indicate that our algorithm achieves high accuracy and sensitivity for SNVs and indels and shows good adaptability on low-coverage data. In particular, our algorithm is obviously faster than 3 widely used tools in our experiments.

CONCLUSIONS: We implemented our algorithm in a software named Fuwa and applied it together with 4 well-known variant callers, i.e., Platypus, GATK-UnifiedGenotyper, GATK-HaplotypeCaller and SAMtools, to three sequencing data sets of a well-studied sample NA12878, which were produced by whole-genome, whole-exome and low-coverage whole-genome sequencing technology respectively. We also conducted additional experiments on the WGS data of 4 newly released samples that have not been used to populate dbSNP.}, } @article {pmid29673315, year = {2018}, author = {King, R and Brown, NA and Urban, M and Hammond-Kosack, KE}, title = {Inter-genome comparison of the Quorn fungus Fusarium venenatum and the closely related plant infecting pathogen Fusarium graminearum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {269}, pmid = {29673315}, issn = {1471-2164}, support = {BBS/E/C/000I0250//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J00426X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J/004383/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/1000488/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/K020056/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N011686/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Fusarium/*genetics/*physiology ; Genome, Fungal/genetics ; *Genomics ; Lycopersicon esculentum/*microbiology ; Molecular Sequence Annotation ; Triticum/*microbiology ; }, abstract = {BACKGROUND: The soil dwelling saprotrophic non-pathogenic fungus Fusarium venenatum, routinely used in the commercial fermentation industry, is phylogenetically closely related to the globally important cereal and non-cereal infecting pathogen F. graminearum. This study aimed to sequence, assemble and annotate the F. venenatum (strain A3/5) genome, and compare this genome with F. graminearum.

RESULTS: Using shotgun sequencing, a 38,660,329 bp F. venenatum genome was assembled into four chromosomes, and a 78,618 bp mitochondrial genome. In comparison to F. graminearum, the predicted gene count of 13,946 was slightly lower. The F. venenatum centromeres were found to be 25% smaller compared to F. graminearum. Chromosome length was 2.8% greater in F. venenatum, primarily due to an increased abundance of repetitive elements and transposons, but not transposon diversity. On chromosome 3 a major sequence rearrangement was found, but its overall gene content was relatively unchanged. Unlike homothallic F. graminearum, heterothallic F. venenatum possessed the MAT1-1 type locus, but lacked the MAT1-2 locus. The F. venenatum genome has the type A trichothecene mycotoxin TRI5 cluster, whereas F. graminearum has type B. From the F. venenatum gene set, 786 predicted proteins were species-specific versus NCBI. The annotated F. venenatum genome was predicted to possess more genes coding for hydrolytic enzymes and species-specific genes involved in the breakdown of polysaccharides than F. graminearum. Comparison of the two genomes reduced the previously defined F. graminearum-specific gene set from 741 to 692 genes. A comparison of the F. graminearum versus F. venenatum proteomes identified 15 putative secondary metabolite gene clusters (SMC), 109 secreted proteins and 38 candidate effectors not found in F. venenatum. Five of the 15 F. graminearum-specific SMCs that were either absent or highly divergent in the F. venenatum genome showed increased in planta expression. In addition, two predicted F. graminearum transcription factors previously shown to be required for fungal virulence on wheat plants were absent or exhibited high sequence divergence.

CONCLUSIONS: This study identifies differences between the F. venenatum and F. graminearum genomes that may contribute to contrasting lifestyles, and highlights the repertoire of F. graminearum-specific candidate genes and SMCs potentially required for pathogenesis.}, } @article {pmid29673314, year = {2018}, author = {Bertl, J and Guo, Q and Juul, M and Besenbacher, S and Nielsen, MM and Hornshøj, H and Pedersen, JS and Hobolth, A}, title = {A site specific model and analysis of the neutral somatic mutation rate in whole-genome cancer data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {147}, pmid = {29673314}, issn = {1471-2105}, mesh = {Databases, Genetic ; Epigenomics ; *Genome, Human ; Humans ; *Models, Genetic ; Mutation/*genetics ; *Mutation Rate ; Neoplasms/*genetics ; Polymorphism, Single Nucleotide/genetics ; Regression Analysis ; }, abstract = {BACKGROUND: Detailed modelling of the neutral mutational process in cancer cells is crucial for identifying driver mutations and understanding the mutational mechanisms that act during cancer development. The neutral mutational process is very complex: whole-genome analyses have revealed that the mutation rate differs between cancer types, between patients and along the genome depending on the genetic and epigenetic context. Therefore, methods that predict the number of different types of mutations in regions or specific genomic elements must consider local genomic explanatory variables. A major drawback of most methods is the need to average the explanatory variables across the entire region or genomic element. This procedure is particularly problematic if the explanatory variable varies dramatically in the element under consideration.

RESULTS: To take into account the fine scale of the explanatory variables, we model the probabilities of different types of mutations for each position in the genome by multinomial logistic regression. We analyse 505 cancer genomes from 14 different cancer types and compare the performance in predicting mutation rate for both regional based models and site-specific models. We show that for 1000 randomly selected genomic positions, the site-specific model predicts the mutation rate much better than regional based models. We use a forward selection procedure to identify the most important explanatory variables. The procedure identifies site-specific conservation (phyloP), replication timing, and expression level as the best predictors for the mutation rate. Finally, our model confirms and quantifies certain well-known mutational signatures.

CONCLUSION: We find that our site-specific multinomial regression model outperforms the regional based models. The possibility of including genomic variables on different scales and patient specific variables makes it a versatile framework for studying different mutational mechanisms. Our model can serve as the neutral null model for the mutational process; regions that deviate from the null model are candidates for elements that drive cancer development.}, } @article {pmid29673313, year = {2018}, author = {Delicado, D and Hauffe, T and Wilke, T}, title = {Ecological opportunity may facilitate diversification in Palearctic freshwater organisms: a case study on hydrobiid gastropods.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {55}, pmid = {29673313}, issn = {1471-2148}, support = {TC01226371//Justus Liebig Universität Gießen/International ; }, mesh = {Animals ; Aquatic Organisms/*genetics ; Bayes Theorem ; *Biodiversity ; *Ecosystem ; *Fresh Water ; Gastropoda/*genetics ; Genetic Speciation ; Models, Biological ; Phylogeny ; Temperature ; }, abstract = {BACKGROUND: Differences in species richness among phylogenetic clades are attributed to clade age and/or variation in diversification rates. Access to ecological opportunity may trigger a temporary increase in diversification rates and ecomorphological variation. In addition, lower body temperatures in poikilothermic animals may result in decreasing speciation rates as proposed by the metabolic theory of ecology. For strictly freshwater organisms, environmental gradients within a river continuum, linked to elevation and temperature, might promote access to ecological opportunity and alter metabolic rates, eventually influencing speciation and extinction processes. To test these hypotheses, we investigated the influence of environmental temperature and elevation, as proxies for body temperature and ecological opportunity, respectively, on speciation rates and ecomorphological divergence. As model systems served two closely related gastropod genera with unequal species richness and habitat preferences - Pseudamnicola and Corrosella.

RESULTS: Lineage-through-time plots and Bayesian macroevolutionary modeling evidenced that Pseudamnicola species, which typically live in lower reaches of rivers, displayed significantly elevated speciation rates in comparison to the 'headwater genus' Corrosella. Moreover, state-dependent speciation models suggested that the speciation rate increased with decreasing elevation, supporting the ecological opportunity hypothesis. In contrast, a significant effect of environmental temperature, as proposed by the metabolic theory of ecology, could not be observed. Disparity-through-time plots, models of ecomorphological evolution, and ancestral habitat estimation showed for Pseudamnicola species rapid morphological divergence shortly after periods of elevational and habitat divergence. In contrast, Corrosella species did not deviate from null models of drift-like evolution.

CONCLUSION: Our finding that speciation rates are correlated with elevation and ecomorphological disparity but not with environmental temperatures suggests that differences in ecological opportunity may have played a key role in Corrosella and Pseudamnicola diversifications. We propose that Pseudamnicola lineages experienced higher ecological opportunity through dispersal to new locations or habitats in lowlands, which may explain the increase in speciation rates and morphological change. In contrast, the evolution of Corrosella in headwaters is likely less facilitated by the environment and more by non-ecological processes.}, } @article {pmid29673312, year = {2018}, author = {Chen, N and He, S and Geng, J and Song, ZJ and Han, PH and Qin, J and Zhao, Z and Song, YC and Wang, HX and Dang, CX}, title = {Overexpression of Contactin 1 promotes growth, migration and invasion in Hs578T breast cancer cells.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {5}, pmid = {29673312}, issn = {1471-2121}, mesh = {Animals ; Breast Neoplasms/*pathology ; Cell Line, Tumor ; *Cell Movement ; Cell Proliferation ; Contactin 1/*metabolism ; Female ; Humans ; Male ; Mice, Nude ; Neoplasm Invasiveness ; Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Contactin1 (CNTN1) has been shown to play an important role in the invasion and metastasis of several tumors; however, the role of CNTN1 in breast cancer has not been fully studied. The purpose of this study is to investigate the role of CNTN1 in regulating tumor growth, migration and invasion in breast cancer.

RESULTS: To investigate its function, CNTN1 was expressed in Hs578T cells. CNTN1 expression was confirmed by western blot, immunohistochemistry and real-time RT-PCR. The effect of CNTN1 overexpression on proliferation, migration and invasion of Hs578T breast cancer cells was assessed in vitro and in vivo. Our results showed that CNTN1 overexpression promoted Hs578T cell proliferation, cell cycle progression, colony formation, invasion and migration. Notably, overexpression of CNTN1 in Hs578T cells enhanced the growth of mouse xenograft tumors.

CONCLUSIONS: CNTN1 promotes growth, metastasis and invasion of Hs578T breast cancer cell line. Thus, therapies targeting CNTN1 may prove efficacious for breast cancer. However, further investigation is required to understand the mechanism by which CNTN1 influences proliferation, metastasis and invasion in breast cancer.}, } @article {pmid29673311, year = {2018}, author = {Mao, W and Wang, T and Zhang, W and Gong, H}, title = {Identification of residue pairing in interacting β-strands from a predicted residue contact map.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {146}, pmid = {29673311}, issn = {1471-2105}, support = {31670723//National Natural Science Foundation of China (CN)/International ; 31621092//National Natural Science Foundation of China (CN)/International ; }, mesh = {Algorithms ; Amino Acids/*chemistry ; Computational Biology/*methods ; Models, Molecular ; Protein Conformation, beta-Strand ; Protein Structure, Tertiary ; Proteins/*chemistry ; Reproducibility of Results ; }, abstract = {BACKGROUND: Despite the rapid progress of protein residue contact prediction, predicted residue contact maps frequently contain many errors. However, information of residue pairing in β strands could be extracted from a noisy contact map, due to the presence of characteristic contact patterns in β-β interactions. This information may benefit the tertiary structure prediction of mainly β proteins. In this work, we propose a novel ridge-detection-based β-β contact predictor to identify residue pairing in β strands from any predicted residue contact map.

RESULTS: Our algorithm RDb2C adopts ridge detection, a well-developed technique in computer image processing, to capture consecutive residue contacts, and then utilizes a novel multi-stage random forest framework to integrate the ridge information and additional features for prediction. Starting from the predicted contact map of CCMpred, RDb2C remarkably outperforms all state-of-the-art methods on two conventional test sets of β proteins (BetaSheet916 and BetaSheet1452), and achieves F1-scores of ~ 62% and ~ 76% at the residue level and strand level, respectively. Taking the prediction of the more advanced RaptorX-Contact as input, RDb2C achieves impressively higher performance, with F1-scores reaching ~ 76% and ~ 86% at the residue level and strand level, respectively. In a test of structural modeling using the top 1 L predicted contacts as constraints, for 61 mainly β proteins, the average TM-score achieves 0.442 when using the raw RaptorX-Contact prediction, but increases to 0.506 when using the improved prediction by RDb2C.

CONCLUSION: Our method can significantly improve the prediction of β-β contacts from any predicted residue contact maps. Prediction results of our algorithm could be directly applied to effectively facilitate the practical structure prediction of mainly β proteins.

AVAILABILITY: All source data and codes are available at http://166.111.152.91/Downloads.html or the GitHub address of https://github.com/wzmao/RDb2C .}, } @article {pmid29673310, year = {2018}, author = {Nguyen, HN and Paveau, V and Cauchois, C and Kervrann, C}, title = {ATMAD: robust image analysis for Automatic Tissue MicroArray De-arraying.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {148}, pmid = {29673310}, issn = {1471-2105}, mesh = {Algorithms ; Automation ; Computer Simulation ; Databases, Genetic ; Humans ; *Image Processing, Computer-Assisted ; Microscopy, Fluorescence ; Oligonucleotide Array Sequence Analysis/*methods ; *Software ; Tissue Array Analysis/*methods ; Workflow ; }, abstract = {BACKGROUND: Over the last two decades, an innovative technology called Tissue Microarray (TMA), which combines multi-tissue and DNA microarray concepts, has been widely used in the field of histology. It consists of a collection of several (up to 1000 or more) tissue samples that are assembled onto a single support - typically a glass slide - according to a design grid (array) layout, in order to allow multiplex analysis by treating numerous samples under identical and standardized conditions. However, during the TMA manufacturing process, the sample positions can be highly distorted from the design grid due to the imprecision when assembling tissue samples and the deformation of the embedding waxes. Consequently, these distortions may lead to severe errors of (histological) assay results when the sample identities are mismatched between the design and its manufactured output. The development of a robust method for de-arraying TMA, which localizes and matches TMA samples with their design grid, is therefore crucial to overcome the bottleneck of this prominent technology.

RESULTS: In this paper, we propose an Automatic, fast and robust TMA De-arraying (ATMAD) approach dedicated to images acquired with brightfield and fluorescence microscopes (or scanners). First, tissue samples are localized in the large image by applying a locally adaptive thresholding on the isotropic wavelet transform of the input TMA image. To reduce false detections, a parametric shape model is considered for segmenting ellipse-shaped objects at each detected position. Segmented objects that do not meet the size and the roundness criteria are discarded from the list of tissue samples before being matched with the design grid. Sample matching is performed by estimating the TMA grid deformation under the thin-plate model. Finally, thanks to the estimated deformation, the true tissue samples that were preliminary rejected in the early image processing step are recognized by running a second segmentation step.

CONCLUSIONS: We developed a novel de-arraying approach for TMA analysis. By combining wavelet-based detection, active contour segmentation, and thin-plate spline interpolation, our approach is able to handle TMA images with high dynamic, poor signal-to-noise ratio, complex background and non-linear deformation of TMA grid. In addition, the deformation estimation produces quantitative information to asset the manufacturing quality of TMAs.}, } @article {pmid29672994, year = {2018}, author = {Wang, MZ and Bu, XQ and Li, L and Dong, BC and Li, HL and Yu, FH}, title = {Constraints on the evolution of phenotypic plasticity in the clonal plant Hydrocotyle vulgaris.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {1006-1017}, doi = {10.1111/jeb.13281}, pmid = {29672994}, issn = {1420-9101}, abstract = {The evolution of phenotypic plasticity of plant traits may be constrained by costs and limits. However, the precise constraints are still unclear for many traits under different ecological contexts. In a glasshouse experiment, we grew ramets of 12 genotypes of a clonal plant Hydrocotyle vulgaris under the control (full light and no flood), shade and flood conditions and tested the potential costs and limits of plasticity in 13 morphological and physiological traits in response to light availability and flood variation. In particular, we used multiple regression and correlation analyses to evaluate potential plasticity costs, developmental instability costs and developmental range limits of each trait. We detected significant costs of plasticity in specific petiole length and specific leaf area in response to shade under the full light condition and developmental range limits in specific internode length and intercellular CO2 concentration in response to light availability variation. However, we did not observe significant costs or limits of plasticity in any of the 13 traits in response to flood variation. Our results suggest that the evolution of phenotypic plasticity in plant traits can be constrained by costs and limits, but such constraints may be infrequent and differ under different environmental contexts.}, } @article {pmid29672987, year = {2018}, author = {Luijckx, P and Ho, EKH and Stanić, A and Agrawal, AF}, title = {Mutation accumulation in populations of varying size: large effect mutations cause most mutational decline in the rotifer Brachionus calyciflorus under UV-C radiation.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {924-932}, doi = {10.1111/jeb.13282}, pmid = {29672987}, issn = {1420-9101}, abstract = {Theory predicts that fitness decline via mutation accumulation will depend on population size, but there are only a few direct tests of this key idea. To gain a qualitative understanding of the fitness effect of new mutations, we performed a mutation accumulation experiment with the facultative sexual rotifer Brachionus calyciflorus at six different population sizes under UV-C radiation. Lifetime reproduction assays conducted after ten and sixteen UV-C radiations showed that while small populations lost fitness, fitness losses diminished rapidly with increasing population size. Populations kept as low as 10 individuals were able to maintain fitness close to the nonmutagenized populations throughout the experiment indicating that selection was able to remove the majority of large effect mutations in small populations. Although our results also seem to imply that small populations are effectively immune to mutational decay, we caution against this interpretation. Given sufficient time, populations of moderate to large size can experience declines in fitness from accumulating weakly deleterious mutations as demonstrated by fitness estimates from simulations and, tentatively, from a long-term experiment with populations of moderate size. There is mounting evidence to suggest that mutational distributions contain a heavier tail of large effects. Our results suggest that this is also true when the mutational spectrum is altered by UV radiation.}, } @article {pmid29672982, year = {2018}, author = {Esin, EV and Markevich, GN and Pichugin, MY}, title = {Juvenile divergence in adaptive traits among seven sympatric fish ecomorphs arises before moving to different lacustrine habitats.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {1018-1034}, doi = {10.1111/jeb.13283}, pmid = {29672982}, issn = {1420-9101}, abstract = {Identifying the mechanisms initiating sympatric diversification in vertebrates has remained a conceptual challenge. Here, we analyse an assemblage of sympatric charr (Salvelinus malma) morphs from landlocked Lake Kronotskoe basin as a model to uncover the divergence pathways in freshwater fishes during the early life history stages. All morphs have distinct developmental biology, but a similar developmental rate retardation compared to the ancestor. Our study reveals that adult morphological differences, which acquire functionality at maturation, originate in the early juvenile stages due to heterochrony in skeletogenesis and allometric changes triggered by variation in metabolic activity. The craniofacial differences among the morphs result from asynchronous development of several skeletal modules. The accelerated ossification of teeth-armed bones occurs in predatory feeding morphs, whereas cranial cover ossification is promoted in benthivorous morphs. These contrasting growth patterns have led to seven phenotypes that span a range far beyond the ancestral variability. The most distinct morphs are a riverine spawning, epilimnetic predator and a lacustrine spawning, profundal benthic feeder. Taken together, we argue that the adaptive morphological differentiation in these sympatric freshwater fishes is driven by diverging patterns in ossification rate and metabolic activity against a background of uneven somatic growth. This divergence is primarily associated with basic environmental differences on the nursery grounds that might be unrelated to resource use. This nonheritable phenotype divergence is then exposed to natural selection that could result in further adaptive genetic changes.}, } @article {pmid29672765, year = {2018}, author = {Wheatley, RM and Poole, PS}, title = {Mechanisms of bacterial attachment to roots.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {448-461}, doi = {10.1093/femsre/fuy014}, pmid = {29672765}, issn = {1574-6976}, mesh = {Bacteria/*genetics/*metabolism ; Host-Pathogen Interactions/physiology ; Plant Roots/*microbiology ; Plants/*microbiology ; Species Specificity ; }, abstract = {The attachment of bacteria to roots constitutes the first physical step in many plant-microbe interactions. These interactions exert both positive and negative influences on agricultural systems depending on whether a growth-promoting, symbiotic or pathogenic relationship transpires. A common biphasic mechanism of root attachment exists across agriculturally important microbial species, including Rhizobium, Agrobacterium, Pseudomonas, Azospirillum and Salmonella. Attachment studies have revealed how plant-microbe interactions develop, and how to manipulate these relationships for agricultural benefit. Here, we review our current understanding of the molecular mechanisms governing plant-microbe root attachment and draw together a common biphasic model.}, } @article {pmid29672732, year = {2018}, author = {Hilgers, L and Hartmann, S and Hofreiter, M and von Rintelen, T}, title = {Novel Genes, Ancient Genes, and Gene Co-Option Contributed to the Genetic Basis of the Radula, a Molluscan Innovation.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1638-1652}, pmid = {29672732}, issn = {1537-1719}, abstract = {The radula is the central foraging organ and apomorphy of the Mollusca. However, in contrast to other innovations, including the mollusk shell, genetic underpinnings of radula formation remain virtually unknown. Here, we present the first radula formative tissue transcriptome using the viviparous freshwater snail Tylomelania sarasinorum and compare it to foot tissue and the shell-building mantle of the same species. We combine differential expression, functional enrichment, and phylostratigraphic analyses to identify both specific and shared genetic underpinnings of the three tissues as well as their dominant functions and evolutionary origins. Gene expression of radula formative tissue is very distinct, but nevertheless more similar to mantle than to foot. Generally, the genetic bases of both radula and shell formation were shaped by novel orchestration of preexisting genes and continuous evolution of novel genes. A significantly increased proportion of radula-specific genes originated since the origin of stem-mollusks, indicating that novel genes were especially important for radula evolution. Genes with radula-specific expression in our study are frequently also expressed during the formation of other lophotrochozoan hard structures, like chaetae (hes1, arx), spicules (gbx), and shells of mollusks (gbx, heph) and brachiopods (heph), suggesting gene co-option for hard structure formation. Finally, a Lophotrochozoa-specific chitin synthase with a myosin motor domain (CS-MD), which is expressed during mollusk and brachiopod shell formation, had radula-specific expression in our study. CS-MD potentially facilitated the construction of complex chitinous structures and points at the potential of molecular novelties to promote the evolution of different morphological innovations.}, } @article {pmid29672704, year = {2018}, author = {Probst, AJ and Banfield, JF}, title = {Homologous Recombination and Transposon Propagation Shape the Population Structure of an Organism from the Deep Subsurface with Minimal Metabolism.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1115-1119}, pmid = {29672704}, issn = {1759-6653}, mesh = {Archaea/genetics/metabolism ; Bacteria/genetics/metabolism ; DNA Transposable Elements/*genetics ; Genetics, Population ; Genome, Archaeal/*genetics ; Homologous Recombination/*genetics ; Metagenomics ; }, abstract = {DPANN archaea are primarily known based on genomes from metagenomes and single cells. We reconstructed a complete population genome for Candidatus "Forterrea," a Diapherotrite with a predicted symbiotic lifestyle probably centered around nucleotide metabolism and RuBisCO. Genome-wide analysis of sequence variation provided insights into the processes that shape its population structure in the deep subsurface. The genome contains many transposons, yet reconstruction of a complete genome from a short-read insert data set was possible because most occurred only in some individuals. Accuracy of the final reconstruction could be verified because the genome displays the pattern of cumulative GC skew known for some archaea but more typically associated with bacteria. Sequence variation is highly localized, and most pronounced around transposons and relatively close to the origin of replication. Patterns of variation are best explained by homologous recombination, a process previously not described for DPANN archaea.}, } @article {pmid29672703, year = {2018}, author = {Keshri, V and Panda, A and Levasseur, A and Rolain, JM and Pontarotti, P and Raoult, D}, title = {Phylogenomic Analysis of β-Lactamase in Archaea and Bacteria Enables the Identification of Putative New Members.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1106-1114}, pmid = {29672703}, issn = {1759-6653}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Archaea/enzymology ; Bacteria/enzymology ; Carbapenems/*biosynthesis/chemistry ; Humans ; Metagenomics ; *Phylogeny ; beta-Lactamases/*genetics ; beta-Lactams/*metabolism ; }, abstract = {β-lactamases are enzymes which are commonly produced by bacteria and which degrade the β-lactam ring of β-lactam antibiotics, namely penicillins, cephalosporins, carbapenems, and monobactams, and inactivate these antibiotics. We performed a rational and comprehensive investigation of β-lactamases in different biological databases. In this study, we constructed hidden Markov model profiles as well as the ancestral sequence of four classes of β-lactamases (A, B, C, and D), which were used to identify potential β-lactamases from environmental metagenomic (1206), human microbiome metagenomic (6417), human microbiome reference genome (1310), and NCBI's nonredundant databases (44101). Our analysis revealed the existence of putative β-lactamases in the metagenomic databases, which appeared to be similar to the four different molecular classes (A-D). This is the first report on the large-scale phylogenetic diversity of new members of β-lactamases, and our results revealed that metagenomic database dark-matter contains β-lactamase-like antibiotic resistance genes.}, } @article {pmid29672280, year = {2018}, author = {Pengra, IGG and Marchaterre, MA and Bass, AH}, title = {FoxP2 Expression in a Highly Vocal Teleost Fish with Comparisons to Tetrapods.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {2}, pages = {82-96}, doi = {10.1159/000487793}, pmid = {29672280}, issn = {1421-9743}, abstract = {Motivated by studies of speech deficits in humans, several studies over the past two decades have investigated the potential role of a forkhead domain transcription factor, FoxP2, in the central control of acoustic signaling/vocalization among vertebrates. Comparative neuroanatomical studies that mainly include mammalian and avian species have mapped the distribution of FoxP2 expression in multiple brain regions that imply a greater functional significance beyond vocalization that might be shared broadly across vertebrate lineages. To date, reports for teleost fish have been limited in number and scope to nonvocal species. Here, we map the neuroanatomical distribution of FoxP2 mRNA expression in a highly vocal teleost, the plainfin midshipman (Porichthys notatus). We report an extensive overlap between FoxP2 expression and vocal, auditory, and steroid-signaling systems with robust expression at multiple sites in the telencephalon, the preoptic area, the diencephalon, and the midbrain. Label was far more restricted in the hindbrain though robust in one region of the reticular formation. A comparison with other teleosts and tetrapods suggests an evolutionarily conserved FoxP2 phenotype important to vocal-acoustic and, more broadly, sensorimotor function among vertebrates.}, } @article {pmid29671943, year = {2018}, author = {Bronte, G and Bravaccini, S and Bronte, E and Burgio, MA and Rolfo, C and Delmonte, A and Crinò, L}, title = {Epithelial-to-mesenchymal transition in the context of epidermal growth factor receptor inhibition in non-small-cell lung cancer.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1735-1746}, doi = {10.1111/brv.12416}, pmid = {29671943}, issn = {1469-185X}, abstract = {The identification of oncogenic driver mutations in non-small-cell lung cancer (NSCLC) has led to the development of targeted drugs. Tyrosine kinase inhibitors (TKIs) directed against the epidermal growth factor receptor (EGFR) target lung tumours bearing EGFR-activating mutations. This new therapeutic strategy has greatly improved tumour response rates. However, drug resistance invariably occurs during TKI-based treatment. Epithelial-to-mesenchymal transition (EMT) is one of the resistance mechanisms identified in EGFR-mutated NSCLC treated with TKIs. In this review we gather together the most important findings on this phenomenon in relation to cancer stem cells and cancer epigenetics. We also outline the correlation between the effects of stromal factors from the microenvironment, the transcription factors activated, the epigenetic changes in chromatin, and the evolution of cellular behaviour. Notably, EMT has already been shown to be the link between benign lung diseases such as chronic obstructive pulmonary disease and lung carcinogenesis. The various mechanisms of acquired resistance to EGFR-TKIs are also briefly described to provide background information on EMT. Our extensive review of the scientific literature serves to highlight the cellular and molecular events that lead to the onset of EMT in NSCLC cells treated with EGFR-TKIs. Finally, we put forward a hypothesis to explain why, in some cases, EMT rather than other known mechanisms is involved in resistance to TKIs.}, } @article {pmid29671720, year = {2018}, author = {Tsuboi, K and Sakai, HD and Nur, N and Stedman, KM and Kurosawa, N and Suwanto, A}, title = {Sulfurisphaera javensis sp. nov., a hyperthermophilic and acidophilic archaeon isolated from Indonesian hot spring, and reclassification of Sulfolobus tokodaii Suzuki et al. 2002 as Sulfurisphaera tokodaii comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1907-1913}, doi = {10.1099/ijsem.0.002765}, pmid = {29671720}, issn = {1466-5034}, mesh = {Base Composition ; Chemoautotrophic Growth ; DNA, Archaeal/genetics ; Hot Springs/*microbiology ; Indonesia ; Lipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfolobaceae/*classification/genetics/isolation & purification ; Sulfolobus ; }, abstract = {A novel hyperthermophilic, acidophilic and facultatively anaerobic archaeon, strain KD-1T, was isolated from an acidic hot spring in Indonesia and characterized with the phylogenetically related species Sulfurisphaera ohwakuensis Kurosawa et al. 1998, Sulfolobus tokodaii Suzuki et al., 2002 and Sulfolobus yangmingensis Jan et al. 1999. Cells of KD-1T were irregular cocci with diameters of 0.9-1.3 µm. The strain grew at 60-90 °C (optimum 80-85 °C), pH 2.5-6.0 (optimum pH 3.5-4.0) and 0-1.0 % (w/v) NaCl concentration. KD-1T grew anaerobically in the presence of S0 (headspace: H2/CO2) and FeCl3 (headspace: N2). Under aerobic conditions, chemolithoautotrophic growth occurred on S0, pyrite, K2S4O6, Na2S2O3 and H2. This strain utilized various complex substrates, such as yeast extract, but did not grow on sugars and amino acids as the sole carbon source. The main core lipids were calditoglycerocaldarchaeol and caldarchaeol. The DNA G+C content was 30.6 mol%. Analyses of phylogenetic trees based on 16S rRNA and 23S rRNA genes indicated that KD-1T formed an independent lineage near Sulfurisphaera ohwakuensis TA-1T, Sulfolobus tokodaii 7T and Sulfolobus yangmingensis YM1T. On the basis of the results of morphological, physiological, chemotaxonomic and phylogenetic analyses, KD-1T represents a novel species of the genus Sulfurisphaera Kurosawa et al. 1998, for which the name Sulfurisphaera javensis sp. nov. is proposed. The type strain is KD-1T (=JCM 32117T=InaCC Ar81T). Based on the data, we also propose the reclassification of Sulfolobus tokodaii Suzuki et al., 2002 as Sulfurisphaera tokodaii comb. nov. (type strain 7T=JCM 10545T=DSM 16993T).}, } @article {pmid29671405, year = {2018}, author = {Mori, T and Ngouv, H and Hayashida, M and Akutsu, T and Nacher, JC}, title = {ncRNA-disease association prediction based on sequence information and tripartite network.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {37}, pmid = {29671405}, issn = {1752-0509}, abstract = {BACKGROUND: Current technology has demonstrated that mutation and deregulation of non-coding RNAs (ncRNAs) are associated with diverse human diseases and important biological processes. Therefore, developing a novel computational method for predicting potential ncRNA-disease associations could benefit pathologists in understanding the correlation between ncRNAs and disease diagnosis, treatment, and prevention. However, only a few studies have investigated these associations in pathogenesis.

RESULTS: This study utilizes a disease-target-ncRNA tripartite network, and computes prediction scores between each disease-ncRNA pair by integrating biological information derived from pairwise similarity based upon sequence expressions with weights obtained from a multi-layer resource allocation technique. Our proposed algorithm was evaluated based on a 5-fold-cross-validation with optimal kernel parameter tuning. In addition, we achieved an average AUC that varies from 0.75 without link cut to 0.57 with link cut methods, which outperforms a previous method using the same evaluation methodology. Furthermore, the algorithm predicted 23 ncRNA-disease associations supported by other independent biological experimental studies.

CONCLUSIONS: Taken together, these results demonstrate the capability and accuracy of predicting further biological significant associations between ncRNAs and diseases and highlight the importance of adding biological sequence information to enhance predictions.}, } @article {pmid29671404, year = {2018}, author = {Buiga, P and Elson, A and Tabernero, L and Schwartz, JM}, title = {Regulation of dual specificity phosphatases in breast cancer during initial treatment with Herceptin: a Boolean model analysis.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {11}, pmid = {29671404}, issn = {1752-0509}, abstract = {BACKGROUND: 25% of breast cancer patients suffer from aggressive HER2-positive tumours that are characterised by overexpression of the HER2 protein or by its increased tyrosine kinase activity. Herceptin is a major drug used to treat HER2 positive breast cancer. Understanding the molecular events that occur when breast cancer cells are exposed to Herceptin is therefore of significant importance. Dual specificity phosphatases (DUSPs) are central regulators of cell signalling that function downstream of HER2, but their role in the cellular response to Herceptin is mostly unknown. This study aims to model the initial effects of Herceptin exposure on DUSPs in HER2-positive breast cancer cells using Boolean modelling.

RESULTS: We experimentally measured expression time courses of 21 different DUSPs between 0 and 24 h following Herceptin treatment of human MDA-MB-453 HER2-positive breast cancer cells. We clustered these time courses into patterns of similar dynamics over time. In parallel, we built a series of Boolean models representing the known regulatory mechanisms of DUSPs and then demonstrated that the dynamics predicted by the models is in agreement with the experimental data. Furthermore, we used the models to predict regulatory mechanisms of DUSPs, where these mechanisms were partially known.

CONCLUSIONS: Boolean modelling is a powerful technique to investigate and understand signalling pathways. We obtained an understanding of different regulatory pathways in breast cancer and new insights on how these signalling pathways are activated. This method can be generalized to other drugs and longer time courses to better understand how resistance to drugs develops in cancer cells over time.}, } @article {pmid29671403, year = {2018}, author = {Lyu, M and Chen, J and Jiang, Y and Dong, W and Fang, Z and Li, S}, title = {KDiamend: a package for detecting key drivers in a molecular ecological network of disease.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {5}, pmid = {29671403}, issn = {1752-0509}, abstract = {BACKGROUND: Microbial abundance profiles are applied widely to understand diseases from the aspect of microbial communities. By investigating the abundance associations of species or genes, we can construct molecular ecological networks (MENs). The MENs are often constructed by calculating the Pearson correlation coefficient (PCC) between genes. In this work, we also applied multimodal mutual information (MMI) to construct MENs. The members which drive the concerned MENs are referred to as key drivers.

RESULTS: We proposed a novel method to detect the key drivers. First, we partitioned the MEN into subnetworks. Then we identified the most pertinent subnetworks to the disease by measuring the correlation between the abundance pattern and the delegated phenotype-the variable representing the disease phenotypes. Last, for each identified subnetwork, we detected the key driver by PageRank. We developed a package named KDiamend and applied it to the gut and oral microbial data to detect key drivers for Type 2 diabetes (T2D) and Rheumatoid Arthritis (RA). We detected six T2D-relevant subnetworks and three key drivers of them are related to the carbohydrate metabolic process. In addition, we detected nine subnetworks related to RA, a disease caused by compromised immune systems. The extracted subnetworks include InterPro matches (IPRs) concerned with immunoglobulin, Sporulation, biofilm, Flaviviruses, bacteriophage, etc., while the development of biofilms is regarded as one of the drivers of persistent infections.

CONCLUSION: KDiamend is feasible to detect key drivers and offers insights to uncover the development of diseases. The package is freely available at http://www.deepomics.org/pipelines/3DCD6955FEF2E64A/ .}, } @article {pmid29671402, year = {2018}, author = {Yim, S and Yu, H and Jang, D and Lee, D}, title = {Annotating activation/inhibition relationships to protein-protein interactions using gene ontology relations.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {9}, pmid = {29671402}, issn = {1752-0509}, abstract = {BACKGROUND: Signaling pathways can be reconstructed by identifying 'effect types' (i.e. activation/inhibition) of protein-protein interactions (PPIs). Effect types are composed of 'directions' (i.e. upstream/downstream) and 'signs' (i.e. positive/negative), thereby requiring directions as well as signs of PPIs to predict signaling events from PPI networks. Here, we propose a computational method for systemically annotating effect types to PPIs using relations between functional information of proteins.

RESULTS: We used regulates, positively regulates, and negatively regulates relations in Gene Ontology (GO) to predict directions and signs of PPIs. These relations indicate both directions and signs between GO terms so that we can project directions and signs between relevant GO terms to PPIs. Independent test results showed that our method is effective for predicting both directions and signs of PPIs. Moreover, our method outperformed a previous GO-based method that did not consider the relations between GO terms. We annotated effect types to human PPIs and validated several highly confident effect types against literature. The annotated human PPIs are available in Additional file 2 to aid signaling pathway reconstruction and network biology research.

CONCLUSIONS: We annotated effect types to PPIs by using regulates, positively regulates, and negatively regulates relations in GO. We demonstrated that those relations are effective for predicting not only signs, but also directions of PPIs. The usefulness of those relations suggests their potential applications to other types of interactions such as protein-DNA interactions.}, } @article {pmid29671401, year = {2018}, author = {Zhang, S}, title = {Comparisons of gene coexpression network modules in breast cancer and ovarian cancer.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {8}, pmid = {29671401}, issn = {1752-0509}, abstract = {BACKGROUND: Breast cancer and ovarian cancer are hormone driven and are known to have some predisposition genes in common such as the two well known cancer genes BRCA1 and BRCA2. The objective of this study is to compare the coexpression network modules of both cancers, so as to infer the potential cancer-related modules.

METHODS: We applied the eigen-decomposition to the matrix that integrates the gene coexpression networks of both breast cancer and ovarian cancer. With hierarchical clustering of the related eigenvectors, we obtained the network modules of both cancers simultaneously. Enrichment analysis on Gene Ontology (GO), KEGG pathway, Disease Ontology (DO), and Gene Set Enrichment Analysis (GSEA) in the identified modules was performed.

RESULTS: We identified 43 modules that are enriched by at least one of the four types of enrichments. 31, 25, and 18 modules are enriched by GO terms, KEGG pathways, and DO terms, respectively. The structure of 29 modules in both cancers is significantly different with p-values less than 0.05, of which 25 modules have larger densities in ovarian cancer. One module was found to be significantly enriched by the terms related to breast cancer from GO, KEGG and DO enrichment. One module was found to be significantly enriched by ovarian cancer related terms.

CONCLUSION: Breast cancer and ovarian cancer share some common properties on the module level. Integration of both cancers helps identifying the potential cancer associated modules.}, } @article {pmid29671400, year = {2018}, author = {Peng, J and Hui, W and Shang, X}, title = {Measuring phenotype-phenotype similarity through the interactome.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {114}, pmid = {29671400}, issn = {1471-2105}, abstract = {BACKGROUND: Recently, measuring phenotype similarity began to play an important role in disease diagnosis. Researchers have begun to pay attention to develop phenotype similarity measurement. However, existing methods ignore the interactions between phenotype-associated proteins, which may lead to inaccurate phenotype similarity.

RESULTS: We proposed a network-based method PhenoNet to calculate the similarity between phenotypes. We localized phenotypes in the network and calculated the similarity between phenotype-associated modules by modeling both the inter- and intra-similarity.

CONCLUSIONS: PhenoNet was evaluated on two independent evaluation datasets: gene ontology and gene expression data. The result shows that PhenoNet performs better than the state-of-art methods on all evaluation tests.}, } @article {pmid29671399, year = {2018}, author = {Tou, H and Yao, L and Wei, Z and Zhuang, X and Zhang, B}, title = {Automatic infection detection based on electronic medical records.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {117}, pmid = {29671399}, issn = {1471-2105}, abstract = {BACKGROUND: Making accurate patient care decision, as early as possible, is a constant challenge, especially for physicians in the emergency department. The increasing volumes of electronic medical records (EMRs) open new horizons for automatic diagnosis. In this paper, we propose to use machine learning approaches for automatic infection detection based on EMRs. Five categories of information are utilized for prediction, including personal information, admission note, vital signs, diagnose test results and medical image diagnose.

RESULTS: Experimental results on a newly constructed EMRs dataset from emergency department show that machine learning models can achieve a decent performance for infection detection with area under the receiver operator characteristic curve (AUC) of 0.88. Out of all the five types of information, admission note in text form makes the most contribution with the AUC of 0.87.

CONCLUSIONS: This study provides a state-of-the-art EMRs processing system to automatically make medical decisions. It extracts five types of features associated with infection and achieves a decent performance on automatic infection detection based on machine learning models.}, } @article {pmid29671398, year = {2018}, author = {Hu, Y and Zhao, T and Zhang, N and Zang, T and Zhang, J and Cheng, L}, title = {Identifying diseases-related metabolites using random walk.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {116}, pmid = {29671398}, issn = {1471-2105}, abstract = {BACKGROUND: Metabolites disrupted by abnormal state of human body are deemed as the effect of diseases. In comparison with the cause of diseases like genes, these markers are easier to be captured for the prevention and diagnosis of metabolic diseases. Currently, a large number of metabolic markers of diseases need to be explored, which drive us to do this work.

METHODS: The existing metabolite-disease associations were extracted from Human Metabolome Database (HMDB) using a text mining tool NCBO annotator as priori knowledge. Next we calculated the similarity of a pair-wise metabolites based on the similarity of disease sets of them. Then, all the similarities of metabolite pairs were utilized for constructing a weighted metabolite association network (WMAN). Subsequently, the network was utilized for predicting novel metabolic markers of diseases using random walk.

RESULTS: Totally, 604 metabolites and 228 diseases were extracted from HMDB. From 604 metabolites, 453 metabolites are selected to construct the WMAN, where each metabolite is deemed as a node, and the similarity of two metabolites as the weight of the edge linking them. The performance of the network is validated using the leave one out method. As a result, the high area under the receiver operating characteristic curve (AUC) (0.7048) is achieved. The further case studies for identifying novel metabolites of diabetes mellitus were validated in the recent studies.

CONCLUSION: In this paper, we presented a novel method for prioritizing metabolite-disease pairs. The superior performance validates its reliability for exploring novel metabolic markers of diseases.}, } @article {pmid29671397, year = {2018}, author = {Wang, Z and Wu, X and Wang, Y}, title = {A framework for analyzing DNA methylation data from Illumina Infinium HumanMethylation450 BeadChip.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {115}, pmid = {29671397}, issn = {1471-2105}, abstract = {BACKGROUND: DNA methylation has been identified to be widely associated to complex diseases. Among biological platforms to profile DNA methylation in human, the Illumina Infinium HumanMethylation450 BeadChip (450K) has been accepted as one of the most efficient technologies. However, challenges exist in analysis of DNA methylation data generated by this technology due to widespread biases.

RESULTS: Here we proposed a generalized framework for evaluating data analysis methods for Illumina 450K array. This framework considers the following steps towards a successful analysis: importing data, quality control, within-array normalization, correcting type bias, detecting differentially methylated probes or regions and biological interpretation.

CONCLUSIONS: We evaluated five methods using three real datasets, and proposed outperform methods for the Illumina 450K array data analysis. Minfi and methylumi are optimal choice when analyzing small dataset. BMIQ and RCP are proper to correcting type bias and the normalized result of them can be used to discover DMPs. R package missMethyl is suitable for GO term enrichment analysis and biological interpretation.}, } @article {pmid29671396, year = {2018}, author = {Ranjan, B and Chong, KH and Zheng, J}, title = {Composite mathematical modeling of calcium signaling behind neuronal cell death in Alzheimer's disease.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {10}, pmid = {29671396}, issn = {1752-0509}, abstract = {BACKGROUND: Alzheimer's disease (AD) is a progressive neurological disorder, recognized as the most common cause of dementia affecting people aged 65 and above. AD is characterized by an increase in amyloid metabolism, and by the misfolding and deposition of β-amyloid oligomers in and around neurons in the brain. These processes remodel the calcium signaling mechanism in neurons, leading to cell death via apoptosis. Despite accumulating knowledge about the biological processes underlying AD, mathematical models to date are restricted to depicting only a small portion of the pathology.

RESULTS: Here, we integrated multiple mathematical models to analyze and understand the relationship among amyloid depositions, calcium signaling and mitochondrial permeability transition pore (PTP) related cell apoptosis in AD. The model was used to simulate calcium dynamics in the absence and presence of AD. In the absence of AD, i.e. without β-amyloid deposition, mitochondrial and cytosolic calcium level remains in the low resting concentration. However, our in silico simulation of the presence of AD with the β-amyloid deposition, shows an increase in the entry of calcium ions into the cell and dysregulation of Ca 2+ channel receptors on the Endoplasmic Reticulum. This composite model enabled us to make simulation that is not possible to measure experimentally.

CONCLUSIONS: Our mathematical model depicting the mechanisms affecting calcium signaling in neurons can help understand AD at the systems level and has potential for diagnostic and therapeutic applications.}, } @article {pmid29671395, year = {2018}, author = {Qiu, Y and Jiang, H and Ching, WK and Cheng, X}, title = {Discovery of Boolean metabolic networks: integer linear programming based approach.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {7}, pmid = {29671395}, issn = {1752-0509}, abstract = {BACKGROUND: Traditional drug discovery methods focused on the efficacy of drugs rather than their toxicity. However, toxicity and/or lack of efficacy are produced when unintended targets are affected in metabolic networks. Thus, identification of biological targets which can be manipulated to produce the desired effect with minimum side-effects has become an important and challenging topic. Efficient computational methods are required to identify the drug targets while incurring minimal side-effects.

RESULTS: In this paper, we propose a graph-based computational damage model that summarizes the impact of enzymes on compounds in metabolic networks. An efficient method based on Integer Linear Programming formalism is then developed to identify the optimal enzyme-combination so as to minimize the side-effects. The identified target enzymes for known successful drugs are then verified by comparing the results with those in the existing literature.

CONCLUSIONS: Side-effects reduction plays a crucial role in the study of drug development. A graph-based computational damage model is proposed and the theoretical analysis states the captured problem is NP-completeness. The proposed approaches can therefore contribute to the discovery of drug targets. Our developed software is available at " http://hkumath.hku.hk/~wkc/APBC2018-metabolic-network.zip ".}, } @article {pmid29671394, year = {2018}, author = {Sun, S and Sun, X and Zheng, Y}, title = {Higher-order partial least squares for predicting gene expression levels from chromatin states.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {113}, pmid = {29671394}, issn = {1471-2105}, abstract = {BACKGROUND: Extensive studies have shown that gene expression levels are strongly affected by chromatin mark combinations via at least two mechanisms, i.e., activation or repression. But their combinatorial patterns are still unclear. To further understand the relationship between histone modifications and gene expression levels, here in this paper, we introduce a purely geometric higher-order representation, tensor (also called multidimensional array), which might borrow more unknown interactions in chromatin states to predicting gene expression levels.

RESULTS: The prediction models were learned from regions around upstream 10k base pairs and downstream 10k base pairs of the transcriptional start sites (TSSs) on three species (i.e., Human, Rhesus Macaque, and Chimpanzee) with five histone modifications (i.e., H3K4me1, H3K4me3, H3K27ac, H3K27me3, and Pol II). Experimental results demonstrate that the proposed method is more powerful to predicting gene expression levels than several other popular methods. Specifically, our method enable to get more powerful performance on both commonly used criteria, R and RMSE, as high as 1.7% and 11%, respectively.

CONCLUSIONS: The overall aim of this work is to show that the higher-order representation is able to include more unknown interaction information between histone modifications across different species.}, } @article {pmid29671393, year = {2018}, author = {Yu, H and Mao, KT and Shi, JY and Huang, H and Chen, Z and Dong, K and Yiu, SM}, title = {Predicting and understanding comprehensive drug-drug interactions via semi-nonnegative matrix factorization.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {14}, pmid = {29671393}, issn = {1752-0509}, abstract = {BACKGROUND: Drug-drug interactions (DDIs) always cause unexpected and even adverse drug reactions. It is important to identify DDIs before drugs are used in the market. However, preclinical identification of DDIs requires much money and time. Computational approaches have exhibited their abilities to predict potential DDIs on a large scale by utilizing pre-market drug properties (e.g. chemical structure). Nevertheless, none of them can predict two comprehensive types of DDIs, including enhancive and degressive DDIs, which increases and decreases the behaviors of the interacting drugs respectively. There is a lack of systematic analysis on the structural relationship among known DDIs. Revealing such a relationship is very important, because it is able to help understand how DDIs occur. Both the prediction of comprehensive DDIs and the discovery of structural relationship among them play an important guidance when making a co-prescription.

RESULTS: In this work, treating a set of comprehensive DDIs as a signed network, we design a novel model (DDINMF) for the prediction of enhancive and degressive DDIs based on semi-nonnegative matrix factorization. Inspiringly, DDINMF achieves the conventional DDI prediction (AUROC = 0.872 and AUPR = 0.605) and the comprehensive DDI prediction (AUROC = 0.796 and AUPR = 0.579). Compared with two state-of-the-art approaches, DDINMF shows it superiority. Finally, representing DDIs as a binary network and a signed network respectively, an analysis based on NMF reveals crucial knowledge hidden among DDIs.

CONCLUSIONS: Our approach is able to predict not only conventional binary DDIs but also comprehensive DDIs. More importantly, it reveals several key points about the DDI network: (1) both binary and signed networks show fairly clear clusters, in which both drug degree and the difference between positive degree and negative degree show significant distribution; (2) the drugs having large degrees tend to have a larger difference between positive degree and negative degree; (3) though the binary DDI network contains no information about enhancive and degressive DDIs at all, it implies some of their relationship in the comprehensive DDI matrix; (4) the occurrence of signs indicating enhancive and degressive DDIs is not random because the comprehensive DDI network is equipped with a structural balance.}, } @article {pmid29671392, year = {2018}, author = {Mukherjee, K and Hasan, MM and Boucher, C and Kahveci, T}, title = {Counting motifs in dynamic networks.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {6}, pmid = {29671392}, issn = {1752-0509}, abstract = {BACKGROUND: A network motif is a sub-network that occurs frequently in a given network. Detection of such motifs is important since they uncover functions and local properties of the given biological network. Finding motifs is however a computationally challenging task as it requires solving the costly subgraph isomorphism problem. Moreover, the topology of biological networks change over time. These changing networks are called dynamic biological networks. As the network evolves, frequency of each motif in the network also changes. Computing the frequency of a given motif from scratch in a dynamic network as the network topology evolves is infeasible, particularly for large and fast evolving networks.

RESULTS: In this article, we design and develop a scalable method for counting the number of motifs in a dynamic biological network. Our method incrementally updates the frequency of each motif as the underlying network's topology evolves. Our experiments demonstrate that our method can update the frequency of each motif in orders of magnitude faster than counting the motif embeddings every time the network changes. If the network evolves more frequently, the margin with which our method outperforms the existing static methods, increases.

CONCLUSIONS: We evaluated our method extensively using synthetic and real datasets, and show that our method is highly accurate(≥ 96%) and that it can be scaled to large dense networks. The results on real data demonstrate the utility of our method in revealing interesting insights on the evolution of biological processes.}, } @article {pmid29671391, year = {2018}, author = {Hao, X and Hao, J and Wang, L and Hou, H}, title = {Effective norm emergence in cell systems under limited communication.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {119}, pmid = {29671391}, issn = {1471-2105}, abstract = {BACKGROUND: The cooperation of cells in biological systems is similar to that of agents in cooperative multi-agent systems. Research findings in multi-agent systems literature can provide valuable inspirations to biological research. The well-coordinated states in cell systems can be viewed as desirable social norms in cooperative multi-agent systems. One important research question is how a norm can rapidly emerge with limited communication resources.

RESULTS: In this work, we propose a learning approach which can trade off the agents' performance of coordinating on a consistent norm and the communication cost involved. During the learning process, the agents can dynamically adjust their coordination set according to their own observations and pick out the most crucial agents to coordinate with. In this way, our method significantly reduces the coordination dependence among agents.

CONCLUSION: The experiment results show that our method can efficiently facilitate the social norm emergence among agents, and also scale well to large-scale populations.}, } @article {pmid29671390, year = {2018}, author = {Guo, Y and Liu, S and Li, Z and Shang, X}, title = {BCDForest: a boosting cascade deep forest model towards the classification of cancer subtypes based on gene expression data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {118}, pmid = {29671390}, issn = {1471-2105}, abstract = {BACKGROUND: The classification of cancer subtypes is of great importance to cancer disease diagnosis and therapy. Many supervised learning approaches have been applied to cancer subtype classification in the past few years, especially of deep learning based approaches. Recently, the deep forest model has been proposed as an alternative of deep neural networks to learn hyper-representations by using cascade ensemble decision trees. It has been proved that the deep forest model has competitive or even better performance than deep neural networks in some extent. However, the standard deep forest model may face overfitting and ensemble diversity challenges when dealing with small sample size and high-dimensional biology data.

RESULTS: In this paper, we propose a deep learning model, so-called BCDForest, to address cancer subtype classification on small-scale biology datasets, which can be viewed as a modification of the standard deep forest model. The BCDForest distinguishes from the standard deep forest model with the following two main contributions: First, a named multi-class-grained scanning method is proposed to train multiple binary classifiers to encourage diversity of ensemble. Meanwhile, the fitting quality of each classifier is considered in representation learning. Second, we propose a boosting strategy to emphasize more important features in cascade forests, thus to propagate the benefits of discriminative features among cascade layers to improve the classification performance. Systematic comparison experiments on both microarray and RNA-Seq gene expression datasets demonstrate that our method consistently outperforms the state-of-the-art methods in application of cancer subtype classification.

CONCLUSIONS: The multi-class-grained scanning and boosting strategy in our model provide an effective solution to ease the overfitting challenge and improve the robustness of deep forest model working on small-scale data. Our model provides a useful approach to the classification of cancer subtypes by using deep learning on high-dimensional and small-scale biology data.}, } @article {pmid29671389, year = {2018}, author = {Chu, Y and Teng, M and Wang, Y}, title = {Modeling and correct the GC bias of tumor and normal WGS data for SCNA based tumor subclonal population inferring.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 5}, pages = {112}, pmid = {29671389}, issn = {1471-2105}, abstract = {BACKGROUND: Somatic copy number alternations (SCNAs) can be utilized to infer tumor subclonal populations in whole genome seuqncing studies, where usually their read count ratios between tumor-normal paired samples serve as the inferring proxy. Existing SCNA based subclonal population inferring tools consider the GC bias of tumor and normal sample is of the same fature, and could be fully offset by read count ratio. However, we found that, the read count ratio on SCNA segments presents a Log linear biased pattern, which influence existing read count ratios based subclonal inferring tools performance. Currently no correction tools take into account the read ratio bias.

RESULTS: We present Pre-SCNAClonal, a tool that improving tumor subclonal population inferring by correcting GC-bias at SCNAs level. Pre-SCNAClonal first corrects GC bias using Markov chain Monte Carlo probability model, then accurately locates baseline DNA segments (not containing any SCNAs) with a hierarchy clustering model. We show Pre-SCNAClonal's superiority to exsiting GC-bias correction methods at any level of subclonal population.

CONCLUSIONS: Pre-SCNAClonal could be run independently as well as serving as pre-processing/gc-correction step in conjuntion with exsiting SCNA-based subclonal inferring tools.}, } @article {pmid29671388, year = {2018}, author = {Teraguchi, S and Kumagai, Y}, title = {Estimation of diffusion constants from single molecular measurement without explicit tracking.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 1}, pages = {15}, pmid = {29671388}, issn = {1752-0509}, abstract = {BACKGROUND: Time course measurement of single molecules on a cell surface provides detailed information about the dynamics of the molecules that would otherwise be inaccessible. To extract the quantitative information, single particle tracking (SPT) is typically performed. However, trajectories extracted by SPT inevitably have linking errors when the diffusion speed of single molecules is high compared to the scale of the particle density.

METHODS: To circumvent this problem, we develop an algorithm to estimate diffusion constants without relying on SPT. The proposed algorithm is based on a probabilistic model of the distance to the nearest point in subsequent frames. This probabilistic model generalizes the model of single particle Brownian motion under an isolated environment into the one surrounded by indistinguishable multiple particles, with a mean field approximation.

RESULTS: We demonstrate that the proposed algorithm provides reasonable estimation of diffusion constants, even when other methods suffer due to high particle density or inhomogeneous particle distribution. In addition, our algorithm can be used for visualization of time course data from single molecular measurements.

CONCLUSIONS: The proposed algorithm based on the probabilistic model of indistinguishable Brownian particles provide accurate estimation of diffusion constants even in the regime where the traditional SPT methods underestimate them due to linking errors.}, } @article {pmid29670290, year = {2018}, author = {Lemoine, F and Domelevo Entfellner, JB and Wilkinson, E and Correia, D and Dávila Felipe, M and De Oliveira, T and Gascuel, O}, title = {Renewing Felsenstein's phylogenetic bootstrap in the era of big data.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {452-456}, pmid = {29670290}, issn = {1476-4687}, support = {U24 HG006941/HG/NHGRI NIH HHS/United States ; U41 HG006941/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Computer Simulation ; DNA Barcoding, Taxonomic ; *Data Interpretation, Statistical ; *Datasets as Topic ; HIV-1/*genetics ; Haplorhini/genetics ; Mammals/*genetics ; *Phylogeny ; pol Gene Products, Human Immunodeficiency Virus/chemistry/genetics ; }, abstract = {Felsenstein's application of the bootstrap method to evolutionary trees is one of the most cited scientific papers of all time. The bootstrap method, which is based on resampling and replications, is used extensively to assess the robustness of phylogenetic inferences. However, increasing numbers of sequences are now available for a wide variety of species, and phylogenies based on hundreds or thousands of taxa are becoming routine. With phylogenies of this size Felsenstein's bootstrap tends to yield very low supports, especially on deep branches. Here we propose a new version of the phylogenetic bootstrap in which the presence of inferred branches in replications is measured using a gradual 'transfer' distance rather than the binary presence or absence index used in Felsenstein's original version. The resulting supports are higher and do not induce falsely supported branches. The application of our method to large mammal, HIV and simulated datasets reveals their phylogenetic signals, whereas Felsenstein's bootstrap fails to do so.}, } @article {pmid29670289, year = {2018}, author = {Coquel, F and Silva, MJ and Técher, H and Zadorozhny, K and Sharma, S and Nieminuszczy, J and Mettling, C and Dardillac, E and Barthe, A and Schmitz, AL and Promonet, A and Cribier, A and Sarrazin, A and Niedzwiedz, W and Lopez, B and Costanzo, V and Krejci, L and Chabes, A and Benkirane, M and Lin, YL and Pasero, P}, title = {SAMHD1 acts at stalled replication forks to prevent interferon induction.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {57-61}, doi = {10.1038/s41586-018-0050-1}, pmid = {29670289}, issn = {1476-4687}, mesh = {Checkpoint Kinase 1/metabolism ; Cytosol/metabolism ; *DNA Replication ; DNA, Single-Stranded/metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Inflammation/immunology/metabolism/prevention & control ; Interferon Type I/immunology/*metabolism ; MRE11 Homologue Protein/metabolism ; Membrane Proteins/metabolism ; Nucleotidyltransferases/metabolism ; RecQ Helicases/metabolism ; SAM Domain and HD Domain-Containing Protein 1/deficiency/*metabolism ; }, abstract = {SAMHD1 was previously characterized as a dNTPase that protects cells from viral infections. Mutations in SAMHD1 are implicated in cancer development and in a severe congenital inflammatory disease known as Aicardi-Goutières syndrome. The mechanism by which SAMHD1 protects against cancer and chronic inflammation is unknown. Here we show that SAMHD1 promotes degradation of nascent DNA at stalled replication forks in human cell lines by stimulating the exonuclease activity of MRE11. This function activates the ATR-CHK1 checkpoint and allows the forks to restart replication. In SAMHD1-depleted cells, single-stranded DNA fragments are released from stalled forks and accumulate in the cytosol, where they activate the cGAS-STING pathway to induce expression of pro-inflammatory type I interferons. SAMHD1 is thus an important player in the replication stress response, which prevents chronic inflammation by limiting the release of single-stranded DNA from stalled replication forks.}, } @article {pmid29670288, year = {2018}, author = {Yang, Z and Han, S and Keller, M and Kaiser, A and Bender, BJ and Bosse, M and Burkert, K and Kögler, LM and Wifling, D and Bernhardt, G and Plank, N and Littmann, T and Schmidt, P and Yi, C and Li, B and Ye, S and Zhang, R and Xu, B and Larhammar, D and Stevens, RC and Huster, D and Meiler, J and Zhao, Q and Beck-Sickinger, AG and Buschauer, A and Wu, B}, title = {Structural basis of ligand binding modes at the neuropeptide Y Y1 receptor.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {520-524}, pmid = {29670288}, issn = {1476-4687}, support = {R01 DK097376/DK/NIDDK NIH HHS/United States ; R01 GM080403/GM/NIGMS NIH HHS/United States ; R01 HL122010/HL/NHLBI NIH HHS/United States ; T32 GM007628/GM/NIGMS NIH HHS/United States ; }, mesh = {Arginine/*analogs & derivatives/chemistry/metabolism/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Dihydropyridines/*chemistry/*metabolism/pharmacology ; Diphenylacetic Acids/*chemistry/*metabolism/pharmacology ; Humans ; Inositol Phosphates/metabolism ; Ligands ; Molecular Docking Simulation ; Mutant Proteins/chemistry/metabolism ; Mutation ; Neuropeptide Y/chemistry/*metabolism/pharmacology ; Nuclear Magnetic Resonance, Biomolecular ; Phenylurea Compounds/*chemistry/*metabolism/pharmacology ; Protein Binding ; Receptors, Neuropeptide Y/agonists/*antagonists & inhibitors/*chemistry/metabolism ; Structure-Activity Relationship ; Substrate Specificity ; }, abstract = {Neuropeptide Y (NPY) receptors belong to the G-protein-coupled receptor superfamily and have important roles in food intake, anxiety and cancer biology 1,2 . The NPY-Y receptor system has emerged as one of the most complex networks with three peptide ligands (NPY, peptide YY and pancreatic polypeptide) binding to four receptors in most mammals, namely the Y1, Y2, Y4 and Y5 receptors, with different affinity and selectivity 3 . NPY is the most powerful stimulant of food intake and this effect is primarily mediated by the Y1 receptor (Y1R) 4 . A number of peptides and small-molecule compounds have been characterized as Y1R antagonists and have shown clinical potential in the treatment of obesity 4 , tumour 1 and bone loss 5 . However, their clinical usage has been hampered by low potency and selectivity, poor brain penetration ability or lack of oral bioavailability 6 . Here we report crystal structures of the human Y1R bound to the two selective antagonists UR-MK299 and BMS-193885 at 2.7 and 3.0 Å resolution, respectively. The structures combined with mutagenesis studies reveal the binding modes of Y1R to several structurally diverse antagonists and the determinants of ligand selectivity. The Y1R structure and molecular docking of the endogenous agonist NPY, together with nuclear magnetic resonance, photo-crosslinking and functional studies, provide insights into the binding behaviour of the agonist and for the first time, to our knowledge, determine the interaction of its N terminus with the receptor. These insights into Y1R can enable structure-based drug discovery that targets NPY receptors.}, } @article {pmid29670287, year = {2018}, author = {Bambouskova, M and Gorvel, L and Lampropoulou, V and Sergushichev, A and Loginicheva, E and Johnson, K and Korenfeld, D and Mathyer, ME and Kim, H and Huang, LH and Duncan, D and Bregman, H and Keskin, A and Santeford, A and Apte, RS and Sehgal, R and Johnson, B and Amarasinghe, GK and Soares, MP and Satoh, T and Akira, S and Hai, T and de Guzman Strong, C and Auclair, K and Roddy, TP and Biller, SA and Jovanovic, M and Klechevsky, E and Stewart, KM and Randolph, GJ and Artyomov, MN}, title = {Electrophilic properties of itaconate and derivatives regulate the IκBζ-ATF3 inflammatory axis.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {501-504}, pmid = {29670287}, issn = {1476-4687}, support = {R01 AI125618/AI/NIAID NIH HHS/United States ; }, mesh = {Activating Transcription Factor 3/*metabolism ; Animals ; Cells, Cultured ; Cytokines/immunology/metabolism ; Female ; Gene Expression Regulation/drug effects ; Glutathione/metabolism ; Humans ; I-kappa B Proteins/*metabolism ; Inflammation/drug therapy/metabolism ; Interleukin-6/metabolism ; Keratinocytes/drug effects/metabolism ; Macrophages/drug effects/metabolism ; Mice ; Mice, Inbred C57BL ; NF-E2-Related Factor 2/metabolism ; Psoriasis/drug therapy/pathology ; Stress, Physiological/drug effects ; Succinates/administration & dosage/chemistry/*metabolism/pharmacology/therapeutic use ; Toll-Like Receptors/immunology ; }, abstract = {Metabolic regulation has been recognized as a powerful principle guiding immune responses. Inflammatory macrophages undergo extensive metabolic rewiring 1 marked by the production of substantial amounts of itaconate, which has recently been described as an immunoregulatory metabolite 2 . Itaconate and its membrane-permeable derivative dimethyl itaconate (DI) selectively inhibit a subset of cytokines 2 , including IL-6 and IL-12 but not TNF. The major effects of itaconate on cellular metabolism during macrophage activation have been attributed to the inhibition of succinate dehydrogenase2,3, yet this inhibition alone is not sufficient to account for the pronounced immunoregulatory effects observed in the case of DI. Furthermore, the regulatory pathway responsible for such selective effects of itaconate and DI on the inflammatory program has not been defined. Here we show that itaconate and DI induce electrophilic stress, react with glutathione and subsequently induce both Nrf2 (also known as NFE2L2)-dependent and -independent responses. We find that electrophilic stress can selectively regulate secondary, but not primary, transcriptional responses to toll-like receptor stimulation via inhibition of IκBζ protein induction. The regulation of IκBζ is independent of Nrf2, and we identify ATF3 as its key mediator. The inhibitory effect is conserved across species and cell types, and the in vivo administration of DI can ameliorate IL-17-IκBζ-driven skin pathology in a mouse model of psoriasis, highlighting the therapeutic potential of this regulatory pathway. Our results demonstrate that targeting the DI-IκBζ regulatory axis could be an important new strategy for the treatment of IL-17-IκBζ-mediated autoimmune diseases.}, } @article {pmid29670286, year = {2018}, author = {Kim, HS and Tan, Y and Ma, W and Merkurjev, D and Destici, E and Ma, Q and Suter, T and Ohgi, K and Friedman, M and Skowronska-Krawczyk, D and Rosenfeld, MG}, title = {Pluripotency factors functionally premark cell-type-restricted enhancers in ES cells.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {510-514}, pmid = {29670286}, issn = {1476-4687}, support = {R37 DK039949/DK/NIDDK NIH HHS/United States ; R01 AG057706/AG/NIA NIH HHS/United States ; R01 GM104459/GM/NIGMS NIH HHS/United States ; R01 CA213371/CA/NCI NIH HHS/United States ; R01 CA097134/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 DK018477/DK/NIDDK NIH HHS/United States ; R01 DK039949/DK/NIDDK NIH HHS/United States ; R01 NS093066/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*genetics ; *Enhancer Elements, Genetic ; Epigenesis, Genetic ; Female ; Gene Expression Regulation/*genetics ; Macrophages/cytology/metabolism ; Mice ; Mouse Embryonic Stem Cells/*cytology/*metabolism ; Neural Stem Cells/cytology/metabolism ; Organ Specificity ; Pluripotent Stem Cells/cytology/*metabolism ; Reproducibility of Results ; Transcription Factors/*metabolism ; }, abstract = {Enhancers for embryonic stem (ES) cell-expressed genes and lineage-determining factors are characterized by conventional marks of enhancer activation in ES cells1-3, but it remains unclear whether enhancers destined to regulate cell-type-restricted transcription units might also have distinct signatures in ES cells. Here we show that cell-type-restricted enhancers are 'premarked' and activated as transcription units by the binding of one or two ES cell transcription factors, although they do not exhibit traditional enhancer epigenetic marks in ES cells, thus uncovering the initial temporal origins of cell-type-restricted enhancers. This premarking is required for future cell-type-restricted enhancer activity in the differentiated cells, with the strength of the ES cell signature being functionally important for the subsequent robustness of cell-type-restricted enhancer activation. We have experimentally validated this model in macrophage-restricted enhancers and neural precursor cell (NPC)-restricted enhancers using ES cell-derived macrophages or NPCs, edited to contain specific ES cell transcription factor motif deletions. DNA hydroxyl-methylation of enhancers in ES cells, determined by ES cell transcription factors, may serve as a potential molecular memory for subsequent enhancer activation in mature macrophages. These findings suggest that the massive repertoire of cell-type-restricted enhancers are essentially hierarchically and obligatorily premarked by binding of a defining ES cell transcription factor in ES cells, dictating the robustness of enhancer activation in mature cells.}, } @article {pmid29670285, year = {2018}, author = {Nasralla, D and Coussios, CC and Mergental, H and Akhtar, MZ and Butler, AJ and Ceresa, CDL and Chiocchia, V and Dutton, SJ and García-Valdecasas, JC and Heaton, N and Imber, C and Jassem, W and Jochmans, I and Karani, J and Knight, SR and Kocabayoglu, P and Malagò, M and Mirza, D and Morris, PJ and Pallan, A and Paul, A and Pavel, M and Perera, MTPR and Pirenne, J and Ravikumar, R and Russell, L and Upponi, S and Watson, CJE and Weissenbacher, A and Ploeg, RJ and Friend, PJ and , }, title = {A randomized trial of normothermic preservation in liver transplantation.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {50-56}, doi = {10.1038/s41586-018-0047-9}, pmid = {29670285}, issn = {1476-4687}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Allografts/pathology/*physiology/physiopathology/standards ; Bile Ducts/pathology/physiology/physiopathology ; Female ; Graft Survival ; Humans ; Length of Stay ; Liver/enzymology/*physiology ; Liver Transplantation/adverse effects/*methods ; Male ; Middle Aged ; Organ Preservation/adverse effects/*methods ; Perfusion ; Survival Analysis ; *Temperature ; Tissue Donors/supply & distribution ; Tissue and Organ Harvesting/adverse effects/*methods ; Treatment Outcome ; Waiting Lists ; Young Adult ; }, abstract = {Liver transplantation is a highly successful treatment, but is severely limited by the shortage in donor organs. However, many potential donor organs cannot be used; this is because sub-optimal livers do not tolerate conventional cold storage and there is no reliable way to assess organ viability preoperatively. Normothermic machine perfusion maintains the liver in a physiological state, avoids cooling and allows recovery and functional testing. Here we show that, in a randomized trial with 220 liver transplantations, compared to conventional static cold storage, normothermic preservation is associated with a 50% lower level of graft injury, measured by hepatocellular enzyme release, despite a 50% lower rate of organ discard and a 54% longer mean preservation time. There was no significant difference in bile duct complications, graft survival or survival of the patient. If translated to clinical practice, these results would have a major impact on liver transplant outcomes and waiting list mortality.}, } @article {pmid29670284, year = {2018}, author = {Houghton, IA and Koseff, JR and Monismith, SG and Dabiri, JO}, title = {Vertically migrating swimmers generate aggregation-scale eddies in a stratified column.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {497-500}, doi = {10.1038/s41586-018-0044-z}, pmid = {29670284}, issn = {1476-4687}, mesh = {Animals ; Artemia/*physiology ; *Diffusion ; Euphausiacea/physiology ; Seawater/*analysis/chemistry ; *Swimming ; Time Factors ; *Water Movements ; Zooplankton/physiology ; }, abstract = {Biologically generated turbulence has been proposed as an important contributor to nutrient transport and ocean mixing1-3. However, to produce non-negligible transport and mixing, such turbulence must produce eddies at scales comparable to the length scales of stratification in the ocean. It has previously been argued that biologically generated turbulence is limited to the scale of the individual animals involved 4 , which would make turbulence created by highly abundant centimetre-scale zooplankton such as krill irrelevant to ocean mixing. Their small size notwithstanding, zooplankton form dense aggregations tens of metres in vertical extent as they undergo diurnal vertical migration over hundreds of metres3,5,6. This behaviour potentially introduces additional length scales-such as the scale of the aggregation-that are of relevance to animal interactions with the surrounding water column. Here we show that the collective vertical migration of centimetre-scale swimmers-as represented by the brine shrimp Artemia salina-generates aggregation-scale eddies that mix a stable density stratification, resulting in an effective turbulent diffusivity up to three orders of magnitude larger than the molecular diffusivity of salt. These observed large-scale mixing eddies are the result of flow in the wakes of the individual organisms coalescing to form a large-scale downward jet during upward swimming, even in the presence of a strong density stratification relative to typical values observed in the ocean. The results illustrate the potential for marine zooplankton to considerably alter the physical and biogeochemical structure of the water column, with potentially widespread effects owing to their high abundance in climatically important regions of the ocean 7 .}, } @article {pmid29670283, year = {2018}, author = {Xu, J and Bartolome, CL and Low, CS and Yi, X and Chien, CH and Wang, P and Kong, D}, title = {Genetic identification of leptin neural circuits in energy and glucose homeostases.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {505-509}, pmid = {29670283}, issn = {1476-4687}, support = {R21 NS097922/NS/NINDS NIH HHS/United States ; K01 DK094943/DK/NIDDK NIH HHS/United States ; P30 DK046200/DK/NIDDK NIH HHS/United States ; P30 EY012196/EY/NEI NIH HHS/United States ; R01 DK108797/DK/NIDDK NIH HHS/United States ; P30 NS047243/NS/NINDS NIH HHS/United States ; T32 NS061764/NS/NINDS NIH HHS/United States ; }, mesh = {Agouti-Related Protein/metabolism ; Animals ; Blood Glucose/*metabolism ; Body Weight ; Diabetes Mellitus, Experimental/genetics/metabolism ; Eating ; *Energy Metabolism ; Female ; GABAergic Neurons/metabolism ; Gene Editing ; *Homeostasis ; Hyperglycemia/metabolism ; Hyperphagia/physiopathology ; Leptin/*metabolism ; Male ; Mice ; Neural Pathways/*physiology ; Neurons/*metabolism ; Obesity/genetics/metabolism ; Potassium Channels/metabolism ; Presynaptic Terminals/metabolism ; Receptors, Leptin/deficiency/genetics/metabolism ; Satiety Response ; }, abstract = {Leptin, a hormone produced in white adipose tissue, acts in the brain to communicate fuel status, suppress appetite following a meal, promote energy expenditure and maintain blood glucose stability1,2. Dysregulation of leptin or its receptors (LEPR) results in severe obesity and diabetes3-5. Although intensive studies on leptin have transformed obesity and diabetes research2,6, clinical applications of the molecule are still limited 7 , at least in part owing to the complexity and our incomplete understanding of the underlying neural circuits. The hypothalamic neurons that express agouti-related peptide (AGRP) and pro-opiomelanocortin (POMC) have been hypothesized to be the main first-order, leptin-responsive neurons. Selective deletion of LEPR in these neurons with the Cre-loxP system, however, has previously failed to recapitulate, or only marginally recapitulated, the obesity and diabetes that are seen in LEPR-deficient Lepr db/db mice, suggesting that AGRP or POMC neurons are not directly required for the effects of leptin in vivo8-10. The primary neural targets of leptin are therefore still unclear. Here we conduct a systematic, unbiased survey of leptin-responsive neurons in streptozotocin-induced diabetic mice and exploit CRISPR-Cas9-mediated genetic ablation of LEPR in vivo. Unexpectedly, we find that AGRP neurons but not POMC neurons are required for the primary action of leptin to regulate both energy balance and glucose homeostasis. Leptin deficiency disinhibits AGRP neurons, and chemogenetic inhibition of these neurons reverses both diabetic hyperphagia and hyperglycaemia. In sharp contrast to previous studies, we show that CRISPR-mediated deletion of LEPR in AGRP neurons causes severe obesity and diabetes, faithfully replicating the phenotype of Lepr db/db mice. We also uncover divergent mechanisms of acute and chronic inhibition of AGRP neurons by leptin (presynaptic potentiation of GABA (γ-aminobutyric acid) neurotransmission and postsynaptic activation of ATP-sensitive potassium channels, respectively). Our findings identify the underlying basis of the neurobiological effects of leptin and associated metabolic disorders.}, } @article {pmid29670282, year = {2018}, author = {Hughes, TP and Kerry, JT and Baird, AH and Connolly, SR and Dietzel, A and Eakin, CM and Heron, SF and Hoey, AS and Hoogenboom, MO and Liu, G and McWilliam, MJ and Pears, RJ and Pratchett, MS and Skirving, WJ and Stella, JS and Torda, G}, title = {Global warming transforms coral reef assemblages.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {492-496}, doi = {10.1038/s41586-018-0041-2}, pmid = {29670282}, issn = {1476-4687}, mesh = {Animals ; Anthozoa/classification/*growth & development ; Australia ; *Coral Reefs ; *Global Warming ; Hot Temperature/adverse effects ; Population Dynamics ; }, abstract = {Global warming is rapidly emerging as a universal threat to ecological integrity and function, highlighting the urgent need for a better understanding of the impact of heat exposure on the resilience of ecosystems and the people who depend on them 1 . Here we show that in the aftermath of the record-breaking marine heatwave on the Great Barrier Reef in 2016 2 , corals began to die immediately on reefs where the accumulated heat exposure exceeded a critical threshold of degree heating weeks, which was 3-4 °C-weeks. After eight months, an exposure of 6 °C-weeks or more drove an unprecedented, regional-scale shift in the composition of coral assemblages, reflecting markedly divergent responses to heat stress by different taxa. Fast-growing staghorn and tabular corals suffered a catastrophic die-off, transforming the three-dimensionality and ecological functioning of 29% of the 3,863 reefs comprising the world's largest coral reef system. Our study bridges the gap between the theory and practice of assessing the risk of ecosystem collapse, under the emerging framework for the International Union for Conservation of Nature (IUCN) Red List of Ecosystems 3 , by rigorously defining both the initial and collapsed states, identifying the major driver of change, and establishing quantitative collapse thresholds. The increasing prevalence of post-bleaching mass mortality of corals represents a radical shift in the disturbance regimes of tropical reefs, both adding to and far exceeding the influence of recurrent cyclones and other local pulse events, presenting a fundamental challenge to the long-term future of these iconic ecosystems.}, } @article {pmid29670281, year = {2018}, author = {Pastushenko, I and Brisebarre, A and Sifrim, A and Fioramonti, M and Revenco, T and Boumahdi, S and Van Keymeulen, A and Brown, D and Moers, V and Lemaire, S and De Clercq, S and Minguijón, E and Balsat, C and Sokolow, Y and Dubois, C and De Cock, F and Scozzaro, S and Sopena, F and Lanas, A and D'Haene, N and Salmon, I and Marine, JC and Voet, T and Sotiropoulou, PA and Blanpain, C}, title = {Identification of the tumour transition states occurring during EMT.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {463-468}, doi = {10.1038/s41586-018-0040-3}, pmid = {29670281}, issn = {1476-4687}, support = {15-0270//Worldwide Cancer Research/United Kingdom ; }, mesh = {Animals ; Chromatin/genetics ; Epigenesis, Genetic ; Epithelial Cells/metabolism/pathology ; *Epithelial-Mesenchymal Transition/genetics ; Female ; Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks ; Humans ; Male ; Mammary Neoplasms, Animal/genetics/pathology ; Mesoderm/metabolism/pathology ; Mice ; Neoplasm Invasiveness/genetics/pathology ; Neoplasm Metastasis/genetics/pathology ; Neoplasms/genetics/*pathology ; Signal Transduction ; Skin Neoplasms/genetics/pathology ; Transcription, Genetic ; }, abstract = {In cancer, the epithelial-to-mesenchymal transition (EMT) is associated with tumour stemness, metastasis and resistance to therapy. It has recently been proposed that, rather than being a binary process, EMT occurs through distinct intermediate states. However, there is no direct in vivo evidence for this idea. Here we screen a large panel of cell surface markers in skin and mammary primary tumours, and identify the existence of multiple tumour subpopulations associated with different EMT stages: from epithelial to completely mesenchymal states, passing through intermediate hybrid states. Although all EMT subpopulations presented similar tumour-propagating cell capacity, they displayed differences in cellular plasticity, invasiveness and metastatic potential. Their transcriptional and epigenetic landscapes identify the underlying gene regulatory networks, transcription factors and signalling pathways that control these different EMT transition states. Finally, these tumour subpopulations are localized in different niches that differentially regulate EMT transition states.}, } @article {pmid29670280, year = {2018}, author = {Song, X and Jensen, MØ and Jogini, V and Stein, RA and Lee, CH and Mchaourab, HS and Shaw, DE and Gouaux, E}, title = {Mechanism of NMDA receptor channel block by MK-801 and memantine.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {515-519}, pmid = {29670280}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 NS038631/NS/NINDS NIH HHS/United States ; }, mesh = {Alzheimer Disease/drug therapy ; Animals ; Binding Sites ; Crystallography, X-Ray ; Dizocilpine Maleate/chemistry/*pharmacology ; Ion Channel Gating/*drug effects ; Memantine/chemistry/*pharmacology ; Molecular Dynamics Simulation ; Protein Domains ; Receptors, AMPA/chemistry/metabolism ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors/chemistry/metabolism ; Substrate Specificity ; Xenopus ; }, abstract = {The NMDA (N-methyl-D-aspartate) receptor transduces the binding of glutamate and glycine, coupling it to the opening of a calcium-permeable ion channel 1 . Owing to the lack of high-resolution structural studies of the NMDA receptor, the mechanism by which ion-channel blockers occlude ion permeation is not well understood. Here we show that removal of the amino-terminal domains from the GluN1-GluN2B NMDA receptor yields a functional receptor and crystals with good diffraction properties, allowing us to map the binding site of the NMDA receptor blocker, MK-801. This crystal structure, together with long-timescale molecular dynamics simulations, shows how MK-801 and memantine (a drug approved for the treatment of Alzheimer's disease) bind within the vestibule of the ion channel, promote closure of the ion channel gate and lodge between the M3-helix-bundle crossing and the M2-pore loops, physically blocking ion permeation.}, } @article {pmid29670277, year = {2018}, author = {}, title = {Second March for Science, flesh-eating virus and protein fraud.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {278-279}, doi = {10.1038/d41586-018-04599-y}, pmid = {29670277}, issn = {1476-4687}, } @article {pmid29670276, year = {2018}, author = {Gibney, E}, title = {How to blow up a star.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {287-289}, doi = {10.1038/d41586-018-04601-7}, pmid = {29670276}, issn = {1476-4687}, } @article {pmid29670275, year = {2018}, author = {Schiermeier, Q}, title = {Great Barrier Reef saw huge losses from 2016 heatwave.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {281-282}, doi = {10.1038/d41586-018-04660-w}, pmid = {29670275}, issn = {1476-4687}, mesh = {Anthozoa ; Australia ; *Climate Change ; *Coral Reefs ; Infrared Rays ; }, } @article {pmid29670274, year = {2018}, author = {Rougier, NP and Hinsen, K}, title = {Code reviewing puts extra demands on referees.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {309}, doi = {10.1038/d41586-018-04628-w}, pmid = {29670274}, issn = {1476-4687}, mesh = {*Peer Review, Research ; *Programming Languages ; *Software ; }, } @article {pmid29670273, year = {2018}, author = {Watkins, J and Wulaningsih, W}, title = {Steer cancer funding to align with clinical goals.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {309}, doi = {10.1038/d41586-018-04636-w}, pmid = {29670273}, issn = {1476-4687}, mesh = {*Goals ; Humans ; *Neoplasms ; }, } @article {pmid29670272, year = {2018}, author = {de Carli, GJ and Campos Pereira, T}, title = {Sharp rise in premier papers from Brazilian universities.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {309}, doi = {10.1038/d41586-018-04634-y}, pmid = {29670272}, issn = {1476-4687}, mesh = {*Bibliometrics ; Brazil ; Periodicals as Topic/standards ; Research/*standards/*statistics & numerical data ; Research Report/*standards/trends ; *Universities ; }, } @article {pmid29670271, year = {2018}, author = {Swainston, N and Kettner, C}, title = {A repository for quality-assured data on enzyme activity.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {309}, doi = {10.1038/d41586-018-04630-2}, pmid = {29670271}, issn = {1476-4687}, mesh = {*Data Accuracy ; *Databases, Factual ; Enzymes/*metabolism ; }, } @article {pmid29670270, year = {2018}, author = {Norton, L}, title = {Long-term tracking of biodiversity is more important than ever.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {309}, doi = {10.1038/d41586-018-04626-y}, pmid = {29670270}, issn = {1476-4687}, mesh = {*Biodiversity ; *Botany ; Environmental Monitoring/*methods ; *Observation ; *Plants ; *Surveys and Questionnaires ; United Kingdom ; Workforce ; }, } @article {pmid29670269, year = {2018}, author = {}, title = {A welcome framework for research in Africa.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {274}, doi = {10.1038/d41586-018-04589-0}, pmid = {29670269}, issn = {1476-4687}, mesh = {Africa ; Developing Countries ; *Ethics, Research ; Genomics/*ethics/*organization & administration ; Humans ; Research/*organization & administration ; Research Personnel/ethics/*organization & administration ; Research Support as Topic/ethics/organization & administration ; Workforce ; }, } @article {pmid29670268, year = {2018}, author = {Schaal, A}, title = {Science must rise up to support people like me.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {275}, doi = {10.1038/d41586-018-04598-z}, pmid = {29670268}, issn = {1476-4687}, mesh = {Adult ; Amino Acid Metabolism, Inborn Errors/*physiopathology ; Brain Diseases, Metabolic/*physiopathology ; Child, Preschool ; *Disabled Persons ; Glutaryl-CoA Dehydrogenase/*deficiency ; Humans ; Male ; Physics ; Prejudice/*prevention & control ; *Research Personnel ; *Science ; Wheelchairs/statistics & numerical data ; Workforce ; }, } @article {pmid29670266, year = {2018}, author = {Thielking, J and Okhapkin, MV and Głowacki, P and Meier, DM and von der Wense, L and Seiferle, B and Düllmann, CE and Thirolf, PG and Peik, E}, title = {Laser spectroscopic characterization of the nuclear-clock isomer 229mTh.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {321-325}, doi = {10.1038/s41586-018-0011-8}, pmid = {29670266}, issn = {1476-4687}, abstract = {The isotope 229Th is the only nucleus known to possess an excited state 229mTh in the energy range of a few electronvolts-a transition energy typical for electrons in the valence shell of atoms, but about four orders of magnitude lower than typical nuclear excitation energies. Of the many applications that have been proposed for this nuclear system, which is accessible by optical methods, the most promising is a highly precise nuclear clock that outperforms existing atomic timekeepers. Here we present the laser spectroscopic investigation of the hyperfine structure of the doubly charged 229mTh ion and the determination of the fundamental nuclear properties of the isomer, namely, its magnetic dipole and electric quadrupole moments, as well as its nuclear charge radius. Following the recent direct detection of this long-sought isomer, we provide detailed insight into its nuclear structure and present a method for its non-destructive optical detection.}, } @article {pmid29670265, year = {2018}, author = {Lee, HE and Ahn, HY and Mun, J and Lee, YY and Kim, M and Cho, NH and Chang, K and Kim, WS and Rho, J and Nam, KT}, title = {Amino-acid- and peptide-directed synthesis of chiral plasmonic gold nanoparticles.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {360-365}, doi = {10.1038/s41586-018-0034-1}, pmid = {29670265}, issn = {1476-4687}, mesh = {Amino Acids/*chemistry ; Chemistry Techniques, Synthetic/*methods ; Circular Dichroism ; Cysteine/chemistry ; Gold/*chemistry/radiation effects ; Light ; Metal Nanoparticles/*chemistry/radiation effects ; Optical Rotation ; Peptides/*chemistry ; Photometry ; Stereoisomerism ; }, abstract = {Understanding chirality, or handedness, in molecules is important because of the enantioselectivity that is observed in many biochemical reactions 1 , and because of the recent development of chiral metamaterials with exceptional light-manipulating capabilities, such as polarization control2-4, a negative refractive index 5 and chiral sensing 6 . Chiral nanostructures have been produced using nanofabrication techniques such as lithography 7 and molecular self-assembly8-11, but large-scale and simple fabrication methods for three-dimensional chiral structures remain a challenge. In this regard, chirality transfer represents a simpler and more efficient method for controlling chiral morphology12-18. Although a few studies18,19 have described the transfer of molecular chirality into micrometre-sized helical ceramic crystals, this technique has yet to be implemented for metal nanoparticles with sizes of hundreds of nanometres. Here we develop a strategy for synthesizing chiral gold nanoparticles that involves using amino acids and peptides to control the optical activity, handedness and chiral plasmonic resonance of the nanoparticles. The key requirement for achieving such chiral structures is the formation of high-Miller-index surfaces ({hkl}, h ≠ k ≠ l ≠ 0) that are intrinsically chiral, owing to the presence of 'kink' sites20-22 in the nanoparticles during growth. The presence of chiral components at the inorganic surface of the nanoparticles and in the amino acids and peptides results in enantioselective interactions at the interface between these elements; these interactions lead to asymmetric evolution of the nanoparticles and the formation of helicoid morphologies that consist of highly twisted chiral elements. The gold nanoparticles that we grow display strong chiral plasmonic optical activity (a dis-symmetry factor of 0.2), even when dispersed randomly in solution; this observation is supported by theoretical calculations and direct visualizations of macroscopic colour transformations. We anticipate that our strategy will aid in the rational design and fabrication of three-dimensional chiral nanostructures for use in plasmonic metamaterial applications.}, } @article {pmid29670264, year = {2018}, author = {Müller-Sánchez, F and Nevin, R and Comerford, JM and Davies, RI and Privon, GC and Treister, E}, title = {Two separate outflows in the dual supermassive black hole system NGC 6240.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {345-348}, doi = {10.1038/s41586-018-0033-2}, pmid = {29670264}, issn = {1476-4687}, abstract = {Theoretical models and numerical simulations have established a framework of galaxy evolution in which galaxies merge and create dual supermassive black holes (with separations of one to ten kiloparsecs), which eventually sink into the centre of the merger remnant, emit gravitational waves and coalesce. The merger also triggers star formation and supermassive black hole growth, and gas outflows regulate the stellar content1-3. Although this theoretical picture is supported by recent observations of starburst-driven and supermassive black hole-driven outflows4-6, it remains unclear how these outflows interact with the interstellar medium. Furthermore, the relative contributions of star formation and black hole activity to galactic feedback remain unknown7-9. Here we report observations of dual outflows in the central region of the prototypical merger NGC 6240. We find a black-hole-driven outflow of [O III] to the northeast and a starburst-driven outflow of Hα to the northwest. The orientations and positions of the outflows allow us to isolate them spatially and study their properties independently. We estimate mass outflow rates of 10 and 75 solar masses per year for the Hα bubble and the [O III] cone, respectively. Their combined mass outflow is comparable to the star formation rate 10 , suggesting that negative feedback on star formation is occurring.}, } @article {pmid29670263, year = {2018}, author = {Zhou, J and Lin, J and Huang, X and Zhou, Y and Chen, Y and Xia, J and Wang, H and Xie, Y and Yu, H and Lei, J and Wu, D and Liu, F and Fu, Q and Zeng, Q and Hsu, CH and Yang, C and Lu, L and Yu, T and Shen, Z and Lin, H and Yakobson, BI and Liu, Q and Suenaga, K and Liu, G and Liu, Z}, title = {A library of atomically thin metal chalcogenides.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {355-359}, doi = {10.1038/s41586-018-0008-3}, pmid = {29670263}, issn = {1476-4687}, abstract = {Investigations of two-dimensional transition-metal chalcogenides (TMCs) have recently revealed interesting physical phenomena, including the quantum spin Hall effect1,2, valley polarization3,4 and two-dimensional superconductivity 5 , suggesting potential applications for functional devices6-10. However, of the numerous compounds available, only a handful, such as Mo- and W-based TMCs, have been synthesized, typically via sulfurization11-15, selenization16,17 and tellurization 18 of metals and metal compounds. Many TMCs are difficult to produce because of the high melting points of their metal and metal oxide precursors. Molten-salt-assisted methods have been used to produce ceramic powders at relatively low temperature 19 and this approach 20 was recently employed to facilitate the growth of monolayer WS2 and WSe2. Here we demonstrate that molten-salt-assisted chemical vapour deposition can be broadly applied for the synthesis of a wide variety of two-dimensional (atomically thin) TMCs. We synthesized 47 compounds, including 32 binary compounds (based on the transition metals Ti, Zr, Hf, V, Nb, Ta, Mo, W, Re, Pt, Pd and Fe), 13 alloys (including 11 ternary, one quaternary and one quinary), and two heterostructured compounds. We elaborate how the salt decreases the melting point of the reactants and facilitates the formation of intermediate products, increasing the overall reaction rate. Most of the synthesized materials in our library are useful, as supported by evidence of superconductivity in our monolayer NbSe2 and MoTe2 samples21,22 and of high mobilities in MoS2 and ReS2. Although the quality of some of the materials still requires development, our work opens up opportunities for studying the properties and potential application of a wide variety of two-dimensional TMCs.}, } @article {pmid29670262, year = {2018}, author = {Atabaki, AH and Moazeni, S and Pavanello, F and Gevorgyan, H and Notaros, J and Alloatti, L and Wade, MT and Sun, C and Kruger, SA and Meng, H and Al Qubaisi, K and Wang, I and Zhang, B and Khilo, A and Baiocco, CV and Popović, MA and Stojanović, VM and Ram, RJ}, title = {Integrating photonics with silicon nanoelectronics for the next generation of systems on a chip.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {349-354}, doi = {10.1038/s41586-018-0028-z}, pmid = {29670262}, issn = {1476-4687}, abstract = {Electronic and photonic technologies have transformed our lives-from computing and mobile devices, to information technology and the internet. Our future demands in these fields require innovation in each technology separately, but also depend on our ability to harness their complementary physics through integrated solutions1,2. This goal is hindered by the fact that most silicon nanotechnologies-which enable our processors, computer memory, communications chips and image sensors-rely on bulk silicon substrates, a cost-effective solution with an abundant supply chain, but with substantial limitations for the integration of photonic functions. Here we introduce photonics into bulk silicon complementary metal-oxide-semiconductor (CMOS) chips using a layer of polycrystalline silicon deposited on silicon oxide (glass) islands fabricated alongside transistors. We use this single deposited layer to realize optical waveguides and resonators, high-speed optical modulators and sensitive avalanche photodetectors. We integrated this photonic platform with a 65-nanometre-transistor bulk CMOS process technology inside a 300-millimetre-diameter-wafer microelectronics foundry. We then implemented integrated high-speed optical transceivers in this platform that operate at ten gigabits per second, composed of millions of transistors, and arrayed on a single optical bus for wavelength division multiplexing, to address the demand for high-bandwidth optical interconnects in data centres and high-performance computing3,4. By decoupling the formation of photonic devices from that of transistors, this integration approach can achieve many of the goals of multi-chip solutions 5 , but with the performance, complexity and scalability of 'systems on a chip'1,6-8. As transistors smaller than ten nanometres across become commercially available 9 , and as new nanotechnologies emerge10,11, this approach could provide a way to integrate photonics with state-of-the-art nanoelectronics.}, } @article {pmid29670201, year = {2018}, author = {}, title = {At the end of KSHV's tether.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {331}, doi = {10.1038/s41579-018-0017-0}, pmid = {29670201}, issn = {1740-1534}, } @article {pmid29669926, year = {2018}, author = {Palmer, S and Albergante, L and Blackburn, CC and Newman, TJ}, title = {Reply to Jiménez-Alonso et al., Schooling and Zhao, and Mortazavi: Further discussion on the immunological model of carcinogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4319-E4321}, pmid = {29669926}, issn = {1091-6490}, mesh = {*Carcinogenesis ; Humans ; *Models, Immunological ; }, } @article {pmid29669925, year = {2018}, author = {Barrera-Guzmán, AO and Aleixo, A and Shawkey, MD and Weir, JT}, title = {Reply to Rosenthal et al.: Both premating and postmating isolation likely contributed to manakin hybrid speciation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4146-E4147}, pmid = {29669925}, issn = {1091-6490}, mesh = {Biological Evolution ; *Genetic Speciation ; Hybridization, Genetic ; Reproduction ; *Reproductive Isolation ; }, } @article {pmid29669924, year = {2018}, author = {Thientosapol, ES and Bosnjak, D and Durack, T and Stevanovski, I and van Geldermalsen, M and Holst, J and Jahan, Z and Shepard, C and Weninger, W and Kim, B and Brink, R and Jolly, CJ}, title = {SAMHD1 enhances immunoglobulin hypermutation by promoting transversion mutation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4921-4926}, pmid = {29669924}, issn = {1091-6490}, support = {R01 AI049781/AI/NIAID NIH HHS/United States ; R01 GM104198/GM/NIGMS NIH HHS/United States ; R56 AI049781/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; B-Lymphocytes/cytology/*immunology ; Cytidine Deaminase/immunology ; G1 Phase/genetics/*immunology ; *Lymphocyte Activation ; Male ; Mice ; Mice, Transgenic ; *Mutation ; Nucleotidyltransferases/genetics/immunology ; *SAM Domain and HD Domain-Containing Protein 1/genetics/immunology ; Somatic Hypermutation, Immunoglobulin/*immunology ; }, abstract = {Activation-induced deaminase (AID) initiates hypermutation of Ig genes in activated B cells by converting C:G into U:G base pairs. G1-phase variants of uracil base excision repair (BER) and mismatch repair (MMR) then deploy translesion polymerases including REV1 and Pol η, which exacerbates mutation. dNTP paucity may contribute to hypermutation, because dNTP levels are reduced in G1 phase to inhibit viral replication. To derestrict G1-phase dNTP supply, we CRISPR-inactivated SAMHD1 (which degrades dNTPs) in germinal center B cells. Samhd1 inactivation increased B cell virus susceptibility, increased transition mutations at C:G base pairs, and substantially decreased transversion mutations at A:T and C:G base pairs in both strands. We conclude that SAMHD1's restriction of dNTP supply enhances AID's mutagenicity and that the evolution of Ig hypermutation included the repurposing of antiviral mechanisms based on dNTP starvation.}, } @article {pmid29669923, year = {2018}, author = {Bauer, D and Meinhold, S and Jakob, RP and Stigler, J and Merkel, U and Maier, T and Rief, M and Žoldák, G}, title = {A folding nucleus and minimal ATP binding domain of Hsp70 identified by single-molecule force spectroscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4666-4671}, pmid = {29669923}, issn = {1091-6490}, mesh = {Actins/*chemistry/metabolism ; Adenosine Triphosphate/*chemistry/metabolism ; Escherichia coli/*chemistry/metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; HSP70 Heat-Shock Proteins/*chemistry/metabolism ; Protein Domains ; *Protein Folding ; *Single Molecule Imaging ; }, abstract = {The folding pathways of large proteins are complex, with many of them requiring the aid of chaperones and others folding spontaneously. Along the folding pathways, partially folded intermediates are frequently populated; their role in the driving of the folding process is unclear. The structures of these intermediates are generally not amenable to high-resolution structural techniques because of their transient nature. Here we employed single-molecule force measurements to scrutinize the hierarchy of intermediate structures along the folding pathway of the nucleotide binding domain (NBD) of Escherichia coli Hsp70 DnaK. DnaK-NBD is a member of the sugar kinase superfamily that includes Hsp70s and the cytoskeletal protein actin. Using optical tweezers, a stable nucleotide-binding competent en route folding intermediate comprising lobe II residues (183-383) was identified as a critical checkpoint for productive folding. We obtained a structural snapshot of this folding intermediate that shows native-like conformation. To assess the fundamental role of folded lobe II for efficient folding, we turned our attention to yeast mitochondrial NBD, which does not fold without a dedicated chaperone. After replacing the yeast lobe II residues with stable E. coli lobe II, the obtained chimeric protein showed native-like ATPase activity and robust folding into the native state, even in the absence of chaperone. In summary, lobe II is a stable nucleotide-binding competent folding nucleus that is the key to time-efficient folding and possibly resembles a common ancestor domain. Our findings provide a conceptual framework for the folding pathways of other members of this protein superfamily.}, } @article {pmid29669922, year = {2018}, author = {Yin, X and Ying, D and Lhomme, S and Tang, Z and Walker, CM and Xia, N and Zheng, Z and Feng, Z}, title = {Origin, antigenicity, and function of a secreted form of ORF2 in hepatitis E virus infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4773-4778}, pmid = {29669922}, issn = {1091-6490}, support = {R21 AI122228/AI/NIAID NIH HHS/United States ; R21 AI137912/AI/NIAID NIH HHS/United States ; S10 OD018056/OD/NIH HHS/United States ; }, mesh = {Codon, Initiator/immunology ; Epitopes/genetics/*immunology ; Hep G2 Cells ; Hepatitis Antigens/genetics/*immunology ; Hepatitis E/genetics/*immunology/pathology ; Hepatitis E virus/genetics/*immunology ; Humans ; Protein Biosynthesis/genetics/*immunology ; Viral Proteins/genetics/*immunology ; }, abstract = {The enterically transmitted hepatitis E virus (HEV) adopts a unique strategy to exit cells by cloaking its capsid (encoded by the viral ORF2 gene) and circulating in the blood as "quasi-enveloped" particles. However, recent evidence suggests that the majority of the ORF2 protein present in the patient serum and supernatants of HEV-infected cell culture exists in a free form and is not associated with virus particles. The origin and biological functions of this secreted form of ORF2 (ORF2S) are unknown. Here we show that production of ORF2S results from translation initiated at the previously presumed AUG start codon for the capsid protein, whereas translation of the actual capsid protein (ORF2C) is initiated at a previously unrecognized internal AUG codon (15 codons downstream of the first AUG). The addition of 15 amino acids to the N terminus of the capsid protein creates a signal sequence that drives ORF2S secretion via the secretory pathway. Unlike ORF2C, ORF2S is glycosylated and exists as a dimer. Nonetheless, ORF2S exhibits substantial antigenic overlap with the capsid, but the epitopes predicted to bind the putative cell receptor are lost. Consistent with this, ORF2S does not block HEV cell entry but inhibits antibody-mediated neutralization. These results reveal a previously unrecognized aspect in HEV biology and shed new light on the immune evasion mechanisms and pathogenesis of this virus.}, } @article {pmid29669921, year = {2018}, author = {Koster, AK and Wood, CAP and Thomas-Tran, R and Chavan, TS and Almqvist, J and Choi, KH and Du Bois, J and Maduke, M}, title = {A selective class of inhibitors for the CLC-Ka chloride ion channel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {21}, pages = {E4900-E4909}, pmid = {29669921}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Binding Sites ; Chloride Channels/*antagonists & inhibitors/genetics/metabolism ; Chlorides/*metabolism ; Electrophysiology ; Humans ; Ion Channel Gating/*drug effects ; Molecular Docking Simulation ; Mutagenesis, Site-Directed ; Mutation ; Protein Conformation ; Small Molecule Libraries/*pharmacology ; Structure-Activity Relationship ; Xenopus laevis ; }, abstract = {CLC proteins are a ubiquitously expressed family of chloride-selective ion channels and transporters. A dearth of pharmacological tools for modulating CLC gating and ion conduction limits investigations aimed at understanding CLC structure/function and physiology. Herein, we describe the design, synthesis, and evaluation of a collection of N-arylated benzimidazole derivatives (BIMs), one of which (BIM1) shows unparalleled (>20-fold) selectivity for CLC-Ka over CLC-Kb, the two most closely related human CLC homologs. Computational docking to a CLC-Ka homology model has identified a BIM1 binding site on the extracellular face of the protein near the chloride permeation pathway in a region previously identified as a binding site for other less selective inhibitors. Results from site-directed mutagenesis experiments are consistent with predictions of this docking model. The residue at position 68 is 1 of only ∼20 extracellular residues that differ between CLC-Ka and CLC-Kb. Mutation of this residue in CLC-Ka and CLC-Kb (N68D and D68N, respectively) reverses the preference of BIM1 for CLC-Ka over CLC-Kb, thus showing the critical role of residue 68 in establishing BIM1 selectivity. Molecular docking studies together with results from structure-activity relationship studies with 19 BIM derivatives give insight into the increased selectivity of BIM1 compared with other inhibitors and identify strategies for further developing this class of compounds.}, } @article {pmid29669920, year = {2018}, author = {Huang, W and Haferkamp, I and Lepetit, B and Molchanova, M and Hou, S and Jeblick, W and Río Bártulos, C and Kroth, PG}, title = {Reduced vacuolar β-1,3-glucan synthesis affects carbohydrate metabolism as well as plastid homeostasis and structure in Phaeodactylum tricornutum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4791-4796}, pmid = {29669920}, issn = {1091-6490}, mesh = {Carbohydrate Metabolism/*physiology ; Diatoms/genetics/*metabolism ; Glucosyltransferases/metabolism ; Homeostasis/*physiology ; Photosynthesis/*physiology ; Thylakoids/*metabolism ; beta-Glucans/*metabolism ; }, abstract = {The β-1,3-glucan chrysolaminarin is the main storage polysaccharide of diatoms. In contrast to plants and green algae, diatoms and most other algal groups do not accumulate storage polysaccharides in their plastids. The diatom Phaeodactylum tricornutum possesses only a single gene encoding a putative β-1,3-glucan synthase (PtBGS). Here, we characterize this enzyme by expressing GFP fusion proteins in P. tricornutum and by creating and investigating corresponding gene silencing mutants. We demonstrate that PtBGS is a vacuolar protein located in the tonoplast. Metabolite analyses of two mutant strains with reduced amounts of PtBGS reveal a reduction in their chrysolaminarin content and an increase of soluble sugars and lipids. This indicates that carbohydrates are shunted into alternative pathways when chrysolaminarin production is impaired. The mutant strains show reduced growth and lower photosynthetic capacities, while possessing higher photoprotective abilities than WT cells. Interestingly, a strong reduction in PtBGS expression also results in aberrations of the usually very regular thylakoid membrane patterns, including increased thylakoid thickness, reduced numbers of thylakoids per plastid, and increased numbers of lamellae per thylakoid stack. Our data demonstrate the complex intertwinement of carbohydrate storage in the vacuoles with carbohydrate metabolism, photosynthetic homeostasis, and plastid morphology.}, } @article {pmid29669919, year = {2018}, author = {Tamura, K and Yu, J and Hata, T and Suenaga, M and Shindo, K and Abe, T and MacGregor-Das, A and Borges, M and Wolfgang, CL and Weiss, MJ and He, J and Canto, MI and Petersen, GM and Gallinger, S and Syngal, S and Brand, RE and Rustgi, A and Olson, SH and Stoffel, E and Cote, ML and Zogopoulos, G and Potash, JB and Goes, FS and McCombie, RW and Zandi, PP and Pirooznia, M and Kramer, M and Parla, J and Eshleman, JR and Roberts, NJ and Hruban, RH and Klein, AP and Goggins, M}, title = {Mutations in the pancreatic secretory enzymes CPA1 and CPB1 are associated with pancreatic cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4767-4772}, pmid = {29669919}, issn = {1091-6490}, support = {R01 CA176828/CA/NCI NIH HHS/United States ; P50 CA062924/CA/NCI NIH HHS/United States ; R00 CA190889/CA/NCI NIH HHS/United States ; R01 CA132829/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; U01 CA210170/CA/NCI NIH HHS/United States ; K99 CA190889/CA/NCI NIH HHS/United States ; P50 CA102701/CA/NCI NIH HHS/United States ; P30 CA022453/CA/NCI NIH HHS/United States ; R01 CA154823/CA/NCI NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; *Carboxypeptidase B/genetics/metabolism ; *Carboxypeptidases A/genetics/metabolism ; Cell Line, Tumor ; Endoplasmic Reticulum Stress/*genetics ; Female ; *Genetic Predisposition to Disease ; Humans ; Male ; Middle Aged ; *Mutation ; *Neoplasm Proteins/genetics/metabolism ; *Pancreatic Neoplasms/enzymology/genetics/pathology ; }, abstract = {To evaluate whether germline variants in genes encoding pancreatic secretory enzymes contribute to pancreatic cancer susceptibility, we sequenced the coding regions of CPB1 and other genes encoding pancreatic secretory enzymes and known pancreatitis susceptibility genes (PRSS1, CPA1, CTRC, and SPINK1) in a hospital series of pancreatic cancer cases and controls. Variants in CPB1, CPA1 (encoding carboxypeptidase B1 and A1), and CTRC were evaluated in a second set of cases with familial pancreatic cancer and controls. More deleterious CPB1 variants, defined as having impaired protein secretion and induction of endoplasmic reticulum (ER) stress in transfected HEK 293T cells, were found in the hospital series of pancreatic cancer cases (5/986, 0.5%) than in controls (0/1,045, P = 0.027). Among familial pancreatic cancer cases, ER stress-inducing CPB1 variants were found in 4 of 593 (0.67%) vs. 0 of 967 additional controls (P = 0.020), with a combined prevalence in pancreatic cancer cases of 9/1,579 vs. 0/2,012 controls (P < 0.01). More ER stress-inducing CPA1 variants were also found in the combined set of hospital and familial cases with pancreatic cancer than in controls [7/1,546 vs. 1/2,012; P = 0.025; odds ratio, 9.36 (95% CI, 1.15-76.02)]. Overall, 16 (1%) of 1,579 pancreatic cancer cases had an ER stress-inducing CPA1 or CPB1 variant, compared with 1 of 2,068 controls (P < 0.00001). No other candidate genes had statistically significant differences in variant prevalence between cases and controls. Our study indicates ER stress-inducing variants in CPB1 and CPA1 are associated with pancreatic cancer susceptibility and implicate ER stress in pancreatic acinar cells in pancreatic cancer development.}, } @article {pmid29669918, year = {2018}, author = {Metzger, MJ and Paynter, AN and Siddall, ME and Goff, SP}, title = {Horizontal transfer of retrotransposons between bivalves and other aquatic species of multiple phyla.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4227-E4235}, pmid = {29669918}, issn = {1091-6490}, support = {T32 CA009503/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Bivalvia/*genetics ; *Gene Transfer, Horizontal ; *Genome ; *Retroelements ; }, abstract = {The LTR retrotransposon Steamer is a selfish endogenous element in the soft-shell clam genome that was first detected because of its dramatic amplification in bivalve transmissible neoplasia afflicting the species. We amplified and sequenced related retrotransposons from the genomic DNA of many other bivalve species, finding evidence of horizontal transfer of retrotransposons from the genome of one species to another. First, the phylogenetic tree of the Steamer-like elements from 19 bivalve species is markedly discordant with host phylogeny, suggesting frequent cross-species transfer throughout bivalve evolution. Second, sequences nearly identical to Steamer were identified in the genomes of Atlantic razor clams and Baltic clams, indicating recent transfer. Finally, a search of the National Center for Biotechnology Information sequence database revealed that Steamer-like elements are present in the genomes of completely unrelated organisms, including zebrafish, sea urchin, acorn worms, and coral. Phylogenetic incongruity, a patchy distribution, and a higher similarity than would be expected by vertical inheritance all provide evidence for multiple long-distance cross-phyla horizontal transfer events. These data suggest that over both short- and long-term evolutionary timescales, Steamer-like retrotransposons, much like retroviruses, can move between organisms and integrate new copies into new host genomes.}, } @article {pmid29669917, year = {2018}, author = {Udugama, M and Sanij, E and Voon, HPJ and Son, J and Hii, L and Henson, JD and Chan, FL and Chang, FTM and Liu, Y and Pearson, RB and Kalitsis, P and Mann, JR and Collas, P and Hannan, RD and Wong, LH}, title = {Ribosomal DNA copy loss and repeat instability in ATRX-mutated cancers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4737-4742}, pmid = {29669917}, issn = {1091-6490}, mesh = {Benzothiazoles/pharmacology ; Cell Line, Tumor ; DNA, Neoplasm/genetics/*metabolism ; DNA, Ribosomal/genetics/*metabolism ; *Gene Dosage ; Genomic Instability ; Humans ; *Mutation ; Naphthyridines/pharmacology ; Neoplasm Proteins/genetics/*metabolism ; Neoplasms/genetics/*metabolism/pathology ; RNA Polymerase I/antagonists & inhibitors/genetics/metabolism ; Transcription, Genetic/drug effects/genetics ; X-linked Nuclear Protein/genetics/*metabolism ; }, abstract = {ATRX (alpha thalassemia/mental retardation X-linked) complexes with DAXX to deposit histone variant H3.3 into repetitive heterochromatin. Recent genome sequencing studies in cancers have revealed mutations in ATRX and their association with ALT (alternative lengthening of telomeres) activation. Here we report depletion of ATRX in mouse ES cells leads to selective loss in ribosomal RNA gene (rDNA) copy number. Supporting this, ATRX-mutated human ALT-positive tumors also show a substantially lower rDNA copy than ALT-negative tumors. Further investigation shows that the rDNA copy loss and repeat instability are caused by a disruption in H3.3 deposition and thus a failure in heterochromatin formation at rDNA repeats in the absence of ATRX. We also find that ATRX-depleted cells are reduced in ribosomal RNA transcription output and show increased sensitivity to RNA polymerase I (Pol I) transcription inhibitor CX5461. In addition, human ALT-positive cancer cell lines are also more sensitive to CX5461 treatment. Our study provides insights into the contribution of ATRX loss of function to tumorigenesis through the loss of rDNA stability and suggests the therapeutic potential of targeting Pol I transcription in ALT cancers.}, } @article {pmid29669916, year = {2018}, author = {Mortazavi, SMJ}, title = {Shortcomings of the immunological model of carcinogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4318}, pmid = {29669916}, issn = {1091-6490}, mesh = {*Carcinogenesis ; Humans ; *Models, Immunological ; }, } @article {pmid29669915, year = {2018}, author = {Schooling, CM and Zhao, JV}, title = {Strengthening the immune system for cancer prevention.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4316-E4317}, pmid = {29669915}, issn = {1091-6490}, mesh = {*Delivery of Health Care ; Humans ; *Immune System ; Neoplasms ; }, } @article {pmid29669914, year = {2018}, author = {Jiménez-Alonso, JJ and Calderón-Montaño, JM and López-Lázaro, M}, title = {Are most cancer cases a consequence of an immune deficiency caused by thymic involution?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4314-E4315}, pmid = {29669914}, issn = {1091-6490}, mesh = {Aging ; Humans ; *Immunologic Deficiency Syndromes ; *Neoplasms ; Thymus Gland ; }, } @article {pmid29669913, year = {2018}, author = {Rosenthal, GG and Schumer, M and Andolfatto, P}, title = {How the manakin got its crown: A novel trait that is unlikely to cause speciation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4144-E4145}, pmid = {29669913}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Genetic Speciation ; *Passeriformes ; *Phenotype ; }, } @article {pmid29669603, year = {2018}, author = {Gaulin, E and Pel, MJC and Camborde, L and San-Clemente, H and Courbier, S and Dupouy, MA and Lengellé, J and Veyssiere, M and Le Ru, A and Grandjean, F and Cordaux, R and Moumen, B and Gilbert, C and Cano, LM and Aury, JM and Guy, J and Wincker, P and Bouchez, O and Klopp, C and Dumas, B}, title = {Genomics analysis of Aphanomyces spp. identifies a new class of oomycete effector associated with host adaptation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {43}, pmid = {29669603}, issn = {1741-7007}, abstract = {BACKGROUND: Oomycetes are a group of filamentous eukaryotic microorganisms that have colonized all terrestrial and oceanic ecosystems, and they include prominent plant pathogens. The Aphanomyces genus is unique in its ability to infect both plant and animal species, and as such exemplifies oomycete versatility in adapting to different hosts and environments. Dissecting the underpinnings of oomycete diversity provides insights into their specificity and pathogenic mechanisms.

RESULTS: By carrying out genomic analyses of the plant pathogen A. euteiches and the crustacean pathogen A. astaci, we show that host specialization is correlated with specialized secretomes that are adapted to the deconstruction of the plant cell wall in A. euteiches and protein degradation in A. astaci. The A. euteiches genome is characterized by a large repertoire of small secreted protein (SSP)-encoding genes that are highly induced during plant infection, and are not detected in other oomycetes. Functional analysis revealed an SSP from A. euteiches containing a predicted nuclear-localization signal which shuttles to the plant nucleus and increases plant susceptibility to infection.

CONCLUSION: Collectively, our results show that Aphanomyces host adaptation is associated with evolution of specialized secretomes and identify SSPs as a new class of putative oomycete effectors.}, } @article {pmid29669589, year = {2018}, author = {Coelho, LP and Kultima, JR and Costea, PI and Fournier, C and Pan, Y and Czarnecki-Maulden, G and Hayward, MR and Forslund, SK and Schmidt, TSB and Descombes, P and Jackson, JR and Li, Q and Bork, P}, title = {Similarity of the dog and human gut microbiomes in gene content and response to diet.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {72}, pmid = {29669589}, issn = {2049-2618}, support = {686070//Horizon 2020 Framework Programme (BE)/International ; }, mesh = {Animals ; *Diet ; Dogs ; Feces/microbiology ; *Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Metagenomics/methods ; Mice ; *Microbiota ; Obesity ; Swine ; }, abstract = {BACKGROUND: Gut microbes influence their hosts in many ways, in particular by modulating the impact of diet. These effects have been studied most extensively in humans and mice. In this work, we used whole genome metagenomics to investigate the relationship between the gut metagenomes of dogs, humans, mice, and pigs.

RESULTS: We present a dog gut microbiome gene catalog containing 1,247,405 genes (based on 129 metagenomes and a total of 1.9 terabasepairs of sequencing data). Based on this catalog and taxonomic abundance profiling, we show that the dog microbiome is closer to the human microbiome than the microbiome of either pigs or mice. To investigate this similarity in terms of response to dietary changes, we report on a randomized intervention with two diets (high-protein/low-carbohydrate vs. lower protein/higher carbohydrate). We show that diet has a large and reproducible effect on the dog microbiome, independent of breed or sex. Moreover, the responses were in agreement with those observed in previous human studies.

CONCLUSIONS: We conclude that findings in dogs may be predictive of human microbiome results. In particular, a novel finding is that overweight or obese dogs experience larger compositional shifts than lean dogs in response to a high-protein diet.}, } @article {pmid29669554, year = {2018}, author = {Ayers, T and Tsukamoto, H and Gühmann, M and Veedin Rajan, VB and Tessmar-Raible, K}, title = {A Go-type opsin mediates the shadow reflex in the annelid Platynereis dumerilii.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {41}, pmid = {29669554}, issn = {1741-7007}, support = {337011//European Research Council/International ; }, abstract = {BACKGROUND: The presence of photoreceptive molecules outside the eye is widespread among animals, yet their functions in the periphery are less well understood. Marine organisms, such as annelid worms, exhibit a 'shadow reflex', a defensive withdrawal behaviour triggered by a decrease in illumination. Herein, we examine the cellular and molecular underpinnings of this response, identifying a role for a photoreceptor molecule of the Go-opsin class in the shadow response of the marine bristle worm Platynereis dumerilii.

RESULTS: We found Pdu-Go-opsin1 expression in single specialised cells located in adult Platynereis head and trunk appendages, known as cirri. Using gene knock-out technology and ablation approaches, we show that the presence of Go-opsin1 and the cirri is necessary for the shadow reflex. Consistently, quantification of the shadow reflex reveals a chromatic dependence upon light of approximately 500 nm in wavelength, matching the photoexcitation characteristics of the Platynereis Go-opsin1. However, the loss of Go-opsin1 does not abolish the shadow reflex completely, suggesting the existence of a compensatory mechanism, possibly acting through a ciliary-type opsin, Pdu-c-opsin2, with a Lambdamax of approximately 490 nm.

CONCLUSIONS: We show that a Go-opsin is necessary for the shadow reflex in a marine annelid, describing a functional example for a peripherally expressed photoreceptor, and suggesting that, in different species, distinct opsins contribute to varying degrees to the shadow reflex.}, } @article {pmid29669552, year = {2018}, author = {Lindenmayer, DB}, title = {Developing accurate prediction systems for the terrestrial environment.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {42}, pmid = {29669552}, issn = {1741-7007}, abstract = {In recent decades, meteorologists have made remarkable progress in predicting the weather, thereby saving lives and considerable sums of money. However, we are way behind when it comes to predicting the effects of environmental change on ecosystems, even when we are ourselves the agent of such change. Given the substantial environmental problems facing our living planet, and the need to tackle these in an ecologically responsible and cost-effective way, we should aspire to develop terrestrial environmental prediction systems that reach the levels of accuracy and precision which characterize weather prediction systems. I argue here that well designed, long-term monitoring programs will be key to developing robust environmental prediction systems.}, } @article {pmid29669537, year = {2018}, author = {Kumaraswamy, A and Kai, K and Ai, H and Ikeno, H and Wachtler, T}, title = {Spatial registration of neuron morphologies based on maximization of volume overlap.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {143}, pmid = {29669537}, issn = {1471-2105}, support = {01GQ1116//BMBF/International ; }, mesh = {*Algorithms ; Animals ; Brain/cytology ; Drosophila melanogaster/*cytology ; Neurons/*cytology ; Principal Component Analysis ; }, abstract = {BACKGROUND: Morphological features are widely used in the study of neuronal function and pathology. Invertebrate neurons are often structurally stereotypical, showing little variance in gross spatial features but larger variance in their fine features. Such variability can be quantified using detailed spatial analysis, which however requires the morphologies to be registered to a common frame of reference.

RESULTS: We outline here new algorithms - Reg-MaxS and Reg-MaxS-N - for co-registering pairs and groups of morphologies, respectively. Reg-MaxS applies a sequence of translation, rotation and scaling transformations, estimating at each step the transformation parameters that maximize spatial overlap between the volumes occupied by the morphologies. We test this algorithm with synthetic morphologies, showing that it can account for a wide range of transformation differences and is robust to noise. Reg-MaxS-N co-registers groups of more than two morphologies by iteratively calculating an average volume and registering all morphologies to this average using Reg-MaxS. We test Reg-MaxS-N using five groups of morphologies from the Droshophila melanogaster brain and identify the cases for which it outperforms existing algorithms and produce morphologies very similar to those obtained from registration to a standard brain atlas.

CONCLUSIONS: We have described and tested algorithms for co-registering pairs and groups of neuron morphologies. We have demonstrated their application to spatial comparison of stereotypic morphologies and calculation of dendritic density profiles, showing how our algorithms for registering neuron morphologies can enable new approaches in comparative morphological analyses and visualization.}, } @article {pmid29669519, year = {2018}, author = {Deng, L and Li, W and Zhong, Z and Chai, Y and Yang, L and Zheng, H and Wang, W and Fu, H and He, M and Huang, X and Zuo, Z and Wang, Y and Cao, S and Liu, H and Ma, X and Wu, K and Peng, G}, title = {Molecular characterization and new genotypes of Enterocytozoon bieneusi in pet chipmunks (Eutamias asiaticus) in Sichuan province, China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {37}, pmid = {29669519}, issn = {1471-2180}, abstract = {BACKGROUND: Enterocytozoon bieneusi, the most commonly identified microsporidian species in humans, is also identified in livestock, birds, rodents, reptiles, companion animals, even wastewater. However, there is no information available on occurrence of E. bieneusi in pet chipmunks. The aim of the present study was to determine the genotypes, molecular characterization of E. bieneusi in pet chipmunks, and assess the zoonotic potential.

RESULTS: A total of 279 fecal specimens were collected from chipmunks from seven pet shops and one breeding facility in Sichuan province, China. The prevalence for E. bieneusi was 17.6% (49/279) based on nested PCR targeting the internal transcribed spacer (ITS) region. The prevalence of E. bieneusi in chipmunks < 90 days of age was significantly higher than that in older chipmunks; however, differences among different sources and between genders were not significant. Eight genotypes of E. bieneusi were identified, including four known genotypes (D, Nig7, CHG9, and CHY1) and four novel genotypes (SCC-1 to 4). Phylogenetic analysis classified these genotypes into four distinct groups as follows: genotypes D and CHG9 clustered into group 1 of zoonotic potential; genotypes Nig7 and CHY1 clustered into group 6 and a new group, respectively; the four novel genotypes (SCC-1 to 4) formed a separate group named group 10.

CONCLUSIONS: To the best of our knowledge, this is the first study reporting the prevalence and genotypes of E. bieneusi in pet chipmunks in China. Genotypes D and Nig7, found in chipmunks in this study, have also been previously identified in humans, which suggests that chipmunks might play a role in the transmission of this pathogen to humans.}, } @article {pmid29669518, year = {2018}, author = {Maramis, C and Gkoufas, A and Vardi, A and Stalika, E and Stamatopoulos, K and Hatzidimitriou, A and Maglaveras, N and Chouvarda, I}, title = {IRProfiler - a software toolbox for high throughput immune receptor profiling.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {144}, pmid = {29669518}, issn = {1471-2105}, support = {644906//Horizon 2020 Framework Programme (BE)/International ; }, mesh = {Algorithms ; Hematologic Diseases/diagnosis/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Receptors, Antigen, B-Cell/*genetics/immunology ; Receptors, Antigen, T-Cell/*genetics/immunology ; Sequence Analysis, DNA ; *Software ; }, abstract = {BACKGROUND: The study of the huge diversity of immune receptors, often referred to as immune repertoire profiling, is a prerequisite for diagnosis, prognostication and monitoring of hematological disorders. In the era of high-throughput sequencing (HTS), the abundance of immunogenetic data has revealed unprecedented opportunities for the thorough profiling of T-cell receptors (TR) and B-cell receptors (BcR). However, the volume of the data to be analyzed mandates for efficient and ease-to-use immune repertoire profiling software applications.

RESULTS: This work introduces Immune Repertoire Profiler (IRProfiler), a novel software pipeline that delivers a number of core receptor repertoire quantification and comparison functionalities on high-throughput TR and BcR sequencing data. Adopting 5 alternative clonotype definitions, IRProfiler implements a series of algorithms for 1) data filtering, 2) calculation of clonotype diversity and expression, 3) calculation of gene usage for the V and J subgroups, 4) detection of shared and exclusive clonotypes among multiple repertoires, and 5) comparison of gene usage for V and J subgroups among multiple repertoires. IRProfiler has been implemented as a toolbox of the Galaxy bioinformatics platform, comprising 6 tools. Theoretical and experimental evaluation has shown that the tools of IRProfiler are able to scale well with respect to the size of input dataset(s). IRProfiler has been utilized by a number of recently published studies concerning hematological disorders.

CONCLUSION: IRProfiler is made freely available via 3 distribution channels, including the Galaxy Tool Shed. Despite being a new entry in a crowded ecosystem of immune repertoire profiling software, IRProfiler founds its added value on its support for alternative clonotype definitions in conjunction with a combination of properties stemming from its user-centric design, namely ease-of-use, ease-of-access, exploitability of the output data, and analysis flexibility.}, } @article {pmid29669517, year = {2018}, author = {Orsucci, M and Audiot, P and Dorkeld, F and Pommier, A and Vabre, M and Gschloessl, B and Rialle, S and Severac, D and Bourguet, D and Streiff, R}, title = {Larval transcriptomic response to host plants in two related phytophagous lepidopteran species: implications for host specialization and species divergence.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {265}, pmid = {29669517}, issn = {1471-2164}, support = {ANR-13-BSV7-0012-01//Agence Nationale de la Recherche (FR)/ ; }, mesh = {*Adaptation, Physiological ; Animals ; *Artemisia ; Evolution, Molecular ; Feeding Behavior/*physiology ; *Host Specificity ; Larva/*genetics/physiology ; Lepidoptera/*genetics/physiology ; Molecular Sequence Annotation ; *Transcriptome ; *Zea mays ; }, abstract = {BACKGROUND: Most phytophagous insects have morphological, behavioral and physiological adaptations allowing them to specialize on one or a few plant species. Identifying the mechanisms involved in host plant specialization is crucial to understand the role of divergent selection between different environments in species diversification, and to identify sustainable targets for the management of insect pest species. In the present study, we measured larval phenotypic and transcriptomic responses to host plants in two related phytophagous lepidopteran species: the European corn borer (ECB), a worldwide pest of maize, and the adzuki bean borer (ABB), which feeds of various dicotyledons. Our aim was to identify the genes and functions underlying host specialization and/or divergence between ECB and ABB.

RESULTS: At the phenotypic level, we observed contrasted patterns of survival, weight gain and developmental time between ECB and ABB, and within ECB and ABB reared on two different host plants. At the transcriptomic level, around 8% of the genes were differentially expressed (DE) between species and/or host plant. 70% of these DE genes displayed a divergent pattern of expression between ECB and ABB, regardless of the host, while the remaining 30% were involved in the plastic response between hosts. We further categorized plastic DE genes according to their parallel or opposite pattern between ECB and ABB to specifically identify candidate genes involved in the species divergence by host specialization. These candidates highlighted a comprehensive response, involving functions related to plant recognition, digestion, detoxification, immunity and development. Last, we detected viral, bacterial, and yeast genes whose incidence contrasted ECB and ABB samples, and maize and mugwort conditions. We suggest that these microorganism communities might influence the survival, metabolism and defense patterns observed in ECB and ABB larvae.

CONCLUSIONS: The comprehensive approach developed in the present study allowed to identify phenotypic specialization patterns and underlying candidate molecular mechanisms, and highlighted the putative role of microorganisms in the insect-host plant interaction. These findings offer the opportunity to pinpoint specific and sustainable molecular or physiological targets for the regulation of ECB pest populations.}, } @article {pmid29669516, year = {2018}, author = {Lupino, KM and Romano, KA and Simons, MJ and Gregg, JT and Panepinto, L and Cruz, GM and Grajek, L and Caputo, GA and Hickman, MJ and Hecht, GB}, title = {A Recurrent Silent Mutation Implicates fecA in Ethanol Tolerance by Escherichia coli.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {36}, pmid = {29669516}, issn = {1471-2180}, abstract = {BACKGROUND: An issue associated with efficient bioethanol production is the fact that the desired product is toxic to the biocatalyst. Among other effects, ethanol has previously been found to influence the membrane of E. coli in a dose-dependent manner and induce changes in the lipid composition of the plasma membrane. We describe here the characterization of a collection of ethanol-tolerant strains derived from the ethanologenic Escherichia coli strain FBR5.

RESULTS: Membrane permeability assays indicate that many of the strains in the collection have alterations in membrane permeability and/or responsiveness of the membrane to environmental changes such as temperature shifts or ethanol exposure. However, analysis of the strains by gas chromatography and mass spectrometry revealed no qualitative changes in the acyl chain composition of membrane lipids in response to ethanol or temperature. To determine whether these strains contain any mutations that might contribute to ethanol tolerance or changes in membrane permeability, we sequenced the entire genome of each strain. Unexpectedly, none of the strains displayed mutations in genes known to control membrane lipid synthesis, and a few strains carried no mutations at all. Interestingly, we found that four independently-isolated strains acquired an identical C → A (V244 V) silent mutation in the ferric citrate transporter gene fecA. Further, we demonstrated that either a deletion of fecA or over-expression of fecA can confer increased ethanol survival, suggesting that any misregulation of fecA expression affects the cellular response to ethanol.

CONCLUSIONS: The fact that no mutations were observed in several ethanol-tolerant strains suggested that epigenetic mechanisms play a role in E. coli ethanol tolerance and membrane permeability. Our data also represent the first direct phenotypic evidence that the fecA gene plays a role in ethanol tolerance. We propose that the recurring silent mutation may exert an effect on phenotype by altering RNA-mediated regulation of fecA expression.}, } @article {pmid29669515, year = {2018}, author = {Yang, H and Li, T and Dang, K and Bu, W}, title = {Compositional and mutational rate heterogeneity in mitochondrial genomes and its effect on the phylogenetic inferences of Cimicomorpha (Hemiptera: Heteroptera).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {264}, pmid = {29669515}, issn = {1471-2164}, support = {31430079//National Natural Science Foundation of China/ ; 31372240//National Natural Science Foundation of China/ ; 31501879//National Natural Science Foundation of China/ ; No. 2012FY111100//the Subject of Scientific and Technological Basic Work/ ; }, mesh = {Animals ; Evolution, Molecular ; Genome, Insect/genetics ; Genome, Mitochondrial/*genetics ; Heteroptera/*classification/*genetics ; *Mutation Rate ; *Phylogeny ; }, abstract = {BACKGROUND: Mitochondrial genome (mt-genome) data can potentially return artefactual relationships in the higher-level phylogenetic inference of insects due to the biases of accelerated substitution rates and compositional heterogeneity. Previous studies based on mt-genome data alone showed a paraphyly of Cimicomorpha (Insecta, Hemiptera) due to the positions of the families Tingidae and Reduviidae rather than the monophyly that was supported based on morphological characters, morphological and molecular combined data and large scale molecular datasets. Various strategies have been proposed to ameliorate the effects of potential mt-genome biases, including dense taxon sampling, removal of third codon positions or purine-pyrimidine coding and the use of site-heterogeneous models. In this study, we sequenced the mt-genomes of five additional Tingidae species and discussed the compositional and mutational rate heterogeneity in mt-genomes and its effect on the phylogenetic inferences of Cimicomorpha by implementing the bias-reduction strategies mentioned above.

RESULTS: Heterogeneity in nucleotide composition and mutational biases were found in mt protein-coding genes, and the third codon exhibited high levels of saturation. Dense taxon sampling of Tingidae and Reduviidae and the other common strategies mentioned above were insufficient to recover the monophyly of the well-established group Cimicomorpha. When the sites with weak phylogenetic signals in the dataset were removed, the remaining dataset of mt-genomes can support the monophyly of Cimicomorpha; this support demonstrates that mt-genomes possess strong phylogenetic signals for the inference of higher-level phylogeny of this group. Comparison of the ratio of the removal of amino acids for each PCG showed that ATP8 has the highest ratio while CO1 has the lowest. This pattern is largely congruent with the evolutionary rate of 13 PCGs that ATP8 represents the highest evolutionary rate, whereas CO1 appears to be the lowest. Notably, the value of Ka/Ks ratios of all PCGs is less than 1, indicating that these genes are likely evolving under purifying selection.

CONCLUSIONS: Our results demonstrate that mt-genomes have sites with strong phylogenetic signals for the inference of higher-level phylogeny of Cimicomorpha. Consequently, bioinformatic approaches to removing sites with weak phylogenetic signals in mt-genome without relying on an a priori tree topology would greatly improve this field.}, } @article {pmid29669514, year = {2018}, author = {Gasperotti, AF and Revuelta, MV and Studdert, CA and Herrera Seitz, MK}, title = {Identification of two different chemosensory pathways in representatives of the genus Halomonas.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {266}, pmid = {29669514}, issn = {1471-2164}, support = {PIP 0607 to Herrera Seitz and Studdert//CONICET/ ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/chemistry/genetics/*metabolism ; Chemotaxis ; Halomonas/*cytology/genetics/*metabolism ; Models, Molecular ; Phylogeny ; Protein Conformation ; }, abstract = {BACKGROUND: Species of the genus Halomonas are salt-tolerant organisms that have a versatile metabolism and can degrade a variety of xenobiotic compounds, utilizing them as their sole carbon source. In this study, we examined the genome of a Halomonas isolate from a hydrocarbon-contaminated site to search for chemosensory genes that might be responsible for the observed chemotactic behavior of this organism as well as for other responses to environmental cues.

RESULTS: Using genome-wide comparative tools, our isolate was identified as a strain of Halomonas titanicae (strain KHS3), together with two other Halomonas strains with available genomes that had not been previously identified at a species level. The search for the main components of chemosensory pathways resulted in the identification of two clusters of chemosensory genes and a total of twenty-five chemoreceptor genes. One of the gene clusters is very similar to the che cluster from Escherichia coli and, presumably, it is responsible for the chemotactic behavior towards a variety of compounds. This gene cluster is present in 47 out of 56 analyzed Halomonas strains with available genomes. A second che-like cluster includes a gene coding for a diguanylate cyclase with a phosphotransfer and two receiver domains, as well as a gene coding for a chemoreceptor with a longer cytoplasmic domain than the other twenty-four. This seemingly independent pathway resembles the wsp pathway from Pseudomonas aeruginosa although it also presents several differences in gene order and domain composition. This second chemosensory gene cluster is only present in a sub-group within the genus Halomonas. Moreover, remarkably similar gene clusters are also found in some orders of Proteobacteria phylogenetically more distant from the Oceanospirillales, suggesting the occurrence of lateral transfer events.

CONCLUSIONS: Chemosensory pathways were investigated within the genus Halomonas. A canonical chemotaxis pathway, controlled by a variable number of chemoreceptors, is widespread among Halomonas species. A second chemosensory pathway of unique organization that involves some type of c-di-GMP signaling was found to be present only in one branch of the genus, as well as in other proteobacterial lineages.}, } @article {pmid29669513, year = {2018}, author = {Lee, JR and Ryu, DS and Park, SJ and Choe, SH and Cho, HM and Lee, SR and Kim, SU and Kim, YH and Huh, JW}, title = {Successful application of human-based methyl capture sequencing for methylome analysis in non-human primate models.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {267}, pmid = {29669513}, issn = {1471-2164}, support = {KGM4241743//Korea Research Institute of Bioscience and Biotechnology/ ; KGM4611714//Korea Research Institute of Bioscience and Biotechnology/ ; NRF-2014M3A9B6070243//National Research Foundation of Korea/ ; }, mesh = {Animals ; *Cercopithecus aethiops ; *DNA Methylation ; Epigenomics/*methods ; Genome, Human/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; *Macaca fascicularis ; Promoter Regions, Genetic/genetics ; Sequence Analysis, DNA ; Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: The characterization of genomic or epigenomic variation in human and animal models could provide important insight into pathophysiological mechanisms of various diseases, and lead to new developments in disease diagnosis and clinical intervention. The African green monkey (AGM; Chlorocebus aethiops) and cynomolgus monkey (CM; Macaca fascicularis) have long been considered important animal models in biomedical research. However, non-human primate-specific methods applicable to epigenomic analyses in AGM and CM are lacking. The recent development of methyl-capture sequencing (MC-seq) has an unprecedented advantage of cost-effectiveness, and further allows for extending the methylome coverage compared to conventional sequencing approaches.

RESULTS: Here, we used a human probe-designed MC-seq method to assay DNA methylation in DNA obtained from 13 CM and three AGM blood samples. To effectively adapt the human probe-designed target region for methylome analysis in non-human primates, we redefined the target regions, focusing on regulatory regions and intragenic regions with consideration of interspecific sequence homology and promoter region variation. Methyl-capture efficiency was controlled by the sequence identity between the captured probes based on the human reference genome and the AGM and CM genome sequences, respectively. Using reasonable guidelines, 56 and 62% of the human-based capture probes could be effectively mapped for DNA methylome profiling in the AGM and CM genome, respectively, according to numeric global statistics. In particular, our method could cover up to 89 and 87% of the regulatory regions of the AGM and CM genome, respectively.

CONCLUSIONS: Use of human-based MC-seq methods provides an attractive, cost-effective approach for the methylome profiling of non-human primates at the single-base resolution level.}, } @article {pmid29669511, year = {2018}, author = {LaVoie, SP and Summers, AO}, title = {Correction to: Transcriptional responses of Escherichia coli during recovery from inorganic or organic mercury exposure.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {268}, pmid = {29669511}, issn = {1471-2164}, abstract = {After publication of the original article [1] the authors noted that the key displayed in Figure 1a was incorrect, as the PMA and HgCl2 conditions had been switched.}, } @article {pmid29669130, year = {2018}, author = {Sarangi, GK and Romagné, F and Castellano, S}, title = {Distinct Patterns of Selection in Selenium-Dependent Genes between Land and Aquatic Vertebrates.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1744-1756}, doi = {10.1093/molbev/msy070}, pmid = {29669130}, issn = {1537-1719}, abstract = {Selenium (Se), a sparse element on earth, is an essential micronutrient in the vertebrate diet and its intake depends on its content in soils and waters worldwide. Selenium is required due to its function in selenoproteins, which contain selenocysteine (Sec), the 21st amino acid in the genetic code, as one of their constituent residues. Selenocysteine is analogous to the amino acid cysteine (Cys), which uses the abounding element sulfur instead. Despite the irregular distribution of Se worldwide, its distinct biochemical properties have made the substitution of Sec for Cys rare in vertebrate proteins. Still, vertebrates inhabited environments with different amounts of Se and may have distinctly adapted to it. To address this question, we compared the evolutionary forces acting on the coding sequences of selenoprotein genes and genes that regulate Se between vertebrate clades and between the Se-dependent genes and their paralogs with Cys. We find that the strength of natural selection in genes that use or regulate Se is distinct between land vertebrates and teleost fishes and more variable than in the Cys paralogs, particularly in genes involved in the preferential supply of Se to some organs and the tissue-specific expression of selenoproteins. This is compatible with vertebrates adapting to Se scarcity in land and its abundance in waters. In agreement, teleost fishes duplicated and subfunctionalized or neofunctionalized selenoprotein genes and maintained their capacity for Se transport in the body, which declined (under neutrality) for millions of years in terrestrial vertebrates. Dietary Se has thus distinctly shaped vertebrate evolution.}, } @article {pmid29669107, year = {2018}, author = {Xia, X}, title = {DAMBE7: New and Improved Tools for Data Analysis in Molecular Biology and Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1550-1552}, pmid = {29669107}, issn = {1537-1719}, abstract = {DAMBE is a comprehensive software package for genomic and phylogenetic data analysis on Windows, Linux, and Macintosh computers. New functions include imputing missing distances and phylogeny simultaneously (paving the way to build large phage and transposon trees), new bootstrapping/jackknifing methods for PhyPA (phylogenetics from pairwise alignments), and an improved function for fast and accurate estimation of the shape parameter of the gamma distribution for fitting rate heterogeneity over sites. Previous method corrects multiple hits for each site independently. DAMBE's new method uses all sites simultaneously for correction. DAMBE, featuring a user-friendly graphic interface, is freely available from http://dambe.bio.uottawa.ca (last accessed, April 17, 2018).}, } @article {pmid29669008, year = {2018}, author = {Yoder, AD and Poelstra, JW and Tiley, GP and Williams, RC}, title = {Neutral Theory Is the Foundation of Conservation Genetics.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1322-1326}, doi = {10.1093/molbev/msy076}, pmid = {29669008}, issn = {1537-1719}, abstract = {Kimura's neutral theory of molecular evolution has been essential to virtually every advance in evolutionary genetics, and by extension, is foundational to the field of conservation genetics. Conservation genetics utilizes the key concepts of neutral theory to identify species and populations at risk of losing evolutionary potential by detecting patterns of inbreeding depression and low effective population size. In turn, this information can inform the management of organisms and their habitat providing hope for the long-term preservation of both. We expand upon Avise's "inventorial" and "functional" categories of conservation genetics by proposing a third category that is linked to the coalescent and that we refer to as "process-driven." It is here that connections between Kimura's theory and conservation genetics are strongest. Process-driven conservation genetics can be especially applied to large genomic data sets to identify patterns of historical risk, such as population bottlenecks, and accordingly, yield informed intuitions for future outcomes. By examining inventorial, functional, and process-driven conservation genetics in sequence, we assess the progression from theory, to data collection and analysis, and ultimately, to the production of hypotheses that can inform conservation policies.}, } @article {pmid29668970, year = {2018}, author = {Sato, Y and Miya, M and Fukunaga, T and Sado, T and Iwasaki, W}, title = {MitoFish and MiFish Pipeline: A Mitochondrial Genome Database of Fish with an Analysis Pipeline for Environmental DNA Metabarcoding.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1553-1555}, pmid = {29668970}, issn = {1537-1719}, abstract = {Fish mitochondrial genome (mitogenome) data form a fundamental basis for revealing vertebrate evolution and hydrosphere ecology. Here, we report recent functional updates of MitoFish, which is a database of fish mitogenomes with a precise annotation pipeline MitoAnnotator. Most importantly, we describe implementation of MiFish pipeline for metabarcoding analysis of fish mitochondrial environmental DNA, which is a fast-emerging and powerful technology in fish studies. MitoFish, MitoAnnotator, and MiFish pipeline constitute a key platform for studies of fish evolution, ecology, and conservation, and are freely available at http://mitofish.aori.u-tokyo.ac.jp/ (last accessed April 7th, 2018).}, } @article {pmid29668953, year = {2018}, author = {Ausiannikava, D and Mitchell, L and Marriott, H and Smith, V and Hawkins, M and Makarova, KS and Koonin, EV and Nieduszynski, CA and Allers, T}, title = {Evolution of Genome Architecture in Archaea: Spontaneous Generation of a New Chromosome in Haloferax volcanii.}, journal = {Molecular biology and evolution}, volume = {35}, number = {8}, pages = {1855-1868}, pmid = {29668953}, issn = {1537-1719}, abstract = {The common ancestry of archaea and eukaryotes is evident in their genome architecture. All eukaryotic and several archaeal genomes consist of multiple chromosomes, each replicated from multiple origins. Three scenarios have been proposed for the evolution of this genome architecture: 1) mutational diversification of a multi-copy chromosome; 2) capture of a new chromosome by horizontal transfer; 3) acquisition of new origins and splitting into two replication-competent chromosomes. We report an example of the third scenario: the multi-origin chromosome of the archaeon Haloferax volcanii has split into two elements via homologous recombination. The newly generated elements are bona fide chromosomes, because each bears "chromosomal" replication origins, rRNA loci, and essential genes. The new chromosomes were stable during routine growth but additional genetic manipulation, which involves selective bottlenecks, provoked further rearrangements. To the best of our knowledge, rearrangement of a naturally evolved prokaryotic genome to generate two new chromosomes has not been described previously.}, } @article {pmid29668933, year = {2018}, author = {Roberts, MC and Joshi, PR and Greninger, AL and Melendez, D and Paudel, S and Acharya, M and Bimali, NK and Koju, NP and No, D and Chalise, M and Kyes, RC}, title = {The human clone ST22 SCCmec IV methicillin-resistant Staphylococcus aureus isolated from swine herds and wild primates in Nepal: is man the common source?.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, pmid = {29668933}, issn = {1574-6941}, abstract = {Swine nasal samples [n = 282] were collected from 12 randomly selected farms around Kathmandu, Nepal, from healthy animals. In addition, wild monkey (Macaca mulatta) saliva samples [n = 59] were collected near temples areas in Kathmandu using a non-invasive sampling technique. All samples were processed for MRSA using standardized selective media and conventional biochemical tests. MRSA verification was done and isolates characterized by SCCmec, multilocus sequence typing, whole genome sequencing [WGS] and antibiotic susceptibilities. Six (2.1%) swine MRSA were isolated from five of the different swine herds tested, five were ST22 type IV and one ST88 type V. Four (6.8%) macaques MRSA were isolated, with three ST22 SCCmec type IV and one ST239 type III. WGS sequencing showed that the eight ciprofloxacin resistant ST22 isolates carried gyrA mutation [S84L]. Six isolates carried the erm(C) genes, five isolates carried aacC-aphD genes and four isolates carried blaZ genes. The swine linezolid resistant ST22 did not carry any known acquired linezolid resistance genes but had a mutation in ribosomal protein L22 [A29V] and an insertion in L4 [68KG69], both previously associated with linezolid resistance. Multiple virulence factors were also identified. This is the first time MRSA ST22 SCCmec IV has been isolated from livestock or primates.}, } @article {pmid29668932, year = {2018}, author = {Grosdidier, M and Ioos, R and Husson, C and Cael, O and Scordia, T and Marçais, B}, title = {Tracking the invasion: dispersal of Hymenoscyphus fraxineus airborne inoculum at different scales.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy049}, pmid = {29668932}, issn = {1574-6941}, abstract = {Ash dieback is caused by an invasive pathogen Hymenoscyphus fraxineus, which emerged in Europe in the 1990s and jeopardizes the management of ash stands. Although the biological cycle of the pathogen is well understood, its dispersal patterns via airborne spores remain poorly described. We investigated the seasonal and spatial patterns of dispersal in France using both a passive spore-trapping method coupled with a real-time PCR assay and reports of ash dieback based on symptom observations. Spores detection varies from year to year with a detection ability of 30-47% depending on meteorological conditions, which affect both production of inoculum and efficiency of the trapping. Nevertheless, our results are consistent and we showed that the sporulation peak occurred from June to August and that spores were detected up to 50-100 km ahead of the disease front, proving the presence of the pathogen before any observation of symptoms. The spore dispersal gradient was steep, most of inoculum remaining within 50 m of infected ashes. Two dispersal kernels were fitted using Bayesian methods to estimate the mean dispersal distance of H. fraxineus from inoculum sources. The estimated mean distances of dispersal, either local or regional scale, were 1.4 km and 2.6 km, respectively, the best fitting kernel being the inverse power-law. This information may help to design disease management strategies.}, } @article {pmid29668923, year = {2018}, author = {Lund, MB and Mogensen, MF and Marshall, IPG and Albertsen, M and Viana, F and Schramm, A}, title = {Genomic insights into the Agromyces-like symbiont of earthworms and its distribution among host species.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy068}, pmid = {29668923}, issn = {1574-6941}, abstract = {The nephridia (excretory organs) of lumbricid earthworms generally harbor symbiotic bacteria. In the compost worms Eisenia fetida and E. andrei, these comprise Verminephrobacter, Ca. Nephrothrix and an Agromyces-like symbiont. While diversity, transmission, and function of the first two symbionts has been unraveled in recent years, little is known about the biology of the uncultured Agromyces-like symbiont or about its distribution within lumbricid earthworms.In this study, we sequenced a cocoon metagenome of E. andrei and assembled a 96.3% complete genome of the Agromyces-like symbiont, which indicates a heterotrophic and potentially microaerophilic lifestyle. A 16S rRNA gene based survey showed that the Agromyces-like symbiont has a narrow host range (present in 10 out of 51 investigated lumbricid earthworm species) and is likely species-specific or at least specific for groups of closely related host species. The Agromyces-like symbionts form a monophyletic group and feature a reduced genome with AT-bias and very low genome-wide similarity to closely related Agromyces spp. (average amino acid identity of 64%); therefore, we suggest establishing a novel genus for the Agromyces-like symbionts of earthworms, for which we propose the name Candidatus Lumbricidophila, with the specific symbiont of Eisenia andrei as novel species Ca. L. eiseniae.}, } @article {pmid29668898, year = {2018}, author = {Molina, V and Dorador, C and Fernández, C and Bristow, L and Eissler, Y and Hengst, M and Hernandez, K and Olsen, LM and Harrod, C and Marchant, F and Anguita, C and Cornejo, M}, title = {The activity of nitrifying microorganisms in a high-altitude Andean wetland.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy062}, pmid = {29668898}, issn = {1574-6941}, abstract = {High-altitude wetland holds freshwater springs, evaporitic ponds and lagoon with variable salinity and nutrients, potentially influencing the ecology of nitrifying communities. In this study, nitrifying microorganisms in Salar de Huasco (Chile) were surveyed to determine bacterial and archaeal contribution to ammonium (AO), nitrite oxidation (NO), ammonium uptake (AU) during wet and dry seasons. The activity signals from these groups were assessed by specific amoA-qPCR transcription, 15N tracer studies and addition of group specific inhibitor experiments for nitrifying microorganisms (N1-guanyl-1, 7-diaminoheptane [GC7]-archaeal specific and allylthiourea [ATU]-bacterial specific). Nitrifying communities, i.e. Nitrosopumilus, Nitrosospira, Nitrosomonas, Kuenenia and Nitrospira, were more frequent (∼0.25% of 16S rRNA sequences) at low salinity sites. Bacterial amoA-qPCR transcripts also increased at low salinity and along in situ ammonium increase observed between wet/dry seasons. Nutrient changes through time and 15N tracer experiments results showed that AO and NO were detected and peaked mainly at low salinity-high ammonium sites (<37 000 μS cm-1 and >0.3 μM), whereas AU was predominant at evaporitic sites. Our results indicate that salinity and ammonium affect the nitrifying communities that are potentially more active at low-salinity sites but persistent at saltier evaporitic areas of the wetland when ammonium is available.}, } @article {pmid29668882, year = {2018}, author = {Kharbush, JJ and Thompson, LR and Haroon, MF and Knight, R and Aluwihare, LI}, title = {Hopanoid-producing bacteria in the Red Sea include the major marine nitrite oxidizers.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy063}, pmid = {29668882}, issn = {1574-6941}, abstract = {Hopanoids, including the extended side chain-containing bacteriohopanepolyols, are bacterial lipids found abundantly in the geological record and across Earth's surface environments. However, the physiological roles of this biomarker remain uncertain, limiting interpretation of their presence in current and past environments. Recent work investigating the diversity and distribution of hopanoid producers in the marine environment implicated low-oxygen regions as important loci of hopanoid production, and data from marine oxygen minimum zones suggested that the dominant hopanoid producers in these environments are nitrite-utilizing organisms, revealing a potential connection between hopanoid production and the marine nitrogen cycle. Here, we use metagenomic data from the Red Sea to investigate the ecology of hopanoid producers in an environmental setting that is biogeochemically distinct from those investigated previously. The distributions of hopanoid production and nitrite oxidation genes in the Red Sea are closely correlated, and the majority of hopanoid producers are taxonomically affiliated with the major marine nitrite oxidizers, Nitrospinae and Nitrospirae. These results suggest that the relationship between hopanoid production and nitrite oxidation is conserved across varying biogeochemical conditions in dark ocean microbial ecosystems.}, } @article {pmid29668306, year = {2018}, author = {Samata, M and Akhtar, A}, title = {Dosage Compensation of the X Chromosome: A Complex Epigenetic Assignment Involving Chromatin Regulators and Long Noncoding RNAs.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {323-350}, doi = {10.1146/annurev-biochem-062917-011816}, pmid = {29668306}, issn = {1545-4509}, abstract = {X chromosome regulation represents a prime example of an epigenetic phenomenon where coordinated regulation of a whole chromosome is required. In flies, this is achieved by transcriptional upregulation of X chromosomal genes in males to equalize the gene dosage differences in females. Chromatin-bound proteins and long noncoding RNAs (lncRNAs) constituting a ribonucleoprotein complex known as the male-specific lethal (MSL) complex or the dosage compensation complex mediate this process. MSL complex members decorate the male X chromosome, and their absence leads to male lethality. The male X chromosome is also enriched with histone H4 lysine 16 acetylation (H4K16ac), indicating that the chromatin compaction status of the X chromosome also plays an important role in transcriptional activation. How the X chromosome is specifically targeted and how dosage compensation is mechanistically achieved are central questions for the field. Here, we review recent advances, which reveal a complex interplay among lncRNAs, the chromatin landscape, transcription, and chromosome conformation that fine-tune X chromosome gene expression.}, } @article {pmid29668305, year = {2018}, author = {Kenney, GE and Rosenzweig, AC}, title = {Chalkophores.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {645-676}, pmid = {29668305}, issn = {1545-4509}, support = {R35 GM118035/GM/NIGMS NIH HHS/United States ; }, abstract = {Copper-binding metallophores, or chalkophores, play a role in microbial copper homeostasis that is analogous to that of siderophores in iron homeostasis. The best-studied chalkophores are members of the methanobactin (Mbn) family-ribosomally produced, posttranslationally modified natural products first identified as copper chelators responsible for copper uptake in methane-oxidizing bacteria. To date, Mbns have been characterized exclusively in those species, but there is genomic evidence for their production in a much wider range of bacteria. This review addresses the current state of knowledge regarding the function, biosynthesis, transport, and regulation of Mbns. While the roles of several proteins in these processes are supported by substantial genetic and biochemical evidence, key aspects of Mbn manufacture, handling, and regulation remain unclear. In addition, other natural products that have been proposed to mediate copper uptake as well as metallophores that have biologically relevant roles involving copper binding, but not copper uptake, are discussed.}, } @article {pmid29668109, year = {2018}, author = {Kamiya, T and Mideo, N and Alizon, S}, title = {Coevolution of virulence and immunosuppression in multiple infections.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {995-1005}, doi = {10.1111/jeb.13280}, pmid = {29668109}, issn = {1420-9101}, abstract = {Many components of host-parasite interactions have been shown to affect the way virulence (i.e. parasite-induced harm to the host) evolves. However, coevolution of multiple parasite traits is often neglected. We explore how an immunosuppressive adaptation of parasites affects and coevolves with virulence in multiple infections. Applying the adaptive dynamics framework to epidemiological models with coinfection, we show that immunosuppression is a double-edged sword for the evolution of virulence. On one hand, it amplifies the adaptive benefit of virulence by increasing the abundance of coinfections through epidemiological feedbacks. On the other hand, immunosuppression hinders host recovery, prolonging the duration of infection and elevating the cost of killing the host (as more opportunities for transmission will be forgone if the host dies). The balance between the cost and benefit of immunosuppression varies across different background mortality rates of hosts. In addition, we find that immunosuppression evolution is influenced considerably by the precise trade-off shape determining the effect of immunosuppression on host recovery and susceptibility to further infection. These results demonstrate that the evolution of virulence is shaped by immunosuppression while highlighting that the evolution of immune evasion mechanisms deserves further research attention.}, } @article {pmid29667189, year = {2018}, author = {Zajitschek, F and Connallon, T}, title = {Antagonistic pleiotropy in species with separate sexes, and the maintenance of genetic variation in life-history traits and fitness.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1306-1316}, doi = {10.1111/evo.13493}, pmid = {29667189}, issn = {1558-5646}, abstract = {Antagonistic pleiotropy (AP)-where alleles of a gene increase some components of fitness at a cost to others-can generate balancing selection, and contribute to the maintenance of genetic variation in fitness traits, such as survival, fecundity, fertility, and mate competition. Previous theory suggests that AP is unlikely to maintain variation unless antagonistic selection is strong, or AP alleles exhibit pronounced differences in genetic dominance between the affected traits. We show that conditions for balancing selection under AP expand under the likely scenario that the strength of selection on each fitness component differs between the sexes. Our model also predicts that the vast majority of balanced polymorphisms have sexually antagonistic effects on total fitness, despite the absence of sexual antagonism for individual fitness components. We conclude that AP polymorphisms are less difficult to maintain than predicted by prior theory, even under our conservative assumption that selection on components of fitness is universally sexually concordant. We discuss implications for the maintenance of genetic variation, and for inferences of sexual antagonism that are based on sex-specific phenotypic selection estimates-many of which are based on single fitness components.}, } @article {pmid29666939, year = {2018}, author = {Jin, D and Gu, B and Xiong, D and Huang, G and Huang, X and Liu, L and Xiao, J}, title = {A Transcriptomic Analysis of Saccharomyces cerevisiae Under the Stress of 2-Phenylethanol.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1068-1076}, pmid = {29666939}, issn = {1432-0991}, mesh = {Biological Transport/*drug effects ; Gene Expression Profiling ; Membrane Proteins/*biosynthesis ; Phenylethyl Alcohol/*pharmacology ; Saccharomyces cerevisiae/*drug effects/genetics/*growth & development ; Transcriptome/genetics ; }, abstract = {2-Phenylethanol (2-PE) is a kind of advanced aromatic alcohol with rose fragrance, which is wildly used for the deployment of flavors and fragrances. Microbial transformation is the most feasible method for the production of natural 2-PE. But a bottleneck problem is the toxicity of 2-PE on the cells. The molecular mechanisms of the toxic effect of 2-PE to Saccharomyces cerevisiae are not well studied. In this study, we analyzed the transcriptomes of S. cerevisiae in the media with and without 2-PE, respectively, using Illumina RNA-Seq technology. We identified 580 differentially expressed genes between S. cerevisiae in two different treatments. GO and KEGG enrichment analyses of these genes suggested that most genes encoding mitochondrial proteins, cytoplasmic, and plasma membrane proteins were significantly up-regulated, whereas the enzymes related to amino acid metabolism were down-regulated. These results indicated that 2-PE suppressed the synthesis of plasma membrane proteins, which suppressed the transport of nutrients required for growth. The findings in this study will provide insight into the inhibitory mechanism of 2-PE to yeast and other microbes.}, } @article {pmid29666910, year = {2018}, author = {Boyan, GS and Williams, L and Müller, T and Bacon, JP}, title = {Ontogeny and development of the tritocerebral commissure giant (TCG): an identified neuron in the brain of the grasshopper Schistocerca gregaria.}, journal = {Development genes and evolution}, volume = {228}, number = {3-4}, pages = {149-162}, pmid = {29666910}, issn = {1432-041X}, support = {BO 1434/3-5//Deutsche Forschungsgemeinschaft/International ; 313 - ARC - VII 93 / 50//Agricultural Research Council/International ; }, mesh = {Animals ; Brain/growth & development/physiology ; Embryo, Nonmammalian/*cytology/physiology ; Grasshoppers/*cytology/*growth & development/physiology ; Neurons/*cytology/physiology ; }, abstract = {The tritocerebral commissure giant (TCG) of the grasshopper Schistocerca gregaria is one of the best anatomically and physiologically described arthropod brain neurons. A member of the so-called Ventral Giant cluster of cells, it integrates sensory information from visual, antennal and hair receptors, and synapses with thoracic motor neurons in order to initiate and regulate flight behavior. Its ontogeny, however, remains unclear. In this study, we use bromodeoxyuridine incorporation and cyclin labeling to reveal proliferative neuroblasts in the region of the embryonic brain where the ventral giant cluster is located. Engrailed labeling confirms the deutocerebral identity of this cluster. Comparison of soma locations and initial neurite projections into tracts of the striate deutocerebrum help identify the cells of the ventral cluster in both the embryonic and adult brain. Reconstructions of embryonic cell lineages suggest deutocerebral NB1 as being the putative neuroblast of origin. Intracellular dye injection coupled with immunolabeling against neuron-specific horseradish peroxidase is used to identify the VG1 (TCG) and VG3 neurons from the ventral cluster in embryonic brain slices. Dye injection and backfilling are used to document axogenesis and the progressive expansion of the dendritic arbor of the TCG from mid-embryogenesis up to hatching. Comparative maps of embryonic neuroblasts from several orthopteroid insects suggest equivalent deutocerebral neuroblasts from which the homologous TCG neurons already identified in the adult brain could originate. Our data offer the prospect of identifying further lineage-related neurons from the cluster and so understand a brain connectome from both a developmental and evolutionary perspective.}, } @article {pmid29666502, year = {2018}, author = {}, title = {Military work threatens science and security.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {273}, doi = {10.1038/d41586-018-04588-1}, pmid = {29666502}, issn = {1476-4687}, mesh = {Artificial Intelligence ; Military Science/economics/ethics/*methods ; *Research Personnel/economics/ethics/psychology ; Science/economics/ethics/*organization & administration ; Security Measures/*organization & administration ; Universities/economics/ethics/*organization & administration ; *Weapons/economics/ethics/legislation & jurisprudence ; Workforce ; }, } @article {pmid29666501, year = {2018}, author = {Peeples, L}, title = {Medicine's secret ingredient - it's in the timing.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {290-292}, doi = {10.1038/d41586-018-04600-8}, pmid = {29666501}, issn = {1476-4687}, mesh = {Aging/physiology ; Animals ; Antineoplastic Agents/administration & dosage/therapeutic use ; Circadian Rhythm/drug effects/*physiology ; *Drug Chronotherapy ; Drug Delivery Systems/*methods ; Female ; Glioblastoma/drug therapy ; Humans ; Male ; Mice ; Precision Medicine/*methods/trends ; Sex Characteristics ; Time Factors ; }, } @article {pmid29666500, year = {2018}, author = {Gewin, V}, title = {Space pioneer.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {399}, doi = {10.1038/d41586-018-04603-5}, pmid = {29666500}, issn = {1476-4687}, } @article {pmid29666498, year = {2018}, author = {Smith, AA}, title = {YouTube your science.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {397-398}, doi = {10.1038/d41586-018-04606-2}, pmid = {29666498}, issn = {1476-4687}, } @article {pmid29666497, year = {2018}, author = {}, title = {One NIH grant can lead to another.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {399}, doi = {10.1038/d41586-018-04605-3}, pmid = {29666497}, issn = {1476-4687}, } @article {pmid29666496, year = {2018}, author = {}, title = {Canadian universities fall short on diversity.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {399}, doi = {10.1038/d41586-018-04604-4}, pmid = {29666496}, issn = {1476-4687}, } @article {pmid29666490, year = {2018}, author = {Mashanovich, GZ}, title = {Electronics and photonics united.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {316-318}, doi = {10.1038/d41586-018-04443-3}, pmid = {29666490}, issn = {1476-4687}, mesh = {Electronics ; *Optics and Photonics ; *Physics ; }, } @article {pmid29666489, year = {2018}, author = {González-Rubio, G and Liz-Marzán, LM}, title = {Peptides used to make light-twisting nanoparticles.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {313-314}, doi = {10.1038/d41586-018-04205-1}, pmid = {29666489}, issn = {1476-4687}, mesh = {Light ; *Nanoparticles ; *Nanotechnology ; Optics and Photonics ; Peptides ; }, } @article {pmid29666488, year = {2018}, author = {Butler, D}, title = {Attacks in UK and Syria highlight growing need for chemical-forensics expertise.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {285-286}, doi = {10.1038/d41586-018-04533-2}, pmid = {29666488}, issn = {1476-4687}, mesh = {*Chemical Warfare/legislation & jurisprudence/prevention & control ; Female ; Forensic Toxicology/*standards ; Humans ; Male ; Nerve Agents/*analysis/*poisoning ; Russia ; Syria ; United Kingdom ; }, } @article {pmid29666487, year = {2018}, author = {Cyranoski, D}, title = {East Asia braces for surge in deadly tick-borne virus.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {282-283}, doi = {10.1038/d41586-018-04486-6}, pmid = {29666487}, issn = {1476-4687}, mesh = {Animals ; *Encephalitis, Tick-Borne ; Far East ; Humans ; Tick-Borne Diseases ; *Ticks ; }, } @article {pmid29666486, year = {2018}, author = {Catanzaro, M}, title = {Spain's biggest-ever science petition decries 'abandonment' of research.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {285}, doi = {10.1038/d41586-018-04523-4}, pmid = {29666486}, issn = {1476-4687}, mesh = {Budgets/*legislation & jurisprudence ; *Federal Government ; Research/*economics/*trends ; *Research Personnel/economics ; Research Support as Topic/economics/legislation & jurisprudence ; Spain ; }, } @article {pmid29666485, year = {2018}, author = {Tollefson, J}, title = {US environmental group wins millions to develop methane-monitoring satellite.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {283}, doi = {10.1038/d41586-018-04478-6}, pmid = {29666485}, issn = {1476-4687}, mesh = {Environmental Monitoring/*economics/*instrumentation ; Greenhouse Effect/economics/prevention & control/statistics & numerical data ; Methane/*analysis ; Oil and Gas Fields/chemistry ; Remote Sensing Technology/*economics/*instrumentation ; Satellite Communications/*economics ; United States ; }, } @article {pmid29666484, year = {2018}, author = {Wetsman, N}, title = {Air-pollution trackers seek to fill Africa's data gap.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {284}, doi = {10.1038/d41586-018-04330-x}, pmid = {29666484}, issn = {1476-4687}, mesh = {Africa ; *Air Pollution ; *Environmental Health ; }, } @article {pmid29666422, year = {2018}, author = {}, title = {Assessing chromatin accessibility.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {331}, doi = {10.1038/s41579-018-0018-z}, pmid = {29666422}, issn = {1740-1534}, } @article {pmid29666421, year = {2018}, author = {}, title = {A dormant state within cells.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {331}, doi = {10.1038/s41579-018-0016-1}, pmid = {29666421}, issn = {1740-1534}, } @article {pmid29666420, year = {2018}, author = {Wrighton, K}, title = {The STING behind dengue virus infection.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {330}, doi = {10.1038/s41579-018-0010-7}, pmid = {29666420}, issn = {1740-1534}, } @article {pmid29666319, year = {2018}, author = {Liu, H and Mi, Z and Lin, L and Wang, Y and Zhang, Z and Zhang, F and Wang, H and Liu, L and Zhu, B and Cao, G and Zhao, X and Sanders, NJ and Classen, AT and Reich, PB and He, JS}, title = {Shifting plant species composition in response to climate change stabilizes grassland primary production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4051-4056}, pmid = {29666319}, issn = {1091-6490}, mesh = {Biomass ; Carbon/metabolism ; *Carbon Sequestration ; China ; *Climate Change ; Conservation of Natural Resources/legislation & jurisprudence/statistics & numerical data ; Droughts ; *Ecosystem ; Environmental Monitoring ; *Grassland ; Human Activities ; Humans ; Humidity ; Longitudinal Studies ; Observational Studies as Topic ; *Plant Dispersal ; Plant Roots/growth & development/metabolism ; Poaceae/growth & development/metabolism ; Species Specificity ; Temperature ; Tibet ; *Tundra ; }, abstract = {The structure and function of alpine grassland ecosystems, including their extensive soil carbon stocks, are largely shaped by temperature. The Tibetan Plateau in particular has experienced significant warming over the past 50 y, and this warming trend is projected to intensify in the future. Such climate change will likely alter plant species composition and net primary production (NPP). Here we combined 32 y of observations and monitoring with a manipulative experiment of temperature and precipitation to explore the effects of changing climate on plant community structure and ecosystem function. First, long-term climate warming from 1983 to 2014, which occurred without systematic changes in precipitation, led to higher grass abundance and lower sedge abundance, but did not affect aboveground NPP. Second, an experimental warming experiment conducted over 4 y had no effects on any aspect of NPP, whereas drought manipulation (reducing precipitation by 50%), shifted NPP allocation belowground without affecting total NPP. Third, both experimental warming and drought treatments, supported by a meta-analysis at nine sites across the plateau, increased grass abundance at the expense of biomass of sedges and forbs. This shift in functional group composition led to deeper root systems, which may have enabled plant communities to acquire more water and thus stabilize ecosystem primary production even with a changing climate. Overall, our study demonstrates that shifting plant species composition in response to climate change may have stabilized primary production in this high-elevation ecosystem, but it also caused a shift from aboveground to belowground productivity.}, } @article {pmid29666318, year = {2018}, author = {Zhao, Y and Wang, M and Hu, S and Zhang, X and Ouyang, Z and Zhang, G and Huang, B and Zhao, S and Wu, J and Xie, D and Zhu, B and Yu, D and Pan, X and Xu, S and Shi, X}, title = {Economics- and policy-driven organic carbon input enhancement dominates soil organic carbon accumulation in Chinese croplands.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4045-4050}, pmid = {29666318}, issn = {1091-6490}, mesh = {Agriculture/economics/*methods ; Agrochemicals/chemistry ; Carbon/*analysis ; *Carbon Sequestration ; China ; Composting ; Conservation of Natural Resources/economics/*legislation & jurisprudence/statistics & numerical data ; Crops, Agricultural/chemistry ; Farms ; Human Activities ; Humans ; Organic Chemicals/*analysis ; Plant Dispersal ; Plant Roots/chemistry ; Plant Stems/chemistry ; Plants/chemistry ; *Policy ; Social Change ; Soil/*chemistry ; Soil Microbiology ; }, abstract = {China's croplands have experienced drastic changes in management practices, such as fertilization, tillage, and residue treatments, since the 1980s. There is an ongoing debate about the impact of these changes on soil organic carbon (SOC) and its implications. Here we report results from an extensive study that provided direct evidence of cropland SOC sequestration in China. Based on the soil sampling locations recorded by the Second National Soil Survey of China in 1980, we collected 4,060 soil samples in 2011 from 58 counties that represent the typical cropping systems across China. Our results showed that across the country, the average SOC stock in the topsoil (0-20 cm) increased from 28.6 Mg C ha-1 in 1980 to 32.9 Mg C ha-1 in 2011, representing a net increase of 140 kg C ha-1 year-1 However, the SOC change differed among the major agricultural regions: SOC increased in all major agronomic regions except in Northeast China. The SOC sequestration was largely attributed to increased organic inputs driven by economics and policy: while higher root biomass resulting from enhanced crop productivity by chemical fertilizers predominated before 2000, higher residue inputs following the large-scale implementation of crop straw/stover return policy took over thereafter. The SOC change was negatively related to N inputs in East China, suggesting that the excessive N inputs, plus the shallowness of plow layers, may constrain the future C sequestration in Chinese croplands. Our results indicate that cropland SOC sequestration can be achieved through effectively manipulating economic and policy incentives to farmers.}, } @article {pmid29666317, year = {2018}, author = {Lu, F and Hu, H and Sun, W and Zhu, J and Liu, G and Zhou, W and Zhang, Q and Shi, P and Liu, X and Wu, X and Zhang, L and Wei, X and Dai, L and Zhang, K and Sun, Y and Xue, S and Zhang, W and Xiong, D and Deng, L and Liu, B and Zhou, L and Zhang, C and Zheng, X and Cao, J and Huang, Y and He, N and Zhou, G and Bai, Y and Xie, Z and Tang, Z and Wu, B and Fang, J and Liu, G and Yu, G}, title = {Effects of national ecological restoration projects on carbon sequestration in China from 2001 to 2010.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4039-4044}, pmid = {29666317}, issn = {1091-6490}, mesh = {Biomass ; Carbon/*analysis ; *Carbon Sequestration ; China ; *Conservation of Natural Resources/legislation & jurisprudence/statistics & numerical data ; *Ecosystem ; Forests ; Grassland ; Humans ; Plants/chemistry ; Program Evaluation ; Soil/chemistry ; Water Movements ; }, abstract = {The long-term stressful utilization of forests and grasslands has led to ecosystem degradation and C loss. Since the late 1970s China has launched six key national ecological restoration projects to protect its environment and restore degraded ecosystems. Here, we conducted a large-scale field investigation and a literature survey of biomass and soil C in China's forest, shrubland, and grassland ecosystems across the regions where the six projects were implemented (∼16% of the country's land area). We investigated the changes in the C stocks of these ecosystems to evaluate the contributions of the projects to the country's C sink between 2001 and 2010. Over this decade, we estimated that the total annual C sink in the project region was 132 Tg C per y (1 Tg = 1012 g), over half of which (74 Tg C per y, 56%) was attributed to the implementation of the projects. Our results demonstrate that these restoration projects have substantially contributed to CO2 mitigation in China.}, } @article {pmid29666316, year = {2018}, author = {Tang, Z and Xu, W and Zhou, G and Bai, Y and Li, J and Tang, X and Chen, D and Liu, Q and Ma, W and Xiong, G and He, H and He, N and Guo, Y and Guo, Q and Zhu, J and Han, W and Hu, H and Fang, J and Xie, Z}, title = {Patterns of plant carbon, nitrogen, and phosphorus concentration in relation to productivity in China's terrestrial ecosystems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4033-4038}, pmid = {29666316}, issn = {1091-6490}, mesh = {Atmosphere/chemistry ; Biomass ; Carbon/*analysis ; *Carbon Sequestration ; China ; Climate ; *Ecosystem ; Farms ; Forests ; Grassland ; Humans ; Nitrogen/*analysis ; Organ Specificity ; Phosphorus/*analysis ; Plant Dispersal ; Plant Leaves/chemistry ; Plant Roots/chemistry ; Plant Stems/chemistry ; Plants/*chemistry ; Soil/chemistry ; Species Specificity ; }, abstract = {Plant nitrogen (N) and phosphorus (P) content regulate productivity and carbon (C) sequestration in terrestrial ecosystems. Estimates of the allocation of N and P content in plant tissues and the relationship between nutrient content and photosynthetic capacity are critical to predicting future ecosystem C sequestration under global change. In this study, by investigating the nutrient concentrations of plant leaves, stems, and roots across China's terrestrial biomes, we document large-scale patterns of community-level concentrations of C, N, and P. We also examine the possible correlation between nutrient content and plant production as indicated by vegetation gross primary productivity (GPP). The nationally averaged community concentrations of C, N, and P were 436.8, 14.14, and 1.11 mg·g-1 for leaves; 448.3, 3.04 and 0.31 mg·g-1 for stems; and 418.2, 4.85, and 0.47 mg·g-1 for roots, respectively. The nationally averaged leaf N and P productivity was 249.5 g C GPP·g-1 N·y-1 and 3,157.9 g C GPP·g-1 P·y-1, respectively. The N and P concentrations in stems and roots were generally more sensitive to the abiotic environment than those in leaves. There were strong power-law relationships between N (or P) content in different tissues for all biomes, which were closely coupled with vegetation GPP. These findings not only provide key parameters to develop empirical models to scale the responses of plants to global change from a single tissue to the whole community but also offer large-scale evidence of biome-dependent regulation of C sequestration by nutrients.}, } @article {pmid29666315, year = {2018}, author = {Chen, S and Wang, W and Xu, W and Wang, Y and Wan, H and Chen, D and Tang, Z and Tang, X and Zhou, G and Xie, Z and Zhou, D and Shangguan, Z and Huang, J and He, JS and Wang, Y and Sheng, J and Tang, L and Li, X and Dong, M and Wu, Y and Wang, Q and Wang, Z and Wu, J and Chapin, FS and Bai, Y}, title = {Plant diversity enhances productivity and soil carbon storage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4027-4032}, pmid = {29666315}, issn = {1091-6490}, mesh = {*Biodiversity ; Biomass ; Carbon/*analysis ; *Carbon Sequestration ; China ; Conservation of Natural Resources ; Datasets as Topic ; *Ecosystem ; Farms ; Forests ; Grassland ; Human Activities ; Humans ; Hydrogen-Ion Concentration ; Nitrogen/analysis ; Plant Dispersal ; Plants/chemistry/classification/*metabolism ; Rain ; Soil/*chemistry ; Temperature ; }, abstract = {Despite evidence from experimental grasslands that plant diversity increases biomass production and soil organic carbon (SOC) storage, it remains unclear whether this is true in natural ecosystems, especially under climatic variations and human disturbances. Based on field observations from 6,098 forest, shrubland, and grassland sites across China and predictions from an integrative model combining multiple theories, we systematically examined the direct effects of climate, soils, and human impacts on SOC storage versus the indirect effects mediated by species richness (SR), aboveground net primary productivity (ANPP), and belowground biomass (BB). We found that favorable climates (high temperature and precipitation) had a consistent negative effect on SOC storage in forests and shrublands, but not in grasslands. Climate favorability, particularly high precipitation, was associated with both higher SR and higher BB, which had consistent positive effects on SOC storage, thus offsetting the direct negative effect of favorable climate on SOC. The indirect effects of climate on SOC storage depended on the relationships of SR with ANPP and BB, which were consistently positive in all biome types. In addition, human disturbance and soil pH had both direct and indirect effects on SOC storage, with the indirect effects mediated by changes in SR, ANPP, and BB. High soil pH had a consistently negative effect on SOC storage. Our findings have important implications for improving global carbon cycling models and ecosystem management: Maintaining high levels of diversity can enhance soil carbon sequestration and help sustain the benefits of plant diversity and productivity.}, } @article {pmid29666314, year = {2018}, author = {Tang, X and Zhao, X and Bai, Y and Tang, Z and Wang, W and Zhao, Y and Wan, H and Xie, Z and Shi, X and Wu, B and Wang, G and Yan, J and Ma, K and Du, S and Li, S and Han, S and Ma, Y and Hu, H and He, N and Yang, Y and Han, W and He, H and Yu, G and Fang, J and Zhou, G}, title = {Carbon pools in China's terrestrial ecosystems: New estimates based on an intensive field survey.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4021-4026}, pmid = {29666314}, issn = {1091-6490}, mesh = {Biomass ; Carbon/*analysis ; *Carbon Sequestration ; China ; Conservation of Natural Resources/legislation & jurisprudence/statistics & numerical data ; *Ecosystem ; Farms ; Forests ; Grassland ; Human Activities ; Humans ; Plant Dispersal ; Plants/chemistry ; Rain ; Research Report ; Soil/chemistry ; Specimen Handling ; Surveys and Questionnaires ; Temperature ; }, abstract = {China's terrestrial ecosystems have functioned as important carbon sinks. However, previous estimates of carbon budgets have included large uncertainties owing to the limitations of sample size, multiple data sources, and inconsistent methodologies. In this study, we conducted an intensive field campaign involving 14,371 field plots to investigate all sectors of carbon stocks in China's forests, shrublands, grasslands, and croplands to better estimate the regional and national carbon pools and to explore the biogeographical patterns and potential drivers of these pools. The total carbon pool in these four ecosystems was 79.24 ± 2.42 Pg C, of which 82.9% was stored in soil (to a depth of 1 m), 16.5% in biomass, and 0.60% in litter. Forests, shrublands, grasslands, and croplands contained 30.83 ± 1.57 Pg C, 6.69 ± 0.32 Pg C, 25.40 ± 1.49 Pg C, and 16.32 ± 0.41 Pg C, respectively. When all terrestrial ecosystems are taken into account, the country's total carbon pool is 89.27 ± 1.05 Pg C. The carbon density of the forests, shrublands, and grasslands exhibited a strong correlation with climate: it decreased with increasing temperature but increased with increasing precipitation. Our analysis also suggests a significant sequestration potential of 1.9-3.4 Pg C in forest biomass in the next 10-20 years assuming no removals, mainly because of forest growth. Our results update the estimates of carbon pools in China's terrestrial ecosystems based on direct field measurements, and these estimates are essential to the validation and parameterization of carbon models in China and globally.}, } @article {pmid29666313, year = {2018}, author = {Fang, J and Yu, G and Liu, L and Hu, S and Chapin, FS}, title = {Climate change, human impacts, and carbon sequestration in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4015-4020}, pmid = {29666313}, issn = {1091-6490}, mesh = {Agriculture/economics/methods ; Agrochemicals/toxicity ; Carbon/analysis ; *Carbon Sequestration ; China ; *Climate Change/economics/statistics & numerical data ; Conservation of Natural Resources/economics/legislation & jurisprudence/statistics & numerical data ; Ecosystem ; Environmental Pollution/economics/legislation & jurisprudence/prevention & control/statistics & numerical data ; *Human Activities ; Humans ; Plant Dispersal ; }, } @article {pmid29666311, year = {2018}, author = {Arnold, C}, title = {News Feature: The quest to solve sepsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {3988-3991}, pmid = {29666311}, issn = {1091-6490}, mesh = {Animals ; Apoptosis ; Biomarkers ; Early Diagnosis ; Endotoxins/immunology ; Genome-Wide Association Study ; Host-Pathogen Interactions/genetics/immunology ; Humans ; Immune Tolerance/genetics ; Inflammation ; Lymphocytes/pathology ; Mice ; Multiple Organ Failure/etiology/prevention & control ; Sepsis/diagnosis/genetics/immunology/*physiopathology ; Superinfection/etiology/immunology ; Transcriptome ; }, } @article {pmid29666280, year = {2018}, author = {Ellis, L and Loda, M}, title = {LSD1: A single target to combat lineage plasticity in lethal prostate cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4530-4531}, pmid = {29666280}, issn = {1091-6490}, mesh = {Cell Line, Tumor ; *Histone Demethylases ; Humans ; Male ; *Prostatic Neoplasms ; }, } @article {pmid29666279, year = {2018}, author = {Riascos-Bernal, DF and Sibinga, NES and Kitsis, RN}, title = {PDCD5 says no to NO.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4535-4537}, pmid = {29666279}, issn = {1091-6490}, support = {R01 HL138475/HL/NHLBI NIH HHS/United States ; R01 HL128066/HL/NHLBI NIH HHS/United States ; R01 HL130861/HL/NHLBI NIH HHS/United States ; R01 HL128071/HL/NHLBI NIH HHS/United States ; R01 HL133861/HL/NHLBI NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; R01 CA170911/CA/NCI NIH HHS/United States ; R01 HL127700/HL/NHLBI NIH HHS/United States ; }, mesh = {Apoptosis ; *Apoptosis Regulatory Proteins ; *Neoplasm Proteins ; }, } @article {pmid29666278, year = {2018}, author = {Deng, T and Yan, G and Song, X and Xie, L and Zhou, Y and Li, J and Hu, X and Li, Z and Hu, J and Zhang, Y and Zhang, H and Sun, Y and Feng, P and Wei, D and Hu, B and Liu, J and Tan, W and Ye, M}, title = {Deubiquitylation and stabilization of p21 by USP11 is critical for cell-cycle progression and DNA damage responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4678-4683}, pmid = {29666278}, issn = {1091-6490}, support = {T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {A549 Cells ; Apoptosis/genetics ; *Cell Cycle ; Cell Nucleus/genetics/*metabolism ; Cyclin-Dependent Kinase Inhibitor p21/genetics/*metabolism ; *DNA Damage ; HEK293 Cells ; Humans ; Proteolysis ; *Signal Transduction ; Ubiquitin-Specific Proteases/genetics/*metabolism ; Ubiquitination/genetics ; }, abstract = {p21WAF1/CIP1 is a broad-acting cyclin-dependent kinase inhibitor. Its stability is essential for proper cell-cycle progression and cell fate decision. Ubiquitylation by the multiple E3 ubiquitin ligase complexes is the major regulatory mechanism of p21, which induces p21 degradation. However, it is unclear whether ubiquitylated p21 can be recycled. In this study, we report USP11 as a deubiquitylase of p21. In the nucleus, USP11 binds to p21, catalyzes the removal of polyubiquitin chains conjugated onto p21, and stabilizes p21 protein. As a result, USP11 reverses p21 polyubiquitylation and degradation mediated by SCFSKP2, CRL4CDT2, and APC/CCDC20 in a cell-cycle-independent manner. Loss of USP11 causes the destabilization of p21 and induces the G1/S transition in unperturbed cells. Furthermore, p21 accumulation mediated by DNA damage is completely abolished in cells depleted of USP11, which results in abrogation of the G2 checkpoint and induction of apoptosis. Functionally, USP11-mediated stabilization of p21 inhibits cell proliferation and tumorigenesis in vivo. These findings reveal an important mechanism by which p21 can be stabilized by direct deubiquitylation, and they pinpoint a crucial role of the USP11-p21 axis in regulating cell-cycle progression and DNA damage responses.}, } @article {pmid29666277, year = {2018}, author = {Robertson, NO and Smith, NC and Manakas, A and Mahjoub, M and McDonald, G and Kwan, AH and Matthews, JM}, title = {Disparate binding kinetics by an intrinsically disordered domain enables temporal regulation of transcriptional complex formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4643-4648}, pmid = {29666277}, issn = {1091-6490}, mesh = {Animals ; DNA/*chemistry/genetics/metabolism ; DNA-Binding Proteins/*chemistry/genetics/metabolism ; Intrinsically Disordered Proteins/*chemistry/genetics/metabolism ; Kinetics ; LIM Domain Proteins/*chemistry/genetics/metabolism ; LIM-Homeodomain Proteins/*chemistry/genetics/metabolism ; Mice ; Multiprotein Complexes/*chemistry/genetics/metabolism ; Protein Binding ; Protein Domains ; Transcription Factors/*chemistry/genetics/metabolism ; *Transcription Initiation, Genetic ; }, abstract = {Intrinsically disordered regions are highly represented among mammalian transcription factors, where they often contribute to the formation of multiprotein complexes that regulate gene expression. An example of this occurs with LIM-homeodomain (LIM-HD) proteins in the developing spinal cord. The LIM-HD protein LHX3 and the LIM-HD cofactor LDB1 form a binary complex that gives rise to interneurons, whereas in adjacent cell populations, LHX3 and LDB1 form a rearranged ternary complex with the LIM-HD protein ISL1, resulting in motor neurons. The protein-protein interactions within these complexes are mediated by ordered LIM domains in the LIM-HD proteins and intrinsically disordered LIM interaction domains (LIDs) in LDB1 and ISL1; however, little is known about how the strength or rates of binding contribute to complex assemblies. We have measured the interactions of LIM:LID complexes using FRET-based protein-protein interaction studies and EMSAs and used these data to model population distributions of complexes. The protein-protein interactions within the ternary complexes are much weaker than those in the binary complex, yet surprisingly slow LDB1:ISL1 dissociation kinetics and a substantial increase in DNA binding affinity promote formation of the ternary complex over the binary complex in motor neurons. We have used mutational and protein engineering approaches to show that allostery and modular binding by tandem LIM domains contribute to the LDB1LID binding kinetics. The data indicate that a single intrinsically disordered region can achieve highly disparate binding kinetics, which may provide a mechanism to regulate the timing of transcriptional complex assembly.}, } @article {pmid29666276, year = {2018}, author = {Denk, J and Kretschmer, S and Halatek, J and Hartl, C and Schwille, P and Frey, E}, title = {MinE conformational switching confers robustness on self-organized Min protein patterns.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4553-4558}, pmid = {29666276}, issn = {1091-6490}, mesh = {Adenosine Triphosphatases/metabolism/physiology ; Adenosine Triphosphate/metabolism ; Cell Cycle Proteins/*metabolism/*physiology ; Cell Division ; Cell Membrane/metabolism ; Cytoplasm/metabolism ; Escherichia coli/genetics/metabolism ; Escherichia coli Proteins/genetics/*metabolism/*physiology ; Membrane Proteins/metabolism ; Models, Theoretical ; Molecular Conformation ; Protein Binding/physiology ; }, abstract = {Protein patterning is vital for many fundamental cellular processes. This raises two intriguing questions: Can such intrinsically complex processes be reduced to certain core principles and, if so, what roles do the molecular details play in individual systems? A prototypical example for protein patterning is the bacterial Min system, in which self-organized pole-to-pole oscillations of MinCDE proteins guide the cell division machinery to midcell. These oscillations are based on cycling of the ATPase MinD and its activating protein MinE between the membrane and the cytoplasm. Recent biochemical evidence suggests that MinE undergoes a reversible, MinD-dependent conformational switch from a latent to a reactive state. However, the functional relevance of this switch for the Min network and pattern formation remains unclear. By combining mathematical modeling and in vitro reconstitution of mutant proteins, we dissect the two aspects of MinE's switch, persistent membrane binding and a change in MinE's affinity for MinD. Our study shows that the MinD-dependent change in MinE's binding affinity for MinD is essential for patterns to emerge over a broad and physiological range of protein concentrations. Mechanistically, our results suggest that conformational switching of an ATPase-activating protein can lead to the spatial separation of its distinct functional states and thereby confer robustness on an intracellular protein network with vital roles in bacterial cell division.}, } @article {pmid29666275, year = {2018}, author = {Lancaster, KM}, title = {Sizing up a supercharged ferryl.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4532-4534}, pmid = {29666275}, issn = {1091-6490}, mesh = {*Hydrogen Peroxide ; *Iron ; }, } @article {pmid29666274, year = {2018}, author = {Okabayashi, N and Peronio, A and Paulsson, M and Arai, T and Giessibl, FJ}, title = {Vibrations of a molecule in an external force field.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4571-4576}, pmid = {29666274}, issn = {1091-6490}, abstract = {The oscillation frequencies of a molecule on a surface are determined by the mass distribution in the molecule and the restoring forces that occur when the molecule bends. The restoring force originates from the atomic-scale interaction within the molecule and with the surface, which plays an essential role in the dynamics and reactivity of the molecule. In 1998, a combination of scanning tunneling microscopy with inelastic tunneling spectroscopy revealed the vibrational frequencies of single molecules adsorbed on a surface. However, the probe tip itself exerts forces on the molecule, changing its oscillation frequencies. Here, we combine atomic force microscopy with inelastic tunneling spectroscopy and measure the influence of the forces exerted by the tip on the lateral vibrational modes of a carbon monoxide molecule on a copper surface. Comparing the experimental data to a mechanical model of the vibrating molecule shows that the bonds within the molecule and with the surface are weakened by the proximity of the tip. This combination of techniques can be applied to analyze complex molecular vibrations and the mechanics of forming and loosening chemical bonds, as well as to study the mechanics of bond breaking in chemical reactions and atomic manipulation.}, } @article {pmid29666273, year = {2018}, author = {Robinson, A and Busula, AO and Voets, MA and Beshir, KB and Caulfield, JC and Powers, SJ and Verhulst, NO and Winskill, P and Muwanguzi, J and Birkett, MA and Smallegange, RC and Masiga, DK and Mukabana, WR and Sauerwein, RW and Sutherland, CJ and Bousema, T and Pickett, JA and Takken, W and Logan, JG and de Boer, JG}, title = {Plasmodium-associated changes in human odor attract mosquitoes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4209-E4218}, pmid = {29666273}, issn = {1091-6490}, support = {//Medical Research Council/United Kingdom ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Anopheles/*physiology ; Child ; Child, Preschool ; Female ; Humans ; *Malaria/metabolism/transmission ; Male ; Mosquito Vectors/*physiology ; *Odorants ; Plasmodium/*metabolism ; }, abstract = {Malaria parasites (Plasmodium) can change the attractiveness of their vertebrate hosts to Anopheles vectors, leading to a greater number of vector-host contacts and increased transmission. Indeed, naturally Plasmodium-infected children have been shown to attract more mosquitoes than parasite-free children. Here, we demonstrate Plasmodium-induced increases in the attractiveness of skin odor in Kenyan children and reveal quantitative differences in the production of specific odor components in infected vs. parasite-free individuals. We found the aldehydes heptanal, octanal, and nonanal to be produced in greater amounts by infected individuals and detected by mosquito antennae. In behavioral experiments, we demonstrated that these, and other, Plasmodium-induced aldehydes enhanced the attractiveness of a synthetic odor blend mimicking "healthy" human odor. Heptanal alone increased the attractiveness of "parasite-free" natural human odor. Should the increased production of these aldehydes by Plasmodium-infected humans lead to increased mosquito biting in a natural setting, this would likely affect the transmission of malaria.}, } @article {pmid29666272, year = {2018}, author = {Kadirvelraj, R and Yang, JY and Sanders, JH and Liu, L and Ramiah, A and Prabhakar, PK and Boons, GJ and Wood, ZA and Moremen, KW}, title = {Human N-acetylglucosaminyltransferase II substrate recognition uses a modular architecture that includes a convergent exosite.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4637-4642}, pmid = {29666272}, issn = {1091-6490}, support = {P01 GM107012/GM/NIGMS NIH HHS/United States ; P41 GM103390/GM/NIGMS NIH HHS/United States ; R01 GM114298/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; N-Acetylglucosaminyltransferases/*chemistry/metabolism ; Protein Domains ; *Protein Folding ; Uridine Diphosphate N-Acetylglucosamine/*chemistry/metabolism ; }, abstract = {Asn-linked oligosaccharides are extensively modified during transit through the secretory pathway, first by trimming of the nascent glycan chains and subsequently by initiating and extending multiple oligosaccharide branches from the trimannosyl glycan core. Trimming and branching pathway steps are highly ordered and hierarchal based on the precise substrate specificities of the individual biosynthetic enzymes. A key committed step in the synthesis of complex-type glycans is catalyzed by N-acetylglucosaminyltransferase II (MGAT2), an enzyme that generates the second GlcNAcβ1,2- branch from the trimannosyl glycan core using UDP-GlcNAc as the sugar donor. We determined the structure of human MGAT2 as a Mn2+-UDP donor analog complex and as a GlcNAcMan3GlcNAc2-Asn acceptor complex to reveal the structural basis for substrate recognition and catalysis. The enzyme exhibits a GT-A Rossmann-like fold that employs conserved divalent cation-dependent substrate interactions with the UDP-GlcNAc donor. MGAT2 interactions with the extended glycan acceptor are distinct from other related glycosyltransferases. These interactions are composed of a catalytic subsite that binds the Man-α1,6- monosaccharide acceptor and a distal exosite pocket that binds the GlcNAc-β1,2Man-α1,3Manβ- substrate "recognition arm." Recognition arm interactions are similar to the enzyme-substrate interactions for Golgi α-mannosidase II, a glycoside hydrolase that acts just before MGAT2 in the Asn-linked glycan biosynthetic pathway. These data suggest that substrate binding by MGAT2 employs both conserved and convergent catalytic subsite modules to provide substrate selectivity and catalysis. More broadly, the MGAT2 active-site architecture demonstrates how glycosyltransferases create complementary modular templates for regiospecific extension of glycan structures in mammalian cells.}, } @article {pmid29666271, year = {2018}, author = {Mizrahi-Kliger, AD and Kaplan, A and Israel, Z and Bergman, H}, title = {Desynchronization of slow oscillations in the basal ganglia during natural sleep.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4274-E4283}, pmid = {29666271}, issn = {1091-6490}, mesh = {Animals ; Basal Ganglia/*physiology ; Biological Clocks/*physiology ; Brain Waves/*physiology ; Cercopithecus aethiops ; Female ; Membrane Potentials/*physiology ; Nerve Net/*physiology ; Sleep/*physiology ; }, abstract = {Slow oscillations of neuronal activity alternating between firing and silence are a hallmark of slow-wave sleep (SWS). These oscillations reflect the default activity present in all mammalian species, and are ubiquitous to anesthesia, brain slice preparations, and neuronal cultures. In all these cases, neuronal firing is highly synchronous within local circuits, suggesting that oscillation-synchronization coupling may be a governing principle of sleep physiology regardless of anatomical connectivity. To investigate whether this principle applies to overall brain organization, we recorded the activity of individual neurons from basal ganglia (BG) structures and the thalamocortical (TC) network over 70 full nights of natural sleep in two vervet monkeys. During SWS, BG neurons manifested slow oscillations (∼0.5 Hz) in firing rate that were as prominent as in the TC network. However, in sharp contrast to any neural substrate explored thus far, the slow oscillations in all BG structures were completely desynchronized between individual neurons. Furthermore, whereas in the TC network single-cell spiking was locked to slow oscillations in the local field potential (LFP), the BG LFP exhibited only weak slow oscillatory activity and failed to entrain nearby cells. We thus show that synchrony is not inherent to slow oscillations, and propose that the BG desynchronization of slow oscillations could stem from its unique anatomy and functional connectivity. Finally, we posit that BG slow-oscillation desynchronization may further the reemergence of slow-oscillation traveling waves from multiple independent origins in the frontal cortex, thus significantly contributing to normal SWS.}, } @article {pmid29666270, year = {2018}, author = {Suarez-Lopez, L and Sriram, G and Kong, YW and Morandell, S and Merrick, KA and Hernandez, Y and Haigis, KM and Yaffe, MB}, title = {MK2 contributes to tumor progression by promoting M2 macrophage polarization and tumor angiogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4236-E4244}, pmid = {29666270}, issn = {1091-6490}, support = {P30 CA014051/CA/NCI NIH HHS/United States ; R01 ES015339/ES/NIEHS NIH HHS/United States ; R01 GM104047/GM/NIGMS NIH HHS/United States ; R35 ES028374/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Colorectal Neoplasms/*blood supply/*epidemiology/genetics/pathology ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Macrophages/*enzymology/pathology ; Mice ; Mice, Knockout ; Neoplasm Proteins/genetics/*metabolism ; Neovascularization, Pathologic/*enzymology/genetics/pathology ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; }, abstract = {Chronic inflammation is a major risk factor for colorectal cancer. The p38/MAPKAP Kinase 2 (MK2) kinase axis controls the synthesis of proinflammatory cytokines that mediate both chronic inflammation and tumor progression. Blockade of this pathway has been previously reported to suppress inflammation and to prevent colorectal tumorigenesis in a mouse model of inflammation-driven colorectal cancer, by mechanisms that are still unclear. Here, using whole-animal and tissue-specific MK2 KO mice, we show that MK2 activity in the myeloid compartment promotes tumor progression by supporting tumor neoangiogenesis in vivo. Mechanistically, we demonstrate that MK2 promotes polarization of tumor-associated macrophages into protumorigenic, proangiogenic M2-like macrophages. We further confirmed our results in human cell lines, where MK2 chemical inhibition in macrophages impairs M2 polarization and M2 macrophage-induced angiogenesis. Together, this study provides a molecular and cellular mechanism for the protumorigenic function of MK2.}, } @article {pmid29666269, year = {2018}, author = {DeMille, MMC and Tang, K and Mehta, CM and Geissler, C and Malins, JG and Powers, NR and Bowen, BM and Adams, AK and Truong, DT and Frijters, JC and Gruen, JR}, title = {Worldwide distribution of the DCDC2 READ1 regulatory element and its relationship with phoneme variation across languages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4951-4956}, pmid = {29666269}, issn = {1091-6490}, support = {P50 HD027802/HD/NICHD NIH HHS/United States ; R01 NS043530/NS/NINDS NIH HHS/United States ; T32 HD007094/HD/NICHD NIH HHS/United States ; T32 HD007149/HD/NICHD NIH HHS/United States ; }, mesh = {*Alleles ; Animals ; *Genetic Variation ; Hominidae ; Humans ; *Language ; Microtubule-Associated Proteins/*genetics ; *Response Elements ; }, abstract = {DCDC2 is a gene strongly associated with components of the phonological processing system in animal models and in multiple independent studies of populations and languages. We propose that it may also influence population-level variation in language component usage. To test this hypothesis, we investigated the evolution and worldwide distribution of the READ1 regulatory element within DCDC2, and compared its distribution with variation in different language properties. The mutational history of READ1 was estimated by examining primate and archaic hominin sequences. This identified duplication and expansion events, which created a large number of polymorphic alleles based on internal repeat units (RU1 and RU2). Association of READ1 alleles was studied with respect to the numbers of consonants and vowels for languages in 43 human populations distributed across five continents. Using population-based approaches with multivariate ANCOVA and linear mixed effects analyses, we found that the RU1-1 allele group of READ1 is significantly associated with the number of consonants within languages independent of genetic relatedness, geographic proximity, and language family. We propose that allelic variation in READ1 helped create a subtle cognitive bias that was amplified by cultural transmission, and ultimately shaped consonant use by different populations over time.}, } @article {pmid29666268, year = {2018}, author = {}, title = {Correction for DuBose et al., Everolimus rescues multiple cellular defects in laminopathy-patient fibroblasts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4140}, doi = {10.1073/pnas.1805694115}, pmid = {29666268}, issn = {1091-6490}, } @article {pmid29666267, year = {2018}, author = {}, title = {Correction for Kristensen et al., Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4143}, doi = {10.1073/pnas.1805313115}, pmid = {29666267}, issn = {1091-6490}, } @article {pmid29666266, year = {2018}, author = {Li, Y and Hamilton, KJ and Wang, T and Coons, LA and Jefferson, WN and Li, R and Wang, Y and Grimm, SA and Ramsey, JT and Liu, L and Gerrish, KE and Williams, CJ and Wade, PA and Korach, KS}, title = {DNA methylation and transcriptome aberrations mediated by ERα in mouse seminal vesicles following developmental DES exposure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4189-E4198}, pmid = {29666266}, issn = {1091-6490}, support = {ZIA ES070065/ES/NIEHS NIH HHS/United States ; ZIA ES102985/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; DNA Methylation/*drug effects/genetics ; Diethylstilbestrol/*adverse effects/pharmacology ; Estrogen Receptor alpha/agonists/genetics/*metabolism ; Estrogens, Non-Steroidal/*adverse effects/pharmacology ; Gene Expression Regulation/*drug effects ; Genetic Loci ; Male ; Mice ; Mice, Knockout ; Seminal Vesicles/*metabolism ; Transcriptome/*drug effects ; }, abstract = {Early transient developmental exposure to an endocrine active compound, diethylstilbestrol (DES), a synthetic estrogen, causes late-stage effects in the reproductive tract of adult mice. Estrogen receptor alpha (ERα) plays a role in mediating these developmental effects. However, the developmental mechanism is not well known in male tissues. Here, we present genome-wide transcriptome and DNA methylation profiling of the seminal vesicles (SVs) during normal development and after DES exposure. ERα mediates aberrations of the mRNA transcriptome in SVs of adult mice following neonatal DES exposure. This developmental exposure impacts differential diseases between male (SVs) and female (uterus) tissues when mice reach adulthood due to most DES-altered genes that appear to be tissue specific during mouse development. Certain estrogen-responsive gene changes in SVs are cell-type specific. DNA methylation dynamically changes during development in the SVs of wild-type (WT) and ERα-knockout (αERKO) mice, which increases both the loss and gain of differentially methylated regions (DMRs). There are more gains of DMRs in αERKO compared with WT. Interestingly, the methylation changes between the two genotypes are in different genomic loci. Additionally, the expression levels of a subset of DES-altered genes are associated with their DNA methylation status following developmental DES exposure. Taken together, these findings provide an important basis for understanding the molecular and cellular mechanism of endocrine-disrupting chemicals (EDCs), such as DES, during development in the male mouse tissues. This unique evidence contributes to our understanding of developmental actions of EDCs in human health.}, } @article {pmid29666265, year = {2018}, author = {Ghosal, S and Blystone, D and Singh, AK and Ganapathysubramanian, B and Singh, A and Sarkar, S}, title = {An explainable deep machine vision framework for plant stress phenotyping.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4613-4618}, pmid = {29666265}, issn = {1091-6490}, mesh = {Machine Learning ; Phenotype ; Plant Breeding/methods ; Plant Diseases/*classification ; Plant Leaves/classification/metabolism ; Plant Physiological Phenomena ; Plants ; Soybeans/*metabolism ; Stress, Physiological/*physiology ; }, abstract = {Current approaches for accurate identification, classification, and quantification of biotic and abiotic stresses in crop research and production are predominantly visual and require specialized training. However, such techniques are hindered by subjectivity resulting from inter- and intrarater cognitive variability. This translates to erroneous decisions and a significant waste of resources. Here, we demonstrate a machine learning framework's ability to identify and classify a diverse set of foliar stresses in soybean [Glycine max (L.) Merr.] with remarkable accuracy. We also present an explanation mechanism, using the top-K high-resolution feature maps that isolate the visual symptoms used to make predictions. This unsupervised identification of visual symptoms provides a quantitative measure of stress severity, allowing for identification (type of foliar stress), classification (low, medium, or high stress), and quantification (stress severity) in a single framework without detailed symptom annotation by experts. We reliably identified and classified several biotic (bacterial and fungal diseases) and abiotic (chemical injury and nutrient deficiency) stresses by learning from over 25,000 images. The learned model is robust to input image perturbations, demonstrating viability for high-throughput deployment. We also noticed that the learned model appears to be agnostic to species, seemingly demonstrating an ability of transfer learning. The availability of an explainable model that can consistently, rapidly, and accurately identify and quantify foliar stresses would have significant implications in scientific research, plant breeding, and crop production. The trained model could be deployed in mobile platforms (e.g., unmanned air vehicles and automated ground scouts) for rapid, large-scale scouting or as a mobile application for real-time detection of stress by farmers and researchers.}, } @article {pmid29666264, year = {2018}, author = {}, title = {Correction for Serr et al., miRNA92a targets KLF2 and the phosphatase PTEN signaling to promote human T follicular helper precursors in T1D islet autoimmunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4142}, doi = {10.1073/pnas.1805675115}, pmid = {29666264}, issn = {1091-6490}, } @article {pmid29666263, year = {2018}, author = {Samoray, C}, title = {Profile of Warren J. Leonard.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4305-4307}, pmid = {29666263}, issn = {1091-6490}, mesh = {Allergy and Immunology/*history ; Animals ; Cytokines/*genetics/*immunology ; History, 20th Century ; History, 21st Century ; Humans ; Portraits as Topic ; X-Linked Combined Immunodeficiency Diseases/*genetics/*history/*immunology/pathology ; }, } @article {pmid29666262, year = {2018}, author = {Daitch, AL and Parvizi, J}, title = {Spatial and temporal heterogeneity of neural responses in human posteromedial cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4785-4790}, pmid = {29666262}, issn = {1091-6490}, support = {F32 HD087028/HD/NICHD NIH HHS/United States ; R01 MH109954/MH/NIMH NIH HHS/United States ; R01 NS078396/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; Attention/*physiology ; Brain/*physiology ; *Electroencephalography ; Female ; Humans ; Male ; Memory/*physiology ; Middle Aged ; Thinking/*physiology ; }, abstract = {Neuroimaging evidence supports a role of the default mode network (DMN) in spontaneous thought and goal-driven internally oriented processes, such as recalling an autobiographical event, and has demonstrated its deactivation during focused, externally oriented attention. Recent work suggests that the DMN is not a homogeneous network but rather is composed of at least several subnetworks, which are engaged in distinct functions; however, it is still unclear if these different functions rely on the same neuronal populations. In this study, we used intracranial EEG to record from the posteromedial cortex (PMC), a core hub of the DMN, in 13 human subjects, during autobiographical memory retrieval (internally oriented), arithmetic processing (externally oriented), and cued rest (spontaneous thought), allowing us to measure activity from anatomically precise PMC sites with high temporal resolution. We observed a heterogeneous, yet spatially organized, pattern of activity across tasks. Many sites, primarily in the more ventral portion of PMC, were engaged during autobiographical recall and suppressed during arithmetic processing. Other more dorsal PMC sites were engaged during the cued-rest condition. Of these rest-active sites, some exhibited variable temporal dynamics across trials, possibly reflecting various forms of spontaneous thought, while others showed only transient activity at the beginning of cued-rest trials (i.e., after a switch from a task to cued rest), possibly involved in shifting the brain from a more focused to a more exploratory attentional state. These results suggest heterogeneity of function even within an individual node of the DMN.}, } @article {pmid29666261, year = {2018}, author = {Kumar, GS and Clarkson, MW and Kunze, MBA and Granata, D and Wand, AJ and Lindorff-Larsen, K and Page, R and Peti, W}, title = {Dynamic activation and regulation of the mitogen-activated protein kinase p38.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4655-4660}, pmid = {29666261}, issn = {1091-6490}, support = {R01 GM100910/GM/NIGMS NIH HHS/United States ; }, mesh = {Allosteric Regulation/physiology ; Enzyme Activation/physiology ; Humans ; *Molecular Dynamics Simulation ; Nuclear Magnetic Resonance, Biomolecular ; Phosphorylation/physiology ; Protein Structure, Secondary ; p38 Mitogen-Activated Protein Kinases/*chemistry/metabolism ; }, abstract = {Mitogen-activated protein kinases, which include p38, are essential for cell differentiation and autophagy. The current model for p38 activation involves activation-loop phosphorylation with subsequent substrate binding leading to substrate phosphorylation. Despite extensive efforts, the molecular mechanism of activation remains unclear. Here, using NMR spectroscopy, we show how the modulation of protein dynamics across timescales activates p38. We find that activation-loop phosphorylation does not change the average conformation of p38; rather it quenches the loop ps-ns dynamics. We then show that substrate binding to nonphosphorylated and phosphorylated p38 results in uniform µs-ms backbone dynamics at catalytically essential regions and across the entire molecule, respectively. Together, these results show that phosphorylation and substrate binding flatten the energy landscape of the protein, making essential elements of allostery and activation dynamically accessible. The high degree of structural conservation among ser/thr kinases suggests that elements of this mechanism may be conserved across the kinase family.}, } @article {pmid29666260, year = {2018}, author = {Ahmed, F}, title = {QnAs with Donald Geman.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4528-4529}, pmid = {29666260}, issn = {1091-6490}, mesh = {Algorithms ; Computational Biology/*methods ; Data Interpretation, Statistical ; Genomics/*methods ; Humans ; Precision Medicine/methods ; }, } @article {pmid29666259, year = {2018}, author = {Fu, J and Nogueira, SV and Drongelen, VV and Coit, P and Ling, S and Rosloniec, EF and Sawalha, AH and Holoshitz, J}, title = {Shared epitope-aryl hydrocarbon receptor crosstalk underlies the mechanism of gene-environment interaction in autoimmune arthritis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4755-4760}, pmid = {29666259}, issn = {1091-6490}, support = {T32 AR007080/AR/NIAMS NIH HHS/United States ; R21 ES024428/ES/NIEHS NIH HHS/United States ; R61 AR073014/AR/NIAMS NIH HHS/United States ; R01 GM088560/GM/NIGMS NIH HHS/United States ; P30 ES017885/ES/NIEHS NIH HHS/United States ; R01 AR059085/AR/NIAMS NIH HHS/United States ; }, mesh = {Alleles ; Animals ; *Arthritis, Experimental/genetics/immunology/pathology ; Environmental Pollutants/*immunology/toxicity ; Epitopes/*immunology ; *Gene-Environment Interaction ; Humans ; Mice ; Mice, Transgenic ; *Receptors, Aryl Hydrocarbon/genetics/immunology ; *Signal Transduction/genetics/immunology ; *Th17 Cells/immunology/pathology ; }, abstract = {The susceptibility to autoimmune diseases is affected by genetic and environmental factors. In rheumatoid arthritis (RA), the shared epitope (SE), a five-amino acid sequence motif encoded by RA-associated HLA-DRB1 alleles, is the single most significant genetic risk factor. The risk conferred by the SE is increased in a multiplicative way by exposure to various environmental pollutants, such as cigarette smoke. The mechanism of this synergistic interaction is unknown. It is worth noting that the SE has recently been found to act as a signal transduction ligand that facilitates differentiation of Th17 cells and osteoclasts in vitro and in vivo. Intriguingly, the aryl hydrocarbon receptor (AhR), a transcription factor that mediates the xenobiotic effects of many pollutants, including tobacco combustion products, has been found to activate similar biologic effects. Prompted by these similarities, we sought to determine whether the SE and AhR signaling pathways interact in autoimmune arthritis. Here we uncovered a nuclear factor kappa B-mediated synergistic interaction between the SE and AhR pathways that leads to markedly enhanced osteoclast differentiation and Th17 polarization in vitro. Administration of AhR pathway agonists to transgenic mice carrying human SE-coding alleles resulted in a robust increase in arthritis severity, bone destruction, overabundance of osteoclasts, and IL17-expressing cells in the inflamed joints and draining lymph nodes of arthritic mice. Thus, this study identifies a previously unrecognized mechanism of gene-environment interaction that could provide insights into the well-described but poorly understood amplification of the genetic risk for RA upon exposure to environmental pollutants.}, } @article {pmid29666258, year = {2018}, author = {Kim, J and Lei, Y and Guo, J and Kim, SE and Wlodarczyk, BJ and Cabrera, RM and Lin, YL and Nilsson, TK and Zhang, T and Ren, A and Wang, L and Yuan, Z and Zheng, YF and Wang, HY and Finnell, RH}, title = {Formate rescues neural tube defects caused by mutations in Slc25a32.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4690-4695}, pmid = {29666258}, issn = {1091-6490}, support = {P01 HD067244/HD/NICHD NIH HHS/United States ; R01 HD081216/HD/NICHD NIH HHS/United States ; R01 HD083809/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biological Transport, Active/genetics ; Formates/*pharmacology ; Humans ; Membrane Transport Proteins/*genetics/*metabolism ; Mice ; Mice, Transgenic ; *Mutation ; *Neural Tube/embryology/pathology ; *Neural Tube Defects/embryology/genetics/pathology/prevention & control ; }, abstract = {Periconceptional folic acid (FA) supplementation significantly reduces the prevalence of neural tube defects (NTDs). Unfortunately, some NTDs are FA resistant, and as such, NTDs remain a global public health concern. Previous studies have identified SLC25A32 as a mitochondrial folate transporter (MFT), which is capable of transferring tetrahydrofolate (THF) from cellular cytoplasm to the mitochondria in vitro. Herein, we show that gene trap inactivation of Slc25a32 (Mft) in mice induces NTDs that are folate (5-methyltetrahydrofolate, 5-mTHF) resistant yet are preventable by formate supplementation. Slc25a32gt/gt embryos die in utero with 100% penetrant cranial NTDs. 5-mTHF supplementation failed to promote normal neural tube closure (NTC) in mutant embryos, while formate supplementation enabled the majority (78%) of knockout embryos to complete NTC. A parallel genetic study in human subjects with NTDs identified biallelic loss of function SLC25A32 variants in a cranial NTD case. These data demonstrate that the loss of functional Slc25a32 results in cranial NTDs in mice and has also been observed in a human NTD patient.}, } @article {pmid29666257, year = {2018}, author = {Xu, X and Fukuda, K and Karki, A and Park, S and Kimura, H and Jinno, H and Watanabe, N and Yamamoto, S and Shimomura, S and Kitazawa, D and Yokota, T and Umezu, S and Nguyen, TQ and Someya, T}, title = {Thermally stable, highly efficient, ultraflexible organic photovoltaics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4589-4594}, pmid = {29666257}, issn = {1091-6490}, abstract = {Flexible photovoltaics with extreme mechanical compliance present appealing possibilities to power Internet of Things (IoT) sensors and wearable electronic devices. Although improvement in thermal stability is essential, simultaneous achievement of high power conversion efficiency (PCE) and thermal stability in flexible organic photovoltaics (OPVs) remains challenging due to the difficulties in maintaining an optimal microstructure of the active layer under thermal stress. The insufficient thermal capability of a plastic substrate and the environmental influences cannot be fully expelled by ultrathin barrier coatings. Here, we have successfully fabricated ultraflexible OPVs with initial efficiencies of up to 10% that can endure temperatures of over 100 °C, maintaining 80% of the initial efficiency under accelerated testing conditions for over 500 hours in air. Particularly, we introduce a low-bandgap poly(benzodithiophene-cothieno[3,4-b]thiophene) (PBDTTT) donor polymer that forms a sturdy microstructure when blended with a fullerene acceptor. We demonstrate a feasible way to adhere ultraflexible OPVs onto textiles through a hot-melt process without causing severe performance degradation.}, } @article {pmid29666256, year = {2018}, author = {Morris, PJ and Swindles, GT and Valdes, PJ and Ivanovic, RF and Gregoire, LJ and Smith, MW and Tarasov, L and Haywood, AM and Bacon, KL}, title = {Global peatland initiation driven by regionally asynchronous warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4851-4856}, pmid = {29666256}, issn = {1091-6490}, mesh = {Carbon/*metabolism ; *Global Warming ; *Models, Biological ; *Soil ; *Wetlands ; }, abstract = {Widespread establishment of peatlands since the Last Glacial Maximum represents the activation of a globally important carbon sink, but the drivers of peat initiation are unclear. The role of climate in peat initiation is particularly poorly understood. We used a general circulation model to simulate local changes in climate during the initiation of 1,097 peatlands around the world. We find that peat initiation in deglaciated landscapes in both hemispheres was driven primarily by warming growing seasons, likely through enhanced plant productivity, rather than by any increase in effective precipitation. In Western Siberia, which remained ice-free throughout the last glacial period, the initiation of the world's largest peatland complex was globally unique in that it was triggered by an increase in effective precipitation that inhibited soil respiration and allowed wetland plant communities to establish. Peat initiation in the tropics was only weakly related to climate change, and appears to have been driven primarily by nonclimatic mechanisms such as waterlogging due to tectonic subsidence. Our findings shed light on the genesis and Holocene climate space of one of the world's most carbon-dense ecosystem types, with implications for understanding trajectories of ecological change under changing future climates.}, } @article {pmid29666255, year = {2018}, author = {Dinalankara, W and Ke, Q and Xu, Y and Ji, L and Pagane, N and Lien, A and Matam, T and Fertig, EJ and Price, ND and Younes, L and Marchionni, L and Geman, D}, title = {Digitizing omics profiles by divergence from a baseline.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4545-4552}, pmid = {29666255}, issn = {1091-6490}, support = {R01 CA177669/CA/NCI NIH HHS/United States ; R01 CA200859/CA/NCI NIH HHS/United States ; U01 CA196390/CA/NCI NIH HHS/United States ; }, mesh = {Computational Biology/*methods/statistics & numerical data ; Data Interpretation, Statistical ; Databases, Genetic ; Gene Expression Profiling/*methods/statistics & numerical data ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods/statistics & numerical data ; Humans ; MicroRNAs/genetics ; Neoplasms/genetics ; Precision Medicine/*methods ; Proteomics/methods ; }, abstract = {Data collected from omics technologies have revealed pervasive heterogeneity and stochasticity of molecular states within and between phenotypes. A prominent example of such heterogeneity occurs between genome-wide mRNA, microRNA, and methylation profiles from one individual tumor to another, even within a cancer subtype. However, current methods in bioinformatics, such as detecting differentially expressed genes or CpG sites, are population-based and therefore do not effectively model intersample diversity. Here we introduce a unified theory to quantify sample-level heterogeneity that is applicable to a single omics profile. Specifically, we simplify an omics profile to a digital representation based on the omics profiles from a set of samples from a reference or baseline population (e.g., normal tissues). The state of any subprofile (e.g., expression vector for a subset of genes) is said to be "divergent" if it lies outside the estimated support of the baseline distribution and is consequently interpreted as "dysregulated" relative to that baseline. We focus on two cases: single features (e.g., individual genes) and distinguished subsets (e.g., regulatory pathways). Notably, since the divergence analysis is at the individual sample level, dysregulation can be analyzed probabilistically; for example, one can estimate the probability that a gene or pathway is divergent in some population. Finally, the reduction in complexity facilitates a more "personalized" and biologically interpretable analysis of variation, as illustrated by experiments involving tissue characterization, disease detection and progression, and disease-pathway associations.}, } @article {pmid29666254, year = {2018}, author = {Fan, G and Dundas, CM and Graham, AJ and Lynd, NA and Keitz, BK}, title = {Shewanella oneidensis as a living electrode for controlled radical polymerization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4559-4564}, pmid = {29666254}, issn = {1091-6490}, support = {S10 OD021508/OD/NIH HHS/United States ; }, mesh = {Bacterial Proteins/metabolism ; Catalysis ; Electrodes/microbiology ; Electron Transport/*physiology ; Electrons ; Gene Expression Regulation, Bacterial/genetics ; Metabolic Engineering/*methods ; Metabolic Networks and Pathways ; Oxidation-Reduction ; Polymerization ; Shewanella/*metabolism/physiology ; }, abstract = {Metabolic engineering has facilitated the production of pharmaceuticals, fuels, and soft materials but is generally limited to optimizing well-defined metabolic pathways. We hypothesized that the reaction space available to metabolic engineering could be expanded by coupling extracellular electron transfer to the performance of an exogenous redox-active metal catalyst. Here we demonstrate that the electroactive bacterium Shewanella oneidensis can control the activity of a copper catalyst in atom-transfer radical polymerization (ATRP) via extracellular electron transfer. Using S. oneidensis, we achieved precise control over the molecular weight and polydispersity of a bioorthogonal polymer while similar organisms, such as Escherichia coli, showed no significant activity. We found that catalyst performance was a strong function of bacterial metabolism and specific electron transport proteins, both of which offer potential biological targets for future applications. Overall, our results suggest that manipulating extracellular electron transport pathways may be a general strategy for incorporating organometallic catalysis into the repertoire of metabolically controlled transformations.}, } @article {pmid29666253, year = {2018}, author = {Razafiarison, T and Holenstein, CN and Stauber, T and Jovic, M and Vertudes, E and Loparic, M and Kawecki, M and Bernard, L and Silvan, U and Snedeker, JG}, title = {Biomaterial surface energy-driven ligand assembly strongly regulates stem cell mechanosensitivity and fate on very soft substrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4631-4636}, pmid = {29666253}, issn = {1091-6490}, mesh = {Biocompatible Materials/metabolism ; Cell Adhesion ; Cell Differentiation ; Cell Proliferation ; Collagen/chemistry ; Elastic Modulus ; Humans ; Mechanotransduction, Cellular/*physiology ; Mesenchymal Stem Cells/*cytology/*physiology ; Signal Transduction ; Stem Cells ; Surface Tension ; }, abstract = {Although mechanisms of cell-material interaction and cellular mechanotransduction are increasingly understood, the mechanical insensitivity of mesenchymal cells to certain soft amorphous biomaterial substrates has remained largely unexplained. We reveal that surface energy-driven supramolecular ligand assembly can regulate mesenchymal stem cell (MSC) sensing of substrate mechanical compliance and subsequent cell fate. Human MSCs were cultured on collagen-coated hydrophobic polydimethylsiloxane (PDMS) and hydrophilic polyethylene-oxide-PDMS (PEO-PDMS) of a range of stiffnesses. Although cell contractility was similarly diminished on soft substrates of both types, cell spreading and osteogenic differentiation occurred only on soft PDMS and not hydrophilic PEO-PDMS (elastic modulus <1 kPa). Substrate surface energy yields distinct ligand topologies with accordingly distinct profiles of recruited transmembrane cell receptors and related focal adhesion signaling. These differences did not differentially regulate Rho-associated kinase activity, but nonetheless regulated both cell spreading and downstream differentiation.}, } @article {pmid29666252, year = {2018}, author = {Samant, PP and Prausnitz, MR}, title = {Mechanisms of sampling interstitial fluid from skin using a microneedle patch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4583-4588}, pmid = {29666252}, issn = {1091-6490}, support = {P30 ES019776/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Biomarkers/analysis ; Extracellular Fluid/*chemistry/cytology ; Female ; Humans ; Male ; Needles ; Skin/chemistry ; Specimen Handling/*methods ; Swine ; }, abstract = {Although interstitial fluid (ISF) contains biomarkers of physiological significance and medical interest, sampling of ISF for clinical applications has made limited impact due to a lack of simple, clinically useful techniques that collect more than nanoliter volumes of ISF. This study describes experimental and theoretical analysis of ISF transport from skin using microneedle (MN) patches and demonstrates collection of >1 µL of ISF within 20 min in pig cadaver skin and living human subjects using an optimized system. MN patches containing arrays of submillimeter solid, porous, or hollow needles were used to penetrate superficial skin layers and access ISF through micropores (µpores) formed upon insertion. Experimental studies in pig skin found that ISF collection depended on transport mechanism according to the rank order diffusion < capillary action < osmosis < pressure-driven convection, under the conditions studied. These findings were in agreement with independent theoretical modeling that considered transport within skin, across the interface between skin and µpores, and within µpores to the skin surface. This analysis indicated that the rate-limiting step for ISF sampling is transport through the dermis. Based on these studies and other considerations like safety and convenience for future clinical use, we designed an MN patch prototype to sample ISF using suction as the driving force. Using this approach, we collected ISF from human volunteers and identified the presence of biomarkers in the collected ISF. In this way, sampling ISF from skin using an MN patch could enable collection of ISF for use in research and medicine.}, } @article {pmid29666251, year = {2018}, author = {Fridley, JD and Wright, JP}, title = {Temperature accelerates the rate fields become forests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4702-4706}, pmid = {29666251}, issn = {1091-6490}, mesh = {Carbon/*metabolism ; *Climate Change ; *Forests ; *Models, Biological ; New England ; Trees/*growth & development ; }, abstract = {Secondary succession, the postdisturbance transition of herbaceous to woody-dominated ecosystems, occurs faster at lower latitudes with important ramifications for ecosystem processes. This pattern could be driven by the direct effect of temperature on tree growth; however, an alternative mechanism is tree-herb competition, which may be more intense in more fertile northern soils. We manipulated soil fertility and herbaceous species composition in identical experiments at six sites spanning the Eastern United States (30-43° N) and monitored the growth and survival of four early successional trees. Tree seedling mass 2 years after sowing was strongly associated with site differences in mean growing season temperature, regardless of species or soil treatment. The effect of temperature was twofold: seedlings grew faster in response to warmer site temperatures, but also due to the reduction of competitive interference from the herbaceous community, which was inhibited in warmer sites. Our results suggest that increasing temperatures will promote a faster transition of fields to forests in temperate ecosystems.}, } @article {pmid29666250, year = {2018}, author = {Occhetta, P and Pigeot, S and Rasponi, M and Dasen, B and Mehrkens, A and Ullrich, T and Kramer, I and Guth-Gundel, S and Barbero, A and Martin, I}, title = {Developmentally inspired programming of adult human mesenchymal stromal cells toward stable chondrogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4625-4630}, pmid = {29666250}, issn = {1091-6490}, mesh = {Activin Receptors, Type I/metabolism ; Adult ; Animals ; Bone Marrow Cells/metabolism ; Bone Morphogenetic Protein Receptors, Type I/metabolism ; Bone Morphogenetic Proteins/antagonists & inhibitors/metabolism ; Cartilage, Articular/metabolism ; Cell Differentiation/*drug effects ; Cells, Cultured ; Chondrocytes/metabolism ; Chondrogenesis/physiology ; Gene Expression Regulation/drug effects ; Humans ; Mesenchymal Stem Cells/metabolism/*physiology ; Mice ; Osteogenesis/drug effects ; Primary Cell Culture ; Signal Transduction/drug effects ; Tissue Engineering/*methods ; }, abstract = {It is generally accepted that adult human bone marrow-derived mesenchymal stromal cells (hMSCs) are default committed toward osteogenesis. Even when induced to chondrogenesis, hMSCs typically form hypertrophic cartilage that undergoes endochondral ossification. Because embryonic mesenchyme is obviously competent to generate phenotypically stable cartilage, it is questioned whether there is a correspondence between mesenchymal progenitor compartments during development and in adulthood. Here we tested whether forcing specific early events of articular cartilage development can program hMSC fate toward stable chondrogenesis. Inspired by recent findings that spatial restriction of bone morphogenetic protein (BMP) signaling guides embryonic progenitors toward articular cartilage formation, we hypothesized that selective inhibition of BMP drives the phenotypic stability of hMSC-derived chondrocytes. Two BMP type I receptor-biased kinase inhibitors were screened in a microfluidic platform for their time- and dose-dependent effect on hMSC chondrogenesis. The different receptor selectivity profile of tested compounds allowed demonstration that transient blockade of both ALK2 and ALK3 receptors, while permissive to hMSC cartilage formation, is necessary and sufficient to maintain a stable chondrocyte phenotype. Remarkably, even upon compound removal, hMSCs were no longer competent to undergo hypertrophy in vitro and endochondral ossification in vivo, indicating the onset of a constitutive change. Our findings demonstrate that adult hMSCs effectively share properties of embryonic mesenchyme in the formation of transient but also of stable cartilage. This opens potential pharmacological strategies to articular cartilage regeneration and more broadly indicates the relevance of developmentally inspired protocols to control the fate of adult progenitor cell systems.}, } @article {pmid29666249, year = {2018}, author = {Thakur, A and Hinnebusch, AG}, title = {eIF1 Loop 2 interactions with Met-tRNAi control the accuracy of start codon selection by the scanning preinitiation complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4159-E4168}, pmid = {29666249}, issn = {1091-6490}, mesh = {Codon, Initiator/*chemistry/genetics/metabolism ; Eukaryotic Initiation Factor-1/*chemistry/genetics/metabolism ; *Nucleic Acid Conformation ; *Peptide Chain Initiation, Translational ; Protein Structure, Secondary ; RNA, Fungal/*chemistry/genetics/metabolism ; RNA, Transfer, Met/*chemistry/genetics ; Ribosome Subunits, Small, Eukaryotic/chemistry/genetics/metabolism ; Saccharomyces cerevisiae/*chemistry/genetics/metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/genetics/metabolism ; }, abstract = {The eukaryotic 43S preinitiation complex (PIC), bearing initiator methionyl transfer RNA (Met-tRNAi) in a ternary complex (TC) with eukaryotic initiation factor 2 (eIF2)-GTP, scans the mRNA leader for an AUG codon in favorable context. AUG recognition evokes rearrangement from an open PIC conformation with TC in a "POUT" state to a closed conformation with TC more tightly bound in a "PIN" state. eIF1 binds to the 40S subunit and exerts a dual role of enhancing TC binding to the open PIC conformation while antagonizing the PIN state, necessitating eIF1 dissociation for start codon selection. Structures of reconstituted PICs reveal juxtaposition of eIF1 Loop 2 with the Met-tRNAi D loop in the PIN state and predict a distortion of Loop 2 from its conformation in the open complex to avoid a clash with Met-tRNAi We show that Ala substitutions in Loop 2 increase initiation at both near-cognate UUG codons and AUG codons in poor context. Consistently, the D71A-M74A double substitution stabilizes TC binding to 48S PICs reconstituted with mRNA harboring a UUG start codon, without affecting eIF1 affinity for 40S subunits. Relatively stronger effects were conferred by arginine substitutions; and no Loop 2 substitutions perturbed the rate of TC loading on scanning 40S subunits in vivo. Thus, Loop 2-D loop interactions specifically impede Met-tRNAi accommodation in the PIN state without influencing the POUT mode of TC binding; and Arg substitutions convert the Loop 2-tRNAi clash to an electrostatic attraction that stabilizes PIN and enhances selection of poor start codons in vivo.}, } @article {pmid29666248, year = {2018}, author = {Charlier, C and Alderson, TR and Courtney, JM and Ying, J and Anfinrud, P and Bax, A}, title = {Study of protein folding under native conditions by rapidly switching the hydrostatic pressure inside an NMR sample cell.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4169-E4178}, pmid = {29666248}, issn = {1091-6490}, support = {ZIA DK029046-10/NULL/Intramural NIH HHS/United States ; }, mesh = {Humans ; Hydrostatic Pressure ; *Nuclear Magnetic Resonance, Biomolecular ; *Protein Folding ; Ubiquitin/*chemistry ; }, abstract = {In general, small proteins rapidly fold on the timescale of milliseconds or less. For proteins with a substantial volume difference between the folded and unfolded states, their thermodynamic equilibrium can be altered by varying the hydrostatic pressure. Using a pressure-sensitized mutant of ubiquitin, we demonstrate that rapidly switching the pressure within an NMR sample cell enables study of the unfolded protein under native conditions and, vice versa, study of the native protein under denaturing conditions. This approach makes it possible to record 2D and 3D NMR spectra of the unfolded protein at atmospheric pressure, providing residue-specific information on the folding process. 15N and 13C chemical shifts measured immediately after dropping the pressure from 2.5 kbar (favoring unfolding) to 1 bar (native) are close to the random-coil chemical shifts observed for a large, disordered peptide fragment of the protein. However, 15N relaxation data show evidence for rapid exchange, on a ∼100-μs timescale, between the unfolded state and unstable, structured states that can be considered as failed folding events. The NMR data also provide direct evidence for parallel folding pathways, with approximately one-half of the protein molecules efficiently folding through an on-pathway kinetic intermediate, whereas the other half fold in a single step. At protein concentrations above ∼300 μM, oligomeric off-pathway intermediates compete with folding of the native state.}, } @article {pmid29666247, year = {2018}, author = {Kharouba, HM and Ehrlén, J and Gelman, A and Bolmgren, K and Allen, JM and Travers, SE and Wolkovich, EM}, title = {Global shifts in the phenological synchrony of species interactions over recent decades.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5211-5216}, pmid = {29666247}, issn = {1091-6490}, mesh = {Animals ; *Climate Change ; *Competitive Behavior ; *Ecosystem ; *Metamorphosis, Biological ; Models, Statistical ; *Phenotype ; Population Dynamics ; *Predatory Behavior ; Seasons ; Species Specificity ; Temperature ; Time Factors ; }, abstract = {Phenological responses to climate change (e.g., earlier leaf-out or egg hatch date) are now well documented and clearly linked to rising temperatures in recent decades. Such shifts in the phenologies of interacting species may lead to shifts in their synchrony, with cascading community and ecosystem consequences. To date, single-system studies have provided no clear picture, either finding synchrony shifts may be extremely prevalent [Mayor SJ, et al. (2017) Sci Rep 7:1902] or relatively uncommon [Iler AM, et al. (2013) Glob Chang Biol 19:2348-2359], suggesting that shifts toward asynchrony may be infrequent. A meta-analytic approach would provide insights into global trends and how they are linked to climate change. We compared phenological shifts among pairwise species interactions (e.g., predator-prey) using published long-term time-series data of phenological events from aquatic and terrestrial ecosystems across four continents since 1951 to determine whether recent climate change has led to overall shifts in synchrony. We show that the relative timing of key life cycle events of interacting species has changed significantly over the past 35 years. Further, by comparing the period before major climate change (pre-1980s) and after, we show that estimated changes in phenology and synchrony are greater in recent decades. However, there has been no consistent trend in the direction of these changes. Our findings show that there have been shifts in the timing of interacting species in recent decades; the next challenges are to improve our ability to predict the direction of change and understand the full consequences for communities and ecosystems.}, } @article {pmid29666246, year = {2018}, author = {Zhu, C and Beck, MV and Griffith, JD and Deshmukh, M and Dokholyan, NV}, title = {Large SOD1 aggregates, unlike trimeric SOD1, do not impact cell viability in a model of amyotrophic lateral sclerosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4661-4665}, pmid = {29666246}, issn = {1091-6490}, support = {R35 GM118331/GM/NIGMS NIH HHS/United States ; R01 GM114015/GM/NIGMS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 ES013773/ES/NIEHS NIH HHS/United States ; R01 GM031819/GM/NIGMS NIH HHS/United States ; R01 GM123247/GM/NIGMS NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*enzymology/genetics/pathology ; Cell Line, Tumor ; Cell Survival ; Humans ; *Models, Biological ; Protein Aggregation, Pathological/*enzymology/genetics ; Superoxide Dismutase/genetics/*metabolism ; Superoxide Dismutase-1/genetics/*metabolism ; }, abstract = {Aberrant accumulation of misfolded Cu, Zn superoxide dismutase (SOD1) is a hallmark of SOD1-associated amyotrophic lateral sclerosis (ALS), an invariably fatal neurodegenerative disease. While recent discovery of nonnative trimeric SOD1-associated neurotoxicity has suggested a potential pathway for motor neuron impairment, it is yet unknown whether large, insoluble aggregates are cytotoxic. Here we designed SOD1 mutations that specifically stabilize either the fibrillar form or the trimeric state of SOD1. The designed mutants display elevated populations of fibrils or trimers correspondingly, as demonstrated by gel filtration chromatography and electron microscopy. The trimer-stabilizing mutant, G147P, promoted cell death, even more potently in comparison with the aggressive ALS-associated mutants A4V and G93A. In contrast, the fibril-stabilizing mutants, N53I and D101I, positively impacted the survival of motor neuron-like cells. Hence, we conclude the SOD1 oligomer and not the mature form of aggregated fibril is critical for the neurotoxic effects in the model of ALS. The formation of large aggregates is in competition with trimer formation, suggesting that aggregation may be a protective mechanism against formation of toxic oligomeric intermediates.}, } @article {pmid29666245, year = {2018}, author = {Delanghe, JR and Speeckaert, MM and De Buyzere, ML}, title = {Iron status as a confounder in the gender gap in survival under extreme conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4148-E4149}, pmid = {29666245}, issn = {1091-6490}, mesh = {Epidemics ; Female ; Humans ; *Iron ; Male ; *Sex Factors ; Starvation ; *Survival ; }, } @article {pmid29666244, year = {2018}, author = {Darch, SE and Simoska, O and Fitzpatrick, M and Barraza, JP and Stevenson, KJ and Bonnecaze, RT and Shear, JB and Whiteley, M}, title = {Spatial determinants of quorum signaling in a Pseudomonas aeruginosa infection model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4779-4784}, pmid = {29666244}, issn = {1091-6490}, support = {R01 GM116547/GM/NIGMS NIH HHS/United States ; }, mesh = {Cystic Fibrosis/*metabolism/microbiology ; Humans ; *Models, Biological ; Pseudomonas Infections/*metabolism ; Pseudomonas aeruginosa/*metabolism ; Quorum Sensing/*physiology ; Signal Transduction/*physiology ; }, abstract = {Quorum sensing (QS) is a bacterial communication system that involves production and sensing of extracellular signals. In laboratory models, QS allows bacteria to monitor and respond to their own cell density and is critical for fitness. However, how QS proceeds in natural, spatially structured bacterial communities is not well understood, which significantly hampers our understanding of the emergent properties of natural communities. To address this gap, we assessed QS signaling in the opportunistic pathogen Pseudomonas aeruginosa in a cystic fibrosis (CF) lung infection model that recapitulates the biogeographical aspects of the natural human infection. In this model, P. aeruginosa grows as spatially organized, highly dense aggregates similar to those observed in the human CF lung. By combining this natural aggregate system with a micro-3D-printing platform that allows for confinement and precise spatial positioning of P. aeruginosa aggregates, we assessed the impact of aggregate size and spatial positioning on both intra- and interaggregate signaling. We discovered that aggregates containing ∼2,000 signal-producing P. aeruginosa were unable to signal neighboring aggregates, while those containing ≥5,000 cells signaled aggregates as far away as 176 µm. Not all aggregates within this "calling distance" responded, indicating that aggregates have differential sensitivities to signal. Overexpression of the signal receptor increased aggregate sensitivity to signal, suggesting that the ability of aggregates to respond is defined in part by receptor levels. These studies provide quantitative benchmark data for the impact of spatial arrangement and phenotypic heterogeneity on P. aeruginosa signaling in vivo.}, } @article {pmid29666243, year = {2018}, author = {Ezerskyte, M and Paredes, JA and Malvezzi, S and Burns, JA and Margison, GP and Olsson, M and Scicchitano, DA and Dreij, K}, title = {O6-methylguanine-induced transcriptional mutagenesis reduces p53 tumor-suppressor function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4731-4736}, pmid = {29666243}, issn = {1091-6490}, support = {R01 ES010581/ES/NIEHS NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Apoptosis/genetics ; Cell Line, Tumor ; Cell Transformation, Neoplastic/genetics/*metabolism/pathology ; DNA Repair ; G1 Phase Cell Cycle Checkpoints/genetics ; Guanine/*analogs & derivatives/metabolism ; Humans ; *Mutagenesis ; *Mutation, Missense ; S Phase Cell Cycle Checkpoints/genetics ; *Transcription, Genetic ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Altered protein function due to mutagenesis plays an important role in disease development. This is perhaps most evident in tumorigenesis and the associated loss or gain of function of tumor-suppressor genes and oncogenes. The extent to which lesion-induced transcriptional mutagenesis (TM) influences protein function and its contribution to the development of disease is not well understood. In this study, the impact of O6-methylguanine on the transcription fidelity of p53 and the subsequent effects on the protein's function as a regulator of cell death and cell-cycle arrest were examined in human cells. Levels of TM were determined by RNA-sequencing. In cells with active DNA repair, misincorporation of uridine opposite the lesion occurred in 0.14% of the transcripts and increased to 14.7% when repair by alkylguanine-DNA alkyltransferase was compromised. Expression of the dominant-negative p53 R248W mutant due to TM significantly reduced the transactivation of several established p53 target genes that mediate the tumor-suppressor function, including CDKN1A (p21) and BBC3 (PUMA). This resulted in deregulated signaling through the retinoblastoma protein and loss of G1/S cell-cycle checkpoint function. In addition, we observed impaired activation of apoptosis coupled to the reduction of the tumor-suppressor functions of p53. Taking these findings together, this work provides evidence that TM can induce phenotypic changes in mammalian cells that have important implications for the role of TM in tumorigenesis.}, } @article {pmid29666242, year = {2018}, author = {Austin, HP and Allen, MD and Donohoe, BS and Rorrer, NA and Kearns, FL and Silveira, RL and Pollard, BC and Dominick, G and Duman, R and El Omari, K and Mykhaylyk, V and Wagner, A and Michener, WE and Amore, A and Skaf, MS and Crowley, MF and Thorne, AW and Johnson, CW and Woodcock, HL and McGeehan, JE and Beckham, GT}, title = {Characterization and engineering of a plastic-degrading aromatic polyesterase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4350-E4357}, pmid = {29666242}, issn = {1091-6490}, support = {BB/P011918/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/*chemistry/genetics ; Burkholderiales/*enzymology/genetics ; Crystallography, X-Ray ; Esterases/*chemistry/genetics ; Polyethylene Terephthalates/*chemistry ; Protein Engineering ; Substrate Specificity ; }, abstract = {Poly(ethylene terephthalate) (PET) is one of the most abundantly produced synthetic polymers and is accumulating in the environment at a staggering rate as discarded packaging and textiles. The properties that make PET so useful also endow it with an alarming resistance to biodegradation, likely lasting centuries in the environment. Our collective reliance on PET and other plastics means that this buildup will continue unless solutions are found. Recently, a newly discovered bacterium, Ideonella sakaiensis 201-F6, was shown to exhibit the rare ability to grow on PET as a major carbon and energy source. Central to its PET biodegradation capability is a secreted PETase (PET-digesting enzyme). Here, we present a 0.92 Å resolution X-ray crystal structure of PETase, which reveals features common to both cutinases and lipases. PETase retains the ancestral α/β-hydrolase fold but exhibits a more open active-site cleft than homologous cutinases. By narrowing the binding cleft via mutation of two active-site residues to conserved amino acids in cutinases, we surprisingly observe improved PET degradation, suggesting that PETase is not fully optimized for crystalline PET degradation, despite presumably evolving in a PET-rich environment. Additionally, we show that PETase degrades another semiaromatic polyester, polyethylene-2,5-furandicarboxylate (PEF), which is an emerging, bioderived PET replacement with improved barrier properties. In contrast, PETase does not degrade aliphatic polyesters, suggesting that it is generally an aromatic polyesterase. These findings suggest that additional protein engineering to increase PETase performance is realistic and highlight the need for further developments of structure/activity relationships for biodegradation of synthetic polyesters.}, } @article {pmid29666241, year = {2018}, author = {Avetisyan, M and Rood, JE and Huerta Lopez, S and Sengupta, R and Wright-Jin, E and Dougherty, JD and Behrens, EM and Heuckeroth, RO}, title = {Muscularis macrophage development in the absence of an enteric nervous system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4696-4701}, pmid = {29666241}, issn = {1091-6490}, support = {OT2 OD023859/OD/NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; R01 DK087715/DK/NIDDK NIH HHS/United States ; R01 NS102272/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Communication/*physiology ; Enteric Nervous System/cytology/*embryology ; Fetus/cytology/*embryology ; *Intestines/cytology/embryology/innervation ; Macrophage Colony-Stimulating Factor/*metabolism ; Macrophages/cytology/*metabolism ; Mice ; Mice, Knockout ; Neurons/cytology/*metabolism ; }, abstract = {The nervous system of the bowel regulates the inflammatory phenotype of tissue resident muscularis macrophages (MM), and in adult mice, enteric neurons are the main local source of colony stimulating factor 1 (CSF1), a protein required for MM survival. Surprisingly, we find that during development MM colonize the bowel before enteric neurons. This calls into question the requirement for neuron-derived CSF1 for MM colonization of the bowel. To determine if intestinal innervation is required for MM development, we analyzed MM of neonatal Ret-/- (Ret KO) mice that have no enteric nervous system in small bowel or colon. We found normal numbers of well-patterned MM in Ret KO bowel. Similarly, the abundance and distribution of MM in aganglionic human colon obtained from Hirschsprung disease patients was normal. We also identify endothelial cells and interstitial cells of Cajal as the main sources of CSF1 in the developing bowel. Additionally, MM from neonatal Ret KOs do not differ from controls in baseline activation status or cytokine-production in response to lipopolysaccharide. Unexpectedly, these data demonstrate that the enteric nervous system is dispensable for MM colonization and patterning in the bowel, and suggest that modulatory interactions between MM and the bowel nervous system are established postnatally.}, } @article {pmid29666240, year = {2018}, author = {Tian, H and Hu, S and Cazelles, B and Chowell, G and Gao, L and Laine, M and Li, Y and Yang, H and Li, Y and Yang, Q and Tong, X and Huang, R and Bjornstad, ON and Xiao, H and Stenseth, NC}, title = {Urbanization prolongs hantavirus epidemics in cities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4707-4712}, pmid = {29666240}, issn = {1091-6490}, mesh = {Animals ; China ; *Databases, Factual ; Female ; *Hantavirus ; Hantavirus Infections/*epidemiology ; *Human Migration ; Humans ; Incidence ; Male ; *Urban Renewal ; Zoonoses/*epidemiology/virology ; }, abstract = {Urbanization and rural-urban migration are two factors driving global patterns of disease and mortality. There is significant concern about their potential impact on disease burden and the effectiveness of current control approaches. Few attempts have been made to increase our understanding of the relationship between urbanization and disease dynamics, although it is generally believed that urban living has contributed to reductions in communicable disease burden in industrialized countries. To investigate this relationship, we carried out spatiotemporal analyses using a 48-year-long dataset of hemorrhagic fever with renal syndrome incidence (HFRS; mainly caused by two serotypes of hantavirus in China: Hantaan virus and Seoul virus) and population movements in an important endemic area of south China during the period 1963-2010. Our findings indicate that epidemics coincide with urbanization, geographic expansion, and migrant movement over time. We found a biphasic inverted U-shaped relationship between HFRS incidence and urbanization, with various endemic turning points associated with economic growth rates in cities. Our results revealed the interrelatedness of urbanization, migration, and hantavirus epidemiology, potentially explaining why urbanizing cities with high economic growth exhibit extended epidemics. Our results also highlight contrasting effects of urbanization on zoonotic disease outbreaks during periods of economic development in China.}, } @article {pmid29666239, year = {2018}, author = {Barron, ATJ and Huang, J and Spang, RL and DeDeo, S}, title = {Individuals, institutions, and innovation in the debates of the French Revolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4607-4612}, pmid = {29666239}, issn = {1091-6490}, abstract = {The French Revolution brought principles of "liberty, equality, fraternity" to bear on the day-to-day challenges of governing what was then the largest country in Europe. Its experiments provided a model for future revolutions and democracies across the globe, but this first modern revolution had no model to follow. Using reconstructed transcripts of debates held in the Revolution's first parliament, we present a quantitative analysis of how this body managed innovation. We use information theory to track the creation, transmission, and destruction of word-use patterns across over 40,000 speeches and a thousand speakers. The parliament as a whole was biased toward the adoption of new patterns, but speakers' individual qualities could break these overall trends. Speakers on the left innovated at higher rates, while speakers on the right acted to preserve prior patterns. Key players such as Robespierre (on the left) and Abbé Maury (on the right) played information-processing roles emblematic of their politics. Newly created organizational functions-such as the Assembly president and committee chairs-had significant effects on debate outcomes, and a distinct transition appears midway through the parliament when committees, external to the debate process, gained new powers to "propose and dispose." Taken together, these quantitative results align with existing qualitative interpretations, but also reveal crucial information-processing dynamics that have hitherto been overlooked. Great orators had the public's attention, but deputies (mostly on the political left) who mastered the committee system gained new powers to shape revolutionary legislation.}, } @article {pmid29666238, year = {2018}, author = {Moore, SJ and MacDonald, JT and Wienecke, S and Ishwarbhai, A and Tsipa, A and Aw, R and Kylilis, N and Bell, DJ and McClymont, DW and Jensen, K and Polizzi, KM and Biedendieck, R and Freemont, PS}, title = {Rapid acquisition and model-based analysis of cell-free transcription-translation reactions from nonmodel bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4340-E4349}, pmid = {29666238}, issn = {1091-6490}, support = {BB/F017324/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Bacillus megaterium/chemistry/genetics/metabolism ; Cell-Free System/chemistry/metabolism ; *Models, Biological ; *Protein Biosynthesis ; *Transcription, Genetic ; }, abstract = {Native cell-free transcription-translation systems offer a rapid route to characterize the regulatory elements (promoters, transcription factors) for gene expression from nonmodel microbial hosts, which can be difficult to assess through traditional in vivo approaches. One such host, Bacillus megaterium, is a giant Gram-positive bacterium with potential biotechnology applications, although many of its regulatory elements remain uncharacterized. Here, we have developed a rapid automated platform for measuring and modeling in vitro cell-free reactions and have applied this to B. megaterium to quantify a range of ribosome binding site variants and previously uncharacterized endogenous constitutive and inducible promoters. To provide quantitative models for cell-free systems, we have also applied a Bayesian approach to infer ordinary differential equation model parameters by simultaneously using time-course data from multiple experimental conditions. Using this modeling framework, we were able to infer previously unknown transcription factor binding affinities and quantify the sharing of cell-free transcription-translation resources (energy, ribosomes, RNA polymerases, nucleotides, and amino acids) using a promoter competition experiment. This allows insights into resource limiting-factors in batch cell-free synthesis mode. Our combined automated and modeling platform allows for the rapid acquisition and model-based analysis of cell-free transcription-translation data from uncharacterized microbial cell hosts, as well as resource competition within cell-free systems, which potentially can be applied to a range of cell-free synthetic biology and biotechnology applications.}, } @article {pmid29666237, year = {2018}, author = {Schiro, KA and Ahmed, F and Giangrande, SE and Neelin, JD}, title = {GoAmazon2014/5 campaign points to deep-inflow approach to deep convection across scales.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4577-4582}, pmid = {29666237}, issn = {1091-6490}, abstract = {A substantial fraction of precipitation is associated with mesoscale convective systems (MCSs), which are currently poorly represented in climate models. Convective parameterizations are highly sensitive to the assumptions of an entraining plume model, in which high equivalent potential temperature air from the boundary layer is modified via turbulent entrainment. Here we show, using multiinstrument evidence from the Green Ocean Amazon field campaign (2014-2015; GoAmazon2014/5), that an empirically constrained weighting for inflow of environmental air based on radar wind profiler estimates of vertical velocity and mass flux yields a strong relationship between resulting buoyancy measures and precipitation statistics. This deep-inflow weighting has no free parameter for entrainment in the conventional sense, but to a leading approximation is simply a statement of the geometry of the inflow. The structure further suggests the weighting could consistently apply even for coherent inflow structures noted in field campaign studies for MCSs over tropical oceans. For radar precipitation retrievals averaged over climate model grid scales at the GoAmazon2014/5 site, the use of deep-inflow mixing yields a sharp increase in the probability and magnitude of precipitation with increasing buoyancy. Furthermore, this applies for both mesoscale and smaller-scale convection. Results from reanalysis and satellite data show that this holds more generally: Deep-inflow mixing yields a strong precipitation-buoyancy relation across the tropics. Deep-inflow mixing may thus circumvent inadequacies of current parameterizations while helping to bridge the gap toward representing mesoscale convection in climate models.}, } @article {pmid29666236, year = {2018}, author = {Buchman, A and Marshall, JM and Ostrovski, D and Yang, T and Akbari, OS}, title = {Synthetically engineered Medea gene drive system in the worldwide crop pest Drosophila suzukii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4725-4730}, pmid = {29666236}, issn = {1091-6490}, mesh = {Animals ; Drosophila/*genetics ; Drosophila Proteins/*genetics ; *Genetic Engineering ; *Pest Control, Biological ; Smad4 Protein/*genetics ; }, abstract = {Synthetic gene drive systems possess enormous potential to replace, alter, or suppress wild populations of significant disease vectors and crop pests; however, their utility in diverse populations remains to be demonstrated. Here, we report the creation of a synthetic Medea gene drive system in a major worldwide crop pest, Drosophila suzukii We demonstrate that this drive system, based on an engineered maternal "toxin" coupled with a linked embryonic "antidote," is capable of biasing Mendelian inheritance rates with up to 100% efficiency. However, we find that drive resistance, resulting from naturally occurring genetic variation and associated fitness costs, can be selected for and hinder the spread of such a drive. Despite this, our results suggest that this gene drive could maintain itself at high frequencies in a wild population and spread to fixation if either its fitness costs or toxin resistance were reduced, providing a clear path forward for developing future such systems in this pest.}, } @article {pmid29666235, year = {2018}, author = {Zhakhovsky, VV and Kryukov, AP and Levashov, VY and Shishkova, IN and Anisimov, SI}, title = {Mass and heat transfer between evaporation and condensation surfaces: Atomistic simulation and solution of Boltzmann kinetic equation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1714503115}, pmid = {29666235}, issn = {1091-6490}, abstract = {Boundary conditions required for numerical solution of the Boltzmann kinetic equation (BKE) for mass/heat transfer between evaporation and condensation surfaces are analyzed by comparison of BKE results with molecular dynamics (MD) simulations. Lennard-Jones potential with parameters corresponding to solid argon is used to simulate evaporation from the hot side, nonequilibrium vapor flow with a Knudsen number of about 0.02, and condensation on the cold side of the condensed phase. The equilibrium density of vapor obtained in MD simulation of phase coexistence is used in BKE calculations for consistency of BKE results with MD data. The collision cross-section is also adjusted to provide a thermal flux in vapor identical to that in MD. Our MD simulations of evaporation toward a nonreflective absorbing boundary show that the velocity distribution function (VDF) of evaporated atoms has the nearly semi-Maxwellian shape because the binding energy of atoms evaporated from the interphase layer between bulk phase and vapor is much smaller than the cohesive energy in the condensed phase. Indeed, the calculated temperature and density profiles within the interphase layer indicate that the averaged kinetic energy of atoms remains near-constant with decreasing density almost until the interphase edge. Using consistent BKE and MD methods, the profiles of gas density, mass velocity, and temperatures together with VDFs in a gap of many mean free paths between the evaporation and condensation surfaces are obtained and compared. We demonstrate that the best fit of BKE results with MD simulations can be achieved with the evaporation and condensation coefficients both close to unity.}, } @article {pmid29666234, year = {2018}, author = {Hirayama, S and Sugihara, M and Morito, D and Iemura, SI and Natsume, T and Murata, S and Nagata, K}, title = {Nuclear export of ubiquitinated proteins via the UBIN-POST system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4199-E4208}, pmid = {29666234}, issn = {1091-6490}, mesh = {Active Transport, Cell Nucleus/physiology ; Animals ; Carrier Proteins/genetics/*metabolism ; Cell Nucleus/genetics/*metabolism ; Cytosol/*metabolism ; HEK293 Cells ; HeLa Cells ; Human Umbilical Vein Endothelial Cells/cytology/*metabolism ; Humans ; Membrane Proteins/genetics/*metabolism ; Mice ; NIH 3T3 Cells ; Nuclear Proteins/genetics/*metabolism ; Ubiquitinated Proteins/genetics/*metabolism ; }, abstract = {Although mechanisms for protein homeostasis in the cytosol have been studied extensively, those in the nucleus remain largely unknown. Here, we identified that a protein complex mediates export of polyubiquitinated proteins from the nucleus to the cytosol. UBIN, a ubiquitin-associated (UBA) domain-containing protein, shuttled between the nucleus and the cytosol in a CRM1-dependent manner, despite the lack of intrinsic nuclear export signal (NES). Instead, the UBIN binding protein polyubiquitinated substrate transporter (POST) harboring an NES shuttled UBIN through nuclear pores. UBIN bound to polyubiquitin chain through its UBA domain, and the UBIN-POST complex exported them from the nucleus to the cytosol. Ubiquitinated proteins accumulated in the cytosol in response to proteasome inhibition, whereas cotreatment with CRM1 inhibitor led to their accumulation in the nucleus. Our results suggest that ubiquitinated proteins are exported from the nucleus to the cytosol in the UBIN-POST complex-dependent manner for the maintenance of nuclear protein homeostasis.}, } @article {pmid29666233, year = {2018}, author = {Maxwell, TM and Silva, LCR and Horwath, WR}, title = {Integrating effects of species composition and soil properties to predict shifts in montane forest carbon-water relations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4219-E4226}, pmid = {29666233}, issn = {1091-6490}, mesh = {California ; Carbon/*metabolism ; *Forests ; *Models, Biological ; *Soil ; Trees/*growth & development ; Water/*metabolism ; }, abstract = {This study was designed to address a major source of uncertainty pertaining to coupled carbon-water cycles in montane forest ecosystems. The Sierra Nevada of California was used as a model system to investigate connections between the physiological performance of trees and landscape patterns of forest carbon and water use. The intrinsic water-use efficiency (iWUE)-an index of CO2 fixed per unit of potential water lost via transpiration-of nine dominant species was determined in replicated transects along an ∼1,500-m elevation gradient, spanning a broad range of climatic conditions and soils derived from three different parent materials. Stable isotope ratios of carbon and oxygen measured at the leaf level were combined with field-based and remotely sensed metrics of stand productivity, revealing that variation in iWUE depends primarily on leaf traits (∼24% of the variability), followed by stand productivity (∼16% of the variability), climatic regime (∼13% of the variability), and soil development (∼12% of the variability). Significant interactions between species composition and soil properties proved useful to predict changes in forest carbon-water relations. On the basis of observed shifts in tree species composition, ongoing since the 1950s and intensified in recent years, an increase in water loss through transpiration (ranging from 10 to 60% depending on parent material) is now expected in mixed conifer forests throughout the region.}, } @article {pmid29666232, year = {2018}, author = {Powell Gray, B and Kelly, L and Ahrens, DP and Barry, AP and Kratschmer, C and Levy, M and Sullenger, BA}, title = {Tunable cytotoxic aptamer-drug conjugates for the treatment of prostate cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4761-4766}, pmid = {29666232}, issn = {1091-6490}, support = {P30 CA014236/CA/NCI NIH HHS/United States ; R21 CA157366/CA/NCI NIH HHS/United States ; R21 CA182330/CA/NCI NIH HHS/United States ; }, mesh = {Aminobenzoates/chemistry/*pharmacology ; Animals ; Antineoplastic Agents/chemistry/*pharmacology ; Aptamers, Nucleotide/chemistry/*pharmacology ; Delayed-Action Preparations/chemistry/pharmacology ; Humans ; Male ; Mice ; Mice, Nude ; Oligopeptides/chemistry/*pharmacology ; Prostatic Neoplasms/*drug therapy/metabolism/pathology ; Xenograft Model Antitumor Assays ; }, abstract = {Therapies that can eliminate both local and metastatic prostate tumor lesions while sparing normal organ tissue are desperately needed. With the goal of developing an improved drug-targeting strategy, we turned to a new class of targeted anticancer therapeutics: aptamers conjugated to highly toxic chemotherapeutics. Cell selection for aptamers with prostate cancer specificity yielded the E3 aptamer, which internalizes into prostate cancer cells without targeting normal prostate cells. Chemical conjugation of E3 to the drugs monomethyl auristatin E (MMAE) and monomethyl auristatin F (MMAF) yields a potent cytotoxic agent that efficiently kills prostate cancer cells in vitro but does not affect normal prostate epithelial cells. Importantly, the E3 aptamer targets tumors in vivo and treatment with the MMAF-E3 conjugate significantly inhibits prostate cancer growth in mice, demonstrating the in vivo utility of aptamer-drug conjugates. Additionally, we report the use of antidotes to block E3 aptamer-drug conjugate cytotoxicity, providing a safety switch in the unexpected event of normal cell killing in vivo.}, } @article {pmid29666231, year = {2018}, author = {Jia, Y and Xu, RG and Ren, X and Ewen-Campen, B and Rajakumar, R and Zirin, J and Yang-Zhou, D and Zhu, R and Wang, F and Mao, D and Peng, P and Qiao, HH and Wang, X and Liu, LP and Xu, B and Ji, JY and Liu, Q and Sun, J and Perrimon, N and Ni, JQ}, title = {Next-generation CRISPR/Cas9 transcriptional activation in Drosophila using flySAM.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4719-4724}, pmid = {29666231}, issn = {1091-6490}, support = {F32 GM113395/GM/NIGMS NIH HHS/United States ; R01 GM084947/GM/NIGMS NIH HHS/United States ; R24 OD021997/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Animals, Genetically Modified/genetics/metabolism ; *CRISPR-Cas Systems ; *Drosophila Proteins/biosynthesis/genetics ; Drosophila melanogaster ; Gene Expression Regulation/*genetics ; *Transcription Factors/biosynthesis/genetics ; }, abstract = {CRISPR/Cas9-based transcriptional activation (CRISPRa) has recently emerged as a powerful and scalable technique for systematic overexpression genetic analysis in Drosophila melanogaster We present flySAM, a potent tool for in vivo CRISPRa, which offers major improvements over existing strategies in terms of effectiveness, scalability, and ease of use. flySAM outperforms existing in vivo CRISPRa strategies and approximates phenotypes obtained using traditional Gal4-UAS overexpression. Moreover, because flySAM typically requires only a single sgRNA, it dramatically improves scalability. We use flySAM to demonstrate multiplexed CRISPRa, which has not been previously shown in vivo. In addition, we have simplified the experimental use of flySAM by creating a single vector encoding both the UAS:Cas9-activator and the sgRNA, allowing for inducible CRISPRa in a single genetic cross. flySAM will replace previous CRISPRa strategies as the basis of our growing genome-wide transgenic overexpression resource, TRiP-OE.}, } @article {pmid29666230, year = {2018}, author = {Žnidarič, M and Ljubotina, M}, title = {Interaction instability of localization in quasiperiodic systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4595-4600}, pmid = {29666230}, issn = {1091-6490}, abstract = {Integrable models form pillars of theoretical physics because they allow for full analytical understanding. Despite being rare, many realistic systems can be described by models that are close to integrable. Therefore, an important question is how small perturbations influence the behavior of solvable models. This is particularly true for many-body interacting quantum systems where no general theorems about their stability are known. Here, we show that no such theorem can exist by providing an explicit example of a one-dimensional many-body system in a quasiperiodic potential whose transport properties discontinuously change from localization to diffusion upon switching on interaction. This demonstrates an inherent instability of a possible many-body localization in a quasiperiodic potential at small interactions. We also show how the transport properties can be strongly modified by engineering potential at only a few lattice sites.}, } @article {pmid29666229, year = {2018}, author = {Xu, L and Naylor, D and Dong, Z and Simmons, T and Pierroz, G and Hixson, KK and Kim, YM and Zink, EM and Engbrecht, KM and Wang, Y and Gao, C and DeGraaf, S and Madera, MA and Sievert, JA and Hollingsworth, J and Birdseye, D and Scheller, HV and Hutmacher, R and Dahlberg, J and Jansson, C and Taylor, JW and Lemaux, PG and Coleman-Derr, D}, title = {Drought delays development of the sorghum root microbiome and enriches for monoderm bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4284-E4293}, pmid = {29666229}, issn = {1091-6490}, mesh = {ATP-Binding Cassette Transporters/genetics/metabolism ; *Bacteria/genetics/metabolism ; Bacterial Proteins/genetics/metabolism ; Cell Wall/genetics/metabolism ; Dehydration/metabolism/microbiology ; *Microbiota ; Plant Roots/growth & development/*microbiology ; RNA, Bacterial/genetics/metabolism ; RNA, Ribosomal, 16S/genetics/metabolism ; Sorghum/growth & development/*microbiology ; }, abstract = {Drought stress is a major obstacle to crop productivity, and the severity and frequency of drought are expected to increase in the coming century. Certain root-associated bacteria have been shown to mitigate the negative effects of drought stress on plant growth, and manipulation of the crop microbiome is an emerging strategy for overcoming drought stress in agricultural systems, yet the effect of drought on the development of the root microbiome is poorly understood. Through 16S rRNA amplicon and metatranscriptome sequencing, as well as root metabolomics, we demonstrate that drought delays the development of the early sorghum root microbiome and causes increased abundance and activity of monoderm bacteria, which lack an outer cell membrane and contain thick cell walls. Our data suggest that altered plant metabolism and increased activity of bacterial ATP-binding cassette (ABC) transporter genes are correlated with these shifts in community composition. Finally, inoculation experiments with monoderm isolates indicate that increased colonization of the root during drought can positively impact plant growth. Collectively, these results demonstrate the role that drought plays in restructuring the root microbiome and highlight the importance of temporal sampling when studying plant-associated microbiomes.}, } @article {pmid29666228, year = {2018}, author = {Ryu, JY and Kim, HU and Lee, SY}, title = {Deep learning improves prediction of drug-drug and drug-food interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4304-E4311}, pmid = {29666228}, issn = {1091-6490}, mesh = {Data Mining/*methods ; *Databases, Factual ; *Food-Drug Interactions ; Humans ; *Neural Networks (Computer) ; }, abstract = {Drug interactions, including drug-drug interactions (DDIs) and drug-food constituent interactions (DFIs), can trigger unexpected pharmacological effects, including adverse drug events (ADEs), with causal mechanisms often unknown. Several computational methods have been developed to better understand drug interactions, especially for DDIs. However, these methods do not provide sufficient details beyond the chance of DDI occurrence, or require detailed drug information often unavailable for DDI prediction. Here, we report development of a computational framework DeepDDI that uses names of drug-drug or drug-food constituent pairs and their structural information as inputs to accurately generate 86 important DDI types as outputs of human-readable sentences. DeepDDI uses deep neural network with its optimized prediction performance and predicts 86 DDI types with a mean accuracy of 92.4% using the DrugBank gold standard DDI dataset covering 192,284 DDIs contributed by 191,878 drug pairs. DeepDDI is used to suggest potential causal mechanisms for the reported ADEs of 9,284 drug pairs, and also predict alternative drug candidates for 62,707 drug pairs having negative health effects. Furthermore, DeepDDI is applied to 3,288,157 drug-food constituent pairs (2,159 approved drugs and 1,523 well-characterized food constituents) to predict DFIs. The effects of 256 food constituents on pharmacological effects of interacting drugs and bioactivities of 149 food constituents are predicted. These results suggest that DeepDDI can provide important information on drug prescription and even dietary suggestions while taking certain drugs and also guidelines during drug development.}, } @article {pmid29666227, year = {2018}, author = {Dosenovic, P and Kara, EE and Pettersson, AK and McGuire, AT and Gray, M and Hartweger, H and Thientosapol, ES and Stamatatos, L and Nussenzweig, MC}, title = {Anti-HIV-1 B cell responses are dependent on B cell precursor frequency and antigen-binding affinity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4743-4748}, pmid = {29666227}, issn = {1091-6490}, support = {R01 AI037526/AI/NIAID NIH HHS/United States ; UM1 AI100663/AI/NIAID NIH HHS/United States ; R01 AI081625/AI/NIAID NIH HHS/United States ; R01 AI104384/AI/NIAID NIH HHS/United States ; R37 AI037526/AI/NIAID NIH HHS/United States ; K99 AI127243/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Antibodies, Neutralizing/*immunology ; *Antibody Affinity ; B-Lymphocytes/*immunology ; HIV Antibodies/*immunology ; HIV Antigens/*immunology ; HIV-1/*immunology ; Mice ; Mice, Transgenic ; Precursor Cells, B-Lymphoid/*immunology ; }, abstract = {The discovery that humans can produce potent broadly neutralizing antibodies (bNAbs) to several different epitopes on the HIV-1 spike has reinvigorated efforts to develop an antibody-based HIV-1 vaccine. Antibody cloning from single cells revealed that nearly all bNAbs show unusual features that could help explain why it has not been possible to elicit them by traditional vaccination and instead would require a sequence of different immunogens. This idea is supported by experiments with genetically modified immunoglobulin (Ig) knock-in mice. Sequential immunization with a series of specifically designed immunogens was required to shepherd the development of bNAbs. However, knock-in mice contain superphysiologic numbers of bNAb precursor-expressing B cells, and therefore how these results can be translated to a more physiologic setting remains to be determined. Here we make use of adoptive transfer experiments using knock-in B cells that carry a synthetic intermediate in the pathway to anti-HIV-1 bNAb development to examine how the relationship between B cell receptor affinity and precursor frequency affects germinal center (GC) B cell recruitment and clonal expansion. Immunization with soluble HIV-1 antigens can recruit bNAb precursor B cells to the GC when there are as few as 10 such cells per mouse. However, at low precursor frequencies, the extent of clonal expansion is directly proportional to the affinity of the antigen for the B cell receptor, and recruitment to GCs is variable and dependent on recirculation.}, } @article {pmid29666226, year = {2018}, author = {Wang, X and Zhou, H and Chen, H and Jing, X and Zheng, W and Li, R and Sun, T and Liu, J and Fu, J and Huo, L and Li, YZ and Shen, Y and Ding, X and Müller, R and Bian, X and Zhang, Y}, title = {Discovery of recombinases enables genome mining of cryptic biosynthetic gene clusters in Burkholderiales species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4255-E4263}, pmid = {29666226}, issn = {1091-6490}, mesh = {Bacteriophages/*enzymology ; Burkholderia/*genetics ; *Genome, Bacterial ; *Multigene Family ; Recombinases/*chemistry ; Viral Proteins/*chemistry ; }, abstract = {Bacterial genomes encode numerous cryptic biosynthetic gene clusters (BGCs) that represent a largely untapped source of drugs or pesticides. Mining of the cryptic products is limited by the unavailability of streamlined genetic tools in native producers. Precise genome engineering using bacteriophage recombinases is particularly useful for genome mining. However, recombinases are usually host-specific. The genome-guided discovery of novel recombinases and their transient expression could boost cryptic BGC mining. Herein, we reported a genetic system employing Red recombinases from Burkholderiales strain DSM 7029 for efficient genome engineering in several Burkholderiales species that currently lack effective genetic tools. Using specialized recombinases-assisted in situ insertion of functional promoters, we successfully mined five cryptic nonribosomal peptide synthetase/polyketide synthase BGCs, two of which were silent. Two classes of lipopeptides, glidopeptins and rhizomides, were identified through extensive spectroscopic characterization. This recombinase expression strategy offers utility within other bacteria species, allowing bioprospecting for potentially scalable discovery of novel metabolites with attractive bioactivities.}, } @article {pmid29666225, year = {2018}, author = {Zarulli, V and Christensen, K and Vaupel, JW}, title = {Reply to Delanghe et al.: Iron status is not likely to play a key role in the gender survival gap under extreme conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4150}, pmid = {29666225}, issn = {1091-6490}, mesh = {Epidemics ; Female ; Humans ; *Iron ; Male ; *Sex Factors ; Starvation ; *Survival ; }, } @article {pmid29666224, year = {2018}, author = {Xi, B and Di, N and Liu, J and Zhang, R and Cao, Z}, title = {Hydrologic regulation of plant rooting depth: Pay attention to the widespread scenario with intense seasonal groundwater table fluctuation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3863-E3864}, pmid = {29666224}, issn = {1091-6490}, mesh = {Attention ; Groundwater ; *Hydrology ; Plant Roots ; *Seasons ; }, } @article {pmid29666223, year = {2018}, author = {Fan, Y and Miguez-Macho, G and Jobbágy, EG and Jackson, RB and Otero-Casal, C}, title = {Reply to Xi et al.: Water table fluctuation is well recognized and discussed in our study.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3865}, pmid = {29666223}, issn = {1091-6490}, mesh = {*Groundwater ; *Water ; }, } @article {pmid29665966, year = {2018}, author = {Lion, S and Metz, JAJ}, title = {Beyond R0 Maximisation: On Pathogen Evolution and Environmental Dimensions.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {458-473}, doi = {10.1016/j.tree.2018.02.004}, pmid = {29665966}, issn = {1872-8383}, mesh = {*Basic Reproduction Number ; *Biological Evolution ; *Host-Pathogen Interactions ; Models, Biological ; }, abstract = {A widespread tenet is that evolution of pathogens maximises their basic reproduction ratio, R0. The breakdown of this principle is typically discussed as exception. Here, we argue that a radically different stance is needed, based on evolutionarily stable strategy (ESS) arguments that take account of the 'dimension of the environmental feedback loop'. The R0 maximisation paradigm requires this feedback loop to be one-dimensional, which notably excludes pathogen diversification. By contrast, almost all realistic ecological ingredients of host-pathogen interactions (density-dependent mortality, multiple infections, limited cross-immunity, multiple transmission routes, host heterogeneity, and spatial structure) will lead to multidimensional feedbacks.}, } @article {pmid29665794, year = {2018}, author = {Pucher, A and Hash, CT and Wallace, JG and Han, S and Leiser, WL and Haussmann, BIG}, title = {Mapping a male-fertility restoration locus for the A4 cytoplasmic-genic male-sterility system in pearl millet using a genotyping-by-sequencing-based linkage map.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {65}, pmid = {29665794}, issn = {1471-2229}, support = {13.1432.7-001.00//Bundesministerium für Wirtschaftliche Zusammenarbeit und Entwicklung/ ; }, mesh = {Chromosome Mapping ; DNA, Plant/genetics ; Genetic Linkage/genetics/physiology ; Genotype ; Pennisetum/*genetics/*physiology ; Plant Infertility/genetics/*physiology ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; }, abstract = {BACKGROUND: Pearl millet (Pennisetum glaucum (L.) R. Br., syn. Cenchrus americanus (L.) R. Br) is an important cereal and fodder crop in hot and arid environments. There is great potential to improve pearl millet production through hybrid breeding. Cytoplasmic male sterility (CMS) and the corresponding nuclear fertility restoration / sterility maintenance genes (Rfs) are essential tools for economic hybrid seed production in pearl millet. Mapping the Rf genes of the A4 CMS system in pearl millet would enable more efficient introgression of both dominant male-fertility restoration alleles (Rf) and their recessive male-sterility maintenance counterparts (rf).

RESULTS: A high density linkage map based on single nucleotide polymorphism (SNP) markers was generated using an F2 mapping population and genotyping-by-sequencing (GBS). The parents of this cross were 'ICMA 02777' and 'ICMR 08888', which segregate for the A4 Rf locus. The linkage map consists of 460 SNP markers distributed mostly evenly and has a total length of 462 cM. The segregation ratio of male-fertile and male-sterile plants (3:1) based on pollen production (presence/absence) indicated monogenic dominant inheritance of male-fertility restoration. Correspondingly, a major quantitative trait locus (QTL) for pollen production was found on linkage group 2, with cross-validation showing a very high QTL occurrence (97%). The major QTL was confirmed using selfed seed set as phenotypic trait, though with a lower precision. However, these QTL explained only 14.5% and 9.9% of the phenotypic variance of pollen production and selfed seed set, respectively, which was below expectation. Two functional KASP markers were developed for the identified locus.

CONCLUSION: This study identified a major QTL for male-fertility restoration using a GBS-based linkage map and developed KASP markers which support high-throughput screening of the haploblock. This is a first step toward marker-assisted selection of A4 male-fertility restoration and male-sterility maintenance in pearl millet.}, } @article {pmid29665779, year = {2018}, author = {van den Akker, J and Mishne, G and Zimmer, AD and Zhou, AY}, title = {A machine learning model to determine the accuracy of variant calls in capture-based next generation sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {263}, pmid = {29665779}, issn = {1471-2164}, mesh = {Base Sequence ; Genetic Variation ; *High-Throughput Nucleotide Sequencing ; *Machine Learning ; *Models, Statistical ; }, abstract = {BACKGROUND: Next generation sequencing (NGS) has become a common technology for clinical genetic tests. The quality of NGS calls varies widely and is influenced by features like reference sequence characteristics, read depth, and mapping accuracy. With recent advances in NGS technology and software tools, the majority of variants called using NGS alone are in fact accurate and reliable. However, a small subset of difficult-to-call variants that still do require orthogonal confirmation exist. For this reason, many clinical laboratories confirm NGS results using orthogonal technologies such as Sanger sequencing. Here, we report the development of a deterministic machine-learning-based model to differentiate between these two types of variant calls: those that do not require confirmation using an orthogonal technology (high confidence), and those that require additional quality testing (low confidence). This approach allows reliable NGS-based calling in a clinical setting by identifying the few important variant calls that require orthogonal confirmation.

RESULTS: We developed and tested the model using a set of 7179 variants identified by a targeted NGS panel and re-tested by Sanger sequencing. The model incorporated several signals of sequence characteristics and call quality to determine if a variant was identified at high or low confidence. The model was tuned to eliminate false positives, defined as variants that were called by NGS but not confirmed by Sanger sequencing. The model achieved very high accuracy: 99.4% (95% confidence interval: +/- 0.03%). It categorized 92.2% (6622/7179) of the variants as high confidence, and 100% of these were confirmed to be present by Sanger sequencing. Among the variants that were categorized as low confidence, defined as NGS calls of low quality that are likely to be artifacts, 92.1% (513/557) were found to be not present by Sanger sequencing.

CONCLUSIONS: This work shows that NGS data contains sufficient characteristics for a machine-learning-based model to differentiate low from high confidence variants. Additionally, it reveals the importance of incorporating site-specific features as well as variant call features in such a model.}, } @article {pmid29665776, year = {2018}, author = {MacMillan, CP and Birke, H and Chuah, A and Brill, E and Tsuji, Y and Ralph, J and Dennis, ES and Llewellyn, D and Pettolino, FA}, title = {Correction to: Tissue and cell-specific transcriptomes in cotton reveal the subtleties of gene regulation underlying the diversity of plant secondary cell walls.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {261}, pmid = {29665776}, issn = {1471-2164}, abstract = {Upon publication of the original article [1], the authors had flagged that Fig. 1 had been published twice, as both Fig. 1 and Additional file 3.}, } @article {pmid29665774, year = {2018}, author = {Zhao, H and Kuang, L and Wang, L and Ping, P and Xuan, Z and Pei, T and Wu, Z}, title = {Prediction of microRNA-disease associations based on distance correlation set.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {141}, pmid = {29665774}, issn = {1471-2105}, support = {No.61640210//National Natural Science Foundation of China/International ; No.61672447//National Natural Science Foundation of China/International ; No. NGII20160305//CERNET Next Generation Internet Technology Innovation Project/International ; No.2017JJ5036//Science & Education Joint Project of Hunan Natural Science Foundation/International ; No.11KZ|KZ03051//Upgrading Project of Industry-University- Research of Xiangtan University/International ; }, mesh = {Algorithms ; Area Under Curve ; Computational Biology ; Databases, Genetic ; *Genetic Predisposition to Disease ; Humans ; Male ; MicroRNAs/*genetics/metabolism ; Models, Genetic ; Neoplasms/genetics ; RNA, Long Noncoding/genetics/metabolism ; }, abstract = {BACKGROUND: Recently, numerous laboratory studies have indicated that many microRNAs (miRNAs) are involved in and associated with human diseases and can serve as potential biomarkers and drug targets. Therefore, developing effective computational models for the prediction of novel associations between diseases and miRNAs could be beneficial for achieving an understanding of disease mechanisms at the miRNA level and the interactions between diseases and miRNAs at the disease level. Thus far, only a few miRNA-disease association pairs are known, and models analyzing miRNA-disease associations based on lncRNA are limited.

RESULTS: In this study, a new computational method based on a distance correlation set is developed to predict miRNA-disease associations (DCSMDA) by integrating known lncRNA-disease associations, known miRNA-lncRNA associations, disease semantic similarity, and various lncRNA and disease similarity measures. The novelty of DCSMDA is due to the construction of a miRNA-lncRNA-disease network, which reveals that DCSMDA can be applied to predict potential lncRNA-disease associations without requiring any known miRNA-disease associations. Although the implementation of DCSMDA does not require known disease-miRNA associations, the area under curve is 0.8155 in the leave-one-out cross validation. Furthermore, DCSMDA was implemented in case studies of prostatic neoplasms, lung neoplasms and leukaemia, and of the top 10 predicted associations, 10, 9 and 9 associations, respectively, were separately verified in other independent studies and biological experimental studies. In addition, 10 of the 10 (100%) associations predicted by DCSMDA were supported by recent bioinformatical studies.

CONCLUSIONS: According to the simulation results, DCSMDA can be a great addition to the biomedical research field.}, } @article {pmid29665773, year = {2018}, author = {He, Z and Yu, Q}, title = {Identification and characterization of functional modules reflecting transcriptome transition during human neuron maturation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {262}, pmid = {29665773}, issn = {1471-2164}, support = {91331203//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Humans ; Mice ; Neurogenesis/genetics ; Neurons/*cytology/metabolism ; Protein Interaction Maps ; *Transcriptome ; }, abstract = {BACKGROUND: Neuron maturation is a critical process in neurogenesis, during which neurons gain their morphological, electrophysiological and molecular characteristics for their functions as the central components of the nervous system.

RESULTS: To better understand the molecular changes during this process, we combined the protein-protein interaction network and public single cell RNA-seq data of mature and immature neurons to identify functional modules relevant to the neuron maturation process in humans. Among the 109 functional modules in total, 33 showed significant gene expression level changes (discriminating modules) which participate in varied functions including energy consumption, synaptic functions and housekeeping functions such as translation and splicing. Based on the identified modules, we trained a neuron maturity index (NMI) model for the quantification of maturation states of single neurons or purified bulk neurons. Applied to multiple single neuron transcriptome data sets of neuron development in humans and mice, the NMI model made estimation of neuron maturity states which were significantly correlated with the neuron maturation trajectories in both species, implying the reproducibility and conservation of the identified transcriptome transition.

CONCLUSION: We identified 33 discriminating modules whose activities were significantly correlated with single neuron maturity states, which may play important roles in the neuron maturation process.}, } @article {pmid29665771, year = {2018}, author = {Fumey, J and Hinaux, H and Noirot, C and Thermes, C and Rétaux, S and Casane, D}, title = {Evidence for late Pleistocene origin of Astyanax mexicanus cavefish.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {43}, pmid = {29665771}, issn = {1471-2148}, support = {BLINDTEST//Agence Nationale de la Recherche/International ; }, mesh = {Adaptation, Biological/*genetics ; Animals ; *Caves ; Characidae/anatomy & histology/classification/*genetics ; DNA, Mitochondrial/analysis/genetics ; Evolution, Molecular ; *Genetic Variation ; History, Ancient ; Mexico ; New Mexico ; Phylogeny ; Polymorphism, Single Nucleotide ; Texas ; }, abstract = {BACKGROUND: Cavefish populations belonging to the Mexican tetra species Astyanax mexicanus are outstanding models to study the tempo and mode of adaptation to a radical environmental change. They are currently assigned to two main groups, the so-called "old" and "new" lineages, which would have populated several caves independently and at different times. However, we do not have yet accurate estimations of the time frames of evolution of these populations.

RESULTS: We reanalyzed the geographic distribution of mitochondrial and nuclear DNA polymorphisms and we found that these data do not support the existence of two cavefish lineages. Using IMa2, a program that allows dating population divergence in addition to demographic parameters, we found that microsatellite polymorphism strongly supports a very recent origin of cave populations (< 20,000 years). We identified a large number of single-nucleotide polymorphisms (SNPs) in transcript sequences of pools of embryos (Pool-seq) belonging to Pachón cave population and a surface population from Texas. Based on summary statistics that can be computed with this SNP data set together with simulations of evolution of SNP polymorphisms in two recently isolated populations, we looked for sets of demographic parameters that allow the computation of summary statistics with simulated populations that are similar to the ones with the sampled populations. In most simulations for which we could find a good fit between the summary statistics of observed and simulated data, the best fit occurred when the divergence between simulated populations was less than 30,000 years.

CONCLUSIONS: Although it is often assumed that some cave populations have a very ancient origin, a recent origin of these populations is strongly supported by our analyses of independent sets of nuclear DNA polymorphism. Moreover, the observation of two divergent haplogroups of mitochondrial and nuclear genes with different geographic distributions support a recent admixture of two divergent surface populations, before the isolation of cave populations. If cave populations are indeed only several thousand years old, many phenotypic changes observed in cavefish would thus have mainly involved the fixation of genetic variants present in surface fish populations and within a very short period of time.}, } @article {pmid29665025, year = {2018}, author = {Minias, P and Pikus, E and Whittingham, LA and Dunn, PO}, title = {A global analysis of selection at the avian MHC.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1278-1293}, doi = {10.1111/evo.13490}, pmid = {29665025}, issn = {1558-5646}, abstract = {Recent advancements in sequencing technology have resulted in rapid progress in the study of the major histocompatibility complex (MHC) in non-model avian species. Here, we analyze a global dataset of avian MHC class I and class II sequences (ca. 11,000 sequences from over 250 species) to gain insight into the processes that govern macroevolution of MHC genes in birds. Analysis of substitution rates revealed striking differences in the patterns of diversifying selection between passerine and non-passerine birds. Non-passerines showed stronger selection at MHC class II, which is primarily involved in recognition of extracellular pathogens, while passerines showed stronger selection at MHC class I, which is involved in recognition of intracellular pathogens. Positions of positively selected amino-acid residues showed marked discrepancies with peptide-binding residues (PBRs) of human MHC molecules, suggesting that using a human classification of PBRs to assess selection patterns at the avian MHC may be unjustified. Finally, our analysis provided evidence that indel mutations can make a substantial contribution to adaptive variation at the avian MHC.}, } @article {pmid29665015, year = {2018}, author = {Leinweber, A and Weigert, M and Kümmerli, R}, title = {The bacterium Pseudomonas aeruginosa senses and gradually responds to interspecific competition for iron.}, journal = {Evolution; international journal of organic evolution}, volume = {}, number = {}, pages = {}, doi = {10.1111/evo.13491}, pmid = {29665015}, issn = {1558-5646}, abstract = {Phenotypic plasticity in response to competition is a well-described phenomenon in higher organisms. Here, we show that also bacteria have the ability to sense the presence of competitors and mount fine-tuned responses to match prevailing levels of competition. In our experiments, we studied interspecific competition for iron between the bacterium Pseudomonas aeruginosa (PA) and its competitor Burkholderia cenocepacia (BC). We focused on the ability of PA to phenotypically adjust the production of pyoverdine, an iron-scavenging siderophore. We found that PA upregulates pyoverdine production early on during competition under condition of low iron availability. This plastic upregulation was fine-tuned in response to the level of competition imposed by BC, and seems to confer a relative fitness benefit to PA in the form of an earlier initiation of growth. At later time points, however, PA showed reduced growth in mixed compared to monoculture, suggesting that competitive responses are costly. Altogether, our results demonstrate that phenotypic plasticity in siderophore production plays an important role in interspecific competition for iron. Upregulating siderophore production may be a powerful strategy to lock iron away from competing species, and to reserve this nutrient for strain members possessing the compatible receptor for uptake.}, } @article {pmid29664475, year = {2018}, author = {Harvey, JA and van den Berg, D and Ellers, J and Kampen, R and Crowther, TW and Roessingh, P and Verheggen, B and Nuijten, RJM and Post, E and Lewandowsky, S and Stirling, I and Balgopal, M and Amstrup, SC and Mann, ME}, title = {Corrigendum: Internet Blogs, Polar Bears, and Climate-Change Denial by Proxy.}, journal = {Bioscience}, volume = {68}, number = {4}, pages = {237}, doi = {10.1093/biosci/biy033}, pmid = {29664475}, issn = {0006-3568}, abstract = {[This corrects the article DOI: 10.1093/biosci/bix133.].}, } @article {pmid29664363, year = {2018}, author = {Lu, LY and Chen, LL and Xing, ZY and Hu, T and Lu, JS and Huang, X}, title = {Paenibacillus yanchengensis sp. nov., isolated from farmland soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1902-1906}, doi = {10.1099/ijsem.0.002763}, pmid = {29664363}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; *Farms ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sodium Chloride/analysis ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-variable, short-rod-shaped, motile, spore-forming, strictly aerobic and alkaliresistant bacterium, designed strain J-3T, was isolated from farmland soil sampled in Yancheng city, Jiangsu province, China. Optimal growth occurred at 30 °C, pH 7.0-8.0 and 0.5 % (w/v) NaCl. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain J-3T was most closely related to Paenibacillusripae HZ1T (96.8 %), followed by Paenibacillussputi KIT00200-70066-1T (94.7 %). The major cellular fatty acids were anteiso-C15 : 0 and C16 : 0. The dominant respiratory quinone was menaquinone-7 and the DNA G+C content was 41.2 mol%. The major polar lipids of strain J-3T were aminolipid, phospholipid, diphosphatidylglycerol, phosphatidylglycerol, phosphoaminolipid and phosphatidylethanolamine. The diagnostic diamino acid of the cell-wall peptidoglycan was meso-diaminopimelic acid. On the basis of genotypic and phenotypic data, strain J-3T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus yanchengensis sp. nov. is proposed. The type strain is J-3T (=KCTC 33926T=CGMCC 1.16455T).}, } @article {pmid29664362, year = {2018}, author = {Castro, DJ and Cerezo, I and Sampedro, I and Martínez-Checa, F}, title = {Roseovarius ramblicola sp. nov., a moderately halophilic bacterium isolated from saline soil in Spain.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1851-1856}, doi = {10.1099/ijsem.0.002744}, pmid = {29664362}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; *Salinity ; Sequence Analysis, DNA ; Soil ; *Soil Microbiology ; Spain ; Ubiquinone/chemistry ; }, abstract = {Strain D15T was isolated from a soil sample taken from Rambla Salada (Murcia), south-eastern Spain, by using the dilution-to-extinction method. The strain, a Gram-stain-negative aerobic bacteria, is non-motile, ovoid- or rod-shaped, catalase- and oxidase-positive, and grows at NaCl concentrations within the range 0.5-10 % (w/v) [optimum 3 % (w/v)], at 5-30 °C (optimum 28 °C) and at pH 6-9 (optimum pH 7.0). The 16S rRNA gene sequence indicates that it belongs to the genus Roseovarius in the class Alphaproteobacteria. Its closest relatives are Roseovarius tolerans EL-172T and Roseovarius azorensis SSW084T, to which the strain shows 16S rRNA gene-sequence similarity values of 96.1 and 95.3 %, respectively. The DNA G+C content is 63 mol%. The major fatty acids (>5 % of the total fatty acids) of strain D15T are C18 : 1ω7c, C16 : 0 and C12 : 0. The only detected isoprenoid quinone of strain D15T is ubiquinone 10 (Q-10). The polar lipid profile contains phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, aminolipid and three polar lipids. Based on the phylogenetic, genotypic, phenotypic and chemotaxonomic data, the strain represents a novel species of the genus Roseovarius, for which the name Roseovarius ramblicola sp. nov. is proposed. Strain D15T (=CECT 9424=LMG 30322) is the type strain.}, } @article {pmid29664361, year = {2018}, author = {Akter, S and Shin, MK}, title = {Pseudaeromonas paramecii sp. nov., isolated from the ciliate Paramecium caudatum and emendation of the genus Pseudaeromonas.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002746}, pmid = {29664361}, issn = {1466-5034}, abstract = {A Gram-stain-negative, oxidase-negative and catalase-negative, motile, rod-shaped bacterial strain, designated PCS8T, hosted by the ciliate Paramecium caudatum was investigated by using a polyphasic approach. Strain PCS8T was observed to be able to grow at 12-44 °C (optimum, 36-37 °C), at pH 6.0-10.0 (optimum, 7.0) and in the presence of 0-3 % NaCl (optimum, 1-2 %). It could hydrolyse starch and aesculin and produce acid from d-sorbitol, myo-inositol, glycerol and l-rhamnose. The sequence similarity of the new isolate was 96.9 % with respect to Pseudaeromonas pectinilytica and 96.3 % with respect to Pseudaeromonas sharmana. Phylogenetically, strain PCS8T falls within the cluster comprising the Pseudaeromonas species. The predominant cellular fatty acids of strain PCS8T were C16 : 0 (35.8 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c; 35.1 %) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 10.8 %). This novel strain also contained various fatty acids that are not detected in other members of the genus Pseudaeromonas, such as C16 : 0 3-OH, C18 : 1ω9c and summed feature 5 (C18 : 2ω6,9c and/or C18 : 0 ante). Strain PCS8T contained ubiquinone-8 as the sole respiratory quinone and phosphatidylethanolamine and phosphatidylglycerol as major polar lipids. The G+C content of the genomic DNA of the type strain was 66.5 mol%. Based on the distinct phenotypic, phylogenetic, chemotaxonomic and G+C content results, strain PCS8T represents a currently undescribed species within the genus Pseudaeromonas in the family Aeromonadaceae, for which we suggest the name Pseudaeromonas paramecii sp. nov. with the type strain PCS8T (=KCTC 62038T=JCM 32226T). An emended description of the genus Pseudaeromonas is also provided.}, } @article {pmid29663630, year = {2018}, author = {Albuquerque, TAF and Drummond do Val, L and Doherty, A and de Magalhães, JP}, title = {From humans to hydra: patterns of cancer across the tree of life.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1715-1734}, pmid = {29663630}, issn = {1469-185X}, support = {//Wellcome Trust/United Kingdom ; 104978/Z/14/Z//Wellcome Trust/United Kingdom ; }, abstract = {Cancer is a disease of multicellularity; it originates when cells become dysregulated due to mutations and grow out of control, invading other tissues and provoking discomfort, disability, and eventually death. Human life expectancy has greatly increased in the last two centuries, and consequently so has the incidence of cancer. However, how cancer patterns in humans compare to those of other species remains largely unknown. In this review, we search for clues about cancer and its evolutionary underpinnings across the tree of life. We discuss data from a wide range of species, drawing comparisons with humans when adequate, and interpret our findings from an evolutionary perspective. We conclude that certain cancers are uniquely common in humans, such as lung, prostate, and testicular cancer; while others are common across many species. Lymphomas appear in almost every animal analysed, including in young animals, which may be related to pathogens imposing selection on the immune system. Cancers unique to humans may be due to our modern environment or may be evolutionary accidents: random events in the evolution of our species. Finally, we find that cancer-resistant animals such as whales and mole-rats have evolved cellular mechanisms that help them avoid neoplasia, and we argue that there are multiple natural routes to cancer resistance.}, } @article {pmid29663622, year = {2018}, author = {Vorburger, C and Perlman, SJ}, title = {The role of defensive symbionts in host-parasite coevolution.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {4}, pages = {1747-1764}, doi = {10.1111/brv.12417}, pmid = {29663622}, issn = {1469-185X}, support = {CRSII3_154396//Swiss National Science Foundation/Switzerland ; }, abstract = {Understanding the coevolution of hosts and parasites is a long-standing goal of evolutionary biology. There is a well-developed theoretical framework to describe the evolution of host-parasite interactions under the assumption of direct, two-species interactions, which can result in arms race dynamics or sustained genotype fluctuations driven by negative frequency dependence (Red Queen dynamics). However, many hosts rely on symbionts for defence against parasites. Whilst the ubiquity of defensive symbionts and their potential importance for disease control are increasingly recognized, there is still a gap in our understanding of how symbionts mediate or possibly take part in host-parasite coevolution. Herein we address this question by synthesizing information already available from theoretical and empirical studies. First, we briefly introduce current hypotheses on how defensive mutualisms evolved from more parasitic relationships and highlight exciting new experimental evidence showing that this can occur very rapidly. We go on to show that defensive symbionts influence virtually all important determinants of coevolutionary dynamics, namely the variation in host resistance available to selection by parasites, the specificity of host resistance, and the trade-off structure between host resistance and other components of fitness. In light of these findings, we turn to the limited theory and experiments available for such three-species interactions to assess the role of defensive symbionts in host-parasite coevolution. Specifically, we discuss under which conditions the defensive symbiont may take over from the host the reciprocal adaptation with parasites and undergo its own selection dynamics, thereby altering or relaxing selection on the hosts' own immune defences. Finally, we address potential effects of defensive symbionts on the evolution of parasite virulence. This is an important problem for which there is no single, clear-cut prediction. The selection on parasite virulence resulting from the presence of defensive symbionts in their hosts will depend on the underlying mechanism of defence. We identify the evolutionary predictions for different functional categories of symbiont-conferred resistance and we evaluate the empirical literature for supporting evidence. We end this review with outstanding questions and promising avenues for future research to improve our understanding of symbiont-mediated coevolution between hosts and parasites.}, } @article {pmid29663064, year = {2018}, author = {Soukup, V and Mrstakova, S and Kozmik, Z}, title = {Asymmetric pitx2 expression in medaka epithalamus is regulated by nodal signaling through an intronic enhancer.}, journal = {Development genes and evolution}, volume = {228}, number = {2}, pages = {131-139}, pmid = {29663064}, issn = {1432-041X}, support = {14-20839P//Grantová Agentura České Republiky (CZ)/International ; RVO68378050//Institute of Molecular Genetics of the Czech Academy of Sciences/International ; LO1419//Ministerstvo Školství, Mládeže a Tělovýchovy (CZ)/International ; }, mesh = {Animals ; Binding Sites ; Embryo, Nonmammalian/cytology/metabolism ; *Enhancer Elements, Genetic ; Epithalamus/embryology/*metabolism ; Forkhead Transcription Factors/genetics/metabolism ; Functional Laterality ; *Gene Expression Regulation, Developmental ; Green Fluorescent Proteins/genetics/metabolism ; Homeodomain Proteins/genetics/*metabolism ; *Introns ; Mesoderm/embryology/metabolism ; Nodal Protein/genetics/*metabolism ; Oryzias/*embryology/*genetics ; Signal Transduction ; Transcription Factors/genetics/*metabolism ; Transgenes/genetics ; }, abstract = {The epithalamic region of fishes shows prominent left-right asymmetries that are executed by nodal signaling upstream of the asymmetry-determining transcription factor pitx2. Previous reports have identified that nodal controls the left-sided pitx2 expression in the lateral plate mesoderm through an enhancer present in the last intron of this gene. However, whether similar regulation occurs also in the case of epithalamic asymmetry is currently unresolved. Here, we address some of the cis-regulatory information that control asymmetric pitx2 expression in epithalamus by presenting a Tg(pitx2:EGFP) 116-17 transgenic medaka model, which expresses enhanced green fluorescent protein (EGFP) under control of an intronic enhancer. We show that this transgene recapitulates epithalamic expression of the endogenous pitx2 and that it responds to nodal signaling inhibition. Further, we identify that three foxh1-binding sites present in this enhancer modulate expression of the transgene and that the second site is absolutely necessary for the left-sided epithalamic expression while the other two sites may have subtler regulative roles. We provide evidence that left-sided epithalamic pitx2 expression is controlled through an enhancer present in the last intron of this gene and that the regulatory logic underlying asymmetric pitx2 expression is shared between epithalamic and lateral plate mesoderm regions.}, } @article {pmid29662297, year = {2018}, author = {García-Calvo, R and Guisado, JL and Diaz-Del-Rio, F and Córdoba, A and Jiménez-Morales, F}, title = {Graphics Processing Unit-Enhanced Genetic Algorithms for Solving the Temporal Dynamics of Gene Regulatory Networks.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318767889}, pmid = {29662297}, issn = {1176-9343}, abstract = {Understanding the regulation of gene expression is one of the key problems in current biology. A promising method for that purpose is the determination of the temporal dynamics between known initial and ending network states, by using simple acting rules. The huge amount of rule combinations and the nonlinear inherent nature of the problem make genetic algorithms an excellent candidate for finding optimal solutions. As this is a computationally intensive problem that needs long runtimes in conventional architectures for realistic network sizes, it is fundamental to accelerate this task. In this article, we study how to develop efficient parallel implementations of this method for the fine-grained parallel architecture of graphics processing units (GPUs) using the compute unified device architecture (CUDA) platform. An exhaustive and methodical study of various parallel genetic algorithm schemes-master-slave, island, cellular, and hybrid models, and various individual selection methods (roulette, elitist)-is carried out for this problem. Several procedures that optimize the use of the GPU's resources are presented. We conclude that the implementation that produces better results (both from the performance and the genetic algorithm fitness perspectives) is simulating a few thousands of individuals grouped in a few islands using elitist selection. This model comprises 2 mighty factors for discovering the best solutions: finding good individuals in a short number of generations, and introducing genetic diversity via a relatively frequent and numerous migration. As a result, we have even found the optimal solution for the analyzed gene regulatory network (GRN). In addition, a comparative study of the performance obtained by the different parallel implementations on GPU versus a sequential application on CPU is carried out. In our tests, a multifold speedup was obtained for our optimized parallel implementation of the method on medium class GPU over an equivalent sequential single-core implementation running on a recent Intel i7 CPU. This work can provide useful guidance to researchers in biology, medicine, or bioinformatics in how to take advantage of the parallelization on massively parallel devices and GPUs to apply novel metaheuristic algorithms powered by nature for real-world applications (like the method to solve the temporal dynamics of GRNs).}, } @article {pmid29662249, year = {2018}, author = {Ryan, MR and Crews, TE and Culman, SW and DeHaan, LR and Hayes, RC and Jungers, JM and Bakker, MG}, title = {Managing for Multifunctionality in Perennial Grain Crops.}, journal = {Bioscience}, volume = {68}, number = {4}, pages = {294-304}, pmid = {29662249}, issn = {0006-3568}, abstract = {Plant breeders are increasing yields and improving agronomic traits in several perennial grain crops, the first of which is now being incorporated into commercial food products. Integration strategies and management guidelines are needed to optimize production of these new crops, which differ substantially from both annual grain crops and perennial forages. To offset relatively low grain yields, perennial grain cropping systems should be multifunctional. Growing perennial grains for several years to regenerate soil health before rotating to annual crops and growing perennial grains on sloped land and ecologically sensitive areas to reduce soil erosion and nutrient losses are two strategies that can provide ecosystem services and support multifunctionality. Several perennial cereals can be used to produce both grain and forage, and these dual-purpose crops can be intercropped with legumes for additional benefits. Highly diverse perennial grain polycultures can further enhance ecosystem services, but increased management complexity might limit their adoption.}, } @article {pmid29662248, year = {2018}, author = {Harvey, JA and van den Berg, D and Ellers, J and Kampen, R and Crowther, TW and Roessingh, P and Verheggen, B and Nuijten, RJM and Post, E and Lewandowsky, S and Stirling, I and Balgopal, M and Amstrup, SC and Mann, ME}, title = {Internet Blogs, Polar Bears, and Climate-Change Denial by Proxy.}, journal = {Bioscience}, volume = {68}, number = {4}, pages = {281-287}, pmid = {29662248}, issn = {0006-3568}, abstract = {Increasing surface temperatures, Arctic sea-ice loss, and other evidence of anthropogenic global warming (AGW) are acknowledged by every major scientific organization in the world. However, there is a wide gap between this broad scientific consensus and public opinion. Internet blogs have strongly contributed to this consensus gap by fomenting misunderstandings of AGW causes and consequences. Polar bears (Ursus maritimus) have become a "poster species" for AGW, making them a target of those denying AGW evidence. Here, focusing on Arctic sea ice and polar bears, we show that blogs that deny or downplay AGW disregard the overwhelming scientific evidence of Arctic sea-ice loss and polar bear vulnerability. By denying the impacts of AGW on polar bears, bloggers aim to cast doubt on other established ecological consequences of AGW, aggravating the consensus gap. To counter misinformation and reduce this gap, scientists should directly engage the public in the media and blogosphere.}, } @article {pmid29662247, year = {2018}, author = {McLellan, EL and Cassman, KG and Eagle, AJ and Woodbury, PB and Sela, S and Tonitto, C and Marjerison, RD and van Es, HM}, title = {The Nitrogen Balancing Act: Tracking the Environmental Performance of Food Production.}, journal = {Bioscience}, volume = {68}, number = {3}, pages = {194-203}, pmid = {29662247}, issn = {0006-3568}, abstract = {Farmers, food supply-chain entities, and policymakers need a simple but robust indicator to demonstrate progress toward reducing nitrogen pollution associated with food production. We show that nitrogen balance-the difference between nitrogen inputs and nitrogen outputs in an agricultural production system-is a robust measure of nitrogen losses that is simple to calculate, easily understood, and based on readily available farm data. Nitrogen balance provides farmers with a means of demonstrating to an increasingly concerned public that they are succeeding in reducing nitrogen losses while also improving the overall sustainability of their farming operation. Likewise, supply-chain companies and policymakers can use nitrogen balance to track progress toward sustainability goals. We describe the value of nitrogen balance in translating environmental targets into actionable goals for farmers and illustrate the potential roles of science, policy, and agricultural support networks in helping farmers achieve them.}, } @article {pmid29662227, year = {2018}, author = {Clapham, PJ and Ivashchenko, YV}, title = {Whaling catch data are not reliable for analyses of body size shifts.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {756}, doi = {10.1038/s41559-018-0534-2}, pmid = {29662227}, issn = {2397-334X}, } @article {pmid29662226, year = {2018}, author = {Paquette, A and Hector, A and Castagneyrol, B and Vanhellemont, M and Koricheva, J and Scherer-Lorenzen, M and Verheyen, K and , }, title = {A million and more trees for science.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {763-766}, doi = {10.1038/s41559-018-0544-0}, pmid = {29662226}, issn = {2397-334X}, } @article {pmid29662225, year = {2018}, author = {Clements, CF and Blanchard, JL and Nash, KL and Hindell, MA and Ozgul, A}, title = {Reply to 'Whaling catch data are not reliable for analyses of body size shifts'.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {757-758}, doi = {10.1038/s41559-018-0537-z}, pmid = {29662225}, issn = {2397-334X}, } @article {pmid29662224, year = {2018}, author = {Galiana, N and Lurgi, M and Claramunt-López, B and Fortin, MJ and Leroux, S and Cazelles, K and Gravel, D and Montoya, JM}, title = {The spatial scaling of species interaction networks.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {782-790}, doi = {10.1038/s41559-018-0517-3}, pmid = {29662224}, issn = {2397-334X}, abstract = {Species-area relationships (SARs) are pivotal to understand the distribution of biodiversity across spatial scales. We know little, however, about how the network of biotic interactions in which biodiversity is embedded changes with spatial extent. Here we develop a new theoretical framework that enables us to explore how different assembly mechanisms and theoretical models affect multiple properties of ecological networks across space. We present a number of testable predictions on network-area relationships (NARs) for multi-trophic communities. Network structure changes as area increases because of the existence of different SARs across trophic levels, the preferential selection of generalist species at small spatial extents and the effect of dispersal limitation promoting beta-diversity. Developing an understanding of NARs will complement the growing body of knowledge on SARs with potential applications in conservation ecology. Specifically, combined with further empirical evidence, NARs can generate predictions of potential effects on ecological communities of habitat loss and fragmentation in a changing world.}, } @article {pmid29662223, year = {2018}, author = {Ratzke, C and Denk, J and Gore, J}, title = {Ecological suicide in microbes.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {867-872}, pmid = {29662223}, issn = {2397-334X}, support = {R01 GM102311/GM/NIGMS NIH HHS/United States ; }, abstract = {The growth and survival of organisms often depend on interactions between them. In many cases, these interactions are positive and caused by a cooperative modification of the environment. Examples are the cooperative breakdown of complex nutrients in microbes or the construction of elaborate architectures in social insects, in which the individual profits from the collective actions of her peers. However, organisms can similarly display negative interactions by changing the environment in ways that are detrimental for them, for example by resource depletion or the production of toxic byproducts. Here we find an extreme type of negative interactions, in which Paenibacillus sp. bacteria modify the environmental pH to such a degree that it leads to a rapid extinction of the whole population, a phenomenon that we call ecological suicide. Modification of the pH is more pronounced at higher population densities, and thus ecological suicide is more likely to occur with increasing bacterial density. Correspondingly, promoting bacterial growth can drive populations extinct whereas inhibiting bacterial growth by the addition of harmful substances-such as antibiotics-can rescue them. Moreover, ecological suicide can cause oscillatory dynamics, even in single-species populations. We found ecological suicide in a wide variety of microbes, suggesting that it could have an important role in microbial ecology and evolution.}, } @article {pmid29662222, year = {2018}, author = {Louca, S and Polz, MF and Mazel, F and Albright, MBN and Huber, JA and O'Connor, MI and Ackermann, M and Hahn, AS and Srivastava, DS and Crowe, SA and Doebeli, M and Parfrey, LW}, title = {Function and functional redundancy in microbial systems.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {936-943}, doi = {10.1038/s41559-018-0519-1}, pmid = {29662222}, issn = {2397-334X}, abstract = {Microbial communities often exhibit incredible taxonomic diversity, raising questions regarding the mechanisms enabling species coexistence and the role of this diversity in community functioning. On the one hand, many coexisting but taxonomically distinct microorganisms can encode the same energy-yielding metabolic functions, and this functional redundancy contrasts with the expectation that species should occupy distinct metabolic niches. On the other hand, the identity of taxa encoding each function can vary substantially across space or time with little effect on the function, and this taxonomic variability is frequently thought to result from ecological drift between equivalent organisms. Here, we synthesize the powerful paradigm emerging from these two patterns, connecting the roles of function, functional redundancy and taxonomy in microbial systems. We conclude that both patterns are unlikely to be the result of ecological drift, but are inevitable emergent properties of open microbial systems resulting mainly from biotic interactions and environmental and spatial processes.}, } @article {pmid29662221, year = {2018}, author = {Wood, B}, title = {Colin Groves (1942-2017).}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {922}, doi = {10.1038/s41559-018-0554-y}, pmid = {29662221}, issn = {2397-334X}, } @article {pmid29662211, year = {2018}, author = {Hicks, J and Vasko, P and Goicoechea, JM and Aldridge, S}, title = {Synthesis, structure and reaction chemistry of a nucleophilic aluminyl anion.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {92-95}, doi = {10.1038/s41586-018-0037-y}, pmid = {29662211}, issn = {1476-4687}, abstract = {The reactivity of aluminium compounds is dominated by their electron deficiency and consequent electrophilicity; these compounds are archetypal Lewis acids (electron-pair acceptors). The main industrial roles of aluminium, and classical methods of synthesizing aluminium-element bonds (for example, hydroalumination and metathesis), draw on the electron deficiency of species of the type AlR3 and AlCl31,2. Whereas aluminates, [AlR4]-, are well known, the idea of reversing polarity and using an aluminium reagent as the nucleophilic partner in bond-forming substitution reactions is unprecedented, owing to the fact that low-valent aluminium anions analogous to nitrogen-, carbon- and boron-centred reagents of the types [NX2]-, [CX3]- and [BX2]- are unknown3-5. Aluminium compounds in the +1 oxidation state are known, but are thermodynamically unstable with respect to disproportionation. Compounds of this type are typically oligomeric6-8, although monomeric systems that possess a metal-centred lone pair, such as Al(Nacnac)Dipp (where (Nacnac)Dipp = (NDippCR)2CH and R = t Bu, Me; Dipp = 2,6- i Pr2C6H3), have also been reported9,10. Coordination of these species, and also of (η5-C5Me5)Al, to a range of Lewis acids has been observed11-13, but their primary mode of reactivity involves facile oxidative addition to generate Al(III) species6-8,14-16. Here we report the synthesis, structure and reaction chemistry of an anionic aluminium(I) nucleophile, the dimethylxanthene-stabilized potassium aluminyl [K{Al(NON)}]2 (NON = 4,5-bis(2,6-diisopropylanilido)-2,7-di-tert-butyl-9,9-dimethylxanthene). This species displays unprecedented reactivity in the formation of aluminium-element covalent bonds and in the C-H oxidative addition of benzene, suggesting that it could find further use in both metal-carbon and metal-metal bond-forming reactions.}, } @article {pmid29662168, year = {2018}, author = {Hysi, PG and Valdes, AM and Liu, F and Furlotte, NA and Evans, DM and Bataille, V and Visconti, A and Hemani, G and McMahon, G and Ring, SM and Smith, GD and Duffy, DL and Zhu, G and Gordon, SD and Medland, SE and Lin, BD and Willemsen, G and Jan Hottenga, J and Vuckovic, D and Girotto, G and Gandin, I and Sala, C and Concas, MP and Brumat, M and Gasparini, P and Toniolo, D and Cocca, M and Robino, A and Yazar, S and Hewitt, AW and Chen, Y and Zeng, C and Uitterlinden, AG and Ikram, MA and Hamer, MA and van Duijn, CM and Nijsten, T and Mackey, DA and Falchi, M and Boomsma, DI and Martin, NG and Hinds, DA and Kayser, M and Spector, TD and , and , }, title = {Genome-wide association meta-analysis of individuals of European ancestry identifies new loci explaining a substantial fraction of hair color variation and heritability.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {652-656}, pmid = {29662168}, issn = {1546-1718}, support = {RC2 MH089951/MH/NIMH NIH HHS/United States ; 105022//Wellcome Trust/United Kingdom ; 072856//Wellcome Trust/United Kingdom ; R01 AA007535/AA/NIAAA NIH HHS/United States ; R01 AA014041/AA/NIAAA NIH HHS/United States ; R01 MH081802/MH/NIMH NIH HHS/United States ; R01 MH066206/MH/NIMH NIH HHS/United States ; RC2 MH089995/MH/NIMH NIH HHS/United States ; 202786//Wellcome Trust/United Kingdom ; R01 HD042157/HD/NICHD NIH HHS/United States ; R01 AA013326/AA/NIAAA NIH HHS/United States ; R01 AA013321/AA/NIAAA NIH HHS/United States ; 230374//European Research Council/International ; 079771//Wellcome Trust/United Kingdom ; U24 MH068457/MH/NIMH NIH HHS/United States ; //Wellcome Trust/United Kingdom ; 099194//Wellcome Trust/United Kingdom ; R01 AA013320/AA/NIAAA NIH HHS/United States ; 091855//Wellcome Trust/United Kingdom ; }, abstract = {Hair color is one of the most recognizable visual traits in European populations and is under strong genetic control. Here we report the results of a genome-wide association study meta-analysis of almost 300,000 participants of European descent. We identified 123 autosomal and one X-chromosome loci significantly associated with hair color; all but 13 are novel. Collectively, single-nucleotide polymorphisms associated with hair color within these loci explain 34.6% of red hair, 24.8% of blond hair, and 26.1% of black hair heritability in the study populations. These results confirm the polygenic nature of complex phenotypes and improve our understanding of melanin pigment metabolism in humans.}, } @article {pmid29662167, year = {2018}, author = {Wedge, DC and Gundem, G and Mitchell, T and Woodcock, DJ and Martincorena, I and Ghori, M and Zamora, J and Butler, A and Whitaker, H and Kote-Jarai, Z and Alexandrov, LB and Van Loo, P and Massie, CE and Dentro, S and Warren, AY and Verrill, C and Berney, DM and Dennis, N and Merson, S and Hawkins, S and Howat, W and Lu, YJ and Lambert, A and Kay, J and Kremeyer, B and Karaszi, K and Luxton, H and Camacho, N and Marsden, L and Edwards, S and Matthews, L and Bo, V and Leongamornlert, D and McLaren, S and Ng, A and Yu, Y and Zhang, H and Dadaev, T and Thomas, S and Easton, DF and Ahmed, M and Bancroft, E and Fisher, C and Livni, N and Nicol, D and Tavaré, S and Gill, P and Greenman, C and Khoo, V and Van As, N and Kumar, P and Ogden, C and Cahill, D and Thompson, A and Mayer, E and Rowe, E and Dudderidge, T and Gnanapragasam, V and Shah, NC and Raine, K and Jones, D and Menzies, A and Stebbings, L and Teague, J and Hazell, S and Corbishley, C and , and de Bono, J and Attard, G and Isaacs, W and Visakorpi, T and Fraser, M and Boutros, PC and Bristow, RG and Workman, P and Sander, C and , and Hamdy, FC and Futreal, A and McDermott, U and Al-Lazikani, B and Lynch, AG and Bova, GS and Foster, CS and Brewer, DS and Neal, DE and Cooper, CS and Eeles, RA}, title = {Sequencing of prostate cancers identifies new cancer genes, routes of progression and drug targets.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {682-692}, doi = {10.1038/s41588-018-0086-z}, pmid = {29662167}, issn = {1546-1718}, support = {14835//Cancer Research UK/United Kingdom ; }, abstract = {Prostate cancer represents a substantial clinical challenge because it is difficult to predict outcome and advanced disease is often fatal. We sequenced the whole genomes of 112 primary and metastatic prostate cancer samples. From joint analysis of these cancers with those from previous studies (930 cancers in total), we found evidence for 22 previously unidentified putative driver genes harboring coding mutations, as well as evidence for NEAT1 and FOXA1 acting as drivers through noncoding mutations. Through the temporal dissection of aberrations, we identified driver mutations specifically associated with steps in the progression of prostate cancer, establishing, for example, loss of CHD1 and BRCA2 as early events in cancer development of ETS fusion-negative cancers. Computational chemogenomic (canSAR) analysis of prostate cancer mutations identified 11 targets of approved drugs, 7 targets of investigational drugs, and 62 targets of compounds that may be active and should be considered candidates for future clinical trials.}, } @article {pmid29662166, year = {2018}, author = {Zeng, J and de Vlaming, R and Wu, Y and Robinson, MR and Lloyd-Jones, LR and Yengo, L and Yap, CX and Xue, A and Sidorenko, J and McRae, AF and Powell, JE and Montgomery, GW and Metspalu, A and Esko, T and Gibson, G and Wray, NR and Visscher, PM and Yang, J}, title = {Signatures of negative selection in the genetic architecture of human complex traits.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {746-753}, doi = {10.1038/s41588-018-0101-4}, pmid = {29662166}, issn = {1546-1718}, abstract = {We develop a Bayesian mixed linear model that simultaneously estimates single-nucleotide polymorphism (SNP)-based heritability, polygenicity (proportion of SNPs with nonzero effects), and the relationship between SNP effect size and minor allele frequency for complex traits in conventionally unrelated individuals using genome-wide SNP data. We apply the method to 28 complex traits in the UK Biobank data (N = 126,752) and show that on average, 6% of SNPs have nonzero effects, which in total explain 22% of phenotypic variance. We detect significant (P < 0.05/28) signatures of natural selection in the genetic architecture of 23 traits, including reproductive, cardiovascular, and anthropometric traits, as well as educational attainment. The significant estimates of the relationship between effect size and minor allele frequency in complex traits are consistent with a model of negative (or purifying) selection, as confirmed by forward simulation. We conclude that negative selection acts pervasively on the genetic variants associated with human complex traits.}, } @article {pmid29662165, year = {2018}, author = {Suzuki, HI and Spengler, RM and Grigelioniene, G and Kobayashi, T and Sharp, PA}, title = {Deconvolution of seed and RNA-binding protein crosstalk in RNAi-based functional genomics.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {657-661}, pmid = {29662165}, issn = {1546-1718}, support = {P30 CA014051/CA/NCI NIH HHS/United States ; R01 AR056645/AR/NIAMS NIH HHS/United States ; R01 CA133404/CA/NCI NIH HHS/United States ; R01 GM034277/GM/NIGMS NIH HHS/United States ; }, abstract = {RNA interference (RNAi) is a major, powerful platform for gene perturbations, but is restricted by off-target mechanisms. Communication between RNAs, small RNAs, and RNA-binding proteins (RBPs) is a pervasive feature of cellular RNA networks. We present a crosstalk scenario, designated as crosstalk with endogenous RBPs' (ceRBP), in which small interfering RNAs or microRNAs with seed sequences that overlap RBP motifs have extended biological effects by perturbing endogenous RBP activity. Systematic analysis of small interfering RNA (siRNA) off-target data and genome-wide RNAi cancer lethality screens using 501 human cancer cell lines, a cancer dependency map, identified that seed-to-RBP crosstalk is widespread, contributes to off-target activity, and affects RNAi performance. Specifically, deconvolution of the interactions between gene knockdown and seed-mediated silencing effects in the cancer dependency map showed widespread contributions of seed-to-RBP crosstalk to growth-phenotype modulation. These findings suggest a novel aspect of microRNA biology and offer a basis for improvement of RNAi agents and RNAi-based functional genomics.}, } @article {pmid29662164, year = {2018}, author = {Harley, JB and Chen, X and Pujato, M and Miller, D and Maddox, A and Forney, C and Magnusen, AF and Lynch, A and Chetal, K and Yukawa, M and Barski, A and Salomonis, N and Kaufman, KM and Kottyan, LC and Weirauch, MT}, title = {Transcription factors operate across disease loci, with EBNA2 implicated in autoimmunity.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {699-707}, pmid = {29662164}, issn = {1546-1718}, support = {U01 AI130830/AI/NIAID NIH HHS/United States ; R01 NS099068/NS/NINDS NIH HHS/United States ; KL2 TR001426/TR/NCATS NIH HHS/United States ; R01 AI031584/AI/NIAID NIH HHS/United States ; R21 HG008186/HG/NHGRI NIH HHS/United States ; R01 DK107502/DK/NIDDK NIH HHS/United States ; P30 DK078392/DK/NIDDK NIH HHS/United States ; R24 HL105333/HL/NHLBI NIH HHS/United States ; R01 AI024717/AI/NIAID NIH HHS/United States ; U01 HG008666/HG/NHGRI NIH HHS/United States ; P30 AR070549/AR/NIAMS NIH HHS/United States ; DP2 GM119134/GM/NIGMS NIH HHS/United States ; I01 BX001834/BX/BLRD VA/United States ; }, abstract = {Explaining the genetics of many diseases is challenging because most associations localize to incompletely characterized regulatory regions. Using new computational methods, we show that transcription factors (TFs) occupy multiple loci associated with individual complex genetic disorders. Application to 213 phenotypes and 1,544 TF binding datasets identified 2,264 relationships between hundreds of TFs and 94 phenotypes, including androgen receptor in prostate cancer and GATA3 in breast cancer. Strikingly, nearly half of systemic lupus erythematosus risk loci are occupied by the Epstein-Barr virus EBNA2 protein and many coclustering human TFs, showing gene-environment interaction. Similar EBNA2-anchored associations exist in multiple sclerosis, rheumatoid arthritis, inflammatory bowel disease, type 1 diabetes, juvenile idiopathic arthritis and celiac disease. Instances of allele-dependent DNA binding and downstream effects on gene expression at plausibly causal variants support genetic mechanisms dependent on EBNA2. Our results nominate mechanisms that operate across risk loci within disease phenotypes, suggesting new models for disease origins.}, } @article {pmid29662163, year = {2018}, author = {Bianco, S and Lupiáñez, DG and Chiariello, AM and Annunziatella, C and Kraft, K and Schöpflin, R and Wittler, L and Andrey, G and Vingron, M and Pombo, A and Mundlos, S and Nicodemi, M}, title = {Polymer physics predicts the effects of structural variants on chromatin architecture.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {662-667}, doi = {10.1038/s41588-018-0098-8}, pmid = {29662163}, issn = {1546-1718}, abstract = {Structural variants (SVs) can result in changes in gene expression due to abnormal chromatin folding and cause disease. However, the prediction of such effects remains a challenge. Here we present a polymer-physics-based approach (PRISMR) to model 3D chromatin folding and to predict enhancer-promoter contacts. PRISMR predicts higher-order chromatin structure from genome-wide chromosome conformation capture (Hi-C) data. Using the EPHA4 locus as a model, the effects of pathogenic SVs are predicted in silico and compared to Hi-C data generated from mouse limb buds and patient-derived fibroblasts. PRISMR deconvolves the folding complexity of the EPHA4 locus and identifies SV-induced ectopic contacts and alterations of 3D genome organization in homozygous or heterozygous states. We show that SVs can reconfigure topologically associating domains, thereby producing extensive rewiring of regulatory interactions and causing disease by gene misexpression. PRISMR can be used to predict interactions in silico, thereby providing a tool for analyzing the disease-causing potential of SVs.}, } @article {pmid29662138, year = {2018}, author = {Taddeo, M and Floridi, L}, title = {Regulate artificial intelligence to avert cyber arms race.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {296-298}, doi = {10.1038/d41586-018-04602-6}, pmid = {29662138}, issn = {1476-4687}, } @article {pmid29662135, year = {2018}, author = {Levesque, S and Moineau, S}, title = {A stockpile of antiviral defences.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {318-319}, doi = {10.1038/d41586-018-04367-y}, pmid = {29662135}, issn = {1476-4687}, mesh = {*Antiviral Agents ; Microbiology ; *Pandemics ; Virology ; }, } @article {pmid29662134, year = {2018}, author = {Morris, MR}, title = {Bounteous black holes at the Galactic Centre.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {319-320}, doi = {10.1038/d41586-018-04341-8}, pmid = {29662134}, issn = {1476-4687}, } @article {pmid29662133, year = {2018}, author = {Kokko, H}, title = {When sex differences lead to extinction.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {315-316}, doi = {10.1038/d41586-018-04059-7}, pmid = {29662133}, issn = {1476-4687}, mesh = {Biological Evolution ; Female ; Fossils ; Humans ; Male ; *Paleontology ; *Sex Characteristics ; }, } @article {pmid29662132, year = {2018}, author = {Nott, A and Glass, CK}, title = {Immune memory in the brain.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {312-313}, doi = {10.1038/d41586-018-03800-6}, pmid = {29662132}, issn = {1476-4687}, mesh = {Brain ; *Immunologic Memory ; *Memory ; Memory Disorders ; }, } @article {pmid29662129, year = {2018}, author = {Ercoli, G and Fernandes, VE and Chung, WY and Wanford, JJ and Thomson, S and Bayliss, CD and Straatman, K and Crocker, PR and Dennison, A and Martinez-Pomares, L and Andrew, PW and Moxon, ER and Oggioni, MR}, title = {Intracellular replication of Streptococcus pneumoniae inside splenic macrophages serves as a reservoir for septicaemia.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {600-610}, pmid = {29662129}, issn = {2058-5276}, support = {MR/M003078/1//Medical Research Council/United Kingdom ; }, abstract = {Bacterial septicaemia is a major cause of mortality, but its pathogenesis remains poorly understood. In experimental pneumococcal murine intravenous infection, an initial reduction of bacteria in the blood is followed hours later by a fatal septicaemia. These events represent a population bottleneck driven by efficient clearance of pneumococci by splenic macrophages and neutrophils, but as we show in this study, accompanied by occasional intracellular replication of bacteria that are taken up by a subset of CD169+ splenic macrophages. In this model, proliferation of these sequestered bacteria provides a reservoir for dissemination of pneumococci into the bloodstream, as demonstrated by its prevention using an anti-CD169 monoclonal antibody treatment. Intracellular replication of pneumococci within CD169+ splenic macrophages was also observed in an ex vivo porcine spleen, where the microanatomy is comparable with humans. We also showed that macrolides, which effectively penetrate macrophages, prevented septicaemia, whereas beta-lactams, with inefficient intracellular penetration, failed to prevent dissemination to the blood. Our findings define a shift in our understanding of the pneumococcus from an exclusively extracellular pathogen to one with an intracellular phase. These findings open the door to the development of treatments that target this early, previously unrecognized intracellular phase of bacterial sepsis.}, } @article {pmid29662128, year = {2018}, author = {Liu, Y and Liu, FJ and Guan, ZC and Dong, FT and Cheng, JH and Gao, YP and Li, D and Yan, J and Liu, CH and Han, DP and Ma, CM and Feng, JN and Shen, BF and Yang, G}, title = {The extracellular domain of Staphylococcus aureus LtaS binds insulin and induces insulin resistance during infection.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {622-631}, doi = {10.1038/s41564-018-0146-2}, pmid = {29662128}, issn = {2058-5276}, abstract = {Insulin resistance is a risk factor for obesity and diabetes and predisposes individuals to Staphylococcus aureus colonization; however, the contribution of S. aureus to insulin resistance remains unclear. Here, we show that S. aureus infection causes impaired glucose tolerance via secretion of an insulin-binding protein extracellular domain of LtaS, eLtaS, which blocks insulin-mediated glucose uptake. Notably, eLtaS transgenic mice (eLtaS trans) exhibited a metabolic syndrome similar to that observed in patients, including increased food and water consumption, impaired glucose tolerance and decreased hepatic glycogen synthesis. Furthermore, transgenic mice showed significant metabolic differences compared to their wild-type counterparts, particularly for the early insulin resistance marker α-hydroxybutyrate. We subsequently developed a full human monoclonal antibody against eLtaS that blocked the interaction between eLtaS and insulin, which effectively restored glucose tolerance in eLtaS trans and S. aureus-challenged mice. Thus, our results reveal a mechanism for S. aureus-induced insulin resistance.}, } @article {pmid29662123, year = {2018}, author = {Wrighton, K}, title = {Nanowires under the microscope.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {330}, doi = {10.1038/s41579-018-0012-5}, pmid = {29662123}, issn = {1740-1534}, } @article {pmid29661791, year = {2018}, author = {Alspach, E and Lussier, DM and Schreiber, RD}, title = {Interferon γ and Its Important Roles in Promoting and Inhibiting Spontaneous and Therapeutic Cancer Immunity.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {}, number = {}, pages = {}, doi = {10.1101/cshperspect.a028480}, pmid = {29661791}, issn = {1943-0264}, abstract = {Originally identified in studies of cellular resistance to viral infection, interferon (IFN)-γ is now known to represent a distinct member of the IFN family and plays critical roles not only in orchestrating both innate and adaptive immune responses against viruses, bacteria, and tumors, but also in promoting pathologic inflammatory processes. IFN-γ production is largely restricted to T lymphocytes and natural killer (NK) cells and can ultimately lead to the generation of a polarized immune response composed of T helper (Th)1 CD4+ T cells and CD8+ cytolytic T cells. In contrast, the temporally distinct elaboration of IFN-γ in progressively growing tumors also promotes a state of adaptive resistance caused by the up-regulation of inhibitory molecules, such as programmed-death ligand 1 (PD-L1) on tumor cell targets, and additional host cells within the tumor microenvironment. This review focuses on the diverse positive and negative roles of IFN-γ in immune cell activation and differentiation leading to protective immune responses, as well as the paradoxical effects of IFN-γ within the tumor microenvironment that determine the ultimate fate of that tumor in a cancer-bearing individual.}, } @article {pmid29661790, year = {2018}, author = {Rodnina, MV}, title = {Translation in Prokaryotes.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a032664}, pmid = {29661790}, issn = {1943-0264}, abstract = {This review summarizes our current understanding of translation in prokaryotes, focusing on the mechanistic and structural aspects of each phase of translation: initiation, elongation, termination, and ribosome recycling. The assembly of the initiation complex provides multiple checkpoints for messenger RNA (mRNA) and start-site selection. Correct codon-anticodon interaction during the decoding phase of elongation results in major conformational changes of the small ribosomal subunit and shapes the reaction pathway of guanosine triphosphate (GTP) hydrolysis. The ribosome orchestrates proton transfer during peptide bond formation, but requires the help of elongation factor P (EF-P) when two or more consecutive Pro residues are to be incorporated. Understanding the choreography of transfer RNA (tRNA) and mRNA movements during translocation helps to place the available structures of translocation intermediates onto the time axis of the reaction pathway. The nascent protein begins to fold cotranslationally, in the constrained space of the polypeptide exit tunnel of the ribosome. When a stop codon is reached at the end of the coding sequence, the ribosome, assisted by termination factors, hydrolyzes the ester bond of the peptidyl-tRNA, thereby releasing the nascent protein. Following termination, the ribosome is dissociated into subunits and recycled into another round of initiation. At each step of translation, the ribosome undergoes dynamic fluctuations between different conformation states. The aim of this article is to show the link between ribosome structure, dynamics, and function.}, } @article {pmid29661654, year = {2018}, author = {Keesing, F and Ostfeld, RS}, title = {The Tick Project: Testing Environmental Methods of Preventing Tick-borne Diseases: (Trends in Parasitology Vol 34, 447-450 2018).}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {541}, doi = {10.1016/j.pt.2018.03.005}, pmid = {29661654}, issn = {1471-5007}, } @article {pmid29661251, year = {2018}, author = {Alemu, M and Zigta, E and Derbie, A}, title = {Under diagnosis of intestinal schistosomiasis in a referral hospital, North Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {245}, pmid = {29661251}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Animals ; Child ; Child, Preschool ; Clinical Laboratory Techniques/methods/*standards ; Cross-Sectional Studies ; Ethiopia ; Feces/*parasitology ; Female ; Formaldehyde ; Hospitals/statistics & numerical data ; Humans ; Male ; Microscopy/standards ; Predictive Value of Tests ; Referral and Consultation ; *Schistosoma mansoni ; Schistosomiasis mansoni/*diagnosis ; Sensitivity and Specificity ; Young Adult ; }, abstract = {OBJECTIVE: The present cross-sectional study was aimed at determining the magnitude of under diagnosis of intestinal schistosomiasis among patients requested for routine ova/parasite examination at Ayder referral hospital.

RESULTS: A total of 280 stool samples were collected and only 5% of the patients were positive for ova of Schistosoma mansoni in the routine direct wet mount microscopy. On the other hand, 12.5% of the patients were positive for ova Schistosoma mansoni when the stool samples were processed by either Kato Kat or formol ether concentration techniques. Moderate test agreement (κ = 0.48) was recorded for wet mount. Formol-ether concentration (κ = 0.89) and Kato-Katz (κ = 0.92) showed excellent agreements with the 'Gold' standard. Direct wet mount technique exhibited the poorest sensitivity (35%) of detection of ova of Schistosoma mansoni. Hence, the Kato-Katz technique should be implemented in parallel with the direct wet mount microscopy for Schistosoma mansoni presumptive patients.}, } @article {pmid29661230, year = {2018}, author = {Gomez-Silvan, C and Leung, MHY and Grue, KA and Kaur, R and Tong, X and Lee, PKH and Andersen, GL}, title = {A comparison of methods used to unveil the genetic and metabolic pool in the built environment.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {71}, pmid = {29661230}, issn = {2049-2618}, support = {G-2015-13977//Alfred P. Sloan Foundation/International ; 11276116//Research Grants Council, University Grants Committee/International ; }, mesh = {*Built Environment ; *Environmental Microbiology ; Humans ; *Metabolomics/methods ; *Metagenomics/methods ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: A majority of indoor residential microbes originate from humans, pets, and outdoor air and are not adapted to the built environment (BE). Consequently, a large portion of the microbes identified by DNA-based methods are either dead or metabolically inactive. Although many exceptions have been noted, the ribosomal RNA fraction of the sample is more likely to represent either viable or metabolically active cells. We examined methodological variations in sample processing using a defined, mock BE microbial community to better understand the scope of technique-based vs. biological-based differences in both ribosomal transcript (rRNA) and gene (DNA) sequence community analysis. Based on in vitro tests, a protocol was adopted for the analysis of the genetic and metabolic pool (DNA vs. rRNA) of air and surface microbiomes within a residential setting.

RESULTS: We observed differences in DNA/RNA co-extraction efficiency for individual microbes, but overall, a greater recovery of rRNA using FastPrep (> 50%). Samples stored with various preservation methods at - 80°C experienced a rapid decline in nucleic acid recovery starting within the first week, although post-extraction rRNA had no significant degradation when treated with RNAStable. We recommend that co-extraction samples be processed as quickly as possible after collection. The in vivo analysis revealed significant differences in the two components (genetic and metabolic pool) in terms of taxonomy, community structure, and microbial association networks. Rare taxa present in the genetic pool showed higher metabolic potential (RNA:DNA ratio), whereas commonly detected taxa of outdoor origins based on DNA sequencing, especially taxa of the Sphingomonadales order, were present in lower relative abundances in the viable community.

CONCLUSIONS: Although methodological variations in sample preparations are high, large differences between the DNA and RNA fractions of the total microbial community demonstrate that direct examination of rRNA isolated from a residential BE microbiome has the potential to identify the more likely viable or active portion of the microbial community. In an environment that has primarily dead and metabolically inactive cells, we suggest that the rRNA fraction of BE samples is capable of providing a more ecologically relevant insight into the factors that drive indoor microbial community dynamics.}, } @article {pmid29661224, year = {2018}, author = {Paul, MS and Singh, A and Dutta, D and Mutsuddi, M and Mukherjee, A}, title = {Notch signals modulate lgl mediated tumorigenesis by the activation of JNK signaling.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {247}, pmid = {29661224}, issn = {1756-0500}, support = {BT/PR14082/BRB/10/806/2010//Department of Biotechnology , Ministry of Science and Technology/ ; BT/PR14080/BRB/10/805/2010//Department of Biotechnology , Ministry of Science and Technology/ ; }, mesh = {Animals ; Carcinogenesis/*metabolism ; Cell Death/*physiology ; Drosophila/*metabolism ; Drosophila Proteins/*metabolism ; MAP Kinase Signaling System/*physiology ; Models, Animal ; Receptors, Notch/*metabolism ; Tumor Suppressor Proteins/*metabolism ; }, abstract = {OBJECTIVES: Oncogenic potential of Notch signaling and its cooperation with other factors to affect proliferation are widely established. Notch exhibits a cooperative effect with loss of a cell polarity gene, scribble to induce neoplastic overgrowth. Oncogenic Ras also show cooperative effect with loss of cell polarity genes such as scribble (scrib), lethal giant larvae (lgl) and discs large to induce neoplastic overgrowth and invasion. Our study aims at assessing the cooperation of activated Notch with loss of function of lgl in tumor overgrowth, and the mode of JNK signaling activation in this context.

RESULTS: In the present study, we use Drosophila as an in vivo model to show the synergy between activated Notch (N act) and loss of function of lgl (lgl-IR) in tumor progression. Coexpression of N act and lgl-IR results in massive tumor overgrowth and displays hallmarks of cancer, such as MMP1 upregulation and loss of epithelial integrity. We further show activation of JNK signaling and upregulation of its receptor, Grindelwald in N act /lgl-IR tumor. In contrast to previously described Notch act /scrib-/- tumor, our experiments in N act /lgl-IR tumor showed the presence of dying cells along with tumorous overgrowth.}, } @article {pmid29661206, year = {2018}, author = {Vadloori, B and Sharath, AK and Prabhu, NP and Maurya, R}, title = {Homology modelling, molecular docking, and molecular dynamics simulations reveal the inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase enzyme by Withaferin-A.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {246}, pmid = {29661206}, issn = {1756-0500}, mesh = {Enzyme Inhibitors/*pharmacology ; Folic Acid/*analogs & derivatives/pharmacology ; Humans ; Leishmania donovani/*enzymology ; Methotrexate/*pharmacology ; *Molecular Docking Simulation ; *Molecular Dynamics Simulation ; Multienzyme Complexes/*drug effects ; Plant Extracts/*pharmacology ; Tetrahydrofolate Dehydrogenase/*drug effects ; Thymidylate Synthase/*drug effects ; *Withania ; Withanolides/*pharmacology ; }, abstract = {OBJECTIVE: Present in silico study was carried out to explore the mode of inhibition of Leishmania donovani dihydrofolate reductase-thymidylate synthase (Ld DHFR-TS) enzyme by Withaferin-A, a withanolide isolated from Withania somnifera. Withaferin-A (WA) is known for its profound multifaceted properties, but its antileishmanial activity is not well understood. The parasite's DHFR-TS enzyme is diverse from its mammalian host and could be a potential drug target in parasites.

RESULTS: A 3D model of Ld DHFR-TS enzyme was built and verified using Ramachandran plot and SAVES tools. The protein was docked with WA-the ligand, methotrexate (MTX)-competitive inhibitor of DHFR, and dihydrofolic acid (DHFA)-substrate for DHFR-TS. Molecular docking studies reveal that WA competes for active sites of both Hu DHFR and TS enzymes whereas it binds to a site other than active site in Ld DHFR-TS. Moreover, Lys 173 residue of DHFR-TS forms a H-bond with WA and has higher binding affinity to Ld DHFR-TS than Hu DHFR and Hu TS. The MD simulations confirmed the H-bonding interactions were stable. The binding energies of WA with Ld DHFR-TS were calculated using MM-PBSA. Homology modelling, molecular docking and MD simulations of Ld DHFR-TS revealed that WA could be a potential anti-leishmanial drug.}, } @article {pmid29661190, year = {2018}, author = {Pilkington, SM and Crowhurst, R and Hilario, E and Nardozza, S and Fraser, L and Peng, Y and Gunaseelan, K and Simpson, R and Tahir, J and Deroles, SC and Templeton, K and Luo, Z and Davy, M and Cheng, C and McNeilage, M and Scaglione, D and Liu, Y and Zhang, Q and Datson, P and De Silva, N and Gardiner, SE and Bassett, H and Chagné, D and McCallum, J and Dzierzon, H and Deng, C and Wang, YY and Barron, L and Manako, K and Bowen, J and Foster, TM and Erridge, ZA and Tiffin, H and Waite, CN and Davies, KM and Grierson, EP and Laing, WA and Kirk, R and Chen, X and Wood, M and Montefiori, M and Brummell, DA and Schwinn, KE and Catanach, A and Fullerton, C and Li, D and Meiyalaghan, S and Nieuwenhuizen, N and Read, N and Prakash, R and Hunter, D and Zhang, H and McKenzie, M and Knäbel, M and Harris, A and Allan, AC and Gleave, A and Chen, A and Janssen, BJ and Plunkett, B and Ampomah-Dwamena, C and Voogd, C and Leif, D and Lafferty, D and Souleyre, EJF and Varkonyi-Gasic, E and Gambi, F and Hanley, J and Yao, JL and Cheung, J and David, KM and Warren, B and Marsh, K and Snowden, KC and Lin-Wang, K and Brian, L and Martinez-Sanchez, M and Wang, M and Ileperuma, N and Macnee, N and Campin, R and McAtee, P and Drummond, RSM and Espley, RV and Ireland, HS and Wu, R and Atkinson, RG and Karunairetnam, S and Bulley, S and Chunkath, S and Hanley, Z and Storey, R and Thrimawithana, AH and Thomson, S and David, C and Testolin, R and Huang, H and Hellens, RP and Schaffer, RJ}, title = {A manually annotated Actinidia chinensis var. chinensis (kiwifruit) genome highlights the challenges associated with draft genomes and gene prediction in plants.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {257}, pmid = {29661190}, issn = {1471-2164}, support = {C#27353//Ministry of Business, Innovation and Employment/ ; KRIP Genome//Kiwifruit Royalty Investment Program by the New Zealand Institute for Plant and Food Research/ ; }, mesh = {Actinidia/*genetics ; Genes, Plant ; *Genome, Plant ; Genotype ; Molecular Sequence Annotation ; Plant Proteins/genetics ; }, abstract = {BACKGROUND: Most published genome sequences are drafts, and most are dominated by computational gene prediction. Draft genomes typically incorporate considerable sequence data that are not assigned to chromosomes, and predicted genes without quality confidence measures. The current Actinidia chinensis (kiwifruit) 'Hongyang' draft genome has 164 Mb of sequences unassigned to pseudo-chromosomes, and omissions have been identified in the gene models.

RESULTS: A second genome of an A. chinensis (genotype Red5) was fully sequenced. This new sequence resulted in a 554.0 Mb assembly with all but 6 Mb assigned to pseudo-chromosomes. Pseudo-chromosomal comparisons showed a considerable number of translocation events have occurred following a whole genome duplication (WGD) event some consistent with centromeric Robertsonian-like translocations. RNA sequencing data from 12 tissues and ab initio analysis informed a genome-wide manual annotation, using the WebApollo tool. In total, 33,044 gene loci represented by 33,123 isoforms were identified, named and tagged for quality of evidential support. Of these 3114 (9.4%) were identical to a protein within 'Hongyang' The Kiwifruit Information Resource (KIR v2). Some proportion of the differences will be varietal polymorphisms. However, as most computationally predicted Red5 models required manual re-annotation this proportion is expected to be small. The quality of the new gene models was tested by fully sequencing 550 cloned 'Hort16A' cDNAs and comparing with the predicted protein models for Red5 and both the original 'Hongyang' assembly and the revised annotation from KIR v2. Only 48.9% and 63.5% of the cDNAs had a match with 90% identity or better to the original and revised 'Hongyang' annotation, respectively, compared with 90.9% to the Red5 models.

CONCLUSIONS: Our study highlights the need to take a cautious approach to draft genomes and computationally predicted genes. Our use of the manual annotation tool WebApollo facilitated manual checking and correction of gene models enabling improvement of computational prediction. This utility was especially relevant for certain types of gene families such as the EXPANSIN like genes. Finally, this high quality gene set will supply the kiwifruit and general plant community with a new tool for genomics and other comparative analysis.}, } @article {pmid29661185, year = {2018}, author = {Hara, Y and Takeuchi, M and Kageyama, Y and Tatsumi, K and Hibi, M and Kiyonari, H and Kuraku, S}, title = {Madagascar ground gecko genome analysis characterizes asymmetric fates of duplicated genes.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {40}, pmid = {29661185}, issn = {1741-7007}, abstract = {BACKGROUND: Conventionally, comparison among amniotes - birds, mammals, and reptiles - has often been approached through analyses of mammals and, for comparison, birds. However, birds are morphologically and physiologically derived and, moreover, some parts of their genomes are recognized as difficult to sequence and/or assemble and are thus missing in genome assemblies. Therefore, sequencing the genomes of reptiles would aid comparative studies on amniotes by providing more comprehensive coverage to help understand the molecular mechanisms underpinning evolutionary changes.

RESULTS: Herein, we present the whole genome sequences of the Madagascar ground gecko (Paroedura picta), a promising study system especially in developmental biology, and used it to identify changes in gene repertoire across amniotes. The genome-wide analysis of the Madagascar ground gecko allowed us to reconstruct a comprehensive set of gene phylogenies comprising 13,043 ortholog groups from diverse amniotes. Our study revealed 469 genes retained by some reptiles but absent from available genome-wide sequence data of both mammals and birds. Importantly, these genes, herein collectively designated as 'elusive' genes, exhibited high nucleotide substitution rates and uneven intra-genomic distribution. Furthermore, the genomic regions flanking these elusive genes exhibited distinct characteristics that tended to be associated with increased gene density, repeat element density, and GC content.

CONCLUSION: This highly continuous and nearly complete genome assembly of the Madagascar ground gecko will facilitate the use of this species as an experimental animal in diverse fields of biology. Gene repertoire comparisons across amniotes further demonstrated that the fate of a duplicated gene can be affected by the intrinsic properties of its genomic location, which can persist for hundreds of millions of years.}, } @article {pmid29661152, year = {2018}, author = {Ajayi, C and Åberg, E and Askarian, F and Sollid, JUE and Johannessen, M and Hanssen, AM}, title = {Genetic variability in the sdrD gene in Staphylococcus aureus from healthy nasal carriers.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {34}, pmid = {29661152}, issn = {1471-2180}, abstract = {BACKGROUND: Staphylococcus aureus cell wall anchored Serine Aspartate repeat containing protein D (SdrD) is a member of the microbial surface component recognising adhesive matrix molecules (MSCRAMMs). It is involved in the bacterial adhesion and virulence. However the extent of genetic variation in S. aureus sdrD gene within isolates from healthy carriers are not known. The aim of this study was to evaluate allelic variation of the sdrD gene among S. aureus from healthy nasal carriers.

RESULTS: The sdrD A region from 48 S. aureus isolates from healthy carriers were analysed and classified into seven variants. Variations in the sdrD A region were concentrated in the N2 and N3 subdomains. Sequence analysis of the entire sdrD gene of representative isolates revealed variations in the SD repeat and the EF motifs of the B repeat. In silico structural modelling indicates that there are no differences in the SdrD structure of the 7 variants. Variable amino acid residues mapped onto the 3D structure revealed that the variations are surface located, exist within the groove between the N2-N3 subdomains and distributed mainly on the N3 subdomain. Comparison of adhesion to keratinocytes in an in vitro cell adhesion assay, using NCTC 8325-4∆sdrD strains expressing the various sdrD gene variants, indicated a significant difference between only two complements while others showed no major difference in their adhesion.

CONCLUSIONS: This study provides evidence of sequence variations across the different domains of SdrD from S. aureus isolated from healthy nasal carriers. Proper understanding of these variations is necessary in the study of S. aureus pathogenesis.}, } @article {pmid29661149, year = {2018}, author = {Pena Cortes, LC and LeVeque, RM and Funk, J and Marsh, TL and Mulks, MH}, title = {Development of the tonsillar microbiome in pigs from newborn through weaning.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {35}, pmid = {29661149}, issn = {1471-2180}, abstract = {BACKGROUND: Porcine tonsils are lympho-epithelial tissues, colonized by numerous bacteria and viruses, that act as a reservoir for both host-specific pathogens and zoonotic pathogens with a high potential of transmission to humans. There are no existing studies describing the development of the tonsillar microbiome. We sequenced 16S rRNA genes from tonsillar samples of pigs to follow the development of the microbial communities from birth through weaning. Samples derived from sows were also analyzed to determine potential sources for the tonsil microbiome in piglets.

RESULTS: The composition of the newborn piglet tonsil microbiome could be differentiated by litter and had strong similarity to the sow teat skin as well as sow vaginal microbiome. The tonsil microbiome in these young piglets was mainly dominated by members of the Pasteurellaceae, Moraxellaceae, and Streptococcaceae families, while there were some transient members of the microbiome that were abundant at specific times, such as Staphylococcaceae in newborns and Fusobacteriaceae and Leptotrichiaceae in weeks 2 and 3. The microbiome initially differed between litters but over the following 3 weeks the communities of different litters converged in composition and then diverged in week 4 due to a combination of changes and stresses associated with weaning, including a shift from milk to a solid diet, in-feed Carbadox® and room change.

CONCLUSIONS: A significant portion of the tonsil microbiome was acquired either at birth from the sow vaginal tract or within a few hours post-birth from the sow teat skin. Our data demonstrate a temporal succession in the development of the pig tonsillar microbiome through the first weeks of life, with a convergence in the composition of the microbiome in all piglets by 3 weeks of age. The combination of management practices associated with weaning coincided with dramatic shifts in the tonsillar microbiome.}, } @article {pmid29661148, year = {2018}, author = {Ren, Y and Reddy, JS and Pottier, C and Sarangi, V and Tian, S and Sinnwell, JP and McDonnell, SK and Biernacka, JM and Carrasquillo, MM and Ross, OA and Ertekin-Taner, N and Rademakers, R and Hudson, M and Mainzer, LS and Asmann, YW}, title = {Identification of missing variants by combining multiple analytic pipelines.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {139}, pmid = {29661148}, issn = {1471-2105}, support = {R35 NS097261-01/NH/NIH HHS/United States ; R01 NS080820/NH/NIH HHS/United States ; R35 NS097261/NS/NINDS NIH HHS/United States ; RF1 AG051504/AG/NIA NIH HHS/United States ; R01 NS080820/NS/NINDS NIH HHS/United States ; U01 AG046139/NH/NIH HHS/United States ; U01 AG046139/AG/NIA NIH HHS/United States ; RF1 AG051504/NH/NIH HHS/United States ; }, mesh = {Alzheimer Disease/genetics ; Base Composition/genetics ; Computational Biology/*methods ; Drug Discovery ; *Genetic Variation ; Genome ; Genotype ; Genotyping Techniques ; Humans ; Sample Size ; Sequence Alignment ; }, abstract = {BACKGROUND: After decades of identifying risk factors using array-based genome-wide association studies (GWAS), genetic research of complex diseases has shifted to sequencing-based rare variants discovery. This requires large sample sizes for statistical power and has brought up questions about whether the current variant calling practices are adequate for large cohorts. It is well-known that there are discrepancies between variants called by different pipelines, and that using a single pipeline always misses true variants exclusively identifiable by other pipelines. Nonetheless, it is common practice today to call variants by one pipeline due to computational cost and assume that false negative calls are a small percent of total.

RESULTS: We analyzed 10,000 exomes from the Alzheimer's Disease Sequencing Project (ADSP) using multiple analytic pipelines consisting of different read aligners and variant calling strategies. We compared variants identified by using two aligners in 50,100, 200, 500, 1000, and 1952 samples; and compared variants identified by adding single-sample genotyping to the default multi-sample joint genotyping in 50,100, 500, 2000, 5000 and 10,000 samples. We found that using a single pipeline missed increasing numbers of high-quality variants correlated with sample sizes. By combining two read aligners and two variant calling strategies, we rescued 30% of pass-QC variants at sample size of 2000, and 56% at 10,000 samples. The rescued variants had higher proportions of low frequency (minor allele frequency [MAF] 1-5%) and rare (MAF < 1%) variants, which are the very type of variants of interest. In 660 Alzheimer's disease cases with earlier onset ages of ≤65, 4 out of 13 (31%) previously-published rare pathogenic and protective mutations in APP, PSEN1, and PSEN2 genes were undetected by the default one-pipeline approach but recovered by the multi-pipeline approach.

CONCLUSIONS: Identification of the complete variant set from sequencing data is the prerequisite of genetic association analyses. The current analytic practice of calling genetic variants from sequencing data using a single bioinformatics pipeline is no longer adequate with the increasingly large projects. The number and percentage of quality variants that passed quality filters but are missed by the one-pipeline approach rapidly increased with sample size.}, } @article {pmid29661147, year = {2018}, author = {Holtz, MD and Hwang, SF and Strelkov, SE}, title = {Genotyping of Plasmodiophora brassicae reveals the presence of distinct populations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {254}, pmid = {29661147}, issn = {1471-2164}, support = {CARP 2015.14//Canola Council of Canada/ ; }, mesh = {Genetic Variation ; Genotyping Techniques ; Plasmodiophorida/classification/*genetics/pathogenicity ; Sequence Analysis, DNA ; Virulence/genetics ; }, abstract = {BACKGROUND: Plasmodiophora brassicae is a soilborne pathogen of the family Brassicaceae and the causal agent of clubroot disease. In Canada, P. brassicae is now one of the most important constraints to canola (Brassica napus) production, and is managed mainly by the deployment of resistant cultivars. In recent years, however, new strains of the pathogen have emerged that are capable of overcoming host resistance, posing new challenges for disease management. Despite its economic significance, molecular studies of P. brassicae are rare, mainly because this microorganism cannot be cultured outside of its host.

RESULTS: Restriction site-associated DNA sequencing (RADseq) was used to examine the genetic diversity within P. brassicae single-spore and field isolates collected from across Canada. The isolates included individuals that were either capable or incapable of causing disease on clubroot resistant canola cultivars. Over 8750 variants were identified through RADseq. Population analysis indicated that most isolates belonged to one of two distinct populations, corresponding with the ability of isolates to cause disease on resistant cultivars. Within each population, there were low levels of genetic diversity. One thousand and fifty of the genetic variants that distinguished the two populations were nonsynonymous, altering the coding sequences of genes.

CONCLUSION: The application of RADseq revealed two distinct populations of P. brassicae in Canada, suggesting multiple introductions of the pathogen into the country. The genetic variation found here will be important for future research and monitoring of the pathogen.}, } @article {pmid29661146, year = {2018}, author = {Duwadi, K and Austin, RS and Mainali, HR and Bett, K and Marsolais, F and Dhaubhadel, S}, title = {Slow darkening of pinto bean seed coat is associated with significant metabolite and transcript differences related to proanthocyanidin biosynthesis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {260}, pmid = {29661146}, issn = {1471-2164}, support = {J-001331//Agriculture and Agri-Food Canada (CA)/ ; }, mesh = {Gene Expression Profiling ; Phaseolus/*genetics/*metabolism ; *Pigmentation ; Proanthocyanidins/*biosynthesis ; RNA, Messenger/genetics/metabolism ; Seeds/*metabolism ; }, abstract = {BACKGROUND: Postharvest seed coat darkening in pinto bean is an undesirable trait resulting in a loss in the economic value of the crop. The extent of darkening varies between the bean cultivars and their storage conditions.

RESULTS: Metabolite analysis revealed that the majority of flavonoids including proanthocyanidin monomer catechin accumulated at higher level in a regular darkening (RD) pinto line CDC Pintium than in a slow darkening (SD) line 1533-15. A transcriptome analysis was conducted to compare gene expression between CDC Pintium and 1533-15 and identify the gene (s) that may play a role in slow darkening processes in 1533-15 pinto. RNAseq against total RNA from RD and SD cultivars found several phenylpropanoid genes, metabolite transporter genes and genes involved in gene regulation or modification to be differentially expressed between CDC Pintium and 1533-15.

CONCLUSION: RNAseq analysis and metabolite data of seed coat tissue from CDC Pintium and 1533-15 revealed that the whole proanthocyanidin biosynthetic pathway was downregulated in 1533-15. Additionally, genes that encode for putative transporter proteins were also downregulated in 1533-15 suggesting both synthesis and accumulation of proanthocyanidin is reduced in SD pintos.}, } @article {pmid29661140, year = {2018}, author = {Gruber, M and Alahakoon, U and Taheri, A and Nagubushana, N and Zhou, R and Aung, B and Sharpe, A and Hannoufa, A and Bonham-Smith, P and Hegedus D, DD}, title = {The biochemical composition and transcriptome of cotyledons from Brassica napus lines expressing the AtGL3 transcription factor and exhibiting reduced flea beetle feeding.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {64}, pmid = {29661140}, issn = {1471-2229}, mesh = {Animals ; Arabidopsis Proteins/genetics/metabolism ; Brassica napus/genetics/*metabolism/*parasitology ; Coleoptera/*pathogenicity ; Cotyledon/genetics/*metabolism/*parasitology ; Gene Expression Regulation, Plant ; Glucosinolates/metabolism ; Plant Proteins/genetics/metabolism ; Transcription Factors/genetics/*metabolism ; Transcriptome/*genetics ; Trichomes/genetics/metabolism/parasitology ; }, abstract = {BACKGROUND: Previously, transgenic trichome-bearing (hairy leaf) Brassica napus lines expressing either the Arabidopsis thaliana GL3 gene (line AtGL3+) [1] or the AtGL3 gene in combination with an RNAi construct to down-regulate TTG1 (line K-5-8) [2] were developed. The leaves of these lines exhibited altered insect feeding (flea beetle) and oviposition (diamondback moth) behaviour compared to the non-transgenic semi-glabrous leaves of B. napus cv. Westar. Interestingly, the cotyledons of these lines remained glabrous, but also showed reduced feeding by flea beetles. Here we examine the composition and global transcriptome of the glabrous cotyledons from these transgenic lines to ascertain the mechanism(s) underlying this unexpected phenomenon.

RESULTS: Approximately, 7500 genes were up-regulated in cotyledons of each hairy line, compared with < 30 that were down-regulated. The up-regulated genes included those involved in cell wall synthesis, secondary metabolite production, redox, stress and hormone-related responses that have the potential to impact host plant cues required to elicit defense responses toward insect pests. In particular, the expression of glucosinolate biosynthetic and degradation genes were substantially altered in the glabrous cotyledons of the two hairy leaf lines. The transcriptomic data was supported by glucosinolate and cell wall composition profiles of the cotyledons. Changes in gene expression were much more extreme in the AtGL3+ line compared with the K-5-8 line in terms of diversity and intensity.

CONCLUSIONS: The study provides a roadmap for the isolation and identification of insect resistance compounds and proteins in the glabrous cotyledons of these hairy leaf lines. It also confirms the impact of mis-expression of GL3 and TTG1 on types of metabolism other than those associated with trichomes. Finally, the large number of up-regulated genes encoding heat shock proteins, PR proteins, protease inhibitors, glucosinolate synthesis/breakdown factors, abiotic stress factors, redox proteins, transcription factors, and proteins required for auxin metabolism also suggest that these cotyledons are now primed for resistance to other forms of biotic and abiotic stress.}, } @article {pmid29661139, year = {2018}, author = {Di Cesare, A and Cabello-Yeves, PJ and Chrismas, NAM and Sánchez-Baracaldo, P and Salcher, MM and Callieri, C}, title = {Genome analysis of the freshwater planktonic Vulcanococcus limneticus sp. nov. reveals horizontal transfer of nitrogenase operon and alternative pathways of nitrogen utilization.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {259}, pmid = {29661139}, issn = {1471-2164}, mesh = {Cyanobacteria/classification/*genetics/isolation & purification/metabolism ; *Gene Transfer, Horizontal ; Genome, Bacterial ; Lakes/microbiology ; Nitrogen/*metabolism ; Nitrogenase/*genetics ; *Operon ; Phenotype ; Phylogeny ; Plankton/genetics/isolation & purification ; }, abstract = {BACKGROUND: Many cyanobacteria are capable of fixing atmospheric nitrogen, playing a crucial role in biogeochemical cycling. Little is known about freshwater unicellular cyanobacteria Synechococcus spp. at the genomic level, despite being recognised of considerable ecological importance in aquatic ecosystems. So far, it has not been shown whether these unicellular picocyanobacteria have the potential for nitrogen fixation. Here, we present the draft-genome of the new pink-pigmented Synechococcus-like strain Vulcanococcus limneticus. sp. nov., isolated from the volcanic Lake Albano (Central Italy).

RESULTS: The novel species Vulcanococcus limneticus sp. nov. falls inside the sub-cluster 5.2, close to the estuarine/marine strains in a maximum-likelihood phylogenetic tree generated with 259 marker genes with representatives from marine, brackish, euryhaline and freshwater habitats. V.limneticus sp. nov. possesses a complete nitrogenase and nif operon. In an experimental setup under nitrogen limiting and non-limiting conditions, growth was observed in both cases. However, the nitrogenase genes (nifHDK) were not transcribed, i.e., V.limneticus sp. nov. did not fix nitrogen, but instead degraded the phycobilisomes to produce sufficient amounts of ammonia. Moreover, the strain encoded many other pathways to incorporate ammonia, nitrate and sulphate, which are energetically less expensive for the cell than fixing nitrogen. The association of the nif operon to a genomic island, the relatively high amount of mobile genetic elements (52 transposases) and the lower observed GC content of V.limneticus sp. nov. nif operon (60.54%) compared to the average of the strain (68.35%) support the theory that this planktonic strain may have obtained, at some point of its evolution, the nif operon by horizontal gene transfer (HGT) from a filamentous or heterocystous cyanobacterium.

CONCLUSIONS: In this study, we describe the novel species Vulcanococcus limneticus sp. nov., which possesses a complete nif operon for nitrogen fixation. The finding that in our experimental conditions V.limneticus sp. nov. did not express the nifHDK genes led us to reconsider the actual ecological meaning of these accessory genes located in genomic island that have possibly been acquired via HGT.}, } @article {pmid29661138, year = {2018}, author = {Stead, CM and Cockrell, DC and Beare, PA and Miller, HE and Heinzen, RA}, title = {A Coxiella burnetii phospholipase A homolog pldA is required for optimal growth in macrophages and developmental form lipid remodeling.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {33}, pmid = {29661138}, issn = {1471-2180}, support = {1 Z1A AI000931 15//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/International ; }, abstract = {BACKGROUND: Many gram-negative bacteria produce an outer membrane phospholipase A (PldA) that plays an important role in outer membrane function and is associated with virulence.

RESULTS: In the current study, we characterized a pldA mutant of Coxiella burnetii, an intracellular gram-negative pathogen and the agent of human Q fever. The C. burnetti pldA open reading frame directs synthesis of a protein with conserved PldA active site residues. A C. burnetii ΔpldA deletion mutant had a significant growth defect in THP-1 macrophages, but not axenic medium, that was rescued by complementation. Thin layer chromatography was employed to assess whether pldA plays a role in remodeling membrane lipids during C. burnetii morphological differentiation. Extracted lipids were analyzed from replicating, logarithmic phase large cell variants (LCVs), non-replicating, stationary phase small cell variants (SCVs), and a mixture of LCVs and SCVs. Similar to Escherichia coli, all three forms contained cardiolipin (CL), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). However, PE and PG were present in lower quantities in the SCV while three additional lipid species were present in higher quantities. Co-migration with standards tentatively identified two of the three SCV-enriched lipids as lyso-phosphatidylethanolamine, a breakdown product of PE, and free fatty acids, which are generally toxic to bacteria. Developmental form lipid modifications required the activity of PldA.

CONCLUSIONS: Collectively, these results indicate developmentally-regulated lipid synthesis by C. burnetii contributes to colonization of macrophages and may contribute to the environmental stability and the distinct biological properties of the SCV.}, } @article {pmid29661137, year = {2018}, author = {Dutta, R and Saha-Mandal, A and Cheng, X and Qiu, S and Serpen, J and Fedorova, L and Fedorov, A}, title = {1000 human genomes carry widespread signatures of GC biased gene conversion.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {256}, pmid = {29661137}, issn = {1471-2164}, mesh = {Algorithms ; Base Composition ; Chromosomes, Human ; DNA/chemistry ; *Gene Conversion ; *Genome, Human ; Haplotypes ; Humans ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: GC-Biased Gene Conversion (gBGC) is one of the important theories put forward to explain profound long-range non-randomness in nucleotide compositions along mammalian chromosomes. Nucleotide changes due to gBGC are hard to distinguish from regular mutations. Here, we present an algorithm for analysis of millions of known SNPs that detects a subset of so-called "SNP flip-over" events representing recent gBGC nucleotide changes, which occurred in previous generations via non-crossover meiotic recombination.

RESULTS: This algorithm has been applied in a large-scale analysis of 1092 sequenced human genomes. Altogether, 56,328 regions on all autosomes have been examined, which revealed 223,955 putative gBGC cases leading to SNP flip-overs. We detected a strong bias (11.7% ± 0.2% excess) in AT- > GC over GC- > AT base pair changes within the entire set of putative gBGC cases.

CONCLUSIONS: On average, a human gamete acquires 7 SNP flip-over events, in which one allele is replaced by its complementary allele during the process of meiotic non-crossover recombination. In each meiosis event, on average, gBGC results in replacement of 7 AT base pairs by GC base pairs, while only 6 GC pairs are replaced by AT pairs. Therefore, every human gamete is enriched by one GC pair. Happening over millions of years of evolution, this bias may be a noticeable force in changing the nucleotide composition landscape along chromosomes.}, } @article {pmid29661134, year = {2018}, author = {Dias, FCF and Khan, MIR and Sirard, MA and Adams, GP and Singh, J}, title = {Transcriptome analysis of granulosa cells after conventional vs long FSH-induced superstimulation in cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {258}, pmid = {29661134}, issn = {1471-2164}, mesh = {Animals ; Cattle/*genetics/metabolism ; Female ; Follicle Stimulating Hormone/administration & dosage/*pharmacology ; Follicular Fluid/chemistry ; Gene Expression Profiling ; Granulosa Cells/drug effects/*metabolism ; Real-Time Polymerase Chain Reaction ; Superovulation ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: Prolongation of superstimulatory treatment appears to be associated with a greater superovulatory response and with greater oocyte maturation in cattle. A genome-wide bovine oligo-microarray was used to compare the gene expression of granulosa cells collected from ovarian follicles after differing durations of the growing phase induced by exogenous FSH treatment. Cows were given a conventional (4-day) or long (7-day) superstimulatory treatment (25 mg FSH im at 12-h intervals; n = 6 per group), followed by prostaglandin treatment with last FSH and LH treatment 24 h later. Granulosa cells were harvested 24 h after LH treatment.

RESULTS: The expression of 416 genes was down-regulated and 615 genes was up-regulated in the long FSH group compared to the conventional FSH group. Quantification by RT-PCR of 7 genes (NTS, PTGS2, PTX3, RGS2, INHBA, CCND2 and LRP8) supported the microarrays data. Multigene bioinformatic analysis indicates that markers of fertility and follicle maturity were up-regulated in the long FSH group.

CONCLUSION: Using the large gene expression dataset generated by the genomic analysis and our previous associated with the growth phase and gene expression changes post LH, we can conclude that a prolonged FSH-induced growing phase is associated with transcriptomic characteristics of greater follicular maturity and may therefore be more appropriate for optimizing the superovulatory response and developmental competence of oocytes in cattle.}, } @article {pmid29661132, year = {2018}, author = {Jin, Y and Olsen, RE and Østensen, MA and Gillard, GB and Korsvoll, SA and Santi, N and Gjuvsland, AB and Vik, JO and Torgersen, JS and Sandve, SR and Olsen, Y}, title = {Transcriptional development of phospholipid and lipoprotein metabolism in different intestinal regions of Atlantic salmon (Salmo salar) fry.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {253}, pmid = {29661132}, issn = {1471-2164}, support = {NFR 244164//Norges Forskningsråd/ ; }, mesh = {Animals ; Biosynthetic Pathways/genetics ; Gastric Mucosa/metabolism ; Intestinal Mucosa/*metabolism ; Intestines/growth & development ; Lipoproteins/*biosynthesis ; Organ Specificity ; Phospholipids/*biosynthesis ; Salmo salar/*genetics/growth & development/metabolism ; Stomach/growth & development ; *Transcriptome ; }, abstract = {BACKGROUND: It has been suggested that the high phospholipid (PL) requirement in Atlantic salmon (Salmo salar) fry is due to insufficient intestinal de-novo synthesis causing low lipoprotein (LP) production and reduced transport capacity of dietary lipids. However, in-depth ontogenetic analysis of intestinal PL and LP synthesis with the development of salmon has yet to be performed. Therefore, in this paper we used RNA-Seq technology to investigate the expression of genes involved in PL synthesis and LP formation throughout early developmental stages and associate insufficient expression of synthesis pathways in salmon fry with its higher dietary PL requirement. There was a special focus on the understanding homologous genes, especially those from salmonid-specific fourth vertebrate whole-genome duplication (Ss4R), and their contribution to salmonid specific features of regulation of PL metabolic pathways. Salmon fry were sampled at 0.16 g (1 day before first-feeding), 2.5 and 10 g stages of development and transcriptomic analysis was applied separately on stomach, pyloric caeca and hindgut of the fish.

RESULTS: In general, we found up-regulated pathways involved in synthesis of phosphatidylcholine (PtdCho), phosphatidylethanolamine (PtdEtn), and LP in pyloric caeca of salmon between 0.16 and 10 g. Thirteen differentially expressed genes (q < 0.05) in these pathways were highly up-regulated in 2.5 g salmon compared to 0.16 g, while only five more differentially expressed (q < 0.05) genes were found when the fish grew up to 10 g. Different homologous genes were found dominating in stomach, pyloric caeca and hindgut. However, the expression of dominating genes in pathways of PL and LP synthesis were much higher in pyloric caeca than stomach and hindgut. Salmon-specific homologous genes (Ss4R) had similar expression during development, while other homologs had more diverged expression.

CONCLUSIONS: The up-regulation of the de-novo PtdCho and PtdEtn pathways confirm that salmon have decreasing requirement for dietary PL as the fish develops. The similar expressions between Ss4R homologous genes suggest that the functional divergence of these genes was incomplete compared to homologs derived from other genome duplication. The results of the present study have provided new information on the molecular mechanisms of phospholipid synthesis and lipoprotein formation in fish.}, } @article {pmid29661131, year = {2018}, author = {Hossain, Z and Pillai, BV and Gruber, MY and Yu, M and Amyot, L and Hannoufa, A}, title = {Transcriptome profiling of Brassica napus stem sections in relation to differences in lignin content.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {255}, pmid = {29661131}, issn = {1471-2164}, mesh = {Brassica napus/enzymology/*genetics/metabolism ; Carbohydrates/biosynthesis ; Cell Wall/genetics ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Lignin/*metabolism ; Oligonucleotide Array Sequence Analysis ; Plant Stems/genetics/metabolism ; Real-Time Polymerase Chain Reaction ; Transcription Factors/genetics/metabolism ; Transcriptome ; Up-Regulation ; }, abstract = {BACKGROUND: Brassica crops are cultivated widely for human consumption and animal feed purposes, and oilseed rape/canola (Brassica napus and rapa) is the second most important oilseed worldwide. Because of its natural diversity and genetic complexity, genomics studies on oilseed rape will be a useful resource base to modify the quantity and quality of biomass in various crops, and therefore, should have a positive impact on lignocellulosic biofuel production. The objective of this study was to perform microarray analysis on two variable lignin containing oilseed rape cultivars to target novel genes and transcription factors of importance in Brassica lignin regulation for applied research.

RESULTS: To gain insight into the molecular networks controlling cell wall biosynthetic and regulatory events, we conducted lignin and microarray analysis of top and basal stem sections of brown seeded Brassica napus DH12075 and yellow seeded YN01-429 cultivars. A total of 9500 genes were differentially expressed 2-fold or higher in the stem between the cultivars, with a higher number of expressed genes in the basal section. Of the upregulated genes, many were transcription factors and a considerable number of these were associated with secondary wall synthesis and lignification in B. napus and other plant species. The three largest groups of transcription factors with differential expression were C2H2 and C3HC4 zinc fingers and bHLH. A significant number of genes related to lignin and carbohydrate metabolism also showed differential expression patterns between the stem sections of the two cultivars. Within the same cultivar, the number of upregulated genes was higher in the top section relative to the basal one.

CONCLUSION: In this study, we identified and established expression patterns of many new genes likely involved in cell wall biosynthesis and regulation. Some genes with known roles in other biochemical pathways were also identified to have a potential role in cell wall biosynthesis. This stem transcriptome profiling will allow for selecting novel regulatory and structural genes for functional characterization, a strategy which may provide tools for modifying cell wall composition to facilitate fermentation for biofuel production.}, } @article {pmid29661129, year = {2018}, author = {King, MD and Long, T and Pfalmer, DL and Andersen, TL and McDougal, OM}, title = {SPIDR: small-molecule peptide-influenced drug repurposing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {138}, pmid = {29661129}, issn = {1471-2105}, support = {0923535//National Science Foundation/International ; P20GM103408/NH/NIH HHS/United States ; DE-AC07-05ID14517//Office of Nuclear Energy/International ; 0619793//National Science Foundation/International ; P20 GM103408/GM/NIGMS NIH HHS/United States ; P20 GM109095/GM/NIGMS NIH HHS/United States ; P20GM109095/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Conotoxins/chemistry/metabolism ; *Drug Repositioning ; Ligands ; Models, Molecular ; Molecular Conformation ; Peptides/chemistry/*pharmacology ; Receptors, Nicotinic/chemistry/metabolism ; Small Molecule Libraries/*pharmacology ; *Software ; }, abstract = {BACKGROUND: Conventional de novo drug design is costly and time consuming, making it accessible to only the best resourced research organizations. An emergent approach to new drug development is drug repurposing, in which compounds that have already gone through some level of clinical testing are examined for efficacy against diseases divergent than their original application. Repurposing of existing drugs circumvents the time and considerable cost of early stages of drug development, and can be accelerated by using software to screen existing chemical databases to identify suitable drug candidates.

RESULTS: Small-molecule Peptide-Influenced Drug Repurposing (SPIDR) was developed to identify small molecule drugs that target a specific receptor by exploring the conformational binding space of peptide ligands. SPIDR was tested using the potent and selective 16-amino acid peptide α-conotoxin MII ligand and the α3β2-nicotinic acetylcholine receptor (nAChR) isoform. SPIDR incorporates a genetic algorithm-based, heuristic search procedure, which was used to explore the ligand binding domain of the α3β2-nAChR isoform using a library consisting of 640,000 α-conotoxin MII peptide analogs. The peptides that exhibited the highest affinity for α3β2-nAChR were used as models for a small-molecule structure similarity search of the PubChem Compound database. SPIDR incorporates the SimSearcher utility, which generates shape distribution signatures of molecules and employs multi-level K-means clustering to insure fast database queries. SPIDR identified non-peptide drugs with estimated binding affinities nearly double that of the native α-conotoxin MII peptide.

CONCLUSIONS: SPIDR has been generalized and integrated into DockoMatic v 2.1. This software contains an intuitive graphical interface for peptide mutant screening workflow and facilitates mapping, clustering, and searching of local molecular databases, making DockoMatic a valuable tool for researchers in drug design and repurposing.}, } @article {pmid29661000, year = {2018}, author = {Mettlen, M and Chen, PH and Srinivasan, S and Danuser, G and Schmid, SL}, title = {Regulation of Clathrin-Mediated Endocytosis.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {871-896}, doi = {10.1146/annurev-biochem-062917-012644}, pmid = {29661000}, issn = {1545-4509}, support = {R01 MH061345/MH/NIMH NIH HHS/United States ; }, abstract = {Clathrin-mediated endocytosis (CME) is the major endocytic pathway in mammalian cells. It is responsible for the uptake of transmembrane receptors and transporters, for remodeling plasma membrane composition in response to environmental changes, and for regulating cell surface signaling. CME occurs via the assembly and maturation of clathrin-coated pits that concentrate cargo as they invaginate and pinch off to form clathrin-coated vesicles. In addition to the major coat proteins, clathrin triskelia and adaptor protein complexes, CME requires a myriad of endocytic accessory proteins and phosphatidylinositol lipids. CME is regulated at multiple steps-initiation, cargo selection, maturation, and fission-and is monitored by an endocytic checkpoint that induces disassembly of defective pits. Regulation occurs via posttranslational modifications, allosteric conformational changes, and isoform and splice-variant differences among components of the CME machinery, including the GTPase dynamin. This review summarizes recent findings on the regulation of CME and the evolution of this complex process.}, } @article {pmid29660313, year = {2018}, author = {Kasemeier-Kulesa, JC and Kulesa, PM}, title = {The convergent roles of CD271/p75 in neural crest-derived melanoma plasticity.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29660313}, issn = {1095-564X}, support = {R21 NS092001/NS/NINDS NIH HHS/United States ; }, abstract = {The embryonic microenvironment is an important source of signals that promote multipotent cells to adopt a specific fate and direct cells along distinct migratory pathways. Yet, the ability of the embryonic microenvironment to retain multipotent progenitors or reprogram de-differentiated cells is less clear. Mistakes in cell differentiation or migration often result in developmental defects and tumorigenesis, including aggressive cancers that share many characteristics with embryonic progenitor cells. This is a striking feature of the vertebrate neural crest, a multipotent and highly migratory cell population first identified by His (1868) with the potential to metamorphose into aggressive melanoma cancer. In this perspective, we address the roles of CD271/p75 in tumor initiation, phenotype switching and reprogramming of metastatic melanoma and discuss the convergence of these roles in melanoma plasticity.}, } @article {pmid29660312, year = {2018}, author = {Sriskanthadevan-Pirahas, S and Lee, J and Grewal, SS}, title = {The EGF/Ras pathway controls growth in Drosophila via ribosomal RNA synthesis.}, journal = {Developmental biology}, volume = {439}, number = {1}, pages = {19-29}, doi = {10.1016/j.ydbio.2018.04.006}, pmid = {29660312}, issn = {1095-564X}, support = {P40 OD018537/OD/NIH HHS/United States ; MOP-86622//CIHR/Canada ; PJT-152892//CIHR/Canada ; }, mesh = {Animals ; Cell Proliferation ; Drosophila/genetics/metabolism ; Drosophila Proteins/genetics/metabolism/*physiology ; Epidermal Growth Factor/metabolism/*physiology ; Gene Expression Regulation/physiology ; IMP Dehydrogenase/metabolism/*physiology ; Larva/metabolism ; RNA, Ribosomal/*biosynthesis/metabolism/physiology ; Ribosomes/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Transcription, Genetic/physiology ; }, abstract = {The Ras small G-protein is a conserved regulator of cell and tissue growth during animal development. Studies in Drosophila have shown how Ras can stimulate a RAF-MEK-ERK signalling pathway to control cell growth and proliferation in response to Epidermal Growth Factor (EGF) stimulation. This work has also defined several transcription factors that can function as downstream growth effectors of the EGF/Ras/ERK pathway by stimulating mRNA transcription. Here we report on stimulation of RNA polymerase I (Pol I)-mediated ribosomal RNA (rRNA) synthesis as a growth effector of Ras/ERK signalling in Drosophila. We show that Ras/ERK signalling promotes an increase in nucleolar size in larval wing discs, which is indicative of increased ribosome synthesis. We also find that activation of Ras/ERK signalling promotes rRNA synthesis both in vivo and in cultured Drosophila S2 cells. We show that Ras signalling can regulate the expression of the Pol I transcription factor TIF-IA, and that this regulation requires dMyc. Finally, we find that TIF-IA-mediated rRNA synthesis is required for Ras/ERK signalling to drive proliferation in both larval and adult Drosophila tissues. These findings indicate that Ras signalling can promote ribosome synthesis in Drosophila, and that this is one mechanism that contributes to the growth effects of the Ras signalling pathway.}, } @article {pmid29660002, year = {2018}, author = {Alié, A and Hiebert, LS and Simion, P and Scelzo, M and Prünster, MM and Lotito, S and Delsuc, F and Douzery, EJP and Dantec, C and Lemaire, P and Darras, S and Kawamura, K and Brown, FD and Tiozzo, S}, title = {Convergent Acquisition of Nonembryonic Development in Styelid Ascidians.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1728-1743}, pmid = {29660002}, issn = {1537-1719}, abstract = {Asexual propagation and whole body regeneration are forms of nonembryonic development (NED) widespread across animal phyla and central in life history and evolutionary diversification of metazoans. Whereas it is challenging to reconstruct the gains or losses of NED at large phylogenetic scale, comparative studies could benefit from being conducted at more restricted taxonomic scale, in groups for which phylogenetic relationships are well established. The ascidian family of Styelidae encompasses strictly sexually reproducing solitary forms as well as colonial species that combine sexual reproduction with different forms of NED. To date, the phylogenetic relationships between colonial and solitary styelids remain controversial and so is the pattern of NED evolution. In this study, we built an original pipeline to combine eight genomes with 18 de novo assembled transcriptomes and constructed data sets of unambiguously orthologous genes. Using a phylogenomic super-matrix of 4,908 genes from these 26 tunicates we provided a robust phylogeny of this family of chordates, which supports two convergent acquisitions of NED. This result prompted us to further describe the budding process in the species Polyandrocarpa zorritensis, leading to the discovery of a novel mechanism of asexual development. Whereas the pipeline and the data sets produced can be used for further phylogenetic reconstructions in tunicates, the phylogeny provided here sets an evolutionary framework for future experimental studies on the emergence and disappearance of complex characters such as asexual propagation and whole body regeneration.}, } @article {pmid29659993, year = {2018}, author = {Zhang, J}, title = {Neutral Theory and Phenotypic Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1327-1331}, pmid = {29659993}, issn = {1537-1719}, support = {R01 GM120093/GM/NIGMS NIH HHS/United States ; }, abstract = {Although the neutral theory of molecular evolution was proposed to explain DNA and protein sequence evolution, in principle it could also explain phenotypic evolution. Nevertheless, overall, phenotypes should be less likely than genotypes to evolve neutrally. I propose that, when phenotypic traits are stratified according to a hierarchy of biological organization, the fraction of evolutionary changes in phenotype that are adaptive rises with the phenotypic level considered. Consistently, molecular traits are frequently found to evolve neutrally whereas a large, random set of organismal traits were recently reported to vary largely adaptively. Many more studies of unbiased samples of phenotypic traits are needed to test the general validity of this hypothesis.}, } @article {pmid29659992, year = {2018}, author = {Austerlitz, F and Heyer, E}, title = {Neutral Theory: From Complex Population History to Natural Selection and Sociocultural Phenomena in Human Populations.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1304-1307}, doi = {10.1093/molbev/msy067}, pmid = {29659992}, issn = {1537-1719}, abstract = {Here, we present a synthetic view on how Kimura's Neutral theory has helped us gaining insight on the different evolutionary forces that shape human evolution. We put this perspective in the frame of recent emerging challenges: the use of whole genome data for reconstructing population histories, natural selection on complex polygenic traits, and integrating cultural processes in human evolution.}, } @article {pmid29659991, year = {2018}, author = {Bast, J and Parker, DJ and Dumas, Z and Jalvingh, KM and Tran Van, P and Jaron, KS and Figuet, E and Brandt, A and Galtier, N and Schwander, T}, title = {Consequences of Asexuality in Natural Populations: Insights from Stick Insects.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1668-1677}, pmid = {29659991}, issn = {1537-1719}, abstract = {Recombination is a fundamental process with significant impacts on genome evolution. Predicted consequences of the loss of recombination include a reduced effectiveness of selection, changes in the amount of neutral polymorphisms segregating in populations, and an arrest of GC-biased gene conversion. Although these consequences are empirically well documented for nonrecombining genome portions, it remains largely unknown if they extend to the whole genome scale in asexual organisms. We identify the consequences of asexuality using de novo transcriptomes of five independently derived, obligately asexual lineages of stick insects, and their sexual sister-species. We find strong evidence for higher rates of deleterious mutation accumulation, lower levels of segregating polymorphisms and arrested GC-biased gene conversion in asexuals as compared with sexuals. Taken together, our study conclusively shows that predicted consequences of genome evolution under asexuality can indeed be found in natural populations.}, } @article {pmid29659989, year = {2018}, author = {Tagliacollo, VA and Lanfear, R}, title = {Estimating Improved Partitioning Schemes for Ultraconserved Elements.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1798-1811}, pmid = {29659989}, issn = {1537-1719}, abstract = {Ultraconserved (UCEs) are popular markers for phylogenomic studies. They are relatively simple to collect from distantly-related organisms, and contain sufficient information to infer relationships at almost all taxonomic levels. Most studies of UCEs use partitioning to account for variation in rates and patterns of molecular evolution among sites, for example by estimating an independent model of molecular evolution for each UCE. However, rates and patterns of molecular evolution vary substantially within as well as between UCEs, suggesting that there may be opportunities to improve how UCEs are partitioned for phylogenetic inference. We propose and evaluate new partitioning methods for phylogenomic studies of UCEs: Sliding-Window Site Characteristics (SWSC), and UCE Site Position (UCESP). The first method uses site characteristics such as entropy, multinomial likelihood, and GC content to generate partitions that account for heterogeneity in rates and patterns of molecular evolution within each UCE. The second method groups together nucleotides that are found in similar physical locations within the UCEs. We examined the new methods with seven published data sets from a variety of taxa. We demonstrate the UCESP method generates partitions that are worse than other strategies used to partition UCE data sets (e.g., one partition per UCE). The SWSC method, particularly when based on site entropies, generates partitions that account for within-UCE heterogeneity and leads to large increases in the model fit. All of the methods, code, and data used in this study, are available from https://github.com/Tagliacollo/PartitionUCE. Simplified code for implementing the best method, the SWSC-EN, is available from https://github.com/Tagliacollo/PFinderUCE-SWSC-EN.}, } @article {pmid29659984, year = {2018}, author = {}, title = {Molecular Biology and Evolution, Volume 35, Issue 4.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1821}, doi = {10.1093/molbev/msy057}, pmid = {29659984}, issn = {1537-1719}, } @article {pmid29659981, year = {2018}, author = {Charlesworth, B and Charlesworth, D}, title = {Neutral Variation in the Context of Selection.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1359-1361}, doi = {10.1093/molbev/msy062}, pmid = {29659981}, issn = {1537-1719}, abstract = {In its initial formulation by Motoo Kimura, the neutral theory was concerned solely with the level of variability maintained by random genetic drift of selectively neutral mutations, and the rate of molecular evolution caused by the fixation of such mutations. The original theory considered events at a single genetic locus in isolation from the rest of the genome. It did not take long, however, for theoreticians to wonder whether selection at one or more loci might influence neutral variability at linked sites. Once DNA sequence variability could be studied, and especially when resequencing of whole genomes became possible, it became clear that patterns of neutral variability in genomes are affected by selection at linked sites, and that these patterns could advance our understanding of natural selection, and can be used to detect the action of selection in genomic regions, including selection much weaker than could be detected by direct measurements of the relative fitnesses of different genotypes. We outline the different types of processes that have been studied, in approximate order of their historical development.}, } @article {pmid29659975, year = {2018}, author = {Borba, AR and Serra, TS and Górska, A and Gouveia, P and Cordeiro, AM and Reyna-Llorens, I and Knerová, J and Barros, PM and Abreu, IA and Oliveira, MM and Hibberd, JM and Saibo, NJM}, title = {Synergistic Binding of bHLH Transcription Factors to the Promoter of the Maize NADP-ME Gene Used in C4 Photosynthesis Is Based on an Ancient Code Found in the Ancestral C3 State.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1690-1705}, pmid = {29659975}, issn = {1537-1719}, abstract = {C4 photosynthesis has evolved repeatedly from the ancestral C3 state to generate a carbon concentrating mechanism that increases photosynthetic efficiency. This specialized form of photosynthesis is particularly common in the PACMAD clade of grasses, and is used by many of the world's most productive crops. The C4 cycle is accomplished through cell-type-specific accumulation of enzymes but cis-elements and transcription factors controlling C4 photosynthesis remain largely unknown. Using the NADP-Malic Enzyme (NADP-ME) gene as a model we tested whether mechanisms impacting on transcription in C4 plants evolved from ancestral components found in C3 species. Two basic Helix-Loop-Helix (bHLH) transcription factors, ZmbHLH128 and ZmbHLH129, were shown to bind the C4NADP-ME promoter from maize. These proteins form heterodimers and ZmbHLH129 impairs trans-activation by ZmbHLH128. Electrophoretic mobility shift assays indicate that a pair of cis-elements separated by a seven base pair spacer synergistically bind either ZmbHLH128 or ZmbHLH129. This pair of cis-elements is found in both C3 and C4 Panicoid grass species of the PACMAD clade. Our analysis is consistent with this cis-element pair originating from a single motif present in the ancestral C3 state. We conclude that C4 photosynthesis has co-opted an ancient C3 regulatory code built on G-box recognition by bHLH to regulate the NADP-ME gene. More broadly, our findings also contribute to the understanding of gene regulatory networks controlling C4 photosynthesis.}, } @article {pmid29659974, year = {2018}, author = {Chan, CX and Vaysberg, P and Price, DC and Pelletreau, KN and Rumpho, ME and Bhattacharya, D}, title = {Active Host Response to Algal Symbionts in the Sea Slug Elysia chlorotica.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1706-1711}, doi = {10.1093/molbev/msy061}, pmid = {29659974}, issn = {1537-1719}, abstract = {Sacoglossan sea slugs offer fascinating systems to study the onset and persistence of algal-plastid symbioses. Elysia chlorotica is particularly noteworthy because it can survive for months, relying solely on energy produced by ingested plastids of the stramenopile alga Vaucheria litorea that are sequestered in cells lining its digestive diverticula. How this animal can maintain the actively photosynthesizing organelles without replenishment of proteins from the lost algal nucleus remains unknown. Here, we used RNA-Seq analysis to test the idea that plastid sequestration leaves a significant signature on host gene expression during E. chlorotica development. Our results support this hypothesis and show that upon exposure to and ingestion of V. litorea plastids, genes involved in microbe-associated molecular patterns and oxidative stress-response mechanisms are significantly up-regulated. Interestingly, our results with E. chlorotica mirror those found with corals that maintain dinoflagellates as intact cells in symbiosomes, suggesting parallels between these animal-algal symbiotic interactions.}, } @article {pmid29659972, year = {2018}, author = {Niimura, Y and Matsui, A and Touhara, K}, title = {Acceleration of Olfactory Receptor Gene Loss in Primate Evolution: Possible Link to Anatomical Change in Sensory Systems and Dietary Transition.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1437-1450}, doi = {10.1093/molbev/msy042}, pmid = {29659972}, issn = {1537-1719}, abstract = {Primates have traditionally been regarded as vision-oriented animals with low olfactory ability, though this "microsmatic primates" view has been challenged recently. To clarify when and how degeneration of the olfactory system occurred and to specify the relevant factors during primate evolution, we here examined the olfactory receptor (OR) genes from 24 phylogenetically and ecologically diverse primate species. The results revealed that strepsirrhines with curved noses had functional OR gene repertoires that were nearly twice as large as those for haplorhines with simple noses. Neither activity pattern (nocturnal/diurnal) nor color vision system showed significant correlation with the number of functional OR genes while phylogeny and nose structure (haplorhine/strepsirrhine) are statistically controlled, but extent of folivory did. We traced the evolutionary fates of individual OR genes by identifying orthologous gene groups, demonstrating that the rates of OR gene losses were accelerated at the ancestral branch of haplorhines, which coincided with the acquisition of acute vision. The highest rate of OR gene loss was observed at the ancestral branch of leaf-eating colobines; this reduction is possibly linked with the dietary transition from frugivory to folivory because odor information is essential for fruit foraging but less so for leaf foraging. Intriguingly, we found accelerations of OR gene losses in an external branch to every hominoid species examined. These findings suggest that the current OR gene repertoire in each species has been shaped by a complex interplay of phylogeny, anatomy, and habitat; therefore, multiple factors may contribute to the olfactory degeneration in primates.}, } @article {pmid29659942, year = {2018}, author = {Vdacný, P}, title = {Evolutionary Associations of Endosymbiotic Ciliates Shed Light on the Timing of the Marsupial-Placental Split.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1757-1769}, pmid = {29659942}, issn = {1537-1719}, abstract = {Trichostome ciliates are among the most conspicuous protists in the gastrointestinal tract of a large variety of vertebrates. However, little is still known about phylogeny of the trichostome/vertebrate symbiotic systems, evolutionary correlations between trichostome extrinsic traits, and character-dependent diversification of trichostomes. These issues were investigated here, using the relaxed molecular clock technique along with stochastic mapping of character evolution, and binary-state speciation and extinction models. Clock analyses revealed that trichostomes colonized the vertebrate gastrointestinal tract ∼135 Ma, that is, near the paleontological minimum for the split of therian mammals into marsupials and placentals. According to stochastic mapping, the last common ancestor of trichostomes most likely invaded the hindgut of a mammal. Although multiple shifts to fish/amphibian or avian hosts and to the foregut compartments took place during the trichostome phylogeny, only transition to the foregut was recognized as a key innovation responsible for the explosive radiation of ophryoscolecid trichostomes after the Cretaceous/Tertiary boundary, when ungulates began their diversification. Since crown radiations of main trichostome lineages follow those of their mammalian hosts and are in agreement with their historic dispersal routes, the present time-calibrated phylogeny might help to elucidate controversies in the geological and molecular timing of the split between marsupials and placental mammals.}, } @article {pmid29659817, year = {2018}, author = {Pulkkinen, K and Pekkala, N and Ashrafi, R and Hämäläinen, DM and Nkembeng, AN and Lipponen, A and Hiltunen, T and Valkonen, JK and Taskinen, J}, title = {Effect of resource availability on evolution of virulence and competition in an environmentally transmitted pathogen.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy060}, pmid = {29659817}, issn = {1574-6941}, abstract = {Understanding ecological and epidemiological factors driving pathogen evolution in contemporary time scales is a major challenge in modern health management. Pathogens that replicate outside the hosts are subject to selection imposed by ambient environmental conditions. Increased nutrient levels could increase pathogen virulence by pre-adapting for efficient use of resources upon contact to a nutrient rich host or by favouring transmission of fast-growing virulent strains. We measured changes in virulence and competition in Flavobacterium columnare, a bacterial pathogen of freshwater fish, under high and low nutrient levels. To test competition between strains in genotype mixtures, we developed a quantitative real-time PCR assay. We found that a virulent strain maintained its virulence and outcompeted less virulent strains independent of the nutrient level and resource renewal rate while a less virulent strain further lost virulence in chemostats under low nutrient level and over long-term serial culture under high nutrient level. Our results suggest that increased outside-host nutrient levels might maintain virulence in less virulent strains and increase their contribution to epidemics in aquaculture. The results highlight a need to further explore the role of resource in the outside-host environment in maintaining strain diversity and driving evolution of virulence among environmentally growing pathogens.}, } @article {pmid29659815, year = {2018}, author = {Morata, J and Marín, F and Payet, J and Casacuberta, JM}, title = {Plant Lineage-Specific Amplification of Transcription Factor Binding Motifs by Miniature Inverted-Repeat Transposable Elements (MITEs).}, journal = {Genome biology and evolution}, volume = {10}, number = {5}, pages = {1210-1220}, pmid = {29659815}, issn = {1759-6653}, mesh = {Base Sequence ; Binding Sites ; DNA Repeat Expansion ; DNA Transposable Elements/*genetics ; Gene Regulatory Networks ; Genetic Speciation ; Genome, Plant/genetics ; Genomics ; Inverted Repeat Sequences/*genetics ; Lycopersicon esculentum/genetics ; Plant Proteins/genetics ; Prunus/genetics ; Prunus persica/*genetics ; Regulatory Elements, Transcriptional/*genetics ; Transcription Factors/*metabolism ; }, abstract = {Transposable elements are one of the main drivers of plant genome evolution. Transposon insertions can modify the gene coding capacity or the regulation of their expression, the latter being a more subtle effect, and therefore particularly useful for evolution. Transposons have been show to contain transcription factor binding sites that can be mobilized upon transposition with the potential to integrate new genes into transcriptional networks. Miniature inverted-repeat transposable elements (MITEs) are a type of noncoding DNA transposons that could be particularly suited as a vector to mobilize transcription factor binding sites and modify transcriptional networks during evolution. MITEs are small in comparison to other transposons and can be excised, which should make them less mutagenic when inserting into promoters. On the other hand, in spite of their cut-and-paste mechanisms of transposition, they can reach very high copy numbers in genomes. We have previously shown that MITEs have amplified and redistributed the binding motif of the E2F transcription factor in different Brassicas. Here, we show that MITEs have amplified and mobilized the binding motifs of the bZIP60 and PIF3 transcription factors in peach and Prunus mume, and the TCP15/23 binding motif in tomato. Our results suggest that MITEs could have rewired new genes into transcriptional regulatory networks that are responsible for important adaptive responses and breeding traits in plants, such as stress responses, flowering time, or fruit ripening. The results presented here therefore suggest a general impact of MITEs in the evolution of transcriptional regulatory networks in plants.}, } @article {pmid29659811, year = {2018}, author = {Tohya, M and Sekizaki, T and Miyoshi-Akiyama, T}, title = {Complete Genome Sequence of Streptococcus ruminantium sp. nov. GUT-187T (=DSM 104980T =JCM 31869T), the Type Strain of S. ruminantium, and Comparison with Genome Sequences of Streptococcus suis Strains.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1180-1184}, pmid = {29659811}, issn = {1759-6653}, mesh = {Animals ; Base Sequence ; Genome/genetics ; *Molecular Sequence Annotation ; Phylogeny ; Sequence Analysis, DNA ; Streptococcal Infections/*genetics/microbiology ; Streptococcus/*genetics ; Streptococcus suis/genetics ; *Whole Genome Sequencing ; }, abstract = {Streptococcus ruminantium sp. nov. of type strain GUT-187T, previously classified as Streptococcus suis serotype 33, is a recently described novel streptococcal species. This study was designed to determine the complete genome sequence of S. ruminantium GUT-187T using a combination of Oxford Nanopore and the Illumina platform, and to compare this sequence with the genomes of 27 S. suis representative strains. The genome of GUT-187T was 2,090,539 bp in size, with a GC content of 40.01%. This genome contained 1,961 predicted protein coding DNA sequences (CDSs); of these, 1,685 (85.9%) showed similarity with S. suis CDSs. Of the remaining 276 CDSs, 81 (29.3%) showed some degree of similarity with CDSs of other streptococcal species. The genome of GUT-187T contained no intact prophage. The numbers of prophages and CRISPR spacers, as well as the presence or absence of genes encoding CRISPR-associated proteins, differed in S. ruminantium and S. suis. A phylogenetic analysis indicates that GUT-187T may be outgroup to the S. suis strains in our sample, thereby justifying its classification as distinct species. Gene mapping indicated 10.2 times of massive genome rearrangements in average occurred between S. ruminantium and S. suis. There was no significant statistical difference in clusters of orthologous group distribution between S. ruminantium and S. suis.}, } @article {pmid29659810, year = {2018}, author = {Hill, PL and Burridge, CP and Ezaz, T and Wapstra, E}, title = {Conservation of Sex-Linked Markers among Conspecific Populations of a Viviparous Skink, Niveoscincus ocellatus, Exhibiting Genetic and Temperature-Dependent Sex Determination.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1079-1087}, pmid = {29659810}, issn = {1759-6653}, mesh = {Animals ; *Biological Evolution ; Female ; Lizards/*genetics ; Male ; Sex Chromosomes/*genetics ; Sex Determination Processes/*genetics ; Temperature ; Viviparity, Nonmammalian/genetics ; }, abstract = {Sex determination systems are exceptionally diverse and have undergone multiple and independent evolutionary transitions among species, particularly reptiles. However, the mechanisms underlying these transitions have not been established. Here, we tested for differences in sex-linked markers in the only known reptile that is polymorphic for sex determination system, the spotted snow skink, Niveoscincus ocellatus, to quantify the genomic differences that have accompanied this transition. In a highland population, sex is determined genetically, whereas in a lowland population, offspring sex ratio is influenced by temperature. We found a similar number of sex-linked loci in each population, including shared loci, with genotypes consistent with male heterogamety (XY). However, population-specific linkage disequilibrium suggests greater differentiation of sex chromosomes in the highland population. Our results suggest that transitions between sex determination systems can be facilitated by subtle genetic differences.}, } @article {pmid29659807, year = {2018}, author = {Floriano, AM and Castelli, M and Krenek, S and Berendonk, TU and Bazzocchi, C and Petroni, G and Sassera, D}, title = {The Genome Sequence of "Candidatus Fokinia solitaria": Insights on Reductive Evolution in Rickettsiales.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1120-1126}, pmid = {29659807}, issn = {1759-6653}, mesh = {Animals ; Chromosome Mapping ; Citric Acid Cycle/genetics ; Cytoplasm/genetics ; *Evolution, Molecular ; Genome, Bacterial/genetics ; Paramecium/*genetics/microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rickettsieae/*genetics ; Symbiosis/genetics ; }, abstract = {"Candidatus Fokinia solitaria" is an obligate intracellular endosymbiont of a unicellular eukaryote, a ciliate of the genus Paramecium. Here, we present the genome sequence of this bacterium and subsequent analysis. Phylogenomic analysis confirmed the previously reported positioning of the symbiont within the "Candidatus Midichloriaceae" family (order Rickettsiales), as well as its high sequence divergence from other members of the family, indicative of fast sequence evolution. Consistently with this high evolutionary rate, a comparative genomic analysis revealed that the genome of this symbiont is the smallest of the Rickettsiales to date. The reduced genome does not present flagellar genes, nor the pathway for the biosynthesis of lipopolysaccharides (present in all the other so far sequenced members of the family "Candidatus Midichloriaceae") or genes for the Krebs cycle (present, although not always complete, in Rickettsiales). These results indicate an evolutionary trend toward a stronger dependence on the host, in comparison with other members of the family. Two alternative scenarios are compatible with our results; "Candidatus Fokinia solitaria" could be either a recently evolved, vertically transmitted mutualist, or a parasite with a high host-specificity.}, } @article {pmid29659796, year = {2018}, author = {Müller, H and Sib, E and Gajdiss, M and Klanke, U and Lenz-Plet, F and Barabasch, V and Albert, C and Schallenberg, A and Timm, C and Zacharias, N and Schmithausen, RM and Engelhart, S and Exner, M and Parcina, M and Schreiber, C and Bierbaum, G}, title = {Dissemination of multi-resistant Gram-negative bacteria into German wastewater and surface waters.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy057}, pmid = {29659796}, issn = {1574-6941}, abstract = {Carbapenem antibiotics constitute the mainstay therapy of nosocomial infections with extended spectrum beta-lactamase producing Gram-negative bacteria; however, resistance against these compounds is increasing. This study was designed to demonstrate that carbapenemase-producing bacteria are disseminated from hospitals into the environment. To this end, resistant bacteria were isolated from a clinical/urban and from a rural catchment system in Germany in 2016/17. The study followed the dissemination of resistant bacteria from the wastewater through the wastewater treatment plant (WWTP) into the receiving surface waters. The bacteria were cultivated on selective agar and characterized by antibiotic testing, real-time PCR targeting carbapenemase genes and typing. Bacteria with resistance to third generation cephalosporins were isolated from all sample sites. 134 isolates harboring carbapenemase genes encoding VIM, NDM and OXA-48 and 26 XDR (extensively drug-resistant) strains with susceptibility to only one or two antibiotics were isolated from the clinical/urban system. The rural system yielded eight carbapenemase producers and no XDR strains. In conclusion, clinical wastewaters were charged with a high proportion of multidrug resistant bacteria. Although most of these bacteria were eliminated during wastewater treatment, dissemination into surface waters is possible as single carbapenemase producers were still present in the effluent of the WWTP.}, } @article {pmid29659156, year = {2018}, author = {Gómez-Consarnau, L and Sachdeva, R and Gifford, SM and Cutter, LS and Fuhrman, JA and Sañudo-Wilhelmy, SA and Moran, MA}, title = {Mosaic patterns of B-vitamin synthesis and utilization in a natural marine microbial community.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2809-2823}, doi = {10.1111/1462-2920.14133}, pmid = {29659156}, issn = {1462-2920}, support = {253970//Marie Curie Actions-International Outgoing Fellowships/ ; OCE-1435666//US National Science Foundation/ ; OCE-1342694//US National Science Foundation/ ; }, abstract = {Aquatic environments contain large communities of microorganisms whose synergistic interactions mediate the cycling of major and trace nutrients, including vitamins. B-vitamins are essential coenzymes that many organisms cannot synthesize. Thus, their exchange among de novo synthesizers and auxotrophs is expected to play an important role in the microbial consortia and explain some of the temporal and spatial changes observed in diversity. In this study, we analyzed metatranscriptomes of a natural marine microbial community, diel sampled quarterly over one year to try to identify the potential major B-vitamin synthesizers and consumers. Transcriptomic data showed that the best-represented taxa dominated the expression of synthesis genes for some B-vitamins but lacked transcripts for others. For instance, Rhodobacterales dominated the expression of vitamin-B12 synthesis, but not of vitamin-B7 , whose synthesis transcripts were mainly represented by Flavobacteria. In contrast, bacterial groups that constituted less than 4% of the community (e.g., Verrucomicrobia) accounted for most of the vitamin-B1 synthesis transcripts. Furthermore, ambient vitamin-B1 concentrations were higher in samples collected during the day, and were positively correlated with chlorophyll-a concentrations. Our analysis supports the hypothesis that the mosaic of metabolic interdependencies through B-vitamin synthesis and exchange are key processes that contribute to shaping microbial communities in nature.}, } @article {pmid29659127, year = {2018}, author = {McLean-Inglis, AJL and Rallison, SP}, title = {Launching Environmental Microbiology: 'The most effective way to do it, is to do it'.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14132}, pmid = {29659127}, issn = {1462-2920}, } @article {pmid29658858, year = {2018}, author = {Wang, FQ and Ren, LH and Zou, RJ and Sun, YZ and Liu, XJ and Jiang, F and Liu, LJ}, title = {Carboxylicivirga sediminis sp. nov., isolated from coastal sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1896-1901}, doi = {10.1099/ijsem.0.002761}, pmid = {29658858}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A yellow-pigmented bacterial strain (JR1T) isolated from a sediment sample was subjected to a taxonomic study, based on phenotypic, genetic and physiological characterization. Here, we describe the cultivation and characteristics of strain JR1T, a novel member of the genus Carboxylicivirga in the family Marinilabiliaceae. Cells of strain JR1T were rod-shaped, Gram-stain-negative, non-motile and facultatively anaerobic. The temperature range for growth was 15-42 °C (optimum, 33 °C) and the pH range for growth was pH 6.0-8.5 (optimum, pH 7.0-7.5). Growth occurred in the presence of 0.0-10.0 % (w/v) NaCl (optimum 2.0-3.0 %). 16S rRNA gene sequence analysis produced results with 97.4 % similarity to Carboxylicivirga taeanensisMEBiC 08903T, 96.8 % similarity to Carboxylicivirga mesophilaMEBiC 07026T, 94.9 % similarity to Carboxylicivirga linearis FB218T and 94.6 % similarity to Carboxylicivirga flava Q15T. The DNA G+C content was 42.3 mol% and the major fatty acids were iso-C15 : 0, C15 : 0, anteiso-C15 : 0, C17 : 1ω6c and iso-C17 : 0-3OH. The major polar lipids detected were phosphatidylethanolamine and two unidentified lipids; the major respiratory quinone detected was MK-7. The results of the phenotypical, phylogenetic and biochemical analyses between the study strain and some related type strains indicated that this strain represent a novel species of the genus Carboxylicivirga within the family Marinilabiliaceae, for which the name Carboxylicivirga sediminis sp. nov. is proposed. The type strain is JR1T (=MCCC 1K03323T=KCTC 52869T).}, } @article {pmid29658162, year = {2018}, author = {Lacava, M and Camargo, A and Garcia, LF and Benamú, MA and Santana, M and Fang, J and Wang, X and Blamires, SJ}, title = {Web building and silk properties functionally covary among species of wolf spider.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {968-978}, doi = {10.1111/jeb.13278}, pmid = {29658162}, issn = {1420-9101}, abstract = {Although phylogenetic studies have shown covariation between the properties of spider major ampullate (MA) silk and web building, both spider webs and silks are highly plastic so we cannot be sure whether these traits functionally covary or just vary across environments that the spiders occupy. As MaSp2-like proteins provide MA silk with greater extensibility, their presence is considered necessary for spider webs to effectively capture prey. Wolf spiders (Lycosidae) are predominantly non-web building, but a select few species build webs. We accordingly collected MA silk from two web-building and six non-web-building species found in semirural ecosystems in Uruguay to test whether the presence of MaSp2-like proteins (indicated by amino acid composition, silk mechanical properties and silk nanostructures) was associated with web building across the group. The web-building and non-web-building species were from disparate subfamilies so we estimated a genetic phylogeny to perform appropriate comparisons. For all of the properties measured, we found differences between web-building and non-web-building species. A phylogenetic regression model confirmed that web building and not phylogenetic inertia influences silk properties. Our study definitively showed an ecological influence over spider silk properties. We expect that the presence of the MaSp2-like proteins and the subsequent nanostructures improves the mechanical performance of silks within the webs. Our study furthers our understanding of spider web and silk co-evolution and the ecological implications of spider silk properties.}, } @article {pmid29658161, year = {2018}, author = {Graham, BA and Heath, DD and Walter, RP and Mark, MM and Mennill, DJ}, title = {Parallel evolutionary forces influence the evolution of male and female songs in a tropical songbird.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {979-994}, doi = {10.1111/jeb.13279}, pmid = {29658161}, issn = {1420-9101}, abstract = {Given the important role that animal vocalizations play in mate attraction and resource defence, acoustic signals are expected to play a significant role in speciation. Most studies, however, have focused on the acoustic traits of male animals living in the temperate zone. In contrast to temperate environments, in the tropics, it is commonplace for both sexes to produce complex acoustic signals. Therefore, tropical birds offer the opportunity to compare the sexes and provide a more comprehensive understanding of the evolution of animal signals. In this study, we quantified patterns of acoustic variation in Rufous-and-white Wrens (Thryophilus rufalbus) from five populations in Central America. We quantified similarities and differences between male and female songs by comparing the role that acoustic adaptation, cultural isolation and neutral genetic divergence have played in shaping acoustic divergence. We found that males and females showed considerable acoustic variation across populations, although females exhibited greater population divergence than males. Redundancy analysis and partial-redundancy analysis revealed significant relationships between acoustic variation and ecological variables, genetic distance, and geographic distance. Both ambient background noise and geographic distance explained a high proportion of variance for both males and females, suggesting that both acoustic adaptation and cultural isolation influence song. Overall, our results indicate that parallel evolutionary forces act on male and female acoustic signals and highlight the important role that cultural drift and selection play in the evolution of both male and female songs.}, } @article {pmid29658159, year = {2018}, author = {Iglesias, PP and Soto, EM and Soto, IM and Colines, B and Hasson, E}, title = {The influence of developmental environment on courtship song in cactophilic Drosophila.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {957-967}, doi = {10.1111/jeb.13277}, pmid = {29658159}, issn = {1420-9101}, abstract = {Closely related species often differ in the signals involved in sexual communication and mate recognition. Determining the factors influencing signal quality (i.e. signal's content and conspicuousness) provides an important insight into the potential pathways by which these interspecific differences evolve. Host specificity could bias the direction of the evolution of sexual communication and the mate recognition system, favouring sensory channels that work best in the different host conditions. In this study, we focus on the cactophilic sibling species Drosophila buzzatii and D. koepferae that have diverged not only in the sensory channel used for sexual communication and mate recognition but also in the cactus species that use as primary hosts. We evaluate the role of the developmental environment in generating courtship song variation using an isofemale line design. Our results show that host environment during development induces changes in the courtship song of D. koepferae males, but not in D. buzzatii males. Moreover, we report for the first time that host rearing environment affects the conspicuousness of courtship song (i.e. song volume). Our results are mainly discussed in the context of the sensory drive hypothesis.}, } @article {pmid29657323, year = {2018}, author = {}, title = {A stomach virus's mysterious path into the gut is uncovered.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {277}, doi = {10.1038/d41586-018-04591-6}, pmid = {29657323}, issn = {1476-4687}, } @article {pmid29657322, year = {2018}, author = {}, title = {Laser-beam 'tweezers' guide two atoms to collide.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {276}, doi = {10.1038/d41586-018-04580-9}, pmid = {29657322}, issn = {1476-4687}, } @article {pmid29657321, year = {2018}, author = {}, title = {Deadly tumours are often born of childhood mutations.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {276-277}, doi = {10.1038/d41586-018-04442-4}, pmid = {29657321}, issn = {1476-4687}, } @article {pmid29657320, year = {2018}, author = {}, title = {Why fit fathers sire smarter offspring.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {276}, doi = {10.1038/d41586-018-04435-3}, pmid = {29657320}, issn = {1476-4687}, } @article {pmid29657319, year = {2018}, author = {}, title = {Speedy nanoengine zooms along DNA tracks.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {277}, doi = {10.1038/d41586-018-04437-1}, pmid = {29657319}, issn = {1476-4687}, } @article {pmid29657318, year = {2018}, author = {}, title = {Jays play nicely with the right hormone.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {277}, doi = {10.1038/d41586-018-04436-2}, pmid = {29657318}, issn = {1476-4687}, } @article {pmid29657317, year = {2018}, author = {}, title = {Gentle 'slow slip' earthquakes belie hidden danger.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {276}, doi = {10.1038/d41586-018-04258-2}, pmid = {29657317}, issn = {1476-4687}, } @article {pmid29657316, year = {2018}, author = {}, title = {Legless baby amphibians dine on mother's skin.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {277}, doi = {10.1038/d41586-018-04257-3}, pmid = {29657316}, issn = {1476-4687}, } @article {pmid29656929, year = {2018}, author = {McHenry, LJ and Stanistreet, IG}, title = {Tephrochronology of Bed II, Olduvai Gorge, Tanzania, and placement of the Oldowan-Acheulean transition.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {7-18}, doi = {10.1016/j.jhevol.2017.12.006}, pmid = {29656929}, issn = {1095-8606}, abstract = {Tuffaceous marker beds, derived from volcanic products from the Ngorongoro Volcanic Highlands, help define a stratigraphic framework for the world-renowned fossil and stone tool record exposed at Olduvai Gorge, Tanzania. However, previous efforts to constrain this tuff record, especially for Olduvai Bed II, have been limited because of erosion, contamination, reworking, and the alteration of volcanic glass under saline-alkaline conditions. This paper applies previously defined geochemical and mineralogical "fingerprints" for several major Bed II marker tuffs, based on glass (where available) and phenocrysts more resistant to alteration (feldspar, hornblende, augite, and titanomagnetite), to tuffs from stratigraphic sections in the Olduvai Junction Area, including previously and recently excavated Acheulean and Oldowan sites (HWK EE (Locality (Loc) 42), EF-HR (Loc 12a), FLK (Loc 45), and MNK (Loc 88)). The Middle Bed II Bird Print Tuff (BPT) is found to be more compositionally variable than previously reported but is still valuable as a stratigraphic marker over short distances. The confirmation of blocks of Tuff IID in conglomerate helps constrain Upper Bed II stratigraphy at sites where in-situ tuffs are absent. This paper also compiles the results of published geochronological research, providing stratigraphic context and updating previously reported dates using a consistent 40Ar/39Ar reference standard age. The results of this work support the following paleoanthropologically relevant conclusions: 1) the early Acheulean site EF-HR (Loc 12a) is situated above the level of Hay's Tuff IIC, and thus sits in Upper rather than Middle Bed II, (2) the HWK EE (Loc 42) Oldowan site is constrained between Tuff IIA and Tuff IIB, just above the boundary between Lower and Middle Bed II, and 3) the Acheulean site at FLK W most likely lies within the Middle Augitic Sandstone, above Tuff IIB, similar to the placements by Leakey and Hay for the earliest Acheulean at Olduvai.}, } @article {pmid29656535, year = {2018}, author = {Braz, HB and Almeida-Santos, SM and Murphy, CR and Thompson, MB}, title = {Uterine and eggshell modifications associated with the evolution of viviparity in South American water snakes (Helicops spp.).}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {3}, pages = {165-180}, doi = {10.1002/jez.b.22800}, pmid = {29656535}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Egg Shell/*physiology ; Embryo, Nonmammalian/physiology ; Female ; Snakes/classification/*physiology ; Uterus/*physiology ; Viviparity, Nonmammalian/*genetics/*physiology ; }, abstract = {The evolution of viviparity requires eggshell thinning to bring together the maternal uterus and extraembryonic membranes to form placentae for physiological exchanges. Eggshell thinning likely involves reduced activity of the uterine glands that secrete it. We tested these hypotheses by comparing the uterine and eggshell structure and histochemistry among oviparous and viviparous water snakes (Helicops) using phylogenetic methods. Eggshell thinning occurred convergently in all three origins of viviparity in Helicops and was accomplished by the loss of the mineral layer and thinning of the shell membrane. Uterine glands secrete the shell membrane in both oviparous and viviparous Helicops. These glands increase during vitellogenesis regardless of the reproductive mode, but they always reach smaller sizes in viviparous forms. As there is no phylogenetic signal in eggshell thickness and gland dimensions, we conclude that interspecific differences are related to reproductive mode and not phylogeny. Therefore, our results support the hypothesis that eggshell thinning is associated with the evolution of viviparity and that such thinning result from a reduction in gland size in viviparous taxa. Interestingly, the shell membrane thickness of viviparous females of the reproductively bimodal Helicops angulatus is intermediate between their oviparous and viviparous congeners. Thus, although eggshell thinning is required by the evolution of viviparity, a nearly complete loss of this structure is not. However, uterine gland dimensions are similar across viviparous Helicops. Fewer glands or their functional repurposing may explain the thinner shell membrane in viviparous species of Helicops in comparison to viviparous females of the bimodal H. angulatus.}, } @article {pmid29656105, year = {2018}, author = {Dias, C and Lima, KA and Araripe, J and Aleixo, A and Vallinoto, M and Sampaio, I and Schneider, H and Rêgo, PSD}, title = {Mitochondrial introgression obscures phylogenetic relationships among manakins of the genus Lepidothrix (Aves: Pipridae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {314-320}, doi = {10.1016/j.ympev.2018.04.017}, pmid = {29656105}, issn = {1095-9513}, mesh = {Animals ; DNA, Mitochondrial/genetics ; Haplotypes/genetics ; Mitochondria/*genetics ; Passeriformes/*classification/*genetics ; *Phylogeny ; }, abstract = {Lepidothrix is the most diverse genus of the family Pipridae, with eight recognized species. Although the genus' monophyly has been supported by both molecular and morphological characters, phylogenetic relationships and species limits within Lepidothrix remain uncertain. In the present study, we combined molecular sequences of mitochondrial (ND2 and COI) and nuclear (MYO, G3PDh and I5BF) markers in a multilocus analysis, to evaluate relationships and inter-specific limits among L. iris, L. nattereri, and L. vilasboasi, which are known to hybridize in eastern Amazonia. The results revealed a complex pattern, whereby events of secondary contact and gene flow after isolation and genetic and phenotypic differentiation prevented the recuperation of reciprocal monophyly among the studied taxa. The mitochondrial data indicate that L. nattereri is divided into two non-sister groups, one monophyletic, and the other, paraphyletic, with L. iris iris being more closely related to one of the two L. nattereri groups, while L. iris eucephala forms an undifferentiated clade with L. vilasboasi, probably resulting from an extensive process of mitochondrial introgression. In agreement with a previous study based on Single Nucleotide Polymorphism (SNP) data, mitochondrial haplotype networks also support that L. vilasboasi does not represent a recent "hybrid swarm" between L. iris and L. nattereri, but instead a genetically divergent lineage with a separate species status. Finally, the sister relationship recovered herein between L. iris iris and some western populations of L. nattereri currently in allopatry is also apparently explained by mitochondrial introgression, as also supported for nuclear genes by SNP data, indicating a complex scenario of past contact and gene flow between currently geographically distant Lepidothrix lineages.}, } @article {pmid29656104, year = {2018}, author = {Widhelm, TJ and Bertoletti, FR and Asztalos, MJ and Mercado-Díaz, JA and Huang, JP and Moncada, B and Lücking, R and Magain, N and Sérusiaux, E and Goffinet, B and Crouch, N and Mason-Gamer, R and Lumbsch, HT}, title = {Oligocene origin and drivers of diversification in the genus Sticta (Lobariaceae, Ascomycota).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {58-73}, doi = {10.1016/j.ympev.2018.04.006}, pmid = {29656104}, issn = {1095-9513}, mesh = {Ascomycota/*classification ; *Biodiversity ; Biological Evolution ; Extinction, Biological ; Lichens/classification ; *Phylogeny ; Phylogeography ; Time Factors ; }, abstract = {A major challenge to evolutionary biologists is to understand how biodiversity is distributed through space and time and across the tree of life. Diversification of organisms is influenced by many factors that act at different times and geographic locations but it is still not clear which have a significant impact and how drivers interact. To study diversification, we chose the lichen genus Sticta, by sampling through most of the global range and producing a time tree. We estimate that Sticta originated about 30 million years ago, but biogoegraphic analysis was unclear in estimating the origin of the genus. Furthermore, we investigated the effect of dispersal ability finding that Sticta has a high dispersal rate, as collections from Hawaii showed that divergent lineages colonized the islands at least four times. Symbiont interactions were investigated using BiSSE to understand if green-algal or cyanobacterial symbiont interactions influenced diversification, only to find that the positive results were driven almost completely by Type I error. On the other hand, another BiSSE analysis found that an association with Andean tectonic activity increases the speciation rate of species.}, } @article {pmid29656103, year = {2018}, author = {Godwin, RL and Opatova, V and Garrison, NL and Hamilton, CA and Bond, JE}, title = {Phylogeny of a cosmopolitan family of morphologically conserved trapdoor spiders (Mygalomorphae, Ctenizidae) using Anchored Hybrid Enrichment, with a description of the family, Halonoproctidae Pocock 1901.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {303-313}, doi = {10.1016/j.ympev.2018.04.008}, pmid = {29656103}, issn = {1095-9513}, mesh = {Animals ; Genome ; Likelihood Functions ; *Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Spiders/*classification/genetics ; }, abstract = {The mygalomorph family Ctenizidae has a world-wide distribution and currently contains nine genera and 135 species. However, the monophyly of this group has long been questioned on both morphological and molecular grounds. Here, we use Anchored Hybrid Enrichment (AHE) to gather hundreds of loci from across the genome for reconstructing the phylogenetic relationships among the nine genera and test the monophyly of the family. We also reconstruct the possible ancestral ranges of the most inclusive clade recovered. Using AHE, we generate a supermatrix of 565 loci and 115,209 bp for 27 individuals. For the first time, analyses using all nine genera produce results definitively establishing the non-monophyly of Ctenizidae. A lineage formed exclusively by representatives of South African Stasimopus was placed as the sister group to the remaining taxa in the tree, and the Mediterranean Cteniza and Cyrtocarenum were recovered with high support as sister to exemplars of Euctenizidae, Migidae, and Idiopidae. All the remaining genera-Bothriocyrtum, Conothele, Cyclocosmia, Hebestatis, Latouchia, and Ummidia-share a common ancestor. Based on these results, we formally elevate this clade to the level of family. Our results definitively establish both the non-monophyly of the Ctenizidae and non-validity of the subfamilies Ummidiinae and Ctenizinae. In order to establish the placement of the remaining three ctenizid genera, Cteniza, Cyrtocarenum, and Stasimopus, thorough analyses within the context of a complete mygalomorph phylogenetic framework are needed. We formally describe the family Halonoproctidae Pocock 1901 and infer that the family's most recent common ancestor was likely distributed in western North America and Asia.}, } @article {pmid29656089, year = {2018}, author = {Earl, LA and Falconieri, V and Subramaniam, S}, title = {Microbiology catches the cryo-EM bug.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {199-207}, pmid = {29656089}, issn = {1879-0364}, support = {ZIA BC010278-19//NULL/International ; ZIA BC010824-10//NULL/International ; ZIA BC010825-10//NULL/International ; }, mesh = {Antigen-Antibody Complex/ultrastructure ; Bacteria/ultrastructure ; Cryoelectron Microscopy/instrumentation/*methods ; Macromolecular Substances ; Membrane Proteins/ultrastructure ; Microbiological Techniques/*instrumentation/methods ; Nanoparticles/ultrastructure ; Viruses/ultrastructure ; }, abstract = {Over the past few years, the advances in technology and methods that have revolutionized cryo-EM are allowing for key insights in a variety of areas in biology, and microbiology is no exception. A wide range of important macromolecular assemblies in prokaryotic and eukaryotic cells, as well as intact viruses, have now become accessible to investigation by new methods in 3D electron microscopy. We focus here on selected examples that illustrate this breadth, and review the application of methods in single particle cryo-EM and cryo-electron tomography to progress in the structural biology of CRISPR systems, visualization of small molecule drugs in membrane proteins, in situ visualization of bacterial nanomachines, and the analysis of antigen-antibody interactions to drive vaccine design.}, } @article {pmid29656009, year = {2018}, author = {Palazzotto, E and Weber, T}, title = {Omics and multi-omics approaches to study the biosynthesis of secondary metabolites in microorganisms.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {109-116}, doi = {10.1016/j.mib.2018.03.004}, pmid = {29656009}, issn = {1879-0364}, abstract = {Natural products produced by microorganisms represent the main source of bioactive molecules. The development of high-throughput (omics) techniques have importantly contributed to the renaissance of new antibiotic discovery increasing our understanding of complex mechanisms controlling the expression of biosynthetic gene clusters (BGCs) encoding secondary metabolites. In this context this review highlights recent progress in the use and integration of 'omics' approaches with focuses on genomics, transcriptomics, proteomics metabolomics meta-omics and combined omics as powerful strategy to discover new antibiotics.}, } @article {pmid29655858, year = {2018}, author = {White, TE}, title = {Illuminating the Evolution of Iridescence.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {6}, pages = {374-375}, doi = {10.1016/j.tree.2018.03.011}, pmid = {29655858}, issn = {1872-8383}, mesh = {*Iridescence ; Lighting ; *Memory ; }, abstract = {Iridescence, a change in hue with viewing or illumination geometry, is a common feature of colour patterns in nature, though its significance remains elusive. Recent studies of floral iridescence reveal its functional versatility in enhancing the detection and discrimination of resources by insect viewers, as well as augmenting higher-level processes of memory and perception. Coupled with a known evolutionary lability, these results suggest intriguing possibilities for how this optical curiosity may act as a key to diversification.}, } @article {pmid29655519, year = {2018}, author = {Hardesty, RA}, title = {Much ado about mice: Standard-setting in model organism research.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {68-69}, number = {}, pages = {15-24}, doi = {10.1016/j.shpsc.2018.04.001}, pmid = {29655519}, issn = {1879-2499}, mesh = {Animals ; Anthropology, Cultural/methods ; *Cognition ; *Disease Models, Animal ; Down Syndrome/*psychology ; Humans ; Knowledge ; *Mice ; Neurosciences/*standards ; Research/standards ; }, abstract = {Recently there has been a practice turn in the philosophy of science that has called for analyses to be grounded in the actual doings of everyday science. This paper is in furtherance of this call and it does so by employing participant-observation ethnographic methods as a tool for discovering epistemological features of scientific practice in a neuroscience lab. The case I present focuses on a group of neurobiologists researching the genetic underpinnings of cognition in Down syndrome (DS) and how they have developed a new mouse model which they argue should be regarded as the "gold standard" for all DS mouse research. Through use of ethnographic methods, interviews, and analyses of publications, I uncover how the lab constructed their new mouse model. Additionally, I describe how model organisms can serve as abstract standards for scientific work that impact the epistemic value of scientific claims, regulate practice, and constrain future work.}, } @article {pmid29655370, year = {2018}, author = {Torner, N and Martínez, A and Basile, L and Mosquera, M and Antón, A and Rius, C and Sala, MR and Minguell, S and Plasencia, E and Carol, M and Godoy, P and Follia, N and Barrabeig, I and Marcos, MA and Pumarola, T and Jané, M}, title = {Descriptive study of severe hospitalized cases of laboratory-confirmed influenza during five epidemic seasons (2010-2015).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {244}, pmid = {29655370}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Antiviral Agents/*therapeutic use ; Child ; Child, Preschool ; Epidemics/*statistics & numerical data ; Female ; Hospitalization/*statistics & numerical data ; Humans ; Infant ; Influenza A Virus, H1N1 Subtype/*isolation & purification ; Influenza A Virus, H3N2 Subtype/*isolation & purification ; Influenza, Human/drug therapy/*epidemiology/mortality/*virology ; Male ; Middle Aged ; *Sentinel Surveillance ; Spain/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: The Plan of Information on Acute Respiratory Infections in Catalonia (PIDIRAC) included the surveillance of severe hospitalized cases of laboratory-confirmed influenza (SHCLCI) in 2009. The objective of this study was to determine the clinical, epidemiological and virological features of SHCLCI recorded in 12 sentinel hospitals during five influenza seasons.

RESULTS: From a sample of SHCLCI recorded during the 5 influenza epidemics seasons from 2010-2011 to 2014-2015, Cases were confirmed by PCR and/or viral isolation in cell cultures from respiratory samples. A total of 1400 SHCLCI were recorded, 33% required ICU admission and 12% died. The median age of cases was 61 years (range 0-101 years); 70.5% were unvaccinated; 80.4% received antiviral treatment (in 79.6 and 24% of cases within 48 h after hospital admission and the onset of symptoms, respectively); influenza virus A [37.9% A (H1N1)pdm09, 29.3% A (H3N2)] was identified in 87.7% of cases. Surveillance of SHCLCI provides an estimate of the severity of seasonal influenza epidemics and the identification and characterization of at-risk groups in order to facilitate preventive measures such as vaccination and early antiviral treatment.}, } @article {pmid29654746, year = {2018}, author = {Ward, L and Pang, ASW and Evans, SE and Stern, CD}, title = {The role of the notochord in amniote vertebral column segmentation.}, journal = {Developmental biology}, volume = {439}, number = {1}, pages = {3-18}, pmid = {29654746}, issn = {1095-564X}, support = {R01 GM076692/GM/NIGMS NIH HHS/United States ; R01 GM076690/GM/NIGMS NIH HHS/United States ; 1052629//Biotechnology and Biological Sciences Research Council/United Kingdom ; G0700095//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Body Patterning/physiology ; Cell Differentiation ; Chick Embryo ; Chickens ; Intervertebral Disc/embryology/physiology ; Notochord/embryology/*physiology ; Somites/embryology/*physiology ; Spine/embryology/metabolism/*physiology ; }, abstract = {The vertebral column is segmented, comprising an alternating series of vertebrae and intervertebral discs along the head-tail axis. The vertebrae and outer portion (annulus fibrosus) of the disc are derived from the sclerotome part of the somites, whereas the inner nucleus pulposus of the disc is derived from the notochord. Here we investigate the role of the notochord in vertebral patterning through a series of microsurgical experiments in chick embryos. Ablation of the notochord causes loss of segmentation of vertebral bodies and discs. However, the notochord cannot segment in the absence of the surrounding sclerotome. To test whether the notochord dictates sclerotome segmentation, we grafted an ectopic notochord. We find that the intrinsic segmentation of the sclerotome is dominant over any segmental information the notochord may possess, and no evidence that the chick notochord is intrinsically segmented. We propose that the segmental pattern of vertebral bodies and discs in chick is dictated by the sclerotome, which first signals to the notochord to ensure that the nucleus pulposus develops in register with the somite-derived annulus fibrosus. Later, the notochord is required for maintenance of sclerotome segmentation as the mature vertebral bodies and intervertebral discs form. These results highlight differences in vertebral development between amniotes and teleosts including zebrafish, where the notochord dictates the segmental pattern. The relative importance of the sclerotome and notochord in vertebral patterning has changed significantly during evolution.}, } @article {pmid29654745, year = {2018}, author = {Hu, J and Shi, Y and Xia, M and Liu, Z and Zhang, R and Luo, H and Zhang, T and Yang, Z and Yuan, B}, title = {WDR1-regulated actin dynamics is required for outflow tract and right ventricle development.}, journal = {Developmental biology}, volume = {438}, number = {2}, pages = {124-137}, doi = {10.1016/j.ydbio.2018.04.004}, pmid = {29654745}, issn = {1095-564X}, mesh = {Actins/genetics/metabolism ; Animals ; Embryo, Mammalian/embryology ; Embryonic Development/genetics/physiology ; Gene Expression Regulation, Developmental/genetics ; Heart/embryology ; Heart Defects, Congenital/genetics ; Heart Ventricles/*embryology ; Mice ; Mice, Knockout ; Microfilament Proteins/genetics/metabolism/*physiology ; Myocardium ; Myocytes, Cardiac ; Organogenesis ; Signal Transduction ; Ventricular Outflow Obstruction ; }, abstract = {Outflow tract (OFT) anomalies account for about 30% of human congenital heart defects detected at birth. The second heart field (SHF) progenitors contribute to OFT and right ventricle (RV) development, but the process largely remains unknown. WDR1 (WD-repeat domain 1) is a major co-factor of actin depolymerizing factor (ADF)/cofilin that actively disassembles ADF/cofilin-bound actin filaments. Its function in embryonic heart development has been unknown. Using Wdr1 floxed mice and Nkx2.5-Cre, we deleted Wdr1 in embryonic heart (Wdr1F/F;Nkx2.5-Cre) and found that these mice exhibited embryonic lethality, and hypoplasia of OFT and RV. To investigate the role of WDR1 in OFT and RV development, we generated SHF progenitors-specific Wdr1 deletion mice (shfKO). shfKO mice began to die at embryonic day 11.5 (E11.5), and displayed decreased size of the proximal OFT and RV at E10.5. In shfKO embryos, neither the number of SHF cells deployment to OFT nor cell proliferation and the cell number were changed, whereas the cellular organization and myofibrillar assembly of cardiomyocytes were severely disrupted. In the proximal OFT and RV of both shfKO and Wdr1F/F;Nkx2.5-Cre embryos, cardiomyocytes were dissociated from the outer compact myocardial layer and loosely and disorderly arranged into multilayered myocardium. Our results demonstrate that WDR1 is indispensable for normal OFT and RV development, and suggest that WDR1-mediated actin dynamics functions in controlling the size of OFT and RV, which might through regulating the spatial arrangement of cardiomyocytes.}, } @article {pmid29654714, year = {2018}, author = {Aucamp, J and Bronkhorst, AJ and Badenhorst, CPS and Pretorius, PJ}, title = {The diverse origins of circulating cell-free DNA in the human body: a critical re-evaluation of the literature.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1649-1683}, doi = {10.1111/brv.12413}, pmid = {29654714}, issn = {1469-185X}, abstract = {Since the detection of cell-free DNA (cfDNA) in human plasma in 1948, it has been investigated as a non-invasive screening tool for many diseases, especially solid tumours and foetal genetic abnormalities. However, to date our lack of knowledge regarding the origin and purpose of cfDNA in a physiological environment has limited its use to more obvious diagnostics, neglecting, for example, its potential utility in the identification of predisposition to disease, earlier detection of cancers, and lifestyle-induced epigenetic changes. Moreover, the concept or mechanism of cfDNA could also have potential therapeutic uses such as in immuno- or gene therapy. This review presents an extensive compilation of the putative origins of cfDNA and then contrasts the contributions of cellular breakdown processes with active mechanisms for the release of cfDNA into the extracellular environment. The involvement of cfDNA derived from both cellular breakdown and active release in lateral information transfer is also discussed. We hope to encourage researchers to adopt a more holistic view of cfDNA research, taking into account all the biological pathways in which cfDNA is involved, and to give serious consideration to the integration of in vitro and in vivo research. We also wish to encourage researchers not to limit their focus to the apoptotic or necrotic fraction of cfDNA, but to investigate the intercellular messaging capabilities of the actively released fraction of cfDNA and to study the role of cfDNA in pathogenesis.}, } @article {pmid29654293, year = {2018}, author = {Sydnes, LK}, title = {How to curb production of chemical weapons.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {293-295}, doi = {10.1038/d41586-018-04579-2}, pmid = {29654293}, issn = {1476-4687}, mesh = {Chemical Industry/ethics/legislation & jurisprudence ; Chemical Safety/*legislation & jurisprudence/standards ; Chemical Warfare/*legislation & jurisprudence/*prevention & control ; Chemical Warfare Agents/*legislation & jurisprudence/poisoning/*supply & distribution/toxicity ; Chlorine/poisoning/toxicity ; Forensic Toxicology ; Humans ; Mustard Compounds/poisoning/toxicity ; Nerve Agents/poisoning/toxicity ; Organophosphates/toxicity ; Organothiophosphorus Compounds/poisoning ; Syria ; }, } @article {pmid29654148, year = {2018}, author = {Anchang, B and Davis, KL and Fienberg, HG and Williamson, BD and Bendall, SC and Karacosta, LG and Tibshirani, R and Nolan, GP and Plevritis, SK}, title = {DRUG-NEM: Optimizing drug combinations using single-cell perturbation response to account for intratumoral heterogeneity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4294-E4303}, pmid = {29654148}, issn = {1091-6490}, support = {T32 AI007290/AI/NIAID NIH HHS/United States ; R25 CA180993/CA/NCI NIH HHS/United States ; U19 AI100627/AI/NIAID NIH HHS/United States ; U54 CA209971/CA/NCI NIH HHS/United States ; U54 CA149145/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Combined Chemotherapy Protocols/*pharmacokinetics/*pharmacology ; Biomarkers, Tumor/*metabolism ; *Computer Simulation ; HeLa Cells ; Humans ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/*metabolism ; }, abstract = {An individual malignant tumor is composed of a heterogeneous collection of single cells with distinct molecular and phenotypic features, a phenomenon termed intratumoral heterogeneity. Intratumoral heterogeneity poses challenges for cancer treatment, motivating the need for combination therapies. Single-cell technologies are now available to guide effective drug combinations by accounting for intratumoral heterogeneity through the analysis of the signaling perturbations of an individual tumor sample screened by a drug panel. In particular, Mass Cytometry Time-of-Flight (CyTOF) is a high-throughput single-cell technology that enables the simultaneous measurements of multiple ([Formula: see text]40) intracellular and surface markers at the level of single cells for hundreds of thousands of cells in a sample. We developed a computational framework, entitled Drug Nested Effects Models (DRUG-NEM), to analyze CyTOF single-drug perturbation data for the purpose of individualizing drug combinations. DRUG-NEM optimizes drug combinations by choosing the minimum number of drugs that produce the maximal desired intracellular effects based on nested effects modeling. We demonstrate the performance of DRUG-NEM using single-cell drug perturbation data from tumor cell lines and primary leukemia samples.}, } @article {pmid29654147, year = {2018}, author = {Xu, G and Wang, Z and Ling, R and Zhou, J and Chen, XD and Holm, RH}, title = {Ligand metathesis as rational strategy for the synthesis of cubane-type heteroleptic iron-sulfur clusters relevant to the FeMo cofactor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {5089-5092}, pmid = {29654147}, issn = {1091-6490}, mesh = {Catalysis ; Catalytic Domain ; Coordination Complexes/*chemistry ; Crystallography, X-Ray ; Iron-Sulfur Proteins/chemistry/metabolism ; Ligands ; Models, Molecular ; Molecular Structure ; Molybdenum/*chemistry ; Molybdoferredoxin/*chemistry ; Nitrogenase/chemistry/metabolism ; Oxidation-Reduction ; Sulfur/*chemistry ; }, abstract = {Molybdenum-dependent nitrogenases catalyze the transformation of dinitrogen into ammonia under ambient conditions. The active site (FeMo cofactor) is the structurally and electronically complex weak-field metal cluster [MoFe7S9C] built of Fe4S3 and MoFe3S3C portions connected by three sulfur bridges and containing an interstitial carbon atom centered in an Fe6 trigonal prism. Chemical synthesis of this cluster is a major challenge in biomimetic inorganic chemistry. One synthetic approach of core ligand metathesis has been developed based on the design and synthesis of unprecedented incomplete ([(Tp*)WFe2S3Q3]-) and complete ([(Tp*)WFe3S3Q4]2-) cubane-type clusters containing bridging halide (Q = halide). These clusters are achieved by template-assisted assembly in the presence of sodium benzophenone ketyl reductant; products are controlled by reaction stoichiometry. Incomplete cubane clusters are subject to a variety of metathesis reactions resulting in substitution of a μ2-bridging ligand with other bridges such as N3-, MeO-, and EtS- Reactions of complete cubanes with Me3SiN3 and S8 undergo a redox metathesis process and lead to core ligand displacement and formation of [(Tp*)WFe3S3(μ3-Q)Cl3]- (Q = Me3SiN2-, S2-). This work affords entry to a wide variety of heteroleptic clusters derivable from incomplete and complete cubanes; examples are provided. Among these is the cluster [(Tp*)WFe3S3(μ3-NSiMe3)Cl3]-, one of the very few instances of a synthetic Fe-S cluster containing a light atom (C, N, O) in the core, which constitutes a close mimic of the [MoFe3S3C] fragment in FeMo cofactor. Superposition of them and comparison of metric information disclose a clear structural relationship [Tp* = tris(3,5-dimethyl-1-pyrazolyl)hydroborate(1-)].}, } @article {pmid29654146, year = {2018}, author = {Ahn, E and Araki, K and Hashimoto, M and Li, W and Riley, JL and Cheung, J and Sharpe, AH and Freeman, GJ and Irving, BA and Ahmed, R}, title = {Role of PD-1 during effector CD8 T cell differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4749-4754}, pmid = {29654146}, issn = {1091-6490}, support = {P01 AI056299/AI/NIAID NIH HHS/United States ; R01 AI030048/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Cell Differentiation/genetics/*immunology ; Female ; *Lymphocyte Activation ; Lymphocytic Choriomeningitis/genetics/*immunology ; Lymphocytic choriomeningitis virus/*immunology ; Mice ; Programmed Cell Death 1 Receptor/genetics/*immunology ; Receptors, Antigen, T-Cell/genetics/immunology ; }, abstract = {PD-1 (programmed cell death-1) is the central inhibitory receptor regulating CD8 T cell exhaustion during chronic viral infection and cancer. Interestingly, PD-1 is also expressed transiently by activated CD8 T cells during acute viral infection, but the role of PD-1 in modulating T cell effector differentiation and function is not well defined. To address this question, we examined the expression kinetics and role of PD-1 during acute lymphocytic choriomeningitis virus (LCMV) infection of mice. PD-1 was rapidly up-regulated in vivo upon activation of naive virus-specific CD8 T cells within 24 h after LCMV infection and in less than 4 h after peptide injection, well before any cell division had occurred. This rapid PD-1 expression by CD8 T cells was driven predominantly by antigen receptor signaling since infection with a LCMV strain with a mutation in the CD8 T cell epitope did not result in the increase of PD-1 on antigen-specific CD8 T cells. Blockade of the PD-1 pathway using anti-PD-L1 or anti-PD-1 antibodies during the early phase of acute LCMV infection increased mTOR signaling and granzyme B expression in virus-specific CD8 T cells and resulted in faster clearance of the infection. These results show that PD-1 plays an inhibitory role during the naive-to-effector CD8 T cell transition and that the PD-1 pathway can also be modulated at this stage of T cell differentiation. These findings have implications for developing therapeutic vaccination strategies in combination with PD-1 blockade.}, } @article {pmid29654145, year = {2018}, author = {Tsai, YL and Ha, DP and Zhao, H and Carlos, AJ and Wei, S and Pun, TK and Wu, K and Zandi, E and Kelly, K and Lee, AS}, title = {Endoplasmic reticulum stress activates SRC, relocating chaperones to the cell surface where GRP78/CD109 blocks TGF-β signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4245-E4254}, pmid = {29654145}, issn = {1091-6490}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; P30 DK048522/DK/NIDDK NIH HHS/United States ; R01 CA027607/CA/NCI NIH HHS/United States ; }, mesh = {ADP-Ribosylation Factor 1/genetics/metabolism ; Adaptor Proteins, Signal Transducing/genetics/metabolism ; Antigens, CD/genetics/*metabolism ; Endoplasmic Reticulum Stress/*physiology ; Enzyme Activation/physiology ; GPI-Linked Proteins/genetics/metabolism ; HEK293 Cells ; HeLa Cells ; Heat-Shock Proteins/genetics/*metabolism ; Humans ; MCF-7 Cells ; Neoplasm Proteins/genetics/*metabolism ; Protein Transport/physiology ; Signal Transduction/*physiology ; Smad2 Protein/genetics/metabolism ; Transforming Growth Factor beta/genetics/*metabolism ; src-Family Kinases/*metabolism ; }, abstract = {The discovery that endoplasmic reticulum (ER) luminal chaperones such as GRP78/BiP can escape to the cell surface upon ER stress where they regulate cell signaling, proliferation, apoptosis, and immunity represents a paradigm shift. Toward deciphering the mechanisms, we report here that, upon ER stress, IRE1α binds to and triggers tyrosine kinase SRC activation, leading to ASAP1 phosphorylation and Golgi accumulation of ASAP1 and Arf1-GTP, resulting in KDEL receptor dispersion from the Golgi and suppression of retrograde transport. At the cell surface, GRP78 binds to and acts in concert with a glycosylphosphatidylinositol-anchored protein, CD109, in blocking TGF-β signaling by promoting the routing of the TGF-β receptor to the caveolae, thereby disrupting its binding to and activation of Smad2. Collectively, we uncover a SRC-mediated signaling cascade that leads to the relocalization of ER chaperones to the cell surface and a mechanism whereby GRP78 counteracts the tumor-suppressor effect of TGF-β.}, } @article {pmid29654144, year = {2018}, author = {Mortensen, SA and Sander, B and Jensen, RK and Pedersen, JS and Golas, MM and Thiel, S and Andersen, GR}, title = {Models of the complement C1 complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3866}, pmid = {29654144}, issn = {1091-6490}, mesh = {Complement Activation ; Complement C1 ; Complement C1q ; *Complement C1r ; *Complement C1s ; }, } @article {pmid29654143, year = {2018}, author = {Almitairi, JOM and Venkatraman Girija, U and Furze, CM and Simpson-Gray, X and Badakshi, F and Marshall, JE and Schwaeble, WJ and Mitchell, DA and Moody, PCE and Wallis, R}, title = {Reply to Mortensen et al.: The zymogen form of complement component C1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3867-E3868}, pmid = {29654143}, issn = {1091-6490}, mesh = {Complement Activation ; *Complement C1 ; Complement C1q ; *Complement C1r ; Complement C1s ; Enzyme Precursors ; }, } @article {pmid29653763, year = {2018}, author = {Brooks, DS and Eronen, MI}, title = {The significance of levels of organization for scientific research: A heuristic approach.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {68-69}, number = {}, pages = {34-41}, doi = {10.1016/j.shpsc.2018.04.003}, pmid = {29653763}, issn = {1879-2499}, mesh = {Biology/*organization & administration ; *Heuristics ; Philosophy ; Research/*organization & administration ; }, abstract = {The concept of 'levels of organization' has come under fire recently as being useless for scientific and philosophical purposes. In this paper, we show that 'levels' is actually a remarkably resilient and constructive conceptual tool that can be, and in fact is, used for a variety of purposes. To this effect, we articulate an account of the importance of the levels concept seen in light of its status as a major organizing concept of biology. We argue that the usefulness of 'levels' is best seen in the heuristic contributions the concept makes to treating and structuring scientific problems. We illustrate this with two examples from biological research.}, } @article {pmid29653594, year = {2018}, author = {Hammer, SE and Tautscher, B and Pucher, E and Kowarik, K and Reschreiter, H and Kern, A and Haring, E}, title = {Bronze Age meat industry: ancient mitochondrial DNA analyses of pig bones from the prehistoric salt mines of Hallstatt (Austria).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {243}, pmid = {29653594}, issn = {1756-0500}, mesh = {Animals ; Austria ; DNA, Ancient/*analysis ; DNA, Mitochondrial/*analysis ; Mining ; Pilot Projects ; Sequence Analysis, DNA/*methods ; *Sodium Chloride ; Sus scrofa/*genetics ; }, abstract = {OBJECTIVE: In the Bronze Age Hallstatt metropolis ('Salzkammergut' region, Upper Austria), salt richness enabled the preservation of pork meat to sustain people's livelihood suggesting an organized meat production industry on a yearly basis of hundreds of pigs. To pattern the geographic and temporal framework of the early management of pig populations in the surrounding areas of Hallstatt, we want to gain insights into the phylogeographic network based on DNA sequence variation among modern pigs, wild boars and prehistoric (likely) domestic pigs.

RESULTS: In this pilot study, we successfully adapted ancient DNA extraction and sequencing approaches for the analysis of mitochondrial DNA sequence variation in ten prehistoric porcine teeth specimens. Minimum-spanning network analyses revealed unique mitochondrial control region DNA haplotypes ranging within the variation of modern domestic pig and wild boar lineages and even shared haplotypes between prehistoric and modern domestic pigs and wild boars were observed.}, } @article {pmid29653534, year = {2018}, author = {Delsuc, F and Philippe, H and Tsagkogeorga, G and Simion, P and Tilak, MK and Turon, X and López-Legentil, S and Piette, J and Lemaire, P and Douzery, EJP}, title = {A phylogenomic framework and timescale for comparative studies of tunicates.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {39}, pmid = {29653534}, issn = {1741-7007}, abstract = {BACKGROUND: Tunicates are the closest relatives of vertebrates and are widely used as models to study the evolutionary developmental biology of chordates. Their phylogeny, however, remains poorly understood, and to date, only the 18S rRNA nuclear gene and mitogenomes have been used to delineate the major groups of tunicates. To resolve their evolutionary relationships and provide a first estimate of their divergence times, we used a transcriptomic approach to build a phylogenomic dataset including all major tunicate lineages, consisting of 258 evolutionarily conserved orthologous genes from representative species.

RESULTS: Phylogenetic analyses using site-heterogeneous CAT mixture models of amino acid sequence evolution resulted in a strongly supported tree topology resolving the relationships among four major tunicate clades: (1) Appendicularia, (2) Thaliacea + Phlebobranchia + Aplousobranchia, (3) Molgulidae, and (4) Styelidae + Pyuridae. Notably, the morphologically derived Thaliacea are confirmed as the sister group of the clade uniting Phlebobranchia + Aplousobranchia within which the precise position of the model ascidian genus Ciona remains uncertain. Relaxed molecular clock analyses accommodating the accelerated evolutionary rate of tunicates reveal ancient diversification (~ 450-350 million years ago) among the major groups and allow one to compare their evolutionary age with respect to the major vertebrate model lineages.

CONCLUSIONS: Our study represents the most comprehensive phylogenomic dataset for the main tunicate lineages. It offers a reference phylogenetic framework and first tentative timescale for tunicates, allowing a direct comparison with vertebrate model species in comparative genomics and evolutionary developmental biology studies.}, } @article {pmid29653520, year = {2018}, author = {Olohan, L and Gardiner, LJ and Lucaci, A and Steuernagel, B and Wulff, B and Kenny, J and Hall, N and Hall, A}, title = {A modified sequence capture approach allowing standard and methylation analyses of the same enriched genomic DNA sample.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {250}, pmid = {29653520}, issn = {1471-2164}, support = {BB/N005104/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L011786/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*DNA Methylation ; Genome, Chloroplast ; *Genome, Plant ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA/*methods/standards ; Triticum/*genetics ; }, abstract = {BACKGROUND: Bread wheat has a large complex genome that makes whole genome resequencing costly. Therefore, genome complexity reduction techniques such as sequence capture make re-sequencing cost effective. With a high-quality draft wheat genome now available it is possible to design capture probe sets and to use them to accurately genotype and anchor SNPs to the genome. Furthermore, in addition to genetic variation, epigenetic variation provides a source of natural variation contributing to changes in gene expression and phenotype that can be profiled at the base pair level using sequence capture coupled with bisulphite treatment. Here, we present a new 12 Mbp wheat capture probe set, that allows both the profiling of genotype and methylation from the same DNA sample. Furthermore, we present a method, based on Agilent SureSelect Methyl-Seq, that will use a single capture assay as a starting point to allow both DNA sequencing and methyl-seq.

RESULTS: Our method uses a single capture assay that is sequentially split and used for both DNA sequencing and methyl-seq. The resultant genotype and epi-type data is highly comparable in terms of coverage and SNP/methylation site identification to that generated from separate captures for DNA sequencing and methyl-seq. Furthermore, by defining SNP frequencies in a diverse landrace from the Watkins collection we highlight the importance of having genotype data to prevent false positive methylation calls. Finally, we present the design of a new 12 Mbp wheat capture and demonstrate its successful application to re-sequence wheat.

CONCLUSIONS: We present a cost-effective method for performing both DNA sequencing and methyl-seq from a single capture reaction thus reducing reagent costs, sample preparation time and DNA requirements for these complementary analyses.}, } @article {pmid29653518, year = {2018}, author = {Modrák, M and Vohradský, J}, title = {Genexpi: a toolset for identifying regulons and validating gene regulatory networks using time-course expression data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {137}, pmid = {29653518}, issn = {1471-2105}, support = {LM20150055//Ministerstvo Školství, Mládeže a Tělovýchovy/International ; }, mesh = {Bacteria/genetics ; *Databases, Genetic ; Eukaryota/genetics ; *Gene Expression Regulation ; *Gene Regulatory Networks ; Humans ; Regulon/*genetics ; Reproducibility of Results ; Saccharomyces cerevisiae/genetics ; *Software ; Time Factors ; }, abstract = {BACKGROUND: Identifying regulons of sigma factors is a vital subtask of gene network inference. Integrating multiple sources of data is essential for correct identification of regulons and complete gene regulatory networks. Time series of expression data measured with microarrays or RNA-seq combined with static binding experiments (e.g., ChIP-seq) or literature mining may be used for inference of sigma factor regulatory networks.

RESULTS: We introduce Genexpi: a tool to identify sigma factors by combining candidates obtained from ChIP experiments or literature mining with time-course gene expression data. While Genexpi can be used to infer other types of regulatory interactions, it was designed and validated on real biological data from bacterial regulons. In this paper, we put primary focus on CyGenexpi: a plugin integrating Genexpi with the Cytoscape software for ease of use. As a part of this effort, a plugin for handling time series data in Cytoscape called CyDataseries has been developed and made available. Genexpi is also available as a standalone command line tool and an R package.

CONCLUSIONS: Genexpi is a useful part of gene network inference toolbox. It provides meaningful information about the composition of regulons and delivers biologically interpretable results.}, } @article {pmid29653514, year = {2018}, author = {Zhang, N and Yang, L and Luo, S and Wang, X and Wang, W and Cheng, Y and Tian, H and Zheng, K and Cai, L and Wang, S}, title = {Genetic evidence suggests that GIS functions downstream of TCL1 to regulate trichome formation in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {63}, pmid = {29653514}, issn = {1471-2229}, support = {2016YFD0101902//Ministry of Science and Technology of the People's Republic of China/ ; }, mesh = {Arabidopsis/*genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; *Geographic Information Systems ; Transcription Factors/genetics/metabolism ; Trichomes/*genetics/*growth & development/metabolism ; }, abstract = {BACKGROUND: Trichome formation in Arabidopsis is regulated by a MBW complex formed by MYB, bHLH and WD40 transcriptional factors, which can activate GLABRA2 (GL2) and the R3 MYB transcription factor genes. GL2 promotes trichome formation, whereas R3 MYBs are able to block the formation of the MBW complex. It has been reported that the C2H2 transcription factor GIS (GLABROUS INFLORESCENCE STEMS) functions upstream of the MBW activator complex to regulate trichome formation, and that the expression of TCL1 is not regulated by the MBW complex. However, gis and the R3 MYB gene mutant tcl1 (trichomeless 1) have opposite inflorescence trichome phenotypes, but their relationship in regulating trichome formation remained unknown.

RESULTS: By generating and characterization of the gis tcl1 double mutant, we found that trichome formation in the gis tcl1double and the tcl1 single mutants were largely indistinguishable, but the trichome formation in the 35S:TCL1/gis transgenic plant was similar to that in the gis mutant. By using quantitative RT-PCR analysis, we showed that expression level of GIS was increased in the triple mutant tcl1 try cpc, but the expression level of TCL1 was not affected in the gis mutant. On the other hand, trichome morphology in both gis tcl1 and 35S:TCL1/gis plants was similar to that in the gis mutant.

CONCLUSIONS: In summary, our results indicate that GIS may work downstream of TCL1 to regulate trichome formation, and GIS has a dominant role in controlling trichome morphology.}, } @article {pmid29653512, year = {2018}, author = {Gao, D and Kong, F and Sun, P and Bi, G and Mao, Y}, title = {Transcriptome-wide identification of optimal reference genes for expression analysis of Pyropia yezoensis responses to abiotic stress.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {251}, pmid = {29653512}, issn = {1471-2164}, support = {31372517, 31672641//National Natural Science Foundation of China/ ; 2015ASKJ02//Scientific and Technological Innovation Project Financially Supported by Qingdao National Laboratory for Marine Science and Technology/ ; 2016DKA30470//Project of National Infrastructure of Fishery Germplasm Resources/ ; 201762016, 201562018, 201564009//Fundamental Research Funds for the Central Universities/ ; }, mesh = {*Gene Expression Profiling ; Genes, Plant ; Real-Time Polymerase Chain Reaction/*standards ; Reference Standards ; Rhodophyta/*genetics/metabolism ; Stress, Physiological/*genetics ; }, abstract = {BACKGROUND: Pyropia yezoensis, a marine red alga, is an ideal research model for studying the mechanisms of abiotic stress tolerance in intertidal seaweed. Real-time quantitative polymerase chain reaction (RT-qPCR) is the most commonly used method to analyze gene expression levels. To accurately quantify gene expression, selection and validation of stable reference genes is required.

RESULTS: We used transcriptome profiling data from different abiotic stress treatments to identify six genes with relatively stable expression levels: MAP, ATPase, CGS1, PPK, DPE2, and FHP. These six genes and three conventional reference genes, UBC, EF1-α, and eif4A, were chosen as candidates for optimal reference gene selection. Five common statistical approaches (geNorm, ΔCt method, NormFinder, BestKeeper, and ReFinder) were used to identify the stability of each reference gene. Our results show that: MAP, UBC, and FHP are stably expressed in all analyzed conditions; CGS1 and UBC are stably expressed under conditions of dehydration stress; and MAP, UBC, and CGS1 are stably expressed under conditions of temperature stress.

CONCLUSION: We have identified appropriate reference genes for RT-qPCR in P. yezoensis under different abiotic stress conditions which will facilitate studies of gene expression under these conditions.}, } @article {pmid29653508, year = {2018}, author = {Hu, X and Ke, L and Wang, Z and Zeng, Z}, title = {Dynamic transcriptome landscape of Asian domestic honeybee (Apis cerana) embryonic development revealed by high-quality RNA sequencing.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {11}, pmid = {29653508}, issn = {1471-213X}, support = {31572469//the National Natural Science Foundation of China/International ; CARS-44-KXJ15//the Earmarked Fund for China Agriculture Research System/International ; GJJ150415//Jiangxi Provincial Education Department Research Project/International ; }, abstract = {BACKGROUND: Honeybee development consists of four stages: embryo, larva, pupa and adult. Embryogenesis, a key process of cell division and differentiation, takes 3 days in honeybees. However, the embryonic transcriptome and the dynamic regulation of embryonic transcription are still largely uncharacterized in honeybees, especially in the Asian honeybee (Apis cerana). Here, we employed high-quality RNA-seq to explore the transcriptome of Asian honeybee embryos at three ages, approximately 24, 48 and 72 h (referred to as Day1, Day2 and Day3, respectively).

RESULTS: Nine embryo samples, three from each age, were collected for RNA-seq. According to the staging scheme of honeybee embryos and the morphological features we observed, our Day1, Day2 and Day3 embryos likely corresponded to the late stage four, stage eight and stage ten development stages, respectively. Hierarchical clustering and principal component analysis showed that same-age samples were grouped together, and the Day2 samples had a closer relationship with the Day3 samples than the Day1 samples. Finally, a total of 18,284 genes harboring 55,646 transcripts were detected in the A. cerana embryos, of which 44.5% consisted of the core transcriptome shared by all three ages of embryos. A total of 4088 upregulated and 3046 downregulated genes were identified among the three embryo ages, of which 2010, 3177 and 1528 genes were upregulated and 2088, 2294 and 303 genes were downregulated from Day1 to Day2, from Day1 to Day3 and from Day2 to Day3, respectively. The downregulated genes were mostly involved in cellular, biosynthetic and metabolic processes, gene expression and protein localization, and macromolecule modification; the upregulated genes mainly participated in cell development and differentiation, tissue, organ and system development, and morphogenesis. Interestingly, several biological processes related to the response to and detection of light stimuli were enriched in the first-day A. cerana embryogenesis but not in the Apis mellifera embryogenesis, which was valuable for further investigations.

CONCLUSIONS: Our transcriptomic data substantially expand the number of known transcribed elements in the A. cerana genome and provide a high-quality view of the transcriptome dynamics of A. cerana embryonic development.}, } @article {pmid29653505, year = {2018}, author = {Gcebe, N and Michel, AL and Hlokwe, TM}, title = {Non-tuberculous Mycobacterium species causing mycobacteriosis in farmed aquatic animals of South Africa.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {32}, pmid = {29653505}, issn = {1471-2180}, abstract = {BACKGROUND: Mycobacteriosis caused by non-tuberculous mycobacteria (NTM), is among the most chronic diseases of aquatic animals. In addition, fish mycobacteriosis has substantial economic consequences especially in the aquaculture and fisheries industry as infections may significantly decrease production and trade. Some fish NTM pathogens are highly virulent and zoonotic; as such, infection of aquaria with these pathogens is a public health concern. In this study, we report isolation of nine different NTM species from sixteen aquatic animals including different fish species, frogs and a crocodile. Given the clinical significance of Mycobacterium marinum and its close relation to Mycobacterium tuberculosis, as well as the significance of ESAT 6 and CFP-10 secretion in mycobacterial virulence, we analysed the esxA and esxB nucleotide sequences of M. marinum isolates identified in this study as well as other mycobacteria in the public databases.

RESULTS: Mycobacterium shimoidei, Mycobacterium marinum, Mycobacterium chelonae, Mycobacterium septicum /M. peregrinum and Mycobacterium porcinum were isolated from gold fish, Guppy, exotic fish species in South Africa, koi and undefined fish, Knysna seahorse, as well Natal ghost frogs respectively, presenting tuberculosis like granuloma. Other NTM species were isolated from the studied aquatic animals without any visible lesions, and these include Mycobacterium sp. N845 T, Mycobacterium fortuitum, a member of the Mycobacterium avium complex, and Mycobacterium szulgai. Phylogenetic analysis of mycobacteria, based on esxA and esxB genes, separated slow growing from rapidly growing mycobacteria as well as pathogenic from non-pathogenic mycobacteria in some cases.

CONCLUSIONS: Isolation of the different NTM species from samples presenting granuloma suggests the significance of these NTM species in causing mycobacteriosis in these aquatic animals. The study also revealed the potential of esxA and esxB sequences as markers for phylogenetic classification of mycobacteria. Observations regarding use of esxA and esxB sequences for prediction of potential pathogenicity of mycobacteria warrants further investigation of these two genes in a study employing NTM species with well-defined pathogenicity.}, } @article {pmid29653175, year = {2018}, author = {Appelhans, MS and Reichelt, N and Groppo, M and Paetzold, C and Wen, J}, title = {Phylogeny and biogeography of the pantropical genus Zanthoxylum and its closest relatives in the proto-Rutaceae group (Rutaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {31-44}, doi = {10.1016/j.ympev.2018.04.013}, pmid = {29653175}, issn = {1095-9513}, mesh = {*Phylogeny ; *Phylogeography ; *Tropical Climate ; Zanthoxylum/*classification ; }, abstract = {Zanthoxylum L. (prickly ash) is the only genus in the Citrus L. family (Rutaceae) with a pantropical distribution. We present the first detailed phylogenetic and biogeographic study of the genus and its close relatives in the proto-Rutaceae group. Our phylogenetic analyses based on two plastid and two nuclear markers show that the genus Toddalia Juss. is nested within Zanthoxylum, that earlier generic and intrageneric classifications need revision, and that the homochlamydeous flowers of the temperate species of Zanthoxylum are the result of a reduction from heterochlamydeous flowers. The biogeographic analyses reveal a Eurasian origin of Zanthoxylum in the Paleocene or Eocene with successive intercontinental or long-range migrations. Zanthoxylum likely crossed the North Atlantic Land Bridges to colonize the Americas in the Eocene, and migrated back to the Old World probably via the Bering Land Bridge in the Oligocene or Miocene. Zanthoxylum also colonized several Pacific Islands and the Hawaiian clade shows phylogenetic incongruence between the plastid and nuclear datasets, suggesting hybridization. The Hawaiian species are one of the rare examples of endemic Hawaiian lineages that are older than the current main islands.}, } @article {pmid29653174, year = {2018}, author = {Seo, MG and Ouh, IO and Kwon, OD and Kwak, D}, title = {Molecular detection of Anaplasma phagocytophilum-like Anaplasma spp. and pathogenic A. Phagocytophilum in cattle from South Korea.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {23-30}, doi = {10.1016/j.ympev.2018.04.012}, pmid = {29653174}, issn = {1095-9513}, mesh = {Anaplasma phagocytophilum/*genetics ; Anaplasmosis/genetics/microbiology ; Animals ; Cattle/*microbiology ; DNA, Bacterial/genetics ; Geography ; Phylogeny ; Polymerase Chain Reaction ; Polymorphism, Restriction Fragment Length/genetics ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; }, abstract = {Anaplasma phagocytophilum is the causative agent of human granulocytic anaplasmosis and tick-borne fever in domestic ruminants. Differential diagnosis of zoonotic and pathogenic tick-borne diseases like granulocytic anaplasmosis is important for the efficient implementation of control programs. Thus, the differentiation of pathogenic A. phagocytophilum from non-pathogenic A. phagocytophilum-like (APL) Anaplasma spp. is essential. Recent molecular analyses of APL revealed its distinct phylogenetic position from A. phagocytophilum. This study was conducted to detect A. phagocytophilum and genetically related strains in 764 cattle in South Korea using PCR and restriction fragment length polymorphism assays. APL clade A and A. phagocytophilum were identified in 20 (2.6%) and 16 (2.1%) cattle, respectively, with 16 cattle (2.1%) displaying co-infection. The 16S rRNA sequences of APL clade A were similar (98.3-99.9%) to those clustered in the APL clade A from eastern Asia. The A. phagocytophilum 16S rRNA sequence shared 98.6-100% identity to those of the A. phagocytophilum group. We used PCR to amplify the groEL and msp2 genes from the 20 samples positive for the 16S rRNA gene and found that 16 were positive for the groEL sequences in the APL clade A, which showed identity (82.8-84.4%) to those clustered in the APL clade A from Japan. Amplification of msp2 was unsuccessful. The co-infection results suggested sequence diversity in Anaplasma spp. Till date, both A. phagocytophilum and APL have been reported to be distributed separately in several animals throughout South Korea. This report is the first co-detection of A. phagocytophilum and APL in Korean cattle using molecular methods. Further studies are needed to provide additional molecular background and trace the evolutionary tree of Anaplasma species in animals and ticks.}, } @article {pmid29653088, year = {2018}, author = {Rogers, KW and Müller, P}, title = {Nodal and BMP dispersal during early zebrafish development.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.04.002}, pmid = {29653088}, issn = {1095-564X}, abstract = {The secreted TGF-β superfamily signals Nodal and BMP coordinate the patterning of vertebrate embryos. Nodal specifies endoderm and mesoderm during germ layer formation, and BMP specifies ventral fates and patterns the dorsal/ventral axis. Five major models have been proposed to explain how the correct distributions of Nodal and BMP are achieved within tissues to orchestrate embryogenesis: source/sink, transcriptional determination, relay, self-regulation, and shuttling. Here, we discuss recent experiments probing these signal dispersal models, focusing on early zebrafish development.}, } @article {pmid29652519, year = {2018}, author = {Sukasem, C and Katsila, T and Tempark, T and Patrinos, GP and Chantratita, W}, title = {Drug-Induced Stevens-Johnson Syndrome and Toxic Epidermal Necrolysis Call for Optimum Patient Stratification and Theranostics via Pharmacogenomics.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {329-353}, doi = {10.1146/annurev-genom-083115-022324}, pmid = {29652519}, issn = {1545-293X}, abstract = {The Global Genomic Medicine Collaborative, a multinational coalition of genomic and policy experts working to implement genomics in clinical care, considers pharmacogenomics to be among the first areas in genomic medicine that can provide guidance in routine clinical practice, by linking genetic variation and drug response. Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are severe life-threatening reactions to medications with a high incidence worldwide. Genomic screening prior to drug administration is a key opportunity and potential paradigm for using genomic medicine to reduce morbidity and mortality and ultimately eliminate one of the most devastating adverse drug reactions. This review focuses on the current understanding of the surveillance, pathogenesis, and treatment of SJS/TEN, including the role of genomics and pharmacogenomics in the etiology, treatment, and eradication of preventable causes of drug-induced SJS/TEN. Gaps, unmet needs, and priorities for future research have been identified for the optimal management of drug-induced SJS/TEN in various ethnic populations. Pharmacogenomics holds great promise for optimal patient stratification and theranostics, yet its clinical implementation needs to be cost-effective and sustainable.}, } @article {pmid29652515, year = {2018}, author = {Bard, JAM and Goodall, EA and Greene, ER and Jonsson, E and Dong, KC and Martin, A}, title = {Structure and Function of the 26S Proteasome.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {697-724}, doi = {10.1146/annurev-biochem-062917-011931}, pmid = {29652515}, issn = {1545-4509}, abstract = {As the endpoint for the ubiquitin-proteasome system, the 26S proteasome is the principal proteolytic machine responsible for regulated protein degradation in eukaryotic cells. The proteasome's cellular functions range from general protein homeostasis and stress response to the control of vital processes such as cell division and signal transduction. To reliably process all the proteins presented to it in the complex cellular environment, the proteasome must combine high promiscuity with exceptional substrate selectivity. Recent structural and biochemical studies have shed new light on the many steps involved in proteasomal substrate processing, including recognition, deubiquitination, and ATP-driven translocation and unfolding. In addition, these studies revealed a complex conformational landscape that ensures proper substrate selection before the proteasome commits to processive degradation. These advances in our understanding of the proteasome's intricate machinery set the stage for future studies on how the proteasome functions as a major regulator of the eukaryotic proteome.}, } @article {pmid29651555, year = {2018}, author = {Hein, H and Scholtz, G}, title = {Larval neurogenesis in the copepod Tigriopus californicus (Tetraconata, Multicrustacea).}, journal = {Development genes and evolution}, volume = {228}, number = {2}, pages = {119-129}, pmid = {29651555}, issn = {1432-041X}, mesh = {Animals ; *Biological Evolution ; Cell Differentiation ; Cells, Cultured ; Copepoda/embryology/genetics/*growth & development/*physiology ; Larva/growth & development/physiology ; Neural Stem Cells/cytology/physiology ; *Neurogenesis ; Phylogeny ; }, abstract = {Arthropod early neurogenesis shows distinct patterns that have been interpreted in an evolutionary framework. For instance, crustaceans and Hexapoda form the taxon Tetraconata and share the differentiation of specific neural precursors, the neuroblasts, a character which sets them apart from Chelicerata and Myriapoda. Neuroblasts are relatively large stem cells that generate ganglion mother cells by asymmetric divisions. Ganglion mother cells typically divide once to give rise to neurons and glia cells. In hexapods, neuroblasts segregate from the neuroectoderm before they begin their characteristic proliferative activity. In the crustaceans studied so far, neuroblasts remain in the neuroectoderm. Yet, detailed studies on early neurogenesis of crustaceans at the cellular level are largely restricted to some malacostracan and branchiopod species. Crustaceans are very diverse and likely paraphyletic with respect to hexapods. Hence, knowledge about neural differentiation in other crustacean taxa might contribute to the understanding of evolution of neurogenesis in Tetraconata. Here, we describe the early neurogenesis during naupliar development of the copepod Tigriopus californicus. We show that neuroblasts are present that generate ganglion mother cells, which in turn divide to give rise to neurons of the ventral nerve cord. These two neural precursor cell types and their specific arrangement correspond to what has been found in other crustaceans. One obvious difference concerns the relative size of the neuroblasts, which are not much larger than their progeny. Our results complement the picture of neural differentiation in crustaceans and suggest that superficially located neuroblasts are likely the ancestral condition in Tetraconata.}, } @article {pmid29651552, year = {2018}, author = {Zapata, B and Alvarez, DN and Farah, S and Garcia-de-la-Maria, C and Miro, JM and Sakoulas, G and Bayer, AS and Mishra, NN}, title = {Prevention of High-Level Daptomycin-Resistance Emergence In Vitro in Streptococcus mitis-oralis by Using Combination Antimicrobial Strategies.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1062-1067}, pmid = {29651552}, issn = {1432-0991}, support = {1RO1AI130056-01//NIH-NIAID/ ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Cephalosporins/pharmacology ; Daptomycin/*pharmacology ; Drug Combinations ; Drug Resistance, Bacterial ; Gentamicins/pharmacology ; Humans ; Imipenem/pharmacology ; Linezolid/pharmacology ; Microbial Sensitivity Tests ; Organophosphates/pharmacology ; Oxazoles/pharmacology ; Rifampin/pharmacology ; Streptococcus mitis/*drug effects ; Streptococcus oralis/*drug effects ; Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology ; }, abstract = {Among the viridans group streptococci, S. mitis-oralis strains are frequently resistant to multiple β-lactams and tolerant to vancomycin (VAN). This scenario has led to the proposed clinical use of newer agents, like daptomycin (DAP) for such S. mitis-oralis strains. However, recent recognition of the rapid and durable emergence of high-level DAP-resistance (DAP-R; DAP MICs > 256 µg/ml) induced by DAP exposures in vitro and in vivo has dampened enthusiasm for such approaches. In this study, we evaluated a broad range of DAP combination regimens in vitro for their capacity to prevent emergence of high-level DAP-R in a prototype S. mitis-oralis strain (351) during serial passage experiments, including DAP + either gentamicin (GEN), rifampin (RIF), trimethoprim-sulfamethoxazole (TMP-SMX), imipenem (IMP), ceftaroline (CPT), tedizolid (TDZ), or linezolid (LDZ). In addition, we assessed selected DAP combination regimens for their ability to exert either an early bactericidal impact and/or synergistically kill the S. mitis-oralis study strain. During serial passage, three of the eight antibiotic combinations (DAP + GEN, CPT, or TMP- SMX) exhibited significantly reduced DAP MICs (≈ by 8-40 fold) vs serial exposure in DAP alone (DAP MICs > 256 µg/ml). In addition, combinations of DAP + GEN and DAP + CPT were both bactericidal and synergistic in early time-kill curve interactions.}, } @article {pmid29651551, year = {2018}, author = {Herman, A}, title = {Antimicrobial Ingredients as Preservative Booster and Components of Self-Preserving Cosmetic Products.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1492-2}, pmid = {29651551}, issn = {1432-0991}, abstract = {This review reports cosmetic ingredients with antimicrobial activity including synthetic and natural (plant and microbial) origin as alternative for preservatives used in cosmetics as well described mechanism of their action.}, } @article {pmid29651100, year = {2018}, author = {Burgess, DJ}, title = {Transcriptomics: Finding structure in gene expression.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {249}, pmid = {29651100}, issn = {1471-0064}, } @article {pmid29650704, year = {2018}, author = {Srivastava, AP and Luo, M and Zhou, W and Symersky, J and Bai, D and Chambers, MG and Faraldo-Gómez, JD and Liao, M and Mueller, DM}, title = {High-resolution cryo-EM analysis of the yeast ATP synthase in a lipid membrane.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6389}, pages = {}, pmid = {29650704}, issn = {1095-9203}, support = {R01 GM066223/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/biosynthesis ; Cryoelectron Microscopy ; Membrane Lipids/chemistry ; Mitochondrial Membranes/chemistry/*enzymology ; Mitochondrial Proton-Translocating ATPases/*chemistry/ultrastructure ; Molecular Motor Proteins/*chemistry/ultrastructure ; Oligomycins/chemistry ; Protein Conformation ; Protein Subunits ; Saccharomyces cerevisiae Proteins/*chemistry/ultrastructure ; Single Molecule Imaging ; }, abstract = {Mitochondrial adenosine triphosphate (ATP) synthase comprises a membrane embedded Fo motor that rotates to drive ATP synthesis in the F1 subunit. We used single-particle cryo-electron microscopy (cryo-EM) to obtain structures of the full complex in a lipid bilayer in the absence or presence of the inhibitor oligomycin at 3.6- and 3.8-angstrom resolution, respectively. To limit conformational heterogeneity, we locked the rotor in a single conformation by fusing the F6 subunit of the stator with the δ subunit of the rotor. Assembly of the enzyme with the F6-δ fusion caused a twisting of the rotor and a 9° rotation of the Fo c10-ring in the direction of ATP synthesis, relative to the structure of isolated Fo Our cryo-EM structures show how F1 and Fo are coupled, give insight into the proton translocation pathway, and show how oligomycin blocks ATP synthesis.}, } @article {pmid29650703, year = {2018}, author = {Langdon, EM and Qiu, Y and Ghanbari Niaki, A and McLaughlin, GA and Weidmann, CA and Gerbich, TM and Smith, JA and Crutchley, JM and Termini, CM and Weeks, KM and Myong, S and Gladfelter, AS}, title = {mRNA structure determines specificity of a polyQ-driven phase separation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {922-927}, pmid = {29650703}, issn = {1095-9203}, support = {T32 CA009156/CA/NCI NIH HHS/United States ; R35 GM122532/GM/NIGMS NIH HHS/United States ; DP2 GM105453/GM/NIGMS NIH HHS/United States ; R01 GM081506/GM/NIGMS NIH HHS/United States ; R01 GM115631/GM/NIGMS NIH HHS/United States ; }, mesh = {Base Sequence ; Cyclins/chemistry ; Nucleic Acid Conformation ; Peptides/*chemistry ; *Phase Transition ; RNA, Messenger/*chemistry ; RNA-Binding Proteins/*chemistry ; Saccharomyces cerevisiae Proteins/*chemistry ; }, abstract = {RNA promotes liquid-liquid phase separation (LLPS) to build membraneless compartments in cells. How distinct molecular compositions are established and maintained in these liquid compartments is unknown. Here, we report that secondary structure allows messenger RNAs (mRNAs) to self-associate and determines whether an mRNA is recruited to or excluded from liquid compartments. The polyQ-protein Whi3 induces conformational changes in RNA structure and generates distinct molecular fluctuations depending on the RNA sequence. These data support a model in which structure-based, RNA-RNA interactions promote assembly of distinct droplets and protein-driven, conformational dynamics of the RNA maintain this identity. Thus, the shape of RNA can promote the formation and coexistence of the diverse array of RNA-rich liquid compartments found in a single cell.}, } @article {pmid29650702, year = {2018}, author = {Maharana, S and Wang, J and Papadopoulos, DK and Richter, D and Pozniakovsky, A and Poser, I and Bickle, M and Rizk, S and Guillén-Boixet, J and Franzmann, TM and Jahnel, M and Marrone, L and Chang, YT and Sterneckert, J and Tomancak, P and Hyman, AA and Alberti, S}, title = {RNA buffers the phase separation behavior of prion-like RNA binding proteins.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {918-921}, pmid = {29650702}, issn = {1095-9203}, support = {MC_PC_U127580972//Medical Research Council/United Kingdom ; }, mesh = {Cell Nucleus/*chemistry ; Cytoplasm/*chemistry ; HeLa Cells ; Humans ; Lipid Droplets ; Phase Transition ; Prions/*chemistry ; Protein Aggregates ; Protein Aggregation, Pathological/*metabolism ; RNA, Nuclear/*chemistry ; RNA-Binding Proteins/*chemistry ; Solubility ; }, abstract = {Prion-like RNA binding proteins (RBPs) such as TDP43 and FUS are largely soluble in the nucleus but form solid pathological aggregates when mislocalized to the cytoplasm. What keeps these proteins soluble in the nucleus and promotes aggregation in the cytoplasm is still unknown. We report here that RNA critically regulates the phase behavior of prion-like RBPs. Low RNA/protein ratios promote phase separation into liquid droplets, whereas high ratios prevent droplet formation in vitro. Reduction of nuclear RNA levels or genetic ablation of RNA binding causes excessive phase separation and the formation of cytotoxic solid-like assemblies in cells. We propose that the nucleus is a buffered system in which high RNA concentrations keep RBPs soluble. Changes in RNA levels or RNA binding abilities of RBPs cause aberrant phase transitions.}, } @article {pmid29650701, year = {2018}, author = {Ghadimi, AH and Fedorov, SA and Engelsen, NJ and Bereyhi, MJ and Schilling, R and Wilson, DJ and Kippenberg, TJ}, title = {Elastic strain engineering for ultralow mechanical dissipation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {764-768}, doi = {10.1126/science.aar6939}, pmid = {29650701}, issn = {1095-9203}, abstract = {Extreme stresses can be produced in nanoscale structures; this feature has been used to realize enhanced materials properties, such as the high mobility of silicon in modern transistors. We show how nanoscale stress can be used to realize exceptionally low mechanical dissipation when combined with "soft-clamping"-a form of phononic engineering. Specifically, using a nonuniform phononic crystal pattern, we colocalize the strain and flexural motion of a free-standing silicon nitride nanobeam. Ringdown measurements at room temperature reveal string-like vibrational modes with quality (Q) factors as high as 800 million and Q × frequency exceeding 1015 hertz. These results illustrate a promising route for engineering ultracoherent nanomechanical devices.}, } @article {pmid29650700, year = {2018}, author = {Liu, LR and Hood, JD and Yu, Y and Zhang, JT and Hutzler, NR and Rosenband, T and Ni, KK}, title = {Building one molecule from a reservoir of two atoms.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6391}, pages = {900-903}, doi = {10.1126/science.aar7797}, pmid = {29650700}, issn = {1095-9203}, abstract = {Chemical reactions typically proceed via stochastic encounters between reactants. Going beyond this paradigm, we combined exactly two atoms in a single, controlled reaction. The experimental apparatus traps two individual laser-cooled atoms [one sodium (Na) and one cesium (Cs)] in separate optical tweezers and then merges them into one optical dipole trap. Subsequently, photoassociation forms an excited-state NaCs molecule. The discovery of previously unseen resonances near the molecular dissociation threshold and measurement of collision rates are enabled by the tightly trapped ultracold sample of atoms. As laser-cooling and trapping capabilities are extended to more elements, the technique will enable the study of more diverse, and eventually more complex, molecules in an isolated environment, as well as synthesis of designer molecules for qubits.}, } @article {pmid29650675, year = {2018}, author = {Sanganyado, E}, title = {My path to contentment.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {234}, doi = {10.1126/science.360.6385.234}, pmid = {29650675}, issn = {1095-9203}, } @article {pmid29650674, year = {2018}, author = {Burnett, DL and Langley, DB and Schofield, P and Hermes, JR and Chan, TD and Jackson, J and Bourne, K and Reed, JH and Patterson, K and Porebski, BT and Brink, R and Christ, D and Goodnow, CC}, title = {Germinal center antibody mutation trajectories are determined by rapid self/foreign discrimination.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {223-226}, pmid = {29650674}, issn = {1095-9203}, support = {MC_U105178804//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Antibodies/chemistry/*genetics/immunology ; Antibody Affinity/genetics ; Antibody Formation/*genetics ; Autoantigens/*immunology ; B-Lymphocytes/immunology ; Clonal Anergy ; Cross Reactions ; Crystallography, X-Ray ; Germinal Center/*immunology ; Mice ; Mice, Mutant Strains ; Molecular Mimicry/*genetics ; Mutation ; Nucleoproteins/genetics/immunology ; Selection, Genetic ; *Self Tolerance ; Single-Cell Analysis ; }, abstract = {Antibodies have the specificity to differentiate foreign antigens that mimic self antigens, but it remains unclear how such specificity is acquired. In a mouse model, we generated B cells displaying an antibody that cross-reacts with two related protein antigens expressed on self versus foreign cells. B cell anergy was imposed by self antigen but reversed upon challenge with high-density foreign antigen, leading to germinal center recruitment and antibody gene hypermutation. Single-cell analysis detected rapid selection for mutations that decrease self affinity and slower selection for epistatic mutations that specifically increase foreign affinity. Crystal structures revealed that these mutations exploited subtle topological differences to achieve 5000-fold preferential binding to foreign over self epitopes. Resolution of antigenic mimicry drove the optimal affinity maturation trajectory, highlighting the value of retaining self-reactive clones as substrates for protective antibody responses.}, } @article {pmid29650673, year = {2018}, author = {Hemingway, JD and Hilton, RG and Hovius, N and Eglinton, TI and Haghipour, N and Wacker, L and Chen, MC and Galy, VV}, title = {Microbial oxidation of lithospheric organic carbon in rapidly eroding tropical mountain soils.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {209-212}, doi = {10.1126/science.aao6463}, pmid = {29650673}, issn = {1095-9203}, mesh = {Carbon/*metabolism ; Carbon Dioxide/metabolism ; Organic Chemicals/*metabolism ; Oxidation-Reduction ; Soil/*chemistry ; *Soil Microbiology ; Taiwan ; }, abstract = {Lithospheric organic carbon ("petrogenic"; OCpetro) is oxidized during exhumation and subsequent erosion of mountain ranges. This process is a considerable source of carbon dioxide (CO2) to the atmosphere over geologic time scales, but the mechanisms that govern oxidation rates in mountain landscapes are poorly constrained. We demonstrate that, on average, 67 ± 11% of the OCpetro initially present in bedrock exhumed from the tropical, rapidly eroding Central Range of Taiwan is oxidized in soils, leading to CO2 emissions of 6.1 to 18.6 metric tons of carbon per square kilometer per year. The molecular and isotopic evolution of bulk OC and lipid biomarkers during soil formation reveals that OCpetro remineralization is microbially mediated. Rapid oxidation in mountain soils drives CO2 emission fluxes that increase with erosion rate, thereby counteracting CO2 drawdown by silicate weathering and biospheric OC burial.}, } @article {pmid29650672, year = {2018}, author = {Wilen, CB and Lee, S and Hsieh, LL and Orchard, RC and Desai, C and Hykes, BL and McAllaster, MR and Balce, DR and Feehley, T and Brestoff, JR and Hickey, CA and Yokoyama, CC and Wang, YT and MacDuff, DA and Kreamalmayer, D and Howitt, MR and Neil, JA and Cadwell, K and Allen, PM and Handley, SA and van Lookeren Campagne, M and Baldridge, MT and Virgin, HW}, title = {Tropism for tuft cells determines immune promotion of norovirus pathogenesis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {204-208}, pmid = {29650672}, issn = {1095-9203}, support = {K01 DK113041/DK/NIDDK NIH HHS/United States ; U19 AI109725/AI/NIAID NIH HHS/United States ; R01 DK093668/DK/NIDDK NIH HHS/United States ; R01 AI127552/AI/NIAID NIH HHS/United States ; K22 AI127846/AI/NIAID NIH HHS/United States ; K99 DK116666/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; T32 AI007163/AI/NIAID NIH HHS/United States ; R01 AI121244/AI/NIAID NIH HHS/United States ; K08 AI128043/AI/NIAID NIH HHS/United States ; R01 DK103788/DK/NIDDK NIH HHS/United States ; P30 DK052574/DK/NIDDK NIH HHS/United States ; R01 HL123340/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Caliciviridae Infections/*immunology ; Cell Proliferation ; Cytokines/metabolism ; Enterocytes/*immunology/*virology ; Mice ; Microbiota/*immunology ; Norovirus/*physiology ; Receptors, Immunologic/metabolism ; Viral Tropism/*immunology ; }, abstract = {Complex interactions between host immunity and the microbiome regulate norovirus infection. However, the mechanism of host immune promotion of enteric virus infection remains obscure. The cellular tropism of noroviruses is also unknown. Recently, we identified CD300lf as a murine norovirus (MNoV) receptor. In this study, we have shown that tuft cells, a rare type of intestinal epithelial cell, express CD300lf and are the target cell for MNoV in the mouse intestine. We found that type 2 cytokines, which induce tuft cell proliferation, promote MNoV infection in vivo. These cytokines can replace the effect of commensal microbiota in promoting virus infection. Our work thus provides insight into how the immune system and microbes can coordinately promote enteric viral infection.}, } @article {pmid29650671, year = {2018}, author = {Moreno, C and Vilas-Varela, M and Kretz, B and Garcia-Lekue, A and Costache, MV and Paradinas, M and Panighel, M and Ceballos, G and Valenzuela, SO and Peña, D and Mugarza, A}, title = {Bottom-up synthesis of multifunctional nanoporous graphene.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {199-203}, doi = {10.1126/science.aar2009}, pmid = {29650671}, issn = {1095-9203}, abstract = {Nanosize pores can turn semimetallic graphene into a semiconductor and, from being impermeable, into the most efficient molecular-sieve membrane. However, scaling the pores down to the nanometer, while fulfilling the tight structural constraints imposed by applications, represents an enormous challenge for present top-down strategies. Here we report a bottom-up method to synthesize nanoporous graphene comprising an ordered array of pores separated by ribbons, which can be tuned down to the 1-nanometer range. The size, density, morphology, and chemical composition of the pores are defined with atomic precision by the design of the molecular precursors. Our electronic characterization further reveals a highly anisotropic electronic structure, where orthogonal one-dimensional electronic bands with an energy gap of ∼1 electron volt coexist with confined pore states, making the nanoporous graphene a highly versatile semiconductor for simultaneous sieving and electrical sensing of molecular species.}, } @article {pmid29650670, year = {2018}, author = {Neill, C and Roushan, P and Kechedzhi, K and Boixo, S and Isakov, SV and Smelyanskiy, V and Megrant, A and Chiaro, B and Dunsworth, A and Arya, K and Barends, R and Burkett, B and Chen, Y and Chen, Z and Fowler, A and Foxen, B and Giustina, M and Graff, R and Jeffrey, E and Huang, T and Kelly, J and Klimov, P and Lucero, E and Mutus, J and Neeley, M and Quintana, C and Sank, D and Vainsencher, A and Wenner, J and White, TC and Neven, H and Martinis, JM}, title = {A blueprint for demonstrating quantum supremacy with superconducting qubits.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {195-199}, doi = {10.1126/science.aao4309}, pmid = {29650670}, issn = {1095-9203}, abstract = {A key step toward demonstrating a quantum system that can address difficult problems in physics and chemistry will be performing a computation beyond the capabilities of any classical computer, thus achieving so-called quantum supremacy. In this study, we used nine superconducting qubits to demonstrate a promising path toward quantum supremacy. By individually tuning the qubit parameters, we were able to generate thousands of distinct Hamiltonian evolutions and probe the output probabilities. The measured probabilities obey a universal distribution, consistent with uniformly sampling the full Hilbert space. As the number of qubits increases, the system continues to explore the exponentially growing number of states. Extending these results to a system of 50 qubits has the potential to address scientific questions that are beyond the capabilities of any classical computer.}, } @article {pmid29650669, year = {2018}, author = {Parker, RH and Yu, C and Zhong, W and Estey, B and Müller, H}, title = {Measurement of the fine-structure constant as a test of the Standard Model.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {191-195}, doi = {10.1126/science.aap7706}, pmid = {29650669}, issn = {1095-9203}, abstract = {Measurements of the fine-structure constant α require methods from across subfields and are thus powerful tests of the consistency of theory and experiment in physics. Using the recoil frequency of cesium-133 atoms in a matter-wave interferometer, we recorded the most accurate measurement of the fine-structure constant to date: α = 1/137.035999046(27) at 2.0 × 10-10 accuracy. Using multiphoton interactions (Bragg diffraction and Bloch oscillations), we demonstrate the largest phase (12 million radians) of any Ramsey-Bordé interferometer and control systematic effects at a level of 0.12 part per billion. Comparison with Penning trap measurements of the electron gyromagnetic anomaly ge - 2 via the Standard Model of particle physics is now limited by the uncertainty in ge - 2; a 2.5σ tension rejects dark photons as the reason for the unexplained part of the muon's magnetic moment at a 99% confidence level. Implications for dark-sector candidates and electron substructure may be a sign of physics beyond the Standard Model that warrants further investigation.}, } @article {pmid29650668, year = {2018}, author = {Jefferson, AJ and Kenney, MA}, title = {Efforts large and small speed science reform.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {164}, doi = {10.1126/science.aat6341}, pmid = {29650668}, issn = {1095-9203}, mesh = {*Health Care Reform ; *Science ; }, } @article {pmid29650667, year = {2018}, author = {}, title = {SciComm speaks.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {163}, doi = {10.1126/science.aat7933}, pmid = {29650667}, issn = {1095-9203}, } @article {pmid29650666, year = {2018}, author = {Zaringhalam, M and Vijayaraghavan, R and Simonis, J and Ramirez, K and Zelikova, J and , }, title = {Journal editors should not divide scientists.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {163-164}, doi = {10.1126/science.aat6288}, pmid = {29650666}, issn = {1095-9203}, mesh = {*Editorial Policies ; Humans ; Periodicals as Topic ; *Publishing ; }, } @article {pmid29650665, year = {2018}, author = {Yammine, SZ and Liu, C and Jarreau, PB and Coe, IR}, title = {Social media for social change in science.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {162-163}, doi = {10.1126/science.aat7303}, pmid = {29650665}, issn = {1095-9203}, mesh = {Humans ; Public Opinion ; Science ; *Social Change ; *Social Media ; }, } @article {pmid29650664, year = {2018}, author = {Berg, J}, title = {Editor's note.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {162}, doi = {10.1126/science.aat7935}, pmid = {29650664}, issn = {1095-9203}, } @article {pmid29650663, year = {2018}, author = {Shah, SK and Kimmelman, J and Lyerly, AD and Lynch, HF and Miller, FG and Palacios, R and Pardo, CA and Zorrilla, C}, title = {Bystander risk, social value, and ethics of human research.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {158-159}, doi = {10.1126/science.aaq0917}, pmid = {29650663}, issn = {1095-9203}, mesh = {Aedes/virology ; Animals ; Ethics Committees, Research ; Human Experimentation/*ethics ; Humans ; Risk ; Social Values ; *Zika Virus ; Zika Virus Infection/*transmission ; }, } @article {pmid29650662, year = {2018}, author = {Kimble, J}, title = {John Sulston (1942-2018).}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {157}, doi = {10.1126/science.aat6705}, pmid = {29650662}, issn = {1095-9203}, mesh = {Animals ; Caenorhabditis elegans/genetics ; *Genome, Human ; History, 20th Century ; History, 21st Century ; Humans ; *Nobel Prize ; United Kingdom ; }, } @article {pmid29650661, year = {2018}, author = {Preskill, J}, title = {Stephen Hawking (1942-2018).}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {156}, doi = {10.1126/science.aat6775}, pmid = {29650661}, issn = {1095-9203}, } @article {pmid29650660, year = {2018}, author = {Sinitskii, A}, title = {A recipe for nanoporous graphene.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {154-155}, doi = {10.1126/science.aat5117}, pmid = {29650660}, issn = {1095-9203}, mesh = {*Graphite ; *Nanopores ; Porosity ; }, } @article {pmid29650659, year = {2018}, author = {Lussier, AA and Keinan, A}, title = {Crowdsourced genealogies and genomes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {153-154}, doi = {10.1126/science.aat2634}, pmid = {29650659}, issn = {1095-9203}, support = {R01 GM108805/GM/NIGMS NIH HHS/United States ; R01 HG006849/HG/NHGRI NIH HHS/United States ; }, mesh = {*Crowdsourcing ; *Genealogy and Heraldry ; Humans ; }, } @article {pmid29650658, year = {2018}, author = {Kara, EE and Nussenzweig, MC}, title = {Redemption for self-reactive antibodies.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {152-153}, doi = {10.1126/science.aat5758}, pmid = {29650658}, issn = {1095-9203}, mesh = {*Autoantibodies ; Humans ; }, } @article {pmid29650657, year = {2018}, author = {Ho, JML and Bennett, MR}, title = {Improved memory devices for synthetic cells.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {150-151}, doi = {10.1126/science.aat3236}, pmid = {29650657}, issn = {1095-9203}, mesh = {*Artificial Cells ; Humans ; *Memory ; }, } @article {pmid29650656, year = {2018}, author = {Samset, BH}, title = {How cleaner air changes the climate.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {148-150}, doi = {10.1126/science.aat1723}, pmid = {29650656}, issn = {1095-9203}, mesh = {*Air Pollution ; *Climate Change ; *Greenhouse Effect ; }, } @article {pmid29650655, year = {2018}, author = {Waldrop, MM}, title = {Free agents.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {144-147}, doi = {10.1126/science.360.6385.144}, pmid = {29650655}, issn = {1095-9203}, mesh = {*Computer Simulation ; *Disasters ; Humans ; }, } @article {pmid29650654, year = {2018}, author = {Pennisi, E}, title = {Human mutation rate a legacy from our past.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {143}, doi = {10.1126/science.360.6385.143}, pmid = {29650654}, issn = {1095-9203}, mesh = {Animals ; *Genetic Variation ; *Genome, Human ; Humans ; *Mutation Rate ; Species Specificity ; }, } @article {pmid29650653, year = {2018}, author = {Yasinski, E}, title = {Study questions animal efficacy data behind trials.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {142}, doi = {10.1126/science.360.6385.142}, pmid = {29650653}, issn = {1095-9203}, mesh = {Animal Experimentation/*ethics ; Animals ; Clinical Trials as Topic ; *Drug Approval ; Drug Evaluation/*ethics ; *Drugs, Investigational ; *Ethical Review ; Humans ; }, } @article {pmid29650652, year = {2018}, author = {Lawler, A}, title = {Ancient sites savaged in Yemen, Iraq.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {140-141}, doi = {10.1126/science.360.6385.140}, pmid = {29650652}, issn = {1095-9203}, } @article {pmid29650651, year = {2018}, author = {Service, RF}, title = {Chemists seek antiaddiction drugs to battle hijacked brain.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {139-140}, doi = {10.1126/science.360.6385.139}, pmid = {29650651}, issn = {1095-9203}, mesh = {4-Aminobutyrate Transaminase/*antagonists & inhibitors ; Animals ; Behavior, Addictive/*drug therapy ; Brain/*drug effects/physiology ; Craving/*drug effects ; Drug Design ; Enzyme Inhibitors/*chemistry/pharmacology/therapeutic use ; Humans ; Opioid-Related Disorders/*drug therapy/psychology ; Reward ; gamma-Aminobutyric Acid/metabolism ; }, } @article {pmid29650650, year = {2018}, author = {Clery, D}, title = {Alpha Centauri's siren call has frustrated planet hunters.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {138-139}, doi = {10.1126/science.360.6385.138}, pmid = {29650650}, issn = {1095-9203}, } @article {pmid29650649, year = {2018}, author = {Wade, L}, title = {Latin America's lost histories revealed.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {137-138}, doi = {10.1126/science.360.6385.137}, pmid = {29650649}, issn = {1095-9203}, mesh = {*Biological Evolution ; *Genome, Human ; History, 16th Century ; History, 17th Century ; Human Migration/*history ; Humans ; Latin America ; Mexico ; }, } @article {pmid29650648, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {134-136}, doi = {10.1126/science.360.6385.134}, pmid = {29650648}, issn = {1095-9203}, } @article {pmid29650647, year = {2018}, author = {Berg, J}, title = {Obfuscating with transparency.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {133}, doi = {10.1126/science.aat8121}, pmid = {29650647}, issn = {1095-9203}, mesh = {*Policy Making ; United States ; *United States Environmental Protection Agency ; }, } @article {pmid29650646, year = {2018}, author = {}, title = {Erratum for the Report "Predicting reaction performance in C-N cross-coupling using machine learning" by D. T. Ahneman, J. G. Estrada, S. Lin, S. D. Dreher, A. G. Doyle.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {}, doi = {10.1126/science.aat7648}, pmid = {29650646}, issn = {1095-9203}, } @article {pmid29650645, year = {2018}, author = {Weidberg, H and Amon, A}, title = {MitoCPR-A surveillance pathway that protects mitochondria in response to protein import stress.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {}, doi = {10.1126/science.aan4146}, pmid = {29650645}, issn = {1095-9203}, support = {R01 CA118066/CA/NCI NIH HHS/United States ; P30 CA014051/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adenosine Triphosphatases/*metabolism ; Autophagy-Related Proteins/*metabolism ; Mitochondria/*metabolism ; Mitochondrial Membrane Transport Proteins/metabolism ; Peptidyl Transferases/metabolism ; Proteasome Endopeptidase Complex/*metabolism ; Protein Transport ; *Proteolysis ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Stress, Physiological ; }, abstract = {Mitochondrial functions are essential for cell viability and rely on protein import into the organelle. Various disease and stress conditions can lead to mitochondrial import defects. We found that inhibition of mitochondrial import in budding yeast activated a surveillance mechanism, mitoCPR, that improved mitochondrial import and protected mitochondria during import stress. mitoCPR induced expression of Cis1, which associated with the mitochondrial translocase to reduce the accumulation of mitochondrial precursor proteins at the mitochondrial translocase. Clearance of precursor proteins depended on the Cis1-interacting AAA+ adenosine triphosphatase Msp1 and the proteasome, suggesting that Cis1 facilitates degradation of unimported proteins. mitoCPR was required for maintaining mitochondrial functions when protein import was compromised, demonstrating the importance of mitoCPR in protecting the mitochondrial compartment.}, } @article {pmid29650539, year = {2018}, author = {Bell, S and Sah, S and Albright, TD and Gates, SJ and Denton, MB and Casadevall, A}, title = {A call for more science in forensic science.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4541-4544}, pmid = {29650539}, issn = {1091-6490}, mesh = {Criminal Law ; Forensic Sciences/*education/legislation & jurisprudence/*methods ; Humans ; Research ; }, abstract = {Forensic science is critical to the administration of justice. The discipline of forensic science is remarkably complex and includes methodologies ranging from DNA analysis to chemical composition to pattern recognition. Many forensic practices developed under the auspices of law enforcement and were vetted primarily by the legal system rather than being subjected to scientific scrutiny and empirical testing. Beginning in the 1990s, exonerations based on DNA-related methods revealed problems with some forensic disciplines, leading to calls for major reforms. This process generated a National Academy of Science report in 2009 that was highly critical of many forensic practices and eventually led to the establishment of the National Commission for Forensic Science (NCFS) in 2013. The NCFS was a deliberative body that catalyzed communication between nonforensic scientists, forensic scientists, and other stakeholders in the legal community. In 2017, despite continuing problems with forensic science, the Department of Justice terminated the NCFS. Just when forensic science needs the most support, it is getting the least. We urge the larger scientific community to come to the aid of our forensic colleagues by advocating for urgently needed research, testing, and financial support.}, } @article {pmid29650391, year = {2018}, author = {Dietel, AK and Kaltenpoth, M and Kost, C}, title = {Convergent Evolution in Intracellular Elements: Plasmids as Model Endosymbionts.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {755-768}, doi = {10.1016/j.tim.2018.03.004}, pmid = {29650391}, issn = {1878-4380}, abstract = {Endosymbionts are organisms that live inside the cells of other species. This lifestyle is ubiquitous across the tree of life and is featured by unicellular eukaryotes, prokaryotes, and by extrachromosomal genetic elements such as plasmids. Given that all of these elements dwell in the cytoplasm of their host cell, they should be subject to similar selection pressures. Here we show that strikingly similar features have evolved in both bacterial endosymbionts and plasmids. Since host and endosymbiont are often metabolically tightly intertwined, they are difficult to disentangle experimentally. We propose that using plasmids as tractable model systems can help to solve this problem, thus allowing fundamental questions to be experimentally addressed about the ecology and evolution of endosymbiotic interactions.}, } @article {pmid29650366, year = {2018}, author = {Sohrabi, Y and Lipoldová, M}, title = {Mannose Receptor and the Mystery of Nonhealing Leishmania major Infection.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {354-356}, doi = {10.1016/j.pt.2018.03.006}, pmid = {29650366}, issn = {1471-5007}, mesh = {Humans ; Interferon-gamma ; Lectins, C-Type ; *Leishmania major ; *Leishmaniasis, Cutaneous ; Mannose-Binding Lectins ; Receptors, Cell Surface ; }, abstract = {Scientists have long puzzled over the ability of Leishmania major Seidman (LmSd) to form nonhealing cutaneous lesions in the face of a strong Th1 response. A recent study identified a population of dermal macrophages that are preferentially infected by LmSd in a mannose receptor 1-, C-type 1 (MRC1/CD206)-dependent manner.}, } @article {pmid29650327, year = {2018}, author = {Desmond, H}, title = {Natural selection, plasticity, and the rationale for largest-scale trends.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {68-69}, number = {}, pages = {25-33}, doi = {10.1016/j.shpsc.2018.04.002}, pmid = {29650327}, issn = {1879-2499}, mesh = {*Adaptation, Biological ; *Environment ; *Models, Genetic ; *Phenotype ; *Selection, Genetic ; }, abstract = {Many have argued that there is no reason why natural selection should cause directional increases in measures such as body size or complexity across evolutionary history as a whole. In this paper I argue that this conclusion does not hold for selection for adaptations to environmental variability, and that, given the inevitability of environmental variability, trends in adaptations to variability are an expected feature of evolution by natural selection. As a concrete instance of this causal structure, I outline how this may be applied to a trend in phenotypic plasticity.}, } @article {pmid29650046, year = {2018}, author = {Aroke, D and Ngek, LT and Tindong, M and Fomanka, E and Achu, C and Tanah, AA and Kadia, BM}, title = {Blighted ovum and tubal pregnancy: a rare form of heterotopic pregnancy: case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {242}, pmid = {29650046}, issn = {1756-0500}, mesh = {Adult ; Embryo, Mammalian/*abnormalities/diagnostic imaging ; Female ; Humans ; Pregnancy ; Pregnancy, Tubal/*diagnosis/diagnostic imaging/surgery ; }, abstract = {BACKGROUND: Heterotopic pregnancies are rare in spontaneous conceptions. Nonetheless, when it does occur, the intrauterine pregnancy is usually viable. We herein present a true rarity of the coexistence of a blighted ovum and an ectopic pregnancy.

CASE PRESENTATION: A 25 year old G2P1001 married seamstress of African ethnicity at 8 weeks of amenorrhoea presented to our health facility with a 4 day history of lower abdominal pains and vaginal bleeding for which physical examination revealed a closed cervix. Trans-abdominal ultrasound scan confirmed a diagnosis of a blighted ovum and an ectopic pregnancy. Patient was managed with surgical therapy. Evolution thereafter was uneventful.

CONCLUSION: The case presented confirms that HP can occur in the absence of predisposing factors, and that the detection of a blighted ovum should not preclude the possibility of a simultaneous ectopic pregnancy. A high index of suspicion could lead to early diagnosis, prompt management and a favourable prognosis even in a low-income setting.}, } @article {pmid29650016, year = {2018}, author = {Scharm, M and Gebhardt, T and Touré, V and Bagnacani, A and Salehzadeh-Yazdi, A and Wolkenhauer, O and Waltemath, D}, title = {Evolution of computational models in BioModels Database and the Physiome Model Repository.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {53}, pmid = {29650016}, issn = {1752-0509}, support = {FKZ 031 6194//German Federal Ministry of Education and Research (BMBF)/ ; FKZ 031 6194//German Federal Ministry of Education and Research (BMBF)/ ; FKZ 031 6181//German Federal Ministry of Education and Research (BMBF)/ ; FKZ 031 6194//German Federal Ministry of Education and Research (BMBF)/ ; }, abstract = {BACKGROUND: A useful model is one that is being (re)used. The development of a successful model does not finish with its publication. During reuse, models are being modified, i.e. expanded, corrected, and refined. Even small changes in the encoding of a model can, however, significantly affect its interpretation. Our motivation for the present study is to identify changes in models and make them transparent and traceable.

METHODS: We analysed 13734 models from BioModels Database and the Physiome Model Repository. For each model, we studied the frequencies and types of updates between its first and latest release. To demonstrate the impact of changes, we explored the history of a Repressilator model in BioModels Database.

RESULTS: We observed continuous updates in the majority of models. Surprisingly, even the early models are still being modified. We furthermore detected that many updates target annotations, which improves the information one can gain from models. To support the analysis of changes in model repositories we developed MoSt, an online tool for visualisations of changes in models. The scripts used to generate the data and figures for this study are available from GitHub https://github.com/binfalse/BiVeS-StatsGenerator and as a Docker image at https://hub.docker.com/r/binfalse/bives-statsgenerator/ . The website https://most.bio.informatik.uni-rostock.de/ provides interactive access to model versions and their evolutionary statistics.

CONCLUSION: The reuse of models is still impeded by a lack of trust and documentation. A detailed and transparent documentation of all aspects of the model, including its provenance, will improve this situation. Knowledge about a model's provenance can avoid the repetition of mistakes that others already faced. More insights are gained into how the system evolves from initial findings to a profound understanding. We argue that it is the responsibility of the maintainers of model repositories to offer transparent model provenance to their users.}, } @article {pmid29650003, year = {2018}, author = {Jørgensen, KM and Solberg, MF and Besnier, F and Thorsen, A and Fjelldal, PG and Skaala, Ø and Malde, K and Glover, KA}, title = {Judging a salmon by its spots: environmental variation is the primary determinant of spot patterns in Salmo salar.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {14}, pmid = {29650003}, issn = {1472-6785}, support = {200501//Norges Forskningsråd/International ; 216105//Norges Forskningsråd/International ; }, abstract = {BACKGROUND: In fish, morphological colour changes occur from variations in pigment concentrations and in the morphology, density, and distribution of chromatophores in the skin. However, the underlying mechanisms remain unresolved in most species. Here, we describe the first investigation into the genetic and environmental basis of spot pattern development in one of the world's most studied fishes, the Atlantic salmon. We reared 920 salmon from 64 families of domesticated, F1-hybrid and wild origin in two contrasting environments (Hatchery; tanks for the freshwater stage and sea cages for the marine stage, and River; a natural river for the freshwater stage and tanks for the marine stage). Fish were measured, photographed and spot patterns evaluated.

RESULTS: In the Hatchery experiment, significant but modest differences in spot density were observed among domesticated, F1-hybrid (1.4-fold spottier than domesticated) and wild salmon (1.7-fold spottier than domesticated). A heritability of 6% was calculated for spot density, and a significant QTL on linkage group SSA014 was detected. In the River experiment, significant but modest differences in spot density were also observed among domesticated, F1-hybrid (1.2-fold spottier than domesticated) and wild salmon (1.8-fold spottier than domesticated). Domesticated salmon were sevenfold spottier in the Hatchery vs. River experiment. While different wild populations were used for the two experiments, on average, these were 6.2-fold spottier in the Hatchery vs. River experiment. Fish in the Hatchery experiment displayed scattered to random spot patterns while fish in the River experiment displayed clustered spot patterns.

CONCLUSIONS: These data demonstrate that while genetics plays an underlying role, environmental variation represents the primary determinant of spot pattern development in Atlantic salmon.}, } @article {pmid29649993, year = {2018}, author = {Cornwell, M and Vangala, M and Taing, L and Herbert, Z and Köster, J and Li, B and Sun, H and Li, T and Zhang, J and Qiu, X and Pun, M and Jeselsohn, R and Brown, M and Liu, XS and Long, HW}, title = {VIPER: Visualization Pipeline for RNA-seq, a Snakemake workflow for efficient and complete RNA-seq analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {135}, pmid = {29649993}, issn = {1471-2105}, support = {K08 CA191058/CA/NCI NIH HHS/United States ; U01 CA180980/NH/NIH HHS/United States ; 31329003//National Natural Science Foundation of China/International ; }, mesh = {Base Sequence ; Cluster Analysis ; Down-Regulation/genetics ; Gene Expression Profiling ; Gene Ontology ; High-Throughput Nucleotide Sequencing/*methods ; RNA, Messenger/genetics/metabolism ; Sequence Alignment ; Sequence Analysis, RNA/*methods ; Signal Transduction/genetics ; *Software ; Up-Regulation/genetics ; *Workflow ; }, abstract = {BACKGROUND: RNA sequencing has become a ubiquitous technology used throughout life sciences as an effective method of measuring RNA abundance quantitatively in tissues and cells. The increase in use of RNA-seq technology has led to the continuous development of new tools for every step of analysis from alignment to downstream pathway analysis. However, effectively using these analysis tools in a scalable and reproducible way can be challenging, especially for non-experts.

RESULTS: Using the workflow management system Snakemake we have developed a user friendly, fast, efficient, and comprehensive pipeline for RNA-seq analysis. VIPER (Visualization Pipeline for RNA-seq analysis) is an analysis workflow that combines some of the most popular tools to take RNA-seq analysis from raw sequencing data, through alignment and quality control, into downstream differential expression and pathway analysis. VIPER has been created in a modular fashion to allow for the rapid incorporation of new tools to expand the capabilities. This capacity has already been exploited to include very recently developed tools that explore immune infiltrate and T-cell CDR (Complementarity-Determining Regions) reconstruction abilities. The pipeline has been conveniently packaged such that minimal computational skills are required to download and install the dozens of software packages that VIPER uses.

CONCLUSIONS: VIPER is a comprehensive solution that performs most standard RNA-seq analyses quickly and effectively with a built-in capacity for customization and expansion.}, } @article {pmid29649979, year = {2018}, author = {Jayakodi, M and Choi, BS and Lee, SC and Kim, NH and Park, JY and Jang, W and Lakshmanan, M and Mohan, SVG and Lee, DY and Yang, TJ}, title = {Ginseng Genome Database: an open-access platform for genomics of Panax ginseng.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {62}, pmid = {29649979}, issn = {1471-2229}, support = {PJ01311901, PJ01334605//Next-Generation BioGreen21 Program/ ; }, mesh = {Databases, Genetic ; Gene Expression Regulation, Plant/genetics/physiology ; Gene Ontology ; Genome, Plant/*genetics ; Ginsenosides/metabolism ; Panax/*genetics/*metabolism ; }, abstract = {BACKGROUND: The ginseng (Panax ginseng C.A. Meyer) is a perennial herbaceous plant that has been used in traditional oriental medicine for thousands of years. Ginsenosides, which have significant pharmacological effects on human health, are the foremost bioactive constituents in this plant. Having realized the importance of this plant to humans, an integrated omics resource becomes indispensable to facilitate genomic research, molecular breeding and pharmacological study of this herb.

DESCRIPTION: The first draft genome sequences of P. ginseng cultivar "Chunpoong" were reported recently. Here, using the draft genome, transcriptome, and functional annotation datasets of P. ginseng, we have constructed the Ginseng Genome Database http://ginsengdb.snu.ac.kr /, the first open-access platform to provide comprehensive genomic resources of P. ginseng. The current version of this database provides the most up-to-date draft genome sequence (of approximately 3000 Mbp of scaffold sequences) along with the structural and functional annotations for 59,352 genes and digital expression of genes based on transcriptome data from different tissues, growth stages and treatments. In addition, tools for visualization and the genomic data from various analyses are provided. All data in the database were manually curated and integrated within a user-friendly query page.

CONCLUSION: This database provides valuable resources for a range of research fields related to P. ginseng and other species belonging to the Apiales order as well as for plant research communities in general. Ginseng genome database can be accessed at http://ginsengdb.snu.ac.kr /.}, } @article {pmid29649975, year = {2018}, author = {Uhía, I and Krishnan, N and Robertson, BD}, title = {Characterising resuscitation promoting factor fluorescent-fusions in mycobacteria.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {30}, pmid = {29649975}, issn = {1471-2180}, abstract = {BACKGROUND: Resuscitation promoting factor proteins (Rpfs) are peptidoglycan glycosidases capable of resuscitating dormant mycobacteria, and have been found to play a role in the pathogenesis of tuberculosis. However, the specific roles and localisation of each of the 5 Rpfs in Mycobacterium tuberculosis remain mostly unknown. In this work our aim was to construct fluorescent fusions of M. tuberculosis Rpf proteins as tools to investigate their function.

RESULTS: We found that Rpf-fusions to the fluorescent protein mCherry are functional and able to promote cell growth under different conditions. However, fusions to Enhanced Green Fluorescent Protein (EGFP) were non-functional in the assays used and none were secreted into the extracellular medium, which suggests Rpfs may be secreted via the Sec pathway. No specific cellular localization was observed for either set of fusions using time-lapse video microscopy.

CONCLUSIONS: We present the validation and testing of five M. tuberculosis Rpfs fused to mCherry, which are functional in resuscitation assays, but do not show any specific cellular localisation under the conditions tested. Our results suggest that Rpfs are likely to be secreted via the Sec pathway. We propose that such mCherry fusions will be useful tools for the further study of Rpf localisation, individual expression, and function.}, } @article {pmid29649971, year = {2018}, author = {Ozsoy, MG and Özyer, T and Polat, F and Alhajj, R}, title = {Realizing drug repositioning by adapting a recommendation system to handle the process.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {136}, pmid = {29649971}, issn = {1471-2105}, mesh = {Area Under Curve ; Computational Biology ; Databases as Topic ; Drug Discovery ; *Drug Repositioning ; Humans ; }, abstract = {BACKGROUND: Drug repositioning is the process of identifying new targets for known drugs. It can be used to overcome problems associated with traditional drug discovery by adapting existing drugs to treat new discovered diseases. Thus, it may reduce associated risk, cost and time required to identify and verify new drugs. Nowadays, drug repositioning has received more attention from industry and academia. To tackle this problem, researchers have applied many different computational methods and have used various features of drugs and diseases.

RESULTS: In this study, we contribute to the ongoing research efforts by combining multiple features, namely chemical structures, protein interactions and side-effects to predict new indications of target drugs. To achieve our target, we realize drug repositioning as a recommendation process and this leads to a new perspective in tackling the problem. The utilized recommendation method is based on Pareto dominance and collaborative filtering. It can also integrate multiple data-sources and multiple features. For the computation part, we applied several settings and we compared their performance. Evaluation results show that the proposed method can achieve more concentrated predictions with high precision, where nearly half of the predictions are true.

CONCLUSIONS: Compared to other state of the art methods described in the literature, the proposed method is better at making right predictions by having higher precision. The reported results demonstrate the applicability and effectiveness of recommendation methods for drug repositioning.}, } @article {pmid29649970, year = {2018}, author = {Li, S and Ma, Q and Chen, H and Wang, D and Liu, Y and Wei, X and You, L and Yao, G and Tian, K and Tang, G}, title = {Correction to: Genetic characterization of Bacillus anthracis in Guizhou Province, Southwest of China.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {31}, pmid = {29649970}, issn = {1471-2180}, abstract = {ERRATUM: Upon publication of the original article (1) it was highlighted by the authors that a grant awarded to support the research work of the study was missed in the acknowledgements. It should also be acknowledged that the grant titled "Genotyping and Molecular Epidemiological Characteristic of Bacillus anthracis in Guizhou Province" awarded by the Program of Natural Science Foundation of Guizhou Province (Grant No. Qian Ke He J Word [2015] 2084)also contributed to the resources for this research. This has since been formally noted in this correction article.}, } @article {pmid29649968, year = {2018}, author = {Graziano, M and Benito, R and Planas, JV and Palstra, AP}, title = {Swimming exercise to control precocious maturation in male seabass (Dicentrarchus labrax).}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {10}, pmid = {29649968}, issn = {1471-213X}, support = {0096/06/15/32//AQUAEXCEL/International ; }, abstract = {BACKGROUND: Male European seabass, already predominant (~ 70%) in cultured stocks, show a high incidence (20-30%) of precocious sexual maturation under current aquaculture practices, leading to important economic losses for the industry. In view of the known modulation of reproductive development by swimming exercise in other teleost species, we aimed at investigating the effects of sustained swimming on reproductive development in seabass males during the first year of life in order to determine if swimming could potentially reduce precocious sexual maturation.

METHODS: Pre-pubertal seabass (3.91 ± 0.22 g of body weight (BW)) were subjected to a 10 week swimming regime at their optimal swimming speed (Uopt) in an oval-shaped Brett-type flume or kept at rest during this period. Using Blazka-type swim tunnels, Uopt was determined three times during the course of the experiment: 0.66 m s- 1 at 19 ± 1 g BW, 10.2 ± 0.2 cm of standard length (SL) (week 1); 0.69 m s- 1 at 38 ± 3 g BW, 12.7 ± 0.3 cm SL (week 5), and also 0.69 m s- 1 at 77 ± 7 g BW, 15.7 ± 0.5 cm SL (week 9). Every 2 weeks, size and gonadal weight were monitored in the exercised (N = 15) and non-exercised fish (N = 15). After 10 weeks, exercised and non-exercised males were sampled to determine plasma 11-ketotestosterone levels, testicular mRNA expression levels of genes involved in steroidogenesis and gametogenesis by qPCR, as well as the relative abundance of germ cells representing the different spermatogenic stages by histological examination.

RESULTS: Our results indicate that sustained swimming exercise at Uopt delays testicular development in male European seabass as evidenced by decreased gonado-somatic index, slower progression of testicular development and by reduced mRNA expression levels of follicle stimulating hormone receptor (fshR), 3-beta-hydroxysteroid dehydrogenase (3βhsd), 11-beta hydroxysteroid dehydrogenase (11βhsd), estrogen receptor-beta (erβ2), anti-mullerian hormone (amh), structural maintenance of chromosomes protein 1B (smc1β), inhibin beta A (inhba) and gonado-somal derived factor 1 (gsdf1) in exercised males as compared with the non-exercised males.

CONCLUSIONS: Swimming exercise may represent a natural and non-invasive tool to reduce the incidence of sexually precocious males in seabass aquaculture.}, } @article {pmid29649581, year = {2018}, author = {Tu, N and Yang, M and Liang, D and Zhang, P}, title = {A large-scale phylogeny of Microhylidae inferred from a combined dataset of 121 genes and 427 taxa.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {85-91}, doi = {10.1016/j.ympev.2018.03.036}, pmid = {29649581}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification/*genetics ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; *Genes ; Geography ; Likelihood Functions ; *Phylogeny ; }, abstract = {The phylogenetic relationships of Microhylidae, the third largest family of extant frogs, have been difficult to resolve. In the past decade, large amounts of sequence data have been deposited for almost every microhylid genus, but no study has attempted to combine these data to reconstruct a comprehensive phylogeny for this family. In this study, we sequenced 20 near-complete or partial microhylid mitochondrial genomes and integrated them with all available sequences of Microhylidae from GenBank to construct a supermatrix containing 121 genes (14 mitochondrial and 107 nuclear protein-coding genes). The combined dataset is 112,328 characters long (average sequence data length per species = 7829 bp), includes 427 microhylid taxa, and covers all but three genera of the entire family. This dataset provides strong support for the traditional classification of 11 nominal subfamilies and improves the phylogenetic resolution of the relationships among subfamilies. The African subfamily Phrynomerinae is the sister group of all the other microhylids, and the African subfamily Hoplophryninae is the sister taxon to a clade comprising the remaining 9 subfamilies. At the genus level, our analyses confirm the monophyly of most but not all microhylid genera. In summary, we present a new large-scale phylogeny of microhylid frogs that should be valuable for addressing their classification and for comparative evolutionary studies.}, } @article {pmid29648875, year = {2018}, author = {Mahmoud, SA and Chien, P}, title = {Regulated Proteolysis in Bacteria.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {677-696}, pmid = {29648875}, issn = {1545-4509}, support = {R01 GM111706/GM/NIGMS NIH HHS/United States ; T32 GM008515/GM/NIGMS NIH HHS/United States ; }, abstract = {Regulated proteolysis is a vital process that affects all living things. Bacteria use energy-dependent AAA+ proteases to power degradation of misfolded and native regulatory proteins. Given that proteolysis is an irreversible event, specificity and selectivity in degrading substrates are key. Specificity is often augmented through the use of adaptors that modify the inherent specificity of the proteolytic machinery. Regulated protein degradation is intricately linked to quality control, cell-cycle progression, and physiological transitions. In this review, we highlight recent work that has shed light on our understanding of regulated proteolysis in bacteria. We discuss the role AAA+ proteases play during balanced growth as well as how these proteases are deployed during changes in growth. We present examples of how protease selectivity can be controlled in increasingly complex ways. Finally, we describe how coupling a core recognition determinant to one or more modifying agents is a general theme for regulated protein degradation.}, } @article {pmid29648587, year = {2018}, author = {Salami, SA and Valenti, B and Bella, M and O'Grady, MN and Luciano, G and Kerry, JP and Jones, E and Priolo, A and Newbold, CJ}, title = {Characterisation of the ruminal fermentation and microbiome in lambs supplemented with hydrolysable and condensed tannins.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy061}, pmid = {29648587}, issn = {1574-6941}, abstract = {This study characterised the response of ruminal fermentation and the rumen microbiome in lambs fed commercial vegetal sources of hydrolysable tannins (HT) and condensed tannins (CT). Forty-four lambs (19.56 ± 2.06 kg) were randomly assigned to either a concentrate diet (CON, n = 8) or CON supplemented with 4% of two HT [chestnut (Castanea sativa, HT-c) and tara (Caesalpinia spinosa, HT-t)] and CT [mimosa (Acacia negra, CT-m) and gambier (Uncaria gambir, CT-g)] extracts (all, n = 9) for 75 days pre-slaughter. Tannin supplementation did not influence ruminal fermentation traits. Quantitative PCR demonstrated that tannins did not affect the absolute abundance of ruminal bacteria or fungi. However, CT-m (-12.8%) and CT-g (-11.5%) significantly reduced the abundance of methanogens, while HT-t (-20.7%) and CT-g (-20.8%) inhibited protozoal abundance. Ribosomal amplicon sequencing revealed that tannins caused changes in the phylogenetic structure of the bacterial and methanogen communities. Tannins inhibited the fibrolytic bacterium, Fibrobacter and tended to suppress the methanogen genus, Methanosphaera. Results demonstrated that both HT and CT sources could impact the ruminal microbiome when supplemented at 4% inclusion level. HT-t, CT-m and CT-g extracts displayed specific antimicrobial activity against methanogens and protozoa without compromising ruminal fermentation in a long-term feeding trial.}, } @article {pmid29648528, year = {2018}, author = {McFrederick, QS and Vuong, HQ and Rothman, JA}, title = {Lactobacillus micheneri sp. nov., Lactobacillus timberlakei sp. nov. and Lactobacillus quenuiae sp. nov., lactic acid bacteria isolated from wild bees and flowers.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1879-1884}, doi = {10.1099/ijsem.0.002758}, pmid = {29648528}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Bees/*microbiology ; California ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flowers/*microbiology ; Lactobacillus/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Gram-stain-positive, rod-shaped, non-spore forming bacteria have been isolated from flowers and the guts of adult wild bees in the families Megachilidae and Halictidae. Phylogenetic analysis of the 16S rRNA gene indicated that these bacteria belong to the genus Lactobacillus, and are most closely related to the honey-bee associated bacteria Lactobacillus kunkeei (97.0 % sequence similarity) and Lactobacillus apinorum (97.0 % sequence similarity). Phylogenetic analyses of 16S rRNA genes and six single-copy protein coding genes, in situ and in silico DNA-DNA hybridization, and fatty-acid profiling differentiates the newly isolated bacteria as three novel Lactobacillus species: Lactobacillus micheneri sp. nov. with the type strain Hlig3T (=DSM 104126T,=NRRL B-65473T), Lactobacillus timberlakei with the type strain HV_12T (=DSM 104128T,=NRRL B-65472T), and Lactobacillus quenuiae sp. nov. with the type strain HV_6T (=DSM 104127T,=NRRL B-65474T).}, } @article {pmid29648527, year = {2018}, author = {Mo, P and Zhao, J and Li, K and Tang, X and Gao, J}, title = {Streptomyces manganisoli sp. nov., a novel actinomycete isolated from manganese-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1890-1895}, doi = {10.1099/ijsem.0.002762}, pmid = {29648527}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Manganese ; Mining ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Soil Pollutants ; Streptomyces/*classification/genetics/isolation & purification ; Vitamin K 2/chemistry ; }, abstract = {A novel actinomycete isolate, designated strain MK44T, was isolated from a Manganese-polluted soil sample collected near Xiangtan Manganese Mine, South Central China and subjected to a polyphasic taxonomic characterization. Comparison of 16S rRNA gene sequences showed that strain MK44T was a member of the genus Streptomyces and most closely related to Streptomyces specialis JCM 16611T (97.9 %) and Streptomyces mayteni JCM 16957T (97.4 %). The DNA-DNA relatedness between strain MK44T and the above two related type species were 30.9±0.3 and 29.9±3.5 %, respectively, values which are far lower than the 70 % threshold for the delineation of a novel prokaryotic species. Furthermore, the results of physiological, biochemical and chemotaxonomic tests allowed further phenotypic differentiation. Therefore, it is concluded that strain MK44T represents a novel species of the genus Streptomyces, for which the name Streptomyces manganisoli sp. nov. is proposed. The type strain is MK44T (=GDMCC 4.137T=KCTC 39920T).}, } @article {pmid29648526, year = {2018}, author = {Dahal, RH and Kim, J}, title = {Fluviicola kyonggii sp. nov., a bacterium isolated from forest soil and emended description of the genus Fluviicola.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1885-1889}, doi = {10.1099/ijsem.0.002759}, pmid = {29648526}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; *Forests ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel bacterium, designated strain CA-1T, was isolated from forest soil in Kyonggi University. Cells were strictly aerobic, Gram-stain-negative, catalase-positive, oxidase-negative, non-motile, non-spore-forming, rod-shaped and red-orange-pigmented. Strain CA-1T hydrolysed casein and DNA. It was able to grow at 15-37 °C, pH 5.5-9.0 and at 0-2 % (w/v) NaCl concentration. Flexirubin-type pigments were present. Phylogenetic analysis based on its 16S rRNA gene sequence indicated that strain CA-1T formed a lineage within the family Crocinitomicaceae of the phylum Bacteroidetes that was distinct from Fluviicola hefeinensis MYL-8T (96.8 % sequence similarity) and Fluviicola taffensis DSM 16823T (96.1 %). Strain CA-1T contained menaquinone-6 as a sole respiratory quinone. The major polar lipids were phosphatidylethanolamine, unidentified aminolipids, an unidentified aminophospholipid and an unidentified lipid. The major cellular fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, C15 : 0 2-OH, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and iso-C15 : 1 G. The DNA G+C content of strain CA-1T was 44.1 mol%. The polyphasic characterization revealed that strain CA-1T represents a novel species in the genus Fluviicola, for which the name Fluviicola kyonggii sp. nov. is proposed. The type strain is CA-1T (=KEMB 9005-526T=KACC 19148T=NBRC 112684T).}, } @article {pmid29645092, year = {2018}, author = {Petersen, KB and Burd, M}, title = {The adaptive value of heterospory: Evidence from Selaginella.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1080-1091}, doi = {10.1111/evo.13484}, pmid = {29645092}, issn = {1558-5646}, abstract = {Heterospory was a pivotal evolutionary innovation for land plants, but it has never been clear why it evolved. We used the geographic distributions of 114 species of the heterosporous lycophyte Selaginella to explore the functional ecology of microspore and megaspore size, traits that would be correlated with many aspects of a species' regeneration niche. We characterized habitats at a global scale using leaf area index (LAI), a measure of foliage density and thus shading, and net primary productivity (NPP), a measure of growth potential. Microspore size tends to decrease as habitat LAI and NPP increase, a trend that could be related to desiccation resistance or to filtration of wind-borne particles by leaf surfaces. Megaspore size tends to increase among species that inhabit regions of high LAI, but there is an important interaction with NPP. This geographical pattern suggests that larger megaspores provide an establishment advantage in shaded habitats, although in open habitats, where light is less limiting, higher productivity of the environment seems to give an advantage to species with smaller megaspores. These results support previous theoretical arguments that heterospory was originally an adaptation to the increasing height and density of Devonian vegetative canopies that accompanied the diversification of vascular plants with leaves.}, } @article {pmid29645091, year = {2018}, author = {Neiman, M and Meirmans, PG and Schwander, T and Meirmans, S}, title = {Sex in the wild: How and why field-based studies contribute to solving the problem of sex.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1194-1203}, doi = {10.1111/evo.13485}, pmid = {29645091}, issn = {1558-5646}, abstract = {Why and how sexual reproduction is maintained in natural populations, the so-called "queen of problems," is a key unanswered question in evolutionary biology. Recent efforts to solve the problem of sex have often emphasized results generated from laboratory settings. Here, we use a survey of representative "sex in the wild" literature to review and synthesize the outcomes of empirical studies focused on natural populations. Especially notable results included relatively strong support for mechanisms involving niche differentiation and a near absence of attention to adaptive evolution. Support for a major role of parasites is largely confined to a single study system, and only three systems contribute most of the support for mutation accumulation hypotheses. This evidence for taxon specificity suggests that outcomes of particular studies should not be more broadly extrapolated without extreme caution. We conclude by suggesting steps forward, highlighting tests of niche differentiation mechanisms in both laboratory and nature, and empirical evaluation of adaptive evolution-focused hypotheses in the wild. We also emphasize the value of leveraging the growing body of genomic resources for nonmodel taxa to address whether the clearance of harmful mutations and spread of beneficial variants in natural populations proceeds as expected under various hypotheses for sex.}, } @article {pmid29645009, year = {2017}, author = {Lea, AJ and Tung, J and Archie, EA and Alberts, SC}, title = {Developmental plasticity research in evolution and human health: Response to commentaries.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {201-205}, pmid = {29645009}, issn = {2050-6201}, } @article {pmid29644624, year = {2018}, author = {Rougemont, Q and Bernatchez, L}, title = {The demographic history of Atlantic salmon (Salmo salar) across its distribution range reconstructed from approximate Bayesian computations.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1261-1277}, doi = {10.1111/evo.13486}, pmid = {29644624}, issn = {1558-5646}, abstract = {Understanding the dual roles of demographic and selective processes in the buildup of population divergence is one of the most challenging tasks in evolutionary biology. Here, we investigated the demographic history of Atlantic salmon across the entire species range using 2035 anadromous individuals from North America and Eurasia. By combining results from admixture graphs, geo-genetic maps, and an Approximate Bayesian Computation (ABC) framework, we validated previous hypotheses pertaining to secondary contact between European and Northern American populations, but also identified secondary contacts in European populations from different glacial refugia. We further identified the major sources of admixture from the southern range of North America into more northern populations along with a strong signal of secondary gene flow between genetic regional groups. We hypothesize that these patterns reflect the spatial redistribution of ancestral variation across the entire North American range. Results also support a role for linked selection and differential introgression that likely played an underappreciated role in shaping the genomic landscape of species in the Northern hemisphere. We conclude that studies between partially isolated populations should systematically include heterogeneity in selective and introgressive effects among loci to perform more rigorous demographic inferences of the divergence process.}, } @article {pmid29644076, year = {2018}, author = {Mainieri, A and Haig, D}, title = {Lost in translation: The 3'-UTR of IGF1R as an ancient long noncoding RNA.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {82-91}, pmid = {29644076}, issn = {2050-6201}, abstract = {Background and objectives: The insulin-like growth factor (IGF) signaling system is a major arena of intragenomic conflict over embryonic growth between imprinted genes of maternal and paternal origin and the IGF type 1 receptor (IGF1R) promotes proliferation of many human cancers. The 3'-untranslated region (3'-UTR) of the mouse Igf1r mRNA is targeted by miR-675-3p derived from the imprinted H19 long noncoding RNA. We undertook a comparative sequence analysis of vertebrate IGF1R 3'-UTRs to determine the evolutionary history of miR-675 target sequences and to identify conserved features that are likely to be involved in post-transcriptional regulation of IGF1R translation.

Methodology: Sequences of IGF1R 3'-UTRs were obtained from public databases and analyzed using publicly available algorithms.

Results: A very long 3'-UTR is a conserved feature of vertebrate IGF1R mRNAs. We found that some ancient microRNAs, such as let-7 and mir-182, have predicted binding sites that are conserved between cartilaginous fish and mammals. One very conserved region is targeted by multiple, maternally expressed imprinted microRNAs that appear to have evolved more recently than the targeted sequences.

Conclusions and implications: The conserved structures we identify in the IGF1R 3'-UTR are strong candidates for regulating cell proliferation during development and carcinogenesis. These conserved structures are now targeted by multiple imprinted microRNAs. These observations emphasize the central importance of IGF signaling pathways in the mediation of intragenomic conflicts over embryonic growth and identify possible targets for therapeutic interventions in cancer.}, } @article {pmid29643514, year = {2018}, author = {Du Toit, A}, title = {Blasting through cells.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {330-331}, doi = {10.1038/s41579-018-0009-0}, pmid = {29643514}, issn = {1740-1534}, } @article {pmid29643513, year = {2018}, author = {Wrighton, K}, title = {Finding IRESs in mycoviruses.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {330}, doi = {10.1038/s41579-018-0011-6}, pmid = {29643513}, issn = {1740-1534}, } @article {pmid29643512, year = {2018}, author = {Wendeln, AC and Degenhardt, K and Kaurani, L and Gertig, M and Ulas, T and Jain, G and Wagner, J and Häsler, LM and Wild, K and Skodras, A and Blank, T and Staszewski, O and Datta, M and Centeno, TP and Capece, V and Islam, MR and Kerimoglu, C and Staufenbiel, M and Schultze, JL and Beyer, M and Prinz, M and Jucker, M and Fischer, A and Neher, JJ}, title = {Innate immune memory in the brain shapes neurological disease hallmarks.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {332-338}, pmid = {29643512}, issn = {1476-4687}, support = {648898//European Research Council/International ; }, mesh = {Alzheimer Disease/immunology/pathology ; Amyloidosis/immunology/pathology ; Animals ; Brain/*immunology/*pathology ; Disease Models, Animal ; Epigenesis, Genetic ; Female ; Gene Expression Regulation/immunology ; Humans ; Immune Tolerance ; *Immunity, Innate ; *Immunologic Memory ; Inflammation/genetics/immunology ; Male ; Mice ; Microglia/immunology/metabolism ; Nervous System Diseases/*immunology/*pathology ; Stroke/immunology/pathology ; }, abstract = {Innate immune memory is a vital mechanism of myeloid cell plasticity that occurs in response to environmental stimuli and alters subsequent immune responses. Two types of immunological imprinting can be distinguished-training and tolerance. These are epigenetically mediated and enhance or suppress subsequent inflammation, respectively. Whether immune memory occurs in tissue-resident macrophages in vivo and how it may affect pathology remains largely unknown. Here we demonstrate that peripherally applied inflammatory stimuli induce acute immune training and tolerance in the brain and lead to differential epigenetic reprogramming of brain-resident macrophages (microglia) that persists for at least six months. Strikingly, in a mouse model of Alzheimer's pathology, immune training exacerbates cerebral β-amyloidosis and immune tolerance alleviates it; similarly, peripheral immune stimulation modifies pathological features after stroke. Our results identify immune memory in the brain as an important modifier of neuropathology.}, } @article {pmid29643511, year = {2018}, author = {Pao, KC and Wood, NT and Knebel, A and Rafie, K and Stanley, M and Mabbitt, PD and Sundaramoorthy, R and Hofmann, K and van Aalten, DMF and Virdee, S}, title = {Activity-based E3 ligase profiling uncovers an E3 ligase with esterification activity.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {381-385}, doi = {10.1038/s41586-018-0026-1}, pmid = {29643511}, issn = {1476-4687}, support = {MC_UU_12016/8//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Adaptor Proteins, Signal Transducing/*chemistry/*metabolism ; *Biocatalysis ; Cell Line, Tumor ; Crystallography, X-Ray ; Cysteine/metabolism ; Esterification ; HEK293 Cells ; Humans ; Lysine/metabolism ; Models, Molecular ; Protein Domains ; Proteomics ; Serine/metabolism ; Substrate Specificity ; Threonine/metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/*chemistry/*metabolism ; Ubiquitination ; }, abstract = {Ubiquitination is initiated by transfer of ubiquitin (Ub) from a ubiquitin-activating enzyme (E1) to a ubiquitin-conjugating enzyme (E2), producing a covalently linked intermediate (E2-Ub) 1 . Ubiquitin ligases (E3s) of the 'really interesting new gene' (RING) class recruit E2-Ub via their RING domain and then mediate direct transfer of ubiquitin to substrates 2 . By contrast, 'homologous to E6-AP carboxy terminus' (HECT) E3 ligases undergo a catalytic cysteine-dependent transthiolation reaction with E2-Ub, forming a covalent E3-Ub intermediate3,4. Additionally, RING-between-RING (RBR) E3 ligases have a canonical RING domain that is linked to an ancillary domain. This ancillary domain contains a catalytic cysteine that enables a hybrid RING-HECT mechanism 5 . Ubiquitination is typically considered a post-translational modification of lysine residues, as there are no known human E3 ligases with non-lysine activity. Here we perform activity-based protein profiling of HECT or RBR-like E3 ligases and identify the neuron-associated E3 ligase MYCBP2 (also known as PHR1) as the apparent single member of a class of RING-linked E3 ligase with esterification activity and intrinsic selectivity for threonine over serine. MYCBP2 contains two essential catalytic cysteine residues that relay ubiquitin to its substrate via thioester intermediates. Crystallographic characterization of this class of E3 ligase, which we designate RING-Cys-relay (RCR), provides insights into its mechanism and threonine selectivity. These findings implicate non-lysine ubiquitination in cellular regulation of higher eukaryotes and suggest that E3 enzymes have an unappreciated mechanistic diversity.}, } @article {pmid29643510, year = {2018}, author = {Roerink, SF and Sasaki, N and Lee-Six, H and Young, MD and Alexandrov, LB and Behjati, S and Mitchell, TJ and Grossmann, S and Lightfoot, H and Egan, DA and Pronk, A and Smakman, N and van Gorp, J and Anderson, E and Gamble, SJ and Alder, C and van de Wetering, M and Campbell, PJ and Stratton, MR and Clevers, H}, title = {Intra-tumour diversification in colorectal cancer at the single-cell level.}, journal = {Nature}, volume = {556}, number = {7702}, pages = {457-462}, doi = {10.1038/s41586-018-0024-3}, pmid = {29643510}, issn = {1476-4687}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Proliferation ; Clone Cells/*drug effects/metabolism/pathology ; Colorectal Neoplasms/drug therapy/*genetics/metabolism/*pathology ; DNA Methylation ; DNA Mutational Analysis ; *Evolution, Molecular ; Gene Expression Regulation, Neoplastic ; Humans ; Intestinal Mucosa/metabolism ; Intestines/cytology/drug effects/pathology ; *Mutation ; Mutation Rate ; Organoids/cytology/drug effects/metabolism/pathology ; *Single-Cell Analysis ; Transcriptome ; }, abstract = {Every cancer originates from a single cell. During expansion of the neoplastic cell population, individual cells acquire genetic and phenotypic differences from each other. Here, to investigate the nature and extent of intra-tumour diversification, we characterized organoids derived from multiple single cells from three colorectal cancers as well as from adjacent normal intestinal crypts. Colorectal cancer cells showed extensive mutational diversification and carried several times more somatic mutations than normal colorectal cells. Most mutations were acquired during the final dominant clonal expansion of the cancer and resulted from mutational processes that are absent from normal colorectal cells. Intra-tumour diversification of DNA methylation and transcriptome states also occurred; these alterations were cell-autonomous, stable, and followed the phylogenetic tree of each cancer. There were marked differences in responses to anticancer drugs between even closely related cells of the same tumour. The results indicate that colorectal cancer cells experience substantial increases in somatic mutation rate compared to normal colorectal cells, and that genetic diversification of each cancer is accompanied by pervasive, stable and inherited differences in the biological states of individual cancer cells.}, } @article {pmid29643509, year = {2018}, author = {Eustermann, S and Schall, K and Kostrewa, D and Lakomek, K and Strauss, M and Moldt, M and Hopfner, KP}, title = {Structural basis for ATP-dependent chromatin remodelling by the INO80 complex.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {386-390}, pmid = {29643509}, issn = {1476-4687}, support = {322869//European Research Council/International ; }, mesh = {Adenosine Triphosphate/*metabolism ; Amino Acid Sequence ; Chaetomium/*enzymology ; *Chromatin Assembly and Disassembly ; Chromosomal Proteins, Non-Histone/chemistry/metabolism ; *Cryoelectron Microscopy ; DNA/chemistry/metabolism/ultrastructure ; DNA Helicases/chemistry/metabolism/*ultrastructure ; Fungal Proteins ; Histones/chemistry/metabolism/ultrastructure ; Humans ; Models, Molecular ; Multiprotein Complexes/chemistry/metabolism/*ultrastructure ; Nucleosomes/chemistry/*metabolism/ultrastructure ; Protein Binding ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; Structure-Activity Relationship ; }, abstract = {In the eukaryotic nucleus, DNA is packaged in the form of nucleosomes, each of which comprises about 147 base pairs of DNA wrapped around a histone protein octamer. The position and histone composition of nucleosomes is governed by ATP-dependent chromatin remodellers1-3 such as the 15-subunit INO80 complex 4 . INO80 regulates gene expression, DNA repair and replication by sliding nucleosomes, the exchange of histone H2A.Z with H2A, and the positioning of + 1 and -1 nucleosomes at promoter DNA5-8. The structures and mechanisms of these remodelling reactions are currently unknown. Here we report the cryo-electron microscopy structure of the evolutionarily conserved core of the INO80 complex from the fungus Chaetomium thermophilum bound to a nucleosome, at a global resolution of 4.3 Å and with major parts at 3.7 Å. The INO80 core cradles one entire gyre of the nucleosome through multivalent DNA and histone contacts. An Rvb1/Rvb2 AAA+ ATPase heterohexamer is an assembly scaffold for the complex and acts as a 'stator' for the motor and nucleosome-gripping subunits. The Swi2/Snf2 ATPase motor binds to nucleosomal DNA at superhelical location -6, unwraps approximately 15 base pairs, disrupts the H2A-DNA contacts and is poised to pump entry DNA into the nucleosome. Arp5 and Ies6 bind superhelical locations -2 and -3 to act as a counter grip for the motor, on the other side of the H2A-H2B dimer. The Arp5 insertion domain forms a grappler element that binds the nucleosome dyad, connects the Arp5 actin-fold and entry DNA over a distance of about 90 Å and packs against histone H2A-H2B near the 'acidic patch'. Our structure together with biochemical data 8 suggests a unified mechanism for nucleosome sliding and histone editing by INO80. The motor is part of a macromolecular ratchet, persistently pumping entry DNA across the H2A-H2B dimer against the Arp5 grip until a large nucleosome translocation step occurs. The transient exposure of H2A-H2B by motor activity as well as differential recognition of H2A.Z and H2A may regulate histone exchange.}, } @article {pmid29643508, year = {2018}, author = {Johnson, MB and Sun, X and Kodani, A and Borges-Monroy, R and Girskis, KM and Ryu, SC and Wang, PP and Patel, K and Gonzalez, DM and Woo, YM and Yan, Z and Liang, B and Smith, RS and Chatterjee, M and Coman, D and Papademetris, X and Staib, LH and Hyder, F and Mandeville, JB and Grant, PE and Im, K and Kwak, H and Engelhardt, JF and Walsh, CA and Bae, BI}, title = {Aspm knockout ferret reveals an evolutionary mechanism governing cerebral cortical size.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {370-375}, pmid = {29643508}, issn = {1476-4687}, support = {R01 NS032457/NS/NINDS NIH HHS/United States ; R24 MH114805/MH/NIMH NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; P30 NS052519/NS/NINDS NIH HHS/United States ; F32 NS100338/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 MH067528/MH/NIMH NIH HHS/United States ; R01 EB017337/EB/NIBIB NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 NS035129/NS/NINDS NIH HHS/United States ; R21 NS091865/NS/NINDS NIH HHS/United States ; R24 HL123482/HL/NHLBI NIH HHS/United States ; R21 HD083956/HD/NICHD NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; *Biological Evolution ; Calmodulin-Binding Proteins/deficiency/metabolism ; Centrosome/metabolism ; Cerebral Cortex/*anatomy & histology/*metabolism/pathology ; Disease Models, Animal ; Female ; *Ferrets/anatomy & histology/genetics ; *Gene Deletion ; Gene Editing ; Gene Expression Regulation, Developmental ; Gene Knockout Techniques ; Germ-Line Mutation ; Humans ; Male ; Mice ; Microcephaly/*genetics/*pathology ; Nerve Tissue Proteins/chemistry/*deficiency/genetics/metabolism ; Neural Stem Cells/metabolism/pathology ; Organ Size ; Transcription, Genetic ; }, abstract = {The human cerebral cortex is distinguished by its large size and abundant gyrification, or folding. However, the evolutionary mechanisms that drive cortical size and structure are unknown. Although genes that are essential for cortical developmental expansion have been identified from the genetics of human primary microcephaly (a disorder associated with reduced brain size and intellectual disability) 1 , studies of these genes in mice, which have a smooth cortex that is one thousand times smaller than the cortex of humans, have provided limited insight. Mutations in abnormal spindle-like microcephaly-associated (ASPM), the most common recessive microcephaly gene, reduce cortical volume by at least 50% in humans2-4, but have little effect on the brains of mice5-9; this probably reflects evolutionarily divergent functions of ASPM10,11. Here we used genome editing to create a germline knockout of Aspm in the ferret (Mustela putorius furo), a species with a larger, gyrified cortex and greater neural progenitor cell diversity12-14 than mice, and closer protein sequence homology to the human ASPM protein. Aspm knockout ferrets exhibit severe microcephaly (25-40% decreases in brain weight), reflecting reduced cortical surface area without significant change in cortical thickness, as has been found in human patients3,4, suggesting that loss of 'cortical units' has occurred. The cortex of fetal Aspm knockout ferrets displays a very large premature displacement of ventricular radial glial cells to the outer subventricular zone, where many resemble outer radial glia, a subtype of neural progenitor cells that are essentially absent in mice and have been implicated in cerebral cortical expansion in primates12-16. These data suggest an evolutionary mechanism by which ASPM regulates cortical expansion by controlling the affinity of ventricular radial glial cells for the ventricular surface, thus modulating the ratio of ventricular radial glial cells, the most undifferentiated cell type, to outer radial glia, a more differentiated progenitor.}, } @article {pmid29643507, year = {2018}, author = {Liakath-Ali, K and Mills, EW and Sequeira, I and Lichtenberger, BM and Pisco, AO and Sipilä, KH and Mishra, A and Yoshikawa, H and Wu, CC and Ly, T and Lamond, AI and Adham, IM and Green, R and Watt, FM}, title = {An evolutionarily conserved ribosome-rescue pathway maintains epidermal homeostasis.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {376-380}, doi = {10.1038/s41586-018-0032-3}, pmid = {29643507}, issn = {1476-4687}, mesh = {Animals ; *Biological Evolution ; Cell Cycle Proteins/deficiency/genetics ; Cell Differentiation ; Cell Proliferation ; Disease Progression ; Epidermal Cells ; Epidermis/*metabolism/pathology ; Female ; *Homeostasis/genetics ; Male ; Membrane Glycoproteins/metabolism ; Mice ; Microfilament Proteins/deficiency/genetics ; Mutation ; Nerve Tissue Proteins/metabolism ; Phenotype ; Protein Biosynthesis ; RNA, Messenger/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Ribosomes/*metabolism ; Stem Cells/cytology/*metabolism ; TOR Serine-Threonine Kinases/antagonists & inhibitors/metabolism ; }, abstract = {Ribosome-associated mRNA quality control mechanisms ensure the fidelity of protein translation1,2. Although these mechanisms have been extensively studied in yeast, little is known about their role in mammalian tissues, despite emerging evidence that stem cell fate is controlled by translational mechanisms3,4. One evolutionarily conserved component of the quality control machinery, Dom34 (in higher eukaryotes known as Pelota (Pelo)), rescues stalled ribosomes 5 . Here we show that Pelo is required for mammalian epidermal homeostasis. Conditional deletion of Pelo in mouse epidermal stem cells that express Lrig1 results in hyperproliferation and abnormal differentiation of these cells. By contrast, deletion of Pelo in Lgr5-expressing stem cells has no effect and deletion in Lgr6-expressing stem cells induces only a mild phenotype. Loss of Pelo results in accumulation of short ribosome footprints and global upregulation of translation, rather than affecting the expression of specific genes. Translational inhibition by rapamycin-mediated downregulation of mTOR (mechanistic target of rapamycin kinase) rescues the epidermal phenotype. Our study reveals that the ribosome-rescue machinery is important for mammalian tissue homeostasis and that it has specific effects on different stem cell populations.}, } @article {pmid29643506, year = {2018}, author = {Ayala, R and Willhoft, O and Aramayo, RJ and Wilkinson, M and McCormack, EA and Ocloo, L and Wigley, DB and Zhang, X}, title = {Structure and regulation of the human INO80-nucleosome complex.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {391-395}, pmid = {29643506}, issn = {1476-4687}, support = {098412//Wellcome Trust/United Kingdom ; 091093//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; 12799//Cancer Research UK/United Kingdom ; A12799//Cancer Research UK/United Kingdom ; 209327//Wellcome Trust/United Kingdom ; }, mesh = {Actins/chemistry/metabolism ; DNA Helicases/*chemistry/*metabolism ; DNA-Binding Proteins/chemistry/metabolism ; Histones/chemistry/metabolism ; Humans ; Microfilament Proteins/chemistry/metabolism ; Models, Molecular ; Multiprotein Complexes/chemistry/metabolism ; Nucleosomes/*chemistry/*metabolism ; Protein Domains ; Ubiquitin-Protein Ligases/chemistry/metabolism ; }, abstract = {Access to DNA within nucleosomes is required for a variety of processes in cells including transcription, replication and repair. Consequently, cells encode multiple systems that remodel nucleosomes. These complexes can be simple, involving one or a few protein subunits, or more complicated multi-subunit machines 1 . Biochemical studies2-4 have placed the motor domains of several chromatin remodellers in the superhelical location 2 region of the nucleosome. Structural studies of yeast Chd1 and Snf2-a subunit in the complex with the capacity to remodel the structure of chromatin (RSC)-in complex with nucleosomes5-7 have provided insights into the basic mechanism of nucleosome sliding performed by these complexes. However, how larger, multi-subunit remodelling complexes such as INO80 interact with nucleosomes and how remodellers carry out functions such as nucleosome sliding 8 , histone exchange 9 and nucleosome spacing10-12 remain poorly understood. Although some remodellers work as monomers 13 , others work as highly cooperative dimers11, 14, 15. Here we present the structure of the human INO80 chromatin remodeller with a bound nucleosome, which reveals that INO80 interacts with nucleosomes in a previously undescribed manner: the motor domains are located on the DNA at the entry point to the nucleosome, rather than at superhelical location 2. The ARP5-IES6 module of INO80 makes additional contacts on the opposite side of the nucleosome. This arrangement enables the histone H3 tails of the nucleosome to have a role in the regulation of the activities of the INO80 motor domain-unlike in other characterized remodellers, for which H4 tails have been shown to regulate the motor domains.}, } @article {pmid29643505, year = {2018}, author = {Martins, MJF and Puckett, TM and Lockwood, R and Swaddle, JP and Hunt, G}, title = {High male sexual investment as a driver of extinction in fossil ostracods.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {366-369}, doi = {10.1038/s41586-018-0020-7}, pmid = {29643505}, issn = {1476-4687}, mesh = {Adaptation, Physiological ; Animals ; Body Size ; Crustacea/anatomy & histology/classification/*physiology ; *Extinction, Biological ; Female ; *Fossils ; Male ; *Mating Preference, Animal ; Models, Biological ; Reproduction ; Risk Factors ; *Selection, Genetic ; Sex Characteristics ; }, abstract = {Sexual selection favours traits that confer advantages in the competition for mates. In many cases, such traits are costly to produce and maintain, because the costs help to enforce the honesty of these signals and cues 1 . Some evolutionary models predict that sexual selection also produces costs at the population level, which could limit the ability of populations to adapt to changing conditions and thus increase the risk of extinction2-4. Other models, however, suggest that sexual selection should increase rates of adaptation and enhance the removal of deleterious mutations, thus protecting populations against extinction3, 5, 6. Resolving the conflict between these models is not only important for explaining the history of biodiversity, but also relevant to understanding the mechanisms of the current biodiversity crisis. Previous attempts to test the conflicting predictions produced by these models have been limited to extant species and have thus relied on indirect proxies for species extinction. Here we use the informative fossil record of cytheroid ostracods-small, bivalved crustaceans with sexually dimorphic carapaces-to test how sexual selection relates to actual species extinction. We show that species with more pronounced sexual dimorphism, indicating the highest levels of male investment in reproduction, had estimated extinction rates that were ten times higher than those of the species with the lowest investment. These results indicate that sexual selection can be a substantial risk factor for extinction.}, } @article {pmid29643504, year = {2018}, author = {Peter, J and De Chiara, M and Friedrich, A and Yue, JX and Pflieger, D and Bergström, A and Sigwalt, A and Barre, B and Freel, K and Llored, A and Cruaud, C and Labadie, K and Aury, JM and Istace, B and Lebrigand, K and Barbry, P and Engelen, S and Lemainque, A and Wincker, P and Liti, G and Schacherer, J}, title = {Genome evolution across 1,011 Saccharomyces cerevisiae isolates.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {339-344}, doi = {10.1038/s41586-018-0030-5}, pmid = {29643504}, issn = {1476-4687}, support = {R01 GM101091-01/NH/NIH HHS/United States ; }, mesh = {Alleles ; Aneuploidy ; China ; DNA Copy Number Variations ; *Evolution, Molecular ; Genetic Association Studies ; *Genetic Variation ; Genome, Fungal/*genetics ; Genome-Wide Association Study ; Genomics ; Loss of Heterozygosity ; Phenotype ; Phylogeny ; Phylogeography ; Ploidies ; Polymorphism, Single Nucleotide ; Saccharomyces cerevisiae/*classification/*genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {Large-scale population genomic surveys are essential to explore the phenotypic diversity of natural populations. Here we report the whole-genome sequencing and phenotyping of 1,011 Saccharomyces cerevisiae isolates, which together provide an accurate evolutionary picture of the genomic variants that shape the species-wide phenotypic landscape of this yeast. Genomic analyses support a single 'out-of-China' origin for this species, followed by several independent domestication events. Although domesticated isolates exhibit high variation in ploidy, aneuploidy and genome content, genome evolution in wild isolates is mainly driven by the accumulation of single nucleotide polymorphisms. A common feature is the extensive loss of heterozygosity, which represents an essential source of inter-individual variation in this mainly asexual species. Most of the single nucleotide polymorphisms, including experimentally identified functional polymorphisms, are present at very low frequencies. The largest numbers of variants identified by genome-wide association are copy-number changes, which have a greater phenotypic effect than do single nucleotide polymorphisms. This resource will guide future population genomics and genotype-phenotype studies in this classic model system.}, } @article {pmid29643503, year = {2018}, author = {Kohl, J and Babayan, BM and Rubinstein, ND and Autry, AE and Marin-Rodriguez, B and Kapoor, V and Miyamishi, K and Zweifel, LS and Luo, L and Uchida, N and Dulac, C}, title = {Functional circuit architecture underlying parental behaviour.}, journal = {Nature}, volume = {556}, number = {7701}, pages = {326-331}, pmid = {29643503}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; K99 HD085188/HD/NICHD NIH HHS/United States ; R01 HD082131/HD/NICHD NIH HHS/United States ; 106096//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Female ; Galanin/metabolism ; Hormones/metabolism ; Logic ; Male ; Maternal Behavior/*physiology/*psychology ; Mice ; Motivation ; *Neural Pathways ; Neurons/metabolism ; Optogenetics ; Parenting ; Paternal Behavior/*physiology/*psychology ; Preoptic Area/cytology/physiology ; Reproduction/physiology ; Sex Characteristics ; *Social Behavior ; }, abstract = {Parenting is essential for the survival and wellbeing of mammalian offspring. However, we lack a circuit-level understanding of how distinct components of this behaviour are coordinated. Here we investigate how galanin-expressing neurons in the medial preoptic area (MPOAGal) of the hypothalamus coordinate motor, motivational, hormonal and social aspects of parenting in mice. These neurons integrate inputs from a large number of brain areas and the activation of these inputs depends on the animal's sex and reproductive state. Subsets of MPOAGal neurons form discrete pools that are defined by their projection sites. While the MPOAGal population is active during all episodes of parental behaviour, individual pools are tuned to characteristic aspects of parenting. Optogenetic manipulation of MPOAGal projections mirrors this specificity, affecting discrete parenting components. This functional organization, reminiscent of the control of motor sequences by pools of spinal cord neurons, provides a new model for how discrete elements of a social behaviour are generated at the circuit level.}, } @article {pmid29643499, year = {2018}, author = {}, title = {Suspected chemical attack, opioid-crisis cash and nuclear-fusion facility.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {154-155}, doi = {10.1038/d41586-018-04156-7}, pmid = {29643499}, issn = {1476-4687}, } @article {pmid29643498, year = {2018}, author = {Castelvecchi, D}, title = {How gravitational waves could solve some of the Universe's deepest mysteries.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {164-168}, doi = {10.1038/d41586-018-04157-6}, pmid = {29643498}, issn = {1476-4687}, } @article {pmid29643497, year = {2018}, author = {Khan, SA}, title = {Curtail climate-change effects using Singapore Index of Cities' Biodiversity.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {174}, doi = {10.1038/d41586-018-04168-3}, pmid = {29643497}, issn = {1476-4687}, mesh = {*Biodiversity ; Cities ; Climate ; *Climate Change ; Conservation of Natural Resources ; Ecosystem ; Singapore ; }, } @article {pmid29643495, year = {2018}, author = {Lazarev, VS and Nazarovets, SA}, title = {Don't dismiss citations to journals not published in English.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {174}, doi = {10.1038/d41586-018-04169-2}, pmid = {29643495}, issn = {1476-4687}, mesh = {*Bibliometrics ; *Journal Impact Factor ; Periodicals as Topic ; Publications ; Publishing ; }, } @article {pmid29643494, year = {2018}, author = {Svendsen, JC and Alstrup, AKO and Jensen, LF}, title = {Save a North Sea fish from becoming museum piece.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {174}, doi = {10.1038/d41586-018-04170-9}, pmid = {29643494}, issn = {1476-4687}, mesh = {Animals ; Conservation of Natural Resources/*trends ; Museums ; North Sea ; *Salmonidae ; }, } @article {pmid29643493, year = {2018}, author = {Hejnowicz, AP and Hartley, SE and Gilbert, N}, title = {Build two-way rapport for better policymaking.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {174}, doi = {10.1038/d41586-018-04167-4}, pmid = {29643493}, issn = {1476-4687}, mesh = {*Health Policy ; Interpersonal Relations ; *Policy Making ; }, } @article {pmid29643492, year = {2018}, author = {Finger, R}, title = {Take a holistic view when making pesticide policies stricter.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {174}, doi = {10.1038/d41586-018-04166-5}, pmid = {29643492}, issn = {1476-4687}, mesh = {Agriculture ; *Pesticides ; *Policy ; }, } @article {pmid29643490, year = {2018}, author = {}, title = {Ocean circulation is changing, and we need to know why.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {149}, doi = {10.1038/d41586-018-04322-x}, pmid = {29643490}, issn = {1476-4687}, } @article {pmid29643489, year = {2018}, author = {}, title = {How gravitational waves might help fundamental cosmology.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {149-150}, doi = {10.1038/d41586-018-04321-y}, pmid = {29643489}, issn = {1476-4687}, mesh = {*Astronomy ; Electromagnetic Phenomena ; *Gravitation ; }, } @article {pmid29643487, year = {2018}, author = {Landhuis, E}, title = {Outsourcing is in.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {263-265}, doi = {10.1038/d41586-018-04163-8}, pmid = {29643487}, issn = {1476-4687}, mesh = {Animals ; Clinical Trials as Topic/methods ; Data Interpretation, Statistical ; Datasets as Topic ; Drug Industry/economics/*methods ; Humans ; Outsourced Services/economics/organization & administration/*statistics & numerical data/*trends ; Quality Control ; Workforce ; }, } @article {pmid29643486, year = {2018}, author = {Bierhorst, P and Knill, E and Glancy, S and Zhang, Y and Mink, A and Jordan, S and Rommal, A and Liu, YK and Christensen, B and Nam, SW and Stevens, MJ and Shalm, LK}, title = {Experimentally generated randomness certified by the impossibility of superluminal signals.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {223-226}, doi = {10.1038/s41586-018-0019-0}, pmid = {29643486}, issn = {1476-4687}, abstract = {From dice to modern electronic circuits, there have been many attempts to build better devices to generate random numbers. Randomness is fundamental to security and cryptographic systems and to safeguarding privacy. A key challenge with random-number generators is that it is hard to ensure that their outputs are unpredictable1-3. For a random-number generator based on a physical process, such as a noisy classical system or an elementary quantum measurement, a detailed model that describes the underlying physics is necessary to assert unpredictability. Imperfections in the model compromise the integrity of the device. However, it is possible to exploit the phenomenon of quantum non-locality with a loophole-free Bell test to build a random-number generator that can produce output that is unpredictable to any adversary that is limited only by general physical principles, such as special relativity1-11. With recent technological developments, it is now possible to carry out such a loophole-free Bell test12-14,22. Here we present certified randomness obtained from a photonic Bell experiment and extract 1,024 random bits that are uniformly distributed to within 10-12. These random bits could not have been predicted according to any physical theory that prohibits faster-than-light (superluminal) signalling and that allows independent measurement choices. To certify and quantify the randomness, we describe a protocol that is optimized for devices that are characterized by a low per-trial violation of Bell inequalities. Future random-number generators based on loophole-free Bell tests may have a role in increasing the security and trust of our cryptographic systems and infrastructure.}, } @article {pmid29643485, year = {2018}, author = {Caesar, L and Rahmstorf, S and Robinson, A and Feulner, G and Saba, V}, title = {Observed fingerprint of a weakening Atlantic Ocean overturning circulation.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {191-196}, doi = {10.1038/s41586-018-0006-5}, pmid = {29643485}, issn = {1476-4687}, mesh = {Atlantic Ocean ; Atmosphere/chemistry ; Carbon Dioxide/analysis ; Global Warming/*statistics & numerical data ; Gulf of Mexico ; History, 20th Century ; History, 21st Century ; Hot Temperature ; Models, Theoretical ; Regression Analysis ; Seawater/*analysis ; *Water Movements ; }, abstract = {The Atlantic meridional overturning circulation (AMOC)-a system of ocean currents in the North Atlantic-has a major impact on climate, yet its evolution during the industrial era is poorly known owing to a lack of direct current measurements. Here we provide evidence for a weakening of the AMOC by about 3 ± 1 sverdrups (around 15 per cent) since the mid-twentieth century. This weakening is revealed by a characteristic spatial and seasonal sea-surface temperature 'fingerprint'-consisting of a pattern of cooling in the subpolar Atlantic Ocean and warming in the Gulf Stream region-and is calibrated through an ensemble of model simulations from the CMIP5 project. We find this fingerprint both in a high-resolution climate model in response to increasing atmospheric carbon dioxide concentrations, and in the temperature trends observed since the late nineteenth century. The pattern can be explained by a slowdown in the AMOC and reduced northward heat transport, as well as an associated northward shift of the Gulf Stream. Comparisons with recent direct measurements from the RAPID project and several other studies provide a consistent depiction of record-low AMOC values in recent years.}, } @article {pmid29643484, year = {2018}, author = {Thornalley, DJR and Oppo, DW and Ortega, P and Robson, JI and Brierley, CM and Davis, R and Hall, IR and Moffa-Sanchez, P and Rose, NL and Spooner, PT and Yashayaev, I and Keigwin, LD}, title = {Anomalously weak Labrador Sea convection and Atlantic overturning during the past 150 years.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {227-230}, doi = {10.1038/s41586-018-0007-4}, pmid = {29643484}, issn = {1476-4687}, mesh = {Arctic Regions ; Atlantic Ocean ; Climate Change/statistics & numerical data ; *Convection ; Fresh Water/analysis ; Greenland ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Medieval ; Ice Cover/chemistry ; Newfoundland and Labrador ; *Oceans and Seas ; Reproducibility of Results ; Seawater/*analysis ; Time Factors ; *Water Movements ; }, abstract = {The Atlantic meridional overturning circulation (AMOC) is a system of ocean currents that has an essential role in Earth's climate, redistributing heat and influencing the carbon cycle1, 2. The AMOC has been shown to be weakening in recent years 1 ; this decline may reflect decadal-scale variability in convection in the Labrador Sea, but short observational datasets preclude a longer-term perspective on the modern state and variability of Labrador Sea convection and the AMOC1, 3-5. Here we provide several lines of palaeo-oceanographic evidence that Labrador Sea deep convection and the AMOC have been anomalously weak over the past 150 years or so (since the end of the Little Ice Age, LIA, approximately AD 1850) compared with the preceding 1,500 years. Our palaeoclimate reconstructions indicate that the transition occurred either as a predominantly abrupt shift towards the end of the LIA, or as a more gradual, continued decline over the past 150 years; this ambiguity probably arises from non-AMOC influences on the various proxies or from the different sensitivities of these proxies to individual components of the AMOC. We suggest that enhanced freshwater fluxes from the Arctic and Nordic seas towards the end of the LIA-sourced from melting glaciers and thickened sea ice that developed earlier in the LIA-weakened Labrador Sea convection and the AMOC. The lack of a subsequent recovery may have resulted from hysteresis or from twentieth-century melting of the Greenland Ice Sheet 6 . Our results suggest that recent decadal variability in Labrador Sea convection and the AMOC has occurred during an atypical, weak background state. Future work should aim to constrain the roles of internal climate variability and early anthropogenic forcing in the AMOC weakening described here.}, } @article {pmid29643483, year = {2018}, author = {Palfreyman, J and Dickey, JM and Hotan, A and Ellingsen, S and van Straten, W}, title = {Alteration of the magnetosphere of the Vela pulsar during a glitch.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {219-222}, doi = {10.1038/s41586-018-0001-x}, pmid = {29643483}, issn = {1476-4687}, abstract = {As pulsars lose energy, primarily in the form of magnetic dipole radiation, their rotation slows down accordingly. For some pulsars, this spin-down is interrupted by occasional abrupt spin-up events known as glitches 1 . A glitch is hypothesized to be a catastrophic release of pinned vorticity 2 that provides an exchange of angular momentum between the superfluid outer core and the crust. This is manifested by a minute alteration in the rotation rate of the neutron star and its co-rotating magnetosphere, which is revealed by an abrupt change in the timing of observed radio pulses. Measurement of the flux density, polarization and single-pulse arrival times of the glitch with high time resolution may reveal the equation of state of the crustal superfluid, its drag-to-lift ratio and the parameters that describe its friction with the crust 3 . This has not hitherto been possible because glitch events happen unpredictably. Here we report single-pulse radio observations of a glitch in the Vela pulsar, which has a rotation frequency of 11.2 hertz. The glitch was detected on 2016 December 12 at 11:36 universal time, during continuous observations of the pulsar over a period of three years. We detected sudden changes in the pulse shape coincident with the glitch event: one pulse was unusually broad, the next pulse was missing (a 'null') and the following two pulses had unexpectedly low linear polarization. This sequence was followed by a 2.6-second interval during which pulses arrived later than usual, indicating that the glitch affects the magnetosphere.}, } @article {pmid29643482, year = {2018}, author = {Lee, J and Kitchaev, DA and Kwon, DH and Lee, CW and Papp, JK and Liu, YS and Lun, Z and Clément, RJ and Shi, T and McCloskey, BD and Guo, J and Balasubramanian, M and Ceder, G}, title = {Reversible Mn2+/Mn4+ double redox in lithium-excess cathode materials.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {185-190}, doi = {10.1038/s41586-018-0015-4}, pmid = {29643482}, issn = {1476-4687}, abstract = {There is an urgent need for low-cost, resource-friendly, high-energy-density cathode materials for lithium-ion batteries to satisfy the rapidly increasing need for electrical energy storage. To replace the nickel and cobalt, which are limited resources and are associated with safety problems, in current lithium-ion batteries, high-capacity cathodes based on manganese would be particularly desirable owing to the low cost and high abundance of the metal, and the intrinsic stability of the Mn4+ oxidation state. Here we present a strategy of combining high-valent cations and the partial substitution of fluorine for oxygen in a disordered-rocksalt structure to incorporate the reversible Mn2+/Mn4+ double redox couple into lithium-excess cathode materials. The lithium-rich cathodes thus produced have high capacity and energy density. The use of the Mn2+/Mn4+ redox reduces oxygen redox activity, thereby stabilizing the materials, and opens up new opportunities for the design of high-performance manganese-rich cathodes for advanced lithium-ion batteries.}, } @article {pmid29643443, year = {2018}, author = {Horvath, S and Raj, K}, title = {DNA methylation-based biomarkers and the epigenetic clock theory of ageing.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {371-384}, doi = {10.1038/s41576-018-0004-3}, pmid = {29643443}, issn = {1471-0064}, abstract = {Identifying and validating molecular targets of interventions that extend the human health span and lifespan has been difficult, as most clinical biomarkers are not sufficiently representative of the fundamental mechanisms of ageing to serve as their indicators. In a recent breakthrough, biomarkers of ageing based on DNA methylation data have enabled accurate age estimates for any tissue across the entire life course. These 'epigenetic clocks' link developmental and maintenance processes to biological ageing, giving rise to a unified theory of life course. Epigenetic biomarkers may help to address long-standing questions in many fields, including the central question: why do we age?}, } @article {pmid29643075, year = {2018}, author = {Carrow, JK and Cross, LM and Reese, RW and Jaiswal, MK and Gregory, CA and Kaunas, R and Singh, I and Gaharwar, AK}, title = {Widespread changes in transcriptome profile of human mesenchymal stem cells induced by two-dimensional nanosilicates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3905-E3913}, pmid = {29643075}, issn = {1091-6490}, support = {R03 EB023454/EB/NIBIB NIH HHS/United States ; }, mesh = {Clathrin/metabolism ; Endocytosis/drug effects ; *Gene Expression Profiling ; Gene Expression Regulation/*drug effects ; High-Throughput Nucleotide Sequencing ; Humans ; MAP Kinase Signaling System/*drug effects ; Mesenchymal Stem Cells/cytology/*metabolism ; *Nanoparticles ; Silicates/*pharmacology ; Transcriptome/*drug effects ; }, abstract = {Two-dimensional nanomaterials, an ultrathin class of materials such as graphene, nanoclays, transition metal dichalcogenides (TMDs), and transition metal oxides (TMOs), have emerged as a new generation of materials due to their unique properties relative to macroscale counterparts. However, little is known about the transcriptome dynamics following exposure to these nanomaterials. Here, we investigate the interactions of 2D nanosilicates, a layered clay, with human mesenchymal stem cells (hMSCs) at the whole-transcriptome level by high-throughput sequencing (RNA-seq). Analysis of cell-nanosilicate interactions by monitoring changes in transcriptome profile uncovered key biophysical and biochemical cellular pathways triggered by nanosilicates. A widespread alteration of genes was observed due to nanosilicate exposure as more than 4,000 genes were differentially expressed. The change in mRNA expression levels revealed clathrin-mediated endocytosis of nanosilicates. Nanosilicate attachment to the cell membrane and subsequent cellular internalization activated stress-responsive pathways such as mitogen-activated protein kinase (MAPK), which subsequently directed hMSC differentiation toward osteogenic and chondrogenic lineages. This study provides transcriptomic insight on the role of surface-mediated cellular signaling triggered by nanomaterials and enables development of nanomaterials-based therapeutics for regenerative medicine. This approach in understanding nanomaterial-cell interactions illustrates how change in transcriptomic profile can predict downstream effects following nanomaterial treatment.}, } @article {pmid29643074, year = {2018}, author = {Gehrmann, T and Pelkmans, JF and Ohm, RA and Vos, AM and Sonnenberg, ASM and Baars, JJP and Wösten, HAB and Reinders, MJT and Abeel, T}, title = {Nucleus-specific expression in the multinuclear mushroom-forming fungus Agaricus bisporus reveals different nuclear regulatory programs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4429-4434}, pmid = {29643074}, issn = {1091-6490}, mesh = {Agaricus/genetics/*metabolism ; Cell Nucleus/genetics/*metabolism ; Gene Expression Regulation, Fungal/*physiology ; RNA, Fungal/*biosynthesis/genetics ; RNA, Messenger/*biosynthesis/genetics ; Transcriptome/physiology ; Up-Regulation/*physiology ; }, abstract = {Many fungi are polykaryotic, containing multiple nuclei per cell. In the case of heterokaryons, there are different nuclear types within a single cell. It is unknown what the different nuclear types contribute in terms of mRNA expression levels in fungal heterokaryons. Each cell of the mushroom Agaricus bisporus contains two to 25 nuclei of two nuclear types originating from two parental strains. Using RNA-sequencing data, we assess the differential mRNA contribution of individual nuclear types and its functional impact. We studied differential expression between genes of the two nuclear types, P1 and P2, throughout mushroom development in various tissue types. P1 and P2 produced specific mRNA profiles that changed through mushroom development. Differential regulation occurred at the gene level, rather than at the locus, chromosomal, or nuclear level. P1 dominated mRNA production throughout development, and P2 showed more differentially up-regulated genes in important functional groups. In the vegetative mycelium, P2 up-regulated almost threefold more metabolism genes and carbohydrate active enzymes (cazymes) than P1, suggesting phenotypic differences in growth. We identified widespread transcriptomic variation between the nuclear types of A. bisporus Our method enables studying nucleus-specific expression, which likely influences the phenotype of a fungus in a polykaryotic stage. Our findings have a wider impact to better understand gene regulation in fungi in a heterokaryotic state. This work provides insight into the transcriptomic variation introduced by genomic nuclear separation.}, } @article {pmid29643073, year = {2018}, author = {Vaseva, II and Qudeimat, E and Potuschak, T and Du, Y and Genschik, P and Vandenbussche, F and Van Der Straeten, D}, title = {The plant hormone ethylene restricts Arabidopsis growth via the epidermis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4130-E4139}, pmid = {29643073}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Ethylenes/*metabolism ; Genetic Complementation Test ; Mutation ; Plant Epidermis/genetics/*metabolism ; Plant Growth Regulators/genetics/*metabolism ; }, abstract = {The gaseous hormone ethylene plays a key role in plant growth and development, and it is a major regulator of stress responses. It inhibits vegetative growth by restricting cell elongation, mainly through cross-talk with auxins. However, it remains unknown whether ethylene controls growth throughout all plant tissues or whether its signaling is confined to specific cell types. We employed a targeted expression approach to map the tissue site(s) of ethylene growth regulation. The ubiquitin E3 ligase complex containing Skp1, Cullin1, and the F-box protein EBF1 or EBF2 (SCFEBF1/2) target the degradation of EIN3, the master transcription factor in ethylene signaling. We coupled EBF1 and EBF2 to a number of cell type-specific promoters. Using phenotypic assays for ethylene response and mutant complementation, we revealed that the epidermis is the main site of ethylene action controlling plant growth in both roots and shoots. Suppression of ethylene signaling in the epidermis of the constitutive ethylene signaling mutant ctr1-1 was sufficient to rescue the mutant phenotype, pointing to the epidermis as a key cell type required for ethylene-mediated growth inhibition.}, } @article {pmid29643072, year = {2018}, author = {Christie, MR and McNickle, GG and French, RA and Blouin, MS}, title = {Life history variation is maintained by fitness trade-offs and negative frequency-dependent selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4441-4446}, pmid = {29643072}, issn = {1091-6490}, mesh = {Animals ; Female ; Longevity/*physiology ; Male ; Oncorhynchus mykiss/*physiology ; Oregon ; Reproduction/*physiology ; Selection, Genetic/*physiology ; }, abstract = {The maintenance of diverse life history strategies within and among species remains a fundamental question in ecology and evolutionary biology. By using a near-complete 16-year pedigree of 12,579 winter-run steelhead (Oncorhynchus mykiss) from the Hood River, Oregon, we examined the continued maintenance of two life history traits: the number of lifetime spawning events (semelparous vs. iteroparous) and age at first spawning (2-5 years). We found that repeat-spawning fish had more than 2.5 times the lifetime reproductive success of single-spawning fish. However, first-time repeat-spawning fish had significantly lower reproductive success than single-spawning fish of the same age, suggesting that repeat-spawning fish forego early reproduction to devote additional energy to continued survival. For single-spawning fish, we also found evidence for a fitness trade-off for age at spawning: older, larger males had higher reproductive success than younger, smaller males. For females, in contrast, we found that 3-year-old fish had the highest mean lifetime reproductive success despite the observation that 4- and 5-year-old fish were both longer and heavier. This phenomenon was explained by negative frequency-dependent selection: as 4- and 5-year-old fish decreased in frequency on the spawning grounds, their lifetime reproductive success became greater than that of the 3-year-old fish. Using a combination of mathematical and individual-based models parameterized with our empirical estimates, we demonstrate that both fitness trade-offs and negative frequency-dependent selection observed in the empirical data can theoretically maintain the diverse life history strategies found in this population.}, } @article {pmid29642951, year = {2018}, author = {Masci, E and Faillace, G and Longoni, M}, title = {Use of oxidized regenerated cellulose to achieve hemostasis during laparoscopic cholecystectomy: a retrospective cohort analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {239}, pmid = {29642951}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Blood Loss, Surgical/*prevention & control ; Cellulose, Oxidized/*therapeutic use ; Cholecystectomy, Laparoscopic/*adverse effects/methods ; Cholelithiasis/*surgery ; Female ; Hemostasis/*physiology ; *Hemostatic Techniques ; Humans ; Male ; Middle Aged ; *Outcome Assessment (Health Care) ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: Laparoscopic cholecystectomy is the first-choice treatment for symptomatic cholelithiasis. Though generally safe, this procedure is not without complications, with bleeding the most frequent cause of conversion to open cholecystectomy. Oxidized regenerated cellulose (ORC) added to conventional hemostatic strategies, is widely used to control bleeding during surgery despite limited evidence supporting its use. This retrospective study analyzed patients undergoing laparoscopic cholecystectomy in an Italian center over a 16-month period, between October 2014 and February 2016, who experienced uncontrollable bleeding despite the use of conventional hemostatic strategies, requiring the addition of ORC gauze (Emosist®).

RESULTS: Of the 530 patients who underwent laparoscopic cholecystectomy, 24 (4.5%) had uncontrollable bleeding from the liver bed. Of these, 62.5% had acute cholecystitis and 33.3% chronic cholecystitis; 1 patient was diagnosed with gallbladder carcinoma, postoperatively. Most patients had comorbidities, 16.7% had liver cirrhosis, and 37.5% used oral anticoagulants. The application of ORC rapidly controlled bleeding in all patients. Patients were discharged after a mean duration of 2.2 days. ORC was easy to use and well tolerated. Bleeding complications remain a relevant issue in laparoscopic cholecystectomy. ORC was able to promptly stop bleeding not adequately controlled by conventional methods and appears, therefore, to be a useful hemostat.}, } @article {pmid29642947, year = {2018}, author = {Irie, T and Motomiya, M and Iwasaki, N}, title = {Absence of flexor carpi radialis identified during volar approach for fixation of distal radius fracture: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {240}, pmid = {29642947}, issn = {1756-0500}, mesh = {Female ; Fracture Fixation, Internal/*methods ; Humans ; Middle Aged ; Muscle, Skeletal/*abnormalities ; Radius Fractures/*surgery ; Wrist/*abnormalities ; }, abstract = {BACKGROUND: Volar locking plate fixation of distal radius fractures is commonly performed because of its good clinical outcomes. The flexor carpi radialis (FCR) approach is one of the most popular approaches to dissecting the volar side of the distal radius because of its simplicity and safety. We describe an extremely rare case of an absent FCR identified during a volar approach for fixation of a distal radius fracture.

CASE PRESENTATION: A 59-year-old woman with distal radius fracture underwent surgery using the usual FCR approach and volar locking plate. We could not identify the absence of the FCR tendon preoperatively because of severe swelling of the distal forearm. At first, we wrongly identified the palmaris longus tendon as the FCR because it was the tendinous structure at the most radial location of the volar distal forearm. When we found the median nerve just radial to the palmaris longus tendon, we were then able to identify the anatomical abnormality in this case. To avoid iatrogenic neurovascular injuries, we changed the approach to the classic Henry's approach.

CONCLUSIONS: Although the FCR approach is commonly used for fixation of distal radius fractures because of its simplicity and safety, this is the first report of complete absence of the FCR during the commonly performed volar approach for fixation of a distal radius fracture, to our knowledge. Because the FCR is designated as a favorable landmark because of its superficially palpable location, strong and thick structure, and rare anatomical variations, there is the possibility of iatrogenic complications in cases of the absence of the FCR. We suggest that surgeons should have a detailed knowledge of the range of possible anomalies to complete the fixation of a distal radius fracture safely.}, } @article {pmid29642945, year = {2018}, author = {Sornapudi, TR and Nayak, R and Guthikonda, PK and Kethavath, S and Yellaboina, S and Kurukuti, S}, title = {RNA sequencing of murine mammary epithelial stem-like cells (HC11) undergoing lactogenic differentiation and its comparison with embryonic stem cells.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {241}, pmid = {29642945}, issn = {1756-0500}, support = {NIAB/CP/107/2012//National Institute of Animal Biotechnology/ ; 90/09/2012/SCRT(TF)/BMS//Indian Council of Medical Research/ ; }, mesh = {Animals ; Cell Differentiation/drug effects/*physiology ; Cells, Cultured ; Embryonic Stem Cells/drug effects/*metabolism ; Epithelial Cells/drug effects/*metabolism ; Female ; Glucocorticoids/*pharmacology ; Lactation/drug effects/*metabolism ; Mammary Glands, Animal/*cytology ; Mice ; Prolactin/*pharmacology ; *Sequence Analysis, RNA ; Signal Transduction/drug effects/*physiology ; Transcriptome ; }, abstract = {OBJECTIVES: Understanding of transcriptional networks specifying HC11 murine mammary epithelial stem cell-like cells (MEC) in comparison with embryonic stem cells (ESCs) and their rewiring, under the influence of glucocorticoids (GC) and prolactin (PRL) hormones, is critical for elucidating the mechanism of lactogenesis. In this data note, we provide RNA sequencing data from murine MECs and ESCs, MECs treated with steroid hormone alone and in combination with PRL. This data could help in understanding temporal dynamics of mRNA transcription that impact the process of lactogenesis associated with mammary gland development. Further integration of these data sets with existing datasets of cells derived from various stages of mammary gland development and different types of breast tumors, should pave the way for effective prognosis and to develop therapies for breast cancer.

DATA DESCRIPTION: We have generated RNA-sequencing data representing steady-state levels of mRNAs from murine ESCs, normal MECs (N), MECs primed (P) with hydrocortisone (HC) alone and in combination with PRL hormone by using Illumina sequencing platform. We have generated ~ 58 million reads for ESCs with an average length of ~ 100 nt and an average 115 million good quality mapped reads with an average length of ~ 150 nt for different stages of MECs differentiation.}, } @article {pmid29642940, year = {2018}, author = {Dai, Z and Coker, OO and Nakatsu, G and Wu, WKK and Zhao, L and Chen, Z and Chan, FKL and Kristiansen, K and Sung, JJY and Wong, SH and Yu, J}, title = {Multi-cohort analysis of colorectal cancer metagenome identified altered bacteria across populations and universal bacterial markers.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {70}, pmid = {29642940}, issn = {2049-2618}, support = {766613, 14106145, 14111216//RGC-GRF/International ; 2016YFC1303200//135 Program Project China/International ; 2013CB531401//973 Program China/International ; 2014BAI09B05//National Key Technology R&D Program/International ; }, mesh = {Aged ; Bacteria/*classification/*genetics ; Cell Transformation, Neoplastic ; Colorectal Neoplasms/diagnosis/*etiology ; Computational Biology/methods ; Female ; *Gastrointestinal Microbiome ; Gene Ontology ; Humans ; Male ; *Metagenome ; *Metagenomics/methods ; Middle Aged ; }, abstract = {BACKGROUND: Alterations of gut microbiota are associated with colorectal cancer (CRC) in different populations and several bacterial species were found to contribute to the tumorigenesis. The potential use of gut microbes as markers for early diagnosis has also been reported. However, cohort specific noises may distort the structure of microbial dysbiosis in CRC and lead to inconsistent results among studies. In this regard, our study targeted at exploring changes in gut microbiota that are universal across populations at species level.

RESULTS: Based on the combined analysis of 526 metagenomic samples from Chinese, Austrian, American, and German and French cohorts, seven CRC-enriched bacteria (Bacteroides fragilis, Fusobacterium nucleatum, Porphyromonas asaccharolytica, Parvimonas micra, Prevotella intermedia, Alistipes finegoldii, and Thermanaerovibrio acidaminovorans) have been identified across populations. The seven enriched bacterial markers classified cases from controls with an area under the receiver-operating characteristics curve (AUC) of 0.80 across the different populations. Abundance correlation analysis demonstrated that CRC-enriched and CRC-depleted bacteria respectively formed their own mutualistic networks, in which the latter was disjointed in CRC. The CRC-enriched bacteria have been found to be correlated with lipopolysaccharide and energy biosynthetic pathways.

CONCLUSIONS: Our study identified potential diagnostic bacterial markers that are robust across populations, indicating their potential universal use for non-invasive CRC diagnosis. We also elucidated the ecological networks and functional capacities of CRC-associated microbiota.}, } @article {pmid29642908, year = {2018}, author = {Ordinelli, A and Bernabò, N and Orsini, M and Mattioli, M and Barboni, B}, title = {Putative human sperm Interactome: a networks study.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {52}, pmid = {29642908}, issn = {1752-0509}, abstract = {BACKGROUND: For over sixty years, it has been known that mammalian spermatozoa immediately after ejaculation are virtually infertile. They became able to fertilize only after they reside for long time (hours to days) within female genital tract where they complete their functional maturation, the capacitation. This process is finely regulated by the interaction with the female environment and involves, in spermatozoa, a myriad of molecules as messengers and target of signals. Since, to date, a model able to represent the molecular interaction that characterize sperm physiology does not exist, we realized the Human Sperm Interactme Network3.0 (HSIN3.0) and its main component (HSNI3.0_MC), starting from the pathway active in male germ cells.

RESULTS: HSIN3.0 and HSIN3.0_MC are scale free networks, adherent to the Barabasi-Albert model, and are characterised by an ultra-small world topology. We found that they are resistant to random attacks and that are designed to respond quickly and specifically to external inputs. In addition, it has been possible to identify the most connected nodes (the hubs) and the bottlenecks nodes. This result allowed us to explore the control mechanisms active in driving sperm biochemical machinery and to verify the different levels of controls: party vs. date hubs and hubs vs. bottlenecks, thanks the availability of data from KO mice. Finally, we found that several key nodes represent molecules specifically involved in function that are thought to be not present or not active in sperm cells, such as control of cell cycle, proteins synthesis, nuclear trafficking, and immune response, thus potentially open new perspectives on the study of sperm biology.

CONCLUSIONS: For the first time we present a network representing putative human sperm interactome. This result gives very intriguing biological information and could contribute to the knowledge of spermatozoa, either in physiological or pathological conditions.}, } @article {pmid29642893, year = {2018}, author = {Sun, Y and Dinneny, JR}, title = {Q&A: How do gene regulatory networks control environmental responses in plants?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {38}, pmid = {29642893}, issn = {1741-7007}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {A gene regulatory network (GRN) describes the hierarchical relationship between transcription factors, associated proteins, and their target genes. Studying GRNs allows us to understand how a plant's genotype and environment are integrated to regulate downstream physiological responses. Current efforts in plants have focused on defining the GRNs that regulate functions such as development and stress response and have been performed primarily in genetically tractable model plant species such as Arabidopsis thaliana. Future studies will likely focus on how GRNs function in non-model plants and change over evolutionary time to allow for adaptation to extreme environments. This broader understanding will inform efforts to engineer GRNs to create tailored crop traits.}, } @article {pmid29642886, year = {2018}, author = {Schneijderberg, M and Schmitz, L and Cheng, X and Polman, S and Franken, C and Geurts, R and Bisseling, T}, title = {A genetically and functionally diverse group of non-diazotrophic Bradyrhizobium spp. colonizes the root endophytic compartment of Arabidopsis thaliana.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {61}, pmid = {29642886}, issn = {1471-2229}, support = {3100000843//European Research Council/International ; }, mesh = {Arabidopsis/*metabolism/*microbiology ; Bradyrhizobium/*physiology ; Nitrogen Fixation/physiology ; Plant Root Nodulation/physiology ; Root Nodules, Plant/*metabolism/*microbiology ; Soil Microbiology ; Symbiosis/physiology ; }, abstract = {BACKGROUND: Diazotrophic Bradyrhizobium spp. are well known for their ability to trigger nodule formation on a variety of legume species. In nodules, Bradyrhizobium utilizes plant-derived carbohydrates in exchange for fixed nitrogen. The genes essential for the nodulation and nitrogen-fixation trait are clustered in a genomic region, which is known as the 'symbiotic island'. Recently, novel non-diazotrophic Bradyrhizobium spp. have been found to be highly abundant in soils, suggesting that these species can also have a 'free-living' life history. However, whether non-diazotrophic Bradyrhizobium spp. can live in association with plants remains elusive.

RESULTS: In this study, we show that Bradyrhizobium spp. are common root endophytes of non-legume plant species - including Arabidopsis thaliana (Arabidopsis) - grown in an ecological setting. From a single Arabidopsis root, four Bradyrhizobium sp. strains (designated MOS001 to MOS004) were isolated. Comparative genome analysis revealed that these strains were genetically and functionally highly diverse, but did not harbour the nodulation and the nitrogen fixation gene clusters. Comparative colonization experiments, with MOS strains and nitrogen-fixing symbiotic strains, revealed that all tested Bradyrhizobium spp. can colonize the root endophytic compartment of Arabidopsis.

CONCLUSION: This study provides evidence that both diazotrophic and non-diazotrophic Bradyrhizobium spp. colonize the root endophytic compartment of a wide variety of plant species, including the model species Arabidopsis. This demonstrates that plant roots form a major ecological niche for Bradyrhizobium spp., which might be ancestral to the evolution of the nodulation and nitrogen-fixation trait in this genus.}, } @article {pmid29642872, year = {2018}, author = {Rodrigues, PS and Souza, MM and Melo, CAF and Pereira, TNS and Corrêa, RX}, title = {Karyotype diversity and 2C DNA content in species of the Caesalpinia group.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {25}, pmid = {29642872}, issn = {1471-2156}, support = {(Financial Support)//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; (Financial Support)//Fundação de Amparo à Pesquisa do Estado da Bahia/ ; (Financial Support and Grant)//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/ ; (Financial Support)//Universidade Estadual de Santa Cruz/ ; }, abstract = {BACKGROUND: The Leguminosae family is the third-largest family of angiosperms, and Caesalpinioideae is its second-largest subfamily. A great number of species (approximately 205) are found in the Caesalpinia group within this subfamily; together with these species' phenotypic plasticity and the similarities in their morphological descriptors, make this a complex group for taxonomic and phylogenetic studies. The objective of the present work was to evaluate the karyotypic diversity and the 2C DNA content variation in 10 species of the Caesalpinia group, representing six genera: Paubrasilia, Caesalpinia, Cenostigma, Poincianella, Erythrostemon and Libidibia. The GC-rich heterochromatin and 45S rDNA sites (which are used as chromosome markers) were located to evaluate the karyotype diversity in the clade. The variation in the 2C DNA content was determined through flow cytometry.

RESULTS: The fluorochrome banding indicated that the chromomycin A3+/4',6-diamidino-2-phenylindole- blocks were exclusively in the terminal regions of the chromosomes, coinciding with 45S rDNA sites in all analyzed species. Physical mapping of the species (through fluorescence in situ hybridization) revealed variation in the size of the hybridization signals and in the number and distribution of the 45S rDNA sites. All hybridization sites were in the terminal regions of the chromosomes. In addition, all species had a hybridization site in the fourth chromosome pair. The 2C DNA content ranged from 1.54 pg in Erythrostemon calycina to 2.82 pg in the Paubrasilia echinata large-leaf variant. The Pa. echinata small-leaf variant was isolated from the other leaf variants through Scoot-Knott clustering.

CONCLUSIONS: The chromosome diversity and the variation in the 2C DNA content reinforce that the actual taxonomy and clustering of the analyzed taxa requires more genera that were previously proposed. This fact indicates that taxonomy, phylogeny and cytoevolutionary inference related to the complex Caesalpinia group have to be done through integrative evaluation.}, } @article {pmid29642870, year = {2018}, author = {Hohmann, N and Koch, MA}, title = {Correction to: An Arabidopsis introgression zone studied at high spatio-temporal resolution: interglacial and multiple genetic contact exemplified using whole nuclear and plastid genomes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {245}, pmid = {29642870}, issn = {1471-2164}, abstract = {ᅟ: Upon publication of the original article [1], the authors had flagged that there was an error in Fig. 1c, as the key in this figure was displaying incorrectly. The colours had not displayed in the key in the final published article, and instead appear as plain white.}, } @article {pmid29642859, year = {2018}, author = {Wachter, S and Raghavan, R and Wachter, J and Minnick, MF}, title = {Identification of novel MITEs (miniature inverted-repeat transposable elements) in Coxiella burnetii: implications for protein and small RNA evolution.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {247}, pmid = {29642859}, issn = {1471-2164}, support = {R03 AI133023/AI/NIAID NIH HHS/United States ; 51040-MUSR12015-03//Montana University System Research Initiative/ ; }, mesh = {Bacterial Proteins/genetics ; Base Sequence ; Conserved Sequence ; Coxiella burnetii/*genetics ; *DNA Transposable Elements ; Evolution, Molecular ; Genetic Linkage ; Genetic Loci ; Genome, Bacterial ; *Inverted Repeat Sequences ; Nucleic Acid Conformation ; Peptides/genetics ; RNA, Small Untranslated/chemistry/*genetics ; Sequence Alignment ; }, abstract = {BACKGROUND: Coxiella burnetii is a Gram-negative gammaproteobacterium and zoonotic agent of Q fever. C. burnetii's genome contains an abundance of pseudogenes and numerous selfish genetic elements. MITEs (miniature inverted-repeat transposable elements) are non-autonomous transposons that occur in all domains of life and are thought to be insertion sequences (ISs) that have lost their transposase function. Like most transposable elements (TEs), MITEs are thought to play an active role in evolution by altering gene function and expression through insertion and deletion activities. However, information regarding bacterial MITEs is limited.

RESULTS: We describe two MITE families discovered during research on small non-coding RNAs (sRNAs) of C. burnetii. Two sRNAs, Cbsr3 and Cbsr13, were found to originate from a novel MITE family, termed QMITE1. Another sRNA, CbsR16, was found to originate from a separate and novel MITE family, termed QMITE2. Members of each family occur ~ 50 times within the strains evaluated. QMITE1 is a typical MITE of 300-400 bp with short (2-3 nt) direct repeats (DRs) of variable sequence and is often found overlapping annotated open reading frames (ORFs). Additionally, QMITE1 elements possess sigma-70 promoters and are transcriptionally active at several loci, potentially influencing expression of nearby genes. QMITE2 is smaller (150-190 bps), but has longer (7-11 nt) DRs of variable sequences and is mainly found in the 3' untranslated region of annotated ORFs and intergenic regions. QMITE2 contains a GTAG repetitive extragenic palindrome (REP) that serves as a target for IS1111 TE insertion. Both QMITE1 and QMITE2 display inter-strain linkage and sequence conservation, suggesting that they are adaptive and existed before divergence of C. burnetii strains.

CONCLUSIONS: We have discovered two novel MITE families of C. burnetii. Our finding that MITEs serve as a source for sRNAs is novel. QMITE2 has a unique structure and occurs in large or small versions with unique DRs that display linkage and sequence conservation between strains, allowing for tracking of genomic rearrangements. QMITE1 and QMITE2 copies are hypothesized to influence expression of neighboring genes involved in DNA repair and virulence through transcriptional interference and ribonuclease processing.}, } @article {pmid29642857, year = {2018}, author = {Wong, DCJ and Zhang, L and Merlin, I and Castellarin, SD and Gambetta, GA}, title = {Structure and transcriptional regulation of the major intrinsic protein gene family in grapevine.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {248}, pmid = {29642857}, issn = {1471-2164}, support = {Initiative of Excellence (IdEx) program, doctoral school of life and health sciences//Université de Bordeaux/ ; Cluster of Excellence COTE (ANR-10-LABX-45, within the Water Stress project)//Université de Bordeaux/ ; 10R18459//University of British Columbia/ ; 10R21188//Genome British Columbia/ ; 10R23082//Natural Sciences and Engineering Research Council of Canada/ ; }, mesh = {Aquaporins/classification/*genetics ; *Gene Expression Regulation, Plant ; *Gene Regulatory Networks ; *Multigene Family ; Phylogeny ; Plant Proteins/classification/*genetics ; Promoter Regions, Genetic ; Transcription, Genetic ; Vitis/*genetics ; }, abstract = {BACKGROUND: The major intrinsic protein (MIP) family is a family of proteins, including aquaporins, which facilitate water and small molecule transport across plasma membranes. In plants, MIPs function in a huge variety of processes including water transport, growth, stress response, and fruit development. In this study, we characterize the structure and transcriptional regulation of the MIP family in grapevine, describing the putative genome duplication events leading to the family structure and characterizing the family's tissue and developmental specific expression patterns across numerous preexisting microarray and RNAseq datasets. Gene co-expression network (GCN) analyses were carried out across these datasets and the promoters of each family member were analyzed for cis-regulatory element structure in order to provide insight into their transcriptional regulation.

RESULTS: A total of 29 Vitis vinifera MIP family members (excluding putative pseudogenes) were identified of which all but two were mapped onto Vitis vinifera chromosomes. In this study, segmental duplication events were identified for five plasma membrane intrinsic protein (PIP) and four tonoplast intrinsic protein (TIP) genes, contributing to the expansion of PIPs and TIPs in grapevine. Grapevine MIP family members have distinct tissue and developmental expression patterns and hierarchical clustering revealed two primary groups regardless of the datasets analyzed. Composite microarray and RNA-seq gene co-expression networks (GCNs) highlighted the relationships between MIP genes and functional categories involved in cell wall modification and transport, as well as with other MIPs revealing a strong co-regulation within the family itself. Some duplicated MIP family members have undergone sub-functionalization and exhibit distinct expression patterns and GCNs. Cis-regulatory element (CRE) analyses of the MIP promoters and their associated GCN members revealed enrichment for numerous CREs including AP2/ERFs and NACs.

CONCLUSIONS: Combining phylogenetic analyses, gene expression profiling, gene co-expression network analyses, and cis-regulatory element enrichment, this study provides a comprehensive overview of the structure and transcriptional regulation of the grapevine MIP family. The study highlights the duplication and sub-functionalization of the family, its strong coordinated expression with genes involved in growth and transport, and the putative classes of TFs responsible for its regulation.}, } @article {pmid29642854, year = {2018}, author = {Li, Z and Liu, X and Zhang, P and Han, R and Sun, G and Jiang, R and Wang, Y and Liu, X and Li, W and Kang, X and Tian, Y}, title = {Comparative transcriptome analysis of hypothalamus-regulated feed intake induced by exogenous visfatin in chicks.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {249}, pmid = {29642854}, issn = {1471-2164}, support = {31372330//National Natural Science Foundation of China/ ; IRT16R23//Program for Innovation Research Team of Ministry of Education/ ; U1704233//NSFC-Henan joint grant/ ; 172102110045//Key Science and Technology Research Project of Henan Province/ ; }, mesh = {Animals ; Chickens/blood/*genetics/metabolism ; Cluster Analysis ; Eating/drug effects ; Feeding Behavior/*drug effects ; Gene Expression Profiling ; Gene Ontology ; Hormones/blood ; Hypothalamus/drug effects/*metabolism ; Injections, Intraventricular ; Nicotinamide Phosphoribosyltransferase/administration & dosage/*pharmacology ; Protein Interaction Mapping ; RNA, Messenger/chemistry/metabolism ; Real-Time Polymerase Chain Reaction ; Sequence Analysis, RNA ; Signal Transduction ; *Transcriptome ; }, abstract = {BACKGROUND: The intracerebroventricular injection of visfatin increases feed intake. However, little is known about the molecular mechanism in chicks. This study was conducted to assess the effect of visfatin on the feeding behavior of chicks and the associated molecular mechanism.

RESULTS: In response to the intraventricular injection of 40 ng and 400 ng visfatin, feed intake in chicks was significantly increased, and the concentrations of glucose, insulin, TG, HDL and LDL were significantly altered. Using RNA-seq, we identified DEGs in the chick hypothalamus at 60 min after injection with various doses of visfatin. In total, 325, 85 and 519 DEGs were identified in the treated chick hypothalamus in the LT vs C, HT vs C and LT vs HT comparisons, respectively. The changes in the expression profiles of DEGs, GO functional categories, KEGG pathways, and PPI networks by visfatin-mediated regulation of feed intake were analyzed. The DEGs were grouped into 8 clusters based on their expression patterns via K-mean clustering; there were 14 appetite-related DEGs enriched in the hormone activity GO term. The neuroactive ligand-receptor interaction pathway was the key pathway affected by visfatin. The PPI analysis of DEGs showed that POMC was a hub gene that interacted with the maximum number of nodes and ingestion-related pathways, including POMC, CRH, AgRP, NPY, TRH, VIP, NPYL, CGA and TSHB.

CONCLUSION: These common DEGs were enriched in the hormone activity GO term and the neuroactive ligand-receptor interaction pathway. Therefore, visfatin causes hyperphagia via the POMC/CRH and NPY/AgRP signaling pathways. These results provide valuable information about the molecular mechanisms of the regulation of food intake by visfatin.}, } @article {pmid29642853, year = {2018}, author = {Zhang, Y and Qin, C and Yang, L and Lu, R and Zhao, X and Nie, G}, title = {A comparative genomics study of carbohydrate/glucose metabolic genes: from fish to mammals.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {246}, pmid = {29642853}, issn = {1471-2164}, support = {31401014//National Natural Science Foundation of China/ ; 31372545//National Natural Science Foundation of China/ ; 31672671//National Natural Science Foundation of China/ ; 14IRTSTHN013//Program for Innovative Research Team (in Science and Technology) in University of Henan Province/ ; 2015FB177//Natural Science Foundation of Yunnan Province/ ; qd15187//the PhD Start-up Fund of Henan Normal University/ ; }, mesh = {Animals ; Carbohydrate Metabolism/*genetics ; Chickens/genetics ; Data Mining ; Diabetes Mellitus, Type 2/genetics/metabolism ; Genomics ; Glucose/*metabolism ; Humans ; Mice ; Xenopus ; Zebrafish/genetics ; }, abstract = {BACKGROUND: Glucose plays a key role as an energy source in most mammals, but its importance in fish appears to be limited that so far seemed to belong to diabetic humans only. Several laboratories worldwide have made important efforts in order to better understand this strange phenotype observed in fish. However, the mechanism of carbohydrate/glucose metabolism is astonishingly complex. Why basal glycaemia is different between fish and mammals and how carbohydrate metabolism is different amongst organisms is largely uncharted territory. The utilization of comparative systems biology with model vertebrates to explore fish metabolism has become an essential approach to unravelling hidden in vivo mechanisms.

RESULTS: In this study, we first built a database containing 791, 593, 523, 666 and 698 carbohydrate/glucose metabolic genes from the genomes of Danio rerio, Xenopus tropicalis, Gallus gallus, Mus musculus and Homo sapiens, respectively, and most of these genes in our database are predicted to encode specific enzymes that play roles in defined reactions; over 57% of these genes are related to human type 2 diabetes. Then, we systematically compared these genes and found that more than 70% of the carbohydrate/glucose metabolic genes are conserved in the five species. Interestingly, there are 4 zebrafish-specific genes (si:ch211-167b20.8, CABZ01043017.1, socs9 and eif4e1c) and 1 human-specific gene (CALML6) that may alter glucose utilization in their corresponding species. Interestingly, these 5 genes are all carbohydrate regulation factors, but the enzymes themselves are involved in insulin regulation pathways. Lastly, in order to facilitate the use of our data sets, we constructed a glucose metabolism database platform (http://101.200.43.1:10000/).

CONCLUSIONS: This study provides the first systematic genomic insights into carbohydrate/glucose metabolism. After exhaustive analysis, we found that most metabolic genes are conserved in vertebrates. This work may resolve some of the complexities of carbohydrate/glucose metabolic heterogeneity amongst different vertebrates and may provide a reference for the treatment of diabetes and for applications in the aquaculture industry.}, } @article {pmid29642852, year = {2018}, author = {Deli, T and Kalkan, E and Karhan, SÜ and Uzunova, S and Keikhosravi, A and Bilgin, R and Schubart, CD}, title = {Parapatric genetic divergence among deep evolutionary lineages in the Mediterranean green crab, Carcinus aestuarii (Brachyura, Portunoidea, Carcinidae), accounts for a sharp phylogeographic break in the Eastern Mediterranean.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {53}, pmid = {29642852}, issn = {1471-2148}, support = {09S101//Research Fund of Boğaziçi University in Istanbul/International ; PPP program, D/08/02059//Deutscher Akademischer Austauschdienst/International ; }, mesh = {Animals ; Biological Evolution ; Brachyura/*classification/*genetics ; Cyclooxygenase 1/genetics ; DNA, Mitochondrial/genetics ; Genetic Drift ; Genetic Variation ; Mediterranean Sea ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Recently, population genetic studies of Mediterranean marine species highlighted patterns of genetic divergence and phylogeographic breaks, due to the interplay between impacts of Pleistocene climate shifts and contemporary hydrographical barriers. These factors markedly shaped the distribution of marine organisms and their genetic makeup. The present study is part of an ongoing effort to understand the phylogeography and evolutionary history of the highly dispersive Mediterranean green crab, Carcinus aestuarii (Nardo, 1847), across the Mediterranean Sea. Recently, marked divergence between two highly separated haplogroups (genetic types I and II) of C. aestuarii was discerned across the Siculo-Tunisian Strait, suggesting an Early Pleistocene vicariant event. In order to better identify phylogeographic patterns in this species, a total of 263 individuals from 22 Mediterranean locations were analysed by comparing a 587 basepair region of the mitochondrial gene Cox1 (cytochrome oxidase subunit 1). The examined dataset is composed of both newly generated sequences (76) and previously investigated ones (187).

RESULTS: Our results unveiled the occurrence of a highly divergent haplogroup (genetic type III) in the most north-eastern part of the Mediterranean Sea. Divergence between the most distinct type III and the common ancestor of both types I and II corresponds to the Early Pleistocene and coincides with the historical episode of separation between types I and II. Our results also revealed strong genetic divergence among adjacent regions (separating the Aegean and Marmara seas from the remaining distribution zone) and confirmed a sharp phylogeographic break across the Eastern Mediterranean. The recorded parapatric genetic divergence, with the potential existence of a contact zone between both groups in the Ionian Sea and notable differences in the demographic history, suggest the likely impact of paleoclimatic events, as well as past and contemporary oceanographic processes, in shaping genetic variability of this species.

CONCLUSIONS: Our findings not only provide further evidence for the complex evolutionary history of the green crab in the Mediterranean Sea, but also stress the importance of investigating peripheral areas in the species' distribution zone in order to fully understand the distribution of genetic diversity and unravel hidden genetic units and local patterns of endemism.}, } @article {pmid29642851, year = {2018}, author = {Lokits, AD and Indrischek, H and Meiler, J and Hamm, HE and Stadler, PF}, title = {Tracing the evolution of the heterotrimeric G protein α subunit in Metazoa.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {51}, pmid = {29642851}, issn = {1471-2148}, support = {EY006062/NH/NIH HHS/United States ; EY010291/NH/NIH HHS/United States ; GM080403/NH/NIH HHS/United States ; GM099842/NH/NIH HHS/United States ; 100148833/22117017//Volkswagen Foundation/International ; 100227413//Volkswagen Foundation/International ; }, mesh = {Animals ; DNA-Binding Proteins/genetics ; *Evolution, Molecular ; GTP-Binding Protein alpha Subunits/chemistry/*genetics/metabolism ; Gene Duplication ; Nucleotide Motifs ; Phylogeny ; Retroelements ; Signal Transduction ; Vertebrates/classification/*genetics ; }, abstract = {BACKGROUND: Heterotrimeric G proteins are fundamental signaling proteins composed of three subunits, Gα and a Gβγ dimer. The role of Gα as a molecular switch is critical for transmitting and amplifying intracellular signaling cascades initiated by an activated G protein Coupled Receptor (GPCR). Despite their biochemical and therapeutic importance, the study of G protein evolution has been limited to the scope of a few model organisms. Furthermore, of the five primary Gα subfamilies, the underlying gene structure of only two families has been thoroughly investigated outside of Mammalia evolution. Therefore our understanding of Gα emergence and evolution across phylogeny remains incomplete.

RESULTS: We have computationally identified the presence and absence of every Gα gene (GNA-) across all major branches of Deuterostomia and evaluated the conservation of the underlying exon-intron structures across these phylogenetic groups. We provide evidence of mutually exclusive exon inclusion through alternative splicing in specific lineages. Variations of splice site conservation and isoforms were found for several paralogs which coincide with conserved, putative motifs of DNA-/RNA-binding proteins. In addition to our curated gene annotations, within Primates, we identified 15 retrotranspositions, many of which have undergone pseudogenization. Most importantly, we find numerous deviations from previous findings regarding the presence and absence of individual GNA- genes, nuanced differences in phyla-specific gene copy numbers, novel paralog duplications and subsequent intron gain and loss events.

CONCLUSIONS: Our curated annotations allow us to draw more accurate inferences regarding the emergence of all Gα family members across Metazoa and to present a new, updated theory of Gα evolution. Leveraging this, our results are critical for gaining new insights into the co-evolution of the Gα subunit and its many protein binding partners, especially therapeutically relevant G protein - GPCR signaling pathways which radiated in Vertebrata evolution.}, } @article {pmid29642848, year = {2018}, author = {Hameed, PN and Verspoor, K and Kusljic, S and Halgamuge, S}, title = {A two-tiered unsupervised clustering approach for drug repositioning through heterogeneous data integration.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {129}, pmid = {29642848}, issn = {1471-2105}, mesh = {Algorithms ; Cluster Analysis ; Computational Biology ; *Drug Repositioning ; Humans ; Pharmaceutical Preparations/classification ; *Statistics as Topic ; }, abstract = {BACKGROUND: Drug repositioning is the process of identifying new uses for existing drugs. Computational drug repositioning methods can reduce the time, costs and risks of drug development by automating the analysis of the relationships in pharmacology networks. Pharmacology networks are large and heterogeneous. Clustering drugs into small groups can simplify large pharmacology networks, these subgroups can also be used as a starting point for repositioning drugs. In this paper, we propose a two-tiered drug-centric unsupervised clustering approach for drug repositioning, integrating heterogeneous drug data profiles: drug-chemical, drug-disease, drug-gene, drug-protein and drug-side effect relationships.

RESULTS: The proposed drug repositioning approach is threefold; (i) clustering drugs based on their homogeneous profiles using the Growing Self Organizing Map (GSOM); (ii) clustering drugs based on drug-drug relation matrices based on the previous step, considering three state-of-the-art graph clustering methods; and (iii) inferring drug repositioning candidates and assigning a confidence value for each identified candidate. In this paper, we compare our two-tiered clustering approach against two existing heterogeneous data integration approaches with reference to the Anatomical Therapeutic Chemical (ATC) classification, using GSOM. Our approach yields Normalized Mutual Information (NMI) and Standardized Mutual Information (SMI) of 0.66 and 36.11, respectively, while the two existing methods yield NMI of 0.60 and 0.64 and SMI of 22.26 and 33.59. Moreover, the two existing approaches failed to produce useful cluster separations when using graph clustering algorithms while our approach is able to identify useful clusters for drug repositioning. Furthermore, we provide clinical evidence for four predicted results (Chlorthalidone, Indomethacin, Metformin and Thioridazine) to support that our proposed approach can be reliably used to infer ATC code and drug repositioning.

CONCLUSION: The proposed two-tiered unsupervised clustering approach is suitable for drug clustering and enables heterogeneous data integration. It also enables identifying reliable repositioning drug candidates with reference to ATC therapeutic classification. The repositioning drug candidates identified consistently by multiple clustering algorithms and with high confidence have a higher possibility of being effective repositioning candidates.}, } @article {pmid29642846, year = {2018}, author = {Sivade Dumousseau, M and Koch, M and Shrivastava, A and Alonso-López, D and De Las Rivas, J and Del-Toro, N and Combe, CW and Meldal, BHM and Heimbach, J and Rappsilber, J and Sullivan, J and Yehudi, Y and Orchard, S}, title = {JAMI: a Java library for molecular interactions and data interoperability.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {133}, pmid = {29642846}, issn = {1471-2105}, support = {BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 203149//Wellcome Trust/United Kingdom ; 103139//Wellcome Trust/United Kingdom ; 063412//Wellcome Trust/United Kingdom ; 103139//Wellcome Trust/United Kingdom ; 063412//Wellcome Trust/United Kingdom ; 203149//Wellcome Trust/United Kingdom ; }, mesh = {Databases, Protein ; Humans ; *Programming Languages ; Protein Interaction Maps ; Proteomics ; *Software ; *Statistics as Topic ; }, abstract = {BACKGROUND: A number of different molecular interactions data download formats now exist, designed to allow access to these valuable data by diverse user groups. These formats include the PSI-XML and MITAB standard interchange formats developed by Molecular Interaction workgroup of the HUPO-PSI in addition to other, use-specific downloads produced by other resources. The onus is currently on the user to ensure that a piece of software is capable of read/writing all necessary versions of each format. This problem may increase, as data providers strive to meet ever more sophisticated user demands and data types.

RESULTS: A collaboration between EMBL-EBI and the University of Cambridge has produced JAMI, a single library to unify standard molecular interaction data formats such as PSI-MI XML and PSI-MITAB. The JAMI free, open-source library enables the development of molecular interaction computational tools and pipelines without the need to produce different versions of software to read different versions of the data formats.

CONCLUSION: Software and tools developed on top of the JAMI framework are able to integrate and support both PSI-MI XML and PSI-MITAB. The use of JAMI avoids the requirement to chain conversions between formats in order to reach a desired output format and prevents code and unit test duplication as the code becomes more modular. JAMI's model interfaces are abstracted from the underlying format, hiding the complexity and requirements of each data format from developers using JAMI as a library.}, } @article {pmid29642844, year = {2018}, author = {Baek, SY and Kang, JH and Jo, SH and Jang, JE and Byeon, SY and Wang, JH and Lee, HG and Choi, JK and Lee, HJ}, title = {Contrasting life histories contribute to divergent patterns of genetic diversity and population connectivity in freshwater sculpin fishes.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {52}, pmid = {29642844}, issn = {1471-2148}, support = {NRF-2014R1A1A2059401//National Research Foundation of Korea/International ; NRF-2016R1D1A1B03934959//National Research Foundation of Korea/International ; Long-term changes in structure and function in the marine ecosystems of Korea//Ministry of Oceans and Fisheries/International ; Sangji University Research Fund, 2014//Sangji University/International ; }, mesh = {Animals ; Bayes Theorem ; Biological Evolution ; DNA, Mitochondrial/genetics ; *Genetic Variation ; Genetics, Population ; Larva/genetics ; Microsatellite Repeats ; Perciformes/*classification/*genetics ; Phylogeny ; Republic of Korea ; Rivers ; }, abstract = {BACKGROUND: Life history characteristics are considered important factors influencing the evolutionary processes of natural populations, including the patterns of population genetic structure of a species. The sister species Cottus hangiongensis and C. koreanus are small bottom-dwelling freshwater sculpin fishes from South Korea that display marked life history divergence but are morphologically nearly indistinguishable. Cottus hangiongensis evolved an 'amphidromous' life history with a post-hatching pelagic larval phase. They spawn many small eggs in the low reaches of rivers, and hatched larvae migrate to the sea before returning to grow to maturity in the river mouth. In contrast, C. koreanus evolved a 'fluvial' landlocked type with benthic larvae. They release a smaller number of larger eggs, and the larvae undergo direct development, remaining benthic in the upstream rivers throughout their entire lives. We tested whether there were differences in patterns and levels of within-population genetic diversities and spatial population structure between the two closely related Korean sculpins using mitochondrial DNA control region sequences and seven nuclear microsatellite loci.

RESULTS: The combined analyses of both marker sets revealed that C. hangiongensis harboured considerably higher levels of within-population genetic diversities (e.g. haplotype/allelic richness, heterozygosities) than C. koreanus. In contrast, the fluvial sculpin exhibited noticeably more spatial population structure than did the amphidromous sculpin, as suggested by pairwise FST statistics. The finding that C. hangiongensis individuals comprised a single random mating population across the east-flowing river basins in the Korean Peninsula, whereas C. koreanus individuals comprised genetically discrete individual populations, was further supported by an individual-based Bayesian population assignment and also factorial correspondence analyses.

CONCLUSIONS: The higher genetic diversity, but lower population structure, of the amphidromous sculpin relative to the fluvial sculpin may have resulted from its greater larval dispersal and also possibly, higher fecundity accompanied by an amphidromous life history. Hence, we conclude that contrasting early life histories - including the presence or absence of the pelagic larval phase - may have led to divergent patterns of within-population genetic diversities and spatial population structure between the sister Cottus species following speciation from a common ancestor of marine sculpin.}, } @article {pmid29642843, year = {2018}, author = {Oghabian, A and Greco, D and Frilander, MJ}, title = {IntEREst: intron-exon retention estimator.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {130}, pmid = {29642843}, issn = {1471-2105}, support = {140087//Academy of Finland/International ; 284601//Academy of Finland/International ; 275151//Academy of Finland/International ; 292307//Academy of Finland/International ; 308657//Academy of Finland/International ; }, mesh = {Base Pairing/genetics ; Computational Biology/*methods ; Down-Regulation/genetics ; Exons/*genetics ; Genome, Human ; Humans ; Introns/*genetics ; Myelodysplastic Syndromes/genetics ; Sample Size ; *Software ; Up-Regulation/genetics ; }, abstract = {BACKGROUND: In-depth study of the intron retention levels of transcripts provide insights on the mechanisms regulating pre-mRNA splicing efficiency. Additionally, detailed analysis of retained introns can link these introns to post-transcriptional regulation or identify aberrant splicing events in human diseases.

RESULTS: We present IntEREst, Intron-Exon Retention Estimator, an R package that supports rigorous analysis of non-annotated intron retention events (in addition to the ones annotated by RefSeq or similar databases), and support intra-sample in addition to inter-sample comparisons. It accepts binary sequence alignment/map (.bam) files as input and determines genome-wide estimates of intron retention or exon-exon junction levels. Moreover, it includes functions for comparing subsets of user-defined introns (e.g. U12-type vs U2-type) and its plotting functions allow visualization of the distribution of the retention levels of the introns. Statistical methods are adapted from the DESeq2, edgeR and DEXSeq R packages to extract the significantly more or less retained introns. Analyses can be performed either sequentially (on single core) or in parallel (on multiple cores). We used IntEREst to investigate the U12- and U2-type intron retention in human and plant RNAseq dataset with defects in the U12-dependent spliceosome due to mutations in the ZRSR2 component of this spliceosome. Additionally, we compared the retained introns discovered by IntEREst with that of other methods and studies.

CONCLUSION: IntEREst is an R package for Intron retention and exon-exon junction levels analysis of RNA-seq data. Both the human and plant analyses show that the U12-type introns are retained at higher level compared to the U2-type introns already in the control samples, but the retention is exacerbated in patient or plant samples carrying a mutated ZRSR2 gene. Intron retention events caused by ZRSR2 mutation that we discovered using IntEREst (DESeq2 based function) show considerable overlap with the retained introns discovered by other methods (e.g. IRFinder and edgeR based function of IntEREst). Our results indicate that increase in both the number of biological replicates and the depth of sequencing library promote the discovery of retained introns, but the effect of library size gradually decreases with more than 35 million reads mapped to the introns.}, } @article {pmid29642842, year = {2018}, author = {Mercier, J and Josso, A and Médigue, C and Vallenet, D}, title = {GROOLS: reactive graph reasoning for genome annotation through biological processes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {132}, pmid = {29642842}, issn = {1471-2105}, mesh = {Acinetobacter/genetics ; *Algorithms ; *Biological Phenomena ; Biosynthetic Pathways/genetics ; Computational Biology/*methods ; Cysteine/biosynthesis ; Databases, Factual ; *Genome ; *Molecular Sequence Annotation ; *Software ; }, abstract = {BACKGROUND: High quality functional annotation is essential for understanding the phenotypic consequences encoded in a genome. Despite improvements in bioinformatics methods, millions of sequences in databanks are not assigned reliable functions. The curation of protein functions in the context of biological processes is a way to evaluate and improve their annotation.

RESULTS: We developed an expert system using paraconsistent logic, named GROOLS (Genomic Rule Object-Oriented Logic System), that evaluates the completeness and the consistency of predicted functions through biological processes like metabolic pathways. Using a generic and hierarchical representation of knowledge, biological processes are modeled in a graph from which observations (i.e. predictions and expectations) are propagated by rules. At the end of the reasoning, conclusions are assigned to biological process components and highlight uncertainties and inconsistencies. Results on 14 microbial organisms are presented.

CONCLUSIONS: GROOLS software is designed to evaluate the overall accuracy of functional unit and pathway predictions according to organism experimental data like growth phenotypes. It assists biocurators in the functional annotation of proteins by focusing on missing or contradictory observations.}, } @article {pmid29642841, year = {2018}, author = {Sivade Dumousseau, M and Alonso-López, D and Ammari, M and Bradley, G and Campbell, NH and Ceol, A and Cesareni, G and Combe, C and De Las Rivas, J and Del-Toro, N and Heimbach, J and Hermjakob, H and Jurisica, I and Koch, M and Licata, L and Lovering, RC and Lynn, DJ and Meldal, BHM and Micklem, G and Panni, S and Porras, P and Ricard-Blum, S and Roechert, B and Salwinski, L and Shrivastava, A and Sullivan, J and Thierry-Mieg, N and Yehudi, Y and Van Roey, K and Orchard, S}, title = {Encompassing new use cases - level 3.0 of the HUPO-PSI format for molecular interactions.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {134}, pmid = {29642841}, issn = {1471-2105}, support = {R01 GM123126/GM/NIGMS NIH HHS/United States ; BB/L024179/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Databases, Protein ; Humans ; Mutation/genetics ; *Protein Interaction Maps ; Proteome/*metabolism ; *Proteomics ; Systems Biology ; }, abstract = {BACKGROUND: Systems biologists study interaction data to understand the behaviour of whole cell systems, and their environment, at a molecular level. In order to effectively achieve this goal, it is critical that researchers have high quality interaction datasets available to them, in a standard data format, and also a suite of tools with which to analyse such data and form experimentally testable hypotheses from them. The PSI-MI XML standard interchange format was initially published in 2004, and expanded in 2007 to enable the download and interchange of molecular interaction data. PSI-XML2.5 was designed to describe experimental data and to date has fulfilled this basic requirement. However, new use cases have arisen that the format cannot properly accommodate. These include data abstracted from more than one publication such as allosteric/cooperative interactions and protein complexes, dynamic interactions and the need to link kinetic and affinity data to specific mutational changes.

RESULTS: The Molecular Interaction workgroup of the HUPO-PSI has extended the existing, well-used XML interchange format for molecular interaction data to meet new use cases and enable the capture of new data types, following extensive community consultation. PSI-MI XML3.0 expands the capabilities of the format beyond simple experimental data, with a concomitant update of the tool suite which serves this format. The format has been implemented by key data producers such as the International Molecular Exchange (IMEx) Consortium of protein interaction databases and the Complex Portal.

CONCLUSIONS: PSI-MI XML3.0 has been developed by the data producers, data users, tool developers and database providers who constitute the PSI-MI workgroup. This group now actively supports PSI-MI XML2.5 as the main interchange format for experimental data, PSI-MI XML3.0 which additionally handles more complex data types, and the simpler, tab-delimited MITAB2.5, 2.6 and 2.7 for rapid parsing and download.}, } @article {pmid29642840, year = {2018}, author = {Girimurugan, SB and Liu, Y and Lung, PY and Vera, DL and Dennis, JH and Bass, HW and Zhang, J}, title = {iSeg: an efficient algorithm for segmentation of genomic and epigenomic data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {131}, pmid = {29642840}, issn = {1471-2105}, support = {R01 GM126558/GM/NIGMS NIH HHS/United States ; IOS Award 1444532//National Science Foundation/International ; R01GM126558/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Computer Simulation ; DNA Copy Number Variations/genetics ; *Databases, Genetic ; Deoxyribonucleases/metabolism ; *Epigenomics ; Genome ; Humans ; Models, Statistical ; Neoplasms/genetics ; Zea mays/genetics ; }, abstract = {BACKGROUND: Identification of functional elements of a genome often requires dividing a sequence of measurements along a genome into segments where adjacent segments have different properties, such as different mean values. Despite dozens of algorithms developed to address this problem in genomics research, methods with improved accuracy and speed are still needed to effectively tackle both existing and emerging genomic and epigenomic segmentation problems.

RESULTS: We designed an efficient algorithm, called iSeg, for segmentation of genomic and epigenomic profiles. iSeg first utilizes dynamic programming to identify candidate segments and test for significance. It then uses a novel data structure based on two coupled balanced binary trees to detect overlapping significant segments and update them simultaneously during searching and refinement stages. Refinement and merging of significant segments are performed at the end to generate the final set of segments. By using an objective function based on the p-values of the segments, the algorithm can serve as a general computational framework to be combined with different assumptions on the distributions of the data. As a general segmentation method, it can segment different types of genomic and epigenomic data, such as DNA copy number variation, nucleosome occupancy, nuclease sensitivity, and differential nuclease sensitivity data. Using simple t-tests to compute p-values across multiple datasets of different types, we evaluate iSeg using both simulated and experimental datasets and show that it performs satisfactorily when compared with some other popular methods, which often employ more sophisticated statistical models. Implemented in C++, iSeg is also very computationally efficient, well suited for large numbers of input profiles and data with very long sequences.

CONCLUSIONS: We have developed an efficient general-purpose segmentation tool and showed that it had comparable or more accurate results than many of the most popular segment-calling algorithms used in contemporary genomic data analysis. iSeg is capable of analyzing datasets that have both positive and negative values. Tunable parameters allow users to readily adjust the statistical stringency to best match the biological nature of individual datasets, including widely or sparsely mapped genomic datasets or those with non-normal distributions.}, } @article {pmid29642839, year = {2018}, author = {Farris, MH and Scott, AR and Texter, PA and Bartlett, M and Coleman, P and Masters, D}, title = {TIA: algorithms for development of identity-linked SNP islands for analysis by massively parallel DNA sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {126}, pmid = {29642839}, issn = {1471-2105}, support = {HSHQDC-14-D-00006//Science and Technology Directorate/International ; }, mesh = {*Algorithms ; DNA/genetics ; Genome, Human ; Genomic Islands/*genetics ; Haplotypes/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Polymorphism, Single Nucleotide/*genetics ; Reproducibility of Results ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Single nucleotide polymorphisms (SNPs) located within the human genome have been shown to have utility as markers of identity in the differentiation of DNA from individual contributors. Massively parallel DNA sequencing (MPS) technologies and human genome SNP databases allow for the design of suites of identity-linked target regions, amenable to sequencing in a multiplexed and massively parallel manner. Therefore, tools are needed for leveraging the genotypic information found within SNP databases for the discovery of genomic targets that can be evaluated on MPS platforms.

RESULTS: The SNP island target identification algorithm (TIA) was developed as a user-tunable system to leverage SNP information within databases. Using data within the 1000 Genomes Project SNP database, human genome regions were identified that contain globally ubiquitous identity-linked SNPs and that were responsive to targeted resequencing on MPS platforms. Algorithmic filters were used to exclude target regions that did not conform to user-tunable SNP island target characteristics. To validate the accuracy of TIA for discovering these identity-linked SNP islands within the human genome, SNP island target regions were amplified from 70 contributor genomic DNA samples using the polymerase chain reaction. Multiplexed amplicons were sequenced using the Illumina MiSeq platform, and the resulting sequences were analyzed for SNP variations. 166 putative identity-linked SNPs were targeted in the identified genomic regions. Of the 309 SNPs that provided discerning power across individual SNP profiles, 74 previously undefined SNPs were identified during evaluation of targets from individual genomes. Overall, DNA samples of 70 individuals were uniquely identified using a subset of the suite of identity-linked SNP islands.

CONCLUSIONS: TIA offers a tunable genome search tool for the discovery of targeted genomic regions that are scalable in the population frequency and numbers of SNPs contained within the SNP island regions. It also allows the definition of sequence length and sequence variability of the target region as well as the less variable flanking regions for tailoring to MPS platforms. As shown in this study, TIA can be used to discover identity-linked SNP islands within the human genome, useful for differentiating individuals by targeted resequencing on MPS technologies.}, } @article {pmid29642837, year = {2018}, author = {Thorne, T}, title = {Approximate inference of gene regulatory network models from RNA-Seq time series data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {127}, pmid = {29642837}, issn = {1471-2105}, mesh = {Algorithms ; Area Under Curve ; Bayes Theorem ; Cell Differentiation/genetics ; *Gene Regulatory Networks ; Humans ; *Models, Genetic ; Neural Stem Cells/*cytology ; ROC Curve ; Saccharomyces cerevisiae/*genetics ; Sequence Analysis, RNA/*methods ; Time Factors ; }, abstract = {BACKGROUND: Inference of gene regulatory network structures from RNA-Seq data is challenging due to the nature of the data, as measurements take the form of counts of reads mapped to a given gene. Here we present a model for RNA-Seq time series data that applies a negative binomial distribution for the observations, and uses sparse regression with a horseshoe prior to learn a dynamic Bayesian network of interactions between genes. We use a variational inference scheme to learn approximate posterior distributions for the model parameters.

RESULTS: The methodology is benchmarked on synthetic data designed to replicate the distribution of real world RNA-Seq data. We compare our method to other sparse regression approaches and find improved performance in learning directed networks. We demonstrate an application of our method to a publicly available human neuronal stem cell differentiation RNA-Seq time series data set to infer the underlying network structure.

CONCLUSIONS: Our method is able to improve performance on synthetic data by explicitly modelling the statistical distribution of the data when learning networks from RNA-Seq time series. Applying approximate inference techniques we can learn network structures quickly with only moderate computing resources.}, } @article {pmid29642836, year = {2018}, author = {Kumar, N and Hoque, MA and Sugimoto, M}, title = {Robust volcano plot: identification of differential metabolites in the presence of outliers.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {128}, pmid = {29642836}, issn = {1471-2105}, mesh = {Algorithms ; Biomarkers/metabolism ; Down-Regulation/genetics ; Female ; Humans ; *Metabolome ; Metabolomics/*methods ; ROC Curve ; Up-Regulation/genetics ; }, abstract = {BACKGROUND: The identification of differential metabolites in metabolomics is still a big challenge and plays a prominent role in metabolomics data analyses. Metabolomics datasets often contain outliers because of analytical, experimental, and biological ambiguity, but the currently available differential metabolite identification techniques are sensitive to outliers.

RESULTS: We propose a kernel weight based outlier-robust volcano plot for identifying differential metabolites from noisy metabolomics datasets. Two numerical experiments are used to evaluate the performance of the proposed technique against nine existing techniques, including the t-test and the Kruskal-Wallis test. Artificially generated data with outliers reveal that the proposed method results in a lower misclassification error rate and a greater area under the receiver operating characteristic curve compared with existing methods. An experimentally measured breast cancer dataset to which outliers were artificially added reveals that our proposed method produces only two non-overlapping differential metabolites whereas the other nine methods produced between seven and 57 non-overlapping differential metabolites.

CONCLUSION: Our data analyses show that the performance of the proposed differential metabolite identification technique is better than that of existing methods. Thus, the proposed method can contribute to analysis of metabolomics data with outliers. The R package and user manual of the proposed method are available at https://github.com/nishithkumarpaul/Rvolcano .}, } @article {pmid29642052, year = {2018}, author = {Tenconi, E and Rigali, S}, title = {Self-resistance mechanisms to DNA-damaging antitumor antibiotics in actinobacteria.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {100-108}, doi = {10.1016/j.mib.2018.03.003}, pmid = {29642052}, issn = {1879-0364}, abstract = {Streptomyces and few other Actinobacteria naturally produce compounds currently used in chemotherapy for being cytotoxic against various types of tumor cells by damaging the DNA structure and/or inhibiting DNA functions. DNA-damaging antitumor antibiotics belong to different classes of natural compounds that are structurally unrelated such as anthracyclines, bleomycins, enediynes, mitomycins, and prodiginines. By targeting a ubiquitous molecule and housekeeping functions, these compounds are also cytotoxic to their producer. How DNA-damaging antitumor antibiotics producing actinobacteria avoid suicide is the theme of the current review which illustrates the different strategies developed for self-resistance such as toxin sequestration, efflux, modification, destruction, target repair/protection, or stochastic activity. Finally, the observed spatio-temporal correlation between cell death, morphogenesis, and prodiginine production in S. coelicolor suggests a new physiological role for these molecules, that, together with their self-resistance mechanisms, would function as new types of toxin-antitoxin systems recruited in programmed cell death processes of the producer.}, } @article {pmid29641912, year = {2018}, author = {Jordan, DM and Do, R}, title = {Using Full Genomic Information to Predict Disease: Breaking Down the Barriers Between Complex and Mendelian Diseases.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {289-301}, doi = {10.1146/annurev-genom-083117-021136}, pmid = {29641912}, issn = {1545-293X}, support = {R35 GM124836/GM/NIGMS NIH HHS/United States ; }, abstract = {While sequence-based genetic tests have long been available for specific loci, especially for Mendelian disease, the rapidly falling costs of genome-wide genotyping arrays, whole-exome sequencing, and whole-genome sequencing are moving us toward a future where full genomic information might inform the prognosis and treatment of a variety of diseases, including complex disease. Similarly, the availability of large populations with full genomic information has enabled new insights about the etiology and genetic architecture of complex disease. Insights from the latest generation of genomic studies suggest that our categorization of diseases as complex may conceal a wide spectrum of genetic architectures and causal mechanisms that ranges from Mendelian forms of complex disease to complex regulatory structures underlying Mendelian disease. Here, we review these insights, along with advances in the prediction of disease risk and outcomes from full genomic information.}, } @article {pmid29641911, year = {2018}, author = {Williams, TN and Thein, SL}, title = {Sickle Cell Anemia and Its Phenotypes.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {113-147}, doi = {10.1146/annurev-genom-083117-021320}, pmid = {29641911}, issn = {1545-293X}, abstract = {In the 100 years since sickle cell anemia (SCA) was first described in the medical literature, studies of its molecular and pathophysiological basis have been at the vanguard of scientific discovery. By contrast, the translation of such knowledge into treatments that improve the lives of those affected has been much too slow. Recent years, however, have seen major advances on several fronts. A more detailed understanding of the switch from fetal to adult hemoglobin and the identification of regulators such as BCL11A provide hope that these findings will be translated into genomic-based approaches to the therapeutic reactivation of hemoglobin F production in patients with SCA. Meanwhile, an unprecedented number of new drugs aimed at both the treatment and prevention of end-organ damage are now in the pipeline, outcomes from potentially curative treatments such as allogeneic hematopoietic stem cell transplantation are improving, and great strides are being made in gene therapy, where methods employing both antisickling β-globin lentiviral vectors and gene editing are now entering clinical trials. Encouragingly, after a century of neglect, the profile of the vast majority of those with SCA in Africa and India is also finally improving.}, } @article {pmid29638211, year = {2018}, author = {Servín-Villegas, R and Caamal-Chan, MG and Chavez-Medina, A and Loera-Muro, A and Barraza, A and Medina-Hernández, D and Holguín-Peña, RJ}, title = {Identification of a 'Candidatus Phytoplasma hispanicum'-related strain, associated with yellows-type diseases, in smoke-tree sharpshooter (Homalodisca liturata Ball).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {2093-2101}, doi = {10.1099/ijsem.0.002745}, pmid = {29638211}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Hemiptera/*microbiology ; Mexico ; *Phylogeny ; Phytoplasma/*classification/genetics/isolation & purification ; Plant Diseases/*microbiology ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The 16SrXIII group from phytoplasma bacteria were identified in salivary glands from Homalodisca liturata, which were collected in El Comitán on the Baja California peninsula in Mexico. We were able to positively identify 15 16S rRNA gene sequences with the corresponding signature sequence of 'CandidatusPhytoplasma' (CAAGAYBATKATGTKTAGCYGGDCT) and in silico restriction fragment length polymorphism (RFLP) profiles (F value estimations) coupled with a phylogenetic analysis to confirm their relatedness to 'CandidatusPhytoplasma hispanicum', which in turn belongs to the 16SrXIII group. A restriction analysis was carried out with AluI and EcoRI to confirm that the five sequences belongs to subgroup D. The rest of the sequences did not exhibit any known RFLP profile related to a subgroup reported in the 16SrXIII group.}, } @article {pmid29638210, year = {2018}, author = {Weber, M and Schünemann, W and Fuß, J and Kämpfer, P and Lipski, A}, title = {Stenotrophomonas lactitubi sp. nov. and Stenotrophomonas indicatrix sp. nov., isolated from surfaces with food contact.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1830-1838}, doi = {10.1099/ijsem.0.002732}, pmid = {29638210}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Dairying/instrumentation ; Fatty Acids/chemistry ; *Food Microbiology ; Genes, Bacterial ; Germany ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Stenotrophomonas/*classification/genetics/isolation & purification ; }, abstract = {Five Gram-stain-negative, rod-shaped, none-spore-forming isolates were obtained from biofilms on different sites of a milking machine in Germany. Another strain with similar morphological characteristics was isolated from dirty dishes. Based on phylogenetic analysis of the 16S rRNA and gyrB genes, all isolates were assigned to the genus Stenotrophomonas, but were divided into three different groups. Chemotaxonomic characterization of the isolates led to the detection of iso-C15 : 0 and anteiso-C15 : 0 as the predominant cellular fatty acids, as well as small amounts of the hydroxyl fatty acids iso-C11 : 0 3-OH, C12 : 0 3-OH and iso-C13 : 0 3-OH. One group could be assigned to the species Stenotrophomonas maltophilia, while the genome sequences of two groups displayed average nucleotide identity values of less than 94 % between each other and the genome sequences of the next related type strains Stenotrophomonas maltophilia ATCC 13637T and Stenotrophomonas rhizophila DSM 14405T. Further phylogenetic, phenotypic and chemotaxonomic analyses enabled the differentiation of these strains from these closely related species. They are therefore considered to represent two novel species, for which the names Stenotrophomonaslactitubi and Stenotrophomonasindicatrix are proposed, with strains M15T (=DSM 104152T=LMG29943T) and WS40T (=DSM28278T=LMG29942T) as type strains.}, } @article {pmid29637226, year = {2018}, author = {Chen, N and Ling, ZX and Jin, TT and Li, M and Zhao, S and Zheng, LS and Xi, X and Wang, LL and Chen, YY and Shen, YL and Zhang, LP and Sun, SC}, title = {Altered Profiles of Gut Microbiota in Klebsiella pneumoniae-Induced Pyogenic Liver Abscess.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {952-959}, pmid = {29637226}, issn = {1432-0991}, support = {H2015201076//Natural Science Foundation of Hebei Province/ ; 81000760//National Natural Science Foundation of China/ ; 2014A2003//Medical Construction Special Project of Hebei University/ ; }, mesh = {Animals ; Bacteria/classification/genetics/*isolation & purification ; Biodiversity ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Humans ; Klebsiella Infections/*microbiology ; Klebsiella pneumoniae/*physiology ; Liver Abscess, Pyogenic/*microbiology ; Male ; Mice ; Mice, Inbred C57BL ; Phylogeny ; }, abstract = {Intestinal microbiota plays a crucial role in preventing the colonization and invasion by pathogens, and disruption of microbiota may cause opportunistic infections and diseases. Pathogens often have strategies to escape from the colonization resistance mediated by microbiota, but whether they also modulate the microbiota composition is still a topic of investigation. In the present study, we addressed this question using an opportunistic pathogen, Klebsiella pneumoniae serotype K1, which is known to cause pyogenic liver abscess (KLA) in about 30% of mice. We examined the effect of K. pneumoniae infection on cecal microbiota composition by performing high-throughput 454 pyrosequencing of the hypervariable V3-V4 regions of bacterial 16S rRNA gene. Our data revealed that K. pneumoniae inoculation substantially changed the cecal microbiota composition when analyzed at the phylum, order, and family levels. Most strikingly, the KLA-infected mice had significantly increased abundance of Bacteroidales and Enterobacteriales and decreased abundance of Lactobacillales and Eggerthellales. Furthermore, by comparing the infected mice with or without KLA disease symptoms, we identified specific microbiota changes associated with the KLA disease induction. Especially, the KLA group had dramatically decreased sequence identical to Lactobacillus compared with non-KLA mice. These findings suggest that the pathogenic process of KLA infection may involve alteration of microbiota compositions, particularly reduction in Lactobacillus.}, } @article {pmid29636805, year = {2018}, author = {Grear, DA and Hall, JS and Dusek, RJ and Ip, HS}, title = {Inferring epidemiologic dynamics from viral evolution: 2014-2015 Eurasian/North American highly pathogenic avian influenza viruses exceed transmission threshold, R0 = 1, in wild birds and poultry in North America.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {547-557}, pmid = {29636805}, issn = {1752-4571}, abstract = {Highly pathogenic avian influenza virus (HPAIV) is a multihost pathogen with lineages that pose health risks for domestic birds, wild birds, and humans. One mechanism of intercontinental HPAIV spread is through wild bird reservoirs, and wild birds were the likely sources of a Eurasian (EA) lineage HPAIV into North America in 2014. The introduction resulted in several reassortment events with North American (NA) lineage low-pathogenic avian influenza viruses and the reassortant EA/NA H5N2 went on to cause one of the largest HPAIV poultry outbreaks in North America. We evaluated three hypotheses about novel HPAIV introduced into wild and domestic bird hosts: (i) transmission of novel HPAIVs in wild birds was restricted by mechanisms associated with highly pathogenic phenotypes; (ii) the HPAIV poultry outbreak was not self-sustaining and required viral input from wild birds; and (iii) reassortment of the EA H5N8 generated reassortant EA/NA AIVs with a fitness advantage over fully Eurasian lineages in North American wild birds. We used a time-rooted phylodynamic model that explicitly incorporated viral population dynamics with evolutionary dynamics to estimate the basic reproductive number (R0) and viral migration among host types in domestic and wild birds, as well as between the EA H5N8 and EA/NA H5N2 in wild birds. We did not find evidence to support hypothesis (i) or (ii) as our estimates of the transmission parameters suggested that the HPAIV outbreak met or exceeded the threshold for persistence in wild birds (R0 > 1) and poultry (R0 ≈ 1) with minimal estimated transmission among host types. There was also no evidence to support hypothesis (iii) because R0 values were similar among EA H5N8 and EA/NA H5N2 in wild birds. Our results suggest that this novel HPAIV and reassortments did not encounter any transmission barriers sufficient to prevent persistence when introduced to wild or domestic birds.}, } @article {pmid29636804, year = {2018}, author = {Joseph, U and Vijaykrishna, D and Smith, GJD and Su, YCF}, title = {Adaptive evolution during the establishment of European avian-like H1N1 influenza A virus in swine.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {534-546}, pmid = {29636804}, issn = {1752-4571}, support = {HHSN272201400006C/AI/NIAID NIH HHS/United States ; }, abstract = {An H1N1 subtype influenza A virus with all eight gene segments derived from wild birds (including mallards), ducks and chickens, caused severe disease outbreaks in swine populations in Europe beginning in 1979 and successfully adapted to form the European avian-like swine (EA-swine) influenza lineage. Genes of the EA-swine lineage that are clearly segregated from its closest avian relatives continue to circulate in swine populations globally and represent a unique opportunity to study the adaptive process of an avian-to-mammalian cross-species transmission. Here, we used a relaxed molecular clock model to test whether the EA-swine virus originated through the introduction of a single avian ancestor as an entire genome, followed by an analysis of host-specific selection pressures among different gene segments. Our data indicated independent introduction of gene segments via transmission of avian viruses into swine followed by reassortment events that occurred at least 1-4 years prior to the EA-swine outbreak. All EA-swine gene segments exhibit greater selection pressure than avian viruses, reflecting both adaptive pressures and relaxed selective constraints that are associated with host switching. Notably, we identified key amino acid mutations in the viral surface proteins (H1 and N1) that play a role in adaptation to new hosts. Following the establishment of EA-swine lineage, we observed an increased frequency of intrasubtype reassortment of segments compared to the earlier strains that has been associated with adaptive amino acid replacements, disease severity and vaccine escape. Taken together, our study provides key insights into the adaptive changes in viral genomes following the transmission of avian influenza viruses to swine and the early establishment of the EA-swine lineage.}, } @article {pmid29636803, year = {2018}, author = {Lourenço, J and Tennant, W and Faria, NR and Walker, A and Gupta, S and Recker, M}, title = {Challenges in dengue research: A computational perspective.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {516-533}, pmid = {29636803}, issn = {1752-4571}, support = {//Wellcome Trust/United Kingdom ; 268904//European Research Council/International ; }, abstract = {The dengue virus is now the most widespread arbovirus affecting human populations, causing significant economic and social impact in South America and South-East Asia. Increasing urbanization and globalization, coupled with insufficient resources for control, misguided policies or lack of political will, and expansion of its mosquito vectors are some of the reasons why interventions have so far failed to curb this major public health problem. Computational approaches have elucidated on dengue's population dynamics with the aim to provide not only a better understanding of the evolution and epidemiology of the virus but also robust intervention strategies. It is clear, however, that these have been insufficient to address key aspects of dengue's biology, many of which will play a crucial role for the success of future control programmes, including vaccination. Within a multiscale perspective on this biological system, with the aim of linking evolutionary, ecological and epidemiological thinking, as well as to expand on classic modelling assumptions, we here propose, discuss and exemplify a few major computational avenues-real-time computational analysis of genetic data, phylodynamic modelling frameworks, within-host model frameworks and GPU-accelerated computing. We argue that these emerging approaches should offer valuable research opportunities over the coming years, as previously applied and demonstrated in the context of other pathogens.}, } @article {pmid29636802, year = {2018}, author = {Borlase, A and Webster, JP and Rudge, JW}, title = {Opportunities and challenges for modelling epidemiological and evolutionary dynamics in a multihost, multiparasite system: Zoonotic hybrid schistosomiasis in West Africa.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {501-515}, pmid = {29636802}, issn = {1752-4571}, abstract = {Multihost multiparasite systems are evolutionarily and ecologically dynamic, which presents substantial trans-disciplinary challenges for elucidating their epidemiology and designing appropriate control. Evidence for hybridizations and introgressions between parasite species is gathering, in part in line with improvements in molecular diagnostics and genome sequencing. One major system where this is becoming apparent is within the Genus Schistosoma, where schistosomiasis represents a disease of considerable medical and veterinary importance, the greatest burden of which occurs in sub-Saharan Africa. Interspecific hybridizations and introgressions bring an increased level of complexity over and above that already inherent within multihost, multiparasite systems, also representing an additional source of genetic variation that can drive evolution. This has the potential for profound implications for the control of parasitic diseases, including, but not exclusive to, widening host range, increased transmission potential and altered responses to drug therapy. Here, we present the challenging case example of haematobium group Schistosoma spp. hybrids in West Africa, a system involving multiple interacting parasites and multiple definitive hosts, in a region where zoonotic reservoirs of schistosomiasis were not previously considered to be of importance. We consider how existing mathematical model frameworks for schistosome transmission could be expanded and adapted to zoonotic hybrid systems, exploring how such model frameworks can utilize molecular and epidemiological data, as well as the complexities and challenges this presents. We also highlight the opportunities and value such mathematical models could bring to this and a range of similar multihost, multi and cross-hybridizing parasites systems in our changing world.}, } @article {pmid29636801, year = {2018}, author = {Viana, M and Faust, CL and Haydon, DT and Webster, JP and Lamberton, PHL}, title = {The effects of subcurative praziquantel treatment on life-history traits and trade-offs in drug-resistant Schistosoma mansoni.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {488-500}, pmid = {29636801}, issn = {1752-4571}, abstract = {Natural selection acts on all organisms, including parasites, to maximize reproductive fitness. Drug resistance traits are often associated with life-history costs in the absence of treatment. Schistosomiasis control programmes rely on mass drug administration to reduce human morbidity and mortality. Although hotspots of reduced drug efficacy have been reported, resistance is not widespread. Using Bayesian state-space models (SSMs) fitted to data from an in vivo laboratory system, we tested the hypothesis that the spread of resistant Schistosoma mansoni may be limited by life-history costs not present in susceptible counterparts. S. mansoni parasites from a praziquantel-susceptible (S), a praziquantel-resistant (R) or a mixed line of originally resistant and susceptible parasites (RS) were exposed to a range of praziquantel doses. Parasite numbers at each life stage were quantified in their molluscan intermediate and murine definitive hosts across four generations, and SSMs were used to estimate key life-history parameters for each experimental group over time. Model outputs illustrated that parasite adult survival and fecundity in the murine host decreased across all lines, including R, with increasing drug pressure. Trade-offs between adult survival and fecundity were observed in all untreated lines, and these remained strong in S with praziquantel pressure. In contrast, trade-offs between adult survival and fecundity were lost under praziquantel pressure in R. As expected, parasite life-history traits within the molluscan host were complex, but trade-offs were demonstrated between parasite establishment and cercarial output. The observed trade-offs between generations within hosts, which were modified by praziquantel treatment in the R line, could limit the spread of R parasites under praziquantel pressure. Whilst such complex life-history costs may be difficult to detect using standard empirical methods, we demonstrate that SSMs provide robust estimates of life-history parameters, aiding our understanding of costs and trade-offs of resistant parasites within this system and beyond.}, } @article {pmid29636800, year = {2018}, author = {Flores-Ferrer, A and Marcou, O and Waleckx, E and Dumonteil, E and Gourbière, S}, title = {Evolutionary ecology of Chagas disease; what do we know and what do we need?.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {470-487}, pmid = {29636800}, issn = {1752-4571}, abstract = {The aetiological agent of Chagas disease, Trypanosoma cruzi, is a key human pathogen afflicting most populations of Latin America. This vectorborne parasite is transmitted by haematophageous triatomines, whose control by large-scale insecticide spraying has been the main strategy to limit the impact of the disease for over 25 years. While those international initiatives have been successful in highly endemic areas, this systematic approach is now challenged by the emergence of insecticide resistance and by its low efficacy in controlling species that are only partially adapted to human habitat. In this contribution, we review evidences that Chagas disease control shall now be entering a second stage that will rely on a better understanding of triatomines adaptive potential, which requires promoting microevolutionary studies and -omic approaches. Concomitantly, we show that our knowledge of the determinants of the evolution of T. cruzi high diversity and low virulence remains too limiting to design evolution-proof strategies, while such attributes may be part of the future of Chagas disease control after the 2020 WHO's target of regional elimination of intradomiciliary transmission has been reached. We should then aim at developing a theory of T. cruzi virulence evolution that we anticipate to provide an interesting enrichment of the general theory according to the specificities of transmission of this very generalist stercorarian trypanosome. We stress that many ecological data required to better understand selective pressures acting on vector and parasite populations are already available as they have been meticulously accumulated in the last century of field research. Although more specific information will surely be needed, an effective research strategy would be to integrate data into the conceptual and theoretical framework of evolutionary ecology and life-history evolution that provide the quantitative backgrounds necessary to understand and possibly anticipate adaptive responses to public health interventions.}, } @article {pmid29636799, year = {2018}, author = {Lefevre, T and Ohm, J and Dabiré, KR and Cohuet, A and Choisy, M and Thomas, MB and Cator, L}, title = {Transmission traits of malaria parasites within the mosquito: Genetic variation, phenotypic plasticity, and consequences for control.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {456-469}, pmid = {29636799}, issn = {1752-4571}, abstract = {Evaluating the risk of emergence and transmission of vector-borne diseases requires knowledge of the genetic and environmental contributions to pathogen transmission traits. Compared to the significant effort devoted to understanding the biology of malaria transmission from vertebrate hosts to mosquito vectors, the strategies that malaria parasites have evolved to maximize transmission from vectors to vertebrate hosts have been largely overlooked. While determinants of infection success within the mosquito host have recently received attention, the causes of variability for other key transmission traits of malaria, namely the duration of parasite development and its virulence within the vector, as well as its ability to alter mosquito behavior, remain largely unknown. This important gap in our knowledge needs to be bridged in order to obtain an integrative view of the ecology and evolution of malaria transmission strategies. Associations between transmission traits also need to be characterized, as they trade-offs and constraints could have important implications for understanding the evolution of parasite transmission. Finally, theoretical studies are required to evaluate how genetic and environmental influences on parasite transmission traits can shape malaria dynamics and evolution in response to disease control.}, } @article {pmid29636798, year = {2018}, author = {Birget, PLG and Greischar, MA and Reece, SE and Mideo, N}, title = {Altered life history strategies protect malaria parasites against drugs.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {442-455}, pmid = {29636798}, issn = {1752-4571}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Drug resistance has been reported against all antimalarial drugs, and while parasites can evolve classical resistance mechanisms (e.g., efflux pumps), it is also possible that changes in life history traits could help parasites evade the effects of treatment. The life history of malaria parasites is governed by an intrinsic resource allocation problem: specialized stages are required for transmission, but producing these stages comes at the cost of producing fewer of the forms required for within-host survival. Drug treatment, by design, alters the probability of within-host survival, and so should alter the costs and benefits of investing in transmission. Here, we use a within-host model of malaria infection to predict optimal patterns of investment in transmission in the face of different drug treatment regimes and determine the extent to which alternative patterns of investment can buffer the fitness loss due to drugs. We show that over a range of drug doses, parasites are predicted to adopt "reproductive restraint" (investing more in asexual replication and less in transmission) to maximize fitness. By doing so, parasites recoup some of the fitness loss imposed by drugs, though as may be expected, increasing dose reduces the extent to which altered patterns of transmission investment can benefit parasites. We show that adaptation to drug-treated infections could result in more virulent infections in untreated hosts. This work emphasizes that in addition to classical resistance mechanisms, drug treatment generates selection for altered parasite life history. Understanding how any shifts in life history will alter the efficacy of drugs, as well as any limitations on such shifts, is important for evaluating and predicting the consequences of drug treatment.}, } @article {pmid29636797, year = {2018}, author = {Glunt, KD and Coetzee, M and Huijben, S and Koffi, AA and Lynch, PA and N'Guessan, R and Oumbouke, WA and Sternberg, ED and Thomas, MB}, title = {Empirical and theoretical investigation into the potential impacts of insecticide resistance on the effectiveness of insecticide-treated bed nets.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {431-441}, pmid = {29636797}, issn = {1752-4571}, support = {R21 AI113609/AI/NIAID NIH HHS/United States ; }, abstract = {In spite of widespread insecticide resistance in vector mosquitoes throughout Africa, there is limited evidence that long-lasting insecticidal bed nets (LLINs) are failing to protect against malaria. Here, we showed that LLIN contact in the course of host-seeking resulted in higher mortality of resistant Anopheles spp. mosquitoes than predicted from standard laboratory exposures with the same net. We also found that sublethal contact with an LLIN caused a reduction in blood feeding and subsequent host-seeking success in multiple lines of resistant mosquitoes from the laboratory and the field. Using a transmission model, we showed that when these LLIN-related lethal and sublethal effects were accrued over mosquito lifetimes, they greatly reduced the impact of resistance on malaria transmission potential under conditions of high net coverage. If coverage falls, the epidemiological impact is far more pronounced. Similarly, if the intensity of resistance intensifies, the loss of malaria control increases nonlinearly. Our findings help explain why insecticide resistance has not yet led to wide-scale failure of LLINs, but reinforce the call for alternative control tools and informed resistance management strategies.}, } @article {pmid29636796, year = {2018}, author = {Huijben, S and Paaijmans, KP}, title = {Putting evolution in elimination: Winning our ongoing battle with evolving malaria mosquitoes and parasites.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {415-430}, pmid = {29636796}, issn = {1752-4571}, abstract = {Since 2000, the world has made significant progress in reducing malaria morbidity and mortality, and several countries in Africa, South America and South-East Asia are working hard to eliminate the disease. These elimination efforts continue to rely heavily on antimalarial drugs and insecticide-based interventions, which remain the cornerstones of malaria treatment and prevention. However, resistance has emerged against nearly every antimalarial drug and insecticide that is available. In this review we discuss the evolutionary consequences of the way we currently implement antimalarial interventions, which is leading to resistance and may ultimately lead to control failure, but also how evolutionary principles can be applied to extend the lifespan of current and novel interventions. A greater understanding of the general evolutionary principles that are at the core of emerging resistance is urgently needed if we are to develop improved resistance management strategies with the ultimate goal to achieve a malaria-free world.}, } @article {pmid29636795, year = {2018}, author = {Sternberg, ED and Thomas, MB}, title = {Insights from agriculture for the management of insecticide resistance in disease vectors.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {404-414}, pmid = {29636795}, issn = {1752-4571}, support = {R21 AI113609/AI/NIAID NIH HHS/United States ; }, abstract = {Key to contemporary management of diseases such as malaria, dengue, and filariasis is control of the insect vectors responsible for transmission. Insecticide-based interventions have contributed to declines in disease burdens in many areas, but this progress could be threatened by the emergence of insecticide resistance in vector populations. Insecticide resistance is likewise a major concern in agriculture, where insect pests can cause substantial yield losses. Here, we explore overlaps between understanding and managing insecticide resistance in agriculture and in public health. We have used the Global Plan for Insecticide Resistance Management in malaria vectors, developed under the auspices of the World Health Organization Global Malaria Program, as a framework for this exploration because it serves as one of the few cohesive documents for managing a global insecticide resistance crisis. Generally, this comparison highlights some fundamental differences between insect control in agriculture and in public health. Moreover, we emphasize that the success of insecticide resistance management strategies is strongly dependent on the biological specifics of each system. We suggest that the biological, operational, and regulatory differences between agriculture and public health limit the wholesale transfer of knowledge and practices from one system to the other. Nonetheless, there are some valuable insights from agriculture that could assist in advancing the existing Global Plan for Insecticide Resistance Management framework.}, } @article {pmid29636794, year = {2018}, author = {Kosoy, M and Kosoy, R}, title = {Complexity and biosemiotics in evolutionary ecology of zoonotic infectious agents.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {394-403}, pmid = {29636794}, issn = {1752-4571}, abstract = {More is not automatically better. Generation and accumulation of information reflecting the complexity of zoonotic diseases as ecological systems do not necessarily lead to improved interpretation of the obtained information and understanding of these complex systems. The traditional conceptual framework for analysis of diseases ecology is neither designed for, nor adaptable enough, to absorb the mass of diverse sources of relevant information. The multidirectional and multidimensional approaches to analyses form an inevitable part in defining a role of zoonotic pathogens and animal hosts considering the complexity of their inter-relations. And the more data we have, the more involved the interpretation needs to be. The keyword for defining the roles of microbes as pathogens, animals as hosts, and environmental parameters as infection drivers is "functional importance." Microbes can act as pathogens toward their host only if/when they recognize the animal organism as the target. The same is true when the host recognizes the microbe as a pathogen rather than harmless symbiont based on the context of its occurrence in that host. Here, we propose conceptual tools developed in the realm of the interdisciplinary sciences of complexity and biosemiotics for extending beyond the currently dominant mindset in ecology and evolution of infectious diseases. We also consider four distinct hierarchical levels of perception guiding how investigators can approach zoonotic agents, as a subject of their research, representing differences in emphasizing particular elements and their relations versus more unified systemic approaches.}, } @article {pmid29636793, year = {2018}, author = {Echaubard, P and Rudge, JW and Lefevre, T}, title = {Evolutionary perspectives on human infectious diseases: Challenges, advances, and promises.}, journal = {Evolutionary applications}, volume = {11}, number = {4}, pages = {383-393}, pmid = {29636793}, issn = {1752-4571}, } @article {pmid29636579, year = {2018}, author = {}, title = {Planet of the microorganisms.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {257}, doi = {10.1038/nrmicro.2018.38}, pmid = {29636579}, issn = {1740-1534}, } @article {pmid29636578, year = {2018}, author = {Mak, KF and Shan, J}, title = {Mirrors made of a single atomic layer.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {177-178}, doi = {10.1038/d41586-018-04089-1}, pmid = {29636578}, issn = {1476-4687}, } @article {pmid29636577, year = {2018}, author = {Aggarwal, A}, title = {Demand cancer drugs that truly help patients.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {151}, doi = {10.1038/d41586-018-04154-9}, pmid = {29636577}, issn = {1476-4687}, mesh = {Antineoplastic Agents ; *Health Policy ; *Health Services Needs and Demand ; Humans ; }, } @article {pmid29636576, year = {2018}, author = {Else, H}, title = {Science's vast gender pay gap revealed in UK wage data.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {160}, doi = {10.1038/d41586-018-04309-8}, pmid = {29636576}, issn = {1476-4687}, mesh = {Drug Industry ; Research Personnel/*economics/*supply & distribution ; Salaries and Fringe Benefits/economics/*statistics & numerical data ; *Science/economics ; *Sex Factors ; Sexism/economics/*statistics & numerical data ; United Kingdom ; Universities ; Workforce ; }, } @article {pmid29636575, year = {2018}, author = {Zaret, KS}, title = {The telomerase enzyme and liver renewal.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {181-182}, doi = {10.1038/d41586-018-02684-w}, pmid = {29636575}, issn = {1476-4687}, mesh = {Liver ; Liver Regeneration ; Telomerase/*genetics ; *Telomere ; }, } @article {pmid29636574, year = {2018}, author = {Ledford, H}, title = {Cutting-edge cancer drug hobbled by diagnostic test confusion.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {161-162}, doi = {10.1038/d41586-018-03862-6}, pmid = {29636574}, issn = {1476-4687}, mesh = {Antibodies, Monoclonal, Humanized/immunology/*therapeutic use ; Antineoplastic Agents/immunology/*therapeutic use ; Biomarkers, Tumor/metabolism ; DNA Repair/genetics ; Drug Approval/legislation & jurisprudence ; Genes, BRCA1 ; Genes, BRCA2 ; Humans ; Melanoma/drug therapy/immunology ; Neoplasms/*diagnosis/*drug therapy/genetics/immunology ; United States ; United States Food and Drug Administration/legislation & jurisprudence ; }, } @article {pmid29636573, year = {2018}, author = {}, title = {How a chicken makes a good egg.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {152}, doi = {10.1038/d41586-018-04087-3}, pmid = {29636573}, issn = {1476-4687}, } @article {pmid29636572, year = {2018}, author = {Witze, A}, title = {NASA's next exoplanet hunter will seek worlds close to home.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {158-159}, doi = {10.1038/d41586-018-03354-7}, pmid = {29636572}, issn = {1476-4687}, } @article {pmid29636571, year = {2018}, author = {Guglielmi, G}, title = {Plan to dismantle Puerto Rico's statistics agency gets green light.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {161}, doi = {10.1038/d41586-018-04120-5}, pmid = {29636571}, issn = {1476-4687}, mesh = {Cyclonic Storms/mortality ; Data Collection/*economics/*standards ; Government Agencies/*economics/*organization & administration ; Humans ; Puerto Rico ; }, } @article {pmid29636570, year = {2018}, author = {Cyranoski, D}, title = {Beijing launches pioneering brain-science centre.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {157-158}, doi = {10.1038/d41586-018-04122-3}, pmid = {29636570}, issn = {1476-4687}, mesh = {Academies and Institutes/*organization & administration ; Beijing ; Biomedical Research/organization & administration ; *Brain/physiology ; Humans ; Neurosciences/education/*organization & administration ; Personnel Selection ; Workforce ; }, } @article {pmid29636569, year = {2018}, author = {}, title = {A squid-skin-inspired invisibility cloak.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {153}, doi = {10.1038/d41586-018-04009-3}, pmid = {29636569}, issn = {1476-4687}, } @article {pmid29636568, year = {2018}, author = {}, title = {Dexterous sea turtles use flippers as grippers.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {153}, doi = {10.1038/d41586-018-04108-1}, pmid = {29636568}, issn = {1476-4687}, } @article {pmid29636567, year = {2018}, author = {}, title = {An absorbing study on the maths of sponges.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {153}, doi = {10.1038/d41586-018-04010-w}, pmid = {29636567}, issn = {1476-4687}, } @article {pmid29636566, year = {2018}, author = {}, title = {Jekyll and Hyde, a story of two galaxies.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {152}, doi = {10.1038/d41586-018-04062-y}, pmid = {29636566}, issn = {1476-4687}, } @article {pmid29636565, year = {2018}, author = {}, title = {A chance to save Arctic sea ice.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {152}, doi = {10.1038/d41586-018-04063-x}, pmid = {29636565}, issn = {1476-4687}, } @article {pmid29636564, year = {2018}, author = {}, title = {Why fat piles on when the body's daily cycles are in disarray.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {153}, doi = {10.1038/d41586-018-04261-7}, pmid = {29636564}, issn = {1476-4687}, } @article {pmid29636563, year = {2018}, author = {}, title = {Mice show motherly habits when a brain circuit fires.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {153}, doi = {10.1038/d41586-018-04109-0}, pmid = {29636563}, issn = {1476-4687}, } @article {pmid29636562, year = {2018}, author = {Savage, N}, title = {Collaboration is the key to cancer research.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {S1-S3}, doi = {10.1038/d41586-018-04164-7}, pmid = {29636562}, issn = {1476-4687}, mesh = {Algorithms ; Biomedical Research/economics/*organization & administration ; Communication ; Computational Biology/organization & administration ; Conflict (Psychology) ; *Cooperative Behavior ; Goals ; Group Processes ; Humans ; Interdisciplinary Research/economics/*organization & administration ; National Cancer Institute (U.S.)/organization & administration ; *Neoplasms/drug therapy/genetics ; Research Personnel/economics/*organization & administration/psychology ; United States ; Workforce ; }, } @article {pmid29636561, year = {2018}, author = {May, M}, title = {Cancer research with a human touch.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {259-261}, doi = {10.1038/d41586-018-04161-w}, pmid = {29636561}, issn = {1476-4687}, mesh = {Animals ; Biomedical Research/*methods/standards ; Cell Line, Tumor ; Clinical Trials as Topic/methods/standards ; *Disease Models, Animal ; Disease Progression ; *Gene Editing ; Humans ; Neoplasms/*genetics/immunology/pathology ; Reproducibility of Results ; Translational Medical Research/*methods/standards ; *Xenograft Model Antitumor Assays ; }, } @article {pmid29636559, year = {2018}, author = {}, title = {A molecule that manufactures asymmetry.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {152-153}, doi = {10.1038/d41586-018-04256-4}, pmid = {29636559}, issn = {1476-4687}, } @article {pmid29636558, year = {2018}, author = {Paola Zambetti, L}, title = {Convert your weaknesses into assets.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {265}, doi = {10.1038/d41586-018-04162-9}, pmid = {29636558}, issn = {1476-4687}, } @article {pmid29636557, year = {2018}, author = {Pironio, S}, title = {The certainty of randomness.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {176-177}, doi = {10.1038/d41586-018-04105-4}, pmid = {29636557}, issn = {1476-4687}, } @article {pmid29636556, year = {2018}, author = {Praetorius, SK}, title = {North Atlantic circulation slows down.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {180-181}, doi = {10.1038/d41586-018-04086-4}, pmid = {29636556}, issn = {1476-4687}, mesh = {Atlantic Ocean ; *Climate ; Seawater ; Temperature ; *Water Movements ; }, } @article {pmid29636426, year = {2018}, author = {Tullos, D}, title = {Opinion: How to achieve better flood-risk governance in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3731-3734}, pmid = {29636426}, issn = {1091-6490}, mesh = {*Disaster Planning ; Disasters/*prevention & control ; *Floods ; *Government Agencies ; Humans ; *Public Opinion ; *Public Policy ; Risk Management ; United States ; }, } @article {pmid29636421, year = {2018}, author = {Dong, Q and Li, X and Wang, CZ and Xu, S and Yuan, G and Shao, W and Liu, B and Zheng, Y and Wang, H and Lei, X and Zhang, Z and Zhu, B}, title = {Roles of the CSE1L-mediated nuclear import pathway in epigenetic silencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4013-E4022}, pmid = {29636421}, issn = {1091-6490}, mesh = {Active Transport, Cell Nucleus/drug effects/genetics ; Cell Line ; Cell Nucleus/genetics/*metabolism ; Cellular Apoptosis Susceptibility Protein/genetics/*metabolism ; DNA Methylation/drug effects ; Gene Silencing/drug effects/*physiology ; Genome-Wide Association Study ; Histone Deacetylase 1/genetics/metabolism ; Histone Deacetylase 2/genetics/metabolism ; Histone Deacetylase Inhibitors/pharmacology ; Histone Deacetylases/genetics/metabolism ; Humans ; RNA-Binding Proteins/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; beta Karyopherins/genetics/metabolism ; }, abstract = {Epigenetic silencing can be mediated by various mechanisms, and many regulators remain to be identified. Here, we report a genome-wide siRNA screening to identify regulators essential for maintaining gene repression of a CMV promoter silenced by DNA methylation. We identified CSE1L (chromosome segregation 1 like) as an essential factor for the silencing of the reporter gene and many endogenous methylated genes. CSE1L depletion did not cause DNA demethylation. On the other hand, the methylated genes derepressed by CSE1L depletion largely overlapped with methylated genes that were also reactivated by treatment with histone deacetylase inhibitors (HDACi). Gene silencing defects observed upon CSE1L depletion were linked to its nuclear import function for certain protein cargos because depletion of other factors involved in the same nuclear import pathway, including KPNAs and KPNB1 proteins, displayed similar derepression profiles at the genome-wide level. Therefore, CSE1L appears to be critical for the nuclear import of certain key repressive proteins. Indeed, NOVA1, HDAC1, HDAC2, and HDAC8, genes known as silencing factors, became delocalized into cytosol upon CSE1L depletion. This study suggests that the cargo specificity of the protein nuclear import system may impact the selectivity of gene silencing.}, } @article {pmid29636420, year = {2018}, author = {Vavrek, JR and Henderson, BS and Danagoulian, A}, title = {Experimental demonstration of an isotope-sensitive warhead verification technique using nuclear resonance fluorescence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4363-4368}, pmid = {29636420}, issn = {1091-6490}, abstract = {Future nuclear arms reduction efforts will require technologies to verify that warheads slated for dismantlement are authentic without revealing any sensitive weapons design information to international inspectors. Despite several decades of research, no technology has met these requirements simultaneously. Recent work by Kemp et al. [Kemp RS, Danagoulian A, Macdonald RR, Vavrek JR (2016) Proc Natl Acad Sci USA 113:8618-8623] has produced a novel physical cryptographic verification protocol that approaches this treaty verification problem by exploiting the isotope-specific nature of nuclear resonance fluorescence (NRF) measurements to verify the authenticity of a warhead. To protect sensitive information, the NRF signal from the warhead is convolved with that of an encryption foil that contains key warhead isotopes in amounts unknown to the inspector. The convolved spectrum from a candidate warhead is statistically compared against that from an authenticated template warhead to determine whether the candidate itself is authentic. Here we report on recent proof-of-concept warhead verification experiments conducted at the Massachusetts Institute of Technology. Using high-purity germanium (HPGe) detectors, we measured NRF spectra from the interrogation of proxy "genuine" and "hoax" objects by a 2.52 MeV endpoint bremsstrahlung beam. The observed differences in NRF intensities near 2.2 MeV indicate that the physical cryptographic protocol can distinguish between proxy genuine and hoax objects with high confidence in realistic measurement times.}, } @article {pmid29636419, year = {2018}, author = {Huang, R and Han, M and Meng, L and Chen, X}, title = {Transcriptome-wide discovery of coding and noncoding RNA-binding proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3879-E3887}, pmid = {29636419}, issn = {1091-6490}, mesh = {*Gene Expression Profiling ; HEK293 Cells ; HeLa Cells ; Humans ; RNA-Binding Proteins/genetics/*metabolism ; Transcriptome/*physiology ; }, abstract = {Transcriptome-wide identification of RNA-binding proteins (RBPs) is a prerequisite for understanding the posttranscriptional gene regulation networks. However, proteomic profiling of RBPs has been mostly limited to polyadenylated mRNA-binding proteins, leaving RBPs on nonpoly(A) RNAs, including most noncoding RNAs (ncRNAs) and pre-mRNAs, largely undiscovered. Here we present a click chemistry-assisted RNA interactome capture (CARIC) strategy, which enables unbiased identification of RBPs, independent of the polyadenylation state of RNAs. CARIC combines metabolic labeling of RNAs with an alkynyl uridine analog and in vivo RNA-protein photocross-linking, followed by click reaction with azide-biotin, affinity enrichment, and proteomic analysis. Applying CARIC, we identified 597 RBPs in HeLa cells, including 130 previously unknown RBPs. These newly discovered RBPs can likely bind ncRNAs, thus uncovering potential involvement of ncRNAs in processes previously unknown to be ncRNA-related, such as proteasome function and intermediary metabolism. The CARIC strategy should be broadly applicable across various organisms to complete the census of RBPs.}, } @article {pmid29636418, year = {2018}, author = {Männikkö, R and Shenkarev, ZO and Thor, MG and Berkut, AA and Myshkin, MY and Paramonov, AS and Kulbatskii, DS and Kuzmin, DA and Sampedro Castañeda, M and King, L and Wilson, ER and Lyukmanova, EN and Kirpichnikov, MP and Schorge, S and Bosmans, F and Hanna, MG and Kullmann, DM and Vassilevski, AA}, title = {Spider toxin inhibits gating pore currents underlying periodic paralysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4495-4500}, pmid = {29636418}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 NS091352/NS/NINDS NIH HHS/United States ; MR/M006948/1//Medical Research Council/United Kingdom ; }, mesh = {Amino Acid Substitution ; Animals ; Female ; HEK293 Cells ; Humans ; Ion Channel Gating ; *Mutation, Missense ; NAV1.4 Voltage-Gated Sodium Channel/chemistry/genetics/*metabolism ; Neurotoxins/*toxicity ; Paralysis, Hyperkalemic Periodic/genetics/*metabolism/pathology ; *Protein Structure, Secondary ; Spider Venoms/*toxicity ; Xenopus laevis ; }, abstract = {Gating pore currents through the voltage-sensing domains (VSDs) of the skeletal muscle voltage-gated sodium channel NaV1.4 underlie hypokalemic periodic paralysis (HypoPP) type 2. Gating modifier toxins target ion channels by modifying the function of the VSDs. We tested the hypothesis that these toxins could function as blockers of the pathogenic gating pore currents. We report that a crab spider toxin Hm-3 from Heriaeus melloteei can inhibit gating pore currents due to mutations affecting the second arginine residue in the S4 helix of VSD-I that we have found in patients with HypoPP and describe here. NMR studies show that Hm-3 partitions into micelles through a hydrophobic cluster formed by aromatic residues and reveal complex formation with VSD-I through electrostatic and hydrophobic interactions with the S3b helix and the S3-S4 extracellular loop. Our data identify VSD-I as a specific binding site for neurotoxins on sodium channels. Gating modifier toxins may constitute useful hits for the treatment of HypoPP.}, } @article {pmid29636417, year = {2018}, author = {Garcia-Guerrero, MC and Garcia-Pardo, J and Berenguer, E and Fernandez-Alvarez, R and Barfi, GB and Lyons, PJ and Aviles, FX and Huber, R and Lorenzo, J and Reverter, D}, title = {Crystal structure and mechanism of human carboxypeptidase O: Insights into its specific activity for acidic residues.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3932-E3939}, pmid = {29636417}, issn = {1091-6490}, mesh = {Carboxypeptidases/*chemistry/metabolism ; Catalytic Domain ; Crystallography, X-Ray ; Humans ; Pancreas/*enzymology ; Protease Inhibitors/*chemistry ; Substrate Specificity ; }, abstract = {Human metallocarboxypeptidase O (hCPO) is a recently discovered digestive enzyme localized to the apical membrane of intestinal epithelial cells. Unlike pancreatic metallocarboxypeptidases, hCPO is glycosylated and produced as an active enzyme with distinctive substrate specificity toward C-terminal (C-t) acidic residues. Here we present the crystal structure of hCPO at 1.85-Å resolution, both alone and in complex with a carboxypeptidase inhibitor (NvCI) from the marine snail Nerita versicolor The structure provides detailed information regarding determinants of enzyme specificity, in particular Arg275, placed at the bottom of the substrate-binding pocket. This residue, located at "canonical" position 255, where it is Ile in human pancreatic carboxypeptidases A1 (hCPA1) and A2 (hCPA2) and Asp in B (hCPB), plays a dominant role in determining the preference of hCPO for acidic C-t residues. Site-directed mutagenesis to Asp and Ala changes the specificity to C-t basic and hydrophobic residues, respectively. The single-site mutants thus faithfully mimic the enzymatic properties of CPB and CPA, respectively. hCPO also shows a preference for Glu over Asp, probably as a consequence of a tighter fitting of the Glu side chain in its S1' substrate-binding pocket. This unique preference of hCPO, together with hCPA1, hCPA2, and hCPB, completes the array of C-t cleavages enabling the digestion of the dietary proteins within the intestine. Finally, in addition to activity toward small synthetic substrates and peptides, hCPO can also trim C-t extensions of proteins, such as epidermal growth factor, suggesting a role in the maturation and degradation of growth factors and bioactive peptides.}, } @article {pmid29636189, year = {2018}, author = {Reichardt, JKV}, title = {Reflections of a Biomedical Scientist on Four Continents in Interdisciplinary Research.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {6}, pages = {401-403}, doi = {10.1016/j.tig.2018.03.004}, pmid = {29636189}, issn = {0168-9525}, } @article {pmid29636100, year = {2018}, author = {Baidoo, PK and Baddoo, D and Ocloo, A and Agbley, D and Lartey, S and Baddoo, NA}, title = {Tuberculous tenosynovitis of the flexor tendons of the wrist: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {238}, pmid = {29636100}, issn = {1756-0500}, mesh = {Aged ; Female ; Humans ; Tenosynovitis/*diagnosis ; Tuberculosis, Osteoarticular/*diagnosis ; Wrist Joint/*pathology ; }, abstract = {BACKGROUND: Tuberculous tenosynovitis poses a significant public health challenge, especially in developing countries. It usually affects the flexor tendons of the wrist.

CASE PRESENTATION: We present a case of a 65-year-old Ghanaian female. She presented a progressively enlarging mass over the volar aspect of the right wrist and palm. She did not have a previous history of tuberculosis. However, her erythrocyte sedimentation rate was high and Mantoux (purified protein derivative) test was strongly positive (more than 15 mm). Radiograph of ulna, radius, and wrist showed osteopenic changes around the distal radius. Excision biopsy of the mass was done and samples sent for histopathology comment. The findings were an inflamed, thickened synovia with rice bodies: suggestive of tuberculous tenosynovitis. Anti-tuberculous chemotherapy was commenced on the second postoperative day.

CONCLUSION: Tuberculous tenosynovitis of the wrist is uncommon. However, in developing countries like Ghana where tuberculosis is prevalent, it should be part of the differential diagnosis of compound palmar ganglion in order to prevent delayed diagnosis and treatment.}, } @article {pmid29636094, year = {2018}, author = {Campos, P and Guivernau, M and Prenafeta-Boldú, FX and Cardona, L}, title = {Fast acquisition of a polysaccharide fermenting gut microbiome by juvenile green turtles Chelonia mydas after settlement in coastal habitats.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {69}, pmid = {29636094}, issn = {2049-2618}, support = {235186/2014-7//CNPq- Conselho Nacional de Desenvolvimento Científico e Tecnológico - Brasil/International ; }, mesh = {Animals ; Biodiversity ; Brazil ; *Ecosystem ; *Fermentation ; *Gastrointestinal Microbiome ; Polysaccharides/*metabolism ; Turtles/*metabolism ; }, abstract = {BACKGROUND: Tetrapods do not express hydrolases for cellulose and hemicellulose assimilation, and hence, the independent acquisition of herbivory required the establishment of new endosymbiotic relationships between tetrapods and microbes. Green turtles (Chelonia mydas) are one of the three groups of marine tetrapods with an herbivorous diet and which acquire it after several years consuming pelagic animals. We characterized the microbiota present in the feces and rectum of 24 young wild and captive green turtles from the coastal waters of Brazil, with curved carapace length ranging from 31.1 to 64.7 cm, to test the hypotheses that (1) the ontogenetic dietary shift after settlement is followed by a gradual change in the composition and diversity of the gut microbiome, (2) differences exist between the composition and diversity of the gut microbiome of green turtles from tropical and subtropical regions, and (3) the consumption of omnivorous diets modifies the gut microbiota of green turtles.

RESULTS: A genomic library of 2,186,596 valid bacterial 16S rRNA reads was obtained and these sequences were grouped into 6321 different operational taxonomic units (at 97% sequence homology cutoff). The results indicated that most of the juvenile green turtles less than 45 cm of curved carapace length exhibited a fecal microbiota co-dominated by representatives of the phyla Bacteroidetes and Firmicutes and high levels of Clostridiaceae, Prophyromonas, Ruminococaceae, and Lachnospiraceae within the latter phylum. Furthermore, this was the only microbiota profile found in wild green turtles > 45 cm CCL and in most of the captive green turtles of any size feeding on a macroalgae/fish mixed diet. Nevertheless, microbial diversity increased with turtle size and was higher in turtles from tropical than from subtropical regions.

CONCLUSIONS: These results indicate that juvenile green turtles from the coastal waters of Brazil had the same general microbiota, regardless of body size and origin, and suggest a fast acquisition of a polysaccharide fermenting gut microbiota by juvenile green turtles after settlement into coastal habitats.}, } @article {pmid29636087, year = {2018}, author = {Wijethunga, WMUA and Dissanayake, HA and Perera, S and Katulanda, P}, title = {Intra cavernous aneurysm of internal carotid artery masquerading as a pituitary adenoma: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {237}, pmid = {29636087}, issn = {1756-0500}, mesh = {Aged ; Carotid Artery, Internal/*diagnostic imaging ; Cerebral Angiography ; Female ; Humans ; Intracranial Aneurysm/*diagnostic imaging ; Pituitary Neoplasms/*diagnosis ; }, abstract = {BACKGROUND: Pituitary dysfunction in adults are often associated with tumors of the gland and manifests with mass effects and hypopituitarism. MRI of pituitary region often provides confirmation of the diagnosis and assists in planning neurosurgery.

CASE PRESENTATION: A 69 years old female evaluated for chronic headache was found to have a supra-sellar mass lesion that mimicked a pituitary tumor, with biochemical evidence of hypopituitarism. Cerebral angiogram confirmed the diagnosis of an aneurysm of the intracavernous internal carotid artery. She was successfully treated with coil embolization of the aneurysm and achieved resolution of symptoms and return of biochemistries to normal.

CONCLUSION: Carotid aneurysm can mimc pituitary tumours clinically and radiologically on MRI scan. This rare possibility should be considered in evaluating supra-sellar masses to avoid catastrophic consequences.}, } @article {pmid29636056, year = {2018}, author = {Gradilla, AC and Sanchez-Hernandez, D and Brunt, L and Scholpp, S}, title = {From top to bottom: Cell polarity in Hedgehog and Wnt trafficking.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {37}, pmid = {29636056}, issn = {1741-7007}, abstract = {Spatial organization of membrane domains within cells and cells within tissues is key to the development of organisms and the maintenance of adult tissue. Cell polarization is crucial for correct cell-cell signalling, which, in turn, promotes cell differentiation and tissue patterning. However, the mechanisms linking internal cell polarity to intercellular signalling are just beginning to be unravelled. The Hedgehog (Hh) and Wnt pathways are major directors of development and their malfunction can cause severe disorders like cancer. Here we discuss parallel advances into understanding the mechanism of Hedgehog and Wnt signal dissemination and reception. We hypothesize that cell polarization of the signal-sending and signal-receiving cells is crucial for proper signal spreading and activation of the pathway and, thus, fundamental for development of multicellular organisms.}, } @article {pmid29636028, year = {2018}, author = {Ioannidis, J and Donadeu, FX}, title = {Comprehensive analysis of blood cells and plasma identifies tissue-specific miRNAs as potential novel circulating biomarkers in cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {243}, pmid = {29636028}, issn = {1471-2164}, support = {BB/K501578/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biomarkers/blood ; Blood Cells/*metabolism ; Cattle/*blood/genetics ; Gene Expression Profiling ; MicroRNAs/*blood ; Organ Specificity ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: The potential of circulating miRNAs as biomarkers of tissue function, both in health and disease, has been extensively demonstrated in humans. In addition, circulating miRNA biomarkers offer significant potential towards improving the productivity of livestock species, however, such potential has been hampered by the absence of information on the nature and source of circulating miRNA populations in these species. In addition, many miRNAs originally proposed as robust biomarkers of a particular tissue or disease in humans have been later shown not to be tissue specific and thus to actually have limited biomarker utility. In this study, we comprehensively analysed miRNA profiles in plasma and cell fractions of blood from cattle with the aim to identify tissue-derived miRNAs which may be useful as biomarkers of tissue function in this important food animal species.

RESULTS: Using small RNA sequencing, we identified 92 miRNAs with significantly higher expression in plasma compared to paired blood cell samples (n = 4 cows). Differences in miRNA levels between plasma and cell fractions were validated for eight out of 10 miRNAs using RT-qPCR (n = 10 cows). Among miRNAs found to be enriched in plasma, we confirmed miR-122 (liver), miR-133a (muscle) and miR-215 (intestine) to be tissue-enriched, as reported for other species. Profiling of additional miRNAs across different tissues identified the human homologue, miR-802, as highly enriched specifically in liver.

CONCLUSIONS: These results provide novel information on the source of bovine circulating miRNAs and could significantly facilitate the identification of production-relevant tissue biomarkers in livestock. In particular, miR-802, a circulating miRNA not previously identified in cattle, can reportedly regulate insulin sensitivity and lipid metabolism, and thus could potentially provide a specific biomarker of liver function, a key parameter in the context of post-partum negative energy balance in dairy cows.}, } @article {pmid29636022, year = {2018}, author = {Piaskowski, J and Hardner, C and Cai, L and Zhao, Y and Iezzoni, A and Peace, C}, title = {Genomic heritability estimates in sweet cherry reveal non-additive genetic variance is relevant for industry-prioritized traits.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {23}, pmid = {29636022}, issn = {1471-2156}, support = {Hatch Project 1014919//National Institute of Food and Agriculture/ ; SCRI 2014-51181-22378//National Institute of Food and Agriculture/ ; }, abstract = {BACKGROUND: Sweet cherry is consumed widely across the world and provides substantial economic benefits in regions where it is grown. While cherry breeding has been conducted in the Pacific Northwest for over half a century, little is known about the genetic architecture of important traits. We used a genome-enabled mixed model to predict the genetic performance of 505 individuals for 32 phenological, disease response and fruit quality traits evaluated in the RosBREED sweet cherry crop data set. Genome-wide predictions were estimated using a repeated measures model for phenotypic data across 3 years, incorporating additive, dominance and epistatic variance components. Genomic relationship matrices were constructed with high-density SNP data and were used to estimate relatedness and account for incomplete replication across years.

RESULTS: High broad-sense heritabilities of 0.83, 0.77, and 0.76 were observed for days to maturity, firmness, and fruit weight, respectively. Epistatic variance exceeded 40% of the total genetic variance for maturing timing, firmness and powdery mildew response. Dominance variance was the largest for fruit weight and fruit size at 34% and 27%, respectively. Omission of non-additive sources of genetic variance from the genetic model resulted in inflation of narrow-sense heritability but minimally influenced prediction accuracy of genetic values in validation. Predicted genetic rankings of individuals from single-year models were inconsistent across years, likely due to incomplete sampling of the population genetic variance.

CONCLUSIONS: Predicted breeding values and genetic values revealed many high-performing individuals for use as parents and the most promising selections to advance for cultivar release consideration, respectively. This study highlights the importance of using the appropriate genetic model for calculating breeding values to avoid inflation of expected parental contribution to genetic gain. The genomic predictions obtained will enable breeders to efficiently leverage the genetic potential of North American sweet cherry germplasm by identifying high quality individuals more rapidly than with phenotypic data alone.}, } @article {pmid29636017, year = {2018}, author = {Wengier, DL and Lampard, GR and Bergmann, DC}, title = {Dissection of MAPK signaling specificity through protein engineering in a developmental context.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {60}, pmid = {29636017}, issn = {1471-2229}, support = {1R01GM086632//Foundation for the National Institutes of Health/International ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis Proteins/genetics/metabolism ; Gene Expression Regulation, Plant ; MAP Kinase Kinase 7/genetics/metabolism ; Mitogen-Activated Protein Kinase Kinases/genetics/metabolism ; Mitogen-Activated Protein Kinases/genetics/*metabolism ; Signal Transduction/genetics/physiology ; }, abstract = {BACKGROUND: Mitogen-activated protein kinases (MAPK) signaling affects many processes, some of which have different outcomes in the same cell. In Arabidopsis, activation of a MAPK cascade consisting of YODA, MKK4/5 and MPK3/6 inhibits early stages of stomatal developmental, but the ability to halt stomatal progression is lost at the later stage when guard mother cells (GMCs) transition to guard cells (GCs). Rather than downregulating cascade components, stomatal precursors must have a mechanism to prevent late stage inhibition because the same MKKs and MPKs mediate other physiological responses.

RESULTS: We artificially activated the MAPK cascade using MKK7, another MKK that can modulate stomatal development, and found that inhibition of stomatal development is still possible in GMCs. This suggests that MKK4/5, but not MKK7, are specifically prevented from inhibiting stomatal development. To identify regions of MKKs responsible for cell-type specific regulation, we used a domain swap approach with MKK7 and a battery of in vitro and in vivo kinase assays. We found that N-terminal regions of MKK5 and MKK7 establish specific signal-to-output connections like they do in other organisms, but they do so in combination with previously undescribed modules in the C-terminus. One of these modules encoding the GMC-specific regulation of MKK5, when swapped with sequences from the equivalent region of MKK7, allows MKK5 to mediate robust inhibition of late stomatal development.

CONCLUSIONS: Because MKK structure is conserved across species, the identification of new MKK specificity modules and signaling rules furthers our understanding of how eukaryotes create specificity in complex biological systems.}, } @article {pmid29636015, year = {2018}, author = {Lewandowska-Sabat, AM and Hansen, SF and Solberg, TR and Østerås, O and Heringstad, B and Boysen, P and Olsaker, I}, title = {MicroRNA expression profiles of bovine monocyte-derived macrophages infected in vitro with two strains of Streptococcus agalactiae.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {241}, pmid = {29636015}, issn = {1471-2164}, support = {233778//Norges Forskningsråd/ ; }, mesh = {Animals ; Cattle/*genetics/metabolism/*microbiology ; Female ; Gene Expression Regulation ; Macrophages/*metabolism/*microbiology ; MicroRNAs/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Streptococcus agalactiae/*physiology ; Transcriptome ; }, abstract = {BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that regulate gene expression at the post-transcriptional level and play a key role in the control of innate and adaptive immune responses. For a subclinical infection such as bovine streptococcal mastitis, early detection is a great challenge, and miRNA profiling could potentially assist in the diagnosis and contribute to the understanding of the pathogenicity and defense mechanisms. We have examined the miRNA repertoire and the transcript level of six key immune genes [tumor necrosis factor alpha (TNFα), interleukin-1 beta (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-10 (IL-10) and transforming growth factor beta 1 (TGFβ1)] during the early phase response of bovine immature macrophages to in vitro infection with live Streptococcus agalactiae. Next generation sequencing of small RNA libraries from 20 cultures of blood monocyte-derived macrophages exposed to either one of two sequence types of S. agalactiae (ST103 or ST12) for 6 h in vitro and unchallenged controls was performed.

RESULTS: Analyzes of over 356 million high quality sequence reads, revealed differential expression of 17 and 44 miRNAs (P < 0.05) in macrophages infected with ST103 and ST12, respectively, versus unchallenged control cultures. We also identified the expression of 31 potentially novel bovine miRNAs. Pathway analysis of the differentially regulated miRNAs and their predicted target genes in the macrophages infected with ST12 revealed significant enrichment for inflammatory response and apoptosis, while significant enrichment for integrin and GABA signaling were found in ST103 infected macrophages. Furthermore, both bacterial strains regulated miRNAs involved in the alternative activation of macrophages. The transcript levels of TNF-α, IL-1β, IL-6, IL-8 and IL-10 were significantly up-regulated by both bacterial strains, however the expression of TGFβ1 was significantly down-regulated only by ST12.

CONCLUSIONS: Our study identified pathogen-induced differential regulation of miRNAs controlling inflammation and polarization in bovine macrophages. This implies that miRNAs have potential to serve as biomarkers for early detection of bacterial infection.}, } @article {pmid29636014, year = {2018}, author = {Takahashi, Y and Sasaki, H and Okawara, S and Sasaki, N}, title = {Genetic loci for resistance to podocyte injury caused by the tensin2 gene deficiency in mice.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {24}, pmid = {29636014}, issn = {1471-2156}, support = {16K16606//Ministry of Education, Culture, Sports, Science and Technology/ ; 20302614//Ministry of Education, Culture, Sports, Science and Technology/ ; }, abstract = {BACKGROUND: Tensin2 is a focal adhesion-localized multidomain protein expressed in various tissues, and its dysfunction leads to alterations in podocytes. However, these podocyte-related manifestations are dependent on murine strain. Tensin2 dysfunction results in susceptible strains developing podocyte foot process effacement and massive albuminuria, whereas podocytes in resistant strains remain almost intact. In our previous studies, quantitative trait loci analysis and congenic analysis using resistant C57BL/6J and susceptible ICGN mice identified a modifier locus associated with podocyte injury caused by tensin2 dysfunction on chromosome 2. However, the effect of this modifier locus on chromosome 2 is insufficient to explain the resistance of C57BL/6J mice to tensin2 dysfunction, indicating the existence of other modifier genes.

RESULTS: Whereas previous studies focused on the severity of chronic kidney disease, the present study focused on podocyte injury. We performed a genome-wide linkage analysis of backcrosses between two tensin2-deficient mouse strains, B6.ICGN-Tns2 nph and FVB.ICGN-Tns2 nph , and detected a novel major modifier locus on chromosome 10. The combined effect of the C57BL/6J alleles of the two loci on chromosomes 2 and 10 reduced the urinary albumin excretion caused by tensin2 dysfunction to a level comparable to that of C57BL/6J mice.

CONCLUSIONS: These data indicate that the resistance to podocyte injury caused by tensin2 dysfunction is mainly produced by the effects of the modifier genes on the two loci. The identification of these modifier genes is expected to help elucidate the mechanism underlying podocyte injury.}, } @article {pmid29636009, year = {2018}, author = {Máté de Gérando, H and Wasels, F and Bisson, A and Clement, B and Bidard, F and Jourdier, E and López-Contreras, AM and Lopes Ferreira, N}, title = {Genome and transcriptome of the natural isopropanol producer Clostridium beijerinckii DSM6423.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {242}, pmid = {29636009}, issn = {1471-2164}, mesh = {2-Propanol/*metabolism ; Bioreactors/microbiology ; Clostridium beijerinckii/*genetics/metabolism/physiology ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Sequence Analysis, RNA ; Spores, Bacterial/genetics/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: There is a worldwide interest for sustainable and environmentally-friendly ways to produce fuels and chemicals from renewable resources. Among them, the production of acetone, butanol and ethanol (ABE) or Isopropanol, Butanol and Ethanol (IBE) by anaerobic fermentation has already a long industrial history. Isopropanol has recently received a specific interest and the best studied natural isopropanol producer is C. beijerinckii DSM 6423 (NRRL B-593). This strain metabolizes sugars into a mix of IBE with only low concentrations of ethanol produced (< 1 g/L). However, despite its relative ancient discovery, few genomic details have been described for this strain. Research efforts including omics and genetic engineering approaches are therefore needed to enable the use of C. beijerinckii as a microbial cell factory for production of isopropanol.

RESULTS: The complete genome sequence and a first transcriptome analysis of C. beijerinckii DSM 6423 are described in this manuscript. The combination of MiSeq and de novo PacBio sequencing revealed a 6.38 Mbp chromosome containing 6254 genomic objects. Three Mobile Genetic Elements (MGE) were also detected: a linear double stranded DNA bacteriophage (ϕ6423) and two plasmids (pNF1 and pNF2) highlighting the genomic complexity of this strain. A first RNA-seq transcriptomic study was then performed on 3 independent glucose fermentations. Clustering analysis allowed us to detect some key gene clusters involved in the main life cycle steps (acidogenesis, solvantogenesis and sporulation) and differentially regulated among the fermentation. These putative clusters included some putative metabolic operons comparable to those found in other reference strains such as C. beijerinckii NCIMB 8052 or C. acetobutylicum ATCC 824. Interestingly, only one gene was encoding for an alcohol dehydrogenase converting acetone into isopropanol, suggesting a single genomic event occurred on this strain to produce isopropanol.

CONCLUSIONS: We present the full genome sequence of Clostridium beijerinckii DSM 6423, providing a complete genetic background of this strain. This offer a great opportunity for the development of dedicated genetic tools currently lacking for this strain. Moreover, a first RNA-seq analysis allow us to better understand the global metabolism of this natural isopropanol producer, opening the door to future targeted engineering approaches.}, } @article {pmid29636007, year = {2018}, author = {Woods, LC and Li, Y and Ding, Y and Liu, J and Reading, BJ and Fuller, SA and Song, J}, title = {DNA methylation profiles correlated to striped bass sperm fertility.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {244}, pmid = {29636007}, issn = {1471-2164}, support = {Seed grant//USDA/NRAC/International ; Seed grant//USDA/NRAC/International ; }, mesh = {Animals ; Bass/*genetics/physiology ; *DNA Methylation ; Fertility/*genetics ; Gene Ontology ; Male ; Sequence Analysis, DNA ; Spermatozoa/*physiology ; }, abstract = {BACKGROUND: Striped bass (Morone saxatilis) spermatozoa are used to fertilize in vitro the eggs of white bass (M. chrysops) to produce the preferred hybrid for the striped bass aquaculture industry. Currently, only one source of domestic striped bass juveniles is available to growers that is not obtained from wild-caught parents and is thus devoid of any genetic improvement in phenotypic traits of importance to aquaculture. Sperm epigenetic modification has been predicted to be associated with fertility, which could switch genes on and off without changing the DNA sequence itself. DNA methylation is one of the most common epigenetic modification types and changes in sperm epigenetics can be correlated to sub-fertility or infertility in male striped bass. The objective of this study was to find the differentially methylated regions (DMRs) between high-fertility and sub-fertility male striped bass, which could potentially regulate the fertility performance.

RESULTS: In our present study, we performed DNA methylation analysis of high-fertility and sub-fertility striped bass spermatozoa through MBD-Seq methods. A total of 171 DMRs were discovered in striped bass sperm correlated to fertility. Based on the annotation of these DMRs, we conducted a functional classification analysis and two important groups of genes including the WDR3/UTP12 and GPCR families, were discovered to be related to fertility performance of striped bass. Proteins from the WDR3/UTP12 family are involved in forming the sperm flagella apparatus in vertebrates and GPCRs are involved in hormonal signaling and regulation of tissue development, proliferation and differentiation.

CONCLUSIONS: Our results contribute insights into understanding the mechanism of fertility in striped bass, which will provide powerful tools to maximize reproductive efficiencies and to identify those males with superior gametes for this important aquaculture species.}, } @article {pmid29636006, year = {2018}, author = {Tørresen, OK and Brieuc, MSO and Solbakken, MH and Sørhus, E and Nederbragt, AJ and Jakobsen, KS and Meier, S and Edvardsen, RB and Jentoft, S}, title = {Genomic architecture of haddock (Melanogrammus aeglefinus) shows expansions of innate immune genes and short tandem repeats.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {240}, pmid = {29636006}, issn = {1471-2164}, support = {#222378/F20//Norges Forskningsråd/ ; #234367/E40//Norges Forskningsråd/ ; }, mesh = {Animals ; Fish Proteins/*genetics ; Gadiformes/*genetics ; Genetic Variation ; *Genome ; Histocompatibility Antigens Class I/genetics ; Immunity, Innate/*genetics ; *Microsatellite Repeats ; NLR Proteins/genetics ; Population Density ; Toll-Like Receptors/genetics ; }, abstract = {BACKGROUND: Increased availability of genome assemblies for non-model organisms has resulted in invaluable biological and genomic insight into numerous vertebrates, including teleosts. Sequencing of the Atlantic cod (Gadus morhua) genome and the genomes of many of its relatives (Gadiformes) demonstrated a shared loss of the major histocompatibility complex (MHC) II genes 100 million years ago. An improved version of the Atlantic cod genome assembly shows an extreme density of tandem repeats compared to other vertebrate genome assemblies. Highly contiguous assemblies are therefore needed to further investigate the unusual immune system of the Gadiformes, and whether the high density of tandem repeats found in Atlantic cod is a shared trait in this group.

RESULTS: Here, we have sequenced and assembled the genome of haddock (Melanogrammus aeglefinus) - a relative of Atlantic cod - using a combination of PacBio and Illumina reads. Comparative analyses reveal that the haddock genome contains an even higher density of tandem repeats outside and within protein coding sequences than Atlantic cod. Further, both species show an elevated number of tandem repeats in genes mainly involved in signal transduction compared to other teleosts. A characterization of the immune gene repertoire demonstrates a substantial expansion of MCHI in Atlantic cod compared to haddock. In contrast, the Toll-like receptors show a similar pattern of gene losses and expansions. For the NOD-like receptors (NLRs), another gene family associated with the innate immune system, we find a large expansion common to all teleosts, with possible lineage-specific expansions in zebrafish, stickleback and the codfishes.

CONCLUSIONS: The generation of a highly contiguous genome assembly of haddock revealed that the high density of short tandem repeats as well as expanded immune gene families is not unique to Atlantic cod - but possibly a feature common to all, or most, codfishes. A shared expansion of NLR genes in teleosts suggests that the NLRs have a more substantial role in the innate immunity of teleosts than other vertebrates. Moreover, we find that high copy number genes combined with variable genome assembly qualities may impede complete characterization of these genes, i.e. the number of NLRs in different teleost species might be underestimates.}, } @article {pmid29636003, year = {2018}, author = {Nada Raja, T and Hu, TH and Zainudin, R and Lee, KS and Perkins, SL and Singh, B}, title = {Malaria parasites of long-tailed macaques in Sarawak, Malaysian Borneo: a novel species and demographic and evolutionary histories.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {49}, pmid = {29636003}, issn = {1471-2148}, support = {FRGS/ST03(05)/966/2013(07)//Ministry of Higher Education, Malaysia/International ; }, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Borneo ; Calibration ; DNA, Mitochondrial/genetics ; Demography ; Geography ; Humans ; Macaca fascicularis ; Malaria/*parasitology ; Malaysia ; Parasites/*genetics ; Phylogeny ; Plasmodium/classification ; Species Specificity ; Time Factors ; }, abstract = {BACKGROUND: Non-human primates have long been identified to harbour different species of Plasmodium. Long-tailed macaques (Macaca fascicularis), in particular, are reservoirs for P. knowlesi, P. inui, P. cynomolgi, P. coatneyi and P. fieldi. A previous study conducted in Sarawak, Malaysian Borneo, however revealed that long-tailed macaques could potentially harbour novel species of Plasmodium based on sequences of small subunit ribosomal RNA and circumsporozoite genes. To further validate this finding, the mitochondrial genome and the apicoplast caseinolytic protease M genes of Plasmodium spp. were sequenced from 43 long-tailed macaque blood samples.

RESULTS: Apart from several named species of malaria parasites, long-tailed macaques were found to be potentially infected with novel species of Plasmodium, namely one we refer to as "P. inui-like." This group of parasites bifurcated into two monophyletic clades indicating the presence of two distinct sub-populations. Further analyses, which relied on the assumption of strict co-phylogeny between hosts and parasites, estimated a population expansion event of between 150,000 to 250,000 years before present of one of these sub-populations that preceded that of the expansion of P. knowlesi. Furthermore, both sub-populations were found to have diverged from a common ancestor of P. inui approximately 1.5 million years ago. In addition, the phylogenetic analyses also demonstrated that long-tailed macaques are new hosts for P. simiovale.

CONCLUSIONS: Malaria infections of long-tailed macaques of Sarawak, Malaysian Borneo are complex and include a novel species of Plasmodium that is phylogenetically distinct from P. inui. These macaques are new natural hosts of P. simiovale, a species previously described only in toque monkeys (Macaca sinica) in Sri Lanka. The results suggest that ecological factors could affect the evolution of malaria parasites.}, } @article {pmid29636002, year = {2018}, author = {Hayashi, M and Crofts, N and Oitome, NF and Fujita, N}, title = {Analyses of starch biosynthetic protein complexes and starch properties from developing mutant rice seeds with minimal starch synthase activities.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {59}, pmid = {29636002}, issn = {1471-2229}, support = {25033AB, 28029C//The Program for the Promotion of Basic and Applied Research for Innovations in Bio-oriented Industry/ ; 19380007//The Ministry of Education, Sports, and Culture of Japan/ ; #15J40176//Grant-in-Aid for JSPS Fellows/ ; #16K18571//JSPS KAKENHI Grant-in-Aid for Young Scientists (B)/ ; }, mesh = {Amylopectin/metabolism ; Amylose/metabolism ; Oryza/*enzymology/*metabolism ; Seeds/*enzymology/*metabolism ; Starch/*metabolism ; Starch Synthase/*metabolism ; }, abstract = {BACKGROUND: Starch is the major component of cereal grains and is composed of essentially linear amylose and highly branched amylopectin. The properties and composition of starch determine the use and value of grains and their products. Starch synthase (SS) I, SSIIa, and SSIIIa play central roles in amylopectin biosynthesis. These three SS isozymes also affect seed development, as complete loss of both SSI and SSIIIa under reduced SSIIa activity in rice lead to sterility, whereas presence of minimal SSI or SSIIIa activity is sufficient for generating fertile seeds. SSs, branching enzymes, and/or debranching enzymes form protein complexes in cereal. However, the relationship between starch properties and the formation of protein complexes remain largely unknown. To better understand this phenomenon, properties of starch and protein complex formation were analyzed using developing mutant rice seeds (ss1 L /ss2a L /ss3a) in which all three major SS activities were reduced.

RESULTS: The SS activity of ss1 L /ss2a L /ss3a was 25%-30% that of the wild-type. However, the grain weight of ss1 L /ss2a L /ss3a was 89% of the wild-type, 55% of which was starch, showing considerable starch synthesis. The reduction of soluble SS activity in ss1 L /ss2a L /ss3a resulted in increased levels of ADP-glucose pyrophosphorylase and granule-bound starch synthase I, which are responsible for substrate synthesis and amylose synthesis, respectively. Together, these features led to an increase in apparent amylose content (34%) in ss1 L /ss2a L /ss3a compared with wild-type (20%). Gel filtration chromatography of the soluble proteins in ss1 L /ss2a L /ss3a showed that the majority of the starch biosynthetic enzymes maintained the similar elution patterns as wild-type, except that the amounts of high-molecular-weight SSI (> 300 kDa) were reduced and SSIIa of approximately 200-300 kDa were present instead of those > 440 kDa, which predominate in wild-type. Immuno-precipitation analyses suggested that the interaction between the starch biosynthetic enzymes maybe reduced or weaker than in wild-type.

CONCLUSIONS: Although major SS isozymes were simultaneously reduced in ss1 L /ss2a L /ss3a rice, active protein complexes were formed with a slightly altered pattern, suggesting that the assembly of protein complexes may be complemented among the SS isozymes. In addition, ss1 L /ss2a L /ss3a maintained the ability to synthesize starch and accumulated less amylopectin and more amylose in starch.}, } @article {pmid29636001, year = {2018}, author = {Martin, RC and Vining, K and Dombrowski, JE}, title = {Genome-wide (ChIP-seq) identification of target genes regulated by BdbZIP10 during paraquat-induced oxidative stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {58}, pmid = {29636001}, issn = {1471-2229}, mesh = {Basic-Leucine Zipper Transcription Factors/*metabolism ; Brachypodium/metabolism ; Chromatin Immunoprecipitation ; Gene Expression Regulation, Plant/drug effects ; Oxidative Stress/drug effects ; Paraquat/*pharmacology ; }, abstract = {BACKGROUND: bZIP transcription factors play a significant role in many aspects of plant growth and development and also play critical regulatory roles during plant responses to various stresses. Overexpression of the Brachypodium bZIP10 (Bradi1g30140) transcription factor conferred enhanced oxidative stress tolerance and increased viability when plants or cells were exposed to the herbicide paraquat. To gain a better understanding of genes involved in bZIP10 conferred oxidative stress tolerance, chromatin immunoprecipitation followed by high throughput sequencing (ChIP-Seq) was performed on BdbZIP10 overexpressing plants in the presence of oxidative stress.

RESULTS: We identified a transcription factor binding motif, TGDCGACA, different from most known bZIP TF motifs but with strong homology to the Arabidopsis zinc deficiency response element. Analysis of the immunoprecipitated sequences revealed an enrichment of gene ontology groups with metal ion transmembrane transporter, transferase, catalytic and binding activities. Functional categories including kinases and phosphotransferases, cation/ion transmembrane transporters, transferases (phosphorus-containing and glycosyl groups), and some nucleoside/nucleotide binding activities were also enriched.

CONCLUSIONS: Brachypodium bZIP10 is involved in zinc homeostasis, as it relates to oxidative stress.}, } @article {pmid29636000, year = {2018}, author = {Lv, X and Cheng, J and Meng, Y and Chang, Y and Xia, L and Wen, Z and Ge, D and Liu, S and Yang, Q}, title = {Disjunct distribution and distinct intraspecific diversification of Eothenomys melanogaster in South China.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {50}, pmid = {29636000}, issn = {1471-2148}, support = {31372177//National Natural Science Foundation of China/International ; NA150142//Newton Fund (GB)/International ; Y229YX5105//Key Laboratory of Zoological Systematics and Evolution of the Chinese Academy of Sciences/International ; }, mesh = {Animals ; Arvicolinae/genetics/*physiology ; Bayes Theorem ; *Biodiversity ; Cell Nucleus/genetics ; China ; DNA, Mitochondrial/genetics ; Demography ; Genetic Variation ; Geography ; Islands ; Phylogeny ; Phylogeography ; Species Specificity ; Taiwan ; Time Factors ; }, abstract = {BACKGROUND: South China encompasses complex and diverse landforms, giving rise to high biological diversity and endemism from the Hengduan Mountains to Taiwan Island. Many species are widely distributed across South China with similar disjunct distribution patterns. To explore the causes of these disjunct distribution patterns and their genetic consequences, we investigated the endemic species Père David's Chinese Vole (Eothenomys melanogaster) by integrating geological and ecological factors. We analysed the genetic structure and divergence time of E. melanogaster based on fast-evolving mitochondrial and nuclear markers using Bayesian trees and coalescent species tree approaches. Historical scenarios of distribution range and demography were reconstructed based on spatial interpolations of genetic diversity and distance, extended Bayesian skyline plots, phylogeographic diffusion analysis, and ecological niche modelling (ENM) during different periods. We also assessed the relationships between geographical distance/ecological vicariance and genetic distance (isolation by distance, IBD; isolation by environment, IBE).

RESULTS: The genetic analysis revealed three deeply divergent clades-Southeast, Southwest and Central clades, centred on the Wuyi Mountains, the Yunnan-Guizhou Plateau (YGP) and the mountains around the Sichuan Basin, respectively-that have mostly developed since the Pleistocene. IBD played an important role in early divergence, and geological events (sedimentation of plains and linking of palaeo-rivers) and IBE further reinforced genetic differentiation. ENM shows the importance of suitable habitats and elevations.

CONCLUSIONS: Our results suggest that the primary cause of the disjunct distribution in E. melanogaster is the high dependence on middle-high-altitude habitat in the current period. Mountains in the occurence range have served as "sky islands" for E. melanogaster and hindered gene flow. Pleistocene climatic cycles facilitated genetic admixture in cold periods and genetic diversification in warm periods for inland clades. During cold periods, these cycles led to multiple colonization events between the mainland and Taiwan and erased genetic differentiation.}, } @article {pmid29635458, year = {2018}, author = {Nye, J and Laayouni, H and Kuhlwilm, M and Mondal, M and Marques-Bonet, T and Bertranpetit, J}, title = {Selection in the Introgressed Regions of the Chimpanzee Genome.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1132-1138}, pmid = {29635458}, issn = {1759-6653}, support = {U01 MH106874/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Female ; *Genetics, Population ; Genome/*genetics ; Genomics ; Haplotypes/genetics ; Humans ; Male ; Pan paniscus/genetics ; Pan troglodytes/*genetics ; Selection, Genetic/*genetics ; }, abstract = {During the demographic history of the Pan clade, there has been gene-flow between species, likely >200,000 years ago. Bonobo haplotypes in three subspecies of chimpanzee have been identified to be segregating in modern-day chimpanzee populations, suggesting that these haplotypes, with increased differentiation, may be a target of natural selection. Here, we investigate signatures of adaptive introgression within the bonobo-like haplotypes in chimpanzees using site frequency spectrum-based tests. We find evidence for subspecies-specific adaptations in introgressed regions involved with male reproduction in central chimpanzees, the immune system in eastern chimpanzees, female reproduction and the nervous system in Nigeria-Cameroon chimpanzees. Furthermore, our results indicate signatures of balancing selection in some of the putatively introgressed regions. This might be the product of long-term balancing selection resulting in a similar genomic signature as introgression, or possibly balancing selection acting on alleles reintroduced through gene flow.}, } @article {pmid29635439, year = {2018}, author = {Lim, ML and Brooks, MD and Boothe, MA and Krzmarzick, MJ}, title = {Novel bacterial diversity is enriched with chloroperoxidase-reacted organic matter under anaerobic conditions.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy050}, pmid = {29635439}, issn = {1574-6941}, abstract = {Fungal chloroperoxidases (CPOs) are one class of enzymes that produce natural organochlorides in soils. The microbial degradation of these organochlorides is not well known, though has implications for bioremediation, microbial ecology and natural chlorine and carbon cycling. In this study, Illumina-based 16S rRNA gene sequencing and real-time quantitative PCR (qPCR) was used to characterize the bacterial community enriched from an amendment of organic matter reacted with CPO under conditions conducive towards chlorination (CPO-OM). In total, 17 bacterial groups were enriched in triplicate microcosms inoculated with creek sediment and amended with CPO-OM. These bacterial groups were neither enriched with amendments of non-reacted organic matter extract, with or without oxidative stress induced by H2O2, nor with amendments of organic matter reacted with CPO under non-chlorinating conditions. Of these, only two represented genera with known organohalide respiring bacteria-Dehalogenimonas and Dehalobacter. The genus Acetobacterium was also found to be enriched but the other 14 groups of enriched bacteria do not currently have any close phylogenetically related isolates. This study highlights a gap in the current understanding of the microbiology involved in natural organochloride turnover and suggests that CPO-OM could be used for isolating and culturing strains from novel bacteria genera.}, } @article {pmid29635416, year = {2018}, author = {Barton, HJ and Zeng, K}, title = {New Methods for Inferring the Distribution of Fitness Effects for INDELs and SNPs.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1536-1546}, pmid = {29635416}, issn = {1537-1719}, abstract = {Small insertions and deletions (INDELs; ≤50 bp) are the most common type of variability after single nucleotide polymorphism (SNP). However, compared with SNPs, we know little about the distribution of fitness effects (DFE) of new INDEL mutations and how prevalent adaptive INDEL substitutions are. Studying INDELs has been difficult partly because identifying ancestral states at these sites is error-prone and misidentification can lead to severely biased estimates of the strength of selection. To solve these problems, we develop new maximum likelihood methods, which use polymorphism data to simultaneously estimate the DFE, the mutation rate, and the misidentification rate. These methods are applicable to both INDELs and SNPs. Simulations show that they can provide highly accurate results. We applied the methods to an INDEL polymorphism data set in Drosophila melanogaster. We found that the DFE for polymorphic INDELs in protein-coding regions is bimodal, with the variants being either nearly neutral or strongly deleterious. Based on the DFE, we estimated that 71.5-83.7% of the INDEL substitutions that took place along the D. melanogaster lineage were fixed by positive selection, which is comparable with the prevalence of adaptive substitutions at nonsynonymous sites. The new methods have been implemented in the software package anavar.}, } @article {pmid29635372, year = {2018}, author = {Kwong, WK and Steele, MI and Moran, NA}, title = {Genome Sequences of Apibacter spp., Gut Symbionts of Asian Honey Bees.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1174-1179}, pmid = {29635372}, issn = {1759-6653}, support = {R01 GM108477/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bees/genetics/*microbiology ; Flavobacteriaceae/*genetics ; Gastrointestinal Tract/microbiology ; Host Specificity/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Whole Genome Sequencing ; }, abstract = {Honey bees have distinct gut microbiomes consisting almost entirely of several host-specific bacterial species. We present the genomes of three strains of Apibacter spp., bacteria of the Bacteroidetes phylum that are endemic to Asian honey bee species (Apis dorsata and Apis cerana). The Apibacter strains have similar metabolic abilities to each other and to Apibacter mensalis, a species isolated from a bumble bee. They use microaerobic respiration and fermentation to catabolize a limited set of monosaccharides and dicarboxylic acids. All strains are capable of gliding motility and encode a type IX secretion system. Two strains and A. mensalis have type VI secretion systems, and all strains encode Rhs or VgrG proteins used in intercellular interactions. The characteristics of Apibacter spp. are consistent with adaptions to life in a gut environment; however, the factors responsible for host-specificity and mutualistic interactions remain to be uncovered.}, } @article {pmid29635365, year = {2018}, author = {Holm, KO and Bækkedal, C and Söderberg, JJ and Haugen, P}, title = {Complete Genome Sequences of Seven Vibrio anguillarum Strains as Derived from PacBio Sequencing.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1127-1131}, pmid = {29635365}, issn = {1759-6653}, mesh = {DNA Transposable Elements/*genetics ; Genome, Bacterial/genetics ; High-Throughput Nucleotide Sequencing ; Molecular Sequence Annotation ; Sequence Analysis, DNA ; Vibrio/*genetics ; *Whole Genome Sequencing ; }, abstract = {We report here the complete genome sequences of seven Vibrio anguillarum strains isolated from multiple geographic locations, thus increasing the total number of genomes of finished quality to 11. The genomes were de novo assembled from long-sequence PacBio reads. Including draft genomes, a total of 44 V. anguillarum genomes are currently available in the genome databases. They represent an important resource in the study of, for example, genetic variations and for identifying virulence determinants. In this article, we present the genomes and basic genome comparisons of the 11 complete genomes, including a BRIG analysis, and pan genome calculation. We also describe some structural features of superintegrons on chromosome 2 s, and associated insertion sequence (IS) elements, including 18 new ISs (ISVa3 - ISVa20), both of importance in the complement of V. anguillarum genomes.}, } @article {pmid29635333, year = {2018}, author = {Valente, C and Alvarez, L and Marques, PI and Gusmão, L and Amorim, A and Seixas, S and João Prata, M}, title = {Genes from the TAS1R and TAS2R Families of Taste Receptors: Looking for Signatures of Their Adaptive Role in Human Evolution.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1139-1152}, pmid = {29635333}, issn = {1759-6653}, mesh = {Africa ; Alleles ; Evolution, Molecular ; Genetic Variation/genetics ; Haplotypes/genetics ; Humans ; Polymorphism, Single Nucleotide/genetics ; Receptors, G-Protein-Coupled/*genetics ; Taste/*genetics ; Taste Buds ; }, abstract = {Taste perception is crucial in monitoring food intake and, hence, is thought to play a significant role in human evolution. To gain insights into possible adaptive signatures in genes encoding bitter, sweet, and umami taste receptors, we surveyed the available sequence variation data from the 1000 Genomes Project Phase 3 for TAS1R (TAS1R1-3) and TAS2R (TAS2R16 and TAS2R38) families. Our study demonstrated that genes from these two families have experienced contrasting evolutionary histories: While TAS1R1 and TAS1R3 showed worldwide evidence of positive selection, probably correlated with improved umami and sweet perception, the patterns of variation displayed by TAS2R16 and TAS2R38 were more consistent with scenarios of balancing selection that possibly conferred a heterozygous advantage associated with better capacity to perceive a wide range of bitter compounds. In TAS2R16, such adaptive events appear to have occurred restrictively in mainland Africa, whereas the strongest evidence in TAS2R38 was detected in Europe. Despite plausible associations between taste perception and the TAS1R and TAS2R selective signatures, we cannot discount other biological mechanisms as driving the evolutionary trajectories of those TAS1R and TAS2R members, especially given recent findings of taste receptors behaving as the products of pleiotropic genes involved in many functions outside the gustatory system.}, } @article {pmid29635329, year = {2018}, author = {Cremen, MCM and Leliaert, F and Marcelino, VR and Verbruggen, H}, title = {Large Diversity of Nonstandard Genes and Dynamic Evolution of Chloroplast Genomes in Siphonous Green Algae (Bryopsidales, Chlorophyta).}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1048-1061}, pmid = {29635329}, issn = {1759-6653}, mesh = {Chlorophyta/*genetics ; *Evolution, Molecular ; Genetic Variation ; Genome, Chloroplast/*genetics ; Genomics ; Phylogeny ; Repetitive Sequences, Nucleic Acid/*genetics ; }, abstract = {Chloroplast genomes have undergone tremendous alterations through the evolutionary history of the green algae (Chloroplastida). This study focuses on the evolution of chloroplast genomes in the siphonous green algae (order Bryopsidales). We present five new chloroplast genomes, which along with existing sequences, yield a data set representing all but one families of the order. Using comparative phylogenetic methods, we investigated the evolutionary dynamics of genomic features in the order. Our results show extensive variation in chloroplast genome architecture and intron content. Variation in genome size is accounted for by the amount of intergenic space and freestanding open reading frames that do not show significant homology to standard plastid genes. We show the diversity of these nonstandard genes based on their conserved protein domains, which are often associated with mobile functions (reverse transcriptase/intron maturase, integrases, phage- or plasmid-DNA primases, transposases, integrases, ligases). Investigation of the introns showed proliferation of group II introns in the early evolution of the order and their subsequent loss in the core Halimedineae, possibly through RT-mediated intron loss.}, } @article {pmid29635328, year = {2018}, author = {Wilson Sayres, MA}, title = {Genetic Diversity on the Sex Chromosomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1064-1078}, pmid = {29635328}, issn = {1759-6653}, support = {R35 GM124827/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chromosomes, Human, X/genetics ; Chromosomes, Human, Y/genetics ; Female ; Genes, sry/genetics ; *Genetic Variation ; Humans ; Male ; Recombination, Genetic/genetics ; Selection, Genetic/*genetics ; Sex Chromosomes/*genetics ; Sex Determination Processes/*genetics ; }, abstract = {Levels and patterns of genetic diversity can provide insights into a population's history. In species with sex chromosomes, differences between genomic regions with unique inheritance patterns can be used to distinguish between different sets of possible demographic and selective events. This review introduces the differences in population history for sex chromosomes and autosomes, provides the expectations for genetic diversity across the genome under different evolutionary scenarios, and gives an introductory description for how deviations in these expectations are calculated and can be interpreted. Predominantly, diversity on the sex chromosomes has been used to explore and address three research areas: 1) Mating patterns and sex-biased variance in reproductive success, 2) signatures of selection, and 3) evidence for modes of speciation and introgression. After introducing the theory, this review catalogs recent studies of genetic diversity on the sex chromosomes across species within the major research areas that sex chromosomes are typically applied to, arguing that there are broad similarities not only between male-heterogametic (XX/XY) and female-heterogametic (ZZ/ZW) sex determination systems but also any mating system with reduced recombination in a sex-determining region. Further, general patterns of reduced diversity in nonrecombining regions are shared across plants and animals. There are unique patterns across populations with vastly different patterns of mating and speciation, but these do not tend to cluster by taxa or sex determination system.}, } @article {pmid29635246, year = {2018}, author = {Sakai, ST and Whitt, B and Arsznov, BM and Lundrigan, BL}, title = {Endocranial Development in the Coyote (Canis latrans) and Gray Wolf (Canis lupus): A Computed Tomographic Study.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {2}, pages = {65-81}, doi = {10.1159/000487427}, pmid = {29635246}, issn = {1421-9743}, abstract = {The purpose of this study was to examine the pattern of postnatal brain growth in two wild canid species: the coyote (Canis latrans) and gray wolf (Canis lupus). Adult regional and total brain volume differences were also compared between the two species as well as within each species by sex. Three-dimensional virtual endocasts of endocranial airspace were created from computed tomography scans of 52 coyote skulls (28 female, 24 male; 1 day to 13.4 years) and 46 gray wolf skulls (25 female, 21 male; 1 day to 7.9 years). Age was known in coyotes or estimated from dentition patterns in wolves. The 95% asymptotic growth of the endocranium is completed by 21 weeks in male and 17.5 weeks in female coyotes and by 27 weeks in male and 18.5 weeks in female wolves. These ages are well before age at first reproduction (coyote - 40.4 weeks; wolf - 91.25 weeks). Skull growth as measured by centroid size lags behind endocranial growth but is also completed before sexual maturity. Intra- and interspecific comparisons of brain volumes in the adult wolves and coyotes revealed that relative anterior cerebrum (AC) volume was greater in males than females in both species. Relative brain size was greater in the coyote than in the wolf as was relative cerebrum volume. However, relative AC volume and relative cerebellum and brainstem volume was greater in the wolf than coyote. One explanation for the increased AC volume in males compared to females may be related to the role of social information processing. However, additional data are needed to determine the correspondence between regional volumes and functional differences either between or within these species. Nonetheless, these findings provide important baseline data for further studies on wild canid brain variations and development.}, } @article {pmid29635025, year = {2018}, author = {Kallal, RJ and Fernández, R and Giribet, G and Hormiga, G}, title = {A phylotranscriptomic backbone of the orb-weaving spider family Araneidae (Arachnida, Araneae) supported by multiple methodological approaches.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {129-140}, doi = {10.1016/j.ympev.2018.04.007}, pmid = {29635025}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Genome ; *Phylogeny ; Spiders/*genetics ; Transcriptome/*genetics ; }, abstract = {The orb-weaving spider family Araneidae is extremely diverse (>3100 spp.) and its members can be charismatic terrestrial arthropods, many of them recognizable by their iconic orbicular snare web, such as the common garden spiders. Despite considerable effort to better understand their backbone relationships based on multiple sources of data (morphological, behavioral and molecular), pervasive low support remains in recent studies. In addition, no overarching phylogeny of araneids is available to date, hampering further comparative work. In this study, we analyze the transcriptomes of 33 taxa, including 19 araneids - 12 of them new to this study - representing most of the core family lineages, to examine the relationships within the family using genomic-scale datasets resulting from various methodological treatments, namely ortholog selection and gene occupancy as a measure of matrix completion. Six matrices were constructed to assess these effects by varying orthology inference method and gene occupancy threshold. Orthology methods used are the benchmarking tool BUSCO and the tree-based method UPhO; three gene occupancy thresholds (45%, 65%, 85%) were used to assess the effect of missing data. Gene tree and species tree-based methods (including multi-species coalescent and concatenation approaches, as well as maximum likelihood and Bayesian inference) were used totalling 17 analytical treatments. The monophyly of Araneidae and the placement of core araneid lineages were supported, together with some previously unsound backbone divergences; these include high support for Zygiellinae as the earliest diverging subfamily (followed by Nephilinae), the placement of Gasteracanthinae as sister group to Cyclosa and close relatives, and close relationships between the Araneus + Neoscona clade and Cyrtophorinae + Argiopinae clade. Incongruences were relegated to short branches in the clade comprising Cyclosa and its close relatives. We found congruence between most of the completed analyses, with minimal topological effects from occupancy/missing data and orthology assessment. The resulting number of genes by certain combinations of orthology and occupancy thresholds being analyzed had the greatest effect on the resulting trees, with anomalous outcomes recovered from analysis of lower numbers of genes.}, } @article {pmid29635024, year = {2018}, author = {Cheng, DQ and Piel, WH}, title = {The origins of the Psechridae: Web-building lycosoid spiders.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {213-219}, doi = {10.1016/j.ympev.2018.03.035}, pmid = {29635024}, issn = {1095-9513}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; Female ; Genome ; Likelihood Functions ; Phylogeny ; Silk/*biosynthesis ; Spiders/*classification ; Transcriptome/genetics ; }, abstract = {Psechrids are an enigmatic family of S.E. Asian spiders. This small family builds sheet webs and even orb webs, yet unlike other orb weavers, its putative relatives are largely cursorial lycosoids - a superfamily of approximately seven spider families related to wolf spiders. The orb web was invented at least twice: first in a very ancient event, and then second, within this clade of wolf-like spiders that reinvented this ability. Exactly how the spiders modified their silks, anatomy, and behaviors to accomplish this transition requires that we identify their precise evolutionary origins - yet, thus far, molecular phylogenies show poor support and considerable disagreement. Using phylogenomic methods based on whole body transcriptomes for psechrids and their putative relatives, we have recovered a well-supported phylogeny that places the Psechridae sister to the Ctenidae - a family of mostly cursorial habits but that, as with all psechrids, retains some cribellate species. Although this position reinforces the prevailing view that orb weaving in psechrids is largely a consequence of convergence, it is still possible that some components of this behavior are retained or resurrected in common with more distant true orb weaving ancestors.}, } @article {pmid29634916, year = {2018}, author = {Hinaux, H and Bachem, K and Battistara, M and Rossi, M and Xin, Y and Jaenichen, R and Le Poul, Y and Arnoult, L and Kobler, JM and Grunwald Kadow, IC and Rodermund, L and Prud'homme, B and Gompel, N}, title = {Revisiting the developmental and cellular role of the pigmentation gene yellow in Drosophila using a tagged allele.}, journal = {Developmental biology}, volume = {438}, number = {2}, pages = {111-123}, doi = {10.1016/j.ydbio.2018.04.003}, pmid = {29634916}, issn = {1095-564X}, mesh = {Alleles ; Animals ; Cell Tracking/methods ; Drosophila/genetics ; Drosophila Proteins/genetics/*metabolism/*physiology ; Fluorescent Antibody Technique/methods ; Gene Expression Regulation, Developmental/genetics ; Gene Frequency/genetics ; Larva/metabolism ; Melanins/genetics ; Phenotype ; Pigmentation/genetics/physiology ; Pupa/metabolism ; }, abstract = {Pigmentation is a diverse and ecologically relevant trait in insects. Pigment formation has been studied extensively at the genetic and biochemical levels. The temporality of pigment formation during animal development, however, is more elusive. Here, we examine this temporality, focusing on yellow, a gene involved in the formation of black melanin. We generated a protein-tagged yellow allele in the fruit fly Drosophila melanogaster, which allowed us to precisely describe Yellow expression pattern at the tissue and cellular levels throughout development. We found Yellow expressed in the pupal epidermis in patterns prefiguring black pigmentation. We also found Yellow expressed in a few central neurons from the second larval instar to adult stages, including a subset of neurons adjacent to the clock neurons marked by the gene Pdf. We then specifically examined the dynamics of Yellow expression domain and subcellular localization in relationship to pigment formation. In particular, we showed how a late step of re-internalization is regulated by the large low-density lipoprotein receptor-related protein Megalin. Finally we suggest a new function for Yellow in the establishment of sharp pigmentation pattern boundaries, whereby this protein may assume a structural role, anchoring pigment deposits or pigmentation enzymes in the cuticle.}, } @article {pmid29633558, year = {2018}, author = {Wagner, GP}, title = {The evolution of empathy and devo-evo-What is the connection?.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {2}, pages = {65}, doi = {10.1002/jez.b.22801}, pmid = {29633558}, issn = {1552-5015}, mesh = {*Biological Evolution ; Coitus/physiology ; Developmental Biology ; Empathy/*genetics/*physiology ; Female ; Humans ; Male ; Orgasm/physiology ; Selection, Genetic ; }, } @article {pmid29633524, year = {2018}, author = {Kopycińska, M and Lipa, P and Cieśla, J and Kozieł, M and Janczarek, M}, title = {Extracellular polysaccharide protects Rhizobium leguminosarum cells against zinc stress in vitro and during symbiosis with clover.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {355-368}, doi = {10.1111/1758-2229.12646}, pmid = {29633524}, issn = {1758-2229}, abstract = {Rhizobium leguminosarum bv. trifolii is a soil bacterium that establishes symbiosis with clover (Trifolium spp.) under nitrogen-limited conditions. This microorganism produces exopolysaccharide (EPS), which plays an important role in symbiotic interactions with the host plant. The aim of the current study was to establish the role of EPS in the response of R. leguminosarum bv. trifolii cells, free-living and during symbiosis, to zinc stress. We show that EPS-deficient mutants were more sensitive to Zn2+ exposure than EPS-producing strains, and that EPS overexpression conferred some protection onto the strains beyond that observed in the wild type. Exposure of the bacteria to Zn2+ ions stimulated EPS and biofilm production, and increased cell hydrophobicity. However, zinc stress negatively affected the motility and attachment of bacteria to clover roots, as well as the symbiosis with the host plant. In the presence of Zn2+ ions, cell viability, root attachment, biofilm formation and symbiotic efficiency of EPS-overproducing strains were significantly higher than those of the EPS-deficient mutants. We conclude that EPS plays an important role in the adaptation of rhizobia to zinc stress, in both the free-living stage and during symbiosis.}, } @article {pmid29633519, year = {2018}, author = {Hesse, C and Schulz, F and Bull, CT and Shaffer, BT and Yan, Q and Shapiro, N and Hassan, KA and Varghese, N and Elbourne, LDH and Paulsen, IT and Kyrpides, N and Woyke, T and Loper, JE}, title = {Genome-based evolutionary history of Pseudomonas spp.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14130}, pmid = {29633519}, issn = {1462-2920}, abstract = {Pseudomonas is a large and diverse genus of Gammaproteobacteria. To provide a framework for discovery of evolutionary and taxonomic relationships of these bacteria, we compared the genomes of type strains of 163 species and 3 additional subspecies of Pseudomonas, including 118 genomes sequenced herein. A maximum likelihood phylogeny of the 166 type strains based on protein sequences of 100 single-copy orthologous genes revealed thirteen groups of Pseudomonas, composed of two to sixty three species each. Pairwise average nucleotide identities and alignment fractions were calculated for the data set of the 166 type strains and 1224 genomes of Pseudomonas available in public databases. Results revealed that 394 of the 1224 genomes were distinct from any type strain, suggesting that the type strains represent only a fraction of the genomic diversity of the genus. The core genome of Pseudomonas was determined to contain 794 genes conferring primarily housekeeping functions. The results of this study provide a phylogenetic framework for future studies aiming to resolve the classification and phylogenetic relationships, identify new gene functions and phenotypes, and explore the ecological and metabolic potential of the Pseudomonas spp.}, } @article {pmid29633455, year = {2018}, author = {Zheng, Y and He, L and Asiamah, TK and Otto, M}, title = {Colonization of medical devices by staphylococci.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3141-3153}, pmid = {29633455}, issn = {1462-2920}, support = {Z01 AI000904-07/NULL/Intramural NIH HHS/United States ; ZIA AI001080//Division of Intramural Research, National Institute of Allergy and Infectious Diseases/ ; }, abstract = {The use of medical devices in modern medicine is constantly increasing. Despite the multiple precautionary strategies that are being employed in hospitals, which include increased hygiene and sterilization measures, bacterial infections on these devices still happen frequently. Staphylococci are among the major causes of medical device infection. This is mostly due to the strong capacity of those bacteria to form device-associated biofilms, which provide resistance to chemical and physical treatments as well as attacks by the host's immune system. Biofilm development is a multistep process with specific factors participating in each step. It is tightly regulated to provide a balance between biofilm expansion and detachment. Detachment from a biofilm on a medical device can lead to severe systemic infection, such as bacteremia and sepsis. While our understanding of staphylococcal biofilm formation has increased significantly and staphylococcal biofilm formation on medical devices is among the best understood biofilm-associated infections, the extensive effort put in preclinical studies with the goal to find novel therapies against staphylococcal device-associated infections has not yet resulted in efficient, applicable therapeutic options for that difficult-to-treat type of disease.}, } @article {pmid29632975, year = {2018}, author = {Wang, R and Chen, C and Su, Y and Yu, X and Zhang, C and Fu, G and Han, S and Pan, X and Qiu, J and Li, X and Wu, M}, title = {Agromyces mangrovi sp. nov., a Novel Actinobacterium Isolated from Mangrove Soil.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1055-1061}, pmid = {29632975}, issn = {1432-0991}, support = {31470005//National Natural Science Foundation of China/ ; }, mesh = {*Actinobacteria/classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Base Sequence ; China ; DNA, Bacterial/genetics ; Fatty Acids/analysis ; Nucleic Acid Hybridization ; Peptidoglycan/analysis ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Wetlands ; }, abstract = {A novel, Gram-stain-positive, microaerophilic to aerobic, non-endospore-forming, no-motile and rod-shaped bacterium designated Q14T was isolated from mangrove soil samples collected on chengmai, Hainan province, China. Strain Q14T was able to grow at 10-40 °C (optimum 30 °C), pH 5.5-10.0 (optimum 6.5-8.0) and with 0.5-6% (w/v) NaCl (optimum 1%). The genomic DNA G+C content was 70.1%. The chemotaxonomic analysis showed that the predominant isoprenoid quinone was MK-12 and the major fatty acids were anteiso-C15:0, iso-C17:0 and anteiso-C17:0. The major polar lipids of strain Q14T were diphosphatidylglycerol, phosphatidylglycerol and one glycolipid. The strain Q14T contained 2,4-diaminobutylic acid (A2bu), alanine acid, glutamic acid and glycine in the peptidoglycans. The phylogenetic analysis and DNA-DNA hybridization, along with the phenotypic and chemotaxonomic characteristics, indicate that strain Q14T as a novel species of the genus Agromyces, for which the name Agromyces mangrovi sp. nov. is proposed. The type strain is Q14T (= MCCC 1K03191T = KCTC 39814T).}, } @article {pmid29632553, year = {2018}, author = {Piotrowska, MJ and Riddell, C and Hoebe, PN and Ennos, RA}, title = {Planting exotic relatives has increased the threat posed by Dothistroma septosporum to the Caledonian pine populations of Scotland.}, journal = {Evolutionary applications}, volume = {11}, number = {3}, pages = {350-363}, pmid = {29632553}, issn = {1752-4571}, abstract = {To manage emerging forest diseases and prevent their occurrence in the future, it is essential to determine the origin(s) of the pathogens involved and identify the management practices that have ultimately caused disease problems. One such practice is the widespread planting of exotic tree species within the range of related native taxa. This can lead to emerging forest disease both by facilitating introduction of exotic pathogens and by providing susceptible hosts on which epidemics of native pathogens can develop. We used microsatellite markers to determine the origins of the pathogen Dothistroma septosporum responsible for the current outbreak of Dothistroma needle blight (DNB) on native Caledonian Scots pine (Pinus sylvestris) populations in Scotland and evaluated the role played by widespread planting of two exotic pine species in the development of the disease outbreak. We distinguished three races of D. septosporum in Scotland, one of low genetic diversity associated with introduced lodgepole pine (Pinus contorta), one of high diversity probably derived from the DNB epidemic on introduced Corsican pine (Pinus nigra subsp. laricio) in England and a third of intermediate diversity apparently endemic on Caledonian Scots pine. These races differed for both growth rate and exudate production in culture. Planting of exotic pine stands in the UK appears to have facilitated the introduction of two exotic races of D. septosporum into Scotland which now pose a threat to native Caledonian pines both directly and through potential hybridization and introgression with the endemic race. Our results indicate that both removal of exotic species from the vicinity of Caledonian pine populations and restriction of movement of planting material are required to minimize the impact of the current DNB outbreak. They also demonstrate that planting exotic species that are related to native species reduces rather than enhances the resilience of forests to pathogens.}, } @article {pmid29632552, year = {2018}, author = {Cornejo, OE and Hickey, RJ and Suzuki, H and Forney, LJ}, title = {Focusing the diversity of Gardnerella vaginalis through the lens of ecotypes.}, journal = {Evolutionary applications}, volume = {11}, number = {3}, pages = {312-324}, pmid = {29632552}, issn = {1752-4571}, support = {P30 GM103324/GM/NIGMS NIH HHS/United States ; R01 NR015495/NR/NINR NIH HHS/United States ; U19 AI084044/AI/NIAID NIH HHS/United States ; }, abstract = {Gardnerella vaginalis has long been associated with bacterial vaginosis, a condition that increases the risk of women to preterm birth, sexually transmitted infections, and other adverse sequelae. However, G. vaginalis is also commonly found in healthy asymptomatic women of all ages. This raises the question if genetic differences among strains might distinguish potentially pathogenic from commensal strains. To disentangle the diversity of G. vaginalis, we invoked the concept of ecotypes-lineages of genetically and ecologically distinct strains within a named species-to better understand their evolutionary history and identify functional characteristics. We compared the genomes of G. vaginalis to six species in the closely related Bifidobacterium genus and found that G. vaginalis has a large accessory genome relative to Bifidobacterium, including many unique genes possibly involved in metabolism, drug resistance, and virulence. We then performed a comparative genomic analysis of 35 strains of G. vaginalis to infer a phylogeny based on the combined analysis of the core genome, using nucleotide substitution models, and the accessory genome, using gene gain/loss models. With the inferred tree topology, we performed comparisons of functional gene content among lineages that diverged at varying depths in the phylogeny and found significant differences in the representation of genes putatively involved in pathogenicity. Our functional enrichment analysis suggests that some lineages of G. vaginalis may possess enhanced pathogenic capabilities, including genes involved in mucus degradation like sialidases, while others may be commensal strains, lacking many of these pathogenic capabilities. The combined phylogenetic evidence and functional enrichment analysis allowed us to identify distinct ecotypes that have evolved in G. vaginalis as the result of the differential gene gain/loss for specific functions, including the capability to cause disease. We finally discuss how this analysis framework could be used to gain insight into the etiology of bacterial vaginosis and improve diagnosis.}, } @article {pmid29632390, year = {2018}, author = {Zeller, M and Andersen, KG}, title = {Backbone of RNA viruses uncovered.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {182-183}, doi = {10.1038/d41586-018-03923-w}, pmid = {29632390}, issn = {1476-4687}, mesh = {RNA Viruses/*genetics ; RNA, Viral ; Virology ; Viruses/*genetics ; }, } @article {pmid29632389, year = {2018}, author = {Christmann, A and Grill, E}, title = {Peptide signal alerts plants to drought.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {178-179}, doi = {10.1038/d41586-018-03872-4}, pmid = {29632389}, issn = {1476-4687}, mesh = {Abscisic Acid ; *Droughts ; Gene Expression Regulation, Plant ; Peptides ; Plant Proteins/genetics ; *Plants ; Plants, Genetically Modified ; Stress, Physiological ; Water ; }, } @article {pmid29632388, year = {2018}, author = {}, title = {New awards aim to celebrate women in science.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {150}, doi = {10.1038/d41586-018-04323-w}, pmid = {29632388}, issn = {1476-4687}, } @article {pmid29632383, year = {2018}, author = {Gusev, A and Mancuso, N and Won, H and Kousi, M and Finucane, HK and Reshef, Y and Song, L and Safi, A and , and McCarroll, S and Neale, BM and Ophoff, RA and O'Donovan, MC and Crawford, GE and Geschwind, DH and Katsanis, N and Sullivan, PF and Pasaniuc, B and Price, AL}, title = {Transcriptome-wide association study of schizophrenia and chromatin activity yields mechanistic disease insights.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {538-548}, pmid = {29632383}, issn = {1546-1718}, support = {P50 MH094268/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; F32 GM106584/GM/NIGMS NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R01 MH105472/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; P50 MH084053/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; P01 AG002219/AG/NIA NIH HHS/United States ; R01 MH093725/MH/NIMH NIH HHS/United States ; P50 AG005138/AG/NIA NIH HHS/United States ; R01 GM105857/GM/NIGMS NIH HHS/United States ; U01 HG009379/HG/NHGRI NIH HHS/United States ; K99 MH113823/MH/NIMH NIH HHS/United States ; R01 HG009120/HG/NHGRI NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; HHSN271201300031C/MH/NIMH NIH HHS/United States ; S10 OD018164/OD/NIH HHS/United States ; P50 MH066392/MH/NIMH NIH HHS/United States ; R01 MH109978/MH/NIMH NIH HHS/United States ; R01 MH080405/MH/NIMH NIH HHS/United States ; U01 MH109528/MH/NIMH NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; }, abstract = {Genome-wide association studies (GWAS) have identified over 100 risk loci for schizophrenia, but the causal mechanisms remain largely unknown. We performed a transcriptome-wide association study (TWAS) integrating a schizophrenia GWAS of 79,845 individuals from the Psychiatric Genomics Consortium with expression data from brain, blood, and adipose tissues across 3,693 primarily control individuals. We identified 157 TWAS-significant genes, of which 35 did not overlap a known GWAS locus. Of these 157 genes, 42 were associated with specific chromatin features measured in independent samples, thus highlighting potential regulatory targets for follow-up. Suppression of one identified susceptibility gene, mapk3, in zebrafish showed a significant effect on neurodevelopmental phenotypes. Expression and splicing from the brain captured most of the TWAS effect across all genes. This large-scale connection of associations to target genes, tissues, and regulatory features is an essential step in moving toward a mechanistic understanding of GWAS.}, } @article {pmid29632382, year = {2018}, author = {Mahajan, A and Wessel, J and Willems, SM and Zhao, W and Robertson, NR and Chu, AY and Gan, W and Kitajima, H and Taliun, D and Rayner, NW and Guo, X and Lu, Y and Li, M and Jensen, RA and Hu, Y and Huo, S and Lohman, KK and Zhang, W and Cook, JP and Prins, BP and Flannick, J and Grarup, N and Trubetskoy, VV and Kravic, J and Kim, YJ and Rybin, DV and Yaghootkar, H and Müller-Nurasyid, M and Meidtner, K and Li-Gao, R and Varga, TV and Marten, J and Li, J and Smith, AV and An, P and Ligthart, S and Gustafsson, S and Malerba, G and Demirkan, A and Tajes, JF and Steinthorsdottir, V and Wuttke, M and Lecoeur, C and Preuss, M and Bielak, LF and Graff, M and Highland, HM and Justice, AE and Liu, DJ and Marouli, E and Peloso, GM and Warren, HR and , and , and , and Afaq, S and Afzal, S and Ahlqvist, E and Almgren, P and Amin, N and Bang, LB and Bertoni, AG and Bombieri, C and Bork-Jensen, J and Brandslund, I and Brody, JA and Burtt, NP and Canouil, M and Chen, YI and Cho, YS and Christensen, C and Eastwood, SV and Eckardt, KU and Fischer, K and Gambaro, G and Giedraitis, V and Grove, ML and de Haan, HG and Hackinger, S and Hai, Y and Han, S and Tybjærg-Hansen, A and Hivert, MF and Isomaa, B and Jäger, S and Jørgensen, ME and Jørgensen, T and Käräjämäki, A and Kim, BJ and Kim, SS and Koistinen, HA and Kovacs, P and Kriebel, J and Kronenberg, F and Läll, K and Lange, LA and Lee, JJ and Lehne, B and Li, H and Lin, KH and Linneberg, A and Liu, CT and Liu, J and Loh, M and Mägi, R and Mamakou, V and McKean-Cowdin, R and Nadkarni, G and Neville, M and Nielsen, SF and Ntalla, I and Peyser, PA and Rathmann, W and Rice, K and Rich, SS and Rode, L and Rolandsson, O and Schönherr, S and Selvin, E and Small, KS and Stančáková, A and Surendran, P and Taylor, KD and Teslovich, TM and Thorand, B and Thorleifsson, G and Tin, A and Tönjes, A and Varbo, A and Witte, DR and Wood, AR and Yajnik, P and Yao, J and Yengo, L and Young, R and Amouyel, P and Boeing, H and Boerwinkle, E and Bottinger, EP and Chowdhury, R and Collins, FS and Dedoussis, G and Dehghan, A and Deloukas, P and Ferrario, MM and Ferrières, J and Florez, JC and Frossard, P and Gudnason, V and Harris, TB and Heckbert, SR and Howson, JMM and Ingelsson, M and Kathiresan, S and Kee, F and Kuusisto, J and Langenberg, C and Launer, LJ and Lindgren, CM and Männistö, S and Meitinger, T and Melander, O and Mohlke, KL and Moitry, M and Morris, AD and Murray, AD and de Mutsert, R and Orho-Melander, M and Owen, KR and Perola, M and Peters, A and Province, MA and Rasheed, A and Ridker, PM and Rivadineira, F and Rosendaal, FR and Rosengren, AH and Salomaa, V and Sheu, WH and Sladek, R and Smith, BH and Strauch, K and Uitterlinden, AG and Varma, R and Willer, CJ and Blüher, M and Butterworth, AS and Chambers, JC and Chasman, DI and Danesh, J and van Duijn, C and Dupuis, J and Franco, OH and Franks, PW and Froguel, P and Grallert, H and Groop, L and Han, BG and Hansen, T and Hattersley, AT and Hayward, C and Ingelsson, E and Kardia, SLR and Karpe, F and Kooner, JS and Köttgen, A and Kuulasmaa, K and Laakso, M and Lin, X and Lind, L and Liu, Y and Loos, RJF and Marchini, J and Metspalu, A and Mook-Kanamori, D and Nordestgaard, BG and Palmer, CNA and Pankow, JS and Pedersen, O and Psaty, BM and Rauramaa, R and Sattar, N and Schulze, MB and Soranzo, N and Spector, TD and Stefansson, K and Stumvoll, M and Thorsteinsdottir, U and Tuomi, T and Tuomilehto, J and Wareham, NJ and Wilson, JG and Zeggini, E and Scott, RA and Barroso, I and Frayling, TM and Goodarzi, MO and Meigs, JB and Boehnke, M and Saleheen, D and Morris, AP and Rotter, JI and McCarthy, MI}, title = {Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {559-571}, pmid = {29632382}, issn = {1546-1718}, support = {U01 DK085545/DK/NIDDK NIH HHS/United States ; R01 DK098032/DK/NIDDK NIH HHS/United States ; R00 HL130580/HL/NHLBI NIH HHS/United States ; R35 HL135824/HL/NHLBI NIH HHS/United States ; R01 DK062370/DK/NIDDK NIH HHS/United States ; U01 DK105535/DK/NIDDK NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; K24 DK080140/DK/NIDDK NIH HHS/United States ; MC_PC_U127561128//Medical Research Council/United Kingdom ; U01 DK062370/DK/NIDDK NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; P30 DK116074/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; T32 HL007055/HL/NHLBI NIH HHS/United States ; }, abstract = {We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10-7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent 'false leads' with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.}, } @article {pmid29632381, year = {2018}, author = {Vasilevsky, NA and Foster, ED and Engelstad, ME and Carmody, L and Might, M and Chambers, C and Dawkins, HJS and Lewis, J and Della Rocca, MG and Snyder, M and Boerkoel, CF and Rath, A and Terry, SF and Kent, A and Searle, B and Baynam, G and Jones, E and Gavin, P and Bamshad, M and Chong, J and Groza, T and Adams, D and Resnick, AC and Heath, AP and Mungall, C and Holm, IA and Rageth, K and Brownstein, CA and Shefchek, K and McMurry, JA and Robinson, PN and Köhler, S and Haendel, MA}, title = {Plain-language medical vocabulary for precision diagnosis.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {474-476}, pmid = {29632381}, issn = {1546-1718}, support = {R24 OD011883/OD/NIH HHS/United States ; UL1 RR033184/RR/NCRR NIH HHS/United States ; UL1 TR002014/TR/NCATS NIH HHS/United States ; UM1 HG006493/HG/NHGRI NIH HHS/United States ; }, } @article {pmid29632380, year = {2018}, author = {Finucane, HK and Reshef, YA and Anttila, V and Slowikowski, K and Gusev, A and Byrnes, A and Gazal, S and Loh, PR and Lareau, C and Shoresh, N and Genovese, G and Saunders, A and Macosko, E and Pollack, S and , and Perry, JRB and Buenrostro, JD and Bernstein, BE and Raychaudhuri, S and McCarroll, S and Neale, BM and Price, AL}, title = {Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {621-629}, pmid = {29632380}, issn = {1546-1718}, support = {R01 MH094714/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; U01 CA194393/CA/NCI NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; MC_UU_12015/2//Medical Research Council/United Kingdom ; R01 MH105472/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 AR063759/AR/NIAMS NIH HHS/United States ; U01 HG009379/HG/NHGRI NIH HHS/United States ; UH2 AR067677/AR/NIAMS NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; R01 MH109978/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; }, abstract = {We introduce an approach to identify disease-relevant tissues and cell types by analyzing gene expression data together with genome-wide association study (GWAS) summary statistics. Our approach uses stratified linkage disequilibrium (LD) score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We applied our approach to gene expression data from several sources together with GWAS summary statistics for 48 diseases and traits (average N = 169,331) and found significant tissue-specific enrichments (false discovery rate (FDR) < 5%) for 34 traits. In our analysis of multiple tissues, we detected a broad range of enrichments that recapitulated known biology. In our brain-specific analysis, significant enrichments included an enrichment of inhibitory over excitatory neurons for bipolar disorder, and excitatory over inhibitory neurons for schizophrenia and body mass index. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signals.}, } @article {pmid29632379, year = {2018}, author = {Small, KS and Todorčević, M and Civelek, M and El-Sayed Moustafa, JS and Wang, X and Simon, MM and Fernandez-Tajes, J and Mahajan, A and Horikoshi, M and Hugill, A and Glastonbury, CA and Quaye, L and Neville, MJ and Sethi, S and Yon, M and Pan, C and Che, N and Viñuela, A and Tsai, PC and Nag, A and Buil, A and Thorleifsson, G and Raghavan, A and Ding, Q and Morris, AP and Bell, JT and Thorsteinsdottir, U and Stefansson, K and Laakso, M and Dahlman, I and Arner, P and Gloyn, AL and Musunuru, K and Lusis, AJ and Cox, RD and Karpe, F and McCarthy, MI}, title = {Regulatory variants at KLF14 influence type 2 diabetes risk via a female-specific effect on adipocyte size and body composition.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {572-580}, pmid = {29632379}, issn = {1546-1718}, support = {MR/L020149/1//Medical Research Council/United Kingdom ; P01 HL028481/HL/NHLBI NIH HHS/United States ; U01 DK105535/DK/NIDDK NIH HHS/United States ; MR/J010642/1//Medical Research Council/United Kingdom ; R01 DK099571/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R01 AG033067/AG/NIA NIH HHS/United States ; R00 HL121172/HL/NHLBI NIH HHS/United States ; MC_U142661184//Medical Research Council/United Kingdom ; }, abstract = {Individual risk of type 2 diabetes (T2D) is modified by perturbations to the mass, distribution and function of adipose tissue. To investigate the mechanisms underlying these associations, we explored the molecular, cellular and whole-body effects of T2D-associated alleles near KLF14. We show that KLF14 diabetes-risk alleles act in adipose tissue to reduce KLF14 expression and modulate, in trans, the expression of 385 genes. We demonstrate, in human cellular studies, that reduced KLF14 expression increases pre-adipocyte proliferation but disrupts lipogenesis, and in mice, that adipose tissue-specific deletion of Klf14 partially recapitulates the human phenotype of insulin resistance, dyslipidemia and T2D. We show that carriers of the KLF14 T2D risk allele shift body fat from gynoid stores to abdominal stores and display a marked increase in adipocyte cell size, and that these effects on fat distribution, and the T2D association, are female specific. The metabolic risk associated with variation at this imprinted locus depends on the sex both of the subject and of the parent from whom the risk allele derives.}, } @article {pmid29632378, year = {2018}, author = {Kim, J and Minna, JD}, title = {Evaluating tumor-suppressor gene combinations.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {480-482}, doi = {10.1038/s41588-018-0095-y}, pmid = {29632378}, issn = {1546-1718}, } @article {pmid29632377, year = {2018}, author = {van Blitterswijk, M and Rademakers, R}, title = {Repeat expansions in myoclonic epilepsy.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {477-478}, doi = {10.1038/s41588-018-0093-0}, pmid = {29632377}, issn = {1546-1718}, } @article {pmid29632376, year = {2018}, author = {Sadhu, MJ and Bloom, JS and Day, L and Siegel, JJ and Kosuri, S and Kruglyak, L}, title = {Highly parallel genome variant engineering with CRISPR-Cas9.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {510-514}, pmid = {29632376}, issn = {1546-1718}, support = {DP2 GM114829/GM/NIGMS NIH HHS/United States ; F32 GM116318/GM/NIGMS NIH HHS/United States ; R01 GM102308/GM/NIGMS NIH HHS/United States ; }, abstract = {Understanding the functional effects of DNA sequence variants is of critical importance for studies of basic biology, evolution, and medical genetics; however, measuring these effects in a high-throughput manner is a major challenge. One promising avenue is precise editing with the CRISPR-Cas9 system, which allows for generation of DNA double-strand breaks (DSBs) at genomic sites matching the targeting sequence of a guide RNA (gRNA). Recent studies have used CRISPR libraries to generate many frameshift mutations genome wide through faulty repair of CRISPR-directed breaks by nonhomologous end joining (NHEJ) 1 . Here, we developed a CRISPR-library-based approach for highly efficient and precise genome-wide variant engineering. We used our method to examine the functional consequences of premature-termination codons (PTCs) at different locations within all annotated essential genes in yeast. We found that most PTCs were highly deleterious unless they occurred close to the 3' end of the gene and did not affect an annotated protein domain. Unexpectedly, we discovered that some putatively essential genes are dispensable, whereas others have large dispensable regions. This approach can be used to profile the effects of large classes of variants in a high-throughput manner.}, } @article {pmid29632375, year = {2018}, author = {}, title = {FAIR to the community.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {473}, doi = {10.1038/s41588-018-0103-2}, pmid = {29632375}, issn = {1546-1718}, } @article {pmid29632370, year = {2018}, author = {Haddock, E and Feldmann, F and Hawman, DW and Zivcec, M and Hanley, PW and Saturday, G and Scott, DP and Thomas, T and Korva, M and Avšič-Županc, T and Safronetz, D and Feldmann, H}, title = {A cynomolgus macaque model for Crimean-Congo haemorrhagic fever.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {556-562}, doi = {10.1038/s41564-018-0141-7}, pmid = {29632370}, issn = {2058-5276}, abstract = {Crimean-Congo haemorrhagic fever (CCHF) is the most medically significant tick-borne disease, being widespread in the Middle East, Asia, Africa and parts of Europe 1 . Increasing case numbers, westerly movement and broadly ranging case fatality rates substantiate the concern of CCHF as a public health threat. Ixodid ticks of the genus Hyalomma are the vector for CCHF virus (CCHFV), an arbovirus in the genus Orthonairovirus of the family Nairoviridae. CCHFV naturally infects numerous wild and domestic animals via tick bite without causing obvious disease2,3. Severe disease occurs only in humans and transmission usually happens through tick bite or contact with infected animals or humans. The only CCHF disease model is a subset of immunocompromised mice4-6. Here, we show that following CCHFV infection, cynomolgus macaques exhibited hallmark signs of human CCHF with remarkably similar viral dissemination, organ pathology and disease progression. Histopathology showed infection of hepatocytes, endothelial cells and monocytes and fatal outcome seemed associated with endothelial dysfunction manifesting in a clinical shock syndrome with coagulopathy. This non-human primate model will be an invaluable asset for CCHFV countermeasures development.}, } @article {pmid29632369, year = {2018}, author = {Burkinshaw, BJ and Liang, X and Wong, M and Le, ANH and Lam, L and Dong, TG}, title = {A type VI secretion system effector delivery mechanism dependent on PAAR and a chaperone-co-chaperone complex.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {632-640}, doi = {10.1038/s41564-018-0144-4}, pmid = {29632369}, issn = {2058-5276}, abstract = {The type VI secretion system (T6SS) is used by many Gram-negative bacteria as a molecular weapon to modulate neighbouring bacterial and eukaryotic cells, thereby affecting the dynamics of community structure in multiple species environments. The T6SS injects its inner-needle Hcp tube, the sharpening tip complex consisting of VgrG and PAAR, and toxic effectors into neighbouring cells. Its functions are largely determined by the activities of its delivered effectors. Six mechanisms of effector delivery have been described: two mediated by the inner tube and the others mediated by the VgrG and PAAR tip complex. Here, we report an additional effector delivery mechanism that relies on interaction with a chaperone complex and a PAAR protein as a carrier. The Pseudomonas aeruginosa PAO1 TOX-REase-5 domain-containing effector TseT directly interacts with PAAR4 and the chaperone TecT for delivery, and an immunity protein, TsiT, for protection from its toxicity. TecT forms a complex with its co-chaperone, co-TecT, which is disrupted by the carboxy-terminal tail of PAAR4. In addition, we delineate a complex, multilayered competitive process that dictates effector trafficking. PAAR delivery provides an additional tool for engineering cargo protein translocation.}, } @article {pmid29632368, year = {2018}, author = {Gopinath, S and Kim, MV and Rakib, T and Wong, PW and van Zandt, M and Barry, NA and Kaisho, T and Goodman, AL and Iwasaki, A}, title = {Topical application of aminoglycoside antibiotics enhances host resistance to viral infections in a microbiota-independent manner.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {611-621}, pmid = {29632368}, issn = {2058-5276}, support = {R01 AI054359/AI/NIAID NIH HHS/United States ; R01 EB000487/EB/NIBIB NIH HHS/United States ; R21 AI131284/AI/NIAID NIH HHS/United States ; R56 AI125504/AI/NIAID NIH HHS/United States ; }, abstract = {Antibiotics are widely used to treat infections in humans. However, the impact of antibiotic use on host cells is understudied. Here we identify an antiviral effect of commonly used aminoglycoside antibiotics. We show that topical mucosal application of aminoglycosides prophylactically increased host resistance to a broad range of viral infections including herpes simplex viruses, influenza A virus and Zika virus. Aminoglycoside treatment also reduced viral replication in primary human cells. This antiviral activity was independent of the microbiota, because aminoglycoside treatment protected germ-free mice. Microarray analysis uncovered a marked upregulation of transcripts for interferon-stimulated genes (ISGs) following aminoglycoside application. ISG induction was mediated by Toll-like receptor 3, and required Toll/interleukin-1-receptor-domain-containing adapter-inducing interferon-β signalling adaptor, and Interferon regulatory factors 3 and 7, transcription factors that promote ISG expression. XCR1+ dendritic cells, which uniquely express Toll-like receptor 3, were recruited to the vaginal mucosa upon aminoglycoside treatment and were required for ISG induction. These results highlight an unexpected ability of aminoglycoside antibiotics to confer broad antiviral resistance in vivo.}, } @article {pmid29632367, year = {2018}, author = {Novy, K and Kilcher, S and Omasits, U and Bleck, CKE and Beerli, C and Vowinckel, J and Martin, CK and Syedbasha, M and Maiolica, A and White, I and Mercer, J and Wollscheid, B}, title = {Proteotype profiling unmasks a viral signalling network essential for poxvirus assembly and transcriptional competence.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {588-599}, doi = {10.1038/s41564-018-0142-6}, pmid = {29632367}, issn = {2058-5276}, abstract = {To orchestrate context-dependent signalling programmes, poxviruses encode two dual-specificity enzymes, the F10 kinase and the H1 phosphatase. These signalling mediators are essential for poxvirus production, yet their substrate profiles and systems-level functions remain enigmatic. Using a phosphoproteomic screen of cells infected with wild-type, F10 and H1 mutant vaccinia viruses, we systematically defined the viral signalling network controlled by these enzymes. Quantitative cross-comparison revealed 33 F10 and/or H1 phosphosites within 17 viral proteins. Using this proteotype dataset to inform genotype-phenotype relationships, we found that H1-deficient virions harbour a hidden hypercleavage phenotype driven by reversible phosphorylation of the virus protease I7 (S134). Quantitative phosphoproteomic profiling further revealed that the phosphorylation-dependent activity of the viral early transcription factor, A7 (Y367), underlies the transcription-deficient phenotype of H1 mutant virions. Together, these results highlight the utility of combining quantitative proteotype screens with mutant viruses to uncover proteotype-phenotype-genotype relationships that are masked by classical genetic studies.}, } @article {pmid29632366, year = {2018}, author = {Yin, M and Yan, Z and Li, X}, title = {Structural insight into the assembly of the type II secretion system pilotin-secretin complex from enterotoxigenic Escherichia coli.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {581-587}, doi = {10.1038/s41564-018-0148-0}, pmid = {29632366}, issn = {2058-5276}, abstract = {Secretin is a large outer-membrane channel found in secretion systems of Gram-negative bacteria, facilitating the last step for transfer of proteins into the extracellular environment. In the type II secretion system, a lipoprotein called pilotin is essential to bind and target its corresponding secretin to the outer membrane. However, there is only limited structural information available about the interaction and assembly of the pilotin-secretin complex. Here we report the first near-atomic-resolution structure of a full-length Vibrio-type pilotin-secretin (AspS-GspD) complex from enterotoxigenic Escherichia coli by cryo-electron microscopy, which reveals the detailed assembly mode of the full-length pilotin-secretin complex. The AspS subunits attach to the secretin channel surface with a 15:15 stoichiometric ratio to GspD subunits, and insert their amino terminus into the outer membrane. The AspS subunits interact with all three secondary structural elements of the S domain of GspD, including strong interaction with the carboxy-terminal α-helix and weak interactions with another two elements, an α-helix and a loop. These structural and biochemical details provide a deeper insight to pilotin-secretin interaction and their assembly mode.}, } @article {pmid29632365, year = {2018}, author = {Barrangou, R and van der Oost, J}, title = {Mining for novel bacterial defence systems.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {535-536}, doi = {10.1038/s41564-018-0149-z}, pmid = {29632365}, issn = {2058-5276}, } @article {pmid29632357, year = {2018}, author = {O'Connor, EA and Cornwallis, CK and Hasselquist, D and Nilsson, JÅ and Westerdahl, H}, title = {The evolution of immunity in relation to colonization and migration.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {841-849}, doi = {10.1038/s41559-018-0509-3}, pmid = {29632357}, issn = {2397-334X}, abstract = {Colonization and migration have a crucial effect on patterns of biodiversity, with disease predicted to play an important role in these processes. However, evidence of the effect of pathogens on broad patterns of colonization and migration is limited. Here, using phylogenetic analyses of 1,311 species of Afro-Palaearctic songbirds, we show that colonization events from regions of high (sub-Saharan Africa) to low (the Palaearctic) pathogen diversity were up to 20 times more frequent than the reverse, and that migration has evolved 3 times more frequently from African- as opposed to Palaearctic-resident species. We also found that resident species that colonized the Palaearctic from Africa, as well as African species that evolved long-distance migration to breed in the Palaearctic, have reduced diversity of key immune genes associated with pathogen recognition (major histocompatibility complex class I). These results suggest that changes in the pathogen community that occur during colonization and migration shape the evolution of the immune system, potentially by adjusting the trade-off between the benefits of extensive pathogen recognition and the costs of immunopathology that result from high major histocompatibility complex class I diversity.}, } @article {pmid29632356, year = {2018}, author = {Chazdon, RL}, title = {Protecting intact forests requires holistic approaches.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {915}, doi = {10.1038/s41559-018-0546-y}, pmid = {29632356}, issn = {2397-334X}, } @article {pmid29632355, year = {2018}, author = {Henry, DO}, title = {Joining the dots.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {767-768}, doi = {10.1038/s41559-018-0539-x}, pmid = {29632355}, issn = {2397-334X}, } @article {pmid29632354, year = {2018}, author = {Rodriguez-Beltran, J and Hernandez-Beltran, JCR and DelaFuente, J and Escudero, JA and Fuentes-Hernandez, A and MacLean, RC and Peña-Miller, R and San Millan, A}, title = {Multicopy plasmids allow bacteria to escape from fitness trade-offs during evolutionary innovation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {873-881}, pmid = {29632354}, issn = {2397-334X}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Understanding the mechanisms governing innovation is a central element of evolutionary theory. Novel traits usually arise through mutations in existing genes, but trade-offs between new and ancestral protein functions are pervasive and constrain the evolution of innovation. Classical models posit that evolutionary innovation circumvents the constraints imposed by trade-offs through genetic amplifications, which provide functional redundancy. Bacterial multicopy plasmids provide a paradigmatic example of genetic amplification, yet their role in evolutionary innovation remains largely unexplored. Here, we reconstructed the evolution of a new trait encoded in a multicopy plasmid using TEM-1 β-lactamase as a model system. Through a combination of theory and experimentation, we show that multicopy plasmids promote the coexistence of ancestral and novel traits for dozens of generations, allowing bacteria to escape the evolutionary constraints imposed by trade-offs. Our results suggest that multicopy plasmids are excellent platforms for evolutionary innovation, contributing to explain their extreme abundance in bacteria.}, } @article {pmid29632353, year = {2018}, author = {Bastir, M}, title = {Pulling faces.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {923-924}, doi = {10.1038/s41559-018-0550-2}, pmid = {29632353}, issn = {2397-334X}, } @article {pmid29632352, year = {2018}, author = {Groucutt, HS and Grün, R and Zalmout, IAS and Drake, NA and Armitage, SJ and Candy, I and Clark-Wilson, R and Louys, J and Breeze, PS and Duval, M and Buck, LT and Kivell, TL and Pomeroy, E and Stephens, NB and Stock, JT and Stewart, M and Price, GJ and Kinsley, L and Sung, WW and Alsharekh, A and Al-Omari, A and Zahir, M and Memesh, AM and Abdulshakoor, AJ and Al-Masari, AM and Bahameem, AA and Al Murayyi, KMS and Zahrani, B and Scerri, ELM and Petraglia, MD}, title = {Homo sapiens in Arabia by 85,000 years ago.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {800-809}, pmid = {29632352}, issn = {2397-334X}, abstract = {Understanding the timing and character of the expansion of Homo sapiens out of Africa is critical for inferring the colonization and admixture processes that underpin global population history. It has been argued that dispersal out of Africa had an early phase, particularly ~130-90 thousand years ago (ka), that reached only the East Mediterranean Levant, and a later phase, ~60-50 ka, that extended across the diverse environments of Eurasia to Sahul. However, recent findings from East Asia and Sahul challenge this model. Here we show that H. sapiens was in the Arabian Peninsula before 85 ka. We describe the Al Wusta-1 (AW-1) intermediate phalanx from the site of Al Wusta in the Nefud desert, Saudi Arabia. AW-1 is the oldest directly dated fossil of our species outside Africa and the Levant. The palaeoenvironmental context of Al Wusta demonstrates that H. sapiens using Middle Palaeolithic stone tools dispersed into Arabia during a phase of increased precipitation driven by orbital forcing, in association with a primarily African fauna. A Bayesian model incorporating independent chronometric age estimates indicates a chronology for Al Wusta of ~95-86 ka, which we correlate with a humid episode in the later part of Marine Isotope Stage 5 known from various regional records. Al Wusta shows that early dispersals were more spatially and temporally extensive than previously thought. Early H. sapiens dispersals out of Africa were not limited to winter rainfall-fed Levantine Mediterranean woodlands immediately adjacent to Africa, but extended deep into the semi-arid grasslands of Arabia, facilitated by periods of enhanced monsoonal rainfall.}, } @article {pmid29632351, year = {2018}, author = {Brandt, M and Wigneron, JP and Chave, J and Tagesson, T and Penuelas, J and Ciais, P and Rasmussen, K and Tian, F and Mbow, C and Al-Yaari, A and Rodriguez-Fernandez, N and Schurgers, G and Zhang, W and Chang, J and Kerr, Y and Verger, A and Tucker, C and Mialon, A and Rasmussen, LV and Fan, L and Fensholt, R}, title = {Satellite passive microwaves reveal recent climate-induced carbon losses in African drylands.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {827-835}, doi = {10.1038/s41559-018-0530-6}, pmid = {29632351}, issn = {2397-334X}, abstract = {The African continent is facing one of the driest periods in the past three decades as well as continued deforestation. These disturbances threaten vegetation carbon (C) stocks and highlight the need for improved capabilities of monitoring large-scale aboveground carbon stock dynamics. Here we use a satellite dataset based on vegetation optical depth derived from low-frequency passive microwaves (L-VOD) to quantify annual aboveground biomass-carbon changes in sub-Saharan Africa between 2010 and 2016. L-VOD is shown not to saturate over densely vegetated areas. The overall net change in drylands (53% of the land area) was -0.05 petagrams of C per year (Pg C yr-1) associated with drying trends, and a net change of -0.02 Pg C yr-1 was observed in humid areas. These trends reflect a high inter-annual variability with a very dry year in 2015 (net change, -0.69 Pg C) with about half of the gross losses occurring in drylands. This study demonstrates, first, the applicability of L-VOD to monitor the dynamics of carbon loss and gain due to weather variations, and second, the importance of the highly dynamic and vulnerable carbon pool of dryland savannahs for the global carbon balance, despite the relatively low carbon stock per unit area.}, } @article {pmid29632350, year = {2018}, author = {Pearce, DG and Bonneau, A}, title = {Trouble on the dating scene.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {925-926}, doi = {10.1038/s41559-018-0540-4}, pmid = {29632350}, issn = {2397-334X}, } @article {pmid29632349, year = {2018}, author = {Godinho, RM and Spikins, P and O'Higgins, P}, title = {Supraorbital morphology and social dynamics in human evolution.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {956-961}, doi = {10.1038/s41559-018-0528-0}, pmid = {29632349}, issn = {2397-334X}, abstract = {Uniquely, with respect to Middle Pleistocene hominins, anatomically modern humans do not possess marked browridges, and have a more vertical forehead with mobile eyebrows that play a key role in social signalling and communication. The presence and variability of browridges in archaic Homo species and their absence in ourselves have led to debate concerning their morphogenesis and function, with two main hypotheses being put forward: that browridge morphology is the result of the spatial relationship between the orbits and the brain case; and that browridge morphology is significantly impacted by biting mechanics. Here, we virtually manipulate the browridge morphology of an archaic hominin (Kabwe 1), showing that it is much larger than the minimum required to fulfil spatial demands and that browridge size has little impact on mechanical performance during biting. As browridge morphology in this fossil is not driven by spatial and mechanical requirements alone, the role of the supraorbital region in social communication is a potentially significant factor. We propose that conversion of the large browridges of our immediate ancestors to a more vertical frontal bone in modern humans allowed highly mobile eyebrows to display subtle affiliative emotions.}, } @article {pmid29632312, year = {2018}, author = {Verma, R and Reichermeier, KM and Burroughs, AM and Oania, RS and Reitsma, JM and Aravind, L and Deshaies, RJ}, title = {Vms1 and ANKZF1 peptidyl-tRNA hydrolases release nascent chains from stalled ribosomes.}, journal = {Nature}, volume = {557}, number = {7705}, pages = {446-451}, pmid = {29632312}, issn = {1476-4687}, support = {Z99 LM999999/NULL/Intramural NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Biocatalysis ; Carboxylic Ester Hydrolases/chemistry/genetics/*metabolism ; Carrier Proteins/chemistry/genetics/*metabolism ; Catalytic Domain/genetics ; Glutamine/genetics/metabolism ; Humans ; Nucleocytoplasmic Transport Proteins/metabolism ; Point Mutation ; Proteasome Endopeptidase Complex/metabolism ; RNA, Transfer/metabolism ; RNA-Binding Proteins/metabolism ; Ribosome Subunits, Large, Eukaryotic/metabolism ; Ribosomes/*metabolism ; Saccharomyces cerevisiae/cytology/*enzymology/metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Staphylococcal Protein A/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; Valosin Containing Protein/metabolism ; Vesicular Transport Proteins/metabolism ; }, abstract = {Ribosomal surveillance pathways scan for ribosomes that are transiently paused or terminally stalled owing to structural elements in mRNAs or nascent chain sequences1, 2. Some stalls in budding yeast are sensed by the GTPase Hbs1, which loads Dom34, a catalytically inactive member of the archaeo-eukaryotic release factor 1 superfamily. Hbs1-Dom34 and the ATPase Rli1 dissociate stalled ribosomes into 40S and 60S subunits. However, the 60S subunits retain the peptidyl-tRNA nascent chains, which recruit the ribosome quality control complex that consists of Rqc1-Rqc2-Ltn1-Cdc48-Ufd1-Npl4. Nascent chains ubiquitylated by the E3 ubiquitin ligase Ltn1 are extracted from the 60S subunit by the ATPase Cdc48-Ufd1-Npl4 and presented to the 26S proteasome for degradation3-9. Failure to degrade the nascent chains leads to protein aggregation and proteotoxic stress in yeast and neurodegeneration in mice10-14. Despite intensive investigations on the ribosome quality control pathway, it is not known how the tRNA is hydrolysed from the ubiquitylated nascent chain before its degradation. Here we show that the Cdc48 adaptor Vms1 is a peptidyl-tRNA hydrolase. Similar to classical eukaryotic release factor 1, Vms1 activity is dependent on a conserved catalytic glutamine. Evolutionary analysis indicates that yeast Vms1 is the founding member of a clade of eukaryotic release factor 1 homologues that we designate the Vms1-like release factor 1 clade.}, } @article {pmid29632271, year = {2018}, author = {Wheeler, RJ and Hyman, AA}, title = {Controlling compartmentalization by non-membrane-bound organelles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632271}, issn = {1471-2970}, abstract = {Compartmentalization is a characterizing feature of complexity in cells, used to organize their biochemistry. Membrane-bound organelles are most widely known, but non-membrane-bound liquid organelles also exist. These have recently been shown to form by phase separation of specific types of proteins known as scaffolds. This forms two phases: a condensate that is enriched in scaffold protein separated by a phase boundary from the cytoplasm or nucleoplasm with a low concentration of the scaffold protein. Phase separation is well known for synthetic polymers, but also appears important in cells. Here, we review the properties of proteins important for forming these non-membrane-bound organelles, focusing on the energetically favourable interactions that drive condensation. On this basis we make qualitative predictions about how cells may control compartmentalization by condensates; the partition of specific molecules to a condensate; the control of condensation and dissolution of condensates; and the regulation of condensate nucleation. There are emerging data supporting many of these predictions, although future results may prove incorrect. It appears that many molecules may have the ability to modulate condensate formation, making condensates a potential target for future therapeutics. The emerging properties of condensates are fundamentally unlike the properties of membrane-bound organelles. They have the capacity to rapidly integrate cellular events and act as a new class of sensors for internal and external environments.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632270, year = {2018}, author = {Saha, S and Nagy, TL and Weiner, OD}, title = {Joining forces: crosstalk between biochemical signalling and physical forces orchestrates cellular polarity and dynamics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632270}, issn = {1471-2970}, support = {R35 GM118167/GM/NIGMS NIH HHS/United States ; T32 GM067547/GM/NIGMS NIH HHS/United States ; }, abstract = {Dynamic processes like cell migration and morphogenesis emerge from the self-organized interaction between signalling and cytoskeletal rearrangements. How are these molecular to sub-cellular scale processes integrated to enable cell-wide responses? A growing body of recent studies suggest that forces generated by cytoskeletal dynamics and motor activity at the cellular or tissue scale can organize processes ranging from cell movement, polarity and division to the coordination of responses across fields of cells. To do so, forces not only act mechanically but also engage with biochemical signalling. Here, we review recent advances in our understanding of this dynamic crosstalk between biochemical signalling, self-organized cortical actomyosin dynamics and physical forces with a special focus on the role of membrane tension in integrating cellular motility.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632269, year = {2018}, author = {Sych, T and Mély, Y and Römer, W}, title = {Lipid self-assembly and lectin-induced reorganization of the plasma membrane.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632269}, issn = {1471-2970}, abstract = {The plasma membrane represents an outstanding example of self-organization in biology. It plays a vital role in protecting the integrity of the cell interior and regulates meticulously the import and export of diverse substances. Its major building blocks are proteins and lipids, which self-assemble to a fluid lipid bilayer driven mainly by hydrophobic forces. Even if the plasma membrane appears-globally speaking-homogeneous at physiological temperatures, the existence of specialized nano- to micrometre-sized domains of raft-type character within cellular and synthetic membrane systems has been reported. It is hypothesized that these domains are the origin of a plethora of cellular processes, such as signalling or vesicular trafficking. This review intends to highlight the driving forces of lipid self-assembly into a bilayer membrane and the formation of small, transient domains within the plasma membrane. The mechanisms of self-assembly depend on several factors, such as the lipid composition of the membrane and the geometry of lipids. Moreover, the dynamics and organization of glycosphingolipids into nanometre-sized clusters will be discussed, also in the context of multivalent lectins, which cluster several glycosphingolipid receptor molecules and thus create an asymmetric stress between the two membrane leaflets, leading to tubular plasma membrane invaginations.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632268, year = {2018}, author = {Yang, Y and Wu, M}, title = {Rhythmicity and waves in the cortex of single cells.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632268}, issn = {1471-2970}, abstract = {Emergence of dynamic patterns in the form of oscillations and waves on the cortex of single cells is a fascinating and enigmatic phenomenon. Here we outline various theoretical frameworks used to model pattern formation with the goal of reducing complex, heterogeneous patterns into key parameters that are biologically tractable. We also review progress made in recent years on the quantitative and molecular definitions of these terms, which we believe have begun to transform single-cell dynamic patterns from a purely observational and descriptive subject to more mechanistic studies. Specifically, we focus on the nature of local excitable and oscillation events, their spatial couplings leading to propagating waves and the role of active membrane. Instead of arguing for their functional importance, we prefer to consider such patterns as basic properties of dynamic systems. We discuss how knowledge of these patterns could be used to dissect the structure of cellular organization and how the network-centric view could help define cellular functions as transitions between different dynamical states. Last, we speculate on how these patterns could encode temporal and spatial information.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632267, year = {2018}, author = {Gov, NS}, title = {Guided by curvature: shaping cells by coupling curved membrane proteins and cytoskeletal forces.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632267}, issn = {1471-2970}, abstract = {Eukaryote cells have flexible membranes that allow them to have a variety of dynamical shapes. The shapes of the cells serve important biological functions, both for cells within an intact tissue, and during embryogenesis and cellular motility. How cells control their shapes and the structures that they form on their surface has been a subject of intensive biological research, exposing the building blocks that cells use to deform their membranes. These processes have also drawn the interest of theoretical physicists, aiming to develop models based on physics, chemistry and nonlinear dynamics. Such models explore quantitatively different possible mechanisms that the cells can employ to initiate the spontaneous formation of shapes and patterns on their membranes. We review here theoretical work where one such class of mechanisms was investigated: the coupling between curved membrane proteins, and the cytoskeletal forces that they recruit. Theory indicates that this coupling gives rise to a rich variety of membrane shapes and dynamics, while experiments indicate that this mechanism appears to drive many cellular shape changes.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632266, year = {2018}, author = {Dasbiswas, K and Hu, S and Schnorrer, F and Safran, SA and Bershadsky, AD}, title = {Ordering of myosin II filaments driven by mechanical forces: experiments and theory.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632266}, issn = {1471-2970}, abstract = {Myosin II filaments form ordered superstructures in both cross-striated muscle and non-muscle cells. In cross-striated muscle, myosin II (thick) filaments, actin (thin) filaments and elastic titin filaments comprise the stereotypical contractile units of muscles called sarcomeres. Linear chains of sarcomeres, called myofibrils, are aligned laterally in registry to form cross-striated muscle cells. The experimentally observed dependence of the registered organization of myofibrils on extracellular matrix elasticity has been proposed to arise from the interactions of sarcomeric contractile elements (considered as force dipoles) through the matrix. Non-muscle cells form small bipolar filaments built of less than 30 myosin II molecules. These filaments are associated in registry forming superstructures ('stacks') orthogonal to actin filament bundles. Formation of myosin II filament stacks requires the myosin II ATPase activity and function of the actin filament crosslinking, polymerizing and depolymerizing proteins. We propose that the myosin II filaments embedded into elastic, intervening actin network (IVN) function as force dipoles that interact attractively through the IVN. This is in analogy with the theoretical picture developed for myofibrils where the elastic medium is now the actin cytoskeleton itself. Myosin stack formation in non-muscle cells provides a novel mechanism for the self-organization of the actin cytoskeleton at the level of the entire cell.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632265, year = {2018}, author = {Saha, T and Galic, M}, title = {Self-organization across scales: from molecules to organisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632265}, issn = {1471-2970}, abstract = {Creating ordered structures from chaotic environments is at the core of biological processes at the subcellular, cellular and organismic level. In this perspective, we explore the physical as well as biological features of two prominent concepts driving self-organization, namely phase transition and reaction-diffusion, before closing with a discussion on open questions and future challenges associated with studying self-organizing systems.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632264, year = {2018}, author = {Alim, K}, title = {Fluid flows shaping organism morphology.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632264}, issn = {1471-2970}, abstract = {A dynamic self-organized morphology is the hallmark of network-shaped organisms like slime moulds and fungi. Organisms continuously reorganize their flexible, undifferentiated body plans to forage for food. Among these organisms the slime mould Physarum polycephalum has emerged as a model to investigate how an organism can self-organize their extensive networks and act as a coordinated whole. Cytoplasmic fluid flows flowing through the tubular networks have been identified as the key driver of morphological dynamics. Inquiring how fluid flows can shape living matter from small to large scales opens up many new avenues for research. This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632263, year = {2018}, author = {Wettmann, L and Kruse, K}, title = {The Min-protein oscillations in Escherichia coli: an example of self-organized cellular protein waves.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632263}, issn = {1471-2970}, abstract = {In the rod-shaped bacterium Escherichia coli, selection of the cell centre as the division site involves pole-to-pole oscillations of the proteins MinC, MinD and MinE. This spatio-temporal pattern emerges from interactions among the Min proteins and with the cytoplasmic membrane. Combining experimental studies in vivo and in vitro together with theoretical analysis has led to a fairly good understanding of Min-protein self-organization. In different geometries, the system can, in addition to standing waves, also produce travelling planar and spiral waves as well as coexisting stable stationary distributions. Today it stands as one of the best-studied examples of cellular self-organization of proteins.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632262, year = {2018}, author = {Isogai, T and Danuser, G}, title = {Discovery of functional interactions among actin regulators by analysis of image fluctuations in an unperturbed motile cell system.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632262}, issn = {1471-2970}, support = {R01 GM071868/GM/NIGMS NIH HHS/United States ; }, abstract = {Cell migration is driven by propulsive forces derived from polymerizing actin that pushes and extends the plasma membrane. The underlying actin network is constantly undergoing adaptation to new mechano-chemical environments and intracellular conditions. As such, mechanisms that regulate actin dynamics inherently contain multiple feedback loops and redundant pathways. Given the highly adaptable nature of such a system, studies that use only perturbation experiments (e.g. knockdowns, overexpression, pharmacological activation/inhibition, etc.) are challenged by the nonlinearity and redundancy of the pathway. In these pathway configurations, perturbation experiments at best describe the function(s) of a molecular component in an adapting (e.g. acutely drug-treated) or fully adapted (e.g. permanent gene silenced) cell system, where the targeted component now resides in a non-native equilibrium. Here, we propose how quantitative live-cell imaging and analysis of constitutive fluctuations of molecular activities can overcome these limitations. We highlight emerging actin filament barbed-end biology as a prime example of a complex, nonlinear molecular process that requires a fluctuation analytic approach, especially in an unperturbed cellular system, to decipher functional interactions of barbed-end regulators, actin polymerization and membrane protrusion.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632261, year = {2018}, author = {Halatek, J and Brauns, F and Frey, E}, title = {Self-organization principles of intracellular pattern formation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632261}, issn = {1471-2970}, abstract = {Dynamic patterning of specific proteins is essential for the spatio-temporal regulation of many important intracellular processes in prokaryotes, eukaryotes and multicellular organisms. The emergence of patterns generated by interactions of diffusing proteins is a paradigmatic example for self-organization. In this article, we review quantitative models for intracellular Min protein patterns in Escherichia coli, Cdc42 polarization in Saccharomyces cerevisiae and the bipolar PAR protein patterns found in Caenorhabditis elegans By analysing the molecular processes driving these systems we derive a theoretical perspective on general principles underlying self-organized pattern formation. We argue that intracellular pattern formation is not captured by concepts such as 'activators', 'inhibitors' or 'substrate depletion'. Instead, intracellular pattern formation is based on the redistribution of proteins by cytosolic diffusion, and the cycling of proteins between distinct conformational states. Therefore, mass-conserving reaction-diffusion equations provide the most appropriate framework to study intracellular pattern formation. We conclude that directed transport, e.g. cytosolic diffusion along an actively maintained cytosolic gradient, is the key process underlying pattern formation. Thus the basic principle of self-organization is the establishment and maintenance of directed transport by intracellular protein dynamics.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632260, year = {2018}, author = {Kayser, J and Schreck, CF and Yu, Q and Gralka, M and Hallatschek, O}, title = {Emergence of evolutionary driving forces in pattern-forming microbial populations.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632260}, issn = {1471-2970}, support = {R01 GM115851/GM/NIGMS NIH HHS/United States ; }, abstract = {Evolutionary dynamics are controlled by a number of driving forces, such as natural selection, random genetic drift and dispersal. In this perspective article, we aim to emphasize that these forces act at the population level, and that it is a challenge to understand how they emerge from the stochastic and deterministic behaviour of individual cells. Even the most basic steric interactions between neighbouring cells can couple evolutionary outcomes of otherwise unrelated individuals, thereby weakening natural selection and enhancing random genetic drift. Using microbial examples of varying degrees of complexity, we demonstrate how strongly cell-cell interactions influence evolutionary dynamics, especially in pattern-forming systems. As pattern formation itself is subject to evolution, we propose to study the feedback between pattern formation and evolutionary dynamics, which could be key to predicting and potentially steering evolutionary processes. Such an effort requires extending the systems biology approach from the cellular to the population scale.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632259, year = {2018}, author = {Sheftel, H and Szekely, P and Mayo, A and Sella, G and Alon, U}, title = {Evolutionary trade-offs and the structure of polymorphisms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632259}, issn = {1471-2970}, support = {R01 GM115889/GM/NIGMS NIH HHS/United States ; }, abstract = {Populations of organisms show genetic differences called polymorphisms. Understanding the effects of polymorphisms is important for biology and medicine. Here, we ask which polymorphisms occur at high frequency when organisms evolve under trade-offs between multiple tasks. Multiple tasks present a problem, because it is not possible to be optimal at all tasks simultaneously and hence compromises are necessary. Recent work indicates that trade-offs lead to a simple geometry of phenotypes in the space of traits: phenotypes fall on the Pareto front, which is shaped as a polytope: a line, triangle, tetrahedron etc. The vertices of these polytopes are the optimal phenotypes for a single task. Up to now, work on this Pareto approach has not considered its genetic underpinnings. Here, we address this by asking how the polymorphism structure of a population is affected by evolution under trade-offs. We simulate a multi-task selection scenario, in which the population evolves to the Pareto front: the line segment between two archetypes or the triangle between three archetypes. We find that polymorphisms that become prevalent in the population have pleiotropic phenotypic effects that align with the Pareto front. Similarly, epistatic effects between prevalent polymorphisms are parallel to the front. Alignment with the front occurs also for asexual mating. Alignment is reduced when drift or linkage is strong, and is replaced by a more complex structure in which many perpendicular allele effects cancel out. Aligned polymorphism structure allows mating to produce offspring that stand a good chance of being optimal multi-taskers in at least one of the locales available to the species.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632258, year = {2018}, author = {Kretschmer, S and Harrington, L and Schwille, P}, title = {Reverse and forward engineering of protein pattern formation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632258}, issn = {1471-2970}, abstract = {Living systems employ protein pattern formation to regulate important life processes in space and time. Although pattern-forming protein networks have been identified in various prokaryotes and eukaryotes, their systematic experimental characterization is challenging owing to the complex environment of living cells. In turn, cell-free systems are ideally suited for this goal, as they offer defined molecular environments that can be precisely controlled and manipulated. Towards revealing the molecular basis of protein pattern formation, we outline two complementary approaches: the biochemical reverse engineering of reconstituted networks and the de novo design, or forward engineering, of artificial self-organizing systems. We first illustrate the reverse engineering approach by the example of the Escherichia coli Min system, a model system for protein self-organization based on the reversible and energy-dependent interaction of the ATPase MinD and its activating protein MinE with a lipid membrane. By reconstituting MinE mutants impaired in ATPase stimulation, we demonstrate how large-scale Min protein patterns are modulated by MinE activity and concentration. We then provide a perspective on the de novo design of self-organizing protein networks. Tightly integrated reverse and forward engineering approaches will be key to understanding and engineering the intriguing phenomenon of protein pattern formation.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632257, year = {2018}, author = {Wedlich-Söldner, R and Betz, T}, title = {Self-organization: the fundament of cell biology.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1747}, pages = {}, pmid = {29632257}, issn = {1471-2970}, abstract = {Self-organization refers to the emergence of an overall order in time and space of a given system that results from the collective interactions of its individual components. This concept has been widely recognized as a core principle in pattern formation for multi-component systems of the physical, chemical and biological world. It can be distinguished from self-assembly by the constant input of energy required to maintain order-and self-organization therefore typically occurs in non-equilibrium or dissipative systems. Cells, with their constant energy consumption and myriads of local interactions between distinct proteins, lipids, carbohydrates and nucleic acids, represent the perfect playground for self-organization. It therefore comes as no surprise that many properties and features of self-organized systems, such as spontaneous formation of patterns, nonlinear coupling of reactions, bi-stable switches, waves and oscillations, are found in all aspects of modern cell biology. Ultimately, self-organization lies at the heart of the robustness and adaptability found in cellular and organismal organization, and hence constitutes a fundamental basis for natural selection and evolution.This article is part of the theme issue 'Self-organization in cell biology'.}, } @article {pmid29632214, year = {2018}, author = {Li, H and Zhang, B and Lu, X and Tan, X and Jia, F and Xiao, Y and Cheng, Z and Li, Y and Silva, DO and Schrekker, HS and Zhang, K and Mirkin, CA}, title = {Molecular spherical nucleic acids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4340-4344}, pmid = {29632214}, issn = {1091-6490}, support = {R01 GM121612/GM/NIGMS NIH HHS/United States ; U54 CA199091/CA/NCI NIH HHS/United States ; }, mesh = {*Models, Molecular ; *Nucleic Acid Conformation ; Poly T/*chemistry ; }, abstract = {Herein, we report a class of molecular spherical nucleic acid (SNA) nanostructures. These nano-sized single molecules are synthesized from T8 polyoctahedral silsesquioxane and buckminsterfullerene C60 scaffolds, modified with 8 and 12 pendant DNA strands, respectively. These conjugates have different DNA surface densities and thus exhibit different levels of nuclease resistance, cellular uptake, and gene regulation capabilities; the properties displayed by the C60 SNA conjugate are closer to those of conventional and prototypical gold nanoparticle SNAs. Importantly, the C60 SNA can serve as a single entity (no transfection agent required) antisense agent to efficiently regulate gene expression. The realization of molecularly pure forms of SNAs will open the door for studying the interactions of such structures with ligands and living cells with a much greater degree of control than the conventional polydisperse forms of SNAs.}, } @article {pmid29632213, year = {2018}, author = {Sheikhattar, A and Miran, S and Liu, J and Fritz, JB and Shamma, SA and Kanold, PO and Babadi, B}, title = {Extracting neuronal functional network dynamics via adaptive Granger causality analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3869-E3878}, pmid = {29632213}, issn = {1091-6490}, support = {R01 DC009607/DC/NIDCD NIH HHS/United States ; U01 NS090569/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Auditory Cortex/diagnostic imaging/*physiology ; Calcium/*metabolism ; Calcium Signaling/*physiology ; Mice ; *Models, Neurological ; Nerve Net/diagnostic imaging/*physiology ; }, abstract = {Quantifying the functional relations between the nodes in a network based on local observations is a key challenge in studying complex systems. Most existing time series analysis techniques for this purpose provide static estimates of the network properties, pertain to stationary Gaussian data, or do not take into account the ubiquitous sparsity in the underlying functional networks. When applied to spike recordings from neuronal ensembles undergoing rapid task-dependent dynamics, they thus hinder a precise statistical characterization of the dynamic neuronal functional networks underlying adaptive behavior. We develop a dynamic estimation and inference paradigm for extracting functional neuronal network dynamics in the sense of Granger, by integrating techniques from adaptive filtering, compressed sensing, point process theory, and high-dimensional statistics. We demonstrate the utility of our proposed paradigm through theoretical analysis, algorithm development, and application to synthetic and real data. Application of our techniques to two-photon Ca2+ imaging experiments from the mouse auditory cortex reveals unique features of the functional neuronal network structures underlying spontaneous activity at unprecedented spatiotemporal resolution. Our analysis of simultaneous recordings from the ferret auditory and prefrontal cortical areas suggests evidence for the role of rapid top-down and bottom-up functional dynamics across these areas involved in robust attentive behavior.}, } @article {pmid29632212, year = {2018}, author = {Rider, AT and Henning, GB and Eskew, RT and Stockman, A}, title = {Harmonics added to a flickering light can upset the balance between ON and OFF pathways to produce illusory colors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4081-E4090}, pmid = {29632212}, issn = {1091-6490}, support = {BB/I003444/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M00211X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Aged ; Color Perception/*physiology ; Humans ; *Light ; Male ; Middle Aged ; Optical Illusions/*physiology ; Photoreceptor Cells, Vertebrate/*physiology ; Signal Transduction/*physiology ; Vision, Ocular/*physiology ; }, abstract = {The neural signals generated by the light-sensitive photoreceptors in the human eye are substantially processed and recoded in the retina before being transmitted to the brain via the optic nerve. A key aspect of this recoding is the splitting of the signals within the two major cone-driven visual pathways into distinct ON and OFF branches that transmit information about increases and decreases in the neural signal around its mean level. While this separation is clearly important physiologically, its effect on perception is unclear. We have developed a model of the ON and OFF pathways in early color processing. Using this model as a guide, we can produce imbalances in the ON and OFF pathways by changing the shapes of time-varying stimulus waveforms and thus make reliable and predictable alterations to the perceived average color of the stimulus-although the physical mean of the waveforms does not change. The key components in the model are the early half-wave rectifying synapses that split retinal photoreceptor outputs into the ON and OFF pathways and later sigmoidal nonlinearities in each pathway. The ability to systematically vary the waveforms to change a perceptual quality by changing the balance of signals between the ON and OFF visual pathways provides a powerful psychophysical tool for disentangling and investigating the neural workings of human vision.}, } @article {pmid29632211, year = {2018}, author = {Rajoo, S and Vallotton, P and Onischenko, E and Weis, K}, title = {Stoichiometry and compositional plasticity of the yeast nuclear pore complex revealed by quantitative fluorescence microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3969-E3977}, pmid = {29632211}, issn = {1091-6490}, mesh = {Humans ; Microscopy, Fluorescence/methods ; Nuclear Pore/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {The nuclear pore complex (NPC) is an eightfold symmetrical channel providing selective transport of biomolecules across the nuclear envelope. Each NPC consists of ∼30 different nuclear pore proteins (Nups) all present in multiple copies per NPC. Significant progress has recently been made in the characterization of the vertebrate NPC structure. However, because of the estimated size differences between the vertebrate and yeast NPC, it has been unclear whether the NPC architecture is conserved between species. Here, we have developed a quantitative image analysis pipeline, termed nuclear rim intensity measurement (NuRIM), to precisely determine copy numbers for almost all Nups within native NPCs of budding yeast cells. Our analysis demonstrates that the majority of yeast Nups are present at most in 16 copies per NPC. This reveals a dramatic difference to the stoichiometry determined for the human NPC, suggesting that despite a high degree of individual Nup conservation, the yeast and human NPC architecture is significantly different. Furthermore, using NuRIM, we examined the effects of mutations on NPC stoichiometry. We demonstrate for two paralog pairs of key scaffold Nups, Nup170/Nup157 and Nup192/Nup188, that their altered expression leads to significant changes in the NPC stoichiometry inducing either voids in the NPC structure or substitution of one paralog by the other. Thus, our results not only provide accurate stoichiometry information for the intact yeast NPC but also reveal an intriguing compositional plasticity of the NPC architecture, which may explain how differences in NPC composition could arise in the course of evolution.}, } @article {pmid29632210, year = {2018}, author = {Gerlach, JP and Jordens, I and Tauriello, DVF and van 't Land-Kuper, I and Bugter, JM and Noordstra, I and van der Kooij, J and Low, TY and Pimentel-Muiños, FX and Xanthakis, D and Fenderico, N and Rabouille, C and Heck, AJR and Egan, DA and Maurice, MM}, title = {TMEM59 potentiates Wnt signaling by promoting signalosome formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3996-E4005}, pmid = {29632210}, issn = {1091-6490}, mesh = {Animals ; HEK293 Cells ; Humans ; Low Density Lipoprotein Receptor-Related Protein-6/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Mice ; Multiprotein Complexes/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; Wnt Signaling Pathway/*physiology ; Wnt3A Protein/genetics/*metabolism ; }, abstract = {Wnt/β-catenin signaling controls development and adult tissue homeostasis by regulating cell proliferation and cell fate decisions. Wnt binding to its receptors Frizzled (FZD) and low-density lipoprotein-related 6 (LRP6) at the cell surface initiates a signaling cascade that leads to the transcription of Wnt target genes. Upon Wnt binding, the receptors assemble into large complexes called signalosomes that provide a platform for interactions with downstream effector proteins. The molecular basis of signalosome formation and regulation remains elusive, largely due to the lack of tools to analyze its endogenous components. Here, we use internally tagged Wnt3a proteins to isolate and characterize activated, endogenous Wnt receptor complexes by mass spectrometry-based proteomics. We identify the single-span membrane protein TMEM59 as an interactor of FZD and LRP6 and a positive regulator of Wnt signaling. Mechanistically, TMEM59 promotes the formation of multimeric Wnt-FZD assemblies via intramembrane interactions. Subsequently, these Wnt-FZD-TMEM59 clusters merge with LRP6 to form mature Wnt signalosomes. We conclude that the assembly of multiprotein Wnt signalosomes proceeds along well-ordered steps that involve regulated intramembrane interactions.}, } @article {pmid29632209, year = {2018}, author = {Andreeva, I and Belardinelli, R and Rodnina, MV}, title = {Translation initiation in bacterial polysomes through ribosome loading on a standby site on a highly translated mRNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4411-4416}, pmid = {29632209}, issn = {1091-6490}, mesh = {Bacterial Outer Membrane Proteins/*biosynthesis/genetics ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/*biosynthesis/genetics/metabolism ; Lipoproteins/*biosynthesis/genetics ; Peptide Chain Initiation, Translational/*physiology ; Polyribosomes/genetics/*metabolism ; RNA, Bacterial/genetics/*metabolism ; RNA, Messenger/genetics/*metabolism ; Ribosomal Proteins/genetics/metabolism ; }, abstract = {During translation, consecutive ribosomes load on an mRNA and form a polysome. The first ribosome binds to a single-stranded mRNA region and moves toward the start codon, unwinding potential mRNA structures on the way. In contrast, the following ribosomes can dock at the start codon only when the first ribosome has vacated the initiation site. Here we show that loading of the second ribosome on a natural 38-nt-long 5' untranslated region of lpp mRNA, which codes for the outer membrane lipoprotein from Escherichia coli, takes place before the leading ribosome has moved away from the start codon. The rapid formation of this standby complex depends on the presence of ribosomal proteins S1/S2 in the leading ribosome. The early recruitment of the second ribosome to the standby site before translation by the leading ribosome and the tight coupling between translation elongation by the first ribosome and the accommodation of the second ribosome can contribute to high translational efficiency of the lpp mRNA.}, } @article {pmid29632208, year = {2018}, author = {Majee, M and Kumar, S and Kathare, PK and Wu, S and Gingerich, D and Nayak, NR and Salaita, L and Dinkins, R and Martin, K and Goodin, M and Dirk, LMA and Lloyd, TD and Zhu, L and Chappell, J and Hunt, AG and Vierstra, R and Huq, E and Downie, AB}, title = {KELCH F-BOX protein positively influences Arabidopsis seed germination by targeting PHYTOCHROME-INTERACTING FACTOR1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4120-E4129}, pmid = {29632208}, issn = {1091-6490}, support = {R01 GM114297/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Germination/*physiology ; Kelch Repeat ; Seeds/genetics/*metabolism ; }, abstract = {Seeds employ sensory systems that assess various environmental cues over time to maximize the successful transition from embryo to seedling. Here we show that the Arabidopsis F-BOX protein COLD TEMPERATURE-GERMINATING (CTG)-10, identified by activation tagging, is a positive regulator of this process. When overexpressed (OE), CTG10 hastens aspects of seed germination. CTG10 is expressed predominantly in the hypocotyl, and the protein is localized to the nucleus. CTG10 interacts with PHYTOCHROME-INTERACTING FACTOR 1 (PIF1) and helps regulate its abundance in plantaCTG10-OE accelerates the loss of PIF1 in light, increasing germination efficiency, while PIF1-OE lines fail to complete germination in darkness, which is reversed by concurrent CTG10-OE Double-mutant (pif1 ctg10) lines demonstrated that PIF1 is epistatic to CTG10. Both CTG10 and PIF1 amounts decline during seed germination in the light but reaccumulate in the dark. PIF1 in turn down-regulates CTG10 transcription, suggesting a feedback loop of CTG10/PIF1 control. The genetic, physiological, and biochemical evidence, when taken together, leads us to propose that PIF1 and CTG10 coexist, and even accumulate, in the nucleus in darkness, but that, following illumination, CTG10 assists in reducing PIF1 amounts, thus promoting the completion of seed germination and subsequent seedling development.}, } @article {pmid29632207, year = {2018}, author = {Steurer, B and Janssens, RC and Geverts, B and Geijer, ME and Wienholz, F and Theil, AF and Chang, J and Dealy, S and Pothof, J and van Cappellen, WA and Houtsmuller, AB and Marteijn, JA}, title = {Live-cell analysis of endogenous GFP-RPB1 uncovers rapid turnover of initiating and promoter-paused RNA Polymerase II.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4368-E4376}, pmid = {29632207}, issn = {1091-6490}, mesh = {Cell Line, Transformed ; Gene Knock-In Techniques ; Green Fluorescent Proteins/genetics/metabolism ; Humans ; Promoter Regions, Genetic/*physiology ; RNA Polymerase II/genetics/*metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Transcription, Genetic/*physiology ; }, abstract = {Initiation and promoter-proximal pausing are key regulatory steps of RNA Polymerase II (Pol II) transcription. To study the in vivo dynamics of endogenous Pol II during these steps, we generated fully functional GFP-RPB1 knockin cells. GFP-RPB1 photobleaching combined with computational modeling revealed four kinetically distinct Pol II fractions and showed that on average 7% of Pol II are freely diffusing, while 10% are chromatin-bound for 2.4 seconds during initiation, and 23% are promoter-paused for only 42 seconds. This unexpectedly high turnover of Pol II at promoters is most likely caused by premature termination of initiating and promoter-paused Pol II and is in sharp contrast to the 23 minutes that elongating Pol II resides on chromatin. Our live-cell-imaging approach provides insights into Pol II dynamics and suggests that the continuous release and reinitiation of promoter-bound Pol II is an important component of transcriptional regulation.}, } @article {pmid29632206, year = {2018}, author = {Zou, J and Ma, W and Li, J and Littlejohn, R and Zhou, H and Kim, IM and Fulton, DJR and Chen, W and Weintraub, NL and Zhou, J and Su, H}, title = {Neddylation mediates ventricular chamber maturation through repression of Hippo signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4101-E4110}, pmid = {29632206}, issn = {1091-6490}, support = {R01 HL126949/HL/NHLBI NIH HHS/United States ; F31 HL139079/HL/NHLBI NIH HHS/United States ; R01 HL124248/HL/NHLBI NIH HHS/United States ; R01 HL125926/HL/NHLBI NIH HHS/United States ; R01 HL109605/HL/NHLBI NIH HHS/United States ; R01 HL132164/HL/NHLBI NIH HHS/United States ; R01 HL124251/HL/NHLBI NIH HHS/United States ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Animals ; Cullin Proteins/genetics/metabolism ; Heart Ventricles/*metabolism/pathology ; Mice ; Mice, Knockout ; Myocardium/*metabolism/pathology ; Myocytes, Cardiac/*metabolism/pathology ; NEDD8 Protein/genetics/*metabolism ; Phosphoproteins/genetics/metabolism ; *Protein Processing, Post-Translational ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; *Signal Transduction ; Tumor Suppressor Proteins/genetics/metabolism ; }, abstract = {During development, ventricular chamber maturation is a crucial step in the formation of a functionally competent postnatal heart. Defects in this process can lead to left ventricular noncompaction cardiomyopathy and heart failure. However, molecular mechanisms underlying ventricular chamber development remain incompletely understood. Neddylation is a posttranslational modification that attaches ubiquitin-like protein NEDD8 to protein targets via NEDD8-specific E1-E2-E3 enzymes. Here, we report that neddylation is temporally regulated in the heart and plays a key role in cardiac development. Cardiomyocyte-specific knockout of NAE1, a subunit of the E1 neddylation activating enzyme, significantly decreased neddylated proteins in the heart. Mice lacking NAE1 developed myocardial hypoplasia, ventricular noncompaction, and heart failure at late gestation, which led to perinatal lethality. NAE1 deletion resulted in dysregulation of cell cycle-regulatory genes and blockade of cardiomyocyte proliferation in vivo and in vitro, which was accompanied by the accumulation of the Hippo kinases Mst1 and LATS1/2 and the inactivation of the YAP pathway. Furthermore, reactivation of YAP signaling in NAE1-inactivated cardiomyocytes restored cell proliferation, and YAP-deficient hearts displayed a noncompaction phenotype, supporting an important role of Hippo-YAP signaling in NAE1-depleted hearts. Mechanistically, we found that neddylation regulates Mst1 and LATS2 degradation and that Cullin 7, a NEDD8 substrate, acts as the ubiquitin ligase of Mst1 to enable YAP signaling and cardiomyocyte proliferation. Together, these findings demonstrate a role for neddylation in heart development and, more specifically, in the maturation of ventricular chambers and also identify the NEDD8 substrate Cullin 7 as a regulator of Hippo-YAP signaling.}, } @article {pmid29632205, year = {2018}, author = {Dundas, K and Shears, MJ and Sun, Y and Hopp, CS and Crosnier, C and Metcalf, T and Girling, G and Sinnis, P and Billker, O and Wright, GJ}, title = {Alpha-v-containing integrins are host receptors for the Plasmodium falciparum sporozoite surface protein, TRAP.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4477-4482}, pmid = {29632205}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 AI056840/AI/NIAID NIH HHS/United States ; R01 AI132359/AI/NIAID NIH HHS/United States ; 206194//Wellcome Trust/United Kingdom ; MR/J004111/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; HEK293 Cells ; Humans ; Integrin alphaVbeta3/genetics/*metabolism ; Mice ; Mice, Knockout ; *Models, Biological ; Plasmodium falciparum/genetics/*metabolism/pathogenicity ; Protozoan Proteins/genetics/*metabolism ; Sporozoites/genetics/*metabolism ; }, abstract = {Malaria-causing Plasmodium sporozoites are deposited in the dermis by the bite of an infected mosquito and move by gliding motility to the liver where they invade and develop within host hepatocytes. Although extracellular interactions between Plasmodium sporozoite ligands and host receptors provide important guidance cues for productive infection and are good vaccine targets, these interactions remain largely uncharacterized. Thrombospondin-related anonymous protein (TRAP) is a parasite cell surface ligand that is essential for both gliding motility and invasion because it couples the extracellular binding of host receptors to the parasite cytoplasmic actinomyosin motor; however, the molecular nature of the host TRAP receptors is poorly defined. Here, we use a systematic extracellular protein interaction screening approach to identify the integrin αvβ3 as a directly interacting host receptor for Plasmodium falciparum TRAP. Biochemical characterization of the interaction suggests a two-site binding model, requiring contributions from both the von Willebrand factor A domain and the RGD motif of TRAP for integrin binding. We show that TRAP binding to cells is promoted in the presence of integrin-activating proadhesive Mn2+ ions, and that cells genetically targeted so that they lack cell surface expression of the integrin αv-subunit are no longer able to bind TRAP. P. falciparum sporozoites moved with greater speed in the dermis of Itgb3-deficient mice, suggesting that the interaction has a role in sporozoite migration. The identification of the integrin αvβ3 as the host receptor for TRAP provides an important demonstration of a sporozoite surface ligand that directly interacts with host receptors.}, } @article {pmid29632204, year = {2018}, author = {Yang, D and Li, Y and Liu, X and Cao, Y and Gao, Y and Shen, YR and Liu, WT}, title = {Facet-specific interaction between methanol and TiO2 probed by sum-frequency vibrational spectroscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3888-E3894}, pmid = {29632204}, issn = {1091-6490}, abstract = {The facet-specific interaction between molecules and crystalline catalysts, such as titanium dioxides (TiO2), has attracted much attention due to possible facet-dependent reactivity. Using surface-sensitive sum-frequency vibrational spectroscopy, we have studied how methanol interacts with different common facets of crystalline TiO2, including rutile(110), (001), (100), and anatase(101), under ambient temperature and pressure. We found that methanol adsorbs predominantly in the molecular form on all of the four surfaces, while spontaneous dissociation into methoxy occurs preferentially when these surfaces become defective. Extraction of Fermi resonance coupling between stretch and bending modes of the methyl group in analyzing adsorbed methanol spectra allows determination of the methanol adsorption isotherm. The isotherms obtained for the four surfaces are nearly the same, yielding two adsorbed Gibbs free energies associated with two different adsorption configurations singled out by ab initio calculations. They are (i) ∼-20 kJ/mol for methanol with its oxygen attached to a low-coordinated surface titanium, and (ii) ∼-5 kJ/mol for methanol hydrogen-bonded to a surface oxygen and a neighboring methanol molecule. Despite similar adsorption energetics, the Fermi resonance coupling strength for adsorbed methanol appears to depend sensitively on the surface facet and coverage.}, } @article {pmid29632203, year = {2018}, author = {Muse, ED and Yu, S and Edillor, CR and Tao, J and Spann, NJ and Troutman, TD and Seidman, JS and Henke, A and Roland, JT and Ozeki, KA and Thompson, BM and McDonald, JG and Bahadorani, J and Tsimikas, S and Grossman, TR and Tremblay, MS and Glass, CK}, title = {Cell-specific discrimination of desmosterol and desmosterol mimetics confers selective regulation of LXR and SREBP in macrophages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {20}, pages = {E4680-E4689}, pmid = {29632203}, issn = {1091-6490}, support = {P01 HL088093/HL/NHLBI NIH HHS/United States ; P01 HL020948/HL/NHLBI NIH HHS/United States ; UL1 TR001114/TR/NCATS NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; T32 DK007541/DK/NIDDK NIH HHS/United States ; P50 GM085764/GM/NIGMS NIH HHS/United States ; T32 CA009523/CA/NCI NIH HHS/United States ; KL2 TR001112/TR/NCATS NIH HHS/United States ; T32 GM007198/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biomimetics ; Desmosterol/*pharmacology ; Gene Expression Regulation/*drug effects ; Hep G2 Cells ; Hepatocytes/cytology/drug effects/*metabolism ; Humans ; Liver X Receptors/genetics/*metabolism ; Macrophages/cytology/drug effects/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; Sterol Regulatory Element Binding Protein 1/genetics/*metabolism ; }, abstract = {Activation of liver X receptors (LXRs) with synthetic agonists promotes reverse cholesterol transport and protects against atherosclerosis in mouse models. Most synthetic LXR agonists also cause marked hypertriglyceridemia by inducing the expression of sterol regulatory element-binding protein (SREBP)1c and downstream genes that drive fatty acid biosynthesis. Recent studies demonstrated that desmosterol, an intermediate in the cholesterol biosynthetic pathway that suppresses SREBP processing by binding to SCAP, also binds and activates LXRs and is the most abundant LXR ligand in macrophage foam cells. Here we explore the potential of increasing endogenous desmosterol production or mimicking its activity as a means of inducing LXR activity while simultaneously suppressing SREBP1c-induced hypertriglyceridemia. Unexpectedly, while desmosterol strongly activated LXR target genes and suppressed SREBP pathways in mouse and human macrophages, it had almost no activity in mouse or human hepatocytes in vitro. We further demonstrate that sterol-based selective modulators of LXRs have biochemical and transcriptional properties predicted of desmosterol mimetics and selectively regulate LXR function in macrophages in vitro and in vivo. These studies thereby reveal cell-specific discrimination of endogenous and synthetic regulators of LXRs and SREBPs, providing a molecular basis for dissociation of LXR functions in macrophages from those in the liver that lead to hypertriglyceridemia.}, } @article {pmid29632202, year = {2018}, author = {Rubenstein, PA and Wen, KK}, title = {NATure of actin amino-terminal acetylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4314-4316}, pmid = {29632202}, issn = {1091-6490}, mesh = {Acetylation ; Actins/*genetics ; *Amino Acid Sequence ; Protein Processing, Post-Translational ; }, } @article {pmid29632201, year = {2018}, author = {Kusminski, CM and Scherer, PE}, title = {New zoning laws enforced by glucagon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4308-4310}, pmid = {29632201}, issn = {1091-6490}, support = {P01 AG051459/AG/NIA NIH HHS/United States ; P01 DK088761/DK/NIDDK NIH HHS/United States ; R01 DK055758/DK/NIDDK NIH HHS/United States ; R01 DK099110/DK/NIDDK NIH HHS/United States ; }, mesh = {*City Planning ; Conservation of Natural Resources ; *Glucagon ; }, } @article {pmid29632200, year = {2018}, author = {Wang, L and Chauliac, D and Rhee, MS and Panneerselvam, A and Ingram, LO and Shanmugam, KT}, title = {Fermentation of dihydroxyacetone by engineered Escherichia coli and Klebsiella variicola to products.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4381-4386}, pmid = {29632200}, issn = {1091-6490}, mesh = {Dihydroxyacetone/*metabolism ; Escherichia coli/genetics/*growth & development ; Fermentation/physiology ; Glucose/metabolism ; Klebsiella/genetics/*growth & development ; Lactic Acid/*biosynthesis ; *Metabolic Engineering ; Microorganisms, Genetically-Modified/*growth & development/metabolism ; }, abstract = {Methane can be converted to triose dihydroxyacetone (DHA) by chemical processes with formaldehyde as an intermediate. Carbon dioxide, a by-product of various industries including ethanol/butanol biorefineries, can also be converted to formaldehyde and then to DHA. DHA, upon entry into a cell and phosphorylation to DHA-3-phosphate, enters the glycolytic pathway and can be fermented to any one of several products. However, DHA is inhibitory to microbes due to its chemical interaction with cellular components. Fermentation of DHA to d-lactate by Escherichia coli strain TG113 was inefficient, and growth was inhibited by 30 g⋅L-1 DHA. An ATP-dependent DHA kinase from Klebsiella oxytoca (pDC117d) permitted growth of strain TG113 in a medium with 30 g⋅L-1 DHA, and in a fed-batch fermentation the d-lactate titer of TG113(pDC117d) was 580 ± 21 mM at a yield of 0.92 g⋅g-1 DHA fermented. Klebsiella variicola strain LW225, with a higher glucose flux than E. coli, produced 811 ± 26 mM d-lactic acid at an average volumetric productivity of 2.0 g-1⋅L-1⋅h-1 Fermentation of DHA required a balance between transport of the triose and utilization by the microorganism. Using other engineered E. coli strains, we also fermented DHA to succinic acid and ethanol, demonstrating the potential of converting CH4 and CO2 to value-added chemicals and fuels by a combination of chemical/biological processes.}, } @article {pmid29632199, year = {2018}, author = {Armbruster, CR and Parsek, MR}, title = {New insight into the early stages of biofilm formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4317-4319}, pmid = {29632199}, issn = {1091-6490}, support = {R01 AI077628/AI/NIAID NIH HHS/United States ; }, mesh = {*Biofilms ; }, } @article {pmid29632198, year = {2018}, author = {Nilges, T}, title = {Expressway to partially oxidized phosphorene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4311-4313}, pmid = {29632198}, issn = {1091-6490}, mesh = {Adsorption ; China ; *Government Regulation ; Incidence ; *Oxidation-Reduction ; Wounds and Injuries ; }, } @article {pmid29632197, year = {2018}, author = {Dannberg, J and Gassmöller, R}, title = {Chemical trends in ocean islands explained by plume-slab interaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4351-4356}, pmid = {29632197}, issn = {1091-6490}, abstract = {Earth's surface shows many features, of which the genesis can be understood only through their connection with processes in Earth's deep interior. Recent studies indicate that spatial geochemical patterns at oceanic islands correspond to structures in the lowermost mantle inferred from seismic tomographic models. This suggests that hot, buoyant upwellings can carry chemical heterogeneities from the deep lower mantle toward the surface, providing a window to the composition of the lowermost mantle. The exact nature of this link between surface and deep Earth remains debated and poorly understood. Using computational models, we show that subducted slabs interacting with dense thermochemical piles can trigger the ascent of hot plumes that inherit chemical gradients present in the lowermost mantle. We identify two key factors controlling this process: (i) If slabs induce strong lower-mantle flow toward the edges of these piles where plumes rise, the pile-facing side of the plume preferentially samples material originating from the pile, and bilaterally asymmetric chemical zoning develops. (ii) The composition of the melt produced reflects this bilateral zoning if the overlying plate moves roughly perpendicular to the chemical gradient in the plume conduit. Our results explain some of the observed geochemical trends of oceanic islands and provide insights into how these trends may originate.}, } @article {pmid29632196, year = {2018}, author = {Peranzoni, E and Lemoine, J and Vimeux, L and Feuillet, V and Barrin, S and Kantari-Mimoun, C and Bercovici, N and Guérin, M and Biton, J and Ouakrim, H and Régnier, F and Lupo, A and Alifano, M and Damotte, D and Donnadieu, E}, title = {Macrophages impede CD8 T cells from reaching tumor cells and limit the efficacy of anti-PD-1 treatment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4041-E4050}, pmid = {29632196}, issn = {1091-6490}, mesh = {Aminopyridines/pharmacology ; Animals ; CD8-Positive T-Lymphocytes/*immunology/pathology ; Carcinoma, Squamous Cell/*drug therapy/*immunology/pathology ; Follow-Up Studies ; Macrophages/*immunology/pathology ; Mice ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors/immunology ; Pyrroles/pharmacology ; Receptor, Macrophage Colony-Stimulating Factor/antagonists & inhibitors/immunology ; Retrospective Studies ; Xenograft Model Antitumor Assays ; }, abstract = {In a large proportion of cancer patients, CD8 T cells are excluded from the vicinity of cancer cells. The inability of CD8 T cells to reach tumor cells is considered an important mechanism of resistance to cancer immunotherapy. We show that, in human lung squamous-cell carcinomas, exclusion of CD8 T cells from tumor islets is correlated with a poor clinical outcome and with a low lymphocyte motility, as assessed by dynamic imaging on fresh tumor slices. In the tumor stroma, macrophages mediate lymphocyte trapping by forming long-lasting interactions with CD8 T cells. Using a mouse tumor model with well-defined stromal and tumor cell areas, macrophages were depleted with PLX3397, an inhibitor of colony-stimulating factor-1 receptor (CSF-1R). Our results reveal that a CSF-1R blockade enhances CD8 T cell migration and infiltration into tumor islets. Although this treatment alone has minor effects on tumor growth, its combination with anti-PD-1 therapy further increases the accumulation of CD8 T cells in close contact with malignant cells and delays tumor progression. These data suggest that the reduction of macrophage-mediated T cell exclusion increases tumor surveillance by CD8 T cells and renders tumors more responsive to anti-PD-1 treatment.}, } @article {pmid29632195, year = {2018}, author = {Zerubavel, N and Hoffman, MA and Reich, A and Ochsner, KN and Bearman, P}, title = {Neural precursors of future liking and affective reciprocity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4375-4380}, pmid = {29632195}, issn = {1091-6490}, mesh = {Adult ; Brain/*diagnostic imaging/*physiology ; Emotions/*physiology ; Female ; Humans ; *Magnetic Resonance Imaging ; Male ; Neurons/*physiology ; *Social Behavior ; }, abstract = {Why do certain group members end up liking each other more than others? How does affective reciprocity arise in human groups? The prediction of interpersonal sentiment has been a long-standing pursuit in the social sciences. We combined fMRI and longitudinal social network data to test whether newly acquainted group members' reward-related neural responses to images of one another's faces predict their future interpersonal sentiment, even many months later. Specifically, we analyze associations between relationship-specific valuation activity and relationship-specific future liking. We found that one's own future (T2) liking of a particular group member is predicted jointly by actor's initial (T1) neural valuation of partner and by that partner's initial (T1) neural valuation of actor. These actor and partner effects exhibited equivalent predictive strength and were robust when statistically controlling for each other, both individuals' initial liking, and other potential drivers of liking. Behavioral findings indicated that liking was initially unreciprocated at T1 yet became strongly reciprocated by T2. The emergence of affective reciprocity was partly explained by the reciprocal pathways linking dyad members' T1 neural data both to their own and to each other's T2 liking outcomes. These findings elucidate interpersonal brain mechanisms that define how we ultimately end up liking particular interaction partners, how group members' initially idiosyncratic sentiments become reciprocated, and more broadly, how dyads evolve. This study advances a flexible framework for researching the neural foundations of interpersonal sentiments and social relations that-conceptually, methodologically, and statistically-emphasizes group members' neural interdependence.}, } @article {pmid29632194, year = {2018}, author = {Wu, Q and Tian, Y and Zhang, J and Tong, X and Huang, H and Li, S and Zhao, H and Tang, Y and Yuan, C and Wang, K and Fang, Z and Gao, L and Hu, X and Li, F and Qin, Z and Yao, S and Chen, T and Chen, H and Zhang, G and Liu, W and Sun, Y and Chen, L and Wong, KK and Ge, K and Chen, L and Ji, H}, title = {In vivo CRISPR screening unveils histone demethylase UTX as an important epigenetic regulator in lung tumorigenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3978-E3986}, pmid = {29632194}, issn = {1091-6490}, mesh = {Animals ; *CRISPR-Cas Systems ; Cell Transformation, Neoplastic/genetics/*metabolism/pathology ; *Epigenesis, Genetic ; *Gene Expression Regulation, Neoplastic ; Histone Demethylases/genetics/*metabolism ; Humans ; Lung Neoplasms/genetics/*metabolism/pathology ; Mice ; Mice, Knockout ; Neoplasms, Experimental/genetics/*metabolism/pathology ; Proto-Oncogene Proteins p21(ras)/genetics/metabolism ; Tumor Suppressor Proteins/genetics/metabolism ; }, abstract = {Lung cancer is the leading cause of cancer-related death worldwide. Inactivation of tumor suppressor genes (TSGs) promotes lung cancer malignant progression. Here, we take advantage of the clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9-mediated somatic gene knockout in a KrasG12D/+ mouse model to identify bona fide TSGs. From individual knockout of 55 potential TSGs, we identify five genes, including Utx, Ptip, Acp5, Acacb, and Clu, whose knockout significantly promotes lung tumorigenesis. These candidate genes are frequently down-regulated in human lung cancer specimens and significantly associated with survival in patients with lung cancer. Through crossing the conditional Utx knockout allele to the KrasG12D/+ mouse model, we further find that Utx deletion dramatically promotes lung cancer progression. The tumor-promotive effect of Utx knockout in vivo is mainly mediated through an increase of the EZH2 level, which up-regulates the H3K27me3 level. Moreover, the Utx-knockout lung tumors are preferentially sensitive to EZH2 inhibitor treatment. Collectively, our study provides a systematic screening of TSGs in vivo and identifies UTX as an important epigenetic regulator in lung tumorigenesis.}, } @article {pmid29632193, year = {2018}, author = {Ranger, CM and Biedermann, PHW and Phuntumart, V and Beligala, GU and Ghosh, S and Palmquist, DE and Mueller, R and Barnett, J and Schultz, PB and Reding, ME and Benz, JP}, title = {Symbiont selection via alcohol benefits fungus farming by ambrosia beetles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4447-4452}, pmid = {29632193}, issn = {1091-6490}, mesh = {Animals ; Aspergillus/*physiology ; Coleoptera/*microbiology ; Ethanol/metabolism/*pharmacology ; Penicillium/*physiology ; Symbiosis/*drug effects/physiology ; }, abstract = {Animal-microbe mutualisms are typically maintained by vertical symbiont transmission or partner choice. A third mechanism, screening of high-quality symbionts, has been predicted in theory, but empirical examples are rare. Here we demonstrate that ambrosia beetles rely on ethanol within host trees for promoting gardens of their fungal symbiont and producing offspring. Ethanol has long been known as the main attractant for many of these fungus-farming beetles as they select host trees in which they excavate tunnels and cultivate fungal gardens. More than 300 attacks by Xylosandrus germanus and other species were triggered by baiting trees with ethanol lures, but none of the foundresses established fungal gardens or produced broods unless tree tissues contained in vivo ethanol resulting from irrigation with ethanol solutions. More X. germanus brood were also produced in a rearing substrate containing ethanol. These benefits are a result of increased food supply via the positive effects of ethanol on food-fungus biomass. Selected Ambrosiella and Raffaelea fungal isolates from ethanol-responsive ambrosia beetles profited directly and indirectly by (i) a higher biomass on medium containing ethanol, (ii) strong alcohol dehydrogenase enzymatic activity, and (iii) a competitive advantage over weedy fungal garden competitors (Aspergillus, Penicillium) that are inhibited by ethanol. As ambrosia fungi both detoxify and produce ethanol, they may maintain the selectivity of their alcohol-rich habitat for their own purpose and that of other ethanol-resistant/producing microbes. This resembles biological screening of beneficial symbionts and a potentially widespread, unstudied benefit of alcohol-producing symbionts (e.g., yeasts) in other microbial symbioses.}, } @article {pmid29632192, year = {2018}, author = {Hu, H and Nemecz, Á and Van Renterghem, C and Fourati, Z and Sauguet, L and Corringer, PJ and Delarue, M}, title = {Crystal structures of a pentameric ion channel gated by alkaline pH show a widely open pore and identify a cavity for modulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3959-E3968}, pmid = {29632192}, issn = {1091-6490}, mesh = {Allosteric Regulation ; Bacterial Proteins/antagonists & inhibitors/*chemistry ; Crystallography, X-Ray ; Gammaproteobacteria/*enzymology ; Hydrogen-Ion Concentration ; Ligand-Gated Ion Channels/antagonists & inhibitors/*chemistry ; Quaternary Ammonium Compounds/chemistry ; }, abstract = {Pentameric ligand-gated ion channels (pLGICs) constitute a widespread class of ion channels, present in archaea, bacteria, and eukaryotes. Upon binding of their agonists in the extracellular domain, the transmembrane pore opens, allowing ions to go through, via a gating mechanism that can be modulated by a number of drugs. Even though high-resolution structural information on pLGICs has increased in a spectacular way in recent years, both in bacterial and in eukaryotic systems, the structure of the open channel conformation of some intensively studied receptors whose structures are known in a nonactive (closed) form, such as Erwinia chrysanthemi pLGIC (ELIC), is still lacking. Here we describe a gammaproteobacterial pLGIC from an endo-symbiont of Tevnia jerichonana (sTeLIC), whose sequence is closely related to the pLGIC from ELIC with 28% identity. We provide an X-ray crystallographic structure at 2.3 Å in an active conformation, where the pore is found to be more open than any current conformation found for pLGICs. In addition, two charged restriction rings are present in the vestibule. Functional characterization shows sTeLIC to be a cationic channel activated at alkaline pH. It is inhibited by divalent cations, but not by quaternary ammonium ions, such as tetramethylammonium. Additionally, we found that sTeLIC is allosterically potentiated by aromatic amino acids Phe and Trp, as well as their derivatives, such as 4-bromo-cinnamate, whose cocrystal structure reveals a vestibular binding site equivalent to, but more deeply buried than, the one already described for benzodiazepines in ELIC.}, } @article {pmid29632191, year = {2018}, author = {}, title = {Correction for Kobayashi et al., B and T lymphocyte attenuator inhibits LPS-induced endotoxic shock by suppressing Toll-like receptor 4 signaling in innate immune cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4141}, doi = {10.1073/pnas.1805035115}, pmid = {29632191}, issn = {1091-6490}, } @article {pmid29632190, year = {2018}, author = {Dahotre, SN and Chang, YM and Wieland, A and Stammen, SR and Kwong, GA}, title = {Individually addressable and dynamic DNA gates for multiplexed cell sorting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4357-4362}, pmid = {29632190}, issn = {1091-6490}, support = {DP2 HD091793/HD/NICHD NIH HHS/United States ; T32 GM008169/GM/NIGMS NIH HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; *CD4-Positive T-Lymphocytes/immunology/pathology ; *CD8-Positive T-Lymphocytes/immunology/pathology ; *Cell Proliferation ; Flow Cytometry/*methods ; *Lymphocytic Choriomeningitis/immunology/pathology ; Lymphocytic choriomeningitis virus/*immunology ; Mice ; }, abstract = {The ability to analyze and isolate cells based on the expression of specific surface markers has increased our understanding of cell biology and produced numerous applications for biomedicine. However, established cell-sorting platforms rely on labels that are limited in number due to biophysical constraints, such as overlapping emission spectra of fluorophores in FACS. Here, we establish a framework built on a system of orthogonal and extensible DNA gates for multiplexed cell sorting. These DNA gates label target cell populations by antibodies to allow magnetic bead isolation en masse and then selectively unlock by strand displacement to sort cells. We show that DNA gated sorting (DGS) is triggered to completion within minutes on the surface of cells and achieves target cell purity, viability, and yield equivalent to that of commercial magnetic sorting kits. We demonstrate multiplexed sorting of three distinct immune cell populations (CD8+, CD4+, and CD19+) from mouse splenocytes to high purity and show that recovered CD8+ T cells retain proliferative potential and target cell-killing activity. To broaden the utility of this platform, we implement a double positive sorting scheme using DNA gates on peptide-MHC tetramers to isolate antigen-specific CD8+ T cells from mice infected with lymphocytic choriomeningitis virus (LCMV). DGS can potentially be expanded with fewer biophysical constraints to large families of DNA gates for applications that require analysis of complex cell populations, such as host immune responses to disease.}, } @article {pmid29632189, year = {2018}, author = {Shang, W and Jiang, Y and Boettcher, M and Ding, K and Mollenauer, M and Liu, Z and Wen, X and Liu, C and Hao, P and Zhao, S and McManus, MT and Wei, L and Weiss, A and Wang, H}, title = {Genome-wide CRISPR screen identifies FAM49B as a key regulator of actin dynamics and T cell activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4051-E4060}, pmid = {29632189}, issn = {1091-6490}, support = {R37 AI114575/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Actins/genetics ; Antigens, CD/genetics/immunology ; Antigens, Differentiation, T-Lymphocyte/genetics/immunology ; CRISPR-Cas Systems ; Cytoskeleton/genetics/immunology ; Genome-Wide Association Study ; Humans ; Jurkat Cells ; Lectins, C-Type/genetics/immunology ; *Lymphocyte Activation ; Neoplasm Proteins/genetics/*immunology ; Proto-Oncogene Proteins c-akt/genetics/immunology ; T-Lymphocytes/cytology/*immunology ; }, abstract = {Despite decades of research, mechanisms controlling T cell activation remain only partially understood, which hampers T cell-based immune cancer therapies. Here, we performed a genome-wide CRISPR screen to search for genes that regulate T cell activation. Our screen confirmed many of the known regulators in proximal T cell receptor signaling and, importantly, also uncovered a previously uncharacterized regulator, FAM49B (family with sequence similarity 49 member B). FAM49B deficiency led to hyperactivation of Jurkat T cells following T cell receptor stimulation, as indicated by enhancement of CD69 induction, PAK phosphorylation, and actin assembly. FAM49B directly interacted with the active form of the small GTPase Rac, and genetic disruption of the FAM49B-Rac interaction compromised FAM49B function. Thus, FAM49B inhibits T cell activation by repressing Rac activity and modulating cytoskeleton reorganization.}, } @article {pmid29632188, year = {2018}, author = {de la Fuente, C and Ávila-Arcos, MC and Galimany, J and Carpenter, ML and Homburger, JR and Blanco, A and Contreras, P and Cruz Dávalos, D and Reyes, O and San Roman, M and Moreno-Estrada, A and Campos, PF and Eng, C and Huntsman, S and Burchard, EG and Malaspinas, AS and Bustamante, CD and Willerslev, E and Llop, E and Verdugo, RA and Moraga, M}, title = {Genomic insights into the origin and diversification of late maritime hunter-gatherers from the Chilean Patagonia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4006-E4012}, pmid = {29632188}, issn = {1091-6490}, support = {T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Chile ; Female ; *Genetic Variation ; *Genome, Human ; History, Ancient ; Humans ; Indians, South American/*genetics/history ; Male ; }, abstract = {Patagonia was the last region of the Americas reached by humans who entered the continent from Siberia ∼15,000-20,000 y ago. Despite recent genomic approaches to reconstruct the continental evolutionary history, regional characterization of ancient and modern genomes remains understudied. Exploring the genomic diversity within Patagonia is not just a valuable strategy to gain a better understanding of the history and diversification of human populations in the southernmost tip of the Americas, but it would also improve the representation of Native American diversity in global databases of human variation. Here, we present genome data from four modern populations from Central Southern Chile and Patagonia (n = 61) and four ancient maritime individuals from Patagonia (∼1,000 y old). Both the modern and ancient individuals studied in this work have a greater genetic affinity with other modern Native Americans than to any non-American population, showing within South America a clear structure between major geographical regions. Native Patagonian Kawéskar and Yámana showed the highest genetic affinity with the ancient individuals, indicating genetic continuity in the region during the past 1,000 y before present, together with an important agreement between the ethnic affiliation and historical distribution of both groups. Lastly, the ancient maritime individuals were genetically equidistant to a ∼200-y-old terrestrial hunter-gatherer from Tierra del Fuego, which supports a model with an initial separation of a common ancestral group to both maritime populations from a terrestrial population, with a later diversification of the maritime groups.}, } @article {pmid29632187, year = {2018}, author = {Shirhatti, V and Ray, S}, title = {Long-wavelength (reddish) hues induce unusually large gamma oscillations in the primate primary visual cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4489-4494}, pmid = {29632187}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 500145-Z-09-Z//Wellcome Trust-DBT India Alliance/India ; }, mesh = {Animals ; Female ; Gamma Rhythm/*physiology ; Humans ; Macaca radiata ; Visual Cortex/*diagnostic imaging/*physiology ; }, abstract = {Gamma oscillations (∼30-80 Hz) are a prominent signature of electrophysiological signals, with a purported role in natural vision. Previous studies in the primary visual cortex (area V1) have shown that achromatic gratings or gabor stimuli generate salient gamma oscillations, whose strength and frequency depend on stimulus properties such as their size, contrast, and orientation. Surprisingly, although natural images are rarely achromatic, the effect of chromatic input on gamma has not been thoroughly investigated. Recording from primate V1, we show that gamma oscillations of extremely high magnitude (peak increase of ∼300-fold in some cases), far exceeding the gamma generated by optimally tuned achromatic gratings, are induced in the local field potentials by full-field color stimuli of different hues. Furthermore, gamma oscillations are sensitive to the hue of the chromatic input, with the strongest oscillations for long-wavelength (reddish) hues and another, smaller gamma response peak for hues in the short-wavelength (bluish) range, which lie approximately on the two cardinal chromatic response axes of the upstream lateral geniculate nucleus neurons. These oscillations depended critically on the purity of the hue, decreasing with hue desaturation, but remained robust for pure hue stimuli even at reduced luminance. Importantly, the magnitude of gamma oscillations was highly correlated with positive L-M cone contrast produced by the stimuli, suggesting that gamma could be a marker of the specific mechanisms underlying this computation. These findings provide insights into the generation of gamma oscillations, as well as the processing of color along the visual pathway.}, } @article {pmid29632186, year = {2018}, author = {Mao, CP and Peng, S and Yang, A and He, L and Tsai, YC and Hung, CF and Wu, TC}, title = {Programmed self-assembly of peptide-major histocompatibility complex for antigen-specific immune modulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4032-E4040}, pmid = {29632186}, issn = {1091-6490}, support = {R21 CA194896/CA/NCI NIH HHS/United States ; R01 CA114425/CA/NCI NIH HHS/United States ; T32 GM007309/GM/NIGMS NIH HHS/United States ; P50 CA098252/CA/NCI NIH HHS/United States ; R21 AI109259/AI/NIAID NIH HHS/United States ; P50 CA096784/CA/NCI NIH HHS/United States ; F30 CA177221/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Annexin A5/genetics/*immunology ; Female ; Histocompatibility Antigens/genetics/*immunology ; Mice ; Mice, Transgenic ; Receptors, Antigen, T-Cell/genetics/*immunology ; T-Lymphocytes/*immunology ; }, abstract = {A technology to prime desired populations of T cells in the body-particularly those that possess low avidity against target antigen-would pave the way for the design of new types of vaccination for intractable infectious diseases or cancer. Here, we report such a technology based on positive feedback-driven, programmed self-assembly of peptide-major histocompatibility complex (pMHC) directly on the membrane of cognate T cells. Our design capitalizes on the unique features of the protein annexin V (ANXA5), which-in a concerted and synergistic manner-couples the early onset of TCR signaling by cognate pMHC with a surge in pMHC-TCR affinity, with repeated pMHC encounters, and with widespread TCR cross-linking. In our system, ANXA5 is linked to pMHC and firmly engages the plasma membrane of cognate T cells upon (and only upon) the early onset of TCR signaling. ANXA5, in turn, exerts a mechanical force that stabilizes interactions at the TCR-pMHC interface and facilitates repeated, serial pMHC encounters. Furthermore, ANXA5 quickly arranges into uniform 2D matrices, thereby prompting TCR cross-linking. Fusion of ANXA5 to pMHC augments lymphocyte activation by several orders of magnitude (>1,000-fold), bypasses the need for costimulation, and breaks tolerance against a model self-antigen in vivo. Our study opens the door to the application of synthetic, feedback-driven self-assembly platforms in immune modulation.}, } @article {pmid29632185, year = {2018}, author = {Lučić, I and Rathinaswamy, MK and Truebestein, L and Hamelin, DJ and Burke, JE and Leonard, TA}, title = {Conformational sampling of membranes by Akt controls its activation and inactivation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3940-E3949}, pmid = {29632185}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Enzyme Activation ; Humans ; *Models, Biological ; Phosphatidylinositol 3-Kinases/chemistry/genetics/*metabolism ; Phosphatidylinositol Phosphates/chemistry/genetics/*metabolism ; Phosphorylation ; Protein Domains ; Proto-Oncogene Proteins c-akt/chemistry/genetics/*metabolism ; }, abstract = {The protein kinase Akt controls myriad signaling processes in cells, ranging from growth and proliferation to differentiation and metabolism. Akt is activated by a combination of binding to the lipid second messenger PI(3,4,5)P3 and its subsequent phosphorylation by phosphoinositide-dependent kinase 1 and mechanistic target of rapamycin complex 2. The relative contributions of these mechanisms to Akt activity and signaling have hitherto not been understood. Here, we show that phosphorylation and activation by membrane binding are mutually interdependent. Moreover, the converse is also true: Akt is more rapidly dephosphorylated in the absence of PIP3, an autoinhibitory process driven by the interaction of its PH and kinase domains. We present biophysical evidence for the conformational changes in Akt that accompany its activation on membranes, show that Akt is robustly autoinhibited in the absence of PIP3 irrespective of its phosphorylation, and map the autoinhibitory PH-kinase interface. Finally, we present a model for the activation and inactivation of Akt by an ordered series of membrane binding, phosphorylation, dissociation, and dephosphorylation events.}, } @article {pmid29632184, year = {2018}, author = {Li, L and Tian, G and Peng, H and Meng, D and Wang, L and Hu, X and Tian, C and He, M and Zhou, J and Chen, L and Fu, C and Zhang, W and Hu, Z}, title = {New class of transcription factors controls flagellar assembly by recruiting RNA polymerase II in Chlamydomonas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4435-4440}, pmid = {29632184}, issn = {1091-6490}, support = {R01 GM100364/GM/NIGMS NIH HHS/United States ; }, mesh = {Chlamydomonas/genetics/*metabolism ; Flagella/genetics/*metabolism ; Gene Expression Regulation, Plant/*physiology ; Plant Proteins/genetics/*metabolism ; RNA Polymerase II/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic/physiology ; }, abstract = {Cells have developed regulatory mechanisms that underlie flagellar assembly and maintenance, including the transcriptional regulation of flagellar genes, an initial step for making flagella. Although transcriptional regulation of flagellar gene expression is required for flagellar assembly in Chlamydomonas, no transcription factor that regulates the transcription of flagellar genes has been identified. We report that X chromosome-associated protein 5 (XAP5) acts as a transcription factor to regulate flagellar assembly in Chlamydomonas While XAP5 proteins are evolutionarily conserved across diverse organisms and play vital roles in diverse biological processes, nothing is known about the biochemical function of any member of this important protein family. Our data show that loss of XAP5 leads to defects in flagellar assembly. Posttranslational modifications of XAP5 track flagellar length during flagellar assembly, suggesting that cells possess a feedback system that modulates modifications to XAP5. Notably, XAP5 regulates flagellar gene expression via directly binding to a motif containing a CTGGGGTG-core. Furthermore, recruitment of RNA polymerase II (Pol II) machinery for transcriptional activation depends on the activities of XAP5. Our data demonstrate that, through recruitment of Pol II, XAP5 defines a class of transcription factors for transcriptional regulation of ciliary genes. This work provides insights into the biochemical function of the XAP5 family and the fundamental biology of the flagellar assembly, which enhance our understanding of the signaling and functions of flagella.}, } @article {pmid29632183, year = {2018}, author = {Ahmed, L and Zhang, Y and Block, E and Buehl, M and Corr, MJ and Cormanich, RA and Gundala, S and Matsunami, H and O'Hagan, D and Ozbil, M and Pan, Y and Sekharan, S and Ten, N and Wang, M and Yang, M and Zhang, Q and Zhang, R and Batista, VS and Zhuang, H}, title = {Molecular mechanism of activation of human musk receptors OR5AN1 and OR1A1 by (R)-muscone and diverse other musk-smelling compounds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3950-E3958}, pmid = {29632183}, issn = {1091-6490}, support = {R01 DC014423/DC/NIDCD NIH HHS/United States ; R01 GM106121/GM/NIGMS NIH HHS/United States ; S10 OD018164/OD/NIH HHS/United States ; }, mesh = {Cycloparaffins/*chemistry ; HEK293 Cells ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; *Models, Molecular ; Mutagenesis, Site-Directed ; Protein Stability ; Protein Structure, Secondary ; Receptors, Odorant/*chemistry/genetics/metabolism ; }, abstract = {Understanding olfaction at the molecular level is challenging due to the lack of crystallographic models of odorant receptors (ORs). To better understand the molecular mechanism of OR activation, we focused on chiral (R)-muscone and other musk-smelling odorants due to their great importance and widespread use in perfumery and traditional medicine, as well as environmental concerns associated with bioaccumulation of musks with estrogenic/antiestrogenic properties. We experimentally and computationally examined the activation of human receptors OR5AN1 and OR1A1, recently identified as specifically responding to musk compounds. OR5AN1 responds at nanomolar concentrations to musk ketone and robustly to macrocyclic sulfoxides and fluorine-substituted macrocyclic ketones; OR1A1 responds only to nitromusks. Structural models of OR5AN1 and OR1A1 based on quantum mechanics/molecular mechanics (QM/MM) hybrid methods were validated through direct comparisons with activation profiles from site-directed mutagenesis experiments and analysis of binding energies for 35 musk-related odorants. The experimentally found chiral selectivity of OR5AN1 to (R)- over (S)-muscone was also computationally confirmed for muscone and fluorinated (R)-muscone analogs. Structural models show that OR5AN1, highly responsive to nitromusks over macrocyclic musks, stabilizes odorants by hydrogen bonding to Tyr260 of transmembrane α-helix 6 and hydrophobic interactions with surrounding aromatic residues Phe105, Phe194, and Phe207. The binding of OR1A1 to nitromusks is stabilized by hydrogen bonding to Tyr258 along with hydrophobic interactions with surrounding aromatic residues Tyr251 and Phe206. Hydrophobic/nonpolar and hydrogen bonding interactions contribute, respectively, 77% and 13% to the odorant binding affinities, as shown by an atom-based quantitative structure-activity relationship model.}, } @article {pmid29632182, year = {2018}, author = {Nair, P and Vilcek, J}, title = {Profile of Alexander Y. Rudensky, winner of the 2018 Vilcek Prize in Biomedical Science.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4301-4304}, pmid = {29632182}, issn = {1091-6490}, mesh = {*Awards and Prizes ; Biomedical Research/*history ; Breast Neoplasms/*immunology/pathology ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Male ; Portraits as Topic ; T-Lymphocytes, Regulatory/*immunology/pathology ; }, } @article {pmid29632181, year = {2018}, author = {Dörsam, B and Seiwert, N and Foersch, S and Stroh, S and Nagel, G and Begaliew, D and Diehl, E and Kraus, A and McKeague, M and Minneker, V and Roukos, V and Reißig, S and Waisman, A and Moehler, M and Stier, A and Mangerich, A and Dantzer, F and Kaina, B and Fahrer, J}, title = {PARP-1 protects against colorectal tumor induction, but promotes inflammation-driven colorectal tumor progression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4061-E4070}, pmid = {29632181}, issn = {1091-6490}, mesh = {Animals ; Cell Line, Tumor ; Colorectal Neoplasms/*enzymology/genetics/pathology/prevention & control ; Guanine/analogs & derivatives/metabolism ; Humans ; Mice ; Mice, Knockout ; Poly (ADP-Ribose) Polymerase-1/genetics/*metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; }, abstract = {Colorectal cancer (CRC) is one of the most common tumor entities, which is causally linked to DNA repair defects and inflammatory bowel disease (IBD). Here, we studied the role of the DNA repair protein poly(ADP-ribose) polymerase-1 (PARP-1) in CRC. Tissue microarray analysis revealed PARP-1 overexpression in human CRC, correlating with disease progression. To elucidate its function in CRC, PARP-1 deficient (PARP-1-/-) and wild-type animals (WT) were subjected to azoxymethane (AOM)/ dextran sodium sulfate (DSS)-induced colorectal carcinogenesis. Miniendoscopy showed significantly more tumors in WT than in PARP-1-/- mice. Although the lack of PARP-1 moderately increased DNA damage, both genotypes exhibited comparable levels of AOM-induced autophagy and cell death. Interestingly, miniendoscopy revealed a higher AOM/DSS-triggered intestinal inflammation in WT animals, which was associated with increased levels of innate immune cells and proinflammatory cytokines. Tumors in WT animals were more aggressive, showing higher levels of STAT3 activation and cyclin D1 up-regulation. PARP-1-/- animals were then crossed with O6-methylguanine-DNA methyltransferase (MGMT)-deficient animals hypersensitive to AOM. Intriguingly, PARP-1-/-/MGMT-/- double knockout (DKO) mice developed more, but much smaller tumors than MGMT-/- animals. In contrast to MGMT-deficient mice, DKO animals showed strongly reduced AOM-dependent colonic cell death despite similar O6-methylguanine levels. Studies with PARP-1-/- cells provided evidence for increased alkylation-induced DNA strand break formation when MGMT was inhibited, suggesting a role of PARP-1 in the response to O6-methylguanine adducts. Our findings reveal PARP-1 as a double-edged sword in colorectal carcinogenesis, which suppresses tumor initiation following DNA alkylation in a MGMT-dependent manner, but promotes inflammation-driven tumor progression.}, } @article {pmid29632180, year = {2018}, author = {Lim, S and Yu, Q and Gottlieb, SM and Chang, CW and Rockwell, NC and Martin, SS and Madsen, D and Lagarias, JC and Larsen, DS and Ames, JB}, title = {Correlating structural and photochemical heterogeneity in cyanobacteriochrome NpR6012g4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4387-4392}, pmid = {29632180}, issn = {1091-6490}, support = {R01 EY012347/EY/NEI NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/genetics ; Mutagenesis, Site-Directed ; Nostoc/*chemistry/genetics ; Phytochrome/*chemistry/genetics ; Protein Domains ; }, abstract = {Phytochrome photoreceptors control plant growth, development, and the shade avoidance response that limits crop yield in high-density agricultural plantings. Cyanobacteriochromes (CBCRs) are distantly related photosensory proteins that control cyanobacterial metabolism and behavior in response to light. Photoreceptors in both families reversibly photoconvert between two photostates via photoisomerization of linear tetrapyrrole (bilin) chromophores. Spectroscopic and biochemical studies have demonstrated heterogeneity in both photostates, but the structural basis for such heterogeneity remains unclear. We report solution NMR structures for both photostates of the red/green CBCR NpR6012g4 from Nostoc punctiforme In addition to identifying structural changes accompanying photoconversion, these structures reveal structural heterogeneity for residues Trp655 and Asp657 in the red-absorbing NpR6012g4 dark state, yielding two distinct environments for the phycocyanobilin chromophore. We use site-directed mutagenesis and fluorescence and absorbance spectroscopy to assign an orange-absorbing population in the NpR6012g4 dark state to the minority configuration for Asp657. This population does not undergo full, productive photoconversion, as shown by time-resolved spectroscopy and absorption spectroscopy at cryogenic temperature. Our studies thus elucidate the spectral and photochemical consequences of structural heterogeneity in a member of the phytochrome superfamily, insights that should inform efforts to improve photochemical or fluorescence quantum yields in the phytochrome superfamily.}, } @article {pmid29632179, year = {2018}, author = {Chen, H and Ma, B and Zhou, Y and He, SJ and Tang, SY and Lu, X and Xie, Q and Chen, SY and Zhang, JS}, title = {E3 ubiquitin ligase SOR1 regulates ethylene response in rice root by modulating stability of Aux/IAA protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4513-4518}, pmid = {29632179}, issn = {1091-6490}, mesh = {DNA-Binding Proteins/genetics/*metabolism ; Ethylenes/*metabolism ; Indoleacetic Acids/metabolism ; Oryza/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; Plant Roots/genetics/*metabolism ; Seedlings/genetics/metabolism ; Signal Transduction/physiology ; Ubiquitin-Protein Ligases/genetics/*metabolism ; }, abstract = {Plant hormones ethylene and auxin synergistically regulate plant root growth and development. Ubiquitin-mediated proteolysis of Aux/IAA transcriptional repressors by the E3 ubiquitin ligase SCFTIR1/AFB triggers a transcription-based auxin signaling. Here we show that rice (Oryza sativa L.) soil-surface rooting 1 (SOR1), which is a RING finger E3 ubiquitin ligase identified from analysis of a rice ethylene-insensitive mutant mhz2/sor1-2, controls root-specific ethylene responses by modulating Aux/IAA protein stability. SOR1 physically interacts with OsIAA26 and OsIAA9, which are atypical and canonical Aux/IAA proteins, respectively. SOR1 targets OsIAA26 for ubiquitin/26S proteasome-mediated degradation, whereas OsIAA9 protects the OsIAA26 protein from degradation by inhibiting the E3 activity of SOR1. Auxin promotes SOR1-dependent degradation of OsIAA26 by facilitating SCFOsTIR1/AFB2-mediated and SOR1-assisted destabilization of OsIAA9 protein. Our study provides a candidate mechanism by which the SOR1-OsIAA26 module acts downstream of the OsTIR1/AFB2-auxin-OsIAA9 signaling to modulate ethylene inhibition of root growth in rice seedlings.}, } @article {pmid29632178, year = {2018}, author = {Han, J and Peskin, CS}, title = {Spontaneous oscillation and fluid-structure interaction of cilia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4417-4422}, pmid = {29632178}, issn = {1091-6490}, mesh = {Cilia/physiology ; Dyneins/*metabolism ; Eukaryotic Cells/*physiology ; *Models, Biological ; }, abstract = {The exact mechanism to orchestrate the action of hundreds of dynein motor proteins to generate wave-like ciliary beating remains puzzling and has fascinated many scientists. We present a 3D model of a cilium and the simulation of its beating in a fluid environment. The model cilium obeys a simple geometric constraint that arises naturally from the microscopic structure of a real cilium. This constraint allows us to determine the whole 3D structure at any instant in terms of the configuration of a single space curve. The tensions of active links, which model the dynein motor proteins, follow a postulated dynamical law, and together with the passive elasticity of microtubules, this dynamical law is responsible for the ciliary motions. In particular, our postulated tension dynamics lead to the instability of a symmetrical steady state, in which the cilium is straight and its active links are under equal tensions. The result of this instability is a stable, wave-like, limit cycle oscillation. We have also investigated the fluid-structure interaction of cilia using the immersed boundary (IB) method. In this setting, we see not only coordination within a single cilium but also, coordinated motion, in which multiple cilia in an array organize their beating to pump fluid, in particular by breaking phase synchronization.}, } @article {pmid29632177, year = {2018}, author = {Shokri-Kojori, E and Wang, GJ and Wiers, CE and Demiral, SB and Guo, M and Kim, SW and Lindgren, E and Ramirez, V and Zehra, A and Freeman, C and Miller, G and Manza, P and Srivastava, T and De Santi, S and Tomasi, D and Benveniste, H and Volkow, ND}, title = {β-Amyloid accumulation in the human brain after one night of sleep deprivation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4483-4488}, pmid = {29632177}, issn = {1091-6490}, mesh = {Adult ; Aged ; Alzheimer Disease/diagnostic imaging/genetics/metabolism ; Amyloid beta-Peptides/genetics/*metabolism ; Apolipoproteins E/genetics ; Female ; Genotype ; Hippocampus/diagnostic imaging/*metabolism ; Humans ; Male ; Middle Aged ; Risk Factors ; Sleep Deprivation/*diagnostic imaging/genetics/*metabolism ; Thalamus/diagnostic imaging/*metabolism ; }, abstract = {The effects of acute sleep deprivation on β-amyloid (Aβ) clearance in the human brain have not been documented. Here we used PET and 18F-florbetaben to measure brain Aβ burden (ABB) in 20 healthy controls tested after a night of rested sleep (baseline) and after a night of sleep deprivation. We show that one night of sleep deprivation, relative to baseline, resulted in a significant increase in Aβ burden in the right hippocampus and thalamus. These increases were associated with mood worsening following sleep deprivation, but were not related to the genetic risk (APOE genotype) for Alzheimer's disease. Additionally, baseline ABB in a range of subcortical regions and the precuneus was inversely associated with reported night sleep hours. APOE genotyping was also linked to subcortical ABB, suggesting that different Alzheimer's disease risk factors might independently affect ABB in nearby brain regions. In summary, our findings show adverse effects of one-night sleep deprivation on brain ABB and expand on prior findings of higher Aβ accumulation with chronic less sleep.}, } @article {pmid29632176, year = {2018}, author = {Buri, P and Pellicciotti, F}, title = {Aspect controls the survival of ice cliffs on debris-covered glaciers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4369-4374}, pmid = {29632176}, issn = {1091-6490}, abstract = {Supraglacial ice cliffs exist on debris-covered glaciers worldwide, but despite their importance as melt hot spots, their life cycle is little understood. Early field observations had advanced a hypothesis of survival of north-facing and disappearance of south-facing cliffs, which is central for predicting the contribution of cliffs to total glacier mass losses. Their role as windows of energy transfer suggests they may explain the anomalously high mass losses of debris-covered glaciers in High Mountain Asia (HMA) despite the insulating debris, currently at the center of a debated controversy. We use a 3D model of cliff evolution coupled to very high-resolution topographic data to demonstrate that ice cliffs facing south (in the Northern Hemisphere) disappear within a few months due to enhanced solar radiation receipts and that aspect is the key control on cliffs evolution. We reproduce continuous flattening of south-facing cliffs, a result of their vertical gradient of incoming solar radiation and sky view factor. Our results establish that only north-facing cliffs are recurrent features and thus stable contributors to the melting of debris-covered glaciers. Satellite observations and mass balance modeling confirms that few south-facing cliffs of small size exist on the glaciers of Langtang, and their contribution to the glacier volume losses is very small ([Formula: see text]1%). This has major implications for the mass balance of HMA debris-covered glaciers as it provides the basis for new parameterizations of cliff evolution and distribution to constrain volume losses in a region where glaciers are highly relevant as water sources for millions of people.}, } @article {pmid29632175, year = {2018}, author = {Nakada, T and Kashihara, T and Komatsu, M and Kojima, K and Takeshita, T and Yamada, M}, title = {Physical interaction of junctophilin and the CaV1.1 C terminus is crucial for skeletal muscle contraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4507-4512}, pmid = {29632175}, issn = {1091-6490}, mesh = {Animals ; Calcium/metabolism ; Calcium Channels, L-Type/genetics/*metabolism ; Calcium Signaling/*physiology ; Cell Line ; Membrane Proteins/genetics/*metabolism ; Mice ; Muscle Contraction/*physiology ; Muscle Proteins/genetics/*metabolism ; Muscle, Skeletal/*metabolism ; Protein Domains ; Sarcolemma/genetics/metabolism ; }, abstract = {Close physical association of CaV1.1 L-type calcium channels (LTCCs) at the sarcolemmal junctional membrane (JM) with ryanodine receptors (RyRs) of the sarcoplasmic reticulum (SR) is crucial for excitation-contraction coupling (ECC) in skeletal muscle. However, the molecular mechanism underlying the JM targeting of LTCCs is unexplored. Junctophilin 1 (JP1) and JP2 stabilize the JM by bridging the sarcolemmal and SR membranes. Here, we examined the roles of JPs in localization and function of LTCCs. Knockdown of JP1 or JP2 in cultured myotubes inhibited LTCC clustering at the JM and suppressed evoked Ca2+ transients without disrupting JM structure. Coimmunoprecipitation and GST pull-down assays demonstrated that JPs physically interacted with 12-aa residues in the proximal C terminus of the CaV1.1. A JP1 mutant lacking the C terminus including the transmembrane domain (JP1ΔCT) interacted with the sarcolemmal/T-tubule membrane but not the SR membrane. Expression of this mutant in adult mouse muscles in vivo exerted a dominant-negative effect on endogenous JPs, impairing LTCC-RyR coupling at triads without disrupting JM morphology, and substantially reducing Ca2+ transients without affecting SR Ca2+ content. Moreover, the contractile force of the JP1ΔCT-expressed muscle was dramatically reduced compared with the control. Taken together, JPs recruit LTCCs to the JM through physical interaction and ensure robust ECC at triads in skeletal muscle.}, } @article {pmid29632174, year = {2018}, author = {Damian, M and Pons, V and Renault, P and M'Kadmi, C and Delort, B and Hartmann, L and Kaya, AI and Louet, M and Gagne, D and Ben Haj Salah, K and Denoyelle, S and Ferry, G and Boutin, JA and Wagner, R and Fehrentz, JA and Martinez, J and Marie, J and Floquet, N and Galès, C and Mary, S and Hamm, HE and Banères, JL}, title = {GHSR-D2R heteromerization modulates dopamine signaling through an effect on G protein conformation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4501-4506}, pmid = {29632174}, issn = {1091-6490}, mesh = {Dopamine/*chemistry/genetics/metabolism ; GTP-Binding Protein alpha Subunits, Gi-Go/*chemistry/genetics/metabolism ; Humans ; *Protein Multimerization ; Receptors, Dopamine D2/*chemistry/genetics/metabolism ; Receptors, Ghrelin/*chemistry/genetics/metabolism ; *Signal Transduction ; }, abstract = {The growth hormone secretagogue receptor (GHSR) and dopamine receptor (D2R) have been shown to oligomerize in hypothalamic neurons with a significant effect on dopamine signaling, but the molecular processes underlying this effect are still obscure. We used here the purified GHSR and D2R to establish that these two receptors assemble in a lipid environment as a tetrameric complex composed of two each of the receptors. This complex further recruits G proteins to give rise to an assembly with only two G protein trimers bound to a receptor tetramer. We further demonstrate that receptor heteromerization directly impacts on dopamine-mediated Gi protein activation by modulating the conformation of its α-subunit. Indeed, association to the purified GHSR:D2R heteromer triggers a different active conformation of Gαi that is linked to a higher rate of GTP binding and a faster dissociation from the heteromeric receptor. This is an additional mechanism to expand the repertoire of GPCR signaling modulation that could have implications for the control of dopamine signaling in normal and physiopathological conditions.}, } @article {pmid29632173, year = {2018}, author = {Canfield, DE and Zhang, S and Wang, H and Wang, X and Zhao, W and Su, J and Bjerrum, CJ and Haxen, ER and Hammarlund, EU}, title = {A Mesoproterozoic iron formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3895-E3904}, pmid = {29632173}, issn = {1091-6490}, abstract = {We describe a 1,400 million-year old (Ma) iron formation (IF) from the Xiamaling Formation of the North China Craton. We estimate this IF to have contained at least 520 gigatons of authigenic Fe, comparable in size to many IFs of the Paleoproterozoic Era (2,500-1,600 Ma). Therefore, substantial IFs formed in the time window between 1,800 and 800 Ma, where they are generally believed to have been absent. The Xiamaling IF is of exceptionally low thermal maturity, allowing the preservation of organic biomarkers and an unprecedented view of iron-cycle dynamics during IF emplacement. We identify tetramethyl aryl isoprenoid (TMAI) biomarkers linked to anoxygenic photosynthetic bacteria and thus phototrophic Fe oxidation. Although we cannot rule out other pathways of Fe oxidation, iron and organic matter likely deposited to the sediment in a ratio similar to that expected for anoxygenic photosynthesis. Fe reduction was likely a dominant and efficient pathway of organic matter mineralization, as indicated by organic matter maturation by Rock Eval pyrolysis combined with carbon isotope analyses: Indeed, Fe reduction was seemingly as efficient as oxic respiration. Overall, this Mesoproterozoic-aged IF shows many similarities to Archean-aged (>2,500 Ma) banded IFs (BIFs), but with an exceptional state of preservation, allowing an unprecedented exploration of Fe-cycle dynamics in IF deposition.}, } @article {pmid29632172, year = {2018}, author = {Bung, N and Roy, A and Chen, B and Das, D and Pradhan, M and Yasuda, M and New, MI and Desnick, RJ and Bulusu, G}, title = {Human hydroxymethylbilane synthase: Molecular dynamics of the pyrrole chain elongation identifies step-specific residues that cause AIP.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4071-E4080}, pmid = {29632172}, issn = {1091-6490}, mesh = {Amino Acid Substitution ; Humans ; Hydroxymethylbilane Synthase/*chemistry/genetics/metabolism ; *Molecular Dynamics Simulation ; *Mutation, Missense ; Porphyria, Acute Intermittent/*enzymology/genetics ; Protein Structure, Secondary ; Pyrroles/*chemistry/metabolism ; }, abstract = {Hydroxymethylbilane synthase (HMBS), the third enzyme in the heme biosynthetic pathway, catalyzes the head-to-tail condensation of four molecules of porphobilinogen (PBG) to form the linear tetrapyrrole 1-hydroxymethylbilane (HMB). Mutations in human HMBS (hHMBS) cause acute intermittent porphyria (AIP), an autosomal-dominant disorder characterized by life-threatening neurovisceral attacks. Although the 3D structure of hHMBS has been reported, the mechanism of the stepwise polymerization of four PBG molecules to form HMB remains unknown. Moreover, the specific roles of each of the critical active-site residues in the stepwise enzymatic mechanism and the dynamic behavior of hHMBS during catalysis have not been investigated. Here, we report atomistic studies of HMB stepwise synthesis by using molecular dynamics (MD) simulations, mutagenesis, and in vitro expression analyses. These studies revealed that the hHMBS active-site loop movement and cofactor turn created space for the elongating pyrrole chain. Twenty-seven residues around the active site and water molecules interacted to stabilize the large, negatively charged, elongating polypyrrole. Mutagenesis of these active-site residues altered the binding site, hindered cofactor binding, decreased catalysis, impaired ligand exit, and/or destabilized the enzyme. Based on intermediate stages of chain elongation, R26 and R167 were the strongest candidates for proton transfer to deaminate the incoming PBG molecules. Unbiased random acceleration MD simulations identified R167 as a gatekeeper and facilitator of HMB egress through the space between the enzyme's domains and the active-site loop. These studies identified the specific active-site residues involved in each step of pyrrole elongation, thereby providing the molecular bases of the active-site mutations causing AIP.}, } @article {pmid29632171, year = {2018}, author = {Lee, M and Batuecas, MT and Tomoshige, S and Domínguez-Gil, T and Mahasenan, KV and Dik, DA and Hesek, D and Millán, C and Usón, I and Lastochkin, E and Hermoso, JA and Mobashery, S}, title = {Exolytic and endolytic turnover of peptidoglycan by lytic transglycosylase Slt of Pseudomonas aeruginosa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4393-4398}, pmid = {29632171}, issn = {1091-6490}, support = {R01 GM061629/GM/NIGMS NIH HHS/United States ; T32 GM075762/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry ; Crystallography, X-Ray ; Glycoside Hydrolases/*chemistry ; Peptidoglycan/*chemistry ; Protein Domains ; Pseudomonas aeruginosa/*enzymology ; Structure-Activity Relationship ; }, abstract = {β-Lactam antibiotics inhibit cell-wall transpeptidases, preventing the peptidoglycan, the major constituent of the bacterial cell wall, from cross-linking. This causes accumulation of long non-cross-linked strands of peptidoglycan, which leads to bacterial death. Pseudomonas aeruginosa, a nefarious bacterial pathogen, attempts to repair this aberrantly formed peptidoglycan by the function of the lytic transglycosylase Slt. We document in this report that Slt turns over the peptidoglycan by both exolytic and endolytic reactions, which cause glycosidic bond scission from a terminus or in the middle of the peptidoglycan, respectively. These reactions were characterized with complex synthetic peptidoglycan fragments that ranged in size from tetrasaccharides to octasaccharides. The X-ray structure of the wild-type apo Slt revealed it to be a doughnut-shaped protein. In a series of six additional X-ray crystal structures, we provide insights with authentic substrates into how Slt is enabled for catalysis for both the endolytic and exolytic reactions. The substrate for the exolytic reaction binds Slt in a canonical arrangement and reveals how both the glycan chain and the peptide stems are recognized by the Slt. We document that the apo enzyme does not have a fully formed active site for the endolytic reaction. However, binding of the peptidoglycan at the existing subsites within the catalytic domain causes a conformational change in the protein that assembles the surface for binding of a more expansive peptidoglycan between the catalytic domain and an adjacent domain. The complexes of Slt with synthetic peptidoglycan substrates provide an unprecedented snapshot of the endolytic reaction.}, } @article {pmid29632170, year = {2018}, author = {Urlacher, SS and Ellison, PT and Sugiyama, LS and Pontzer, H and Eick, G and Liebert, MA and Cepon-Robins, TJ and Gildner, TE and Snodgrass, JJ}, title = {Tradeoffs between immune function and childhood growth among Amazonian forager-horticulturalists.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3914-E3921}, pmid = {29632170}, issn = {1091-6490}, mesh = {Adipose Tissue/*growth & development/*immunology ; Child ; *Child Development ; Child, Preschool ; Ecuador ; Female ; Humans ; *Immunity, Cellular ; *Immunity, Humoral ; Male ; Prospective Studies ; }, abstract = {Immune function is an energetically costly physiological activity that potentially diverts calories away from less immediately essential life tasks. Among developing organisms, the allocation of energy toward immune function may lead to tradeoffs with physical growth, particularly in high-pathogen, low-resource environments. The present study tests this hypothesis across diverse timeframes, branches of immunity, and conditions of energy availability among humans. Using a prospective mixed-longitudinal design, we collected anthropometric and blood immune biomarker data from 261 Amazonian forager-horticulturalist Shuar children (age 4-11 y old). This strategy provided baseline measures of participant stature, s.c. body fat, and humoral and cell-mediated immune activity as well as subsample longitudinal measures of linear growth (1 wk, 3 mo, 20 mo) and acute inflammation. Multilevel analyses demonstrate consistent negative effects of immune function on growth, with children experiencing up to 49% growth reduction during periods of mildly elevated immune activity. The direct energetic nature of these relationships is indicated by (i) the manifestation of biomarker-specific negative immune effects only when examining growth over timeframes capturing active competition for energetic resources, (ii) the exaggerated impact of particularly costly inflammation on growth, and (iii) the ability of children with greater levels of body fat (i.e., energy reserves) to completely avoid the growth-inhibiting effects of acute inflammation. These findings provide evidence for immunologically and temporally diverse body fat-dependent tradeoffs between immune function and growth during childhood. We discuss the implications of this work for understanding human developmental energetics and the biological mechanisms regulating variation in human ontogeny, life history, and health.}, } @article {pmid29632169, year = {2018}, author = {Pi, X and Tian, L and Dai, HE and Qin, X and Cheng, L and Kuang, T and Sui, SF and Shen, JR}, title = {Unique organization of photosystem I-light-harvesting supercomplex revealed by cryo-EM from a red alga.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4423-4428}, pmid = {29632169}, issn = {1091-6490}, mesh = {Cryoelectron Microscopy/methods ; Light-Harvesting Protein Complexes/*ultrastructure ; Photosystem I Protein Complex/*ultrastructure ; Protein Structure, Quaternary ; Rhodophyta/*enzymology/ultrastructure ; }, abstract = {Photosystem I (PSI) is one of the two photosystems present in oxygenic photosynthetic organisms and functions to harvest and convert light energy into chemical energy in photosynthesis. In eukaryotic algae and higher plants, PSI consists of a core surrounded by variable species and numbers of light-harvesting complex (LHC)I proteins, forming a PSI-LHCI supercomplex. Here, we report cryo-EM structures of PSI-LHCR from the red alga Cyanidioschyzon merolae in two forms, one with three Lhcr subunits attached to the side, similar to that of higher plants, and the other with two additional Lhcr subunits attached to the opposite side, indicating an ancient form of PSI-LHCI. Furthermore, the red algal PSI core showed features of both cyanobacterial and higher plant PSI, suggesting an intermediate type during evolution from prokaryotes to eukaryotes. The structure of PsaO, existing in eukaryotic organisms, was identified in the PSI core and binds three chlorophylls a and may be important in harvesting energy and in mediating energy transfer from LHCII to the PSI core under state-2 conditions. Individual attaching sites of LHCRs with the core subunits were identified, and each Lhcr was found to contain 11 to 13 chlorophylls a and 5 zeaxanthins, which are apparently different from those of LHCs in plant PSI-LHCI. Together, our results reveal unique energy transfer pathways different from those of higher plant PSI-LHCI, its adaptation to the changing environment, and the possible changes of PSI-LHCI during evolution from prokaryotes to eukaryotes.}, } @article {pmid29632168, year = {2018}, author = {Kalafatakis, K and Russell, GM and Harmer, CJ and Munafo, MR and Marchant, N and Wilson, A and Brooks, JC and Durant, C and Thakrar, J and Murphy, P and Thai, NJ and Lightman, SL}, title = {Ultradian rhythmicity of plasma cortisol is necessary for normal emotional and cognitive responses in man.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4091-E4100}, pmid = {29632168}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MR/J0125481/1//Medical Research Council/United Kingdom ; 089647/Z/09/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Brain/*metabolism ; Cognition/*physiology ; Emotions/*physiology ; Glucocorticoids/*metabolism ; Humans ; *Hydrocortisone/administration & dosage/pharmacokinetics ; Male ; }, abstract = {Glucocorticoids (GCs) are secreted in an ultradian, pulsatile pattern that emerges from delays in the feedforward-feedback interaction between the anterior pituitary and adrenal glands. Dynamic oscillations of GCs are critical for normal cognitive and metabolic function in the rat and have been shown to modulate the pattern of GC-sensitive gene expression, modify synaptic activity, and maintain stress responsiveness. In man, current cortisol replacement therapy does not reproduce physiological hormone pulses and is associated with psychopathological symptoms, especially apathy and attenuated motivation in engaging with daily activities. In this work, we tested the hypothesis that the pattern of GC dynamics in the brain is of crucial importance for regulating cognitive and behavioral processes. We provide evidence that exactly the same dose of cortisol administered in different patterns alters the neural processing underlying the response to emotional stimulation, the accuracy in recognition and attentional bias toward/away from emotional faces, the quality of sleep, and the working memory performance of healthy male volunteers. These data indicate that the pattern of the GC rhythm differentially impacts human cognition and behavior under physiological, nonstressful conditions and has major implications for the improvement of cortisol replacement therapy.}, } @article {pmid29631628, year = {2018}, author = {Mason, MR and Chambers, S and Dabdoub, SM and Thikkurissy, S and Kumar, PS}, title = {Characterizing oral microbial communities across dentition states and colonization niches.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {67}, pmid = {29631628}, issn = {2049-2618}, support = {T32-DE014320/DE/NIDCR NIH HHS/United States ; R01 DE022579/DE/NIDCR NIH HHS/United States ; F30- DE024940/DE/NIDCR NIH HHS/United States ; F30 DE024940/DE/NIDCR NIH HHS/United States ; T32 DE014320/DE/NIDCR NIH HHS/United States ; R01-DE022579/DE/NIDCR NIH HHS/United States ; }, mesh = {Biodiversity ; Cross-Sectional Studies ; *Dentition ; Gingiva/microbiology ; Humans ; Metagenome ; Metagenomics/methods ; *Microbiota ; Mouth/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Saliva/microbiology ; }, abstract = {METHODS: The present study aimed to identify patterns and processes in acquisition of oral bacteria and to characterize the microbiota of different dentition states and habitats. Mucosal, salivary, supragingival, and subgingival biofilm samples were collected from orally and systemically healthy children and mother-child dyads in predentate, primary, mixed, and permanent dentitions. 16S rRNA gene sequences were compared to the Human Oral Microbiome Database (HOMD). Functional potential was inferred using PICRUSt.

RESULTS: Unweighted and weighted UniFrac distances were significantly smaller between each mother-predentate dyad than infant-unrelated female dyads. Predentate children shared a median of 85% of species-level operational taxonomic units (s-OTUs) and 100% of core s-OTUs with their mothers. Maternal smoking, but not gender, mode of delivery, feeding habits, or type of food discriminated between predentate microbial profiles. The primary dentition demonstrated expanded community membership, structure, and function when compared to the predentate stage, as well as significantly lower similarity between mother-child dyads. The primary dentition also included 85% of predentate core s-OTUs. Subsequent dentitions exhibited over 90% similarity to the primary dentition in phylogenetic and functional structure. Species from the predentate mucosa as well as new microbial assemblages were identified in the primary supragingival and subgingival microbiomes. All individuals shared 65% of species between supragingival and subgingival habitats; however, the salivary microbiome exhibited less than 35% similarity to either habitat.

CONCLUSIONS: Within the limitations of a cross-sectional study design, we identified two definitive stages in oral bacterial colonization: an early predentate imprinting and a second wave with the eruption of primary teeth. Bacterial acquisition in the oral microbiome is influenced by the maternal microbiome. Personalization begins with the eruption of primary teeth; however, this is limited to phylogeny; functionally, individuals exhibit few differences, suggesting that microbial assembly may follow a defined schematic that is driven by the functional requirements of the ecosystem. This early microbiome forms the foundation upon which newer communities develop as more colonization niches emerge, and expansion of biodiversity is attributable to both introduction of new species and increase in abundance of predentate organisms.}, } @article {pmid29631623, year = {2018}, author = {Shkoporov, AN and Ryan, FJ and Draper, LA and Forde, A and Stockdale, SR and Daly, KM and McDonnell, SA and Nolan, JA and Sutton, TDS and Dalmasso, M and McCann, A and Ross, RP and Hill, C}, title = {Reproducible protocols for metagenomic analysis of human faecal phageomes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {68}, pmid = {29631623}, issn = {2049-2618}, support = {SFI/14/SP APC/B3032//Science Foundation Ireland/Ireland ; SFI/12/RC/2273//Science Foundation Ireland/Ireland ; N/A//Janssen Biotech, Inc/International ; }, mesh = {Bacteria/classification/genetics ; Bacteriophages/*genetics ; Feces/*virology ; *Gastrointestinal Microbiome ; Humans ; *Metagenome ; *Metagenomics/methods ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; }, abstract = {BACKGROUND: Recent studies have demonstrated that the human gut is populated by complex, highly individual and stable communities of viruses, the majority of which are bacteriophages. While disease-specific alterations in the gut phageome have been observed in IBD, AIDS and acute malnutrition, the human gut phageome remains poorly characterised. One important obstacle in metagenomic studies of the human gut phageome is a high level of discrepancy between results obtained by different research groups. This is often due to the use of different protocols for enriching virus-like particles, nucleic acid purification and sequencing. The goal of the present study is to develop a relatively simple, reproducible and cost-efficient protocol for the extraction of viral nucleic acids from human faecal samples, suitable for high-throughput studies. We also analyse the effect of certain potential confounding factors, such as storage conditions, repeated freeze-thaw cycles, and operator bias on the resultant phageome profile. Additionally, spiking of faecal samples with an exogenous phage standard was employed to quantitatively analyse phageomes following metagenomic sequencing. Comparative analysis of phageome profiles to bacteriome profiles was also performed following 16S rRNA amplicon sequencing.

RESULTS: Faecal phageome profiles exhibit an overall greater individual specificity when compared to bacteriome profiles. The phageome and bacteriome both exhibited moderate change when stored at + 4 °C or room temperature. Phageome profiles were less impacted by multiple freeze-thaw cycles than bacteriome profiles, but there was a greater chance for operator effect in phageome processing. The successful spiking of faecal samples with exogenous bacteriophage demonstrated large variations in the total viral load between individual samples.

CONCLUSIONS: The faecal phageome sequencing protocol developed in this study provides a valuable additional view of the human gut microbiota that is complementary to 16S amplicon sequencing and/or metagenomic sequencing of total faecal DNA. The protocol was optimised for several confounding factors that are encountered while processing faecal samples, to reduce discrepancies observed within and between research groups studying the human gut phageome. Rapid storage, limited freeze-thaw cycling and spiking of faecal samples with an exogenous phage standard are recommended for optimum results.}, } @article {pmid29631597, year = {2018}, author = {Tedla, M and Mehari, F and Kebede, H}, title = {A cross-sectional survey and follow up study on major dairy health problems in large and small scale urban farms in Mekelle, Tigray, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {236}, pmid = {29631597}, issn = {1756-0500}, mesh = {Animals ; Cattle ; Cattle Diseases/*epidemiology ; Communicable Diseases/*epidemiology/veterinary ; Cross-Sectional Studies ; Dairying/*statistics & numerical data ; Ethiopia/epidemiology ; Farms/*statistics & numerical data ; Female ; Follow-Up Studies ; Parasitic Diseases, Animal/*epidemiology ; Pregnancy ; Pregnancy Complications/*epidemiology/veterinary ; }, abstract = {OBJECTIVE: This study was conducted with the objective of estimating the incidence of major dairy health problems in the area.

RESULT: From a cross-sectional survey (n = 475) and follow up study (n = 68), an overall incidence of 43.00 and 29.02% was reported respectively. This study showed biting fly (9.51%), respiratory problems (7.80%), mastitis (5.13%), actinomycosis (5.12%), dystocia (4.42%), endoparasites (3.81%), retention fetal membrane (3.63%), tick infestation (2.91%), lameness (2.94%), vaginal and uterine prolepses (2.51%), skin related problem (1.70%) and abortion (1.70%) were the main dairy health problems identified. In addition, the follow up study revealed; retention fetal membrane (5.91%), tick infestation (5.91%), respiratory problem (2.91%), mastitis (2.94%), endoparasites (2.94%), lameness (2.94%), dystocia (2.94%), actinomycosis (1.53%) and skin related problems (1.53%). The incidence of dairy reproductive problems showed statistically significant variation among local and cross breeds (P < 0.05). Incidence of infectious diseases among dairy cows managed under intensive and semi-intensive management systems showed a significant difference (P < 0.05). Moreover, incidence of physical injury was also showed a significant difference among animal breeds and management system (P < 0.05). However, reproductive problems among management system and infectious diseases among breeds showed a significant difference (P > 0.05). Overall, this study showed dairy animals are exposed to various type of diseases.}, } @article {pmid29631571, year = {2018}, author = {Dimitrova, E and Caromile, LA and Laubenbacher, R and Shapiro, LH}, title = {The innate immune response to ischemic injury: a multiscale modeling perspective.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {50}, pmid = {29631571}, issn = {1752-0509}, support = {K01 CA188412/CA/NCI NIH HHS/United States ; R01 HL127449/HL/NHLBI NIH HHS/United States ; R01HL127449//National Heart, Lung, and Blood Institute/ ; }, abstract = {BACKGROUND: Cell death as a result of ischemic injury triggers powerful mechanisms regulated by germline-encoded Pattern Recognition Receptors (PRRs) with shared specificity that recognize invading pathogens and endogenous ligands released from dying cells, and as such are essential to human health. Alternatively, dysregulation of these mechanisms contributes to extreme inflammation, deleterious tissue damage and impaired healing in various diseases. The Toll-like receptors (TLRs) are a prototypical family of PRRs that may be powerful anti-inflammatory targets if agents can be designed that antagonize their harmful effects while preserving host defense functions. This requires an understanding of the complex interactions and consequences of targeting the TLR-mediated pathways as well as technologies to analyze and interpret these, which will then allow the simulation of perturbations targeting specific pathway components, predict potential outcomes and identify safe and effective therapeutic targets.

RESULTS: We constructed a multiscale mathematical model that spans the tissue and intracellular scales, and captures the consequences of targeting various regulatory components of injury-induced TLR4 signal transduction on potential pro-inflammatory or pro-healing outcomes. We applied known interactions to simulate how inactivation of specific regulatory nodes affects dynamics in the context of injury and to predict phenotypes of potential therapeutic interventions. We propose rules to link model behavior to qualitative estimates of pro-inflammatory signal activation, macrophage infiltration, production of reactive oxygen species and resolution. We tested the validity of the model by assessing its ability to reproduce published data not used in its construction.

CONCLUSIONS: These studies will enable us to form a conceptual framework focusing on TLR4-mediated ischemic repair to assess potential molecular targets that can be utilized therapeutically to improve efficacy and safety in treating ischemic/inflammatory injury.}, } @article {pmid29631566, year = {2018}, author = {Huang, Y and Cui, X and Cen, H and Wang, K and Zhang, Y}, title = {Transcriptomic analysis reveals vacuolar Na+ (K+)/H+ antiporter gene contributing to growth, development, and defense in switchgrass (Panicum virgatum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {57}, pmid = {29631566}, issn = {1471-2229}, support = {2014BAD23B03-02;2012AA101801//Ministry of Science and Technology of the People's Republic of China/ ; 31672478//National Natural Science Foundation of China/ ; 6162016//Natural Science Foundation of Beijing Municipality/ ; }, mesh = {Gene Expression Regulation, Plant/genetics/physiology ; Panicum/genetics/*metabolism ; Plants, Genetically Modified/genetics/*metabolism ; Sodium-Hydrogen Exchangers/genetics/*metabolism ; Transcriptome/*genetics ; Vacuoles/*metabolism ; }, abstract = {BACKGROUND: Intracellular Na+ (K+)/H+ antiporters (NHXs) have pivotal functions in regulating plant growth, development, and resistance to a range of stresses. To gain insight into the molecular events underlying their actions in switchgrass (Panicum virgatum L.), we analyzed transcriptomic changes between PvNHX1-overexpression transgenic lines and wild-type (WT) plants using RNA sequencing (RNA-seq) technology.

RESULTS: The comparison of transcriptomic data from the WT and transgenic plants revealed a large number of differentially expressed genes (DEGs) in the latter. Gene ontology (GO) and KEGG pathway analyses showed that these DEGs were associated with a wide range of functions, and participated in many biological processes. For example, we found that PvNHX1 had an important role in plant growth through its regulation of photosynthetic activity and cell expansion. In addition, PvNHX1 regulated K+ homeostasis, cell expansion and pollen development, indicating that it has unique and specific roles in flower development. We also found that transgenic switchgrass exhibited a higher level of transcription of defense-related genes, especially those involved in disease resistance.

CONCLUSION: We showed that PvNHX1 had an important role in plant growth and development through its regulation of photosynthetic activity, cell expansion, K+ homeostasis, and pollen development. Additionally, PvNHX1 overexpression activated a complex signal transduction network in response to various biotic and abiotic stresses. In relation to plant growth, development, and defense responses, PvNHX1 also had a vital regulatory role in the formation of a series of plant hormones and transcription factors (TFs). The reliability of the RNA-seq data was confirmed by quantitative real-time PCR. Our data provide a valuable foundation for further research into the molecular mechanisms and physiological roles of NHXs in plants.}, } @article {pmid29631055, year = {2018}, author = {Chaney, ME and Piontkivska, H and Tosi, AJ}, title = {Retained duplications and deletions of CYP2C genes among primates.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {204-212}, doi = {10.1016/j.ympev.2018.03.037}, pmid = {29631055}, issn = {1095-9513}, mesh = {Animals ; Cytochrome P-450 Enzyme System/*genetics ; Evolution, Molecular ; *Gene Deletion ; *Gene Duplication ; Genome, Human ; Humans ; Introns/genetics ; Likelihood Functions ; Models, Genetic ; Multigene Family ; Phylogeny ; Primates/*genetics ; Selection, Genetic ; }, abstract = {The human genome encodes about 60 functional enzymes of the cytochrome P450 superfamily, including four functional enzymes of the cytochrome P450 2C (CYP2C) subfamily. These enzymes have been shown to metabolize drugs and xenobiotic toxins, such as those in the diet, and are therefore of great importance for biomedical research and applications. While the pharmacology of P450 enzymes has been studied extensively, our understanding of molecular evolution of this gene family is incomplete, in part because a great variation exists in the number of CYP2C homologs across genomes. In humans, the enzymes encoded by these genes are responsible for the metabolism of more than 20% of clinical drugs, but this is not the naturalistic function of these enzymes, which is the metabolism of xenobiotics such as plant secondary metabolites. In this paper, we sought to correlate evolutionary relationships among primate CYP2C genes with known dietary profiles from these species, testing the hypothesis that these genes have evolved under the pressure of dietary toxins. Aside from a small number of deeply divergent genes, primate CYP2C paralogs form three separate clades: CYP2C18, CYP2C9/CYP2C19, and CYP2C8/CYP2C20. Our results showed that the CYP2C18 gene has been separately lost in Nomascus leucogenys and the Panini genomes, and there is no evidence that this gene has been under any positive selection among primates. While CYP2C20 has been retained in cercopithecoids, orthologous loci were separately lost in platyrrhines and hominoids. Notably, nine codons exhibited signature of positive selection. Finally, the CYP2C19 locus was duplicated in basal catarrhines, resulting in the birth of CYP2C9; but the ancestral locus was only retained in hominoid taxa. Overall, our findings support the hypothesis that primate CYP2C genes have evolved in response to selective pressures provided by dietary toxins, although not all gene clusters have evolved in the same manner. Our results may indicate an evolutionarily deep difference in ecology or physiology among higher-order primate taxa.}, } @article {pmid29631054, year = {2018}, author = {Alström, P and Rheindt, FE and Zhang, R and Zhao, M and Wang, J and Zhu, X and Gwee, CY and Hao, Y and Ohlson, J and Jia, C and Prawiradilaga, DM and Ericson, PGP and Lei, F and Olsson, U}, title = {Complete species-level phylogeny of the leaf warbler (Aves: Phylloscopidae) radiation.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {141-152}, doi = {10.1016/j.ympev.2018.03.031}, pmid = {29631054}, issn = {1095-9513}, mesh = {Animals ; Cytochromes b/genetics ; *Phylogeny ; Songbirds/*classification ; Species Specificity ; }, abstract = {The leaf warbler radiation (Aves: Phylloscopidae) has undergone a c. 50% increase in the number of recognised species over the last three decades, mainly as a result of analyses of vocalisations and DNA. Using a multilocus dataset for all of the species in this family, and multispecies coalescent-based as well as concatenation methods, we provide the first complete species-level phylogeny for this important group, as well as an estimate of the timing of diversification. The most recent common ancestor for the family was dated at 11.7 million years ago (mya) (95% highest posterior density 9.8-13.7 mya), and divergence times between sister species ranged from 0.5 mya (0.3-0.8 mya) to 6.1 mya (4.8-7.5 mya). Based on our results, we support synonymising Seicercus with Phylloscopus, which results in a monogeneric Phylloscopidae. We discuss the pros and cons of this treatment,and we argue againstproliferation of taxonomic names,and conclude that a large monogeneric Phylloscopidae leads to the fewest taxonomic changes compared to traditional classifications. We briefly discuss morphological evolution in the light of the phylogeny. The time calibrated phylogeny is a major improvement compared to previous studies based on a smaller number of species and loci and can provide a basis for future studies of other aspects of phylloscopid evolution.}, } @article {pmid29631053, year = {2018}, author = {Chen, Y and Hammer, EE and Richards, VP}, title = {Phylogenetic signature of lateral exchange of genes for antibiotic production and resistance among bacteria highlights a pattern of global transmission of pathogens between humans and livestock.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {255-264}, doi = {10.1016/j.ympev.2018.03.034}, pmid = {29631053}, issn = {1095-9513}, mesh = {Animals ; Anti-Bacterial Agents/*biosynthesis ; Bacteria/*classification/genetics ; Cattle ; DNA Transposable Elements/genetics ; Drug Resistance, Bacterial/*genetics ; Gene Order ; Gene Transfer, Horizontal/*genetics ; *Genes, Bacterial ; Haplotypes/genetics ; Humans ; Likelihood Functions ; *Livestock ; Operon/genetics ; *Phylogeny ; Species Specificity ; Swine ; Virulence Factors ; Zoonoses/*microbiology/*transmission ; }, abstract = {The exchange of bacterial virulence factors driven by lateral gene transfer (LGT) can help indicate possible bacterial transmission among different hosts. Specifically, overlaying the phylogenetic signal of LGT among bacteria onto the distribution of respective isolation sources (hosts) can indicate patterns of transmission among these hosts. Here, we apply this approach towards a better understanding of patterns of bacterial transmission between humans and livestock. We utilize comparative genomics to trace patterns of LGT for an 11-gene operon responsible for the production of the antibiotic nisin and infer transmission of bacteria among respective host species. A total of 147 bacterial genomes obtained from NCBI were determined to contain the complete operon. Isolated from human, porcine and bovine hosts, these genomes represented six Streptococcus and one Staphylococcus species. Phylogenetic analyses of the operon sequences revealed a signature of frequent and recent lateral gene transfer that indicated extensive bacterial transmission between humans and pigs. For 11 isolates, we detected a Tn916-like transposon inserted into the operon. The transposon contained the tetM gene (tetracycline resistance) and additional phylogenetic analyses indicated transmission among human and animal hosts. The bacteria possessing the nisin operon and transposon were isolated from hosts distributed globally. These findings possibly reflect both the globalization of the food industry and an increasingly mobile and expanding human population. In addition to concerns regarding zoonosis, these findings also highlight the potential threat to livestock worldwide due to reverse zoonosis.}, } @article {pmid29631052, year = {2018}, author = {Zhou, W and Ji, X and Obata, S and Pais, A and Dong, Y and Peet, R and Xiang, QJ}, title = {Resolving relationships and phylogeographic history of the Nyssa sylvatica complex using data from RAD-seq and species distribution modeling.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {1-16}, doi = {10.1016/j.ympev.2018.04.001}, pmid = {29631052}, issn = {1095-9513}, mesh = {Bayes Theorem ; Genetic Loci ; *Models, Theoretical ; Nyssa/*classification/*genetics ; Phylogeny ; *Phylogeography ; Polymorphism, Single Nucleotide/genetics ; Sequence Analysis, DNA/*methods ; Species Specificity ; Time Factors ; }, abstract = {Nyssa sylvatica complex consists of several woody taxa occurring in eastern North America. These taxa were recognized as two or three species including three or four varieties by different authors. Due to high morphological similarities and complexity of morphological variation, classification and delineation of taxa in the group have been difficult and controversial. Here we employ data from RAD-seq to elucidate the genetic structure and phylogenetic relationships within the group. Using the genetic evidence, we evaluate previous classifications and delineate species. We also employ Species Distribution Modeling (SDM) to evaluate impacts of climatic changes on the ranges of the taxa and to gain insights into the relevant refugia in eastern North America. Results from Molecular Variance Analysis (AMOVA), STRUCTURE, phylogenetic analyses using Maximum likelihood, Bayesian Inference, and Splittree methods of RAD-seq data strongly support a two-clade pattern, largely separating samples of N. sylvatica from those of N. biflora-N. ursina mix. Divergence time analysis with BEAST suggests the two clades diverged in the mid Miocene. The ancestor of the present trees of N. sylvatica was suggested to be in the Pliocene and that of N. biflora-N. ursina mix in the end of the Miocene. Results from SDM predicted a smaller range in the southern part of the species present range of each clade during the Last Glacial Maximum (LGM). A northward expansion of the ranges during interglacial period and a northward shift of the ranges in the future under a model of global warming were also predicted. Our results support the recognition of two species in the complex, N. sylvatica and N. biflora, following the phylogenetic species concept. We found no genetic evidence supporting recognitions of intraspecific taxa. However, we propose subsp. ursina and subsp. biflora within N. biflora due to their distinction in habits, distributions, and habitats. Our results further support movements of trees in eastern North America in response to climatic changes. Finally, our study demonstrates that RAD-seq data and a combination of population genomics and SDM are valuable in resolving relationship and biogeographic history of closely related species that are taxonomically difficult.}, } @article {pmid29631051, year = {2018}, author = {Johansson, US and Irestedt, M and Qu, Y and Ericson, PGP}, title = {Phylogenetic relationships of rollers (Coraciidae) based on complete mitochondrial genomes and fifteen nuclear genes.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {17-22}, doi = {10.1016/j.ympev.2018.03.030}, pmid = {29631051}, issn = {1095-9513}, mesh = {Animals ; Cell Nucleus/*genetics ; DNA, Mitochondrial/genetics ; *Genome, Mitochondrial ; Likelihood Functions ; Passeriformes/*classification/*genetics ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The rollers (Coraciidae) constitute a relative small avian family with ca. 12 species distributed in Africa, western and southern Eurasia, and eastern Australia. In this study we examine the phylogenetic relationships of all species currently recognized in the family, including two taxa whose taxonomic status is currently contested. By using shotgun sequencing on degraded DNA from museum study skins we have been able to recover complete mitochondrial genomes as well as 15 nuclear genes for in total 16 taxa. The gene sequences were analyzed both concatenated in a maximum likelihood framework as well in a species tree approach using MP-EST. The different analytical approaches yield similar, highly supported trees and support the current division of the rollers into two genera, Coracias and Eurystomus. The only conflict relates to the placement of the Blue-bellied Roller (C. cyanogaster), where the mitochondrial, and the concatenated nuclear and mitochondrial data set, place this taxon as sister to the other Coracias species, whereas nuclear data and the species tree analysis place it as the sister taxon of C. naevia and C. spatulatus. All analyses place the Eurasian roller (C. garrulus) with the two African species, Abyssinian Roller (C. abyssinica) and Liliac-breasted Roller (C. caudatus), and place this clade as the sister group to the Asian Coracias rollers. In addition, our results support a sister group relationship between the morphologically rather dissimilar Purple Roller (C. naevia) and Racquet-tailed Roller (C. spatulatus) and also support the division of Eurystomus in an African and an Asian clade. However, within the Asian clade the Azure Roller (E. azureus) from Halmahera appears to be nested within the Dollarbird (E. orientalis), indicating that that this taxon is a morphological divergent, but a rather recent offshoot, of the widespread Dollarbird. Similarly, the Purple-winged Roller (C. temminickii) from Sulawesi group together with C. benghalensis affinis from Southeast Asia and these two in turn comprises the sister group to C. benghalensis benghalensis from India and western Asia.}, } @article {pmid29630866, year = {2018}, author = {Powers, AK and Boggs, TE and Gross, JB}, title = {Canal neuromast position prefigures developmental patterning of the suborbital bone series in Astyanax cave- and surface-dwelling fish.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {252-261}, pmid = {29630866}, issn = {1095-564X}, support = {R01 DE025033/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/*physiology ; Characiformes/*embryology ; Orbit/*embryology ; Osteogenesis/*physiology ; }, abstract = {Developmental patterning is a complex biological phenomenon, involving integrated cellular and molecular signaling across diverse tissues. In Astyanax cavefish, the lateral line sensory system is dramatically expanded in a region of the cranium marked by significant bone abnormalities. This system provides the opportunity to understand how facial bone patterning can become altered through sensory system changes. Here we investigate a classic postulation that mechanosensory receptor neuromasts seed intramembranous facial bones in aquatic vertebrates. Using an in vivo staining procedure across individual life history, we observed infraorbital canal neuromasts serving as sites of ossification for suborbital bones. The manner in which cavefish departed from the stereotypical and symmetrical canal neuromast patterns of closely-related surface-dwelling fish were associated with specific changes to the suborbital bone complex. For instance, bony fusion, rarely observed in surface fish, was associated with shorter distances between canal neuromasts in cavefish, suggesting that closer canal neuromasts result in bony fusions. Additionally, cavefish lacking the sixth suborbital bone (SO6) uniformly lacked the associated (sixth) canal neuromast. This study suggests that patterning of canal neuromasts may impact spatial position of suborbital bones across development. The absence of an eye and subsequent orbital collapse in cavefish appears to influence positional information normally inherent to the infraorbital canal. These alterations result in coordinated changes to adult neuromast and bone structures. This work highlights complex interactions between visual, sensory and bony tissues during development that explain certain abnormal craniofacial features in cavefish.}, } @article {pmid29630684, year = {2018}, author = {Halbeisen, F and Hogg, C and Alanin, MC and Bukowy-Bieryllo, Z and Dasi, F and Duncan, J and Friend, A and Goutaki, M and Jackson, C and Keenan, V and Harris, A and Hirst, RA and Latzin, P and Marsh, G and Nielsen, K and Norris, D and Pellicer, D and Reula, A and Rubbo, B and Rumman, N and Shoemark, A and Walker, WT and Kuehni, CE and Lucas, JS}, title = {Proceedings of the 2nd BEAT-PCD conference and 3rd PCD training school: part 1.}, journal = {BMC proceedings}, volume = {12}, number = {Suppl 2}, pages = {1}, pmid = {29630684}, issn = {1753-6561}, support = {MC_U142670370//Medical Research Council/United Kingdom ; }, abstract = {Primary ciliary dyskinesia (PCD) is a rare heterogenous condition that causes progressive suppurative lung disease, chronic rhinosinusitis, chronic otitis media, infertility and abnormal situs. 'Better Experimental Approaches to Treat Primary Ciliary Dyskinesia' (BEAT-PCD) is a network of scientists and clinicians coordinating research from basic science through to clinical care with the intention of developing treatments and diagnostics that lead to improved long-term outcomes for patients. BEAT-PCD activities are supported by EU funded COST Action (BM1407). The second BEAT-PCD conference, and third PCD training school were held jointly in April 2017 in Valencia, Spain. Presentations and workshops focussed on advancing the knowledge and skills relating to PCD in: basic science, epidemiology, diagnostic testing, clinical management and clinical trials. The multidisciplinary conference provided an interactive platform for exchanging ideas through a program of lectures, poster presentations, breakout sessions and workshops. Three working groups met to plan consensus statements. Progress with BEAT-PCD projects was shared and new collaborations were fostered. In this report, we summarize the meeting, highlighting developments made during the meeting.}, } @article {pmid29629855, year = {2018}, author = {Hou, J and Zhao, YJ and Zhu, L and Cui, HL}, title = {Salinirubellus salinus gen. nov., sp. nov., isolated from a marine solar saltern.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1874-1878}, doi = {10.1099/ijsem.0.002757}, pmid = {29629855}, issn = {1466-5034}, mesh = {Base Composition ; China ; DNA, Archaeal/genetics ; Fatty Acids/chemistry ; Genes, Archaeal ; Glycolipids/chemistry ; Halobacteriaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; *Water Microbiology ; }, abstract = {A halophilic archaeal strain, designated ZS-35-S2T, was isolated from Zhoushan marine solar saltern in Zhejiang Province, China. Cells were pleomorphic, Gram-stain-negative and formed red-pigmented colonies on agar plates. The cells lysed in distilled water and the minimal NaCl concentration to prevent cell lysis was 8 % (w/v). Strain ZS-35-S2T was able to grow at 25-50 °C (optimum, 37 °C), with 1.4-4.8 M NaCl (optimum, 2.1 M), with 0-1.0 M MgCl2 (optimum, 0.1 M) and at pH 5.0-9.5 (optimum, pH 7.5). Phylogenetic tree reconstructions based on 16S rRNA genes and rpoB' genes revealed that strain ZS-35-S2T was distinct from the related genera Halomarina, Natronomonas, Halorientalis, Salinirubrum and Halobaculum of the order Halobacteriales. The major polar lipids of the strain were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester and three unidentified glycolipids. The two major glycolipids were chromatographically identical to S-DGD-1 and DGD-1, respectively. The DNA G+C content of strain ZS-35-S2T is 67.0 mol%. The phenotypic, chemotaxonomic and phylogenetic properties suggested that strain ZS-35-S2T (=CGMCC 1.12551T=JCM 30036T) represents a novel species of a new genus within the order Halobacteriales, for which the name Salinirubellus salinus gen. nov., sp. nov. is proposed.}, } @article {pmid29629854, year = {2018}, author = {Cai, H and He, W and Yanan, W and Yan, Z and Wang, C and Xu, H and Shao, K}, title = {Flavobacterium aurantiibacter sp. nov., an orange-pigmented bacterium isolated from cyanobacterial aggregates in a eutrophic lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {6}, pages = {1839-1844}, doi = {10.1099/ijsem.0.002741}, pmid = {29629854}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Lakes/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A bacterial strain, designated TH167T, was isolated from cyanobacterial aggregates in eutrophic Lake Taihu in China. Cells were observed to be slightly curved rod-shaped, motile by gliding, aerobic, Gram-stain-negative, proteorhodopsin-containing. Optimal growth was obtained at pH 7.0 (range: 6.0-9.0), 28 °C (range: 4-32 °C) and 0 % (w/v) NaCl (range: 0-2.0 %) in Reasoner's 2A broth. No growth was observed at 37 °C. The cells were found to be positive for catalase and oxidase activities. The major fatty acids (>10 %) were identified as iso-C15 : 0, iso-C15 : 1 G and anteiso-C15 : 0. The major polar lipids of the isolate comprised phosphatidylethanolamine, one unidentified phospholipid and two unidentified aminolipids. The major respiratory quinone was menaquinone-6. The genomic G+C content of strain TH167T was 40.4 mol% based on total genome calculations. Based on similarities of 16S rRNA gene sequences, strain TH167T was affiliated with the genus Flavobacterium, exhibiting the highest sequence similarities to Flavobacterium eburneum SA31T (94.16 %), Flavobacterium yanchengensehgT (94.09 %) and Flavobacterium lacus NP180T (93.95 %). The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis suggested that strain TH167T represented a novel species within the genus Flavobacterium, for which the name Flavobacterium aurantiibacter sp. nov. is proposed. The type strain is TH167T (=CGMCC 1.15805T=LMG 29719T).}, } @article {pmid29628800, year = {2018}, author = {Landuyt, D and Perring, MP and Seidl, R and Taubert, F and Verbeeck, H and Verheyen, K}, title = {Modelling understorey dynamics in temperate forests under global change-Challenges and perspectives.}, journal = {Perspectives in plant ecology, evolution and systematics}, volume = {31}, number = {}, pages = {44-54}, pmid = {29628800}, issn = {1433-8319}, support = {Y 895//Austrian Science Fund FWF/Austria ; }, abstract = {The understorey harbours a substantial part of vascular plant diversity in temperate forests and plays an important functional role, affecting ecosystem processes such as nutrient cycling and overstorey regeneration. Global change, however, is putting these understorey communities on trajectories of change, potentially altering and reducing their functioning in the future. Developing mitigation strategies to safeguard the diversity and functioning of temperate forests in the future is challenging and requires improved predictive capacity. Process-based models that predict understorey community composition over time, based on first principles of ecology, have the potential to guide mitigation endeavours but such approaches are rare. Here, we review fourteen understorey modelling approaches that have been proposed during the last three decades. We evaluate their inclusion of mechanisms that are required to predict the impact of global change on understorey communities. We conclude that none of the currently existing models fully accounts for all processes that we deem important based on empirical and experimental evidence. Based on this review, we contend new models are needed to project the complex impacts of global change on forest understoreys. Plant functional traits should be central to such future model developments, as they drive community assembly processes and provide valuable information on the functioning of the understorey. Given the important role of the overstorey, a coupling of understorey models to overstorey models will be essential to predict the impact of global change on understorey composition and structure, and how it will affect the functioning of temperate forests in the future.}, } @article {pmid29628266, year = {2018}, author = {Pujol, B and Blanchet, S and Charmantier, A and Danchin, E and Facon, B and Marrot, P and Roux, F and Scotti, I and Teplitsky, C and Thomson, CE and Winney, I}, title = {The Missing Response to Selection in the Wild.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {337-346}, pmid = {29628266}, issn = {1872-8383}, support = {337365//European Research Council/International ; }, mesh = {Animals ; Animals, Wild/*genetics ; *Biological Evolution ; *Conservation of Natural Resources ; *Genetic Variation ; *Selection, Genetic ; }, abstract = {Although there are many examples of contemporary directional selection, evidence for responses to selection that match predictions are often missing in quantitative genetic studies of wild populations. This is despite the presence of genetic variation and selection pressures - theoretical prerequisites for the response to selection. This conundrum can be explained by statistical issues with accurate parameter estimation, and by biological mechanisms that interfere with the response to selection. These biological mechanisms can accelerate or constrain this response. These mechanisms are generally studied independently but might act simultaneously. We therefore integrated these mechanisms to explore their potential combined effect. This has implications for explaining the apparent evolutionary stasis of wild populations and the conservation of wildlife.}, } @article {pmid29628118, year = {2018}, author = {Gunnell, GF and Manthi, FK}, title = {Pliocene bats (Chiroptera) from Kanapoi, Turkana Basin, Kenya.}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2018.01.001}, pmid = {29628118}, issn = {1095-8606}, abstract = {Fossil bats from the Pliocene of Africa are extremely rare, especially in East Africa where meager records have been reported only from two localities in the Omo River Basin Shungura Formation and from a scattering of localities in the Afar Depression, both in Ethiopia. Here we report on a diverse assemblage of bats from Kanapoi in the Turkana Basin that date to approximately 4.19 million years ago. The Kanapoi bat community consists of four different species of fruit bats including a new genus and two new species as well as five species of echolocating bats, the most common of which are two new species of the molossid genus Mops. Additionally, among the echolocating bats, a new species of the emballonurid Saccolaimus is documented at Kanapoi along with an additional Saccolaimus species and a potentially new species of the nycterid Nycteris. Compared to other East African Pliocene bat assemblages, the Kanapoi bat community is unique in preserving molossids and curiously lacks any evidence of cave dwelling bats like rhinolophids or hipposiderids, which are both common at other East African sites. The bats making up the Kanapoi community all typically roost in trees, with some preferring deeper forests and larger trees (molossids), while the others (pteropodids, nycterids and emballonurids) roost in trees near open areas. Living fruit bats that are related to Kanapoi species typically forage for fruits along the margins of forests and in open savannah. The echolocating forms from Kanapoi consist of groups that aerially hawk for insects in open areas between patches of forest and along water courses. The habitats preferred by living relatives of the Kanapoi bats are in agreement with those constructed for Kanapoi based on other lines of evidence.}, } @article {pmid29627517, year = {2018}, author = {Yang, LE and Meng, Y and Peng, DL and Nie, ZL and Sun, H}, title = {Molecular phylogeny of Galium L. of the tribe Rubieae (Rubiaceae) - Emphasis on Chinese species and recognition of a new genus Pseudogalium.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {221-232}, doi = {10.1016/j.ympev.2018.04.004}, pmid = {29627517}, issn = {1095-9513}, mesh = {Bayes Theorem ; China ; DNA, Chloroplast/genetics ; Galium/*classification/*genetics ; Likelihood Functions ; *Phylogeny ; Species Specificity ; }, abstract = {Galium L. is the largest genus in the tribe Rubieae, with about 667 species distributed worldwide. Previous researches mainly focused on species from the Americas and Europe. In the present paper, we greatly increased the number of samples examined from eastern Asia (especially China), representing the most comprehensive sampling of Galium to date. A total of 194 species and variations (subspecies) of Galium were sampled to determine phylogenetic relationships, using two nuclear and five chloroplast markers. Our data are largely consistent with all previous phylogenetic results and confirmed that Galium is non-monophyletic, as are most of its sections. Most members of Galium, including the Chinese taxa, fall into three large clades mixed with other genera from the Galium s.l. group; the exception being the distinct Galium paradoxum Maxim., the first diverged lineage in the Galium s.l. group, which was treated as a new genus (Pseudogalium L.-E. Yang, Z.-L. Nie & H. Sun, gen. nov.). The Galium s.s is a well-supported clade comprised entirely of Galium species, usually with six or more leaves per whorl, mostly from the Old World. Samples from G. maximowiczii (Kom.) Pobed, G. sect. Depauperata and sect. Aparinoides, together with a few from Asperula sect. Glabella and Microphysa (Schrenk ex Fisch. & C.A. Mey.) Pobed., form the second clade. The third clade comprises taxa purely from Galium that usually have four leaves per whorl, from both the New and Old World. Our results also indicated that the monotypic genus Microphysa should be retained and clarified phylogenetic relationships of some specific confused taxa from China. Unlike prior inferences, the combination of opposite leaves associated with two stipules is proposed as the ancestral characteristic of the Galium s.l. group and even the tribe. In addition, the shapes of different corolla and inflorescence types are important for distinguishing some taxa within Rubieae.}, } @article {pmid29627269, year = {2018}, author = {Sanogo, B and Yuan, D and Zeng, X and Zhang, Y and Wu, Z}, title = {Diversity and Compatibility of Human Schistosomes and Their Intermediate Snail Hosts.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {493-510}, doi = {10.1016/j.pt.2018.03.004}, pmid = {29627269}, issn = {1471-5007}, abstract = {Human schistosomiasis is a major neglected tropical disease that remains endemic in numerous countries of the tropics and subtropics. Controlling the transmission of schistosomes in their intermediate snail hosts remains a key challenge in the fight against schistosomiasis. Divergence in species, biogeography, and genotype in schistosomes and their intermediate hosts has resulted in diverse parasite-host interactions. This review focuses on recent insights in the biogeography and diversity of schistosome species and their snail hosts, and the molecular basis of compatibility polymorphism between them.}, } @article {pmid29627203, year = {2018}, author = {King, AJ and Fehlmann, G and Biro, D and Ward, AJ and Fürtbauer, I}, title = {Re-wilding Collective Behaviour: An Ecological Perspective.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {347-357}, doi = {10.1016/j.tree.2018.03.004}, pmid = {29627203}, issn = {1872-8383}, mesh = {Animals ; Behavior, Animal ; Ecology/instrumentation/*methods ; Ethology/instrumentation/*methods ; *Social Behavior ; Vertebrates/*physiology ; }, abstract = {The earliest studies of collective animal behaviour were inspired by and conducted in the wild. Over the past decades much of the research in this field has shifted to the laboratory, combining high-resolution tracking of individuals with mathematical simulations or agent-based models. Today we are beginning to see a 're-wilding' of collective behaviour thanks to technological advances, providing researchers with the opportunity to quantify and model the heterogeneity that exists within the social groupings they study and within the environments in which these groups live. The perspective we present here aims to inspire and steer this research toward answering fundamental and outstanding behavioural and ecological questions, while also tackling pertinent conservation challenges.}, } @article {pmid29626666, year = {2018}, author = {Gilbert, PS and Wu, J and Simon, MW and Sinsheimer, JS and Alfaro, ME}, title = {Filtering nucleotide sites by phylogenetic signal to noise ratio increases confidence in the Neoaves phylogeny generated from ultraconserved elements.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {116-128}, pmid = {29626666}, issn = {1095-9513}, support = {R01 GM053275/GM/NIGMS NIH HHS/United States ; R01 GM086887/GM/NIGMS NIH HHS/United States ; T32 HG002536/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Birds/*classification/*genetics ; Nucleotides/*genetics ; *Phylogeny ; Regulatory Sequences, Nucleic Acid/genetics ; *Signal-To-Noise Ratio ; }, abstract = {Despite genome scale analyses, high-level relationships among Neoaves birds remain contentious. The placements of the Neoaves superorders are notoriously difficult to resolve because they involve deep splits followed by short internodes. Using our approach, we investigate whether filtering UCE loci on their phylogenetic signal to noise ratio helps to resolve key nodes in the Neoaves tree of life. We find that our analysis of data sets filtered for high signal to noise ratio results in topologies that are inconsistent with unfiltered results but that are congruent with whole-genome analyses. These relationships include the Columbea + Passerea sister relationship and the Phaethontimorphae + Aequornithia sister relationship. We also find increased statistical support for more recent nodes (i.e. the Pelecanidae + Ardeidae sister relationship, the Eucavitaves clade, and the Otidiformes + Musophagiformes sister relationship). We also find instances where support is reduced for well-established clades, possibly due to the removal of sites with moderate signal-to-noise ratio. Our results suggest that filtering on the basis of signal to noise ratio is a useful tool for resolving problematic splits in phylogenomic data sets.}, } @article {pmid29626665, year = {2018}, author = {Šumbera, R and Krásová, J and Lavrenchenko, LA and Mengistu, S and Bekele, A and Mikula, O and Bryja, J}, title = {Ethiopian highlands as a cradle of the African fossorial root-rats (genus Tachyoryctes), the genetic evidence.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {105-115}, doi = {10.1016/j.ympev.2018.04.003}, pmid = {29626665}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; *Ecosystem ; Ethiopia ; Geography ; Phylogeny ; Rodentia/*genetics ; Species Specificity ; Time Factors ; }, abstract = {Root-rats of the genus Tachyoryctes (Spalacidae) are subterranean herbivores occupying open humid habitats in the highlands of Eastern Africa. There is strong disagreement about species diversity of the genus, because some authors accept two species, while others more than ten. Species with relatively high surface activity, the giant root-rat Tachyoryctes macrocephalus, which is by far largest member of the genus, and the more fossorial African root-rat Tachyoryctes splendens, which eventually has been divided up to 12-13 species, represent two major morphological forms within the genus. In our study, we carried out a multilocus analysis of root-rats' genetic diversity based on samples from 41 localities representing most of Tachyoryctes geographic distribution. Using two mitochondrial and three nuclear genes, we found six main genetic clades possibly representing separate species. These clades were organised into three basal groups whose branching is not well resolved, probably due to fast radiation in the late Pliocene and early Pleistocene. Climatic changes in that time, i.e. fast and repeated changes between extremely dry and humid conditions, which both limited root-rat dispersal, probably stimulated their initial genetic diversification. Contrary to expectation based on the largest root-rat diversity in Kenya (up to eight species by some authors), we found the highest diversity in the Ethiopian highlands, because all but one putative species occur there. All individuals outside of Ethiopia belong to a single recently diverged and expanded clade. This species should bear the name T. annectens (Thomas, 1891), and all other names of taxa described from outside of Ethiopia should be considered its junior synonyms. However, to solve taxonomic issues, future detailed morphological analyses should be conducted on all main clades together with genetic analysis of material from areas of their supposed contact. One of the most interesting findings of the study is the internal position of T. macrocephalus in T. splendens sensu lato. This demonstrates the intriguing phenomenon of accelerated morphological evolution of rodents occupying the Afroalpine zone in Ethiopia. Finally, we discuss how the distribution of Tachyoryctes is influenced by competition with another group of subterranean herbivores on the continent, the African mole-rats. We assume that both groups do not compete directly as previously expected, but specialisation to different subterranean niches is the main factor responsible for their spatial segregation.}, } @article {pmid29626385, year = {2018}, author = {Webster, NS and Wagner, M and Negri, AP}, title = {Microbial conservation in the Anthropocene.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14124}, pmid = {29626385}, issn = {1462-2920}, } @article {pmid29626380, year = {2018}, author = {Tamayo, E and Knight, SAB and Valderas, A and Dancis, A and Ferrol, N}, title = {The arbuscular mycorrhizal fungus Rhizophagus irregularis uses a reductive iron assimilation pathway for high-affinity iron uptake.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1857-1872}, doi = {10.1111/1462-2920.14121}, pmid = {29626380}, issn = {1462-2920}, abstract = {Arbuscular mycorrhizal (AM) fungi can improve iron (Fe) acquisition of their host plants. Here, we report a characterization of two components of the high-affinity reductive Fe uptake system of Rhizophagus irregularis, the ferric reductase (RiFRE1) and the high affinity Fe permeases (RiFTR1-2). In the extraradical mycelia (ERM), Fe deficiency induced activation of a plasma membrane-localized ferric reductase, an enzyme that reduces Fe(III) sources to the more soluble Fe(II). Yeast mutant complementation assays showed that RiFRE1 encodes a functional ferric reductase and RiFTR1 an iron permease. In the heterologous system, RiFTR1 was expressed in the plasma membrane while RiFTR2 was expressed in the endomembranes. In the ERM, the highest expression levels of RiFTR1 were found in mycelia grown in media with 0.045 mM Fe, while RiFTR2 was upregulated under Fe-deficient conditions. RiFTR2 expression also increased in the intraradical mycelia (IRM) of maize plants grown without Fe. These data indicate that the Fe permease RiFTR1 plays a key role in Fe acquisition and that RiFTR2 is involved in Fe homeostasis under Fe-limiting conditions. RiFTR1 was highly expressed in the (IRM), which suggests that the maintenance of Fe homeostasis in the IRM might be essential for a successful symbiosis.}, } @article {pmid29626379, year = {2018}, author = {Carini, P and Dupont, CL and Santoro, AE}, title = {Patterns of thaumarchaeal gene expression in culture and diverse marine environments.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14107}, pmid = {29626379}, issn = {1462-2920}, abstract = {Thaumarchaea are ubiquitous in marine habitats where they participate in carbon and nitrogen cycling. Although metatranscriptomes suggest thaumarchaea are active microbes in marine waters, we understand little about how thaumarchaeal gene expression patterns relate to substrate utilization and activity. Here, we report the global transcriptional response of the marine ammonia-oxidizing thaumarchaeon 'Candidatus Nitrosopelagicus brevis' str. CN25 to ammonia limitation using RNA-Seq. We further describe the genome and transcriptome of Ca. N. brevis str. U25, a new strain capable of urea utilization. Ammonia limitation in CN25 resulted in reduced expression of transcripts coding for ammonia oxidation proteins, and increased expression of a gene coding an Hsp20-like chaperone. Despite significantly different transcript abundances across treatments, two ammonia monooxygenase subunits (amoAB), a nitrite reductase (nirK) and both ammonium transporter genes were always among the most abundant transcripts, regardless of growth state. Ca. N. brevis str. U25 cells expressed a urea transporter 139-fold more than the urease catalytic subunit ureC. Gene coexpression networks derived from culture transcriptomes and 10 thaumarchaea-enriched metatranscriptomes revealed a high degree of correlated gene expression across disparate environmental conditions and identified a module of coexpressed genes, including amoABC and nirK, that we hypothesize to represent the core ammonia oxidation machinery.}, } @article {pmid29626371, year = {2018}, author = {Baumgardner, K and Lin, C and Firtel, RA and Lacal, J}, title = {Phosphodiesterase PdeD, dynacortin, and a Kelch repeat-containing protein are direct GSK3 substrates in Dictyostelium that contribute to chemotaxis towards cAMP.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1888-1903}, doi = {10.1111/1462-2920.14126}, pmid = {29626371}, issn = {1462-2920}, abstract = {The migration of cells according to a diffusible chemical signal in their environment is called chemotaxis, and the slime mold Dictyostelium discoideum is widely used for the study of eukaryotic chemotaxis. Dictyostelium must sense chemicals, such as cAMP, secreted during starvation to move towards the sources of the signal. Previous work demonstrated that the gskA gene encodes the Dictyostelium homologue of glycogen synthase kinase 3 (GSK3), a highly conserved serine/threonine kinase, which plays a major role in the regulation of Dictyostelium chemotaxis. Cells lacking the GskA substrates Daydreamer and GflB exhibited chemotaxis defects less severe than those exhibited by gskA- (GskA null) cells, suggesting that additional GskA substrates might be involved in chemotaxis. Using phosphoproteomics we identify the GskA substrates PdeD, dynacortin and SogA and characterize the phenotypes of their respective null cells in response to the chemoattractant cAMP. All three chemotaxis phenotypes are defective, and in addition, we determine that carboxylesterase D2 is a common downstream effector of GskA, its direct substrates PdeD, GflB and the kinases GlkA and YakA, and that it also contributes to cell migration. Our findings identify new GskA substrates in cAMP signalling and break down the essential role of GskA in myosin II regulation.}, } @article {pmid29626370, year = {2018}, author = {Brüssow, H}, title = {Environmental microbiology: Too much food for thought? - An argument for reductionism.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14125}, pmid = {29626370}, issn = {1462-2920}, } @article {pmid29626347, year = {2018}, author = {Xu, L and Etienne, RS}, title = {Detecting local diversity-dependence in diversification.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1294-1305}, pmid = {29626347}, issn = {1558-5646}, abstract = {Whether there are ecological limits to species diversification is a hotly debated topic. Molecular phylogenies show slowdowns in lineage accumulation, suggesting that speciation rates decline with increasing diversity. A maximum-likelihood (ML) method to detect diversity-dependent (DD) diversification from phylogenetic branching times exists, but it assumes that diversity-dependence is a global phenomenon and therefore ignores that the underlying species interactions are mostly local, and not all species in the phylogeny co-occur locally. Here, we explore whether this ML method based on the nonspatial diversity-dependence model can detect local diversity-dependence, by applying it to phylogenies, simulated with a spatial stochastic model of local DD speciation, extinction, and dispersal between two local communities. We find that type I errors (falsely detecting diversity-dependence) are low, and the power to detect diversity-dependence is high when dispersal rates are not too low. Interestingly, when dispersal is high the power to detect diversity-dependence is even higher than in the nonspatial model. Moreover, estimates of intrinsic speciation rate, extinction rate, and ecological limit strongly depend on dispersal rate. We conclude that the nonspatial DD approach can be used to detect diversity-dependence in clades of species that live in not too disconnected areas, but parameter estimates must be interpreted cautiously.}, } @article {pmid29626248, year = {2018}, author = {Li, Z and Zhang, Y and Wang, Y and Mei, R and Zhang, Y and Hashmi, MZ and Lin, H and Su, X}, title = {A New Approach of Rpf Addition to Explore Bacterial Consortium for Enhanced Phenol Degradation Under High Salinity Conditions.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1046-1054}, pmid = {29626248}, issn = {1432-0991}, support = {2017F30030//Special Fund for the Zhejiang Research Academy of Environmental Science/ ; 41701354//National Natural Science Foundation of China/ ; LQ17D010002//Natural Science Foundation of Zhejiang Province of China/ ; ZZ323205020516001108//Research Fund for the Doctoral Research of Key University/ ; }, mesh = {Bacillus/growth & development/*metabolism ; Bacterial Proteins/*metabolism ; Biodegradation, Environmental ; Corynebacterium/growth & development/*metabolism ; Cytokines/*metabolism ; Phenols/*metabolism ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sodium Chloride/analysis ; Waste Water/*chemistry ; }, abstract = {Only a small fraction of salt-tolerant phenol-degrading bacteria can be isolated by conventional plate separation methods, because most bacteria in nature are in a viable but non-culturable (VBNC) state. The aims of this study were to screen out more effective functional bacteria using resuscitation-promoting factor (Rpf), and to determine whether a mixed bacterial consortium possesses better phenol-degrading capabilities under high salinity conditions. The results indicated that three strains unique to treatment group with Rpf addition were obtained. A mixed bacterial consortium consisting of two high-efficient strains which belonged to genera Bacillus and Corynebacterium was capable of utilizing phenol as a sole source of carbon at high salinity. Complete degradation of 100 mg/L phenol at 2% NaCl concentration was achieved within 8 h. This study provides new insights into resuscitation of VBNC bacteria for enhanced treatment of phenol-laden saline wastewater.}, } @article {pmid29626210, year = {2018}, author = {Baggen, J and Thibaut, HJ and Strating, JRPM and van Kuppeveld, FJM}, title = {The life cycle of non-polio enteroviruses and how to target it.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {368-381}, doi = {10.1038/s41579-018-0005-4}, pmid = {29626210}, issn = {1740-1534}, abstract = {The genus Enterovirus (EV) of the family Picornaviridae includes poliovirus, coxsackieviruses, echoviruses, numbered enteroviruses and rhinoviruses. These diverse viruses cause a variety of diseases, including non-specific febrile illness, hand-foot-and-mouth disease, neonatal sepsis-like disease, encephalitis, paralysis and respiratory diseases. In recent years, several non-polio enteroviruses (NPEVs) have emerged as serious public health concerns. These include EV-A71, which has caused epidemics of hand-foot-and-mouth disease in Southeast Asia, and EV-D68, which recently caused a large outbreak of severe lower respiratory tract disease in North America. Infections with these viruses are associated with severe neurological complications. For decades, most research has focused on poliovirus, but in recent years, our knowledge of NPEVs has increased considerably. In this Review, we summarize recent insights from enterovirus research with a special emphasis on NPEVs. We discuss virion structures, host-receptor interactions, viral uncoating and the recent discovery of a universal enterovirus host factor that is involved in viral genome release. Moreover, we briefly explain the mechanisms of viral genome replication, virion assembly and virion release, and describe potential targets for antiviral therapy. We reflect on how these recent discoveries may help the development of antiviral therapies and vaccines.}, } @article {pmid29626206, year = {2018}, author = {Brown, SDM and Holmes, CC and Mallon, AM and Meehan, TF and Smedley, D and Wells, S}, title = {High-throughput mouse phenomics for characterizing mammalian gene function.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {357-370}, doi = {10.1038/s41576-018-0005-2}, pmid = {29626206}, issn = {1471-0064}, support = {UM1 HG006370/HG/NHGRI NIH HHS/United States ; }, abstract = {We are entering a new era of mouse phenomics, driven by large-scale and economical generation of mouse mutants coupled with increasingly sophisticated and comprehensive phenotyping. These studies are generating large, multidimensional gene-phenotype data sets, which are shedding new light on the mammalian genome landscape and revealing many hitherto unknown features of mammalian gene function. Moreover, these phenome resources provide a wealth of disease models and can be integrated with human genomics data as a powerful approach for the interpretation of human genetic variation and its relationship to disease. In the future, the development of novel phenotyping platforms allied to improved computational approaches, including machine learning, for the analysis of phenotype data will continue to enhance our ability to develop a comprehensive and powerful model of mammalian gene-phenotype space.}, } @article {pmid29626132, year = {2018}, author = {Carr, JA and Franke, D and Caram, JR and Perkinson, CF and Saif, M and Askoxylakis, V and Datta, M and Fukumura, D and Jain, RK and Bawendi, MG and Bruns, OT}, title = {Shortwave infrared fluorescence imaging with the clinically approved near-infrared dye indocyanine green.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4465-4470}, pmid = {29626132}, issn = {1091-6490}, support = {R01 CA126642/CA/NCI NIH HHS/United States ; F31 HL126449/HL/NHLBI NIH HHS/United States ; U01 CA224348/CA/NCI NIH HHS/United States ; R35 CA197743/CA/NCI NIH HHS/United States ; P01 CA080124/CA/NCI NIH HHS/United States ; R01 CA208205/CA/NCI NIH HHS/United States ; R01 CA096915/CA/NCI NIH HHS/United States ; P41 EB015871/EB/NIBIB NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Blood Vessels/*diagnostic imaging ; Cattle ; *Contrast Media/pharmacokinetics/pharmacology ; *Fluorescent Dyes/pharmacokinetics/pharmacology ; Indocyanine Green ; *Infrared Rays ; Intravital Microscopy/*methods ; Lymphatic Vessels/*diagnostic imaging ; Mice ; Microscopy, Fluorescence/methods ; Trastuzumab/pharmacokinetics/pharmacology ; }, abstract = {Fluorescence imaging is a method of real-time molecular tracking in vivo that has enabled many clinical technologies. Imaging in the shortwave IR (SWIR; 1,000-2,000 nm) promises higher contrast, sensitivity, and penetration depths compared with conventional visible and near-IR (NIR) fluorescence imaging. However, adoption of SWIR imaging in clinical settings has been limited, partially due to the absence of US Food and Drug Administration (FDA)-approved fluorophores with peak emission in the SWIR. Here, we show that commercially available NIR dyes, including the FDA-approved contrast agent indocyanine green (ICG), exhibit optical properties suitable for in vivo SWIR fluorescence imaging. Even though their emission spectra peak in the NIR, these dyes outperform commercial SWIR fluorophores and can be imaged in the SWIR, even beyond 1,500 nm. We show real-time fluorescence imaging using ICG at clinically relevant doses, including intravital microscopy, noninvasive imaging in blood and lymph vessels, and imaging of hepatobiliary clearance, and show increased contrast compared with NIR fluorescence imaging. Furthermore, we show tumor-targeted SWIR imaging with IRDye 800CW-labeled trastuzumab, an NIR dye being tested in multiple clinical trials. Our findings suggest that high-contrast SWIR fluorescence imaging can be implemented alongside existing imaging modalities by switching the detection of conventional NIR fluorescence systems from silicon-based NIR cameras to emerging indium gallium arsenide-based SWIR cameras. Using ICG in particular opens the possibility of translating SWIR fluorescence imaging to human clinical applications. Indeed, our findings suggest that emerging SWIR-fluorescent in vivo contrast agents should be benchmarked against the SWIR emission of ICG in blood.}, } @article {pmid29626131, year = {2018}, author = {Starr, TN and Flynn, JM and Mishra, P and Bolon, DNA and Thornton, JW}, title = {Pervasive contingency and entrenchment in a billion years of Hsp90 evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4453-4458}, pmid = {29626131}, issn = {1091-6490}, support = {F32 GM119205/GM/NIGMS NIH HHS/United States ; R01 GM121931/GM/NIGMS NIH HHS/United States ; R01 GM112844/GM/NIGMS NIH HHS/United States ; R01 GM104397/GM/NIGMS NIH HHS/United States ; T32 GM007183/GM/NIGMS NIH HHS/United States ; }, mesh = {*Epistasis, Genetic ; *Evolution, Molecular ; *Gene Expression Regulation, Fungal ; HSP90 Heat-Shock Proteins/*genetics ; Protein Domains ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*genetics ; }, abstract = {Interactions among mutations within a protein have the potential to make molecular evolution contingent and irreversible, but the extent to which epistasis actually shaped historical evolutionary trajectories is unclear. To address this question, we experimentally measured how the fitness effects of historical sequence substitutions changed during the billion-year evolutionary history of the heat shock protein 90 (Hsp90) ATPase domain beginning from a deep eukaryotic ancestor to modern Saccharomyces cerevisiae We found a pervasive influence of epistasis. Of 98 derived amino acid states that evolved along this lineage, about half compromise fitness when introduced into the reconstructed ancestral Hsp90. And the vast majority of ancestral states reduce fitness when introduced into the extant S. cerevisiae Hsp90. Overall, more than 75% of historical substitutions were contingent on permissive substitutions that rendered the derived state nondeleterious, became entrenched by subsequent restrictive substitutions that made the ancestral state deleterious, or both. This epistasis was primarily caused by specific interactions among sites rather than a general effect on the protein's tolerance to mutation. Our results show that epistasis continually opened and closed windows of mutational opportunity over evolutionary timescales, producing histories and biological states that reflect the transient internal constraints imposed by the protein's fleeting sequence states.}, } @article {pmid29626130, year = {2018}, author = {Schiffer, PH and Polsky, AL and Cole, AG and Camps, JIR and Kroiher, M and Silver, DH and Grishkevich, V and Anavy, L and Koutsovoulos, G and Hashimshony, T and Yanai, I}, title = {The gene regulatory program of Acrobeloides nanus reveals conservation of phylum-specific expression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4459-4464}, pmid = {29626130}, issn = {1091-6490}, support = {322790//European Research Council/International ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Expression Regulation, Developmental/*physiology ; *Phylogeny ; Rhabditida/classification/*embryology/genetics ; Transcriptome/*physiology ; }, abstract = {The evolution of development has been studied through the lens of gene regulation by examining either closely related species or extremely distant animals of different phyla. In nematodes, detailed cell- and stage-specific expression analyses are focused on the model Caenorhabditis elegans, in part leading to the view that the developmental expression of gene cascades in this species is archetypic for the phylum. Here, we compared two species of an intermediate evolutionary distance: the nematodes C. elegans (clade V) and Acrobeloides nanus (clade IV). To examine A. nanus molecularly, we sequenced its genome and identified the expression profiles of all genes throughout embryogenesis. In comparison with C. elegans, A. nanus exhibits a much slower embryonic development and has a capacity for regulative compensation of missing early cells. We detected conserved stages between these species at the transcriptome level, as well as a prominent middevelopmental transition, at which point the two species converge in terms of their gene expression. Interestingly, we found that genes originating at the dawn of the Ecdysozoa supergroup show the least expression divergence between these two species. This led us to detect a correlation between the time of expression of a gene and its phylogenetic age: evolutionarily ancient and young genes are enriched for expression in early and late embryogenesis, respectively, whereas Ecdysozoa-specific genes are enriched for expression during the middevelopmental transition. Our results characterize the developmental constraints operating on each individual embryo in terms of developmental stages and genetic evolutionary history.}, } @article {pmid29626129, year = {2018}, author = {Sleczkowski, P and Zhou, Y and Iamsaard, S and de Pablo, JJ and Katsonis, N and Lacaze, E}, title = {Light-activated helical inversion in cholesteric liquid crystal microdroplets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4334-4339}, pmid = {29626129}, issn = {1091-6490}, abstract = {Cholesteric liquid crystal (CLC) droplets exhibit nontrivial topological features, which are controlled by the ratio between the cholesteric pitch and the droplet radius. The radial spherical structure (RSS) is of particular interest, as it reveals an onion-like concentric organization of the cholesteric helices, leading to the expression of spherical Bragg microcavities. Using an overcrowded alkene-based unidirectional molecular motor as a dopant, we show that the topological defect structure in the droplet can be activated by illumination. By using appropriate molecular motor concentrations, light can either break the symmetry of topological defects (as observed for the bent-twisted bipolar structure), or it can induce inversion of handedness in an onion-like organization (in the case of RSS). This latter feature may pave the way toward alternative activation modes of lasers based on cholesteric droplets. By also studying CLC droplets once they have reached full photoconversion at photostationary state (PSS), we highlight that the strong influence of confinement on the droplets structure occurs to the same extent after the helix inversion event. Our results are interpreted in terms of numerical simulations of the droplets' structure, which shed light on the major role played by curvature close to the droplets' center, this latter one becoming dominant when the droplet radius is small.}, } @article {pmid29625710, year = {2018}, author = {Alizon, S}, title = {Inexpensive Research in the Golden Open-Access Era.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {301-303}, doi = {10.1016/j.tree.2018.02.005}, pmid = {29625710}, issn = {1872-8383}, mesh = {*Access to Information ; Open Access Publishing/*economics/trends ; }, abstract = {The financial pressure that publishers impose on libraries is a worldwide concern. Gold open-access publishing with an expensive article-processing charge paid by the authors is often presented as an ideal solution to this problem. However, such a system threatens less-funded departments and even article quality.}, } @article {pmid29625591, year = {2018}, author = {Strehlau, R and van Aswegen, T and Potterton, J}, title = {Neurodevelopmental assessment of HIV-exposed uninfected and early-treated HIV-infected children: study protocol.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {235}, pmid = {29625591}, issn = {1756-0500}, mesh = {Anti-HIV Agents/administration & dosage/*pharmacology ; Child Development/*physiology ; Clinical Protocols ; Early Medical Intervention/*methods ; Female ; Follow-Up Studies ; HIV Infections/*drug therapy ; HIV Seropositivity/drug therapy ; Humans ; Infant ; Infant, Newborn ; Male ; Pregnancy ; *Pregnancy Complications, Infectious ; Prenatal Exposure Delayed Effects/*diagnosis/prevention & control ; South Africa ; }, abstract = {OBJECTIVE: Sub-Saharan Africa has the highest prevalence of children at risk of not achieving their developmental potential, attributable largely to the human immunodeficiency virus (HIV) pandemic coupled with negative environmental factors. Childhood developmental stimulation programmes can mitigate adverse outcomes.

METHODS: Neonates testing HIV positive at birth will be initiated on antiretroviral treatment (ART) and receive an age-appropriate stimulation program, updated at 3 monthly intervals through the first year of life. Neurodevelopment at 12 months of age will be assessed using the Bayley Scales of Infant and Toddler Development, Third Edition (BSID-III). Outcomes will be compared with HIV-infected and HIV-exposed uninfected children (HEU) not having received the stimulatory intervention. Associations between neurodevelopmental outcomes, environmental factors, and parental stress will be investigated. The study will take place at a single site in Johannesburg, South Africa. This non-randomised controlled intervention study, with a single non-blinded comparative intervention group, aims to investigate whether an early childhood stimulation programme used in conjunction with ART initiated at birth can positively impact neurodevelopmental outcomes at 1 year of age in children infected with HIV. Trial registration 15 January 2018, Pan African Clinical Trial Registry PACTR201801002967587.}, } @article {pmid29625561, year = {2018}, author = {Furmanová, K and Byška, J and Gröller, EM and Viola, I and Paleček, JJ and Kozlíková, B}, title = {COZOID: contact zone identifier for visual analysis of protein-protein interactions.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {125}, pmid = {29625561}, issn = {1471-2105}, support = {VRG11-010//Vienna Science and Technology Fund/International ; 218023//Norges Forskningsråd (NO)/International ; LQ1601//Ministerstvo Školství, Mládeže a Tělovýchovy/International ; MU/0822/2015//Grantová Agentura, Masarykova Univerzita (CZ)/International ; }, mesh = {Protein Interaction Domains and Motifs ; Protein Interaction Mapping/*methods ; Protein Structure, Tertiary ; Proteins/chemistry/*metabolism ; }, abstract = {BACKGROUND: Studying the patterns of protein-protein interactions (PPIs) is fundamental for understanding the structure and function of protein complexes. The exploration of the vast space of possible mutual configurations of interacting proteins and their contact zones is very time consuming and requires the proteomic expert knowledge.

RESULTS: In this paper, we propose a novel tool containing a set of visual abstraction techniques for the guided exploration of PPI configuration space. It helps proteomic experts to select the most relevant configurations and explore their contact zones at different levels of detail. The system integrates a set of methods that follow and support the workflow of proteomics experts. The first visual abstraction method, the Matrix view, is based on customized interactive heat maps and provides the users with an overview of all possible residue-residue contacts in all PPI configurations and their interactive filtering. In this step, the user can traverse all input PPI configurations and obtain an overview of their interacting amino acids. Then, the models containing a particular pair of interacting amino acids can be selectively picked and traversed. Detailed information on the individual amino acids in the contact zones and their properties is presented in the Contact-Zone list-view. The list-view provides a comparative tool to rank the best models based on the similarity of their contacts to the template-structure contacts. All these techniques are interactively linked with other proposed methods, the Exploded view and the Open-Book view, which represent individual configurations in three-dimensional space. These representations solve the high overlap problem associated with many configurations. Using these views, the structural alignment of the best models can also be visually confirmed.

CONCLUSIONS: We developed a system for the exploration of large sets of protein-protein complexes in a fast and intuitive way. The usefulness of our system has been tested and verified on several docking structures covering the three major types of PPIs, including coiled-coil, pocket-string, and surface-surface interactions. Our case studies prove that our tool helps to analyse and filter protein-protein complexes in a fraction of the time compared to using previously available techniques.}, } @article {pmid29625553, year = {2018}, author = {Hill, NS and Zuke, JD and Buske, PJ and Chien, AC and Levin, PA}, title = {A nutrient-dependent division antagonist is regulated post-translationally by the Clp proteases in Bacillus subtilis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {29}, pmid = {29625553}, issn = {1471-2180}, support = {R01 GM064671/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: Changes in nutrient availability have dramatic and well-defined impacts on both transcription and translation in bacterial cells. At the same time, the role of post-translational control in adaptation to nutrient-poor environments is poorly understood. Previous studies demonstrate the ability of the glucosyltransferase UgtP to influence cell size in response to nutrient availability. Under nutrient-rich medium, interactions with its substrate UDP-glucose promote interactions between UgtP and the tubulin-like cell division protein FtsZ in Bacillus subtilis, inhibiting maturation of the cytokinetic ring and increasing cell size. In nutrient-poor medium, reductions in UDP-glucose availability favor UgtP oligomerization, sequestering it from FtsZ and allowing division to occur at a smaller cell mass.

RESULTS: Intriguingly, in nutrient-poor conditions UgtP levels are reduced ~ 3-fold independent of UDP-glucose. B. subtilis cells cultured under different nutrient conditions indicate that UgtP accumulation is controlled through a nutrient-dependent post-translational mechanism dependent on the Clp proteases. Notably, all three B. subtilis Clp chaperones appeared able to target UgtP for degradation during growth in nutrient-poor conditions.

CONCLUSIONS: Together these findings highlight conditional proteolysis as a mechanism for bacterial adaptation to a rapidly changing nutritional landscape.}, } @article {pmid29625552, year = {2018}, author = {Gill, GP and Bryant, CJ and Fokin, M and Huege, J and Fraser, K and Jones, C and Cao, M and Faville, MJ}, title = {Low pyrrolizidine alkaloid levels in perennial ryegrass is associated with the absence of a homospermidine synthase gene.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {56}, pmid = {29625552}, issn = {1471-2229}, mesh = {Alkyl and Aryl Transferases/genetics/*metabolism ; Lolium/*enzymology/genetics/*metabolism ; Plant Breeding ; Pyrrolizidine Alkaloids/*metabolism ; }, abstract = {BACKGROUND: Pyrrolizidine alkaloids (PAs) are a class of secondary metabolites that function as feeding deterrents in a range of different plant species. In perennial ryegrass (Lolium perenne L.) the only PAs that have been identified are the thesinine-rhamnoside group, which displays significant genetic variation. Homospermidine synthase (HSS) has evolved from deoxyhypusine synthase (DHS) and catalyses the first step in the PA pathway, making it a key candidate for the investigation of genes influencing observed PA trait variation.

RESULTS: During PCR amplification and sequence analysis of DHS we identified two putative HSS genes in perennial ryegrass. One of the genes (LpHSS1) was absent in some perennial ryegrass plants. Thesinine-rhamnoside levels were measured using liquid chromatography coupled with mass spectrometry in a diverse association mapping population, consisting of 693 plants free of fungal endophytic symbionts. Association tests that accounted for population structure identified a significant association of absence of the LpHSS1 gene with lower levels of thesinine-rhamnoside PAs. HSS-like gene sequences were identified for other grass species of the Poaceae, including tall fescue, wheat, maize and sorghum.

CONCLUSION: HSS is situated at the crucial first step in the PA pathway making it an important candidate gene for investigation of involvement in PA phenotypic variation. In this study, PA level in perennial ryegrass was strongly associated with the presence or absence of the LpHSS1 gene. A genetic marker, developed for the presence/absence of LpHSS1, may be used for marker-assisted breeding to either lower or increase PAs in breeding populations of perennial or Italian ryegrass to investigate a potential role in the deterrence of herbivore pests. The presence of HSS-like genes in several other Poaceae species suggests that PA biosynthesis may occur in plant family members beyond perennial ryegrass and tall fescue and identifies a potential route for manipulating PA levels.}, } @article {pmid29625551, year = {2018}, author = {Najar, M and Crompot, E and van Grunsven, LA and Dollé, L and Lagneaux, L}, title = {Foreskin-derived mesenchymal stromal cells with aldehyde dehydrogenase activity: isolation and gene profiling.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {4}, pmid = {29625551}, issn = {1471-2121}, mesh = {Aldehyde Dehydrogenase/*metabolism ; Cell Cycle Proteins/genetics/metabolism ; Cell Hypoxia/genetics ; Cell Lineage ; Cell Separation/*methods ; Flow Cytometry ; Foreskin/*cytology ; *Gene Expression Profiling ; Humans ; Immunomodulation/genetics ; Immunophenotyping ; Male ; Mesenchymal Stem Cells/*cytology/*enzymology ; Neovascularization, Physiologic/genetics ; Phenotype ; }, abstract = {BACKGROUND: Mesenchymal stromal cells (MSCs) become an attractive research topic because of their crucial roles in tissue repair and regenerative medicine. Foreskin is considered as a valuable tissue source containing immunotherapeutic MSCs (FSK-MSCs).

RESULTS: In this work, we used aldehyde dehydrogenase activity (ALDH) assay (ALDEFLUOR™) to isolate and therefore characterize subsets of FSK-MSCs. According to their ALDH activity, we were able to distinguish and sort by fluorescence activated cell sorting (FACS) two subsets of FSK-MSCs (referred as ALDH+ and ALDH-). Consequently, these subsets were characterized by profiling the gene expression related to the main properties of MSCs (proliferation, response to hypoxia, angiogenesis, phenotype, stemness, multilineage, hematopoiesis and immunomodulation). We thus demonstrated by Real Time PCR several relevant differences in gene expression based on their ALDH activity.

CONCLUSION: Taken together, this preliminary study suggests that distinct subsets of FSK-MSCs with differential gene expression profiles depending of ALDH activity could be identified. These populations could differ in terms of biological functionalities involving the selection by ALDH activity as useful tool for potent therapeutic applications. However, functional studies should be conducted to confirm their therapeutic relevance.}, } @article {pmid29625550, year = {2018}, author = {Teixeira, MA and Rajewski, A and He, J and Castaneda, OG and Litt, A and Kaloshian, I}, title = {Classification and phylogenetic analyses of the Arabidopsis and tomato G-type lectin receptor kinases.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {239}, pmid = {29625550}, issn = {1471-2164}, support = {1461297//National Science Foundation (US)/ ; }, mesh = {Amino Acid Motifs ; Aquilegia/enzymology/genetics ; Arabidopsis/*enzymology/genetics ; Arabidopsis Proteins/chemistry/*classification/genetics/metabolism ; Catalytic Domain ; Chromosome Mapping ; Lycopersicon esculentum/*enzymology/genetics ; Multigene Family ; Oryza/enzymology/genetics ; Phylogeny ; Plant Proteins/chemistry/*classification/genetics/metabolism ; Protein Kinases/chemistry/*classification/genetics/metabolism ; Receptors, Cell Surface/chemistry/*classification/genetics/metabolism ; Terminology as Topic ; }, abstract = {BACKGROUND: Pathogen perception by plants is mediated by plasma membrane-localized immune receptors that have varied extracellular domains. Lectin receptor kinases (LecRKs) are among these receptors and are subdivided into 3 classes, C-type LecRKs (C-LecRKs), L-type LecRKs (L-LecRKs) and G-type LecRKs (G-LecRKs). While C-LecRKs are represented by one or two members in all plant species investigated and have unknown functions, L-LecRKs have been characterized in a few plant species and have been shown to play roles in plant defense against pathogens. Whereas Arabidopsis G-LecRKs have been characterized, this family of LecRKs has not been studied in tomato.

RESULTS: This investigation updates the current characterization of Arabidopsis G-LecRKs and characterizes the tomato G-LecRKs, using LecRKs from the monocot rice and the basal eudicot columbine to establish a basis for comparisons between the two core eudicots. Additionally, revisiting parameters established for Arabidopsis nomenclature for LecRKs is suggested for both Arabidopsis and tomato. Moreover, using phylogenetic analysis, we show the relationship among and between members of G-LecRKs from all three eudicot plant species. Furthermore, investigating presence of motifs in G-LecRKs we identified conserved motifs among members of G-LecRKs in tomato and Arabidopsis, with five present in at least 30 of the 38 Arabidopsis members and in at least 45 of the 73 tomato members.

CONCLUSIONS: This work characterized tomato G-LecRKs and added members to the currently characterized Arabidopsis G-LecRKs. Additionally, protein sequence analysis showed an expansion of this family in tomato as compared to Arabidopsis, and the existence of conserved common motifs in the two plant species as well as conserved species-specific motifs.}, } @article {pmid29625230, year = {2018}, author = {Garg, KM and Chattopadhyay, B and Wilton, PR and Malia Prawiradilaga, D and Rheindt, FE}, title = {Pleistocene land bridges act as semipermeable agents of avian gene flow in Wallacea.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {196-203}, doi = {10.1016/j.ympev.2018.03.032}, pmid = {29625230}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Birds/*genetics ; DNA, Mitochondrial/genetics ; *Gene Flow ; Genome ; Geography ; Islands ; Ochnaceae/genetics ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Principal Component Analysis ; Songbirds/genetics ; Time Factors ; }, abstract = {Cyclical periods of global cooling have been important drivers of biotic differentiation throughout the Quaternary. Ice age-induced sea level fluctuations can lead to changing patterns of land connections, both facilitating and disrupting gene flow. In this study, we test if species with differing life histories are differentially affected by Quaternary land connections. We used genome-wide SNPs in combination with mitochondrial gene sequences to analyse levels of divergence and gene flow between two songbird complexes across two Wallacean islands that have been repeatedly connected during glaciations. Although the two bird complexes are similar in ecological attributes, the forest and edge-inhabiting golden whistler Pachycephala pectoralis is comparatively flexible in its diet and niche requirements as compared to the henna-tailed jungle-flycatcher Cyornis colonus, which is largely restricted to the forest interior. Using population-genomic and coalescent approaches, we estimated levels of gene flow, population differentiation and divergence time between the two island populations. We observed higher levels of differentiation, an approximately two to four times deeper divergence time and near-zero levels of gene flow between the two island populations of the more forest-dependent henna-tailed jungle-flycatcher as compared to the more generalist golden whistler. Our results suggest that Quaternary land bridges act as semipermeable agents of gene flow in Wallacea, allowing only certain taxa to connect between islands while others remain isolated. Quaternary land bridges do not accommodate all terrestrial species equally, differing in suitability according to life history and species biology. More generalist species are likely to use Quaternary land connections as a conduit for gene flow between islands whereas island populations of more specialist species may continue to be reproductively isolated even during periods of Quaternary land bridges.}, } @article {pmid29625229, year = {2018}, author = {Alström, P and Cibois, A and Irestedt, M and Zuccon, D and Gelang, M and Fjeldså, J and Andersen, MJ and Moyle, RG and Pasquet, E and Olsson, U}, title = {Comprehensive molecular phylogeny of the grassbirds and allies (Locustellidae) reveals extensive non-monophyly of traditional genera, and a proposal for a new classification.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {367-375}, doi = {10.1016/j.ympev.2018.03.029}, pmid = {29625229}, issn = {1095-9513}, abstract = {The widespread Old World avian family Locustellidae ('grassbirds and allies') comprises 62 extant species in 11 genera. In the present study, we used one mitochondrial and, for most species, four nuclear loci to infer the phylogeny of this family. We analysed 59 species, including the five previously unsampled genera plus two genera that had not before been analysed in a densely sampled dataset. This study revealed extensive disagreement with current taxonomy; the genera Bradypterus, Locustella, Megalurus, Megalurulus and Schoenicola were all found to be non-monophyletic. Non-monophyly was particularly pronounced for Megalurus, which was widely scattered across the tree. Three of the five monotypic genera (Amphilais, Buettikoferella and Malia) were nested within other genera; one monotypic genus (Chaetornis) formed a clade with one of the two species of Schoenicola; whereas the position of the fifth monotypic genus (Elaphrornis) was unresolved. Robsonius was confirmed as sister to the other genera. We propose a phylogenetically informed revision of genus-level taxonomy, including one new generic name. Finally, we highlight several non-monophyletic species complexes and deep intra-species divergences that point to conflict in taxonomy and suggest an underestimation of current species diversity in this group.}, } @article {pmid29625228, year = {2018}, author = {Zhang, Y and Sun, J and Rouse, GW and Wiklund, H and Pleijel, F and Watanabe, HK and Chen, C and Qian, PY and Qiu, JW}, title = {Phylogeny, evolution and mitochondrial gene order rearrangement in scale worms (Aphroditiformia, Annelida).}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {220-231}, doi = {10.1016/j.ympev.2018.04.002}, pmid = {29625228}, issn = {1095-9513}, mesh = {Animals ; Annelida/*classification/*genetics ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; *Gene Order ; *Gene Rearrangement ; *Genes, Mitochondrial ; Genome, Mitochondrial ; Open Reading Frames/genetics ; *Phylogeny ; RNA, Ribosomal/genetics ; Sequence Analysis, DNA ; }, abstract = {Next-generation sequencing (NGS) has become a powerful tool in phylogenetic and evolutionary studies. Here we applied NGS to recover two ribosomal RNA genes (18S and 28S) from 16 species and 15 mitochondrial genomes from 16 species of scale worms representing six families in the suborder Aphroditiformia (Phyllodocida, Annelida), a complex group of polychaetes characterized by the presence of dorsal elytra or scales. The phylogenetic relationship of the several groups of scale worms remains unresolved due to insufficient taxon sampling and low resolution of individual gene markers. Phylogenetic tree topology based on mitochondrial genomes is comparable with that based on concatenated sequences from two mitochondrial genes (cox1 and 16S) and two ribosomal genes (18S and 28S) genes, but has higher statistical support for several clades. Our analyses show that Aphroditiformia is monophyletic, indicating the presence of elytra is an apomorphic trait. Eulepethidae and Aphroditidae together form the sister group to all other families in this suborder, whereas Acoetidae is sister to Iphionidae. Polynoidae is monophyletic, but within this family the deep-sea subfamilies Branchinotogluminae and Macellicephalinae are paraphyletic. Mitochondrial genomes in most scale-worm families have a conserved gene order, but within Polynoidae there are two novel arrangement patterns in the deep-sea clade. Mitochondrial protein-coding genes in polynoids as a whole have evolved under strong purifying selection, but substitution rates in deep-sea species are much higher than those in shallow-water species, indicating that purifying selection is relaxed in deep-sea polynoids. There are positive selected amino acids for some mitochondrial genes of the deep-sea clade, indicating they may involve in the adaption of deep-sea polynoids. Overall, our study (1) provided more evidence for reconstruction of the phylogeny of Aphroditiformia, (2) provided evidence to refute the assumption that mitochondrial gene order in Errantia is conserved, and (3) indicated that the deep-sea extreme environment may have affected the mitochondrial genome evolution rate and gene order arrangement in Polynoidae.}, } @article {pmid29624906, year = {2018}, author = {Popova, AA and Rasmussen, U and Semashko, TA and Govorun, VM and Koksharova, OA}, title = {Stress effects of cyanotoxin β-methylamino-L-alanine (BMAA) on cyanobacterial heterocyst formation and functionality.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {369-377}, doi = {10.1111/1758-2229.12647}, pmid = {29624906}, issn = {1758-2229}, abstract = {Various species of cyanobacteria, diatoms and dinoflagellates are capable of synthesizing the non-proteinogenic neurotoxic amino acid β-N-methylamino-L-alanine (BMAA), which is known to be a causative agent of human neurodegeneration. Similar to most cyanotoxins, the biological and ecological functions of BMAA in cyanobacteria are unknown. In this study, we show for the first time that BMAA, in micromolar amounts, inhibits the formation of heterocysts (specialized nitrogen-fixing cells) in heterocystous, diazotrophic cyanobacteria [Anabaena sp. PCC 7120, Nostoc punctiforme PCC 73102 (ATCC 29133), Nostoc sp. strain 8963] under conditions of nitrogen starvation. The inhibitory effect of BMAA is abolished by the addition of glutamate. To understand the genetic reason for the observed phenomenon, we used qPCR to study the expression of key genes involved in cell differentiation and nitrogen metabolism in the model cyanobacterium Anabaena sp. PCC 7120. We observed that in the presence of BMAA, Anabaena sp. PCC 7120 does not express two essential genes associated with heterocyst differentiation, namely, hetR and hepA. We also found that addition of BMAA to cyanobacterial cultures with mature heterocysts inhibits nifH gene expression and nitrogenase activity.}, } @article {pmid29624899, year = {2018}, author = {Sonnenschein, EC and Phippen, CBW and Bentzon-Tilia, M and Rasmussen, SA and Nielsen, KF and Gram, L}, title = {Phylogenetic distribution of roseobacticides in the Roseobacter group and their effect on microalgae.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {383-393}, doi = {10.1111/1758-2229.12649}, pmid = {29624899}, issn = {1758-2229}, abstract = {The Roseobacter-group species Phaeobacter inhibens produces the antibacterial tropodithietic acid (TDA) and the algaecidal roseobacticides with both compound classes sharing part of the same biosynthetic pathway. The purpose of this study was to investigate the production of roseobacticides more broadly in TDA-producing roseobacters and to compare the effect of producers and non-producers on microalgae. Of 33 roseobacters analyzed, roseobacticide production was a unique feature of TDA-producing P. inhibens, P. gallaeciensis and P. piscinae strains. One TDA-producing Phaeobacter, 27-4, did not produce roseobacticides, possibly due to a transposable element. TDA-producing Ruegeria and Pseudovibrio did not produce roseobacticides. Addition of roseobacticide-containing bacterial extracts affected the growth of the microalgae Rhodomonas salina, Thalassiosira pseudonana and Emiliania huxleyi, while growth of Tetraselmis suecica was unaffected. During co-cultivation, growth of E. huxleyi was initially stimulated by the roseobacticide producer DSM 17395, while the subsequent decline in algal cell numbers during senescence was enhanced. Strain 27-4 that does not produce roseobacticides had no effect on algal growth. Both bacterial strains, DSM 17395 and 27-4, grew during co-cultivation presumably utilizing algal exudates. Furthermore, TDA-producing roseobacters have potential as probiotics in marine larviculture and it is promising that the live feed Tetraselmis was unaffected by roseobacticides-containing extracts.}, } @article {pmid29624889, year = {2018}, author = {Michał, B and Gagat, P and Jabłoński, S and Chilimoniuk, J and Gaworski, M and Mackiewicz, P and Marcin, Ł}, title = {PhyMet2 : a database and toolkit for phylogenetic and metabolic analyses of methanogens.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {378-382}, doi = {10.1111/1758-2229.12648}, pmid = {29624889}, issn = {1758-2229}, abstract = {The vast biodiversity of the microbial world and how little is known about it, has already been revealed by extensive metagenomics analyses. Our rudimentary knowledge of microbes stems from difficulties concerning their isolation and culture in laboratory conditions, which is necessary for describing their phenotype, among other things, for biotechnological purposes. An important component of the understudied ecosystems is methanogens, archaea producing a potent greenhouse-effect gas methane. Therefore, we created PhyMet2 , the first database that combines descriptions of methanogens and their culturing conditions with genetic information. The database contains a set of utilities that facilitate interactive data browsing, data comparison, phylogeny exploration and searching for sequence homologues. The most unique feature of the database is the web server MethanoGram, which can be used to significantly reduce the time and cost of searching for the optimal culturing conditions of methanogens by predicting them based on 16S RNA sequences. The database will aid many researchers in exploring the world of methanogens and their applications in biotechnological processes. PhyMet2 with the MethanoGram predictor is available at http://metanogen.biotech.uni.wroc.pl.}, } @article {pmid29624877, year = {2018}, author = {Ren, G and Ma, A and Zhang, Y and Deng, Y and Zheng, G and Zhuang, X and Zhuang, G and Fortin, D}, title = {Electron acceptors for anaerobic oxidation of methane drive microbial community structure and diversity in mud volcanoes.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2370-2385}, doi = {10.1111/1462-2920.14128}, pmid = {29624877}, issn = {1462-2920}, abstract = {Mud volcanoes (MVs) emit globally significant quantities of methane into the atmosphere, however, methane cycling in such environments is not yet fully understood, as the roles of microbes and their associated biogeochemical processes have been largely overlooked. Here, we used data from high-throughput sequencing of microbial 16S rRNA gene amplicons from six MVs in the Junggar Basin in northwest China to quantify patterns of diversity and characterize the community structure of archaea and bacteria. We found anaerobic methanotrophs and diverse sulfate- and iron-reducing microbes in all of the samples, and the diversity of both archaeal and bacterial communities was strongly linked to the concentrations of sulfate, iron and nitrate, which could act as electron acceptors in anaerobic oxidation of methane (AOM). The impacts of sulfate/iron/nitrate on AOM in the MVs were verified by microcosm experiments. Further, two representative MVs were selected to explore the microbial interactions based on phylogenetic molecular ecological networks. The sites showed distinct network structures, key species and microbial interactions, with more complex and numerous linkages between methane-cycling microbes and their partners being observed in the iron/sulfate-rich MV. These findings suggest that electron acceptors are important factors driving the structure of microbial communities in these methane-rich environments.}, } @article {pmid29624831, year = {2018}, author = {McGrosky, A}, title = {Biology by the Bay.}, journal = {Evolutionary anthropology}, volume = {27}, number = {2}, pages = {78-79}, doi = {10.1002/evan.21583}, pmid = {29624831}, issn = {1520-6505}, } @article {pmid29624668, year = {2018}, author = {Churchill, M and Geisler, JH and Beatty, BL and Goswami, A}, title = {Evolution of cranial telescoping in echolocating whales (Cetacea: Odontoceti).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1092-1108}, doi = {10.1111/evo.13480}, pmid = {29624668}, issn = {1558-5646}, abstract = {Odontocete (echolocating whale) skulls exhibit extreme posterior displacement and overlapping of facial bones, here referred to as retrograde cranial telescoping. To examine retrograde cranial telescoping across 40 million years of whale evolution, we collected 3D scans of whale skulls spanning odontocete evolution. We used a sliding semilandmark morphometric approach with Procrustes superimposition and PCA to capture and describe the morphological variation present in the facial region, followed by Ancestral Character State Reconstruction (ACSR) and evolutionary model fitting on significant components to determine how retrograde cranial telescoping evolved. The first PC score explains the majority of variation associated with telescoping and reflects the posterior migration of the external nares and premaxilla alongside expansion of the maxilla and frontal. The earliest diverging fossil odontocetes were found to exhibit a lesser degree of cranial telescoping than later diverging but contemporary whale taxa. Major shifts in PC scores and centroid size are identified at the base of Odontoceti, and early burst and punctuated equilibrium models best fit the evolution of retrograde telescoping. This indicates that the Oligocene was a period of unusually high diversity and evolution in whale skull morphology, with little subsequent evolution in telescoping.}, } @article {pmid29624665, year = {2018}, author = {Inostroza-Michael, O and Hernández, CE and Rodríguez-Serrano, E and Avaria-Llautureo, J and Rivadeneira, MM}, title = {Interspecific geographic range size-body size relationship and the diversification dynamics of Neotropical furnariid birds.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1124-1133}, doi = {10.1111/evo.13481}, pmid = {29624665}, issn = {1558-5646}, abstract = {Among the earliest macroecological patterns documented, is the range and body size relationship, characterized by a minimum geographic range size imposed by the species' body size. This boundary for the geographic range size increases linearly with body size and has been proposed to have implications in lineages evolution and conservation. Nevertheless, the macroevolutionary processes involved in the origin of this boundary and its consequences on lineage diversification have been poorly explored. We evaluate the macroevolutionary consequences of the difference (hereafter the distance) between the observed and the minimum range sizes required by the species' body size, to untangle its role on the diversification of a Neotropical species-rich bird clade using trait-dependent diversification models. We show that speciation rate is a positive hump-shaped function of the distance to the lower boundary. The species with highest and lowest distances to minimum range size had lower speciation rates, while species close to medium distances values had the highest speciation rates. Further, our results suggest that the distance to the minimum range size is a macroevolutionary constraint that affects the diversification process responsible for the origin of this macroecological pattern in a more complex way than previously envisioned.}, } @article {pmid29624166, year = {2018}, author = {Ludvigsen, J and Porcellato, D and Amdam, GV and Rudi, K}, title = {Addressing the diversity of the honeybee gut symbiont Gilliamella: description of Gilliamella apis sp. nov., isolated from the gut of honeybees (Apis mellifera).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1762-1770}, doi = {10.1099/ijsem.0.002749}, pmid = {29624166}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Bees/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Gastrointestinal Tract/*microbiology ; Norway ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Symbiosis ; Ubiquinone/chemistry ; }, abstract = {The gut microbiota of honeybees (Apis) and bumblebees (Bombus) include the symbiotic bacterial genus Gilliamella. This genus shows a high degree of functional and genomic diversity and separates into distinct lineages. Gilliamella apicola wkB1T, which was isolated from Apis, was the first species to be described. Recently four new species, isolated from Bombus, were identified. In this paper, we compare several genomes/strains from previous studies spanning this diversity, which gives insight into the phylogenetic relationship among different Gilliamella species. We show that one lineage, isolated only from Apis, is different from other gilliamellas described, based on average nucleotide identity calculation (about 80 %) and phenotypic characterizations. We propose the new species name for this lineage: Gilliamella apis sp. nov. We present the characterization of the type strain NO3T (=DSM 105629T=LMG 30293T), a strain isolated from the Western honeybee Apis mellifera, which clusters within this lineage. Cells of strain NO3T grow best in a microaerophilic atmosphere with enhanced CO2 levels at 36 °C and pH 7.0-7.5. Cells also grow well in anaerobic conditions, but not in aerobic conditions. Cells are approximately 1 µm in length and rod-shaped, and the genomic G+C content is 34.7 mol%. Differential characteristics between strain NO3T and the different type strains of Gilliamella were revealed based on API kit tests and genomic content comparisons. The main respiratory quinone of strain NO3T was ubiquinone-8, and the predominant fatty acids were C18 : 1ω7c/C18 : 1ω6c, C16 : 0, consistent with the genus Gilliamella.}, } @article {pmid29624164, year = {2018}, author = {Gilbert, MJ and Zomer, AL and Timmerman, AJ and Spaninks, MP and Rubio-García, A and Rossen, JW and Duim, B and Wagenaar, JA}, title = {Campylobacter blaseri sp. nov., isolated from common seals (Phoca vitulina).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1787-1794}, doi = {10.1099/ijsem.0.002742}, pmid = {29624164}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Campylobacter/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Feces/microbiology ; Genes, Bacterial ; Netherlands ; Phenotype ; Phoca/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {During a study to assess the faecal microbiome of common seals (Phoca vitulina) in a Dutch seal rehabilitation centre, 16S rRNA gene sequences of an unknown Campylobacter taxon were identified. Campylobacter isolates, which differed from the established Campylobacter taxa, were cultured and their taxonomic position was determined by a polyphasic study based on ten isolates. The isolates were characterized by 16S rRNA and atpA gene sequence analyses and by conventional phenotypic testing. Based on the whole genome sequences, the average nucleotide identity and core genome phylogeny were determined. The isolates formed a separate phylogenetic clade, divergent from all other Campylobacter taxa and most closely related to Campylobacter corcagiensis, Campylobacter geochelonis and Campylobacter ureolyticus. The isolates can be distinguished phenotypically from all other Campylobacter taxa based on their lack of motility, growth at 25 °C and growth on MacConkey agar. This study shows that these isolates represent a novel species within the genus Campylobacter, for which the name Campylobacter blaseri sp. nov. is proposed. The type strain for this novel species is 17S00004-5T (=LMG 30333T=CCUG 71276T).}, } @article {pmid29624162, year = {2018}, author = {Také, A and Inahashi, Y and Ōmura, S and Takahashi, Y and Matsumoto, A}, title = {Streptomyces boninensis sp. nov., isolated from soil from a limestone cave in the Ogasawara Islands.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1795-1799}, doi = {10.1099/ijsem.0.002753}, pmid = {29624162}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; *Calcium Carbonate ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; *Islands ; Japan ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Actinomycete strain K11-0400T was isolated from a soil sample collected in the Ogasawara Islands (also known as the Bonin Islands), Tokyo, Japan. Mature spore chains of strain K11-0400T had more than 20 spores per chain. The strain contained ll-diaminopimelic acid as the diamino acid in whole-cell hydrolysates, and MK-9(H6) and MK-9(H4) were the predominant menaquinones. The polar lipids were phosphatidylethanolamine, diphosphatidylglycerol and phosphatidylinositol, and no diagnostic whole-cell sugar was detected. The G+C content of the genomic DNA was 72 mol%. These morphological and chemical features of strain K11-0400T indicated that it belonged to the genus Streptomyces. Strain K11-0400T showed the highest 16S rRNA gene sequence similarity to Streptomyces naganishii NBRC 12892T (97.58 %). However, the DNA-DNA relatedness value between strain K11-0400T and the related strain was below 70 %. Based on morphological, cultural and physiological characteristics, and DNA-DNA relatedness data, strain K11-0400T should be classified as a new species of the genus Streptomyces, for which the name Streptomyces boninensis sp. nov. is proposed. The type strain of S. boninensis is K11-0400T (=NBRC 113073T, TBRC 7755T).}, } @article {pmid29624160, year = {2018}, author = {Ko, DJ and Kim, JS and Park, DS and Lee, DH and Heo, SY and Seo, JW and Kim, CH and Oh, BR}, title = {Tabrizicola fusiformis sp. nov., isolated from an industrial wastewater treatment plant.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1800-1805}, doi = {10.1099/ijsem.0.002760}, pmid = {29624160}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Waste Water ; }, abstract = {The translucent white-coloured, Gram-stain-negative, aerobic, non-motile, fusiform-shaped bacterium (designated strain SY72T) was isolated from waste-activated sludge. Optimal growth occurred at 30-37 °C and pH 6.0-7.0. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that the novel isolate belonged to the family Rhodobacteraceae of the class Alphaproteobacteria. Strain SY72T is closely related to Tabrizicola aquatica KCTC 23724T (97.8 % 16S rRNA gene sequence similarity) and Pseudorhodobacter aquaticus DC2N1-10T (96.4 %), respectively. DNA-DNA relatedness between strain SY72T and the closest phylogenetically related strain, Tabrizicola aquatica KCTC 23724T, was 18.0±0.7 %. In strain SY72T, the predominant respiratory quinone was ubiquinone Q-10, and the cellular fatty acids consisted mainly of C18 : 1ω7c and C18 : 1ω7c-11 methyl. The major polar lipids were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. Photoautotrophic and photoheterotrophic growth did not occur in strain SY72T. Furthermore, strain SY72T did not produce photosynthetic pigments or contain the photosynthetic genes pufL and pufM, by which it differed from the phototrophic species of the family Rhodobacteraceae. On the basis of distinct phenotypic and phylogenetic properties, strain SY72T represents a novel species of the genus Tabrizicola, for which the name Tabrizicola fusiformis sp. nov. is proposed. The type strain is SY72T (=KCTC 62105T=NBRC 113021T).}, } @article {pmid29623398, year = {2018}, author = {Zhang, Y and Chen, Q and Ji, J and Zhao, L and Zhang, L and Qiu, J and He, J}, title = {Complete Genome Sequence of Alcaligenes Faecalis Strain JQ135, a Bacterium Capable of Efficiently Degrading Nicotinic Acid.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1551-1554}, pmid = {29623398}, issn = {1432-0991}, support = {No. 31500082//National Natural Science Foundation of China/ ; No. 31600080//National Natural Science Foundation of China/ ; No. 2016M601826//China Postdoctoral Science Foundation/ ; No. 1601035A//Postdoctoral Foundation of Jiangsu Province/ ; 2016YFD0801102//State's Key Project of Research and Development Plan/ ; }, mesh = {Alcaligenes faecalis/*genetics ; Biodegradation, Environmental ; Genome, Bacterial/*genetics ; Niacin/*metabolism ; Sequence Analysis, DNA/methods ; Soil Microbiology ; Whole Genome Sequencing/methods ; }, abstract = {Nicotinic acid (NA), known as vitamin B3, is ubiquitous in nature and plays an important role in living organisms. The microbial catabolism of NA is highly diverse. However, the NA degradation by Alcaligenes faecalis strains has been poorly investigated. In this study, we report the complete genome sequence of A. faecalis JQ135 (4.08 Mbp) and several essential genes for NA degradation. This genome sequence will facilitate to elucidate the molecular metabolism of NA and advance the potential biotechnological applications of A. faecalis strains.}, } @article {pmid29623351, year = {2018}, author = {Koenig, M}, title = {Primitive Dark-Phase Cycle of Photosynthesis at the Origin of Life.}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {167-171}, pmid = {29623351}, issn = {1432-1432}, abstract = {Simple phosphorylation, isomerization, and aldolisation reactions starting from glyceraldehyde have the potential to lead to the synthesis of pre-ribonucleotide polymers through a primitive form of the Calvin cycle (dark phase of photosynthesis) involving the unusual formation of phospho-nonulose phosphate and phospho-deculose phosphate, as key intermediates. These reactions involve activated phosphates which are generated from schreibersite minerals, geochemically available in Hadean times.}, } @article {pmid29623350, year = {2018}, author = {Voskarides, K}, title = {Group Selection May Explain Cancer Predisposition and Other Human Traits' Evolution.}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {184-186}, pmid = {29623350}, issn = {1432-1432}, abstract = {Group selection is a matter of acute controversy among evolutionary biologists. The most well-publicized debate in this regard is that between Edward O. Wilson and Richard Dawkins. As is widely known, Edward O. Wilson is very excited about the idea of social selection and eusociality; by contrast Richard Dawkins favors the idea of gene selection. As is often the case, the truth is somewhere in the middle. Evolution is most likely a multilevel procedure, where selection forces act on genes, individuals, and groups. Here, I would like to emphasize that group selection may be a possible cause of increased genetic variation on DNA repair genes, subsequently this driving to high cancer incidence. Additionally, if group selection is indeed happening in humans, maybe this is the reason that few adaptive loci have been discovered in human genome, even though thousands of sequenced genomes exist today.}, } @article {pmid29622726, year = {2018}, author = {Li, P and Markson, JS and Wang, S and Chen, S and Vachharajani, V and Elowitz, MB}, title = {Morphogen gradient reconstitution reveals Hedgehog pathway design principles.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {543-548}, doi = {10.1126/science.aao0645}, pmid = {29622726}, issn = {1095-9203}, support = {K99 HD087532/HD/NICHD NIH HHS/United States ; F32 AR067103/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/genetics/*physiology ; Feedback, Physiological ; Hedgehog Proteins/*metabolism ; Metabolic Networks and Pathways ; Mice ; Models, Biological ; NIH 3T3 Cells ; Patched-1 Receptor/genetics/*metabolism ; Sequence Deletion ; Signal Transduction ; }, abstract = {In developing tissues, cells estimate their spatial position by sensing graded concentrations of diffusible signaling proteins called morphogens. Morphogen-sensing pathways exhibit diverse molecular architectures, whose roles in controlling patterning dynamics and precision have been unclear. In this work, combining cell-based in vitro gradient reconstitution, genetic rewiring, and mathematical modeling, we systematically analyzed the distinctive architectural features of the Sonic Hedgehog pathway. We found that the combination of double-negative regulatory logic and negative feedback through the PTCH receptor accelerates gradient formation and improves robustness to variation in the morphogen production rate compared with alternative designs. The ability to isolate morphogen patterning from concurrent developmental processes and to compare the patterning behaviors of alternative, rewired pathway architectures offers a powerful way to understand and engineer multicellular patterning.}, } @article {pmid29622725, year = {2018}, author = {Muhar, M and Ebert, A and Neumann, T and Umkehrer, C and Jude, J and Wieshofer, C and Rescheneder, P and Lipp, JJ and Herzog, VA and Reichholf, B and Cisneros, DA and Hoffmann, T and Schlapansky, MF and Bhat, P and von Haeseler, A and Köcher, T and Obenauf, AC and Popow, J and Ameres, SL and Zuber, J}, title = {SLAM-seq defines direct gene-regulatory functions of the BRD4-MYC axis.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {800-805}, doi = {10.1126/science.aao2793}, pmid = {29622725}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Antineoplastic Agents/*pharmacology/therapeutic use ; Dose-Response Relationship, Drug ; Gene Expression Regulation, Leukemic/*drug effects ; *Genes, Regulator ; Humans ; Leukemia, Myeloid/*drug therapy/genetics ; Molecular Targeted Therapy ; Nuclear Proteins/genetics/*metabolism ; Proteins/*antagonists & inhibitors ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; Purines/biosynthesis ; RNA, Messenger/biosynthesis/genetics ; Ribosomes/metabolism ; Sequence Analysis, RNA ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic ; }, abstract = {Defining direct targets of transcription factors and regulatory pathways is key to understanding their roles in physiology and disease. We combined SLAM-seq [thiol(SH)-linked alkylation for the metabolic sequencing of RNA], a method for direct quantification of newly synthesized messenger RNAs (mRNAs), with pharmacological and chemical-genetic perturbation in order to define regulatory functions of two transcriptional hubs in cancer, BRD4 and MYC, and to interrogate direct responses to BET bromodomain inhibitors (BETis). We found that BRD4 acts as general coactivator of RNA polymerase II-dependent transcription, which is broadly repressed upon high-dose BETi treatment. At doses triggering selective effects in leukemia, BETis deregulate a small set of hypersensitive targets including MYC. In contrast to BRD4, MYC primarily acts as a selective transcriptional activator controlling metabolic processes such as ribosome biogenesis and de novo purine synthesis. Our study establishes a simple and scalable strategy to identify direct transcriptional targets of any gene or pathway.}, } @article {pmid29622724, year = {2018}, author = {Park, J and Shrestha, R and Qiu, C and Kondo, A and Huang, S and Werth, M and Li, M and Barasch, J and Suszták, K}, title = {Single-cell transcriptomics of the mouse kidney reveals potential cellular targets of kidney disease.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {758-763}, pmid = {29622724}, issn = {1095-9203}, support = {DP3 DK108220/DK/NIDDK NIH HHS/United States ; R01 DK087635/DK/NIDDK NIH HHS/United States ; R01 DK092684/DK/NIDDK NIH HHS/United States ; R01 DK073462/DK/NIDDK NIH HHS/United States ; U54 DK104309/DK/NIDDK NIH HHS/United States ; UG3 DK114926/DK/NIDDK NIH HHS/United States ; R01 DK076077/DK/NIDDK NIH HHS/United States ; R01 DK105821/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Plasticity ; Cell Tracking/*methods ; Gene Expression Profiling/*methods ; Genetic Markers ; Humans ; Kidney Diseases/*genetics ; Kidney Tubules, Collecting/*cytology/*metabolism ; Mice ; Receptors, Notch/metabolism ; Sequence Analysis, RNA/methods ; Signal Transduction ; Single-Cell Analysis/*methods ; }, abstract = {Our understanding of kidney disease pathogenesis is limited by an incomplete molecular characterization of the cell types responsible for the organ's multiple homeostatic functions. To help fill this knowledge gap, we characterized 57,979 cells from healthy mouse kidneys by using unbiased single-cell RNA sequencing. On the basis of gene expression patterns, we infer that inherited kidney diseases that arise from distinct genetic mutations but share the same phenotypic manifestation originate from the same differentiated cell type. We also found that the collecting duct in kidneys of adult mice generates a spectrum of cell types through a newly identified transitional cell. Computational cell trajectory analysis and in vivo lineage tracing revealed that intercalated cells and principal cells undergo transitions mediated by the Notch signaling pathway. In mouse and human kidney disease, these transitions were shifted toward a principal cell fate and were associated with metabolic acidosis.}, } @article {pmid29622723, year = {2018}, author = {Proctor, RSJ and Davis, HJ and Phipps, RJ}, title = {Catalytic enantioselective Minisci-type addition to heteroarenes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {419-422}, doi = {10.1126/science.aar6376}, pmid = {29622723}, issn = {1095-9203}, abstract = {Basic heteroarenes are a ubiquitous feature of pharmaceuticals and bioactive molecules, and Minisci-type additions of radical nucleophiles are a leading method for their elaboration. Despite many Minisci-type protocols that result in the formation of stereocenters, exerting control over the absolute stereochemistry at these centers remains an unmet challenge. We report a process for addition of prochiral radicals, generated from amino acid derivatives, to pyridines and quinolines. Our method offers excellent control of both enantioselectivity and regioselectivity. An enantiopure chiral Brønsted acid catalyst serves both to activate the substrate and induce asymmetry, while an iridium photocatalyst mediates the required electron transfer processes. We anticipate that this method will expedite access to enantioenriched small-molecule building blocks bearing versatile basic heterocycles.}, } @article {pmid29622682, year = {2018}, author = {Yost, WA}, title = {Auditory motion parallax.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {3998-4000}, pmid = {29622682}, issn = {1091-6490}, support = {R01 DC015214/DC/NIDCD NIH HHS/United States ; }, mesh = {*Depth Perception ; Motion ; *Motion Perception ; }, } @article {pmid29622681, year = {2018}, author = {Gong, L and Liu, F and Xiong, Z and Qi, R and Luo, Z and Gong, X and Nie, Q and Sun, Q and Liu, YF and Qing, W and Wang, L and Zhang, L and Tang, X and Huang, S and Li, G and Ouyang, H and Xiang, M and Nguyen, QD and Liu, Y and Li, DW}, title = {Heterochromatin protects retinal pigment epithelium cells from oxidative damage by silencing p53 target genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3987-E3995}, pmid = {29622681}, issn = {1091-6490}, mesh = {Animals ; *Apoptosis ; *Gene Silencing ; Heterochromatin/genetics/*metabolism/pathology ; Mice ; Mice, Knockout ; *Oxidative Stress ; Retinal Pigment Epithelium/*metabolism/pathology ; Sumoylation ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Oxidative stress (OS)-induced retinal pigment epithelium (RPE) cell apoptosis is critically implicated in the pathogenesis of age-related macular degeneration (AMD), a leading cause of blindness in the elderly. Heterochromatin, a compact and transcriptional inert chromatin structure, has been recently shown to be dynamically regulated in response to stress stimuli. The functional mechanism of heterochromatin on OS exposure is unclear, however. Here we show that OS increases heterochromatin formation both in vivo and in vitro, which is essential for protecting RPE cells from oxidative damage. Mechanistically, OS-induced heterochromatin selectively accumulates at p53-regulated proapoptotic target promoters and inhibits their transcription. Furthermore, OS-induced desumoylation of p53 promotes p53-heterochromatin interaction and regulates p53 promoter selection, resulting in the locus-specific recruitment of heterochromatin and transcription repression. Together, our findings demonstrate a protective function of OS-induced heterochromatin formation in which p53 desumoylation-guided promoter selection and subsequent heterochromatin recruitment play a critical role. We propose that targeting heterochromatin provides a plausible therapeutic strategy for the treatment of AMD.}, } @article {pmid29622653, year = {2018}, author = {O'Loughlin, L}, title = {No one is an island.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {122}, doi = {10.1126/science.360.6384.122}, pmid = {29622653}, issn = {1095-9203}, } @article {pmid29622652, year = {2018}, author = {Decker, M and Leslie, J and Liu, Q and Ding, L}, title = {Hepatic thrombopoietin is required for bone marrow hematopoietic stem cell maintenance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {106-110}, pmid = {29622652}, issn = {1095-9203}, support = {F30 HL137323/HL/NHLBI NIH HHS/United States ; R01 HL132074/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Gene Deletion ; Gene Knock-In Techniques ; Hematopoietic Stem Cells/metabolism/*physiology ; Hepatocytes/*metabolism ; Liver/*metabolism ; Mice ; Mice, Mutant Strains ; Thrombopoietin/genetics/*physiology ; }, abstract = {Hematopoietic stem cell (HSC) maintenance depends on extrinsic cues. Currently, only local signals arising from the bone marrow niche have been shown to maintain HSCs. However, it is not known whether systemic factors also sustain HSCs. We assessed the physiological source of thrombopoietin (TPO), a key cytokine required for maintaining HSCs. Using TpoDsRed-CreER knock-in mice, we showed that TPO is expressed by hepatocytes but not by bone marrow cells. Deletion of Tpo from hematopoietic cells, osteoblasts, or bone marrow mesenchymal stromal cells does not affect HSC number or function. However, when Tpo is deleted from hepatocytes, bone marrow HSCs are depleted. Thus, a cross-organ factor, circulating TPO made in the liver by hepatocytes, is required for bone marrow HSC maintenance. Our results demonstrate that systemic factors, in addition to the local niche, are a critical extrinsic component for HSC maintenance.}, } @article {pmid29622651, year = {2018}, author = {Otsuki, L and Brand, AH}, title = {Cell cycle heterogeneity directs the timing of neural stem cell activation from quiescence.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {99-102}, doi = {10.1126/science.aan8795}, pmid = {29622651}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Cell Cycle ; Cell Cycle Proteins/*metabolism ; Drosophila Proteins/*metabolism ; Drosophila melanogaster/cytology/enzymology ; Insulin/metabolism ; Neural Stem Cells/*cytology/enzymology ; *Neurogenesis ; Protein Tyrosine Phosphatases/metabolism ; Protein-Serine-Threonine Kinases/*metabolism ; Proteolysis ; Proto-Oncogene Proteins c-akt/metabolism ; Regeneration ; Signal Transduction ; Time Factors ; }, abstract = {Quiescent stem cells in adult tissues can be activated for homeostasis or repair. Neural stem cells (NSCs) in Drosophila are reactivated from quiescence in response to nutrition by the insulin signaling pathway. It is widely accepted that quiescent stem cells are arrested in G0 In this study, however, we demonstrate that quiescent NSCs (qNSCs) are arrested in either G2 or G0 G2-G0 heterogeneity directs NSC behavior: G2 qNSCs reactivate before G0 qNSCs. In addition, we show that the evolutionarily conserved pseudokinase Tribbles (Trbl) induces G2 NSCs to enter quiescence by promoting degradation of Cdc25String and that it subsequently maintains quiescence by inhibiting Akt activation. Insulin signaling overrides repression of Akt and silences trbl transcription, allowing NSCs to exit quiescence. Our results have implications for identifying and manipulating quiescent stem cells for regenerative purposes.}, } @article {pmid29622650, year = {2018}, author = {Chen, K and Huang, X and Kan, SBJ and Zhang, RK and Arnold, FH}, title = {Enzymatic construction of highly strained carbocycles.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {71-75}, pmid = {29622650}, issn = {1095-9203}, support = {F32 GM125231/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biocatalysis ; Cyclopropanes/*chemical synthesis ; Directed Molecular Evolution ; Escherichia coli/*enzymology ; Hemeproteins/*chemistry/genetics ; }, abstract = {Small carbocycles are structurally rigid and possess high intrinsic energy due to their ring strain. These features lead to broad applications but also create challenges for their construction. We report the engineering of hemeproteins that catalyze the formation of chiral bicyclobutanes, one of the most strained four-membered systems, via successive carbene addition to unsaturated carbon-carbon bonds. Enzymes that produce cyclopropenes, putative intermediates to the bicyclobutanes, were also identified. These genetically encoded proteins are readily optimized by directed evolution, function in Escherichia coli, and act on structurally diverse substrates with high efficiency and selectivity, providing an effective route to many chiral strained structures. This biotransformation is easily performed at preparative scale, and the resulting strained carbocycles can be derivatized, opening myriad potential applications.}, } @article {pmid29622649, year = {2018}, author = {Tsai, H and Asadpour, R and Blancon, JC and Stoumpos, CC and Durand, O and Strzalka, JW and Chen, B and Verduzco, R and Ajayan, PM and Tretiak, S and Even, J and Alam, MA and Kanatzidis, MG and Nie, W and Mohite, AD}, title = {Light-induced lattice expansion leads to high-efficiency perovskite solar cells.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {67-70}, doi = {10.1126/science.aap8671}, pmid = {29622649}, issn = {1095-9203}, abstract = {Light-induced structural dynamics plays a vital role in the physical properties, device performance, and stability of hybrid perovskite-based optoelectronic devices. We report that continuous light illumination leads to a uniform lattice expansion in hybrid perovskite thin films, which is critical for obtaining high-efficiency photovoltaic devices. Correlated, in situ structural and device characterizations reveal that light-induced lattice expansion benefits the performances of a mixed-cation pure-halide planar device, boosting the power conversion efficiency from 18.5 to 20.5%. The lattice expansion leads to the relaxation of local lattice strain, which lowers the energetic barriers at the perovskite-contact interfaces, thus improving the open circuit voltage and fill factor. The light-induced lattice expansion did not compromise the stability of these high-efficiency photovoltaic devices under continuous operation at full-spectrum 1-sun (100 milliwatts per square centimeter) illumination for more than 1500 hours.}, } @article {pmid29622648, year = {2018}, author = {Houlton, BZ and Morford, SL and Dahlgren, RA}, title = {Convergent evidence for widespread rock nitrogen sources in Earth's surface environment.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {58-62}, doi = {10.1126/science.aan4399}, pmid = {29622648}, issn = {1095-9203}, abstract = {Nitrogen availability is a pivotal control on terrestrial carbon sequestration and global climate change. Historical and contemporary views assume that nitrogen enters Earth's land-surface ecosystems from the atmosphere. Here we demonstrate that bedrock is a nitrogen source that rivals atmospheric nitrogen inputs across major sectors of the global terrestrial environment. Evidence drawn from the planet's nitrogen balance, geochemical proxies, and our spatial weathering model reveal that ~19 to 31 teragrams of nitrogen are mobilized from near-surface rocks annually. About 11 to 18 teragrams of this nitrogen are chemically weathered in situ, thereby increasing the unmanaged (preindustrial) terrestrial nitrogen balance from 8 to 26%. These findings provide a global perspective to reconcile Earth's nitrogen budget, with implications for nutrient-driven controls over the terrestrial carbon sink.}, } @article {pmid29622647, year = {2018}, author = {Abe, H and Jitsuki, S and Nakajima, W and Murata, Y and Jitsuki-Takahashi, A and Katsuno, Y and Tada, H and Sano, A and Suyama, K and Mochizuki, N and Komori, T and Masuyama, H and Okuda, T and Goshima, Y and Higo, N and Takahashi, T}, title = {CRMP2-binding compound, edonerpic maleate, accelerates motor function recovery from brain damage.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {50-57}, doi = {10.1126/science.aao2300}, pmid = {29622647}, issn = {1095-9203}, mesh = {Animals ; Brain Injuries/*drug therapy ; Intercellular Signaling Peptides and Proteins/*metabolism ; Male ; Maleates/*metabolism/*pharmacology/therapeutic use ; Mice ; Mice, Knockout ; Mice, Mutant Strains ; Motor Cortex/*drug effects/injuries/physiopathology ; Nerve Tissue Proteins/*metabolism ; Neuronal Plasticity/drug effects ; *Neuroprotection ; Quality of Life ; Receptors, AMPA/metabolism ; Recovery of Function/*drug effects ; Stroke/complications/drug therapy ; Thiophenes/*metabolism/*pharmacology/therapeutic use ; }, abstract = {Brain damage such as stroke is a devastating neurological condition that may severely compromise patient quality of life. No effective medication-mediated intervention to accelerate rehabilitation has been established. We found that a small compound, edonerpic maleate, facilitated experience-driven synaptic glutamate AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole-propionic-acid) receptor delivery and resulted in the acceleration of motor function recovery after motor cortex cryoinjury in mice in a training-dependent manner through cortical reorganization. Edonerpic bound to collapsin-response-mediator-protein 2 (CRMP2) and failed to augment recovery in CRMP2-deficient mice. Edonerpic maleate enhanced motor function recovery from internal capsule hemorrhage in nonhuman primates. Thus, edonerpic maleate, a neural plasticity enhancer, could be a clinically potent small compound with which to accelerate rehabilitation after brain damage.}, } @article {pmid29622646, year = {2018}, author = {Singer, JD and Braun, HI}, title = {Testing international education assessments.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {38-40}, doi = {10.1126/science.aar4952}, pmid = {29622646}, issn = {1095-9203}, } @article {pmid29622645, year = {2018}, author = {Alessi, DR and Sammler, E}, title = {LRRK2 kinase in Parkinson's disease.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {36-37}, doi = {10.1126/science.aar5683}, pmid = {29622645}, issn = {1095-9203}, mesh = {Animals ; Communicable Diseases/complications/genetics ; Genes, Dominant ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*genetics/metabolism ; Mice ; Mutation, Missense ; Parkinson Disease/etiology/*genetics ; Phosphorylation ; Signal Transduction ; rab GTP-Binding Proteins/metabolism ; }, } @article {pmid29622644, year = {2018}, author = {Heldwein, EE}, title = {Up close with herpesviruses.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {34-35}, doi = {10.1126/science.aat3990}, pmid = {29622644}, issn = {1095-9203}, support = {R01 GM111795/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*DNA, Viral ; Herpesviridae/*genetics ; Herpesviridae Infections ; Humans ; }, } @article {pmid29622643, year = {2018}, author = {Gutierrez, MG and Carlton, JG}, title = {ESCRTs offer repair service.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {33-34}, doi = {10.1126/science.aat2630}, pmid = {29622643}, issn = {1095-9203}, mesh = {*Endosomal Sorting Complexes Required for Transport ; }, } @article {pmid29622642, year = {2018}, author = {Repellin, C and Regnault, N}, title = {Lattices for fractional Chern insulators.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {31-32}, doi = {10.1126/science.aar5675}, pmid = {29622642}, issn = {1095-9203}, mesh = {Electric Conductivity ; Magnets ; *Models, Chemical ; *Quantum Theory ; }, } @article {pmid29622641, year = {2018}, author = {Rumpel, S}, title = {Supporting recovery from brain injury.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {30-31}, doi = {10.1126/science.aat2450}, pmid = {29622641}, issn = {1095-9203}, mesh = {*Brain Injuries ; Humans ; *Recovery of Function ; }, } @article {pmid29622640, year = {2018}, author = {Rochman, CM}, title = {Microplastics research-from sink to source.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {28-29}, doi = {10.1126/science.aar7734}, pmid = {29622640}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; Fishes ; *Fresh Water ; Plastics/*toxicity ; Water Pollutants, Chemical/*toxicity ; *Water Pollution, Chemical ; }, } @article {pmid29622639, year = {2018}, author = {Brotherton, CA and Naz, S and Zaidi, SS and Dennis, AF and Hämäläinen, A and Strielkowski, W and Lyu, MA and Wenderott, JK and Espinosa-Diez, C and Isaacson, K and Li, Y and Hassan, E and Hoyer, JS and Cusimano, JM}, title = {NextGen VOICES: A postdoc's purpose.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {26-27}, doi = {10.1126/science.aat6008}, pmid = {29622639}, issn = {1095-9203}, } @article {pmid29622638, year = {2018}, author = {Kumar, S}, title = {A one-man fossil rescue mission.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {24}, doi = {10.1126/science.360.6384.24}, pmid = {29622638}, issn = {1095-9203}, mesh = {Animals ; *Dinosaurs ; *Fossils ; India ; *Ovum ; Risk ; }, } @article {pmid29622637, year = {2018}, author = {Kumar, S}, title = {Edge of extinction.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {22-25}, doi = {10.1126/science.360.6384.22}, pmid = {29622637}, issn = {1095-9203}, mesh = {Animals ; *Dinosaurs ; *Extinction, Biological ; *Fossils ; India ; }, } @article {pmid29622636, year = {2018}, author = {Broadfoot, M}, title = {A delicate balance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {18-20}, doi = {10.1126/science.360.6384.18}, pmid = {29622636}, issn = {1095-9203}, mesh = {Anti-Bacterial Agents/administration & dosage/*adverse effects ; Humans ; Infant ; Infant, Newborn ; *Infant, Premature ; Infection/diagnosis/drug therapy ; Microbiota/*drug effects ; Prescription Drug Overuse/*adverse effects ; }, } @article {pmid29622635, year = {2018}, author = {Brainard, J}, title = {NIH looks to punish reviewers who violate confidentiality.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {17}, doi = {10.1126/science.360.6384.17}, pmid = {29622635}, issn = {1095-9203}, mesh = {*Confidentiality ; National Institutes of Health (U.S.) ; Peer Review, Research/*legislation & jurisprudence ; *Punishment ; United States ; }, } @article {pmid29622634, year = {2018}, author = {Normile, D}, title = {Rocky start for China's James Watson center.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {16}, doi = {10.1126/science.360.6384.16}, pmid = {29622634}, issn = {1095-9203}, } @article {pmid29622633, year = {2018}, author = {Staaf, D}, title = {Humane studies of octopuses get a boost.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {14-15}, doi = {10.1126/science.360.6384.14}, pmid = {29622633}, issn = {1095-9203}, mesh = {Anesthetics/*pharmacology ; Animal Experimentation/*ethics ; *Animal Rights ; Animals ; Ethanol/administration & dosage ; Humanism ; Magnesium Chloride/pharmacology ; Neurosciences/*ethics ; Octopodiformes/*drug effects ; Pain/*prevention & control ; }, } @article {pmid29622632, year = {2018}, author = {McCook, A and , }, title = {University is quick to disclose misconduct.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {13-14}, doi = {10.1126/science.360.6384.13}, pmid = {29622632}, issn = {1095-9203}, } @article {pmid29622631, year = {2018}, author = {Mervis, J}, title = {In its second year, March for Science grows up.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {12-13}, doi = {10.1126/science.360.6384.12}, pmid = {29622631}, issn = {1095-9203}, } @article {pmid29622630, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {10-11}, doi = {10.1126/science.360.6384.10}, pmid = {29622630}, issn = {1095-9203}, } @article {pmid29622629, year = {2018}, author = {Maxon, ME and Alberts, B}, title = {Science for state legislatures.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {9}, doi = {10.1126/science.aat7661}, pmid = {29622629}, issn = {1095-9203}, } @article {pmid29622628, year = {2018}, author = {Dai, X and Zhou, ZH}, title = {Structure of the herpes simplex virus 1 capsid with associated tegument protein complexes.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {}, pmid = {29622628}, issn = {1095-9203}, support = {R01 CA187238/CA/NCI NIH HHS/United States ; R01 AI094386/AI/NIAID NIH HHS/United States ; S10 OD018111/OD/NIH HHS/United States ; U24 GM116792/GM/NIGMS NIH HHS/United States ; R01 GM071940/GM/NIGMS NIH HHS/United States ; R01 DE025567/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Capsid/*chemistry/ultrastructure ; Capsid Proteins/*chemistry/ultrastructure ; Cercopithecus aethiops ; Cryoelectron Microscopy ; Glycoproteins/chemistry/ultrastructure ; Herpesvirus 1, Human/*chemistry/ultrastructure ; Humans ; Protein Conformation, alpha-Helical ; Vero Cells ; }, abstract = {Herpes simplex viruses (HSVs) rely on capsid-associated tegument complex (CATC) for long-range axonal transport of their genome-containing capsids between sites of infection and neuronal cell bodies. Here we report cryo-electron microscopy structures of the HSV-1 capsid with CATC up to 3.5-angstrom resolution and atomic models of multiple conformers of capsid proteins VP5, VP19c, VP23, and VP26 and tegument proteins pUL17, pUL25, and pUL36. Crowning every capsid vertex are five copies of heteropentameric CATC, each containing a pUL17 monomer supporting the coiled-coil helix bundle of a pUL25 dimer and a pUL36 dimer, thus positioning their flexible domains for potential involvement in nuclear capsid egress and axonal capsid transport. Notwithstanding newly discovered fold conservation between triplex proteins and bacteriophage λ protein gpD and the previously recognized bacteriophage HK97 gp5-like fold in VP5, HSV-1 capsid proteins exhibit extraordinary diversity in forms of domain insertion and conformational polymorphism, not only for interactions with tegument proteins but also for encapsulation of large genomes.}, } @article {pmid29622627, year = {2018}, author = {Yuan, S and Wang, J and Zhu, D and Wang, N and Gao, Q and Chen, W and Tang, H and Wang, J and Zhang, X and Liu, H and Rao, Z and Wang, X}, title = {Cryo-EM structure of a herpesvirus capsid at 3.1 Å.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {}, doi = {10.1126/science.aao7283}, pmid = {29622627}, issn = {1095-9203}, mesh = {Capsid/*chemistry/ultrastructure ; Capsid Proteins/*chemistry/ultrastructure ; Cryoelectron Microscopy ; Herpesvirus 2, Human/*chemistry/ultrastructure ; Humans ; Image Processing, Computer-Assisted ; }, abstract = {Structurally and genetically, human herpesviruses are among the largest and most complex of viruses. Using cryo-electron microscopy (cryo-EM) with an optimized image reconstruction strategy, we report the herpes simplex virus type 2 (HSV-2) capsid structure at 3.1 angstroms, which is built up of about 3000 proteins organized into three types of hexons (central, peripentonal, and edge), pentons, and triplexes. Both hexons and pentons contain the major capsid protein, VP5; hexons also contain a small capsid protein, VP26; and triplexes comprise VP23 and VP19C. Acting as core organizers, VP5 proteins form extensive intermolecular networks, involving multiple disulfide bonds (about 1500 in total) and noncovalent interactions, with VP26 proteins and triplexes that underpin capsid stability and assembly. Conformational adaptations of these proteins induced by their microenvironments lead to 46 different conformers that assemble into a massive quasisymmetric shell, exemplifying the structural and functional complexity of HSV.}, } @article {pmid29622626, year = {2018}, author = {Skowyra, ML and Schlesinger, PH and Naismith, TV and Hanson, PI}, title = {Triggered recruitment of ESCRT machinery promotes endolysosomal repair.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {}, pmid = {29622626}, issn = {1095-9203}, support = {R01 GM122434/GM/NIGMS NIH HHS/United States ; }, mesh = {Calcium-Binding Proteins/genetics/metabolism ; Cell Cycle Proteins/genetics/metabolism ; Cell Line, Tumor ; DNA-Binding Proteins/genetics/metabolism ; Endosomal Sorting Complexes Required for Transport/genetics/*metabolism ; Endosomes/*metabolism ; HeLa Cells ; Humans ; Lysosomes/*metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {Endolysosomes can be damaged by diverse materials. Terminally damaged compartments are degraded by lysophagy, but pathways that repair salvageable organelles are poorly understood. Here we found that the endosomal sorting complex required for transport (ESCRT) machinery, known to mediate budding and fission on endolysosomes, also plays an essential role in their repair. ESCRTs were rapidly recruited to acutely injured endolysosomes through a pathway requiring calcium and ESCRT-activating factors that was independent of lysophagy. We used live-cell imaging to demonstrate that ESCRTs responded to small perforations in endolysosomal membranes and enabled compartments to recover from limited damage. Silica crystals that disrupted endolysosomes also triggered ESCRT recruitment. ESCRTs thus provide a defense against endolysosomal damage likely to be relevant in physiological and pathological contexts.}, } @article {pmid29622038, year = {2018}, author = {Choo, SM and Ban, B and Joo, JI and Cho, KH}, title = {The phenotype control kernel of a biomolecular regulatory network.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {49}, pmid = {29622038}, issn = {1752-0509}, support = {2017R1A2A1A17069642, 2015M3A9A7067220, and 2013M3A9A7046303//National Research Foundation of Korea/ ; KAIST Future Systems Healthcare Project//KAIST Future Systems Healthcare Project/ ; KUSTAR-KAIST Institute//KUSTAR-KAIST Institute/ ; HI13C2162//Korean Health Technology R&D Project/ ; }, abstract = {BACKGROUND: Controlling complex molecular regulatory networks is getting a growing attention as it can provide a systematic way of driving any cellular state to a desired cell phenotypic state. A number of recent studies suggested various control methods, but there is still deficiency in finding out practically useful control targets that ensure convergence of any initial network state to one of attractor states corresponding to a desired cell phenotype.

RESULTS: To find out practically useful control targets, we introduce a new concept of phenotype control kernel (PCK) for a Boolean network, defined as the collection of all minimal sets of control nodes having their fixed state values that can generate all possible control sets which eventually drive any initial state to one of attractor states corresponding to a particular cell phenotype of interest. We also present a detailed method with which we can identify PCK in a systematic way based on the layered network and converging tree of a given network. We identify all candidates for control nodes from the layered network and then hierarchically search for all possible minimal sets by using the converging tree. We show the usefulness of PCK by applying it to cell proliferation and apoptosis signaling networks and comparing the results with other control methods. PCK is the unique control method for Boolean network models that can be used to identify all possible minimal sets of control nodes. Interestingly, many of the minimal sets have only one or two control nodes.

CONCLUSIONS: Based on the new concept of PCK, we can identify all possible minimal sets of control nodes that can drive any molecular network state to one of multiple attractor states representing a same desired cell phenotype.}, } @article {pmid29622031, year = {2018}, author = {Aljadani, R and Aseeri, M}, title = {Prevalence of drug-drug interactions in geriatric patients at an ambulatory care pharmacy in a tertiary care teaching hospital.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {234}, pmid = {29622031}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Ambulatory Care ; Cross-Sectional Studies ; *Drug Interactions ; Drug Prescriptions/*statistics & numerical data ; Drug-Related Side Effects and Adverse Reactions/*epidemiology ; Female ; Hospitals, Teaching/*statistics & numerical data ; Humans ; Male ; Pharmacies/*statistics & numerical data ; Prevalence ; Retrospective Studies ; Saudi Arabia ; Tertiary Healthcare ; }, abstract = {OBJECTIVE: A cross-sectional study was performed from February to May 2015, to estimate the prevalence of drug-drug interactions in geriatric patients at the ambulatory care pharmacy at King Abdul-Aziz Medical City in Jeddah, Saudi Arabia.

RESULTS: A total of 310 patients were included, with a mean age (± SD) of 73.78 ± 6.96, and 48.70% were female. The overall prevalence of DDIs of all categories was 90.64%. Category B DDIs was 55.80%, category C DDIs 87.74%, category D DDIs 51.93%, and category X DDIs 16.45%. Atorvastatine plus omeprazole was identified as the most common interacting pair, with a prevalence of 25.26%. Multivariate logistic regression analysis showed that category D or X DDIs are more likely to occur in the female patient (OR = 1.79; 95% CI 1.07, 2.97), the patient taking more than three medications (OR = 22.62; 95% CI 2.93, 174.83), and the patient with more than two conditions (OR = 3.09; 95% CI 1.81, 5.27).}, } @article {pmid29622028, year = {2018}, author = {Sah, AK and Shrestha, N and Joshi, P and Lakha, R and Shrestha, S and Sharma, L and Chandra, A and Singh, N and Kc, Y and Rijal, B}, title = {Association of parental methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in couples with unexplained recurrent pregnancy loss.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {233}, pmid = {29622028}, issn = {1756-0500}, mesh = {Abortion, Habitual/*genetics ; Adult ; Cross-Sectional Studies ; Female ; Humans ; Male ; Methylenetetrahydrofolate Reductase (NADPH2)/*genetics ; Nepal ; Polymorphism, Genetic ; Pregnancy ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to identify the association of parental MTHFR C677T gene polymorphism in couples with and without RPL history.

RESULTS: During the study, 21.4% (15/70) of Ala222Val polymorphism was observed among RPL couples while no polymorphism was seen among normal, healthy couples. Our study did not find any association between MTHFR C677T polymorphism and gender (p > 0.05), gestational period (p > 0.05), geographical region (p > 0.05) and menstrual history (p > 0.05). However, significant association was seen between MTHFR C677T polymorphism and number of losses (p < 0.05), concluding that the risk of the polymorphism increased with the increase in number of losses. Significant variation in the MTHFR C677T genotype with number of losses among RPL couples were seen but not with other study variables.}, } @article {pmid29621997, year = {2018}, author = {Djanaguiraman, M and Boyle, DL and Welti, R and Jagadish, SVK and Prasad, PVV}, title = {Decreased photosynthetic rate under high temperature in wheat is due to lipid desaturation, oxidation, acylation, and damage of organelles.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {55}, pmid = {29621997}, issn = {1471-2229}, support = {P20 GM103418/GM/NIGMS NIH HHS/United States ; Triticeae-CAP-2011-68002-30029//National Institute of Food and Agriculture/International ; Grant no. AID-0AA-A-13-00008//United States Agency for International Development/International ; Sustainable Intensificatio Innovation Lab - Grant no. AID-0AA-L-14-00006//United States Agency for International Development/International ; }, mesh = {Hot Temperature ; Oxidation-Reduction ; Photosynthesis/genetics/*physiology ; Reactive Oxygen Species/metabolism ; Temperature ; Triglycerides/metabolism ; Triticum/genetics/*metabolism ; }, abstract = {BACKGROUND: High temperature is a major abiotic stress that limits wheat (Triticum aestivum L.) productivity. Variation in levels of a wide range of lipids, including stress-related molecular species, oxidative damage, cellular organization and ultrastructural changes were analyzed to provide an integrated view of the factors that underlie decreased photosynthetic rate under high temperature stress. Wheat plants of cultivar Chinese Spring were grown at optimum temperatures (25/15 °C, maximum/minimum) until the onset of the booting stage. Thereafter, plants were exposed to high temperature (35/25 °C) for 16 d.

RESULTS: Compared with optimum temperature, a lower photosynthetic rate was observed at high temperature which is an interplay between thylakoid membrane damage, thylakoid membrane lipid composition, oxidative damage of cell organelle, and stomatal and non-stomatal limitations. Triacylglycerol levels were higher under high temperature stress. Polar lipid fatty acyl unsaturation was lower at high temperature, while triacylglycerol unsaturation was the same at high temperature and optimum temperature. The changes in lipid species indicates increases in activities of desaturating, oxidizing, glycosylating and acylating enzymes under high temperature stress. Cumulative effect of high temperature stress led to generation of reactive oxygen species, cell organelle and membrane damage, and reduced antioxidant enzyme activity, and imbalance between reactive oxygen species and antioxidant defense system.

CONCLUSIONS: Taken together with recent findings demonstrating that reactive oxygen species are formed from and are removed by thylakoid lipids, the data suggest that reactive oxygen species production, reactive oxygen species removal, and changes in lipid metabolism contribute to decreased photosynthetic rate under high temperature stress.}, } @article {pmid29621980, year = {2018}, author = {Pace, RM and Prince, AL and Ma, J and Belfort, BDW and Harvey, AS and Hu, M and Baquero, K and Blundell, P and Takahashi, D and Dean, T and Kievit, P and Sullivan, EL and Friedman, JE and Grove, K and Aagaard, KM}, title = {Modulations in the offspring gut microbiome are refractory to postnatal synbiotic supplementation among juvenile primates.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {28}, pmid = {29621980}, issn = {1471-2180}, support = {F32 HD082969/HD/NICHD NIH HHS/United States ; R01 MH107508/MH/NIMH NIH HHS/United States ; K12 GM084897/GM/NIGMS NIH HHS/United States ; R24DK090964//National Institute of Child Health and Human Development/International ; 1RO1DK089201//National Institute of Child Health and Human Development/International ; DP2 OD001500/OD/NIH HHS/United States ; F32HD082969//National Institute of Child Health and Human Development/International ; DP21DP2OD001500//NIH Director New Innovator Pioneer Award/International ; R01 DK089201/DK/NIDDK NIH HHS/United States ; K12GM084897/NH/NIH HHS/United States ; R24 DK090964/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: We and others have previously shown that alterations in the mammalian gut microbiome are associated with diet, notably early life exposure to a maternal high fat diet (HFD). Here, we aimed to further these studies by examining alterations in the gut microbiome of juvenile Japanese macaques (Macaca fuscata) that were exposed to a maternal HFD, weaned onto a control diet, and later supplemented with a synbiotic comprised of psyllium seed and Enterococcus and Lactobacillus species.

RESULTS: Eighteen month old offspring (n = 7) of 36% HFD fed dams were fed a control (14% fat) diet post weaning, then were synbiotic supplemented for 75 days and longitudinal stool and serum samples were obtained. All stool samples were subjected to 16S rRNA metagenomic sequencing, and microbiome profiles and serum lipids and triglycerides were compared to untreated, healthy age matched and diet matched controls (n = 7). Overall, 16S-based metagenomic analysis revealed that supplementation exerted minimal alterations to the gut microbiome including transient increased abundance of Lactobacillus species and decreased abundance of few bacterial genera, including Faecalibacterium and Anaerovibrio. However, serum lipid analysis revealed significant decreases in triglycerides, cholesterol, and LDL (p < 0.05). Nevertheless, supplemented juveniles challenged 4 months later were not protected from HFD-induced gut dysbiosis.

CONCLUSIONS: Synbiotic supplementation is temporally associated with alterations in the gut microbiome and host lipid profiles of juvenile Japanese macaques that were previously exposed to a maternal HFD. Despite these presumptive temporal benefits, a protective effect against later HFD-challenge gut dysbiosis was not observed.}, } @article {pmid29621976, year = {2018}, author = {Noguchi, Y and Ueno, A and Otsubo, M and Katsuno, H and Sugita, I and Kanematsu, Y and Yoshida, A and Esaki, H and Tachi, T and Teramachi, H}, title = {A simple method for exploring adverse drug events in patients with different primary diseases using spontaneous reporting system.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {124}, pmid = {29621976}, issn = {1471-2105}, support = {16K19175//Japan Society for the Promotion of Science/International ; }, mesh = {*Adverse Drug Reaction Reporting Systems ; Area Under Curve ; Chemical and Drug Induced Liver Injury/*diagnosis/etiology ; Databases, Factual ; Humans ; Japan ; Kidney Diseases/chemically induced/*diagnosis ; Pharmacovigilance ; ROC Curve ; }, abstract = {BACKGROUND: Patient background (e.g. age, sex, and primary disease) is an important factor to consider when monitoring adverse drug events (ADEs) for the purpose of pharmacovigilance. However, in disproportionality methods, when additional factors are considered, the number of combinations that have to be computed increases, and it becomes very difficult to explore the whole spontaneous reporting system (SRS). Since the signals need to be detected quickly in pharmacovigilance, a simple exploration method is required. Although association rule mining (AR) is commonly used for the analysis of large data, its application to pharmacovigilance is rare and there are almost no studies comparing AR with conventional signal detection methods.

METHODS: In this study, in order to establish a simple method to explore ADEs in patients with kidney or liver injury as a background disease, the AR and proportional reporting ratio (PRR) signal detection methods were compared. We used oral medicine SRS data from the Japanese Adverse Drug Event Report database (JADER), and used AR as the proposed search method and PRR as the conventional method for comparison. "Rule count ≥ 3", "min lift value > 1", and "min conviction value > 1" were used as the AR detection criteria, and the PRR detection criteria were "Rule count ≥3", "PRR ≥ 2", and "χ2 ≥ 4".

RESULTS: In patients with kidney injury, the AR method had a sensitivity of 99.58%, specificity of 94.99%, and Youden's index of 0.946, while in patients with liver injury, the sensitivity, specificity, and Youden's index were 99.57%, 94.87%, and 0.944, respectively. Additionally, the lift value and the strength of the signal were positively correlated.

CONCLUSIONS: It was suggested that computation using AR might be simple with the detection power equivalent to that of the conventional signal detection method as PRR. In addition, AR can theoretically be applicable to SRS other than JADER. Therefore, complicated conditions (patient's background etc.) that must take factors other than the ADE into consideration can be easily explored by selecting the AR as the first screening for ADE exploration in pharmacovigilance using SRS.}, } @article {pmid29621975, year = {2018}, author = {Tahiri, N and Willems, M and Makarenkov, V}, title = {A new fast method for inferring multiple consensus trees using k-medoids.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {48}, pmid = {29621975}, issn = {1471-2148}, mesh = {*Algorithms ; Archaea/metabolism ; Cluster Analysis ; Computer Simulation ; Gene Transfer, Horizontal/genetics ; Genomics/*methods ; *Phylogeny ; Ribosomal Proteins/metabolism ; Species Specificity ; }, abstract = {BACKGROUND: Gene trees carry important information about specific evolutionary patterns which characterize the evolution of the corresponding gene families. However, a reliable species consensus tree cannot be inferred from a multiple sequence alignment of a single gene family or from the concatenation of alignments corresponding to gene families having different evolutionary histories. These evolutionary histories can be quite different due to horizontal transfer events or to ancient gene duplications which cause the emergence of paralogs within a genome. Many methods have been proposed to infer a single consensus tree from a collection of gene trees. Still, the application of these tree merging methods can lead to the loss of specific evolutionary patterns which characterize some gene families or some groups of gene families. Thus, the problem of inferring multiple consensus trees from a given set of gene trees becomes relevant.

RESULTS: We describe a new fast method for inferring multiple consensus trees from a given set of phylogenetic trees (i.e. additive trees or X-trees) defined on the same set of species (i.e. objects or taxa). The traditional consensus approach yields a single consensus tree. We use the popular k-medoids partitioning algorithm to divide a given set of trees into several clusters of trees. We propose novel versions of the well-known Silhouette and Caliński-Harabasz cluster validity indices that are adapted for tree clustering with k-medoids. The efficiency of the new method was assessed using both synthetic and real data, such as a well-known phylogenetic dataset consisting of 47 gene trees inferred for 14 archaeal organisms.

CONCLUSIONS: The method described here allows inference of multiple consensus trees from a given set of gene trees. It can be used to identify groups of gene trees having similar intragroup and different intergroup evolutionary histories. The main advantage of our method is that it is much faster than the existing tree clustering approaches, while providing similar or better clustering results in most cases. This makes it particularly well suited for the analysis of large genomic and phylogenetic datasets.}, } @article {pmid29621973, year = {2018}, author = {Brenneis, G and Scholtz, G and Beltz, BS}, title = {Comparison of ventral organ development across Pycnogonida (Arthropoda, Chelicerata) provides evidence for a plesiomorphic mode of late neurogenesis in sea spiders and myriapods.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {47}, pmid = {29621973}, issn = {1471-2148}, support = {BR 5039/1-1//Deutsche Forschungsgemeinschaft/International ; BR 5039/2-1//Deutsche Forschungsgemeinschaft/International ; Scho 442/9-1//Deutsche Forschungsgemeinschaft/International ; NSF-IOS-1656103//National Science Foundation/International ; }, mesh = {Animal Structures/*anatomy & histology/cytology/*embryology ; Animals ; Arthropods/*anatomy & histology/classification ; Asymmetric Cell Division ; Bromodeoxyuridine/metabolism ; Cell Movement ; Cell Proliferation ; Deoxyuridine/analogs & derivatives/metabolism ; Larva/anatomy & histology ; *Neurogenesis ; Neurons/cytology ; Phylogeny ; Species Specificity ; }, abstract = {BACKGROUND: Comparative studies of neuroanatomy and neurodevelopment provide valuable information for phylogenetic inference. Beyond that, they reveal transformations of neuroanatomical structures during animal evolution and modifications in the developmental processes that have shaped these structures. In the extremely diverse Arthropoda, such comparative studies contribute with ever-increasing structural resolution and taxon coverage to our understanding of nervous system evolution. However, at the neurodevelopmental level, in-depth data remain still largely confined to comparably few laboratory model organisms. Therefore, we studied postembryonic neurogenesis in six species of the bizarre Pycnogonida (sea spiders), which - as the likely sister group of all remaining chelicerates - promise to illuminate neurodevelopmental changes in the chelicerate lineage.

RESULTS: We performed in vivo cell proliferation experiments with the thymidine analogs 5-bromo-2'-deoxyuridine and 5-ethynl-2'-deoxyuridine coupled to fluorescent histochemical staining and immunolabeling, in order to compare ventral nerve cord anatomy and to localize and characterize centers of postembryonic neurogenesis. We report interspecific differences in the architecture of the subesophageal ganglion (SEG) and show the presence of segmental "ventral organs" (VOs) that act as centers of neural cell production during gangliogenesis. These VOs are either incorporated into the ganglionic soma cortex or found on the external ganglion surface. Despite this difference, several shared features support homology of the two VO types, including (1) a specific arrangement of the cells around a small central cavity, (2) the presence of asymmetrically dividing neural stem cell-like precursors, (3) the migration of newborn cells along corresponding pathways into the cortex, and (4) the same VO origin and formation earlier in development.

CONCLUSIONS: Evaluation of our findings relative to current hypotheses on pycnogonid phylogeny resolves a bipartite SEG and internal VOs as plesiomorphic conditions in pycnogonids. Although chelicerate taxa other than Pycnogonida lack comparable VOs, they are a characteristic feature of myriapod gangliogenesis. Accordingly, we propose internal VOs with neurogenic function to be part of the ground pattern of Arthropoda. Further, our findings illustrate the importance of dense sampling in old arthropod lineages - even if as gross-anatomically uniform as Pycnogonida - in order to reliably differentiate plesiomorphic from apomorphic neurodevelopmental characteristics prior to outgroup comparison.}, } @article {pmid29621972, year = {2018}, author = {Dang, LT and Tondl, M and Chiu, MHH and Revote, J and Paten, B and Tano, V and Tokolyi, A and Besse, F and Quaife-Ryan, G and Cumming, H and Drvodelic, MJ and Eichenlaub, MP and Hallab, JC and Stolper, JS and Rossello, FJ and Bogoyevitch, MA and Jans, DA and Nim, HT and Porrello, ER and Hudson, JE and Ramialison, M}, title = {TrawlerWeb: an online de novo motif discovery tool for next-generation sequencing datasets.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {238}, pmid = {29621972}, issn = {1471-2164}, support = {DP1049980//Australian Research Council/ ; 1049980//National Health and Medical Research Council/ ; }, mesh = {Animals ; Base Sequence ; Binding Sites ; Conserved Sequence ; DNA/chemistry/metabolism ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Internet ; Mice ; Nucleotide Motifs ; Rats ; Sequence Analysis, DNA/*methods ; *Software ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: A strong focus of the post-genomic era is mining of the non-coding regulatory genome in order to unravel the function of regulatory elements that coordinate gene expression (Nat 489:57-74, 2012; Nat 507:462-70, 2014; Nat 507:455-61, 2014; Nat 518:317-30, 2015). Whole-genome approaches based on next-generation sequencing (NGS) have provided insight into the genomic location of regulatory elements throughout different cell types, organs and organisms. These technologies are now widespread and commonly used in laboratories from various fields of research. This highlights the need for fast and user-friendly software tools dedicated to extracting cis-regulatory information contained in these regulatory regions; for instance transcription factor binding site (TFBS) composition. Ideally, such tools should not require prior programming knowledge to ensure they are accessible for all users.

RESULTS: We present TrawlerWeb, a web-based version of the Trawler_standalone tool (Nat Methods 4:563-5, 2007; Nat Protoc 5:323-34, 2010), to allow for the identification of enriched motifs in DNA sequences obtained from next-generation sequencing experiments in order to predict their TFBS composition. TrawlerWeb is designed for online queries with standard options common to web-based motif discovery tools. In addition, TrawlerWeb provides three unique new features: 1) TrawlerWeb allows the input of BED files directly generated from NGS experiments, 2) it automatically generates an input-matched biologically relevant background, and 3) it displays resulting conservation scores for each instance of the motif found in the input sequences, which assists the researcher in prioritising the motifs to validate experimentally. Finally, to date, this web-based version of Trawler_standalone remains the fastest online de novo motif discovery tool compared to other popular web-based software, while generating predictions with high accuracy.

CONCLUSIONS: TrawlerWeb provides users with a fast, simple and easy-to-use web interface for de novo motif discovery. This will assist in rapidly analysing NGS datasets that are now being routinely generated. TrawlerWeb is freely available and accessible at: http://trawler.erc.monash.edu.au .}, } @article {pmid29621971, year = {2018}, author = {Picaud, V and Giovannelli, JF and Truntzer, C and Charrier, JP and Giremus, A and Grangeat, P and Mercier, C}, title = {Linear MALDI-ToF simultaneous spectrum deconvolution and baseline removal.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {123}, pmid = {29621971}, issn = {1471-2105}, support = {ANR 2010 BLAN 0313//BHI-PRO project, ANR/International ; }, mesh = {*Algorithms ; Artifacts ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/*methods ; }, abstract = {BACKGROUND: Thanks to a reasonable cost and simple sample preparation procedure, linear MALDI-ToF spectrometry is a growing technology for clinical microbiology. With appropriate spectrum databases, this technology can be used for early identification of pathogens in body fluids. However, due to the low resolution of linear MALDI-ToF instruments, robust and accurate peak picking remains a challenging task. In this context we propose a new peak extraction algorithm from raw spectrum. With this method the spectrum baseline and spectrum peaks are processed jointly. The approach relies on an additive model constituted by a smooth baseline part plus a sparse peak list convolved with a known peak shape. The model is then fitted under a Gaussian noise model. The proposed method is well suited to process low resolution spectra with important baseline and unresolved peaks.

RESULTS: We developed a new peak deconvolution procedure. The paper describes the method derivation and discusses some of its interpretations. The algorithm is then described in a pseudo-code form where the required optimization procedure is detailed. For synthetic data the method is compared to a more conventional approach. The new method reduces artifacts caused by the usual two-steps procedure, baseline removal then peak extraction. Finally some results on real linear MALDI-ToF spectra are provided.

CONCLUSIONS: We introduced a new method for peak picking, where peak deconvolution and baseline computation are performed jointly. On simulated data we showed that this global approach performs better than a classical one where baseline and peaks are processed sequentially. A dedicated experiment has been conducted on real spectra. In this study a collection of spectra of spiked proteins were acquired and then analyzed. Better performances of the proposed method, in term of accuracy and reproductibility, have been observed and validated by an extended statistical analysis.}, } @article {pmid29620791, year = {2018}, author = {Rossotti, R and Rusconi, C and Baiguera, C and Zilioli, VR and Grillo, G and Merli, M and Ravano, E and Puoti, M}, title = {Feasibility of all-oral anti-HCV treatment during DHAP chemotherapy and autologous stem cell transplantation for T-cell lymphoma.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {242-245}, pmid = {29620791}, issn = {1121-7138}, mesh = {Administration, Oral ; Adult ; Antineoplastic Combined Chemotherapy Protocols/pharmacokinetics/*therapeutic use ; Antiviral Agents/*administration & dosage/*therapeutic use ; Hepatitis C/complications/*drug therapy ; Humans ; Lymphoma, T-Cell/complications/*drug therapy ; Male ; Middle Aged ; }, abstract = {The role of anti-HCV direct-acting agents (DAAs) is well described in HCV-related lymphoproliferative disorders, whereas few data are available on their use in other malignancies, such as aggressive T-cell lymphomas requiring autologous stem cell transplantation (ASCT). We describe two oncologic cirrhotic patients treated with DAAs who underwent ASCT achieving cure for both diseases. Co-administration of sofosbuvir with cisplatin led an unexpected severe kidney impairment that did not resolve 30 weeks after drug exposure. The optimal timing of DAA administration in the ASCT setting has yet to be defined: our experience shows that co-administration is feasible, but requires close monitoring for adverse events.}, } @article {pmid29620790, year = {2018}, author = {Pietropaolo, V and Prezioso, C and Bagnato, F and Antonelli, G}, title = {John Cunningham virus: an overview on biology and disease of the etiological agent of the progressive multifocal leukoencephalopathy.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {179-186}, pmid = {29620790}, issn = {1121-7138}, mesh = {Gene Expression Regulation, Viral ; Genome, Viral ; Humans ; JC Virus/genetics/*physiology ; Leukoencephalopathy, Progressive Multifocal/immunology/pathology/*virology ; }, abstract = {John Cunningham virus (JCV), the etiological agent of progressive multifocal leukoencephalopathy (PML), is the first human polyomavirus described. After asymptomatic primary infection which occurs in childhood, the virus spreads by the hematogenous route from the primary site of infection to secondary sites including kidneys, lymphoid tissues, peripheral blood leukocytes, and brain to establish latent infection. During immunosuppression the virus undergoes molecular rearrangements that allow it to replicate in glial tissues causing PML. PML occurs in people with underlying immunodeficiency or in individuals being treated with potent immunomodulatory therapies. Although the hypothesis that immune deficiency is a predisposing factor for PML, there are many unsolved issues including the pathogenic mechanisms related to the interaction of JCV infection/reactivation with the host. This is due to the difficulty of propagating the virus in human cell cultures and the absence of an animal model. This review updates current understanding in the context of JCV and human disease.}, } @article {pmid29620789, year = {2018}, author = {Piccirilli, G and Chiereghin, A and Gabrielli, L and Giannella, M and Squarzoni, D and Turello, G and Felici, S and Vocale, C and Zuntini, R and Gibertoni, D and Maraolo, AE and Ambretti, S and Lazzarotto, T}, title = {Infectious meningitis/encephalitis: evaluation of a rapid and fully automated multiplex PCR in the microbiological diagnostic workup.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {118-125}, pmid = {29620789}, issn = {1121-7138}, mesh = {Adult ; Automation, Laboratory/*methods ; Bacteria/classification/isolation & purification ; Child ; Encephalitis, Viral/cerebrospinal fluid/*diagnosis ; Female ; Humans ; Male ; Meningitis, Bacterial/cerebrospinal fluid/*diagnosis ; Meningitis, Viral/cerebrospinal fluid/*diagnosis ; Multiplex Polymerase Chain Reaction/*methods ; Viruses/classification/isolation & purification ; }, abstract = {Infectious diseases of the central nervous system (CNS) such as meningitis/encephalitis (ME) require rapid identification of causative pathogens for effective treatment. This study evaluated the analytical performance and clinical utility of a fully automated multiplex PCR test to improve the microbiological diagnostic workup of ME. Seventy-seven cerebrospinal fluid (CSF) samples from 77 patients with suspected ME were studied. The samples were tested by FilmArray™ (FA) ME Panel test and the results were compared with those obtained using conventional microbiological procedures (CMP). Furthermore, the assay's validity was evaluated testing 5 pooled CSF samples positive for different pathogens. The data showed a good concordance (90.9%) between the FA ME panel test and CMP results. Discrepant results were observed in CSF samples with low viral load (5/77) and in samples of patients (2/77) undergoing antimicrobial therapy for fungal infection. The ability of the FA ME panel test to correctly detect the target pathogens was confirmed. Faster microbiological diagnosis was obtained by the FA ME test in comparison to CMP for both bacterial and viral analytes (P<0.001). Implementation of microbiological diagnostic workup with FA ME panel test may improve the management of patients with suspected CNS infection.}, } @article {pmid29620788, year = {2018}, author = {Sorlózano-Puerto, A and Carrillo-Ávila, JA and Gutiérrez-Soto, M and Navarro-Marí, JM and Gutiérrez-Fernández, J}, title = {Susceptibility of clinical isolates of Campylobacter jejuni and Campylobacter coli to colistin.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {235-237}, pmid = {29620788}, issn = {1121-7138}, mesh = {Anti-Bacterial Agents/*pharmacology ; Campylobacter Infections/*microbiology ; Campylobacter coli/*drug effects ; Campylobacter jejuni/*drug effects ; Colistin/*pharmacology ; *Drug Resistance, Bacterial ; Erythromycin/pharmacology ; Humans ; Microbial Sensitivity Tests ; }, abstract = {Campylobacter spp. are one of the most frequent causes of bacterial diarrhea worldwide. Although severe diarrhea is not highly prevalent, the risk of a fatal outcome is increased when infection is caused by strains resistant to macrolides, fluoroquinolones, and/or tetracyclines. It is therefore necessary to test the susceptibility of these bacteria to other antibiotics such as colistin, which may serve as an alternative therapeutic option in these situations. The E-test was used to investigate the activity of erythromycin and colistin against 30 clinical isolates of Campylobacter spp. The MIC values obtained (range: 0.38-8 mg/liter) were sufficiently low, given the elevated concentrations that colistin sulfate can reach in the intestinal lumen, for this antibiotic to be considered useful to treat severe diarrhea caused by Campylobacter spp. resistant to first-line antibiotics.}, } @article {pmid29620787, year = {2018}, author = {Foschi, C and Salvo, M and D'Antuono, A and Gaspari, V and Banzola, N and Cevenini, R and Marangoni, A}, title = {Distribution of genital Mollicutes in the vaginal ecosystem of women with different clinical conditions.}, journal = {The new microbiologica}, volume = {41}, number = {3}, pages = {225-229}, pmid = {29620787}, issn = {1121-7138}, mesh = {Bacterial Load ; Candidiasis, Vulvovaginal/diagnosis/*microbiology ; Female ; Humans ; Tenericutes/*isolation & purification ; Vagina/*microbiology ; Vaginosis, Bacterial/diagnosis/*microbiology ; }, abstract = {Ureaplasma urealyticum (UU), Ureaplasma parvum (UP), Mycoplasma hominis (MH) and Mycoplasma genitalium (MG) are the most common Mollicutes of the female genital tract. Although many studies have addressed their possible role in the vaginal ecosystem, many aspects remain to be elucidated. The aim of this study was to evaluate the vaginal presence of ureaplasmas/mycoplasmas in women with different clinical conditions. By means of quantitative PCR assays, the prevalence and load of each Mollicute were assessed in different groups of pre-menopausal women: 'healthy' (n=29), women with bacterial vaginosis (BV) (n=21), patients with Chlamydia trachomatis (CT) infection (n=25) and subjects with vulvo-vaginal candidiasis (VVC) (n=23). Globally, UP was the most prevalent Mollicutes in the vagina (67.3%), followed by MH (14.3%), UU (9.2%) and MG (3.1%). The presence of UU and UP was almost never associated. MH showed a significantly higher prevalence and higher bacterial loads in BV-positive women (P<0.05), whereas patients with CT and VVC were characterized by a Mollicutes pattern similar to healthy women. Mollicutes can be frequently found in the vaginal ecosystem, even in asymptomatic 'healthy' women. Although its presence is not a strict requirement, MH displays a significant role in the pathogenesis of BV.}, } @article {pmid29620766, year = {2018}, author = {Stocker, M}, title = {How philosophy was squeezed out of the PhD.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {31}, doi = {10.1038/d41586-018-04051-1}, pmid = {29620766}, issn = {1476-4687}, mesh = {Education, Graduate ; *Philosophy ; Thinking ; }, } @article {pmid29620765, year = {2018}, author = {Willyard, C}, title = {Squeaky clean mice could be ruining research.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {16-18}, doi = {10.1038/d41586-018-03916-9}, pmid = {29620765}, issn = {1476-4687}, mesh = {Adult ; Animals ; Animals, Laboratory/genetics/*immunology/microbiology/virology ; Animals, Wild/*immunology/*microbiology/virology ; Biomedical Research/*methods ; *Disease Models, Animal ; Fecal Microbiota Transplantation/veterinary ; Female ; Gene Expression Profiling ; Germ-Free Life/immunology ; *Housing, Animal ; Humans ; Immunologic Memory/immunology ; Infant ; Listeria monocytogenes/immunology ; Listeriosis/immunology/microbiology/veterinary ; Mice ; Microbiota/immunology ; Pregnancy ; T-Lymphocytes/cytology/immunology ; Yellow Fever Vaccine/administration & dosage/immunology ; }, } @article {pmid29620764, year = {2018}, author = {Simon, S}, title = {Günter Blobel (1936-2018).}, journal = {Nature}, volume = {556}, number = {7699}, pages = {32}, doi = {10.1038/d41586-018-03849-3}, pmid = {29620764}, issn = {1476-4687}, support = {R01 GM119585/GM/NIGMS NIH HHS/United States ; R56 CA207929/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Biology/*history ; Germany ; History, 20th Century ; Humans ; New York City ; Nobel Prize ; Organelles/metabolism ; Protein Sorting Signals/*physiology ; Protein Transport ; Proteins/*metabolism ; }, } @article {pmid29620763, year = {2018}, author = {}, title = {Time to talk about why so many postgrads have poor mental health.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {5}, doi = {10.1038/d41586-018-04023-5}, pmid = {29620763}, issn = {1476-4687}, mesh = {Humans ; *Mental Health ; }, } @article {pmid29620761, year = {2018}, author = {Schiermeier, Q}, title = {EU copyright reforms draw fire from scientists.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {14-15}, doi = {10.1038/d41586-018-03837-7}, pmid = {29620761}, issn = {1476-4687}, mesh = {Copyright/economics/*legislation & jurisprudence ; *European Union ; *Information Dissemination ; Open Access Publishing/economics/*legislation & jurisprudence ; Research/economics ; *Research Personnel/economics/psychology ; }, } @article {pmid29620760, year = {2018}, author = {Patel, S}, title = {Two-pore channels open up.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {38-40}, doi = {10.1038/d41586-018-02783-8}, pmid = {29620760}, issn = {1476-4687}, mesh = {Humans ; *Ion Channel Gating ; *Potassium Channels ; }, } @article {pmid29620759, year = {2018}, author = {Shah, H}, title = {Use our personal data for the common good.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {7}, doi = {10.1038/d41586-018-03912-z}, pmid = {29620759}, issn = {1476-4687}, } @article {pmid29620758, year = {2018}, author = {Hansson, GK}, title = {Alfred Nobel's 1895 will is strictly upheld to this day.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {31}, doi = {10.1038/d41586-018-04050-2}, pmid = {29620758}, issn = {1476-4687}, mesh = {History, 20th Century ; Humans ; *Nobel Prize ; }, } @article {pmid29620757, year = {2018}, author = {}, title = {Canada gains popularity with prospective students.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {141}, doi = {10.1038/d41586-018-03928-5}, pmid = {29620757}, issn = {1476-4687}, } @article {pmid29620756, year = {2018}, author = {St George, S}, title = {Mississippi rising.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {34-35}, doi = {10.1038/d41586-018-03243-z}, pmid = {29620756}, issn = {1476-4687}, } @article {pmid29620755, year = {2018}, author = {Kwok, R}, title = {Ecology's remote-sensing revolution.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {137-138}, doi = {10.1038/d41586-018-03924-9}, pmid = {29620755}, issn = {1476-4687}, mesh = {Animals ; Cloud Computing ; Conservation of Natural Resources ; Data Interpretation, Statistical ; *Datasets as Topic ; Ecology/instrumentation/*methods ; Machine Learning ; Satellite Imagery/instrumentation/*methods/*statistics & numerical data ; Software ; United States ; United States National Aeronautics and Space Administration ; }, } @article {pmid29620754, year = {2018}, author = {Soderblom, D}, title = {Uptick in US female members of International Astronomical Union.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {31}, doi = {10.1038/d41586-018-04053-z}, pmid = {29620754}, issn = {1476-4687}, mesh = {*Astronomy ; Female ; Humans ; }, } @article {pmid29620753, year = {2018}, author = {Haddad, L}, title = {Reward food companies for improving nutrition.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {19-22}, doi = {10.1038/d41586-018-03918-7}, pmid = {29620753}, issn = {1476-4687}, mesh = {Advertising as Topic/economics/statistics & numerical data ; Child ; Dietary Sugars/adverse effects/supply & distribution ; Female ; Food Industry/*economics/*methods/trends ; Healthy Diet/*economics/*trends ; Humans ; Infant ; Infant, Newborn ; Lobbying ; Marketing ; *Nutrition Policy/economics/trends ; *Nutritional Status ; Pregnancy ; Public-Private Sector Partnerships/economics/trends ; Punishment ; *Reward ; }, } @article {pmid29620751, year = {2018}, author = {Mele, EJ}, title = {Novel electronic states seen in graphene.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {37-38}, doi = {10.1038/d41586-018-02660-4}, pmid = {29620751}, issn = {1476-4687}, mesh = {*Graphite ; Particle Size ; *Surface Properties ; }, } @article {pmid29620750, year = {2018}, author = {Alberstein, RG and Tezcan, FA}, title = {Observations of the birth of crystals.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {41-42}, doi = {10.1038/d41586-018-03801-5}, pmid = {29620750}, issn = {1476-4687}, } @article {pmid29620748, year = {2018}, author = {}, title = {Rogue space station, CRISPR crops and French AI pledge.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {10}, doi = {10.1038/d41586-018-03913-y}, pmid = {29620748}, issn = {1476-4687}, } @article {pmid29620747, year = {2018}, author = {Ledford, H}, title = {Cancer researchers push to relax rules for clinical trials.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {12-13}, doi = {10.1038/d41586-018-03355-6}, pmid = {29620747}, issn = {1476-4687}, mesh = {Humans ; *Neoplasms ; *Research Personnel ; }, } @article {pmid29620745, year = {2018}, author = {Rahman, AA and Artaxo, P and Asrat, A and Parker, A}, title = {Developing countries must lead on solar geoengineering research.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {22-24}, doi = {10.1038/d41586-018-03917-8}, pmid = {29620745}, issn = {1476-4687}, } @article {pmid29620744, year = {2018}, author = {Hurdle, JG and Deshpande, A}, title = {Bacterial persister cells tackled.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {40-41}, doi = {10.1038/d41586-018-03440-w}, pmid = {29620744}, issn = {1476-4687}, mesh = {Anti-Bacterial Agents ; Drug Resistance, Bacterial/*drug effects ; *Microbial Sensitivity Tests ; }, } @article {pmid29620743, year = {2018}, author = {Baquero, F and Gutiérrez-Fuentes, JA}, title = {Sciences unite in Spain to promote research for advancing society.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {31}, doi = {10.1038/d41586-018-04052-0}, pmid = {29620743}, issn = {1476-4687}, mesh = {Humans ; Public Policy ; Research/economics/*organization & administration/*trends ; *Social Change ; Spain ; }, } @article {pmid29620741, year = {2018}, author = {Luyssaert, S and Cornelissen, JHC}, title = {Forests in flux as climate varies.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {35-37}, doi = {10.1038/d41586-018-02858-6}, pmid = {29620741}, issn = {1476-4687}, mesh = {*Climate ; Climate Change ; *Forests ; Trees ; }, } @article {pmid29620740, year = {2018}, author = {Witze, A}, title = {NASA reveals major delay for $8-billion Hubble successor.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {11-12}, doi = {10.1038/d41586-018-03863-5}, pmid = {29620740}, issn = {1476-4687}, } @article {pmid29620739, year = {2018}, author = {Leeming, J}, title = {How researchers are ensuring that their work has an impact.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {139-141}, doi = {10.1038/d41586-018-03925-8}, pmid = {29620739}, issn = {1476-4687}, mesh = {Industry ; *Motivation ; Research Personnel/*psychology/*standards ; *Social Change ; *Translational Medical Research ; Workforce ; }, } @article {pmid29620738, year = {2018}, author = {Castelvecchi, D}, title = {Beguiling dark-matter signal persists 20 years on.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {13-14}, doi = {10.1038/d41586-018-03991-y}, pmid = {29620738}, issn = {1476-4687}, } @article {pmid29620737, year = {2018}, author = {}, title = {Nature: the truth.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {5}, doi = {10.1038/d41586-018-04024-4}, pmid = {29620737}, issn = {1476-4687}, mesh = {Authorship ; *Editorial Policies ; *Peer Review, Research/methods/standards ; *Periodicals as Topic ; Social Change ; Truth Disclosure ; }, } @article {pmid29620736, year = {2018}, author = {Heuer, R and Nurse, P}, title = {Uphold Hawking's and Sulston's support for European science.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {31}, doi = {10.1038/d41586-018-04049-9}, pmid = {29620736}, issn = {1476-4687}, mesh = {Europe ; European Union ; Humans ; *Science ; }, } @article {pmid29620735, year = {2018}, author = {}, title = {Female leadership falls at top universities.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {141}, doi = {10.1038/d41586-018-03927-6}, pmid = {29620735}, issn = {1476-4687}, } @article {pmid29620734, year = {2018}, author = {Munoz, SE and Giosan, L and Therrell, MD and Remo, JWF and Shen, Z and Sullivan, RM and Wiman, C and O'Donnell, M and Donnelly, JP}, title = {Climatic control of Mississippi River flood hazard amplified by river engineering.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {95-98}, pmid = {29620734}, issn = {1476-4687}, mesh = {Disasters/*statistics & numerical data ; El Nino-Southern Oscillation ; Floods/*statistics & numerical data ; Geologic Sediments/analysis ; Human Activities ; Hydrology/*statistics & numerical data ; Mississippi ; *Risk Assessment ; *Rivers ; Trees/growth & development ; *Water Movements ; }, abstract = {Over the past century, many of the world's major rivers have been modified for the purposes of flood mitigation, power generation and commercial navigation. Engineering modifications to the Mississippi River system have altered the river's sediment levels and channel morphology, but the influence of these modifications on flood hazard is debated. Detecting and attributing changes in river discharge is challenging because instrumental streamflow records are often too short to evaluate the range of natural hydrological variability before the establishment of flood mitigation infrastructure. Here we show that multi-decadal trends of flood hazard on the lower Mississippi River are strongly modulated by dynamical modes of climate variability, particularly the El Niño-Southern Oscillation and the Atlantic Multidecadal Oscillation, but that the artificial channelization (confinement to a straightened channel) has greatly amplified flood magnitudes over the past century. Our results, based on a multi-proxy reconstruction of flood frequency and magnitude spanning the past 500 years, reveal that the magnitude of the 100-year flood (a flood with a 1 per cent chance of being exceeded in any year) has increased by 20 per cent over those five centuries, with about 75 per cent of this increase attributed to river engineering. We conclude that the interaction of human alterations to the Mississippi River system with dynamical modes of climate variability has elevated the current flood hazard to levels that are unprecedented within the past five centuries.}, } @article {pmid29620733, year = {2018}, author = {Hailey, CJ and Mori, K and Bauer, FE and Berkowitz, ME and Hong, J and Hord, BJ}, title = {A density cusp of quiescent X-ray binaries in the central parsec of the Galaxy.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {70-73}, pmid = {29620733}, issn = {1476-4687}, abstract = {The existence of a 'density cusp'-a localized increase in number-of stellar-mass black holes near a supermassive black hole is a fundamental prediction of galactic stellar dynamics. The best place to detect such a cusp is in the Galactic Centre, where the nearest supermassive black hole, Sagittarius A*, resides. As many as 20,000 black holes are predicted to settle into the central parsec of the Galaxy as a result of dynamical friction; however, so far no density cusp of black holes has been detected. Low-mass X-ray binary systems that contain a stellar-mass black hole are natural tracers of isolated black holes. Here we report observations of a dozen quiescent X-ray binaries in a density cusp within one parsec of Sagittarius A*. The lower-energy emission spectra that we observed in these binaries is distinct from the higher-energy spectra associated with the population of accreting white dwarfs that dominates the central eight parsecs of the Galaxy. The properties of these X-ray binaries, in particular their spatial distribution and luminosity function, suggest the existence of hundreds of binary systems in the central parsec of the Galaxy and many more isolated black holes. We cannot rule out a contribution to the observed emission from a population (of up to about one-half the number of X-ray binaries) of rotationally powered, millisecond pulsars. The spatial distribution of the binary systems is a relic of their formation history, either in the stellar disk around Sagittarius A* (ref. 7) or through in-fall from globular clusters, and constrains the number density of sources in the modelling of gravitational waves from massive stellar remnants, such as neutron stars and black holes.}, } @article {pmid29620732, year = {2018}, author = {Knott, SRV and Wagenblast, E and Khan, S and Kim, SY and Soto, M and Wagner, M and Turgeon, MO and Fish, L and Erard, N and Gable, AL and Maceli, AR and Dickopf, S and Papachristou, EK and D'Santos, CS and Carey, LA and Wilkinson, JE and Harrell, JC and Perou, CM and Goodarzi, H and Poulogiannis, G and Hannon, GJ}, title = {Erratum: Asparagine bioavailability governs metastasis in a model of breast cancer.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {135}, pmid = {29620732}, issn = {1476-4687}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; }, abstract = {This corrects the article DOI: 10.1038/nature25465.}, } @article {pmid29620731, year = {2018}, author = {Liu, Y and Granet, D and Lin, H and Baxter, S and Ouyang, H and Zhu, J and Huang, S and Liu, Z and Wu, X and Yan, F and Liu, X and Luo, L and Heichel, C and Zhang, M and Cai, W and Maas, RL and Zhang, K}, title = {Liu et al. reply.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {E3-E4}, pmid = {29620731}, issn = {1476-4687}, } @article {pmid29620730, year = {2018}, author = {Van Driessche, AES and Van Gerven, N and Bomans, PHH and Joosten, RRM and Friedrich, H and Gil-Carton, D and Sommerdijk, NAJM and Sleutel, M}, title = {Molecular nucleation mechanisms and control strategies for crystal polymorph selection.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {89-94}, pmid = {29620730}, issn = {1476-4687}, mesh = {Aldose-Ketose Isomerases/*chemistry/genetics/ultrastructure ; Ammonium Sulfate/chemistry/pharmacology ; Binding Sites ; Cryoelectron Microscopy ; Crystallization/*methods ; Gels/chemistry/pharmacology ; Microscopy, Electron, Transmission ; Mutagenesis, Site-Directed ; Nanoparticles/*chemistry/ultrastructure ; Phase Transition/drug effects ; Polyethylene Glycols/chemistry/pharmacology ; Streptomyces/enzymology ; }, abstract = {The formation of condensed (compacted) protein phases is associated with a wide range of human disorders, such as eye cataracts, amyotrophic lateral sclerosis, sickle cell anaemia and Alzheimer's disease. However, condensed protein phases have their uses: as crystals, they are harnessed by structural biologists to elucidate protein structures, or are used as delivery vehicles for pharmaceutical applications. The physiochemical properties of crystals can vary substantially between different forms or structures ('polymorphs') of the same macromolecule, and dictate their usability in a scientific or industrial context. To gain control over an emerging polymorph, one needs a molecular-level understanding of the pathways that lead to the various macroscopic states and of the mechanisms that govern pathway selection. However, it is still not clear how the embryonic seeds of a macromolecular phase are formed, or how these nuclei affect polymorph selection. Here we use time-resolved cryo-transmission electron microscopy to image the nucleation of crystals of the protein glucose isomerase, and to uncover at molecular resolution the nucleation pathways that lead to two crystalline states and one gelled state. We show that polymorph selection takes place at the earliest stages of structure formation and is based on specific building blocks for each space group. Moreover, we demonstrate control over the system by selectively forming desired polymorphs through site-directed mutagenesis, specifically tuning intermolecular bonding or gel seeding. Our results differ from the present picture of protein nucleation, in that we do not identify a metastable dense liquid as the precursor to the crystalline state. Rather, we observe nucleation events that are driven by oriented attachments between subcritical clusters that already exhibit a degree of crystallinity. These insights suggest ways of controlling macromolecular phase transitions, aiding the development of protein-based drug-delivery systems and macromolecular crystallography.}, } @article {pmid29620729, year = {2018}, author = {Vavvas, DG and Dryja, TP and Wilson, ME and Olsen, TW and Shah, A and Jurkunas, U and Pineda, R and Poulaki, V and Palioura, S and Veldman, P and Moreno-Montañés, J and Pinazo-Duran, MD and Pastor, JC and Tsilimbaris, M and Rhee, D and Colby, K and Hunter, DG and Thanos, S and Sakamoto, T and Pasquale, LR and Miller, JW and VanderVeen, D and Lambert, SR}, title = {Lens regeneration in children.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {E2-E3}, pmid = {29620729}, issn = {1476-4687}, } @article {pmid29620728, year = {2018}, author = {Solebo, AL and Hammond, CJ and Rahi, JS}, title = {Improving outcomes in congenital cataract.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {E1-E2}, pmid = {29620728}, issn = {1476-4687}, } @article {pmid29620727, year = {2018}, author = {Cohen, LJ and Esterhazy, D and Kim, SH and Lemetre, C and Aguilar, RR and Gordon, EA and Pickard, AJ and Cross, JR and Emiliano, AB and Han, SM and Chu, J and Vila-Farres, X and Kaplitt, J and Rogoz, A and Calle, PY and Hunter, C and Bitok, JK and Brady, SF}, title = {Corrigendum: Commensal bacteria make GPCR ligands that mimic human signalling molecules.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {135}, pmid = {29620727}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23874.}, } @article {pmid29620726, year = {2018}, author = {He, Y and Han, Y and Stamenov, P and Kundys, B and Coey, JMD and Jiang, C and Xu, H}, title = {Investigating non-Joulian magnetostriction.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {E5-E7}, pmid = {29620726}, issn = {1476-4687}, } @article {pmid29620725, year = {2018}, author = {Ma, Z and Guo, D and Xu, X and Lu, M and Bardgett, RD and Eissenstat, DM and McCormack, ML and Hedin, LO}, title = {Erratum: Evolutionary history resolves global organization of root functional traits.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {135}, pmid = {29620725}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature25783.}, } @article {pmid29620504, year = {2018}, author = {Choi, KD and Siddiqi, MZ and Liu, Q and Jo, JH and Chun, SY and Choi, GM and Kim, SY and Lee, SY and Im, WT}, title = {Polaromonas ginsengisoli sp. nov., isolated from ginseng field soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1436-1441}, doi = {10.1099/ijsem.0.002669}, pmid = {29620504}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Comamonadaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Panax/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-reaction-negative, strictly aerobic, milky-white and rod-shaped bacterium (designated Gsoil 115T) isolated from ginseng field soil was characterized by a polyphasic approach to clarify its taxonomic position. Strain Gsoil 115T grew optimally at 30 °C and at pH 7.0 on Reasoner's 2A agar medium. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain Gsoil 115T belongs to the genus Polaromonas and was most closely related to Polaromonaseurypsychrophila B717-2T (98.6 %), Polaromonasvacuolata 34-PT (98.3 %), Polaromonasjejuensis NBRC 106434T (98.1 %), Polaromonas aquatic CCUG 39402T (97.7 %) and Polaromonascryoconiti Cr4-35T (97.5 %). The DNA G+C content was 60.9 mol%. The DNA-DNA hybridization relatedness between strain Gsoil 115T and P. eurypsychrophila B717-2T, P. vacuolata 34-PT, P. jejuensis NBRC 106434T, P. aquatic CCUG 39402T and P. cryoconiti Cr4-35T were 31.2, 21.6, 16.9, 8.7 and 10.1 %, respectively. The major polar lipids were phosphatidylglycerol (PG), diphosphatidylglycerol (DPG) and phosphatidylethanolamine (PE). The sole respiratory quinone was Q-8. The major fatty acids were C16 : 0 and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), which supported the affiliation of strain Gsoil 115T to the genus Polaromonas. Moreover, the physiological, biochemical and low level of DNA-DNA relatedness value allowed the phenotypic and genotypic differentiation of strain Gsoil 115T from the recognized species of the genus Polaromonas. Therefore, strain Gsoil 115T represents a novel species of the genus Polaromonas, for which the name Polaromonas ginsengisoli sp. nov. is proposed, with the type strain Gsoil 115T (LMG 23393T=KCTC 12577T).}, } @article {pmid29620503, year = {2018}, author = {Tang, L and Zhang, Z and Zhou, C and Cui, R and Tian, Y and Zhang, Y}, title = {Roseicyclus marinus sp. nov., isolated from a Synechococcus culture, and emended description of the genus Roseicyclus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1781-1786}, doi = {10.1099/ijsem.0.002752}, pmid = {29620503}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteriochlorophyll A/chemistry ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phosphatidylcholines/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/microbiology ; Sequence Analysis, DNA ; *Synechococcus ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative, aerobic, non-flagellated, pink-pigmented and rod-shaped strain with gliding motility, designated strain CCMM001T, was isolated from a mixed culture of Synechococcus species PCC7002 and a natural bacterial community from a sample of offshore seawater from Qingdao, China, during September 2014. The strain contained bacteriochlorophyll a with a small peak at 802 nm and a large in vivo absorption band at 870 nm. Strain CCMM001T grew optimally at pH 7.0 and 30 °C in the presence of 3 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain CCMM001T is most closely related to the genus Roseicyclus and its type and only species Roseicyclus mahoneyensis ML6T with 96.9 % sequence similarity. The polar lipids of strain CCMM001T consisted of phosphatidylethanolamine, phosphatidylcholine, one unidentified aminolipid, and five unidentified lipids. The predominant isoprenoid quinone was Q-10. The major fatty acids included C18 : 1ω7c and C19 : 0cyclo ω8c. The DNA G+C content of strain CCMM001T was 63.5 mol%. These phylogenetic, physiological and chemotaxonomic data indicated that strain CCMM001T represents a novel species of the genus Roseicyclus, for which the name Roseicyclus marinus sp. nov. is proposed. The type strain is CCMM001T (=MCCC 1K03242T=KCTC 52641T).}, } @article {pmid29620502, year = {2018}, author = {Trachsel, J and Humphrey, S and Allen, HK}, title = {Butyricicoccus porcorum sp. nov., a butyrate-producing bacterium from swine intestinal tract.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1737-1742}, doi = {10.1099/ijsem.0.002738}, pmid = {29620502}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Butyrates/*metabolism ; Clostridiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Ileum/*microbiology ; Iowa ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Swine/*microbiology ; }, abstract = {A Gram-stain-positive, non-motile, butyrate-producing coccus was cultured from the distal ileum of swine. This organism was isolated on rumen-fluid medium, consumes acetate, and produces butyrate as its major end product when grown on mono- and di-saccharides. A phylogenetic analysis based on near full-length 16S rRNA gene sequences as well as whole-genome phylogenies suggests that this isolate is most closely related to species in the genus Butyricicoccus, with Butyricicoccus pullicaecorum being the closest named relative (93.5 % 16S similarity). The G+C content of this isolate is 54 mol%, and the major cellular fatty acids are C18 : 0 DMA, C14 : 0, C18 : 1ω9c and C16 : 0. These data indicate that this isolate represents a novel species within the genus Butyricicoccus, for which the name Butyricicoccus porcorum sp. nov. is proposed. The type strain of Butyricicoccus porcorum is BB10T (ATCC TSD-102T, DSM 104997T).}, } @article {pmid29620500, year = {2018}, author = {Ju, Z and Zhang, R and Hou, XJ and Han, SB and Li, Y and Sun, C and Wu, M and Xu, L}, title = {Kordiimonas pumila sp. nov., isolated from coastal sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1743-1748}, doi = {10.1099/ijsem.0.002740}, pmid = {29620500}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative, translucent-white, aerobic, motile and rod-shaped strain, designated N18T, was isolated from a coastal sediment sample collected in Zhoushan, Zhejiang Province, China. 16S rRNA gene similarity analysis revealed that strain N18T demonstrated highest similarity to the genus Kordiimonas(95.3-97.2 %). Phylogenetic analysis of 16S rRNA gene sequence showed that strain N18T represented a distinct lineage in the clade consisting of the genus Kordiimonas. Strain N18T was found to grow at 10-37 °C (optimum 28 °C), pH 6.0-8.0 (optimum 7.0) and with 1.0-4.0 % (w/v) NaCl (optimum 2.5 %). The G+C content of the genomic DNA was 55.3 mol%. The major cellular fatty acids were identified as summed feature 3 (comprising iso-C15 : 0 2-OH/C16 : 1ω7c), iso-C17 : 1ω9c and iso-C15 : 0. The polar lipid profile of N18T consisted of phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, an unidentified glycolipid, an unidentified aminoglycolipid, an unidentified aminophospholipid and five unidentified lipids. The respiratory quinone was Q-10. Based on chemotaxonomic, morphological and physiological properties, strain N18T could be distinguished from its closest phylogenetic neighbours. Thus, we propose Kordiimonas pumila sp. nov., the type strain is N18T (=MCCC 1K03436T=KCTC 62164T).}, } @article {pmid29620498, year = {2018}, author = {Sun, J and Wang, W and Ying, Y and Zhu, X and Liu, J and Hao, J}, title = {Pseudomonas profundi sp. nov., isolated from deep-sea water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1776-1780}, doi = {10.1099/ijsem.0.002748}, pmid = {29620498}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Pacific Ocean ; Phospholipids/chemistry ; *Phylogeny ; Pseudomonas/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic bacterium, strain M5T, was isolated from a seawater sample collected from the western Pacific Ocean at a depth of 1000 m and characterized by using polyphasic taxonomy. Cells of the strain were rod-shaped and motile by a single polar flagellum. Cells grew at 4-40 °C (optimum, 25 °C), at pH 7-10 (optimum, 9) and with 0-10 % NaCl (optimum, 1-2 %). Phylogenetic trees based on 16S rRNA gene sequences showed that strain M5T was associated with the genus Pseudomonas, and showed highest similarities to Pseudomonas pelagia CL-AP6T (97.8 %) and Pseudomonas salina XCD-X85T (97.5 %) and Pseudomonas sabulinigri J64T (96.4 %). The average nucleotide identity scores for strains CL-AP6T and XCD-X85T were 74.6 % and 73.7 %, the Genome-to-Genome Distance Calculator scores were 15.8-19.5 % and 15.4-19.7 %, and the species identification scores were 92.3 % and 92.4 %. The major isoprenoid quinone of strain M5T was ubiquinone (Q-9) and the major cellular fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c; 33.2 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c; 22.8 %) and C16 : 0 (13 %). The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and some unidentified lipids. The phylogenetic analysis and physiological and biochemical data showed that strain M5T should be classified as representing a novel species in the genus Pseudomonas, for which the name Pseudomonas profundi sp. nov. is proposed. The type strain is M5T (=CCTCC AB 2017186T=KCTC 62119T=CICC 24308T).}, } @article {pmid29620497, year = {2018}, author = {Park, AY and Teeravet, S and Pheng, S and Lee, JR and Kim, SG and Suwannachart, C}, title = {Sulfitobacter aestuarii sp. nov., a marine bacterium isolated from a tidal flat of the Yellow Sea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1771-1775}, doi = {10.1099/ijsem.0.002747}, pmid = {29620497}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel bacterial strain, designated hydD52T, was isolated from a sample of tidal flat sediment of the Yellow Sea in the Republic of Korea. The cells were motile, rod-shaped and Gram-stain-negative. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that strain hydD52T was a member of the genus Sulfitobacter and most closely related to Sulfitobacter dubius DSM 16472T (98.0 %), Sulfitobacter indolifex HEL-45T (97.8 %) and Sulfitobacter delicatus DSM 28223T (97.6 %). The major fatty acids (>5 %) of hydD52T were C18 : 1ω7c/C18 : 1ω6c, C16 : 0, C18 : 1ω7c 11-methyl and C19 : 0ω8c. The respiratory quinone of strain hydD52T was ubiquinone-10. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and an unidentified amino lipid. The G+C content of this strain was 64.0 mol%. The DNA-DNA relatedness values of hydD52T with the type strains of S. dubius, S. indolifex and S. delicatus were 18.8, 13.1 and 15.7 %, respectively. Based on the results of morphological, physiological and chemotaxonomic characterization, DNA-DNA hybridization relatedness, and 16S rRNA genes analysis, we concluded that strain hydD52T represents a novel species, for which the name Sulfitobacter aestuarii sp. nov. is proposed. The type strain is hydD52T (=KCTC 32982T=TISTR 2562T).}, } @article {pmid29620496, year = {2018}, author = {Song, W and Duan, L and Jin, L and Zhao, J and Jiang, S and Sun, T and Guo, XW and Xiang, W and Wang, X}, title = {Streptacidiphilus monticola sp. nov., a novel actinomycete isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1757-1761}, doi = {10.1099/ijsem.0.002751}, pmid = {29620496}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinobacterium, designated strain NEAU-SW11T, was isolated from soil collected from Binxian, Heilongjiang province, north China. The isolate was found to have chemical and morphological properties of the genus Streptacidiphilus, with the highest sequence similarities to Streptacidiphilus anmyonensis JCM 16223T (98.1 %), Streptacidiphilus jiangxiensis JCM 12277T (97.8 %), Streptacidiphilus melanogenes JCM 16224T (97.6 %) and Streptacidiphilus rugosus JCM 16225T (97.4 %) and it phylogenetically clustered with these four strains. The cell wall contained ll-diaminopimelic acid as the major diamino acid and the whole-cell hydrolysates were rhamnose, ribose, glucose and galactose. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside and two unidentified phospholipids. The predominant menaquinones were MK-9(H8) and MK-9(H6). The major fatty acids were C16 : 0, anteiso-C17 : 0, C14 : 0 and C15 : 0. The DNA G+C content was 71.0 mol%. However, DNA-DNA hybridization, physiological and biochemical data showed that strain NEAU-SW11T could be distinguished from its closest relatives. Therefore, strain NEAU-SW11T represents a novel species of the genus Streptacidiphilus, for which the name Streptacidiphilus monticola sp. nov. is proposed. The type strain is NEAU-SW11T (=CGMCC 4.7427T=DSM 105744T).}, } @article {pmid29620495, year = {2018}, author = {Liu, Q and Siddiqi, MZ and Liu, Q and Huq, MA and Lee, SY and Choi, KD and Im, WT}, title = {Flavobacterium hankyongi sp. nov., isolated from activated sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1732-1736}, doi = {10.1099/ijsem.0.002739}, pmid = {29620495}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Sewage/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated strain KTCe-4T, was isolated from activated sludge. Based on 16S rRNA gene sequencing and phylogenetic analysis, the novel isolate was found to belong to the genus Flavobacterium and was most closely related to Flavobacteriumterrae DSM 18829T (97.8 %), Flavobacteriumvireti THG-SM1T (97.8 %), Flavobacteriumbrevivitae TTM-43T (97.4 %) and shared <96.4 % sequence similarity to the other members of the genus. Strain KTCe-4T contained MK-6 as the predominant isoprenoid quinone and iso-C15 : 0, iso-C15 : 0 G, iso-C15 : 0 3-OH, iso-C17 : 0 3-OH and iso-C17 : 1ω9c, as the major fatty acids. The major polar lipids were phosphatidylethanolamine, two unidentified polar lipids and one unknown amino lipid. The DNA-DNA relatedness values of strain KTCe-4T with respect to type strains of recognized species of the genus Flavobacterium were less than 70 %. Based on 16S rRNA gene sequencing, low values of DNA-DNA hybridization and polyphasic taxonomic analysis, strain KTCe-4T represents a novel species within the genus Flavobacterium, for which the name Flavobacterium hankyongi sp. nov. is proposed. The type strain of Flavobacterium hankyongi is strain KTCe-4T (=KACC 16613T=JCM 18198T).}, } @article {pmid29620494, year = {2018}, author = {Chaudhary, DK and Kim, J}, title = {Rhodococcus olei sp. nov., with the ability to degrade petroleum oil, isolated from oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1749-1756}, doi = {10.1099/ijsem.0.002750}, pmid = {29620494}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nepal ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; *Petroleum Pollution ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodococcus/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, non-motile, creamy-white and rod-coccus shaped actinobacterium, designated strain Ktm-20T, capable of degrading petroleum oil was isolated from oil-contaminated soil. Strain Ktm-20T was able to grow at 15-37 °C, at pH 5.5-10.0 and at 0.0-2.0 % (w/v) NaCl concentration. This strain was taxonomically characterized by a polyphasic approach. The 16S rRNA gene sequence analysis showed that strain Ktm-20T belonged to the genus Rhodococcus and is closely related to Rhodococcus triatomae DSM 44892T, Rhodococcus pedocola UC12T, Rhodococcus wratislaviensis NBRC 100605T, Rhodococcus agglutinans CFH S0262T and Rhodococcus canchipurensis MBRL 353T (98.8, 98.7, 98.5, 98.4 and 98.3 % gene sequence similarity, respectively). The only respiratory quinone was MK-8(H2); the major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylinositol and phosphatidylinositol mannoside; and the predominant fatty acids were C16 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C18 : 1ω9c. The cell-wall peptidoglycan contained meso-diaminopimelic acid; and galactose, glucose, arabinose and ribose were detected as diagnostic sugars from whole-cell hydrolysates. Mycolic acids were detected. The DNA G+C content was 70.9 mol%. The DNA-DNA relatedness values between strain Ktm-20T and closely related species of the genus Rhodococcus were between 38.3-25.3 %, which falls below the threshold value of 70 % for the strain to be considered as novel. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain Ktm-20T represents a novel species of the genus Rhodococcus, for which the name Rhodococcus olei sp. nov. is proposed. The type strain is Ktm-20T (=KEMB 9005-695T=KACC 19390T=JCM 32206T).}, } @article {pmid29620493, year = {2018}, author = {Franco, A and Busse, HJ and Schubert, P and Wilke, T and Kämpfer, P and Glaeser, SP}, title = {Winogradskyella pocilloporae sp. nov. isolated from healthy tissue of the coral Pocillopora damicornis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1689-1696}, doi = {10.1099/ijsem.0.002731}, pmid = {29620493}, issn = {1466-5034}, mesh = {Animals ; Anthozoa/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Germany ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/analogs & derivatives/chemistry ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-negative, rod-shaped, strictly aerobic, and orange-yellow pigmented bacterium, designated strain AFPH31T, was isolated from internal tissues of the scleractinian coral Pocillopora damicornis, cultured in a marine aquarium system at the Justus Liebig University Giessen, Germany. Phylogenetic analyses based on 16S rRNA gene sequences placed the strain within the monophyletic cluster of the genus Winogradskyella and showed highest sequence similarity to type strains of the species Winogradskyella eximia (96.6 %), Winogradskyella wandonensis (96.4 %), and Winogradskyella damuponensis (96.4 %). The strain grew well at 15-37 °C (optimum 25 °C), in the presence of 0.5-8.5 % NaCl (optimum 2 %), and at pH 5.5-8.5 (optimum pH 6.0-7.5). The major cellular fatty acids of strain AFPH31T were iso-C15 : 0 (22.0 %), iso-C15 : 1 G (16.9 %), iso-C17 : 0 3-OH (14.9 %), and anteiso-C15 : 0 (11.9 %). The major compound in the polyamine pattern was sym-homospermidine. The quinone system contained predominantly menaquinone MK-6. The polar lipid profile contained predominantly phosphatidylethanolamine, one unidentified aminolipid, and two unidentified lipids lacking a functional group. The genomic DNA G+C content was 36.8 mol%. According to the phylogenetic, chemotaxonomic, and phenotypic analyses we propose a novel species of the genus Winogradskyella named Winogradskyella pocilloporae sp. nov. The type strain is AFPH31T (=CCM 8816T=CIP 111546T).}, } @article {pmid29620492, year = {2018}, author = {Safronova, VI and Sazanova, AL and Kuznetsova, IG and Belimov, AA and Andronov, EE and Chirak, ER and Popova, JP and Verkhozina, AV and Willems, A and Tikhonovich, IA}, title = {Phyllobacterium zundukense sp. nov., a novel species of rhizobia isolated from root nodules of the legume species Oxytropis triphylla (Pall.) Pers.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1644-1651}, doi = {10.1099/ijsem.0.002722}, pmid = {29620492}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Oxytropis/*microbiology ; Phyllobacteriaceae/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/*microbiology ; Russia ; Sequence Analysis, DNA ; Symbiosis ; }, abstract = {Gram-negative strains Tri-36, Tri-38, Tri-48T and Tri-53 were isolated from root nodules of the relict legume Oxytropis triphylla (Pall.) Pers. originating from Zunduk Cape (Baikal Lake region, Russia). 16S rRNA gene sequencing showed that the novel isolates were phylogenetically closest to the type strains Phyllobacterium sophorae LMG 27899T, Phyllobacterium brassicacearum LMG 22836T, Phyllobacterium endophyticum LMG 26470T and Phyllobacterium bourgognense LMG 22837T while similarity levels between the isolates and the most closely related strain P. endophyticum LMG 26470T were 98.8-99.5 %. The recA and glnII genes of the isolates showed highest sequence similarities with P. sophorae LMG 27899T (95.4 and 89.5 %, respectively) and P. brassicacearum LMG 22836T (91.4 and 85.1 %, respectively). Comparative analysis of phenotypic properties between the novel isolates and the closest reference strains P. sophorae LMG 27899T, P. brassicacearum LMG 22836T and P. endophyticum LMG 26470T was performed using a microassay system. Average nucleotide identities between the whole genome sequences of the isolates Tri-38 and Tri-48T and P. sophorae LMG 27899T, P. brassicacearum LMG 22836T and P. endophyticum LMG 26470T ranged from 79.23 % for P. endophyticum LMG 26470T to 85.74 % for P. sophorae LMG 27899T. The common nodABC genes required for legume nodulation were absent from strains Tri-38 and Tri-48T, although some other symbiotic nod and fix genes were detected. On the basis of genotypic and phenotypic analysis, a novel species, Phyllobacterium zundukense sp. nov. (type strain Tri-48T=LMG 30371T=RCAM 03910T), is proposed.}, } @article {pmid29620491, year = {2018}, author = {Yang, S and Li, M and Lai, Q and Li, G and Shao, Z}, title = {Alcanivorax mobilis sp. nov., a new hydrocarbon-degrading bacterium isolated from deep-sea sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1639-1643}, doi = {10.1099/ijsem.0.002612}, pmid = {29620491}, issn = {1466-5034}, mesh = {Alcanivoraceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Hydrocarbons/metabolism ; Indian Ocean ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salinity ; Seawater/*microbiology ; Sequence Analysis, DNA ; Temperature ; }, abstract = {A taxonomic study was carried out on strain MT13131T, which was isolated from deep-sea sediment of the Indian Ocean during the screening of oil-degrading bacteria. The chain length range of n-alkanes (C8 to C32) oxidized by strain MT13131T was determined in this study. The bacterium was Gram-negative, oxidase- and catalase-positive, single rod shaped, and motile by peritrichous flagella. Growth was observed at salinities of 1-12 % and at temperatures of 10-42 °C. The isolate was capable of Tween 20, 40 and 80 hydrolysis, but incapable of gelatin, cellulose or starch hydrolysis. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain MT13131T belonged to the genus Alcanivorax, with highest sequence similarity to Alcanivorax marinus R8-12T (96.92 %), other species of genus Alcanivorax shared 92.96-96.69 % sequence similarity. The principal fatty acids were summed feature 3 (C16 : 1ω6c/ω7c), summed feature 8 (C18 : 1ω7c/ω6c), C16 : 0 and C12 : 0 3OH. The G+C content of the chromosomal DNA was 64.2 mol%. Phosphatidylglycerol, phosphatidylethanolamine, three aminolipids and three phospholipids were present. The combined genotypic and phenotypic data showed that strain MT13131T represents a novel species within the genus Alcanivorax, for which the name Alcanivorax mobilis sp. nov. is proposed, with the type strain MT13131T (=MCCC 1A11581T=KCTC 52985T).}, } @article {pmid29618821, year = {2018}, author = {Steinbauer, MJ and Grytnes, JA and Jurasinski, G and Kulonen, A and Lenoir, J and Pauli, H and Rixen, C and Winkler, M and Bardy-Durchhalter, M and Barni, E and Bjorkman, AD and Breiner, FT and Burg, S and Czortek, P and Dawes, MA and Delimat, A and Dullinger, S and Erschbamer, B and Felde, VA and Fernández-Arberas, O and Fossheim, KF and Gómez-García, D and Georges, D and Grindrud, ET and Haider, S and Haugum, SV and Henriksen, H and Herreros, MJ and Jaroszewicz, B and Jaroszynska, F and Kanka, R and Kapfer, J and Klanderud, K and Kühn, I and Lamprecht, A and Matteodo, M and di Cella, UM and Normand, S and Odland, A and Olsen, SL and Palacio, S and Petey, M and Piscová, V and Sedlakova, B and Steinbauer, K and Stöckli, V and Svenning, JC and Teppa, G and Theurillat, JP and Vittoz, P and Woodin, SJ and Zimmermann, NE and Wipf, S}, title = {Accelerated increase in plant species richness on mountain summits is linked to warming.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {231-234}, doi = {10.1038/s41586-018-0005-6}, pmid = {29618821}, issn = {1476-4687}, mesh = {*Altitude ; *Biodiversity ; Europe ; *Geographic Mapping ; Global Warming/*statistics & numerical data ; History, 20th Century ; History, 21st Century ; Plants/*classification ; Temperature ; }, abstract = {Globally accelerating trends in societal development and human environmental impacts since the mid-twentieth century 1-7 are known as the Great Acceleration and have been discussed as a key indicator of the onset of the Anthropocene epoch 6 . While reports on ecological responses (for example, changes in species range or local extinctions) to the Great Acceleration are multiplying 8, 9 , it is unknown whether such biotic responses are undergoing a similar acceleration over time. This knowledge gap stems from the limited availability of time series data on biodiversity changes across large temporal and geographical extents. Here we use a dataset of repeated plant surveys from 302 mountain summits across Europe, spanning 145 years of observation, to assess the temporal trajectory of mountain biodiversity changes as a globally coherent imprint of the Anthropocene. We find a continent-wide acceleration in the rate of increase in plant species richness, with five times as much species enrichment between 2007 and 2016 as fifty years ago, between 1957 and 1966. This acceleration is strikingly synchronized with accelerated global warming and is not linked to alternative global change drivers. The accelerating increases in species richness on mountain summits across this broad spatial extent demonstrate that acceleration in climate-induced biotic change is occurring even in remote places on Earth, with potentially far-ranging consequences not only for biodiversity, but also for ecosystem functioning and services.}, } @article {pmid29618820, year = {2018}, author = {Ahmadi, M and Alves, BXR and Baker, CJ and Bertsche, W and Capra, A and Carruth, C and Cesar, CL and Charlton, M and Cohen, S and Collister, R and Eriksson, S and Evans, A and Evetts, N and Fajans, J and Friesen, T and Fujiwara, MC and Gill, DR and Hangst, JS and Hardy, WN and Hayden, ME and Isaac, CA and Johnson, MA and Jones, JM and Jones, SA and Jonsell, S and Khramov, A and Knapp, P and Kurchaninov, L and Madsen, N and Maxwell, D and McKenna, JTK and Menary, S and Momose, T and Munich, JJ and Olchanski, K and Olin, A and Pusa, P and Rasmussen, CØ and Robicheaux, F and Sacramento, RL and Sameed, M and Sarid, E and Silveira, DM and Stutter, G and So, C and Tharp, TD and Thompson, RI and van der Werf, DP and Wurtele, JS}, title = {Characterization of the 1S-2S transition in antihydrogen.}, journal = {Nature}, volume = {557}, number = {7703}, pages = {71-75}, doi = {10.1038/s41586-018-0017-2}, pmid = {29618820}, issn = {1476-4687}, abstract = {In 1928, Dirac published an equation 1 that combined quantum mechanics and special relativity. Negative-energy solutions to this equation, rather than being unphysical as initially thought, represented a class of hitherto unobserved and unimagined particles-antimatter. The existence of particles of antimatter was confirmed with the discovery of the positron 2 (or anti-electron) by Anderson in 1932, but it is still unknown why matter, rather than antimatter, survived after the Big Bang. As a result, experimental studies of antimatter3-7, including tests of fundamental symmetries such as charge-parity and charge-parity-time, and searches for evidence of primordial antimatter, such as antihelium nuclei, have high priority in contemporary physics research. The fundamental role of the hydrogen atom in the evolution of the Universe and in the historical development of our understanding of quantum physics makes its antimatter counterpart-the antihydrogen atom-of particular interest. Current standard-model physics requires that hydrogen and antihydrogen have the same energy levels and spectral lines. The laser-driven 1S-2S transition was recently observed 8 in antihydrogen. Here we characterize one of the hyperfine components of this transition using magnetically trapped atoms of antihydrogen and compare it to model calculations for hydrogen in our apparatus. We find that the shape of the spectral line agrees very well with that expected for hydrogen and that the resonance frequency agrees with that in hydrogen to about 5 kilohertz out of 2.5 × 1015 hertz. This is consistent with charge-parity-time invariance at a relative precision of 2 × 10-12-two orders of magnitude more precise than the previous determination 8 -corresponding to an absolute energy sensitivity of 2 × 10-20 GeV.}, } @article {pmid29618819, year = {2018}, author = {Ronaldson-Bouchard, K and Ma, SP and Yeager, K and Chen, T and Song, L and Sirabella, D and Morikawa, K and Teles, D and Yazawa, M and Vunjak-Novakovic, G}, title = {Advanced maturation of human cardiac tissue grown from pluripotent stem cells.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {239-243}, pmid = {29618819}, issn = {1476-4687}, support = {UH2 EB017103/EB/NIBIB NIH HHS/United States ; R01 HL138486/HL/NHLBI NIH HHS/United States ; R01 HL076485/HL/NHLBI NIH HHS/United States ; UG3 EB025765/EB/NIBIB NIH HHS/United States ; UH3 EB017103/EB/NIBIB NIH HHS/United States ; P41 EB002520/EB/NIBIB NIH HHS/United States ; }, mesh = {Adult ; Calcium/metabolism ; *Cell Differentiation/genetics ; Energy Metabolism/drug effects ; Heart/drug effects/*growth & development ; Humans ; Induced Pluripotent Stem Cells/*cytology ; Isoproterenol/pharmacology ; Mitochondria/metabolism ; Myocardium/*cytology ; Myocytes, Cardiac/*cytology/drug effects/metabolism/ultrastructure ; Sarcomeres/metabolism ; *Tissue Culture Techniques ; Transcriptome ; }, abstract = {Cardiac tissues generated from human induced pluripotent stem cells (iPSCs) can serve as platforms for patient-specific studies of physiology and disease1-6. However, the predictive power of these models is presently limited by the immature state of the cells1, 2, 5, 6. Here we show that this fundamental limitation can be overcome if cardiac tissues are formed from early-stage iPSC-derived cardiomyocytes soon after the initiation of spontaneous contractions and are subjected to physical conditioning with increasing intensity over time. After only four weeks of culture, for all iPSC lines studied, such tissues displayed adult-like gene expression profiles, remarkably organized ultrastructure, physiological sarcomere length (2.2 µm) and density of mitochondria (30%), the presence of transverse tubules, oxidative metabolism, a positive force-frequency relationship and functional calcium handling. Electromechanical properties developed more slowly and did not achieve the stage of maturity seen in adult human myocardium. Tissue maturity was necessary for achieving physiological responses to isoproterenol and recapitulating pathological hypertrophy, supporting the utility of this tissue model for studies of cardiac development and disease.}, } @article {pmid29618818, year = {2018}, author = {Qian, P and Siebert, CA and Wang, P and Canniffe, DP and Hunter, CN}, title = {Cryo-EM structure of the Blastochloris viridis LH1-RC complex at 2.9 Å.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {203-208}, doi = {10.1038/s41586-018-0014-5}, pmid = {29618818}, issn = {1476-4687}, mesh = {Apoproteins/chemistry/metabolism/ultrastructure ; Bacterial Proteins/*chemistry/metabolism/*ultrastructure ; Bacteriochlorophylls/chemistry/metabolism ; Benzoquinones/metabolism ; Binding Sites ; *Cryoelectron Microscopy ; Hyphomicrobiaceae/*chemistry ; Light-Harvesting Protein Complexes/*chemistry/metabolism/*ultrastructure ; Magnesium/chemistry/metabolism ; Models, Molecular ; Photosynthesis ; Protein Conformation ; Protein Stability ; }, abstract = {The light-harvesting 1-reaction centre (LH1-RC) complex is a key functional component of bacterial photosynthesis. Here we present a 2.9 Å resolution cryo-electron microscopy structure of the bacteriochlorophyll b-based LH1-RC complex from Blastochloris viridis that reveals the structural basis for absorption of infrared light and the molecular mechanism of quinone migration across the LH1 complex. The triple-ring LH1 complex comprises a circular array of 17 β-polypeptides sandwiched between 17 α- and 16 γ-polypeptides. Tight packing of the γ-apoproteins between β-polypeptides collectively interlocks and stabilizes the LH1 structure; this, together with the short Mg-Mg distances of bacteriochlorophyll b pairs, contributes to the large redshift of bacteriochlorophyll b absorption. The 'missing' 17th γ-polypeptide creates a pore in the LH1 ring, and an adjacent binding pocket provides a folding template for a quinone, Q P, which adopts a compact, export-ready conformation before passage through the pore and eventual diffusion to the cytochrome bc 1 complex.}, } @article {pmid29618817, year = {2018}, author = {Zhou, P and Fan, H and Lan, T and Yang, XL and Shi, WF and Zhang, W and Zhu, Y and Zhang, YW and Xie, QM and Mani, S and Zheng, XS and Li, B and Li, JM and Guo, H and Pei, GQ and An, XP and Chen, JW and Zhou, L and Mai, KJ and Wu, ZX and Li, D and Anderson, DE and Zhang, LB and Li, SY and Mi, ZQ and He, TT and Cong, F and Guo, PJ and Huang, R and Luo, Y and Liu, XL and Chen, J and Huang, Y and Sun, Q and Zhang, XL and Wang, YY and Xing, SZ and Chen, YS and Sun, Y and Li, J and Daszak, P and Wang, LF and Shi, ZL and Tong, YG and Ma, JY}, title = {Fatal swine acute diarrhoea syndrome caused by an HKU2-related coronavirus of bat origin.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {255-258}, doi = {10.1038/s41586-018-0010-9}, pmid = {29618817}, issn = {1476-4687}, support = {R01 AI110964/AI/NIAID NIH HHS/United States ; }, mesh = {Alphacoronavirus/classification/genetics/*isolation & purification/*pathogenicity ; Animal Diseases/*epidemiology/transmission/*virology ; Animals ; Biodiversity ; China/epidemiology ; Chiroptera/*virology ; Coronavirus Infections/epidemiology/transmission/*veterinary ; Diarrhea/pathology/*veterinary/virology ; Disease Reservoirs/veterinary/virology ; Genome, Viral/genetics ; Humans ; Jejunum/pathology/virology ; Phylogeny ; Severe Acute Respiratory Syndrome/epidemiology/veterinary/virology ; Spatio-Temporal Analysis ; Swine/*virology ; Zoonoses/epidemiology/transmission/virology ; }, abstract = {Cross-species transmission of viruses from wildlife animal reservoirs poses a marked threat to human and animal health 1 . Bats have been recognized as one of the most important reservoirs for emerging viruses and the transmission of a coronavirus that originated in bats to humans via intermediate hosts was responsible for the high-impact emerging zoonosis, severe acute respiratory syndrome (SARS) 2-10 . Here we provide virological, epidemiological, evolutionary and experimental evidence that a novel HKU2-related bat coronavirus, swine acute diarrhoea syndrome coronavirus (SADS-CoV), is the aetiological agent that was responsible for a large-scale outbreak of fatal disease in pigs in China that has caused the death of 24,693 piglets across four farms. Notably, the outbreak began in Guangdong province in the vicinity of the origin of the SARS pandemic. Furthermore, we identified SADS-related CoVs with 96-98% sequence identity in 9.8% (58 out of 591) of anal swabs collected from bats in Guangdong province during 2013-2016, predominantly in horseshoe bats (Rhinolophus spp.) that are known reservoirs of SARS-related CoVs. We found that there were striking similarities between the SADS and SARS outbreaks in geographical, temporal, ecological and aetiological settings. This study highlights the importance of identifying coronavirus diversity and distribution in bats to mitigate future outbreaks that could threaten livestock, public health and economic growth.}, } @article {pmid29618816, year = {2018}, author = {Shi, M and Lin, XD and Chen, X and Tian, JH and Chen, LJ and Li, K and Wang, W and Eden, JS and Shen, JJ and Liu, L and Holmes, EC and Zhang, YZ}, title = {The evolutionary history of vertebrate RNA viruses.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {197-202}, doi = {10.1038/s41586-018-0012-7}, pmid = {29618816}, issn = {1476-4687}, mesh = {Amphibians/virology ; Animals ; Biodiversity ; *Evolution, Molecular ; Fishes/virology ; Genome, Viral/genetics ; Host-Pathogen Interactions ; *Phylogeny ; RNA Viruses/*classification/genetics/*isolation & purification ; Reptiles/virology ; Transcriptome ; Vertebrates/*classification/*virology ; }, abstract = {Our understanding of the diversity and evolution of vertebrate RNA viruses is largely limited to those found in mammalian and avian hosts and associated with overt disease. Here, using a large-scale meta-transcriptomic approach, we discover 214 vertebrate-associated viruses in reptiles, amphibians, lungfish, ray-finned fish, cartilaginous fish and jawless fish. The newly discovered viruses appear in every family or genus of RNA virus associated with vertebrate infection, including those containing human pathogens such as influenza virus, the Arenaviridae and Filoviridae families, and have branching orders that broadly reflected the phylogenetic history of their hosts. We establish a long evolutionary history for most groups of vertebrate RNA virus, and support this by evaluating evolutionary timescales using dated orthologous endogenous virus elements. We also identify new vertebrate-specific RNA viruses and genome architectures, and re-evaluate the evolution of vector-borne RNA viruses. In summary, this study reveals diverse virus-host associations across the entire evolutionary history of the vertebrates.}, } @article {pmid29618815, year = {2018}, author = {Lin, S and Nascimento, EM and Gajera, CR and Chen, L and Neuhöfer, P and Garbuzov, A and Wang, S and Artandi, SE}, title = {Distributed hepatocytes expressing telomerase repopulate the liver in homeostasis and injury.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {244-248}, pmid = {29618815}, issn = {1476-4687}, support = {P30 NS069375/NS/NINDS NIH HHS/United States ; R01 AG056575/AG/NIA NIH HHS/United States ; R35 CA197563/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Lineage/genetics ; Cell Self Renewal/genetics ; Female ; Hepatocytes/*cytology/*enzymology/metabolism ; *Homeostasis/genetics ; Liver/*cytology/*injuries/metabolism/pathology ; *Liver Regeneration/genetics ; Male ; Mice ; Sequence Analysis, RNA ; Telomerase/genetics/*metabolism ; }, abstract = {Hepatocytes are replenished gradually during homeostasis and robustly after liver injury1, 2. In adults, new hepatocytes originate from the existing hepatocyte pool3-8, but the cellular source of renewing hepatocytes remains unclear. Telomerase is expressed in many stem cell populations, and mutations in telomerase pathway genes have been linked to liver diseases9-11. Here we identify a subset of hepatocytes that expresses high levels of telomerase and show that this hepatocyte subset repopulates the liver during homeostasis and injury. Using lineage tracing from the telomerase reverse transcriptase (Tert) locus in mice, we demonstrate that rare hepatocytes with high telomerase expression (TERTHigh hepatocytes) are distributed throughout the liver lobule. During homeostasis, these cells regenerate hepatocytes in all lobular zones, and both self-renew and differentiate to yield expanding hepatocyte clones that eventually dominate the liver. In response to injury, the repopulating activity of TERTHigh hepatocytes is accelerated and their progeny cross zonal boundaries. RNA sequencing shows that metabolic genes are downregulated in TERTHigh hepatocytes, indicating that metabolic activity and repopulating activity may be segregated within the hepatocyte lineage. Genetic ablation of TERTHigh hepatocytes combined with chemical injury causes a marked increase in stellate cell activation and fibrosis. These results provide support for a 'distributed model' of hepatocyte renewal in which a subset of hepatocytes dispersed throughout the lobule clonally expands to maintain liver mass.}, } @article {pmid29618814, year = {2018}, author = {Yu, LJ and Suga, M and Wang-Otomo, ZY and Shen, JR}, title = {Structure of photosynthetic LH1-RC supercomplex at 1.9 Å resolution.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {209-213}, doi = {10.1038/s41586-018-0002-9}, pmid = {29618814}, issn = {1476-4687}, mesh = {Benzoquinones/metabolism ; Binding Sites ; Calcium/metabolism ; Chromatiaceae/*chemistry/metabolism ; Crystallography, X-Ray ; Light-Harvesting Protein Complexes/*chemistry/*metabolism ; Lipids ; Models, Molecular ; *Photosynthesis ; Protein Binding ; Protein Subunits/chemistry/metabolism ; }, abstract = {Light-harvesting complex 1 (LH1) and the reaction centre (RC) form a membrane-protein supercomplex that performs the primary reactions of photosynthesis in purple photosynthetic bacteria. The structure of the LH1-RC complex can provide information on the arrangement of protein subunits and cofactors; however, so far it has been resolved only at a relatively low resolution. Here we report the crystal structure of the calcium-ion-bound LH1-RC supercomplex of Thermochromatium tepidum at a resolution of 1.9 Å. This atomic-resolution structure revealed several new features about the organization of protein subunits and cofactors. We describe the loop regions of RC in their intact states, the interaction of these loop regions with the LH1 subunits, the exchange route for the bound quinone QB with free quinone molecules, the transport of free quinones between the inside and outside of the LH1 ring structure, and the detailed calcium-ion-binding environment. This structure provides a solid basis for the detailed examination of the light reactions that occur during bacterial photosynthesis.}, } @article {pmid29618813, year = {2018}, author = {Abe, K and Irie, K and Nakanishi, H and Suzuki, H and Fujiyoshi, Y}, title = {Crystal structures of the gastric proton pump.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {214-218}, doi = {10.1038/s41586-018-0003-8}, pmid = {29618813}, issn = {1476-4687}, mesh = {Amino Acid Sequence ; Animals ; Binding Sites ; Cations, Monovalent/metabolism ; Crystallography, X-Ray ; H(+)-K(+)-Exchanging ATPase/*chemistry ; HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; Imidazoles/chemistry/pharmacology ; Models, Molecular ; Potassium/metabolism ; Protein Binding ; Proton Pump Inhibitors/chemistry/pharmacology ; Protons ; Pyrroles/chemistry/pharmacology ; Rabbits ; Stomach/*enzymology ; Sulfonamides/chemistry/pharmacology ; Swine ; }, abstract = {The gastric proton pump-the H+, K+-ATPase-is a P-type ATPase responsible for acidifying the gastric juice down to pH 1. This corresponds to a million-fold proton gradient across the membrane of the parietal cell, the steepest known cation gradient of any mammalian tissue. The H+, K+-ATPase is an important target for drugs that treat gastric acid-related diseases. Here we present crystal structures of the H+, K+-ATPase in complex with two blockers, vonoprazan and SCH28080, in the luminal-open state, at 2.8 Å resolution. The drugs have partially overlapping but clearly distinct binding modes in the middle of a conduit running from the gastric lumen to the cation-binding site. The crystal structures suggest that the tight configuration at the cation-binding site lowers the pK a value of Glu820 sufficiently to enable the release of a proton even into the pH 1 environment of the stomach.}, } @article {pmid29618812, year = {2018}, author = {Takahashi, F and Suzuki, T and Osakabe, Y and Betsuyaku, S and Kondo, Y and Dohmae, N and Fukuda, H and Yamaguchi-Shinozaki, K and Shinozaki, K}, title = {A small peptide modulates stomatal control via abscisic acid in long-distance signalling.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {235-238}, doi = {10.1038/s41586-018-0009-2}, pmid = {29618812}, issn = {1476-4687}, mesh = {Abscisic Acid/biosynthesis/*metabolism ; Arabidopsis/*metabolism ; Arabidopsis Proteins/metabolism ; CRISPR-Cas Systems ; Dehydration ; Dioxygenases/metabolism ; Gene Expression Regulation ; Intercellular Signaling Peptides and Proteins/metabolism ; Mutation ; Plant Leaves/metabolism ; Plant Proteins/metabolism ; Plant Roots/metabolism ; Plant Stomata/*metabolism ; Protein-Serine-Threonine Kinases/metabolism ; *Signal Transduction ; Water/metabolism ; }, abstract = {Mammalian peptide hormones propagate extracellular stimuli from sensing tissues to appropriate targets to achieve optimal growth maintenance 1 . In land plants, root-to-shoot signalling is important to prevent water loss by transpiration and to adapt to water-deficient conditions 2, 3 . The phytohormone abscisic acid has a role in the regulation of stomatal movement to prevent water loss 4 . However, no mobile signalling molecules have yet been identified that can trigger abscisic acid accumulation in leaves. Here we show that the CLAVATA3/EMBRYO-SURROUNDING REGION-RELATED 25 (CLE25) peptide transmits water-deficiency signals through vascular tissues in Arabidopsis, and affects abscisic acid biosynthesis and stomatal control of transpiration in association with BARELY ANY MERISTEM (BAM) receptors in leaves. The CLE25 gene is expressed in vascular tissues and enhanced in roots in response to dehydration stress. The root-derived CLE25 peptide moves from the roots to the leaves, where it induces stomatal closure by modulating abscisic acid accumulation and thereby enhances resistance to dehydration stress. BAM receptors are required for the CLE25 peptide-induced dehydration stress response in leaves, and the CLE25-BAM module therefore probably functions as one of the signalling molecules for long-distance signalling in the dehydration response.}, } @article {pmid29618615, year = {2018}, author = {Goldbogen, JA}, title = {Physiological constraints on marine mammal body size.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {3995-3997}, pmid = {29618615}, issn = {1091-6490}, mesh = {Animals ; *Body Size ; *Mammals ; }, } @article {pmid29618614, year = {2018}, author = {Han, YL and Ronceray, P and Xu, G and Malandrino, A and Kamm, RD and Lenz, M and Broedersz, CP and Guo, M}, title = {Cell contraction induces long-ranged stress stiffening in the extracellular matrix.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4075-4080}, pmid = {29618614}, issn = {1091-6490}, support = {677532//European Research Council/International ; U01 CA202123/CA/NCI NIH HHS/United States ; }, mesh = {Cell Culture Techniques/instrumentation ; Cell Line ; Cell Line, Tumor ; *Cell Shape ; Collagen/chemistry ; Computer Simulation ; Cytochalasin D/pharmacology ; Drug Combinations ; Elasticity ; Epithelial Cells/physiology/ultrastructure ; Extracellular Matrix/chemistry/*ultrastructure ; Extracellular Matrix Proteins/*chemistry ; Fibrin/chemistry ; Humans ; Laminin/chemistry ; Models, Biological ; Motion ; Optical Tweezers ; Proteoglycans/chemistry ; Rheology/methods ; Stress, Mechanical ; }, abstract = {Animal cells in tissues are supported by biopolymer matrices, which typically exhibit highly nonlinear mechanical properties. While the linear elasticity of the matrix can significantly impact cell mechanics and functionality, it remains largely unknown how cells, in turn, affect the nonlinear mechanics of their surrounding matrix. Here, we show that living contractile cells are able to generate a massive stiffness gradient in three distinct 3D extracellular matrix model systems: collagen, fibrin, and Matrigel. We decipher this remarkable behavior by introducing nonlinear stress inference microscopy (NSIM), a technique to infer stress fields in a 3D matrix from nonlinear microrheology measurements with optical tweezers. Using NSIM and simulations, we reveal large long-ranged cell-generated stresses capable of buckling filaments in the matrix. These stresses give rise to the large spatial extent of the observed cell-induced matrix stiffness gradient, which can provide a mechanism for mechanical communication between cells.}, } @article {pmid29618613, year = {2018}, author = {Trinkaus, E}, title = {The labyrinth of human variation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {3992-3994}, pmid = {29618613}, issn = {1091-6490}, mesh = {Ear, Inner/*anatomy & histology ; *Human Migration ; Humans ; }, } @article {pmid29618612, year = {2018}, author = {Fan, Y and Liu, W and Bi, R and Densmore, MJ and Sato, T and Mannstadt, M and Yuan, Q and Zhou, X and Olauson, H and Larsson, TE and Toka, HR and Pollak, MR and Brown, EM and Lanske, B}, title = {Interrelated role of Klotho and calcium-sensing receptor in parathyroid hormone synthesis and parathyroid hyperplasia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3749-E3758}, pmid = {29618612}, issn = {1091-6490}, support = {R01 DK097105/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bone and Bones/pathology ; Calcium/metabolism ; Calcium, Dietary/administration & dosage ; Female ; Glucuronidase/deficiency/genetics/*physiology ; Homeostasis ; Hypercalcemia/genetics/pathology ; Hyperparathyroidism/genetics/pathology ; Hyperplasia ; Hypocalcemia/metabolism ; Hypophosphatemia/genetics/pathology ; Immunoprecipitation ; Kidney/pathology ; Male ; Mice ; Parathyroid Glands/*metabolism/pathology ; Parathyroid Hormone/*biosynthesis/genetics ; Protein Interaction Mapping ; RNA, Messenger/biosynthesis/genetics ; Receptors, G-Protein-Coupled/deficiency/genetics/*physiology ; }, abstract = {The pathogenesis of parathyroid gland hyperplasia is poorly understood, and a better understanding is essential if there is to be improvement over the current strategies for prevention and treatment of secondary hyperparathyroidism. Here we investigate the specific role of Klotho expressed in the parathyroid glands (PTGs) in mediating parathyroid hormone (PTH) and serum calcium homeostasis, as well as the potential interaction between calcium-sensing receptor (CaSR) and Klotho. We generated mouse strains with PTG-specific deletion of Klotho and CaSR and dual deletion of both genes. We show that ablating CaSR in the PTGs increases PTH synthesis, that Klotho has a pivotal role in suppressing PTH in the absence of CaSR, and that CaSR together with Klotho regulates PTH biosynthesis and PTG growth. We utilized the tdTomato gene in our mice to visualize and collect PTGs to reveal an inhibitory function of Klotho on PTG cell proliferation. Chronic hypocalcemia and ex vivo PTG culture demonstrated an independent role for Klotho in mediating PTH secretion. Moreover, we identify an interaction between PTG-expressed CaSR and Klotho. These findings reveal essential and interrelated functions for CaSR and Klotho during parathyroid hyperplasia.}, } @article {pmid29618611, year = {2018}, author = {Tanaka, KI and Xue, Y and Nguyen-Yamamoto, L and Morris, JA and Kanazawa, I and Sugimoto, T and Wing, SS and Richards, JB and Goltzman, D}, title = {FAM210A is a novel determinant of bone and muscle structure and strength.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3759-E3768}, pmid = {29618611}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Adult ; Animals ; Body Weight/*genetics ; Bone Density/*genetics ; Cells, Cultured ; Child ; Female ; Gene Expression Profiling ; Genes, Lethal ; Genes, Reporter ; Hand Strength ; Humans ; Male ; Mice ; Mice, Knockout ; Mitochondria, Muscle/*metabolism ; Mitochondrial Proteins/*genetics ; Muscle Strength/physiology ; Muscle, Skeletal/metabolism/pathology ; Myoblasts/metabolism ; Organ Specificity ; Osteoblasts/metabolism ; Osteoclasts/metabolism ; Osteoporosis/genetics/*metabolism ; Phenotype ; Polymorphism, Single Nucleotide ; Sarcopenia/genetics/*metabolism ; Weight-Bearing ; }, abstract = {Osteoporosis and sarcopenia are common comorbid diseases, yet their shared mechanisms are largely unknown. We found that genetic variation near FAM210A was associated, through large genome-wide association studies, with fracture, bone mineral density (BMD), and appendicular and whole body lean mass, in humans. In mice, Fam210a was expressed in muscle mitochondria and cytoplasm, as well as in heart and brain, but not in bone. Grip strength and limb lean mass were reduced in tamoxifen-inducible Fam210a homozygous global knockout mice (TFam210a-/-), and in tamoxifen-inducible Fam210 skeletal muscle cell-specific knockout mice (TFam210aMus-/-). Decreased BMD, bone biomechanical strength, and bone formation, and elevated osteoclast activity with microarchitectural deterioration of trabecular and cortical bones, were observed in TFam210a-/- mice. BMD of male TFam210aMus-/- mice was also reduced, and osteoclast numbers and surface in TFam210aMus-/- mice increased. Microarray analysis of muscle cells from TFam210aMus-/- mice identified candidate musculoskeletal modulators. FAM210A, a novel gene, therefore has a crucial role in regulating bone structure and function, and may impact osteoporosis through a biological pathway involving muscle as well as through other mechanisms.}, } @article {pmid29618610, year = {2018}, author = {Bilbao, A and Patel, AK and Rahman, M and Vanapalli, SA and Blawzdziewicz, J}, title = {Roll maneuvers are essential for active reorientation of Caenorhabditis elegans in 3D media.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3616-E3625}, pmid = {29618610}, issn = {1091-6490}, support = {R21 AG050503/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*physiology ; Hydrodynamics ; Models, Biological ; Rotation ; Swimming/*physiology ; }, abstract = {Locomotion of the nematode Caenorhabditis elegans is a key observable used in investigations ranging from behavior to neuroscience to aging. However, while the natural environment of this model organism is 3D, quantitative investigations of its locomotion have been mostly limited to 2D motion. Here, we present a quantitative analysis of how the nematode reorients itself in 3D media. We identify a unique behavioral state of C. elegans-a roll maneuver-which is an essential component of 3D locomotion in burrowing and swimming. The rolls, associated with nonzero torsion of the nematode body, result in rotation of the plane of dorsoventral body undulations about the symmetry axis of the trajectory. When combined with planar turns in a new undulation plane, the rolls allow the nematode to reorient its body in any direction, thus enabling complete exploration of 3D space. The rolls observed in swimming are much faster than the ones in burrowing; we show that this difference stems from a purely hydrodynamic enhancement mechanism and not from a gait change or an increase in the body torsion. This result demonstrates that hydrodynamic viscous forces can enhance 3D reorientation in undulatory locomotion, in contrast to known hydrodynamic hindrance of both forward motion and planar turns.}, } @article {pmid29618609, year = {2018}, author = {Oemer, G and Lackner, K and Muigg, K and Krumschnabel, G and Watschinger, K and Sailer, S and Lindner, H and Gnaiger, E and Wortmann, SB and Werner, ER and Zschocke, J and Keller, MA}, title = {Molecular structural diversity of mitochondrial cardiolipins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4158-4163}, pmid = {29618609}, issn = {1091-6490}, mesh = {Animals ; Bacteria/chemistry ; Barth Syndrome/metabolism ; Cardiolipins/*chemistry/isolation & purification ; Cell Line ; Chromatography, High Pressure Liquid ; Fatty Acids/analysis ; Fibroblasts/chemistry ; Fungi/chemistry ; Humans ; Membrane Lipids/*chemistry/isolation & purification ; Mice ; Mitochondrial Membranes/*chemistry ; Models, Molecular ; Molecular Structure ; Plants/chemistry ; RAW 264.7 Cells ; Tandem Mass Spectrometry ; Vertebrates/metabolism ; }, abstract = {Current strategies used to quantitatively describe the biological diversity of lipids by mass spectrometry are often limited in assessing the exact structural variability of individual molecular species in detail. A major challenge is represented by the extensive isobaric overlap present among lipids, hampering their accurate identification. This is especially true for cardiolipins, a mitochondria-specific class of phospholipids, which are functionally involved in many cellular functions, including energy metabolism, cristae structure, and apoptosis. Substituted with four fatty acyl side chains, cardiolipins offer a particularly high potential to achieve complex mixtures of molecular species. Here, we demonstrate how systematically generated high-performance liquid chromatography-mass spectral data can be utilized in a mathematical structural modeling approach, to comprehensively analyze and characterize the molecular diversity of mitochondrial cardiolipin compositions in cell culture and disease models, cardiolipin modulation experiments, and a broad variety of frequently studied model organisms.}, } @article {pmid29618382, year = {2018}, author = {Sylvester, B and Gasarasi, DB and Aboud, S and Tarimo, D and Massawe, S and Mpembeni, R and Swedberg, G}, title = {Hyperparasitaemia during clinical malaria episodes in infants aged 0-24 months and its association with in utero exposure to Plasmodium falciparum.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {232}, pmid = {29618382}, issn = {1756-0500}, mesh = {Adult ; *Disease Susceptibility ; Female ; Humans ; Infant ; Infant, Newborn ; Malaria/*blood/epidemiology/*parasitology ; Male ; Parasitemia/*blood/epidemiology ; Placenta/*parasitology ; *Plasmodium falciparum/immunology ; Pregnancy ; Pregnancy Complications, Parasitic/epidemiology/*parasitology ; Prospective Studies ; Tanzania/epidemiology ; }, abstract = {OBJECTIVE: Existing information has shown that infants who are prenatally exposed to P. falciparum are susceptible to subsequent malaria infections. However, the effect of prenatal exposure to P. falciparum on parasite density during clinical malaria episodes has not been fully elucidated. This study is a component of a prospective cohort study for which initial results have been published. This component was designed to determine the effect of prenatal exposure to P. falciparum on parasite density during clinical malaria episodes in the first 24 months of life. A total of 215 infants were involved and monitored for clinical malaria episodes defined by fever (≥ 37 °C) and parasitaemia. The geometric mean parasite counts between exposed and unexposed infants were compared using independent samples t test. The effect of in utero exposure to P. falciparum on parasite density was assessed using binary logistic regression.

RESULTS: The geometric mean parasite count per µl of blood during clinical malaria episodes in exposed infants was 24,889 (95% CI 18,286-31,490) while in unexposed infants it was 14,035 (95% CI 12,111-15,960), P < 0.05. Prenatal exposure to P. falciparum was associated with hyperparasitaemia during clinical malaria episodes (OR 7.04, 95% CI 2.31-21.74), while other factors were not significantly associated (P > 0.05).}, } @article {pmid29618337, year = {2018}, author = {Sabino, M and Carmelo, VAO and Mazzoni, G and Cappelli, K and Capomaccio, S and Ajmone-Marsan, P and Verini-Supplizi, A and Trabalza-Marinucci, M and Kadarmideen, HN}, title = {Gene co-expression networks in liver and muscle transcriptome reveal sex-specific gene expression in lambs fed with a mix of essential oils.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {236}, pmid = {29618337}, issn = {1471-2164}, support = {RB-2015//University of Perugia UNIPG/ ; }, mesh = {Animals ; Dietary Supplements ; Female ; Gene Expression Profiling/*veterinary ; Gene Expression Regulation/drug effects ; *Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing/veterinary ; Liver/*chemistry/drug effects ; Male ; Muscles/*chemistry/drug effects ; Nutrigenomics ; Oils, Volatile/*administration & dosage/pharmacology ; Organ Specificity ; Sequence Analysis, RNA/veterinary ; Sex Factors ; Sheep ; }, abstract = {BACKGROUND: Essential oil (EO) dietary supplementation is a new strategy to improve animal health. EO compounds have antiparasitic, antimicrobial, antiviral, antimycotic, antioxidant and anti-inflammatory proprieties. Nutrigenomics investigations represent innovative approaches in understanding the relation between diet effect and gene expression related to the animal performance. Few nutrigenomics studies have used a high-throughput RNA-Sequencing (RNA-Seq) approach, despite great potential of RNA-Seq data in gene expression quantification and in co-expression network analyses. Our aim is to use the potential of RNA-Sequencing data in order to evaluate the effect of an EO supplementary diet on gene expression in both lamb liver and muscle.

RESULTS: Using a treatment and sex interaction model, 13 and 4 differentially expressed genes were identified in liver and muscle respectively. Sex-specific differentially expressed (DE) genes were identified in both sexes. Using network based analysis, different clusters of co-expressed genes that were highly correlated to the diet were detected in males vs. females, in agreement with DE analysis. A total of five regulatory genes in liver tissue associated to EO diet were identified: DNAJB9, MANF, UFM1, CTNNLA1 and NFX1. Our study reveals a sex-dependent effect of EO diet in both tissues, and an influence on the expression of genes mainly involved in immune, inflammatory and stress pathway.

CONCLUSION: Our analysis suggests a sex-dependent effect of the EO dietary supplementation on the expression profile of both liver and muscle tissues. We hypothesize that the presence of EOs could have beneficial effects on wellness of male lamb and further analyses are needed to understand the biological mechanisms behind the different effect of EO metabolites based on sex. Using lamb as a model for nutrigenomics studies, it could be interesting to investigate the effects of EO diets in other species and in humans.}, } @article {pmid29618324, year = {2018}, author = {Liu, L and Wang, Y and He, P and Li, P and Lee, J and Soltis, DE and Fu, C}, title = {Chloroplast genome analyses and genomic resource development for epilithic sister genera Oresitrophe and Mukdenia (Saxifragaceae), using genome skimming data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {235}, pmid = {29618324}, issn = {1471-2164}, support = {31500184//National Natural Science Foundation of China/ ; 31461123001//NSFC-NSF Dimensions of Biodiversity program/ ; }, mesh = {Ecosystem ; Evolution, Molecular ; Genetic Markers ; Genetics, Population ; *Genome, Chloroplast ; Genome, Plant ; Phylogeny ; Plant Proteins/*genetics ; Saxifragaceae/classification/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Epilithic sister genera Oresitrophe and Mukdenia (Saxifragaceae) have an epilithic habitat (rocky slopes) and a parapatric distribution in East Asia, which makes them an ideal model for a more comprehensive understanding of the demographic and divergence history and the influence of climate changes in East Asia. However, the genetic background and resources for these two genera are scarce.

RESULTS: The complete chloroplast (cp) genomes of two Oresitrophe rupifraga and one Mukdenia rossii individuals were reconstructed and comparative analyses were conducted to examine the evolutionary pattern of chloroplast genomes in Saxifragaceae. The cp genomes ranged from 156,738 bp to 156,960 bp in length and had a typical quadripartite structure with a conserved genome arrangement. Comparative analysis revealed the intron of rpl2 has been lost in Heuchera parviflora, Tiarella polyphylla, M. rossii and O. rupifraga but presents in the reference genome of Penthorum chinense. Seven cp hotspot regions (trnH-psbA, trnR-atpA, atpI-rps2, rps2-rpoC2, petN-psbM, rps4-trnT and rpl33-rps18) were identified between Oresitrophe and Mukdenia, while four hotspots (trnQ-psbK, trnR-atpA, trnS-psbZ and rpl33-rps18) were identified within Oresitrophe. In addition, 24 polymorphic cpSSR loci were found between Oresitrophe and Mukdenia. Most importantly, we successfully developed 126 intergeneric polymorphic gSSR markers between Oresitrophe and Mukdenia, as well as 452 intrageneric ones within Oresitrophe. Twelve randomly selected intergeneric gSSRs have shown that these two genera exhibit a significant genetic structure.

CONCLUSIONS: In this study, we conducted genome skimming for Oresitrophe rupifraga and Mukdenia rossii. Using these data, we were able to not only assemble their complete chloroplast genomes, but also develop abundant genetic resources (cp hotspots, cpSSRs, polymorphic gSSRs). The genomic patterns and genetic resources presented here will contribute to further studies on population genetics, phylogeny and conservation biology in Saxifragaceae.}, } @article {pmid29618320, year = {2018}, author = {Gu, Z and Eils, R and Schlesner, M and Ishaque, N}, title = {EnrichedHeatmap: an R/Bioconductor package for comprehensive visualization of genomic signal associations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {234}, pmid = {29618320}, issn = {1471-2164}, support = {#031A537A, #031A537C//BMBF-funded de.NBI HD-HuB network/ ; }, mesh = {Algorithms ; Genomics/*methods ; Software ; }, } @article {pmid29618319, year = {2018}, author = {Weiß, CL and Pais, M and Cano, LM and Kamoun, S and Burbano, HA}, title = {nQuire: a statistical framework for ploidy estimation using next generation sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {122}, pmid = {29618319}, issn = {1471-2105}, mesh = {*Genome, Fungal ; High-Throughput Nucleotide Sequencing/*methods ; *Ploidies ; Saccharomyces cerevisiae/*genetics ; Sequence Analysis, DNA/*methods ; *Software ; }, abstract = {BACKGROUND: Intraspecific variation in ploidy occurs in a wide range of species including pathogenic and nonpathogenic eukaryotes such as yeasts and oomycetes. Ploidy can be inferred indirectly - without measuring DNA content - from experiments using next-generation sequencing (NGS). We present nQuire, a statistical framework that distinguishes between diploids, triploids and tetraploids using NGS. The command-line tool models the distribution of base frequencies at variable sites using a Gaussian Mixture Model, and uses maximum likelihood to select the most plausible ploidy model. nQuire handles large genomes at high coverage efficiently and uses standard input file formats.

RESULTS: We demonstrate the utility of nQuire analyzing individual samples of the pathogenic oomycete Phytophthora infestans and the Baker's yeast Saccharomyces cerevisiae. Using these organisms we show the dependence between reliability of the ploidy assignment and sequencing depth. Additionally, we employ normalized maximized log- likelihoods generated by nQuire to ascertain ploidy level in a population of samples with ploidy heterogeneity. Using these normalized values we cluster samples in three dimensions using multivariate Gaussian mixtures. The cluster assignments retrieved from a S. cerevisiae population recovered the true ploidy level in over 96% of samples. Finally, we show that nQuire can be used regionally to identify chromosomal aneuploidies.

CONCLUSIONS: nQuire provides a statistical framework to study organisms with intraspecific variation in ploidy. nQuire is likely to be useful in epidemiological studies of pathogens, artificial selection experiments, and for historical or ancient samples where intact nuclei are not preserved. It is implemented as a stand-alone Linux command line tool in the C programming language and is available at https://github.com/clwgg/nQuire under the MIT license.}, } @article {pmid29618318, year = {2018}, author = {Verma, A and Bradford, Y and Dudek, S and Lucas, AM and Verma, SS and Pendergrass, SA and Ritchie, MD}, title = {A simulation study investigating power estimates in phenome-wide association studies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {120}, pmid = {29618318}, issn = {1471-2105}, support = {R01 AI077505/AI/NIAID NIH HHS/United States ; R01 GM111913/GM/NIGMS NIH HHS/United States ; SAP 4100070267//SAP/International ; U01 HG008679/HG/NHGRI NIH HHS/United States ; HG008679/HG/NHGRI NIH HHS/United States ; AI077505/NH/NIH HHS/United States ; GM111913/NH/NIH HHS/United States ; }, mesh = {Algorithms ; *Computer Simulation ; Disease/*genetics ; *Genetic Association Studies ; *Genome-Wide Association Study ; Humans ; *Phenotype ; *Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: Phenome-wide association studies (PheWAS) are a high-throughput approach to evaluate comprehensive associations between genetic variants and a wide range of phenotypic measures. PheWAS has varying sample sizes for quantitative traits, and variable numbers of cases and controls for binary traits across the many phenotypes of interest, which can affect the statistical power to detect associations. The motivation of this study is to investigate the various parameters which affect the estimation of statistical power in PheWAS, including sample size, case-control ratio, minor allele frequency, and disease penetrance.

RESULTS: We performed a PheWAS simulation study, where we investigated variations in statistical power based on different parameters, such as overall sample size, number of cases, case-control ratio, minor allele frequency, and disease penetrance. The simulation was performed on both binary and quantitative phenotypic measures. Our simulation on binary traits suggests that the number of cases has more impact on statistical power than the case to control ratio; also, we found that a sample size of 200 cases or more maintains the statistical power to identify associations for common variants. For quantitative traits, a sample size of 1000 or more individuals performed best in the power calculations. We focused on common genetic variants (MAF > 0.01) in this study; however, in future studies, we will be extending this effort to perform similar simulations on rare variants.

CONCLUSIONS: This study provides a series of PheWAS simulation analyses that can be used to estimate statistical power for some potential scenarios. These results can be used to provide guidelines for appropriate study design for future PheWAS analyses.}, } @article {pmid29618317, year = {2018}, author = {Doyle, JM and Bell, DA and Bloom, PH and Emmons, G and Fesnock, A and Katzner, TE and LaPré, L and Leonard, K and SanMiguel, P and Westerman, R and Andrew DeWoody, J}, title = {New insights into the phylogenetics and population structure of the prairie falcon (Falco mexicanus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {233}, pmid = {29618317}, issn = {1471-2164}, support = {L12AC20102, L11PX02237, L12AC2010//U.S. Bureau of Land Management/ ; University Faculty Scholar program//Provost's Office at Purdue University/ ; PINN645-21//National Park Service/ ; BIO170038//XSEDE/ ; }, mesh = {Animals ; Avian Proteins/*genetics ; California ; Falconiformes/*classification/genetics ; Female ; Genetics, Population ; Idaho ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; *Polymorphism, Single Nucleotide ; Whole Genome Sequencing/*veterinary ; }, abstract = {BACKGROUND: Management requires a robust understanding of between- and within-species genetic variability, however such data are still lacking in many species. For example, although multiple population genetics studies of the peregrine falcon (Falco peregrinus) have been conducted, no similar studies have been done of the closely-related prairie falcon (F. mexicanus) and it is unclear how much genetic variation and population structure exists across the species' range. Furthermore, the phylogenetic relationship of F. mexicanus relative to other falcon species is contested. We utilized a genomics approach (i.e., genome sequencing and assembly followed by single nucleotide polymorphism genotyping) to rapidly address these gaps in knowledge.

RESULTS: We sequenced the genome of a single female prairie falcon and generated a 1.17 Gb (gigabases) draft genome assembly. We generated maximum likelihood phylogenetic trees using complete mitochondrial genomes as well as nuclear protein-coding genes. This process provided evidence that F. mexicanus is an outgroup to the clade that includes the peregrine falcon and members of the subgenus Hierofalco. We annotated > 16,000 genes and almost 600,000 high-quality single nucleotide polymorphisms (SNPs) in the nuclear genome, providing the raw material for a SNP assay design featuring > 140 gene-associated markers and a molecular-sexing marker. We subsequently genotyped ~ 100 individuals from California (including the San Francisco East Bay Area, Pinnacles National Park and the Mojave Desert) and Idaho (Snake River Birds of Prey National Conservation Area). We tested for population structure and found evidence that individuals sampled in California and Idaho represent a single panmictic population.

CONCLUSIONS: Our study illustrates how genomic resources can rapidly shed light on genetic variability in understudied species and resolve phylogenetic relationships. Furthermore, we found evidence of a single, randomly mating population of prairie falcons across our sampling locations. Prairie falcons are highly mobile and relatively rare long-distance dispersal events may promote gene flow throughout the range. As such, California's prairie falcons might be managed as a single population, indicating that management actions undertaken to benefit the species at the local level have the potential to influence the species as a whole.}, } @article {pmid29618316, year = {2018}, author = {Katzman, B and Tang, D and Santella, A and Bao, Z}, title = {AceTree: a major update and case study in the long term maintenance of open-source scientific software.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {121}, pmid = {29618316}, issn = {1471-2105}, support = {R24 OD016474/OD/NIH HHS/United States ; U01 HD075602/HD/NICHD NIH HHS/United States ; R24OD016474/NH/NIH HHS/United States ; GM097576/NH/NIH HHS/United States ; U01 HD075602/NH/NIH HHS/United States ; R01 GM097576/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*embryology ; *Cell Lineage ; Computational Biology/*methods ; Drosophila/*embryology ; Embryo, Nonmammalian/*cytology ; Microscopy, Fluorescence ; Phenotype ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: AceTree, a software application first released in 2006, facilitates exploration, curation and editing of tracked C. elegans nuclei in 4-dimensional (4D) fluorescence microscopy datasets. Since its initial release, AceTree has been continuously used to interact with, edit and interpret C. elegans lineage data. In its 11 year lifetime, AceTree has been periodically updated to meet the technical and research demands of its community of users. This paper presents the newest iteration of AceTree which contains extensive updates, demonstrates the new applicability of AceTree in other developmental contexts, and presents its evolutionary software development paradigm as a viable model for maintaining scientific software.

RESULTS: Large scale updates have been made to the user interface for an improved user experience. Tools have been grouped according to functionality and obsolete methods have been removed. Internal requirements have been changed that enable greater flexibility of use both in C. elegans contexts and in other model organisms. Additionally, the original 3-dimensional (3D) viewing window has been completely reimplemented. The new window provides a new suite of tools for data exploration.

CONCLUSION: By responding to technical advancements and research demands, AceTree has remained a useful tool for scientific research for over a decade. The updates made to the codebase have extended AceTree's applicability beyond its initial use in C. elegans and enabled its usage with other model organisms. The evolution of AceTree demonstrates a viable model for maintaining scientific software over long periods of time.}, } @article {pmid29618315, year = {2018}, author = {Koufariotis, LT and Chen, YP and Stothard, P and Hayes, BJ}, title = {Variance explained by whole genome sequence variants in coding and regulatory genome annotations for six dairy traits.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {237}, pmid = {29618315}, issn = {1471-2164}, mesh = {Animals ; Cattle ; Female ; Fertility ; Gene Frequency ; *Gene Regulatory Networks ; *Genetic Variation ; Molecular Sequence Annotation ; Pregnancy ; *Quantitative Trait Loci ; RNA Splice Sites ; Whole Genome Sequencing/*veterinary ; }, abstract = {BACKGROUND: There are an exceedingly large number of sequence variants discovered through whole genome sequencing in most populations, including cattle. Deciphering which of these affect complex traits is a major challenge. In this study we hypothesize that variants in some functional classes, such as splice site regions, coding regions, DNA methylated regions and long noncoding RNA will explain more variance in complex traits than others. Two variance component approaches were used to test this hypothesis - the first determines if variants in a functional class capture a greater proportion of the variance, than expected by chance, the second uses the proportion of variance explained when variants in all annotations are fitted simultaneously.

RESULTS: Our data set consisted of 28.3 million imputed whole genome sequence variants in 16,581 dairy cattle with records for 6 complex trait phenotypes, including production and fertility. We found that sequence variants in splice site regions and synonymous classes captured the greatest proportion of the variance, explaining up to 50% of the variance across all traits. We also found sequence variants in target sites for DNA methylation (genomic regions that are found be highly methylated in bovine placentas), captured a significant proportion of the variance. Per sequence variant, splice site variants explain the highest proportion of variance in this study. The proportion of variance captured by the missense predicted deleterious (from SIFT) and missense tolerated classes was relatively small.

CONCLUSION: The results demonstrate using functional annotations to filter whole genome sequence variants into more informative subsets could be useful for prioritization of the variants that are more likely to be associated with complex traits. In addition to variants found in splice sites and protein coding genes regulatory variants and those found in DNA methylated regions, explained considerable variation in milk production and fertility traits. In our analysis synonymous variants captured a significant proportion of the variance, which raises the possible explanation that synonymous mutations might have some effects, or more likely that these variants are miss-annotated, or alternatively the results reflect imperfect imputation of the actual causative variants.}, } @article {pmid29618314, year = {2018}, author = {Dobrin, BH and Zwickl, DJ and Sanderson, MJ}, title = {The prevalence of terraced treescapes in analyses of phylogenetic data sets.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {46}, pmid = {29618314}, issn = {1471-2148}, support = {DEB-1353815//National Science Foundation/International ; }, mesh = {*Databases, Genetic ; Genes ; Models, Genetic ; *Phylogeny ; }, abstract = {BACKGROUND: The pattern of data availability in a phylogenetic data set may lead to the formation of terraces, collections of equally optimal trees. Terraces can arise in tree space if trees are scored with parsimony or with partitioned, edge-unlinked maximum likelihood. Theory predicts that terraces can be large, but their prevalence in contemporary data sets has never been surveyed. We selected 26 data sets and phylogenetic trees reported in recent literature and investigated the terraces to which the trees would belong, under a common set of inference assumptions. We examined terrace size as a function of the sampling properties of the data sets, including taxon coverage density (the proportion of taxon-by-gene positions with any data present) and a measure of gene sampling "sufficiency". We evaluated each data set in relation to the theoretical minimum gene sampling depth needed to reduce terrace size to a single tree, and explored the impact of the terraces found in replicate trees in bootstrap methods.

RESULTS: Terraces were identified in nearly all data sets with taxon coverage densities < 0.90. They were not found, however, in high-coverage-density (i.e., ≥ 0.94) transcriptomic and genomic data sets. The terraces could be very large, and size varied inversely with taxon coverage density and with gene sampling sufficiency. Few data sets achieved a theoretical minimum gene sampling depth needed to reduce terrace size to a single tree. Terraces found during bootstrap resampling reduced overall support.

CONCLUSIONS: If certain inference assumptions apply, trees estimated from empirical data sets often belong to large terraces of equally optimal trees. Terrace size correlates to data set sampling properties. Data sets seldom include enough genes to reduce terrace size to one tree. When bootstrap replicate trees lie on a terrace, statistical support for phylogenetic hypotheses may be reduced. Although some of the published analyses surveyed were conducted with edge-linked inference models (which do not induce terraces), unlinked models have been used and advocated. The present study describes the potential impact of that inference assumption on phylogenetic inference in the context of the kinds of multigene data sets now widely assembled for large-scale tree construction.}, } @article {pmid29618097, year = {2018}, author = {Vialle, RA and Tamuri, AU and Goldman, N}, title = {Alignment Modulates Ancestral Sequence Reconstruction Accuracy.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1783-1797}, pmid = {29618097}, issn = {1537-1719}, abstract = {Accurate reconstruction of ancestral states is a critical evolutionary analysis when studying ancient proteins and comparing biochemical properties between parental or extinct species and their extant relatives. It relies on multiple sequence alignment (MSA) which may introduce biases, and it remains unknown how MSA methodological approaches impact ancestral sequence reconstruction (ASR). Here, we investigate how MSA methodology modulates ASR using a simulation study of various evolutionary scenarios. We evaluate the accuracy of ancestral protein sequence reconstruction for simulated data and compare reconstruction outcomes using different alignment methods. Our results reveal biases introduced not only by aligner algorithms and assumptions, but also tree topology and the rate of insertions and deletions. Under many conditions we find no substantial differences between the MSAs. However, increasing the difficulty for the aligners can significantly impact ASR. The MAFFT consistency aligners and PRANK variants exhibit the best performance, whereas FSA displays limited performance. We also discover a bias towards reconstructed sequences longer than the true ancestors, deriving from a preference for inferring insertions, in almost all MSA methodological approaches. In addition, we find measures of MSA quality generally correlate highly with reconstruction accuracy. Thus, we show MSA methodological differences can affect the quality of reconstructions and propose MSA methods should be selected with care to accurately determine ancestral states with confidence.}, } @article {pmid29617990, year = {2018}, author = {Wu, S and Ou, H and Liu, T and Wang, D and Zhao, J}, title = {Structure and dynamics of microbiomes associated with the marine sponge Tedania sp. during its life cycle.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy055}, pmid = {29617990}, issn = {1574-6941}, abstract = {Tedania sp. is a dominant sponge that is ubiquitous along the southeast coast of China. High-throughput sequencing and transmission electron microscopy were used to describe a detailed profile of sponge-associated microbiomes at seven life stages: adult, embryo-containing spawning adult, embryo, pre-competent larva at 2 h and 4 h, competent larva at 8 h and post-larva within 1-2h after settlement, as well as the surrounding seawater. Among a total of 15098 operational taxonomic units (OTUs), 13 were present exclusively in all stages of the sponge life cycle and could thus be identified as sponge-specific bacteria. Many OTUs were shared between the sponge and seawater, though abundance differed. The relative abundance of β-Proteobacteria associated with sponges was much higher than found in seawater. The microbiomes from each life stage also exhibited a characteristic distribution. Synechococcales dominated in adults, and Enterobacteriaceae was prominent in larvae. The competent larva was notable, with sharp increases in the total OTUs, diversity indices, richness estimates and unique OTUs. Some bacterial groups that were rare in other sponge stages and seawater, such as Clostridia (5.6%), were markedly more abundant in competent larvae. In conclusion, this work greatly advances our understanding of the dynamics and persistence of the sponge-microbe association.}, } @article {pmid29617987, year = {2018}, author = {Nilsson, LKJ and Sharma, A and Bhatnagar, RK and Bertilsson, S and Terenius, O}, title = {Presence of Aedes and Anopheles mosquito larvae is correlated to bacteria found in domestic water-storage containers.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy058}, pmid = {29617987}, issn = {1574-6941}, abstract = {Water-storage containers are common in households where access to water is scarce and often act as breeding sites for vector mosquitoes. Bacteria in these containers may be important for attracting or repelling ovipositing mosquitoes. We hypothesized that bacterial community composition in water-storage containers would represent either inhibitory or suitable environmental conditions for mosquito larvae. To investigate this, we characterized the bacterial community composition in water-storage containers and correlated these communities to Aedes and Anopheles larval densities. Water samples were collected over two years from 13 containers in an Indian village and analyzed by high throughput 16S rRNA gene amplicon sequencing. Comparisons of bacterial community composition between water with and without mosquito larvae showed that Xanthomonadaceae, Comamonadaceae and Burkholderiaceae were more common (P < 0.05) in absence of larvae, while Lachnospiraceae, Synechococcaceae, Alcaligenaceae and Cryomorphaceae were more common (P < 0.05) in presence of larvae. Indicator analysis identified operational taxonomic units designated as CL500-29 marine group (Acidimicrobiaceae) and FukuN101 (Microbacteriaceae) for absence and presence of larvae, respectively. These results contribute to the understanding of which bacteria, directly or indirectly, can be linked to absence or presence of mosquitoes around households and set the basis for potential measures to be taken against these vector mosquitoes.}, } @article {pmid29617984, year = {2018}, author = {Mateos-Rivera, A and Øvreås, L and Wilson, B and Yde, JC and Finster, KW}, title = {Activity and diversity of methane-oxidizing bacteria along a Norwegian sub-Arctic glacier forefield.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy059}, pmid = {29617984}, issn = {1574-6941}, abstract = {Methane (CH4) is one of the most abundant greenhouse gases in the atmosphere and identification of its sources and sinks is crucial for the reliability of climate model outputs. Although CH4 production and consumption rates have been reported from a broad spectrum of environments, data obtained from glacier forefields are restricted to a few locations. We report the activities of methanotrophic communities and their diversity along a chronosequence in front of a sub-Arctic glacier using high-throughput sequencing and gas flux measurements. CH4 oxidation rates were measured in the field throughout the growing season during three sampling times at eight different sampling points in combination with laboratory incubation experiments. The overall results showed that the methanotrophic community had similar trends of increased CH4 consumption and increased abundance as a function of soil development and time of year. Sequencing results revealed that the methanotrophic community was dominated by a few OTUs and that a short-term increase in CH4 concentration, as performed in the field measurements, altered slightly the relative abundance of the OTUs.}, } @article {pmid29617896, year = {2018}, author = {Hoeppner, MP and Denisenko, E and Gardner, PP and Schmeier, S and Poole, AM}, title = {An Evaluation of Function of Multicopy Noncoding RNAs in Mammals Using ENCODE/FANTOM Data and Comparative Genomics.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1451-1462}, pmid = {29617896}, issn = {1537-1719}, abstract = {Mammalian diversification has coincided with a rapid proliferation of various types of noncoding RNAs, including members of both snRNAs and snoRNAs. The significance of this expansion however remains obscure. While some ncRNA copy-number expansions have been linked to functionally tractable effects, such events may equally likely be neutral, perhaps as a result of random retrotransposition. Hindering progress in our understanding of such observations is the difficulty in establishing function for the diverse features that have been identified in our own genome. Projects such as ENCODE and FANTOM have revealed a hidden world of genomic expression patterns, as well as a host of other potential indicators of biological function. However, such projects have been criticized, particularly from practitioners in the field of molecular evolution, where many suspect these data provide limited insight into biological function. The molecular evolution community has largely taken a skeptical view, thus it is important to establish tests of function. We use a range of data, including data drawn from ENCODE and FANTOM, to examine the case for function for the recent copy number expansion in mammals of six evolutionarily ancient RNA families involved in splicing and rRNA maturation. We use several criteria to assess evidence for function: conservation of sequence and structure, genomic synteny, evidence for transposition, and evidence for species-specific expression. Applying these criteria, we find that only a minority of loci show strong evidence for function and that, for the majority, we cannot reject the null hypothesis of no function.}, } @article {pmid29617834, year = {2018}, author = {Hayward, JA and Tachedjian, M and Cui, J and Cheng, AZ and Johnson, A and Baker, ML and Harris, RS and Wang, LF and Tachedjian, G}, title = {Differential Evolution of Antiretroviral Restriction Factors in Pteropid Bats as Revealed by APOBEC3 Gene Complexity.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1626-1637}, pmid = {29617834}, issn = {1537-1719}, support = {F30 CA200432/CA/NCI NIH HHS/United States ; R37 AI064046/AI/NIAID NIH HHS/United States ; }, abstract = {Bats have attracted attention in recent years as important reservoirs of viruses deadly to humans and other mammals. These infections are typically nonpathogenic in bats raising questions about innate immune differences that might exist between bats and other mammals. The APOBEC3 gene family encodes antiviral DNA cytosine deaminases with important roles in the suppression of diverse viruses and genomic parasites. Here, we characterize pteropid APOBEC3 genes and show that species within the genus Pteropus possess the largest and most diverse array of APOBEC3 genes identified in any mammal reported to date. Several bat APOBEC3 proteins are antiviral as demonstrated by restriction of retroviral infectivity using HIV-1 as a model, and recombinant A3Z1 subtypes possess strong DNA deaminase activity. These genes represent the first group of antiviral restriction factors identified in bats with extensive diversification relative to homologues in other mammals.}, } @article {pmid29617830, year = {2018}, author = {Librado, P and Orlando, L}, title = {Detecting Signatures of Positive Selection along Defined Branches of a Population Tree Using LSD.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1520-1535}, pmid = {29617830}, issn = {1537-1719}, abstract = {Identifying the genomic basis underlying local adaptation is paramount to evolutionary biology, and bears many applications in the fields of conservation biology, crop, and animal breeding, as well as personalized medicine. Although many approaches have been developed to detect signatures of positive selection within single populations and population pairs, the increasing wealth of high-throughput sequencing data requires improved methods capable of handling multiple, and ideally large number of, populations in a single analysis. In this study, we introduce LSD (levels of exclusively shared differences), a fast and flexible framework to perform genome-wide selection scans, along the internal and external branches of a given population tree. We use forward simulations to demonstrate that LSD can identify branches targeted by positive selection with remarkable sensitivity and specificity. We illustrate a range of potential applications by analyzing data from the 1000 Genomes Project and uncover a list of adaptive candidates accompanying the expansion of anatomically modern humans out of Africa and their spread to Europe.}, } @article {pmid29617828, year = {2018}, author = {Meier, JI and Marques, DA and Wagner, CE and Excoffier, L and Seehausen, O}, title = {Genomics of Parallel Ecological Speciation in Lake Victoria Cichlids.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1489-1506}, doi = {10.1093/molbev/msy051}, pmid = {29617828}, issn = {1537-1719}, abstract = {The genetic basis of parallel evolution of similar species is of great interest in evolutionary biology. In the adaptive radiation of Lake Victoria cichlid fishes, sister species with either blue or red-back male nuptial coloration have evolved repeatedly, often associated with shallower and deeper water, respectively. One such case is blue and red-backed Pundamilia species, for which we recently showed that a young species pair may have evolved through "hybrid parallel speciation". Coalescent simulations suggested that the older species P. pundamilia (blue) and P. nyererei (red-back) admixed in the Mwanza Gulf and that new "nyererei-like" and "pundamilia-like" species evolved from the admixed population. Here, we use genome scans to study the genomic architecture of differentiation, and assess the influence of hybridization on the evolution of the younger species pair. For each of the two species pairs, we find over 300 genomic regions, widespread across the genome, which are highly differentiated. A subset of the most strongly differentiated regions of the older pair are also differentiated in the younger pair. These shared differentiated regions often show parallel allele frequency differences, consistent with the hypothesis that admixture-derived alleles were targeted by divergent selection in the hybrid population. However, two-thirds of the genomic regions that are highly differentiated between the younger species are not highly differentiated between the older species, suggesting independent evolutionary responses to selection pressures. Our analyses reveal how divergent selection on admixture-derived genetic variation can facilitate new speciation events.}, } @article {pmid29617811, year = {2018}, author = {Hao, Y and Washburn, JD and Rosenthal, J and Nielsen, B and Lyons, E and Edger, PP and Pires, JC and Conant, GC}, title = {Patterns of Population Variation in Two Paleopolyploid Eudicot Lineages Suggest That Dosage-Based Selection on Homeologs Is Long-Lived.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {999-1011}, pmid = {29617811}, issn = {1759-6653}, mesh = {Arabidopsis/genetics ; Brassica/genetics ; *Evolution, Molecular ; Gene Dosage/genetics ; Gene Duplication ; Genes, Plant/genetics ; Genome, Plant/*genetics ; Phylogeny ; Polyploidy ; Selection, Genetic/*genetics ; }, abstract = {Genes that are inherently subject to strong selective constraints tend to be overretained in duplicate after polyploidy. They also continue to experience similar, but somewhat relaxed, constraints after that polyploidy event. We sought to assess for how long the influence of polyploidy is felt on these genes' selective pressures. We analyzed two nested polyploidy events in Brassicaceae: the At-α genome duplication that is the most recent polyploidy in the model plant Arabidopsis thaliana and a more recent hexaploidy shared by the genus Brassica and its relatives. By comparing the strength and direction of the natural selection acting at the population and at the species level, we find evidence for continued intensified purifying selection acting on retained duplicates from both polyploidies even down to the present. The constraint observed in preferentially retained genes is not a result of the polyploidy event: the orthologs of such genes experience even stronger constraint in nonpolyploid outgroup genomes. In both the Arabidopsis and Brassica lineages, we further find evidence for segregating mildly deleterious variants, confirming that the population-level data uncover patterns not visible with between-species comparisons. Using the A. thaliana metabolic network, we also explored whether network position was correlated with the measured selective constraint. At both the population and species level, nodes/genes tended to show similar constraints to their neighbors. Our results paint a picture of the long-lived effects of polyploidy on plant genomes, suggesting that even yesterday's polyploids still have distinct evolutionary trajectories.}, } @article {pmid29617810, year = {2018}, author = {Murillo, T and Ramírez-Vargas, G and Riedel, T and Overmann, J and Andersen, JM and Guzmán-Verri, C and Chaves-Olarte, E and Rodríguez, C}, title = {Two Groups of Cocirculating, Epidemic Clostridiodes difficile Strains Microdiversify through Different Mechanisms.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {982-998}, pmid = {29617810}, issn = {1759-6653}, mesh = {Clostridium Infections/*genetics/microbiology ; Clostridium difficile/*genetics ; Disease Outbreaks ; Drug Resistance, Bacterial/genetics ; Gene Transfer, Horizontal/*genetics ; *Genetic Variation ; Genome, Bacterial ; Genotype ; Humans ; Mutation ; Virulence/genetics ; }, abstract = {Clostridiodes difficile strains from the NAPCR1/ST54 and NAP1/ST01 types have caused outbreaks despite of their notable differences in genome diversity. By comparing whole genome sequences of 32 NAPCR1/ST54 isolates and 17 NAP1/ST01 recovered from patients infected with C. difficile we assessed whether mutation, homologous recombination (r) or nonhomologous recombination (NHR) through lateral gene transfer (LGT) have differentially shaped the microdiversification of these strains. The average number of single nucleotide polymorphisms (SNPs) in coding sequences (NAPCR1/ST54 = 24; NAP1/ST01 = 19) and SNP densities (NAPCR1/ST54 = 0.54/kb; NAP1/ST01 = 0.46/kb) in the NAPCR1/ST54 and NAP1/ST01 isolates was comparable. However, the NAP1/ST01 isolates showed 3× higher average dN/dS rates (8.35) that the NAPCR1/ST54 isolates (2.62). Regarding r, whereas 31 of the NAPCR1/ST54 isolates showed 1 recombination block (3,301-8,226 bp), the NAP1/ST01 isolates showed no bases in recombination. As to NHR, the pangenome of the NAPCR1/ST54 isolates was larger (4,802 gene clusters, 26% noncore genes) and more heterogeneous (644 ± 33 gene content changes) than that of the NAP1/ST01 isolates (3,829 gene clusters, ca. 6% noncore genes, 129 ± 37 gene content changes). Nearly 55% of the gene content changes seen among the NAPCR1/ST54 isolates (355 ± 31) were traced back to MGEs with putative genes for antimicrobial resistance and virulence factors that were only detected in single isolates or isolate clusters. Congruently, the LGT/SNP rate calculated for the NAPCR1/ST54 isolates (26.8 ± 2.8) was 4× higher than the one obtained for the NAP1/ST1 isolates (6.8 ± 2.0). We conclude that NHR-LGT has had a greater role in the microdiversification of the NAPCR1/ST54 strains, opposite to the NAP1/ST01 strains, where mutation is known to play a more prominent role.}, } @article {pmid29617801, year = {2018}, author = {Suárez-Villagrán, MY and Azevedo, RBR and Miller, JH}, title = {Influence of Electron-Holes on DNA Sequence-Specific Mutation Rates.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1039-1047}, pmid = {29617801}, issn = {1759-6653}, support = {R01 GM101352/GM/NIGMS NIH HHS/United States ; }, mesh = {Base Sequence/genetics ; CpG Islands/genetics ; DNA Replication/*genetics ; DNA, Mitochondrial/*genetics ; Electrons ; *Evolution, Molecular ; Genome, Human/*genetics ; Humans ; Mutagenesis ; Mutation Rate ; }, abstract = {Biases in mutation rate can influence molecular evolution, yielding rates of evolution that vary widely in different parts of the genome and even among neighboring nucleotides. Here, we explore one possible mechanism of influence on sequence-specific mutation rates, the electron-hole, which can localize and potentially trigger a replication mismatch. A hole is a mobile site of positive charge created during one-electron oxidation by, for example, radiation, contact with a mutagenic agent, or oxidative stress. Its quantum wavelike properties cause it to localize at various sites with probabilities that vary widely, by orders of magnitude, and depend strongly on the local sequence. We find significant correlations between hole probabilities and mutation rates within base triplets, observed in published mutation accumulation experiments on four species of bacteria. We have also computed hole probability spectra for hypervariable segment I of the human mtDNA control region, which contains several mutational hotspots, and for heptanucleotides in noncoding regions of the human genome, whose polymorphism levels have recently been reported. We observe significant correlations between hole probabilities, and context-specific mutation and substitution rates. The correlation with hole probability cannot be explained entirely by CpG methylation in the heptanucleotide data. Peaks in hole probability tend to coincide with mutational hotspots, even in mtDNA where CpG methylation is rare. Our results suggest that hole-enhanced mutational mechanisms, such as oxidation-stabilized tautomerization and base deamination, contribute to molecular evolution.}, } @article {pmid29617800, year = {2018}, author = {Klinger, CM and Paoli, L and Newby, RJ and Wang, MY and Carroll, HD and Leblond, JD and Howe, CJ and Dacks, JB and Bowler, C and Cahoon, AB and Dorrell, RG and Richardson, E}, title = {Plastid Transcript Editing across Dinoflagellate Lineages Shows Lineage-Specific Application but Conserved Trends.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1019-1038}, pmid = {29617800}, issn = {1759-6653}, support = {R21 ES021028/ES/NIEHS NIH HHS/United States ; }, mesh = {Conserved Sequence/*genetics ; Dinoflagellida/*genetics ; *Evolution, Molecular ; Genome ; Phylogeny ; Plastids/*genetics ; RNA Editing/genetics ; Symbiosis/genetics ; }, abstract = {Dinoflagellates are a group of unicellular protists with immense ecological and evolutionary significance and cell biological diversity. Of the photosynthetic dinoflagellates, the majority possess a plastid containing the pigment peridinin, whereas some lineages have replaced this plastid by serial endosymbiosis with plastids of distinct evolutionary affiliations, including a fucoxanthin pigment-containing plastid of haptophyte origin. Previous studies have described the presence of widespread substitutional RNA editing in peridinin and fucoxanthin plastid genes. Because reports of this process have been limited to manual assessment of individual lineages, global trends concerning this RNA editing and its effect on the biological function of the plastid are largely unknown. Using novel bioinformatic methods, we examine the dynamics and evolution of RNA editing over a large multispecies data set of dinoflagellates, including novel sequence data from the peridinin dinoflagellate Pyrocystis lunula and the fucoxanthin dinoflagellate Karenia mikimotoi. We demonstrate that while most individual RNA editing events in dinoflagellate plastids are restricted to single species, global patterns, and functional consequences of editing are broadly conserved. We find that editing is biased toward specific codon positions and regions of genes, and generally corrects otherwise deleterious changes in the genome prior to translation, though this effect is more prevalent in peridinin than fucoxanthin lineages. Our results support a model for promiscuous editing application subsequently shaped by purifying selection, and suggest the presence of an underlying editing mechanism transferred from the peridinin-containing ancestor into fucoxanthin plastids postendosymbiosis, with remarkably conserved functional consequences in the new lineage.}, } @article {pmid29617761, year = {2018}, author = {Abrahams, L and Hurst, LD}, title = {Refining the Ambush Hypothesis: Evidence That GC- and AT-Rich Bacteria Employ Different Frameshift Defence Strategies.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1153-1173}, pmid = {29617761}, issn = {1759-6653}, support = {669207//European Research Council/International ; MR/L007215/1//Medical Research Council/United Kingdom ; }, mesh = {Bacteria/*genetics ; Base Composition/genetics ; Codon, Terminator/genetics ; *Evolution, Molecular ; Frameshift Mutation/*genetics ; GC Rich Sequence/*genetics ; Genome, Bacterial/genetics ; Reading Frames/genetics ; }, abstract = {Stop codons are frequently selected for beyond their regular termination function for error control. The "ambush hypothesis" proposes out-of-frame stop codons (OSCs) terminating frameshifted translations are selected for. Although early indirect evidence was partially supportive, recent evidence suggests OSC frequencies are not exceptional when considering underlying nucleotide content. However, prior null tests fail to control amino acid/codon usages or possible local mutational biases. We therefore return to the issue using bacterial genomes, considering several tests defining and testing against a null. We employ simulation approaches preserving amino acid order but shuffling synonymous codons or preserving codons while shuffling amino acid order. Additionally, we compare codon usage in amino acid pairs, where one codon can but the next, otherwise identical codon, cannot encode an OSC. OSC frequencies exceed expectations typically in AT-rich genomes, the +1 frame and for TGA/TAA but not TAG. With this complex evidence, simply rejecting or accepting the ambush hypothesis is not warranted. We propose a refined post hoc model, whereby AT-rich genomes have more accidental frameshifts, handled by RF2-RF3 complexes (associated with TGA/TAA) and are mostly +1 (or -2) slips. Supporting this, excesses positively correlate with in silico predicted frameshift probabilities. Thus, we propose a more viable framework, whereby genomes broadly adopt one of the two strategies to combat frameshifts: preventing frameshifting (GC-rich) or permitting frameshifts but minimizing impacts when most are caught early (AT-rich). Our refined framework holds promise yet some features, such as the bias of out-of-frame sense codons, remain unexplained.}, } @article {pmid29616894, year = {2018}, author = {Singh, H and Kaur, M and Sharma, S and Kaur, L and Mishra, S and Tanuku, NRS and Pinnaka, AK}, title = {Bacillus alkalilacus sp. nov., isolated from a sediment sample from a lake in India.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1665-1671}, doi = {10.1099/ijsem.0.002726}, pmid = {29616894}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; India ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An aerobic, endospore-forming, haloalkali-tolerant, Gram-stain-positive, motile, rod-shaped bacterium, designated strain AK73T, was isolated from a sediment sample collected from Sambhar lake, Jaipur, Rajasthan, India. Colonies were circular, 1-2 mm in diameter, glossy, smooth, yellowish and convex with an entire margin after 48 h growth on marine agar at pH 9 and 37 °C. Growth occurred at 15-42 °C, 0-10 % (w/v) NaCl and at a pH range of 7-12. Strain AK73T was positive for catalase and arginine dihydrolase 2 activities, hydrolysis of Tweens 20, 40 and 80, and negative for esculinase, caseinase, gelatinase, β-galactosidase, lipase (Tween 60) and urease activities. The fatty acids were dominated by branched iso-, anteiso-, saturated fatty acids with a high abundance of iso-C15 : 0, anteiso-C15 : 0, C16 : 0 and anteiso-C17 : 0; MK-7 was the major menaquinone. The cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminophospholipid, four unidentified phospholipids and three unidentified lipids. The DNA G+C content of strain AK73T was 54 mol%. Analysis based on comparative 16S rRNA gene sequence analysis indicated that Bacillus alcalophilus was the nearest phylogenetic neighbour, with a pair-wise sequence similarity of 96.0 %. Phylogenetic analysis showed that strain AK73T formed a separate lineage but was loosely associated with a peripheral cluster of organisms that contained Bacillus gibsonii, Bacillus murimartini and Bacillus plakortidis with similarity values of 93.6, 93.5 and 93.4 %, respectively. Based on its phenotypic characteristics and on phylogenetic inference, strain AK73T represents a novel species of the genus Bacillus, for which the name Bacillus alkalilacus sp. nov. is proposed. The type strain is AK73T (=JCM 32184T=MTCC 12637T=KCTC 33880T).}, } @article {pmid29616893, year = {2018}, author = {Pal, D and Kaur, N and Sudan, SK and Bisht, B and Krishnamurthi, S and Mayilraj, S}, title = {Acidovorax kalamii sp. nov., isolated from a water sample of the river Ganges.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1719-1724}, doi = {10.1099/ijsem.0.002736}, pmid = {29616893}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Comamonadaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; India ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-negative, rod-shaped, aerobic, straw yellow, motile strain, designated KNDSW-TSA6T, belonging to the genus Acidovorax, was isolated from a water sample of the river Ganges, downstream of the city of Kanpur, Uttar Pradesh, India. Cells were aerobic, non-endospore-forming and motile with single polar flagella. It differed from its phylogenetically related strains by phenotypic characteristics such as hydrolysis of urea, gelatin, casein and DNA, and the catalase reaction. The major fatty acids were C16 : 1ω7c/C16 : 1ω6c, C16 : 0 and C18 : 1ω7c/C18 : 1ω6c. Phylogenetic analysis based on 16S rRNA and housekeeping genes (gyrb, recA and rpoB gene sequences), confirmed its placement within the genus Acidovorax as a novel species. Strain KNDSW-TSA6T showed highest 16S rRNA sequence similarity to Acidovorax soli BL21T (98.9 %), Acidovorax delafieldii ATCC 17505T (98.8 %), Acidovorax temperans CCUG 11779T (98.2 %), Acidovorax caeni R-24608T (97.9 %) and Acidovorax radicis N35T (97.6 %). The digital DNA-DNA hybridization and average nucleotide identity values calculated from whole genome sequences between strain KNDSW-TSA6T and the two most closely related strains A. soli BL21T and A. delafieldii ATCC 17505T were below the threshold values of 70 and 95 % respectively. Thus, the data from the polyphasic taxonomic analysis clearly indicates that strain KNDSW-TSA6T represents a novel species, for which the name Acidovorax kalamii sp. nov. is proposed. The type strain is Acidovorax kalamii (=MTCC 12652T=KCTC 52819T=VTCC-B-910010T).}, } @article {pmid29616891, year = {2018}, author = {Zhu, S and Lin, D and Xiong, S and Wang, X and Xue, Z and Dong, B and Shen, X and Ma, X and Chen, J and Yang, J}, title = {Carnobacterium antarcticum sp. nov., a psychrotolerant, alkaliphilic bacterium isolated from sandy soil in Antarctica.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1672-1677}, doi = {10.1099/ijsem.0.002727}, pmid = {29616891}, issn = {1466-5034}, mesh = {Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; Carnobacterium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A novel, alkaliphilic, psychrotolerant, facultative anaerobe, designated CP1T, was isolated from sandy soil near the Davis Station in Antarctica. The short-rod-shaped cells displayed Gram-positive staining and did not form spores. Strain CP1T was able to grow at temperatures between 4 and 36 °C, pH 6.0-9.5, and in the presence of up to 5.0 % (w/v) NaCl. 16S rRNA gene and multilocus (pheS, rpoA, and atpA) sequence analysis revealed Carnobacterium mobile DSM 4848T and Carnobacterium iners LMG 26642T as the closest relatives (97.4 and 97.1 % 16S rRNA gene sequence similarity, respectively). The genomic G+C content was 38.1 mol%, and DNA-DNA hybridization with DSM 4848T revealed 32.4±3.4 % similarity. The major fatty acid components were C14 : 0 and C16 : 1ω9c. The cell wall contained meso-diaminopimelic acid and was of peptidoglycan type A1γ. Based on physiological, genotypic and biochemical characteristics, strain CP1T represents a novel species of the genus Carnobacterium for which the name Carnobacterium antarcticum sp. nov. is proposed. The type strain is CP1T (=DSM 103363T=CGMCC 1.15643T).}, } @article {pmid29615821, year = {2018}, author = {York, A}, title = {Environmental microbiology: Marine biogeochemical cycles in a changing world.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {259}, pmid = {29615821}, issn = {1740-1534}, } @article {pmid29615820, year = {2018}, author = {Otto, G}, title = {Human evolution: Archaic admixture with Denisovans.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {251}, pmid = {29615820}, issn = {1471-0064}, } @article {pmid29615789, year = {2018}, author = {Dasgupta, S and Rajapakshe, K and Zhu, B and Nikolai, BC and Yi, P and Putluri, N and Choi, JM and Jung, SY and Coarfa, C and Westbrook, TF and Zhang, XH and Foulds, CE and Tsai, SY and Tsai, MJ and O'Malley, BW}, title = {Metabolic enzyme PFKFB4 activates transcriptional coactivator SRC-3 to drive breast cancer.}, journal = {Nature}, volume = {556}, number = {7700}, pages = {249-254}, pmid = {29615789}, issn = {1476-4687}, support = {P30 CA016056/CA/NCI NIH HHS/United States ; R01 CA220297/CA/NCI NIH HHS/United States ; P01 DK059820/DK/NIDDK NIH HHS/United States ; R01 HD007857/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; K22 CA207578/CA/NCI NIH HHS/United States ; P50 CA186784/CA/NCI NIH HHS/United States ; HD08818/NH/NIH HHS/United States ; }, mesh = {Activating Transcription Factor 4/metabolism ; Animals ; Breast Neoplasms/enzymology/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Female ; *Gene Expression Regulation, Neoplastic ; Glucose/*metabolism ; Glycolysis ; Humans ; Lung Neoplasms/prevention & control/secondary ; Mice ; Neoplasm Metastasis ; Nuclear Receptor Coactivator 3/*metabolism ; Pentose Phosphate Pathway ; Phosphofructokinase-2/*metabolism ; Phosphorylation ; Phosphoserine/metabolism ; Prognosis ; Purines/biosynthesis/metabolism ; RNA Interference ; Receptors, Estrogen/metabolism ; *Transcriptional Activation ; Transketolase/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Alterations in both cell metabolism and transcriptional programs are hallmarks of cancer that sustain rapid proliferation and metastasis 1 . However, the mechanisms that control the interaction between metabolic reprogramming and transcriptional regulation remain unclear. Here we show that the metabolic enzyme 6-phosphofructo-2-kinase/fructose-2,6-bisphosphatase 4 (PFKFB4) regulates transcriptional reprogramming by activating the oncogenic steroid receptor coactivator-3 (SRC-3). We used a kinome-wide RNA interference-based screening method to identify potential kinases that modulate the intrinsic SRC-3 transcriptional response. PFKFB4, a regulatory enzyme that synthesizes a potent stimulator of glycolysis 2 , is found to be a robust stimulator of SRC-3 that coregulates oestrogen receptor. PFKFB4 phosphorylates SRC-3 at serine 857 and enhances its transcriptional activity, whereas either suppression of PFKFB4 or ectopic expression of a phosphorylation-deficient Ser857Ala mutant SRC-3 abolishes the SRC-3-mediated transcriptional output. Functionally, PFKFB4-driven SRC-3 activation drives glucose flux towards the pentose phosphate pathway and enables purine synthesis by transcriptionally upregulating the expression of the enzyme transketolase. In addition, the two enzymes adenosine monophosphate deaminase-1 (AMPD1) and xanthine dehydrogenase (XDH), which are involved in purine metabolism, were identified as SRC-3 targets that may or may not be directly involved in purine synthesis. Mechanistically, phosphorylation of SRC-3 at Ser857 increases its interaction with the transcription factor ATF4 by stabilizing the recruitment of SRC-3 and ATF4 to target gene promoters. Ablation of SRC-3 or PFKFB4 suppresses breast tumour growth in mice and prevents metastasis to the lung from an orthotopic setting, as does Ser857Ala-mutant SRC-3. PFKFB4 and phosphorylated SRC-3 levels are increased and correlate in oestrogen receptor-positive tumours, whereas, in patients with the basal subtype, PFKFB4 and SRC-3 drive a common protein signature that correlates with the poor survival of patients with breast cancer. These findings suggest that the Warburg pathway enzyme PFKFB4 acts as a molecular fulcrum that couples sugar metabolism to transcriptional activation by stimulating SRC-3 to promote aggressive metastatic tumours.}, } @article {pmid29615533, year = {2018}, author = {Shen, H}, title = {Core Concept: Organoids have opened avenues into investigating numerous diseases. But how well do they mimic the real thing?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3507-3509}, pmid = {29615533}, issn = {1091-6490}, mesh = {*Biomimetics ; Cystic Fibrosis/*physiopathology ; Humans ; *Models, Biological ; *Organogenesis ; Organoids/*cytology/*physiology ; Stem Cells/*cytology ; }, } @article {pmid29615532, year = {2018}, author = {Beans, C}, title = {Science and Culture: Wearable tech meets tattoo art in a bid to revolutionize both.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3504-3506}, pmid = {29615532}, issn = {1091-6490}, mesh = {Biosensing Techniques/*instrumentation ; *Culture ; Humans ; *Science ; Sweat/chemistry/*metabolism ; Tattooing/*methods ; Wearable Electronic Devices/*standards ; Wireless Technology/*instrumentation ; }, } @article {pmid29615514, year = {2018}, author = {Orozco, CA and Martinez-Bosch, N and Guerrero, PE and Vinaixa, J and Dalotto-Moreno, T and Iglesias, M and Moreno, M and Djurec, M and Poirier, F and Gabius, HJ and Fernandez-Zapico, ME and Hwang, RF and Guerra, C and Rabinovich, GA and Navarro, P}, title = {Targeting galectin-1 inhibits pancreatic cancer progression by modulating tumor-stroma crosstalk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3769-E3778}, pmid = {29615514}, issn = {1091-6490}, support = {P30 DK084567/DK/NIDDK NIH HHS/United States ; P50 CA102701/CA/NCI NIH HHS/United States ; R01 CA136526/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Pancreatic Ductal/blood supply/genetics/immunology/*therapy ; Cell Division/genetics ; Cell Movement/genetics ; Culture Media, Conditioned ; Galectin 1/*physiology ; Galectins/genetics/*physiology ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; Gene Ontology ; Heterografts ; Humans ; Lymphocytes, Tumor-Infiltrating/immunology ; Mice ; Mice, Knockout ; Mice, Transgenic ; *Molecular Targeted Therapy ; Neoplasm Metastasis ; Neovascularization, Pathologic ; Pancreatic Neoplasms/blood supply/genetics/immunology/*therapy ; Pancreatic Stellate Cells/metabolism/transplantation ; Paracrine Communication ; RNA, Small Interfering/genetics ; Stromal Cells/metabolism ; Tumor Microenvironment ; }, abstract = {Pancreatic ductal adenocarcinoma (PDA) remains one of the most lethal tumor types, with extremely low survival rates due to late diagnosis and resistance to standard therapies. A more comprehensive understanding of the complexity of PDA pathobiology, and especially of the role of the tumor microenvironment in disease progression, should pave the way for therapies to improve patient response rates. In this study, we identify galectin-1 (Gal1), a glycan-binding protein that is highly overexpressed in PDA stroma, as a major driver of pancreatic cancer progression. Genetic deletion of Gal1 in a Kras-driven mouse model of PDA (Ela-KrasG12Vp53-/-) results in a significant increase in survival through mechanisms involving decreased stroma activation, attenuated vascularization, and enhanced T cell infiltration leading to diminished metastasis rates. In a human setting, human pancreatic stellate cells (HPSCs) promote cancer proliferation, migration, and invasion via Gal1-driven pathways. Moreover, in vivo orthotopic coinjection of pancreatic tumor cells with Gal1-depleted HPSCs leads to impaired tumor formation and metastasis in mice. Gene-expression analyses of pancreatic tumor cells exposed to Gal1 reveal modulation of multiple regulatory pathways involved in tumor progression. Thus, Gal1 hierarchically regulates different events implicated in PDA biology including tumor cell proliferation, invasion, angiogenesis, inflammation, and metastasis, highlighting the broad therapeutic potential of Gal1-specific inhibitors, either alone or in combination with other therapeutic modalities.}, } @article {pmid29615513, year = {2018}, author = {Garg, N and Schiebinger, L and Jurafsky, D and Zou, J}, title = {Word embeddings quantify 100 years of gender and ethnic stereotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3635-E3644}, pmid = {29615513}, issn = {1091-6490}, mesh = {Culture ; Ethnic Groups ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Internet ; Language/*history ; *Machine Learning ; Male ; Minority Groups ; Newspapers as Topic ; Occupations ; Racism/*history ; Religion ; Sexism/*history ; Social Change ; *Stereotyping ; United States ; }, abstract = {Word embeddings are a powerful machine-learning framework that represents each English word by a vector. The geometric relationship between these vectors captures meaningful semantic relationships between the corresponding words. In this paper, we develop a framework to demonstrate how the temporal dynamics of the embedding helps to quantify changes in stereotypes and attitudes toward women and ethnic minorities in the 20th and 21st centuries in the United States. We integrate word embeddings trained on 100 y of text data with the US Census to show that changes in the embedding track closely with demographic and occupation shifts over time. The embedding captures societal shifts-e.g., the women's movement in the 1960s and Asian immigration into the United States-and also illuminates how specific adjectives and occupations became more closely associated with certain populations over time. Our framework for temporal analysis of word embedding opens up a fruitful intersection between machine learning and quantitative social science.}, } @article {pmid29615512, year = {2018}, author = {Carella, P and Gogleva, A and Tomaselli, M and Alfs, C and Schornack, S}, title = {Phytophthora palmivora establishes tissue-specific intracellular infection structures in the earliest divergent land plant lineage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3846-E3855}, pmid = {29615512}, issn = {1091-6490}, support = {BB/L014130/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Hyphae/pathogenicity/ultrastructure ; Marchantia/*microbiology/ultrastructure ; Phytophthora/*pathogenicity/ultrastructure ; Plant Diseases/*microbiology ; Symbiosis ; }, abstract = {The expansion of plants onto land was a formative event that brought forth profound changes to the earth's geochemistry and biota. Filamentous eukaryotic microbes developed the ability to colonize plant tissues early during the evolution of land plants, as demonstrated by intimate, symbiosis-like associations in >400 million-year-old fossils. However, the degree to which filamentous microbes establish pathogenic interactions with early divergent land plants is unclear. Here, we demonstrate that the broad host-range oomycete pathogen Phytophthora palmivora colonizes liverworts, the earliest divergent land plant lineage. We show that P. palmivora establishes a complex tissue-specific interaction with Marchantia polymorpha, where it completes a full infection cycle within air chambers of the dorsal photosynthetic layer. Remarkably, P. palmivora invaginates M. polymorpha cells with haustoria-like structures that accumulate host cellular trafficking machinery and the membrane syntaxin MpSYP13B, but not the related MpSYP13A. Our results indicate that the intracellular accommodation of filamentous microbes is an ancient plant trait that is successfully exploited by pathogens like P. palmivora.}, } @article {pmid29615511, year = {2018}, author = {Chien, YH}, title = {Does selecting ligand shape γδ-TCR repertoire?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3606}, pmid = {29615511}, issn = {1091-6490}, mesh = {*Ligands ; *Receptors, Antigen, T-Cell, gamma-delta ; }, } @article {pmid29615510, year = {2018}, author = {Fahl, SP and Wiest, DL}, title = {Reply to Chien: Clarification of the effect of ligand on γδ-TCR repertoire selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3607-E3608}, pmid = {29615510}, issn = {1091-6490}, mesh = {*Ligands ; *Receptors, Antigen, T-Cell, gamma-delta ; }, } @article {pmid29615135, year = {2018}, author = {Tolvanen, E and Koskela, TH and Mattila, KJ and Kosunen, E}, title = {Analysis of factors associated with waiting times for GP appointments in Finnish health centres: a QUALICOPC study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {220}, pmid = {29615135}, issn = {1756-0500}, support = {242141//Seventh Framework Programme/ ; 9N030//Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital/ ; 9R024//Competitive State Research Financing of the Expert Responsibility Area of Tampere University Hospital/ ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; *Appointments and Schedules ; Female ; Finland ; General Practitioners/*statistics & numerical data ; Health Services Accessibility/*statistics & numerical data ; Health Services Research ; Humans ; Male ; Middle Aged ; Primary Health Care/*statistics & numerical data ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: Access to care is a multidimensional concept, considered as a structural aspect of health care quality; it reflects the functioning of a health care organization. The aim of this study was to investigate patients' experiences of access to care and to analyse factors associated with waiting times to GP appointments at Finnish health centres. A questionnaire survey was addressed to Finnish GPs within the Quality and Costs of Primary Care in Europe study framework. Two to nine patients per GP completed the questionnaire, altogether 1196. Main outcome measures were waiting times for appointments with GPs and factors associated with waiting times. In addition, patients' opinions of access to appointments were analysed.

RESULTS: Of the 988 patients who had made their appointment in advance, 84.9% considered it easy to secure an appointment, with 51.9% obtaining an appointment within 1 week. Age and reason for contact were the most significant factors affecting the waiting time. Elderly patients tended to have longer waiting times than younger ones, even when reporting illness as their reason for contact. Thus, waiting times for appointments tend to be prolonged in particular for the elderly and there is room for improvement in the future.}, } @article {pmid29615129, year = {2018}, author = {Gitau, W and Masika, M and Musyoki, M and Museve, B and Mutwiri, T}, title = {Antimicrobial susceptibility pattern of Staphylococcus aureus isolates from clinical specimens at Kenyatta National Hospital.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {226}, pmid = {29615129}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*pharmacology ; Cross Infection/*epidemiology ; Drug Resistance, Bacterial/*drug effects ; Hospitals/*statistics & numerical data ; Humans ; Kenya/epidemiology ; Methicillin-Resistant Staphylococcus aureus/drug effects/isolation & purification ; Microbial Sensitivity Tests ; Retrospective Studies ; Staphylococcal Infections/*epidemiology ; Staphylococcus aureus/*drug effects/*isolation & purification ; }, abstract = {OBJECTIVE: To determine antibiotic susceptibility pattern of S. aureus isolates from clinical specimens collected from patients at Kenyatta National Hospital from March 2014-February 2016, and to determine the prevalence and quarterly trends of MRSA throughout the study period.

RESULTS: A total of 944 S. aureus isolates were analyzed. High sensitivity of S. aureus was observed for quinupristin/dalfopristin (100%), tigecycline (98.2), imipenem (98%), nitrofurantoin (97.6%), linezolid (97.3%), teicoplanin (97.1%) and vancomycin (95.1%). High resistance was recorded against penicillin G (91.9%), trimethoprim/sulfamethoxazole (56.9%) and tetracycline (33.2%). MRSA prevalence among the patients at KNH was 27.8%. Highest proportion (80%) of MRSA was in burns unit. Both MRSA and MSSA were highly susceptible to quinupristin/dalfopristin, tigecycline, linezolid, nitrofurantoin, ampicillin/sulbactam and vancomycin and showed high resistance to commonly used antibiotics such as gentamycin, erythromycin, levofloxacin and tetracycline. A majority of isolates were from pus specimen (68%).}, } @article {pmid29615120, year = {2018}, author = {W/Gebriel, TK and Dadi, TL and Mihrete, KM}, title = {Determinants of unjustified cesarean section in two hospitals southwestern Ethiopia: retrospective record review.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {219}, pmid = {29615120}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cesarean Section/*statistics & numerical data ; Ethiopia ; Female ; Hospitals/*statistics & numerical data ; Humans ; Obstetric Labor Complications/*surgery ; Pregnancy ; Prenatal Care/*statistics & numerical data ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: The study aimed to identify determinants of unjustified cesarean section in two hospitals southwestern Ethiopia using retrospective record review from January 2015 to January 2016.

RESULT: A total of 727 charts were included in the analysis. About 25% of the study participants had delivered by cesarean section in 1 year. Antenatal care visit (AOR = 0.003, 95% CI 0.00-0.07), labor abnormality (AOR = 10.1, 95% CI 4.61-22.1), and post term pregnancy (AOR = 10.6, 95% CI 4.85-23.1) were significantly associated with cesarean section when compared to their respective counterparts.}, } @article {pmid29615118, year = {2018}, author = {Pickett, T and David, AA}, title = {Global connectivity patterns of the notoriously invasive mussel, Mytilus galloprovincialis Lmk using archived CO1 sequence data.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {231}, pmid = {29615118}, issn = {1756-0500}, mesh = {*Animal Distribution ; Animals ; *Electron Transport Complex IV ; Genetics, Population ; Haplotypes ; *Introduced Species ; Mytilus/*classification/*genetics ; Spatial Analysis ; }, abstract = {OBJECTIVE: The invasive mussel, Mytilus galloprovincialis has established invasive populations across the globe and in some regions, have completely displaced native mussels through competitive exclusion. The objective of this study was to elucidate global connectivity patterns of M. galloprovincialis strictly using archived cytochrome c oxidase 1 sequence data obtained from public databases. Through exhaustive mining and the development of a systematic workflow, we compiled the most comprehensive global CO1 dataset for M. galloprovincialis thus far, consisting of 209 sequences representing 14 populations. Haplotype networks were constructed and genetic differentiation was assessed using pairwise analysis of molecular variance.

RESULTS: There was significant genetic structuring across populations with significant geographic patterning of haplotypes. In particular, South Korea, South China, Turkey and Australasia appear to be the most genetically isolated populations. However, we were unable to recover a northern and southern hemisphere grouping for M. galloprovincialis as was found in previous studies. These results suggest a complex dispersal pattern for M. galloprovincialis driven by several contributors including both natural and anthropogenic dispersal mechanisms along with the possibility of potential hybridization and ancient vicariance events.}, } @article {pmid29615117, year = {2018}, author = {Yadav, NS and Khadka, J and Grafi, G}, title = {Arabidopsis mutants may represent recombinant introgression lines.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {227}, pmid = {29615117}, issn = {1756-0500}, support = {175/12//Israel Science Foundation/ ; Post-doctoral fellowship//Jacob Blaustein Center for Scientific Cooperation/ ; Post-doctoral fellowship//PBC Program of Israeli Council for Higher Education/ ; }, mesh = {Arabidopsis/classification/*genetics ; Arabidopsis Proteins/*genetics ; *Ecotype ; }, abstract = {OBJECTIVES: It is a common practice in Arabidopsis to transfer a mutation generated in one genetic background to other genetic background via crossing. However, the drawback of this methodology is unavoidable presence of genomic fragments from the donor parent being often replacing desirable genomic fragments of the recurrent parent. Here, we highlighted problem of Arabidopsis mutants being recombinant introgression lines that can lead to unreliable and misinterpreted results.

RESULTS: We studied the regulation of low copy number transposable elements Tag1 and Evelknievel (EK), located at the end of the bottom arm of chromosome 1 and both are present in the Arabidopsis Landsberg erecta (Ler) but not in Columbia (Col) ecotype. Using various epigenetic mutants (cmt3, ddm1, kyp2, ago4, rdr2 hen1 etc.), we found that certain mutants in the Ler background are deficient of Tag1 or EK or both and represent recombinant introgression lines whereby chromosomal regions from Col have been recombined into the Ler genome. Our data support a recent proposal calling for formulating standards for authentication of plant lines that are used in plant research. Most important is to verify that a given trait or genomic locus under study is correctly identified, particularly when using mutants generated by crossing.}, } @article {pmid29615116, year = {2018}, author = {Velloso, FJ and Sogayar, MC and Correa, RG}, title = {Expression and in vitro assessment of tumorigenicity for NOD1 and NOD2 receptors in breast cancer cell lines.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {222}, pmid = {29615116}, issn = {1756-0500}, support = {P30 CA030199/CA/NCI NIH HHS/United States ; Science without Borders//CAPES/ ; }, mesh = {Breast Neoplasms ; Carcinogenicity Tests ; Cell Line, Tumor ; Female ; *Gene Expression Profiling ; Humans ; Nod1 Signaling Adaptor Protein/*metabolism ; Nod2 Signaling Adaptor Protein/*metabolism ; }, abstract = {OBJECTIVE: Immune-related pathways have been frequently associated to tumorigenesis. NOD1 and NOD2 are innate immune receptors responsible for sensing a subset of bacterial-derived components, and to further translate these pathogenic signals through pro-inflammatory and survival pathways. NOD1 and NOD2 have been further associated with tumorigenesis, particularly in gastrointestinal cancers. NOD1 has also been suggested to be a tumor suppressor gene in a model of estrogen receptor-dependent breast cancer. Contrarily, NOD2 polymorphisms are associated with higher risk of breast cancer, with no tumor suppressor role being reported. To better delineate this issue, we investigated NOD1 and NOD2 expression in a panel of breast cancer cell lines, as well as their potential impact in breast tumorigenesis based on in vitro assays.

RESULTS: The highly invasive Hs578T breast cell line presented the second highest NOD1 expression and the lowest NOD2 expression in our panel. Therefore, we investigated whether NOD1 and/or NOD2 might act as a tumor suppressor in this cell model. Our studies indicate that overexpression of either NOD1 or NOD2 reduces cell proliferation and increases clonogenic potential in vitro. Elucidation of NOD1 and NOD2 effects on tumor cell viability and proliferation may unveil potential targets for future therapeutic intervention.}, } @article {pmid29615115, year = {2018}, author = {Hayashi, M and Watanabe, A and Muramatsu, M and Yamashita, N}, title = {Effectiveness of personal genomic testing for disease-prevention behavior when combined with careful consultation with a physician: a preliminary study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {223}, pmid = {29615115}, issn = {1756-0500}, support = {JP26670363//JSPS KAKENHI/ ; }, mesh = {Adult ; *Direct-To-Consumer Screening and Testing ; Female ; *Genetic Counseling ; *Genetic Testing ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; Physicians ; *Primary Prevention ; *Risk Reduction Behavior ; }, abstract = {OBJECTIVES: There are many direct-to-consumer (DTC)-type personal genomic testing (PGT) services commercially available to the public, providing the specific disease susceptibilities of individuals. While these services do not appear to stimulate disease-prevention behavior, few studies have addressed the methods to do so. We investigated the effectiveness of combining a consultation with a physician with the delivery of test results from a DTC-type PGT, as a preliminary study to identify the effective genomic testing for disease-prevention. A prepared physician disclosed the PGT results of twenty healthy subjects and provided a specific consultation on the high-risk diseases for each subject. The effects on the sense of health, understanding of possible future diseases, and preventive behaviors for each subject were examined pre-PGT, post-PGT, and 3, 6, and 12 months post-PGT.

RESULTS: Significant increases between the pre- and post-PGT scores were observed for the awareness of lifestyle effects on developing those diseases (P < 0.05) and the awareness of the ability to influence disease onset (P < 0.01). The follow-up questionnaire results showed that over 60% of the subjects changed their lifestyles in favor of disease prevention. These results suggest that combining the DTC-PGT with a careful physician consultation may be effective at motivating people toward preventive behavior.}, } @article {pmid29615112, year = {2018}, author = {Jagnoor, J and Lukaszyk, C and Christou, A and Potokar, T and Chamania, S and Ivers, R}, title = {Where to from here? A quality improvement project investigating burns treatment and rehabilitation practices in India.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {224}, pmid = {29615112}, issn = {1756-0500}, support = {WCCPRD3608471 2015/572126//World Health Organization/International ; }, mesh = {Burns/rehabilitation/*therapy ; Community Health Services/*standards ; *Health Knowledge, Attitudes, Practice ; Hospitals/*standards ; Humans ; India ; Personnel, Hospital/*standards ; Process Assessment (Health Care)/*standards ; Quality Improvement/*standards ; }, abstract = {OBJECTIVE: To describe the capacity of the Indian healthcare system in providing appropriate and effective burns treatment and rehabilitation services.

RESULTS: Health professionals involved in burns treatment or rehabilitation at seven hospitals from four states in India were invited to participate in consultative meetings. Existing treatment and rehabilitation strategies, barriers and enablers to patient flow across the continuum of care and details on inpatient and outpatient rehabilitation were discussed during the meetings. Seventeen health professionals from various clinical backgrounds were involved in the consultation process. Key themes highlighted (a) a lack of awareness on burn first aid at the community level, (b) a lack of human resource to treat burn injuries in hospital settings, (c) a gap in burn care training for medical staff, (d) poor hospital infrastructure and (e) a variation in treatment practices and rehabilitation services available between hospitals. A number of opportunities exist to improve burns treatment and rehabilitation in India. Improvements would most effectively be achieved through promoting multidisciplinary care across a number of facilities and service providers. Further research is required to develop context-specific burn care models, determining how these can be integrated into the Indian healthcare system.}, } @article {pmid29615110, year = {2018}, author = {Zhou, X and Li, J and Guo, J and Geng, B and Ji, W and Zhao, Q and Li, J and Liu, X and Liu, J and Guo, Z and Cai, W and Ma, Y and Ren, D and Miao, J and Chen, S and Zhang, Z and Chen, J and Zhong, J and Liu, W and Zou, M and Li, Y and Cai, J}, title = {Gut-dependent microbial translocation induces inflammation and cardiovascular events after ST-elevation myocardial infarction.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {66}, pmid = {29615110}, issn = {2049-2618}, support = {81570335//National Natural Science Foundation of China/International ; 2014CB542302//National Basic Research Program of China/International ; R01 CA209886/CA/NCI NIH HHS/United States ; R01 CA196967/CA/NCI NIH HHS/United States ; CIFMS,2016-12M-1-006//CAMS Innovation Fund for Medical Sciences/International ; 81630014//National Natural Science Foundation of China/International ; 81500383//National Natural Science Foundation of China/International ; 81470541//National Natural Science Foundation of China/International ; }, mesh = {Aged ; Biodiversity ; Biomarkers ; Cardiovascular Diseases/*etiology/metabolism/physiopathology ; Case-Control Studies ; Female ; Follow-Up Studies ; *Gastrointestinal Microbiome ; Humans ; Inflammation/*etiology/metabolism/pathology ; Male ; Middle Aged ; Permeability ; ROC Curve ; ST Elevation Myocardial Infarction/*complications/metabolism/pathology ; Ventricular Function, Left ; }, abstract = {BACKGROUND: Post-infarction cardiovascular remodeling and heart failure are the leading cause of myocardial infarction (MI)-driven death during the past decades. Experimental observations have involved intestinal microbiota in the susceptibility to MI in mice; however, in humans, identifying whether translocation of gut bacteria to systemic circulation contributes to cardiovascular events post-MI remains a major challenge.

RESULTS: Here, we carried out a metagenomic analysis to characterize the systemic bacteria in a cohort of 49 healthy control individuals, 50 stable coronary heart disease (CHD) subjects, and 100 ST-segment elevation myocardial infarction (STEMI) patients. We report for the first time higher microbial richness and diversity in the systemic microbiome of STEMI patients. More than 12% of post-STEMI blood bacteria were dominated by intestinal microbiota (Lactobacillus, Bacteroides, and Streptococcus). The significantly increased product of gut bacterial translocation (LPS and D-lactate) was correlated with systemic inflammation and predicted adverse cardiovascular events. Following experimental MI, compromised left ventricle (LV) function and intestinal hypoperfusion drove gut permeability elevation through tight junction protein suppression and intestinal mucosal injury. Upon abrogation of gut bacterial translocation by antibiotic treatment, both systemic inflammation and cardiomyocyte injury in MI mice were alleviated.

CONCLUSIONS: Our results provide the first evidence that cardiovascular outcomes post-MI are driven by intestinal microbiota translocation into systemic circulation. New therapeutic strategies targeting to protect the gut barrier and eliminate gut bacteria translocation may reduce or even prevent cardiovascular events post-MI.}, } @article {pmid29615108, year = {2018}, author = {Cornuault, JK and Petit, MA and Mariadassou, M and Benevides, L and Moncaut, E and Langella, P and Sokol, H and De Paepe, M}, title = {Phages infecting Faecalibacterium prausnitzii belong to novel viral genera that help to decipher intestinal viromes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {65}, pmid = {29615108}, issn = {2049-2618}, mesh = {Animals ; Bacteriophages/*physiology/ultrastructure ; Biodiversity ; Colitis/etiology ; DNA Damage ; Dysbiosis ; Faecalibacterium prausnitzii/*virology ; *Gastrointestinal Microbiome ; Genome, Viral ; Humans ; Inflammatory Bowel Diseases/etiology ; Metagenome ; Metagenomics/methods ; Mice ; Retroelements ; Symbiosis ; }, abstract = {BACKGROUND: Viral metagenomic studies have suggested a role for bacteriophages in intestinal dysbiosis associated with several human diseases. However, interpretation of viral metagenomic studies is limited by the lack of knowledge of phages infecting major human gut commensal bacteria, such as Faecalibacterium prausnitzii, a bacterial symbiont repeatedly found depleted in inflammatory bowel disease (IBD) patients. In particular, no complete genomes of phages infecting F. prausnitzii are present in viral databases.

METHODS: We identified 18 prophages in 15 genomes of F. prausnitzii, used comparative genomics to define eight phage clades, and annotated the genome of the type phage of each clade. For two of the phages, we studied prophage induction in vitro and in vivo in mice. Finally, we aligned reads from already published viral metagenomic data onto the newly identified phages.

RESULTS: We show that each phage clade represents a novel viral genus and that a surprisingly large fraction of them (10 of the 18 phages) codes for a diversity-generating retroelement, which could contribute to their adaptation to the digestive tract environment. We obtained either experimental or in silico evidence of activity for at least one member of each genus. In addition, four of these phages are either significantly more prevalent or more abundant in stools of IBD patients than in those of healthy controls.

CONCLUSION: Since IBD patients generally have less F. prausnitzii in their microbiota than healthy controls, the higher prevalence or abundance of some of its phages may indicate that they are activated during disease. This in turn suggests that phages could trigger or aggravate F. prausnitzii depletion in patients. Our results show that prophage detection in sequenced strains of the microbiota can usefully complement viral metagenomic studies.}, } @article {pmid29615107, year = {2018}, author = {Surani, SR and Hesselbacher, S and Surani, Z and Mokhasi, M and Surani, SS and Guardiola, J and Quisenberry, L and Surani, SS}, title = {Development and validation of a tool to assess knowledge of healthy lifestyles in early grade school children.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {225}, pmid = {29615107}, issn = {1756-0500}, mesh = {Child ; Child, Preschool ; Female ; *Health Knowledge, Attitudes, Practice ; *Healthy Lifestyle ; Humans ; Male ; *Psychometrics/instrumentation/methods/standards ; Reproducibility of Results ; Schools ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Healthy habits during childhood has been of prime importance. We aimed to gather baseline information about health habits from children in kindergarten and first grade (typically ages 5-7). Our objectives were to validate the questionnaire in assessing health habits, as well as the electronic audience response system, iClicker (MPS, Gordonsville, VA), in this age group.

RESULTS: The questionnaire completed by 75 kindergarteners and 66 first graders. For the first graders, questions involving healthy choices were answered correctly 78% of the time (range 8-94%) and had 84% agreement on repeat testing (range 64-93%). Questions on diabetes were answered correctly 79% of the time (range 65-94%) and had 85% agreement on repeat testing. Crohnbach's alpha was calculated to determine the reliability of the questionnaire: on the revised kindergarten questionnaire, this ranged from 0.79 to 0.81 on Day 1 and 0.84-0.97 on Day 5; for the first graders, this ranged 0.79-0.81 on Day 1 and 0.84-0.97 on Day 5. Both kindergarteners and first graders answered the simplest of the basic knowledge questions correctly > 80% of the time, with acceptable test-retest agreement. Additionally, these children demonstrated acceptable understanding of the use of the iClicker classroom response system.}, } @article {pmid29615104, year = {2018}, author = {Nkeck, JR and Singwé Ngandeu, M and Ama Moor, V and Nkeck, JP and Chedjou, JP and Ndoadoumgue, AL and Mbacham, WF}, title = {Genetic analysis for rs2280205 (A>G) and rs2276961 (T>C) in SLC2A9 polymorphism for the susceptibility of gout in Cameroonians: a pilot study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {230}, pmid = {29615104}, issn = {1756-0500}, mesh = {Aged ; Cameroon ; Case-Control Studies ; Female ; Genetic Predisposition to Disease ; Glucose Transport Proteins, Facilitative/*genetics ; Gout/diagnosis/*genetics ; Humans ; Male ; Middle Aged ; Pilot Projects ; Polymerase Chain Reaction ; Polymorphism, Single Nucleotide ; }, abstract = {OBJECTIVE: To determine the association of non-synonymous variants rs2280205 and rs2276961 of the SLC2A9 gene to gout in Cameroonians.

RESULTS: In a case-control study including 30 patients with acute gout matched to 30 healthy volunteers. We searched for polymorphism of the targeted variants using Restriction Fragment Length Polymorphism following polymerize chain reaction. Fisher exact test and Student t-test were used to compare variables, with a threshold of significance set at 0.05. The mean age of participants was 58 ± 8 years with 28 (93%) males. The family history of gout was found in one-third of the cases (p > 0.05). Uricemia was higher in cases than controls (p < 0.001) but 24 h urate excretion was similar in both groups (p > 0.05). Ancestral alleles (G and C) and their homozygous genotypes (GG and CC) of the targeted variants were predominant in both groups (p < 0.001). The polymorphisms of targeted variants were not associated with gout, and do not influence uric acid concentration in blood and urine. Non-synonymous variants rs2280205 and rs2276961 are not associated with gout in Cameroonians. However, the hereditary component of the disease suggests the influence of other genetic and/or environmental factors.}, } @article {pmid29615102, year = {2018}, author = {Yusuf, D and Christy, J and Owen, D and Ho, M and Li, D and Fishman, MJ}, title = {A case report of nifedipine-induced hepatitis with jaundice.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {228}, pmid = {29615102}, issn = {1756-0500}, mesh = {Aged ; Calcium Channel Blockers/*adverse effects ; Chemical and Drug Induced Liver Injury/diagnosis/*etiology ; Female ; Hepatitis/diagnosis/*etiology ; Humans ; Jaundice/*chemically induced ; Nifedipine/*adverse effects ; }, abstract = {BACKGROUND: Nifedipine is a generic, well-known and commonly-prescribed dihydropyridine calcium channel blocker used in the treatment of hypertension and Prinzmetal's angina. A known but very rare and serious adverse effect of nifedipine is clinically-apparent hepatitis which can take months to resolve.

CASE PRESENTATION: Here we present a case of nifedipine-induced hepatitis in a 78-year-old Caucasian female with no prior history of liver or autoimmune disease. We discuss our investigative and management approach, and present a review of prior cases. We offer an approach for patients who present with signs of acute liver injury with jaundice and high elevations in serum transaminases.

CONCLUSION: Not much is known about nifedipine-induced hepatitis due to its rare occurrence. Its prevalence is unknown. The disease appears to afflict older men and women. It can present acutely (within days) or subacutely (within 4-8 weeks after medication start) and in an idiosyncratic manner. Chronic or latent cases have also been described, some diagnosed as late as 3 years after medication start. Common symptoms include jaundice, nausea, chills, rigors, diaphoresis, fatigue, and abdominal pain. Laboratory investigations often reveal profound elevations in AST, ALT, GGT, and conjugated bilirubin. Peripheral blood smear may demonstrate eosinophilia. Histology from liver biopsy typically demonstrates infiltration of immune cells, cholestasis, and a picture of steatohepatitis. Treatment involves immediate discontinuation of the drug with supportive care. Thus far, all published instances of nifedipine-induced hepatitis were self-limiting without mortality due to fulminant liver failure. However, this disease can take months to resolve. There is no randomized evidence for other treatments such as corticosteroids.}, } @article {pmid29615096, year = {2018}, author = {Han, J and Enyindah-Asonye, G and Lin, F and Smith, JD}, title = {CD6 expression has no effect on atherosclerosis in apolipoprotein E-deficient mice.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {229}, pmid = {29615096}, issn = {1756-0500}, support = {P01 HL029582/HL/NHLBI NIH HHS/United States ; P01 HL029582//National Institutes of Health/ ; }, mesh = {Animals ; *Antigens, CD ; *Antigens, Differentiation, T-Lymphocyte ; Aorta/pathology ; Apolipoproteins E/*deficiency ; Atherosclerosis/*blood/*pathology ; *B-Lymphocytes ; *Diet, Atherogenic ; Disease Models, Animal ; Female ; Male ; Mice ; Mice, Inbred DBA ; Mice, Knockout ; }, abstract = {OBJECTIVE: To determine if deficiency of CD6, a cell surface protein on lymphocytes that alters natural antibody production, increases atherosclerosis in ApoE-deficient mice fed a chow or a western-type diet.

RESULTS: We compared cholesterol levels, IgM, B1a cells, and aortic root lesion areas in ApoE-deficient vs. CD6/ApoE double deficient mice. Feeding the high-fat western type diet increased all parameters, except for B1a cell numbers decreased. Sex also had an effect on many parameters with males having increased body weights, higher high density lipoprotein cholesterol, higher B1a cells, but smaller atherosclerotic lesions if chow fed mice; however, this sex effect on atherosclerosis was absent in mice fed the western-type diet. CD6 deficiency had no effect on atherosclerosis in both male and female mice on either diet. Thus, loss of CD6 on lymphocytes did not lead to expected reductions in B1a cells and protective IgM levels, and in turn did not alter atherosclerosis in mice.}, } @article {pmid29615091, year = {2018}, author = {Nkoke, C and Dzudie, A and Makoge, C and Luchuo, EB and Jingi, AM and Kingue, S}, title = {Rheumatic heart disease in the South West region of Cameroon: a hospital based echocardiographic study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {221}, pmid = {29615091}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cameroon/epidemiology ; Echocardiography ; Female ; Hospitals/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Rheumatic Heart Disease/*diagnosis/*epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Rheumatic heart disease (RHD) prevails as a major public health problem in sub-Saharan Africa. In Cameroon, reports on RHD have been so far limited to a few cities. We sought to describe the demographic, clinical and echocardiographic features of rheumatic heart disease in the Buea Regional Hospital, South West region of Cameroon. Echocardiography reports between June 2016 and June 2017 were reviewed. The diagnosis of RHD was based on the World Heart Federation Criteria for the diagnosis of RHD.

RESULTS: A total of 669 echocardiograms were performed over the 1 year study period. Twenty-one (3.1%) had a definite echocardiographic diagnosis of RHD. There were 14 (66.7%) females. The age range was 13-94 years with a mean age of 47.8 ± 20.3 years. The most common indications for echocardiography were heart failure (47.6%), and dyspnea (42.9%). The mitral valve was the most commonly affected valve in 80.9% of cases. The most common valve lesion was isolated mitral stenosis (42.9%), followed by isolated mitral regurgitation (28.6%). There were no lesions on the tricuspid and pulmonic valves. Severe lesions were found in 80.9% of the patients. The complications were pulmonary hypertension (66.7%) and atrial fibrillation (9.5%).}, } @article {pmid29615037, year = {2018}, author = {Yang, F and Wang, M and Zhang, B and Xiang, W and Zhang, K and Chu, M and Wang, P}, title = {Identification of new progestogen-associated networks in mammalian ovulation using bioinformatics.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {36}, pmid = {29615037}, issn = {1752-0509}, support = {2014-2573//National Biological Breeding Capacity Building and Industrialization Projects/ ; 31372287//National Natural Science Foundation of China/ ; 2014ZX0800952B//Ministry of Agriculture transgenic major projects of China/ ; ASTIP-IAS13//Agricultural Science and Technology Innovation Program of China/ ; }, abstract = {BACKGROUND: Progesterone plays an essential role in mammalian ovulation. Although much is known about this process, the gene networks involved in ovulation have yet to be established. When analyze the mechanisms of ovulation, we often need to determine key genes or pathways to investigate the reproduction features. However, traditional experimental methods have a number of limitations.

RESULTS: Data, in this study, were acquired from GSE41836 and GSE54584 which provided different samples. They were analyzed with the GEO2R and 546 differentially expressed genes were obtained from two data sets using bioinformatics (absolute log2 FC > 1, P < 0.05). This study identified four genes (PGR, RELN, PDE10A and PLA2G4A) by protein-protein interaction networks and pathway analysis, and their functional enrichments were associated with ovulation. Then, the top 25 statistical pathway enrichments related to hCG treatment were analyzed. Furthermore, gene network analysis identified certain interconnected genes and pathways involved in progestogenic mechanisms, including progesterone-mediated oocyte maturation, the MAPK signaling pathway, the GnRH signaling pathway and focal adhesion, etc. Moreover, we explored the four target gene pathways. q-PCR analysis following hCG and RU486 treatments confirmed the certain novel progestogenic-associated genes (GNAI1, PRKCA, CAV1, EGFR, RHOA, ZYX, VCL, GRB2 and RAP1A).

CONCLUSIONS: The results suggested four key genes, nine predicted genes and eight pathways to be involved in progestogenic networks. These networks provide important regulatory genes and signaling pathways which are involved in ovulation. This study provides a fundamental basis for subsequent functional studies to investigate the regulation of mammalian ovulation.}, } @article {pmid29615030, year = {2018}, author = {Zecena, H and Tveit, D and Wang, Z and Farhat, A and Panchal, P and Liu, J and Singh, SJ and Sanghera, A and Bainiwal, A and Teo, SY and Meyskens, FL and Liu-Smith, F and Filipp, FV}, title = {Systems biology analysis of mitogen activated protein kinase inhibitor resistance in malignant melanoma.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {33}, pmid = {29615030}, issn = {1752-0509}, support = {GRC-13//University of California Senate Graduate Research Council/ ; K07 CA160756/CA/NCI NIH HHS/United States ; K99 CA154887/CA/NCI NIH HHS/United States ; CA154887//National Cancer Institute/ ; HSRI//Health Science Research Institute/ ; R00 CA154887/CA/NCI NIH HHS/United States ; CRN-17-427258//University of California, Cancer Research Coordinating Committee/ ; CA160756//National Cancer Institute/ ; GRFP//National Science Foundation/ ; }, abstract = {BACKGROUND: Kinase inhibition in the mitogen activated protein kinase (MAPK) pathway is a standard therapy for cancer patients with activating BRAF mutations. However, the anti-tumorigenic effect and clinical benefit are only transient, and tumors are prone to treatment resistance and relapse. To elucidate mechanistic insights into drug resistance, we have established an in vitro cellular model of MAPK inhibitor resistance in malignant melanoma.

METHODS: The cellular model evolved in response to clinical dosage of the BRAF inhibitor, vemurafenib, PLX4032. We conducted transcriptomic expression profiling using RNA-Seq and RT-qPCR arrays. Pathways of melanogenesis, MAPK signaling, cell cycle, and metabolism were significantly enriched among the set of differentially expressed genes of vemurafenib-resistant cells vs control. The underlying mechanism of treatment resistance and pathway rewiring was uncovered to be based on non-genomic adaptation and validated in two distinct melanoma models, SK-MEL-28 and A375. Both cell lines have activating BRAF mutations and display metastatic potential.

RESULTS: Downregulation of dual specific phosphatases, tumor suppressors, and negative MAPK regulators reengages mitogenic signaling. Upregulation of growth factors, cytokines, and cognate receptors triggers signaling pathways circumventing BRAF blockage. Further, changes in amino acid and one-carbon metabolism support cellular proliferation despite MAPK inhibitor treatment. In addition, treatment-resistant cells upregulate pigmentation and melanogenesis, pathways which partially overlap with MAPK signaling. Upstream regulator analysis discovered significant perturbation in oncogenic forkhead box and hypoxia inducible factor family transcription factors.

CONCLUSIONS: The established cellular models offer mechanistic insight into cellular changes and therapeutic targets under inhibitor resistance in malignant melanoma. At a systems biology level, the MAPK pathway undergoes major rewiring while acquiring inhibitor resistance. The outcome of this transcriptional plasticity is selection for a set of transcriptional master regulators, which circumvent upstream targeted kinases and provide alternative routes of mitogenic activation. A fine-woven network of redundant signals maintains similar effector genes allowing for tumor cell survival and malignant progression in therapy-resistant cancer.}, } @article {pmid29615023, year = {2018}, author = {Darwell, CT and Segar, ST and Cook, JM}, title = {Conserved community structure and simultaneous divergence events in the fig wasps associated with Ficus benjamina in Australia and China.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {13}, pmid = {29615023}, issn = {1472-6785}, support = {(#NE/G523912/1)//Natural Environment Research Council/International ; 15-24571S//Grantová Agentura České Republiky/International ; }, abstract = {BACKGROUND: Localised patterns of species diversity can be influenced by many factors, including regional species pools, biogeographic features and interspecific interactions. Despite recognition of these issues, we still know surprisingly little about how invertebrate biodiversity is structured across geographic scales. In particular, there have been few studies of how insect communities vary geographically while using the same plant host. We compared the composition (species, genera) and functional structure (guilds) of the chalcid wasp communities associated with the widespread fig tree, Ficus benjamina, towards the northern (Hainan province, China) and southern (Queensland, Australia) edges of its natural range. Sequence data were generated for nuclear and mtDNA markers and used to delimit species, and Bayesian divergence analyses were used to test patterns of community cohesion through evolutionary time.

RESULTS: Both communities host at least 14 fig wasp species, but no species are shared across continents. Community composition is similar at the genus level, with six genera shared although some differ in species diversity between China and Australia; a further three genera occur in only China or Australia. Community functional structure remains very similar in terms of numbers of species in each ecological guild despite community composition differing a little (genera) or a lot (species), depending on taxonomic level. Bayesian clustering analyses favour a single community divergence event across continents over multiple events for different ecological guilds. Molecular dating estimates of lineage splits between nearest inter-continental species pairs are broadly consistent with a scenario of synchronous community divergence from a shared "ancestral community".

CONCLUSIONS: Fig wasp community structure and genus-level composition are largely conserved in a wide geographic comparison between China and Australia. Moreover, dating analyses suggest that the functional community structure has remained stable for long periods during historic range expansions. This suggests that ecological interactions between species may play a persistent role in shaping these communities, in contrast to findings in some comparable temperate systems.}, } @article {pmid29614975, year = {2018}, author = {Zhang, L and Guo, K and Zhang, GZ and Lin, LH and Ji, X}, title = {Evolutionary transitions in body plan and reproductive mode alter maintenance metabolism in squamates.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {45}, pmid = {29614975}, issn = {1471-2148}, support = {31470471, 31301878, 31300339 and 31272294//National Natural Science Foundation of China/International ; KYLX_0715//Innovation Program of Jiangsu Province for Graduate Students/International ; SBK2016020667//Natural Science Foundation of Jiangsu Province/International ; }, mesh = {Analysis of Variance ; Animals ; *Biological Evolution ; Body Weight ; Female ; Least-Squares Analysis ; Lizards/*anatomy & histology/*physiology ; Phylogeny ; Reproduction/*physiology ; Temperature ; }, abstract = {BACKGROUND: Energy (resources) acquired by animals should be allocated towards competing demands, maintenance, growth, reproduction and fat storage. Reproduction has the second lowest priority in energy allocation and only is allowed after meeting the energetic demands for maintenance and growth. This hierarchical allocation of energy suggests the hypothesis that species or taxa with high maintenance costs would be less likely to invest more energy in reproduction or to evolve an energetically more expensive mode of reproduction. Here, we used data on standard metabolic rate so far reported for 196 species of squamates to test this hypothesis.

RESULTS: We found that maintenance costs were lower in snakes than in lizards, and that the costs were lower in viviparous species than in oviparous species. As snakes generally invest more energy per reproductive episode than lizards, and viviparity is an energetically more expensive mode of reproduction than oviparity, our results are consistent with the hypothesis tested.

CONCLUSION: The transition from lizard-like to snake-like body form and the transition from oviparity to viviparity are major evolutionary transitions in vertebrates, which likely alter many aspects of biology of the organisms involved. Our study is the first to demonstrate that evolutionary transitions in body plan and reproductive mode alter maintenance metabolism in squamates.}, } @article {pmid29614974, year = {2018}, author = {Zhang, Z and An, M and Miao, J and Gu, Z and Liu, C and Zhong, B}, title = {The Antarctic sea ice alga Chlamydomonas sp. ICE-L provides insights into adaptive patterns of chloroplast evolution.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {53}, pmid = {29614974}, issn = {1471-2229}, support = {31570219//National Natural Science Foundation of China (CN)/ ; 16KJA180002//Jiangsu Province Key Project for Scientific Research/ ; 16KJA180002//Six Talent Peaks Project of Jiangsu Province/ ; }, mesh = {Antarctic Regions ; Chlamydomonas/metabolism/*physiology ; Chloroplasts/metabolism/*physiology ; Photosynthesis/physiology ; }, abstract = {BACKGROUND: The ice alga Chlamydomonas sp. ICE-L is the main contributor to primary productivity in Antarctic sea ice ecosystems and is well adapted to the extremely harsh environment. However, the adaptive mechanism of Chlamydomonas sp. ICE-L to sea-ice environment remains unclear. To study the adaptive strategies in Chlamydomonas sp. ICE-L, we investigated the molecular evolution of chloroplast photosynthetic genes that are essential for the accumulation of carbohydrate and energy living in Antarctic sea ice.

RESULTS: The 60 chloroplast protein-coding genes of Chlamydomonas sp. ICE-L were obtained, and the branch-site test detected significant signatures of positive selection on atpB, psaB, and rbcL genes in Chlamydomonas sp. ICE-L associated with the photosynthetic machinery. These positively selected genes were further identified as being under convergent evolution between Chlamydomonas sp. ICE-L and the halotolerant alga Dunaliella salina.

CONCLUSIONS: Our study provides evidence that the phototrophic component of Chlamydomonas sp. ICE-L exhibits adaptive evolution under extreme environment. The positive Darwinian selection operates on the chloroplast protein-coding genes of Antarctic ice algae adapted to extreme environment following functional-specific and lineages-specific patterns. In addition, three positively selected genes with convergent substitutions in Chlamydomonas sp. ICE-L were identified, and the adaptive modifications in these genes were in functionally important regions of the proteins. Our study provides a foundation for future experiments on the biochemical and physiological impacts of photosynthetic genes in green algae.}, } @article {pmid29614966, year = {2018}, author = {Stadnicka, K and Sławińska, A and Dunisławska, A and Pain, B and Bednarczyk, M}, title = {Molecular signatures of epithelial oviduct cells of a laying hen (Gallus gallus domesticus) and quail (Coturnix japonica).}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {9}, pmid = {29614966}, issn = {1471-213X}, support = {UMO-2011/03/N/NZ9/03814//National Science Centre Poland/International ; POLONIUM 2015-2017 granted to Professor Marek Bednarczyk and Dr Bertrand Pain//Ministerstwo Nauki i Szkolnictwa Wyższego (PL), Ministry of Foreign Affairs of the Republic of Poland/International ; PBS3/A8/30/2015//Narodowe Centrum Badań i Rozwoju/International ; }, abstract = {BACKGROUND: In this work we have determined molecular signatures of oviduct epithelial and progenitor cells. We have proposed a panel of selected marker genes, which correspond with the phenotype of oviduct cells of a laying hen (Gallus gallus domesticus) and quail (Coturnix japonica). We demonstrated differences in characteristics of those cells, in tissue and in vitro, with respect to different anatomical and functional parts of the oviduct (infundibulum (INF), distal magnum (DM, and proximal magnum (PM)). The following gene expression signatures were studied: (1) oviduct markers (estrogen receptor 1, ovalbumin, and SPINK7 - ovomucoid), (2) epithelial markers (keratin 5, keratin 14, and occludin) and (3) stem-like/progenitor markers (CD44 glycoprotein, LGR5, Musashi-1, and sex determining region Y-box 9, Nanog homebox, OCT4/cPOUV gene encoding transcription factor POU5F3).

RESULTS: In chicken, the expression of oviduct markers increased toward the proximal oviduct. Epithelial markers keratin14 and occludin were high in distal oviduct and decreased toward the proximal magnum. In quail oviduct tissue, the gene expression pattern of oviduct/epithelial markers was similar to chicken. The markers of progenitors/stemness in hen oviduct (Musashi-1 and CD44 glycoprotein) had the highest relative expression in the infundibulum and decreased toward the proximal magnum. In quail, we found significant expression of four progenitor markers (LGR5 gene, SRY sex determining region Y-box 9, OCT4/cPOUV gene, and CD44 glycoprotein) that were largely present in the distal oviduct. After in vitro culture of oviduct cells, the gene expression pattern has changed. High secretive potential of magnum-derived cells diminished by using decreased abundance of mRNA. On the other hand, chicken oviduct cells originating from the infundibulum gained ability to express OVM and OVAL. Epithelial character of the cells was maintained in vitro. Among progenitor markers, both hen and quail cells expressed high level of SOX9, LGR5 and Musashi-1.

CONCLUSION: Analysis of tissue material revealed gradual increase/decrease pattern in majority of the oviduct markers in both species. This pattern changed after the oviductal cells have been cultured in vitro. The results can provide molecular tools to validate the phenotype of in vitro biological models from reproductive tissue.}, } @article {pmid29614961, year = {2018}, author = {Manzanilla, V and Kool, A and Nguyen Nhat, L and Nong Van, H and Le Thi Thu, H and de Boer, HJ}, title = {Phylogenomics and barcoding of Panax: toward the identification of ginseng species.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {44}, pmid = {29614961}, issn = {1471-2148}, support = {VAST02.01/16-17//Vietnam Academy of Science/International ; 606895//Marie-Curie ITN/International ; }, mesh = {Base Sequence ; Bayes Theorem ; DNA Barcoding, Taxonomic/*methods ; DNA Methylation/genetics ; Genome, Mitochondrial ; *Genome, Plastid ; *Genomics ; High-Throughput Nucleotide Sequencing ; Microbiota ; Panax/*genetics ; *Phylogeny ; Species Specificity ; }, abstract = {BACKGROUND: The economic value of ginseng in the global medicinal plant trade is estimated to be in excess of US$2.1 billion. At the same time, the evolutionary placement of ginseng (Panax ginseng) and the complex evolutionary history of the genus is poorly understood despite several molecular phylogenetic studies. In this study, we use a full plastome phylogenomic framework to resolve relationships in Panax and to identify molecular markers for species discrimination.

RESULTS: We used high-throughput sequencing of MBD2-Fc fractionated Panax DNA to supplement publicly available plastid genomes to create a phylogeny based on fully assembled and annotated plastid genomes from 60 accessions of 8 species. The plastome phylogeny based on a 163 kbp matrix resolves the sister relationship of Panax ginseng with P. quinquefolius. The closely related species P. vietnamensis is supported as sister of P. japonicus. The plastome matrix also shows that the markers trnC-rps16, trnS-trnG, and trnE-trnM could be used for unambiguous molecular identification of all the represented species in the genus.

CONCLUSIONS: MBD2 depletion reduces the cost of plastome sequencing, which makes it a cost-effective alternative to Sanger sequencing based DNA barcoding for molecular identification. The plastome phylogeny provides a robust framework that can be used to study the evolution of morphological characters and biosynthesis pathways of ginsengosides for phylogenetic bioprospecting. Molecular identification of ginseng species is essential for authenticating ginseng in international trade and it provides an incentive for manufacturers to create authentic products with verified ingredients.}, } @article {pmid29614959, year = {2018}, author = {Lovell, PV and Huizinga, NA and Friedrich, SR and Wirthlin, M and Mello, CV}, title = {The constitutive differential transcriptome of a brain circuit for vocal learning.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {231}, pmid = {29614959}, issn = {1471-2164}, support = {R21_DC014432//National Institute on Deafness and Other Communication Disorders/ ; R24_GM120464//National Institute of General Medical Sciences/ ; NSF_143602//Directorate for Biological Sciences/ ; }, mesh = {Animals ; Avian Proteins/*genetics ; Brain/physiology ; Finches/*genetics/physiology ; Gene Expression Profiling/*veterinary ; Gene Expression Regulation ; Learning ; Male ; Multigene Family ; Oligonucleotide Array Sequence Analysis/veterinary ; Vocalization, Animal/*physiology ; }, abstract = {BACKGROUND: The ability to imitate the vocalizations of other organisms, a trait known as vocal learning, is shared by only a few organisms, including humans, where it subserves the acquisition of speech and language, and 3 groups of birds. In songbirds, vocal learning requires the coordinated activity of a set of specialized brain nuclei referred to as the song control system. Recent efforts have revealed some of the genes that are expressed in these vocal nuclei, however a thorough characterization of the transcriptional specializations of this system is still missing. We conducted a rigorous and comprehensive analysis of microarrays, and conducted a separate analysis of 380 genes by in situ hybridizations in order to identify molecular specializations of the major nuclei of the song system of zebra finches (Taeniopygia guttata), a songbird species.

RESULTS: Our efforts identified more than 3300 genes that are differentially regulated in one or more vocal nuclei of adult male birds compared to the adjacent brain regions. Bioinformatics analyses provided insights into the possible involvement of these genes in molecular pathways such as cellular morphogenesis, intrinsic cellular excitability, neurotransmission and neuromodulation, axonal guidance and cela-to-cell interactions, and cell survival, which are known to strongly influence the functional properties of the song system. Moreover, an in-depth analysis of specific gene families with known involvement in regulating the development and physiological properties of neuronal circuits provides further insights into possible modulators of the song system.

CONCLUSION: Our study represents one of the most comprehensive molecular characterizations of a brain circuit that evolved to facilitate a learned behavior in a vertebrate. The data provide novel insights into possible molecular determinants of the functional properties of the song control circuitry. It also provides lists of compelling targets for pharmacological and genetic manipulations to elucidate the molecular regulation of song behavior and vocal learning.}, } @article {pmid29614958, year = {2018}, author = {Woltering, JM and Holzem, M and Schneider, RF and Nanos, V and Meyer, A}, title = {The skeletal ontogeny of Astatotilapia burtoni - a direct-developing model system for the evolution and development of the teleost body plan.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {8}, pmid = {29614958}, issn = {1471-213X}, support = {293700//European Research Council/International ; }, abstract = {BACKGROUND: The experimental approach to the evolution and development of the vertebrate skeleton has to a large extent relied on "direct-developing" amniote model organisms, such as the mouse and the chicken. These organisms can however only be partially informative where it concerns secondarily lost features or anatomical novelties not present in their lineages. The widely used anamniotes Xenopus and zebrafish are "indirect-developing" organisms that proceed through an extended time as free-living larvae, before adopting many aspects of their adult morphology, complicating experiments at these stages, and increasing the risk for lethal pleiotropic effects using genetic strategies.

RESULTS: Here, we provide a detailed description of the development of the osteology of the African mouthbrooding cichlid Astatotilapia burtoni, primarily focusing on the trunk (spinal column, ribs and epicentrals) and the appendicular skeleton (pectoral, pelvic, dorsal, anal, caudal fins and scales), and to a lesser extent on the cranium. We show that this species has an extremely "direct" mode of development, attains an adult body plan within 2 weeks after fertilization while living off its yolk supply only, and does not pass through a prolonged larval period.

CONCLUSIONS: As husbandry of this species is easy, generation time is short, and the species is amenable to genetic targeting strategies through microinjection, we suggest that the use of this direct-developing cichlid will provide a valuable model system for the study of the vertebrate body plan, particularly where it concerns the evolution and development of fish or teleost specific traits. Based on our results we comment on the development of the homocercal caudal fin, on shared ontogenetic patterns between pectoral and pelvic girdles, and on the evolution of fin spines as novelty in acanthomorph fishes. We discuss the differences between "direct" and "indirect" developing actinopterygians using a comparison between zebrafish and A. burtoni development.}, } @article {pmid29614957, year = {2018}, author = {Chaintreuil, C and Perrier, X and Martin, G and Fardoux, J and Lewis, GP and Brottier, L and Rivallan, R and Gomez-Pacheco, M and Bourges, M and Lamy, L and Thibaud, B and Ramanankierana, H and Randriambanona, H and Vandrot, H and Mournet, P and Giraud, E and Arrighi, JF}, title = {Naturally occurring variations in the nod-independent model legume Aeschynomene evenia and relatives: a resource for nodulation genetics.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {54}, pmid = {29614957}, issn = {1471-2229}, support = {ANR-AeschyNod-14-CE19-0005-01//ANR/ ; }, mesh = {Bradyrhizobium/physiology ; Diploidy ; Fabaceae/genetics/*metabolism/*microbiology ; Genome, Plant/*genetics ; Genotype ; Ploidies ; Polyploidy ; Symbiosis/genetics/physiology ; }, abstract = {BACKGROUND: Among semi-aquatic species of the legume genus Aeschynomene, some have the unique property of being root and stem-nodulated by photosynthetic Bradyrhizobium lacking the nodABC genes necessary for the production of Nod factors. These species provide an excellent biological system with which to explore the evolution of nodulation in legumes. Among them, Aeschynomene evenia has emerged as a model legume to undertake the genetic dissection of the so-called Nod-independent symbiosis. In addition to the genetic analysis of nodulation on a reference line, natural variation in a germplasm collection could also be surveyed to uncover genetic determinants of nodulation. To this aim, we investigated the patterns of genetic diversity in a collection of 226 Nod-independent Aeschynomene accessions.

RESULTS: A combination of phylogenetic analyses, comprising ITS and low-copy nuclear genes, along with cytogenetic experiments and artificial hybridizations revealed the richness of the Nod-independent Aeschynomene group with the identification of 13 diploid and 6 polyploid well-differentiated taxa. A set of 54 SSRs was used to further delineate taxon boundaries and to identify different genotypes. Patterns of microsatellite diversity also illuminated the genetic basis of the Aeschynomene taxa that were all found to be predominantly autogamous and with a predicted simple disomic inheritance, two attributes favorable for genetics. In addition, taxa displaying a pronounced genetic diversity, notably A. evenia, A. indica and A. sensitiva, were characterized by a clear geographically-based genetic structure and variations in root and stem nodulation.

CONCLUSION: A well-characterized germplasm collection now exists as a major genetic resource to thoroughly explore the natural variation of nodulation in response to different bradyrhizobial strains. Symbiotic polymorphisms are expected to be found notably in the induction of nodulation, in nitrogen fixation and also in stem nodulation. Subsequent genetic analysis and locus mapping will pave the way for the identification of the underlying genes through forward or reverse genetics. Such discoveries will significantly contribute to our understanding of the molecular mechanisms underpinning how some Aeschynomene species can be efficiently nodulated in a Nod-independent fashion.}, } @article {pmid29614956, year = {2018}, author = {Schmid, M and Wellmann, R and Bennewitz, J}, title = {Power and precision of QTL mapping in simulated multiple porcine F2 crosses using whole-genome sequence information.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {22}, pmid = {29614956}, issn = {1471-2156}, abstract = {BACKGROUND: During the last two decades, many QTL (quantitative trait locus) mapping experiments in pigs have been conducted using F2 crosses established from two outbred founder breeds. The founder breeds were frequently chosen from the Asian and European type breeds. A combination of next-generation sequencing, SNP (single nucleotide polymorphism) genotyping technology using SNP-chips, and genotype imputation techniques, can be used to infer the sequence information of all F2 individuals in a cost-effective way. The aim of the present simulation study was to analyze the power and precision of genome-wide association studies (GWASs) with whole-genome sequence data in several types of F2 crosses, including pooled crosses.

METHODS: Based on a common historical population, three breeds representing two European type breeds (EU1 and EU2) and one Asian type breed (AS) were simulated. Two F2 designs of 500 individuals each were simulated. The cross EU1xEU2 (ASxEU2) was simulated using the phylogenetically closely related breeds EU1 and EU2 (or distantly related breeds AS and EU2) as the founder breeds. The simulated genomes comprised ten chromosomes, each with a length of 1 Morgan and whole-genome sequence information. A polygenic trait with a heritability of 0.5, which was affected by approximately 20 QTL per Morgan, was simulated. GWASs were conducted using single marker mixed linear models, either within the crosses or in their pooled datasets. Additionally, the studies were conducted in the breed EU2, which was a founder breed in both simulated crosses.

RESULTS: The power to map QTL was high (low) in the ASxEU2 (EU1xEU2) cross and was highest when the data of both crosses were analyzed jointly. By contrast, the mapping precision was the highest in the EU1xEU2 cross. Pooling data led to a precision that was in between the precision of the EU1xEU2 cross and the ASxEU2 cross. A higher mapping precision was observed for QTL segregating within a founder breed.

CONCLUSIONS: These results suggest that the existing F2 crosses are promising databases for QTL mapping when the founder breeds are closely related or several crosses can be pooled. This conclusion is particularly applicable for QTL that segregate in a founder breed.}, } @article {pmid29614954, year = {2018}, author = {Huang, KYY and Huang, YJ and Chen, PY}, title = {BS-Seeker3: ultrafast pipeline for bisulfite sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {111}, pmid = {29614954}, issn = {1471-2105}, support = {MOST-103-2313-B-001-003-MY3//Ministry of Science and Technology, Taiwan/International ; 104-2923-B-001 -003 -MY2//Ministry of Science and Technology, Taiwan/International ; 106-2311-B-001 -035 -MY3//Ministry of Science and Technology, Taiwan/International ; }, mesh = {Computational Biology/*methods ; DNA Methylation ; *Epigenesis, Genetic ; Epigenomics/*methods ; Genome, Human ; High-Throughput Nucleotide Sequencing ; Humans ; Sequence Analysis, DNA/*methods ; *Software ; Sulfites/*chemistry ; }, abstract = {BACKGROUND: DNA methylation is an important epigenetic modification critical in regulation and transgenerational inheritance. The methylation level can be estimated at single-nucleotide resolution by whole-genome bisulfite sequencing (BS-seq; WGBS). Current bisulfite aligners provide pipelines for processing the reads by WGBS; however, few are able to analyze the BS-seqs in a reasonable timeframe that meets the needs of the rapid expansion of epigenome sequencing in biomedical research.

RESULTS: We introduce BS-Seeker3, an extensively improved and optimized implementation of BS-Seeker2 that leverages the available computational power of a standard bioinformatics lab. BS-Seeker3 adopts all alignment features of BS-Seeker2. It performs ultrafast alignments and achieves both high accuracy and high mappability, more than twice that of the other aligners that we evaluated. Moreover, BS Seeker 3 is well linked with downstream analyzer MethGo for up to 9 types of genomic and epigenomic analyses.

CONCLUSIONS: BS-Seeker3 is an accurate, versatile, ultra-fast pipeline for processing bisulfite-converted reads. It also helps the user better visualize the methylation data.}, } @article {pmid29614953, year = {2018}, author = {de Gouvêa, PF and Bernardi, AV and Gerolamo, LE and de Souza Santos, E and Riaño-Pachón, DM and Uyemura, SA and Dinamarco, TM}, title = {Transcriptome and secretome analysis of Aspergillus fumigatus in the presence of sugarcane bagasse.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {232}, pmid = {29614953}, issn = {1471-2164}, support = {2014/10466-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Aspergillus fumigatus/genetics/*growth & development/metabolism ; Cellulases/genetics/metabolism ; Cellulose/*chemistry ; Chromatography, Liquid ; Fructose/chemistry ; Fungal Proteins/*genetics/*metabolism ; Gene Expression Profiling/*methods ; Glucan Endo-1,3-beta-D-Glucosidase/genetics/metabolism ; Glycoside Hydrolases/genetics/metabolism ; Saccharum/metabolism ; Sequence Analysis, RNA/methods ; Tandem Mass Spectrometry ; Xylosidases/genetics/metabolism ; }, abstract = {BACKGROUND: Sugarcane bagasse has been proposed as a lignocellulosic residue for second-generation ethanol (2G) produced by breaking down biomass into fermentable sugars. The enzymatic cocktails for biomass degradation are mostly produced by fungi, but low cost and high efficiency can consolidate 2G technologies. A. fumigatus plays an important role in plant biomass degradation capabilities and recycling. To gain more insight into the divergence in gene expression during steam-exploded bagasse (SEB) breakdown, this study profiled the transcriptome of A. fumigatus by RNA sequencing to compare transcriptional profiles of A. fumigatus grown on media containing SEB or fructose as the sole carbon source. Secretome analysis was also performed using SDS-PAGE and LC-MS/MS.

RESULTS: The maximum activities of cellulases (0.032 U mL-1), endo-1,4-β--xylanase (10.82 U mL-1) and endo-1,3-β glucanases (0.77 U mL-1) showed that functional CAZymes (carbohydrate-active enzymes) were secreted in the SEB culture conditions. Correlations between transcriptome and secretome data identified several CAZymes in A. fumigatus. Particular attention was given to CAZymes related to lignocellulose degradation and sugar transporters. Genes encoding glycoside hydrolase classes commonly expressed during the breakdown of cellulose, such as GH-5, 6, 7, 43, 45, and hemicellulose, such as GH-2, 10, 11, 30, 43, were found to be highly expressed in SEB conditions. Lytic polysaccharide monooxygenases (LPMO) classified as auxiliary activity families AA9 (GH61), CE (1, 4, 8, 15, 16), PL (1, 3, 4, 20) and GT (1, 2, 4, 8, 20, 35, 48) were also differentially expressed in this condition. Similarly, the most important enzymes related to biomass degradation, including endoxylanases, xyloglucanases, β-xylosidases, LPMOs, α-arabinofuranosidases, cellobiohydrolases, endoglucanases and β-glucosidases, were also identified in the secretome.

CONCLUSIONS: This is the first report of a transcriptome and secretome experiment of Aspergillus fumigatus in the degradation of pretreated sugarcane bagasse. The results suggest that this strain employs important strategies for this complex degradation process. It was possible to identify a set of genes and proteins that might be applied in several biotechnology fields. This knowledge can be exploited for the improvement of 2G ethanol production by the rational design of enzymatic cocktails.}, } @article {pmid29614952, year = {2018}, author = {Yao, Y and Enkhtsetseg, S and Odsbu, I and Fan, L and Morigen, M}, title = {Mutations of DnaA-boxes in the oriR region increase replication frequency of the MiniR1-1 plasmid.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {27}, pmid = {29614952}, issn = {1471-2180}, abstract = {BACKGROUND: The MiniR1-1 plasmid is a derivative of the R1 plasmid, a low copy cloning vector.

RESULTS: Nucleotide sequencing analysis shows that the MiniR1-1 plasmid is a 6316 bp circular double-stranded DNA molecule with an oriR1 (origin for replication). The plasmid carries the repA, tap, copA and bla genes, and genes for ORF1 and ORF2. MiniR1-1 contains eight DnaA-binding sites (DnaA-boxes). DnaA-box1 is in the oriR1 region and fully matched to the DnaA-box consensus sequence, and DnaA-box8, with one mismatch, is close to the copA gene. The presence of the MiniR1-1 plasmid leads to an accumulation of the D-period cells and an increase in cell size of slowly growing Escherichia coli cells, suggesting that the presence of MiniR1-1 delays cell division. Mutations in the MiniR1-1 DnaA-box1 and DnaA-box8 significantly increase the copy number of the plasmid and the mutations in DnaA-box1 also affect cell size. It is likely that titration of DnaA to DnaA-boxes negatively controls replication of the MiniR1-1 plasmid and delays cell division. Interestingly, DnaA weakly interacts with the initiator protein RepA in vivo.

CONCLUSION: DnaA regulates the copy number of MiniR1-1 as a negative factor through interacting with the RepA protein.}, } @article {pmid29614950, year = {2018}, author = {van Hooft, P and Keet, DF and Brebner, DK and Bastos, ADS}, title = {Genetic insights into dispersal distance and disperser fitness of African lions (Panthera leo) from the latitudinal extremes of the Kruger National Park, South Africa.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {21}, pmid = {29614950}, issn = {1471-2156}, support = {UID78566//National Research Foundation/ ; }, abstract = {BACKGROUND: Female lions generally do not disperse far beyond their natal range, while males can disperse distances of over 200 km. However, in bush-like ecosystems dispersal distances less than 25 km are reported. Here, we investigate dispersal in lions sampled from the northern and southern extremes of Kruger National Park, a bush-like ecosystem in South Africa where bovine tuberculosis prevalence ranges from low to high across a north-south gradient.

RESULTS: A total of 109 individuals sampled from 1998 to 2004 were typed using 11 microsatellite markers, and mitochondrial RS-3 gene sequences were generated for 28 of these individuals. Considerable north-south genetic differentiation was observed in both datasets. Dispersal was male-biased and generally further than 25 km, with long-distance male gene flow (75-200 km, detected for two individuals) confirming that male lions can travel large distances, even in bush-like ecosystems. In contrast, females generally did not disperse further than 20 km, with two distinctive RS-3 gene clusters for northern and southern females indicating no or rare long-distance female dispersal. However, dispersal rate for the predominantly non-territorial females from southern Kruger (fraction dispersers ≥0.68) was higher than previously reported. Of relevance was the below-average body condition of dispersers and their low presence in prides, suggesting low fitness.

CONCLUSIONS: Large genetic differences between the two sampling localities, and low relatedness among males and high dispersal rates among females in the south, suggestive of unstable territory structure and high pride turnover, have potential implications for spread of diseases and the management of the Kruger lion population.}, } @article {pmid29614345, year = {2018}, author = {Fan, Z and Zhou, A and Osada, N and Yu, J and Jiang, J and Li, P and Du, L and Niu, L and Deng, J and Xu, H and Xing, J and Yue, B and Li, J}, title = {Ancient hybridization and admixture in macaques (genus Macaca) inferred from whole genome sequences.}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {376-386}, doi = {10.1016/j.ympev.2018.03.038}, pmid = {29614345}, issn = {1095-9513}, support = {R00 HG005846/HG/NHGRI NIH HHS/United States ; }, abstract = {The evolutionary history of the stump-tailed macaque (Macaca arctoides) and its genetic relationship to other macaques is a subject of continuing controversy. Here, we have reported the first genome sequences of two stump-tailed macaques and one Assamese macaque (M. assamensis). Additionally, we have investigated the genetic diversity between macaque species and analyzed ancient hybridization events. Genome-wide analyses demonstrated that the stump-tailed macaque is more closely related to sinica species than to fascicularis/mulatta species. This topology contradicts the mitochondrial sequence-based phylogeny that places the stump-tailed macaque into the fascicularis/mulatta group. However, our results further show that stump-tailed macaques have genetic backgrounds distinct from sinica species, and present evidence of gene flows with rhesus macaques. We suggest that an ancient introgression occurred after stump-tailed macaques diverged from sinica species. The distinct gene flow between proto-arctoides and proto-mulatta resulted in the transfer of rhesus macaque-type mitochondria into proto-arctoides. The rhesus macaque-type mitochondria remained in populations because of genetic drift during the bottleneck. The PSMC results and morphological and geographic evidence are consistent with the mitochondria capture pattern in the stump-tailed macaque. The molecular clock estimates suggest that the mitochondrial transference into stump-tailed macaques occurred 0.4-1.4 million years ago. Furthermore, we detected extensive admixtures between different macaque species, indicating that gene flow has played an important role in the evolutionary history of the genus Macaca.}, } @article {pmid29614271, year = {2018}, author = {Dupin, E and Calloni, GW and Coelho-Aguiar, JM and Le Douarin, NM}, title = {The issue of the multipotency of the neural crest cells.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.03.024}, pmid = {29614271}, issn = {1095-564X}, abstract = {In the neural primordium of vertebrate embryos, the neural crest (NC) displays a unique character: the capacity of its component cells to leave the neural primordium, migrate along definite (and, for long, not identified) routes in the developing embryo and invade virtually all tissues and organs, while producing a large array of differentiated cell types. The most striking diversity of the NC derivatives is found in its cephalic domain that produces, not only melanocytes and peripheral nerves and ganglia, but also various mesenchymal derivatives (connective tissues, bones, cartilages…) which, in other parts of the body, are mesoderm-derived. The aim of this article was to review the large amount of work that has been devoted to solving the problem of the differentiation capacities of individual NC cells (NCC) arising from both the cephalic and trunk levels of the neural axis. A variety of experimental designs applied to NCC either in vivo or in vitro are evaluated, including the possibility to culture them in crestospheres, a technique previously designed for cells of the CNS, and which reinforces the notion, previously put forward, of the existence of NC stem cells. At the trunk level, the developmental potentialities of the NCC are more restricted than in their cephalic counterparts, but, in addition to the neural-melanocytic fate that they exclusively express in vivo, it was clearly shown that they harbor mesenchymal capacities that can be revealed in vitro. Finally, a large amount of evidence has been obtained that, during the migration process, most of the NCC are multipotent with a variable array of potentialities among the cells considered. Investigations carried out in adults have shown that multipotent NC stem cells persist in the various sites of the body occupied by NCC. Enlightening new developments concerning the invasive capacity of NCC, the growing peripheral nerves were revealed as migration routes for NCC travelling to distant ventrolateral regions of the body. Designated "Schwann cell precursors" in the mouse embryo, these NCC can leave the nerves and are able to convert to a novel fate. The convertibility of the NC-derived cells, particularly evident in the Schwann cell-melanocyte lineage transition, has also been demonstrated for neuroendocrine cells of the adult carotid body and for the differentiation of parasympathetic neurons of ganglia distant from their origin, the NC. All these new developments attest the vitality of the research on the NC, a field that characterizes vertebrate development and for which the interest has constantly increased during the last decades.}, } @article {pmid29614214, year = {2018}, author = {Sefbom, J and Kremp, A and Rengefors, K and Jonsson, PR and Sjöqvist, C and Godhe, A}, title = {A planktonic diatom displays genetic structure over small spatial scales.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2783-2795}, doi = {10.1111/1462-2920.14117}, pmid = {29614214}, issn = {1462-2920}, support = {215-2010-751//Swedish Research Council FORMAS/ ; 251564//Academy of Finland/ ; //Linnaeus Centre for Marine Evolutionary Biology at the University of Gothenburg through Swedish Research Council and FORMAS, through the projects BAMBI and BIO-C3/ ; //BONUS, the joint Baltic Sea research and development program (Art 185)/ ; //Oscar and Lilli Lamms Minne/ ; //Wilhelm och Martina Lundgrens Vetenskapsfond/ ; //Wåhlströms Minnesfond/ ; //Kapten Carl Stenholms Donationsfond/ ; }, abstract = {Marine planktonic microalgae have potentially global dispersal, yet reduced gene flow has been confirmed repeatedly for several species. Over larger distances (>200 km) geographic isolation and restricted oceanographic connectivity have been recognized as instrumental in driving population divergence. Here we investigated whether similar patterns, that is, structured populations governed by geographic isolation and/or oceanographic connectivity, can be observed at smaller (6-152 km) geographic scales. To test this we established 425 clonal cultures of the planktonic diatom Skeletonema marinoi collected from 11 locations in the Archipelago Sea (northern Baltic Sea). The region is characterized by a complex topography, entailing several mixing regions of which four were included in the sampling area. Using eight microsatellite markers and conventional F-statistics, significant genetic differentiation was observed between several sites. Moreover, Bayesian cluster analysis revealed the co-occurrence of two genetic groups spread throughout the area. However, geographic isolation and oceanographic connectivity could not explain the genetic patterns observed. Our data reveal hierarchical genetic structuring whereby despite high dispersal potential, significantly diverged populations have developed over small spatial scales. Our results suggest that biological characteristics and historical events may be more important in generating barriers to gene flow than physical barriers at small spatial scales.}, } @article {pmid29614213, year = {2018}, author = {Douglas, AE}, title = {What will it take to understand the ecology of symbiotic microorganisms?.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, pmid = {29614213}, issn = {1462-2920}, support = {R01 GM095372/GM/NIGMS NIH HHS/United States ; }, } @article {pmid29614212, year = {2018}, author = {Liu, JK and Chang, HW and Liu, Y and Qin, YH and Ding, YH and Wang, L and Zhao, Y and Zhang, MZ and Cao, SN and Li, LT and Liu, W and Li, GH and Qin, QM}, title = {The key gluconeogenic gene PCK1 is crucial for virulence of Botrytis cinerea via initiating its conidial germination and host penetration.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1794-1814}, doi = {10.1111/1462-2920.14112}, pmid = {29614212}, issn = {1462-2920}, abstract = {The process of initiation of host invasion and survival of some foliar phytopathogenic fungi in the absence of external nutrients on host leaf surfaces remains obscure. Here, we demonstrate that gluconeogenesis plays an important role in the process and nutrient-starvation adaptation before the pathogen host invasion. Deletion of phosphoenolpyruvate carboxykinase gene BcPCK1 in gluconeogenesis in Botrytis cinerea, the causative agent of grey mould, resulted in the failure of the ΔBcpck1 mutant conidia to germinate on hard and hydrophobic surface and penetrate host cells in the absence of glucose, reduction in conidiation and slow conidium germination in a nutrient-rich medium. The wild-type and ΔBcpck1 conidia germinate similarly in the presence of glucose (higher concentration) as the sole carbon source. Conidial glucose-content should reach a threshold level to initiate germination and host penetration. Infection structure formation by the mutants displayed a glucose-dependent fashion, which corresponded to the mutant virulence reduction. Exogenous glucose or complementation of BcPCK1 completely rescued all the developmental and virulence defects of the mutants. Our findings demonstrate that BcPCK1 plays a crucial role in B. cinerea pathogenic growth and virulence, and provide new insights into gluconeogenesis mediating pathogenesis of plant fungal pathogens via initiation of conidial germination and host penetration.}, } @article {pmid29614211, year = {2018}, author = {de la Torre, M and Gómez-Botrán, JL and Olivera, ER and Bermejo, F and Rodríguez-Morán, J and Luengo, JM}, title = {Histamine catabolism in Pseudomonas putida U: identification of the genes, catabolic enzymes and regulators.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1828-1841}, doi = {10.1111/1462-2920.14118}, pmid = {29614211}, issn = {1462-2920}, abstract = {In this study, the catabolic pathway required for the degradation of the biogenic amine histamine (Hin) was genetically and biochemically characterized in Pseudomonas putida U. The 11 proteins (HinABCDGHFLIJK) that participate in this pathway are encoded by genes belonging to three loci hin1, hin2 and hin3 and by the gene hinK. The enzymes HinABCD catalyze the transport and oxidative deamination of histamine to 4-imidazoleacetic acid (ImAA). This reaction is coupled to those of other well-known enzymatic systems (DadXAR and CoxBA-C) that ensure both the recovery of the pyruvate required for Hin deamination and the genesis of the energy needed for Hin uptake. The proteins HinGHFLKIJ catalyze the sequential transformation of ImAA to fumaric acid via N2 -formylisoasparagine, formylaspartic acid and aspartic acid. The identified Hin pathway encompasses all the genes and proteins (transporters, energizing systems, catabolic enzymes and regulators) needed for the biological degradation of Hin. Our work was facilitated by the design and isolation of genetically engineered strains that degrade Hin or ImAA and of mutants that accumulate Ala, Asp and Hin catabolites. The implications of this research with respect to potential biotechnological applications are discussed.}, } @article {pmid29614210, year = {2018}, author = {Ogonowski, M and Motiei, A and Ininbergs, K and Hell, E and Gerdes, Z and Udekwu, KI and Bacsik, Z and Gorokhova, E}, title = {Evidence for selective bacterial community structuring on microplastics.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2796-2808}, doi = {10.1111/1462-2920.14120}, pmid = {29614210}, issn = {1462-2920}, support = {942-2015-1866//The Joint Programming Initiative Healthy and Productive Seas and Oceans (JPI-Oceans) WEATHER-MIC project by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS)/ ; 216-2013-1010//The Joint Programming Initiative Healthy and Productive Seas and Oceans (JPI-Oceans) WEATHER-MIC project by the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning (FORMAS)/ ; //BONUS, the joint Baltic Sea research and development program (Art 185)/ ; 2017-00979//European Union's Seventh Program for research, technological development and demonstration and from the Sweden's Innovation Agency (VINNOVA)/ ; }, abstract = {In aquatic ecosystems, microplastics are a relatively new anthropogenic substrate that can readily be colonized by biofilm-forming organisms. To examine the effects of substrate type on microbial community assembly, we exposed ambient Baltic bacterioplankton to plastic substrates commonly found in marine environments (polyethylene, polypropylene and polystyrene) as well as native (cellulose) and inert (glass beads) particles for 2 weeks under controlled conditions. The source microbial communities and those of the biofilms were analyzed by Illumina sequencing of the 16S rRNA gene libraries. All biofilm communities displayed lower diversity and evenness compared with the source community, suggesting substrate-driven selection. Moreover, the plastics-associated communities were distinctly different from those on the non-plastic substrates. Whereas plastics hosted greater than twofold higher abundance of Burkholderiales, the non-plastic substrates had a significantly higher proportion of Actinobacteria and Cytophagia. Variation in the community structure, but not the cell abundance, across the treatments was strongly linked to the substrate hydrophobicity. Thus, microplastics host distinct bacterial communities, at least during early successional stages.}, } @article {pmid29614209, year = {2018}, author = {Guerrero-Galán, C and Delteil, A and Garcia, K and Houdinet, G and Conéjéro, G and Gaillard, I and Sentenac, H and Zimmermann, SD}, title = {Plant potassium nutrition in ectomycorrhizal symbiosis: properties and roles of the three fungal TOK potassium channels in Hebeloma cylindrosporum.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1873-1887}, doi = {10.1111/1462-2920.14122}, pmid = {29614209}, issn = {1462-2920}, abstract = {Ectomycorrhizal fungi play an essential role in the ecology of boreal and temperate forests through the improvement of tree mineral nutrition. Potassium (K+) is an essential nutrient for plants and is needed in high amounts. We recently demonstrated that the ectomycorrhizal fungus Hebeloma cylindrosporum improves the K+ nutrition of Pinus pinaster under shortage conditions. Part of the transport systems involved in K+ uptake by the fungus has been deciphered, while the molecular players responsible for the transfer of this cation towards the plant remain totally unknown. Analysis of the genome of H. cylindrosporum revealed the presence of three putative tandem-pore outward-rectifying K+ (TOK) channels that could contribute to this transfer. Here, we report the functional characterization of these three channels through two-electrode voltage-clamp experiments in oocytes and yeast complementation assays. The expression pattern and physiological role of these channels were analysed in symbiotic interaction with P. pinaster. Pine seedlings colonized by fungal transformants overexpressing two of them displayed a larger accumulation of K+ in shoots. This study revealed that TOK channels have distinctive properties and functions in axenic and symbiotic conditions and suggested that HcTOK2.2 is implicated in the symbiotic transfer of K+ from the fungus towards the plant.}, } @article {pmid29614208, year = {2018}, author = {Gilbert, JA}, title = {Ecological medicine.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14115}, pmid = {29614208}, issn = {1462-2920}, } @article {pmid29611898, year = {2018}, author = {Okubo, T and Matsushita, M and Nakamura, S and Matsuo, J and Nagai, H and Yamaguchi, H}, title = {Acanthamoeba S13WT relies on its bacterial endosymbiont to backpack human pathogenic bacteria and resist Legionella infection on solid media.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {344-354}, doi = {10.1111/1758-2229.12645}, pmid = {29611898}, issn = {1758-2229}, abstract = {Soil-borne amoeba Acanthamoeba S13WT has an endosymbiotic relationship with an environmental Neochlamydia bacterial strain. However, regardless of extensive experiments in liquid media, the biological advantage of the symbiosis remained elusive. We therefore explored the role of the endosymbiont in predator-prey interactions on solid media. A mixed culture of the symbiotic or aposymbiotic amoebae and GFP-expressing Escherichia coli or Salmonella Enteritidis was spotted onto the centre of a LB or B-CYE agar plate preinoculated with a ring of mCherry-expressing Legionella pneumophila (Legionella 'wall'). The spread of the amoebae on the plate was assessed using a fluorescence imaging system or scanning electron microscopy. As a result, in contrast to the aposymbiotic amoebae, the symbiotic amoebae backpacked these GFP-expressing bacteria and formed flower-like fluorescence patterns in an anticlockwise direction. Other bacteria (Pseudomonas aeruginosa and Stenotrophomonas maltophilia), but not Staphylococcus aureus, were also backpacked by the symbiotic amoebae on LB agar, although lacked the movement to anticlockwise direction. Furthermore, in contrast to the aposymbiotic amoebae, the symbiotic amoebae backpacking the E. coli broke through the Legionella 'wall' on B-CYE agar plates. Thus, we concluded that Acanthamoeba S13WT required the Neochlamydia endosymbiont to backpack human pathogenic bacteria and resist Legionella infection on solid agar.}, } @article {pmid29611897, year = {2018}, author = {Rodelli, D and Jovane, L and Roberts, AP and Cypriano, J and Abreu, F and Lins, U}, title = {Fingerprints of partial oxidation of biogenic magnetite from cultivated and natural marine magnetotactic bacteria using synchrotron radiation.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {337-343}, doi = {10.1111/1758-2229.12644}, pmid = {29611897}, issn = {1758-2229}, abstract = {Magnetotactic bacteria are a multi-phyletic group of bacteria that synthesize membrane-bound magnetic minerals. Understanding the preservation of these minerals in various environments (e.g., with varying oxygen concentrations and iron supply) is important for understanding their role as carriers of primary magnetizations in sediments and sedimentary rocks. Here we present X-ray near edge structure (XANES) spectra for Fe in magnetotactic bacteria samples from recent sediments to assess surface oxidation and crystal structure changes in bacterial magnetite during early burial. Our results are compared with a XANES spectrum of cultivated Magnetofaba australis samples, and with magnetic properties, and indicate that oxidation of magnetite to maghemite increases with depth in the sediment due to longer exposure to molecular oxygen. These results are relevant to understanding magnetic signatures carried by magnetofossils in oxic sediments and sedimentary rocks of different ages.}, } @article {pmid29611894, year = {2018}, author = {Fernández-Cabezón, L and Galán, B and García, JL}, title = {Unravelling a new catabolic pathway of C-19 steroids in Mycobacterium smegmatis.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1815-1827}, doi = {10.1111/1462-2920.14114}, pmid = {29611894}, issn = {1462-2920}, abstract = {In this work, we have characterized the C-19+ gene cluster (MSMEG_2851 to MSMEG_2901) of Mycobacterium smegmatis. By in silico analysis, we have identified the genes encoding enzymes involved in the modification of the A/B steroid rings during the catabolism of C-19 steroids in certain M. smegmatis mutants mapped in the PadR-like regulator (MSMEG_2868), that constitutively express the C-19+ gene cluster. By using gene complementation assays, resting-cell biotransformations and deletion mutants, we have characterized the most critical genes of the cluster, that is, kstD2, kstD3, kshA2, kshB2, hsaA2, hsaC2 and hsaD2. These results have allowed us to propose a new catabolic route named C-19+ pathway for the mineralization of C-19 steroids in M. smegmatis. Our data suggest that the deletion of the C-19+ gene cluster may be useful to engineer more robust and efficient M. smegmatis strains to produce C-19 steroids from sterols. Moreover, the new KshA2, KshB2, KstD2 and KstD3 isoenzymes may be useful to design new microbial cell factories for the 9α-hydroxylation and/or Δ1-dehydrogenation of 3-ketosteroids.}, } @article {pmid29611893, year = {2018}, author = {Sedano-Núñez, VT and Boeren, S and Stams, AJM and Plugge, CM}, title = {Comparative proteome analysis of propionate degradation by Syntrophobacter fumaroxidans in pure culture and in coculture with methanogens.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1842-1856}, pmid = {29611893}, issn = {1462-2920}, support = {323009//European Research Council/International ; }, abstract = {Syntrophobacter fumaroxidans is a sulfate-reducing bacterium able to grow on propionate axenically or in syntrophic interaction with methanogens or other sulfate-reducing bacteria. We performed a proteome analysis of S. fumaroxidans growing with propionate axenically with sulfate or fumarate, and in syntrophy with Methanospirillum hungatei, Methanobacterium formicicum or Desulfovibrio desulfuricans. Special attention was put on the role of hydrogen and formate in interspecies electron transfer (IET) and energy conservation. Formate dehydrogenase Fdh1 and hydrogenase Hox were the main confurcating enzymes used for energy conservation. In the periplasm, Fdh2 and hydrogenase Hyn play an important role in reverse electron transport associated with succinate oxidation. Periplasmic Fdh3 and Fdh5 were involved in IET. The sulfate reduction pathway was poorly regulated and many enzymes associated with sulfate reduction (Sat, HppA, AprAB, DsrAB and DsrC) were abundant even at conditions where sulfate was not present. Proteins similar to heterodisulfide reductases (Hdr) were abundant. Hdr/Flox was detected in all conditions while HdrABC/HdrL was exclusively detected when sulfate was available; these complexes most likely confurcate electrons. Our results suggest that S. fumaroxidans mainly used formate for electron release and that different confurcating mechanisms were used in its sulfidogenic metabolism.}, } @article {pmid29611803, year = {2018}, author = {Peintner, U and Knapp, M and Fleischer, V and Walch, G and Dresch, P}, title = {Corrigendum: Myrmecridium hiemale sp. nov. from snow-covered alpine soil is the first eurypsychrophile in this genus of anamorphic fungi.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1408}, doi = {10.1099/ijsem.0.002696}, pmid = {29611803}, issn = {1466-5034}, } @article {pmid29611802, year = {2018}, author = {Wu, YH and Yan, J and Fang, C and Huo, YY and Ma, WL and Zhang, DM and Wang, CS and Xu, XW}, title = {Gracilimonas amylolytica sp. nov., isolated from deep-sea sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1713-1718}, doi = {10.1099/ijsem.0.002734}, pmid = {29611802}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Gram-Negative Aerobic Rods and Cocci/*classification/genetics/isolation & purification ; Pacific Ocean ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterium, designated LA399T, was isolated from deep-sea sediment collected from the Pacific Ocean. Cells of strain LA399T grew in the medium containing 0-10.0 % of NaCl (w/v; optimum 3.0-5.0 %), pH 6.5-8.0 (optimum 7.0) and 20-40 °C (optimum 37 °C). Aesculin, gelatin, starch and Tween 80 were hydrolysed. Strain LA399T was closely related to Gracilimonas halophila WDS2C40T (97.0 % sequence similarity), Gracilimonas mengyeensis YIM J14T (96.4 %), Gracilimonas rosea CL-KR2T (96.4 %) and Gracilimonas tropica DSM 19535T (96.0 %), and exhibited equal or less than 96.0 % sequence similarity to other type strains of species with validly published names. Phylogenetic analyses revealed that strain LA399T clustered with the clade comprising the Gracilimonas species and formed an independent lineage. Strain LA399T contained menaquinone 7 as the sole isoprenoid quinone and iso-C15 : 0, anteiso-C15 : 0, summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) and summed feature 9 (iso-C17 : 1ω9c/10-methyl C16 : 0) as the predominant cellular fatty acids. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid and three unidentified glycolipids. The DNA G+C content was 45.3 mol%. According to the phylogenetic, chemotaxonomic and phenotypic data, it represents a novel species of the genus Gracilimonas, for which the name Gracilimonas amylolytica is proposed. The type strain is LA399T (=CGMCC 1.16248T=KCTC 52885T).}, } @article {pmid29611798, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 68, part 1, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {979-981}, doi = {10.1099/ijsem.0.002597}, pmid = {29611798}, issn = {1466-5034}, } @article {pmid29611630, year = {2018}, author = {Yu, X and Zhong, MJ and Li, DY and Jin, L and Liao, WB and Kotrschal, A}, title = {Large-brained frogs mature later and live longer.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1174-1183}, doi = {10.1111/evo.13478}, pmid = {29611630}, issn = {1558-5646}, abstract = {Brain sizes vary substantially across vertebrate taxa, yet, the evolution of brain size appears tightly linked to the evolution of life histories. For example, larger brained species generally live longer than smaller brained species. A larger brain requires more time to grow and develop at a cost of exceeded gestation period and delayed weaning age. The cost of slower development may be compensated by better homeostasis control and increased cognitive abilities, both of which should increase survival probabilities and hence life span. To date, this relationship between life span and brain size seems well established in homoeothermic animals, especially in mammals. Whether this pattern occurs also in other clades of vertebrates remains enigmatic. Here, we undertake the first comparative test of the relationship between life span and brain size in an ectothermic vertebrate group, the anuran amphibians. After controlling for the effects of shared ancestry and body size, we find a positive correlation between brain size, age at sexual maturation, and life span across 40 species of frogs. Moreover, we also find that the ventral brain regions, including the olfactory bulbs, are larger in long-lived species. Our results indicate that the relationship between life history and brain evolution follows a general pattern across vertebrate clades.}, } @article {pmid29611186, year = {2018}, author = {O'Brien, S and Hesse, E and Luján, A and Hodgson, DJ and Gardner, A and Buckling, A}, title = {No effect of intraspecific relatedness on public goods cooperation in a complex community.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1165-1173}, pmid = {29611186}, issn = {1558-5646}, abstract = {Many organisms-notably microbes-are embedded within complex communities where cooperative behaviors in the form of excreted public goods can benefit other species. Under such circumstances, intraspecific interactions are likely to be less important in driving the evolution of cooperation. We first illustrate this idea with a simple theoretical model, showing that relatedness-the extent to which individuals with the same cooperative alleles interact with each other-has a reduced impact on the evolution of cooperation when public goods are shared between species. We test this empirically using strain of Pseudomonas aeruginosa that vary in their production of metal-chelating siderophores in copper contaminated compost (an interspecific public good). We show that nonsiderophore producers grow poorly relative to producers under high relatedness, but this cost can be alleviated by the presence of the isogenic producer (low relatedness) and/or the compost microbial community. Hence, relatedness can become unimportant when public goods provide interspecific benefits.}, } @article {pmid29610942, year = {2018}, author = {Yadav, S and Kumar, A and Gupta, M and Maitra, SS}, title = {Cross-Reactivity of Prokaryotic 16S rDNA-Specific Primers to Eukaryotic DNA: Mistaken Microbial Community Profiling in Environmental Samples.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1038-1045}, pmid = {29610942}, issn = {1432-0991}, support = {PURSE//Department of Science and Technology, GOI/ ; }, mesh = {Animals ; Bacteria/*classification/*genetics/isolation & purification ; Cattle ; DNA Primers/*genetics ; DNA Restriction Enzymes/metabolism ; DNA, Chloroplast/genetics ; DNA, Mitochondrial/genetics ; DNA, Ribosomal/genetics ; Denaturing Gradient Gel Electrophoresis ; Eukaryota/*genetics ; Feces/microbiology ; Fungi/*classification/*genetics/isolation & purification ; Gene Expression Profiling ; Polymerase Chain Reaction ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {16S ribosomal RNA gene sequences are characteristically used as gold-standard genetic marker for the determination of bacterial and/or archaeal biodiversity, and community profiling of environmental samples. The 16S rRNA amplicon analysis till-date is taken as a standard method for investigation and identification of uncultivable bacteria in microbial diversity studies. The accuracy of these analyses strongly depends upon the choice of primers. It is presumed that these primers do not participate in non-specific amplifications. In the present study, by in silico, PCR and denaturing gradient gel electrophoresis (DGGE) analysis, we have shown that primers do cross-react with eukaryotic DNAs as well, eventually leading to overestimation of microbial biodiversity. We further demonstrated that the overestimation is not only due to cross-reaction with eukaryotic mitochondrial or plastid DNA, but also with eukaryotic chromosomal DNA, that is ubiquitous in environmental samples. We tried to establish methanogenic diversity in municipal solid waste (MSW) leachates and cow dung samples before and after enrichment of the prokaryotic DNA from eukaryotic ones. Results revealed that bands disappeared/get lightened in bacterial 16S rRNA-based DGGE community profiles, after prokaryotic DNA enrichment, but not in mcrA-based community profiles.}, } @article {pmid29610517, year = {2018}, author = {Leth, ML and Ejby, M and Workman, C and Ewald, DA and Pedersen, SS and Sternberg, C and Bahl, MI and Licht, TR and Aachmann, FL and Westereng, B and Abou Hachem, M}, title = {Differential bacterial capture and transport preferences facilitate co-growth on dietary xylan in the human gut.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {570-580}, doi = {10.1038/s41564-018-0132-8}, pmid = {29610517}, issn = {2058-5276}, abstract = {Metabolism of dietary glycans is pivotal in shaping the human gut microbiota. However, the mechanisms that promote competition for glycans among gut commensals remain unclear. Roseburia intestinalis, an abundant butyrate-producing Firmicute, is a key degrader of the major dietary fibre xylan. Despite the association of this taxon to a healthy microbiota, insight is lacking into its glycan utilization machinery. Here, we investigate the apparatus that confers R. intestinalis growth on different xylans. R. intestinalis displays a large cell-attached modular xylanase that promotes multivalent and dynamic association to xylan via four xylan-binding modules. This xylanase operates in concert with an ATP-binding cassette transporter to mediate breakdown and selective internalization of xylan fragments. The transport protein of R. intestinalis prefers oligomers of 4-5 xylosyl units, whereas the counterpart from a model xylan-degrading Bacteroides commensal targets larger ligands. Although R. intestinalis and the Bacteroides competitor co-grew in a mixed culture on xylan, R. intestinalis dominated on the preferred transport substrate xylotetraose. These findings highlight the differentiation of capture and transport preferences as a possible strategy to facilitate co-growth on abundant dietary fibres and may offer a unique route to manipulate the microbiota based on glycan transport preferences in therapeutic interventions to boost distinct taxa.}, } @article {pmid29610481, year = {2018}, author = {Zhang, W and Bojorquez-Gomez, A and Velez, DO and Xu, G and Sanchez, KS and Shen, JP and Chen, K and Licon, K and Melton, C and Olson, KM and Yu, MK and Huang, JK and Carter, H and Farley, EK and Snyder, M and Fraley, SI and Kreisberg, JF and Ideker, T}, title = {A global transcriptional network connecting noncoding mutations to changes in tumor gene expression.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {613-620}, pmid = {29610481}, issn = {1546-1718}, support = {P41 GM103504/GM/NIGMS NIH HHS/United States ; UL1 TR001442/TR/NCATS NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 HG009979/HG/NHGRI NIH HHS/United States ; U54 CA209891/CA/NCI NIH HHS/United States ; DP5 OD017937/OD/NIH HHS/United States ; P50 GM085764/GM/NIGMS NIH HHS/United States ; U24 CA184427/CA/NCI NIH HHS/United States ; }, abstract = {Although cancer genomes are replete with noncoding mutations, the effects of these mutations remain poorly characterized. Here we perform an integrative analysis of 930 tumor whole genomes and matched transcriptomes, identifying a network of 193 noncoding loci in which mutations disrupt target gene expression. These 'somatic eQTLs' (expression quantitative trait loci) are frequently mutated in specific cancer tissues, and the majority can be validated in an independent cohort of 3,382 tumors. Among these, we find that the effects of noncoding mutations on DAAM1, MTG2 and HYI transcription are recapitulated in multiple cancer cell lines and that increasing DAAM1 expression leads to invasive cell migration. Collectively, the noncoding loci converge on a set of core pathways, permitting a classification of tumors into pathway-based subtypes. The somatic eQTL network is disrupted in 88% of tumors, suggesting widespread impact of noncoding mutations in cancer.}, } @article {pmid29610480, year = {2018}, author = {Zhou, W and Dinh, HQ and Ramjan, Z and Weisenberger, DJ and Nicolet, CM and Shen, H and Laird, PW and Berman, BP}, title = {DNA methylation loss in late-replicating domains is linked to mitotic cell division.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {591-602}, pmid = {29610480}, issn = {1546-1718}, support = {U24 CA143882/CA/NCI NIH HHS/United States ; R01 CA170550/CA/NCI NIH HHS/United States ; R01 HG006705/HG/NHGRI NIH HHS/United States ; U24 CA210969/CA/NCI NIH HHS/United States ; U01 CA184826/CA/NCI NIH HHS/United States ; }, abstract = {DNA methylation loss occurs frequently in cancer genomes, primarily within lamina-associated, late-replicating regions termed partially methylated domains (PMDs). We profiled 39 diverse primary tumors and 8 matched adjacent tissues using whole-genome bisulfite sequencing (WGBS) and analyzed them alongside 343 additional human and 206 mouse WGBS datasets. We identified a local CpG sequence context associated with preferential hypomethylation in PMDs. Analysis of CpGs in this context ('solo-WCGWs') identified previously undetected PMD hypomethylation in almost all healthy tissue types. PMD hypomethylation increased with age, beginning during fetal development, and appeared to track the accumulation of cell divisions. In cancer, PMD hypomethylation depth correlated with somatic mutation density and cell cycle gene expression, consistent with its reflection of mitotic history and suggesting its application as a mitotic clock. We propose that late replication leads to lifelong progressive methylation loss, which acts as a biomarker for cellular aging and which may contribute to oncogenesis.}, } @article {pmid29610479, year = {2018}, author = {van der Wijst, MGP and Brugge, H and de Vries, DH and Deelen, P and Swertz, MA and , and , and Franke, L}, title = {Single-cell RNA sequencing identifies celltype-specific cis-eQTLs and co-expression QTLs.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {493-497}, pmid = {29610479}, issn = {1546-1718}, abstract = {Genome-wide association studies have identified thousands of genetic variants that are associated with disease 1 . Most of these variants have small effect sizes, but their downstream expression effects, so-called expression quantitative trait loci (eQTLs), are often large 2 and celltype-specific3-5. To identify these celltype-specific eQTLs using an unbiased approach, we used single-cell RNA sequencing to generate expression profiles of ~25,000 peripheral blood mononuclear cells from 45 donors. We identified previously reported cis-eQTLs, but also identified new celltype-specific cis-eQTLs. Finally, we generated personalized co-expression networks and identified genetic variants that significantly alter co-expression relationships (which we termed 'co-expression QTLs'). Single-cell eQTL analysis thus allows for the identification of genetic variants that impact regulatory networks.}, } @article {pmid29610478, year = {2018}, author = {Martyn, GE and Wienert, B and Yang, L and Shah, M and Norton, LJ and Burdach, J and Kurita, R and Nakamura, Y and Pearson, RCM and Funnell, APW and Quinlan, KGR and Crossley, M}, title = {Natural regulatory mutations elevate the fetal globin gene via disruption of BCL11A or ZBTB7A binding.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {498-503}, doi = {10.1038/s41588-018-0085-0}, pmid = {29610478}, issn = {1546-1718}, abstract = {β-hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia result from mutations in the adult HBB (β-globin) gene. Reactivating the developmentally silenced fetal HBG1 and HBG2 (γ-globin) genes is a therapeutic goal for treating SCD and β-thalassemia 1 . Some forms of hereditary persistence of fetal hemoglobin (HPFH), a rare benign condition in which individuals express the γ-globin gene throughout adulthood, are caused by point mutations in the γ-globin gene promoter at regions residing ~115 and 200 bp upstream of the transcription start site. We found that the major fetal globin gene repressors BCL11A and ZBTB7A (also known as LRF) directly bound to the sites at -115 and -200 bp, respectively. Furthermore, introduction of naturally occurring HPFH-associated mutations into erythroid cells by CRISPR-Cas9 disrupted repressor binding and raised γ-globin gene expression. These findings clarify how these HPFH-associated mutations operate and demonstrate that BCL11A and ZBTB7A are major direct repressors of the fetal globin gene.}, } @article {pmid29610477, year = {2018}, author = {Wang, X and Thein, SL}, title = {Switching from fetal to adult hemoglobin.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {478-480}, doi = {10.1038/s41588-018-0094-z}, pmid = {29610477}, issn = {1546-1718}, } @article {pmid29610476, year = {2018}, author = {Rogers, ZN and McFarland, CD and Winters, IP and Seoane, JA and Brady, JJ and Yoon, S and Curtis, C and Petrov, DA and Winslow, MM}, title = {Mapping the in vivo fitness landscape of lung adenocarcinoma tumor suppression in mice.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {483-486}, pmid = {29610476}, issn = {1546-1718}, support = {R25 CA180993/CA/NCI NIH HHS/United States ; F32 CA189659/CA/NCI NIH HHS/United States ; R01 CA175336/CA/NCI NIH HHS/United States ; R01 CA207133/CA/NCI NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; F31 CA210627/CA/NCI NIH HHS/United States ; R35 GM118165/GM/NIGMS NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; }, abstract = {The functional impact of most genomic alterations found in cancer, alone or in combination, remains largely unknown. Here we integrate tumor barcoding, CRISPR/Cas9-mediated genome editing and ultra-deep barcode sequencing to interrogate pairwise combinations of tumor suppressor alterations in autochthonous mouse models of human lung adenocarcinoma. We map the tumor suppressive effects of 31 common lung adenocarcinoma genotypes and identify a landscape of context dependence and differential effect strengths.}, } @article {pmid29610475, year = {2018}, author = {Armenia, J and Wankowicz, SAM and Liu, D and Gao, J and Kundra, R and Reznik, E and Chatila, WK and Chakravarty, D and Han, GC and Coleman, I and Montgomery, B and Pritchard, C and Morrissey, C and Barbieri, CE and Beltran, H and Sboner, A and Zafeiriou, Z and Miranda, S and Bielski, CM and Penson, AV and Tolonen, C and Huang, FW and Robinson, D and Wu, YM and Lonigro, R and Garraway, LA and Demichelis, F and Kantoff, PW and Taplin, ME and Abida, W and Taylor, BS and Scher, HI and Nelson, PS and de Bono, JS and Rubin, MA and Sawyers, CL and Chinnaiyan, AM and , and Schultz, N and Van Allen, EM and , }, title = {The long tail of oncogenic drivers in prostate cancer.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {645-651}, pmid = {29610475}, issn = {1546-1718}, support = {R01 CA193837/CA/NCI NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; K08 CA188615/CA/NCI NIH HHS/United States ; P50 CA092629/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA155169/CA/NCI NIH HHS/United States ; }, abstract = {Comprehensive genomic characterization of prostate cancer has identified recurrent alterations in genes involved in androgen signaling, DNA repair, and PI3K signaling, among others. However, larger and uniform genomic analysis may identify additional recurrently mutated genes at lower frequencies. Here we aggregate and uniformly analyze exome sequencing data from 1,013 prostate cancers. We identify and validate a new class of E26 transformation-specific (ETS)-fusion-negative tumors defined by mutations in epigenetic regulators, as well as alterations in pathways not previously implicated in prostate cancer, such as the spliceosome pathway. We find that the incidence of significantly mutated genes (SMGs) follows a long-tail distribution, with many genes mutated in less than 3% of cases. We identify a total of 97 SMGs, including 70 not previously implicated in prostate cancer, such as the ubiquitin ligase CUL3 and the transcription factor SPEN. Finally, comparing primary and metastatic prostate cancer identifies a set of genomic markers that may inform risk stratification.}, } @article {pmid29610472, year = {2018}, author = {Estes, L and Elsen, PR and Treuer, T and Ahmed, L and Caylor, K and Chang, J and Choi, JJ and Ellis, EC}, title = {The spatial and temporal domains of modern ecology.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {819-826}, doi = {10.1038/s41559-018-0524-4}, pmid = {29610472}, issn = {2397-334X}, abstract = {To understand ecological phenomena, it is necessary to observe their behaviour across multiple spatial and temporal scales. Since this need was first highlighted in the 1980s, technology has opened previously inaccessible scales to observation. To help to determine whether there have been corresponding changes in the scales observed by modern ecologists, we analysed the resolution, extent, interval and duration of observations (excluding experiments) in 348 studies that have been published between 2004 and 2014. We found that observational scales were generally narrow, because ecologists still primarily use conventional field techniques. In the spatial domain, most observations had resolutions ≤1 m2 and extents ≤10,000 ha. In the temporal domain, most observations were either unreplicated or infrequently repeated (>1 month interval) and ≤1 year in duration. Compared with studies conducted before 2004, observational durations and resolutions appear largely unchanged, but intervals have become finer and extents larger. We also found a large gulf between the scales at which phenomena are actually observed and the scales those observations ostensibly represent, raising concerns about observational comprehensiveness. Furthermore, most studies did not clearly report scale, suggesting that it remains a minor concern. Ecologists can better understand the scales represented by observations by incorporating autocorrelation measures, while journals can promote attentiveness to scale by implementing scale-reporting standards.}, } @article {pmid29610471, year = {2018}, author = {Davín, AA and Tannier, E and Williams, TA and Boussau, B and Daubin, V and Szöllősi, GJ}, title = {Gene transfers can date the tree of life.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {904-909}, pmid = {29610471}, issn = {2397-334X}, support = {714774//European Research Council/International ; }, abstract = {Biodiversity has always been predominantly microbial, and the scarcity of fossils from bacteria, archaea and microbial eukaryotes has prevented a comprehensive dating of the tree of life. Here, we show that patterns of lateral gene transfer deduced from an analysis of modern genomes encode a novel and abundant source of information about the temporal coexistence of lineages throughout the history of life. We use state-of-the-art species tree-aware phylogenetic methods to reconstruct the history of thousands of gene families and demonstrate that dates implied by gene transfers are consistent with estimates from relaxed molecular clocks in Bacteria, Archaea and Eukarya. We present the order of speciations according to lateral gene transfer data calibrated to geological time for three datasets comprising 40 genomes for Cyanobacteria, 60 genomes for Archaea and 60 genomes for Fungi. An inspection of discrepancies between transfers and clocks and a comparison with mammalian fossils show that gene transfer in microbes is potentially as informative for dating the tree of life as the geological record in macroorganisms.}, } @article {pmid29610470, year = {2018}, author = {Dos Reis, M}, title = {Fossil-free dating.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {771-772}, doi = {10.1038/s41559-018-0532-4}, pmid = {29610470}, issn = {2397-334X}, } @article {pmid29610469, year = {2018}, author = {Ernest, SKM}, title = {Scales of data.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {769-770}, doi = {10.1038/s41559-018-0523-5}, pmid = {29610469}, issn = {2397-334X}, } @article {pmid29610468, year = {2018}, author = {Pascual-Anaya, J and Sato, I and Sugahara, F and Higuchi, S and Paps, J and Ren, Y and Takagi, W and Ruiz-Villalba, A and Ota, KG and Wang, W and Kuratani, S}, title = {Hagfish and lamprey Hox genes reveal conservation of temporal colinearity in vertebrates.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {859-866}, doi = {10.1038/s41559-018-0526-2}, pmid = {29610468}, issn = {2397-334X}, abstract = {Hox genes exert fundamental roles for proper regional specification along the main rostro-caudal axis of animal embryos. They are generally expressed in restricted spatial domains according to their position in the cluster (spatial colinearity)-a feature that is conserved across bilaterians. In jawed vertebrates (gnathostomes), the position in the cluster also determines the onset of expression of Hox genes (a feature known as whole-cluster temporal colinearity (WTC)), while in invertebrates this phenomenon is displayed as a subcluster-level temporal colinearity. However, little is known about the expression profile of Hox genes in jawless vertebrates (cyclostomes); therefore, the evolutionary origin of WTC, as seen in gnathostomes, remains a mystery. Here, we show that Hox genes in cyclostomes are expressed according to WTC during development. We investigated the Hox repertoire and Hox gene expression profiles in three different species-a hagfish, a lamprey and a shark-encompassing the two major groups of vertebrates, and found that these are expressed following a whole-cluster, temporally staggered pattern, indicating that WTC has been conserved during the past 500 million years despite drastically different genome evolution and morphological outputs between jawless and jawed vertebrates.}, } @article {pmid29610467, year = {2018}, author = {Photopoulou, T}, title = {Human footprint restricts ranges.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {773-774}, doi = {10.1038/s41559-018-0538-y}, pmid = {29610467}, issn = {2397-334X}, } @article {pmid29610466, year = {2018}, author = {Wolfe, JM and Fournier, GP}, title = {Horizontal gene transfer constrains the timing of methanogen evolution.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {897-903}, doi = {10.1038/s41559-018-0513-7}, pmid = {29610466}, issn = {2397-334X}, abstract = {Microbial methanogenesis may have been a major component of Earth's carbon cycle during the Archaean eon, generating a methane greenhouse that increased global temperatures enough for a liquid hydrosphere, despite the Sun's lower luminosity at the time. Evaluation of potential solutions to the 'faint young Sun' hypothesis by determining the age of microbial methanogenesis has been limited by ambiguous geochemical evidence and the absence of a diagnostic fossil record. To overcome these challenges, we use a temporal constraint: a horizontal gene transfer event from within archaeal methanogens to the ancestor of Cyanobacteria, one of the few microbial clades with recognized crown-group fossils. Results of molecular clock analyses calibrated by this horizontal-gene-transfer-propagated constraint show methanogens diverging within Euryarchaeota no later than 3.51 billion years ago, with methanogenesis itself probably evolving earlier. This timing provides independent support for scenarios wherein microbial methane production was important in maintaining temperatures on the early Earth.}, } @article {pmid29610398, year = {2018}, author = {Jacob, JT and Coulombe, PA and Kwan, R and Omary, MB}, title = {Types I and II Keratin Intermediate Filaments.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, pmid = {29610398}, issn = {1943-0264}, support = {R01 AR042047/AR/NIAMS NIH HHS/United States ; R01 AR044232/AR/NIAMS NIH HHS/United States ; R01 CA160255/CA/NCI NIH HHS/United States ; T32 CA009110/CA/NCI NIH HHS/United States ; }, abstract = {SummaryKeratins-types I and II-are the intermediate-filament-forming proteins expressed in epithelial cells. They are encoded by 54 evolutionarily conserved genes (28 type I, 26 type II) and regulated in a pairwise and tissue type-, differentiation-, and context-dependent manner. Here, we review how keratins serve multiple homeostatic and stress-triggered mechanical and nonmechanical functions, including maintenance of cellular integrity, regulation of cell growth and migration, and protection from apoptosis. These functions are tightly regulated by posttranslational modifications and keratin-associated proteins. Genetically determined alterations in keratin-coding sequences underlie highly penetrant and rare disorders whose pathophysiology reflects cell fragility or altered tissue homeostasis. Furthermore, keratin mutation or misregulation represents risk factors or genetic modifiers for several additional acute and chronic diseases.}, } @article {pmid29610356, year = {2018}, author = {Mooshagian, E and Snyder, LH}, title = {Spatial eye-hand coordination during bimanual reaching is not systematically coded in either LIP or PRR.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3817-E3826}, pmid = {29610356}, issn = {1091-6490}, support = {F32 NS076206/NS/NINDS NIH HHS/United States ; R01 EY012135/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Arm/*physiology ; Brain Mapping ; Macaca mulatta ; Male ; Nerve Net ; Parietal Lobe/*physiology ; Psychomotor Performance ; Saccades ; }, abstract = {We often orient to where we are about to reach. Spatial and temporal correlations in eye and arm movements may depend on the posterior parietal cortex (PPC). Spatial representations of saccade and reach goals preferentially activate cells in the lateral intraparietal area (LIP) and the parietal reach region (PRR), respectively. With unimanual reaches, eye and arm movement patterns are highly stereotyped. This makes it difficult to study the neural circuits involved in coordination. Here, we employ bimanual reaching to two different targets. Animals naturally make a saccade first to one target and then the other, resulting in different patterns of limb-gaze coordination on different trials. Remarkably, neither LIP nor PRR cells code which target the eyes will move to first. These results suggest that the parietal cortex plays at best only a permissive role in some aspects of eye-hand coordination and makes the role of LIP in saccade generation unclear.}, } @article {pmid29610355, year = {2018}, author = {Konova, AB and Louie, K and Glimcher, PW}, title = {The computational form of craving is a selective multiplication of economic value.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4122-4127}, pmid = {29610355}, issn = {1091-6490}, support = {F32 DA039648/DA/NIDA NIH HHS/United States ; R01 DA038063/DA/NIDA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Algorithms ; Beverages/economics ; Candy/economics ; Choice Behavior ; *Costs and Cost Analysis ; *Craving ; Cues ; Fasting/psychology ; Feeding Behavior/*psychology ; Female ; Food Preferences/psychology ; Humans ; Male ; Mental Recall ; Middle Aged ; Models, Economic ; *Models, Psychological ; Odorants ; Photic Stimulation ; Snacks/*psychology ; Time Factors ; Young Adult ; }, abstract = {Craving is thought to be a specific desire state that biases choice toward the desired object, be it chocolate or drugs. A vast majority of people report having experienced craving of some kind. In its pathological form craving contributes to health outcomes in addiction and obesity. Yet despite its ubiquity and clinical relevance we still lack a basic neurocomputational understanding of craving. Here, using an instantaneous measure of subjective valuation and selective cue exposure, we identify a behavioral signature of a food craving-like state and advance a computational framework for understanding how this state might transform valuation to bias choice. We find desire induced by exposure to a specific high-calorie, high-fat/sugar snack good is expressed in subjects' momentary willingness to pay for this good. This effect is selective but not exclusive to the exposed good; rather, we find it generalizes to nonexposed goods in proportion to their subjective attribute similarity to the exposed ones. A second manipulation of reward size (number of snack units available for purchase) further suggested that a multiplicative gain mechanism supports the transformation of valuation during laboratory craving. These findings help explain how real-world food craving can result in behaviors inconsistent with preferences expressed in the absence of craving and open a path for the computational modeling of craving-like phenomena using a simple and repeatable experimental tool for assessing subjective states in economic terms.}, } @article {pmid29610354, year = {2018}, author = {Xu, WJ and Wen, H and Kim, HS and Ko, YJ and Dong, SM and Park, IS and Yook, JI and Park, S}, title = {Observation of acetyl phosphate formation in mammalian mitochondria using real-time in-organelle NMR metabolomics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4152-4157}, pmid = {29610354}, issn = {1091-6490}, mesh = {Acrylates/pharmacology ; Computer Systems ; Gene Knockout Techniques ; Genes, p53 ; HCT116 Cells ; Humans ; Metabolomics/*methods ; Mitochondria/*metabolism ; Nuclear Magnetic Resonance, Biomolecular/*methods ; Organophosphates/*metabolism ; Oxidative Phosphorylation ; Pyruvate Dehydrogenase Complex/antagonists & inhibitors/metabolism ; Tumor Suppressor Protein p53/deficiency/*physiology ; }, abstract = {Recent studies point out the link between altered mitochondrial metabolism and cancer, and detailed understanding of mitochondrial metabolism requires real-time detection of its metabolites. Employing heteronuclear 2D NMR spectroscopy and 13C3-pyruvate, we propose in-organelle metabolomics that allows for the monitoring of mitochondrial metabolic changes in real time. The approach identified acetyl phosphate from human mitochondria, whose production has been largely neglected in eukaryotic metabolism since its first description about 70 years ago in bacteria. The kinetic profile of acetyl phosphate formation was biphasic, and its transient nature suggested its role as a metabolic intermediate. The method also allowed for the estimation of pyruvate dehydrogenase (PDH) enzyme activity through monitoring of the acetyl-CoA formation, independent of competing cytosolic metabolism. The results confirmed the positive regulation of mitochondrial PDH activity by p53, a well-known tumor suppressor. Our approach can easily be applied to other organelle-specific metabolic studies.}, } @article {pmid29610353, year = {2018}, author = {Grant, MJ and Loftus, MS and Stoja, AP and Kedes, DH and Smith, MM}, title = {Superresolution microscopy reveals structural mechanisms driving the nanoarchitecture of a viral chromatin tether.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {4992-4997}, pmid = {29610353}, issn = {1091-6490}, support = {RC1 GM091175/GM/NIGMS NIH HHS/United States ; P30 CA044579/CA/NCI NIH HHS/United States ; T32 GM008136/GM/NIGMS NIH HHS/United States ; R01 DE022291/DE/NIDCR NIH HHS/United States ; R01 GM116994/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antigens, Viral/*metabolism ; COS Cells ; Cercopithecus aethiops ; Chromatin/*metabolism/ultrastructure ; *Epigenesis, Genetic ; Herpesvirus 8, Human/*metabolism ; *Imaging, Three-Dimensional ; Microscopy, Fluorescence/methods ; Nuclear Proteins/*metabolism ; }, abstract = {By tethering their circular genomes (episomes) to host chromatin, DNA tumor viruses ensure retention and segregation of their genetic material during cell divisions. Despite functional genetic and crystallographic studies, there is little information addressing the 3D structure of these tethers in cells, issues critical for understanding persistent infection by these viruses. Here, we have applied direct stochastic optical reconstruction microscopy (dSTORM) to establish the nanoarchitecture of tethers within cells latently infected with the oncogenic human pathogen, Kaposi's sarcoma-associated herpesvirus (KSHV). Each KSHV tether comprises a series of homodimers of the latency-associated nuclear antigen (LANA) that bind with their C termini to the tandem array of episomal terminal repeats (TRs) and with their N termini to host chromatin. Superresolution imaging revealed that individual KSHV tethers possess similar overall dimensions and, in aggregate, fold to occupy the volume of a prolate ellipsoid. Using plasmids with increasing numbers of TRs, we found that tethers display polymer power law scaling behavior with a scaling exponent characteristic of active chromatin. For plasmids containing a two-TR tether, we determined the size, separation, and relative orientation of two distinct clusters of bound LANA, each corresponding to a single TR. From these data, we have generated a 3D model of the episomal half of the tether that integrates and extends previously established findings from epifluorescent, crystallographic, and epigenetic approaches. Our findings also validate the use of dSTORM in establishing novel structural insights into the physical basis of molecular connections linking host and pathogen genomes.}, } @article {pmid29610352, year = {2018}, author = {Bayas, CA and Wang, J and Lee, MK and Schrader, JM and Shapiro, L and Moerner, WE}, title = {Spatial organization and dynamics of RNase E and ribosomes in Caulobacter crescentus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3712-E3721}, pmid = {29610352}, issn = {1091-6490}, support = {F32 GM100732/GM/NIGMS NIH HHS/United States ; R01 GM086196/GM/NIGMS NIH HHS/United States ; R35 GM118067/GM/NIGMS NIH HHS/United States ; R35 GM118071/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/analysis/*metabolism ; Caulobacter crescentus/*enzymology/metabolism/ultrastructure ; Cell Cycle ; Cell Polarity ; Chromosomes, Bacterial/genetics/ultrastructure ; Endoribonucleases/analysis/*metabolism ; Gene Expression Regulation, Bacterial ; Luminescent Proteins/analysis ; Microscopy, Fluorescence/methods ; Multienzyme Complexes/metabolism ; Polyribonucleotide Nucleotidyltransferase/metabolism ; RNA Helicases/metabolism ; RNA, Bacterial/biosynthesis/genetics ; RNA, Ribosomal/biosynthesis/genetics ; Ribosomes/metabolism ; Single Molecule Imaging/methods ; Subcellular Fractions/enzymology ; Templates, Genetic ; Transcription, Genetic ; }, abstract = {We report the dynamic spatial organization of Caulobacter crescentus RNase E (RNA degradosome) and ribosomal protein L1 (ribosome) using 3D single-particle tracking and superresolution microscopy. RNase E formed clusters along the central axis of the cell, while weak clusters of ribosomal protein L1 were deployed throughout the cytoplasm. These results contrast with RNase E and ribosome distribution in Escherichia coli, where RNase E colocalizes with the cytoplasmic membrane and ribosomes accumulate in polar nucleoid-free zones. For both RNase E and ribosomes in Caulobacter, we observed a decrease in confinement and clustering upon transcription inhibition and subsequent depletion of nascent RNA, suggesting that RNA substrate availability for processing, degradation, and translation facilitates confinement and clustering. Importantly, RNase E cluster positions correlated with the subcellular location of chromosomal loci of two highly transcribed rRNA genes, suggesting that RNase E's function in rRNA processing occurs at the site of rRNA synthesis. Thus, components of the RNA degradosome and ribosome assembly are spatiotemporally organized in Caulobacter, with chromosomal readout serving as the template for this organization.}, } @article {pmid29610351, year = {2018}, author = {Scheurer, MS and Chatterjee, S and Wu, W and Ferrero, M and Georges, A and Sachdev, S}, title = {Topological order in the pseudogap metal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3665-E3672}, pmid = {29610351}, issn = {1091-6490}, support = {319286//European Research Council/International ; }, abstract = {We compute the electronic Green's function of the topologically ordered Higgs phase of a SU(2) gauge theory of fluctuating antiferromagnetism on the square lattice. The results are compared with cluster extensions of dynamical mean field theory, and quantum Monte Carlo calculations, on the pseudogap phase of the strongly interacting hole-doped Hubbard model. Good agreement is found in the momentum, frequency, hopping, and doping dependencies of the spectral function and electronic self-energy. We show that lines of (approximate) zeros of the zero-frequency electronic Green's function are signs of the underlying topological order of the gauge theory and describe how these lines of zeros appear in our theory of the Hubbard model. We also derive a modified, nonperturbative version of the Luttinger theorem that holds in the Higgs phase.}, } @article {pmid29610350, year = {2018}, author = {Smith, AS and Nowak, RB and Zhou, S and Giannetto, M and Gokhin, DS and Papoin, J and Ghiran, IC and Blanc, L and Wan, J and Fowler, VM}, title = {Myosin IIA interacts with the spectrin-actin membrane skeleton to control red blood cell membrane curvature and deformability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {E4377-E4385}, pmid = {29610350}, issn = {1091-6490}, support = {UL1 TR001114/TR/NCATS NIH HHS/United States ; U01 HL126497/HL/NHLBI NIH HHS/United States ; R01 GM034225/GM/NIGMS NIH HHS/United States ; R01 HL083464/HL/NHLBI NIH HHS/United States ; R01 HL134043/HL/NHLBI NIH HHS/United States ; TL1 TR001113/TR/NCATS NIH HHS/United States ; }, mesh = {Actins/*metabolism ; Adenosine Triphosphate/metabolism ; Cell Shape/drug effects/*physiology ; Erythrocyte Membrane/*metabolism ; Heterocyclic Compounds, 4 or More Rings/pharmacology ; Humans ; Nonmuscle Myosin Type IIA/*metabolism ; }, abstract = {The biconcave disk shape and deformability of mammalian RBCs rely on the membrane skeleton, a viscoelastic network of short, membrane-associated actin filaments (F-actin) cross-linked by long, flexible spectrin tetramers. Nonmuscle myosin II (NMII) motors exert force on diverse F-actin networks to control cell shapes, but a function for NMII contractility in the 2D spectrin-F-actin network of RBCs has not been tested. Here, we show that RBCs contain membrane skeleton-associated NMIIA puncta, identified as bipolar filaments by superresolution fluorescence microscopy. MgATP disrupts NMIIA association with the membrane skeleton, consistent with NMIIA motor domains binding to membrane skeleton F-actin and contributing to membrane mechanical properties. In addition, the phosphorylation of the RBC NMIIA heavy and light chains in vivo indicates active regulation of NMIIA motor activity and filament assembly, while reduced heavy chain phosphorylation of membrane skeleton-associated NMIIA indicates assembly of stable filaments at the membrane. Treatment of RBCs with blebbistatin, an inhibitor of NMII motor activity, decreases the number of NMIIA filaments associated with the membrane and enhances local, nanoscale membrane oscillations, suggesting decreased membrane tension. Blebbistatin-treated RBCs also exhibit elongated shapes, loss of membrane curvature, and enhanced deformability, indicating a role for NMIIA contractility in promoting membrane stiffness and maintaining RBC biconcave disk cell shape. As structures similar to the RBC membrane skeleton exist in many metazoan cell types, these data demonstrate a general function for NMII in controlling specialized membrane morphology and mechanical properties through contractile interactions with short F-actin in spectrin-F-actin networks.}, } @article {pmid29610349, year = {2018}, author = {Fruchart, M and Jeon, SY and Hur, K and Cheianov, V and Wiesner, U and Vitelli, V}, title = {Soft self-assembly of Weyl materials for light and sound.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3655-E3664}, pmid = {29610349}, issn = {1091-6490}, abstract = {Soft materials can self-assemble into highly structured phases that replicate at the mesoscopic scale the symmetry of atomic crystals. As such, they offer an unparalleled platform to design mesostructured materials for light and sound. Here, we present a bottom-up approach based on self-assembly to engineer 3D photonic and phononic crystals with topologically protected Weyl points. In addition to angular and frequency selectivity of their bulk optical response, Weyl materials are endowed with topological surface states, which allow for the existence of one-way channels, even in the presence of time-reversal invariance. Using a combination of group-theoretical methods and numerical simulations, we identify the general symmetry constraints that a self-assembled structure has to satisfy to host Weyl points and describe how to achieve such constraints using a symmetry-driven pipeline for self-assembled material design and discovery. We illustrate our general approach using block copolymer self-assembly as a model system.}, } @article {pmid29610348, year = {2018}, author = {Brynildsen, JK and Lee, BG and Perron, IJ and Jin, S and Kim, SF and Blendy, JA}, title = {Activation of AMPK by metformin improves withdrawal signs precipitated by nicotine withdrawal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4282-4287}, pmid = {29610348}, issn = {1091-6490}, support = {R01 DA041180/DA/NIDA NIH HHS/United States ; R01 DK084336/DK/NIDDK NIH HHS/United States ; T32 GM008076/GM/NIGMS NIH HHS/United States ; TL1 TR000138/TR/NCATS NIH HHS/United States ; }, mesh = {AMP-Activated Protein Kinases/*drug effects/genetics/physiology ; Aminoimidazole Carboxamide/analogs & derivatives/pharmacology ; Animals ; Anxiety Disorders/chemically induced/*drug therapy/enzymology ; Drug Evaluation, Preclinical ; Enzyme Activation/drug effects ; Feeding Behavior/drug effects ; Gene Knockdown Techniques ; Hippocampus/*drug effects/enzymology ; Male ; Metformin/pharmacology/*therapeutic use ; Mice ; Mice, 129 Strain ; Mice, Inbred C57BL ; Nerve Tissue Proteins/*drug effects/physiology ; Nicotine/*adverse effects ; Ribonucleotides/pharmacology ; Signal Transduction/drug effects ; Substance Withdrawal Syndrome/*drug therapy/enzymology ; Tobacco Use Disorder/enzymology/psychology ; }, abstract = {Cigarette smoking is the leading cause of preventable disease and death in the United States, with more persons dying from nicotine addiction than any other preventable cause of death. Even though smoking cessation incurs multiple health benefits, the abstinence rate remains low with current medications. Here we show that the AMP-activated protein kinase (AMPK) pathway in the hippocampus is activated following chronic nicotine use, an effect that is rapidly reversed by nicotine withdrawal. Increasing pAMPK levels and, consequently, downstream AMPK signaling pharmacologically attenuate anxiety-like behavior following nicotine withdrawal. We show that metformin, a known AMPK activator in the periphery, reduces withdrawal symptoms through a mechanism dependent on the presence of the AMPKα subunits within the hippocampus. This study provides evidence of a direct effect of AMPK modulation on nicotine withdrawal symptoms and suggests central AMPK activation as a therapeutic target for smoking cessation.}, } @article {pmid29610347, year = {2018}, author = {Buddhiraju, S and Santhanam, P and Fan, S}, title = {Thermodynamic limits of energy harvesting from outgoing thermal radiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3609-E3615}, pmid = {29610347}, issn = {1091-6490}, abstract = {We derive the thermodynamic limits of harvesting power from the outgoing thermal radiation from the ambient to the cold outer space. The derivations are based on a duality relation between thermal engines that harvest solar radiation and those that harvest outgoing thermal radiation. In particular, we derive the ultimate limit for harvesting outgoing thermal radiation, which is analogous to the Landsberg limit for solar energy harvesting, and show that the ultimate limit far exceeds what was previously thought to be possible. As an extension of our work, we also derive the ultimate limit of efficiency of thermophotovoltaic systems.}, } @article {pmid29610346, year = {2018}, author = {Hackett, BA and Cherry, S}, title = {Flavivirus internalization is regulated by a size-dependent endocytic pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4246-4251}, pmid = {29610346}, issn = {1091-6490}, support = {R01 AI074951/AI/NIAID NIH HHS/United States ; R01 AI095500/AI/NIAID NIH HHS/United States ; R01 AI122749/AI/NIAID NIH HHS/United States ; }, mesh = {Antigens, Surface/genetics/physiology ; Cell Line, Tumor ; Dengue Virus/physiology ; Endocytosis/drug effects/physiology ; Endoribonucleases/physiology ; Ethers/pharmacology ; Flavivirus/*physiology ; GPI-Linked Proteins/deficiency/genetics/physiology ; Gene Knockdown Techniques ; Humans ; Microspheres ; Microtubule-Associated Proteins/physiology ; Microtubules/drug effects/physiology ; Nocodazole/pharmacology ; Spiro Compounds/pharmacology ; Transferrin ; *Virus Internalization ; West Nile virus/physiology ; Zika Virus/physiology ; }, abstract = {Flaviviruses enter host cells through the process of clathrin-mediated endocytosis, and the spectrum of host factors required for this process are incompletely understood. Here we found that lymphocyte antigen 6 locus E (LY6E) promotes the internalization of multiple flaviviruses, including West Nile virus, Zika virus, and dengue virus. Perhaps surprisingly, LY6E is dispensable for the internalization of the endogenous cargo transferrin, which is also dependent on clathrin-mediated endocytosis for uptake. Since viruses are substantially larger than transferrin, we reasoned that LY6E may be required for uptake of larger cargoes and tested this using transferrin-coated beads of similar size as flaviviruses. LY6E was indeed required for the internalization of transferrin-coated beads, suggesting that LY6E is selectively required for large cargo. Cell biological studies found that LY6E forms tubules upon viral infection and bead internalization, and we found that tubule formation was dependent on RNASEK, which is also required for flavivirus internalization, but not transferrin uptake. Indeed, we found that RNASEK is also required for the internalization of transferrin-coated beads, suggesting it functions upstream of LY6E. These LY6E tubules resembled microtubules, and we found that microtubule assembly was required for their formation and flavivirus uptake. Since microtubule end-binding proteins link microtubules to downstream activities, we screened the three end-binding proteins and found that EB3 promotes virus uptake and LY6E tubularization. Taken together, these results highlight a specialized pathway required for the uptake of large clathrin-dependent endocytosis cargoes, including flaviviruses.}, } @article {pmid29610345, year = {2018}, author = {Wilhelm, P and Schedlbauer, J and Hinderer, F and Hennen, D and Höger, S and Vogelsang, J and Lupton, JM}, title = {Molecular excitonic seesaws.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3626-E3634}, pmid = {29610345}, issn = {1091-6490}, abstract = {The breaking of molecular symmetry through photoexcitation is a ubiquitous but rather elusive process, which, for example, controls the microscopic efficiency of light harvesting in molecular aggregates. A molecular excitation within a π-conjugated segment will self-localize due to strong coupling to molecular vibrations, locally changing bond alternation in a process which is fundamentally nondeterministic. Probing such symmetry breaking usually relies on polarization-resolved fluorescence, which is most powerful on the level of single molecules. Here, we explore symmetry breaking by designing a large, asymmetric acceptor-donor-acceptor (A1-D-A2) complex 10 nm in length, where excitation energy can flow from the donor, a π-conjugated oligomer, to either one of the two boron-dipyrromethene (bodipy) dye acceptors of different color. Fluorescence correlation spectroscopy (FCS) reveals a nondeterministic switching between the energy-transfer pathways from the oligomer to the two acceptor groups on the submillisecond timescale. We conclude that excitation energy transfer, and light harvesting in general, are fundamentally nondeterministic processes, which can be strongly perturbed by external stimuli. A simple demonstration of the relation between exciton localization within the extended π-system and energy transfer to the endcap is given by considering the selectivity of endcap emission through the polarization of the excitation light in triads with bent oligomer backbones. Bending leads to increased localization so that the molecule acquires bichromophoric characteristics in terms of its fluorescence photon statistics.}, } @article {pmid29610344, year = {2018}, author = {Peel, L and Delvenne, JC and Lambiotte, R}, title = {Multiscale mixing patterns in networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4057-4062}, pmid = {29610344}, issn = {1091-6490}, abstract = {Assortative mixing in networks is the tendency for nodes with the same attributes, or metadata, to link to each other. It is a property often found in social networks, manifesting as a higher tendency of links occurring between people of the same age, race, or political belief. Quantifying the level of assortativity or disassortativity (the preference of linking to nodes with different attributes) can shed light on the organization of complex networks. It is common practice to measure the level of assortativity according to the assortativity coefficient, or modularity in the case of categorical metadata. This global value is the average level of assortativity across the network and may not be a representative statistic when mixing patterns are heterogeneous. For example, a social network spanning the globe may exhibit local differences in mixing patterns as a consequence of differences in cultural norms. Here, we introduce an approach to localize this global measure so that we can describe the assortativity, across multiple scales, at the node level. Consequently, we are able to capture and qualitatively evaluate the distribution of mixing patterns in the network. We find that, for many real-world networks, the distribution of assortativity is skewed, overdispersed, and multimodal. Our method provides a clearer lens through which we can more closely examine mixing patterns in networks.}, } @article {pmid29610343, year = {2018}, author = {Sánchez-Iranzo, H and Galardi-Castilla, M and Sanz-Morejón, A and González-Rosa, JM and Costa, R and Ernst, A and Sainz de Aja, J and Langa, X and Mercader, N}, title = {Transient fibrosis resolves via fibroblast inactivation in the regenerating zebrafish heart.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4188-4193}, pmid = {29610343}, issn = {1091-6490}, support = {337703//European Research Council/International ; }, mesh = {Animals ; Animals, Genetically Modified ; Base Sequence ; Cell Adhesion Molecules/biosynthesis ; Cell Lineage ; Cold Temperature/adverse effects ; Collagen Type XII/biosynthesis/genetics ; Endocardium/pathology ; Extracellular Matrix/metabolism ; Fibroblasts/*physiology ; Fibrosis ; Gene Expression Regulation ; Genes, Reporter ; Heart/*physiology ; Heart Injuries/genetics/physiopathology ; Myocardium/pathology ; Myocytes, Cardiac/metabolism/pathology ; RNA, Messenger/biosynthesis ; Regeneration/*physiology ; Transcriptome ; Zebrafish ; Zebrafish Proteins/biosynthesis/genetics ; }, abstract = {In the zebrafish (Danio rerio), regeneration and fibrosis after cardiac injury are not mutually exclusive responses. Upon cardiac cryoinjury, collagen and other extracellular matrix (ECM) proteins accumulate at the injury site. However, in contrast to the situation in mammals, fibrosis is transient in zebrafish and its regression is concomitant with regrowth of the myocardial wall. Little is known about the cells producing this fibrotic tissue or how it resolves. Using novel genetic tools to mark periostin b- and collagen 1alpha2 (col1a2)-expressing cells in combination with transcriptome analysis, we explored the sources of activated fibroblasts and traced their fate. We describe that during fibrosis regression, fibroblasts are not fully eliminated but become inactivated. Unexpectedly, limiting the fibrotic response by genetic ablation of col1a2-expressing cells impaired cardiomyocyte proliferation. We conclude that ECM-producing cells are key players in the regenerative process and suggest that antifibrotic therapies might be less efficient than strategies targeting fibroblast inactivation.}, } @article {pmid29610342, year = {2018}, author = {Dai, DP and Gan, W and Hayakawa, H and Zhu, JL and Zhang, XQ and Hu, GX and Xu, T and Jiang, ZL and Zhang, LQ and Hu, XD and Nie, B and Zhou, Y and Li, J and Zhou, XY and Li, J and Zhang, TM and He, Q and Liu, DG and Chen, HB and Yang, N and Zuo, PP and Zhang, ZX and Yang, HM and Wang, Y and Wilson, SH and Zeng, YX and Wang, JY and Sekiguchi, M and Cai, JP}, title = {Transcriptional mutagenesis mediated by 8-oxoG induces translational errors in mammalian cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4218-4222}, pmid = {29610342}, issn = {1091-6490}, support = {Z01 ES050159/ES/NIEHS NIH HHS/United States ; }, mesh = {Amyloid beta-Peptides/genetics ; Anticodon/genetics ; Base Pairing ; Codon, Nonsense ; DNA Repair Enzymes/antagonists & inhibitors/genetics ; Gene Knockdown Techniques ; Genes, Reporter ; Guanine/*analogs & derivatives/chemistry ; HeLa Cells ; Humans ; Luciferases/genetics ; Mutagenesis/*genetics ; Phosphoric Monoester Hydrolases/antagonists & inhibitors/genetics ; Protein Biosynthesis/*genetics ; RNA Interference ; RNA, Messenger/biosynthesis/genetics ; RNA, Small Interfering/genetics ; Reactive Oxygen Species ; Transcription, Genetic/*genetics ; }, abstract = {Reactive oxygen species formed within the mammalian cell can produce 8-oxo-7,8-dihydroguanine (8-oxoG) in mRNA, which can cause base mispairing during gene expression. Here we found that administration of 8-oxoGTP in MTH1-knockdown cells results in increased 8-oxoG content in mRNA. Under this condition, an amber mutation of the reporter luciferase is suppressed. Using second-generation sequencing techniques, we found that U-to-G changes at preassigned sites of the luciferase transcript increased when 8-oxoGTP was supplied. In addition, an increased level of 8-oxoG content in RNA induced the accumulation of aggregable amyloid β peptides in cells expressing amyloid precursor protein. Our findings indicate that 8-oxoG accumulation in mRNA can alter protein synthesis in mammalian cells. Further work is required to assess the significance of these findings under normal physiological conditions.}, } @article {pmid29610341, year = {2018}, author = {Younis, S and Kamel, W and Falkeborn, T and Wang, H and Yu, D and Daniels, R and Essand, M and Hinkula, J and Akusjärvi, G and Andersson, L}, title = {Multiple nuclear-replicating viruses require the stress-induced protein ZC3H11A for efficient growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3808-E3816}, pmid = {29610341}, issn = {1091-6490}, mesh = {Adenoviruses, Human/genetics/physiology ; Binding Sites ; Biological Transport ; CRISPR-Cas Systems ; Cell Nucleus/metabolism/*virology ; Cytoplasm/virology ; Gene Knockout Techniques ; HeLa Cells ; Heat-Shock Response/genetics/physiology ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Humans ; Nuclear Proteins/antagonists & inhibitors/*physiology ; Protein Domains ; Protein Stability ; RNA, Messenger/*metabolism ; RNA, Viral/*metabolism ; RNA-Binding Proteins/antagonists & inhibitors/*physiology ; Serine-Arginine Splicing Factors/physiology ; *Virus Replication ; Zinc Fingers/*physiology ; }, abstract = {The zinc finger CCCH-type containing 11A (ZC3H11A) gene encodes a well-conserved zinc finger protein that may function in mRNA export as it has been shown to associate with the transcription export (TREX) complex in proteomic screens. Here, we report that ZC3H11A is a stress-induced nuclear protein with RNA-binding capacity that localizes to nuclear splicing speckles. During an adenovirus infection, the ZC3H11A protein and splicing factor SRSF2 relocalize to nuclear regions where viral DNA replication and transcription take place. Knockout (KO) of ZC3H11A in HeLa cells demonstrated that several nuclear-replicating viruses are dependent on ZC3H11A for efficient growth (HIV, influenza virus, herpes simplex virus, and adenovirus), whereas cytoplasmic replicating viruses are not (vaccinia virus and Semliki Forest virus). High-throughput sequencing of ZC3H11A-cross-linked RNA showed that ZC3H11A binds to short purine-rich ribonucleotide stretches in cellular and adenoviral transcripts. We show that the RNA-binding property of ZC3H11A is crucial for its function and localization. In ZC3H11A KO cells, the adenovirus fiber mRNA accumulates in the cell nucleus. Our results suggest that ZC3H11A is important for maintaining nuclear export of mRNAs during stress and that several nuclear-replicating viruses take advantage of this mechanism to facilitate their replication.}, } @article {pmid29610340, year = {2018}, author = {Birzu, G and Hallatschek, O and Korolev, KS}, title = {Fluctuations uncover a distinct class of traveling waves.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3645-E3654}, pmid = {29610340}, issn = {1091-6490}, mesh = {Computer Simulation ; Genetics, Population ; Mathematics ; Models, Genetic ; *Models, Theoretical ; *Physical Phenomena ; }, abstract = {Epidemics, flame propagation, and cardiac rhythms are classic examples of reaction-diffusion waves that describe a switch from one alternative state to another. Only two types of waves are known: pulled, driven by the leading edge, and pushed, driven by the bulk of the wave. Here, we report a distinct class of semipushed waves for which both the bulk and the leading edge contribute to the dynamics. These hybrid waves have the kinetics of pushed waves, but exhibit giant fluctuations similar to pulled waves. The transitions between pulled, semipushed, and fully pushed waves occur at universal ratios of the wave velocity to the Fisher velocity. We derive these results in the context of a species invading a new habitat by examining front diffusion, rate of diversity loss, and fluctuation-induced corrections to the expansion velocity. All three quantities decrease as a power law of the population density with the same exponent. We analytically calculate this exponent, taking into account the fluctuations in the shape of the wave front. For fully pushed waves, the exponent is -1, consistent with the central limit theorem. In semipushed waves, however, the fluctuations average out much more slowly, and the exponent approaches 0 toward the transition to pulled waves. As a result, a rapid loss of genetic diversity and large fluctuations in the position of the front occur, even for populations with cooperative growth and other forms of an Allee effect. The evolutionary outcome of spatial spreading in such populations could therefore be less predictable than previously thought.}, } @article {pmid29610339, year = {2018}, author = {Logan, SL and Thomas, J and Yan, J and Baker, RP and Shields, DS and Xavier, JB and Hammer, BK and Parthasarathy, R}, title = {The Vibrio cholerae type VI secretion system can modulate host intestinal mechanics to displace gut bacterial symbionts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3779-E3787}, pmid = {29610339}, issn = {1091-6490}, support = {P01 HD022486/HD/NICHD NIH HHS/United States ; P50 GM098911/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/physiology ; Aeromonas veronii ; Animals ; Antibiosis/*physiology ; Bacterial Proteins/physiology ; *Gastrointestinal Microbiome ; Gastrointestinal Motility ; Germ-Free Life ; Host-Pathogen Interactions ; Symbiosis ; Type VI Secretion Systems/*physiology ; Vibrio cholerae/pathogenicity/*physiology ; Zebrafish/*microbiology ; }, abstract = {Host-associated microbiota help defend against bacterial pathogens; however, the mechanisms by which pathogens overcome this defense remain largely unknown. We developed a zebrafish model and used live imaging to directly study how the human pathogen Vibrio cholerae invades the intestine. The gut microbiota of fish monocolonized by symbiotic strain Aeromonas veronii was displaced by V. cholerae expressing its type VI secretion system (T6SS), a syringe-like apparatus that deploys effector proteins into target cells. Surprisingly, displacement was independent of T6SS-mediated killing of A. veronii, driven instead by T6SS-induced enhancement of zebrafish intestinal movements that led to expulsion of the resident microbiota by the host. Deleting an actin cross-linking domain from the T6SS apparatus returned intestinal motility to normal and thwarted expulsion, without weakening V. cholerae's ability to kill A. veronii in vitro. Our finding that bacteria can manipulate host physiology to influence intermicrobial competition has implications for both pathogenesis and microbiome engineering.}, } @article {pmid29610338, year = {2018}, author = {Sabine, CL}, title = {Good news and bad news of blue carbon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3745-3746}, pmid = {29610338}, issn = {1091-6490}, mesh = {*Carbon ; Communication ; *Physician-Patient Relations ; }, } @article {pmid29610337, year = {2018}, author = {Ponce de León, MS and Koesbardiati, T and Weissmann, JD and Milella, M and Reyna-Blanco, CS and Suwa, G and Kondo, O and Malaspinas, AS and White, TD and Zollikofer, CPE}, title = {Human bony labyrinth is an indicator of population history and dispersal from Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4128-4133}, pmid = {29610337}, issn = {1091-6490}, mesh = {Africa ; Anatomy, Comparative ; Animals ; *Biological Evolution ; Cephalometry/methods ; Ear, Inner/*anatomy & histology/diagnostic imaging ; History, Ancient ; Human Genome Project ; Human Migration/*history ; Humans ; Imaging, Three-Dimensional ; Phenotype ; Primates/anatomy & histology ; Tomography, X-Ray Computed ; }, abstract = {The dispersal of modern humans from Africa is now well documented with genetic data that track population history, as well as gene flow between populations. Phenetic skeletal data, such as cranial and pelvic morphologies, also exhibit a dispersal-from-Africa signal, which, however, tends to be blurred by the effects of local adaptation and in vivo phenotypic plasticity, and that is often deteriorated by postmortem damage to skeletal remains. These complexities raise the question of which skeletal structures most effectively track neutral population history. The cavity system of the inner ear (the so-called bony labyrinth) is a good candidate structure for such analyses. It is already fully formed by birth, which minimizes postnatal phenotypic plasticity, and it is generally well preserved in archaeological samples. Here we use morphometric data of the bony labyrinth to show that it is a surprisingly good marker of the global dispersal of modern humans from Africa. Labyrinthine morphology tracks genetic distances and geography in accordance with an isolation-by-distance model with dispersal from Africa. Our data further indicate that the neutral-like pattern of variation is compatible with stabilizing selection on labyrinth morphology. Given the increasingly important role of the petrous bone for ancient DNA recovery from archaeological specimens, we encourage researchers to acquire 3D morphological data of the inner ear structures before any invasive sampling. Such data will constitute an important archive of phenotypic variation in present and past populations, and will permit individual-based genotype-phenotype comparisons.}, } @article {pmid29610336, year = {2018}, author = {Smith, HL and Goebel, T}, title = {Origins and spread of fluted-point technology in the Canadian Ice-Free Corridor and eastern Beringia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4116-4121}, pmid = {29610336}, issn = {1091-6490}, abstract = {Fluted projectile points have long been recognized as the archaeological signature of early humans dispersing throughout the Western Hemisphere; however, we still lack a clear understanding of their appearance in the interior "Ice-Free Corridor" of western Canada and eastern Beringia. To solve this problem, we conducted a geometric morphometric shape analysis and a phylogenetic analysis of technological traits on fluted points from the archaeological records of northern Alaska and Yukon, in combination with artifacts from further south in Canada, the Great Plains, and eastern United States to investigate the plausibility of historical relatedness and evolutionary patterns in the spread of fluted-point technology in the latest Pleistocene and earliest Holocene. Results link morphologies and technologies of Clovis, certain western Canadian, and northern fluted points, suggesting that fluting technology arrived in the Arctic from a proximate source in the interior Ice-Free Corridor and ultimately from the earliest populations in temperate North America, complementing new genomic models explaining the peopling of the Americas.}, } @article {pmid29610335, year = {2018}, author = {Wang, L and Chen, H and Wang, C and Hu, Z and Yan, S}, title = {Negative regulator of E2F transcription factors links cell cycle checkpoint and DNA damage repair.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3837-E3845}, pmid = {29610335}, issn = {1091-6490}, mesh = {Arabidopsis/cytology/*genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism/*physiology ; Cell Cycle Checkpoints/*genetics ; DNA Damage ; DNA Repair/*genetics ; E2F Transcription Factors/chemistry/*physiology ; *Gene Expression Regulation, Plant ; Nuclear Proteins/genetics/metabolism/*physiology ; Plant Roots/genetics/growth & development/metabolism ; Protein Domains ; }, abstract = {DNA damage poses a serious threat to genome integrity and greatly affects growth and development. To maintain genome stability, all organisms have evolved elaborate DNA damage response mechanisms including activation of cell cycle checkpoints and DNA repair. Here, we show that the DNA repair protein SNI1, a subunit of the evolutionally conserved SMC5/6 complex, directly links these two processes in Arabidopsis SNI1 binds to the activation domains of E2F transcription factors, the key regulators of cell cycle progression, and represses their transcriptional activities. In turn, E2Fs activate the expression of SNI1, suggesting that E2Fs and SNI1 form a negative feedback loop. Genetically, overexpression of SNI1 suppresses the phenotypes of E2F-overexpressing plants, and loss of E2F function fully suppresses the sni1 mutant, indicating that SNI1 is necessary and sufficient to inhibit E2Fs. Altogether, our study revealed that SNI1 is a negative regulator of E2Fs and plays dual roles in DNA damage responses by linking cell cycle checkpoint and DNA repair.}, } @article {pmid29610334, year = {2018}, author = {Möller, S and du Plessis, L and Stadler, T}, title = {Impact of the tree prior on estimating clock rates during epidemic outbreaks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4200-4205}, pmid = {29610334}, issn = {1091-6490}, mesh = {Bayes Theorem ; Bias ; *Biological Evolution ; Calibration ; *Computer Simulation ; Ebolavirus/*genetics ; *Epidemics ; Evolution, Molecular ; Genetics, Population/*methods ; Humans ; *Models, Genetic ; *Mutation Rate ; *Phylogeny ; Sierra Leone ; }, abstract = {Bayesian phylogenetics aims at estimating phylogenetic trees together with evolutionary and population dynamic parameters based on genetic sequences. It has been noted that the clock rate, one of the evolutionary parameters, decreases with an increase in the sampling period of sequences. In particular, clock rates of epidemic outbreaks are often estimated to be higher compared with the long-term clock rate. Purifying selection has been suggested as a biological factor that contributes to this phenomenon, since it purges slightly deleterious mutations from a population over time. However, other factors such as methodological biases may also play a role and make a biological interpretation of results difficult. In this paper, we identify methodological biases originating from the choice of tree prior, that is, the model specifying epidemiological dynamics. With a simulation study we demonstrate that a misspecification of the tree prior can upwardly bias the inferred clock rate and that the interplay of the different models involved in the inference can be complex and nonintuitive. We also show that the choice of tree prior can influence the inference of clock rate on real-world Ebola virus (EBOV) datasets. While commonly used tree priors result in very high clock-rate estimates for sequences from the initial phase of the epidemic in Sierra Leone, tree priors allowing for population structure lead to estimates agreeing with the long-term rate for EBOV.}, } @article {pmid29610333, year = {2018}, author = {Maslowska, KH and Makiela-Dzbenska, K and Mo, JY and Fijalkowska, IJ and Schaaper, RM}, title = {High-accuracy lagging-strand DNA replication mediated by DNA polymerase dissociation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4212-4217}, pmid = {29610333}, issn = {1091-6490}, support = {Z01 ES065086/ES/NIEHS NIH HHS/United States ; }, mesh = {Chromosomes, Bacterial/genetics ; DNA/metabolism ; DNA Polymerase III/genetics/*metabolism ; *DNA Replication ; DNA, Bacterial/genetics/metabolism ; Escherichia coli Proteins/genetics ; Lac Operon ; Lac Repressors/genetics ; *Mutagenesis ; Mutation Rate ; }, abstract = {The fidelity of DNA replication is a critical factor in the rate at which cells incur mutations. Due to the antiparallel orientation of the two chromosomal DNA strands, one strand (leading strand) is replicated in a mostly processive manner, while the other (lagging strand) is synthesized in short sections called Okazaki fragments. A fundamental question that remains to be answered is whether the two strands are copied with the same intrinsic fidelity. In most experimental systems, this question is difficult to answer, as the replication complex contains a different DNA polymerase for each strand, such as, for example, DNA polymerases δ and ε in eukaryotes. Here we have investigated this question in the bacterium Escherichia coli, in which the replicase (DNA polymerase III holoenzyme) contains two copies of the same polymerase (Pol III, the dnaE gene product), and hence the two strands are copied by the same polymerase. Our in vivo mutagenesis data indicate that the two DNA strands are not copied with the same accuracy, and that, remarkably, the lagging strand has the highest fidelity. We postulate that this effect results from the greater dissociative character of the lagging-strand polymerase, which provides additional options for error removal. Our conclusion is strongly supported by results with dnaE antimutator polymerases characterized by increased dissociation rates.}, } @article {pmid29610332, year = {2018}, author = {Rastogi, C and Rube, HT and Kribelbauer, JF and Crocker, J and Loker, RE and Martini, GD and Laptenko, O and Freed-Pastor, WA and Prives, C and Stern, DL and Mann, RS and Bussemaker, HJ}, title = {Accurate and sensitive quantification of protein-DNA binding affinity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3692-E3701}, pmid = {29610332}, issn = {1091-6490}, support = {R01 HG003008/HG/NHGRI NIH HHS/United States ; R35 GM118336/GM/NIGMS NIH HHS/United States ; G20 RR030893/RR/NCRR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 GM007088/GM/NIGMS NIH HHS/United States ; P01 CA087497/CA/NCI NIH HHS/United States ; T32 GM008224/GM/NIGMS NIH HHS/United States ; R01 CA196234/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; DNA/*metabolism ; DNA Footprinting/*methods ; DNA-Binding Proteins/*metabolism ; Datasets as Topic ; Drosophila Proteins/metabolism ; Electrophoretic Mobility Shift Assay ; Enhancer Elements, Genetic ; Gene Library ; Homeodomain Proteins/metabolism ; Humans ; Models, Molecular ; Protein Binding ; Protein Conformation ; Recombinant Proteins/metabolism ; Transcription Factors/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Transcription factors (TFs) control gene expression by binding to genomic DNA in a sequence-specific manner. Mutations in TF binding sites are increasingly found to be associated with human disease, yet we currently lack robust methods to predict these sites. Here, we developed a versatile maximum likelihood framework named No Read Left Behind (NRLB) that infers a biophysical model of protein-DNA recognition across the full affinity range from a library of in vitro selected DNA binding sites. NRLB predicts human Max homodimer binding in near-perfect agreement with existing low-throughput measurements. It can capture the specificity of the p53 tetramer and distinguish multiple binding modes within a single sample. Additionally, we confirm that newly identified low-affinity enhancer binding sites are functional in vivo, and that their contribution to gene expression matches their predicted affinity. Our results establish a powerful paradigm for identifying protein binding sites and interpreting gene regulatory sequences in eukaryotic genomes.}, } @article {pmid29610331, year = {2018}, author = {Letelier, J and Terriente, J and Belzunce, I and Voltes, A and Undurraga, CA and Polvillo, R and Devos, L and Tena, JJ and Maeso, I and Retaux, S and Gomez-Skarmeta, JL and Martínez-Morales, JR and Pujades, C}, title = {Evolutionary emergence of the rac3b/rfng/sgca regulatory cluster refined mechanisms for hindbrain boundaries formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3731-E3740}, pmid = {29610331}, issn = {1091-6490}, mesh = {Actomyosin/*physiology ; Animals ; Body Patterning/genetics ; CRISPR-Cas Systems ; Cell Movement ; Characidae/genetics/physiology ; Chromatin/genetics/ultrastructure ; Evolution, Molecular ; Fishes/classification/genetics ; *Gene Expression Regulation, Developmental ; Morphogenesis ; Mutagenesis, Site-Directed ; Neurogenesis ; Phylogeny ; Rhombencephalon/*embryology ; Sarcoglycans/genetics/*physiology ; Species Specificity ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*physiology ; rac GTP-Binding Proteins/genetics/*physiology ; }, abstract = {Developmental programs often rely on parallel morphogenetic mechanisms that guarantee precise tissue architecture. While redundancy constitutes an obvious selective advantage, little is known on how novel morphogenetic mechanisms emerge during evolution. In zebrafish, rhombomeric boundaries behave as an elastic barrier, preventing cell intermingling between adjacent compartments. Here, we identify the fundamental role of the small-GTPase Rac3b in actomyosin cable assembly at hindbrain boundaries. We show that the novel rac3b/rfng/sgca regulatory cluster, which is specifically expressed at the boundaries, emerged in the Ostariophysi superorder by chromosomal rearrangement that generated new cis-regulatory interactions. By combining 4C-seq, ATAC-seq, transgenesis, and CRISPR-induced deletions, we characterized this regulatory domain, identifying hindbrain boundary-specific cis-regulatory elements. Our results suggest that the capacity of boundaries to act as an elastic mesh for segregating rhombomeric cells evolved by cooption of critical genes to a novel regulatory block, refining the mechanisms for hindbrain segmentation.}, } @article {pmid29610330, year = {2018}, author = {Pacella, SR and Brown, CA and Waldbusser, GG and Labiosa, RG and Hales, B}, title = {Seagrass habitat metabolism increases short-term extremes and long-term offset of CO2 under future ocean acidification.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3870-3875}, pmid = {29610330}, issn = {1091-6490}, mesh = {Carbon Dioxide/*analysis/metabolism ; Carbonates/*analysis/metabolism ; *Ecosystem ; Hydrogen-Ion Concentration ; Oceans and Seas ; Seasons ; Seawater/*chemistry ; Zosteraceae/*metabolism ; }, abstract = {The role of rising atmospheric CO2 in modulating estuarine carbonate system dynamics remains poorly characterized, likely due to myriad processes driving the complex chemistry in these habitats. We reconstructed the full carbonate system of an estuarine seagrass habitat for a summer period of 2.5 months utilizing a combination of time-series observations and mechanistic modeling, and quantified the roles of aerobic metabolism, mixing, and gas exchange in the observed dynamics. The anthropogenic CO2 burden in the habitat was estimated for the years 1765-2100 to quantify changes in observed high-frequency carbonate chemistry dynamics. The addition of anthropogenic CO2 alters the thermodynamic buffer factors (e.g., the Revelle factor) of the carbonate system, decreasing the seagrass habitat's ability to buffer natural carbonate system fluctuations. As a result, the most harmful carbonate system indices for many estuarine organisms [minimum pHT, minimum Ωarag, and maximum pCO2(s.w.)] change up to 1.8×, 2.3×, and 1.5× more rapidly than the medians for each parameter, respectively. In this system, the relative benefits of the seagrass habitat in locally mitigating ocean acidification increase with the higher atmospheric CO2 levels predicted toward 2100. Presently, however, these mitigating effects are mixed due to intense diel cycling of CO2 driven by aerobic metabolism. This study provides estimates of how high-frequency pHT, Ωarag, and pCO2(s.w.) dynamics are altered by rising atmospheric CO2 in an estuarine habitat, and highlights nonlinear responses of coastal carbonate parameters to ocean acidification relevant for water quality management.}, } @article {pmid29610329, year = {2018}, author = {Anderson, CJ and Oakeshott, JG and Tay, WT and Gordon, KHJ and Zwick, A and Walsh, TK}, title = {Hybridization and gene flow in the mega-pest lineage of moth, Helicoverpa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {19}, pages = {5034-5039}, pmid = {29610329}, issn = {1091-6490}, mesh = {Animals ; Chimera/*genetics ; *Gene Flow ; *Genome, Insect ; Insect Proteins/*genetics ; Insecticide Resistance/*genetics ; Moths/*genetics ; Species Specificity ; }, abstract = {Within the mega-pest lineage of heliothine moths are a number of polyphagous, highly mobile species for which the exchange of adaptive traits through hybridization would affect their properties as pests. The recent invasion of South America by one of the most significant agricultural pests, Helicoverpa armigera, raises concerns for the formation of novel combinations of adaptive genes following hybridization with the closely related Helicoverpa zea To investigate the propensity for hybridization within the genus Helicoverpa, we carried out whole-genome resequencing of samples from six species, focusing in particular upon H. armigera population structure and its relationship with H. zea We show that both H. armigera subspecies have greater genetic diversity and effective population sizes than do the other species. We find no signals for gene flow among the six species, other than between H. armigera and H. zea, with nine Brazilian individuals proving to be hybrids of those two species. Eight had largely H. armigera genomes with some introgressed DNA from H. zea scattered throughout. The ninth resembled an F1 hybrid but with stretches of homozygosity for each parental species that reflect previous hybridization. Regions homozygous for H. armigera-derived DNA in this individual included one containing a gustatory receptor and esterase genes previously associated with host range, while another encoded a cytochrome P450 that confers insecticide resistance. Our data point toward the emergence of novel hybrid ecotypes and highlight the importance of monitoring H. armigera genotypes as they spread through the Americas.}, } @article {pmid29610328, year = {2018}, author = {Sakai, A and Matsuda, T and Doi, H and Nagaishi, Y and Kato, K and Nakashima, K}, title = {Ectopic neurogenesis induced by prenatal antiepileptic drug exposure augments seizure susceptibility in adult mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4270-4275}, pmid = {29610328}, issn = {1091-6490}, mesh = {Animals ; Anticonvulsants/administration & dosage/pharmacology/*toxicity ; Cell Movement/drug effects/genetics ; Cells, Cultured ; Dentate Gyrus/drug effects/embryology/pathology ; Disease Susceptibility ; Female ; Gene Expression Regulation, Developmental/drug effects ; Gestational Age ; Hippocampus/embryology/pathology/physiopathology ; Mice ; Mice, Inbred C57BL ; Nerve Tissue Proteins/biosynthesis/genetics ; Neural Stem Cells/drug effects ; Neurogenesis/*drug effects ; Neurons/pathology ; Physical Exertion ; Pregnancy ; *Prenatal Exposure Delayed Effects ; RNA, Messenger/biosynthesis/genetics ; Random Allocation ; Rats ; Receptors, CXCR4/biosynthesis/genetics/therapeutic use ; Seizures/chemically induced/embryology/*etiology ; Transcriptome ; Valproic Acid/administration & dosage/pharmacology/*toxicity ; }, abstract = {Epilepsy is a neurological disorder often associated with seizure that affects ∼0.7% of pregnant women. During pregnancy, most epileptic patients are prescribed antiepileptic drugs (AEDs) such as valproic acid (VPA) to control seizure activity. Here, we show that prenatal exposure to VPA in mice increases seizure susceptibility in adult offspring through mislocalization of newborn neurons in the hippocampus. We confirmed that neurons newly generated from neural stem/progenitor cells (NS/PCs) are integrated into the granular cell layer in the adult hippocampus; however, prenatal VPA treatment altered the expression in NS/PCs of genes associated with cell migration, including CXC motif chemokine receptor 4 (Cxcr4), consequently increasing the ectopic localization of newborn neurons in the hilus. We also found that voluntary exercise in a running wheel suppressed this ectopic neurogenesis and countered the enhanced seizure susceptibility caused by prenatal VPA exposure, probably by normalizing the VPA-disrupted expression of multiple genes including Cxcr4 in adult NS/PCs. Replenishing Cxcr4 expression alone in NS/PCs was sufficient to overcome the aberrant migration of newborn neurons and increased seizure susceptibility in VPA-exposed mice. Thus, prenatal exposure to an AED, VPA, has a long-term effect on the behavior of NS/PCs in offspring, but this effect can be counteracted by a simple physical activity. Our findings offer a step to developing strategies for managing detrimental effects in offspring exposed to VPA in utero.}, } @article {pmid29610327, year = {2018}, author = {Ntai, I and Fornelli, L and DeHart, CJ and Hutton, JE and Doubleday, PF and LeDuc, RD and van Nispen, AJ and Fellers, RT and Whiteley, G and Boja, ES and Rodriguez, H and Kelleher, NL}, title = {Precise characterization of KRAS4b proteoforms in human colorectal cells and tumors reveals mutation/modification cross-talk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4140-4145}, pmid = {29610327}, issn = {1091-6490}, support = {P41 GM108569/GM/NIGMS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; U54 CA193419/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Cell Line, Tumor ; Cell Membrane/metabolism ; Chromatography, Liquid ; Colorectal Neoplasms/*enzymology/genetics ; Cysteine/chemistry ; Humans ; Methylation ; Models, Molecular ; *Mutation, Missense ; Neoplasm Proteins/*analysis/chemistry/isolation & purification ; Nitrosation ; *Point Mutation ; Prenylation ; Protein Conformation ; *Protein Processing, Post-Translational ; Proteomics/methods ; Proto-Oncogene Proteins p21(ras)/*analysis/chemistry/isolation & purification ; Recombinant Proteins/chemistry ; Sequence Alignment ; Sequence Homology, Amino Acid ; Tandem Mass Spectrometry ; }, abstract = {Mutations of the KRAS gene are found in human cancers with high frequency and result in the constitutive activation of its protein products. This leads to aberrant regulation of downstream pathways, promoting cell survival, proliferation, and tumorigenesis that drive cancer progression and negatively affect treatment outcomes. Here, we describe a workflow that can detect and quantify mutation-specific consequences of KRAS biochemistry, namely linked changes in posttranslational modifications (PTMs). We combined immunoaffinity enrichment with detection by top-down mass spectrometry to discover and quantify proteoforms with or without the Gly13Asp mutation (G13D) specifically in the KRAS4b isoform. The workflow was applied first to isogenic KRAS colorectal cancer (CRC) cell lines and then to patient CRC tumors with matching KRAS genotypes. In two cellular models, a direct link between the knockout of the mutant G13D allele and the complete nitrosylation of cysteine 118 of the remaining WT KRAS4b was observed. Analysis of tumor samples quantified the percentage of mutant KRAS4b actually present in cancer tissue and identified major differences in the levels of C-terminal carboxymethylation, a modification critical for membrane association. These data from CRC cells and human tumors suggest mechanisms of posttranslational regulation that are highly context-dependent and which lead to preferential production of specific KRAS4b proteoforms.}, } @article {pmid29610326, year = {2018}, author = {}, title = {Correction for Li et al., Regulator of G protein signaling 5 protects against cardiac hypertrophy and fibrosis during biomechanical stress of pressure overload.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3858-E3861}, doi = {10.1073/pnas.1804573115}, pmid = {29610326}, issn = {1091-6490}, } @article {pmid29610325, year = {2018}, author = {Kadam, RU and Wilson, IA}, title = {A small-molecule fragment that emulates binding of receptor and broadly neutralizing antibodies to influenza A hemagglutinin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4240-4245}, pmid = {29610325}, issn = {1091-6490}, support = {R56 AI117675/AI/NIAID NIH HHS/United States ; R56 AI127371/AI/NIAID NIH HHS/United States ; }, mesh = {Antibodies, Neutralizing/*metabolism ; Antigen-Antibody Reactions/*drug effects ; Antigens, Viral/*metabolism ; Binding Sites/drug effects ; Crystallization ; Crystallography, X-Ray ; Hemagglutinin Glycoproteins, Influenza Virus/*metabolism ; Humans ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Influenza A virus/immunology ; Influenza, Human/immunology ; Models, Molecular ; Molecular Mimicry ; Molecular Structure ; N-Acetylneuraminic Acid/chemistry ; Protein Binding/drug effects ; Protein Conformation ; Receptors, Virus/chemistry ; Taurine/*analogs & derivatives/pharmacology ; }, abstract = {The influenza virus hemagglutinin (HA) glycoprotein mediates receptor binding and membrane fusion during viral entry in host cells. Blocking these key steps in viral infection has applications for development of novel antiinfluenza therapeutics as well as vaccines. However, the lack of structural information on how small molecules can gain a foothold in the small, shallow receptor-binding site (RBS) has hindered drug design against this important target on the viral pathogen. Here, we report on the serendipitous crystallization-based discovery of a small-molecule N-cyclohexyltaurine, commonly known as the buffering agent CHES, that is able to bind to both group-1 and group-2 HAs of influenza A viruses. X-ray structural characterization of group-1 H5N1 A/Vietnam/1203/2004 (H5/Viet) and group-2 H3N2 A/Hong Kong/1/1968 (H3/HK68) HAs at 2.0-Å and 2.57-Å resolution, respectively, revealed that N-cyclohexyltaurine binds to the heart of the conserved HA RBS. N-cyclohexyltaurine mimics the binding mode of the natural receptor sialic acid and RBS-targeting bnAbs through formation of similar hydrogen bonds and CH-π interactions with the HA. In H3/HK68, N-cyclohexyltaurine also binds to a conserved pocket in the stem region, thereby exhibiting a dual-binding mode in group-2 HAs. These long-awaited structural insights into RBS recognition by a noncarbohydrate-based small molecule enhance our knowledge of how to target this important functional site and can serve as a template to guide the development of novel broad-spectrum small-molecule therapeutics against influenza virus.}, } @article {pmid29610324, year = {2018}, author = {Pan, R and Xu, M and Burgess, JD and Jiang, D and Chen, HY}, title = {Direct electrochemical observation of glucosidase activity in isolated single lysosomes from a living cell.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4087-4092}, pmid = {29610324}, issn = {1091-6490}, mesh = {Electrochemical Techniques ; Glucose Oxidase/metabolism ; Glucosidases ; Glucosides/metabolism ; Hydrogen Peroxide/analysis ; Lysosomes/*enzymology ; Nanotubes ; Single-Cell Analysis ; }, abstract = {The protein activity in individual intracellular compartments in single living cells must be analyzed to obtain an understanding of protein function at subcellular locations. The current methodology for probing activity is often not resolved to the level of an individual compartment, and the results provide an extent of reaction that is averaged from a group of compartments. To address this technological limitation, a single lysosome is sorted from a living cell via electrophoresis into a nanocapillary designed to electrochemically analyze internal solution. The activity of a protein specific to lysosomes, β-glucosidase, is determined by the electrochemical quantification of hydrogen peroxide generated from the reaction with its substrate and the associated enzymes preloaded in the nanocapillary. Sorting and assaying multiple lysosomes from the same cell shows the relative homogeneity of protein activity between different lysosomes, whereas the protein activity in single lysosomes from different cells of the same type is heterogeneous. Thus, this study for the analysis of protein activity within targeted cellular compartments allows direct study of protein function at subcellular resolution and provides unprecedented information about the homogeneity within the lysosomal population of a single cell.}, } @article {pmid29610323, year = {2018}, author = {}, title = {Correction for Itkin et al., The biosynthetic pathway of the nonsugar, high-intensity sweetener mogroside V from Siraitia grosvenorii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3862}, doi = {10.1073/pnas.1804875115}, pmid = {29610323}, issn = {1091-6490}, } @article {pmid29610322, year = {2018}, author = {Egeland, CP and Domínguez-Rodrigo, M and Pickering, TR and Menter, CG and Heaton, JL}, title = {Hominin skeletal part abundances and claims of deliberate disposal of corpses in the Middle Pleistocene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4601-4606}, pmid = {29610322}, issn = {1091-6490}, mesh = {Animals ; Anthropology, Cultural/*methods ; Archaeology ; Bone and Bones ; Burial/ethics/*history ; Cadaver ; Ceremonial Behavior ; Fossils/history ; History, Ancient ; Hominidae/*psychology ; Humans ; Machine Learning ; Neanderthals ; South Africa ; Spain ; }, abstract = {Humans are set apart from other organisms by the realization of their own mortality. Thus, determining the prehistoric emergence of this capacity is of significant interest to understanding the uniqueness of the human animal. Tracing that capacity chronologically is possible through archaeological investigations that focus on physical markers that reflect "mortality salience." Among these markers is the deliberate and culturally mediated disposal of corpses. Some Neandertal bone assemblages are among the earliest reasonable claims for the deliberate disposal of hominins, but even these are vigorously debated. More dramatic assertions center on the Middle Pleistocene sites of Sima de los Huesos (SH, Spain) and the Dinaledi Chamber (DC, South Africa), where the remains of multiple hominin individuals were found in deep caves, and under reported taphonomic circumstances that seem to discount the possibility that nonhominin actors and processes contributed to their formation. These claims, with significant implications for charting the evolution of the "human condition," deserve scrutiny. We test these assertions through machine-learning analyses of hominin skeletal part representation in the SH and DC assemblages. Our results indicate that nonanthropogenic agents and abiotic processes cannot yet be ruled out as significant contributors to the ultimate condition of both collections. This finding does not falsify hypotheses of deliberate disposal for the SH and DC corpses, but does indicate that the data also support partially or completely nonanthropogenic formational histories.}, } @article {pmid29610321, year = {2018}, author = {}, title = {Correction for Chen et al., B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3857}, doi = {10.1073/pnas.1804362115}, pmid = {29610321}, issn = {1091-6490}, } @article {pmid29610320, year = {2018}, author = {Tarun, OB and Hannesschläger, C and Pohl, P and Roke, S}, title = {Label-free and charge-sensitive dynamic imaging of lipid membrane hydration on millisecond time scales.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4081-4086}, pmid = {29610320}, issn = {1091-6490}, mesh = {Diffusion ; Hydrophobic and Hydrophilic Interactions ; Lipid Bilayers/*chemistry ; Membrane Lipids/*chemistry ; Membrane Potentials ; Microscopy, Confocal/*methods ; Time Factors ; Water/analysis ; }, abstract = {Biological membranes are highly dynamic and complex lipid bilayers, responsible for the fate of living cells. To achieve this function, the hydrating environment is crucial. However, membrane imaging typically neglects water, focusing on the insertion of probes, resonant responses of lipids, or the hydrophobic core. Owing to a recent improvement of second-harmonic (SH) imaging throughput by three orders of magnitude, we show here that we can use SH microscopy to follow membrane hydration of freestanding lipid bilayers on millisecond time scales. Instead of using the UV/VIS resonant response of specific membrane-inserted fluorophores to record static SH images over time scales of >1,000 s, we SH imaged symmetric and asymmetric lipid membranes, while varying the ionic strength and pH of the adjacent solutions. We show that the nonresonant SH response of water molecules aligned by charge-dipole interactions with charged lipids can be used as a label-free probe of membrane structure and dynamics. Lipid domain diffusion is imaged label-free by means of the hydration of charged domains. The orientational ordering of water is used to construct electrostatic membrane potential maps. The average membrane potential depends quadratically on an applied external bias, which is modeled by nonlinear optical theory. Spatiotemporal fluctuations on the order of 100-mV changes in the membrane potential are seen. These changes imply that membranes are very dynamic, not only in their structure but also in their membrane potential landscape. This may have important consequences for membrane function, mechanical stability, and protein/pore distributions.}, } @article {pmid29610319, year = {2018}, author = {Hsieh, WP and Deschamps, F and Okuchi, T and Lin, JF}, title = {Effects of iron on the lattice thermal conductivity of Earth's deep mantle and implications for mantle dynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4099-4104}, pmid = {29610319}, issn = {1091-6490}, mesh = {*Earth (Planet) ; *Evolution, Planetary ; *Geological Phenomena ; *Iron ; Pressure ; Temperature ; *Thermal Conductivity ; }, abstract = {Iron may critically influence the physical properties and thermochemical structures of Earth's lower mantle. Its effects on thermal conductivity, with possible consequences on heat transfer and mantle dynamics, however, remain largely unknown. We measured the lattice thermal conductivity of lower-mantle ferropericlase to 120 GPa using the ultrafast optical pump-probe technique in a diamond anvil cell. The thermal conductivity of ferropericlase with 56% iron significantly drops by a factor of 1.8 across the spin transition around 53 GPa, while that with 8-10% iron increases monotonically with pressure, causing an enhanced iron substitution effect in the low-spin state. Combined with bridgmanite data, modeling of our results provides a self-consistent radial profile of lower-mantle thermal conductivity, which is dominated by pressure, temperature, and iron effects, and shows a twofold increase from top to bottom of the lower mantle. Such increase in thermal conductivity may delay the cooling of the core, while its decrease with iron content may enhance the dynamics of large low shear-wave velocity provinces. Our findings further show that, if hot and strongly enriched in iron, the seismic ultralow velocity zones have exceptionally low conductivity, thus delaying their cooling.}, } @article {pmid29610318, year = {2018}, author = {Xu, H and Lee, MS and Tsai, PY and Adler, AS and Curry, NL and Challa, S and Freinkman, E and Hitchcock, DS and Copps, KD and White, MF and Bronson, RT and Marcotrigiano, M and Wu, Y and Clish, CB and Kalaany, NY}, title = {Ablation of insulin receptor substrates 1 and 2 suppresses Kras-driven lung tumorigenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4228-4233}, pmid = {29610318}, issn = {1091-6490}, support = {P30 DK040561/DK/NIDDK NIH HHS/United States ; R01 CA211944/CA/NCI NIH HHS/United States ; R01 DK098655/DK/NIDDK NIH HHS/United States ; }, mesh = {A549 Cells ; Amino Acids/metabolism ; Animals ; Autophagy ; Carcinogenesis/*metabolism ; Carcinoma, Non-Small-Cell Lung/genetics/physiopathology/*prevention & control ; Codon, Terminator ; *Genes, ras ; Humans ; Insulin/*pharmacology ; Insulin Receptor Substrate Proteins/deficiency/*physiology ; Insulin-Like Growth Factor I/*physiology ; Lung Neoplasms/genetics/physiopathology/*prevention & control ; Mice ; Neoplasm Proteins/physiology ; Proteolysis ; Proto-Oncogene Proteins c-akt/physiology ; Proto-Oncogene Proteins p21(ras)/*physiology ; Signal Transduction/physiology ; }, abstract = {Non-small-cell lung cancer (NSCLC) is a leading cause of cancer death worldwide, with 25% of cases harboring oncogenic Kirsten rat sarcoma (KRAS). Although KRAS direct binding to and activation of PI3K is required for KRAS-driven lung tumorigenesis, the contribution of insulin receptor (IR) and insulin-like growth factor 1 receptor (IGF1R) in the context of mutant KRAS remains controversial. Here, we provide genetic evidence that lung-specific dual ablation of insulin receptor substrates 1/2 (Irs1/Irs2), which mediate insulin and IGF1 signaling, strongly suppresses tumor initiation and dramatically extends the survival of a mouse model of lung cancer with Kras activation and p53 loss. Mice with Irs1/Irs2 loss eventually succumb to tumor burden, with tumor cells displaying suppressed Akt activation and strikingly diminished intracellular levels of essential amino acids. Acute loss of IRS1/IRS2 or inhibition of IR/IGF1R in KRAS-mutant human NSCLC cells decreases the uptake and lowers the intracellular levels of amino acids, while enhancing basal autophagy and sensitivity to autophagy and proteasome inhibitors. These findings demonstrate that insulin/IGF1 signaling is required for KRAS-mutant lung cancer initiation, and identify decreased amino acid levels as a metabolic vulnerability in tumor cells with IR/IGF1R inhibition. Consequently, combinatorial targeting of IR/IGF1R with autophagy or proteasome inhibitors may represent an effective therapeutic strategy in KRAS-mutant NSCLC.}, } @article {pmid29610317, year = {2018}, author = {Bernard, Q and Smith, AA and Yang, X and Koci, J and Foor, SD and Cramer, SD and Zhuang, X and Dwyer, JE and Lin, YP and Mongodin, EF and Marques, A and Leong, JM and Anguita, J and Pal, U}, title = {Plasticity in early immune evasion strategies of a bacterial pathogen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3788-E3797}, pmid = {29610317}, issn = {1091-6490}, support = {R01 AI080615/AI/NIAID NIH HHS/United States ; R01 AI116620/AI/NIAID NIH HHS/United States ; R03 AI128232/AI/NIAID NIH HHS/United States ; R56 AI080615/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigens, Bacterial/immunology ; Antimicrobial Cationic Peptides/biosynthesis/genetics ; Arachnid Vectors/microbiology ; Bacterial Proteins/genetics/*physiology ; Borrelia burgdorferi/genetics/*immunology/pathogenicity ; Cells, Cultured ; Complement System Proteins/immunology ; Cytokines/biosynthesis/genetics ; Female ; Gene Expression Regulation, Bacterial ; Humans ; *Immune Evasion ; Ixodes/microbiology ; Lipoproteins/genetics/*physiology ; Lyme Disease/immunology/microbiology ; Membrane Proteins/genetics/*physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C3H ; Mice, SCID ; Specific Pathogen-Free Organisms ; Virulence ; }, abstract = {Borrelia burgdorferi is one of the few extracellular pathogens capable of establishing persistent infection in mammals. The mechanisms that sustain long-term survival of this bacterium are largely unknown. Here we report a unique innate immune evasion strategy of B. burgdorferi, orchestrated by a surface protein annotated as BBA57, through its modulation of multiple spirochete virulent determinants. BBA57 function is critical for early infection but largely redundant for later stages of spirochetal persistence, either in mammals or in ticks. The protein influences host IFN responses as well as suppresses multiple host microbicidal activities involving serum complement, neutrophils, and antimicrobial peptides. We also discovered a remarkable plasticity in BBA57-mediated spirochete immune evasion strategy because its loss, although resulting in near clearance of pathogens at the inoculum site, triggers nonheritable adaptive changes that exclude detectable nucleotide alterations in the genome but incorporate transcriptional reprograming events. Understanding the malleability in spirochetal immune evasion mechanisms that ensures their host persistence is critical for the development of novel therapeutic and preventive approaches to combat long-term infections like Lyme borreliosis.}, } @article {pmid29610316, year = {2018}, author = {Mei, L and Fan, Y and Lv, X and Welsh, DK and Zhan, C and Zhang, EE}, title = {Long-term in vivo recording of circadian rhythms in brains of freely moving mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4276-4281}, pmid = {29610316}, issn = {1091-6490}, support = {I01 BX001146/BX/BLRD VA/United States ; }, mesh = {Animals ; Bacterial Proteins/analysis/genetics ; CA1 Region, Hippocampal/metabolism ; CA2 Region, Hippocampal/metabolism ; Cells, Cultured ; Circadian Rhythm/genetics/*physiology ; Cryptochromes/*biosynthesis/deficiency/genetics ; Dependovirus/genetics ; Fiber Optic Technology/instrumentation/*methods ; Fluorometry/instrumentation/*methods ; Genes, Reporter ; Genetic Vectors/administration & dosage/genetics ; Hypothalamus, Anterior/metabolism ; Longitudinal Studies ; Luminescent Proteins/analysis/genetics ; Mice ; Mice, Inbred C57BL ; Movement ; Neurons/chemistry/classification/*metabolism ; Optical Fibers ; Organ Specificity ; Period Circadian Proteins/*biosynthesis/genetics ; Photoperiod ; Suprachiasmatic Nucleus/cytology/*metabolism ; Transcription, Genetic ; Vasoactive Intestinal Peptide/analysis ; }, abstract = {Endogenous circadian clocks control 24-h physiological and behavioral rhythms in mammals. Here, we report a real-time in vivo fluorescence recording system that enables long-term monitoring of circadian rhythms in the brains of freely moving mice. With a designed reporter of circadian clock gene expression, we tracked robust Cry1 transcription reporter rhythms in the suprachiasmatic nucleus (SCN) of WT, Cry1-/- , and Cry2-/- mice in LD (12 h light, 12 h dark) and DD (constant darkness) conditions and verified that signals remained stable for over 6 mo. Further, we recorded Cry1 transcriptional rhythms in the subparaventricular zone (SPZ) and hippocampal CA1/2 regions of WT mice housed under LD and DD conditions. By using a Cre-loxP system, we recorded Per2 and Cry1 transcription rhythms specifically in vasoactive intestinal peptide (VIP) neurons of the SCN. Finally, we demonstrated the dynamics of Per2 and Cry1 transcriptional rhythms in SCN VIP neurons following an 8-h phase advance in the light/dark cycle.}, } @article {pmid29610315, year = {2018}, author = {}, title = {Correction for Ramus et al,. An invasive foundation species enhances multifunctionality in a coastal ecosystem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3856}, doi = {10.1073/pnas.1804651115}, pmid = {29610315}, issn = {1091-6490}, } @article {pmid29610314, year = {2018}, author = {Bocci, F and Suzuki, Y and Lu, M and Onuchic, JN}, title = {Role of metabolic spatiotemporal dynamics in regulating biofilm colony expansion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4288-4293}, pmid = {29610314}, issn = {1091-6490}, support = {P30 CA034196/CA/NCI NIH HHS/United States ; }, mesh = {Ammonium Compounds/metabolism ; Bacillus subtilis/cytology/drug effects/*growth & development/metabolism ; Bacterial Proteins/metabolism ; Biofilms/*growth & development ; Bioreactors ; Diffusion ; Enzyme Activation/drug effects ; Glutamate Dehydrogenase/metabolism ; Glutamic Acid/metabolism/pharmacology ; Glutamine/biosynthesis ; Lab-On-A-Chip Devices ; Time Factors ; }, abstract = {Cell fate determination is typically regulated by biological networks, yet increasing evidences suggest that cell-cell communication and environmental stresses play crucial roles in the behavior of a cell population. A recent microfluidic experiment showed that the metabolic codependence of two cell populations generates a collective oscillatory dynamic during the expansion of a Bacillus subtilis biofilm. We develop a modeling framework for the spatiotemporal dynamics of the associated metabolic circuit for cells in a colony. We elucidate the role of metabolite diffusion and the need of two distinct cell populations to observe oscillations. Uniquely, this description captures the onset and thereafter stable oscillatory dynamics during expansion and predicts the existence of damping oscillations under various environmental conditions. This modeling scheme provides insights to understand how cells integrate the information from external signaling and cell-cell communication to determine the optimal survival strategy and/or maximize cell fitness in a multicellular system.}, } @article {pmid29610313, year = {2018}, author = {Krissansen-Totton, J and Arney, GN and Catling, DC}, title = {Constraining the climate and ocean pH of the early Earth with a geological carbon cycle model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4105-4110}, pmid = {29610313}, issn = {1091-6490}, abstract = {The early Earth's environment is controversial. Climatic estimates range from hot to glacial, and inferred marine pH spans strongly alkaline to acidic. Better understanding of early climate and ocean chemistry would improve our knowledge of the origin of life and its coevolution with the environment. Here, we use a geological carbon cycle model with ocean chemistry to calculate self-consistent histories of climate and ocean pH. Our carbon cycle model includes an empirically justified temperature and pH dependence of seafloor weathering, allowing the relative importance of continental and seafloor weathering to be evaluated. We find that the Archean climate was likely temperate (0-50 °C) due to the combined negative feedbacks of continental and seafloor weathering. Ocean pH evolves monotonically from [Formula: see text] (2σ) at 4.0 Ga to [Formula: see text] (2σ) at the Archean-Proterozoic boundary, and to [Formula: see text] (2σ) at the Proterozoic-Phanerozoic boundary. This evolution is driven by the secular decline of pCO2, which in turn is a consequence of increasing solar luminosity, but is moderated by carbonate alkalinity delivered from continental and seafloor weathering. Archean seafloor weathering may have been a comparable carbon sink to continental weathering, but is less dominant than previously assumed, and would not have induced global glaciation. We show how these conclusions are robust to a wide range of scenarios for continental growth, internal heat flow evolution and outgassing history, greenhouse gas abundances, and changes in the biotic enhancement of weathering.}, } @article {pmid29610312, year = {2018}, author = {Lee, AJ and Wang, S and Meredith, HR and Zhuang, B and Dai, Z and You, L}, title = {Robust, linear correlations between growth rates and β-lactam-mediated lysis rates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4069-4074}, pmid = {29610312}, issn = {1091-6490}, support = {R01 GM098642/GM/NIGMS NIH HHS/United States ; R01 GM110494/GM/NIGMS NIH HHS/United States ; R24 DK110492/DK/NIDDK NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Load ; Bacteriolysis/*drug effects ; Biomass ; Carbenicillin/*pharmacology ; Culture Media/pharmacology ; Escherichia coli/*drug effects/growth & development ; High-Throughput Screening Assays/instrumentation ; Kinetics ; Nephelometry and Turbidimetry ; Robotics ; Temperature ; }, abstract = {It is widely acknowledged that faster-growing bacteria are killed faster by β-lactam antibiotics. This notion serves as the foundation for the concept of bacterial persistence: dormant bacterial cells that do not grow are phenotypically tolerant against β-lactam treatment. Such correlation has often been invoked in the mathematical modeling of bacterial responses to antibiotics. Due to the lack of thorough quantification, however, it is unclear whether and to what extent the bacterial growth rate can predict the lysis rate upon β-lactam treatment under diverse conditions. Enabled by experimental automation, here we measured >1,000 growth/killing curves for eight combinations of antibiotics and bacterial species and strains, including clinical isolates of bacterial pathogens. We found that the lysis rate of a bacterial population linearly depends on the instantaneous growth rate of the population, regardless of how the latter is modulated. We further demonstrate that this predictive power at the population level can be explained by accounting for bacterial responses to the antibiotic treatment by single cells. This linear dependence of the lysis rate on the growth rate represents a dynamic signature associated with each bacterium-antibiotic pair and serves as the quantitative foundation for designing combination antibiotic therapy and predicting the population-structure change in a population with mixed phenotypes.}, } @article {pmid29610311, year = {2018}, author = {}, title = {Correction for Jiang et al., Proteins induced by telomere dysfunction and DNA damage represent biomarkers of human aging and disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3600}, doi = {10.1073/pnas.1804185115}, pmid = {29610311}, issn = {1091-6490}, } @article {pmid29610310, year = {2018}, author = {Friedman, ES and Bittinger, K and Esipova, TV and Hou, L and Chau, L and Jiang, J and Mesaros, C and Lund, PJ and Liang, X and FitzGerald, GA and Goulian, M and Lee, D and Garcia, BA and Blair, IA and Vinogradov, SA and Wu, GD}, title = {Microbes vs. chemistry in the origin of the anaerobic gut lumen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4170-4175}, pmid = {29610310}, issn = {1091-6490}, support = {R01 EB018464/EB/NIBIB NIH HHS/United States ; R24 NS092986/NS/NINDS NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; T32 CA009140/CA/NCI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; P42 ES023720/ES/NIEHS NIH HHS/United States ; R01 GM080279/GM/NIGMS NIH HHS/United States ; R01 AI118891/AI/NIAID NIH HHS/United States ; R01 GM103591/GM/NIGMS NIH HHS/United States ; }, mesh = {*Anaerobiosis ; Animals ; Bacteria, Anaerobic/isolation & purification/*metabolism ; Computer Systems ; Gastric Mucosa/metabolism ; Gastrointestinal Contents/chemistry ; *Gastrointestinal Microbiome ; Germ-Free Life ; Intestinal Mucosa/*metabolism ; Lipids/chemistry ; Luminescent Measurements ; Metalloporphyrins/analysis ; Mice ; Mice, Inbred C57BL ; Oxidation-Reduction ; Oxygen/analysis/*metabolism ; Oxygen Consumption ; Proteins/chemistry ; }, abstract = {The succession from aerobic and facultative anaerobic bacteria to obligate anaerobes in the infant gut along with the differences between the compositions of the mucosally adherent vs. luminal microbiota suggests that the gut microbes consume oxygen, which diffuses into the lumen from the intestinal tissue, maintaining the lumen in a deeply anaerobic state. Remarkably, measurements of luminal oxygen levels show nearly identical pO2 (partial pressure of oxygen) profiles in conventional and germ-free mice, pointing to the existence of oxygen consumption mechanisms other than microbial respiration. In vitro experiments confirmed that the luminal contents of germ-free mice are able to chemically consume oxygen (e.g., via lipid oxidation reactions), although at rates significantly lower than those observed in the case of conventionally housed mice. For conventional mice, we also show that the taxonomic composition of the gut microbiota adherent to the gut mucosa and in the lumen throughout the length of the gut correlates with oxygen levels. At the same time, an increase in the biomass of the gut microbiota provides an explanation for the reduction of luminal oxygen in the distal vs. proximal gut. These results demonstrate how oxygen from the mammalian host is used by the gut microbiota, while both the microbes and the oxidative chemical reactions regulate luminal oxygen levels, shaping the composition of the microbial community throughout different regions of the gut.}, } @article {pmid29610309, year = {2018}, author = {Kozma, EE and Webb, NM and Harcourt-Smith, WEH and Raichlen, DA and D'Août, K and Brown, MH and Finestone, EM and Ross, SR and Aerts, P and Pontzer, H}, title = {Hip extensor mechanics and the evolution of walking and climbing capabilities in humans, apes, and fossil hominins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4134-4139}, pmid = {29610309}, issn = {1091-6490}, mesh = {Adult ; Anatomy, Comparative ; Animals ; Anthropometry ; Biological Evolution ; Biomechanical Phenomena ; Fossils ; Gait/*physiology ; Hamstring Muscles/*physiology ; Hip/*physiology ; Hominidae/anatomy & histology/*physiology ; Humans ; Hylobatidae/anatomy & histology/physiology ; Male ; Pelvis/physiology ; Posture ; Range of Motion, Articular ; Walking/physiology ; }, abstract = {The evolutionary emergence of humans' remarkably economical walking gait remains a focus of research and debate, but experimentally validated approaches linking locomotor capability to postcranial anatomy are limited. In this study, we integrated 3D morphometrics of hominoid pelvic shape with experimental measurements of hip kinematics and kinetics during walking and climbing, hamstring activity, and passive range of hip extension in humans, apes, and other primates to assess arboreal-terrestrial trade-offs in ischium morphology among living taxa. We show that hamstring-powered hip extension during habitual walking and climbing in living apes and humans is strongly predicted, and likely constrained, by the relative length and orientation of the ischium. Ape pelves permit greater extensor moments at the hip, enhancing climbing capability, but limit their range of hip extension, resulting in a crouched gait. Human pelves reduce hip extensor moments but permit a greater degree of hip extension, which greatly improves walking economy (i.e., distance traveled/energy consumed). Applying these results to fossil pelves suggests that early hominins differed from both humans and extant apes in having an economical walking gait without sacrificing climbing capability. Ardipithecus was capable of nearly human-like hip extension during bipedal walking, but retained the capacity for powerful, ape-like hip extension during vertical climbing. Hip extension capability was essentially human-like in Australopithecus afarensis and Australopithecus africanus, suggesting an economical walking gait but reduced mechanical advantage for powered hip extension during climbing.}, } @article {pmid29610308, year = {2018}, author = {Vega-Rubín-de-Celis, S and Zou, Z and Fernández, ÁF and Ci, B and Kim, M and Xiao, G and Xie, Y and Levine, B}, title = {Increased autophagy blocks HER2-mediated breast tumorigenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4176-4181}, pmid = {29610308}, issn = {1091-6490}, support = {R01 CA109618/CA/NCI NIH HHS/United States ; R01 CA172211/CA/NCI NIH HHS/United States ; R01 GM115473/GM/NIGMS NIH HHS/United States ; R01 CA109618/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; *Autophagy/drug effects ; Beclin-1/deficiency/genetics/*physiology ; Breast Neoplasms/pathology ; Cell Line, Tumor ; Female ; Gene Knock-In Techniques ; Humans ; Lapatinib ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Molecular Targeted Therapy ; Mutation ; Neoplasm Proteins/deficiency/genetics/*physiology ; Peptide Fragments/therapeutic use ; Protein Binding/drug effects ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Quinazolines/pharmacology ; Random Allocation ; Receptor, ErbB-2/antagonists & inhibitors/*physiology ; Xenograft Model Antitumor Assays ; }, abstract = {Allelic loss of the autophagy gene, beclin 1/BECN1, increases the risk of patients developing aggressive, including human epidermal growth factor receptor 2 (HER2)-positive, breast cancers; however, it is not known whether autophagy induction may be beneficial in preventing HER2-positive breast tumor growth. We explored the regulation of autophagy in breast cancer cells by HER2 in vitro and the effects of genetic and pharmacological strategies to increase autophagy on HER2-driven breast cancer growth in vivo. Our findings demonstrate that HER2 interacts with Beclin 1 in breast cancer cells and inhibits autophagy. Mice with increased basal autophagy due to a genetically engineered mutation in Becn1 are protected from HER2-driven mammary tumorigenesis, and HER2 fails to inhibit autophagy in primary cells derived from these mice. Moreover, treatment of mice with HER2-positive human breast cancer xenografts with the Tat-Beclin 1 autophagy-inducing peptide inhibits tumor growth as effectively as a clinically used HER2 tyrosine kinase inhibitor (TKI). This inhibition of tumor growth is associated with a robust induction of autophagy, a disruption of HER2/Beclin 1 binding, and a transcriptional signature in the tumors distinct from that observed with HER2 TKI treatment. Taken together, these findings indicate that the HER2-mediated inhibition of Beclin 1 and autophagy likely contributes to HER2-mediated tumorigenesis and that strategies to block HER2/Beclin 1 binding and/or increase autophagy may represent a new therapeutic approach for HER2-positive breast cancers.}, } @article {pmid29610307, year = {2018}, author = {Li, Y and Li, S and Thodey, K and Trenchard, I and Cravens, A and Smolke, CD}, title = {Complete biosynthesis of noscapine and halogenated alkaloids in yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E3922-E3931}, pmid = {29610307}, issn = {1091-6490}, support = {DP1 AT007886/AT/NCCIH NIH HHS/United States ; }, mesh = {Hydrocarbons, Halogenated/*metabolism ; *Metabolic Engineering ; Noscapine/*metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; }, abstract = {Microbial biosynthesis of plant natural products from simple building blocks is a promising approach toward scalable production and modification of high-value compounds. The pathway for biosynthesis of noscapine, a potential anticancer compound, from canadine was recently elucidated as a 10-gene cluster from opium poppy. Here we demonstrate the de novo production of noscapine in Saccharomyces cerevisiae, through the reconstruction of a biosynthetic pathway comprising over 30 enzymes from plants, bacteria, mammals, and yeast itself, including 7 plant endoplasmic reticulum (ER)-localized enzymes. Optimization directed to tuning expression of pathway enzymes, host endogenous metabolic pathways, and fermentation conditions led to an over 18,000-fold improvement from initial noscapine titers to ∼2.2 mg/L. By feeding modified tyrosine derivatives to the optimized noscapine-producing strain we further demonstrated microbial production of halogenated benzylisoquinoline alkaloids. This work highlights the potential for microbial biosynthetic platforms to support the synthesis of valuable and novel alkaloid compounds, which can advance alkaloid-based drug discovery and development.}, } @article {pmid29610306, year = {2018}, author = {McBrayer, SK and Olenchock, BA and DiNatale, GJ and Shi, DD and Khanal, J and Jennings, RB and Novak, JS and Oser, MG and Robbins, AK and Modiste, R and Bonal, D and Moslehi, J and Bronson, RT and Neuberg, D and Nguyen, QD and Signoretti, S and Losman, JA and Kaelin, WG}, title = {Autochthonous tumors driven by Rb1 loss have an ongoing requirement for the RBP2 histone demethylase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3741-E3748}, pmid = {29610306}, issn = {1091-6490}, support = {R35 CA210068/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Alleles ; Animals ; DNA-Binding Proteins/deficiency/genetics/*physiology ; Echocardiography ; Enzyme Activation/drug effects ; Fibroblasts ; Genes, Retinoblastoma ; Heart Septal Defects/genetics ; Histone Code/drug effects/*physiology ; Integrases/drug effects ; Jumonji Domain-Containing Histone Demethylases/deficiency/genetics/*physiology ; Mice ; Mice, Inbred C57BL ; Molecular Targeted Therapy/*methods ; Neoplasm Proteins/*physiology ; Pituitary Neoplasms/*enzymology/genetics/therapy ; Recombinant Fusion Proteins/biosynthesis/genetics ; Retinoblastoma Protein/*deficiency ; Tamoxifen/pharmacology ; Thyroid Neoplasms/*enzymology/genetics/therapy ; Transgenes/drug effects ; }, abstract = {Inactivation of the retinoblastoma gene (RB1) product, pRB, is common in many human cancers. Targeting downstream effectors of pRB that are central to tumorigenesis is a promising strategy to block the growth of tumors harboring loss-of-function RB1 mutations. One such effector is retinoblastoma-binding protein 2 (RBP2, also called JARID1A or KDM5A), which encodes an H3K4 demethylase. Binding of pRB to RBP2 has been linked to the ability of pRB to promote senescence and differentiation. Importantly, genetic ablation of RBP2 is sufficient to phenocopy pRB's ability to induce these cellular changes in cell culture experiments. Moreover, germline Rbp2 deletion significantly impedes tumorigenesis in Rb1+/- mice. The value of RBP2 as a therapeutic target in cancer, however, hinges on whether loss of RBP2 could block the growth of established tumors as opposed to simply delaying their onset. Here we show that conditional, systemic ablation of RBP2 in tumor-bearing Rb1+/- mice is sufficient to slow tumor growth and significantly extend survival without causing obvious toxicity to the host. These findings show that established Rb1-null tumors require RBP2 for growth and further credential RBP2 as a therapeutic target in human cancers driven by RB1 inactivation.}, } @article {pmid29610305, year = {2018}, author = {Ponzoni, L and Bahar, I}, title = {Structural dynamics is a determinant of the functional significance of missense variants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4164-4169}, pmid = {29610305}, issn = {1091-6490}, support = {P41 GM103712/GM/NIGMS NIH HHS/United States ; U54 HG008540/HG/NHGRI NIH HHS/United States ; }, mesh = {Allosteric Regulation ; Allosteric Site ; Amino Acid Sequence ; *Amino Acid Substitution ; Base Sequence ; Computational Biology ; Conserved Sequence ; Cystic Fibrosis/genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/chemistry/genetics ; Datasets as Topic ; Genetic Association Studies ; Humans ; Models, Chemical ; *Mutation, Missense ; *Protein Conformation ; Structure-Activity Relationship ; }, abstract = {Accurate evaluation of the effect of point mutations on protein function is essential to assessing the genesis and prognosis of many inherited diseases and cancer types. Currently, a wealth of computational tools has been developed for pathogenicity prediction. Two major types of data are used to this aim: sequence conservation/evolution and structural properties. Here, we demonstrate in a systematic way that another determinant of the functional impact of missense variants is the protein's structural dynamics. Measurable improvement is shown in pathogenicity prediction by taking into consideration the dynamical context and implications of the mutation. Our study suggests that the class of dynamics descriptors introduced here may be used in conjunction with existing features to not only increase the prediction accuracy of the impact of variants on biological function, but also gain insight into the physical basis of the effect of missense variants.}, } @article {pmid29610304, year = {2018}, author = {Snyder, BER and Böttger, LH and Bols, ML and Yan, JJ and Rhoda, HM and Jacobs, AB and Hu, MY and Zhao, J and Alp, EE and Hedman, B and Hodgson, KO and Schoonheydt, RA and Sels, BF and Solomon, EI}, title = {Structural characterization of a non-heme iron active site in zeolites that hydroxylates methane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4565-4570}, pmid = {29610304}, issn = {1091-6490}, support = {P41 GM103393/GM/NIGMS NIH HHS/United States ; }, mesh = {Catalysis ; Catalytic Domain ; Hydroxylation/physiology ; Iron/*chemistry/metabolism ; Methane/chemistry/metabolism ; Methanol/chemistry ; Models, Molecular ; Molecular Structure ; Oxygen/chemistry ; Spectrophotometry/methods ; Zeolites/*chemistry/*metabolism ; }, abstract = {Iron-containing zeolites exhibit unprecedented reactivity in the low-temperature hydroxylation of methane to form methanol. Reactivity occurs at a mononuclear ferrous active site, α-Fe(II), that is activated by N2O to form the reactive intermediate α-O. This has been defined as an Fe(IV)=O species. Using nuclear resonance vibrational spectroscopy coupled to X-ray absorption spectroscopy, we probe the bonding interaction between the iron center, its zeolite lattice-derived ligands, and the reactive oxygen. α-O is found to contain an unusually strong Fe(IV)=O bond resulting from a constrained coordination geometry enforced by the zeolite lattice. Density functional theory calculations clarify how the experimentally determined geometric structure of the active site leads to an electronic structure that is highly activated to perform H-atom abstraction.}, } @article {pmid29610303, year = {2018}, author = {Jubin, L and Poggioli, A and Siria, A and Bocquet, L}, title = {Dramatic pressure-sensitive ion conduction in conical nanopores.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4063-4068}, pmid = {29610303}, issn = {1091-6490}, support = {637748//European Research Council/International ; }, mesh = {*Electric Conductivity ; Equipment Design ; Glass ; *Ions ; Models, Chemical ; *Nanopores ; *Pressure ; Static Electricity ; Stress, Mechanical ; }, abstract = {Ion transporters in Nature exhibit a wealth of complex transport properties such as voltage gating, activation, and mechanosensitive behavior. When combined, such processes result in advanced ionic machines achieving active ion transport, high selectivity, or signal processing. On the artificial side, there has been much recent progress in the design and study of transport in ionic channels, but mimicking the advanced functionalities of ion transporters remains as yet out of reach. A prerequisite is the development of ionic responses sensitive to external stimuli. In the present work, we report a counterintuitive and highly nonlinear coupling between electric and pressure-driven transport in a conical nanopore, manifesting as a strong pressure dependence of the ionic conductance. This result is at odds with standard linear response theory and is akin to a mechanical transistor functionality. We fully rationalize this behavior on the basis of the coupled electrohydrodynamics in the conical pore by extending the Poisson-Nernst-Planck-Stokes framework. The model is shown to capture the subtle mechanical balance occurring within an extended spatially charged zone in the nanopore. The pronounced sensitivity to mechanical forcing offers leads in tuning ion transport by mechanical stimuli. The results presented here provide a promising avenue for the design of tailored membrane functionalities.}, } @article {pmid29610302, year = {2018}, author = {Heo, S and Diering, GH and Na, CH and Nirujogi, RS and Bachman, JL and Pandey, A and Huganir, RL}, title = {Identification of long-lived synaptic proteins by proteomic analysis of synaptosome protein turnover.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3827-E3836}, pmid = {29610302}, issn = {1091-6490}, support = {R01 CA184165/CA/NCI NIH HHS/United States ; R01 NS036715/NS/NINDS NIH HHS/United States ; S10 OD021844/OD/NIH HHS/United States ; P50 NS038377/NS/NINDS NIH HHS/United States ; P50 MH100024/MH/NIMH NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Animals ; Cytosol/metabolism ; Half-Life ; Learning/physiology ; Mass Spectrometry ; Memory/*physiology ; Mice ; Neuronal Plasticity ; Proteins/metabolism ; Proteolysis ; Proteomics/methods ; Synapses/*metabolism ; Synaptosomes/*metabolism ; }, abstract = {Memory formation is believed to result from changes in synapse strength and structure. While memories may persist for the lifetime of an organism, the proteins and lipids that make up synapses undergo constant turnover with lifetimes from minutes to days. The molecular basis for memory maintenance may rely on a subset of long-lived proteins (LLPs). While it is known that LLPs exist, whether such proteins are present at synapses is unknown. We performed an unbiased screen using metabolic pulse-chase labeling in vivo in mice and in vitro in cultured neurons combined with quantitative proteomics. We identified synaptic LLPs with half-lives of several months or longer. Proteins in synaptic fractions generally exhibited longer lifetimes than proteins in cytosolic fractions. Protein turnover was sensitive to pharmacological manipulations of activity in neuronal cultures or in mice exposed to an enriched environment. We show that synapses contain LLPs that may underlie stabile long-lasting changes in synaptic structure and function.}, } @article {pmid29610301, year = {2018}, author = {Gulley, AL and Nassar, NT and Xun, S}, title = {China, the United States, and competition for resources that enable emerging technologies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4111-4115}, pmid = {29610301}, issn = {1091-6490}, abstract = {Historically, resource conflicts have often centered on fuel minerals (particularly oil). Future resource conflicts may, however, focus more on competition for nonfuel minerals that enable emerging technologies. Whether it is rhenium in jet engines, indium in flat panel displays, or gallium in smart phones, obscure elements empower smarter, smaller, and faster technologies, and nations seek stable supplies of these and other nonfuel minerals for their industries. No nation has all of the resources it needs domestically. International trade may lead to international competition for these resources if supplies are deemed at risk or insufficient to satisfy growing demand, especially for minerals used in technologies important to economic development and national security. Here, we compare the net import reliance of China and the United States to inform mineral resource competition and foreign supply risk. Our analysis indicates that China relies on imports for over half of its consumption for 19 of 42 nonfuel minerals, compared with 24 for the United States-11 of which are common to both. It is for these 11 nonfuel minerals that competition between the United States and China may become the most contentious, especially for those with highly concentrated production that prove irreplaceable in pivotal emerging technologies.}, } @article {pmid29610300, year = {2018}, author = {}, title = {Correction for Bevan et al., Holocene fluctuations in human population demonstrate repeated links to food production and climate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3597}, doi = {10.1073/pnas.1804206115}, pmid = {29610300}, issn = {1091-6490}, } @article {pmid29610299, year = {2018}, author = {Liao, CC and Reed, JL and Qi, HX and Sawyer, EK and Kaas, JH}, title = {Second-order spinal cord pathway contributes to cortical responses after long recoveries from dorsal column injury in squirrel monkeys.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4258-4263}, pmid = {29610299}, issn = {1091-6490}, support = {R01 NS016446/NS/NINDS NIH HHS/United States ; R01 NS067017/NS/NINDS NIH HHS/United States ; }, mesh = {Afferent Pathways/physiopathology ; Animals ; Axonal Transport ; Axons/physiology ; Cholera Toxin/pharmacokinetics ; Convalescence ; Hand/innervation/*physiopathology ; Hypesthesia/physiopathology ; Medulla Oblongata/physiopathology ; Neuronal Plasticity/physiology ; Posterior Horn Cells/*physiology ; Recovery of Function/physiology ; Saimiri ; Somatosensory Cortex/*physiopathology ; Spinal Cord Injuries/*physiopathology ; Thalamus/physiopathology ; Touch Perception/*physiology ; }, abstract = {Months after the occurrence of spinal cord dorsal column lesions (DCLs) at the cervical level, neural responses in the hand representation of somatosensory area 3b hand cortex recover, along with hand use. To examine whether the second-order spinal cord pathway contributes to this functional recovery, we injected cholera toxin subunit B (CTB) into the hand representation in the cuneate nucleus (Cu) to label the spinal cord neurons, and related results to cortical reactivation in four squirrel monkeys (Saimiri boliviensis) at least 7 months after DCL. In two monkeys with complete DCLs, few CTB-labeled neurons were present below the lesion, and few neurons in the affected hand region in area 3b responded to touch on the hand. In two other cases with large but incomplete DCLs, CTB-labeled neurons were abundant below the lesion, and the area 3b hand cortex responded well to tactile stimulation in a roughly somatotopic organization. The proportions of labeled neurons in the spinal cord hand region reflected the extent of cortical reactivation to the hand. Comparing monkeys with short and long recovery times suggests that the numbers of labeled neurons below the lesion increase with time following incomplete DCLs (<95%) but decrease with time after nearly complete DCLs (≥95%). Taken together, these results suggest that the second-order spinal cord pathway facilitates cortical reactivation, likely through the potentiation of persisting tactile inputs from the hand to the Cu over months of postlesion recovery.}, } @article {pmid29610298, year = {2018}, author = {Loerakker, S and Stassen, OMJA and Ter Huurne, FM and Boareto, M and Bouten, CVC and Sahlgren, CM}, title = {Mechanosensitivity of Jagged-Notch signaling can induce a switch-type behavior in vascular homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3682-E3691}, pmid = {29610298}, issn = {1091-6490}, mesh = {Aged ; Arteries/ultrastructure ; Basic Helix-Loop-Helix Transcription Factors/biosynthesis/genetics ; Cell Cycle Proteins/biosynthesis/genetics ; Computer Simulation ; Endothelial Cells/metabolism ; Gene Expression Regulation ; Homeostasis ; Humans ; Jagged-1 Protein/biosynthesis/genetics/*physiology ; Ligands ; Mechanotransduction, Cellular/*physiology ; Middle Aged ; Models, Biological ; Morphogenesis/physiology ; Muscle Contraction/*physiology ; Muscle, Smooth, Vascular/*cytology/ultrastructure ; Myocytes, Smooth Muscle/*physiology ; Receptor, Notch3/biosynthesis/genetics/*physiology ; Repressor Proteins/biosynthesis/genetics ; Stress, Mechanical ; Transcription Factor HES-1/biosynthesis/genetics ; Video Recording ; }, abstract = {Hemodynamic forces and Notch signaling are both known as key regulators of arterial remodeling and homeostasis. However, how these two factors integrate in vascular morphogenesis and homeostasis is unclear. Here, we combined experiments and modeling to evaluate the impact of the integration of mechanics and Notch signaling on vascular homeostasis. Vascular smooth muscle cells (VSMCs) were cyclically stretched on flexible membranes, as quantified via video tracking, demonstrating that the expression of Jagged1, Notch3, and target genes was down-regulated with strain. The data were incorporated in a computational framework of Notch signaling in the vascular wall, where the mechanical load was defined by the vascular geometry and blood pressure. Upon increasing wall thickness, the model predicted a switch-type behavior of the Notch signaling state with a steep transition of synthetic toward contractile VSMCs at a certain transition thickness. These thicknesses varied per investigated arterial location and were in good agreement with human anatomical data, thereby suggesting that the Notch response to hemodynamics plays an important role in the establishment of vascular homeostasis.}, } @article {pmid29610297, year = {2018}, author = {Sznajder, ŁJ and Thomas, JD and Carrell, EM and Reid, T and McFarland, KN and Cleary, JD and Oliveira, R and Nutter, CA and Bhatt, K and Sobczak, K and Ashizawa, T and Thornton, CA and Ranum, LPW and Swanson, MS}, title = {Intron retention induced by microsatellite expansions as a disease biomarker.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4234-4239}, pmid = {29610297}, issn = {1091-6490}, support = {R37 NS040389/NS/NINDS NIH HHS/United States ; P50 NS048843/NS/NINDS NIH HHS/United States ; R01 NS040389/NS/NINDS NIH HHS/United States ; R01 NS083564/NS/NINDS NIH HHS/United States ; P01 NS058901/NS/NINDS NIH HHS/United States ; R01 NS098819/NS/NINDS NIH HHS/United States ; U54 NS048843/NS/NINDS NIH HHS/United States ; }, mesh = {Amyotrophic Lateral Sclerosis/*genetics ; Base Composition ; Biomarkers ; DNA Repeat Expansion/*genetics ; Frontotemporal Dementia/*genetics ; Fuchs' Endothelial Dystrophy/*genetics ; Humans ; Introns/*genetics ; Lymphocytes/chemistry ; Muscle, Skeletal/chemistry ; Myocardium/chemistry ; Myotonic Dystrophy/*genetics ; Organ Specificity ; Polymorphism, Single Nucleotide ; RNA Splicing ; RNA-Binding Proteins/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Sensitivity and Specificity ; Tissue Array Analysis ; }, abstract = {Expansions of simple sequence repeats, or microsatellites, have been linked to ∼30 neurological-neuromuscular diseases. While these expansions occur in coding and noncoding regions, microsatellite sequence and repeat length diversity is more prominent in introns with eight different trinucleotide to hexanucleotide repeats, causing hereditary diseases such as myotonic dystrophy type 2 (DM2), Fuchs endothelial corneal dystrophy (FECD), and C9orf72 amyotrophic lateral sclerosis and frontotemporal dementia (C9-ALS/FTD). Here, we test the hypothesis that these GC-rich intronic microsatellite expansions selectively trigger host intron retention (IR). Using DM2, FECD, and C9-ALS/FTD as examples, we demonstrate that retention is readily detectable in affected tissues and peripheral blood lymphocytes and conclude that IR screening constitutes a rapid and inexpensive biomarker for intronic repeat expansion disease.}, } @article {pmid29610296, year = {2018}, author = {Edholm, ES and Banach, M and Hyoe Rhoo, K and Pavelka, MS and Robert, J}, title = {Distinct MHC class I-like interacting invariant T cell lineage at the forefront of mycobacterial immunity uncovered in Xenopus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4023-E4031}, pmid = {29610296}, issn = {1091-6490}, support = {F31 CA192664/CA/NCI NIH HHS/United States ; R24 AI059830/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Histocompatibility Antigens Class I/genetics/*immunology ; *Immunity, Cellular ; Larva/genetics/immunology ; Mycobacterium Infections, Nontuberculous/genetics/*immunology ; Mycobacterium marinum/*immunology ; Receptors, Antigen, T-Cell, alpha-beta/genetics/*immunology ; T-Lymphocytes/*immunology ; Xenopus Proteins/genetics/*immunology ; Xenopus laevis ; }, abstract = {The amphibian Xenopus laevis is to date the only species outside of mammals where a MHC class I-like (MHC-like) restricted innate-like (i) T cell subset (iVα6 T cells) reminiscent of CD1d-restricted iNKT cells has been identified and functionally characterized. This provides an attractive in vivo model to study the biological analogies and differences between mammalian iT cells and the evolutionarily antecedent Xenopus iT cell defense system. Here, we report the identification of a unique iT cell subset (Vα45-Jα1.14) requiring a distinct MHC-like molecule (mhc1b4.L or XNC4) for its development and function. We used two complementary reverse genetic approaches: RNA interference by transgenesis to impair expression of either XNC4 or the Vα45-Jα1.14 rearrangement, and CRISPR/Cas9-mediated disruption of the Jα1.14 gene segment. Both XNC4 deficiency that ablates iVα45T cell development and the direct disruption of the iVα45-Jα1.14 T cell receptor dramatically impairs tadpole resistance to Mycobacterium marinum (Mm) infection. The higher mortality of Mm-infected tadpoles deficient for iVα45T cells correlates with dysregulated expression responses of several immune genes. In contrast, iVα45-Jα1.14-deficient tadpoles remain fully competent against infection by the ranavirus FV3, which indicates a specialization of this unique iT cell subset toward mycobacterial rather than viral pathogens that involve iVα6 T cells. These data suggest that amphibians, which are evolutionarily separated from mammals by more than 350 My, have independently diversified a prominent and convergent immune surveillance system based on MHC-like interacting innate-like T cells.}, } @article {pmid29610295, year = {2018}, author = {Chen, S and Bonifati, S and Qin, Z and St Gelais, C and Kodigepalli, KM and Barrett, BS and Kim, SH and Antonucci, JM and Ladner, KJ and Buzovetsky, O and Knecht, KM and Xiong, Y and Yount, JS and Guttridge, DC and Santiago, ML and Wu, L}, title = {SAMHD1 suppresses innate immune responses to viral infections and inflammatory stimuli by inhibiting the NF-κB and interferon pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3798-E3807}, pmid = {29610295}, issn = {1091-6490}, support = {R01 AI116603/AI/NIAID NIH HHS/United States ; T32 GM007223/GM/NIGMS NIH HHS/United States ; R01 AI104483/AI/NIAID NIH HHS/United States ; T32 GM008283/GM/NIGMS NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; R01 AI120209/AI/NIAID NIH HHS/United States ; R01 AI102778/AI/NIAID NIH HHS/United States ; R01 GM128212/GM/NIGMS NIH HHS/United States ; R01 AI130110/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Down-Regulation ; Gene Expression Regulation/drug effects ; Gene Silencing ; HEK293 Cells ; HIV/physiology ; Humans ; I-kappa B Kinase/antagonists & inhibitors ; *Immunity, Innate ; Inflammation/*immunology ; Interferon Regulatory Factor-7/antagonists & inhibitors ; Interferon-alpha/*biosynthesis/genetics ; Macrophages/immunology/virology ; Male ; Mice ; NF-KappaB Inhibitor alpha/metabolism ; NF-kappa B/*metabolism ; Phosphorylation ; Protein Processing, Post-Translational ; Recombinant Proteins/immunology ; SAM Domain and HD Domain-Containing Protein 1/*physiology ; Sendai virus/physiology ; Signal Transduction/immunology ; THP-1 Cells ; Virus Diseases/*immunology ; }, abstract = {Sterile alpha motif and HD-domain-containing protein 1 (SAMHD1) blocks replication of retroviruses and certain DNA viruses by reducing the intracellular dNTP pool. SAMHD1 has been suggested to down-regulate IFN and inflammatory responses to viral infections, although the functions and mechanisms of SAMHD1 in modulating innate immunity remain unclear. Here, we show that SAMHD1 suppresses the innate immune responses to viral infections and inflammatory stimuli by inhibiting nuclear factor-κB (NF-κB) activation and type I interferon (IFN-I) induction. Compared with control cells, infection of SAMHD1-silenced human monocytic cells or primary macrophages with Sendai virus (SeV) or HIV-1, or treatment with inflammatory stimuli, induces significantly higher levels of NF-κB activation and IFN-I induction. Exogenous SAMHD1 expression in cells or SAMHD1 reconstitution in knockout cells suppresses NF-κB activation and IFN-I induction by SeV infection or inflammatory stimuli. Mechanistically, SAMHD1 inhibits NF-κB activation by interacting with NF-κB1/2 and reducing phosphorylation of the NF-κB inhibitory protein IκBα. SAMHD1 also interacts with the inhibitor-κB kinase ε (IKKε) and IFN regulatory factor 7 (IRF7), leading to the suppression of the IFN-I induction pathway by reducing IKKε-mediated IRF7 phosphorylation. Interactions of endogenous SAMHD1 with NF-κB and IFN-I pathway proteins were validated in human monocytic cells and primary macrophages. Comparing splenocytes from SAMHD1 knockout and heterozygous mice, we further confirmed SAMHD1-mediated suppression of NF-κB activation, suggesting an evolutionarily conserved property of SAMHD1. Our findings reveal functions of SAMHD1 in down-regulating innate immune responses to viral infections and inflammatory stimuli, highlighting the importance of SAMHD1 in modulating antiviral immunity.}, } @article {pmid29610294, year = {2018}, author = {Kirchhof, J and Petrakova, L and Brinkhoff, A and Benson, S and Schmidt, J and Unteroberdörster, M and Wilde, B and Kaptchuk, TJ and Witzke, O and Schedlowski, M}, title = {Learned immunosuppressive placebo responses in renal transplant patients.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4223-4227}, pmid = {29610294}, issn = {1091-6490}, mesh = {Administration, Oral ; Adult ; Affect ; Association ; Catecholamines/metabolism ; *Conditioning, Classical ; Cyclosporine/*administration & dosage ; Dose-Response Relationship, Drug ; Dose-Response Relationship, Immunologic ; Female ; Hemodynamics ; Humans ; Hydrocortisone/metabolism ; Immunosuppressive Agents/*administration & dosage ; Interferon-gamma Release Tests ; *Kidney Transplantation ; Learning ; *Lymphocyte Activation/drug effects ; Male ; Middle Aged ; *Placebo Effect ; Placebos ; Proof of Concept Study ; T-Lymphocyte Subsets/*immunology ; Tacrolimus/*administration & dosage ; Taste ; }, abstract = {Patients after organ transplantation or with chronic, inflammatory autoimmune diseases require lifelong treatment with immunosuppressive drugs, which have toxic adverse effects. Recent insight into the neurobiology of placebo responses shows that associative conditioning procedures can be employed as placebo-induced dose reduction strategies in an immunopharmacological regimen. However, it is unclear whether learned immune responses can be produced in patient populations already receiving an immunosuppressive regimen. Thus, 30 renal transplant patients underwent a taste-immune conditioning paradigm, in which immunosuppressive drugs (unconditioned stimulus) were paired with a gustatory stimulus [conditioned stimulus (CS)] during the learning phase. During evocation phase, after patients were reexposed to the CS, T cell proliferative capacity was significantly reduced in comparison with the baseline kinetics of T cell functions under routine drug intake (ƞp2 = 0.34). These data demonstrate, proof-of-concept, that learned immunosuppressive placebo responses can be used as a supportive, placebo-based, dose-reduction strategy to improve treatment efficacy in an ongoing immunopharmacological regimen.}, } @article {pmid29610293, year = {2018}, author = {Lemordant, L and Gentine, P and Swann, AS and Cook, BI and Scheff, J}, title = {Critical impact of vegetation physiology on the continental hydrologic cycle in response to increasing CO2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4093-4098}, pmid = {29610293}, issn = {1091-6490}, mesh = {*Atmosphere ; Biomass ; Carbon/metabolism ; *Carbon Cycle ; Carbon Dioxide/*pharmacology ; *Climate Change ; Droughts ; Plant Leaves/*drug effects/metabolism/radiation effects ; Plant Physiological Phenomena/*drug effects/radiation effects ; Plant Stomata/physiology ; Plant Transpiration/drug effects ; Sunlight ; Water/metabolism ; *Water Cycle ; }, abstract = {Predicting how increasing atmospheric CO2 will affect the hydrologic cycle is of utmost importance for a range of applications ranging from ecological services to human life and activities. A typical perspective is that hydrologic change is driven by precipitation and radiation changes due to climate change, and that the land surface will adjust. Using Earth system models with decoupled surface (vegetation physiology) and atmospheric (radiative) CO2 responses, we here show that the CO2 physiological response has a dominant role in evapotranspiration and evaporative fraction changes and has a major effect on long-term runoff compared with radiative or precipitation changes due to increased atmospheric CO2 This major effect is true for most hydrological stress variables over the largest fraction of the globe, except for soil moisture, which exhibits a more nonlinear response. This highlights the key role of vegetation in controlling future terrestrial hydrologic response and emphasizes that the carbon and water cycles are intimately coupled over land.}, } @article {pmid29610120, year = {2018}, author = {Dever, TE and Dinman, JD and Green, R}, title = {Translation Elongation and Recoding in Eukaryotes.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, pmid = {29610120}, issn = {1943-0264}, support = {R01 GM117177/GM/NIGMS NIH HHS/United States ; R01 HL119439/HL/NHLBI NIH HHS/United States ; R37 GM059425/GM/NIGMS NIH HHS/United States ; }, abstract = {In this review, we highlight the current understanding of translation elongation and recoding in eukaryotes. In addition to providing an overview of the process, recent advances in our understanding of the role of the factor eIF5A in both translation elongation and termination are discussed. We also highlight mechanisms of translation recoding with a focus on ribosomal frameshifting during elongation. We see that the balance between the basic steps in elongation and the less common recoding events is determined by the kinetics of the different processes as well as by specific sequence determinants.}, } @article {pmid29609907, year = {2018}, author = {Caves, EM and Brandley, NC and Johnsen, S}, title = {Visual Acuity and the Evolution of Signals.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {358-372}, doi = {10.1016/j.tree.2018.03.001}, pmid = {29609907}, issn = {1872-8383}, mesh = {*Animal Communication ; Animals ; *Biological Evolution ; Communication ; Humans ; *Life History Traits ; *Visual Acuity ; }, abstract = {Acuity, the fineness with which sensory systems perceive and parse information, limits the information that organisms can extract from stimuli. Here, we focus on visual acuity (the ability to perceive static spatial detail) to discuss relationships between acuity and signal form and evolution. Research suggests that acuity varies by orders of magnitude across species, and that most animals have much lower acuity than humans. Thus, hypotheses regarding the function of spatial patterns must account for the acuity of relevant viewers. New data quantifying acuity in a range of taxa allow us to examine correlations between acuity and ecology, elucidate the selective forces that receiver acuity places on signal evolution, and examine how signals might appear to viewers with different acuities.}, } @article {pmid29609778, year = {2018}, author = {Drayson, Z}, title = {The realizers and vehicles of mental representation.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {80-87}, doi = {10.1016/j.shpsa.2018.01.005}, pmid = {29609778}, issn = {0039-3681}, abstract = {The neural vehicles of mental representation play an explanatory role in cognitive psychology that their realizers do not. Cognitive psychology individuates neural structures as representational vehicles in terms of the specific causal properties to which cognitive mechanisms are sensitive. Explanations that appeal to properties of vehicles can capture generalisations which are not available at the level of their neural realizers. In this paper, I argue that the individuation of realizers as vehicles restricts the sorts of explanations in which they can participate. I illustrate this with reference to Rupert's (2011) claim that representational vehicles can play an explanatory role in psychology in virtue of their quantity or proportion. I propose that such quantity-based explanatory claims can apply only to realizers and not to vehicles, in virtue of the particular causal role that vehicles play in psychological explanations.}, } @article {pmid29609777, year = {2018}, author = {Kästner, L}, title = {Integrating mechanistic explanations through epistemic perspectives.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {68-79}, doi = {10.1016/j.shpsa.2018.01.011}, pmid = {29609777}, issn = {0039-3681}, abstract = {Talk of levels is ubiquitous in philosophy, especially in the context of mechanistic explanations spanning multiple levels. The mechanistic conception of levels, however, does not allow for the kind of integration needed to construct such multi-level mechanistic explanations integrating observations from different scientific domains. To address the issues arising in this context, I build on a certain perspectival aspect inherent in the mechanistic view. Rather than focusing on compositionally related levels of mechanisms, I suggest analyzing the situation in terms of epistemic perspectives researchers take when making scientific observations. Characterizing epistemic perspectives along five dimensions allows for a systematic analysis of the relations the scientific observations made from these different epistemic perspectives. This, in turn, provides a solid foundation for integrating the mechanistic explanations that are based on the scientific observations in question.}, } @article {pmid29609776, year = {2018}, author = {Krickel, B}, title = {Saving the mutual manipulability account of constitutive relevance.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {58-67}, doi = {10.1016/j.shpsa.2018.01.003}, pmid = {29609776}, issn = {0039-3681}, abstract = {Constitutive mechanistic explanations are said to refer to mechanisms that constitute the phenomenon-to-be-explained. The most prominent approach of how to understand this relation is Carl Craver's mutual manipulability approach (MM) to constitutive relevance. Recently, MM has come under attack (Baumgartner and Casini 2017; Baumgartner and Gebharter 2015; Harinen 2014; Kästner 2017; Leuridan 2012; Romero 2015). It is argued that MM is inconsistent because, roughly, it is spelled out in terms of interventionism (which is an approach to causation), whereas constitutive relevance is said to be a non-causal relation. In this paper, I will discuss a strategy of how to resolve this inconsistency-so-called fat-handedness approaches (Baumgartner and Casini 2017; Baumgartner and Gebharter 2015; Romero 2015). I will argue that these approaches are problematic. I will present a novel suggestion for how to consistently define constitutive relevance in terms of interventionism. My approach is based on a causal interpretation of manipulability in terms of causal relations between the mechanism's components and what I will call temporal EIO-parts of the phenomenon. Still, this interpretation accounts for the fundamental difference between constitutive relevance and causal relevance.}, } @article {pmid29609775, year = {2018}, author = {Polger, TW and Shapiro, LA and Stern, R}, title = {In defense of interventionist solutions to exclusion.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {51-57}, doi = {10.1016/j.shpsa.2018.01.012}, pmid = {29609775}, issn = {0039-3681}, } @article {pmid29609774, year = {2018}, author = {Huneman, P}, title = {Realizability and the varieties of explanation.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {37-50}, doi = {10.1016/j.shpsa.2018.01.004}, pmid = {29609774}, issn = {0039-3681}, abstract = {What realization is has been convincingly presented in relation to the way we determine what counts as the realizers of realized properties. The way we explain a fact of realization includes a reference to what realization should be; therefore it informs in turn our understanding of the nature of realization. Conceptions of explanation are thereby included in the views of realization as a metaphysical property. Recently, several major views of realization such as Polger and Shapiro's or Gillett and Aizawa's, however competing, have relied on the neo-mechanicist theory of explanations (e.g,. Darden and Caver 2013), currently popular among philosophers of science. However, it has also been increasingly argued that some explanations are not mechanistic (e.g., Batterman 2009). Using an account given in Huneman (2017), I argue that within those explanations the fact that some mathematical properties are instantiated is explanatory, and that this defines a specific explanatory type called "structural explanation", whose subtypes could be: optimality explanations (usually found in economics), topological explanations, etc. This paper thereby argues that all subtypes of structural explanation define several kinds of realizability, which are not equivalent to the usual notion of realization tied to mechanistic explanations, onto which many of the philosophical investigations are focused. Then it draws some consequences concerning the notion of multiple realizability.}, } @article {pmid29609773, year = {2018}, author = {Fuller, G}, title = {Physicalism, realization, and structure.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {31-36}, doi = {10.1016/j.shpsa.2017.11.006}, pmid = {29609773}, issn = {0039-3681}, abstract = {In the philosophy of mind and psychology, a central question since the 1960s has been that of how to give a philosophically adequate formulation of mind-body physicalism. A large quantity of work on the topic has been done in the interim. There have been, and continue to be, extensive discussions of the ideas of physicalism, identity, functionalism, realization, and constitution. My aim in this paper is a modest one: it is to get clearer about these ideas and some of their interrelations. After providing some background and history, I shall focus on two related topics: the distinction between a functional property and a structural one and the dispute over whether a realization account of the mental-physical relation provides a better physicalist account than a constitutional account.}, } @article {pmid29609772, year = {2018}, author = {Aizawa, K}, title = {Multiple realization and multiple "ways" of realization: A progress report.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {3-9}, doi = {10.1016/j.shpsa.2017.11.005}, pmid = {29609772}, issn = {0039-3681}, abstract = {One might have thought that if something has two or more distinct realizations, then that thing is multiply realized. Nevertheless, some philosophers have claimed that two or more distinct realizations do not amount to multiple realization, unless those distinct realizations amount to multiple "ways" of realizing the thing. Corey Maley, Gualtiero Piccinini, Thomas Polger, and Lawrence Shapiro are among these philosophers. Unfortunately, they do not explain why multiple realization requires multiple "ways" of realizing. More significantly, their efforts to articulate multiple "ways" of realizing turn out to be problematic.}, } @article {pmid29609771, year = {2018}, author = {Adams, F}, title = {Cognition wars.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {20-30}, doi = {10.1016/j.shpsa.2017.11.007}, pmid = {29609771}, issn = {0039-3681}, abstract = {In what kinds of physical systems can cognition be realized? There are currently competing answers among scientists and theorists of cognition. There are many plant scientists who maintain that cognition can be realized in plants. There are biological scientists who maintain that cognition is materially realized in bacteria. In this paper, I will present the basis for such claims and evaluate them and discuss the future for theories of the metaphysical basis of cognition in the cognitive sciences.}, } @article {pmid29609770, year = {2018}, author = {Shapiro, L}, title = {Reduction redux.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {10-19}, doi = {10.1016/j.shpsa.2017.11.004}, pmid = {29609770}, issn = {0039-3681}, abstract = {Putnam's criticisms of the identity theory attack a straw man. Fodor's criticisms of reduction attack a straw man. Properly interpreted, Nagel offered a conception of reduction that captures everything a physicalist could want. I update Nagel, introducing the idea of overlap, and show why multiple realization poses no challenge to reduction so construed.}, } @article {pmid29609769, year = {2018}, author = {Manafu, A}, title = {Introduction: Multiple Realizability and Levels of Reality.}, journal = {Studies in history and philosophy of science}, volume = {68}, number = {}, pages = {1-2}, doi = {10.1016/j.shpsa.2018.01.013}, pmid = {29609769}, issn = {0039-3681}, } @article {pmid29609662, year = {2018}, author = {Salbach, NM and Howe, JA and Baldry, D and Merali, S and Munce, SEP}, title = {Considerations for expanding community exercise programs incorporating a healthcare-recreation partnership for people with balance and mobility limitations: a mixed methods evaluation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {214}, pmid = {29609662}, issn = {1756-0500}, mesh = {Canada ; Caregivers/statistics & numerical data ; Delivery of Health Care/*methods/organization & administration ; Exercise/*physiology ; Exercise Therapy/*methods/organization & administration ; Fitness Centers/organization & administration ; Health Personnel/statistics & numerical data ; Health Services Accessibility/organization & administration ; Humans ; *Mobility Limitation ; Program Evaluation ; *Recreation ; Social Welfare ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: To increase access to safe and appropriate exercise for people with balance and mobility limitations, community organizations have partnered with healthcare providers to deliver an evidence-based, task-oriented group exercise program in community centers in Canada. We aimed to understand challenges and solutions to implementing this program model to inform plans for expansion.

RESULTS: At a 1-day meeting, 53 stakeholders (healthcare/recreation personnel, program participants/caregivers, researchers) identified challenges to program implementation that were captured by seven themes: Resources to deliver the exercise class (e.g., difficulty finding instructors with the skills to work with people with mobility limitations); Program marketing (e.g., to foster healthcare referrals); Transportation (e.g., particularly from rural areas); Program access (e.g., program full); Maintaining program integrity; Sustaining partnerships (i.e., with healthcare partners); and Funding (e.g., to deliver program or register). Stakeholders prioritized solutions to form an action plan. A survey of individuals supervising 28 programs revealed that people with stroke, acquired brain injury, multiple sclerosis, and Parkinson's disease register at 95-100% of centers. The most prevalent issues with program fidelity across centers were not requiring a minimum level of walking ability (32%), class sizes exceeding 12 (21%), and instructor-to-participant ratios exceeding 1:4 (19%). Findings provide considerations for program expansion.}, } @article {pmid29609655, year = {2018}, author = {van de Water, JAJM and Allemand, D and Ferrier-Pagès, C}, title = {Host-microbe interactions in octocoral holobionts - recent advances and perspectives.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {64}, pmid = {29609655}, issn = {2049-2618}, mesh = {Animal Diseases/microbiology ; Animals ; Anthozoa/*microbiology ; Bacteria/classification ; Biological Products ; Coral Reefs ; Drug Discovery ; Ecosystem ; Fungi/classification ; *Host Microbial Interactions ; Host-Pathogen Interactions/immunology ; *Microbiota ; Spatio-Temporal Analysis ; Symbiosis ; Viruses/classification/genetics ; }, abstract = {Octocorals are one of the most ubiquitous benthic organisms in marine ecosystems from the shallow tropics to the Antarctic deep sea, providing habitat for numerous organisms as well as ecosystem services for humans. In contrast to the holobionts of reef-building scleractinian corals, the holobionts of octocorals have received relatively little attention, despite the devastating effects of disease outbreaks on many populations. Recent advances have shown that octocorals possess remarkably stable bacterial communities on geographical and temporal scales as well as under environmental stress. This may be the result of their high capacity to regulate their microbiome through the production of antimicrobial and quorum-sensing interfering compounds. Despite decades of research relating to octocoral-microbe interactions, a synthesis of this expanding field has not been conducted to date. We therefore provide an urgently needed review on our current knowledge about octocoral holobionts. Specifically, we briefly introduce the ecological role of octocorals and the concept of holobiont before providing detailed overviews of (I) the symbiosis between octocorals and the algal symbiont Symbiodinium; (II) the main fungal, viral, and bacterial taxa associated with octocorals; (III) the dominance of the microbial assemblages by a few microbial species, the stability of these associations, and their evolutionary history with the host organism; (IV) octocoral diseases; (V) how octocorals use their immune system to fight pathogens; (VI) microbiome regulation by the octocoral and its associated microbes; and (VII) the discovery of natural products with microbiome regulatory activities. Finally, we present our perspectives on how the field of octocoral research should move forward, and the recognition that these organisms may be suitable model organisms to study coral-microbe symbioses.}, } @article {pmid29609653, year = {2018}, author = {De Vrieze, J and Pinto, AJ and Sloan, WT and Ijaz, UZ}, title = {The active microbial community more accurately reflects the anaerobic digestion process: 16S rRNA (gene) sequencing as a predictive tool.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {63}, pmid = {29609653}, issn = {2049-2618}, support = {NE/L011956/1//Natural Environment Research Council/International ; EP/M016811/1//Engineering and Physical Sciences Research Council/International ; }, mesh = {*Anaerobiosis ; Archaea/classification/genetics ; Bacteria/classification/genetics ; Biodiversity ; Metagenomics/methods ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Amplicon sequencing methods targeting the 16S rRNA gene have been used extensively to investigate microbial community composition and dynamics in anaerobic digestion. These methods successfully characterize amplicons but do not distinguish micro-organisms that are actually responsible for the process. In this research, the archaeal and bacterial community of 48 full-scale anaerobic digestion plants were evaluated on DNA (total community) and RNA (active community) level via 16S rRNA (gene) amplicon sequencing.

RESULTS: A significantly higher diversity on DNA compared with the RNA level was observed for archaea, but not for bacteria. Beta diversity analysis showed a significant difference in community composition between the DNA and RNA of both bacteria and archaea. This related with 25.5 and 42.3% of total OTUs for bacteria and archaea, respectively, that showed a significant difference in their DNA and RNA profiles. Similar operational parameters affected the bacterial and archaeal community, yet the differentiating effect between DNA and RNA was much stronger for archaea. Co-occurrence networks and functional prediction profiling confirmed the clear differentiation between DNA and RNA profiles.

CONCLUSIONS: In conclusion, a clear difference in active (RNA) and total (DNA) community profiles was observed, implying the need for a combined approach to estimate community stability in anaerobic digestion.}, } @article {pmid29609640, year = {2018}, author = {Frawley, JE and McIntyre, E and Wardle, J and Jackson, D}, title = {Is there an association between the use of complementary medicine and vaccine uptake: results of a pilot study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {217}, pmid = {29609640}, issn = {1756-0500}, support = {N/A//Endeavour College of Natural Health/ ; }, mesh = {Adolescent ; Adult ; Australia ; Child ; Complementary Therapies/*methods/statistics & numerical data ; Female ; Humans ; Male ; Middle Aged ; *Parents ; Pilot Projects ; *Surveys and Questionnaires ; Vaccination/*methods/statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: Despite the incredible success of paediatric immunisation, support is not universal. It has been suggested that complementary medicine practitioners enable vaccine rejection and his study aims to explore the relationship between complementary medicine use and paediatric vaccination. A total of 149 Australian parents were recruited via a parenting website and Facebook groups to complete an online questionnaire.

RESULTS: The majority of parents (66.4%) stated that their children's vaccination status was up-to-date. Vaccination status was associated with parental education, area of residence, income, private health insurance, and having a Health Care Card (p < 0.05). Children's vaccinations were more likely to be up-to-date if they had consulted a general practitioner in the previous 12 months (OR 21.75; p < 0.001), and less likely to be up-to-date if they had consulted a complementary medicine practitioner (OR 0.10; p < 0.001) in the same period. Concerns about vaccine safety and efficacy were the most common reasons for a child's immunisation status not being up-to-date. These findings highlight an interface between lower vaccine uptake and visits to complementary medicine practitioners. These results emphasise the need to examine the routine paediatric care practices of complementary medicine practitioners as a crucial piece of the puzzle in understanding vaccine rejection.}, } @article {pmid29609634, year = {2018}, author = {Al-Farha, AA and Khazandi, M and Hemmatzadeh, F and Jozani, R and Tearle, R and Hoare, A and Petrovski, K}, title = {Evaluation of three cryoprotectants used with bovine milk affected with Mycoplasma bovis in different freezing conditions.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {216}, pmid = {29609634}, issn = {1756-0500}, mesh = {Animals ; Cattle ; Cryopreservation/methods ; Cryoprotective Agents/*pharmacology ; Dimethyl Sulfoxide/pharmacology ; *Freezing ; Glycerol/pharmacology ; Humans ; Microbial Viability/drug effects ; *Milk ; Mycoplasma bovis/*drug effects/physiology ; Time Factors ; }, abstract = {OBJECTIVES: Currently, there is no consensus protocols regarding the combination of glycerol (GLY), gelatin or foetal bovine serum (FBS) with dimethyl sulphoxide (DMSO) as cryoprotectants for Mycoplasma bovis in bovine milk samples. This study aimed to compare different cryopreservation compounds and storage temperatures for M. bovis.

RESULTS: There were significant differences in the survival of M. bovis on different media. Differences were also observed between different storage conditions. All additives improved the survival of M. bovis in comparison to control (CON). The combination of GLY and DMSO was shown to be significantly different to CON with 57.1% (95% CI = 21.43-133.34) and 19.1% (95% CI = 11.73-60.27), respectively at week 16, and its use should be encouraged as a cryoprotectant for M. bovis at - 20 and - 80 °C. GEL/DMSO showed the highest survival rate for M. bovis with 57.14% (95% CI = 21.43-133.34) at 4 °C in comparison with CON 14.29% (95% CI = 9.60-50.39). FBS/DMSO showed the highest survival rate for the short-term preservation similarly to other additives. The evaluated cryopreservative compounds would improve survivability of M. bovis in milk for both transport and long-term storage. Hence, it is recommended to use the mentioned methods for routine transportation or storage purposes for suspicious M. bovis milk samples.}, } @article {pmid29609633, year = {2018}, author = {Bernevic, B and El-Khatib, AH and Jakubowski, N and Weller, MG}, title = {Online immunocapture ICP-MS for the determination of the metalloprotein ceruloplasmin in human serum.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {213}, pmid = {29609633}, issn = {1756-0500}, support = {HLT05//European Metrology Research Programme (EMRP)/ ; }, mesh = {Ceruloplasmin/*analysis/chemistry/isolation & purification ; Copper/*chemistry ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mass Spectrometry/*methods ; Metalloproteins/*blood/chemistry/isolation & purification ; Reproducibility of Results ; }, abstract = {OBJECTIVE: The human copper-protein ceruloplasmin (Cp) is the major copper-containing protein in the human body. The accurate determination of Cp is mandatory for the reliable diagnosis of several diseases. However, the analysis of Cp has proven to be difficult. The aim of our work was a proof of concept for the determination of a metalloprotein-based on online immunocapture ICP-MS. The immuno-affinity step is responsible for the enrichment and isolation of the analyte from serum, whereas the compound-independent quantitation with ICP-MS delivers the sensitivity, precision, and large dynamic range. Off-line ELISA (enzyme-linked immunosorbent assay) was used in parallel to confirm the elution profile of the analyte with a structure-selective method. The total protein elution was observed with the 32S mass trace. The ICP-MS signals were normalized on a 59Co signal.

RESULTS: The human copper-protein Cp could be selectively determined. This was shown with pure Cp and with a sample of human serum. The good correlation with off-line ELISA shows that Cp could be captured and eluted selectively from the anti-Cp affinity column and subsequently determined by the copper signal of ICP-MS.}, } @article {pmid29609626, year = {2018}, author = {Ayesh, BM and Al-Masri, R and Abed, AA}, title = {CHRNA5 and CHRNA3 polymorphism and lung cancer susceptibility in Palestinian population.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {218}, pmid = {29609626}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Alleles ; Arabs/genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Lung Neoplasms/*genetics ; Male ; Middle Aged ; Nerve Tissue Proteins/*genetics ; *Polymorphism, Single Nucleotide ; Receptors, Nicotinic/*genetics ; Smoking ; }, abstract = {OBJECTIVE: The genetic polymorphism (rs16969968 in CHRNA5, and rs1051730 in CHRNA3 genes) were recently shown to be associated with risk of LC. The aim of this study is to elucidate whether they predispose Palestinian individuals to lung cancer, and how is this related to smoking.

RESULTS: Frequency of the rs16969968-A allele was significantly higher in the case group (36.7%) than in normal controls (17.5%; P = 0.022; OR = 6.83 for AA and 2.81 for AG genotypes). The frequency of rs1051730-T allele was also significantly higher in the case group (46.7%) than in the control group (22.5%; P = 0.001; OR = 2.20 for TC and 13.22 for TT genotypes). Frequency of rs16969968-A allele was higher in smokers (29.1%) than nonsmokers (15.7%) regardless of lung cancer; similarly, frequency of rs1051730-T allele was also higher in smokers than in smokers (46.7% vs 22.5%, respectively). The higher the proportion of the risk allele (rs16969968-A and rs1051730-T), the higher the mean number of daily consumed cigarettes (P = 0.006). Carrying rs16969968-A and/or rs1051730-T alleles results in an increased risk to lung cancer probably by increasing the individual's tendency for heavy smoking. The allelic frequency of the rs16969968-A and rs1051730-T alleles among normal Palestinian controls is similar to different populations worldwide.}, } @article {pmid29609623, year = {2018}, author = {Tossea, SK and Adji, EG and Coulibaly, B and Ako, BA and Coulibaly, DN and Joly, P and Assi, SB and Toure, A and Jambou, R}, title = {Cross sectional study on prevalence of sickle cell alleles S and C among patients with mild malaria in Ivory Coast.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {215}, pmid = {29609623}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Alleles ; Anemia, Sickle Cell/*epidemiology/genetics ; Child ; Child, Preschool ; Comorbidity ; Cote d'Ivoire/epidemiology ; Cross-Sectional Studies ; Female ; Genotype ; Geography ; Hemoglobin C/genetics ; Hemoglobin, Sickle/genetics ; Humans ; Infant ; Infant, Newborn ; Malaria/*epidemiology ; Male ; Pregnancy ; Pregnancy Complications, Parasitic/*epidemiology ; Prevalence ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVES: Sickle cell anemia is due to a mutations on the betaglobin gene, inducing abnormal hemoglobin. In West Africa the main mutations lead to S or C types of hemoglobin. Patients with homozygote mutations seem protected against severe malaria, but not against mild disease. The prevalence of abnormal hemoglobin among patients attending dispensaries for mild malaria is thus unknown. A retrospective study was conducted to update data on the prevalence of S and C hemoglobin among patients attending dispensaries with mild malaria. Enrolment of patients was conducted during in vivo malaria treatment efficacy survey following the 42 days WHO protocol. A group of non-infected pregnant women and a group of patients with fever different from malaria, were also recruited in the same dispensaries.

RESULTS: 794 blood samples were included. S and C genotypes were found in all the regions of Ivory Coast with the highest prevalence in the Northern region (S and C genotypes, 27%). In non-infected patients, prevalence of mutations was higher than in malaria patients.

CONCLUSION: A high proportion of patients with mild malaria carried genetic hemoglobin disorder. This population of high risk must be better investigated to control treatment efficacy and to manage complications.}, } @article {pmid29609607, year = {2018}, author = {Malzer, E and Dominicus, CS and Chambers, JE and Dickens, JA and Mookerjee, S and Marciniak, SJ}, title = {The integrated stress response regulates BMP signalling through effects on translation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {34}, pmid = {29609607}, issn = {1741-7007}, support = {G1002610//Medical Research Council/United Kingdom ; ISSF//Wellcome Trust/United Kingdom ; 100140//Wellcome Trust/United Kingdom ; 093026//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Developmental pathways must be responsive to the environment. Phosphorylation of eIF2α enables a family of stress-sensing kinases to trigger the integrated stress response (ISR), which has pro-survival and developmental consequences. Bone morphogenetic proteins (BMPs) regulate multiple developmental processes in organisms from insects to mammals.

RESULTS: Here we show in Drosophila that GCN2 antagonises BMP signalling through direct effects on translation and indirectly via the transcription factor crc (dATF4). Expression of a constitutively active GCN2 or loss of the eIF2α phosphatase dPPP1R15 impairs developmental BMP signalling in flies. In cells, inhibition of translation by GCN2 blocks downstream BMP signalling. Moreover, loss of d4E-BP, a target of crc, augments BMP signalling in vitro and rescues tissue development in vivo.

CONCLUSION: These results identify a novel mechanism by which the ISR modulates BMP signalling during development.}, } @article {pmid29609562, year = {2018}, author = {Tiezzi, F and Arceo, ME and Cole, JB and Maltecca, C}, title = {Including gene networks to predict calving difficulty in Holstein, Brown Swiss and Jersey cattle.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {20}, pmid = {29609562}, issn = {1471-2156}, abstract = {BACKGROUND: Calving difficulty or dystocia has a great economic impact in the US dairy industry. Reported risk factors associated with calving difficulty are feto-pelvic disproportion, gestation length and conformation. Different dairy cattle breeds have different incidence of calving difficulty, with Holstein having the highest dystocia rates and Jersey the lowest. Genomic selection becomes important especially for complex traits with low heritability, where the accuracy of conventional selection is lower. However, for complex traits where a large number of genes influence the phenotype, genome-wide association studies showed limitations. Biological networks could overcome some of these limitations and better capture the genetic architecture of complex traits. In this paper, we characterize Holstein, Brown Swiss and Jersey breed-specific dystocia networks and employ them in genomic predictions.

RESULTS: Marker association analysis identified single nucleotide polymorphisms explaining the largest average proportion of genetic variance on BTA18 in Holstein, BTA25 in Brown Swiss, and BTA15 in Jersey. Gene networks derived from the genome-wide association included 1272 genes in Holstein, 1454 genes in Brown Swiss, and 1455 genes in Jersey. Furthermore, 256 genes in Holstein network, 275 genes in the Brown Swiss network, and 253 genes in the Jersey network were within previously reported dystocia quantitative trait loci. The across-breed network included 80 genes, with 9 genes being within previously reported dystocia quantitative trait loci. The gene-gene interactions in this network differed in the different breeds. Gene ontology enrichment analysis of genes in the networks showed Regulation of ARF GTPase was very significant (FDR ≤ 0.0098) on Holstein. Neuron morphogenesis and differentiation was the term most enriched (FDR ≤ 0.0539) on the across-breed network. Genomic prediction models enriched with network-derived relationship matrices did not outperform regular GBLUP models.

CONCLUSIONS: Regions identified in the genome were in the proximity of previously described quantitative trait loci that would most likely affect calving difficulty by altering the feto-pelvic proportion. Inclusion of identified networks did not increase prediction accuracy. The approach used in this paper could be extended to any instance with asymmetric distribution of phenotypes, for example, resistance to disease data.}, } @article {pmid29609551, year = {2018}, author = {Feng, X and Yu, X and Fu, B and Wang, X and Liu, H and Pang, M and Tong, J}, title = {A high-resolution genetic linkage map and QTL fine mapping for growth-related traits and sex in the Yangtze River common carp (Cyprinus carpio haematopterus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {230}, pmid = {29609551}, issn = {1471-2164}, support = {XDA0810405//Chinese Academy of Sciences/ ; 2016FBZ05//FEBL Program/ ; 2010CB126305//MOST 973 Project/ ; }, mesh = {Animals ; Aquaculture ; Carps/genetics/*growth & development ; Chromosome Mapping/*methods ; Female ; Fish Proteins/genetics ; Genetic Linkage ; Male ; Phenotype ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: A high-density genetic linkage map is essential for QTL fine mapping, comparative genome analysis, identification of candidate genes and marker-assisted selection for economic traits in aquaculture species. The Yangtze River common carp (Cyprinus carpio haematopterus) is one of the most important aquacultured strains in China. However, quite limited genetics and genomics resources have been developed for genetic improvement of economic traits in such strain.

RESULTS: A high-resolution genetic linkage map was constructed by using 7820 2b-RAD (2b-restriction site-associated DNA) and 295 microsatellite markers in a F2 family of the Yangtze River common carp (C. c. haematopterus). The length of the map was 4586.56 cM with an average marker interval of 0.57 cM. Comparative genome mapping revealed that a high proportion (70%) of markers with disagreed chromosome location was observed between C. c. haematopterus and another common carp strain (subspecies) C. c. carpio. A clear 2:1 relationship was observed between C. c. haematopterus linkage groups (LGs) and zebrafish (Danio rerio) chromosomes. Based on the genetic map, 21 QTLs for growth-related traits were detected on 12 LGs, and contributed values of phenotypic variance explained (PVE) ranging from 16.3 to 38.6%, with LOD scores ranging from 4.02 to 11.13. A genome-wide significant QTL (LOD = 10.83) and three chromosome-wide significant QTLs (mean LOD = 4.84) for sex were mapped on LG50 and LG24, respectively. A 1.4 cM confidence interval of QTL for all growth-related traits showed conserved synteny with a 2.06 M segment on chromosome 14 of D. rerio. Five potential candidate genes were identified by blast search in this genomic region, including a well-studied multi-functional growth related gene, Apelin.

CONCLUSIONS: We mapped a set of suggestive and significant QTLs for growth-related traits and sex based on a high-density genetic linkage map using SNP and microsatellite markers for Yangtze River common carp. Several candidate growth genes were also identified from the QTL regions by comparative mapping. This genetic map would provide a basis for genome assembly and comparative genomics studies, and those QTL-derived candidate genes and genetic markers are useful genomic resources for marker-assisted selection (MAS) of growth-related traits in the Yangtze River common carp.}, } @article {pmid29609549, year = {2018}, author = {Howe, DG}, title = {A statistical approach to identify, monitor, and manage incomplete curated data sets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {110}, pmid = {29609549}, issn = {1471-2105}, support = {HG002659/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; *Data Mining ; *Databases, Genetic ; Gene Expression Regulation ; Molecular Sequence Annotation ; Regression Analysis ; Reproducibility of Results ; *Statistics as Topic ; Zebrafish/*genetics ; }, abstract = {BACKGROUND: Many biological knowledge bases gather data through expert curation of published literature. High data volume, selective partial curation, delays in access, and publication of data prior to the ability to curate it can result in incomplete curation of published data. Knowing which data sets are incomplete and how incomplete they are remains a challenge. Awareness that a data set may be incomplete is important for proper interpretation, to avoiding flawed hypothesis generation, and can justify further exploration of published literature for additional relevant data. Computational methods to assess data set completeness are needed. One such method is presented here.

RESULTS: In this work, a multivariate linear regression model was used to identify genes in the Zebrafish Information Network (ZFIN) Database having incomplete curated gene expression data sets. Starting with 36,655 gene records from ZFIN, data aggregation, cleansing, and filtering reduced the set to 9870 gene records suitable for training and testing the model to predict the number of expression experiments per gene. Feature engineering and selection identified the following predictive variables: the number of journal publications; the number of journal publications already attributed for gene expression annotation; the percent of journal publications already attributed for expression data; the gene symbol; and the number of transgenic constructs associated with each gene. Twenty-five percent of the gene records (2483 genes) were used to train the model. The remaining 7387 genes were used to test the model. One hundred and twenty-two and 165 of the 7387 tested genes were identified as missing expression annotations based on their residuals being outside the model lower or upper 95% confidence interval respectively. The model had precision of 0.97 and recall of 0.71 at the negative 95% confidence interval and precision of 0.76 and recall of 0.73 at the positive 95% confidence interval.

CONCLUSIONS: This method can be used to identify data sets that are incompletely curated, as demonstrated using the gene expression data set from ZFIN. This information can help both database resources and data consumers gauge when it may be useful to look further for published data to augment the existing expertly curated information.}, } @article {pmid29609544, year = {2018}, author = {Ben Yahia, H and Ben Sallem, R and Tayh, G and Klibi, N and Ben Amor, I and Gharsa, H and Boudabbous, A and Ben Slama, K}, title = {Detection of CTX-M-15 harboring Escherichia coli isolated from wild birds in Tunisia.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {26}, pmid = {29609544}, issn = {1471-2180}, abstract = {BACKGROUND: The spreading of antibiotic resistant bacteria is becoming nowadays an alarming threat to human and animal health. There is increasing evidence showing that wild birds could significantly contribute to the transmission and spreading of drug-resistant bacteria. However, data for antimicrobial resistance in wild birds remain scarce, especially throughout Africa. The aims of this investigation were to analyze the prevalence of ESBL-producing E. coli in faecal samples of wild birds in Tunisia and to characterize the recovered isolates.

RESULTS: One hundred and eleven samples were inoculated on MacConkey agar plates supplemented with cefotaxime (2 μg/ml). ESBL-producing E. coli isolates were detected in 12 of 111 faecal samples (10.81%) and one isolate per sample was further characterized. β-lactamase detected genes were as follows: blaCTX-M-15 (8 isolates), blaCTX-M-15 + blaTEM-1b (4 isolates). The ISEcp1 and orf477 sequences were found respectively in the regions upstream and downstream of all blaCTX-M-15 genes. Seven different plasmid profiles were observed among the isolates. IncF (FII, FIA, FIB) and IncW replicons were identified in 11 CTX-M-15 producing isolates, and mostly, other replicons were also identified: IncHI2, IncA/C, IncP, IncI1 and IncX. All ESBL-producing E. coli isolates were integron positive and possessed "empty" integron structures with no inserted region of DNA. The following detected virulence genes were: (number of isolates in parentheses): fimA (ten); papC (seven); aer (five); eae (one); and papGIII, hly, cnf, and bfp (none). Molecular typing using pulsed-field gel electrophoresis and multilocus sequence typing showed a low genetic heterogeneity among the 12 ESBL-producing strains with five unrelated PFGE types and five different sequence types (STs) respectively. CTX-M-15-producing isolates were ascribed to phylogroup A (eleven isolates) and B2 (one isolate).

CONCLUSION: To our knowledge, this study provides the first insight into the contribution of wild birds to the dynamics of ESBL-producing E. coli in Tunisia.}, } @article {pmid29609543, year = {2018}, author = {Gao, X and Ye, J and Yang, C and Luo, L and Liu, Y and Ding, J and Zhang, Y and Ling, Y and Huang, W and Zhang, X and Zhang, K and Li, X and Zhou, J and Fang, F and Cao, Z}, title = {RNA-seq analysis of lncRNA-controlled developmental gene expression during puberty in goat & rat.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {19}, pmid = {29609543}, issn = {1471-2156}, support = {31472096//National Natural Science Foundation of China/ ; 31301934//National Natural Science Foundation of China/ ; 2014ZX08008-005-004//National Transgenenic New Species Breeding Program of China/ ; 1508085MC54//Natural Science Foundation of Anhui Province/ ; }, abstract = {BACKGROUND: Puberty is a pivotal stage in female animal development, and marks the onset of reproductive capability. However, little is known about the function of lncRNAs (long noncoding RNAs) in puberty. Therefore, RNA-seq analysis were performed between goats and rats to clarify the roles of lncRNAs and mRNAs in the onset of puberty.

RESULTS: In the present study, the length of lncRNAs, the length of the open reading frame and the exon count were compared between the two species. Furthermore, functional annotation analysis based on Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analysis of lncRNAs target genes and differentially expressed mRNA demonstrated the significantly enriched terms, such as AMPK signaling pathway, oxytocin signaling pathway, insulin secretion as well as pheromone receptor activity, and some other signaling pathways which were involved in the regulation of female puberty. Moreover, our results of siRNA interference in vitro showed the candidate lncRNA XLOC_446331 may play a crucial role in regulating female puberty.

CONCLUSION: In conclusion, the RNA-seq analysis between goat and rat provide novel candidate regulators for genetic and molecular studies on female puberty.}, } @article {pmid29609542, year = {2018}, author = {Bagi, A and Riiser, ES and Molland, HS and Star, B and Haverkamp, THA and Sydnes, MO and Pampanin, DM}, title = {Gastrointestinal microbial community changes in Atlantic cod (Gadus morhua) exposed to crude oil.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {25}, pmid = {29609542}, issn = {1471-2180}, abstract = {BACKGROUND: The expansion of offshore oil exploration increases the risk of marine species being exposed to oil pollution in currently pristine areas. The adverse effects of oil exposure through toxic properties of polycyclic aromatic hydrocarbons (PAHs) have been well studied in Atlantic cod (Gadus morhua). Nevertheless, the fate of conjugated metabolites in the intestinal tract and their effect on the diversity of intestinal microbial community in fish is less understood. Here, we investigated the intestinal microbial community composition of Atlantic cod after 28 days of exposure to crude oil (concentration range 0.0-0.1 mg/L).

RESULTS: Analysis of PAH metabolites in bile samples confirmed that uptake and biotransformation of oil compounds occurred as a result of the exposure. Various evidence for altered microbial communities was found in fish exposed to high (0.1 mg/L) and medium (0.05 mg/L) concentrations of oil when compared to fish exposed to low oil concentration (0.01 mg/L) or no oil (control). First, altered banding patterns were observed on denaturing gradient gel electrophoresis for samples pooled from each treatment group. Secondly, based on 16S rRNA sequences, higher levels of oil exposure were associated with a loss of overall diversity of the gut microbial communities. Furthermore, 8 operational taxonomic units (OTUs) were found to have significantly different relative abundances in samples from fishes exposed to high and medium oil concentrations when compared to samples from the control group and low oil concentration. Among these, only one OTU, a Deferribacterales, had increased relative abundance in samples from fish exposed to high oil concentration.

CONCLUSIONS: The results presented herein contribute to a better understanding of the effects of oil contamination on the gut microbial community changes in fish and highlight the importance of further studies into the area. Our findings suggest that increased relative abundance of bacteria belonging to the order Deferribacterales may be indicative of exposure to oil at concentrations higher than 0.05 mg/L.}, } @article {pmid29609541, year = {2018}, author = {Zhang, Z and Popov, LE and Holmer, LE and Zhang, Z}, title = {Earliest ontogeny of early Cambrian acrotretoid brachiopods - first evidence for metamorphosis and its implications.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {42}, pmid = {29609541}, issn = {1471-2148}, support = {41425008//National Natural Science Foundation of China (CN)/International ; 41720104002//National Natural Science Foundation of China (CN)/International ; 41621003//National Natural Science Foundation of China/International ; 41772002//National Natural Science Foundation of China/International ; 2013CB835002//National 973 program/International ; D17013//111 projects of China/International ; VR 2012-1658//Swedish Research Council/International ; }, mesh = {Animal Shells/anatomy & histology ; Animals ; Fossils ; Invertebrates/anatomy & histology/*growth & development ; *Metamorphosis, Biological ; Phylogeny ; }, abstract = {BACKGROUND: Our understanding of the ontogeny of Palaeozoic brachiopods has changed significantly during the last two decades. However, the micromorphic acrotretoids have received relatively little attention, resulting in a poor knowledge of their ontogeny, origin and earliest evolution. The uniquely well preserved early Cambrian fossil records in South China provide a great new opportunity to investigate the phylogenetically important ontogeny of the earliest acrotretoid brachiopods, and give new details of the dramatic changes in anatomy of acrotretoid brachiopods during the transition from planktotrophic larvae to filter feeding sedentary juveniles.

RESULTS: Well preserved specimens of the earliest Cambrian acrotretoid brachiopods Eohadrotreta zhenbaensis and Eohadrotreta? zhujiahensis (Cambrian Series 2, Shuijingtuo Formation, Three Gorges area, South China) provide new insights into early acrotretoid ontogeny, and have significance for elucidating the poorly understood early phylogeny of the linguliform brachiopods. A more comprehensive understanding of the applied terminology based on new observation, especially in definition of the major growth stages (embryo, planktotrophic larva, post-metamorphically sessile juvenile and adult), is established. The so-called acrotretoid "larval shell" of both valves of Eohadrotreta demonstrates evidence for metamorphosis (shedding of the larval setae and transitions of shell secretion), during the planktotrophic stage. Therefore, it is here termed the metamorphic shell. The inferred early acrotretoid larval body plan included a bivalved protegulum, secreted at the beginning of the pelagic stage, which later developed two pairs of larval dorsal setal sacs and anterior-posterior alignment of the gut during metamorphosis.

CONCLUSION: The primary larval body plan of acrotretoid Eohadrotreta is now known to have been shared with most early linguliforms and their relatives (including paterinates, siphonotretoids, early linguloids, the problematic mickwitziids, as well as many early rhynchonelliforms). It is suggested that this type of earliest ontogeny can be considered as plesiomorphic for the Brachiopoda and probably first evolved in stem group brachiopods with subsequent heterochronic changes.}, } @article {pmid29608962, year = {2018}, author = {Bover, P and Mitchell, KJ and Llamas, B and Rofes, J and Thomson, VA and Cuenca-Bescós, G and Alcover, JA and Cooper, A and Pons, J}, title = {Molecular phylogenetics supports the origin of an endemic Balearic shrew lineage (Nesiotites) coincident with the Messinian Salinity Crisis.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {188-195}, doi = {10.1016/j.ympev.2018.03.028}, pmid = {29608962}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Calibration ; Caves ; DNA, Mitochondrial/genetics ; Evolution, Molecular ; Fossils ; Genome, Mitochondrial ; *Phylogeny ; *Salinity ; Shrews/*classification/genetics ; }, abstract = {The red-toothed shrews (Soricinae) are the most widespread subfamily of shrews, distributed from northern South America to North America and Eurasia. Within this subfamily, the tribe Nectogalini includes the fossil species Nesiotites hidalgo recorded from the Late Pleistocene to Holocene of the Balearic Islands (Western Mediterranean). Although there is a consensus about the close relationship between the extinct red-toothed shrew genera Nesiotites and Asoriculus based on morphology, molecular data are necessary to further evaluate the phylogenetic relationships of the Balearic fossils. We obtained a near complete mitochondrial genome of N. hidalgo, allowing the first molecular phylogenetic analysis of this species. Analyses based on 15,167 bp of the mitochondrial genome placed N. hidalgo as close relative to the extant Himalayan shrew (Soriculus nigrescens), and a combined analysis using molecular and morphological data confirm that N. hidalgo and Asoriculus gibberodon are sister-taxa with S. nigrescens as the immediate outgroup. Molecular clock and divergence estimates suggest that the split between N. hidalgo and its closest living relative occurred around 6.44 Ma, which is in agreement with the previously proposed colonisation of the Balearic Islands from mainland Europe by nectogaline shrews during the Messinian Salinity Crisis (5.97-5.33 My ago). Our results highlight that it is possible to retrieve genetic data from extinct small mammals from marginal environments for DNA preservation. Additional finds from the fossil record of Soricinae from the Eurasian Late Miocene/Early Pliocene are needed to shed further light on the still confusing taxonomy and paleobiogeography of this clade.}, } @article {pmid29608877, year = {2018}, author = {Dark, C and Homman-Ludiye, J and Bryson-Richardson, RJ}, title = {The role of ADHD associated genes in neurodevelopment.}, journal = {Developmental biology}, volume = {438}, number = {2}, pages = {69-83}, doi = {10.1016/j.ydbio.2018.03.023}, pmid = {29608877}, issn = {1095-564X}, mesh = {Attention Deficit Disorder with Hyperactivity/etiology/*genetics ; Brain/physiopathology ; Humans ; Impulsive Behavior ; Neurodevelopmental Disorders/genetics ; Neurons/physiology ; Synapses/genetics/physiology ; }, abstract = {Attention deficit hyperactivity disorder (ADHD) is a highly heritable neurodevelopmental disorder of childhood. It is primarily characterised by high levels of activity, inattention, and impulsivity, and has strong negative impacts on academic functioning. Children with ADHD show a reduction in volume, and hypoactivity, in a range of brain regions. The underlying mechanisms behind these phenotypes are unknown, however, variants in several genes with known roles in neurodevelopment are associated with ADHD. In this review we discuss how these ADHD associated genes contribute to neurodevelopment, and how variants in these genes could give rise to the neurological phenotypes seen in ADHD.}, } @article {pmid29608732, year = {2018}, author = {Hönigschmid, P and Bykova, N and Schneider, R and Ivankov, D and Frishman, D}, title = {Evolutionary Interplay between Symbiotic Relationships and Patterns of Signal Peptide Gain and Loss.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {928-938}, pmid = {29608732}, issn = {1759-6653}, mesh = {Enterobacteriaceae/genetics ; *Evolution, Molecular ; Genome, Bacterial/genetics ; *Phylogeny ; Protein Sorting Signals/*genetics ; Symbiosis/*genetics ; }, abstract = {Can orthologous proteins differ in terms of their ability to be secreted? To answer this question, we investigated the distribution of signal peptides within the orthologous groups of Enterobacterales. Parsimony analysis and sequence comparisons revealed a large number of signal peptide gain and loss events, in which signal peptides emerge or disappear in the course of evolution. Signal peptide losses prevail over gains, an effect which is especially pronounced in the transition from the free-living or commensal to the endosymbiotic lifestyle. The disproportionate decline in the number of signal peptide-containing proteins in endosymbionts cannot be explained by the overall reduction of their genomes. Signal peptides can be gained and lost either by acquisition/elimination of the corresponding N-terminal regions or by gradual accumulation of mutations. The evolutionary dynamics of signal peptides in bacterial proteins represents a powerful mechanism of functional diversification.}, } @article {pmid29608731, year = {2018}, author = {Petersen, G and Zervas, A and Pedersen, HÆ and Seberg, O}, title = {Genome Reports: Contracted Genes and Dwarfed Plastome in Mycoheterotrophic Sciaphila thaidanica (Triuridaceae, Pandanales).}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {976-981}, pmid = {29608731}, issn = {1759-6653}, mesh = {Autotrophic Processes/genetics ; *Evolution, Molecular ; Genome, Plastid/*genetics ; Heterotrophic Processes/genetics ; Magnoliopsida/genetics ; Photosynthesis/*genetics ; *Phylogeny ; Seeds/genetics ; }, abstract = {With a reduced need for photosynthesis, the plastome of parasitic and mycoheterotrophic plants degrades. In the tiny, fully mycoheterotrophic plant Sciaphila thaidanica, we find one of the smallest plastomes yet encountered. Its size is just 12,780 bp and it contains only 20 potentially functional housekeeping genes. Thus S. thaidanica fits the proposed model of gene loss in achlorophyllous plants. The most astonishing feature of the plastome is its extremely compact nature, with more than half of the genes having overlapping reading frames. Additionally, intergenic sequences have been reduced to a bare minimum, and the retained genes have been reduced in length both compared with the orthologous genes in another mycoheterotrophic species of Sciaphila and in the autotrophic relative Carludovica.}, } @article {pmid29608730, year = {2018}, author = {Bitarello, BD and de Filippo, C and Teixeira, JC and Schmidt, JM and Kleinert, P and Meyer, D and Andrés, AM}, title = {Signatures of Long-Term Balancing Selection in Human Genomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {939-955}, pmid = {29608730}, issn = {1759-6653}, mesh = {Alleles ; Animals ; *Evolution, Molecular ; Genetic Variation ; Genetics, Population ; Genome, Human/*genetics ; Humans ; Pan troglodytes/genetics ; Polymorphism, Single Nucleotide ; *Selection, Genetic ; }, abstract = {Balancing selection maintains advantageous diversity in populations through various mechanisms. Although extensively explored from a theoretical perspective, an empirical understanding of its prevalence and targets lags behind our knowledge of positive selection. Here, we describe the Non-central Deviation (NCD), a simple yet powerful statistic to detect long-term balancing selection (LTBS) that quantifies how close frequencies are to expectations under LTBS, and provides the basis for a neutrality test. NCD can be applied to a single locus or genomic data, and can be implemented considering only polymorphisms (NCD1) or also considering fixed differences with respect to an outgroup (NCD2) species. Incorporating fixed differences improves power, and NCD2 has higher power to detect LTBS in humans under different frequencies of the balanced allele(s) than other available methods. Applied to genome-wide data from African and European human populations, in both cases using chimpanzee as an outgroup, NCD2 shows that, albeit not prevalent, LTBS affects a sizable portion of the genome: ∼0.6% of analyzed genomic windows and 0.8% of analyzed positions. Significant windows (P < 0.0001) contain 1.6% of SNPs in the genome, which disproportionally fall within exons and change protein sequence, but are not enriched in putatively regulatory sites. These windows overlap ∼8% of the protein-coding genes, and these have larger number of transcripts than expected by chance even after controlling for gene length. Our catalog includes known targets of LTBS but a majority of them (90%) are novel. As expected, immune-related genes are among those with the strongest signatures, although most candidates are involved in other biological functions, suggesting that LTBS potentially influences diverse human phenotypes.}, } @article {pmid29608729, year = {2018}, author = {Zhou, X and Sun, D and Guang, X and Ma, S and Fang, X and Mariotti, M and Nielsen, R and Gladyshev, VN and Yang, G}, title = {Molecular Footprints of Aquatic Adaptation Including Bone Mass Changes in Cetaceans.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {967-975}, pmid = {29608729}, issn = {1759-6653}, support = {P01 AG047200/AG/NIA NIH HHS/United States ; R01 GM065204/GM/NIGMS NIH HHS/United States ; R37 GM065204/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; Animals ; *Bone and Bones ; Cetacea/*genetics/physiology ; }, abstract = {Cetaceans (whales, dolphins, and porpoises) are a group of specialized mammals that evolved from terrestrial ancestors and are fully adapted to aquatic habitats. Taking advantage of the recently sequenced finless porpoise genome, we conducted comparative analyses of the genomes of seven cetaceans and related terrestrial species to provide insight into the molecular bases of adaptation of these aquatic mammals. Changes in gene sequences were identified in main lineages of cetaceans, offering an evolutionary picture of cetacean genomes that reveal new pathways that could be associated with adaptation to aquatic lifestyle. We profiled bone microanatomical structures across 28 mammals, including representatives of cetaceans, pinnipeds, and sirenians. Subsequent phylogenetic comparative analyses revealed genes (including leptin, insulin-like growth factor 1, and collagen type I alpha 2 chain) with the root-to-tip substitution rate significantly correlated with bone compactness, implicating these genes could be involved in bone mass control. Overall, this study described adjustments of the genomes of cetaceans according to lifestyle, phylogeny, and bone mass.}, } @article {pmid29608728, year = {2018}, author = {Zheng, W and Wang, C and Yan, Y and Gao, F and Doak, TG and Song, W}, title = {Insights into an Extensively Fragmented Eukaryotic Genome: De Novo Genome Sequencing of the Multinuclear Ciliate Uroleptopsis citrina.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {883-894}, pmid = {29608728}, issn = {1759-6653}, mesh = {Amino-Acid N-Acetyltransferase/genetics ; Chromosome Mapping ; Ciliophora/*genetics ; Genome, Protozoan/*genetics ; Genomics ; Telomere/genetics ; *Whole Genome Sequencing ; }, abstract = {Ciliated protists are a large group of single-celled eukaryotes with separate germline and somatic nuclei in each cell. The somatic genome is developed from the zygotic nucleus through a series of chromosomal rearrangements, including fragmentation, DNA elimination, de novo telomere addition, and DNA amplification. This unique feature makes them perfect models for research in genome biology and evolution. However, genomic research of ciliates has been limited to a few species, owing to problems with DNA contamination and obstacles in cultivation. Here, we introduce a method combining telomere-primer PCR amplification and high-throughput sequencing, which can reduce DNA contamination and obtain genomic data efficiently. Based on this method, we report a draft somatic genome of a multimacronuclear ciliate, Uroleptopsis citrina. 1) The telomeric sequence in U. citrina is confirmed to be C4A4C4A4C4 by directly blunt-end cloning. 2) Genomic analysis of the resulting chromosomes shows a "one-gene one-chromosome" pattern, with a small number of multiple-gene chromosomes. 3) Amino acid usage is analyzed, and reassignment of stop codons is confirmed. 4) Chromosomal analysis shows an obvious asymmetrical GC skew and high bias between A and T in the subtelomeric regions of the sense-strand, with the detection of an 11-bp high AT motif region in the 3' subtelomeric region. 5) The subtelomeric sequence also has an obvious 40 nt strand oscillation of nucleotide ratio. 6) In the 5' subtelomeric region of the coding strand, the distribution of potential TATA-box regions is illustrated, which accumulate between 30 and 50 nt. This work provides a valuable reference for genomic research and furthers our understanding of the dynamic nature of unicellular eukaryotic genomes.}, } @article {pmid29608727, year = {2018}, author = {Shriner, D and Tekola-Ayele, F and Adeyemo, A and Rotimi, CN}, title = {Genetic Ancestry of Hadza and Sandawe Peoples Reveals Ancient Population Structure in Africa.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {875-882}, pmid = {29608727}, issn = {1759-6653}, support = {ZIA HG200362/HG/NHGRI NIH HHS/United States ; }, mesh = {African Continental Ancestry Group/*genetics ; DNA, Ancient ; *Genetics, Population ; Genome, Human/*genetics ; Haplotypes/genetics ; Humans ; Tanzania ; }, abstract = {The Hadza and Sandawe populations in present-day Tanzania speak languages containing click sounds and therefore thought to be distantly related to southern African Khoisan languages. We analyzed genome-wide genotype data for individuals sampled from the Hadza and Sandawe populations in the context of a global data set of 3,528 individuals from 163 ethno-linguistic groups. We found that Hadza and Sandawe individuals share ancestry distinct from and most closely related to Omotic ancestry; share Khoisan ancestry with populations such as ≠Khomani, Karretjie, and Ju/'hoansi in southern Africa; share Niger-Congo ancestry with populations such as Yoruba from Nigeria and Luhya from Kenya, consistent with migration associated with the Bantu Expansion; and share Cushitic ancestry with Somali, multiple Ethiopian populations, the Maasai population in Kenya, and the Nama population in Namibia. We detected evidence for low levels of Arabian, Nilo-Saharan, and Pygmy ancestries in a minority of individuals. Our results indicate that west Eurasian ancestry in eastern Africa is more precisely the Arabian parent of Cushitic ancestry. Relative to the Out-of-Africa migrations, Hadza ancestry emerged early whereas Sandawe ancestry emerged late.}, } @article {pmid29608726, year = {2018}, author = {Käfer, J and Betancourt, A and Villain, AS and Fernandez, M and Vignal, C and Marais, GAB and Tenaillon, MI}, title = {Progress and Prospects in Gender Visibility at SMBE Annual Meetings.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {901-908}, pmid = {29608726}, issn = {1759-6653}, mesh = {Female ; Humans ; Molecular Biology/*trends ; *Science ; *Women, Working ; Workforce ; }, abstract = {Reduced visibility of women in science is thought to be one of the causes of their underrepresentation among scientists, in particular at senior positions. Visibility is achieved through publications, and through conference attendance and presentations. Here, we investigated gender differences in visibility at the annual meetings of the Society of Molecular Biology and Evolution. The analysis of meeting programs showed a regular increase in female speakers for the last 16 years. Data on abstract submission suggest that there are no gender-related preferences in the acceptance of contributed presentations at the most recent meetings. However, data collected on-site in 2015 and 2016 show that women asked only ∼25% of the questions, that is, much less than expected given the female attendance. Understanding the reasons for this pattern is necessary for the development of policies that aim to reduce imbalance in visibility.}, } @article {pmid29608725, year = {2018}, author = {Zehra, R and Abbasi, AA}, title = {Homo sapiens-Specific Binding Site Variants within Brain Exclusive Enhancers Are Subject to Accelerated Divergence across Human Population.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {956-966}, pmid = {29608725}, issn = {1759-6653}, mesh = {Animals ; Binding Sites/genetics ; Brain/metabolism ; Enhancer Elements, Genetic/*genetics ; *Evolution, Molecular ; Humans ; Primates/*genetics ; Species Specificity ; Transcription Factors/genetics ; }, abstract = {Empirical assessments of human accelerated noncoding DNA frgaments have delineated presence of many cis-regulatory elements. Enhancers make up an important category of such accelerated cis-regulatory elements that efficiently control the spatiotemporal expression of many developmental genes. Establishing plausible reasons for accelerated enhancer sequence divergence in Homo sapiens has been termed significant in various previously published studies. This acceleration by including closely related primates and archaic human data has the potential to open up evolutionary avenues for deducing present-day brain structure. This study relied on empirically confirmed brain exclusive enhancers to avoid any misjudgments about their regulatory status and categorized among them a subset of enhancers with an exceptionally accelerated rate of lineage specific divergence in humans. In this assorted set, 13 distinct transcription factor binding sites were located that possessed unique existence in humans. Three of 13 such sites belonging to transcription factors SOX2, RUNX1/3, and FOS/JUND possessed single nucleotide variants that made them unique to H. sapiens upon comparisons with Neandertal and Denisovan orthologous sequences. These variants modifying the binding sites in modern human lineage were further substantiated as single nucleotide polymorphisms via exploiting 1000 Genomes Project Phase3 data. Long range haplotype based tests laid out evidence of positive selection to be governing in African population on two of the modern human motif modifying alleles with strongest results for SOX2 binding site. In sum, our study acknowledges acceleration in noncoding regulatory landscape of the genome and highlights functional parts within it to have undergone accelerated divergence in present-day human population.}, } @article {pmid29608724, year = {2018}, author = {Payne, BL and Alvarez-Ponce, D}, title = {Higher Rates of Protein Evolution in the Self-Fertilizing Plant Arabidopsis thaliana than in the Out-Crossers Arabidopsis lyrata and Arabidopsis halleri.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {895-900}, pmid = {29608724}, issn = {1759-6653}, mesh = {Arabidopsis/*genetics/growth & development ; *Evolution, Molecular ; Genome, Plant/genetics ; Polymorphism, Genetic ; Population Density ; Selection, Genetic/*genetics ; Self-Fertilization/genetics ; }, abstract = {The common transition from out-crossing to self-fertilization in plants decreases effective population size. This is expected to result in a reduced efficacy of natural selection and in increased rates of protein evolution in selfing plants compared with their outcrossing congeners. Prior analyses, based on a very limited number of genes, detected no differences between the rates of protein evolution in the selfing Arabidopsis thaliana compared with the out-crosser Arabidopsis lyrata. Here, we reevaluate this trend using the complete genomes of A. thaliana, A. lyrata, Arabidopsis halleri, and the outgroups Capsella rubella and Thellungiella parvula. Our analyses indicate slightly but measurably higher nonsynonymous divergences (dN), synonymous divergences (dS) and dN/dS ratios in A. thaliana compared with the other Arabidopsis species, indicating that purifying selection is indeed less efficacious in A. thaliana.}, } @article {pmid29608723, year = {2018}, author = {Forni, D and Pontremoli, C and Pozzoli, U and Clerici, M and Cagliani, R and Sironi, M}, title = {Ancient Evolution of Mammarenaviruses: Adaptation via Changes in the L Protein and No Evidence for Host-Virus Codivergence.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {863-874}, pmid = {29608723}, issn = {1759-6653}, mesh = {Acclimatization/genetics ; Africa ; Animals ; Arenaviridae/*genetics/pathogenicity ; Host-Pathogen Interactions/*genetics ; Latin America ; Murinae/genetics/*virology ; *Phylogeography ; }, abstract = {The Mammarenavirus genus includes several pathogenic species of rodent-borne viruses. Old World (OW) mammarenaviruses infect rodents in the Murinae subfamily and are mainly transmitted in Africa and Asia; New World (NW) mammarenaviruses are found in rodents of the Cricetidae subfamily in the Americas. We applied a selection-informed method to estimate that OW and NW mammarenaviruses diverged less than ∼45,000 years ago (ya). By incorporating phylogeographic inference, we show that NW mammarenaviruses emerged in the Latin America-Caribbean region ∼41,400-3,300 ya, whereas OW mammarenaviruses originated ∼23,100-1,880 ya, most likely in Southern Africa. Cophylogenetic analysis indicated that cospeciation did not contribute significantly to mammarenavirus-host associations. Finally, we show that extremely strong selective pressure on the viral polymerase accompanied the speciation of NW viruses. These data suggest that the evolutionary history of mammarenaviruses was not driven by codivergence with their hosts. The viral polymerase should be regarded as a major determinant of mammarenavirus adaptation.}, } @article {pmid29608722, year = {2018}, author = {Pizzollo, J and Nielsen, WJ and Shibata, Y and Safi, A and Crawford, GE and Wray, GA and Babbitt, CC}, title = {Comparative Serum Challenges Show Divergent Patterns of Gene Expression and Open Chromatin in Human and Chimpanzee.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {826-839}, pmid = {29608722}, issn = {1759-6653}, support = {S10 OD018164/OD/NIH HHS/United States ; }, mesh = {Animals ; Chromatin/*genetics ; *Evolution, Molecular ; Gene Expression Regulation/genetics ; Genetic Variation/*genetics ; Humans ; Pan troglodytes/blood/genetics ; Promoter Regions, Genetic ; Regulatory Sequences, Nucleic Acid/*genetics ; Species Specificity ; Transcription Factors/genetics ; }, abstract = {Humans experience higher rates of age-associated diseases than our closest living evolutionary relatives, chimpanzees. Environmental factors can explain many of these increases in disease risk, but species-specific genetic changes can also play a role. Alleles that confer increased disease susceptibility later in life can persist in a population in the absence of selective pressure if those changes confer positive adaptation early in life. One age-associated disease that disproportionately affects humans compared with chimpanzees is epithelial cancer. Here, we explored genetic differences between humans and chimpanzees in a well-defined experimental assay that mimics gene expression changes that happen during cancer progression: A fibroblast serum challenge. We used this assay with fibroblasts isolated from humans and chimpanzees to explore species-specific differences in gene expression and chromatin state with RNA-Seq and DNase-Seq. Our data reveal that human fibroblasts increase expression of genes associated with wound healing and cancer pathways; in contrast, chimpanzee gene expression changes are not concentrated around particular functional categories. Chromatin accessibility dramatically increases in human fibroblasts, yet decreases in chimpanzee cells during the serum response. Many regions of opening and closing chromatin are in close proximity to genes encoding transcription factors or genes involved in wound healing processes, further supporting the link between changes in activity of regulatory elements and changes in gene expression. Together, these expression and open chromatin data show that humans and chimpanzees have dramatically different responses to the same physiological stressor, and how a core physiological process can evolve quickly over relatively short evolutionary time scales.}, } @article {pmid29608721, year = {2018}, author = {Mier, P and Andrade-Navarro, MA}, title = {Glutamine Codon Usage and polyQ Evolution in Primates Depend on the Q Stretch Length.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {816-825}, pmid = {29608721}, issn = {1759-6653}, mesh = {Animals ; Codon/*genetics ; *Evolution, Molecular ; Glutamine/*genetics ; Humans ; Peptides/*genetics ; Primates/genetics ; Proteome/genetics ; }, abstract = {Amino acid usage in a proteome depends mostly on its taxonomy, as it does the codon usage in transcriptomes. Here, we explore the level of variation in the codon usage of a specific amino acid, glutamine, in relation to the number of consecutive glutamine residues. We show that CAG triplets are consistently more abundant in short glutamine homorepeats (polyQ, four to eight residues) than in shorter glutamine stretches (one to three residues), leading to the evolutionary growth of the repeat region in a CAG-dependent manner. The length of orthologous polyQ regions is mostly stable in primates, particularly the short ones. Interestingly, given a short polyQ the CAG usage is higher in unstable-in-length orthologous polyQ regions. This indicates that CAG triplets produce the necessary instability for a glutamine stretch to grow. Proteins related to polyQ-associated diseases behave in a more extreme way, with longer glutamine stretches in human and evolutionarily closer nonhuman primates, and an overall higher CAG usage. In the light of our results, we suggest an evolutionary model to explain the glutamine codon usage in polyQ regions.}, } @article {pmid29608720, year = {2018}, author = {Gilbert, MJ and Duim, B and van der Graaf-van Bloois, L and Wagenaar, JA and Zomer, AL}, title = {Homologous Recombination between Genetically Divergent Campylobacter fetus Lineages Supports Host-Associated Speciation.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {716-722}, pmid = {29608720}, issn = {1759-6653}, mesh = {Animals ; Campylobacter Infections/*genetics/microbiology ; Campylobacter fetus/*genetics/pathogenicity ; Genetic Drift ; *Genetic Variation ; Genome, Bacterial/genetics ; Homologous Recombination/*genetics ; Mammals/embryology/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Reptiles/embryology/microbiology ; Species Specificity ; Whole Genome Sequencing ; }, abstract = {Homologous recombination is a major driver of bacterial speciation. Genetic divergence and host association are important factors influencing homologous recombination. Here, we study these factors for Campylobacter fetus, which shows a distinct intraspecific host dichotomy. Campylobacter fetus subspecies fetus (Cff) and venerealis are associated with mammals, whereas C. fetus subsp. testudinum (Cft) is associated with reptiles. Recombination between these genetically divergent C. fetus lineages is extremely rare. Previously it was impossible to show whether this barrier to recombination was determined by the differential host preferences, by the genetic divergence between both lineages or by other factors influencing recombination, such as restriction-modification, CRISPR/Cas, and transformation systems. Fortuitously, a distinct C. fetus lineage (ST69) was found, which was highly related to mammal-associated C. fetus, yet isolated from a chelonian. The whole genome sequences of two C. fetus ST69 isolates were compared with those of mammal- and reptile-associated C. fetus strains for phylogenetic and recombination analysis. In total, 5.1-5.5% of the core genome of both ST69 isolates showed signs of recombination. Of the predicted recombination regions, 80.4% were most closely related to Cft, 14.3% to Cff, and 5.6% to C. iguaniorum. Recombination from C. fetus ST69 to Cft was also detected, but to a lesser extent and only in chelonian-associated Cft strains. This study shows that despite substantial genetic divergence no absolute barrier to homologous recombination exists between two distinct C. fetus lineages when occurring in the same host type, which provides valuable insights in bacterial speciation and evolution.}, } @article {pmid29608719, year = {2018}, author = {Lavi, B and Levy Karin, E and Pupko, T and Hazkani-Covo, E}, title = {The Prevalence and Evolutionary Conservation of Inverted Repeats in Proteobacteria.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {918-927}, pmid = {29608719}, issn = {1759-6653}, mesh = {Conserved Sequence/*genetics ; Escherichia coli/genetics ; *Evolution, Molecular ; Genome, Bacterial/genetics ; Inverted Repeat Sequences/*genetics ; Proteobacteria/genetics ; }, abstract = {Perfect short inverted repeats (IRs) are known to be enriched in a variety of bacterial and eukaryotic genomes. Currently, it is unclear whether perfect IRs are conserved over evolutionary time scales. In this study, we aimed to characterize the prevalence and evolutionary conservation of IRs across 20 proteobacterial strains. We first identified IRs in Escherichia coli K-12 substr MG1655 and showed that they are overabundant. We next aimed to test whether this overabundance is reflected in the conservation of IRs over evolutionary time scales. To this end, for each perfect IR identified in E. coli MG1655, we collected orthologous sequences from related proteobacterial genomes. We next quantified the evolutionary conservation of these IRs, that is, the presence of the exact same IR across orthologous regions. We observed high conservation of perfect IRs: out of the 234 examined orthologous regions, 145 were more conserved than expected, which is statistically significant even after correcting for multiple testing. Our results together with previous experimental findings support a model in which imperfect IRs are corrected to perfect IRs in a preferential manner via a template switching mechanism.}, } @article {pmid29608718, year = {2018}, author = {Subramanian, S}, title = {Influence of Effective Population Size on Genes under Varying Levels of Selection Pressure.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {756-762}, pmid = {29608718}, issn = {1759-6653}, mesh = {Amino Acid Substitution/genetics ; Animals ; Gene Expression/genetics ; *Genetics, Population ; Mice ; *Population Density ; *Selection, Genetic ; }, abstract = {The ratio of diversities at amino acid changing (nonsynonymous) and neutral (synonymous) sites (ω = πN/πS) is routinely used to measure the intensity of selection pressure. It is well known that this ratio is influenced by the effective population size (Ne) and selection coefficient (s). Here, we examined the effects of effective population size on ω by comparing protein-coding genes from Mus musculus castaneus and Mus musculus musculus-two mouse subspecies with different Ne. Our results revealed a positive relationship between the magnitude of selection intensity and the ω estimated for genes. For genes under high selective constraints, the ω estimated for the subspecies with small Ne (M. m. musculus) was three times higher than that observed for that with large Ne (M. m. castaneus). However, this difference was only 18% for genes under relaxed selective constraints. We showed that the observed relationship is qualitatively similar to the theoretical predictions. We also showed that, for highly expressed genes, the ω of M. m. musculus was 2.1 times higher than that of M.m. castaneus and this difference was only 27% for genes with low expression levels. These results suggest that the effect of effective population size is more pronounced in genes under high purifying selection. Hence the choice of genes is important when ω is used to infer the effective size of a population.}, } @article {pmid29608717, year = {2018}, author = {Furman, BLS and Evans, BJ}, title = {Divergent Evolutionary Trajectories of Two Young, Homomorphic, and Closely Related Sex Chromosome Systems.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {742-755}, pmid = {29608717}, issn = {1759-6653}, mesh = {Animals ; *Biological Evolution ; Female ; Genetic Variation/genetics ; Genome ; Male ; Sex Chromosomes/*genetics ; Sex Determination Processes/*genetics ; Xenopus laevis/genetics/growth & development ; }, abstract = {There exists extraordinary variation among species in the degree and nature of sex chromosome divergence. However, much of our knowledge about sex chromosomes is based on comparisons between deeply diverged species with different ancestral sex chromosomes, making it difficult to establish how fast and why sex chromosomes acquire variable levels of divergence. To address this problem, we studied sex chromosome evolution in two species of African clawed frog (Xenopus), both of whom acquired novel systems for sex determination from a recent common ancestor, and both of whom have female (ZW/ZZ) heterogamy. Derived sex chromosomes of one species, X. laevis, have a small region of suppressed recombination that surrounds the sex determining locus, and have remained this way for millions of years. In the other species, X. borealis, a younger sex chromosome system exists on a different pair of chromosomes, but the region of suppressed recombination surrounding an unidentified sex determining gene is vast, spanning almost half of the sex chromosomes. Differences between these sex chromosome systems are also apparent in the extent of nucleotide divergence between the sex chromosomes carried by females. Our analyses also indicate that in autosomes of both of these species, recombination during oogenesis occurs more frequently and in different genomic locations than during spermatogenesis. These results demonstrate that new sex chromosomes can assume radically different evolutionary trajectories, with far-reaching genomic consequences. They also suggest that in some instances the origin of new triggers for sex determination may be coupled with rapid evolution sex chromosomes, including recombination suppression of large genomic regions.}, } @article {pmid29608716, year = {2018}, author = {Roessler, K and Bousios, A and Meca, E and Gaut, BS}, title = {Modeling Interactions between Transposable Elements and the Plant Epigenetic Response: A Surprising Reliance on Element Retention.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {803-815}, pmid = {29608716}, issn = {1759-6653}, support = {T32 EB009418/EB/NIBIB NIH HHS/United States ; }, mesh = {Arabidopsis/*genetics ; DNA Methylation/genetics ; DNA Transposable Elements/*genetics ; Epigenesis, Genetic/*genetics ; Gene Expression Regulation, Plant ; Gene Silencing ; Genome, Plant/*genetics ; RNA, Messenger/genetics ; RNA, Small Interfering/genetics ; }, abstract = {Transposable elements (TEs) compose the majority of angiosperm DNA. Plants counteract TE activity by silencing them epigenetically. One form of epigenetic silencing requires 21-22 nt small interfering RNAs that act to degrade TE mRNA and may also trigger DNA methylation. DNA methylation is reinforced by a second mechanism, the RNA-dependent DNA methylation (RdDM) pathway. RdDM relies on 24 nt small interfering RNAs and ultimately establishes TEs in a quiescent state. These host factors interact at a systems level, but there have been no system level analyses of their interactions. Here, we define a deterministic model that represents the propagation of active TEs, aspects of the host response and the accumulation of silenced TEs. We describe general properties of the model and also fit it to biological data in order to explore two questions. The first is why two overlapping pathways are maintained, given that both are likely energetically expensive. Under our model, RdDM silenced TEs effectively even when the initiation of silencing was weak. This relationship implies that only a small amount of RNAi is needed to initiate TE silencing, but reinforcement by RdDM is necessary to efficiently counter TE propagation. Second, we investigated the reliance of the host response on rates of TE deletion. The model predicted that low levels of deletion lead to few active TEs, suggesting that silencing is most efficient when methylated TEs are retained in the genome, thereby providing one explanation for the large size of plant genomes.}, } @article {pmid29608715, year = {2018}, author = {Gul, IS and Staal, J and Hulpiau, P and De Keuckelaere, E and Kamm, K and Deroo, T and Sanders, E and Staes, K and Driege, Y and Saeys, Y and Beyaert, R and Technau, U and Schierwater, B and van Roy, F}, title = {GC Content of Early Metazoan Genes and Its Impact on Gene Expression Levels in Mammalian Cell Lines.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {909-917}, pmid = {29608715}, issn = {1759-6653}, mesh = {Animals ; Cell Line ; *Evolution, Molecular ; Humans ; Mammals/*genetics ; *Phylogeny ; Proteins/*genetics ; }, abstract = {With the genomes available for many animal clades, including the early-branching metazoans, one can readily study the functional conservation of genes across a diversity of animal lineages. Ectopic expression of an animal protein in, for instance, a mammalian cell line is a generally used strategy in structure-function analysis. However, this might turn out to be problematic in case of distantly related species. Here we analyzed the GC content of the coding sequences of basal animals and show its impact on gene expression levels in human cell lines, and, importantly, how this expression efficiency can be improved. Optimization of the GC3 content in the coding sequences of cadherin, alpha-catenin, and paracaspase of Trichoplax adhaerens dramatically increased the expression of these basal animal genes in human cell lines.}, } @article {pmid29608184, year = {2018}, author = {}, title = {Corrigendum.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3570}, doi = {10.1002/ece3.3974}, pmid = {29608184}, issn = {2045-7758}, abstract = {[This corrects the article DOI: 10.1002/ece3.3398.].}, } @article {pmid29607046, year = {2018}, author = {Shoemaker, KT and Heffelfinger, LJ and Jackson, NJ and Blum, ME and Wasley, T and Stewart, KM}, title = {A machine-learning approach for extending classical wildlife resource selection analyses.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3556-3569}, pmid = {29607046}, issn = {2045-7758}, abstract = {Resource selection functions (RSFs) are tremendously valuable for ecologists and resource managers because they quantify spatial patterns in resource utilization by wildlife, thereby facilitating identification of critical habitat areas and characterizing specific habitat features that are selected or avoided. RSFs discriminate between known-use resource units (e.g., telemetry locations) and available (or randomly selected) resource units based on an array of environmental features, and in their standard form are performed using logistic regression. As generalized linear models, standard RSFs have some notable limitations, such as difficulties in accommodating nonlinear (e.g., humped or threshold) relationships and complex interactions. Increasingly, ecologists are using flexible machine-learning methods (e.g., random forests, neural networks) to overcome these limitations. Herein, we investigate the seasonal resource selection patterns of mule deer (Odocoileus hemionus) by comparing a logistic regression framework with random forest (RF), a popular machine-learning algorithm. Random forest (RF) models detected nonlinear relationships (e.g., optimal ranges for slope and elevation) and complex interactions which would have been very challenging to discover and characterize using standard model-based approaches. Compared with standard RSF models, RF models exhibited improved predictive skill, provided novel insights about resource selection patterns of mule deer, and, when projected across a relevant geographic space, manifested notable differences in predicted habitat suitability. We recommend that wildlife researchers harness the strengths of machine-learning tools like RF in addition to "classical" tools (e.g., mixed-effects logistic regression) for evaluating resource selection, especially in cases where extensive telemetry data sets are available.}, } @article {pmid29607045, year = {2018}, author = {Hatase, H and Omuta, K and Itou, K and Komatsu, T}, title = {Effect of maternal foraging habitat on offspring quality in the loggerhead sea turtle (Caretta caretta).}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3543-3555}, pmid = {29607045}, issn = {2045-7758}, abstract = {Exploring a trade-off between quantity and quality of offspring allows differences in the fitness between alternative life histories to be accurately evaluated. We addressed the mechanism that maintains alternative life histories (small oceanic planktivores vs. large neritic benthivores) observed in a loggerhead sea turtle (Caretta caretta) population, which has been suggested to be environmental, based on the lack of genetic structure and a large difference in reproductive output. We examined whether maternal foraging habitat affects offspring quality, by measuring the morphology, emergence success, and righting response of hatchlings following incubation in a common open sand area over the whole nesting season at Yakushima Island, Japan, and by recording early growth and survival of offspring that were reared in a common environment at a Japanese aquarium. Furthermore, we tested whether sea turtles adjust egg size in response to temporal shifts of the incubation environment. There were no significant differences in any hatchling traits between oceanic and neritic foragers (which were classified by stable isotope ratios), except for clutches laid during the warmest period of the nesting season. There were also no significant differences in the growth and survival of offspring originating from the two foragers. The size of eggs from both foragers significantly increased as the season progressed, even though the rookery had heavy rainfall, negating the need to counteract heat-related reduction in hatchling morphology. In comparison, the sizes of adult body and clutches from both foragers did not vary significantly. The results further support our previous suggestions that the size-related foraging dichotomy exhibited by adult sea turtles does not have a genetic basis, but derives from phenotypic plasticity. Adjustment in reproductive investment may be associated with: (1) predation avoidance, (2) founder effect, and/or (3) annual variation in egg size.}, } @article {pmid29607044, year = {2018}, author = {Margaryan, A and Hansen, HB and Rasmussen, S and Sikora, M and Moiseyev, V and Khoklov, A and Epimakhov, A and Yepiskoposyan, L and Kriiska, A and Varul, L and Saag, L and Lynnerup, N and Willerslev, E and Allentoft, ME}, title = {Ancient pathogen DNA in human teeth and petrous bones.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3534-3542}, pmid = {29607044}, issn = {2045-7758}, abstract = {Recent ancient DNA (aDNA) studies of human pathogens have provided invaluable insights into their evolutionary history and prevalence in space and time. Most of these studies were based on DNA extracted from teeth or postcranial bones. In contrast, no pathogen DNA has been reported from the petrous bone which has become the most desired skeletal element in ancient DNA research due to its high endogenous DNA content. To compare the potential for pathogenic aDNA retrieval from teeth and petrous bones, we sampled these elements from five ancient skeletons, previously shown to be carrying Yersinia pestis. Based on shotgun sequencing data, four of these five plague victims showed clearly detectable levels of Y. pestis DNA in the teeth, whereas all the petrous bones failed to produce Y. pestis DNA above baseline levels. A broader comparative metagenomic analysis of teeth and petrous bones from 10 historical skeletons corroborated these results, showing a much higher microbial diversity in teeth than petrous bones, including pathogenic and oral microbial taxa. Our results imply that although petrous bones are highly valuable for ancient genomic analyses as an excellent source of endogenous DNA, the metagenomic potential of these dense skeletal elements is highly limited. This trade-off must be considered when designing the sampling strategy for an aDNA project.}, } @article {pmid29607043, year = {2018}, author = {Tuomisto, H and Tuomisto, M and Tuomisto, JT}, title = {How scientists perceive the evolutionary origin of human traits: Results of a survey study.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3518-3533}, pmid = {29607043}, issn = {2045-7758}, abstract = {Various hypotheses have been proposed for why the traits distinguishing humans from other primates originally evolved, and any given trait may have been explained both as an adaptation to different environments and as a result of demands from social organization or sexual selection. To find out how popular the different explanations are among scientists, we carried out an online survey among authors of recent scientific papers in journals covering relevant fields of science (paleoanthropology, paleontology, ecology, evolution, human biology). Some of the hypotheses were clearly more popular among the 1,266 respondents than others, but none was universally accepted or rejected. Even the most popular of the hypotheses were assessed "very likely" by <50% of the respondents, but many traits had 1-3 hypotheses that were found at least moderately likely by >70% of the respondents. An ordination of the hypotheses identified two strong gradients. Along one gradient, the hypotheses were sorted by their popularity, measured by the average credibility score given by the respondents. The second gradient separated all hypotheses postulating adaptation to swimming or diving into their own group. The average credibility scores given for different subgroups of the hypotheses were not related to respondent's age or number of publications authored. However, (paleo)anthropologists were more critical of all hypotheses, and much more critical of the water-related ones, than were respondents representing other fields of expertise. Although most respondents did not find the water-related hypotheses likely, only a small minority found them unscientific. The most popular hypotheses were based on inherent drivers; that is, they assumed the evolution of a trait to have been triggered by the prior emergence of another human-specific behavioral or morphological trait, but opinions differed as to which of the traits came first.}, } @article {pmid29607042, year = {2018}, author = {Groot, MP and Wagemaker, N and Ouborg, NJ and Verhoeven, KJF and Vergeer, P}, title = {Epigenetic population differentiation in field- and common garden-grown Scabiosa columbaria plants.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3505-3517}, pmid = {29607042}, issn = {2045-7758}, abstract = {Populations often differ in phenotype and these differences can be caused by adaptation by natural selection, random neutral processes, and environmental responses. The most straightforward way to divide mechanisms that influence phenotypic variation is heritable variation and environmental-induced variation (e.g., plasticity). While genetic variation is responsible for most heritable phenotypic variation, part of this is also caused by nongenetic inheritance. Epigenetic processes may be one of the underlying mechanisms of plasticity and nongenetic inheritance and can therefore possibly contribute to heritable differences through drift and selection. Epigenetic variation may be influenced directly by the environment, and part of this variation can be transmitted to next generations. Field screenings combined with common garden experiments will add valuable insights into epigenetic differentiation, epigenetic memory and can help to reveal part of the relative importance of epigenetics in explaining trait variation. We explored both genetic and epigenetic diversity, structure and differentiation in the field and a common garden for five British and five French Scabiosa columbaria populations. Genetic and epigenetic variation was subsequently correlated with trait variation. Populations showed significant epigenetic differentiation between populations and countries in the field, but also when grown in a common garden. By comparing the epigenetic variation between field and common garden-grown plants, we showed that a considerable part of the epigenetic memory differed from the field-grown plants and was presumably environmentally induced. The memory component can consist of heritable variation in methylation that is not sensitive to environments and possibly genetically based, or environmentally induced variation that is heritable, or a combination of both. Additionally, random epimutations might be responsible for some differences as well. By comparing epigenetic variation in both the field and common environment, our study provides useful insight into the environmental and genetic components of epigenetic variation.}, } @article {pmid29607041, year = {2018}, author = {Francisco, PM and Mori, GM and Alves, FM and Tambarussi, EV and de Souza, AP}, title = {Population genetic structure, introgression, and hybridization in the genus Rhizophora along the Brazilian coast.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3491-3504}, pmid = {29607041}, issn = {2045-7758}, abstract = {Mangrove plants comprise plants with similar ecological features that have enabled them to adapt to life between the sea and the land. Within a geographic region, different mangrove species share not only similar adaptations but also similar genetic structure patterns. Along the eastern coast of South America, there is a subdivision between the populations north and south of the continent's northeastern extremity. Here, we aimed to test for this north-south genetic structure in Rhizophora mangle, a dominant mangrove plant in the Western Hemisphere. Additionally, we aimed to study the relationships between R. mangle, R. racemosa, and R. × harrisonii and to test for evidence of hybridization and introgression. Our results confirmed the north-south genetic structure pattern in R. mangle and revealed a less abrupt genetic break in the northern population than those observed in Avicennia species, another dominant and widespread mangrove genus in the Western Hemisphere. These results are consistent with the role of oceanic currents influencing sea-dispersed plants and differences between Avicennia and Rhizophora propagules in longevity and establishment time. We also observed that introgression and hybridization are relevant biological processes in the northeastern coast of South America and that they are likely asymmetric toward R. mangle, suggesting that adaptation might be a process maintaining this hybrid zone.}, } @article {pmid29607040, year = {2018}, author = {Tinoco, BA and Santillán, VE and Graham, CH}, title = {Land use change has stronger effects on functional diversity than taxonomic diversity in tropical Andean hummingbirds.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3478-3490}, pmid = {29607040}, issn = {2045-7758}, abstract = {Land use change modifies the environment at multiple spatial scales, and is a main driver of species declines and deterioration of ecosystem services. However, most of the research on the effects of land use change has focused on taxonomic diversity, while functional diversity, an important predictor of ecosystem services, is often neglected. We explored how local and landscape scale characteristics influence functional and taxonomic diversity of hummingbirds in the Andes Mountains in southern Ecuador. Data was collected in six landscapes along a land use gradient, from an almost intact landscape to one dominated by cattle pastures. We used point counts to sample hummingbirds from 2011 to 2012 to assessed how local factors (i.e., vegetation structure, flowering plants richness, nectar availability) and landscape factors (i.e., landscape heterogeneity, native vegetation cover) influenced taxonomic and functional diversity. Then, we analyzed environment - trait relationships (RLQ test) to explore how different hummingbird functional traits influenced species responses to these factors. Taxonomic and functional diversity of hummingbirds were positively associated with landscape heterogeneity but only functional diversity was positively related to native vegetation coverage. We found a weak response of taxonomic and functional diversity to land use change at the local scale. Environment-trait associations showed that body mass of hummingbirds likely influenced species sensitivity to land use change. In conclusion, landscape heterogeneity created by land use change can positively influence hummingbird taxonomic and functional diversity; however, a reduction of native vegetation cover could decrease functional diversity. Given that functional diversity can mediate ecosystem services, the conservation of native vegetation cover could play a key role in the maintenance of hummingbird pollination services in the tropical Andes. Moreover, there are particular functional traits, such as body mass, that increase a species sensitivity to land use change.}, } @article {pmid29607039, year = {2018}, author = {Chambert, T and Pilliod, DS and Goldberg, CS and Doi, H and Takahara, T}, title = {An analytical framework for estimating aquatic species density from environmental DNA.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3468-3477}, pmid = {29607039}, issn = {2045-7758}, abstract = {Environmental DNA (eDNA) analysis of water samples is on the brink of becoming a standard monitoring method for aquatic species. This method has improved detection rates over conventional survey methods and thus has demonstrated effectiveness for estimation of site occupancy and species distribution. The frontier of eDNA applications, however, is to infer species density. Building upon previous studies, we present and assess a modeling approach that aims at inferring animal density from eDNA. The modeling combines eDNA and animal count data from a subset of sites to estimate species density (and associated uncertainties) at other sites where only eDNA data are available. As a proof of concept, we first perform a cross-validation study using experimental data on carp in mesocosms. In these data, fish densities are known without error, which allows us to test the performance of the method with known data. We then evaluate the model using field data from a study on a stream salamander species to assess the potential of this method to work in natural settings, where density can never be known with absolute certainty. Two alternative distributions (Normal and Negative Binomial) to model variability in eDNA concentration data are assessed. Assessment based on the proof of concept data (carp) revealed that the Negative Binomial model provided much more accurate estimates than the model based on a Normal distribution, likely because eDNA data tend to be overdispersed. Greater imprecision was found when we applied the method to the field data, but the Negative Binomial model still provided useful density estimates. We call for further model development in this direction, as well as further research targeted at sampling design optimization. It will be important to assess these approaches on a broad range of study systems.}, } @article {pmid29607038, year = {2018}, author = {Alagador, D and Cerdeira, JO}, title = {A quantitative analysis on the effects of critical factors limiting the effectiveness of species conservation in future time.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3457-3467}, pmid = {29607038}, issn = {2045-7758}, abstract = {The effectiveness of conservation plans depends on environmental, ecological, and socioeconomic factors. Global change makes conservation decisions even more challenging. Among others, the components of most concern in modern-day conservation assessments are as follows: the magnitude of climate and land-use changes; species dispersal abilities; competition with harmful socioeconomic activities for land use; the number of threatened species to consider; and, relatedly, the available budget to act. Here, we provide a unified framework that quantifies the relative effects of those factors on conservation. We conducted an area-scheduling work plan in order to identify sets of areas along time in which the persistence expectancies of species are optimized. The approach was illustrated using data of potential distribution of ten nonvolant mammal species in Iberia Peninsula from current time up to 2080. Analyses were conducted considering possible setups among the factors that are likely to critically impact conservation success: three climate/land-use scenarios; four species' dispersal kernel curves; six land-use layer types; and two planning designs, in which assessments were made independently for each species, or joining all species in a single plan. We identified areas for an array of investments levels capable to circumvent the spatial conflicts with socioeconomic activities. The effect of each factor on the estimated species persistence scores was assessed using linear mixed models. Our results evidence that conservation success is highly reliant on the resources available to abate land-use conflicts. Nonetheless, under the same investment levels, planning design and climate change were the factors that most shaped species persistence scores. The persistence of five species was especially affected by the sole effect of planning design and consequently, larger conservation investments may retard climatic debts. For three species, the negative effects of a changing climate and of multiple-species planning designs added up, making these species especially at risk. Integrated assessments of the factors most likely to limit species persistence are pivotal to achieve effectiveness.}, } @article {pmid29607037, year = {2018}, author = {Descamps, C and Quinet, M and Baijot, A and Jacquemart, AL}, title = {Temperature and water stress affect plant-pollinator interactions in Borago officinalis (Boraginaceae).}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3443-3456}, pmid = {29607037}, issn = {2045-7758}, abstract = {Climate change alters the abiotic constraints faced by plants, including increasing temperature and water stress. These changes may affect flower development and production of flower rewards, thus altering plant-pollinator interactions. Here, we investigated the consequences of increased temperature and water stress on plant growth, floral biology, flower-reward production, and insect visitation of a widespread bee-visited species, Borago officinalis. Plants were grown for 5 weeks under three temperature regimes (21, 24, and 27°C) and two watering regimes (well-watered and water-stressed). Plant growth was more affected by temperature rise than water stress, and the reproductive growth was affected by both stresses. Vegetative traits were stimulated at 24°C, but impaired at 27°C. Flower development was mainly affected by water stress, which decreased flower number (15 ± 2 flowers/plant in well-watered plants vs. 8 ± 1 flowers/plant under water stress). Flowers had a reduced corolla surface under temperature rise and water stress (3.8 ± 0.5 cm2 in well-watered plants at 21°C vs. 2.2 ± 0.1 cm2 in water-stressed plants at 27°C). Both constraints reduced flower-reward production. Nectar sugar content decreased from 3.9 ± 0.3 mg/flower in the well-watered plants at 21°C to 1.3 ± 0.4 mg/flower in the water-stressed plants at 27°C. Total pollen quantity was not affected, but pollen viability decreased from 79 ± 4% in the well-watered plants at 21°C to 25 ± 9% in the water-stressed plants at 27°C. Flowers in the well-watered plants at 21°C received at least twice as many bumblebee visits compared with the other treatments. In conclusion, floral modifications induced by abiotic stresses related to climate change affect insect behavior and alter plant-pollinator interactions.}, } @article {pmid29607036, year = {2018}, author = {Vieira, EA and Flores, AAV and Dias, GM}, title = {Persistence and space preemption explain species-specific founder effects on the organization of marine sessile communities.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3430-3442}, pmid = {29607036}, issn = {2045-7758}, abstract = {Community assembly may not follow predictable successional stages, with a large fraction of the species pool constituted by potential pioneering species and successful founders defined through lottery. In such systems, priority effects may be relevant in the determination of trajectories of developing communities and hence diversity and assemblage structure at later advanced states. In order to assess how different founder species may trigger variable community trajectories and structures, we conducted an experimental study using subtidal sessile assemblages as model. We manipulated the identity of functionally different founders and initial colony size (a proxy of the time lag before the arrival of later species), and followed trajectories. We did not observe any effects of colony size on response variables, suggesting that priority effects take place even when the time lag between the establishment of pioneering species and late colonizers is very short. Late community structure at experimental panels that started either with the colonial ascidian Botrylloides nigrum, or the arborescent bryozoan Bugula neritina, was similar to control panels allowed natural assembling. In spite of high potential for fast space domination, and hence negative priority effects, B. nigrum suffered high mortality and did not persist throughout succession. Bugula neritina provided complex physical microhabitats through conspecific clustering that have enhanced larval settlement of late species arrivals, but no apparent facilitation was observed. Differently, panels founded by the encrusting bryozoan Schizoporella errata led to different and less diverse communities compared to naturally assembled panels, evidencing strong negative priority effects through higher persistence and space preemption. Schizoporella errata founder colonies inhibited further conspecific settlement, which may greatly relax intraspecific competition, allowing resource allocation to colony growth and space domination, thus reducing the chances for the establishment of other species.}, } @article {pmid29607035, year = {2018}, author = {Reichert, MS and Höbel, G}, title = {Phenotypic integration and the evolution of signal repertoires: A case study of treefrog acoustic communication.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3410-3429}, pmid = {29607035}, issn = {2045-7758}, abstract = {Animal signals are inherently complex phenotypes with many interacting parts combining to elicit responses from receivers. The pattern of interrelationships between signal components reflects the extent to which each component is expressed, and responds to selection, either in concert with or independently of others. Furthermore, many species have complex repertoires consisting of multiple signal types used in different contexts, and common morphological and physiological constraints may result in interrelationships extending across the multiple signals in species' repertoires. The evolutionary significance of interrelationships between signal traits can be explored within the framework of phenotypic integration, which offers a suite of quantitative techniques to characterize complex phenotypes. In particular, these techniques allow for the assessment of modularity and integration, which describe, respectively, the extent to which sets of traits covary either independently or jointly. Although signal and repertoire complexity are thought to be major drivers of diversification and social evolution, few studies have explicitly measured the phenotypic integration of signals to investigate the evolution of diverse communication systems. We applied methods from phenotypic integration studies to quantify integration in the two primary vocalization types (advertisement and aggressive calls) in the treefrogs Hyla versicolor, Hyla cinerea, and Dendropsophus ebraccatus. We recorded male calls and calculated standardized phenotypic variance-covariance (P) matrices for characteristics within and across call types. We found significant integration across call types, but the strength of integration varied by species and corresponded with the acoustic similarity of the call types within each species. H. versicolor had the most modular advertisement and aggressive calls and the least acoustically similar call types. Additionally, P was robust to changing social competition levels in H. versicolor. Our findings suggest new directions in animal communication research in which the complex relationships among the traits of multiple signals are a key consideration for understanding signal evolution.}, } @article {pmid29607034, year = {2018}, author = {Kakouei, K and Kiesel, J and Domisch, S and Irving, KS and Jähnig, SC and Kail, J}, title = {Projected effects of Climate-change-induced flow alterations on stream macroinvertebrate abundances.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3393-3409}, pmid = {29607034}, issn = {2045-7758}, abstract = {Global change has the potential to affect river flow conditions which are fundamental determinants of physical habitats. Predictions of the effects of flow alterations on aquatic biota have mostly been assessed based on species ecological traits (e.g., current preferences), which are difficult to link to quantitative discharge data. Alternatively, we used empirically derived predictive relationships for species' response to flow to assess the effect of flow alterations due to climate change in two contrasting central European river catchments. Predictive relationships were set up for 294 individual species based on (1) abundance data from 223 sampling sites in the Kinzig lower-mountainous catchment and 67 sites in the Treene lowland catchment, and (2) flow conditions at these sites described by five flow metrics quantifying the duration, frequency, magnitude, timing and rate of flow events using present-day gauging data. Species' abundances were predicted for three periods: (1) baseline (1998-2017), (2) horizon 2050 (2046-2065) and (3) horizon 2090 (2080-2099) based on these empirical relationships and using high-resolution modeled discharge data for the present and future climate conditions. We compared the differences in predicted abundances among periods for individual species at each site, where the percent change served as a proxy to assess the potential species responses to flow alterations. Climate change was predicted to most strongly affect the low-flow conditions, leading to decreased abundances of species up to -42%. Finally combining the response of all species over all metrics indicated increasing overall species assemblage responses in 98% of the studied river reaches in both projected horizons and were significantly larger in the lower-mountainous Kinzig compared to the lowland Treene catchment. Such quantitative analyses of freshwater taxa responses to flow alterations provide valuable tools for predicting potential climate-change impacts on species abundances and can be applied to any stressor, species, or region.}, } @article {pmid29607033, year = {2018}, author = {Comay, O and Dayan, T}, title = {What determines prey selection in owls? Roles of prey traits, prey class, environmental variables, and taxonomic specialization.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3382-3392}, pmid = {29607033}, issn = {2045-7758}, abstract = {Ecological theory suggests that prey size should increase with predator size, but this trend may be masked by other factors affecting prey selection, such as environmental constraints or specific prey preferences of predator species. Owls are an ideal case study for exploring how predator body size affects prey selection in the presence of other factors due to the ease of analyzing their diets from owl pellets and their widespread distributions, allowing interspecific comparisons between variable habitats. Here, we analyze various dimensions of prey resource selection among owls, including prey size, taxonomy (i.e., whether or not particular taxa are favored regardless of their size), and prey traits (movement type, social structure, activity pattern, and diet). We collected pellets of five sympatric owl species (Athene noctua, Tyto alba, Asio otus, Strix aluco, and Bubo bubo) from 78 sites across the Mediterranean Levant. Prey intake was compared between sites, with various environmental variables and owl species as predictors of abundance. Despite significant environmental impacts on prey intake, some key patterns emerge among owl species studied. Owls select prey by predator body size: Larger owls tend to feed on wider ranges of prey sizes, leading to higher means. In addition, guild members show both specialization and generalism in terms of prey taxa, sometimes in contrast with the expectations of the predator-prey body size hypothesis. Our results suggest that while predator body size is an important factor in prey selection, taxon specialization by predator species also has considerable impact.}, } @article {pmid29607032, year = {2018}, author = {Mukai, H and Hironaka, M and Tojo, S and Nomakuchi, S}, title = {Maternal hatching synchronization in a subsocial burrower bug mitigates the risk of future sibling cannibalism.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3376-3381}, pmid = {29607032}, issn = {2045-7758}, abstract = {Sibling cannibalism-the killing and consumption of conspecifics within broods-carries a high risk of direct and inclusive fitness loss for parents and offspring. We reported previously that a unique vibrational behavior shown by the mother of the subsocial burrower bug, Adomerus rotundus (Heteroptera: Cydnidae), induced synchronous hatching. Maternal regulation may be one of the most effective mechanisms for preventing or limiting sibling cannibalism. Here, we tested the hypothesis that synchronous hatching induced by maternal vibration in A. rotundus prevents sibling cannibalism. Mothers and their mature egg masses were allocated to three groups: synchronous hatching by maternal vibration (SHmv), synchronous hatching by artificial vibration (SHav), and asynchronous hatching (AH). We then investigated the influence of each hatching strategy on the occurrence of sibling cannibalism of eggs and early-instar nymphs in the laboratory. No difference in the proportion of eggs cannibalized was observed among the three groups. However, the proportion of nymphs cannibalized was higher in the AH group than in the SHmv group. The difference in the number of days to first molting within clutch was significantly higher in the AH group than in the SHmv group. Junior nymphs were sometimes eaten by senior nymphs. However, immediately after molting, senior nymphs were at a high risk of being eaten by junior nymphs. Our results indicate that synchronous hatching of A. rotundus is necessary to mitigate the risk of sibling cannibalism.}, } @article {pmid29607031, year = {2018}, author = {Wang, P and Shu, M and Mou, P and Weiner, J}, title = {Fine root responses to temporal nutrient heterogeneity and competition in seedlings of two tree species with different rooting strategies.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3367-3375}, pmid = {29607031}, issn = {2045-7758}, abstract = {There is little direct evidence for effects of soil heterogeneity and root plasticity on the competitive interactions among plants. In this study, we experimentally examined the impacts of temporal nutrient heterogeneity on root growth and interactions between two plant species with very different rooting strategies: Liquidambar styraciflua (sweet gum), which shows high root plasticity in response to soil nutrient heterogeneity, and Pinus taeda (loblolly pine), a species with less plastic roots. Seedlings of the two species were grown in sandboxes in inter- and intraspecific combinations. Nutrients were applied in a patch either in a stable (slow-release) or in a variable (pulse) manner. Plant aboveground biomass, fine root mass, root allocation between nutrient patch and outside the patch, and root vertical distribution were measured. L. styraciflua grew more aboveground (40% and 27% in stable and variable nutrient treatment, respectively) and fine roots (41% and 8% in stable and variable nutrient treatment, respectively) when competing with P. taeda than when competing with a conspecific individual, but the growth of P. taeda was not changed by competition from L. styraciflua. Temporal variation in patch nutrient level had little effect on the species' competitive interactions. The more flexible L. styraciflua changed its vertical distribution of fine roots in response to competition from P. taeda, growing more roots in deeper soil layers compared to its roots in conspecific competition, leading to niche differentiation between the species, while the fine root distribution of P. taeda remained unchanged across all treatments. Synthesis. L. styraciflua showed greater flexibility in root growth by changing its root vertical distribution and occupying space of not occupied by P. taeda. This flexibility gave L. styraciflua an advantage in interspecific competition.}, } @article {pmid29607030, year = {2018}, author = {Heffelfinger, LJ and Stewart, KM and Bush, AP and Sedinger, JS and Darby, NW and Bleich, VC}, title = {Timing of precipitation in an arid environment: Effects on population performance of a large herbivore.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3354-3366}, pmid = {29607030}, issn = {2045-7758}, abstract = {Climate models predict that shifts in temperature and precipitation patterns are likely to occur across the globe. Changing climate will likely have strong effects on arid environments as a result of increased temperatures, increasing frequency and intensity of droughts, and less consistent pulses of rainfall. Therefore, understanding the link between patterns of precipitation, temperature, and population performance of species occupying these environments will continue to increase in importance as climatic shifts occur within these natural ecosystems. We sought to evaluate how individual, maternal, population, and environmental, particularly temperature and precipitation, level factors influence population performance of a large herbivore in an arid environment. We used mule deer (Odocoileus hemionus) as a representative species and quantified juvenile survival to test hypotheses about effects of environmental factors on population performance. Precipitation events occurring in mid- to late-pregnancy (January-April) leading to spring green-up, as indexed by normalized difference in vegetation index, had the strongest positive effect on juvenile survival and recruitment. In addition, larger neonates had an increased probability of survival. Our findings indicate that timing and amount of precipitation prior to parturition have strong influences on maternal nutritional condition, which was passed on to young. These results have important implications for understanding how animal populations may benefit from timing of precipitation during spring and prior to parturition, especially in arid environments.}, } @article {pmid29607029, year = {2018}, author = {Fortin, M and Debenest, C and Souty-Grosset, C and Richard, FJ}, title = {Males prefer virgin females, even if parasitized, in the terrestrial isopod Armadillidium vulgare.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3341-3353}, pmid = {29607029}, issn = {2045-7758}, abstract = {In many species, males increase their reproductive success by choosing high-quality females. In natural populations, they interact with both virgin and mated females, which can store sperm in their spermatheca. Therefore, males elaborate strategies to avoid sperm competition. In the terrestrial isopod Armadillidium vulgare, females can store sperm and produce several clutches. Moreover, this species can be parasitized by Wolbachia, which feminizes genetic males, transforming them into functional females. Our study compared attractiveness and mate choice when a male is exposed to both virgin and experienced females (i.e., females who have produced offspring and rested for 6 months), with or without Wolbachia. Our results revealed that males are more attracted to virgin females than experienced females, even if these virgin females are parasitized. Moreover, the chemical analysis highlighted different odors in females according to their reproductive and infection (Wolbachia-free or vertically Wolbachia-infected) status. Males attempted copulation more frequently and for longer with virgin females, even if Wolbachia-infected, while experienced females refused further copulation. The evolutionary consequences of both male choice and female resistance on their fitness are discussed in this study.}, } @article {pmid29607028, year = {2018}, author = {Sparkman, AM and Chism, KR and Bronikowski, AM and Brummett, LJ and Combrink, LL and Davis, CL and Holden, KG and Kabey, NM and Miller, DAW}, title = {Use of field-portable ultrasonography reveals differences in developmental phenology and maternal egg provisioning in two sympatric viviparous snakes.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3330-3340}, pmid = {29607028}, issn = {2045-7758}, abstract = {A thorough understanding of the life cycles underlying the demography of wild species is limited by the difficulty of observing hidden life-history traits, such as embryonic development. Major aspects of embryonic development, such as the rate and timing of development, and maternal-fetal interactions can be critical features of early-life fitness and may impact population trends via effects on individual survival. While information on development in wild snakes and lizards is particularly limited, the repeated evolution of viviparity and diversity of reproductive mode in this clade make it a valuable subject of study. We used field-portable ultrasonography to investigate embryonic development in two sympatric garter snake species, Thamnophis sirtalis and Thamnophis elegans in the Sierra Nevada mountains of California. This approach allowed us to examine previously hidden reproductive traits including the timing and annual variation in development and differences in parental investment in young. Both species are viviparous, occupy similar ecological niches, and experience the same annual environmental conditions. We found that T. sirtalis embryos were more developmentally advanced than T. elegans embryos during June of three consecutive years. We also found that eggs increased in volume more substantially across developmental stages in T. elegans than in T. sirtalis, indicating differences in maternal provisioning of embryos via placental transfer of water. These findings shed light on interspecific differences in parental investment and timing of development within the same environmental context and demonstrate the value of field ultrasonography for pursuing questions relating to the evolution of reproductive modes, and the ecology of development.}, } @article {pmid29607027, year = {2018}, author = {Best, R and Ruxton, GD and Gardner, A}, title = {Intragroup and intragenomic conflict over chemical defense against predators.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3322-3329}, pmid = {29607027}, issn = {2045-7758}, abstract = {Insects are often chemically defended against predators. There is considerable evidence for a group-beneficial element to their defenses, and an associated potential for individuals to curtail their own investment in costly defense while benefitting from the investments of others, termed "automimicry." Although females in chemically defended taxa often lay their eggs in clusters, leading to siblings living in close proximity, current models of automimicry have neglected kin-selection effects, which may be expected to curb the evolution of such selfishness. Here, we develop a general theory of automimicry that explicitly incorporates kin selection. We investigate how female promiscuity modulates intragroup and intragenomic conflicts overinvestment into chemical defense, finding that individuals are favored to invest less than is optimal for their group, and that maternal-origin genes favor greater investment than do paternal-origin genes. We translate these conflicts into readily testable predictions concerning gene expression patterns and the phenotypic consequences of genomic perturbations, and discuss how our results may inform gene discovery in relation to economically important agricultural products.}, } @article {pmid29607026, year = {2018}, author = {Angers, B and Leung, C and Vétil, R and Deremiens, L and Vergilino, R}, title = {The effects of allospecific mitochondrial genome on the fitness of northern redbelly dace (Chrosomus eos).}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3311-3321}, pmid = {29607026}, issn = {2045-7758}, abstract = {Instantaneous mitochondrial introgression events allow the disentangling of the effects of hybridization from those of allospecific mtDNA. Such process frequently occurred in the fish Chrosomus eos, resulting in cybrid individuals composed of a C. eos nuclear genome but with a C. neogaeus mtDNA. This provides a valuable model to address the fundamental question: How well do introgressed individuals perform in their native environment? We infer where de novo production of cybrids occurred to discriminate native environments from those colonized by cybrids in 25 sites from two regions (West-Qc and East-Qc) in Quebec (Canada). We then compared the relative abundance of wild types and cybrids as a measure integrating both fitness and de novo production of cybrids. According to mtDNA variation, 12 introgression events are required to explain the diversity of cybrids. Five cybrid lineages could not be associated with in situ introgression events. This includes one haplotype carried by 93% of the cybrids expected to have colonized West-Qc. These cybrids also displayed a nearly complete allopatric distribution with wild types. We still inferred de novo production of cybrids at seven sites, that accounted for 70% of the cybrids in East-Qc. Wild-type and cybrid individuals coexist in all East-Qc sites while cybrids were less abundant. Allopatry of cybrids restricted to the postglacial expansion suggests the existence of higher fitness for cybrids in specific conditions, allowing for the colonization of different environments and expanding the species' range. However, allospecific mtDNA does not provide a higher fitness to cybrids in their native environment compared to wild types, making the success of an introgressed lineage uncertain.}, } @article {pmid29607025, year = {2018}, author = {Fialho, VS and Rodrigues, VB and Elliot, SL}, title = {Nesting strategies and disease risk in necrophagous beetles.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3296-3310}, pmid = {29607025}, issn = {2045-7758}, abstract = {While the effects of carcass decomposition on microorganisms have been demonstrated in recent years, little is known of how this impacts necrophagous insects. A common assumption is that insects that exploit carcasses are exposed to a high density of potentially harmful microorganisms, but no field data have so far validated this. Necrophagous beetles such as the Scarabaeinae have complex nesting behaviors with elaborate parental care. So here, we begin to explore whether this conjunction of life history and nesting behavior represents an adaptive response to the threat posed by microbes in these environments, mainly by entomopathogens. We evaluated the density and distribution of fungi and bacteria from soil near the carcasses, and their ability to infect and kill insects that are in contact with this soil during the decomposition process. Our data showed an increase in the density and activity of opportunistic or facultative pathogens during the apex of decomposition, when there is a predominance of necrophagous insects. Meanwhile, the survivorship of bait insects decreased when in contact with soil from this period of decomposition, indicating a potential risk of infection. However, the density and activity of these microorganisms decreased with distance from the carcass, mainly with depth, which would benefit tunneller beetles in particular. We have thus provided the first field data to show that necrophagous insects are indeed exposed to high densities of potentially harmful microorganisms. Furthermore, we propose that some parental care strategies may have arisen not only as a response to competition, but also as adaptations that reduce the risks of disease. Although we have focused on carrion feeders, we suggest that the same occurs with coprophagous beetles, as both carrion and dung are nutrient-rich resources.}, } @article {pmid29607024, year = {2018}, author = {Rossato, DO and Boligon, D and Fornel, R and Kronforst, MR and Gonçalves, GL and Moreira, GRP}, title = {Subtle variation in size and shape of the whole forewing and the red band among co-mimics revealed by geometric morphometric analysis in Heliconius butterflies.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3280-3295}, pmid = {29607024}, issn = {2045-7758}, abstract = {Heliconius are unpalatable butterflies that exhibit remarkable intra- and interspecific variation in wing color pattern, specifically warning coloration. Species that have converged on the same pattern are often clustered in Müllerian mimicry rings. Overall, wing color patterns are nearly identical among co-mimics. However, fine-scale differences exist, indicating that factors in addition to natural selection may underlie wing phenotype. Here, we investigate differences in shape and size of the forewing and the red band in the Heliconius postman mimicry ring (H. erato phyllis and the co-mimics H. besckei, H. melpomene burchelli, and H. melpomene nanna) using a landmark-based approach. If phenotypic evolution is driven entirely by predation pressure, we expect nonsignificant differences among co-mimics in terms of wing shape. Also, a reinforcement of wing pattern (i.e., greater similarity) could occur when co-mimics are in sympatry. We also examined variation in the red forewing band because this trait is critical for both mimicry and sexual communication. Morphometric results revealed significant but small differences among species, particularly in the shape of the forewing of co-mimics. Although we did not observe greater similarity when co-mimics were in sympatry, nearly identical patterns provided evidence of convergence for mimicry. In contrast, mimetic pairs could be distinguished based on the shape (but not the size) of the red band, suggesting an "advergence" process. In addition, sexual dimorphism in the red band shape (but not size) was found for all lineages. Thus, we infer that natural selection due to predation by birds might not be the only mechanism responsible for variation in color patterns, and sexual selection could be an important driver of wing phenotypic evolution in this mimicry ring.}, } @article {pmid29607023, year = {2018}, author = {Ospina, EA and Merrill, L and Benson, TJ}, title = {Incubation temperature impacts nestling growth and survival in an open-cup nesting passerine.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3270-3279}, pmid = {29607023}, issn = {2045-7758}, abstract = {For oviparous species such as birds, conditions experienced while in the egg can have long-lasting effects on the individual. The impact of subtle changes in incubation temperature on nestling development, however, remains poorly understood, especially for open-cup nesting species with altricial young. To investigate how incubation temperature affects nestling development and survival in such species, we artificially incubated American robin (Turdus migratorius) eggs at 36.1°C ("Low" treatment) and 37.8°C ("High" treatment). Chicks were fostered to same-age nests upon hatching, and we measured mass, tarsus, and wing length of experimental nestlings and one randomly selected, naturally incubated ("Natural"), foster nest-mate on days 7 and 10 posthatch. We found significant effects of incubation temperature on incubation duration, growth, and survival, in which experimentally incubated nestlings had shorter incubation periods (10.22, 11.50, and 11.95 days for High, Low, and Natural eggs, respectively), and nestlings from the Low treatment were smaller and had reduced survival compared to High and Natural nestlings. These results highlight the importance of incubation conditions during embryonic development for incubation duration, somatic development, and survival. Moreover, these findings indicate that differences in incubation temperature within the natural range of variation can have important carryover effects on growth and survival in species with altricial young.}, } @article {pmid29607022, year = {2018}, author = {Pan, Y and Zhang, Y and Sun, S}, title = {Habitat orientation alters the outcome of interspecific competition: A microcosm study with zooplankton grazers.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3254-3269}, pmid = {29607022}, issn = {2045-7758}, abstract = {Habitat orientation has recently been demonstrated to affect the foraging behavior, growth, and production of plankton grazers. Because the orientation effect may vary with species, we hypothesize that habitat orientation may alter interspecific interactions between animal species. We experimentally investigated how habitat orientation (placing cuboid chambers in three orientations with long, medium, and small side as the chamber height) affected the interaction between two common cladoceran species, Daphnia magna and Moina micrura, which competitively exploited green algae of Chlorella pyrenoidosa at two volume scales (64 and 512 ml). Results show that chamber orientation and volume additively affected the behavior and species performance of the grazers. Specifically, both grazer species generally decreased their average swimming velocity, grazing rate (on algal cells), body size, and survival and reproduction rates with increasing chamber height for both chamber volumes and with decreasing chamber volume regardless of chamber orientation. Nevertheless, the decrease magnitude was greater for M. micrura with increasing chamber height but was greater for D. magna with decreasing chamber volume. Correspondingly, when cocultured, the density ratio of D. magna to M. micrura increased with increasing chamber height but decreased with decreasing chamber volume. At the end of the experiment, none of D. magna individuals survived in the small and short (large-based) chambers, and few M. micrura individuals survived in large and tall (small-based) chambers. These results indicate that both habitat orientation and size affect the outcome of interspecific competition between grazer species. We suggest that variation in habitat orientation may improve community coexistence and species diversity in nature.}, } @article {pmid29607021, year = {2018}, author = {Suarez-Rubio, M and Ille, C and Bruckner, A}, title = {Insectivorous bats respond to vegetation complexity in urban green spaces.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3240-3253}, pmid = {29607021}, issn = {2045-7758}, abstract = {Structural complexity is known to determine habitat quality for insectivorous bats, but how bats respond to habitat complexity in highly modified areas such as urban green spaces has been little explored. Furthermore, it is uncertain whether a recently developed measure of structural complexity is as effective as field-based surveys when applied to urban environments. We assessed whether image-derived structural complexity (MIG) was as/more effective than field-based descriptors in this environment and evaluated the response of insectivorous bats to structural complexity in urban green spaces. Bat activity and species richness were assessed with ultrasonic devices at 180 locations within green spaces in Vienna, Austria. Vegetation complexity was assessed using 17 field-based descriptors and by calculating the mean information gain (MIG) using digital images. Total bat activity and species richness decreased with increasing structural complexity of canopy cover, suggesting maneuverability and echolocation (sensorial) challenges for bat species using the canopy for flight and foraging. The negative response of functional groups to increased complexity was stronger for open-space foragers than for edge-space foragers. Nyctalus noctula, a species foraging in open space, showed a negative response to structural complexity, whereas Pipistrellus pygmaeus, an edge-space forager, was positively influenced by the number of trees. Our results show that MIG is a useful, time- and cost-effective tool to measure habitat complexity that complemented field-based descriptors. Response of insectivorous bats to structural complexity was group- and species-specific, which highlights the need for manifold management strategies (e.g., increasing or reinstating the extent of ground vegetation cover) to fulfill different species' requirements and to conserve insectivorous bats in urban green spaces.}, } @article {pmid29607020, year = {2018}, author = {Stover, KK and Weinreich, DM and Roberts, TJ and Brainerd, EL}, title = {Patterns of musculoskeletal growth and dimensional changes associated with selection and developmental plasticity in domestic and wild strain turkeys.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3229-3239}, pmid = {29607020}, issn = {2045-7758}, support = {R01 AR055295/AR/NIAMS NIH HHS/United States ; }, abstract = {Domestication is a type of experimental evolution in which humans have artificially selected for specific desired traits. Selected strain animals can be utilized to identify correlated responses by comparing them to the wild strain. In particular, domestic turkeys have been selected for increased body mass and high-growth rate, most significantly over the past 60 years. Yet it remains unclear how artificial selection has affected the morphology and evolution of the musculoskeletal system as a whole. Here, we compare growth rate over 21 weeks, hind limb bone scaling across ontogeny via in vivo CT scanning, and muscle proportions in wild and domestic turkeys to identify differences in structural scaling and the potential contributions of selection and developmental plasticity to whole-organism morphology. The domestic turkeys grew at a higher rate (0.14 kg/day vs. 0.05 kg/day) and reached over 3 times the body mass of wild birds. Comparing the proportional muscle masses in adult turkeys, only the trunk had a greater mass ratio in the domestic turkey, driven solely by M. pectoralis (2.8 times larger). The proportional increase in only breast meat and no other muscles highlights the surgical precision attainable with artificial selection. The domestic turkey femur and tibiotarsus displayed increases in polar moment of area, apparently maintaining torsional strength as body mass increased. The lack of dimensional change in the more vertically held tarsometatarsus is consistent with the pattern expected due to developmental plasticity. These results from the domestic turkey emphasize that there are morphological limits to preserving the balance between growth and function, and varying rates of trait evolution can further complicate this equilibrium.}, } @article {pmid29607019, year = {2018}, author = {Fors, L and Mozuraitis, R and Blažytė-Čereškienė, L and Verschut, TA and Hambäck, PA}, title = {Selection by parasitoid females among closely related hosts based on volatiles: Identifying relevant chemical cues.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3219-3228}, pmid = {29607019}, issn = {2045-7758}, abstract = {Parasitoid fitness is influenced by the ability to overcome host defense strategies and by the ability of parasitoid females to select high-quality host individuals. When females are unable to differentiate among hosts, their fitness will decrease with an increasing abundance of resistant hosts. To understand the effect of mixed host populations on female fitness, it is therefore necessary to investigate the ability of female parasitoids to select among hosts. Here, we used behavioral assays, headspace volatile collection, and electrophysiology to study the ability of Asecodes parviclava to use olfactory cues to select between a susceptible host (Galerucella calmariensis) and a resistant host (Galerucella pusilla) from a distance. Our studies show that parasitoid females have the capacity to distinguish the two hosts and that the selection behavior is acquired through experiences during earlier life stages. Further, we identified two volatiles (α-terpinolene and [E]-β-ocimene) which amounts differ between the two plant-herbivore systems and that caused behavioral and electrophysiological responses. The consequence of this selection behavior is that females have the capacity to avoid laying eggs in G. pusilla, where the egg mortality is higher due to much stronger immune responses toward A. parviclava than in larvae of G. calmariensis.}, } @article {pmid29607018, year = {2018}, author = {Akalusi, ME and Bourque, CP}, title = {Effect of climatic variation on the morphological characteristics of 37-year-old balsam fir provenances planted in a common garden in New Brunswick, Canada.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3208-3218}, pmid = {29607018}, issn = {2045-7758}, abstract = {The extent of the effect of projected changes in climate on trees remains unclear. This study investigated the effect of climatic variation on morphological traits of balsam fir [Abies balsamea (L.) Mill.] provenances sourced from locations spanning latitudes from 44° to 51°N and longitudes from 53° to 102°W across North America, growing in a common garden in eastern Canada. Lower latitude provenances performed significantly better than higher latitude provenances (p < .05) with regard to diameter at breast height (DBH), height (H), and crown width (CW), a distinction indicative of genotypic control of these traits. There was, however, no significant difference among provenances in terms of survival (p > .05), an indication of a resource allocation strategy directed at survival relative to productivity in higher latitude provenances as seen in their lower DBH, H, and CW compared to the lower latitude provenances. Temperature had a stronger relationship with DBH, H, and CW than precipitation, a reflection of adaptation to local conditions in populations of the species along latitudinal gradients. Both climatic variables had some effect on tree survival. These results suggest that the response of balsam fir to climatic variation will likely not be uniform in the species, but differ based on genetic characteristics between populations located in the northern and southern parts of the species' range. Population differences in response to climatic variation may be evident earlier in growth traits, compared to survival in balsam fir. The findings of this study will facilitate modeling in the species that is reflective of genetic variation in response to climatic conditions, and guide provenance selection for utilization in terms of productivity or resilience as well as breeding programs directed at obtaining species that possibly combine both traits.}, } @article {pmid29607017, year = {2018}, author = {Wang, S and Fu, WL and Du, W and Zhang, Q and Li, Y and Lyu, YS and Wang, XF}, title = {Nectary tracks as pollinator manipulators: The pollination ecology of Swertia bimaculata (Gentianaceae).}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3187-3207}, pmid = {29607017}, issn = {2045-7758}, abstract = {Floral nectaries are closely associated with biotic pollination, and the nectar produced by corolla nectaries is generally enclosed in floral structures. Although some Swertia spp. (Gentianaceae), including S. bimaculata, evolved a peculiar form of corolla nectaries (known as "gland patches") arranged in a conspicuous ring on the rotate corolla and that completely expose their nectar, little is known about the pollination of these plants. Two hypotheses were made concerning the possible effects of gland patches: visual attraction and visitor manipulation. The floral traits, mating system, and insect pollination of S. bimaculata were examined, and the pollination effects of gland patches were evaluated. A comparative study was made using Swertia kouitchensis, a species with fimbriate nectaries. Swertia bimaculata flowers were protandrous, with obvious stamen movement leading to herkogamy in the female phase and to a significant reduction in nectary-anther distance. The species is strongly entomophilous and facultatively xenogamous. The daily reward provided per flower decreased significantly after the male phase. The most effective pollinators were large dipterans, and the visiting proportion of Diptera was significantly higher in S. bimaculata than in S. kouitchensis. Most visitors performed "circling behavior" in S. bimaculata flowers. Removing or blocking the nectaries caused no reduction in visiting frequency but a significant reduction in visit duration, interrupting the circling behavior. The circling behavior was encouraged by nectar abundance and promoted pollen dispersal. Visitor species with small body size had little chance to contact the anthers or stigma, revealing a filtration effect exerted by the floral design. These results rejected the "visual attraction" hypothesis and supported the "visitor manipulation" hypothesis. The nectary whorl within a flower acted like a ring-shaped track that urged nectar foragers to circle on the corolla, making pollination in S. bimaculata flowers more orderly and selective than that in classically generalist flowers.}, } @article {pmid29607016, year = {2018}, author = {Johansson, J and Brännström, Å and Metz, JAJ and Dieckmann, U}, title = {Twelve fundamental life histories evolving through allocation-dependent fecundity and survival.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3172-3186}, pmid = {29607016}, issn = {2045-7758}, abstract = {An organism's life history is closely interlinked with its allocation of energy between growth and reproduction at different life stages. Theoretical models have established that diminishing returns from reproductive investment promote strategies with simultaneous investment into growth and reproduction (indeterminate growth) over strategies with distinct phases of growth and reproduction (determinate growth). We extend this traditional, binary classification by showing that allocation-dependent fecundity and mortality rates allow for a large diversity of optimal allocation schedules. By analyzing a model of organisms that allocate energy between growth and reproduction, we find twelve types of optimal allocation schedules, differing qualitatively in how reproductive allocation increases with body mass. These twelve optimal allocation schedules include types with different combinations of continuous and discontinuous increase in reproduction allocation, in which phases of continuous increase can be decelerating or accelerating. We furthermore investigate how this variation influences growth curves and the expected maximum life span and body size. Our study thus reveals new links between eco-physiological constraints and life-history evolution and underscores how allocation-dependent fitness components may underlie biological diversity.}, } @article {pmid29607015, year = {2018}, author = {Bailes, EJ and Pattrick, JG and Glover, BJ}, title = {An analysis of the energetic reward offered by field bean (Vicia faba) flowers: Nectar, pollen, and operative force.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3161-3171}, pmid = {29607015}, issn = {2045-7758}, abstract = {Global consumption of crops with a yield that is dependent on animal pollinators is growing, with greater areas planted each year. However, the floral traits that influence pollinator visitation are not usually the focus of breeding programmes, and therefore, it is likely that yield improvements may be made by optimizing floral traits to enhance pollinator visitation rates. We investigated the variation present in the floral reward of the bee-pollinated crop Vicia faba (field bean). We examined the genetic potential for breeding flowers with a greater reward into current commercial varieties and used bee behavioral experiments to gain insight into the optimal nectar concentration to maximize bee preference. There was a large range of variation in the amount of pollen and nectar reward of flowers in the genotypes investigated. Bee behavioral experiments using nectar sugar concentrations found in V. faba lines suggest that Bombus terrestris prefers 55% w/w sugar solution over 40% w/w, but has no preference between 55% w/w and 68% w/w sugar solution. We provide a first indication of the force required to open V. faba flowers. Our results provide a valuable starting point toward breeding for varieties with optimized floral reward. Field studies are now needed to verify whether the genetic potential for breeding more rewarding flowers can translate into higher yield and yield stability.}, } @article {pmid29607014, year = {2018}, author = {D'Acunto, LE and Pauli, BP and Moy, M and Johnson, K and Abu-Omar, J and Zollner, PA}, title = {Timing and technique impact the effectiveness of road-based, mobile acoustic surveys of bats.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3152-3160}, pmid = {29607014}, issn = {2045-7758}, abstract = {Mobile acoustic surveys are a common method of surveying bat communities. However, there is a paucity of empirical studies exploring different methods for conducting mobile road surveys of bats. During 2013, we conducted acoustic mobile surveys on three routes in north-central Indiana, U.S.A., using (1) a standard road survey, (2) a road survey where the vehicle stopped for 1 min at every half mile of the survey route (called a "start-stop method"), and (3) a road survey with an individual using a bicycle. Linear mixed models with multiple comparison procedures revealed that when all bat passes were analyzed, using a bike to conduct mobile surveys detected significantly more bat passes per unit time compared to other methods. However, incorporating genus-level comparisons revealed no advantage to using a bike over vehicle-based methods. We also found that survey method had a significant effect when analyses were limited to those bat passes that could be identified to genus, with the start-stop method generally detecting more identifiable passes than the standard protocol or bike survey. Additionally, we found that significantly more identifiable bat passes (particularly those of the Eptesicus and Lasiurus genera) were detected in surveys conducted immediately following sunset. As governing agencies, particularly in North America, implement vehicle-based bat monitoring programs, it is important for researchers to understand how variations on protocols influence the inference that can be gained from different monitoring schemes.}, } @article {pmid29607013, year = {2018}, author = {Schultz, AJ and Cristescu, RH and Littleford-Colquhoun, BL and Jaccoud, D and Frère, CH}, title = {Fresh is best: Accurate SNP genotyping from koala scats.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3139-3151}, pmid = {29607013}, issn = {2045-7758}, abstract = {Maintaining genetic diversity is a crucial component in conserving threatened species. For the iconic Australian koala, there is little genetic information on wild populations that is not either skewed by biased sampling methods (e.g., sampling effort skewed toward urban areas) or of limited usefulness due to low numbers of microsatellites used. The ability to genotype DNA extracted from koala scats using next-generation sequencing technology will not only help resolve location sample bias but also improve the accuracy and scope of genetic analyses (e.g., neutral vs. adaptive genetic diversity, inbreeding, and effective population size). Here, we present the successful SNP genotyping (1272 SNP loci) of koala DNA extracted from scat, using a proprietary DArTseq™ protocol. We compare genotype results from two-day-old scat DNA and 14-day-old scat DNA to a blood DNA template, to test accuracy of scat genotyping. We find that DNA from fresher scat results in fewer loci with missing information than DNA from older scat; however, 14-day-old scat can still provide useful genetic information, depending on the research question. We also find that a subset of 209 conserved loci can accurately identify individual koalas, even from older scat samples. In addition, we find that DNA sequences identified from scat samples through the DArTseq™ process can provide genetic identification of koala diet species, bacterial and viral pathogens, and parasitic organisms.}, } @article {pmid29607012, year = {2018}, author = {Hossie, TJ and MacFarlane, S and Clement, A and Murray, DL}, title = {Threat of predation alters aggressive interactions among spotted salamander (Ambystoma maculatum) larvae.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3131-3138}, pmid = {29607012}, issn = {2045-7758}, abstract = {Intraspecific aggression represents a major source of mortality for many animals and is often experienced alongside the threat of predation. The presence of predators can strongly influence ecological systems both directly by consuming prey and indirectly by altering prey behavior or habitat use. As such, the threat of attack by higher level predators may strongly influence agonistic interactions among conspecifics via nonconsumptive (e.g., behaviorally mediated) predator effects. We sought to investigate these interactions experimentally using larval salamanders (Ambystoma maculatum) as prey and dragonfly nymphs (Anax junius) as predators. Specifically, we quantified salamander behavioral responses to perceived predation risk (PPR) from dragonfly nymphs and determined the degree to which PPR influenced intraspecific aggression (i.e., intraspecific biting and cannibalism) among prey. This included examining the effects of predator exposure on the magnitude of intraspecific biting (i.e., extent of tail damage) and the resulting change in performance (i.e., burst swim speed). Salamander larvae responded to PPR by reducing activity and feeding, but did not increase refuge use. Predator exposure did not significantly influence overall survival; however, the pattern of survival differed among treatments. Larvae exposed to PPR experienced less tail damage from conspecifics, and maximum burst swim speed declined as tail damage became more extensive. Thus, escape ability was more strongly compromised by intraspecific aggression occurring in the absence of predation risk. We conclude that multitrophic indirect effects may importantly modulate intraspecific aggression and should be considered when evaluating the effects of intraspecific competition.}, } @article {pmid29607011, year = {2018}, author = {Ramón-Laca, A and White, DJ and Weir, JT and Robertson, HA}, title = {Extraction of DNA from captive-sourced feces and molted feathers provides a novel method for conservation management of New Zealand kiwi (Apteryx spp.).}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3119-3130}, pmid = {29607011}, issn = {2045-7758}, abstract = {Although some taxa are increasing in number due to active management and predator control, the overall number of kiwi (Apteryx spp.) is declining. Kiwi are cryptic and rare, meaning current monitoring tools, such as call counts, radio telemetry, and surveys using detection dogs are labor-intensive, yield small datasets, and require substantial resources or provide inaccurate estimates of population sizes. A noninvasive genetic approach could help the conservation effort. We optimized a panel of 23 genetic markers (22 autosomal microsatellite loci and an allosomal marker) to discriminate between all species of kiwi and major lineages within species, while simultaneously determining sex. Markers successfully amplified from both fecal and shed feather DNA samples collected in captivity. We found that DNA extraction was more efficient from shed feathers, but DNA quality was greater with feces, although this was sampling dependent. Our microsatellite panel was able to distinguish between contemporary kiwi populations and lineages and provided PI values in the range of 4.3 × 10-5 to 2.0 × 10-19, which in some cases were sufficient for individualization and mark-recapture studies. As such, we have tested a wide-reaching, noninvasive molecular approach that will improve conservation management by providing better parameter estimates associated with population ecology and demographics such as abundance, growth rates, and genetic diversity.}, } @article {pmid29607010, year = {2018}, author = {Liu, Z and Baoyin, T and Sun, J and Minggagud, H and Li, X}, title = {Plant sizes mediate mowing-induced changes in nutrient stoichiometry and allocation of a perennial grass in semi-arid grassland.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3109-3118}, pmid = {29607010}, issn = {2045-7758}, abstract = {While mowing-induced changes in plant traits and their effects on ecosystem functioning in semi-arid grassland are well studied, the relations between plant size and nutrient strategies are largely unknown. Mowing may drive the shifts of plant nutrient limitation and allocation. Here, we evaluated the changes in nutrient stoichiometry and allocation with variations in sizes of Leymus chinensis, the dominant plant species in Inner Mongolia grassland, to various mowing frequencies in a 17-yr controlled experiment. Affected by mowing, the concentrations of nitrogen (N), phosphorus (P), and carbon (C) in leaves and stems were significantly increased, negatively correlating with plant sizes. Moreover, we found significant trade-offs between the concentrations and accumulation of N, P, and C in plant tissues. The N:P ratios of L. chinensis aboveground biomass, linearly correlating with plant size, significantly decreased with increased mowing frequencies. The ratios of C:N and C:P of L. chinensis individuals were positively correlated with plant size, showing an exponential pattern. With increased mowing frequencies, L. chinensis size was correlated with the allocation ratios of leaves to stems of N, P, and C by the tendencies of negative parabola, positive, and negative linear. The results of structure equation modeling showed that the N, P, and C allocations were co-regulated by biomass allocation and nutrient concentration ratios of leaves to stems. In summary, we found a significant decoupling effect between plant traits and nutrient strategies along mowing frequencies. Our results reveal a mechanism for how long-term mowing-induced changes in concentrations, accumulations, ecological stoichiometry, and allocations of key elements are mediated by the variations in plant sizes of perennial rhizome grass.}, } @article {pmid29607009, year = {2018}, author = {Chen, S and Cunningham, AA and Wei, G and Yang, J and Liang, Z and Wang, J and Wu, M and Yan, F and Xiao, H and Harrison, XA and Pettorelli, N and Turvey, ST}, title = {Determining threatened species distributions in the face of limited data: Spatial conservation prioritization for the Chinese giant salamander (Andrias davidianus).}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3098-3108}, pmid = {29607009}, issn = {2045-7758}, abstract = {The purpose of this study was to determine whether limited occurrence data for highly threatened species can provide useful spatial information to inform conservation. The study was conducted across central and southern China. We developed a habitat suitability model for the Critically Endangered Chinese giant salamander (Andrias davidianus) based on one biotic and three abiotic parameters from single-site locality records, which represent the only relevant environmental data available for this species. We then validated model quality by testing whether increased percentage of predicted suitable habitat at the county level correlated with independent data on giant salamander presence. We randomly selected 48 counties containing historical records which were distinct from, and independent of, the single-site records used to develop the model, and 47 additional counties containing >50% predicted suitable habitat. We interviewed 2,812 respondents near potential giant salamander habitat across these counties and tested for differences in respondent giant salamander reports between counties selected using each method. Our model predicts that suitable giant salamander habitat is found widely across central and southern China, with counties containing ≥50% predicted suitable habitat distributed in 13 provinces. Counties with historical records contain significantly more predicted suitable habitat than counties without historical records. There are no statistical differences in any patterns of respondent giant salamander reports in surveyed counties selected from our model compared with the areas of known historical giant salamander distribution. A Chinese giant salamander habitat suitability model with strong predictive power can be derived from the restricted range of environmental variables associated with limited available presence-only occurrence records, constituting a cost-effective strategy to guide spatial allocation of conservation planning. Few reported sightings were recent, however, with most being over 20 years old, so that identification of areas of suitable habitat does not necessarily indicate continued survival of the species at these locations.}, } @article {pmid29607008, year = {2018}, author = {van Egmond, EM and van Bodegom, PM and van Hal, JR and van Logtestijn, RSP and Berg, MP and Aerts, R}, title = {Nonadditive effects of consumption in an intertidal macroinvertebrate community are independent of food availability but driven by complementarity effects.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3086-3097}, pmid = {29607008}, issn = {2045-7758}, abstract = {Suboptimal environmental conditions are ubiquitous in nature and commonly drive the outcome of biological interactions in community processes. Despite the importance of biological interactions for community processes, knowledge on how species interactions are affected by a limiting resource, for example, low food availability, remains limited. Here, we tested whether variation in food supply causes nonadditive consumption patterns, using the macroinvertebrate community of intertidal sandy beaches as a model system. We quantified isotopically labeled diatom consumption by three macroinvertebrate species (Bathyporeia pilosa, Haustorius arenarius, and Scolelepis squamata) kept in mesocosms in either monoculture or a three-species community at a range of diatom densities. Our results show that B. pilosa was the most successful competitor in terms of consumption at both high and low diatom density, while H. arenarius and especially S. squamata consumed less in a community than in their respective monocultures. Nonadditive effects on consumption in this macroinvertebrate community were present and larger than mere additive effects, and similar across diatom densities. The underlying species interactions, however, did change with diatom density. Complementarity effects related to niche-partitioning were the main driver of the net diversity effect on consumption, with a slightly increasing contribution of selection effects related to competition with decreasing diatom density. For the first time, we showed that nonadditive effects of consumption are independent of food availability in a macroinvertebrate community. This suggests that, in communities with functionally different, and thus complementary, species, nonadditive effects can arise even when food availability is low. Hence, at a range of environmental conditions, species interactions hold important potential to alter ecosystem functioning.}, } @article {pmid29607007, year = {2018}, author = {St-Pierre, AP and Shikon, V and Schneider, DC}, title = {Count data in biology-Data transformation or model reformation?.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3077-3085}, pmid = {29607007}, issn = {2045-7758}, abstract = {Statistical analyses are an integral component of scientific research, and for decades, biologists have applied transformations to data to meet the normal error assumptions for F and t tests. Over the years, there has been a movement from data transformation toward model reformation-the use of non-normal error structures within the framework of the generalized linear model (GLM). The principal advantage of model reformation is that parameters are estimated on the original, rather than the transformed scale. However, data transformation has been shown to give better control over type I error, for simulated data with known error structures. We conducted a literature review of statistical textbooks directed toward biologists and of journal articles published in the primary literature to determine temporal trends in both the text recommendations and the practice in the refereed literature over the past 35 years. In this review, a trend of increasing use of reformation in the primary literature was evident, moving from no use of reformation before 1996 to >50% of the articles reviewed applying GLM after 2006. However, no such trend was observed in the recommendations in statistical textbooks. We then undertook 12 analyses based on published datasets in which we compared the type I error estimates, residual plot diagnostics, and coefficients yielded by analyses using square root transformations, log transformations, and the GLM. All analyses yielded acceptable residual versus fit plots and had similar p-values within each analysis, but as expected, the coefficient estimates differed substantially. Furthermore, no consensus could be found in the literature regarding a procedure to back-transform the coefficient estimates obtained from linear models performed on transformed datasets. This lack of consistency among coefficient estimates constitutes a major argument for model reformation over data transformation in biology.}, } @article {pmid29607006, year = {2018}, author = {Del Valle, JC and Gallardo-López, A and Buide, ML and Whittall, JB and Narbona, E}, title = {Digital photography provides a fast, reliable, and noninvasive method to estimate anthocyanin pigment concentration in reproductive and vegetative plant tissues.}, journal = {Ecology and evolution}, volume = {8}, number = {6}, pages = {3064-3076}, pmid = {29607006}, issn = {2045-7758}, abstract = {Anthocyanin pigments have become a model trait for evolutionary ecology as they often provide adaptive benefits for plants. Anthocyanins have been traditionally quantified biochemically or more recently using spectral reflectance. However, both methods require destructive sampling and can be labor intensive and challenging with small samples. Recent advances in digital photography and image processing make it the method of choice for measuring color in the wild. Here, we use digital images as a quick, noninvasive method to estimate relative anthocyanin concentrations in species exhibiting color variation. Using a consumer-level digital camera and a free image processing toolbox, we extracted RGB values from digital images to generate color indices. We tested petals, stems, pedicels, and calyces of six species, which contain different types of anthocyanin pigments and exhibit different pigmentation patterns. Color indices were assessed by their correlation to biochemically determined anthocyanin concentrations. For comparison, we also calculated color indices from spectral reflectance and tested the correlation with anthocyanin concentration. Indices perform differently depending on the nature of the color variation. For both digital images and spectral reflectance, the most accurate estimates of anthocyanin concentration emerge from anthocyanin content-chroma ratio, anthocyanin content-chroma basic, and strength of green indices. Color indices derived from both digital images and spectral reflectance strongly correlate with biochemically determined anthocyanin concentration; however, the estimates from digital images performed better than spectral reflectance in terms of r2 and normalized root-mean-square error. This was particularly noticeable in a species with striped petals, but in the case of striped calyces, both methods showed a comparable relationship with anthocyanin concentration. Using digital images brings new opportunities to accurately quantify the anthocyanin concentrations in both floral and vegetative tissues. This method is efficient, completely noninvasive, applicable to both uniform and patterned color, and works with samples of any size.}, } @article {pmid29606783, year = {2018}, author = {Williams, DM and Ebach, MC}, title = {A Cladist is a systematist who seeks a natural classification: some comments on Quinn (2017).}, journal = {Biology & philosophy}, volume = {33}, number = {1}, pages = {10}, doi = {10.1007/s10539-018-9621-7}, pmid = {29606783}, issn = {0169-3867}, abstract = {In response to Quinn (Biol Philos, 2017. 10.1007/s10539-017-9577-z) we identify cladistics to be about natural classifications and their discovery and thereby propose to add an eighth cladistic definition to Quinn's list, namely the systematist who seeks to discover natural classifications, regardless of their affiliation, theoretical or methodological justifications.}, } @article {pmid29606782, year = {2018}, author = {Thomas, J and Kirby, S}, title = {Self domestication and the evolution of language.}, journal = {Biology & philosophy}, volume = {33}, number = {1}, pages = {9}, pmid = {29606782}, issn = {0169-3867}, abstract = {We set out an account of how self-domestication plays a crucial role in the evolution of language. In doing so, we focus on the growing body of work that treats language structure as emerging from the process of cultural transmission. We argue that a full recognition of the importance of cultural transmission fundamentally changes the kind of questions we should be asking regarding the biological basis of language structure. If we think of language structure as reflecting an accumulated set of changes in our genome, then we might ask something like, "What are the genetic bases of language structure and why were they selected?" However, if cultural evolution can account for language structure, then this question no longer applies. Instead, we face the task of accounting for the origin of the traits that enabled that process of structure-creating cultural evolution to get started in the first place. In light of work on cultural evolution, then, the new question for biological evolution becomes, "How did those precursor traits evolve?" We identify two key precursor traits: (1) the transmission of the communication system through learning; and (2) the ability to infer the communicative intent associated with a signal or action. We then describe two comparative case studies-the Bengalese finch and the domestic dog-in which parallel traits can be seen emerging following domestication. Finally, we turn to the role of domestication in human evolution. We argue that the cultural evolution of language structure has its origin in an earlier process of self-domestication.}, } @article {pmid29606284, year = {2018}, author = {van Ruiten, MS and Rowland, BD}, title = {SMC Complexes: Universal DNA Looping Machines with Distinct Regulators.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {6}, pages = {477-487}, doi = {10.1016/j.tig.2018.03.003}, pmid = {29606284}, issn = {0168-9525}, abstract = {What drives the formation of chromatin loops has been a long-standing question in chromosome biology. Recent work provides major insight into the basic principles behind loop formation. Structural maintenance of chromosomes (SMC) complexes, that are conserved from bacteria to humans, are key to this process. The SMC family includes condensin and cohesin, which structure chromosomes to enable mitosis and long-range gene regulation. We discuss novel insights into the mechanism of loop formation and the implications for how these complexes ultimately shape chromosomes. A picture is emerging in which these complexes form small loops that they then processively enlarge. It appears that SMC complexes act by family-wide basic principles, with complex-specific levels of control.}, } @article {pmid29606283, year = {2018}, author = {Ng, BG and Freeze, HH}, title = {Perspectives on Glycosylation and Its Congenital Disorders.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {6}, pages = {466-476}, pmid = {29606283}, issn = {0168-9525}, support = {R01 DK099551/DK/NIDDK NIH HHS/United States ; }, abstract = {Congenital disorders of glycosylation (CDG) are a rapidly expanding group of metabolic disorders that result from abnormal protein or lipid glycosylation. They are often difficult to clinically diagnose because they broadly affect many organs and functions and lack clinical uniformity. However, recent technological advances in next-generation sequencing have revealed a treasure trove of new genetic disorders, expanded the knowledge of known disorders, and showed a critical role in infectious diseases. More comprehensive genetic tools specifically tailored for mammalian cell-based models have revealed a critical role for glycosylation in pathogen-host interactions, while also identifying new CDG susceptibility genes. We highlight recent advancements that have resulted in a better understanding of human glycosylation disorders, perspectives for potential future therapies, and mysteries for which we continue to seek new insights and solutions.}, } @article {pmid29606205, year = {2018}, author = {Pickering, TR and Heaton, JL and Clarke, RJ and Stratford, D}, title = {Hominin hand bone fossils from Sterkfontein Caves, South Africa (1998-2003 excavations).}, journal = {Journal of human evolution}, volume = {118}, number = {}, pages = {89-102}, doi = {10.1016/j.jhevol.2018.02.014}, pmid = {29606205}, issn = {1095-8606}, abstract = {We describe eleven hominin metacarpals and phalanges recovered from Jacovec Cavern and Member 4 of the Sterkfontein Formation between 1998 and 2003. Collectively, the fossils date in excess of 2.0 Ma, and are probably attributable to Australopithecus africanus and/or Australopithecus prometheus. When combined with results of previous studies on Australopithecus postcranial functional morphology, the new data presented here suggest that at least some late Pliocene and/or early Pleistocene hominins from Sterkfontein were arboreally adept. This finding accords with the reconstruction of the site's >2.0 Ma catchment area as well-vegetated and containing significant woody components. In addition, most of the new specimens described here evince morphologies that indicate the hands from which they derived lacked complete modern humanlike manual dexterity, which is integral to the manufacture and use of intentionally shaped stone tools. The absence of lithic artifacts from both stratigraphic units from which the fossils were excavated is consistent with this conclusion.}, } @article {pmid29606204, year = {2018}, author = {Rodríguez, J and Mateos, A}, title = {Carrying capacity, carnivoran richness and hominin survival in Europe.}, journal = {Journal of human evolution}, volume = {118}, number = {}, pages = {72-88}, doi = {10.1016/j.jhevol.2018.01.004}, pmid = {29606204}, issn = {1095-8606}, abstract = {Carrying capacity, the maximum biomass that an ecosystem can sustain over the long term, strongly influences several ecological processes and it is also one of the main determinants of biodiversity. Here, we estimate the carrying capacity (CC) of the late Early and early Middle Pleistocene ecosystems of Europe, using equations describing the relationship between CC and climatic variables observed in the present, as well as maps of inferred paleotemperature and paleoprecipitation. Maps of paleoclimate values were interpolated from the composite benthic stable oxygen isotope ratios and a transfer function was used to estimate ungulate carrying capacity (CCU) from the interpolated mean annual temperature and annual precipitation values. Carnivoran carrying capacity was subsequently estimated from ungulate carrying capacity and the effect of CC on the carnivoran faunas was analyzed in 12 paleocommunities from Southern Europe. Our results show that carnivoran species richness is strongly related to ungulate carrying capacity in recent ecosystems, but the late Early Pleistocene paleocommunities from Southern Europe included much richer carnivore guilds than would be expected for a recent community with a similar ungulate carrying capacity. Thus, those late Early Pleistocene ecosystems supported a high number of carnivoran species, but the carnivoran biomass they could support was relatively low. Consequently, carnivorans occurred at low densities in Southern Europe compared to the recent African savanna ecosystems, but likely also compared to coeval East African ecosystems. Consequently, the first Homo populations that arrived in Europe at the end of the late Early Pleistocene found mammal communities consisting of a low number of prey species, which accounted for a moderate herbivore biomass, as well as a diverse but not very abundant carnivore guild. This relatively low carnivoran density implies that the hominin-carnivore encounter rate was lower in the European ecosystems than in the coeval East African environments, suggesting that an opportunistic omnivorous hominin would have benefited from a reduced interference from the carnivore guild.}, } @article {pmid29606203, year = {2018}, author = {Godinho, RM and Fitton, LC and Toro-Ibacache, V and Stringer, CB and Lacruz, RS and Bromage, TG and O'Higgins, P}, title = {The biting performance of Homo sapiens and Homo heidelbergensis.}, journal = {Journal of human evolution}, volume = {118}, number = {}, pages = {56-71}, doi = {10.1016/j.jhevol.2018.02.010}, pmid = {29606203}, issn = {1095-8606}, abstract = {Modern humans have smaller faces relative to Middle and Late Pleistocene members of the genus Homo. While facial reduction and differences in shape have been shown to increase biting efficiency in Homo sapiens relative to these hominins, facial size reduction has also been said to decrease our ability to resist masticatory loads. This study compares crania of Homo heidelbergensis and H. sapiens with respect to mechanical advantages of masticatory muscles, force production efficiency, strains experienced by the cranium and modes of deformation during simulated biting. Analyses utilize X-ray computed tomography (CT) scan-based 3D models of a recent modern human and two H. heidelbergensis. While having muscles of similar cross-sectional area to H. heidelbergensis, our results confirm that the modern human masticatory system is more efficient at converting muscle forces into bite forces. Thus, it can produce higher bite forces than Broken Hill for equal muscle input forces. This difference is the result of alterations in relative in and out-lever arm lengths associated with well-known differences in midfacial prognathism. Apparently at odds with this increased efficiency is the finding that the modern human cranium deforms more, resulting in greater strain magnitudes than Broken Hill when biting at the equivalent tooth. Hence, the facial reduction that characterizes modern humans may not have evolved as a result of selection for force production efficiency. These findings provide further evidence for a degree of uncoupling between form and function in the masticatory system of modern humans. This may reflect the impact of food preparation technologies. These data also support previous suggestions that differences in bite force production efficiency can be considered a spandrel, primarily driven by the midfacial reduction in H. sapiens that occurred for other reasons. Midfacial reduction plausibly resulted in a number of other significant changes in morphology, such as the development of a chin, which has itself been the subject of debate as to whether or not it represents a mechanical adaptation or a spandrel.}, } @article {pmid29606202, year = {2018}, author = {Neaux, D and Sansalone, G and Ledogar, JA and Heins Ledogar, S and Luk, THY and Wroe, S}, title = {Basicranium and face: Assessing the impact of morphological integration on primate evolution.}, journal = {Journal of human evolution}, volume = {118}, number = {}, pages = {43-55}, doi = {10.1016/j.jhevol.2018.02.007}, pmid = {29606202}, issn = {1095-8606}, abstract = {The basicranium and facial skeleton are two integrated structures displaying great morphological diversity across primates. Previous studies focusing on limited taxonomic samples have demonstrated that morphological integration has a significant impact on the evolution of these structures. However, this influence is still poorly understood. A more complete understanding of craniofacial integration across primates has important implications for functional hypotheses of primate evolution. In the present study, we analyzed a large sample of primate species to assess how integration affects the relationship between basicranial and facial evolutionary pathways across the order. First, we quantified integration and modularity between basicranium and face using phylogenetically-informed partial least squares analyses. Then, we defined the influence of morphological integration between these structures on rates of evolution, using a time-calibrated phylogenetic tree, and on disparity through time, comparing the morphological disparity across the tree with that expected under a pure Brownian process. Finally, we assessed the correlation between the basicranium and face, and three factors purported to have an important role in shaping these structures during evolution: endocranial volume, positional behavior (i.e., locomotion and posture), and diet. Our findings show that the face and basicranium, despite being highly integrated, display significantly different evolutionary rates. However, our results demonstrate that morphological integration impacted shape disparity through time. We also found that endocranial volume and positional behavior are important drivers of cranial shape evolution, partly affected by morphological integration.}, } @article {pmid29606201, year = {2018}, author = {Laird, MF and Kozma, EE and Kwekason, A and Harrison, T}, title = {A new fossil cercopithecid tibia from Laetoli and its implications for positional behavior and paleoecology.}, journal = {Journal of human evolution}, volume = {118}, number = {}, pages = {27-42}, doi = {10.1016/j.jhevol.2018.02.005}, pmid = {29606201}, issn = {1095-8606}, abstract = {Detailed analyses and comparisons of postcranial specimens of Plio-Pleistocene cercopithecids provide an opportunity to examine the recent evolutionary history and locomotor diversity in Old World monkeys. Studies examining the positional behavior and substrate preferences of fossil cercopithecids are also important for reconstructing the paleoenvironments of Plio-Pleistocene hominin sites. Here we describe a new fossil cercopithecid tibia (EP 1100/12) from the Australopithecus afarensis-bearing Upper Laetolil Beds (∼3.7 Ma) of Laetoli in northern Tanzania. The fossil tibia is attributed to cf. Rhinocolobus sp., which is the most common colobine at Laetoli. In addition to qualitative comparisons, the tibial shape of EP 1100/12 was compared to that of 190 extant cercopithecids using three-dimensional landmarks. Discriminant function analyses of the shape data were used to assess taxonomic affinity and shape variation relating to positional behavior. EP 1100/12 clustered with extant colobines, particularly the large-bodied genera Nasalis and Rhinopithecus. Comparisons reveal that EP 1100/12 belongs to a large-bodied monkey that engaged in arboreal pronograde quadrupedalism. These findings add further support to previous inferences that woodland and forest environments dominated the paleoenvironment of the Upper Laetolil Beds, which supported the diverse community of cercopithecids at Laetoli. The inferred paleoecology and the presence of large-bodied arboreally-adapted monkeys at Laetoli show that A. afarensis had access to a range of diverse habitats, including woodlands and forests. This supports the possibility that A. afarensis, with its potential range of positional capabilities, was able to utilize arboreal settings for food acquisition and refuge from predators.}, } @article {pmid29606200, year = {2018}, author = {Berthaume, MA and Delezene, LK and Kupczik, K}, title = {Dental topography and the diet of Homo naledi.}, journal = {Journal of human evolution}, volume = {118}, number = {}, pages = {14-26}, doi = {10.1016/j.jhevol.2018.02.006}, pmid = {29606200}, issn = {1095-8606}, abstract = {Though late Middle Pleistocene in age, Homo naledi is characterized by a mosaic of Australopithecus-like (e.g., curved fingers, small brains) and Homo-like (e.g., elongated lower limbs) traits, which may suggest it occupied a unique ecological niche. Ecological reconstructions inform on niche occupation, and are particularly successful when using dental material. Tooth shape (via dental topography) and size were quantified for four groups of South African Plio-Pleistocene hominins (specimens of Australopithecus africanus, Paranthropus robustus, H. naledi, and Homo sp.) on relatively unworn M2s to investigate possible ecological differentiation in H. naledi relative to taxa with similar known geographical ranges. H. naledi has smaller, but higher-crowned and more wear resistant teeth than Australopithecus and Paranthropus. These results are found in both lightly and moderately worn teeth. There are no differences in tooth sharpness or complexity. Combined with the high level of dental chipping in H. naledi, this suggests that, relative to Australopithecus and Paranthropus, H. naledi consumed foods with similar fracture mechanics properties but more abrasive particles (e.g., dust, grit), which could be due to a dietary and/or environmental shift(s). The same factors that differentiate H. naledi from Australopithecus and Paranthropus may also differentiate it from Homo sp., which geologically predates it, in the same way. Compared to the great apes, all hominins have sharper teeth, indicating they consumed foods requiring higher shear forces during mastication. Despite some anatomical similarities, H. naledi likely occupied a distinct ecological niche from the South African hominins that predate it.}, } @article {pmid29606199, year = {2018}, author = {Isbell, LA and Bidner, LR and Van Cleave, EK and Matsumoto-Oda, A and Crofoot, MC}, title = {GPS-identified vulnerabilities of savannah-woodland primates to leopard predation and their implications for early hominins.}, journal = {Journal of human evolution}, volume = {118}, number = {}, pages = {1-13}, doi = {10.1016/j.jhevol.2018.02.003}, pmid = {29606199}, issn = {1095-8606}, abstract = {Predation is thought to have been a key selection pressure in primate evolution, especially in the savannah-woodland habitats where several early hominin species lived. However, predator-primate prey relationships are still poorly understood because human presence often deters predators, limiting our ability to quantify the impact of predation. Synchronized high-resolution tracking of leopards (Panthera pardus), vervets (Chlorocebus pygerythrus), and olive baboons (Papio anubis) during a 14-month study in Kenya revealed that increased vulnerability to leopard predation was not associated with higher encounter rates, smaller body size, smaller group size, or greater distance from refuges, contrary to long-standing inferences. Instead, the initiation, rate, timing, and duration of encounters, outcome of approaches, and predation events showed only a diel pattern of differential vulnerability. In the absence of human observers, vervets were more vulnerable during the day, whereas baboons were more vulnerable at night, but overall neither species was more vulnerable than the other. As our results show that leopards avoided baboons during the day and hunted them at night, we suggest that the same pattern would have applied to hominins-because they were even larger than baboons and bipedal, resulting in similarly offensive capability on the ground during the day but poorer agility in the trees at night, especially as they became committed bipeds. Drawing from hominid behavior and archaeopaleontological and ethnographic evidence, we hypothesize that ground-sleeping hominins initially dealt with this formidable threat by using stone tools to modify Acacia branches into 'bomas', thorny enclosures that provided nighttime shelter. The ability of hominins to create their own nightly refuges on the ground wherever Acacia spp. were available would have allowed them to range more widely, a crucial step in furthering the spread of hominins across Africa and beyond.}, } @article {pmid29606139, year = {2018}, author = {Zhang, B and Ye, H and Yang, A}, title = {Mathematical modelling of interacting mechanisms for hypoxia mediated cell cycle commitment for mesenchymal stromal cells.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {35}, pmid = {29606139}, issn = {1752-0509}, abstract = {BACKGROUND: Existing experimental data have shown hypoxia to be an important factor affecting the proliferation of mesenchymal stromal cells (MSCs), but the contrasting observations made at various hypoxic levels raise the questions of whether hypoxia accelerates proliferation, and how. On the other hand, in order to meet the increasing demand of MSCs, an optimised bioreactor control strategy is needed to enhance in vitro production.

RESULTS: A comprehensive, single-cell mathematical model has been constructed in this work, which combines cellular oxygen sensing with hypoxia-mediated cell cycle progression to predict cell cycle commitment as a proxy to proliferation rate. With oxygen levels defined for in vitro cell culture, the model predicts enhanced proliferation under intermediate (2-8%) and mild (8-15%) hypoxia and cell quiescence under severe (< 2%) hypoxia. Global sensitivity analysis and quasi-Monte Carlo simulation revealed that within a certain range (+/- 100%), model parameters affect (with varying significance) the minimum commitment time, but the existence of a range of optimal oxygen tension could be preserved with the hypothesized effects of Hif2α and reactive oxygen species (ROS). It appears that Hif2α counteracts Hif1α and ROS-mediated protein deactivation under intermediate hypoxia and normoxia (20%), respectively, to regulate the response of cell cycle commitment to oxygen tension.

CONCLUSION: Overall, this modelling study offered an integrative framework to capture several interacting mechanisms and allowed in silico analysis of their individual and collective roles in shaping the hypoxia-mediated commitment to cell cycle. The model offers a starting point to the establishment of a suitable mechanism that can satisfactorily explain the different existing experimental observations from different studies, and warrants future extension and dedicated experimental validation to eventually support bioreactor optimisation.}, } @article {pmid29606137, year = {2018}, author = {Steffens, D and Solomon, M and Vuong, K and Alchin, L and Roberts, R and Koh, C and Young, J}, title = {Effect of timing on baseline quality of life scores among surgical cancer patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {210}, pmid = {29606137}, issn = {1756-0500}, mesh = {Aged ; Female ; Health Status ; Humans ; Male ; Middle Aged ; Neoplasms/*surgery ; Patients/*psychology ; Postoperative Period ; Preoperative Period ; Quality of Life/*psychology ; *Surveys and Questionnaires ; }, abstract = {OBJECTIVES: To investigate differences between quality of life (QoL) scores obtained preoperatively or recalled in the early postoperative period amongst patients undergoing major cancer surgery.

RESULTS: Of the 283 patients included, 133 completed their baseline QoL questionnaire preoperatively and 150 postoperatively. Patient groups were broadly comparable in terms of age however the preoperative group had a lower proportion of patients from non-English speaking backgrounds. There were important and statistically significant differences between mean scores for physical health (overall physical health, physical functioning and role physical domains) and mental health (overall mental health and mental health domains) between pre- and postoperative groups. There were no differences for other domain-specific scores (bodily pain, general health, vitality, social functioning and role emotional).}, } @article {pmid29606122, year = {2018}, author = {Parsons, MH and Kannan, PM}, title = {War zone refugia? Establishing a baseline for protected waterbirds in a wildlife refuge flanked by agriculture and militarization.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {212}, pmid = {29606122}, issn = {1756-0500}, mesh = {Agriculture/methods/trends ; Animals ; Birds/classification/*physiology ; Conservation of Natural Resources/methods ; Endangered Species ; Geography ; Humans ; India ; Pakistan ; Population Dynamics ; *Refugium ; Seasons ; *Warfare ; *Wetlands ; }, abstract = {OBJECTIVES: The welfare of threatened fauna should not be assumed merely because their refuges have been designated with protected status. This is particularly true in geographical areas where social/military events drive an under-reported, but potentially lethal, type of human-wildlife interaction. Waterbirds of Gharana Wetland Conservation Reserve consist mostly of threatened species. However, as occurs globally, 'protected' fauna near contested borders are sometimes affected by military forces. As part of a larger project to document regional avifauna, we report the seasonal status of waterbirds in order to help establish a baseline for comparing conservation of wildlife within contested areas to that of fauna in more secure refuges. We examined 24 avifauna surveys for relationships between seasons, temperature, individuals and species.

RESULTS: 28 of 61 waterbird species were rare. We found seasonal variations in individuals (F3,731 = 3.82; P < 0.01) and species (F3,11 = 5.81; P < 0.05) with a major influx in late winter, rather than autumn. Thus, while this sanctuary serves as an over-wintering site, it is also a stop-over site for high-altitude migrations. While providing this baseline, we offer a reminder that the welfare of wildlife in protected areas should be monitored seasonally, with the ongoing threats to their conservation, carefully documented.}, } @article {pmid29606121, year = {2018}, author = {Shakhtshneider, EV and Mikhailova, SV and Ivanoshchuk, DE and Orlov, PS and Ovsyannikova, AK and Rymar, OD and Ragino, YI and Voevoda, MI}, title = {Polymorphism of the GLIS3 gene in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {211}, pmid = {29606121}, issn = {1756-0500}, support = {14-15-00496-P//Russian Science Foundation/ ; }, mesh = {Aged ; *Carbohydrate Metabolism ; Diabetes Mellitus, Type 2/ethnology/*genetics/metabolism ; European Continental Ancestry Group/genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/ethnology/genetics ; Genotype ; Humans ; Male ; Middle Aged ; *Polymorphism, Single Nucleotide ; Russia ; Transcription Factors/*genetics ; }, abstract = {OBJECTIVE: Earlier, GLIS3 gene polymorphisms have been shown to be associated with the development of maturity onset diabetes of the young (MODY). We screened GLIS3 gene sequences among patients with MODY to identify probably pathogenic variants by whole-exome sequencing. We estimated frequency of rare single-nucleotide variants in the coding region of GLIS3 in a Caucasian population and among individuals with carbohydrate metabolism disorders in Russia.

RESULTS: We identified 15 single-nucleotide variants in GLIS3. Three rare variants (minor allele frequency < 1%) rs806052, rs143051164, and rs149840771 were genotyped in 126 cases of MODY, in 188 patients with type 2 diabetes mellitus (DM2), and 564 randomly selected Caucasian individuals in Russia. A heterozygous rs806052 variant was identified in one patient with DM2; c.1270T frequency was 0.003. Prevalence of rs143051164 c.844G was 0.003 in the control population and 0.004 and 0.003 in MODY and DM2 samples, respectively. Prevalence of rs149840771 c.2096A was 0.003 and 0.004 in the control population and among MODY patients, respectively. In DM2 patients, rs149840771 c.2096A was not identified. We did not detect any associations of rs806052, rs143051164, and rs149840771 with carbohydrate metabolism disorders among patients with MODY and DM2 in Russia.}, } @article {pmid29606099, year = {2018}, author = {Qiu, H and Rossoni, AW and Weber, APM and Yoon, HS and Bhattacharya, D}, title = {Unexpected conservation of the RNA splicing apparatus in the highly streamlined genome of Galdieria sulphuraria.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {41}, pmid = {29606099}, issn = {1471-2148}, support = {PJT200620//Ministry of Oceans and Fisheries of Korea/International ; EF1416785//National Science Foundation/International ; }, mesh = {Amino Acid Sequence ; Conserved Sequence/*genetics ; Eukaryota/genetics ; Evolution, Molecular ; *Genome ; Introns/genetics ; RNA Splicing/*genetics ; RNA, Messenger/genetics/metabolism ; Rhodophyta/*genetics ; Spliceosomes/metabolism ; }, abstract = {BACKGROUND: Genome reduction in intracellular pathogens and endosymbionts is usually compensated by reliance on the host for energy and nutrients. Free-living taxa with reduced genomes must however evolve strategies for generating functional diversity to support their independent lifestyles. An emerging model for the latter case is the Rhodophyta (red algae) that comprises an ecologically widely distributed, species-rich phylum. Red algae have undergone multiple phases of significant genome reduction, including extremophilic unicellular taxa with limited nuclear gene inventories that must cope with hot, highly acidic environments.

RESULTS: Using genomic data from eight red algal lineages, we identified 155 spliceosomal machinery (SM)-associated genes that were putatively present in the red algal common ancestor. This core SM gene set is most highly conserved in Galdieria species (150 SM genes) and underwent differing levels of gene loss in other examined red algae (53-145 SM genes). Surprisingly, the high SM conservation in Galdieria sulphuraria coincides with the enrichment of spliceosomal introns in this species (2 introns/gene) in comparison to other red algae (< 0.34 introns/gene). Spliceosomal introns in G. sulphuraria undergo alternatively splicing, including many that are differentially spliced upon changes in culture temperature.

CONCLUSIONS: Our work reveals the unique nature of G. sulphuraria among red algae with respect to the conservation of the spliceosomal machinery and introns. We discuss the possible implications of these findings in the highly streamlined genome of this free-living eukaryote.}, } @article {pmid29606093, year = {2018}, author = {Palumbo, D and Affinito, O and Monticelli, A and Cocozza, S}, title = {DNA Methylation variability among individuals is related to CpGs cluster density and evolutionary signatures.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {229}, pmid = {29606093}, issn = {1471-2164}, support = {PROJECT SP6.6//CNR EPIGEN FLAGSHIP/ ; }, mesh = {*CpG Islands ; *DNA Methylation ; Epigenesis, Genetic ; Evolution, Molecular ; Genetic Code ; *Genetic Variation ; Healthy Volunteers ; Humans ; Male ; Selection, Genetic ; }, abstract = {BACKGROUND: In recent years, epigenetics has gained a central role in the understanding of the process of natural selection. It is now clear how environmental impacts on the methylome could promote methylation variability with direct effects on disease etiology as well as phenotypic and genotypic variations in evolutionary processes. To identify possible factors influencing inter-individual methylation variability, we studied methylation values standard deviation of 166 healthy individuals searching for possible associations with genomic features and evolutionary signatures.

RESULTS: We analyzed methylation variability values in relation to CpG cluster density and we found a strong association between them (p-value < 2.2 × 10- 16). Furthermore, we found that genes related to CpGs with high methylation variability values were enriched for immunological pathways; instead, those associated with low ones were enriched for pathways related to basic cellular functions. Finally, we found an association between methylation variability values and signals of both ancient (p-value < 2.2 × 10- 16) and recent selective pressure (p-value < 1 × 10- 4).

CONCLUSION: Our results indicate the presence of an intricate interplay between genetics, epigenetic code and evolutionary constraints in humans.}, } @article {pmid29606092, year = {2018}, author = {Naguleswaran, A and Doiron, N and Roditi, I}, title = {RNA-Seq analysis validates the use of culture-derived Trypanosoma brucei and provides new markers for mammalian and insect life-cycle stages.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {227}, pmid = {29606092}, issn = {1471-2164}, support = {31003A_166427//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 55007650//Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genetic Markers ; Life Cycle Stages ; Protozoan Proteins/*genetics ; Sequence Analysis, RNA/*methods ; Trypanosoma brucei brucei/genetics/*growth & development ; Tsetse Flies/*parasitology ; }, abstract = {BACKGROUND: Trypanosoma brucei brucei, the parasite causing Nagana in domestic animals, is closely related to the parasites causing sleeping sickness, but does not infect humans. In addition to its importance as a pathogen, the relative ease of genetic manipulation and an innate capacity for RNAi extend its use as a model organism in cell and infection biology. During its development in its mammalian and insect (tsetse fly) hosts, T. b. brucei passes through several different life-cycle stages. There are currently four life-cycle stages that can be cultured: slender forms and stumpy forms, which are equivalent to forms found in the mammal, and early and late procyclic forms, which are equivalent to forms in the tsetse midgut. Early procyclic forms show coordinated group movement (social motility) on semi-solid surfaces, whereas late procyclic forms do not.

RESULTS: RNA-Seq was performed on biological replicates of each life-cycle stage. These constitute the first datasets for culture-derived slender and stumpy bloodstream forms and early and late procyclic forms. Expression profiles confirmed that genes known to be stage-regulated in the animal and insect hosts were also regulated in culture. Sequence reads of 100-125 bases provided sufficient precision to uncover differential expression of closely related genes. More than 100 transcripts showed peak expression in stumpy forms, including adenylate cyclases and several components of inositol metabolism. Early and late procyclic forms showed differential expression of 73 transcripts, a number of which encoded proteins that were previously shown to be stage-regulated. Moreover, two adenylate cyclases previously shown to reduce social motility are up-regulated in late procyclic forms.

CONCLUSIONS: This study validates the use of cultured bloodstream forms as alternatives to animal-derived parasites and yields new markers for all four stages. In addition to underpinning recent findings that early and late procyclic forms are distinct life-cycle stages, it could provide insights into the reasons for their different biological properties.}, } @article {pmid29606089, year = {2018}, author = {Chen, S and Chen, J and Hou, F and Feng, Y and Zhang, R}, title = {iTRAQ-based quantitative proteomic analysis reveals the lateral meristem developmental mechanism for branched spike development in tetraploid wheat (Triticum turgidum L.).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {228}, pmid = {29606089}, issn = {1471-2164}, mesh = {Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Gene Ontology ; Gene Regulatory Networks ; Meristem/genetics/growth & development/metabolism ; Molecular Sequence Annotation ; Plant Proteins/genetics/*metabolism ; Proteomics/*methods ; *Tetraploidy ; Triticum/genetics/*growth & development/metabolism ; }, abstract = {BACKGROUND: Spike architecture mutants in tetraploid wheat (Triticum turgidum L., 2n = 28, AABB) have a distinct morphology, with parts of the rachis node producing lateral meristems that develop into ramified spikelete (RSs) or four-rowed spikelete (FRSs). The genetic basis of RSs and FRSs has been analyzed, but little is known about the underlying developmental mechanisms of the lateral meristem. We used isobaric tags for relative and absolute quantitation (iTRAQ) to perform a quantitative proteomic analysis of immature spikes harvested from tetraploid near-isogenic lines of wheat with normal spikelete (NSs), FRSs, and RSs and investigated the molecular mechanisms of lateral meristem differentiation and development. This work provides valuable insight into the underlying functions of the lateral meristem and how it can produce differences in the branching of tetraploid wheat spikes.

RESULTS: Using an iTRAQ-based shotgun quantitation approach, 104 differential abundance proteins (DAPs) with < 1% false discovery rate (FDR) and a 1.5-fold change (> 1.50 or < 0.67) were identified by comparing FRS with NS and RS with NS genotypes. To determine the functions of the proteins, 38 co-expressed DAPs from the two groups were annotated using the Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analytical tools. We discovered that proteins involved in "post-embryonic development" and "metabolic pathways" such as carbohydrate and nitrogen metabolism could be used to construct a developmentally associated network. Additionally, 6 out of 38 DAPs in the network were analyzed using quantitative real-time polymerase chain reaction, and the correlation coefficient between proteomics and qRT-PCR was 0.7005. These key genes and proteins were closely scrutinized and discussed.

CONCLUSIONS: Here, we predicted that DAPs involved in "post-embryonic development" and "metabolic pathways" may be responsible for the spikelete architecture changes in FRS and RS. Furthermore, we discussed the potential function of several vital DAPs from GO and KEGG analyses that were closely related to histone modification, ubiquitin-mediated protein degradation, transcription factors, carbohydrate and nitrogen metabolism and heat shock proteins (HSPs). This work provides valuable insight into the underlying functions of the lateral meristem in the branching of tetraploid wheat spikes.}, } @article {pmid29605546, year = {2018}, author = {Lukeš, J and Butenko, A and Hashimi, H and Maslov, DA and Votýpka, J and Yurchenko, V}, title = {Trypanosomatids Are Much More than Just Trypanosomes: Clues from the Expanded Family Tree.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {466-480}, doi = {10.1016/j.pt.2018.03.002}, pmid = {29605546}, issn = {1471-5007}, mesh = {Animals ; Biodiversity ; *Biological Evolution ; Host-Parasite Interactions ; Humans ; Insecta/*parasitology ; Trypanosomatina/*classification/genetics/physiology ; }, abstract = {Trypanosomes and leishmanias are widely known parasites of humans. However, they are just two out of several phylogenetic lineages that constitute the family Trypanosomatidae. Although dixeny - the ability to infect two hosts - is a derived trait of vertebrate-infecting parasites, the majority of trypanosomatids are monoxenous. Like their common ancestor, the monoxenous Trypanosomatidae are mostly parasites or commensals of insects. This review covers recent advances in the study of insect trypanosomatids, highlighting their diversity as well as genetic, morphological and biochemical complexity, which, until recently, was underappreciated. The investigation of insect trypanosomatids is providing an important foundation for understanding the origin and evolution of parasitism, including colonization of vertebrates and the appearance of human pathogens.}, } @article {pmid29605155, year = {2018}, author = {Nguyen, HP and Van Broeckhoven, C and van der Zee, J}, title = {ALS Genes in the Genomic Era and their Implications for FTD.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {6}, pages = {404-423}, doi = {10.1016/j.tig.2018.03.001}, pmid = {29605155}, issn = {0168-9525}, abstract = {Amyotrophic lateral sclerosis (ALS) is a complex neurodegenerative disease, characterized genetically by a disproportionately large contribution of rare genetic variation. Driven by advances in massive parallel sequencing and applied on large patient-control cohorts, systematic identification of these rare variants that make up the genetic architecture of ALS became feasible. In this review paper, we present a comprehensive overview of recently proposed ALS genes that were identified based on rare genetic variants (TBK1, CHCHD10, TUBA4A, CCNF, MATR3, NEK1, C21orf2, ANXA11, TIA1) and their potential relevance to frontotemporal dementia genetic etiology. As more causal and risk genes are identified, it has become apparent that affected individuals can carry multiple disease-associated variants. In light of this observation, we discuss the oligogenic architecture of ALS. To end, we highlight emerging key molecular processes and opportunities for therapy.}, } @article {pmid29605087, year = {2018}, author = {Heethoff, M}, title = {Cryptic Species - Conceptual or Terminological Chaos? A Response to Struck et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {310}, doi = {10.1016/j.tree.2018.02.006}, pmid = {29605087}, issn = {1872-8383}, } @article {pmid29605086, year = {2018}, author = {Yang, J and Cao, M and Swenson, NG}, title = {Why Functional Traits Do Not Predict Tree Demographic Rates.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {326-336}, doi = {10.1016/j.tree.2018.03.003}, pmid = {29605086}, issn = {1872-8383}, mesh = {Demography ; *Forests ; *Phenotype ; Population Dynamics ; Trees/*physiology ; }, abstract = {Foundational to trait-based community ecology is the expectation that functional traits determine demographic outcomes. However, trait-demographic rate relationships are frequently weak, particularly in tree communities. The foundation of trait-based tree community ecology may, therefore, appear to be unstable. Here we argue that there are three core reasons why trait-demographic relationships are generally weak in tree communities. Specifically, important contextual information is frequently ignored, there is too much focus on species relative to individuals, and there are dimensions of tree function that are critical for determining tree demographic rates that are not captured by easily measured functional traits. Rather than being evidence that trait-based community ecology is fundamentally flawed, these issues elucidate a pathway towards a more robust research program.}, } @article {pmid29605085, year = {2018}, author = {Pearson, DE and Ortega, YK and Eren, Ö and Hierro, JL}, title = {Community Assembly Theory as a Framework for Biological Invasions.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {313-325}, doi = {10.1016/j.tree.2018.03.002}, pmid = {29605085}, issn = {1872-8383}, mesh = {*Biological Evolution ; *Ecosystem ; *Introduced Species ; Models, Biological ; }, abstract = {Biological invasions present a global problem underlain by an ecological paradox that thwarts explanation: how do some exotic species, evolutionarily naïve to their new environments, outperform locally adapted natives? We propose that community assembly theory provides a framework for addressing this question. Local community assembly rules can be defined by evaluating how native species' traits interact with community filters to affect species abundance. Evaluation of exotic species against this benchmark indicates that exotics that follow assembly rules behave like natives, while those exhibiting novel interactions with community filters can greatly underperform or outperform natives. Additionally, advantages gained by exotics over natives following disturbance can be explained by accounting for extrinsic assembly processes that bias exotic traits toward ruderal strategies.}, } @article {pmid29604249, year = {2018}, author = {Williams, JS and Hsu, JY and Rossi, CC and Artinger, KB}, title = {Requirement of zebrafish pcdh10a and pcdh10b in melanocyte precursor migration.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29604249}, issn = {1095-564X}, support = {F31 DE024953/DE/NIDCR NIH HHS/United States ; P30 NS048154/NS/NINDS NIH HHS/United States ; R01 DE017699/DE/NIDCR NIH HHS/United States ; }, abstract = {Melanocytes derive from neural crest cells, which are a highly migratory population of cells that play an important role in pigmentation of the skin and epidermal appendages. In most vertebrates, melanocyte precursor cells migrate solely along the dorsolateral pathway to populate the skin. However, zebrafish melanocyte precursors also migrate along the ventromedial pathway, in route to the yolk, where they interact with other neural crest derivative populations. Here, we demonstrate the requirement for zebrafish paralogs pcdh10a and pcdh10b in zebrafish melanocyte precursor migration. pcdh10a and pcdh10b are expressed in a subset of melanocyte precursor and somatic cells respectively, and knockdown and TALEN mediated gene disruption of pcdh10a results in aberrant migration of melanocyte precursors resulting in fully melanized melanocytes that differentiate precociously in the ventromedial pathway. Live cell imaging analysis demonstrates that loss of pchd10a results in a reduction of directed cell migration of melanocyte precursors, caused by both increased adhesion and a loss of cell-cell contact with other migratory neural crest cells. Also, we determined that the paralog pcdh10b is upregulated and can compensate for the genetic loss of pcdh10a. Disruption of pcdh10b alone by CRISPR mutagenesis results in somite defects, while the loss of both paralogs results in enhanced migratory melanocyte precursor phenotype and embryonic lethality. These results reveal a novel role for pcdh10a and pcdh10b in zebrafish melanocyte precursor migration and suggest that pcdh10 paralogs potentially interact for proper transient migration along the ventromedial pathway.}, } @article {pmid29604055, year = {2018}, author = {Barrera-Redondo, J and Ramírez-Barahona, S and Eguiarte, LE}, title = {Rates of molecular evolution in tree ferns are associated with body size, environmental temperature, and biological productivity.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1050-1062}, doi = {10.1111/evo.13475}, pmid = {29604055}, issn = {1558-5646}, abstract = {Variation in rates of molecular evolution (heterotachy) is a common phenomenon among plants. Although multiple theoretical models have been proposed, fundamental questions remain regarding the combined effects of ecological and morphological traits on rate heterogeneity. Here, we used tree ferns to explore the correlation between rates of molecular evolution in chloroplast DNA sequences and several morphological and environmental factors within a Bayesian framework. We revealed direct and indirect effects of body size, biological productivity, and temperature on substitution rates, where smaller tree ferns living in warmer and less productive environments tend to have faster rates of molecular evolution. In addition, we found that variation in the ratio of nonsynonymous to synonymous substitution rates (dN/dS) in the chloroplast rbcL gene was significantly correlated with ecological and morphological variables. Heterotachy in tree ferns may be influenced by effective population size associated with variation in body size and productivity. Macroevolutionary hypotheses should go beyond explaining heterotachy in terms of mutation rates and instead, should integrate population-level factors to better understand the processes affecting the tempo of evolution at the molecular level.}, } @article {pmid29604047, year = {2018}, author = {Fialko, K}, title = {Digest: Context matters: The effects of light environment and female presence on the structure of wolf spider courtship displays.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1189-1190}, doi = {10.1111/evo.13471}, pmid = {29604047}, issn = {1558-5646}, abstract = {Does variation in the environment in which a signal is presented affect the components of a complex, ritualized animal display? Using a signal phenotype network, Rosenthal et al. (2018) found that light and female presence alter the structure of wolf spider courtship displays, providing evidence that complex signaling behaviors may be modified depending on the social and environmental context.}, } @article {pmid29604041, year = {2018}, author = {Culumber, ZW and Kraft, B and Lemakos, V and Hoffner, E and Travis, J and Hughes, KA}, title = {GxG epistasis in growth and condition and the maintenance of genetic polymorphism in Gambusia holbrooki.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1146-1154}, doi = {10.1111/evo.13474}, pmid = {29604041}, issn = {1558-5646}, abstract = {Theory on indirect genetic effects (IGEs) indicates that variation in the genetic composition of social groups can generate GxG epistasis that may promote the evolution of stable polymorphisms. Using a livebearing fish with a genetic polymorphism in coloration and associated behavioral differences, we tested whether genotypes of social partners interacted with focal individual genotypes to influence growth and condition over 16 weeks of development. We found that IGEs had a significant influence on patterns of feeding, regardless of focal fish genotype. There was no influence of social environment on juvenile length, but there was significant GxG epistasis for body condition. Each focal juvenile was in better condition when its own genotype was not present in adult social partners. These data are consistent with negative frequency-dependent selection in which each morph performs better when it is rare. Neither variation in feeding nor activity-related behaviors explained variation in body condition, suggesting that GxG epistasis for condition was caused by physiological differences between the two genotypes. These findings indicate that GxG epistasis in a given polymorphism can generate fitness landscapes that contribute to the maintenance of that polymorphism and to maintenance of genetic variation for additional fitness-related traits.}, } @article {pmid29603731, year = {2018}, author = {Ferris, KG and Willis, JH}, title = {Differential adaptation to a harsh granite outcrop habitat between sympatric Mimulus species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {6}, pages = {1225-1241}, doi = {10.1111/evo.13476}, pmid = {29603731}, issn = {1558-5646}, support = {S10 OD018164/OD/NIH HHS/United States ; }, abstract = {Understanding which environmental variables and traits underlie adaptation to harsh environments is difficult because many traits evolve simultaneously as populations or species diverge. Here, we investigate the ecological variables and traits that underlie Mimulus laciniatus' adaptation to granite outcrops compared to its sympatric, mesic-adapted progenitor, Mimulus guttatus. We use fine-scale measurements of soil moisture and herbivory to examine differences in selective forces between the species' habitats, and measure selection on flowering time, flower size, plant height, and leaf shape in a reciprocal transplant using M. laciniatus × M. guttatus F4 hybrids. We find that differences in drought and herbivory drive survival differences between habitats, that M. laciniatus and M. guttatus are each better adapted to their native habitat, and differential habitat selection on flowering time, plant stature, and leaf shape. Although early flowering time, small stature, and lobed leaf shape underlie plant fitness in M. laciniatus' seasonally dry environment, increased plant size is advantageous in a competitive mesic environment replete with herbivores like M. guttatus'. Given that we observed divergent selection between habitats in the direction of species differences, we conclude that adaptation to different microhabitats is an important component of reproductive isolation in this sympatric species pair.}, } @article {pmid29603725, year = {2018}, author = {Spagopoulou, F and Blom, MPK}, title = {Digest: Life history evolution in Darwin's dream ponds.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1186-1188}, doi = {10.1111/evo.13473}, pmid = {29603725}, issn = {1558-5646}, abstract = {Can variation in sex-specific parental investment lead to sexual dimorphism in immune response? Keller et al. (2018) measured immune cell parameters, expression of candidate genes, and composition of buccal microbiota in mouthbrooding cichlid species from Lake Tanganyika that show either maternal or biparental care. They found that maternal mouthbrooding species have increased sexual dimorphism in immune parameters, while biparental mouthbrooders exhibit an upregulated adaptive immune response, suggesting resource allocation shifts between parental investment and the immune system.}, } @article {pmid29603716, year = {2018}, author = {Hawkins, NJ}, title = {Digest: Plants adapt under attack: genotypic selection and phenotypic plasticity under herbivore pressure.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1184-1185}, doi = {10.1111/evo.13472}, pmid = {29603716}, issn = {1558-5646}, abstract = {Plant species adapt to changing environmental conditions through phenotypic plasticity and natural selection. Agrawal et al. (2018) found that dandelions responded to the presence of insect pests by producing higher levels of defensive compounds. This defensive response resulted both from phenotypic plasticity, with individual plants' defenses triggered by insect attack, and from evolution by natural selection acting on genetic variation in the plant population.}, } @article {pmid29603471, year = {2018}, author = {Sottas, C and Reif, J and Kuczyński, L and Reifová, R}, title = {Interspecific competition promotes habitat and morphological divergence in a secondary contact zone between two hybridizing songbirds.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {914-923}, doi = {10.1111/jeb.13275}, pmid = {29603471}, issn = {1420-9101}, abstract = {Interspecific competition is assumed to play an important role in the ecological differentiation of species and speciation. However, empirical evidence for competition's role in speciation remains surprisingly scarce. Here, we studied the role of interspecific competition in the ecological differentiation and speciation of two closely related songbird species, the Common Nightingale (Luscinia megarhynchos) and the Thrush Nightingale (Luscinia luscinia). Both species are insectivorous and ecologically very similar. They hybridize in a secondary contact zone, which is a mosaic of sites where both species co-occur (syntopy) and sites where only one species is present (allotopy). We analysed fine-scale habitat data for both species in both syntopic and allotopic sites and looked for associations between habitat use and bill morphology, which have been previously shown to be more divergent in sympatry than in allopatry. We found that the two nightingale species differ in habitat use in allotopic sites, where L. megarhynchos occurred in drier habitats and at slightly higher elevations, but not in syntopic sites. Birds from allotopic sites also showed higher interspecific divergence in relative bill size compared to birds from syntopic sites. Finally, we found an association between bill morphology and elevation. Our results are consistent with the view that interspecific competition in nightingales has resulted in partial habitat segregation in sympatry and that the habitat-specific food supply has in turn very likely led to bill size divergence. Such ecological divergence may enhance prezygotic as well as extrinsic postzygotic isolation and thus accelerate the completion of the speciation process.}, } @article {pmid29603189, year = {2018}, author = {Christie, K and Strauss, SY}, title = {Along the speciation continuum: Quantifying intrinsic and extrinsic isolating barriers across five million years of evolutionary divergence in California jewelflowers.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1063-1079}, doi = {10.1111/evo.13477}, pmid = {29603189}, issn = {1558-5646}, abstract = {Understanding the relative roles of intrinsic and extrinsic reproductive barriers, and their interplay within the geographic context of diverging taxa, remains an outstanding challenge in the study of speciation. We conducted a comparative analysis of reproductive isolation in California Jewelflowers (Streptanthus, s.l., Brassicaceae) by quantifying potential barriers to gene flow at multiple life history stages in 39 species pairs spanning five million years of evolutionary divergence. We quantified nine potential pre- and postzygotic barriers and explored patterns of reproductive isolation in relation to genetic distance. Intrinsic postzygotic isolation was initially weak, increased at intermediate genetic distances, and reached a threshold characterized by complete genetic incompatibility. Climatic niche differences were strong at shallow genetic distances, and species pairs with overlapping ranges showed slight but appreciable phenological isolation, highlighting the potential for ecological barriers to contribute to speciation. Geographic analyses suggest that speciation is not regionally allopatric in the California Jewelflowers, as recently diverged taxa occur in relatively close proximity and display substantial range overlap. Young pairs are characterized by incomplete intrinsic postzygotic isolation, suggesting that extrinsic barriers or fine-scale spatial segregation are more important early in the divergence process than genetic incompatibilities.}, } @article {pmid29602807, year = {2018}, author = {Edwards, M and Cai, H and Abubaker-Sharif, B and Long, Y and Lampert, TJ and Devreotes, PN}, title = {Insight from the maximal activation of the signal transduction excitable network in Dictyostelium discoideum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3722-E3730}, pmid = {29602807}, issn = {1091-6490}, support = {R35 GM118177/GM/NIGMS NIH HHS/United States ; T32 GM007309/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/physiology/ultrastructure ; Cell Adhesion ; Cell Movement ; Cell Shape ; Chemotaxis ; Dictyostelium/genetics/*physiology/ultrastructure ; Enzyme Activation ; Microscopy, Fluorescence ; Microscopy, Phase-Contrast ; Mutation, Missense ; PTEN Phosphohydrolase/genetics/physiology ; Phenotype ; Protozoan Proteins/genetics/*physiology ; Recombinant Proteins/metabolism ; Signal Transduction/*physiology ; rap1 GTP-Binding Proteins/genetics/physiology ; }, abstract = {Cell migration requires the coordination of an excitable signal transduction network involving Ras and PI3K pathways with cytoskeletal activity. We show that expressing activated Ras GTPase-family proteins in cells lacking PTEN or other mutations which increase cellular protrusiveness transforms cells into a persistently activated state. Leading- and trailing-edge markers were found exclusively at the cell perimeter and the cytosol, respectively, of the dramatically flattened cells. In addition, the lifetimes of dynamic actin puncta were increased where they overlapped with actin waves, suggesting a mechanism for the coupling between these two networks. All of these phenotypes could be reversed by inhibiting signal transduction. Strikingly, maintaining cells in this state of constant activation led to a form of cell death by catastrophic fragmentation. These findings provide insight into the feedback loops that control excitability of the signal transduction network, which drives migration.}, } @article {pmid29602806, year = {2018}, author = {Smirnova, I and Kasho, V and Jiang, X and Chen, HM and Withers, SG and Kaback, HR}, title = {Oversized galactosides as a probe for conformational dynamics in LacY.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4146-4151}, pmid = {29602806}, issn = {1091-6490}, support = {R01 GM120043/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Biological Transport, Active ; Crystallography, X-Ray ; Escherichia coli Proteins/chemistry/*metabolism ; Fluorescent Dyes ; Galactose/chemistry/metabolism ; Galactosides/chemistry/*metabolism ; Kinetics ; Ligands ; Models, Molecular ; Molecular Structure ; Monosaccharide Transport Proteins/chemistry/*metabolism ; Periplasm/metabolism ; Protein Binding ; Protein Conformation ; Structure-Activity Relationship ; Symporters/chemistry/*metabolism ; }, abstract = {Binding kinetics of α-galactopyranoside homologs with fluorescent aglycones of different sizes and shapes were determined with the lactose permease (LacY) of Escherichia coli by FRET from Trp151 in the binding site of LacY to the fluorophores. Fast binding was observed with LacY stabilized in an outward-open conformation (kon = 4-20 μM-1·s-1), indicating unobstructed access to the binding site even for ligands that are much larger than lactose. Dissociation rate constants (koff) increase with the size of the aglycone so that Kd values also increase but remain in the micromolar range for each homolog. Phe27 (helix I) forms an apparent constriction in the pathway for sugar by protruding into the periplasmic cavity. However, replacement of Phe27 with a bulkier Trp does not create an obstacle in the pathway even for large ligands, since binding kinetics remain unchanged. High accessibility of the binding site is also observed in a LacY/nanobody complex with partially blocked periplasmic opening. Remarkably, E. coli expressing WT LacY catalyzes transport of α- or β-galactopyranosides with oversized aglycones such as bodipy or Aldol518, which may require an extra space within the occluded intermediate. The results confirm that LacY specificity is strictly directed toward the galactopyranoside ring and also clearly indicate that the opening on the periplasmic side is sufficiently wide to accommodate the large galactoside derivatives tested here. We conclude that the actual pathway for the substrate entering from the periplasmic side is wider than the pore diameter calculated in the periplasmic-open X-ray structures.}, } @article {pmid29602619, year = {2018}, author = {Taylor, LF and Yuan, Y}, title = {Structure of Herpesvirus Capsid Sheds Light on Drug Discovery.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {391-392}, doi = {10.1016/j.tim.2018.03.003}, pmid = {29602619}, issn = {1878-4380}, mesh = {*Capsid ; Capsid Proteins ; Drug Discovery ; *Herpesvirus 8, Human ; Mutagenesis ; }, abstract = {The atomic resolution structure of Kaposi's sarcoma-associated herpesvirus (KSHV) capsid reveals that protein-protein interfaces (PPIs) are essential for its structural stability. This structural information guided a mutagenesis study that identified novel drug targets interrupting PPIs essential for capsid assembly.}, } @article {pmid29602541, year = {2018}, author = {Stewart, KM and Rufolo, SJ}, title = {Kanapoi revisited: Paleoecological and biogeographical inferences from the fossil fish.}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2018.01.008}, pmid = {29602541}, issn = {1095-8606}, abstract = {Fish fossils were recovered from three different depositional contexts at the Pliocene Kanapoi site to: 1) test the assumption that habitat and ecology of modern fish taxa can predict habitat and ecology of fossil taxa; 2) reconstruct the lake and river environments in the Kanapoi Formation, with reference to fish fossils from the nearby Lothagam site deposits; and 3) investigate biogeographical inferences from the fossils. We compare the Kanapoi fish taxa and their depositional environments with the taxa and environments in modern Lake Turkana, and with another Plio-Pleistocene fauna from the eastern Turkana Basin. Taphonomic caveats are discussed. Our results support the use of ecological preferences of modern fish to predict past preferences. Our analysis of the Kanapoi fossils also indicates that the Pliocene Lonyumun Lake had a diverse fauna, with an unusual mix of taxa compared to the modern lake. The presence of possibly endemic species in the Pliocene lake may additionally represent a period of isolation during this epoch. Few fish fossils were recovered in the deposits of the ancestral Kerio River, a primary affluent of Lonyumun Lake then as now, but those present indicate a different ecology than that interpreted for the modern lake. Previously unknown fish taxa which enter the lake during the Pliocene suggest the existence of a connection between the Nile River and the Turkana Basin, which may have been viable for other vertebrates, including hominins.}, } @article {pmid29602213, year = {2018}, author = {Martínez-Juárez, A and López-Luna, MA and Porras-Gómez, TJ and Moreno-Mendoza, N}, title = {Expression of the Sox9, Foxl2, Vasa, and TRPV4 genes in the ovaries and testes of the Morelet's crocodile, Crocodylus moreletii.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {3}, pages = {148-164}, doi = {10.1002/jez.b.22799}, pmid = {29602213}, issn = {1552-5015}, mesh = {3-Hydroxysteroid Dehydrogenases/genetics/metabolism ; Animals ; DEAD-box RNA Helicases/genetics/*metabolism ; Female ; Gene Expression Regulation/*physiology ; Male ; Ovary/*metabolism ; SOX9 Transcription Factor/genetics/*metabolism ; TRPV Cation Channels/genetics/*metabolism ; Testis/*metabolism ; }, abstract = {The Sox9 gene is important for determining sex in vertebrates, as well as for maintaining testis morphology and fertility during adult life. In the same way, Vasa is an important gene for the maintenance of the germinal lineage and has been highly conserved throughout evolution, as it is expressed in germ cells of both vertebrates and invertebrates. In the particular case of crocodiles, the expression of Sox9 during gonadal morphogenesis and in the testes of 3-month-old Alligator mississippiensis has been studied. However, it is interesting to carry out studies on other species of crocodiles in relation to their particular mechanism for sex determination influenced by temperature. In this work, we investigated the expression of the Sox9, Vasa, Foxl2, and TRPV4 genes in the ovaries and testes of 5-year-old juvenile crocodiles from Crocodylus moreletii. As expected, Sox9 expression was found in males, but surprisingly, it was also found in females. For the first time, the expression of Vasa was reported in spermatogonia, oogonia, and oocytes of 5-year-old crocodiles. Foxl2 is important for the development and maintenance of the ovary during adult life in vertebrates; moreover, Foxl2 protein and transcripts are both highly expressed in the ovaries compared to the testes. A possible upstream regulator of the Sox9 gene in reptiles has not yet been discovered; as such, the expression of the TRPV4 ion channel was evaluated. The TRPV4 ion channel was expressed in the cytoplasm of Sertoli and follicular cells and was therefore proposed as a possible regulator of SOX9.}, } @article {pmid29602205, year = {2018}, author = {Bickelmann, C and Frota-Lima, GN and Triepel, SK and Kawaguchi, A and Schneider, I and Fröbisch, NB}, title = {Noncanonical Hox, Etv4, and Gli3 gene activities give insight into unique limb patterning in salamanders.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {3}, pages = {138-147}, doi = {10.1002/jez.b.22798}, pmid = {29602205}, issn = {1552-5015}, mesh = {Animals ; Body Patterning/*genetics ; Cloning, Molecular ; Extremities/*growth & development ; Gene Expression Regulation, Developmental/physiology ; Genes, Homeobox/*physiology ; Larva/growth & development ; Phylogeny ; Proto-Oncogene Proteins/*physiology ; Urodela/*growth & development ; Zinc Finger Protein Gli3/genetics/*physiology ; }, abstract = {Limb development in salamanders is unique among tetrapods in significant ways. Not only can salamanders regenerate lost limbs repeatedly and throughout their lives, but also the preaxial zeugopodial element and digits form before the postaxial ones and, hence, with a reversed polarity compared to all other tetrapods. Moreover, in salamanders with free-swimming larval stages, as exemplified by the axolotl (Ambystoma mexicanum), each digit buds independently, instead of undergoing a paddle stage. Here, we report gene expression patterns of Hoxa and d clusters, and other crucial transcription factors during axolotl limb development. During early phases of limb development, expression patterns are mostly similar to those reported for amniotes and frogs. Likewise, Hoxd and Shh regulatory landscapes are largely conserved. However, during late digit-budding phases, remarkable differences are present: (i) the Hoxd13 expression domain excludes developing digits I and IV, (ii) we expand upon previous observation that Hoxa11 expression, which traditionally marks the zeugopodium, extends distally into the developing digits, and (iii) Gli3 and Etv4 show prolonged expression in developing digits. Our findings identify derived patterns in the expression of key transcription factors during late phases of salamander limb development, and provide the basis for a better understanding of the unique patterning of salamander limbs.}, } @article {pmid29600411, year = {2018}, author = {Sabu, R and Aswani, R and Prabhakaran, P and Krishnakumar, B and Radhakrishnan, EK}, title = {Differential Modulation of Endophytic Microbiome of Ginger in the Presence of Beneficial Organisms, Pathogens and Both as Identified by DGGE Analysis.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1033-1037}, pmid = {29600411}, issn = {1432-0991}, support = {010 - 40/FSHP/2010CSTE//The Kerala State Council for Science, Technology and Environment for the KSCSTE - Fellowship/ ; 274/2015, KSCSTE Dated 6 July 2015//Kerala State Council for Science, Technology and Environment -Science Research Scheme/ ; }, mesh = {Burkholderia/classification/*metabolism ; Denaturing Gradient Gel Electrophoresis ; Disease Resistance/*physiology ; Endophytes/classification/*growth & development ; Ginger/*microbiology ; Microbiota/physiology ; Plant Diseases/microbiology/*prevention & control ; Pythium/growth & development ; RNA, Ribosomal, 16S/genetics ; Rhizome/microbiology ; }, abstract = {Endophytic microorganisms play a significant role in plants response to beneficial organisms and pathogens. In the current study, endophytic microorganisms from Zingiber officinale were screened for in vitro inhibition against Pythium myriotylum. From this, Burkholderia vietnamiensis ZoB74 was selected as an organism with remarkable antifungal effect. Further, the study focussed on analysis of in vivo changes in endophytic bacterial community of Z. officinale in presence of selected organisms and the pathogen P. myriotylum by PCR-DGGE. 16S rDNA sequencing of bacterial community after DGGE has resulted in the identification of a group of uncultured bacteria as the predominant microbial community of rhizome under various conditions of treatment. High frequency dominance of these endophytic bacteria suggests their role in disease resistance to soft rot in ginger. This also revealed the variation of endophytic microbiome of Z. officinale under biotic stress. Hence the study provides molecular insight into uncultured microbiome and its stress-inducible variation in ginger rhizome.}, } @article {pmid29599549, year = {2018}, author = {Bakolis, I and Hammoud, R and Smythe, M and Gibbons, J and Davidson, N and Tognin, S and Mechelli, A}, title = {Urban Mind: Using Smartphone Technologies to Investigate the Impact of Nature on Mental Well-Being in Real Time.}, journal = {Bioscience}, volume = {68}, number = {2}, pages = {134-145}, pmid = {29599549}, issn = {0006-3568}, abstract = {Existing evidence on the beneficial effects of nature on mental health comes from studies using cross-sectional designs. We developed a smartphone-based tool (Urban Mind; www.urbanmind.info) to examine how exposure to natural features within the built environment affects mental well-being in real time. The tool was used to monitor 108 individuals who completed 3013 assessments over a 1-week period. Significant immediate and lagged associations with mental well-being were found for several natural features. These associations were stronger in people with higher trait impulsivity, a psychological measure of one's tendency to behave with little forethought or consideration of the consequences, which is indicative of a higher risk of developing mental-health issues. Our investigation suggests that the benefits of nature on mental well-being are time-lasting and interact with an individual's vulnerability to mental illness. These findings have potential implications from the perspectives of global mental health as well as urban planning and design.}, } @article {pmid29599548, year = {2018}, author = {Ellwood, ER and Kimberly, P and Guralnick, R and Flemons, P and Love, K and Ellis, S and Allen, JM and Best, JH and Carter, R and Chagnoux, S and Costello, R and Denslow, MW and Dunckel, BA and Ferriter, MM and Gilbert, EE and Goforth, C and Groom, Q and Krimmel, ER and LaFrance, R and Martinec, JL and Miller, AN and Minnaert-Grote, J and Nash, T and Oboyski, P and Paul, DL and Pearson, KD and Pentcheff, ND and Roberts, MA and Seltzer, CE and Soltis, PS and Stephens, R and Sweeney, PW and von Konrat, M and Wall, A and Wetzer, R and Zimmerman, C and Mast, AR}, title = {Worldwide Engagement for Digitizing Biocollections (WeDigBio): The Biocollections Community's Citizen-Science Space on the Calendar.}, journal = {Bioscience}, volume = {68}, number = {2}, pages = {112-124}, pmid = {29599548}, issn = {0006-3568}, abstract = {The digitization of biocollections is a critical task with direct implications for the global community who use the data for research and education. Recent innovations to involve citizen scientists in digitization increase awareness of the value of biodiversity specimens; advance science, technology, engineering, and math literacy; and build sustainability for digitization. In support of these activities, we launched the first global citizen-science event focused on the digitization of biodiversity specimens: Worldwide Engagement for Digitizing Biocollections (WeDigBio). During the inaugural 2015 event, 21 sites hosted events where citizen scientists transcribed specimen labels via online platforms (DigiVol, Les Herbonautes, Notes from Nature, the Smithsonian Institution's Transcription Center, and Symbiota). Many citizen scientists also contributed off-site. In total, thousands of citizen scientists around the world completed over 50,000 transcription tasks. Here, we present the process of organizing an international citizen-science event, an analysis of the event's effectiveness, and future directions-content now foundational to the growing WeDigBio event.}, } @article {pmid29599547, year = {2018}, author = {Baldwin, RF and Trombulak, SC and Leonard, PB and Noss, RF and Hilty, JA and Possingham, HP and Scarlett, L and Anderson, MG}, title = {The Future of Landscape Conservation.}, journal = {Bioscience}, volume = {68}, number = {2}, pages = {60-63}, pmid = {29599547}, issn = {0006-3568}, } @article {pmid29599546, year = {2018}, author = {Overbeck, GE and Bergallo, HG and Grelle, CEV and Akama, A and Bravo, F and Colli, GR and Magnusson, WE and Tomas, WM and Fernandes, GW}, title = {Global Biodiversity Threatened by Science Budget Cuts in Brazil.}, journal = {Bioscience}, volume = {68}, number = {1}, pages = {11-12}, pmid = {29599546}, issn = {0006-3568}, } @article {pmid29599501, year = {2018}, author = {Sedlazeck, FJ and Lee, H and Darby, CA and Schatz, MC}, title = {Piercing the dark matter: bioinformatics of long-range sequencing and mapping.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {329-346}, doi = {10.1038/s41576-018-0003-4}, pmid = {29599501}, issn = {1471-0064}, abstract = {Several new genomics technologies have become available that offer long-read sequencing or long-range mapping with higher throughput and higher resolution analysis than ever before. These long-range technologies are rapidly advancing the field with improved reference genomes, more comprehensive variant identification and more complete views of transcriptomes and epigenomes. However, they also require new bioinformatics approaches to take full advantage of their unique characteristics while overcoming their complex errors and modalities. Here, we discuss several of the most important applications of the new technologies, focusing on both the currently available bioinformatics tools and opportunities for future research.}, } @article {pmid29599459, year = {2018}, author = {Zengler, K and Zaramela, LS}, title = {The social network of microorganisms - how auxotrophies shape complex communities.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {383-390}, pmid = {29599459}, issn = {1740-1534}, support = {R21 AR071731/AR/NIAMS NIH HHS/United States ; }, abstract = {Microorganisms engage in complex interactions with other organisms and their environment. Recent studies have shown that these interactions are not limited to the exchange of electron donors. Most microorganisms are auxotrophs, thus relying on external nutrients for growth, including the exchange of amino acids and vitamins. Currently, we lack a deeper understanding of auxotrophies in microorganisms and how nutrient requirements differ between different strains and different environments. In this Opinion article, we describe how the study of auxotrophies and nutrient requirements among members of complex communities will enable new insights into community composition and assembly. Understanding this complex network over space and time is crucial for developing strategies to interrogate and shape microbial communities.}, } @article {pmid29599458, year = {2018}, author = {Shapiro, RS and Chavez, A and Collins, JJ}, title = {CRISPR-based genomic tools for the manipulation of genetically intractable microorganisms.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {333-339}, doi = {10.1038/s41579-018-0002-7}, pmid = {29599458}, issn = {1740-1534}, abstract = {Genetic manipulation of microorganisms has been crucial in understanding their biology, yet for many microbial species, robust tools for comprehensive genetic analysis were lacking until the advent of CRISPR-Cas-based gene editing techniques. In this Progress article, we discuss advances in CRISPR-based techniques for the genetic analysis of genetically intractable microorganisms, with an emphasis on mycobacteria, fungi and parasites. We discuss how CRISPR-based analyses in these organisms have enabled the discovery of novel gene functions, the investigation of genetic interaction networks and the identification of virulence factors.}, } @article {pmid29599457, year = {2018}, author = {Weiser, JN and Ferreira, DM and Paton, JC}, title = {Streptococcus pneumoniae: transmission, colonization and invasion.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {355-367}, pmid = {29599457}, issn = {1740-1534}, support = {R01 AI038446/AI/NIAID NIH HHS/United States ; R01 AI105168/AI/NIAID NIH HHS/United States ; }, abstract = {Streptococcus pneumoniae has a complex relationship with its obligate human host. On the one hand, the pneumococci are highly adapted commensals, and their main reservoir on the mucosal surface of the upper airways of carriers enables transmission. On the other hand, they can cause severe disease when bacterial and host factors allow them to invade essentially sterile sites, such as the middle ear spaces, lungs, bloodstream and meninges. Transmission, colonization and invasion depend on the remarkable ability of S. pneumoniae to evade or take advantage of the host inflammatory and immune responses. The different stages of pneumococcal carriage and disease have been investigated in detail in animal models and, more recently, in experimental human infection. Furthermore, widespread vaccination and the resulting immune pressure have shed light on pneumococcal population dynamics and pathogenesis. Here, we review the mechanistic insights provided by these studies on the multiple and varied interactions of the pneumococcus and its host.}, } @article {pmid29599456, year = {2018}, author = {Hofer, U}, title = {To grow, or not to grow.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {329}, doi = {10.1038/s41579-018-0006-3}, pmid = {29599456}, issn = {1740-1534}, } @article {pmid29599248, year = {2018}, author = {Nording, ML}, title = {Figuring out how I belong.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1558}, doi = {10.1126/science.359.6383.1558}, pmid = {29599248}, issn = {1095-9203}, } @article {pmid29599247, year = {2018}, author = {Petrie, KL and Palmer, ND and Johnson, DT and Medina, SJ and Yan, SJ and Li, V and Burmeister, AR and Meyer, JR}, title = {Destabilizing mutations encode nongenetic variation that drives evolutionary innovation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1542-1545}, doi = {10.1126/science.aar1954}, pmid = {29599247}, issn = {1095-9203}, mesh = {Bacterial Outer Membrane Proteins/genetics ; Bacteriophage lambda/*genetics ; *Evolution, Molecular ; *Genetic Fitness ; *Genetic Variation ; Mutation ; Porins/genetics ; Receptors, Virus/genetics ; Viral Tail Proteins/genetics ; }, abstract = {Evolutionary innovations are often achieved by repurposing existing genes to perform new functions; however, the mechanisms enabling the transition from old to new remain controversial. We identified mutations in bacteriophage λ's host-recognition gene J that confer enhanced adsorption to λ's native receptor, LamB, and the ability to access a new receptor, OmpF. The mutations destabilize λ particles and cause conformational bistability of J, which yields progeny of multiple phenotypic forms, each proficient at different receptors. This work provides an example of how nongenetic protein variation can catalyze an evolutionary innovation. We propose that cases where a single genotype can manifest as multiple phenotypes may be more common than previously expected and offer a general mechanism for evolutionary innovation.}, } @article {pmid29599246, year = {2018}, author = {Ferrari de Andrade, L and Tay, RE and Pan, D and Luoma, AM and Ito, Y and Badrinath, S and Tsoucas, D and Franz, B and May, KF and Harvey, CJ and Kobold, S and Pyrdol, JW and Yoon, C and Yuan, GC and Hodi, FS and Dranoff, G and Wucherpfennig, KW}, title = {Antibody-mediated inhibition of MICA and MICB shedding promotes NK cell-driven tumor immunity.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1537-1542}, doi = {10.1126/science.aao0505}, pmid = {29599246}, issn = {1095-9203}, support = {T32 CA207021/CA/NCI NIH HHS/United States ; R01 CA173750/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Blocking/immunology/*therapeutic use ; Antibodies, Monoclonal/immunology/*therapeutic use ; Histocompatibility Antigens Class I/chemistry/*immunology ; Humans ; Immunocompetence ; Killer Cells, Natural/*immunology ; Ligands ; Melanoma/immunology/pathology/*therapy ; Melanoma, Experimental/immunology/pathology/therapy ; Mice ; Mice, Inbred C57BL ; NK Cell Lectin-Like Receptor Subfamily K/immunology ; Neoplasm Metastasis ; Protein Domains/immunology ; Receptors, IgG/immunology ; }, abstract = {MICA and MICB are expressed by many human cancers as a result of cellular stress, and can tag cells for elimination by cytotoxic lymphocytes through natural killer group 2D (NKG2D) receptor activation. However, tumors evade this immune recognition pathway through proteolytic shedding of MICA and MICB proteins. We rationally designed antibodies targeting the MICA α3 domain, the site of proteolytic shedding, and found that these antibodies prevented loss of cell surface MICA and MICB by human cancer cells. These antibodies inhibited tumor growth in multiple fully immunocompetent mouse models and reduced human melanoma metastases in a humanized mouse model. Antitumor immunity was mediated mainly by natural killer (NK) cells through activation of NKG2D and CD16 Fc receptors. This approach prevents the loss of important immunostimulatory ligands by human cancers and reactivates antitumor immunity.}, } @article {pmid29599245, year = {2018}, author = {Zyryanova, AF and Weis, F and Faille, A and Alard, AA and Crespillo-Casado, A and Sekine, Y and Harding, HP and Allen, F and Parts, L and Fromont, C and Fischer, PM and Warren, AJ and Ron, D}, title = {Binding of ISRIB reveals a regulatory site in the nucleotide exchange factor eIF2B.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1533-1536}, pmid = {29599245}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; MC_U105161083//Medical Research Council/United Kingdom ; MR/L003368/1//Medical Research Council/United Kingdom ; //Medical Research Council/United Kingdom ; }, mesh = {Acetamides/*chemistry/pharmacology ; Animals ; Cryoelectron Microscopy ; Cyclohexylamines/*chemistry/pharmacology ; Eukaryotic Initiation Factor-2B/*chemistry/genetics ; HeLa Cells ; Humans ; Mice ; Mutagenesis ; Phosphorylation ; Protein Binding ; Protein Biosynthesis/drug effects ; Protein Conformation ; Stress, Physiological/drug effects ; }, abstract = {The integrated stress response (ISR) is a conserved translational and transcriptional program affecting metabolism, memory, and immunity. The ISR is mediated by stress-induced phosphorylation of eukaryotic translation initiation factor 2α (eIF2α) that attenuates the guanine nucleotide exchange factor eIF2B. A chemical inhibitor of the ISR, ISRIB, reverses the attenuation of eIF2B by phosphorylated eIF2α, protecting mice from neurodegeneration and traumatic brain injury. We describe a 4.1-angstrom-resolution cryo-electron microscopy structure of human eIF2B with an ISRIB molecule bound at the interface between the β and δ regulatory subunits. Mutagenesis of residues lining this pocket altered the hierarchical cellular response to ISRIB analogs in vivo and ISRIB binding in vitro. Our findings point to a site in eIF2B that can be exploited by ISRIB to regulate translation.}, } @article {pmid29599244, year = {2018}, author = {Milles, LF and Schulten, K and Gaub, HE and Bernardi, RC}, title = {Molecular mechanism of extreme mechanostability in a pathogen adhesin.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1527-1533}, doi = {10.1126/science.aar2094}, pmid = {29599244}, issn = {1095-9203}, support = {P41 GM104601/GM/NIGMS NIH HHS/United States ; //European Research Council/International ; }, mesh = {Adhesins, Bacterial/*chemistry ; Bacterial Proteins/*chemistry ; Carrier Proteins/*chemistry ; Fibrinogen/chemistry ; Humans ; Hydrogen Bonding ; Microscopy, Atomic Force ; Molecular Dynamics Simulation ; Phenylalanine/chemistry ; Single-Cell Analysis ; *Stress, Mechanical ; }, abstract = {High resilience to mechanical stress is key when pathogens adhere to their target and initiate infection. Using atomic force microscopy-based single-molecule force spectroscopy, we explored the mechanical stability of the prototypical staphylococcal adhesin SdrG, which targets a short peptide from human fibrinogen β. Steered molecular dynamics simulations revealed, and single-molecule force spectroscopy experiments confirmed, the mechanism by which this complex withstands forces of over 2 nanonewtons, a regime previously associated with the strength of a covalent bond. The target peptide, confined in a screwlike manner in the binding pocket of SdrG, distributes forces mainly toward the peptide backbone through an intricate hydrogen bond network. Thus, these adhesins can attach to their target with exceptionally resilient mechanostability, virtually independent of peptide side chains.}, } @article {pmid29599243, year = {2018}, author = {Zhang, DL and Wu, J and Shah, BN and Greutélaers, KC and Ghosh, MC and Ollivierre, H and Su, XZ and Thuma, PE and Bedu-Addo, G and Mockenhaupt, FP and Gordeuk, VR and Rouault, TA}, title = {Erythrocytic ferroportin reduces intracellular iron accumulation, hemolysis, and malaria risk.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1520-1523}, doi = {10.1126/science.aal2022}, pmid = {29599243}, issn = {1095-9203}, mesh = {African Continental Ancestry Group/genetics ; Amino Acid Substitution ; Anemia/metabolism ; Animals ; Cation Transport Proteins/genetics/*metabolism ; Child ; Erythrocytes/drug effects/*metabolism ; Female ; *Hemolysis ; Hepcidins/metabolism/pharmacology ; Humans ; Iron/administration & dosage/*metabolism/pharmacology ; Malaria/blood/*epidemiology/genetics ; Male ; Mice ; Mice, Knockout ; Mutation ; Oxidative Stress ; Risk ; Selection, Genetic ; Sequence Deletion ; Zambia/epidemiology ; }, abstract = {Malaria parasites invade red blood cells (RBCs), consume copious amounts of hemoglobin, and severely disrupt iron regulation in humans. Anemia often accompanies malaria disease; however, iron supplementation therapy inexplicably exacerbates malarial infections. Here we found that the iron exporter ferroportin (FPN) was highly abundant in RBCs, and iron supplementation suppressed its activity. Conditional deletion of the Fpn gene in erythroid cells resulted in accumulation of excess intracellular iron, cellular damage, hemolysis, and increased fatality in malaria-infected mice. In humans, a prevalent FPN mutation, Q248H (glutamine to histidine at position 248), prevented hepcidin-induced degradation of FPN and protected against severe malaria disease. FPN Q248H appears to have been positively selected in African populations in response to the impact of malaria disease. Thus, FPN protects RBCs against oxidative stress and malaria infection.}, } @article {pmid29599242, year = {2018}, author = {Voyles, J and Woodhams, DC and Saenz, V and Byrne, AQ and Perez, R and Rios-Sotelo, G and Ryan, MJ and Bletz, MC and Sobell, FA and McLetchie, S and Reinert, L and Rosenblum, EB and Rollins-Smith, LA and Ibáñez, R and Ray, JM and Griffith, EJ and Ross, H and Richards-Zawacki, CL}, title = {Shifts in disease dynamics in a tropical amphibian assemblage are not due to pathogen attenuation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1517-1519}, doi = {10.1126/science.aao4806}, pmid = {29599242}, issn = {1095-9203}, mesh = {Animal Diseases/*microbiology ; Animals ; Anura/*microbiology ; Chytridiomycota/*pathogenicity ; Communicable Diseases/*epidemiology ; *Disease Outbreaks ; *Host-Pathogen Interactions ; *Models, Biological ; Panama ; }, abstract = {Infectious diseases rarely end in extinction. Yet the mechanisms that explain how epidemics subside are difficult to pinpoint. We investigated host-pathogen interactions after the emergence of a lethal fungal pathogen in a tropical amphibian assemblage. Some amphibian host species are recovering, but the pathogen is still present and is as pathogenic today as it was almost a decade ago. In addition, some species have defenses that are more effective now than they were before the epidemic. These results suggest that host recoveries are not caused by pathogen attenuation and may be due to shifts in host responses. Our findings provide insights into the mechanisms underlying disease transitions, which are increasingly important to understand in an era of emerging infectious diseases and unprecedented global pandemics.}, } @article {pmid29599241, year = {2018}, author = {Li, L and Basu, S and Wang, Y and Chen, Z and Hundekar, P and Wang, B and Shi, J and Shi, Y and Narayanan, S and Koratkar, N}, title = {Self-heating-induced healing of lithium dendrites.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1513-1516}, doi = {10.1126/science.aap8787}, pmid = {29599241}, issn = {1095-9203}, abstract = {Lithium (Li) metal electrodes are not deployable in rechargeable batteries because electrochemical plating and stripping invariably leads to growth of dendrites that reduce coulombic efficiency and eventually short the battery. It is generally accepted that the dendrite problem is exacerbated at high current densities. Here, we report a regime for dendrite evolution in which the reverse is true. In our experiments, we found that when the plating and stripping current density is raised above ~9 milliamperes per square centimeter, there is substantial self-heating of the dendrites, which triggers extensive surface migration of Li. This surface diffusion heals the dendrites and smoothens the Li metal surface. We show that repeated doses of high-current-density healing treatment enables the safe cycling of Li-sulfur batteries with high coulombic efficiency.}, } @article {pmid29599240, year = {2018}, author = {Vatankhah-Varnosfaderani, M and Keith, AN and Cong, Y and Liang, H and Rosenthal, M and Sztucki, M and Clair, C and Magonov, S and Ivanov, DA and Dobrynin, AV and Sheiko, SS}, title = {Chameleon-like elastomers with molecularly encoded strain-adaptive stiffening and coloration.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1509-1513}, doi = {10.1126/science.aar5308}, pmid = {29599240}, issn = {1095-9203}, abstract = {Active camouflage is widely recognized as a soft-tissue feature, and yet the ability to integrate adaptive coloration and tissuelike mechanical properties into synthetic materials remains elusive. We provide a solution to this problem by uniting these functions in moldable elastomers through the self-assembly of linear-bottlebrush-linear triblock copolymers. Microphase separation of the architecturally distinct blocks results in physically cross-linked networks that display vibrant color, extreme softness, and intense strain stiffening on par with that of skin tissue. Each of these functional properties is regulated by the structure of one macromolecule, without the need for chemical cross-linking or additives. These materials remain stable under conditions characteristic of internal bodily environments and under ambient conditions, neither swelling in bodily fluids nor drying when exposed to air.}, } @article {pmid29599239, year = {2018}, author = {Skaug, MJ and Schwemmer, C and Fringes, S and Rawlings, CD and Knoll, AW}, title = {Nanofluidic rocking Brownian motors.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1505-1508}, doi = {10.1126/science.aal3271}, pmid = {29599239}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Control and transport of nanoscale objects in fluids is challenging because of the unfavorable scaling of most interaction mechanisms to small length scales. We designed energy landscapes for nanoparticles by accurately shaping the geometry of a nanofluidic slit and exploiting the electrostatic interaction between like-charged particles and walls. Directed transport was performed by combining asymmetric potentials with an oscillating electric field to achieve a rocking Brownian motor. Using gold spheres 60 nanometers in diameter, we investigated the physics of the motor with high spatiotemporal resolution, enabling a parameter-free comparison with theory. We fabricated a sorting device that separates 60- and 100-nanometer particles in opposing directions within seconds. Modeling suggests that the device separates particles with a radial difference of 1 nanometer.}, } @article {pmid29599238, year = {2018}, author = {Tsuji, N and Kennemur, JL and Buyck, T and Lee, S and Prévost, S and Kaib, PSJ and Bykov, D and Farès, C and List, B}, title = {Activation of olefins via asymmetric Brønsted acid catalysis.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1501-1505}, doi = {10.1126/science.aaq0445}, pmid = {29599238}, issn = {1095-9203}, abstract = {The activation of olefins for asymmetric chemical synthesis traditionally relies on transition metal catalysts. In contrast, biological enzymes with Brønsted acidic sites of appropriate strength can protonate olefins and thereby generate carbocations that ultimately react to form natural products. Although chemists have recently designed chiral Brønsted acid catalysts to activate imines and carbonyl compounds, mimicking these enzymes to protonate simple olefins that then engage in asymmetric catalytic reactions has remained a substantial synthetic challenge. Here, we show that a class of confined and strong chiral Brønsted acids enables the catalytic asymmetric intramolecular hydroalkoxylation of unbiased olefins. The methodology gives rapid access to biologically active 1,1-disubstituted tetrahydrofurans, including (-)-Boivinianin A.}, } @article {pmid29599237, year = {2018}, author = {Xu, C and Stiubianu, GT and Gorodetsky, AA}, title = {Adaptive infrared-reflecting systems inspired by cephalopods.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1495-1500}, doi = {10.1126/science.aar5191}, pmid = {29599237}, issn = {1095-9203}, abstract = {Materials and systems that statically reflect radiation in the infrared region of the electromagnetic spectrum underpin the performance of many entrenched technologies, including building insulation, energy-conserving windows, spacecraft components, electronics shielding, container packaging, protective clothing, and camouflage platforms. The development of their adaptive variants, in which the infrared-reflecting properties dynamically change in response to external stimuli, has emerged as an important unmet scientific challenge. By drawing inspiration from cephalopod skin, we developed adaptive infrared-reflecting platforms that feature a simple actuation mechanism, low working temperature, tunable spectral range, weak angular dependence, fast response, stability to repeated cycling, amenability to patterning and multiplexing, autonomous operation, robust mechanical properties, and straightforward manufacturability. Our findings may open opportunities for infrared camouflage and other technologies that regulate infrared radiation.}, } @article {pmid29599236, year = {2018}, author = {Yao, Y and Huang, Z and Xie, P and Lacey, SD and Jacob, RJ and Xie, H and Chen, F and Nie, A and Pu, T and Rehwoldt, M and Yu, D and Zachariah, MR and Wang, C and Shahbazian-Yassar, R and Li, J and Hu, L}, title = {Carbothermal shock synthesis of high-entropy-alloy nanoparticles.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1489-1494}, doi = {10.1126/science.aan5412}, pmid = {29599236}, issn = {1095-9203}, abstract = {The controllable incorporation of multiple immiscible elements into a single nanoparticle merits untold scientific and technological potential, yet remains a challenge using conventional synthetic techniques. We present a general route for alloying up to eight dissimilar elements into single-phase solid-solution nanoparticles, referred to as high-entropy-alloy nanoparticles (HEA-NPs), by thermally shocking precursor metal salt mixtures loaded onto carbon supports [temperature ~2000 kelvin (K), 55-millisecond duration, rate of ~105 K per second]. We synthesized a wide range of multicomponent nanoparticles with a desired chemistry (composition), size, and phase (solid solution, phase-separated) by controlling the carbothermal shock (CTS) parameters (substrate, temperature, shock duration, and heating/cooling rate). To prove utility, we synthesized quinary HEA-NPs as ammonia oxidation catalysts with ~100% conversion and >99% nitrogen oxide selectivity over prolonged operations.}, } @article {pmid29599235, year = {2018}, author = {Sippel, D and Rohde, M and Netzer, J and Trncik, C and Gies, J and Grunau, K and Djurdjevic, I and Decamps, L and Andrade, SLA and Einsle, O}, title = {A bound reaction intermediate sheds light on the mechanism of nitrogenase.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1484-1489}, doi = {10.1126/science.aar2765}, pmid = {29599235}, issn = {1095-9203}, mesh = {Binding Sites ; *Biocatalysis ; Carbon Monoxide/chemistry ; Catalytic Domain ; Hydrogen Bonding ; Ligands ; Molybdenum/chemistry ; Nitrogen/*chemistry ; Nitrogenase/*chemistry ; Oxidation-Reduction ; }, abstract = {Reduction of N2 by nitrogenases occurs at an organometallic iron cofactor that commonly also contains either molybdenum or vanadium. The well-characterized resting state of the cofactor does not bind substrate, so its mode of action remains enigmatic. Carbon monoxide was recently found to replace a bridging sulfide, but the mechanistic relevance was unclear. Here we report the structural analysis of vanadium nitrogenase with a bound intermediate, interpreted as a μ2-bridging, protonated nitrogen that implies the site and mode of substrate binding to the cofactor. Binding results in a flip of amino acid glutamine 176, which hydrogen-bonds the ligand and creates a holding position for the displaced sulfide. The intermediate likely represents state E6 or E7 of the Thorneley-Lowe model and provides clues to the remainder of the catalytic cycle.}, } @article {pmid29599234, year = {2018}, author = {Earle, SA and Wright, DJ and Joye, S and Laffoley, D and Baxter, J and Safina, C and Elkus, P}, title = {Ocean deoxygenation: Time for action.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1475-1476}, doi = {10.1126/science.aat0167}, pmid = {29599234}, issn = {1095-9203}, mesh = {*Global Warming ; Oceans and Seas ; Oxygen/analysis ; *Seawater ; }, } @article {pmid29599233, year = {2018}, author = {Pérez-Escobar, OA and Cámara-Leret, R and Antonelli, A and Bateman, R and Bellot, S and Chomicki, G and Cleef, A and Diazgranados, M and Dodsworth, S and Jaramillo, C and Madriñan, S and Olivares, I and Zuluaga, A and Bernal, R}, title = {Mining threatens Colombian ecosystems.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1475}, doi = {10.1126/science.aat4849}, pmid = {29599233}, issn = {1095-9203}, mesh = {*Biodiversity ; Colombia ; Environmental Monitoring ; *Mining ; }, } @article {pmid29599232, year = {2018}, author = {Stains, M and Harshman, J and Barker, MK and Chasteen, SV and Cole, R and DeChenne-Peters, SE and Eagan, MK and Esson, JM and Knight, JK and Laski, FA and Levis-Fitzgerald, M and Lee, CJ and Lo, SM and McDonnell, LM and McKay, TA and Michelotti, N and Musgrove, A and Palmer, MS and Plank, KM and Rodela, TM and Sanders, ER and Schimpf, NG and Schulte, PM and Smith, MK and Stetzer, M and Van Valkenburgh, B and Vinson, E and Weir, LK and Wendel, PJ and Wheeler, LB and Young, AM}, title = {Anatomy of STEM teaching in North American universities.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1468-1470}, doi = {10.1126/science.aap8892}, pmid = {29599232}, issn = {1095-9203}, support = {R25 GM114822/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, } @article {pmid29599231, year = {2018}, author = {Skrabalak, SE}, title = {Mashing up metals with carbothermal shock.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1467}, doi = {10.1126/science.aat1471}, pmid = {29599231}, issn = {1095-9203}, } @article {pmid29599230, year = {2018}, author = {Veiga-Fernandes, H and Artis, D}, title = {Neuronal-immune system cross-talk in homeostasis.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1465-1466}, doi = {10.1126/science.aap9598}, pmid = {29599230}, issn = {1095-9203}, support = {R01 AI061570/AI/NIAID NIH HHS/United States ; R21 AI087990/AI/NIAID NIH HHS/United States ; R01 AI074878/AI/NIAID NIH HHS/United States ; R21 AI083480/AI/NIAID NIH HHS/United States ; R01 AI095466/AI/NIAID NIH HHS/United States ; U01 AI095608/AI/NIAID NIH HHS/United States ; R01 AI102942/AI/NIAID NIH HHS/United States ; R01 AI097333/AI/NIAID NIH HHS/United States ; //European Research Council/International ; }, mesh = {Animals ; Cell Communication ; *Homeostasis ; Humans ; Immune System/*cytology ; *Neuroimmunomodulation ; Neurons/*immunology ; }, } @article {pmid29599229, year = {2018}, author = {Herman-Bausier, P and Dufrêne, YF}, title = {Force matters in hospital-acquired infections.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1464-1465}, doi = {10.1126/science.aat3764}, pmid = {29599229}, issn = {1095-9203}, mesh = {*Community-Acquired Infections ; *Cross Infection ; Humans ; }, } @article {pmid29599228, year = {2018}, author = {Mukhopadhyay, A and Jangid, MK}, title = {Li metal battery, heal thyself.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1463}, doi = {10.1126/science.aat2452}, pmid = {29599228}, issn = {1095-9203}, } @article {pmid29599227, year = {2018}, author = {Draguhn, A}, title = {Making room for new memories.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1461-1462}, doi = {10.1126/science.aat1493}, pmid = {29599227}, issn = {1095-9203}, mesh = {Humans ; *Memory, Episodic ; *Mental Recall ; }, } @article {pmid29599226, year = {2018}, author = {Cerwenka, A and Lanier, LL}, title = {Natural killers join the fight against cancer.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1460-1461}, doi = {10.1126/science.aat2184}, pmid = {29599226}, issn = {1095-9203}, mesh = {Humans ; *Killer Cells, Natural ; *Neoplasms ; }, } @article {pmid29599225, year = {2018}, author = {Collins, JP}, title = {Change is key to frog survival.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1458-1459}, doi = {10.1126/science.aat1996}, pmid = {29599225}, issn = {1095-9203}, mesh = {Animals ; *Anura ; *Ranidae ; }, } @article {pmid29599224, year = {2018}, author = {Leslie, M}, title = {Putting immune cells on a diet.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1454-1456}, doi = {10.1126/science.359.6383.1454}, pmid = {29599224}, issn = {1095-9203}, mesh = {Autoimmune Diseases/*drug therapy ; *Drug Discovery ; Humans ; Immune System/*drug effects/*metabolism ; }, } @article {pmid29599223, year = {2018}, author = {Clery, D}, title = {New missions aim to make a short list of exo-Earths.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1453}, doi = {10.1126/science.359.6383.1453}, pmid = {29599223}, issn = {1095-9203}, } @article {pmid29599222, year = {2018}, author = {Chen, S}, title = {X-ray 'ghost images' could cut radiation doses.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1452}, doi = {10.1126/science.359.6383.1452}, pmid = {29599222}, issn = {1095-9203}, mesh = {China ; Diagnostic Imaging/*instrumentation ; Humans ; *Radiation Dosage ; X-Rays ; }, } @article {pmid29599221, year = {2018}, author = {Voosen, P}, title = {Meteorite divide points to solar system chaos.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1451}, doi = {10.1126/science.359.6383.1451}, pmid = {29599221}, issn = {1095-9203}, } @article {pmid29599220, year = {2018}, author = {Cohen, J}, title = {U.S. blames 'massive' hack of research data on Iran.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1450}, doi = {10.1126/science.359.6383.1450}, pmid = {29599220}, issn = {1095-9203}, } @article {pmid29599219, year = {2018}, author = {Warren, M}, title = {U.K. trials of airway transplants are in limbo.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1448-1450}, doi = {10.1126/science.359.6383.1448}, pmid = {29599219}, issn = {1095-9203}, mesh = {Humans ; Regeneration ; Regenerative Medicine/*ethics ; *Scientific Misconduct ; Stem Cells ; *Tissue Engineering ; Trachea/*physiology/*surgery ; Transplants ; }, } @article {pmid29599218, year = {2018}, author = {Mervis, J}, title = {Congress gives science a record funding boost.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1447-1448}, doi = {10.1126/science.359.6383.1447}, pmid = {29599218}, issn = {1095-9203}, } @article {pmid29599217, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1444-1446}, doi = {10.1126/science.359.6383.1444}, pmid = {29599217}, issn = {1095-9203}, } @article {pmid29599216, year = {2018}, author = {Sundin, J and Jutfelt, F}, title = {Keeping science honest.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1443}, doi = {10.1126/science.aat3473}, pmid = {29599216}, issn = {1095-9203}, } @article {pmid29599215, year = {2018}, author = {Horner, A and Pohl, P}, title = {Comment on "Enhanced water permeability and tunable ion selectivity in subnanometer carbon nanotube porins".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {}, doi = {10.1126/science.aap9173}, pmid = {29599215}, issn = {1095-9203}, mesh = {Aquaporins ; *Nanotubes, Carbon ; Permeability ; *Porins ; Water ; }, abstract = {Tunuguntla et al (Reports, 25 August 2017, p. 792) report that permeation of single-file water occurs faster through carbon nanotubes than through aquaporins. We show that this conclusion violates fundamental thermodynamic laws: Because of its much lower activation energy, aquaporin-mediated water transport must be orders of magnitude faster. Leakage at the nanotube-membrane interface may explain the discrepancy.}, } @article {pmid29599214, year = {2018}, author = {Tunuguntla, RH and Zhang, Y and Henley, RY and Yao, YC and Pham, TA and Wanunu, M and Noy, A}, title = {Response to Comment on "Enhanced water permeability and tunable ion selectivity in subnanometer carbon nanotube porins".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {}, doi = {10.1126/science.aaq1241}, pmid = {29599214}, issn = {1095-9203}, mesh = {Biological Transport ; *Nanotubes, Carbon ; Permeability ; *Porins ; Water ; }, abstract = {Horner and Pohl argue that high water transport rates reported for carbon nanotube porins (CNTPs) originate from leakage at the nanotube-bilayer interface. Our results and new experimental evidence are consistent with transport through the nanotube pores and rule out a defect-mediated transport mechanism. Mechanistic origins of the high Arrhenius factor that we reported for narrow CNTPs at pH 8 require further investigation.}, } @article {pmid29599213, year = {2018}, author = {Tsai, JC and Miller-Vedam, LE and Anand, AA and Jaishankar, P and Nguyen, HC and Renslo, AR and Frost, A and Walter, P}, title = {Structure of the nucleotide exchange factor eIF2B reveals mechanism of memory-enhancing molecule.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {}, pmid = {29599213}, issn = {1095-9203}, support = {DP2 GM110772/GM/NIGMS NIH HHS/United States ; S10 OD020054/OD/NIH HHS/United States ; S10 OD021596/OD/NIH HHS/United States ; S10 OD021741/OD/NIH HHS/United States ; }, mesh = {Acetamides/*chemistry/*pharmacology ; Cryoelectron Microscopy ; Cyclohexylamines/*chemistry/*pharmacology ; Escherichia coli ; Eukaryotic Initiation Factor-2B/*chemistry/genetics/ultrastructure ; Humans ; Memory/*drug effects ; Mutation ; Nootropic Agents/*chemistry/*pharmacology ; Phosphorylation ; Protein Conformation ; Protein Folding ; Protein Multimerization/drug effects ; Protein Stability/drug effects ; Recombinant Proteins/chemistry/genetics/ultrastructure ; }, abstract = {Regulation by the integrated stress response (ISR) converges on the phosphorylation of translation initiation factor eIF2 in response to a variety of stresses. Phosphorylation converts eIF2 from a substrate to a competitive inhibitor of its dedicated guanine nucleotide exchange factor, eIF2B, thereby inhibiting translation. ISRIB, a drug-like eIF2B activator, reverses the effects of eIF2 phosphorylation, and in rodents it enhances cognition and corrects cognitive deficits after brain injury. To determine its mechanism of action, we solved an atomic-resolution structure of ISRIB bound in a deep cleft within decameric human eIF2B by cryo-electron microscopy. Formation of fully active, decameric eIF2B holoenzyme depended on the assembly of two identical tetrameric subcomplexes, and ISRIB promoted this step by cross-bridging a central symmetry interface. Thus, regulation of eIF2B assembly emerges as a rheostat for eIF2B activity that tunes translation during the ISR and that can be further modulated by ISRIB.}, } @article {pmid29599194, year = {2018}, author = {Kornberg, MD and Bhargava, P and Kim, PM and Putluri, V and Snowman, AM and Putluri, N and Calabresi, PA and Snyder, SH}, title = {Dimethyl fumarate targets GAPDH and aerobic glycolysis to modulate immunity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {449-453}, pmid = {29599194}, issn = {1095-9203}, support = {R01 CA220297/CA/NCI NIH HHS/United States ; R37 NS041435/NS/NINDS NIH HHS/United States ; R37 MH018501/MH/NIMH NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; R01 MH018501/MH/NIMH NIH HHS/United States ; R01 CA216426/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases/drug therapy/enzymology ; Autoimmunity/*drug effects ; Citric Acid Cycle ; Cysteine/metabolism ; Dimethyl Fumarate/*pharmacology/therapeutic use ; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating)/*metabolism ; Glycolysis/*drug effects ; Humans ; Immunosuppressive Agents/*pharmacology/therapeutic use ; Lymphocytes/drug effects/enzymology/immunology ; Mice ; Mice, Inbred C57BL ; Myeloid Cells/drug effects/enzymology/immunology ; Succinates/chemistry ; }, abstract = {Activated immune cells undergo a metabolic switch to aerobic glycolysis akin to the Warburg effect, thereby presenting a potential therapeutic target in autoimmune disease. Dimethyl fumarate (DMF), a derivative of the Krebs cycle intermediate fumarate, is an immunomodulatory drug used to treat multiple sclerosis and psoriasis. Although its therapeutic mechanism remains uncertain, DMF covalently modifies cysteine residues in a process termed succination. We found that DMF succinates and inactivates the catalytic cysteine of the glycolytic enzyme glyceraldehyde 3-phosphate dehydrogenase (GAPDH) in mice and humans, both in vitro and in vivo. It thereby down-regulates aerobic glycolysis in activated myeloid and lymphoid cells, which mediates its anti-inflammatory effects. Our results provide mechanistic insight into immune modulation by DMF and represent a proof of concept that aerobic glycolysis is a therapeutic target in autoimmunity.}, } @article {pmid29599193, year = {2018}, author = {Sui, P and Wiesner, DL and Xu, J and Zhang, Y and Lee, J and Van Dyken, S and Lashua, A and Yu, C and Klein, BS and Locksley, RM and Deutsch, G and Sun, X}, title = {Pulmonary neuroendocrine cells amplify allergic asthma responses.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6393}, pages = {}, doi = {10.1126/science.aan8546}, pmid = {29599193}, issn = {1095-9203}, support = {P01 HL107202/HL/NHLBI NIH HHS/United States ; R01 HL142215/HL/NHLBI NIH HHS/United States ; R01 HL119946/HL/NHLBI NIH HHS/United States ; R01 HL113870/HL/NHLBI NIH HHS/United States ; R01 HL143256/HL/NHLBI NIH HHS/United States ; R01 HL122406/HL/NHLBI NIH HHS/United States ; R01 AI040996/AI/NIAID NIH HHS/United States ; OT2 OD023857/OD/NIH HHS/United States ; }, mesh = {Animals ; Asthma/*immunology/*pathology ; Basic Helix-Loop-Helix Transcription Factors/deficiency/genetics ; Calcitonin Gene-Related Peptide/metabolism ; Cytokines/biosynthesis ; Disease Models, Animal ; Epithelial Cells/immunology/pathology ; Female ; Goblet Cells/pathology ; Humans ; Hyperplasia ; Lung/*pathology ; Mice ; Neuroendocrine Cells/*immunology/*pathology ; gamma-Aminobutyric Acid/biosynthesis/metabolism ; }, abstract = {Pulmonary neuroendocrine cells (PNECs) are rare airway epithelial cells whose function is poorly understood. Here we show that Ascl1-mutant mice that have no PNECs exhibit severely blunted mucosal type 2 response in models of allergic asthma. PNECs reside in close proximity to group 2 innate lymphoid cells (ILC2s) near airway branch points. PNECs act through calcitonin gene-related peptide (CGRP) to stimulate ILC2s and elicit downstream immune responses. In addition, PNECs act through the neurotransmitter γ-aminobutyric acid (GABA) to induce goblet cell hyperplasia. The instillation of a mixture of CGRP and GABA in Ascl1-mutant airways restores both immune and goblet cell responses. In accordance, lungs from human asthmatics show increased PNECs. These findings demonstrate that the PNEC-ILC2 neuroimmunological modules function at airway branch points to amplify allergic asthma responses.}, } @article {pmid29599192, year = {2018}, author = {Weng, Q and Komiyama, S and Yang, L and An, Z and Chen, P and Biehs, SA and Kajihara, Y and Lu, W}, title = {Imaging of nonlocal hot-electron energy dissipation via shot noise.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6390}, pages = {775-778}, doi = {10.1126/science.aam9991}, pmid = {29599192}, issn = {1095-9203}, abstract = {In modern microelectronic devices, hot electrons accelerate, scatter, and dissipate energy in nanoscale dimensions. Despite recent progress in nanothermometry, direct real-space mapping of hot-electron energy dissipation is challenging because existing techniques are restricted to probing the lattice rather than the electrons. We realize electronic nanothermometry by measuring local current fluctuations, or shot noise, associated with ultrafast hot-electron kinetic processes (~21 terahertz). Exploiting a scanning and contact-free tungsten tip as a local noise probe, we directly visualize hot-electron distributions before their thermal equilibration with the host gallium arsenide/aluminium gallium arsenide crystal lattice. With nanoconstriction devices, we reveal unexpected nonlocal energy dissipation at room temperature, which is reminiscent of ballistic transport of low-temperature quantum conductors.}, } @article {pmid29599125, year = {2018}, author = {Ma, H and Wert, KJ and Shvartsman, D and Melton, DA and Jaenisch, R}, title = {Establishment of human pluripotent stem cell-derived pancreatic β-like cells in the mouse pancreas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3924-3929}, pmid = {29599125}, issn = {1091-6490}, support = {R01 MH104610/MH/NIMH NIH HHS/United States ; R01 GM114864/GM/NIGMS NIH HHS/United States ; R01 NS088538/NS/NINDS NIH HHS/United States ; R37 HD045022/HD/NICHD NIH HHS/United States ; RF1 AG048029/AG/NIA NIH HHS/United States ; R01 CA084198/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Acinar Cells/metabolism ; Animals ; Cell Differentiation ; Cell Proliferation ; Cell- and Tissue-Based Therapy ; Cells, Cultured ; Diabetes Mellitus, Type 1/metabolism/physiopathology/*therapy ; Glucose/metabolism ; Humans ; Insulin/metabolism ; Insulin Secretion ; Insulin-Secreting Cells/*cytology/metabolism/transplantation ; Mice ; Pancreas/*cytology/metabolism ; Pluripotent Stem Cells/cytology/metabolism/*transplantation ; }, abstract = {Type 1 diabetes is characterized by autoimmune destruction of β cells located in pancreatic islets. However, tractable in vivo models of human pancreatic β cells have been limited. Here, we generated xenogeneic human pancreatic β-like cells in the mouse pancreas by orthotopic transplantation of stem cell-derived β (SC-β) cells into the pancreas of neonatal mice. The engrafted β-like cells expressed β cell transcription factors and markers associated with functional maturity. Engrafted human cells recruited mouse endothelial cells, suggesting functional integration. Human insulin was detected in the blood circulation of transplanted mice for months after transplantation and increased upon glucose stimulation. In addition to β-like cells, human cells expressing markers for other endocrine pancreas cell types, acinar cells, and pancreatic ductal cells were identified in the pancreata of transplanted mice, indicating that this approach allows studying other human pancreatic cell types in the mouse pancreas. Our results demonstrate that orthotopic transplantation of human SC-β cells into neonatal mice is an experimental platform that allows the generation of mice with human pancreatic β-like cells in the endogenous niche.}, } @article {pmid29598825, year = {2018}, author = {Hernando-Rodríguez, B and Erinjeri, AP and Rodríguez-Palero, MJ and Millar, V and González-Hernández, S and Olmedo, M and Schulze, B and Baumeister, R and Muñoz, MJ and Askjaer, P and Artal-Sanz, M}, title = {Combined flow cytometry and high-throughput image analysis for the study of essential genes in Caenorhabditis elegans.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {36}, pmid = {29598825}, issn = {1741-7007}, support = {281691//European Research Council/International ; }, abstract = {BACKGROUND: Advances in automated image-based microscopy platforms coupled with high-throughput liquid workflows have facilitated the design of large-scale screens utilising multicellular model organisms such as Caenorhabditis elegans to identify genetic interactions, therapeutic drugs or disease modifiers. However, the analysis of essential genes has lagged behind because lethal or sterile mutations pose a bottleneck for high-throughput approaches, and a systematic way to analyse genetic interactions of essential genes in multicellular organisms has been lacking.

RESULTS: In C. elegans, non-conditional lethal mutations can be maintained in heterozygosity using chromosome balancers, commonly expressing green fluorescent protein (GFP) in the pharynx. However, gene expression or function is typically monitored by the use of fluorescent reporters marked with the same fluorophore, presenting a challenge to sort worm populations of interest, particularly at early larval stages. Here, we develop a sorting strategy capable of selecting homozygous mutants carrying a GFP stress reporter from GFP-balanced animals at the second larval stage. Because sorting is not completely error-free, we develop an automated high-throughput image analysis protocol that identifies and discards animals carrying the chromosome balancer. We demonstrate the experimental usefulness of combining sorting of homozygous lethal mutants and automated image analysis in a functional genomic RNA interference (RNAi) screen for genes that genetically interact with mitochondrial prohibitin (PHB). Lack of PHB results in embryonic lethality, while homozygous PHB deletion mutants develop into sterile adults due to maternal contribution and strongly induce the mitochondrial unfolded protein response (UPRmt). In a chromosome-wide RNAi screen for C. elegans genes having human orthologues, we uncover both known and new PHB genetic interactors affecting the UPRmt and growth.

CONCLUSIONS: The method presented here allows the study of balanced lethal mutations in a high-throughput manner. It can be easily adapted depending on the user's requirements and should serve as a useful resource for the C. elegans community for probing new biological aspects of essential nematode genes as well as the generation of more comprehensive genetic networks.}, } @article {pmid29597197, year = {2018}, author = {Mohr, RA and Chang, Y and Bhandiwad, AA and Forlano, PM and Sisneros, JA}, title = {Brain Activation Patterns in Response to Conspecific and Heterospecific Social Acoustic Signals in Female Plainfin Midshipman Fish, Porichthys notatus.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {1}, pages = {31-44}, pmid = {29597197}, issn = {1421-9743}, support = {SC2 DA034996/DA/NIDA NIH HHS/United States ; }, abstract = {While the peripheral auditory system of fish has been well studied, less is known about how the fish's brain and central auditory system process complex social acoustic signals. The plainfin midshipman fish, Porichthys notatus, has become a good species for investigating the neural basis of acoustic communication because the production and reception of acoustic signals is paramount for this species' reproductive success. Nesting males produce long-duration advertisement calls that females detect and localize among the noise in the intertidal zone to successfully find mates and spawn. How female midshipman are able to discriminate male advertisement calls from environmental noise and other acoustic stimuli is unknown. Using the immediate early gene product cFos as a marker for neural activity, we quantified neural activation of the ascending auditory pathway in female midshipman exposed to conspecific advertisement calls, heterospecific white seabass calls, or ambient environment noise. We hypothesized that auditory hindbrain nuclei would be activated by general acoustic stimuli (ambient noise and other biotic acoustic stimuli) whereas auditory neurons in the midbrain and forebrain would be selectively activated by conspecific advertisement calls. We show that neural activation in two regions of the auditory hindbrain, i.e., the rostral intermediate division of the descending octaval nucleus and the ventral division of the secondary octaval nucleus, did not differ via cFos immunoreactive (cFos-ir) activity when exposed to different acoustic stimuli. In contrast, female midshipman exposed to conspecific advertisement calls showed greater cFos-ir in the nucleus centralis of the midbrain torus semicircularis compared to fish exposed only to ambient noise. No difference in cFos-ir was observed in the torus semicircularis of animals exposed to conspecific versus heterospecific calls. However, cFos-ir was greater in two forebrain structures that receive auditory input, i.e., the central posterior nucleus of the thalamus and the anterior tuberal hypothalamus, when exposed to conspecific calls versus either ambient noise or heterospecific calls. Our results suggest that higher-order neurons in the female midshipman midbrain torus semicircularis, thalamic central posterior nucleus, and hypothalamic anterior tuberal nucleus may be necessary for the discrimination of complex social acoustic signals. Furthermore, neurons in the central posterior and anterior tuberal nuclei are differentially activated by exposure to conspecific versus other acoustic stimuli.}, } @article {pmid29597008, year = {2018}, author = {Liu, SV and Frédérich, B and Lavoué, S and Chang, J and Erdmann, MV and Mahardika, GN and Barber, PH}, title = {Buccal venom gland associates with increased of diversification rate in the fang blenny fish Meiacanthus (Blenniidae; Teleostei).}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {138-146}, doi = {10.1016/j.ympev.2018.03.027}, pmid = {29597008}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Biodiversity ; Organ Size ; Perciformes/*anatomy & histology/classification ; Phenotype ; Phylogeny ; Stochastic Processes ; Time Factors ; Venoms/*metabolism ; }, abstract = {At the macroevolutionary level, many mechanisms have been proposed to explain explosive species diversification. Among them morphological and/or physiological novelty is considered to have a great impact on the tempo and the mode of diversification. Meiacanthus is a genus of Blenniidae possessing a unique buccal venom gland at the base of an elongated canine tooth. This unusual trait has been hypothesized to aid escape from predation and thus potentially play an important role in their pattern of diversification. Here, we produce the first time-calibrated phylogeny of Blenniidae and we test the impact of two morphological novelties on their diversification, i.e. the presence of swim bladder and buccal venom gland, using various comparative methods. We found an increase in the tempo of lineage diversification at the root of the Meiacanthus clade, associated with the evolution of the buccal venom gland, but not the swim bladder. Neither morphological novelty was associated with the pattern of size disparification in blennies. Our results support the hypothesis that the buccal venom gland has contributed to the explosive diversification of Meiacanthus, but further analyses are needed to fully understand the factors sustaining this burst of speciation.}, } @article {pmid29596841, year = {2018}, author = {Vergara, HM and Ramirez, J and Rosing, T and Nave, C and Blandino, R and Saw, D and Saraf, P and Piexoto, G and Coombes, C and Adams, M and Domingo, CR}, title = {miR-206 is required for changes in cell adhesion that drive muscle cell morphogenesis in Xenopus laevis.}, journal = {Developmental biology}, volume = {438}, number = {2}, pages = {94-110}, doi = {10.1016/j.ydbio.2018.03.021}, pmid = {29596841}, issn = {1095-564X}, support = {R25 GM059298/GM/NIGMS NIH HHS/United States ; T34 GM008574/GM/NIGMS NIH HHS/United States ; P20 MD000544/MD/NIMHD NIH HHS/United States ; SC3 GM111118/GM/NIGMS NIH HHS/United States ; SC3 GM081165/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/genetics ; Animals ; Cell Adhesion/*genetics ; Cell Shape/genetics ; Dystroglycans/genetics ; Gene Expression Regulation, Developmental/genetics ; MicroRNAs/genetics/*metabolism ; Morphogenesis/genetics ; Muscle Cells/metabolism ; Muscle Development/genetics ; Muscles/metabolism ; Notochord/metabolism ; Sequence Homology, Nucleic Acid ; Somites/*metabolism/physiology ; Xenopus Proteins/genetics/metabolism ; Xenopus laevis/genetics ; }, abstract = {MicroRNAs (miRNAs) are highly conserved small non-coding RNA molecules that post-transcriptionally regulate gene expression in multicellular organisms. Within the set of muscle-specific miRNAs, miR-206 expression is largely restricted to skeletal muscle and is found exclusively within the bony fish lineage. Although many studies have implicated miR-206 in muscle maintenance and disease, its role in skeletal muscle development remains largely unknown. Here, we examine the role of miR-206 during Xenopus laevis somitogenesis. In Xenopus laevis, miR-206 expression coincides with the onset of somitogenesis. We show that both knockdown and over-expression of miR-206 result in abnormal somite formation affecting muscle cell rotation, attachment, and elongation. In particular, our data suggests that miR-206 regulates changes in cell adhesion that affect the ability of newly formed somites to adhere to the notochord as well as to the intersomitic boundaries. Additionally, we show that β-dystroglycan and F-actin expression levels are significantly reduced, suggesting that knockdown of miR-206 levels affects cellular mechanics necessary for cell shape changes and attachments that are required for proper muscle formation.}, } @article {pmid29596840, year = {2018}, author = {Magella, B and Mahoney, R and Adam, M and Potter, SS}, title = {Reduced Abd-B Hox function during kidney development results in lineage infidelity.}, journal = {Developmental biology}, volume = {438}, number = {2}, pages = {84-93}, pmid = {29596840}, issn = {1095-564X}, support = {P50 DK096418/DK/NIDDK NIH HHS/United States ; R01 DK099995/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Frameshift Mutation/genetics ; Gene Expression/genetics ; Gene Expression Regulation, Developmental/genetics ; Genes, Homeobox/*genetics/*physiology ; Homeodomain Proteins/*genetics/physiology ; Kidney/growth & development/metabolism ; Mice ; Morphogenesis/genetics ; Nephrons/growth & development/metabolism ; Organogenesis/genetics ; Stromal Cells/metabolism ; }, abstract = {Hox genes can function as key drivers of segment identity, with Hox mutations in Drosophila often resulting in dramatic homeotic transformations. In addition, however, they can serve other essential functions. In mammals, the study of Hox gene roles in development is complicated by the presence of four Hox clusters with a total of 39 genes showing extensive functional overlap. In this study, in order to better understand shared core Hox functions, we examined kidney development in mice with frameshift mutations of multiple Abd-B type Hox genes. The resulting phenotypes included dramatically reduced branching morphogenesis of the ureteric bud, premature depletion of nephron progenitors and abnormal development of the stromal compartment. Most unexpected, however, we also observed a cellular level lineage infidelity in nephron segments. Scattered cells within the proximal tubules, for example, expressed genes normally expressed only in collecting ducts. Multiple combinations of inappropriate nephron segment specific marker expression were found. In some cases, cells within a tubule showed incorrect identity, while in other cases cells showed ambiguous character, with simultaneous expression of genes associated with more than one nephron segment. These results give evidence that Hox genes have an overlapping core function at the cellular level in driving and/or maintaining correct differentiation decisions.}, } @article {pmid29596684, year = {2018}, author = {Jones, CT and Youssef, N and Susko, E and Bielawski, JP}, title = {Phenomenological Load on Model Parameters Can Lead to False Biological Conclusions.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1473-1488}, doi = {10.1093/molbev/msy049}, pmid = {29596684}, issn = {1537-1719}, abstract = {When a substitution model is fitted to an alignment using maximum likelihood, its parameters are adjusted to account for as much site-pattern variation as possible. A parameter might therefore absorb a substantial quantity of the total variance in an alignment (or more formally, bring about a substantial reduction in the deviance of the fitted model) even if the process it represents played no role in the generation of the data. When this occurs, we say that the parameter estimate carries phenomenological load (PL). Large PL in a parameter estimate is a concern because it not only invalidates its mechanistic interpretation (if it has one) but also increases the likelihood that it will be found to be statistically significant. The problem of PL was not identified in the past because most off-the-shelf substitution models make simplifying assumptions that preclude the generation of realistic levels of variation. In this study, we use the more realistic mutation-selection framework as the basis of a generating model formulated to produce data that mimic an alignment of mammalian mitochondrial DNA. We show that a parameter estimate can carry PL when 1) the substitution model is underspecified and 2) the parameter represents a process that is confounded with other processes represented in the data-generating model. We then provide a method that can be used to identify signal for the process that a given parameter represents despite the existence of PL.}, } @article {pmid29596640, year = {2018}, author = {Laurin-Lemay, S and Philippe, H and Rodrigue, N}, title = {Multiple Factors Confounding Phylogenetic Detection of Selection on Codon Usage.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1463-1472}, doi = {10.1093/molbev/msy047}, pmid = {29596640}, issn = {1537-1719}, abstract = {Detecting selection on codon usage (CU) is a difficult task, since CU can be shaped by both the mutational process and selective constraints operating at the DNA, RNA, and protein levels. Yang and Nielsen (2008) developed a test (which we call CUYN) for detecting selection on CU using two competing mutation-selection models of codon substitution. The null model assumes that CU is determined by the mutation bias alone, whereas the alternative model assumes that both mutation bias and/or selection act on CU. In applications on mammalian-scale alignments, the CUYN test detects selection on CU for numerous genes. This is surprising, given the small effective population size of mammals, and prompted us to use simulations to evaluate the robustness of the test to model violations. Simulations using a modest level of CpG hypermutability completely mislead the test, with 100% false positives. Surprisingly, a high level of false positives (56.1%) resulted simply from using the HKY mutation-level parameterization within the CUYN test on simulations conducted with a GTR mutation-level parameterization. Finally, by using a crude optimization procedure on a parameter controlling the CpG hypermutability rate, we find that this mutational property could explain a very large part of the observed mammalian CU. Altogether, our work emphasizes the need to evaluate the potential impact of model violations on statistical tests in the field of molecular phylogenetic analysis. The source code of the simulator and the mammalian genes used are available as a GitHub repository (https://github.com/Simonll/LikelihoodFreePhylogenetics.git).}, } @article {pmid29596635, year = {2018}, author = {Martinez, E and Siadous, FA and Bonazzi, M}, title = {Tiny architects: biogenesis of intracellular replicative niches by bacterial pathogens.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {4}, pages = {425-447}, doi = {10.1093/femsre/fuy013}, pmid = {29596635}, issn = {1574-6976}, mesh = {Bacteria/cytology ; *Bacterial Physiological Phenomena ; Drug Development ; Host-Pathogen Interactions/*physiology ; Membrane Transport Proteins/metabolism ; Protein Transport/physiology ; Signal Transduction/physiology ; }, abstract = {Co-evolution of bacterial pathogens with their hosts led to the emergence of a stunning variety of strategies aiming at the evasion of host defences, colonisation of host cells and tissues and, ultimately, the establishment of a successful infection. Pathogenic bacteria are typically classified as extracellular and intracellular; however, intracellular lifestyle comes in many different flavours: some microbes rapidly escape to the cytosol whereas other microbes remain within vacuolar compartments and harness membrane trafficking pathways to generate their host-derived, pathogen-specific replicative niche. Here we review the current knowledge on a variety of vacuolar lifestyles, the effector proteins used by bacteria as tools to take control of the host cell and the main membrane trafficking signalling pathways targeted by vacuolar pathogens as source of membranes and nutrients. Finally, we will also discuss how host cells have developed countermeasures to sense the biogenesis of the aberrant organelles harbouring bacteria. Understanding the dialogue between bacterial and eukaryotic proteins is the key to unravel the molecular mechanisms of infection and in turn, this may lead to the identification of new targets for the development of new antimicrobials.}, } @article {pmid29596620, year = {2018}, author = {Di Pippo, F and Di Gregorio, L and Congestri, R and Tandoi, V and Rossetti, S}, title = {Biofilm growth and control in cooling water industrial systems.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy044}, pmid = {29596620}, issn = {1574-6941}, abstract = {Matrix-embedded, surface-attached microbial communities, known as biofilms, profusely colonise industrial cooling water systems, where the availability of nutrients and organic matter favours rapid microbial proliferation and their adhesion to surfaces in the evaporative fill material, heat exchangers, water reservoir and cooling water sections and pipelines. The extensive growth of biofilms can promote micro-biofouling and microbially induced corrosion (MIC) as well as pose health problems associated with the presence of pathogens like Legionella pneumophila. This review examines critically biofilm occurrence in cooling water systems and the main factors potentially affecting biofilm growth, biodiversity and structure. A broad evaluation of the most relevant biofilm monitoring and control strategies currently used or potentially useful in cooling water systems is also provided.}, } @article {pmid29596003, year = {2018}, author = {Antonny, B and Bigay, J and Mesmin, B}, title = {The Oxysterol-Binding Protein Cycle: Burning Off PI(4)P to Transport Cholesterol.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {809-837}, doi = {10.1146/annurev-biochem-061516-044924}, pmid = {29596003}, issn = {1545-4509}, abstract = {To maintain an asymmetric distribution of ions across membranes, protein pumps displace ions against their concentration gradient by using chemical energy. Here, we describe a functionally analogous but topologically opposite process that applies to the lipid transfer protein (LTP) oxysterol-binding protein (OSBP). This multidomain protein exchanges cholesterol for the phosphoinositide phosphatidylinositol 4-phosphate [PI(4)P] between two apposed membranes. Because of the subsequent hydrolysis of PI(4)P, this counterexchange is irreversible and contributes to the establishment of a cholesterol gradient along organelles of the secretory pathway. The facts that some natural anti-cancer molecules block OSBP and that many viruses hijack the OSBP cycle for the formation of intracellular replication organelles highlight the importance and potency of OSBP-mediated lipid exchange. The architecture of some LTPs is similar to that of OSBP, suggesting that the principles of the OSBP cycle-burning PI(4)P for the vectorial transfer of another lipid-might be general.}, } @article {pmid29596002, year = {2018}, author = {Radkov, AD and Hsu, YP and Booher, G and VanNieuwenhze, MS}, title = {Imaging Bacterial Cell Wall Biosynthesis.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {991-1014}, pmid = {29596002}, issn = {1545-4509}, support = {R01 GM113172/GM/NIGMS NIH HHS/United States ; }, abstract = {Peptidoglycan is an essential component of the cell wall that protects bacteria from environmental stress. A carefully coordinated biosynthesis of peptidoglycan during cell elongation and division is required for cell viability. This biosynthesis involves sophisticated enzyme machineries that dynamically synthesize, remodel, and degrade peptidoglycan. However, when and where bacteria build peptidoglycan, and how this is coordinated with cell growth, have been long-standing questions in the field. The improvement of microscopy techniques has provided powerful approaches to study peptidoglycan biosynthesis with high spatiotemporal resolution. Recent development of molecular probes further accelerated the growth of the field, which has advanced our knowledge of peptidoglycan biosynthesis dynamics and mechanisms. Here, we review the technologies for imaging the bacterial cell wall and its biosynthesis activity. We focus on the applications of fluorescent d-amino acids, a newly developed type of probe, to visualize and study peptidoglycan synthesis and dynamics, and we provide direction for prospective research.}, } @article {pmid29595806, year = {2018}, author = {Klenerman, P and Ogg, G}, title = {Killer T cells show their kinder side.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {594-595}, doi = {10.1038/d41586-018-03510-z}, pmid = {29595806}, issn = {1476-4687}, mesh = {*Killer Cells, Natural ; *T-Lymphocytes, Cytotoxic ; }, } @article {pmid29595805, year = {2018}, author = {Poster, WR}, title = {Cybersecurity needs women.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {577-580}, doi = {10.1038/d41586-018-03327-w}, pmid = {29595805}, issn = {1476-4687}, mesh = {African Americans/statistics & numerical data ; Biometric Identification ; Computer Security/economics/history/*statistics & numerical data ; Female ; History, 20th Century ; History, 21st Century ; Humans ; Leadership ; Male ; Military Science ; Sex Factors ; Sexism/*prevention & control/*statistics & numerical data ; Stereotyped Behavior ; Women's Rights/history/statistics & numerical data/trends ; Workforce ; Workplace/statistics & numerical data ; }, } @article {pmid29595804, year = {2018}, author = {}, title = {Mushrooms: coming soon to a burger near you.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {560}, doi = {10.1038/d41586-018-03855-5}, pmid = {29595804}, issn = {1476-4687}, mesh = {*Agaricales/growth & development ; Agriculture/methods/trends ; Animals ; Carbon Footprint/*statistics & numerical data ; Cattle ; Conservation of Natural Resources/*methods/trends ; Efficiency, Organizational ; Environmental Policy ; Food Preferences ; Food Supply/*methods/*statistics & numerical data ; Forestry ; Humans ; Meat/*analysis ; Public Health/methods/trends ; Vegetables/growth & development ; }, } @article {pmid29595803, year = {2018}, author = {Gibney, E}, title = {First space mission dedicated to exoplanet atmospheres gets green light.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {571}, doi = {10.1038/d41586-018-03445-5}, pmid = {29595803}, issn = {1476-4687}, } @article {pmid29595802, year = {2018}, author = {Callaway, E}, title = {Divided by DNA: The uneasy relationship between archaeology and ancient genomics.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {573-576}, doi = {10.1038/d41586-018-03773-6}, pmid = {29595802}, issn = {1476-4687}, mesh = {*Archaeology ; DNA ; *Genomics ; History, Ancient ; }, } @article {pmid29595801, year = {2018}, author = {Hill, RZ and Bautista, DM}, title = {A trio of ion channels takes the heat.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {591-592}, doi = {10.1038/d41586-018-02663-1}, pmid = {29595801}, issn = {1476-4687}, mesh = {Guanine Nucleotide Exchange Factors ; *Hot Temperature ; *Ion Channels ; }, } @article {pmid29595800, year = {2018}, author = {Gleick, PH and Lewandowsky, S and Kelley, C}, title = {Critique of conflict and climate analysis is oversimplified.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {587}, doi = {10.1038/d41586-018-03794-1}, pmid = {29595800}, issn = {1476-4687}, mesh = {*Climate ; *Climate Change ; Conflict (Psychology) ; }, } @article {pmid29595799, year = {2018}, author = {Jalife, J}, title = {The tornadoes of sudden cardiac arrest.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {597-598}, doi = {10.1038/d41586-018-01950-1}, pmid = {29595799}, issn = {1476-4687}, mesh = {*Death, Sudden, Cardiac ; Heart Arrest ; Humans ; *Tornadoes ; }, } @article {pmid29595798, year = {2018}, author = {Zuber, MT}, title = {Oceans on Mars formed early.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {592-591}, doi = {10.1038/d41586-018-03415-x}, pmid = {29595798}, issn = {1476-4687}, mesh = {Exobiology ; *Extraterrestrial Environment ; *Mars ; Oceans and Seas ; Water/analysis ; }, } @article {pmid29595796, year = {2018}, author = {Fleming, N}, title = {Swedish science bounces back.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {S69-S70}, doi = {10.1038/d41586-018-03805-1}, pmid = {29595796}, issn = {1476-4687}, mesh = {Drug Industry/economics/organization & administration/trends ; Electronic Health Records ; Employment/statistics & numerical data/trends ; Entrepreneurship/trends ; Gross Domestic Product ; Science/economics/organization & administration/*trends ; Sweden ; Telemedicine ; Workforce ; }, } @article {pmid29595795, year = {2018}, author = {}, title = {Cambridge Analytica controversy must spur researchers to update data ethics.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {559-560}, doi = {10.1038/d41586-018-03856-4}, pmid = {29595795}, issn = {1476-4687}, mesh = {*Ethics Committees, Research ; *Research Personnel ; }, } @article {pmid29595793, year = {2018}, author = {Lowe, D}, title = {AI designs organic syntheses.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {592-593}, doi = {10.1038/d41586-018-03774-5}, pmid = {29595793}, issn = {1476-4687}, mesh = {*Chemistry Techniques, Synthetic ; }, } @article {pmid29595791, year = {2018}, author = {}, title = {Athlete brain bank, costly weather and science on social media.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {564-565}, doi = {10.1038/d41586-018-03772-7}, pmid = {29595791}, issn = {1476-4687}, } @article {pmid29595790, year = {2018}, author = {}, title = {Women feature only rarely as first or last authors in leading journals.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {691}, doi = {10.1038/d41586-018-03804-2}, pmid = {29595790}, issn = {1476-4687}, } @article {pmid29595789, year = {2018}, author = {}, title = {On the use and abuse of ancient DNA.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {559}, doi = {10.1038/d41586-018-03857-3}, pmid = {29595789}, issn = {1476-4687}, mesh = {*DNA, Ancient ; DNA, Mitochondrial ; *Fossils ; Sequence Analysis, DNA ; }, } @article {pmid29595788, year = {2018}, author = {Park, Y}, title = {Boost children's digital intelligence to protect against online threats.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {587}, doi = {10.1038/d41586-018-03797-y}, pmid = {29595788}, issn = {1476-4687}, mesh = {Child ; Humans ; *Intelligence ; }, } @article {pmid29595787, year = {2018}, author = {Zastrow, M}, title = {Four-in-one 3D printer paves way for custom-made robots and phones.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {569}, doi = {10.1038/d41586-018-03446-4}, pmid = {29595787}, issn = {1476-4687}, } @article {pmid29595786, year = {2018}, author = {Hsiang, S and Burke, M}, title = {Conclusion of conflict and climate analysis questioned.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {587}, doi = {10.1038/d41586-018-03798-x}, pmid = {29595786}, issn = {1476-4687}, mesh = {*Climate ; *Climate Change ; Conflict (Psychology) ; }, } @article {pmid29595784, year = {2018}, author = {Dance, A}, title = {Why laughter in the lab can help your science.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {689-691}, doi = {10.1038/d41586-018-03802-4}, pmid = {29595784}, issn = {1476-4687}, mesh = {Adaptation, Psychological ; Female ; Group Processes ; Humans ; *Job Satisfaction ; *Laboratories ; Laughter/*psychology ; Laughter Therapy ; Male ; Research/*standards ; Research Personnel/*psychology ; *Wit and Humor as Topic ; Workplace/*psychology ; }, } @article {pmid29595782, year = {2018}, author = {Reardon, S}, title = {Pioneering Alzheimer's study in Colombia zeroes in on enigmatic protein.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {567-568}, doi = {10.1038/d41586-018-03848-4}, pmid = {29595782}, issn = {1476-4687}, mesh = {Adolescent ; Adult ; Age of Onset ; Alzheimer Disease/diagnostic imaging/*drug therapy/*genetics/metabolism ; Antibodies, Monoclonal/therapeutic use ; *Biomedical Research ; Colombia ; Female ; Heterozygote ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy/*trends ; Plaque, Amyloid/drug therapy/genetics/metabolism ; *Positron-Emission Tomography/methods ; tau Proteins/analysis/*metabolism ; }, } @article {pmid29595781, year = {2018}, author = {Abbott, A}, title = {Reduced-calorie diet shows signs of slowing ageing in people.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {570-571}, doi = {10.1038/d41586-018-03431-x}, pmid = {29595781}, issn = {1476-4687}, mesh = {*Aging ; *Diet ; Energy Intake ; }, } @article {pmid29595780, year = {2018}, author = {Butler, CD and Kefford, BJ}, title = {Climate change as a contributor to human conflict.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {587}, doi = {10.1038/d41586-018-03795-0}, pmid = {29595780}, issn = {1476-4687}, mesh = {*Climate Change ; Humans ; }, } @article {pmid29595779, year = {2018}, author = {}, title = {More than one-third of graduate students report being depressed.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {691}, doi = {10.1038/d41586-018-03803-3}, pmid = {29595779}, issn = {1476-4687}, } @article {pmid29595778, year = {2018}, author = {Koehler, N and Baiker, A and Busch, U}, title = {Details matter for contaminants in genetic-engineering kits.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {587}, doi = {10.1038/d41586-018-03796-z}, pmid = {29595778}, issn = {1476-4687}, mesh = {*Genetic Engineering ; *Reagent Kits, Diagnostic ; }, } @article {pmid29595777, year = {2018}, author = {Rétaux, S}, title = {The healthy diabetic cavefish conundrum.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {595-597}, doi = {10.1038/d41586-018-03242-0}, pmid = {29595777}, issn = {1476-4687}, mesh = {Biological Evolution ; Diabetes Mellitus ; *Eye ; Fishes/genetics ; *Gene Expression Regulation, Developmental ; Humans ; }, } @article {pmid29595776, year = {2018}, author = {Tollefson, J}, title = {Ocean scientists work to forecast huge plankton blooms in Arabian Sea.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {569-570}, doi = {10.1038/d41586-018-03698-0}, pmid = {29595776}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/growth & development ; Dinoflagellida/*growth & development ; *Forecasting ; Models, Biological ; *Oceans and Seas ; Plankton/*growth & development ; Seawater/*microbiology ; }, } @article {pmid29595775, year = {2018}, author = {More, B}, title = {Drug executives should take a Hippocratic oath.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {561}, doi = {10.1038/d41586-018-03230-4}, pmid = {29595775}, issn = {1476-4687}, mesh = {Consumer Behavior/economics ; Drug Industry/*economics/*organization & administration ; Hepatitis C/drug therapy ; *Hippocratic Oath ; Humans ; Patents as Topic ; *Patient Satisfaction/economics ; Sofosbuvir/economics/therapeutic use ; *Trust ; Workforce ; }, } @article {pmid29595774, year = {2018}, author = {Fleming, N}, title = {Q&A: Elina Berglund on moving from physics to fertility.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {S71}, doi = {10.1038/d41586-018-03806-0}, pmid = {29595774}, issn = {1476-4687}, } @article {pmid29595773, year = {2018}, author = {Fleming, N}, title = {How a bridge brought science closer together.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {S72-S73}, doi = {10.1038/d41586-018-03807-z}, pmid = {29595773}, issn = {1476-4687}, mesh = {Biological Science Disciplines/*organization & administration/standards ; Biomedical Research/organization & administration/standards ; Denmark ; Drug Industry/organization & administration ; Sweden ; *Travel ; Workforce ; }, } @article {pmid29595772, year = {2018}, author = {Morello, L and Guglielmi, G}, title = {US science agencies set to win big in budget deal.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {572}, doi = {10.1038/d41586-018-03700-9}, pmid = {29595772}, issn = {1476-4687}, mesh = {Budgets/*legislation & jurisprudence ; *Federal Government ; National Institutes of Health (U.S.)/*economics/*legislation & jurisprudence ; Research Support as Topic/economics/legislation & jurisprudence ; United States ; United States Environmental Protection Agency/economics/legislation & jurisprudence ; }, } @article {pmid29595771, year = {2018}, author = {Wilkinson, R}, title = {Wing origami.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {594}, doi = {10.1038/d41586-018-03775-4}, pmid = {29595771}, issn = {1476-4687}, } @article {pmid29595770, year = {2018}, author = {van Dokkum, P and Danieli, S and Cohen, Y and Merritt, A and Romanowsky, AJ and Abraham, R and Brodie, J and Conroy, C and Lokhorst, D and Mowla, L and O'Sullivan, E and Zhang, J}, title = {A galaxy lacking dark matter.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {629-632}, pmid = {29595770}, issn = {1476-4687}, abstract = {Studies of galaxy surveys in the context of the cold dark matter paradigm have shown that the mass of the dark matter halo and the total stellar mass are coupled through a function that varies smoothly with mass. Their average ratio Mhalo/Mstars has a minimum of about 30 for galaxies with stellar masses near that of the Milky Way (approximately 5 × 1010 solar masses) and increases both towards lower masses and towards higher masses. The scatter in this relation is not well known; it is generally thought to be less than a factor of two for massive galaxies but much larger for dwarf galaxies. Here we report the radial velocities of ten luminous globular-cluster-like objects in the ultra-diffuse galaxy NGC1052-DF2, which has a stellar mass of approximately 2 × 108 solar masses. We infer that its velocity dispersion is less than 10.5 kilometres per second with 90 per cent confidence, and we determine from this that its total mass within a radius of 7.6 kiloparsecs is less than 3.4 × 108 solar masses. This implies that the ratio Mhalo/Mstars is of order unity (and consistent with zero), a factor of at least 400 lower than expected. NGC1052-DF2 demonstrates that dark matter is not always coupled with baryonic matter on galactic scales.}, } @article {pmid29595769, year = {2018}, author = {Ghalambor, CK and Hoke, KL and Ruell, EW and Fischer, EK and Reznick, DN and Hughes, KA}, title = {Erratum: Non-adaptive plasticity potentiates rapid adaptive evolution of gene expression in nature.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {688}, pmid = {29595769}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature15256.}, } @article {pmid29595768, year = {2018}, author = {van Gestel, J and Weissing, FJ}, title = {Is plasticity caused by single genes?.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {E19-E20}, pmid = {29595768}, issn = {1476-4687}, } @article {pmid29595767, year = {2018}, author = {Segler, MHS and Preuss, M and Waller, MP}, title = {Planning chemical syntheses with deep neural networks and symbolic AI.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {604-610}, pmid = {29595767}, issn = {1476-4687}, mesh = {*Artificial Intelligence ; Chemistry Techniques, Synthetic/*methods ; Chemistry, Organic/methods ; Monte Carlo Method ; *Neural Networks (Computer) ; }, abstract = {To plan the syntheses of small organic molecules, chemists use retrosynthesis, a problem-solving technique in which target molecules are recursively transformed into increasingly simpler precursors. Computer-aided retrosynthesis would be a valuable tool but at present it is slow and provides results of unsatisfactory quality. Here we use Monte Carlo tree search and symbolic artificial intelligence (AI) to discover retrosynthetic routes. We combined Monte Carlo tree search with an expansion policy network that guides the search, and a filter network to pre-select the most promising retrosynthetic steps. These deep neural networks were trained on essentially all reactions ever published in organic chemistry. Our system solves for almost twice as many molecules, thirty times faster than the traditional computer-aided search method, which is based on extracted rules and hand-designed heuristics. In a double-blind AB test, chemists on average considered our computer-generated routes to be equivalent to reported literature routes.}, } @article {pmid29595766, year = {2018}, author = {Ghalambor, CK and Hoke, KL and Ruell, EW and Fischer, EK and Reznick, DN and Hughes, KA}, title = {Ghalambor et al. reply.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {E23}, pmid = {29595766}, issn = {1476-4687}, } @article {pmid29595765, year = {2018}, author = {Mallard, F and Jakšić, AM and Schlötterer, C}, title = {Contesting the evidence for non-adaptive plasticity.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {E21-E22}, pmid = {29595765}, issn = {1476-4687}, } @article {pmid29595416, year = {2018}, author = {Pavan, ME and Pavan, EE and Glaeser, SP and Etchebehere, C and Kämpfer, P and Pettinari, MJ and López, NI}, title = {Proposal for a new classification of a deep branching bacterial phylogenetic lineage: transfer of Coprothermobacter proteolyticus and Coprothermobacter platensis to Coprothermobacteraceae fam. nov., within Coprothermobacterales ord. nov., Coprothermobacteria classis nov. and Coprothermobacterota phyl. nov. and emended description of the family Thermodesulfobiaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1627-1632}, doi = {10.1099/ijsem.0.002720}, pmid = {29595416}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Firmicutes/*classification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The genus Coprothermobacter (initially named Thermobacteroides) is currently placed within the phylum Firmicutes. Early 16S rRNA gene based phylogenetic studies pointed out the great differences between Coprothermobacter and other members of the Firmicutes, revealing that it constitutes a new deep branching lineage. Over the years, several studies based on 16S rRNA gene and whole genome sequences have indicated that Coprothermobacter is very distant phylogenetically to all other bacteria, supporting its placement in a distinct deeply rooted novel phylum. In view of this, we propose its allocation to the new family Coprothermobacteraceae within the novel order Coprothermobacterales, the new class Coprothermobacteria, and the new phylum Coprothermobacterota, and an emended description of the family Thermodesulfobiaceae.}, } @article {pmid29595413, year = {2018}, author = {Kimura, N and Watanabe, T and Suenaga, H and Fujihara, H and Futagami, T and Goto, M and Hanada, S and Hirose, J}, title = {Pseudomonas furukawaii sp. nov., a polychlorinated biphenyl-degrading bacterium isolated from biphenyl-contaminated soil in Japan.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1429-1435}, doi = {10.1099/ijsem.0.002670}, pmid = {29595413}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Environmental Pollution ; Fatty Acids/chemistry ; Japan ; Nucleic Acid Hybridization ; *Phylogeny ; Polychlorinated Biphenyls/*metabolism ; Pseudomonas/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {Strain KF707T was isolated from a biphenyl-contaminated site in Kitakyushu, Japan. Analysis of 16S rRNA gene sequences, retrieved from the whole-genome sequence, revealed that the isolate was closely related to members of the genus Pseudomonas, sharing the highest sequence similarities with Pseudomonas balearica strain SP1402T (DSM 6083) (97.8 %). The DNA G+C chromosome and plasmid content of strain KF707T were 65.5 and 60.5 mol%. The major cellular fatty acids were iso-C15 : 0 and C16 : 1ω7c/C16 : 1ω6c. Polyphasic analysis indicated that strain KF707T represents a novel species of the genus Pseudomonas, for which the name Pseudomonas furukawaii sp. nov. is proposed. The type strain is KF707T (=DSM 10086T=NBRC 110670T).}, } @article {pmid29594426, year = {2018}, author = {Skoblikow, NE and Zimin, AA}, title = {Mineral Grains, Dimples, and Hot Volcanic Organic Streams: Dynamic Geological Backstage of Macromolecular Evolution.}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {172-183}, pmid = {29594426}, issn = {1432-1432}, abstract = {The hypothesis of hot volcanic organic stream as the most probable and geologically plausible environment for abiogenic polycondensation is proposed. The primary synthesis of organic compounds is considered as result of an explosive volcanic (perhaps, meteorite-induced) eruption. The eruption was accompanied by a shock wave propagating in the primeval atmosphere and resulting in the formation of hot cloud of simple organic compounds-aldehydes, alcohols, amines, amino alcohols, nitriles, and amino acids-products, which are usually obtained under the artificial conditions in the spark-discharge experiments. The subsequent cooling of the organic cloud resulted in a gradual condensation and a serial precipitation of organic compounds (in order of decreasing boiling point values) into the liquid phase forming a hot, viscous and muddy organic stream (named "lithorheos"). That stream-even if the time of its existence was short-is considered here as a geologically plausible environment for abiogenic polycondensation. The substances successively prevailing in such a stream were cyanamide, acetamide, formamide, glycolonitrile, acetonitrile. An important role was played by mineral (especially, phosphate-containing) grains (named "lithosomes"), whose surface was modified with heterocyclic nitrogen compounds synthesized in the course of eruption. When such grains got into hot organic streams, their surface catalytic centers (named "lithozymes") played a decisive role in the emergence, facilitation and maintenance of prebiotic reactions and key processes characteristic of living systems. Owing to its cascade structure, the stream was a factor underlying the formation of mineral-polymeric aggregates (named "lithocytes") in the small natural streambed cavities (dimples)-as well as a factor of their further spread within larger geological locations which played a role of chemo-ecological niches. All three main stages of prebiotic evolution (primary organic synthesis, polycondensation, and formation of proto-cellular structures) are combined within a common dynamic geological process. We suppose macromolecular evolution had an extremely fast, "flash" start: the period from volcanic eruption to formation of lithocyte "populations" took not million years but just several tens of minutes. The scenario proposed can be verified experimentally with a three-module setup working with principles of dynamic (flow) chemistry in its core element.}, } @article {pmid29594405, year = {2018}, author = {da Silva-Marques, RP and Zervoudakis, JT and Nakazato, L and da Silva Cabral, L and Hatamoto-Zervoudakis, LK and da Silva, MIL and do Nascimento Matos, NB and Pitchenin, LC}, title = {Quantitative qPCR Analysis of Ruminal Microorganisms in Beef Cattle Grazing in Pastures in the Rainy Season and Supplemented with Different Protein Levels.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1025-1032}, pmid = {29594405}, issn = {1432-0991}, mesh = {Animal Feed/*analysis ; Animal Nutritional Physiological Phenomena ; Animals ; Butyrivibrio fibrisolvens/genetics/*isolation & purification ; Cattle ; Dietary Proteins/*administration & dosage ; Dietary Supplements/*analysis ; Fibrobacter/classification/genetics/*isolation & purification ; Male ; RNA, Ribosomal, 16S/genetics ; Rain ; Rumen/*microbiology ; Ruminococcus/classification/genetics/*isolation & purification ; Seasons ; Tropical Climate ; }, abstract = {We tested the hypothesis that supplementation with three protein levels improves fermentation parameters without changing the rumen microbial population of grazing beef cattle in the rainy season. Four rumen-cannulated Nellore bulls (432 ± 21 kg of body weight) were used in a 4 × 4 Latin square design with four supplements and four experimental periods of 21 days each. The treatments were mineral supplement (ad libitum) and supplements with low, medium (MPS), and high protein supplement (HPS), supplying 106, 408, and 601 g/day of CP, respectively. The abundance of each target taxon was calculated as a fraction of the total 16S rRNA gene copies in the samples, using taxon-specific and domain bacteria primers. Supplemented animals showed lower (P < 0.05) proportions of Ruminococcus flavefaciens and greater (P < 0.05) proportions of Ruminococcus albus and Butyrivibrio fibrisolvens than animals that received only the mineral supplement. The HPS supplement resulted in higher (P < 0.05) proportions of Fibrobacter succinogenes, R. flavefaciens, and B. fibrisolvens and lower (P < 0.05) proportions of R. albus than the MPS supplement. Based on our results, high protein supplementation improves the ruminal conditions and facilitates the growth of cellulolytic bacteria in the rumen of bulls on pastures during the rainy season.}, } @article {pmid29594404, year = {2018}, author = {de Meij, TGJ and Budding, AE}, title = {Single Sampling Versus Multiple Testing Strategy to Assess Gut Microbiota Composition: Does It Matter?.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1487-z}, pmid = {29594404}, issn = {1432-0991}, } @article {pmid29594403, year = {2018}, author = {Zhang, Y and Ge, Q and Cao, Q and Cui, H and Hu, P and Yu, X and Ye, Z}, title = {Cloning and Characterization of Two MAPK Genes UeKpp2 and UeKpp6 in Ustilago esculenta.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1016-1024}, pmid = {29594403}, issn = {1432-0991}, support = {LQ15C140003//Natural Science Foundation of Zhejiang Province/ ; 31600634//National Natural Science Foundation of China/ ; 31470785//National Natural Science Foundation of China/ ; }, mesh = {Fungal Proteins/*genetics/*metabolism ; Gene Expression Regulation, Fungal/genetics ; High Mobility Group Proteins/*metabolism ; Mitogen-Activated Protein Kinase Kinases/*metabolism ; Mitogen-Activated Protein Kinases/*genetics/*metabolism ; Poaceae/microbiology ; Ustilago/*genetics ; }, abstract = {Ustilago esculenta, resembling a fungal endophyte in Zizania latifolia, inhibits the host plant flowering and induces the host stems to swell and form edible galls. It is well believed that when and how the fungus infects and proliferates in the host plants during the host development is of importance in the edible gall formation. Mitogen-activated protein kinases (MAPKs) have been found to play an important role in sensing environment cues and regulating infection. Two MAPK genes UeKpp2 and UeKpp6 from U. esculenta were cloned and suggested to be involved in the Fus3/Kss1 pathway by a phylogenetic analysis with the neighbor-joining method. Quantitative RT-PCR (qRT-PCR) analyses indicated that expression of UeKpp2 and UeKpp6 were induced during mating and infection processes, and their expression patterns displayed differentially under different carbon and nitrogen sources. In addition, subcellular localization of UeKpp2 or UeKpp6 fused with the reporter green fluoresce protein was observed by confocal laser scanning microscope, and yeast two-hybrid assays were carried out. Results showed that both UeKpp2 and UeKpp6 were located in cytoplasm and interacted with UePrf1, indicating their involvement in hyphal growth and host-pathogen regulation. Only UeKpp2 but not UeKpp6 interacted with the upstream MAPK kinase UeFuz7, implying an additional MAPK pathway, in which UeKpp6 involved, existed.}, } @article {pmid29593244, year = {2018}, author = {Treves, A and Artelle, KA and Darimont, CT and Lynn, WS and Paquet, P and Santiago-Ávila, FJ and Shaw, R and Wood, MC}, title = {Author Correction: Intergenerational equity can help to prevent climate change and extinction.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {910}, doi = {10.1038/s41559-018-0512-8}, pmid = {29593244}, issn = {2397-334X}, abstract = {The original Article mistakenly coded the constitutional rights of Australia as containing a governmental duty to protect the environment (blue in the figures); this has been corrected to containing no explicit mention of environmental protection (orange in the figures). The original Article also neglected to code the constitutional rights of the Cayman Islands (no data; yellow in the figures); this has been corrected to containing a governmental duty to protect the environment (blue in the figures).Although no inferences changed as a result of these errors, many values changed slightly and have been corrected. The proportion of the world's nations having constitutional rights to a healthy environment changed from 75% to 74%. The proportions of nations in different categories given in the Fig. 1 caption all changed except purple countries (3.1%): green countries changed from 47.2% to 46.9%; blue countries changed from 24.4% to 24.2%; and orange countries changed from 25.3% to 25.8%. The proportion of the global atmospheric CO2 emitted by the 144 nations changed from 72.6% to 74.4%; the proportion of the world's population represented by the 144 nations changed from 84.9% to 85%. The values of annual average CO2 emissions for blue countries changed from 363,000 Gg to 353,000 Gg and for orange countries from 195,000 Gg to 201,000 Gg. The proportion of threatened mammals endemic to a single country represented by the 144 countries changed from 91% to 84%. Figures 1-3 have been updated to show the correct values and map colours and the Supplementary Information has been updated to give the correct country codes.}, } @article {pmid29593243, year = {2018}, author = {O'Bryan, CJ and Braczkowski, AR and Beyer, HL and Carter, NH and Watson, JEM and McDonald-Madden, E}, title = {Author Correction: The contribution of predators and scavengers to human well-being.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {911}, doi = {10.1038/s41559-018-0527-1}, pmid = {29593243}, issn = {2397-334X}, abstract = {In the version of this Review originally published, there were a number of errors that the authors wish to correct.}, } @article {pmid29592955, year = {2018}, author = {Adler, DH and Wisse, LEM and Ittyerah, R and Pluta, JB and Ding, SL and Xie, L and Wang, J and Kadivar, S and Robinson, JL and Schuck, T and Trojanowski, JQ and Grossman, M and Detre, JA and Elliott, MA and Toledo, JB and Liu, W and Pickup, S and Miller, MI and Das, SR and Wolk, DA and Yushkevich, PA}, title = {Characterizing the human hippocampus in aging and Alzheimer's disease using a computational atlas derived from ex vivo MRI and histology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4252-4257}, pmid = {29592955}, issn = {1091-6490}, support = {P30 AG010124/AG/NIA NIH HHS/United States ; P01 AG017586/AG/NIA NIH HHS/United States ; R01 AG038490/AG/NIA NIH HHS/United States ; R01 EB017255/EB/NIBIB NIH HHS/United States ; R01 AG037376/AG/NIA NIH HHS/United States ; P41 EB015893/EB/NIBIB NIH HHS/United States ; R01 AG056014/AG/NIA NIH HHS/United States ; R03 EB016923/EB/NIBIB NIH HHS/United States ; P30 NS045839/NS/NINDS NIH HHS/United States ; }, mesh = {Aged ; Aging/*pathology ; Alzheimer Disease/*pathology ; *Atlases as Topic ; Atrophy ; Dentate Gyrus/pathology ; Hippocampus/*pathology ; Humans ; Imaging, Three-Dimensional ; *Magnetic Resonance Imaging ; *Neuroimaging ; Organ Size ; }, abstract = {Although the hippocampus is one of the most studied structures in the human brain, limited quantitative data exist on its 3D organization, anatomical variability, and effects of disease on its subregions. Histological studies provide restricted reference information due to their 2D nature. In this paper, high-resolution (∼200 × 200 × 200 μm3) ex vivo MRI scans of 31 human hippocampal specimens are combined using a groupwise diffeomorphic registration approach into a 3D probabilistic atlas that captures average anatomy and anatomic variability of hippocampal subfields. Serial histological imaging in 9 of the 31 specimens was used to label hippocampal subfields in the atlas based on cytoarchitecture. Specimens were obtained from autopsies in patients with a clinical diagnosis of Alzheimer's disease (AD; 9 subjects, 13 hemispheres), of other dementia (nine subjects, nine hemispheres), and in subjects without dementia (seven subjects, nine hemispheres), and morphometric analysis was performed in atlas space to measure effects of age and AD on hippocampal subfields. Disproportional involvement of the cornu ammonis (CA) 1 subfield and stratum radiatum lacunosum moleculare was found in AD, with lesser involvement of the dentate gyrus and CA2/3 subfields. An association with age was found for the dentate gyrus and, to a lesser extent, for CA1. Three-dimensional patterns of variability and disease and aging effects discovered via the ex vivo hippocampus atlas provide information highly relevant to the active field of in vivo hippocampal subfield imaging.}, } @article {pmid29592954, year = {2018}, author = {Arp, J and Götze, S and Mukherji, R and Mattern, DJ and García-Altares, M and Klapper, M and Brock, DA and Brakhage, AA and Strassmann, JE and Queller, DC and Bardl, B and Willing, K and Peschel, G and Stallforth, P}, title = {Synergistic activity of cosecreted natural products from amoebae-associated bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3758-3763}, pmid = {29592954}, issn = {1091-6490}, mesh = {4-Butyrolactone/analogs & derivatives/physiology ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics/metabolism ; Biological Products/*pharmacology ; Dictyostelium/*physiology ; *Drug Synergism ; Genome, Bacterial ; Methicillin-Resistant Staphylococcus aureus/drug effects ; Mupirocin/*pharmacology ; Pseudomonas/*metabolism ; Quorum Sensing/*physiology ; Staphylococcal Infections/*drug therapy/metabolism/microbiology ; }, abstract = {Investigating microbial interactions from an ecological perspective is a particularly fruitful approach to unveil both new chemistry and bioactivity. Microbial predator-prey interactions in particular rely on natural products as signal or defense molecules. In this context, we identified a grazing-resistant Pseudomonas strain, isolated from the bacterivorous amoeba Dictyostelium discoideum. Genome analysis of this bacterium revealed the presence of two biosynthetic gene clusters that were found adjacent to each other on a contiguous stretch of the bacterial genome. Although one cluster codes for the polyketide synthase producing the known antibiotic mupirocin, the other cluster encodes a nonribosomal peptide synthetase leading to the unreported cyclic lipopeptide jessenipeptin. We describe its complete structure elucidation, as well as its synergistic activity against methicillin-resistant Staphylococcus aureus, when in combination with mupirocin. Both biosynthetic gene clusters are regulated by quorum-sensing systems, with 3-oxo-decanoyl homoserine lactone (3-oxo-C10-AHL) and hexanoyl homoserine lactone (C6-AHL) being the respective signal molecules. This study highlights the regulation, richness, and complex interplay of bacterial natural products that emerge in the context of microbial competition.}, } @article {pmid29592953, year = {2018}, author = {Zhao, L and Huang, S and Mei, S and Yang, Z and Xu, L and Zhou, N and Yang, Q and Shen, Q and Wang, W and Le, X and Lau, WB and Lau, B and Wang, X and Yi, T and Zhao, X and Wei, Y and Warner, M and Gustafsson, JÅ and Zhou, S}, title = {Pharmacological activation of estrogen receptor beta augments innate immunity to suppress cancer metastasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3673-E3681}, pmid = {29592953}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*pharmacology/therapeutic use ; Apoptosis/drug effects ; Benzopyrans/*pharmacology/therapeutic use ; Cell Line, Tumor ; Drug Screening Assays, Antitumor ; Estrogen Receptor Modulators/*pharmacology/therapeutic use ; Estrogen Receptor beta/*agonists ; Estrogens ; Female ; Immunity, Innate/*drug effects ; Interleukin-1beta/deficiency/genetics ; Lung Neoplasms/immunology/*secondary/therapy ; Mammary Neoplasms, Experimental/immunology/*pathology/therapy ; Melanoma, Experimental/immunology/*secondary/therapy ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms, Hormone-Dependent/immunology/secondary/therapy ; Neutrophil Infiltration/*drug effects ; Neutrophils/drug effects/immunology ; Specific Pathogen-Free Organisms ; Triple Negative Breast Neoplasms/*therapy ; Tumor Microenvironment/drug effects/immunology ; }, abstract = {Metastases constitute the greatest causes of deaths from cancer. However, no effective therapeutic options currently exist for cancer patients with metastasis. Estrogen receptor β (ERβ), as a member of the nuclear receptor superfamily, shows potent tumor-suppressive activities in many cancers. To investigate whether modulation of ERβ could serve as a therapeutic strategy for cancer metastasis, we examined whether the selective ERβ agonist LY500307 could suppress lung metastasis of triple-negative breast cancer (TNBC) and melanoma. Mechanistically, while we observed that LY500307 potently induced cell death of cancer cells metastasized to lung in vivo, it does not mediate apoptosis of cancer cells in vitro, indicating that the cell death-inducing effects of LY500307 might be mediated by the tumor microenvironment. Pathological examination combined with flow cytometry assays indicated that LY500307 treatment induced significant infiltration of neutrophils in the metastatic niche. Functional experiments demonstrated that LY500307-treated cancer cells show chemotactic effects for neutrophils and that in vivo neutrophil depletion by Ly6G antibody administration could reverse the effects of LY500307-mediated metastasis suppression. RNA sequencing analysis showed that LY500307 could induce up-regulation of IL-1β in TNBC and melanoma cells, which further triggered antitumor neutrophil chemotaxis. However, the therapeutic effects of LY500307 treatment for suppression of lung metastasis was attenuated in IL1B-/- murine models, due to failure to induce antitumor neutrophil infiltration in the metastatic niche. Collectively, our study demonstrated that pharmacological activation of ERβ could augment innate immunity to suppress cancer metastatic colonization to lung, thus providing alternative therapeutic options for cancer patients with metastasis.}, } @article {pmid29592952, year = {2018}, author = {Pyron, RA}, title = {Global amphibian declines have winners and losers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3739-3741}, pmid = {29592952}, issn = {1091-6490}, mesh = {*Amphibians ; Animals ; *Competitive Behavior ; }, } @article {pmid29592951, year = {2018}, author = {Licznerski, P and Jonas, EA}, title = {BDNF signaling: Harnessing stress to battle mood disorder.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3742-3744}, pmid = {29592951}, issn = {1091-6490}, mesh = {Bipolar Disorder ; *Brain-Derived Neurotrophic Factor ; Depressive Disorder, Major ; Humans ; *Mood Disorders ; Signal Transduction ; }, } @article {pmid29592815, year = {2018}, author = {Atey, TM and Teklay, T and Asgedom, SW and Mezgebe, HB and Teklay, G and Kahssay, M}, title = {Treatment optimization of angiotensin converting enzyme inhibitors and associated factors in Ayder Comprehensive Specialized Hospital: a cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {209}, pmid = {29592815}, issn = {1756-0500}, mesh = {Adult ; Aged ; Angiotensin-Converting Enzyme Inhibitors/*therapeutic use ; Cross-Sectional Studies ; Enalapril/*therapeutic use ; Female ; Heart Failure/*drug therapy ; *Hospitals, Special ; Humans ; Kaplan-Meier Estimate ; Male ; Middle Aged ; Retrospective Studies ; Treatment Outcome ; Young Adult ; }, abstract = {BACKGROUND: Angiotensin-converting enzyme inhibitors have morbidity and mortality benefits in heart failure. Failure to optimize treatment using these medications increases hospitalizations, worsens signs and symptoms of heart failure, and reduces the overall treatment outcome. Therefore, the main purpose of this study was to assess the practice of treatment optimization of these medications and associated factors.

RESULTS: A hospital-based cross-sectional study was conducted on 61 ambulatory heart failure patients, recruited using a convenience sampling technique, from February 25 to May 24, 2016 at the cardiology clinic of Ayder Comprehensive Specialized Hospital. Descriptive, inferential and Kaplan-Meier 'tolerability' analyses were employed. All patients were taking only enalapril as part of their angiotensin converting enzyme inhibitor treatment. According to the 2013 American College of Cardiology/American Heart Association guideline, about fourth-fifth (80.3%) of the patients were tolerating to the hypotensive effect of enalapril. The dose of enalapril was timely titrated (every 2-4 weeks) and was optimized for only 11.5 and 27.8% of the patients, respectively. Considering the tolerance, timely titration, and dose optimization, only 3.3% of the overall enalapril treatment was optimized. Multivariate regression results showed that the odds of having timely titration of enalapril for patients who were taking enalapril and calcium channel blockers were almost 20 times [adjusted odds ratio (AOR) = 21.68, 95% confidence interval (CI) 1.23-383.16, p < 0.036] more compared to patients who were taking enalapril and β-blockers. A Log Rank Chi Square result showed a 19.42 magnitude of better toleration of enalapril (p < 0.001) for patients who were taking enalapril for more than 1 year compared to less than a year.

CONCLUSION: This study provides a platform for assessment of the treatment optimization practice of enalapril, which remains the pressing priority and found to be poor in the ambulatory setting, despite a better tolerability to the hypotensive effect of enalapril. We call for greater momentum of efforts by health care providers in optimizing the treatment practice to benchmark with other optimization practices.}, } @article {pmid29592808, year = {2018}, author = {Barlow, LD and Nývltová, E and Aguilar, M and Tachezy, J and Dacks, JB}, title = {Correction to: A sophisticated, differentiated Golgi in the ancestor of eukaryotes.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {35}, pmid = {29592808}, issn = {1741-7007}, abstract = {Upon publication of the original article, Barlow et al. [1], the authors noticed that Fig. 4b contained an inaccuracy when additional data is taken into account. We inferred a loss of GRASP in the common ancestor of cryptophytes and archaeplastids, based on the absence of identified homologues in the data from taxa that we analyzed, which include Cyanidioschyzon merolae as the single representative of red algae.}, } @article {pmid29592799, year = {2018}, author = {Quéméré, E and Gaillard, JM and Galan, M and Vanpé, C and David, I and Pellerin, M and Kjellander, P and Hewison, AJM and Pemberton, JM}, title = {Between-population differences in the genetic and maternal components of body mass in roe deer.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {39}, pmid = {29592799}, issn = {1471-2148}, support = {ANR-12-PDOC-0017-01//Agence Nationale de la Recherche/International ; }, mesh = {Animals ; Body Weight/*genetics ; Deer/*anatomy & histology/*genetics ; Demography ; Ecosystem ; Europe ; Female ; Genetic Variation ; *Genetics, Population ; Male ; Reproduction/physiology ; Seasons ; }, abstract = {BACKGROUND: Understanding the genetic and environmental mechanisms governing variation in morphology or phenology in wild populations is currently an important challenge. While there is a general consensus that selection is stronger under stressful conditions, it remains unclear whether the evolutionary potential of traits should increase or decrease with increasingly stressful conditions. Here, we investigate how contrasting environmental conditions during growth may affect the maternal and genetic components of body mass in roe deer, the most abundant and widespread wild ungulate in Western Europe. Body mass is a key life history trait that strongly influences both survival and reproductive performance in large herbivores. We used pedigrees and animal models to determine the variance components of juvenile and adult winter body mass in two populations experiencing contrasting early-life conditions.

RESULTS: Our analyses showed that roe deer at Chizé, where habitat was poor and unpredictable, exhibited very low genetic variance in juvenile body mass. Instead, variance in mass was mainly driven by among-cohort differences in early-life conditions and maternal environment. In contrast, roe deer at Bogesund, where resource availability during the critical period of fawn rearing was higher, displayed a substantial level of genetic variance in body mass. We discuss the potential role of past demography and viability selection on fawn body mass on the erosion of genetic variance in the poor habitat.

CONCLUSIONS: Our study highlights the importance of accounting for both spatial (i.e. between-population variation) and temporal (i.e. cohort variation) heterogeneity in environmental conditions, especially in early life, to understand the potential for adaptive responses of wild populations to selection.}, } @article {pmid29592795, year = {2018}, author = {Romiguier, J and Rolland, J and Morandin, C and Keller, L}, title = {Phylogenomics of palearctic Formica species suggests a single origin of temporary parasitism and gives insights to the evolutionary pathway toward slave-making behaviour.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {40}, pmid = {29592795}, issn = {1471-2148}, mesh = {Animals ; Ants/*classification/*genetics ; Arctic Regions ; *Behavior, Animal ; Parasites/*classification/*genetics ; *Phylogeny ; *Social Behavior ; Species Specificity ; Symbiosis ; }, abstract = {BACKGROUND: The ants of the Formica genus are classical model species in evolutionary biology. In particular, Darwin used Formica as model species to better understand the evolution of slave-making, a parasitic behaviour where workers of another species are stolen to exploit their workforce. In his book "On the Origin of Species" (1859), Darwin first hypothesized that slave-making behaviour in Formica evolved in incremental steps from a free-living ancestor.

METHODS: The absence of a well-resolved phylogenetic tree of the genus prevent an assessment of whether relationships among Formica subgenera are compatible with this scenario. In this study, we resolve the relationships among the 4 palearctic Formica subgenera (Formica str. s., Coptoformica, Raptiformica and Serviformica) using a phylogenomic dataset of 945 genes for 16 species.

RESULTS: We provide a reference tree resolving the relationships among the main Formica subgenera with high bootstrap supports.

DISCUSSION: The branching order of our tree suggests that the free-living lifestyle is ancestral in the Formica genus and that parasitic colony founding could have evolved a single time, probably acting as a pre-adaptation to slave-making behaviour.

CONCLUSION: This phylogenetic tree provides a solid backbone for future evolutionary studies in the Formica genus and slave-making behaviour.}, } @article {pmid29590394, year = {2018}, author = {Brennan, JJ and Gilmore, TD}, title = {Evolutionary Origins of Toll-like Receptor Signaling.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1576-1587}, doi = {10.1093/molbev/msy050}, pmid = {29590394}, issn = {1537-1719}, abstract = {Toll-like receptors (TLRs) are transmembrane pattern recognition receptors that are best known for their roles in innate immunity for the detection of and defense against microbial pathogens. However, TLRs also have roles in many nonimmune processes, most notably development. TLRs direct both immune and developmental programs by activation of downstream signaling pathways, often by activation of the NF-κB pathway. There are two primary TLR subtypes: 1) TLRs with multiple cysteine clusters in their ectodomain (mccTLRs) and 2) TLRs with a single cysteine cluster in their ectodomain (sccTLRs). For some time, it has been known that TLRs and the biological processes that they control are conserved in organisms from insects to mammals. However, genome and transcriptome sequencing has revealed that many basal metazoans also have TLRs and downstream NF-κB signaling components. In this review, we discuss what is known about the structure, biological function, and downstream signaling pathways of TLRs found in phyla from Porifera through Annelida. From these analyses, we hypothesize that mccTLRs emerged in the phylum Cnidaria, that sccTLRs evolved in the phylum Mollusca, and that TLRs have dual immune and developmental biological functions in organisms as ancient as cnidarians.}, } @article {pmid29590392, year = {2018}, author = {Holliger, C and Nijenhuis, I}, title = {Editorial: Special issue on anaerobic biological dehalogenation.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {6}, pages = {}, doi = {10.1093/femsec/fiy054}, pmid = {29590392}, issn = {1574-6941}, } @article {pmid29590094, year = {2018}, author = {Zhang, H and Liu, CX and Gazibegovic, S and Xu, D and Logan, JA and Wang, G and van Loo, N and Bommer, JDS and de Moor, MWA and Car, D and Op Het Veld, RLM and van Veldhoven, PJ and Koelling, S and Verheijen, MA and Pendharkar, M and Pennachio, DJ and Shojaei, B and Lee, JS and Palmstrøm, CJ and Bakkers, EPAM and Sarma, SD and Kouwenhoven, LP}, title = {Quantized Majorana conductance.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {74-79}, pmid = {29590094}, issn = {1476-4687}, abstract = {Majorana zero-modes-a type of localized quasiparticle-hold great promise for topological quantum computing. Tunnelling spectroscopy in electrical transport is the primary tool for identifying the presence of Majorana zero-modes, for instance as a zero-bias peak in differential conductance. The height of the Majorana zero-bias peak is predicted to be quantized at the universal conductance value of 2e2/h at zero temperature (where e is the charge of an electron and h is the Planck constant), as a direct consequence of the famous Majorana symmetry in which a particle is its own antiparticle. The Majorana symmetry protects the quantization against disorder, interactions and variations in the tunnel coupling. Previous experiments, however, have mostly shown zero-bias peaks much smaller than 2e2/h, with a recent observation of a peak height close to 2e2/h. Here we report a quantized conductance plateau at 2e2/h in the zero-bias conductance measured in indium antimonide semiconductor nanowires covered with an aluminium superconducting shell. The height of our zero-bias peak remains constant despite changing parameters such as the magnetic field and tunnel coupling, indicating that it is a quantized conductance plateau. We distinguish this quantized Majorana peak from possible non-Majorana origins by investigating its robustness to electric and magnetic fields as well as its temperature dependence. The observation of a quantized conductance plateau strongly supports the existence of Majorana zero-modes in the system, consequently paving the way for future braiding experiments that could lead to topological quantum computing.}, } @article {pmid29590093, year = {2018}, author = {Han, Y and Kebschull, JM and Campbell, RAA and Cowan, D and Imhof, F and Zador, AM and Mrsic-Flogel, TD}, title = {The logic of single-cell projections from visual cortex.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {51-56}, pmid = {29590093}, issn = {1476-4687}, support = {R01 DA036913/DA/NIDA NIH HHS/United States ; R01 NS073129/NS/NINDS NIH HHS/United States ; 5R01NS073129/NH/NIH HHS/United States ; 5R01DA036913/NH/NIH HHS/United States ; }, mesh = {Animals ; Axons/*physiology ; Brain Mapping ; Female ; Fluorescence ; High-Throughput Nucleotide Sequencing ; Male ; Mice ; Mice, Inbred C57BL ; Neural Pathways/physiology ; Neuroanatomical Tract-Tracing Techniques ; *Single-Cell Analysis ; Visual Cortex/*cytology/physiology ; }, abstract = {Neocortical areas communicate through extensive axonal projections, but the logic of information transfer remains poorly understood, because the projections of individual neurons have not been systematically characterized. It is not known whether individual neurons send projections only to single cortical areas or distribute signals across multiple targets. Here we determine the projection patterns of 591 individual neurons in the mouse primary visual cortex using whole-brain fluorescence-based axonal tracing and high-throughput DNA sequencing of genetically barcoded neurons (MAPseq). Projections were highly diverse and divergent, collectively targeting at least 18 cortical and subcortical areas. Most neurons targeted multiple cortical areas, often in non-random combinations, suggesting that sub-classes of intracortical projection neurons exist. Our results indicate that the dominant mode of intracortical information transfer is not based on 'one neuron-one target area' mapping. Instead, signals carried by individual cortical neurons are shared across subsets of target areas, and thus concurrently contribute to multiple functional pathways.}, } @article {pmid29590092, year = {2018}, author = {Mills, EL and Ryan, DG and Prag, HA and Dikovskaya, D and Menon, D and Zaslona, Z and Jedrychowski, MP and Costa, ASH and Higgins, M and Hams, E and Szpyt, J and Runtsch, MC and King, MS and McGouran, JF and Fischer, R and Kessler, BM and McGettrick, AF and Hughes, MM and Carroll, RG and Booty, LM and Knatko, EV and Meakin, PJ and Ashford, MLJ and Modis, LK and Brunori, G and Sévin, DC and Fallon, PG and Caldwell, ST and Kunji, ERS and Chouchani, ET and Frezza, C and Dinkova-Kostova, AT and Hartley, RC and Murphy, MP and O'Neill, LA}, title = {Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {113-117}, pmid = {29590092}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; MC_UU_12022/6//Medical Research Council/United Kingdom ; 205455//Wellcome Trust/United Kingdom ; }, mesh = {Alkylation ; Animals ; Anti-Inflammatory Agents/*metabolism/*pharmacology ; Cattle ; Cysteine/chemistry/metabolism ; Cytokines/biosynthesis/immunology ; Feedback, Physiological ; Female ; HEK293 Cells ; Humans ; Hydro-Lyases/biosynthesis ; Interferon-beta/immunology/pharmacology ; Kelch-Like ECH-Associated Protein 1/*chemistry/*metabolism ; Lipopolysaccharides/immunology/pharmacology ; Macrophages/drug effects/metabolism ; Mice ; NF-E2-Related Factor 2/*agonists/*metabolism ; Proteins/metabolism ; Rats ; Rats, Wistar ; Succinates/chemistry/*metabolism ; }, abstract = {The endogenous metabolite itaconate has recently emerged as a regulator of macrophage function, but its precise mechanism of action remains poorly understood. Here we show that itaconate is required for the activation of the anti-inflammatory transcription factor Nrf2 (also known as NFE2L2) by lipopolysaccharide in mouse and human macrophages. We find that itaconate directly modifies proteins via alkylation of cysteine residues. Itaconate alkylates cysteine residues 151, 257, 288, 273 and 297 on the protein KEAP1, enabling Nrf2 to increase the expression of downstream genes with anti-oxidant and anti-inflammatory capacities. The activation of Nrf2 is required for the anti-inflammatory action of itaconate. We describe the use of a new cell-permeable itaconate derivative, 4-octyl itaconate, which is protective against lipopolysaccharide-induced lethality in vivo and decreases cytokine production. We show that type I interferons boost the expression of Irg1 (also known as Acod1) and itaconate production. Furthermore, we find that itaconate production limits the type I interferon response, indicating a negative feedback loop that involves interferons and itaconate. Our findings demonstrate that itaconate is a crucial anti-inflammatory metabolite that acts via Nrf2 to limit inflammation and modulate type I interferons.}, } @article {pmid29590091, year = {2018}, author = {Kim, W and Zhu, W and Hendricks, GL and Van Tyne, D and Steele, AD and Keohane, CE and Fricke, N and Conery, AL and Shen, S and Pan, W and Lee, K and Rajamuthiah, R and Fuchs, BB and Vlahovska, PM and Wuest, WM and Gilmore, MS and Gao, H and Ausubel, FM and Mylonakis, E}, title = {A new class of synthetic retinoid antibiotics effective against bacterial persisters.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {103-107}, pmid = {29590091}, issn = {1476-4687}, support = {P01 AI083214/AI/NIAID NIH HHS/United States ; R35 GM119426/GM/NIGMS NIH HHS/United States ; K99 EY028222/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/adverse effects/*classification/*pharmacology/therapeutic use ; Benzoates/chemistry/pharmacology/therapeutic use/toxicity ; Caenorhabditis elegans/drug effects/microbiology ; Cell Death/drug effects ; Cell Line ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Drug Synergism ; Gentamicins/pharmacology/therapeutic use ; Humans ; Lipid Bilayers/chemistry ; Methicillin-Resistant Staphylococcus aureus/cytology/*drug effects/genetics/growth & development ; Mice ; Microbial Sensitivity Tests ; Molecular Dynamics Simulation ; Mutation ; Naphthols/chemistry/pharmacology/therapeutic use/toxicity ; Retinoids/chemistry/*pharmacology/therapeutic use/toxicity ; Staphylococcal Infections/*drug therapy/*microbiology ; }, abstract = {A challenge in the treatment of Staphylococcus aureus infections is the high prevalence of methicillin-resistant S. aureus (MRSA) strains and the formation of non-growing, dormant 'persister' subpopulations that exhibit high levels of tolerance to antibiotics and have a role in chronic or recurrent infections. As conventional antibiotics are not effective in the treatment of infections caused by such bacteria, novel antibacterial therapeutics are urgently required. Here we used a Caenorhabditis elegans-MRSA infection screen to identify two synthetic retinoids, CD437 and CD1530, which kill both growing and persister MRSA cells by disrupting lipid bilayers. CD437 and CD1530 exhibit high killing rates, synergism with gentamicin, and a low probability of resistance selection. All-atom molecular dynamics simulations demonstrated that the ability of retinoids to penetrate and embed in lipid bilayers correlates with their bactericidal ability. An analogue of CD437 was found to retain anti-persister activity and show an improved cytotoxicity profile. Both CD437 and this analogue, alone or in combination with gentamicin, exhibit considerable efficacy in a mouse model of chronic MRSA infection. With further development and optimization, synthetic retinoids have the potential to become a new class of antimicrobials for the treatment of Gram-positive bacterial infections that are currently difficult to cure.}, } @article {pmid29590090, year = {2018}, author = {Shen, K and Huang, RK and Brignole, EJ and Condon, KJ and Valenstein, ML and Chantranupong, L and Bomaliyamu, A and Choe, A and Hong, C and Yu, Z and Sabatini, DM}, title = {Architecture of the human GATOR1 and GATOR1-Rag GTPases complexes.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {64-69}, pmid = {29590090}, issn = {1476-4687}, support = {R01 CA103866/CA/NCI NIH HHS/United States ; R01 CA129105/CA/NCI NIH HHS/United States ; R37 AI047389/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acids/deficiency ; *Cryoelectron Microscopy ; GTPase-Activating Proteins/antagonists & inhibitors/chemistry/*metabolism/*ultrastructure ; Guanosine Triphosphate/metabolism ; Humans ; Hydrolysis ; Mechanistic Target of Rapamycin Complex 1/antagonists & inhibitors/metabolism ; Models, Molecular ; Monomeric GTP-Binding Proteins/chemistry/*metabolism/*ultrastructure ; Multiprotein Complexes/antagonists & inhibitors/chemistry/*metabolism/*ultrastructure ; Protein Binding ; Protein Domains ; Protein Multimerization ; Protein Subunits/chemistry/metabolism ; Repressor Proteins/chemistry/metabolism/ultrastructure ; Tumor Suppressor Proteins/chemistry/metabolism/ultrastructure ; }, abstract = {Nutrients, such as amino acids and glucose, signal through the Rag GTPases to activate mTORC1. The GATOR1 protein complex-comprising DEPDC5, NPRL2 and NPRL3-regulates the Rag GTPases as a GTPase-activating protein (GAP) for RAGA; loss of GATOR1 desensitizes mTORC1 signalling to nutrient starvation. GATOR1 components have no sequence homology to other proteins, so the function of GATOR1 at the molecular level is currently unknown. Here we used cryo-electron microscopy to solve structures of GATOR1 and GATOR1-Rag GTPases complexes. GATOR1 adopts an extended architecture with a cavity in the middle; NPRL2 links DEPDC5 and NPRL3, and DEPDC5 contacts the Rag GTPase heterodimer. Biochemical analyses reveal that our GATOR1-Rag GTPases structure is inhibitory, and that at least two binding modes must exist between the Rag GTPases and GATOR1. Direct interaction of DEPDC5 with RAGA inhibits GATOR1-mediated stimulation of GTP hydrolysis by RAGA, whereas weaker interactions between the NPRL2-NPRL3 heterodimer and RAGA execute GAP activity. These data reveal the structure of a component of the nutrient-sensing mTORC1 pathway and a non-canonical interaction between a GAP and its substrate GTPase.}, } @article {pmid29590089, year = {2018}, author = {Alemany, A and Florescu, M and Baron, CS and Peterson-Maduro, J and van Oudenaarden, A}, title = {Whole-organism clone tracing using single-cell sequencing.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {108-112}, pmid = {29590089}, issn = {1476-4687}, mesh = {Animal Fins/cytology ; Animals ; Brain/cytology ; CRISPR-Cas Systems/genetics ; *Cell Lineage/genetics ; Cell Tracking/*methods ; Clone Cells/*cytology/*metabolism ; Embryonic Stem Cells/cytology/metabolism ; Eye/cytology ; Female ; Genes, Reporter/genetics ; Hematopoietic Stem Cells/cytology/metabolism ; Male ; Multipotent Stem Cells/cytology/metabolism ; Organ Specificity ; Regeneration ; Sequence Analysis/*methods ; *Single-Cell Analysis ; Transcriptome ; Whole Body Imaging ; Zebrafish/*anatomy & histology/embryology/genetics ; }, abstract = {Embryonic development is a crucial period in the life of a multicellular organism, during which limited sets of embryonic progenitors produce all cells in the adult body. Determining which fate these progenitors acquire in adult tissues requires the simultaneous measurement of clonal history and cell identity at single-cell resolution, which has been a major challenge. Clonal history has traditionally been investigated by microscopically tracking cells during development, monitoring the heritable expression of genetically encoded fluorescent proteins and, more recently, using next-generation sequencing technologies that exploit somatic mutations, microsatellite instability, transposon tagging, viral barcoding, CRISPR-Cas9 genome editing and Cre-loxP recombination. Single-cell transcriptomics provides a powerful platform for unbiased cell-type classification. Here we present ScarTrace, a single-cell sequencing strategy that enables the simultaneous quantification of clonal history and cell type for thousands of cells obtained from different organs of the adult zebrafish. Using ScarTrace, we show that a small set of multipotent embryonic progenitors generate all haematopoietic cells in the kidney marrow, and that many progenitors produce specific cell types in the eyes and brain. In addition, we study when embryonic progenitors commit to the left or right eye. ScarTrace reveals that epidermal and mesenchymal cells in the caudal fin arise from the same progenitors, and that osteoblast-restricted precursors can produce mesenchymal cells during regeneration. Furthermore, we identify resident immune cells in the fin with a distinct clonal origin from other blood cell types. We envision that similar approaches will have major applications in other experimental systems, in which the matching of embryonic clonal origin to adult cell type will ultimately allow reconstruction of how the adult body is built from a single cell.}, } @article {pmid29590088, year = {2018}, author = {Sjodt, M and Brock, K and Dobihal, G and Rohs, PDA and Green, AG and Hopf, TA and Meeske, AJ and Srisuknimit, V and Kahne, D and Walker, S and Marks, DS and Bernhardt, TG and Rudner, DZ and Kruse, AC}, title = {Structure of the peptidoglycan polymerase RodA resolved by evolutionary coupling analysis.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {118-121}, pmid = {29590088}, issn = {1476-4687}, support = {R01 GM076710/GM/NIGMS NIH HHS/United States ; R01 GM106303/GM/NIGMS NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, mesh = {Bacillus subtilis/genetics ; Biocatalysis ; Cell Wall/enzymology/metabolism ; Crystallography, X-Ray/*methods ; Escherichia coli/genetics ; Models, Molecular ; Nucleotidyltransferases/*chemistry/metabolism ; Peptidoglycan/*metabolism ; Protein Domains ; Protein Folding ; Structure-Activity Relationship ; Thermus thermophilus/*enzymology/genetics ; }, abstract = {The shape, elongation, division and sporulation (SEDS) proteins are a large family of ubiquitous and essential transmembrane enzymes with critical roles in bacterial cell wall biology. The exact function of SEDS proteins was for a long time poorly understood, but recent work has revealed that the prototypical SEDS family member RodA is a peptidoglycan polymerase-a role previously attributed exclusively to members of the penicillin-binding protein family. This discovery has made RodA and other SEDS proteins promising targets for the development of next-generation antibiotics. However, little is known regarding the molecular basis of SEDS activity, and no structural data are available for RodA or any homologue thereof. Here we report the crystal structure of Thermus thermophilus RodA at a resolution of 2.9 Å, determined using evolutionary covariance-based fold prediction to enable molecular replacement. The structure reveals a ten-pass transmembrane fold with large extracellular loops, one of which is partially disordered. The protein contains a highly conserved cavity in the transmembrane domain, reminiscent of ligand-binding sites in transmembrane receptors. Mutagenesis experiments in Bacillus subtilis and Escherichia coli show that perturbation of this cavity abolishes RodA function both in vitro and in vivo, indicating that this cavity is catalytically essential. These results provide a framework for understanding bacterial cell wall synthesis and SEDS protein function.}, } @article {pmid29590080, year = {2018}, author = {Wright, M}, title = {Instagram won't solve inequality.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1294}, doi = {10.1126/science.359.6381.1294}, pmid = {29590080}, issn = {1095-9203}, } @article {pmid29590079, year = {2018}, author = {Robert, L and Ollion, J and Robert, J and Song, X and Matic, I and Elez, M}, title = {Mutation dynamics and fitness effects followed in single cells.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1283-1286}, doi = {10.1126/science.aan0797}, pmid = {29590079}, issn = {1095-9203}, mesh = {DNA Mismatch Repair/*genetics ; Escherichia coli/*genetics ; Genes, Lethal ; *Genetic Fitness ; Mutation ; *Mutation Rate ; Single-Cell Analysis/*methods ; Time-Lapse Imaging ; }, abstract = {Mutations have been investigated for more than a century but remain difficult to observe directly in single cells, which limits the characterization of their dynamics and fitness effects. By combining microfluidics, time-lapse imaging, and a fluorescent tag of the mismatch repair system in Escherichia coli, we visualized the emergence of mutations in single cells, revealing Poissonian dynamics. Concomitantly, we tracked the growth and life span of single cells, accumulating ~20,000 mutations genome-wide over hundreds of generations. This analysis revealed that 1% of mutations were lethal; nonlethal mutations displayed a heavy-tailed distribution of fitness effects and were dominated by quasi-neutral mutations with an average cost of 0.3%. Our approach has enabled the investigation of single-cell individuality in mutation rate, mutation fitness costs, and mutation interactions.}, } @article {pmid29590078, year = {2018}, author = {Leeman, DS and Hebestreit, K and Ruetz, T and Webb, AE and McKay, A and Pollina, EA and Dulken, BW and Zhao, X and Yeo, RW and Ho, TT and Mahmoudi, S and Devarajan, K and Passegué, E and Rando, TA and Frydman, J and Brunet, A}, title = {Lysosome activation clears aggregates and enhances quiescent neural stem cell activation during aging.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1277-1283}, pmid = {29590078}, issn = {1095-9203}, support = {T32 GM007365/GM/NIGMS NIH HHS/United States ; T32 CA009302/CA/NCI NIH HHS/United States ; T32 GM008284/GM/NIGMS NIH HHS/United States ; P01 AG036695/AG/NIA NIH HHS/United States ; F31 AG043232/AG/NIA NIH HHS/United States ; R37 AG023806/AG/NIA NIH HHS/United States ; T32 AG047126/AG/NIA NIH HHS/United States ; I01 BX002324/BX/BLRD VA/United States ; R37 GM056433/GM/NIGMS NIH HHS/United States ; }, mesh = {Aging/*physiology ; Animals ; *Cell Division ; *Cellular Senescence ; Lysosomes/*physiology ; Mice ; Mice, Inbred C57BL ; Neural Stem Cells/*physiology ; }, abstract = {In the adult brain, the neural stem cell (NSC) pool comprises quiescent and activated populations with distinct roles. Transcriptomic analysis revealed that quiescent and activated NSCs exhibited differences in their protein homeostasis network. Whereas activated NSCs had active proteasomes, quiescent NSCs contained large lysosomes. Quiescent NSCs from young mice accumulated protein aggregates, and many of these aggregates were stored in large lysosomes. Perturbation of lysosomal activity in quiescent NSCs affected protein-aggregate accumulation and the ability of quiescent NSCs to activate. During aging, quiescent NSCs displayed defects in their lysosomes, increased accumulation of protein aggregates, and reduced ability to activate. Enhancement of the lysosome pathway in old quiescent NSCs cleared protein aggregates and ameliorated the ability of quiescent NSCs to activate, allowing them to regain a more youthful state.}, } @article {pmid29590077, year = {2018}, author = {Grant, SB and Azizian, M and Cook, P and Boano, F and Rippy, MA}, title = {Factoring stream turbulence into global assessments of nitrogen pollution.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1266-1269}, doi = {10.1126/science.aap8074}, pmid = {29590077}, issn = {1095-9203}, mesh = {Ecosystem ; Nitrates/analysis ; Nitrogen/*analysis ; *Nitrogen Cycle ; Rivers/*chemistry ; Water Pollutants, Chemical/*analysis ; Water Pollution, Chemical/*analysis ; }, abstract = {The discharge of excess nitrogen to streams and rivers poses an existential threat to both humans and ecosystems. A seminal study of headwater streams across the United States concluded that in-stream removal of nitrate is controlled primarily by stream chemistry and biology. Reanalysis of these data reveals that stream turbulence (in particular, turbulent mass transfer across the concentration boundary layer) imposes a previously unrecognized upper limit on the rate at which nitrate is removed from streams. The upper limit closely approximates measured nitrate removal rates in streams with low concentrations of this pollutant, a discovery that should inform stream restoration designs and efforts to assess the effects of nitrogen pollution on receiving water quality and the global nitrogen cycle.}, } @article {pmid29590076, year = {2018}, author = {Cesana-Arlotti, N and Martín, A and Téglás, E and Vorobyova, L and Cetnarski, R and Bonatti, LL}, title = {Precursors of logical reasoning in preverbal human infants.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1263-1266}, doi = {10.1126/science.aao3539}, pmid = {29590076}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {*Child Development ; Concept Formation/*physiology ; Eye Movements ; Humans ; Infant ; Problem Solving/*physiology ; }, abstract = {Infants are able to entertain hypotheses about complex events and to modify them rationally when faced with inconsistent evidence. These capacities suggest that infants can use elementary logical representations to frame and prune hypotheses. By presenting scenes containing ambiguities about the identity of an object, here we show that 12- and 19-month-old infants look longer at outcomes that are inconsistent with a logical inference necessary to resolve such ambiguities. At the moment of a potential deduction, infants' pupils dilated, and their eyes moved toward the ambiguous object when inferences could be computed, in contrast to transparent scenes not requiring inferences to identify the object. These oculomotor markers resembled those of adults inspecting similar scenes, suggesting that intuitive and stable logical structures involved in the interpretation of dynamic scenes may be part of the fabric of the human mind.}, } @article {pmid29590075, year = {2018}, author = {Filarsky, M and Fraschka, SA and Niederwieser, I and Brancucci, NMB and Carrington, E and Carrió, E and Moes, S and Jenoe, P and Bártfai, R and Voss, TS}, title = {GDV1 induces sexual commitment of malaria parasites by antagonizing HP1-dependent gene silencing.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1259-1263}, pmid = {29590075}, issn = {1095-9203}, support = {143916//Swiss National Science Foundation/Switzerland ; 157729//Swiss National Science Foundation/Switzerland ; 163258//Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; Chromosomal Proteins, Non-Histone/*metabolism ; Gametogenesis/*genetics ; *Gene Silencing ; Malaria, Falciparum/*parasitology ; Plasmodium falciparum/genetics/*growth & development ; Sex Differentiation/*genetics ; }, abstract = {Malaria is caused by Plasmodium parasites that proliferate in the bloodstream. During each replication cycle, some parasites differentiate into gametocytes, the only forms able to infect the mosquito vector and transmit malaria. Sexual commitment is triggered by activation of AP2-G, the master transcriptional regulator of gametocytogenesis. Heterochromatin protein 1 (HP1)-dependent silencing of ap2-g prevents sexual conversion in proliferating parasites. In this study, we identified Plasmodium falciparum gametocyte development 1 (GDV1) as an upstream activator of sexual commitment. We found that GDV1 targeted heterochromatin and triggered HP1 eviction, thus derepressing ap2-g Expression of GDV1 was responsive to environmental triggers of sexual conversion and controlled via a gdv1 antisense RNA. Hence, GDV1 appears to act as an effector protein that induces sexual differentiation by antagonizing HP1-dependent gene silencing.}, } @article {pmid29590074, year = {2018}, author = {Burgess, MG and McDermott, GR and Owashi, B and Peavey Reeves, LE and Clavelle, T and Ovando, D and Wallace, BP and Lewison, RL and Gaines, SD and Costello, C}, title = {Protecting marine mammals, turtles, and birds by rebuilding global fisheries.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1255-1258}, doi = {10.1126/science.aao4248}, pmid = {29590074}, issn = {1095-9203}, mesh = {Animals ; *Aquatic Organisms ; *Birds ; *Endangered Species ; *Fisheries ; *Mammals ; Population ; *Turtles ; }, abstract = {Reductions in global fishing pressure are needed to end overfishing of target species and maximize the value of fisheries. We ask whether such reductions would also be sufficient to protect non-target species threatened as bycatch. We compare changes in fishing pressure needed to maximize profits from 4713 target fish stocks-accounting for >75% of global catch-to changes in fishing pressure needed to reverse ongoing declines of 20 marine mammal, sea turtle, and seabird populations threatened as bycatch. We project that maximizing fishery profits would halt or reverse declines of approximately half of these threatened populations. Recovering the other populations would require substantially greater effort reductions or targeting improvements. Improving commercial fishery management could thus yield important collateral benefits for threatened bycatch species globally.}, } @article {pmid29590073, year = {2018}, author = {Dong, M and Kathiresan, V and Fenwick, MK and Torelli, AT and Zhang, Y and Caranto, JD and Dzikovski, B and Sharma, A and Lancaster, KM and Freed, JH and Ealick, SE and Hoffman, BM and Lin, H}, title = {Organometallic and radical intermediates reveal mechanism of diphthamide biosynthesis.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1247-1250}, pmid = {29590073}, issn = {1095-9203}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 GM088276/GM/NIGMS NIH HHS/United States ; R01 GM111097/GM/NIGMS NIH HHS/United States ; P41 GM103521/GM/NIGMS NIH HHS/United States ; R35 GM124908/GM/NIGMS NIH HHS/United States ; }, mesh = {Archaeal Proteins/*chemistry ; Carbon/chemistry ; Crystallography, X-Ray ; Histidine/*analogs & derivatives/biosynthesis ; Iron/chemistry ; Iron-Sulfur Proteins/*chemistry ; Organometallic Compounds/chemistry ; Pyrococcus horikoshii/*enzymology ; S-Adenosylmethionine/*chemistry ; }, abstract = {Diphthamide biosynthesis involves a carbon-carbon bond-forming reaction catalyzed by a radical S-adenosylmethionine (SAM) enzyme that cleaves a carbon-sulfur (C-S) bond in SAM to generate a 3-amino-3-carboxypropyl (ACP) radical. Using rapid freezing, we have captured an organometallic intermediate with an iron-carbon (Fe-C) bond between ACP and the enzyme's [4Fe-4S] cluster. In the presence of the substrate protein, elongation factor 2, this intermediate converts to an organic radical, formed by addition of the ACP radical to a histidine side chain. Crystal structures of archaeal diphthamide biosynthetic radical SAM enzymes reveal that the carbon of the SAM C-S bond being cleaved is positioned near the unique cluster Fe, able to react with the cluster. Our results explain how selective C-S bond cleavage is achieved in this radical SAM enzyme.}, } @article {pmid29590072, year = {2018}, author = {Patera, LL and Bianchini, F and Africh, C and Dri, C and Soldano, G and Mariscal, MM and Peressi, M and Comelli, G}, title = {Real-time imaging of adatom-promoted graphene growth on nickel.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1243-1246}, doi = {10.1126/science.aan8782}, pmid = {29590072}, issn = {1095-9203}, abstract = {Single adatoms are expected to participate in many processes occurring at solid surfaces, such as the growth of graphene on metals. We demonstrate, both experimentally and theoretically, the catalytic role played by single metal adatoms during the technologically relevant process of graphene growth on nickel (Ni). The catalytic action of individual Ni atoms at the edges of a growing graphene flake was directly captured by scanning tunneling microscopy imaging at the millisecond time scale, while force field molecular dynamics and density functional theory calculations rationalize the experimental observations. Our results unveil the mechanism governing the activity of a single-atom catalyst at work.}, } @article {pmid29590071, year = {2018}, author = {Panganiban, B and Qiao, B and Jiang, T and DelRe, C and Obadia, MM and Nguyen, TD and Smith, AAA and Hall, A and Sit, I and Crosby, MG and Dennis, PB and Drockenmuller, E and Olvera de la Cruz, M and Xu, T}, title = {Random heteropolymers preserve protein function in foreign environments.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1239-1243}, doi = {10.1126/science.aao0335}, pmid = {29590071}, issn = {1095-9203}, mesh = {Amino Acid Sequence ; Biomimetic Materials/*chemistry ; Molecular Dynamics Simulation ; Polymers/*chemistry ; *Protein Folding ; Proteins/*chemistry ; Solubility ; }, abstract = {The successful incorporation of active proteins into synthetic polymers could lead to a new class of materials with functions found only in living systems. However, proteins rarely function under the conditions suitable for polymer processing. On the basis of an analysis of trends in protein sequences and characteristic chemical patterns on protein surfaces, we designed four-monomer random heteropolymers to mimic intrinsically disordered proteins for protein solubilization and stabilization in non-native environments. The heteropolymers, with optimized composition and statistical monomer distribution, enable cell-free synthesis of membrane proteins with proper protein folding for transport and enzyme-containing plastics for toxin bioremediation. Controlling the statistical monomer distribution in a heteropolymer, rather than the specific monomer sequence, affords a new strategy to interface with biological systems for protein-based biomaterials.}, } @article {pmid29590070, year = {2018}, author = {Bastarache, L and Hughey, JJ and Hebbring, S and Marlo, J and Zhao, W and Ho, WT and Van Driest, SL and McGregor, TL and Mosley, JD and Wells, QS and Temple, M and Ramirez, AH and Carroll, R and Osterman, T and Edwards, T and Ruderfer, D and Velez Edwards, DR and Hamid, R and Cogan, J and Glazer, A and Wei, WQ and Feng, Q and Brilliant, M and Zhao, ZJ and Cox, NJ and Roden, DM and Denny, JC}, title = {Phenotype risk scores identify patients with unrecognized Mendelian disease patterns.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1233-1239}, pmid = {29590070}, issn = {1095-9203}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; T32 HG008341/HG/NHGRI NIH HHS/United States ; F32 HL137385/HL/NHLBI NIH HHS/United States ; R01 GM120523/GM/NIGMS NIH HHS/United States ; T15 LM007450/LM/NLM NIH HHS/United States ; R01 LM010685/LM/NLM NIH HHS/United States ; U01 HG004603/HG/NHGRI NIH HHS/United States ; T15 LM007359/LM/NLM NIH HHS/United States ; U01 HG008672/HG/NHGRI NIH HHS/United States ; R01 HL133786/HL/NHLBI NIH HHS/United States ; R01 GM114128/GM/NIGMS NIH HHS/United States ; P50 GM115305/GM/NIGMS NIH HHS/United States ; U01 HG006378/HG/NHGRI NIH HHS/United States ; UL1 RR024975/RR/NCRR NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; U01 HG009086/HG/NHGRI NIH HHS/United States ; }, mesh = {DNA Mutational Analysis ; Databases, Genetic ; Electronic Health Records ; Exome ; Genetic Association Studies ; Genetic Diseases, Inborn/*diagnosis/*genetics ; *Genetic Predisposition to Disease ; Genetic Variation ; Humans ; Phenotype ; Risk Factors ; }, abstract = {Genetic association studies often examine features independently, potentially missing subpopulations with multiple phenotypes that share a single cause. We describe an approach that aggregates phenotypes on the basis of patterns described by Mendelian diseases. We mapped the clinical features of 1204 Mendelian diseases into phenotypes captured from the electronic health record (EHR) and summarized this evidence as phenotype risk scores (PheRSs). In an initial validation, PheRS distinguished cases and controls of five Mendelian diseases. Applying PheRS to 21,701 genotyped individuals uncovered 18 associations between rare variants and phenotypes consistent with Mendelian diseases. In 16 patients, the rare genetic variants were associated with severe outcomes such as organ transplants. PheRS can augment rare-variant interpretation and may identify subsets of patients with distinct genetic causes for common diseases.}, } @article {pmid29590069, year = {2018}, author = {Peterson, GI}, title = {Postpublication peer review: A crucial tool.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1225-1226}, doi = {10.1126/science.aas9490}, pmid = {29590069}, issn = {1095-9203}, } @article {pmid29590068, year = {2018}, author = {Braje, TJ and Rick, TC and Dillehay, TD and Erlandson, JM and Klein, RG}, title = {Arrival routes of first Americans uncertain-Response.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1225}, doi = {10.1126/science.aar8645}, pmid = {29590068}, issn = {1095-9203}, mesh = {Archaeology ; *Human Migration ; Humans ; North America ; }, } @article {pmid29590067, year = {2018}, author = {Potter, BA and Beaudoin, AB and Haynes, CV and Holliday, VT and Holmes, CE and Ives, JW and Kelly, R and Llamas, B and Malhi, R and Miller, S and Reich, D and Reuther, JD and Schiffels, S and Surovell, T}, title = {Arrival routes of first Americans uncertain.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1224-1225}, doi = {10.1126/science.aar8233}, pmid = {29590067}, issn = {1095-9203}, mesh = {Archaeology ; *Human Migration ; Humans ; North America ; }, } @article {pmid29590066, year = {2018}, author = {Breda, T and Jouini, E and Napp, C}, title = {Societal inequalities amplify gender gaps in math.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1219-1220}, doi = {10.1126/science.aar2307}, pmid = {29590066}, issn = {1095-9203}, mesh = {*Academic Performance ; Female ; *Gender Identity ; Humans ; Mathematics/*education ; *Socioeconomic Factors ; }, } @article {pmid29590065, year = {2018}, author = {Higgins, GS and Boulton, SJ}, title = {Beyond PARP-POLθ as an anticancer target.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1217-1218}, doi = {10.1126/science.aar5149}, pmid = {29590065}, issn = {1095-9203}, mesh = {Antineoplastic Agents/*therapeutic use ; DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA Repair-Deficiency Disorders/*drug therapy/genetics ; DNA-Directed DNA Polymerase/*metabolism ; Genes, BRCA1 ; Homologous Recombination ; Humans ; *Molecular Targeted Therapy ; Neoplasms/*drug therapy/genetics ; Poly(ADP-ribose) Polymerase Inhibitors/*therapeutic use ; Poly(ADP-ribose) Polymerases/*metabolism ; }, } @article {pmid29590064, year = {2018}, author = {Alexander-Katz, A and Van Lehn, RC}, title = {Random copolymers that protect proteins.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1216-1217}, doi = {10.1126/science.aat0155}, pmid = {29590064}, issn = {1095-9203}, mesh = {*Polymers ; }, } @article {pmid29590063, year = {2018}, author = {Halberda, J}, title = {Logic in babies.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1214-1215}, doi = {10.1126/science.aas9183}, pmid = {29590063}, issn = {1095-9203}, mesh = {Humans ; Infant ; *Logic ; }, } @article {pmid29590062, year = {2018}, author = {Weinstein, SB and Buck, JC and Young, HS}, title = {A landscape of disgust.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1213-1214}, doi = {10.1126/science.aas8694}, pmid = {29590062}, issn = {1095-9203}, mesh = {Animals ; *Avoidance Learning ; Biological Evolution ; Fear ; Host-Parasite Interactions ; Humans ; *Infection ; *Parasites ; Risk ; }, } @article {pmid29590061, year = {2018}, author = {Mallet de Lima, CD and Göndör, A}, title = {Circadian organization of the genome.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1212-1213}, doi = {10.1126/science.aat0934}, pmid = {29590061}, issn = {1095-9203}, mesh = {*Circadian Rhythm ; *Genome ; Humans ; }, } @article {pmid29590060, year = {2018}, author = {Millius, A and Ueda, H}, title = {Rhythms: The dark side meets the light.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1210-1211}, doi = {10.1126/science.aat3211}, pmid = {29590060}, issn = {1095-9203}, mesh = {*Circadian Rhythm ; Darkness ; Light ; *Photoperiod ; }, } @article {pmid29590059, year = {2018}, author = {Hvistendahl, M}, title = {Master planner.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1206-1209}, doi = {10.1126/science.359.6381.1206}, pmid = {29590059}, issn = {1095-9203}, } @article {pmid29590058, year = {2018}, author = {Cohen, J}, title = {Concern as HIV prevention strategy languishes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1205}, doi = {10.1126/science.359.6381.1205}, pmid = {29590058}, issn = {1095-9203}, mesh = {Anti-HIV Agents/*therapeutic use ; Australia ; HIV Infections/*prevention & control ; Humans ; Kenya ; Pre-Exposure Prophylaxis/*trends ; United States ; }, } @article {pmid29590057, year = {2018}, author = {Kupferschmidt, K}, title = {Max Planck Society, at a crossroads, seeks new leaders.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1204}, doi = {10.1126/science.359.6381.1204}, pmid = {29590057}, issn = {1095-9203}, } @article {pmid29590056, year = {2018}, author = {Cho, A}, title = {Vibrations used to talk to quantum circuits.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1202-1203}, doi = {10.1126/science.359.6381.1202}, pmid = {29590056}, issn = {1095-9203}, } @article {pmid29590055, year = {2018}, author = {Roberts, L}, title = {Nigeria hit by unprecedented Lassa fever outbreak.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1201-1202}, doi = {10.1126/science.359.6381.1201}, pmid = {29590055}, issn = {1095-9203}, mesh = {Animals ; *Disease Outbreaks ; Humans ; Lassa Fever/*epidemiology ; Lassa virus/*isolation & purification ; Nigeria/epidemiology ; Poverty ; Rats ; World Health Organization ; }, } @article {pmid29590054, year = {2018}, author = {Gibbons, A}, title = {Complex behavior arose at dawn of humans.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1200-1201}, doi = {10.1126/science.359.6381.1200}, pmid = {29590054}, issn = {1095-9203}, mesh = {Anthropology, Cultural ; Fossils ; History, Ancient ; Humans ; Kenya ; Social Behavior/*history ; Technology/*history/instrumentation ; }, } @article {pmid29590053, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1196-1198}, doi = {10.1126/science.359.6381.1196}, pmid = {29590053}, issn = {1095-9203}, } @article {pmid29590052, year = {2018}, author = {Leshner, AI and Dzau, VJ}, title = {Good gun policy needs research.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1195}, doi = {10.1126/science.aat5127}, pmid = {29590052}, issn = {1095-9203}, } @article {pmid29590051, year = {2018}, author = {Huang, RY and Xu, H}, title = {Comment on "Synthesis and characterization of the pentazolate anion cyclo-N5- in (N5)6(H3O)3(NH4)4Cl".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {}, doi = {10.1126/science.aao3672}, pmid = {29590051}, issn = {1095-9203}, abstract = {Zhang et al (Reports, 27 January 2017, p. 374) reported synthesis of a cyclo-N5- ion putatively stabilized in a solid-state salt by hydrogen bonding from surrounding counterions. We performed theoretical calculations suggesting that HN5 would be favored over the anion in the reported pentazolate salt via proton transfer.}, } @article {pmid29590050, year = {2018}, author = {Jiang, C and Zhang, L and Sun, C and Zhang, C and Yang, C and Chen, J and Hu, B}, title = {Response to Comment on "Synthesis and characterization of the pentazolate anion cyclo-N5- in (N5)6(H3O)3(NH4)4Cl".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {}, doi = {10.1126/science.aas8953}, pmid = {29590050}, issn = {1095-9203}, mesh = {*Anions ; *Protons ; }, abstract = {Huang and Xu argue that the cyclo-N5- ion in (N5)6(H3O)3(NH4)4Cl we described in our report is theoretically unfavorable and is instead protonated. Their conclusion is invalid, as they use an improper method to assess the proton transfer in a solid crystal structure. We present an in-depth experimental and theoretical analysis of (N5)6(H3O)3(NH4)4Cl that supports the results in the original paper.}, } @article {pmid29590049, year = {2018}, author = {Ter-Mikaelian, M}, title = {Why our ways parted.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1186}, doi = {10.1126/science.359.6380.1186}, pmid = {29590049}, issn = {1095-9203}, } @article {pmid29590048, year = {2018}, author = {Xu, C and Corces, VG}, title = {Nascent DNA methylome mapping reveals inheritance of hemimethylation at CTCF/cohesin sites.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1166-1170}, doi = {10.1126/science.aan5480}, pmid = {29590048}, issn = {1095-9203}, support = {P01 GM085354/GM/NIGMS NIH HHS/United States ; RC1 GM091388/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; CCCTC-Binding Factor/*metabolism ; Cell Cycle Proteins/*metabolism ; Cell Line ; Chromatin/metabolism ; Chromosomal Proteins, Non-Histone/*metabolism ; Cytosine/*metabolism ; DNA/metabolism ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methylation/*genetics ; DNA Replication ; *Epigenesis, Genetic ; Humans ; }, abstract = {The faithful inheritance of the epigenome is critical for cells to maintain gene expression programs and cellular identity across cell divisions. We mapped strand-specific DNA methylation after replication forks and show maintenance of the vast majority of the DNA methylome within 20 minutes of replication and inheritance of some hemimethylated CpG dinucleotides (hemiCpGs). Mapping the nascent DNA methylome targeted by each of the three DNA methyltransferases (DNMTs) reveals interactions between DNMTs and substrate daughter cytosines en route to maintenance methylation or hemimethylation. Finally, we show the inheritance of hemiCpGs at short regions flanking CCCTC-binding factor (CTCF)/cohesin binding sites in pluripotent cells. Elimination of hemimethylation causes reduced frequency of chromatin interactions emanating from these sites, suggesting a role for hemimethylation as a stable epigenetic mark regulating CTCF-mediated chromatin interactions.}, } @article {pmid29590047, year = {2018}, author = {Manfredo Vieira, S and Hiltensperger, M and Kumar, V and Zegarra-Ruiz, D and Dehner, C and Khan, N and Costa, FRC and Tiniakou, E and Greiling, T and Ruff, W and Barbieri, A and Kriegel, C and Mehta, SS and Knight, JR and Jain, D and Goodman, AL and Kriegel, MA}, title = {Translocation of a gut pathobiont drives autoimmunity in mice and humans.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1156-1161}, pmid = {29590047}, issn = {1095-9203}, support = {T32 DK007017/DK/NIDDK NIH HHS/United States ; K08 AI095318/AI/NIAID NIH HHS/United States ; UL1 RR024139/RR/NCRR NIH HHS/United States ; T32 AI007019/AI/NIAID NIH HHS/United States ; P30 DK079310/DK/NIDDK NIH HHS/United States ; S10 OD018521/OD/NIH HHS/United States ; R01 AI118855/AI/NIAID NIH HHS/United States ; P30 AR053495/AR/NIAMS NIH HHS/United States ; P30 DK034989/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Autoantibodies/immunology ; Autoimmune Diseases/*genetics/*microbiology ; Autoimmunity/*genetics/immunology ; *Bacterial Translocation ; Bacterial Vaccines/immunology ; DNA, Bacterial/analysis ; Enterococcus/drug effects/immunology/*physiology ; Gastrointestinal Microbiome/*physiology ; *Genetic Predisposition to Disease ; Hepatocytes/microbiology ; Humans ; Liver/microbiology ; Mice ; T-Lymphocytes/immunology ; }, abstract = {Despite multiple associations between the microbiota and immune diseases, their role in autoimmunity is poorly understood. We found that translocation of a gut pathobiont, Enterococcus gallinarum, to the liver and other systemic tissues triggers autoimmune responses in a genetic background predisposing to autoimmunity. Antibiotic treatment prevented mortality in this model, suppressed growth of E. gallinarum in tissues, and eliminated pathogenic autoantibodies and T cells. Hepatocyte-E. gallinarum cocultures induced autoimmune-promoting factors. Pathobiont translocation in monocolonized and autoimmune-prone mice induced autoantibodies and caused mortality, which could be prevented by an intramuscular vaccine targeting the pathobiont. E. gallinarum-specific DNA was recovered from liver biopsies of autoimmune patients, and cocultures with human hepatocytes replicated the murine findings; hence, similar processes apparently occur in susceptible humans. These discoveries show that a gut pathobiont can translocate and promote autoimmunity in genetically predisposed hosts.}, } @article {pmid29590046, year = {2018}, author = {Zhao, L and Zhang, F and Ding, X and Wu, G and Lam, YY and Wang, X and Fu, H and Xue, X and Lu, C and Ma, J and Yu, L and Xu, C and Ren, Z and Xu, Y and Xu, S and Shen, H and Zhu, X and Shi, Y and Shen, Q and Dong, W and Liu, R and Ling, Y and Zeng, Y and Wang, X and Zhang, Q and Wang, J and Wang, L and Wu, Y and Zeng, B and Wei, H and Zhang, M and Peng, Y and Zhang, C}, title = {Gut bacteria selectively promoted by dietary fibers alleviate type 2 diabetes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1151-1156}, doi = {10.1126/science.aao5774}, pmid = {29590046}, issn = {1095-9203}, mesh = {Adult ; Aged ; Bacteria/classification/genetics/metabolism ; China ; Diabetes Mellitus, Type 2/*therapy ; Diet ; Dietary Fiber/*metabolism ; Fatty Acids, Volatile/*metabolism ; Feces ; Female ; Fermentation ; *Gastrointestinal Microbiome ; Glucagon-Like Peptide 1/metabolism ; Glycated Hemoglobin A/analysis ; Humans ; Hydrogen Sulfide/metabolism ; Indoles/metabolism ; Male ; Metagenomics ; Middle Aged ; }, abstract = {The gut microbiota benefits humans via short-chain fatty acid (SCFA) production from carbohydrate fermentation, and deficiency in SCFA production is associated with type 2 diabetes mellitus (T2DM). We conducted a randomized clinical study of specifically designed isoenergetic diets, together with fecal shotgun metagenomics, to show that a select group of SCFA-producing strains was promoted by dietary fibers and that most other potential producers were either diminished or unchanged in patients with T2DM. When the fiber-promoted SCFA producers were present in greater diversity and abundance, participants had better improvement in hemoglobin A1c levels, partly via increased glucagon-like peptide-1 production. Promotion of these positive responders diminished producers of metabolically detrimental compounds such as indole and hydrogen sulfide. Targeted restoration of these SCFA producers may present a novel ecological approach for managing T2DM.}, } @article {pmid29590045, year = {2018}, author = {Vosoughi, S and Roy, D and Aral, S}, title = {The spread of true and false news online.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1146-1151}, doi = {10.1126/science.aap9559}, pmid = {29590045}, issn = {1095-9203}, abstract = {We investigated the differential diffusion of all of the verified true and false news stories distributed on Twitter from 2006 to 2017. The data comprise ~126,000 stories tweeted by ~3 million people more than 4.5 million times. We classified news as true or false using information from six independent fact-checking organizations that exhibited 95 to 98% agreement on the classifications. Falsehood diffused significantly farther, faster, deeper, and more broadly than the truth in all categories of information, and the effects were more pronounced for false political news than for false news about terrorism, natural disasters, science, urban legends, or financial information. We found that false news was more novel than true news, which suggests that people were more likely to share novel information. Whereas false stories inspired fear, disgust, and surprise in replies, true stories inspired anticipation, sadness, joy, and trust. Contrary to conventional wisdom, robots accelerated the spread of true and false news at the same rate, implying that false news spreads more than the truth because humans, not robots, are more likely to spread it.}, } @article {pmid29590044, year = {2018}, author = {Krupic, J and Bauza, M and Burton, S and O'Keefe, J}, title = {Local transformations of the hippocampal cognitive map.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1143-1146}, doi = {10.1126/science.aao4960}, pmid = {29590044}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; R21 AT003212/AT/NCCIH NIH HHS/United States ; }, mesh = {Animals ; *Brain Mapping ; *Cognition ; Hippocampus/*cytology/*physiology ; Male ; Rats ; Rats, Inbred Strains ; }, abstract = {Grid cells are neurons active in multiple fields arranged in a hexagonal lattice and are thought to represent the "universal metric for space." However, they become nonhomogeneously distorted in polarized enclosures, which challenges this view. We found that local changes to the configuration of the enclosure induce individual grid fields to shift in a manner inversely related to their distance from the reconfigured boundary. The grid remained primarily anchored to the unchanged stable walls and showed a nonuniform rescaling. Shifts in simultaneously recorded colocalized grid fields were strongly correlated, which suggests that the readout of the animal's position might still be intact. Similar field shifts were also observed in place and boundary cells-albeit of greater magnitude and more pronounced closer to the reconfigured boundary-which suggests that there is no simple one-to-one relationship between these three different cell types.}, } @article {pmid29590043, year = {2018}, author = {Moore, JK and Fu, W and Primeau, F and Britten, GL and Lindsay, K and Long, M and Doney, SC and Mahowald, N and Hoffman, F and Randerson, JT}, title = {Sustained climate warming drives declining marine biological productivity.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1139-1143}, doi = {10.1126/science.aao6379}, pmid = {29590043}, issn = {1095-9203}, mesh = {Animals ; *Carbon Cycle ; *Climate Change ; *Fisheries ; Hot Temperature ; Ice Cover ; Oceans and Seas ; Wind ; }, abstract = {Climate change projections to the year 2100 may miss physical-biogeochemical feedbacks that emerge later from the cumulative effects of climate warming. In a coupled climate simulation to the year 2300, the westerly winds strengthen and shift poleward, surface waters warm, and sea ice disappears, leading to intense nutrient trapping in the Southern Ocean. The trapping drives a global-scale nutrient redistribution, with net transfer to the deep ocean. Ensuing surface nutrient reductions north of 30°S drive steady declines in primary production and carbon export (decreases of 24 and 41%, respectively, by 2300). Potential fishery yields, constrained by lower-trophic-level productivity, decrease by more than 20% globally and by nearly 60% in the North Atlantic. Continued high levels of greenhouse gas emissions could suppress marine biological productivity for a millennium.}, } @article {pmid29590042, year = {2018}, author = {Tschauner, O and Huang, S and Greenberg, E and Prakapenka, VB and Ma, C and Rossman, GR and Shen, AH and Zhang, D and Newville, M and Lanzirotti, A and Tait, K}, title = {Ice-VII inclusions in diamonds: Evidence for aqueous fluid in Earth's deep mantle.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1136-1139}, doi = {10.1126/science.aao3030}, pmid = {29590042}, issn = {1095-9203}, abstract = {Water-rich regions in Earth's deeper mantle are suspected to play a key role in the global water budget and the mobility of heat-generating elements. We show that ice-VII occurs as inclusions in natural diamond and serves as an indicator for such water-rich regions. Ice-VII, the residue of aqueous fluid present during growth of diamond, crystallizes upon ascent of the host diamonds but remains at pressures as high as 24 gigapascals; it is now recognized as a mineral by the International Mineralogical Association. In particular, ice-VII in diamonds points toward fluid-rich locations in the upper transition zone and around the 660-kilometer boundary.}, } @article {pmid29590041, year = {2018}, author = {Xie, S and Tu, L and Han, Y and Huang, L and Kang, K and Lao, KU and Poddar, P and Park, C and Muller, DA and DiStasio, RA and Park, J}, title = {Coherent, atomically thin transition-metal dichalcogenide superlattices with engineered strain.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1131-1136}, doi = {10.1126/science.aao5360}, pmid = {29590041}, issn = {1095-9203}, abstract = {Epitaxy forms the basis of modern electronics and optoelectronics. We report coherent atomically thin superlattices in which different transition metal dichalcogenide monolayers-despite large lattice mismatches-are repeated and laterally integrated without dislocations within the monolayer plane. Grown by an omnidirectional epitaxy, these superlattices display fully matched lattice constants across heterointerfaces while maintaining an isotropic lattice structure and triangular symmetry. This strong epitaxial strain is precisely engineered via the nanoscale supercell dimensions, thereby enabling broad tuning of the optical properties and producing photoluminescence peak shifts as large as 250 millielectron volts. We present theoretical models to explain this coherent growth and the energetic interplay governing the ripple formation in these strained monolayers. Such coherent superlattices provide building blocks with targeted functionalities at the atomically thin limit.}, } @article {pmid29590040, year = {2018}, author = {Woutersen, S and Ensing, B and Hilbers, M and Zhao, Z and Angell, CA}, title = {A liquid-liquid transition in supercooled aqueous solution related to the HDA-LDA transition.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1127-1131}, doi = {10.1126/science.aao7049}, pmid = {29590040}, issn = {1095-9203}, abstract = {Simulations and theory suggest that the thermodynamic anomalies of water may be related to a phase transition between two supercooled liquid states, but so far this phase transition has not been observed experimentally because of preemptive ice crystallization. We used calorimetry, infrared spectroscopy, and molecular dynamics simulations to investigate a water-rich hydrazinium trifluoroacetate solution in which the local hydrogen bond structure surrounding a water molecule resembles that in neat water at elevated pressure, but which does not crystallize upon cooling. Instead, this solution underwent a sharp, reversible phase transition between two homogeneous liquid states. The hydrogen-bond structures of these two states are similar to those established for high- and low-density amorphous (HDA and LDA) water. Such structural similarity supports theories that predict a similar sharp transition in pure water under pressure if ice crystallization could be suppressed.}, } @article {pmid29590039, year = {2018}, author = {McLean, W}, title = {Toward a true cure for hearing impairment.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1113}, doi = {10.1126/science.aat0966}, pmid = {29590039}, issn = {1095-9203}, mesh = {Animals ; Hair Cells, Auditory, Inner/*physiology ; Hearing Loss/*therapy ; Humans ; Mice ; Regeneration ; Stem Cells/*physiology ; Translational Medical Research ; }, } @article {pmid29590038, year = {2018}, author = {Sampaziotis, F}, title = {Building better bile ducts.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1113}, doi = {10.1126/science.aat0964}, pmid = {29590038}, issn = {1095-9203}, mesh = {Animals ; Bile Duct Diseases/*therapy ; Bile Ducts/*cytology/growth & development/*transplantation ; Cell Culture Techniques ; Drug Evaluation, Preclinical ; Humans ; In Vitro Techniques ; Mice ; *Organoids ; Tissue Engineering/*methods ; }, } @article {pmid29590037, year = {2018}, author = {Naik, S}, title = {The healing power of painful memories.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1113}, doi = {10.1126/science.aat0963}, pmid = {29590037}, issn = {1095-9203}, mesh = {Aminoquinolines/pharmacology ; Animals ; Chromatin/chemistry/metabolism ; Epidermal Cells ; Epidermis/*immunology ; Humans ; Imiquimod ; *Immunologic Memory ; Inflammation/chemically induced/pathology/*therapy ; Mice ; Protein Domains ; *Regeneration ; Stem Cells/*immunology/physiology ; Toll-Like Receptor 7/agonists ; }, } @article {pmid29590036, year = {2018}, author = {Roybal, KT}, title = {Refining cell therapy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1112-1113}, doi = {10.1126/science.aat0962}, pmid = {29590036}, issn = {1095-9203}, mesh = {Animals ; *Cell Engineering ; Cell- and Tissue-Based Therapy/*methods ; Humans ; Neoplasms/*therapy ; *Receptors, Notch/chemistry/genetics ; *Recombinant Fusion Proteins/chemistry/genetics ; T-Lymphocytes/*transplantation ; }, } @article {pmid29590035, year = {2018}, author = {Somma, LA}, title = {Possible brooding of pterosaur parents.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1111}, doi = {10.1126/science.aas9153}, pmid = {29590035}, issn = {1095-9203}, mesh = {Animals ; Behavior, Animal ; Dinosaurs/*anatomy & histology ; Humans ; }, } @article {pmid29590034, year = {2018}, author = {Balogun, WG and Seeni, A}, title = {Nigeria's new GDP means scientists suffer.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1111}, doi = {10.1126/science.aar8549}, pmid = {29590034}, issn = {1095-9203}, } @article {pmid29590033, year = {2018}, author = {Ale, SB and Mishra, C}, title = {The snow leopard's questionable comeback.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1110}, doi = {10.1126/science.aas9893}, pmid = {29590033}, issn = {1095-9203}, mesh = {Animals ; *Endangered Species ; *Extinction, Biological ; *Felidae ; Population ; }, } @article {pmid29590032, year = {2018}, author = {Smith, LM and Kelleher, NL}, title = {Proteoforms as the next proteomics currency.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1106-1107}, pmid = {29590032}, issn = {1095-9203}, support = {P41 GM108569/GM/NIGMS NIH HHS/United States ; R01 GM114292/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Genetic Variation ; Humans ; Peptides/chemistry ; Protein Isoforms/*chemistry/*genetics ; Protein Processing, Post-Translational ; *Proteomics ; }, } @article {pmid29590031, year = {2018}, author = {Li, XH and Chavali, PL and Babu, MM}, title = {Capturing dynamic protein interactions.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1105-1106}, doi = {10.1126/science.aat0576}, pmid = {29590031}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {*Biophysical Phenomena ; *Protein Binding ; }, } @article {pmid29590030, year = {2018}, author = {Laufkötter, C and Gruber, N}, title = {Will marine productivity wane?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1103-1104}, doi = {10.1126/science.aat0795}, pmid = {29590030}, issn = {1095-9203}, } @article {pmid29590029, year = {2018}, author = {Sharif, J and Koseki, H}, title = {Hemimethylation: DNA's lasting odd couple.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1102-1103}, doi = {10.1126/science.aat0789}, pmid = {29590029}, issn = {1095-9203}, mesh = {*DNA, Viral ; }, } @article {pmid29590028, year = {2018}, author = {Winkler, F and Wick, W}, title = {Harmful networks in the brain and beyond.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1100-1101}, doi = {10.1126/science.aar5555}, pmid = {29590028}, issn = {1095-9203}, mesh = {Animals ; Brain Neoplasms/drug therapy/*pathology ; *Cell Communication ; Cell Surface Extensions/*pathology ; Disease Progression ; Drosophila melanogaster ; Drug Resistance, Neoplasm ; Glioblastoma/drug therapy/*pathology ; Humans ; Nanotubes ; }, } @article {pmid29590027, year = {2018}, author = {Kelly, RG and Sperling, SR}, title = {Diverging roads to the heart.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1098-1099}, doi = {10.1126/science.aat0230}, pmid = {29590027}, issn = {1095-9203}, mesh = {*Heart ; Humans ; }, } @article {pmid29590026, year = {2018}, author = {Citi, S}, title = {Intestinal barriers protect against disease.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1097-1098}, doi = {10.1126/science.aat0835}, pmid = {29590026}, issn = {1095-9203}, mesh = {Humans ; *Intestinal Mucosa ; *Intestines ; }, } @article {pmid29590025, year = {2018}, author = {Lazer, DMJ and Baum, MA and Benkler, Y and Berinsky, AJ and Greenhill, KM and Menczer, F and Metzger, MJ and Nyhan, B and Pennycook, G and Rothschild, D and Schudson, M and Sloman, SA and Sunstein, CR and Thorson, EA and Watts, DJ and Zittrain, JL}, title = {The science of fake news.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1094-1096}, doi = {10.1126/science.aao2998}, pmid = {29590025}, issn = {1095-9203}, } @article {pmid29590024, year = {2018}, author = {Vogel, G}, title = {Fever dilemma.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1090-1092}, doi = {10.1126/science.359.6380.1090}, pmid = {29590024}, issn = {1095-9203}, mesh = {*Developing Countries ; Diagnosis, Differential ; Diagnostic Tests, Routine ; Fever/*diagnosis/*drug therapy/microbiology/parasitology ; *Health Systems Plans ; Humans ; Infant ; Malaria/complications/diagnosis/drug therapy ; }, } @article {pmid29590023, year = {2018}, author = {Cornwall, W}, title = {Looking for love.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1086-1089}, doi = {10.1126/science.359.6380.1086}, pmid = {29590023}, issn = {1095-9203}, mesh = {Animals ; Asia ; *Endangered Species ; *Falconiformes ; }, } @article {pmid29590022, year = {2018}, author = {Normile, D}, title = {China hones plans for ambitious x-ray probe.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1085}, doi = {10.1126/science.359.6380.1085}, pmid = {29590022}, issn = {1095-9203}, } @article {pmid29590021, year = {2018}, author = {Reese, A}, title = {Slow coolant phaseout could worsen warming.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1084}, doi = {10.1126/science.359.6380.1084}, pmid = {29590021}, issn = {1095-9203}, } @article {pmid29590020, year = {2018}, author = {Underwood, E}, title = {Study undercuts claims of new neurons in adult brains.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1083}, doi = {10.1126/science.359.6380.1083}, pmid = {29590020}, issn = {1095-9203}, mesh = {Adult ; Brain/*cytology/*growth & development ; Humans ; Infant, Newborn ; *Neurogenesis ; Neurons/*cytology ; }, } @article {pmid29590019, year = {2018}, author = {Voosen, P}, title = {Saildrone fleet could help replace aging buoys.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1082-1083}, doi = {10.1126/science.359.6380.1082}, pmid = {29590019}, issn = {1095-9203}, } @article {pmid29590018, year = {2018}, author = {Vogel, G}, title = {Germany's new government makes big promises.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1081}, doi = {10.1126/science.359.6380.1081}, pmid = {29590018}, issn = {1095-9203}, } @article {pmid29590017, year = {2018}, author = {Service, RF}, title = {Lithium-sulfur batteries poised for leap.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1080-1081}, doi = {10.1126/science.359.6380.1080}, pmid = {29590017}, issn = {1095-9203}, } @article {pmid29590016, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1076-1078}, doi = {10.1126/science.359.6380.1076}, pmid = {29590016}, issn = {1095-9203}, } @article {pmid29590015, year = {2018}, author = {Berkley, S}, title = {Health security's blind spot.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1075}, doi = {10.1126/science.aat4714}, pmid = {29590015}, issn = {1095-9203}, mesh = {*Communicable Disease Control ; Communicable Diseases/*diagnosis/*epidemiology ; Disease Outbreaks/*prevention & control ; Early Diagnosis ; *Global Health ; Humans ; *Vaccines ; }, } @article {pmid29590014, year = {2018}, author = {}, title = {Cover stories: Visualizing the spread of true and false news on social media.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {}, doi = {10.1126/science.aat4382}, pmid = {29590014}, issn = {1095-9203}, } @article {pmid29590013, year = {2018}, author = {Rosas, A and Ríos, L and Estalrrich, A and Liversidge, H and García-Tabernero, A and Huguet, R and Cardoso, H and Bastir, M and Lalueza-Fox, C and de la Rasilla, M and Dean, C}, title = {Response to Comment on "The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidrón (Spain)".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {}, doi = {10.1126/science.aar3820}, pmid = {29590013}, issn = {1095-9203}, mesh = {Brain ; *Fossils ; Hominidae ; Humans ; Male ; *Neanderthals ; Skeleton ; Spain ; }, abstract = {The comment by DeSilva challenges our suggestion that brain growth of the El Sidrón J1 Neandertal was still incomplete at 7.7 years of age. Evidence suggests that endocranial volume is likely to represent less than 90% adult size at El Sidrón as well as Neandertal male plus Krapina samples, in line with further evidence from endocranial surface histology and dural sinus groove size.}, } @article {pmid29590012, year = {2018}, author = {DeSilva, JM}, title = {Comment on "The growth pattern of Neandertals, reconstructed from a juvenile skeleton from El Sidrón (Spain)".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {}, doi = {10.1126/science.aar3611}, pmid = {29590012}, issn = {1095-9203}, mesh = {*Biological Evolution ; Fossils ; Hominidae ; Humans ; *Neanderthals ; Skeleton ; Spain ; }, abstract = {Rosas et al (Reports, 22 September 2017, p. 1282) calculate El Sidrón J1 to have reached only 87.5% of its adult brain size. This finding is based on an overestimation of Neandertal brain size. Pairwise comparisons with a larger sample of Neandertal fossils reveal that it is unlikely that the brain of El Sidrón would have grown appreciably larger.}, } @article {pmid29590011, year = {2018}, author = {Stanton, BZ and Chory, EJ and Crabtree, GR}, title = {Chemically induced proximity in biology and medicine.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {}, doi = {10.1126/science.aao5902}, pmid = {29590011}, issn = {1095-9203}, support = {R01 CA163915/CA/NCI NIH HHS/United States ; R37 NS046789/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Biological Mimicry ; CRISPR-Cas Systems ; Cell- and Tissue-Based Therapy/*trends ; Chromatin/chemistry ; Genetic Therapy/*trends ; Humans ; Ligands ; Protein Folding ; Protein Processing, Post-Translational ; Proteins/*chemistry ; Proteolysis ; Signal Transduction ; Tacrolimus/analogs & derivatives/pharmacology ; Transcription, Genetic ; }, abstract = {Proximity, or the physical closeness of molecules, is a pervasive regulatory mechanism in biology. For example, most posttranslational modifications such as phosphorylation, methylation, and acetylation promote proximity of molecules to play deterministic roles in cellular processes. To understand the role of proximity in biologic mechanisms, chemical inducers of proximity (CIPs) were developed to synthetically model biologically regulated recruitment. Chemically induced proximity allows for precise temporal control of transcription, signaling cascades, chromatin regulation, protein folding, localization, and degradation, as well as a host of other biologic processes. A systematic analysis of CIPs in basic research, coupled with recent technological advances utilizing CRISPR, distinguishes roles of causality from coincidence and allows for mathematical modeling in synthetic biology. Recently, induced proximity has provided new avenues of gene therapy and emerging advances in cancer treatment.}, } @article {pmid29589959, year = {2018}, author = {Andorfer, MC and Lewis, JC}, title = {Understanding and Improving the Activity of Flavin-Dependent Halogenases via Random and Targeted Mutagenesis.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {159-185}, pmid = {29589959}, issn = {1545-4509}, support = {R01 GM115665/GM/NIGMS NIH HHS/United States ; T32 GM008720/GM/NIGMS NIH HHS/United States ; }, abstract = {Flavin-dependent halogenases (FDHs) catalyze the halogenation of organic substrates by coordinating reactions of reduced flavin, molecular oxygen, and chloride. Targeted and random mutagenesis of these enzymes have been used to both understand and alter their reactivity. These studies have led to insights into residues essential for catalysis and FDH variants with improved stability, expanded substrate scope, and altered site selectivity. Mutations throughout FDH structures have contributed to all of these advances. More recent studies have sought to rationalize the impact of these mutations on FDH function and to identify new FDHs to deepen our understanding of this enzyme class and to expand their utility for biocatalytic applications.}, } @article {pmid29589958, year = {2018}, author = {Sharifi, S and Bierhoff, H}, title = {Regulation of RNA Polymerase I Transcription in Development, Disease, and Aging.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {51-73}, doi = {10.1146/annurev-biochem-062917-012612}, pmid = {29589958}, issn = {1545-4509}, abstract = {Ribosome biogenesis is a complex and highly energy-demanding process that requires the concerted action of all three nuclear RNA polymerases (Pol I-III) in eukaryotes. The three largest ribosomal RNAs (rRNAs) originate from a precursor transcript (pre-rRNA) that is encoded by multicopy genes located in the nucleolus. Transcription of these rRNA genes (rDNA) by Pol I is the key regulation step in ribosome production and is tightly controlled by an intricate network of signaling pathways and epigenetic mechanisms. In this article, we give an overview of the composition of the basal Pol I machinery and rDNA chromatin. We discuss rRNA gene regulation in response to environmental signals and developmental cues and focus on perturbations occurring in diseases linked to either excessive or limited rRNA levels. Finally, we discuss the emerging view that rDNA integrity and activity may be involved in the aging process.}, } @article {pmid29589566, year = {2018}, author = {Miannay, B and Minvielle, S and Magrangeas, F and Guziolowski, C}, title = {Constraints on signaling network logic reveal functional subgraphs on Multiple Myeloma OMIC data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 3}, pages = {32}, pmid = {29589566}, issn = {1752-0509}, support = {P01 CA155258/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: The integration of gene expression profiles (GEPs) and large-scale biological networks derived from pathways databases is a subject which is being widely explored. Existing methods are based on network distance measures among significantly measured species. Only a small number of them include the directionality and underlying logic existing in biological networks. In this study we approach the GEP-networks integration problem by considering the network logic, however our approach does not require a prior species selection according to their gene expression level.

RESULTS: We start by modeling the biological network representing its underlying logic using Logic Programming. This model points to reachable network discrete states that maximize a notion of harmony between the molecular species active or inactive possible states and the directionality of the pathways reactions according to their activator or inhibitor control role. Only then, we confront these network states with the GEP. From this confrontation independent graph components are derived, each of them related to a fixed and optimal assignment of active or inactive states. These components allow us to decompose a large-scale network into subgraphs and their molecular species state assignments have different degrees of similarity when compared to the same GEP. We apply our method to study the set of possible states derived from a subgraph from the NCI-PID Pathway Interaction Database. This graph links Multiple Myeloma (MM) genes to known receptors for this blood cancer.

CONCLUSION: We discover that the NCI-PID MM graph had 15 independent components, and when confronted to 611 MM GEPs, we find 1 component as being more specific to represent the difference between cancer and healthy profiles.}, } @article {pmid29589565, year = {2018}, author = {Hall-Swan, S and Crawford, J and Newman, R and Cowen, LJ}, title = {Detangling PPI networks to uncover functionally meaningful clusters.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 3}, pages = {24}, pmid = {29589565}, issn = {1752-0509}, abstract = {BACKGROUND: Decomposing a protein-protein interaction network (PPI network) into non-overlapping clusters or communities, sometimes called "network modules," is an important way to explore functional roles of sets of genes. When the method to accomplish this decomposition is solely based on purely graph-theoretic measures of the interconnection structure of the network, this is often called unsupervised clustering or community detection. In this study, we compare unsupervised computational methods for decomposing a PPI network into non-overlapping modules. A method is preferred if it results in a large proportion of nodes being assigned to functionally meaningful modules, as measured by functional enrichment over terms from the Gene Ontology (GO).

RESULTS: We compare the performance of three popular community detection algorithms with the same algorithms run after the network is pre-processed by removing and reweighting based on the diffusion state distance (DSD) between pairs of nodes in the network. We call this "detangling" the network. In almost all cases, we find that detangling the network based on the DSD distance reweighting provides more meaningful clusters.

CONCLUSIONS: Re-embedding using the DSD distance metric, before applying standard community detection algorithms, can assist in uncovering GO functionally enriched clusters in the yeast PPI network.}, } @article {pmid29589564, year = {2018}, author = {Karbalayghareh, A and Braga-Neto, U and Dougherty, ER}, title = {Intrinsically Bayesian robust classifier for single-cell gene expression trajectories in gene regulatory networks.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 3}, pages = {23}, pmid = {29589564}, issn = {1752-0509}, abstract = {BACKGROUND: Expression-based phenotype classification using either microarray or RNA-Seq measurements suffers from a lack of specificity because pathway timing is not revealed and expressions are averaged across groups of cells. This paper studies expression-based classification under the assumption that single-cell measurements are sampled at a sufficient rate to detect regulatory timing. Thus, observations are expression trajectories. In effect, classification is performed on data generated by an underlying gene regulatory network.

RESULTS: Network regulation is modeled via a Boolean network with perturbation, regulation not fully determined owing to inherent biological randomness. The binary assumption is not critical because the resulting Markov chain characterizes expression trajectories. We assume a partially known Gaussian observation model belonging to an uncertainty class of models. We derive the intrinsically Bayesian robust classifier to discriminate between wild-type and mutated networks based on expression trajectories. The classifier minimizes the expected error across the uncertainty class relative to the prior distribution. We test it using a mammalian cell-cycle model, discriminating between the normal network and one in which gene p27 is mutated, thereby producing a cancerous phenotype. Tests examine all model aspects, including trajectory length, perturbation probability, and the hyperparameters governing the prior distribution over the uncertainty class.

CONCLUSIONS: Simulations show the rates at which the expected error is diminished by smaller perturbation probability, longer trajectories, and hyperparameters that tighten the prior distribution relative to the unknown true network. For average-expression measurement, methods have been proposed to obtain prior distributions. These should be extended to the more mathematically difficult, but more informative, expression trajectories.}, } @article {pmid29589561, year = {2018}, author = {Xu, EL and Qian, X and Yu, Q and Zhang, H and Cui, S}, title = {Feature selection with interactions in logistic regression models using multivariate synergies for a GWAS application.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 4}, pages = {170}, pmid = {29589561}, issn = {1471-2164}, support = {R21 DK092845/DK/NIDDK NIH HHS/United States ; }, mesh = {Algorithms ; Case-Control Studies ; Computational Biology/*methods ; Computer Simulation ; Diabetes Mellitus, Type 1/*genetics ; Genetic Markers ; Genetic Predisposition to Disease ; *Genome-Wide Association Study ; Humans ; Logistic Models ; Models, Genetic ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Genotype-phenotype association has been one of the long-standing problems in bioinformatics. Identifying both the marginal and epistatic effects among genetic markers, such as Single Nucleotide Polymorphisms (SNPs), has been extensively integrated in Genome-Wide Association Studies (GWAS) to help derive "causal" genetic risk factors and their interactions, which play critical roles in life and disease systems. Identifying "synergistic" interactions with respect to the outcome of interest can help accurate phenotypic prediction and understand the underlying mechanism of system behavior. Many statistical measures for estimating synergistic interactions have been proposed in the literature for such a purpose. However, except for empirical performance, there is still no theoretical analysis on the power and limitation of these synergistic interaction measures.

RESULTS: In this paper, it is shown that the existing information-theoretic multivariate synergy depends on a small subset of the interaction parameters in the model, sometimes on only one interaction parameter. In addition, an adjusted version of multivariate synergy is proposed as a new measure to estimate the interactive effects, with experiments conducted over both simulated data sets and a real-world GWAS data set to show the effectiveness.

CONCLUSIONS: We provide rigorous theoretical analysis and empirical evidence on why the information-theoretic multivariate synergy helps with identifying genetic risk factors via synergistic interactions. We further establish the rigorous sample complexity analysis on detecting interactive effects, confirmed by both simulated and real-world data sets.}, } @article {pmid29589560, year = {2018}, author = {Al Kawam, A and Alshawaqfeh, M and Cai, JJ and Serpedin, E and Datta, A}, title = {Simulating variance heterogeneity in quantitative genome wide association studies.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 3}, pages = {72}, pmid = {29589560}, issn = {1471-2105}, support = {R21 AI126219/AI/NIAID NIH HHS/United States ; }, abstract = {BACKGROUND: Analyzing Variance heterogeneity in genome wide association studies (vGWAS) is an emerging approach for detecting genetic loci involved in gene-gene and gene-environment interactions. vGWAS analysis detects variability in phenotype values across genotypes, as opposed to typical GWAS analysis, which detects variations in the mean phenotype value.

RESULTS: A handful of vGWAS analysis methods have been recently introduced in the literature. However, very little work has been done for evaluating these methods. To enable the development of better vGWAS analysis methods, this work presents the first quantitative vGWAS simulation procedure. To that end, we describe the mathematical framework and algorithm for generating quantitative vGWAS phenotype data from genotype profiles. Our simulation model accounts for both haploid and diploid genotypes under different modes of dominance. Our model is also able to simulate any number of genetic loci causing mean and variance heterogeneity.

CONCLUSIONS: We demonstrate the utility of our simulation procedure through generating a variety of genetic loci types to evaluate common GWAS and vGWAS analysis methods. The results of this evaluation highlight the challenges current tools face in detecting GWAS and vGWAS loci.}, } @article {pmid29589559, year = {2018}, author = {Matlock, K and De Niz, C and Rahman, R and Ghosh, S and Pal, R}, title = {Investigation of model stacking for drug sensitivity prediction.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 3}, pages = {71}, pmid = {29589559}, issn = {1471-2105}, support = {R01 GM122084/GM/NIGMS NIH HHS/United States ; }, abstract = {BACKGROUND: A significant problem in precision medicine is the prediction of drug sensitivity for individual cancer cell lines. Predictive models such as Random Forests have shown promising performance while predicting from individual genomic features such as gene expressions. However, accessibility of various other forms of data types including information on multiple tested drugs necessitates the examination of designing predictive models incorporating the various data types.

RESULTS: We explore the predictive performance of model stacking and the effect of stacking on the predictive bias and squared error. In addition we discuss the analytical underpinnings supporting the advantages of stacking in reducing squared error and inherent bias of random forests in prediction of outliers. The framework is tested on a setup including gene expression, drug target, physical properties and drug response information for a set of drugs and cell lines.

CONCLUSION: The performance of individual and stacked models are compared. We note that stacking models built on two heterogeneous datasets provide superior performance to stacking different models built on the same dataset. It is also noted that stacking provides a noticeable reduction in the bias of our predictors when the dominant eigenvalue of the principle axis of variation in the residuals is significantly higher than the remaining eigenvalues.}, } @article {pmid29589558, year = {2018}, author = {Foroughi Pour, A and Dalton, LA}, title = {Heuristic algorithms for feature selection under Bayesian models with block-diagonal covariance structure.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 3}, pages = {70}, pmid = {29589558}, issn = {1471-2105}, abstract = {BACKGROUND: Many bioinformatics studies aim to identify markers, or features, that can be used to discriminate between distinct groups. In problems where strong individual markers are not available, or where interactions between gene products are of primary interest, it may be necessary to consider combinations of features as a marker family. To this end, recent work proposes a hierarchical Bayesian framework for feature selection that places a prior on the set of features we wish to select and on the label-conditioned feature distribution. While an analytical posterior under Gaussian models with block covariance structures is available, the optimal feature selection algorithm for this model remains intractable since it requires evaluating the posterior over the space of all possible covariance block structures and feature-block assignments. To address this computational barrier, in prior work we proposed a simple suboptimal algorithm, 2MNC-Robust, with robust performance across the space of block structures. Here, we present three new heuristic feature selection algorithms.

RESULTS: The proposed algorithms outperform 2MNC-Robust and many other popular feature selection algorithms on synthetic data. In addition, enrichment analysis on real breast cancer, colon cancer, and Leukemia data indicates they also output many of the genes and pathways linked to the cancers under study.

CONCLUSIONS: Bayesian feature selection is a promising framework for small-sample high-dimensional data, in particular biomarker discovery applications. When applied to cancer data these algorithms outputted many genes already shown to be involved in cancer as well as potentially new biomarkers. Furthermore, one of the proposed algorithms, SPM, outputs blocks of heavily correlated genes, particularly useful for studying gene interactions and gene networks.}, } @article {pmid29589557, year = {2018}, author = {Yoon, BJ and Qian, X and Kahveci, T and Pal, R}, title = {Selected research articles from the 2017 International Workshop on Computational Network Biology: Modeling, Analysis, and Control (CNB-MAC).}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 3}, pages = {69}, pmid = {29589557}, issn = {1471-2105}, } @article {pmid29589556, year = {2018}, author = {Katiyar, A and Mohanty, A and Hua, J and Chao, S and Lopes, R and Datta, A and Bittner, ML}, title = {A Bayesian approach to determine the composition of heterogeneous cancer tissue.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 3}, pages = {90}, pmid = {29589556}, issn = {1471-2105}, abstract = {BACKGROUND: Cancer Tissue Heterogeneity is an important consideration in cancer research as it can give insights into the causes and progression of cancer. It is known to play a significant role in cancer cell survival, growth and metastasis. Determining the compositional breakup of a heterogeneous cancer tissue can also help address the therapeutic challenges posed by heterogeneity. This necessitates a low cost, scalable algorithm to address the challenge of accurate estimation of the composition of a heterogeneous cancer tissue.

METHODS: In this paper, we propose an algorithm to tackle this problem by utilizing the data of accurate, but high cost, single cell line cell-by-cell observation methods in low cost aggregate observation method for heterogeneous cancer cell mixtures to obtain their composition in a Bayesian framework.

RESULTS: The algorithm is analyzed and validated using synthetic data and experimental data. The experimental data is obtained from mixtures of three separate human cancer cell lines, HCT116 (Colorectal carcinoma), A2058 (Melanoma) and SW480 (Colorectal carcinoma).

CONCLUSION: The algorithm provides a low cost framework to determine the composition of heterogeneous cancer tissue which is a crucial aspect in cancer research.}, } @article {pmid29589555, year = {2018}, author = {Ni, Y and Müller, P and Wei, L and Ji, Y}, title = {Bayesian graphical models for computational network biology.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 3}, pages = {63}, pmid = {29589555}, issn = {1471-2105}, support = {R01 CA132897/CA/NCI NIH HHS/United States ; }, abstract = {BACKGROUND: Computational network biology is an emerging interdisciplinary research area. Among many other network approaches, probabilistic graphical models provide a comprehensive probabilistic characterization of interaction patterns between molecules and the associated uncertainties.

RESULTS: In this article, we first review graphical models, including directed, undirected, and reciprocal graphs (RG), with an emphasis on the RG models that are curiously under-utilized in biostatistics and bioinformatics literature. RG's strictly contain chain graphs as a special case and are suitable to model reciprocal causality such as feedback mechanism in molecular networks. We then extend the RG approach to modeling molecular networks by integrating DNA-, RNA- and protein-level data. We apply the extended RG method to The Cancer Genome Atlas multi-platform ovarian cancer data and reveal several interesting findings.

CONCLUSIONS: This study aims to review the basics of different probabilistic graphical models as well as recent development in RG approaches for network modeling. The extension presented in this paper provides a principled and efficient way of integrating DNA copy number, DNA methylation, mRNA gene expression and protein expression.}, } @article {pmid29589554, year = {2018}, author = {Hashemi, A and Zhu, B and Vikalo, H}, title = {Sparse Tensor Decomposition for Haplotype Assembly of Diploids and Polyploids.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 4}, pages = {191}, pmid = {29589554}, issn = {1471-2164}, mesh = {*Algorithms ; *Diploidy ; *Genome, Human ; *Haplotypes ; Humans ; Models, Genetic ; Phenotype ; Polymorphism, Single Nucleotide ; *Polyploidy ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Haplotype assembly is the task of reconstructing haplotypes of an individual from a mixture of sequenced chromosome fragments. Haplotype information enables studies of the effects of genetic variations on an organism's phenotype. Most of the mathematical formulations of haplotype assembly are known to be NP-hard and haplotype assembly becomes even more challenging as the sequencing technology advances and the length of the paired-end reads and inserts increases. Assembly of haplotypes polyploid organisms is considerably more difficult than in the case of diploids. Hence, scalable and accurate schemes with provable performance are desired for haplotype assembly of both diploid and polyploid organisms.

RESULTS: We propose a framework that formulates haplotype assembly from sequencing data as a sparse tensor decomposition. We cast the problem as that of decomposing a tensor having special structural constraints and missing a large fraction of its entries into a product of two factors, U and [Formula: see text]; tensor [Formula: see text] reveals haplotype information while U is a sparse matrix encoding the origin of erroneous sequencing reads. An algorithm, AltHap, which reconstructs haplotypes of either diploid or polyploid organisms by iteratively solving this decomposition problem is proposed. The performance and convergence properties of AltHap are theoretically analyzed and, in doing so, guarantees on the achievable minimum error correction scores and correct phasing rate are established. The developed framework is applicable to diploid, biallelic and polyallelic polyploid species. The code for AltHap is freely available from https://github.com/realabolfazl/AltHap .

CONCLUSION: AltHap was tested in a number of different scenarios and was shown to compare favorably to state-of-the-art methods in applications to haplotype assembly of diploids, and significantly outperforms existing techniques when applied to haplotype assembly of polyploids.}, } @article {pmid29588855, year = {2018}, author = {Chan, BK and Turner, PE and Kim, S and Mojibian, HR and Elefteriades, JA and Narayan, D}, title = {Phage treatment of an aortic graft infected with Pseudomonas aeruginosa.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {60-66}, pmid = {29588855}, issn = {2050-6201}, abstract = {Management of prosthetic vascular graft infections caused by Pseudomonas aeruginosa can be a significant challenge to clinicians. These infections often do not resolve with antibiotic therapy alone due to antibiotic resistance/tolerance by bacteria, poor ability of antibiotics to permeate/reduce biofilms and/or other factors. Bacteriophage OMKO1 binding to efflux pump proteins in P. aeruginosa was consistent with an evolutionary trade-off: wildtype bacteria were killed by phage whereas evolution of phage-resistance led to increased antibiotic sensitivity. However, phage clinical-use has not been demonstrated. Here, we present a case report detailing therapeutic application of phage OMKO1 to treat a chronic P. aeruginosa infection of an aortic Dacron graft with associated aorto-cutaneous fistula. Following a single application of phage OMKO1 and ceftazidime, the infection appeared to resolve with no signs of recurrence.}, } @article {pmid29588542, year = {2018}, author = {Zhu, D and Pan, C and Sheng, J and Liang, H and Bian, Z and Liu, Y and Trang, P and Wu, J and Liu, F and Zhang, CY and Zen, K}, title = {Human cytomegalovirus reprogrammes haematopoietic progenitor cells into immunosuppressive monocytes to achieve latency.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {503-513}, doi = {10.1038/s41564-018-0131-9}, pmid = {29588542}, issn = {2058-5276}, support = {R01 AI041927/AI/NIAID NIH HHS/United States ; R01 AI050468/AI/NIAID NIH HHS/United States ; R01 DE023935/DE/NIDCR NIH HHS/United States ; R01 DE025462/DE/NIDCR NIH HHS/United States ; }, abstract = {The precise cell type hosting latent human cytomegalovirus (HCMV) remains elusive. Here, we report that HCMV reprogrammes human haematopoietic progenitor cells (HPCs) into a unique monocyte subset to achieve latency. Unlike conventional monocytes, this monocyte subset possesses higher levels of B7-H4, IL-10 and inducible nitric oxide synthase (iNOS), a longer lifespan and strong immunosuppressive capacity. Cell sorting of peripheral blood from latently infected human donors confirms that only this monocyte subset, representing less than 0.1% of peripheral mononuclear cells, is HCMV genome-positive but immediate-early-negative. Mechanistic studies demonstrate that HCMV promotes the differentiation of HPCs into this monocyte subset by activating cellular signal transducer and activator of transcription 3 (STAT3). In turn, this monocyte subset generates a high level of nitric oxide (NO) to silence HCMV immediate-early transcription and promote viral latency. By contrast, the US28-knockout HCMV mutant, which is incapable of activating STAT3, fails to reprogramme the HPCs and achieve latency. Our findings reveal that via activating the STAT3-iNOS-NO axis, HCMV differentiates human HPCs into a longevous, immunosuppressive monocyte subset for viral latency.}, } @article {pmid29588541, year = {2018}, author = {Brown, NA and Schrevens, S and van Dijck, P and Goldman, GH}, title = {Fungal G-protein-coupled receptors: mediators of pathogenesis and targets for disease control.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {402-414}, doi = {10.1038/s41564-018-0127-5}, pmid = {29588541}, issn = {2058-5276}, abstract = {G-protein signalling pathways are involved in sensing the environment, enabling fungi to coordinate cell function, metabolism and development with their surroundings, thereby promoting their survival, propagation and virulence. G-protein-coupled receptors (GPCRs) are the largest class of cell surface receptors in fungi. Despite the apparent importance of GPCR signalling to fungal biology and virulence, relatively few GPCR-G-protein interactions, and even fewer receptor-binding ligands, have been identified. Approximately 40% of current pharmaceuticals target human GPCRs, due to their cell surface location and central role in cell signalling. Fungal GPCRs do not belong to any of the mammalian receptor classes, making them druggable targets for antifungal development. This Review Article evaluates developments in our understanding of fungal GPCR-mediated signalling, while substantiating the rationale for considering these receptors as potential antifungal targets. The need for insights into the structure-function relationship of receptor-ligand interactions is highlighted, which could facilitate the development of receptor-interfering compounds that could be used in disease control.}, } @article {pmid29588540, year = {2018}, author = {}, title = {Viruses are models for embracing diversity.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {389}, doi = {10.1038/s41564-018-0145-3}, pmid = {29588540}, issn = {2058-5276}, } @article {pmid29588539, year = {2018}, author = {Beattie, GA}, title = {Metabolic coupling on roots.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {396-397}, doi = {10.1038/s41564-018-0139-1}, pmid = {29588539}, issn = {2058-5276}, } @article {pmid29588538, year = {2018}, author = {Crofts, AA and Poly, FM and Ewing, CP and Kuroiwa, JM and Rimmer, JE and Harro, C and Sack, D and Talaat, KR and Porter, CK and Gutierrez, RL and DeNearing, B and Brubaker, J and Laird, RM and Maue, AC and Jaep, K and Alcala, A and Tribble, DR and Riddle, MS and Ramakrishnan, A and McCoy, AJ and Davies, BW and Guerry, P and Trent, MS}, title = {Campylobacter jejuni transcriptional and genetic adaptation during human infection.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {494-502}, pmid = {29588538}, issn = {2058-5276}, support = {R01 AI064184/AI/NIAID NIH HHS/United States ; R01 AI076322/AI/NIAID NIH HHS/United States ; R01 AI129940/AI/NIAID NIH HHS/United States ; }, abstract = {Campylobacter jejuni infections are a leading cause of bacterial food-borne diarrhoeal illness worldwide, and Campylobacter infections in children are associated with stunted growth and therefore long-term deficits into adulthood. Despite this global impact on health and human capital, how zoonotic C. jejuni responds to the human host remains unclear. Unlike other intestinal pathogens, C. jejuni does not harbour pathogen-defining toxins that explicitly contribute to disease in humans. This makes understanding Campylobacter pathogenesis challenging and supports a broad examination of bacterial factors that contribute to C. jejuni infection. Here, we use a controlled human infection model to characterize C. jejuni transcriptional and genetic adaptations in vivo, along with a non-human primate infection model to validate our approach. We found that variation in 11 genes is associated with either acute or persistent human infections and includes products involved in host cell invasion, bile sensing and flagella modification, plus additional potential therapeutic targets. In particular, a functional version of the cell invasion protein A (cipA) gene product is strongly associated with persistently infecting bacteria and we identified its biochemical role in flagella modification. These data characterize the adaptive C. jejuni response to primate infections and suggest therapy design should consider the intrinsic differences between acute and persistently infecting bacteria. In addition, RNA sequencing revealed conserved responses during natural host commensalism and human infections. Thirty-nine genes were differentially regulated in vivo across hosts, lifestyles and C. jejuni strains. This conserved in vivo response highlights important C. jejuni survival mechanisms such as iron acquisition and evasion of the host mucosal immune response. These advances highlight pathogen adaptability across host species and demonstrate the utility of multidisciplinary collaborations in future clinical trials to study pathogens in vivo.}, } @article {pmid29588537, year = {2018}, author = {Reeves, MB}, title = {Viral programming of progenitor cell commitment.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {398-399}, doi = {10.1038/s41564-018-0136-4}, pmid = {29588537}, issn = {2058-5276}, } @article {pmid29588536, year = {2018}, author = {Bleves, S and Berni, B}, title = {United we stand and divided we fall.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {394-395}, doi = {10.1038/s41564-018-0130-x}, pmid = {29588536}, issn = {2058-5276}, } @article {pmid29588535, year = {2018}, author = {Miller, CL}, title = {The TRiCky business of reovirus assembly.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {400-401}, doi = {10.1038/s41564-018-0137-3}, pmid = {29588535}, issn = {2058-5276}, } @article {pmid29588534, year = {2018}, author = {Lam, YC and Crawford, JM}, title = {Discovering antibiotics from the global microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {392-393}, doi = {10.1038/s41564-018-0135-5}, pmid = {29588534}, issn = {2058-5276}, } @article {pmid29588533, year = {2018}, author = {Pariente, N}, title = {The quest for quasispecies.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {390-391}, doi = {10.1038/s41564-018-0140-8}, pmid = {29588533}, issn = {2058-5276}, abstract = {This month marks 40 years since the publication of 'Nucleotide sequence heterogeneity of an RNA phage population' in Cell. We spoke with Esteban Domingo, leading author of this landmark study carried out during his postdoctoral work in Charles Weissman's lab, which proposed RNA viral populations to be quasispecies.}, } @article {pmid29588424, year = {2018}, author = {Beans, C}, title = {News Feature: What happens when lab animals go wild.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3196-3199}, pmid = {29588424}, issn = {1091-6490}, mesh = {Animal Husbandry/methods ; Animals ; Animals, Laboratory ; *Disease Models, Animal ; Female ; Humans ; Laboratory Animal Science/*methods ; Male ; Mice ; Mice, Inbred Strains ; }, } @article {pmid29588421, year = {2018}, author = {Alvarez, MI and Ko, DC}, title = {Reply to Gilchrist et al.: Possible roles for VAC14 in multiple infectious diseases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3604-E3605}, pmid = {29588421}, issn = {1091-6490}, support = {R01 AI118903/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteremia ; *Communicable Diseases ; Humans ; Membrane Proteins ; Salmonella Infections ; Typhoid Fever ; }, } @article {pmid29588420, year = {2018}, author = {Le, DD and Shimko, TC and Aditham, AK and Keys, AM and Longwell, SA and Orenstein, Y and Fordyce, PM}, title = {Comprehensive, high-resolution binding energy landscapes reveal context dependencies of transcription factor binding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3702-E3711}, pmid = {29588420}, issn = {1091-6490}, support = {R00 GM099848/GM/NIGMS NIH HHS/United States ; }, mesh = {Base Sequence ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism ; Binding Sites ; Computer Simulation ; DNA/*metabolism ; DNA-Binding Proteins/metabolism ; E-Box Elements ; Gene Library ; High-Throughput Nucleotide Sequencing/*methods ; Microfluidic Analytical Techniques ; Monte Carlo Method ; Protein Binding ; Saccharomyces cerevisiae Proteins/metabolism ; Sequence Analysis, DNA ; Thermodynamics ; Transcription Factors/*metabolism ; Transcription, Genetic ; }, abstract = {Transcription factors (TFs) are primary regulators of gene expression in cells, where they bind specific genomic target sites to control transcription. Quantitative measurements of TF-DNA binding energies can improve the accuracy of predictions of TF occupancy and downstream gene expression in vivo and shed light on how transcriptional networks are rewired throughout evolution. Here, we present a sequencing-based TF binding assay and analysis pipeline (BET-seq, for Binding Energy Topography by sequencing) capable of providing quantitative estimates of binding energies for more than one million DNA sequences in parallel at high energetic resolution. Using this platform, we measured the binding energies associated with all possible combinations of 10 nucleotides flanking the known consensus DNA target interacting with two model yeast TFs, Pho4 and Cbf1. A large fraction of these flanking mutations change overall binding energies by an amount equal to or greater than consensus site mutations, suggesting that current definitions of TF binding sites may be too restrictive. By systematically comparing estimates of binding energies output by deep neural networks (NNs) and biophysical models trained on these data, we establish that dinucleotide (DN) specificities are sufficient to explain essentially all variance in observed binding behavior, with Cbf1 binding exhibiting significantly more nonadditivity than Pho4. NN-derived binding energies agree with orthogonal biochemical measurements and reveal that dynamically occupied sites in vivo are both energetically and mutationally distant from the highest affinity sites.}, } @article {pmid29588419, year = {2018}, author = {Martin-Sanchez, D and Fontecha-Barriuso, M and Carrasco, S and Sanchez-Niño, MD and Mässenhausen, AV and Linkermann, A and Cannata-Ortiz, P and Ruiz-Ortega, M and Egido, J and Ortiz, A and Sanz, AB}, title = {TWEAK and RIPK1 mediate a second wave of cell death during AKI.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4182-4187}, pmid = {29588419}, issn = {1091-6490}, mesh = {Acute Kidney Injury/chemically induced/*pathology ; Animals ; Apoptosis/drug effects ; Cell Line ; Cellular Microenvironment ; Cytokine TWEAK/*physiology ; Enzyme Activation ; Female ; Folic Acid/toxicity ; Imidazoles/pharmacology ; Indoles/pharmacology ; Inflammation ; Kidney Tubules, Proximal/cytology/drug effects ; Mice ; Mice, Inbred C57BL ; Necrosis ; Receptor-Interacting Protein Serine-Threonine Kinases/biosynthesis/deficiency/genetics/*physiology ; TWEAK Receptor/biosynthesis/genetics/*physiology ; }, abstract = {Acute kidney injury (AKI) is characterized by necrotic tubular cell death and inflammation. The TWEAK/Fn14 axis is a mediator of renal injury. Diverse pathways of regulated necrosis have recently been reported to contribute to AKI, but there are ongoing discussions on the timing or molecular regulators involved. We have now explored the cell death pathways induced by TWEAK/Fn14 activation and their relevance during AKI. In cultured tubular cells, the inflammatory cytokine TWEAK induces apoptosis in a proinflammatory environment. The default inhibitor of necroptosis [necrostatin-1 (Nec-1)] was protective, while caspase inhibition switched cell death to necroptosis. Additionally, folic acid-induced AKI in mice resulted in increased expression of Fn14 and necroptosis mediators, such as receptor-interacting protein kinase 1 (RIPK1), RIPK3, and mixed lineage domain-like protein (MLKL). Targeting necroptosis with Nec-1 or by genetic RIPK3 deficiency and genetic Fn14 ablation failed to be protective at early time points (48 h). However, a persistently high cell death rate and kidney dysfunction (72-96 h) were dependent on an intact TWEAK/Fn14 axis driving necroptosis. This was prevented by Nec-1, or MLKL, or RIPK3 deficiency and by Nec-1 stable (Nec-1s) administered before or after induction of AKI. These data suggest that initial kidney damage and cell death are amplified through recruitment of inflammation-dependent necroptosis, opening a therapeutic window to treat AKI once it is established. This may be relevant for clinical AKI, since using current diagnostic criteria, severe injury had already led to loss of renal function at diagnosis.}, } @article {pmid29588418, year = {2018}, author = {Yanez Arteta, M and Kjellman, T and Bartesaghi, S and Wallin, S and Wu, X and Kvist, AJ and Dabkowska, A and Székely, N and Radulescu, A and Bergenholtz, J and Lindfors, L}, title = {Successful reprogramming of cellular protein production through mRNA delivered by functionalized lipid nanoparticles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3351-E3360}, pmid = {29588418}, issn = {1091-6490}, mesh = {Adipocytes/metabolism ; Drug Delivery Systems/instrumentation/*methods ; Erythropoietin/*genetics/metabolism ; Hepatocytes/*metabolism ; Humans ; Lipids/*chemistry ; Nanoparticles/*chemistry ; Particle Size ; RNA, Messenger/chemistry/*genetics/metabolism ; Transfection ; }, abstract = {The development of safe and efficacious gene vectors has limited greatly the potential for therapeutic treatments based on messenger RNA (mRNA). Lipid nanoparticles (LNPs) formed by an ionizable cationic lipid (here DLin-MC3-DMA), helper lipids (distearoylphosphatidylcholine, DSPC, and cholesterol), and a poly(ethylene glycol) (PEG) lipid have been identified as very promising delivery vectors of short interfering RNA (siRNA) in different clinical phases; however, delivery of high-molecular weight RNA has been proven much more demanding. Herein we elucidate the structure of hEPO modified mRNA-containing LNPs of different sizes and show how structural differences affect transfection of human adipocytes and hepatocytes, two clinically relevant cell types. Employing small-angle scattering, we demonstrate that LNPs have a disordered inverse hexagonal internal structure with a characteristic distance around 6 nm in presence of mRNA, whereas LNPs containing no mRNA do not display this structure. Furthermore, using contrast variation small-angle neutron scattering, we show that one of the lipid components, DSPC, is localized mainly at the surface of mRNA-containing LNPs. By varying LNP size and surface composition we demonstrate that both size and structure have significant influence on intracellular protein production. As an example, in both human adipocytes and hepatocytes, protein expression levels for 130 nm LNPs can differ as much as 50-fold depending on their surface characteristics, likely due to a difference in the ability of LNP fusion with the early endosome membrane. We consider these discoveries to be fundamental and opening up new possibilities for rational design of synthetic nanoscopic vehicles for mRNA delivery.}, } @article {pmid29588417, year = {2018}, author = {Blau, SM and Bennett, DIG and Kreisbeck, C and Scholes, GD and Aspuru-Guzik, A}, title = {Local protein solvation drives direct down-conversion in phycobiliprotein PC645 via incoherent vibronic transport.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3342-E3350}, pmid = {29588417}, issn = {1091-6490}, mesh = {Energy Transfer ; Fluorescence ; Light ; Light-Harvesting Protein Complexes/*chemistry/metabolism ; Molecular Dynamics Simulation ; Photosynthesis ; Phycobiliproteins/*chemistry/metabolism ; Pigments, Biological/chemistry/metabolism ; Quantum Theory ; Vibration ; }, abstract = {The mechanisms controlling excitation energy transport (EET) in light-harvesting complexes remain controversial. Following the observation of long-lived beats in 2D electronic spectroscopy of PC645, vibronic coherence, the delocalization of excited states between pigments supported by a resonant vibration, has been proposed to enable direct excitation transport from the highest-energy to the lowest-energy pigments, bypassing a collection of intermediate states. Here, we instead show that for phycobiliprotein PC645 an incoherent vibronic transport mechanism is at play. We quantify the solvation dynamics of individual pigments using ab initio quantum mechanics/molecular mechanics (QM/MM) nuclear dynamics. Our atomistic spectral densities reproduce experimental observations ranging from absorption and fluorescence spectra to the timescales and selectivity of down-conversion observed in transient absorption measurements. We construct a general model for vibronic dimers and establish the parameter regimes of coherent and incoherent vibronic transport. We demonstrate that direct down-conversion in PC645 proceeds incoherently, enhanced by large reorganization energies and a broad collection of high-frequency vibrations. We suggest that a similar incoherent mechanism is appropriate across phycobiliproteins and represents a potential design principle for nanoscale control of EET.}, } @article {pmid29588416, year = {2018}, author = {Lee, SH and Seo, J and Park, SY and Jeong, MH and Choi, HK and Lee, CJ and Kim, MJ and Guk, G and Lee, S and Park, H and Jeong, JW and Ha, CH and Park, S and Yoon, HG}, title = {Programmed cell death 5 suppresses AKT-mediated cytoprotection of endothelium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {4672-4677}, pmid = {29588416}, issn = {1091-6490}, mesh = {Animals ; Apoptosis Regulatory Proteins/genetics/*metabolism ; Atherosclerosis/genetics/metabolism/pathology ; Cholesterol, HDL/genetics/metabolism ; Diabetes Mellitus/genetics/metabolism/pathology ; Endothelium, Vascular/*metabolism/pathology ; Histone Deacetylases/genetics/metabolism ; Human Umbilical Vein Endothelial Cells/*metabolism/pathology ; Humans ; Mice ; Mice, Knockout ; Neoplasm Proteins/genetics/*metabolism ; Nitric Oxide Synthase Type III/genetics/metabolism ; Phosphorylation/genetics ; Proto-Oncogene Proteins c-akt/genetics/*metabolism ; *Vascular Remodeling ; }, abstract = {Programmed cell death 5 (PDCD5) has been associated with human cancers as a regulator of cell death; however, the role of PDCD5 in the endothelium has not been revealed. Thus, we investigated whether PDCD5 regulates protein kinase B (PKB/AKT)-endothelial nitric oxide synthase (eNOS)-dependent signal transduction in the endothelium and affects atherosclerosis. Endothelial-specific PDCD5 knockout mice showed significantly reduced vascular remodeling compared with wild-type (WT) mice after partial carotid ligation. WT PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT, but PDCD5L6R, an HDAC3-binding-deficient mutant, did not. Knockdown of PDCD5 accelerated HDAC3-AKT interaction, AKT and eNOS phosphorylation, and nitric oxide (NO) production in human umbilical vein endothelial cells. Moreover, we found that serum PDCD5 levels reflect endothelial NO production and are correlated with diabetes mellitus, high-density lipoprotein cholesterol, and coronary calcium in human samples obtained from the cardiovascular high-risk cohort. Therefore, we conclude that PDCD5 is associated with endothelial dysfunction and may be a novel therapeutic target in atherosclerosis.}, } @article {pmid29588415, year = {2018}, author = {Safavi, S and Dwarakanath, A and Kapoor, V and Werner, J and Hatsopoulos, NG and Logothetis, NK and Panagiotaropoulos, TI}, title = {Nonmonotonic spatial structure of interneuronal correlations in prefrontal microcircuits.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3539-E3548}, pmid = {29588415}, issn = {1091-6490}, mesh = {Action Potentials/physiology ; Animals ; Connectome/methods ; Interneurons ; Macaca ; Male ; Nerve Net/physiology ; Neural Pathways/*physiology ; Neurons/physiology ; Photic Stimulation ; Prefrontal Cortex/anatomy & histology/*physiology ; Spatial Analysis ; Structure-Activity Relationship ; Visual Cortex/anatomy & histology/physiology ; Wakefulness ; }, abstract = {Correlated fluctuations of single neuron discharges, on a mesoscopic scale, decrease as a function of lateral distance in early sensory cortices, reflecting a rapid spatial decay of lateral connection probability and excitation. However, spatial periodicities in horizontal connectivity and associational input as well as an enhanced probability of lateral excitatory connections in the association cortex could theoretically result in nonmonotonic correlation structures. Here, we show such a spatially nonmonotonic correlation structure, characterized by significantly positive long-range correlations, in the inferior convexity of the macaque prefrontal cortex. This functional connectivity kernel was more pronounced during wakefulness than anesthesia and could be largely attributed to the spatial pattern of correlated variability between functionally similar neurons during structured visual stimulation. These results suggest that the spatial decay of lateral functional connectivity is not a common organizational principle of neocortical microcircuits. A nonmonotonic correlation structure could reflect a critical topological feature of prefrontal microcircuits, facilitating their role in integrative processes.}, } @article {pmid29588414, year = {2018}, author = {Gilchrist, JJ and Mentzer, AJ and Rautanen, A and Pirinen, M and Mwarumba, S and Njuguna, P and Mturi, N and , and , and Williams, TN and Scott, JAG and Hill, AVS}, title = {Genetic variation in VAC14 is associated with bacteremia secondary to diverse pathogens in African children.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {E3601-E3603}, pmid = {29588414}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {*Bacteremia ; Child ; *Genetic Variation ; Humans ; Membrane Proteins/genetics ; }, } @article {pmid29588109, year = {2018}, author = {Wang, CY and Dawid, S}, title = {Mobilization of Bacteriocins during Competence in Streptococci.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {389-391}, pmid = {29588109}, issn = {1878-4380}, support = {R01 AI101285/AI/NIAID NIH HHS/United States ; T32 GM007863/GM/NIGMS NIH HHS/United States ; }, mesh = {*Bacteriocins ; Streptococcus ; *Streptococcus salivarius ; }, abstract = {Many streptococci have evolved the ability for natural genetic competence. Recent studies have uncovered regulatory links between competence and the production of antimicrobial peptides called bacteriocins in multiple streptococcal species. This reveals a broadly distributed strategy among streptococci to exploit bacteriocin-mediated killing during competence for adaptive gain.}, } @article {pmid29588071, year = {2018}, author = {Struck, TH and Feder, JL and Bendiksby, M and Birkeland, S and Cerca, J and Gusarov, VI and Kistenich, S and Larsson, KH and Liow, LH and Nowak, MD and Stedje, B and Bachmann, L and Dimitrov, D}, title = {Cryptic Species - More Than Terminological Chaos: A Reply to Heethoff.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {310-312}, doi = {10.1016/j.tree.2018.02.008}, pmid = {29588071}, issn = {1872-8383}, mesh = {Biodiversity ; *Genetic Speciation ; Genetic Variation ; *Phylogeny ; }, } @article {pmid29587885, year = {2018}, author = {Hassani, MA and Durán, P and Hacquard, S}, title = {Microbial interactions within the plant holobiont.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {58}, pmid = {29587885}, issn = {2049-2618}, support = {758003//European Research Council/International ; }, mesh = {Bacteria/classification ; Biodiversity ; Biological Evolution ; Fungi/classification ; Microbial Consortia ; *Microbial Interactions ; *Microbiota ; Plant Development ; Plants/*microbiology ; }, abstract = {Since the colonization of land by ancestral plant lineages 450 million years ago, plants and their associated microbes have been interacting with each other, forming an assemblage of species that is often referred to as a "holobiont." Selective pressure acting on holobiont components has likely shaped plant-associated microbial communities and selected for host-adapted microorganisms that impact plant fitness. However, the high microbial densities detected on plant tissues, together with the fast generation time of microbes and their more ancient origin compared to their host, suggest that microbe-microbe interactions are also important selective forces sculpting complex microbial assemblages in the phyllosphere, rhizosphere, and plant endosphere compartments. Reductionist approaches conducted under laboratory conditions have been critical to decipher the strategies used by specific microbes to cooperate and compete within or outside plant tissues. Nonetheless, our understanding of these microbial interactions in shaping more complex plant-associated microbial communities, along with their relevance for host health in a more natural context, remains sparse. Using examples obtained from reductionist and community-level approaches, we discuss the fundamental role of microbe-microbe interactions (prokaryotes and micro-eukaryotes) for microbial community structure and plant health. We provide a conceptual framework illustrating that interactions among microbiota members are critical for the establishment and the maintenance of host-microbial homeostasis.}, } @article {pmid29587880, year = {2018}, author = {Gasc, C and Peyret, P}, title = {Hybridization capture reveals microbial diversity missed using current profiling methods.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {61}, pmid = {29587880}, issn = {2049-2618}, mesh = {Archaea/classification/genetics ; Bacteria/classification/genetics ; *Biodiversity ; *Metagenome ; *Metagenomics/methods ; *Nucleic Acid Hybridization ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Reproducibility of Results ; Soil Microbiology ; }, abstract = {BACKGROUND: Microorganisms comprise the majority of living organisms on our planet. For many years, exploration of the composition of microbial communities has been performed through the PCR-based study of the small subunit rRNA gene due to its high conservation across the domains of life. The application of this method has resulted in the discovery of many unexpected evolutionary lineages. However, amplicon sequencing is subject to numerous biases, with some taxa being missed, and is limited by the read length of second-generation sequencing platforms, which drastically reduces the phylogenetic resolution.

RESULTS: Here, we describe a hybridization capture strategy that allows the enrichment of 16S rRNA genes from metagenomic samples and enables an exhaustive identification and a complete reconstruction of the biomarker. Applying this approach to a microbial mock community and a soil sample, we demonstrated that hybridization capture is able to reveal greater microbial diversity than 16S rDNA amplicon sequencing and shotgun sequencing. The reconstruction of full-length 16S rRNA genes facilitated the improvement of phylogenetic resolution and the discovery of novel prokaryotic taxa.

CONCLUSIONS: Our results demonstrate that hybridization capture can lead to major breakthroughs in our understanding of microbial diversity, overcoming the limitations of conventional 16S rRNA gene studies. If applied to a broad range of environmental samples, this innovative approach could reveal the undescribed diversity of the still underexplored microbial communities and could provide a better understanding of ecosystem function.}, } @article {pmid29587868, year = {2018}, author = {Haste, A and Adamson, AJ and McColl, E and Araujo-Soares, V and Bell, R}, title = {Problems recruiting and retaining postnatal women to a pilot randomised controlled trial of a web-delivered weight loss intervention.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {203}, pmid = {29587868}, issn = {1756-0500}, support = {ES/G007470/1//Economic and Social Research Council (GB)/ ; }, mesh = {Adult ; Feasibility Studies ; Female ; Humans ; *Internet ; Overweight/prevention & control ; Patient Acceptance of Health Care/statistics & numerical data ; *Patient Selection ; Pilot Projects ; Postpartum Period ; Randomized Controlled Trials as Topic/*methods ; Weight Reduction Programs/*methods ; }, abstract = {OBJECTIVE: This paper highlights recruitment and retention problems identified during a pilot randomised controlled trial and process evaluation. The pilot trial aimed to evaluate the feasibility and acceptability of a web-delivered weight loss intervention for postnatal women and associated trial protocol.

RESULTS: General practice database searches revealed low rates of eligible postnatal women per practice. 16 (10%) of the 168 identified women were recruited and randomised, seven to the intervention and nine to the control. 57% (4/7) of the intervention women completed 3 month follow-up measurements in comparison to 56% (5/9) in the control group. By 12 months, retention in the intervention group was 43% (3/7), with 2/7 women active on the website, in comparison to 44% (4/9) of the control group. Interview findings revealed the web as an acceptable method for delivery of the intervention, with the suggestion of an addition of a mobile application. Alternative recruitment strategies, using health visitor appointments, midwifery departments or mother and baby/toddler groups, should be explored. Greater involvement of potential users should enable better recruitment methods to be developed. Trial registration ISRCTN: ISRCTN48086713, Registered 26 October 2012.}, } @article {pmid29587859, year = {2018}, author = {Yurco, P and Keeney, DB}, title = {Characterization of tri and tetra-nucleotide microsatellite loci for the freshwater snails Promenetus exacuous (Planorbidae) and Valvata tricarinata (Valvatidae) and their utility in population genetic studies.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {204}, pmid = {29587859}, issn = {1756-0500}, mesh = {Alleles ; Animals ; Fresh Water ; *Genetic Variation ; Genetics, Population ; Heterozygote ; High-Throughput Nucleotide Sequencing/*methods ; Lakes ; Microsatellite Repeats/*genetics ; New York ; Snails/classification/*genetics ; Species Specificity ; }, abstract = {OBJECTIVE: Promenetus exacuous and Valvata tricarinata are freshwater snail species with widespread distributions throughout North America. Information regarding their genetic diversity and population connectivity are currently lacking. We utilized next generation sequencing to develop the first microsatellites for each species to investigate genetic diversity within and differentiation among populations.

RESULTS: Sixteen and seventeen microsatellite loci were developed for P. exacuous and V. tricarinata, respectively, and tested in a total of 43 P. exacuous and 48 V. tricarinata from two lakes approximately 183 km apart in New York State, USA. Fifteen P. exacuous loci were polymorphic in at least one lake and possessed 1-23 alleles and observed heterozygosities of 0.00-0.96 within individual lakes. Seventeen polymorphic V. tricarinata loci possessed 2-19 alleles and observed heterozygosities of 0.04-0.96 within lakes. Bayesian clustering using 12 loci for each species identified two distinct genetic populations, reflecting the two lakes. High assignment scores for individual snails to the lakes they were collected from supported strong population structure with minimal admixture at the scale of this study. These loci will be useful for investigating the genetic diversity and population structure of these species and indicate genetic differentiation may be common among their populations.}, } @article {pmid29587855, year = {2018}, author = {Zhou, M and Peng, YJ and Chen, Y and Klinger, CM and Oba, M and Liu, JX and Guan, LL}, title = {Assessment of microbiome changes after rumen transfaunation: implications on improving feed efficiency in beef cattle.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {62}, pmid = {29587855}, issn = {2049-2618}, support = {2010R024R//Alberta Livestock and Meat Agency/International ; ABP0009-036//Alberta Beef Producer/International ; Discovery//National Science Engineering Research Council/International ; }, mesh = {Animal Feed ; Animals ; Archaea/classification/genetics ; Bacteria/classification/genetics ; Cattle ; Fermentation ; High-Throughput Nucleotide Sequencing ; *Microbiota ; Rumen/*microbiology ; }, abstract = {BACKGROUND: Understanding the host impact on its symbiotic microbiota is important in redirecting the rumen microbiota and thus improving animal performance. The current study aimed to understand how rumen microbiota were altered and re-established after being emptied and receiving content from donor, thus to understand the impact of such process on rumen microbial fermentation and to explore the microbial phylotypes with higher manipulation potentials.

RESULTS: Individual animal had strong effect on the re-establishment of the bacterial community according to the observed profiles detected by both fingerprinting and pyrosequencing. Most of the bacterial profile recovery patterns and extents at genus level varied among steers; and each identified bacterial genus responded to transfaunation differently within each host. Coriobacteriaceae, Coprococcus, and Lactobacillus were found to be the most responsive and tunable genera by exchanging rumen content. Besides, the association of 18 bacterial phylotypes with host fermentation parameters suggest that these phylotypes should also be considered as the regulating targets in improving host feed efficiency. In addition, the archaeal community had different re-establishment patterns for each host as determined by fingerprint profiling: it was altered after receiving non-native microbiome in some animals, while it resumed its original status after the adaptation period in the other ones.

CONCLUSIONS: The highly individualized microbial re-establishment process suggested the importance of considering host genetics, microbial functional genomics, and host fermentation/performance assessment when developing effective and selective microbial manipulation methods for improving animal feed efficiency.}, } @article {pmid29587848, year = {2018}, author = {Hashmi, AA and Hussain, ZF and Irfan, M and Edhi, MM and Kanwal, S and Faridi, N and Khan, A}, title = {Cytokeratin 5/6 expression in bladder cancer: association with clinicopathologic parameters and prognosis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {207}, pmid = {29587848}, issn = {1756-0500}, mesh = {Adult ; Aged ; Biomarkers, Tumor/biosynthesis ; Carcinoma, Transitional Cell/*metabolism/mortality/pathology ; Female ; Humans ; Immunohistochemistry ; Kaplan-Meier Estimate ; Keratin-5/*biosynthesis ; Keratin-6/*biosynthesis ; Male ; Middle Aged ; Prognosis ; Urinary Bladder Neoplasms/*metabolism/mortality/pathology ; }, abstract = {OBJECTIVES: Well differentiated keratinized squamous component as a part of urothelial carcinoma can be easily appreciated; however non-keratinizing squamous differentiation closely resembles urothelial differentiation. In addition prognostic significance of CK 5/6 expression in the absence of apparent squamous differentiation is still unclear. Therefore, in the present study we aimed to evaluate the frequency of CK 5/6 expression in 127 cases of urothelial carcinoma and its prognostic significance in loco-regional population.

RESULTS: Positive CK5/6 expression was noted in 6.3% (8 cases) and 13.4% (17 cases) revealed focal positive CK 5/6 expression. On the other hand, 80.3% (102 cases) showed negative CK5/6 staining. Significant association of CK5/6 expression was noted with tumor grade and muscularis propria invasion, however no significant association was noted with overall and disease free survival. On the basis of the results of our study we can conclude that CK5/6 is an independent prognostic biomarker in urothelial carcinoma and therefore can be used in the prognostic stratification of the patients with bladder cancer.}, } @article {pmid29587846, year = {2018}, author = {Menu, E and Mary, C and Toga, I and Raoult, D and Ranque, S and Bittar, F}, title = {Evaluation of two DNA extraction methods for the PCR-based detection of eukaryotic enteric pathogens in fecal samples.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {206}, pmid = {29587846}, issn = {1756-0500}, mesh = {Blastocystis/genetics/pathogenicity ; Cryptosporidium parvum/genetics/pathogenicity ; Cyclospora/genetics/pathogenicity ; DNA, Protozoan/genetics/*isolation & purification ; Eukaryota/classification/genetics/*pathogenicity ; Feces/*parasitology ; Giardia lamblia/genetics/pathogenicity ; Humans ; Microsporidia/genetics/pathogenicity ; Molecular Diagnostic Techniques/methods ; Polymerase Chain Reaction/*methods ; Protozoan Infections/*diagnosis/*parasitology ; Reproducibility of Results ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Efficient and easy-to-use DNA extraction and purification methods are critical in implementing PCR-based diagnosis of pathogens. In order to optimize the routine clinical laboratory diagnosis of eukaryotic enteric pathogens, we compare, via quantitative PCR cycle threshold (Ct) values, the efficiency of two DNA extraction kits: the semi-automated EZ1® (Qiagen) and the manual QIAamp® DNA Stool Mini Kit (Qiagen), on six protozoa: Blastocystis spp., Cryptosporidium parvum/hominis, Cyclospora cayetanensis, Dientamoeba fragilis, Giardia intestinalis and Cystoisospora belli and one microsporidia: Enterocytozoon bieneusi.

RESULTS: Whereas EZ1® (Qiagen) and QIAamp® DNA Stool Mini Kit (Qiagen) yielded similar performances for the detection of Cryptosporidium spp. and D. fragilis, significant lower Ct values (p < 0.002) pointed out a better performance of EZ1® on the five remaining pathogens. DNA extraction using the semi-automated EZ1® procedure was faster and as efficient as the manual procedure in the seven eukaryotic enteric pathogens tested. This procedure is suitable for DNA extraction from stools in both clinical laboratory diagnosis and epidemiological study settings.}, } @article {pmid29587845, year = {2018}, author = {Chin, RM and Panavas, T and Brown, JM and Johnson, KK}, title = {Patient-derived lymphoblastoid cell lines harboring mitochondrial DNA mutations as tool for small molecule drug discovery.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {205}, pmid = {29587845}, issn = {1756-0500}, mesh = {Adult ; Cell Line ; Child ; Child, Preschool ; DNA, Mitochondrial/*genetics ; Drug Discovery/*methods ; Female ; Humans ; Lymphocytes/drug effects/metabolism ; Male ; Mitochondrial Diseases/drug therapy/*genetics/pathology ; Oxygen Consumption/drug effects ; *Point Mutation ; Small Molecule Libraries/therapeutic use ; Ubiquinone/analogs & derivatives/therapeutic use ; Young Adult ; }, abstract = {OBJECTIVE: Mitochondrial diseases are a group of devastating disorders for which there is no transformative cure. The majority of therapies for mitochondrial disease-approved, previously tested, or currently in development-are small molecules. The implementation of better cell-based models of mitochondrial disease can accelerate and improve the accuracy of small molecule drug discovery. The objective of this study is to evaluate the use of patient-derived lymphoblastoid cell lines for small molecule research in mitochondrial disease.

RESULTS: Five lymphoblastoid cell lines derived from mitochondrial disease patients harboring point mutations in mtND1, mtND4, or mtATP6 were characterized in two high throughput assays assessing mitochondrial function. In a pilot "clinical trial in a dish" experiment, the efficacy of idebenone-an approved therapy for mitochondrial disease-on the lymphoblastoid cell lines was tested. Idebenone increased the basal respiration of all lymphoblastoid cell lines except those harboring the 8993T>G point mutation in mtATP6. Our results posit lymphoblastoid cell lines as a strong model for mitochondrial disease research with small molecules and have implications for the clinical efficacy of idebenone.}, } @article {pmid29587843, year = {2018}, author = {Buntragulpoontawee, M and Phutrit, S and Tongprasert, S and Wongpakaran, T and Khunachiva, J}, title = {Construct validity, test-retest reliability and internal consistency of the Thai version of the disabilities of the arm, shoulder and hand questionnaire (DASH-TH) in patients with carpal tunnel syndrome.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {208}, pmid = {29587843}, issn = {1756-0500}, mesh = {Adult ; Aged ; Arm/*physiopathology ; Carpal Tunnel Syndrome/diagnosis/*physiopathology ; Disability Evaluation ; Female ; Hand/*physiopathology ; Humans ; Male ; Middle Aged ; Psychometrics ; Reproducibility of Results ; Shoulder/*physiopathology ; Surveys and Questionnaires/*standards ; Thailand ; }, abstract = {OBJECTIVE: This study evaluated additional psychometric properties of the Thai version of the disabilities of the arm, shoulder and hand questionnaire (DASH-TH) which included, test-retest reliability, construct validity, internal consistency of in patients with carpal tunnel syndrome. As for determining construct validity, the Thai EuroQOL questionnaire (EQ-5D-5L) was also administered in order to examine convergent and divergent validity.

RESULTS: Fifty patients completed both questionnaires. The DASH-TH showed excellent test-retest reliability (intraclass correlation coefficient = 0.811) and internal consistency (Cronbach's alpha = 0.911). The exploratory factor analysis yielded a six-factor solution while the confirmatory factor analysis denoted that the hypothesized model adequately fit the data with a comparative fit index of 0.967 and a Tucker-Lewis index of 0.964. The related subscales between the DASH-TH and the Thai EQ-5D-5L were significantly correlated, indicating the DASH-TH's convergent and discriminant validity. The DASH-TH demonstrated good reliability, internal consistency construct validity, and multidimensionality, in assessing the upper extremity function in carpal tunnel syndrome patients.}, } @article {pmid29587833, year = {2018}, author = {Mataki, Y and Kamada, H and Mutsuzaki, H and Shimizu, Y and Takeuchi, R and Mizukami, M and Yoshikawa, K and Takahashi, K and Matsuda, M and Iwasaki, N and Kawamoto, H and Wadano, Y and Sankai, Y and Yamazaki, M}, title = {Use of Hybrid Assistive Limb (HAL®) for a postoperative patient with cerebral palsy: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {201}, pmid = {29587833}, issn = {1756-0500}, support = {14060101-01//Industrial Disease Clinical Research Grants of the Ministry of Health Labour and Welfare, Japan./ ; }, mesh = {Adolescent ; Biomechanical Phenomena ; Cerebral Palsy/physiopathology/*rehabilitation/*surgery ; *Exoskeleton Device ; Humans ; Knee/physiopathology ; Male ; Motion Therapy, Continuous Passive/instrumentation/*methods ; Muscle, Skeletal/physiopathology ; Postoperative Care/methods ; Walking/physiology ; }, abstract = {BACKGROUND: The Hybrid Assistive Limb (HAL®) is an exoskeleton wearable robot suit that assists in voluntary control of knee and hip joint motion. There have been several studies on HAL intervention effects in stroke, spinal cord injury, and cerebral palsy. However, no study has investigated HAL intervention for patients with cerebral palsy after surgery.

CASE PRESENTATION: We report a case of using HAL in a postoperative patient with cerebral palsy. A 15-year-old boy was diagnosed with spastic diplegia cerebral palsy Gross Motor Function Classification System level IV, with knee flection contracture, equinus foot, and paralysis of the right upper extremity with adduction contracture. He underwent tendon lengthening of the bilateral hamstrings and Achilles tendons. Although the flexion contractures of the bilateral knees and equinus foot improved, muscle strength decreased after the soft tissue surgery. HAL intervention was performed twice during postoperative months 10 and 11. Walking speed, stride, and cadence were increased after HAL intervention. Post HAL intervention, extension angles of the knee in stance phase and hip in the pre-swing phase were improved. In the gait cycle, the proportion of terminal stance in the stance and swing phase was increased.

CONCLUSIONS: Hybrid Assistive Limb intervention for postoperative patients with cerebral palsy whose muscle strength decreases can enhance improvement in walking ability. Further studies are needed to examine the safety and potential application of HAL in this setting.}, } @article {pmid29587830, year = {2018}, author = {Gobet, A and Mest, L and Perennou, M and Dittami, SM and Caralp, C and Coulombet, C and Huchette, S and Roussel, S and Michel, G and Leblanc, C}, title = {Seasonal and algal diet-driven patterns of the digestive microbiota of the European abalone Haliotis tuberculata, a generalist marine herbivore.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {60}, pmid = {29587830}, issn = {2049-2618}, support = {ANR-10-BTBR-02-04-11//Agence Nationale de la Recherche/International ; }, mesh = {Animal Feed ; Animals ; Bacteria/classification/genetics ; *Gastrointestinal Microbiome ; Gastropoda/*microbiology ; *Herbivory ; Polysaccharides ; *Seasons ; }, abstract = {BACKGROUND: Holobionts have a digestive microbiota with catabolic abilities allowing the degradation of complex dietary compounds for the host. In terrestrial herbivores, the digestive microbiota is known to degrade complex polysaccharides from land plants while in marine herbivores, the digestive microbiota is poorly characterized. Most of the latter are generalists and consume red, green, and brown macroalgae, three distinct lineages characterized by a specific composition in complex polysaccharides, which represent half of their biomass. Subsequently, each macroalga features a specific epiphytic microbiota, and the digestive microbiota of marine herbivores is expected to vary with a monospecific algal diet. We investigated the effect of four monospecific diets (Palmaria palmata, Ulva lactuca, Saccharina latissima, Laminaria digitata) on the composition and specificity of the digestive microbiota of a generalist marine herbivore, the abalone, farmed in a temperate coastal area over a year. The microbiota from the abalone digestive gland was sampled every 2 months and explored using metabarcoding.

RESULTS: Diversity and multivariate analyses showed that patterns of the microbiota were significantly linked to seasonal variations of contextual parameters but not directly to a specific algal diet. Three core genera: Psychrilyobacter, Mycoplasma, and Vibrio constantly dominated the microbiota in the abalone digestive gland. Additionally, a less abundant and diet-specific core microbiota featured genera representing aerobic primary degraders of algal polysaccharides.

CONCLUSIONS: This study highlights the establishment of a persistent core microbiota in the digestive gland of the abalone since its juvenile state and the presence of a less abundant and diet-specific core community. While composed of different microbial taxa compared to terrestrial herbivores, the digestive gland constitutes a particular niche in the abalone holobiont, where bacteria (i) may cooperate to degrade algal polysaccharides to products assimilable by the host or (ii) may have acquired these functions through gene transfer from the aerobic algal microbiota.}, } @article {pmid29587822, year = {2018}, author = {Ratnayake, D and Newman, M and Lardelli, M}, title = {Degenerate codon mixing for PCR-based manipulation of highly repetitive sequences.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {202}, pmid = {29587822}, issn = {1756-0500}, support = {GNT1061006//National Health and Medical Research Council/ ; }, mesh = {Animals ; Base Sequence ; Codon/*genetics ; Embryo, Nonmammalian/metabolism ; Peptides/*genetics ; Polymerase Chain Reaction/*methods ; Repetitive Sequences, Nucleic Acid/*genetics ; Reproducibility of Results ; Trinucleotide Repeat Expansion/genetics ; Zebrafish/embryology/genetics ; }, abstract = {OBJECTIVE: Repeat expansion of polyglutamine tracks leads to a group of inherited human neurodegenerative disorders. Studying such repetitive sequences is required to gain insight into the pathophysiology of these diseases. PCR-based manipulation of repetitive sequences, however, is challenging due to the absence of unique primer binding sites or the generation of non-specific products.

RESULTS: We have utilised the degeneracy of the genetic code to generate a polyglutamine sequence with low repeat similarity. This strategy allowed us to use conventional PCR to generate multiple constructs with approximately defined numbers of glutamine repeats. We then used these constructs to measure the in vivo variation in autophagic degradation activity related to the different numbers of glutamine repeats, providing an example of their applicability to study repeat expansion diseases. Our simple and easily generalised method of generating low repetition DNA sequences coding for uniform stretches of amino acid residues provides a strategy for generating particular lengths of polyglutamine tracts using standard PCR and cloning protocols.}, } @article {pmid29587750, year = {2018}, author = {Haridas, P and Browning, AP and McGovern, JA and Sean McElwain, DL and Simpson, MJ}, title = {Three-dimensional experiments and individual based simulations show that cell proliferation drives melanoma nest formation in human skin tissue.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {34}, pmid = {29587750}, issn = {1752-0509}, support = {DP170100474//Australian Research Council/ ; }, abstract = {BACKGROUND: Melanoma can be diagnosed by identifying nests of cells on the skin surface. Understanding the processes that drive nest formation is important as these processes could be potential targets for new cancer drugs. Cell proliferation and cell migration are two potential mechanisms that could conceivably drive melanoma nest formation. However, it is unclear which one of these two putative mechanisms plays a dominant role in driving nest formation.

RESULTS: We use a suite of three-dimensional (3D) experiments in human skin tissue and a parallel series of 3D individual-based simulations to explore whether cell migration or cell proliferation plays a dominant role in nest formation. In the experiments we measure nest formation in populations of irradiated (non-proliferative) and non-irradiated (proliferative) melanoma cells, cultured together with primary keratinocyte and fibroblast cells on a 3D experimental human skin model. Results show that nest size depends on initial cell number and is driven primarily by cell proliferation rather than cell migration.

CONCLUSIONS: Nest size depends on cell number, and is driven primarily by cell proliferation rather than cell migration. All experimental results are consistent with simulation data from a 3D individual based model (IBM) of cell migration and cell proliferation.}, } @article {pmid29587653, year = {2018}, author = {Edet, OU and Kim, JS and Okamoto, M and Hanada, K and Takeda, T and Kishii, M and Gorafi, YSA and Tsujimoto, H}, title = {Efficient anchoring of alien chromosome segments introgressed into bread wheat by new Leymus racemosus genome-based markers.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {18}, pmid = {29587653}, issn = {1471-2156}, support = {27307C2007/ES/NIEHS NIH HHS/United States ; KAKENHI 25292039//Japan Society for the Promotion of Science/ ; }, abstract = {BACKGROUND: The tertiary gene pool of bread wheat, to which Leymus racemosus belongs, has remained underutilized due to the current limited genomic resources of the species that constitute it. Continuous enrichment of public databases with useful information regarding these species is, therefore, needed to provide insights on their genome structures and aid successful utilization of their genes to develop improved wheat cultivars for effective management of environmental stresses.

RESULTS: We generated de novo DNA and mRNA sequence information of L. racemosus and developed 110 polymorphic PCR-based markers from the data, and to complement the PCR markers, DArT-seq genotyping was applied to develop additional 9990 SNP markers. Approximately 52% of all the markers enabled us to clearly genotype 22 wheat-L. racemosus chromosome introgression lines, and L. racemosus chromosome-specific markers were highly efficient in detailed characterization of the translocation and recombination lines analyzed. A further analysis revealed remarkable transferability of the PCR markers to three other important Triticeae perennial species: L. mollis, Psathyrostachys huashanica and Elymus ciliaris, indicating their suitability for characterizing wheat-alien chromosome introgressions carrying chromosomes of these genomes.

CONCLUSION: The efficiency of the markers in characterizing wheat-L. racemosus chromosome introgression lines proves their reliability, and their high transferability further broadens their scope of application. This is the first report on sequencing and development of markers from L. racemosus genome and the application of DArT-seq to develop markers from a perennial wild relative of wheat, marking a paradigm shift from the seeming concentration of the technology on cultivated species. Integration of these markers with appropriate cytogenetic methods would accelerate development and characterization of wheat-alien chromosome introgression lines.}, } @article {pmid29587652, year = {2018}, author = {Chang, YK and Zuo, Z and Stormo, GD}, title = {Quantitative profiling of BATF family proteins/JUNB/IRF hetero-trimers using Spec-seq.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {5}, pmid = {29587652}, issn = {1471-2199}, support = {HG000249/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Basic-Leucine Zipper Transcription Factors/chemistry/genetics/*metabolism ; Binding Sites ; Humans ; Interferon Regulatory Factors/chemistry/*genetics/metabolism ; Mice ; Protein Multimerization ; Repressor Proteins/chemistry/genetics/metabolism ; Sequence Analysis, DNA/*methods ; Transcription Factors/chemistry/*genetics/metabolism ; Tumor Suppressor Proteins/chemistry/genetics/metabolism ; }, abstract = {BACKGROUND: BATF family transcription factors (BATF, BATF2 and BATF3) form hetero-trimers with JUNB and either IRF4 or IRF8 to regulate cell fate in T cells and dendritic cells in vivo. While each combination of the hetero-trimer has a distinct role, some degree of cross-compensation was observed. The basis for the differential actions of IRF4 and IRF8 with BATF factors and JUNB is still unknown. We propose that the differences in function between these hetero-trimers may be caused by differences in their DNA binding preferences. While all three BATF family transcription factors have similar binding preferences when binding as a hetero-dimer with JUNB, the cooperative binding of IRF4 or IRF8 to the hetero-dimer/DNA complex could change the preferences. We used Spec-seq, which allows for the efficient and accurate determination of relative affinity to a large collection of sequences in parallel, to find differences between cooperative DNA binding of IRF4, IRF8 and BATF family members.

RESULTS: We found that without IRF binding, all three hetero-dimer pairs exhibit nearly the same binding preferences to both expected wildtype binding sites TRE (TGA(C/G)TCA) and CRE (TGACGTCA). IRF4 and IRF8 show the very similar DNA binding preferences when binding with any of the three hetero-dimers. No major change of binding preferences was found in the half-sites between different hetero-trimers. IRF proteins bind with substantially lower affinity with either a single nucleotide spacer between IRF and BATF binding site or with an alternative mode of binding in the opposite orientation. In addition, the preference to CRE binding site was reduced with either IRF binding in all BATF-JUNB combinations.

CONCLUSIONS: The specificities of BATF, BATF2 and BATF3 are all very similar as are their interactions with IRF4 and IRF8. IRF proteins binding adjacent to BATF sites increases affinity substantially compared to sequences with spacings between the sites, indicating cooperative binding through protein-protein interactions. The preference for the type of BATF binding site, TRE or CRE, is also altered when IRF proteins bind. These in vitro preferences aid in the understanding of in vivo binding activities.}, } @article {pmid29587648, year = {2018}, author = {Zeng, X and Xu, Y and Jiang, J and Zhang, F and Ma, L and Wu, D and Wang, Y and Sun, W}, title = {Identification of cold stress responsive microRNAs in two winter turnip rape (Brassica rapa L.) by high throughput sequencing.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {52}, pmid = {29587648}, issn = {1471-2229}, support = {31560397//National Natural Science Foundation of China/ ; 31460356//National Natural Science Foundation of China/ ; 31660401//National Natural Science Foundation of China/ ; 2015CB150201//National Key Basic Research Program of China/ ; 1506RJZG051, 145RJZG050//the Natural Science Foundation of Gansu Province/ ; }, mesh = {Brassica rapa/*genetics ; Cold Temperature ; Gene Expression Regulation, Plant/genetics ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; RNA, Plant/*genetics ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Low temperature is a major abiotic stress affecting the production of rapeseed in China by impeding plant growth and development. A comprehensive knowledge of small-RNA expression pattern in Brassica rapa under cold stress could improve our knowledge of microRNA-mediated stress responses.

RESULTS: A total of 353 cold-responsive miRNAs, 84 putative novel and 269 conserved miRNAs, were identified from the leaves and roots of two winter turnip rape varieties 'Longyou 7' (cold-tolerant) and 'Tianyou 4' (cold-sensitive), which were stressed under - 4 °C for 8 h. Eight conserved (miR166h-3p-1, miR398b-3p, miR398b-3p-1, miR408d, miR156a-5p, miR396h, miR845a-1, miR166u) and two novel miRNAs (Bra-novel-miR3153-5p and Bra-novel-miR3172-5p) were differentially expressed in leaves of 'Longyou 7' under cold stress. Bra-novel-miR3936-5p was up-regulated in roots of 'Longyou 7' under cold stress. Four and five conserved miRNAs were differentially expressed in leaves and roots of 'Tianyou 4' after cold stress. Besides, we found two conserved miRNAs (miR319e and miR166m-2) were down-regulated in non-stressed roots of 'Longyou 7' compared with 'Tianyou 4'. After cold stress, we found two and eight miRNAs were differentially expressed in leaves and roots of 'Longyou 7' compared with 'Tianyou 4'. The differentially expressed miRNAs between two cultivars under cold stress include novel miRNAs and the members of the miR166 and miR319 families. A total of 211 target genes for 15 known miRNAs and two novel miRNAs were predicted by bioinformatic analysis, mainly involved in metabolic processes and stress responses. Five differentially expressed miRNAs and predicted target genes were confirmed by quantitative reverse transcription PCR, and the expressional changes of target genes were negatively correlated to differentially expressed miRNAs. Our data indicated that some candidate miRNAs (e.g., miR166e, miR319, and Bra-novel-miR3936-5p) may play important roles in plant response to cold stress.

CONCLUSIONS: Our work indicates that miRNA and putative target genes mediated metabolic processes and stress responses are significant to cold tolerance in B. rapa.}, } @article {pmid29587647, year = {2018}, author = {Stange, M and Aguirre-Fernández, G and Salzburger, W and Sánchez-Villagra, MR}, title = {Study of morphological variation of northern Neotropical Ariidae reveals conservatism despite macrohabitat transitions.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {38}, pmid = {29587647}, issn = {1471-2148}, support = {FK-15-092//Forschungskredit from the University of Zurich/International ; CRSII3_136293//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung (CH)/International ; CRSII3_136293//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; CICHLID~X//European Research Council/International ; }, mesh = {Animals ; Catfishes/*anatomy & histology/classification ; *Ecosystem ; Fresh Water ; Geography ; Phylogeny ; Skull/anatomy & histology ; *Tropical Climate ; }, abstract = {BACKGROUND: Morphological convergence triggered by trophic adaptations is a common pattern in adaptive radiations. The study of shape variation in an evolutionary context is usually restricted to well-studied fish models. We take advantage of the recently revised systematics of New World Ariidae and investigate skull shape evolution in six genera of northern Neotropical Ariidae. They constitute a lineage that diversified in the marine habitat but repeatedly adapted to freshwater habitats. 3D geometric morphometrics was applied for the first time in catfish skulls and phylogenetically informed statistical analyses were performed to test for the impact of habitat on skull diversification after habitat transition in this lineage.

RESULTS: We found that skull shape is conserved throughout phylogeny. A morphospace analysis revealed that freshwater and marine species occupy extreme ends of the first principal component axis and that they exhibit similar Procrustes variances. Yet freshwater species occupy the smallest shape space compared to marine and brackish species (based on partial disparity), and marine and freshwater species have the largest Procrustes distance to each other. We observed a single case of shape convergence as derived from 'C-metrics', which cannot be explained by the occupation of the same habitat.

CONCLUSIONS: Although Ariidae occupy such a broad spectrum of different habitats from sea to freshwater, the morphospace analysis and analyses of shape and co-variation with habitat in a phylogenetic context shows that conservatism dominates skull shape evolution among ariid genera.}, } @article {pmid29587646, year = {2018}, author = {Liang, K and Du, C and You, H and Nettleton, D}, title = {A hidden Markov tree model for testing multiple hypotheses corresponding to Gene Ontology gene sets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {107}, pmid = {29587646}, issn = {1471-2105}, support = {R01 GM109458/GM/NIGMS NIH HHS/United States ; 435666-2013//NSERC/International ; DMS1313224//National Science Foundation/International ; R01GM109458/NH/NIH HHS/United States ; }, mesh = {Algorithms ; Bayes Theorem ; Computer Simulation ; *Gene Ontology ; Humans ; *Markov Chains ; *Models, Genetic ; *Models, Theoretical ; Quantitative Trait Loci/genetics ; ROC Curve ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Testing predefined gene categories has become a common practice for scientists analyzing high throughput transcriptome data. A systematic way of testing gene categories leads to testing hundreds of null hypotheses that correspond to nodes in a directed acyclic graph. The relationships among gene categories induce logical restrictions among the corresponding null hypotheses. An existing fully Bayesian method is powerful but computationally demanding.

RESULTS: We develop a computationally efficient method based on a hidden Markov tree model (HMTM). Our method is several orders of magnitude faster than the existing fully Bayesian method. Through simulation and an expression quantitative trait loci study, we show that the HMTM method provides more powerful results than other existing methods that honor the logical restrictions.

CONCLUSIONS: The HMTM method provides an individual estimate of posterior probability of being differentially expressed for each gene set, which can be useful for result interpretation. The R package can be found on https://github.com/k22liang/HMTGO .}, } @article {pmid29587645, year = {2018}, author = {Mojarro, A and Hachey, J and Ruvkun, G and Zuber, MT and Carr, CE}, title = {CarrierSeq: a sequence analysis workflow for low-input nanopore sequencing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {108}, pmid = {29587645}, issn = {1471-2105}, support = {NNX15AF85G/NASA/NASA/United States ; }, mesh = {Bacillus subtilis/genetics ; *Nanopores ; ROC Curve ; Sequence Analysis, DNA/*methods ; *Software ; *Workflow ; }, abstract = {BACKGROUND: Long-read nanopore sequencing technology is of particular significance for taxonomic identification at or below the species level. For many environmental samples, the total extractable DNA is far below the current input requirements of nanopore sequencing, preventing "sample to sequence" metagenomics from low-biomass or recalcitrant samples.

RESULTS: Here we address this problem by employing carrier sequencing, a method to sequence low-input DNA by preparing the target DNA with a genomic carrier to achieve ideal library preparation and sequencing stoichiometry without amplification. We then use CarrierSeq, a sequence analysis workflow to identify the low-input target reads from the genomic carrier. We tested CarrierSeq experimentally by sequencing from a combination of 0.2 ng Bacillus subtilis ATCC 6633 DNA in a background of 1000 ng Enterobacteria phage λ DNA. After filtering of carrier, low quality, and low complexity reads, we detected target reads (B. subtilis), contamination reads, and "high quality noise reads" (HQNRs) not mapping to the carrier, target or known lab contaminants. These reads appear to be artifacts of the nanopore sequencing process as they are associated with specific channels (pores).

CONCLUSION: By treating sequencing as a Poisson arrival process, we implement a statistical test to reject data from channels dominated by HQNRs while retaining low-input target reads.}, } @article {pmid29587643, year = {2018}, author = {Walitang, DI and Kim, CG and Kim, K and Kang, Y and Kim, YK and Sa, T}, title = {The influence of host genotype and salt stress on the seed endophytic community of salt-sensitive and salt-tolerant rice cultivars.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {51}, pmid = {29587643}, issn = {1471-2229}, support = {2015R1A2A1A05001885//National Research Foundation of Korea/ ; }, mesh = {Actinobacteria/genetics/physiology ; Endophytes/classification/genetics/physiology ; Firmicutes/genetics/physiology ; Genotype ; Oryza/*drug effects/genetics/*microbiology ; Phylogeny ; Polymorphism, Restriction Fragment Length/genetics ; Proteobacteria/genetics/physiology ; RNA, Ribosomal, 16S/genetics ; Seeds/*drug effects/genetics/*microbiology ; }, abstract = {BACKGROUND: Inherent characteristics and changes in the physiology of rice as it attains salt tolerance affect the colonizing bacterial endophytic communities of the rice seeds. These transmissible endophytes also serve as a source of the plant's microbial community and concurrently respond to the host and environmental conditions. This study explores the influence of the rice host as well as the impact of soil salinity on the community structure and diversity of seed bacterial endophytes of rice with varying tolerance to salt stress. Endophytic bacterial diversity was studied through culture-dependent technique and Terminal-Restriction Fragment Length Polymorphism (T-RFLP) analysis.

RESULTS: Results revealed considerably diverse communities of bacterial endophytes in the interior of rice seeds. The overall endophytic bacterial communities of the indica rice seeds based on 16S rRNA analysis of clones and isolates are dominated by phylum Proteobacteria followed by Actinobacteria and Firmicutes. Community profiles show common ribotypes found in all cultivars of the indica subspecies representing potential core microbiota belonging to Curtobacterium, Flavobacterium, Enterobacter, Xanthomonas, Herbaspirillum, Microbacterium and Stenotrophomonas. Clustering analysis shows that the host genotype mainly influences the seed endophytic community of the different rice cultivars. Under salt stress conditions, endophytic communities of the salt-sensitive and salt-tolerant rice cultivars shift their dominance to bacterial groups belonging to Flavobacterium, Pantoea, Enterobacter, Microbacterium, Kosakonia and Curtobacterium.

CONCLUSION: The endophytic communities of rice indica seeds are shaped by the hosts' genotype, their physiological adaptation to salt stress and phylogenetic relatedness. Under salt stress conditions, a few groups of bacterial communities become prominent causing a shift in bacterial diversity and dominance.}, } @article {pmid29587637, year = {2018}, author = {Zhang, X and Wang, W and Guo, N and Zhang, Y and Bu, Y and Zhao, J and Xing, H}, title = {Combining QTL-seq and linkage mapping to fine map a wild soybean allele characteristic of greater plant height.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {226}, pmid = {29587637}, issn = {1471-2164}, support = {2017YFD0101500//National Key R&D Program of China/International ; 2017YFD0102002//National Key R&D Program of China/International ; Grant No.31301343//National Natural Science Foundation of China/International ; CARS-004-PS10//Modern Agro-industry Technology Research System of China/International ; }, mesh = {Alleles ; Amino Acid Sequence ; Chromosome Mapping/*methods ; *Chromosomes, Plant ; *Genetic Linkage ; Genotype ; Phenotype ; Plant Proteins/genetics ; *Quantitative Trait Loci ; Seeds/genetics/growth & development ; Sequence Homology ; Soybeans/*genetics/*growth & development ; }, abstract = {BACKGROUND: Plant height (PH) is an important agronomic trait and is closely related to yield in soybean [Glycine max (L.) Merr.]. Previous studies have identified many QTLs for PH. Due to the complex genetic background of PH in soybean, there are few reports on its fine mapping.

RESULTS: In this study, we used a mapping population derived from a cross between a chromosome segment substitution line CSSL3228 (donor N24852 (G. Soja), a receptor NN1138-2 (G. max)) and NN1138-2 to fine map a wild soybean allele of greater PH by QTL-seq and linkage mapping. We identified a QTL for PH in a 1.73 Mb region on soybean chromosome 13 through QTL-seq, which was confirmed by SSR marker-based classical QTL mapping in the mapping population. The linkage analysis showed that the QTLs of PH were located between the SSR markers BARCSOYSSR_13_1417 and BARCSOYSSR_13_1421 on chromosome 13, and the physical distance was 69.3 kb. RT-PCR and sequence analysis of possible candidate genes showed that Glyma.13 g249400 revealed significantly higher expression in higher PH genotypes, and the gene existed 6 differences in the amino acids encoding between the two parents.

CONCLUSIONS: Data presented here provide support for Glyma.13 g249400 as a possible candidate genes for higher PH in wild soybean line N24852.}, } @article {pmid29587635, year = {2018}, author = {Isaacs, AT and Mawejje, HD and Tomlinson, S and Rigden, DJ and Donnelly, MJ}, title = {Genome-wide transcriptional analyses in Anopheles mosquitoes reveal an unexpected association between salivary gland gene expression and insecticide resistance.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {225}, pmid = {29587635}, issn = {1471-2164}, support = {U19 AI089674/AI/NIAID NIH HHS/United States ; U19AI089674//National Institute of Allergy and Infectious Diseases/International ; }, mesh = {Animals ; Anopheles/classification/drug effects/*genetics ; Genome, Insect ; Insect Proteins/*genetics ; *Insecticide Resistance ; Insecticides/*pharmacology ; *Polymorphism, Single Nucleotide ; Salivary Glands/drug effects/*metabolism/parasitology ; }, abstract = {BACKGROUND: To combat malaria transmission, the Ugandan government has embarked upon an ambitious programme of indoor residual spraying (IRS) with a carbamate class insecticide, bendiocarb. In preparation for this campaign, we characterized bendiocarb resistance and associated transcriptional variation among Anopheles gambiae s.s. mosquitoes from two sites in Uganda.

RESULTS: Gene expression in two mosquito populations displaying some resistance to bendiocarb (95% and 79% An. gambiae s.l. WHO tube bioassay mortality in Nagongera and Kihihi, respectively) was investigated using whole-genome microarrays. Significant overexpression of several genes encoding salivary gland proteins, including D7r2 and D7r4, was detected in mosquitoes from Nagongera. In Kihihi, D7r4, two detoxification-associated genes (Cyp6m2 and Gstd3) and an epithelial serine protease were among the genes most highly overexpressed in resistant mosquitoes. Following the first round of IRS in Nagongera, bendiocarb-resistant mosquitoes were collected, and real-time quantitative PCR analyses detected significant overexpression of D7r2 and D7r4 in resistant mosquitoes. A single nucleotide polymorphism located in a non-coding transcript downstream of the D7 genes was found at a significantly higher frequency in resistant individuals. In silico modelling of the interaction between D7r4 and bendiocarb demonstrated similarity between the insecticide and serotonin, a known ligand of D7 proteins. A meta-analysis of published microarray studies revealed a recurring association between D7 expression and insecticide resistance across Anopheles species and locations.

CONCLUSIONS: A whole-genome microarray approach identified an association between novel insecticide resistance candidates and bendiocarb resistance in Uganda. In addition, a single nucleotide polymorphism associated with this resistance mechanism was discovered. The use of such impartial screening methods allows for discovery of resistance candidates that have no previously-ascribed function in insecticide binding or detoxification. Characterizing these novel candidates will broaden our understanding of resistance mechanisms and yield new strategies for combatting widespread insecticide resistance among malaria vectors.}, } @article {pmid29587634, year = {2018}, author = {Gill, EE and Chan, LS and Winsor, GL and Dobson, N and Lo, R and Ho Sui, SJ and Dhillon, BK and Taylor, PK and Shrestha, R and Spencer, C and Hancock, REW and Unrau, PJ and Brinkman, FSL}, title = {High-throughput detection of RNA processing in bacteria.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {223}, pmid = {29587634}, issn = {1471-2164}, support = {//CIHR/Canada ; }, mesh = {Chromosome Mapping ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Promoter Regions, Genetic ; Pseudomonas aeruginosa/*genetics/growth & development ; *RNA Processing, Post-Transcriptional ; RNA, Bacterial/*genetics ; Sequence Analysis, RNA ; *Transcription Initiation Site ; }, abstract = {BACKGROUND: Understanding the RNA processing of an organism's transcriptome is an essential but challenging step in understanding its biology. Here we investigate with unprecedented detail the transcriptome of Pseudomonas aeruginosa PAO1, a medically important and innately multi-drug resistant bacterium. We systematically mapped RNA cleavage and dephosphorylation sites that result in 5'-monophosphate terminated RNA (pRNA) using monophosphate RNA-Seq (pRNA-Seq). Transcriptional start sites (TSS) were also mapped using differential RNA-Seq (dRNA-Seq) and both datasets were compared to conventional RNA-Seq performed in a variety of growth conditions.

RESULTS: The pRNA-Seq library revealed known tRNA, rRNA and transfer-messenger RNA (tmRNA) processing sites, together with previously uncharacterized RNA cleavage events that were found disproportionately near the 5' ends of transcripts associated with basic bacterial functions such as oxidative phosphorylation and purine metabolism. The majority (97%) of the processed mRNAs were cleaved at precise codon positions within defined sequence motifs indicative of distinct endonucleolytic activities. The most abundant of these motifs corresponded closely to an E. coli RNase E site previously established in vitro. Using the dRNA-Seq library, we performed an operon analysis and predicted 3159 potential TSS. A correlation analysis uncovered 105 antiparallel pairs of TSS that were separated by 18 bp from each other and were centered on single palindromic TAT(A/T)ATA motifs (likely - 10 promoter elements), suggesting that, consistent with previous in vitro experimentation, these sites can initiate transcription bi-directionally and may thus provide a novel form of transcriptional regulation. TSS and RNA-Seq analysis allowed us to confirm expression of small non-coding RNAs (ncRNAs), many of which are differentially expressed in swarming and biofilm formation conditions.

CONCLUSIONS: This study uses pRNA-Seq, a method that provides a genome-wide survey of RNA processing, to study the bacterium Pseudomonas aeruginosa and discover extensive transcript processing not previously appreciated. We have also gained novel insight into RNA maturation and turnover as well as a potential novel form of transcription regulation. NOTE: All sequence data has been submitted to the NCBI sequence read archive. Accession numbers are as follows: [NCBI sequence read archive: SRX156386, SRX157659, SRX157660, SRX157661, SRX157683 and SRX158075]. The sequence data is viewable using Jbrowse on www.pseudomonas.com .}, } @article {pmid29587633, year = {2018}, author = {Chase, EE and Robicheau, BM and Veinot, S and Breton, S and Stewart, DT}, title = {The complete mitochondrial genome of the hermaphroditic freshwater mussel Anodonta cygnea (Bivalvia: Unionidae): in silico analyses of sex-specific ORFs across order Unionoida.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {221}, pmid = {29587633}, issn = {1471-2164}, support = {217175//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {Animals ; Computer Simulation ; DNA, Mitochondrial/genetics ; Disorders of Sex Development/*genetics ; Female ; Fresh Water ; *Genome, Mitochondrial ; Male ; Mitochondrial Proteins/genetics ; *Open Reading Frames ; Phylogeny ; Sex Factors ; Unionidae/classification/*genetics ; }, abstract = {BACKGROUND: Doubly uniparental inheritance (DUI) of mitochondrial DNA in bivalves is a fascinating exception to strictly maternal inheritance as practiced by all other animals. Recent work on DUI suggests that there may be unique regions of the mitochondrial genomes that play a role in sex determination and/or sexual development in freshwater mussels (order Unionoida). In this study, one complete mitochondrial genome of the hermaphroditic swan mussel, Anodonta cygnea, is sequenced and compared to the complete mitochondrial genome of the gonochoric duck mussel, Anodonta anatina. An in silico assessment of novel proteins found within freshwater bivalve species (known as F-, H-, and M-open reading frames or ORFs) is conducted, with special attention to putative transmembrane domains (TMs), signal peptides (SPs), signal cleavage sites (SCS), subcellular localization, and potential control regions. Characteristics of TMs are also examined across freshwater mussel lineages.

RESULTS: In silico analyses suggests the presence of SPs and SCSs and provides some insight into possible function(s) of these novel ORFs. The assessed confidence in these structures and functions was highly variable, possibly due to the novelty of these proteins. The number and topology of putative TMs appear to be maintained among both F- and H-ORFs, however, this is not the case for M-ORFs. There does not appear to be a typical control region in H-type mitochondrial DNA, especially given the loss of tandem repeats in unassigned regions when compared to F-type mtDNA.

CONCLUSION: In silico analyses provides a useful tool to discover patterns in DUI and to navigate further in situ analyses related to DUI in freshwater mussels. In situ analysis will be necessary to further explore the intracellular localizations and possible role of these open reading frames in the process of sex determination in freshwater mussel.}, } @article {pmid29587632, year = {2018}, author = {Alam, MN and Zhang, L and Yang, L and Islam, MR and Liu, Y and Luo, H and Yang, P and Wang, Q and Chan, Z}, title = {Transcriptomic profiling of tall fescue in response to heat stress and improved thermotolerance by melatonin and 24-epibrassinolide.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {224}, pmid = {29587632}, issn = {1471-2164}, support = {2017YFD0201305//National Key Research and Development Program/International ; 2016RC010//Huazhong Agricultural University Scientific & Technological Self-Innovation Foundation/International ; }, mesh = {Antioxidants/pharmacology ; Brassinosteroids/*pharmacology ; Chlorophyll/metabolism ; Energy Metabolism ; Festuca/drug effects/*genetics/growth & development ; Gene Expression Regulation, Plant/*drug effects ; Heat-Shock Response/drug effects/genetics ; Hot Temperature/*adverse effects ; Melatonin/*pharmacology ; Plant Growth Regulators/pharmacology ; Plant Proteins/*genetics ; Seedlings/drug effects/genetics/growth & development ; Steroids, Heterocyclic/*pharmacology ; Stress, Physiological ; Thermotolerance/*genetics ; }, abstract = {BACKGROUND: Tall fescue is a widely used cool season turfgrass and relatively sensitive to high temperature. Chemical compounds like melatonin (MT) and 24-epibrassinolide (EBL) have been reported to improve plant heat stress tolerance effectively.

RESULTS: In this study, we reported that MT and EBL pretreated tall fescue seedlings showed decreased reactive oxygen species (ROS), electrolyte leakage (EL) and malondialdehide (MDA), but increased chlorophyll (Chl), total protein and antioxidant enzyme activities under heat stress condition, resulting in improved plant growth. Transcriptomic profiling analysis showed that 4311 and 8395 unigenes were significantly changed after 2 h and 12 h of heat treatments, respectively. Among them, genes involved in heat stress responses, DNA, RNA and protein degradation, redox, energy metabolisms, and hormone metabolism pathways were highly induced after heat stress. Genes including FaHSFA3, FaAWPM and FaCYTC2 were significantly upregulated by both MT and EBL treatments, indicating that these genes might function as the putative target genes of MT and EBL.

CONCLUSIONS: These findings indicated that heat stress caused extensively transcriptomic reprogramming of tall fescue and exogenous application of MT and EBL effectively improved thermotolerance in tall fescue.}, } @article {pmid29587631, year = {2018}, author = {Zhou, G and Kang, D and Ma, S and Wang, X and Gao, Y and Yang, Y and Wang, X and Chen, Y}, title = {Integrative analysis reveals ncRNA-mediated molecular regulatory network driving secondary hair follicle regression in cashmere goats.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {222}, pmid = {29587631}, issn = {1471-2164}, support = {31372279//National Natural Science Foundation of China (CN)/International ; 31572369//National Natural Science Foundation of China/International ; 31772571//National Natural Science Foundation of China/International ; 31402038//National Natural Science Foundation of China/International ; CARS-39//China Agriculture Research System/International ; 2017NY-072//Key Research Program of Shaanxi Province/International ; }, mesh = {Animals ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; *Gene Regulatory Networks ; Genomics ; Goats/*genetics/*growth & development ; Hair Follicle/*growth & development ; MicroRNAs/genetics ; Molecular Sequence Annotation ; RNA, Messenger/genetics ; RNA, Untranslated/*genetics ; Skin/growth & development/metabolism ; }, abstract = {BACKGROUND: Cashmere is a keratinized product derived from the secondary hair follicles (SHFs) of cashmere goat skins. The cashmere fiber stops growing following the transition from the actively proliferating anagen stage to the apoptosis-driven catagen stage. However, little is known regarding the molecular mechanisms responsible for the occurrence of apoptosis in SHFs, especially as pertains to the role of non-coding RNAs (ncRNAs) and their interactions with other molecules. Hair follicle (HF) degeneration is caused by localized apoptosis in the skin, while anti-apoptosis pathways may coexist in adjacent HFs. Thus, elucidating the molecular interactions responsible for apoptosis and anti-apoptosis in the skin will provide insights into HF regression.

RESULTS: We used multiple-omics approaches to systematically identify long non-coding RNAs (lncRNAs), microRNAs (miRNAs) and mRNAs expressed in cashmere goat skins in two crucial phases (catagen vs. anagen) of HF growth. Skin samples were collected from three cashmere goats at the anagen (September) and catagen (February) stages, and six lncRNA libraries and six miRNA libraries were constructed for further analysis. We identified 1122 known and 403 novel lncRNAs in the goat skins, 173 of which were differentially expressed between the anagen and catagen stages. We further identified 3500 gene-encoding transcripts that were differentially expressed between these two phases. We also identified 411 known miRNAs and 307 novel miRNAs, including 72 differentially expressed miRNAs. We further investigated the target genes of lncRNAs via both cis- and trans-regulation during HF growth. Our data suggest that lncRNAs and miRNAs act synergistically in the HF growth transition, and the catagen inducer factors (TGFβ1 and BDNF) were regulated by miR-873 and lnc108635596 in the lncRNA-miRNA-mRNA networks.

CONCLUSION: This study enriches the repertoire of ncRNAs in goats and other mammals, and contributes to a better understanding of the molecular mechanisms of ncRNAs involved in the regulation of HF growth and regression in goats and other hair-producing species.}, } @article {pmid29587630, year = {2018}, author = {Bulla, I and Aliaga, B and Lacal, V and Bulla, J and Grunau, C and Chaparro, C}, title = {Notos - a galaxy tool to analyze CpN observed expected ratios for inferring DNA methylation types.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {105}, pmid = {29587630}, issn = {1471-2105}, support = {34040YK//Campus France/International ; 34040YK//Norges Forskningsråd/International ; BU 26854-1//Deutsche Forschungsgemeinschaft/International ; ANR-10-BLAN-1720//Agence Nationale pour la Recherche (FR)/International ; }, mesh = {Alligators and Crocodiles/genetics ; Animals ; Citrus/genetics ; Cluster Analysis ; *CpG Islands ; DNA Methylation/*genetics ; Grasshoppers/genetics ; Humans ; Moths/genetics ; Neurospora crassa/genetics ; *Software ; }, abstract = {BACKGROUND: DNA methylation patterns store epigenetic information in the vast majority of eukaryotic species. The relatively high costs and technical challenges associated with the detection of DNA methylation however have created a bias in the number of methylation studies towards model organisms. Consequently, it remains challenging to infer kingdom-wide general rules about the functions and evolutionary conservation of DNA methylation. Methylated cytosine is often found in specific CpN dinucleotides, and the frequency distributions of, for instance, CpG observed/expected (CpG o/e) ratios have been used to infer DNA methylation types based on higher mutability of methylated CpG.

RESULTS: Predominantly model-based approaches essentially founded on mixtures of Gaussian distributions are currently used to investigate questions related to the number and position of modes of CpG o/e ratios. These approaches require the selection of an appropriate criterion for determining the best model and will fail if empirical distributions are complex or even merely moderately skewed. We use a kernel density estimation (KDE) based technique for robust and precise characterization of complex CpN o/e distributions without a priori assumptions about the underlying distributions.

CONCLUSIONS: We show that KDE delivers robust descriptions of CpN o/e distributions. For straightforward processing, we have developed a Galaxy tool, called Notos and available at the ToolShed, that calculates these ratios of input FASTA files and fits a density to their empirical distribution. Based on the estimated density the number and shape of modes of the distribution is determined, providing a rational for the prediction of the number and the types of different methylation classes. Notos is written in R and Perl.}, } @article {pmid29587629, year = {2018}, author = {Ghartey-Kwansah, G and Li, Z and Feng, R and Wang, L and Zhou, X and Chen, FZ and Xu, MM and Jones, O and Mu, Y and Chen, S and Bryant, J and Isaacs, WB and Ma, J and Xu, X}, title = {Comparative analysis of FKBP family protein: evaluation, structure, and function in mammals and Drosophila melanogaster.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {7}, pmid = {29587629}, issn = {1471-213X}, support = {31371256/31571273/31771277//by the National Natural Science Foundation of China/International ; MS2014SXSF038//the Foreign Distinguished Scientist Program from the National Department of Education/International ; GK20130100/201701005/GERP-17-45//the National Department of Education Central Universities Research Fund/International ; 2015CB943100//Ministry of Science and Technology of the People's Republic of China/International ; 2009MSCRFE008300//US Maryland Stem Cell Research Fund/International ; X2014YB02/X2015YB05//the Outstanding Doctoral Thesis fund/International ; }, abstract = {BACKGROUND: FK506-binding proteins (FKBPs) have become the subject of considerable interest in several fields, leading to the identification of several cellular and molecular pathways in which FKBPs impact prenatal development and pathogenesis of many human diseases.

MAIN BODY: This analysis revealed differences between how mammalian and Drosophila FKBPs mechanisms function in relation to the immunosuppressant drugs, FK506 and rapamycin. Differences that could be used to design insect-specific pesticides. (1) Molecular phylogenetic analysis of FKBP family proteins revealed that the eight known Drosophila FKBPs share homology with the human FKBP12. This indicates a close evolutionary relationship, and possible origination from a common ancestor. (2) The known FKBPs contain FK domains, that is, a prolyl cis/trans isomerase (PPIase) domain that mediates immune suppression through inhibition of calcineurin. The dFKBP59, CG4735/Shutdown, CG1847, and CG5482 have a Tetratricopeptide receptor domain at the C-terminus, which regulates transcription and protein transportation. (3) FKBP51 and FKBP52 (dFKBP59), along with Cyclophilin 40 and protein phosphatase 5, function as Hsp90 immunophilin co-chaperones within steroid receptor-Hsp90 heterocomplexes. These immunophilins are potential drug targets in pathways associated with normal physiology and may be used to treat a variety of steroid-based diseases by targeting exocytic/endocytic cycling and vesicular trafficking. (4) By associating with presinilin, a critical component of the Notch signaling pathway, FKBP14 is a downstream effector of Notch activation at the membrane. Meanwhile, Shutdown associates with transposons in the PIWI-interacting RNA pathway, playing a crucial role in both germ cells and ovarian somas. Mutations in or silencing of dFKBPs lead to early embryonic lethality in Drosophila. Therefore, further understanding the mechanisms of FK506 and rapamycin binding to immunophilin FKBPs in endocrine, cardiovascular, and neurological function in both mammals and Drosophila would provide prospects in generating unique, insect specific therapeutics targeting the above cellular signaling pathways.

CONCLUSION: This review will evaluate the functional roles of FKBP family proteins, and systematically summarize the similarities and differences between FKBP proteins in Drosophila and Mammals. Specific therapeutics targeting cellular signaling pathways will also be discussed.}, } @article {pmid29587628, year = {2018}, author = {Sinoquet, C}, title = {A method combining a random forest-based technique with the modeling of linkage disequilibrium through latent variables, to run multilocus genome-wide association studies.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {106}, pmid = {29587628}, issn = {1471-2105}, mesh = {*Algorithms ; Bayes Theorem ; Chromosomes, Human, Pair 22/genetics ; Computer Simulation ; Databases, Genetic ; *Genetic Loci ; *Genome-Wide Association Study ; Humans ; Linkage Disequilibrium/*genetics ; *Models, Genetic ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; }, abstract = {BACKGROUND: Genome-wide association studies (GWASs) have been widely used to discover the genetic basis of complex phenotypes. However, standard single-SNP GWASs suffer from lack of power. In particular, they do not directly account for linkage disequilibrium, that is the dependences between SNPs (Single Nucleotide Polymorphisms).

RESULTS: We present the comparative study of two multilocus GWAS strategies, in the random forest-based framework. The first method, T-Trees, was designed by Botta and collaborators (Botta et al., PLoS ONE 9(4):e93379, 2014). We designed the other method, which is an innovative hybrid method combining T-Trees with the modeling of linkage disequilibrium. Linkage disequilibrium is modeled through a collection of tree-shaped Bayesian networks with latent variables, following our former works (Mourad et al., BMC Bioinformatics 12(1):16, 2011). We compared the two methods, both on simulated and real data. For dominant and additive genetic models, in either of the conditions simulated, the hybrid approach always slightly performs better than T-Trees. We assessed predictive powers through the standard ROC technique on 14 real datasets. For 10 of the 14 datasets analyzed, the already high predicted power observed for T-Trees (0.910-0.946) can still be increased by up to 0.030. We also assessed whether the distributions of SNPs' scores obtained from T-Trees and the hybrid approach differed. Finally, we thoroughly analyzed the intersections of top 100 SNPs output by any two or the three methods amongst T-Trees, the hybrid approach, and the single-SNP method.

CONCLUSIONS: The sophistication of T-Trees through finer linkage disequilibrium modeling is shown beneficial. The distributions of SNPs' scores generated by T-Trees and the hybrid approach are shown statistically different, which suggests complementary of the methods. In particular, for 12 of the 14 real datasets, the distribution tail of highest SNPs' scores shows larger values for the hybrid approach. Thus are pinpointed more interesting SNPs than by T-Trees, to be provided as a short list of prioritized SNPs, for a further analysis by biologists. Finally, among the 211 top 100 SNPs jointly detected by the single-SNP method, T-Trees and the hybrid approach over the 14 datasets, we identified 72 and 38 SNPs respectively present in the top25s and top10s for each method.}, } @article {pmid29587627, year = {2018}, author = {Van Deun, K and Crompvoets, EAV and Ceulemans, E}, title = {Obtaining insights from high-dimensional data: sparse principal covariates regression.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {104}, pmid = {29587627}, issn = {1471-2105}, support = {NWO-VIDI 452.16.012//Nederlandse Organisatie voor Wetenschappelijk Onderzoek/International ; }, mesh = {*Algorithms ; Computer Simulation ; Gene Ontology ; Humans ; Influenza Vaccines/immunology ; Least-Squares Analysis ; Principal Component Analysis ; Regression Analysis ; Selection, Genetic ; Systems Biology ; }, abstract = {BACKGROUND: Data analysis methods are usually subdivided in two distinct classes: There are methods for prediction and there are methods for exploration. In practice, however, there often is a need to learn from the data in both ways. For example, when predicting the antibody titers a few weeks after vaccination on the basis of genomewide mRNA transcription rates, also mechanistic insights about the effect of vaccinations on the immune system are sought. Principal covariates regression (PCovR) is a method that combines both purposes. Yet, it misses insightful representations of the data as these include all the variables.

RESULTS: Here, we propose a sparse extension of principal covariates regression such that the resulting solutions are based on an automatically selected subset of the variables. Our method is shown to outperform competing methods like sparse principal components regression and sparse partial least squares in a simulation study. Furthermore good performance of the method is illustrated on publicly available data including antibody titers and genomewide transcription rates for subjects vaccinated against the flu: the selected genes by sparse PCovR are higly enriched for immune related terms and the method predicts the titers for an independent test sample well. In comparison, no significantly enriched terms were found for the genes selected by sparse partial least squares and out-of-sample prediction was worse.

CONCLUSIONS: Sparse principal covariates regression is a promising and competitive tool for obtaining insights from high-dimensional data.

AVAILABILITY: The source code implementing our proposed method is available from GitHub, together with all scripts used to extract, pre-process, analyze, and post-process the data: https://github.com/katrijnvandeun/SPCovR .}, } @article {pmid29587626, year = {2018}, author = {Schuler, H and Egan, SP and Hood, GR and Busbee, RW and Driscoe, AL and Ott, JR}, title = {Diversity and distribution of Wolbachia in relation to geography, host plant affiliation and life cycle of a heterogonic gall wasp.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {37}, pmid = {29587626}, issn = {1471-2148}, support = {J-3527-B22//Austrian Science Fund/International ; }, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; Female ; *Genetic Variation ; Genetics, Population ; *Geography ; Haplotypes/genetics ; *Life Cycle Stages ; Male ; Phylogeny ; Quercus/*parasitology ; United States ; Wasps/*genetics/*microbiology ; Wolbachia/genetics/*growth & development ; }, abstract = {BACKGROUND: The maternally inherited endosymbiont Wolbachia is widespread in arthropods and nematodes and can play an important role in the ecology and evolution of its host through reproductive manipulation. Here, we survey Wolbachia in Belonocnema treatae, a widely distributed North American cynipid gall forming wasp that exhibits regional host specialization on three species of oaks and alternation of sexually and asexually reproducing generations. We investigated whether patterns of Wolbachia infection and diversity in B. treatae are associated with the insect's geographic distribution, host plant association, life cycle, and mitochondrial evolutionary history.

RESULTS: Screening of 463 individuals from 23 populations including sexual and asexual generations from all three host plants across the southern U.S. showed an average infection rate of 56% with three common Wolbachia strains: wTre1-3 and an additional rare variant wTre4. Phylogenetic analysis based on wsp showed that these strains are unrelated and likely independently inherited. We found no difference in Wolbachia infection frequency among host plant associated populations or between the asexual and sexual generations, or between males and females of the sexual generation. Partially incomplete Wolbachia transmission rates might explain the occurrence of uninfected individuals. A parallel analysis of the mitochondrial cytochrome oxidase I gene in B. treatae showed high mtDNA haplotype diversity in both infected and uninfected populations suggesting an ancestral infection by Wolbachia as well as a clear split between eastern and western B. treatae mtDNA clades with a sequence divergence of > 6%. The strain wTre1 was present almost exclusively in the western clade while wTre2 and wTre3 occur almost exclusively in eastern populations. In contrast, the same strains co-occur as double-infections in Georgia and triple-infections in two populations in central Florida.

CONCLUSIONS: The diversity of Wolbachia across geographically and genetically distinct populations of B. treatae and the co-occurrence of the same strains within three populations highlights the complex infection dynamics in this system. Moreover, the association of distinct Wolbachia strains with mitochondrial haplotypes of its host in populations infected by different Wolbachia strains suggests a potential role of the endosymbiont in reproductive isolation in B. treatae.}, } @article {pmid29587624, year = {2018}, author = {Chen, P and Pan, C}, title = {Diabetes classification model based on boosting algorithms.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {109}, pmid = {29587624}, issn = {1471-2105}, mesh = {*Algorithms ; Diabetes Mellitus/*classification ; Humans ; *Models, Theoretical ; ROC Curve ; }, abstract = {BACKGROUND: Diabetes mellitus is a common and complicated chronic lifelong disease. Hence, it is of high clinical significance to find the most relevant clinical indexes and to perform efficient computer-aided pre-diagnoses and diagnoses.

RESULTS: Non-parametric statistical testing is performed on hundreds of medical measurement index results between diabetic and non-diabetic populations. Two common boosting algorithms, Adaboost.M1 and LogitBoost, are selected to establish a machine model for diabetes diagnosis based on these clinical test data, involving a total of 35,669 individuals. The machine classification models built by these two algorithms have very good classification ability. Here, the LogitBoost classification model is slightly better than the Adaboost.M1 classification model. The overall accuracy of the LogitBoost classification model reached 95.30% when using 10-fold cross validation. The true positive, true negative, false positive, and false negative rates of the binary classification model were 0.921, 0.969, 0.031, and 0.079, respectively, and the area under the receiver operating characteristic curve reached 0.99.

CONCLUSIONS: The boosting algorithms show excellent performance for the diabetes classification models based on clinical medical data. The coefficient matrix of the original data is a sparse matrix, because some of the test results were missing, including some that were directly related to disease diagnosis. Therefore, the model is robust and has a degree of pre-diagnosis function. In the process of selecting the preferred test items, the most statistically significant discriminating factors between the diabetic and general populations were obtained and can be used as reference risk factors for diabetes mellitus.}, } @article {pmid29583116, year = {2018}, author = {Yuk, KJ and Kim, YT and Huh, CS and Lee, JH}, title = {Lelliottia jeotgali sp. nov., isolated from a traditional Korean fermented clam.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1725-1731}, doi = {10.1099/ijsem.0.002737}, pmid = {29583116}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Bivalvia/*microbiology ; DNA, Bacterial/genetics ; Enterobacter/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Fermented Foods/*microbiology ; Genes, Bacterial ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seafood/*microbiology ; Sequence Analysis, DNA ; }, abstract = {Strain PFL01T was isolated from traditional Korean fermented clam, jogae-jeotgal, and characterized. The strain was a facultative anaerobic, Gram-stain-negative bacterium that was rod-shaped, motile and beige-pigmented. The phylogenetic sequence analysis based on the 16S rRNA gene from PFL01T revealed that it was closely related to Lelliottia nimipressuralis LMG 10245T and Lelliottia amnigena LMG 2784T with 99.3 and 99.3 % sequence identities, respectively. Multilocus sequence type analysis of concatenated partial aptD, gyrB, infB and rpoB gene sequences showed a clear distinction of strain PFL01T from its closest related type strains. The discrimination was also supported by unique repetitive extragenic palindromic PCR (Rep-PCR, ERIC-PCR) fingerprint patterns. In addition, results from average nucleotide identity analyses with other species were less than 85 %. vitek and API analyses revealed distinct characteristics from other species of Lelliottia. The cellular fatty acid profile of the strain consisted of C16 : 0, cyclo-C17 : 0, C16 : 1ω7c/C16 : 1ω6c and C18 : 1ω7c/C18 : 1ω6c as major components. The whole genome of PFL01T was 4.6 Mb with a G+C content of 55.3 mol%. Based on these results, strain PFL01T was classified as a novel species of the genus Lelliottia, for which the name Lelliottia jeotgali sp. nov. is proposed. The type strain in PFL01T (=KCCM 43247T=JCM 31901T).}, } @article {pmid29583112, year = {2018}, author = {Beltrán, D and Romo-Vaquero, M and Espín, JC and Tomás-Barberán, FA and Selma, MV}, title = {Ellagibacter isourolithinifaciens gen. nov., sp. nov., a new member of the family Eggerthellaceae, isolated from human gut.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1707-1712}, doi = {10.1099/ijsem.0.002735}, pmid = {29583112}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Adult ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid ; Fatty Acids/chemistry ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Glycolipids/chemistry ; Humans ; Male ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Urolithins are gut microbial metabolites that exert health benefits in vivo and are generated from ellagic acid (EA) and ellagitannin-containing foods such as strawberries, pomegranates and walnuts. Gordonibacter species produce some intermediary urolithins but the micro-organisms responsible for the transformation of EA into the final and more bioactive urolithins, such as urolithin A and isourolithin A, are unknown. We report here a new bacterium, capable of metabolizing EA into isourolithin A, isolated from healthy human faeces and characterized by determining phenotypic, biochemical and molecular methods. Strain CEBAS 4A belongs to the Eggerthellaceae family and differed from other genera of this family, both phylogenetically and phenotypically. Based on 16S rRNA gene sequence similarity, the strain was related to Enterorhabdus musicola DSM 19490T (92.9 % similarity), Enterorhabdus caecimuris DSM 21839T (92.7 % similarity), Adlercreutzia equolifaciens DSM 19450T (92.5 % similarity), Asaccharobacter celatus DSM 18785T (92.5 % similarity) and Parvibacter caecicola DSM 22242T (91.2 % similarity). This strain was strictly anaerobic and Gram-stain-positive. The whole-cell fatty acids were saturated (98.3 %), a very high percentage that differs from the nearest genera ranging from 62 to 73 %. The major respiratory lipoquinone was menaquinone-7 and the diamino acid in the peptidoglycan was meso-diaminopimelic acid. Diphosphatidylglycerol and phosphatidylglycerol comprised the main polar lipid profile in addition to several phosphoglycolipids (PGL1-2), phospholipids (PL1-4), glycolipids (GL1-6) and lipids. Based on these data, a new genus, Ellagibacter gen. nov. is proposed with one species, Ellagibacter isourolithinifaciens sp. nov. The type strain of Ellagibacter isourolithinifaciens is CEBAS 4AT (=DSM 104140T=CCUG 70284T).}, } @article {pmid29582094, year = {2018}, author = {Peng, ZF and Gao, DS and Yang, X and Liu, HY and Huangfu, HP and Wang, CQ}, title = {BlaOXA-10 and PSE-1 Genes Located on Class 1 Integrons in Gallibacterium anatis.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1477-1}, pmid = {29582094}, issn = {1432-0991}, support = {U1404328//National Natural Science Foundation of China grant/ ; 162300410153//Natural Science Foundation of HeNan grants Natural Science Foundation of HeNan grants/ ; HUAHE2015014//Science and Technology Innovation Team Project of Henan University of Animal Husbandry and Economy grants/ ; }, } @article {pmid29581591, year = {2018}, author = {Hendy, J and Welker, F and Demarchi, B and Speller, C and Warinner, C and Collins, MJ}, title = {A guide to ancient protein studies.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {791-799}, doi = {10.1038/s41559-018-0510-x}, pmid = {29581591}, issn = {2397-334X}, abstract = {Palaeoproteomics is an emerging neologism used to describe the application of mass spectrometry-based approaches to the study of ancient proteomes. As with palaeogenomics (the study of ancient DNA), it intersects evolutionary biology, archaeology and anthropology, with applications ranging from the phylogenetic reconstruction of extinct species to the investigation of past human diets and ancient diseases. However, there is no explicit consensus at present regarding standards for data reporting, data validation measures or the use of suitable contamination controls in ancient protein studies. Additionally, in contrast to the ancient DNA community, no consolidated guidelines have been proposed by which researchers, reviewers and editors can evaluate palaeoproteomics data, in part due to the novelty of the field. Here we present a series of precautions and standards for ancient protein research that can be implemented at each stage of analysis, from sample selection to data interpretation. These guidelines are not intended to impose a narrow or rigid list of authentication criteria, but rather to support good practices in the field and to ensure the generation of robust, reproducible results. As the field grows and methodologies change, so too will best practices. It is therefore essential that researchers continue to provide necessary details on how data were generated and authenticated so that the results can be independently and effectively evaluated. We hope that these proposed standards of practice will help to provide a firm foundation for the establishment of palaeoproteomics as a viable and powerful tool for archaeologists, anthropologists and evolutionary biologists.}, } @article {pmid29581590, year = {2018}, author = {Aronson, JC and Simberloff, D and Ricciardi, A and Goodwin, N}, title = {Restoration science does not need redefinition.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {916}, doi = {10.1038/s41559-018-0536-0}, pmid = {29581590}, issn = {2397-334X}, } @article {pmid29581589, year = {2018}, author = {Blockley, S and Candy, I and Matthews, I and Langdon, P and Langdon, C and Palmer, A and Lincoln, P and Abrook, A and Taylor, B and Conneller, C and Bayliss, A and MacLeod, A and Deeprose, L and Darvill, C and Kearney, R and Beavan, N and Staff, R and Bamforth, M and Taylor, M and Milner, N}, title = {The resilience of postglacial hunter-gatherers to abrupt climate change.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {810-818}, doi = {10.1038/s41559-018-0508-4}, pmid = {29581589}, issn = {2397-334X}, abstract = {Understanding the resilience of early societies to climate change is an essential part of exploring the environmental sensitivity of human populations. There is significant interest in the role of abrupt climate events as a driver of early Holocene human activity, but there are very few well-dated records directly compared with local climate archives. Here, we present evidence from the internationally important Mesolithic site of Star Carr showing occupation during the early Holocene, which is directly compared with a high-resolution palaeoclimate record from neighbouring lake beds. We show that-once established-there was intensive human activity at the site for several hundred years when the community was subject to multiple, severe, abrupt climate events that impacted air temperatures, the landscape and the ecosystem of the region. However, these results show that occupation and activity at the site persisted regardless of the environmental stresses experienced by this society. The Star Carr population displayed a high level of resilience to climate change, suggesting that postglacial populations were not necessarily held hostage to the flickering switch of climate change. Instead, we show that local, intrinsic changes in the wetland environment were more significant in determining human activity than the large-scale abrupt early Holocene climate events.}, } @article {pmid29581588, year = {2018}, author = {Jetz, W and Pyron, RA}, title = {The interplay of past diversification and evolutionary isolation with present imperilment across the amphibian tree of life.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {850-858}, doi = {10.1038/s41559-018-0515-5}, pmid = {29581588}, issn = {2397-334X}, abstract = {Human activities continue to erode the tree of life, requiring us to prioritize research and conservation. Amphibians represent key victims and bellwethers of global change, and the need for action to conserve them is drastically outpacing knowledge. We provide a phylogeny incorporating nearly all extant amphibians (7,238 species). Current amphibian diversity is composed of both older, depauperate lineages and extensive, more recent tropical radiations found in select clades. Frog and salamander diversification increased strongly after the Cretaceous-Palaeogene boundary, preceded by a potential mass-extinction event in salamanders. Diversification rates of subterranean caecilians varied little over time. Biogeographically, the Afro- and Neotropics harbour a particularly high proportion of Gondwanan relicts, comprising species with high evolutionary distinctiveness (ED). These high-ED species represent a large portion of the branches in the present tree: around 28% of all phylogenetic diversity comes from species in the top 10% of ED. The association between ED and imperilment is weak, but many species with high ED are now imperilled or lack formal threat status, suggesting opportunities for integrating evolutionary position and phylogenetic heritage in addressing the current extinction crisis. By providing a phylogenetic estimate for extant amphibians and identifying their threats and ED, we offer a preliminary basis for a quantitatively informed global approach to conserving the amphibian tree of life.}, } @article {pmid29581587, year = {2018}, author = {Driscoll, DA and Bland, LM and Bryan, BA and Newsome, TM and Nicholson, E and Ritchie, EG and Doherty, TS}, title = {A biodiversity-crisis hierarchy to evaluate and refine conservation indicators.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {775-781}, doi = {10.1038/s41559-018-0504-8}, pmid = {29581587}, issn = {2397-334X}, abstract = {The Convention on Biological Diversity and its Strategic Plan for Biodiversity 2011-2020 form the central pillar of the world's conservation commitment, with 196 signatory nations; yet its capacity to reign in catastrophic biodiversity loss has proved inadequate. Indicators suggest that few of the Convention on Biological Diversity's Aichi targets that aim to reduce biodiversity loss will be met by 2020. While the indicators have been criticized for only partially representing the targets, a bigger problem is that the indicators do not adequately draw attention to and measure all of the drivers of the biodiversity crisis. Here, we show that many key drivers of biodiversity loss are either poorly evaluated or entirely lacking indicators. We use a biodiversity-crisis hierarchy as a conceptual model linking drivers of change to biodiversity loss to evaluate the scope of current indicators. We find major gaps related to monitoring governments, human population size, corruption and threat-industries. We recommend the hierarchy is used to develop an expanded set of indicators that comprehensively monitor the human behaviour and institutions that drive biodiversity loss and that, so far, have impeded progress towards achieving global biodiversity targets.}, } @article {pmid29581586, year = {2018}, author = {Marad, DA and Buskirk, SW and Lang, GI}, title = {Altered access to beneficial mutations slows adaptation and biases fixed mutations in diploids.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {882-889}, doi = {10.1038/s41559-018-0503-9}, pmid = {29581586}, issn = {2397-334X}, abstract = {Ploidy varies considerably in nature. However, our understanding of the impact of ploidy on adaptation is incomplete. Many microbial evolution experiments characterize adaptation in haploid organisms, but few focus on diploid organisms. Here, we perform a 4,000-generation evolution experiment using diploid strains of the yeast Saccharomyces cerevisiae. We show that the rate of adaptation and spectrum of beneficial mutations are influenced by ploidy. Haldane's sieve effectively alters access to recessive beneficial mutations in diploid populations, leading to a slower rate of adaptation and a spectrum of beneficial mutations that is shifted towards dominant mutations. Genomic position also has an important role, as the prevalence of homozygous mutations is largely dependent on their proximity to a recombination hotspot. Our results demonstrate key aspects of diploid adaptation that have previously been understudied and provide support for several proposed theories.}, } @article {pmid29581404, year = {2018}, author = {Torney, CJ and Lamont, M and Debell, L and Angohiatok, RJ and Leclerc, LM and Berdahl, AM}, title = {Inferring the rules of social interaction in migrating caribou.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581404}, issn = {1471-2970}, abstract = {Social interactions are a significant factor that influence the decision-making of species ranging from humans to bacteria. In the context of animal migration, social interactions may lead to improved decision-making, greater ability to respond to environmental cues, and the cultural transmission of optimal routes. Despite their significance, the precise nature of social interactions in migrating species remains largely unknown. Here we deploy unmanned aerial systems to collect aerial footage of caribou as they undertake their migration from Victoria Island to mainland Canada. Through a Bayesian analysis of trajectories we reveal the fine-scale interaction rules of migrating caribou and show they are attracted to one another and copy directional choices of neighbours, but do not interact through clearly defined metric or topological interaction ranges. By explicitly considering the role of social information on movement decisions we construct a map of near neighbour influence that quantifies the nature of information flow in these herds. These results will inform more realistic, mechanism-based models of migration in caribou and other social ungulates, leading to better predictions of spatial use patterns and responses to changing environmental conditions. Moreover, we anticipate that the protocol we developed here will be broadly applicable to study social behaviour in a wide range of migratory and non-migratory taxa.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581403, year = {2018}, author = {Sasaki, T and Mann, RP and Warren, KN and Herbert, T and Wilson, T and Biro, D}, title = {Personality and the collective: bold homing pigeons occupy higher leadership ranks in flocks.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581403}, issn = {1471-2970}, abstract = {While collective movement is ecologically widespread and conveys numerous benefits on individuals, it also poses a coordination problem: who controls the group's movements? The role that animal 'personalities' play in this question has recently become a focus of research interest. Although many animal groups have distributed leadership (i.e. multiple individuals influence collective decisions), studies linking personality and leadership have focused predominantly on the group's single most influential individual. In this study, we investigate the relationship between personality and the influence of multiple leaders on collective movement using homing pigeons, Columba livia, a species known to display complex multilevel leadership hierarchies during flock flights. Our results show that more exploratory (i.e. 'bold') birds are more likely to occupy higher ranks in the leadership hierarchy and thus have more influence on the direction of collective movement than less exploratory (i.e. 'shy') birds during both free flights around their lofts and homing flights from a distant site. Our data also show that bold pigeons fly faster than shy birds during solo flights. We discuss our results in light of theories about the evolution of personality, with specific reference to the adaptive value of heterogeneity in animal groups.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581402, year = {2018}, author = {Yeakel, JD and Gibert, JP and Gross, T and Westley, PAH and Moore, JW}, title = {Eco-evolutionary dynamics, density-dependent dispersal and collective behaviour: implications for salmon metapopulation robustness.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581402}, issn = {1471-2970}, abstract = {The spatial dispersal of individuals plays an important role in the dynamics of populations, and is central to metapopulation theory. Dispersal provides connections within metapopulations, promoting demographic and evolutionary rescue, but may also introduce maladapted individuals, potentially lowering the fitness of recipient populations through introgression of heritable traits. To explore this dual nature of dispersal, we modify a well-established eco-evolutionary model of two locally adapted populations and their associated mean trait values, to examine recruiting salmon populations that are connected by density-dependent dispersal, consistent with collective migratory behaviour that promotes navigation. When the strength of collective behaviour is weak such that straying is effectively constant, we show that a low level of straying is associated with the highest gains in metapopulation robustness and that high straying serves to erode robustness. Moreover, we find that as the strength of collective behaviour increases, metapopulation robustness is enhanced, but this relationship depends on the rate at which individuals stray. Specifically, strong collective behaviour increases the presence of hidden low-density basins of attraction, which may serve to trap disturbed populations, and this is exacerbated by increased habitat heterogeneity. Taken as a whole, our findings suggest that density-dependent straying and collective migratory behaviour may help metapopulations, such as in salmon, thrive in dynamic landscapes. Given the pervasive eco-evolutionary impacts of dispersal on metapopulations, these findings have important ramifications for the conservation of salmon metapopulations facing both natural and anthropogenic contemporary disturbances.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581401, year = {2018}, author = {Hardesty-Moore, M and Deinet, S and Freeman, R and Titcomb, GC and Dillon, EM and Stears, K and Klope, M and Bui, A and Orr, D and Young, HS and Miller-Ter Kuile, A and Hughey, LF and McCauley, DJ}, title = {Migration in the Anthropocene: how collective navigation, environmental system and taxonomy shape the vulnerability of migratory species.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581401}, issn = {1471-2970}, abstract = {Recent increases in human disturbance pose significant threats to migratory species using collective movement strategies. Key threats to migrants may differ depending on behavioural traits (e.g. collective navigation), taxonomy and the environmental system (i.e. freshwater, marine or terrestrial) associated with migration. We quantitatively assess how collective navigation, taxonomic membership and environmental system impact species' vulnerability by (i) evaluating population change in migratory and non-migratory bird, mammal and fish species using the Living Planet Database (LPD), (ii) analysing the role of collective navigation and environmental system on migrant extinction risk using International Union for Conservation of Nature (IUCN) classifications and (iii) compiling literature on geographical range change of migratory species. Likelihood of population decrease differed by taxonomic group: migratory birds were more likely to experience annual declines than non-migrants, while mammals displayed the opposite pattern. Within migratory species in IUCN, we observed that collective navigation and environmental system were important predictors of extinction risk for fishes and birds, but not for mammals, which had overall higher extinction risk than other taxa. We found high phylogenetic relatedness among collectively navigating species, which could have obscured its importance in determining extinction risk. Overall, outputs from these analyses can help guide strategic interventions to conserve the most vulnerable migrations.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581400, year = {2018}, author = {Sumpter, DJT and Szorkovszky, A and Kotrschal, A and Kolm, N and Herbert-Read, JE}, title = {Using activity and sociability to characterize collective motion.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581400}, issn = {1471-2970}, abstract = {A wide range of measurements can be made on the collective motion of groups, and the movement of individuals within them. These include, but are not limited to: group size, polarization, speed, turning speed, speed or directional correlations, and distances to near neighbours. From an ecological and evolutionary perspective, we would like to know which of these measurements capture biologically meaningful aspects of an animal's behaviour and contribute to its survival chances. Previous simulation studies have emphasized two main factors shaping individuals' behaviour in groups; attraction and alignment. Alignment responses appear to be important in transferring information between group members and providing synergistic benefits to group members. Likewise, attraction to conspecifics is thought to provide benefits through, for example, selfish herding. Here, we use a factor analysis on a wide range of simple measurements to identify two main axes of collective motion in guppies (Poecilia reticulata): (i) sociability, which corresponds to attraction (and to a lesser degree alignment) to neighbours, and (ii) activity, which combines alignment with directed movement. We show that for guppies, predation in a natural environment produces higher degrees of sociability and (in females) lower degrees of activity, while female guppies sorted for higher degrees of collective alignment have higher degrees of both sociability and activity. We suggest that the activity and sociability axes provide a useful framework for measuring the behaviour of animals in groups, allowing the comparison of individual and collective behaviours within and between species.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581399, year = {2018}, author = {Sridhar, H and Guttal, V}, title = {Friendship across species borders: factors that facilitate and constrain heterospecific sociality.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581399}, issn = {1471-2970}, abstract = {Our understanding of animal sociality is based almost entirely on single-species sociality. Heterospecific sociality, although documented in numerous taxa and contexts, remains at the margins of sociality research and is rarely investigated in conjunction with single-species sociality. This could be because heterospecific and single-species sociality are thought to be based on fundamentally different mechanisms. However, our literature survey shows that heterospecific sociality based on mechanisms similar to single-species sociality is reported from many taxa, contexts and for various benefits. Therefore, we propose a conceptual framework to understand conspecific versus heterospecific social partner choice. Previous attempts, which are all in the context of social information, model partner choice as a trade-off between information benefit and competition cost, along a single phenotypic distance axis. Our framework of partner choice considers both direct grouping benefits and information benefits, allows heterospecific and conspecific partners to differ in degree and qualitatively, and uses a multi-dimensional trait space analysis of costs (competition and activity matching) and benefits (relevance of partner and quality of partner). We conclude that social partner choice is best-viewed as a continuum: some social benefits are obtainable only from conspecifics, some only from dissimilar heterospecifics, while many are potentially obtainable from conspecifics and heterospecifics.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581398, year = {2018}, author = {Fryxell, JM and Berdahl, AM}, title = {Fitness trade-offs of group formation and movement by Thomson's gazelles in the Serengeti ecosystem.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581398}, issn = {1471-2970}, abstract = {Collective behaviours contributing to patterns of group formation and coordinated movement are common across many ecosystems and taxa. Their ubiquity is presumably due to altering interactions between individuals and their predators, resources and physical environment in ways that enhance individual fitness. On the other hand, fitness costs are also often associated with group formation. Modifications to these interactions have the potential to dramatically impact population-level processes, such as trophic interactions or patterns of space use in relation to abiotic environmental variation. In a wide variety of empirical systems and models, collective behaviour has been shown to enhance access to ephemeral patches of resources, reduce the risk of predation and reduce vulnerability to environmental fluctuation. Evolution of collective behaviour should accordingly depend on the advantages of collective behaviour weighed against the costs experienced at the individual level. As an illustrative case study, we consider the potential trade-offs on Malthusian fitness associated with patterns of group formation and movement by migratory Thomson's gazelles in the Serengeti ecosystem.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581397, year = {2018}, author = {Torney, CJ and Hopcraft, JGC and Morrison, TA and Couzin, ID and Levin, SA}, title = {From single steps to mass migration: the problem of scale in the movement ecology of the Serengeti wildebeest.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581397}, issn = {1471-2970}, abstract = {A central question in ecology is how to link processes that occur over different scales. The daily interactions of individual organisms ultimately determine community dynamics, population fluctuations and the functioning of entire ecosystems. Observations of these multiscale ecological processes are constrained by various technological, biological or logistical issues, and there are often vast discrepancies between the scale at which observation is possible and the scale of the question of interest. Animal movement is characterized by processes that act over multiple spatial and temporal scales. Second-by-second decisions accumulate to produce annual movement patterns. Individuals influence, and are influenced by, collective movement decisions, which then govern the spatial distribution of populations and the connectivity of meta-populations. While the field of movement ecology is experiencing unprecedented growth in the availability of movement data, there remain challenges in integrating observations with questions of ecological interest. In this article, we present the major challenges of addressing these issues within the context of the Serengeti wildebeest migration, a keystone ecological phenomena that crosses multiple scales of space, time and biological complexity.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581396, year = {2018}, author = {Nagy, M and Couzin, ID and Fiedler, W and Wikelski, M and Flack, A}, title = {Synchronization, coordination and collective sensing during thermalling flight of freely migrating white storks.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581396}, issn = {1471-2970}, abstract = {Exploring how flocks of soaring migrants manage to achieve and maintain coordination while exploiting thermal updrafts is important for understanding how collective movements can enhance the sensing of the surrounding environment. Here we examined the structural organization of a group of circling white storks (Ciconia ciconia) throughout their migratory journey from Germany to Spain. We analysed individual high-resolution GPS trajectories of storks during circling events, and evaluated each bird's flight behaviour in relation to its flock members. Within the flock, we identified subgroups that synchronize their movements and coordinate switches in their circling direction within thermals. These switches in direction can be initiated by any individual of the subgroup, irrespective of how advanced its relative vertical position is, and occur at specific horizontal locations within the thermal allowing the storks to remain within the thermal. Using the motion of all flock members, we were able to examine the dynamic variation of airflow within the thermals and to determine the specific environmental conditions surrounding the flock. With an increasing amount of high-resolution GPS tracking, we may soon be able to use these animals as distributed sensors providing us with a new means to obtain a detailed knowledge of our environment.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581395, year = {2018}, author = {Beekman, M and Oldroyd, BP}, title = {Different bees, different needs: how nest-site requirements have shaped the decision-making processes in homeless honeybees (Apis spp.).}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581395}, issn = {1471-2970}, abstract = {During reproductive swarming, a honeybee swarm needs to decide on a new nest site and then move to the chosen site collectively. Most studies of swarming and nest-site selection are based on one species, Apis mellifera Natural colonies of A. mellifera live in tree cavities. The quality of the cavity is critical to the survival of a swarm. Other honeybee species nest in the open, and have less strict nest-site requirements, such as the open-nesting dwarf honeybee Apis floreaApis florea builds a nest comprised of a single comb suspended from a twig. For a cavity-nesting species, there is only a limited number of potential nest sites that can be located by a swarm, because suitable sites are scarce. By contrast, for an open-nesting species, there is an abundance of equally suitable twigs. While the decision-making process of cavity-nesting bees is geared towards selecting the best site possible, open-nesting species need to coordinate collective movement towards areas with potential nest sites. Here, we argue that the nest-site selection processes of A. florea and A. mellifera have been shaped by each species' specific nest-site requirements. Both species use the same behavioural algorithm, tuned to allow each species to solve their species-specific problem.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581394, year = {2018}, author = {Berdahl, AM and Kao, AB and Flack, A and Westley, PAH and Codling, EA and Couzin, ID and Dell, AI and Biro, D}, title = {Collective animal navigation and migratory culture: from theoretical models to empirical evidence.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581394}, issn = {1471-2970}, abstract = {Animals often travel in groups, and their navigational decisions can be influenced by social interactions. Both theory and empirical observations suggest that such collective navigation can result in individuals improving their ability to find their way and could be one of the key benefits of sociality for these species. Here, we provide an overview of the potential mechanisms underlying collective navigation, review the known, and supposed, empirical evidence for such behaviour and highlight interesting directions for future research. We further explore how both social and collective learning during group navigation could lead to the accumulation of knowledge at the population level, resulting in the emergence of migratory culture.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581393, year = {2018}, author = {Del Mar Delgado, M and Miranda, M and Alvarez, SJ and Gurarie, E and Fagan, WF and Penteriani, V and di Virgilio, A and Morales, JM}, title = {The importance of individual variation in the dynamics of animal collective movements.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581393}, issn = {1471-2970}, abstract = {Animal collective movements are a key example of a system that links two clearly defined levels of organization: the individual and the group. Most models investigating collective movements have generated coherent collective behaviours without the inclusion of individual variability. However, new individual-based models, together with emerging empirical information, emphasize that within-group heterogeneity may strongly influence collective movement behaviour. Here we (i) review the empirical evidence for individual variation in animal collective movements, (ii) explore how theoretical investigations have represented individual heterogeneity when modelling collective movements and (iii) present a model to show how within-group heterogeneity influences the collective properties of a group. Our review underscores the need to consider variability at the level of the individual to improve our understanding of how individual decision rules lead to emergent movement patterns, and also to yield better quantitative predictions of collective behaviour.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581392, year = {2018}, author = {Calabrese, JM and Fleming, CH and Fagan, WF and Rimmler, M and Kaczensky, P and Bewick, S and Leimgruber, P and Mueller, T}, title = {Disentangling social interactions and environmental drivers in multi-individual wildlife tracking data.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581392}, issn = {1471-2970}, abstract = {While many animal species exhibit strong conspecific interactions, movement analyses of wildlife tracking datasets still largely focus on single individuals. Multi-individual wildlife tracking studies provide new opportunities to explore how individuals move relative to one another, but such datasets are frequently too sparse for the detailed, acceleration-based analytical methods typically employed in collective motion studies. Here, we address the methodological gap between wildlife tracking data and collective motion by developing a general method for quantifying movement correlation from sparsely sampled data. Unlike most existing techniques for studying the non-independence of individual movements with wildlife tracking data, our approach is derived from an analytically tractable stochastic model of correlated movement. Our approach partitions correlation into a deterministic tendency to move in the same direction termed 'drift correlation' and a stochastic component called 'diffusive correlation'. These components suggest the mechanisms that coordinate movements, with drift correlation indicating external influences, and diffusive correlation pointing to social interactions. We use two case studies to highlight the ability of our approach both to quantify correlated movements in tracking data and to suggest the mechanisms that generate the correlation. First, we use an abrupt change in movement correlation to pinpoint the onset of spring migration in barren-ground caribou. Second, we show how spatial proximity mediates intermittently correlated movements among khulans in the Gobi desert. We conclude by discussing the linkages of our approach to the theory of collective motion.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581391, year = {2018}, author = {Strandburg-Peshkin, A and Papageorgiou, D and Crofoot, MC and Farine, DR}, title = {Inferring influence and leadership in moving animal groups.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581391}, issn = {1471-2970}, abstract = {Collective decision-making is a daily occurrence in the lives of many group-living animals, and can have critical consequences for the fitness of individuals. Understanding how decisions are reached, including who has influence and the mechanisms by which information and preferences are integrated, has posed a fundamental challenge. Here, we provide a methodological framework for studying influence and leadership in groups. We propose that individuals have influence if their actions result in some behavioural change among their group-mates, and are leaders if they consistently influence others. We highlight three components of influence (influence instances, total influence and consistency of influence), which can be assessed at two levels (individual-to-individual and individual-to-group). We then review different methods, ranging from individual positioning within groups to information-theoretic approaches, by which influence has been operationally defined in empirical studies, as well as how such observations can be aggregated to give insight into the underlying decision-making process. We focus on the domain of collective movement, with a particular emphasis on methods that have recently been, or are being, developed to take advantage of simultaneous tracking data. We aim to provide a resource bringing together methodological tools currently available for studying leadership in moving animal groups, as well as to discuss the limitations of current methodologies and suggest productive avenues for future research.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581390, year = {2018}, author = {Hughey, LF and Hein, AM and Strandburg-Peshkin, A and Jensen, FH}, title = {Challenges and solutions for studying collective animal behaviour in the wild.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581390}, issn = {1471-2970}, abstract = {Mobile animal groups provide some of the most compelling examples of self-organization in the natural world. While field observations of songbird flocks wheeling in the sky or anchovy schools fleeing from predators have inspired considerable interest in the mechanics of collective motion, the challenge of simultaneously monitoring multiple animals in the field has historically limited our capacity to study collective behaviour of wild animal groups with precision. However, recent technological advancements now present exciting opportunities to overcome many of these limitations. Here we review existing methods used to collect data on the movements and interactions of multiple animals in a natural setting. We then survey emerging technologies that are poised to revolutionize the study of collective animal behaviour by extending the spatial and temporal scales of inquiry, increasing data volume and quality, and expediting the post-processing of raw data.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581389, year = {2018}, author = {Westley, PAH and Berdahl, AM and Torney, CJ and Biro, D}, title = {Collective movement in ecology: from emerging technologies to conservation and management.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1746}, pages = {}, pmid = {29581389}, issn = {1471-2970}, abstract = {Recent advances in technology and quantitative methods have led to the emergence of a new field of study that stands to link insights of researchers from two closely related, but often disconnected disciplines: movement ecology and collective animal behaviour. To date, the field of movement ecology has focused on elucidating the internal and external drivers of animal movement and the influence of movement on broader ecological processes. Typically, tracking and/or remote sensing technology is employed to study individual animals in natural conditions. By contrast, the field of collective behaviour has quantified the significant role social interactions play in the decision-making of animals within groups and, to date, has predominantly relied on controlled laboratory-based studies and theoretical models owing to the constraints of studying interacting animals in the field. This themed issue is intended to formalize the burgeoning field of collective movement ecology which integrates research from both movement ecology and collective behaviour. In this introductory paper, we set the stage for the issue by briefly examining the approaches and current status of research in these areas. Next, we outline the structure of the theme issue and describe the obstacles collective movement researchers face, from data acquisition in the field to analysis and problems of scale, and highlight the key contributions of the assembled papers. We finish by presenting research that links individual and broad-scale ecological and evolutionary processes to collective movement, and finally relate these concepts to emerging challenges for the management and conservation of animals on the move in a world that is increasingly impacted by human activity.This article is part of the theme issue 'Collective movement ecology'.}, } @article {pmid29581381, year = {2018}, author = {Ferrante, L and Fearnside, PM}, title = {Amazon sugar cane: A threat to the forest.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1476}, doi = {10.1126/science.aat4208}, pmid = {29581381}, issn = {1095-9203}, mesh = {Agriculture/*trends ; *Forests ; *Saccharum ; }, } @article {pmid29581313, year = {2018}, author = {Binder, S and Isbell, F and Polasky, S and Catford, JA and Tilman, D}, title = {Grassland biodiversity can pay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3876-3881}, pmid = {29581313}, issn = {1091-6490}, mesh = {Agriculture/*economics ; *Biodiversity ; Ecology/economics ; Ecosystem ; Grassland ; Models, Biological ; Poaceae/classification/*growth & development ; }, abstract = {The biodiversity-ecosystem functioning (BEF) literature provides strong evidence of the biophysical basis for the potential profitability of greater diversity but does not address questions of optimal management. BEF studies typically focus on the ecosystem outputs produced by randomly assembled communities that only differ in their biodiversity levels, measured by indices such as species richness. Landholders, however, do not randomly select species to plant; they choose particular species that collectively maximize profits. As such, their interest is not in comparing the average performance of randomly assembled communities at each level of biodiversity but rather comparing the best-performing communities at each diversity level. Assessing the best-performing mixture requires detailed accounting of species' identities and relative abundances. It also requires accounting for the financial cost of individual species' seeds, and the economic value of changes in the quality, quantity, and variability of the species' collective output-something that existing multifunctionality indices fail to do. This study presents an assessment approach that integrates the relevant factors into a single, coherent framework. It uses ecological production functions to inform an economic model consistent with the utility-maximizing decisions of a potentially risk-averse private landowner. We demonstrate the salience and applicability of the framework using data from an experimental grassland to estimate production relationships for hay and carbon storage. For that case, our results suggest that even a risk-neutral, profit-maximizing landowner would favor a highly diverse mix of species, with optimal species richness falling between the low levels currently found in commercial grasslands and the high levels found in natural grasslands.}, } @article {pmid29581312, year = {2018}, author = {Rizza, S and Cardaci, S and Montagna, C and Di Giacomo, G and De Zio, D and Bordi, M and Maiani, E and Campello, S and Borreca, A and Puca, AA and Stamler, JS and Cecconi, F and Filomeni, G}, title = {S-nitrosylation drives cell senescence and aging in mammals by controlling mitochondrial dynamics and mitophagy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3388-E3397}, pmid = {29581312}, issn = {1091-6490}, support = {P01 HL075443/HL/NHLBI NIH HHS/United States ; P01 HL128192/HL/NHLBI NIH HHS/United States ; R01 GM099921/GM/NIGMS NIH HHS/United States ; R01 HL126900/HL/NHLBI NIH HHS/United States ; }, mesh = {Aging/genetics/*metabolism ; Aldehyde Oxidoreductases/genetics/metabolism ; Animals ; Cellular Senescence ; Humans ; Mammals/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mitochondria/genetics/*metabolism ; *Mitochondrial Degradation ; *Mitochondrial Dynamics ; Nitric Oxide/metabolism ; Nitrosative Stress ; Protein Processing, Post-Translational ; S-Nitrosothiols/metabolism ; }, abstract = {S-nitrosylation, a prototypic redox-based posttranslational modification, is frequently dysregulated in disease. S-nitrosoglutathione reductase (GSNOR) regulates protein S-nitrosylation by functioning as a protein denitrosylase. Deficiency of GSNOR results in tumorigenesis and disrupts cellular homeostasis broadly, including metabolic, cardiovascular, and immune function. Here, we demonstrate that GSNOR expression decreases in primary cells undergoing senescence, as well as in mice and humans during their life span. In stark contrast, exceptionally long-lived individuals maintain GSNOR levels. We also show that GSNOR deficiency promotes mitochondrial nitrosative stress, including excessive S-nitrosylation of Drp1 and Parkin, thereby impairing mitochondrial dynamics and mitophagy. Our findings implicate GSNOR in mammalian longevity, suggest a molecular link between protein S-nitrosylation and mitochondria quality control in aging, and provide a redox-based perspective on aging with direct therapeutic implications.}, } @article {pmid29581311, year = {2018}, author = {Doolittle, WF and Inkpen, SA}, title = {Processes and patterns of interaction as units of selection: An introduction to ITSNTS thinking.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4006-4014}, pmid = {29581311}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; Animals ; Biological Variation, Individual ; Cell Lineage ; Ecology ; Gene Regulatory Networks ; Genes ; Genetic Linkage ; Genetic Variation ; *Genetics, Population ; Metaphysics ; Microbial Interactions ; Microbiota ; *Models, Genetic ; Plants/genetics ; Reproduction ; Selection, Genetic/*genetics ; Symbiosis/genetics ; }, abstract = {Many practicing biologists accept that nothing in their discipline makes sense except in the light of evolution, and that natural selection is evolution's principal sense-maker. But what natural selection actually is (a force or a statistical outcome, for example) and the levels of the biological hierarchy (genes, organisms, species, or even ecosystems) at which it operates directly are still actively disputed among philosophers and theoretical biologists. Most formulations of evolution by natural selection emphasize the differential reproduction of entities at one or the other of these levels. Some also recognize differential persistence, but in either case the focus is on lineages of material things: even species can be thought of as spatiotemporally restricted, if dispersed, physical beings. Few consider-as "units of selection" in their own right-the processes implemented by genes, cells, species, or communities. "It's the song not the singer" (ITSNTS) theory does that, also claiming that evolution by natural selection of processes is more easily understood and explained as differential persistence than as differential reproduction. ITSNTS was formulated as a response to the observation that the collective functions of microbial communities (the songs) are more stably conserved and ecologically relevant than are the taxa that implement them (the singers). It aims to serve as a useful corrective to claims that "holobionts" (microbes and their animal or plant hosts) are aggregate "units of selection," claims that often conflate meanings of that latter term. But ITSNS also seems broadly applicable, for example, to the evolution of global biogeochemical cycles and the definition of ecosystem function.}, } @article {pmid29581310, year = {2018}, author = {Smith-Moore, S and Neil, SJD and Fraefel, C and Linden, RM and Bollen, M and Rowe, HM and Henckaerts, E}, title = {Adeno-associated virus Rep proteins antagonize phosphatase PP1 to counteract KAP1 repression of the latent viral genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3529-E3538}, pmid = {29581310}, issn = {1091-6490}, support = {1001764//Medical Research Council/United Kingdom ; MR/N022890/1//Medical Research Council/United Kingdom ; }, mesh = {Cell Line ; DNA Replication/physiology ; DNA, Viral/genetics ; DNA-Binding Proteins/genetics/*metabolism ; Dependovirus/genetics/*metabolism ; Epigenesis, Genetic ; Genome, Viral ; HEK293 Cells ; HeLa Cells ; Humans ; Parvoviridae Infections/metabolism/virology ; Receptors, Neuropeptide Y/*antagonists & inhibitors/metabolism ; Tripartite Motif-Containing Protein 28/*metabolism ; Viral Proteins/genetics/*metabolism ; Virion/metabolism ; Virus Latency ; Virus Replication/physiology ; }, abstract = {Adeno-associated virus (AAV) is a small human Dependovirus whose low immunogenicity and capacity for long-term persistence have led to its widespread use as vector for gene therapy. Despite great recent successes in AAV-based gene therapy, further improvements in vector technology may be hindered by an inadequate understanding of various aspects of basic AAV biology. AAV is unique in that its replication is largely dependent on a helper virus and cellular factors. In the absence of helper virus coinfection, wild-type AAV establishes latency through mechanisms that are not yet fully understood. Challenging the currently held model for AAV latency, we show here that the corepressor Krüppel-associated box domain-associated protein 1 (KAP1) binds the latent AAV2 genome at the rep ORF, leading to trimethylation of AAV2-associated histone 3 lysine 9 and that the inactivation of KAP1 repression is necessary for AAV2 reactivation and replication. We identify a viral mechanism for the counteraction of KAP1 in which interference with the KAP1 phosphatase protein phosphatase 1 (PP1) by the AAV2 Rep proteins mediates enhanced phosphorylation of KAP1-S824 and thus relief from KAP1 repression. Furthermore, we show that this phenomenon involves recruitment of the NIPP1 (nuclear inhibitor of PP1)-PP1α holoenzyme to KAP1 in a manner dependent upon the NIPP1 FHA domain, identifying NIPP1 as an interaction partner for KAP1 and shedding light on the mechanism through which PP1 regulates cellular KAP1 activity.}, } @article {pmid29581309, year = {2018}, author = {Setton, EVW and Sharma, PP}, title = {Cooption of an appendage-patterning gene cassette in the head segmentation of arachnids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3491-E3500}, pmid = {29581309}, issn = {1091-6490}, mesh = {Animals ; Arachnida/genetics ; Biological Evolution ; Body Patterning/*genetics ; Evolution, Molecular ; Extremities/physiology ; Gene Expression Regulation, Developmental/genetics ; Homeodomain Proteins/genetics ; Kruppel-Like Transcription Factors/genetics/metabolism ; Phenotype ; RNA Interference ; Spiders/*genetics/metabolism ; Transcription Factors/genetics/metabolism ; Wnt1 Protein/*genetics ; Zinc Fingers ; }, abstract = {The jointed appendages of arthropods have facilitated the spectacular diversity and success of this phylum. Key to the regulation of appendage outgrowth is the Krüppel-like factor (KLF)/specificity protein (Sp) family of zinc finger transcription factors. In the fruit fly, Drosophila melanogaster, the Sp6-9 homolog is activated by Wnt-1/wingless (wg) and establishes ventral appendage (leg) fate. Subsequently, Sp6-9 maintains expression of the axial patterning gene Distal-less (Dll), which promotes limb outgrowth. Intriguingly, in spiders, Dll has been reported to have a derived role as a segmentation gap gene, but the evolutionary origin and regulation of this function are not understood because functional investigations of the appendage-patterning regulatory network are restricted to insects. We tested the evolutionary conservation of the ancestral appendage-patterning network of arthropods with a functional approach in the spider. RNAi-mediated knockdown of the spider Sp6-9 ortholog resulted in diminution or loss of Dll expression and truncation of appendages, as well as loss of the two body segments specified by the early Dll function. In reciprocal experiments, Dll is shown not to be required for Sp6-9 expression. Knockdown of arrow (Wnt-1 coreceptor) disrupted segmentation and appendage development but did not affect the early Sp6-9 expression domain. Ectopic appendages generated in the spider "abdomen" by knockdown of the Hox gene Antennapedia-1 (Antp-1) expressed Sp6-9 comparably to wild-type walking legs. Our results support (i) the evolutionary conservation of an appendage-patterning regulatory network that includes canonical Wnt signaling, Sp6-9, and Dll and (ii) the cooption of the Sp6-9/Dll regulatory cassette in arachnid head segmentation.}, } @article {pmid29581308, year = {2018}, author = {Wang, H and Liu, J and Yuet, KP and Hill, AJ and Sternberg, PW}, title = {Split cGAL, an intersectional strategy using a split intein for refined spatiotemporal transgene control in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3900-3905}, pmid = {29581308}, issn = {1091-6490}, support = {K99 GM126137/GM/NIGMS NIH HHS/United States ; R21 MH115454/MH/NIMH NIH HHS/United States ; T32 GM007616/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics/metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; DNA-Binding Proteins/*genetics/metabolism ; Fungal Proteins/*genetics/metabolism ; *Gene Expression Regulation ; *Inteins ; Neurons/metabolism ; Promoter Regions, Genetic ; Protein Splicing ; Saccharomyces/genetics ; *Transgenes ; }, abstract = {Bipartite expression systems, such as the GAL4-UAS system, allow fine manipulation of gene expression and are powerful tools for interrogating gene function. Recently, we established cGAL, a GAL4-based bipartite expression system for transgene control in Caenorhabditis elegans, where a single promoter dictates the expression pattern of a cGAL driver, which then binds target upstream activation sequences to drive expression of a downstream effector gene. Here, we report a split strategy for cGAL using the split intein gp41-1 for intersectional control of transgene expression. Split inteins are protein domains that associate, self-excise, and covalently ligate their flanking peptides together. We split the DNA binding domain and transcriptional activation domain of cGAL and fused them to the N terminal of gp41-1-N-intein and the C terminal of gp41-1-C-intein, respectively. In cells where both halves of cGAL are expressed, a functional cGAL driver is reconstituted via intein-mediated protein splicing. This reconstitution allows expression of the driver to be dictated by two promoters for refined spatial control or spatiotemporal control of transgene expression. We apply the split cGAL system to genetically access the single pair of MC neurons (previously inaccessible with a single promoter), and reveal an important role of protein kinase A in rhythmic pharyngeal pumping in C. elegans Thus, the split cGAL system gives researchers a greater degree of spatiotemporal control over transgene expression, and will be a valuable genetic tool in C. elegans for dissecting gene function with finer cell-specific resolution.}, } @article {pmid29581307, year = {2018}, author = {Goris, M and Magin, RS and Foyn, H and Myklebust, LM and Varland, S and Ree, R and Drazic, A and Bhambra, P and Støve, SI and Baumann, M and Haug, BE and Marmorstein, R and Arnesen, T}, title = {Structural determinants and cellular environment define processed actin as the sole substrate of the N-terminal acetyltransferase NAA80.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4405-4410}, pmid = {29581307}, issn = {1091-6490}, support = {R35 GM118090/GM/NIGMS NIH HHS/United States ; T32 GM071339/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetyltransferases/*chemistry ; Actins/chemistry ; Crystallography, X-Ray ; Enzyme Inhibitors/*chemistry ; Humans ; N-Terminal Acetyltransferases/*chemistry ; Saccharomyces cerevisiae/chemistry ; Saccharomyces cerevisiae Proteins/chemistry ; Structure-Activity Relationship ; }, abstract = {N-terminal (Nt) acetylation is a major protein modification catalyzed by N-terminal acetyltransferases (NATs). Methionine acidic N termini, including actin, are cotranslationally Nt acetylated by NatB in all eukaryotes, but animal actins containing acidic N termini, are additionally posttranslationally Nt acetylated by NAA80. Actin Nt acetylation was found to regulate cytoskeletal dynamics and motility, thus making NAA80 a potential target for cell migration regulation. In this work, we developed potent and selective bisubstrate inhibitors for NAA80 and determined the crystal structure of NAA80 in complex with such an inhibitor, revealing that NAA80 adopts a fold similar to other NAT enzymes but with a more open substrate binding region. Furthermore, in contrast to most other NATs, the substrate specificity of NAA80 is mainly derived through interactions between the enzyme and the acidic amino acids at positions 2 and 3 of the actin substrate and not residues 1 and 2. A yeast model revealed that ectopic expression of NAA80 in a strain lacking NatB activity partially restored Nt acetylation of NatB substrates, including yeast actin. Thus, NAA80 holds intrinsic capacity to posttranslationally Nt acetylate NatB-type substrates in vivo. In sum, the presence of a dominant cotranslational NatB in all eukaryotes, the specific posttranslational actin methionine removal in animals, and finally, the unique structural features of NAA80 leave only the processed actins as in vivo substrates of NAA80. Together, this study reveals the molecular and cellular basis of NAA80 Nt acetylation and provides a scaffold for development of inhibitors for the regulation of cytoskeletal properties.}, } @article {pmid29581306, year = {2018}, author = {Zhou, Y and Nwokonko, RM and Cai, X and Loktionova, NA and Abdulqadir, R and Xin, P and Niemeyer, BA and Wang, Y and Trebak, M and Gill, DL}, title = {Cross-linking of Orai1 channels by STIM proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3398-E3407}, pmid = {29581306}, issn = {1091-6490}, support = {F31 GM125376/GM/NIGMS NIH HHS/United States ; R01 GM109279/GM/NIGMS NIH HHS/United States ; R01 GM120783/GM/NIGMS NIH HHS/United States ; R01 HL097111/HL/NHLBI NIH HHS/United States ; }, mesh = {Calcium/metabolism ; Dimerization ; Endoplasmic Reticulum/chemistry/genetics/metabolism ; Humans ; Membrane Proteins/chemistry/genetics/metabolism ; Neoplasm Proteins/*chemistry/genetics/*metabolism ; ORAI1 Protein/*chemistry/genetics/*metabolism ; Protein Domains ; Stromal Interaction Molecule 1/*chemistry/genetics/*metabolism ; Stromal Interaction Molecule 2/*chemistry/genetics/*metabolism ; }, abstract = {The transmembrane docking of endoplasmic reticulum (ER) Ca2+-sensing STIM proteins with plasma membrane (PM) Orai Ca2+ channels is a critical but poorly understood step in Ca2+ signal generation. STIM1 protein dimers unfold to expose a discrete STIM-Orai activating region (SOAR1) that tethers and activates Orai1 channels within discrete ER-PM junctions. We reveal that each monomer within the SOAR dimer interacts independently with single Orai1 subunits to mediate cross-linking between Orai1 channels. Superresolution imaging and mobility measured by fluorescence recovery after photobleaching reveal that SOAR dimer cross-linking leads to substantial Orai1 channel clustering, resulting in increased efficacy and cooperativity of Orai1 channel function. A concatenated SOAR1 heterodimer containing one monomer point mutated at its critical Orai1 binding residue (F394H), although fully activating Orai channels, is completely defective in cross-linking Orai1 channels. Importantly, the naturally occurring STIM2 variant, STIM2.1, has an eight-amino acid insert in its SOAR unit that renders it functionally identical to the F394H mutant in SOAR1. Contrary to earlier predictions, the SOAR1-SOAR2.1 heterodimer fully activates Orai1 channels but prevents cross-linking and clustering of channels. Interestingly, combined expression of full-length STIM1 with STIM2.1 in a 5:1 ratio causes suppression of sustained agonist-induced Ca2+ oscillations and protects cells from Ca2+ overload, resulting from high agonist-induced Ca2+ release. Thus, STIM2.1 exerts a powerful regulatory effect on signal generation likely through preventing Orai1 channel cross-linking. Overall, STIM-mediated cross-linking of Orai1 channels is a hitherto unrecognized functional paradigm that likely provides an organizational microenvironment within ER-PM junctions with important functional impact on Ca2+ signal generation.}, } @article {pmid29581305, year = {2018}, author = {DuBose, AJ and Lichtenstein, ST and Petrash, NM and Erdos, MR and Gordon, LB and Collins, FS}, title = {Everolimus rescues multiple cellular defects in laminopathy-patient fibroblasts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4206-4211}, pmid = {29581305}, issn = {1091-6490}, mesh = {Biomarkers ; Cell Division/drug effects ; Cell Line ; Cell Nucleus/drug effects/ultrastructure ; Cellular Senescence/drug effects ; Everolimus/*pharmacology ; Fibroblasts/*drug effects ; Humans ; Lamin Type A/*deficiency/genetics ; Muscular Dystrophy, Emery-Dreifuss/*genetics/pathology ; Mutation ; Phosphorylation/drug effects ; Progeria/*genetics/pathology ; Protein Processing, Post-Translational/drug effects ; Ribosomal Protein S6/metabolism ; TOR Serine-Threonine Kinases/*antagonists & inhibitors ; Werner Syndrome/*genetics/pathology ; }, abstract = {LMNA encodes the A-type lamins that are part of the nuclear scaffold. Mutations in LMNA can cause a variety of disorders called laminopathies, including Hutchinson-Gilford progeria syndrome (HGPS), atypical Werner syndrome, and Emery-Dreifuss muscular dystrophy. Previous work has shown that treatment of HGPS cells with the mTOR inhibitor rapamycin or with the rapamycin analog everolimus corrects several of the phenotypes seen at the cellular level-at least in part by increasing autophagy and reducing the amount of progerin, the toxic form of lamin A that is overproduced in HGPS patients. Since other laminopathies also result in production of abnormal and potentially toxic lamin proteins, we hypothesized that everolimus would also be beneficial in those disorders. To test this, we applied everolimus to fibroblast cell lines from six laminopathy patients, each with a different mutation in LMNA Everolimus treatment increased proliferative ability and delayed senescence in all cell lines. In several cell lines, we observed that with treatment, there is a significant improvement in nuclear blebbing, which is a cellular hallmark of HGPS and other lamin disorders. These preclinical results suggest that everolimus might have clinical benefit for multiple laminopathy syndromes.}, } @article {pmid29581304, year = {2018}, author = {Flores, AR and Hatzenbuehler, ML and Gates, GJ}, title = {Identifying psychological responses of stigmatized groups to referendums.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3816-3821}, pmid = {29581304}, issn = {1091-6490}, mesh = {Adult ; Advertising as Topic ; Bisexuality ; Emotions ; Female ; Humans ; Male ; Marriage/psychology ; Public Opinion ; Sexual and Gender Minorities/*psychology ; Social Stigma ; Surveys and Questionnaires ; Transgender Persons/*psychology ; United States ; Young Adult ; }, abstract = {Public votes and referendums on the rights of marginalized communities are utilized in 27 states and occur with some regularity. However, research has only recently begun to examine the psychological consequences of these voter referendums for members of stigmatized groups, and a number of important questions remain regarding the internal validity and generalizability of the existing evidence. The current study advances this literature by combining survey data from a large probability-based sample conducted in 2012 [lesbian, gay, bisexual, and/or transgender (LGBT) n = 939; non-LGBT n = 31,067] with media market ad-buy data in states where marriage equality was on the ballot. Television media markets cross state boundaries, ensuring that there was an unintended group of people in 12 states who were exposed to the same-sex marriage discourse but who did not live in states with the voter referendum ("media market spillovers"). We take advantage of this unique data structure by comparing LGBT people in the media market spillovers to those residing in the same state but in nonspillover markets with no ad exposure. LGBT people are emotionally affected by these campaigns, and non-LGBT people are unaffected. LGBT people in markets with a cumulative total of 400 ads have a 34.0% greater probability of reporting stress than LGBT people not exposed to ads. Additionally, while the negative ads evoked sadness, positive ads evoked enjoyment and happiness. Thus, public votes on minority rights represent both a source of minority stress and resilience.}, } @article {pmid29581303, year = {2018}, author = {Toyama, Y and Kano, H and Mase, Y and Yokogawa, M and Osawa, M and Shimada, I}, title = {Structural basis for the ethanol action on G-protein-activated inwardly rectifying potassium channel 1 revealed by NMR spectroscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3858-3863}, pmid = {29581303}, issn = {1091-6490}, mesh = {Allosteric Regulation ; Animals ; Binding Sites ; Ethanol/chemistry/*metabolism ; G Protein-Coupled Inwardly-Rectifying Potassium Channels/*chemistry/*metabolism ; Kinetics ; Magnetic Resonance Spectroscopy ; Mice ; Protein Conformation ; Protein Domains ; }, abstract = {Ethanol consumption leads to a wide range of pharmacological effects by acting on the signaling proteins in the human nervous system, such as ion channels. Despite its familiarity and biological importance, very little is known about the molecular mechanisms underlying the ethanol action, due to extremely weak binding affinity and the dynamic nature of the ethanol interaction. In this research, we focused on the primary in vivo target of ethanol, G-protein-activated inwardly rectifying potassium channel (GIRK), which is responsible for the ethanol-induced analgesia. By utilizing solution NMR spectroscopy, we characterized the changes in the structure and dynamics of GIRK induced by ethanol binding. We demonstrated here that ethanol binds to GIRK with an apparent dissociation constant of 1.0 M and that the actual physiological binding site of ethanol is located on the cavity formed between the neighboring cytoplasmic regions of the GIRK tetramer. From the methyl-based NMR relaxation analyses, we revealed that ethanol activates GIRK by shifting the conformational equilibrium processes, which are responsible for the gating of GIRK, to stabilize an open conformation of the cytoplasmic ion gate. We suggest that the dynamic molecular mechanism of the ethanol-induced activation of GIRK represents a general model of the ethanol action on signaling proteins in the human nervous system.}, } @article {pmid29581302, year = {2018}, author = {Sherwood, AV and Frandsen, JK and Grundy, FJ and Henkin, TM}, title = {New tRNA contacts facilitate ligand binding in a Mycobacterium smegmatis T box riboswitch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3894-3899}, pmid = {29581302}, issn = {1091-6490}, support = {R01 GM047823/GM/NIGMS NIH HHS/United States ; T32 GM086252/GM/NIGMS NIH HHS/United States ; }, mesh = {Gene Expression Regulation, Bacterial ; Isoleucine-tRNA Ligase/chemistry/*genetics/metabolism ; Models, Molecular ; Mycobacterium smegmatis/chemistry/*genetics/metabolism ; Nucleic Acid Conformation ; RNA, Bacterial/*chemistry/genetics/metabolism ; RNA, Transfer/*chemistry/genetics/metabolism ; *Regulatory Elements, Transcriptional ; *Riboswitch ; }, abstract = {T box riboswitches are RNA regulatory elements widely used by organisms in the phyla Firmicutes and Actinobacteria to regulate expression of amino acid-related genes. Expression of T box family genes is down-regulated by transcription attenuation or inhibition of translation initiation in response to increased charging of the cognate tRNA. Three direct contacts with tRNA have been described; however, one of these contacts is absent in a subclass of T box RNAs and the roles of several structural domains conserved in most T box RNAs are unknown. In this study, structural elements of a Mycobacterium smegmatis ileS T box riboswitch variant with an Ultrashort (US) Stem I were sequentially deleted, which resulted in a progressive decrease in binding affinity for the tRNAIle ligand. Selective 2'-hydroxyl acylation analyzed by primer extension (SHAPE) revealed structural changes in conserved riboswitch domains upon interaction with the tRNA ligand. Cross-linking and mutational analyses identified two interaction sites, one between the S-turn element in Stem II and the T arm of tRNAIle and the other between the Stem IIA/B pseudoknot and the D loop of tRNAIle These newly identified RNA contacts add information about tRNA recognition by the T box riboswitch and demonstrate a role for the S-turn and pseudoknot elements, which resemble structural elements that are common in many cellular RNAs.}, } @article {pmid29581301, year = {2018}, author = {Piezunka, H and Lee, W and Haynes, R and Bothner, MS}, title = {Escalation of competition into conflict in competitive networks of Formula One drivers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3361-E3367}, pmid = {29581301}, issn = {1091-6490}, mesh = {Adult ; Age Factors ; Athletes/*psychology ; *Competitive Behavior ; Conflict (Psychology) ; Hostility ; Humans ; Male ; *Social Support ; Sports/*psychology ; Young Adult ; }, abstract = {This article investigates the factors that escalate competition into dangerous conflict. Recent sociological theorizing claims that such escalations are particularly likely in dyads of structurally equivalent people (i.e., actors who have the same relations with the same third parties). Using panel data on Formula One races from 1970 through 2014, we model the probability that two drivers collide on the racetrack (an observable trace of conflict) as a function of their structural equivalence in a dynamic network of competitive relationships. Our main hypothesis, that the likelihood of conflict rises with structural equivalence, receives empirical support. Our findings also show that the positive association between structural equivalence and conflict is neither merely a matter of contention for official position nor an artifact of inherently hostile parties spatially exposed to each other. Our analyses further reveal that this positive association is concentrated in a number of theoretically predictable conditions: among age-similar dyads, among stronger performers, in stable competitive networks, and in safe, rather than dangerous, weather conditions. Implications for future research on conflict, networks, and tournaments are discussed.}, } @article {pmid29581300, year = {2018}, author = {Bao, J and Qin, M and Mahaman, YAR and Zhang, B and Huang, F and Zeng, K and Xia, Y and Ke, D and Wang, Q and Liu, R and Wang, JZ and Ye, K and Wang, X}, title = {BACE1 SUMOylation increases its stability and escalates the protease activity in Alzheimer's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3954-3959}, pmid = {29581300}, issn = {1091-6490}, support = {RF1 AG051538/AG/NIA NIH HHS/United States ; }, mesh = {Alzheimer Disease/*enzymology/genetics/metabolism/psychology ; Amino Acid Motifs ; Amyloid Precursor Protein Secretases/*chemistry/genetics/*metabolism ; Amyloid beta-Peptides/genetics/metabolism/toxicity ; Animals ; Aspartic Acid Endopeptidases/*chemistry/genetics/*metabolism ; Cognition ; Disease Models, Animal ; Enzyme Stability ; Humans ; Mice ; Mice, Transgenic ; Sumoylation ; }, abstract = {Amyloid beta (Aβ) is a major pathological marker in Alzheimer's disease (AD), which is principally regulated by the rate-limiting β-secretase (i.e., BACE1) cleavage of amyloid precursor protein (APP). However, how BACE1 activity is posttranslationally regulated remains incompletely understood. Here, we show that BACE1 is predominantly SUMOylated at K501 residue, which escalates its protease activity and stability and subsequently increases Aβ production, leading to cognitive defect seen in the AD mouse model. Compared with a non-SUMOylated K501R mutant, injection of wild-type BACE1 significantly increases Aβ production and triggers cognitive dysfunction. Furthermore, overexpression of wild-type BACE1, but not non-SUMOylated K501R mutant, facilitates senile plaque formation and aggravates the cognitive deficit seen in the APP/PS1 AD mouse model. Together, our data strongly suggest that K501 SUMOylation on BACE1 plays a critical role in mediating its stability and enzymatic activity.}, } @article {pmid29581299, year = {2018}, author = {Huang, Q and Chen, L and Yang, L and Xie, X and Gan, L and Cleveland, JL and Chen, J}, title = {MDMX acidic domain inhibits p53 DNA binding in vivo and regulates tumorigenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3368-E3377}, pmid = {29581299}, issn = {1091-6490}, support = {P30 CA076292/CA/NCI NIH HHS/United States ; R01 CA076379/CA/NCI NIH HHS/United States ; R01 CA141244/CA/NCI NIH HHS/United States ; R01 CA186917/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinogenesis/genetics/*metabolism ; Cell Transformation, Neoplastic ; Female ; Genes, myc ; Humans ; Lymphoma/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Binding ; Protein Domains ; Proto-Oncogene Proteins c-mdm2/*chemistry/genetics/*metabolism ; Tumor Suppressor Protein p53/chemistry/genetics/*metabolism ; }, abstract = {The MDM2 homolog MDMX oncoprotein is indispensable for inhibition of p53 during normal embryonic development and malignant transformation, yet how MDMX harnesses p53 functions is unclear. In addition to a canonical N-terminal p53-binding domain, recent work suggests the central acidic domain of MDMX regulates p53 interaction through intramolecular mimicry and engages in second-site interaction with the p53 core domain in vitro. To test the physiological relevance of these interactions, we generated an MDMX knockin mouse having substitutions in a conserved WW motif necessary for these functions (W201S/W202G). Notably, MDMXSG cells have normal p53 level but increased p53 DNA binding and target gene expression, and rapidly senesce. In vivo, MDMXSG inhibits early-phase disease in Eµ-Myc transgenic mice but accelerates the onset of lethal lymphoma and shortens overall survival. Therefore, MDMX is an important regulator of p53 DNA binding, which complements the role of MDM2 in regulating p53 level. Furthermore, the results suggest that the WW motif has dual functions that regulate p53 and inhibit Myc-driven lymphomas independent of p53.}, } @article {pmid29581298, year = {2018}, author = {Payne, JL and Khalid, F and Wagner, A}, title = {RNA-mediated gene regulation is less evolvable than transcriptional regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3481-E3490}, pmid = {29581298}, issn = {1091-6490}, mesh = {Animals ; Binding Sites/genetics ; DNA/metabolism ; DNA-Binding Proteins/metabolism ; Drosophila/genetics ; Evolution, Molecular ; Gene Expression Regulation/*genetics/physiology ; Humans ; Mutation ; RNA/metabolism ; RNA Processing, Post-Transcriptional/*genetics ; RNA-Binding Proteins/metabolism ; Regulatory Sequences, Nucleic Acid ; Transcription Factors/*genetics/metabolism ; Transcription, Genetic/genetics ; }, abstract = {Much of gene regulation is carried out by proteins that bind DNA or RNA molecules at specific sequences. One class of such proteins is transcription factors, which bind short DNA sequences to regulate transcription. Another class is RNA binding proteins, which bind short RNA sequences to regulate RNA maturation, transport, and stability. Here, we study the robustness and evolvability of these regulatory mechanisms. To this end, we use experimental binding data from 172 human and fruit fly transcription factors and RNA binding proteins as well as human polymorphism data to study the evolution of binding sites in vivo. We find little difference between the robustness of regulatory protein-RNA interactions and transcription factor-DNA interactions to DNA mutations. In contrast, we find that RNA-mediated regulation is less evolvable than transcriptional regulation, because mutations are less likely to create interactions of an RNA molecule with a new RNA binding protein than they are to create interactions of a gene regulatory region with a new transcription factor. Our observations are consistent with the high level of conservation observed for interactions between RNA binding proteins and their target molecules as well as the evolutionary plasticity of regulatory regions bound by transcription factors. They may help explain why transcriptional regulation is implicated in many more evolutionary adaptations and innovations than RNA-mediated gene regulation.}, } @article {pmid29581297, year = {2018}, author = {Bugide, S and Green, MR and Wajapeyee, N}, title = {Inhibition of Enhancer of zeste homolog 2 (EZH2) induces natural killer cell-mediated eradication of hepatocellular carcinoma cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3509-E3518}, pmid = {29581297}, issn = {1091-6490}, support = {R01 CA200919/CA/NCI NIH HHS/United States ; R21 CA195077/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Carcinoma, Hepatocellular/*drug therapy/genetics/*immunology/pathology ; Cell Line, Tumor ; DNA (Cytosine-5-)-Methyltransferases/metabolism ; DNA Methylation ; Down-Regulation ; Enhancer of Zeste Homolog 2 Protein/*antagonists & inhibitors/genetics/immunology ; GPI-Linked Proteins/genetics/immunology ; Hep G2 Cells ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/immunology ; Killer Cells, Natural/*immunology ; Ligands ; Liver Neoplasms/*drug therapy/genetics/*immunology/pathology ; NK Cell Lectin-Like Receptor Subfamily K/metabolism ; Promoter Regions, Genetic ; Small Molecule Libraries/*pharmacology ; }, abstract = {Natural killer (NK) cell-mediated tumor cell eradication could inhibit tumor initiation and progression. However, the factors that regulate NK cell-mediated cancer cell eradication remain unclear. We determined that hepatocellular carcinoma (HCC) cells exhibit transcriptional down-regulation of NK group 2D (NKG2D) ligands and are largely resistant to NK cell-mediated eradication. Because the down-regulation of NKG2D ligands occurred at the transcriptional level, we tested 32 chemical inhibitors of epigenetic regulators for their ability to re-express NKG2D ligands and enhance HCC cell eradication by NK cells and found that Enhancer of zeste homolog 2 (EZH2) was a transcriptional repressor of NKG2D ligands. The inhibition of EZH2 by small-molecule inhibitors or genetic means enhanced HCC cell eradication by NK cells in a NKG2D ligand-dependent manner. Collectively, these results demonstrate that EZH2 inhibition enhances HCC eradication by NK cells and that EZH2 functions, in part, as an oncogene by inhibiting immune response.}, } @article {pmid29581296, year = {2018}, author = {Wei, J and Bera, TK and Liu, XF and Zhou, Q and Onda, M and Ho, M and Tai, CH and Pastan, I}, title = {Recombinant immunotoxins with albumin-binding domains have long half-lives and high antitumor activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3501-E3508}, pmid = {29581296}, issn = {1091-6490}, mesh = {Animals ; Bacterial Toxins/pharmacokinetics/pharmacology ; Cell Line, Tumor/drug effects ; Disease Models, Animal ; Exotoxins/pharmacokinetics/pharmacology ; Female ; GPI-Linked Proteins/drug effects ; Half-Life ; Humans ; Immunotoxins/immunology/*pharmacokinetics ; Leukemia/drug therapy ; Mice ; Mice, Nude ; Recombinant Fusion Proteins/metabolism ; Recombinant Proteins/metabolism ; Serum Albumin/metabolism/therapeutic use ; }, abstract = {Recombinant immunotoxins (RITs) are chimeric proteins consisting of a Fv that binds to a cancer cell and a portion of a protein toxin. One of these, Moxetumomab pasudotox, was shown to be effective in treating patients with some leukemias, where the cells are readily accessible to the RIT. However, their short half-life limits their efficacy in solid tumors, because penetration into the tumors is slow. Albumin and agents bound to albumin have a long half-life in the circulation. To increase the time tumor cells are exposed to RITs, we have produced and evaluated variants that contain either an albumin-binding domain (ABD) from Streptococcus or single-domain antibodies from Llama. We have inserted these ABDs into RITs targeting mesothelin, between the Fv and the furin cleavage site. We find that these proteins can be produced in large amounts, are very cytotoxic to mesothelin-expressing cancer cell lines, and have a high affinity for human or mouse serum albumin. In mice, the RIT containing an ABD from Streptococcus has a longer half-life and higher antitumor activity than the other two. Its half-life in the circulation of mice ranges from 113 to 194 min compared with 13 min for an RIT with no ABD. Cell uptake studies show the RIT enters the target cell bound to serum albumin. We conclude that RITs with improved half-lives and antitumor activity should be evaluated for the treatment of cancer in humans.}, } @article {pmid29581295, year = {2018}, author = {Dunkelmann, DL and Hirata, Y and Totaro, KA and Cohen, DT and Zhang, C and Gates, ZP and Pentelute, BL}, title = {Amide-forming chemical ligation via O-acyl hydroxamic acids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3752-3757}, pmid = {29581295}, issn = {1091-6490}, abstract = {The facile rearrangement of "S-acyl isopeptides" to native peptide bonds via S,N-acyl shift is central to the success of native chemical ligation, the widely used approach for protein total synthesis. Proximity-driven amide bond formation via acyl transfer reactions in other contexts has proven generally less effective. Here, we show that under neutral aqueous conditions, "O-acyl isopeptides" derived from hydroxy-asparagine [aspartic acid-β-hydroxamic acid; Asp(β-HA)] rearrange to form native peptide bonds via an O,N-acyl shift. This process constitutes a rare example of an O,N-acyl shift that proceeds rapidly across a medium-size ring (t1/2 ∼ 15 min), and takes place in water with minimal interference from hydrolysis. In contrast to serine/threonine or tyrosine, which form O-acyl isopeptides only by the use of highly activated acyl donors and appropriate protecting groups in organic solvent, Asp(β-HA) is sufficiently reactive to form O-acyl isopeptides by treatment with an unprotected peptide-αthioester, at low mM concentration, in water. These findings were applied to an acyl transfer-based chemical ligation strategy, in which an unprotected N-terminal Asp(β-HA)-peptide and peptide-αthioester react under aqueous conditions to give a ligation product ultimately linked by a native peptide bond.}, } @article {pmid29581294, year = {2018}, author = {Zhang, X and Wang, Q and Wu, J and Wang, J and Shi, Y and Liu, M}, title = {Crystal structure of human lysyl oxidase-like 2 (hLOXL2) in a precursor state.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3828-3833}, pmid = {29581294}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Amino Acid Oxidoreductases/*chemistry/metabolism ; Catalysis ; Copper/chemistry/metabolism ; Crystallography, X-Ray ; Humans ; Lysine/analogs & derivatives/chemistry/metabolism ; Quinones/chemistry/metabolism ; Zinc/chemistry/metabolism ; }, abstract = {Lysyl oxidases (LOXs), a type of copper- and lysyl tyrosylquinone (LTQ) -dependent amine oxidase, catalyze the oxidative deamination of lysine residues of extracellular matrix (ECM) proteins such as elastins and collagens and generate aldehyde groups. The oxidative deamination of lysine represents the foundational step for the cross-linking of elastin and collagen and thus is crucial for ECM modeling. Despite their physiological significance, the structure of this important family of enzymes remains elusive. Here we report the crystal structure of human lysyl oxidase-like 2 (hLOXL2) at 2.4-Å resolution. Unexpectedly, the copper-binding site of hLOXL2 is occupied by zinc, which blocks LTQ generation and the enzymatic activity of hLOXL2 in our in vitro assay. Biochemical analysis confirms that copper loading robustly activates hLOXL2 and supports LTQ formation. Furthermore, the LTQ precursor residues in the structure are distanced by 16.6 Å, corroborating the notion that the present structure may represent a precursor state and that pronounced conformational rearrangements would be required for protein activation. The structure presented here establishes an important foundation for understanding the structure-function relationship of LOX proteins and will facilitate LOX-targeting drug discovery.}, } @article {pmid29581293, year = {2018}, author = {Stríkis, NM and Cruz, FW and Barreto, EAS and Naughton, F and Vuille, M and Cheng, H and Voelker, AHL and Zhang, H and Karmann, I and Edwards, RL and Auler, AS and Santos, RV and Sales, HR}, title = {South American monsoon response to iceberg discharge in the North Atlantic.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3788-3793}, pmid = {29581293}, issn = {1091-6490}, mesh = {Climate ; *Cyclonic Storms ; Ice Cover/*chemistry ; Oxygen Isotopes/analysis ; Seawater/chemistry ; South America ; Temperature ; }, abstract = {Heinrich Stadials significantly affected tropical precipitation through changes in the interhemispheric temperature gradient as a result of abrupt cooling in the North Atlantic. Here, we focus on changes in South American monsoon precipitation during Heinrich Stadials using a suite of speleothem records covering the last 85 ky B.P. from eastern South America. We document the response of South American monsoon precipitation to episodes of extensive iceberg discharge, which is distinct from the response to the cooling episodes that precede the main phase of ice-rafted detritus deposition. Our results demonstrate that iceberg discharge in the western subtropical North Atlantic led to an abrupt increase in monsoon precipitation over eastern South America. Our findings of an enhanced Southern Hemisphere monsoon, coeval with the iceberg discharge into the North Atlantic, are consistent with the observed abrupt increase in atmospheric methane concentrations during Heinrich Stadials.}, } @article {pmid29581292, year = {2018}, author = {Staus, DP and Wingler, LM and Choi, M and Pani, B and Manglik, A and Kruse, AC and Lefkowitz, RJ}, title = {Sortase ligation enables homogeneous GPCR phosphorylation to reveal diversity in β-arrestin coupling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3834-3839}, pmid = {29581292}, issn = {1091-6490}, support = {R01 HL016037/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Allosteric Regulation ; Aminoacyltransferases/*metabolism ; Bacterial Proteins/*metabolism ; Cysteine Endopeptidases/*metabolism ; Humans ; Phosphorylation ; Receptor, Muscarinic M2/genetics/*metabolism ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; Receptors, G-Protein-Coupled/genetics/metabolism ; Receptors, Opioid, mu/genetics/*metabolism ; beta-Arrestin 1/genetics/*metabolism ; }, abstract = {The ability of G protein-coupled receptors (GPCRs) to initiate complex cascades of cellular signaling is governed by the sequential coupling of three main transducer proteins, G protein, GPCR kinase (GRK), and β-arrestin. Mounting evidence indicates these transducers all have distinct conformational preferences and binding modes. However, interrogating each transducer's mechanism of interaction with GPCRs has been complicated by the interplay of transducer-mediated signaling events. For example, GRK-mediated receptor phosphorylation recruits and induces conformational changes in β-arrestin, which facilitates coupling to the GPCR transmembrane core. Here we compare the allosteric interactions of G proteins and β-arrestins with GPCRs' transmembrane cores by using the enzyme sortase to ligate a synthetic phosphorylated peptide onto the carboxyl terminus of three different receptors. Phosphopeptide ligation onto the β2-adrenergic receptor (β2AR) allows stabilization of a high-affinity receptor active state by β-arrestin1, permitting us to define elements in the β2AR and β-arrestin1 that contribute to the receptor transmembrane core interaction. Interestingly, ligation of the identical phosphopeptide onto the β2AR, the muscarinic acetylcholine receptor 2 and the μ-opioid receptor reveals that the ability of β-arrestin1 to enhance agonist binding relative to G protein differs substantially among receptors. Furthermore, strong allosteric coupling of β-arrestin1 correlates with its ability to attenuate, or "desensitize," G protein activation in vitro. Sortase ligation thus provides a versatile method to introduce complex, defined phosphorylation patterns into GPCRs, and analogous strategies could be applied to other classes of posttranslationally modified proteins. These homogeneously phosphorylated GPCRs provide an innovative means to systematically study receptor-transducer interactions.}, } @article {pmid29581291, year = {2018}, author = {Zou, Z and Xiao, X and Dong, J and Qin, Y and Doughty, RB and Menarguez, MA and Zhang, G and Wang, J}, title = {Divergent trends of open-surface water body area in the contiguous United States from 1984 to 2016.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3810-3815}, pmid = {29581291}, issn = {1091-6490}, abstract = {The contiguous United States (CONUS), especially the West, faces challenges of increasing water stress and uncertain impacts of climate change. The historical information of surface water body distribution, variation, and multidecadal trends documented in remote-sensing images can aid in water-resource planning and management, yet is not well explored. Here, we detected open-surface water bodies in all Landsat 5, 7, and 8 images (∼370,000 images, >200 TB) of the CONUS and generated 30-meter annual water body frequency maps for 1984-2016. We analyzed the interannual variations and trends of year-long water body area, examined the impacts of climatic and anthropogenic drivers on water body area dynamics, and explored the relationships between water body area and land water storage (LWS). Generally, the western half of the United States is prone to water stress, with small water body area and large interannual variability. During 1984-2016, water-poor regions of the Southwest and Northwest had decreasing trends in water body area, while water-rich regions of the Southeast and far north Great Plains had increasing trends. These divergent trends, mainly driven by climate, enlarged water-resource gaps and are likely to continue according to climate projections. Water body area change is a good indicator of LWS dynamics in 58% of the CONUS. Following the 2012 prolonged drought, LWS in California and the southern Great Plains had a larger decrease than surface water body area, likely caused by massive groundwater withdrawals. Our findings provide valuable information for surface water-resource planning and management across the CONUS.}, } @article {pmid29581290, year = {2018}, author = {Taylor, CA and An, SW and Kankanamalage, SG and Stippec, S and Earnest, S and Trivedi, AT and Yang, JZ and Mirzaei, H and Huang, CL and Cobb, MH}, title = {OSR1 regulates a subset of inward rectifier potassium channels via a binding motif variant.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3840-3845}, pmid = {29581290}, issn = {1091-6490}, support = {P30 CA142543/CA/NCI NIH HHS/United States ; R01 DK111542/DK/NIDDK NIH HHS/United States ; R37 DK034128/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Sequence ; Humans ; Molecular Sequence Data ; Multigene Family ; Mutation ; Potassium Channels, Inwardly Rectifying/*chemistry/genetics/*metabolism ; Protein Domains ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Sequence Alignment ; Signal Transduction ; }, abstract = {The with-no-lysine (K) (WNK) signaling pathway to STE20/SPS1-related proline- and alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1) kinase is an important mediator of cell volume and ion transport. SPAK and OSR1 associate with upstream kinases WNK 1-4, substrates, and other proteins through their C-terminal domains which interact with linear R-F-x-V/I sequence motifs. In this study we find that SPAK and OSR1 also interact with similar affinity with a motif variant, R-x-F-x-V/I. Eight of 16 human inward rectifier K+ channels have an R-x-F-x-V motif. We demonstrate that two of these channels, Kir2.1 and Kir2.3, are activated by OSR1, while Kir4.1, which does not contain the motif, is not sensitive to changes in OSR1 or WNK activity. Mutation of the motif prevents activation of Kir2.3 by OSR1. Both siRNA knockdown of OSR1 and chemical inhibition of WNK activity disrupt NaCl-induced plasma membrane localization of Kir2.3. Our results suggest a mechanism by which WNK-OSR1 enhance Kir2.1 and Kir2.3 channel activity by increasing their plasma membrane localization. Regulation of members of the inward rectifier K+ channel family adds functional and mechanistic insight into the physiological impact of the WNK pathway.}, } @article {pmid29581289, year = {2018}, author = {Gearty, W and McClain, CR and Payne, JL}, title = {Energetic tradeoffs control the size distribution of aquatic mammals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4194-4199}, pmid = {29581289}, issn = {1091-6490}, mesh = {Animals ; Artiodactyla/anatomy & histology/physiology ; Basal Metabolism ; Biological Evolution ; Body Size/*physiology ; Body Temperature Regulation/physiology ; Caniformia/*anatomy & histology/metabolism ; Cetacea/*anatomy & histology/metabolism ; *Energy Metabolism ; Feeding Behavior ; Fossils ; Models, Biological ; Otters/*anatomy & histology/metabolism ; Phylogeny ; Sirenia/*anatomy & histology/metabolism ; Species Specificity ; Thermal Diffusion ; Water ; }, abstract = {Four extant lineages of mammals have invaded and diversified in the water: Sirenia, Cetacea, Pinnipedia, and Lutrinae. Most of these aquatic clades are larger bodied, on average, than their closest land-dwelling relatives, but the extent to which potential ecological, biomechanical, and physiological controls contributed to this pattern remains untested quantitatively. Here, we use previously published data on the body masses of 3,859 living and 2,999 fossil mammal species to examine the evolutionary trajectories of body size in aquatic mammals through both comparative phylogenetic analysis and examination of the fossil record. Both methods indicate that the evolution of an aquatic lifestyle is driving three of the four extant aquatic mammal clades toward a size attractor at ∼500 kg. The existence of this body size attractor and the relatively rapid selection toward, and limited deviation from, this attractor rule out most hypothesized drivers of size increase. These three independent body size increases and a shared aquatic optimum size are consistent with control by differences in the scaling of energetic intake and cost functions with body size between the terrestrial and aquatic realms. Under this energetic model, thermoregulatory costs constrain minimum size, whereas limitations on feeding efficiency constrain maximum size. The optimum size occurs at an intermediate value where thermoregulatory costs are low but feeding efficiency remains high. Rather than being released from size pressures, water-dwelling mammals are driven and confined to larger body sizes by the strict energetic demands of the aquatic medium.}, } @article {pmid29581288, year = {2018}, author = {Burke, RM and Lighthouse, JK and Quijada, P and Dirkx, RA and Rosenberg, A and Moravec, CS and Alexis, JD and Small, EM}, title = {Small proline-rich protein 2B drives stress-dependent p53 degradation and fibroblast proliferation in heart failure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3436-E3445}, pmid = {29581288}, issn = {1091-6490}, support = {F32 HL136066/HL/NHLBI NIH HHS/United States ; R01 HL133761/HL/NHLBI NIH HHS/United States ; R01 HL120919/HL/NHLBI NIH HHS/United States ; T32 HL007937/HL/NHLBI NIH HHS/United States ; F32 HL134206/HL/NHLBI NIH HHS/United States ; T32 HL066988/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Animals ; *Cell Proliferation ; Cornified Envelope Proline-Rich Proteins/genetics/*metabolism ; Fibroblasts/*metabolism ; Heart Failure/genetics/*metabolism/physiopathology ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Middle Aged ; Myocardium/metabolism ; Proteolysis ; Transforming Growth Factor beta1/genetics/metabolism ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Heart disease is associated with the accumulation of resident cardiac fibroblasts (CFs) that secrete extracellular matrix (ECM), leading to the development of pathological fibrosis and heart failure. However, the mechanisms underlying resident CF proliferation remain poorly defined. Here, we report that small proline-rich protein 2b (Sprr2b) is among the most up-regulated genes in CFs during heart disease. We demonstrate that SPRR2B is a regulatory subunit of the USP7/MDM2-containing ubiquitination complex. SPRR2B stimulates the accumulation of MDM2 and the degradation of p53, thus facilitating the proliferation of pathological CFs. Furthermore, SPRR2B phosphorylation by nonreceptor tyrosine kinases in response to TGF-β1 signaling and free-radical production potentiates SPRR2B activity and cell cycle progression. Knockdown of the Sprr2b gene or inhibition of SPRR2B phosphorylation attenuates USP7/MDM2 binding and p53 degradation, leading to CF cell cycle arrest. Importantly, SPRR2B expression is elevated in cardiac tissue from human heart failure patients and correlates with the proliferative state of patient-derived CFs in a process that is reversed by insulin growth factor-1 signaling. These data establish SPRR2B as a unique component of the USP7/MDM2 ubiquitination complex that drives p53 degradation, CF accumulation, and the development of pathological cardiac fibrosis.}, } @article {pmid29581287, year = {2018}, author = {Bi, P and McAnally, JR and Shelton, JM and Sánchez-Ortiz, E and Bassel-Duby, R and Olson, EN}, title = {Fusogenic micropeptide Myomixer is essential for satellite cell fusion and muscle regeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3864-3869}, pmid = {29581287}, issn = {1091-6490}, support = {R01 AR067294/AR/NIAMS NIH HHS/United States ; R01 HL130253/HL/NHLBI NIH HHS/United States ; U54 HD087351/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Fusion ; Female ; Male ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Muscle Proteins/genetics/metabolism ; Muscle, Skeletal/growth & development/injuries/metabolism/*physiopathology ; Regeneration ; Satellite Cells, Skeletal Muscle/cytology/*metabolism ; }, abstract = {Regeneration of skeletal muscle in response to injury occurs through fusion of a population of stem cells, known as satellite cells, with injured myofibers. Myomixer, a muscle-specific membrane micropeptide, cooperates with the transmembrane protein Myomaker to regulate embryonic myoblast fusion and muscle formation. To investigate the role of Myomixer in muscle regeneration, we used CRISPR/Cas9-mediated genome editing to generate conditional knockout Myomixer alleles in mice. We show that genetic deletion of Myomixer in satellite cells using a tamoxifen-regulated Cre recombinase transgene under control of the Pax7 promoter abolishes satellite cell fusion and prevents muscle regeneration, resulting in severe muscle degeneration after injury. Satellite cells devoid of Myomixer maintain expression of Myomaker, demonstrating that Myomaker alone is insufficient to drive myoblast fusion. These findings, together with prior studies demonstrating the essentiality of Myomaker for muscle regeneration, highlight the obligatory partnership of Myomixer and Myomaker for myofiber formation throughout embryogenesis and adulthood.}, } @article {pmid29581286, year = {2018}, author = {de Vries, J and Curtis, BA and Gould, SB and Archibald, JM}, title = {Embryophyte stress signaling evolved in the algal progenitors of land plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3471-E3480}, pmid = {29581286}, issn = {1091-6490}, mesh = {Biological Evolution ; Biological Phenomena ; Cell Communication/physiology ; Cell Nucleus/metabolism ; Charophyceae/metabolism ; Chlorophyta/metabolism ; Embryophyta/metabolism ; Evolution, Molecular ; Phylogeny ; Plants/metabolism ; Plastids/metabolism/physiology ; Streptophyta/*metabolism/physiology ; Stress, Physiological/*physiology ; }, abstract = {Streptophytes are unique among photosynthetic eukaryotes in having conquered land. As the ancestors of land plants, streptophyte algae are hypothesized to have possessed exaptations to the environmental stressors encountered during the transition to terrestrial life. Many of these stressors, including high irradiance and drought, are linked to plastid biology. We have investigated global gene expression patterns across all six major streptophyte algal lineages, analyzing a total of around 46,000 genes assembled from a little more than 1.64 billion sequence reads from six organisms under three growth conditions. Our results show that streptophyte algae respond to cold and high light stress via expression of hallmark genes used by land plants (embryophytes) during stress-response signaling and downstream responses. Among the strongest differentially regulated genes were those associated with plastid biology. We observed that among streptophyte algae, those most closely related to land plants, especially Zygnema, invest the largest fraction of their transcriptional budget in plastid-targeted proteins and possess an array of land plant-type plastid-nucleus communication genes. Streptophyte algae more closely related to land plants also appear most similar to land plants in their capacity to respond to plastid stressors. Support for this notion comes from the detection of a canonical abscisic acid receptor of the PYRABACTIN RESISTANCE (PYR/PYL/RCAR) family in Zygnema, the first found outside the land plant lineage. We conclude that a fine-tuned response toward terrestrial plastid stressors was among the exaptations that allowed streptophytes to colonize the terrestrial habitat on a global scale.}, } @article {pmid29581285, year = {2018}, author = {Setny, P and Wiśniewska, MD}, title = {Water-mediated conformational preselection mechanism in substrate binding cooperativity to protein kinase A.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3852-3857}, pmid = {29581285}, issn = {1091-6490}, mesh = {Allosteric Regulation ; Amino Acid Motifs ; Animals ; Binding Sites ; Biocatalysis ; Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/*chemistry/genetics/*metabolism ; Hydrogen Bonding ; Mice ; Molecular Dynamics Simulation ; Mutation ; Water/chemistry/*metabolism ; }, abstract = {Substrate binding cooperativity in protein kinase A (PKA) seems to involve allosteric coupling between the two binding sites. It received significant attention, but its molecular basis still remains not entirely clear. Based on long molecular dynamics of PKA and its complexes, we characterized an allosteric pathway that links ATP binding to the redistribution of states adopted by a protein substrate positioning segment in favor of those that warrant correct binding. We demonstrate that the cooperativity mechanism critically depends on the presence of water in two distinct, buried hydration sites. One holds just a single water molecule, which acts as a switchable hydrogen bond bridge along the allosteric pathway. The second, filled with partially disordered solvent, is essential for providing a smooth free energy landscape underlying conformational transitions of the peptide binding region. Our findings remain in agreement with experimental data, also concerning the cooperativity abolishing effect of the Y204A mutation, and indicate a plausible molecular mechanism contributing to experimentally observed binding cooperativity of the two substrates.}, } @article {pmid29581284, year = {2018}, author = {Zhang, Z and Remsing, RC and Chakraborty, H and Gao, W and Yuan, G and Klein, ML and Ren, S}, title = {Light-induced dilation in nanosheets of charge-transfer complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3776-3781}, pmid = {29581284}, issn = {1091-6490}, abstract = {We report the observation of a sizable photostrictive effect of 5.7% with fast, submillisecond response times, arising from a light-induced lattice dilation of a molecular nanosheet, composed of the molecular charge-transfer compound dibenzotetrathiafulvalene (DBTTF) and C60 An interfacial self-assembly approach is introduced for the thickness-controlled growth of the thin films. From photoabsorption measurements, molecular simulations, and electronic structure calculations, we suggest that photostriction within these films arises from a transformation in the molecular structure of constituent molecules upon photoinduced charge transfer, as well as the accommodation of free charge carriers within the material. Additionally, we find that the photostrictive properties of the nanosheets are thickness-dependent, a phenomenon that we suggest arises from surface-induced conformational disorder in the molecular components of the film. Moreover, because of the molecular structure in the films, which results largely from interactions between the constituent π-systems and the sulfur atoms of DBTTF, the optoelectronic properties are found to be anisotropic. This work enables the fabrication of 2D molecular charge-transfer nanosheets with tunable thicknesses and properties, suitable for a wide range of applications in flexible electronic technologies.}, } @article {pmid29581283, year = {2018}, author = {McGuire, AD and Lawrence, DM and Koven, C and Clein, JS and Burke, E and Chen, G and Jafarov, E and MacDougall, AH and Marchenko, S and Nicolsky, D and Peng, S and Rinke, A and Ciais, P and Gouttevin, I and Hayes, DJ and Ji, D and Krinner, G and Moore, JC and Romanovsky, V and Schädel, C and Schaefer, K and Schuur, EAG and Zhuang, Q}, title = {Dependence of the evolution of carbon dynamics in the northern permafrost region on the trajectory of climate change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3882-3887}, pmid = {29581283}, issn = {1091-6490}, abstract = {We conducted a model-based assessment of changes in permafrost area and carbon storage for simulations driven by RCP4.5 and RCP8.5 projections between 2010 and 2299 for the northern permafrost region. All models simulating carbon represented soil with depth, a critical structural feature needed to represent the permafrost carbon-climate feedback, but that is not a universal feature of all climate models. Between 2010 and 2299, simulations indicated losses of permafrost between 3 and 5 million km2 for the RCP4.5 climate and between 6 and 16 million km2 for the RCP8.5 climate. For the RCP4.5 projection, cumulative change in soil carbon varied between 66-Pg C (1015-g carbon) loss to 70-Pg C gain. For the RCP8.5 projection, losses in soil carbon varied between 74 and 652 Pg C (mean loss, 341 Pg C). For the RCP4.5 projection, gains in vegetation carbon were largely responsible for the overall projected net gains in ecosystem carbon by 2299 (8- to 244-Pg C gains). In contrast, for the RCP8.5 projection, gains in vegetation carbon were not great enough to compensate for the losses of carbon projected by four of the five models; changes in ecosystem carbon ranged from a 641-Pg C loss to a 167-Pg C gain (mean, 208-Pg C loss). The models indicate that substantial net losses of ecosystem carbon would not occur until after 2100. This assessment suggests that effective mitigation efforts during the remainder of this century could attenuate the negative consequences of the permafrost carbon-climate feedback.}, } @article {pmid29581282, year = {2018}, author = {Viegas, J}, title = {Profile of Dorothy L. Cheney and Robert M. Seyfarth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3735-3738}, pmid = {29581282}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; *Biological Evolution ; Ethology/*history ; History, 20th Century ; History, 21st Century ; Humans ; *Language ; Primates ; *Psychological Theory ; *Social Environment ; }, } @article {pmid29581281, year = {2018}, author = {Russo, J and Akahane, K and Tanaka, H}, title = {Water-like anomalies as a function of tetrahedrality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3333-E3341}, pmid = {29581281}, issn = {1091-6490}, abstract = {Tetrahedral interactions describe the behavior of the most abundant and technologically important materials on Earth, such as water, silicon, carbon, germanium, and countless others. Despite their differences, these materials share unique common physical behaviors, such as liquid anomalies, open crystalline structures, and extremely poor glass-forming ability at ambient pressure. To reveal the physical origin of these anomalies and their link to the shape of the phase diagram, we systematically study the properties of the Stillinger-Weber potential as a function of the strength of the tetrahedral interaction [Formula: see text] We uncover a unique transition to a reentrant spinodal line at low values of [Formula: see text], accompanied with a change in the dynamical behavior, from non-Arrhenius to Arrhenius. We then show that a two-state model can provide a comprehensive understanding on how the thermodynamic and dynamic anomalies of this important class of materials depend on the strength of the tetrahedral interaction. Our work establishes a deep link between the shape of the phase diagram and the thermodynamic and dynamic properties through local structural ordering in liquids and hints at why water is so special among all substances.}, } @article {pmid29581280, year = {2018}, author = {Wang, P and Liang, FC and Wittmann, D and Siegel, A and Shan, SO and Grimm, B}, title = {Chloroplast SRP43 acts as a chaperone for glutamyl-tRNA reductase, the rate-limiting enzyme in tetrapyrrole biosynthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3588-E3596}, pmid = {29581280}, issn = {1091-6490}, support = {R01 GM114390/GM/NIGMS NIH HHS/United States ; }, mesh = {Aldehyde Oxidoreductases/*metabolism ; Arabidopsis/*metabolism ; Arabidopsis Proteins/*metabolism ; Chlorophyll/metabolism ; Chloroplast Proteins/metabolism ; Chloroplasts/*metabolism ; Light-Harvesting Protein Complexes/metabolism ; Molecular Chaperones/metabolism ; Protein Binding ; Protein Folding ; Protein Transport ; Signal Recognition Particle/*metabolism ; Tetrapyrroles/biosynthesis ; }, abstract = {Assembly of light-harvesting complexes requires synchronization of chlorophyll (Chl) biosynthesis with biogenesis of light-harvesting Chl a/b-binding proteins (LHCPs). The chloroplast signal recognition particle (cpSRP) pathway is responsible for transport of nucleus-encoded LHCPs in the stroma of the plastid and their integration into the thylakoid membranes. Correct folding and assembly of LHCPs require the incorporation of Chls, whose biosynthesis must therefore be precisely coordinated with membrane insertion of LHCPs. How the spatiotemporal coordination between the cpSRP machinery and Chl biosynthesis is achieved is poorly understood. In this work, we demonstrate a direct interaction between cpSRP43, the chaperone that mediates LHCP targeting and insertion, and glutamyl-tRNA reductase (GluTR), a rate-limiting enzyme in tetrapyrrole biosynthesis. Concurrent deficiency for cpSRP43 and the GluTR-binding protein (GBP) additively reduces GluTR levels, indicating that cpSRP43 and GBP act nonredundantly to stabilize GluTR. The substrate-binding domain of cpSRP43 binds to the N-terminal region of GluTR, which harbors aggregation-prone motifs, and the chaperone activity of cpSRP43 efficiently prevents aggregation of these regions. Our work thus reveals a function of cpSRP43 in Chl biosynthesis and suggests a striking mechanism for posttranslational coordination of LHCP insertion with Chl biosynthesis.}, } @article {pmid29581279, year = {2018}, author = {Hata, M and Ikeda, HO and Iwai, S and Iida, Y and Gotoh, N and Asaka, I and Ikeda, K and Isobe, Y and Hori, A and Nakagawa, S and Yamato, S and Arita, M and Yoshimura, N and Tsujikawa, A}, title = {Reduction of lipid accumulation rescues Bietti's crystalline dystrophy phenotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3936-3941}, pmid = {29581279}, issn = {1091-6490}, mesh = {Animals ; Cholesterol/analysis/*metabolism ; Corneal Dystrophies, Hereditary/diet therapy/enzymology/genetics/*metabolism ; Cytochrome P450 Family 4/genetics/metabolism ; Humans ; Mice ; Mutation ; Phenotype ; Retinal Diseases/diet therapy/enzymology/genetics/*metabolism ; Retinal Pigment Epithelium/enzymology/metabolism ; }, abstract = {Bietti's crystalline dystrophy (BCD) is an intractable and progressive chorioretinal degenerative disease caused by mutations in the CYP4V2 gene, resulting in blindness in most patients. Although we and others have shown that retinal pigment epithelium (RPE) cells are primarily impaired in patients with BCD, the underlying mechanisms of RPE cell damage are still unclear because we lack access to appropriate disease models and to lesion-affected cells from patients with BCD. Here, we generated human RPE cells from induced pluripotent stem cells (iPSCs) derived from patients with BCD carrying a CYP4V2 mutation and successfully established an in vitro model of BCD, i.e., BCD patient-specific iPSC-RPE cells. In this model, RPE cells showed degenerative changes of vacuolated cytoplasm similar to those in postmortem specimens from patients with BCD. BCD iPSC-RPE cells exhibited lysosomal dysfunction and impairment of autophagy flux, followed by cell death. Lipidomic analyses revealed the accumulation of glucosylceramide and free cholesterol in BCD-affected cells. Notably, we found that reducing free cholesterol by cyclodextrins or δ-tocopherol in RPE cells rescued BCD phenotypes, whereas glucosylceramide reduction did not affect the BCD phenotype. Our data provide evidence that reducing intracellular free cholesterol may have therapeutic efficacy in patients with BCD.}, } @article {pmid29581278, year = {2018}, author = {Sun, H and Xiao, Y and Gao, Y and Zhang, G and Casey, JF and Shen, Y}, title = {Rapid enhancement of chemical weathering recorded by extremely light seawater lithium isotopes at the Permian-Triassic boundary.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3782-3787}, pmid = {29581278}, issn = {1091-6490}, abstract = {Lithium (Li) isotope analyses of sedimentary rocks from the Meishan section in South China reveal extremely light seawater Li isotopic signatures at the Permian-Triassic boundary (PTB), which coincide with the most severe mass extinction in the history of animal life. Using a dynamic seawater lithium box model, we show that the light seawater Li isotopic signatures can be best explained by a significant influx of riverine [Li] with light δ7Li to the ocean realm. The seawater Li isotope excursion started ≥300 Ky before and persisted up to the main extinction event, which is consistent with the eruption time of the Siberian Traps. The eruption of the Siberian Traps exposed an enormous amount of fresh basalt and triggered CO2 release, rapid global warming, and acid rains, which in turn led to a rapid enhancement of continental weathering. The enhanced continental weathering delivered excessive nutrients to the oceans that could lead to marine eutrophication, anoxia, acidification, and ecological perturbation, ultimately resulting in the end-Permian mass extinction.}, } @article {pmid29581277, year = {2018}, author = {Corso, M and Doccula, FG and de Melo, JRF and Costa, A and Verbruggen, N}, title = {Endoplasmic reticulum-localized CCX2 is required for osmotolerance by regulating ER and cytosolic Ca2+ dynamics in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3966-3971}, pmid = {29581277}, issn = {1091-6490}, mesh = {Antiporters/genetics/*metabolism ; Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Calcium/*metabolism ; Cytosol/*metabolism ; Endoplasmic Reticulum/genetics/*metabolism ; Gene Expression Regulation, Plant ; Osmotic Pressure ; Protein Transport ; Signal Transduction ; }, abstract = {Ca2+ signals in plant cells are important for adaptive responses to environmental stresses. Here, we report that the Arabidopsis CATION/Ca2+ EXCHANGER2 (CCX2), encoding a putative cation/Ca2+ exchanger that localizes to the endoplasmic reticulum (ER), is strongly induced by salt and osmotic stresses. Compared with the WT, AtCCX2 loss-of-function mutant was less tolerant to osmotic stress and displayed the most noteworthy phenotypes (less root/shoot growth) during salt stress. Conversely, AtCCX2 gain-of-function mutants were more tolerant to osmotic stress. In addition, AtCCX2 partially suppresses the Ca2+ sensitivity of K667 yeast triple mutant, characterized by Ca2+ uptake deficiency. Remarkably, Cameleon Ca2+ sensors revealed that the absence of AtCCX2 activity results in decreased cytosolic and increased ER Ca2+ concentrations in comparison with both WT and the gain-of-function mutants. This was observed in both salt and nonsalt osmotic stress conditions. It appears that AtCCX2 is directly involved in the control of Ca2+ fluxes between the ER and the cytosol, which plays a key role in the ability of plants to cope with osmotic stresses. To our knowledge, Atccx2 is unique as a plant mutant to show a measured alteration in ER Ca2+ concentrations. In this study, we identified the ER-localized AtCCX2 as a pivotal player in the regulation of ER Ca2+ dynamics that heavily influence plant growth upon salt and osmotic stress.}, } @article {pmid29581276, year = {2018}, author = {Li, W and Adebali, O and Yang, Y and Selby, CP and Sancar, A}, title = {Single-nucleotide resolution dynamic repair maps of UV damage in Saccharomyces cerevisiae genome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3408-E3415}, pmid = {29581276}, issn = {1091-6490}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; R01 ES027255/ES/NIEHS NIH HHS/United States ; R35 GM118102/GM/NIGMS NIH HHS/United States ; }, mesh = {DNA Damage/*radiation effects ; DNA Repair ; DNA, Fungal/genetics/metabolism ; Genome, Fungal/*radiation effects ; Pyrimidine Dimers/genetics/metabolism ; Saccharomyces cerevisiae/*genetics/metabolism/*radiation effects ; Transcription, Genetic ; Ultraviolet Rays ; }, abstract = {We have adapted the eXcision Repair-sequencing (XR-seq) method to generate single-nucleotide resolution dynamic repair maps of UV-induced cyclobutane pyrimidine dimers and (6-4) pyrimidine-pyrimidone photoproducts in the Saccharomyces cerevisiae genome. We find that these photoproducts are removed from the genome primarily by incisions 13-18 nucleotides 5' and 6-7 nucleotides 3' to the UV damage that generate 21- to 27-nt-long excision products. Analyses of the excision repair kinetics both in single genes and at the genome-wide level reveal strong transcription-coupled repair of the transcribed strand at early time points followed by predominantly nontranscribed strand repair at later stages. We have also characterized the excision repair level as a function of the transcription level. The availability of high-resolution and dynamic repair maps should aid in future repair and mutagenesis studies in this model organism.}, } @article {pmid29581275, year = {2018}, author = {Crowe, AM and Workman, SD and Watanabe, N and Worrall, LJ and Strynadka, NCJ and Eltis, LD}, title = {IpdAB, a virulence factor in Mycobacterium tuberculosis, is a cholesterol ring-cleaving hydrolase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3378-E3387}, pmid = {29581275}, issn = {1091-6490}, support = {MOP-1333647//CIHR/Canada ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Acetyl-CoA C-Acetyltransferase/chemistry/genetics/metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Cholesterol/chemistry/*metabolism ; Crystallography, X-Ray ; Humans ; Hydrolases/chemistry/genetics/*metabolism ; Kinetics ; Models, Molecular ; Mycobacterium tuberculosis/chemistry/classification/*enzymology/genetics ; Phylogeny ; Tuberculosis/metabolism/*microbiology ; Virulence Factors/chemistry/genetics/*metabolism ; }, abstract = {Mycobacterium tuberculosis (Mtb) grows on host-derived cholesterol during infection. IpdAB, found in all steroid-degrading bacteria and a determinant of pathogenicity, has been implicated in the hydrolysis of the last steroid ring. Phylogenetic analyses revealed that IpdAB orthologs form a clade of CoA transferases (CoTs). In a coupled assay with a thiolase, IpdAB transformed the cholesterol catabolite (R)-2-(2-carboxyethyl)-3-methyl-6-oxocyclohex-1-ene-1-carboxyl-CoA (COCHEA-CoA) and CoASH to 4-methyl-5-oxo-octanedioyl-CoA (MOODA-CoA) and acetyl-CoA with high specificity (kcat/Km = 5.8 ± 0.8 × 104 M-1⋅s-1). The structure of MOODA-CoA was consistent with IpdAB hydrolyzing COCHEA-CoA to a β-keto-thioester, a thiolase substrate. Contrary to characterized CoTs, IpdAB exhibited no activity toward small CoA thioesters. Further, IpdAB lacks the catalytic glutamate residue that is conserved in the β-subunit of characterized CoTs and a glutamyl-CoA intermediate was not trapped during turnover. By contrast, Glu105A, conserved in the α-subunit of IpdAB, was essential for catalysis. A crystal structure of the IpdAB·COCHEA-CoA complex, solved to 1.4 Å, revealed that Glu105A is positioned to act as a catalytic base. Upon titration with COCHEA-CoA, the E105AA variant accumulated a yellow-colored species (λmax = 310 nm; Kd = 0.4 ± 0.2 μM) typical of β-keto enolates. In the presence of D2O, IpdAB catalyzed the deuteration of COCHEA-CoA adjacent to the hydroxylation site at rates consistent with kcat Based on these data and additional IpdAB variants, we propose a retro-Claisen condensation-like mechanism for the IpdAB-mediated hydrolysis of COCHEA-CoA. This study expands the range of known reactions catalyzed by the CoT superfamily and provides mechanistic insight into an important determinant of Mtb pathogenesis.}, } @article {pmid29581274, year = {2018}, author = {Ke, H and Zhao, L and Zhang, H and Feng, X and Xu, H and Hao, J and Wang, S and Yang, Q and Zou, L and Su, X and Wang, L and Wu, C and Wang, Y and Nie, J and Jiao, B}, title = {Loss of TDP43 inhibits progression of triple-negative breast cancer in coordination with SRSF3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3426-E3435}, pmid = {29581274}, issn = {1091-6490}, mesh = {Alternative Splicing ; Cell Cycle Proteins/genetics/metabolism ; DNA-Binding Proteins/*deficiency/genetics ; Disease Progression ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Membrane Proteins/genetics/metabolism ; Serine-Arginine Splicing Factors/genetics/*metabolism ; Triple Negative Breast Neoplasms/*genetics/metabolism ; }, abstract = {Aberrant alternative splicing has been highlighted as a potential hallmark of cancer. Here, we identify TDP43 (TAR DNA-binding protein 43) as an important splicing regulator responsible for the unique splicing profile in triple-negative breast cancer (TNBC). Clinical data demonstrate that TDP43 is highly expressed in TNBC with poor prognosis. Knockdown of TDP43 inhibits tumor progression, including proliferation and metastasis, and overexpression of TDP43 promotes proliferation and malignancy of mammary epithelial cells. Deep sequencing analysis and functional experiments indicate that TDP43 alters most splicing events with splicing factor SRSF3 (serine/arginine-rich splicing factor 3), in the regulation of TNBC progression. The TDP43/SRSF3 complex controls specific splicing events, including downstream genes PAR3 and NUMB The effect of reduced metastasis and proliferation upon the knockdown of TDP43 or SRSF3 is mediated by the splicing regulation of PAR3 and NUMB exon 12, respectively. The TDP43/SRSF3 complex and downstream PAR3 isoform are potential therapeutic targets for TNBC.}, } @article {pmid29581273, year = {2018}, author = {}, title = {Correction for Paluck et al., Changing climates of conflict: A social network experiment in 56 schools.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3598}, doi = {10.1073/pnas.1804429115}, pmid = {29581273}, issn = {1091-6490}, } @article {pmid29581272, year = {2018}, author = {Harraz, OF and Longden, TA and Dabertrand, F and Hill-Eubanks, D and Nelson, MT}, title = {Endothelial GqPCR activity controls capillary electrical signaling and brain blood flow through PIP2 depletion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3569-E3577}, pmid = {29581272}, issn = {1091-6490}, support = {R01 HL121706/HL/NHLBI NIH HHS/United States ; P01 HL095488/HL/NHLBI NIH HHS/United States ; P30 GM103498/GM/NIGMS NIH HHS/United States ; R37 DK053832/DK/NIDDK NIH HHS/United States ; P20 GM103644/GM/NIGMS NIH HHS/United States ; R01 DK053832/DK/NIDDK NIH HHS/United States ; R01 HL131181/HL/NHLBI NIH HHS/United States ; R01 HL136636/HL/NHLBI NIH HHS/United States ; S10 OD010583/OD/NIH HHS/United States ; }, mesh = {Animals ; Brain/*blood supply/metabolism ; Cerebrovascular Circulation/*physiology ; Endothelial Cells/metabolism ; GTP-Binding Protein alpha Subunits, Gq-G11/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Neurovascular Coupling ; Patch-Clamp Techniques/methods ; Phosphatidylinositol 4,5-Diphosphate/*deficiency/metabolism ; Potassium Channels, Inwardly Rectifying/*metabolism ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; }, abstract = {Brain capillaries play a critical role in sensing neural activity and translating it into dynamic changes in cerebral blood flow to serve the metabolic needs of the brain. The molecular cornerstone of this mechanism is the capillary endothelial cell inward rectifier K+ (Kir2.1) channel, which is activated by neuronal activity-dependent increases in external K+ concentration, producing a propagating hyperpolarizing electrical signal that dilates upstream arterioles. Here, we identify a key regulator of this process, demonstrating that phosphatidylinositol 4,5-bisphosphate (PIP2) is an intrinsic modulator of capillary Kir2.1-mediated signaling. We further show that PIP2 depletion through activation of Gq protein-coupled receptors (GqPCRs) cripples capillary-to-arteriole signal transduction in vitro and in vivo, highlighting the potential regulatory linkage between GqPCR-dependent and electrical neurovascular-coupling mechanisms. These results collectively show that PIP2 sets the gain of capillary-initiated electrical signaling by modulating Kir2.1 channels. Endothelial PIP2 levels would therefore shape the extent of retrograde signaling and modulate cerebral blood flow.}, } @article {pmid29581271, year = {2018}, author = {Dannemann, T and Boyer, D and Miramontes, O}, title = {Lévy flight movements prevent extinctions and maximize population abundances in fragile Lotka-Volterra systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3794-3799}, pmid = {29581271}, issn = {1091-6490}, mesh = {Animals ; Ecosystem ; Feeding Behavior ; *Models, Biological ; *Population Dynamics ; Predatory Behavior ; }, abstract = {Multiple-scale mobility is ubiquitous in nature and has become instrumental for understanding and modeling animal foraging behavior. However, the impact of individual movements on the long-term stability of populations remains largely unexplored. We analyze deterministic and stochastic Lotka-Volterra systems, where mobile predators consume scarce resources (prey) confined in patches. In fragile systems (that is, those unfavorable to species coexistence), the predator species has a maximized abundance and is resilient to degraded prey conditions when individual mobility is multiple scaled. Within the Lévy flight model, highly superdiffusive foragers rarely encounter prey patches and go extinct, whereas normally diffusing foragers tend to proliferate within patches, causing extinctions by overexploitation. Lévy flights of intermediate index allow a sustainable balance between patch exploitation and regeneration over wide ranges of demographic rates. Our analytical and simulated results can explain field observations and suggest that scale-free random movements are an important mechanism by which entire populations adapt to scarcity in fragmented ecosystems.}, } @article {pmid29581270, year = {2018}, author = {Lin, MA and Cannon, SC and Papazian, DM}, title = {Kv4.2 autism and epilepsy mutation enhances inactivation of closed channels but impairs access to inactivated state after opening.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3559-E3568}, pmid = {29581270}, issn = {1091-6490}, support = {R01 GM043459/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Autistic Disorder/*genetics/metabolism ; Epilepsy/*genetics/metabolism ; Female ; Humans ; Kv Channel-Interacting Proteins/genetics/metabolism ; Membrane Potentials/physiology ; Mutation ; Oocytes/physiology ; Patch-Clamp Techniques/methods ; Polymorphism, Genetic ; Repressor Proteins/genetics/metabolism ; Shal Potassium Channels/*genetics/metabolism ; Transfection ; Xenopus laevis ; }, abstract = {A de novo mutation in the KCND2 gene, which encodes the Kv4.2 K+ channel, was identified in twin boys with intractable, infant-onset epilepsy and autism. Kv4.2 channels undergo closed-state inactivation (CSI), a mechanism by which channels inactivate without opening during subthreshold depolarizations. CSI dynamically modulates neuronal excitability and action potential back propagation in response to excitatory synaptic input, controlling Ca2+ influx into dendrites and regulating spike timing-dependent plasticity. Here, we show that the V404M mutation specifically affects the mechanism of CSI, enhancing the inactivation of channels that have not opened while dramatically impairing the inactivation of channels that have opened. The mutation gives rise to these opposing effects by increasing the stability of the inactivated state and in parallel, profoundly slowing the closure of open channels, which according to our data, is required for CSI. The larger volume of methionine compared with valine is a major factor underlying altered inactivation gating. Our results suggest that V404M increases the strength of the physical interaction between the pore gate and the voltage sensor regardless of whether the gate is open or closed. Furthermore, in contrast to previous proposals, our data strongly suggest that physical coupling between the voltage sensor and the pore gate is maintained in the inactivated state. The state-dependent effects of V404M on CSI are expected to disturb the regulation of neuronal excitability and the induction of spike timing-dependent plasticity. Our results strongly support a role for altered CSI gating in the etiology of epilepsy and autism in the affected twins.}, } @article {pmid29581269, year = {2018}, author = {Liao, DA and Zhang, YS and Cai, LX and Ghazanfar, AA}, title = {Internal states and extrinsic factors both determine monkey vocal production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3978-3983}, pmid = {29581269}, issn = {1091-6490}, support = {R01 NS054898/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Arousal ; Callithrix/*physiology ; Female ; Heart Rate ; Male ; Speech ; *Vocalization, Animal ; Voice ; }, abstract = {A key question for understanding speech evolution is whether or not the vocalizations of our closest living relatives-nonhuman primates-represent the precursors to speech. Some believe that primate vocalizations are not volitional but are instead inextricably linked to internal states like arousal and thus bear little resemblance to human speech. Others disagree and believe that since many primates can use their vocalizations strategically, this demonstrates a degree of voluntary vocal control. In the current study, we present a behavioral paradigm that reliably elicits different types of affiliative vocalizations from marmoset monkeys while measuring their heart rate fluctuations using noninvasive electromyography. By modulating both the physical distance between marmosets and the sensory information available to them, we find that arousal levels are linked, but not inextricably, to vocal production. Different arousal levels are, generally, associated with changes in vocal acoustics and the drive to produce different call types. However, in contexts where marmosets are interacting, the production of these different call types is also affected by extrinsic factors such as the timing of a conspecific's vocalization. These findings suggest that variability in vocal output as a function of context might reflect trade-offs between the drive to perpetuate vocal contact and conserving energy.}, } @article {pmid29581268, year = {2018}, author = {Nan, J and Wang, Y and Yang, J and Stark, GR}, title = {IRF9 and unphosphorylated STAT2 cooperate with NF-κB to drive IL6 expression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3906-3911}, pmid = {29581268}, issn = {1091-6490}, support = {P01 CA062220/CA/NCI NIH HHS/United States ; }, mesh = {Gene Expression Regulation ; Humans ; Interferon-Stimulated Gene Factor 3, gamma Subunit/*metabolism ; Interferon-beta/genetics/metabolism ; Interleukin-6/*genetics/metabolism ; NF-kappa B/genetics/*metabolism ; Phosphorylation ; Promoter Regions, Genetic ; Response Elements ; STAT2 Transcription Factor/genetics/*metabolism ; STAT3 Transcription Factor/genetics/metabolism ; Signal Transduction ; Up-Regulation ; }, abstract = {In response to IFNβ, the IL6 gene is activated, modestly at early times by ISGF3 (IRF9 plus tyrosine-phosphorylated STATs 1 and 2), and strongly at late times by U-ISGF3 (IRF9 plus U-STATs 1 and 2, lacking tyrosine phosphorylation). A classical IFN-stimulated response element (ISRE) at -1,513 to -1,526 in the human IL6 promoter is required. Pretreating cells with IFNβ or increasing the expression of U-STAT2 and IRF9 exogenously greatly enhances IL6 expression in response to the classical NF-κB activators IL1, TNF, and LPS. U-STAT2 binds tightly to IRF9, the DNA binding subunit of ISGF3, and also to the p65 subunit of NF-κB. Therefore, as shown by ChIP analyses, U-STAT2 can bridge the ISRE and κB elements in the IL6 promoter. In some cancer cells, the protumorigenic activation of STAT3 will be enhanced by the increased synthesis of IL6 that is facilitated by high expression of U-STAT2 and IRF9.}, } @article {pmid29581267, year = {2018}, author = {Beglov, D and Hall, DR and Wakefield, AE and Luo, L and Allen, KN and Kozakov, D and Whitty, A and Vajda, S}, title = {Exploring the structural origins of cryptic sites on proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3416-E3425}, pmid = {29581267}, issn = {1091-6490}, support = {R35 GM118078/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Ligands ; Molecular Dynamics Simulation ; Protein Binding ; Protein Conformation ; Proteins/*chemistry ; }, abstract = {Molecular dynamics (MD) simulations of proteins reveal the existence of many transient surface pockets; however, the factors determining what small subset of these represent druggable or functionally relevant ligand binding sites, called "cryptic sites," are not understood. Here, we examine multiple X-ray structures for a set of proteins with validated cryptic sites, using the computational hot spot identification tool FTMap. The results show that cryptic sites in ligand-free structures generally have a strong binding energy hot spot very close by. As expected, regions around cryptic sites exhibit above-average flexibility, and close to 50% of the proteins studied here have unbound structures that could accommodate the ligand without clashes. Nevertheless, the strong hot spot neighboring each cryptic site is almost always exploited by the bound ligand, suggesting that binding may frequently involve an induced fit component. We additionally evaluated the structural basis for cryptic site formation, by comparing unbound to bound structures. Cryptic sites are most frequently occluded in the unbound structure by intrusion of loops (22.5%), side chains (19.4%), or in some cases entire helices (5.4%), but motions that create sites that are too open can also eliminate pockets (19.4%). The flexibility of cryptic sites frequently leads to missing side chains or loops (12%) that are particularly evident in low resolution crystal structures. An interesting observation is that cryptic sites formed solely by the movement of side chains, or of backbone segments with fewer than five residues, result only in low affinity binding sites with limited use for drug discovery.}, } @article {pmid29581266, year = {2018}, author = {Ponsot, E and Burred, JJ and Belin, P and Aucouturier, JJ}, title = {Cracking the social code of speech prosody using reverse correlation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3972-3977}, pmid = {29581266}, issn = {1091-6490}, support = {335536//European Research Council/International ; }, mesh = {Adult ; Auditory Perception ; Emotions ; Female ; Humans ; Judgment ; Male ; Middle Aged ; Random Allocation ; *Social Behavior ; *Speech ; Speech Perception ; Trust ; *Voice ; Young Adult ; }, abstract = {Human listeners excel at forming high-level social representations about each other, even from the briefest of utterances. In particular, pitch is widely recognized as the auditory dimension that conveys most of the information about a speaker's traits, emotional states, and attitudes. While past research has primarily looked at the influence of mean pitch, almost nothing is known about how intonation patterns, i.e., finely tuned pitch trajectories around the mean, may determine social judgments in speech. Here, we introduce an experimental paradigm that combines state-of-the-art voice transformation algorithms with psychophysical reverse correlation and show that two of the most important dimensions of social judgments, a speaker's perceived dominance and trustworthiness, are driven by robust and distinguishing pitch trajectories in short utterances like the word "Hello," which remained remarkably stable whether male or female listeners judged male or female speakers. These findings reveal a unique communicative adaptation that enables listeners to infer social traits regardless of speakers' physical characteristics, such as sex and mean pitch. By characterizing how any given individual's mental representations may differ from this generic code, the method introduced here opens avenues to explore dysprosody and social-cognitive deficits in disorders like autism spectrum and schizophrenia. In addition, once derived experimentally, these prototypes can be applied to novel utterances, thus providing a principled way to modulate personality impressions in arbitrary speech signals.}, } @article {pmid29581265, year = {2018}, author = {Lin, C and Top, D and Manahan, CC and Young, MW and Crane, BR}, title = {Circadian clock activity of cryptochrome relies on tryptophan-mediated photoreduction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3822-3827}, pmid = {29581265}, issn = {1091-6490}, support = {R01 GM054339/GM/NIGMS NIH HHS/United States ; R35 GM122535/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Amino Acid Substitution ; Animals ; *Circadian Clocks ; Cryptochromes/*chemistry/genetics/*metabolism ; Dinitrocresols/metabolism ; Drosophila/chemistry/genetics/*metabolism/radiation effects ; Drosophila Proteins/*chemistry/genetics/*metabolism ; Eye Proteins/*chemistry/genetics/*metabolism ; Light ; Oxidation-Reduction/radiation effects ; Tryptophan/*chemistry/metabolism ; }, abstract = {Cryptochromes (CRYs) entrain the circadian clocks of plants and animals to light. Irradiation of the Drosophila cryptochrome (dCRY) causes reduction of an oxidized flavin cofactor by a chain of conserved tryptophan (Trp) residues. However, it is unclear how redox chemistry within the Trp chain couples to dCRY-mediated signaling. Here, we show that substitutions of four key Trp residues to redox-active tyrosine and redox-inactive phenylalanine tune the light sensitivity of dCRY photoreduction, conformational activation, cellular stability, and targeted degradation of the clock protein timeless (TIM). An essential surface Trp gates electron flow into the flavin cofactor, but can be relocated for enhanced photoactivation. Differential effects of Trp-mediated flavin photoreduction on cellular turnover of TIM and dCRY indicate that these activities are separated in time and space. Overall, the dCRY Trp chain has evolutionary importance for light sensing, and its manipulation has implications for optogenetic applications of CRYs.}, } @article {pmid29581264, year = {2018}, author = {}, title = {Correction for Bernardo-Seisdedos et al., Structural basis and energy landscape for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3599}, doi = {10.1073/pnas.1804137115}, pmid = {29581264}, issn = {1091-6490}, } @article {pmid29581263, year = {2018}, author = {Chen, PY and Aman, H and Can, M and Ragsdale, SW and Drennan, CL}, title = {Binding site for coenzyme A revealed in the structure of pyruvate:ferredoxin oxidoreductase from Moorella thermoacetica.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3846-3851}, pmid = {29581263}, issn = {1091-6490}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 GM039451/GM/NIGMS NIH HHS/United States ; R01 GM069857/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R37 GM039451/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/genetics/metabolism ; Binding Sites ; Carbon Dioxide/chemistry/metabolism ; Coenzyme A/chemistry/*metabolism ; Crystallography, X-Ray ; Ferredoxins/chemistry/metabolism ; Kinetics ; Moorella/chemistry/*enzymology/genetics ; Pyruvate Synthase/*chemistry/genetics/*metabolism ; Pyruvic Acid/chemistry/metabolism ; }, abstract = {Pyruvate:ferredoxin oxidoreductase (PFOR) is a microbial enzyme that uses thiamine pyrophosphate (TPP), three [4Fe-4S] clusters, and coenzyme A (CoA) in the reversible oxidation of pyruvate to generate acetyl-CoA and carbon dioxide. The two electrons that are generated as a result of pyruvate decarboxylation are used in the reduction of low potential ferredoxins, which provide reducing equivalents for central metabolism, including the Wood-Ljungdahl pathway. PFOR is a member of the 2-oxoacid:ferredoxin oxidoreductase (OFOR) superfamily, which plays major roles in both microbial redox reactions and carbon dioxide fixation. Here, we present a set of crystallographic snapshots of the best-studied member of this superfamily, the PFOR from Moorella thermoacetica (MtPFOR). These snapshots include the native structure, those of lactyl-TPP and acetyl-TPP reaction intermediates, and the first of an OFOR with CoA bound. These structural data reveal the binding site of CoA as domain III, the function of which in OFORs was previously unknown, and establish sequence motifs for CoA binding in the OFOR superfamily. MtPFOR structures further show that domain III undergoes a conformational change upon CoA binding that seals off the active site and positions the thiolate of CoA directly adjacent to the TPP cofactor. These structural findings provide a molecular basis for the experimental observation that CoA binding accelerates catalysis by 105-fold.}, } @article {pmid29581262, year = {2018}, author = {Yang, C and Zhang, L and Liu, B and Xu, S and Hamann, T and McOwen, D and Dai, J and Luo, W and Gong, Y and Wachsman, ED and Hu, L}, title = {Continuous plating/stripping behavior of solid-state lithium metal anode in a 3D ion-conductive framework.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3770-3775}, pmid = {29581262}, issn = {1091-6490}, abstract = {The increasing demands for efficient and clean energy-storage systems have spurred the development of Li metal batteries, which possess attractively high energy densities. For practical application of Li metal batteries, it is vital to resolve the intrinsic problems of Li metal anodes, i.e., the formation of Li dendrites, interfacial instability, and huge volume changes during cycling. Utilization of solid-state electrolytes for Li metal anodes is a promising approach to address those issues. In this study, we use a 3D garnet-type ion-conductive framework as a host for the Li metal anode and study the plating and stripping behaviors of the Li metal anode within the solid ion-conductive host. We show that with a solid-state ion-conductive framework and a planar current collector at the bottom, Li is plated from the bottom and rises during deposition, away from the separator layer and free from electrolyte penetration and short circuit. Owing to the solid-state deposition property, Li grows smoothly in the pores of the garnet host without forming Li dendrites. The dendrite-free deposition and continuous rise/fall of Li metal during plating/stripping in the 3D ion-conductive host promise a safe and durable Li metal anode. The solid-state Li anode shows stable cycling at 0.5 mA cm-2 for 300 h with a small overpotential, showing a significant improvement compared with reported Li anodes with ceramic electrolytes. By fundamentally eliminating the dendrite issue, the solid Li metal anode shows a great potential to build safe and reliable Li metal batteries.}, } @article {pmid29581261, year = {2018}, author = {Song, L and Zhang, Y and Chen, W and Gu, T and Zhang, SY and Ji, Q}, title = {Mechanistic insights into staphylopine-mediated metal acquisition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3942-3947}, pmid = {29581261}, issn = {1091-6490}, mesh = {Bacterial Proteins/chemistry/genetics/*metabolism ; Carrier Proteins/chemistry/genetics/*metabolism ; Cobalt/chemistry/*metabolism ; Humans ; Imidazoles/*metabolism ; Nickel/chemistry/*metabolism ; Protein Binding ; Protein Domains ; Staphylococcal Infections/metabolism/*microbiology ; Staphylococcus aureus/chemistry/genetics/*metabolism ; Zinc/chemistry/*metabolism ; }, abstract = {Metal acquisition is vital to pathogens for successful infection within hosts. Staphylopine (StP), a broad-spectrum metallophore biosynthesized by the major human pathogen, Staphylococcus aureus, plays a central role in transition-metal acquisition and bacterial virulence. The StP-like biosynthesis loci are present in various pathogens, and the proteins responsible for StP/metal transportation have been determined. However, the molecular mechanisms of how StP/metal complexes are recognized and transported remain unknown. We report multiple structures of the extracytoplasmic solute-binding protein CntA from the StP/metal transportation system in apo form and in complex with StP and three different metals. We elucidated a sophisticated metal-bound StP recognition mechanism and determined that StP/metal binding triggers a notable interdomain conformational change in CntA. Furthermore, CRISPR/Cas9-mediated single-base substitution mutations and biochemical analysis highlight the importance of StP/metal recognition for StP/metal acquisition. These discoveries provide critical insights into the study of novel metal-acquisition mechanisms in microbes.}, } @article {pmid29581260, year = {2018}, author = {Gruber, A and Hornburg, D and Antonin, M and Krahmer, N and Collado, J and Schaffer, M and Zubaite, G and Lüchtenborg, C and Sachsenheimer, T and Brügger, B and Mann, M and Baumeister, W and Hartl, FU and Hipp, MS and Fernández-Busnadiego, R}, title = {Molecular and structural architecture of polyQ aggregates in yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3446-E3453}, pmid = {29581260}, issn = {1091-6490}, support = {318987//European Research Council/International ; }, mesh = {Humans ; Huntington Disease/genetics/metabolism ; Inclusion Bodies/chemistry/genetics/metabolism ; Lipid Droplets/chemistry/metabolism ; Mitochondria/chemistry/metabolism ; Peptides/chemistry/*metabolism/toxicity ; Proteomics ; Saccharomyces cerevisiae/chemistry/drug effects/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; }, abstract = {Huntington's disease is caused by the expansion of a polyglutamine (polyQ) tract in the N-terminal exon of huntingtin (HttEx1), but the cellular mechanisms leading to neurodegeneration remain poorly understood. Here we present in situ structural studies by cryo-electron tomography of an established yeast model system of polyQ toxicity. We find that expression of polyQ-expanded HttEx1 results in the formation of unstructured inclusion bodies and in some cases fibrillar aggregates. This contrasts with recent findings in mammalian cells, where polyQ inclusions were exclusively fibrillar. In yeast, polyQ toxicity correlates with alterations in mitochondrial and lipid droplet morphology, which do not arise from physical interactions with inclusions or fibrils. Quantitative proteomic analysis shows that polyQ aggregates sequester numerous cellular proteins and cause a major change in proteome composition, most significantly in proteins related to energy metabolism. Thus, our data point to a multifaceted toxic gain-of-function of polyQ aggregates, driven by sequestration of endogenous proteins and mitochondrial and lipid droplet dysfunction.}, } @article {pmid29581259, year = {2018}, author = {Sheng, N and Bemben, MA and Díaz-Alonso, J and Tao, W and Shi, YS and Nicoll, RA}, title = {LTP requires postsynaptic PDZ-domain interactions with glutamate receptor/auxiliary protein complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3948-3953}, pmid = {29581259}, issn = {1091-6490}, support = {R01 MH070957/MH/NIMH NIH HHS/United States ; R01 MH080379/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Calcium Channels/chemistry/genetics/*metabolism ; Humans ; *Long-Term Potentiation ; PDZ Domains ; Protein Binding ; Receptors, AMPA/chemistry/genetics/*metabolism ; Receptors, Kainic Acid/genetics/metabolism ; Synapses/chemistry/genetics/*metabolism ; }, abstract = {Long-term potentiation (LTP) is a persistent strengthening of synaptic transmission in the brain and is arguably the most compelling cellular and molecular model for learning and memory. Previous work found that both AMPA receptors and exogenously expressed kainate receptors are equally capable of expressing LTP, despite their limited homology and their association with distinct auxiliary subunits, indicating that LTP is far more promiscuous than previously thought. What might these two subtypes of glutamate receptor have in common? Using a single-cell molecular replacement strategy, we demonstrate that the AMPA receptor auxiliary subunit TARP γ-8, via its PDZ-binding motif, is indispensable for both basal synaptic transmission and LTP. Remarkably, kainate receptors and their auxiliary subunits Neto proteins share the same requirement of PDZ-binding domains for synaptic trafficking and LTP. Together, these results suggest that a minimal postsynaptic requirement for LTP is the PDZ binding of glutamate receptors/auxiliary subunits to PSD scaffolding proteins.}, } @article {pmid29581258, year = {2018}, author = {Zhu, X and Li, S and Pan, S and Xin, X and Gu, Y}, title = {CSI1, PATROL1, and exocyst complex cooperate in delivery of cellulose synthase complexes to the plasma membrane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3578-E3587}, pmid = {29581258}, issn = {1091-6490}, mesh = {Arabidopsis/*metabolism ; Arabidopsis Proteins/*metabolism ; Carrier Proteins/*metabolism ; Cell Membrane/metabolism ; Cellulose/biosynthesis/metabolism ; Cytoplasm/metabolism ; Glucosyltransferases/*metabolism ; Microtubules/metabolism ; Protein Transport ; Vesicular Transport Proteins ; }, abstract = {Cellulose synthesis occurs exclusively at the plasma membrane by cellulose synthase complexes (CSCs). Therefore, delivery of CSCs to discrete sites at the plasma membrane is critical for cellulose synthesis. Despite their significance, the delivery of CSCs is poorly understood. Here we used proteomics approaches, functional genetics, and live cell imaging to show that the de novo secretion of CSCs is mediated by cooperation among cellulose synthase interactive 1 (CSI1), the plant-specific protein PATROL1, and exocyst complex in Arabidopsis thaliana We propose that CSI1 plays a role in marking the docking site, which allows CSCs-containing vesicles access to the plasma membrane through its interaction with microtubules. PATROL1 assists in exocytosis by its interaction with multiple components, including CSI1, CSCs, and exocyst subunits. Both PATROL1 and the exocyst complex determine the rate of delivery of CSCs to the plasma membrane. By monitoring the exocyst complex, PATROL1, CSI1, and CSCs dynamics in real time, we present a timeline of events for exocytosis of CSCs. Our findings provide unique insights into the evolution of exocytosis in eukaryotes.}, } @article {pmid29581257, year = {2018}, author = {Gibson, GM and Toninelli, E and Horsley, SAR and Spalding, GC and Hendry, E and Phillips, DB and Padgett, MJ}, title = {Reversal of orbital angular momentum arising from an extreme Doppler shift.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3800-3803}, pmid = {29581257}, issn = {1091-6490}, abstract = {The linear Doppler shift is familiar as the rise and fall in pitch of a siren as it passes by. Less well known is the rotational Doppler shift, proportional to the rotation rate between source and receiver, multiplied by the angular momentum carried by the beam. In extreme cases the Doppler shift can be larger than the rest-frame frequency and for a red shift, the observed frequency then becomes "negative." In the linear case, this effect is associated with the time reversal of the received signal, but it can be observed only with supersonic relative motion between the source and receiver. However, the rotational case is different; if the radius of rotation is smaller than the wavelength, then the velocities required to observe negative frequencies are subsonic. Using an acoustic source at [Formula: see text]100 Hz we create a rotational Doppler shift larger than the laboratory-frame frequency. We observe that once the red-shifted wave passes into the "negative frequency" regime, the angular momentum associated with the sound is reversed in sign compared with that of the laboratory frame. These low-velocity laboratory realizations of extreme Doppler shifts have relevance to superoscillatory fields and offer unique opportunities to probe interactions with rotating bodies and aspects of pseudorelativistic frame translation.}, } @article {pmid29581256, year = {2018}, author = {Chen, D and Tong, J and Yang, L and Wei, L and Stolz, DB and Yu, J and Zhang, J and Zhang, L}, title = {PUMA amplifies necroptosis signaling by activating cytosolic DNA sensors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3930-3935}, pmid = {29581256}, issn = {1091-6490}, support = {R01 CA215481/CA/NCI NIH HHS/United States ; R01 CA203028/CA/NCI NIH HHS/United States ; U19 AI068021/AI/NIAID NIH HHS/United States ; P30 CA047904/CA/NCI NIH HHS/United States ; R01 CA172136/CA/NCI NIH HHS/United States ; U01 DK085570/DK/NIDDK NIH HHS/United States ; R01 CA217141/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; *Apoptosis ; Apoptosis Regulatory Proteins/genetics/*metabolism ; Cell Line, Tumor ; Cytosol/metabolism ; DNA/genetics/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Glycoproteins/genetics/*metabolism ; Humans ; Membrane Proteins/genetics/*metabolism ; Mice ; Mitochondria/genetics/metabolism ; NF-kappa B/genetics/metabolism ; Necrosis/genetics/*metabolism/physiopathology ; Phosphorylation ; Protein Kinases/genetics/metabolism ; Proto-Oncogene Proteins/genetics/*metabolism ; Receptor-Interacting Protein Serine-Threonine Kinases/genetics/metabolism ; Signal Transduction ; Tumor Necrosis Factor-alpha/genetics/metabolism ; Tumor Suppressor Proteins/genetics/*metabolism ; }, abstract = {Necroptosis, a form of regulated necrotic cell death, is governed by RIP1/RIP3-mediated activation of MLKL. However, the signaling process leading to necroptotic death remains to be elucidated. In this study, we found that PUMA, a proapoptotic BH3-only Bcl-2 family member, is transcriptionally activated in an RIP3/MLKL-dependent manner following induction of necroptosis. The induction of PUMA, which is mediated by autocrine TNF-α and enhanced NF-κB activity, contributes to necroptotic death in RIP3-expressing cells with caspases inhibited. On induction, PUMA promotes the cytosolic release of mitochondrial DNA and activation of the DNA sensors DAI/Zbp1 and STING, leading to enhanced RIP3 and MLKL phosphorylation in a positive feedback loop. Furthermore, deletion of PUMA partially rescues necroptosis-mediated developmental defects in FADD-deficient embryos. Collectively, our results reveal a signal amplification mechanism mediated by PUMA and cytosolic DNA sensors that is involved in TNF-driven necroptotic death in vitro and in vivo.}, } @article {pmid29581255, year = {2018}, author = {Ingram, JR and Blomberg, OS and Rashidian, M and Ali, L and Garforth, S and Fedorov, E and Fedorov, AA and Bonanno, JB and Le Gall, C and Crowley, S and Espinosa, C and Biary, T and Keliher, EJ and Weissleder, R and Almo, SC and Dougan, SK and Ploegh, HL and Dougan, M}, title = {Anti-CTLA-4 therapy requires an Fc domain for efficacy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3912-3917}, pmid = {29581255}, issn = {1091-6490}, support = {DP1 GM106409/GM/NIGMS NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 HG008325/HG/NHGRI NIH HHS/United States ; F32 CA210568/CA/NCI NIH HHS/United States ; K08 DK114563/DK/NIDDK NIH HHS/United States ; U54 GM094662/GM/NIGMS NIH HHS/United States ; U01 GM094665/GM/NIGMS NIH HHS/United States ; R01 GM100518/GM/NIGMS NIH HHS/United States ; P30 CA013330/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/administration & dosage/chemistry/immunology ; CTLA-4 Antigen/chemistry/*immunology ; Cell Line, Tumor ; Disease Models, Animal ; Humans ; Immunoglobulin Fc Fragments/*administration & dosage/chemistry/immunology ; Immunoglobulin Fragments/*administration & dosage/chemistry/immunology ; Immunoglobulin G/administration & dosage/immunology ; Immunotherapy ; Mice ; Mice, Inbred C57BL ; Neoplasms/immunology/*therapy ; Protein Domains ; }, abstract = {Ipilimumab, a monoclonal antibody that recognizes cytotoxic T lymphocyte antigen (CTLA)-4, was the first approved "checkpoint"-blocking anticancer therapy. In mouse tumor models, the response to antibodies against CTLA-4 depends entirely on expression of the Fcγ receptor (FcγR), which may facilitate antibody-dependent cellular phagocytosis, but the contribution of simple CTLA-4 blockade remains unknown. To understand the role of CTLA-4 blockade in the complete absence of Fc-dependent functions, we developed H11, a high-affinity alpaca heavy chain-only antibody fragment (VHH) against CTLA-4. The VHH H11 lacks an Fc portion, binds monovalently to CTLA-4, and inhibits interactions between CTLA-4 and its ligand by occluding the ligand-binding motif on CTLA-4 as shown crystallographically. We used H11 to visualize CTLA-4 expression in vivo using whole-animal immuno-PET, finding that surface-accessible CTLA-4 is largely confined to the tumor microenvironment. Despite this, H11-mediated CTLA-4 blockade has minimal effects on antitumor responses. Installation of the murine IgG2a constant region on H11 dramatically enhances its antitumor response. Coadministration of the monovalent H11 VHH blocks the efficacy of a full-sized therapeutic antibody. We were thus able to demonstrate that CTLA-4-binding antibodies require an Fc domain for antitumor effect.}, } @article {pmid29581254, year = {2018}, author = {Flack, CE and Parkinson, JS}, title = {A zipped-helix cap potentiates HAMP domain control of chemoreceptor signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3519-E3528}, pmid = {29581254}, issn = {1091-6490}, support = {F32 GM119355/GM/NIGMS NIH HHS/United States ; P30 CA042014/CA/NCI NIH HHS/United States ; R01 GM019559/GM/NIGMS NIH HHS/United States ; R37 GM019559/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenylyl Cyclases/genetics/metabolism ; Amino Acid Motifs ; Bacterial Proteins/metabolism ; Chemoreceptor Cells/*metabolism/*physiology ; Chemotaxis/*physiology ; Escherichia coli/enzymology/*genetics/*metabolism ; Escherichia coli Proteins/metabolism ; Histidine Kinase/genetics/metabolism ; Membrane Proteins/metabolism ; Methyl-Accepting Chemotaxis Proteins/genetics/metabolism ; Models, Molecular ; Phosphoric Monoester Hydrolases/genetics/metabolism ; Protein Domains ; Serine/metabolism ; Signal Transduction ; }, abstract = {Environmental awareness is an essential attribute for all organisms. The chemotaxis system of Escherichia coli provides a powerful experimental model for the investigation of stimulus detection and signaling mechanisms at the molecular level. These bacteria sense chemical gradients with transmembrane proteins [methyl-accepting chemotaxis proteins (MCPs)] that have an extracellular ligand-binding domain and intracellular histidine kinases, adenylate cyclases, methyl-accepting proteins, and phosphatases (HAMP) and signaling domains that govern locomotor behavior. HAMP domains are versatile input-output elements that operate in a variety of bacterial signaling proteins, including the sensor kinases of two-component regulatory systems. The MCP HAMP domain receives stimulus information and in turn modulates output signaling activity. This study describes mutants of the Escherichia coli serine chemoreceptor, Tsr, that identify a heptad-repeat structural motif (LLF) at the membrane-proximal end of the receptor signaling domain that is critical for HAMP output control. The homodimeric Tsr signaling domain is an extended, antiparallel, four-helix bundle that controls the activity of an associated kinase. The N terminus of each subunit adjoins the HAMP domain; the LLF residues lie at the C terminus of the methylation-helix bundle. We found, by using in vivo Förster resonance energy transfer kinase assays, that most amino acid replacements at any of the LLF residues abrogate chemotactic responses to serine and lock Tsr output in a kinase-active state, impervious to HAMP-mediated down-regulation. We present evidence that the LLF residues may function like a leucine zipper to promote stable association of the C-terminal signaling helices, thereby creating a metastable helix-packing platform for the N-terminal signaling helices that facilitates conformational control by the HAMP domains in MCP-family chemoreceptors.}, } @article {pmid29581253, year = {2018}, author = {Drazic, A and Aksnes, H and Marie, M and Boczkowska, M and Varland, S and Timmerman, E and Foyn, H and Glomnes, N and Rebowski, G and Impens, F and Gevaert, K and Dominguez, R and Arnesen, T}, title = {NAA80 is actin's N-terminal acetyltransferase and regulates cytoskeleton assembly and cell motility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4399-4404}, pmid = {29581253}, issn = {1091-6490}, support = {R01 GM073791/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetylation ; Acetyltransferases/genetics/*metabolism ; Actin Cytoskeleton/*enzymology/genetics ; Actin-Related Protein 2-3 Complex/genetics/*metabolism ; Cell Movement/*physiology ; HEK293 Cells ; Humans ; N-Terminal Acetyltransferases/genetics/*metabolism ; Pseudopodia/*enzymology/genetics ; }, abstract = {Actin, one of the most abundant proteins in nature, participates in countless cellular functions ranging from organelle trafficking and pathogen motility to cell migration and regulation of gene transcription. Actin's cellular activities depend on the dynamic transition between its monomeric and filamentous forms, a process exquisitely regulated in cells by a large number of actin-binding and signaling proteins. Additionally, several posttranslational modifications control the cellular functions of actin, including most notably N-terminal (Nt)-acetylation, a prevalent modification throughout the animal kingdom. However, the biological role and mechanism of actin Nt-acetylation are poorly understood, and the identity of actin's N-terminal acetyltransferase (NAT) has remained a mystery. Here, we reveal that NAA80, a suggested NAT enzyme whose substrate specificity had not been characterized, is Nt-acetylating actin. We further show that actin Nt-acetylation plays crucial roles in cytoskeletal assembly in vitro and in cells. The absence of Nt-acetylation leads to significant differences in the rates of actin filament depolymerization and elongation, including elongation driven by formins, whereas filament nucleation by the Arp2/3 complex is mostly unaffected. NAA80-knockout cells display severely altered cytoskeletal organization, including an increase in the ratio of filamentous to globular actin, increased filopodia and lamellipodia formation, and accelerated cell motility. Together, the results demonstrate NAA80's role as actin's NAT and reveal a crucial role for actin Nt-acetylation in the control of cytoskeleton structure and dynamics.}, } @article {pmid29581252, year = {2018}, author = {Klein, EY and Van Boeckel, TP and Martinez, EM and Pant, S and Gandra, S and Levin, SA and Goossens, H and Laxminarayan, R}, title = {Global increase and geographic convergence in antibiotic consumption between 2000 and 2015.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3463-E3470}, pmid = {29581252}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/supply & distribution/*therapeutic use ; Bacterial Infections/drug therapy ; Drug Resistance, Microbial/drug effects ; Economics ; Health Services Accessibility ; Humans ; }, abstract = {Tracking antibiotic consumption patterns over time and across countries could inform policies to optimize antibiotic prescribing and minimize antibiotic resistance, such as setting and enforcing per capita consumption targets or aiding investments in alternatives to antibiotics. In this study, we analyzed the trends and drivers of antibiotic consumption from 2000 to 2015 in 76 countries and projected total global antibiotic consumption through 2030. Between 2000 and 2015, antibiotic consumption, expressed in defined daily doses (DDD), increased 65% (21.1-34.8 billion DDDs), and the antibiotic consumption rate increased 39% (11.3-15.7 DDDs per 1,000 inhabitants per day). The increase was driven by low- and middle-income countries (LMICs), where rising consumption was correlated with gross domestic product per capita (GDPPC) growth (P = 0.004). In high-income countries (HICs), although overall consumption increased modestly, DDDs per 1,000 inhabitants per day fell 4%, and there was no correlation with GDPPC. Of particular concern was the rapid increase in the use of last-resort compounds, both in HICs and LMICs, such as glycylcyclines, oxazolidinones, carbapenems, and polymyxins. Projections of global antibiotic consumption in 2030, assuming no policy changes, were up to 200% higher than the 42 billion DDDs estimated in 2015. Although antibiotic consumption rates in most LMICs remain lower than in HICs despite higher bacterial disease burden, consumption in LMICs is rapidly converging to rates similar to HICs. Reducing global consumption is critical for reducing the threat of antibiotic resistance, but reduction efforts must balance access limitations in LMICs and take account of local and global resistance patterns.}, } @article {pmid29581251, year = {2018}, author = {Shepon, A and Eshel, G and Noor, E and Milo, R}, title = {The opportunity cost of animal based diets exceeds all food losses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3804-3809}, pmid = {29581251}, issn = {1091-6490}, abstract = {Food loss is widely recognized as undermining food security and environmental sustainability. However, consumption of resource-intensive food items instead of more efficient, equally nutritious alternatives can also be considered as an effective food loss. Here we define and quantify these opportunity food losses as the food loss associated with consuming resource-intensive animal-based items instead of plant-based alternatives which are nutritionally comparable, e.g., in terms of protein content. We consider replacements that minimize cropland use for each of the main US animal-based food categories. We find that although the characteristic conventional retail-to-consumer food losses are ≈30% for plant and animal products, the opportunity food losses of beef, pork, dairy, poultry, and eggs are 96%, 90%, 75%, 50%, and 40%, respectively. This arises because plant-based replacement diets can produce 20-fold and twofold more nutritionally similar food per cropland than beef and eggs, the most and least resource-intensive animal categories, respectively. Although conventional and opportunity food losses are both targets for improvement, the high opportunity food losses highlight the large potential savings beyond conventionally defined food losses. Concurrently replacing all animal-based items in the US diet with plant-based alternatives will add enough food to feed, in full, 350 million additional people, well above the expected benefits of eliminating all supply chain food waste. These results highlight the importance of dietary shifts to improving food availability and security.}, } @article {pmid29581250, year = {2018}, author = {Sehrawat, A and Gao, L and Wang, Y and Bankhead, A and McWeeney, SK and King, CJ and Schwartzman, J and Urrutia, J and Bisson, WH and Coleman, DJ and Joshi, SK and Kim, DH and Sampson, DA and Weinmann, S and Kallakury, BVS and Berry, DL and Haque, R and Van Den Eeden, SK and Sharma, S and Bearss, J and Beer, TM and Thomas, GV and Heiser, LM and Alumkal, JJ}, title = {LSD1 activates a lethal prostate cancer gene network independently of its demethylase function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {18}, pages = {E4179-E4188}, pmid = {29581250}, issn = {1091-6490}, support = {R01 CA100743/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; P50 CA097186/CA/NCI NIH HHS/United States ; P30 CA051008/CA/NCI NIH HHS/United States ; R01 CA178610/CA/NCI NIH HHS/United States ; R01 CA169172/CA/NCI NIH HHS/United States ; P30 CA069533/CA/NCI NIH HHS/United States ; }, mesh = {Cell Survival/drug effects/genetics ; *Gene Regulatory Networks ; Histone Demethylases/antagonists & inhibitors/genetics/*metabolism ; Humans ; Hydrazines/pharmacology ; Male ; Neoplasm Proteins/antagonists & inhibitors/genetics/*metabolism ; Prostatic Neoplasms, Castration-Resistant/drug therapy/*enzymology/genetics/pathology ; Sulfonamides/pharmacology ; Trans-Activators/genetics/metabolism ; }, abstract = {Medical castration that interferes with androgen receptor (AR) function is the principal treatment for advanced prostate cancer. However, clinical progression is universal, and tumors with AR-independent resistance mechanisms appear to be increasing in frequency. Consequently, there is an urgent need to develop new treatments targeting molecular pathways enriched in lethal prostate cancer. Lysine-specific demethylase 1 (LSD1) is a histone demethylase and an important regulator of gene expression. Here, we show that LSD1 promotes the survival of prostate cancer cells, including those that are castration-resistant, independently of its demethylase function and of the AR. Importantly, this effect is explained in part by activation of a lethal prostate cancer gene network in collaboration with LSD1's binding protein, ZNF217. Finally, that a small-molecule LSD1 inhibitor-SP-2509-blocks important demethylase-independent functions and suppresses castration-resistant prostate cancer cell viability demonstrates the potential of LSD1 inhibition in this disease.}, } @article {pmid29581007, year = {2018}, author = {Howery, KE and Şimşek, E and Kim, M and Rather, PN}, title = {Positive autoregulation of the flhDC operon in Proteus mirabilis.}, journal = {Research in microbiology}, volume = {169}, number = {4-5}, pages = {199-204}, doi = {10.1016/j.resmic.2018.02.005}, pmid = {29581007}, issn = {1769-7123}, mesh = {Feedback, Physiological ; Flagella/*genetics ; Flagellin/genetics ; Gene Expression Regulation, Bacterial/*genetics ; Green Fluorescent Proteins/genetics ; Movement ; Promoter Regions, Genetic/*genetics ; Proteus mirabilis/*genetics ; Trans-Activators/*genetics ; }, abstract = {Using a variety of techniques, we demonstrate the Class I regulator of the flagellar cascade, FlhD4C2, can activate its own expression in Proteus mirabilis. This activation was direct, as the FlhD4C2 protein specifically bound to its promoter region. The expression of bacterial genes under a positive feedback control can exhibit varying levels between cells due to stochastic fluctuations that activate the feedback loop and result in some cells in an "ON" state. Cells containing a chromosomal flhDC::gfp transcriptional fusion exhibited a heterogeneous pattern of expression within the population during growth on agar surfaces and the percentage of cells expressing GFP increased as cells approached swarmer cell differentiation. Disrupting the FlhD4C2 -mediated positive feedback loop significantly reduced the frequency of cells exhibiting GFP expression.}, } @article {pmid29580943, year = {2018}, author = {Xu, B and Santos, SAA and Hinton, BT}, title = {Protein tyrosine kinase 7 regulates extracellular matrix integrity and mesenchymal intracellular RAC1 and myosin II activities during Wolffian duct morphogenesis.}, journal = {Developmental biology}, volume = {438}, number = {1}, pages = {33-43}, pmid = {29580943}, issn = {1095-564X}, support = {R01 HD069654/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Polarity/genetics ; Collagen Type IV/metabolism ; Extracellular Matrix/metabolism ; Extracellular Matrix Proteins/metabolism ; Fluorescent Antibody Technique ; Gene Expression Regulation, Developmental ; Laminin/metabolism ; Male ; Mesoderm/metabolism ; Mice ; Mice, Knockout ; Morphogenesis/*genetics ; Myosin Type II/*metabolism ; Neuropeptides/*metabolism ; Organ Culture Techniques ; Receptor Protein-Tyrosine Kinases/*metabolism ; Sequence Analysis, RNA ; Signal Transduction ; Wolffian Ducts/*embryology ; rac1 GTP-Binding Protein/*metabolism ; }, abstract = {Wolffian duct morphogenesis must be highly coordinated with its specialized function of providing an optimal microenvironment for sperm maturation. Without normal Wolffian duct morphogenesis, male infertility will result. Our previous study showed that mediolateral and radial intercalation of epithelial and mesenchymal cells respectively, were major drivers of ductal elongation and were regulated by protein tyrosine kinase 7 (PTK7), a member of the planar cell polarity (PCP) non-canonical Wnt pathway. To understand the mechanism by which PTK7 regulates cell rearrangement/intercalation, we investigated the integrity of the extracellular matrix (ECM) and the activity of intracellular cytoskeleton mediators following loss of Ptk7. Abnormal assembly of nephronectin, laminin, and collagen IV at the basement membrane and fibrosis-like deposition of fibrilla collagen in the interstitium were observed in Ptk7 knockout Wolffian ducts. Further, the activity levels of RAC1 and myosin II, two cytoskeleton mediators, decreased in the Ptk7 knockout mesenchyme compared to controls. In addition, in-vitro experiments suggested that alterations of ECM and cytoskeleton mediators resulted in changes in Wolffian duct morphogenesis. When in-vitro-cultured Wolffian ducts were treated with collagenase IV, the degree of cross-linked fibrilla collagen was reduced, Wolffian duct elongation and coiling were significantly reduced, and an expanded cyst-like duct was observed. When Wolffian ducts were treated with RAC1 inhibitor NSC23766, mesenchymal fibrilla collagen was disassembled, and Wolffian duct elongation was significantly reduced. Our findings provide evidence that PTK7 regulates ECM integrity and the activity levels of RAC1 and myosin II, which in turn regulates Wolffian duct morphogenesis and therefore, epididymal function.}, } @article {pmid29580884, year = {2018}, author = {Koch, A and Mizrahi, V}, title = {Mycobacterium tuberculosis.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {555-556}, doi = {10.1016/j.tim.2018.02.012}, pmid = {29580884}, issn = {1878-4380}, abstract = {In this infographic, the genetics, phylogeny, physiology, and pathogenesis mechanisms of Mycobacterium tuberculosis are shown. Mycobacterium tuberculosis is the etiological agent of tuberculosis (TB), the leading cause of death due to a single infectious agent, claiming 1.7 million lives in 2016. Of the deaths attributable to TB in 2016, 22% occurred in people coinfected with HIV, and close to 5% of the 10.4 million incident cases of this disease were resistant to at least two of the first-line TB drugs. In this infographic, we describe the fundamental features of the genetics, phylogeny, and physiology of this member of the phylum Actinobacteria, which is associated increasingly with drug resistance mediated by mutations and rearrangements in its single, circular chromosome. We also highlight the key pathogenesis mechanisms employed by this slow-growing, facultative intracellular bacterium, which include avoidance of host cell clearance by arrest of the normal macrophage maturation process.}, } @article {pmid29580663, year = {2018}, author = {Kuchta, R and Choudhury, A and Scholz, T}, title = {Asian Fish Tapeworm: The Most Successful Invasive Parasite in Freshwaters.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {511-523}, doi = {10.1016/j.pt.2018.03.001}, pmid = {29580663}, issn = {1471-5007}, mesh = {*Animal Distribution ; Animals ; Asia ; Cestoda/classification/*physiology ; Cestode Infections/*parasitology ; Europe ; Fish Diseases/*parasitology ; Fishes ; Fresh Water ; Host Specificity/*physiology ; *Introduced Species ; North America ; }, abstract = {The Asian fish tapeworm (AFT), Schyzocotyle acheilognathi, is a notorious and highly successful invasive parasite reported in a wide spectrum of freshwater fishes, and new reports of its spread continue to emerge. To date, no thorough review of its worldwide distribution and host associations is available. In the present work, we collected information from 651 articles up until 2017, from which we updated the number of the hosts to 312 fish species and 11 non-fish species, which is quite unusual among helminths. The AFT has spread to all but one continent (Antarctica). The highest number of records are from North America, followed by Asia and Europe. A key feature of its invasive success is its broad environmental tolerance.}, } @article {pmid29580372, year = {2018}, author = {Zhang, YJ and Liu, XF and Kuang, BZ and Zhang, XY and Zhou, MY and Chen, S}, title = {Neptunicoccus sediminis gen. nov., sp. nov., a member of the family Rhodobacteraceae isolated from the Yellow Sea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1702-1706}, doi = {10.1099/ijsem.0.002728}, pmid = {29580372}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative bacterium, designated strain CY02T, was isolated from sediment of the Yellow Sea. Cells of CY02T were aerobic, coccus or short rods. Growth occurred at 5-42 °C (optimum, 35 °C), pH 6-10 (optimum, 8.0) and 0.5-9.0 % NaCl (optimum, 1.5-3.0 %). Phylogenetic analysis of 16S rRNA gene sequences revealed that CY02T was a member of the family Rhodobacteraceae and exhibited less than 95 % sequence similarities with the closely related type strains of the family Rhodobacteraceae. The genomic DNA G+C content of CY02T was 57.5 mol%. The major respiratory quinone was ubiquinone-10 (Q-10). The polar lipids consisted of phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, three unidentified lipids, one unidentified phospholipid and one unidentified aminolipid. The predominant cellular fatty acids were C18 : 1ω7c (57.6 %), 11-methyl C18 : 1ω7c (22.8 %) and C16 : 0 (10.6 %). Based on the results of morphological, physiological, biochemical, chemotaxonomic, genotypic and phylogenetic analyses, strain CY02T represents a novel species of a novel genus of the family Rhodobacteraceae, for which the name Neptunicoccus sediminis gen. nov., sp. nov. is proposed. The type strain of Neptunicoccus sediminis is CY02T (=CCTCC AB 2015430T=KCTC 42985T=NBRC 111872T=MCCC 1K03518).}, } @article {pmid29580368, year = {2018}, author = {Bassil, NM and Lloyd, JR}, title = {Anaerobacillus isosaccharinicus sp. nov., an alkaliphilic bacterium which degrades isosaccharinic acid.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002721}, pmid = {29580368}, issn = {1466-5034}, abstract = {Strain NB2006T was isolated from an isosaccharinate-degrading, nitrate-reducing enrichment culture in minimal freshwater medium at pH 10. Analysis of the 16S rRNA gene sequence indicated that this strain was most closely related to species of the newly established genus Anaerobacillus. This was supported by phenotypic and metabolic characterisation that showed that NB2006T was rod-shaped, Gram-stain-positive, motile and formed endospores. It was an aerotolerant anaerobe and an obligate alkaliphile that grew at pH 8.5-11, could tolerate up to 6 % (w/v) NaCl, and grew at a temperature between 10 and 40 °C. In addition, it could utilise a number of organic substrates, and was able to reduce nitrate and arsenate. The predominant cellular fatty acids were C16 : 0, C16 : 1ω11c, anteiso-C15 : 0, iso-C15 : 0, C16 : 1ω7c/iso-C15 : 0 2-OH and C14 : 0. The cell wall peptidoglycan contained meso-diaminopimelic acid and the DNA G+C content was 37.7 mol%. In silico DNA-DNA hybridization with the four known species of the genus Anaerobacillus showed 21.8, 21.9, 22.4, and 21.5 % relatedness to Anaerobacillusarseniciselenatis DSM 15340T, Anaerobacilus alkalidiazotrophicus DSM 22531T, Anaerobacillusalkalilacustris DSM 18345T, and Anaerobacillus macyae DSM 16346T, respectively. NB2006T differed from strains of other species of the genus Anaerobacillus in its ability to metabolise isosaccharinate, an alkaline hydrolysis product of cellulose. On the basis of the consensus of phylogenetic and phenotypic analyses, this strain represents a novel species of the genus Anaerobacillus, for which the name Anaerobacillus isosaccharinicus sp. nov. is proposed. The type strain is NB2006T (=DSM 100644T=LMG 30032T).}, } @article {pmid29580324, year = {2018}, author = {López-Hermoso, C and de la Haba, RR and Sánchez-Porro, C and Ventosa, A}, title = {Emended description of Salinivibrio proteolyticus, including Salinivibrio costicola subsp. vallismortis and five new isolates.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1599-1607}, doi = {10.1099/ijsem.0.002716}, pmid = {29580324}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; Puerto Rico ; *Salinity ; Sequence Analysis, DNA ; Spain ; Vibrionaceae/*classification ; *Water Microbiology ; }, abstract = {We carried out a comparative taxonomic study of Salinivibrio proteolyticus and Salinivibrio costicola subsp. vallismortis, as well as of five halophilic strains (IB574, IB872, PR5, PR919 and PR932), isolated from salterns in Spain and Puerto Rico that were closely related to these bacteria. Multilocus sequence analysis of concatenated gyrB, recA, rpoA and rpoD housekeeping genes showed that they constituted a single cluster separate from the other species and subspecies of Salinivibrio. Experimental and in silico DNA-DNA hybridization studies indicated that they are members of the same species, with relatedness of 100-74 % and 97.8-70.0 %, respectively. The average nucleotide identity (ANI) determined for these strains was 99.7-95.6 % for ANIb and 99.7-95.7 % for OrthoANI. However, the ANI values for S. costicolasubsp.vallismortis DSM 8285T with respect to S. costicolasubsp.costicola DSM 11403T and S. costicolasubsp.alcaliphilus DSM 16359T were 78.7 and 78.9 % (ANIb) and 79.4 and 79.4 % (OrthoANI), respectively. The phylogenomic tree based on 1072 concatenated orthologous single-copy core genes confirmed that S. proteolyticus, S. costicolasubsp.vallismortis and the five new isolates constitute a coherent single phylogroup, separated from the other species and subspecies of Salinivibrio. All these data indicate that S. costicolasubsp.vallismortis is a heterotypic synonym of S. proteolyticus and we propose an emended description of this species.}, } @article {pmid29580323, year = {2018}, author = {Wang, NN and Li, CM and Li, YX and Du, ZJ}, title = {Aquimarina celericrescens sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1683-1688}, doi = {10.1099/ijsem.0.002733}, pmid = {29580323}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An orange-coloured, slender rod-shaped, gliding bacterium, designated NS08T, was isolated from coastal water of Xiaoshi Island, Weihai, China (37° 31' 36'' N 122° 00' 58'' E). Cells were Gram-stain-negative, non-spore-forming, non-flagellated, aerobic, catalase-positive and oxidase-negative. Growth occurred at 10-37 °C (optimum 30 °C), in the presence of 1.0-5.0 % (w/v) NaCl (optimum 2.0-3.0 %) and at pH 6.5-9.0 (optimum pH 7.0-7.5). Carotenoid pigments were produced but flexirubin-type pigments were not. The major fatty acids (>10 %) were iso-C15 : 0 and iso-C17 : 0 3-OH. The sole isoprenoid quinone of strain NS08T was menaquinone MK-6 and the DNA G+C content was 39.4 mol%. The polar lipid compositions of strain NS08T and the type strain of the type species of the genus Aquimarina, Aquimarina muelleri KCTC 12285T, were very similar with phosphatidylethanolamine, an unidentified aminolipid and two unknown polar lipids as the major components. A phylogenetic tree based on 16S rRNA gene sequences showed that strain NS08T formed an evolutionary lineage within the genus Aquimarina and shared the highest level of similarity to A. versatilis JCM 19528T (96.0 %) while level to A. muelleri KCTC 12285T was 95.0 %. Phenotypic characteristics distinguished strain NS08T from described members of the genus Aquimarina. On the basis of the evidence presented in this study, strain NS08T represents a novel species of the genus Aquimarina, for which the name Aquimarina celericrescens sp. nov. is proposed. The type strain is NS08T (=KCTC 52897T=MCCC 1H00191T).}, } @article {pmid29580321, year = {2018}, author = {Cole, JK and Morton, BR and Cardamone, HC and Lake, HRR and Dohnalkova, AC and Kim, YM and Kyle, JE and Maezato, Y and Dana, KL and Metz, TO and Romine, MF and Nelson, WC and Lindemann, SR}, title = {Salinivirga fredricksonii gen. nov., sp. nov., a heterotrophic halophile isolated from a photosynthetic mat, a member of a novel lineage (Salinarimonadaceae fam. nov.) within the order Rhizobiales, and reclassification of the genus Salinarimonas Liu et al. 2010 into Salinarimonadaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1591-1598}, doi = {10.1099/ijsem.0.002715}, pmid = {29580321}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics ; Bacterial Typing Techniques ; Base Composition ; Cyanobacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lakes/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Washington ; }, abstract = {A halophilic bacterial strain, HL-109T, was isolated from the unicyanobacterial consortium UCC-O, which was obtained from the photosynthetic mat of Hot Lake (Washington, USA). A polyphasic approach using phenotypic, genotypic and chemotaxonomic data was used to classify the strain within the order Rhizobiales. The organism stained Gram-negative and was a moderate thermophile with a growth optimum of 45 °C. It was obligately aerobic, heterotrophic and halophilic, growing in both NaCl and MgSO4 brines. The novel isolate had a polymorphic cellular morphology of short rods with occasional branching, and cells were monotrichous. The major fatty acids detected were C18 : 1, C18 : 0, C16 : 0 and C18 : cyc. Phylogenetic analysis of the 16S rRNA gene placed the strain in the order Rhizobiales and it shared 94 % identity with the type strain of its nearest relative, Salinarimonas ramus. Morphological, chemotaxonomic and phylogenetic results did not affiliate the novel organism with any of the families in the Rhizobiales; therefore, HL-109T is representative of a new lineage, for which the name Salinivirga fredricksonii gen. nov., sp. nov. is proposed, with the type strain HL-109T (=JCM 31876T=DSM 102886T). In addition, examination of the phylogenetics of strain HL-109T and its nearest relatives, Salinarimonas ramus and Salinarimonasrosea, demonstrates that these halophiles form a clade distinct from the described families of the Rhizobiales. We further propose the establishment of a new family, Salinarimonadaceae fam. nov., to accommodate the genera Salinivirga and Salinarimonas (the type genus of the family).}, } @article {pmid29580317, year = {2018}, author = {Luo, XX and Gao, GB and Xia, ZF and Chen, ZJ and Wan, CX and Zhang, LL}, title = {Streptomyces salilacus sp. nov., an actinomycete isolated from a salt lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1514-1518}, doi = {10.1099/ijsem.0.002703}, pmid = {29580317}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Lakes/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; Streptomyces/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {The taxonomic position of a novel actinomycete, strain TRM 41337T, isolated from sediment of a salt lake, Xiaoerkule Lake, Xinjiang, China, was determined by a polyphasic approach. Strain TRM 41337T grew optimally at 28 °C and in the presence of 1 % (w/v) NaCl. It grew at up to pH 12. The whole-cell sugars of strain TRM 41337T were ribose and xylose. The diagnostic diamino acid contained ll-diaminopimelic acid. The polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositolmannoside and two other unidentified phospholipids. The predominant menaquinones were MK-9(H8), MK-9, MK-9(H4) and MK-9(H6). The major fatty acids were iso-C16 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 1 H. Based on morphological and chemotaxonomic characteristics, the isolate was determined to belong to the genus Streptomyces. The phylogenetic tree based on its nearly complete 16S rRNA gene sequence (1498 nt) with representative strains showed that the strain consistently falls into a distinct phyletic lineage together with Streptomyces barkulensis DSM 42082T (97.48 % similarity) and a subclade consisting of Streptomyces fenghuangensis GIMN 4.003T (97.20 %), Streptomyces macrosporus NBRC 14748T (97.14 %) and Streptomyces radiopugnans R97T (97.01 %). On the basis of these data, strain TRM 41337T should be designated as a representative of a novel species of the genus Streptomyces, for which the name Streptomyces salilacus sp. nov. is proposed. The type strain is TRM 41337T (=CCTCC AA 2015030T=KCTC 39726T).}, } @article {pmid29580295, year = {2018}, author = {Pahwa, P and Rana, M and Pickett, W and Karunanayake, CP and Amin, K and Koehncke, N and Elliot, V and Hagel, L and Lawson, J and Rennie, D and Kirychuk, S and Janzen, B and Dyck, R and Dosman, J}, title = {Correction to: Cohort profile: the Saskatchewan Rural Health Study-adult component.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {191}, pmid = {29580295}, issn = {1756-0500}, abstract = {Following publication of the original article [1] the authors notified Production that the names of three authors-Valerie Elliot, Louise Hagel, and Roland Dyck-had been unintentionally omitted in the final online version of the manuscript. The corrected author list is shown in this Correction.}, } @article {pmid29580290, year = {2018}, author = {Zakany, J and Duboule, D}, title = {Rescue of an aggressive female sexual courtship in mice by CRISPR/Cas9 secondary mutation in vivo.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {193}, pmid = {29580290}, issn = {1756-0500}, support = {310030B_138662//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/ ; 232790//European Research Council ()/ ; 588029//European Research Council ()/ ; }, mesh = {Animals ; *CRISPR-Cas Systems ; Cholecystokinin/genetics ; *Courtship ; Female ; Gene Expression ; Glutamate Decarboxylase/genetics ; Homeodomain Proteins/*genetics ; In Situ Hybridization, Fluorescence ; Male ; Mice ; *Mutation ; Neocortex/cytology/metabolism/physiology ; *Sequence Deletion ; Transcription Factors/genetics ; }, abstract = {OBJECTIVE: We had previously reported a mouse line carrying the Atypical female courtship (HoxD Afc) allele, where an ectopic accumulation of Hoxd10 transcripts was observed in a sparse population of cells in the adult isocortex, as a result of a partial deletion of the HoxD gene cluster. Female mice carrying this allele displayed an exacerbated paracopulatory behavior, culminating in a severe mutilation of the studs' external genitals. To unequivocally demonstrate that this intriguing phenotype was indeed caused by an illegitimate function of the HOXD10 protein, we use CRISPR/Cas9 technology to induce a microdeletion into the homeobox of the Hoxd10 gene in cis with the HoxD Afc allele.

RESULTS: Females carrying this novel HoxDDel(1-9)d10hd allele no longer mutilate males. We conclude that a brain malfunction leading to a severe pathological behavior can be caused by the mere binding to DNA of a transcription factor expressed ectopically. We also show that in HoxD Afc mice, Hoxd10 was expressed in cells containing glutamate decarboxylase (Gad1) and Cholecystokinin (Cck) transcripts, corroborating our proposal that a small fraction of GABAergic neurons in adult hippocampus may participate to some aspects of female courtship.}, } @article {pmid29580289, year = {2018}, author = {Gagné-Thivierge, C and Kukavica-Ibrulj, I and Filion, G and Dekimpe, V and Tan, SGE and Vincent, AT and Déziel, É and Levesque, RC and Charette, SJ}, title = {A multi-host approach to identify a transposon mutant of Pseudomonas aeruginosa LESB58 lacking full virulence.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {198}, pmid = {29580289}, issn = {1756-0500}, support = {MOP-142466//Institute of Infection and Immunity/ ; RGPIN-2014-04595//Canadian Network for Research and Innovation in Machining Technology, Natural Sciences and Engineering Research Council of Canada/ ; 2610//Cystic Fibrosis Canada/ ; }, mesh = {Animals ; DNA Transposable Elements ; Dictyostelium/microbiology ; Drosophila melanogaster/microbiology ; Female ; Host-Pathogen Interactions ; Lung/microbiology ; Mutagenesis, Insertional ; *Mutation ; Pseudomonas Infections/*microbiology ; Pseudomonas aeruginosa/*genetics/*pathogenicity ; Rats, Sprague-Dawley ; Species Specificity ; Virulence/genetics ; }, abstract = {OBJECTIVE: Pseudomonas aeruginosa is an opportunistic bacterial pathogen well known to cause chronic lung infections in individuals with cystic fibrosis (CF). Some strains adapted to this particular niche show distinct phenotypes, such as biofilm hyperproduction. It is necessary to study CF clinical P. aeruginosa isolates, such as Liverpool Epidemic Strains (LES), to acquire a better understanding of the key genes essential for in vivo maintenance and the major virulence mechanisms involved in CF lung infections. Previously, a library of 9216 mutants of the LESB58 strain were generated by signature-tagged mutagenesis (STM) and screened in the rat model of chronic lung infection, allowing the identification of 163 STM mutants showing defects in in vivo maintenance.

RESULTS: In the present study, these 163 mutants were successively screened in two additional surrogate host models (the amoeba and the fruit fly). The STM PALES_11731 mutant was the unique non-virulent in the three hosts. A competitive index study in rat lungs confirmed that the mutant was 20-fold less virulent than the wild-type strain. This study demonstrated the pertinence to use a multi-host approach to study the genetic determinants of P. aeruginosa strains infecting CF patients.}, } @article {pmid29580274, year = {2018}, author = {Guiedem, E and Ikomey, GM and Nkenfou, C and Walter, PE and Mesembe, M and Chegou, NN and Jacobs, GB and Okomo Assoumou, MC}, title = {Chronic obstructive pulmonary disease (COPD): neutrophils, macrophages and lymphocytes in patients with anterior tuberculosis compared to tobacco related COPD.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {192}, pmid = {29580274}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Case-Control Studies ; Female ; Humans ; Lymphocytes/*cytology/immunology ; Macrophages/*cytology/immunology ; Male ; Middle Aged ; Neutrophils/*cytology/immunology ; Pulmonary Disease, Chronic Obstructive/etiology/*immunology ; Smoking/adverse effects ; Sputum/cytology/immunology ; Tobacco ; Tuberculosis, Pulmonary/*immunology ; }, abstract = {OBJECTIVE: The inflammatory profile of chronic obstructive pulmonary disease (COPD) related to tobacco is known in certain studies while that of the post tuberculosis form is not yet known. This study aimed to evaluate the levels of neutrophils, macrophages and lymphocytes cells in sputum of COPD patients with history of smoking or anterior tuberculosis. Enumeration of cells in samples was analyzed using standard microscopy.

RESULTS: We enrolled 92 participants, 46 (50%) were COPD subjects comprising 22 (47.83%) smokers and 24 (52.17%) with anterior tuberculosis while 46 (50%) healthy persons constituted the control group. The levels of neutrophils, lymphocytes and monocytes were statistically higher in COPD patients compared to the control group with p-values of 0.0001 respectively. Neutrophils levels were higher in COPD patients with history of tobacco than in COPD patients with anterior tuberculosis with a mean rate of 4.72 × 106/ml and 2.48 × 106/ml respectively (p = 0.04). The monocytes and lymphocytes levels were not statistically different between the two sub-groups of COPD patients with p-value of 0.052 and 0.91 respectively. Neutrophils are the only inflammatory cells that were significantly higher in COPD patients with history of smoking as compared to COPD patients with anterior tuberculosis.}, } @article {pmid29580273, year = {2018}, author = {Komagamine, J and Hagane, K}, title = {Effect of total exemption from medical service co-payments on potentially inappropriate medication use among elderly ambulatory patients in a single center in Japan: a retrospective cross-sectional study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {199}, pmid = {29580273}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Benzodiazepines/*economics/therapeutic use ; Cross-Sectional Studies ; *Drug Costs ; Female ; Health Care Costs/statistics & numerical data ; Humans ; Inappropriate Prescribing/*economics/statistics & numerical data ; Japan ; Male ; Potentially Inappropriate Medication List/*economics/statistics & numerical data ; Practice Patterns, Physicians'/economics/statistics & numerical data ; Retrospective Studies ; }, abstract = {OBJECTIVE: The effect of total exemption from medical service co-payments on drug prescribing practices has not been extensively evaluated. We conducted a retrospective cross-sectional study to evaluate the effect of total exemption from medical service co-payments on potentially inappropriate medication (PIM) and benzodiazepine use in elderly ambulatory patients. We defined PIM based on the Beers Criteria.

RESULTS: Six hundred seventy-one consecutive patients aged 65 years or older who routinely visited internal medicine physicians were included. Their mean age was 75.7 years, and 342 (51.0%) patients were men. The proportions of patients taking any PIMs or benzodiazepines were 37.7% and 16.2%, respectively. Of all patients, 62 (9.2%) were totally exempt from medical service co-payments. The patients who were totally exempt from medical service co-payments showed a significantly increased risk of PIM (OR 2.16, 95% CI 1.28-3.66) or benzodiazepine use (OR 2.12, 95% CI 1.16-3.87) compared with patients who were not. These associations did not change after adjusting for age, gender, comorbidities and polypharmacy. These findings should be confirmed in other settings or hospitals in Japan.}, } @article {pmid29580270, year = {2018}, author = {Torimoto, K and Matsumoto, Y and Gotoh, D and Morizawa, Y and Miyake, M and Samma, S and Tanaka, N and Hirayama, A and Fujimoto, K}, title = {Overactive bladder induces transient hypertension.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {196}, pmid = {29580270}, issn = {1756-0500}, mesh = {Aged ; Aged, 80 and over ; Blood Pressure/*physiology ; Humans ; Hypertension/etiology/*physiopathology ; Male ; Middle Aged ; Surveys and Questionnaires ; Urinary Bladder, Overactive/complications/*physiopathology ; Urination/*physiology ; }, abstract = {OBJECTIVES: Several studies have shown the relationship between lower urinary tract symptoms and autonomic imbalance. We investigated the relationship between detrusor overactivity (DO) or urgency, and transient increase in blood pressure as a type of hypertension related to sympathetic hyperactivity. Study 1: we enrolled 14 male patients with DO and 10 without DO. We measured the overactive bladder symptom score (OABSS) and blood pressure during cystometry. Study 2: we enrolled 14 men patients with overactive bladder (OAB) and 8 without OAB. We measured OABSS and blood pressure using a 24-h ambulatory device.

RESULTS: Study 1: the mean systolic pressure was significantly higher at urgency or SDV than at the other measurement points in the DO group (161.3 ± 23.2 vs. 134.5 ± 16.3, 137.8 ± 15.3, or 139.5 ± 14.8 mmHg). Study 2: the mean systolic pressure was significantly higher at the measurement points before micturition than at the points unrelated to micturition in the OAB group (159.7 ± 24.9 vs. 124.9 ± 13.8 mmHg). In conclusion, DO or urgency induces a transient increase of blood pressure, suggesting that OAB induces a type of hypertension before micturition.}, } @article {pmid29580266, year = {2018}, author = {Lian, BSX and Yek, AEH and Shuvas, H and Abdul Rahman, SF and Muniandy, K and Mohana-Kumaran, N}, title = {Synergistic anti-proliferative effects of combination of ABT-263 and MCL-1 selective inhibitor A-1210477 on cervical cancer cell lines.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {197}, pmid = {29580266}, issn = {1756-0500}, support = {203/PBIOLOGI/6711355//Ministry of Higher Education, Malaysia/ ; 203/PBIOLOGI/6711541//Ministry of Higher Education, Malaysia/ ; 304/PBIOLOGI/6313312//Universiti Sains Malaysia/ ; 304/PBIOLOGI/650828/M121//Majlis Kanser Nasional/ ; }, mesh = {Aniline Compounds/*pharmacology ; Antineoplastic Agents/pharmacology ; Cell Line, Tumor ; Cell Proliferation/*drug effects ; Drug Synergism ; Female ; Humans ; Indoles/*pharmacology ; Myeloid Cell Leukemia Sequence 1 Protein/*antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-bcl-2/antagonists & inhibitors/metabolism ; Sulfonamides/*pharmacology ; Uterine Cervical Neoplasms/metabolism/pathology ; bcl-X Protein/antagonists & inhibitors/metabolism ; }, abstract = {OBJECTIVE: There are number of studies which report that BCL-2 anti-apoptotic proteins (e.g. BCL-2, BCL-XL, and MCL-1) are highly expressed in cervical cancer tissues compared to the normal cervical epithelia. Despite these reports, targeting these proteins for cervical cancer treatment has not been explored extensively. BH3-mimetics that inhibit specific BCL-2 anti-apoptotic proteins may hold encouraging treatment outcomes for cervical cancer management. Hence, the aim of this pilot study is to investigate the sensitivity of cervical cancer cell lines to combination of two BH3-mimetics namely ABT-263 which selectively inhibits BCL-2, BCL-XL and BCL-w and A-1210477, a selective MCL-1 inhibitor.

RESULTS: We report that combination of A-1210477 and ABT-263 exhibited synergistic effects on all cervical cancer cell lines tested. Drug sensitization studies revealed that A-1210477 sensitised the cervical cancer cell lines SiHa and CaSki to ABT-263 by 11- and fivefold, respectively. Sensitization also occurred in the opposite direction whereby ABT-263 sensitised SiHa and CaSki to A-1210477 by eightfold. This report shows that combination of ABT-263 and A-1210477 could be a potential treatment strategy for cervical cancer. Extensive drug mechanistic studies and drug sensitivity studies in physiological models are necessary to unleash the prospect of this combination for cervical cancer therapy.}, } @article {pmid29580265, year = {2018}, author = {Nakajima, K and Kanda, E and Suwa, K}, title = {Unexpected association between subclinical hearing loss and restorative sleep in a middle-aged and elderly Japanese population.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {195}, pmid = {29580265}, issn = {1756-0500}, mesh = {Adult ; Aged ; Asian Continental Ancestry Group ; Databases, Factual/*statistics & numerical data ; Female ; Hearing Loss/epidemiology/ethnology/*physiopathology ; Humans ; Japan/epidemiology ; Male ; Middle Aged ; Prevalence ; Risk Factors ; Sleep/*physiology ; *Surveys and Questionnaires ; Time Factors ; }, abstract = {OBJECTIVE: Hearing loss may be associated with certain sleep abnormalities. We recently reported that subclinical hearing loss (SHL) was more prevalent in individuals in a broad Japanese population who slept longer than 8 h; however, the underlying mechanism was unknown. Therefore, we investigated the association between SHL and self-reported restorative sleep (RS), assessed by questionnaire, in a database of 33,888 Japanese aged 40-69 years without overt or diagnosed hearing loss (20,225 men, 13,663 women).

RESULTS: The proportion of individuals with RS (more than half of the subjects) was significantly higher in the group with bilateral than with unilateral SHL at 4000 Hz and intact hearing; however, that was not the case at 1000 Hz, independent of age (P < 0.0001, two-way analysis of variance). Multivariate logistic regression analysis showed that bilateral SHL at 4000 Hz, but not at 1000 Hz, was significantly associated with RS. This relationship was independent of potential relevant confounders, including age, sex, and cardiometabolic risk factors. The present study extends our earlier work by revealing an unexpected association between early hearing impairment and satisfactory sleep in a middle-aged and elderly population. This association requires further confirmation regarding the possible underlying mechanism and clinical relevance.}, } @article {pmid29580263, year = {2018}, author = {Hoebel, J and Kuntz, B and Moor, I and Kroll, LE and Lampert, T}, title = {Post-millennial trends of socioeconomic inequalities in chronic illness among adults in Germany.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {200}, pmid = {29580263}, issn = {1756-0500}, mesh = {Adult ; Aged ; Chronic Disease/epidemiology/*therapy ; Cross-Sectional Studies ; Female ; Germany/epidemiology ; *Health Status Disparities ; Health Surveys/methods/statistics & numerical data ; Humans ; Male ; Middle Aged ; Prevalence ; Social Class ; *Socioeconomic Factors ; }, abstract = {OBJECTIVE: Time trends in health inequalities have scarcely been studied in Germany as only few national data have been available. In this paper, we explore trends in socioeconomic inequalities in the prevalence of chronic illness using Germany-wide data from four cross-sectional health surveys conducted between 2003 and 2012 (n = 54,197; ages 25-69 years). We thereby expand a prior analysis on post-millennial inequality trends in behavioural risk factors by turning the focus to chronic illness as the outcome measure. The regression-based slope index of inequality (SII) and relative index of inequality (RII) were calculated to estimate the extent of absolute and relative socioeconomic inequalities in chronic illness, respectively.

RESULTS: The results for men revealed a significant increase in the extent of socioeconomic inequalities in chronic illness between 2003 and 2012 on both the absolute and relative scales (SII2003 = 0.06, SII2012 = 0.17, p-trend = 0.013; RII2003 = 1.18, RII2012 = 1.57, p-trend = 0.013). In women, similar increases in socioeconomic inequalities in chronic illness were found (SII2003 = 0.05, SII2012 = 0.14, p-trend = 0.022; RII2003 = 1.14, RII2012 = 1.40, p-trend = 0.021). Whereas in men this trend was driven by an increasing prevalence of chronic illness in the low socioeconomic group, the trend in women was predominantly the result of a declining prevalence in the high socioeconomic group.}, } @article {pmid29580256, year = {2018}, author = {Weldemariam, S and Kiros, A and Welday, M}, title = {Utilization of institutional delivery service and associated factors among mothers in North West Ethiopian.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {194}, pmid = {29580256}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Delivery, Obstetric/*statistics & numerical data ; Ethiopia ; Female ; Home Childbirth/statistics & numerical data ; Humans ; Male ; Maternal Health Services/*statistics & numerical data ; Middle Aged ; Mothers/statistics & numerical data ; Pregnancy ; Prenatal Care/*statistics & numerical data ; *Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to assess institutional delivery and its associated factors in Benishangul-Gumez region, North-West of Ethiopia. The data were obtained at community level in a single survey within 1 month and there is no continuation of this study or previously published part elsewhere.

RESULTS: Among the 428 eligible respondents recruited for this study, 427 of them responded completely to the interview, giving a response rate of 99.8%. Of the total (427) respondents, 51.1% women delivered the recent child at health facility in the 12 months preceding the survey. Among the common reasons for home delivery were, labour was urgent (25.8%), home birth was usual habit for them (23.9%) and distance to health center was too far. Age (AOR = 3.4, 95% CI 1.46, 7.97), husband occupation (AOR = 5.16, 95% CI 1.74, 15.31), frequency of antenatal care visit (AOR = 3.34, 95% CI 1.88, 5.94) and maternal knowledge on danger signs of pregnancy and delivery (AOR = 7.18, 95% CI 3.77, 13.66) were significantly associated factors with institutional delivery. Although, the prevalence of institutional delivery has improved when compared to previous reports, strategic modification is important to increase health facility delivery.}, } @article {pmid29580229, year = {2018}, author = {Li, HS and Zou, SJ and De Clercq, P and Pang, H}, title = {Population admixture can enhance establishment success of the introduced biological control agent Cryptolaemus montrouzieri.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {36}, pmid = {29580229}, issn = {1471-2148}, mesh = {Animals ; *Biological Control Agents ; China ; Coleoptera/*genetics/growth & development ; Genetic Fitness ; *Genetics, Population ; Life Cycle Stages ; Phenotype ; Reproduction ; }, abstract = {BACKGROUND: Introduced biological control agents have opportunities of population admixture through multiple introductions in the field. However, the importance of population admixture for their establishment success often remains unclear. Previous studies based on genetic markers have suggested a history of population admixture in the predatory ladybird Cryptolaemus montrouzieri Mulsant in China.

RESULTS: We tested whether population admixture may lead to fitness changes under laboratory conditions. We first found no mating barrier or strong bias between two parental populations, despite their differences in genetics and phenotypes. Then, our experimental evidence supported the hypothesis that admixed populations have a higher potential of establishment success, due to their superior reproductive ability, and hunger and cold tolerance inherited from one of the parental populations.

CONCLUSIONS: We suggest that population admixture can be a breeding method to improve the performance of biological control agents, particularly when used in a classical biological control approach, but that consequences for potential invasiveness need to be considered.}, } @article {pmid29580224, year = {2018}, author = {Zeng, Z and Sun, H and Vainio, EJ and Raffaello, T and Kovalchuk, A and Morin, E and Duplessis, S and Asiegbu, FO}, title = {Intraspecific comparative genomics of isolates of the Norway spruce pathogen (Heterobasidion parviporum) and identification of its potential virulence factors.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {220}, pmid = {29580224}, issn = {1471-2164}, support = {276862//Academy of Finland/International ; }, mesh = {Basidiomycota/*genetics/*isolation & purification ; *Genome, Viral ; Genomics/*methods ; Picea/*microbiology ; Plant Diseases/*microbiology ; Polymorphism, Single Nucleotide ; Virulence Factors/*genetics ; }, abstract = {BACKGROUND: Heterobasidion parviporum is an economically most important fungal forest pathogen in northern Europe, causing root and butt rot disease of Norway spruce (Picea abies (L.) Karst.). The mechanisms underlying the pathogenesis and virulence of this species remain elusive. No reference genome to facilitate functional analysis is available for this species.

RESULTS: To better understand the virulence factor at both phenotypic and genomic level, we characterized 15 H. parviporum isolates originating from different locations across Finland for virulence, vegetative growth, sporulation and saprotrophic wood decay. Wood decay capability and latitude of fungal origins exerted interactive effects on their virulence and appeared important for H. parviporum virulence. We sequenced the most virulent isolate, the first full genome sequences of H. parviporum as a reference genome, and re-sequenced the remaining 14 H. parviporum isolates. Genome-wide alignments and intrinsic polymorphism analysis showed that these isolates exhibited overall high genomic similarity with an average of at least 96% nucleotide identity when compared to the reference, yet had remarkable intra-specific level of polymorphism with a bias for CpG to TpG mutations. Reads mapping coverage analysis enabled the classification of all predicted genes into five groups and uncovered two genomic regions exclusively present in the reference with putative contribution to its higher virulence. Genes enriched for copy number variations (deletions and duplications) and nucleotide polymorphism were involved in oxidation-reduction processes and encoding domains relevant to transcription factors. Some secreted protein coding genes based on the genome-wide selection pressure, or the presence of variants were proposed as potential virulence candidates.

CONCLUSION: Our study reported on the first reference genome sequence for this Norway spruce pathogen (H. parviporum). Comparative genomics analysis gave insight into the overall genomic variation among this fungal species and also facilitated the identification of several secreted protein coding genes as putative virulence factors for the further functional analysis. We also analyzed and identified phenotypic traits potentially linked to its virulence.}, } @article {pmid29580219, year = {2018}, author = {Hebert, PDN and Braukmann, TWA and Prosser, SWJ and Ratnasingham, S and deWaard, JR and Ivanova, NV and Janzen, DH and Hallwachs, W and Naik, S and Sones, JE and Zakharov, EV}, title = {A Sequel to Sanger: amplicon sequencing that scales.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {219}, pmid = {29580219}, issn = {1471-2164}, mesh = {Animals ; Arthropods/classification/*genetics ; Genetic Variation ; High-Throughput Nucleotide Sequencing/*methods ; Polymerase Chain Reaction/*methods ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Although high-throughput sequencers (HTS) have largely displaced their Sanger counterparts, the short read lengths and high error rates of most platforms constrain their utility for amplicon sequencing. The present study tests the capacity of single molecule, real-time (SMRT) sequencing implemented on the SEQUEL platform to overcome these limitations, employing 658 bp amplicons of the mitochondrial cytochrome c oxidase I gene as a model system.

RESULTS: By examining templates from more than 5000 species and 20,000 specimens, the performance of SMRT sequencing was tested with amplicons showing wide variation in GC composition and varied sequence attributes. SMRT and Sanger sequences were very similar, but SMRT sequencing provided more complete coverage, especially for amplicons with homopolymer tracts. Because it can characterize amplicon pools from 10,000 DNA extracts in a single run, the SEQUEL can reduce greatly reduce sequencing costs in comparison to first (Sanger) and second generation platforms (Illumina, Ion).

CONCLUSIONS: SMRT analysis generates high-fidelity sequences from amplicons with varying GC content and is resilient to homopolymer tracts. Analytical costs are low, substantially less than those for first or second generation sequencers. When implemented on the SEQUEL platform, SMRT analysis enables massive amplicon characterization because each instrument can recover sequences from more than 5 million DNA extracts a year.}, } @article {pmid29580217, year = {2018}, author = {Nasher, F and Förster, S and Yildirim, EC and Grandgirard, D and Leib, SL and Heller, M and Hathaway, LJ}, title = {Foreign peptide triggers boost in pneumococcal metabolism and growth.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {23}, pmid = {29580217}, issn = {1471-2180}, abstract = {BACKGROUND: Nonencapsulated Streptococcus pneumoniae bacteria are successful colonizers of the human nasopharynx and often possess genes aliB-like ORF 1 and 2 in place of capsule genes. AliB-like ORF 2 binds peptide FPPQSV, found in Prevotella species, resulting in enhanced colonization. How this response is mediated is so far unknown.

RESULTS: Here we show that the peptide increases expression of genes involved in release of host carbohydrates, carbohydrate uptake and carbohydrate metabolism. In particular, the peptide increased expression of 1,5-anhydro-D-fructose reductase, a metabolic enzyme of an alternative starch and glycogen degrading pathway found in many organisms, in both transcriptomic and proteomic data. The peptide enhanced pneumococcal growth giving a competitive advantage to a strain with aliB-like ORF 2, over its mutant lacking the gene. Possession of aliB-like ORF 2 did not affect release of inflammatory cytokine CXCL8 from epithelial cells in culture and the nonencapsulated wild type strain was not able to establish disease or inflammation in an infant rat model of meningitis.

CONCLUSIONS: We propose that AliB-like ORF 2 confers an advantage in colonization by enhancing carbohydrate metabolism resulting in a boost in growth. This may explain the widespread presence of aliB-like ORF 2 in the nonencapsulated pneumococcal population in the human nasopharynx.}, } @article {pmid29580214, year = {2018}, author = {Zhan, LP and Peng, DL and Wang, XL and Kong, LA and Peng, H and Liu, SM and Liu, Y and Huang, WK}, title = {Priming effect of root-applied silicon on the enhancement of induced resistance to the root-knot nematode Meloidogyne graminicola in rice.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {50}, pmid = {29580214}, issn = {1471-2229}, support = {31571986//National Natural Sciences Foundation of China/ ; 2013CB127502//National Basic Research Program of China/ ; }, mesh = {Animals ; Lignin/metabolism ; Oryza/*drug effects/*parasitology ; Plant Diseases/parasitology/*prevention & control ; Plant Roots/*drug effects/*parasitology ; Silicon/*pharmacology ; Tylenchoidea/drug effects/*pathogenicity ; }, abstract = {BACKGROUND: Silicon (Si) can confer plant resistance to both abiotic and biotic stress. In the present study, the priming effect of Si on rice (Oryza sativa cv Nipponbare) against the root-knot nematode Meloidogyne graminicola and its histochemical and molecular impact on plant defense mechanisms were evaluated.

RESULTS: Si amendment significantly reduced nematodes in rice roots and delayed their development, while no obvious negative effect on giant cells was observed. Increased resistance in rice was correlated with higher transcript levels of defense-related genes (OsERF1, OsEIN2 and OsACS1) in the ethylene (ET) pathway. Si amendment significantly reduced nematode numbers in rice plants with enhanced ET signaling but had no effect in plants deficient in ET signaling, indicating that the priming effects of Si were dependent on the ET pathway. A higher deposition of callose and accumulation of phenolic compounds were observed in rice roots after nematode attack in Si-amended plants than in the controls.

CONCLUSION: These findings indicate that the priming effect may partially depend on the production of phenolic compounds and hydrogen peroxide. Further research is required to model the ethylene signal transduction pathway that occurs in the Si-plant-nematode interaction system and gain a better understanding of Si-induced defense in rice.}, } @article {pmid29580211, year = {2018}, author = {Cui, Y and Zhu, Y and Lin, Y and Chen, L and Feng, Q and Wang, W and Xiang, H}, title = {New insight into the mechanism underlying the silk gland biological process by knocking out fibroin heavy chain in the silkworm.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {215}, pmid = {29580211}, issn = {1471-2164}, support = {31371286//National Natural Science Foundation of China/International ; 31330071//National Natural Science Foundation of China/International ; }, mesh = {Animals ; Autophagy ; Bombyx/genetics/*metabolism ; CRISPR-Cas Systems ; Fibroins/antagonists & inhibitors/genetics/*metabolism ; High-Throughput Nucleotide Sequencing ; Insect Proteins/genetics/*metabolism ; Proteasome Endopeptidase Complex ; Silk/*chemistry ; *Transcriptome ; }, abstract = {BACKGROUND: Exploring whether and how mutation of silk protein contributes to subsequent re-allocation of nitrogen, and impacts on the timing of silk gland degradation, is important to understand silk gland biology. Rapid development and wide application of genome editing approach in the silkworm provide us an opportunity to address these issues.

RESULTS: Using CRISPR/Cas9 system, we successfully performed genome editing of Bmfib-H. The loss-of-function mutations caused naked pupa and thin cocoon mutant phenotypes. Compared with the wild type, the posterior silk gland of mutant showed obviously degraded into fragments in advance of programmed cell death of silk gland cells. Comparative transcriptomic analyses of silk gland at the fourth day of the fifth instar larval stage(L5D4)identified 1456 differential expressed genes (DEGs) between posterior silk gland (PSG) and mid silk gland (MSG) and 1388 DEGs between the mutant and the wild type. Hierarchical clustering of all the DEGs indicated a remarkable down-regulated and an up-regulated gene clade in the mutant silk glands, respectively. Down-regulated genes were overrepresented in the pathways involved in cancer, DNA replication and cell proliferation. Intriguingly, up-regulated DEGs are significantly enriched in the proteasome. By further comparison on the transcriptome of MSG and PSG between the wild type and the mutant, we consistently observed that up-regulated DEGs in the mutant PSG were enriched in protein degrading activity and proteasome. Meantime, we observed a series of up-regulated genes involved in autophagy. Since these protein degradation processes would be normally occur after the spinning time, the results suggesting that these progresses were activated remarkably ahead of schedule in the mutant.

CONCLUSIONS: Accumulation of abnormal fib-H protein might arouse the activation of proteasomes as well as autophagy process, to promote the rapid degradation of such abnormal proteins and the silk gland cells. Our study therefore proposes a subsequent process of protein and partial cellular degradation caused by mutation of silk protein, which might be helpful for understanding its impact of the silk gland biological process, and further exploration the re-allocation of nitrogen in the silkworm.}, } @article {pmid29580210, year = {2018}, author = {Herb, BR and Shook, MS and Fields, CJ and Robinson, GE}, title = {Defense against territorial intrusion is associated with DNA methylation changes in the honey bee brain.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {216}, pmid = {29580210}, issn = {1471-2164}, support = {R21 MH107962/MH/NIMH NIH HHS/United States ; R21-MH107962/NH/NIH HHS/United States ; SFLife 291812//Simons Foundation/International ; }, mesh = {Aggression ; Animals ; Bees/genetics/*physiology ; Behavior, Animal ; Biological Evolution ; Brain/physiology ; DNA Methylation ; Epigenesis, Genetic ; Gene Expression Regulation ; Genome ; Insect Proteins/*genetics ; Territoriality ; }, abstract = {BACKGROUND: Aggression is influenced by individual variation in temperament as well as behavioral plasticity in response to adversity. DNA methylation is stably maintained over time, but also reversible in response to specific environmental conditions, and may thus be a neuromolecular regulator of both of these processes. A previous study reported DNA methylation differences between aggressive Africanized and gentle European honey bees. We investigated whether threat-induced aggression altered DNA methylation profiles in the honey bee brain in response to a behavioral stimulus (aggression-provoking intruder bee or inert control). We sampled five minutes and two hours after stimulus exposure to examine the effect of time on epigenetic profiles of aggression.

RESULTS: There were DNA methylation differences between aggressive and control bees for individual cytosine-guanine dinucleotides (CpGs) across the genome. Eighteen individual CpG sites showed significant difference between aggressive and control bees 120 min post stimulus. For clusters of CpGs, we report four genomic regions differentially methylated between aggressive and control bees at the 5-min time point, and 50 regions differentially methylated at the120-minute time point following intruder exposure. Differential methylation occurred at genes involved in neural plasticity, chromatin remodeling and hormone signaling. Additionally, there was a significant overlap of differential methylation with previously published epigenetic differences that distinguish aggressive Africanized and gentle European honey bees, suggesting an evolutionarily conserved use of brain DNA methylation in the regulation of aggression. Lastly, we identified individually statistically suggestive CpGs that as a group were significantly associated with differentially expressed genes underlying aggressive behavior and also co-localize with binding sites of transcription factors involved in neuroplasticity or neurodevelopment.

CONCLUSIONS: There were DNA methylation differences in the brain associated with response to an intruder. These differences increased in number a few hours after the initial exposure and overlap with previously reported aggression-associated genes and neurobiologically relevant transcription factor binding sites. Many DNA methylation differences that occurred in association with the expression of aggression in real time also exist between Africanized bees and European bees, suggesting an evolutionarily conserved role for epigenetic regulation in aggressive behavior.}, } @article {pmid29580208, year = {2018}, author = {Premnath, P and Reck, M and Wittstein, K and Stadler, M and Wagner-Döbler, I}, title = {Screening for inhibitors of mutacin synthesis in Streptococcus mutans using fluorescent reporter strains.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {24}, pmid = {29580208}, issn = {1471-2180}, abstract = {BACKGROUND: Within the polymicrobial dental plaque biofilm, bacteria kill competitors by excreting mixtures of bacteriocins, resulting in improved fitness and survival. Inhibiting their bacteriocin synthesis might therefore be a useful strategy to eliminate specific pathogens. We used Streptococcus mutans, a highly acidogenic inhabitant of dental plaque, as a model and searched for natural products that reduced mutacin synthesis. To this end we fused the promoter of mutacin VI to the GFP+ gene and integrated the construct into the genome of S. mutans UA159 by single homologous recombination.

RESULTS: The resulting reporter strain 423p - gfp + was used to screen 297 secondary metabolites from different sources, mainly myxobacteria and fungi, for their ability to reduce the fluorescence of the fully induced reporter strain by > 50% while growth was almost unaffected (> 90% of control). Seven compounds with different chemical structures and different modes of action were identified. Erinacine C was subsequently validated and shown to inhibit transcription of all three mutacins of S. mutans. The areas of the inhibition zones of the sensor strains S. sanguinis and Lactococcus lactis were reduced by 35% to 61% in comparison to controls in the presence of erinacine C, demonstrating that the amount of active mutacins in the culture supernatants of S. mutans was reduced. Erinacines are cyathane diterpenes that were extracted from cultures of the edible mushroom Hericium erinaceus. They have anti-inflammatory, antimicrobial and neuroprotective effects. For erinacine C, a new biological activity was found here.

CONCLUSIONS: We demonstrate the successful development of a whole-cell fluorescent reporter for the screening of natural compounds and report that erinacine C suppresses mutacin synthesis in S. mutans without affecting cell viability.}, } @article {pmid29580206, year = {2018}, author = {Schumacher, J and Herlyn, H}, title = {Correlates of evolutionary rates in the murine sperm proteome.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {35}, pmid = {29580206}, issn = {1471-2148}, support = {HE 3487/3-1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Expression Regulation ; Gene Ontology ; Genetic Pleiotropy ; Introns/genetics ; Male ; Mice ; Molecular Sequence Annotation ; Open Reading Frames/genetics ; Organ Specificity/genetics ; Phylogeny ; Proteome/*metabolism ; Spermatozoa/*metabolism ; Statistics, Nonparametric ; Untranslated Regions/genetics ; }, abstract = {BACKGROUND: Protein-coding genes expressed in sperm evolve at different rates. To gain deeper insight into the factors underlying this heterogeneity we examined the relative importance of a diverse set of previously described rate correlates in determining the evolution of murine sperm proteins.

RESULTS: Using partial rank correlations we detected several major rate indicators: Phyletic gene age, numbers of protein-protein interactions, and survival essentiality emerged as particularly important rate correlates in murine sperm proteins. Tissue specificity, numbers of paralogs, and untranslated region lengths also correlate significantly with sperm genes' evolutionary rates, albeit to a lesser extent. Multifunctionality, coding sequence or average intron lengths, and mean expression level have insignificant or virtually no independent effects on evolutionary rates in murine sperm genes. Gene ontology enrichment analyses of three equally sized murine sperm protein groups classified based on their evolutionary rates indicate strongest sperm-specific functional specialization in the most quickly evolving gene class.

CONCLUSIONS: We propose a model according to which slowly evolving murine sperm proteins tend to be constrained by factors such as survival essentiality, network connectivity, and/or broad expression. In contrast, evolutionary change may arise especially in less constrained sperm proteins, which might, moreover, be prone to specialize to reproduction-related functions. Our results should be taken into account in future studies on rate variations of reproductive genes.}, } @article {pmid29580205, year = {2018}, author = {Casjens, SR and Di, L and Akther, S and Mongodin, EF and Luft, BJ and Schutzer, SE and Fraser, CM and Qiu, WG}, title = {Primordial origin and diversification of plasmids in Lyme disease agent bacteria.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {218}, pmid = {29580205}, issn = {1471-2164}, support = {AI07955//National Institute of Allergy and Infectious Diseases/International ; SC1 AI107955/AI/NIAID NIH HHS/United States ; R01 AI049003/AI/NIAID NIH HHS/United States ; R01 GM114817/GM/NIGMS NIH HHS/United States ; G12 MD007599/MD/NIMHD NIH HHS/United States ; MD007599//National Institute on Minority Health and Health Disparities (US)/International ; AI37256//National Institute of Allergy and Infectious Diseases (US)/International ; AI49003//National Institute of Allergy and Infectious Diseases/International ; N01AI30071/AI/NIAID NIH HHS/United States ; AI110820//National Institute of Allergy and Infectious Diseases (US)/International ; GM114817/GM/NIGMS NIH HHS/United States ; }, mesh = {Borrelia burgdorferi/*classification/*genetics/physiology ; Chromosomes, Bacterial ; DNA, Bacterial ; *Genome, Bacterial ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Lyme Disease/*microbiology ; Phylogeny ; Plasmids/genetics ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: With approximately one-third of their genomes consisting of linear and circular plasmids, the Lyme disease agent cluster of species has the most complex genomes among known bacteria. We report here a comparative analysis of plasmids in eleven Borreliella (also known as Borrelia burgdorferi sensu lato) species.

RESULTS: We sequenced the complete genomes of two B. afzelii, two B. garinii, and individual B. spielmanii, B. bissettiae, B. valaisiana and B. finlandensis isolates. These individual isolates carry between seven and sixteen plasmids, and together harbor 99 plasmids. We report here a comparative analysis of these plasmids, along with 70 additional Borreliella plasmids available in the public sequence databases. We identify only one new putative plasmid compatibility type (the 30th) among these 169 plasmid sequences, suggesting that all or nearly all such types have now been discovered. We find that the linear plasmids in the non-B. burgdorferi species have undergone the same kinds of apparently random, chaotic rearrangements mediated by non-homologous recombination that we previously discovered in B. burgdorferi. These rearrangements occurred independently in the different species lineages, and they, along with an expanded chromosomal phylogeny reported here, allow the identification of several whole plasmid transfer events among these species. Phylogenetic analyses of the plasmid partition genes show that a majority of the plasmid compatibility types arose early, most likely before separation of the Lyme agent Borreliella and relapsing fever Borrelia clades, and this, with occasional cross species plasmid transfers, has resulted in few if any species-specific or geographic region-specific Borreliella plasmid types.

CONCLUSIONS: The primordial origin and persistent maintenance of the Borreliella plasmid types support their functional indispensability as well as evolutionary roles in facilitating genome diversity. The improved resolution of Borreliella plasmid phylogeny based on conserved partition-gene clusters will lead to better determination of gene orthology which is essential for prediction of biological function, and it will provide a basis for inferring detailed evolutionary mechanisms of Borreliella genomic variability including homologous gene and plasmid exchanges as well as non-homologous rearrangements.}, } @article {pmid29580201, year = {2018}, author = {Dalongeville, A and Benestan, L and Mouillot, D and Lobreaux, S and Manel, S}, title = {Combining six genome scan methods to detect candidate genes to salinity in the Mediterranean striped red mullet (Mullus surmuletus).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {217}, pmid = {29580201}, issn = {1471-2164}, support = {SEACONNECT//Total/International ; IDEX_0001-02//ANR/International ; }, mesh = {Adaptation, Physiological ; Animals ; Data Interpretation, Statistical ; Genetics, Population ; *Genome ; Genomics/*methods ; *Salinity ; Smegmamorpha/*genetics ; }, abstract = {BACKGROUND: Adaptive genomics may help predicting how a species will respond to future environmental changes. Genomic signatures of local adaptation in marine organisms are often driven by environmental selective agents impacting the physiology of organisms. With one of the highest salinity level, the Mediterranean Sea provides an excellent model to investigate adaptive genomic divergence underlying salinity adaptation. In the present study, we combined six genome scan methods to detect potential genomic signal of selection in the striped red mullet (Mullus surmuletus) populations distributed across a wide salinity gradient. We then blasted these outlier sequences on published fish genomic resources in order to identify relevant potential candidate genes for salinity adaptation in this species.

RESULTS: Altogether, the six genome scan methods found 173 outliers out of 1153 SNPs. Using a blast approach, we discovered four candidate SNPs belonging to three genes potentially implicated in adaptation of M. surmuletus to salinity. The allele frequency at one of these SNPs significantly increases with salinity independently from the effect of longitude. The gene associated to this SNP, SOCS2, encodes for an inhibitor of cytokine and has previously been shown to be expressed under osmotic pressure in other marine organisms. Additionally, our results showed that genome scan methods not correcting for spatial structure can still be an efficient strategy to detect potential footprints of selection, when the spatial and environmental variation are confounded, and then, correcting for spatial structure in a second step represents a conservative method.

CONCLUSION: The present outcomes bring evidences of potential genomic footprint of selection, which suggest an adaptive response of M. surmuletus to salinity conditions in the Mediterranean Sea. Additional genomic data such as sequencing of a full-genome and transcriptome analyses of gene expression would provide new insights regarding the possibility that some striped red mullet populations are locally adapted to their saline environment.}, } @article {pmid29579743, year = {2018}, author = {Palaferri, D and Todorov, Y and Bigioli, A and Mottaghizadeh, A and Gacemi, D and Calabrese, A and Vasanelli, A and Li, L and Davies, AG and Linfield, EH and Kapsalidis, F and Beck, M and Faist, J and Sirtori, C}, title = {Room-temperature nine-µm-wavelength photodetectors and GHz-frequency heterodyne receivers.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {85-88}, pmid = {29579743}, issn = {1476-4687}, abstract = {Room-temperature operation is essential for any optoelectronics technology that aims to provide low-cost, compact systems for widespread applications. A recent technological advance in this direction is bolometric detection for thermal imaging, which has achieved relatively high sensitivity and video rates (about 60 hertz) at room temperature. However, owing to thermally induced dark current, room-temperature operation is still a great challenge for semiconductor photodetectors targeting the wavelength band between 8 and 12 micrometres, and all relevant applications, such as imaging, environmental remote sensing and laser-based free-space communication, have been realized at low temperatures. For these devices, high sensitivity and high speed have never been compatible with high-temperature operation. Here we show that a long-wavelength (nine micrometres) infrared quantum-well photodetector fabricated from a metamaterial made of sub-wavelength metallic resonators exhibits strongly enhanced performance with respect to the state of the art up to room temperature. This occurs because the photonic collection area of each resonator is much larger than its electrical area, thus substantially reducing the dark current of the device. Furthermore, we show that our photonic architecture overcomes intrinsic limitations of the material, such as the drop of the electronic drift velocity with temperature, which constrains conventional geometries at cryogenic operation. Finally, the reduced physical area of the device and its increased responsivity allow us to take advantage of the intrinsic high-frequency response of the quantum detector at room temperature. By mixing the frequencies of two quantum-cascade lasers on the detector, which acts as a heterodyne receiver, we have measured a high-frequency signal, above four gigahertz (GHz). Therefore, these wide-band uncooled detectors could benefit technologies such as high-speed (gigabits per second) multichannel coherent data transfer and high-precision molecular spectroscopy.}, } @article {pmid29579575, year = {2018}, author = {Soyer, JL and Balesdent, MH and Rouxel, T and Dean, RA}, title = {To B or not to B: a tale of unorthodox chromosomes.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {50-57}, doi = {10.1016/j.mib.2018.01.012}, pmid = {29579575}, issn = {1879-0364}, } @article {pmid29579297, year = {2018}, author = {Caspermeyer, J}, title = {Bringing Water to the Fountain of Youth: How New Evidence of Sex Reversals Helps Show How Sex Chromosomes Are Maintained over Evolutionary Time.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {1035-1036}, doi = {10.1093/molbev/msy040}, pmid = {29579297}, issn = {1537-1719}, } @article {pmid29579296, year = {2018}, author = {Caspermeyer, J}, title = {Cockroach Ancient Geographic and Genomic History Traced Back to Last Supercontinent.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {1035}, doi = {10.1093/molbev/msy039}, pmid = {29579296}, issn = {1537-1719}, } @article {pmid29579258, year = {2018}, author = {Willkomm, S and Makarova, KS and Grohmann, D}, title = {DNA silencing by prokaryotic Argonaute proteins adds a new layer of defense against invading nucleic acids.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {376-387}, pmid = {29579258}, issn = {1574-6976}, mesh = {Archaea/genetics/*physiology ; Archaeal Proteins/genetics/*metabolism ; Argonaute Proteins/genetics/*metabolism ; DNA/genetics/metabolism ; Gene Silencing ; }, abstract = {Argonaute (Ago) proteins are encoded in all three domains of life and are responsible for the regulation of intracellular nucleic acid levels. Whereas some Ago variants are able to cleave target nucleic acids by their endonucleolytic activity, others only bind to their target nucleic acids while target cleavage is mediated by other effector proteins. Although all Ago proteins show a high degree of overall structural homology, the nature of the nucleic acid binding partners differs significantly. Recent structural and functional data have provided intriguing new insights into the mechanisms of archaeal and bacterial Ago variants demonstrating the mechanistic diversity within the prokaryotic Ago family with astonishing differences in nucleic acid selection and nuclease specificity. In this review, we provide an overview of the structural organisation of archaeal Ago variants and discuss the current understanding of their biological functions that differ significantly from their eukaryotic counterparts.}, } @article {pmid29579253, year = {2018}, author = {Henry, JJ and Hamilton, PW}, title = {Diverse Evolutionary Origins and Mechanisms of Lens Regeneration.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1563-1575}, pmid = {29579253}, issn = {1537-1719}, abstract = {In this review, we compare and contrast the three different forms of vertebrate lens regeneration: Wolffian lens regeneration, cornea-lens regeneration, and lens regeneration from lens epithelial cells. An examination of the diverse cellular origins of these lenses, their unique phylogenetic distribution, and the underlying molecular mechanisms, suggests that these different forms of lens regeneration evolved independently and utilize neither conserved nor convergent mechanisms to regulate these processes.}, } @article {pmid29579183, year = {2018}, author = {Mori, F and Umezawa, Y and Kondo, R and Wada, M}, title = {Effects of bottom-water hypoxia on sediment bacterial community composition in a seasonally hypoxic enclosed bay (Omura Bay, West Kyushu, Japan).}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy053}, pmid = {29579183}, issn = {1574-6941}, abstract = {The bacterial community strongly drives carbon and other biogeochemical cycles in marine sediment. However, little is known about the impact of dissolved oxygen (DO) availability on bacterial community composition. To fill this gap, we examined diversity, richness and structure of the bacterial population for three consecutive years (2011-2013) in the uppermost (0-5 and 0-7 mm depth) and the subsurface layers (5-10 and 7-14 mm depth) of Omura Bay, Kyushu, Japan, a seasonally hypoxic enclosed bay. Automated ribosomal intergenic spacer analysis revealed a unimodal pattern of diversity indices with DO, peaking at the suboxic (11 μM O2) condition. Shifts in the bacterial communities were also evident in response to the availability of DO. Changes in the operational taxonomic units (OTUs) that were less abundant accounted for a large part of the community dissimilarity. It was further demonstrated that the relative abundance of OTUs affiliated with Gammaproteobacteria was correlated positively with DO, while that with Deltaproteobacteria was inversely correlated with DO. These results strongly suggest that DO availability of bottom water plays a fundamental role in shaping the bacterial community in sediment surfaces of shallow coastal areas.}, } @article {pmid29579182, year = {2018}, author = {Khaliq, I and Hardy, GESJ and White, D and Burgess, TI}, title = {eDNA from roots: a robust tool for determining Phytophthora communities in natural ecosystems.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy048}, pmid = {29579182}, issn = {1574-6941}, abstract = {Proper isolation and identification of Phytophthora species is critical due to their broad distribution and huge impact on natural ecosystems throughout the world. In this study, five different sites were sampled and seven methods were compared to determine the Phytophthora community. Three traditional isolation methods were conducted (i) soil baiting, (ii) filtering of the bait water and (iii) isolation from field roots using Granny Smith apples. These were compared to four sources of eDNA used for metabarcoding using Phytophthora-specific primers on (i) sieved field soil, (ii) roots from field, (iii) filtered baiting water and (iv) roots from bait plants grown in the glasshouse in soil collected from these sites. Six Phytophthora species each were recovered by soil baiting using bait leaves and from the filtered bait water. No Phytophthora species were recovered from Granny Smith apples. eDNA extracted from field roots detected the highest number of Phytophthora species (25). These were followed by direct DNA isolation from filters (24), isolation from roots from bait plants grown in the glasshouse (19), and DNA extraction from field soil (13). Therefore, roots were determined to be the best substrate for detecting Phytophthora communities using eDNA.}, } @article {pmid29579181, year = {2018}, author = {de Menezes, AB and Prendergast-Miller, MT and Macdonald, LM and Toscas, P and Baker, G and Farrell, M and Wark, T and Richardson, AE and Thrall, PH}, title = {Earthworm-induced shifts in microbial diversity in soils with rare versus established invasive earthworm populations.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy051}, pmid = {29579181}, issn = {1574-6941}, abstract = {European earthworms have colonised many parts of Australia, although their impact on soil microbial communities remains largely uncharacterised. An experiment was conducted to contrast the responses to Aporrectodea trapezoides introduction between soils from sites with established (Talmo, 64 A. trapezoides m-2) and rare (Glenrock, 0.6 A. trapezoides m-2) A. trapezoides populations. Our hypothesis was that earthworm introduction would lead to similar changes in bacterial communities in both soils. The effects of earthworm introduction (earthworm activity and cadaver decomposition) did not lead to a convergence of bacterial community composition between the two soils. However, in both soils, the Firmicutes decreased in abundance and a common set of bacteria responded positively to earthworms. The increase in the abundance of Flavobacterium, Chitinophagaceae, Rhodocyclaceae and Sphingobacteriales were consistent with previous studies. Evidence for possible soil resistance to earthworms was observed, with lower earthworm survival in Glenrock microcosms coinciding with A. trapezoides rarity in this site, lower soil organic matter and clay content and differences in the diversity and abundance of potential earthworm mutualist bacteria. These results suggest that while the impacts of earthworms vary between different soils, the consistent response of some bacteria may aid in predicting the impacts of earthworms on soil ecosystems.}, } @article {pmid29578654, year = {2018}, author = {Witteveen, J}, title = {Typological thinking: Then and now.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {3}, pages = {123-131}, pmid = {29578654}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Developmental Biology/*history ; History, 20th Century ; *Models, Biological ; Philosophy/history ; }, abstract = {A popular narrative about the history of modern biology has it that Ernst Mayr introduced the distinction between "typological thinking" and "population thinking" to mark a contrast between a metaphysically problematic and a promising foundation for (evolutionary) biology, respectively. This narrative sometimes continues with the observation that, since the late-20th century, typological concepts have been making a comeback in biology, primarily in the context of evolutionary developmental biology. It is hard to square this narrative with the historical and philosophical literature on the typology/population distinction from the last decade or so. The conclusion that emerges from this literature is that the very distinction between typological thinking and population thinking is a piece of mere rhetoric that was concocted and rehearsed for purely strategic, programmatic reasons. If this is right, it becomes hard to make sense of recent criticisms (and sometimes: espousals) of the purportedly typological underpinnings of certain contemporary research programs. In this article, I offer a way out of this apparent conflict. I show that we can make historical and philosophical sense of the continued accusations of typological thinking by looking beyond Mayr, to his contemporary and colleague George Gaylord Simpson. I show that before Mayr discussed the typology/population distinction as an issue in scientific metaphysics, Simpson introduced it to mark several contrasts in methodology and scientific practice. I argue that Simpson's insightful discussion offers useful resources for classifying and assessing contemporary attributions of typological thinking.}, } @article {pmid29578575, year = {2018}, author = {McQuillan, MA and Roth, TC and Huynh, AV and Rice, AM}, title = {Hybrid chickadees are deficient in learning and memory.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1155-1164}, doi = {10.1111/evo.13470}, pmid = {29578575}, issn = {1558-5646}, abstract = {Identifying the phenotypes underlying postzygotic reproductive isolation is crucial for fully understanding the evolution and maintenance of species. One potential postzygotic isolating barrier that has rarely been examined is learning and memory ability in hybrids. Learning and memory are important fitness-related traits, especially in scatter-hoarding species, where accurate retrieval of hoarded food is vital for winter survival. Here, we test the hypothesis that learning and memory ability can act as a postzygotic isolating barrier by comparing these traits among two scatter-hoarding songbird species, black-capped (Poecile atricapillus) and Carolina chickadees (Poecile carolinensis), and their naturally occurring hybrids. In an outdoor aviary setting, we find that hybrid chickadees perform significantly worse on an associative learning spatial task and are worse at solving a novel problem compared to both parental species. Deficiencies in learning and memory abilities could therefore contribute to postzygotic reproductive isolation between chickadee species. Given the importance of learning and memory for fitness, our results suggest that these traits may play an important, but as yet overlooked, role in postzygotic reproductive isolation.}, } @article {pmid29578318, year = {2018}, author = {Wackett, LP}, title = {Nitrogen gene regulation in environmental microbes: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1296-1297}, doi = {10.1111/1462-2920.14086}, pmid = {29578318}, issn = {1462-2920}, } @article {pmid29578312, year = {2018}, author = {Williams, BAP and Hamilton, KM and Jones, MD and Bass, D}, title = {Group-specific environmental sequencing reveals high levels of ecological heterogeneity across the microsporidian radiation.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {328-336}, doi = {10.1111/1758-2229.12642}, pmid = {29578312}, issn = {1758-2229}, abstract = {The description of diversity is a key imperative in current biological studies and has been revolutionised by the molecular era that allows easy access to microbial diversity not visible to the naked eye. Broadly targeted SSU rRNA gene amplicon studies of diverse environmental habitats continue to reveal new microbial eukaryotic diversity. However, some eukaryotic lineages, particularly parasites, have divergent SSU sequences, and are therefore undersampled or excluded by the methodologies used for SSU studies. One such group is the Microsporidia, which have particularly divergent SSU sequences and are rarely detected in even large-scale amplicon studies. This is a serious omission as microsporidia are diverse and important parasites of humans and other animals of socio-economic importance. Whilst estimates of other microbial diversity are expanding, our knowledge of true microsporidian diversity has remained largely static. In this work, we have combined high throughput sequencing, broad environmental sampling and microsporidian-specific primers to broaden our understanding of the evolutionary diversity of the Microsporidia. Mapping our new sequences onto a tree of known microsporidian diversity we uncover new diversity across all areas of the microsporidian tree and uncover clades dominated by novel sequences, with no close described relatives.}, } @article {pmid29578272, year = {2018}, author = {}, title = {Pleased to edit you: discovering the world of science as a journal editor.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14087}, pmid = {29578272}, issn = {1462-2920}, } @article {pmid29577985, year = {2018}, author = {Nikaido, H}, title = {RND transporters in the living world.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {363-371}, pmid = {29577985}, issn = {1769-7123}, support = {R01 AI009644/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/metabolism ; Bacteria/chemistry/classification/genetics/*metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Eukaryota/chemistry/classification/genetics/*metabolism ; Evolution, Molecular ; Humans ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; Models, Molecular ; *Multigene Family ; }, abstract = {Transporters of the RND superfamily are well-known as the major drug efflux pumps of Gram-negative bacteria. However, they are widespread in organisms ranging from Archaea to Eukaryotes, and perform diverse functions. This review gives a brief overview of these diverse members of the superfamily with emphasis on their structure and functions.}, } @article {pmid29577883, year = {2018}, author = {Parrie, LE and Crowell, JAE and Telling, GC and Bessen, RA}, title = {The cellular prion protein promotes olfactory sensory neuron survival and axon targeting during adult neurogenesis.}, journal = {Developmental biology}, volume = {438}, number = {1}, pages = {23-32}, pmid = {29577883}, issn = {1095-564X}, support = {R21 NS096662/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Axons/metabolism/*physiology ; Blotting, Western ; Cell Differentiation/genetics ; Cell Proliferation/genetics ; Cell Survival/genetics ; Female ; Male ; Mice ; Mice, Transgenic ; Neurogenesis/*genetics/physiology ; Olfactory Receptor Neurons/*metabolism/physiology ; PrPC Proteins/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {The cellular prion protein (PrPC) has been associated with diverse biological processes including cell signaling, neurogenesis, and neuroprotection, but its physiological function(s) remain ambiguous. Here we determine the role of PrPC in adult neurogenesis using the olfactory system model in transgenic mice. Olfactory sensory neurons (OSNs) within the olfactory sensory epithelium (OSE) undergo neurogenesis, integration, and turnover even into adulthood. The neurogenic processes of proliferation, differentiation/maturation, and axon targeting were evaluated in wild type, PrP-overexpressing, and PrP-null transgenic mice. Our results indicate that PrPC plays a role in maintaining mature OSNs within the epithelium: overexpression of PrPC resulted in greater survival of mitotically active cells within the OSE, whereas absence of prion protein resulted in fewer cells being maintained over time. These results are supported by both quantitative PCR analysis of gene expression and protein analysis characteristic of OSN differentiation. Finally, evaluation of axon migration determined that OSN axon targeting in the olfactory bulb is PrPC dose-dependent. Together, these findings provide new mechanistic insight into the neuroprotective role for PrPC in adult OSE neurogenesis, whereby more mature neurons are stably maintained in animals expressing PrPC.}, } @article {pmid29577882, year = {2018}, author = {Kelu, JJ and Webb, SE and Galione, A and Miller, AL}, title = {TPC2-mediated Ca2+ signaling is required for the establishment of synchronized activity in developing zebrafish primary motor neurons.}, journal = {Developmental biology}, volume = {438}, number = {1}, pages = {57-68}, doi = {10.1016/j.ydbio.2018.02.011}, pmid = {29577882}, issn = {1095-564X}, mesh = {Animals ; Animals, Genetically Modified ; Calcium/*metabolism ; Calcium Channels/*metabolism ; Calcium Signaling/*physiology ; Cell Culture Techniques ; Immunohistochemistry ; Motor Neurons/*physiology ; NADP/analogs & derivatives/metabolism ; Zebrafish/metabolism ; Zebrafish Proteins/*metabolism ; }, abstract = {During the development of the early spinal circuitry in zebrafish, spontaneous Ca2+ transients in the primary motor neurons (PMNs) are reported to transform from being slow and uncorrelated, to being rapid, synchronized and patterned. In this study, we demonstrated that in intact zebrafish, Ca2+ release via two-pore channel type 2 (TPC2) from acidic stores/endolysosomes is required for the establishment of synchronized activity in the PMNs. Using the SAIGFF213A;UAS:GCaMP7a double-transgenic zebrafish line, Ca2+ transients were visualized in the caudal PMNs (CaPs). TPC2 inhibition via molecular, genetic or pharmacological means attenuated the CaP Ca2+ transients, and decreased the normal ipsilateral correlation and contralateral anti-correlation, indicating a disruption in normal spinal circuitry maturation. Furthermore, treatment with MS-222 resulted in a complete (but reversible) inhibition of the CaP Ca2+ transients, as well as a significant decrease in the concentration of the Ca2+ mobilizing messenger, nicotinic acid adenine diphosphate (NAADP) in whole embryo extract. Together, our new data suggest a novel function for NAADP/TPC2-mediated Ca2+ signaling in the development, coordination, and maturation of the spinal network in zebrafish embryos.}, } @article {pmid29577670, year = {2018}, author = {}, title = {An autotrophic H2 -oxidizing, nitrate-respiring, Tc(VII)-reducing Acidovorax sp. isolated from a subsurface oxic-anoxic transition zone.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {228}, doi = {10.1111/1758-2229.12636}, pmid = {29577670}, issn = {1758-2229}, } @article {pmid29577669, year = {2018}, author = {Wackett, LP}, title = {Protista: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {226-227}, doi = {10.1111/1758-2229.12643}, pmid = {29577669}, issn = {1758-2229}, mesh = {*Databases, Genetic ; *Environmental Microbiology ; *Eukaryota/classification/genetics/isolation & purification/metabolism ; Internet ; }, } @article {pmid29577506, year = {2018}, author = {Conlon, BH and Frey, E and Rosenkranz, P and Locke, B and Moritz, RFA and Routtu, J}, title = {The role of epistatic interactions underpinning resistance to parasitic Varroa mites in haploid honey bee (Apis mellifera) drones.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {801-809}, doi = {10.1111/jeb.13271}, pmid = {29577506}, issn = {1420-9101}, abstract = {The Red Queen hypothesis predicts that host-parasite coevolutionary dynamics can select for host resistance through increased genetic diversity, recombination and evolutionary rates. However, in haplodiploid organisms such as the honeybee (Apis mellifera), models suggest the selective pressure is weaker than in diploids. Haplodiploid sex determination, found in A. mellifera, can allow deleterious recessive alleles to persist in the population through the diploid sex with negative effects predominantly expressed in the haploid sex. To overcome these negative effects in haploid genomes, epistatic interactions have been hypothesized to play an important role. Here, we use the interaction between A. mellifera and the parasitic mite Varroa destructor to test epistasis in the expression of resistance, through the inhibition of parasite reproduction, in haploid drones. We find novel loci on three chromosomes which explain over 45% of the resistance phenotype. Two of these loci interact only additively, suggesting their expression is independent of each other, but both loci interact epistatically with the third locus. With drone offspring inheriting only one copy of the queen's chromosomes, the drones will only possess one of two queen alleles throughout the years-long lifetime of the honeybee colony. Varroa, in comparison, completes its highly inbred reproductive cycle in a matter of weeks, allowing it to rapidly evolve resistance. Faced with the rapidly evolving Varroa, a diversity of pathways and epistatic interactions for the inhibition of Varroa reproduction could therefore provide a selective advantage to the high levels of recombination seen in A. mellifera. This allows for the remixing of phenotypes despite a fixed queen genotype.}, } @article {pmid29577502, year = {2018}, author = {Maronde, L and Losdat, S and Richner, H}, title = {Do parasites and antioxidant availability affect begging behaviour, growth rate and resistance to oxidative stress?.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {904-913}, doi = {10.1111/jeb.13274}, pmid = {29577502}, issn = {1420-9101}, abstract = {Early-life trade-offs faced by developing offspring can have long-term consequences for their future fitness. Young offspring use begging displays to solicit resources from their parents and have been selected to grow fast to maximize survival. However, growth and begging behaviour are generally traded off against self-maintenance. Oxidative stress, a physiological mediator of life-history trade-offs, may play a major role in this trade-off by constraining, or being costly to, growth and begging behaviour. Yet, despite implications for the evolution of life-history strategies and parent-offspring conflicts, the interplay between growth, begging behaviour and resistance to oxidative stress remains to be investigated. We experimentally challenged wild great tit (Parus major) offspring by infesting nests with a common ectoparasite, the hen flea (Ceratophyllus gallinae), and simultaneously tested for compensating effects of increased vitamin E availability, a common dietary antioxidant. We further quantified the experimental treatment effects on offspring growth, begging intensity and oxidative stress. Flea-infested nestlings of both sexes showed reduced body mass during the first half of the nestling phase, but this effect vanished short before fledging. Begging intensity and oxidative stress of both sexes were unaffected by both experimental treatments. Feeding rates were not affected by the experimental treatments, but parents of flea-infested nests fed nestlings with a higher proportion of caterpillars, the main source of antioxidants. Additionally, female nestlings begged significantly less than males in control nests, whereas both sexes begged at similar rates in vitamin E-supplemented nests. Our study shows that a parasite exposure does not necessarily affect oxidative stress levels or begging intensity, but suggests that parents can compensate for negative effects of parasitism by modifying food composition. Furthermore, our results indicate that the begging capacity of the less competitive sex is constrained by antioxidant availability.}, } @article {pmid29577500, year = {2018}, author = {Olave, M and Avila, LJ and Sites, JW and Morando, M}, title = {Hybridization could be a common phenomenon within the highly diverse lizard genus Liolaemus.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {893-903}, doi = {10.1111/jeb.13273}, pmid = {29577500}, issn = {1420-9101}, abstract = {Hybridization is likely to occur more often between closely related taxa that have had insufficient time to diverge to the point of reproductive incompatibility; hybridization between deeply divergent lineages is rare. In squamate reptiles, hybridization has been proposed as a possible explanation for the extensive paraphyly observed in mitochondrial gene trees in several species complexes of the South American lizard genus Liolaemus. One of the best-documented cases is within the L. boulengeri and L. rothi complexes, which diverged ~5.5 million years ago. Here, we describe a comprehensive study for approaching the hybridization hypothesis between these lizard species complexes. We explored the level of gene tree discordance using the novel 'extra lineage contribution' statistics (XLC, presented in this study) that quantifies the level of gene tree discordance contribution per individual within a species. We included molecular data (12 nuclear and two mitochondrial genes) from 127 individuals, and results of a coalescent model-based analysis show that the most likely explanation for the gene tree-species tree discordance is interspecific hybridization. Our best-supported hypothesis suggests current and past hybridization between L. rothi (rothi complex) and L. tehuelche (boulengeri complex), and independently between L. rothi and L. boulengeri and L. telsen (boulengeri complex). The hybrid descendants are characterized by intermediate phenotypes between the parental species, but are more similar to L. rothi in body size. We discuss the possible role of hybridization in Liolaemus evolution.}, } @article {pmid29577482, year = {2018}, author = {Pires, THS and Borghezan, EA and Machado, VN and Powell, DL and Röpke, CP and Oliveira, C and Zuanon, J and Farias, IP}, title = {Testing Wallace's intuition: water type, reproductive isolation and divergence in an Amazonian fish.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {882-892}, doi = {10.1111/jeb.13272}, pmid = {29577482}, issn = {1420-9101}, abstract = {Alfred Russel Wallace proposed classifying Amazon rivers based on their colour and clarity: white, black and clear water. Wallace also proposed that black waters could mediate diversification and yield distinct fish species. Here, we bring evidence of speciation mediated by water type in the sailfin tetra (Crenuchus spilurus), a fish whose range encompasses rivers of very distinct hydrochemical conditions. Distribution of the two main lineages concords with Wallace's water types: one restricted to the acidic and nutrient-poor waters of the Negro River (herein Rio Negro lineage) and a second widespread throughout the remaining of the species' distribution (herein Amazonas lineage). These lineages occur over a very broad geographical range, suggesting that despite occurring in regions separated by thousands of kilometres, individuals of the distinct lineages fail to occupy each other's habitats, hundreds of metres apart and not separated by physical barrier. Reproductive isolation was assessed in isolated pairs exposed to black-water conditions. All pairs with at least one individual of the lineage not native to black waters showed significantly lower spawning success, suggesting that the water type affected the fitness and contributed to reproductive isolation. Our results endorse Wallace's intuition and highlight the importance of ecological factors in shaping diversity of the Amazon fish fauna.}, } @article {pmid29576862, year = {2018}, author = {Stabler, D and Power, EF and Borland, AM and Barnes, JD and Wright, GA}, title = {A method for analysing small samples of floral pollen for free and protein-bound amino acids.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {2}, pages = {430-438}, pmid = {29576862}, issn = {2041-210X}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Pollen provides floral visitors with essential nutrients including proteins, lipids, vitamins and minerals. As an important nutrient resource for pollinators, including honeybees and bumblebees, pollen quality is of growing interest in assessing available nutrition to foraging bees. To date, quantifying the protein-bound amino acids in pollen has been difficult and methods rely on large amounts of pollen, typically more than 1 g. More usual is to estimate a crude protein value based on the nitrogen content of pollen, however, such methods provide no information on the distribution of essential and non-essential amino acids constituting the proteins.Here, we describe a method of microwave-assisted acid hydrolysis using low amounts of pollen that allows exploration of amino acid composition, quantified using ultra high performance liquid chromatography (UHPLC), and a back calculation to estimate the crude protein content of pollen.Reliable analysis of protein-bound and free amino acids as well as an estimation of crude protein concentration was obtained from pollen samples as low as 1 mg. Greater variation in both protein-bound and free amino acids was found in pollen sample sizes <1 mg. Due to the variability in recovery of amino acids in smaller sample sizes, we suggest a correction factor to apply to specific sample sizes of pollen in order to estimate total crude protein content.The method described in this paper will allow researchers to explore the composition of amino acids in pollen and will aid research assessing the available nutrition to pollinating animals. This method will be particularly useful in assaying the pollen of wild plants, from which it is difficult to obtain large sample weights.}, } @article {pmid29576620, year = {2018}, author = {Du Toit, A}, title = {Marine microbiology: Carbon export into the deep ocean.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {260-261}, doi = {10.1038/nrmicro.2018.37}, pmid = {29576620}, issn = {1740-1534}, } @article {pmid29576619, year = {2018}, author = {Lo, SW and Kumar, N and Wheeler, NE}, title = {Breaking the code of antibiotic resistance.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {262}, pmid = {29576619}, issn = {1740-1534}, } @article {pmid29576616, year = {2018}, author = {Hens, K and Noens, I and Peeters, H and Steyaert, J}, title = {The ethics of patenting autism genes.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {247-248}, pmid = {29576616}, issn = {1471-0064}, } @article {pmid29576615, year = {2018}, author = {Salk, JJ and Schmitt, MW and Loeb, LA}, title = {Enhancing the accuracy of next-generation sequencing for detecting rare and subclonal mutations.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {269-285}, pmid = {29576615}, issn = {1471-0064}, support = {P01 CA077852/CA/NCI NIH HHS/United States ; R01 CA193649/CA/NCI NIH HHS/United States ; R33 CA181771/CA/NCI NIH HHS/United States ; T32 CA009515/CA/NCI NIH HHS/United States ; }, abstract = {Mutations, the fuel of evolution, are first manifested as rare DNA changes within a population of cells. Although next-generation sequencing (NGS) technologies have revolutionized the study of genomic variation between species and individual organisms, most have limited ability to accurately detect and quantify rare variants among the different genome copies in heterogeneous mixtures of cells or molecules. We describe the technical challenges in characterizing subclonal variants using conventional NGS protocols and the recent development of error correction strategies, both computational and experimental, including consensus sequencing of single DNA molecules. We also highlight major applications for low-frequency mutation detection in science and medicine, describe emerging methodologies and provide our vision for the future of DNA sequencing.}, } @article {pmid29576614, year = {2018}, author = {Otto, G}, title = {Human genetics: Population-scale family trees from publicly available data.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {250-251}, pmid = {29576614}, issn = {1471-0064}, } @article {pmid29576018, year = {2018}, author = {Sasson, DA and Jacquez, AA and Ryan, JF}, title = {The ctenophore Mnemiopsis leidyi regulates egg production via conspecific communication.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {12}, pmid = {29576018}, issn = {1472-6785}, support = {1542597//National Science Foundation/International ; }, abstract = {BACKGROUND: Communication between individuals of the same species is an important aspect of mating and reproduction in most animals. In simultaneously hermaphroditic species with the ability to self-fertilize, communication with conspecifics can be essential to avoid inbreeding depression. One such behavioral adaptation observed in some simultaneous hermaphrodites is gamete trading. This behavior involves individual hermaphrodites in pairs alternating between reproducing as the male and female, and, as such, necessarily requires communication and coordination between mates. Little is known about communication in ctenophores and conspecific communication has not been described in this group; however, our previous work suggested that the ctenophore Mnemiopsis leidyi might engage in gamete trading. We tested for this possibility by constructing divided arenas (both sealed and permeable) that allowed us to measure individual egg output for paired M. leidyi.

RESULTS: We found that, when not allowed to interact, size-matched individuals produced similar numbers of eggs on each side of the arena. However, if allowed to interact and exchange water, size-matched pairs produce significantly different numbers of eggs on each side of the arena, suggesting that these pairs use chemical communication to modulate reproduction in the presence of conspecifics as would be expected in gamete trading.

CONCLUSION: This finding presents exciting new possibilities for future investigations into the nature of signaling in M. leidyi. Furthermore, this first evidence of conspecific communication in Ctenophora, a group that branched off from the rest of animals more than 600 million years ago, has significant implications for the signaling ability of the last common ancestor of all animals.}, } @article {pmid29575704, year = {2018}, author = {Cai, Q and Wang, ZK and Shao, W and Ying, SH and Feng, MG}, title = {Essential role of Rpd3-dependent lysine modification in the growth, development and virulence of Beauveria bassiana.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1590-1606}, doi = {10.1111/1462-2920.14100}, pmid = {29575704}, issn = {1462-2920}, abstract = {Rpd3 is a class I histone deacetylase that reverses lysine acetylation thus influencing cellular processes and functions. However, its role in fungal insect pathogens has not been explored yet. Here we show that Rpd3-dependent lysine modification and gene expression orchestrate growth, conidiation and virulence in Beauveria bassiana. Deletion of Rpd3 resulted in severe growth defects on various carbon/nitrogen sources, 97% reduction in conidiation capacity and drastic attenuation in virulence. These phenotypes concurred with differential expression of 1479 proteins and hyperacetylation or hypoacetylation of 2227 lysine residues on 1134 proteins. Many of these proteins fell into carbon/nitrogen metabolism and cell rescue/defence/virulence, indicating vital roles of Rpd3-dependent protein expression and lysine modification in the fungal growth and virulence. Intriguingly, lysine residues of four core histones (H2A, H2B, H3 and H4) and many histone acetyltransferases were also hyper- or hypoacetylated in Δrpd3, suggesting direct and indirect roles for Rpd3 in genome-wide lysine modification. However, crucial development activators were transcriptionally repressed and not found in either proteome or acetylome. Single/double-site-directed H3K9/K14 mutations for hyper/hypoacetylation exerted significant impacts on conidiation and dimorphic transition crucial for fungal virulence. Altogether, Rpd3 mediates growth, asexual development and virulence through transcriptional/translational regulation and posttranslational lysine modification in B. bassiana.}, } @article {pmid29575680, year = {2018}, author = {Agha, M and Ennen, JR and Bower, DS and Nowakowski, AJ and Sweat, SC and Todd, BD}, title = {Salinity tolerances and use of saline environments by freshwater turtles: implications of sea level rise.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1634-1648}, doi = {10.1111/brv.12410}, pmid = {29575680}, issn = {1469-185X}, abstract = {The projected rise in global mean sea levels places many freshwater turtle species at risk of saltwater intrusion into freshwater habitats. Freshwater turtles are disproportionately more threatened than other taxa; thus, understanding the role of salinity in determining their contemporary distribution and evolution should be a research priority. Freshwater turtles are a slowly evolving lineage; however, they can adapt physiologically or behaviourally to various levels of salinity and, therefore, temporarily occur in marine or brackish environments. Here, we provide the first comprehensive global review on freshwater turtle use and tolerance of brackish water ecosystems. We link together current knowledge of geographic occurrence, salinity tolerance, phylogenetic relationships, and physiological and behavioural mechanisms to generate a baseline understanding of the response of freshwater turtles to changing saline environments. We also review the potential origins of salinity tolerance in freshwater turtles. Finally, we integrate 2100 sea level rise (SLR) projections, species distribution maps, literature gathered on brackish water use, and a phylogeny to predict the exposure of freshwater turtles to projected SLR globally. From our synthesis of published literature and available data, we build a framework for spatial and phylogenetic conservation prioritization of coastal freshwater turtles. Based on our literature review, 70 species (∼30% of coastal freshwater turtle species) from 10 of the 11 freshwater turtle families have been reported in brackish water ecosystems. Most anecdotal records, observations, and descriptions do not imply long-term salinity tolerance among freshwater turtles. Rather, experiments show that some species exhibit potential for adaptation and plasticity in physiological, behavioural, and life-history traits that enable them to endure varying periods (e.g. days or months) and levels of saltwater exposure. Species that specialize on brackish water habitats are likely to be vulnerable to SLR because of their exclusive coastal distributions and adaptations to a narrow range of salinities. Most species, however, have not been documented in brackish water habitats but may also be highly vulnerable to projected SLR. Our analysis suggests that approximately 90% of coastal freshwater turtle species assessed in our study will be affected by a 1-m increase in global mean SLR by 2100. Most at risk are freshwater turtles found in New Guinea, Southeast Asia, Australia, and North and South America that may lose more than 10% of their present geographic range. In addition, turtle species in the families Chelidae, Emydidae, and Trionychidae may experience the greatest exposure to projected SLR in their present geographic ranges. Better understanding of survival, growth, reproductive and population-level responses to SLR will improve region-specific population viability predictions of freshwater turtles that are increasingly exposed to SLR. Integrating phylogenetic, physiological, and spatial frameworks to assess the effects of projected SLR may improve identification of vulnerable species, guilds, and geographic regions in need of conservation prioritization. We conclude that the use of brackish and marine environments by freshwater turtles provides clues about the evolutionary processes that have prolonged their existence, shaped their unique coastal distributions, and may prove useful in predicting their response to a changing world.}, } @article {pmid29575679, year = {2018}, author = {Zhou, Y and Zhu, H and Yao, Q}, title = {Contrasting P acquisition strategies of the bacterial communities associated with legume and grass in subtropical orchard soil.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {310-319}, doi = {10.1111/1758-2229.12641}, pmid = {29575679}, issn = {1758-2229}, abstract = {Phosphorus (P) cycling is a fundamental process driven by microorganisms, and plants can regulate P cycling directly or via their influence on the soil microbial community. However, the differential P cycling patterns associated with legumes and grass are largely unknown. Therefore, we investigated the microbial community involved in P cycling in subtropical soil grown with stylo (Stylosanthes guianensis, legume) or bahiagrass (Paspalum notatum, grass) using metagenomic sequencing. P fractionation indicated that sparingly soluble inorganic P (Pi) accounted for approximately 75% of P pool. Bacteria involved in sparingly soluble Pi solubilization (pqq, gad, JEN) were more abundant in bahiagrass soil, with Candidatus Pelagibacter, Trichodesmium, Neorickettsia, Nitrobacter, Paraburkholderia, Candidatus Solibacter, Burkholderia as major contributors. In contrast, bacteria involved in organic P (Po) mineralization (php, glpQ, phn) were more abundant in stylo soil, consistent with phosphatase activity and Frankia, Kyrpidia, Thermobispora, Streptomyces, Rhodococcus were major contributors. Bacteria taking up low molecular-weight Po were more abundant in stylo soil than in bahiagrass soil, while those taking up Pi were less abundant. These data suggest that bacterial communities associated with legumes and grass develop contrasting P acquisition strategies, highlighting the possibility of intercropping with legumes and grass for better P cycling.}, } @article {pmid29575574, year = {2018}, author = {Kell, DB and Pretorius, E}, title = {No effects without causes: the Iron Dysregulation and Dormant Microbes hypothesis for chronic, inflammatory diseases.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1518-1557}, pmid = {29575574}, issn = {1469-185X}, support = {BB/L025752/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Since the successful conquest of many acute, communicable (infectious) diseases through the use of vaccines and antibiotics, the currently most prevalent diseases are chronic and progressive in nature, and are all accompanied by inflammation. These diseases include neurodegenerative (e.g. Alzheimer's, Parkinson's), vascular (e.g. atherosclerosis, pre-eclampsia, type 2 diabetes) and autoimmune (e.g. rheumatoid arthritis and multiple sclerosis) diseases that may appear to have little in common. In fact they all share significant features, in particular chronic inflammation and its attendant inflammatory cytokines. Such effects do not happen without underlying and initially 'external' causes, and it is of interest to seek these causes. Taking a systems approach, we argue that these causes include (i) stress-induced iron dysregulation, and (ii) its ability to awaken dormant, non-replicating microbes with which the host has become infected. Other external causes may be dietary. Such microbes are capable of shedding small, but functionally significant amounts of highly inflammagenic molecules such as lipopolysaccharide and lipoteichoic acid. Sequelae include significant coagulopathies, not least the recently discovered amyloidogenic clotting of blood, leading to cell death and the release of further inflammagens. The extensive evidence discussed here implies, as was found with ulcers, that almost all chronic, infectious diseases do in fact harbour a microbial component. What differs is simply the microbes and the anatomical location from and at which they exert damage. This analysis offers novel avenues for diagnosis and treatment.}, } @article {pmid29575552, year = {2018}, author = {Laffy, PW and Wood-Charlson, EM and Turaev, D and Jutz, S and Pascelli, C and Botté, ES and Bell, SC and Peirce, TE and Weynberg, KD and van Oppen, MJH and Rattei, T and Webster, NS}, title = {Reef invertebrate viromics: diversity, host specificity and functional capacity.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14110}, pmid = {29575552}, issn = {1462-2920}, abstract = {Recent metagenomic analyses have revealed a high diversity of viruses in the pelagic ocean and uncovered clear habitat-specific viral distribution patterns. Conversely, similar insights into the composition, host specificity and function of viruses associated with marine organisms have been limited by challenges associated with sampling and computational analysis. Here, we performed targeted viromic analysis of six coral reef invertebrate species and their surrounding seawater to deliver taxonomic and functional profiles of viruses associated with reef organisms. Sponges and corals' host species-specific viral assemblages with low sequence identity to known viral genomes. While core viral genes involved in capsid formation, tail structure and infection mechanisms were observed across all reef samples, auxiliary genes including those involved in herbicide resistance and viral pathogenesis pathways such as host immune suppression were differentially enriched in reef hosts. Utilising a novel OTU based assessment, we also show a prevalence of dsDNA viruses belonging to the Mimiviridae, Caudovirales and Phycodnaviridae in reef environments and further highlight the abundance of ssDNA viruses belonging to the Circoviridae, Parvoviridae, Bidnaviridae and Microviridae in reef invertebrates. These insights into coral reef viruses provide an important framework for future research into how viruses contribute to the health and evolution of reef organisms.}, } @article {pmid29575531, year = {2018}, author = {Plominsky, AM and Trefault, N and Podell, S and Blanton, JM and De la Iglesia, R and Allen, EE and von Dassow, P and Ulloa, O}, title = {Metabolic potential and in situ transcriptomic profiles of previously uncharacterized key microbial groups involved in coupled carbon, nitrogen and sulfur cycling in anoxic marine zones.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2727-2742}, doi = {10.1111/1462-2920.14109}, pmid = {29575531}, issn = {1462-2920}, support = {IC 120019//Millennium Science Initiative/ ; Fondecyt 1161483//Chilean National Commision for Scientific and Technological Research/ ; Conicyt-USA 20120014//Chilean National Commision for Scientific and Technological Research/ ; 3140191//Chilean National Commision for Scientific and Technological Research/ ; DGE-1144086//US National Science Foundation/ ; MCB-1149552//US National Science Foundation/ ; }, abstract = {Anoxic marine zones (AMZs) impact biogeochemical cycles at the global scale, particularly the nitrogen cycle. Key microbial players from AMZs have been identified, but the majority remains unrecognized or uncharacterized. Thirty-one single-cell amplified genomes (SAGs) from the eastern tropical North and South Pacific AMZs were sequenced to gain insight into the distribution, metabolic potential and contribution to the community transcriptional profile of these uncharacterized bacterial and archaeal groups. Detailed analyses focused on SAG-bins assigned to three of these groups that presented 79%-100% estimated genome completeness: the putative sulphur-oxidizing Gamaproteobacteria EOSA II clade, a Marinimicrobia member of the recently recognized PN262000N21 clade found to be abundant in AMZ anoxic cores, and a representative of the Marine Benthic Group A Thaumarchaeota. Community-based analyses revealed that these three groups are significantly more abundant and transcriptionally more active in the AMZ microbial communities than previously described phylogenetically related microbial groups. Collectively, these groups have the potential to link biogeochemically relevant processes by coupling the carbon, nitrogen and sulfur cycles. Together, these results increase our understanding of key microbial components inhabiting AMZs and other oxygen-deficient marine environments, enhancing our capacity to predict the impact of the expansion of these ecosystems due to climate change.}, } @article {pmid29575522, year = {2018}, author = {Wang, Q and Kang, YS and Alowaifeer, A and Shi, K and Fan, X and Wang, L and Jetter, J and Bothner, B and Wang, G and McDermott, TR}, title = {Phosphate starvation response controls genes required to synthesize the phosphate analog arsenate.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1782-1793}, doi = {10.1111/1462-2920.14108}, pmid = {29575522}, issn = {1462-2920}, abstract = {Environmental arsenic poisoning affects roughly 200 million people worldwide. The toxicity and mobility of arsenic in the environment is significantly influenced by microbial redox reactions, with arsenite (AsIII) being more toxic than arsenate (AsV). Microbial oxidation of AsIII to AsV is known to be regulated by the AioXSR signal transduction system and viewed to function for detoxification or energy generation. Here, we show that AsIII oxidation is ultimately regulated by the phosphate starvation response (PSR), requiring the sensor kinase PhoR for expression of the AsIII oxidase structural genes aioBA. The PhoRB and AioSR signal transduction systems are capable of transphosphorylation cross-talk, closely integrating AsIII oxidation with the PSR. Further, under PSR conditions, AsV significantly extends bacterial growth and accumulates in the lipid fraction to the apparent exclusion of phosphorus. This could spare phosphorus for nucleic acid synthesis or triphosphate metabolism wherein unstable arsenic esters are not tolerated, thereby enhancing cell survival potential. We conclude that AsIII oxidation is logically part of the bacterial PSR, enabling the synthesis of the phosphate analog AsV to replace phosphorus in specific biomolecules or to synthesize other molecules capable of a similar function, although not for total replacement of cellular phosphate.}, } @article {pmid29575513, year = {2018}, author = {Martín-Hernández, R and Bartolomé, C and Chejanovsky, N and Le Conte, Y and Dalmon, A and Dussaubat, C and García-Palencia, P and Meana, A and Pinto, MA and Soroker, V and Higes, M}, title = {Nosema ceranae in Apis mellifera: a 12 years postdetection perspective.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1302-1329}, doi = {10.1111/1462-2920.14103}, pmid = {29575513}, issn = {1462-2920}, abstract = {Nosema ceranae is a hot topic in honey bee health as reflected by numerous papers published every year. This review presents an update of the knowledge generated in the last 12 years in the field of N. ceranae research, addressing the routes of transmission, population structure and genetic diversity. This includes description of how the infection modifies the honey bee's metabolism, the immune response and other vital functions. The effects on individual honey bees will have a direct impact on the colony by leading to losses in the adult's population. The absence of clear clinical signs could keep the infection unnoticed by the beekeeper for long periods. The influence of the environmental conditions, beekeeping practices, bee genetics and the interaction with pesticides and other pathogens will have a direct influence on the prognosis of the disease. This review is approached from the point of view of the Mediterranean countries where the professional beekeeping has a high representation and where this pathogen is reported as an important threat.}, } @article {pmid29575500, year = {2018}, author = {Huggett, MJ and McMahon, K and Bernasconi, R}, title = {Future warming and acidification result in multiple ecological impacts to a temperate coralline alga.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2769-2782}, doi = {10.1111/1462-2920.14113}, pmid = {29575500}, issn = {1462-2920}, support = {//Nectar Research Cloud/ ; //National Collaborative Research Infrastructure Strategy (NCRIS)/ ; }, abstract = {Coralline algae are a crucial component of reef systems, stabilising reef substrate, providing habitat and contributing to accretion. Coralline algae and their surface microbial biofilms are also important as settlement cues for marine invertebrates, yet few studies address the impact of future environmental conditions on interactions between coralline algae, reef microbes and settlement by larvae of marine invertebrates. We exposed the temperate coralline algal species Amphiroa gracilis to warming and/or acidification scenarios for 21 days. Algae became bleached but photosystem II function was not measurably impacted. Settlement by larvae of the sea urchin Heliocidaris erythrogramma was reduced and the structure of the prokaryotic community associated with A. gracilis was altered. Coralline algae in ambient conditions were dominated by Alphaproteobacteria from the Rhodobacteraceae including Loktonella; those under warming were dominated by Bacteroidetes and Verrucomicrobia; acidification resulted in less Loktonella and more Planctomycetes and a combination of warming and acidification caused increases in Bacteroidetes, Verrucomicrobia and the Alphaproteobacteria family Hyphomonadaceae. These experiments indicate that predicted future environmental change may reduce the ability of some temperate reef coralline algae and associated reef microbes to facilitate settlement of invertebrate larvae as well as having a direct impact to algae via bleaching.}, } @article {pmid29575486, year = {2018}, author = {Feng, Z and Tian, J and Han, L and Geng, Y and Sun, J and Kong, Z}, title = {The Myosin5-mediated actomyosin motility system is required for Verticillium pathogenesis of cotton.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1607-1621}, doi = {10.1111/1462-2920.14101}, pmid = {29575486}, issn = {1462-2920}, abstract = {The vascular wilt fungus Verticillium dahliae is one of the most destructive pathogens of cotton (Gossypium hirsutum) and many other economically important dicot plants. Fungal pathogens require Myosin-mediated actomyosin motility system for colonization of their host plants; however, the mechanisms underlying this process have not been fully characterized for V. dahliae. Here, in a knock-out experiment, we characterized the role of VdMyo5, a member of the Myosin V family, before and during infection of cotton and Arabidopsis thaliana. The VdMyo5 deletion mutant (ΔVdmyo5) fungi showed obvious defects in the development of conidia and the polarized elongation of vegetative hyphae, but no inhibition of host root penetration. Overall, the ΔVdmyo5 fungi exhibited dramatically reduced virulence in cotton and Arabidopsis, with almost no colonization in sections of host vascular tissue. We found labelled Myosin5-GFP to be specifically enriched at the hyphal tip, co-localized with FM4-64 labelled Spitzenkörper, which is the vesicle supply centre in filamentous fungi. Comparative secretome analysis revealed that proteins associated with cell wall modification and degradation of reactive oxygen species were significantly altered in mutant strains. Our results indicate that Myosin5 is required for vegetative growth and full virulence, possibly by regulating vesicle transport. The findings provide important insight into the cellular mechanisms of Verticillium pathogenesis.}, } @article {pmid29575463, year = {2018}, author = {de Lorenzo, V}, title = {Environmental microbiology to the rescue of planet earth.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14105}, pmid = {29575463}, issn = {1462-2920}, abstract = {Environmental Microbiology has undergone a dramatic transition from being a somewhat marginal branch of Life Sciences to becoming one of the most vibrant and visible areas of contemporary research. The homonymous journal has not only borne witness of the growing interest in environmental microbes that bloomed since the mid-1980s but it has helped also to give visibility to the field and nucleate an active and influential community of authors and readers. During the past 20 years the focus has shifted from individual isolates to communities and microbiomes, from single genomes to metagenomes and from small/medium-scale experimental systems to large/very large scenarios. New challenges that were somewhat marginal when the journal was founded have acquired an unanticipated relevance owing to their impact on the global Earth's homeostasis. They include the unacceptably high atmospheric levels of greenhouse gases, the worrying pollution of the oceans with very recalcitrant plastics and microplastics and the noxious effects of micropollutants on many ecosystems. Global problems ask for global solutions and the environmental microbiome - because of its dimension and its amazing activities - may end up being out best instrument to both counter the impact of industrial development and enable a new, sustainable partnership with Nature.}, } @article {pmid29575449, year = {2018}, author = {Reid, JM and Travis, JMJ and Daunt, F and Burthe, SJ and Wanless, S and Dytham, C}, title = {Population and evolutionary dynamics in spatially structured seasonally varying environments.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1578-1603}, doi = {10.1111/brv.12409}, pmid = {29575449}, issn = {1469-185X}, abstract = {Increasingly imperative objectives in ecology are to understand and forecast population dynamic and evolutionary responses to seasonal environmental variation and change. Such population and evolutionary dynamics result from immediate and lagged responses of all key life-history traits, and resulting demographic rates that affect population growth rate, to seasonal environmental conditions and population density. However, existing population dynamic and eco-evolutionary theory and models have not yet fully encompassed within-individual and among-individual variation, covariation, structure and heterogeneity, and ongoing evolution, in a critical life-history trait that allows individuals to respond to seasonal environmental conditions: seasonal migration. Meanwhile, empirical studies aided by new animal-tracking technologies are increasingly demonstrating substantial within-population variation in the occurrence and form of migration versus year-round residence, generating diverse forms of 'partial migration' spanning diverse species, habitats and spatial scales. Such partially migratory systems form a continuum between the extreme scenarios of full migration and full year-round residence, and are commonplace in nature. Here, we first review basic scenarios of partial migration and associated models designed to identify conditions that facilitate the maintenance of migratory polymorphism. We highlight that such models have been fundamental to the development of partial migration theory, but are spatially and demographically simplistic compared to the rich bodies of population dynamic theory and models that consider spatially structured populations with dispersal but no migration, or consider populations experiencing strong seasonality and full obligate migration. Second, to provide an overarching conceptual framework for spatio-temporal population dynamics, we define a 'partially migratory meta-population' system as a spatially structured set of locations that can be occupied by different sets of resident and migrant individuals in different seasons, and where locations that can support reproduction can also be linked by dispersal. We outline key forms of within-individual and among-individual variation and structure in migration that could arise within such systems and interact with variation in individual survival, reproduction and dispersal to create complex population dynamics and evolutionary responses across locations, seasons, years and generations. Third, we review approaches by which population dynamic and eco-evolutionary models could be developed to test hypotheses regarding the dynamics and persistence of partially migratory meta-populations given diverse forms of seasonal environmental variation and change, and to forecast system-specific dynamics. To demonstrate one such approach, we use an evolutionary individual-based model to illustrate that multiple forms of partial migration can readily co-exist in a simple spatially structured landscape. Finally, we summarise recent empirical studies that demonstrate key components of demographic structure in partial migration, and demonstrate diverse associations with reproduction and survival. We thereby identify key theoretical and empirical knowledge gaps that remain, and consider multiple complementary approaches by which these gaps can be filled in order to elucidate population dynamic and eco-evolutionary responses to spatio-temporal seasonal environmental variation and change.}, } @article {pmid29575448, year = {2018}, author = {Tsementzi, D and Castro Gordillo, J and Mahagna, M and Gottlieb, Y and Konstantinidis, KT}, title = {Comparison of closely related, uncultivated Coxiella tick endosymbiont population genomes reveals clues about the mechanisms of symbiosis.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1751-1764}, doi = {10.1111/1462-2920.14104}, pmid = {29575448}, issn = {1462-2920}, abstract = {Understanding the symbiotic interaction between Coxiella-like endosymbionts (CLE) and their tick hosts is challenging due to lack of isolates and difficulties in tick functional assays. Here we sequenced the metagenome of a CLE population from wild Rhipicephalus sanguineus ticks (CRs) and compared it to the previously published genome of its close relative, CLE of R. turanicus (CRt). The tick hosts are closely related sympatric species, and their two endosymbiont genomes are highly similar with only minor differences in gene content. Both genomes encode numerous pseudogenes, consistent with an ongoing genome reduction process. In silico flux balance metabolic analysis (FBA) revealed the excess production of L-proline for both genomes, indicating a possible proline transport from Coxiella to the tick. Additionally, both CR genomes encode multiple copies of the proline/betaine transporter, proP gene. Modelling additional Coxiellaceae members including other tick CLE, did not identify proline as an excreted metabolite. Although both CRs and CRt genomes encode intact B vitamin synthesis pathway genes, which are presumed to underlay the mechanism of CLE-tick symbiosis, the FBA analysis indicated no changes for their products. Therefore, this study provides new testable hypotheses for the symbiosis mechanism and a better understanding of CLE genome evolution and diversity.}, } @article {pmid29575407, year = {2018}, author = {Radzvilavicius, AL and Blackstone, NW}, title = {The evolution of individuality revisited.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1620-1633}, doi = {10.1111/brv.12412}, pmid = {29575407}, issn = {1469-185X}, abstract = {Evolutionary theory is formulated in terms of individuals that carry heritable information and are subject to selective pressures. However, individuality itself is a trait that had to evolve - an individual is not an indivisible entity, but a result of evolutionary processes that necessarily begin at the lower level of hierarchical organisation. Traditional approaches to biological individuality focus on cooperation and relatedness within a group, division of labour, policing mechanisms and strong selection at the higher level. Nevertheless, despite considerable theoretical progress in these areas, a full dynamical first-principles account of how new types of individuals arise is missing. To the extent that individuality is an emergent trait, the problem can be approached by recognising the importance of individuating mechanisms that are present from the very beginning of the transition, when only lower-level selection is acting. Here we review some of the most influential theoretical work on the role of individuating mechanisms in these transitions, and demonstrate how a lower-level, bottom-up evolutionary framework can be used to understand biological complexity involved in the origin of cellular life, early eukaryotic evolution, sexual life cycles and multicellular development. Some of these mechanisms inevitably stem from environmental constraints, population structure and ancestral life cycles. Others are unique to specific transitions - features of the natural history and biochemistry that are co-opted into conflict mediation. Identifying mechanisms of individuation that provide a coarse-grained description of the system's evolutionary dynamics is an important step towards understanding how biological complexity and hierarchical organisation evolves. In this way, individuality can be reconceptualised as an approximate model that with varying degrees of precision applies to a wide range of biological systems.}, } @article {pmid29575403, year = {2018}, author = {Bethell, EJ and Dean, L and Smith, A and Bearder, SK}, title = {Celebrating 50 years of the Primate Society of Great Britain.}, journal = {Evolutionary anthropology}, volume = {27}, number = {2}, pages = {74-77}, doi = {10.1002/evan.21582}, pmid = {29575403}, issn = {1520-6505}, } @article {pmid29575373, year = {2018}, author = {Lorenzale, M and López-Unzu, MA and Rodríguez, C and Fernández, B and Durán, AC and Sans-Coma, V}, title = {The anatomical components of the cardiac outflow tract of chondrichthyans and actinopterygians.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1604-1619}, doi = {10.1111/brv.12411}, pmid = {29575373}, issn = {1469-185X}, abstract = {The outflow tract of the fish heart is the segment interposed between the ventricle and the ventral aorta. It holds the valves that prevent blood backflow from the gill vasculature to the ventricle. The anatomical composition, histological structure and evolutionary changes in the fish cardiac outflow tract have been under discussion for nearly two centuries and are still subject to debate. This paper offers a brief historical review of the main conceptions about the cardiac outflow tract components of chondrichthyans (cartilaginous fish) and actinopterygians (ray-finned fish) which have been put forward since the beginning of the nineteenth century up to the current day. We focus on the evolutionary origin of the outflow tract components and the changes to which they have been subject in the major extant groups of chondrichthyans and actinopterygians. In addition, an attempt is made to infer the primitive anatomical design of the heart of the gnathostomes (jawed vertebrates). Finally, several areas of further investigation are suggested. Recent work on fish heart morphology has shown that the cardiac outflow tract of chondrichthyans does not consist exclusively of the myocardial conus arteriosus as classically thought. A conus arteriosus and a bulbus arteriosus, devoid of myocardium and mainly composed of elastin and smooth muscle, are usually present in cartilaginous and ray-finned fish. This is consistent with the suggestion that both components coexisted from the onset of the gnathostome radiation. There is evidence that the conus arteriosus appeared in the agnathans. By contrast, the evolutionary origin of the bulbus is still unclear. It is almost certain that in all fish, both the conus and bulbus develop from the embryonic second heart field. We suggest herein that the primitive anatomical heart of the jawed vertebrates consisted of a sinus venosus containing the pacemaker tissue, an atrium possessing trabeculated myocardium, an atrioventricular region with compact myocardium which supported the atrioventricular valves, a ventricle composed of mixed myocardium, and an outflow tract consisting of a conus arteriosus, with compact myocardium in its wall and valves at its luminal side, and a non-myocardial bulbus arteriosus that connected the conus with the ventral aorta. Chondrichthyans have retained this basic anatomical design of the heart. In actinopterygians, the heart has been subject to notable changes during evolution. Among them, the following two should be highlighted: (i) a decrease in size of the conus in combination with a remarkable development of the bulbus, especially in teleosts; and (ii) loss of the myocardial compact layer of the ventricle in many teleost species.}, } @article {pmid29575348, year = {2018}, author = {Kotler, J and Haig, D}, title = {The tempo of human childhood: a maternal foot on the accelerator, a paternal foot on the brake.}, journal = {Evolutionary anthropology}, volume = {27}, number = {2}, pages = {80-91}, pmid = {29575348}, issn = {1520-6505}, mesh = {*Adrenarche ; Adult ; Anthropology, Physical ; *Biological Evolution ; Child ; Female ; *Genomic Imprinting ; Humans ; Male ; *Parent-Child Relations ; Puberty ; Weaning ; Young Adult ; }, abstract = {Relative to the life history of other great apes, that of humans is characterized by early weaning and short interbirth intervals (IBIs). We propose that in modern humans, birth until adrenarche, or the rise in adrenal androgens, developmentally corresponds to the period from birth until weaning in great apes and ancestral hominins. According to this hypothesis, humans achieved short IBIs by subdividing ancestral infancy into a nurseling phase, during which offspring fed at the breast, and a weanling phase, during which offspring fed specially prepared foods. Imprinted genes influence the timing of human weaning and adrenarche, with paternally expressed genes promoting delays in childhood maturation and maternally expressed genes promoting accelerated maturation. These observations suggest that the tempo of human development has been shaped by consequences for the fitness of kin, with faster development increasing maternal fitness at a cost to child fitness. The effects of imprinted genes suggest that the duration of the juvenile period (adrenarche until puberty) has also been shaped by evolutionary conflicts within the family.}, } @article {pmid29574894, year = {2018}, author = {Wang, D and Forstmeier, W and Ihle, M and Khadraoui, M and Jerónimo, S and Martin, K and Kempenaers, B}, title = {Irreproducible text-book "knowledge": The effects of color bands on zebra finch fitness.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {961-976}, doi = {10.1111/evo.13459}, pmid = {29574894}, issn = {1558-5646}, abstract = {Many fields of science-including behavioral ecology-currently experience a heated debate about the extent to which publication bias against null findings results in a misrepresentative scientific literature. Here, we show a case of an extreme mismatch between strong positive support for an effect in the literature and a failure to detect this effect across multiple attempts at replication. For decades, researchers working with birds have individually marked their study species with colored leg bands. For the zebra finch Taeniopygia guttata, a model organism in behavioral ecology, many studies over the past 35 years have reported effects of bands of certain colors on male or female attractiveness and further on behavior, physiology, life history, and fitness. Only eight of 39 publications presented exclusively null findings. Here, we analyze the results of eight experiments in which we quantified the fitness of a total of 730 color-banded individuals from four captive populations (two domesticated and two recently wild derived). This sample size exceeds the combined sample size of all 23 publications that clearly support the "color-band effect" hypothesis. We found that band color explains no variance in either male or female fitness. We also found no heterogeneity in color-band effects, arguing against both context and population specificity. Analysis of unpublished data from three other laboratories strengthens the generality of our null finding. Finally, a meta-analysis of previously published results is indicative of selective reporting and suggests that the effect size approaches zero when sample size is large. We argue that our field-and science in general-would benefit from more effective means to counter confirmation bias and publication bias.}, } @article {pmid29574604, year = {2018}, author = {Willett, CS and Wilson, EM}, title = {Evolution of Melanoma Antigen-A11 (MAGEA11) During Primate Phylogeny.}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {240-253}, pmid = {29574604}, issn = {1432-1432}, support = {P01-CA77739//National Cancer Institute/ ; }, abstract = {Melanoma antigen-A11 (MAGE-A11) is an X-linked and primate-specific steroid hormone receptor transcriptional coregulator and proto-oncogenic protein whose increased expression promotes the growth of prostate cancer. The MAGEA11 gene is expressed at low levels in normal human testis, ovary, and endometrium, and at highest levels in castration-resistant prostate cancer. Annotated genome predictions throughout the surviving primate lineage show that MAGEA11 acquired three 5' coding exons unique within the MAGEA subfamily during the evolution of New World monkeys (NWM), Old World monkeys (OWM), and apes. MAGE-A11 in all primates has a conserved FXXIF coactivator-binding motif that suggests interaction with p160 coactivators contributed to its early evolution as a transcriptional coregulator. An ancestral form of MAGE-A11 in the more distantly related lemur has significant amino acid sequence identity with human MAGE-A11, but lacks coregulator activity based on the absence of the three 5' coding exons that include a nuclear localization signal (NLS). NWM MAGE-A11 has greater amino acid sequence identity than lemur to human MAGE-A11, but inframe premature stop codons suggest that MAGEA11 is a pseudogene in NWM. MAGE-A11 in OWM and apes has nearly identical 5' coding exon amino acid sequence and conserved interaction sites for p300 acetyltransferase and cyclin A. We conclude that the evolution of MAGEA11 within the lineage leading to OWM and apes resulted in steroid hormone receptor transcriptional coregulator activity through the acquisition of three 5' coding exons that include a NLS sequence and nonsynonymous substitutions required to interact with cell cycle regulatory proteins and transcription factors.}, } @article {pmid29574478, year = {2018}, author = {Yan, DZ and Gan, YT and Zhou, H and Liu, J and Li, X}, title = {Correction to: Draft Genome Sequence of Cyclohexylamine-Degrading Strain Acinetobacter sp. YT-02 Isolated.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1470-8}, pmid = {29574478}, issn = {1432-0991}, abstract = {The original version of this article unfortunately contained a mistake in the Fig. S1 of supplementary material. It is corrected with this erratum.}, } @article {pmid29574330, year = {2018}, author = {Bittihn, P and Din, MO and Tsimring, LS and Hasty, J}, title = {Rational engineering of synthetic microbial systems: from single cells to consortia.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {92-99}, pmid = {29574330}, issn = {1879-0364}, support = {R01 GM069811/GM/NIGMS NIH HHS/United States ; }, abstract = {One promise of synthetic biology is to provide solutions for biomedical and industrial problems by rational design of added functionality in living systems. Microbes are at the forefront of this biological engineering endeavor due to their general ease of handling and their relevance in many potential applications from fermentation to therapeutics. In recent years, the field has witnessed an explosion of novel regulatory tools, from synthetic orthogonal transcription factors to posttranslational mechanisms for increased control over the behavior of synthetic circuits. Tool development has been paralleled by the discovery of principles that enable increased modularity and the management of host-circuit interactions. Engineered cell-to-cell communication bridges the scales from intracellular to population-level coordination. These developments facilitate the translation of more than a decade of circuit design into applications.}, } @article {pmid29574273, year = {2018}, author = {Psonis, N and Antoniou, A and Karameta, E and Leaché, AD and Kotsakiozi, P and Darriba, D and Kozlov, A and Stamatakis, A and Poursanidis, D and Kukushkin, O and Jablonski, D and Crnobrnja-Isailović, J and Gherghel, I and Lymberakis, P and Poulakakis, N}, title = {Resolving complex phylogeographic patterns in the Balkan Peninsula using closely related wall-lizard species as a model system.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {100-115}, doi = {10.1016/j.ympev.2018.03.021}, pmid = {29574273}, issn = {1095-9513}, mesh = {Animals ; Balkan Peninsula ; Bayes Theorem ; Biodiversity ; Calibration ; DNA, Mitochondrial/genetics ; Genetic Variation ; Genetics, Population ; Genomics ; Haplotypes/genetics ; Lizards/*classification/genetics ; Microsatellite Repeats/genetics ; *Models, Biological ; Phylogeny ; *Phylogeography ; Species Specificity ; }, abstract = {The Balkan Peninsula constitutes a biodiversity hotspot with high levels of species richness and endemism. The complex geological history of the Balkans in conjunction with the climate evolution are hypothesized as the main drivers generating this biodiversity. We investigated the phylogeography, historical demography, and population structure of closely related wall-lizard species from the Balkan Peninsula and southeastern Europe to better understand diversification processes of species with limited dispersal ability, from Late Miocene to the Holocene. We used several analytical methods integrating genome-wide SNPs (ddRADseq), microsatellites, mitochondrial and nuclear DNA data, as well as species distribution modelling. Phylogenomic analysis resulted in a completely resolved species level phylogeny, population level analyses confirmed the existence of at least two cryptic evolutionary lineages and extensive within species genetic structuring. Divergence time estimations indicated that the Messinian Salinity Crisis played a key role in shaping patterns of species divergence, whereas intraspecific genetic structuring was mainly driven by Pliocene tectonic events and Quaternary climatic oscillations. The present work highlights the effectiveness of utilizing multiple methods and data types coupled with extensive geographic sampling to uncover the evolutionary processes that shaped the species over space and time.}, } @article {pmid29574272, year = {2018}, author = {Barbosa, S and Paupério, J and Pavlova, SV and Alves, PC and Searle, JB}, title = {The Microtus voles: Resolving the phylogeny of one of the most speciose mammalian genera using genomics.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {85-92}, doi = {10.1016/j.ympev.2018.03.017}, pmid = {29574272}, issn = {1095-9513}, mesh = {Animals ; Arvicolinae/*classification/*genetics ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Genome ; *Genomics ; *Phylogeny ; }, abstract = {Sequential rapid radiations pose some of the greatest difficulties in phylogenetics, especially when analysing only a small number of genetic markers. Given that most of the speciation events occur in quick succession at various points in time, this creates particular challenges in determining phylogenetic relationships, i.e. branching order and divergence times. With the development of high throughput sequencing, thousands of markers can now readily be used to tackle these issues. Microtus is a speciose genus currently composed of 65 species that evolved over the last 2 million years. Although it is a well-studied group, there is still phylogenetic uncertainty at various divergence levels. Building upon previous studies that generally used small numbers of mitochondrial and/or nuclear loci, in this genomic-scale study we used both mitochondrial and nuclear data to study the rapid radiation within Microtus, using partial mitogenomes and genotyping-by-sequencing (GBS) on seven species representing five Microtus subgenera and the main biogeographic ranges where this group occurs. Both types of genome (mitochondrial and nuclear) generated similar tree topologies, with a basal split of the Nearctic (M. ochrogaster) and Holarctic (M. oeconomus) species, and then a subdivision of the five Palearctic species into two subgroups. These data support the occurrence of two European radiations, one North American radiation, and a later expansion of M. oeconomus from Asia to both Europe and North America. We further resolved the positioning of M. cabrerae as sister group of M. agrestis and refute the claim that M. cabrerae should be elevated to its own genus (Iberomys). Finally, the data support ongoing speciation events, especially within M. agrestis, with high levels of genetic divergence between the three Evolutionarily Significant Units (ESUs) previously identified. Similar high levels of divergence were also found among ESUs within M. oeconomus and M. arvalis.}, } @article {pmid29574271, year = {2018}, author = {De-Nova, JA and Sánchez-Reyes, LL and Eguiarte, LE and Magallón, S}, title = {Recent radiation and dispersal of an ancient lineage: The case of Fouquieria (Fouquiericeae, Ericales) in North American deserts.}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {92-104}, doi = {10.1016/j.ympev.2018.03.026}, pmid = {29574271}, issn = {1095-9513}, mesh = {Biodiversity ; *Desert Climate ; Ericales/*classification ; Fossils ; Genetic Speciation ; Geography ; Likelihood Functions ; North America ; *Phylogeny ; Software ; Time Factors ; United States ; }, abstract = {Arid biomes are particularly prominent in the Neotropics providing some of its most emblematic landscapes and a substantial part of its species diversity. To understand some of the evolutionary processes underlying the speciation of lineages in the Mexican Deserts, the diversification of Fouquieria is investigated, which includes eleven species, all endemic to the warm deserts and dry subtropical regions of North America. Using a phylogeny from plastid DNA sequences with samples of individuals from populations of all the species recognized in Fouquieria, we estimate divergence times, test for temporal diversification heterogeneity, test for geographical structure, and conduct ancestral area reconstruction. Fouquieria is an ancient lineage that diverged from Polemoniaceae ca. 75.54 Ma. A Mio-Pliocene diversification of Fouquieria with vicariance, associated with Neogene orogenesis underlying the early development of regional deserts is strongly supported. Test for temporal diversification heterogeneity indicates that during its evolutionary history, Fouquieria had a drastic diversification rate shift at ca.12.72 Ma, agreeing with hypotheses that some of the lineages in North American deserts diversified as early as the late Miocene to Pliocene, and not during the Pleistocene. Long-term diversification dynamics analyses suggest that extinction also played a significant role in Fouquieria's evolution, with a very high rate at the onset of the process. From the late Miocene onwards, Fouquieria underwent substantial diversification change, involving high speciation decreasing to the present and negligible extinction, which is congruent with its scant fossil record during this period. Geographic phylogenetic structure and the pattern of most sister species inhabiting different desert nucleus support that isolation by distance could be the main driver of speciation.}, } @article {pmid29574104, year = {2018}, author = {Schuldiner, S}, title = {The Escherichia coli effluxome.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {357-362}, doi = {10.1016/j.resmic.2018.02.006}, pmid = {29574104}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/metabolism/pharmacology ; Drug Resistance, Bacterial ; Escherichia coli/chemistry/drug effects/genetics/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; }, abstract = {Multidrug transporters function in a coordinated mode to provide an essential first-line defense mechanism that prevents antibiotics from reaching lethal concentrations, until a number of stable efficient adaptations occur that allow survival. Single-component efflux transporters remove the toxic compounds from the cytoplasm to the periplasmic space where TolC-dependent transporters expel them from the cell. The close interaction between the two types of transporters ensures handling of a wide range of xenobiotics and prevents rapid leak of the hydrophobic substrates back into the cell. In this review, we discuss the concept of the bacterial effluxome of the Gram-negative Escherichia coli that is the entire set of transporters expressed at a given time, under defined conditions. The process of identification of its members and the elucidation of the nature of the interactions throw a novel light on the roles of transporters in bacterial physiology and drug resistance development. We anticipate that the concept of an effluxome where each member contributes to the removal of noxious chemicals from the cell should contribute to improving the present strategy of searching for transport inhibitors as adjuvants of existing antibiotics and provide novel targets for this urgent undertaking.}, } @article {pmid29573818, year = {2018}, author = {Verheijen, J and Sleegers, K}, title = {Understanding Alzheimer Disease at the Interface between Genetics and Transcriptomics.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {6}, pages = {434-447}, doi = {10.1016/j.tig.2018.02.007}, pmid = {29573818}, issn = {0168-9525}, abstract = {Over 25 genes are known to affect the risk of developing Alzheimer disease (AD), the most common neurodegenerative dementia. However, mechanistic insights and improved disease management remains limited, due to difficulties in determining the functional consequences of genetic associations. Transcriptomics is increasingly being used to corroborate or enhance interpretation of genetic discoveries. These approaches, which include second and third generation sequencing, single-cell sequencing, and bioinformatics, reveal allele-specific events connecting AD risk genes to expression profiles, and provide converging evidence of pathophysiological pathways underlying AD. Simultaneously, they highlight brain region- and cell-type-specific expression patterns, and alternative splicing events that affect the straightforward relation between a genetic variant and AD, re-emphasizing the need for an integrated approach of genetics and transcriptomics in understanding AD.}, } @article {pmid29573817, year = {2018}, author = {}, title = {What Do You Think Makes a Good Undergraduate Laboratory Research Project?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {327-329}, doi = {10.1016/j.tig.2018.02.006}, pmid = {29573817}, issn = {0168-9525}, mesh = {Genetics/*trends ; Humans ; Research/*trends ; }, } @article {pmid29573376, year = {2018}, author = {Podmokła, E and Drobniak, SM and Rutkowska, J}, title = {Chicken or egg? Outcomes of experimental manipulations of maternally transmitted hormones depend on administration method - a meta-analysis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1499-1517}, doi = {10.1111/brv.12406}, pmid = {29573376}, issn = {1469-185X}, abstract = {Steroid hormones are important mediators of prenatal maternal effects in animals. Despite a growing number of studies involving experimental manipulation of these hormones, little is known about the impact of methodological differences among experiments on the final results expressed as offspring traits. Using a meta-analytical approach and a representative sample of experimental studies performed on birds, we tested the effect of two types of direct hormonal manipulations: manipulation of females (either by implantation of hormone pellets or injection of hormonal solutions) and manipulation of eggs by injection. In both types of manipulation we looked at the effects of two groups of hormones: corticosterone and androgens in the form of testosterone and androstenedione. We found that the average effect on offspring traits differed between the manipulation types, with a well-supported positive effect of egg manipulation and lack of a significant effect of maternal manipulation. The observed average positive effect for egg manipulation was driven mainly by androgen manipulations, while corticosterone manipulations exerted no overall effect, regardless of manipulation type. Detailed analyses revealed effects of varying size and direction depending on the specific offspring traits; e.g., egg manipulation positively affected physiology and behaviour (androgens), and negatively affected future reproduction (corticosterone). Effect size was negatively related to the dose of androgen injected into the eggs, but unrelated to timing of manipulation, offspring developmental stage at the time of measuring their traits, solvent type, the site of egg injection and maternal hormone delivery method. Despite the generally acknowledged importance of maternal hormones for offspring development in birds, the overall effect of their experimental elevation is rather weak, significantly heterogeneous and dependent on the hormone and type of manipulation. We conclude by providing general recommendations as to how hormonal manipulations should be performed in order to standardize their impact and the results achieved. We also emphasize the need for research on free-living birds with a focus on fitness-related and other long-term effects of maternal hormones.}, } @article {pmid29573372, year = {2018}, author = {Duhamel, S and Van Wambeke, F and Lefevre, D and Benavides, M and Bonnet, S}, title = {Mixotrophic metabolism by natural communities of unicellular cyanobacteria in the western tropical South Pacific Ocean.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2743-2756}, doi = {10.1111/1462-2920.14111}, pmid = {29573372}, issn = {1462-2920}, support = {OCE-1434916//National Science Foundation/ ; FP7/2007-2013//European Union's Seventh Framework Program/ ; ANR-14-CE01-0007-01//French research national agency/ ; //LEFE-CyBER program (CNRS-INSU)/ ; //GOPS program (IRD)/ ; //CNES/ ; }, abstract = {Cyanobacteria are major contributors to ocean biogeochemical cycling. However, mixotrophic metabolism and the relative importance of inorganic and organic carbon assimilation within the most abundant cyanobacteria are still poorly understood. We explore the ability of Prochlorococcus and Synechococcus to assimilate organic molecules with variable C:N:P composition and its modulation by light availability and photosynthetic impairment. We used a combination of radiolabelled molecules incubations with flow cytometry cell sorting to separate picoplankton groups from the western tropical South Pacific Ocean. Prochlorococcus and Synechococcus assimilated glucose, leucine and ATP at all stations, but cell-specific assimilation rates of N and P containing molecules were significantly higher than glucose. Incubations in the dark or with an inhibitor of photosystem II resulted in reduced assimilation rates. Light-enhanced cell-specific glucose uptake was generally higher for cyanobacteria (∼50%) than for the low nucleic acid fraction of bacterioplankton (LNA, ∼35%). Our results confirm previous findings, based mainly on cultures and genomic potentials, showing that Prochlorococcus and Synechococcus have a flexible mixotrophic metabolism, but demonstrate that natural populations remain primarily photoautotrophs. Our findings indicate that mixotrophy by marine cyanobacteria is more likely to be an adaptation to low inorganic nutrient availability rather than a facultative pathway for carbon acquisition.}, } @article {pmid29573371, year = {2018}, author = {Keim, CN and Duarte de Melo, R and Almeida, FP and Lins de Barros, HGP and Farina, M and Acosta-Avalos, D}, title = {Effect of applied magnetic fields on motility and magnetotaxis in the uncultured magnetotactic multicellular prokaryote 'Candidatus Magnetoglobus multicellularis'.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {465-474}, doi = {10.1111/1758-2229.12640}, pmid = {29573371}, issn = {1758-2229}, abstract = {Magnetotactic bacteria are found in the chemocline of aquatic environments worldwide. They produce nanoparticles of magnetic minerals arranged in chains in the cytoplasm, which enable these microorganisms to align to magnetic fields while swimming propelled by flagella. Magnetotactic bacteria are diverse phylogenetically and morphologically, including cocci, rods, vibria, spirilla and also multicellular forms, known as magnetotactic multicellular prokaryotes (MMPs). We used video-microscopy to study the motility of the uncultured MMP 'Candidatus Magnetoglobus multicellularis' under applied magnetic fields ranging from 0.9 to 32 Oersted (Oe). The bidimensional projections of the tridimensional trajectories where interpreted as plane projections of cylindrical helices and fitted as sinusoidal curves. The results showed that 'Ca. M. multicellularis' do not orient efficiently to low magnetic fields, reaching an efficiency of about 0.65 at 0.9-1.5 Oe, which are four to six times the local magnetic field. Good efficiency (0.95) is accomplished for magnetic fields ≥10 Oe. For comparison, unicellular magnetotactic microorganisms reach such efficiency at the local magnetic field. Considering that the magnetic moment of 'Ca. M. multicellularis' is sufficient for efficient alignment at the Earth's magnetic field, we suggest that misalignments are due to flagella movements, which could be driven by photo-, chemo- and/or other types of taxis.}, } @article {pmid29573367, year = {2018}, author = {Vasileva, D and Suzuki-Minakuchi, C and Kosono, S and Yoshida, M and Okada, K and Nojiri, H}, title = {Proteome and acylome analyses of the functional interaction network between the carbazole-degradative plasmid pCAR1 and host Pseudomonas putida KT2440.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {299-309}, doi = {10.1111/1758-2229.12639}, pmid = {29573367}, issn = {1758-2229}, abstract = {Understanding the interplay between a plasmid and its host system is a bottleneck towards prediction of the fate of plasmid-harbouring strains in the natural environments. Here, we studied the impact of the conjugative plasmid pCAR1, involved in carbazole degradation, on the proteome of Pseudomonas putida KT2440 using SILAC method. Furthermore, we investigated two acyl lysine modifications (acetylation and succinylation) that respond to the metabolic status of the cell and are implicated in regulation of various cellular processes. The total proteome analysis revealed that the abundance of key proteins involved in metabolism, signal transduction and motility was affected by pCAR1 carriage. In total, we identified 1359 unique acetylation sites on 637 proteins and 567 unique succinylation sites on 259 proteins. Changes in the acylation status of proteins involved in metabolism and translation by pCAR1 carriage were detected. Remarkably, acylation was identified on proteins involved in important plasmid functions, including partitioning and carbazole degradation, and on nucleoid-associated proteins that play a key role in the functional interaction with the chromosome. This study provides a novel insight on the functional consequences of plasmid carriage and improves our understanding of the plasmid-host cross-talk.}, } @article {pmid29573365, year = {2018}, author = {Meslier, V and Casero, MC and Dailey, M and Wierzchos, J and Ascaso, C and Artieda, O and McCullough, PR and DiRuggiero, J}, title = {Fundamental drivers for endolithic microbial community assemblies in the hyperarid Atacama Desert.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1765-1781}, doi = {10.1111/1462-2920.14106}, pmid = {29573365}, issn = {1462-2920}, abstract = {In hyperarid deserts, endolithic microbial communities colonize the rocks' interior as a survival strategy. Yet, the composition of these communities and the drivers promoting their assembly are still poorly understood. We analysed the diversity and community composition of endoliths from four different lithic substrates - calcite, gypsum, ignimbrite and granite - collected in the hyperarid zone of the Atacama Desert, Chile. By combining microscopy, mineralogy, spectroscopy and high throughput sequencing, we found these communities to be highly specific to their lithic substrate, although they were all dominated by the same four main phyla, Cyanobacteria, Actinobacteria, Chloroflexi and Proteobacteria. Our finding indicates a fine scale diversification of the microbial reservoir driven by substrate properties. The data suggest that the overall rock chemistry and the light transmission properties of the substrates are not essential drivers of community structure and composition. Instead, we propose that the architecture of the rock, i.e., the space available for colonization and its physical structure, linked to water retention capabilities, is ultimately the driver of community diversity and composition at the dry limit of life.}, } @article {pmid29573021, year = {2018}, author = {Keppner, EM and Ayasse, M and Steiger, S}, title = {Manipulation of parental nutritional condition reveals competition among family members.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {822-832}, doi = {10.1111/jeb.13266}, pmid = {29573021}, issn = {1420-9101}, abstract = {Parental care is thought to be costly, as it consumes time and energy. Such costs might be reduced in animal parents that raise their young on valuable food sources such as dung or carcasses, as parents are able to invest in self-maintenance by feeding from the same resource. However, this might lower the nutritional value for other family members and, as a consequence, food competition might arise. To promote our understanding of the outcome of such competition, we manipulated the necessity of parents to feed from the resource. Using a full factorial design, we paired food-deprived or well-fed males with food-deprived or well-fed females of burying beetles, which are known to raise their young on vertebrate cadavers. We found that food-deprived parents consumed more of the carrion than those that were well-fed and this had a negative impact on other family members. However, the outcome of the competition depended on the sex of the parents, with females suffering when males fed more and offspring suffering when females fed more. Thus, family life involves selfish elements, as both parents remove resources for the purpose of self-maintenance. However, females show altruistic aspects, as they appear to restrict their food consumption for the benefit of their offspring when paired with a food-deprived male. Interestingly, males extend their stay with the brood when having faced food scarcity prior to reproduction, presumably to replenish their energy reserves. Our study therefore reveals that breeding on shared resources can promote family living, but also results in competition.}, } @article {pmid29573004, year = {2018}, author = {Escudero, M and Hahn, M and Hipp, AL}, title = {RAD-seq linkage mapping and patterns of segregation distortion in sedges: meiosis as a driver of karyotypic evolution in organisms with holocentric chromosomes.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {833-843}, doi = {10.1111/jeb.13267}, pmid = {29573004}, issn = {1420-9101}, abstract = {Meiotic drive, the class of meiotic mechanisms that drive unequal segregation of alleles among gametes, may be an important force in karyotype evolution. Its role in holocentric organisms, whose chromosomes lack localized centromeres, is poorly understood. We crossed two individuals of Carex scoparia (Cyperaceae) with different chromosome numbers (2n = 33II = 66 × 2n = 32II = 64) to obtain F1 individuals, which we then self-pollinated to obtain second-generation (F2) crosses. RAD-seq was performed for 191 individuals (including the parents, five F1 individuals and 184 F2 individuals). Our F2 linkage map based on stringent editing of the RAD-seq data set yielded 32 linkage groups. In the final map, 865 loci were located on a linkage map of 3966.99 cM (linkage groups ranged from 24.39 to 193.31 cM in length and contained 5-51 loci each). Three linkage groups exhibit more loci under segregation distortion than expected by chance; within linkage groups, loci exhibiting segregation distortion are clustered. This finding implicates meiotic drive in the segregation of chromosome variants, suggesting that selection of chromosome variants in meiosis may contribute to the establishment and fixation of chromosome variants in Carex, which is renowned for high chromosomal and species diversity. This is an important finding as previous studies demonstrate that chromosome divergence may play a key role in differentiation and speciation in Carex.}, } @article {pmid29572526, year = {2018}, author = {Cabral, RB and Mayorga, J and Clemence, M and Lynham, J and Koeshendrajana, S and Muawanah, U and Nugroho, D and Anna, Z and Mira, and Ghofar, A and Zulbainarni, N and Gaines, SD and Costello, C}, title = {Rapid and lasting gains from solving illegal fishing.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {650-658}, doi = {10.1038/s41559-018-0499-1}, pmid = {29572526}, issn = {2397-334X}, abstract = {Perhaps the greatest challenge facing global fisheries is that recovery often requires substantial short-term reductions in fishing effort, catches and profits. These costs can be onerous and are borne in the present; thus, many countries are unwilling to undertake such socially and politically unpopular actions. We argue that many nations can recover their fisheries while avoiding these short-term costs by sharply addressing illegal, unreported and unregulated (IUU) fishing. This can spur fishery recovery, often at little or no cost to local economies or food provision. Indonesia recently implemented aggressive policies to curtail the high levels of IUU fishing it experiences from foreign-flagged vessels. We show that Indonesia's policies have reduced total fishing effort by at least 25%, illustrating with empirical evidence the possibility of achieving fishery reform without short-term losses to the local fishery economy. Compared with using typical management reforms that would require a 15% reduction in catch and 16% reduction in profit, the approach of curtailing IUU has the potential to generate a 14% increase in catch and a 12% increase in profit. Applying this model globally, we find that addressing IUU fishing could facilitate similar rapid, long-lasting fisheries gains in many regions of the world.}, } @article {pmid29572525, year = {2018}, author = {Johnson, AF and Lidström, S}, title = {The balance between concepts and complexity in ecology.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {585-587}, doi = {10.1038/s41559-018-0507-5}, pmid = {29572525}, issn = {2397-334X}, } @article {pmid29572524, year = {2018}, author = {Westgate, MJ and Haddaway, NR and Cheng, SH and McIntosh, EJ and Marshall, C and Lindenmayer, DB}, title = {Software support for environmental evidence synthesis.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {588-590}, doi = {10.1038/s41559-018-0502-x}, pmid = {29572524}, issn = {2397-334X}, } @article {pmid29572523, year = {2018}, author = {}, title = {Language lessons.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {579}, doi = {10.1038/s41559-018-0531-5}, pmid = {29572523}, issn = {2397-334X}, } @article {pmid29572430, year = {2018}, author = {Awasthi, S and Tompkins, J and Singhal, J and Riggs, AD and Yadav, S and Wu, X and Singh, S and Warden, C and Liu, Z and Wang, J and Slavin, TP and Weitzel, JN and Yuan, YC and Awasthi, M and Srivastava, SK and Awasthi, YC and Singhal, SS}, title = {Rlip depletion prevents spontaneous neoplasia in TP53 null mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3918-3923}, pmid = {29572430}, issn = {1091-6490}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; R01 CA077495/CA/NCI NIH HHS/United States ; R01 CA129383/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Female ; GTPase-Activating Proteins/*deficiency/genetics ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms/*genetics/metabolism/physiopathology/*prevention & control ; Tumor Suppressor Protein p53/*genetics/metabolism ; Tumor Suppressor Proteins/deficiency/metabolism ; }, abstract = {TP53 (p53) is a tumor suppressor whose functions are lost or altered in most malignancies. p53 homozygous knockout (p53-/-) mice uniformly die of spontaneous malignancy, typically T-cell lymphoma. RALBP1 (RLIP76, Rlip) is a stress-protective, mercapturic acid pathway transporter protein that also functions as a Ral effector involved in clathrin-dependent endocytosis. In stark contrast to p53-/- mice, Rlip-/- mice are highly resistant to carcinogenesis. We report here that partial Rlip deficiency induced by weekly administration of an Rlip-specific phosphorothioate antisense oligonucleotide, R508, strongly inhibited spontaneous as well as benzo(a)pyrene-induced carcinogenesis in p53-/- mice. This treatment effectively prevented large-scale methylomic and transcriptomic abnormalities suggestive of inflammation found in cancer-bearing p53-/- mice. The remarkable efficiency with which Rlip deficiency suppresses spontaneous malignancy in p53-/- mice has not been observed with any previously reported pharmacologic or genetic intervention. These findings are supported by cross-breeding experiments demonstrating that hemizygous Rlip deficiency also reduces the spontaneous malignancy phenotype of p53+/- mice. Rlip is found on the cell surface, and antibodies directed against Rlip were found to inhibit growth and promote apoptosis of cell lines as effectively as Rlip siRNA. The work presented here investigates several features, including oxidative DNA damage of the Rlip-p53 association in malignant transformation, and offers a paradigm for the mechanisms of tumor suppression by p53 and the prospects of suppressing spontaneous malignancy in hereditary cancer syndromes such as Li-Fraumeni.}, } @article {pmid29572429, year = {2018}, author = {Huang, L and Chen, PC and Liu, M and Fu, X and Gordiichuk, P and Yu, Y and Wolverton, C and Kang, Y and Mirkin, CA}, title = {Catalyst design by scanning probe block copolymer lithography.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3764-3769}, pmid = {29572429}, issn = {1091-6490}, abstract = {Scanning probe block copolymer lithography (SPBCL), in combination with density-functional theory (DFT), has been used to design and synthesize hydrogen evolution catalysts. DFT was used to calculate the hydrogen adsorption energy on a series of single-element, bimetallic, and trimetallic (Au, Pt, Ni, and Cu) substrates to provide leads that could be synthesized in the form of alloy or phase-separated particles via SPBCL. PtAuCu (18 nm, ∼1:1:1 stoichiometry) has been identified as a homogeneous alloy phase that behaves as an effective hydrogen evolution catalyst in acidic aqueous media, even when it is made in bulk form via solution phase methods. Significantly, the bulk-prepared PtAuCu/C nanocatalyst discovered via this process exhibits an activity seven times higher than that of the state-of-the-art commercial Pt/C catalyst (based upon Pt content). The advantage of using SPBCL in the discovery process is that one can uniformly make particles, each consisting of a uniform phase combination (e.g., all alloy or all phase-segregated species) at a fixed elemental ratio, an important consideration when working with polyelemental species where multiple phases may exist.}, } @article {pmid29572428, year = {2018}, author = {Kaleta, J and Wen, J and Magnera, TF and Dron, PI and Zhu, C and Michl, J}, title = {Structure of a monolayer of molecular rotors on aqueous subphase from grazing-incidence X-ray diffraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9373-9378}, pmid = {29572428}, issn = {1091-6490}, abstract = {In situ grazing-incidence X-ray scattering shows that a monolayer of artificial rod-shaped dipolar molecular rotors produced on the surface of an aqueous subphase in a Langmuir trough has a structure conducive to a 2D ferroelectric phase. The axes of the rotors stand an average of 0.83 nm apart in a triangular grid, perpendicular to the surface within experimental error. They carry 2,3-dichlorophenylene rotators near rod centers, between two decks of interlocked triptycenes installed axially on the rotor axle. The analysis is based first on simultaneous fitting of observed Bragg rods and second on fitting the reflectivity curve with only three adjustable parameters and the calculated rotor electron density, which also revealed the presence of about seven molecules of water near each rotator. Dependent on preparation conditions, a minor and variable amount of a different crystal phase may also be present in the monolayer.}, } @article {pmid29571614, year = {2018}, author = {Parker, HJ and Pushel, I and Krumlauf, R}, title = {Coupling the roles of Hox genes to regulatory networks patterning cranial neural crest.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.03.016}, pmid = {29571614}, issn = {1095-564X}, abstract = {The neural crest is a transient population of cells that forms within the developing central nervous system and migrates away to generate a wide range of derivatives throughout the body during vertebrate embryogenesis. These cells are of evolutionary and clinical interest, constituting a key defining trait in the evolution of vertebrates and alterations in their development are implicated in a high proportion of birth defects and craniofacial abnormalities. In the hindbrain and the adjacent cranial neural crest cells (cNCCs), nested domains of Hox gene expression provide a combinatorial'Hox-code' for specifying regional properties in the developing head. Hox genes have been shown to play important roles at multiple stages in cNCC development, including specification, migration, and differentiation. However, relatively little is known about the underlying gene-regulatory mechanisms involved, both upstream and downstream of Hox genes. Furthermore, it is still an open question as to how the genes of the neural crest GRN are linked to Hox-dependent pathways. In this review, we describe Hox gene expression, function and regulation in cNCCs with a view to integrating these genes within the emerging gene regulatory network for cNCC development. We highlight early roles for Hox1 genes in cNCC specification, proposing that this may be achieved, in part, by regulation of the balance between pluripotency and differentiation in precursor cells within the neuro-epithelium. We then describe what is known about the regulation of Hox gene expression in cNCCs and discuss this from the perspective of early vertebrate evolution.}, } @article {pmid29571613, year = {2018}, author = {Gigante, ED and Long, AB and Ben-Ami, J and Caspary, T}, title = {Hypomorphic Smo mutant with inefficient ciliary enrichment disrupts the highest level of vertebrate Hedgehog response.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {152-162}, pmid = {29571613}, issn = {1095-564X}, support = {R01 NS090029/NS/NINDS NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; R35 GM122549/GM/NIGMS NIH HHS/United States ; R01 GM110663/GM/NIGMS NIH HHS/United States ; R01 NS056380/NS/NINDS NIH HHS/United States ; T32 NS096050/NS/NINDS NIH HHS/United States ; P30 NS055077/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/genetics ; Cell Culture Techniques ; Cilia/*metabolism ; Hedgehog Proteins/*metabolism ; Mice ; Mutation ; Organogenesis/genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; Smoothened Receptor/*genetics ; Vertebrates/metabolism ; }, abstract = {Smoothened (Smo) is the essential transducer of Sonic hedgehog (Shh) signaling, which regulates cell fate and proliferation during embryogenesis. We identified a novel mouse mutant, cabbie (cbb), and found that its cause is a missense mutation in Smo. We showed the Smocbb mutation is insensitive to the Shh agonist SAG, perhaps due to the disruption of SAG binding. We characterized Smocbb for defects in craniofacial and skeletal development, as well as neural tube patterning, and revealed Smocbb affected processes that require the highest levels of Shh activity. Smo is normally enriched in cilia upon Shh stimulation; however, we detected inefficient enrichment of Smo in Smocbb mutants whether we stimulated with Shh or SAG. Taken together, our data suggest that the highest levels of vertebrate Hedgehog signaling activity require efficient Smo ciliary enrichment.}, } @article {pmid29571612, year = {2018}, author = {Belus, MT and Rogers, MA and Elzubeir, A and Josey, M and Rose, S and Andreeva, V and Yelick, PC and Bates, EA}, title = {Kir2.1 is important for efficient BMP signaling in mammalian face development.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29571612}, issn = {1095-564X}, support = {R56 DE025311/DE/NIDCR NIH HHS/United States ; }, abstract = {Mutations that disrupt the inwardly rectifying potassium channel Kir2.1 lead to Andersen-Tawil syndrome that includes periodic paralysis, cardiac arrhythmia, cognitive deficits, craniofacial dysmorphologies and limb defects. The molecular mechanism that underlies the developmental consequences of inhibition of these channels has remained a mystery. We show that while loss of Kir2.1 function does not affect expression of several early facial patterning genes, the domain in which Pou3f3 is expressed in the maxillary arch is reduced. Pou3f3 is important for development of the jugal and squamosal bones. The reduced expression domain of Pou3f3 is consistent with the reduction in the size of the squamosal and jugal bones in Kcnj2KO/KO animals, however it does not account for the diverse craniofacial defects observed in Kcnj2KO/KO animals. We show that Kir2.1 function is required in the cranial neural crest for morphogenesis of several craniofacial structures including palate closure. We find that while the palatal shelves of Kir2.1-null embryos elevate properly, they are reduced in size due to decreased proliferation of the palatal mesenchyme. While we find no reduction in expression of BMP ligands, receptors, and associated Smads in this setting, loss of Kir2.1 reduces the efficacy of BMP signaling as shown by the reduction of phosphorylated Smad 1/5/8 and reduced expression of BMP targets Smad6 and Satb2.}, } @article {pmid29571611, year = {2018}, author = {Borensztejn, A and Mascaro, A and Wharton, KA}, title = {JAK/STAT signaling prevents excessive apoptosis to ensure maintenance of the interfollicular stalk critical for Drosophila oogenesis.}, journal = {Developmental biology}, volume = {438}, number = {1}, pages = {1-9}, pmid = {29571611}, issn = {1095-564X}, support = {P40 OD018537/OD/NIH HHS/United States ; R01 GM068118/GM/NIGMS NIH HHS/United States ; T32 GM007601/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/*genetics ; Cell Count ; Drosophila/metabolism ; Drosophila Proteins/metabolism ; Female ; Immunohistochemistry ; Janus Kinases/*metabolism ; Oogenesis/*genetics/physiology ; Ovarian Follicle/cytology/physiology ; Ovary/*cytology/metabolism/physiology ; STAT Transcription Factors/*metabolism ; Signal Transduction/physiology ; }, abstract = {Apoptosis not only eliminates cells that are damaged or dangerous but also cells whose function during development in patterning or organogenesis is complete. The successful formation of germ cells is essential for the perpetuation of a species. The production of an oocyte often depends on signaling between germline and somatic cells, but also between specialized types of somatic cells. In Drosophila, each developing egg chamber is separated from the next by a single file of interfollicular somatic cells. Little is known about the function of the interfollicular stalk, although its presumed role in separating egg chambers is to ensure that patterning cues from one egg chamber do not impact or disrupt the development of adjacent egg chambers. We found that cells comprising the stalk undergo a progressive decrease in number during oogenesis through an apoptotic-dependent loss. The extent of programmed cell death is restricted by JAK/STAT signaling in a cell-autonomous manner to ensure that the stalk is maintained. Both a failure to undergo the normal reduction in stalk cell number, or to prevent excessive stalk cell apoptosis results in a decrease in fecundity. Thus, activation of JAK/STAT signaling in the Drosophila interfollicular stalk emerges as a model to study the tight regulation of signaling-dependent apoptosis.}, } @article {pmid29571610, year = {2018}, author = {Nardi, JB and Bee, CM and Wallace, CL}, title = {Remodeling of the abdominal epithelial monolayer during the larva-pupa-adult transformation of Manduca.}, journal = {Developmental biology}, volume = {438}, number = {1}, pages = {10-22}, doi = {10.1016/j.ydbio.2018.03.017}, pmid = {29571610}, issn = {1095-564X}, mesh = {Animals ; Apoptosis/physiology ; Drosophila/growth & development ; Epithelial Cells/*physiology ; Humans ; Larva/cytology/*growth & development ; Manduca/*embryology ; Metamorphosis, Biological/*physiology ; Pupa/cytology/*growth & development ; }, abstract = {During metamorphosis of insect epithelial monolayers, cells die, divide, and rearrange. In Drosophila undifferentiated diploid cells destined to form the adult cuticle of each abdominal segment segregate early in development from the surrounding polyploid larval epithelial cells of that segment as eight groups of diploid histoblast cells. The larval polyploid cells are programmed to die and be replaced by divisions and rearrangements of histoblast cells. By contrast, abdominal epithelial cells of Manduca larvae form a monolayer of cells representing different ploidy levels with no definitive segregation of diploid cells destined to form adult structures. These epithelial cells of mixed ploidy levels produce a thick smooth larval cuticle with sparsely distributed sensory bristles. Adult descendants of this larval monolayer produce a thinner cuticle with densely packed scale cells. The transition between these differentiated states of Manduca involves divisions of cells, changes in ploidy levels, and sorting of certain polyploid cells into circular rosette patches to minimize contacts of these polyploid cells with surrounding cells of equal or smaller size. Cells within the rosettes and some surrounding cells are destined to die and be replaced by remaining epithelial cells of uniform size and ploidy at pupa-adult apolysis.}, } @article {pmid29571286, year = {2018}, author = {Zhao, Z and Tseng, YC and Peng, Z and Lopez, Y and Chen, CY and Tillman, BL and Dang, P and Wang, J}, title = {Refining a major QTL controlling spotted wilt disease resistance in cultivated peanut (Arachis hypogaea L.) and evaluating its contribution to the resistance variations in peanut germplasm.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {17}, pmid = {29571286}, issn = {1471-2156}, abstract = {BACKGROUND: Spotted wilt, caused by tomato spotted wilt virus (TSWV), has been one of major diseases in cultivated peanut grown in the southeastern United States (US) since 1990. Previously a major quantitative trait locus (QTL) controlling spotted wilt disease resistance was mapped to an interval of 2.55 cM genetic distance corresponding to a physical distance of 14.4 Mb on chromosome A01 of peanut by using a segregating F2 population. The current study focuses on refining this major QTL region and evaluating its contributions in the US peanut mini-core germplasm.

RESULTS: Two simple sequence repeat (SSR) markers associated with the major QTL were used to genotype F5 individuals, and 25 heterozygous individuals were selected and developed into an F6 segregating population. Based on visual evaluation in the field, a total of 194 susceptible F6 individuals were selected and planted into F7 generation for phenotyping. Nine SSR markers were used to genotype the 194 F6 individuals, and QTL analysis revealed that a confidence interval of 15.2 Mb region had the QTL with 22.8% phenotypic variation explained (PVE). This QTL interval was further genotyped using the Amplicon-seq method. A total of 81 non-redundant single nucleotide polymorphism (SNP) and eight InDel markers were detected. No recombinant was detected among the F6 individuals. Two InDel markers were integrated into the linkage group and helped to refine the confidence interval of this QTL into a 0.8 Mb region. To test the QTL contributes to the resistance variance in US peanut mini-core germplasm, two flanking SSR markers were used to genotype 107 mini-core germplasm accessions. No statistically significant association was observed between the genotype at the QTL region and spotted wilt resistance in the mini-core germplasm, which indicated that the resistance allelic region at this QTL didn't contribute to the resistance variance in the US peanut mini-core germplasm, thus was a unique resistance source.

CONCLUSION: A major QTL related to spotted wilt disease resistance in peanut was refined to a 0.8 Mb region on A01 chromosome, which didn't relate to spotted wilt disease resistance in the US peanut mini-core germplasm and might be a unique genetic source.}, } @article {pmid29570445, year = {2018}, author = {Choi, S and Kang, JW and Kim, MS and Yoon, JH and Seong, CN}, title = {Dokdonia aurantiaca sp. nov., isolated from seaweed Zostera marina.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1697-1701}, doi = {10.1099/ijsem.0.002730}, pmid = {29570445}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seaweed/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; Zosteraceae/*microbiology ; }, abstract = {A non-motile, orange-coloured and rod-shaped bacterial strain, designated strain ZOW29T, was isolated from a seaweed sample collected from the South Sea, Republic of Korea. Cells were Gram-stain-negative, aerobic and non-motile. The isolate required sea salts for growth. Carotenoid pigment was produced. A phylogenetic tree based on 16S rRNA gene sequences showed that strain ZOW29T forms an evolutionary lineage within the radiation enclosing the members of the genus Dokdonia with Dokdonia diaphoros MSKK-32T, Dokdonia eikasta PMA-26Tand Dokdonia donghaensis DSW-1T (97.1 % sequence similarity each) as its nearest neighbours. The DNA-DNA relatedness values between strain ZOW29T and these four type strains were 35-48 %. The major fatty acids were iso-C15:0, iso-C17 : 0 3-OH and iso-C15 : 1 G. Strain ZOW29T contained MK-6 and phosphatidylethanolamine, an unidentified aminolipid and an unidentified polar lipid as the only isoprenoid quinone and the major polar lipids, respectively. The DNA G+C content of strain ZOW29T was 38 mol%. On the basis of polyphasic characterization, it is suggested that the isolate represents a novel species of the genus Dokdonia, for which the name Dokdonia aurantiaca sp. nov. (type strain, ZOW29T=KCTC 52956T=JCM 32295T) is proposed.}, } @article {pmid29570444, year = {2018}, author = {Chang, R and Bird, L and Barr, C and Osburn, M and Wilbanks, E and Nealson, K and Rowe, A}, title = {Thioclava electrotropha sp. nov., a versatile electrode and sulfur-oxidizing bacterium from marine sediments.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1652-1658}, doi = {10.1099/ijsem.0.002723}, pmid = {29570444}, issn = {1466-5034}, mesh = {Autotrophic Processes ; Bacterial Typing Techniques ; Base Composition ; California ; DNA, Bacterial/genetics ; Electrodes ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Salinity ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {A taxonomic and physiologic characterization was carried out on Thioclava strain ElOx9T, which was isolated from a bacterial consortium enriched on electrodes poised at electron donating potentials. The isolate is Gram-negative, catalase-positive and oxidase-positive; the cells are motile short rods. The bacterium is facultatively anaerobic with the ability to utilize nitrate as an electron acceptor. Autotrophic growth with H2 and S0 (oxidized to sulfate) was observed. The isolate also grows heterotrophically with organic acids and sugars. Growth was observed at salinities from 0 to 10% NaCl and at temperatures from 15 to 41 °C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain belongs in the genus Thioclava; it had the highest sequence similarity of 98.8 % to Thioclava atlantica 13D2W-2T, followed by Thioclava dalianensis DLFJ1-1T with 98.5 % similarity, Thioclava pacifica TL 2T with 97.7 % similarity, and then Thioclava indica DT23-4T with 96.9 %. All other sequence similarities were below 97 % to characterized strains. The digital DNA-DNA hybridization estimated when compared to T. atlantica 13D2W-2T, T. dalianensis DLFJ1-1T, T. pacifica TL 2T and T. indica DT23-4T were 15.8±2.1, 16.7+2.1, 14.3±1.9 and 18.3±2.1 %. The corresponding average nucleotide identity values between these strains were determined to be 65.1, 67.8, 68.4 and 64.4 %, respectively. The G+C content of the chromosomal DNA is 63.4 mol%. Based on these results, a novel species Thioclava electrotropha sp. nov. is proposed, with the type strain ElOx9T (=DSM 103712T=ATCC TSD-100T).}, } @article {pmid29570408, year = {2018}, author = {Snyder, RE and Ellner, SP}, title = {Pluck or Luck: Does Trait Variation or Chance Drive Variation in Lifetime Reproductive Success?.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {E90-E107}, doi = {10.1086/696125}, pmid = {29570408}, issn = {1537-5323}, abstract = {While there has been extensive interest in how intraspecific trait variation affects ecological processes, outcomes are highly variable even when individuals are identical: some are lucky, while others are not. Trait variation is therefore important only if it adds substantially to the variability produced by luck. We ask when trait variation has a substantial effect on variability in lifetime reproductive success (LRS), using two approaches: (1) we partition the variation in LRS into contributions from luck and trait variation and (2) we ask what can be inferred about an individual's traits and with what certainty, given their observed LRS. In theoretical stage- and size-structured models and two empirical case studies, we find that luck usually dominates the variance of LRS. Even when individuals differ substantially in ways that affect expected LRS, unless the effects of luck are substantially reduced (e.g., low variability in reproductive life span or annual fecundity), most variance in lifetime outcomes is due to luck, implying that departures from "null" models omitting trait variation will be hard to detect. Luck also obscures the relationship between realized LRS and individual traits. While trait variation may influence the fate of populations, luck often governs the lives of individuals.}, } @article {pmid29570407, year = {2018}, author = {Rapkin, J and Jensen, K and Archer, CR and House, CM and Sakaluk, SK and Castillo, ED and Hunt, J}, title = {The Geometry of Nutrient Space-Based Life-History Trade-Offs: Sex-Specific Effects of Macronutrient Intake on the Trade-Off between Encapsulation Ability and Reproductive Effort in Decorated Crickets.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {452-474}, doi = {10.1086/696147}, pmid = {29570407}, issn = {1537-5323}, abstract = {Life-history theory assumes that traits compete for limited resources, resulting in trade-offs. The most commonly manipulated resource in empirical studies is the quantity or quality of diet. Recent studies using the geometric framework for nutrition, however, suggest that trade-offs are often regulated by the intake of specific nutrients, but a formal approach to identify and quantify the strength of such trade-offs is lacking. We posit that trade-offs occur whenever life-history traits are maximized in different regions of nutrient space, as evidenced by nonoverlapping 95% confidence regions of the global maximum for each trait and large angles (θ) between linear nutritional vectors and Euclidean distances (d) between global maxima. We then examined the effects of protein and carbohydrate intake on the trade-off between reproduction and aspects of immune function in male and female Gryllodes sigillatus. Female encapsulation ability and egg production increased with the intake of both nutrients, whereas male encapsulation ability increased with protein intake but calling effort increased with carbohydrate intake. The trade-offs between traits was therefore larger in males than in females, as demonstrated by significant negative correlations between the traits in males, nonoverlapping 95% confidence regions, and larger estimates of θ and d. Under dietary choice, the sexes had similar regulated intakes, but neither optimally regulated nutrient intake for maximal trait expression. We highlight the fact that greater consideration of specific nutrient intake is needed when examining nutrient space-based trade-offs.}, } @article {pmid29570406, year = {2018}, author = {Coelho, MTP and Rangel, TF}, title = {Neutral Community Dynamics and the Evolution of Species Interactions.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {421-434}, doi = {10.1086/696216}, pmid = {29570406}, issn = {1537-5323}, abstract = {A contemporary goal in ecology is to determine the ecological and evolutionary processes that generate recurring structural patterns in mutualistic networks. One of the great challenges is testing the capacity of neutral processes to replicate observed patterns in ecological networks, since the original formulation of the neutral theory lacks trophic interactions. Here, we develop a stochastic-simulation neutral model adding trophic interactions to the neutral theory of biodiversity. Without invoking ecological differences among individuals of different species, and assuming that ecological interactions emerge randomly, we demonstrate that a spatially explicit multitrophic neutral model is able to capture the recurrent structural patterns of mutualistic networks (i.e., degree distribution, connectance, nestedness, and phylogenetic signal of species interactions). Nonrandom species distribution, caused by probabilistic events of migration and speciation, create nonrandom network patterns. These findings have broad implications for the interpretation of niche-based processes as drivers of ecological networks, as well as for the integration of network structures with demographic stochasticity.}, } @article {pmid29570405, year = {2018}, author = {Voje, KL and Starrfelt, J and Liow, LH}, title = {Model Adequacy and Microevolutionary Explanations for Stasis in the Fossil Record.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {509-523}, doi = {10.1086/696265}, pmid = {29570405}, issn = {1537-5323}, abstract = {Long-term phenotypic stasis is frequently observed in the fossil record, but not readily predicted from microevolutionary theory. To test competing explanations for stasis on macroevolutionary timescales we need reliably estimated parameters from appropriate evolutionary models that adequately describe the evolutionary trait dynamics. Here, we develop tests to assess the adequacy of the most commonly used stasis model in evolutionary biology and apply them to time series of phenotypic traits from fossil lineages. Of the 572 fossil time series we analyzed from the literature, 263 time series showed a better fit to the stasis model relative to alternative models, but only 172 of those fitted the stasis model in both relative and absolute terms. The estimated trait variances from these 172 time series do not correlate with rough proxies of effective population size. Our preliminary investigation of the fixed-optimum hypothesis hence fails to give empirical support to the idea that genetic drift around a constant trait optimum is an explanation for stasis in the fossil record. We argue that optima following stationary processes on the adaptive landscape is a viable hypothesis for stasis that needs further investigation. We end by discussing how investigations of model adequacy can be a valuable approach for increasing our understanding of the dynamics of the adaptive landscape on macroevolutionary timescales.}, } @article {pmid29570404, year = {2018}, author = {Meuthen, D and Baldauf, SA and Bakker, TCM and Thünken, T}, title = {Neglected Patterns of Variation in Phenotypic Plasticity: Age- and Sex-Specific Antipredator Plasticity in a Cichlid Fish.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {475-490}, doi = {10.1086/696264}, pmid = {29570404}, issn = {1537-5323}, abstract = {The ability of organisms to plastically respond to changing environments is well studied. However, variation in phenotypic plasticity during ontogeny is less well understood despite its relevance of being an important source of phenotypic variation in nature. Here, we comprehensively study ontogenetic variation in morphological antipredator plasticity across multiple traits in Pelvicachromis taeniatus, a western African cichlid fish with sexually dimorphic ornamentation. In a split-clutch design, fish were raised under different levels of perceived predation risk (conspecific alarm cues or distilled water). Morphological plasticity varied substantially across ontogeny: it was first observable at an early juvenile stage where alarm cue-exposed fish grew faster. Subsequently, significant plasticity was absent until the onset of sexual maturity. Here, alarm cue-exposed males were larger than control males, which led to deeper bodies, longer dorsal spines, larger caudal peduncles, and increased eye diameters. Sexual ornamentation emerged delayed in alarm cue-exposed males. In later adulthood, the plastic responses receded. Despite small effect sizes, these responses represent putative adaptive plasticity, as they are likely to reduce predation risk. In females, we did not observe any plasticity. In accordance with theory, these results suggest fine-tuned expression of plasticity that potentially increases defenses during vulnerable developmental stages and reproductive output.}, } @article {pmid29570403, year = {2018}, author = {Youngsteadt, E and Irwin, RE and Fowler, A and Bertone, MA and Giacomini, SJ and Kunz, M and Suiter, D and Sorenson, CE}, title = {Venus Flytrap Rarely Traps Its Pollinators.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {539-546}, doi = {10.1086/696124}, pmid = {29570403}, issn = {1537-5323}, abstract = {Because carnivorous plants rely on arthropods as pollinators and prey, they risk consuming would-be mutualists. We examined this potential conflict in the Venus flytrap (Dionaea muscipula), whose pollinators were previously unknown. Diverse arthropods from two classes and nine orders visited flowers; 56% of visitors carried D. muscipula pollen, often mixed with pollen of coflowering species. Within this diverse, generalized community, certain bee and beetle species appear to be the most important pollinators, on the basis of their abundance, pollen load size, and pollen fidelity. Dionaea muscipula prey spanned four invertebrate classes and 11 orders; spiders, beetles, and ants were most common. At the family and species levels, few taxa were shared between traps and flowers, yielding a near-zero value of niche overlap for these potentially competing structures. Spatial separation of traps and flowers may contribute to partitioning the invertebrate community between nutritional and reproductive functions in D. muscipula.}, } @article {pmid29570402, year = {2018}, author = {Walter, GM and Aguirre, JD and Blows, MW and Ortiz-Barrientos, D}, title = {Evolution of Genetic Variance during Adaptive Radiation.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {E108-E128}, doi = {10.1086/696123}, pmid = {29570402}, issn = {1537-5323}, abstract = {Genetic correlations between traits can concentrate genetic variance into fewer phenotypic dimensions that can bias evolutionary trajectories along the axis of greatest genetic variance and away from optimal phenotypes, constraining the rate of evolution. If genetic correlations limit adaptation, rapid adaptive divergence between multiple contrasting environments may be difficult. However, if natural selection increases the frequency of rare alleles after colonization of new environments, an increase in genetic variance in the direction of selection can accelerate adaptive divergence. Here, we explored adaptive divergence of an Australian native wildflower by examining the alignment between divergence in phenotype mean and divergence in genetic variance among four contrasting ecotypes. We found divergence in mean multivariate phenotype along two major axes represented by different combinations of plant architecture and leaf traits. Ecotypes also showed divergence in the level of genetic variance in individual traits and the multivariate distribution of genetic variance among traits. Divergence in multivariate phenotypic mean aligned with divergence in genetic variance, with much of the divergence in phenotype among ecotypes associated with changes in trait combinations containing substantial levels of genetic variance. Overall, our results suggest that natural selection can alter the distribution of genetic variance underlying phenotypic traits, increasing the amount of genetic variance in the direction of natural selection and potentially facilitating rapid adaptive divergence during an adaptive radiation.}, } @article {pmid29570401, year = {2018}, author = {Laird, RA and Schamp, BS}, title = {Calculating Competitive Intransitivity: Computational Challenges.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {547-552}, doi = {10.1086/696266}, pmid = {29570401}, issn = {1537-5323}, abstract = {Intransitive (or "rock-paper-scissors") competition is compelling because it promotes species coexistence and because recent work suggests that it may be common in natural systems. One class of intransitivity indices works by considering s, the minimum number of competitive reversals to convert a given competitive community (i.e., a "tournament") to a hierarchy. The most straightforward example of such "reversal-based" indices is Petraitis's index, [Formula: see text], where M is the maximum s across all possible n-species tournaments. Using exhaustive searches, we prove that Petraitis's formula for M (and, therefore, t) does not hold for [Formula: see text]. Furthermore, determination of s for even moderate values of n may prove difficult, as the equivalent graph theoretical problem is NP (nondeterministic polynomial time) hard; there is no known computationally feasible way to compute an exact answer for anything but small values of n, let alone a closed-form solution. Petraitis's t is a valuable index of intransitivity; however, at present its use is limited to relatively species-poor systems. More broadly, reversal-based indices, while intuitive, may be problematic because of this computability issue.}, } @article {pmid29570400, year = {2018}, author = {Fourtune, L and Prunier, JG and Paz-Vinas, I and Loot, G and Veyssière, C and Blanchet, S}, title = {Inferring Causalities in Landscape Genetics: An Extension of Wright's Causal Modeling to Distance Matrices.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {491-508}, doi = {10.1086/696233}, pmid = {29570400}, issn = {1537-5323}, abstract = {Identifying landscape features that affect functional connectivity among populations is a major challenge in fundamental and applied sciences. Landscape genetics combines landscape and genetic data to address this issue, with the main objective of disentangling direct and indirect relationships among an intricate set of variables. Causal modeling has strong potential to address the complex nature of landscape genetic data sets. However, this statistical approach was not initially developed to address the pairwise distance matrices commonly used in landscape genetics. Here, we aimed to extend the applicability of two causal modeling methods-that is, maximum-likelihood path analysis and the directional separation test-by developing statistical approaches aimed at handling distance matrices and improving functional connectivity inference. Using simulations, we showed that these approaches greatly improved the robustness of the absolute (using a frequentist approach) and relative (using an information-theoretic approach) fits of the tested models. We used an empirical data set combining genetic information on a freshwater fish species (Gobio occitaniae) and detailed landscape descriptors to demonstrate the usefulness of causal modeling to identify functional connectivity in wild populations. Specifically, we demonstrated how direct and indirect relationships involving altitude, temperature, and oxygen concentration influenced within- and between-population genetic diversity of G. occitaniae.}, } @article {pmid29570399, year = {2018}, author = {Shocket, MS and Strauss, AT and Hite, JL and Šljivar, M and Civitello, DJ and Duffy, MA and Cáceres, CE and Hall, SR}, title = {Temperature Drives Epidemics in a Zooplankton-Fungus Disease System: A Trait-Driven Approach Points to Transmission via Host Foraging.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {435-451}, doi = {10.1086/696096}, pmid = {29570399}, issn = {1537-5323}, abstract = {Climatic warming will likely have idiosyncratic impacts on infectious diseases, causing some to increase while others decrease or shift geographically. A mechanistic framework could better predict these different temperature-disease outcomes. However, such a framework remains challenging to develop, due to the nonlinear and (sometimes) opposing thermal responses of different host and parasite traits and due to the difficulty of validating model predictions with observations and experiments. We address these challenges in a zooplankton-fungus (Daphnia dentifera-Metschnikowia bicuspidata) system. We test the hypothesis that warmer temperatures promote disease spread and produce larger epidemics. In lakes, epidemics that start earlier and warmer in autumn grow much larger. In a mesocosm experiment, warmer temperatures produced larger epidemics. A mechanistic model parameterized with trait assays revealed that this pattern arose primarily from the temperature dependence of transmission rate (β), governed by the increasing foraging (and, hence, parasite exposure) rate of hosts (f). In the trait assays, parasite production seemed sufficiently responsive to shape epidemics as well; however, this trait proved too thermally insensitive in the mesocosm experiment and lake survey to matter much. Thus, in warmer environments, increased foraging of hosts raised transmission rate, yielding bigger epidemics through a potentially general, exposure-based mechanism for ectotherms. This mechanistic approach highlights how a trait-based framework will enhance predictive insight into responses of infectious disease to a warmer world.}, } @article {pmid29570398, year = {2018}, author = {Wood, CW and Wice, EW and Del Sol, J and Paul, S and Sanderson, BJ and Brodie, ED}, title = {Constraints Imposed by a Natural Landscape Override Offspring Fitness Effects to Shape Oviposition Decisions in Wild Forked Fungus Beetles.}, journal = {The American naturalist}, volume = {191}, number = {4}, pages = {524-538}, doi = {10.1086/696218}, pmid = {29570398}, issn = {1537-5323}, abstract = {Oviposition site decisions often maximize offspring fitness, but costs constraining choice can cause females to oviposit in poor developmental environments. It is unclear whether these constraints cumulatively outweigh offspring fitness to determine oviposition decisions in wild populations. Understanding how constraints shape oviposition in natural landscapes is a critical step toward revealing how maternal behavior influences fundamental phenomena like the evolution of specialization and the use of sink environments. Here, we used a genetic capture-recapture technique to reconstruct the oviposition decisions of individual females in a natural metapopulation of a beetle (Bolitotherus cornutus) that oviposits on three fungus species. We measured larval fitness-related traits (mass, development time, survival) on each fungus and compared the oviposition preferences of females in laboratory versus field tests. Larval fitness differed substantially among fungi, and females preferred a high-quality (high larval fitness) fungus in laboratory trials. However, females frequently laid eggs on the lowest-quality fungus in the wild. They preferred high-quality fungi when moving between oviposition sites, but this preference disappeared as the distance between sites increased and was inconsistent between study plots. Our results suggest that constraints on oviposition preferences in natural landscapes are sufficiently large to drive oviposition in poor developmental environments even when offspring fitness consequences are severe.}, } @article {pmid29570365, year = {2018}, author = {Wang, YY and Cheng, YH and Chen, KE and Tsay, YF}, title = {Nitrate Transport, Signaling, and Use Efficiency.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {85-122}, doi = {10.1146/annurev-arplant-042817-040056}, pmid = {29570365}, issn = {1545-2123}, abstract = {Nitrogen accounts for approximately 60% of the fertilizer consumed each year; thus, it represents one of the major input costs for most nonlegume crops. Nitrate is one of the two major forms of nitrogen that plants acquire from the soil. Mechanistic insights into nitrate transport and signaling have enabled new strategies for enhancing nitrogen utilization efficiency, for lowering input costs for farming, and, more importantly, for alleviating environmental impacts (e.g., eutrophication and production of the greenhouse gas N2O). Over the past decade, significant progress has been made in understanding how nitrate is acquired from the surroundings, how it is efficiently distributed into different plant tissues in response to environmental changes, how nitrate signaling is perceived and transmitted, and how shoot and root nitrogen status is communicated. Several key components of these processes have proven to be novel tools for enhancing nitrate- and nitrogen-use efficiency. In this review, we focus on the roles of NRT1 and NRT2 in nitrate uptake and nitrate allocation among different tissues; we describe the functions of the transceptor NRT1.1, transcription factors, and small signaling peptides in nitrate signaling and tissue communication; and we compile the new strategies for improving nitrogen-use efficiency.}, } @article {pmid29570364, year = {2018}, author = {Strasser, R}, title = {Protein Quality Control in the Endoplasmic Reticulum of Plants.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {147-172}, doi = {10.1146/annurev-arplant-042817-040331}, pmid = {29570364}, issn = {1545-2123}, abstract = {The endoplasmic reticulum (ER) is the site of maturation for roughly one-third of all cellular proteins. ER-resident molecular chaperones and folding catalysts promote folding and assembly in a diverse set of newly synthesized proteins. Because these processes are error-prone, all eukaryotic cells have a quality-control system in place that constantly monitors the proteins and decides their fate. Proteins with potentially harmful nonnative conformations are subjected to assisted folding or degraded. Persistent folding-defective proteins are distinguished from folding intermediates and targeted for degradation by a specific process involving clearance from the ER. Although the basic principles of these processes appear conserved from yeast to animals and plants, there are distinct differences in the ER-associated degradation of misfolded glycoproteins. The general importance of ER quality-control events is underscored by their involvement in the biogenesis of diverse cell surface receptors and their crucial maintenance of protein homeostasis under diverse stress conditions.}, } @article {pmid29570352, year = {2018}, author = {Lin, J and Zhou, D and Steitz, TA and Polikanov, YS and Gagnon, MG}, title = {Ribosome-Targeting Antibiotics: Modes of Action, Mechanisms of Resistance, and Implications for Drug Design.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {451-478}, doi = {10.1146/annurev-biochem-062917-011942}, pmid = {29570352}, issn = {1545-4509}, abstract = {Genetic information is translated into proteins by the ribosome. Structural studies of the ribosome and of its complexes with factors and inhibitors have provided invaluable information on the mechanism of protein synthesis. Ribosome inhibitors are among the most successful antimicrobial drugs and constitute more than half of all medicines used to treat infections. However, bacterial infections are becoming increasingly difficult to treat because the microbes have developed resistance to the most effective antibiotics, creating a major public health care threat. This has spurred a renewed interest in structure-function studies of protein synthesis inhibitors, and in few cases, compounds have been developed into potent therapeutic agents against drug-resistant pathogens. In this review, we describe the modes of action of many ribosome-targeting antibiotics, highlight the major resistance mechanisms developed by pathogenic bacteria, and discuss recent advances in structure-assisted design of new molecules.}, } @article {pmid29569814, year = {2018}, author = {Xia, X and Huo, W and Wan, R and Wang, P and Zhang, L and Chang, Z}, title = {Molecular cloning, characterization, and expression profiles of the Sox3 gene in Chinese loach Paramisgurnus dabryanus.}, journal = {Evolution & development}, volume = {20}, number = {3-4}, pages = {108-118}, doi = {10.1111/ede.12252}, pmid = {29569814}, issn = {1525-142X}, mesh = {Animals ; Cloning, Molecular ; Cypriniformes/*embryology/*genetics ; Fish Proteins/chemistry/*genetics ; Phylogeny ; SOXB1 Transcription Factors/chemistry/*genetics ; Sequence Homology, Amino Acid ; Transcriptome ; }, abstract = {A number of studies have established that in vertebrates, Sox3 is involved in a wide range of developmental processes, including sex differentiation and neurogenesis. However, the exact functions of the Sox3 gene have not been documented so far in teleosts. Here, we cloned the full length cDNA of Sox3 from the teleost fish, Paramisgurnus dabryanus, which we designated PdSox3. Sequence analysis revealed that PdSox3 encodes a hydrophilic protein, and shares high homology with Sox3 in other species, ranging from mammals to fishes. Quantitative real-time reverse transcription PCR, and in situ hybridization showed that PdSox3 is consistently expressed during embryogenesis, mainly localized in the developing central nervous system. Tissue distribution analyses revealed that PdSox3 is abundant in the adult brain, especially in particle cell layer. Furthermore, PdSox3 expression was higher in gonads, in primary spermatocyte cells, primary oocytes, and previtellogenic oocyte cells. All of these results suggest that PdSox3 plays an important role in early embryonic development, in particular the formation and development of the nervous system, and gonad development, similarly to other vertebrates. This is the first report describing Sox3 gene expression from this species, and the results are necessary to provide fundamental information on both the functional and evolutionary role of Sox3 across different species.}, } @article {pmid29569309, year = {2018}, author = {Sato, Y and Sakamoto, H and Gotoh, T and Saito, Y and Chao, JT and Egas, M and Mochizuki, A}, title = {Patterns of reproductive isolation in a haplodiploid - strong post-mating, prezygotic barriers among three forms of a social spider mite.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {866-881}, doi = {10.1111/jeb.13270}, pmid = {29569309}, issn = {1420-9101}, abstract = {In speciation research, much attention is paid to the evolution of reproductive barriers, preventing diverging groups from hybridizing back into one gene pool. The prevalent view is that reproductive barriers evolve gradually as a by-product of genetic changes accumulated by natural selection and genetic drift in groups that are segregated spatially and/or temporally. Reproductive barriers, however, can also be reinforced by natural selection against maladaptive hybridization. These mutually compatible theories are both empirically supported by studies, analysing relationships between intensity of reproductive isolation and genetic distance in sympatric taxa and allopatric taxa. Here, we present the - to our knowledge - first comparative study in a haplodiploid organism, the social spider mite Stigmaeopsis miscanthi, by measuring premating and post-mating, pre- and post-zygotic components of reproductive isolation, using three recently diverged forms of the mite that partly overlap in home range. We carried out cross-experiments and measured genetic distances (mitochondrial DNA and nuclear DNA) among parapatric and allopatric populations of the three forms. Our results show that the three forms are reproductively isolated, despite the absence of premating barriers, and that the post-mating, prezygotic component contributes most to reproductive isolation. As expected, the strength of post-mating reproductive barriers positively correlated with genetic distance. We did not find a clear pattern of prezygotic barriers evolving faster in parapatry than in allopatry, although one form did show a trend in line with the ecological and behavioural relationships between the forms. Our study advocates the versatility of haplodiploid animals for investigating the evolution of reproductive barriers.}, } @article {pmid29569292, year = {2018}, author = {Höckerstedt, LM and Siren, JP and Laine, AL}, title = {Effect of spatial connectivity on host resistance in a highly fragmented natural pathosystem.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {844-852}, pmid = {29569292}, issn = {1420-9101}, abstract = {Both theory and experimental evolution studies predict migration to influence the outcome of antagonistic coevolution between hosts and their parasites, with higher migration rates leading to increased diversity and evolutionary potential. Migration rates are expected to vary in spatially structured natural pathosystems, yet how spatial structure generates variation in coevolutionary trajectories across populations occupying the same landscape has not been tested. Here, we studied the effect of spatial connectivity on host evolutionary potential in a natural pathosystem characterized by a stable Plantago lanceolata host network and a highly dynamic Podosphaera plantaginis parasite metapopulation. We designed a large inoculation experiment to test resistance of five isolated and five well-connected host populations against sympatric and allopatric pathogen strains, over 4 years. Contrary to our expectations, we did not find consistently higher resistance against sympatric pathogen strains in the well-connected populations. Instead, host local adaptation varied considerably among populations and through time with greater fluctuations observed in the well-connected populations. Jointly, our results suggest that in populations where pathogens have successfully established, they have the upper hand in the coevolutionary arms race, but hosts may be better able to respond to pathogen-imposed selection in the well-connected than in the isolated populations. Hence, the ongoing and extensive fragmentation of natural habitats may increase vulnerability to diseases.}, } @article {pmid29569290, year = {2018}, author = {Sniegula, S and Golab, MJ and Drobniak, SM and Johansson, F}, title = {The genetic variance but not the genetic covariance of life-history traits changes towards the north in a time-constrained insect.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {853-865}, doi = {10.1111/jeb.13269}, pmid = {29569290}, issn = {1420-9101}, abstract = {Seasonal time constraints are usually stronger at higher than lower latitudes and can exert strong selection on life-history traits and the correlations among these traits. To predict the response of life-history traits to environmental change along a latitudinal gradient, information must be obtained about genetic variance in traits and also genetic correlation between traits, that is the genetic variance-covariance matrix, G. Here, we estimated G for key life-history traits in an obligate univoltine damselfly that faces seasonal time constraints. We exposed populations to simulated native temperatures and photoperiods and common garden environmental conditions in a laboratory set-up. Despite differences in genetic variance in these traits between populations (lower variance at northern latitudes), there was no evidence for latitude-specific covariance of the life-history traits. At simulated native conditions, all populations showed strong genetic and phenotypic correlations between traits that shaped growth and development. The variance-covariance matrix changed considerably when populations were exposed to common garden conditions compared with the simulated natural conditions, showing the importance of environmentally induced changes in multivariate genetic structure. Our results highlight the importance of estimating variance-covariance matrixes in environments that mimic selection pressures and not only trait variances or mean trait values in common garden conditions for understanding the trait evolution across populations and environments.}, } @article {pmid29569154, year = {2018}, author = {Li, Y and Liu, X and Guo, H}, title = {Variations in Endosymbiont Infection Between Buprofezin-Resistant and Susceptible Strains of Laodelphax striatellus (Fallén).}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {709-715}, pmid = {29569154}, issn = {1432-0991}, support = {31672027//The National Natural Science Foundation of China/ ; cx(16)1001//The Independent Innovation Fund of Agricultural Science and Technology in Jiangsu province, China/ ; }, mesh = {Serratia/drug effects/metabolism/*physiology ; Thiadiazines/*pharmacology ; Wolbachia/drug effects/metabolism/*physiology ; }, abstract = {The endosymbionts Wolbachia and Rickettsia have been shown to be correlated with the insecticide resistance of mosquito and whitefly. The small brown planthopper (SBPH), Laodelphax striatellus, harbours many species of endosymbionts, and has developed a high resistance to buprofezin in China. In this study, we examined the species and the infection incidences of endosymbionts in a buprofezin-resistant (BR) strain, a buprofezin-susceptible (BS) strain, and the BR strain after exposure to buprofezin, and we also investigated the change in buprofezin susceptibility after removal of Wolbachia from the BR strain. The results showed that Wolbachia infection incidences were 100% in both the BR and BS strains, but the Wolbachia density in the BR strain was significantly higher than that in the BS strain. There were no significant differences in Arsenophonus infection incidence between the two strains. However, the infection incidence of Serratia and double infection incidence of Serratia + Wolbachia in the BR strain were significantly higher than that in the BS strain. After the BR strain was exposed to 1200 mg/L buprofezin, the infection incidence of Arsenophonus in the surviving individuals increased, and the infection rate of Serratia did not differ, but the double infection incidence of Serratia + Wolbachia decreased. And when a Wolbachia-infected line originating from the BR strain was cleared of Wolbachia, its susceptibility to buprofezin increased. The results suggest that Serratia and Wolbachia infection might improve the buprofezin resistance of SBPH.}, } @article {pmid29568218, year = {2018}, author = {Ren, S and Bertels, K and Al-Ars, Z}, title = {Efficient Acceleration of the Pair-HMMs Forward Algorithm for GATK HaplotypeCaller on Graphics Processing Units.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318760543}, pmid = {29568218}, issn = {1176-9343}, abstract = {GATK HaplotypeCaller (HC) is a popular variant caller, which is widely used to identify variants in complex genomes. However, due to its high variants detection accuracy, it suffers from long execution time. In GATK HC, the pair-HMMs forward algorithm accounts for a large percentage of the total execution time. This article proposes to accelerate the pair-HMMs forward algorithm on graphics processing units (GPUs) to improve the performance of GATK HC. This article presents several GPU-based implementations of the pair-HMMs forward algorithm. It also analyzes the performance bottlenecks of the implementations on an NVIDIA Tesla K40 card with various data sets. Based on these results and the characteristics of GATK HC, we are able to identify the GPU-based implementations with the highest performance for the various analyzed data sets. Experimental results show that the GPU-based implementations of the pair-HMMs forward algorithm achieve a speedup of up to 5.47× over existing GPU-based implementations.}, } @article {pmid29567867, year = {2018}, author = {Rai, TS and Valdesolo, P and Graham, J}, title = {Reply to Fincher et al.: Conceptual specificity in dehumanization research is a feature, not a bug.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3331-E3332}, pmid = {29567867}, issn = {1091-6490}, mesh = {*Dehumanization ; Research ; Sensitivity and Specificity ; }, } @article {pmid29567866, year = {2018}, author = {Zhang, T and Song, W and Li, Z and Qian, W and Wei, L and Yang, Y and Wang, W and Zhou, X and Meng, M and Peng, J and Xia, Q and Perrimon, N and Cheng, D}, title = {Krüppel homolog 1 represses insect ecdysone biosynthesis by directly inhibiting the transcription of steroidogenic enzymes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3960-3965}, pmid = {29567866}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Biosynthetic Pathways ; Bombyx/enzymology/genetics/growth & development/*metabolism ; DNA Methylation ; Drosophila/enzymology/genetics/growth & development/*metabolism ; Ecdysone/*biosynthesis ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Insect Proteins/genetics/*metabolism ; Juvenile Hormones/metabolism ; Kruppel-Like Transcription Factors/genetics/*metabolism ; Promoter Regions, Genetic ; Pupa ; }, abstract = {In insects, juvenile hormone (JH) and the steroid hormone ecdysone have opposing effects on regulation of the larval-pupal transition. Although increasing evidence suggests that JH represses ecdysone biosynthesis during larval development, the mechanism underlying this repression is not well understood. Here, we demonstrate that the expression of the Krüppel homolog 1 (Kr-h1), a gene encoding a transcription factor that mediates JH signaling, in ecdysone-producing organ prothoracic gland (PG) represses ecdysone biosynthesis by directly inhibiting the transcription of steroidogenic enzymes in both Drosophila and Bombyx Application of a JH mimic on ex vivo cultured PGs from Drosophila and Bombyx larvae induces Kr-h1 expression and inhibits the transcription of steroidogenic enzymes. In addition, PG-specific knockdown of Drosophila Kr-h1 promotes-while overexpression hampers-ecdysone production and pupariation. We further find that Kr-h1 inhibits the transcription of steroidogenic enzymes by directly binding to their promoters to induce promoter DNA methylation. Finally, we show that Kr-h1 does not affect DNA replication in Drosophila PG cells and that the reduction of PG size mediated by Kr-h1 overexpression can be rescued by feeding ecdysone. Taken together, our data indicate direct and conserved Kr-h1 repression of insect ecdysone biosynthesis in response to JH stimulation, providing insights into mechanisms underlying the antagonistic roles of JH and ecdysone.}, } @article {pmid29567810, year = {2018}, author = {Blättler, CL and Claire, MW and Prave, AR and Kirsimäe, K and Higgins, JA and Medvedev, PV and Romashkin, AE and Rychanchik, DV and Zerkle, AL and Paiste, K and Kreitsmann, T and Millar, IL and Hayles, JA and Bao, H and Turchyn, AV and Warke, MR and Lepland, A}, title = {Two-billion-year-old evaporites capture Earth's great oxidation.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {320-323}, doi = {10.1126/science.aar2687}, pmid = {29567810}, issn = {1095-9203}, abstract = {Major changes in atmospheric and ocean chemistry occurred in the Paleoproterozoic era (2.5 to 1.6 billion years ago). Increasing oxidation dramatically changed Earth's surface, but few quantitative constraints exist on this important transition. This study describes the sedimentology, mineralogy, and geochemistry of a 2-billion-year-old, ~800-meter-thick evaporite succession from the Onega Basin in Russian Karelia. The deposit consists of a basal unit dominated by halite (~100 meters) followed by units dominated by anhydrite-magnesite (~500 meters) and dolomite-magnesite (~200 meters). The evaporite minerals robustly constrain marine sulfate concentrations to at least 10 millimoles per kilogram of water, representing an oxidant reservoir equivalent to more than 20% of the modern ocean-atmosphere oxidizing capacity. These results show that substantial amounts of surface oxidant accumulated during this critical transition in Earth's oxygenation.}, } @article {pmid29567809, year = {2018}, author = {van Vugt, B and Dagnino, B and Vartak, D and Safaai, H and Panzeri, S and Dehaene, S and Roelfsema, PR}, title = {The threshold for conscious report: Signal loss and response bias in visual and frontal cortex.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {537-542}, doi = {10.1126/science.aar7186}, pmid = {29567809}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Animals ; Consciousness/*physiology ; Frontal Lobe/*physiology ; Macaca mulatta ; Male ; Models, Neurological ; Photic Stimulation ; Visual Cortex/*physiology ; Visual Perception/*physiology ; }, abstract = {Why are some visual stimuli consciously detected, whereas others remain subliminal? We investigated the fate of weak visual stimuli in the visual and frontal cortex of awake monkeys trained to report stimulus presence. Reported stimuli were associated with strong sustained activity in the frontal cortex, and frontal activity was weaker and quickly decayed for unreported stimuli. Information about weak stimuli could be lost at successive stages en route from the visual to the frontal cortex, and these propagation failures were confirmed through microstimulation of area V1. Fluctuations in response bias and sensitivity during perception of identical stimuli were traced back to prestimulus brain-state markers. A model in which stimuli become consciously reportable when they elicit a nonlinear ignition process in higher cortical areas explained our results.}, } @article {pmid29567808, year = {2018}, author = {Van Meter, KJ and Van Cappellen, P and Basu, NB}, title = {Legacy nitrogen may prevent achievement of water quality goals in the Gulf of Mexico.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {427-430}, doi = {10.1126/science.aar4462}, pmid = {29567808}, issn = {1095-9203}, abstract = {In August 2017, the Gulf of Mexico's hypoxic zone was declared to be the largest ever measured. It has been estimated that a 60% decrease in watershed nitrogen (N) loading may be necessary to adequately reduce eutrophication in the Gulf. However, to date there has been no rigorous assessment of the effect of N legacies on achieving water quality goals. In this study, we show that even if agricultural N use became 100% efficient, it would take decades to meet target N loads due to legacy N within the Mississippi River basin. Our results suggest that both long-term commitment and large-scale changes in agricultural management practices will be necessary to decrease Mississippi N loads and to meet current goals for reducing the size of the Gulf hypoxic zone.}, } @article {pmid29567807, year = {2018}, author = {Kobayashi, K and Jomaa, A and Lee, JH and Chandrasekar, S and Boehringer, D and Shan, SO and Ban, N}, title = {Structure of a prehandover mammalian ribosomal SRP·SRP receptor targeting complex.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {323-327}, doi = {10.1126/science.aar7924}, pmid = {29567807}, issn = {1095-9203}, support = {R01 GM078024/GM/NIGMS NIH HHS/United States ; R01 GM107368/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cryoelectron Microscopy ; GTP Phosphohydrolases/chemistry ; Guanosine Triphosphate/chemistry ; Hydrolysis ; Protein Conformation ; Protein Multimerization ; *Protein Sorting Signals ; RNA/chemistry ; Receptors, Cytoplasmic and Nuclear/*chemistry/ultrastructure ; Receptors, Peptide/*chemistry/ultrastructure ; Ribosomes/*chemistry/ultrastructure ; }, abstract = {Signal recognition particle (SRP) targets proteins to the endoplasmic reticulum (ER). SRP recognizes the ribosome synthesizing a signal sequence and delivers it to the SRP receptor (SR) on the ER membrane followed by the transfer of the signal sequence to the translocon. Here, we present the cryo-electron microscopy structure of the mammalian translating ribosome in complex with SRP and SR in a conformation preceding signal sequence handover. The structure visualizes all eukaryotic-specific SRP and SR proteins and reveals their roles in stabilizing this conformation by forming a large protein assembly at the distal site of SRP RNA. We provide biochemical evidence that the guanosine triphosphate hydrolysis of SRP·SR is delayed at this stage, possibly to provide a time window for signal sequence handover to the translocon.}, } @article {pmid29567717, year = {2018}, author = {Topalidou, I}, title = {The freedom of choice.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1434}, doi = {10.1126/science.359.6382.1434}, pmid = {29567717}, issn = {1095-9203}, } @article {pmid29567716, year = {2018}, author = {Terenzio, M and Koley, S and Samra, N and Rishal, I and Zhao, Q and Sahoo, PK and Urisman, A and Marvaldi, L and Oses-Prieto, JA and Forester, C and Gomes, C and Kalinski, AL and Di Pizio, A and Doron-Mandel, E and Perry, RB and Koppel, I and Twiss, JL and Burlingame, AL and Fainzilber, M}, title = {Locally translated mTOR controls axonal local translation in nerve injury.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1416-1421}, doi = {10.1126/science.aan1053}, pmid = {29567716}, issn = {1095-9203}, support = {P41 GM103481/GM/NIGMS NIH HHS/United States ; R01 NS041596/NS/NINDS NIH HHS/United States ; R01 NS089633/NS/NINDS NIH HHS/United States ; }, mesh = {3' Untranslated Regions ; Animals ; Axons/*metabolism ; Cell Size ; Ganglia, Spinal/*injuries ; Mice ; Mice, Inbred Strains ; Phosphoproteins/metabolism ; *Protein Biosynthesis ; RNA, Messenger/metabolism ; RNA-Binding Proteins/metabolism ; Rats ; Rats, Inbred BB ; Rats, Sprague-Dawley ; Sciatic Nerve/*injuries ; Signal Transduction ; TOR Serine-Threonine Kinases/*biosynthesis/genetics ; }, abstract = {How is protein synthesis initiated locally in neurons? We found that mTOR (mechanistic target of rapamycin) was activated and then up-regulated in injured axons, owing to local translation of mTOR messenger RNA (mRNA). This mRNA was transported into axons by the cell size-regulating RNA-binding protein nucleolin. Furthermore, mTOR controlled local translation in injured axons. This included regulation of its own translation and that of retrograde injury signaling molecules such as importin β1 and STAT3 (signal transducer and activator of transcription 3). Deletion of the mTOR 3' untranslated region (3'UTR) in mice reduced mTOR in axons and decreased local translation after nerve injury. Both pharmacological inhibition of mTOR in axons and deletion of the mTOR 3'UTR decreased proprioceptive neuronal survival after nerve injury. Thus, mRNA localization enables spatiotemporal control of mTOR pathways regulating local translation and long-range intracellular signaling.}, } @article {pmid29567715, year = {2018}, author = {Kenney, GE and Dassama, LMK and Pandelia, ME and Gizzi, AS and Martinie, RJ and Gao, P and DeHart, CJ and Schachner, LF and Skinner, OS and Ro, SY and Zhu, X and Sadek, M and Thomas, PM and Almo, SC and Bollinger, JM and Krebs, C and Kelleher, NL and Rosenzweig, AC}, title = {The biosynthesis of methanobactin.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1411-1416}, pmid = {29567715}, issn = {1095-9203}, support = {P01 GM118303/GM/NIGMS NIH HHS/United States ; R35 GM118035/GM/NIGMS NIH HHS/United States ; R01 AT009143/AT/NCCIH NIH HHS/United States ; F32 GM110934/GM/NIGMS NIH HHS/United States ; P41 GM108569/GM/NIGMS NIH HHS/United States ; T32 GM105538/GM/NIGMS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; U54 GM093342/GM/NIGMS NIH HHS/United States ; U54 GM094662/GM/NIGMS NIH HHS/United States ; R00 GM111978/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Copper/*metabolism ; Genome, Bacterial ; Imidazoles/chemistry/metabolism ; Ligands ; Methylosinus trichosporium/genetics/*metabolism ; Oligopeptides/*biosynthesis/chemistry/genetics/metabolism ; Oxidation-Reduction ; Oxygen/metabolism ; Protein Conformation, alpha-Helical ; Protein Multimerization ; *Protein Processing, Post-Translational ; }, abstract = {Metal homeostasis poses a major challenge to microbes, which must acquire scarce elements for core metabolic processes. Methanobactin, an extensively modified copper-chelating peptide, was one of the earliest natural products shown to enable microbial acquisition of a metal other than iron. We describe the core biosynthetic machinery responsible for the characteristic posttranslational modifications that grant methanobactin its specificity and affinity for copper. A heterodimer comprising MbnB, a DUF692 family iron enzyme, and MbnC, a protein from a previously unknown family, performs a dioxygen-dependent four-electron oxidation of the precursor peptide (MbnA) to install an oxazolone and an adjacent thioamide, the characteristic methanobactin bidentate copper ligands. MbnB and MbnC homologs are encoded together and separately in many bacterial genomes, suggesting functions beyond their roles in methanobactin biosynthesis.}, } @article {pmid29567714, year = {2018}, author = {Brown, M and Assen, FP and Leithner, A and Abe, J and Schachner, H and Asfour, G and Bago-Horvath, Z and Stein, JV and Uhrin, P and Sixt, M and Kerjaschki, D}, title = {Lymph node blood vessels provide exit routes for metastatic tumor cell dissemination in mice.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1408-1411}, doi = {10.1126/science.aal3662}, pmid = {29567714}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Animals ; Blood Vessels/*pathology ; Cell Line, Tumor ; Female ; Humans ; Lung/pathology ; Lymph Nodes/*blood supply/*pathology ; Lymphatic Metastasis/*pathology ; Mammary Neoplasms, Experimental ; Mice ; *Neoplasm Seeding ; Neoplasms, Experimental ; Neoplastic Cells, Circulating/*pathology ; Thoracic Duct/pathology ; }, abstract = {During metastasis, malignant cells escape the primary tumor, intravasate lymphatic vessels, and reach draining sentinel lymph nodes before they colonize distant organs via the blood circulation. Although lymph node metastasis in cancer patients correlates with poor prognosis, evidence is lacking as to whether and how tumor cells enter the bloodstream via lymph nodes. To investigate this question, we delivered carcinoma cells into the lymph nodes of mice by microinfusing the cells into afferent lymphatic vessels. We found that tumor cells rapidly infiltrated the lymph node parenchyma, invaded blood vessels, and seeded lung metastases without involvement of the thoracic duct. These results suggest that the lymph node blood vessels can serve as an exit route for systemic dissemination of cancer cells in experimental mouse models. Whether this form of tumor cell spreading occurs in cancer patients remains to be determined.}, } @article {pmid29567713, year = {2018}, author = {Pereira, ER and Kedrin, D and Seano, G and Gautier, O and Meijer, EFJ and Jones, D and Chin, SM and Kitahara, S and Bouta, EM and Chang, J and Beech, E and Jeong, HS and Carroll, MC and Taghian, AG and Padera, TP}, title = {Lymph node metastases can invade local blood vessels, exit the node, and colonize distant organs in mice.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1403-1407}, pmid = {29567713}, issn = {1095-9203}, support = {T32 DK007191/DK/NIDDK NIH HHS/United States ; C06 CA059267/CA/NCI NIH HHS/United States ; R01 CA214913/CA/NCI NIH HHS/United States ; P01 CA080124/CA/NCI NIH HHS/United States ; DP2 OD008780/OD/NIH HHS/United States ; UL1 TR001102/TR/NCATS NIH HHS/United States ; R01 HL128168/HL/NHLBI NIH HHS/United States ; F32 CA183465/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Blood Vessels/*pathology ; Carcinoma, Squamous Cell ; Cell Line, Tumor ; Cell Movement ; Cell Tracking/methods ; Cytosol/chemistry ; Female ; Luminescent Proteins/analysis ; Lung/pathology ; Lymph Nodes/*pathology ; Lymphatic Metastasis/*pathology ; Melanoma, Experimental ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; *Neoplasm Seeding ; Neoplastic Cells, Circulating ; }, abstract = {Lymph node metastases in cancer patients are associated with tumor aggressiveness, poorer prognoses, and the recommendation for systemic therapy. Whether cancer cells in lymph nodes can seed distant metastases has been a subject of considerable debate. We studied mice implanted with cancer cells (mammary carcinoma, squamous cell carcinoma, or melanoma) expressing the photoconvertible protein Dendra2. This technology allowed us to selectively photoconvert metastatic cells in the lymph node and trace their fate. We found that a fraction of these cells invaded lymph node blood vessels, entered the blood circulation, and colonized the lung. Thus, in mouse models, lymph node metastases can be a source of cancer cells for distant metastases. Whether this mode of dissemination occurs in cancer patients remains to be determined.}, } @article {pmid29567712, year = {2018}, author = {Sakulkoo, W and Osés-Ruiz, M and Oliveira Garcia, E and Soanes, DM and Littlejohn, GR and Hacker, C and Correia, A and Valent, B and Talbot, NJ}, title = {A single fungal MAP kinase controls plant cell-to-cell invasion by the rice blast fungus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1399-1403}, doi = {10.1126/science.aaq0892}, pmid = {29567712}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Disease Resistance ; *Host-Pathogen Interactions ; Hyphae/enzymology/genetics/growth & development/pathogenicity ; Magnaporthe/*enzymology/genetics/growth & development/*pathogenicity ; Mitogen-Activated Protein Kinases/genetics/*physiology ; Oryza/immunology/*microbiology ; Plant Cells/microbiology ; Plant Diseases/*microbiology ; }, abstract = {Blast disease destroys up to 30% of the rice crop annually and threatens global food security. The blast fungus Magnaporthe oryzae invades plant tissue with hyphae that proliferate and grow from cell to cell, often through pit fields, where plasmodesmata cluster. We showed that chemical genetic inhibition of a single fungal mitogen-activated protein (MAP) kinase, Pmk1, prevents M. oryzae from infecting adjacent plant cells, leaving the fungus trapped within a single plant cell. Pmk1 regulates expression of secreted fungal effector proteins implicated in suppression of host immune defenses, preventing reactive oxygen species generation and excessive callose deposition at plasmodesmata. Furthermore, Pmk1 controls the hyphal constriction required for fungal growth from one rice cell to the neighboring cell, enabling host tissue colonization and blast disease.}, } @article {pmid29567711, year = {2018}, author = {Bedrosian, TA and Quayle, C and Novaresi, N and Gage, FH}, title = {Early life experience drives structural variation of neural genomes in mice.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1395-1399}, doi = {10.1126/science.aah3378}, pmid = {29567711}, issn = {1095-9203}, support = {R01 MH095741/MH/NIMH NIH HHS/United States ; U01 MH106882/MH/NIMH NIH HHS/United States ; F32 MH102983/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Binding Sites/genetics ; *DNA Copy Number Variations ; *DNA Methylation ; *Epigenesis, Genetic ; Hippocampus/*growth & development ; *Long Interspersed Nucleotide Elements ; *Maternal Behavior ; Mice ; *Mosaicism ; Neurogenesis/*genetics ; Polymerase Chain Reaction ; YY1 Transcription Factor/metabolism ; }, abstract = {The brain is a genomic mosaic owing to somatic mutations that arise throughout development. Mobile genetic elements, including retrotransposons, are one source of somatic mosaicism in the brain. Retrotransposition may represent a form of plasticity in response to experience. Here, we use droplet digital polymerase chain reaction to show that natural variations in maternal care mediate the mobilization of long interspersed nuclear element-1 (LINE-1 or L1) retrotransposons in the hippocampus of the mouse brain. Increasing the amount of maternal care blocks the accumulation of L1. Maternal care also alters DNA methylation at YY1 binding sites implicated in L1 activation and affects expression of the de novo methyltransferase DNMT3a. Our observations indicate that early life experience drives somatic variation in the genome via L1 retrotransposons.}, } @article {pmid29567710, year = {2018}, author = {Joo, Y and Agarkar, V and Sung, SH and Savoie, BM and Boudouris, BW}, title = {A nonconjugated radical polymer glass with high electrical conductivity.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1391-1395}, doi = {10.1126/science.aao7287}, pmid = {29567710}, issn = {1095-9203}, abstract = {Solid-state conducting polymers usually have highly conjugated macromolecular backbones and require intentional doping in order to achieve high electrical conductivities. Conversely, single-component, charge-neutral macromolecules could be synthetically simpler and have improved processibility and ambient stability. We show that poly(4-glycidyloxy-2,2,6,6-tetramethylpiperidine-1-oxyl), a nonconjugated radical polymer with a subambient glass transition temperature, underwent rapid solid-state charge transfer reactions and had an electrical conductivity of up to 28 siemens per meter over channel lengths up to 0.6 micrometers. The charge transport through the radical polymer film was enabled with thermal annealing at 80°C, which allowed for the formation of a percolating network of open-shell sites in electronic communication with one another. The electrical conductivity was not enhanced by intentional doping, and thin films of this material showed high optical transparency.}, } @article {pmid29567709, year = {2018}, author = {Faber, JA and Arrieta, AF and Studart, AR}, title = {Bioinspired spring origami.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1386-1391}, doi = {10.1126/science.aap7753}, pmid = {29567709}, issn = {1095-9203}, abstract = {Origami enables folding of objects into a variety of shapes in arts, engineering, and biological systems. In contrast to well-known paper-folded objects, the wing of the earwig has an exquisite natural folding system that cannot be sufficiently described by current origami models. Such an unusual biological system displays incompatible folding patterns, remains open by a bistable locking mechanism during flight, and self-folds rapidly without muscular actuation. We show that these notable functionalities arise from the protein-rich joints of the earwig wing, which work as extensional and rotational springs between facets. Inspired by this biological wing, we establish a spring origami model that broadens the folding design space of traditional origami and allows for the fabrication of precisely tunable, four-dimensional-printed objects with programmable bioinspired morphing functionalities.}, } @article {pmid29567708, year = {2018}, author = {Zitvogel, L and Ma, Y and Raoult, D and Kroemer, G and Gajewski, TF}, title = {The microbiome in cancer immunotherapy: Diagnostic tools and therapeutic strategies.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1366-1370}, doi = {10.1126/science.aar6918}, pmid = {29567708}, issn = {1095-9203}, mesh = {*Gastrointestinal Microbiome/genetics ; Humans ; Immune System ; Immunotherapy/*methods ; Metagenome ; Neoplasms/diagnosis/*microbiology/*therapy ; Treatment Outcome ; }, abstract = {The fine line between human health and disease can be driven by the interplay between host and microbial factors. This "metagenome" regulates cancer initiation, progression, and response to therapies. Besides the capacity of distinct microbial species to modulate the pharmacodynamics of chemotherapeutic drugs, symbiosis between epithelial barriers and their microbial ecosystems has a major impact on the local and distant immune system, markedly influencing clinical outcome in cancer patients. Efficacy of cancer immunotherapy with immune checkpoint antibodies can be diminished with administration of antibiotics, and superior efficacy is observed with the presence of specific gut microbes. Future strategies of precision medicine will likely rely on novel diagnostic and therapeutic tools with which to identify and correct defects in the microbiome that compromise therapeutic efficacy.}, } @article {pmid29567707, year = {2018}, author = {June, CH and O'Connor, RS and Kawalekar, OU and Ghassemi, S and Milone, MC}, title = {CAR T cell immunotherapy for human cancer.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1361-1365}, doi = {10.1126/science.aar6711}, pmid = {29567707}, issn = {1095-9203}, support = {R01 CA226983/CA/NCI NIH HHS/United States ; R01 CA165206/CA/NCI NIH HHS/United States ; P01 CA214278/CA/NCI NIH HHS/United States ; }, mesh = {Cell Engineering/*methods ; Cell- and Tissue-Based Therapy ; Clinical Trials as Topic ; Genetic Engineering ; Humans ; Immunotherapy, Adoptive/*methods ; Mutant Chimeric Proteins/genetics/*immunology ; Neoplasms/*therapy ; Receptors, Antigen, T-Cell/genetics/*immunology ; T-Lymphocytes/*immunology/*transplantation ; }, abstract = {Adoptive T cell transfer (ACT) is a new area of transfusion medicine involving the infusion of lymphocytes to mediate antitumor, antiviral, or anti-inflammatory effects. The field has rapidly advanced from a promising form of immuno-oncology in preclinical models to the recent commercial approvals of chimeric antigen receptor (CAR) T cells to treat leukemia and lymphoma. This Review describes opportunities and challenges for entering mainstream oncology that presently face the CAR T field, with a focus on the challenges that have emerged over the past several years.}, } @article {pmid29567706, year = {2018}, author = {Sahin, U and Türeci, Ö}, title = {Personalized vaccines for cancer immunotherapy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1355-1360}, doi = {10.1126/science.aar7112}, pmid = {29567706}, issn = {1095-9203}, mesh = {Antigens, Neoplasm/genetics/immunology ; Cancer Vaccines/*genetics/*therapeutic use ; Humans ; Immunodominant Epitopes/genetics/immunology ; Immunotherapy/*methods ; Mutation ; Neoplasms/*genetics/*therapy ; Precision Medicine/*methods ; }, abstract = {Cancer is characterized by an accumulation of genetic alterations. Somatic mutations can generate cancer-specific neoepitopes that are recognized by autologous T cells as foreign and constitute ideal cancer vaccine targets. Every tumor has its own unique composition of mutations, with only a small fraction shared between patients. Technological advances in genomics, data science, and cancer immunotherapy now enable the rapid mapping of the mutations within a genome, rational selection of vaccine targets, and on-demand production of a therapy customized to a patient's individual tumor. First-in-human clinical trials of personalized cancer vaccines have shown the feasibility, safety, and immunotherapeutic activity of targeting individual tumor mutation signatures. With vaccination development being promoted by emerging innovations of the digital age, vaccinating a patient with individual tumor mutations may become the first truly personalized treatment for cancer.}, } @article {pmid29567705, year = {2018}, author = {Ribas, A and Wolchok, JD}, title = {Cancer immunotherapy using checkpoint blockade.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1350-1355}, doi = {10.1126/science.aar4060}, pmid = {29567705}, issn = {1095-9203}, support = {R35 CA197633/CA/NCI NIH HHS/United States ; P01 CA168585/CA/NCI NIH HHS/United States ; P30 CA016042/CA/NCI NIH HHS/United States ; R01 CA056821/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Antibodies/*therapeutic use ; CTLA-4 Antigen/*antagonists & inhibitors ; Humans ; Immunotherapy/*methods ; Neoplasms/*therapy ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; }, abstract = {The release of negative regulators of immune activation (immune checkpoints) that limit antitumor responses has resulted in unprecedented rates of long-lasting tumor responses in patients with a variety of cancers. This can be achieved by antibodies blocking the cytotoxic T lymphocyte-associated protein 4 (CTLA-4) or the programmed cell death 1 (PD-1) pathway, either alone or in combination. The main premise for inducing an immune response is the preexistence of antitumor T cells that were limited by specific immune checkpoints. Most patients who have tumor responses maintain long-lasting disease control, yet one-third of patients relapse. Mechanisms of acquired resistance are currently poorly understood, but evidence points to alterations that converge on the antigen presentation and interferon-γ signaling pathways. New-generation combinatorial therapies may overcome resistance mechanisms to immune checkpoint therapy.}, } @article {pmid29567704, year = {2018}, author = {Couzin-Frankel, J}, title = {Sticker shock.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1348-1349}, doi = {10.1126/science.359.6382.1348}, pmid = {29567704}, issn = {1095-9203}, mesh = {Antineoplastic Agents/*economics/therapeutic use ; Fees, Pharmaceutical/*trends ; Humans ; Immunotherapy/economics/trends ; Neoplasms/*drug therapy ; }, } @article {pmid29567703, year = {2018}, author = {Kaiser, J}, title = {Too much of a good thing?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1346-1347}, doi = {10.1126/science.359.6382.1346}, pmid = {29567703}, issn = {1095-9203}, mesh = {Clinical Trials as Topic ; Humans ; Immunotherapy/*methods ; Neoplasms/*therapy ; }, } @article {pmid29567702, year = {2018}, author = {Kelly, PN}, title = {The Cancer Immunotherapy Revolution.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1344-1345}, doi = {10.1126/science.359.6382.1344}, pmid = {29567702}, issn = {1095-9203}, mesh = {Humans ; Immunotherapy/*trends ; Neoplasms/*therapy ; }, } @article {pmid29567700, year = {2018}, author = {Rajput, ASD}, title = {India's Ph.D. scholar outreach requirement.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1343}, doi = {10.1126/science.aat0303}, pmid = {29567700}, issn = {1095-9203}, } @article {pmid29567699, year = {2018}, author = {Amir, AA}, title = {Mitigate risk for Malaysia's mangroves.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1342-1343}, doi = {10.1126/science.aas9139}, pmid = {29567699}, issn = {1095-9203}, mesh = {*Conservation of Natural Resources ; Malaysia ; Risk ; *Wetlands ; }, } @article {pmid29567698, year = {2018}, author = {Sims, DW and Mucientes, G and Queiroz, N}, title = {Shortfin mako sharks threatened by inaction.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1342}, doi = {10.1126/science.aat0315}, pmid = {29567698}, issn = {1095-9203}, mesh = {Animals ; *Endangered Species ; *Sharks ; }, } @article {pmid29567697, year = {2018}, author = {Dye, C}, title = {Expanded health systems for sustainable development.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1337-1339}, doi = {10.1126/science.aaq1081}, pmid = {29567697}, issn = {1095-9203}, support = {001//World Health Organization/International ; }, mesh = {*Conservation of Natural Resources ; *Delivery of Health Care ; *Economic Development ; Humans ; }, } @article {pmid29567696, year = {2018}, author = {Li, X and Carmeliet, P}, title = {Targeting angiogenic metabolism in disease.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1335-1336}, doi = {10.1126/science.aar5557}, pmid = {29567696}, issn = {1095-9203}, mesh = {Angiogenesis Inhibitors/pharmacology/*therapeutic use ; Animals ; Blood Vessels/drug effects ; Endothelial Cells/*drug effects/metabolism ; Glycolysis/drug effects ; Humans ; Metabolic Networks and Pathways/drug effects ; Mice ; Neoplasms/*blood supply/*drug therapy ; Neovascularization, Pathologic/*drug therapy/*metabolism ; }, } @article {pmid29567695, year = {2018}, author = {Lutkenhaus, J}, title = {A radical advance for conducting polymers.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1334-1335}, doi = {10.1126/science.aat1298}, pmid = {29567695}, issn = {1095-9203}, mesh = {*Electric Conductivity ; Nanotubes ; *Polymers ; }, } @article {pmid29567694, year = {2018}, author = {Protasiewicz, JD}, title = {From rock-stable to reactive phosphorus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1333}, doi = {10.1126/science.aat1206}, pmid = {29567694}, issn = {1095-9203}, mesh = {Phosphates/analysis ; *Phosphorus ; *Soil ; }, } @article {pmid29567693, year = {2018}, author = {Riccio, A}, title = {RNA targeting and translation in axons.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1331-1332}, doi = {10.1126/science.aat1498}, pmid = {29567693}, issn = {1095-9203}, mesh = {*Axons ; Humans ; Protein Biosynthesis ; *RNA ; }, } @article {pmid29567692, year = {2018}, author = {Song, S and Gleeson, JG}, title = {Early life experience shapes neural genome.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1330-1331}, doi = {10.1126/science.aat3977}, pmid = {29567692}, issn = {1095-9203}, mesh = {*Brain ; *Genome ; Humans ; }, } @article {pmid29567691, year = {2018}, author = {Schlesinger, WH}, title = {Are wood pellets a green fuel?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1328-1329}, doi = {10.1126/science.aat2305}, pmid = {29567691}, issn = {1095-9203}, } @article {pmid29567690, year = {2018}, author = {Voosen, P}, title = {The realist.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1320-1324}, doi = {10.1126/science.359.6382.1320}, pmid = {29567690}, issn = {1095-9203}, } @article {pmid29567689, year = {2018}, author = {Stokstad, E}, title = {A research behemoth is born in Britain.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1319}, doi = {10.1126/science.359.6382.1319}, pmid = {29567689}, issn = {1095-9203}, } @article {pmid29567688, year = {2018}, author = {Dengler, R}, title = {Protein may explain morning sickness, and worse.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1318}, doi = {10.1126/science.359.6382.1318}, pmid = {29567688}, issn = {1095-9203}, mesh = {Female ; Growth Differentiation Factor 15/antagonists & inhibitors/*metabolism ; Humans ; Hyperemesis Gravidarum/drug therapy/*metabolism ; Nausea/drug therapy/*metabolism ; Pregnancy ; }, } @article {pmid29567687, year = {2018}, author = {Clery, D}, title = {Stephen Hawking, betting man.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1317}, doi = {10.1126/science.359.6382.1317}, pmid = {29567687}, issn = {1095-9203}, } @article {pmid29567686, year = {2018}, author = {Cho, A}, title = {Hawking's bid to save quantum theory from black holes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1316-1317}, doi = {10.1126/science.359.6382.1316}, pmid = {29567686}, issn = {1095-9203}, } @article {pmid29567685, year = {2018}, author = {Rabesandratana, T}, title = {Accounting rules hobble Spanish institutes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1315-1316}, doi = {10.1126/science.359.6382.1315}, pmid = {29567685}, issn = {1095-9203}, } @article {pmid29567684, year = {2018}, author = {Stone, R}, title = {U.K. attack puts nerve agent in the spotlight.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1314-1315}, doi = {10.1126/science.359.6382.1314}, pmid = {29567684}, issn = {1095-9203}, mesh = {Acetylcholinesterase/*chemistry ; Chemical Warfare Agents/*chemistry/toxicity ; Cholinesterase Inhibitors/*chemistry/toxicity ; Humans ; Models, Chemical ; Nerve Agents/*chemistry/toxicity ; United Kingdom ; }, } @article {pmid29567683, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1310-1312}, doi = {10.1126/science.359.6382.1310}, pmid = {29567683}, issn = {1095-9203}, } @article {pmid29567682, year = {2018}, author = {Berg, J}, title = {Lumping and splitting.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1309}, doi = {10.1126/science.aat5956}, pmid = {29567682}, issn = {1095-9203}, } @article {pmid29567646, year = {2018}, author = {Fincher, KM and Kteily, NS and Bruneau, EG}, title = {Our humanity contains multitudes: Dehumanization is more than overlooking mental capacities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3329-E3330}, pmid = {29567646}, issn = {1091-6490}, mesh = {*Aggression ; *Dehumanization ; }, } @article {pmid29567588, year = {2018}, author = {Aulner, N and Danckaert, A and Fernandes, J and Nicola, MA and Roux, P and Salles, A and Tinevez, JY and Shorte, SL}, title = {Fluorescence imaging host pathogen interactions: fifteen years benefit of hindsight….}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {193-198}, doi = {10.1016/j.mib.2018.03.001}, pmid = {29567588}, issn = {1879-0364}, mesh = {Automation, Laboratory ; Containment of Biohazards ; *Host-Pathogen Interactions ; Humans ; Laboratories/organization & administration ; Microscopy, Fluorescence/instrumentation/*methods ; Molecular Imaging/instrumentation/methods ; }, abstract = {We consider in review current state-of-the-art fluorescence microscopy for investigating the host-pathogen interface. Our perspective is honed from years with literally thousands of microbiologists using the variety of imaging technologies available within our dedicated BSL2/BSL3 optical imaging research service facilities at the Institut Pasteur Paris founded from scratch in 2001. During fifteen years learning from the success and failures of introducing different fluorescence imaging technologies, methods, and technical development strategies we provide here a synopsis review of our experience to date and a synthesis of how we see the future in perspective for fluorescence imaging at the host-pathogen interface.}, } @article {pmid29567506, year = {2018}, author = {Silva, TFD and Schneider, H and Sampaio, I and Angulo, A and Brito, MFG and Santos, ACA and de Andrade Santos, J and Carvalho-Filho, A and Santos, S}, title = {Phylogeny of the subfamily Stelliferinae suggests speciation in Ophioscion Gill, 1863 (Sciaenidae: Perciformes) in the western South Atlantic.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {51-61}, doi = {10.1016/j.ympev.2018.03.025}, pmid = {29567506}, issn = {1095-9513}, mesh = {Animals ; Atlantic Ocean ; Bayes Theorem ; DNA, Mitochondrial/genetics ; *Genetic Speciation ; Genetic Variation ; Genome ; Panama ; Perciformes/*classification/*genetics ; *Phylogeny ; Phylogeography ; Species Specificity ; Time Factors ; }, abstract = {Phylogenies based on morphological and molecular data confirm the monophyly of the subfamily Stelliferinae; however, there is no consensus on the intergeneric and interspecific relationships in the group. Previous studies suggested the non-monophyly of Ophioscion and Stellifer, and possible cryptic species in Ophioscion punctatissimus. Therefore, we used mitochondrial (16S rDNA and COI) and nuclear (Rhodopsin, EGR1, and RAG1) regions to examine phylogenetic relationships among species of this subfamily. Our results confirmed the monophyly of Stelliferinae and supports the close relationship among Bardiella, Corvula and Odontoscion, which form a sister group to Stellifer and Ophioscion. Notwithstanding, all the results support the non-monophyly of Stellifer and Ophioscion and we suggest that a taxonomic revision should consider Ophioscion as a junior synonym of Stellifer. Moreover, O. punctatissimus was grouped into two clades, with the O. punctatissimus lineage I (LI) being closer to O. scierus from the eastern Pacific than to the O. punctatissimus lineage II (LII). The most recent common ancestor (TMRCA) for the O. scierus and O. punctatissimus LI and O. punctatissimus LII clade dates from 7.2 (HPD: 4.3-10.5) Ma, whereas TMRCA for the O. scierus and O. punctatissimus LI clade dates from 5.3 (HPD: 2.4-8.6) Ma, indicating that speciation processes may be related to the rise of the Isthmus of Panama. Phylogeographic analyses corroborate the hypothesis of speciation in O. punctatissimus. These results suggest that lineages of O. punctatissimus originated from distinct ancestors and, by morphological similarity, were considered the same taxon. A taxonomic revision should be performed to validate the species status of such lineages.}, } @article {pmid29567505, year = {2018}, author = {O'Connell, KA and Smith, EN}, title = {The effect of missing data on coalescent species delimitation and a taxonomic revision of whipsnakes (Colubridae: Masticophis).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {356-366}, doi = {10.1016/j.ympev.2018.03.018}, pmid = {29567505}, issn = {1095-9513}, abstract = {A stable alpha taxonomy is essential to understanding evolutionary processes and achieving effective conservation aims. Taxonomy depends on the identification of independently evolving lineages, and the delimitation of these lineages based on multiple lines of evidence. Coalescent species delimitation within an integrative framework has increased the rigor of the delimitation process. Here we use genome-wide SNP data and coalescent species delimitation to explore lineage relationships within several North American whipsnake species, test the species status of several lineages, and test the effect of missing data on species delimitation. We find support for the elevation of several previously recognized subspecies to full species status, and formally elevate two species. This study demonstrates the power of molecular data and model-based delimitation methods to identify evolutionary relationships, and finds that missing data have little impact on the outcome of delimitation analyses.}, } @article {pmid29567336, year = {2018}, author = {McGinty, RJ and Mirkin, SM}, title = {Cis- and Trans-Modifiers of Repeat Expansions: Blending Model Systems with Human Genetics.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {6}, pages = {448-465}, pmid = {29567336}, issn = {0168-9525}, support = {P01 GM105473/GM/NIGMS NIH HHS/United States ; R01 GM060987/GM/NIGMS NIH HHS/United States ; }, abstract = {Over 30 hereditary diseases are caused by the expansion of microsatellite repeats. The length of the expandable repeat is the main hereditary determinant of these disorders. They are also affected by numerous genomic variants that are either nearby (cis) or physically separated from (trans) the repetitive locus, which we review here. These genetic variants have largely been elucidated in model systems using gene knockouts, while a few have been directly observed as single-nucleotide polymorphisms (SNPs) in patients. There is a notable disconnect between these two bodies of knowledge: knockouts poorly approximate the SNP-level variation in human populations that gives rise to medically relevant cis- and trans-modifiers, while the rarity of these diseases limits the statistical power of SNP-based analysis in humans. We propose that high-throughput SNP-based screening in model systems could become a useful approach to quickly identify and characterize modifiers of clinical relevance for patients.}, } @article {pmid29567298, year = {2018}, author = {Stensvold, CR and van der Giezen, M}, title = {Associations between Gut Microbiota and Common Luminal Intestinal Parasites.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {369-377}, doi = {10.1016/j.pt.2018.02.004}, pmid = {29567298}, issn = {1471-5007}, mesh = {Blastocystis/*physiology ; Dientamoeba/*physiology ; *Environmental Biomarkers ; Gastrointestinal Microbiome/*physiology ; Host-Parasite Interactions/*physiology ; Humans ; Intestinal Diseases, Parasitic/*microbiology ; Intestines/microbiology/parasitology ; }, abstract = {The development and integration of DNA-based methods in research and clinical microbiology laboratories have enabled standardised and comprehensive detection and differentiation of the microbes colonising our guts. For instance, the single-celled parasites Blastocystis and Dientamoeba appear to be much more common than previously thought, especially so in healthy individuals. While increasing evidence appears to suggest limited pathogenicity of these parasites, next-generation-sequencing-based studies have helped us to appreciate links between parasite colonisation and certain host phenotypical characteristics and gut microbial profiles. The fundamental question remains as to whether such parasites are merely indicators or active manipulators of gut microbiota structure and function. In this article, we collate existing evidence that these parasites are, at minimum, indicators of intestinal microbiota structure.}, } @article {pmid29566771, year = {2018}, author = {Callens, M and Watanabe, H and Kato, Y and Miura, J and Decaestecker, E}, title = {Microbiota inoculum composition affects holobiont assembly and host growth in Daphnia.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {56}, pmid = {29566771}, issn = {2049-2618}, support = {FWO G060216N//FWO/International ; BOF C16/17/002//KU Leuven/International ; }, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacterial Load ; Biodiversity ; Daphnia/drug effects/growth & development/*microbiology/*physiology ; *Host Microbial Interactions/drug effects ; *Microbiota/drug effects ; }, abstract = {BACKGROUND: Host-associated microbiota is often acquired by horizontal transmission of microbes present in the environment. It is hypothesized that differences in the environmental pool of colonizers can influence microbiota community assembly on the host and as such affect holobiont composition and host fitness. To investigate this hypothesis, the host-associated microbiota of the invertebrate eco(toxico)logical model Daphnia was experimentally disturbed using different concentrations of the antibiotic oxytetracycline. The community assembly and host-microbiota interactions when Daphnia were colonized by the disturbed microbiota were investigated by inoculating germ-free individuals with the microbiota.

RESULTS: Antibiotic-induced disturbance of the microbiota had a strong effect on the subsequent colonization of Daphnia by affecting ecological interactions between members of the microbiota. This resulted in differences in community assembly which, in turn, affected Daphnia growth.

CONCLUSIONS: These results show that the composition of the pool of colonizing microbiota can be an important structuring factor of the microbiota assembly on Daphnia, affecting holobiont composition and host growth. These findings contribute to a better understanding of how the microbial environment can shape the holobiont composition and affect host-microbiota interactions.}, } @article {pmid29566748, year = {2018}, author = {Miranda, PM and De Palma, G and Serkis, V and Lu, J and Louis-Auguste, MP and McCarville, JL and Verdu, EF and Collins, SM and Bercik, P}, title = {High salt diet exacerbates colitis in mice by decreasing Lactobacillus levels and butyrate production.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {57}, pmid = {29566748}, issn = {2049-2618}, support = {SFRH / BD / 51278 / 2010//Fundação para a Ciência e a Tecnologia/International ; //CIHR/Canada ; }, mesh = {Animals ; Butyrates/*metabolism ; Colitis/*etiology/*metabolism/pathology ; *Diet ; Disease Models, Animal ; Disease Progression ; Fatty Acids/metabolism ; *Gastrointestinal Microbiome ; Interleukin-17/metabolism ; Intestinal Mucosa/immunology/metabolism/microbiology ; *Lactobacillus ; Male ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 3/metabolism ; RNA, Ribosomal, 16S/genetics ; *Salts ; T-Lymphocytes/immunology/metabolism ; }, abstract = {BACKGROUND: Changes in hygiene and dietary habits, including increased consumption of foods high in fat, simple sugars, and salt that are known to impact the composition and function of the intestinal microbiota, may explain the increase in prevalence of chronic inflammatory diseases. High salt consumption has been shown to worsen autoimmune encephalomyelitis and colitis in mouse models through p38/MAPK signaling pathway. However, the effect of high salt diet (HSD) on gut microbiota and on intestinal immune homeostasis, and their roles in determining vulnerability to intestinal inflammatory stimuli are unknown. Here, we investigate the role of gut microbiota alterations induced by HSD on the severity of murine experimental colitis.

RESULTS: Compared to control diet, HSD altered fecal microbiota composition and function, reducing Lactobacillus sp. relative abundance and butyrate production. Moreover, HSD affected the colonic, and to a lesser extent small intestine mucosal immunity by enhancing the expression of pro-inflammatory genes such as Rac1, Map2k1, Map2k6, Atf2, while suppressing many cytokine and chemokine genes, such as Ccl3, Ccl4, Cxcl2, Cxcr4, Ccr7. Conventionally raised mice fed with HSD developed more severe DSS- (dextran sodium sulfate) and DNBS- (dinitrobenzene sulfonic acid) induced colitis compared to mice on control diet, and this effect was absent in germ-free mice. Transfer experiments into germ-free mice indicated that the HSD-associated microbiota profile is critically dependent on continued exposure to dietary salt.

CONCLUSIONS: Our results indicate that the exacerbation of colitis induced by HSD is associated with reduction in Lactobacillus sp. and protective short-chain fatty acid production, as well as changes in host immune status. We hypothesize that these changes alter gut immune homeostasis and lead to increased vulnerability to inflammatory insults.}, } @article {pmid29566746, year = {2018}, author = {Sloan, RA and Kim, Y and Sahasranaman, A and Müller-Riemenschneider, F and Biddle, SJH and Finkelstein, EA}, title = {The influence of a consumer-wearable activity tracker on sedentary time and prolonged sedentary bouts: secondary analysis of a randomized controlled trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {189}, pmid = {29566746}, issn = {1756-0500}, support = {NCT01855776//Ministry of Health -Singapore/ ; }, mesh = {Accelerometry/*instrumentation ; Adult ; Aged ; Exercise/*physiology ; Female ; *Fitness Trackers ; Health Promotion/methods ; Humans ; Male ; Middle Aged ; Outcome Assessment (Health Care)/methods/statistics & numerical data ; *Sedentary Behavior ; Time Factors ; Young Adult ; }, abstract = {OBJECTIVE: A recent meta-analysis surmised pedometers were a useful panacea to independently reduce sedentary time (ST). To further test and expand on this deduction, we analyzed the ability of a consumer-wearable activity tracker to reduce ST and prolonged sedentary bouts (PSB). We originally conducted a 12-month randomized control trial where 800 employees from 13 organizations were assigned to control, activity tracker, or one of two activity tracker plus incentive groups designed to increase step count. The primary outcome was accelerometer measured moderate-to-vigorous physical activity.

RESULTS: We conducted a secondary analysis on accelerometer measured daily ST and PSB bouts. A general linear mixed model was used to examine changes in ST and prolonged sedentary bouts, followed by between-group pairwise comparisons. Regression analyses were conducted to examine the association of changes in step counts with ST and PSB. The changes in ST and PSB were not statistically significant and not different between the groups (P < 0.05). Increases in step counts were concomitantly associated with decreases in ST and PSB, regardless of intervention (P < 0.05). Caution should be taken when considering consumer-wearable activity trackers as a means to reduce sedentary behavior. Trial registration NCT01855776 Registered: August 8, 2012.}, } @article {pmid29566743, year = {2018}, author = {Iqbal, N and Khan, ZA and Anwar, SMH and Irfan, O and Irfan, B and Mushtaq, A and Bibi, M and Siddiqui, F and Khan, JA}, title = {Electronic cigarettes use and perception amongst medical students: a cross sectional survey from Sindh, Pakistan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {188}, pmid = {29566743}, issn = {1756-0500}, mesh = {Awareness ; Cross-Sectional Studies ; *Electronic Nicotine Delivery Systems ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Logistic Models ; Male ; Multivariate Analysis ; Pakistan ; Perception ; Students, Medical/psychology/*statistics & numerical data ; *Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: The manufacturers of electronic cigarettes (e-cigarettes) are actively marketing their product through electronic and social media. Undergraduate medical students are expected to have better knowledge and awareness as they directly interact with patients in their training, The purpose of this study is therefore, to determine knowledge, use and perception regarding e-cigarettes among medical students from Sindh, Pakistan.

RESULTS: A cross-sectional study was conducted between 1st July and 30th September 2016 at five different medical colleges situated in the second largest province of Sindh, Pakistan. The data was collected through a structured, self-administered questionnaire. Of the 500 students, the mean age was 21.5 ± 1.7 years and 58% were females. Over (65.6%) students were aware of e-cigarettes, 31 (6.2%) reported having used e-cigarettes, of whom 6 (1.2%) self-reported daily use. Users of conventional tobacco products were significantly more likely to have heard of e-cigarettes (87.6% vs 51.6%, p < 0.001) and having used them (13.9% vs 1.3%, p < 0.001). On multivariable logistic regression analysis we found a strong association of e-cigarette use with consumption of conventional cigarettes [OR: 10.6, 95% CI 3.6-30.8, p < 0.001], use of smokeless tobacco products [OR: 7.9, 95% CI 2.7-23.4, p < 0.001] however a weak association was observed for Shisha use [OR: 3.05, 95% CI 0.9-9.6, p = 0.05].}, } @article {pmid29566738, year = {2018}, author = {Singh, R and de Groot, PF and Geerlings, SE and Hodiamont, CJ and Belzer, C and Berge, IJMT and de Vos, WM and Bemelman, FJ and Nieuwdorp, M}, title = {Fecal microbiota transplantation against intestinal colonization by extended spectrum beta-lactamase producing Enterobacteriaceae: a proof of principle study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {190}, pmid = {29566738}, issn = {1756-0500}, support = {016.146.327//zonmw vidi/ ; 024.002.002//nwo gravitation grant/ ; }, mesh = {Adult ; Aged ; Enterobacteriaceae/enzymology/*physiology ; Enterobacteriaceae Infections/microbiology/*therapy ; Fecal Microbiota Transplantation/*methods ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Intestines/*microbiology ; Male ; Middle Aged ; Time Factors ; Treatment Outcome ; Young Adult ; beta-Lactamases/*metabolism ; }, abstract = {OBJECTIVE: Infections with multidrug-resistant microorganisms are associated with increased hospitalization, medication costs and mortality. Based on our fecal microbiota transplantation (FMT) experience for Clostridium difficile infection, we treated 15 patients carrying ESBL-producing Enterobacteriaceae (ESBL-EB) with FMT. Seven patients underwent a second FMT after 4 weeks when ESBL-EB remained, amounting to a total number of 22 transplants. The objective was decolonization of ESBL-EB.

RESULTS: Three out of fifteen (20%) patients were ESBL-negative at 1, 2 and 4 weeks after the first transplant, while six out of 15 (40%) were negative after the second transplant. Comparison of fecal microbiota at baseline and 4 weeks after FMT revealed restoration of microbial diversity after FMT and a microbial shift towards donor composition. Finally, we suggest several possible factors of response to therapy, such as donor-recipient microbiota match and number of FMTs. Therefore, FMT can be an effective treatment in patients carrying ESBL-EB. Response may be determined by microbiota composition and number of FMT procedures. Trial registration ISRCTN ISRCTN48328635 Registered 11 October 2017, retrospectively registered.}, } @article {pmid29566724, year = {2018}, author = {Wanyenze, RK and Goggin, K and Finocchario-Kessler, S and Beyeza-Kashesya, J and Mindry, D and Birungi, J and Woldetsadik, M and Wagner, GJ}, title = {Utilization of prevention of mother-to-child transmission (PMTCT) services among pregnant women in HIV care in Uganda: a 24-month cohort of women from pre-conception to post-delivery.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {187}, pmid = {29566724}, issn = {1756-0500}, support = {R01 HD072633/HD/NICHD NIH HHS/United States ; 5R01HD072633//National Institutes of Health/ ; }, mesh = {Adult ; Anti-HIV Agents/therapeutic use ; Cohort Studies ; Female ; HIV Infections/drug therapy/*prevention & control/transmission ; Humans ; Infant, Newborn ; Infectious Disease Transmission, Vertical/*prevention & control ; Interviews as Topic ; Pregnancy ; Pregnancy Complications, Infectious/*prevention & control ; Pregnancy Outcome ; Prenatal Care/*statistics & numerical data ; Uganda ; }, abstract = {OBJECTIVE: We assessed the uptake of prevention of mother-to-child transmission (PMTCT) services in a cohort of HIV infected women in care at The AIDS Support Organization Jinja and Kampala in Uganda, who were trying to conceive, over a period of 24 months, to inform the strengthening of PMTCT service access for women in care.

RESULTS: Of the 299 women 127 (42.5%) reported at least one pregnancy within 24 months; 61 women (48.0%) delivered a live child. Of the 55 who had a live birth at the first pregnancy, 54 (98.2%) used antenatal care (ANC) starting at 15.5 weeks of gestation on average and 47/49 (95.9%) delivered at a health facility. Excluding miscarriages, 54 (98.2%) received ARVs during pregnancy. Of the 49 live births with post-delivery data, 37 (75.5%) tested the infant for HIV. 79 of the 127 (68.7%) spoke with providers about childbearing. Communication with providers was associated with ANC use (65.8% vs. 41.7%; p = .015). Despite the high rate of miscarriages and late ANC start, this study shows very high uptake of PMTCT services among PLHIV in care and their infants. Improved provider-client communication could enhance ANC attendance and PMTCT outcomes among HIV infected women in care.}, } @article {pmid29566674, year = {2018}, author = {Ancot, F and Lemay, P and Knowler, SP and Kennedy, K and Griffiths, S and Cherubini, GB and Sykes, J and Mandigers, PJJ and Rouleau, GA and Rusbridge, C and Kibar, Z}, title = {A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {16}, pmid = {29566674}, issn = {1471-2156}, abstract = {BACKGROUND: Syringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance.

RESULTS: We identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development.

CONCLUSIONS: We identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.}, } @article {pmid29566671, year = {2018}, author = {Huang, L and Liao, L and Wu, CH}, title = {Completing sparse and disconnected protein-protein network by deep learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {103}, pmid = {29566671}, issn = {1471-2105}, support = {P20 GM103446/GM/NIGMS NIH HHS/United States ; P20 GM103446-12/NH/NIH HHS/United States ; }, mesh = {*Algorithms ; Area Under Curve ; Bayes Theorem ; Humans ; *Machine Learning ; Neural Networks (Computer) ; *Protein Interaction Maps ; Proteins/metabolism ; ROC Curve ; Saccharomyces cerevisiae/metabolism ; }, abstract = {BACKGROUND: Protein-protein interaction (PPI) prediction remains a central task in systems biology to achieve a better and holistic understanding of cellular and intracellular processes. Recently, an increasing number of computational methods have shifted from pair-wise prediction to network level prediction. Many of the existing network level methods predict PPIs under the assumption that the training network should be connected. However, this assumption greatly affects the prediction power and limits the application area because the current golden standard PPI networks are usually very sparse and disconnected. Therefore, how to effectively predict PPIs based on a training network that is sparse and disconnected remains a challenge.

RESULTS: In this work, we developed a novel PPI prediction method based on deep learning neural network and regularized Laplacian kernel. We use a neural network with an autoencoder-like architecture to implicitly simulate the evolutionary processes of a PPI network. Neurons of the output layer correspond to proteins and are labeled with values (1 for interaction and 0 for otherwise) from the adjacency matrix of a sparse disconnected training PPI network. Unlike autoencoder, neurons at the input layer are given all zero input, reflecting an assumption of no a priori knowledge about PPIs, and hidden layers of smaller sizes mimic ancient interactome at different times during evolution. After the training step, an evolved PPI network whose rows are outputs of the neural network can be obtained. We then predict PPIs by applying the regularized Laplacian kernel to the transition matrix that is built upon the evolved PPI network. The results from cross-validation experiments show that the PPI prediction accuracies for yeast data and human data measured as AUC are increased by up to 8.4 and 14.9% respectively, as compared to the baseline. Moreover, the evolved PPI network can also help us leverage complementary information from the disconnected training network and multiple heterogeneous data sources. Tested by the yeast data with six heterogeneous feature kernels, the results show our method can further improve the prediction performance by up to 2%, which is very close to an upper bound that is obtained by an Approximate Bayesian Computation based sampling method.

CONCLUSIONS: The proposed evolution deep neural network, coupled with regularized Laplacian kernel, is an effective tool in completing sparse and disconnected PPI networks and in facilitating integration of heterogeneous data sources.}, } @article {pmid29566669, year = {2018}, author = {Adrian-Kalchhauser, I and Walser, JC and Schwaiger, M and Burkhardt-Holm, P}, title = {RNA sequencing of early round goby embryos reveals that maternal experiences can shape the maternal RNA contribution in a wild vertebrate.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {34}, pmid = {29566669}, issn = {1471-2148}, mesh = {Animals ; Animals, Wild/*genetics ; Base Sequence ; Embryo, Nonmammalian/*metabolism ; Embryonic Development/genetics ; Female ; Gene Expression Regulation, Developmental ; Perciformes/*embryology/*genetics ; Principal Component Analysis ; RNA/*metabolism ; Sequence Analysis, RNA/*methods ; Signal Transduction/genetics ; Temperature ; }, abstract = {BACKGROUND: It has been proposed that non-genetic inheritance could promote species fitness. Non-genetic inheritance could allow offspring to benefit from the experience of their parents, and could advocate pre-adaptation to prevailing and potentially selective conditions. Indeed, adaptive parental effects have been modeled and observed, but the molecular mechanisms behind them are far from understood.

RESULTS: In the present study, we investigated whether maternal RNA can carry information about environmental conditions experienced by the mother in a wild vertebrate. Maternal RNA directs the development of the early embryo in many non-mammalian vertebrates and invertebrates. However, it is not known whether vertebrate maternal RNA integrates information about the parental environment. We sequenced the maternal RNA contribution from a model that we expected to rely on parental effects: the invasive benthic fish species Neogobius melanostomus (Round Goby). We found that maternal RNA expression levels correlated with the water temperature experienced by the mother before oviposition, and identified temperature-responsive gene groups such as core nucleosome components or the microtubule cytoskeleton.

CONCLUSIONS: Our findings suggest that the maternal RNA contribution may incorporate environmental information. Maternal RNA should therefore be considered a potentially relevant pathway for non-genetic inheritance. Also, the ability of a species to integrate environmental information in the maternal RNA contribution could potentially contribute to species fitness and may also play a role in extraordinary adaptive success stories of invasive species such as the round goby.}, } @article {pmid29566664, year = {2018}, author = {Liberti, J and Baer, B and Boomsma, JJ}, title = {Rival seminal fluid induces enhanced sperm motility in a polyandrous ant.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {28}, pmid = {29566664}, issn = {1471-2148}, support = {323085//European Research Council/International ; 323085//H2020 European Research Council/International ; }, mesh = {Animals ; Ants/*physiology ; Female ; Male ; Reproduction ; Semen/*metabolism ; Sexual Behavior, Animal ; Sperm Motility/*physiology ; Spermatozoa/physiology ; }, abstract = {BACKGROUND: Promiscuous mating and sperm competition often induce arms races between the sexes with detrimental outcomes for females. However, ants with multiply-inseminated queens have only a single time-window for sperm competition and queens are predicted to gain control over the outcome of sperm storage quickly. The seminal fluid of Acromyrmex leaf-cutting ants reduces the viability of rival sperm, but how confrontations between unrelated ejaculates affect sperm storage remains unknown.

RESULTS: We investigated the effects of ejaculate admixture on sperm motility in A. echinatior and found that the proportion of motile spermatozoa, sperm swimming speed, and linearity of sperm movement increased when rival ejaculates were mixed in vitro. Major effects induced by the seminal fluid of rival males were of similar magnitude to those generated by queen reproductive tract secretions, whereas own seminal fluid induced lower sperm activation levels.

CONCLUSIONS: Our results suggest that ant sperm respond via a self-non-self recognition mechanism to similar or shared molecules expressed in the reproductive secretions of both sexes. Lower sperm motility in the presence of own seminal fluid indicates that enhanced motility is costly and may trade-off with sperm viability during sperm storage, consistent with studies in vertebrates. Our results imply that ant spermatozoa have evolved to adjust their energetic expenditure during insemination depending on the perceived level of sperm competition.}, } @article {pmid29566663, year = {2018}, author = {Chen, F and Zhang, W and Yu, K and Sun, L and Gao, J and Zhou, X and Peng, Q and Fu, S and Hu, M and Long, W and Pu, H and Chen, S and Wang, X and Zhang, J}, title = {Unconditional and conditional QTL analyses of seed fatty acid composition in Brassica napus L.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {49}, pmid = {29566663}, issn = {1471-2229}, support = {31601334//National Natural Science Foundation of China/ ; 31371660//National Natural Science Foundation of China/ ; CARS-12//the Earmarked Fund for China Agriculture Research System/ ; 2014BAD01B07//National Science and Technology Support Program/ ; BK20160578//Natural Science Foundation of Jiangsu Province/ ; }, mesh = {Brassica napus/genetics/*metabolism ; Fatty Acids/metabolism ; Germination/genetics/physiology ; Quantitative Trait Loci/*genetics ; Seeds/genetics/*metabolism ; }, abstract = {BACKGROUND: The fatty acid composition of B. napus' seeds determines the oil's nutritional and industrial values, and affects seed germination. Many studies have reported correlations among C16:0, C18:0, C18:1, C18:2 and C18:3 based on phenotypic data; however, the genetic basis of the fatty acid composition in B. napus is still not well understood.

RESULTS: In this study, unconditional and conditional quantitative trail locus (QTL) mapping analyses were conducted using a recombinant inbred line in six environments. In total, 21 consensus QTLs each for C16:0, C18:0 and C18:2, 16 for C18:1 and 22 for C18:3 were detected by unconditional mapping. The QTLs with overlapping confidence intervals were integrated into 71 pleiotropically unique QTLs by meta-analysis. Two major QTLs, uuqA5-6 and uuqA5-7, simultaneously affected the fatty acids, except C18:0, in most of environments, with the homologous genes fatty acid desaturase 2 (FAD2) and glycerol-3-phosphate sn-2-acyltransferase 5 (GPAT5) occurring in the confidence interval of uuqA5-6, while phosphatidic acid phosphohydrolase 1 (PAH1) was assigned to uuqA5-7. Moreover, 49, 30, 48, 60 and 45 consensus QTLs were detected for C16:0, C18:0, C18:1, C18:2 and C18:3, respectively, by the conditional mapping analysis. In total, 128 unique QTLs were subsequently integrated from the 232 conditional consensus QTLs. A comparative analysis revealed that 63 unique QTLs could be identified by both mapping methodologies, and 65 additional unique QTLs were only identified in conditional mapping.

CONCLUSIONS: Thus, conditional QTL mapping for fatty acids may uncover numerous additional QTLs that were inhibited by the effects of other traits. These findings provide useful information for better understanding the genetic relationships among fatty acids at the QTL level.}, } @article {pmid29566661, year = {2018}, author = {Khosravi, C and Battaglia, E and Kun, RS and Dalhuijsen, S and Visser, J and Aguilar-Pontes, MV and Zhou, M and Heyman, HM and Kim, YM and Baker, SE and de Vries, RP}, title = {Blocking hexose entry into glycolysis activates alternative metabolic conversion of these sugars and upregulates pentose metabolism in Aspergillus nidulans.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {214}, pmid = {29566661}, issn = {1471-2164}, support = {016.130.609//Stichting voor de Technische Wetenschappen/International ; DE- SC0008744//Office of Science/International ; }, mesh = {Aspergillus nidulans/growth & development/*metabolism ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Glucokinase/genetics/metabolism ; *Glycolysis ; Hexokinase/genetics/metabolism ; Hexoses/*metabolism ; Metabolomics ; Pentoses/*metabolism ; }, abstract = {BACKGROUND: Plant biomass is the most abundant carbon source for many fungal species. In the biobased industry fungi, are used to produce lignocellulolytic enzymes to degrade agricultural waste biomass. Here we evaluated if it would be possible to create an Aspergillus nidulans strain that releases, but does not metabolize hexoses from plant biomass. For this purpose, metabolic mutants were generated that were impaired in glycolysis, by using hexokinase (hxkA) and glucokinase (glkA) negative strains. To prevent repression of enzyme production due to the hexose accumulation, strains were generated that combined these mutations with a deletion in creA, the repressor involved in regulating preferential use of different carbon catabolic pathways.

RESULTS: Phenotypic analysis revealed reduced growth for the hxkA1 glkA4 mutant on wheat bran. However, hexoses did not accumulate during growth of the mutants on wheat bran, suggesting that glucose metabolism is re-routed towards alternative carbon catabolic pathways. The creAΔ4 mutation in combination with preventing initial phosphorylation in glycolysis resulted in better growth than the hxkA/glkA mutant and an increased expression of pentose catabolic and pentose phosphate pathway genes. This indicates that the reduced ability to use hexoses as carbon sources created a shift towards the pentose fraction of wheat bran as a major carbon source to support growth.

CONCLUSION: Blocking the direct entry of hexoses to glycolysis activates alternative metabolic conversion of these sugars in A. nidulans during growth on plant biomass, but also upregulates conversion of other sugars, such as pentoses.}, } @article {pmid29566660, year = {2018}, author = {Isakova, J and Sovkhozova, N and Vinnikov, D and Goncharova, Z and Talaibekova, E and Aldasheva, N and Aldashev, A}, title = {Mutations of rpoB, katG, inhA and ahp genes in rifampicin and isoniazid-resistant Mycobacterium tuberculosis in Kyrgyz Republic.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {22}, pmid = {29566660}, issn = {1471-2180}, abstract = {BACKGROUND: The aim of this study was to identify mutations of rpoB, katG, inhA and ahp-genes associated Mycobacterium tuberculosis resistance to rifampicin (RIF) and isoniazid (INH) in Kyrgyz Republic. We studied 633 smear samples from the primary pulmonary tuberculosis (TB) patients. We verified Mycobacterium tuberculosis susceptibility to RIF and INH using culture method of absolute concentrations, and commercially available test named "TB-BIOCHIP" (Biochip-IMB, Moscow, Russian Federation).

RESULTS: For RIF-resistance, TB-BIOCHIP's sensitivity and specificity were 88% and 97%, 84% and 95% for INH-resistance, and 90% and 97% for multi-drug resistance (MDR). In RIF-resistant strains, TB-BIOCHIP showed mutations in codons 531 (64.8%), 526 (17.3%), 516 (8.1%), 511 (5.4%), 533 (3.2%), 522 (0.6%) and 513 (0.6%) of rpoB gene. The most prevalent was Ser531 > Leu mutation (63.7%). 91.2% of mutations entailing resistance to INH were in katG gene, 7% in inhA gene, and 1.8% in ahpC gene. Ser315→Thr (88.6%) was the most prevalent mutation leading to resistance to INH.

CONCLUSIONS: In Kyrgyz Republic, the most prevalent mutation in RIF-resistant strains was Ser531 → Leu in rpoB gene, as opposed to Ser315 → Thr in katG gene in INH-resistant Mycobacterium tuberculosis. In Kyrgyz Republic, the major reservoir of MDR Mycobacterium tuberculosis were strains with combined mutations Ser531 → Leu in rpoB gene and Ser315 → Thr in katG gene. TB-BIOCHIP has shown moderate sensitivity with the advantage of obtaining results in only two days.}, } @article {pmid29566653, year = {2018}, author = {Tian, M and Nie, Q and Li, Z and Zhang, J and Liu, Y and Long, Y and Wang, Z and Wang, G and Liu, R}, title = {Transcriptomic analysis reveals overdominance playing a critical role in nicotine heterosis in Nicotiana tabacum L.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {48}, pmid = {29566653}, issn = {1471-2229}, support = {[2015]4011 and 20165663//The Talent and Team Cultivation Project for High-Level Renovation Plan of Guizhou Province/ ; 201302 and 201602//Key projects from the Guizhou Provincial Tobacco Company of China National Tobacco Corporation/ ; }, mesh = {Gene Expression Profiling/*methods ; Gene Expression Regulation, Plant/genetics/physiology ; Hybrid Vigor/genetics/physiology ; Nicotine/*metabolism ; Tobacco/*genetics/*physiology ; }, abstract = {BACKGROUND: As a unique biological phenomenon, heterosis has been concerned with the superior performance of the heterosis than either parents. Despite several F1 hybrids, containing supernal nicotine content, had been discovered and applied to heterosis utilization in Nicotiana tabacum L., nevertheless, the potential molecular mechanism revealing nicotine heterosis has not been illustrated clearly.

RESULT: Phenotypically, the F1 hybrids (Vall6 × Basma) show prominent heterosis in nicotine content by 3 years of field experiments. Transcriptome analysis revealed that genes participating in nicotine anabolism (ADC, PMT, MPO, QPT, AO, QS, QPT, A622, BBLs) and nicotine transport (JAT2, MATE1 and 2, NUP1 and 2) showed an upregulated expression in the hybrid, a majority of which demonstrated an overdominant performance. RT-PCR confirmed that nicotine anabolism was induced in the hybrid.

CONCLUSIONS: These findings strongly suggest that nicotine synthesis and transport efficiency improved in hybrid and overdominance at gene-expression level played a critical role in heterosis of nicotine metabolism.}, } @article {pmid29566568, year = {2018}, author = {Ponseti, J and Dähnke, K and Fischermeier, L and Gerwinn, H and Kluth, A and Müller, J and Vogel, S and Stirn, A}, title = {Sexual Responses Are Facilitated by High-Order Contextual Cues in Females but Not in Males.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704918761103}, doi = {10.1177/1474704918761103}, pmid = {29566568}, issn = {1474-7049}, mesh = {Adult ; *Cues ; Female ; Humans ; Male ; Pattern Recognition, Visual/*physiology ; *Sex Characteristics ; Sexual Behavior/*physiology ; *Social Perception ; Young Adult ; }, abstract = {Sexual responses are thought to be controlled by a brain module called the sexual module. Sexual strategies of males and females vary to a great extent, and sexual responses of males and females may be affected by their sexual strategies. However, the current view of the sexual module is that of a unisex module. This might be questionable since brain modules are defined as evolved cognitive mechanisms to solve adaptive problems which are different for males and females. We hypothesize that the sexual module responds differently in the presence of complex (high-order) contextual cues that are related to gender-dimorphic sexual strategies in males and females. We conducted a priming experiment in which stimuli related to sexual strategies were disentangled from their sexual meaning. Nonsexual priming pictures related to either economic resources or social interactions preceded a sexual-target picture in order to test whether the primes were able to modulate the subjective sexual response to the sexual target. In a control condition, priming pictures without relation to mating preferences but with similar emotional impact were presented. In males, sexual responses were similar in the experimental and control conditions. In females, however, primes related to economic resources or social interactions modulated sexual arousal significantly more than the control primes. Our findings suggest that brain modules dedicated to process the experimental primes were functionally connected with the sexual module in females more than in males, making females' sexual responses more prone to the impact of high-order cultural cues than males' sexual responses. A gender-dimorphic connectivity of the sexual module may be the way in which gender-dimorphic sexual strategies are implemented in the human mind.}, } @article {pmid29566459, year = {2018}, author = {Robertson, HM and Baits, RL and Walden, KKO and Wada-Katsumata, A and Schal, C}, title = {Enormous expansion of the chemosensory gene repertoire in the omnivorous German cockroach Blattella germanica.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {5}, pages = {265-278}, pmid = {29566459}, issn = {1552-5015}, abstract = {The acquisition of genome sequences from a wide range of insects and other arthropods has revealed a broad positive correlation between the complexity of their chemical ecology and the size of their chemosensory gene repertoire. The German cockroach Blattella germanica is an extreme omnivore and has the largest chemosensory gene repertoire known for an arthropod, exceeding even the highly polyphagous spider mite Tetranychus urticae. While the Odorant Receptor family is not particularly large, with 123 genes potentially encoding 134 receptors (105 intact), the Gustatory Receptor family is greatly expanded to 431 genes potentially encoding 545 receptors (483 intact), the largest known for insects and second only to the spider mite. The Ionotropic Receptor family of olfactory and gustatory receptors is vastly expanded to at least 897 genes (604 intact), the largest size known in arthropods, far surpassing the 150 known from the dampwood termite Zootermopsis nevadensis. Commensurately, the Odorant Binding Protein family is expanded to the largest known for insects at 109 genes (all intact). Comparison with the far more specialized, but phylogenetically related termite, within the Dictyoptera, reveals considerable gene losses from the termite, and massive species-specific gene expansions in the cockroach. The cockroach has lost function of 11%-41% of these three chemoreceptor gene families to pseudogenization, and most of these are young events, implying rapid turnover of genes along with these major expansions, presumably in response to changes in its chemical ecology.}, } @article {pmid29566225, year = {2018}, author = {Larson, CA and Mirza, B and Rodrigues, JLM and Passy, SI}, title = {Iron limitation effects on nitrogen-fixing organisms with possible implications for cyanobacterial blooms.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy046}, pmid = {29566225}, issn = {1574-6941}, abstract = {Cyanobacteria-dominated harmful algal blooms are increasing in occurrence. Many of the taxa contributing to these blooms are capable of fixing atmospheric nitrogen and should be favored under conditions of low nitrogen availability. Yet, synthesizing nitrogenase, the enzyme responsible for nitrogen fixation, is energetically expensive and requires substantial concentrations of iron. Phosphorus addition to nitrogen poor streams should promote nitrogen fixation, but experimental results so far have been inconclusive, suggesting that other factors may be involved in controlling this process. With iron potentially limited in many streams, we examined the influence of phosphorus-iron colimitation on the community structure of nitrogen-fixing organisms. In stream microcosms, using microscopic and molecular sequence data, we observed: (i) the greatest abundance of heterocyst forming nitrogen-fixing cyanobacteria in low nitrogen treatments with high phosphorus and iron and (ii) greater abundance of non-photosynthetic nitrogen-fixing bacteria in treatments with nitrogen compared to those without it. We also found that comparisons between molecular results and those obtained from microscopic identification provided complementary information about cyanobacterial communities. Our investigation indicates the potential for phosphorus-iron colimitation of stream nitrogen-fixing organisms.}, } @article {pmid29566154, year = {2018}, author = {Gargari, G and Deon, V and Taverniti, V and Gardana, C and Denina, M and Riso, P and Guardamagna, O and Guglielmetti, S}, title = {Evidence of dysbiosis in the intestinal microbial ecosystem of children and adolescents with primary hyperlipidemia and the potential role of regular hazelnut intake.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy045}, pmid = {29566154}, issn = {1574-6941}, abstract = {Hyperlipidemia starts at a pediatric age and represents an unquestionable risk factor for cardiovascular disease. Modulation of the intestinal microbial ecosystem (IME), in principle, can ameliorate lipid profiles. In this study, we characterized the IME of children and adolescents with primary hyperlipidemia by analyzing fecal samples through 16S rRNA gene profiling (n = 15) and short chain fatty acid (SCFA) quantification (n = 32). The same analyses were also carried out on age-matched normolipidemic controls (n = 15). Moreover, we evaluated the modulatory effect of regular hazelnut intake (approximately 0.43 g of hazelnuts with skin per kg of body weight) on the IME of 15 children and adolescents with hyperlipidemia for eight weeks. We found alterations of numerous operational taxonomic units potentially associated with SCFA-producing bacteria and reductions in the fecal levels of acetate, butyrate and propionate in hyperlipidemic subjects. Furthermore, we observed that an eight-week hazelnut intervention may induce limited changes in fecal microbiota composition but can significantly modulate the fecal levels of predominant intestinal SCFAs, such as acetate. Finally, correlation analyses indicated that changes in lipidemic parameters are linked to modifications of the abundance of specific bacterial taxa, such as the families Lachnospiraceae and Ruminococcaceae and the genera Akkermansia, Bacteroides, Roseburia, and Faecalibacterium. This study suggests that children and adolescents with primary hyperlipidemia possess an altered IME. The promising results presented here support the need for future dietary interventions aimed at positively modulating the IME of hyperlipidemic subjects.}, } @article {pmid29565415, year = {2018}, author = {Jasanoff, S and Hurlbut, JB}, title = {A global observatory for gene editing.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {435-437}, doi = {10.1038/d41586-018-03270-w}, pmid = {29565415}, issn = {1476-4687}, mesh = {Animals ; Congresses as Topic ; Gene Editing/*ethics ; Humans ; *International Cooperation ; Morals ; Public Opinion ; *Risk Assessment ; Social Change ; }, } @article {pmid29565413, year = {2018}, author = {Cyranoski, D}, title = {Chinese leaders create science mega-ministry.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {425-426}, doi = {10.1038/d41586-018-03246-w}, pmid = {29565413}, issn = {1476-4687}, mesh = {China ; Endangered Species ; Environmental Policy ; *Federal Government ; *Leadership ; Science/economics/*legislation & jurisprudence/*organization & administration ; Workforce ; }, } @article {pmid29565412, year = {2018}, author = {Osumi, N}, title = {Calling rikejo.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S59}, doi = {10.1038/d41586-018-02906-1}, pmid = {29565412}, issn = {1476-4687}, mesh = {Authorship ; Child ; Child Care/supply & distribution ; Faculty/statistics & numerical data ; Humans ; Japan ; Research Personnel/education/*statistics & numerical data ; Sex Distribution ; Sexism/*statistics & numerical data ; Universities ; Work-Life Balance ; Workforce ; }, } @article {pmid29565411, year = {2018}, author = {}, title = {A guide to the Nature Index.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S74}, doi = {10.1038/d41586-018-02904-3}, pmid = {29565411}, issn = {1476-4687}, mesh = {Academies and Institutes/standards/statistics & numerical data ; *Authorship ; *Bibliometrics ; Internationality ; Periodicals as Topic ; Research/standards/*statistics & numerical data ; Workforce ; }, } @article {pmid29565410, year = {2018}, author = {Tollefson, J}, title = {Advances in human behaviour came surprisingly early in Stone Age.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {424-425}, doi = {10.1038/d41586-018-03244-y}, pmid = {29565410}, issn = {1476-4687}, } @article {pmid29565409, year = {2018}, author = {Extance, A}, title = {How atomic imaging is being pushed to its limit.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {545-547}, doi = {10.1038/d41586-018-03305-2}, pmid = {29565409}, issn = {1476-4687}, mesh = {Automation ; Machine Learning/trends ; Microscopy, Atomic Force/instrumentation/*methods/*trends ; Oxyquinoline/analysis/chemistry ; }, } @article {pmid29565408, year = {2018}, author = {}, title = {Fourier's transformational thinking.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {413}, doi = {10.1038/d41586-018-03389-w}, pmid = {29565408}, issn = {1476-4687}, } @article {pmid29565407, year = {2018}, author = {Marchant, J}, title = {When antibiotics turn toxic.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {431-433}, doi = {10.1038/d41586-018-03267-5}, pmid = {29565407}, issn = {1476-4687}, mesh = {Aminoglycosides/adverse effects ; Animals ; Anti-Bacterial Agents/*adverse effects ; Antioxidants/pharmacology/therapeutic use ; Ciprofloxacin/pharmacology/therapeutic use ; Female ; Fluoroquinolones/*adverse effects/metabolism ; Genetic Testing ; Humans ; Inactivation, Metabolic/genetics ; Levofloxacin/adverse effects ; Male ; Mice ; Mitochondria/drug effects/pathology ; Naphthyridines/adverse effects ; Ofloxacin/adverse effects ; Oxidative Stress/drug effects ; Syndrome ; Topoisomerase II Inhibitors/adverse effects ; United States ; United States Food and Drug Administration ; }, } @article {pmid29565405, year = {2018}, author = {Mallapaty, S}, title = {Pillars of a smart society.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S62-S63}, doi = {10.1038/d41586-018-02899-x}, pmid = {29565405}, issn = {1476-4687}, mesh = {Animals ; Automation/methods ; Automobile Driving ; Biometric Identification/methods/trends ; Humans ; Inventions/*trends ; Japan ; Manikins ; Monitoring, Physiologic/methods/trends ; Robotics/trends ; Smartphone ; *Social Change ; }, } @article {pmid29565404, year = {2018}, author = {Hornyak, T}, title = {Noble halls of discovery.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S73}, doi = {10.1038/d41586-018-02903-4}, pmid = {29565404}, issn = {1476-4687}, mesh = {Japan ; Research/*standards ; Research Personnel/*standards ; Universities/*standards ; Workforce ; }, } @article {pmid29565403, year = {2018}, author = {Nurcahyo, A and Meijaard, E}, title = {Create and empower lead authors from the global south.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {443}, doi = {10.1038/d41586-018-03392-1}, pmid = {29565403}, issn = {1476-4687}, } @article {pmid29565402, year = {2018}, author = {Burall, S}, title = {Rethink public engagement for gene editing.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {438-439}, doi = {10.1038/d41586-018-03269-3}, pmid = {29565402}, issn = {1476-4687}, mesh = {Administrative Personnel ; Animals ; *Communication ; Gene Editing/*ethics ; Humans ; *Public Opinion ; Research Personnel ; Stakeholder Participation ; }, } @article {pmid29565401, year = {2018}, author = {}, title = {Workplace culture can push women out of research.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {551}, doi = {10.1038/d41586-018-03308-z}, pmid = {29565401}, issn = {1476-4687}, } @article {pmid29565400, year = {2018}, author = {Fuyuno, I}, title = {Partners in discovery.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S60}, doi = {10.1038/d41586-018-02897-z}, pmid = {29565400}, issn = {1476-4687}, mesh = {Artificial Intelligence/economics ; Drug Discovery/economics/*organization & administration/*trends ; Drug Industry/economics/organization & administration ; Humans ; Japan ; Public-Private Sector Partnerships/economics/*organization & administration ; Universities/economics/*organization & administration ; }, } @article {pmid29565399, year = {2018}, author = {Maxmen, A}, title = {Deadly Lassa-fever outbreak tests Nigeria's revamped health agency.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {421-422}, doi = {10.1038/d41586-018-03171-y}, pmid = {29565399}, issn = {1476-4687}, mesh = {Government Agencies/*organization & administration/*trends ; Hemorrhagic Fever, Ebola/epidemiology/mortality ; Humans ; Lassa Fever/diagnosis/*epidemiology/*mortality/transmission ; Male ; Nigeria/epidemiology ; Public Health/*trends ; }, } @article {pmid29565398, year = {2018}, author = {Telley, L and Jabaudon, D}, title = {A mixed model of neuronal diversity.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {452-454}, doi = {10.1038/d41586-018-02539-4}, pmid = {29565398}, issn = {1476-4687}, mesh = {*Neurons ; }, } @article {pmid29565397, year = {2018}, author = {Morbidelli, A}, title = {Calcium signals in planetary embryos.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {451-452}, doi = {10.1038/d41586-018-03144-1}, pmid = {29565397}, issn = {1476-4687}, } @article {pmid29565396, year = {2018}, author = {Wimbush, S}, title = {Cryptocurrency mining is neither wasteful nor uneconomic.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {443}, doi = {10.1038/d41586-018-03391-2}, pmid = {29565396}, issn = {1476-4687}, } @article {pmid29565395, year = {2018}, author = {Fuyuno, I}, title = {Resistance to reform.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S52-S53}, doi = {10.1038/d41586-018-02896-0}, pmid = {29565395}, issn = {1476-4687}, mesh = {Authorship ; Efficiency, Organizational ; Investments ; Japan ; Language ; Research/economics/*organization & administration/*standards/statistics & numerical data ; Research Support as Topic ; Students ; Universities/economics/*organization & administration/*standards ; Workforce ; }, } @article {pmid29565394, year = {2018}, author = {Wong, D and Yip, S}, title = {Machine learning classifies cancer.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {446-447}, doi = {10.1038/d41586-018-02881-7}, pmid = {29565394}, issn = {1476-4687}, mesh = {*Algorithms ; Humans ; *Machine Learning ; Neoplasms ; }, } @article {pmid29565393, year = {2018}, author = {}, title = {Spy-poison probe, white rhino and Stephen Hawking - the week in science.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {418-419}, doi = {10.1038/d41586-018-03266-6}, pmid = {29565393}, issn = {1476-4687}, } @article {pmid29565392, year = {2018}, author = {Hornyak, T}, title = {Strength from weakness.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S61}, doi = {10.1038/d41586-018-02898-y}, pmid = {29565392}, issn = {1476-4687}, mesh = {Artificial Intelligence ; Astronomy ; Interdisciplinary Research ; Investments ; Japan ; Science/economics/*standards/*trends ; }, } @article {pmid29565391, year = {2018}, author = {Chung, JB}, title = {Let democracy rule nuclear energy.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {415}, doi = {10.1038/d41586-018-03264-8}, pmid = {29565391}, issn = {1476-4687}, mesh = {Environmental Policy/legislation & jurisprudence ; Humans ; Nuclear Energy/economics/*legislation & jurisprudence/statistics & numerical data ; Republic of Korea ; Safety/legislation & jurisprudence ; }, } @article {pmid29565390, year = {2018}, author = {Pontano Vaites, L and Harper, JW}, title = {Protein aggregates caught stalling.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {449-451}, doi = {10.1038/d41586-018-03000-2}, pmid = {29565390}, issn = {1476-4687}, mesh = {*Protein Aggregates ; Protein Biosynthesis ; *Ribosomes ; }, } @article {pmid29565389, year = {2018}, author = {}, title = {How to get public engagement right.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {413-414}, doi = {10.1038/d41586-018-03388-x}, pmid = {29565389}, issn = {1476-4687}, mesh = {*Community Participation ; Humans ; *Public Opinion ; }, } @article {pmid29565388, year = {2018}, author = {}, title = {Clarification.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {551}, doi = {10.1038/d41586-018-03304-3}, pmid = {29565388}, issn = {1476-4687}, } @article {pmid29565387, year = {2018}, author = {}, title = {Relative gain.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S54-S55}, doi = {10.1038/d41586-018-02905-2}, pmid = {29565387}, issn = {1476-4687}, } @article {pmid29565386, year = {2018}, author = {Singh Chawla, D}, title = {The undercover academic keeping tabs on 'predatory' publishing.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {422-423}, doi = {10.1038/d41586-018-02921-2}, pmid = {29565386}, issn = {1476-4687}, mesh = {Fraud/economics/*statistics & numerical data ; Internet ; Peer Review, Research/standards ; Periodicals as Topic/*standards/*statistics & numerical data ; Publishing/economics/*standards/*statistics & numerical data ; Reproducibility of Results ; }, } @article {pmid29565385, year = {2018}, author = {}, title = {Asymmetry symposium unites economists, physicists and artists.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {414}, doi = {10.1038/d41586-018-03254-w}, pmid = {29565385}, issn = {1476-4687}, } @article {pmid29565384, year = {2018}, author = {Foucart, S and Horel, S}, title = {Risks associated with glyphosate weedkiller resurface.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {443}, doi = {10.1038/d41586-018-03394-z}, pmid = {29565384}, issn = {1476-4687}, mesh = {*Glycine/analogs & derivatives ; *Herbicides ; Risk ; }, } @article {pmid29565383, year = {2018}, author = {Hornyak, T}, title = {Facing down disaster.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S66}, doi = {10.1038/d41586-018-02900-7}, pmid = {29565383}, issn = {1476-4687}, mesh = {Cyclonic Storms ; Disaster Planning/economics/methods/trends ; Disasters/economics/*prevention & control/statistics & numerical data ; Earthquakes ; Forecasting ; Humans ; Japan ; Research/economics/*trends ; }, } @article {pmid29565382, year = {2018}, author = {}, title = {Corrections.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {547}, doi = {10.1038/d41586-018-03303-4}, pmid = {29565382}, issn = {1476-4687}, } @article {pmid29565381, year = {2018}, author = {Mallapaty, S}, title = {Short-term generation.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S67}, doi = {10.1038/d41586-018-02901-6}, pmid = {29565381}, issn = {1476-4687}, mesh = {Employment/economics/*statistics & numerical data ; Entrepreneurship/economics/trends ; *Industry/economics ; Japan ; Research Personnel/economics/*supply & distribution ; Universities/economics ; Workforce ; }, } @article {pmid29565380, year = {2018}, author = {Powell, K}, title = {How to sail smoothly from academia to industry.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {549-551}, doi = {10.1038/d41586-018-03306-1}, pmid = {29565380}, issn = {1476-4687}, mesh = {*Biotechnology ; *Cooperative Behavior ; *Drug Industry ; Group Processes ; *Job Application ; Personnel Selection ; *Research Personnel/education/psychology ; Workforce ; }, } @article {pmid29565378, year = {2018}, author = {}, title = {Correction.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {455}, doi = {10.1038/d41586-018-03301-6}, pmid = {29565378}, issn = {1476-4687}, } @article {pmid29565377, year = {2018}, author = {Cyranoski, D}, title = {How human embryonic stem cells sparked a revolution.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {428-430}, doi = {10.1038/d41586-018-03268-4}, pmid = {29565377}, issn = {1476-4687}, mesh = {Adult Stem Cells/cytology/metabolism ; Animals ; Cell Differentiation/genetics ; Cellular Reprogramming ; Clinical Trials as Topic ; Diabetes Mellitus/pathology/therapy ; Gene Editing ; Glucose/metabolism ; Haplorhini ; *Human Embryonic Stem Cells/cytology/immunology/metabolism/transplantation ; Humans ; Induced Pluripotent Stem Cells/cytology/immunology/metabolism/transplantation ; Macular Degeneration/pathology/therapy ; Mice ; Nuclear Transfer Techniques ; Organoids/cytology/metabolism ; Parkinson Disease/pathology/therapy ; Regenerative Medicine/trends ; *Stem Cell Research ; }, } @article {pmid29565376, year = {2018}, author = {Armitage, C}, title = {Stalled ambition.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S49}, doi = {10.1038/d41586-018-02895-1}, pmid = {29565376}, issn = {1476-4687}, } @article {pmid29565374, year = {2018}, author = {}, title = {Children and infants must be welcome at scientific conferences, say scientist-parents.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {551}, doi = {10.1038/d41586-018-03307-0}, pmid = {29565374}, issn = {1476-4687}, } @article {pmid29565372, year = {2018}, author = {El-Showk, S and Mähönen, AP}, title = {A cellular passage to the root interior.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {454-455}, doi = {10.1038/d41586-018-02861-x}, pmid = {29565372}, issn = {1476-4687}, } @article {pmid29565371, year = {2018}, author = {Muilerman, H}, title = {Avoid vested interests in safety testing new products.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {443}, doi = {10.1038/d41586-018-03393-0}, pmid = {29565371}, issn = {1476-4687}, } @article {pmid29565370, year = {2018}, author = {Liu, RB}, title = {A diamond age of masers.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {447-449}, doi = {10.1038/d41586-018-03215-3}, pmid = {29565370}, issn = {1476-4687}, } @article {pmid29565369, year = {2018}, author = {Hurst, D}, title = {Access granted.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {S71-S72}, doi = {10.1038/d41586-018-02902-5}, pmid = {29565369}, issn = {1476-4687}, mesh = {China ; Communication Barriers ; Financing, Organized/organization & administration ; Germany ; *International Cooperation ; Japan ; Language ; Research/*organization & administration/trends ; Research Personnel/*supply & distribution ; United States ; Universities/standards ; Workforce ; }, } @article {pmid29565368, year = {2018}, author = {Castelvecchi, D}, title = {Science mourns Stephen Hawking's death.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {423-424}, doi = {10.1038/d41586-018-02957-4}, pmid = {29565368}, issn = {1476-4687}, } @article {pmid29565366, year = {2018}, author = {Chen, YE and Fischbach, MA and Belkaid, Y}, title = {Erratum: Skin microbiota-host interactions.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {543}, pmid = {29565366}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature25177.}, } @article {pmid29565365, year = {2018}, author = {Abdi-Jalebi, M and Andaji-Garmaroudi, Z and Cacovich, S and Stavrakas, C and Philippe, B and Richter, JM and Alsari, M and Booker, EP and Hutter, EM and Pearson, AJ and Lilliu, S and Savenije, TJ and Rensmo, H and Divitini, G and Ducati, C and Friend, RH and Stranks, SD}, title = {Maximizing and stabilizing luminescence from halide perovskites with potassium passivation.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {497-501}, pmid = {29565365}, issn = {1476-4687}, abstract = {Metal halide perovskites are of great interest for various high-performance optoelectronic applications. The ability to tune the perovskite bandgap continuously by modifying the chemical composition opens up applications for perovskites as coloured emitters, in building-integrated photovoltaics, and as components of tandem photovoltaics to increase the power conversion efficiency. Nevertheless, performance is limited by non-radiative losses, with luminescence yields in state-of-the-art perovskite solar cells still far from 100 per cent under standard solar illumination conditions. Furthermore, in mixed halide perovskite systems designed for continuous bandgap tunability (bandgaps of approximately 1.7 to 1.9 electronvolts), photoinduced ion segregation leads to bandgap instabilities. Here we demonstrate substantial mitigation of both non-radiative losses and photoinduced ion migration in perovskite films and interfaces by decorating the surfaces and grain boundaries with passivating potassium halide layers. We demonstrate external photoluminescence quantum yields of 66 per cent, which translate to internal yields that exceed 95 per cent. The high luminescence yields are achieved while maintaining high mobilities of more than 40 square centimetres per volt per second, providing the elusive combination of both high luminescence and excellent charge transport. When interfaced with electrodes in a solar cell device stack, the external luminescence yield-a quantity that must be maximized to obtain high efficiency-remains as high as 15 per cent, indicating very clean interfaces. We also demonstrate the inhibition of transient photoinduced ion-migration processes across a wide range of mixed halide perovskite bandgaps in materials that exhibit bandgap instabilities when unpassivated. We validate these results in fully operating solar cells. Our work represents an important advance in the construction of tunable metal halide perovskite films and interfaces that can approach the efficiency limits in tandem solar cells, coloured-light-emitting diodes and other optoelectronic applications.}, } @article {pmid29565364, year = {2018}, author = {Olalde, I and Brace, S and Allentoft, ME and Armit, I and Kristiansen, K and Booth, T and Rohland, N and Mallick, S and Szécsényi-Nagy, A and Mittnik, A and Altena, E and Lipson, M and Lazaridis, I and Harper, TK and Patterson, N and Broomandkhoshbacht, N and Diekmann, Y and Faltyskova, Z and Fernandes, D and Ferry, M and Harney, E and de Knijff, P and Michel, M and Oppenheimer, J and Stewardson, K and Barclay, A and Alt, KW and Liesau, C and Ríos, P and Blasco, C and Miguel, JV and García, RM and Fernández, AA and Bánffy, E and Bernabò-Brea, M and Billoin, D and Bonsall, C and Bonsall, L and Allen, T and Büster, L and Carver, S and Navarro, LC and Craig, OE and Cook, GT and Cunliffe, B and Denaire, A and Dinwiddy, KE and Dodwell, N and Ernée, M and Evans, C and Kuchařík, M and Farré, JF and Fowler, C and Gazenbeek, M and Pena, RG and Haber-Uriarte, M and Haduch, E and Hey, G and Jowett, N and Knowles, T and Massy, K and Pfrengle, S and Lefranc, P and Lemercier, O and Lefebvre, A and Martínez, CH and Olmo, VG and Ramírez, AB and Maurandi, JL and Majó, T and McKinley, JI and McSweeney, K and Mende, BG and Modi, A and Kulcsár, G and Kiss, V and Czene, A and Patay, R and Endrődi, A and Köhler, K and Hajdu, T and Szeniczey, T and Dani, J and Bernert, Z and Hoole, M and Cheronet, O and Keating, D and Velemínský, P and Dobeš, M and Candilio, F and Brown, F and Fernández, RF and Herrero-Corral, AM and Tusa, S and Carnieri, E and Lentini, L and Valenti, A and Zanini, A and Waddington, C and Delibes, G and Guerra-Doce, E and Neil, B and Brittain, M and Luke, M and Mortimer, R and Desideri, J and Besse, M and Brücken, G and Furmanek, M and Hałuszko, A and Mackiewicz, M and Rapiński, A and Leach, S and Soriano, I and Lillios, KT and Cardoso, JL and Pearson, MP and Włodarczak, P and Price, TD and Prieto, P and Rey, PJ and Risch, R and Guerra, MAR and Schmitt, A and Serralongue, J and Silva, AM and Smrčka, V and Vergnaud, L and Zilhão, J and Caramelli, D and Higham, T and Thomas, MG and Kennett, DJ and Fokkens, H and Heyd, V and Sheridan, A and Sjögren, KG and Stockhammer, PW and Krause, J and Pinhasi, R and Haak, W and Barnes, I and Lalueza-Fox, C and Reich, D}, title = {Erratum: The Beaker phenomenon and the genomic transformation of northwest Europe.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {543}, pmid = {29565364}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature25738.}, } @article {pmid29565363, year = {2018}, author = {Vicinanza, C and Aquila, I and Cianflone, E and Scalise, M and Marino, F and Mancuso, T and Fumagalli, F and Giovannone, ED and Cristiano, F and Iaccino, E and Marotta, P and Torella, A and Latini, R and Agosti, V and Veltri, P and Urbanek, K and Isidori, AM and Saur, D and Indolfi, C and Nadal-Ginard, B and Torella, D}, title = {Kitcre knock-in mice fail to fate-map cardiac stem cells.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {E1-E5}, pmid = {29565363}, issn = {1476-4687}, } @article {pmid29565362, year = {2018}, author = {Breeze, JD and Salvadori, E and Sathian, J and Alford, NM and Kay, CWM}, title = {Continuous-wave room-temperature diamond maser.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {493-496}, pmid = {29565362}, issn = {1476-4687}, abstract = {The maser-the microwave progenitor of the optical laser-has been confined to relative obscurity owing to its reliance on cryogenic refrigeration and high-vacuum systems. Despite this, it has found application in deep-space communications and radio astronomy owing to its unparalleled performance as a low-noise amplifier and oscillator. The recent demonstration of a room-temperature solid-state maser that utilizes polarized electron populations within the triplet states of photo-excited pentacene molecules in a p-terphenyl host paves the way for a new class of maser. However, p-terphenyl has poor thermal and mechanical properties, and the decay rates of the triplet sublevel of pentacene mean that only pulsed maser operation has been observed in this system. Alternative materials are therefore required to achieve continuous emission: inorganic materials that contain spin defects, such as diamond and silicon carbide, have been proposed. Here we report a continuous-wave room-temperature maser oscillator using optically pumped nitrogen-vacancy defect centres in diamond. This demonstration highlights the potential of room-temperature solid-state masers for use in a new generation of microwave devices that could find application in medicine, security, sensing and quantum technologies.}, } @article {pmid29565361, year = {2018}, author = {van Berlo, JH and Kanisicak, O and Maillet, M and Vagnozzi, RJ and Karch, J and Lin, SJ and Middleton, RC and Marbán, E and Molkentin, JD}, title = {van Berlo et al. reply.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {E18}, pmid = {29565361}, issn = {1476-4687}, } @article {pmid29565360, year = {2018}, author = {Reischauer, S and Stone, OA and Villasenor, A and Chi, N and Jin, SW and Martin, M and Lee, MT and Fukuda, N and Marass, M and Witty, A and Fiddes, I and Kuo, T and Chung, WS and Salek, S and Lerrigo, R and Alsiö, J and Luo, S and Tworus, D and Augustine, SM and Mucenieks, S and Nystedt, B and Giraldez, AJ and Schroth, GP and Andersson, O and Stainier, DYR}, title = {Corrigendum: Cloche is a bHLH-PAS transcription factor that drives haemato-vascular specification.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {543}, pmid = {29565360}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature18614.}, } @article {pmid29565359, year = {2018}, author = {Schiller, M and Bizzarro, M and Fernandes, VA}, title = {Isotopic evolution of the protoplanetary disk and the building blocks of Earth and the Moon.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {507-510}, pmid = {29565359}, issn = {1476-4687}, support = {616027//European Research Council/International ; }, abstract = {Nucleosynthetic isotope variability among Solar System objects is often used to probe the genetic relationship between meteorite groups and the rocky planets (Mercury, Venus, Earth and Mars), which, in turn, may provide insights into the building blocks of the Earth-Moon system. Using this approach, it has been inferred that no primitive meteorite matches the terrestrial composition and the protoplanetary disk material from which Earth and the Moon accreted is therefore largely unconstrained. This conclusion, however, is based on the assumption that the observed nucleosynthetic variability of inner-Solar-System objects predominantly reflects spatial heterogeneity. Here we use the isotopic composition of the refractory element calcium to show that the nucleosynthetic variability in the inner Solar System primarily reflects a rapid change in the mass-independent calcium isotope composition of protoplanetary disk solids associated with early mass accretion to the proto-Sun. We measure the mass-independent 48Ca/44Ca ratios of samples originating from the parent bodies of ureilite and angrite meteorites, as well as from Vesta, Mars and Earth, and find that they are positively correlated with the masses of their parent asteroids and planets, which are a proxy of their accretion timescales. This correlation implies a secular evolution of the bulk calcium isotope composition of the protoplanetary disk in the terrestrial planet-forming region. Individual chondrules from ordinary chondrites formed within one million years of the collapse of the proto-Sun reveal the full range of inner-Solar-System mass-independent 48Ca/44Ca ratios, indicating a rapid change in the composition of the material of the protoplanetary disk. We infer that this secular evolution reflects admixing of pristine outer-Solar-System material into the thermally processed inner protoplanetary disk associated with the accretion of mass to the proto-Sun. The identical calcium isotope composition of Earth and the Moon reported here is a prediction of our model if the Moon-forming impact involved protoplanets or precursors that completed their accretion near the end of the protoplanetary disk's lifetime.}, } @article {pmid29565358, year = {2018}, author = {Asadi, M and Sayahpour, B and Abbasi, P and Ngo, AT and Karis, K and Jokisaari, JR and Liu, C and Narayanan, B and Gerard, M and Yasaei, P and Hu, X and Mukherjee, A and Lau, KC and Assary, RS and Khalili-Araghi, F and Klie, RF and Curtiss, LA and Salehi-Khojin, A}, title = {A lithium-oxygen battery with a long cycle life in an air-like atmosphere.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {502-506}, pmid = {29565358}, issn = {1476-4687}, abstract = {Lithium-air batteries are considered to be a potential alternative to lithium-ion batteries for transportation applications, owing to their high theoretical specific energy. So far, however, such systems have been largely restricted to pure oxygen environments (lithium-oxygen batteries) and have a limited cycle life owing to side reactions involving the cathode, anode and electrolyte. In the presence of nitrogen, carbon dioxide and water vapour, these side reactions can become even more complex. Moreover, because of the need to store oxygen, the volumetric energy densities of lithium-oxygen systems may be too small for practical applications. Here we report a system comprising a lithium carbonate-based protected anode, a molybdenum disulfide cathode and an ionic liquid/dimethyl sulfoxide electrolyte that operates as a lithium-air battery in a simulated air atmosphere with a long cycle life of up to 700 cycles. We perform computational studies to provide insight into the operation of the system in this environment. This demonstration of a lithium-oxygen battery with a long cycle life in an air-like atmosphere is an important step towards the development of this field beyond lithium-ion technology, with a possibility to obtain much higher specific energy densities than for conventional lithium-ion batteries.}, } @article {pmid29565357, year = {2018}, author = {Zhu, B and Liu, JZ and Cauley, SF and Rosen, BR and Rosen, MS}, title = {Image reconstruction by domain-transform manifold learning.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {487-492}, pmid = {29565357}, issn = {1476-4687}, support = {U01 MH093765/MH/NIMH NIH HHS/United States ; P41 EB015896/EB/NIBIB NIH HHS/United States ; S10 RR023043/RR/NCRR NIH HHS/United States ; 1S10RR023401/NH/NIH HHS/United States ; 1S10RR019307/NH/NIH HHS/United States ; }, mesh = {Artifacts ; Image Processing, Computer-Assisted/*methods ; *Machine Learning ; Magnetic Resonance Imaging ; *Neural Networks (Computer) ; Positron-Emission Tomography ; }, abstract = {Image reconstruction is essential for imaging applications across the physical and life sciences, including optical and radar systems, magnetic resonance imaging, X-ray computed tomography, positron emission tomography, ultrasound imaging and radio astronomy. During image acquisition, the sensor encodes an intermediate representation of an object in the sensor domain, which is subsequently reconstructed into an image by an inversion of the encoding function. Image reconstruction is challenging because analytic knowledge of the exact inverse transform may not exist a priori, especially in the presence of sensor non-idealities and noise. Thus, the standard reconstruction approach involves approximating the inverse function with multiple ad hoc stages in a signal processing chain, the composition of which depends on the details of each acquisition strategy, and often requires expert parameter tuning to optimize reconstruction performance. Here we present a unified framework for image reconstruction-automated transform by manifold approximation (AUTOMAP)-which recasts image reconstruction as a data-driven supervised learning task that allows a mapping between the sensor and the image domain to emerge from an appropriate corpus of training data. We implement AUTOMAP with a deep neural network and exhibit its flexibility in learning reconstruction transforms for various magnetic resonance imaging acquisition strategies, using the same network architecture and hyperparameters. We further demonstrate that manifold learning during training results in sparse representations of domain transforms along low-dimensional data manifolds, and observe superior immunity to noise and a reduction in reconstruction artefacts compared with conventional handcrafted reconstruction methods. In addition to improving the reconstruction performance of existing acquisition methodologies, we anticipate that AUTOMAP and other learned reconstruction approaches will accelerate the development of new acquisition strategies across imaging modalities.}, } @article {pmid29564548, year = {2018}, author = {Chen, C and Sun, C and Wu, YR}, title = {The Draft Genome Sequence of a Novel High-Efficient Butanol-Producing Bacterium Clostridium Diolis Strain WST.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1011-1015}, pmid = {29564548}, issn = {1432-0991}, support = {14600601//"Sail Plan" Program for the Introduction of Outstanding Talents of Guangdong Province of China/ ; 2015KQNCX041//Major University Research Foundation of Guangdong Province of China/ ; NTF15007//Start-Up Funding of Shantou University/ ; NC2017001//International Cooperation Research Project of Shantou University/ ; GPKLMB201702//Foundation of Guangdong Provincial Key Laboratory of Marine Biotechnology/ ; }, mesh = {Acetone/*metabolism ; Alcohol Oxidoreductases/*genetics ; Base Composition ; Base Sequence ; Biofuels ; Butanols/*metabolism ; Clostridium/classification/*genetics/*metabolism ; Genome, Bacterial/*genetics ; Glucose/metabolism ; Sequence Analysis, DNA ; }, abstract = {A wild-type solventogenic strain Clostridium diolis WST, isolated from mangrove sediments, was characterized to produce high amount of butanol and acetone with negligible level of ethanol and acids from glucose via a unique acetone-butanol (AB) fermentation pathway. Through the genomic sequencing, the assembled draft genome of strain WST is calculated to be 5.85 Mb with a GC content of 29.69% and contains 5263 genes that contribute to the annotation of 5049 protein-coding sequences. Within these annotated genes, the butanol dehydrogenase gene (bdh) was determined to be in a higher amount from strain WST compared to other Clostridial strains, which is positively related to its high-efficient production of butanol. Therefore, we present a draft genome sequence analysis of strain WST in this article that should facilitate to further understand the solventogenic mechanism of this special microorganism.}, } @article {pmid29564547, year = {2018}, author = {Gao, Q and Li, X and Huang, H and Guan, Y and Mi, Q and Yao, J}, title = {The Efficacy of a Chewing Gum Containing Phyllanthus emblica Fruit Extract in Improving Oral Health.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {604-610}, pmid = {29564547}, issn = {1432-0991}, support = {2017JC05//China Tobacco Yunnan Industrial Co., Ltd Science and Technology Project/ ; 2015JC02//China Tobacco Yunnan Industrial Co., Ltd Science and Technology Project/ ; }, mesh = {Adult ; Chewing Gum/*analysis ; Female ; Food Additives/analysis/*pharmacology ; Fruit/chemistry ; Humans ; Male ; Oral Health ; Phyllanthus emblica/*chemistry ; Plant Extracts/analysis/*pharmacology ; Porphyromonas gingivalis/drug effects/growth & development ; Saliva/chemistry/microbiology ; Streptococcus mutans/drug effects/growth & development ; Young Adult ; }, abstract = {Phyllanthus emblica: (PE) fruit extract has pharmacological activity and exert anti-bacterial, anti-oxidative, anti-inflammatory and anti-cancer effects, but few study exist for evaluating its improved effects on the imbalance of oral ecology, which may contribute to series of oral diseases. In this study, an examiner-blinded, randomized, and gum-base-controlled crossover manner was conducted to evaluate the efficacy of a sugar-free chewing gum containing PE fruit extract in changing the oral microbiome. Twenty healthy young adults were randomly instructed to chew either PE gum or placebo gum. Saliva samples were collected at baseline and from 0 to 2, 2 to 5, 5 to 10, 10 to 15, and 75 to 80 min after each intervention. The following outcomes were measured: (i) salivary flow rate and pH value; (ii) total bacteria, Streptococcus mutans (S. mutans) and Porphyromonas gingivalis (P. gingivalis) counts; and (iii) volatile sulfur compound (VSC) concentrations. The results showed similar data between groups at baseline and significantly higher salivary flow rates and pH levels in the PE fruit gum group after 0-2, 2-5, and 5-10 min of chewing. Assessment of total bacteria, S. mutans, P. gingivalis, and VSC levels revealed significant differences between the PE and control gum groups at 75-80 min. No adverse effects were registered. The present finding indicated chewing gum containing PE fruit extract stimulated salivary flow and significantly reduced clinical test indexes in the short term. Chewing PE gum might be a safe means of improving oral hygiene.}, } @article {pmid29564489, year = {2018}, author = {Strange, RM and Delaney, KJ}, title = {First Report of a Mitochondrial Pseudogene in Agnathan Vertebrates (Cyclostomata: Petromyzontidae).}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {187-189}, pmid = {29564489}, issn = {1432-1432}, abstract = {We report herein the characterization of a nuclear paralog of a fragment of the mitochondrial genome (a numt) in two closely related species of lampreys (Ichthyomyzon spp.). Although numts have been characterized in several vertebrate taxa, numts have yet to be reported for fishes in general. Given the phylogenetic position of lampreys relative to other vertebrates, the presence of numts within the lamprey genome is either evidence of an ancestral trait lost in other fishes but uniquely retained in agnathans and amniotes, or (more intriguingly) a product of the genome rearrangements these animals undergo during development.}, } @article {pmid29563555, year = {2018}, author = {Klee, HJ and Tieman, DM}, title = {The genetics of fruit flavour preferences.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {347-356}, doi = {10.1038/s41576-018-0002-5}, pmid = {29563555}, issn = {1471-0064}, abstract = {Intensively bred fruit crops, including tomatoes and strawberries, are widely viewed as lacking flavour. The lack of breeder focus on the consumer is largely due to the genetic complexity of the flavour phenotype as well as a lack of a simple assay that can define consumer preferences. Rapid advances in genomics have opened up new opportunities to understand the chemistry and genetics of flavour. Here, we describe the underlying causes for the loss of flavour in fruits over time and delineate a blueprint for defining the chemistry of consumer liking, reducing that knowledge into a molecular roadmap for flavour improvement.}, } @article {pmid29563232, year = {2018}, author = {Moerman, PG and Hohenberg, PC and Vanden-Eijnden, E and Brujic, J}, title = {Emulsion patterns in the wake of a liquid-liquid phase separation front.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3599-3604}, pmid = {29563232}, issn = {1091-6490}, abstract = {Miscible liquids can phase separate in response to a composition change. In bulk fluids, the demixing begins on molecular-length scales, which coarsen into macroscopic phases. By contrast, confining a mixture in microfluidic droplets causes sequential phase separation bursts, which self-organize into rings of oil and water to make multilayered emulsions. The spacing in these nonequilibrium patterns is self-similar and scale-free over a range of droplet sizes. We develop a modified Cahn-Hilliard model, in which an immiscibility front with stretched exponential dynamics quantitatively predicts the spacing of the layers. In addition, a scaling law predicts the lifetime of each layer, giving rise to a stepwise release of inner droplets. Analogously, in long rectangular capillaries, a diffusive front yields large-scale oil and water stripes on the time scale of hours. The same theory relates their characteristic length scale to the speed of the front and the rate of mass transport. Control over liquid-liquid phase separation into large-scale patterns finds potential material applications in living cells, encapsulation, particulate design, and surface patterning.}, } @article {pmid29563231, year = {2018}, author = {Lazzarano, S and Kučka, M and Castro, JPL and Naumann, R and Medina, P and Fletcher, MNC and Wombacher, R and Gribnau, J and Hochepied, T and Van Montagu, M and Libert, C and Chan, YF}, title = {Genetic mapping of species differences via in vitro crosses in mouse embryonic stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3680-3685}, pmid = {29563231}, issn = {1091-6490}, mesh = {Animals ; Antimetabolites, Antineoplastic/pharmacology ; Biological Evolution ; Cells, Cultured ; Chromosome Mapping ; *Crosses, Genetic ; Drug Resistance/genetics ; Female ; Hybridization, Genetic ; In Vitro Techniques ; Mice ; Mice, Inbred C57BL ; Mouse Embryonic Stem Cells/*cytology/drug effects/metabolism ; Phenotype ; Pregnancy ; *Quantitative Trait Loci ; RecQ Helicases/antagonists & inhibitors ; Species Specificity ; Thioguanine/pharmacology ; }, abstract = {Discovering the genetic changes underlying species differences is a central goal in evolutionary genetics. However, hybrid crosses between species in mammals often suffer from hybrid sterility, greatly complicating genetic mapping of trait variation across species. Here, we describe a simple, robust, and transgene-free technique to generate "in vitro crosses" in hybrid mouse embryonic stem (ES) cells by inducing random mitotic cross-overs with the drug ML216, which inhibits the DNA helicase Bloom syndrome (BLM). Starting with an interspecific F1 hybrid ES cell line between the Mus musculus laboratory mouse and Mus spretus (∼1.5 million years of divergence), we mapped the genetic basis of drug resistance to the antimetabolite tioguanine to a single region containing hypoxanthine-guanine phosphoribosyltransferase (Hprt) in as few as 21 d through "flow mapping" by coupling in vitro crosses with fluorescence-activated cell sorting (FACS). We also show how our platform can enable direct study of developmental variation by rederiving embryos with contribution from the recombinant ES cell lines. We demonstrate how in vitro crosses can overcome major bottlenecks in mouse complex trait genetics and address fundamental questions in evolutionary biology that are otherwise intractable through traditional breeding due to high cost, small litter sizes, and/or hybrid sterility. In doing so, we describe an experimental platform toward studying evolutionary systems biology in mouse and potentially in human and other mammals, including cross-species hybrids.}, } @article {pmid29563230, year = {2018}, author = {Suzuki, R and Koizumi, H and Hirano, K and Kumasaka, T and Kojima, K and Tachibana, M}, title = {Analysis of oscillatory rocking curve by dynamical diffraction in protein crystals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3634-3639}, pmid = {29563230}, issn = {1091-6490}, mesh = {Aldose-Ketose Isomerases/*chemistry ; Biochemistry/*methods ; Biomechanical Phenomena ; Crystallization/*methods ; Crystallography, X-Ray/*methods ; Protein Conformation ; Streptomycetaceae/*enzymology/growth & development ; }, abstract = {High-quality protein crystals meant for structural analysis by X-ray diffraction have been grown by various methods. The observation of dynamical diffraction in protein crystals is an interesting topic because dynamical diffraction generally occurs in perfect crystals such as Si crystals. However, to our knowledge, there is no report yet on protein crystals showing clear dynamical diffraction. We wonder whether the perfection of protein crystals might still be low compared with that of high-quality Si crystals. Here, we present observations of the oscillatory profile of rocking curves for protein crystals such as glucose isomerase crystals. The oscillatory profiles are in good agreement with those predicted by the dynamical theory of diffraction. We demonstrate that dynamical diffraction occurs even in protein crystals. This suggests the possibility of the use of dynamical diffraction for the determination of the structure and charge density of proteins.}, } @article {pmid29563229, year = {2018}, author = {Woods, KJP and McDermott, JH}, title = {Schema learning for the cocktail party problem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3313-E3322}, pmid = {29563229}, issn = {1091-6490}, support = {R01 DC014739/DC/NIDCD NIH HHS/United States ; T32 DC000038/DC/NIDCD NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Attention/*physiology ; Auditory Perception/*physiology ; Cues ; Humans ; Learning/*physiology ; *Noise ; Sound Localization/*physiology ; }, abstract = {The cocktail party problem requires listeners to infer individual sound sources from mixtures of sound. The problem can be solved only by leveraging regularities in natural sound sources, but little is known about how such regularities are internalized. We explored whether listeners learn source "schemas"-the abstract structure shared by different occurrences of the same type of sound source-and use them to infer sources from mixtures. We measured the ability of listeners to segregate mixtures of time-varying sources. In each experiment a subset of trials contained schema-based sources generated from a common template by transformations (transposition and time dilation) that introduced acoustic variation but preserved abstract structure. Across several tasks and classes of sound sources, schema-based sources consistently aided source separation, in some cases producing rapid improvements in performance over the first few exposures to a schema. Learning persisted across blocks that did not contain the learned schema, and listeners were able to learn and use multiple schemas simultaneously. No learning was evident when schema were presented in the task-irrelevant (i.e., distractor) source. However, learning from task-relevant stimuli showed signs of being implicit, in that listeners were no more likely to report that sources recurred in experiments containing schema-based sources than in control experiments containing no schema-based sources. The results implicate a mechanism for rapidly internalizing abstract sound structure, facilitating accurate perceptual organization of sound sources that recur in the environment.}, } @article {pmid29563228, year = {2018}, author = {Sherry, TW}, title = {Identifying migratory birds' population bottlenecks in time and space.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3515-3517}, pmid = {29563228}, issn = {1091-6490}, mesh = {*Animal Migration ; Animals ; *Birds ; }, } @article {pmid29563227, year = {2018}, author = {Carnevale, V}, title = {Protonation underlies tonic vs. use-dependent block.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3512-3514}, pmid = {29563227}, issn = {1091-6490}, support = {R01 GM093290/GM/NIGMS NIH HHS/United States ; }, mesh = {*Anti-Arrhythmia Agents ; Hydrogenation ; *Myocardium ; }, } @article {pmid29563226, year = {2018}, author = {Leslie, HM}, title = {Value of ecosystem-based management.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3518-3520}, pmid = {29563226}, issn = {1091-6490}, mesh = {*Conservation of Natural Resources ; *Ecosystem ; }, } @article {pmid29563225, year = {2018}, author = {Tian, B and Tian, B and Smith, B and Scott, MC and Lei, Q and Hua, R and Tian, Y and Liu, Y}, title = {Facile bottom-up synthesis of partially oxidized black phosphorus nanosheets as metal-free photocatalyst for hydrogen evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4345-4350}, pmid = {29563225}, issn = {1091-6490}, abstract = {Few-layer black phosphorus (BP) nanosheets were first reported as a 2D material for the application of field-effect transistors in 2014 and have stimulated intense activity among physicists, chemists, and material and biomedical scientists, driving research into novel synthetic techniques to produce BP nanosheets. At present, exfoliation is the main route toward few-layer BP nanosheets via employing bulk BP as raw material. However, this is a complicated and time-consuming process, which is difficult for the large-scale synthesis of BP nanosheets. Moreover, BP degrades rapidly when exfoliated to nanoscale dimensions, resulting in the rapid loss of semiconducting properties. Here, we report the direct wet-chemical synthesis of few-layer BP nanosheets in gram-scale quantities in a bottom-up approach based on common laboratory reagents at low temperature, showing excellent stability due to partial oxidation of surface. Solvent and temperature are two critical factors, controlling not only the formation of BP nanosheets but also the thickness. The as-prepared BP nanosheets can extract hydrogen from pure water (pH = 6.8), exhibiting more than 24-fold higher activity than the well-known C3N4 nanosheets. Our results reporting the ability to prepare few-layer BP nanosheets with a facile, scalable, low-cost approach take us a step closer to real-world applications of phosphorene including next-generation metal-free photocatalysts for photosynthesis.}, } @article {pmid29563224, year = {2018}, author = {Zeng, Y and Shen, J and Li, B and Jiang, L}, title = {Hormone modulates protein dynamics to regulate plant growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3521-3523}, pmid = {29563224}, issn = {1091-6490}, mesh = {Arabidopsis ; Gene Expression Regulation, Plant ; *Plant Development ; *Plant Growth Regulators ; }, } @article {pmid29563223, year = {2018}, author = {Arregui, S and Iglesias, MJ and Samper, S and Marinova, D and Martin, C and Sanz, J and Moreno, Y}, title = {Data-driven model for the assessment of Mycobacterium tuberculosis transmission in evolving demographic structures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3238-E3245}, pmid = {29563223}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Child ; Child, Preschool ; Contact Tracing ; *Demography ; *Global Health ; Humans ; Infant ; Infant, Newborn ; Middle Aged ; *Models, Theoretical ; *Molecular Epidemiology ; Mycobacterium tuberculosis/*isolation & purification ; Survival Rate ; Tuberculosis/epidemiology/*mortality/*transmission ; Young Adult ; }, abstract = {In the case of tuberculosis (TB), the capabilities of epidemic models to produce quantitatively robust forecasts are limited by multiple hindrances. Among these, understanding the complex relationship between disease epidemiology and populations' age structure has been highlighted as one of the most relevant. TB dynamics depends on age in multiple ways, some of which are traditionally simplified in the literature. That is the case of the heterogeneities in contact intensity among different age strata that are common to all airborne diseases, but still typically neglected in the TB case. Furthermore, while demographic structures of many countries are rapidly aging, demographic dynamics are pervasively ignored when modeling TB spreading. In this work, we present a TB transmission model that incorporates country-specific demographic prospects and empirical contact data around a data-driven description of TB dynamics. Using our model, we find that the inclusion of demographic dynamics is followed by an increase in the burden levels predicted for the next decades in the areas of the world that are most hit by the disease today. Similarly, we show that considering realistic patterns of contacts among individuals in different age strata reshapes the transmission patterns reproduced by the models, a result with potential implications for the design of age-focused epidemiological interventions.}, } @article {pmid29562943, year = {2018}, author = {Pan, F and Zhang, L and Li, M and Hu, Y and Zeng, B and Yuan, H and Zhao, L and Zhang, C}, title = {Predominant gut Lactobacillus murinus strain mediates anti-inflammaging effects in calorie-restricted mice.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {54}, pmid = {29562943}, issn = {2049-2618}, support = {31330005, 81401141//National Natural Science Foundation of China/International ; 14YF1402200//Science and Technology Commission of Shanghai Municipality/International ; P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Aging/immunology ; Animals ; Anti-Inflammatory Agents/*metabolism ; Antigens, Bacterial/blood ; Caco-2 Cells ; Caenorhabditis elegans/physiology ; Caloric Restriction/*methods ; Cell Line, Tumor ; Cell Membrane Permeability/physiology ; Endotoxins/blood ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/*physiology ; Humans ; Inflammation/pathology ; Interleukin-8/biosynthesis ; Lactobacillus/*classification/isolation & purification ; Longevity/physiology ; Male ; Mice ; Mice, Inbred C57BL ; Tumor Necrosis Factor-alpha/blood ; }, abstract = {BACKGROUND: Calorie restriction (CR), which has a potent anti-inflammaging effect, has been demonstrated to induce dramatic changes in the gut microbiota. Whether the modulated gut microbiota contributes to the attenuation of inflammation during CR is unknown, as are the members of the microbial community that may be key mediators of this process.

RESULTS: Here, we report that a unique Lactobacillus-predominated microbial community was rapidly attained in mice within 2 weeks of CR, which decreased the levels of circulating microbial antigens and systemic inflammatory markers such as tumour necrosis factor alpha (TNF-α). Lactobacillus murinus CR147, an isolate in the most abundant operational taxonomic unit (OTU) enriched by CR, downregulated interleukin-8 production in TNF-α-stimulated Caco-2 cells and significantly increased the lifespan and the brood size of the nematode Caenorhabditis elegans. In gnotobiotic mice colonized with the gut microbiota from old mice, this strain decreased their intestinal permeability and serum endotoxin load, consequently attenuating the inflammation induced by the old microbiota.

CONCLUSIONS: Our study demonstrated that a strain of Lactobacillus murinus was promoted in CR mice and causatively contributed to the attenuation of ageing-associated inflammation.}, } @article {pmid29562936, year = {2018}, author = {Hoyles, L and Snelling, T and Umlai, UK and Nicholson, JK and Carding, SR and Glen, RC and McArthur, S}, title = {Microbiome-host systems interactions: protective effects of propionate upon the blood-brain barrier.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {55}, pmid = {29562936}, issn = {2049-2618}, support = {ARUK-PPG2016B-6//Alzheimer's Research UK/International ; MR/L01632X/1//Medical Research Council/United Kingdom ; }, mesh = {Bacteria/*metabolism ; Blood-Brain Barrier/*physiology ; Cells, Cultured ; Gastrointestinal Microbiome/*physiology ; Gastrointestinal Tract/*microbiology ; Gluconeogenesis/physiology ; Humans ; Low Density Lipoprotein Receptor-Related Protein-1/biosynthesis ; Metabolome/physiology ; NF-E2-Related Factor 2/metabolism ; Oxidative Stress/physiology ; Propionates/*metabolism ; Receptors, G-Protein-Coupled/isolation & purification ; Signal Transduction ; }, abstract = {BACKGROUND: Gut microbiota composition and function are symbiotically linked with host health and altered in metabolic, inflammatory and neurodegenerative disorders. Three recognised mechanisms exist by which the microbiome influences the gut-brain axis: modification of autonomic/sensorimotor connections, immune activation, and neuroendocrine pathway regulation. We hypothesised interactions between circulating gut-derived microbial metabolites, and the blood-brain barrier (BBB) also contribute to the gut-brain axis. Propionate, produced from dietary substrates by colonic bacteria, stimulates intestinal gluconeogenesis and is associated with reduced stress behaviours, but its potential endocrine role has not been addressed.

RESULTS: After demonstrating expression of the propionate receptor FFAR3 on human brain endothelium, we examined the impact of a physiologically relevant propionate concentration (1 μM) on BBB properties in vitro. Propionate inhibited pathways associated with non-specific microbial infections via a CD14-dependent mechanism, suppressed expression of LRP-1 and protected the BBB from oxidative stress via NRF2 (NFE2L2) signalling.

CONCLUSIONS: Together, these results suggest gut-derived microbial metabolites interact with the BBB, representing a fourth facet of the gut-brain axis that warrants further attention.}, } @article {pmid29562933, year = {2018}, author = {Ravanbakhsh, M and Sasidharan, R and Voesenek, LACJ and Kowalchuk, GA and Jousset, A}, title = {Microbial modulation of plant ethylene signaling: ecological and evolutionary consequences.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {52}, pmid = {29562933}, issn = {2049-2618}, mesh = {Bacteria/*metabolism ; Environment ; Ethylenes/*metabolism ; Gene Expression Regulation, Plant/*genetics ; Microbiota/physiology ; Plants/*microbiology ; Signal Transduction ; Stress, Physiological/physiology ; Symbiosis/*physiology ; }, abstract = {The plant hormone ethylene is one of the central regulators of plant development and stress resistance. Optimal ethylene signaling is essential for plant fitness and is under strong selection pressure. Plants upregulate ethylene production in response to stress, and this hormone triggers defense mechanisms. Due to the pleiotropic effects of ethylene, adjusting stress responses to maximize resistance, while minimizing costs, is a central determinant of plant fitness. Ethylene signaling is influenced by the plant-associated microbiome. We therefore argue that the regulation, physiology, and evolution of the ethylene signaling can best be viewed as the interactive result of plant genotype and associated microbiota. In this article, we summarize the current knowledge on ethylene signaling and recapitulate the multiple ways microorganisms interfere with it. We present ethylene signaling as a model system for holobiont-level evolution of plant phenotype: this cascade is tractable, extremely well studied from both a plant and a microbial perspective, and regulates fundamental components of plant life history. We finally discuss the potential impacts of ethylene modulation microorganisms on plant ecology and evolution. We assert that ethylene signaling cannot be fully appreciated without considering microbiota as integral regulatory actors, and we more generally suggest that plant ecophysiology and evolution can only be fully understood in the light of plant-microbiome interactions.}, } @article {pmid29562928, year = {2018}, author = {Gonzalez, E and Pitre, FE and Pagé, AP and Marleau, J and Guidi Nissim, W and St-Arnaud, M and Labrecque, M and Joly, S and Yergeau, E and Brereton, NJB}, title = {Trees, fungi and bacteria: tripartite metatranscriptomics of a root microbiome responding to soil contamination.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {53}, pmid = {29562928}, issn = {2049-2618}, mesh = {Ascomycota/genetics/growth & development/metabolism ; Basidiomycota/genetics/growth & development/metabolism ; *Biodegradation, Environmental ; Enterobacteriaceae/genetics/growth & development/metabolism ; Environmental Pollution/analysis ; Gene Expression Regulation, Bacterial/genetics ; Gene Expression Regulation, Fungal/genetics ; Gene Expression Regulation, Plant/genetics ; Glucan 1,3-beta-Glucosidase/metabolism ; Glutathione Transferase/metabolism ; Hydrocarbons/*metabolism ; Plant Roots/enzymology/*microbiology ; Salix/*metabolism/*microbiology ; Soil/chemistry ; Soil Microbiology ; Soil Pollutants/*metabolism ; Trees/microbiology ; }, abstract = {BACKGROUND: One method for rejuvenating land polluted with anthropogenic contaminants is through phytoremediation, the reclamation of land through the cultivation of specific crops. The capacity for phytoremediation crops, such as Salix spp., to tolerate and even flourish in contaminated soils relies on a highly complex and predominantly cryptic interacting community of microbial life.

METHODS: Here, Illumina HiSeq 2500 sequencing and de novo transcriptome assembly were used to observe gene expression in washed Salix purpurea cv. 'Fish Creek' roots from trees pot grown in petroleum hydrocarbon-contaminated or non-contaminated soil. All 189,849 assembled contigs were annotated without a priori assumption as to sequence origin and differential expression was assessed.

RESULTS: The 839 contigs differentially expressed (DE) and annotated from S. purpurea revealed substantial increases in transcripts encoding abiotic stress response equipment, such as glutathione S-transferases, in roots of contaminated trees as well as the hallmarks of fungal interaction, such as SWEET2 (Sugars Will Eventually Be Exported Transporter). A total of 8252 DE transcripts were fungal in origin, with contamination conditions resulting in a community shift from Ascomycota to Basidiomycota genera. In response to contamination, 1745 Basidiomycota transcripts increased in abundance (the majority uniquely expressed in contaminated soil) including major monosaccharide transporter MST1, primary cell wall and lamella CAZy enzymes, and an ectomycorrhiza-upregulated exo-β-1,3-glucanase (GH5). Additionally, 639 DE polycistronic transcripts from an uncharacterised Enterobacteriaceae species were uniformly in higher abundance in contamination conditions and comprised a wide spectrum of genes cryptic under laboratory conditions but considered putatively involved in eukaryotic interaction, biofilm formation and dioxygenase hydrocarbon degradation.

CONCLUSIONS: Fungal gene expression, representing the majority of contigs assembled, suggests out-competition of white rot Ascomycota genera (dominated by Pyronema), a sometimes ectomycorrhizal (ECM) Ascomycota (Tuber) and ECM Basidiomycota (Hebeloma) by a poorly characterised putative ECM Basidiomycota due to contamination. Root and fungal expression involved transcripts encoding carbohydrate/amino acid (C/N) dialogue whereas bacterial gene expression included the apparatus necessary for biofilm interaction and direct reduction of contamination stress, a potential bacterial currency for a role in tripartite mutualism. Unmistakable within the metatranscriptome is the degree to which the landscape of rhizospheric biology, particularly the important but predominantly uncharacterised fungal genetics, is yet to be discovered.}, } @article {pmid29562897, year = {2018}, author = {Asiche, WO and Mitalo, OW and Kasahara, Y and Tosa, Y and Mworia, EG and Owino, WO and Ushijima, K and Nakano, R and Yano, K and Kubo, Y}, title = {Comparative transcriptome analysis reveals distinct ethylene-independent regulation of ripening in response to low temperature in kiwifruit.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {47}, pmid = {29562897}, issn = {1471-2229}, support = {16H04873//Japan Society for the Promotion of Science/ ; }, mesh = {Actinidia/*genetics/*metabolism ; Ethylenes/*metabolism ; Fruit/*genetics/*metabolism ; Plant Proteins/genetics/metabolism ; Transcription Factors/genetics/metabolism ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Kiwifruit are classified as climacteric since exogenous ethylene (or its analogue propylene) induces rapid ripening accompanied by ethylene production under positive feedback regulation. However, most of the ripening-associated changes (Phase 1 ripening) in kiwifruit during storage and on-vine occur largely in the absence of any detectable ethylene. This ripening behavior is often attributed to basal levels of system I ethylene, although it is suggested to be modulated by low temperature.

RESULTS: To elucidate the mechanisms regulating Phase 1 ripening in kiwifruit, a comparative transcriptome analysis using fruit continuously exposed to propylene (at 20 °C), and during storage at 5 °C and 20 °C was conducted. Propylene exposure induced kiwifruit softening, reduction of titratable acidity (TA), increase in soluble solids content (SSC) and ethylene production within 5 days. During storage, softening and reduction of TA occurred faster in fruit at 5 °C compared to 20 °C although no endogenous ethylene production was detected. Transcriptome analysis revealed 3761 ripening-related differentially expressed genes (DEGs), of which 2742 were up-regulated by propylene while 1058 were up-regulated by low temperature. Propylene exclusively up-regulated 2112 DEGs including those associated with ethylene biosynthesis and ripening such as AcACS1, AcACO2, AcPL1, AcXET1, Acβ-GAL, AcAAT, AcERF6 and AcNAC7. Similarly, low temperature exclusively up-regulated 467 DEGS including AcACO3, AcPL2, AcPMEi, AcADH, Acβ-AMY2, AcGA2ox2, AcNAC5 and AcbZIP2 among others. A considerable number of DEGs such as AcPG, AcEXP1, AcXET2, Acβ-AMY1, AcGA2ox1, AcNAC6, AcMADS1 and AcbZIP1 were up-regulated by either propylene or low temperature. Frequent 1-MCP treatments failed to inhibit the accelerated ripening and up-regulation of associated DEGs by low temperature indicating that the changes were independent of ethylene. On-vine kiwifruit ripening proceeded in the absence of any detectable endogenous ethylene production, and coincided with increased expression of low temperature-responsive DEGs as well as the decrease in environmental temperature.

CONCLUSIONS: These results indicate that kiwifruit possess both ethylene-dependent and low temperature-modulated ripening mechanisms that are distinct and independent of each other. The current work provides a foundation for elaborating the control of these two ripening mechanisms in kiwifruit.}, } @article {pmid29562890, year = {2018}, author = {Giannoukos, G and Ciulla, DM and Marco, E and Abdulkerim, HS and Barrera, LA and Bothmer, A and Dhanapal, V and Gloskowski, SW and Jayaram, H and Maeder, ML and Skor, MN and Wang, T and Myer, VE and Wilson, CJ}, title = {UDiTaS™, a genome editing detection method for indels and genome rearrangements.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {212}, pmid = {29562890}, issn = {1471-2164}, support = {n/a//Editas Medicine/International ; }, mesh = {Antigens, Neoplasm/genetics ; Bone Neoplasms/diagnosis/genetics ; *CRISPR-Cas Systems ; Cells, Cultured ; *Gene Editing ; *Gene Rearrangement ; *Genome, Human ; Genomics/methods ; Humans ; *INDEL Mutation ; Neoplasm Proteins/antagonists & inhibitors/genetics ; Osteosarcoma/*diagnosis/genetics ; Sequence Deletion ; T-Lymphocytes/metabolism/pathology ; }, abstract = {BACKGROUND: Understanding the diversity of repair outcomes after introducing a genomic cut is essential for realizing the therapeutic potential of genomic editing technologies. Targeted PCR amplification combined with Next Generation Sequencing (NGS) or enzymatic digestion, while broadly used in the genome editing field, has critical limitations for detecting and quantifying structural variants such as large deletions (greater than approximately 100 base pairs), inversions, and translocations.

RESULTS: To overcome these limitations, we have developed a Uni-Directional Targeted Sequencing methodology, UDiTaS, that is quantitative, removes biases associated with variable-length PCR amplification, and can measure structural changes in addition to small insertion and deletion events (indels), all in a single reaction. We have applied UDiTaS to a variety of samples, including those treated with a clinically relevant pair of S. aureus Cas9 single guide RNAs (sgRNAs) targeting CEP290, and a pair of S. pyogenes Cas9 sgRNAs at T-cell relevant loci. In both cases, we have simultaneously measured small and large edits, including inversions and translocations, exemplifying UDiTaS as a valuable tool for the analysis of genome editing outcomes.

CONCLUSIONS: UDiTaS is a robust and streamlined sequencing method useful for measuring small indels as well as structural rearrangements, like translocations, in a single reaction. UDiTaS is especially useful for pre-clinical and clinical application of gene editing to measure on- and off-target editing, large and small.}, } @article {pmid29562889, year = {2018}, author = {Liao, B and Hao, Y and Lu, J and Bai, H and Guan, L and Zhang, T}, title = {Transcriptomic analysis of Perilla frutescens seed to insight into the biosynthesis and metabolic of unsaturated fatty acids.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {213}, pmid = {29562889}, issn = {1471-2164}, support = {31171588//National Natural Science Foundation of China/International ; }, mesh = {Fatty Acids, Unsaturated/*biosynthesis/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; High-Throughput Nucleotide Sequencing/*methods ; Lipid Metabolism ; Molecular Sequence Annotation ; Perilla frutescens/*genetics/growth & development/metabolism ; Plant Proteins/*genetics ; Seeds/*genetics/growth & development/metabolism ; Transcriptome ; }, abstract = {BACKGROUND: Perilla frutescens is well known for its high α-linolenic acid (ALA) accumulation in seeds and medicinal values as well as a source of edible and general-purpose oils. However, the regulatory mechanisms of the biosynthesis of fatty acid in its seeds remain poorly understood due to the lacking of sequenced genome. For better understanding the regulation of lipid metabolism and further increase its oil content or modify oil composition, time-course transcriptome and lipid composition analyses were performed.

RESULTS: Analysis of fatty acid content and composition showed that the α-linolenic acid and oleic acid accumulated rapidly from 5 DAF to 15 DAF and then kept relatively stable. However, the amount of palmitic acid and linoleic acid decreased quickly from 5 DAF to 15DAF. No significant variation of stearic acid content was observed from 5 DAF to 25DAF. Our transcriptome data analyses revealed that 110,176 unigenes were generated from six seed libraries at 5, 10, 20 DAF. Of these, 53 (31 up, 22 down) and 653 (259 up, 394 down) genes showed temporal and differentially expression during the seed development in 5 DAF vs 10 DAF, 20 vs 10 DAF, respectively. The differentially expressed genes were annotated and found to be involved in distinct functional categories and metabolic pathways. Deep mining of transcriptome data led to the identification of key genes involved in fatty acid and triacylglycerol biosynthesis and metabolism. Thirty seven members of transcription factor family AP2, B3 and NFYB putatively involved in oil synthesis and deposition were differentially expressed during seed development. The results of qRT-PCR for selected genes showed a strong positive correlation with the expression abundance measured in RNA-seq analysis.

CONCLUSIONS: The present study provides valuable genomic resources for characterizing Perilla seed gene expression at the transcriptional level and will extend our understanding of the complex molecular and cellular events of oil biosynthesis and accumulation in oilseed crops.}, } @article {pmid29562886, year = {2018}, author = {Khoder-Agha, F and Dias, JM and Comisso, M and Mirande, M}, title = {Characterization of association of human mitochondrial lysyl-tRNA synthetase with HIV-1 Pol and tRNA3Lys.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {2}, pmid = {29562886}, issn = {1471-2091}, mesh = {Animals ; Catalytic Domain ; HIV-1/*enzymology/physiology ; Humans ; Lysine-tRNA Ligase/*metabolism ; Mitochondria/*enzymology ; Protein Binding ; Protein Processing, Post-Translational ; RNA, Transfer, Lys/*metabolism ; Virus Assembly ; pol Gene Products, Human Immunodeficiency Virus/genetics/*metabolism ; }, abstract = {BACKGROUND: An important step in human immunodeficiency virus type 1 (HIV-1) replication is the packaging of tRNA3Lys from the host cell, which plays the role of primer RNA in the process of initiation of reverse transcription. The viral GagPol polyprotein precursor, and the human mitochondrial lysyl-tRNA synthetase (mLysRS) from the host cell, have been proposed to be involved in the packaging process. More specifically, the catalytic domain of mLysRS is supposed to interact with the transframe (TF or p6*) and integrase (IN) domains of the Pol region of the GagPol polyprotein.

RESULTS: In this work, we report a quantitative characterization of the protein:protein interactions between mLysRS and its viral partners, the Pol polyprotein, and the isolated integrase and transframe domains of Pol. A dissociation constant of 1.3 ± 0.2 nM was determined for the Pol:mLysRS interaction, which exemplifies the robustness of this association. The protease and reverse transcriptase domains of GagPol are dispensable in this association, but the TF and IN domains have to be connected by a linker polypeptide to recapitulate a high affinity partner for mLysRS. The binding of the viral proteins to mLysRS does not dramatically enhance the binding affinity of mLysRS for tRNA3Lys.

CONCLUSIONS: These data support the conclusion that the complex formed between GagPol, mLysRS and tRNA3Lys, which involves direct interactions between the IN and TF domains of Pol with mLysRS, is more robust than suggested by the previous models supposed to be involved in the packaging of tRNA3Lys into HIV-1 particles.}, } @article {pmid29562354, year = {2018}, author = {Cervera, H and Ambrós, S and Bernet, GP and Rodrigo, G and Elena, SF}, title = {Viral Fitness Correlates with the Magnitude and Direction of the Perturbation Induced in the Host's Transcriptome: The Tobacco Etch Potyvirus-Tobacco Case Study.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1599-1615}, pmid = {29562354}, issn = {1537-1719}, abstract = {Determining the fitness of viral genotypes has become a standard practice in virology as it is essential to evaluate their evolutionary potential. Darwinian fitness, defined as the advantage of a given genotype with respect to a reference one, is a complex property that captures, in a single figure, differences in performance at every stage of viral infection. To what extent does viral fitness result from specific molecular interactions with host factors and regulatory networks during infection? Can we identify host genes in functional classes whose expression depends on viral fitness? Here, we compared the transcriptomes of tobacco plants infected with seven genotypes of tobacco etch potyvirus that differ in fitness. We found that the larger the fitness differences among genotypes, the more dissimilar the transcriptomic profiles are. Consistently, two different mutations, one in the viral RNA polymerase and another in the viral suppressor of RNA silencing, resulted in significantly similar gene expression profiles. Moreover, we identified host genes whose expression showed a significant correlation, positive or negative, with the virus' fitness. Differentially expressed genes which were positively correlated with viral fitness activate hormone- and RNA silencing-mediated pathways of plant defense. In contrast, those that were negatively correlated with fitness affect metabolism, reducing growth, and development. Overall, these results reveal the high information content of viral fitness and suggest its potential use to predict differences in genomic profiles of infected hosts.}, } @article {pmid29562344, year = {2018}, author = {Hughes, GM and Boston, ESM and Finarelli, JA and Murphy, WJ and Higgins, DG and Teeling, EC}, title = {The Birth and Death of Olfactory Receptor Gene Families in Mammalian Niche Adaptation.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1390-1406}, pmid = {29562344}, issn = {1537-1719}, abstract = {The olfactory receptor (OR) gene families, which govern mammalian olfaction, have undergone extensive expansion and contraction through duplication and pseudogenization. Previous studies have shown that broadly defined environmental adaptations (e.g., terrestrial vs. aquatic) are correlated with the number of functional and non-functional OR genes retained. However, to date, no study has examined species-specific gene duplications in multiple phylogenetically divergent mammals to elucidate OR evolution and adaptation. Here, we identify the OR gene families driving adaptation to different ecological niches by mapping the fate of species-specific gene duplications in the OR repertoire of 94 diverse mammalian taxa, using molecular phylogenomic methods. We analyze >70,000 OR gene sequences mined from whole genomes, generated from novel amplicon sequencing data, and collated with data from previous studies, comprising one of the largest OR studies to date. For the first time, we demonstrate statistically significant patterns of OR species-specific gene duplications associated with the presence of a functioning vomeronasal organ. With respect to dietary niche, we uncover a novel link between a large number of duplications in OR family 5/8/9 and herbivory. Our results also highlight differences between social and solitary niches, indicating that a greater OR repertoire expansion may be associated with a solitary lifestyle. This study demonstrates the utility of species-specific duplications in elucidating gene family evolution, revealing how the OR repertoire has undergone expansion and contraction with respect to a number of ecological adaptations in mammals.}, } @article {pmid29562328, year = {2018}, author = {Mayali, X and Weber, PK}, title = {Quantitative isotope incorporation reveals substrate partitioning in a coastal microbial community.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy047}, pmid = {29562328}, issn = {1574-6941}, abstract = {To quantitatively link microbial identity with biogeochemical function, we carried out 14 simultaneous stable isotope probing experiments with organic and inorganic C and N substrates to measure the isotope incorporation by over one hundred co-occurring eukaryotic and prokaryotic populations in a coastal community. We found that nitrate was the most commonly incorporated substrate, and that light-driven carbon fixation was carried out by some bacterial taxa from the Flavobacteriales and OM60 (NOR5) clade, in addition to photoautotrophic phytoplankton. We found that organisms that incorporated starch, maltose, glucose, lactose and bicarbonate were phylogenetically clustered, suggesting that specific bacterial lineages specialized in the incorporation of these substrates. The data further revealed that coastal microorganisms spanned a range of resource utilization strategies from generalists to specialists and demonstrated a high level of substrate partitioning, with two thirds of taxa exhibiting unique substrate incorporation patterns and the remaining third shared by no more than three OTUs each. Specialists exhibited more extreme incorporation levels (high or low), whereas generalists displayed more intermediate activity levels. These results shed valuable insights into the bottom-up ecological strategies enabling the persistence of high microbial diversity in aquatic ecosystems.}, } @article {pmid29562238, year = {2018}, author = {Boto, E and Holmes, N and Leggett, J and Roberts, G and Shah, V and Meyer, SS and Muñoz, LD and Mullinger, KJ and Tierney, TM and Bestmann, S and Barnes, GR and Bowtell, R and Brookes, MJ}, title = {Moving magnetoencephalography towards real-world applications with a wearable system.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {657-661}, pmid = {29562238}, issn = {1476-4687}, support = {R44 HD074495/HD/NICHD NIH HHS/United States ; //Medical Research Council/United Kingdom ; 203257BARNES//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; R44 MH110288/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Drinking/physiology ; Female ; Head/physiology ; Humans ; Magnetic Fields ; Magnetoencephalography/*instrumentation/*methods ; *Movement ; Sports/physiology ; *Wearable Electronic Devices ; }, abstract = {Imaging human brain function with techniques such as magnetoencephalography typically requires a subject to perform tasks while their head remains still within a restrictive scanner. This artificial environment makes the technique inaccessible to many people, and limits the experimental questions that can be addressed. For example, it has been difficult to apply neuroimaging to investigation of the neural substrates of cognitive development in babies and children, or to study processes in adults that require unconstrained head movement (such as spatial navigation). Here we describe a magnetoencephalography system that can be worn like a helmet, allowing free and natural movement during scanning. This is possible owing to the integration of quantum sensors, which do not rely on superconducting technology, with a system for nulling background magnetic fields. We demonstrate human electrophysiological measurement at millisecond resolution while subjects make natural movements, including head nodding, stretching, drinking and playing a ball game. Our results compare well to those of the current state-of-the-art, even when subjects make large head movements. The system opens up new possibilities for scanning any subject or patient group, with myriad applications such as characterization of the neurodevelopmental connectome, imaging subjects moving naturally in a virtual environment and investigating the pathophysiology of movement disorders.}, } @article {pmid29562237, year = {2018}, author = {Zhao, EM and Zhang, Y and Mehl, J and Park, H and Lalwani, MA and Toettcher, JE and Avalos, JL}, title = {Optogenetic regulation of engineered cellular metabolism for microbial chemical production.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {683-687}, pmid = {29562237}, issn = {1476-4687}, support = {DP2 EB024247/EB/NIBIB NIH HHS/United States ; }, mesh = {Biofuels/supply & distribution ; Bioreactors/*microbiology ; Butanols/metabolism ; Darkness ; Ethanol/metabolism ; Fermentation/*radiation effects ; *Light ; Metabolic Engineering/*methods ; Metabolic Networks and Pathways/*radiation effects ; Optogenetics/*methods ; Pentanols/metabolism ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism/*radiation effects ; }, abstract = {The optimization of engineered metabolic pathways requires careful control over the levels and timing of metabolic enzyme expression. Optogenetic tools are ideal for achieving such precise control, as light can be applied and removed instantly without complex media changes. Here we show that light-controlled transcription can be used to enhance the biosynthesis of valuable products in engineered Saccharomyces cerevisiae. We introduce new optogenetic circuits to shift cells from a light-induced growth phase to a darkness-induced production phase, which allows us to control fermentation with only light. Furthermore, optogenetic control of engineered pathways enables a new mode of bioreactor operation using periodic light pulses to tune enzyme expression during the production phase of fermentation to increase yields. Using these advances, we control the mitochondrial isobutanol pathway to produce up to 8.49 ± 0.31 g l-1 of isobutanol and 2.38 ± 0.06 g l-1 of 2-methyl-1-butanol micro-aerobically from glucose. These results make a compelling case for the application of optogenetics to metabolic engineering for the production of valuable products.}, } @article {pmid29562236, year = {2018}, author = {Short, PJ and McRae, JF and Gallone, G and Sifrim, A and Won, H and Geschwind, DH and Wright, CF and Firth, HV and FitzPatrick, DR and Barrett, JC and Hurles, ME}, title = {De novo mutations in regulatory elements in neurodevelopmental disorders.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {611-616}, pmid = {29562236}, issn = {1476-4687}, support = {R01 MH110927/MH/NIMH NIH HHS/United States ; U01 MH105666/MH/NIMH NIH HHS/United States ; 098051//Wellcome Trust/United Kingdom ; K99 MH113823/MH/NIMH NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Brain/metabolism ; Conserved Sequence ; Developmental Disabilities/genetics ; Evolution, Molecular ; Exome ; Female ; Fetus/metabolism ; Humans ; Male ; *Mutation ; Neurodevelopmental Disorders/*genetics ; Regulatory Sequences, Nucleic Acid/*genetics ; }, abstract = {We previously estimated that 42% of patients with severe developmental disorders carry pathogenic de novo mutations in coding sequences. The role of de novo mutations in regulatory elements affecting genes associated with developmental disorders, or other genes, has been essentially unexplored. We identified de novo mutations in three classes of putative regulatory elements in almost 8,000 patients with developmental disorders. Here we show that de novo mutations in highly evolutionarily conserved fetal brain-active elements are significantly and specifically enriched in neurodevelopmental disorders. We identified a significant twofold enrichment of recurrently mutated elements. We estimate that, genome-wide, 1-3% of patients without a diagnostic coding variant carry pathogenic de novo mutations in fetal brain-active regulatory elements and that only 0.15% of all possible mutations within highly conserved fetal brain-active elements cause neurodevelopmental disorders with a dominant mechanism. Our findings represent a robust estimate of the contribution of de novo mutations in regulatory elements to this genetically heterogeneous set of disorders, and emphasize the importance of combining functional and evolutionary evidence to identify regulatory causes of genetic disorders.}, } @article {pmid29562235, year = {2018}, author = {Zhang, T and Niinemets, Ü and Sheffield, J and Lichstein, JW}, title = {Shifts in tree functional composition amplify the response of forest biomass to climate.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {99-102}, pmid = {29562235}, issn = {1476-4687}, mesh = {*Biodiversity ; *Biomass ; Carbon Sequestration ; *Climate Change ; Dehydration ; *Droughts/statistics & numerical data ; *Forests ; New England ; Seasons ; Southeastern United States ; Trees/*classification/growth & development/metabolism/*physiology ; Water/analysis/metabolism ; }, abstract = {Forests have a key role in global ecosystems, hosting much of the world's terrestrial biodiversity and acting as a net sink for atmospheric carbon. These and other ecosystem services that are provided by forests may be sensitive to climate change as well as climate variability on shorter time scales (for example, annual to decadal). Previous studies have documented responses of forest ecosystems to climate change and climate variability, including drought-induced increases in tree mortality rates. However, relationships between forest biomass, tree species composition and climate variability have not been quantified across a large region using systematically sampled data. Here we use systematic forest inventories from the 1980s and 2000s across the eastern USA to show that forest biomass responds to decadal-scale changes in water deficit, and that this biomass response is amplified by concurrent changes in community-mean drought tolerance, a functionally important aspect of tree species composition. The amplification of the direct effects of water stress on biomass occurs because water stress tends to induce a shift in tree species composition towards species that are more tolerant to drought but are slower growing. These results demonstrate concurrent changes in forest species composition and biomass carbon storage across a large, systematically sampled region, and highlight the potential for climate-induced changes in forest ecosystems across the world, resulting from both direct effects of climate on forest biomass and indirect effects mediated by shifts in species composition.}, } @article {pmid29562234, year = {2018}, author = {Hindupur, SK and Colombi, M and Fuhs, SR and Matter, MS and Guri, Y and Adam, K and Cornu, M and Piscuoglio, S and Ng, CKY and Betz, C and Liko, D and Quagliata, L and Moes, S and Jenoe, P and Terracciano, LM and Heim, MH and Hunter, T and Hall, MN}, title = {The protein histidine phosphatase LHPP is a tumour suppressor.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {678-682}, pmid = {29562234}, issn = {1476-4687}, support = {R01 CA194584/CA/NCI NIH HHS/United States ; CA080100/CA/NCI NIH HHS/United States ; CA082683/CA/NCI NIH HHS/United States ; CA194584/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinoma, Hepatocellular/enzymology/pathology ; Disease Models, Animal ; Histidine/*metabolism ; Humans ; Inorganic Pyrophosphatase/deficiency/genetics/*metabolism ; Liver Neoplasms/*enzymology/*pathology ; Male ; Mice ; Phosphorylation ; Proteomics ; Survival Analysis ; TOR Serine-Threonine Kinases/metabolism ; Tumor Burden ; Tumor Suppressor Proteins/deficiency/genetics/*metabolism ; }, abstract = {Histidine phosphorylation, the so-called hidden phosphoproteome, is a poorly characterized post-translational modification of proteins. Here we describe a role of histidine phosphorylation in tumorigenesis. Proteomic analysis of 12 tumours from an mTOR-driven hepatocellular carcinoma mouse model revealed that NME1 and NME2, the only known mammalian histidine kinases, were upregulated. Conversely, expression of the putative histidine phosphatase LHPP was downregulated specifically in the tumours. We demonstrate that LHPP is indeed a protein histidine phosphatase. Consistent with these observations, global histidine phosphorylation was significantly upregulated in the liver tumours. Sustained, hepatic expression of LHPP in the hepatocellular carcinoma mouse model reduced tumour burden and prevented the loss of liver function. Finally, in patients with hepatocellular carcinoma, low expression of LHPP correlated with increased tumour severity and reduced overall survival. Thus, LHPP is a protein histidine phosphatase and tumour suppressor, suggesting that deregulated histidine phosphorylation is oncogenic.}, } @article {pmid29562233, year = {2018}, author = {She, J and Guo, J and Chen, Q and Zeng, W and Jiang, Y and Bai, XC}, title = {Structural insights into the voltage and phospholipid activation of the mammalian TPC1 channel.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {130-134}, pmid = {29562233}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM079179/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Calcium Channels/chemistry/genetics/*metabolism/*ultrastructure ; *Cryoelectron Microscopy ; HEK293 Cells ; Humans ; Ion Channel Gating/*drug effects ; Mice ; Models, Molecular ; Phospholipids/chemistry/metabolism/*pharmacology ; Protein Domains/drug effects ; }, abstract = {The organellar two-pore channel (TPC) functions as a homodimer, in which each subunit contains two homologous Shaker-like six-transmembrane (6-TM)-domain repeats. TPCs belong to the voltage-gated ion channel superfamily and are ubiquitously expressed in animals and plants. Mammalian TPC1 and TPC2 are localized at the endolysosomal membrane, and have critical roles in regulating the physiological functions of these acidic organelles. Here we present electron cryo-microscopy structures of mouse TPC1 (MmTPC1)-a voltage-dependent, phosphatidylinositol 3,5-bisphosphate (PtdIns(3,5)P2)-activated Na+-selective channel-in both the apo closed state and ligand-bound open state. Combined with functional analysis, these structures provide comprehensive structural insights into the selectivity and gating mechanisms of mammalian TPC channels. The channel has a coin-slot-shaped ion pathway in the filter that defines the selectivity of mammalian TPCs. Only the voltage-sensing domain from the second 6-TM domain confers voltage dependence on MmTPC1. Endolysosome-specific PtdIns(3,5)P2 binds to the first 6-TM domain and activates the channel under conditions of depolarizing membrane potential. Structural comparisons between the apo and PtdIns(3,5)P2-bound structures show the interplay between voltage and ligand in channel activation. These MmTPC1 structures reveal lipid binding and regulation in a 6-TM voltage-gated channel, which is of interest in light of the emerging recognition of the importance of phosphoinositide regulation of ion channels.}, } @article {pmid29562232, year = {2018}, author = {Hajdinjak, M and Fu, Q and Hübner, A and Petr, M and Mafessoni, F and Grote, S and Skoglund, P and Narasimham, V and Rougier, H and Crevecoeur, I and Semal, P and Soressi, M and Talamo, S and Hublin, JJ and Gušić, I and Kućan, Ž and Rudan, P and Golovanova, LV and Doronichev, VB and Posth, C and Krause, J and Korlević, P and Nagel, S and Nickel, B and Slatkin, M and Patterson, N and Reich, D and Prüfer, K and Meyer, M and Pääbo, S and Kelso, J}, title = {Reconstructing the genetic history of late Neanderthals.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {652-656}, pmid = {29562232}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Africa/ethnology ; Animals ; Bone and Bones ; DNA, Ancient/analysis ; Europe/ethnology ; Female ; Gene Flow ; Genetics, Population ; Genome/*genetics ; Genomics ; Humans ; Hypochlorous Acid ; Male ; Neanderthals/*classification/*genetics ; *Phylogeny ; Siberia/ethnology ; Tooth ; }, abstract = {Although it has previously been shown that Neanderthals contributed DNA to modern humans, not much is known about the genetic diversity of Neanderthals or the relationship between late Neanderthal populations at the time at which their last interactions with early modern humans occurred and before they eventually disappeared. Our ability to retrieve DNA from a larger number of Neanderthal individuals has been limited by poor preservation of endogenous DNA and contamination of Neanderthal skeletal remains by large amounts of microbial and present-day human DNA. Here we use hypochlorite treatment of as little as 9 mg of bone or tooth powder to generate between 1- and 2.7-fold genomic coverage of five Neanderthals who lived around 39,000 to 47,000 years ago (that is, late Neanderthals), thereby doubling the number of Neanderthals for which genome sequences are available. Genetic similarity among late Neanderthals is well predicted by their geographical location, and comparison to the genome of an older Neanderthal from the Caucasus indicates that a population turnover is likely to have occurred, either in the Caucasus or throughout Europe, towards the end of Neanderthal history. We find that the bulk of Neanderthal gene flow into early modern humans originated from one or more source populations that diverged from the Neanderthals that were studied here at least 70,000 years ago, but after they split from a previously sequenced Neanderthal from Siberia around 150,000 years ago. Although four of the Neanderthals studied here post-date the putative arrival of early modern humans into Europe, we do not detect any recent gene flow from early modern humans in their ancestry.}, } @article {pmid29562231, year = {2018}, author = {Ghorpade, DS and Ozcan, L and Zheng, Z and Nicoloro, SM and Shen, Y and Chen, E and Blüher, M and Czech, MP and Tabas, I}, title = {Hepatocyte-secreted DPP4 in obesity promotes adipose inflammation and insulin resistance.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {673-677}, pmid = {29562231}, issn = {1476-4687}, support = {R01 HL140554/HL/NHLBI NIH HHS/United States ; R01 HL075662/HL/NHLBI NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; P01 HL087123/HL/NHLBI NIH HHS/United States ; R01 DK103047/DK/NIDDK NIH HHS/United States ; P30 DK063608/DK/NIDDK NIH HHS/United States ; R01 DK106045/DK/NIDDK NIH HHS/United States ; }, mesh = {Administration, Oral ; Animals ; Caveolin 1/deficiency/genetics/metabolism ; Dipeptidyl Peptidase 4/deficiency/genetics/*metabolism ; Factor Xa/metabolism ; Hepatocytes/drug effects/enzymology/*metabolism ; Humans ; Inflammation/*enzymology/genetics/metabolism ; *Insulin Resistance/genetics ; Intra-Abdominal Fat/metabolism/*pathology ; Macrophages/metabolism ; Male ; Mice ; Mice, Obese ; Obesity/*enzymology/genetics/metabolism ; Receptor, PAR-2/deficiency/genetics/metabolism ; Sitagliptin Phosphate/administration & dosage/pharmacology ; }, abstract = {Obesity-induced metabolic disease involves functional integration among several organs via circulating factors, but little is known about crosstalk between liver and visceral adipose tissue (VAT). In obesity, VAT becomes populated with inflammatory adipose tissue macrophages (ATMs). In obese humans, there is a close correlation between adipose tissue inflammation and insulin resistance, and in obese mice, blocking systemic or ATM inflammation improves insulin sensitivity. However, processes that promote pathological adipose tissue inflammation in obesity are incompletely understood. Here we show that obesity in mice stimulates hepatocytes to synthesize and secrete dipeptidyl peptidase 4 (DPP4), which acts with plasma factor Xa to inflame ATMs. Silencing expression of DPP4 in hepatocytes suppresses inflammation of VAT and insulin resistance; however, a similar effect is not seen with the orally administered DPP4 inhibitor sitagliptin. Inflammation and insulin resistance are also suppressed by silencing expression of caveolin-1 or PAR2 in ATMs; these proteins mediate the actions of DPP4 and factor Xa, respectively. Thus, hepatocyte DPP4 promotes VAT inflammation and insulin resistance in obesity, and targeting this pathway may have metabolic benefits that are distinct from those observed with oral DPP4 inhibitors.}, } @article {pmid29562230, year = {2018}, author = {Campos, CA and Bowen, AJ and Roman, CW and Palmiter, RD}, title = {Encoding of danger by parabrachial CGRP neurons.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {617-622}, pmid = {29562230}, issn = {1476-4687}, support = {P30 DK017047/DK/NIDDK NIH HHS/United States ; R01 DA024908/DA/NIDA NIH HHS/United States ; T32 DK007247/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Avoidance Learning/*physiology ; Calcitonin Gene-Related Peptide/*metabolism ; Calcium Signaling ; Conditioning, Classical/physiology ; Diet, High-Fat ; Electroshock ; Fear/*physiology/psychology ; Heat-Shock Response ; Lipopolysaccharides/pharmacology ; Male ; Mental Recall/physiology ; Mice ; Neurons/*metabolism ; Pain/psychology ; Parabrachial Nucleus/*cytology/physiology ; Pruritus ; Satiety Response/physiology ; }, abstract = {Animals must respond to various threats to survive. Neurons that express calcitonin gene-related peptide in the parabrachial nucleus (CGRPPBN neurons) relay sensory signals that contribute to satiation and pain-induced fear behaviour, but it is unclear how they encode these distinct processes. Here, by recording calcium transients in vivo from individual neurons in mice, we show that most CGRPPBN neurons are activated by noxious cutaneous (shock, heat, itch) and visceral stimuli (lipopolysaccharide). The same neurons are inhibited during feeding, but become activated during satiation, consistent with evidence that CGRPPBN neurons prevent overeating. CGRPPBN neurons are also activated during consumption of novel foods or by an auditory cue that has previously been paired with electrical footshocks. Correspondingly, silencing of CGRPPBN neurons attenuates the expression of food neophobia and conditioned fear responses. Therefore, in addition to transducing primary sensory danger signals, CGRPPBN neurons promote affective-behavioural states that limit harm in response to potential threats.}, } @article {pmid29562229, year = {2018}, author = {Riddle, MR and Aspiras, AC and Gaudenz, K and Peuß, R and Sung, JY and Martineau, B and Peavey, M and Box, AC and Tabin, JA and McGaugh, S and Borowsky, R and Tabin, CJ and Rohner, N}, title = {Insulin resistance in cavefish as an adaptation to a nutrient-limited environment.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {647-651}, pmid = {29562229}, issn = {1476-4687}, support = {F32 DK108495/DK/NIDDK NIH HHS/United States ; R01 HD089934/HD/NICHD NIH HHS/United States ; }, mesh = {Acclimatization/*physiology ; Aging/blood/physiology ; Animals ; Blood Glucose/metabolism ; Body Weight/genetics ; Caves ; *Ecosystem ; *Feeding Behavior ; Female ; Fishes/blood/*physiology ; Glycation End Products, Advanced/blood ; Homeostasis ; Insulin/metabolism ; *Insulin Resistance ; Male ; Mutation ; Receptor, Insulin/genetics/metabolism ; *Starvation ; }, abstract = {Periodic food shortages are a major challenge faced by organisms in natural habitats. Cave-dwelling animals must withstand long periods of nutrient deprivation, as-in the absence of photosynthesis-caves depend on external energy sources such as seasonal floods. Here we show that cave-adapted populations of the Mexican tetra, Astyanax mexicanus, have dysregulated blood glucose homeostasis and are insulin-resistant compared to river-adapted populations. We found that multiple cave populations carry a mutation in the insulin receptor that leads to decreased insulin binding in vitro and contributes to hyperglycaemia. Hybrid fish from surface-cave crosses carrying this mutation weigh more than non-carriers, and zebrafish genetically engineered to carry the mutation have increased body weight and insulin resistance. Higher body weight may be advantageous in caves as a strategy to cope with an infrequent food supply. In humans, the identical mutation in the insulin receptor leads to a severe form of insulin resistance and reduced lifespan. However, cavefish have a similar lifespan to surface fish and do not accumulate the advanced glycation end-products in the blood that are typically associated with the progression of diabetes-associated pathologies. Our findings suggest that diminished insulin signalling is beneficial in a nutrient-limited environment and that cavefish may have acquired compensatory mechanisms that enable them to circumvent the typical negative effects associated with failure to regulate blood glucose levels.}, } @article {pmid29561663, year = {2018}, author = {Shimada, T and Takagi, J and Ichino, T and Shirakawa, M and Hara-Nishimura, I}, title = {Plant Vacuoles.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {123-145}, doi = {10.1146/annurev-arplant-042817-040508}, pmid = {29561663}, issn = {1545-2123}, abstract = {Plant vacuoles are multifunctional organelles. On the one hand, most vegetative tissues develop lytic vacuoles that have a role in degradation. On the other hand, seed cells have two types of storage vacuoles: protein storage vacuoles (PSVs) in endosperm and embryonic cells and metabolite storage vacuoles in seed coats. Vacuolar proteins and metabolites are synthesized on the endoplasmic reticulum and then transported to the vacuoles via Golgi-dependent and Golgi-independent pathways. Proprotein precursors delivered to the vacuoles are converted into their respective mature forms by vacuolar processing enzyme, which also regulates various kinds of programmed cell death in plants. We summarize two types of vacuolar membrane dynamics that occur during defense responses: vacuolar membrane collapse to attack viral pathogens and fusion of vacuolar and plasma membranes to attack bacterial pathogens. We also describe the chemical defense against herbivores brought about by the presence of PSVs in the idioblast myrosin cell.}, } @article {pmid29561259, year = {2018}, author = {Sharma, A and Jani, K and Feng, GD and Karodi, P and Vemuluri, VR and Zhu, HH and Shivaji, S and Thite, V and Kajale, S and Rahi, P and Shouche, Y}, title = {Subsaxibacter sediminis sp. nov., isolated from Arctic glacial sediment and emended description of the genus Subsaxibacter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1678-1682}, doi = {10.1099/ijsem.0.002729}, pmid = {29561259}, issn = {1466-5034}, mesh = {Arctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Ice Cover/*microbiology ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/analogs & derivatives/chemistry ; Svalbard ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, yellowish-orange pigmented, rod-shaped, motile bacterium, designated strain ARC111T, was isolated from sediment of Arctic permafrost at Midtre Lovénbreen glacier, Svalbard. 16S rRNA gene based identification of strain ARC111T demonstrated highest sequence similarities to Subsaxibacter broadyi P7T (97.8 %) and Subsaxibacter arcticus JCM30334T (97.5 %) and ≤95.2 % with all other members of the family Flavobacteriaceae. Phylogenetic analysis revealed the distinct positioning of strain ARC111T within the genus Subsaxibacter. The G+C content of ARC111T was 37.8±0.5 mol% while DNA-DNA hybridization depicted 35.6 % relatedness with S. arcticus JCM30334T. Strain ARC111T had C15 : 0iso, C16 : 0iso 3-OH, C15 : 1iso G, C15 : 0anteiso, C16 : 1iso H and C17 : 0iso 3-OH as major (>5 % of the total) cellular fatty acids and MK-6 was the predominant respiratory quinone. The polar lipid profile of strain ARC111T consisted of phosphatidylethanolamine, aminolipid and an unidentified lipid. Strain ARC111T harboured sym-homospermidine as the major polyamine. Characteristic differences obtained using polyphasic analysis of strain ARC111T and its closest relatives suggested that strain ARC111T is a novel species of genus Subsaxibacter, for which the name Subsaxibacter sediminis sp. nov. has been proposed. The type strain is ARC111T (=MCC 3191T=KCTC 42965T=LMG 29783T=GDMCC 1.1201T).}, } @article {pmid29561257, year = {2018}, author = {Sung, H and Kim, HS and Lee, JY and Kang, W and Kim, PS and Hyun, DW and Tak, EJ and Jung, MJ and Yun, JH and Kim, MS and Shin, NR and Whon, TW and Rho, JR and Park, SD and Shim, HE and Bae, JW}, title = {Tumebacillus avium sp. nov., isolated from the gut of a cinereous vulture, Aegypius monachus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1659-1664}, doi = {10.1099/ijsem.0.002725}, pmid = {29561257}, issn = {1466-5034}, mesh = {Animals ; Bacillales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Falconiformes/*microbiology ; Fatty Acids/chemistry ; Gastrointestinal Tract/*microbiology ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, facultatively aerobic, spore-forming, oxidase-positive, catalase- and DNase-negative, rod-shaped and motile bacterial strain, AR23208T, was isolated from the gut of a cinereous vulture (Aegypius monachus), collected at Seoul Grand Park Zoo (Republic of Korea). Strain AR23208T grew optimally at 25-30 °C, at pH 7 and in the absence of NaCl. Phylogenetic analysis revealed that strain AR23208T shared 98.2 and 97.1 % 16S rRNA gene sequence similarity with Tumebacillus algifaecis THMBR28T and Tumebacilluslipolyticus NIO-S10T, respectively. The predominant fatty acids (>10 %) of strain AR23208T were iso-C15 : 0, summed feature 4 (anteiso-C17 : 1 B and/or iso-C17 : 1 I) and anteiso-C15 : 0 and the primary isoprenoid quinone was menaquinone-7. The polar lipids were phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol, six unidentified phospholipids, an unidentified aminophospholipid and ten unidentified lipids. The sugar components of the cell wall peptidoglycan were ribose and arabinose. The amino acids of the cell wall peptidoglycan were l-alanine, aspartic acid, meso-diaminopimelic acid, l-glutamic acid, glycine and l-lysine. The OrthoANI value based on the complete genome sequence of strain AR23208T and the closest related strain, T. algifaecis THMBR28T, was 80.4 %. The genomic DNA G+C content of strain AR23208T was 56.0 mol%. Based on the data presented in the current study, strain AR23208T is considered to represent a novel species of the genus Tumebacillus, for which the name Tumebacillus avium sp. nov. is proposed. The type strain is AR23208T (=KCTC 33929T=JCM 32188T).}, } @article {pmid29561256, year = {2018}, author = {Wang, Q and Song, Y and Choi, L and Liu, H and Wang, G and Li, M}, title = {Deinococcus rufus sp. nov., isolated from soil near an iron factory.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1622-1626}, doi = {10.1099/ijsem.0.002724}, pmid = {29561256}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Deinococcus/*classification/genetics/isolation & purification ; Extraction and Processing Industry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Iron ; Nucleic Acid Hybridization ; Parabens ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A Gram-stain-negative, non-motile, rod-shaped, red-pigmented strain, designated W37T, was isolated from soil near an iron factory in Busan (Republic of Korea). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain W37T was most closely related to Deinococcus yunweiensis YIM 007T (98.3 %) and Deinococcus radioresistens 8AT (96.3 %). The DNA-DNA relatedness between strain W37T and D. yunweiensis YIM 007T was 50.5 %. The predominant respiratory quinone was MK-8. The major polar lipids were an unidentified phosphoglycolipid, an unidentified aminophospholipid, four unidentified glycolipids, two unidentified phospholipids and an unidentified lipid. The major fatty acids (>5 %) of strain W37T were summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH), C16 : 0, C17 : 1ω8c and iso-C17 : 1ω9c. The DNA G+C content was 69.0 mol%. Moreover, the chemo-physical characteristics of strain W37T clearly differed from those of related species, including ranges of growth temperature and pH, positive activity for 4-hydroxybenzoate and negative activity for cystine arylamidase. Phenotypic, chemotaxonomic and genotypic analyses indicated that strain W37T represents a novel species of the genus Deinococcus, for which the name Deinococcus rufus sp. nov., is proposed. The type strain is W37T (=KCTC 33913T=CCTCC AB 2017081T).}, } @article {pmid29561255, year = {2018}, author = {Liu, Q and Xin, YH and Chen, XL and Liu, HC and Zhou, YG and Chen, WX}, title = {Arthrobacter ruber sp. nov., isolated from glacier ice.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1616-1621}, doi = {10.1099/ijsem.0.002719}, pmid = {29561255}, issn = {1466-5034}, mesh = {Arthrobacter/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Ice Cover/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tibet ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive strain designated MDB1-42T was isolated from ice collected from Midui glacier in Tibet, PR China. Strain MDB1-42T was catalase-positive, oxidase-negative and grew optimally at 25-28 °C and pH 7.0. Phylogenetic analysis based on 16S rRNA gene sequences revealed that MDB1-42T represented a member of the genus Arthrobacter. The highest level of 16S rRNA gene sequence similarity (99.86 %) was found with Arthrobacter agilis NBRC 15319T. Multilocus sequence analysis revealed low similarity of 91.93 % between MDB1-42T and Arthrobacter agilis NBRC 15319T. Average nucleotide identity and digital DNA-DNA hybridization values between MDB1-42T and the most closely related strain, Arthrobacter agilis DSM 20550T, were 81.36 and 24.5 %, respectively. The genomic DNA G+C content was 69.0 mol%. The major cellular fatty acids of MDB1-42T were anteiso-C15 : 0 and anteiso-C17:0. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, one unidentified glycolipid and one unidentified lipid. The predominant menaquinone was MK-9(H2). On the basis of results obtained using a polyphasic approach, a novel species Arthrobacter ruber sp. nov. is proposed, with MDB1-42T (=CGMCC 1.9772T=NBRC 113088T) as the type strain.}, } @article {pmid29561253, year = {2018}, author = {Kämpfer, P and Busse, HJ and Glaeser, SP}, title = {Novosphingobium lubricantis sp. nov., isolated from a coolant lubricant emulsion.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1560-1564}, doi = {10.1099/ijsem.0.002702}, pmid = {29561253}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Germany ; *Lubricants ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/chemistry ; Sphingomonadaceae/*classification/genetics/isolation & purification ; Ubiquinone/chemistry ; }, abstract = {A yellow-pigmented, Gram-stain-negative, rod-shaped, non-spore-forming bacterium (strain KSS165-70T) was isolated from a coolant lubricant emulsion. The 16S rRNA gene sequence analysis of strain KSS165-70T showed high sequence similarity to the type strains of Novosphingobium subterraneum (98.1 %), Novosphingobium lentum (97.9 %) and Novosphingobium taihuense (97.8 %). Sequence similarities to type strains of all other Novosphingobium species were below 97.5 %. Ubiquinone Q-10 was detected as the major respiratory quinone. The predominant fatty acid C18 : 1ω7c and the typical 2-hydroxy fatty acid C14 : 0 2-OH were detected. The polar lipid profile contained the major lipids diphosphatidylglycerol, phosphatedylethanolamine, sphingoglycolipid, phosphatidylcholine and two unidentified phospholipids. The polyamine pattern contained the major compound spermidine. Characterization by 16S rRNA gene sequence analysis, physiological parameters, pigment analysis, and ubiquinone, polar lipid and fatty acid composition revealed that strain KSS165-70T represents a new species of the genus Novosphingobium. For this reason, we propose the name Novosphingobium lubricantis sp. nov. with the type strain KSS165-70T (=CIP 111490T=CCM 8814T).}, } @article {pmid29561252, year = {2018}, author = {Chen, C and Anwar, N and Wu, C and Fu, G and Wang, R and Zhang, C and Wu, Y and Sun, C and Wu, M}, title = {Halomonas endophytica sp. nov., isolated from liquid in the stems of Populus euphratica.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1633-1638}, doi = {10.1099/ijsem.0.002585}, pmid = {29561252}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Halomonas/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Stems/microbiology ; Populus/*microbiology ; Quinones/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-negative, aerobic, motile and rod-shaped bacterium, designated MC28T, was isolated from storage liquid collected from the stems of Populus euphratica in the Xinjiang province of China. The growth range of NaCl concentration was 0.5-6.0 % (w/v), with an optimum at 3.0 % (w/v), the temperature range for growth was 10-45 °C, with an optimum at 40 °C, and the pH range for growth was 6.0-9.0, with an optimum around pH 8.5. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain MC28T formed a distinct lineage in the clade of genus Halomonas and is closely related to Halomonas desiderata DSM 9502T (96.4 %), Halomonas heilongjiangensis DSM 26881T (96.2 %) and Halomonas urumqiensis JCM 30202T (95.2 %). The average nucleotide identity, average amino acid identity and in silico DNA-DNA hybridization values between strain MC28T and the references strains were 77.2-80.3, 65.8-76.8 and 21.6-25.6 %, respectively. Chemotaxonomic analysis indicated that the main respiratory quinones were Q-9 and Q-8, the predominant cellular fatty acids were summed feature 8 (C18 : 1ω6c and/or C18 : 1ω7c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C16 : 1ω9c, C16 : 0 and C17 : 1ω9c, the major polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, phosphatidylinositol, phosphatidylinositol mannoside, an aminophospholipid, an unidentified phospholipid, an unidentified aminolipid and two unidentified lipids. Based on its phenotypic, chemotaxonomic and phylogenetic characteristics, strain MC28T is considered to represent a novel species, for which the name Halomonas endophytica sp. nov. is proposed. The type strain is MC28T (=KCTC 52999T=MCCC 1K03343T).}, } @article {pmid29560831, year = {2018}, author = {Belorkar, A and Vadigepalli, R and Wong, L}, title = {SPSNet: subpopulation-sensitive network-based analysis of heterogeneous gene expression data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {28}, pmid = {29560831}, issn = {1752-0509}, support = {R01 AA018873/AA/NIAAA NIH HHS/United States ; }, abstract = {BACKGROUND: Transcriptomic datasets often contain undeclared heterogeneity arising from biological variation such as diversity of disease subtypes, treatment subgroups, time-series gene expression, nested experimental conditions, as well as technical variation due to batch effects, platform differences in integrated meta-analyses, etc. However, current analysis approaches are primarily designed to handle comparisons between experimental conditions represented by homogeneous samples, thus precluding the discovery of underlying subphenotypes. Unsupervised methods for subtype identification are typically based on individual gene level analysis, which often result in irreproducible gene signatures for potential subtypes. Emerging methods to study heterogeneity have been largely developed in the context of single-cell datasets containing hundreds to thousands of samples, limiting their use to select contexts.

RESULTS: We present a novel analysis method, SPSNet, which identifies subtype-specific gene expression signatures based on the activity of subnetworks in biological pathways. SPSNet identifies the gene subnetworks capturing the diversity of underlying biological mechanisms, indicating potential sample subphenotypes. In the presence of extrinsic or non-biological heterogeneity (e.g. batch effects), SPSNet identifies subnetworks that are particularly affected by such variation, thus helping eliminate factors irrelevant to the biology of the phenotypes under study.

CONCLUSION: Using multiple publicly available datasets, we illustrate that SPSNet is able to consistently uncover patterns within gene expression data that correspond to meaningful heterogeneity of various origins. We also demonstrate the performance of SPSNet as a sensitive and reliable tool for understanding the structure and nature of such heterogeneity.}, } @article {pmid29560830, year = {2018}, author = {Hong, Y and Park, C and Kim, N and Cho, J and Moon, SU and Kim, J and Jeong, E and Yoon, S}, title = {QSurface: fast identification of surface expression markers in cancers.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {17}, pmid = {29560830}, issn = {1752-0509}, abstract = {BACKGROUND: Cell surface proteins have provided useful targets and biomarkers for advanced cancer therapies. The recent clinical success of antibody-drug conjugates (ADCs) highlights the importance of finding selective surface antigens for given cancer subtypes. We thus attempted to develop stand-alone software for the analysis of the cell surface transcriptome of patient cancer samples and to prioritize lineage- and/or mutation-specific over-expression markers in cancer cells.

RESULTS: A total of 519 genes were selected as surface proteins, and their expression was profiled in 14 cancer subtypes using patient sample transcriptome data. Lineage/mutation-oriented analysis was used to identify subtype-specific surface markers with statistical confidence. Experimental validation confirmed the unique over-expression of predicted surface markers (MUC4, MSLN, and SLC7A11) in lung cancer cells at the protein level. The differential cell surface gene expression of cell lines may differ from that of tissue samples due to the absence of the tumor microenvironment.

CONCLUSIONS: In the present study, advanced 3D models of lung cell lines successfully reproduced the predicted patterns, demonstrating the physiological relevance of cell line-based 3D models in validating surface markers from patient tumor data. Also QSurface software is freely available at http://compbio.sookmyung.ac.kr/~qsurface .}, } @article {pmid29560829, year = {2018}, author = {Jung, I and Kang, H and Kim, JU and Chang, H and Kim, S and Jung, W}, title = {The mRNA and miRNA transcriptomic landscape of Panax ginseng under the high ambient temperature.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {27}, pmid = {29560829}, issn = {1752-0509}, abstract = {BACKGROUND: Ginseng is a popular traditional herbal medicine in north-eastern Asia. It has been used for human health for over thousands of years. With the rise in global temperature, the production of Korean ginseng (Panax ginseng C.A.Meyer) in Korea have migrated from mid to northern parts of the Korean peninsula to escape from the various higher temperature related stresses. Under the high ambient temperature, vegetative growth was accelerated, which resulted in early flowering. This precocious phase change led to yield loss. Despite of its importance as a traditional medicine, biological mechanisms of ginseng has not been well studied and even the genome sequence of ginseng is yet to be determined due to its complex genome structure. Thus, it is challenging to investigate the molecular biology mechanisms at the transcript level.

RESULTS: To investigate how ginseng responds to the high ambient temperature environment, we performed high throughput RNA sequencing and implemented a bioinformatics pipeline for the integrated analysis of small-RNA and mRNA-seq data without a reference genome. By performing reverse transcriptase (RT) PCR and sanger sequencing of transcripts that were assembled using our pipeline, we validated that their sequences were expressed in our samples. Furthermore, to investigate the interaction between genes and non-coding small RNAs and their regulation status under the high ambient temperature, we identified potential gene regulatory miRNAs. As a result, 100,672 contigs with significant expression level were identified and 6 known, 214 conserved and 60 potential novel miRNAs were predicted to be expressed under the high ambient temperature.

CONCLUSION: Collectively, we have found that development, flowering and temperature responsive genes were induced under high ambient temperature, whereas photosynthesis related genes were repressed. Functional miRNAs were down-regulated under the high ambient temperature. Among them are miR156 and miR396 that target flowering (SPL6/9) and growth regulating genes (GRF) respectively.}, } @article {pmid29560828, year = {2018}, author = {Huang, SH and Lo, YS and Luo, YC and Tseng, YY and Yang, JM}, title = {A homologous mapping method for three-dimensional reconstruction of protein networks reveals disease-associated mutations.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {13}, pmid = {29560828}, issn = {1752-0509}, abstract = {BACKGROUND: One of the crucial steps toward understanding the associations among molecular interactions, pathways, and diseases in a cell is to investigate detailed atomic protein-protein interactions (PPIs) in the structural interactome. Despite the availability of large-scale methods for analyzing PPI networks, these methods often focused on PPI networks using genome-scale data and/or known experimental PPIs. However, these methods are unable to provide structurally resolved interaction residues and their conservations in PPI networks.

RESULTS: Here, we reconstructed a human three-dimensional (3D) structural PPI network (hDiSNet) with the detailed atomic binding models and disease-associated mutations by enhancing our PPI families and 3D-domain interologs from 60,618 structural complexes and complete genome database with 6,352,363 protein sequences across 2274 species. hDiSNet is a scale-free network (γ = 2.05), which consists of 5177 proteins and 19,239 PPIs with 5843 mutations. These 19,239 structurally resolved PPIs not only expanded the number of PPIs compared to present structural PPI network, but also achieved higher agreement with gene ontology similarities and higher co-expression correlation than the ones of 181,868 experimental PPIs recorded in public databases. Among 5843 mutations, 1653 and 790 mutations involved in interacting domains and contacting residues, respectively, are highly related to diseases. Our hDiSNet can provide detailed atomic interactions of human disease and their associated proteins with mutations. Our results show that the disease-related mutations are often located at the contacting residues forming the hydrogen bonds or conserved in the PPI family. In addition, hDiSNet provides the insights of the FGFR (EGFR)-MAPK pathway for interpreting the mechanisms of breast cancer and ErbB signaling pathway in brain cancer.

CONCLUSIONS: Our results demonstrate that hDiSNet can explore structural-based interactions insights for understanding the mechanisms of disease-associated proteins and their mutations. We believe that our method is useful to reconstruct structurally resolved PPI networks for interpreting structural genomics and disease associations.}, } @article {pmid29560827, year = {2018}, author = {Park, S and Kim, JM and Shin, W and Han, SW and Jeon, M and Jang, HJ and Jang, IS and Kang, J}, title = {BTNET : boosted tree based gene regulatory network inference algorithm using time-course measurement data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {20}, pmid = {29560827}, issn = {1752-0509}, abstract = {BACKGROUND: Identifying gene regulatory networks is an important task for understanding biological systems. Time-course measurement data became a valuable resource for inferring gene regulatory networks. Various methods have been presented for reconstructing the networks from time-course measurement data. However, existing methods have been validated on only a limited number of benchmark datasets, and rarely verified on real biological systems.

RESULTS: We first integrated benchmark time-course gene expression datasets from previous studies and reassessed the baseline methods. We observed that GENIE3-time, a tree-based ensemble method, achieved the best performance among the baselines. In this study, we introduce BTNET, a boosted tree based gene regulatory network inference algorithm which improves the state-of-the-art. We quantitatively validated BTNET on the integrated benchmark dataset. The AUROC and AUPR scores of BTNET were higher than those of the baselines. We also qualitatively validated the results of BTNET through an experiment on neuroblastoma cells treated with an antidepressant. The inferred regulatory network from BTNET showed that brachyury, a transcription factor, was regulated by fluoxetine, an antidepressant, which was verified by the expression of its downstream genes.

CONCLUSIONS: We present BTENT that infers a GRN from time-course measurement data using boosting algorithms. Our model achieved the highest AUROC and AUPR scores on the integrated benchmark dataset. We further validated BTNET qualitatively through a wet-lab experiment and showed that BTNET can produce biologically meaningful results.}, } @article {pmid29560826, year = {2018}, author = {Kwon, M and Leem, S and Yoon, J and Park, T}, title = {GxGrare: gene-gene interaction analysis method for rare variants from high-throughput sequencing data.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {19}, pmid = {29560826}, issn = {1752-0509}, support = {U01 DK085501/DK/NIDDK NIH HHS/United States ; U01 DK085524/DK/NIDDK NIH HHS/United States ; U01 DK085545/DK/NIDDK NIH HHS/United States ; U01 DK085526/DK/NIDDK NIH HHS/United States ; U01 DK085584/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: With the rapid advancement of array-based genotyping techniques, genome-wide association studies (GWAS) have successfully identified common genetic variants associated with common complex diseases. However, it has been shown that only a small proportion of the genetic etiology of complex diseases could be explained by the genetic factors identified from GWAS. This missing heritability could possibly be explained by gene-gene interaction (epistasis) and rare variants. There has been an exponential growth of gene-gene interaction analysis for common variants in terms of methodological developments and practical applications. Also, the recent advancement of high-throughput sequencing technologies makes it possible to conduct rare variant analysis. However, little progress has been made in gene-gene interaction analysis for rare variants.

RESULTS: Here, we propose GxGrare which is a new gene-gene interaction method for the rare variants in the framework of the multifactor dimensionality reduction (MDR) analysis. The proposed method consists of three steps; 1) collapsing the rare variants, 2) MDR analysis for the collapsed rare variants, and 3) detect top candidate interaction pairs. GxGrare can be used for the detection of not only gene-gene interactions, but also interactions within a single gene. The proposed method is illustrated with 1080 whole exome sequencing data of the Korean population in order to identify causal gene-gene interaction for rare variants for type 2 diabetes.

CONCLUSION: The proposed GxGrare performs well for gene-gene interaction detection with collapsing of rare variants. GxGrare is available at http://bibs.snu.ac.kr/software/gxgrare which contains simulation data and documentation. Supported operating systems include Linux and OS X.}, } @article {pmid29560825, year = {2018}, author = {Liu, FY and Hsu, TC and Choong, P and Lin, MH and Chuang, YJ and Chen, BS and Lin, C}, title = {Uncovering the regeneration strategies of zebrafish organs: a comprehensive systems biology study on heart, cerebellum, fin, and retina regeneration.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {29}, pmid = {29560825}, issn = {1752-0509}, abstract = {BACKGROUND: Regeneration is an important biological process for the restoration of organ mass, structure, and function after damage, and involves complex bio-physiological mechanisms including cell differentiation and immune responses. We constructed four regenerative protein-protein interaction (PPI) networks using dynamic models and AIC (Akaike's Information Criterion), based on time-course microarray data from the regeneration of four zebrafish organs: heart, cerebellum, fin, and retina. We extracted core and organ-specific proteins, and proposed a recalled-blastema-like formation model to uncover regeneration strategies in zebrafish.

RESULTS: It was observed that the core proteins were involved in TGF-β signaling for each step in the recalled-blastema-like formation model and TGF-β signaling may be vital for regeneration. Integrins, FGF, and PDGF accelerate hemostasis during heart injury, while Bdnf shields retinal neurons from secondary damage and augments survival during the injury response. Wnt signaling mediates the growth and differentiation of cerebellum and fin neural stem cells, potentially providing a signal to trigger differentiation.

CONCLUSION: Through our analysis of all four zebrafish regenerative PPI networks, we provide insights that uncover the underlying strategies of zebrafish organ regeneration.}, } @article {pmid29560824, year = {2018}, author = {Jeon, M and Kim, S and Park, S and Lee, H and Kang, J}, title = {In silico drug combination discovery for personalized cancer therapy.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {16}, pmid = {29560824}, issn = {1752-0509}, abstract = {BACKGROUND: Drug combination therapy, which is considered as an alternative to single drug therapy, can potentially reduce resistance and toxicity, and have synergistic efficacy. As drug combination therapies are widely used in the clinic for hypertension, asthma, and AIDS, they have also been proposed for the treatment of cancer. However, it is difficult to select and experimentally evaluate effective combinations because not only is the number of cancer drug combinations extremely large but also the effectiveness of drug combinations varies depending on the genetic variation of cancer patients. A computational approach that prioritizes the best drug combinations considering the genetic information of a cancer patient is necessary to reduce the search space.

RESULTS: We propose an in-silico method for personalized drug combination therapy discovery. We predict the synergy between two drugs and a cell line using genomic information, targets of drugs, and pharmacological information. We calculate and predict the synergy scores of 583 drug combinations for 31 cancer cell lines. For feature dimension reduction, we select the mutations or expression levels of the genes in cancer-related pathways. We also used various machine learning models. Extremely Randomized Trees (ERT), a tree-based ensemble model, achieved the best performance in the synergy score prediction regression task. The correlation coefficient between the synergy scores predicted by ERT and the actual observations is 0.738. To compare with an existing drug combination synergy classification model, we reformulate the problem as a binary classification problem by thresholding the synergy scores. ERT achieved an F1 score of 0.954 when synergy scores of 20 and -20 were used as the threshold, which is 8.7% higher than that obtained by the state-of-the-art baseline model. Moreover, the model correctly predicts the most synergistic combination, from approximately 100 candidate drug combinations, as the top choice for 15 out of the 31 cell lines. For 28 out of the 31 cell lines, the model predicts the most synergistic combination in the top 10 of approximately 100 candidate drug combinations. Finally, we analyze the results, generate synergistic rules using the features, and validate the rules through the literature survey.

CONCLUSION: Using various types of genomic information of cancer cell lines, targets of drugs, and pharmacological information, a drug combination synergy prediction pipeline is proposed. The pipeline regresses the synergy level between two drugs and a cell line as well as classifies if there exists synergy or antagonism between them. Discovering new drug combinations by our pipeline may improve personalized cancer therapy.}, } @article {pmid29560823, year = {2018}, author = {Peng, J and Zhang, X and Hui, W and Lu, J and Li, Q and Liu, S and Shang, X}, title = {Improving the measurement of semantic similarity by combining gene ontology and co-functional network: a random walk based approach.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {18}, pmid = {29560823}, issn = {1752-0509}, abstract = {BACKGROUND: Gene Ontology (GO) is one of the most popular bioinformatics resources. In the past decade, Gene Ontology-based gene semantic similarity has been effectively used to model gene-to-gene interactions in multiple research areas. However, most existing semantic similarity approaches rely only on GO annotations and structure, or incorporate only local interactions in the co-functional network. This may lead to inaccurate GO-based similarity resulting from the incomplete GO topology structure and gene annotations.

RESULTS: We present NETSIM2, a new network-based method that allows researchers to measure GO-based gene functional similarities by considering the global structure of the co-functional network with a random walk with restart (RWR)-based method, and by selecting the significant term pairs to decrease the noise information. Based on the EC number (Enzyme Commission)-based groups of yeast and Arabidopsis, evaluation test shows that NETSIM2 can enhance the accuracy of Gene Ontology-based gene functional similarity.

CONCLUSIONS: Using NETSIM2 as an example, we found that the accuracy of semantic similarities can be significantly improved after effectively incorporating the global gene-to-gene interactions in the co-functional network, especially on the species that gene annotations in GO are far from complete.}, } @article {pmid29560822, year = {2018}, author = {Mishra, P and Lee, NR and Lakshmanan, M and Kim, M and Kim, BG and Lee, DY}, title = {Genome-scale model-driven strain design for dicarboxylic acid production in Yarrowia lipolytica.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {12}, pmid = {29560822}, issn = {1752-0509}, abstract = {BACKGROUND: Recently, there have been several attempts to produce long-chain dicarboxylic acids (DCAs) in various microbial hosts. Of these, Yarrowia lipolytica has great potential due to its oleaginous characteristics and unique ability to utilize hydrophobic substrates. However, Y. lipolytica should be further engineered to make it more competitive: the current approaches are mostly intuitive and cumbersome, thus limiting its industrial application.

RESULTS: In this study, we proposed model-guided metabolic engineering strategies for enhanced production of DCAs in Y. lipolytica. At the outset, we reconstructed genome-scale metabolic model (GSMM) of Y. lipolytica (iYLI647) by substantially expanding the previous models. Subsequently, the model was validated using three sets of published culture experiment data. It was finally exploited to identify genetic engineering targets for overexpression, knockout, and cofactor modification by applying several in silico strain design methods, which potentially give rise to high yield production of the industrially relevant long-chain DCAs, e.g., dodecanedioic acid (DDDA). The resultant targets include (1) malate dehydrogenase and malic enzyme genes and (2) glutamate dehydrogenase gene, in silico overexpression of which generated additional NADPH required for fatty acid synthesis, leading to the increased DDDA fluxes by 48% and 22% higher, respectively, compared to wild-type. We further investigated the effect of supplying branched-chain amino acids on the acetyl-CoA turn-over rate which is key metabolite for fatty acid synthesis, suggesting their significance for production of DDDA in Y. lipolytica.

CONCLUSION: In silico model-based strain design strategies allowed us to identify several metabolic engineering targets for overproducing DCAs in lipid accumulating yeast, Y. lipolytica. Thus, the current study can provide a methodological framework that is applicable to other oleaginous yeasts for value-added biochemical production.}, } @article {pmid29560821, year = {2018}, author = {Mori, H and Maruyama, T and Yano, M and Yamada, T and Kurokawa, K}, title = {VITCOMIC2: visualization tool for the phylogenetic composition of microbial communities based on 16S rRNA gene amplicons and metagenomic shotgun sequencing.}, journal = {BMC systems biology}, volume = {12}, number = {Suppl 2}, pages = {30}, pmid = {29560821}, issn = {1752-0509}, abstract = {BACKGROUND: The 16S rRNA gene-based amplicon sequencing analysis is widely used to determine the taxonomic composition of microbial communities. Once the taxonomic composition of each community is obtained, evolutionary relationships among taxa are inferred by a phylogenetic tree. Thus, the combined representation of taxonomic composition and phylogenetic relationships among taxa is a powerful method for understanding microbial community structure; however, applying phylogenetic tree-based representation with information on the abundance of thousands or more taxa in each community is a difficult task. For this purpose, we previously developed the tool VITCOMIC (VIsualization tool for Taxonomic COmpositions of MIcrobial Community), which is based on the genome-sequenced microbes' phylogenetic information. Here, we introduce VITCOMIC2, which incorporates substantive improvements over VITCOMIC that were necessary to address several issues associated with 16S rRNA gene-based analysis of microbial communities.

RESULTS: We developed VITCOMIC2 to provide (i) sequence identity searches against broad reference taxa including uncultured taxa; (ii) normalization of 16S rRNA gene copy number differences among taxa; (iii) rapid sequence identity searches by applying the graphics processing unit-based sequence identity search tool CLAST; (iv) accurate taxonomic composition inference and nearly full-length 16S rRNA gene sequence reconstructions for metagenomic shotgun sequencing; and (v) an interactive user interface for simultaneous representation of the taxonomic composition of microbial communities and phylogenetic relationships among taxa. We validated the accuracy of processes (ii) and (iv) by using metagenomic shotgun sequencing data from a mock microbial community.

CONCLUSIONS: The improvements incorporated into VITCOMIC2 enable users to acquire an intuitive understanding of microbial community composition based on the 16S rRNA gene sequence data obtained from both metagenomic shotgun and amplicon sequencing.}, } @article {pmid29559693, year = {2018}, author = {Zengini, E and Hatzikotoulas, K and Tachmazidou, I and Steinberg, J and Hartwig, FP and Southam, L and Hackinger, S and Boer, CG and Styrkarsdottir, U and Gilly, A and Suveges, D and Killian, B and Ingvarsson, T and Jonsson, H and Babis, GC and McCaskie, A and Uitterlinden, AG and van Meurs, JBJ and Thorsteinsdottir, U and Stefansson, K and Davey Smith, G and Wilkinson, JM and Zeggini, E}, title = {Genome-wide analyses using UK Biobank data provide insights into the genetic architecture of osteoarthritis.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {549-558}, pmid = {29559693}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Osteoarthritis is a common complex disease imposing a large public-health burden. Here, we performed a genome-wide association study for osteoarthritis, using data across 16.5 million variants from the UK Biobank resource. After performing replication and meta-analysis in up to 30,727 cases and 297,191 controls, we identified nine new osteoarthritis loci, in all of which the most likely causal variant was noncoding. For three loci, we detected association with biologically relevant radiographic endophenotypes, and in five signals we identified genes that were differentially expressed in degraded compared with intact articular cartilage from patients with osteoarthritis. We established causal effects on osteoarthritis for higher body mass index but not for triglyceride levels or genetic predisposition to type 2 diabetes.}, } @article {pmid29559534, year = {2018}, author = {Lu, Z and Sethu, R and Imlay, JA}, title = {Endogenous superoxide is a key effector of the oxygen sensitivity of a model obligate anaerobe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3266-E3275}, pmid = {29559534}, issn = {1091-6490}, support = {R01 GM049640/GM/NIGMS NIH HHS/United States ; R37 GM049640/GM/NIGMS NIH HHS/United States ; }, mesh = {Anaerobiosis ; Bacterial Proteins/genetics/*metabolism ; Bacteroides thetaiotaomicron/genetics/*metabolism ; Escherichia coli/genetics/*metabolism ; Oxidative Stress ; Oxygen/*metabolism ; Superoxides/*metabolism ; }, abstract = {It has been unclear whether superoxide and/or hydrogen peroxide play important roles in the phenomenon of obligate anaerobiosis. This question was explored using Bacteroides thetaiotaomicron, a major fermentative bacterium in the human gastrointestinal tract. Aeration inactivated two enzyme families-[4Fe-4S] dehydratases and nonredox mononuclear iron enzymes-whose homologs, in contrast, remain active in aerobic Escherichia coli Inactivation-rate measurements of one such enzyme, B. thetaiotaomicron fumarase, showed that it is no more intrinsically sensitive to oxidants than is an E. coli fumarase. Indeed, when the E. coli enzymes were expressed in B. thetaiotaomicron, they no longer could tolerate aeration; conversely, the B. thetaiotaomicron enzymes maintained full activity when expressed in aerobic E. coli Thus, the aerobic inactivation of the B. thetaiotaomicron enzymes is a feature of their intracellular environment rather than of the enzymes themselves. B. thetaiotaomicron possesses superoxide dismutase and peroxidases, and it can repair damaged enzymes. However, measurements confirmed that the rate of reactive oxygen species production inside aerated B. thetaiotaomicron is far higher than in E. coli Analysis of the damaged enzymes recovered from aerated B. thetaiotaomicron suggested that they had been inactivated by superoxide rather than by hydrogen peroxide. Accordingly, overproduction of superoxide dismutase substantially protected the enzymes from aeration. We conclude that when this anaerobe encounters oxygen, its internal superoxide levels rise high enough to inactivate key catabolic and biosynthetic enzymes. Superoxide thus comprises a major element of the oxygen sensitivity of this anaerobe. The extent to which molecular oxygen exerts additional direct effects remains to be determined.}, } @article {pmid29559533, year = {2018}, author = {Greicius, G and Kabiri, Z and Sigmundsson, K and Liang, C and Bunte, R and Singh, MK and Virshup, DM}, title = {PDGFRα+ pericryptal stromal cells are the critical source of Wnts and RSPO3 for murine intestinal stem cells in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3173-E3181}, pmid = {29559533}, issn = {1091-6490}, mesh = {Acyltransferases/physiology ; Animals ; Cell Differentiation ; Cell Proliferation ; Epithelial Cells/*cytology/metabolism ; Homeostasis ; Intestinal Mucosa/metabolism ; Intestines/*cytology ; Membrane Proteins/physiology ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Organoids/cytology/metabolism ; Receptor, Platelet-Derived Growth Factor alpha/*physiology ; Stem Cell Niche/*physiology ; Stem Cells/*cytology/metabolism ; Stromal Cells/*cytology/metabolism ; Thrombospondins/genetics/*metabolism ; Wnt1 Protein/genetics/*metabolism ; }, abstract = {Wnts and R-spondins (RSPOs) support intestinal homeostasis by regulating crypt cell proliferation and differentiation. Ex vivo, Wnts secreted by Paneth cells in organoids can regulate the proliferation and differentiation of Lgr5-expressing intestinal stem cells. However, in vivo, Paneth cell and indeed all epithelial Wnt production is completely dispensable, and the cellular source of Wnts and RSPOs that maintain the intestinal stem-cell niche is not known. Here we investigated both the source and the functional role of stromal Wnts and RSPO3 in regulation of intestinal homeostasis. RSPO3 is highly expressed in pericryptal myofibroblasts in the lamina propria and is several orders of magnitude more potent than RSPO1 in stimulating both Wnt/β-catenin signaling and organoid growth. Stromal Rspo3 ablation ex vivo resulted in markedly decreased organoid growth that was rescued by exogenous RSPO3 protein. Pdgf receptor alpha (PdgfRα) is known to be expressed in pericryptal myofibroblasts. We therefore evaluated if PdgfRα identified the key stromal niche cells. In vivo, Porcn excision in PdgfRα+ cells blocked intestinal crypt formation, demonstrating that Wnt production in the stroma is both necessary and sufficient to support the intestinal stem-cell niche. Mice with Rspo3 excision in the PdgfRα+ cells had decreased intestinal crypt Wnt/β-catenin signaling and Paneth cell differentiation and were hypersensitive when stressed with dextran sodium sulfate. The data support a model of the intestinal stem-cell niche regulated by both Wnts and RSPO3 supplied predominantly by stromal pericryptal myofibroblasts marked by PdgfRα.}, } @article {pmid29559532, year = {2018}, author = {Liu, Y and Liu, Y and Wu, J and Roizman, B and Zhou, GG}, title = {Innate responses to gene knockouts impact overlapping gene networks and vary with respect to resistance to viral infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3230-E3237}, pmid = {29559532}, issn = {1091-6490}, mesh = {Biomarkers/*analysis ; Gene Expression Regulation ; Gene Knockout Techniques ; *Gene Regulatory Networks ; Herpes Simplex/genetics/*immunology/virology ; Herpesvirus 1, Human/*immunology ; Humans ; Immunity, Innate/*genetics ; Laryngeal Neoplasms/genetics/*immunology/virology ; Tumor Cells, Cultured ; Virus Replication/*genetics ; }, abstract = {Analyses of the levels of mRNAs encoding IFIT1, IFI16, RIG-1, MDA5, CXCL10, LGP2, PUM1, LSD1, STING, and IFNβ in cell lines from which the gene encoding LGP2, LSD1, PML, HDAC4, IFI16, PUM1, STING, MDA5, IRF3, or HDAC 1 had been knocked out, as well as the ability of these cell lines to support the replication of HSV-1, revealed the following: (i) Cell lines lacking the gene encoding LGP2, PML, or HDAC4 (cluster 1) exhibited increased levels of expression of partially overlapping gene networks. Concurrently, these cell lines produced from 5 fold to 12 fold lower yields of HSV-1 than the parental cells. (ii) Cell lines lacking the genes encoding STING, LSD1, MDA5, IRF3, or HDAC 1 (cluster 2) exhibited decreased levels of mRNAs of partially overlapping gene networks. Concurrently, these cell lines produced virus yields that did not differ from those produced by the parental cell line. The genes up-regulated in cell lines forming cluster 1, overlapped in part with genes down-regulated in cluster 2. The key conclusions are that gene knockouts and subsequent selection for growth causes changes in expression of multiple genes, and hence the phenotype of the cell lines cannot be ascribed to a single gene; the patterns of gene expression may be shared by multiple knockouts; and the enhanced immunity to viral replication by cluster 1 knockout cell lines but not by cluster 2 cell lines suggests that in parental cells, the expression of innate resistance to infection is specifically repressed.}, } @article {pmid29559531, year = {2018}, author = {Gournas, C and Gkionis, S and Carquin, M and Twyffels, L and Tyteca, D and André, B}, title = {Conformation-dependent partitioning of yeast nutrient transporters into starvation-protective membrane domains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3145-E3154}, pmid = {29559531}, issn = {1091-6490}, mesh = {Amino Acid Transport Systems, Basic/*chemistry/*metabolism ; Cell Membrane/*metabolism ; Endocytosis/*physiology ; *Food ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Molecular Conformation ; Saccharomyces cerevisiae/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/*metabolism ; Sphingolipids/metabolism ; *Starvation ; Ubiquitination ; }, abstract = {The eukaryotic plasma membrane is compartmentalized into domains enriched in specific lipids and proteins. However, our understanding of the molecular bases and biological roles of this partitioning remains incomplete. The best-studied domain in yeast is the membrane compartment containing the arginine permease Can1 (MCC) and later found to cluster additional transporters. MCCs correspond to static, furrow-like invaginations of the plasma membrane and associate with subcortical structures named "eisosomes" that include upstream regulators of the target of rapamycin complex 2 (TORC2) in the sensing of sphingolipids and membrane stress. However, how and why Can1 and other nutrient transporters preferentially segregate in MCCs remains unknown. In this study we report that the clustering of Can1 in MCCs is dictated by its conformation, requires proper sphingolipid biosynthesis, and controls its ubiquitin-dependent endocytosis. In the substrate-free outward-open conformation, Can1 accumulates in MCCs in a manner dependent on sustained biogenesis of complex sphingolipids. An arginine transport-elicited shift to an inward-facing conformation promotes its cell-surface dissipation and makes it accessible to the ubiquitylation machinery triggering its endocytosis. We further show that under starvation conditions MCCs increase in number and size, this being dependent on the BAR domain-containing Lsp1 eisosome component. This expansion of MCCs provides protection for nutrient transporters from bulk endocytosis occurring in parallel with autophagy upon TORC1 inhibition. Our study reveals nutrient-regulated protection from endocytosis as an important role for protein partitioning into membrane domains.}, } @article {pmid29559530, year = {2018}, author = {Ratan Murty, NA and Arun, SP}, title = {Multiplicative mixing of object identity and image attributes in single inferior temporal neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3276-E3285}, pmid = {29559530}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 500027-Z-09-Z//Wellcome Trust-DBT India Alliance/India ; }, mesh = {Animals ; Behavior, Animal ; *Computer Simulation ; Form Perception/*physiology ; Macaca radiata ; Neural Networks (Computer) ; Neurons/*physiology ; Pattern Recognition, Visual/*physiology ; Photic Stimulation ; Temporal Lobe/*physiology ; Visual Perception/*physiology ; }, abstract = {Object recognition is challenging because the same object can produce vastly different images, mixing signals related to its identity with signals due to its image attributes, such as size, position, rotation, etc. Previous studies have shown that both signals are present in high-level visual areas, but precisely how they are combined has remained unclear. One possibility is that neurons might encode identity and attribute signals multiplicatively so that each can be efficiently decoded without interference from the other. Here, we show that, in high-level visual cortex, responses of single neurons can be explained better as a product rather than a sum of tuning for object identity and tuning for image attributes. This subtle effect in single neurons produced substantially better population decoding of object identity and image attributes in the neural population as a whole. This property was absent both in low-level vision models and in deep neural networks. It was also unique to invariances: when tested with two-part objects, neural responses were explained better as a sum than as a product of part tuning. Taken together, our results indicate that signals requiring separate decoding, such as object identity and image attributes, are combined multiplicatively in IT neurons, whereas signals that require integration (such as parts in an object) are combined additively.}, } @article {pmid29559529, year = {2018}, author = {Avino, TA and Barger, N and Vargas, MV and Carlson, EL and Amaral, DG and Bauman, MD and Schumann, CM}, title = {Neuron numbers increase in the human amygdala from birth to adulthood, but not in autism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3710-3715}, pmid = {29559529}, issn = {1091-6490}, support = {T32 MH073124/MH/NIMH NIH HHS/United States ; U54 HD079125/HD/NICHD NIH HHS/United States ; R37 MH041479/MH/NIMH NIH HHS/United States ; R01 MH097236/MH/NIMH NIH HHS/United States ; R01 MH041479/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Amygdala/*physiopathology ; Autistic Disorder/*pathology ; Case-Control Studies ; Cells, Cultured ; Child ; Child, Preschool ; Cohort Studies ; Female ; Humans ; Male ; Neurons/*cytology/physiology ; Young Adult ; }, abstract = {Remarkably little is known about the postnatal cellular development of the human amygdala. It plays a central role in mediating emotional behavior and has an unusually protracted development well into adulthood, increasing in size by 40% from youth to adulthood. Variation from this typical neurodevelopmental trajectory could have profound implications on normal emotional development. We report the results of a stereological analysis of the number of neurons in amygdala nuclei of 52 human brains ranging from 2 to 48 years of age [24 neurotypical and 28 autism spectrum disorder (ASD)]. In neurotypical development, the number of mature neurons in the basal and accessory basal nuclei increases from childhood to adulthood, coinciding with a decrease of immature neurons within the paralaminar nucleus. Individuals with ASD, in contrast, show an initial excess of amygdala neurons during childhood, followed by a reduction in adulthood across nuclei. We propose that there is a long-term contribution of mature neurons from the paralaminar nucleus to other nuclei of the neurotypical human amygdala and that this growth trajectory may be altered in ASD, potentially underlying the volumetric changes detected in ASD and other neurodevelopmental or neuropsychiatric disorders.}, } @article {pmid29559528, year = {2018}, author = {Gilbert, OM}, title = {Altruism or association?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3069-E3070}, pmid = {29559528}, issn = {1091-6490}, mesh = {*Altruism ; *Biological Evolution ; }, } @article {pmid29559527, year = {2018}, author = {Wang, C and Lu, X}, title = {Reply to Gilbert: On the relationship between association and altruism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3071-E3072}, pmid = {29559527}, issn = {1091-6490}, mesh = {*Altruism ; }, } @article {pmid29559526, year = {2018}, author = {Lee, CK and de Anda, J and Baker, AE and Bennett, RR and Luo, Y and Lee, EY and Keefe, JA and Helali, JS and Ma, J and Zhao, K and Golestanian, R and O'Toole, GA and Wong, GCL}, title = {Multigenerational memory and adaptive adhesion in early bacterial biofilm communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {4471-4476}, pmid = {29559526}, issn = {1091-6490}, support = {R37 AI083256/AI/NIAID NIH HHS/United States ; T32 GM008042/GM/NIGMS NIH HHS/United States ; U54 CA193417/CA/NCI NIH HHS/United States ; R01 AI102584/AI/NIAID NIH HHS/United States ; T32 GM008185/GM/NIGMS NIH HHS/United States ; T32 AR071307/AR/NIAMS NIH HHS/United States ; }, mesh = {Bacterial Adhesion/*physiology ; Biofilms/*growth & development ; Cyclic AMP/*metabolism ; Fimbriae, Bacterial/*physiology ; Pseudomonas aeruginosa/*physiology ; Second Messenger Systems/*physiology ; }, abstract = {Using multigenerational, single-cell tracking we explore the earliest events of biofilm formation by Pseudomonas aeruginosa During initial stages of surface engagement (≤20 h), the surface cell population of this microbe comprises overwhelmingly cells that attach poorly (∼95% stay <30 s, well below the ∼1-h division time) with little increase in surface population. If we harvest cells previously exposed to a surface and direct them to a virgin surface, we find that these surface-exposed cells and their descendants attach strongly and then rapidly increase the surface cell population. This "adaptive," time-delayed adhesion requires determinants we showed previously are critical for surface sensing: type IV pili (TFP) and cAMP signaling via the Pil-Chp-TFP system. We show that these surface-adapted cells exhibit damped, coupled out-of-phase oscillations of intracellular cAMP levels and associated TFP activity that persist for multiple generations, whereas surface-naïve cells show uncorrelated cAMP and TFP activity. These correlated cAMP-TFP oscillations, which effectively impart intergenerational memory to cells in a lineage, can be understood in terms of a Turing stochastic model based on the Pil-Chp-TFP framework. Importantly, these cAMP-TFP oscillations create a state characterized by a suppression of TFP motility coordinated across entire lineages and lead to a drastic increase in the number of surface-associated cells with near-zero translational motion. The appearance of this surface-adapted state, which can serve to define the historical classification of "irreversibly attached" cells, correlates with family tree architectures that facilitate exponential increases in surface cell populations necessary for biofilm formation.}, } @article {pmid29559245, year = {2018}, author = {Testo, W and Øllgaard, B and Field, A and Almeida, T and Kessler, M and Barrington, D}, title = {Phylogenetic systematics, morphological evolution, and natural groups in neotropical Phlegmariurus (Lycopodiaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {1-13}, doi = {10.1016/j.ympev.2018.03.016}, pmid = {29559245}, issn = {1095-9513}, mesh = {Biodiversity ; Brazil ; Likelihood Functions ; Lycopodiaceae/*anatomy & histology/*classification ; *Phylogeny ; Plant Leaves/anatomy & histology ; Plant Stems/anatomy & histology ; Species Specificity ; *Tropical Climate ; }, abstract = {The Neotropical clade of the lycophyte genus Phlegmariurus is comprised of an estimated 150 described species and exhibits exceptional morphological and ecological diversity. Because of their simple morphology, frequent convergent evolution, and the recentness of the group's diversification, the delimitation of species and species groups has remained challenging. Here, we present a robustly support phylogeny of Neotropical Phlegmariurus based on six chloroplast markers and ca. 70% of known species, and use ancestral character state reconstruction to investigate morphological evolution in the clade, and define natural species groups. The Neotropical species of Phlegmariurus form a clade that also includes a small number of Afro-Madagascan species. A morphologically and ecologically variable group of species from southeastern Brazil form a monophyletic group and represent a parallel radiation to principally Andean lineages. Species groups in Neotropical Phlegmariurus that were previously recognized based on morphology are not monophyletic. We find support for 11 morphologically cohesive and well-supported species groups. Morphological homoplasy is common in Phlegmariurus and complicates infrageneric classification of the Neotropical taxa. Our results provide a useful framework for identifying species groups and understanding patterns of morphological evolution in Neotropical Phlegmariurus. The radiation of the Brazilian species remains poorly understood and requires further study.}, } @article {pmid29559085, year = {2018}, author = {Buchrieser, C and Mecsas, J}, title = {Editorial overview: Host-pathogen interactions shaped through evolutionary and regulatory processes.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {v-viii}, doi = {10.1016/j.mib.2018.02.001}, pmid = {29559085}, issn = {1879-0364}, } @article {pmid29558994, year = {2018}, author = {Mullaney, JA and Stephens, JE and Costello, ME and Fong, C and Geeling, BE and Gavin, PG and Wright, CM and Spector, TD and Brown, MA and Hamilton-Williams, EE}, title = {Correction to: Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {51}, pmid = {29558994}, issn = {2049-2618}, abstract = {Following publication of the original article [1] it came to the attention of the Production Editor that Figs. 1 and 2 had not been replaced with the newly revised figures supplied by the authors (the originals being unusable due to poor quality image and text).}, } @article {pmid29558977, year = {2018}, author = {Godakanda, I and Abeysena, C and Lokubalasooriya, A}, title = {Sedentary behavior during leisure time, physical activity and dietary habits as risk factors of overweight among school children aged 14-15 years: case control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {186}, pmid = {29558977}, issn = {1756-0500}, mesh = {Adolescent ; Body Mass Index ; Case-Control Studies ; Exercise/*physiology ; Feeding Behavior/*physiology ; Female ; Health Surveys/methods/statistics & numerical data ; Humans ; *Leisure Activities ; Logistic Models ; Male ; Overweight/*physiopathology ; Risk Factors ; Schools ; *Sedentary Behavior ; Sri Lanka ; }, abstract = {OBJECTIVE: To determine the risk of sedentary behavior during leisure time, physical activity and dietary habits on overweight among school children aged 14-15 years in Kalutara District, Sri Lanka.

RESULTS: School based case-control study was conducted during September to November 2013 including 176 overweight children as cases and 704 children with normal weight as controls. Cases were defined as body mass index for age and sex of ≥ +1SD and controls as those in the range of -2SD to +1SD. Validated instruments were used for data collection. Multiple logistic regression was applied and results were expressed with adjusted odds ratios (OR) and 95% confidence intervals (CI). Risk factors for overweight were insufficient physical activity (OR 1.6, 95% CI 1.1-2.4), watching video/DVD ≥ 2 h (OR 3.1, 95% CI 1.8-5.3), watching television ≥ 2 h (OR 2.6, 95% CI 1.7-3.8) and doing homework ≥ 2 h, (OR 1.8, 95% CI 1.2-2.7). Consuming meat (OR 1.9, 95% CI 1.2-3.1), fish or other sea foods (OR 1.6, 95% CI 1.1-2.8), fast food/fried rice/oily foods (OR 1.9, 95% CI 1.2-2.9), carbonated drinks or sugary drinks (OR 1.9, 95% CI 1.2-2.8), sweets, cookies or ice cream (OR 1.8, 95% CI 1.2-2.9) were dietary risk factors for overweight. Consuming legumes and seeds (OR 0.50, 95% CI 0.3-0.7), vegetables and fruits (OR 0.6, 95% CI 0.4-0.9) were protective factors for overweight.}, } @article {pmid29558936, year = {2018}, author = {Tang, S and Zhang, Y and Zhai, X and Wilkes, A and Wang, C and Wang, K}, title = {Effect of grazing on methane uptake from Eurasian steppe of China.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {11}, pmid = {29558936}, issn = {1472-6785}, support = {2016BS0320//Natural Science Foundation of Inner Mongolia/International ; 29015122//National Scientific Research Institutions to Important Agricultural Extension Service Pilot in Hebei Province -Northern Ecology Function Area/International ; 31772654//National Natural Science Foundation/International ; }, abstract = {BACKGROUND: The effects of grazing on soil methane (CH4) uptake in steppe ecosystems are important for understanding carbon sequestration and cycling because the role of grassland soil for CH4 uptake can have major impacts at the global level. Here, a meta-analysis of 27 individual studies was carried out to assess the response patterns of soil CH4 uptake to grazing in steppe ecosystems of China. The weighted log response ratio was used to assess the effect size.

RESULTS: We found that heavy grazing significantly depressed soil CH4 uptake by 36.47%, but light and moderate grazing had no significant effects in grassland ecosystem. The response of grassland soil CH4 uptake to grazing also was found to depend upon grazing intensity, grazing duration and climatic types. The increase in soil temperature and reduced aboveground biomass and soil moisture induced by heavy grazing may be the major regulators of the soil CH4 uptake.

CONCLUSIONS: These findings imply that grazing effects on soil CH4 uptake are highly context-specific and that grazing in different grasslands might be managed differently to help mitigate greenhouse gas emissions.}, } @article {pmid29558930, year = {2018}, author = {Boursereau, R and Abou-Samra, M and Lecompte, S and Noel, L and Brichard, SM}, title = {Downregulation of the NLRP3 inflammasome by adiponectin rescues Duchenne muscular dystrophy.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {33}, pmid = {29558930}, issn = {1741-7007}, abstract = {BACKGROUND: The hormone adiponectin (ApN) exerts powerful anti-inflammatory effects on skeletal muscle and can reverse devastating myopathies, like Duchenne muscular dystrophy (DMD), where inflammation exacerbates disease progression. The NLRP3 inflammasome plays a key role in the inflammation process, and its aberrant activation leads to several inflammatory or immune diseases. Here we investigated the expression of the NLRP inflammasome in skeletal muscle and its contribution to DMD.

RESULTS: We find that NLRP3 is expressed in skeletal muscle and show that ApN downregulates NLRP3 via its anti-inflammatory mediator, miR-711. This repression occurs both in vitro in C2C12 myotubes and in vivo after either local (via muscle electrotransfer) or systemic (by using transgenic mice) ApN supplementation. To explore the role of the NLRP3 inflammasome in a murine model of DMD, we crossed mdx mice with Nlrp3-knockout mice. In mdx mice, all components of the inflammasome were upregulated in muscle, and the complex was overactivated. By contrast, in mdx mice lacking Nlrp3, there was a reduction in caspase-1 activation, inflammation and oxidative stress in dystrophic muscle, and these mice showed higher global muscle force/endurance than regular mdx mice as well as decreased muscle damage. To investigate the relevance of NLPR3 regulation in a human disease context, we characterized NLRP3 expression in primary cultures of myotubes from DMD subjects and found a threefold increase compared to control subjects. This overexpression was attenuated by ApN or miR-711 mimic treatments.

CONCLUSIONS: The NLRP3 inflammasome plays a key pathogenic role in DMD and muscle inflammation, thereby opening new therapeutic perspectives for these and other related disorders.}, } @article {pmid29558904, year = {2018}, author = {El-Keblawy, A and Shabana, HA and Navarro, T and Soliman, S}, title = {Correction to: Effect of maturation time on dormancy and germination of Citrullus colocynthis (Cucurbitaceae) seeds from the Arabian hyper-arid deserts.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {45}, pmid = {29558904}, issn = {1471-2229}, abstract = {Following publication of the original article [1] author Hatem Shabana wrote to say that one of her affiliations was missing. The affiliation is as follows: Departmento de Biología Vegetal, Universidad de Málaga, P. O. Box 59, 29080 Málaga, Spain.}, } @article {pmid29558898, year = {2018}, author = {Li, X and Tao, S and Wei, S and Ming, M and Huang, X and Zhang, S and Wu, J}, title = {The mining and evolutionary investigation of AP2/ERF genes in pear (Pyrus).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {46}, pmid = {29558898}, issn = {1471-2229}, support = {31672111//National Natural Science Foundation of China/ ; CARS-28//China Agriculture Research System/ ; BK20150025//Science Foundation for Distinguished Young Scientists in Jiangsu Province/ ; 2014-NY-025//The Six Talent Peaks Project in Jiangsu Province/ ; }, mesh = {Droughts ; *Evolution, Molecular ; Gene Duplication/genetics ; Gene Expression Regulation, Plant/genetics/physiology ; Plant Proteins/*genetics ; Pyrus/*genetics/physiology ; }, abstract = {BACKGROUND: In plants, ERF genes participate in a variety of regulatory pathways, such as plant growth and biotic and/or abiotic stress responses. Although the genome of Chinese white pear ('Dangshansuli') has been released, knowledge regarding the ERF family in pear, such as gene functions, evolutionary history and expression patterns, remains limited.

RESULTS: In our study, a total of 155 members of ERF families were identified in pear (Pyrus bretschneideri). The Ka and Ks values suggested that whole-genome duplication (WGD) and dispersed duplication have effectively contributed to the expansion of the pear ERF family. Gene structure and phylogeny analysis divided the PbrERF family into 12 groups, and their gene functions were predicted by comparative analysis. qRT-PCR was carried out to verify the relative expression levels of 7 genes in group III using wild and cultivated pear fruits at three key developmental stages. Wild samples had higher expression of these genes than cultivated samples, especially at the enlarged fruit stage. The transcriptome data of pear seedlings subjected to dehydration treatment further revealed that 4 of the 7 genes responded to drought conditions.

CONCLUSION: The AP2/ERF gene family is greatly expanded in pear. Comparative analysis revealed the probability of ERF genes performing functional roles in multiple pathways. Expression analysis at different stages of pear fruit development in wild and cultivated samples indicated that genes in group III might be involved in abiotic and/or biotic stresses. Further transcriptome data on seedlings subjected to drought treatment verified the potential role of ERF genes in stress response. These results will provide a valuable reference for understanding the function and evolution of the ERF family in higher plants.}, } @article {pmid29558897, year = {2018}, author = {Kheravii, SK and Swick, RA and Choct, M and Wu, SB}, title = {Upregulation of genes encoding digestive enzymes and nutrient transporters in the digestive system of broiler chickens by dietary supplementation of fiber and inclusion of coarse particle size corn.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {208}, pmid = {29558897}, issn = {1471-2164}, mesh = {Animal Feed/*analysis ; Animal Nutritional Physiological Phenomena ; Animals ; Biological Transport ; Chickens/*genetics/growth & development ; Diet/*veterinary ; Dietary Fiber/*administration & dosage ; *Dietary Supplements ; Digestive System/enzymology/metabolism ; High-Throughput Nucleotide Sequencing ; Male ; Zea mays/*chemistry ; }, abstract = {BACKGROUND: Measures to improve bird performance have been sought due to the imminent phase out of in-feed antibiotics in poultry and continued demand for higher poultry feeding efficiency. Increasing grain particle size and dietary fibre may improve gizzard function, digestive efficiency and nutrient absorption. This study was conducted to evaluate the effect increased particle size of corn and inclusion of sugarcane bagasse (SB) on mRNA expression of genes encoding digestive enzymes and nutrient transporters in broilers.

RESULTS: A total of 336 day-old Ross 308 males were assigned in a 2 × 2 factorial arrangement of treatments with corn particle size - coarse 3576 μm or fine 1113 μm geometric mean diameter, and SB - 0 or 2% inclusion. Feed conversion ratio (FCR), weight gain and feed intake were measured from d 0-10 and d 10-24. The relative gizzard weight and mRNA expression of genes encoding digestive enzymes and intestinal nutrient transporters were measured on d 24. During d 10-24, a particle size × SB interaction was observed for FCR (P < 0.01), where birds fed coarsely ground corn (CC) with 2% SB had lower FCR than those fed CC without SB. A particle size × SB interaction was observed for both expression of pepsinogen A and C (P < 0.01) which were negatively correlated with FCR on d 24. Addition of 2% SB upregulated pepsinogen A and C only in CC fed birds. Further, 2% SB also upregulated pancreatic amylase (AMY2A) and intestinal cationic amino acid transporter-1 (CAT1). Inclusion of dietary CC upregulated duodenal amino peptidase N (APN), jejunal alanine, serine, cysteine and threonine transporter-1 (ASCT1), and ileal peptide transporter-2 (PepT2).

CONCLUSION: These results suggest that both SB and coarse particle size modulate expression of genes encoding important digestive enzymes and nutrient transporters and thus are directly related to bird performance. These findings provide insights into the combination effects of dietary fiber and particle size in the future management of broiler feeding.}, } @article {pmid29558893, year = {2018}, author = {Koh, H and Livanos, AE and Blaser, MJ and Li, H}, title = {A highly adaptive microbiome-based association test for survival traits.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {210}, pmid = {29558893}, issn = {1471-2164}, support = {R01 DK110014/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01DK090989/DK/NIDDK NIH HHS/United States ; R01DK110014/DK/NIDDK NIH HHS/United States ; U01 AI22285/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Computational Biology/*methods ; *Computer Simulation ; Diabetes Mellitus, Type 1/genetics/microbiology/*mortality ; Feces/microbiology ; *Genetic Markers ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Male ; Mice ; Mice, Inbred NOD ; Microbiota/*genetics ; Phenotype ; Phylogeny ; Prospective Studies ; Survival Rate ; }, abstract = {BACKGROUND: There has been increasing interest in discovering microbial taxa that are associated with human health or disease, gathering momentum through the advances in next-generation sequencing technologies. Investigators have also increasingly employed prospective study designs to survey survival (i.e., time-to-event) outcomes, but current item-by-item statistical methods have limitations due to the unknown true association pattern. Here, we propose a new adaptive microbiome-based association test for survival outcomes, namely, optimal microbiome-based survival analysis (OMiSA). OMiSA approximates to the most powerful association test in two domains: 1) microbiome-based survival analysis using linear and non-linear bases of OTUs (MiSALN) which weighs rare, mid-abundant, and abundant OTUs, respectively, and 2) microbiome regression-based kernel association test for survival traits (MiRKAT-S) which incorporates different distance metrics (e.g., unique fraction (UniFrac) distance and Bray-Curtis dissimilarity), respectively.

RESULTS: We illustrate that OMiSA powerfully discovers microbial taxa whether their underlying associated lineages are rare or abundant and phylogenetically related or not. OMiSA is a semi-parametric method based on a variance-component score test and a re-sampling method; hence, it is free from any distributional assumption on the effect of microbial composition and advantageous to robustly control type I error rates. Our extensive simulations demonstrate the highly robust performance of OMiSA. We also present the use of OMiSA with real data applications.

CONCLUSIONS: OMiSA is attractive in practice as the true association pattern is unpredictable in advance and, for survival outcomes, no adaptive microbiome-based association test is currently available.}, } @article {pmid29558892, year = {2018}, author = {Shashikant, T and Khor, JM and Ettensohn, CA}, title = {Global analysis of primary mesenchyme cell cis-regulatory modules by chromatin accessibility profiling.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {206}, pmid = {29558892}, issn = {1471-2164}, support = {IOS-1354973//National Science Foundation/International ; R24 OD023046-02/CD/ODCDC CDC HHS/United States ; }, mesh = {Animals ; Chromatin/*genetics ; Embryo, Nonmammalian/cytology/*metabolism ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing ; Mesenchymal Stem Cells/cytology/*metabolism ; *Regulatory Sequences, Nucleic Acid ; Strongylocentrotus purpuratus/cytology/*genetics/growth & development ; Transcription Factors/metabolism ; }, abstract = {BACKGROUND: The developmental gene regulatory network (GRN) that underlies skeletogenesis in sea urchins and other echinoderms is a paradigm of GRN structure, function, and evolution. This transcriptional network is deployed selectively in skeleton-forming primary mesenchyme cells (PMCs) of the early embryo. To advance our understanding of this model developmental GRN, we used genome-wide chromatin accessibility profiling to identify and characterize PMC cis-regulatory modules (CRMs).

RESULTS: ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) analysis of purified PMCs provided a global picture of chromatin accessibility in these cells. We used both ATAC-seq and DNase-seq (DNase I hypersensitive site sequencing) to identify > 3000 sites that exhibited increased accessibility in PMCs relative to other embryonic cell lineages, and provide both computational and experimental evidence that a large fraction of these sites represent bona fide skeletogenic CRMs. Putative PMC CRMs were preferentially located near genes differentially expressed by PMCs and consensus binding sites for two key transcription factors in the PMC GRN, Alx1 and Ets1, were enriched in these CRMs. Moreover, a high proportion of candidate CRMs drove reporter gene expression specifically in PMCs in transgenic embryos. Surprisingly, we found that PMC CRMs were partially open in other embryonic lineages and exhibited hyperaccessibility as early as the 128-cell stage.

CONCLUSIONS: Our work provides a comprehensive picture of chromatin accessibility in an early embryonic cell lineage. By identifying thousands of candidate PMC CRMs, we significantly enhance the utility of the sea urchin skeletogenic network as a general model of GRN architecture and evolution. Our work also shows that differential chromatin accessibility, which has been used for the high-throughput identification of enhancers in differentiated cell types, is a powerful approach for the identification of CRMs in early embryonic cells. Lastly, we conclude that in the sea urchin embryo, CRMs that control the cell type-specific expression of effector genes are hyperaccessible several hours in advance of gene activation.}, } @article {pmid29558886, year = {2018}, author = {Ke, F and Gui, JF and Chen, ZY and Li, T and Lei, CK and Wang, ZH and Zhang, QY}, title = {Divergent transcriptomic responses underlying the ranaviruses-amphibian interaction processes on interspecies infection of Chinese giant salamander.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {211}, pmid = {29558886}, issn = {1471-2164}, support = {31430091, 31772890//The National Natural Science Foundation of China/International ; XDA08030202//Strategic Pilot Science and Technology of the Chinese Academy of Sciences Project/International ; 2016FBZ01//Project of State Key Laboratory of Freshwater Ecology and Biotechnology/International ; }, mesh = {Animals ; DNA Virus Infections/*veterinary/virology ; Genome, Viral ; High-Throughput Nucleotide Sequencing ; *Host-Pathogen Interactions ; Ranavirus/*genetics ; *Ranidae/genetics/virology ; Sequence Analysis, DNA/*veterinary ; Thymus Gland/virology ; Transcriptome ; *Urodela/genetics/virology ; Viral Proteins/genetics ; Virus Replication ; }, abstract = {BACKGROUND: Ranaviruses (family Iridoviridae, nucleocytoplasmic large DNA viruses) have been reported as promiscuous pathogens of cold-blooded vertebrates. Rana grylio virus (RGV, a ranavirus), from diseased frog Rana grylio with a genome of 105.79 kb and Andrias davidianus ranavirus (ADRV), from diseased Chinese giant salamander (CGS) with a genome of 106.73 kb, contains 99% homologous genes.

RESULTS: To uncover the differences in virus replication and host responses under interspecies infection, we analyzed transcriptomes of CGS challenged with RGV and ADRV in different time points (1d, 7d) for the first time. A total of 128,533 unigenes were obtained from 820,858,128 clean reads. Transcriptome analysis revealed stronger gene expression of RGV than ADRV at 1 d post infection (dpi), which was supported by infection in vitro. RGV replicated faster and had higher titers than ADRV in cultured CGS cell line. RT-qPCR revealed the RGV genes including the immediate early gene (RGV-89R) had higher expression level than that of ADRV at 1 dpi. It further verified the acute infection of RGV in interspecies infection. The number of differentially expressed genes and enriched pathways from RGV were lower than that from ADRV, which reflected the variant host responses at transcriptional level. No obvious changes of key components in pathway "Antigen processing and presentation" were detected for RGV at 1 dpi. Contrarily, ADRV infection down-regulated the expression levels of MHC I and CD8. The divergent host immune responses revealed the differences between interspecies and natural infection, which may resulted in different fates of the two viruses. Altogether, these results revealed the differences in transcriptome responses among ranavirus interspecies infection of amphibian and new insights in DNA virus-host interactions in interspecies infection.

CONCLUSION: The DNA virus (RGV) not only expressed self-genes and replicated quickly after entry into host under interspecies infection, but also avoided the over-activation of host responses. The strategy could gain time for the survival of interspecies pathogen, and may provide opportunity for its adaptive evolution and interspecies transmission.}, } @article {pmid29558883, year = {2018}, author = {Liu, J and Wang, G and Lin, Q and Liang, W and Gao, Z and Mu, P and Li, G and Song, L}, title = {Systematic analysis of the lysine malonylome in common wheat.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {209}, pmid = {29558883}, issn = {1471-2164}, support = {2016lzgc023//the agricultural well-breed project in Shandong Province/International ; 2014GJJS0201//the Major Key Technology Project for Independent Innovation in Shandong Province/International ; SDAIT-04-021-09//the Innovation Team of Wheat for Modern Agricultural Technology System in Shandong Province/International ; 31601624//the National Natural Science Foundation of China/International ; tshw20130963//the Taishan Scholar Construction Foundation of Shandong Province/International ; }, mesh = {Computational Biology ; Lysine/*metabolism ; Malonates/*metabolism ; Plant Proteins/*metabolism ; *Protein Processing, Post-Translational ; Proteome/*analysis ; Proteomics/methods ; Triticum/*metabolism ; }, abstract = {BACKGROUND: Protein lysine malonylation, a newly discovered post-translational modification (PTM), plays an important role in diverse metabolic processes in both eukaryotes and prokaryotes. Common wheat is a major global cereal crop. However, the functions of lysine malonylation are relatively unknown in this crop. Here, a global analysis of lysine malonylation was performed in wheat.

RESULTS: In total, 342 lysine malonylated sites were identified in 233 proteins. Bioinformatics analysis showed that the frequency of arginine (R) in position + 1 was highest, and a modification motif, KmaR, was identified. The malonylated proteins were located in multiple subcellular compartments, especially in the cytosol (45%) and chloroplast (30%). The identified proteins were found to be involved in diverse pathways, such as carbon metabolism, the Calvin cycle, and the biosynthesis of amino acids, suggesting an important role for lysine malonylation in these processes. Protein interaction network analysis revealed eight highly interconnected clusters of malonylated proteins, and 137 malonylated proteins were mapped to the protein network database. Moreover, five proteins were simultaneously modified by lysine malonylation, acetylation and succinylation, suggesting that these three PTMs may coordinately regulate the function of many proteins in common wheat.

CONCLUSIONS: Our results suggest that lysine malonylation is involved in a variety of biological processes, especially carbon fixation in photosynthetic organisms. These data represent the first report of the lysine malonylome in common wheat and provide an important dataset for further exploring the physiological role of lysine malonylation in wheat and likely all plants.}, } @article {pmid29558828, year = {2018}, author = {Apostolou, M and Wang, Y}, title = {Parent-Offspring Conflict Over Mating in Chinese Families: Comparisons With Greek Cypriot Families.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704918764162}, doi = {10.1177/1474704918764162}, pmid = {29558828}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; China ; Choice Behavior/physiology ; Cross-Cultural Comparison ; Cyprus ; Family Conflict/*psychology ; Female ; Humans ; Male ; Marriage/*psychology ; Middle Aged ; Parent-Child Relations ; Parents/*psychology ; Prospective Studies ; Young Adult ; }, abstract = {Parents and their children are genetically related but not genetically identical, a fact that leads to conflict between the two. One such domain of conflict is mate choice, where in-law and mate preferences diverge. The current research examined this divergence in preferences in the Chinese culture and how it varied across cultural contexts. More specifically, we have employed an online sample of 356 Chinese families, and we asked parents to rate the importance of several traits in a prospective spouse for their children and their children to rate the importance of the same traits in a prospective spouse for themselves. Comparisons of parents' and children's answers indicated a disagreement in several domains including good looks and family oriented. It was also found that there was more disagreement between parents and sons than between parents and daughters. Finally, the responses of Chinese parents and their children in the current study were compared with the responses of Greek Cypriot parents and their children from a previous study. It was found that, across several domains, there was more disagreement between parents and sons in the Chinese sample, while for the family oriented and the chastity, there was more parents-sons and parents-daughters disagreement in the Chinese sample. The implications of these findings were further examined.}, } @article {pmid29558827, year = {2018}, author = {Borráz-León, JI and Cerda-Molina, AL and Rantala, MJ and Mayagoitia-Novales, L}, title = {Choosing Fighting Competitors Among Men: Testosterone, Personality, and Motivations.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704918757243}, doi = {10.1177/1474704918757243}, pmid = {29558827}, issn = {1474-7049}, mesh = {Adult ; Aggression/psychology ; Choice Behavior/physiology ; Competitive Behavior/*physiology ; Humans ; Male ; *Masculinity ; Motivation/*physiology ; Personality/*physiology ; Saliva/chemistry ; *Self Concept ; Testosterone/*analysis ; Young Adult ; }, abstract = {Higher testosterone levels have been positively related to a variety of social behaviors and personality traits associated with intrasexual competition. The aim of this study was to evaluate the role of testosterone levels and personality traits such as aggressiveness, competitiveness, and self-esteem on the task of choosing a fighting competitor (a rival) with or without a motivation to fight. In Study 1, a group of 119 men participated in a task for choosing a rival through pictures of men with high-dominant masculinity versus low-dominant masculinity. Participants completed three personality questionnaires and donated two saliva samples (pre-test and post-test sample) to quantify their testosterone levels. We found that the probability of choosing high-dominant masculine men as rivals increased with higher aggressiveness scores. In Study 2, the task of choosing rivals was accompanied by motivations to fight (pictures of women with high or low waist-to-hip ratio [WHR]). In this context, we observed that the probability of choosing dominant masculine men as rivals depended on the WHR of the women. Overall, average levels of post-test testosterone, aggressiveness, and high self-esteem increased the probability to fight for women with low WHR independently of the dominance masculinity of the rivals. Our results indicate that human decisions, in the context of intrasexual competition and mate choice, are regulated by physiological and psychological mechanisms allowing men to increase their biological fitness. We discuss our results in the light of the plasticity of human behavior according to biological and environmental forces.}, } @article {pmid29557775, year = {2018}, author = {Schroeder, BK and Schneider, WL and Luster, DG and Sechler, A and Murray, TD}, title = {Rathayibacter agropyri (non O'Gara 1916) comb. nov., nom. rev., isolated from western wheatgrass (Pascopyrum smithii).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1519-1525}, doi = {10.1099/ijsem.0.002708}, pmid = {29557775}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Montana ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; *Phylogeny ; Poaceae/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; Washington ; }, abstract = {Aplanobacter agropyri was first described in 1915 by O'Gara and later transferred to the genus Corynebacterium by Burkholder in 1948 but it was not included in the Approved Lists of Bacterial Names in 1980 and, consequently, is not recognized as a validly published species. In the 1980s, bacteria resembling Corynebacterium agropyri were isolated from plant samples stored at the Washington State Mycological Herbarium and from a diseased wheatgrass plant collected in Cardwell, Montana, USA. In the framework of this study, eight additional isolates were recovered from the same herbarium plant samples in 2011. The isolates are slow-growing, yellow-pigmented, Gram-stain-positive and coryneform. The peptidoglycan is type B2γ containing diaminobutyric acid, alanine, glycine and glutamic acid, the cell-wall sugars are rhamnose and mannose, the major respiratory quinone is MK-10, and the major fatty acids are anteiso-15 : 0, anteiso 17 : 0 and iso-16 : 0, all of which are typical of the genus Rathayibacter. Phylogenetic analysis of 16S rRNA gene sequences placed the strains in the genus Rathayibacter and distinguished them from the six other described species of Rathayibacter. DNA-DNA hybridization confirmed that the strains were members of a novel species. Based on phenotypic, chemotaxonomic and phylogenetic characterization, it appears that strains CA-1 to CA-12 represent a novel species, and the name Rathayibacter agropyri (non O'Gara 1916) comb. nov., nom. rev. is proposed; the type strain is CA-4T (=DSM 104101T;=ATCC TSD-78T).}, } @article {pmid29557772, year = {2018}, author = {Wei, Y and Fang, J and Xu, Y and Zhao, W and Cao, J}, title = {Corynebacterium hadale sp. nov. isolated from hadopelagic water of the New Britain Trench.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1474-1478}, doi = {10.1099/ijsem.0.002695}, pmid = {29557772}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; Corynebacterium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Pacific Ocean ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel heterotrophic, Gram-stain-positive, facultatively anaerobic and rod-shaped bacterium, designated strain NBT06-6T, was isolated from the deep seawater in the New Britain Trench and characterized phylogenetically and phenotypically. Optimal bacterial growth occurred at 35 °C (range 22-41 °C), at pH 6 (4-8) and with 4 % (w/v) NaCl (0-10 %). The strain grew at hydrostatic pressures of 0.1-100 MPa (optimum, 0.1 MPa) at 35 °C. Phylogenetic analysis of the 16S rRNA gene sequences indicated that strain NBT06-6T belonged to the genus Corynebacterium, with the highest sequence similarity (97.9 %) to Corynebacterium imitans, and shared low 16S rRNA gene sequence similarities (<97.0 %) with other type strains. The major respiratory menaquinones were MK-8(H2) and MK-9(H2). The polar lipids were diphosphatidyglycerol, phosphatidylglycerol, phosphatidylinositol, three unidentified aminoglycolipids and four unidentified glycolipids. The major fatty acids detected were C18 : 1ω9c, C16 : 0 and C15 : 0. Strain NBT06-6T contained meso-diaminopimelic acid and mycolic acids in its cell wall, and mannose, galactose, glucose, arabinose and ribose as major whole-cell sugars. The G+C content of the genomic DNA was 65.1 mol%. The digital DNA-DNA hybridization value and the average nucleotide identity between strain NBT06-6T and C. imitans were 24.5±2.4 and 81.9 %, respectively. The combined genotypic and phenotypic data indicated that strain NBT06-6T represents a novel species of the genus Corynebacterium, for which the name Corynebacterium hadale sp. nov. is proposed, with the type strain NBT06-6T (=MCCC 1K03347T=DSM 105365T).}, } @article {pmid29557768, year = {2018}, author = {Sakurai, K and Kawasaki, H}, title = {Genetic variation during long-term preservation of bacteria in public culture collections.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1815-1821}, doi = {10.1099/ijsem.0.002717}, pmid = {29557768}, issn = {1466-5034}, mesh = {Bacteria/*genetics ; Bacterial Typing Techniques ; *Biological Specimen Banks ; DNA, Bacterial/genetics ; Exons ; Introns ; Phenotype ; *Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; }, abstract = {Phenotypic and genetic changes during long-term preservation have been observed in microbial strains at culture collections (CCs). It is imperative to verify the effects of these changes on quality of the strains preserved at CCs. In this study, we performed genome-wide single-nucleotide polymorphism (SNP) analysis of different production lots, which had been derived from the same origin and preserved at the NITE Biological Resource Center (NBRC) for a 4-38-year period by the vacuum liquid drying method at 4 °C. The analysis was conducted for three sets of lots derived from Cellulomonas fimi NBRC 15513T, Corynebacterium glutamicum NBRC 12168T, and Saccharomonospora viridis NBRC 12207T. SNPs were found in all sets studied for comparison purposes. In sets of two or three lots, genomic SNPs were found in both non-coding sequences (non-CDSs) and in coding sequences (CDSs), and the SNPs in the CDSs resulted in non-synonymous mutations. These data indicated that genomic variation occurred during long-term preservation.}, } @article {pmid29557767, year = {2018}, author = {López, G and Díaz-Cárdenas, C and David Alzate, J and Gonzalez, LN and Shapiro, N and Woyke, T and Kyrpides, NC and Restrepo, S and Baena, S}, title = {Description of Alicyclobacillus montanus sp. nov., a mixotrophic bacterium isolated from acidic hot springs.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1608-1615}, doi = {10.1099/ijsem.0.002718}, pmid = {29557767}, issn = {1466-5034}, mesh = {Alicyclobacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Colombia ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hot Springs/*microbiology ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Three morphologically similar thermo-acidophilic strains, USBA-GBX-501, USBA-GBX-502 and USBA-GBX-503T, were isolated from acidic thermal springs at the National Natural Park Los Nevados (Colombia). All isolates were spore-forming, Gram-stain-positive and motile, growing aerobically at 25-55 °C (optimum ~45 °C) and at pH 1.5-4.5 (optimum pH ~3.0). Phylogenetic analysis of the 16S rRNA gene sequences of these isolates showed an almost identical sequence (99.0 % similarity) and they formed a robust cluster with the closest relative Alicyclobacillus tolerans DSM 16297T with a sequence similarity of 99.0 %. Average similarity to other species of the genus Alicyclobacillus was 93.0 % and average similarity to species of the genus Effusibacillus was 90 %. In addition, the level of DNA-DNA hybridization between strain USBA-GBX-503T and Alicyclobacillus tolerans DSM 16297T was 31.7 %. The genomic DNA G+C content of strain USBA-GBX-503T was 44.6 mol%. The only menaquinone was MK-7 (100.0 %). No ω-alicyclic fatty acids were detected in strain USBA-GBX-503T, and the major cellular fatty acids were C18 : 1ω7c, anteiso-C17 : 0 and iso-C17 : 0. Based on phenotypic and chemotaxonomic characteristics, phylogenetic analysis and DNA-DNA relatedness values, along with low levels of identity at the whole genome level (ANIb and ANIm values of <67.0 and <91.0 %, respectively), it can be concluded that strain USBA-GBX-503T represents a novel species of the genus Alicyclobacillus, for which the name Alicyclobacillus montanus sp. nov. is proposed. The type strain is USBA-GBX-503T (=CMPUJ UGB U503T=CBMAI1927T).}, } @article {pmid29556741, year = {2018}, author = {Viljoen, E and Odeny, DA and Coetzee, MPA and Berger, DK and Rees, DJG}, title = {Application of Chloroplast Phylogenomics to Resolve Species Relationships Within the Plant Genus Amaranthus.}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {216-239}, pmid = {29556741}, issn = {1432-1432}, abstract = {Amaranthus species are an emerging and promising nutritious traditional vegetable food source. Morphological plasticity and poorly resolved dendrograms have led to the need for well resolved species phylogenies. We hypothesized that whole chloroplast phylogenomics would result in more reliable differentiation between closely related amaranth species. The aims of the study were therefore: to construct a fully assembled, annotated chloroplast genome sequence of Amaranthus tricolor; to characterize Amaranthus accessions phylogenetically by comparing barcoding genes (matK, rbcL, ITS) with whole chloroplast sequencing; and to use whole chloroplast phylogenomics to resolve deeper phylogenetic relationships. We generated a complete A. tricolor chloroplast sequence of 150,027 bp. The three barcoding genes revealed poor inter- and intra-species resolution with low bootstrap support. Whole chloroplast phylogenomics of 59 Amaranthus accessions increased the number of parsimoniously informative sites from 92 to 481 compared to the barcoding genes, allowing improved separation of amaranth species. Our results support previous findings that two geographically independent domestication events of Amaranthus hybridus likely gave rise to several species within the Hybridus complex, namely Amaranthus dubius, Amaranthus quitensis, Amaranthus caudatus, Amaranthus cruentus and Amaranthus hypochondriacus. Poor resolution of species within the Hybridus complex supports the recent and ongoing domestication within the complex, and highlights the limitation of chloroplast data for resolving recent evolution. The weedy Amaranthus retroflexus and Amaranthus powellii was found to share a common ancestor with the Hybridus complex. Leafy amaranth, Amaranthus tricolor, Amaranthus blitum, Amaranthus viridis and Amaranthus graecizans formed a stable sister lineage to the aforementioned species across the phylogenetic trees. This study demonstrates the power of next-generation sequencing data and reference-based assemblies to resolve phylogenies, and also facilitated the identification of unknown Amaranthus accessions from a local genebank. The informative phylogeny of the Amaranthus genus will aid in selecting accessions for breeding advanced genotypes to satisfy global food demand.}, } @article {pmid29556740, year = {2018}, author = {Paquola, ACM and Asif, H and Pereira, CAB and Feltes, BC and Bonatto, D and Lima, WC and Menck, CFM}, title = {Horizontal Gene Transfer Building Prokaryote Genomes: Genes Related to Exchange Between Cell and Environment are Frequently Transferred.}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {190-203}, pmid = {29556740}, issn = {1432-1432}, abstract = {Horizontal gene transfer (HGT) has a major impact on the evolution of prokaryotic genomes, as it allows genes evolved in different contexts to be combined in a single genome, greatly enhancing the ways evolving organisms can explore the gene content space and adapt to the environment. A systematic analysis of HGT in a large number of genomes is of key importance in understanding the impact of HGT in the evolution of prokaryotes. We developed a method for the detection of genes that potentially originated by HGT based on the comparison of BLAST scores between homologous genes to 16S rRNA-based phylogenetic distances between the involved organisms. The approach was applied to 697 prokaryote genomes and estimated that in average approximately 15% of the genes in prokaryote genomes originated by HGT, with a clear correlation between the proportion of predicted HGT genes and the size of the genome. The methodology was strongly supported by evolutionary relationships, as tested by the direct phylogenetic reconstruction of many of the HGT candidates. Studies performed with Escherichia coli W3110 genome clearly show that HGT proteins have fewer interactions when compared to those predicted as vertical inherited, an indication that the number of protein partners imposes limitations to horizontal transfer. A detailed functional classification confirms that genes related to protein translation are vertically inherited, whereas interestingly, transport and binding proteins are strongly enriched among HGT genes. Because these genes are related to the cell exchange with their environment, their transfer most likely contributed to successful adaptation throughout evolution.}, } @article {pmid29556711, year = {2018}, author = {Hou, L and Wu, Q and Gu, Q and Zhou, Q and Zhang, J}, title = {Community Structure Analysis and Biodegradation Potential of Aniline-Degrading Bacteria in Biofilters.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {918-924}, pmid = {29556711}, issn = {1432-0991}, support = {2014A040401053//the Science and Technology Planning Project of Guangdong Province/ ; 2016A040403086//the Science and Technology Planning Project of Guangdong Province/ ; }, mesh = {Aniline Compounds/*metabolism ; Bacteria/classification/genetics/*isolation & purification/*metabolism ; Biodegradation, Environmental ; Biodiversity ; DNA, Bacterial/genetics ; Drinking Water/chemistry/*microbiology ; RNA, Ribosomal, 16S/genetics ; Water Pollutants, Chemical/chemistry/*metabolism ; Water Purification/*instrumentation ; }, abstract = {Aniline has aroused general concern owing to its strong toxicity and widespread distribution in water and soil. In the present study, the bacterial community composition before and after aniline acclimation was investigated. High-throughput Illumina MiSeq sequencing analysis illustrated a large shift in the structure of the bacterial community during the aniline acclimation period. Bacillus, Lactococcus, and Enterococcus were the dominant bacteria in biologically activated carbon before acclimation. However, the proportions of Pseudomonas, Thermomonas, and Acinetobacter increased significantly and several new bacterial taxa appeared after aniline acclimation, indicating that aniline acclimation had a strong impact on the bacterial community structure of biological activated carbon samples. Strain AN-1 accounted for the highest number of colonies on incubation plates and was identified as Acinetobacter sp. according to phylogenetic analysis of the 16S ribosomal ribonucleic acid gene sequence. Strain AN-1 was able to grow on aniline at pH value 4.0-10.0 and showed high aniline-degrading ability at neutral pH.}, } @article {pmid29556109, year = {2018}, author = {Zhalnina, K and Louie, KB and Hao, Z and Mansoori, N and da Rocha, UN and Shi, S and Cho, H and Karaoz, U and Loqué, D and Bowen, BP and Firestone, MK and Northen, TR and Brodie, EL}, title = {Dynamic root exudate chemistry and microbial substrate preferences drive patterns in rhizosphere microbial community assembly.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {470-480}, doi = {10.1038/s41564-018-0129-3}, pmid = {29556109}, issn = {2058-5276}, abstract = {Like all higher organisms, plants have evolved in the context of a microbial world, shaping both their evolution and their contemporary ecology. Interactions between plant roots and soil microorganisms are critical for plant fitness in natural environments. Given this co-evolution and the pivotal importance of plant-microbial interactions, it has been hypothesized, and a growing body of literature suggests, that plants may regulate the composition of their rhizosphere to promote the growth of microorganisms that improve plant fitness in a given ecosystem. Here, using a combination of comparative genomics and exometabolomics, we show that pre-programmed developmental processes in plants (Avena barbata) result in consistent patterns in the chemical composition of root exudates. This chemical succession in the rhizosphere interacts with microbial metabolite substrate preferences that are predictable from genome sequences. Specifically, we observed a preference by rhizosphere bacteria for consumption of aromatic organic acids exuded by plants (nicotinic, shikimic, salicylic, cinnamic and indole-3-acetic). The combination of these plant exudation traits and microbial substrate uptake traits interact to yield the patterns of microbial community assembly observed in the rhizosphere of an annual grass. This discovery provides a mechanistic underpinning for the process of rhizosphere microbial community assembly and provides an attractive direction for the manipulation of the rhizosphere microbiome for beneficial outcomes.}, } @article {pmid29556108, year = {2018}, author = {Serafim, TD and Coutinho-Abreu, IV and Oliveira, F and Meneses, C and Kamhawi, S and Valenzuela, JG}, title = {Sequential blood meals promote Leishmania replication and reverse metacyclogenesis augmenting vector infectivity.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {548-555}, pmid = {29556108}, issn = {2058-5276}, support = {Z01 AI000932-06/NULL/Intramural NIH HHS/United States ; }, abstract = {Sand flies, similar to most vectors, take multiple blood meals during their lifetime1-4. The effect of subsequent blood meals on pathogens developing in the vector and their impact on disease transmission have never been examined. Here, we show that ingestion of a second uninfected blood meal by Leishmania-infected sand flies triggers dedifferentiation of metacyclic promastigotes, considered a terminally differentiated stage inside the vector 5 , to a leptomonad-like stage, the retroleptomonad promastigote. Reverse metacyclogenesis occurs after every subsequent blood meal where retroleptomonad promastigotes rapidly multiply and differentiate to metacyclic promastigotes enhancing sand fly infectiousness. Importantly, a subsequent blood meal amplifies the few Leishmania parasites acquired by feeding on infected hosts by 125-fold, and increases lesion frequency by fourfold, in twice-fed compared with single-fed flies. These findings place readily available blood sources as a critical element in transmission and propagation of vector-borne pathogens.}, } @article {pmid29556107, year = {2018}, author = {Tramontano, M and Andrejev, S and Pruteanu, M and Klünemann, M and Kuhn, M and Galardini, M and Jouhten, P and Zelezniak, A and Zeller, G and Bork, P and Typas, A and Patil, KR}, title = {Nutritional preferences of human gut bacteria reveal their metabolic idiosyncrasies.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {514-522}, doi = {10.1038/s41564-018-0123-9}, pmid = {29556107}, issn = {2058-5276}, abstract = {Bacterial metabolism plays a fundamental role in gut microbiota ecology and host-microbiome interactions. Yet the metabolic capabilities of most gut bacteria have remained unknown. Here we report growth characteristics of 96 phylogenetically diverse gut bacterial strains across 4 rich and 15 defined media. The vast majority of strains (76) grow in at least one defined medium, enabling accurate assessment of their biosynthetic capabilities. These do not necessarily match phylogenetic similarity, thus indicating a complex evolution of nutritional preferences. We identify mucin utilizers and species inhibited by amino acids and short-chain fatty acids. Our analysis also uncovers media for in vitro studies wherein growth capacity correlates well with in vivo abundance. Further value of the underlying resource is demonstrated by correcting pathway gaps in available genome-scale metabolic models of gut microorganisms. Together, the media resource and the extracted knowledge on growth abilities widen experimental and computational access to the gut microbiota.}, } @article {pmid29556092, year = {2018}, author = {Vihervaara, A and Duarte, FM and Lis, JT}, title = {Molecular mechanisms driving transcriptional stress responses.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {6}, pages = {385-397}, pmid = {29556092}, issn = {1471-0064}, support = {R01 GM025232/GM/NIGMS NIH HHS/United States ; }, abstract = {Proteotoxic stress, that is, stress caused by protein misfolding and aggregation, triggers the rapid and global reprogramming of transcription at genes and enhancers. Genome-wide assays that track transcriptionally engaged RNA polymerase II (Pol II) at nucleotide resolution have provided key insights into the underlying molecular mechanisms that regulate transcriptional responses to stress. In addition, recent kinetic analyses of transcriptional control under heat stress have shown how cells 'prewire' and rapidly execute genome-wide changes in transcription while concurrently becoming poised for recovery. The regulation of Pol II at genes and enhancers in response to heat stress is coupled to chromatin modification and compartmentalization, as well as to co-transcriptional RNA processing. These mechanistic features seem to apply broadly to other coordinated genome-regulatory responses.}, } @article {pmid29556080, year = {2018}, author = {Barnes, MD and Glew, L and Wyborn, C and Craigie, ID}, title = {Prevent perverse outcomes from global protected area policy.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {759-762}, doi = {10.1038/s41559-018-0501-y}, pmid = {29556080}, issn = {2397-334X}, } @article {pmid29556079, year = {2018}, author = {Sswat, M and Stiasny, MH and Taucher, J and Algueró-Muñiz, M and Bach, LT and Jutfelt, F and Riebesell, U and Clemmesen, C}, title = {Food web changes under ocean acidification promote herring larvae survival.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {836-840}, doi = {10.1038/s41559-018-0514-6}, pmid = {29556079}, issn = {2397-334X}, abstract = {Ocean acidification-the decrease in seawater pH due to rising CO2 concentrations-has been shown to lower survival in early life stages of fish and, as a consequence, the recruitment of populations including commercially important species. To date, ocean-acidification studies with fish larvae have focused on the direct physiological impacts of elevated CO2, but largely ignored the potential effects of ocean acidification on food web interactions. In an in situ mesocosm study on Atlantic herring (Clupea harengus) larvae as top predators in a pelagic food web, we account for indirect CO2 effects on larval survival mediated by changes in food availability. The community was exposed to projected end-of-the-century CO2 conditions (~760 µatm pCO2) over a period of 113 days. In contrast with laboratory studies that reported a decrease in fish survival, the survival of the herring larvae in situ was significantly enhanced by 19 ± 2%. Analysis of the plankton community dynamics suggested that the herring larvae benefitted from a CO2-stimulated increase in primary production. Such indirect effects may counteract the possible direct negative effects of ocean acidification on the survival of fish early life stages. These findings emphasize the need to assess the food web effects of ocean acidification on fish larvae before we can predict even the sign of change in fish recruitment in a high-CO2 ocean.}, } @article {pmid29556078, year = {2018}, author = {Ruiz-Orera, J and Verdaguer-Grau, P and Villanueva-Cañas, JL and Messeguer, X and Albà, MM}, title = {Translation of neutrally evolving peptides provides a basis for de novo gene evolution.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {890-896}, doi = {10.1038/s41559-018-0506-6}, pmid = {29556078}, issn = {2397-334X}, abstract = {Accumulating evidence indicates that some protein-coding genes have originated de novo from previously non-coding genomic sequences. However, the processes underlying de novo gene birth are still enigmatic. In particular, the appearance of a new functional protein seems highly improbable unless there is already a pool of neutrally evolving peptides that are translated at significant levels and that can at some point acquire new functions. Here, we use deep ribosome-profiling sequencing data, together with proteomics and single nucleotide polymorphism information, to search for these peptides. We find hundreds of open reading frames that are translated and that show no evolutionary conservation or selective constraints. These data suggest that the translation of these neutrally evolving peptides may be facilitated by the chance occurrence of open reading frames with a favourable codon composition. We conclude that the pervasive translation of the transcriptome provides plenty of material for the evolution of new functional proteins.}, } @article {pmid29556077, year = {2018}, author = {Letelier, J and de la Calle-Mustienes, E and Pieretti, J and Naranjo, S and Maeso, I and Nakamura, T and Pascual-Anaya, J and Shubin, NH and Schneider, I and Martinez-Morales, JR and Gómez-Skarmeta, JL}, title = {A conserved Shh cis-regulatory module highlights a common developmental origin of unpaired and paired fins.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {504-509}, pmid = {29556077}, issn = {1546-1718}, support = {740041//European Research Council/International ; }, abstract = {Despite their evolutionary, developmental and functional importance, the origin of vertebrate paired appendages remains uncertain. In mice, a single enhancer termed ZRS is solely responsible for Shh expression in limbs. Here, zebrafish and mouse transgenic assays trace the functional equivalence of ZRS across the gnathostome phylogeny. CRISPR/Cas9-mediated deletion of the medaka (Oryzias latipes) ZRS and enhancer assays identify the existence of ZRS shadow enhancers in both teleost and human genomes. Deletion of both ZRS and shadow ZRS abolishes shh expression and completely truncates pectoral fin formation. Strikingly, deletion of ZRS results in an almost complete ablation of the dorsal fin. This finding indicates that a ZRS-Shh regulatory module is shared by paired and median fins and that paired fins likely emerged by the co-option of developmental programs established in the median fins of stem gnathostomes. Shh function was later reinforced in pectoral fin development with the recruitment of shadow enhancers, conferring additional robustness.}, } @article {pmid29556036, year = {2018}, author = {Choi, Y and Bowman, JW and Jung, JU}, title = {Autophagy during viral infection - a double-edged sword.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {6}, pages = {341-354}, doi = {10.1038/s41579-018-0003-6}, pmid = {29556036}, issn = {1740-1534}, abstract = {Autophagy is a powerful tool that host cells use to defend against viral infection. Double-membrane vesicles, termed autophagosomes, deliver trapped viral cargo to the lysosome for degradation. Specifically, autophagy initiates an innate immune response by cooperating with pattern recognition receptor signalling to induce interferon production. It also selectively degrades immune components associated with viral particles. Following degradation, autophagy coordinates adaptive immunity by delivering virus-derived antigens for presentation to T lymphocytes. However, in an ongoing evolutionary arms race, viruses have acquired the potent ability to hijack and subvert autophagy for their benefit. In this Review, we focus on the key regulatory steps during viral infection in which autophagy is involved and discuss the specific molecular mechanisms that diverse viruses use to repurpose autophagy for their life cycle and pathogenesis.}, } @article {pmid29555994, year = {2018}, author = {Maier, L and Pruteanu, M and Kuhn, M and Zeller, G and Telzerow, A and Anderson, EE and Brochado, AR and Fernandez, KC and Dose, H and Mori, H and Patil, KR and Bork, P and Typas, A}, title = {Extensive impact of non-antibiotic drugs on human gut bacteria.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {623-628}, pmid = {29555994}, issn = {1476-4687}, support = {669830//European Research Council/International ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Antipsychotic Agents/pharmacology ; Bacteria/classification/*drug effects/growth & development ; Cohort Studies ; *Drug Evaluation, Preclinical ; Drug Resistance, Bacterial/*drug effects ; Gastrointestinal Microbiome/*drug effects ; High-Throughput Screening Assays ; Humans ; In Vitro Techniques ; Microbial Viability/drug effects ; Reproducibility of Results ; Symbiosis/drug effects ; }, abstract = {A few commonly used non-antibiotic drugs have recently been associated with changes in gut microbiome composition, but the extent of this phenomenon is unknown. Here, we screened more than 1,000 marketed drugs against 40 representative gut bacterial strains, and found that 24% of the drugs with human targets, including members of all therapeutic classes, inhibited the growth of at least one strain in vitro. Particular classes, such as the chemically diverse antipsychotics, were overrepresented in this group. The effects of human-targeted drugs on gut bacteria are reflected on their antibiotic-like side effects in humans and are concordant with existing human cohort studies. Susceptibility to antibiotics and human-targeted drugs correlates across bacterial species, suggesting common resistance mechanisms, which we verified for some drugs. The potential risk of non-antibiotics promoting antibiotic resistance warrants further exploration. Our results provide a resource for future research on drug-microbiome interactions, opening new paths for side effect control and drug repurposing, and broadening our view of antibiotic resistance.}, } @article {pmid29555993, year = {2018}, author = {Citron, RI and Manga, M and Hemingway, DJ}, title = {Timing of oceans on Mars from shoreline deformation.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {643-646}, pmid = {29555993}, issn = {1476-4687}, abstract = {Widespread evidence points to the existence of an ancient Martian ocean. Most compelling are the putative ancient shorelines in the northern plains. However, these shorelines fail to follow an equipotential surface, and this has been used to challenge the notion that they formed via an early ocean and hence to question the existence of such an ocean. The shorelines' deviation from a constant elevation can be explained by true polar wander occurring after the formation of Tharsis, a volcanic province that dominates the gravity and topography of Mars. However, surface loading from the oceans can drive polar wander only if Tharsis formed far from the equator, and most evidence indicates that Tharsis formed near the equator, meaning that there is no current explanation for the shorelines' deviation from an equipotential that is consistent with our geophysical understanding of Mars. Here we show that variations in shoreline topography can be explained by deformation caused by the emplacement of Tharsis. We find that the shorelines must have formed before and during the emplacement of Tharsis, instead of afterwards, as previously assumed. Our results imply that oceans on Mars formed early, concurrent with the valley networks, and point to a close relationship between the evolution of oceans on Mars and the initiation and decline of Tharsis volcanism, with broad implications for the geology, hydrological cycle and climate of early Mars.}, } @article {pmid29555992, year = {2018}, author = {Ye, L and Kang, M and Liu, J and von Cube, F and Wicker, CR and Suzuki, T and Jozwiak, C and Bostwick, A and Rotenberg, E and Bell, DC and Fu, L and Comin, R and Checkelsky, JG}, title = {Massive Dirac fermions in a ferromagnetic kagome metal.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {638-642}, pmid = {29555992}, issn = {1476-4687}, abstract = {The kagome lattice is a two-dimensional network of corner-sharing triangles that is known to host exotic quantum magnetic states. Theoretical work has predicted that kagome lattices may also host Dirac electronic states that could lead to topological and Chern insulating phases, but these states have so far not been detected in experiments. Here we study the d-electron kagome metal Fe3Sn2, which is designed to support bulk massive Dirac fermions in the presence of ferromagnetic order. We observe a temperature-independent intrinsic anomalous Hall conductivity that persists above room temperature, which is suggestive of prominent Berry curvature from the time-reversal-symmetry-breaking electronic bands of the kagome plane. Using angle-resolved photoemission spectroscopy, we observe a pair of quasi-two-dimensional Dirac cones near the Fermi level with a mass gap of 30 millielectronvolts, which correspond to massive Dirac fermions that generate Berry-curvature-induced Hall conductivity. We show that this behaviour is a consequence of the underlying symmetry properties of the bilayer kagome lattice in the ferromagnetic state and the atomic spin-orbit coupling. This work provides evidence for a ferromagnetic kagome metal and an example of emergent topological electronic properties in a correlated electron system. Our results provide insight into the recent discoveries of exotic electronic behaviour in kagome-lattice antiferromagnets and may enable lattice-model realizations of fractional topological quantum states.}, } @article {pmid29555780, year = {2018}, author = {Benitez-Quiroz, CF and Srinivasan, R and Martinez, AM}, title = {Facial color is an efficient mechanism to visually transmit emotion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3581-3586}, pmid = {29555780}, issn = {1091-6490}, support = {R01 DC014498/DC/NIDCD NIH HHS/United States ; }, mesh = {Adult ; *Color ; Emotions/*physiology ; Face/*physiology ; *Facial Expression ; Facial Muscles/*physiology ; Female ; Humans ; Male ; *Pattern Recognition, Visual ; Young Adult ; }, abstract = {Facial expressions of emotion in humans are believed to be produced by contracting one's facial muscles, generally called action units. However, the surface of the face is also innervated with a large network of blood vessels. Blood flow variations in these vessels yield visible color changes on the face. Here, we study the hypothesis that these visible facial colors allow observers to successfully transmit and visually interpret emotion even in the absence of facial muscle activation. To study this hypothesis, we address the following two questions. Are observable facial colors consistent within and differential between emotion categories and positive vs. negative valence? And does the human visual system use these facial colors to decode emotion from faces? These questions suggest the existence of an important, unexplored mechanism of the production of facial expressions of emotion by a sender and their visual interpretation by an observer. The results of our studies provide evidence in favor of our hypothesis. We show that people successfully decode emotion using these color features, even in the absence of any facial muscle activation. We also demonstrate that this color signal is independent from that provided by facial muscle movements. These results support a revised model of the production and perception of facial expressions of emotion where facial color is an effective mechanism to visually transmit and decode emotion.}, } @article {pmid29555779, year = {2018}, author = {Jin, X and Riedel-Kruse, IH}, title = {Biofilm Lithography enables high-resolution cell patterning via optogenetic adhesin expression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3698-3703}, pmid = {29555779}, issn = {1091-6490}, mesh = {Adhesins, Escherichia coli/genetics/*metabolism/radiation effects ; Bacterial Adhesion/*physiology/radiation effects ; Biofilms/*growth & development/radiation effects ; Escherichia coli/*growth & development/radiation effects ; *Light ; Optogenetics/*methods ; }, abstract = {Bacterial biofilms represent a promising opportunity for engineering of microbial communities. However, our ability to control spatial structure in biofilms remains limited. Here we engineer Escherichia coli with a light-activated transcriptional promoter (pDawn) to optically regulate expression of an adhesin gene (Ag43). When illuminated with patterned blue light, long-term viable biofilms with spatial resolution down to 25 μm can be formed on a variety of substrates and inside enclosed culture chambers without the need for surface pretreatment. A biophysical model suggests that the patterning mechanism involves stimulation of transiently surface-adsorbed cells, lending evidence to a previously proposed role of adhesin expression during natural biofilm maturation. Overall, this tool-termed "Biofilm Lithography"-has distinct advantages over existing cell-depositing/patterning methods and provides the ability to grow structured biofilms, with applications toward an improved understanding of natural biofilm communities, as well as the engineering of living biomaterials and bottom-up approaches to microbial consortia design.}, } @article {pmid29555778, year = {2018}, author = {Funaro, CF and Böröczky, K and Vargo, EL and Schal, C}, title = {Identification of a queen and king recognition pheromone in the subterranean termite Reticulitermes flavipes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {3888-3893}, pmid = {29555778}, issn = {1091-6490}, mesh = {Alkanes/chemistry/metabolism ; Animals ; Behavior, Animal ; Biological Evolution ; Female ; Hydrocarbons/*chemistry/metabolism ; Isoptera/*chemistry/genetics/*physiology ; Male ; Pheromones/*chemistry/metabolism ; Social Dominance ; }, abstract = {Chemical communication is fundamental to success in social insect colonies. Species-, colony-, and caste-specific blends of cuticular hydrocarbons (CHCs) and other chemicals have been well documented as pheromones, mediating important behavioral and physiological aspects of social insects. More specifically, royal pheromones used by queens (and kings in termites) enable workers to recognize and care for these vital individuals and maintain the reproductive division of labor. In termites, however, no royal-recognition pheromones have been identified to date. In the current study, solvent extracts of the subterranean termite Reticulitermes flavipes were analyzed to assess differences in cuticular compounds among castes. We identified a royal-specific hydrocarbon-heneicosane-and several previously unreported and highly royal enriched long-chain alkanes. When applied to glass dummies, heneicosane elicited worker behavioral responses identical to those elicited by live termite queens, including increased vibratory shaking and antennation. Further, the behavioral effects of heneicosane were amplified when presented with nestmate termite workers' cuticular extracts, underscoring the importance of chemical context in termite royal recognition. Thus, heneicosane is a royal-recognition pheromone that is active in both queens and kings of R. flavipes The use of heneicosane as a queen and king recognition pheromone by termites suggests that CHCs evolved as royal pheromones ∼150 million years ago, ∼50 million years before their first use as queen-recognition pheromones in social Hymenoptera. We therefore infer that termites and social Hymenoptera convergently evolved the use of these ubiquitous compounds in royal recognition.}, } @article {pmid29555777, year = {2018}, author = {Holland, SJ and Berghuis, LM and King, JJ and Iyer, LM and Sikora, K and Fifield, H and Peter, S and Quinlan, EM and Sugahara, F and Shingate, P and Trancoso, I and Iwanami, N and Temereva, E and Strohmeier, C and Kuratani, S and Venkatesh, B and Evanno, G and Aravind, L and Schorpp, M and Larijani, M and Boehm, T}, title = {Expansions, diversification, and interindividual copy number variations of AID/APOBEC family cytidine deaminase genes in lampreys.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3211-E3220}, pmid = {29555777}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {APOBEC-1 Deaminase/chemistry/*genetics/immunology ; Amino Acid Sequence ; Animals ; Cytidine Deaminase/chemistry/*classification/*genetics/immunology ; *DNA Copy Number Variations ; High-Throughput Nucleotide Sequencing ; Lampreys/*genetics ; Lymphocytes/*immunology ; Protein Conformation ; Receptors, Antigen/classification/*genetics ; Sequence Homology ; Whole Genome Sequencing ; }, abstract = {Cytidine deaminases of the AID/APOBEC family catalyze C-to-U nucleotide transitions in mRNA or DNA. Members of the APOBEC3 branch are involved in antiviral defense, whereas AID contributes to diversification of antibody repertoires in jawed vertebrates via somatic hypermutation, gene conversion, and class switch recombination. In the extant jawless vertebrate, the lamprey, two members of the AID/APOBEC family are implicated in the generation of somatic diversity of the variable lymphocyte receptors (VLRs). Expression studies linked CDA1 and CDA2 genes to the assembly of VLRA/C genes in T-like cells and the VLRB genes in B-like cells, respectively. Here, we identify and characterize several CDA1-like genes in the larvae of different lamprey species and demonstrate that these encode active cytidine deaminases. Structural comparisons of the CDA1 variants highlighted substantial differences in surface charge; this observation is supported by our finding that the enzymes require different conditions and substrates for optimal activity in vitro. Strikingly, we also found that the number of CDA-like genes present in individuals of the same species is variable. Nevertheless, irrespective of the number of different CDA1-like genes present, all lamprey larvae have at least one functional CDA1-related gene encoding an enzyme with predicted structural and chemical features generally comparable to jawed vertebrate AID. Our findings suggest that, similar to APOBEC3 branch expansion in jawed vertebrates, the AID/APOBEC family has undergone substantial diversification in lamprey, possibly indicative of multiple distinct biological roles.}, } @article {pmid29555776, year = {2018}, author = {Aime, S and Ramos, L and Cipelletti, L}, title = {Microscopic dynamics and failure precursors of a gel under mechanical load.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3587-3592}, pmid = {29555776}, issn = {1091-6490}, abstract = {Material failure is ubiquitous, with implications from geology to everyday life and material science. It often involves sudden, unpredictable events, with little or no macroscopically detectable precursors. A deeper understanding of the microscopic mechanisms eventually leading to failure is clearly required, but experiments remain scarce. Here, we show that the microscopic dynamics of a colloidal gel, a model network-forming system, exhibit dramatic changes that precede its macroscopic failure by thousands of seconds. Using an original setup coupling light scattering and rheology, we simultaneously measure the macroscopic deformation and the microscopic dynamics of the gel, while applying a constant shear stress. We show that the network failure is preceded by qualitative and quantitative changes of the dynamics, from reversible particle displacements to a burst of irreversible plastic rearrangements.}, } @article {pmid29555775, year = {2018}, author = {Lee, YJ and Dai, N and Walsh, SE and Müller, S and Fraser, ME and Kauffman, KM and Guan, C and Corrêa, IR and Weigele, PR}, title = {Identification and biosynthesis of thymidine hypermodifications in the genomic DNA of widespread bacterial viruses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3116-E3125}, pmid = {29555775}, issn = {1091-6490}, mesh = {Bacteria/*metabolism ; Bacterial Infections/*microbiology ; Bacterial Proteins/*metabolism ; Bacteriophages/*genetics/growth & development/metabolism ; DNA, Viral/*biosynthesis ; Genome, Viral ; Thymidine/*chemistry ; Uridine/*chemistry ; }, abstract = {Certain viruses of bacteria (bacteriophages) enzymatically hypermodify their DNA to protect their genetic material from host restriction endonuclease-mediated cleavage. Historically, it has been known that virion DNAs from the Delftia phage ΦW-14 and the Bacillus phage SP10 contain the hypermodified pyrimidines α-putrescinylthymidine and α-glutamylthymidine, respectively. These bases derive from the modification of 5-hydroxymethyl-2'-deoxyuridine (5-hmdU) in newly replicated phage DNA via a pyrophosphorylated intermediate. Like ΦW-14 and SP10, the Pseudomonas phage M6 and the Salmonella phage ViI encode kinase homologs predicted to phosphorylate 5-hmdU DNA but have uncharacterized nucleotide content [Iyer et al. (2013) Nucleic Acids Res 41:7635-7655]. We report here the discovery and characterization of two bases, 5-(2-aminoethoxy)methyluridine (5-NeOmdU) and 5-(2-aminoethyl)uridine (5-NedU), in the virion DNA of ViI and M6 phages, respectively. Furthermore, we show that recombinant expression of five gene products encoded by phage ViI is sufficient to reconstitute the formation of 5-NeOmdU in vitro. These findings point to an unexplored diversity of DNA modifications and the underlying biochemistry of their formation.}, } @article {pmid29555774, year = {2018}, author = {Lu, J and Zheliuk, O and Chen, Q and Leermakers, I and Hussey, NE and Zeitler, U and Ye, J}, title = {Full superconducting dome of strong Ising protection in gated monolayer WS2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3551-3556}, pmid = {29555774}, issn = {1091-6490}, abstract = {Many recent studies show that superconductivity not only exists in atomically thin monolayers but can exhibit enhanced properties such as a higher transition temperature and a stronger critical field. Nevertheless, besides being unstable in air, the weak tunability in these intrinsically metallic monolayers has limited the exploration of monolayer superconductivity, hindering their potential in electronic applications (e.g., superconductor-semiconductor hybrid devices). Here we show that using field effect gating, we can induce superconductivity in monolayer WS2 grown by chemical vapor deposition, a typical ambient-stable semiconducting transition metal dichalcogenide (TMD), and we are able to access a complete set of competing electronic phases over an unprecedented doping range from band insulator, superconductor, to a reentrant insulator at high doping. Throughout the superconducting dome, the Cooper pair spin is pinned by a strong internal spin-orbit interaction, making this material arguably the most resilient superconductor in the external magnetic field. The reentrant insulating state at positive high gating voltages is attributed to localization induced by the characteristically weak screening of the monolayer, providing insight into many dome-like superconducting phases observed in field-induced quasi-2D superconductors.}, } @article {pmid29555773, year = {2018}, author = {Nagata, MPB and Endo, K and Ogata, K and Yamanaka, K and Egashira, J and Katafuchi, N and Yamanouchi, T and Matsuda, H and Goto, Y and Sakatani, M and Hojo, T and Nishizono, H and Yotsushima, K and Takenouchi, N and Hashiyada, Y and Yamashita, K}, title = {Live births from artificial insemination of microfluidic-sorted bovine spermatozoa characterized by trajectories correlated with fertility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3087-E3096}, pmid = {29555773}, issn = {1091-6490}, mesh = {Animals ; Cattle ; Cell Separation/*methods ; Female ; Fertility/*physiology ; Fertilization in Vitro/*veterinary ; *Insemination, Artificial ; *Live Birth ; Male ; Microfluidic Analytical Techniques/*methods ; Pregnancy ; Sperm Motility ; Spermatozoa/cytology/*physiology ; }, abstract = {Selection of functional spermatozoa plays a crucial role in assisted reproduction. Passage of spermatozoa through the female reproductive tract requires progressive motility to locate the oocyte. This preferential ability to reach the fertilization site confers fertility advantage to spermatozoa. Current routine sperm selection techniques are inadequate and fail to provide conclusive evidence on the sperm characteristics that may affect fertilization. We therefore developed a selection strategy for functional and progressively motile bovine spermatozoa with high DNA integrity based on the ability to cross laminar flow streamlines in a diffuser-type microfluidic sperm sorter (DMSS). The fluid dynamics, with respect to microchannel geometry and design, are relevant in the propulsion of spermatozoa and, consequently, ultrahigh-throughput sorting. Sorted spermatozoa were assessed for kinematic parameters, acrosome reaction, mitochondrial membrane potential, and DNA integrity. Kinematic and trajectory patterns were used to identify fertility-related subpopulations: the rapid, straighter, progressive, nonsinuous pattern (PN) and the transitional, sinuous pattern (TS). In contrast to the conventional notion that the fertilizing spermatozoon is always vigorously motile and more linear, our results demonstrate that sinuous patterns are associated with fertility and correspond to truly functional spermatozoa as supported by more live births produced from predominant TS than PN subpopulation in the inseminate. Our findings ascertain the true practical application significance of microfluidic sorting of functional sperm characterized by sinuous trajectories that can serve as a behavioral sperm phenotype marker for fertility potential. More broadly, we foresee the clinical application of this sorting technology to assisted reproduction in humans.}, } @article {pmid29555772, year = {2018}, author = {Cheng, X and Kim, SY and Okamoto, H and Xin, Y and Yancopoulos, GD and Murphy, AJ and Gromada, J}, title = {Glucagon contributes to liver zonation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {17}, pages = {E4111-E4119}, pmid = {29555772}, issn = {1091-6490}, mesh = {Animals ; Gene Expression Regulation/*physiology ; Glucagon/genetics/*metabolism ; Hepatocytes/*metabolism ; Liver/*metabolism ; Mice ; Mice, Knockout ; Wnt Signaling Pathway/*physiology ; }, abstract = {Liver zonation characterizes the separation of metabolic pathways along the lobules and is required for optimal function. Wnt/β-catenin signaling controls metabolic zonation by activating genes in the perivenous hepatocytes, while suppressing genes in the periportal counterparts. We now demonstrate that glucagon opposes the actions of Wnt/β-catenin signaling on gene expression and metabolic zonation pattern. The effects were more pronounced in the periportal hepatocytes where 28% of all genes were activated by glucagon and inhibited by Wnt/β-catenin. The glucagon and Wnt/β-catenin receptors and their signaling pathways are uniformly distributed in periportal and perivenous hepatocytes and the expression is not regulated by the opposing signal. Collectively, our results show that glucagon controls gene expression and metabolic zonation in the liver through a counterplay with the Wnt/β-catenin signaling pathway.}, } @article {pmid29555771, year = {2018}, author = {Perkins, BA and Caskey, CT and Brar, P and Dec, E and Karow, DS and Kahn, AM and Hou, YC and Shah, N and Boeldt, D and Coughlin, E and Hands, G and Lavrenko, V and Yu, J and Procko, A and Appis, J and Dale, AM and Guo, L and Jönsson, TJ and Wittmann, BM and Bartha, I and Ramakrishnan, S and Bernal, A and Brewer, JB and Brewerton, S and Biggs, WH and Turpaz, Y and Venter, JC}, title = {Precision medicine screening using whole-genome sequencing and advanced imaging to identify disease risk in adults.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3686-3691}, pmid = {29555771}, issn = {1091-6490}, mesh = {Adult ; Aged ; Aged, 80 and over ; Cardiovascular Diseases/diagnostic imaging/genetics/pathology ; Disease/classification/*genetics ; Female ; *Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Image Processing, Computer-Assisted/*methods ; Male ; Middle Aged ; *Mutation ; Neoplasms/diagnostic imaging/genetics/pathology ; Nervous System Diseases/diagnostic imaging/genetics/pathology ; Precision Medicine/*methods ; Risk Assessment ; Sequence Analysis, RNA ; Whole Genome Sequencing/*methods ; Young Adult ; }, abstract = {Reducing premature mortality associated with age-related chronic diseases, such as cancer and cardiovascular disease, is an urgent priority. We report early results using genomics in combination with advanced imaging and other clinical testing to proactively screen for age-related chronic disease risk among adults. We enrolled active, symptom-free adults in a study of screening for age-related chronic diseases associated with premature mortality. In addition to personal and family medical history and other clinical testing, we obtained whole-genome sequencing (WGS), noncontrast whole-body MRI, dual-energy X-ray absorptiometry (DXA), global metabolomics, a new blood test for prediabetes (Quantose IR), echocardiography (ECHO), ECG, and cardiac rhythm monitoring to identify age-related chronic disease risks. Precision medicine screening using WGS and advanced imaging along with other testing among active, symptom-free adults identified a broad set of complementary age-related chronic disease risks associated with premature mortality and strengthened WGS variant interpretation. This and other similarly designed screening approaches anchored by WGS and advanced imaging may have the potential to extend healthy life among active adults through improved prevention and early detection of age-related chronic diseases (and their risk factors) associated with premature mortality.}, } @article {pmid29555770, year = {2018}, author = {Caforio, A and Siliakus, MF and Exterkate, M and Jain, S and Jumde, VR and Andringa, RLH and Kengen, SWM and Minnaard, AJ and Driessen, AJM and van der Oost, J}, title = {Converting Escherichia coli into an archaebacterium with a hybrid heterochiral membrane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3704-3709}, pmid = {29555770}, issn = {1091-6490}, mesh = {Archaea/*metabolism ; *Biological Evolution ; Cell Membrane/chemistry/*metabolism ; Escherichia coli/*metabolism ; Ethers/chemistry/*metabolism ; Membrane Lipids/chemistry/*metabolism ; Phospholipids/chemistry/*metabolism ; }, abstract = {One of the main differences between bacteria and archaea concerns their membrane composition. Whereas bacterial membranes are made up of glycerol-3-phosphate ester lipids, archaeal membranes are composed of glycerol-1-phosphate ether lipids. Here, we report the construction of a stable hybrid heterochiral membrane through lipid engineering of the bacterium Escherichia coli By boosting isoprenoid biosynthesis and heterologous expression of archaeal ether lipid biosynthesis genes, we obtained a viable E. coli strain of which the membranes contain archaeal lipids with the expected stereochemistry. It has been found that the archaeal lipid biosynthesis enzymes are relatively promiscuous with respect to their glycerol phosphate backbone and that E. coli has the unexpected potential to generate glycerol-1-phosphate. The unprecedented level of 20-30% archaeal lipids in a bacterial cell has allowed for analyzing the effect on the mixed-membrane cell's phenotype. Interestingly, growth rates are unchanged, whereas the robustness of cells with a hybrid heterochiral membrane appeared slightly increased. The implications of these findings for evolutionary scenarios are discussed.}, } @article {pmid29555769, year = {2018}, author = {Kosuge, K and Tokutsu, R and Kim, E and Akimoto, S and Yokono, M and Ueno, Y and Minagawa, J}, title = {LHCSR1-dependent fluorescence quenching is mediated by excitation energy transfer from LHCII to photosystem I in Chlamydomonas reinhardtii.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3722-3727}, pmid = {29555769}, issn = {1091-6490}, mesh = {Algal Proteins/chemistry/genetics/metabolism ; Chlamydomonas reinhardtii/*metabolism/radiation effects ; Electron Transport ; Energy Transfer ; *Fluorescence ; Hydrogen-Ion Concentration ; Light ; Light-Harvesting Protein Complexes/chemistry/genetics/*metabolism ; Photosynthesis ; Photosystem I Protein Complex/chemistry/genetics/*metabolism ; Photosystem II Protein Complex/chemistry/genetics/*metabolism ; Thylakoids/chemistry/metabolism ; }, abstract = {Photosynthetic organisms are frequently exposed to light intensities that surpass the photosynthetic electron transport capacity. Under these conditions, the excess absorbed energy can be transferred from excited chlorophyll in the triplet state (3Chl*) to molecular O2, which leads to the production of harmful reactive oxygen species. To avoid this photooxidative stress, photosynthetic organisms must respond to excess light. In the green alga Chlamydomonas reinhardtii, the fastest response to high light is nonphotochemical quenching, a process that allows safe dissipation of the excess energy as heat. The two proteins, UV-inducible LHCSR1 and blue light-inducible LHCSR3, appear to be responsible for this function. While the LHCSR3 protein has been intensively studied, the role of LHCSR1 has been only partially elucidated. To investigate the molecular functions of LHCSR1 in C. reinhardtii, we performed biochemical and spectroscopic experiments and found that the protein mediates excitation energy transfer from light-harvesting complexes for Photosystem II (LHCII) to Photosystem I (PSI), rather than Photosystem II, at a low pH. This altered excitation transfer allows remarkable fluorescence quenching under high light. Our findings suggest that there is a PSI-dependent photoprotection mechanism that is facilitated by LHCSR1.}, } @article {pmid29555768, year = {2018}, author = {Reilein, A and Melamed, D and Tavaré, S and Kalderon, D}, title = {Division-independent differentiation mandates proliferative competition among stem cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3182-E3191}, pmid = {29555768}, issn = {1091-6490}, support = {R01 GM079351/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Cell Differentiation ; *Cell Lineage ; *Cell Proliferation ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*cytology/metabolism ; Female ; Ovarian Follicle/*cytology/metabolism ; Stem Cell Niche/*physiology ; Stem Cells/*cytology/metabolism ; }, abstract = {Cancer-initiating gatekeeper mutations that arise in stem cells would be especially potent if they stabilize and expand an affected stem cell lineage. It is therefore important to understand how different stem cell organization strategies promote or prevent variant stem cell amplification in response to different types of mutation, including those that activate proliferation. Stem cell numbers can be maintained constant while producing differentiated products through individually asymmetrical division outcomes or by population asymmetry strategies in which individual stem cell lineages necessarily compete for niche space. We considered alternative mechanisms underlying population asymmetry and used quantitative modeling to predict starkly different consequences of altering proliferation rate: A variant, faster proliferating mutant stem cell should compete better only when stem cell division and differentiation are independent processes. For most types of stem cells, it has not been possible to ascertain experimentally whether division and differentiation are coupled. However, Drosophila follicle stem cells (FSCs) provided a favorable system with which to investigate population asymmetry mechanisms and also for measuring the impact of altered proliferation on competition. We found from detailed cell lineage studies that division and differentiation of an individual FSC are not coupled. We also found that FSC representation, reflecting maintenance and amplification, was highly responsive to genetic changes that altered only the rate of FSC proliferation. The FSC paradigm therefore provides definitive experimental evidence for the general principle that relative proliferation rate will always be a major determinant of competition among stem cells specifically when stem cell division and differentiation are independent.}, } @article {pmid29555767, year = {2018}, author = {Imamura, K and Yoshitane, H and Hattori, K and Yamaguchi, M and Yoshida, K and Okubo, T and Naguro, I and Ichijo, H and Fukada, Y}, title = {ASK family kinases mediate cellular stress and redox signaling to circadian clock.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3646-3651}, pmid = {29555767}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal ; Circadian Clocks/*physiology ; MAP Kinase Kinase Kinase 5/*physiology ; MAP Kinase Kinase Kinases/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Osmotic Pressure ; Oxidation-Reduction ; Phosphorylation ; Protein Processing, Post-Translational ; Proteomics ; Signal Transduction ; }, abstract = {Daily rhythms of behaviors and physiologies are generated by the circadian clock, which is composed of clock genes and the encoded proteins forming transcriptional/translational feedback loops (TTFLs). The circadian clock is a self-sustained oscillator and flexibly responds to various time cues to synchronize with environmental 24-h cycles. However, the key molecule that transmits cellular stress to the circadian clockwork is unknown. Here we identified apoptosis signal-regulating kinase (ASK), a member of the MAPKKK family, as an essential mediator determining the circadian period and phase of cultured cells in response to osmotic changes of the medium. The physiological impact of ASK signaling was demonstrated by a response of the clock to changes in intracellular redox states. Intriguingly, the TTFLs drive rhythmic expression of Ask genes, indicating ASK-mediated association of the TTFLs with intracellular redox. In behavioral analysis, Ask1, Ask2, and Ask3 triple-KO mice exhibited compromised light responses of the circadian period and phase in their activity rhythms. LC-MS/MS-based proteomic analysis identified a series of ASK-dependent and osmotic stress-responsive phosphorylations of proteins, among which CLOCK, a key component of the molecular clockwork, was phosphorylated at Thr843 or Ser845 in the carboxyl-terminal region. These findings reveal the ASK-dependent stress response as an underlying mechanism of circadian clock flexibility.}, } @article {pmid29555766, year = {2018}, author = {Anderson, ND and Dell, GS}, title = {The role of consolidation in learning context-dependent phonotactic patterns in speech and digital sequence production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3617-3622}, pmid = {29555766}, issn = {1091-6490}, support = {R01 HD086099/HD/NICHD NIH HHS/United States ; }, mesh = {Conditioning, Classical ; Humans ; *Phonetics ; *Psycholinguistics ; Signal Processing, Computer-Assisted/*instrumentation ; Speech Perception/*physiology ; Verbal Learning/*physiology ; }, abstract = {Speakers implicitly learn novel phonotactic patterns by producing strings of syllables. The learning is revealed in their speech errors. First-order patterns, such as "/f/ must be a syllable onset," can be distinguished from contingent, or second-order, patterns, such as "/f/ must be an onset if the vowel is /a/, but a coda if the vowel is /o/." A metaanalysis of 19 experiments clearly demonstrated that first-order patterns affect speech errors to a very great extent in a single experimental session, but second-order vowel-contingent patterns only affect errors on the second day of testing, suggesting the need for a consolidation period. Two experiments tested an analogue to these studies involving sequences of button pushes, with fingers as "consonants" and thumbs as "vowels." The button-push errors revealed two of the key speech-error findings: first-order patterns are learned quickly, but second-order thumb-contingent patterns are only strongly revealed in the errors on the second day of testing. The influence of computational complexity on the implicit learning of phonotactic patterns in speech production may be a general feature of sequence production.}, } @article {pmid29555765, year = {2018}, author = {Mattle, D and Kuhn, B and Aebi, J and Bedoucha, M and Kekilli, D and Grozinger, N and Alker, A and Rudolph, MG and Schmid, G and Schertler, GFX and Hennig, M and Standfuss, J and Dawson, RJP}, title = {Ligand channel in pharmacologically stabilized rhodopsin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3640-3645}, pmid = {29555765}, issn = {1091-6490}, mesh = {Animals ; Cells, Cultured ; *Drug Design ; Humans ; Ligands ; Mice ; Models, Molecular ; Pharmaceutical Preparations/*administration & dosage/metabolism ; Protein Conformation/*drug effects ; Protein Stability/*drug effects ; Receptors, G-Protein-Coupled/*chemistry/metabolism ; Rhodopsin/*chemistry/metabolism ; }, abstract = {In the degenerative eye disease retinitis pigmentosa (RP), protein misfolding leads to fatal consequences for cell metabolism and rod and cone cell survival. To stop disease progression, a therapeutic approach focuses on stabilizing inherited protein mutants of the G protein-coupled receptor (GPCR) rhodopsin using pharmacological chaperones (PC) that improve receptor folding and trafficking. In this study, we discovered stabilizing nonretinal small molecules by virtual and thermofluor screening and determined the crystal structure of pharmacologically stabilized opsin at 2.4 Å resolution using one of the stabilizing hits (S-RS1). Chemical modification of S-RS1 and further structural analysis revealed the core binding motif of this class of rhodopsin stabilizers bound at the orthosteric binding site. Furthermore, previously unobserved conformational changes are visible at the intradiscal side of the seven-transmembrane helix bundle. A hallmark of this conformation is an open channel connecting the ligand binding site with the membrane and the intradiscal lumen of rod outer segments. Sufficient in size, the passage permits the exchange of hydrophobic ligands such as retinal. The results broaden our understanding of rhodopsin's conformational flexibility and enable therapeutic drug intervention against rhodopsin-related retinitis pigmentosa.}, } @article {pmid29555764, year = {2018}, author = {Subramanian, P and Pirbadian, S and El-Naggar, MY and Jensen, GJ}, title = {Ultrastructure of Shewanella oneidensis MR-1 nanowires revealed by electron cryotomography.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3246-E3255}, pmid = {29555764}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cryoelectron Microscopy/*methods ; Cytochromes/*metabolism ; Electron Transport ; *Electrons ; Microscopy, Fluorescence ; Nanowires/*ultrastructure ; Shewanella/*metabolism/*ultrastructure ; }, abstract = {Bacterial nanowires have garnered recent interest as a proposed extracellular electron transfer (EET) pathway that links the bacterial electron transport chain to solid-phase electron acceptors away from the cell. Recent studies showed that Shewanella oneidensis MR-1 produces outer membrane (OM) and periplasmic extensions that contain EET components and hinted at their possible role as bacterial nanowires. However, their fine structure and distribution of cytochrome electron carriers under native conditions remained unclear, making it difficult to evaluate the potential electron transport (ET) mechanism along OM extensions. Here, we report high-resolution images of S. oneidensis OM extensions, using electron cryotomography (ECT). We developed a robust method for fluorescence light microscopy imaging of OM extension growth on electron microscopy grids and used correlative light and electron microscopy to identify and image the same structures by ECT. Our results reveal that S. oneidensis OM extensions are dynamic chains of interconnected outer membrane vesicles (OMVs) with variable dimensions, curvature, and extent of tubulation. Junction densities that potentially stabilize OMV chains are seen between neighboring vesicles in cryotomograms. By comparing wild type and a cytochrome gene deletion mutant, our ECT results provide the likely positions and packing of periplasmic and outer membrane proteins consistent with cytochromes. Based on the observed cytochrome packing density, we propose a plausible ET path along the OM extensions involving a combination of direct hopping and cytochrome diffusion. A mean-field calculation, informed by the observed ECT cytochrome density, supports this proposal by revealing ET rates on par with a fully packed cytochrome network.}, } @article {pmid29555763, year = {2018}, author = {Zanca, T and Pellegrini, F and Santoro, GE and Tosatti, E}, title = {Frictional lubricity enhanced by quantum mechanics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3547-3550}, pmid = {29555763}, issn = {1091-6490}, abstract = {The quantum motion of nuclei, generally ignored in the physics of sliding friction, can affect in an important manner the frictional dissipation of a light particle forced to slide in an optical lattice. The density matrix-calculated evolution of the quantum version of the basic Prandtl-Tomlinson model, describing the dragging by an external force of a point particle in a periodic potential, shows that purely classical friction predictions can be very wrong. The strongest quantum effect occurs not for weak but for strong periodic potentials, where barriers are high but energy levels in each well are discrete, and resonant Rabi or Landau-Zener tunneling to states in the nearest well can preempt classical stick-slip with nonnegligible efficiency, depending on the forcing speed. The resulting permeation of otherwise unsurmountable barriers is predicted to cause quantum lubricity, a phenomenon which we expect should be observable in the recently implemented sliding cold ion experiments.}, } @article {pmid29555762, year = {2018}, author = {Chavez, A and Pruitt, BW and Tuttle, M and Shapiro, RS and Cecchi, RJ and Winston, J and Turczyk, BM and Tung, M and Collins, JJ and Church, GM}, title = {Precise Cas9 targeting enables genomic mutation prevention.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3669-3673}, pmid = {29555762}, issn = {1091-6490}, support = {P50 HG005550/HG/NHGRI NIH HHS/United States ; RM1 HG008525/HG/NHGRI NIH HHS/United States ; T32 CA009216/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibiotics, Antitubercular/pharmacology ; *CRISPR-Cas Systems ; Drug Resistance, Bacterial/*genetics ; Escherichia coli/*genetics/metabolism ; Genome, Bacterial ; Genomics/*methods ; Mice ; *Mutation ; *RNA, Guide ; Rifampin/pharmacology ; }, abstract = {Here, we present a generalized method of guide RNA "tuning" that enables Cas9 to discriminate between two target sites that differ by a single-nucleotide polymorphism. We employ our methodology to generate an in vivo mutation prevention system in which Cas9 actively restricts the occurrence of undesired gain-of-function mutations within a population of engineered organisms. We further demonstrate that the system is scalable to a multitude of targets and that the general tuning and prevention concepts are portable across engineered Cas9 variants and Cas9 orthologs. Finally, we show that the mutation prevention system maintains robust activity even when placed within the complex environment of the mouse gastrointestinal tract.}, } @article {pmid29555761, year = {2018}, author = {Nie, C and Wang, H and Wang, R and Ginsburg, D and Chen, XW}, title = {Dimeric sorting code for concentrative cargo selection by the COPII coat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3155-E3162}, pmid = {29555761}, issn = {1091-6490}, support = {P01 HL057346/HL/NHLBI NIH HHS/United States ; R01 HL039693/HL/NHLBI NIH HHS/United States ; R35 HL135793/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {COP-Coated Vesicles/*metabolism ; Endoplasmic Reticulum/*metabolism ; Golgi Apparatus/*metabolism ; HeLa Cells ; Humans ; Mannose-Binding Lectins/*chemistry/genetics/*metabolism ; Membrane Proteins/*chemistry/genetics/*metabolism ; Mutation ; Protein Multimerization ; Protein Transport ; Secretory Pathway ; }, abstract = {The flow of cargo vesicles along the secretory pathway requires concerted action among various regulators. The COPII complex, assembled by the activated SAR1 GTPases on the surface of the endoplasmic reticulum, orchestrates protein interactions to package cargos and generate transport vesicles en route to the Golgi. The dynamic nature of COPII, however, hinders analysis with conventional biochemical assays. Here we apply proximity-dependent biotinylation labeling to capture the dynamics of COPII transport in cells. When SAR1B was fused with a promiscuous biotin ligase, BirA*, the fusion protein SAR1B-BirA* biotinylates and thus enables the capture of COPII machinery and cargos in a GTP-dependent manner. Biochemical and pulse-chase imaging experiments demonstrate that the COPII coat undergoes a dynamic cycle of engagement-disengagement with the transmembrane cargo receptor LMAN1/ERGIC53. LMAN1 undergoes a process of concentrative sorting by the COPII coat, via a dimeric sorting code generated by oligomerization of the cargo receptor. Similar oligomerization events have been observed with other COPII sorting signals, suggesting that dimeric/multimeric sorting codes may serve as a general mechanism to generate selectivity of cargo sorting.}, } @article {pmid29555760, year = {2018}, author = {Sheehan, O and Watts, J and Gray, RD and Atkinson, QD}, title = {Coevolution of landesque capital intensive agriculture and sociopolitical hierarchy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3628-3633}, pmid = {29555760}, issn = {1091-6490}, abstract = {One of the defining trends of the Holocene has been the emergence of complex societies. Two essential features of complex societies are intensive resource use and sociopolitical hierarchy. Although it is widely agreed that these two phenomena are associated cross-culturally and have both contributed to the rise of complex societies, the causality underlying their relationship has been the subject of longstanding debate. Materialist theories of cultural evolution tend to view resource intensification as driving the development of hierarchy, but the reverse order of causation has also been advocated, along with a range of intermediate views. Phylogenetic methods have the potential to test between these different causal models. Here we report the results of a phylogenetic study that modeled the coevolution of one type of resource intensification-the development of landesque capital intensive agriculture-with political complexity and social stratification in a sample of 155 Austronesian-speaking societies. We found support for the coevolution of landesque capital with both political complexity and social stratification, but the contingent and nondeterministic nature of both of these relationships was clear. There was no indication that intensification was the "prime mover" in either relationship. Instead, the relationship between intensification and social stratification was broadly reciprocal, whereas political complexity was more of a driver than a result of intensification. These results challenge the materialist view and emphasize the importance of both material and social factors in the evolution of complex societies, as well as the complex and multifactorial nature of cultural evolution.}, } @article {pmid29555759, year = {2018}, author = {Lin, PP and Jaeger, AJ and Wu, TY and Xu, SC and Lee, AS and Gao, F and Chen, PW and Liao, JC}, title = {Construction and evolution of an Escherichia coli strain relying on nonoxidative glycolysis for sugar catabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3538-3546}, pmid = {29555759}, issn = {1091-6490}, mesh = {Acetyl Coenzyme A/*metabolism ; Carbohydrate Metabolism ; Energy Metabolism ; Escherichia coli/classification/genetics/*growth & development/*metabolism ; Fermentation ; Glucose/*metabolism ; *Glycolysis ; *Metabolic Engineering ; Mutation ; }, abstract = {The Embden-Meyerhoff-Parnas (EMP) pathway, commonly known as glycolysis, represents the fundamental biochemical infrastructure for sugar catabolism in almost all organisms, as it provides key components for biosynthesis, energy metabolism, and global regulation. EMP-based metabolism synthesizes three-carbon (C3) metabolites before two-carbon (C2) metabolites and must emit one CO2 in the synthesis of the C2 building block, acetyl-CoA, a precursor for many industrially important products. Using rational design, genome editing, and evolution, here we replaced the native glycolytic pathways in Escherichia coli with the previously designed nonoxidative glycolysis (NOG), which bypasses initial C3 formation and directly generates stoichiometric amounts of C2 metabolites. The resulting strain, which contains 11 gene overexpressions, 10 gene deletions by design, and more than 50 genomic mutations (including 3 global regulators) through evolution, grows aerobically in glucose minimal medium but can ferment anaerobically to products with nearly complete carbon conservation. We confirmed that the strain metabolizes glucose through NOG by 13C tracer experiments. This redesigned E. coli strain represents a different approach for carbon catabolism and may serve as a useful platform for bioproduction.}, } @article {pmid29555758, year = {2018}, author = {Law, BE and Hudiburg, TW and Berner, LT and Kent, JJ and Buotte, PC and Harmon, ME}, title = {Land use strategies to mitigate climate change in carbon dense temperate forests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3663-3668}, pmid = {29555758}, issn = {1091-6490}, mesh = {*Agriculture ; Carbon/*metabolism ; *Climate Change ; *Conservation of Natural Resources ; *Ecosystem ; Fires ; *Forestry ; *Forests ; }, abstract = {Strategies to mitigate carbon dioxide emissions through forestry activities have been proposed, but ecosystem process-based integration of climate change, enhanced CO2, disturbance from fire, and management actions at regional scales are extremely limited. Here, we examine the relative merits of afforestation, reforestation, management changes, and harvest residue bioenergy use in the Pacific Northwest. This region represents some of the highest carbon density forests in the world, which can store carbon in trees for 800 y or more. Oregon's net ecosystem carbon balance (NECB) was equivalent to 72% of total emissions in 2011-2015. By 2100, simulations show increased net carbon uptake with little change in wildfires. Reforestation, afforestation, lengthened harvest cycles on private lands, and restricting harvest on public lands increase NECB 56% by 2100, with the latter two actions contributing the most. Resultant cobenefits included water availability and biodiversity, primarily from increased forest area, age, and species diversity. Converting 127,000 ha of irrigated grass crops to native forests could decrease irrigation demand by 233 billion m3⋅y-1 Utilizing harvest residues for bioenergy production instead of leaving them in forests to decompose increased emissions in the short-term (50 y), reducing mitigation effectiveness. Increasing forest carbon on public lands reduced emissions compared with storage in wood products because the residence time is more than twice that of wood products. Hence, temperate forests with high carbon densities and lower vulnerability to mortality have substantial potential for reducing forest sector emissions. Our analysis framework provides a template for assessments in other temperate regions.}, } @article {pmid29555757, year = {2018}, author = {Guo, Y and Tikhonov, M and Brenner, MP}, title = {Local growth rules can maintain metabolically efficient spatial structure throughout growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3593-3598}, pmid = {29555757}, issn = {1091-6490}, mesh = {Bacteria/*growth & development/*metabolism ; Biochemical Phenomena ; *Biological Phenomena ; *Environment ; *Models, Biological ; }, abstract = {A ubiquitous feature of bacterial communities is the existence of spatial structures. These are often coupled to metabolism, whereby the spatial organization can improve chemical reaction efficiency. However, it is not clear whether or how a desired colony configuration, for example, one that optimizes some overall global objective, could be achieved by individual cells that do not have knowledge of their positions or of the states of all other cells. By using a model which consists of cells producing enzymes that catalyze coupled metabolic reactions, we show that simple, local rules can be sufficient for achieving a global, community-level goal. In particular, even though the optimal configuration varies with colony size, we demonstrate that cells regulating their relative enzyme levels based solely on local metabolite concentrations can maintain the desired overall spatial structure during colony growth. We also show that these rules can be very simple and hence easily implemented by cells. Our framework also predicts scenarios where additional signaling mechanisms may be required.}, } @article {pmid29555756, year = {2018}, author = {Raiteri, BJ and Cresswell, AG and Lichtwark, GA}, title = {Muscle-tendon length and force affect human tibialis anterior central aponeurosis stiffness in vivo.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3097-E3105}, pmid = {29555756}, issn = {1091-6490}, mesh = {Adult ; Aponeurosis/diagnostic imaging/*physiology ; Biomechanical Phenomena ; Female ; Humans ; Isometric Contraction ; Male ; Muscle Contraction/*physiology ; Muscle, Skeletal/diagnostic imaging/*physiology ; Tendons/diagnostic imaging/*physiology ; Tibia/diagnostic imaging/*physiology ; Ultrasonography ; }, abstract = {The factors that drive variable aponeurosis behaviors in active versus passive muscle may alter the longitudinal stiffness of the aponeurosis during contraction, which may change the fascicle strains for a given muscle force. However, it remains unknown whether these factors can drive variable aponeurosis behaviors across different muscle-tendon unit (MTU) lengths and influence the subsequent fascicle strains during contraction. Here, we used ultrasound and elastography techniques to examine in vivo muscle fascicle behavior and central aponeurosis deformations of human tibialis anterior (TA) during force-matched voluntary isometric dorsiflexion contractions at three MTU lengths. We found that increases in TA MTU length increased both the length and apparent longitudinal stiffness of the central aponeurosis at low and moderate muscle forces (P < 0.01). We also found that increased aponeurosis stiffness was directly related to reduced magnitudes of TA muscle fascicle shortening for the same change in force (P < 0.01). The increase in slope and shift to longer overall lengths of the active aponeurosis force-length relationship as MTU length increased was likely due to a combination of parallel lengthening of aponeurosis and greater transverse aponeurosis strains. This study provides in vivo evidence that human aponeurosis stiffness is increased from low to moderate forces and that the fascicle strains for a given muscle force are MTU length dependent. Further testing is warranted to determine whether MTU length-dependent stiffness is a fundamental property of the aponeurosis in pennate muscles and evaluate whether this property can enhance muscle performance.}, } @article {pmid29555755, year = {2018}, author = {Guo, J and Tang, HW and Li, J and Perrimon, N and Yan, D}, title = {Xio is a component of the Drosophila sex determination pathway and RNA N6-methyladenosine methyltransferase complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3674-3679}, pmid = {29555755}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adenosine/*analogs & derivatives/metabolism ; Alternative Splicing ; Animals ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/*genetics/growth & development/metabolism ; Female ; Male ; Methyltransferases/genetics/*metabolism ; RNA/genetics/*metabolism ; RNA Precursors/genetics/*metabolism ; RNA-Binding Proteins/genetics/metabolism ; Sex Determination Processes/*genetics ; }, abstract = {N6-methyladenosine (m6A), the most abundant chemical modification in eukaryotic mRNA, has been implicated in Drosophila sex determination by modifying Sex-lethal (Sxl) pre-mRNA and facilitating its alternative splicing. Here, we identify a sex determination gene, CG7358, and rename it xio according to its loss-of-function female-to-male transformation phenotype. xio encodes a conserved ubiquitous nuclear protein of unknown function. We show that Xio colocalizes and interacts with all previously known m6A writer complex subunits (METTL3, METTL14, Fl(2)d/WTAP, Vir/KIAA1429, and Nito/Rbm15) and that loss of xio is associated with phenotypes that resemble other m6A factors, such as sexual transformations, Sxl splicing defect, held-out wings, flightless flies, and reduction of m6A levels. Thus, Xio encodes a member of the m6A methyltransferase complex involved in mRNA modification. Since its ortholog ZC3H13 (or KIAA0853) also associates with several m6A writer factors, the function of Xio in the m6A pathway is likely evolutionarily conserved.}, } @article {pmid29555754, year = {2018}, author = {Hertzberg, VS and Weiss, H and Elon, L and Si, W and Norris, SL and , }, title = {Behaviors, movements, and transmission of droplet-mediated respiratory diseases during transcontinental airline flights.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3623-3627}, pmid = {29555754}, issn = {1091-6490}, mesh = {*Air Movements ; *Air Travel ; *Aircraft ; Communicable Diseases/*psychology/*transmission ; Computer Simulation ; DNA, Viral/analysis/genetics ; Global Health ; *Human Activities ; Humans ; Risk Assessment ; Viruses/classification/genetics/*pathogenicity ; }, abstract = {With over 3 billion airline passengers annually, the inflight transmission of infectious diseases is an important global health concern. Over a dozen cases of inflight transmission of serious infections have been documented, and air travel can serve as a conduit for the rapid spread of newly emerging infections and pandemics. Despite sensational media stories and anecdotes, the risks of transmission of respiratory viruses in an airplane cabin are unknown. Movements of passengers and crew may facilitate disease transmission. On 10 transcontinental US flights, we chronicled behaviors and movements of individuals in the economy cabin on single-aisle aircraft. We simulated transmission during flight based on these data. Our results indicate there is low probability of direct transmission to passengers not seated in close proximity to an infectious passenger. This data-driven, dynamic network transmission model of droplet-mediated respiratory disease is unique. To measure the true pathogen burden, our team collected 229 environmental samples during the flights. Although eight flights were during Influenza season, all qPCR assays for 18 common respiratory viruses were negative.}, } @article {pmid29555753, year = {2018}, author = {Li, L and Fijneman, AJ and Kaandorp, JA and Aizenberg, J and Noorduin, WL}, title = {Directed nucleation and growth by balancing local supersaturation and substrate/nucleus lattice mismatch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3575-3580}, pmid = {29555753}, issn = {1091-6490}, abstract = {Controlling nucleation and growth is crucial in biological and artificial mineralization and self-assembly processes. The nucleation barrier is determined by the chemistry of the interfaces at which crystallization occurs and local supersaturation. Although chemically tailored substrates and lattice mismatches are routinely used to modify energy landscape at the substrate/nucleus interface and thereby steer heterogeneous nucleation, strategies to combine this with control over local supersaturations have remained virtually unexplored. Here we demonstrate simultaneous control over both parameters to direct the positioning and growth direction of mineralizing compounds on preselected polymorphic substrates. We exploit the polymorphic nature of calcium carbonate (CaCO3) to locally manipulate the carbonate concentration and lattice mismatch between the nucleus and substrate, such that barium carbonate (BaCO3) and strontium carbonate (SrCO3) nucleate only on specific CaCO3 polymorphs. Based on this approach we position different materials and shapes on predetermined CaCO3 polymorphs in sequential steps, and guide the growth direction using locally created supersaturations. These results shed light on nature's remarkable mineralization capabilities and outline fabrication strategies for advanced materials, such as ceramics, photonic structures, and semiconductors.}, } @article {pmid29555752, year = {2018}, author = {Dai, L and Best, V and Shinn-Cunningham, BG}, title = {Sensorineural hearing loss degrades behavioral and physiological measures of human spatial selective auditory attention.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3286-E3295}, pmid = {29555752}, issn = {1091-6490}, support = {R01 DC013825/DC/NIDCD NIH HHS/United States ; R01 DC015760/DC/NIDCD NIH HHS/United States ; }, mesh = {Adult ; Attention/*physiology ; Auditory Perception/*physiology ; Auditory Threshold/*physiology ; Case-Control Studies ; *Discrimination (Psychology) ; Female ; Hearing Loss, Sensorineural/*physiopathology/*psychology ; Humans ; Male ; Middle Aged ; Models, Theoretical ; Space Perception/*physiology ; Young Adult ; }, abstract = {Listeners with sensorineural hearing loss often have trouble understanding speech amid other voices. While poor spatial hearing is often implicated, direct evidence is weak; moreover, studies suggest that reduced audibility and degraded spectrotemporal coding may explain such problems. We hypothesized that poor spatial acuity leads to difficulty deploying selective attention, which normally filters out distracting sounds. In listeners with normal hearing, selective attention causes changes in the neural responses evoked by competing sounds, which can be used to quantify the effectiveness of attentional control. Here, we used behavior and electroencephalography to explore whether control of selective auditory attention is degraded in hearing-impaired (HI) listeners. Normal-hearing (NH) and HI listeners identified a simple melody presented simultaneously with two competing melodies, each simulated from different lateral angles. We quantified performance and attentional modulation of cortical responses evoked by these competing streams. Compared with NH listeners, HI listeners had poorer sensitivity to spatial cues, performed more poorly on the selective attention task, and showed less robust attentional modulation of cortical responses. Moreover, across NH and HI individuals, these measures were correlated. While both groups showed cortical suppression of distracting streams, this modulation was weaker in HI listeners, especially when attending to a target at midline, surrounded by competing streams. These findings suggest that hearing loss interferes with the ability to filter out sound sources based on location, contributing to communication difficulties in social situations. These findings also have implications for technologies aiming to use neural signals to guide hearing aid processing.}, } @article {pmid29555751, year = {2018}, author = {Krishnan, A and Iyer, LM and Holland, SJ and Boehm, T and Aravind, L}, title = {Diversification of AID/APOBEC-like deaminases in metazoa: multiplicity of clades and widespread roles in immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3201-E3210}, pmid = {29555751}, issn = {1091-6490}, mesh = {Adaptive Immunity/*immunology ; Amino Acid Sequence ; Animals ; Chlorophyta/genetics/immunology ; Cytidine Deaminase/chemistry/*classification/*genetics/immunology ; Dictyosteliida/genetics/immunology ; *Evolution, Molecular ; Host-Pathogen Interactions ; Humans ; Nucleic Acids/*genetics ; Phylogeny ; Protein Conformation ; Retroelements ; Sequence Homology ; Vertebrates/genetics/*immunology/virology ; Viruses/*pathogenicity ; }, abstract = {AID/APOBEC deaminases (AADs) convert cytidine to uridine in single-stranded nucleic acids. They are involved in numerous mutagenic processes, including those underpinning vertebrate innate and adaptive immunity. Using a multipronged sequence analysis strategy, we uncover several AADs across metazoa, dictyosteliida, and algae, including multiple previously unreported vertebrate clades, and versions from urochordates, nematodes, echinoderms, arthropods, lophotrochozoans, cnidarians, and porifera. Evolutionary analysis suggests a fundamental division of AADs early in metazoan evolution into secreted deaminases (SNADs) and classical AADs, followed by diversification into several clades driven by rapid-sequence evolution, gene loss, lineage-specific expansions, and lateral transfer to various algae. Most vertebrate AADs, including AID and APOBECs1-3, diversified in the vertebrates, whereas the APOBEC4-like clade has a deeper origin in metazoa. Positional entropy analysis suggests that several AAD clades are diversifying rapidly, especially in the positions predicted to interact with the nucleic acid target motif, and with potential viral inhibitors. Further, several AADs have evolved neomorphic metal-binding inserts, especially within loops predicted to interact with the target nucleic acid. We also observe polymorphisms, driven by alternative splicing, gene loss, and possibly intergenic recombination between paralogs. We propose that biological conflicts of AADs with viruses and genomic retroelements are drivers of rapid AAD evolution, suggesting a widespread presence of mutagenesis-based immune-defense systems. Deaminases like AID represent versions "institutionalized" from the broader array of AADs pitted in such arms races for mutagenesis of self-DNA, and similar recruitment might have independently occurred elsewhere in metazoa.}, } @article {pmid29555750, year = {2018}, author = {Sharpe, AE and Emery, KF and Inomata, T and Triadan, D and Kamenov, GD and Krigbaum, J}, title = {Earliest isotopic evidence in the Maya region for animal management and long-distance trade at the site of Ceibal, Guatemala.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3605-3610}, pmid = {29555750}, issn = {1091-6490}, mesh = {*Animal Husbandry ; Animals ; Archaeology/*history ; Carbon Radioisotopes/*analysis ; Dogs ; Guatemala ; History, Ancient ; Humans ; Livestock/*physiology ; *Marketing ; Nitrogen Radioisotopes/*analysis ; Oxygen Radioisotopes/*analysis ; Strontium Radioisotopes/analysis ; }, abstract = {This study uses a multiisotope (carbon, nitrogen, oxygen, and strontium) approach to examine early animal management in the Maya region. An analysis of faunal specimens across almost 2,000 years (1000 BC to AD 950) at the site of Ceibal, Guatemala, reveals the earliest evidence for live-traded dogs and possible captive-reared taxa in the Americas. These animals may have been procured for ceremonial functions based on their location in the monumental site core, suggesting that animal management and trade began in the Maya area to promote special events, activities that were critical in the development of state society. Isotopic evidence for animal captivity at Ceibal reveals that animal management played a greater role in Maya communities than previously believed.}, } @article {pmid29555749, year = {2018}, author = {Voogdt, CGP and Wagenaar, JA and van Putten, JPM}, title = {Duplicated TLR5 of zebrafish functions as a heterodimeric receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3221-E3229}, pmid = {29555749}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Animals ; Binding Sites ; Dimerization ; Flagellin/*metabolism ; *Gene Duplication ; HeLa Cells ; Humans ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Multimerization ; Sequence Homology ; Signal Transduction ; Toll-Like Receptor 5/*chemistry/genetics/*metabolism ; Zebrafish ; }, abstract = {Toll-like receptor 5 (TLR5) of mammals, birds, and reptiles detects bacterial flagellin and signals as a homodimeric complex. Structural studies using truncated TLR5b of zebrafish confirm the homodimeric TLR5-flagellin interaction. Here we provide evidence that zebrafish (Danio rerio) TLR5 unexpectedly signals as a heterodimer composed of the duplicated gene products drTLR5b and drTLR5a. Flagellin-induced signaling by the zebrafish TLR5 heterodimer increased in the presence of the TLR trafficking chaperone UNC93B1. Targeted exchange of drTLR5b and drTLR5a regions revealed that TLR5 activation needs a heterodimeric configuration of the receptor ectodomain and cytoplasmic domain, consistent with ligand-induced changes in receptor conformation. Structure-guided substitution of the presumed principal flagellin-binding site in human TLR5 with corresponding zebrafish TLR5 residues abrogated human TLR5 activation, indicating a species-specific TLR5-flagellin interaction. Our findings indicate that the duplicated TLR5 of zebrafish underwent subfunctionalization through concerted coevolution to form a unique heterodimeric flagellin receptor that operates fundamentally differently from TLR5 of other species.}, } @article {pmid29555748, year = {2018}, author = {}, title = {Correction for Callier, Inner Workings: How the butterfly got its spots (and why it matters).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3065}, doi = {10.1073/pnas.1803197115}, pmid = {29555748}, issn = {1091-6490}, } @article {pmid29555747, year = {2018}, author = {Storek, KM and Auerbach, MR and Shi, H and Garcia, NK and Sun, D and Nickerson, NN and Vij, R and Lin, Z and Chiang, N and Schneider, K and Wecksler, AT and Skippington, E and Nakamura, G and Seshasayee, D and Koerber, JT and Payandeh, J and Smith, PA and Rutherford, ST}, title = {Monoclonal antibody targeting the β-barrel assembly machine of Escherichia coli is bactericidal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3692-3697}, pmid = {29555747}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/*pharmacology ; Antibodies, Bacterial/*pharmacology ; Antibodies, Monoclonal/*pharmacology ; Bacterial Outer Membrane Proteins/*antagonists & inhibitors/immunology/metabolism ; Cell Membrane/drug effects/immunology/metabolism ; Escherichia coli/*drug effects/immunology/metabolism ; Escherichia coli Proteins/*antagonists & inhibitors/immunology/metabolism ; Membrane Fluidity/*drug effects ; Models, Molecular ; Protein Conformation ; Protein Folding ; }, abstract = {The folding and insertion of integral β-barrel membrane proteins into the outer membrane of Gram-negative bacteria is required for viability and bacterial pathogenesis. Unfortunately, the lack of selective and potent modulators to dissect β-barrel folding in vivo has hampered our understanding of this fundamental biological process. Here, we characterize a monoclonal antibody that selectively inhibits an essential component of the Escherichia coli β-barrel assembly machine, BamA. In the absence of complement or other immune factors, the unmodified antibody MAB1 demonstrates bactericidal activity against an E. coli strain with truncated LPS. Direct binding of MAB1 to an extracellular BamA epitope inhibits its β-barrel folding activity, induces periplasmic stress, disrupts outer membrane integrity, and kills bacteria. Notably, resistance to MAB1-mediated killing reveals a link between outer membrane fluidity and protein folding by BamA in vivo, underscoring the utility of this antibody for studying β-barrel membrane protein folding within a living cell. Identification of this BamA antagonist highlights the potential for new mechanisms of antibiotics to inhibit Gram-negative bacterial growth by targeting extracellular epitopes.}, } @article {pmid29555746, year = {2018}, author = {Liu, D and Stowie, A and de Zavalia, N and Leise, T and Pathak, SS and Drewes, LR and Davidson, AJ and Amir, S and Sonenberg, N and Cao, R}, title = {mTOR signaling in VIP neurons regulates circadian clock synchrony and olfaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3296-E3304}, pmid = {29555746}, issn = {1091-6490}, support = {SC1 GM112567/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; MOP7214//CIHR/Canada ; MOP142458//CIHR/Canada ; }, mesh = {Animals ; Circadian Rhythm/*physiology ; Mice ; Mice, Knockout ; Neurons/cytology/*physiology ; Olfactory Bulb/cytology/*physiology ; Olfactory Pathways ; Signal Transduction ; Suprachiasmatic Nucleus/cytology/*physiology ; TOR Serine-Threonine Kinases/*physiology ; Vasoactive Intestinal Peptide/*metabolism ; }, abstract = {Mammalian/mechanistic target of rapamycin (mTOR) signaling controls cell growth, proliferation, and metabolism in dividing cells. Less is known regarding its function in postmitotic neurons in the adult brain. Here we created a conditional mTOR knockout mouse model to address this question. Using the Cre-LoxP system, the mTOR gene was specifically knocked out in cells expressing Vip (vasoactive intestinal peptide), which represent a major population of interneurons widely distributed in the neocortex, suprachiasmatic nucleus (SCN), olfactory bulb (OB), and other brain regions. Using a combination of biochemical, behavioral, and imaging approaches, we found that mice lacking mTOR in VIP neurons displayed erratic circadian behavior and weakened synchronization among cells in the SCN, the master circadian pacemaker in mammals. Furthermore, we have discovered a critical role for mTOR signaling in mediating olfaction. Odor stimulated mTOR activation in the OB, anterior olfactory nucleus, as well as piriform cortex. Odor-evoked c-Fos responses along the olfactory pathway were abolished in mice lacking mTOR in VIP neurons, which is consistent with reduced olfactory sensitivity in these animals. Together, these results demonstrate that mTOR is a key regulator of SCN circadian clock synchrony and olfaction.}, } @article {pmid29555745, year = {2018}, author = {Pettigrew, MM and Ahearn, CP and Gent, JF and Kong, Y and Gallo, MC and Munro, JB and D'Mello, A and Sethi, S and Tettelin, H and Murphy, TF}, title = {Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3256-E3265}, pmid = {29555745}, issn = {1091-6490}, support = {R01 AI019641/AI/NIAID NIH HHS/United States ; UL1 TR001412/TR/NCATS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Amino Acid Sequence ; *Evolution, Molecular ; *Genome, Viral ; Haemophilus Infections/*epidemiology/virology ; Haemophilus influenzae/*genetics/isolation & purification ; Humans ; Mutation ; Phylogeny ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive/*complications ; Respiratory System/microbiology ; Viral Vaccines/*genetics/immunology ; Virulence/*genetics ; }, abstract = {Nontypeable Haemophilus influenzae (NTHi) exclusively colonize and infect humans and are critical to the pathogenesis of chronic obstructive pulmonary disease (COPD). In vitro and animal models do not accurately capture the complex environments encountered by NTHi during human infection. We conducted whole-genome sequencing of 269 longitudinally collected cleared and persistent NTHi from a 15-y prospective study of adults with COPD. Genome sequences were used to elucidate the phylogeny of NTHi isolates, identify genomic changes that occur with persistence in the human airways, and evaluate the effect of selective pressure on 12 candidate vaccine antigens. Strains persisted in individuals with COPD for as long as 1,422 d. Slipped-strand mispairing, mediated by changes in simple sequence repeats in multiple genes during persistence, regulates expression of critical virulence functions, including adherence, nutrient uptake, and modification of surface molecules, and is a major mechanism for survival in the hostile environment of the human airways. A subset of strains underwent a large 400-kb inversion during persistence. NTHi does not undergo significant gene gain or loss during persistence, in contrast to other persistent respiratory tract pathogens. Amino acid sequence changes occurred in 8 of 12 candidate vaccine antigens during persistence, an observation with important implications for vaccine development. These results indicate that NTHi alters its genome during persistence by regulation of critical virulence functions primarily by slipped-strand mispairing, advancing our understanding of how a bacterial pathogen that plays a critical role in COPD adapts to survival in the human respiratory tract.}, } @article {pmid29555744, year = {2018}, author = {Chen, X and DeAngelis, GC and Angelaki, DE}, title = {Flexible egocentric and allocentric representations of heading signals in parietal cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3305-E3312}, pmid = {29555744}, issn = {1091-6490}, support = {R01 DC014678/DC/NIDCD NIH HHS/United States ; R01 EY016178/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Eye Movements/*physiology ; Head Movements/*physiology ; Motion Perception/*physiology ; Neurons/*physiology ; Orientation ; Parietal Lobe/*physiology ; }, abstract = {By systematically manipulating head position relative to the body and eye position relative to the head, previous studies have shown that vestibular tuning curves of neurons in the ventral intraparietal (VIP) area remain invariant when expressed in body-/world-centered coordinates. However, body orientation relative to the world was not manipulated; thus, an egocentric, body-centered representation could not be distinguished from an allocentric, world-centered reference frame. We manipulated the orientation of the body relative to the world such that we could distinguish whether vestibular heading signals in VIP are organized in body- or world-centered reference frames. We found a hybrid representation, depending on gaze direction. When gaze remained fixed relative to the body, the vestibular heading tuning of VIP neurons shifted systematically with body orientation, indicating an egocentric, body-centered reference frame. In contrast, when gaze remained fixed relative to the world, this representation changed to be intermediate between body- and world-centered. We conclude that the neural representation of heading in posterior parietal cortex is flexible, depending on gaze and possibly attentional demands.}, } @article {pmid29555743, year = {2018}, author = {}, title = {Correction for Froidure et al., AtsPLA2-α nuclear relocalization by the Arabidopsis transcription factor AtMYB30 leads to repression of the plant defense response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3326-E3328}, doi = {10.1073/pnas.1803201115}, pmid = {29555743}, issn = {1091-6490}, } @article {pmid29555742, year = {2018}, author = {Chiu, CC and Keeling, CI and Bohlmann, J}, title = {Monoterpenyl esters in juvenile mountain pine beetle and sex-specific release of the aggregation pheromone trans-verbenol.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3652-3657}, pmid = {29555742}, issn = {1091-6490}, mesh = {Animals ; Coleoptera/drug effects/*physiology ; Esters/*pharmacology ; Female ; Male ; Monoterpenes/*metabolism/*pharmacology ; Pheromones/*metabolism ; Pinus/*chemistry ; Sesquiterpenes/*pharmacology ; Sexual Behavior/drug effects ; }, abstract = {A recent outbreak of mountain pine beetle (MPB) has spread over more than 25 million hectares of pine forests in western North America, affecting pine species of sensitive boreal and mountain ecosystems. During initial host colonization, female MPB produce and release the aggregation pheromone trans-verbenol to coordinate a mass attack of individual trees. trans-Verbenol is formed by hydroxylation of α-pinene, a monoterpene of the pine oleoresin defense. It is thought that adult females produce and immediately release trans-verbenol when encountering α-pinene on a new host tree. Here, we show that both sexes of MPB accumulate the monoterpenyl esters verbenyl oleate and verbenyl palmitate during their development in the brood tree. Verbenyl oleate and verbenyl palmitate were retained in adult female MPB until the time of emergence from brood trees, but were depleted in males. Adult females released trans-verbenol in response to treatment with juvenile hormone III (JHIII). While both sexes produced verbenyl esters when exposed to α-pinene, only females responded to JHIII with release of trans-verbenol. Accumulation of verbenyl esters at earlier life stages may allow adult females to release the aggregation pheromone trans-verbenol upon landing on a new host tree, independent of access to α-pinene. Formation of verbenyl esters may be part of a general detoxification system to overcome host monoterpene defenses in both sexes, from which a specialized and female-specific system of pheromone biosynthesis and release may have evolved.}, } @article {pmid29555741, year = {2018}, author = {}, title = {Correction for Gay-Antaki and Liverman, Climate for women in climate science: Women scientists and the Intergovernmental Panel on Climate Change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3324}, doi = {10.1073/pnas.1803793115}, pmid = {29555741}, issn = {1091-6490}, } @article {pmid29555740, year = {2018}, author = {Baird, D and Fairbairn, A and Jenkins, E and Martin, L and Middleton, C and Pearson, J and Asouti, E and Edwards, Y and Kabukcu, C and Mustafaoğlu, G and Russell, N and Bar-Yosef, O and Jacobsen, G and Wu, X and Baker, A and Elliott, S}, title = {Agricultural origins on the Anatolian plateau.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3077-E3086}, pmid = {29555740}, issn = {1091-6490}, mesh = {*Agriculture ; Animals ; *Archaeology ; *Farmers ; Goats ; Humans ; Middle East ; Sheep ; }, abstract = {This paper explores the explanations for, and consequences of, the early appearance of food production outside the Fertile Crescent of Southwest Asia, where it originated in the 10th/9th millennia cal BC. We present evidence that cultivation appeared in Central Anatolia through adoption by indigenous foragers in the mid ninth millennium cal BC, but also demonstrate that uptake was not uniform, and that some communities chose to actively disregard cultivation. Adoption of cultivation was accompanied by experimentation with sheep/goat herding in a system of low-level food production that was integrated into foraging practices rather than used to replace them. Furthermore, rather than being a short-lived transitional state, low-level food production formed part of a subsistence strategy that lasted for several centuries, although its adoption had significant long-term social consequences for the adopting community at Boncuklu. Material continuities suggest that Boncuklu's community was ancestral to that seen at the much larger settlement of Çatalhöyük East from 7100 cal BC, by which time a modest involvement with food production had been transformed into a major commitment to mixed farming, allowing the sustenance of a very large sedentary community. This evidence from Central Anatolia illustrates that polarized positions explaining the early spread of farming, opposing indigenous adoption to farmer colonization, are unsuited to understanding local sequences of subsistence and related social change. We go beyond identifying the mechanisms for the spread of farming by investigating the shorter- and longer-term implications of rejecting or adopting farming practices.}, } @article {pmid29555739, year = {2018}, author = {Wardrop, NA and Jochem, WC and Bird, TJ and Chamberlain, HR and Clarke, D and Kerr, D and Bengtsson, L and Juran, S and Seaman, V and Tatem, AJ}, title = {Spatially disaggregated population estimates in the absence of national population and housing census data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3529-3537}, pmid = {29555739}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 106866/Z/15/Z//Wellcome Trust/United Kingdom ; 204613/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {*Censuses ; Developing Countries ; Emigrants and Immigrants/*statistics & numerical data ; *Housing ; Humans ; *Models, Theoretical ; *Population Density ; *Population Dynamics ; }, abstract = {Population numbers at local levels are fundamental data for many applications, including the delivery and planning of services, election preparation, and response to disasters. In resource-poor settings, recent and reliable demographic data at subnational scales can often be lacking. National population and housing census data can be outdated, inaccurate, or missing key groups or areas, while registry data are generally lacking or incomplete. Moreover, at local scales accurate boundary data are often limited, and high rates of migration and urban growth make existing data quickly outdated. Here we review past and ongoing work aimed at producing spatially disaggregated local-scale population estimates, and discuss how new technologies are now enabling robust and cost-effective solutions. Recent advances in the availability of detailed satellite imagery, geopositioning tools for field surveys, statistical methods, and computational power are enabling the development and application of approaches that can estimate population distributions at fine spatial scales across entire countries in the absence of census data. We outline the potential of such approaches as well as their limitations, emphasizing the political and operational hurdles for acceptance and sustainable implementation of new approaches, and the continued importance of traditional sources of national statistical data.}, } @article {pmid29555738, year = {2018}, author = {Niedringhaus, A and Policht, VR and Sechrist, R and Konar, A and Laible, PD and Bocian, DF and Holten, D and Kirmaier, C and Ogilvie, JP}, title = {Primary processes in the bacterial reaction center probed by two-dimensional electronic spectroscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3563-3568}, pmid = {29555738}, issn = {1091-6490}, mesh = {*Electrons ; Kinetics ; *Models, Biological ; Photosynthesis ; Photosynthetic Reaction Center Complex Proteins/*chemistry/*metabolism ; Rhodobacter sphaeroides/*metabolism ; Spectrum Analysis/*methods ; }, abstract = {In the initial steps of photosynthesis, reaction centers convert solar energy to stable charge-separated states with near-unity quantum efficiency. The reaction center from purple bacteria remains an important model system for probing the structure-function relationship and understanding mechanisms of photosynthetic charge separation. Here we perform 2D electronic spectroscopy (2DES) on bacterial reaction centers (BRCs) from two mutants of the purple bacterium Rhodobacter capsulatus, spanning the Q y absorption bands of the BRC. We analyze the 2DES data using a multiexcitation global-fitting approach that employs a common set of basis spectra for all excitation frequencies, incorporating inputs from the linear absorption spectrum and the BRC structure. We extract the exciton energies, resolving the previously hidden upper exciton state of the special pair. We show that the time-dependent 2DES data are well-represented by a two-step sequential reaction scheme in which charge separation proceeds from the excited state of the special pair (P*) to P+HA- via the intermediate P+BA- When inhomogeneous broadening and Stark shifts of the B* band are taken into account we can adequately describe the 2DES data without the need to introduce a second charge-separation pathway originating from the excited state of the monomeric bacteriochlorophyll BA*.}, } @article {pmid29555737, year = {2018}, author = {}, title = {Correction for Place et al., MicroRNA-373 induces expression of genes with complementary promoter sequences.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3325}, doi = {10.1073/pnas.1803343115}, pmid = {29555737}, issn = {1091-6490}, } @article {pmid29555736, year = {2018}, author = {Ardevol, A and Hummer, G}, title = {Retinal isomerization and water-pore formation in channelrhodopsin-2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3557-3562}, pmid = {29555736}, issn = {1091-6490}, mesh = {Channelrhodopsins/*chemistry/*metabolism ; Chlamydomonas reinhardtii/*metabolism ; Hydrogen Bonding ; Isomerism ; Light ; Models, Molecular ; Protein Conformation ; Retinaldehyde/*chemistry/*metabolism ; Water/chemistry/*metabolism ; }, abstract = {Channelrhodopsin-2 (ChR2) is a light-sensitive ion channel widely used in optogenetics. Photoactivation triggers a trans-to-cis isomerization of a covalently bound retinal. Ensuing conformational changes open a cation-selective channel. We explore the structural dynamics in the early photocycle leading to channel opening by classical (MM) and quantum mechanical (QM) molecular simulations. With QM/MM simulations, we generated a protein-adapted force field for the retinal chromophore, which we validated against absorption spectra. In a 4-µs MM simulation of a dark-adapted ChR2 dimer, water entered the vestibules of the closed channel. Retinal all-trans to 13-cis isomerization, simulated with metadynamics, triggered a major restructuring of the charge cluster forming the channel gate. On a microsecond time scale, water penetrated the gate to form a membrane-spanning preopen pore between helices H1, H2, H3, and H7. This influx of water into an ion-impermeable preopen pore is consistent with time-resolved infrared spectroscopy and electrophysiology experiments. In the retinal 13-cis state, D253 emerged as the proton acceptor of the Schiff base. Upon proton transfer from the Schiff base to D253, modeled by QM/MM simulations, we obtained an early-M/P2390-like intermediate. Rapid rotation of the unprotonated Schiff base toward the cytosolic side effectively prevents its reprotonation from the extracellular side. From MM and QM simulations, we gained detailed insight into the mechanism of ChR2 photoactivation and early events in pore formation. By rearranging the network of charges and hydrogen bonds forming the gate, water emerges as a key player in light-driven ChR2 channel opening.}, } @article {pmid29555735, year = {2018}, author = {}, title = {Correction for Lu et al., High-order above-threshold dissociation of molecules.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3323}, doi = {10.1073/pnas.1803614115}, pmid = {29555735}, issn = {1091-6490}, } @article {pmid29555734, year = {2018}, author = {Bechtel, MM and Liesch, R and Scheve, KF}, title = {Inequality and redistribution behavior in a give-or-take game.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3611-3616}, pmid = {29555734}, issn = {1091-6490}, mesh = {*Continental Population Groups ; *Games, Experimental ; Humans ; *Income ; *Social Class ; *Socioeconomic Factors ; }, abstract = {Political polarization and extremism are widely thought to be driven by the surge in economic inequality in many countries around the world. Understanding why inequality persists depends on knowing the causal effect of inequality on individual behavior. We study how inequality affects redistribution behavior in a randomized "give-or-take" experiment that created equality, advantageous inequality, or disadvantageous inequality between two individuals before offering one of them the opportunity to either take from or give to the other. We estimate the causal effect of inequality in representative samples of German and American citizens (n = 4,966) and establish two main findings. First, individuals imperfectly equalize payoffs: On average, respondents transfer 12% of the available endowments to realize more equal wealth distributions. This means that respondents tolerate a considerable degree of inequality even in a setting in which there are no costs to redistribution. Second, redistribution behavior in response to disadvantageous and advantageous inequality is largely asymmetric: Individuals who take from those who are richer do not also tend to give to those who are poorer, and individuals who give to those who are poorer do not tend to take from those who are richer. These behavioral redistribution types correlate in meaningful ways with support for heavy taxes on the rich and the provision of welfare benefits for the poor. Consequently, it seems difficult to construct a majority coalition willing to back the type of government interventions needed to counter rising inequality.}, } @article {pmid29555733, year = {2018}, author = {Nowakowski, AJ and Frishkoff, LO and Thompson, ME and Smith, TM and Todd, BD}, title = {Phylogenetic homogenization of amphibian assemblages in human-altered habitats across the globe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3454-E3462}, pmid = {29555733}, issn = {1091-6490}, mesh = {Amphibians/*classification/genetics ; Animals ; Biodiversity ; Biological Evolution ; *Ecosystem ; Humans ; *Phylogeny ; }, abstract = {Habitat conversion is driving biodiversity loss and restructuring species assemblages across the globe. Responses to habitat conversion vary widely, however, and little is known about the degree to which shared evolutionary history underlies changes in species richness and composition. We analyzed data from 48 studies, comprising 438 species on five continents, to understand how taxonomic and phylogenetic diversity of amphibian assemblages shifts in response to habitat conversion. We found that evolutionary history explains the majority of variation in species' responses to habitat conversion, with specific clades scattered across the amphibian tree of life being favored by human land uses. Habitat conversion led to an average loss of 139 million years of amphibian evolutionary history within assemblages, high species and lineage turnover at landscape scales, and phylogenetic homogenization at the global scale (despite minimal taxonomic homogenization). Lineage turnover across habitats was greatest in lowland tropical regions where large species pools and stable climates have perhaps given rise to many microclimatically specialized species. Together, our results indicate that strong phylogenetic clustering of species' responses to habitat conversion mediates nonrandom structuring of local assemblages and loss of global phylogenetic diversity. In an age of rapid global change, identifying clades that are most sensitive to habitat conversion will help prioritize use of limited conservation resources.}, } @article {pmid29555732, year = {2018}, author = {Zaks, MA and Nepomnyashchy, A}, title = {Subdiffusive and superdiffusive transport in plane steady viscous flows.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1717225115}, pmid = {29555732}, issn = {1091-6490}, abstract = {Deterministic transport of passive tracers in steady laminar plane flows of incompressible viscous fluids through lattices of solid bodies or arrays of steady vortices can be anomalous. Motion along regular patterns of streamlines is often aperiodic: Repeated slow passages near stagnation points and/or solid surfaces serve for eventual decorrelation. Singularities of passage times near the obstacles, dictated by the boundary conditions, affect the character of transport anomalies: Flows past arrays of vortices are subdiffusive whereas tracers advected through lattices of solid obstacles can feature superdiffusion. We calculate the transport characteristics with the help of the simple and computationally efficient model: the special flow.}, } @article {pmid29555731, year = {2018}, author = {Stevenson, TC and Cywes-Bentley, C and Moeller, TD and Weyant, KB and Putnam, D and Chang, YF and Jones, BD and Pier, GB and DeLisa, MP}, title = {Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3106-E3115}, pmid = {29555731}, issn = {1091-6490}, support = {R21 EB005669/EB/NIBIB NIH HHS/United States ; R44 GM088905/GM/NIGMS NIH HHS/United States ; U54 AI057160/AI/NIAID NIH HHS/United States ; P01 AI044642/AI/NIAID NIH HHS/United States ; R01 EY016144/EY/NEI NIH HHS/United States ; R43 GM088905/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Bacterial/*immunology ; Antigens, Surface/*immunology ; Bacteria/*immunology ; Bacterial Infections/immunology/*prevention & control ; Bacterial Vaccines/immunology/*therapeutic use ; Female ; Immunization/*methods ; Mice ; Mice, Inbred BALB C ; Transport Vesicles/*immunology ; Vaccines, Conjugate/immunology/therapeutic use ; beta-Glucans/metabolism ; }, abstract = {Many microbial pathogens produce a β-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule, including bacterial, fungal, and protozoan cells. Broadly protective immune responses to this single conserved polysaccharide antigen in animals are possible but only when a deacetylated poly-N-acetyl-d-glucosamine (dPNAG; <30% acetate) glycoform is administered as a conjugate to a carrier protein. Unfortunately, conventional methods for natural extraction or chemical synthesis of dPNAG and its subsequent conjugation to protein carriers can be technically demanding and expensive. Here, we describe an alternative strategy for creating broadly protective vaccine candidates that involved coordinating recombinant poly-N-acetyl-d-glucosamine (rPNAG) biosynthesis with outer membrane vesicle (OMV) formation in laboratory strains of Escherichia coli The glycosylated outer membrane vesicles (glycOMVs) released by these engineered bacteria were decorated with the PNAG glycopolymer and induced high titers of PNAG-specific IgG antibodies after immunization in mice. When a Staphylococcus aureus enzyme responsible for PNAG deacetylation was additionally expressed in these cells, glycOMVs were generated that elicited antibodies to both highly acetylated PNAG (∼95-100% acetate) and a chemically deacetylated dPNAG derivative (∼15% acetate). These antibodies mediated efficient in vitro killing of two distinct PNAG-positive bacterial species, namely S. aureus and Francisella tularensis subsp. holarctica, and mice immunized with PNAG-containing glycOMVs developed protective immunity against these unrelated pathogens. Collectively, our results reveal the potential of glycOMVs for targeting this conserved polysaccharide antigen and engendering protective immunity against the broad range of pathogens that produce surface PNAG.}, } @article {pmid29555730, year = {2018}, author = {Gonzalez, KL and Ratzel, SE and Burks, KH and Danan, CH and Wages, JM and Zolman, BK and Bartel, B}, title = {A pex1 missense mutation improves peroxisome function in a subset of Arabidopsis pex6 mutants without restoring PEX5 recycling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3163-E3172}, pmid = {29555730}, issn = {1091-6490}, support = {R01 GM079177/GM/NIGMS NIH HHS/United States ; UL1 RR024992/RR/NCRR NIH HHS/United States ; S10 RR026399/RR/NCRR NIH HHS/United States ; P30 CA091842/CA/NCI NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {ATPases Associated with Diverse Cellular Activities/*genetics/metabolism ; Arabidopsis/growth & development/*metabolism ; Arabidopsis Proteins/*genetics/*metabolism ; Autophagy ; Membrane Proteins/*genetics/metabolism ; *Mutation, Missense ; Peroxisome-Targeting Signal 1 Receptor/*metabolism ; Peroxisomes/*physiology ; Protein Transport ; Ubiquitination ; }, abstract = {Peroxisomes are eukaryotic organelles critical for plant and human development because they house essential metabolic functions, such as fatty acid β-oxidation. The interacting ATPases PEX1 and PEX6 contribute to peroxisome function by recycling PEX5, a cytosolic receptor needed to import proteins targeted to the peroxisomal matrix. Arabidopsis pex6 mutants exhibit low PEX5 levels and defects in peroxisomal matrix protein import, oil body utilization, peroxisomal metabolism, and seedling growth. These defects are hypothesized to stem from impaired PEX5 retrotranslocation leading to PEX5 polyubiquitination and consequent degradation of PEX5 via the proteasome or of the entire organelle via autophagy. We recovered a pex1 missense mutation in a screen for second-site suppressors that restore growth to the pex6-1 mutant. Surprisingly, this pex1-1 mutation ameliorated the metabolic and physiological defects of pex6-1 without restoring PEX5 levels. Similarly, preventing autophagy by introducing an atg7-null allele partially rescued pex6-1 physiological defects without restoring PEX5 levels. atg7 synergistically improved matrix protein import in pex1-1 pex6-1, implying that pex1-1 improves peroxisome function in pex6-1 without impeding autophagy of peroxisomes (i.e., pexophagy). pex1-1 differentially improved peroxisome function in various pex6 alleles but worsened the physiological and molecular defects of a pex26 mutant, which is defective in the tether anchoring the PEX1-PEX6 hexamer to the peroxisome. Our results support the hypothesis that, beyond PEX5 recycling, PEX1 and PEX6 have additional functions in peroxisome homeostasis and perhaps in oil body utilization.}, } @article {pmid29555296, year = {2018}, author = {Grummer, JA and Morando, MM and Avila, LJ and Sites, JW and Leaché, AD}, title = {Phylogenomic evidence for a recent and rapid radiation of lizards in the Patagonian Liolaemus fitzingerii species group.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {243-254}, doi = {10.1016/j.ympev.2018.03.023}, pmid = {29555296}, issn = {1095-9513}, support = {S10 OD018174/OD/NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; DNA, Mitochondrial/genetics ; *Genomics ; Geography ; Hybridization, Genetic ; Lizards/*genetics ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Rapid evolutionary radiations are difficult to resolve because divergence events are nearly synchronous and gene flow among nascent species can be high, resulting in a phylogenetic "bush". Large datasets composed of sequence loci from across the genome can potentially help resolve some of these difficult phylogenetic problems. A suitable test case is the Liolaemus fitzingerii species group of lizards, which includes twelve species that are broadly distributed in Argentinean Patagonia. The species in the group have had a complex evolutionary history that has led to high morphological variation and unstable taxonomy. We generated a sequence capture dataset for 28 ingroup individuals of 580 nuclear loci, alongside a mitogenomic dataset, to infer phylogenetic relationships among species in this group. Relationships among species were generally weakly supported with the nuclear data, and along with an inferred age of ∼2.6 million years old, indicate either rapid evolution, hybridization, incomplete lineage sorting, non-informative data, or a combination thereof. We inferred a signal of mito-nuclear discordance, indicating potential hybridization between L. melanops and L. martorii, and phylogenetic network analyses provided support for 5 reticulation events among species. Phasing the nuclear loci did not provide additional insight into relationships or suspected patterns of hybridization. Only one clade, composed of L. camarones, L. fitzingerii, and L. xanthoviridis was recovered across all analyses. Genomic datasets provide molecular systematists with new opportunities to resolve difficult phylogenetic problems, yet the lack of phylogenetic resolution in Patagonian Liolaemus is biologically meaningful and indicative of a recent and rapid evolutionary radiation. The phylogenetic relationships of the Liolaemus fitzingerii group may be best modeled as a reticulated network instead of a bifurcating phylogeny.}, } @article {pmid29555295, year = {2018}, author = {Kotsakiozi, P and Jablonski, D and Ilgaz, Ç and Kumlutaş, Y and Avcı, A and Meiri, S and Itescu, Y and Kukushkin, O and Gvoždík, V and Scillitani, G and Roussos, SA and Jandzik, D and Kasapidis, P and Lymberakis, P and Poulakakis, N}, title = {Multilocus phylogeny and coalescent species delimitation in Kotschy's gecko, Mediodactylus kotschyi: Hidden diversity and cryptic species.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {177-187}, doi = {10.1016/j.ympev.2018.03.022}, pmid = {29555295}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; *Genetic Loci ; *Genetic Variation ; Geography ; Lizards/*classification/*genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Alignment ; Species Specificity ; Time Factors ; }, abstract = {Kotschy's Gecko, Mediodactylus kotschyi, is a small gecko native to southeastern Europe and the Levant. It displays great morphological variation with a large number of morphologically recognized subspecies. However, it has been suggested that it constitutes a species complex of several yet unrecognized species. In this study, we used multilocus sequence data (three mitochondrial and three nuclear gene fragments) to estimate the phylogenetic relationships of 174 specimens from 129 sampling localities, covering a substantial part of the distribution range of the species. Our results revealed high genetic diversity of M. kotschyi populations and contributed to our knowledge about the phylogenetic relationships and the estimation of the divergence times between them. Diversification within M. kotschyi began approximately 15 million years ago (Mya) in the Middle Miocene, whereas the diversification within most of the major clades have been occurred in the last 5 Mya. Species delimitation analysis suggests there exists five species within the complex, and we propose to tentatively recognize the following taxa as full species: M. kotschyi (mainland Balkans, most of Aegean islands, and Italy), M. orientalis (Levant, Cyprus, southern Anatolia, and south-eastern Aegean islands), M. danilewskii (Black Sea region and south-western Anatolia), M. bartoni (Crete), and M. oertzeni (southern Dodecanese Islands). This newly recognized diversity underlines the complex biogeographical history of the Eastern Mediterranean region.}, } @article {pmid29555294, year = {2018}, author = {Bryson, RW and Zarza, E and Grummer, JA and Parra-Olea, G and Flores-Villela, O and Klicka, J and McCormack, JE}, title = {Phylogenomic insights into the diversification of salamanders in the Isthmura bellii group across the Mexican highlands.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {78-84}, doi = {10.1016/j.ympev.2018.03.024}, pmid = {29555294}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Calibration ; *Ecosystem ; Mexico ; *Phylogeny ; Phylogeography ; Time Factors ; Urodela/*classification/*genetics ; }, abstract = {Mountain formation in Mexico has played an important role in the diversification of many Mexican taxa. The Trans-Mexican Volcanic Belt in particular has served as both a cradle of diversification and conduit for dispersal. We investigated the evolutionary history of the Isthmura bellii group of salamanders, a widespread amphibian across the Mexican highlands, using sequence capture of ultraconserved elements. Results suggest that the I. bellii group probably originated in southeastern Mexico in the late Miocene and later dispersed across the Trans-Mexican Volcanic Belt and into the Sierra Madre Occidental. Pre-Pleistocene uplift of the Trans-Volcanic Belt likely promoted early diversification by serving as a mesic land-bridge across central Mexico. These findings highlight the importance of the Trans-Volcanic Belt in generating Mexico's rich biodiversity.}, } @article {pmid29555242, year = {2018}, author = {Sepúlveda-Ramírez, SP and Toledo-Jacobo, L and Henson, JH and Shuster, CB}, title = {Cdc42 controls primary mesenchyme cell morphogenesis in the sea urchin embryo.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {140-151}, pmid = {29555242}, issn = {1095-564X}, support = {R15 HD080533/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Culture Techniques ; Cell Movement/genetics ; Embryo, Nonmammalian/metabolism ; Gene Expression Regulation, Developmental ; Mesoderm/cytology/*metabolism ; Morphogenesis/*genetics ; Real-Time Polymerase Chain Reaction ; Sea Urchins ; cdc42 GTP-Binding Protein/*metabolism ; }, abstract = {In the sea urchin embryo, gastrulation is characterized by the ingression and directed cell migration of primary mesenchyme cells (PMCs), as well as the primary invagination and convergent extension of the endomesoderm. Like all cell shape changes, individual and collective cell motility is orchestrated by Rho family GTPases and their modulation of the actomyosin cytoskeleton. And while endomesoderm specification has been intensively studied in echinoids, much less is known about the proximate regulators driving cell motility. Toward these ends, we employed anti-sense morpholinos, mutant alleles and pharmacological inhibitors to assess the role of Cdc42 during sea urchin gastrulation. While inhibition of Cdc42 expression or activity had only mild effects on PMC ingression, PMC migration, alignment and skeletogenesis were disrupted in the absence of Cdc42, as well as elongation of the archenteron. PMC migration and patterning of the larval skeleton relies on the extension of filopodia, and Cdc42 was required for filopodia in vivo as well as in cultured PMCs. Lastly, filopodial extension required both Arp2/3 and formin actin-nucleating factors, supporting models of filopodial nucleation observed in other systems. Together, these results suggest that Cdc42 plays essential roles during PMC cell motility and organogenesis.}, } @article {pmid29555241, year = {2018}, author = {Klaassen, H and Wang, Y and Adamski, K and Rohner, N and Kowalko, JE}, title = {CRISPR mutagenesis confirms the role of oca2 in melanin pigmentation in Astyanax mexicanus.}, journal = {Developmental biology}, volume = {441}, number = {2}, pages = {313-318}, doi = {10.1016/j.ydbio.2018.03.014}, pmid = {29555241}, issn = {1095-564X}, mesh = {Albinism/genetics/metabolism ; Animals ; *CRISPR-Cas Systems ; Characiformes/*genetics/metabolism ; Fish Proteins/*genetics/metabolism ; *Gene Editing ; Melatonin/biosynthesis/*genetics ; Membrane Transport Proteins/*genetics/metabolism ; Pigmentation/*genetics ; }, abstract = {Understanding the genetic basis of trait evolution is critical to identifying the mechanisms that generated the immense amount of diversity observable in the living world. However, genetically manipulating organisms from natural populations with evolutionary adaptations remains a significant challenge. Astyanax mexicanus exists in two interfertile forms, a surface-dwelling form and multiple independently evolved cave-dwelling forms. Cavefish have evolved a number of morphological and behavioral traits and multiple quantitative trait loci (QTL) analyses have been performed to identify loci underlying these traits. These studies provide a unique opportunity to identify and test candidate genes for these cave-specific traits. We have leveraged the CRISPR/Cas9 genome editing techniques to characterize the effects of mutations in oculocutaneous albinism II (oca2), a candidate gene hypothesized to be responsible for the evolution of albinism in A. mexicanus cave populations. We generated oca2 mutant surface A. mexicanus. Surface fish with oca2 mutations are albino due to a disruption in the first step of the melanin synthesis pathway, the same step that is disrupted in albino cavefish. Hybrid offspring from crosses between oca2 mutant surface and cavefish are albino, definitively demonstrating the role of this gene in the evolution of albinism in this species. This research elucidates the role oca2 plays in pigmentation in fish, and establishes that this gene is solely responsible for the evolution of albinism in multiple cavefish populations. Finally, it demonstrates the utility of using genome editing to investigate the genetic basis of trait evolution.}, } @article {pmid29555198, year = {2018}, author = {Bentivoglio, M and Bertini, G}, title = {Alive and Ticking: Trypanosoma brucei Assaults the Circadian Clocks.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {265-267}, doi = {10.1016/j.pt.2018.03.003}, pmid = {29555198}, issn = {1471-5007}, mesh = {Animals ; Circadian Clocks ; Circadian Rhythm ; Humans ; Mice ; Trypanosoma ; *Trypanosoma brucei brucei ; *Trypanosomiasis, African ; }, abstract = {Rijo-Ferreira et al. report alterations of circadian rhythmicity at the behavioral, tissue, cellular, and molecular levels in mice after Trypanosoma brucei infection, showing that targeting cell clocks is a specific feature of these parasites. Thus, African trypanosomes cause a severe disease by disrupting time-keeping mechanisms and their synchrony.}, } @article {pmid29554982, year = {2018}, author = {Young, E and Carey, M and Meharg, AA and Meharg, C}, title = {Microbiome and ecotypic adaption of Holcus lanatus (L.) to extremes of its soil pH range, investigated through transcriptome sequencing.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {48}, pmid = {29554982}, issn = {2049-2618}, mesh = {Adaptation, Physiological/*physiology ; Ascomycota/genetics/*growth & development ; Colletotrichum/genetics/growth & development ; Fusarium/genetics/growth & development ; Holcus/growth & development/*microbiology ; Microbiota/*genetics ; Mycorrhizae/physiology ; Oomycetes/genetics/*growth & development ; Plant Roots/*microbiology ; Soil/chemistry ; Soil Microbiology ; Symbiosis/*physiology ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Plants can adapt to edaphic stress, such as nutrient deficiency, toxicity and biotic challenges, by controlled transcriptomic responses, including microbiome interactions. Traditionally studied in model plant species with controlled microbiota inoculation treatments, molecular plant-microbiome interactions can be functionally investigated via RNA-Seq. Complex, natural plant-microbiome studies are limited, typically focusing on microbial rRNA and omitting functional microbiome investigations, presenting a fundamental knowledge gap. Here, root and shoot meta-transcriptome analyses, in tandem with shoot elemental content and root staining, were employed to investigate transcriptome responses in the wild grass Holcus lanatus and its associated natural multi-species eukaryotic microbiome. A full factorial reciprocal soil transplant experiment was employed, using plant ecotypes from two widely contrasting natural habitats, acid bog and limestone quarry soil, to investigate naturally occurring, and ecologically meaningful, edaphically driven molecular plant-microbiome interactions.

RESULTS: Arbuscular mycorrhizal (AM) and non-AM fungal colonization was detected in roots in both soils. Staining showed greater levels of non-AM fungi, and transcriptomics indicated a predominance of Ascomycota-annotated genes. Roots in acid bog soil were dominated by Phialocephala-annotated transcripts, a putative growth-promoting endophyte, potentially involved in N nutrition and ion homeostasis. Limestone roots in acid bog soil had greater expression of other Ascomycete genera and Oomycetes and lower expression of Phialocephala-annotated transcripts compared to acid ecotype roots, which corresponded with reduced induction of pathogen defense processes, particularly lignin biosynthesis in limestone ecotypes. Ascomycota dominated in shoots and limestone soil roots, but Phialocephala-annotated transcripts were insignificant, and no single Ascomycete genus dominated. Fusarium-annotated transcripts were the most common genus in shoots, with Colletotrichum and Rhizophagus (AM fungi) most numerous in limestone soil roots. The latter coincided with upregulation of plant genes involved in AM symbiosis initiation and AM-based P acquisition in an environment where P availability is low.

CONCLUSIONS: Meta-transcriptome analyses provided novel insights into H. lanatus transcriptome responses, associated eukaryotic microbiota functions and taxonomic community composition. Significant edaphic and plant ecotype effects were identified, demonstrating that meta-transcriptome-based functional analysis is a powerful tool for the study of natural plant-microbiome interactions.}, } @article {pmid29554976, year = {2018}, author = {Lee, TY and Wang, CW and Chen, TW and Chan, DC and Liao, GS and Fan, HL}, title = {Ovarian metastases from gallbladder mimics primary ovarian neoplasm in young patient: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {185}, pmid = {29554976}, issn = {1756-0500}, mesh = {Adult ; Diagnosis, Differential ; Female ; Gallbladder/*pathology ; Gallbladder Neoplasms/diagnosis/*pathology ; Humans ; Ovarian Neoplasms/diagnosis/*secondary ; Ovary/*pathology ; }, abstract = {BACKGROUND: Gallbladder cancer is unusually seen but can result in highly mortality rate. It makes challenge to diagnose for clinicians due to present asymptomatic or non-specific clinical presentation including abdominal pain, anorexia. It usually also accompanies with cholelithiasis (incidence is 1-2%) and incidentally detected by radiologic examination such as ultrasound, computed tomography or intra-operative intervention accidentally. Gallbladder cancer results in highly fatal malignancy because it is difficult to early detect. The ovarian metastases from gallbladder mimics primary neoplasm isn't seen before and mentioned in English literatures before.

CASE PRESENTATION: A 28-year-old woman suffered from intermittently lower abdominal tenderness and nausea after meals for 3 years. The abdominal ultrasound revealed a right ovarian mass with fluid accumulation and the contrast CT of abdomen revealed a gallbladder fundus mass and liver tumor lesion located at segment 4. We arranged surgical intervention with radical cholecystectomy and debulking operation with salpingo-oophorectomy. The pathologic report revealed adenocarcinoma of gallbladder with liver, peritoneum, and right ovarian invasion. After surgical intervention, she also received adjuvant chemotherapy with Gemcitabine, Cetuximab, Cisplatin and Cyberknife.

CONCLUSION: The non-specific symptoms make the challenge to difference the primary malignant neoplasm. The rarely diagnosis must take in consider if the gastrointestinal tract tumours coexist with ovarian tumours.}, } @article {pmid29554952, year = {2018}, author = {Dulla, O and Sultana, S and Shohag Hosen, M}, title = {In vitro comparative quality evaluation of different brands of esomeprazole tablets available in selected community pharmacies in Dhaka, Bangladesh.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {184}, pmid = {29554952}, issn = {1756-0500}, mesh = {Bangladesh ; Chemistry, Pharmaceutical/methods ; Esomeprazole/*analysis/chemistry/standards ; Humans ; Pharmacies/standards/*statistics & numerical data ; Proton Pump Inhibitors/analysis/chemistry/standards ; Quality Control ; Tablets, Enteric-Coated/*analysis/chemistry/standards ; Total Quality Management/*methods ; }, abstract = {OBJECTIVE: Esomeprazole is the S-isomer of omeprazole, used to treat gastro esophageal reflux disease. It is one of the widely manufactured and marketed drugs by many pharmaceutical companies in Bangladesh. The aim of the study is to compare the different physical parameters including hardness, friability, diameter, thickness, disintegration time, dissolution test and assay for quality evaluation and characterization of tablets of five different brands of Bangladeshi pharmaceutical company. The specified compendial method was followed for their evaluation test.

RESULTS: Esomeprazole Mg tablets are enteric coated tablet, there was no disintegration for any brand occurred in 0.1 N HCl after 2 h and all tablets were disintegrated within 19.93 ± 0.04 to 29.05 ± 0.14 min in phosphate buffer (pH 6.8). Weight variation and Hardness were between 1.01 ± 0.29 to 2.01 ± 0.14% and 5.32 ± 0.06 to 7.12 ± 0.12 kgf respectively. Medicine released after 2 h in 0.1 N HCl were varied from 2.55 ± 0.24 to 4.47 ± 0.31% which was less than 10% and in phosphate buffer (pH 6.8) the percentage of medicine release were between 100.9 and 105.9% after 60 min. In case of assay the results of all brands were between 95.28 ± 0.08 and 99.40 ± 0.11%. The obtained results of all parameters were complied with pharmacopoeial limit. So from this study we can conclude that products of esomeprazole available in Bangladeshi pharmaceutical market meet the quality parameter to satisfy therapeutic efficacy.}, } @article {pmid29554951, year = {2018}, author = {Guégan, M and Zouache, K and Démichel, C and Minard, G and Tran Van, V and Potier, P and Mavingui, P and Valiente Moro, C}, title = {The mosquito holobiont: fresh insight into mosquito-microbiota interactions.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {49}, pmid = {29554951}, issn = {2049-2618}, mesh = {Animals ; Bacteria/*metabolism ; Culicidae/*microbiology ; Host-Pathogen Interactions/*physiology ; Microbiota/*physiology ; Mosquito Vectors/*microbiology ; Symbiosis/*physiology ; }, abstract = {The holobiont concept was first developed for coral ecosystems but has been extended to multiple organisms, including plants and other animals. Studies on insect-associated microbial communities have produced strong evidence that symbiotic bacteria play a major role in host biology. However, the understanding of these symbiotic relationships has mainly been limited to phytophagous insects, while the role of host-associated microbiota in haematophagous insect vectors remains largely unexplored. Mosquitoes are a major global public health concern, with a concomitant increase in people at risk of infection. The global emergence and re-emergence of mosquito-borne diseases has led many researchers to study both the mosquito host and its associated microbiota. Although most of these studies have been descriptive, they have led to a broad description of the bacterial communities hosted by mosquito populations. This review describes key advances and progress in the field of the mosquito microbiota research while also encompassing other microbes and the environmental factors driving their composition and diversity. The discussion includes recent findings on the microbiota functional roles and underlines their interactions with the host biology and pathogen transmission. Insight into the ecology of multipartite interactions, we consider that conferring the term holobiont to the mosquito and its microbiota is useful to get a comprehensive understanding of the vector pathosystem functioning so as to be able to develop innovative and efficient novel vector control strategies.}, } @article {pmid29554948, year = {2018}, author = {Walsh, AM and Crispie, F and O'Sullivan, O and Finnegan, L and Claesson, MJ and Cotter, PD}, title = {Species classifier choice is a key consideration when analysing low-complexity food microbiome data.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {50}, pmid = {29554948}, issn = {2049-2618}, support = {SFI/12/RC/2273//Science Foundation Ireland/Ireland ; 11/PI/1137//Science Foundation Ireland/Ireland ; 13/SIRG/2160//Science Foundation Ireland/Ireland ; }, mesh = {Bacteria/classification/*genetics ; Base Sequence/genetics ; Computational Biology/methods ; DNA, Bacterial/*genetics ; Food Microbiology/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Metagenome/genetics ; Metagenomics/*methods ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The use of shotgun metagenomics to analyse low-complexity microbial communities in foods has the potential to be of considerable fundamental and applied value. However, there is currently no consensus with respect to choice of species classification tool, platform, or sequencing depth. Here, we benchmarked the performances of three high-throughput short-read sequencing platforms, the Illumina MiSeq, NextSeq 500, and Ion Proton, for shotgun metagenomics of food microbiota. Briefly, we sequenced six kefir DNA samples and a mock community DNA sample, the latter constructed by evenly mixing genomic DNA from 13 food-related bacterial species. A variety of bioinformatic tools were used to analyse the data generated, and the effects of sequencing depth on these analyses were tested by randomly subsampling reads.

RESULTS: Compositional analysis results were consistent between the platforms at divergent sequencing depths. However, we observed pronounced differences in the predictions from species classification tools. Indeed, PERMANOVA indicated that there was no significant differences between the compositional results generated by the different sequencers (p = 0.693, R2 = 0.011), but there was a significant difference between the results predicted by the species classifiers (p = 0.01, R2 = 0.127). The relative abundances predicted by the classifiers, apart from MetaPhlAn2, were apparently biased by reference genome sizes. Additionally, we observed varying false-positive rates among the classifiers. MetaPhlAn2 had the lowest false-positive rate, whereas SLIMM had the greatest false-positive rate. Strain-level analysis results were also similar across platforms. Each platform correctly identified the strains present in the mock community, but accuracy was improved slightly with greater sequencing depth. Notably, PanPhlAn detected the dominant strains in each kefir sample above 500,000 reads per sample. Again, the outputs from functional profiling analysis using SUPER-FOCUS were generally accordant between the platforms at different sequencing depths. Finally, and expectedly, metagenome assembly completeness was significantly lower on the MiSeq than either on the NextSeq (p = 0.03) or the Proton (p = 0.011), and it improved with increased sequencing depth.

CONCLUSIONS: Our results demonstrate a remarkable similarity in the results generated by the three sequencing platforms at different sequencing depths, and, in fact, the choice of bioinformatics methodology had a more evident impact on results than the choice of sequencer did.}, } @article {pmid29554913, year = {2018}, author = {Zhu, Y and Zhang, F and Huang, Z}, title = {Structural insights into the inactivation of CRISPR-Cas systems by diverse anti-CRISPR proteins.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {32}, pmid = {29554913}, issn = {1741-7007}, abstract = {A molecular arms race is progressively being unveiled between prokaryotes and viruses. Prokaryotes utilize CRISPR-mediated adaptive immune systems to kill the invading phages and mobile genetic elements, and in turn, the viruses evolve diverse anti-CRISPR proteins to fight back. The structures of several anti-CRISPR proteins have now been reported, and here we discuss their structural features, with a particular emphasis on topology, to discover their similarities and differences. We summarize the CRISPR-Cas inhibition mechanisms of these anti-CRISPR proteins in their structural context. Considering anti-CRISPRs in this way will provide important clues for studying their origin and evolution.}, } @article {pmid29554889, year = {2018}, author = {Zhai, Y and Xu, H and Shen, Q and Schaefer, F and Schmitt, CP and Chen, J and Liu, H and Liu, J and Liu, J}, title = {pH-mediated upregulation of AQP1 gene expression through the Spi-B transcription factor.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {4}, pmid = {29554889}, issn = {1471-2199}, support = {81300635//National Natural Science Foundation of China/International ; 12ZR1441300//Shanghai Natural Science Fund for Youth Scholars/International ; 20120071120096//Young Teachers Foundation Project supported by the Doctorate in Higher Education Institutions of Ministry of Education/International ; }, mesh = {Aquaporin 1/*chemistry/*genetics ; Binding Sites ; DNA-Binding Proteins/*metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; Mutagenesis, Site-Directed ; Promoter Regions, Genetic ; Transcription Factors/*metabolism ; *Up-Regulation ; }, abstract = {BACKGROUND: Bicarbonate-based peritoneal dialysis (PD) fluids enhance the migratory capacity and damage-repair ability of human peritoneal mesothelial cells by upregulating AQP1. However, little is known about the underlying molecular mechanisms.

RESULTS: Here we used HEK-293T cells to investigate the effect of pH on AQP1 gene transcription levels. We found that AQP1 mRNA levels increases with pH. Transfection of HEK-293T cells with luciferase reporter vectors containing different regions of the AQP1 promoter identified an upstream region in the AQP1 gene between - 2200 and - 2300 bp as an enhancer required for pH-mediated regulation of AQP1 expression. Site-directed mutagenesis of this specific promoter region revealed a critical region between - 2257 and - 2251 bp, and gene knock-down experiments and ChIP assays suggested that the Spi-B transcription factor SPIB is involved in pH-mediated regulation of AQP1 expression.

CONCLUSIONS: We identified an upstream region in the AQP1 gene and the transcription factor SPIB that are critically involved in pH-mediated regulation of AQP1 expression. These findings provide the basis for further studies on the pH- and buffer-dependent effects of PD fluids on peritoneal membrane integrity and function.}, } @article {pmid29554878, year = {2018}, author = {Just, F and Oster, M and Büsing, K and Borgelt, L and Murani, E and Ponsuksili, S and Wolf, P and Wimmers, K}, title = {Lowered dietary phosphorus affects intestinal and renal gene expression to maintain mineral homeostasis with immunomodulatory implications in weaned piglets.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {207}, pmid = {29554878}, issn = {1471-2164}, support = {n.a.//LeibnizScienceCampus Phosphorus Research Rostock/International ; n.a.//LeibnizScienceCampus Phosphorus Research Rostock/International ; 311794//FP7 EU-project ECO-FCE/International ; }, mesh = {Animal Nutritional Physiological Phenomena ; Animals ; Animals, Newborn ; Colon/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; *Homeostasis ; Intestinal Mucosa/*metabolism ; Jejunum/metabolism ; Kidney/*metabolism ; Minerals/metabolism ; Phosphorus, Dietary/*administration & dosage ; Swine ; *Weaning ; }, abstract = {BACKGROUND: In monogastric animals, phosphorus (P) homeostasis is maintained by regulating intestinal absorption, bone mobilization, and renal excretion. Since P is a non-renewable resource, a shortage is imminent due to widespread over-usage in the farming and animal husbandry industries. As a consequence, P efficiency should be improved in pig production. We sought to characterize the transcriptional response in re-/absorbing and excreting tissues in pigs to diets varying in calcium: phosphorus ratios. Weaned piglets were assigned to one of three groups fed diets varying in digestible P content for a period of five weeks. Gene expression profiles were analyzed in jejunum, colon, and kidney.

RESULTS: Transcriptome analysis revealed that reduced dietary P intake affects gene expression in jejunum and kidney, but not in colon. The regulation of mineral homeostasis was reflected via altered mRNA abundances of CYP24A1, CYP27A1, TRPM6, SPP1, and VDR in jejunum and kidney. Moreover, lowered abundances of transcripts associated with the classical complement system pathway were observed in the jejunum. In kidney, shifted transcripts were involved in phospholipase C, calcium signaling, and NFAT signaling, which may have immunomodulatory implications.

CONCLUSIONS: Our results revealed local transcriptional consequences of variable P intake in intestinal and renal tissues. The adaptive responses are the result of organismal efforts to maintain systemic mineral homeostasis while modulating immune features at local tissue sites. Therefore, the deviation from the currently recommended dietary P supply must be carefully considered, as the endogenous mechanisms that respond to low P diets may impact important adaptive immune responses.}, } @article {pmid29554875, year = {2018}, author = {Zhao, L and Meng, Q and Li, Y and Wu, H and Huo, Y and Zhang, X and Zhou, Z}, title = {Nitrate decreases ruminal methane production with slight changes to ruminal methanogen composition of nitrate-adapted steers.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {21}, pmid = {29554875}, issn = {1471-2180}, abstract = {BACKGROUND: This study was conducted to examine effects of nitrate on ruminal methane production, methanogen abundance, and composition. Six rumen-fistulated Limousin×Jinnan steers were fed diets supplemented with either 0% (0NR), 1% (1NR), or 2% (2NR) nitrate (dry matter basis) regimens in succession. Rumen fluid was taken after two-week adaptation for evaluation of in vitro methane production, methanogen abundance, and composition measurements.

RESULTS: Results showed that nitrate significantly decreased in vitro ruminal methane production at 6 h, 12 h, and 24 h (P < 0.01; P < 0.01; P = 0.01). The 1NR and 2NR regimens numerically reduced the methanogen population by 4.47% and 25.82% respectively. However, there was no significant difference observed between treatments. The alpha and beta diversity of the methanogen community was not significantly changed by nitrate either. However, the relative abundance of the methanogen genera was greatly changed. Methanosphaera (PL = 0.0033) and Methanimicrococcus (PL = 0.0113) abundance increased linearly commensurate with increasing nitration levels, while Methanoplanus abundance was significantly decreased (PL = 0.0013). The population of Methanoculleus, the least frequently identified genus in this study, exhibited quadratic growth from 0% to 2% when nitrate was added (PQ = 0.0140).

CONCLUSIONS: Correlation analysis found that methane reduction was significantly related to Methanobrevibacter and Methanoplanus abundance, and negatively correlated with Methanosphaera and Methanimicrococcus abundance.}, } @article {pmid29554873, year = {2018}, author = {Pampouille, E and Berri, C and Boitard, S and Hennequet-Antier, C and Beauclercq, SA and Godet, E and Praud, C and Jégo, Y and Le Bihan-Duval, E}, title = {Mapping QTL for white striping in relation to breast muscle yield and meat quality traits in broiler chickens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {202}, pmid = {29554873}, issn = {1471-2164}, mesh = {Animals ; Body Composition ; Chickens ; Chromosome Mapping ; Female ; *Food Quality ; Genome-Wide Association Study ; Mammary Glands, Animal/*metabolism/pathology ; Meat/*analysis/standards ; Muscle Development/genetics ; Muscular Diseases/genetics/metabolism/*veterinary ; Pectoralis Muscles/metabolism ; Phenotype ; Poultry Diseases/*genetics/metabolism ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: White striping (WS) is an emerging muscular defect occurring on breast and thigh muscles of broiler chickens. It is characterized by the presence of white striations parallel to the muscle fibers and has significant consequences for meat quality. The etiology of WS remains poorly understood, even if previous studies demonstrated that the defect prevalence is related to broiler growth and muscle development. Moreover, recent studies showed moderate to high heritability values of WS, which emphasized the role of genetics in the expression of the muscle defect. The aim of this study was to identify the first quantitative trait loci (QTLs) for WS as well as breast muscle yield (BMY) and meat quality traits using a genome-wide association study (GWAS). We took advantage of two divergent lines of chickens selected for meat quality through Pectoralis major ultimate pH (pHu) and which exhibit the muscular defect. An expression QTL (eQTL) detection was further performed for some candidate genes, either suggested by GWAS analysis or based on their biological function.

RESULTS: Forty-two single nucleotide polymorphisms (SNPs) associated with WS and other meat quality traits were identified. They defined 18 QTL regions located on 13 chromosomes. These results supported a polygenic inheritance of the studied traits and highlighted a few pleiotropic regions. A set of 16 positional and/or functional candidate genes was designed for further eQTL detection. A total of 132 SNPs were associated with molecular phenotypes and defined 21 eQTL regions located on 16 chromosomes. Interestingly, several co-localizations between QTL and eQTL regions were observed which could suggest causative genes and gene networks involved in the variability of meat quality traits and BMY.

CONCLUSIONS: The QTL mapping carried out in the current study for WS did not support the existence of a major gene, but rather suggested a polygenic inheritance of the defect and of other studied meat quality traits. We identified several candidate genes involved in muscle metabolism and structure and in muscular dystrophies. The eQTL analyses showed that they were part of molecular networks associated with WS and meat quality phenotypes and suggested a few putative causative genes.}, } @article {pmid29554870, year = {2018}, author = {Greninger, AL and Knudsen, GM and Roychoudhury, P and Hanson, DJ and Sedlak, RH and Xie, H and Guan, J and Nguyen, T and Peddu, V and Boeckh, M and Huang, ML and Cook, L and Depledge, DP and Zerr, DM and Koelle, DM and Gantt, S and Yoshikawa, T and Caserta, M and Hill, JA and Jerome, KR}, title = {Comparative genomic, transcriptomic, and proteomic reannotation of human herpesvirus 6.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {204}, pmid = {29554870}, issn = {1471-2164}, support = {K23 AI119133/AI/NIAID NIH HHS/United States ; K24 HL093294/HL/NHLBI NIH HHS/United States ; P50 GM115305/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Child ; Child, Preschool ; Cohort Studies ; Female ; Gene Expression Profiling/*methods ; Genome, Viral ; Genomics/*methods ; Global Health ; Herpesvirus 6, Human/*genetics/isolation & purification/*metabolism ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Proteomics/methods ; Roseolovirus Infections/*virology ; Viral Proteins/*analysis ; Young Adult ; }, abstract = {BACKGROUND: Human herpesvirus-6A and -6B (HHV-6) are betaherpesviruses that reach > 90% seroprevalence in the adult population. Unique among human herpesviruses, HHV-6 can integrate into the subtelomeric regions of human chromosomes; when this occurs in germ line cells it causes a condition called inherited chromosomally integrated HHV-6 (iciHHV-6). Only two complete genomes are available for replicating HHV-6B, leading to numerous conflicting annotations and little known about the global genomic diversity of this ubiquitous virus.

RESULTS: Using a custom capture panel for HHV-6B, we report complete genomes from 61 isolates of HHV-6B from active infections (20 from Japan, 35 from New York state, and 6 from Uganda), and 64 strains of iciHHV-6B (mostly from North America). HHV-6B sequence clustered by geography and illustrated extensive recombination. Multiple iciHHV-6B sequences from unrelated individuals across the United States were found to be completely identical, consistent with a founder effect. Several iciHHV-6B strains clustered with strains from recent active pediatric infection. Combining our genomic analysis with the first RNA-Seq and shotgun proteomics studies of HHV-6B, we completely reannotated the HHV-6B genome, altering annotations for more than 10% of existing genes, with multiple instances of novel splicing and genes that hitherto had gone unannotated.

CONCLUSION: Our results are consistent with a model of intermittent de novo integration of HHV-6B into host germline cells during active infection with a large contribution of founder effect in iciHHV-6B. Our data provide a significant advance in the genomic annotation of HHV-6B, which will contribute to the detection, diversity, and control of this virus.}, } @article {pmid29554868, year = {2018}, author = {Gouil, Q and Baulcombe, DC}, title = {Paramutation-like features of multiple natural epialleles in tomato.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {203}, pmid = {29554868}, issn = {1471-2164}, support = {340642//European Research Council/International ; ERC-2013-AdG 340642//European Research Council/International ; Frank Smart Studentship//Department of Plant Sciences, University of Cambridge (GB)/International ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Alleles ; *DNA Methylation ; *Epigenesis, Genetic ; *Gene Silencing ; Lycopersicon esculentum/*genetics ; *Mutation ; RNA, Small Interfering/*genetics ; Transgenes ; }, abstract = {BACKGROUND: Freakish and rare or the tip of the iceberg? Both phrases have been used to refer to paramutation, an epigenetic drive that contravenes Mendel's first law of segregation. Although its underlying mechanisms are beginning to unravel, its understanding relies only on a few examples that may involve transgenes or artificially generated epialleles.

RESULTS: By using DNA methylation of introgression lines as an indication of past paramutation, we reveal that the paramutation-like properties of the H06 locus in hybrids of Solanum lycopersicum and a range of tomato relatives and cultivars depend on the timing of sRNA production and conform to an RNA-directed mechanism. In addition, by scanning the methylomes of tomato introgression lines for shared regions of differential methylation that are absent in the S. lycopersicum parent, we identify thousands of candidate regions for paramutation-like behaviour. The methylation patterns for a subset of these regions segregate with non Mendelian ratios, consistent with secondary paramutation-like interactions to variable extents depending on the locus.

CONCLUSION: Together these results demonstrate that paramutation-like epigenetic interactions are common for natural epialleles in tomato, but vary in timing and penetrance.}, } @article {pmid29554865, year = {2018}, author = {Li, J and He, YJ and Zhou, L and Liu, Y and Jiang, M and Ren, L and Chen, H}, title = {Transcriptome profiling of genes related to light-induced anthocyanin biosynthesis in eggplant (Solanum melongena L.) before purple color becomes evident.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {201}, pmid = {29554865}, issn = {1471-2164}, support = {31471870//National Natural Science Foundation of China/International ; }, mesh = {Anthocyanins/*metabolism ; Fruit/genetics/metabolism/radiation effects ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Developmental ; Gene Expression Regulation, Plant ; Light ; Pigmentation ; Plant Proteins/*genetics ; Solanum melongena/*genetics/metabolism/radiation effects ; Transcriptome/radiation effects ; }, abstract = {BACKGROUND: The anthocyanins are highly enriched in eggplants (Solanum melongena L.) with purple peel. However, our previous study showed that anthocyanins biosynthesis in eggplant cultivar 'Lanshan Hexian' was completely regulated by light and color becomes evident at most 2 days after exposure to light. In the present investigation, transcriptome study was made to explore the underlying molecular mechanisms of light-induced anthocyanin biosynthesis in eggplant (Solanum melongena L.) before color becomes evident.

RESULTS: RNA-Seq was performed for four time points (0, 0.5, 4 and 8 h after bags removal) where concerted changes happened. A total of 32,630 genes or transcripts were obtained by transcriptome sequencing, from which 1956 differentially expressed genes (DEGs) were found. Gene Ontology analysis showed that the 1956 DEGs covered a wide range of cellular components, molecular functions and biological processes. All the DEGs were further divided into 26 clusters based on their distinct expression patterns. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis found out 24 structural anthocyanin biosynthesis genes which distributing in seven clusters. In addition, 102 transcription factors, which exhibited highly dynamic changes in response to light, were found in the seven clusters. Three photoreceptors, UV Resistance Locus 8 (UVR8), Cryptochrome 3 (CRY3) and UVR3, were identified as DEGs. The light signal transduction elements, COP1 and two SPAs, might be responsible for anthocyanin biosynthesis regulation.

CONCLUSION: Based on the transcriptome data, the anthocyanin biosynthesis structural genes, transcription factors, photoreceptors and light signal transduction elements were quickly screened which may act as the key regulatory factors in anthocyanin biosynthesis pathway. By comparing the transcriptome data with our previous studies, 869 genes were confirmed to participate in the light-induced anthocyanin biosynthesis. These results expand our knowledge of light-induced anthocyanin biosynthesis in plants, which allowing for fruit coloration to be improved under low-light conditions in future.}, } @article {pmid29554864, year = {2018}, author = {Stefanovic, E and McAuliffe, O}, title = {Comparative genomic and metabolic analysis of three Lactobacillus paracasei cheese isolates reveals considerable genomic differences in strains from the same niche.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {205}, pmid = {29554864}, issn = {1471-2164}, support = {6224//Teagasc/International ; }, mesh = {Animals ; Cheese/analysis/*microbiology ; DNA, Bacterial/genetics ; *Genetic Variation ; Genome, Bacterial ; Genomics/*methods ; Lactobacillus paracasei/classification/*genetics/isolation & purification/*metabolism ; Metabolomics/*methods ; Phylogeny ; }, abstract = {BACKGROUND: Strains of Lactobacillus paracasei are present in many diverse environments, including dairy and plant materials and the intestinal tracts of humans and animals. Their adaptation to various niches is correlated to intra-species diversity at the genomic and metabolic level. In this study, we compared the genome sequences of three L. paracasei strains isolated from mature Cheddar cheeses, two of which (DPC4206 and DPC4536) shared the same genomic fingerprint by PFGE, but demonstrated varying metabolic capabilities.

RESULTS: Genome sizes varied from 2.9 Mbp for DPC2071, to 3.09 Mbp for DPC4206 and 3.08 Mpb for DPC4536. The presence of plasmids was a distinguishing feature between the strains with strain DPC2071 possessing an unusually high number of plasmids (up to 11), while DPC4206 had one plasmid and DPC4536 harboured no plasmids. Each of the strains possessed specific genes not present in the other two analysed strains. The three strains differed in their abundance of sugar-converting genes, and in the types of sugars that could be used as energy sources. Genes involved in the metabolism of sugars not usually connected with the dairy niche, such as myo-inositol and pullulan were also detected, but strains did not utilise these sugars. The genetic content of the three strains differed in regard to specific genes for arginine and sulfur-containing amino acid metabolism and genes contributing to resistance to heavy metal ions. In addition, variability in the presence of phage remnants and phage protection systems was evident.

CONCLUSIONS: The findings presented in this study confirm a considerable level of heterogeneity of Lactobacillus paracasei strains, even between strains isolated from the same niche.}, } @article {pmid29554332, year = {2018}, author = {Lloyd, JP and Tsai, ZT and Sowers, RP and Panchy, NL and Shiu, SH}, title = {A Model-Based Approach for Identifying Functional Intergenic Transcribed Regions and Noncoding RNAs.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1422-1436}, doi = {10.1093/molbev/msy035}, pmid = {29554332}, issn = {1537-1719}, abstract = {With advances in transcript profiling, the presence of transcriptional activities in intergenic regions has been well established. However, whether intergenic expression reflects transcriptional noise or activity of novel genes remains unclear. We identified intergenic transcribed regions (ITRs) in 15 diverse flowering plant species and found that the amount of intergenic expression correlates with genome size, a pattern that could be expected if intergenic expression is largely nonfunctional. To further assess the functionality of ITRs, we first built machine learning models using Arabidopsis thaliana as a model that accurately distinguish functional sequences (benchmark protein-coding and RNA genes) and likely nonfunctional ones (pseudogenes and unexpressed intergenic regions) by integrating 93 biochemical, evolutionary, and sequence-structure features. Next, by applying the models genome-wide, we found that 4,427 ITRs (38%) and 796 annotated ncRNAs (44%) had features significantly similar to benchmark protein-coding or RNA genes and thus were likely parts of functional genes. Approximately 60% of ITRs and ncRNAs were more similar to nonfunctional sequences and were likely transcriptional noise. The predictive framework established here provides not only a comprehensive look at how functional, genic sequences are distinct from likely nonfunctional ones, but also a new way to differentiate novel genes from genomic regions with noisy transcriptional activities.}, } @article {pmid29554291, year = {2018}, author = {Warshan, D and Liaimer, A and Pederson, E and Kim, SY and Shapiro, N and Woyke, T and Altermark, B and Pawlowski, K and Weyman, PD and Dupont, CL and Rasmussen, U}, title = {Genomic Changes Associated with the Evolutionary Transitions of Nostoc to a Plant Symbiont.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1160-1175}, pmid = {29554291}, issn = {1537-1719}, abstract = {Cyanobacteria belonging to the genus Nostoc comprise free-living strains and also facultative plant symbionts. Symbiotic strains can enter into symbiosis with taxonomically diverse range of host plants. Little is known about genomic changes associated with evolutionary transition of Nostoc from free-living to plant symbiont. Here, we compared the genomes derived from 11 symbiotic Nostoc strains isolated from different host plants and infer phylogenetic relationships between strains. Phylogenetic reconstructions of 89 Nostocales showed that symbiotic Nostoc strains with a broad host range, entering epiphytic and intracellular or extracellular endophytic interactions, form a monophyletic clade indicating a common evolutionary history. A polyphyletic origin was found for Nostoc strains which enter only extracellular symbioses, and inference of transfer events implied that this trait was likely acquired several times in the evolution of the Nostocales. Symbiotic Nostoc strains showed enriched functions in transport and metabolism of organic sulfur, chemotaxis and motility, as well as the uptake of phosphate, branched-chain amino acids, and ammonium. The genomes of the intracellular clade differ from that of other Nostoc strains, with a gain/enrichment of genes encoding proteins to generate l-methionine from sulfite and pathways for the degradation of the plant metabolites vanillin and vanillate, and of the macromolecule xylan present in plant cell walls. These compounds could function as C-sources for members of the intracellular clade. Molecular clock analysis indicated that the intracellular clade emerged ca. 600 Ma, suggesting that intracellular Nostoc symbioses predate the origin of land plants and the emergence of their extant hosts.}, } @article {pmid29553801, year = {2018}, author = {Tardieu, F and Simonneau, T and Muller, B}, title = {The Physiological Basis of Drought Tolerance in Crop Plants: A Scenario-Dependent Probabilistic Approach.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {733-759}, doi = {10.1146/annurev-arplant-042817-040218}, pmid = {29553801}, issn = {1545-2123}, abstract = {Drought tolerance involves mechanisms operating at different spatial and temporal scales, from rapid stomatal closure to maintenance of crop yield. We review how short-term mechanisms are controlled for stabilizing shoot water potential and how long-term processes have been constrained by evolution or breeding to fit into acclimation strategies for specific drought scenarios. These short- or long-term feedback processes participate in trade-offs between carbon accumulation and the risk of deleterious soil water depletion. Corresponding traits and alleles may therefore have positive or negative effects on crop yield depending on drought scenarios. We propose an approach that analyzes the genetic architecture of traits in phenotyping platforms and of yield in tens of field experiments. A combination of modeling and genomic prediction is then used to estimate the comparative interests of combinations of alleles depending on drought scenarios. Hence, drought tolerance is understood probabilistically by estimating the benefit and risk of each combination of alleles.}, } @article {pmid29553800, year = {2018}, author = {Wang, B and Smith, SM and Li, J}, title = {Genetic Regulation of Shoot Architecture.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {437-468}, doi = {10.1146/annurev-arplant-042817-040422}, pmid = {29553800}, issn = {1545-2123}, abstract = {Shoot architecture is determined by the organization and activities of apical, axillary, intercalary, secondary, and inflorescence meristems and by the subsequent development of stems, leaves, shoot branches, and inflorescences. In this review, we discuss the unifying principles of hormonal and genetic control of shoot architecture including advances in our understanding of lateral branch outgrowth; control of stem elongation, thickness, and angle; and regulation of inflorescence development. We focus on recent progress made mainly in Arabidopsis thaliana, rice, pea, maize, and tomato, including the identification of new genes and mechanisms controlling shoot architecture. Key advances include elucidation of mechanisms by which strigolactones, auxins, and genes such as IDEAL PLANT ARCHITECTURE1 and TEOSINTE BRANCHED1 control shoot architecture. Knowledge now available provides a foundation for rational approaches to crop breeding and the generation of ideotypes with defined architectural features to improve performance and productivity.}, } @article {pmid29551886, year = {2018}, author = {Karumathil, S and Raveendran, NT and Ganesh, D and Kumar Ns, S and Nair, RR and Dirisala, VR}, title = {Evolution of Synonymous Codon Usage Bias in West African and Central African Strains of Monkeypox Virus.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318761368}, pmid = {29551886}, issn = {1176-9343}, abstract = {The evolution of bias in synonymous codon usage in chosen monkeypox viral genomes and the factors influencing its diversification have not been reported so far. In this study, various trends associated with synonymous codon usage in chosen monkeypox viral genomes were investigated, and the results are reported. Identification of factors that influence codon usage in chosen monkeypox viral genomes was done using various codon usage indices, such as the relative synonymous codon usage, the effective number of codons, and the codon adaptation index. The Spearman rank correlation analysis and a correspondence analysis were used for correlating various factors with codon usage. The results revealed that mutational pressure due to compositional constraints, gene expression level, and selection at the codon level for utilization of putative optimal codons are major factors influencing synonymous codon usage bias in monkeypox viral genomes. A cluster analysis of relative synonymous codon usage values revealed a grouping of more virulent strains as one major cluster (Central African strains) and a grouping of less virulent strains (West African strains) as another major cluster, indicating a relationship between virulence and synonymous codon usage bias. This study concluded that a balance between the mutational pressure acting at the base composition level and the selection pressure acting at the amino acid level frames synonymous codon usage bias in the chosen monkeypox viruses. The natural selection from the host does not seem to have influenced the synonymous codon usage bias in the analyzed monkeypox viral genomes.}, } @article {pmid29551885, year = {2018}, author = {Yang, CH and Wu, KC and Chuang, LY and Chang, HW}, title = {Decision Tree Algorithm-Generated Single-Nucleotide Polymorphism Barcodes of rbcL Genes for 38 Brassicaceae Species Tagging.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318760856}, pmid = {29551885}, issn = {1176-9343}, abstract = {DNA barcode sequences are accumulating in large data sets. A barcode is generally a sequence larger than 1000 base pairs and generates a computational burden. Although the DNA barcode was originally envisioned as straightforward species tags, the identification usage of barcode sequences is rarely emphasized currently. Single-nucleotide polymorphism (SNP) association studies provide us an idea that the SNPs may be the ideal target of feature selection to discriminate between different species. We hypothesize that SNP-based barcodes may be more effective than the full length of DNA barcode sequences for species discrimination. To address this issue, we tested a ribulose diphosphate carboxylase (rbcL) SNP barcoding (RSB) strategy using a decision tree algorithm. After alignment and trimming, 31 SNPs were discovered in the rbcL sequences from 38 Brassicaceae plant species. In the decision tree construction, these SNPs were computed to set up the decision rule to assign the sequences into 2 groups level by level. After algorithm processing, 37 nodes and 31 loci were required for discriminating 38 species. Finally, the sequence tags consisting of 31 rbcL SNP barcodes were identified for discriminating 38 Brassicaceae species based on the decision tree-selected SNP pattern using RSB method. Taken together, this study provides the rational that the SNP aspect of DNA barcode for rbcL gene is a useful and effective sequence for tagging 38 Brassicaceae species.}, } @article {pmid29551830, year = {2018}, author = {York, A}, title = {Archaeal physiology: Alien methanogens on Saturn's moon?.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {261}, pmid = {29551830}, issn = {1740-1534}, } @article {pmid29551829, year = {2018}, author = {Hofer, U}, title = {Environmental microbiology: New diversity in the sulfur cycle.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {260-261}, pmid = {29551829}, issn = {1740-1534}, } @article {pmid29551828, year = {2018}, author = {York, A}, title = {Environmental microbiology: Soil surface communities bite the dust.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {261}, doi = {10.1038/nrmicro.2018.34}, pmid = {29551828}, issn = {1740-1534}, } @article {pmid29551827, year = {2018}, author = {York, A}, title = {Microbiome: Viral hormones activate human insulin signalling.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {261}, pmid = {29551827}, issn = {1740-1534}, } @article {pmid29551694, year = {2018}, author = {Hemmi, N and Akiyama-Oda, Y and Fujimoto, K and Oda, H}, title = {A quantitative study of the diversity of stripe-forming processes in an arthropod cell-based field undergoing axis formation and growth.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {84-104}, doi = {10.1016/j.ydbio.2018.03.001}, pmid = {29551694}, issn = {1095-564X}, mesh = {Animals ; Arthropods/embryology/genetics ; Body Patterning/*genetics/physiology ; Cell Count ; Embryonic Development/genetics/physiology ; Gene Expression Regulation, Developmental ; Hedgehog Proteins/*metabolism ; In Situ Hybridization, Fluorescence ; Spiders/*embryology/metabolism ; }, abstract = {One of the conserved traits of arthropod embryonic development is striped expression of homologs of Drosophila segment polarity genes, including hedgehog (hh). Although a diversity of stripe-forming processes is recognized among arthropod embryos, such varied stripe-forming processes have not been well characterized from cellular and quantitative perspectives. The spider Parasteatoda tepidariorum embryo, which has a hh-dependent mechanism of axis formation, offers a cell-based field where the stripes of Pt-hh (a hh homolog) expression dynamically develop in accordance with axis formation and growth, with the patterning processes varying among the regions of the field. In this study, using cell labeling, we mapped the future body subdivisions to the germ disc in the spider embryo and provided substantial evidence for the occurrence of kinetic waves of Pt-hh expression in the presumptive head and opisthosomal (or abdominal) regions of the embryonic field. Notably, combined with cell tracking, we showed that surface cells at and near the center of the germ disc persist in the posterior portion of the field from where Pt-hh stripes sequentially arise, suggesting the operation of ordered oscillations of Pt-hh expression. We then conducted a quantitative analysis of forming/formed Pt-hh stripes using serially timed fixation of sibling embryos. By utilizing length measurements that reflect the axis growth of the embryonic field, we reconstructed the pattern dynamics, which captured repeated splitting of Pt-hh stripes and oscillations of Pt-hh expression in the presumptive head and opisthosomal regions, respectively. In the intermediate thoracic region, three stripes of Pt-hh expression showed a late appearance, with the segmental units specified much earlier by another mechanism. Analyses provided quantitative estimates related to axis growth and stripe-splitting and oscillation events, including the periods of the patterning cycles. This work characterizes the diversity of stripe-forming processes in a cell-based field in a common spatiotemporal framework and highlights the contrasting dynamics of splitting versus oscillation. The cellular and quantitative data presented here provide the foundation for experimental, theoretical and evolutionary studies of cell-based pattern formation, especially body axis segmentation in arthropods.}, } @article {pmid29551526, year = {2018}, author = {Santos, JC and Tarvin, RD and O'Connell, LA and Blackburn, DC and Coloma, LA}, title = {Diversity within diversity: Parasite species richness in poison frogs assessed by transcriptomics.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {40-50}, doi = {10.1016/j.ympev.2018.03.015}, pmid = {29551526}, issn = {1095-9513}, mesh = {Animals ; Anura/*genetics/*parasitology ; Biodiversity ; *Gene Expression Profiling ; Genetic Speciation ; Host-Parasite Interactions/genetics ; Parasites/*physiology ; Phylogeny ; Poisons ; Species Specificity ; Transcriptome/genetics ; }, abstract = {Symbionts (e.g., endoparasites and commensals) play an integral role in their host's ecology, yet in many cases their diversity is likely underestimated. Although endoparasites are traditionally characterized using morphology, sequences of conserved genes, and shotgun metagenomics, host transcriptomes constitute an underused resource to identify these organisms' diversity. By isolating non-host transcripts from host transcriptomes, individual host tissues can now simultaneously reveal their endoparasite species richness (i.e., number of different taxa) and provide insights into parasite gene expression. These approaches can be used in host taxa whose endoparasites are mostly unknown, such as those of tropical amphibians. Here, we focus on the poison frogs (Dendrobatidae) as hosts, which are a Neotropical clade known for their bright coloration and defensive alkaloids. These toxins are an effective protection against vertebrate predators (e.g., snakes and birds), bacteria, and skin-biting ectoparasites (e.g., mosquitoes); however, little is known about their deterrence against eukaryotic endoparasites. With de novo transcriptomes of dendrobatids, we developed a bioinformatics pipeline for endoparasite identification that uses host annotated RNA-seq data and set of a priori parasite taxonomic terms, which are used to mine for specific endoparasites. We found a large community of helminths and protozoans that were mostly restricted to the digestive tract and a few systemic parasites (e.g., Trypanosoma). Contrary to our expectations, all dendrobatid frogs regardless of the presence of alkaloid defenses have endoparasites, with their highest species richness located in the frog digestive tract. Some of these organisms (e.g., roundworms) might prove to be generalists, as they were not found to be co-diversifying with their frog hosts. We propose that endoparasites may escape poison frogs' chemical defenses by colonizing tissues with fewer alkaloids than the frog's skin, where most toxins are stored.}, } @article {pmid29551525, year = {2018}, author = {Tallowin, OJS and Tamar, K and Meiri, S and Allison, A and Kraus, F and Richards, SJ and Oliver, PM}, title = {Early insularity and subsequent mountain uplift were complementary drivers of diversification in a Melanesian lizard radiation (Gekkonidae: Cyrtodactylus).}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {29-39}, doi = {10.1016/j.ympev.2018.03.020}, pmid = {29551525}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Biodiversity ; *Biological Evolution ; Genetic Variation ; Geography ; Lizards/genetics/*physiology ; Papua New Guinea ; Phylogeny ; Time Factors ; }, abstract = {Regions with complex geological histories present a major challenge for scientists studying the processes that have shaped their biotas. The history of the vast and biologically rich tropical island of New Guinea is particularly complex and poorly resolved. Competing geological models propose New Guinea emerged as a substantial landmass either during the Mid-Miocene or as recently as the Pliocene. Likewise, the estimated timing for the uplift of the high Central Cordillera, spanning the length of the island, differs across models. Here we investigate how early islands and mountain uplift have shaped the diversification and biogeography of Cyrtodactylus geckos. Our data strongly support initial colonisation and divergence within proto-Papuan islands in the Early- to Mid-Miocene, with divergent lineages and endemic diversity concentrated on oceanic island arcs in northern New Guinea and the formerly isolated East-Papuan Composite Terrane. At least four lineages are inferred to have independently colonised hill- and lower-montane forests, indicating that mountain uplift has also played a critical role in accumulating diversity, even in this predominantly lowland lineage. Our findings suggest that substantial land in northern New Guinea and lower-montane habitats date back well into the Miocene and that insular diversification and mountain colonisation have synergistically generated diversity in the geologically complex Papuan region.}, } @article {pmid29551524, year = {2018}, author = {Barros-García, D and Froufe, E and Bañón, R and Carlos Arronte, J and de Carlos, A}, title = {Phylogenetic analysis shows the general diversification pattern of deep-sea notacanthiforms (Teleostei: Elopomorpha).}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {192-198}, doi = {10.1016/j.ympev.2018.03.007}, pmid = {29551524}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Biodiversity ; Calibration ; Evolution, Molecular ; Fishes/*classification/genetics ; Genes, Mitochondrial ; *Oceans and Seas ; *Phylogeny ; Time Factors ; }, abstract = {The Notacanthiformes is an ancient group of deep-sea ray-finned fishes comprising 27 species in two families; Halosauridae and Notacanthidae. Although many studies have tried to reconstruct the phylogenetic relationships among the major clades of Elopomorpha, little is known about the evolutionary history of notacanthiforms. Molecular and morphological data were used to test previous hypotheses regarding the phylogenetic relationships among notacanthiform taxa, and to unravel the origin and evolution of this group. The molecular analyses of notacanthids showed similar results to those previously obtained employing osteological data, which proposed the existence of the Lipogenyinae (Lipogenys) and Notacanthinae (Notacanthus + Polyacanthonotus) subfamilies. Nevertheless, when the external morphology data is considered Lipogenys is more related to Notacanthus than Polyacanthonotus. The analyses could not fully resolve the inner relationships of the halosaurids. The time-calibrated tree of the order Notacanthiformes shows a long process of diversification spanning from the upper Cretaceous, to 50 million years after the K-Pg extinction, with the gradual emergence of all the modern families and genera of the group. This is the first specific phylogeny of the order Notacanthiformes, combining different analyses and data in order to obtain a wider perspective of the evolution and diversification of this group of fishes.}, } @article {pmid29551523, year = {2018}, author = {Portillo, F and Branch, WR and Conradie, W and Rödel, MO and Penner, J and Barej, MF and Kusamba, C and Muninga, WM and Aristote, MM and Bauer, AM and Trape, JF and Nagy, ZT and Carlino, P and Pauwels, OSG and Menegon, M and Burger, M and Mazuch, T and Jackson, K and Hughes, DF and Behangana, M and Zassi-Boulou, AG and Greenbaum, E}, title = {Phylogeny and biogeography of the African burrowing snake subfamily Aparallactinae (Squamata: Lamprophiidae).}, journal = {Molecular phylogenetics and evolution}, volume = {127}, number = {}, pages = {288-303}, doi = {10.1016/j.ympev.2018.03.019}, pmid = {29551523}, issn = {1095-9513}, support = {G12 RR008124/RR/NCRR NIH HHS/United States ; G12 MD007592/MD/NIMHD NIH HHS/United States ; }, abstract = {Members of the snake subfamily Aparallactinae occur in various habitats throughout sub-Saharan Africa. The monophyly of aparallactine snakes is well established, but relationships within the subfamily are poorly known. We sampled 158 individuals from six of eight aparallactine genera in sub-Saharan Africa. We employed concatenated gene-tree analyses, divergence dating approaches, and ancestral-area reconstructions to infer phylogenies and biogeographic patterns with a multi-locus data set consisting of three mitochondrial (16S, cyt b, and ND4) and two nuclear genes (c-mos and RAG1). As a result, we uncover several cryptic lineages and elevate a lineage of Polemon to full species status. Diversification occurred predominantly during the Miocene, with a few speciation events occurring subsequently in the Pliocene and Pleistocene. Biogeographic analyses suggested that the Zambezian biogeographic region, comprising grasslands and woodlands, facilitated radiations, vicariance, and dispersal for many aparallactines. Moreover, the geographic distributions of many forest species were fragmented during xeric and cooler conditions, which likely led to diversification events. Biogeographic patterns of aparallactine snakes are consistent with previous studies of other sub-Saharan herpetofauna.}, } @article {pmid29551522, year = {2018}, author = {Egan, JP and Bloom, DD and Kuo, CH and Hammer, MP and Tongnunui, P and Iglésias, SP and Sheaves, M and Grudpan, C and Simons, AM}, title = {Phylogenetic analysis of trophic niche evolution reveals a latitudinal herbivory gradient in Clupeoidei (herrings, anchovies, and allies).}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {151-161}, doi = {10.1016/j.ympev.2018.03.011}, pmid = {29551522}, issn = {1095-9513}, mesh = {Animals ; Calibration ; Diet ; *Ecosystem ; Fishes/*physiology ; Herbivory/*physiology ; *Phylogeny ; Species Specificity ; Time Factors ; }, abstract = {Biotic and abiotic forces govern the evolution of trophic niches, which profoundly impact ecological and evolutionary processes and aspects of species biology. Herbivory is a particularly interesting trophic niche because there are theorized trade-offs associated with diets comprised of low quality food that might prevent the evolution of herbivory in certain environments. Herbivory has also been identified as a potential evolutionary "dead-end" that hinders subsequent trophic diversification. For this study we investigated trophic niche evolution in Clupeoidei (anchovies, sardines, herrings, and their relatives) and tested the hypotheses that herbivory is negatively correlated with salinity and latitude using a novel, time-calibrated molecular phylogeny, trophic guilds delimited using diet data and cluster analysis, and standard and phylogenetically-informed statistical methods. We identified eight clupeoid trophic guilds: molluscivore, terrestrial invertivore, phytoplanktivore, macroalgivore, detritivore, piscivore, crustacivore, and zooplanktivore. Standard statistical methods found a significant negative correlation between latitude and the proportion of herbivorous clupeoids (herbivorous clupeoid species/total clupeoid species), but no significant difference in the proportion of herbivorous clupeoids between freshwater and marine environments. Phylogenetic least squares regression did not identify significant negative correlations between latitude and herbivory or salinity and herbivory. In clupeoids there were five evolutionary transitions from non-herbivore to herbivore guilds and no transitions from herbivore to non-herbivore guilds. There were no transitions to zooplanktivore, the most common guild, but it gave rise to all trophic guilds, except algivore, at least once. Transitions to herbivory comprised a significantly greater proportion of diet transitions in tropical and subtropical (<35°) relative to temperate areas (>35°). Our findings suggest cold temperatures may constrain the evolution of herbivory and that herbivory might act as an evolutionary "dead-end" that hinders subsequent trophic diversification, while zooplanktivory acts as an evolutionary "cradle" that facilitates trophic diversification.}, } @article {pmid29551521, year = {2018}, author = {Smith, BT and Bryson, RW and Mauck, WM and Chaves, J and Robbins, MB and Aleixo, A and Klicka, J}, title = {Species delimitation and biogeography of the gnatcatchers and gnatwrens (Aves: Polioptilidae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {45-57}, doi = {10.1016/j.ympev.2018.03.012}, pmid = {29551521}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Passeriformes/*classification/genetics ; Phylogeny ; *Phylogeography ; Probability ; Species Specificity ; }, abstract = {The New World avian family Polioptilidae (gnatcatchers and gnatwrens) is distributed from Argentina to Canada and includes 15 species and more than 60 subspecies. No study to date has evaluated phylogenetic relationships within this family and the historical pattern of diversification within the group remains unknown. Moreover, species limits, particularly in widespread taxa that show geographic variation, remain unclear. In this study, we delimited species and estimated phylogenetic relationships using multilocus data for the entire family. We then used the inferred diversity along with alternative taxonomic classification schemes to evaluate how lumping and splitting of both taxa and geographical areas influenced biogeographic inference. Species-tree analyses grouped Polioptilidae into four main clades: Microbates, Ramphocaenus, a Polioptila guianensis complex, and the remaining members of Polioptila. Ramphocaenus melanurus was sister to the clade containing M. cinereiventris and M. collaris, which formed a clade sister to all species within Polioptila. Polioptila was composed of two clades, the first of which included the P. guianensis complex; the other contained all remaining species in the genus. Using multispecies coalescent modeling, we inferred a more than 3-fold increase in species diversity, of which 87% represent currently recognized species or subspecies. Much of this diversity corresponded to subspecies that occur in the Neotropics. We identified three polyphyletic species, and delimited 4-6 previously undescribed candidate taxa. Probabilistic modeling of geographic ranges on the species tree indicated that the family likely had an ancestral origin in South America, with all three genera independently colonizing North America. Support for this hypothesis, however, was sensitive to the taxonomic classification scheme used and the number of geographical areas allowed. Our study proposes the first phylogenetic hypothesis for Polioptilidae and provides genealogical support for the reclassification of species limits. Species limits and the resolution of geographical areas that taxa inhabit influence the inferred spatial diversification history.}, } @article {pmid29551520, year = {2018}, author = {Semerikova, SA and Khrunyk, YY and Lascoux, M and Semerikov, VL}, title = {From America to Eurasia: a multigenomes history of the genus Abies.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {14-28}, doi = {10.1016/j.ympev.2018.03.009}, pmid = {29551520}, issn = {1095-9513}, mesh = {Abies/classification/*genetics ; Americas ; Asia ; Bayes Theorem ; Cell Nucleus/genetics ; DNA, Chloroplast/genetics ; DNA, Mitochondrial/genetics ; Ecotype ; Europe ; *Genome, Plant ; Geography ; Phylogeny ; Time Factors ; }, abstract = {The origin of conifer genera, the main components of mountain temperate and boreal forests, was deemed to arise in the Mesozoic, although paleontological records and molecular data point to a recent diversification, presumably related to Neogene cooling. The geographical area(s) where the modern lines of conifers emerged remains uncertain, as is the sequence of events leading to their present distribution. To gain further insights into the biogeography of firs (Abies), we conducted phylogenetic analyses of chloroplast, mitochondrial and nuclear markers. The species tree, generated from ten single-copy nuclear genes, yielded probably the best phylogenetic hypothesis available for Abies. The tree obtained from five regions of chloroplast DNA largely corresponded to the nuclear species tree. Ancestral area reconstructions based on fossil calibrated chloroplast DNA and nuclear DNA trees pointed to repeated intercontinental migrations. The mitochondrial DNA haplotype tree, however, disagreed with nuclear and chloroplast DNA trees. It consisted of two clusters: one included mainly American haplotypes, while the other was composed of only Eurasian haplotypes. Presumably, this conflict is due to inter-continental migrations and introgressive hybridization, accompanied by the capture of the mitotypes from aboriginal species by the invading firs. Given that several species inhabiting Northeastern Asia carry American mitotypes and mutations typical for the American cluster, whereas no Asian mitotypes were detected within the American species, we hypothesize that Abies migrated from America to Eurasia, but not in the opposite direction. The direction and age of intercontinental migrations in firs are congruent with other conifers, such as spruces and pines of subsection Strobus, suggesting that these events had the same cause.}, } @article {pmid29551358, year = {2018}, author = {Evans, MV and Murdock, CC and Drake, JM}, title = {Anticipating Emerging Mosquito-borne Flaviviruses in the USA: What Comes after Zika?.}, journal = {Trends in parasitology}, volume = {34}, number = {7}, pages = {544-547}, pmid = {29551358}, issn = {1471-5007}, support = {U01 GM110744/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Communicable Diseases, Emerging/epidemiology/prevention & control/virology ; Flavivirus/*physiology ; *Flavivirus Infections/epidemiology/prevention & control/virology ; Health Policy/trends ; Humans ; *Models, Theoretical ; Mosquito Vectors/*virology ; *Public Health Surveillance ; United States/epidemiology ; Zika Virus Infection ; }, abstract = {New mosquito-borne diseases have emerged on multiple occasions over the last several decades, raising fears that there are yet more poorly understood viruses that may emerge in the USA. Here, we provide a data-driven 'watch list' of viruses in the Flaviviridae family with high potential to emerge in the USA, identified using statistical techniques, to enable the public health community to better target surveillance. We suggest that public health authorities further incorporate predictive modeling techniques into disease-prevention strategies.}, } @article {pmid29550535, year = {2018}, author = {Liu, B and Le, CT and Barrett, RL and Nickrent, DL and Chen, Z and Lu, L and Vidal-Russell, R}, title = {Historical biogeography of Loranthaceae (Santalales): Diversification agrees with emergence of tropical forests and radiation of songbirds.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {199-212}, doi = {10.1016/j.ympev.2018.03.010}, pmid = {29550535}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Chloroplast/genetics ; *Forests ; Loranthaceae/*classification ; Phylogeny ; *Phylogeography ; Songbirds/*physiology ; Time Factors ; *Tropical Climate ; }, abstract = {Coadaptation between mistletoes and birds captured the attention of Charles Darwin over 150 years ago, stimulating considerable scientific research. Here we used Loranthaceae, a speciose and ecologically important mistletoe family, to obtain new insights into the interrelationships among its hosts and dispersers. Phylogenetic analyses of Loranthaceae were based on a dataset of nuclear and chloroplast DNA sequences. Divergence time estimation, ancestral area reconstruction, and diversification rate analyses were employed to examine historical biogeography. The crown group of Loranthaceae was estimated to originate in Australasian Gondwana during the Paleocene to early Eocene (59 Ma, 95% HPD: 53-66 Ma), and rapidly diversified, converting from root parasitic to aerial parasitic trophic mode ca. 50 Ma during the Eocene climatic optimum. Subsequently, Loranthaceae were inferred to be widespread in Australasia and South America but absent in Africa. The African and European members were derived from Asiatic lineages. The burst of diversification of Loranthaceae occurred during a climatic optimum period that coincides with the dominance of tropical forests in the world. This also corresponds to the trophic mode conversion of Loranthaceae and rapid radiation of many bird families - important agents for long-distance dispersal in the Cenozoic.}, } @article {pmid29550364, year = {2018}, author = {Kontarakis, Z and Rossi, A and Ramas, S and Dellinger, MT and Stainier, DYR}, title = {Mir-126 is a conserved modulator of lymphatic development.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {120-130}, doi = {10.1016/j.ydbio.2018.03.006}, pmid = {29550364}, issn = {1095-564X}, mesh = {Animals ; Animals, Genetically Modified ; Blotting, Western ; Cell Culture Techniques ; Endothelial Cells/metabolism ; Genotyping Techniques ; Humans ; Lymphangiogenesis/*genetics ; Lymphatic Vessels/embryology/metabolism ; Mice ; MicroRNAs/*genetics ; Signal Transduction/genetics ; Vascular Endothelial Growth Factor A/metabolism ; Zebrafish ; Zebrafish Proteins/genetics ; }, abstract = {Organ homeostasis relies upon cellular and molecular processes that restore tissue structure and function in a timely fashion. Lymphatic vessels help maintain fluid equilibrium by returning interstitial fluid that evades venous uptake back to the circulation. Despite its important role in tissue homeostasis, cancer metastasis, and close developmental origins with the blood vasculature, the number of molecular players known to control lymphatic system development is relatively low. Here we show, using genetic approaches in zebrafish and mice, that the endothelial specific microRNA mir-126, previously implicated in vascular integrity, regulates lymphatic development. In zebrafish, in contrast to mir-126 morphants, double mutants (mir-126a-/-; mir-126b-/-, hereafter mir-126-/-) do not exhibit defects in vascular integrity but develop lymphatic hypoplasia; mir-126-/- animals fail to develop complete trunk and facial lymphatics, display severe edema and die as larvae. Notably, following MIR-126 inhibition, human Lymphatic Endothelial Cells (hLECs) respond poorly to VEGFA and VEGFC. In this context, we identify a concomitant reduction in Vascular Endothelial Growth Factor Receptor-2 (VEGFR2) and Vascular Endothelial Growth Factor Receptor-3 (VEGFR3, also known as FLT4) expression upon MIR-126 inhibition. In vivo, we further show that flt4+/- zebrafish embryos exhibit lymphatic defects after mild miR-126 knockdown. Similarly, loss of Mir-126 in Flt4+/- mice results in embryonic edema and lethality. Thus, our results indicate that miR-126 modulation of Vegfr signaling is essential for lymphatic system development in fish and mammals.}, } @article {pmid29550363, year = {2018}, author = {Oda-Ishii, I and Abe, T and Satou, Y}, title = {Dynamics of two key maternal factors that initiate zygotic regulatory programs in ascidian embryos.}, journal = {Developmental biology}, volume = {437}, number = {1}, pages = {50-59}, doi = {10.1016/j.ydbio.2018.03.009}, pmid = {29550363}, issn = {1095-564X}, mesh = {Animals ; Blotting, Western ; Cell Division/*genetics ; Ciona intestinalis/genetics ; Embryo, Nonmammalian/metabolism ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Reverse Transcriptase Polymerase Chain Reaction ; Transcription Factors/metabolism ; Zygote/*metabolism ; beta Catenin/*metabolism ; }, abstract = {In animal embryos, transcription is repressed for a definite period of time after fertilization. In the embryo of the ascidian, Ciona intestinalis (type A; or Ciona robusta), transcription of regulatory genes is repressed before the 8- or 16-cell stages. This initial transcriptional quiescence is important to enable the establishment of initial differential gene expression patterns along the animal-vegetal axis by maternal factors, because the third cell division separates the animal and vegetal hemispheres into distinct blastomeres. Indeed, maternal transcription factors directly activate zygotic gene expression by the 16-cell stage; Tcf7/β-catenin activates genes in the vegetal hemisphere, and Gata.a activates genes in the animal hemisphere. In the present study, we revealed the dynamics of Gata.a and β-catenin, and expression profiles of their target genes precisely. β-catenin began to translocate into the nuclei at the 16-cell stage, and thus expression of β-catenin targets began at the 16-cell stage. Although Gata.a is abundantly present before the 8-cell stage, transcription of Gata.a targets was repressed at and before the 4-cell stage, and their expression began at the 8-cell stage. Transcription of the β-catenin targets may be repressed by the same mechanism in early embryos, because β-catenin targets were not expressed in 4-cell embryos treated with a GSK inhibitor, in which β-catenin translocated to the nuclei. Thus, these two maternal factors have different dynamics, which establish the pre-pattern for zygotic genetic programs in 16-cell embryos.}, } @article {pmid29550356, year = {2018}, author = {Jia, X and Dini-Andreote, F and Falcão Salles, J}, title = {Community Assembly Processes of the Microbial Rare Biosphere.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {738-747}, doi = {10.1016/j.tim.2018.02.011}, pmid = {29550356}, issn = {1878-4380}, abstract = {Our planet teems with microorganisms that often present a skewed abundance distribution in a local community, with relatively few dominant species coexisting alongside a high number of rare species. Recent studies have demonstrated that these rare taxa serve as limitless reservoirs of genetic diversity, and perform disproportionate types of functions despite their low abundances. However, relatively little is known about the mechanisms controlling rarity and the processes promoting the development of the rare biosphere. Here, we propose the use of multivariate cut-offs to estimate rare species and phylogenetic null models applied to predefined rare taxa to disentangle the relative influences of ecoevolutionary processes mediating the assembly of the rare biosphere. Importantly, the identification of the factors controlling rare species assemblages is critical for understanding the types of rarity, how the rare biosphere is established, and how rare microorganisms fluctuate over spatiotemporal scales, thus enabling prospective predictions of ecosystem responses.}, } @article {pmid29549797, year = {2018}, author = {Cai, Q and He, B and Kogel, KH and Jin, H}, title = {Cross-kingdom RNA trafficking and environmental RNAi-nature's blueprint for modern crop protection strategies.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {58-64}, doi = {10.1016/j.mib.2018.02.003}, pmid = {29549797}, issn = {1879-0364}, abstract = {In plants, small RNA (sRNA)-mediated RNA interference (RNAi) is critical for regulating host immunity against bacteria, fungi, oomycetes, viruses, and pests. Similarly, sRNAs from pathogens and pests also play an important role in modulating their virulence. Strikingly, recent evidence supports that some sRNAs can travel between interacting organisms and induce gene silencing in the counter party, a mechanism termed cross-kingdom RNAi. Exploiting this new knowledge, host-induced gene silencing (HIGS) by transgenic expression of pathogen gene-targeting double-stranded (ds)RNA has the potential to become an important disease-control method. To circumvent transgenic approaches, direct application of dsRNAs or sRNAs (environmental RNAi) onto host plants or post-harvest products leads to silencing of the target microbe/pest gene (referred to spray-induced gene silencing, SIGS) and confers efficient disease control. This review summarizes the current understanding of cross-kingdom RNA trafficking and environmental RNAi and how these findings can be developed into novel effective strategies to fight diseases caused by microbial pathogens and pests.}, } @article {pmid29549427, year = {2018}, author = {Zhang, Z and Sun, H and Chen, Y and Cao, T and Songyang, Z and Huang, J and Huang, Y}, title = {Analysis of hpf1 expression and function in early embryonic development of zebrafish.}, journal = {Development genes and evolution}, volume = {228}, number = {2}, pages = {141-147}, pmid = {29549427}, issn = {1432-041X}, support = {31401223//National Natural Science Foundation of China/International ; 81330055//National Natural Science Foundation of China/International ; 2017YFC1001901 and 2017YFC1001600//National Key R&D Program of China/International ; 2015A020212010//Guangdong Science and Technology Department Planning Project/International ; 201710010042//Zhujiang Program of Science and Technology Nova in Guangzhou/International ; 161gpy30//the Fundamental Research Funds for the Central Universities/International ; }, mesh = {Amino Acid Sequence ; Animals ; Animals, Genetically Modified/genetics/metabolism ; Carrier Proteins/genetics/*metabolism ; Embryo, Nonmammalian/cytology/*metabolism ; Embryonic Development ; *Gene Expression Regulation, Developmental ; Humans ; *Models, Animal ; Nuclear Proteins/genetics/*metabolism ; Poly (ADP-Ribose) Polymerase-1/*genetics ; Sequence Alignment ; Zebrafish/*embryology/genetics/*metabolism ; }, abstract = {About 70% of zebrafish (Danio rerio) genes are orthologues of the human's, which are of great interests, but still largely unknown for their functions. Recently, a report on human histone PARylation factor 1 (HPF1/C4orf27) showed that it is involved in DNA damage response along with poly (ADP-ribose) polymerase 1 (PARP1). However, its function in living organism remains unclear. Given that zebrafish has showed its values in modeling human diseases and physiology, we characterized a zebrafish homolog of human HPF1 by sequence alignment. We also analyzed its expression pattern during early development and among adult tissues. Furthermore, knocking down hpf1 by morpholinos affected zebrafish early development. Our work provides a novel clue for the mechanism of genome stability and early embryogenesis.}, } @article {pmid29549330, year = {2018}, author = {Turcot, V and Lu, Y and Highland, HM and Schurmann, C and Justice, AE and Fine, RS and Bradfield, JP and Esko, T and Giri, A and Graff, M and Guo, X and Hendricks, AE and Karaderi, T and Lempradl, A and Locke, AE and Mahajan, A and Marouli, E and Sivapalaratnam, S and Young, KL and Alfred, T and Feitosa, MF and Masca, NGD and Manning, AK and Medina-Gomez, C and Mudgal, P and Ng, MCY and Reiner, AP and Vedantam, S and Willems, SM and Winkler, TW and Abecasis, G and Aben, KK and Alam, DS and Alharthi, SE and Allison, M and Amouyel, P and Asselbergs, FW and Auer, PL and Balkau, B and Bang, LE and Barroso, I and Bastarache, L and Benn, M and Bergmann, S and Bielak, LF and Blüher, M and Boehnke, M and Boeing, H and Boerwinkle, E and Böger, CA and Bork-Jensen, J and Bots, ML and Bottinger, EP and Bowden, DW and Brandslund, I and Breen, G and Brilliant, MH and Broer, L and Brumat, M and Burt, AA and Butterworth, AS and Campbell, PT and Cappellani, S and Carey, DJ and Catamo, E and Caulfield, MJ and Chambers, JC and Chasman, DI and Chen, YI and Chowdhury, R and Christensen, C and Chu, AY and Cocca, M and Collins, FS and Cook, JP and Corley, J and Corominas Galbany, J and Cox, AJ and Crosslin, DS and Cuellar-Partida, G and D'Eustacchio, A and Danesh, J and Davies, G and Bakker, PIW and Groot, MCH and Mutsert, R and Deary, IJ and Dedoussis, G and Demerath, EW and Heijer, M and Hollander, AI and Ruijter, HM and Dennis, JG and Denny, JC and Di Angelantonio, E and Drenos, F and Du, M and Dubé, MP and Dunning, AM and Easton, DF and Edwards, TL and Ellinghaus, D and Ellinor, PT and Elliott, P and Evangelou, E and Farmaki, AE and Farooqi, IS and Faul, JD and Fauser, S and Feng, S and Ferrannini, E and Ferrieres, J and Florez, JC and Ford, I and Fornage, M and Franco, OH and Franke, A and Franks, PW and Friedrich, N and Frikke-Schmidt, R and Galesloot, TE and Gan, W and Gandin, I and Gasparini, P and Gibson, J and Giedraitis, V and Gjesing, AP and Gordon-Larsen, P and Gorski, M and Grabe, HJ and Grant, SFA and Grarup, N and Griffiths, HL and Grove, ML and Gudnason, V and Gustafsson, S and Haessler, J and Hakonarson, H and Hammerschlag, AR and Hansen, T and Harris, KM and Harris, TB and Hattersley, AT and Have, CT and Hayward, C and He, L and Heard-Costa, NL and Heath, AC and Heid, IM and Helgeland, Ø and Hernesniemi, J and Hewitt, AW and Holmen, OL and Hovingh, GK and Howson, JMM and Hu, Y and Huang, PL and Huffman, JE and Ikram, MA and Ingelsson, E and Jackson, AU and Jansson, JH and Jarvik, GP and Jensen, GB and Jia, Y and Johansson, S and Jørgensen, ME and Jørgensen, T and Jukema, JW and Kahali, B and Kahn, RS and Kähönen, M and Kamstrup, PR and Kanoni, S and Kaprio, J and Karaleftheri, M and Kardia, SLR and Karpe, F and Kathiresan, S and Kee, F and Kiemeney, LA and Kim, E and Kitajima, H and Komulainen, P and Kooner, JS and Kooperberg, C and Korhonen, T and Kovacs, P and Kuivaniemi, H and Kutalik, Z and Kuulasmaa, K and Kuusisto, J and Laakso, M and Lakka, TA and Lamparter, D and Lange, EM and Lange, LA and Langenberg, C and Larson, EB and Lee, NR and Lehtimäki, T and Lewis, CE and Li, H and Li, J and Li-Gao, R and Lin, H and Lin, KH and Lin, LA and Lin, X and Lind, L and Lindström, J and Linneberg, A and Liu, CT and Liu, DJ and Liu, Y and Lo, KS and Lophatananon, A and Lotery, AJ and Loukola, A and Luan, J and Lubitz, SA and Lyytikäinen, LP and Männistö, S and Marenne, G and Mazul, AL and McCarthy, MI and McKean-Cowdin, R and Medland, SE and Meidtner, K and Milani, L and Mistry, V and Mitchell, P and Mohlke, KL and Moilanen, L and Moitry, M and Montgomery, GW and Mook-Kanamori, DO and Moore, C and Mori, TA and Morris, AD and Morris, AP and Müller-Nurasyid, M and Munroe, PB and Nalls, MA and Narisu, N and Nelson, CP and Neville, M and Nielsen, SF and Nikus, K and Njølstad, PR and Nordestgaard, BG and Nyholt, DR and O'Connel, JR and O'Donoghue, ML and Olde Loohuis, LM and Ophoff, RA and Owen, KR and Packard, CJ and Padmanabhan, S and Palmer, CNA and Palmer, ND and Pasterkamp, G and Patel, AP and Pattie, A and Pedersen, O and Peissig, PL and Peloso, GM and Pennell, CE and Perola, M and Perry, JA and Perry, JRB and Pers, TH and Person, TN and Peters, A and Petersen, ERB and Peyser, PA and Pirie, A and Polasek, O and Polderman, TJ and Puolijoki, H and Raitakari, OT and Rasheed, A and Rauramaa, R and Reilly, DF and Renström, F and Rheinberger, M and Ridker, PM and Rioux, JD and Rivas, MA and Roberts, DJ and Robertson, NR and Robino, A and Rolandsson, O and Rudan, I and Ruth, KS and Saleheen, D and Salomaa, V and Samani, NJ and Sapkota, Y and Sattar, N and Schoen, RE and Schreiner, PJ and Schulze, MB and Scott, RA and Segura-Lepe, MP and Shah, SH and Sheu, WH and Sim, X and Slater, AJ and Small, KS and Smith, AV and Southam, L and Spector, TD and Speliotes, EK and Starr, JM and Stefansson, K and Steinthorsdottir, V and Stirrups, KE and Strauch, K and Stringham, HM and Stumvoll, M and Sun, L and Surendran, P and Swift, AJ and Tada, H and Tansey, KE and Tardif, JC and Taylor, KD and Teumer, A and Thompson, DJ and Thorleifsson, G and Thorsteinsdottir, U and Thuesen, BH and Tönjes, A and Tromp, G and Trompet, S and Tsafantakis, E and Tuomilehto, J and Tybjaerg-Hansen, A and Tyrer, JP and Uher, R and Uitterlinden, AG and Uusitupa, M and Laan, SW and Duijn, CM and Leeuwen, N and van Setten, J and Vanhala, M and Varbo, A and Varga, TV and Varma, R and Velez Edwards, DR and Vermeulen, SH and Veronesi, G and Vestergaard, H and Vitart, V and Vogt, TF and Völker, U and Vuckovic, D and Wagenknecht, LE and Walker, M and Wallentin, L and Wang, F and Wang, CA and Wang, S and Wang, Y and Ware, EB and Wareham, NJ and Warren, HR and Waterworth, DM and Wessel, J and White, HD and Willer, CJ and Wilson, JG and Witte, DR and Wood, AR and Wu, Y and Yaghootkar, H and Yao, J and Yao, P and Yerges-Armstrong, LM and Young, R and Zeggini, E and Zhan, X and Zhang, W and Zhao, JH and Zhao, W and Zhao, W and Zhou, W and Zondervan, KT and Rotter, JI and Pospisilik, JA and Rivadeneira, F and Borecki, IB and Deloukas, P and Frayling, TM and Lettre, G and North, KE and Lindgren, CM and Hirschhorn, JN and Loos, RJF and , and , and , and , and , and , and , and , and , and , and , }, title = {Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {766-767}, doi = {10.1038/s41588-018-0082-3}, pmid = {29549330}, issn = {1546-1718}, support = {T32 CA009156/CA/NCI NIH HHS/United States ; }, abstract = {In the version of this article originally published, one of the two authors with the name Wei Zhao was omitted from the author list and the affiliations for both authors were assigned to the single Wei Zhao in the author list. In addition, the ORCID for Wei Zhao (Department of Biostatistics and Epidemiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA) was incorrectly assigned to author Wei Zhou. The errors have been corrected in the HTML and PDF versions of the article.}, } @article {pmid29549329, year = {2018}, author = {Turcot, V and Lu, Y and Highland, HM and Schurmann, C and Justice, AE and Fine, RS and Bradfield, JP and Esko, T and Giri, A and Graff, M and Guo, X and Hendricks, AE and Karaderi, T and Lempradl, A and Locke, AE and Mahajan, A and Marouli, E and Sivapalaratnam, S and Young, KL and Alfred, T and Feitosa, MF and Masca, NGD and Manning, AK and Medina-Gomez, C and Mudgal, P and Ng, MCY and Reiner, AP and Vedantam, S and Willems, SM and Winkler, TW and Abecasis, G and Aben, KK and Alam, DS and Alharthi, SE and Allison, M and Amouyel, P and Asselbergs, FW and Auer, PL and Balkau, B and Bang, LE and Barroso, I and Bastarache, L and Benn, M and Bergmann, S and Bielak, LF and Blüher, M and Boehnke, M and Boeing, H and Boerwinkle, E and Böger, CA and Bork-Jensen, J and Bots, ML and Bottinger, EP and Bowden, DW and Brandslund, I and Breen, G and Brilliant, MH and Broer, L and Brumat, M and Burt, AA and Butterworth, AS and Campbell, PT and Cappellani, S and Carey, DJ and Catamo, E and Caulfield, MJ and Chambers, JC and Chasman, DI and Chen, YI and Chowdhury, R and Christensen, C and Chu, AY and Cocca, M and Collins, FS and Cook, JP and Corley, J and Corominas Galbany, J and Cox, AJ and Crosslin, DS and Cuellar-Partida, G and D'Eustacchio, A and Danesh, J and Davies, G and Bakker, PIW and Groot, MCH and Mutsert, R and Deary, IJ and Dedoussis, G and Demerath, EW and Heijer, M and Hollander, AI and Ruijter, HM and Dennis, JG and Denny, JC and Angelantonio, E and Drenos, F and Du, M and Dubé, MP and Dunning, AM and Easton, DF and Edwards, TL and Ellinghaus, D and Ellinor, PT and Elliott, P and Evangelou, E and Farmaki, AE and Farooqi, IS and Faul, JD and Fauser, S and Feng, S and Ferrannini, E and Ferrieres, J and Florez, JC and Ford, I and Fornage, M and Franco, OH and Franke, A and Franks, PW and Friedrich, N and Frikke-Schmidt, R and Galesloot, TE and Gan, W and Gandin, I and Gasparini, P and Gibson, J and Giedraitis, V and Gjesing, AP and Gordon-Larsen, P and Gorski, M and Grabe, HJ and Grant, SFA and Grarup, N and Griffiths, HL and Grove, ML and Gudnason, V and Gustafsson, S and Haessler, J and Hakonarson, H and Hammerschlag, AR and Hansen, T and Harris, KM and Harris, TB and Hattersley, AT and Have, CT and Hayward, C and He, L and Heard-Costa, NL and Heath, AC and Heid, IM and Helgeland, Ø and Hernesniemi, J and Hewitt, AW and Holmen, OL and Hovingh, GK and Howson, JMM and Hu, Y and Huang, PL and Huffman, JE and Ikram, MA and Ingelsson, E and Jackson, AU and Jansson, JH and Jarvik, GP and Jensen, GB and Jia, Y and Johansson, S and Jørgensen, ME and Jørgensen, T and Jukema, JW and Kahali, B and Kahn, RS and Kähönen, M and Kamstrup, PR and Kanoni, S and Kaprio, J and Karaleftheri, M and Kardia, SLR and Karpe, F and Kathiresan, S and Kee, F and Kiemeney, LA and Kim, E and Kitajima, H and Komulainen, P and Kooner, JS and Kooperberg, C and Korhonen, T and Kovacs, P and Kuivaniemi, H and Kutalik, Z and Kuulasmaa, K and Kuusisto, J and Laakso, M and Lakka, TA and Lamparter, D and Lange, EM and Lange, LA and Langenberg, C and Larson, EB and Lee, NR and Lehtimäki, T and Lewis, CE and Li, H and Li, J and Li-Gao, R and Lin, H and Lin, KH and Lin, LA and Lin, X and Lind, L and Lindström, J and Linneberg, A and Liu, CT and Liu, DJ and Liu, Y and Lo, KS and Lophatananon, A and Lotery, AJ and Loukola, A and Luan, J and Lubitz, SA and Lyytikäinen, LP and Männistö, S and Marenne, G and Mazul, AL and McCarthy, MI and McKean-Cowdin, R and Medland, SE and Meidtner, K and Milani, L and Mistry, V and Mitchell, P and Mohlke, KL and Moilanen, L and Moitry, M and Montgomery, GW and Mook-Kanamori, DO and Moore, C and Mori, TA and Morris, AD and Morris, AP and Müller-Nurasyid, M and Munroe, PB and Nalls, MA and Narisu, N and Nelson, CP and Neville, M and Nielsen, SF and Nikus, K and Njølstad, PR and Nordestgaard, BG and Nyholt, DR and O'Connel, JR and O'Donoghue, ML and Olde Loohuis, LM and Ophoff, RA and Owen, KR and Packard, CJ and Padmanabhan, S and Palmer, CNA and Palmer, ND and Pasterkamp, G and Patel, AP and Pattie, A and Pedersen, O and Peissig, PL and Peloso, GM and Pennell, CE and Perola, M and Perry, JA and Perry, JRB and Pers, TH and Person, TN and Peters, A and Petersen, ERB and Peyser, PA and Pirie, A and Polasek, O and Polderman, TJ and Puolijoki, H and Raitakari, OT and Rasheed, A and Rauramaa, R and Reilly, DF and Renström, F and Rheinberger, M and Ridker, PM and Rioux, JD and Rivas, MA and Roberts, DJ and Robertson, NR and Robino, A and Rolandsson, O and Rudan, I and Ruth, KS and Saleheen, D and Salomaa, V and Samani, NJ and Sapkota, Y and Sattar, N and Schoen, RE and Schreiner, PJ and Schulze, MB and Scott, RA and Segura-Lepe, MP and Shah, SH and Sheu, WH and Sim, X and Slater, AJ and Small, KS and Smith, AV and Southam, L and Spector, TD and Speliotes, EK and Starr, JM and Stefansson, K and Steinthorsdottir, V and Stirrups, KE and Strauch, K and Stringham, HM and Stumvoll, M and Sun, L and Surendran, P and Swift, AJ and Tada, H and Tansey, KE and Tardif, JC and Taylor, KD and Teumer, A and Thompson, DJ and Thorleifsson, G and Thorsteinsdottir, U and Thuesen, BH and Tönjes, A and Tromp, G and Trompet, S and Tsafantakis, E and Tuomilehto, J and Tybjaerg-Hansen, A and Tyrer, JP and Uher, R and Uitterlinden, AG and Uusitupa, M and Laan, SW and Duijn, CM and Leeuwen, N and van Setten, J and Vanhala, M and Varbo, A and Varga, TV and Varma, R and Velez Edwards, DR and Vermeulen, SH and Veronesi, G and Vestergaard, H and Vitart, V and Vogt, TF and Völker, U and Vuckovic, D and Wagenknecht, LE and Walker, M and Wallentin, L and Wang, F and Wang, CA and Wang, S and Wang, Y and Ware, EB and Wareham, NJ and Warren, HR and Waterworth, DM and Wessel, J and White, HD and Willer, CJ and Wilson, JG and Witte, DR and Wood, AR and Wu, Y and Yaghootkar, H and Yao, J and Yao, P and Yerges-Armstrong, LM and Young, R and Zeggini, E and Zhan, X and Zhang, W and Zhao, JH and Zhao, W and Zhou, W and Zondervan, KT and Rotter, JI and Pospisilik, JA and Rivadeneira, F and Borecki, IB and Deloukas, P and Frayling, TM and Lettre, G and North, KE and Lindgren, CM and Hirschhorn, JN and Loos, RJF and , and , and , and , and , and , and , and , and , and , and , }, title = {Publisher Correction: Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {765-766}, doi = {10.1038/s41588-018-0050-y}, pmid = {29549329}, issn = {1546-1718}, support = {MR/L01341X/1//Medical Research Council/United Kingdom ; MR/L01632X/1//Medical Research Council/United Kingdom ; }, abstract = {In the published version of this paper, the name of author Emanuele Di Angelantonio was misspelled. This error has now been corrected in the HTML and PDF versions of the article.}, } @article {pmid29549155, year = {2018}, author = {Del Junco, C and Tociu, L and Vaikuntanathan, S}, title = {Energy dissipation and fluctuations in a driven liquid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3569-3574}, pmid = {29549155}, issn = {1091-6490}, abstract = {Minimal models of active and driven particles have recently been used to elucidate many properties of nonequilibrium systems. However, the relation between energy consumption and changes in the structure and transport properties of these nonequilibrium materials remains to be explored. We explore this relation in a minimal model of a driven liquid that settles into a time periodic steady state. Using concepts from stochastic thermodynamics and liquid state theories, we show how the work performed on the system by various nonconservative, time-dependent forces-this quantifies a violation of time reversal symmetry-modifies the structural, transport, and phase transition properties of the driven liquid.}, } @article {pmid29549154, year = {2018}, author = {Malhi, Y}, title = {Ancient deforestation in the green heart of Africa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3202-3204}, pmid = {29549154}, issn = {1091-6490}, mesh = {Africa ; *Conservation of Natural Resources ; *Trees ; }, } @article {pmid29549153, year = {2018}, author = {Merino, F and Raunser, S}, title = {The complex simplicity of the bacterial cytoskeleton.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3205-3206}, pmid = {29549153}, issn = {1091-6490}, mesh = {Actins ; *Bacteria ; Bacterial Proteins ; *Cytoskeleton ; Microtubules ; }, } @article {pmid29549152, year = {2018}, author = {Kannan, RM}, title = {Toward new design principles for superior gene silencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3200-3201}, pmid = {29549152}, issn = {1091-6490}, mesh = {*Gene Silencing ; *Genetic Vectors ; RNA, Small Interfering ; }, } @article {pmid29549151, year = {2018}, author = {Rees, MJ}, title = {Donald Lynden-Bell (1935-2018).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3510-3511}, doi = {10.1073/pnas.1803355115}, pmid = {29549151}, issn = {1091-6490}, } @article {pmid29548980, year = {2018}, author = {Yang, T and Lu, LM and Wang, W and Li, JH and Manchester, SR and Wen, J and Chen, ZD}, title = {Boreotropical range expansion and long-distance dispersal explain two amphi-Pacific tropical disjunctions in Sabiaceae.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {181-191}, doi = {10.1016/j.ympev.2018.03.005}, pmid = {29548980}, issn = {1095-9513}, mesh = {Bayes Theorem ; Biodiversity ; Fossils ; Geography ; Magnoliopsida/anatomy & histology/*physiology ; Pacific Ocean ; Phylogeny ; Seed Dispersal/*physiology ; Time Factors ; *Tropical Climate ; }, abstract = {Sabiaceae comprises three genera and ca. 80 species with an amphi-Pacific tropical disjunct distribution. It has been unclear whether the family is monophyletic, where the family belongs within the angiosperm phylogeny, and when and how is present-day disjunct distribution originated. To address these questions, we conducted a phylogenetic analysis of Sabiaceae with comprehensive sampling of the family and basal eudicots using six chloroplast DNA loci (atpB, rbcL, matK, ndhF, atpB-rbcL and trnL-trnF). Our results support the monophyly of Sabiaceae s. l. that includes three genera: Meliosma Blume, Ophiocaryon Endl. and Sabia Colebr. The placement of Sabiaceae as sister to Proteales receives moderate bootstrap support, and is corroborated by various alternative hypothesis tests. Within Sabiaceae, Ophiocaryon and Sabia were resolved as strongly supported clades, whereas Meliosma was paraphyletic with Ophiocaryon nested within it. The biogeographically disjunct accessions of Meliosma alba (which is alternatively known as Kingsboroughia alba (Schltdl.) Liebm.) sampled from southwestern China and Mexico form a monophyletic group. Molecular dating and ancestral area reconstruction suggest a Eurasian origin of Sabiaceae in the late Cretaceous and a boreotropical range expansion during Paleogene. Southward migrations were inferred from continental Eurasia to the Malesian region in Sabia and in the Asian Meliosma, and from Central America to South America in the Neotropical clade of Meliosma in response to climatic cooling after the late Miocene. A long distance dispersal from Central America to tropical Asia was suggested during the time at the Neogene and Quaternary boundary in Meliosma alba (now recognized as Kingsboroughia alba). Our results also support the recognition of Kingsboroughia Liebm. as a distinct genus to maintain the monophyly of each of the genera: Meliosma, Ophiocaryon and Sabia. Kingsboroughia along with Meliosma and Ophiocaryon constitutes the subfamily Meliosmoideae Mast., while Sabia is the sole genus of Sabioideae Y.W. Law & Y.F. Wu.}, } @article {pmid29548944, year = {2018}, author = {Watanabe, Y and Sakuma, C and Yaginuma, H}, title = {Dispersing movement of tangential neuronal migration in superficial layers of the developing chick optic tectum.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {131-139}, doi = {10.1016/j.ydbio.2018.03.010}, pmid = {29548944}, issn = {1095-564X}, mesh = {Animals ; Cell Culture Techniques ; Cell Movement/*physiology ; Chickens ; Electroporation ; Neurogenesis/*physiology ; Neurons/physiology ; Superior Colliculi/*embryology ; Time-Lapse Imaging ; }, abstract = {During embryonic brain development, groups of particular neuronal cells migrate tangentially to participate in the formation of a laminated structure. Two distinct types of tangential migration in the middle and superficial layers have been reported in the development of the avian optic tectum. Here we show the dynamics of tangential cell movement in superficial layers of developing chick optic tectum. Confocal time-lapse microscopy in organotypic slice cultures and flat-mount cultures revealed that vigorous cell migration continued during E6.5-E13.5, where horizontally elongated superficial cells spread out tangentially. Motile cells exhibited exploratory behavior in reforming the branched leading processes to determine their pathway, and intersected with each other for dispersion. At the tectal peripheral border, the cells retraced or turned around to avoid protruding over the border. The tangentially migrating cells were eventually distributed in the outer stratum griseum et fibrosum superficiale and differentiated into neurons of various morphologies. These results revealed the cellular dynamics for widespread neuronal distribution in the superficial layers of the developing optic tectum, which underline a mode of novel tangential neuronal migration in the developing brain.}, } @article {pmid29548943, year = {2018}, author = {Kidwell, CU and Su, CY and Hibi, M and Moens, CB}, title = {Multiple zebrafish atoh1 genes specify a diversity of neuronal types in the zebrafish cerebellum.}, journal = {Developmental biology}, volume = {438}, number = {1}, pages = {44-56}, pmid = {29548943}, issn = {1095-564X}, support = {R01 NS082567/NS/NINDS NIH HHS/United States ; T32 HD007183/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/*metabolism ; Cell Differentiation/genetics ; Cell Movement/genetics ; Cerebellum/*embryology/metabolism ; Fluorescent Antibody Technique ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Neurogenesis/*genetics ; Neurons/metabolism ; Signal Transduction ; Zebrafish/embryology/genetics ; Zebrafish Proteins/*genetics/metabolism ; }, abstract = {A single Atoh1 basic-helix-loop-helix transcription factor specifies multiple neuron types in the mammalian cerebellum and anterior hindbrain. The zebrafish genome encodes three paralagous atoh1 genes whose functions in cerebellum and anterior hindbrain development we explore here. With use of a transgenic reporter, we report that zebrafish atoh1c-expressing cells are organized in two distinct domains that are separated both by space and developmental time. An early isthmic expression domain gives rise to an extracerebellar population in rhombomere 1 and an upper rhombic lip domain gives rise to granule cell progenitors that migrate to populate all four granule cell territories of the fish cerebellum. Using genetic mutants we find that of the three zebrafish atoh1 paralogs, atoh1c and atoh1a are required for the full complement of granule neurons. Surprisingly, the two genes are expressed in non-overlapping granule cell progenitor populations, indicating that fish use duplicate atoh1 genes to generate granule cell diversity that is not detected in mammals. Finally, live imaging of granule cell migration in wildtype and atoh1c mutant embryos reveals that while atoh1c is not required for granule cell specification per se, it is required for granule cells to delaminate and migrate away from the rhombic lip.}, } @article {pmid29548942, year = {2018}, author = {Elliott, KH and Brugmann, SA}, title = {Sending mixed signals: Cilia-dependent signaling during development and disease.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29548942}, issn = {1095-564X}, support = {R01 DE023804/DE/NIDCR NIH HHS/United States ; R35 DE027557/DE/NIDCR NIH HHS/United States ; }, abstract = {Molecular signals are the guiding force of development, imparting direction upon cells to divide, migrate, differentiate, etc. The mechanisms by which a cell can receive and transduce these signals into measurable actions remains a 'black box' in developmental biology. Primary cilia are ubiquitous, microtubule-based organelles that dynamically extend from a cell to receive and process molecular and mechanical signaling cues. In the last decade, this organelle has become increasingly intriguing to the research community due to its ability to act as a cellular antenna, receive and transduce molecular stimuli, and initiate a cellular response. In this review, we discuss the structure of primary cilia, emphasizing how the ciliary components contribute to the transduction of signaling pathways. Furthermore, we address how the cilium integrates these signals and conveys them into cellular processes such as proliferation, migration and tissue patterning. Gaining a deeper understanding of the mechanisms used by primary cilia to receive and integrate molecular signals is essential, as it opens the door for the identification of therapeutic targets within the cilium that could alleviate pathological conditions brought on by aberrant molecular signaling.}, } @article {pmid29548888, year = {2018}, author = {Keesing, F and Ostfeld, RS}, title = {The Tick Project: Testing Environmental Methods of Preventing Tick-borne Diseases.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {447-450}, doi = {10.1016/j.pt.2018.02.008}, pmid = {29548888}, issn = {1471-5007}, mesh = {Animals ; Humans ; New York ; *Pest Control, Biological/standards ; *Tick Control/standards ; Tick-Borne Diseases/*prevention & control ; }, abstract = {Prevention of tick-borne diseases in humans is challenging. To date, no prevention strategies have been shown to be consistently effective. Here, we describe the design of a new large-scale study, involving hundreds of households in Dutchess County, New York, testing whether environmental interventions, applied intensively and over 4 years, can prevent human cases.}, } @article {pmid29548832, year = {2018}, author = {Tsatsaronis, JA and Franch-Arroyo, S and Resch, U and Charpentier, E}, title = {Extracellular Vesicle RNA: A Universal Mediator of Microbial Communication?.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {401-410}, doi = {10.1016/j.tim.2018.02.009}, pmid = {29548832}, issn = {1878-4380}, mesh = {Archaea/physiology ; Cell Communication/*physiology ; Eukaryota/physiology ; Extracellular Vesicles/*metabolism ; Gene Expression ; Gene Silencing ; Immunity, Innate ; Prokaryotic Cells/physiology ; RNA/*metabolism ; }, abstract = {Both extracellular RNAs and extracellular vesicles (EVs) have recently garnered attention as novel mediators of intercellular communication in eukaryotes and prokaryotes alike. EVs not only permit export of RNA, but also facilitate delivery and trans-kingdom exchange of these and other biomolecules, for instance between microbes and their hosts. In this Opinion article, we propose that EV-mediated export of RNA represents a universal mechanism for interkingdom and intrakingdom communication that is conserved among bacterial, archaeal, and eukaryotic microbes. We speculate how microbes might use EV RNA to influence target cell gene expression or manipulate host immune responses.}, } @article {pmid29548284, year = {2018}, author = {Xiang, X and Liu, H}, title = {IDPM: an online database for ion distribution in protein molecules.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {102}, pmid = {29548284}, issn = {1471-2105}, support = {11575021, U1530401, U1430237//National Natural Science Foundation of China/International ; }, mesh = {Amino Acids/chemistry ; Binding Sites ; *Databases, Protein ; *Internet ; Ions/*chemistry ; Probability ; Proteins/*chemistry ; }, abstract = {BACKGROUND: Interactions between ions and proteins have been extensively studied, yet most of the studies focus on the ion binding site. The binding mechanism for many ion binding sites can be clearly described from high resolution structures. Although knowledge accumulated on a case-by-case basis is valuable, it is also important to study the ion-protein interaction statistically. From experimentally determined structures, it is possible to examine the ion distribution around each amino acid. Such distributions can reveal relation between ions and amino acids, so it is desirable to carry out a systematic survey of 'ion-amino acid' pairing interaction and share the information with a publicly available database.

RESULTS: The survey in the Protein Data Bank (PDB) revealed that approximately 40% of molecules records contain at least one ion. To reduce the bias resulted from protein redundancy, the statistics were extracted from a non-redundant dataset by excluding the proteins with similar sequences. Based on the structures of protein molecules and the location of ions, the statistical distributions of ions around each proteinogenic amino acid type were investigated and further summarized in a database. To systematically quantify the interactions between ions and each amino acid, the positions of ions were mapped to the coordinate system centered at each neighboring amino acid. It was found that the distribution of ions follows the expected rules governed by the physicochemical interactions in general. Large variations were observed, reflecting the preference in 'ion-amino acid' interactions. The analysis program is written in the Python programming language. The statistical results and program are available from the online database: ion distribution in protein molecules (IDPM) at http://liulab.csrc.ac.cn/idpm/ .

CONCLUSION: The spatial distribution of ions around amino acids is documented and analyzed. The statistics can be useful for identifying ion types for a given site in biomolecules, and can be potentially used in ion position prediction for given structures.}, } @article {pmid29548279, year = {2018}, author = {Kovac, T and Haber, T and Reeth, FV and Hens, N}, title = {Heterogeneous computing for epidemiological model fitting and simulation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {101}, pmid = {29548279}, issn = {1471-2105}, support = {682540//H2020 European Research Council/International ; }, mesh = {Algorithms ; Communicable Diseases/epidemiology ; Computer Graphics ; *Computer Simulation ; Disease Susceptibility ; *Epidemics ; *Models, Biological ; }, abstract = {BACKGROUND: Over the last years, substantial effort has been put into enhancing our arsenal in fighting epidemics from both technological and theoretical perspectives with scientists from different fields teaming up for rapid assessment of potentially urgent situations. This paper focusses on the computational aspects of infectious disease models and applies commonly available graphics processing units (GPUs) for the simulation of these models. However, fully utilizing the resources of both CPUs and GPUs requires a carefully balanced heterogeneous approach.

RESULTS: The contribution of this paper is twofold. First, an efficient GPU implementation for evaluating a small-scale ODE model; here, the basic S(usceptible)-I(nfected)-R(ecovered) model, is discussed. Second, an asynchronous particle swarm optimization (PSO) implementation is proposed where batches of particles are sent asynchronously from the host (CPU) to the GPU for evaluation. The ultimate goal is to infer model parameters that enable the model to correctly describe observed data. The particles of the PSO algorithm are candidate parameters of the model; finding the right one is a matter of optimizing the likelihood function which quantifies how well the model describes the observed data. By employing a heterogeneous approach, in which both CPU and GPU are kept busy with useful work, speedups of 10 to 12 times can be achieved on a moderate machine with a high-end consumer GPU as compared to a high-end system with 32 CPU cores.

CONCLUSIONS: Utilizing GPUs for parameter inference can bring considerable increases in performance using average host systems with high-end consumer GPUs. Future studies should evaluate the benefit of using newer CPU and GPU architectures as well as applying this method to more complex epidemiological scenarios.}, } @article {pmid29548278, year = {2018}, author = {Yan, EV and Beutel, RG and Lawrence, JF}, title = {Whirling in the late Permian: ancestral Gyrinidae show early radiation of beetles before Permian-Triassic mass extinction.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {33}, pmid = {29548278}, issn = {1471-2148}, support = {16-04-01498//Russian Foundation for Basic Research/International ; 642241//Marie Sklodowska-Curie grant/International ; BE 1789/13-1//DFG/International ; }, mesh = {Animals ; *Biological Evolution ; Coleoptera/anatomy & histology/*physiology ; *Extinction, Biological ; *Fossils ; Paleontology ; Phylogeny ; Siberia ; Time Factors ; }, abstract = {BACKGROUND: Gyrinidae are a charismatic group of highly specialized beetles, adapted for a unique lifestyle of swimming on the water surface. They prey on drowning insects and other small arthropods caught in the surface film. Studies based on morphological and molecular data suggest that gyrinids were the first branch splitting off in Adephaga, the second largest suborder of beetles. Despite its basal position within this lineage and a very peculiar morphology, earliest Gyrinidae were recorded not earlier than from the Upper Triassic.

RESULTS: Tunguskagyrus. with the single species Tunguskagyrus planus is described from Late Permian deposits of the Anakit area in Middle Siberia. The genus is assigned to the stemgroup of Gyrinidae, thus shifting back the minimum age of this taxon considerably: Tunguskagyrus demonstrates 250 million years of evolutionary stability for a very specialized lifestyle, with a number of key apomorphies characteristic for these epineuston predators and scavengers, but also with some preserved ancestral features not found in extant members of the family. It also implies that major splitting events in this suborder and in crown group Coleoptera had already occurred in the Permian. Gyrinidae and especially aquatic groups of Dytiscoidea flourished in the Mesozoic (for example Coptoclavidae and Dytiscidae) and most survive until the present day, despite the dramatic "Great Dying" - Permian-Triassic mass extinction, which took place shortly (in geological terms) after the time when Tunguskagyrus lived.

CONCLUSIONS: Tunguskagyrus confirms a Permian origin of Adephaga, which was recently suggested by phylogenetic "tip-dating" analysis including both fossil and Recent gyrinids. This also confirms that main splitting events leading to the "modern" lineages of beetles took place before the Permian-Triassic mass extinction. Tunguskagyrus shows that Gyrinidae became adapted to swimming on the water surface long before Mesozoic invasions of the aquatic environment took place (Dytiscoidea). The Permian origin of Gyrinidae is consistent with a placement of this highly derived family as the sister group of all remaining adephagan groups, as suggested based on morphological features of larvae and adults and recent analyses of molecular data.}, } @article {pmid29548277, year = {2018}, author = {Engelbrechtsen, L and Mahendran, Y and Jonsson, A and Gjesing, AP and Weeke, PE and Jørgensen, ME and Færch, K and Witte, DR and Holst, JJ and Jørgensen, T and Grarup, N and Pedersen, O and Vestergaard, H and Torekov, S and Kanters, JK and Hansen, T}, title = {Common variants in the hERG (KCNH2) voltage-gated potassium channel are associated with altered fasting and glucose-stimulated plasma incretin and glucagon responses.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {15}, pmid = {29548277}, issn = {1471-2156}, abstract = {BACKGROUND: Patients with long QT syndrome due to rare loss-of-function mutations in the human ether-á-go-go-related gene (hERG) have prolonged QT interval, risk of arrhythmias, increased secretion of insulin and incretins and impaired glucagon response to hypoglycemia. This is caused by a dysfunctional Kv11.1 voltage-gated potassium channel. Based on these findings in patients with rare variants in hERG, we hypothesized that common variants in hERG may also lead to alterations in glucose homeostasis. Subsequently, we aimed to evaluate the effect of two common gain-of-function variants in hERG (rs36210421 and rs1805123) on QT interval and plasma levels of glucagon-like peptide-1 (GLP-1), glucose-dependent insulinotropic polypeptide (GIP), insulin and glucagon during an oral glucose tolerance test (OGTT). We used two population-based cohorts for evaluation of the effect of common variants in hERG on QT-interval and circulation levels of incretins, insulin and glucagon. The Danish population-based Inter99 cohort (n = 5895) was used to assess the effect of common variants on QT-interval. The Danish ADDITION-PRO cohort was used (n = 1329) to study genetic associations with levels of GLP-1, GIP, insulin and glucagon during an OGTT.

RESULTS: Carriers of either the minor A-allele of rs36210421 or the minor G-allele of rs1805123 had ~ 2 ms shorter QT interval per risk allele (p = 0.025 and p = 1.9 × 10- 7). Additionally, both variants were associated with alterations in pancreatic and gut hormone release among carriers. The minor A- allele of rs36210421 was associated with increased GLP-1 and decreased GIP response to oral glucose stimulation, whereas the minor G-allele of rs1805123 is associated with decreased fasting plasma insulin and glucagon release. A genetic risk score combining the two gene variants revealed reductions in glucose-stimulated GIP, as well as suppressed glucagon response to increased glucose levels during an OGTT.

CONCLUSIONS: Two common missense polymorphisms of the Kv11.1 voltage-gated hERG potassium channel are associated with alterations in circulating levels of GIP and glucagon, suggesting that hERG potassium channels play a role in fasting and glucose-stimulated release of GIP and glucagon.

TRIAL REGISTRATION: ClinicalTrials.gov (NCT00289237). Trial retrospectively registered at February 9, 2006. Studies were approved by the Ethical Committee of the Central Denmark Region (journal no. 20080229) and by the Copenhagen County Ethical Committee (KA 98155).}, } @article {pmid29548275, year = {2018}, author = {He, H and Yang, Q and Shen, B and Zhang, S and Peng, X}, title = {OsNOA1 functions in a threshold-dependent manner to regulate chloroplast proteins in rice at lower temperatures.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {44}, pmid = {29548275}, issn = {1471-2229}, support = {201607020006//Science and Technology Planning of Guangzhou City/ ; 31170222//National Natural Science Foundation of China/ ; }, mesh = {Chlorophyll/metabolism ; Chloroplasts/genetics/*metabolism ; Gene Expression Regulation, Plant/genetics/physiology ; Oryza/genetics/*metabolism ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified/genetics/metabolism ; Proteomics/methods ; Ribulose-Bisphosphate Carboxylase/metabolism ; Temperature ; }, abstract = {BACKGROUND: Although decreased protein expressions have been observed in NOA1 (Nitric Oxide Associated protein 1) deficient plants, the molecular mechanisms of how NOA1 regulates protein metabolism remain poorly understood. In this study, we have used a global comparative proteomic approach for both OsNOA1 suppression and overexpression transgenic lines under two different temperatures, in combination with physiological and biochemical analyses to explore the regulatory mechanisms of OsNOA1 in rice.

RESULTS: In OsNOA1-silenced or highly overexpressed rice, considerably different expression patterns of both chlorophyll and Rubisco as well as distinct phenotypes were observed between the growth temperatures at 22 °C and 30 °C. These observations led us to hypothesize there appears a narrow abundance threshold for OsNOA1 to function properly at lower temperatures, while higher temperatures seem to partially compensate for the changes of OsNOA1 abundance. Quantitative proteomic analyses revealed higher temperatures could restore 90% of the suppressed proteins to normal levels, whereas almost all of the remaining suppressed proteins were chloroplast ribosomal proteins. Additionally, our data showed 90% of the suppressed proteins in both types of transgenic plants at lower temperatures were located in the chloroplast, suggesting a primary effect of OsNOA1 on chloroplast proteins. Transcript analyses, along with in vitro pull-down experiments further demonstrated OsNOA1 is associated with the function of chloroplast ribosomes.

CONCLUSIONS: Our results suggest OsNOA1 functions in a threshold-dependent manner for regulation of chloroplast proteins at lower temperatures, which may be mediated by interactions between OsNOA1 and chloroplast ribosomes.}, } @article {pmid29547971, year = {2018}, author = {Micoli, F and Costantino, P and Adamo, R}, title = {Potential targets for next generation antimicrobial glycoconjugate vaccines.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {388-423}, pmid = {29547971}, issn = {1574-6976}, mesh = {Bacterial Vaccines/*immunology ; Glycoconjugates/*immunology ; Humans ; Membrane Proteins/immunology ; Vaccination/trends ; }, abstract = {Cell surface carbohydrates have been proven optimal targets for vaccine development. Conjugation of polysaccharides to a carrier protein triggers a T-cell-dependent immune response to the glycan moiety. Licensed glycoconjugate vaccines are produced by chemical conjugation of capsular polysaccharides to prevent meningitis caused by meningococcus, pneumococcus and Haemophilus influenzae type b. However, other classes of carbohydrates (O-antigens, exopolysaccharides, wall/teichoic acids) represent attractive targets for developing vaccines. Recent analysis from WHO/CHO underpins alarming concern toward antibiotic-resistant bacteria, such as the so called ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) and additional pathogens such as Clostridium difficile and Group A Streptococcus. Fungal infections are also becoming increasingly invasive for immunocompromised patients or hospitalized individuals. Other emergencies could derive from bacteria which spread during environmental calamities (Vibrio cholerae) or with potential as bioterrorism weapons (Burkholderia pseudomallei and mallei, Francisella tularensis). Vaccination could aid reducing the use of broad-spectrum antibiotics and provide protection by herd immunity also to individuals who are not vaccinated.This review analyzes structural and functional differences of the polysaccharides exposed on the surface of emerging pathogenic bacteria, combined with medical need and technological feasibility of corresponding glycoconjugate vaccines.}, } @article {pmid29547927, year = {2018}, author = {Landa, M and Blain, S and Harmand, J and Monchy, S and Rapaport, A and Obernosterer, I}, title = {Major changes in the composition of a Southern Ocean bacterial community in response to diatom-derived dissolved organic matter.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy034}, pmid = {29547927}, issn = {1574-6941}, abstract = {In the Southern Ocean, natural iron fertilization in the wake of islands leads to annually occurring spring phytoplankton blooms associated with enhanced heterotrophic activity through the release of labile dissolved organic matter (DOM). The aim of this study was to investigate experimentally how diatom-derived DOM affects the composition of Southern Ocean winter water bacterial communities and to identify the most responsive taxa. A bacterial community collected in the naturally iron-fertilized region off Kerguelen Island (KEOPS2 October-November 2011) was grown onboard in continuous cultures, on winter water alone or amended with diatom-derived DOM supplied at identical DOC concentrations. 454 sequencing of 16S amplicons revealed that the two DOM sources sustained strikingly different bacterial communities, with higher relative abundances of Sulfitobacter, Colwellia and Methylophaga operational taxonomic units (OTUs) and lower relative abundances of Polaribacter, Marinobacter, NAC11-7 and SAR11 OTUs in diatom-DOM compared to winter water conditions. Using a modeling approach, we obtained growth rates for phylogenetically diverse taxa varying between 0.12 and 0.49 d-1 under carbon-limited conditions. Our results identify diatom DOM as a key factor shaping Southern Ocean winter water bacterial communities and suggest a role for niche partitioning and microbial interactions in organic matter utilization.}, } @article {pmid29547924, year = {2018}, author = {Pessi, IS and Lara, Y and Durieu, B and Maalouf, PC and Verleyen, E and Wilmotte, A}, title = {Community structure and distribution of benthic cyanobacteria in Antarctic lacustrine microbial mats.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy042}, pmid = {29547924}, issn = {1574-6941}, abstract = {The terrestrial Antarctic Realm has recently been divided into 16 Antarctic Conservation Biogeographic Regions (ACBRs) based on environmental properties and the distribution of biota. Despite their prominent role in the primary production and nutrient cycling in Antarctic lakes, cyanobacteria were only poorly represented in the biological dataset used to delineate these ACBRs. Here, we provide a first high-throughput sequencing insight into the spatial distribution of benthic cyanobacterial communities in Antarctic lakes located in four distinct, geographically distant ACBRs and covering a range of limnological conditions. Cyanobacterial community structure differed between saline and freshwater lakes. No clear bioregionalization was observed, as clusters of community similarity encompassed lakes from distinct ACBRs. Most phylotypes (77.0%) were related to cyanobacterial lineages (defined at ≥99.0% 16S rRNA gene sequence similarity) restricted to the cold biosphere, including lineages potentially endemic to Antarctica (55.4%). The latter were generally rare and restricted to a small number of lakes, while more ubiquitous phylotypes were generally abundant and present in different ACBRs. These results point to a widespread distribution of some cosmopolitan cyanobacterial phylotypes across the different Antarctic ice-free regions, but also suggest the existence of dispersal barriers both within and between Antarctica and the other continents.}, } @article {pmid29547891, year = {2018}, author = {Gazda, MA and Andrade, P and Afonso, S and Dilyte, J and Archer, JP and Lopes, RJ and Faria, R and Carneiro, M}, title = {Signatures of Selection on Standing Genetic Variation Underlie Athletic and Navigational Performance in Racing Pigeons.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1176-1189}, doi = {10.1093/molbev/msy030}, pmid = {29547891}, issn = {1537-1719}, abstract = {Racing pigeons have been selectively bred to find their way home quickly over what are often extremely long distances. This breed is of substantial commercial value and is also an excellent avian model to gain empirical insights into the evolution of traits associated with flying performance and spatial orientation. Here, we investigate the molecular basis of the superior athletic and navigational capabilities of racing pigeons using whole-genome and RNA sequencing data. We inferred multiple signatures of positive selection distributed across the genome of racing pigeons. The strongest signature overlapped the CASK gene, a gene implicated in the formation of neuromuscular junctions. However, no diagnostic alleles were found between racing pigeons and other breeds, and only a small proportion of highly differentiated variants were exclusively detected in racing pigeons. We can thus conclude that very few individual genetic changes, if any, are either strictly necessary or sufficient for superior athletics and navigation. Gene expression analysis between racing and nonracing breeds revealed modest differences in muscle (213) and brain (29). These transcripts, however, showed only slightly elevated levels of genetic differentiation between the two groups, suggesting that most differential expression is not causative but likely a consequence of alterations in regulatory networks. Our results show that the unique suite of traits that enable fast flight, long endurance, and accurate navigation in racing pigeons, do not result from few loci acting as master switches but likely from a polygenic architecture that leveraged standing genetic variation available at the onset of the breed formation.}, } @article {pmid29547886, year = {2018}, author = {Mohammed, WK and Krasnogor, N and Jakubovics, NS}, title = {Streptococcus gordonii Challisin protease is required for sensing cell--cell contact with Actinomyces oris.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy043}, pmid = {29547886}, issn = {1574-6941}, abstract = {The ability of microorganisms to regulate gene expression is thought to be critical for survival and growth during the development of polymicrobial biofilms such as dental plaque. The commensal dental plaque colonizer, Streptococcus gordonii, responds to cell--cell contact (coaggregation) with Actinomyces oris by regulating >20 genes, including those involved in arginine biosynthesis. We hypothesized that an S. gordonii extracellular protease is critical for sensing by providing amino acids that modulate gene expression. S. gordonii coaggregated strongly with A. oris in buffer, saliva or chemically defined medium (CDM). In wild-type S. gordonii, expression of arginine biosynthesis genes argC and argG increased within two hours' growth in CDM in monocultures, but not following coaggregation with A. oris. By contrast, coaggregation of A. oris with an S. gordonii mutant lacking sgc, encoding the extracellular protease Challisin, resulted in increases in argC and argG gene expression that were similar to monocultures. Genetic complementation of sgc restored the ability of S. gordonii to sense coaggregation with A. oris. Coaggregation enabled growth of S. gordonii in low/no arginine and disruption of sgc did not affect this ability. We propose that extracellular bacterial proteases may be key mediators of cell--cell contact sensing by diverse microbial species.}, } @article {pmid29547801, year = {2018}, author = {Revie, NM and Iyer, KR and Robbins, N and Cowen, LE}, title = {Antifungal drug resistance: evolution, mechanisms and impact.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {70-76}, pmid = {29547801}, issn = {1879-0364}, support = {R01 AI120958/AI/NIAID NIH HHS/United States ; R01 AI127375/AI/NIAID NIH HHS/United States ; }, abstract = {Microorganisms have a remarkable capacity to evolve resistance to antimicrobial agents, threatening the efficacy of the limited arsenal of antimicrobials and becoming a dire public health crisis. This is of particular concern for fungal pathogens, which cause devastating invasive infections with treatment options limited to only three major classes of antifungal drugs. The paucity of antifungals with clinical utility is in part due to close evolutionary relationships between these eukaryotic pathogens and their human hosts, which limits the unique targets to be exploited therapeutically. This review highlights the mechanisms by which fungal pathogens of humans evolve resistance to antifungal drugs, which provide crucial insights to enable development of novel therapeutic strategies to thwart drug resistance and combat fungal infectious disease.}, } @article {pmid29547096, year = {2018}, author = {Fang, XM and Bai, JL and Su, J and Zhao, LL and Liu, HY and Ma, BP and Zhang, YQ and Yu, LY}, title = {Glycomyces paridis sp. nov., isolated from the medicinal plant Paris polyphylla.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1578-1583}, doi = {10.1099/ijsem.0.002713}, pmid = {29547096}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Melanthiaceae/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; Plants, Medicinal/microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {Three actinomycete strains originating from the surface-sterilized roots of Paris polyphylla were characterized by using a polyphasic approach. Phylogenetic analyses based on the 16S rRNA gene sequence showed that they formed a deep, monophyletic branch in the genus Glycomyces, and were most closely related to the type strains of the species Glycomyces harbinensis and Glycomycesscopariae. Morphological and chemotaxonomic data supported the affiliation of strains CPCC 204357T, CPCC 204354 and CPCC 204355 to the genus Glycomyces. The results of physiological and biochemical tests allowed phenotypic differentiation of strains CPCC 204357T, CPCC 204354 and CPCC 204355 from their closest phylogenetic related species in the genus Glycomyces. Low levels of DNA-DNA relatedness with its closest type strains of G. harbinensis and G. scopariaeindicated that strain CPCC 204357T represent a novel species, for which the name Glycomyces paridis sp. nov. is proposed, with CPCC 204357T (=DSM 102295T=KCTC 39745T) as the type strain.}, } @article {pmid29547095, year = {2018}, author = {Zhao, JC and Cheng, J and Zhang, Q and Gao, ZW and Zhang, MY and Zhang, YX}, title = {Flavobacterium artemisiae sp. nov., isolated from the rhizosphere of Artemisia annua L. and emended descriptions of Flavobacterium compostarboris and Flavobacterium procerum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1509-1513}, doi = {10.1099/ijsem.0.002701}, pmid = {29547095}, issn = {1466-5034}, mesh = {Artemisia annua/*microbiology ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, strictly aerobic, yellow-coloured, motile by gliding and elongated rod-shaped bacterial strain, designated SYP-B1015T, was isolated from the rhizosphere of Artemisia annua L. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain SYP-B1015T belonged to the genus Flavobacterium and had highest 16S rRNA gene sequence similarity to Flavobacterium compostarboris JCM 16527T (98.1 %) and Flavobacterium procerum JCM 30113T (97.2 %). The predominant respiratory quinone for the strain was MK-6, and the major cellular fatty acids were iso-C15 : 0, iso-C15 : 0 3-OH and iso-C17 : 0 3-OH. The polar lipid profile contained phosphatidylethanolamine as a major compound. The DNA G+C content of strain SYP-B1015T was 33.5 mol%. The DNA-DNA relatedness values between strain SYP-B1015T and F. compostarboris JCM 16527T and F. procerum JCM 30113T were 56.5±0.4 and 48.9±1.2 %, respectively. Combining the data from morphological, physiological, biochemical and chemotaxonomic characterizations presented in this study, strain SYP-B1015T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium artemisiae sp. nov. is proposed. The type strain is SYP-B1015T (=CGMCC 1.16115T=KCTC 62025T).}, } @article {pmid29547093, year = {2018}, author = {Margesin, R and Zhang, DC and Albuquerque, L and Froufe, HJC and Egas, C and da Costa, MS}, title = {Lysobacter silvestris sp. nov., isolated from alpine forest soil, and reclassification of Luteimonas tolerans as Lysobacter tolerans comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1571-1577}, doi = {10.1099/ijsem.0.002710}, pmid = {29547093}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Italy ; Lysobacter/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, motile, catalase-positive and cytochrome c oxidase-positive bacterial strain, designated AM20-91T, was isolated from alpine forest soil. Phylogenetic analysis based on 16S rRNA gene sequencing showed that strain AM20-91T was related to the genus Lysobacter and had highest 16S rRNA gene sequence similarities to the type strains of Lysobacter novalis THG-PC7T (97.8 %), Luteimonas tolerans UM1T (97.7 %) and Lysobacter ximonensis XM415T (97.0 %). The strain contained ubiquinone 8 as the predominant respiratory quinone; its polar lipid profile contained phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and two unidentified aminophospholipids. The major cellular fatty acids (>10 %) were iso-C15 : 0, iso-C11 : 0 3-OH and iso-C11 : 0. The DNA G+C content was 63.35 % (draft genome sequence). The combined results of phylogenetic, phenotypic, DNA-DNA relatedness and chemotaxonomic analyses demonstrated that strain AM20-91T represents a novel species of the genus Lysobacter, for which the name Lysobacter silvestris sp. nov. is proposed. The type strain is AM20-91T (=DSM 104734T=LMG 30011). In this study, it is also proposed that Luteimonas tolerans be reclassified as member of the genus Lysobacter.}, } @article {pmid29546587, year = {2018}, author = {Liu, J and Song, Y and Lu, X and Chen, T and Guo, W and Fan, Z and Kang, X and Wang, Y and Wang, Y}, title = {Seasonal Variation Influences on Intestinal Microbiota in Rats.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {1006-1010}, pmid = {29546587}, issn = {1432-0991}, support = {81,673,801//National Natural Science Foundation of China/ ; 81,473,512//National Natural Science Foundation of China/ ; 81,173,397//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Bacteria/*classification/genetics/isolation & purification ; Base Sequence ; Colon, Ascending/*microbiology ; DNA, Bacterial/genetics ; Gastrointestinal Microbiome/*genetics ; Ileum/*microbiology ; Intestinal Mucosa/*microbiology ; Jejunum/*microbiology ; Male ; RNA, Ribosomal, 16S/genetics ; Rats ; Rats, Sprague-Dawley ; *Seasons ; Sequence Analysis, DNA ; }, abstract = {Recently, several studies have indicated that the intestinal microbiota can be regulated by the individual attributes, and even the alternation of circadian rhythm. Inspired by this, we speculated that seasonal variation might also have some effect on the intestinal microbiota. A total of 11 Sprague-Dawley male rats, weighing 250-280 g, were divided into summer group (n = 5) and winter group (n = 6). Cages were individually ventilated at 20 ± 2 °C and 45-65% relative humidity with a circadian rhythm of 12/12 h. After 1 week of adaptively feeding, mucosal contents of jejunum, terminal ileum, and ascending colon were collected and analyzed by 16S rRNA Gene Amplicon Pyrosequencing. The results showed that intestinal microbiota of rats for the same strain were affected by season change under the same feeding condition and living environment. We should take seasonal factor into account in the future experimental design based on intestinal microbiome.}, } @article {pmid29546586, year = {2018}, author = {López, SMY and Sánchez, MDM and Pastorino, GN and Franco, MEE and García, NT and Balatti, PA}, title = {Nodulation and Delayed Nodule Senescence: Strategies of Two Bradyrhizobium Japonicum Isolates with High Capacity to Fix Nitrogen.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {997-1005}, pmid = {29546586}, issn = {1432-0991}, support = {Subsidio Incentivos 2015//Universidad Nacional de La Plata/ ; Subsidio 2015//Comision de Investigaciones de la Provincia de Buenos Aires/ ; BECAR2014//Jefatura de Gabinete de Ministros de la Nacion/ ; }, mesh = {Argentina ; Bacterial Proteins/genetics ; Bradyrhizobium/*isolation & purification/*metabolism ; Carbon-Carbon Lyases/genetics/*metabolism ; Nitrogen/metabolism ; Nitrogen Fixation/*physiology ; Plant Root Nodulation/*physiology ; Plant Roots/*microbiology ; Root Nodules, Plant/*metabolism ; Soybeans/*microbiology ; Symbiosis ; Transcription Factors/genetics ; }, abstract = {The purpose of this work was to study further two Bradyrhizobium japonicum strains with high nitrogen-fixing capacity that were identified within a collection of approximately 200 isolates from the soils of Argentina. Nodulation and nitrogen-fixing capacity and the level of expression of regulatory as well as structural genes of nitrogen fixation and the 1-aminocyclopropane-1-carboxylate (ACC) deaminase gene of the isolates were compared with that of E109-inoculated plants. Both isolates of B. japonicum, 163 and 366, were highly efficient to fix nitrogen compared to commercial strain E109. Isolate 366 developed a higher number and larger biomass of nodules and because of this fixed more nitrogen. Isolate 163 developed the same number and nodule biomass than E109. However, nodules developed by isolate 163 had red interiors for a longer period, had a higher leghemoglobin content, and presented high levels of expression of acdS gene, that codes for an ACC deaminase. In conclusion, naturalized rhizobia of the soils of Argentina hold a diverse population that might be the source of highly active nitrogen-fixing rhizobia, a process that appears to be based on different strategies.}, } @article {pmid29545511, year = {2018}, author = {Rosenberg, AB and Roco, CM and Muscat, RA and Kuchina, A and Sample, P and Yao, Z and Graybuck, LT and Peeler, DJ and Mukherjee, S and Chen, W and Pun, SH and Sellers, DL and Tasic, B and Seelig, G}, title = {Single-cell profiling of the developing mouse brain and spinal cord with split-pool barcoding.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {176-182}, doi = {10.1126/science.aam8999}, pmid = {29545511}, issn = {1095-9203}, support = {R01 CA207029/CA/NCI NIH HHS/United States ; R01 NS064404/NS/NINDS NIH HHS/United States ; R21 NS086500/NS/NINDS NIH HHS/United States ; TL1 TR002318/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Brain/*growth & development ; Cell Nucleus/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Developmental ; HEK293 Cells ; Humans ; Mice ; NIH 3T3 Cells ; Neurons/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis/*methods ; Spinal Cord/*growth & development ; *Transcriptome ; }, abstract = {To facilitate scalable profiling of single cells, we developed split-pool ligation-based transcriptome sequencing (SPLiT-seq), a single-cell RNA-seq (scRNA-seq) method that labels the cellular origin of RNA through combinatorial barcoding. SPLiT-seq is compatible with fixed cells or nuclei, allows efficient sample multiplexing, and requires no customized equipment. We used SPLiT-seq to analyze 156,049 single-nucleus transcriptomes from postnatal day 2 and 11 mouse brains and spinal cords. More than 100 cell types were identified, with gene expression patterns corresponding to cellular function, regional specificity, and stage of differentiation. Pseudotime analysis revealed transcriptional programs driving four developmental lineages, providing a snapshot of early postnatal development in the murine central nervous system. SPLiT-seq provides a path toward comprehensive single-cell transcriptomic analysis of other similarly complex multicellular systems.}, } @article {pmid29545510, year = {2018}, author = {Deino, AL and Behrensmeyer, AK and Brooks, AS and Yellen, JE and Sharp, WD and Potts, R}, title = {Chronology of the Acheulean to Middle Stone Age transition in eastern Africa.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {95-98}, doi = {10.1126/science.aao2216}, pmid = {29545510}, issn = {1095-9203}, mesh = {History, Ancient ; Human Activities/*history ; Humans ; Industrial Development/*history ; Kenya ; }, abstract = {The origin of the Middle Stone Age (MSA) marks the transition from a highly persistent mode of stone toolmaking, the Acheulean, to a period of increasing technological innovation and cultural indicators associated with the evolution of Homo sapiens We used argon-40/argon-39 and uranium-series dating to calibrate the chronology of Acheulean and early MSA artifact-rich sedimentary deposits in the Olorgesailie basin, southern Kenya rift. We determined the age of late Acheulean tool assemblages from 615,000 to 499,000 years ago, after which a large technological and faunal transition occurred, with a definitive MSA lacking Acheulean elements beginning most likely by ~320,000 years ago, but at least by 305,000 years ago. These results establish the oldest repository of MSA artifacts in eastern Africa.}, } @article {pmid29545509, year = {2018}, author = {Atabay, KD and LoCascio, SA and de Hoog, T and Reddien, PW}, title = {Self-organization and progenitor targeting generate stable patterns in planarian regeneration.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {404-409}, pmid = {29545509}, issn = {1095-9203}, support = {//Howard Hughes Medical Institute/United States ; R01 GM080639/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Movement ; Eye/*cytology/*transplantation ; Gene Expression Regulation, Developmental ; *Ocular Physiological Phenomena ; Ophthalmologic Surgical Procedures ; Planarians/cytology/*physiology ; Regeneration/genetics/*physiology ; Stem Cells/*physiology ; }, abstract = {During animal regeneration, cells must organize into discrete and functional systems. We show that self-organization, along with patterning cues, govern progenitor behavior in planarian regeneration. Surgical paradigms allowed the manipulation of planarian eye regeneration in predictable locations and numbers, generating alternative stable neuroanatomical states for wild-type animals with multiple functional ectopic eyes. We used animals with multiple ectopic eyes and eye transplantation to demonstrate that broad progenitor specification, combined with self-organization, allows anatomy maintenance during regeneration. We propose a model for regenerative progenitors involving (i) migratory targeting cues, (ii) self-organization into existing or regenerating eyes, and (iii) a broad zone, associated with coarse progenitor specification, in which eyes can be targeted by progenitors. These three properties help explain how tissues can be organized during regeneration.}, } @article {pmid29545508, year = {2018}, author = {Brooks, AS and Yellen, JE and Potts, R and Behrensmeyer, AK and Deino, AL and Leslie, DE and Ambrose, SH and Ferguson, JR and d'Errico, F and Zipkin, AM and Whittaker, S and Post, J and Veatch, EG and Foecke, K and Clark, JB}, title = {Long-distance stone transport and pigment use in the earliest Middle Stone Age.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {90-94}, doi = {10.1126/science.aao2646}, pmid = {29545508}, issn = {1095-9203}, mesh = {Adaptation, Psychological ; Coloring Agents/*history ; History, Ancient ; *Human Characteristics ; Humans ; Kenya ; Social Behavior/*history ; Socioeconomic Factors/*history ; }, abstract = {Previous research suggests that the complex symbolic, technological, and socioeconomic behaviors that typify Homo sapiens had roots in the middle Pleistocene <200,000 years ago, but data bearing on human behavioral origins are limited. We present a series of excavated Middle Stone Age sites from the Olorgesailie basin, southern Kenya, dating from ≥295,000 to ~320,000 years ago by argon-40/argon-39 and uranium-series methods. Hominins at these sites made prepared cores and points, exploited iron-rich rocks to obtain red pigment, and procured stone tool materials from ≥25- to 50-kilometer distances. Associated fauna suggests a broad resource strategy that included large and small prey. These practices imply notable changes in how individuals and groups related to the landscape and to one another and provide documentation relevant to human social and cognitive evolution.}, } @article {pmid29545507, year = {2018}, author = {van de Loosdrecht, M and Bouzouggar, A and Humphrey, L and Posth, C and Barton, N and Aximu-Petri, A and Nickel, B and Nagel, S and Talbi, EH and El Hajraoui, MA and Amzazi, S and Hublin, JJ and Pääbo, S and Schiffels, S and Meyer, M and Haak, W and Jeong, C and Krause, J}, title = {Pleistocene North African genomes link Near Eastern and sub-Saharan African human populations.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6388}, pages = {548-552}, doi = {10.1126/science.aar8380}, pmid = {29545507}, issn = {1095-9203}, mesh = {Africa South of the Sahara ; Africa, Northern ; African Continental Ancestry Group/*genetics ; Animals ; DNA, Ancient ; European Continental Ancestry Group ; *Evolution, Molecular ; Female ; Gene Flow ; *Genome, Human ; *Genome, Mitochondrial ; Genome-Wide Association Study ; Humans ; Mice ; Middle East ; Polymorphism, Single Nucleotide ; }, abstract = {North Africa is a key region for understanding human history, but the genetic history of its people is largely unknown. We present genomic data from seven 15,000-year-old modern humans, attributed to the Iberomaurusian culture, from Morocco. We find a genetic affinity with early Holocene Near Easterners, best represented by Levantine Natufians, suggesting a pre-agricultural connection between Africa and the Near East. We do not find evidence for gene flow from Paleolithic Europeans to Late Pleistocene North Africans. The Taforalt individuals derive one-third of their ancestry from sub-Saharan Africans, best approximated by a mixture of genetic components preserved in present-day West and East Africans. Thus, we provide direct evidence for genetic interactions between modern humans across Africa and Eurasia in the Pleistocene.}, } @article {pmid29545506, year = {2018}, author = {Potts, R and Behrensmeyer, AK and Faith, JT and Tryon, CA and Brooks, AS and Yellen, JE and Deino, AL and Kinyanjui, R and Clark, JB and Haradon, CM and Levin, NE and Meijer, HJM and Veatch, EG and Owen, RB and Renaut, RW}, title = {Environmental dynamics during the onset of the Middle Stone Age in eastern Africa.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {86-90}, doi = {10.1126/science.aao2200}, pmid = {29545506}, issn = {1095-9203}, mesh = {*Adaptation, Psychological ; Animals ; *Behavior ; *Biological Evolution ; History, Ancient ; Hominidae/*psychology ; *Human Characteristics ; Humans ; Kenya ; Lakes ; Paleontology ; }, abstract = {Development of the African Middle Stone Age (MSA) before 300,000 years ago raises the question of how environmental change influenced the evolution of behaviors characteristic of early Homo sapiens We used temporally well-constrained sedimentological and paleoenvironmental data to investigate environmental dynamics before and after the appearance of the early MSA in the Olorgesailie basin, Kenya. In contrast to the Acheulean archeological record in the same basin, MSA sites are associated with a markedly different faunal community, more pronounced erosion-deposition cycles, tectonic activity, and enhanced wet-dry variability. Aspects of Acheulean technology in this region imply that, as early as 615,000 years ago, greater stone material selectivity and wider resource procurement coincided with an increased pace of land-lake fluctuation, potentially anticipating the adaptability of MSA hominins.}, } @article {pmid29545273, year = {2018}, author = {Roach, JP and Pidde, A and Katz, E and Wu, J and Ognjanovski, N and Aton, SJ and Zochowski, MR}, title = {Resonance with subthreshold oscillatory drive organizes activity and optimizes learning in neural networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3017-E3025}, pmid = {29545273}, issn = {1091-6490}, support = {DP2 MH104119/MH/NIMH NIH HHS/United States ; R01 EB018297/EB/NIBIB NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; Animals ; Computer Simulation ; Ion Channels/physiology ; Learning/*physiology ; Mice ; *Models, Neurological ; Nerve Net/*physiology ; *Neural Networks (Computer) ; Neurons/*physiology ; Rhodopsin/*physiology ; }, abstract = {Network oscillations across and within brain areas are critical for learning and performance of memory tasks. While a large amount of work has focused on the generation of neural oscillations, their effect on neuronal populations' spiking activity and information encoding is less known. Here, we use computational modeling to demonstrate that a shift in resonance responses can interact with oscillating input to ensure that networks of neurons properly encode new information represented in external inputs to the weights of recurrent synaptic connections. Using a neuronal network model, we find that due to an input current-dependent shift in their resonance response, individual neurons in a network will arrange their phases of firing to represent varying strengths of their respective inputs. As networks encode information, neurons fire more synchronously, and this effect limits the extent to which further "learning" (in the form of changes in synaptic strength) can occur. We also demonstrate that sequential patterns of neuronal firing can be accurately stored in the network; these sequences are later reproduced without external input (in the context of subthreshold oscillations) in both the forward and reverse directions (as has been observed following learning in vivo). To test whether a similar mechanism could act in vivo, we show that periodic stimulation of hippocampal neurons coordinates network activity and functional connectivity in a frequency-dependent manner. We conclude that resonance with subthreshold oscillations provides a plausible network-level mechanism to accurately encode and retrieve information without overstrengthening connections between neurons.}, } @article {pmid29545272, year = {2018}, author = {Edington, SC and Gonzalez, A and Middendorf, TR and Halling, DB and Aldrich, RW and Baiz, CR}, title = {Coordination to lanthanide ions distorts binding site conformation in calmodulin.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3126-E3134}, pmid = {29545272}, issn = {1091-6490}, support = {R01 NS077821/NS/NINDS NIH HHS/United States ; }, mesh = {Binding Sites ; Calcium/chemistry/*metabolism ; Calmodulin/*chemistry/*metabolism ; Humans ; Lanthanoid Series Elements/chemistry/*metabolism ; Models, Molecular ; Protein Binding ; *Protein Conformation ; Protein Domains ; }, abstract = {The Ca2+-sensing protein calmodulin (CaM) is a popular model of biological ion binding since it is both experimentally tractable and essential to survival in all eukaryotic cells. CaM modulates hundreds of target proteins and is sensitive to complex patterns of Ca2+ exposure, indicating that it functions as a sophisticated dynamic transducer rather than a simple on/off switch. Many details of this transduction function are not well understood. Fourier transform infrared (FTIR) spectroscopy, ultrafast 2D infrared (2D IR) spectroscopy, and electronic structure calculations were used to probe interactions between bound metal ions (Ca2+ and several trivalent lanthanide ions) and the carboxylate groups in CaM's EF-hand ion-coordinating sites. Since Tb3+ is commonly used as a luminescent Ca2+ analog in studies of protein-ion binding, it is important to characterize distinctions between the coordination of Ca2+ and the lanthanides in CaM. Although functional assays indicate that Tb3+ fully activates many Ca2+-dependent proteins, our FTIR spectra indicate that Tb3+, La3+, and Lu3+ disrupt the bidentate coordination geometry characteristic of the CaM binding sites' strongly conserved position 12 glutamate residue. The 2D IR spectra indicate that, relative to the Ca2+-bound form, lanthanide-bound CaM exhibits greater conformational flexibility and larger structural fluctuations within its binding sites. Time-dependent 2D IR lineshapes indicate that binding sites in Ca2+-CaM occupy well-defined configurations, whereas binding sites in lanthanide-bound-CaM are more disordered. Overall, the results show that binding to lanthanide ions significantly alters the conformation and dynamics of CaM's binding sites.}, } @article {pmid29545110, year = {2018}, author = {Adamowicz, SJ and Marinone, MC and Menu-Marque, S and Martin, JW and Allen, DC and Pyle, MN and De Los Ríos, P and Sobel, CN and Ibañez, C and Pinto, J and Witt, JDS}, title = {The Hyalella (Crustacea: Amphipoda) species cloud of the ancient Lake Titicaca originated from multiple colonizations.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {232-242}, doi = {10.1016/j.ympev.2018.03.004}, pmid = {29545110}, issn = {1095-9513}, mesh = {Amphipoda/genetics/*physiology ; Animals ; Bayes Theorem ; Biodiversity ; Confidence Intervals ; Genetic Speciation ; Geography ; *Lakes ; Likelihood Functions ; Phylogeny ; Species Specificity ; Sympatry ; Time Factors ; }, abstract = {Ancient lakes are renowned for their exceptional diversity of endemic species. As model systems for the study of sympatric speciation, it is necessary to understand whether a given hypothesized species flock is of monophyletic or polyphyletic origin. Here, we present the first molecular characterization of the Hyalella (Crustacea: Amphipoda) species complex of Lake Titicaca, using COI and 28S DNA sequences, including samples from the connected Small and Large Lakes that comprise Lake Titicaca as well as from a broader survey of southern South American sites. At least five evolutionarily distant lineages are present within Lake Titicaca, which were estimated to have diverged from one another 12-20 MYA. These major lineages are dispersed throughout the broader South American Hyalella phylogeny, with each lineage representing at least one independent colonization of the lake. Moreover, complex genetic relationships are revealed between Lake Titicaca individuals and those from surrounding water bodies, which may be explained by repeated dispersal into and out of the lake, combined with parallel intralacustrine diversification within two separate clades. Although further work in deeper waters will be required to determine the number of species present and modes of diversification, our results strongly indicate that this amphipod species cloud is polyphyletic with a complex geographic history.}, } @article {pmid29545109, year = {2018}, author = {Lima, MGM and Silva-Júnior, JSE and Černý, D and Buckner, JC and Aleixo, A and Chang, J and Zheng, J and Alfaro, ME and Martins, A and Di Fiore, A and Boubli, JP and Lynch Alfaro, JW}, title = {A phylogenomic perspective on the robust capuchin monkey (Sapajus) radiation: First evidence for extensive population admixture across South America.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {137-150}, doi = {10.1016/j.ympev.2018.02.023}, pmid = {29545109}, issn = {1095-9513}, mesh = {Animals ; Calibration ; Cebinae ; Cebus/*classification/*genetics ; Ecosystem ; *Gene Pool ; Genetics, Population ; *Genomics ; Geography ; Likelihood Functions ; *Phylogeny ; Polymorphism, Single Nucleotide/genetics ; South America ; }, abstract = {Phylogenetic relationships amongst the robust capuchin monkeys (genus Sapajus) are poorly understood. Morphology-based taxonomies have recognized anywhere from one to twelve different species. The current IUCN (2017) classification lists eight robust capuchins: S. xanthosternos, S. nigritus, S. robustus, S. flavius, S. libidinosus, S. cay, S. apella and S. macrocephalus. Here, we assembled the first phylogenomic data set for Sapajus using ultra-conserved elements (UCEs) to reconstruct a capuchin phylogeny. All phylogenomic analyses strongly supported a deep divergence of Sapajus and Cebus clades within the capuchin monkeys, and provided support for Sapajus nigritus, S. robustus and S. xanthosternos as distinct species. However, the UCE phylogeny lumped the putative species S. cay, S. libidinosus, S. apella, S. macrocephalus, and S. flavius together as a single widespread lineage. A SNP phylogeny constructed from the UCE data was better resolved and recovered S. flavius and S. libidinosus as sister species; however, S. apella, S. macrocephalus, and S. cay individuals were recovered in two geographic clades, from northeastern and southwestern Amazon, rather than clustering by currently defined morphospecies. STRUCTURE analysis of population clustering revealed widespread admixture among Sapajus populations within the Amazon and even into the Cerrado and Atlantic Forest. Difficulty in assigning species by morphology may be a result of widespread population admixture facilitated through frequent movement across major rivers and even ecosystems by robust capuchin monkeys.}, } @article {pmid29544966, year = {2018}, author = {Koepfli, C and Yan, G}, title = {Plasmodium Gametocytes in Field Studies: Do We Measure Commitment to Transmission or Detectability?.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {378-387}, pmid = {29544966}, issn = {1471-5007}, support = {D43 TW001505/TW/FIC NIH HHS/United States ; R01 AI050243/AI/NIAID NIH HHS/United States ; U19 AI129326/AI/NIAID NIH HHS/United States ; }, mesh = {Environment ; Humans ; Malaria, Falciparum/epidemiology/*parasitology/transmission ; Parasitemia/*parasitology ; Plasmodium falciparum/cytology ; }, abstract = {The proportion of Plasmodium spp. infections carrying gametocytes, and gametocyte densities, are often reported as surrogate markers for transmission potential. It remains unclear whether parasites under natural conditions adjust commitment to transmission depending on external factors. Population-based surveys comprising mostly asymptomatic low-density infections are always impacted by the sensitivity of the assays used to diagnose infections and detect gametocytes. Asexual parasite density is an important predictor for the probability of detecting gametocytes, and in many cases it can explain patterns in gametocyte carriage without the need for an adjustment of the gametocyte conversion rate. When reporting gametocyte data, quantification of blood-stage parasitemia and its inclusion as a confounder in multivariable analyses is essential.}, } @article {pmid29544769, year = {2018}, author = {Assis-Ribas, T and Forni, MF and Winnischofer, SMB and Sogayar, MC and Trombetta-Lima, M}, title = {Extracellular matrix dynamics during mesenchymal stem cells differentiation.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {63-74}, doi = {10.1016/j.ydbio.2018.03.002}, pmid = {29544769}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation/*physiology ; Extracellular Matrix/*metabolism ; Humans ; Mesenchymal Stem Cells/*cytology/metabolism/physiology ; Signal Transduction/physiology ; }, abstract = {Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but is not restricted to: fat, bone and cartilage. Their potential importance for both cell therapy and maintenance of in vivo homeostasis is indisputable. Nonetheless, both their in vivo identity and use in cell therapy remain elusive. A drawback generated by this fact is that little is known about the MSC niche and how it impacts differentiation and homeostasis maintenance. Hence, the roles played by the extracellular matrix (ECM) and its main regulators namely: the Matrix Metalloproteinases (MMPs) and their counteracting inhibitors (TIMPs and RECK) upon stem cells differentiation are only now beginning to be unveiled. Here, we will focus on mesenchymal stem cells and review the main mechanisms involved in adipo, chondro and osteogenesis, discussing how the extracellular matrix can impact not only lineage commitment, but, also, their survival and potentiality. This review critically analyzes recent work in the field in an effort towards a better understanding of the roles of Matrix Metalloproteinases and their inhibitors in the above-cited events.}, } @article {pmid29544623, year = {2018}, author = {Paine, OCC and Koppa, A and Henry, AG and Leichliter, JN and Codron, D and Codron, J and Lambert, JE and Sponheimer, M}, title = {Grass leaves as potential hominin dietary resources.}, journal = {Journal of human evolution}, volume = {117}, number = {}, pages = {44-52}, doi = {10.1016/j.jhevol.2017.10.013}, pmid = {29544623}, issn = {1095-8606}, abstract = {Discussions about early hominin diets have generally excluded grass leaves as a staple food resource, despite their ubiquity in most early hominin habitats. In particular, stable carbon isotope studies have shown a prevalent C4 component in the diets of most taxa, and grass leaves are the single most abundant C4 resource in African savannas. Grass leaves are typically portrayed as having little nutritional value (e.g., low in protein and high in fiber) for hominins lacking specialized digestive systems. It has also been argued that they present mechanical challenges (i.e., high toughness) for hominins with bunodont dentition. Here, we compare the nutritional and mechanical properties of grass leaves with the plants growing alongside them in African savanna habitats. We also compare grass leaves to the leaves consumed by other hominoids and demonstrate that many, though by no means all, compare favorably with the nutritional and mechanical properties of known primate foods. Our data reveal that grass leaves exhibit tremendous variation and suggest that future reconstructions of hominin dietary ecology take a more nuanced approach when considering grass leaves as a potential hominin dietary resource.}, } @article {pmid29544622, year = {2018}, author = {Best, A and Kamilar, JM}, title = {The evolution of eccrine sweat glands in human and nonhuman primates.}, journal = {Journal of human evolution}, volume = {117}, number = {}, pages = {33-43}, doi = {10.1016/j.jhevol.2017.12.003}, pmid = {29544622}, issn = {1095-8606}, abstract = {Sweating is an unusual thermoregulatory strategy for most mammals, yet is critical for humans. This trait is commonly hypothesized to result from human ancestors moving from a forest to a warmer and drier open environment. As soft tissue traits do not typically fossilize, this idea has been difficult to test. Therefore, we used a comparative approach to examine 15 eccrine gland traits from 35 primate species. For each trait we measured phylogenetic signal, tested three evolutionary models to explain trait variation, and used phylogenetic models to examine how traits varied in response to climate variables. Phylogenetic signal in traits varied substantially, with the two traits exhibiting the highest values being gland distribution on the body and percent eccrine vs. apocrine glands on the body. Variation in most traits was best explained by an Ornstein-Uhlenbeck model suggesting the importance of natural selection. Two traits were strongly predicted by climate. First, species with high eccrine gland glycogen content were associated with habitats exhibiting warm temperatures and low rainfall. Second, species with increased capillarization were associated with high temperature. Glycogen is a primary energy substrate powering sweat production and sodium reabsorption in the eccrine gland, and increased capillarization permits greater oxygen, glucose and electrolyte delivery. Thus, our results are evidence of natural selection for increased sweating capacity in primate species with body surface eccrine glands living in hot and dry climates. We suggest that selection for increased glycogen content and capillarization may have been part of initial increases in hominin thermoregulatory sweating capacity.}, } @article {pmid29544621, year = {2018}, author = {Gómez-Olivencia, A and Quam, R and Sala, N and Bardey, M and Ohman, JC and Balzeau, A}, title = {La Ferrassie 1: New perspectives on a "classic" Neandertal.}, journal = {Journal of human evolution}, volume = {117}, number = {}, pages = {13-32}, doi = {10.1016/j.jhevol.2017.12.004}, pmid = {29544621}, issn = {1095-8606}, abstract = {The La Ferrassie 1 (LF1) skeleton, discovered over a century ago, is one of the most important Neandertal individuals both for its completeness and due to the role it has played historically in the interpretation of Neandertal anatomy and lifeways. Here we present new skeletal remains from this individual, which include a complete right middle ear ossicular chain (malleus, incus, and stapes), three vertebral fragments, and two costal remains. Additionally, the study of the skeleton has allowed us to identify new pathological lesions, including a congenital variant in the atlas, a greenstick fracture of the left clavicle, and a lesion in a mid-thoracic rib of unknown etiology. In addition, we have quantified the amount of vertebral pathology, which is greater than previously appreciated. We have complemented the paleopathological analysis with a taphonomic analysis to identify any potential perimortem fractures. The taphonomic analysis indicates that no surface alteration is present in the LF1 skeleton and that the breakage pattern is that of bone that has lost collagen, which would be consistent with the intentional burial of this individual proposed by previous researchers. In this study, we used CT and microCT scans in order to discover new skeletal elements to better characterize the pathological lesions and to quantify the fracture orientation of those bones in which the current plaster reconstruction did not allow its direct visualization, which underlines the broad potential of imaging technologies in paleoanthropological research. A century after its discovery, LF1 is still providing new insights into Neandertal anatomy and behavior.}, } @article {pmid29544620, year = {2018}, author = {Rodríguez, L and Carretero, JM and García-González, R and Arsuaga, JL}, title = {Cross-sectional properties of the lower limb long bones in the Middle Pleistocene Sima de los Huesos sample (Sierra de Atapuerca, Spain).}, journal = {Journal of human evolution}, volume = {117}, number = {}, pages = {1-12}, doi = {10.1016/j.jhevol.2017.11.007}, pmid = {29544620}, issn = {1095-8606}, abstract = {The recovery to date of three complete and five partial femora, seven complete tibiae, and four complete fibulae from the Atapuerca Sima de los Huesos site provides an opportunity to analyze the biomechanical cross-sectional properties in this Middle Pleistocene population and to compare them with those of other fossil hominins and recent modern humans. We have performed direct comparisons of the cross-sectional geometric parameters and reduced major axis (RMA) regression lines among different samples. We have determined that Atapuerca Sima de los Huesos (SH) fossils have significantly thicker cortices than those of recent modern humans for the three leg bones at all diaphyseal levels, except that of the femur at 35% of biomechanical length. The SH bones are similar to those of Neandertals and Middle Pleistocene humans and different from Homo sapiens in their diaphyseal cross-sectional shape and strength parameters. When standardized by estimated body size, both the SH and Neandertal leg bones have in general greater strength than those of H. sapiens from the early modern (EMH), Upper Paleolithic (UP), and recent populations (RH). The Sima de los Huesos human leg bones have, in general terms, an ancestral pattern similar to that of Pleistocene humans and differing from H. sapiens.}, } @article {pmid29544540, year = {2018}, author = {Joyce, B and Lee, D and Rubio, A and Ogurtsov, A and Alves, G and Yu, YK}, title = {A graphical user interface for RAId, a knowledge integrated proteomics analysis suite with accurate statistics.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {182}, pmid = {29544540}, issn = {1756-0500}, support = {Intramural Research Program//U.S. National Library of Medicine/ ; }, mesh = {Computational Biology/*methods ; Databases, Protein ; Humans ; Internet ; Proteome/*analysis ; Proteomics/*methods ; *Software ; Tandem Mass Spectrometry/methods ; *User-Computer Interface ; }, abstract = {OBJECTIVE: RAId is a software package that has been actively developed for the past 10 years for computationally and visually analyzing MS/MS data. Founded on rigorous statistical methods, RAId's core program computes accurate E-values for peptides and proteins identified during database searches. Making this robust tool readily accessible for the proteomics community by developing a graphical user interface (GUI) is our main goal here.

RESULTS: We have constructed a graphical user interface to facilitate the use of RAId on users' local machines. Written in Java, RAId_GUI not only makes easy executions of RAId but also provides tools for data/spectra visualization, MS-product analysis, molecular isotopic distribution analysis, and graphing the retrieval versus the proportion of false discoveries. The results viewer displays and allows the users to download the analyses results. Both the knowledge-integrated organismal databases and the code package (containing source code, the graphical user interface, and a user manual) are available for download at https://www.ncbi.nlm.nih.gov/CBBresearch/Yu/downloads/raid.html .}, } @article {pmid29544538, year = {2018}, author = {Noury, AE and Azmy, O and Alsharnoubi, J and Salama, S and Okasha, A and Gouda, W}, title = {Variants of CDKAL1 rs7754840 (G/C) and CDKN2A/2B rs10811661 (C/T) with gestational diabetes: insignificant association.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {181}, pmid = {29544538}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Alleles ; Cyclin-Dependent Kinase Inhibitor p15/*genetics ; Cyclin-Dependent Kinase Inhibitor p18/*genetics ; Diabetes Mellitus, Type 2/genetics ; Diabetes, Gestational/*genetics ; Female ; Gene Frequency ; Genetic Predisposition to Disease/*genetics ; Genotype ; Humans ; Logistic Models ; Middle Aged ; *Polymorphism, Single Nucleotide ; Pregnancy ; Young Adult ; tRNA Methyltransferases/*genetics ; }, abstract = {OBJECTIVES: Pathophysiological similarity exists between gestational diabetes mellitus (GDM) and type 2 diabetes mellitus with common genetic origin. Genetic liability for GDM in our population is still not researched. The goal was to reveal the genotypic and allele frequency differences of 2 single nucleotide polymorphisms (SNPs) namely, CDKAL1 (rs7754840) and CDKN2A/2B (rs10811661) between GDM pregnancies and normal pregnancies. We assessed them by real time polymerase chain reaction using Taqman® allelic discrimination assays. We included 47 GDM pregnant subjects and 51 normal glucose tolerance (NGT) pregnant women as controls.

RESULTS: The genotype frequencies in the GDM group and the NGT group of rs7754840-GG/GC/CC were 6.4/15.7% (3/8), 55.3/45.1% (26/23) and 38.3/39.2% (18/20) respectively. Also, those of rs10811661-CC/CT/TT were 74.5/14.9/4.3% (38/7/2) and 80.9/19.6/5.9% (38/10/3) respectively. The allele frequencies in the GDM group and the NGT group of C/G and T/C were 66/34% (62/32), 61.8/38.2% (63/39) and 11.7/88.3% (11/83), 15.7/84.3% (16/86) respectively. There were no statistical differences between the two groups in allele frequencies and genotype frequencies (all P > 0.05). Non-significant association was seen in the two SNPs of CDKAL1 and CDKN2A/B genes with GDM. Further studies are essential to validate data.}, } @article {pmid29544531, year = {2018}, author = {Afaneh, A and Ford, J and Gharzeddine, J and Mazar, A and Hayward, RD and Buck, J}, title = {Head injury on Warfarin: likelihood of delayed intracranial bleeding in patients with negative initial head CT.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {183}, pmid = {29544531}, issn = {1756-0500}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anticoagulants/therapeutic use ; Female ; Head Injuries, Closed/complications/*diagnostic imaging/*drug therapy ; Humans ; International Normalized Ratio ; Intracranial Hemorrhages/etiology/*prevention & control ; Male ; Middle Aged ; Retrospective Studies ; Time Factors ; Tomography, X-Ray Computed/*methods ; Warfarin/*therapeutic use ; Young Adult ; }, abstract = {OBJECTIVE: To determine the likelihood that head injured patients on Warfarin with a negative initial head CT will have a positive repeat head CT. A retrospective chart review of our institution's trauma registry was performed for all patients admitted for blunt head trauma and on Warfarin anti-coagulation from January 2009 to April 2014. Inclusion criteria included patients over 18 years of age with initial GCS ≥ 13, INR greater than 1.5 and negative initial head CT. Initial CT findings, repeat CT findings and INR were recorded. Interventions performed on patients with a delayed bleed were also investigated.

RESULTS: 394 patients met the study inclusion criteria. 121 (31%) of these patients did not receive a second CT while 273 patients (69%) underwent a second CT. The mean INR was 2.74. Six patients developed a delayed bleed, of which two were clinically significant. No patients had any neurosurgical intervention. Our results demonstrate a low rate of delayed bleeding. The utility of repeat head CT in the neurologically stable patient is thus questioned. Patients who have an abnormal baseline neurological status and those with INR >3 may represent a subgroup of patients in whom repeat head CT should be performed.}, } @article {pmid29544468, year = {2018}, author = {Maurer, JM and Sagerström, CG}, title = {A parental requirement for dual-specificity phosphatase 6 in zebrafish.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {6}, pmid = {29544468}, issn = {1471-213X}, support = {R01 NS038183/NS/NINDS NIH HHS/United States ; R56 NS038183/NS/NINDS NIH HHS/United States ; NS038183//Foundation for the National Institutes of Health/International ; }, abstract = {BACKGROUND: Signaling cascades, such as the extracellular signal-regulated kinase (ERK) pathway, play vital roles in early vertebrate development. Signals through these pathways are initiated by a growth factor or hormone, are transduced through a kinase cascade, and result in the expression of specific downstream genes that promote cellular proliferation, growth, or differentiation. Tight regulation of these signals is provided by positive or negative modulators at varying levels in the pathway, and is required for proper development and function. Two members of the dual-specificity phosphatase (Dusp) family, dusp6 and dusp2, are believed to be negative regulators of the ERK pathway and are expressed in both embryonic and adult zebrafish, but their specific roles in embryogenesis remain to be fully understood.

RESULTS: Using CRISPR/Cas9 genome editing technology, we generated zebrafish lines harboring germ line deletions in dusp6 and dusp2. We do not detect any overt defects in dusp2 mutants, but we find that approximately 50% of offspring from homozygous dusp6 mutants do not proceed through embryonic development. These embryos are fertilized, but are unable to proceed past the first zygotic mitosis and stall at the 1-cell stage for several hours before dying by 10 h post fertilization. We demonstrate that dusp6 is expressed in gonads of both male and female zebrafish, suggesting that loss of dusp6 causes defects in germ cell production. Notably, the 50% of homozygous dusp6 mutants that complete the first cell division appear to progress through embryogenesis normally and give rise to fertile adults.

CONCLUSIONS: The fact that offspring of homozygous dusp6 mutants stall prior to activation of the zygotic genome, suggests that loss of dusp6 affects gametogenesis and/or parentally-directed early development. Further, since only approximately 50% of homozygous dusp6 mutants are affected, we postulate that ERK signaling is tightly regulated and that dusp6 is required to keep ERK signaling within a range that is permissive for proper embryogenesis. Lastly, since dusp6 is expressed throughout zebrafish embryogenesis, but dusp6 mutants do not exhibit defects after the first cell division, it is possible that other regulators of the ERK pathway compensate for loss of dusp6 at later stages.}, } @article {pmid29544443, year = {2018}, author = {Mißbach, S and Aleksic, D and Blaschke, L and Hassemer, T and Lee, KJ and Mansfeld, M and Hänske, J and Handler, J and Kammerer, R}, title = {Alternative splicing after gene duplication drives CEACAM1-paralog diversification in the horse.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {32}, pmid = {29544443}, issn = {1471-2148}, support = {(KF2875802UL2)//Bundesministerium für Wirtschaft und Technologie/International ; (Contract no. 81170269; Project No. 13.1432.7---001.00)//Gesellschaft für internationale Zusammenarbeit/International ; HE 6249/4-1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Alternative Splicing/*genetics ; Amino Acid Motifs ; Amino Acid Sequence ; Animals ; Antigens, CD/chemistry/*genetics ; Base Sequence ; Cell Adhesion Molecules/chemistry/*genetics ; Codon/genetics ; Exons/genetics ; *Gene Duplication ; *Genetic Variation ; Horses/*genetics ; Humans ; Leukocytes, Mononuclear/metabolism ; Protein Domains ; Protein Isoforms/genetics ; RNA, Messenger/genetics/metabolism ; Rabbits ; *Sequence Homology, Nucleic Acid ; }, abstract = {BACKGROUND: The CEA gene family is one of the most rapidly evolving gene families in the human genome. The founder gene of the family is thought to be an ancestor of the inhibitory immune checkpoint molecule CEACAM1. Comprehensive analyses of mammalian genomes showed that the CEA gene family is subject to tremendous gene family expansion and contraction events in different mammalian species. While in some species (e.g. rabbits) less than three CEACAM1 related genes exist, were in others (certain microbat species) up to 100 CEACAM1 paralogs identified. We have recently reported that the horse has also an extended CEA gene family. Since mechanisms of gene family expansion and diversification are not well understood we aimed to analyze the equine CEA gene family in detail.

RESULTS: We found that the equine CEA gene family contains 17 functional CEACAM1-related genes. Nine of them were secreted molecules and eight CEACAMs contain transmembrane and cytoplasmic domain exons, the latter being in the focus of the present report. Only one (CEACAM41) gene has exons coding for activating signaling motifs all other CEACAM1 paralogs contain cytoplasmic exons similar to that of the inhibitory receptor CEACAM1. However, cloning of cDNAs showed that only one CEACAM1 paralog contain functional immunoreceptor tyrosine-based inhibitory motifs in its cytoplasmic tail. Three receptors have acquired a stop codon in the transmembrane domain and two have lost their inhibitory motifs due to alternative splicing events. In addition, alternative splicing eliminated the transmembrane exon sequence of the putative activating receptor, rendering it to a secreted molecule. Transfection of eukaryotic cells with FLAG-tagged alternatively spliced CEACAMs indicates that they can be expressed in vivo. Thus detection of CEACAM41 mRNA in activated PBMC suggests that CEACAM41 is secreted by lymphoid cells upon activation.

CONCLUSIONS: The results of our study demonstrate that alternative splicing after gene duplication is a potent mechanism to accelerate functional diversification of the equine CEA gene family members. This potent mechanism has created novel CEACAM receptors with unique signaling capacities and secreted CEACAMs which potentially enables equine lymphoid cells to control distantly located immune cells.}, } @article {pmid29544440, year = {2018}, author = {Perrin, J and Bary, A and Vernay, A and Cosson, P}, title = {Role of the HIV-1 envelope transmembrane domain in intracellular sorting.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {3}, pmid = {29544440}, issn = {1471-2121}, support = {31003A-172951//Swiss National Science Foundation/Switzerland ; }, mesh = {Amino Acid Sequence ; Amino Acids/metabolism ; Cell Membrane ; Endoplasmic Reticulum/metabolism ; HIV-1/*metabolism ; HeLa Cells ; Humans ; Intracellular Space/*metabolism ; Lentivirus/metabolism ; Protein Domains ; Protein Transport ; Structure-Activity Relationship ; env Gene Products, Human Immunodeficiency Virus/*chemistry/*metabolism ; }, abstract = {BACKGROUND: The envelope protein of lentiviruses are type I transmembrane proteins, and their transmembrane domain contains conserved potentially charged residues. This highly unusual feature would be expected to cause endoplasmic reticulum (ER) localization. The aim of this study was to determine by which means the HIV-1 Env protein is transported to the cell surface although its transmembrane domain contains a conserved arginine residue.

RESULTS: We expressed various chimeric proteins and analyzed the influence of their transmembrane domain on their intracellular localization. The transmembrane domain of the HIV-1 Env protein does not cause ER retention. This is not due to the presence of conserved glycine residues, or to the position of the arginine residue, but to the length of the transmembrane domain. A shortened version of the Env transmembrane domain causes arginine-dependent ER targeting. Remarkably, the transmembrane domain of the HIV-1 Env protein, although it does not confer ER retention, interacts efficiently with negatively charged residues in the membrane.

CONCLUSION: These results suggest that the intrinsic properties of the HIV-1 Env transmembrane domain allow the protein to escape ER-retention mechanisms, while maintaining its ability to interact with cellular proteins and to influence cellular physiology.}, } @article {pmid29544125, year = {2018}, author = {Avalos, M and van Wezel, GP and Raaijmakers, JM and Garbeva, P}, title = {Healthy scents: microbial volatiles as new frontier in antibiotic research?.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {84-91}, doi = {10.1016/j.mib.2018.02.011}, pmid = {29544125}, issn = {1879-0364}, abstract = {Microorganisms represent a large and still resourceful pool for the discovery of novel compounds to combat antibiotic resistance in human and animal pathogens. The ability of microorganisms to produce structurally diverse volatile compounds has been known for decades, yet their biological functions and antimicrobial activities have only recently attracted attention. Various studies revealed that microbial volatiles can act as infochemicals in long-distance cross-kingdom communication as well as antimicrobials in competition and predation. Here, we review recent insights into the natural functions and modes of action of microbial volatiles and discuss their potential as a new class of antimicrobials and modulators of antibiotic resistance.}, } @article {pmid29544124, year = {2018}, author = {Basan, M}, title = {Resource allocation and metabolism: the search for governing principles.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {77-83}, doi = {10.1016/j.mib.2018.02.008}, pmid = {29544124}, issn = {1879-0364}, abstract = {Elucidating strategies of resource allocation and metabolism is crucial for a better understanding of microbial phenotypes. In particular, uncovering the governing principles underlying these processes would be a crucial step for achieving a central aim of systems microbiology, which is to quantitatively predict phenotypes of microbial cells or entire populations in diverse conditions. Here, some of the key concepts for understanding cellular resource allocation and metabolism that have been suggested over the past years are reviewed. In particular, recent experimental studies that have shown how phenotypic patterns from orthogonal genetic and environmental perturbations can help to differentiate between competing hypotheses and their respective predictions are discussed. Phenomenological models have proven to be a valuable addition to genome-scale models, capable of making quantitative predictions with only few parameters and having aided the identification of molecular mechanisms.}, } @article {pmid29543391, year = {2018}, author = {Talbot, B and Vonhof, MJ and Broders, HG and Fenton, B and Keyghobadi, N}, title = {Host association influences variation at salivary protein genes in the bat ectoparasite Cimex adjunctus.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {753-763}, doi = {10.1111/jeb.13265}, pmid = {29543391}, issn = {1420-9101}, abstract = {Parasite-host relationships create strong selection pressures that can lead to adaptation and increasing specialization of parasites to their hosts. Even in relatively loose host-parasite relationships, such as between generalist ectoparasites and their hosts, we may observe some degree of specialization of parasite populations to one of the multiple potential hosts. Salivary proteins are used by blood-feeding ectoparasites to prevent hemostasis in the host and maximize energy intake. We investigated the influence of association with specific host species on allele frequencies of salivary protein genes in Cimex adjunctus, a generalist blood-feeding ectoparasite of bats in North America. We analysed two salivary protein genes: an apyrase, which hydrolyses ATP at the feeding site and thus inhibits platelet aggregation, and a nitrophorin, which brings nitrous oxide to the feeding site, inhibiting platelet aggregation and vasoconstriction. We observed more variation at both salivary protein genes among parasite populations associated with different host species than among populations from different spatial locations associated with the same host species. The variation in salivary protein genes among populations on different host species was also greater than expected under a neutral scenario of genetic drift and gene flow. Finally, host species was an important predictor of allelic divergence in genotypes of individual C. adjunctus at both salivary protein genes. Our results suggest differing selection pressures on these two salivary protein genes in C. adjunctus depending on the host species.}, } @article {pmid29543151, year = {2018}, author = {Gcebe, N and Rutten, VPMG and van Pittius, NG and Naicker, B and Michel, AL}, title = {Mycobacterium komaniense sp. nov., a rapidly growing non-tuberculous Mycobacterium species detected in South Africa.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1526-1532}, doi = {10.1099/ijsem.0.002707}, pmid = {29543151}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Cattle/*microbiology ; DNA, Bacterial/genetics ; Genes, Bacterial ; Nontuberculous Mycobacteria/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; South Africa ; }, abstract = {Some species of non-tuberculous mycobacteria (NTM) have been reported to be opportunistic pathogens of animals and humans. Recently there has been an upsurge in the number of cases of NTM infections, such that some NTM species are now recognized as pathogens of humans and animals. From a veterinary point of view, the major significance of NTM is the cross-reactive immune response they elicit against Mycobacterium bovis antigens, leading to misdiagnosis of bovine tuberculosis. Four NTM isolates were detected from a bovine nasal swab, soil and water, during an NTM survey in South Africa. These were all found using 16S rRNA gene sequence analysis to be closely related to Mycobacterium moriokaense. The isolates were further characterised by sequence analysis of the partial fragments of hsp65, rpoB and sodA. The genome of the type strain was also elucidated. Gene (16S rRNA, hsp65, rpoB and sodA) and protein sequence data analysis of 6 kDa early secretory antigenic target (ESAT 6) and 10 kDa culture filtrate protein (CFP-10) revealed that these isolates belong to a unique Mycobacterium species. Differences in phenotypic and biochemical traits between the isolates and closely related species further supported that these isolates belong to novel Mycobacterium species. We proposed the name Mycobacterium komaniense sp. nov. for this new species. The type strain is GPK 1020T (=CIP 110823T=ATCC BAA-2758).}, } @article {pmid29543150, year = {2018}, author = {Chiba, M and Itabashi, T and Hirai, K and Sakamoto, M and Ohkuma, M and Ishige, T and Kawasaki, S}, title = {Lactobacillus metriopterae sp. nov., a novel lactic acid bacterium isolated from the gut of grasshopper Metrioptera engelhardti.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1484-1489}, doi = {10.1099/ijsem.0.002694}, pmid = {29543150}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Genes, Bacterial ; Grasshoppers/*microbiology ; Japan ; Lactobacillus/*classification/genetics/isolation & purification ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A strain (Hime 5-1T) of lactic acid bacterium was isolated from the gut of the grasshopper Metrioptera engelhardti from a mountainous area of Nagano Prefecture, Japan. Strain Hime 5-1T had a low 16S rRNA gene sequence similarity to known lactic acid bacteria, with the closest recognized relatives being Lactobacillus tucceti (96.7 %), Lactobacillus furfuricola (96.5 %), Lactobacillus versmoldensis (96.3 %) and Lactobacillus nodensis (96.1 %). Comparative analyses of the rpoA and pheS gene sequences indicated that Hime 5-1T is not closely related to other Lactobacillus species. Strain Hime 5-1T is a Gram-stain-positive, catalase-negative and homofermentative bacterium with yellowish colonies, which contrasts with the whitish colonies of its closest recognized relatives. Based on phenotypic and genotypic properties, we conclude that the isolated bacterium represents a novel species of the genus Lactobacillus, for which the name Lactobacillus metriopterae sp. nov. is proposed. The type strain is Hime 5-1T (=JCM 31635T=DSM 103730T). 16S rRNA gene based high-throughput sequencing revealed that L. metriopterae is the dominant microbiota in the gut of Metrioptera engelhardti.}, } @article {pmid29543147, year = {2018}, author = {Rachniyom, H and Matsumoto, A and Inahashi, Y and Take, A and Takahashi, Y and Thamchaipenet, A}, title = {Actinomadura barringtoniae sp. nov., an endophytic actinomycete isolated from the roots of Barringtonia acutangula (L.) Gaertn.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1584-1590}, doi = {10.1099/ijsem.0.002714}, pmid = {29543147}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Barringtonia/*microbiology ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Endophytes/classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Muramic Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/chemistry ; }, abstract = {A novel actinomycete strain, designated GKU 128T, isolated from the roots of an Indian oak tree [Barringtonia acutangula (L.) Gaertn.] at Khao Khitchakut district, Chantaburi province, Thailand, was characterized by using a polyphasic approach. The strain formed a branched substrate and aerial mycelia which differentiated into straight to flexuous chains of smooth-ornamented spores. Analysis of the cell wall revealed the presence of meso-diaminopimelic acid and N-acetylmuramic acid in the peptidoglycan. The whole-cell sugars were glucose, madurose, mannose, rhamnose and ribose. Mycolic acids were absent. The major phospholipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositolmannoside. The predominant menaquinones were MK-9(H6), MK-9(H8), MK-9(H0) and MK-9(H4). The major fatty acids were C16 : 0, C18 : 1ω9c and 10-methyl C18 : 0 (tuberculostearic acid). The genomic DNA G+C content was 70.5 mol%. Based on 16S rRNA gene sequence analysis, strain GKU 128T was closely related to the type strains of Actinomadura nitritigenes NBRC 15918T (99.2 % sequence similarity) and Actinomadura fibrosa JCM 9371T (98.7 %). The levels of DNA-DNA relatedness between strain GKU 128T and the closely related type species were less than 19 %. On the basis of phenotypic and genotypic characteristics, strain GKU 128T could be distinguished from its closely related type strains and represents a novel species of the genus Actinomadura, for which the name Actinomadura barringtoniae sp. nov. (=TBRC 7225T=NBRC 113074T) is proposed.}, } @article {pmid29542724, year = {2018}, author = {Tollefson, J}, title = {MIT launches multimillion-dollar collaboration to develop fusion energy.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {294-295}, doi = {10.1038/d41586-018-02966-3}, pmid = {29542724}, issn = {1476-4687}, } @article {pmid29542722, year = {2018}, author = {Seele, P and Helbing, D}, title = {Boost sustainability through social justice in China's Belt and Road Initiative.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {311}, doi = {10.1038/d41586-018-03051-5}, pmid = {29542722}, issn = {1476-4687}, mesh = {China ; *Social Justice ; }, } @article {pmid29542721, year = {2018}, author = {Schiermeier, Q}, title = {Russian science chases escape from mediocrity.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {297-298}, doi = {10.1038/d41586-018-02872-8}, pmid = {29542721}, issn = {1476-4687}, mesh = {Federal Government ; Research Support as Topic/economics/legislation & jurisprudence ; Russia ; Science/economics/legislation & jurisprudence/*standards/*trends ; USSR ; }, } @article {pmid29542719, year = {2018}, author = {Maxmen, A}, title = {AI researchers embrace Bitcoin technology to share medical data.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {293-294}, doi = {10.1038/d41586-018-02641-7}, pmid = {29542719}, issn = {1476-4687}, mesh = {*Models, Economic ; Research Personnel ; *Technology ; }, } @article {pmid29542718, year = {2018}, author = {McDannell, KT}, title = {Make supplementary reference lists visible for citation metrics.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {311}, doi = {10.1038/d41586-018-02965-4}, pmid = {29542718}, issn = {1476-4687}, mesh = {*Bibliometrics ; *Journal Impact Factor ; }, } @article {pmid29542717, year = {2018}, author = {}, title = {AI diagnostics need attention.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {285}, doi = {10.1038/d41586-018-03067-x}, pmid = {29542717}, issn = {1476-4687}, mesh = {*Artificial Intelligence ; *Diagnosis ; }, } @article {pmid29542716, year = {2018}, author = {Fruchart, M and Vitelli, V}, title = {Waves cornered.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {318-319}, doi = {10.1038/d41586-018-02868-4}, pmid = {29542716}, issn = {1476-4687}, } @article {pmid29542715, year = {2018}, author = {Saunders, R}, title = {Chronic fatigue syndrome therapies grounded in science hold promise.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {311}, doi = {10.1038/d41586-018-03055-1}, pmid = {29542715}, issn = {1476-4687}, mesh = {*Fatigue ; *Fatigue Syndrome, Chronic ; Humans ; }, } @article {pmid29542714, year = {2018}, author = {Paterlini, M}, title = {Laboratory balancing act.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {405}, doi = {10.1038/d41586-018-03072-0}, pmid = {29542714}, issn = {1476-4687}, } @article {pmid29542713, year = {2018}, author = {Irifune, T and Ohuchi, T}, title = {Oxidation softens mantle rocks.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {314-315}, doi = {10.1038/d41586-018-02828-y}, pmid = {29542713}, issn = {1476-4687}, } @article {pmid29542711, year = {2018}, author = {Casadevall, A}, title = {Melanin triggers antifungal defences.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {319-320}, doi = {10.1038/d41586-018-02370-x}, pmid = {29542711}, issn = {1476-4687}, mesh = {*Antifungal Agents ; Drug Resistance, Fungal/drug effects ; *Melanins ; }, } @article {pmid29542710, year = {2018}, author = {Angelo, C}, title = {Police probe of Brazilian marijuana researcher sparks protests.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {296}, doi = {10.1038/d41586-018-02842-0}, pmid = {29542710}, issn = {1476-4687}, mesh = {Alcoholism/drug therapy ; Animals ; Biomedical Research/*legislation & jurisprudence ; Brazil ; Cannabidiol/therapeutic use ; *Cannabis ; Dronabinol ; Epilepsy/drug therapy ; Freedom ; Humans ; Medical Marijuana ; *Police ; Psychopharmacology ; Research Personnel/*legislation & jurisprudence ; }, } @article {pmid29542709, year = {2018}, author = {Schiermeier, Q}, title = {Data management made simple.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {403-405}, doi = {10.1038/d41586-018-03071-1}, pmid = {29542709}, issn = {1476-4687}, mesh = {Confidentiality ; Copyright ; Financing, Organized/organization & administration ; Information Management/*education/*methods ; *Information Storage and Retrieval ; *Open Access Publishing ; *Research Design ; *Research Personnel/education/standards ; Research Report/*standards ; Research Support as Topic ; }, } @article {pmid29542707, year = {2018}, author = {Dolgin, E}, title = {What lava lamps and vinaigrette can teach us about cell biology.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {300-302}, doi = {10.1038/d41586-018-03070-2}, pmid = {29542707}, issn = {1476-4687}, mesh = {Alzheimer Disease/metabolism/pathology ; Amyotrophic Lateral Sclerosis/metabolism/pathology ; Animals ; Caenorhabditis elegans/chemistry/cytology ; Cell Biology ; Cells/*chemistry ; Humans ; Hydrogen-Ion Concentration ; *Models, Chemical ; Oils/chemistry ; RNA/chemistry ; tau Proteins/chemistry ; }, } @article {pmid29542706, year = {2018}, author = {Moore, JC and Gladstone, R and Zwinger, T and Wolovick, M}, title = {Geoengineer polar glaciers to slow sea-level rise.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {303-305}, doi = {10.1038/d41586-018-03036-4}, pmid = {29542706}, issn = {1476-4687}, mesh = {Antarctic Regions ; Ecosystem ; Feasibility Studies ; *Freezing/adverse effects ; Global Warming/economics/*statistics & numerical data ; Gravitation ; Greenland ; Hydrology/economics/*methods/trends ; Ice Cover/*chemistry ; Seawater/*analysis/*chemistry ; Temperature ; *Water Movements ; }, } @article {pmid29542704, year = {2018}, author = {Russell, J}, title = {Ocean sensors can track progress on climate goals.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {287}, doi = {10.1038/d41586-018-03068-w}, pmid = {29542704}, issn = {1476-4687}, mesh = {Carbon Dioxide/*analysis ; Environmental Policy/economics/*legislation & jurisprudence ; Global Warming/economics/legislation & jurisprudence/*prevention & control ; *Goals ; Greenhouse Effect/economics/legislation & jurisprudence/prevention & control ; International Cooperation/*legislation & jurisprudence ; *Oceans and Seas ; Seawater/*chemistry ; Uncertainty ; }, } @article {pmid29542703, year = {2018}, author = {Bandopadhayay, P and Meyerson, M}, title = {Landscapes of childhood tumours.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {316-317}, doi = {10.1038/d41586-018-01648-4}, pmid = {29542703}, issn = {1476-4687}, mesh = {Humans ; *Neoplasms ; }, } @article {pmid29542702, year = {2018}, author = {Altmann, D}, title = {Don't let peer review panels for grant awards turn into a wolf pack.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {311}, doi = {10.1038/d41586-018-03060-4}, pmid = {29542702}, issn = {1476-4687}, mesh = {Financing, Organized ; *Peer Review ; *Research Support as Topic ; }, } @article {pmid29542700, year = {2018}, author = {Hansson, N and Halling, T and Fangerau, H}, title = {Nobel nomination letters point to a winning formula.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {311}, doi = {10.1038/d41586-018-03057-z}, pmid = {29542700}, issn = {1476-4687}, mesh = {*Nobel Prize ; }, } @article {pmid29542699, year = {2018}, author = {}, title = {Corrections.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {405}, doi = {10.1038/d41586-018-03073-z}, pmid = {29542699}, issn = {1476-4687}, } @article {pmid29542698, year = {2018}, author = {}, title = {Everyone needs a data-management plan.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {286}, doi = {10.1038/d41586-018-03065-z}, pmid = {29542698}, issn = {1476-4687}, } @article {pmid29542697, year = {2018}, author = {Snyder, JS}, title = {Questioning human neurogenesis.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {315-316}, doi = {10.1038/d41586-018-02629-3}, pmid = {29542697}, issn = {1476-4687}, mesh = {Humans ; *Neurogenesis ; }, } @article {pmid29542696, year = {2018}, author = {}, title = {Huge panda park, cancer test and elephant trophies.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {290-291}, doi = {10.1038/d41586-018-03069-9}, pmid = {29542696}, issn = {1476-4687}, } @article {pmid29542695, year = {2018}, author = {}, title = {How Putin can restore Russian research.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {285-286}, doi = {10.1038/d41586-018-03066-y}, pmid = {29542695}, issn = {1476-4687}, mesh = {*Research ; Russia ; }, } @article {pmid29542694, year = {2018}, author = {Witze, A}, title = {Drilling project probes New Zealand's risk of killer quakes.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {295-296}, doi = {10.1038/d41586-018-02640-8}, pmid = {29542694}, issn = {1476-4687}, } @article {pmid29542693, year = {2018}, author = {Glenn, DR and Bucher, DB and Lee, J and Lukin, MD and Park, H and Walsworth, RL}, title = {High-resolution magnetic resonance spectroscopy using a solid-state spin sensor.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {351-354}, pmid = {29542693}, issn = {1476-4687}, mesh = {Magnetic Resonance Spectroscopy/*instrumentation/*methods ; Metabolomics/methods ; Nitrogen/chemistry ; Single-Cell Analysis/instrumentation/methods ; }, abstract = {Quantum systems that consist of solid-state electronic spins can be sensitive detectors of nuclear magnetic resonance (NMR) signals, particularly from very small samples. For example, nitrogen-vacancy centres in diamond have been used to record NMR signals from nanometre-scale samples, with sensitivity sufficient to detect the magnetic field produced by a single protein. However, the best reported spectral resolution for NMR of molecules using nitrogen-vacancy centres is about 100 hertz. This is insufficient to resolve the key spectral identifiers of molecular structure that are critical to NMR applications in chemistry, structural biology and materials research, such as scalar couplings (which require a resolution of less than ten hertz) and small chemical shifts (which require a resolution of around one part per million of the nuclear Larmor frequency). Conventional, inductively detected NMR can provide the necessary high spectral resolution, but its limited sensitivity typically requires millimetre-scale samples, precluding applications that involve smaller samples, such as picolitre-volume chemical analysis or correlated optical and NMR microscopy. Here we demonstrate a measurement technique that uses a solid-state spin sensor (a magnetometer) consisting of an ensemble of nitrogen-vacancy centres in combination with a narrowband synchronized readout protocol to obtain NMR spectral resolution of about one hertz. We use this technique to observe NMR scalar couplings in a micrometre-scale sample volume of approximately ten picolitres. We also use the ensemble of nitrogen-vacancy centres to apply NMR to thermally polarized nuclear spins and resolve chemical-shift spectra from small molecules. Our technique enables analytical NMR spectroscopy at the scale of single cells.}, } @article {pmid29542692, year = {2018}, author = {Ott, PA and Hu, Z and Keskin, DB and Shukla, SA and Sun, J and Bozym, DJ and Zhang, W and Luoma, A and Giobbie-Hurder, A and Peter, L and Chen, C and Olive, O and Carter, TA and Li, S and Lieb, DJ and Eisenhaure, T and Gjini, E and Stevens, J and Lane, WJ and Javeri, I and Nellaiappan, K and Salazar, AM and Daley, H and Seaman, M and Buchbinder, EI and Yoon, CH and Harden, M and Lennon, N and Gabriel, S and Rodig, SJ and Barouch, DH and Aster, JC and Getz, G and Wucherpfennig, K and Neuberg, D and Ritz, J and Lander, ES and Fritsch, EF and Hacohen, N and Wu, CJ}, title = {Corrigendum: An immunogenic personal neoantigen vaccine for patients with melanoma.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {402}, pmid = {29542692}, issn = {1476-4687}, support = {R50 CA211482/CA/NCI NIH HHS/United States ; }, abstract = {This corrects the article DOI: 10.1038/nature22991.}, } @article {pmid29542691, year = {2018}, author = {Rehfeld, K and Münch, T and Ho, SL and Laepple, T}, title = {Corrigendum: Global patterns of declining temperature variability from the Last Glacial Maximum to the Holocene.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {402}, pmid = {29542691}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature25454.}, } @article {pmid29542690, year = {2018}, author = {Peterson, CW and Benalcazar, WA and Hughes, TL and Bahl, G}, title = {A quantized microwave quadrupole insulator with topologically protected corner states.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {346-350}, pmid = {29542690}, issn = {1476-4687}, abstract = {The theory of electric polarization in crystals defines the dipole moment of an insulator in terms of a Berry phase (geometric phase) associated with its electronic ground state. This concept not only solves the long-standing puzzle of how to calculate dipole moments in crystals, but also explains topological band structures in insulators and superconductors, including the quantum anomalous Hall insulator and the quantum spin Hall insulator, as well as quantized adiabatic pumping processes. A recent theoretical study has extended the Berry phase framework to also account for higher electric multipole moments, revealing the existence of higher-order topological phases that have not previously been observed. Here we demonstrate experimentally a member of this predicted class of materials-a quantized quadrupole topological insulator-produced using a gigahertz-frequency reconfigurable microwave circuit. We confirm the non-trivial topological phase using spectroscopic measurements and by identifying corner states that result from the bulk topology. In addition, we test the critical prediction that these corner states are protected by the topology of the bulk, and are not due to surface artefacts, by deforming the edges of the crystal lattice from the topological to the trivial regime. Our results provide conclusive evidence of a unique form of robustness against disorder and deformation, which is characteristic of higher-order topological insulators.}, } @article {pmid29542689, year = {2018}, author = {Raven, A and Lu, WY and Man, TY and Ferreira-Gonzalez, S and O'Duibhir, E and Dwyer, BJ and Thomson, JP and Meehan, RR and Bogorad, R and Koteliansky, V and Kotelevtsev, Y and Ffrench-Constant, C and Boulter, L and Forbes, SJ}, title = {Corrigendum: Cholangiocytes act as facultative liver stem cells during impaired hepatocyte regeneration.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {402}, pmid = {29542689}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23015.}, } @article {pmid29542688, year = {2018}, author = {Cline Ii, CJ and Faul, UH and David, EC and Berry, AJ and Jackson, I}, title = {Redox-influenced seismic properties of upper-mantle olivine.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {355-358}, pmid = {29542688}, issn = {1476-4687}, abstract = {Lateral variations of seismic wave speeds and attenuation (dissipation of strain energy) in the Earth's upper mantle have the potential to map key characteristics such as temperature, major-element composition, melt fraction and water content. The inversion of these data into meaningful representations of physical properties requires a robust understanding of the micromechanical processes that affect the propagation of seismic waves. Structurally bound water (hydroxyl) is believed to affect seismic properties but this has yet to be experimentally quantified. Here we present a comprehensive low-frequency forced-oscillation assessment of the seismic properties of olivine as a function of water content within the under-saturated regime that is relevant to the Earth's interior. Our results demonstrate that wave speeds and attenuation are in fact strikingly insensitive to water content. Rather, the redox conditions imposed by the choice of metal sleeving, and the associated defect chemistry, appear to have a substantial influence on the seismic properties. These findings suggest that elevated water contents are not responsible for low-velocity or high-attenuation structures in the upper mantle. Instead, the high attenuation observed in hydrous and oxidized regions of the upper mantle (such as above subduction zones) may reflect the prevailing oxygen fugacity. In addition, these data provide no support for the hypothesis whereby a sharp lithosphere-asthenosphere boundary is explained by enhanced grain boundary sliding in the presence of water.}, } @article {pmid29541800, year = {2018}, author = {Li, Y and Zhang, W and Zuo, Y and Zhu, T and Pang, Y and Li, T and Li, Q}, title = {Label-Free Quantitative Proteomic Reveals Differentially Expressed Proteins in Aeromonas-Immunostimulated Leukocytes of Lampetra japonica.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {934-941}, pmid = {29541800}, issn = {1432-0991}, support = {31500106//National Natural Science Foundation of China/ ; L201683674//General Scientific Research Foundation of Liaoning Educational Committee/ ; 2013CB835304//Chinese Major State Basic Research Development Program/ ; 31170353//Chinese National Natural Science Foundation/ ; }, mesh = {Aeromonas/genetics/isolation & purification/*physiology ; Animals ; Chromatography, High Pressure Liquid ; Fish Proteins/*chemistry/genetics/immunology ; Lampreys/*genetics/immunology/*microbiology ; Leukocytes/*chemistry/immunology/microbiology ; Mass Spectrometry ; Proteome/*chemistry/genetics/immunology ; Proteomics ; }, abstract = {Lamprey was considered to be one of the most basal jawless vertebrate representatives for studying vertebrate evolution, embryo development, and the origin of adaptive immunity. Here we investigated the effect of the gut-derived Aeromonas on the lamprey leukocytes proteome using the label-free liquid chromatography-tandem mass spectrometry for quantitative proteomics analysis. Significant difference was observed in the regulation of 34 out of 755 proteins in Aeromonas-immunized lamprey. 31 proteins were only identified in saline solution-immunized lamprey and 47 proteins were only identified in Aeromonas-immunized lamprey. Quantitative real-time polymerase chain reaction was used to validate the results of the proteomic analysis. The differentially expressed proteins were found to be associated with several different biological processes. The identification of leukocytes proteins essential for lamprey adaptive immune response induced by gut-derived Aeromonas strain could supply important information on lamprey-Aeromonas interactions and VLR-based adaptive immune signal pathways.}, } @article {pmid29540570, year = {2018}, author = {Vasseur, F and Exposito-Alonso, M and Ayala-Garay, OJ and Wang, G and Enquist, BJ and Vile, D and Violle, C and Weigel, D}, title = {Adaptive diversification of growth allometry in the plant Arabidopsis thaliana.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3416-3421}, pmid = {29540570}, issn = {1091-6490}, mesh = {*Adaptation, Physiological ; Arabidopsis/genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; *Biological Evolution ; *Climate Change ; Models, Theoretical ; *Stress, Physiological ; }, abstract = {Seed plants vary tremendously in size and morphology; however, variation and covariation in plant traits may be governed, at least in part, by universal biophysical laws and biological constants. Metabolic scaling theory (MST) posits that whole-organismal metabolism and growth rate are under stabilizing selection that minimizes the scaling of hydrodynamic resistance and maximizes the scaling of resource uptake. This constrains variation in physiological traits and in the rate of biomass accumulation, so that they can be expressed as mathematical functions of plant size with near-constant allometric scaling exponents across species. However, the observed variation in scaling exponents calls into question the evolutionary drivers and the universality of allometric equations. We have measured growth scaling and fitness traits of 451 Arabidopsis thaliana accessions with sequenced genomes. Variation among accessions around the scaling exponent predicted by MST was correlated with relative growth rate, seed production, and stress resistance. Genomic analyses indicate that growth allometry is affected by many genes associated with local climate and abiotic stress response. The gene with the strongest effect, PUB4, has molecular signatures of balancing selection, suggesting that intraspecific variation in growth scaling is maintained by opposing selection on the trade-off between seed production and abiotic stress resistance. Our findings suggest that variation in allometry contributes to local adaptation to contrasting environments. Our results help reconcile past debates on the origin of allometric scaling in biology and begin to link adaptive variation in allometric scaling to specific genes.}, } @article {pmid29540569, year = {2018}, author = {Kuser-Abali, G and Gong, L and Yan, J and Liu, Q and Zeng, W and Williamson, A and Lim, CB and Molloy, ME and Little, JB and Huang, L and Yuan, ZM}, title = {An EZH2-mediated epigenetic mechanism behind p53-dependent tissue sensitivity to DNA damage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3452-3457}, pmid = {29540569}, issn = {1091-6490}, support = {R01 CA085679/CA/NCI NIH HHS/United States ; R01 CA125144/CA/NCI NIH HHS/United States ; R01 CA167814/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Chromatin/genetics/*metabolism ; *DNA Damage ; Enhancer of Zeste Homolog 2 Protein/*genetics/metabolism ; *Epigenesis, Genetic ; Mice ; Mice, Transgenic ; Protein Binding ; Proto-Oncogene Proteins/*genetics/metabolism ; Proto-Oncogene Proteins c-mdm2/*genetics/metabolism ; Tumor Suppressor Protein p53/*genetics/metabolism ; Ubiquitination ; }, abstract = {Renewable tissues exhibit heightened sensitivity to DNA damage, which is thought to result from a high level of p53. However, cell proliferation in renewable tissues requires p53 down-regulation, creating an apparent discrepancy between the p53 level and elevated sensitivity to DNA damage. Using a combination of genetic mouse models and pharmacologic inhibitors, we demonstrate that it is p53-regulated MDM2 that functions together with MDMX to regulate DNA damage sensitivity by targeting EZH2 (enhancer of zeste homolog 2) for ubiquitination/degradation. As a methyltransferase, EZH2 promotes H3K27me3, and therefore chromatin compaction, to determine sensitivity to DNA damage. We demonstrate that genetic and pharmacologic interference of the association between MDM2 and MDMX stabilizes EZH2, resulting in protection of renewable tissues from radio-/chemotherapy-induced acute injury. In cells with p53 mutation, there are diminished MDM2 levels, and thus accumulation of EZH2, underpinning the resistant phenotype. Our work uncovers an epigenetic mechanism behind tissue sensitivity to DNA damage, carrying important translation implications.}, } @article {pmid29540568, year = {2018}, author = {Liu, XY and Koba, K and Koyama, LA and Hobbie, SE and Weiss, MS and Inagaki, Y and Shaver, GR and Giblin, AE and Hobara, S and Nadelhoffer, KJ and Sommerkorn, M and Rastetter, EB and Kling, GW and Laundre, JA and Yano, Y and Makabe, A and Yano, M and Liu, CQ}, title = {Nitrate is an important nitrogen source for Arctic tundra plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3398-3403}, pmid = {29540568}, issn = {1091-6490}, mesh = {Denitrification ; Nitrates/*metabolism ; Nitrogen/*analysis ; Plant Leaves/growth & development/*metabolism ; Soil/*chemistry ; *Tundra ; }, abstract = {Plant nitrogen (N) use is a key component of the N cycle in terrestrial ecosystems. The supply of N to plants affects community species composition and ecosystem processes such as photosynthesis and carbon (C) accumulation. However, the availabilities and relative importance of different N forms to plants are not well understood. While nitrate (NO3-) is a major N form used by plants worldwide, it is discounted as a N source for Arctic tundra plants because of extremely low NO3- concentrations in Arctic tundra soils, undetectable soil nitrification, and plant-tissue NO3- that is typically below detection limits. Here we reexamine NO3- use by tundra plants using a sensitive denitrifier method to analyze plant-tissue NO3- Soil-derived NO3- was detected in tundra plant tissues, and tundra plants took up soil NO3- at comparable rates to plants from relatively NO3--rich ecosystems in other biomes. Nitrate assimilation determined by 15N enrichments of leaf NO3- relative to soil NO3- accounted for 4 to 52% (as estimated by a Bayesian isotope-mixing model) of species-specific total leaf N of Alaskan tundra plants. Our finding that in situ soil NO3- availability for tundra plants is high has important implications for Arctic ecosystems, not only in determining species compositions, but also in determining the loss of N from soils via leaching and denitrification. Plant N uptake and soil N losses can strongly influence C uptake and accumulation in tundra soils. Accordingly, this evidence of NO3- availability in tundra soils is crucial for predicting C storage in tundra.}, } @article {pmid29540286, year = {2018}, author = {}, title = {Do you incorporate recent literature or themes from your own research into your genetics courses?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {249-252}, doi = {10.1016/j.tig.2018.02.002}, pmid = {29540286}, issn = {0168-9525}, mesh = {Adult ; Biomedical Research/*education ; Curriculum ; Faculty/*education ; Female ; Genetics/*education ; Humans ; Male ; Periodicals as Topic ; *Textbooks as Topic ; Universities ; }, } @article {pmid29540242, year = {2018}, author = {Lee, JY and Kim, HM and Kim, MJ and Cha, HH and Seong, WJ}, title = {Comparison of single nucleotide polymorphisms in the 3' untranslated region of HLA-G in placentas between spontaneous preterm birth and preeclampsia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {176}, pmid = {29540242}, issn = {1756-0500}, mesh = {3' Untranslated Regions/*genetics ; Adult ; Female ; HLA-G Antigens/*genetics ; Humans ; Placenta/*metabolism ; Polymorphism, Single Nucleotide ; Pre-Eclampsia/*genetics ; Pregnancy ; Premature Birth/*genetics ; }, abstract = {OBJECTIVE: To compare single nucleotide polymorphisms (SNPs) in the 3'-untranslated region (3'UTR) of human leukocyte antigen (HLA)-G in placentas between spontaneous preterm birth and preeclampsia pregnancies.

RESULTS: Placental samples matched for gestational age were obtained from 20 cases of spontaneous preterm births and 19 cases of preeclampsia. Genomic deoxyribonucleic acid was extracted from placenta tissue and the 3'UTR region of HLA-G was amplified via polymerase chain reaction. Nine SNPs were analyzed by direct Sanger sequencing. There was no significant difference in gestational age at delivery or birth weight between two groups. And there were no significant differences in the allele and phenotype frequencies between two groups.}, } @article {pmid29540239, year = {2018}, author = {Sevellec, M and Derome, N and Bernatchez, L}, title = {Holobionts and ecological speciation: the intestinal microbiota of lake whitefish species pairs.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {47}, pmid = {29540239}, issn = {2049-2618}, mesh = {Animals ; Bacteria/*classification/*genetics/isolation & purification ; Base Sequence ; DNA, Bacterial/genetics ; Gastrointestinal Microbiome/*genetics ; Intestines/*microbiology ; Lakes/*microbiology ; RNA, Ribosomal, 16S/genetics ; Salmonidae/*classification/*microbiology ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: It is well established that symbionts have considerable impact on their host, yet the investigation of the possible role of the holobiont in the host's speciation process is still in its infancy. In this study, we compared the intestinal microbiota among five sympatric pairs of dwarf (limnetic) and normal (benthic) lake whitefish Coregonus clupeaformis representing a continuum in the early stage of ecological speciation. We sequenced the 16s rRNA gene V3-V4 regions of the intestinal microbiota present in a total of 108 wild sympatric dwarf and normal whitefish as well as the water bacterial community from five lakes to (i) test for differences between the whitefish intestinal microbiota and the water bacterial community and (ii) test for parallelism in the intestinal microbiota of dwarf and normal whitefish.

RESULTS: The water bacterial community was distinct from the intestinal microbiota, indicating that intestinal microbiota did not reflect the environment, but rather the intrinsic properties of the host microbiota. Our results revealed a strong influence of the host (dwarf or normal) on the intestinal microbiota with pronounced conservation of the core intestinal microbiota (mean ~ 44% of shared genera). However, no clear evidence for parallelism was observed, whereby non-parallel differences between dwarf and normal whitefish were observed in three of the lakes while similar taxonomic composition was observed for the two other species pairs.

CONCLUSIONS: This absence of parallelism across dwarf vs. normal whitefish microbiota highlighted the complexity of the holobiont and suggests that the direction of selection could be different between the host and its microbiota.}, } @article {pmid29540223, year = {2018}, author = {Herath, HMMTB and Pahalagamage, SP and Senanayake, S}, title = {Tongue fasciculations with denervation pattern in osmotic demyelination syndrome: a case report of diagnostic dilemma.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {177}, pmid = {29540223}, issn = {1756-0500}, mesh = {Adult ; *Alcoholism ; Fasciculation/*diagnosis/etiology ; Humans ; Male ; Myelinolysis, Central Pontine/complications/*diagnosis ; Tongue/*innervation/physiopathology ; }, abstract = {BACKGROUND: The pathogenesis of osmotic demyelination syndrome is not completely understood and usually occurs with severe and prolonged hyponatremia, particularly with rapid correction. It can occur even in normonatremic patients, especially who have risk factors like alcoholism, malnutrition and liver disease. Bilateral tongue fasciculations with denervation pattern in electromyogram is a manifestation of damage to the hypoglossal nucleus or hypoglossal nerves. Tongue fasciculations were reported rarely in some cases of osmotic demyelination syndrome, but the exact mechanism is not explained.

CASE PRESENTATION: A 32-year-old Sri Lankan male, with a history of daily alcohol consumption and binge drinking, presented with progressive difficulty in walking, dysphagia, dysarthria and drooling of saliva and alteration of consciousness. On examination he was akinetic and rigid resembling Parkinsonism with a positive Babinski sign. Clinical features were diagnostic of osmotic demyelination syndrome and MRI showed abnormal signal intensity within the central pons and basal ganglia. He also had tongue fasciculations. The electromyogram showed denervation pattern in the tongue with normal findings in the limbs. Medulla and bilateral hypoglossal nerves were normal in MRI.

CONCLUSION: We were unable to explain the exact mechanism for the denervation of the tongue, which resulted in fasciculations in this chronic alcoholic patient who developed osmotic demyelination syndrome. The hypoglossal nuclei are located in the dorsal medulla and radiologically undetected myelinolysis of the medulla is a possibility. Hypoglossal nerve damage caused by methanol or other toxic substances that can contaminate regular ethyl alcohol is another possibility, as it is known to cause neurological and radiological features similar to osmotic demyelination syndrome with long-term exposure. So these toxic substances might play a role in chronic alcoholic patients with central pontine myelinolysis.}, } @article {pmid29540221, year = {2018}, author = {Kiss, DL and Baez, WD and Huebner, K and Bundschuh, R and Schoenberg, DR}, title = {Loss of fragile histidine triad (Fhit) protein expression alters the translation of cancer-associated mRNAs.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {178}, pmid = {29540221}, issn = {1756-0500}, support = {GM084177//National Institute of General Medical Sciences/ ; DMR-1410172//National Science Foundation/ ; U01 CA154200/CA/NCI NIH HHS/United States ; DMR-1105458//National Science Foundation/ ; CA120516//National Cancer Institute/ ; P30 CA016058/CA/NCI NIH HHS/United States ; CA154200//National Cancer Institute/ ; R01 GM084177/GM/NIGMS NIH HHS/United States ; R01 CA120516/CA/NCI NIH HHS/United States ; }, mesh = {Acid Anhydride Hydrolases/*metabolism ; Humans ; Neoplasm Proteins/*metabolism ; Neoplasms/*metabolism ; *Protein Biosynthesis ; RNA, Messenger/*metabolism ; Sequence Analysis, RNA ; }, abstract = {OBJECTIVES: In > 50% of cancers tumor development involves the early loss of Fhit (fragile histidine triad) protein expression, yet the mechanistic pathway(s) by which Fhit mediates its tumor suppressor functions are not fully understood. Earlier attempts to identify a Fhit-deficient gene expression profile relied on total cellular RNA and microarray analysis. The data here used RNA sequencing (RNA-Seq) of Fhit-negative and Fhit-positive cells as proof of principle for the impact of Fhit on specific mRNAs, and to lay the foundation for a study using ribosome profiling to identify mRNAs whose translation is affected by FHIT loss.

DATA DESCRIPTION: RNA-Seq was performed on RNA from lines of Fhit-expressing and Fhit-deficient lung cancer cells. This identified changes in the levels of mRNAs for a number of cell survival and cell cycle progression genes. Polysome profile analysis performed on cytoplasmic extracts from Fhit-negative and Fhit-positive cells showed changes in the sedimentation of select mRNAs consistent with changes in translation efficiency. The impact of differential Fhit expression on the turnover of selected cancer-linked mRNAs was determined by RT-qPCR of cytoplasmic RNA isolated at intervals after treating cells with a transcription inhibitor.}, } @article {pmid29540220, year = {2018}, author = {Sánchez-Carbonel, J and Tantaléan-Yépez, D and Aguilar-Luis, MA and Silva-Caso, W and Weilg, P and Vásquez-Achaya, F and Costa, L and Martins-Luna, J and Sandoval, I and Del Valle-Mendoza, J}, title = {Identification of infection by Chikungunya, Zika, and Dengue in an area of the Peruvian coast. Molecular diagnosis and clinical characteristics.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {175}, pmid = {29540220}, issn = {1756-0500}, support = {Contract 116-PNICP-PIAP-2015//Programa Nacional de Innovación para la Competitividad y Productividad (Innóvate Perú)/ ; }, mesh = {Adolescent ; Adult ; Aged ; Chikungunya Fever/*blood ; Chikungunya virus/*isolation & purification ; Child ; Child, Preschool ; Cross-Sectional Studies ; Dengue/*blood ; Dengue Virus/*isolation & purification ; Humans ; Infant ; Middle Aged ; Peru ; Polymerase Chain Reaction ; Young Adult ; Zika Virus/*isolation & purification ; Zika Virus Infection/*blood ; }, abstract = {OBJECTIVE: To assess the presence of Dengue, Chikungunya, and Zika in serum samples of patients with acute febrile illness in Piura, Peru and describe the most common clinical features.

RESULTS: Dengue was the most common arbovirus detected in 170/496 (34.3%), followed by Zika in 39/496 (7.9%) and Chikungunya in 23/496 (4.6%). Among the 170 samples positive for Dengue, serotype 2 was the most predominant type present in 97/170 (57.1%) of samples, followed by the serotype 3 in 9/170 (5.3%). Headaches, muscle pain, and joint pain were the most common symptoms associated with fever in patients with Dengue and Zika. No symptoms predominance was observed in patients with Chikungunya.Dengue is considered the most frequent arbovirus in Peru and the number of cases has increased dramatically in the last 5 years. However, it is not the only arbovirus that circulates along the northern coast of Peru. It has also been determined the presence of Zika and Chikungunya in our population, which may suggest the circulation of other arboviruses that have not been detected.}, } @article {pmid29540211, year = {2018}, author = {Golassa, L and Tsegaye, A and Erko, B and Mamo, H}, title = {Correction to: High rhesus (Rh(D)) negative frequency and ethnic-group based ABO blood group distribution in Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {180}, pmid = {29540211}, issn = {1756-0500}, abstract = {Following publication of the original article [1] the authors reported that the information in Ref. [32] had been misquoted. The Rh factor in one region in Saudi Arabia is 8.8%, not 29% as stated.}, } @article {pmid29540210, year = {2018}, author = {Ehelepola, NDB and Abayagunawardana, AN and Sudusinghe, TN}, title = {A vegetable-induced hemolytic crisis in a G6PD deficient person: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {179}, pmid = {29540210}, issn = {1756-0500}, mesh = {Acalypha/*adverse effects ; Glucosephosphate Dehydrogenase Deficiency/cerebrospinal fluid/complications/*diagnosis ; *Hemolysis ; Humans ; Male ; Middle Aged ; Vegetables/*adverse effects ; }, abstract = {BACKGROUND: Hemolysis can occur in people with G6PD deficiency under oxidative stress. Acalypha indica is a tropical plant used as a medicinal plant as well as a vegetable. There are a few reported cases of Acalypha indica ingestion induced hemolysis in G6PD deficient people. All except one of them are from Sri Lanka. The information available at present (2017) about G6PD deficiency prevalence and variants of the G6PD gene among Sri Lankans is very sparse. There are no past reports on hemolytic crisis in a G6PD deficient person presenting mimicking leptospirosis.

CASE PRESENTATION: A middle-aged Sri Lankan man presented on the third day of illness complaining of fever, head ache, arthralgia, myalgia, abdominal pain, vomiting, passing dark urine and reduced of urine volume. He gave a history of possible exposure to leptospirosis. He was pale, icteric and his liver was palpable 1 cm below costal margin and there were no other remarkable findings upon physical examination. He had neutrophilic leucocytosis. Leptospirosis was diagnosed. During the second assessment we noticed he was very pale and his urine sample pointed towards hemoglobinuria. Further questioning revealed he had consumed leaves of Acalypha indica as a vegetable. Acute hemolysis in a G6PD deficient patient following Acalypha indica ingestion was diagnosed. Blood transfusions were given to correct his anemia. Later, Brewer's test and quantitative assay of G6PD levels confirmed the diagnosis of G6PD deficiency.

CONCLUSIONS: A hemolytic crisis following oxidative stresses in G6PD deficient patients can present mimicking leptospirosis. Further investigations may reveal why the great majority of cases of acute hemolysis in G6PD deficient person following Acalypha indica ingestion are from Sri Lanka.}, } @article {pmid29540194, year = {2018}, author = {Jia, J and Zhao, P and Cheng, L and Yuan, G and Yang, W and Liu, S and Chen, S and Qi, D and Liu, G and Li, X}, title = {MADS-box family genes in sheepgrass and their involvement in abiotic stress responses.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {42}, pmid = {29540194}, issn = {1471-2229}, mesh = {Gene Expression Regulation, Plant/drug effects ; MADS Domain Proteins/*metabolism ; Oryza/*metabolism ; Phylogeny ; Plant Proteins/*metabolism ; Two-Hybrid System Techniques ; }, abstract = {BACKGROUND: MADS-box genes are categorized into A, B, C, D and E classes and are involved in floral organ identity and flowering. Sheepgrass (Leymus chinensis (Trin.) Tzvel) is an important perennial forage grass and adapts well to many adverse environments. However, there are few studies on the molecular mechanisms of flower development in sheepgrass, especially studies on MADS-domain proteins.

RESULTS: In this study, we cloned 11 MADS-box genes from sheepgrass (Leymus chinensis (Trin.) Tzvel), and phylogenetic analysis of the 11 genes with their homologs revealed that they are divided into nine subclades. Tissue-specific expression profile analysis showed that most of these MADS-box genes were highly expressed in floral organs. LcMADS1 and LcMADS3 showed higher expression in the stamen than in the other tissues, and LcMADS7 showed high expression in the stamen, glume, lemma and palea, while expression of LcMADS2, LcMADS9 and LcMADS11 was higher in vegetative organs than floral organs. Furthermore, yeast two-hybrid analyses showed that LcMADS2 interacted with LcMADS7 and LcMADS9. LcMADS3 interacted with LcMADS4, LcMADS7 and LcMADS10, while LcMADS1 could interact with only LcMADS7. Interestingly, the expression of LcMADS1 and LcMADS2 were significantly induced by cold, and LcMADS9 was significantly up-regulated by NaCl.

CONCLUSION: Hence, we proposed that LcMADS1, LcMADS2, LcMADS3, LcMADS7 and LcMADS9 play a pivotal role in sheepgrass sexual reproduction and may be involved in abiotic stress responses, and our findings provide useful information for further exploration of the functions of this gene family in rice, wheat and other graminaceous cereals.}, } @article {pmid29540192, year = {2018}, author = {Silva Pereira, S and Jackson, AP}, title = {UDP-glycosyltransferase genes in trypanosomatid genomes have diversified independently to meet the distinct developmental needs of parasite adaptations.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {31}, pmid = {29540192}, issn = {1471-2148}, support = {BB/M022811/1//Biotechnology and Biological Sciences Research Council (GB)/International ; Grand Challenges (Round 11)//Bill and Melinda Gates Foundation (US)/International ; }, mesh = {Adaptation, Biological ; Animals ; Euglenozoa Infections/parasitology ; Genome ; Glycosyltransferases/*genetics ; Host-Parasite Interactions ; Humans ; Isoenzymes/genetics ; Phylogeny ; Trypanosomatina/classification/*genetics/physiology ; }, abstract = {BACKGROUND: Trypanosomatid parasites such as Trypanosoma spp. and Leishmania spp. are a major source of infectious disease in humans and domestic animals worldwide. Fundamental to the host-parasite interactions of these potent pathogens are their cell surfaces, which are highly decorated with glycosylated proteins and other macromolecules. Trypanosomatid genomes contain large multi-copy gene families encoding UDP-dependent glycosyltransferases (UGTs), the primary role of which is cell-surface decoration. Here we report a phylogenetic analysis of UGTs from diverse trypanosomatid genomes, the aim of which was to understand the origin and evolution of their diversity.

RESULTS: By combining phylogenetics with analyses of recombination, and selection, we compared UGT repertoire, genomic context and sequence evolution across 19 trypanosomatids. We identified a UGT lineage present in stercorarian trypanosomes and a free-living kinetoplastid Bodo saltans that likely represents the ancestral state of this gene family. The phylogeny of parasite-specific genes shows that UGTs repertoire in Leishmaniinae and salivarian trypanosomes has expanded independently and with distinct evolutionary dynamics. In the former, the ancestral UGT repertoire was organised in a tandem array from which sporadic transpositions to telomeric regions occurred, allowing expansion most likely through telomeric exchange. In the latter, the ancestral UGT repertoire was comprised of seven subtelomeric lineages, two of which have greatly expanded potentially by gene transposition between these dynamic regions of the genome.

CONCLUSIONS: The phylogeny of UGTs confirms that they represent a substantial parasite-specific innovation, which has diversified independently in the distinct trypanosomatid lineages. Nonetheless, developmental regulation has been a strong driver of UGTs diversification in both African trypanosomes and Leishmania.}, } @article {pmid29540172, year = {2018}, author = {Razavi, AM and Khelashvili, G and Weinstein, H}, title = {How structural elements evolving from bacterial to human SLC6 transporters enabled new functional properties.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {31}, pmid = {29540172}, issn = {1741-7007}, support = {U54 GM087519/GM/NIGMS NIH HHS/United States ; R01 DA041510/DA/NIDA NIH HHS/United States ; P01 DA012408/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: Much of the structure-based mechanistic understandings of the function of SLC6A neurotransmitter transporters emerged from the study of their bacterial LeuT-fold homologs. It has become evident, however, that structural differences such as the long N- and C-termini of the eukaryotic neurotransmitter transporters are involved in an expanded set of functional properties to the eukaryotic transporters. These functional properties are not shared by the bacterial homologs, which lack the structural elements that appeared later in evolution. However, mechanistic insights into some of the measured functional properties of the eukaryotic transporters that have been suggested to involve these structural elements are sparse or merely descriptive.

RESULTS: To learn how the structural elements added in evolution enable mechanisms of the eukaryotic transporters in ways not shared with their bacterial LeuT-like homologs, we focused on the human dopamine transporter (hDAT) as a prototype. We present the results of a study employing large-scale molecular dynamics simulations and comparative Markov state model analysis of experimentally determined properties of the wild-type and mutant hDAT constructs. These offer a quantitative outline of mechanisms in which a rich spectrum of interactions of the hDAT N-terminus and C-terminus contribute to the regulation of transporter function (e.g., by phosphorylation) and/or to entirely new phenotypes (e.g., reverse uptake (efflux)) that were added in evolution.

CONCLUSIONS: The findings are consistent with the proposal that the size of eukaryotic neurotransmitter transporter termini increased during evolution to enable more functions (e.g., efflux) not shared with the bacterial homologs. The mechanistic explanations for the experimental findings about the modulation of function in DAT, the serotonin transporter, and other eukaryotic transporters reveal separate roles for the distal and proximal segments of the much larger N-terminus in eukaryotic transporters compared to the bacterial ones. The involvement of the proximal and distal segments - such as the role of the proximal segment in sustaining transport in phosphatidylinositol 4,5-bisphosphate-depleted membranes and of the distal segment in modulating efflux - may represent an evolutionary adaptation required for the function of eukaryotic transporters expressed in various cell types of the same organism that differ in the lipid composition and protein complement of their membrane environment.}, } @article {pmid29540156, year = {2018}, author = {Yang, SJ and Berndl, M and Michael Ando, D and Barch, M and Narayanaswamy, A and Christiansen, E and Hoyer, S and Roat, C and Hung, J and Rueden, CT and Shankar, A and Finkbeiner, S and Nelson, P}, title = {Assessing microscope image focus quality with deep learning.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {77}, pmid = {29540156}, issn = {1471-2105}, support = {R01 NS083390/NS/NINDS NIH HHS/United States ; RF1 AG058476/AG/NIA NIH HHS/United States ; U54 HG008105//National Institutes of Health (US)/International ; R01 NS083390//National Institutes of Health (US)/International ; }, mesh = {Bone Neoplasms/diagnosis ; Diagnostic Imaging/*methods ; Humans ; Image Processing, Computer-Assisted/*methods ; *Machine Learning ; Microscopy/*methods ; Osteosarcoma/*diagnosis ; *Software ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: Large image datasets acquired on automated microscopes typically have some fraction of low quality, out-of-focus images, despite the use of hardware autofocus systems. Identification of these images using automated image analysis with high accuracy is important for obtaining a clean, unbiased image dataset. Complicating this task is the fact that image focus quality is only well-defined in foreground regions of images, and as a result, most previous approaches only enable a computation of the relative difference in quality between two or more images, rather than an absolute measure of quality.

RESULTS: We present a deep neural network model capable of predicting an absolute measure of image focus on a single image in isolation, without any user-specified parameters. The model operates at the image-patch level, and also outputs a measure of prediction certainty, enabling interpretable predictions. The model was trained on only 384 in-focus Hoechst (nuclei) stain images of U2OS cells, which were synthetically defocused to one of 11 absolute defocus levels during training. The trained model can generalize on previously unseen real Hoechst stain images, identifying the absolute image focus to within one defocus level (approximately 3 pixel blur diameter difference) with 95% accuracy. On a simpler binary in/out-of-focus classification task, the trained model outperforms previous approaches on both Hoechst and Phalloidin (actin) stain images (F-scores of 0.89 and 0.86, respectively over 0.84 and 0.83), despite only having been presented Hoechst stain images during training. Lastly, we observe qualitatively that the model generalizes to two additional stains, Hoechst and Tubulin, of an unseen cell type (Human MCF-7) acquired on a different instrument.

CONCLUSIONS: Our deep neural network enables classification of out-of-focus microscope images with both higher accuracy and greater precision than previous approaches via interpretable patch-level focus and certainty predictions. The use of synthetically defocused images precludes the need for a manually annotated training dataset. The model also generalizes to different image and cell types. The framework for model training and image prediction is available as a free software library and the pre-trained model is available for immediate use in Fiji (ImageJ) and CellProfiler.}, } @article {pmid29540154, year = {2018}, author = {Winkler, I and Scheffer, SJ and Lewis, ML and Ottens, KJ and Rasmussen, AP and Gomes-Costa, GA and Huerto Santillan, LM and Condon, MA and Forbes, AA}, title = {Anatomy of a Neotropical insect radiation.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {30}, pmid = {29540154}, issn = {1471-2148}, support = {DEB-1542451//National Science Foundation/International ; DEB-0949361//National Science Foundation/International ; DEB-0330845//National Science Foundation/International ; HRD-9103322//National Science Foundation/International ; DEB-1542269//National Science Foundation/International ; }, mesh = {Animals ; Biodiversity ; Biological Evolution ; Ecology ; Flowers ; Genetic Speciation ; Geography ; Herbivory ; Likelihood Functions ; Phylogeny ; Plants ; Sympatry ; Tephritidae/*classification/*genetics ; }, abstract = {BACKGROUND: Much evolutionary theory predicts that diversity arises via both adaptive radiation (diversification driven by selection against niche-overlap within communities) and divergence of geographically isolated populations. We focus on tropical fruit flies (Blepharoneura, Tephritidae) that reveal unexpected patterns of niche-overlap within local communities. Throughout the Neotropics, multiple sympatric non-interbreeding populations often share the same highly specialized patterns of host use (e.g., flies are specialists on flowers of a single gender of a single species of host plants). Lineage through time (LTT) plots can help distinguish patterns of diversification consistent with ecologically limited adaptive radiation from those predicted by ecologically neutral theories. Here, we use a time-calibrated phylogeny of Blepharoneura to test the hypothesis that patterns of Blepharoneura diversification are consistent with an "ecologically neutral" model of diversification that predicts that diversification is primarily a function of time and space.

RESULTS: The Blepharoneura phylogeny showed more cladogenic divergence associated with geography than with shifts in host-use. Shifts in host-use were associated with ~ 20% of recent splits (< 3 Ma), but > 60% of older splits (> 3 Ma). In the overall tree, gamma statistic and maximum likelihood model fitting showed no evidence of diversification rate changes though there was a weak signature of slowing diversification rate in one of the component clades.

CONCLUSIONS: Overall patterns of Blepharoneura diversity are inconsistent with a traditional explanation of adaptive radiation involving decreases in diversification rates associated with niche-overlap. Sister lineages usually use the same host-species and host-parts, and multiple non-interbreeding sympatric populations regularly co-occur on the same hosts. We suggest that most lineage origins (phylogenetic splits) occur in allopatry, usually without shifts in host-use, and that subsequent dispersal results in assembly of communities composed of multiple sympatric non-interbreeding populations of flies that share the same hosts.}, } @article {pmid29540149, year = {2018}, author = {Chen, T and Ji, D and Tian, S}, title = {Variable-angle epifluorescence microscopy characterizes protein dynamics in the vicinity of plasma membrane in plant cells.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {43}, pmid = {29540149}, issn = {1471-2229}, support = {31530057//National Natural Science Foundation of China/ ; 31672210//National Natural Science Foundation of China/ ; }, mesh = {Arabidopsis/metabolism ; Arabidopsis Proteins/metabolism ; Cell Membrane/*metabolism ; Microscopy, Fluorescence/*methods ; Plant Cells/*metabolism ; }, abstract = {BACKGROUND: The assembly of protein complexes and compositional lipid patterning act together to endow cells with the plasticity required to maintain compositional heterogeneity with respect to individual proteins. Hence, the applications for imaging protein localization and dynamics require high accuracy, particularly at high spatio-temporal level.

RESULTS: We provided experimental data for the applications of Variable-Angle Epifluorescence Microscopy (VAEM) in dissecting protein dynamics in plant cells. The VAEM-based co-localization analysis took penetration depth and incident angle into consideration. Besides direct overlap of dual-color fluorescence signals, the co-localization analysis was carried out quantitatively in combination with the methodology for calculating puncta distance and protein proximity index. Besides, simultaneous VAEM tracking of cytoskeletal dynamics provided more insights into coordinated responses of actin filaments and microtubules. Moreover, lateral motility of membrane proteins was analyzed by calculating diffusion coefficients and kymograph analysis, which represented an alternative method for examining protein motility.

CONCLUSION: The present study presented experimental evidence on illustrating the use of VAEM in tracking and dissecting protein dynamics, dissecting endosomal dynamics, cell structure assembly along with membrane microdomain and protein motility in intact plant cells.}, } @article {pmid29540148, year = {2018}, author = {Vazquez, N and Sanchez, L and Marks, R and Martinez, E and Fanniel, V and Lopez, A and Salinas, A and Flores, I and Hirschmann, J and Gilkerson, R and Schuenzel, E and Dearth, R and Halaby, R and Innis-Whitehouse, W and Keniry, M}, title = {A protocol for custom CRISPR Cas9 donor vector construction to truncate genes in mammalian cells using pcDNA3 backbone.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {3}, pmid = {29540148}, issn = {1471-2199}, support = {UTRGV College of Sciences (COS) Seed Grant//UTRGV COS/International ; NIH 1SC3GM11666901/GM/NIGMS NIH HHS/United States ; USDA H.S.I. 2016-38422-25760//National Institute of Food and Agriculture/International ; 1463991//National Science Foundation/International ; NIH 5R25GM10086606/GM/NIGMS NIH HHS/United States ; USDA Step 2 2015-38422-24061//National Institute of Food and Agriculture/International ; NSF 1463991//National Science Foundation/International ; NSF Advance 1209210//National Science Foundation/International ; HHMI 52007568/HHMI/Howard Hughes Medical Institute/United States ; SC3 GM116669/GM/NIGMS NIH HHS/United States ; }, mesh = {*CRISPR-Cas Systems ; Cell Line ; Deoxyribonuclease I/metabolism ; Forkhead Box Protein O3/*genetics ; Gene Editing/*methods ; Genetic Vectors ; HEK293 Cells ; Homologous Recombination ; Humans ; Male ; Mutation ; Plasmids/*genetics ; RNA, Guide/metabolism ; }, abstract = {BACKGROUND: Clustered regularly interspaced short palindromic repeat (CRISPR) RNA-guided adaptive immune systems are found in prokaryotes to defend cells from foreign DNA. CRISPR Cas9 systems have been modified and employed as genome editing tools in wide ranging organisms. Here, we provide a detailed protocol to truncate genes in mammalian cells using CRISPR Cas9 editing. We describe custom donor vector construction using Gibson assembly with the commonly utilized pcDNA3 vector as the backbone.

RESULTS: We describe a step-by-step method to truncate genes of interest in mammalian cell lines using custom-made donor vectors. Our method employs 2 guide RNAs, mutant Cas9D10A nickase (Cas9 = CRISPR associated sequence 9), and a custom-made donor vector for homologous recombination to precisely truncate a gene of interest with a selectable neomycin resistance cassette (NPTII: Neomycin Phosphotransferase II). We provide a detailed protocol on how to design and construct a custom donor vector using Gibson assembly (and the commonly utilized pcDNA3 vector as the backbone) allowing researchers to obtain specific gene modifications of interest (gene truncation, gene deletion, epitope tagging or knock-in mutation). Selection of mutants in mammalian cell lines with G418 (Geneticin) combined with several screening methods: western blot analysis, polymerase chain reaction, and Sanger sequencing resulted in streamlined mutant isolation. Proof of principle experiments were done in several mammalian cell lines.

CONCLUSIONS: Here we describe a detailed protocol to employ CRISPR Cas9 genome editing to truncate genes of interest using the commonly employed expression vector pcDNA3 as the backbone for the donor vector. Providing a detailed protocol for custom donor vector design and construction will enable researchers to develop unique genome editing tools. To date, detailed protocols for CRISPR Cas9 custom donor vector construction are limited (Lee et al. in Sci Rep 5:8572, 2015; Ma et al. in Sci Rep 4:4489, 2014). Custom donor vectors are commercially available, but can be expensive. Our goal is to share this protocol to aid researchers in performing genetic investigations that require custom donor vectors for specialized applications (specific gene truncations, knock-in mutations, and epitope tagging applications).}, } @article {pmid29539642, year = {2018}, author = {Vandewauw, I and De Clercq, K and Mulier, M and Held, K and Pinto, S and Van Ranst, N and Segal, A and Voet, T and Vennekens, R and Zimmermann, K and Vriens, J and Voets, T}, title = {A TRP channel trio mediates acute noxious heat sensing.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {662-666}, pmid = {29539642}, issn = {1476-4687}, mesh = {Animals ; Burns/physiopathology/prevention & control ; Cold Temperature/adverse effects ; Female ; Hot Temperature/*adverse effects ; Male ; Mice ; Mice, Knockout ; Nerve Endings/physiology ; Nerve Fibers/physiology ; Nociception/physiology ; Nociceptive Pain/*physiopathology ; Sensory Receptor Cells/physiology ; Skin/innervation/physiopathology ; TRPA1 Cation Channel/deficiency/genetics/*metabolism ; TRPM Cation Channels/deficiency/genetics/*metabolism ; TRPV Cation Channels/deficiency/genetics/*metabolism ; Thermosensing/genetics/*physiology ; }, abstract = {Acute pain represents a crucial alarm signal to protect us from injury. Whereas the nociceptive neurons that convey pain signals were described more than a century ago, the molecular sensors that detect noxious thermal or mechanical insults have yet to be fully identified. Here we show that acute noxious heat sensing in mice depends on a triad of transient receptor potential (TRP) ion channels: TRPM3, TRPV1, and TRPA1. We found that robust somatosensory heat responsiveness at the cellular and behavioural levels is observed only if at least one of these TRP channels is functional. However, combined genetic or pharmacological elimination of all three channels largely and selectively prevents heat responses in both isolated sensory neurons and rapidly firing C and Aδ sensory nerve fibres that innervate the skin. Strikingly, Trpv1-/-Trpm3-/-Trpa1-/- triple knockout (TKO) mice lack the acute withdrawal response to noxious heat that is necessary to avoid burn injury, while showing normal nociceptive responses to cold or mechanical stimuli and a preserved preference for moderate temperatures. These findings indicate that the initiation of the acute heat-evoked pain response in sensory nerve endings relies on three functionally redundant TRP channels, representing a fault-tolerant mechanism to avoid burn injury.}, } @article {pmid29539641, year = {2018}, author = {Zhong, S and Zhang, S and Fan, X and Wu, Q and Yan, L and Dong, J and Zhang, H and Li, L and Sun, L and Pan, N and Xu, X and Tang, F and Zhang, J and Qiao, J and Wang, X}, title = {A single-cell RNA-seq survey of the developmental landscape of the human prefrontal cortex.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {524-528}, pmid = {29539641}, issn = {1476-4687}, mesh = {Cell Differentiation/*genetics ; Humans ; Interneurons/cytology/metabolism ; Neural Stem Cells/cytology/metabolism ; Neurogenesis/genetics ; Neurons/classification/cytology/metabolism ; Prefrontal Cortex/*cytology/*embryology ; RNA/*analysis/genetics ; *Sequence Analysis, RNA ; Signal Transduction ; *Single-Cell Analysis ; }, abstract = {The mammalian prefrontal cortex comprises a set of highly specialized brain areas containing billions of cells and serves as the centre of the highest-order cognitive functions, such as memory, cognitive ability, decision-making and social behaviour. Although neural circuits are formed in the late stages of human embryonic development and even after birth, diverse classes of functional cells are generated and migrate to the appropriate locations earlier in development. Dysfunction of the prefrontal cortex contributes to cognitive deficits and the majority of neurodevelopmental disorders; there is therefore a need for detailed knowledge of the development of the prefrontal cortex. However, it is still difficult to identify cell types in the developing human prefrontal cortex and to distinguish their developmental features. Here we analyse more than 2,300 single cells in the developing human prefrontal cortex from gestational weeks 8 to 26 using RNA sequencing. We identify 35 subtypes of cells in six main classes and trace the developmental trajectories of these cells. Detailed analysis of neural progenitor cells highlights new marker genes and unique developmental features of intermediate progenitor cells. We also map the timeline of neurogenesis of excitatory neurons in the prefrontal cortex and detect the presence of interneuron progenitors in early developing prefrontal cortex. Moreover, we reveal the intrinsic development-dependent signals that regulate neuron generation and circuit formation using single-cell transcriptomic data analysis. Our screening and characterization approach provides a blueprint for understanding the development of the human prefrontal cortex in the early and mid-gestational stages in order to systematically dissect the cellular basis and molecular regulation of prefrontal cortex function in humans.}, } @article {pmid29539640, year = {2018}, author = {McQuaid, JB and Kustka, AB and Oborník, M and Horák, A and McCrow, JP and Karas, BJ and Zheng, H and Kindeberg, T and Andersson, AJ and Barbeau, KA and Allen, AE}, title = {Carbonate-sensitive phytotransferrin controls high-affinity iron uptake in diatoms.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {534-537}, pmid = {29539640}, issn = {1476-4687}, mesh = {Aquatic Organisms/classification/genetics/metabolism ; Biological Transport ; Carbonates/*metabolism ; Diatoms/genetics/*metabolism ; Endocytosis ; Evolution, Molecular ; Genome/genetics ; Humans ; Hydrogen-Ion Concentration ; Iron/*metabolism ; Phytoplankton/classification/genetics/metabolism ; Seawater/chemistry ; Transferrin/*metabolism ; }, abstract = {In vast areas of the ocean, the scarcity of iron controls the growth and productivity of phytoplankton. Although most dissolved iron in the marine environment is complexed with organic molecules, picomolar amounts of labile inorganic iron species (labile iron) are maintained within the euphotic zone and serve as an important source of iron for eukaryotic phytoplankton and particularly for diatoms. Genome-enabled studies of labile iron utilization by diatoms have previously revealed novel iron-responsive transcripts, including the ferric iron-concentrating protein ISIP2A, but the mechanism behind the acquisition of picomolar labile iron remains unknown. Here we show that ISIP2A is a phytotransferrin that independently and convergently evolved carbonate ion-coordinated ferric iron binding. Deletion of ISIP2A disrupts high-affinity iron uptake in the diatom Phaeodactylum tricornutum, and uptake is restored by complementation with human transferrin. ISIP2A is internalized by endocytosis, and manipulation of the seawater carbonic acid system reveals a second-order dependence on the concentrations of labile iron and carbonate ions. In P. tricornutum, the synergistic interaction of labile iron and carbonate ions occurs at environmentally relevant concentrations, revealing that carbonate availability co-limits iron uptake. Phytotransferrin sequences have a broad taxonomic distribution and are abundant in marine environmental genomic datasets, suggesting that acidification-driven declines in the concentration of seawater carbonate ions will have a negative effect on this globally important eukaryotic iron acquisition mechanism.}, } @article {pmid29539639, year = {2018}, author = {Capper, D and Jones, DTW and Sill, M and Hovestadt, V and Schrimpf, D and Sturm, D and Koelsche, C and Sahm, F and Chavez, L and Reuss, DE and Kratz, A and Wefers, AK and Huang, K and Pajtler, KW and Schweizer, L and Stichel, D and Olar, A and Engel, NW and Lindenberg, K and Harter, PN and Braczynski, AK and Plate, KH and Dohmen, H and Garvalov, BK and Coras, R and Hölsken, A and Hewer, E and Bewerunge-Hudler, M and Schick, M and Fischer, R and Beschorner, R and Schittenhelm, J and Staszewski, O and Wani, K and Varlet, P and Pages, M and Temming, P and Lohmann, D and Selt, F and Witt, H and Milde, T and Witt, O and Aronica, E and Giangaspero, F and Rushing, E and Scheurlen, W and Geisenberger, C and Rodriguez, FJ and Becker, A and Preusser, M and Haberler, C and Bjerkvig, R and Cryan, J and Farrell, M and Deckert, M and Hench, J and Frank, S and Serrano, J and Kannan, K and Tsirigos, A and Brück, W and Hofer, S and Brehmer, S and Seiz-Rosenhagen, M and Hänggi, D and Hans, V and Rozsnoki, S and Hansford, JR and Kohlhof, P and Kristensen, BW and Lechner, M and Lopes, B and Mawrin, C and Ketter, R and Kulozik, A and Khatib, Z and Heppner, F and Koch, A and Jouvet, A and Keohane, C and Mühleisen, H and Mueller, W and Pohl, U and Prinz, M and Benner, A and Zapatka, M and Gottardo, NG and Driever, PH and Kramm, CM and Müller, HL and Rutkowski, S and von Hoff, K and Frühwald, MC and Gnekow, A and Fleischhack, G and Tippelt, S and Calaminus, G and Monoranu, CM and Perry, A and Jones, C and Jacques, TS and Radlwimmer, B and Gessi, M and Pietsch, T and Schramm, J and Schackert, G and Westphal, M and Reifenberger, G and Wesseling, P and Weller, M and Collins, VP and Blümcke, I and Bendszus, M and Debus, J and Huang, A and Jabado, N and Northcott, PA and Paulus, W and Gajjar, A and Robinson, GW and Taylor, MD and Jaunmuktane, Z and Ryzhova, M and Platten, M and Unterberg, A and Wick, W and Karajannis, MA and Mittelbronn, M and Acker, T and Hartmann, C and Aldape, K and Schüller, U and Buslei, R and Lichter, P and Kool, M and Herold-Mende, C and Ellison, DW and Hasselblatt, M and Snuderl, M and Brandner, S and Korshunov, A and von Deimling, A and Pfister, SM}, title = {DNA methylation-based classification of central nervous system tumours.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {469-474}, pmid = {29539639}, issn = {1476-4687}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; T32 CA163185/CA/NCI NIH HHS/United States ; 5T32CA163185/NH/NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Central Nervous System Neoplasms/classification/*diagnosis/*genetics/pathology ; Child ; Child, Preschool ; Cohort Studies ; *DNA Methylation ; Female ; Humans ; Infant ; Male ; Middle Aged ; Reproducibility of Results ; Unsupervised Machine Learning ; Young Adult ; }, abstract = {Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology.}, } @article {pmid29539638, year = {2018}, author = {Kremling, KAG and Chen, SY and Su, MH and Lepak, NK and Romay, MC and Swarts, KL and Lu, F and Lorant, A and Bradbury, PJ and Buckler, ES}, title = {Dysregulation of expression correlates with rare-allele burden and fitness loss in maize.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {520-523}, pmid = {29539638}, issn = {1476-4687}, mesh = {*Alleles ; Crops, Agricultural/genetics ; Gene Expression Regulation, Plant/*genetics ; Genetic Fitness/*genetics ; Genetic Variation/genetics ; Genome, Plant/genetics ; Genotype ; Linkage Disequilibrium ; Phenotype ; Population Density ; Quantitative Trait Loci/genetics ; RNA, Plant/genetics ; Seeds/genetics ; Sequence Analysis, RNA ; Zea mays/*genetics ; }, abstract = {Here we report a multi-tissue gene expression resource that represents the genotypic and phenotypic diversity of modern inbred maize, and includes transcriptomes in an average of 255 lines in seven tissues. We mapped expression quantitative trait loci and characterized the contribution of rare genetic variants to extremes in gene expression. Some of the new mutations that arise in the maize genome can be deleterious; although selection acts to keep deleterious variants rare, their complete removal is impeded by genetic linkage to favourable loci and by finite population size. Modern maize breeders have systematically reduced the effects of this constant mutational pressure through artificial selection and self-fertilization, which have exposed rare recessive variants in elite inbred lines. However, the ongoing effect of these rare alleles on modern inbred maize is unknown. By analysing this gene expression resource and exploiting the extreme diversity and rapid linkage disequilibrium decay of maize, we characterize the effect of rare alleles and evolutionary history on the regulation of expression. Rare alleles are associated with the dysregulation of expression, and we correlate this dysregulation to seed-weight fitness. We find enrichment of ancestral rare variants among expression quantitative trait loci mapped in modern inbred lines, which suggests that historic bottlenecks have shaped regulation. Our results suggest that one path for further genetic improvement in agricultural species lies in purging the rare deleterious variants that have been associated with crop fitness.}, } @article {pmid29539637, year = {2018}, author = {Kim, SJ and Fernandez-Martinez, J and Nudelman, I and Shi, Y and Zhang, W and Raveh, B and Herricks, T and Slaughter, BD and Hogan, JA and Upla, P and Chemmama, IE and Pellarin, R and Echeverria, I and Shivaraju, M and Chaudhury, AS and Wang, J and Williams, R and Unruh, JR and Greenberg, CH and Jacobs, EY and Yu, Z and de la Cruz, MJ and Mironska, R and Stokes, DL and Aitchison, JD and Jarrold, MF and Gerton, JL and Ludtke, SJ and Akey, CW and Chait, BT and Sali, A and Rout, MP}, title = {Integrative structure and functional anatomy of a nuclear pore complex.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {475-482}, pmid = {29539637}, issn = {1476-4687}, support = {R01 GM080139/GM/NIGMS NIH HHS/United States ; U54 DK107981/DK/NIDDK NIH HHS/United States ; T32 GM008284/GM/NIGMS NIH HHS/United States ; R01 GM083960/GM/NIGMS NIH HHS/United States ; R01 GM080477/GM/NIGMS NIH HHS/United States ; P41 GM103314/GM/NIGMS NIH HHS/United States ; R01 GM112108/GM/NIGMS NIH HHS/United States ; U54 GM103511/GM/NIGMS NIH HHS/United States ; P50 GM076547/GM/NIGMS NIH HHS/United States ; R01 GM063834/GM/NIGMS NIH HHS/United States ; R01 GM045377/GM/NIGMS NIH HHS/United States ; P41 GM109824/GM/NIGMS NIH HHS/United States ; S10 OD021596/OD/NIH HHS/United States ; }, mesh = {Cross-Linking Reagents/chemistry ; Mass Spectrometry ; Models, Molecular ; Nuclear Pore/*chemistry/*metabolism ; Nuclear Pore Complex Proteins/*chemistry/*metabolism ; Protein Stability ; Protein Transport ; RNA Transport ; Saccharomyces cerevisiae/*chemistry ; }, abstract = {Nuclear pore complexes play central roles as gatekeepers of RNA and protein transport between the cytoplasm and nucleoplasm. However, their large size and dynamic nature have impeded a full structural and functional elucidation. Here we determined the structure of the entire 552-protein nuclear pore complex of the yeast Saccharomyces cerevisiae at sub-nanometre precision by satisfying a wide range of data relating to the molecular arrangement of its constituents. The nuclear pore complex incorporates sturdy diagonal columns and connector cables attached to these columns, imbuing the structure with strength and flexibility. These cables also tie together all other elements of the nuclear pore complex, including membrane-interacting regions, outer rings and RNA-processing platforms. Inwardly directed anchors create a high density of transport factor-docking Phe-Gly repeats in the central channel, organized into distinct functional units. This integrative structure enables us to rationalize the architecture, transport mechanism and evolutionary origins of the nuclear pore complex.}, } @article {pmid29539636, year = {2018}, author = {Cusanovich, DA and Reddington, JP and Garfield, DA and Daza, RM and Aghamirzaie, D and Marco-Ferreres, R and Pliner, HA and Christiansen, L and Qiu, X and Steemers, FJ and Trapnell, C and Shendure, J and Furlong, EEM}, title = {The cis-regulatory dynamics of embryonic development at single-cell resolution.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {538-542}, pmid = {29539636}, issn = {1476-4687}, support = {DP1 HG007811/HG/NHGRI NIH HHS/United States ; R01 HG006283/HG/NHGRI NIH HHS/United States ; T32 HL007828/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Differentiation/genetics ; Cell Lineage/genetics ; Chromatin/genetics/metabolism ; Drosophila melanogaster/*cytology/*embryology/genetics ; Embryonic Development/*genetics ; Endoderm/cytology/metabolism ; Enhancer Elements, Genetic/genetics ; Female ; Gastrulation/genetics ; *Gene Expression Regulation, Developmental ; Genome, Insect/genetics ; Male ; Mesoderm/cytology/metabolism ; Organ Specificity/genetics ; Organisms, Genetically Modified/cytology/genetics ; Reproducibility of Results ; *Single-Cell Analysis ; }, abstract = {Understanding how gene regulatory networks control the progressive restriction of cell fates is a long-standing challenge. Recent advances in measuring gene expression in single cells are providing new insights into lineage commitment. However, the regulatory events underlying these changes remain unclear. Here we investigate the dynamics of chromatin regulatory landscapes during embryogenesis at single-cell resolution. Using single-cell combinatorial indexing assay for transposase accessible chromatin with sequencing (sci-ATAC-seq), we profiled chromatin accessibility in over 20,000 single nuclei from fixed Drosophila melanogaster embryos spanning three landmark embryonic stages: 2-4 h after egg laying (predominantly stage 5 blastoderm nuclei), when each embryo comprises around 6,000 multipotent cells; 6-8 h after egg laying (predominantly stage 10-11), to capture a midpoint in embryonic development when major lineages in the mesoderm and ectoderm are specified; and 10-12 h after egg laying (predominantly stage 13), when each of the embryo's more than 20,000 cells are undergoing terminal differentiation. Our results show that there is spatial heterogeneity in the accessibility of the regulatory genome before gastrulation, a feature that aligns with future cell fate, and that nuclei can be temporally ordered along developmental trajectories. During mid-embryogenesis, tissue granularity emerges such that individual cell types can be inferred by their chromatin accessibility while maintaining a signature of their germ layer of origin. Analysis of the data reveals overlapping usage of regulatory elements between cells of the endoderm and non-myogenic mesoderm, suggesting a common developmental program that is reminiscent of the mesendoderm lineage in other species. We identify 30,075 distal regulatory elements that exhibit tissue-specific accessibility. We validated the germ-layer specificity of a subset of these predicted enhancers in transgenic embryos, achieving an accuracy of 90%. Overall, our results demonstrate the power of shotgun single-cell profiling of embryos to resolve dynamic changes in the chromatin landscape during development, and to uncover the cis-regulatory programs of metazoan germ layers and cell types.}, } @article {pmid29539635, year = {2018}, author = {Andersen, TG and Naseer, S and Ursache, R and Wybouw, B and Smet, W and De Rybel, B and Vermeer, JEM and Geldner, N}, title = {Diffusible repression of cytokinin signalling produces endodermal symmetry and passage cells.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {529-533}, pmid = {29539635}, issn = {1476-4687}, mesh = {Arabidopsis/*anatomy & histology/*cytology/growth & development/metabolism ; Arabidopsis Proteins/metabolism ; *Body Patterning ; Cell Differentiation ; Cytokinins/*metabolism ; *Diffusion ; Endoderm/anatomy & histology/*cytology/*metabolism ; Indoleacetic Acids/metabolism ; Meristem/anatomy & histology/cytology/growth & development/metabolism ; Plant Cells/metabolism ; *Signal Transduction ; }, abstract = {In vascular plants, the root endodermis surrounds the central vasculature as a protective sheath that is analogous to the polarized epithelium in animals, and contains ring-shaped Casparian strips that restrict diffusion. After an initial lag phase, individual endodermal cells suberize in an apparently random fashion to produce 'patchy' suberization that eventually generates a zone of continuous suberin deposition. Casparian strips and suberin lamellae affect paracellular and transcellular transport, respectively. Most angiosperms maintain some isolated cells in an unsuberized state as so-called 'passage cells', which have previously been suggested to enable uptake across an otherwise-impermeable endodermal barrier. Here we demonstrate that these passage cells are late emanations of a meristematic patterning process that reads out the underlying non-radial symmetry of the vasculature. This process is mediated by the non-cell-autonomous repression of cytokinin signalling in the root meristem, and leads to distinct phloem- and xylem-pole-associated endodermal cells. The latter cells can resist abscisic acid-dependent suberization to produce passage cells. Our data further demonstrate that, during meristematic patterning, xylem-pole-associated endodermal cells can dynamically alter passage-cell numbers in response to nutrient status, and that passage cells express transporters and locally affect the expression of transporters in adjacent cortical cells.}, } @article {pmid29539634, year = {2018}, author = {Albright, R and Takeshita, Y and Koweek, DA and Ninokawa, A and Wolfe, K and Rivlin, T and Nebuchina, Y and Young, J and Caldeira, K}, title = {Carbon dioxide addition to coral reef waters suppresses net community calcification.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {516-519}, pmid = {29539634}, issn = {1476-4687}, mesh = {Animals ; Anthozoa/drug effects/*metabolism ; Australia ; *Calcification, Physiologic/drug effects ; Calcium/*metabolism ; Calcium Carbonate/chemistry ; Carbon Dioxide/*adverse effects/analysis/*metabolism ; *Coral Reefs ; Hydrogen-Ion Concentration ; Models, Biological ; Seawater/*chemistry ; Time Factors ; }, abstract = {Coral reefs feed millions of people worldwide, provide coastal protection and generate billions of dollars annually in tourism revenue. The underlying architecture of a reef is a biogenic carbonate structure that accretes over many years of active biomineralization by calcifying organisms, including corals and algae. Ocean acidification poses a chronic threat to coral reefs by reducing the saturation state of the aragonite mineral of which coral skeletons are primarily composed, and lowering the concentration of carbonate ions required to maintain the carbonate reef. Reduced calcification, coupled with increased bioerosion and dissolution, may drive reefs into a state of net loss this century. Our ability to predict changes in ecosystem function and associated services ultimately hinges on our understanding of community- and ecosystem-scale responses. Past research has primarily focused on the responses of individual species rather than evaluating more complex, community-level responses. Here we use an in situ carbon dioxide enrichment experiment to quantify the net calcification response of a coral reef flat to acidification. We present an estimate of community-scale calcification sensitivity to ocean acidification that is, to our knowledge, the first to be based on a controlled experiment in the natural environment. This estimate provides evidence that near-future reductions in the aragonite saturation state will compromise the ecosystem function of coral reefs.}, } @article {pmid29539633, year = {2018}, author = {Perez-Garcia, V and Fineberg, E and Wilson, R and Murray, A and Mazzeo, CI and Tudor, C and Sienerth, A and White, JK and Tuck, E and Ryder, EJ and Gleeson, D and Siragher, E and Wardle-Jones, H and Staudt, N and Wali, N and Collins, J and Geyer, S and Busch-Nentwich, EM and Galli, A and Smith, JC and Robertson, E and Adams, DJ and Weninger, WJ and Mohun, T and Hemberger, M}, title = {Placentation defects are highly prevalent in embryonic lethal mouse mutants.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {463-468}, pmid = {29539633}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Embryo Loss/*genetics/*pathology ; Female ; Mice ; Mice, Knockout ; *Mutation ; Placenta/*pathology ; Placentation/*genetics ; Pregnancy ; Stem Cells/metabolism/pathology ; Trophoblasts/metabolism/pathology ; }, abstract = {Large-scale phenotyping efforts have demonstrated that approximately 25-30% of mouse gene knockouts cause intrauterine lethality. Analysis of these mutants has largely focused on the embryo and not the placenta, despite the crucial role of this extraembryonic organ for developmental progression. Here we screened 103 embryonic lethal and sub-viable mouse knockout lines from the Deciphering the Mechanisms of Developmental Disorders program for placental phenotypes. We found that 68% of knockout lines that are lethal at or after mid-gestation exhibited placental dysmorphologies. Early lethality (embryonic days 9.5-14.5) is almost always associated with severe placental malformations. Placental defects correlate strongly with abnormal brain, heart and vascular development. Analysis of mutant trophoblast stem cells and conditional knockouts suggests that a considerable number of factors that cause embryonic lethality when ablated have primary gene function in trophoblast cells. Our data highlight the hugely under-appreciated importance of placental defects in contributing to abnormal embryo development and suggest key molecular nodes that govern placenta formation.}, } @article {pmid29539271, year = {2018}, author = {Franck, CM and Westermann, J and Boisson-Dernier, A}, title = {Plant Malectin-Like Receptor Kinases: From Cell Wall Integrity to Immunity and Beyond.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {301-328}, doi = {10.1146/annurev-arplant-042817-040557}, pmid = {29539271}, issn = {1545-2123}, abstract = {Plant cells are surrounded by cell walls protecting them from a myriad of environmental challenges. For successful habitat adaptation, extracellular cues are perceived at the cell wall and relayed to downstream signaling constituents to mediate dynamic cell wall remodeling and adapted intracellular responses. Plant malectin-like receptor kinases, also known as Catharanthus roseus receptor-like kinase 1-like proteins (CrRLK1Ls), take part in these perception and relay processes. CrRLK1Ls are involved in many different plant functions. Their ligands, interactors, and downstream signaling partners are being unraveled, and studies about CrRLK1Ls' roles in plant species other than the plant model Arabidopsis thaliana are beginning to flourish. This review focuses on recent CrRLK1L-related advances in cell growth, reproduction, hormone signaling, abiotic stress responses, and, particularly, immunity. We also give an overview of the comparative genomics and evolution of CrRLK1Ls, and present a brief outlook for future research.}, } @article {pmid29539270, year = {2018}, author = {Marshall, RS and Vierstra, RD}, title = {Autophagy: The Master of Bulk and Selective Recycling.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {173-208}, doi = {10.1146/annurev-arplant-042817-040606}, pmid = {29539270}, issn = {1545-2123}, abstract = {Plants have evolved sophisticated mechanisms to recycle intracellular constituents, which are essential for developmental and metabolic transitions; for efficient nutrient reuse; and for the proper disposal of proteins, protein complexes, and even entire organelles that become obsolete or dysfunctional. One major route is autophagy, which employs specialized vesicles to encapsulate and deliver cytoplasmic material to the vacuole for breakdown. In the past decade, the mechanics of autophagy and the scores of components involved in autophagic vesicle assembly have been documented. Now emerging is the importance of dedicated receptors that help recruit appropriate cargo, which in many cases exploit ubiquitylation as a signal. Although operating at a low constitutive level in all plant cells, autophagy is upregulated during senescence and various environmental challenges and is essential for proper nutrient allocation. Its importance to plant metabolism and energy balance in particular places autophagy at the nexus of robust crop performance, especially under suboptimal conditions.}, } @article {pmid29539269, year = {2018}, author = {Howe, GA and Major, IT and Koo, AJ}, title = {Modularity in Jasmonate Signaling for Multistress Resilience.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {387-415}, doi = {10.1146/annurev-arplant-042817-040047}, pmid = {29539269}, issn = {1545-2123}, abstract = {The plant hormone jasmonate coordinates immune and growth responses to increase plant survival in unpredictable environments. The core jasmonate signaling pathway comprises several functional modules, including a repertoire of COI1-JAZ (CORONATINE INSENSITIVE1-JASMONATE-ZIM DOMAIN) coreceptors that couple jasmonoyl-l-isoleucine perception to the degradation of JAZ repressors, JAZ-interacting transcription factors that execute physiological responses, and multiple negative feedback loops to ensure timely termination of these responses. Here, we review the jasmonate signaling pathway with an emphasis on understanding how transcriptional responses are specific, tunable, and evolvable. We explore emerging evidence that JAZ proteins integrate multiple informational cues and mediate crosstalk by propagating changes in protein-protein interaction networks. We also discuss recent insights into the evolution of jasmonate signaling and highlight how plant-associated organisms manipulate the pathway to subvert host immunity. Finally, we consider how this mechanistic foundation can accelerate the rational design of jasmonate signaling for improving crop resilience and harnessing the wellspring of specialized plant metabolites.}, } @article {pmid29538644, year = {2018}, author = {Camenzind, T and Hammer, EC and Lehmann, J and Solomon, D and Horn, S and Rillig, MC and Hempel, S}, title = {Arbuscular mycorrhizal fungal and soil microbial communities in African Dark Earths.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy033}, pmid = {29538644}, issn = {1574-6941}, abstract = {The socio-economic values of fertile and carbon-rich Dark Earth soils are well described from the Amazon region. Very recently, Dark Earth soils were also identified in tropical West Africa, with comparable beneficial soil properties and plant growth-promoting effects. The impact of this management technique on soil microbial communities, however, is less well understood, especially with respect to the ecologically relevant group of arbuscular mycorrhizal (AM) fungi. Thus, we tested the hypotheses that (1) improved soil quality in African Dark Earth (AfDE) will increase soil microbial biomass and shift community composition and (2) concurrently increased nutrient availability will negatively affect AM fungal communities. Microbial communities were distinct in AfDE in comparison to adjacent sites, with an increased fungal:bacterial ratio of 71%, a pattern mainly related to shifts in pH. AM fungal abundance and diversity, however, did not differ despite clearly increased soil fertility in AfDE, with 3.7 and 1.7 times greater extractable P and total N content, respectively. The absence of detrimental effects on AM fungi, often seen following applications of inorganic fertilizers, and the enhanced role of saprobic fungi relevant for mineralization and C sequestration support previous assertions of this management type as a sustainable alternative agricultural practice.}, } @article {pmid29537732, year = {2018}, author = {Kennedy, J and Pavličev, M}, title = {Female orgasm and the emergence of prosocial empathy: An evo-devo perspective.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {2}, pages = {66-75}, doi = {10.1002/jez.b.22795}, pmid = {29537732}, issn = {1552-5015}, mesh = {*Biological Evolution ; Coitus/physiology ; Developmental Biology ; Empathy/*genetics/*physiology ; Female ; Humans ; Male ; Orgasm/physiology ; Selection, Genetic ; }, abstract = {In human females, direct or indirect stimulation of the clitoris plays a central role in reaching orgasm. A majority of women report that penetrative coitus alone is insufficient for triggering orgasm, puzzling researchers who expect orgasm to be an outcome of procreative intercourse. In the present paper, we turn our attention to the evolutionary role that such unreliability of orgasm at coitus might have played in human evolution. We emphasize that we do not thereby attempt an explanation of its origin, but its potential evolutionary effect. The present proposal suggests that the variable female orgasm, the position of the clitoris remote from the vagina, and the mismatch of the male refractory period with the female capacity for multiple orgasms, may have contributed to the evolution of human prosocial qualities.}, } @article {pmid29537366, year = {2018}, author = {Liu, MJ and Jin, CZ and Asem, MD and Ju, YJ and Park, DJ and Salam, N and Xiao, M and Li, WJ and Kim, CJ}, title = {Aurantisolimonas haloimpatiens gen. nov., sp. nov., a bacterium isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1552-1559}, doi = {10.1099/ijsem.0.002709}, pmid = {29537366}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain negative, strictly aerobic and non-motile bacterium, designated strain BN130233T, was isolated from a soil sample collected from Gyeongsangbuk-do, Republic of Korea. Colonies were orange in colour, with wet and smooth surfaces. Phylogenetic analyses based on the 16S rRNA gene sequences resulted in strain BN130233T forming a cluster with members of the family Chitinophagaceae Kämpfer et al. 2011, while sharing the highest sequence identity of 91.2 % with Chitinophaga niastensis JS16-4T. Good growth was observed at 20-28 °C, pH 7.0 and in the absence of NaCl. The major fatty acids were summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH. The respiratory quinone was MK-7. Major polar lipids contained phosphatidylethanolamine, an unidentified phospholipid, three unidentified aminolipids and eight unidentified lipids. The genomic DNA G+C content was 40.6 mol%. Phenotypic and chemotaxonomic characteristics together with 16S rRNA gene sequence analyses showed that strain BN130233T was distinct from its close phylogenetic relatives in the family ChitinophagaceaeKämpfer et al. 2011. The strain is, therefore, proposed as a representative of a new genus and new species with the name Aurantisolimonas haloimpatiens. The type strain of Aurantisolimonas haloimpatiens is BN130233T (=CCTCC AB 2017051T=KCTC 42642T).}, } @article {pmid29537365, year = {2018}, author = {Danylec, N and Göbl, A and Stoll, DA and Hetzer, B and Kulling, SE and Huch, M}, title = {Rubneribacter badeniensis gen. nov., sp. nov. and Enteroscipio rubneri gen. nov., sp. nov., new members of the Eggerthellaceae isolated from human faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1533-1540}, doi = {10.1099/ijsem.0.002705}, pmid = {29537365}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Adult ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Feces/*microbiology ; Germany ; Glycolipids/chemistry ; Humans ; Male ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {Two novel, anaerobic, Gram-positive, rod-shaped bacterial strains, ResAG-85T and ResAG-96T, were isolated from a faecal sample of a male human. 16S rRNA gene sequences analyses indicated that these strains represent a distinct lineage within the family Eggerthellaceae. Strain ResAG-85T showed 92.3 % similarity to the type strains of the genera Eggerthella and Gordonibacter. Strain ResAG-96T clustered together with Paraeggerthella hongkongensis and the newly (but not validly) published genus 'Arabia massiliensis' (94.8 % similarity). Analysis of quinones revealed that MK-5 (21 % in ResAG-85T and 95 % in ResAG-96T) and MK-7 (53 % in strain ResAG-85T) were present, which were described for the first time for members of the Eggerthellaceae. Furthermore, MK-6 was present in both strains (25 % ResAG-85T and 5 % in ResAG-96T). The polar lipids detected in ResAG-85T and ResAG-96T consisted of eight and six glycolipids, respectively. Both strains possessed three phospholipids, one phosphatidylglycerol and one diphosphatidylglycerol. Analysis of fatty acids revealed that the percentage of total branched fatty acids was relatively high in comparison to related strains with 42 and 50 % of strains ResAG-85T and ResAG-96T but comparable to the value obtained for Gordonibacter pamelaeae DSM 19378T. On the basis of this polyphasic approach including molecular (16S rRNA gene sequencing) and biochemical methods (analysis of fatty acids, quinones, polar lipids, Rapid ID 32A and API 20A), the new genera and species Rubneribacter badeniensis with ResAG-85T (=DSM 105129T=JCM 32272T) and Enteroscipio rubneri with ResAG-96T (=DSM 105130T=JCM 32273T) as the type and only strains are described.}, } @article {pmid29537363, year = {2018}, author = {Lee, HJ and Whang, KS}, title = {Streptomyces fuscigenes sp. nov., isolated from bamboo (Sasa borealis) litter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1541-1545}, doi = {10.1099/ijsem.0.002706}, pmid = {29537363}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sasa/*microbiology ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Three actinomycetes strains, designated JBL-5, JBL-14 and JBL-20T, were isolated from bamboo (Sasa borealis) litter in Damyang, Republic of Korea. Morphological, chemotaxonomic and phylogenetic analyses demonstrated that the three strains belong to the genus Streptomyces. Microscopic observation revealed that the three strains produced Spirales spore chains with smooth surfaces. Phylogenetic analysis based on 16S rRNA gene sequence comparisons revealed that these strains showed the highest sequence similarity to Streptomyces gelaticus NRRL B-2928T (97.8 %), Streptomyces pulveraceus LMG 20322T (97.7 %), Streptomyces intermedius NBRC 13049T (97.7 %), Streptomyces althioticus NRRL B-3981T (97.7 %) and Streptomyces matensis NBRC 12889T (97.7 %). The DNA-DNA hybridization values between strains JBL-5, JBL-14 and JBL-20T were 91.2-92.4 %, and the values between the three strains and their close phylogenetic relatives were also below 70 %. The predominant menaquinones were MK-9 (H4) and MK-9 (H6). The cell wall contained ll-diaminopimelic acid and the whole-cell sugars were arabinose and xylose. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositolmannoside, two unidentified aminolipids, three unidentified aminophospholipids, one unidentified glycolipid and one unidentified lipid. The major cellular fatty acids were iso-C15 : 0, anteiso-C15 : 0, iso-C14 : 0, C18 : 1ω7c and iso-C16 : 0. The DNA G+C contents were 71.8-72.4 mol%. On the basis of phylogenetic analyses and physiological and biochemical characterization, strains JBL-5, JBL-14 and JBL-20T are considered to represent a novel species of the genus Streptomyces, for which the name Streptomyces fuscigenes sp. nov. is proposed. The type strain is JBL-20T (=KACC 18269T=NBRC 110629T).}, } @article {pmid29537362, year = {2018}, author = {Li, D and Zheng, W and Zhao, J and Han, L and Zhao, X and Jiang, H and Wang, X and Xiang, W}, title = {Lentzea soli sp. nov., an actinomycete isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1496-1501}, doi = {10.1099/ijsem.0.002698}, pmid = {29537362}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A novel actinobacterium, designated strain NEAU-LZC 7T, was isolated from soil collected from Mount Song and characterized using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain NEAU-LZC 7T belonged to the genus Lentzea, with highest sequence similarity to Lentzea violacea JCM 10975T (98.1 %). Morphological and chemotaxonomic characteristics of the strain also supported its assignment to the genus Lentzea. However, DNA-DNA relatedness, physiological and biochemical data showed that strain NEAU-LZC 7T could be distinguished from its closest relative. Therefore, strain NEAU-LZC 7T represents a novel species of the genus Lentzea, for which the name Lentzea soli sp. nov. is proposed, with NEAU-LZC 7T (=CCTCC AA 2017027T=JCM 32384T) as the type strain.}, } @article {pmid29537361, year = {2018}, author = {Thawai, C}, title = {Amycolatopsis rhizosphaerae sp. nov., isolated from rice rhizosphere soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1546-1551}, doi = {10.1099/ijsem.0.002704}, pmid = {29537361}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Oryza/*microbiology ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, designated strain DH51B-4-3T, which formed long chains of spherical spores borne on the tip of sporophores arising from the aerial mycelium, was isolated from rice rhizosphere soil. The isolate contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The whole-cell sugars of strain DH51B-4-3T were arabinose, galactose, glucose, rhamnose and ribose. The phospholipids in the cell membrane were phosphatidylethanolamine, phosphatidyl methylethanolamine, diphosphatidylglycerol and phosphatidylinositol. The major menaquinone was MK-9(H4). The main cellular fatty acids were iso-C16 : 0 and cyclo-C17 : 0. The G+C content of the genomic DNA was 68.2 mol%. Phylogenetic analysis using 16S rRNA gene sequences revealed that strain DH51B-4-3T should be classified in the genus Amycolatopsis and closely related to Amycolatopsis dongchuanensis YIM 75904T (98.06 %) and Amycolatopsis sacchari DSM 44468T (97.77 %). The result of DNA-DNA hybridization and some physiological and biochemical properties indicated that strain DH51B-4-3T could be readily distinguished from its closest phylogenetic relatives. On the basis of these phenotypic and genotypic data, this strain represents a novel species, for which the name Amycolatopsis rhizosphaerae sp. nov. is proposed. The type strain is DH51B-4-3T (=TBRC 6029T=NBRC 112509T).}, } @article {pmid29537360, year = {2018}, author = {Dahal, RH and Kim, J}, title = {Altererythrobacter fulvus sp. nov., a novel alkalitolerant alphaproteobacterium isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1502-1508}, doi = {10.1099/ijsem.0.002697}, pmid = {29537360}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A novel α-proteobacterium, designated strain S-54T, was isolated from forest soil sampled at Kyonggi University and subjected to polyphasic study. Cells were aerobic, Gram-stain-negative, catalase- and oxidase-positive, non-motile, non-spore-forming, rod-shaped and yellow-pigmented. Flexirubin-type pigments were absent. Strain S-54T assimilated lactic acid, d-glucose and 4-hydroxybenzoic acid. Strain S-54T tolerated 4 % NaCl (w/v), and grew optimally at 45 °C and pH 10.5. Phylogenetic analysis based on 16S rRNA gene sequence data revealed that strain S-54T formed a lineage within the class Alphaproteobacteria of the phylum Proteobacteria that was distinct from various members of the genus Altererythrobacter, including Altererythrobacter troitsensis JCM 17037T (96.8 % sequence similarity), Altererythrobacterxinjiangensis S3-63T (96.6 %), Altererythrobacter dongtanensis KCTC 22672T (96.5 %) and Altererythrobacter mangrovi C9-11T (96.5 %). Q-10 was the sole isoprenoid quinone. The major polar lipids were phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and sphingoglycolipid. The major cellular fatty acids were C18 : 1ω7c, C16 : 0 and C18 : 1ω7c 11-methyl. The DNA G+C content of strain S-54T was 64.2 mol%. On the basis of the results of phenotypic, genotypic, chemotaxonomic and phylogenetic analysis, strain S-54T represents a novel species in the genus Altererythrobacter, for which the name Altererythrobacter fulvus sp. nov. is proposed. The type strain of Altererythrobacter fulvus is S-54T (=KEMB 9005-542T=KACC 19119T=NBRC 112676T).}, } @article {pmid29537359, year = {2018}, author = {Park, M and Song, J and Nam, GG and Kim, S and Joung, Y and Cho, JC}, title = {Flavobacterium lacicola sp. nov., isolated from a freshwater lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1565-1570}, doi = {10.1099/ijsem.0.002712}, pmid = {29537359}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Lakes/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A bacterial strain, designated IMCC25901T, was isolated from a freshwater lake, Soyang, in the Republic of Korea. The strain was Gram-stain-negative, aerobic, non-motile, orange-coloured and short rod-shaped. The 16S rRNA gene sequence analysis showed that strain IMCC25901T was most closely related to Flavobacterium yonginense HMD1001T (97.0 %) and formed a robust phylogenetic clade with other species of the genus Flavobacterium. Growth of strain IMCC25901T was observed at 10-30 °C (optimum, 20 °C), pH 6-8 (optimum, pH 7) and 0-1.0 % NaCl (optimum, 0 %). The DNA G+C content of strain IMCC25901T was 34.2 mol%. The major fatty acid constituents of the strain were anteiso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and iso-C15 : 0. Cells of strain IMCC25901T contained phosphatidylethanolamine, an unidentified phospholipid, two unidentified aminolipids and two unidentified lipids. The isoprenoid quinone detected in the strain was MK-6. On the basis of the taxonomic data obtained in this study, it was concluded that strain IMCC25901T represented a novel species in the genus Flavobacterium, for which the name Flavobacterium lacicola sp. nov. is proposed. The type strain of Flavobacterium lacicola is IMCC25901T (=KCTC 52571T=NBRC 112883T).}, } @article {pmid29536825, year = {2018}, author = {Tripathi, KP and Piccirillo, M and Guarracino, MR}, title = {An integrated approach to infer cross-talks between intracellular protein transport and signaling pathways.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 2}, pages = {58}, pmid = {29536825}, issn = {1471-2105}, abstract = {BACKGROUND: The endomembrane system, known as secretory pathway, is responsible for the synthesis and transport of protein molecules in cells. Therefore, genes involved in the secretory pathway are essential for the cellular development and function. Recent scientific investigations show that ER and Golgi apparatus may provide a convenient drug target for cancer therapy. On the other hand, it is known that abundantly expressed genes in different cellular organelles share interconnected pathways and co-regulate each other activities. The cross-talks among these genes play an important role in signaling pathways, associated to the regulation of intracellular protein transport.

RESULTS: In the present study, we device an integrated approach to understand these complex interactions. We analyze gene perturbation expression profiles, reconstruct a directed gene interaction network and decipher the regulatory interactions among genes involved in protein transport signaling. In particular, we focus on expression signatures of genes involved in the secretory pathway of MCF7 breast cancer cell line. Furthermore, network biology analysis delineates these gene-centric cross-talks at the level of specific modules/sub-networks, corresponding to different signaling pathways.

CONCLUSIONS: We elucidate the regulatory connections between genes constituting signaling pathways such as PI3K-Akt, Ras, Rap1, calcium, JAK-STAT, EFGR and FGFR signaling. Interestingly, we determine some key regulatory cross-talks between signaling pathways (PI3K-Akt signaling and Ras signaling pathway) and intracellular protein transport.}, } @article {pmid29536824, year = {2018}, author = {Chebouba, L and Miannay, B and Boughaci, D and Guziolowski, C}, title = {Discriminate the response of Acute Myeloid Leukemia patients to treatment by using proteomics data and Answer Set Programming.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 2}, pages = {59}, pmid = {29536824}, issn = {1471-2105}, abstract = {BACKGROUND: During the last years, several approaches were applied on biomedical data to detect disease specific proteins and genes in order to better target drugs. It was shown that statistical and machine learning based methods use mainly clinical data and improve later their results by adding omics data. This work proposes a new method to discriminate the response of Acute Myeloid Leukemia (AML) patients to treatment. The proposed approach uses proteomics data and prior regulatory knowledge in the form of networks to predict cancer treatment outcomes by finding out the different Boolean networks specific to each type of response to drugs. To show its effectiveness we evaluate our method on a dataset from the DREAM 9 challenge.

RESULTS: The results are encouraging and demonstrate the benefit of our approach to distinguish patient groups with different response to treatment. In particular each treatment response group is characterized by a predictive model in the form of a signaling Boolean network. This model describes regulatory mechanisms which are specific to each response group. The proteins in this model were selected from the complete dataset by imposing optimization constraints that maximize the difference in the logical response of the Boolean network associated to each group of patients given the omic dataset. This mechanistic and predictive model also allow us to classify new patients data into the two different patient response groups.

CONCLUSIONS: We propose a new method to detect the most relevant proteins for understanding different patient responses upon treatments in order to better target drugs using a Prior Knowledge Network and proteomics data. The results are interesting and show the effectiveness of our method.}, } @article {pmid29536823, year = {2018}, author = {Giordano, M and Tripathi, KP and Guarracino, MR}, title = {Ensemble of rankers for efficient gene signature extraction in smoke exposure classification.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 2}, pages = {48}, pmid = {29536823}, issn = {1471-2105}, abstract = {BACKGROUND: System toxicology aims at understanding the mechanisms used by biological systems to respond to toxicants. Such understanding can be leveraged to assess the risk of chemicals, drugs, and consumer products in living organisms. In system toxicology, machine learning techniques and methodologies are applied to develop prediction models for classification of toxicant exposure of biological systems. Gene expression data (RNA/DNA microarray) are often used to develop such prediction models.

RESULTS: The outcome of the present work is an experimental methodology to develop prediction models, based on robust gene signatures, for the classification of cigarette smoke exposure and cessation in humans. It is a result of the participation in the recent sbv IMPROVER SysTox Computational Challenge. By merging different gene selection techniques, we obtain robust gene signatures and we investigate prediction capabilities of different off-the-shelf machine learning techniques, such as artificial neural networks, linear models and support vector machines. We also predict six novel genes in our signature, and firmly believe these genes have to be further investigated as biomarkers for tobacco smoking exposure.

CONCLUSIONS: The proposed methodology provides gene signatures with top-ranked performances in the prediction of the investigated classification methods, as well as new discoveries in genetic signatures for bio-markers of the smoke exposure of humans.}, } @article {pmid29536822, year = {2018}, author = {Fioravanti, D and Giarratano, Y and Maggio, V and Agostinelli, C and Chierici, M and Jurman, G and Furlanello, C}, title = {Phylogenetic convolutional neural networks in metagenomics.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 2}, pages = {49}, pmid = {29536822}, issn = {1471-2105}, abstract = {BACKGROUND: Convolutional Neural Networks can be effectively used only when data are endowed with an intrinsic concept of neighbourhood in the input space, as is the case of pixels in images. We introduce here Ph-CNN, a novel deep learning architecture for the classification of metagenomics data based on the Convolutional Neural Networks, with the patristic distance defined on the phylogenetic tree being used as the proximity measure. The patristic distance between variables is used together with a sparsified version of MultiDimensional Scaling to embed the phylogenetic tree in a Euclidean space.

RESULTS: Ph-CNN is tested with a domain adaptation approach on synthetic data and on a metagenomics collection of gut microbiota of 38 healthy subjects and 222 Inflammatory Bowel Disease patients, divided in 6 subclasses. Classification performance is promising when compared to classical algorithms like Support Vector Machines and Random Forest and a baseline fully connected neural network, e.g. the Multi-Layer Perceptron.

CONCLUSION: Ph-CNN represents a novel deep learning approach for the classification of metagenomics data. Operatively, the algorithm has been implemented as a custom Keras layer taking care of passing to the following convolutional layer not only the data but also the ranked list of neighbourhood of each sample, thus mimicking the case of image data, transparently to the user.}, } @article {pmid29536136, year = {2018}, author = {Rabyk, M and Yushchuk, O and Rokytskyy, I and Anisimova, M and Ostash, B}, title = {Genomic Insights into Evolution of AdpA Family Master Regulators of Morphological Differentiation and Secondary Metabolism in Streptomyces.}, journal = {Journal of molecular evolution}, volume = {86}, number = {3-4}, pages = {204-215}, pmid = {29536136}, issn = {1432-1432}, support = {BG-41Nr//Ministry of Education and Science of Ukraine/ ; }, abstract = {The AdpA protein from a streptomycin producer Streptomyces griseus is a founding member of the AdpA family of pleiotropic regulators, known to be ubiquitously present in streptomycetes. Functional genomic approaches revealed a huge number of AdpA targets, leading to the claim that the AdpA regulon is the largest one in bacteria. The expression of adpA is limited at the level of translation of the rare leucyl UUA codon. All known properties of AdpA regulators were discovered on a few streptomycete strains. There are open questions about the true abundance and diversity of AdpA across actinobacterial taxa (and beyond) and about the possible evolutionary forces that shape the AdpA orthologous group in Streptomyces. Here we show that, with respect to the TTA codon, streptomycete adpA is more diverse than has been previously thought, as the genes differ in presence/position of this codon. Reciprocal best hits to AdpA can be found in many actinobacterial orders, with a domain organization resembling that of the prototypical AdpA, but other configurations also exist. Diversifying positive selection was detected within the DNA-binding (AraC) domain in adpA of Streptomyces origin, most likely affecting residues enabling AdpA to recognize a degenerate operator. Sequence coding for putative glutamine amidotransferase (GATase-1) domain also shows signs of positive selection. The two-domain organization of AdpA most likely arose from a fusion of genes encoding separate GATase-1 and AraC domains. Indeed, we show that the AraC domain retains a biological function in the absence of the GATase-1 part. We suggest that acquisition of the regulatory role by TTA codon is a relatively recent event in the evolution of AdpA, which coincided with the rise of the Streptomycetales clade and, at present, is under relaxed selective constraints. Further experimental scrutiny of our findings is invited, which should provide new insights into the evolution and prospects for engineering of an AdpA-centered regulatory network.}, } @article {pmid29536113, year = {2018}, author = {Valdehuesa, KNG and Ramos, KRM and Moron, LS and Lee, I and Nisola, GM and Lee, WK and Chung, WJ}, title = {Draft Genome Sequence of Newly Isolated Agarolytic Bacteria Cellulophaga omnivescoria sp. nov. W5C Carrying Several Gene Loci for Marine Polysaccharide Degradation.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {925-933}, pmid = {29536113}, issn = {1432-0991}, support = {2015H1D3A1062172//National Research Foundation of Korea/ ; 2016R1C1B1013252//National Research Foundation of Korea/ ; 2009-0093816//National Research Foundation of Korea/ ; }, mesh = {Biodegradation, Environmental ; Flavobacteriaceae/classification/genetics/isolation & purification/*metabolism ; *Genome, Bacterial ; Phylogeny ; Polysaccharides/*metabolism ; Republic of Korea ; Seawater/chemistry/*microbiology ; Sepharose/*metabolism ; }, abstract = {The continued research in the isolation of novel bacterial strains is inspired by the fact that native microorganisms possess certain desired phenotypes necessary for recombinant microorganisms in the biotech industry. Most studies have focused on the isolation and characterization of strains from marine ecosystems as they present a higher microbial diversity than other sources. In this study, a marine bacterium, W5C, was isolated from red seaweed collected from Yeosu, South Korea. The isolate can utilize several natural polysaccharides such as agar, alginate, carrageenan, and chitin. Genome sequence and comparative genomics analyses suggest that strain W5C belongs to a novel species of the Cellulophaga genus, from which the name Cellulophaga omnivescoria sp. nov. is proposed. Its genome harbors 3,083 coding sequences and 146 carbohydrate-active enzymes (CAZymes). Compared to other reported Cellulophaga species, the genome of W5C contained a higher proportion of CAZymes (4.7%). Polysaccharide utilization loci (PUL) for agar, alginate, and carrageenan were identified in the genome, along with other several putative PULs. These PULs are excellent sources for discovering novel hydrolytic enzymes and pathways with unique characteristics required for biorefinery applications, particularly in the utilization of marine renewable biomass. The type strain is JCM 32108T (= KCTC 13157BPT).}, } @article {pmid29535449, year = {2018}, author = {Martin, WF}, title = {Eukaryote lateral gene transfer is Lamarckian.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {754}, doi = {10.1038/s41559-018-0521-7}, pmid = {29535449}, issn = {2397-334X}, } @article {pmid29535448, year = {2018}, author = {Roger, AJ}, title = {Reply to 'Eukaryote lateral gene transfer is Lamarckian'.}, journal = {Nature ecology & evolution}, volume = {2}, number = {5}, pages = {755}, doi = {10.1038/s41559-018-0522-6}, pmid = {29535448}, issn = {2397-334X}, } @article {pmid29535255, year = {2018}, author = {Powell, D}, title = {Core Concept: Mechanical metamaterials bend the rules of everyday physics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2545-2547}, pmid = {29535255}, issn = {1091-6490}, } @article {pmid29535254, year = {2018}, author = {Woo, M}, title = {Inner Workings: Better sequencing tech may help keep planets clean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2542-2544}, doi = {10.1073/pnas.1802808115}, pmid = {29535254}, issn = {1091-6490}, mesh = {*Containment of Biohazards ; *Environmental Microbiology ; Equipment Contamination/*prevention & control ; Exobiology ; Genome, Bacterial/genetics ; Genomics ; Planets ; *Sequence Analysis, DNA ; Spacecraft/*standards ; *Sterilization ; }, } @article {pmid29535226, year = {2018}, author = {Li Volti, G and Polosa, R and Caruso, M}, title = {Assessment of E-cigarette impact on smokers: The importance of experimental conditions relevant to human consumption.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3073-E3074}, pmid = {29535226}, issn = {1091-6490}, mesh = {*Electronic Nicotine Delivery Systems ; Humans ; *Smokers ; Smoking Cessation ; Smoking Prevention ; }, } @article {pmid29535225, year = {2018}, author = {Tang, MS}, title = {Reply to Li Volti et al.: E-cigarette smoke exposure and effect in mice and human cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3075-E3076}, pmid = {29535225}, issn = {1091-6490}, mesh = {Animals ; *Electronic Nicotine Delivery Systems ; Humans ; Lung ; Mice ; Mice, Inbred C57BL ; *Smoke ; Smoking ; Tobacco ; }, } @article {pmid29535224, year = {2018}, author = {Ballesteros-Cánovas, JA and Trappmann, D and Madrigal-González, J and Eckert, N and Stoffel, M}, title = {Climate warming enhances snow avalanche risk in the Western Himalayas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3410-3415}, pmid = {29535224}, issn = {1091-6490}, abstract = {Ongoing climate warming has been demonstrated to impact the cryosphere in the Indian Himalayas, with substantial consequences for the risk of disasters, human well-being, and terrestrial ecosystems. Here, we present evidence that the warming observed in recent decades has been accompanied by increased snow avalanche frequency in the Western Indian Himalayas. Using dendrogeomorphic techniques, we reconstruct the longest time series (150 y) of the occurrence and runout distances of snow avalanches that is currently available for the Himalayas. We apply a generalized linear autoregressive moving average model to demonstrate linkages between climate warming and the observed increase in the incidence of snow avalanches. Warming air temperatures in winter and early spring have indeed favored the wetting of snow and the formation of wet snow avalanches, which are now able to reach down to subalpine slopes, where they have high potential to cause damage. These findings contradict the intuitive notion that warming results in less snow, and thus lower avalanche activity, and have major implications for the Western Himalayan region, an area where human pressure is constantly increasing. Specifically, increasing traffic on a steadily expanding road network is calling for an immediate design of risk mitigation strategies and disaster risk policies to enhance climate change adaption in the wider study region.}, } @article {pmid29535223, year = {2018}, author = {Wang, W and Sijacic, P and Xu, P and Lian, H and Liu, Z}, title = {Arabidopsis TSO1 and MYB3R1 form a regulatory module to coordinate cell proliferation with differentiation in shoot and root.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3045-E3054}, pmid = {29535223}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*growth & development/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; *Cell Differentiation ; *Cell Proliferation ; DNA, Plant ; *Gene Expression Regulation, Plant ; Phenotype ; Plant Roots/*cytology/metabolism ; Plant Shoots/*cytology/metabolism ; Trans-Activators/genetics/*metabolism ; }, abstract = {Fundamental to plant and animal development is the regulated balance between cell proliferation and differentiation, a process intimately tied to cell cycle regulation. In Arabidopsis, mutations in TSO1, whose animal homolog is LIN54, resulted in severe developmental abnormalities both in shoot and root, including shoot meristem fasciation and reduced root meristematic zone. The molecular mechanism that could explain the tso1 mutant phenotype is absent. Through a genetic screen, we identified 32 suppressors that map to the MYB3R1 gene, encoding a conserved cell cycle regulator. Further analysis indicates that TSO1 transcriptionally represses MYB3R1, and the ectopic MYB3R1 activity mediates the tso1 mutant phenotype. Since animal homologs of TSO1 and MYB3R1 are components of a cell cycle regulatory complex, the DREAM complex, we tested and showed that TSO1 and MYB3R1 coimmunoprecipitated in tobacco leaf cells. Our work reveals a conserved cell cycle regulatory module, consisting of TSO1 and MYB3R1, for proper plant development.}, } @article {pmid29535031, year = {2018}, author = {Vinnikov, KA and Thomson, RC and Munroe, TA}, title = {Revised classification of the righteye flounders (Teleostei: Pleuronectidae) based on multilocus phylogeny with complete taxon sampling.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {147-162}, doi = {10.1016/j.ympev.2018.03.014}, pmid = {29535031}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Flounder/*classification/*genetics ; *Genetic Loci ; Geography ; Likelihood Functions ; *Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Members of the family Pleuronectidae are common representatives of the marine benthic fauna inhabiting northern regions of the Atlantic and Pacific oceans. The most recent comprehensive classification of the family, based entirely on morphological synapomorphies, recognized five subfamilies, 23 genera, and 61 extant species. However, several subsequent molecular studies have shown that many synapomorphic characters discovered in the morphological study might represent homoplasies, thereby questioning the reliance on these characters with the warning that they may provide misleading information for testing other morphology-based evolutionary hypotheses. In the present study, we propose a comprehensive taxonomic reassessment of the family Pleuronectidae based on the molecular phylogeny reconstructed from four nuclear and three mitochondrial loci and represented by complete taxon sampling of all but one valid species currently assigned to this family. To check for robustness of the phylogenetic hypothesis, we analyzed the effect of base compositional heterogeneity on phylogenetic signal for each locus and compared six different gene partitioning schemes. The final dataset, comprising 14 partitions and 154 individuals, was used to reconstruct phylogenetic trees in RAxML, MrBayes and BEAST2. Alternative topologies for several questionable nodes were compared using Bayes factors. The topology with the highest marginal likelihood was selected as the final phylogenetic tree for inferring pleuronectid relationships and character evolution. Based on our results, we recognize the Pleuronectidae comprising five subfamilies, 24 genera and 59 species. Our new phylogeny comprises five major monophyletic groups within the family, which we define as the subfamilies within the family: Atheresthinae, Pleuronichthyinae, Microstominae, Hippoglossinae and Pleuronectinae. Taxonomic composition of most of these subfamilies is different from that proposed in previous classifications. We also re-assess hypotheses proposed in earlier studies regarding intra-relationships of species of each lineage. Results of the current study contribute to better understanding of the evolutionary relationships of pleuronectid flatfishes based on molecular evidence, and they also provide the framework towards future comprehensive morphological revision of constituent lineages within the family Pleuronectidae.}, } @article {pmid29535030, year = {2018}, author = {Uva, V and Päckert, M and Cibois, A and Fumagalli, L and Roulin, A}, title = {Comprehensive molecular phylogeny of barn owls and relatives (Family: Tytonidae), and their six major Pleistocene radiations.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {127-137}, doi = {10.1016/j.ympev.2018.03.013}, pmid = {29535030}, issn = {1095-9513}, mesh = {Animals ; Australasia ; Bayes Theorem ; *Fossils ; Geography ; Likelihood Functions ; *Phylogeny ; Strigiformes/*classification/genetics ; Time Factors ; }, abstract = {The owl family Tytonidae comprises two genera: Phodilus, limited to the forests of central Africa and South-East Asia, and the ubiquitous Tyto. The genus Tyto is majorly represented by the cosmopolitan Common Barn Owl group, with more than 30 subspecies worldwide. Discrete differences in body size and plumage colouration have led to the classification of this family into many species and subspecies, but the taxonomic status and phylogenetic relationships between taxa remain unclear, and in some groups controversial. Although several previous studies attempted to resolve this problem, they have been limited in their taxonomic and geographical coverage, or have relied on restricted molecular evidence and low sample sizes. Based on the most comprehensive sampling to date (16 out of 17 Tyto species, and one out of three Phodilus species), a multi-locus approach using seven mitochondrial and two nuclear markers, and taking advantage of field data and museum collections available worldwide, our main questions in this study were: (1) what are the phylogenetic relationships and classification status of the whole family; (2) when and where did the most important speciation events occur? We confirm that the Common Barn Owl, Tyto alba is divided into three main evolutionary units: the American Barn Owl, T. furcata; the Western Barn Owl, T. alba; and the Eastern Barn Owl, T. javanica, and suggest a Late Miocene (ca. 6 mya) Australasian and African origin of the group. Our results are supported by fossil age information, given that the most recent common ancestor between the Tytonidae genera Phodilus and Tyto was probably from the Oligocene (ca. 28 mya) of Australasia. We finally reveal six major Pleistocene radiations of Tyto, all resulting in wide-range distributions.}, } @article {pmid29534854, year = {2018}, author = {Xue, KS and Moncla, LH and Bedford, T and Bloom, JD}, title = {Within-Host Evolution of Human Influenza Virus.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {781-793}, pmid = {29534854}, issn = {1878-4380}, support = {R01 AI127893/AI/NIAID NIH HHS/United States ; R01 GM102198/GM/NIGMS NIH HHS/United States ; T32 AI083203/AI/NIAID NIH HHS/United States ; }, abstract = {The rapid global evolution of influenza virus begins with mutations that arise de novo in individual infections, but little is known about how evolution occurs within hosts. We review recent progress in understanding how and why influenza viruses evolve within human hosts. Advances in deep sequencing make it possible to measure within-host genetic diversity in both acute and chronic influenza infections. Factors like antigenic selection, antiviral treatment, tissue specificity, spatial structure, and multiplicity of infection may affect how influenza viruses evolve within human hosts. Studies of within-host evolution can contribute to our understanding of the evolutionary and epidemiological factors that shape influenza virus's global evolution.}, } @article {pmid29534763, year = {2018}, author = {Dao-Tran, TH and Seib, C and Jones, L and Anderson, D}, title = {A cross-cultural comparison of health-related quality of life and its associated factors among older women in Vietnam and Australia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {174}, pmid = {29534763}, issn = {1756-0500}, mesh = {Aged ; Australia/ethnology ; Chronic Disease/*ethnology ; *Cross-Cultural Comparison ; Female ; Humans ; Life Style/*ethnology ; Middle Aged ; Quality of Life/*psychology ; Vietnam/ethnology ; }, abstract = {OBJECTIVE: This study compared health-related quality of life and its associated factors among 305 women in Vietnam and 175 women in Australia aged 60-71. Descriptive analyses, Chi square, independent t-tests, and General Linear Models were used for data analysis.

RESULTS: After controlling for socio-demographics, lifestyles, and chronic diseases, older women in Vietnam had lower levels of physical health but similar levels of mental health to those in Australia. In both populations, chronic disease and diet were associated with physical health; physical activity was related to mental health. In Australia, physical activity, exercise, and Body Mass Index were also associated with physical health; age, alcohol consumption, and sleep were also linked with mental health. In Vietnam, age and marital status were also related to physical health; chronic diseases and diet were also correlated with mental health. These findings suggested that interventions developed in Australia targeting the management of diet and physical activity, may be useful for older women in Vietnam. However, future interventions in Vietnam need to be tailored to account for different age groups, marital status, and the number of chronic diseases experienced. Further investigation into the contributions of cultural factors to health-related quality of life is recommended.}, } @article {pmid29534756, year = {2018}, author = {Semachew, A}, title = {Implementation of nursing process in clinical settings: the case of three governmental hospitals in Ethiopia, 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {173}, pmid = {29534756}, issn = {1756-0500}, mesh = {Adult ; Documentation/standards/*statistics & numerical data ; Ethiopia ; Female ; Hospitals, Public/standards/*statistics & numerical data ; Humans ; Male ; Nursing/standards/*statistics & numerical data ; Nursing Diagnosis/standards/*statistics & numerical data ; Retrospective Studies ; }, abstract = {OBJECTIVE: The purpose of this survey was to evaluate the implementation of the nursing process at three randomly selected governmental hospitals found in Amhara Region North West Ethiopia.

RESULT: From the total 338 reviewed documents, 264 (78.1%) have a nursing process format attached with the patient's profile/file, 107 (31.7%) had no nursing diagnosis, 185 (54.7%) of nurses stated their plan of care based on priority, 173 (51.2%) of nurses did not document their interventions based on plan and 179 (53.0%) of nurses did not evaluate their interventions. The overall implementation of nursing process among Felege Hiwot Referal hospital, Debretabor general hospital and Finoteselam general hospitals were 49.12, 68.18, and 69.42% respectively. Nursing professionals shall improve documentation required in implementing the nursing process. Nursing managers (matron, ward heads) shall supervise the overall implementation of nursing process. Hospital nursing services managers (matrons) shall arrange and facilitate case presentations by the nursing staffs which focus on documentation and updates on nursing process. Hospitals need to establish and support nursing process coordinating staff in their institution.}, } @article {pmid29534743, year = {2018}, author = {Amandito, R and Putradista, R and Jikesya, C and Utaminingsih, D and Rusin, J and Rohsiswatmo, R and Malik, A}, title = {UGT1A1 gene and neonatal hyperbilirubinemia: a preliminary study from Bengkulu, Indonesia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {172}, pmid = {29534743}, issn = {1756-0500}, support = {No. 2601/UN2.R3.1/HKP05.00/2017//Hibah PUPT 2017 research grant from Directorate for Higher Education, Republic of Indonesia/ ; }, mesh = {Bilirubin/*blood ; Glucuronosyltransferase/*genetics ; Humans ; Hyperbilirubinemia, Neonatal/*blood/*genetics ; Indonesia ; Infant, Newborn ; Polymorphism, Restriction Fragment Length ; }, abstract = {OBJECTIVE: The genetic involvement in unconjugated neonatal hyperbilirubinemia has been extensively studied. Despite the high incidence of hyperbilirubinemia in Indonesia, studies are lacking. The objective of this study is to elucidate the role of polymorphism in the UGT1A1 in Neonatal Hyperbilirubinemia in Bengkulu, Indonesia.

RESULTS: There were 41 neonates enrolled in the study; 30 had a total serum bilirubin level ≥ 15 mg/dL (hyperbilirubinemia neonates) while 11 has < 15 mg/dL (control neonates). Genetic mutations in Exon 1, UGT1A1*6 (c211g > a) and one in promoter region, UGT1A1*60 (c3279t > g) were determined by polymerase chain reaction-restriction fragment length polymorphism. We found 18 (60%) mutation in exon 1 in hyperbilirubinemia group and 7 (64%) in the control group with an identical allele frequency of 0.3 in both groups. We found heterozygous UGT1A1*60 4 times (13.3%) and homozygous 26 times (86.7%) in the hyperbilirubinemia group, with an identical allele frequency of 0.935 in hyperbilirubinemia and 1 in control group. This study supports the involvement of genetic factors in the development of unconjugated hyperbilirubinemia in Bengkulu population.}, } @article {pmid29534719, year = {2018}, author = {Méheust, R and Bhattacharya, D and Pathmanathan, JS and McInerney, JO and Lopez, P and Bapteste, E}, title = {Formation of chimeric genes with essential functions at the origin of eukaryotes.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {30}, pmid = {29534719}, issn = {1741-7007}, abstract = {BACKGROUND: Eukaryotes evolved from the symbiotic association of at least two prokaryotic partners, and a good deal is known about the timings, mechanisms, and dynamics of these evolutionary steps. Recently, it was shown that a new class of nuclear genes, symbiogenetic genes (S-genes), was formed concomitant with endosymbiosis and the subsequent evolution of eukaryotic photosynthetic lineages. Understanding their origins and contributions to eukaryogenesis would provide insights into the ways in which cellular complexity has evolved.

RESULTS: Here, we show that chimeric nuclear genes (S-genes), built from prokaryotic domains, are critical for explaining the leap forward in cellular complexity achieved during eukaryogenesis. A total of 282 S-gene families contributed solutions to many of the challenges faced by early eukaryotes, including enhancing the informational machinery, processing spliceosomal introns, tackling genotoxicity within the cell, and ensuring functional protein interactions in a larger, more compartmentalized cell. For hundreds of S-genes, we confirmed the origins of their components (bacterial, archaeal, or generally prokaryotic) by maximum likelihood phylogenies. Remarkably, Bacteria contributed nine-fold more S-genes than Archaea, including a two-fold greater contribution to informational functions. Therefore, there is an additional, large bacterial contribution to the evolution of eukaryotes, implying that fundamental eukaryotic properties do not strictly follow the traditional informational/operational divide for archaeal/bacterial contributions to eukaryogenesis.

CONCLUSION: This study demonstrates the extent and process through which prokaryotic fragments from bacterial and archaeal genes inherited during eukaryogenesis underly the creation of novel chimeric genes with important functions.}, } @article {pmid29534701, year = {2018}, author = {Bockmeyer, CL and Wittig, J and Säuberlich, K and Selhausen, P and Eßer, M and Zeuschner, P and Modde, F and Amann, K and Daniel, C}, title = {Recommendations for mRNA analysis of micro-dissected glomerular tufts from paraffin-embedded human kidney biopsy samples.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {2}, pmid = {29534701}, issn = {1471-2199}, support = {15-06-14-1-Bockmeyer//IZKF and ELAN from University Hospital Erlangen-Nuremberg/International ; 07-2012//Dr. Werner Jackstädt-Stiftung/International ; }, mesh = {Adult ; Biopsy ; Female ; Gene Expression Profiling/*standards ; Humans ; Kidney/chemistry/*pathology ; Laser Capture Microdissection/*methods ; Male ; Middle Aged ; Organ Specificity ; Paraffin Embedding ; RNA, Messenger/*analysis ; Young Adult ; }, abstract = {BACKGROUND: Glomeruli are excellent pre-determined natural structures for laser micro-dissection. Compartment-specific glomerular gene expression analysis of formalin-fixed paraffin-embedded renal biopsies could improve research applications. The major challenge for such studies is to obtain good-quality RNA from small amounts of starting material, as applicable for the analysis of glomerular compartments. In this work, we provide data and recommendations for an optimized workflow of glomerular mRNA analysis.

RESULTS: With a proper resolution of the camera and screen provided by the next generation of micro-dissection systems, we are able to separate parietal epithelial cells from glomerular tufts. Selected compartment-specific transcripts (WT1 and GLEPP1 for glomerular tuft as well as PAX2 for parietal epithelial cells) seem to be reliable discriminators for these micro-dissected glomerular substructures. Using the phenol-chloroform extraction and hemalaun-stained sections (2 µm), high amounts of Bowman's capsule transections (> 300) reveal sufficient RNA concentrations (> 300 ng mRNA) for further analysis. For comparison, in unstained sections from a number of 60 glomerular transections upwards, a minimum amount of 157 ng mRNA with a reasonable mRNA purity [A260/A280 ratio of 1.5 (1.4/1.7) median (25th/75th percentiles)] was reversely transcribed into cDNA. Comparing the effect of input RNA (20, 60, 150 and 300 micro-dissected glomerular transections), transcript expression of POLR2A significantly correlated when 60 and 150 laser micro-dissected glomerular transections were used for analysis. There was a lower inter-assay coefficient of variability for ADAMTS13, when at least 60 glomerular transections were used. According to the algorithms of geNormPlus and NormFinder, PGK1 and PPIA are more stable glomerular reference transcripts compared to GUSB, GAPDH, POLR2A, RPLPO, TBP, B2M, ACTB, 18SrRNA and HMBS.

CONCLUSIONS: Our approach implements compartment-specific glomerular mRNA expression analysis into research applications, even regarding glomerular substructures like parietal epithelial cells. We recommend using of at least 60 micro-dissected unstained glomerular or 300 hemalaun-stained Bowman's capsule transections to obtain sufficient input mRNA for reproducible results. Hereby, the range of RNA concentrations in 60 micro-dissected glomeruli is low and appropriate normalization of Cq values using our suggested reference transcripts (PGK1 and PPIA) allows compensation with respect to different amounts of RNA purity and quantity.}, } @article {pmid29534677, year = {2018}, author = {Kluge, M and Friedel, CC}, title = {Watchdog - a workflow management system for the distributed analysis of large-scale experimental data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {97}, pmid = {29534677}, issn = {1471-2105}, support = {FR2938/7-1//Deutsche Forschungsgemeinschaft/International ; CRC 1123 (Z2)//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Computational Biology/*methods ; Herpes Simplex/genetics/virology ; Herpesvirus 1, Human/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; RNA/*analysis/genetics ; *Software ; User-Computer Interface ; *Virus Replication ; *Workflow ; }, abstract = {BACKGROUND: The development of high-throughput experimental technologies, such as next-generation sequencing, have led to new challenges for handling, analyzing and integrating the resulting large and diverse datasets. Bioinformatical analysis of these data commonly requires a number of mutually dependent steps applied to numerous samples for multiple conditions and replicates. To support these analyses, a number of workflow management systems (WMSs) have been developed to allow automated execution of corresponding analysis workflows. Major advantages of WMSs are the easy reproducibility of results as well as the reusability of workflows or their components.

RESULTS: In this article, we present Watchdog, a WMS for the automated analysis of large-scale experimental data. Main features include straightforward processing of replicate data, support for distributed computer systems, customizable error detection and manual intervention into workflow execution. Watchdog is implemented in Java and thus platform-independent and allows easy sharing of workflows and corresponding program modules. It provides a graphical user interface (GUI) for workflow construction using pre-defined modules as well as a helper script for creating new module definitions. Execution of workflows is possible using either the GUI or a command-line interface and a web-interface is provided for monitoring the execution status and intervening in case of errors. To illustrate its potentials on a real-life example, a comprehensive workflow and modules for the analysis of RNA-seq experiments were implemented and are provided with the software in addition to simple test examples.

CONCLUSIONS: Watchdog is a powerful and flexible WMS for the analysis of large-scale high-throughput experiments. We believe it will greatly benefit both users with and without programming skills who want to develop and apply bioinformatical workflows with reasonable overhead. The software, example workflows and a comprehensive documentation are freely available at www.bio.ifi.lmu.de/watchdog.}, } @article {pmid29534675, year = {2018}, author = {Zhang, P and Huang, K and Zhang, B and Dunn, DW and Chen, D and Li, F and Qi, X and Guo, S and Li, B}, title = {High polymorphism in MHC-DRB genes in golden snub-nosed monkeys reveals balancing selection in small, isolated populations.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {29}, pmid = {29534675}, issn = {1471-2148}, support = {2016YFC0503202//the National Key Programme of Research and Development, the Ministry of Science and Technology of China/International ; 31501872//the National Natural Science Foundation of China/International ; 31730104//the National Natural Science Foundation of China/International ; 31770425//the National Natural Science Foundation of China/International ; 31770411//the National Natural Science Foundation of China/International ; }, mesh = {Alleles ; Animals ; Base Sequence ; China ; Colobinae/*genetics ; Exons/genetics ; Gene Frequency/genetics ; *Genetics, Population ; Geography ; HLA-DR beta-Chains/*genetics ; Likelihood Functions ; Major Histocompatibility Complex/*genetics ; Microsatellite Repeats/genetics ; Phylogeny ; *Polymorphism, Genetic ; *Selection, Genetic ; Species Specificity ; }, abstract = {BACKGROUND: Maintaining variation in immune genes, such as those of the major histocompatibility complex (MHC), is important for individuals in small, isolated populations to resist pathogens and parasites. The golden snub-nosed monkey (Rhinopithecus roxellana), an endangered primate endemic to China, has experienced a rapid reduction in numbers and severe population fragmentation over recent years. For this study, we measured the DRB diversity among 122 monkeys from three populations in the Qinling Mountains, and estimated the relative importance of different agents of selection in maintaining variation of DRB genes.

RESULTS: We identified a total of 19 DRB sequences, in which five alleles were novel. We found high DRB variation in R. roxellana and three branches of evidence suggesting that balancing selection has contributed to maintaining MHC polymorphism over the long term in this species: i) different patterns of both genetic diversity and population differentiation were detected at MHC and neutral markers; ii) an excess of non-synonymous substitutions compared to synonymous substitutions at antigen binding sites, and maximum-likelihood-based random-site models, showed significant positive selection; and iii) phylogenetic analyses revealed a pattern of trans-species evolution for DRB genes.

CONCLUSIONS: High levels of DRB diversity in these R. roxellana populations may reflect strong selection pressure in this species. Patterns of genetic diversity and population differentiation, positive selection, as well as trans-species evolution, suggest that pathogen-mediated balancing selection has contributed to maintaining MHC polymorphism in R. roxellana over the long term. This study furthers our understanding of the role pathogen-mediated balancing selection has in maintaining variation in MHC genes in small and fragmented populations of free-ranging vertebrates.}, } @article {pmid29534596, year = {2018}, author = {Arnocky, S}, title = {Self-Perceived Mate Value, Facial Attractiveness, and Mate Preferences: Do Desirable Men Want It All?.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704918763271}, doi = {10.1177/1474704918763271}, pmid = {29534596}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; *Beauty ; Choice Behavior ; Humans ; Individuality ; Male ; Marriage/*psychology ; Men ; Sexual Behavior/*psychology ; Sexual Partners/*psychology ; Young Adult ; }, abstract = {Ten years ago, Buss and Shackelford demonstrated that high mate value (i.e., physically attractive) women held more discerning mate preferences relative to lower mate value women. Since then, researchers have begun to consider the equally important role of men's sexual selectivity in human mate choice. Yet, little research has focused on whether high mate value men are similarly choosy in their mate preferences. In a sample of 139 undergraduate men, relationships between self-perceived mate value as well as female-rated facial attractiveness were examined in relation to men's expressed mate preferences. Results showed that self-perceived mate value was unrelated to men's facial attractiveness as rated by women. Men who believed they were of high mate value were more likely than lower mate value men to prefer to marry at a younger age; to have a spouse who was younger than them; and to have a partner who was sociable, ambitious, high in social status, with good financial prospects, a desire for children, health, good looks, and mutual attraction. Objective male facial attractiveness was generally unrelated to heightened mate preferences, with the exception of heightened preference for similar religious background and good physical health. Findings suggest that men who perceive themselves as high in overall mate value are selective in their mate choice in a manner similar to high mate value women.}, } @article {pmid29534199, year = {2018}, author = {Petrovich, M and Chu, B and Wright, D and Griffin, J and Elfeki, M and Murphy, BT and Poretsky, R and Wells, G}, title = {Antibiotic resistance genes show enhanced mobilization through suspended growth and biofilm-based wastewater treatment processes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy041}, pmid = {29534199}, issn = {1574-6941}, abstract = {Wastewater treatment plants (WWTPs) are known to harbor antibiotic resistance genes (ARGs) that are disseminated into the environment via effluent. However, few studies have compared abundance, mobilization and selective pressures for ARGs in WWTPs as a function of variations in secondary treatment bioprocesses. We used shotgun metagenomics to provide a comprehensive analysis of ARG composition, relationship to mobile genetic elements and co-occurrences with antibiotic production genes (APGs) throughout two full-scale municipal WWTPs, one of which employs biofilm-based secondary treatment and another that uses a suspended growth system. Results showed that abundances of ARGs declined by over 90% per genome equivalent in both types of wastewater treatment processes. However, the fractions of ARGs associated with mobile genetic elements increased substantially between influent and effluent in each plant, indicating significant mobilization of ARGs throughout both treatment processes. Strong positive correlations between ARGs and APGs were found for the aminoglycoside antibiotic class in the suspended growth system and for the streptogramin antibiotic class in the biofilm system. The biofilm and suspended growth WWTPs exhibited similarities in ARG abundances, composition and mobilization trends. However, clear differences were observed for within-plant ARG persistence. These findings suggest that both biofilm and suspended growth-based WWTPs may promote genetic mobilization of persistent ARGs that are then disseminated in effluent to receiving water bodies.}, } @article {pmid29533941, year = {2018}, author = {Falk, D and Zollikofer, CPE and Ponce de León, M and Semendeferi, K and Alatorre Warren, JL and Hopkins, WD}, title = {Identification of in vivo Sulci on the External Surface of Eight Adult Chimpanzee Brains: Implications for Interpreting Early Hominin Endocasts.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {1}, pages = {45-58}, doi = {10.1159/000487248}, pmid = {29533941}, issn = {1421-9743}, abstract = {The only direct source of information about hominin brain evolution comes from the fossil record of endocranial casts (endocasts) that reproduce details of the external morphology of the brain imprinted on the walls of the braincase during life. Surface traces of sulci that separate the brain's convolutions (gyri) are reproduced sporadically on early hominin endocasts. Paleoneurologists rely heavily on published descriptions of sulci on brains of great apes, especially chimpanzees (humans' phylogenetically closest living relatives), to guide their identifications of sulci on ape-sized hominin endocasts. However, the few comprehensive descriptions of cortical sulci published for chimpanzees usually relied on post mortem brains, (now) antiquated terminology for some sulci, and photographs or line drawings from limited perspectives (typically right or left lateral views). The shortage of adequate descriptions of chimpanzee sulcal patterns partly explains why the identities of certain sulci on australopithecine endocasts (e.g., the inferior frontal and middle frontal sulci) have been controversial. Here, we provide images of lateral and dorsal surfaces of 16 hemispheres from 4 male and 4 female adult chimpanzee brains that were obtained using in vivo magnetic resonance imaging. Sulci on the exposed surfaces of the frontal, parietal, temporal, and occipital lobes are identified on the images based on their locations, positions relative to each other, and homologies known from comparative studies of cytoarchitecture in primates. These images and sulcal identifications exceed the quantity and quality of previously published illustrations of chimpanzee brains with comprehensively labeled sulci and, thus, provide a larger number of examples for identifying sulci on hominin endocasts than hitherto available. Our findings, even in a small sample like the present one, overturn published claims that australopithecine endocasts reproduce derived configurations of certain sulci in their frontal lobes that never appear on chimpanzee brains. The sulcal patterns in these new images also suggest that changes in two gyri that bridge between the parietal and occipital lobes may have contributed to cortical reorganization in early hominins. It is our hope that these labeled in vivo chimpanzee brains will assist future researchers in identifying sulci on hominin endocasts, which is a necessary first step in the quest to learn how and when the external morphology of the human cerebral cortex evolved from apelike precursors.}, } @article {pmid29533845, year = {2018}, author = {Hudson, GA and Mitchell, DA}, title = {RiPP antibiotics: biosynthesis and engineering potential.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {61-69}, pmid = {29533845}, issn = {1879-0364}, support = {R01 GM097142/GM/NIGMS NIH HHS/United States ; }, abstract = {The threat of antibiotic resistant bacterial infections continues to underscore the need for new treatment options. Historically, small molecule metabolites from microbes have provided a rich source of antibiotic compounds, and as a result, significant effort has been invested in engineering the responsible biosynthetic pathways to generate novel analogs with attractive pharmacological properties. Unfortunately, biosynthetic stringency has limited the capacity of non-ribosomal peptide synthetases and polyketide synthases from producing substantially different analogs in large numbers. Another class of natural products, the ribosomally synthesized and post-translationally modified peptides (RiPPs), have rapidly expanded in recent years with many natively displaying potent antibiotic activity. RiPP biosynthetic pathways are modular and intrinsically tolerant to alternative substrates. Several prominent RiPPs with antibiotic activity will be covered in this review with a focus on their biosynthetic plasticity. While only a few RiPP enzymes have been thoroughly investigated mechanistically, this knowledge has already been harnessed to generate new-to-nature compounds. Through the use of synthetic biology approaches, on-going efforts in RiPP engineering hold great promise in unlocking the potential of this natural product class.}, } @article {pmid29533177, year = {2018}, author = {Jamjan, W and Suriyachadkun, C and Tanasupawat, S and Sakai, K and Tashiro, Y and Okugawa, Y and Tongpim, S}, title = {Amycolatopsis silviterrae sp. nov., isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1455-1460}, doi = {10.1099/ijsem.0.002687}, pmid = {29533177}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; *Forests ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinobacterial strain, designated C12CA1T, was isolated from forest soil in the conservation area of Chulabhorn dam, Thailand, and its taxonomic position was determined by using a polyphasic approach. Strain C12CA1T contained meso-2,6 diaminopimelic acid in the cell-wall peptidoglycan, and arabinose and galactose as diagnostic sugars of the whole-cell hydrolysate. On the basis of morphological and chemotaxonomic characteristics, strain C12CA1T was classified in the genus Amycolatopsis. It contained MK-9(H4) as the predominant menaquinone, C16 : 0, iso-C15 : 0 and iso-C16 : 0 as the major cellular fatty acids, and several phospholipids consisting of diphosphotidylglycerol, phosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylserine, phosphatidylinositol, hydroxyphosphatidylethanolamine, phosphatidylinositol mannosides and an unidentified glucosamine-containing phospholipid. Based on 16S rRNA gene sequence and phylogenetic analyses, strain C12CA1T was closely related to Amycolatopsis vancoresmycina DSM 44592T (98.96 %) and Amycolatopsis pretoriensis JCM 12673T (98.82 %). The strain exhibited low DNA-DNA relatedness values with A. vancoresmycina DSM 44592T (6.9±0.2-11.6±1.9 %) and A. pretoriensis JCM 12673T (8.8±0.3-9.2±1.8 %). The DNA G+C content of strain C12CA1T was 69.8 mol%. Based on the results of polyphasic characterization, strain C12CA1T represents a novel species of the genus Amycolatopsis, for which the name Amycolatopsis silviterrae sp. nov. is proposed. The type strain is C12CA1T (=TBRC 1456T=NBRC 111116T).}, } @article {pmid29533175, year = {2018}, author = {Morales-Covarrubias, MS and Del Carmen Bolan-Mejía, M and Vela Alonso, AI and Fernandez-Garayzabal, JF and Gomez-Gil, B}, title = {Streptococcus penaeicida sp. nov., isolated from a diseased farmed Pacific white shrimp (Penaeus vannamei).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1490-1495}, doi = {10.1099/ijsem.0.002693}, pmid = {29533175}, issn = {1466-5034}, mesh = {Animals ; Aquaculture ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Guatemala ; Penaeidae/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptococcus/*classification/genetics/isolation & purification ; }, abstract = {Strain CAIM 1838T, isolated from the hepatopancreas of a cultured diseased Pacific white shrimp (Penaeus vannamei), was subjected to characterization by a polyphasic taxonomic approach. On the basis of 16S rRNA gene sequence analysis, strain CAIM 1838T was most closely related to Streptococcus bovimastitidis 99.3 % and to other species of the Pyogenes clade of Streptococcus with lower similarity values. Average nucleotide identity values and the genome-to-genome distance of strain CAIM 1838T, as compared with the type strains, confirmed the separate species status with closely related species of the genus Streptococcus and were all below the thresholds to delimit a species, 93.1 and 49.4 %, respectively. The DNA G+C content was 38.1 mol%. Differential phylogenetic distinctiveness together with phenotypic properties obtained in this study revealed that strain CAIM 1838T could be differentiated from the closely related species. Based on these results it is proposed that strain CAIM 1838T represents a novel species in the genus Streptococcus, for which the name Streptococcus penaeicida sp. nov is proposed (type strain, CAIM 1838T=CECT 8596T,=DSM26545T), is proposed.}, } @article {pmid29533174, year = {2018}, author = {Liu, X and Lai, Q and Du, Y and Zhang, X and Liu, Z and Sun, F and Shao, Z}, title = {Neptunicella marina gen. nov., sp. nov., isolated from surface seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1423-1428}, doi = {10.1099/ijsem.0.002660}, pmid = {29533174}, issn = {1466-5034}, mesh = {Alteromonadaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Indian Ocean ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Water Microbiology ; }, abstract = {A Gram-stain-negative, aerobic, short rod-shaped bacterium with a single polar flagellum, designated strain S27-2T, was isolated from surface seawater from the Indian Ocean. Growth was observed in 0-12.0 % (w/v) NaCl with an optimum of 0.5-2.0 % (w/v) NaCl, pH 6.0-9.0 with an optimum of pH 7.0, and growth temperature of 10-41 °C with an optimum of 25-37 °C. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain S27-2T belonged to the family Alteromonadaceae and formed a distinct lineage with the type strain of Pseudobowmanella zhangzhouensis. Levels of 16S rRNA gene sequence similarity between strain S27-2T and members of related genera included in the trees ranged from 86.7 to 93.8 %. Strain S27-2T contained Q-8 as the predominant ubiquinone. The principal fatty acids (>10 %) were C16 : 0 (22.1 %), C16 : 1ω7c/ω6c (22.7 %) and C18 : 1ω7c/ω6c (20.1 %). The polar lipids consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, one unidentified phospholipid and two unknown lipids. The G+C content of strain S27-2T was 43.7 mol%. On the basis of the polyphasic taxonomic evidence presented in this study, strain S27-2T should be classified as a novel species in a new genus within the family Alteromonadaceae, for which the name Neptunicella marina gen. nov., sp. nov. is proposed, with the type strain S27-2T (= KCTC52335T=MCCC 1A02149T).}, } @article {pmid29533171, year = {2018}, author = {Ranchou-Peyruse, M and Goñi-Urriza, M and Guignard, M and Goas, M and Ranchou-Peyruse, A and Guyoneaud, R}, title = {Pseudodesulfovibrio hydrargyri sp. nov., a mercury-methylating bacterium isolated from a brackish sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1461-1466}, doi = {10.1099/ijsem.0.002173}, pmid = {29533171}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Deltaproteobacteria/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; France ; Geologic Sediments/*microbiology ; Mercury/*chemistry ; Oxidation-Reduction ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfur-Reducing Bacteria/classification/genetics/isolation & purification ; *Water Microbiology ; }, abstract = {The strain BerOc1T was isolated from brackish sediments contaminated with hydrocarbons and heavy metals. This strain has been used as a model strain of sulfate-reducer to study the biomethylation of mercury. The cells are vibrio-shaped, motile and not sporulated. Phylogeny and physiological traits placed this strain within the genus Pseudodesulfovibrio. Optimal growth was obtained at 30 °C, 1.5 % NaCl and pH 6.0-7.4. The estimated G+C content of the genomic DNA was 62.6 mol%. BerOc1T used lactate, pyruvate, fumarate, ethanol and hydrogen. Terminal electron acceptors used were sulfate, sulfite, thiosulfate and DMSO. Only pyruvate could be used without a terminal electron acceptor. The major fatty acids were C18 : 0, anteiso-C15 : 0, C16 : 0 and C18 : 1ω7. The name Pseudodesulfovibrio hydrargyri sp. nov. is proposed for the type strain BerOc1T (DSM 10384T=JCM 31820T).}, } @article {pmid29533170, year = {2018}, author = {Tseng, M and Chiang, WP and Liao, HC and Hsieh, SY and Yuan, GF}, title = {Saccharomonospora piscinae sp. nov., a novel actinobacterium from fishpond sediment in Taiwan.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1418-1422}, doi = {10.1099/ijsem.0.002653}, pmid = {29533170}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Aquaculture ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; *Phylogeny ; Ponds/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Taiwan ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain 06168H-1T was isolated from a fishpond sediment sample collected from the southern area of Taiwan, and a polyphasic approach was used to determine its taxonomic position. The isolate grew between 20-40 °C and 0-8 % (w/v) NaCl. It produced branched and unfragmented substrate mycelia. Short spore chains (3-10 spores per chain) formed on branched aerial mycelia. The spore chains contained non-motile, smooth-surfaced, oval spores. Galactose, arabinose and ribose were the whole-cell sugars and meso-diaminopimelic acid was present in its peptidoglycan. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylcholine, hydroxyphosphati dylethanolamine and a ninhydrin-positive phosphoglycolipid. The predominant menaquinone was MK-9(H4) and minor components were MK-8(H4) and MK-9(H6). Mycolic acids were not detected. The major cellular fatty acids were iso-C16 : 0 and C17 : 1ω6c and C17 : 0ω8c. The DNA G+C content of the strain was 70.6 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed this strain clustered with the members of the genus Saccharomonospora and was closely related to Saccharomonospora xinjiangensis, Saccharomonospora azurea and Saccharomonosporacyanea. The levels of similarity between this strain and the closely related species were: Sxinjiangensis BCRC16887T, 98.34 %; S. azurea BCRC 16220T, 98.27 %; and S. cyanea BCRC 16886T, 97.99 %. Based on phylogenetic characteristics, strain 06168H-1T represents a novel species of the genus Saccharomonospora. We thus propose the name Saccharomonospora piscinae sp. nov. for this novel strain, with strain 06168H-1T (=BCRC 16893T=KCTC 19743T) as the type strain.}, } @article {pmid29533010, year = {2018}, author = {Maldonado-Chaparro, AA and Montiglio, PO and Forstmeier, W and Kempenaers, B and Farine, DR}, title = {Linking the fine-scale social environment to mating decisions: a future direction for the study of extra-pair paternity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1558-1577}, doi = {10.1111/brv.12408}, pmid = {29533010}, issn = {1469-185X}, abstract = {Variation in extra-pair paternity (EPP) among individuals of the same population could result from stochastic demography or from individual differences in mating strategies. Although the adaptive value of EPP has been widely studied, much less is known about the characteristics of the social environment that drive the observed patterns of EPP. Here, we demonstrate how concepts and well-developed tools for the study of social behaviour (such as social network analysis) can enhance the study of extra-pair mating decisions (focussing in particular on avian mating systems). We present several hypotheses that describe how characteristics of the social environment in which individuals are embedded might influence the levels of EPP in a socially monogamous population. We use a multi-level social approach (Hinde, 1976) to achieve a detailed description of the social structure and social dynamics of individuals in a group. We propose that the pair-bond, the direct (local) social environment and the indirect (extended) social environment, can contribute in different ways to the variation observed in the patterns of EPP, at both the individual and the population level. A strength of this approach is that it integrates into the analysis (indirect) interactions with all potential mates in a population, thus extending the current framework to study extra-pair mating behaviour. We also encourage the application of social network methods such as temporal dynamic analysis to depict temporal changes in the patterns of interactions among individuals in a group, and to study how this affects mating behaviour. We argue that this new framework will contribute to a better understanding of the proximate mechanisms that drive variation in EPP within populations in socially monogamous species, and might ultimately provide insights into the evolution and maintenance of mating systems.}, } @article {pmid29532568, year = {2018}, author = {Paccard, A and Wasserman, BA and Hanson, D and Astorg, L and Durston, D and Kurland, S and Apgar, TM and El-Sabaawi, RW and Palkovacs, EP and Hendry, AP and Barrett, RDH}, title = {Adaptation in temporally variable environments: stickleback armor in periodically breaching bar-built estuaries.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {735-752}, doi = {10.1111/jeb.13264}, pmid = {29532568}, issn = {1420-9101}, abstract = {The evolutionary consequences of temporal variation in selection remain hotly debated. We explored these consequences by studying threespine stickleback in a set of bar-built estuaries along the central California coast. In most years, heavy rains induce water flow strong enough to break through isolating sand bars, connecting streams to the ocean. New sand bars typically re-form within a few weeks or months, thereby re-isolating populations within the estuaries. These breaching events cause severe and often extremely rapid changes in abiotic and biotic conditions, including shifts in predator abundance. We investigated whether this strong temporal environmental variation can maintain within-population variation while eroding adaptive divergence among populations that would be caused by spatial variation in selection. We used neutral genetic markers to explore population structure and then analysed how stickleback armor traits, the associated genes Eda and Pitx1 and elemental composition (%P) varies within and among populations. Despite strong gene flow, we detected evidence for divergence in stickleback defensive traits and Eda genotypes associated with predation regime. However, this among-population variation was lower than that observed among other stickleback populations exposed to divergent predator regimes. In addition, within-population variation was very high as compared to populations from environmentally stable locations. Elemental composition was strongly associated with armor traits, Eda genotype and the presence of predators, thus suggesting that spatiotemporal variation in armor traits generates corresponding variation in elemental phenotypes. We conclude that gene flow, and especially temporal environmental variation, can maintain high levels of within-population variation while reducing, but not eliminating, among-population variation driven by spatial environmental variation.}, } @article {pmid29532150, year = {2018}, author = {Kisková, J and Perháčová, Z and Vlčko, L and Sedláková, J and Kvasnová, S and Pristaš, P}, title = {The Bacterial Population of Neutral Mine Drainage Water of Elizabeth's Shaft (Slovinky, Slovakia).}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {988-996}, pmid = {29532150}, issn = {1432-0991}, support = {VEGA 1/0229/17//Ministry of Education, Science, Research and Sport of Slovak Republic/ ; VVGS-2016-275//Pavol Jozef Šafárik University in Košice/ ; No. 734684//H2020-MSCA-RISE-2016-CHARMED/ ; }, mesh = {Actinobacteria/classification/genetics/*isolation & purification ; Chloroflexi/classification/genetics/*isolation & purification ; DNA, Bacterial/genetics ; Iron/*analysis ; Mining ; Nucleic Acid Amplification Techniques ; Proteobacteria/classification/genetics/*isolation & purification ; RNA, Ribosomal, 16S/genetics ; Slovakia ; Sulfur/*analysis ; Waste Water/*chemistry/*microbiology ; Water Quality ; }, abstract = {Although neutral mine drainage is the less frequent subject of the interest than acid mine drainage, it can have adverse environmental effects caused mainly by precipitation of dissolved Fe. The aim of the study was to characterize the composition of bacterial population in environment with high concentration of iron and sulfur compounds represented by neutral mine drainage water of Elizabeth's shaft, Slovinky (Slovakia). Direct microscopic observations, cultivation methods, and 454 pyrosequencing of the 16S rRNA gene amplicons were used to examine the bacterial population. Microscopic observations identified iron-oxidizing Proteobacteria of the genera Gallionella and Leptothrix which occurrence was not changed during the years 2008-2014. Using 454 pyrosequencing, there were identified members of 204 bacterial genera that belonged to 25 phyla. Proteobacteria (69.55%), followed by Chloroflexi (10.31%) and Actinobacteria (4.24%) dominated the bacterial community. Genera Azotobacter (24.52%) and Pseudomonas (14.15%), followed by iron-oxidizing Proteobacteria Dechloromonas (11%) and Methyloversatilis (8.53%) were most abundant within bacterial community. Typical sulfur bacteria were detected with lower frequency, e.g., Desulfobacteraceae (0.25%), Desulfovibrionaceae (0.16%), or Desulfobulbaceae (0.11%). Our data indicate that the composition of bacterial community of the Elizabeth's shaft drainage water reflects observed neutral pH, high level of iron and sulfur ions in this aquatic habitat.}, } @article {pmid29531716, year = {2018}, author = {Preite, V and Oplaat, C and Biere, A and Kirschner, J and van der Putten, WH and Verhoeven, KJF}, title = {Increased transgenerational epigenetic variation, but not predictable epigenetic variants, after environmental exposure in two apomictic dandelion lineages.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {3047-3059}, pmid = {29531716}, issn = {2045-7758}, abstract = {DNA methylation is one of the mechanisms underlying epigenetic modifications. DNA methylations can be environmentally induced and such induced modifications can at times be transmitted to successive generations. However, it remains speculative how common such environmentally induced transgenerational DNA methylation changes are and if they persist for more than one offspring generation. We exposed multiple accessions of two different apomictic dandelion lineages of the Taraxacum officinale group (Taraxacum alatum and T. hemicyclum) to drought and salicylic acid (SA) treatment. Using methylation-sensitive amplified fragment length polymorphism markers (MS-AFLPs) we screened anonymous methylation changes at CCGG restriction sites throughout the genome after stress treatments and assessed the heritability of induced changes for two subsequent unexposed offspring generations. Irrespective of the initial stress treatment, a clear buildup of heritable DNA methylation variation was observed across three generations, indicating a considerable background rate of heritable epimutations. Less evidence was detected for environmental effects. Drought stress showed some evidence for accession-specific methylation changes, but only in the exposed generation and not in their offspring. By contrast, SA treatment caused an increased rate of methylation change in offspring of treated plants. These changes were seemingly undirected resulting in increased transgenerational epigenetic variation between offspring individuals, but not in predictable epigenetic variants. While the functional consequences of these MS-AFLP-detected DNA methylation changes remain to be demonstrated, our study shows that (1) stress-induced transgenerational DNA methylation modification in dandelions is genotype and context-specific; and (2) inherited environmental DNA methylation effects are mostly undirected and not targeted to specific loci.}, } @article {pmid29531715, year = {2018}, author = {Hwang, J and Kim, Y and Lee, SW and Kim, NY and Chun, MS and Lee, H and Gottdenker, N}, title = {Anthropogenic food provisioning and immune phenotype: Association among supplemental food, body condition, and immunological parameters in urban environments.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {3037-3046}, pmid = {29531715}, issn = {2045-7758}, abstract = {Direct or indirect supplemental feeding of free-ranging animals occurs worldwide, resulting in significant impacts on population density or altered demographic processes. Another potential impact of increased energy intake from supplemental feeding is altered immunocompetence. As immune system maintenance is energetically costly, there may be trade-offs between immune responses and other energy-demanding physiological processes in individual animals. Although increased availability of food sources through supplemental feeding is expected to increase the overall immunocompetence of animals, empirical data verifying the association between supplemental feeding and different immune parameters are lacking. Understanding the potential influence of supplemental feeding on immune phenotypes is critical, as it may also impact host-pathogen dynamics in free-ranging animals. Using urban stray cats as a study model, we tested for associations between the intensity of supplemental feeding due to cat caretaker activity (CCA); body condition; and immune phenotype (bacterial killing assay (BKA), immunoglobulin G (IgG) concentration, and leukocyte counts). Significantly higher bacterial killing ability was observed in cats from high CCA districts, whereas higher IgG concentration and eosinophil counts were observed in cats from low CCA districts. Other leukocyte counts and body condition indices showed no significant association with CCA. We observed varying patterns of different immune components in relation to supplemental feeding. Out data suggest that supplemental feeding influences immune phenotype, not only by means of energy provisioning, but also by potentially reducing exposure rates to parasite infections through stray cat behavioral changes.}, } @article {pmid29531714, year = {2018}, author = {Bennett, KL and Kaddumukasa, M and Shija, F and Djouaka, R and Misinzo, G and Lutwama, J and Linton, YM and Walton, C}, title = {Comparative phylogeography of Aedes mosquitoes and the role of past climatic change for evolution within Africa.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {3019-3036}, pmid = {29531714}, issn = {2045-7758}, abstract = {The study of demographic processes involved in species diversification and evolution ultimately provides explanations for the complex distribution of biodiversity on earth, indicates regions important for the maintenance and generation of biodiversity, and identifies biological units important for conservation or medical consequence. African and forest biota have both received relatively little attention with regard to understanding their diversification, although one possible mechanism is that this has been driven by historical climate change. To investigate this, we implemented a standard population genetics approach along with Approximate Bayesian Computation, using sequence data from two exon-primed intron-crossing (EPIC) nuclear loci and mitochondrial cytochrome oxidase subunit I, to investigate the evolutionary history of five medically important and inherently forest dependent mosquito species of the genus Aedes. By testing different demographic hypotheses, we show that Aedes bromeliae and Aedes lilii fit the same model of lineage diversification, admixture, expansion, and recent population structure previously inferred for Aedes aegypti. In addition, analyses of population structure show that Aedes africanus has undergone lineage diversification and expansion while Aedes hansfordi has been impacted by population expansion within Uganda. This congruence in evolutionary history is likely to relate to historical climate-driven habitat change within Africa during the late Pleistocene and Holocene epoch. We find differences in the population structure of mosquitoes from Tanzania and Uganda compared to Benin and Uganda which could relate to differences in the historical connectivity of forests across the continent. Our findings emphasize the importance of recent climate change in the evolution of African forest biota.}, } @article {pmid29531713, year = {2018}, author = {Elías-Gutiérrez, M and Valdez-Moreno, M and Topan, J and Young, MR and Cohuo-Colli, JA}, title = {Improved protocols to accelerate the assembly of DNA barcode reference libraries for freshwater zooplankton.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {3002-3018}, pmid = {29531713}, issn = {2045-7758}, abstract = {Currently, freshwater zooplankton sampling and identification methodologies have remained virtually unchanged since they were first established in the beginning of the XX century. One major contributing factor to this slow progress is the limited success of modern genetic methodologies, such as DNA barcoding, in several of the main groups. This study demonstrates improved protocols which enable the rapid assessment of most animal taxa inhabiting any freshwater system by combining the use of light traps, careful fixation at low temperatures using ethanol, and zooplankton-specific primers. We DNA-barcoded 2,136 specimens from a diverse array of taxonomic assemblages (rotifers, mollusks, mites, crustaceans, insects, and fishes) from several Canadian and Mexican lakes with an average sequence success rate of 85.3%. In total, 325 Barcode Index Numbers (BINs) were detected with only three BINs (two cladocerans and one copepod) shared between Canada and Mexico, suggesting a much narrower distribution range of freshwater zooplankton than previously thought. This study is the first to broadly explore the metazoan biodiversity of freshwater systems with DNA barcodes to construct a reference library that represents the first step for future programs which aim to monitor ecosystem health, track invasive species, or improve knowledge of the ecology and distribution of freshwater zooplankton.}, } @article {pmid29531712, year = {2018}, author = {Tsuji, K and Ohgushi, T}, title = {Florivory indirectly decreases the plant reproductive output through changes in pollinator attraction.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2993-3001}, pmid = {29531712}, issn = {2045-7758}, abstract = {Species often interact indirectly with each other via their traits. There is increasing appreciation of trait-mediated indirect effects linking multiple interactions. Flowers interact with both pollinators and floral herbivores, and the flower-pollinator interaction may be modified by indirect effects of floral herbivores (i.e., florivores) on flower traits such as flower size attracting pollinators. To explore whether flower size affects the flower-pollinator interaction, we used Eurya japonica flowers. We examined whether artificial florivory decreased fruit and seed production, and also whether flower size affected florivory and the number of floral visitors. The petal removal treatment (i.e., artificial florivory) showed approximately 50% reduction in both fruit and seed set in natural pollination but not in artificial pollination. Furthermore, flower size increased the number of floral visitors, although it did not affect the frequency of florivory. Our results demonstrate that petal removal indirectly decreased 75% of female reproductive output via decreased flower visits by pollinators and that flower size mediated indirect interactions between florivory and floral visitors.}, } @article {pmid29531711, year = {2018}, author = {Bauwens, D and Claus, K and Mergeay, J}, title = {Genotyping validates photo-identification by the head scale pattern in a large population of the European adder (Vipera berus).}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2985-2992}, pmid = {29531711}, issn = {2045-7758}, abstract = {Capture-mark-recapture procedures are a basic tool in population studies and require that individual animals are correctly identified throughout their lifetime. A method that has become more and more popular uses photographic records of natural markings, such as pigmentation pattern and scalation configuration. As with any other marking tool, the validity of the photographic identification technique should be evaluated thoroughly. Here, we report on a large-scale double-marking study in which European adders (Vipera berus) were identified by both microsatellite genetic markers and by the pattern of head scalation. Samples that were successfully genotyped for all nine loci yielded 624 unique genotypes, which matched on a one-to-one basis with the individual assignments based on the head scalation pattern. Thus, adders considered as different individuals by their genotypes were also identified as different individuals by their head scalation pattern, and vice versa. Overall, variation in the numbers, shape, and arrangement of the head scales enabled us to distinguish among 3200+ photographed individual snakes. Adders that were repeatedly sequenced genetically over intervals of 2-3 years showed no indication whatsoever for a change in the head scale pattern. Photographic records of 900+ adders that were recaptured over periods of up to 12 years showed a very detailed and precise match of the head scale characteristics. These natural marks are thus robust over time and do not change during an individual's lifetime. With very low frequency (0.3%), we detected small changes in scalation that were readily discernible and could be attributed to physical injury or infection. Our study provides a conclusive validation for the use of photo-identification by head scale patterns in the European adder.}, } @article {pmid29531710, year = {2018}, author = {Fan, B and McHugh, AD and Guo, S and Ma, Q and Zhang, J and Zhang, X and Zhang, W and Du, J and Yu, Q and Zhao, C}, title = {Factors influencing the natural regeneration of the pioneering shrub Calligonum mongolicum in sand dune stabilization plantations in arid deserts of northwest China.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2975-2984}, pmid = {29531710}, issn = {2045-7758}, abstract = {Calligonum mongolicum is a successful pioneer shrub to combat desertification, which is widely used for vegetation restoration in the desert regions of northwest China. In order to reveal the limitations to natural regeneration of C. mongolicum by asexual and sexual reproduction, following the process of sand dune stabilization, we assessed clonal shoots, seedling emergence, soil seed bank density, and soil physical characteristics in mobile and stabilized sand dunes. Controlled field and pot experiments were also conducted to assess germination and seedling emergence in different dune soil types and seed burial depths. The population density of mature C. mongolicum was significantly different after sand dune stabilization. Juvenile density of C. mongolicm was much lower in stabilized sand dunes than mobile sand dune. There was no significant difference in soil seed bank density at three soil depths between mobile and stabilized sand dunes, while the emergence of seedlings in stabilized dunes was much lower than emergence in mobile dunes. There was no clonal propagation found in stabilized dunes, and very few C. mongolicum seedlings were established on stabilized sand dunes. Soil clay and silt content, air-filled porosity, and soil surface compaction were significantly changed from mobile sand dune to stabilized dunes. Seedling emergence of C. mongolicm was highly dependent on soil physical condition. These results indicated that changes in soil physical condition limited clonal propagation and seedling emergence of C. mongolicum in stabilized sand dunes. Seed bank density was not a limiting factor; however, poor seedling establishment limited C. mongolicum's further natural regeneration in stabilized sand dunes. Therefore, clonal propagation may be the most important mode for population expansion in mobile sand dunes. As a pioneer species C. mongolicum is well adapted to propagate in mobile sand dune conditions, it appears unlikely to survive naturally in stabilized sand dune plantations.}, } @article {pmid29531709, year = {2018}, author = {Becher, PG and Hagman, A and Verschut, V and Chakraborty, A and Rozpędowska, E and Lebreton, S and Bengtsson, M and Flick, G and Witzgall, P and Piškur, J}, title = {Chemical signaling and insect attraction is a conserved trait in yeasts.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2962-2974}, pmid = {29531709}, issn = {2045-7758}, abstract = {Yeast volatiles attract insects, which apparently is of mutual benefit, for both yeasts and insects. However, it is unknown whether biosynthesis of metabolites that attract insects is a basic and general trait, or if it is specific for yeasts that live in close association with insects. Our goal was to study chemical insect attractants produced by yeasts that span more than 250 million years of evolutionary history and vastly differ in their metabolism and lifestyle. We bioassayed attraction of the vinegar fly Drosophila melanogaster to odors of phylogenetically and ecologically distinct yeasts grown under controlled conditions. Baker's yeast Saccharomyces cerevisiae, the insect-associated species Candida californica, Pichia kluyveri and Metschnikowia andauensis, wine yeast Dekkera bruxellensis, milk yeast Kluyveromyces lactis, the vertebrate pathogens Candida albicans and Candida glabrata, and oleophilic Yarrowia lipolytica were screened for fly attraction in a wind tunnel. Yeast headspace was chemically analyzed, and co-occurrence of insect attractants in yeasts and flowering plants was investigated through a database search. In yeasts with known genomes, we investigated the occurrence of genes involved in the synthesis of key aroma compounds. Flies were attracted to all nine yeasts studied. The behavioral response to baker's yeast was independent of its growth stage. In addition to Drosophila, we tested the basal hexapod Folsomia candida (Collembola) in a Y-tube assay to the most ancient yeast, Y. lipolytica, which proved that early yeast signals also function on clades older than neopteran insects. Behavioral and chemical data and a search for selected genes of volatile metabolites underline that biosynthesis of chemical signals is found throughout the yeast clade and has been conserved during the evolution of yeast lifestyles. Literature and database reviews corroborate that yeast signals mediate mutualistic interactions between insects and yeasts. Moreover, volatiles emitted by yeasts are commonly found also in flowers and attract many insect species. The collective evidence suggests that the release of volatile signals by yeasts is a widespread and phylogenetically ancient trait, and that insect-yeast communication evolved prior to the emergence of flowering plants. Co-occurrence of the same attractant signals in yeast and flowers suggests that yeast-insect communication may have contributed to the evolution of insect-mediated pollination in flowers.}, } @article {pmid29531708, year = {2018}, author = {Wu, N and Qu, Y and Guse, B and Makarevičiūtė, K and To, S and Riis, T and Fohrer, N}, title = {Hydrological and environmental variables outperform spatial factors in structuring species, trait composition, and beta diversity of pelagic algae.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2947-2961}, pmid = {29531708}, issn = {2045-7758}, abstract = {There has been increasing interest in algae-based bioassessment, particularly, trait-based approaches are increasingly suggested. However, the main drivers, especially the contribution of hydrological variables, of species composition, trait composition, and beta diversity of algae communities are less studied. To link species and trait composition to multiple factors (i.e., hydrological variables, local environmental variables, and spatial factors) that potentially control species occurrence/abundance and to determine their relative roles in shaping species composition, trait composition, and beta diversities of pelagic algae communities, samples were collected from a German lowland catchment, where a well-proven ecohydrological modeling enabled to predict long-term discharges at each sampling site. Both trait and species composition showed significant correlations with hydrological, environmental, and spatial variables, and variation partitioning revealed that the hydrological and local environmental variables outperformed spatial variables. A higher variation of trait composition (57.0%) than species composition (37.5%) could be explained by abiotic factors. Mantel tests showed that both species and trait-based beta diversities were mostly related to hydrological and environmental heterogeneity with hydrological contributing more than environmental variables, while purely spatial impact was less important. Our findings revealed the relative importance of hydrological variables in shaping pelagic algae community and their spatial patterns of beta diversities, emphasizing the need to include hydrological variables in long-term biomonitoring campaigns and biodiversity conservation or restoration. A key implication for biodiversity conservation was that maintaining the instream flow regime and keeping various habitats among rivers are of vital importance. However, further investigations at multispatial and temporal scales are greatly needed.}, } @article {pmid29531707, year = {2018}, author = {Sands, B and Mgidiswa, N and Nyamukondiwa, C and Wall, R}, title = {Environmental consequences of deltamethrin residues in cattle feces in an African agricultural landscape.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2938-2946}, pmid = {29531707}, issn = {2045-7758}, abstract = {Pyrethroid insecticides are widely used to control ectoparasites of livestock, particularly ticks and biting flies. Their use in African livestock systems is increasing, driven by the need to increase productivity and local food security. However, insecticide residues present in the dung after treatment are toxic to dung-inhabiting insects. In a semiarid agricultural habitat in Botswana, dung beetle adult mortality, brood ball production, and larval survival were compared between untreated cattle dung and cattle dung spiked with deltamethrin, to give concentrations of 0.01, 0.1, 0.5, or 1 ppm. Cattle dung-baited pitfall traps were used to measure repellent effects of deltamethrin in dung on Scarabaeidae. Dung decomposition rate was also examined. There was significantly increased mortality of adult dung beetles colonizing pats that contained deltamethrin compared to insecticide-free pats. Brood ball production was significantly reduced at concentrations of 1 ppm; larval survival was significantly reduced in dung containing 0.1 ppm deltamethrin and above. There was no difference in the number of Scarabaeidae attracted to dung containing any of the deltamethrin concentrations. Dung decomposition was significantly reduced even at the lowest concentration (0.01 ppm) compared to insecticide-free dung. The widespread use of deltamethrin in African agricultural ecosystems is a significant cause for concern; sustained use is likely to damage dung beetle populations and their provision of environmentally and economically important ecosystem services. Contaminated dung buried by paracoprid (tunneling) beetles may retain insecticidal effects, with impacts on developing larvae below ground. Lethal and sublethal effects on entire dung beetle (Scarabaeidae) communities could impair ecosystem function in agricultural landscapes.}, } @article {pmid29531706, year = {2018}, author = {Comeault, AA}, title = {The genomic and ecological context of hybridization affects the probability that symmetrical incompatibilities drive hybrid speciation.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2926-2937}, pmid = {29531706}, issn = {2045-7758}, abstract = {Despite examples of homoploid hybrid species, theoretical work describing when, where, and how we expect homoploid hybrid speciation to occur remains relatively rare. Here, I explore the probability of homoploid hybrid speciation due to "symmetrical incompatibilities" under different selective and genetic scenarios. Through simulation, I test how genetic architecture and selection acting on traits that do not themselves generate incompatibilities interact to affect the probability that hybrids evolve symmetrical incompatibilities with their parent species. Unsurprisingly, selection against admixture at "adaptive" loci that are linked to loci that generate incompatibilities tends to reduce the probability of evolving symmetrical incompatibilities. By contrast, selection that favors admixed genotypes at adaptive loci can promote the evolution of symmetrical incompatibilities. The magnitude of these outcomes is affected by the strength of selection, aspects of genetic architecture such as linkage relationships and the linear arrangement of loci along a chromosome, and the amount of hybridization following the formation of a hybrid zone. These results highlight how understanding the nature of selection, aspects of the genetics of traits affecting fitness, and the strength of reproductive isolation between hybridizing taxa can all be used to inform when we expect to observe homoploid hybrid speciation due to symmetrical incompatibilities.}, } @article {pmid29531705, year = {2018}, author = {Talenti, A and Dreger, DL and Frattini, S and Polli, M and Marelli, S and Harris, AC and Liotta, L and Cocco, R and Hogan, AN and Bigi, D and Caniglia, R and Parker, HG and Pagnacco, G and Ostrander, EA and Crepaldi, P}, title = {Studies of modern Italian dog populations reveal multiple patterns for domestic breed evolution.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2911-2925}, pmid = {29531705}, issn = {2045-7758}, abstract = {Through thousands of years of breeding and strong human selection, the dog (Canis lupus familiaris) exists today within hundreds of closed populations throughout the world, each with defined phenotypes. A singular geographic region with broad diversity in dog breeds presents an interesting opportunity to observe potential mechanisms of breed formation. Italy claims 14 internationally recognized dog breeds, with numerous additional local varieties. To determine the relationship among Italian dog populations, we integrated genetic data from 263 dogs representing 23 closed dog populations from Italy, seven Apennine gray wolves, and an established dataset of 161 globally recognized dog breeds, applying multiple genetic methods to characterize the modes by which breeds are formed within a single geographic region. Our consideration of each of five genetic analyses reveals a series of development events that mirror historical modes of breed formation, but with variations unique to the codevelopment of early dog and human populations. Using 142,840 genome-wide SNPs and a dataset of 1,609 canines, representing 182 breeds and 16 wild canids, we identified breed development routes for the Italian breeds that included divergence from common populations for a specific purpose, admixture of regional stock with that from other regions, and isolated selection of local stock with specific attributes.}, } @article {pmid29531704, year = {2018}, author = {Saarinen, K and Laakso, J and Lindström, L and Ketola, T}, title = {Adaptation to fluctuations in temperature by nine species of bacteria.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2901-2910}, pmid = {29531704}, issn = {2045-7758}, abstract = {Rapid environmental fluctuations are ubiquitous in the wild, yet majority of experimental studies mostly consider effects of slow fluctuations on organism. To test the evolutionary consequences of fast fluctuations, we conducted nine independent experimental evolution experiments with bacteria. Experimental conditions were same for all species, and we allowed them to evolve either in fluctuating temperature alternating rapidly between 20°C and 40°C or at constant 30°C temperature. After experimental evolution, we tested the performance of the clones in both rapid fluctuation and in constant environments (20°C, 30°C and 40°C). Results from experiments on these nine species were combined meta-analytically. We found that overall the clones evolved in the fluctuating environment had evolved better efficiency in tolerating fluctuations (i.e., they had higher yield in fluctuating conditions) than the clones evolved in the constant environment. However, we did not find any evidence that fluctuation-adapted clones would have evolved better tolerance to any measured constant environments (20°C, 30°C, and 40°C). Our results back up recent empirical findings reporting that it is hard to predict adaptations to fast fluctuations using tolerance curves.}, } @article {pmid29531703, year = {2018}, author = {Touzet, P and Villain, S and Buret, L and Martin, H and Holl, AC and Poux, C and Cuguen, J}, title = {Chloroplastic and nuclear diversity of wild beets at a large geographical scale: Insights into the evolutionary history of the Beta section.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2890-2900}, pmid = {29531703}, issn = {2045-7758}, abstract = {Historical demographic processes and mating systems are believed to be major factors in the shaping of the intraspecies genetic diversity of plants. Among Caryophyllales, the Beta section of the genus Beta, within the Amaranthaceae/Chenopodiaceae alliance, is an interesting study model with species and subspecies (Beta macrocarpa, Beta patula, Beta vulgaris maritima and B.v. adanensis) differing in geographical distribution and mating system. In addition, one of the species, B. macrocarpa, mainly diploid, varies in its level of ploidy with a tetraploid cytotype described in the Canary Islands and in Portugal. In this study, we analyzed the nucleotide diversity of chloroplastic and nuclear sequences on a representative sampling of species and subspecies of the Beta section (except B. patula). Our objectives were (1) to assess their genetic relationships through phylogenetic and multivariate analyses, (2) relate their genetic diversity to their mating system, and (3) reconsider the ploidy status and the origin of the Canarian Beta macrocarpa.}, } @article {pmid29531702, year = {2018}, author = {Folt, B and Donnelly, MA and Guyer, C}, title = {Spatial patterns of the frog Oophaga pumilio in a plantation system are consistent with conspecific attraction.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2880-2889}, pmid = {29531702}, issn = {2045-7758}, abstract = {The conspecific attraction hypothesis predicts that individuals are attracted to conspecifics because conspecifics may be cues to quality habitat and/or colonists may benefit from living in aggregations. Poison frogs (Dendrobatidae) are aposematic, territorial, and visually oriented-three characteristics which make dendrobatids an appropriate model to test for conspecific attraction. In this study, we tested this hypothesis using an extensive mark-recapture dataset of the strawberry poison frog (Oophaga pumilio) from La Selva Biological Station, Costa Rica. Data were collected from replicate populations in a relatively homogenous Theobroma cacao plantation, which provided a unique opportunity to test how conspecifics influence the spatial ecology of migrants in a controlled habitat with homogenous structure. We predicted that (1) individuals entering a population would aggregate with resident adults, (2) migrants would share sites with residents at a greater frequency than expected by chance, and (3) migrant home ranges would have shorter nearest-neighbor distances (NND) to residents than expected by chance. The results were consistent with these three predictions: Relative to random simulations, we observed significant aggregation, home-range overlap, and NND distribution functions in four, five, and six, respectively, of the six migrant-resident groups analyzed. Conspecific attraction may benefit migrant O. pumilio by providing cues to suitable home sites and/or increasing the potential for social interactions with conspecifics; if true, these benefits should outweigh the negative effects of other factors associated with aggregation. The observed aggregation between migrant and resident O. pumilio is consistent with conspecific attraction in dendrobatid frogs, and our study provides rare support from a field setting that conspecific attraction may be a relevant mechanism for models of anuran spatial ecology.}, } @article {pmid29531701, year = {2018}, author = {Carlson, LG and Beard, KH and Adler, PB}, title = {Direct effects of warming increase woody plant abundance in a subarctic wetland.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2868-2879}, pmid = {29531701}, issn = {2045-7758}, abstract = {Both the direct effects of warming on a species' vital rates and indirect effects of warming caused by interactions with neighboring species can influence plant populations. Furthermore, herbivory mediates the effects of warming on plant community composition in many systems. Thus, determining the importance of direct and indirect effects of warming, while considering the role of herbivory, can help predict long-term plant community dynamics. We conducted a field experiment in the coastal wetlands of western Alaska to investigate how warming and herbivory influence the interactions and abundances of two common plant species, a sedge, Carex ramenskii, and a dwarf shrub, Salix ovalifolia. We used results from the experiment to model the equilibrium abundances of the species under different warming and grazing scenarios and to determine the contribution of direct and indirect effects to predict population changes. Consistent with the current composition of the landscape, model predictions suggest that Carex is more abundant than Salix under ambient temperatures with grazing (53% and 27% cover, respectively). However, with warming and grazing, Salix becomes more abundant than Carex (57% and 41% cover, respectively), reflecting both a negative response of Carex and a positive response of Salix to warming. While grazing reduced the cover of both species, herbivory did not prevent a shift in dominance from sedges to the dwarf shrub. Direct effects of climate change explained about 97% of the total predicted change in species cover, whereas indirect effects explained only 3% of the predicted change. Thus, indirect effects, mediated by interactions between Carex and Salix, were negligible, likely due to use of different niches and weak interspecific interactions. Results suggest that a 2°C increase could cause a shift in dominance from sedges to woody plants on the coast of western Alaska over decadal timescales, and this shift was largely a result of the direct effects of warming. Models predict this shift with or without goose herbivory. Our results are consistent with other studies showing an increase in woody plant abundance in the Arctic and suggest that shifts in plant-plant interactions are not driving this change.}, } @article {pmid29531700, year = {2018}, author = {Yukilevich, R and Maroja, LS and Nguyen, K and Hussain, S and Kumaran, P}, title = {Rapid sexual and genomic isolation in sympatric Drosophila without reproductive character displacement.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2852-2867}, pmid = {29531700}, issn = {2045-7758}, abstract = {The rapid evolution of sexual isolation in sympatry has long been associated with reinforcement (i.e., selection to avoid maladaptive hybridization). However, there are many species pairs in sympatry that have evolved rapid sexual isolation without known costs to hybridization. A major unresolved question is what evolutionary processes are involved in driving rapid speciation in such cases. Here, we focus on one such system; the Drosophila athabasca species complex, which is composed of three partially sympatric and interfertile semispecies: WN, EA, and EB. To study speciation in this species complex, we assayed sexual and genomic isolation within and between these semispecies in both sympatric and allopatric populations. First, we found no evidence of reproductive character displacement (RCD) in sympatric zones compared to distant allopatry. Instead, semispecies were virtually completely sexually isolated from each other across their entire ranges. Moreover, using spatial approaches and coalescent demographic simulations, we detected either zero or only weak heterospecific gene flow in sympatry. In contrast, within each semispecies we found only random mating and little population genetic structure, except between highly geographically distant populations. Finally, we determined that speciation in this system is at least an order of magnitude older than previously assumed, with WN diverging first, around 200K years ago, and EA and EB diverging 100K years ago. In total, these results suggest that these semispecies should be given full species status and we adopt new nomenclature: WN-D. athabasca, EA-D. mahican, and EB-D. lenape. While the lack of RCD in sympatry and interfertility do not support reinforcement, we discuss what additional evidence is needed to further decipher the mechanisms that caused rapid speciation in this species complex.}, } @article {pmid29531699, year = {2018}, author = {Young, Y and Buckiewicz, N and Long, TAF}, title = {Nutritional geometry and fitness consequences in Drosophila suzukii, the Spotted-Wing Drosophila.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2842-2851}, pmid = {29531699}, issn = {2045-7758}, abstract = {Since its arrival to North America less than a decade ago, the invasive Spotted-Wing Drosophila (Drosophila suzukii) has inflicted substantial economic losses on soft fruit agriculture due to its ability to oviposit into ripening fruits. More effective management approaches for this species are needed, but little is known about the factors that influence behavioral choices made by D. suzukii when selecting hosts, or the consequences that their offspring experience when developing in different environments. Using a nutritional geometry methodology, we found that the ratio of proteins-to-carbohydrates (P:C) present in media greatly influenced adult D. suzukii behavior and subsequent offspring development. Whereas adult flies showed a strong bias in their oviposition and association behaviors toward carbohydrate-rich foods, larval survival and eclosion rate were strongly dependent on protein availability. Here, we explore the preference-performance hypothesis (PPH), in which females are predicted to oviposit on medias that provide the greatest offspring benefits, in regard to its relevance in D. suzukii behavior and consequences for management. Our results provide valuable insight into the ecology and evolution of this species that may hopefully lead to more effective management strategies.}, } @article {pmid29531698, year = {2018}, author = {Van Wyngaarden, M and Snelgrove, PVR and DiBacco, C and Hamilton, LC and Rodríguez-Ezpeleta, N and Zhan, L and Beiko, RG and Bradbury, IR}, title = {Oceanographic variation influences spatial genomic structure in the sea scallop, Placopecten magellanicus.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2824-2841}, pmid = {29531698}, issn = {2045-7758}, abstract = {Environmental factors can influence diversity and population structure in marine species and accurate understanding of this influence can both improve fisheries management and help predict responses to environmental change. We used 7163 SNPs derived from restriction site-associated DNA sequencing genotyped in 245 individuals of the economically important sea scallop, Placopecten magellanicus, to evaluate the correlations between oceanographic variation and a previously identified latitudinal genomic cline. Sea scallops span a broad latitudinal area (>10 degrees), and we hypothesized that climatic variation significantly drives clinal trends in allele frequency. Using a large environmental dataset, including temperature, salinity, chlorophyll a, and nutrient concentrations, we identified a suite of SNPs (285-621, depending on analysis and environmental dataset) potentially under selection through correlations with environmental variation. Principal components analysis of different outlier SNPs and environmental datasets revealed similar northern and southern clusters, with significant associations between the first axes of each (R2adj = .66-.79). Multivariate redundancy analysis of outlier SNPs and the environmental principal components indicated that environmental factors explained more than 32% of the variance. Similarly, multiple linear regressions and random-forest analysis identified winter average and minimum ocean temperatures as significant parameters in the link between genetic and environmental variation. This work indicates that oceanographic variation is associated with the observed genomic cline in this species and that seasonal periods of extreme cold may restrict gene flow along a latitudinal gradient in this marine benthic bivalve. Incorporating this finding into management may improve accuracy of management strategies and future predictions.}, } @article {pmid29531697, year = {2018}, author = {Champagne, E and Moore, BD and Côté, SD and Tremblay, JP}, title = {Spatial correlations between browsing on balsam fir by white-tailed deer and the nutritional value of neighboring winter forage.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2812-2823}, pmid = {29531697}, issn = {2045-7758}, abstract = {Associational effects, that is, the influence of neighboring plants on herbivory suffered by a plant, are an outcome of forage selection. Although forage selection is a hierarchical process, few studies have investigated associational effects at multiple spatial scales. Because the nutritional quality of plants can be spatially structured, it might differently influence associational effects across multiple scales. Our objective was to determine the radius of influence of neighbor density and nutritional quality on balsam fir (Abies balsamea) herbivory by white-tailed deer (Odocoileus virginianus) in winter. We quantified browsing rates on fir and the density and quality of neighboring trees in a series of 10-year-old cutovers on Anticosti Island (Canada). We used cross-correlations to investigate relationships between browsing rates and the density and nutritional quality of neighboring trees at distances up to 1,000 m. Balsam fir and white spruce (Picea glauca) fiber content and dry matter in vitro true digestibility were correlated with fir browsing rate at the finest extra-patch scale (across distance of up to 50 m) and between cutover areas (300-400 m). These correlations suggest associational effects, that is, low nutritional quality of neighbors reduces the likelihood of fir herbivory (associational defense). Our results may indicate associational effects mediated by intraspecific variation in plant quality and suggest that these effects could occur at scales from tens to hundreds of meters. Understanding associational effects could inform strategies for restoration or conservation; for example, planting of fir among existing natural regeneration could be concentrated in areas of low nutritional quality.}, } @article {pmid29531696, year = {2018}, author = {Sleith, RS and Wehr, JD and Karol, KG}, title = {Untangling climate and water chemistry to predict changes in freshwater macrophyte distributions.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2802-2811}, pmid = {29531696}, issn = {2045-7758}, abstract = {Forecasting changes in the distributions of macrophytes is essential to understanding how aquatic ecosystems will respond to climate and environmental changes. Previous work in aquatic ecosystems has used climate data at large scales and chemistry data at small scales; the consequence of using these different data types has not been evaluated. This study combines a survey of macrophyte diversity and water chemistry measurements at a large regional scale to demonstrate the feasibility and necessity of including ecological measurements, in addition to climate data, in species distribution models of aquatic macrophytes. A survey of 740 water bodies stratified across 327,000 square kilometers was conducted to document Characeae (green macroalgae) species occurrence and water chemistry data. Chemistry variables and climate data were used separately and in concert to develop species distribution models for ten species across the study area. The impacts of future environmental changes on species distributions were modeled using a range of global climate models (GCMs), representative concentration pathways (RCPs), and pollution scenarios. Models developed with chemistry variables generally gave the most accurate predictions of species distributions when compared with those using climate variables. Calcium and conductivity had the highest total relative contribution to models across all species. Habitat changes were most pronounced in scenarios with increased road salt and deicer influences, with two species predicted to increase in range by >50% and four species predicted to decrease in range by >50%. Species of Characeae have distinct habitat ranges that closely follow spatial patterns of water chemistry. Species distribution models built with climate data alone were insufficient to predict changes in distributions in the study area. The development and implementation of standardized, large-scale water chemistry databases will aid predictions of habitat changes for aquatic ecosystems.}, } @article {pmid29531695, year = {2018}, author = {Briscoe, DK and Fossette, S and Scales, KL and Hazen, EL and Bograd, SJ and Maxwell, SM and McHuron, EA and Robinson, PW and Kuhn, C and Costa, DP and Crowder, LB and Lewison, RL}, title = {Characterizing habitat suitability for a central-place forager in a dynamic marine environment.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2788-2801}, pmid = {29531695}, issn = {2045-7758}, abstract = {Characterizing habitat suitability for a marine predator requires an understanding of the environmental heterogeneity and variability over the range in which a population moves during a particular life cycle. Female California sea lions (Zalophus californianus) are central-place foragers and are particularly constrained while provisioning their young. During this time, habitat selection is a function of prey availability and proximity to the rookery, which has important implications for reproductive and population success. We explore how lactating females may select habitat and respond to environmental variability over broad spatial and temporal scales within the California Current System. We combine near-real-time remotely sensed satellite oceanography, animal tracking data (n = 72) from November to February over multiple years (2003-2009) and Generalized Additive Mixed Models (GAMMs) to determine the probability of sea lion occurrence based on environmental covariates. Results indicate that sea lion presence is associated with cool (<14°C), productive waters, shallow depths, increased eddy activity, and positive sea-level anomalies. Predictive habitat maps generated from these biophysical associations suggest winter foraging areas are spatially consistent in the nearshore and offshore environments, except during the 2004-2005 winter, which coincided with an El Niño event. Here, we show how a species distribution model can provide broadscale information on the distribution of female California sea lions during an important life history stage and its implications for population dynamics and spatial management.}, } @article {pmid29531694, year = {2018}, author = {Goga, M and Ručová, D and Kolarčik, V and Sabovljević, M and Bačkor, M and Lang, I}, title = {Usnic acid, as a biotic factor, changes the ploidy level in mosses.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2781-2787}, pmid = {29531694}, issn = {2045-7758}, abstract = {Lichens and mosses often share the same environmental conditions where they compete for substrate and other essential factors. Lichens use secondary metabolites as allelochemicals to repel surrounding plants and potential rivals. In mosses, endoreduplication leads to the occurrence of various ploidy levels in the same individual and has been suggested as an adaptation to abiotic stresses. Here, we show that also biotic factors such as usnic acid, an allelochemical produced by lichens, directly influenced the level of ploidy in mosses. Application of usnic acid changed the nuclei proportion and significantly enhanced the endoreduplication index in two moss species, Physcomitrella patens and Pohlia drummondii. These investigations add a new aspect on secondary metabolites of lichens which count as biotic factors and affect ploidy levels in mosses.}, } @article {pmid29531693, year = {2018}, author = {Graignic, N and Tremblay, F and Bergeron, Y}, title = {Influence of northern limit range on genetic diversity and structure in a widespread North American tree, sugar maple (Acer saccharum Marshall).}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2766-2780}, pmid = {29531693}, issn = {2045-7758}, abstract = {Due to climate change, the ranges of many North American tree species are expected to shift northward. Sugar maple (Acer saccharum Marshall) reaches its northern continuous distributional limit in northeastern North America at the transition between boreal mixed-wood and temperate deciduous forests. We hypothesized that marginal fragmented northern populations from the boreal mixed wood would have a distinct pattern of genetic structure and diversity. We analyzed variation at 18 microsatellite loci from 23 populations distributed along three latitudinal transects (west, central, and east) that encompass the continuous-discontinuous species range. Each transect was divided into two zones, continuous (temperate deciduous) and discontinuous (boreal mixed wood), based on sugar maple stand abundance. Respective positive and negative relationships were found between the distance of each population to the northern limit (D_north), and allelic richness (AR) and population differentiation (FST). These relations were tested for each transect separately; the pattern (discontinuous-continuous) remained significant only for the western transect. structure analysis revealed the presence of four clusters. The most northern populations of each transect were assigned to a distinct group. Asymmetrical gene flow occurred from the southern into the four northernmost populations. Southern populations in Québec may have originated from two different postglacial migration routes. No evidence was found to validate the hypothesis that northern populations were remnants of a larger population that had migrated further north of the species range after the retreat of the ice sheet. The northernmost sugar maple populations possibly originated from long-distance dispersal.}, } @article {pmid29531692, year = {2018}, author = {Cherel, Y and Parenteau, C and Bustamante, P and Bost, CA}, title = {Stable isotopes document the winter foraging ecology of king penguins and highlight connectivity between subantarctic and Antarctic ecosystems.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2752-2765}, pmid = {29531692}, issn = {2045-7758}, abstract = {The poorly known winter foraging ecology of the king penguin, a major Southern Ocean consumer, was investigated at the subantarctic Crozet Islands where the largest global population breeds. Blood δ13C and δ15N values were used as proxies of the birds' foraging habitat and diet, respectively, and circulating prolactin levels helped in determining the birds' reproductive status. Plasma prolactin concentrations showed that king penguin adults of unknown breeding status (n = 52) that were present at the colony in winter were in fact breeders and failed breeders, but were not non -breeders. Circulating prolactin was neither related to δ13C nor δ15N values, thus suggesting that both breeders and failed breeders used the same foraging habitats and fed on the same prey. Plasma and blood cell isotopic values depicted four new relevant biological features on the feeding strategies of king penguins during the critical winter period: (1) 42% of the birds foraged in the distant Antarctic Zone, but 58% fed primarily in subantarctic waters (δ13C), (2) they preyed upon myctophids in both zones (δ15N), (3) individuals were consistent in their foraging strategies over the winter months (δ13C and δ15N), and (4) a higher proportion of females (77%-80%) than males (27%-31%) favored feeding in distant Antarctic waters (δ13C). This study highlights trophic connectivity between subantarctic and Antarctic ecosystems and hence the key role of energy export from Antarctic waters to sustain breeding populations of subantarctic predators, including during the Austral winter.}, } @article {pmid29531691, year = {2018}, author = {Dillon, RT}, title = {Volatility in the effective size of a freshwater gastropod population.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2746-2751}, pmid = {29531691}, issn = {2045-7758}, abstract = {Despite the utility of gastropod models for the study of evolutionary processes of great generality and importance, their effective population size has rarely been estimated in the field. Here, we report allele frequency variance at three allozyme-encoding loci monitored over 7 years in a population of the invasive freshwater pulmonate snail Physa acuta (Draparnaud 1805), estimating effective population size with both single-sample and two-sample approaches. Estimated Ne declined from effectively infinite in 2009 to approximately 40-50 in 2012 and then rose back to infinity in 2015, corresponding to a striking fluctuation in the apparent census size of the population. Such volatility in Ne may reflect cryptic population subdivision.}, } @article {pmid29531690, year = {2018}, author = {Wollebaek, J and Heggenes, J and Roed, KH}, title = {Life histories and ecotype conservation in an adaptive vertebrate: Genetic constitution of piscivorous brown trout covaries with habitat stability.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2729-2745}, pmid = {29531690}, issn = {2045-7758}, abstract = {Ecotype variation in species exhibiting different life history strategies may reflect heritable adaptations to optimize reproductive success, and potential for speciation. Traditionally, ecotypes have, however, been defined by morphometrics and life history characteristics, which may be confounded with individual plasticity. Here, we use the widely distributed and polytypic freshwater fish species brown trout (Salmo trutta) as a model to study piscivorous life history and its genetic characteristics in environmentally contrasting habitats; a large lake ecosystem with one major large and stable tributary, and several small tributaries. Data from 550 fish and 13 polymorphic microsatellites (He = 0.67) indicated ecotype-specific genetic differentiation (θ = 0.0170, p < .0001) among Bayesian assigned small riverine resident and large, lake migrating brown trout (>35 cm), but only in the large tributary. In contrast, large trout did not constitute a distinct genetic group in small tributaries, or across riverine sites. Whereas life history data suggest a small, river resident and a large migratory piscivorous ecotype in all studied tributaries, genetic data indicated that a genetically distinct piscivorous ecotype is more likely to evolve in the large and relatively more stable river habitat. In the smaller tributaries, ecotypes apparently resulted from individual plasticity. Whether different life histories and ecotypes result from individual plasticity or define different genetic types, have important consequence for conservation strategies.}, } @article {pmid29531689, year = {2018}, author = {Eikenaar, C and Isaksson, C and Hegemann, A}, title = {A hidden cost of migration? Innate immune function versus antioxidant defense.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2721-2728}, pmid = {29531689}, issn = {2045-7758}, abstract = {Migration is energetically demanding and physiologically challenging. Migrating birds, for example, need to boost their antioxidant defenses to defeat the pro-oxidants produced during high energetic activity. The enhanced antioxidant defense possibly withdraws limited resources (e.g., energy or micronutrients) from other physiological functions, such as immune defense. Such a trade-off might not occur outside the migration seasons or in resident individuals. Here, we investigate whether there is a negative relationship between innate immune function and antioxidant defense by sampling both migrating and resident blackbirds (Turdus merula) at the same location during the same period of the annual cycle. We show that in migrating blackbirds microbial killing capacity (BKA), an integrative measure of baseline innate immune function was negatively correlated with total nonenzymatic antioxidant capacity. In contrast, in resident conspecifics, sampled at the same time and location, these two physiological measures were not correlated. This suggests that migrating birds trade off innate immune function and antioxidant defense. Furthermore, and likely a consequence of this trade-off, in migrant blackbirds BKA was positively correlated with oxidative damage to lipids. In resident blackbirds BKA and degree of lipid oxidation were uncorrelated. The mechanism and currencies of the supposed trade-off are currently unknown, but energetic investments or micronutrients are likely candidates. Future experimental studies could provide more conclusive evidence for this trade-off; yet, our results open up a new level of thinking about the physiological costs of migration.}, } @article {pmid29531688, year = {2018}, author = {He, X and Luo, K and Brown, C and Lin, L}, title = {A taxonomic, functional, and phylogenetic perspective on the community assembly of passerine birds along an elevational gradient in southwest China.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2712-2720}, pmid = {29531688}, issn = {2045-7758}, abstract = {Integrating multiple facets of biodiversity to describe spatial and temporal distribution patterns is one way of revealing the mechanisms driving community assembly. We assessed the species, functional, and phylogenetic composition and structure of passerine bird communities along an elevational gradient both in wintering and breeding seasons in the Ailao Mountains, southwest China, in order to identify the dominant ecological processes structuring the communities and how these processes change with elevation and season. Our research confirms that the highest taxonomic diversity, and distinct community composition, was found in the moist evergreen broadleaf forest at high elevation in both seasons. Environmental filtering was the dominant force at high elevations with relatively cold and wet climatic conditions, while the observed value of mean pairwise functional and phylogenetic distances of low elevation was constantly higher than expectation in two seasons, suggested interspecific competition could play the key role at low elevations, perhaps because of relative rich resource result from complex vegetation structure and human-induced disturbance. Across all elevations, there was a trend of decreasing intensity of environmental filtering whereas increasing interspecific competition from wintering season to breeding season. This was likely due to the increased resource availability but reproduction-associated competition in the summer months. In general, there is a clear justification for conservation efforts to protect entire elevational gradients in the Ailao Mountains, given the distinct taxonomic, functional, and phylogenetic compositions and also elevational migration pattern in passerine bird communities.}, } @article {pmid29531687, year = {2018}, author = {Burke, NW and Bonduriansky, R}, title = {The fitness effects of delayed switching to sex in a facultatively asexual insect.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2698-2711}, pmid = {29531687}, issn = {2045-7758}, abstract = {Facultative reproductive strategies that incorporate both sexual and parthenogenetic reproduction should be optimal, yet are rarely observed in animals. Resolving this paradox requires an understanding of the economics of facultative asexuality. Recent work suggests that switching from parthenogenesis to sex can be costly and that females can resist mating to avoid switching. However, it remains unclear whether these costs and resistance behaviors are dependent on female age. We addressed these questions in the Cyclone Larry stick insect, Sipyloidea larryi, by pairing females with males (or with females as a control) in early life prior to the start of parthenogenetic reproduction, or in mid- or late life after a period of parthenogenetic oviposition. Young females were receptive to mating even though mating in early life caused reduced fecundity. Female resistance to mating increased with age, but reproductive switching in mid- or late life did not negatively affect female survival or offspring performance. Overall, mating enhanced female fitness because fertilized eggs had higher hatching success and resulted in more adult offspring than parthenogenetic eggs. However, female fecundity and offspring viability were also enhanced in females paired with other females, suggesting a socially mediated maternal effect. Our results provide little evidence that switching from parthenogenesis to sex at any age is costly for S. larryi females. However, age-dependent effects of switching on some fitness components and female resistance behaviors suggest the possibility of context-dependent effects that may only be apparent in natural populations.}, } @article {pmid29531686, year = {2018}, author = {Peart, CR and Dasmahapatra, KK and Day, JJ}, title = {Contrasting geographic structure in evolutionarily divergent Lake Tanganyika catfishes.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2688-2697}, pmid = {29531686}, issn = {2045-7758}, abstract = {Geographic isolation is suggested to be among the most important processes in the generation of cichlid fish diversity in East Africa's Great Lakes, both through isolation by distance and fluctuating connectivity caused by changing lake levels. However, even broad scale phylogeographic patterns are currently unknown in many non-cichlid littoral taxa from these systems. To begin to address this, we generated restriction-site-associated DNA sequence (RADseq) data to investigate phylogeographic structure throughout Lake Tanganyika (LT) in two broadly sympatric rocky shore catfish species from independent evolutionary radiations with differing behaviors: the mouthbrooding claroteine, Lophiobagrus cyclurus, and the brood-parasite mochokid, Synodontis multipunctatus. Our results indicated contrasting patterns between these species, with strong lake-wide phylogeographic signal in L. cyclurus including a deep divergence between the northern and southern lake basins. Further structuring of these populations was observed across a heterogeneous habitat over much smaller distances. Strong population growth was observed in L. cyclurus sampled from shallow shorelines, suggesting population growth associated with the colonization of new habitats following lake-level rises. Conversely, S. multipunctatus, which occupies a broader depth range, showed little phylogeographic structure and lower rates of population growth. Our findings suggest that isolation by distance and/or habitat barriers may play a role in the divergence of non-cichlid fishes in LT, but this effect varies by species.}, } @article {pmid29531685, year = {2018}, author = {Taipale, SJ and Kahilainen, KK and Holtgrieve, GW and Peltomaa, ET}, title = {Simulated eutrophication and browning alters zooplankton nutritional quality and determines juvenile fish growth and survival.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2671-2687}, pmid = {29531685}, issn = {2045-7758}, abstract = {The first few months of life is the most vulnerable period for fish and their optimal hatching time with zooplankton prey is favored by natural selection. Traditionally, however, prey abundance (i.e., zooplankton density) has been considered important, whereas prey nutritional composition has been largely neglected in natural settings. High-quality zooplankton, rich in both essential amino acids (EAAs) and fatty acids (FAs), are required as starting prey to initiate development and fast juvenile growth. Prey quality is dependent on environmental conditions, and, for example, eutrophication and browning are two major factors defining primary producer community structures that will directly determine the nutritional quality of the basal food sources (algae, bacteria, terrestrial matter) for zooplankton. We experimentally tested how eutrophication and browning affect the growth and survival of juvenile rainbow trout (Oncorhynchus mykiss) by changing the quality of basal resources. We fed the fish on herbivorous zooplankton (Daphnia) grown with foods of different nutritional quality (algae, bacteria, terrestrial matter), and used GC-MS, stable isotope labeling as well as bulk and compound-specific stable isotope analyses for detecting the effects of different diets on the nutritional status of fish. The content of EAAs and omega-3 (ω-3) polyunsaturated FAs (PUFAs) in basal foods and zooplankton decreased in both eutrophication and browning treatments. The decrease in ω-3 PUFA and especially docosahexaenoic acid (DHA) was reflected to fish juveniles, but they were able to compensate for low availability of EAAs in their food. Therefore, the reduced growth and survival of the juvenile fish was linked to the low availability of DHA. Fish showed very low ability to convert alpha-linolenic acid (ALA) to DHA. We conclude that eutrophication and browning decrease the availability of the originally phytoplankton-derived DHA for zooplankton and juvenile fish, suggesting bottom-up regulation of food web quality.}, } @article {pmid29531684, year = {2018}, author = {Dysthe, JC and Rodgers, T and Franklin, TW and Carim, KJ and Young, MK and McKelvey, KS and Mock, KE and Schwartz, MK}, title = {Repurposing environmental DNA samples-detecting the western pearlshell (Margaritifera falcata) as a proof of concept.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2659-2670}, pmid = {29531684}, issn = {2045-7758}, abstract = {Information on the distribution of multiple species in a common landscape is fundamental to effective conservation and management. However, distribution data are expensive to obtain and often limited to high-profile species in a system. A recently developed technique, environmental DNA (eDNA) sampling, has been shown to be more sensitive than traditional detection methods for many aquatic species. A second and perhaps underappreciated benefit of eDNA sampling is that a sample originally collected to determine the presence of one species can be re-analyzed to detect additional taxa without additional field effort. We developed an eDNA assay for the western pearlshell mussel (Margaritifera falcata) and evaluated its effectiveness by analyzing previously collected eDNA samples that were annotated with information including sample location and deposited in a central repository. The eDNA samples were initially collected to determine habitat occupancy by nonbenthic fish species at sites that were in the vicinity of locations recently occupied by western pearlshell. These repurposed eDNA samples produced results congruent with historical western pearlshell surveys and permitted a more precise delineation of the extent of local populations. That a sampling protocol designed to detect fish was also successful for detecting a freshwater mussel suggests that rapidly accumulating collections of eDNA samples can be repurposed to enhance the efficiency and cost-effectiveness of aquatic biodiversity monitoring.}, } @article {pmid29531683, year = {2018}, author = {Ninua, L and Tarkhnishvili, D and Gvazava, E}, title = {Phylogeography and taxonomic status of trout and salmon from the Ponto-Caspian drainages, with inferences on European Brown Trout evolution and taxonomy.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2645-2658}, pmid = {29531683}, issn = {2045-7758}, abstract = {Current taxonomy of western Eurasian trout leaves a number of questions open; it is not clear to what extent some species are distinct genetically and morphologically. The purpose of this paper was to explore phylogeography and species boundaries in freshwater and anadromous trout from the drainages of the Black and the Caspian Seas (Ponto-Caspian). We studied morphology and mitochondrial phylogeny, combining samples from the western Caucasus within the potential range of five nominal species of trout that are thought to inhabit this region, and using the sequences available from GenBank. Our results suggest that the genetic diversity of trout in the Ponto-Caspian region is best explained with the fragmentation of catchments. (1) All trout species from Ponto-Caspian belong to the same mitochondrial clade, separated from the other trout since the Pleistocene; (2) the southeastern Black Sea area is the most likely place of diversification of this clade, which is closely related to the clades from Anatolia; (3) The species from the Black Sea and the Caspian Sea drainages are monophyletic; (4) except for the basal lineage of the Ponto-Caspian clade, Salmo rizeensis, all the lineages produce anadromous forms; (5) genetic diversification within the Ponto-Caspian clade is related to Pleistocene glacial waves; (6) the described morphological differences between the species are not fully diagnostic, and some earlier described differences depend on body size; the differences between freshwater and marine forms exceed those between the different lineages. We suggest a conservative taxonomic approach, using the names S. rizeensis and Salmo labrax for trout from the Black Sea basin and Salmo caspius and Salmo ciscaucasicus for the fish from the Caspian basin.}, } @article {pmid29531682, year = {2018}, author = {Harnik, PG and Maherali, H and Miller, JH and Manos, PS}, title = {Geographic range velocity and its association with phylogeny and life history traits in North American woody plants.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2632-2644}, pmid = {29531682}, issn = {2045-7758}, abstract = {The geographic ranges of taxa change in response to environmental conditions. Yet whether rates of range movement (biotic velocities) are phylogenetically conserved is not well known. Phylogenetic conservatism of biotic velocities could reflect similarities among related lineages in climatic tolerances and dispersal-associated traits. We assess whether late Quaternary biotic velocities were phylogenetically conserved and whether they correlate with climatic tolerances and dispersal-associated traits. We used phylogenetic regression and nonparametric correlation to evaluate associations between biotic velocities, dispersal-associated traits, and climatic tolerances for 28 woody plant genera and subgenera in North America. The velocities with which woody plant taxa shifted their core geographic range limits were positively correlated from time step to time step between 16 and 7 ka. The strength of this correlation weakened after 7 ka as the pace of climate change slowed. Dispersal-associated traits and climatic tolerances were not associated with biotic velocities. Although the biotic velocities of some genera were consistently fast and others consistently slow, biotic velocities were not phylogenetically conserved. The rapid late Quaternary range shifts of plants lacking traits that facilitate frequent long-distance dispersal has long been noted (i.e., Reid's Paradox). Our results are consistent with this paradox and show that it remains robust when phylogenetic information is taken into account. The lack of association between biotic velocities, dispersal-associated traits, and climatic tolerances may reflect several, nonmutually exclusive processes, including rare long-distance dispersal, biotic interactions, and cryptic refugia. Because late Quaternary biotic velocities were decoupled from dispersal-associated traits, trait data for genera and subgenera cannot be used to predict longer-term (millennial-scale) floristic responses to climate change.}, } @article {pmid29531681, year = {2018}, author = {Häkli, K and Østbye, K and Kahilainen, KK and Amundsen, PA and Præbel, K}, title = {Diversifying selection drives parallel evolution of gill raker number and body size along the speciation continuum of European whitefish.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2617-2631}, pmid = {29531681}, issn = {2045-7758}, abstract = {Adaptive radiation is the evolution of ecological and phenotypical diversity. It arises via ecological opportunity that promotes the exploration of underutilized or novel niches mediating specialization and reproductive isolation. The assumed precondition for rapid local adaptation is diversifying natural selection, but random genetic drift could also be a major driver of this process. We used 27 populations of European whitefish (Coregonus lavaretus) from nine lakes distributed in three neighboring subarctic watercourses in northern Fennoscandia as a model to test the importance of random drift versus diversifying natural selection for parallel evolution of adaptive phenotypic traits. We contrasted variation for two key adaptive phenotypic traits correlated with resource utilization of polymorphic fish; the number of gill rakers and the total length of fish, with the posterior distribution of neutral genetic differentiation from 13 microsatellite loci, to test whether the observed phenotypic divergence could be achieved by random genetic drift alone. Our results show that both traits have been under diversifying selection and that the evolution of these morphs has been driven by isolation through habitat adaptations. We conclude that diversifying selection acting on gill raker number and body size has played a significant role in the ongoing adaptive radiation of European whitefish morphs in this region.}, } @article {pmid29531680, year = {2018}, author = {Yu, T and Feng, Q and Si, J and Mitchell, PJ and Forster, MA and Zhang, X and Zhao, C}, title = {Depressed hydraulic redistribution of roots more by stem refilling than by nocturnal transpiration for Populus euphratica Oliv. in situ measurement.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2607-2616}, pmid = {29531680}, issn = {2045-7758}, abstract = {During the night, plant water loss can occur either through the roots, as hydraulic redistribution (HR), or through the leaves via the stoma, as nocturnal transpiration (En), which was methodologically difficult to separate from stem refilling (Re). While HR and En have been reported across a range of species, ecosystem, and climate zone, there is little understanding on the interactions between En and/or Re and HR. As water movement at night occurs via gradients of water potential, it is expected that during periods of high atmospheric vapor pressure deficit (VPD), water loss via En will override water loss via HR. To test this hypothesis, sap flow in stems and roots of Populus euphratica Oliv. trees, growing in a riparian zone in a hyperarid climate, was measured once in a year. Nocturnal stem sap flow was separated into En and Re using the "forecasted refilling" method. Substantial nocturnal sap flow (38% of 24-hr flux on average) was observed and positively correlated with VPD; however, the strength of the correlation was lower (R2 = .55) than diurnal sap flow (Ed) (R2 = .72), suggesting that nocturnal stem sap flow was attributed to both water loss through the canopy and replenishment of water in stem tissues. Partitioning of nocturnal sap flow shows that Re constituted approximately 80%, and En ~20%, of nocturnal sap flow. The amount of root sap flow attributed to redistribution was negatively related to Ed (R2 = .69) and the amount of acropetally sap flow in stems, Re (R2 = .41) and En (R2 = .14). It was suggested that the magnitude of HR is more strongly depressed by Re that was recharge to the water loss via Ed than by En. It was consistent with whole-tree water balance theory, that the nighttime upward sap flow to xylem, stem refilling and transpiration, may depress hydraulic redistribution of roots.}, } @article {pmid29531679, year = {2018}, author = {Lele, L and Ning, D and Cuiping, P and Xiao, G and Weihua, G}, title = {Genetic and epigenetic variations associated with adaptation to heterogeneous habitat conditions in a deciduous shrub.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2594-2606}, pmid = {29531679}, issn = {2045-7758}, abstract = {Environmentally induced phenotypic plasticity is thought to play an important role in the adaption of plant populations to heterogeneous habitat conditions, and yet the importance of epigenetic variation as a mechanism of adaptive plasticity in natural plant populations still merits further research. In this study, we investigated populations of Vitex negundo var. heterophylla (Chinese chastetree) from adjacent habitat types at seven sampling sites. Using several functional traits, we detected a significant differentiation between habitat types. With amplified fragment length polymorphisms (AFLP) and methylation-sensitive AFLP (MSAP), we found relatively high levels of genetic and epigenetic diversity but very low genetic and epigenetic differences between habitats within sites. Bayesian clustering showed a remarkable habitat-related differentiation and more genetic loci associated with the habitat type than epigenetic, suggesting that the adaptation to the habitat is genetically based. However, we did not find any significant correlation between genetic or epigenetic variation and habitat using simple and partial Mantel tests. Moreover, we found no correlation between genetic and ecologically relevant phenotypic variation and a significant correlation between epigenetic and phenotypic variation. Although we did not find any direct relationship between epigenetic variation and habitat environment, our findings suggest that epigenetic variation may complement genetic variation as a source of functional phenotypic diversity associated with adaptation to the heterogeneous habitat in natural plant populations.}, } @article {pmid29531678, year = {2018}, author = {Yuan, Z and Wei, B and Chen, Y and Jia, H and Wei, Q and Ye, Y}, title = {How do similarities in spatial distributions and interspecific associations affect the coexistence of Quercus species in the Baotianman National Nature Reserve, Henan, China.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2580-2593}, pmid = {29531678}, issn = {2045-7758}, abstract = {Congeneric species often have similar ecological characteristics and use similar resources. These similarities may make it easier for them to co-occur in a similar habitat but may also lead to strong competitions that limit their coexistence. Hence, how do similarities in congeneric species affect their coexistence exactly? This study mainly used spatial point pattern analysis in two 1 hm2 plots in the Baotianman National Nature Reserve, Henan, China, to compare the similarities in spatial distributions and interspecific associations of Quercus species. Results revealed that Quercus species were all aggregated under the complete spatial randomness null model, and aggregations were weaker under the heterogeneous Poisson process null model in each plot. The interspecific associations of Quercus species to non-Quercus species were very similar in Plot 1. However, they can be either positive or negative in different plots between the co-occurring Quercus species. The spatial distributions of congeneric species, interspecific associations with non-Quercus species, neighborhood richness around species, and species diversity were all different between the two plots. We found that congeneric species did have some similarities, and the closely related congeneric species can positive or negative associate with each other in different plots. The co-occurring congeneric species may have different survival strategies in different habitats. On the one hand, competition among congenerics may lead to differentiation in resource utilization. On the other hand, their similar interspecific associations can strengthen their competitive ability and promote local exclusion to noncongeneric species to obtain more living space. Our results provide new knowledge for us to better understand the coexistence mechanisms of species.}, } @article {pmid29531677, year = {2018}, author = {Billet, K and Genitoni, J and Bozec, M and Renault, D and Barloy, D}, title = {Aquatic and terrestrial morphotypes of the aquatic invasive plant, Ludwigia grandiflora, show distinct morphological and metabolomic responses.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2568-2579}, pmid = {29531677}, issn = {2045-7758}, abstract = {In the context of expansion of invasive species, survival of invasive plants is conditioned by their ability to adapt. In France, the water primrose Ludwigia grandiflora, an aquatic invasive species, invades yet wet meadows, leading to a depreciation of their fodder value. Understanding its potential adaption is necessary to its management, strong differences between both morphotypes were expected. So morphological and metabolic responses to terrestrial environment were analyzed for aquatic and terrestrial morphotypes. All morphological and biomass variables were greater in the terrestrial morphotype than the aquatic morphotype, independent of conditions. In terrestrial condition, both morphotypes showed a high production of sugars in root tissues, especially in the terrestrial morphotype and both morphotypes produced a low level of amino acids in shoot tissues. All results demonstrate that the terrestrial condition seems a stressful situation for both morphotypes, which activates glycolysis and fermentation pathways to improve their survival under hypoxic stress. But, only the terrestrial morphotype has been able to adjust its metabolism and maintain efficient growth. In the future, a differential transcriptomic analysis will be carried out to confirm this result.}, } @article {pmid29531676, year = {2018}, author = {Markevich, G and Esin, E and Anisimova, L}, title = {Basic description and some notes on the evolution of seven sympatric morphs of Dolly Varden Salvelinus malma from the Lake Kronotskoe Basin.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2554-2567}, pmid = {29531676}, issn = {2045-7758}, abstract = {The study examines the basic morphological and ecological features of Dolly Varden from Lake Kronotskoe (Russia, Kamchatka). Seven valid morphs different in head proportions, feeding, timing, and place of spawning have been determined in this ecosystem. The basic morphometric characteristics clearly separate Lake Kronotskoe morphs from each other, as well as from its potential ancestor (Dolly Varden). According to CVA analysis, the most notable morphological characteristics determining the mouth position are the length of a lower jaw and rostrum. Furthermore, five of seven morphs inhabit different depth zones of the lake and feed on different food resources. Our data suggest that reproductive isolation may be maintained by temporal/spatial isolation for two morphs with lacustrine spawning, and by spatial isolation only for the rest of the morphs with riverine spawning. The sympatric diversity of the Lake Kronotskoe charrs is exceptionally wide, and there are no other examples for seven sympatric morphs of genus Salvelinus to coexist within a single ecosystem. This study puts forward a three-step hypothetical model of charr divergence in Lake Kronotskoe as a potential ground for future studies.}, } @article {pmid29531675, year = {2018}, author = {Santonja, M and Pellan, L and Piscart, C}, title = {Macroinvertebrate identity mediates the effects of litter quality and microbial conditioning on leaf litter recycling in temperate streams.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2542-2553}, pmid = {29531675}, issn = {2045-7758}, abstract = {Plant litter decomposition is an essential ecosystem function that contributes to carbon and nutrient cycling in streams. Aquatic shredders, mainly macroinvertebrates, can affect this process in various ways; they consume leaf litter, breaking it down into fragments and creating suitable habitats or resources for other organisms through the production of fine particulate organic matter (FPOM). However, measures of litter-feeding traits across a wide range of aquatic macroinvertebrates are still rare. Here, we assessed the contributions of 11 species of freshwater macroinvertebrates to litter decomposition, by measuring consumption rate, FPOM production, and assimilation rate of highly decomposable (Alnus glutinosa) or poorly decomposable (Quercus robur) leaf litter types. In general, an increase in the quality of litter improved the litter consumption rate, and fungal conditioning of the leaf litter increased both the litter consumption rate and FPOM production. Macroinvertebrates specializing in leaf litter consumption also appeared to be the most sensitive to shifts in litter quality and the conditioning process. Contrary to expectations, the conditioning process did not increase the assimilation of low-quality litter. There was a strong correlation between the relative consumption rate (RCR) of the two litter types, and the relative FPOM production (RFP) was strongly correlated to the RCR. These findings suggest a consistent relationship between RCR and macroinvertebrate identity that is not affected by litter quality, and that the RFP could be inferred from the RCR. The varying responses of the macroinvertebrate feeding traits to litter quality and the conditioning process suggest that the replacement of a shredder invertebrate species by another species could have major consequences for the decomposition process and the detritus-based food web in streams. Further studies onto the importance of invertebrate identity and the effects of litter quality in a variety of freshwater ecosystems are needed to understand the whole ecosystem functioning and to predict its response to environmental changes.}, } @article {pmid29531674, year = {2018}, author = {Beasley, DE and Penick, CA and Boateng, NS and Menninger, HL and Dunn, RR}, title = {Urbanization disrupts latitude-size rule in 17-year cicadas.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2534-2541}, pmid = {29531674}, issn = {2045-7758}, abstract = {Many ectotherms show a decrease in body size with increasing latitude due to changes in climate, a pattern termed converse Bergmann's rule. Urban conditions-particularly warmer temperatures and fragmented landscapes-may impose stresses on development that could disrupt these body size patterns. To test the impact of urbanization on development and latitudinal trends in body size, we launched a citizen science project to collect periodical cicadas (Magicicada septendecim) from across their latitudinal range during the 2013 emergence of Brood II. Periodical cicadas are long-lived insects whose distribution spans a broad latitudinal range covering both urban and rural habitats. We used a geometric morphometric approach to assess body size and developmental stress based on fluctuating asymmetry in wing shape. Body size of rural cicadas followed converse Bergmann's rule, but this pattern was disrupted in urban habitats. In the north, urban cicadas were larger than their rural counterparts, while southern populations showed little variation in body size between habitats. We detected no evidence of differences in developmental stress due to urbanization. To our knowledge, this is the first evidence that urbanization disrupts biogeographical trends in body size, and this pattern highlights how the effects of urbanization may differ over a species' range.}, } @article {pmid29531673, year = {2018}, author = {Greimler, J and Schulze, CH and López Sepúlveda, P and Novoa, P and Gatica, A and Reiter, K and Wessely, J and Baeza, C and Peñailillo, P and Ruiz, E and Stuessy, T}, title = {Strong indication of an extinction-based saturation of the flora on the Pacific Robinson Crusoe Islands.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2527-2533}, pmid = {29531673}, issn = {2045-7758}, abstract = {Oceanic islands are vulnerable ecosystems and their flora has been under pressure since the arrival of the first humans. Human activities and both deliberately and inadvertently introduced biota have had and continue to have a severe impact on island endemic plants. The number of alien plants has increased nearly linearly on many islands, perhaps resulting in extinction-based saturation of island floras. Here, we provide evidence for such a scenario in Alejandro Selkirk, Robinson Crusoe Islands (Archipelago Juan Fernández, Chile). We compared species richness and species composition of historical vegetation samples from 1917 with recent ones from 2011. Changes in species' relative occurrence frequency were related to their taxonomic affiliation, dispersal mode, distribution status, and humidity and temperature preferences. While total species richness of vascular plants remained relatively similar, species composition changed significantly. Plants endemic to the Robinson Crusoe Islands declined, exotic species increased substantially within the period of ca. 100 years. Further, the relative occurrence frequency of plants with preferences for very warm and humid climate decreased, while the opposite was found for plants preferring drier and colder environments. Potential drivers responsible for this dramatic shift in the vegetation within only one century might have been the large goat population affecting especially small populations of endemic plants and climatic changes. Taking into account a substantial extinction debt, we expect further shifts in the vegetation of this small oceanic island toward alien plants. This would have significant negative consequences on global biodiversity, considering that island floras contribute substantially to global plant species richness due to their high proportion of endemics.}, } @article {pmid29531672, year = {2018}, author = {Hill, JE and DeVault, TL and Beasley, JC and Rhodes, OE and Belant, JL}, title = {Effects of vulture exclusion on carrion consumption by facultative scavengers.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2518-2526}, pmid = {29531672}, issn = {2045-7758}, abstract = {Vultures provide an essential ecosystem service through removal of carrion, but globally, many populations are collapsing and several species are threatened with extinction. Widespread declines in vulture populations could increase the availability of carrion to other organisms, but the ways facultative scavengers might respond to this increase have not been thoroughly explored. We aimed to determine whether facultative scavengers increase carrion consumption in the absence of vulture competition and whether they are capable of functionally replacing vultures in the removal of carrion biomass from the landscape. We experimentally excluded 65 rabbit carcasses from vultures during daylight hours and placed an additional 65 carcasses that were accessible to vultures in forested habitat in South Carolina, USA during summer (June-August). We used motion-activated cameras to compare carrion use by facultative scavenging species between the experimental and control carcasses. Scavenging by facultative scavengers did not increase in the absence of competition with vultures. We found no difference in scavenger presence between control carcasses and those from which vultures were excluded. Eighty percent of carcasses from which vultures were excluded were not scavenged by vertebrates, compared to 5% of carcasses that were accessible to vultures. At the end of the 7-day trials, there was a 10.1-fold increase in the number of experimental carcasses that were not fully scavenged compared to controls. Facultative scavengers did not functionally replace vultures during summer in our study. This finding may have been influenced by the time of the year in which the study took place, the duration of the trials, and the spacing of carcass sites. Our results suggest that under the warm and humid conditions of our study, facultative scavengers would not compensate for loss of vultures. Carcasses would persist longer in the environment and consumption of carrion would likely shift from vertebrates to decomposers. Such changes could have substantial implications for disease transmission, nutrient cycling, and ecosystem functioning.}, } @article {pmid29531671, year = {2018}, author = {Zellmer, AJ}, title = {Microgeographic morphological variation across larval wood frog populations associated with environment despite gene flow.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2504-2517}, pmid = {29531671}, issn = {2045-7758}, abstract = {Gene flow has historically been thought to constrain local adaptation; yet, recent research suggests that populations can diverge despite exchanging genes. Here I use a common garden experiment to assess the combined effects of gene flow and natural selection on morphological variation of 16 wood frog (Rana sylvatica) populations, a species known to experience divergent selection pressures in open- and closed-canopy ponds across relatively small geographic scales. Wood frog tadpoles from different ponds showed significant morphological variation associated with canopy type with a trade-off between tail length and body depth consistent with previous research. In contrast, neutral genetic differentiation of nine microsatellite loci as measured by Jost's D was not associated with canopy type, indicating no pattern of isolation by environment. Genetic structure analyses indicated some substructure across the 16 ponds (K = 4); however, three out of four assigned clusters included both open- and closed-canopy ponds. Together, these results suggest that morphological divergence among these wood frog populations is occurring despite gene flow and that selection within these environments is strong. Furthermore, morphological variation among ponds differed across two sampling periods during larval development, demonstrating the importance of evaluating phenotypic divergence over multiple time periods and at a time relevant to the processes being studied.}, } @article {pmid29531670, year = {2018}, author = {Brown, MBGJ and Gemmill, CEC and Miller, S and Wehi, PM}, title = {Diet selectivity in a terrestrial forest invertebrate, the Auckland tree wētā, across three habitat zones.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2495-2503}, pmid = {29531670}, issn = {2045-7758}, abstract = {Insects are important but overlooked components of forest ecosystems in New Zealand. For many insect species, information on foraging patterns and trophic relationships is lacking. We examined diet composition and selectivity in a large-bodied insect, the Auckland tree wētā Hemideina thoracica, in three habitat zones in a lowland New Zealand forest. We asked whether H. thoracica selectively forage from available plant food sources, and whether these choices were lipid-rich compared to nonpreferred available plants. We also identified the proportion of invertebrates in their frass as a proxy for omnivory. From reconnaissance plot sampling, together with fecal fragment analysis, we report that more than 93% of individual tree wētā had eaten invertebrates before capture. Additionally, wētā in the highest elevation hillslope habitat zone consumed significantly fewer species of plants on average than wētā on the low-elevation terrace habitat. Upper hillslope wētā also had the highest average number of invertebrate fragments in their frass, significantly more than wētā in the low-elevation terrace habitat zone. Wētā showed high variability in the consumption of fruit and seeds across all habitat zones. Generally, we did not observe diet differences between the sexes (although it appears that male wētā in the mid-hillslope habitat ate fruits and seeds more voraciously than females), suggesting that the sexes have similar niche breadths and display similar degrees of omnivorous behavior. Extraction of leaf lipids demonstrated a range of lipid content values in available plants, and Ivlev's Electivity Index indicated that plant species which demonstrated high electivity tended to have higher concentrations of lipids in their leaves. Our findings indicate that H. thoracica forage omnivorously and selectively, and hence play multiple roles in native ecosystems and food webs.}, } @article {pmid29531669, year = {2018}, author = {Ellis, S and Franks, DW and Nattrass, S and Cant, MA and Bradley, DL and Giles, D and Balcomb, KC and Croft, DP}, title = {Postreproductive lifespans are rare in mammals.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2482-2494}, pmid = {29531669}, issn = {2045-7758}, abstract = {A species has a post-reproductive stage if, like humans, a female entering the adult population can expect to live a substantial proportion of their life after their last reproductive event. However, it is conceptually and statistically challenging to distinguish these true post-reproductive stages from the usual processes of senescence, which can result in females occasionally surviving past their last reproductive event. Hence, despite considerable interest, the taxonomic prevalence of post-reproductive stages remains unclear and debated. In this study we use life tables constructed from published data on wild populations of mammals, and statistical measures of post-reproductive lifespans, to distinguish true post-reproductive stages from artefacts of senescence and demography in 52 species. We find post-reproductive stages are rare in mammals and are limited to humans and a few species of toothed whales. By resolving this long-standing debate, we hope to provide clarity for researchers in the field of evolutionary biology and a solid foundation for further studies investigating the evolution and adaptive significance of this unusual life history trait.}, } @article {pmid29531668, year = {2018}, author = {Street, GM and Erovenko, IV and Rowell, JT}, title = {Dynamical facilitation of the ideal free distribution in nonideal populations.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2471-2481}, pmid = {29531668}, issn = {2045-7758}, abstract = {The ideal free distribution (IFD) requires that individuals can accurately perceive density-dependent habitat quality, while failure to discern quality differences below a given perception threshold results in distributions approaching spatial uniformity. Here, we investigate the role of population growth in restoring a nonideal population to the IFD. We place a simple model of discrete patch choice under limits to the resolution by which patch quality is perceived and include population growth driven by that underlying quality. Our model follows the population's distribution through both breeding and dispersal seasons when perception limits differ in their likely influence. We demonstrate that populations of perception limited movers can approximate an IFD provided sufficient population growth; however, the emergent IFD would be temporally inconstant and correspond to reproductive events. The time to emergence of the IFD during breeding is shorter under exponential growth than under logistic growth. The IFD during early colonization of a community persists longer when more patches are available to individuals. As the population matures and dispersal becomes increasingly random, there is an oscillation in the observance of IFD, with peaks most closely approximating the IFD occurring immediately after reproductive events, and higher reproductive rates producing distributions closer to the IFD.}, } @article {pmid29531667, year = {2018}, author = {Janišová, M and Skokanová, K and Hlásny, T}, title = {Ecological differentiation, speciation, and rarity: How do they match in Tephroseris longifolia agg. (Asteraceae)?.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2453-2470}, pmid = {29531667}, issn = {2045-7758}, abstract = {Tephroseris longifolia agg. is a complex group of outcrossing perennials distributed throughout Central Europe. Recent morphological study revealed six morphotypes corresponding to five previously distinguished subspecies, together with Alpine and Pannonian morphotypes of T. longifolia subsp. longifolia. The delimited morphotypes differ in relative DNA content, geographical range, and rarity. We compared ecological niches of the six morphotypes in order to assess the impact of ecological differentiation on the speciation processes within the T. longifolia agg. Further, we examined whether morphotypes with small range are more ecologically specialized than their widespread relatives. The distribution area of the aggregate includes the Alps, Apennines, Carpathians, and the Pannonian Basin. Ecological variables linked to climate, topography, soil, and vegetation were gathered from 135 circular plots recorded in 35 localities. Related variables were grouped to describe the partial ecological niches: climatic, topographic, pedological, biotic, and coenotic (based either on vascular plants or on bryophytes), each of them visualized as an envelope in the two-dimensional nonmetric multidimensional scaling ordination space. Each partial ecological niche for a given morphotype was characterized by its position (location of the envelope centroid), breadth (surface of the envelope), and overlaps with envelopes of the other morphotypes. Mantel statistics based on Spearman correlation coefficients were used to quantify differentiation of morphotypes in ecological parameters represented by the partial ecological niches. The significant niche differentiation was confirmed for climatic, topographic, pedological, and vascular plant-based coenotic niches. Ecological niche differentiation corresponded well to morphological and partially also to karyological differentiation. Narrowly distributed morphotypes occupied more specific habitats and had narrower ecological niches than their widespread relatives. Ecological differentiation could be considered an important driver in allopatric speciation within the T. longifolia agg. Our results demonstrate that quantification of ecological divergence is helpful in assessing evolutionary history of closely related taxa.}, } @article {pmid29531666, year = {2018}, author = {Guo, WY and Lambertini, C and Pyšek, P and Meyerson, LA and Brix, H}, title = {Living in two worlds: Evolutionary mechanisms act differently in the native and introduced ranges of an invasive plant.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2440-2452}, pmid = {29531666}, issn = {2045-7758}, abstract = {Identifying the factors that influence spatial genetic structure among populations can provide insights into the evolution of invasive plants. In this study, we used the common reed (Phragmites australis), a grass native in Europe and invading North America, to examine the relative importance of geographic, environmental (represented by climate here), and human effects on population genetic structure and its changes during invasion. We collected samples of P. australis from both the invaded North American and native European ranges and used molecular markers to investigate the population genetic structure within and between ranges. We used path analysis to identify the contributions of each of the three factors-geographic, environmental, and human-related-to the formation of spatial genetic patterns. Genetic differentiation was observed between the introduced and native populations, and their genetic structure in the native and introduced ranges was different. There were strong effects of geography and environment on the genetic structure of populations in the native range, but the human-related factors manifested through colonization of anthropogenic habitats in the introduced range counteracted the effects of environment. The between-range genetic differences among populations were mainly explained by the heterogeneous environment between the ranges, with the coefficient 2.6 times higher for the environment than that explained by the geographic distance. Human activities were the primary contributor to the genetic structure of the introduced populations. The significant environmental divergence between ranges and the strong contribution of human activities to the genetic structure in the introduced range suggest that invasive populations of P. australis have evolved to adapt to a different climate and to human-made habitats in North America.}, } @article {pmid29531665, year = {2018}, author = {Gerken, AR and Campbell, JF}, title = {Life history changes in Trogoderma variabile and T. inclusum due to mating delay with implications for mating disruption as a management tactic.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2428-2439}, pmid = {29531665}, issn = {2045-7758}, abstract = {Controlling postharvest pest species is a costly process with insecticide resistance and species-specific control requiring multiple tactics. Mating disruption (MD) can be used to both decrease a female's access to males and delay timing of mating and decreases overall mating success in a population and population growth rate. Development of new commercially available MD products requires an understanding of life history parameters associated with mating delay. These can provide information for targeting proportions of reproducing individuals using MD. After delaying mating for females of two closely related beetle species, Trogoderma variabile and T. inclusum, we surveyed survivorship, number of eggs laid, and number of progeny emerged. With increases in mating age, total number of eggs laid and total number of progeny emerged significantly declined over time. T. inclusum typically had greater numbers of eggs laid and progeny emerged compared to T. variabile as female age at mating increased, suggesting that T. inclusum may be more resistant to long-term delays in mating. Life span showed an increase as mating age increased but life span significantly decreased almost immediately following mating. Simulations depicting multiple distributions of mating within a population suggest that in a closed population, high levels of mating delay significantly reduced reproductive growth rates. Although reproductive growth rates were decreased with increased mating age, they are still large enough to maintain populations. This study highlights the differences in life history between two closely related species, suggesting that T. inclusum outperforms T. variabile over the course of a life span, but T. variabile has better reproductive capabilities early in life. MD may also be a viable component of a pest management system for these two species as it significantly decreased overall reproductive output and population growth.}, } @article {pmid29531664, year = {2018}, author = {Hou, R and Ouyang, Z and Han, D and Wilson, GV}, title = {Effects of field experimental warming on wheat root distribution under conventional tillage and no-tillage systems.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2418-2427}, pmid = {29531664}, issn = {2045-7758}, abstract = {Despite the obvious importance of roots to agro-ecosystem functioning, few studies have attempted to examine the effects of warming on root biomass and distribution, especially under different tillage systems. In this study, we performed a field warming experiment using infrared heaters on winter wheat, in long-term conventional tillage and no-tillage plots, to determine the responses of root biomass and distribution to warming. Soil monoliths were collected from three soil depths (0-10, 10-20, and 20-30 cm). Results showed that root biomass was noticeably increased under both till and no-till tillage systems (12.1% and 12.9% in 2011, and 9.9% and 14.5% in 2013, in the two tillage systems, respectively) in the 0-30 cm depth, associated with a similar increase in shoot biomass. However, warming-induced root biomass increases occurred in the deeper soil layers (i.e., 10-20 and 20-30 cm) in till, while the increase in no-till was focused in the surface layer (0-10 cm). Differences in the warming-induced increases in root biomass between till and no-till were positively correlated with the differences in soil total nitrogen (R2 = .863, p < .001) and soil bulk density (R2 = .853, p < .001). Knowledge of the distribution of wheat root in response to warming should help manage nutrient application and cycling of soil C-N pools under anticipated climate change conditions.}, } @article {pmid29531663, year = {2018}, author = {Miyazawa, H and Nakano, H}, title = {Multiple surveys employing a new sample-processing protocol reveal the genetic diversity of placozoans in Japan.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2407-2417}, pmid = {29531663}, issn = {2045-7758}, abstract = {Placozoans, flat free-living marine invertebrates, possess an extremely simple bauplan lacking neurons and muscle cells and represent one of the earliest-branching metazoan phyla. They are widely distributed from temperate to tropical oceans. Based on mitochondrial 16S rRNA sequences, 19 haplotypes forming seven distinct clades have been reported in placozoans to date. In Japan, placozoans have been found at nine locations, but 16S genotyping has been performed at only two of these locations. Here, we propose a new processing protocol, "ethanol-treated substrate sampling," for collecting placozoans from natural environments. We also report the collection of placozoans from three new locations, the islands of Shikine-jima, Chichi-jima, and Haha-jima, and we present the distribution of the 16S haplotypes of placozoans in Japan. Multiple surveys conducted at multiple locations yielded five haplotypes that were not reported previously, revealing high genetic diversity in Japan, especially at Shimoda and Shikine-jima Island. The observed geographic distribution patterns were different among haplotypes; some were widely distributed, while others were sampled only from a single location. However, samplings conducted on different dates at the same sites yielded different haplotypes, suggesting that placozoans of a given haplotype do not inhabit the same site constantly throughout the year. Continued sampling efforts conducted during all seasons at multiple locations worldwide and the development of molecular markers within the haplotypes are needed to reveal the geographic distribution pattern and dispersal history of placozoans in greater detail.}, } @article {pmid29531662, year = {2018}, author = {Hao, M and Zhang, C and Zhao, X and von Gadow, K}, title = {Functional and phylogenetic diversity determine woody productivity in a temperate forest.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2395-2406}, pmid = {29531662}, issn = {2045-7758}, abstract = {Understanding the relationships between biodiversity and ecosystem productivity has become a central issue in ecology and conservation biology studies, particularly when these relationships are connected with global climate change and species extinction. However, which facets of biodiversity (i.e. taxonomic, functional, and phylogenetic diversity) account most for variations in productivity are still not understood very well. This is especially true with regard to temperate forest ecosystems. In this study, we used a dataset from a stem-mapped permanent forest plot in northeastern China exploring the relationships between biodiversity and productivity at different spatial scales (20 × 20 m; 40 × 40 m; and 60 × 60 m). The influence of specific environmental conditions (topographic conditions) and stand maturity (expressed by initial stand volume and biomass) were taken into account using the multivariate approach known as structural equation models. The variable "Biodiversity" includes taxonomic (Shannon), functional (FDis), and phylogenetic diversity (PD). Biodiversity-productivity relationships varied with the spatial scales. At the scale of 20 × 20 m, PD and FDis significantly affected forest biomass productivity, while Shannon had only indirect effects. At the 40 × 40 m and 60 × 60 m scales, biodiversity and productivity were weakly correlated. The initial stand volume and biomass were the most important drivers of forest productivity. The local environmental conditions significantly influenced the stand volume, biomass, biodiversity, and productivity. The results highlight the scale dependency of the relationships between forest biodiversity and productivity. The positive role of biodiversity in facilitating forest productivity was confirmed at the smaller scales. Our findings emphasize the fundamental role of environmental conditions in determining forest ecosystem performances. The results of this study provide a better understanding of the underlying ecological processes that influence specific forest biodiversity and productivity relationships.}, } @article {pmid29531661, year = {2018}, author = {Burley, NT and Hamedani, E and Symanski, C}, title = {Mate choice decision rules: Trait synergisms and preference shifts.}, journal = {Ecology and evolution}, volume = {8}, number = {5}, pages = {2380-2394}, pmid = {29531661}, issn = {2045-7758}, abstract = {An important and understudied question in sexual selection is how females evaluate information from multiple secondary sexual traits (SSTs), particularly when expression of traits is phenotypically uncorrelated. We performed mate choice experiments on zebra finches (Taeniopygia guttata castanotis Gould) to evaluate two hypotheses: preference shifts (obstacles to choice using one trait increase chooser reliance on others) and trait synergisms (choice based on the sum/product of two or more independently varying traits). The first experiment, which employed males raised on diets that impact SST expression, supported the trait synergism hypothesis: overall, male pairing success was best predicted by synergisms involving beak color and cheek patch size. Results did not support the preference shift hypothesis. Results of a follow-up experiment that included males reared on a single diet, and in which male beak color and cheek patch size were manipulated, were also consistent with the trait synergism hypothesis. Results have implications for understanding the long-term persistence of multiple SSTs in populations and for the measurement of repeatability and heritability of mate preferences.}, } @article {pmid29531367, year = {2018}, author = {Laber, CP and Hunter, JE and Carvalho, F and Collins, JR and Hunter, EJ and Schieler, BM and Boss, E and More, K and Frada, M and Thamatrakoln, K and Brown, CM and Haramaty, L and Ossolinski, J and Fredricks, H and Nissimov, JI and Vandzura, R and Sheyn, U and Lehahn, Y and Chant, RJ and Martins, AM and Coolen, MJL and Vardi, A and DiTullio, GR and Van Mooy, BAS and Bidle, KD}, title = {Coccolithovirus facilitation of carbon export in the North Atlantic.}, journal = {Nature microbiology}, volume = {3}, number = {5}, pages = {537-547}, doi = {10.1038/s41564-018-0128-4}, pmid = {29531367}, issn = {2058-5276}, abstract = {Marine phytoplankton account for approximately half of global primary productivity 1 , making their fate an important driver of the marine carbon cycle. Viruses are thought to recycle more than one-quarter of oceanic photosynthetically fixed organic carbon 2 , which can stimulate nutrient regeneration, primary production and upper ocean respiration 2 via lytic infection and the 'virus shunt'. Ultimately, this limits the trophic transfer of carbon and energy to both higher food webs and the deep ocean 2 . Using imagery taken by the Moderate Resolution Imaging Spectroradiometer (MODIS) onboard the Aqua satellite, along with a suite of diagnostic lipid- and gene-based molecular biomarkers, in situ optical sensors and sediment traps, we show that Coccolithovirus infections of mesoscale (~100 km) Emiliania huxleyi blooms in the North Atlantic are coupled with particle aggregation, high zooplankton grazing and greater downward vertical fluxes of both particulate organic and particulate inorganic carbon from the upper mixed layer. Our analyses captured blooms in different phases of infection (early, late and post) and revealed the highest export flux in 'early-infected blooms' with sinking particles being disproportionately enriched with infected cells and subsequently remineralized at depth in the mesopelagic. Our findings reveal viral infection as a previously unrecognized ecosystem process enhancing biological pump efficiency.}, } @article {pmid29531366, year = {2018}, author = {Garza, DR and van Verk, MC and Huynen, MA and Dutilh, BE}, title = {Towards predicting the environmental metabolome from metagenomics with a mechanistic model.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {456-460}, doi = {10.1038/s41564-018-0124-8}, pmid = {29531366}, issn = {2058-5276}, abstract = {The environmental metabolome and metabolic potential of microorganisms are dominant and essential factors shaping microbial community composition. Recent advances in genome annotation and systems biology now allow us to semiautomatically reconstruct genome-scale metabolic models (GSMMs) of microorganisms based on their genome sequence 1 . Next, growth of these models in a defined metabolic environment can be predicted in silico, mechanistically linking the metabolic fluxes of individual microbial populations to the community dynamics. A major advantage of GSMMs is that no training data is needed, besides information about the metabolic capacity of individual genes (genome annotation) and knowledge of the available environmental metabolites that allow the microorganism to grow. However, the composition of the environment is often not fully determined and remains difficult to measure 2 . We hypothesized that the relative abundance of different bacterial species, as measured by metagenomics, can be combined with GSMMs of individual bacteria to reveal the metabolic status of a given biome. Using a newly developed algorithm involving over 1,500 GSMMs of human-associated bacteria, we inferred distinct metabolomes for four human body sites that are consistent with experimental data. Together, we link the metagenome to the metabolome in a mechanistic framework towards predictive microbiome modelling.}, } @article {pmid29531365, year = {2018}, author = {Knowlton, JJ and Fernández de Castro, I and Ashbrook, AW and Gestaut, DR and Zamora, PF and Bauer, JA and Forrest, JC and Frydman, J and Risco, C and Dermody, TS}, title = {The TRiC chaperonin controls reovirus replication through outer-capsid folding.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {481-493}, pmid = {29531365}, issn = {2058-5276}, support = {UL1 TR000445/TR/NCATS NIH HHS/United States ; R01 AI032539/AI/NIAID NIH HHS/United States ; R01 AI127447/AI/NIAID NIH HHS/United States ; F30 AI122563/AI/NIAID NIH HHS/United States ; T32 GM007347/GM/NIGMS NIH HHS/United States ; R01 GM074074/GM/NIGMS NIH HHS/United States ; UL1 TR002243/TR/NCATS NIH HHS/United States ; }, abstract = {Viruses are molecular machines sustained through a life cycle that requires replication within host cells. Throughout the infectious cycle, viral and cellular components interact to advance the multistep process required to produce progeny virions. Despite progress made in understanding the virus-host protein interactome, much remains to be discovered about the cellular factors that function during infection, especially those operating at terminal steps in replication. In an RNA interference screen, we identified the eukaryotic chaperonin T-complex protein-1 (TCP-1) ring complex (TRiC; also called CCT for chaperonin containing TCP-1) as a cellular factor required for late events in the replication of mammalian reovirus. We discovered that TRiC functions in reovirus replication through a mechanism that involves folding the viral σ3 major outer-capsid protein into a form capable of assembling onto virus particles. TRiC also complexes with homologous capsid proteins of closely related viruses. Our data define a critical function for TRiC in the viral assembly process and raise the possibility that this mechanism is conserved in related non-enveloped viruses. These results also provide insight into TRiC protein substrates and establish a rationale for the development of small-molecule inhibitors of TRiC as potential antiviral therapeutics.}, } @article {pmid29531354, year = {2018}, author = {Malik, R and Chauhan, G and Traylor, M and Sargurupremraj, M and Okada, Y and Mishra, A and Rutten-Jacobs, L and Giese, AK and van der Laan, SW and Gretarsdottir, S and Anderson, CD and Chong, M and Adams, HHH and Ago, T and Almgren, P and Amouyel, P and Ay, H and Bartz, TM and Benavente, OR and Bevan, S and Boncoraglio, GB and Brown, RD and Butterworth, AS and Carrera, C and Carty, CL and Chasman, DI and Chen, WM and Cole, JW and Correa, A and Cotlarciuc, I and Cruchaga, C and Danesh, J and de Bakker, PIW and DeStefano, AL and den Hoed, M and Duan, Q and Engelter, ST and Falcone, GJ and Gottesman, RF and Grewal, RP and Gudnason, V and Gustafsson, S and Haessler, J and Harris, TB and Hassan, A and Havulinna, AS and Heckbert, SR and Holliday, EG and Howard, G and Hsu, FC and Hyacinth, HI and Ikram, MA and Ingelsson, E and Irvin, MR and Jian, X and Jiménez-Conde, J and Johnson, JA and Jukema, JW and Kanai, M and Keene, KL and Kissela, BM and Kleindorfer, DO and Kooperberg, C and Kubo, M and Lange, LA and Langefeld, CD and Langenberg, C and Launer, LJ and Lee, JM and Lemmens, R and Leys, D and Lewis, CM and Lin, WY and Lindgren, AG and Lorentzen, E and Magnusson, PK and Maguire, J and Manichaikul, A and McArdle, PF and Meschia, JF and Mitchell, BD and Mosley, TH and Nalls, MA and Ninomiya, T and O'Donnell, MJ and Psaty, BM and Pulit, SL and Rannikmäe, K and Reiner, AP and Rexrode, KM and Rice, K and Rich, SS and Ridker, PM and Rost, NS and Rothwell, PM and Rotter, JI and Rundek, T and Sacco, RL and Sakaue, S and Sale, MM and Salomaa, V and Sapkota, BR and Schmidt, R and Schmidt, CO and Schminke, U and Sharma, P and Slowik, A and Sudlow, CLM and Tanislav, C and Tatlisumak, T and Taylor, KD and Thijs, VNS and Thorleifsson, G and Thorsteinsdottir, U and Tiedt, S and Trompet, S and Tzourio, C and van Duijn, CM and Walters, M and Wareham, NJ and Wassertheil-Smoller, S and Wilson, JG and Wiggins, KL and Yang, Q and Yusuf, S and Bis, JC and Pastinen, T and Ruusalepp, A and Schadt, EE and Koplev, S and Björkegren, JLM and Codoni, V and Civelek, M and Smith, NL and Trégouët, DA and Christophersen, IE and Roselli, C and Lubitz, SA and Ellinor, PT and Tai, ES and Kooner, JS and Kato, N and He, J and van der Harst, P and Elliott, P and Chambers, JC and Takeuchi, F and Johnson, AD and Sanghera, DK and Melander, O and Jern, C and Strbian, D and Fernandez-Cadenas, I and Longstreth, WT and Rolfs, A and Hata, J and Woo, D and Rosand, J and Pare, G and Hopewell, JC and Saleheen, D and Stefansson, K and Worrall, BB and Kittner, SJ and Seshadri, S and Fornage, M and Markus, HS and Howson, JMM and Kamatani, Y and Debette, S and Dichgans, M and Malik, R and Chauhan, G and Traylor, M and Sargurupremraj, M and Okada, Y and Mishra, A and Rutten-Jacobs, L and Giese, AK and van der Laan, SW and Gretarsdottir, S and Anderson, CD and Chong, M and Adams, HHH and Ago, T and Almgren, P and Amouyel, P and Ay, H and Bartz, TM and Benavente, OR and Bevan, S and Boncoraglio, GB and Brown, RD and Butterworth, AS and Carrera, C and Carty, CL and Chasman, DI and Chen, WM and Cole, JW and Correa, A and Cotlarciuc, I and Cruchaga, C and Danesh, J and de Bakker, PIW and DeStefano, AL and Hoed, MD and Duan, Q and Engelter, ST and Falcone, GJ and Gottesman, RF and Grewal, RP and Gudnason, V and Gustafsson, S and Haessler, J and Harris, TB and Hassan, A and Havulinna, AS and Heckbert, SR and Holliday, EG and Howard, G and Hsu, FC and Hyacinth, HI and Ikram, MA and Ingelsson, E and Irvin, MR and Jian, X and Jiménez-Conde, J and Johnson, JA and Jukema, JW and Kanai, M and Keene, KL and Kissela, BM and Kleindorfer, DO and Kooperberg, C and Kubo, M and Lange, LA and Langefeld, CD and Langenberg, C and Launer, LJ and Lee, JM and Lemmens, R and Leys, D and Lewis, CM and Lin, WY and Lindgren, AG and Lorentzen, E and Magnusson, PK and Maguire, J and Manichaikul, A and McArdle, PF and Meschia, JF and Mitchell, BD and Mosley, TH and Nalls, MA and Ninomiya, T and O'Donnell, MJ and Psaty, BM and Pulit, SL and Rannikmäe, K and Reiner, AP and Rexrode, KM and Rice, K and Rich, SS and Ridker, PM and Rost, NS and Rothwell, PM and Rotter, JI and Rundek, T and Sacco, RL and Sakaue, S and Sale, MM and Salomaa, V and Sapkota, BR and Schmidt, R and Schmidt, CO and Schminke, U and Sharma, P and Slowik, A and Sudlow, CLM and Tanislav, C and Tatlisumak, T and Taylor, KD and Thijs, VNS and Thorleifsson, G and Thorsteinsdottir, U and Tiedt, S and Trompet, S and Tzourio, C and van Duijn, CM and Walters, M and Wareham, NJ and Wassertheil-Smoller, S and Wilson, JG and Wiggins, KL and Yang, Q and Yusuf, S and Amin, N and Aparicio, HS and Arnett, DK and Attia, J and Beiser, AS and Berr, C and Buring, JE and Bustamante, M and Caso, V and Cheng, YC and Choi, SH and Chowhan, A and Cullell, N and Dartigues, JF and Delavaran, H and Delgado, P and Dörr, M and Engström, G and Ford, I and Gurpreet, WS and Hamsten, A and Heitsch, L and Hozawa, A and Ibanez, L and Ilinca, A and Ingelsson, M and Iwasaki, M and Jackson, RD and Jood, K and Jousilahti, P and Kaffashian, S and Kalra, L and Kamouchi, M and Kitazono, T and Kjartansson, O and Kloss, M and Koudstaal, PJ and Krupinski, J and Labovitz, DL and Laurie, CC and Levi, CR and Li, L and Lind, L and Lindgren, CM and Lioutas, V and Liu, YM and Lopez, OL and Makoto, H and Martinez-Majander, N and Matsuda, K and Minegishi, N and Montaner, J and Morris, AP and Muiño, E and Müller-Nurasyid, M and Norrving, B and Ogishima, S and Parati, EA and Peddareddygari, LR and Pedersen, NL and Pera, J and Perola, M and Pezzini, A and Pileggi, S and Rabionet, R and Riba-Llena, I and Ribasés, M and Romero, JR and Roquer, J and Rudd, AG and Sarin, AP and Sarju, R and Sarnowski, C and Sasaki, M and Satizabal, CL and Satoh, M and Sattar, N and Sawada, N and Sibolt, G and Sigurdsson, Á and Smith, A and Sobue, K and Soriano-Tárraga, C and Stanne, T and Stine, OC and Stott, DJ and Strauch, K and Takai, T and Tanaka, H and Tanno, K and Teumer, A and Tomppo, L and Torres-Aguila, NP and Touze, E and Tsugane, S and Uitterlinden, AG and Valdimarsson, EM and van der Lee, SJ and Völzke, H and Wakai, K and Weir, D and Williams, SR and Wolfe, CDA and Wong, Q and Xu, H and Yamaji, T and Sanghera, DK and Melander, O and Jern, C and Strbian, D and Fernandez-Cadenas, I and Longstreth, WT and Rolfs, A and Hata, J and Woo, D and Rosand, J and Pare, G and Hopewell, JC and Saleheen, D and Stefansson, K and Worrall, BB and Kittner, SJ and Seshadri, S and Fornage, M and Markus, HS and Howson, JMM and Kamatani, Y and Debette, S and Dichgans, M and , and , and , and , and , and , and , and , and , and , and , and , and , and , and , and , }, title = {Multiancestry genome-wide association study of 520,000 subjects identifies 32 loci associated with stroke and stroke subtypes.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {524-537}, pmid = {29531354}, issn = {1546-1718}, support = {R01 NS017950/NS/NINDS NIH HHS/United States ; MR/L003120/1//Medical Research Council/United Kingdom ; MC_UU_12015/1//Medical Research Council/United Kingdom ; P30 DK063491/DK/NIDDK NIH HHS/United States ; R01 HL138423/HL/NHLBI NIH HHS/United States ; FS/14/55/30806//British Heart Foundation/United Kingdom ; R01 HL088521/HL/NHLBI NIH HHS/United States ; Z99 AG999999/NULL/Intramural NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; K23 HL114724/HL/NHLBI NIH HHS/United States ; }, abstract = {Stroke has multiple etiologies, but the underlying genes and pathways are largely unknown. We conducted a multiancestry genome-wide-association meta-analysis in 521,612 individuals (67,162 cases and 454,450 controls) and discovered 22 new stroke risk loci, bringing the total to 32. We further found shared genetic variation with related vascular traits, including blood pressure, cardiac traits, and venous thromboembolism, at individual loci (n = 18), and using genetic risk scores and linkage-disequilibrium-score regression. Several loci exhibited distinct association and pleiotropy patterns for etiological stroke subtypes. Eleven new susceptibility loci indicate mechanisms not previously implicated in stroke pathophysiology, with prioritization of risk variants and genes accomplished through bioinformatics analyses using extensive functional datasets. Stroke risk loci were significantly enriched in drug targets for antithrombotic therapy.}, } @article {pmid29531347, year = {2018}, author = {Bouckaert, RR and Bowern, C and Atkinson, QD}, title = {The origin and expansion of Pama-Nyungan languages across Australia.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {741-749}, doi = {10.1038/s41559-018-0489-3}, pmid = {29531347}, issn = {2397-334X}, abstract = {It remains a mystery how Pama-Nyungan, the world's largest hunter-gatherer language family, came to dominate the Australian continent. Some argue that social or technological advantages allowed rapid language replacement from the Gulf Plains region during the mid-Holocene. Others have proposed expansions from refugia linked to climatic changes after the last ice age or, more controversially, during the initial colonization of Australia. Here, we combine basic vocabulary data from 306 Pama-Nyungan languages with Bayesian phylogeographic methods to explicitly model the expansion of the family across Australia and test between these origin scenarios. We find strong and robust support for a Pama-Nyungan origin in the Gulf Plains region during the mid-Holocene, implying rapid replacement of non-Pama-Nyungan languages. Concomitant changes in the archaeological record, together with a lack of strong genetic evidence for Holocene population expansion, suggests that Pama-Nyungan languages were carried as part of an expanding package of cultural innovations that probably facilitated the absorption and assimilation of existing hunter-gatherer groups.}, } @article {pmid29531346, year = {2018}, author = {Alfaro, ME and Faircloth, BC and Harrington, RC and Sorenson, L and Friedman, M and Thacker, CE and Oliveros, CH and Černý, D and Near, TJ}, title = {Explosive diversification of marine fishes at the Cretaceous-Palaeogene boundary.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {688-696}, doi = {10.1038/s41559-018-0494-6}, pmid = {29531346}, issn = {2397-334X}, abstract = {The Cretaceous-Palaeogene (K-Pg) mass extinction is linked to the rapid emergence of ecologically divergent higher taxa (for example, families and orders) across terrestrial vertebrates, but its impact on the diversification of marine vertebrates is less clear. Spiny-rayed fishes (Acanthomorpha) provide an ideal system for exploring the effects of the K-Pg on fish diversification, yet despite decades of morphological and molecular phylogenetic efforts, resolution of both early diverging lineages and enormously diverse subclades remains problematic. Recent multilocus studies have provided the first resolved phylogenetic backbone for acanthomorphs and suggested novel relationships among major lineages. However, these new relationships and associated timescales have not been interrogated using phylogenomic approaches. Here, we use targeted enrichment of >1,000 ultraconserved elements in conjunction with a divergence time analysis to resolve relationships among 120 major acanthomorph lineages and provide a new timescale for acanthomorph radiation. Our results include a well-supported topology that strongly resolves relationships along the acanthomorph backbone and the recovery of several new relationships within six major percomorph subclades. Divergence time analyses also reveal that crown ages for five of these subclades, and for the bulk of the species diversity in the sixth, coincide with the K-Pg boundary, with divergences between anatomically and ecologically distinctive suprafamilial clades concentrated in the first 10 million years of the Cenozoic.}, } @article {pmid29531345, year = {2018}, author = {Lopez, M and Kousathanas, A and Quach, H and Harmant, C and Mouguiama-Daouda, P and Hombert, JM and Froment, A and Perry, GH and Barreiro, LB and Verdu, P and Patin, E and Quintana-Murci, L}, title = {The demographic history and mutational load of African hunter-gatherers and farmers.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {721-730}, doi = {10.1038/s41559-018-0496-4}, pmid = {29531345}, issn = {2397-334X}, abstract = {Understanding how deleterious genetic variation is distributed across human populations is of key importance in evolutionary biology and medical genetics. However, the impact of population size changes and gene flow on the corresponding mutational load remains a controversial topic. Here, we report high-coverage exomes from 300 rainforest hunter-gatherers and farmers of central Africa, whose distinct subsistence strategies are expected to have impacted their demographic pasts. Detailed demographic inference indicates that hunter-gatherers and farmers recently experienced population collapses and expansions, respectively, accompanied by increased gene flow. We show that the distribution of deleterious alleles across these populations is compatible with a similar efficacy of selection to remove deleterious variants with additive effects, and predict with simulations that their present-day additive mutation load is almost identical. For recessive mutations, although an increased load is predicted for hunter-gatherers, this increase has probably been partially counteracted by strong gene flow from expanding farmers. Collectively, our predicted and empirical observations suggest that the impact of the recent population decline of African hunter-gatherers on their mutation load has been modest and more restrained than would be expected under a fully recessive model of dominance.}, } @article {pmid29531344, year = {2018}, author = {Singh, GG}, title = {Addressing discrimination and diversity in ecology is not just about implicit bias.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {584}, doi = {10.1038/s41559-018-0516-4}, pmid = {29531344}, issn = {2397-334X}, } @article {pmid29531319, year = {2018}, author = {Beasley, MA and Trujillo, I and Leaman, R and Montes, M}, title = {A single population of red globular clusters around the massive compact galaxy NGC 1277.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {483-486}, pmid = {29531319}, issn = {1476-4687}, abstract = {Massive galaxies are thought to form in two phases: an initial collapse of gas and giant burst of central star formation, followed by the later accretion of material that builds up their stellar and dark-matter haloes. The systems of globular clusters within such galaxies are believed to form in a similar manner. The initial central burst forms metal-rich (spectrally red) clusters, whereas more metal-poor (spectrally blue) clusters are brought in by the later accretion of less-massive satellites. This formation process is thought to result in the multimodal optical colour distributions that are seen in the globular cluster systems of massive galaxies. Here we report optical observations of the massive relic-galaxy candidate NGC 1277-a nearby, un-evolved example of a high-redshift 'red nugget' galaxy. We find that the optical colour distribution of the cluster system of NGC 1277 is unimodal and entirely red. This finding is in strong contrast to other galaxies of similar and larger stellar mass, the cluster systems of which always exhibit (and are generally dominated by) blue clusters. We argue that the colour distribution of the cluster system of NGC 1277 indicates that the galaxy has undergone little (if any) mass accretion after its initial collapse, and use simulations of possible merger histories to show that the stellar mass due to accretion is probably at most ten per cent of the total stellar mass of the galaxy. These results confirm that NGC 1277 is a genuine relic galaxy and demonstrate that blue clusters constitute an accreted population in present-day massive galaxies.}, } @article {pmid29531318, year = {2018}, author = {Smith, EI and Jacobs, Z and Johnsen, R and Ren, M and Fisher, EC and Oestmo, S and Wilkins, J and Harris, JA and Karkanas, P and Fitch, S and Ciravolo, A and Keenan, D and Cleghorn, N and Lane, CS and Matthews, T and Marean, CW}, title = {Humans thrived in South Africa through the Toba eruption about 74,000 years ago.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {511-515}, pmid = {29531318}, issn = {1476-4687}, mesh = {*Adaptation, Psychological ; Archaeology ; Geologic Sediments/chemistry ; Glass/analysis/chemistry ; History, Ancient ; Humans ; Indonesia ; Industrial Development/*history ; South Africa ; Spatio-Temporal Analysis ; Volcanic Eruptions/*history ; }, abstract = {Approximately 74 thousand years ago (ka), the Toba caldera erupted in Sumatra. Since the magnitude of this eruption was first established, its effects on climate, environment and humans have been debated. Here we describe the discovery of microscopic glass shards characteristic of the Youngest Toba Tuff-ashfall from the Toba eruption-in two archaeological sites on the south coast of South Africa, a region in which there is evidence for early human behavioural complexity. An independently derived dating model supports a date of approximately 74 ka for the sediments containing the Youngest Toba Tuff glass shards. By defining the input of shards at both sites, which are located nine kilometres apart, we are able to establish a close temporal correlation between them. Our high-resolution excavation and sampling technique enable exact comparisons between the input of Youngest Toba Tuff glass shards and the evidence for human occupation. Humans in this region thrived through the Toba event and the ensuing full glacial conditions, perhaps as a combined result of the uniquely rich resource base of the region and fully evolved modern human adaptation.}, } @article {pmid29531154, year = {2018}, author = {Altizer, S and Becker, DJ and Epstein, JH and Forbes, KM and Gillespie, TR and Hall, RJ and Hawley, DM and Hernandez, SM and Martin, LB and Plowright, RK and Satterfield, DA and Streicker, DG}, title = {Food for contagion: synthesis and future directions for studying host-parasite responses to resource shifts in anthropogenic environments.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531154}, issn = {1471-2970}, support = {102507//Wellcome Trust/United Kingdom ; P20 GM103474/GM/NIGMS NIH HHS/United States ; P30 GM110732/GM/NIGMS NIH HHS/United States ; }, mesh = {Animal Feed/supply & distribution ; Animals ; Animals, Wild/*immunology/microbiology/parasitology/virology ; Behavior, Animal/physiology ; Communicable Diseases/epidemiology/immunology/transmission/*veterinary ; Conservation of Natural Resources/methods ; Epidemiological Monitoring ; *Host-Parasite Interactions ; *Host-Pathogen Interactions ; Humans ; Immunity, Innate ; Population Dynamics/statistics & numerical data ; Risk Factors ; }, abstract = {Human-provided resource subsidies for wildlife are diverse, common and have profound consequences for wildlife-pathogen interactions, as demonstrated by papers in this themed issue spanning empirical, theoretical and management perspectives from a range of study systems. Contributions cut across scales of organization, from the within-host dynamics of immune function, to population-level impacts on parasite transmission, to landscape- and regional-scale patterns of infection. In this concluding paper, we identify common threads and key findings from author contributions, including the consequences of resource subsidies for (i) host immunity; (ii) animal aggregation and contact rates; (iii) host movement and landscape-level infection patterns; and (iv) interspecific contacts and cross-species transmission. Exciting avenues for future work include studies that integrate mechanistic modelling and empirical approaches to better explore cross-scale processes, and experimental manipulations of food resources to quantify host and pathogen responses. Work is also needed to examine evolutionary responses to provisioning, and ask how diet-altered changes to the host microbiome influence infection processes. Given the massive public health and conservation implications of anthropogenic resource shifts, we end by underscoring the need for practical recommendations to manage supplemental feeding practices, limit human-wildlife conflicts over shared food resources and reduce cross-species transmission risks, including to humans.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531153, year = {2018}, author = {Civitello, DJ and Allman, BE and Morozumi, C and Rohr, JR}, title = {Assessing the direct and indirect effects of food provisioning and nutrient enrichment on wildlife infectious disease dynamics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531153}, issn = {1471-2970}, mesh = {Animals ; Chlorophyta/microbiology ; Competitive Behavior/physiology ; Daphnia/*microbiology ; Fish Diseases/*epidemiology/microbiology/transmission ; Fishes/microbiology/physiology ; Food Chain ; *Host-Pathogen Interactions ; Humans ; Metschnikowia/growth & development/pathogenicity ; *Models, Statistical ; Mycoses/epidemiology/microbiology/transmission/*veterinary ; Predatory Behavior/physiology ; Spores, Fungal/growth & development/pathogenicity ; }, abstract = {Anthropogenic resource supplementation can shape wildlife disease directly by altering the traits and densities of hosts and parasites or indirectly by stimulating prey, competitor or predator species. We first assess the direct epidemiological consequences of supplementation, highlighting the similarities and differences between food provisioning and two widespread forms of nutrient input: agricultural fertilization and aquatic nutrient enrichment. We then review an aquatic disease system and a general model to assess whether predator and competitor species can enhance or overturn the direct effects of enrichment. All forms of supplementation can directly affect epidemics by increasing host population size or altering parasite production within hosts, but food provisioning is most likely to aggregate hosts and increase parasite transmission. However, if predators or competitors increase in response to supplementation, they could alter resource-fuelled outbreaks in focal hosts. We recommend identifying the traits of hosts, parasites or interacting species that best predict epidemiological responses to supplementation and evaluating the relative importance of these direct and indirect mechanisms. Theory and experiments should examine the timing of behavioural, physiological and demographic changes for realistic, variable scenarios of supplementation. A more integrative view of resource supplementation and wildlife disease could yield broadly applicable disease management strategies.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531152, year = {2018}, author = {Murray, MH and Kidd, AD and Curry, SE and Hepinstall-Cymerman, J and Yabsley, MJ and Adams, HC and Ellison, T and Welch, CN and Hernandez, SM}, title = {From wetland specialist to hand-fed generalist: shifts in diet and condition with provisioning for a recently urbanized wading bird.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531152}, issn = {1471-2970}, mesh = {Animal Feed/*supply & distribution ; Animal Migration/*physiology ; Animals ; Animals, Wild ; Birds/parasitology/*physiology ; Diet ; Dietary Proteins/administration & dosage/analysis ; Ecosystem ; Ectoparasitic Infestations/epidemiology/parasitology/*veterinary ; Feeding Behavior/*physiology ; Florida/epidemiology ; Grooming/physiology ; Mites/physiology ; Nitrogen Isotopes/metabolism ; Phthiraptera/physiology ; Population Dynamics ; Seasons ; Urbanization ; }, abstract = {Many wildlife species shift their diets to use novel resources in urban areas. The consequences of these shifts are not well known, and consumption of reliable-but low quality-anthropogenic food may present important trade-offs for wildlife health. This may be especially true for carnivorous species such as the American white ibis (Eudocimus albus), a nomadic wading bird which has been increasingly observed in urban parks in South Florida, USA. We tested the effects of anthropogenic provisioning on consumer nutrition (i.e. dietary protein), body condition and ectoparasite burdens along an urban gradient using stable isotope analysis, scaled mass index values and GPS transmitter data. Ibises that assimilated more provisioned food were captured at more urban sites, used more urban habitat, had lower mass-length residuals, lower ectoparasite scores, assimilated less δ15N and had smaller dietary isotopic ellipses. Our results suggest that ibises in urban areas are heavily provisioned with anthropogenic food, which appears to offer a trade-off by providing low-quality, but easily accessible, calories that may not support high mass but may increase time available for anti-parasite behaviours such as preening. Understanding such trade-offs is important for investigating the effects of provisioning on infection risk and the conservation of wildlife in human-modified habitats.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531151, year = {2018}, author = {Páez, DJ and Restif, O and Eby, P and Plowright, RK}, title = {Optimal foraging in seasonal environments: implications for residency of Australian flying foxes in food-subsidized urban landscapes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531151}, issn = {1471-2970}, support = {P20 GM103474/GM/NIGMS NIH HHS/United States ; P30 GM110732/GM/NIGMS NIH HHS/United States ; }, mesh = {Animal Feed/*supply & distribution ; Animal Migration/*physiology ; Animals ; Animals, Wild ; Australia ; Chiroptera/*physiology ; Cities ; Ecosystem ; Feeding Behavior/*physiology ; Flowers/physiology ; Fruit/physiology ; Plants ; Population Dynamics ; Seasons ; Time Factors ; }, abstract = {Bats provide important ecosystem services such as pollination of native forests; they are also a source of zoonotic pathogens for humans and domestic animals. Human-induced changes to native habitats may have created more opportunities for bats to reside in urban settings, thus decreasing pollination services to native forests and increasing opportunities for zoonotic transmission. In Australia, fruit bats (Pteropus spp. flying foxes) are increasingly inhabiting urban areas where they feed on anthropogenic food sources with nutritional characteristics and phenology that differ from native habitats. We use optimal foraging theory to investigate the relationship between bat residence time in a patch, the time it takes to search for a new patch (simulating loss of native habitat) and seasonal resource production. We show that it can be beneficial to reside in a patch, even when food productivity is low, as long as foraging intensity is low and the expected searching time is high. A small increase in the expected patch searching time greatly increases the residence time, suggesting nonlinear associations between patch residence and loss of seasonal native resources. We also found that sudden increases in resource consumption due to an influx of new bats has complex effects on patch departure times that again depend on expected searching times and seasonality. Our results suggest that the increased use of urban landscapes by bats may be a response to new spatial and temporal configurations of foraging opportunities. Given that bats are reservoir hosts of zoonotic diseases, our results provide a framework to study the effects of foraging ecology on disease dynamics.One contribution of 14 to a theme isssue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531150, year = {2018}, author = {Brown, LM and Hall, RJ}, title = {Consequences of resource supplementation for disease risk in a partially migratory population.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531150}, issn = {1471-2970}, mesh = {Animal Feed/*supply & distribution ; Animal Migration/*physiology ; Animals ; Animals, Wild ; Disease Susceptibility ; Ecosystem ; *Host-Pathogen Interactions ; *Models, Statistical ; Population Dynamics ; Seasons ; Songbirds/*immunology/microbiology ; Survival Analysis ; }, abstract = {Anthropogenic landscape features such as urban parks and gardens, landfills and farmlands can provide novel, seasonally reliable food sources that impact wildlife ecology and distributions. In historically migratory species, food subsidies can cause individuals to forgo migration and form partially migratory or entirely sedentary populations, eroding a crucial benefit of migration: pathogen avoidance through seasonal abandonment of transmission sites and mortality of infected individuals during migration. Since many migratory taxa are declining, and wildlife populations in urban areas can harbour zoonotic pathogens, understanding the mechanisms by which anthropogenic resource subsidies influence infection dynamics and the persistence of migration is important for wildlife conservation and public health. We developed a mathematical model for a partially migratory population and a vector-borne pathogen transmitted at a shared breeding ground, where food subsidies increase the nonbreeding survival of residents. We found that higher resident nonbreeding survival increased infection prevalence in residents and migrants, and lowered the fraction of the population that migrated. The persistence of migration may be especially threatened if residency permits emergence of more virulent pathogens, if resource subsidies reduce costs of infection for residents, and if infection reduces individual migratory propensity.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531149, year = {2018}, author = {Satterfield, DA and Marra, PP and Sillett, TS and Altizer, S}, title = {Responses of migratory species and their pathogens to supplemental feeding.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531149}, issn = {1471-2970}, mesh = {Animal Feed/*supply & distribution ; Animal Migration/*physiology ; Animals ; Animals, Wild ; Apicomplexa/pathogenicity ; Birds/*immunology/microbiology/parasitology ; Butterflies/immunology/*parasitology ; Chiroptera/*immunology/microbiology ; Deer/*immunology/microbiology/parasitology ; Ecosystem ; Host-Parasite Interactions ; Host-Pathogen Interactions ; North America ; Population Dynamics ; Seasons ; South America ; }, abstract = {Migratory animals undergo seasonal and often spectacular movements and perform crucial ecosystem services. In response to anthropogenic changes, including food subsidies, some migratory animals are now migrating shorter distances or halting migration altogether and forming resident populations. Recent studies suggest that shifts in migratory behaviour can alter the risk of infection for wildlife. Although migration is commonly assumed to enhance pathogen spread, for many species, migration has the opposite effect of lowering infection risk, if animals escape from habitats where pathogen stages have accumulated or if strenuous journeys cull infected hosts. Here, we summarize responses of migratory species to supplemental feeding and review modelling and empirical work that provides support for mechanisms through which resource-induced changes in migration can alter pathogen transmission. In particular, we focus on the well-studied example of monarch butterflies and their protozoan parasites in North America. We also identify areas for future research, including combining new technologies for tracking animal movements with pathogen surveillance and exploring potential evolutionary responses of hosts and pathogens to changing movement patterns. Given that many migratory animals harbour pathogens of conservation concern and zoonotic potential, studies that document ongoing shifts in migratory behaviour and infection risk are vitally needed.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531148, year = {2018}, author = {Cotterill, GG and Cross, PC and Cole, EK and Fuda, RK and Rogerson, JD and Scurlock, BM and du Toit, JT}, title = {Winter feeding of elk in the Greater Yellowstone Ecosystem and its effects on disease dynamics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531148}, issn = {1471-2970}, mesh = {Animal Feed/*supply & distribution ; Animals ; Animals, Wild/microbiology ; Artiodactyla/microbiology ; Brucella abortus/isolation & purification ; Brucellosis/*epidemiology/transmission/*veterinary ; Cattle ; Ecosystem ; Epidemiological Monitoring ; Population Control/methods ; Seasons ; Wasting Disease, Chronic/epidemiology/*prevention & control/transmission ; Wyoming/epidemiology ; }, abstract = {Providing food to wildlife during periods when natural food is limited results in aggregations that may facilitate disease transmission. This is exemplified in western Wyoming where institutional feeding over the past century has aimed to mitigate wildlife-livestock conflict and minimize winter mortality of elk (Cervus canadensis). Here we review research across 23 winter feedgrounds where the most studied disease is brucellosis, caused by the bacterium Brucella abortus Traditional veterinary practices (vaccination, test-and-slaughter) have thus far been unable to control this disease in elk, which can spill over to cattle. Current disease-reduction efforts are being guided by ecological research on elk movement and density, reproduction, stress, co-infections and scavengers. Given the right tools, feedgrounds could provide opportunities for adaptive management of brucellosis through regular animal testing and population-level manipulations. Our analyses of several such manipulations highlight the value of a research-management partnership guided by hypothesis testing, despite the constraints of the sociopolitical environment. However, brucellosis is now spreading in unfed elk herds, while other diseases (e.g. chronic wasting disease) are of increasing concern at feedgrounds. Therefore experimental closures of feedgrounds, reduced feeding and lower elk populations merit consideration.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531147, year = {2018}, author = {Cox, DTC and Gaston, KJ}, title = {Human-nature interactions and the consequences and drivers of provisioning wildlife.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531147}, issn = {1471-2970}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Amphibians/physiology ; Animal Feed/*supply & distribution ; Animals ; Animals, Wild/*physiology ; Birds/physiology ; Conservation of Natural Resources/*methods ; Fishes/physiology ; Humans ; Mammals/physiology ; Population Dynamics/statistics & numerical data ; *Psychosocial Deprivation ; Reptiles/physiology ; Urbanization/trends ; }, abstract = {Many human populations are undergoing an extinction of experience, with a progressive decline in interactions with nature. This is a consequence both of a loss of opportunity for, and orientation towards, such experiences. The trend is of concern in part because interactions with nature can be good for human health and wellbeing. One potential means of redressing these losses is through the intentional provision of resources to increase wildlife populations in close proximity to people, thereby increasing the potential for positive human-nature experiences, and thence the array of benefits that can result. In this paper, we review the evidence that these resource subsidies have such a cascade of effects. In some Westernized countries, the scale of provision is extraordinarily high, and doubtless leads to both positive and negative impacts for wildlife. In turn, these impacts often lead to more frequent, reliable and closer human-nature interactions, with a greater variety of species. The consequences for human wellbeing remain poorly understood, although benefits documented in the context of human-nature interactions more broadly seem likely to apply. There are also some important feedback loops that need to be better characterized if resource provisioning is to contribute effectively towards averting the extinction of experience.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531146, year = {2018}, author = {Lawson, B and Robinson, RA and Toms, MP and Risely, K and MacDonald, S and Cunningham, AA}, title = {Health hazards to wild birds and risk factors associated with anthropogenic food provisioning.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531146}, issn = {1471-2970}, mesh = {Animal Feed/supply & distribution ; Animals ; Bird Diseases/*epidemiology/immunology/transmission ; Epidemiological Monitoring ; Humans ; Immunity, Innate ; Mycotoxins/analysis ; Passeriformes/*immunology/microbiology/parasitology/virology ; Population Dynamics/statistics & numerical data ; Poxviridae Infections/epidemiology/immunology/transmission/*veterinary ; Risk Factors ; Salmonella Infections/*epidemiology/immunology/transmission ; Trichomonas Infections/epidemiology/immunology/transmission/*veterinary ; United Kingdom/epidemiology ; }, abstract = {Provision of supplementary food for wild birds at garden feeding stations is a common, large-scale and year-round practice in multiple countries including Great Britain (GB). While these additional dietary resources can benefit wildlife, there is a concomitant risk of disease transmission, particularly when birds repeatedly congregate in the same place at high densities and through interactions of species that would not normally associate in close proximity. Citizen science schemes recording garden birds are popular and can integrate disease surveillance with population monitoring, offering a unique opportunity to explore inter-relationships between supplementary feeding, disease epidemiology and population dynamics. Here, we present findings from a national surveillance programme in GB and note the dynamism of endemic and emerging diseases over a 25-year period, focusing on protozoal (finch trichomonosis), viral (Paridae pox) and bacterial (passerine salmonellosis) diseases with contrasting modes of transmission. We also examine the occurrence of mycotoxin contamination of food residues in bird feeders, which present both a direct and indirect (though immunosuppression) risk to wild bird health. Our results inform evidence-based mitigation strategies to minimize anthropogenically mediated health hazards, while maintaining the benefits of providing supplementary food for wild birds.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531145, year = {2018}, author = {Moyers, SC and Adelman, JS and Farine, DR and Thomason, CA and Hawley, DM}, title = {Feeder density enhances house finch disease transmission in experimental epidemics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531145}, issn = {1471-2970}, mesh = {Aggression ; Animal Feed/*statistics & numerical data/supply & distribution ; Animals ; Antibodies, Bacterial/blood ; Bird Diseases/*epidemiology/immunology/microbiology/transmission ; Competitive Behavior/physiology ; *Epidemics ; Female ; Finches/*immunology/microbiology ; Host-Pathogen Interactions/immunology ; Humans ; Male ; Models, Animal ; Mycoplasma Infections/immunology/microbiology/transmission/*veterinary ; Mycoplasma gallisepticum/immunology ; Virginia/epidemiology ; }, abstract = {Anthropogenic food provisioning of wildlife can alter the frequency of contacts among hosts and between hosts and environmental sources of pathogens. Despite the popularity of garden bird feeding, few studies have addressed how feeders influence host contact rates and disease dynamics. We experimentally manipulated feeder density in replicate aviaries containing captive, pathogen-naive, groups of house finches (Haemorhous mexicanus) and continuously tracked behaviours at feeders using radio-frequency identification devices. We then inoculated one bird per group with Mycoplasma gallisepticum (Mg), a common bacterial pathogen for which feeders are fomites of transmission, and assessed effects of feeder density on house finch behaviour and pathogen transmission. We found that pathogen transmission was significantly higher in groups with the highest density of bird feeders, despite a significantly lower rate of intraspecific aggressive interactions relative to the low feeder density groups. Conversely, among naive group members that never showed signs of disease, we saw significantly higher concentrations of Mg-specific antibodies in low feeder density groups, suggesting that birds in low feeder density treatments had exposure to subclinical doses of Mg. We discuss ways in which the density of garden bird feeders could play an important role in mediating the intensity of Mg epidemics.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531144, year = {2018}, author = {Becker, DJ and Czirják, GÁ and Volokhov, DV and Bentz, AB and Carrera, JE and Camus, MS and Navara, KJ and Chizhikov, VE and Fenton, MB and Simmons, NB and Recuenco, SE and Gilbert, AT and Altizer, S and Streicker, DG}, title = {Livestock abundance predicts vampire bat demography, immune profiles and bacterial infection risk.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531144}, issn = {1471-2970}, support = {102507/Z/13/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adaptive Immunity ; Animals ; Bartonella/immunology ; Bartonella Infections/epidemiology/immunology/microbiology/*veterinary ; Belize/epidemiology ; Chiroptera/*immunology/microbiology ; Eating/physiology ; Female ; Host-Pathogen Interactions/immunology ; *Immunity, Innate ; Immunoglobulin G ; Livestock/physiology ; Lymphocytes/immunology/microbiology ; Male ; Mycoplasma/immunology ; Mycoplasma Infections/epidemiology/immunology/microbiology/*veterinary ; Neutrophils/immunology/microbiology ; Peru/epidemiology ; Population Dynamics ; Reproduction/*physiology ; }, abstract = {Human activities create novel food resources that can alter wildlife-pathogen interactions. If resources amplify or dampen, pathogen transmission probably depends on both host ecology and pathogen biology, but studies that measure responses to provisioning across both scales are rare. We tested these relationships with a 4-year study of 369 common vampire bats across 10 sites in Peru and Belize that differ in the abundance of livestock, an important anthropogenic food source. We quantified innate and adaptive immunity from bats and assessed infection with two common bacteria. We predicted that abundant livestock could reduce starvation and foraging effort, allowing for greater investments in immunity. Bats from high-livestock sites had higher microbicidal activity and proportions of neutrophils but lower immunoglobulin G and proportions of lymphocytes, suggesting more investment in innate relative to adaptive immunity and either greater chronic stress or pathogen exposure. This relationship was most pronounced in reproductive bats, which were also more common in high-livestock sites, suggesting feedbacks between demographic correlates of provisioning and immunity. Infection with both Bartonella and haemoplasmas were correlated with similar immune profiles, and both pathogens tended to be less prevalent in high-livestock sites, although effects were weaker for haemoplasmas. These differing responses to provisioning might therefore reflect distinct transmission processes. Predicting how provisioning alters host-pathogen interactions requires considering how both within-host processes and transmission modes respond to resource shifts.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531143, year = {2018}, author = {Strandin, T and Babayan, SA and Forbes, KM}, title = {Reviewing the effects of food provisioning on wildlife immunity.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531143}, issn = {1471-2970}, mesh = {Adaptive Immunity/drug effects ; Animal Feed/analysis ; Animals ; Animals, Wild/*immunology/parasitology ; Birds/*immunology/parasitology ; Conservation of Natural Resources ; Ecosystem ; Food Supply/statistics & numerical data ; *Host-Parasite Interactions ; Humans ; Immunity, Innate/drug effects ; Mammals/*immunology/parasitology ; Pharmaceutical Preparations/supply & distribution ; Reptiles/*immunology/parasitology ; Trace Elements/adverse effects ; }, abstract = {While urban expansion increasingly encroaches on natural habitats, many wildlife species capitalize on anthropogenic food resources, which have the potential to both positively and negatively influence their responses to infection. Here we examine how food availability and key nutrients have been reported to shape innate and adaptive immunity in wildlife by drawing from field-based studies, as well as captive and food restriction studies with wildlife species. Examples of food provisioning and key nutrients enhancing immune function were seen across the three study type distinctions, as were cases of trace metals and pharmaceuticals impairing the immunity of wildlife species. More generally, food provisioning in field studies tended to increase innate and adaptive responses to certain immune challenges, whereas patterns were less clear in captive studies. Mild food restriction often enhanced, whereas severe food restriction frequently impaired immunity. However, to enable stronger conclusions we stress a need for further research, especially field studies, and highlight the importance of integrating nutritional manipulation, immune challenge, and functional outcomes. Despite current gaps in research on this topic, modern high throughput molecular approaches are increasingly feasible for wildlife studies and offer great opportunities to better understand human influences on wildlife health.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531142, year = {2018}, author = {Hite, JL and Cressler, CE}, title = {Resource-driven changes to host population stability alter the evolution of virulence and transmission.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531142}, issn = {1471-2970}, mesh = {Animals ; Animals, Wild/*parasitology ; *Host-Parasite Interactions ; *Life History Traits ; Models, Biological ; *Models, Statistical ; Parasites/*pathogenicity/physiology ; Population Dynamics ; Virulence ; }, abstract = {What drives the evolution of parasite life-history traits? Recent studies suggest that linking within- and between-host processes can provide key insight into both disease dynamics and parasite evolution. Still, it remains difficult to understand how to pinpoint the critical factors connecting these cross-scale feedbacks, particularly under non-equilibrium conditions; many natural host populations inherently fluctuate and parasites themselves can strongly alter the stability of host populations. Here, we develop a general model framework that mechanistically links resources to parasite evolution across a gradient of stable and unstable conditions. First, we dynamically link resources and between-host processes (host density, stability, transmission) to virulence evolution, using a 'non-nested' model. Then, we consider a 'nested' model where population-level processes (transmission and virulence) depend on resource-driven changes to individual-level (within-host) processes (energetics, immune function, parasite production). Contrary to 'non-nested' model predictions, the 'nested' model reveals complex effects of host population dynamics on parasite evolution, including regions of evolutionary bistability; evolution can push parasites towards strongly or weakly stabilizing strategies. This bistability results from dynamic feedbacks between resource-driven changes to host density, host immune function and parasite production. Together, these results highlight how cross-scale feedbacks can provide key insights into the structuring role of parasites and parasite evolution.This article is part of the theme issue 'Anthropogenic resource subsidies and host-parasite dynamics in wildlife'.}, } @article {pmid29531141, year = {2018}, author = {Becker, DJ and Hall, RJ and Forbes, KM and Plowright, RK and Altizer, S}, title = {Anthropogenic resource subsidies and host-parasite dynamics in wildlife.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1745}, pages = {}, pmid = {29531141}, issn = {1471-2970}, support = {P20 GM103474/GM/NIGMS NIH HHS/United States ; P30 GM110732/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animal Feed/analysis ; Animals ; Animals, Wild/*immunology/parasitology ; Birds/*immunology/parasitology ; Conservation of Natural Resources ; Food Supply/statistics & numerical data ; *Host-Parasite Interactions ; Humans ; Immunity, Innate ; Mammals/*immunology/parasitology ; }, } @article {pmid29531095, year = {2018}, author = {Shiffrin, RM and Börner, K and Stigler, SM}, title = {Scientific progress despite irreproducibility: A seeming paradox.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2632-2639}, pmid = {29531095}, issn = {1091-6490}, support = {P01 AG039347/AG/NIA NIH HHS/United States ; U01 CA198934/CA/NCI NIH HHS/United States ; }, mesh = {Communication ; Humans ; Laboratory Personnel/psychology/standards ; Peer Review/standards ; Publications/standards/statistics & numerical data ; Reproducibility of Results ; Research/*standards ; Science/*standards ; Workforce ; }, abstract = {It appears paradoxical that science is producing outstanding new results and theories at a rapid rate at the same time that researchers are identifying serious problems in the practice of science that cause many reports to be irreproducible and invalid. Certainly, the practice of science needs to be improved, and scientists are now pursuing this goal. However, in this perspective, we argue that this seeming paradox is not new, has always been part of the way science works, and likely will remain so. We first introduce the paradox. We then review a wide range of challenges that appear to make scientific success difficult. Next, we describe the factors that make science work-in the past, present, and presumably also in the future. We then suggest that remedies for the present practice of science need to be applied selectively so as not to slow progress and illustrate with a few examples. We conclude with arguments that communication of science needs to emphasize not just problems but the enormous successes and benefits that science has brought and is now bringing to all elements of modern society.}, } @article {pmid29531094, year = {2018}, author = {Nelp, MT and Kates, PA and Hunt, JT and Newitt, JA and Balog, A and Maley, D and Zhu, X and Abell, L and Allentoff, A and Borzilleri, R and Lewis, HA and Lin, Z and Seitz, SP and Yan, C and Groves, JT}, title = {Immune-modulating enzyme indoleamine 2,3-dioxygenase is effectively inhibited by targeting its apo-form.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3249-3254}, pmid = {29531094}, issn = {1091-6490}, support = {R37 GM036298/GM/NIGMS NIH HHS/United States ; }, mesh = {Apoproteins/chemistry ; Crystallography, X-Ray ; Dose-Response Relationship, Drug ; Enzyme Inhibitors/administration & dosage/chemistry/metabolism/*pharmacology ; HeLa Cells ; Heme/metabolism ; Humans ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*antagonists & inhibitors/*chemistry/metabolism ; Inhibitory Concentration 50 ; Myoglobin/chemistry ; }, abstract = {For cancer cells to survive and proliferate, they must escape normal immune destruction. One mechanism by which this is accomplished is through immune suppression effected by up-regulation of indoleamine 2,3-dioxygenase (IDO1), a heme enzyme that catalyzes the oxidation of tryptophan to N-formylkynurenine. On deformylation, kynurenine and downstream metabolites suppress T cell function. The importance of this immunosuppressive mechanism has spurred intense interest in the development of clinical IDO1 inhibitors. Herein, we describe the mechanism by which a class of compounds effectively and specifically inhibits IDO1 by targeting its apo-form. We show that the in vitro kinetics of inhibition coincide with an unusually high rate of intrinsic enzyme-heme dissociation, especially in the ferric form. X-ray crystal structures of the inhibitor-enzyme complexes show that heme is displaced from the enzyme and blocked from rebinding by these compounds. The results reveal that apo-IDO1 serves as a unique target for inhibition and that heme lability plays an important role in posttranslational regulation.}, } @article {pmid29531093, year = {2018}, author = {}, title = {Correction for Hoffecker, The complexity of Neanderthal technology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3066}, doi = {10.1073/pnas.1803330115}, pmid = {29531093}, issn = {1091-6490}, } @article {pmid29531092, year = {2018}, author = {Baribault, B and Donkin, C and Little, DR and Trueblood, JS and Oravecz, Z and van Ravenzwaaij, D and White, CN and De Boeck, P and Vandekerckhove, J}, title = {Metastudies for robust tests of theory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2607-2612}, pmid = {29531092}, issn = {1091-6490}, mesh = {Bayes Theorem ; Biomedical Research/*standards ; Data Interpretation, Statistical ; Humans ; Random Allocation ; Research Design/*standards ; }, abstract = {We describe and demonstrate an empirical strategy useful for discovering and replicating empirical effects in psychological science. The method involves the design of a metastudy, in which many independent experimental variables-that may be moderators of an empirical effect-are indiscriminately randomized. Radical randomization yields rich datasets that can be used to test the robustness of an empirical claim to some of the vagaries and idiosyncrasies of experimental protocols and enhances the generalizability of these claims. The strategy is made feasible by advances in hierarchical Bayesian modeling that allow for the pooling of information across unlike experiments and designs and is proposed here as a gold standard for replication research and exploratory research. The practical feasibility of the strategy is demonstrated with a replication of a study on subliminal priming.}, } @article {pmid29531091, year = {2018}, author = {Nosek, BA and Ebersole, CR and DeHaven, AC and Mellor, DT}, title = {The preregistration revolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2600-2606}, pmid = {29531091}, issn = {1091-6490}, mesh = {Humans ; Laboratory Personnel/standards ; Predictive Value of Tests ; Research/*standards ; Science/*standards ; Workforce ; }, abstract = {Progress in science relies in part on generating hypotheses with existing observations and testing hypotheses with new observations. This distinction between postdiction and prediction is appreciated conceptually but is not respected in practice. Mistaking generation of postdictions with testing of predictions reduces the credibility of research findings. However, ordinary biases in human reasoning, such as hindsight bias, make it hard to avoid this mistake. An effective solution is to define the research questions and analysis plan before observing the research outcomes-a process called preregistration. Preregistration distinguishes analyses and outcomes that result from predictions from those that result from postdictions. A variety of practical strategies are available to make the best possible use of preregistration in circumstances that fall short of the ideal application, such as when the data are preexisting. Services are now available for preregistration across all disciplines, facilitating a rapid increase in the practice. Widespread adoption of preregistration will increase distinctiveness between hypothesis generation and hypothesis testing and will improve the credibility of research findings.}, } @article {pmid29531090, year = {2018}, author = {Kumar, A and Gopalswamy, M and Wolf, A and Brockwell, DJ and Hatzfeld, M and Balbach, J}, title = {Phosphorylation-induced unfolding regulates p19INK4d during the human cell cycle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3344-3349}, pmid = {29531090}, issn = {1091-6490}, mesh = {Cell Cycle/*physiology ; Cell Division ; Cyclin-Dependent Kinase Inhibitor p19/*chemistry/*metabolism ; HEK293 Cells ; HeLa Cells ; Humans ; Models, Molecular ; Phosphorylation ; Protein Conformation ; *Protein Unfolding ; Proteolysis ; Signal Transduction ; }, abstract = {Cell cycle progression is tightly regulated by cyclin-dependent kinases (CDKs). The ankyrin-repeat protein p19INK4d functions as a key regulator of G1/S transition; however, its molecular mode of action is unknown. Here, we combine cell and structural biology methods to unravel the mechanism by which p19INK4d controls cell cycle progression. We delineate how the stepwise phosphorylation of p19INK4d Ser66 and Ser76 by cell cycle-independent (p38) and -dependent protein kinases (CDK1), respectively, leads to local unfolding of the three N-terminal ankyrin repeats of p19INK4d This dissociates the CDK6-p19INK4d inhibitory complex and, thereby, activates CDK6. CDK6 triggers entry into S-phase, whereas p19INK4d is ubiquitinated and degraded. Our findings reveal how signaling-dependent p19INK4d unfolding contributes to the irreversibility of G1/S transition.}, } @article {pmid29531089, year = {2018}, author = {}, title = {Retraction for Skau et al., Inverted formin 2 in focal adhesions promotes dorsal stress fiber and fibrillar adhesion formation to drive extracellular matrix assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2900}, doi = {10.1073/pnas.1803125115}, pmid = {29531089}, issn = {1091-6490}, } @article {pmid29531088, year = {2018}, author = {Widman, AJ and McMahon, LL}, title = {Disinhibition of CA1 pyramidal cells by low-dose ketamine and other antagonists with rapid antidepressant efficacy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3007-E3016}, pmid = {29531088}, issn = {1091-6490}, support = {F31 MH110096/MH/NIMH NIH HHS/United States ; R56 MH107190/MH/NIMH NIH HHS/United States ; }, mesh = {Action Potentials/*drug effects ; Animals ; Antidepressive Agents/*pharmacology ; Depressive Disorder/*drug therapy/pathology ; Excitatory Amino Acid Antagonists/pharmacology ; Hippocampus/drug effects/metabolism ; Interneurons/drug effects/metabolism ; Ketamine/*pharmacology ; Male ; Neuronal Plasticity/drug effects ; Pyramidal Cells/*drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/*antagonists & inhibitors ; Scopolamine/pharmacology ; Synapses/drug effects/metabolism ; }, abstract = {Low-dose ketamine, an open-channel N-methyl d-aspartate receptor (NMDAR) antagonist, mediates rapid antidepressant effects in humans that are mimicked in preclinical rodent models. Disinhibition of pyramidal cells via decreased output of fast-spiking GABAergic interneurons has been proposed as a key mechanism that triggers the antidepressant response. Unfortunately, to date, disinhibition has not been directly demonstrated. Furthermore, whether disinhibition is a common mechanism shared among other antagonists with rapid antidepressant properties in humans has not been investigated. Using in vitro electrophysiology in acute slices of dorsal hippocampus from adult male Sprague-Dawley rats, we examined the immediate effects of a clinically relevant concentration of ketamine to directly test the disinhibition hypothesis. As a mechanistic comparison, we also tested the effects of the glycine site NMDAR partial agonist/antagonist GLYX-13 (rapastinel), the GluN2B subunit-selective NMDAR antagonist Ro 25-6981, and the muscarinic acetylcholine receptor (mAChR) antagonist scopolamine. Low-dose ketamine, GLYX-13, and scopolamine reduced inhibitory input onto pyramidal cells and increased synaptically driven pyramidal cell excitability measured at the single-cell and population levels. Conversely, Ro 25-6981 increased the strength of inhibitory transmission and did not change pyramidal cell excitability. These results show a decrease in the inhibition/excitation balance that supports disinhibition as a common mechanism shared among those antagonists with rapid antidepressant properties. These data suggest that pyramidal cell disinhibition downstream of NMDAR antagonism could serve as a possible biomarker for the efficacy of rapid antidepressant therapy.}, } @article {pmid29531087, year = {2018}, author = {Haj-Dahmane, S and Shen, RY and Elmes, MW and Studholme, K and Kanjiya, MP and Bogdan, D and Thanos, PK and Miyauchi, JT and Tsirka, SE and Deutsch, DG and Kaczocha, M}, title = {Fatty-acid-binding protein 5 controls retrograde endocannabinoid signaling at central glutamate synapses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3482-3487}, pmid = {29531087}, issn = {1091-6490}, support = {F30 CA196110/CA/NCI NIH HHS/United States ; R01 DA035923/DA/NIDA NIH HHS/United States ; R01 DA035949/DA/NIDA NIH HHS/United States ; R01 MH078009/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Arachidonic Acids/*metabolism ; Cells, Cultured ; Endocannabinoids/metabolism/*pharmacology ; Fatty Acid-Binding Proteins/*physiology ; Glutamic Acid/*metabolism ; Glycerides/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasm Proteins/*physiology ; Rats ; Rats, Sprague-Dawley ; Receptor, Cannabinoid, CB1/metabolism ; Synapses/drug effects/*physiology ; Synaptic Transmission/*drug effects ; }, abstract = {Endocannabinoids (eCBs) are lipid-signaling molecules involved in the regulation of numerous behaviors and physiological functions. Released by postsynaptic neurons, eCBs mediate retrograde modulation of synaptic transmission and plasticity by activating presynaptic cannabinoid receptors. While the cellular mechanisms by which eCBs control synaptic function have been well characterized, the mechanisms controlling their retrograde synaptic transport remain unknown. Here, we demonstrate that fatty-acid-binding protein 5 (FABP5), a canonical intracellular carrier of eCBs, is indispensable for retrograde eCB transport in the dorsal raphe nucleus (DRn). Thus, pharmacological inhibition or genetic deletion of FABP5 abolishes both phasic and tonic eCB-mediated control of excitatory synaptic transmission in the DRn. The blockade of retrograde eCB signaling induced by FABP5 inhibition is not mediated by impaired cannabinoid receptor function or reduced eCB synthesis. These findings indicate that FABP5 is essential for retrograde eCB signaling and may serve as a synaptic carrier of eCBs at central synapses.}, } @article {pmid29531086, year = {2018}, author = {Dickersin, K and Mayo-Wilson, E}, title = {Standards for design and measurement would make clinical research reproducible and usable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2590-2594}, pmid = {29531086}, issn = {1091-6490}, mesh = {Clinical Protocols/*standards ; Clinical Trials as Topic/*standards ; Humans ; Information Dissemination ; Reproducibility of Results ; Research Design/*standards ; }, abstract = {We find standards useful in everyday life and in science, although we do not always follow them. Adopting new standards can be expensive, so there may be a strong incentive to maintain the status quo rather than adopt new standards. The scientific community has many standards encompassing both doing clinical research and reporting it, including standards for design and measurement. Although existing research standards have improved both research and its reporting, we need to unify existing standards and to fill the gaps between steps throughout the research process. Existing gaps include implementation of standards and links between standards for study registration (to know about all studies undertaken), study protocols (to identify the preplanned study design and methods), data collection (to assess outcomes that are important and comparable across studies), dissemination of findings (to know the results of previous studies), data sharing (to make best use of existing data), and evidence synthesis (to draw appropriate conclusions from the body of evidence). The scientific community must work together to harmonize existing standards, to ensure that standards are kept up to date, to check that standards are followed, and to develop standards where they are still needed. A unified system of standards will make our work more reproducible.}, } @article {pmid29531085, year = {2018}, author = {Drayton, LA and Santos, LR and Baskin-Sommers, A}, title = {Psychopaths fail to automatically take the perspective of others.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3302-3307}, pmid = {29531085}, issn = {1091-6490}, support = {UL1 TR001863/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antisocial Personality Disorder/*etiology/psychology ; Cognition Disorders/*complications ; Criminals/*psychology/statistics & numerical data ; Female ; Hostility ; Humans ; Male ; Middle Aged ; Psychopathology ; *Social Perception ; *Theory of Mind ; Young Adult ; }, abstract = {Psychopathic individuals display a chronic and flagrant disregard for the welfare of others through their callous and manipulative behavior. Historically, this behavior is thought to result from deficits in social-affective processing. However, we show that at least some psychopathic behaviors may be rooted in a cognitive deficit, specifically an inability to automatically take another person's perspective. Unlike prior studies that rely solely on controlled theory of mind (ToM) tasks, we employ a task that taps into automatic ToM processing. Controlled ToM processes are engaged when an individual intentionally considers the perspective of another person, whereas automatic ToM processes are engaged when an individual unintentionally represents the perspective of another person. In a sample of incarcerated offenders, we find that psychopathic individuals are equally likely to show response interference under conditions of controlled ToM, but lack a common signature of automatic ToM known as altercentric interference. We also demonstrate that the magnitude of this dysfunction in altercentric interference is correlated with real-world callous behaviors (i.e., number of assault charges). These findings suggest that psychopathic individuals have a diminished propensity to automatically think from another's perspective, which may be the cognitive root of their deficits in social functioning and moral behavior.}, } @article {pmid29531084, year = {2018}, author = {Haldon, J and Mordechai, L and Newfield, TP and Chase, AF and Izdebski, A and Guzowski, P and Labuhn, I and Roberts, N}, title = {History meets palaeoscience: Consilience and collaboration in studying past societal responses to environmental change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3210-3218}, pmid = {29531084}, issn = {1091-6490}, abstract = {History and archaeology have a well-established engagement with issues of premodern societal development and the interaction between physical and cultural environments; together, they offer a holistic view that can generate insights into the nature of cultural resilience and adaptation, as well as responses to catastrophe. Grasping the challenges that climate change presents and evolving appropriate policies that promote and support mitigation and adaptation requires not only an understanding of the science and the contemporary politics, but also an understanding of the history of the societies affected and in particular of their cultural logic. But whereas archaeologists have developed productive links with the paleosciences, historians have, on the whole, remained muted voices in the debate until recently. Here, we suggest several ways in which a consilience between the historical sciences and the natural sciences, including attention to even distant historical pasts, can deepen contemporary understanding of environmental change and its effects on human societies.}, } @article {pmid29531083, year = {2018}, author = {Vögeli, B and Engilberge, S and Girard, E and Riobé, F and Maury, O and Erb, TJ and Shima, S and Wagner, T}, title = {Archaeal acetoacetyl-CoA thiolase/HMG-CoA synthase complex channels the intermediate via a fused CoA-binding site.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3380-3385}, pmid = {29531083}, issn = {1091-6490}, mesh = {Acetyl Coenzyme A/*metabolism ; Acetyl-CoA C-Acetyltransferase/*chemistry/*metabolism ; Acyl Coenzyme A/*metabolism ; Archaea/*enzymology ; Binding Sites ; Catalysis ; Catalytic Domain ; Crystallography, X-Ray ; Hydroxymethylglutaryl-CoA Synthase/*chemistry/*metabolism ; Protein Conformation ; }, abstract = {Many reactions within a cell are thermodynamically unfavorable. To efficiently run some of those endergonic reactions, nature evolved intermediate-channeling enzyme complexes, in which the products of the first endergonic reactions are immediately consumed by the second exergonic reactions. Based on this concept, we studied how archaea overcome the unfavorable first reaction of isoprenoid biosynthesis-the condensation of two molecules of acetyl-CoA to acetoacetyl-CoA catalyzed by acetoacetyl-CoA thiolases (thiolases). We natively isolated an enzyme complex comprising the thiolase and 3-hydroxy-3-methylglutaryl (HMG)-CoA synthase (HMGCS) from a fast-growing methanogenic archaeon, Methanothermococcus thermolithotrophicus HMGCS catalyzes the second reaction in the mevalonate pathway-the exergonic condensation of acetoacetyl-CoA and acetyl-CoA to HMG-CoA. The 380-kDa crystal structure revealed that both enzymes are held together by a third protein (DUF35) with so-far-unknown function. The active-site clefts of thiolase and HMGCS form a fused CoA-binding site, which allows for efficient coupling of the endergonic thiolase reaction with the exergonic HMGCS reaction. The tripartite complex is found in almost all archaeal genomes and in some bacterial ones. In addition, the DUF35 proteins are also important for polyhydroxyalkanoate (PHA) biosynthesis, most probably by functioning as a scaffold protein that connects thiolase with 3-ketoacyl-CoA reductase. This natural and highly conserved enzyme complex offers great potential to improve isoprenoid and PHA biosynthesis in biotechnologically relevant organisms.}, } @article {pmid29531082, year = {2018}, author = {Genzel, D and Schutte, M and Brimijoin, WO and MacNeilage, PR and Wiegrebe, L}, title = {Psychophysical evidence for auditory motion parallax.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {16}, pages = {4264-4269}, pmid = {29531082}, issn = {1091-6490}, mesh = {Acoustic Stimulation ; Adult ; Cues ; Depth Perception/*physiology ; Female ; Head Movements/physiology ; Humans ; Motion ; Proprioception/*physiology ; Psychoacoustics ; Sound Localization/*physiology ; Vestibule, Labyrinth/*physiology ; Young Adult ; }, abstract = {Distance is important: From an ecological perspective, knowledge about the distance to either prey or predator is vital. However, the distance of an unknown sound source is particularly difficult to assess, especially in anechoic environments. In vision, changes in perspective resulting from observer motion produce a reliable, consistent, and unambiguous impression of depth known as motion parallax. Here we demonstrate with formal psychophysics that humans can exploit auditory motion parallax, i.e., the change in the dynamic binaural cues elicited by self-motion, to assess the relative depths of two sound sources. Our data show that sensitivity to relative depth is best when subjects move actively; performance deteriorates when subjects are moved by a motion platform or when the sound sources themselves move. This is true even though the dynamic binaural cues elicited by these three types of motion are identical. Our data demonstrate a perceptual strategy to segregate intermittent sound sources in depth and highlight the tight interaction between self-motion and binaural processing that allows assessment of the spatial layout of complex acoustic scenes.}, } @article {pmid29531081, year = {2018}, author = {Baik, E and Sanchez, DL and Turner, PA and Mach, KJ and Field, CB and Benson, SM}, title = {Geospatial analysis of near-term potential for carbon-negative bioenergy in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3290-3295}, doi = {10.1073/pnas.1720338115}, pmid = {29531081}, issn = {1091-6490}, mesh = {Biodegradation, Environmental ; *Bioengineering ; Biofuels ; *Biomass ; Carbon/*metabolism ; Carbon Dioxide/*isolation & purification ; *Carbon Sequestration ; Climate Change ; Conservation of Energy Resources ; *Environmental Monitoring ; Humans ; United States ; }, abstract = {Bioenergy with carbon capture and storage (BECCS) is a negative-emissions technology that may play a crucial role in climate change mitigation. BECCS relies on the capture and sequestration of carbon dioxide (CO2) following bioenergy production to remove and reliably sequester atmospheric CO2 Previous BECCS deployment assessments have largely overlooked the potential lack of spatial colocation of suitable storage basins and biomass availability, in the absence of long-distance biomass and CO2 transport. These conditions could constrain the near-term technical deployment potential of BECCS due to social and economic barriers that exist for biomass and CO2 transport. This study leverages biomass production data and site-specific injection and storage capacity estimates at high spatial resolution to assess the near-term deployment opportunities for BECCS in the United States. If the total biomass resource available in the United States was mobilized for BECCS, an estimated 370 Mt CO2⋅y-1 of negative emissions could be supplied in 2020. However, the absence of long-distance biomass and CO2 transport, as well as limitations imposed by unsuitable regional storage and injection capacities, collectively decrease the technical potential of negative emissions to 100 Mt CO2⋅y-1 Meeting this technical potential may require large-scale deployment of BECCS technology in more than 1,000 counties, as well as widespread deployment of dedicated energy crops. Specifically, the Illinois basin, Gulf region, and western North Dakota have the greatest potential for near-term BECCS deployment. High-resolution spatial assessment as conducted in this study can inform near-term opportunities that minimize social and economic barriers to BECCS deployment.}, } @article {pmid29531080, year = {2018}, author = {Gao, X and Cao, Q and Cheng, Y and Zhao, D and Wang, Z and Yang, H and Wu, Q and You, L and Wang, Y and Lin, Y and Li, X and Wang, Y and Bian, JS and Sun, D and Kong, L and Birnbaumer, L and Yang, Y}, title = {Chronic stress promotes colitis by disturbing the gut microbiota and triggering immune system response.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2960-E2969}, pmid = {29531080}, issn = {1091-6490}, support = {Z01 ES101684/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Colitis/*etiology/pathology ; Dextran Sulfate/toxicity ; Disease Models, Animal ; Gastrointestinal Microbiome/*immunology ; Immunity, Innate/*immunology ; Inflammation/*etiology/pathology ; Interleukin-6/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mucin-2/metabolism ; Muramidase/metabolism ; STAT3 Transcription Factor/metabolism ; *Stress, Physiological ; }, abstract = {Chronic stress is known to promote inflammatory bowel disease (IBD), but the underlying mechanism remains largely unresolved. Here, we found chronic stress to sensitize mice to dextran sulfate sodium (DSS)-induced colitis; to increase the infiltration of B cells, neutrophils, and proinflammatory ly6Chi macrophages in colonic lamina propria; and to present with decreased thymus and mesenteric lymph node (MLN) coefficients. Circulating total white blood cells were significantly increased after stress, and the proportion of MLN-associated immune cells were largely changed. Results showed a marked activation of IL-6/STAT3 signaling by stress. The detrimental action of stress was not terminated in IL-6-/- mice. Interestingly, the composition of gut microbiota was dramatically changed after stress, with expansion of inflammation-promoting bacteria. Furthermore, results showed stress-induced deficient expression of mucin-2 and lysozyme, which may contribute to the disorder of gut microbiota. Of note is that, in the case of cohousing, the stress-induced immune reaction and decreased body weight were abrogated, and transferred gut microbiota from stressed mice to control mice was sufficient to facilitate DSS-induced colitis. The important role of gut microbiota was further reinforced by broad-spectrum antibiotic treatment. Taken together, our results reveal that chronic stress disturbs gut microbiota, triggering immune system response and facilitating DSS-induced colitis.}, } @article {pmid29531079, year = {2018}, author = {Brown, AW and Kaiser, KA and Allison, DB}, title = {Issues with data and analyses: Errors, underlying themes, and potential solutions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2563-2570}, pmid = {29531079}, issn = {1091-6490}, support = {R25 GM116167/GM/NIGMS NIH HHS/United States ; R25 DK099080/DK/NIDDK NIH HHS/United States ; P30 AG050886/AG/NIA NIH HHS/United States ; P30 DK056336/DK/NIDDK NIH HHS/United States ; R25 HL124208/HL/NHLBI NIH HHS/United States ; }, mesh = {*Data Collection/standards/statistics & numerical data ; Humans ; Quality Control ; Reproducibility of Results ; *Research Design/standards/statistics & numerical data ; Science/standards/statistics & numerical data ; *Scientific Experimental Error ; Statistics as Topic/*standards ; }, abstract = {Some aspects of science, taken at the broadest level, are universal in empirical research. These include collecting, analyzing, and reporting data. In each of these aspects, errors can and do occur. In this work, we first discuss the importance of focusing on statistical and data errors to continually improve the practice of science. We then describe underlying themes of the types of errors and postulate contributing factors. To do so, we describe a case series of relatively severe data and statistical errors coupled with surveys of some types of errors to better characterize the magnitude, frequency, and trends. Having examined these errors, we then discuss the consequences of specific errors or classes of errors. Finally, given the extracted themes, we discuss methodological, cultural, and system-level approaches to reducing the frequency of commonly observed errors. These approaches will plausibly contribute to the self-critical, self-correcting, ever-evolving practice of science, and ultimately to furthering knowledge.}, } @article {pmid29531078, year = {2018}, author = {Veetil, AT and Jani, MS and Krishnan, Y}, title = {Chemical control over membrane-initiated steroid signaling with a DNA nanocapsule.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9432-9437}, pmid = {29531078}, issn = {1091-6490}, support = {UL1 TR000430/TR/NCATS NIH HHS/United States ; }, mesh = {Calcium/metabolism ; Cell Membrane/*metabolism ; Cells, Cultured ; DNA/*chemistry ; Estradiol/metabolism ; Estrogen Receptor alpha/metabolism ; Human Umbilical Vein Endothelial Cells/drug effects/metabolism ; Humans ; Models, Biological ; Nanocapsules/*chemistry ; Nanotechnology/methods ; Nitric Oxide/metabolism ; *Signal Transduction ; Steroids/*metabolism ; Sulfhydryl Compounds/pharmacology ; }, abstract = {Membrane-initiated steroid signaling (MISS) is a recently discovered aspect of steroidal control over cell function that has proved highly challenging to study due to its rapidity and ultrasensitivity to the steroid trigger [Chow RWY, Handelsman DJ, Ng MKC (2010) Endocrinology 151:2411-2422]. Fundamental aspects underlying MISS, such as receptor binding, kinetics of ion-channel opening, and production of downstream effector molecules remain obscure because a pristine molecular technology that could trigger the release of signaling steroids was not available. We have recently described a prototype DNA nanocapsule which can be programmed to release small molecules upon photoirradiation [Veetil AT, et al. (2017) Nat Nanotechnol 12:1183-1189]. Here we show that this DNA-based molecular technology can now be programmed to chemically trigger MISS, significantly expanding its applicability to systems that are refractory to photoirradiation.}, } @article {pmid29531077, year = {2018}, author = {Zhang, JY and Wang, M and Tian, L and Genovese, G and Yan, P and Wilson, JG and Thadhani, R and Mottl, AK and Appel, GB and Bick, AG and Sampson, MG and Alper, SL and Friedman, DJ and Pollak, MR}, title = {UBD modifies APOL1-induced kidney disease risk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3446-3451}, pmid = {29531077}, issn = {1091-6490}, support = {R01 DK054931/DK/NIDDK NIH HHS/United States ; R01 MD007898/MD/NIMHD NIH HHS/United States ; R56 DK054931/DK/NIDDK NIH HHS/United States ; HHSN268201300048C/HL/NHLBI NIH HHS/United States ; HHSN268201300049C/HL/NHLBI NIH HHS/United States ; R01 MD007092/MD/NIMHD NIH HHS/United States ; HHSN268201300047C/HL/NHLBI NIH HHS/United States ; HHSN268201300050C/HL/NHLBI NIH HHS/United States ; R01 DK108805/DK/NIDDK NIH HHS/United States ; HHSN268201300046C/HL/NHLBI NIH HHS/United States ; U54 GM115428/GM/NIGMS NIH HHS/United States ; }, mesh = {African Americans/*statistics & numerical data ; Alleles ; Apolipoprotein L1/*genetics ; Genetic Predisposition to Disease ; Genotype ; Glomerulosclerosis, Focal Segmental/ethnology/*genetics/*pathology ; Humans ; *Polymorphism, Single Nucleotide ; Risk Factors ; Ubiquitins/genetics/*metabolism ; }, abstract = {People of recent African ancestry develop kidney disease at much higher rates than most other groups. Two specific coding variants in the Apolipoprotein-L1 gene APOL1 termed G1 and G2 are the causal drivers of much of this difference in risk, following a recessive pattern of inheritance. However, most individuals with a high-risk APOL1 genotype do not develop overt kidney disease, prompting interest in identifying those factors that interact with APOL1 We performed an admixture mapping study to identify genetic modifiers of APOL1-associated kidney disease. Individuals with two APOL1 risk alleles and focal segmental glomerulosclerosis (FSGS) have significantly increased African ancestry at the UBD (also known as FAT10) locus. UBD is a ubiquitin-like protein modifier that targets proteins for proteasomal degradation. African ancestry at the UBD locus correlates with lower levels of UBD expression. In cell-based experiments, the disease-associated APOL1 alleles (known as G1 and G2) lead to increased abundance of UBD mRNA but to decreased levels of UBD protein. UBD gene expression inversely correlates with G1 and G2 APOL1-mediated cell toxicity, as well as with levels of G1 and G2 APOL1 protein in cells. These studies support a model whereby inflammatory stimuli up-regulate both UBD and APOL1, which interact in a functionally important manner. UBD appears to mitigate APOL1-mediated toxicity by targeting it for destruction. Thus, genetically encoded differences in UBD and UBD expression appear to modify the APOL1-associated kidney phenotype.}, } @article {pmid29531076, year = {2018}, author = {Jamieson, KH}, title = {Crisis or self-correction: Rethinking media narratives about the well-being of science.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2620-2627}, pmid = {29531076}, issn = {1091-6490}, abstract = {After documenting the existence and exploring some implications of three alternative news narratives about science and its challenges, this essay outlines ways in which those who communicate science can more accurately convey its investigatory process, self-correcting norms, and remedial actions, without in the process legitimizing an unwarranted "science is broken/in crisis" narrative. The three storylines are: (i) quest discovery, which features scientists producing knowledge through an honorable journey; (ii) counterfeit quest discovery, which centers on an individual or group of scientists producing a spurious finding through a dishonorable one; and (iii) a systemic problem structure, which suggests that some of the practices that protect science are broken, or worse, that science is no longer self-correcting or in crisis.}, } @article {pmid29531075, year = {2018}, author = {Katsu, Y and Baker, ME}, title = {Progesterone activation of zebrafish mineralocorticoid receptor may influence growth of some transplanted tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2908-E2909}, pmid = {29531075}, issn = {1091-6490}, mesh = {Aldosterone ; Animals ; Humans ; Mineralocorticoid Receptor Antagonists ; Neoplasms ; *Progesterone ; *Receptors, Mineralocorticoid ; Zebrafish ; }, } @article {pmid29531074, year = {2018}, author = {Fior, R and Ferreira, MG}, title = {Reply to Katsu and Baker: Using zebrafish PDX to screen drug sensitivity of endocrine-dependent cancers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2910}, pmid = {29531074}, issn = {1091-6490}, mesh = {Animals ; Homeodomain Proteins ; Humans ; *Neoplasms ; Trans-Activators ; *Zebrafish ; }, } @article {pmid29531073, year = {2018}, author = {Mobadersany, P and Yousefi, S and Amgad, M and Gutman, DA and Barnholtz-Sloan, JS and Velázquez Vega, JE and Brat, DJ and Cooper, LAD}, title = {Predicting cancer outcomes from histology and genomics using convolutional networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2970-E2979}, pmid = {29531073}, issn = {1091-6490}, support = {K22 LM011576/LM/NLM NIH HHS/United States ; U24 CA194362/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Brain Neoplasms/*genetics/*pathology/therapy ; Genomics/*methods ; Glioma/*genetics/*pathology/therapy ; Histological Techniques/*methods ; Humans ; Image Processing, Computer-Assisted ; *Neural Networks (Computer) ; Precision Medicine ; Prognosis ; }, abstract = {Cancer histology reflects underlying molecular processes and disease progression and contains rich phenotypic information that is predictive of patient outcomes. In this study, we show a computational approach for learning patient outcomes from digital pathology images using deep learning to combine the power of adaptive machine learning algorithms with traditional survival models. We illustrate how these survival convolutional neural networks (SCNNs) can integrate information from both histology images and genomic biomarkers into a single unified framework to predict time-to-event outcomes and show prediction accuracy that surpasses the current clinical paradigm for predicting the overall survival of patients diagnosed with glioma. We use statistical sampling techniques to address challenges in learning survival from histology images, including tumor heterogeneity and the need for large training cohorts. We also provide insights into the prediction mechanisms of SCNNs, using heat map visualization to show that SCNNs recognize important structures, like microvascular proliferation, that are related to prognosis and that are used by pathologists in grading. These results highlight the emerging role of deep learning in precision medicine and suggest an expanding utility for computational analysis of histology in the future practice of pathology.}, } @article {pmid29531072, year = {2018}, author = {Schnitzbauer, J and Wang, Y and Zhao, S and Bakalar, M and Nuwal, T and Chen, B and Huang, B}, title = {Correlation analysis framework for localization-based superresolution microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3219-3224}, pmid = {29531072}, issn = {1091-6490}, support = {DP2 OD008479/OD/NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; DNA/analysis/chemistry ; Drosophila/cytology ; Drosophila Proteins/metabolism ; Fluorescent Dyes/chemistry ; Golgi Apparatus/chemistry/metabolism ; Golgi Matrix Proteins ; Image Processing, Computer-Assisted/*methods ; Membrane Proteins/metabolism ; Microscopy, Fluorescence/*methods ; Molecular Imaging/methods ; Spatio-Temporal Analysis ; }, abstract = {Superresolution images reconstructed from single-molecule localizations can reveal cellular structures close to the macromolecular scale and are now being used routinely in many biomedical research applications. However, because of their coordinate-based representation, a widely applicable and unified analysis platform that can extract a quantitative description and biophysical parameters from these images is yet to be established. Here, we propose a conceptual framework for correlation analysis of coordinate-based superresolution images using distance histograms. We demonstrate the application of this concept in multiple scenarios, including image alignment, tracking of diffusing molecules, as well as for quantification of colocalization, showing its superior performance over existing approaches.}, } @article {pmid29531071, year = {2018}, author = {Sun, Z and Basov, DN and Fogler, MM}, title = {Universal linear and nonlinear electrodynamics of a Dirac fluid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3285-3289}, pmid = {29531071}, issn = {1091-6490}, abstract = {A general relation is derived between the linear and second-order nonlinear ac conductivities of an electron system in the hydrodynamic regime of frequencies below the interparticle scattering rate. The magnitude and tensorial structure of the hydrodynamic nonlinear conductivity are shown to differ from their counterparts in the more familiar kinetic regime of higher frequencies. Due to universality of the hydrodynamic equations, the obtained formulas are valid for systems with an arbitrary Dirac-like dispersion, ranging from solid-state electron gases to free-space plasmas, either massive or massless, at any temperature, chemical potential, or space dimension. Predictions for photon drag and second-harmonic generation in graphene are presented as one application of this theory.}, } @article {pmid29531070, year = {2018}, author = {Stanko, K and Iwert, C and Appelt, C and Vogt, K and Schumann, J and Strunk, FJ and Ahrlich, S and Schlickeiser, S and Romagnani, C and Jürchott, K and Meisel, C and Willimsky, G and Kühl, AA and Sawitzki, B}, title = {CD96 expression determines the inflammatory potential of IL-9-producing Th9 cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2940-E2949}, pmid = {29531070}, issn = {1091-6490}, mesh = {Animals ; Antigens, CD/genetics/*metabolism ; Cells, Cultured ; Colitis/*immunology/metabolism/pathology ; Dendritic Cells/immunology/metabolism ; Gene Expression Profiling ; Graft Rejection ; Homeodomain Proteins/physiology ; Humans ; Inflammation/*immunology/metabolism/pathology ; Interleukin-9/genetics/*metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Signal Transduction ; Single-Cell Analysis ; Skin Transplantation ; T-Lymphocytes, Helper-Inducer/*immunology/metabolism ; }, abstract = {Recent findings demonstrated proinflammatory functions of interleukin (IL)-9-producing T helper type (Th) 9 cells in the pathogenesis of intestinal bowel diseases (IBDs). However, also antiinflammatory properties have been ascribed to Th9 cells, pointing to a functional heterogeneity. To dissect the specific expression pattern and, especially, diversity of murine antigen-specific Th9 cells, we applied single cell transcription profiling. Th9 cells displayed reduced expression of typical activation markers, such as Cd40 ligand and Cd96, whereas expression of Cd25 and Cd83 was increased compared with other Th subsets. Importantly, we identified two subsets of Th9 cells differing above all in their CD96 expression. The heterogeneous CD96 expression was specific for Th9 cells and not observed for other Th subtypes, such as Th1 cells. Lower CD96 expression was also observed in human IL-9+ compared with IFN-γ+ T cells. Although Il9 was highly transcribed by all Th9 cells, IL-9 mRNA and protein expression was increased in CD96low cells. Transfer of CD96low Th9 cells into recombination activating gene 1-deficient (Rag1-/-) mice caused severe weight loss, intestinal and colonic inflammation, and destruction of allogeneic skin grafts and thus showed high inflammatory potential. This was associated with their expansion and tissue accumulation. Contrastingly, CD96high Th9 cells did not cause colitis and showed reduced expansion and migratory potential. Blockade of CD96 completely restored the expansion and inflammatory properties of CD96high Th9 cells. Collectively, our data suggest an inhibitory role for the cosignaling receptor CD96 in Th9 cells, raising new opportunities in the treatment of IL-9-associated inflammations such as IBD.}, } @article {pmid29531069, year = {2018}, author = {Zhang, Y and Chen, JS and Ma, J and Ni, J and Imai, M and Michioka, C and Hadano, Y and Avila, MA and Takabatake, T and Li, S and Yoshimura, K}, title = {Transitions from a Kondo-like diamagnetic insulator into a modulated ferromagnetic metal in FeGa3-yGey.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3273-3278}, pmid = {29531069}, issn = {1091-6490}, abstract = {One initial and essential question of magnetism is whether the magnetic properties of a material are governed by localized moments or itinerant electrons. Here, we expose the case for the weakly ferromagnetic system FeGa3-y Ge y , wherein these two opposite models are reconciled, such that the magnetic susceptibility is quantitatively explained by taking into account the effects of spin-spin correlation. With the electron doping introduced by Ge substitution, the diamagnetic insulating parent compound FeGa3 becomes a paramagnetic metal as early as at y=0.01, and turns into a weakly ferromagnetic metal around the quantum critical point y=0.15. Within the ferromagnetic regime of FeGa3-y Ge y , the magnetic properties are of a weakly itinerant ferromagnetic nature, located in the intermediate regime between the localized and the itinerant dominance. Our analysis implies a potential universality for all itinerant-electron ferromagnets.}, } @article {pmid29531068, year = {2018}, author = {Tong, T and Chen, S and Wang, L and Tang, Y and Ryu, JY and Jiang, S and Wu, X and Chen, C and Luo, J and Deng, Z and Li, Z and Lee, SY and Chen, S}, title = {Occurrence, evolution, and functions of DNA phosphorothioate epigenetics in bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2988-E2996}, pmid = {29531068}, issn = {1091-6490}, mesh = {DNA, Bacterial/chemistry/*genetics/metabolism ; *Epigenesis, Genetic ; Epigenomics ; *Evolution, Molecular ; *Gene Expression Regulation, Bacterial ; *Genes, Bacterial ; Genome, Bacterial ; Metabolomics ; Phosphates/*chemistry ; Phylogeny ; Pseudomonas fluorescens/*genetics/growth & development/metabolism ; Transcription, Genetic ; Transcriptome ; }, abstract = {The chemical diversity of physiological DNA modifications has expanded with the identification of phosphorothioate (PT) modification in which the nonbridging oxygen in the sugar-phosphate backbone of DNA is replaced by sulfur. Together with DndFGH as cognate restriction enzymes, DNA PT modification, which is catalyzed by the DndABCDE proteins, functions as a bacterial restriction-modification (R-M) system that protects cells against invading foreign DNA. However, the occurrence of dnd systems across a large number of bacterial genomes and their functions other than R-M are poorly understood. Here, a genomic survey revealed the prevalence of bacterial dnd systems: 1,349 bacterial dnd systems were observed to occur sporadically across diverse phylogenetic groups, and nearly half of these occur in the form of a solitary dndBCDE gene cluster that lacks the dndFGH restriction counterparts. A phylogenetic analysis of 734 complete PT R-M pairs revealed the coevolution of M and R components, despite the observation that several PT R-M pairs appeared to be assembled from M and R parts acquired from distantly related organisms. Concurrent epigenomic analysis, transcriptome analysis, and metabolome characterization showed that a solitary PT modification contributed to the overall cellular redox state, the loss of which perturbed the cellular redox balance and induced Pseudomonas fluorescens to reconfigure its metabolism to fend off oxidative stress. An in vitro transcriptional assay revealed altered transcriptional efficiency in the presence of PT DNA modification, implicating its function in epigenetic regulation. These data suggest the versatility of PT in addition to its involvement in R-M protection.}, } @article {pmid29531067, year = {2018}, author = {Raynes, Y and Wylie, CS and Sniegowski, PD and Weinreich, DM}, title = {Sign of selection on mutation rate modifiers depends on population size.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3422-3427}, pmid = {29531067}, issn = {1091-6490}, mesh = {*Evolution, Molecular ; Genetic Drift ; Models, Genetic ; *Mutation ; *Mutation Rate ; *Population Density ; Saccharomyces cerevisiae/*genetics ; Saccharomyces cerevisiae Proteins/*genetics ; *Selection, Genetic ; }, abstract = {The influence of population size (N) on natural selection acting on alleles that affect fitness has been understood for almost a century. As N declines, genetic drift overwhelms selection and alleles with direct fitness effects are rendered neutral. Often, however, alleles experience so-called indirect selection, meaning they affect not the fitness of an individual but the fitness distribution of its offspring. Some of the best-studied examples of indirect selection include alleles that modify aspects of the genetic system such as recombination and mutation rates. Here, we use analytics, simulations, and experimental populations of Saccharomyces cerevisiae to examine the influence of N on indirect selection acting on alleles that increase the genomic mutation rate (mutators). Mutators experience indirect selection via genomic associations with beneficial and deleterious mutations they generate. We show that, as N declines, indirect selection driven by linked beneficial mutations is overpowered by drift before drift can neutralize the cost of the deleterious load. As a result, mutators transition from being favored by indirect selection in large populations to being disfavored as N declines. This surprising phenomenon of sign inversion in selective effect demonstrates that indirect selection on mutators exhibits a profound and qualitatively distinct dependence on N.}, } @article {pmid29531066, year = {2018}, author = {LeClere, S and Wu, C and Westra, P and Sammons, RD}, title = {Cross-resistance to dicamba, 2,4-D, and fluroxypyr in Kochia scoparia is endowed by a mutation in an AUX/IAA gene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2911-E2920}, pmid = {29531066}, issn = {1091-6490}, mesh = {2,4-Dichlorophenoxyacetic Acid/pharmacology ; Acetates/pharmacology ; Arabidopsis/genetics ; Bassia scoparia/drug effects/growth & development/*physiology ; Dicamba/*pharmacology ; Herbicide Resistance/*genetics ; Herbicides/*pharmacology ; Indoleacetic Acids/pharmacology ; *Mutation ; Plant Proteins/*genetics ; Plant Weeds ; Pyridines/pharmacology ; }, abstract = {The understanding and mitigation of the appearance of herbicide-resistant weeds have come to the forefront of study in the past decade, as the number of weed species that are resistant to one or more herbicide modes of action is on the increase. Historically, weed resistance to auxin herbicides has been rare, but examples, such as Kochia scoparia L. Schrad (kochia), have appeared, posing a challenge to conventional agricultural practices. Reports of dicamba-resistant kochia populations began in the early 1990s in areas where auxin herbicides were heavily utilized for weed control in corn and wheat cropping systems, and some biotypes are resistant to other auxin herbicides as well. We have further characterized the auxin responses of one previously reported dicamba-resistant biotype isolated from western Nebraska and found that it is additionally cross-resistant to other auxin herbicides, including 2,4-dichlorophenoxyacetic acid (2,4-D) and fluroxypyr. We have utilized transcriptome sequencing and comparison to identify a 2-nt base change in this biotype, which results in a glycine to asparagine amino acid change within a highly conserved region of an AUX/indole-3-acetic acid (IAA) protein, KsIAA16. Through yeast two-hybrid analysis, characterization of F2 segregation, and heterologous expression and characterization of the gene in Arabidopsis thaliana, we show that that the single dominant KsIAA16R resistance allele is the causal basis for dicamba resistance in this population. Furthermore, we report the development of a molecular marker to identify this allele in populations and facilitate inheritance studies. We also report that the resistance allele confers a fitness penalty in greenhouse studies.}, } @article {pmid29531065, year = {2018}, author = {Gardella, C and Marre, O and Mora, T}, title = {Blindfold learning of an accurate neural metric.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3267-3272}, pmid = {29531065}, issn = {1091-6490}, support = {U01 NS090501/NS/NINDS NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; *Algorithms ; Brain/*physiology ; Humans ; Learning/*physiology ; *Models, Neurological ; Nerve Net/*physiology ; Neurons/*physiology ; }, abstract = {The brain has no direct access to physical stimuli but only to the spiking activity evoked in sensory organs. It is unclear how the brain can learn representations of the stimuli based on those noisy, correlated responses alone. Here we show how to build an accurate distance map of responses solely from the structure of the population activity of retinal ganglion cells. We introduce the Temporal Restricted Boltzmann Machine to learn the spatiotemporal structure of the population activity and use this model to define a distance between spike trains. We show that this metric outperforms existing neural distances at discriminating pairs of stimuli that are barely distinguishable. The proposed method provides a generic and biologically plausible way to learn to associate similar stimuli based on their spiking responses, without any other knowledge of these stimuli.}, } @article {pmid29531064, year = {2018}, author = {Angeles-Albores, D and Puckett Robinson, C and Williams, BA and Wold, BJ and Sternberg, PW}, title = {Reconstructing a metazoan genetic pathway with transcriptome-wide epistasis measurements.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2930-E2939}, pmid = {29531064}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*genetics/growth & development ; Caenorhabditis elegans Proteins/*genetics ; *Epistasis, Genetic ; *Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing/*methods ; *Transcriptome ; }, abstract = {RNA-sequencing (RNA-seq) is commonly used to identify genetic modules that respond to perturbations. In single cells, transcriptomes have been used as phenotypes, but this concept has not been applied to whole-organism RNA-seq. Also, quantifying and interpreting epistatic effects using expression profiles remains a challenge. We developed a single coefficient to quantify transcriptome-wide epistasis that reflects the underlying interactions and which can be interpreted intuitively. To demonstrate our approach, we sequenced four single and two double mutants of Caenorhabditis elegans From these mutants, we reconstructed the known hypoxia pathway. In addition, we uncovered a class of 56 genes with HIF-1-dependent expression that have opposite changes in expression in mutants of two genes that cooperate to negatively regulate HIF-1 abundance; however, the double mutant of these genes exhibits suppression epistasis. This class violates the classical model of HIF-1 regulation but can be explained by postulating a role of hydroxylated HIF-1 in transcriptional control.}, } @article {pmid29531063, year = {2018}, author = {van Ginkel, J and Filius, M and Szczepaniak, M and Tulinski, P and Meyer, AS and Joo, C}, title = {Single-molecule peptide fingerprinting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3338-3343}, pmid = {29531063}, issn = {1091-6490}, mesh = {Endopeptidase Clp/chemistry/*metabolism ; Escherichia coli Proteins/chemistry/*metabolism ; Fluorescence ; Fluorescent Dyes/*chemistry ; Humans ; Microscopy, Fluorescence/*methods ; Peptide Fragments/*analysis ; Peptide Mapping/*methods ; Proteomics/*methods ; }, abstract = {Proteomic analyses provide essential information on molecular pathways of cellular systems and the state of a living organism. Mass spectrometry is currently the first choice for proteomic analysis. However, the requirement for a large amount of sample renders a small-scale proteomics study challenging. Here, we demonstrate a proof of concept of single-molecule FRET-based protein fingerprinting. We harnessed the AAA+ protease ClpXP to scan peptides. By using donor fluorophore-labeled ClpP, we sequentially read out FRET signals from acceptor-labeled amino acids of peptides. The repurposed ClpXP exhibits unidirectional processing with high processivity and has the potential to detect low-abundance proteins. Our technique is a promising approach for sequencing protein substrates using a small amount of sample.}, } @article {pmid29531062, year = {2018}, author = {Mondal, D and Warshel, A}, title = {EF-Tu and EF-G are activated by allosteric effects.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3386-3391}, pmid = {29531062}, issn = {1091-6490}, support = {R35 GM122472/GM/NIGMS NIH HHS/United States ; U19 CA105010/CA/NCI NIH HHS/United States ; }, mesh = {Allosteric Regulation ; Binding Sites ; Catalysis ; Catalytic Domain ; Guanosine Triphosphate/*metabolism ; Models, Molecular ; Mutation ; Peptide Elongation Factor G/chemistry/genetics/*metabolism ; Peptide Elongation Factor Tu/chemistry/genetics/*metabolism ; }, abstract = {Many cellular processes are controlled by GTPases, and gaining quantitative understanding of the activation of such processes has been a major challenge. In particular, it is crucial to obtain reliable free-energy surfaces for the relevant reaction paths both in solution and in GTPases active sites. Here, we revisit the energetics of the activation of EF-G and EF-Tu by the ribosome and explore the nature of the catalysis of the GTPase reaction. The comparison of EF-Tu to EF-G allows us to explore the impact of possible problems with the available structure of EF-Tu. Additionally, mutational effects are used for a careful validation of the emerging conclusions. It is found that the reaction may proceed by both a two-water mechanism and a one-water (GTP as a base) mechanism. However, in both cases, the activation involves a structural allosteric effect, which is likely to be a general-activation mechanism for all GTPases.}, } @article {pmid29531061, year = {2018}, author = {Gerow, A and Hu, Y and Boyd-Graber, J and Blei, DM and Evans, JA}, title = {Measuring discursive influence across scholarship.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3308-3313}, pmid = {29531061}, issn = {1091-6490}, abstract = {Assessing scholarly influence is critical for understanding the collective system of scholarship and the history of academic inquiry. Influence is multifaceted, and citations reveal only part of it. Citation counts exhibit preferential attachment and follow a rigid "news cycle" that can miss sustained and indirect forms of influence. Building on dynamic topic models that track distributional shifts in discourse over time, we introduce a variant that incorporates features, such as authorship, affiliation, and publication venue, to assess how these contexts interact with content to shape future scholarship. We perform in-depth analyses on collections of physics research (500,000 abstracts; 102 years) and scholarship generally (JSTOR repository: 2 million full-text articles; 130 years). Our measure of document influence helps predict citations and shows how outcomes, such as winning a Nobel Prize or affiliation with a highly ranked institution, boost influence. Analysis of citations alongside discursive influence reveals that citations tend to credit authors who persist in their fields over time and discount credit for works that are influential over many topics or are "ahead of their time." In this way, our measures provide a way to acknowledge diverse contributions that take longer and travel farther to achieve scholarly appreciation, enabling us to correct citation biases and enhance sensitivity to the full spectrum of scholarly impact.}, } @article {pmid29531060, year = {2018}, author = {Patil, P and Parmigiani, G}, title = {Training replicable predictors in multiple studies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2578-2583}, pmid = {29531060}, issn = {1091-6490}, support = {P30 CA006516/CA/NCI NIH HHS/United States ; T32 CA009337/CA/NCI NIH HHS/United States ; }, mesh = {Biomedical Research/*methods/*standards ; Computer Simulation ; Databases, Factual ; Female ; Humans ; *Machine Learning ; Ovarian Neoplasms/diagnosis/mortality ; Prognosis ; Reproducibility of Results ; }, abstract = {This article considers replicability of the performance of predictors across studies. We suggest a general approach to investigating this issue, based on ensembles of prediction models trained on different studies. We quantify how the common practice of training on a single study accounts in part for the observed challenges in replicability of prediction performance. We also investigate whether ensembles of predictors trained on multiple studies can be combined, using unique criteria, to design robust ensemble learners trained upfront to incorporate replicability into different contexts and populations.}, } @article {pmid29531059, year = {2018}, author = {Lapinaite, A and Doudna, JA and Cate, JHD}, title = {Programmable RNA recognition using a CRISPR-associated Argonaute.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3368-3373}, pmid = {29531059}, issn = {1091-6490}, support = {R01 GM065050/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Argonaute Proteins/*chemistry/genetics/metabolism ; Bacteria/*genetics ; *CRISPR-Cas Systems ; Models, Biological ; RNA, Bacterial/*chemistry/genetics/metabolism ; RNA, Guide/*chemistry/genetics/metabolism ; }, abstract = {Argonaute proteins (Agos) are present in all domains of life. Although the physiological function of eukaryotic Agos in regulating gene expression is well documented, the biological roles of many of their prokaryotic counterparts remain enigmatic. In some bacteria, Agos are associated with CRISPR (clustered regularly interspaced short palindromic repeats) loci and use noncanonical 5'-hydroxylated guide RNAs (gRNAs) for nucleic acid targeting. Here we show that using 5-bromo-2'-deoxyuridine (BrdU) as the 5' nucleotide of gRNAs stabilizes in vitro reconstituted CRISPR-associated Marinitoga piezophila Argonaute-gRNA complexes (MpAgo RNPs) and significantly improves their specificity and affinity for RNA targets. Using reconstituted MpAgo RNPs with 5'-BrdU-modified gRNAs, we mapped the seed region of the gRNA and identified the nucleotides of the gRNA that play the most significant role in targeting specificity. We also show that these MpAgo RNPs can be programmed to distinguish between substrates that differ by a single nucleotide, using permutations at the sixth and seventh positions in the gRNA. Using these specificity features, we employed MpAgo RNPs to detect specific adenosine-to-inosine-edited RNAs in a complex mixture. These findings broaden our mechanistic understanding of the interactions of Argonautes with guide and substrate RNAs, and demonstrate that MpAgo RNPs with 5'-BrdU-modified gRNAs can be used as a highly specific RNA-targeting platform to probe RNA biology.}, } @article {pmid29531058, year = {2018}, author = {Kumar, J and Eraña, H and López-Martínez, E and Claes, N and Martín, VF and Solís, DM and Bals, S and Cortajarena, AL and Castilla, J and Liz-Marzán, LM}, title = {Detection of amyloid fibrils in Parkinson's disease using plasmonic chirality.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3225-3230}, pmid = {29531058}, issn = {1091-6490}, mesh = {Aged ; Amyloid/*analysis/*chemistry/ultrastructure ; Brain/pathology ; Circular Dichroism ; Cryoelectron Microscopy/methods ; Electron Microscope Tomography/methods ; Female ; Gold/chemistry ; Humans ; Lewy Bodies/pathology ; Nanotubes/*chemistry ; Parkinson Disease/*pathology ; Prions/analysis/genetics ; Surface Plasmon Resonance ; alpha-Synuclein/*chemistry/genetics ; }, abstract = {Amyloid fibrils, which are closely associated with various neurodegenerative diseases, are the final products in many protein aggregation pathways. The identification of fibrils at low concentration is, therefore, pivotal in disease diagnosis and development of therapeutic strategies. We report a methodology for the specific identification of amyloid fibrils using chiroptical effects in plasmonic nanoparticles. The formation of amyloid fibrils based on α-synuclein was probed using gold nanorods, which showed no apparent interaction with monomeric proteins but effective adsorption onto fibril structures via noncovalent interactions. The amyloid structure drives a helical nanorod arrangement, resulting in intense optical activity at the surface plasmon resonance wavelengths. This sensing technique was successfully applied to human brain homogenates of patients affected by Parkinson's disease, wherein protein fibrils related to the disease were identified through chiral signals from Au nanorods in the visible and near IR, whereas healthy brain samples did not exhibit any meaningful optical activity. The technique was additionally extended to the specific detection of infectious amyloids formed by prion proteins, thereby confirming the wide potential of the technique. The intense chiral response driven by strong dipolar coupling in helical Au nanorod arrangements allowed us to detect amyloid fibrils down to nanomolar concentrations.}, } @article {pmid29531057, year = {2018}, author = {Tan, IL and Wojcinski, A and Rallapalli, H and Lao, Z and Sanghrajka, RM and Stephen, D and Volkova, E and Korshunov, A and Remke, M and Taylor, MD and Turnbull, DH and Joyner, AL}, title = {Lateral cerebellum is preferentially sensitive to high sonic hedgehog signaling and medulloblastoma formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3392-3397}, pmid = {29531057}, issn = {1091-6490}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA192176/CA/NCI NIH HHS/United States ; R37 MH085726/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Animals ; Cell Differentiation ; Cerebellar Neoplasms/genetics/metabolism/*pathology ; Cerebellum/metabolism/*pathology ; Hedgehog Proteins/genetics/*metabolism ; Humans ; Infant ; Medulloblastoma/genetics/metabolism/*pathology ; Mice ; Patched-1 Receptor/genetics/*metabolism ; Signal Transduction ; Smoothened Receptor/genetics/*metabolism ; Transcriptome ; }, abstract = {The main cell of origin of the Sonic hedgehog (SHH) subgroup of medulloblastoma (MB) is granule cell precursors (GCPs), a SHH-dependent transient amplifying population in the developing cerebellum. SHH-MBs can be further subdivided based on molecular and clinical parameters, as well as location because SHH-MBs occur preferentially in the lateral cerebellum (hemispheres). Our analysis of adult patient data suggests that tumors with Smoothened (SMO) mutations form more specifically in the hemispheres than those with Patched 1 (PTCH1) mutations. Using sporadic mouse models of SHH-MB with the two mutations commonly seen in adult MB, constitutive activation of Smo (SmoM2) or loss-of-Ptch1, we found that regardless of timing of induction or type of mutation, tumors developed primarily in the hemispheres, with SmoM2-mutants indeed showing a stronger specificity. We further uncovered that GCPs in the hemispheres are more susceptible to high-level SHH signaling compared with GCPs in the medial cerebellum (vermis), as more SmoM2 or Ptch1-mutant hemisphere cells remain undifferentiated and show increased tumorigenicity when transplanted. Finally, we identified location-specific GCP gene-expression profiles, and found that deletion of the genes most highly expressed in the hemispheres (Nr2f2) or vermis (Engrailed1) showed opposing effects on GCP differentiation. Our studies thus provide insights into intrinsic differences within GCPs that impact on SHH-MB progression.}, } @article {pmid29531056, year = {2018}, author = {Hirano, A and Hsu, PK and Zhang, L and Xing, L and McMahon, T and Yamazaki, M and Ptáček, LJ and Fu, YH}, title = {DEC2 modulates orexin expression and regulates sleep.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3434-3439}, pmid = {29531056}, issn = {1091-6490}, support = {P30 DK063720/DK/NIDDK NIH HHS/United States ; R01 HL059596/HL/NHLBI NIH HHS/United States ; R01 NS072360/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics/*metabolism ; *Gene Expression Regulation ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; *Mutation ; Orexins/*genetics/metabolism ; *Promoter Regions, Genetic ; Sleep/*physiology ; }, abstract = {Adequate sleep is essential for physical and mental health. We previously identified a missense mutation in the human DEC2 gene (BHLHE41) leading to the familial natural short sleep behavioral trait. DEC2 is a transcription factor regulating the circadian clock in mammals, although its role in sleep regulation has been unclear. Here we report that prepro-orexin, also known as hypocretin (Hcrt), gene expression is increased in the mouse model expressing the mutant hDEC2 transgene (hDEC2-P384R). Prepro-orexin encodes a precursor protein of a neuropeptide producing orexin A and B (hcrt1 and hcrt2), which is enriched in the hypothalamus and regulates maintenance of arousal. In cell culture, DEC2 suppressed prepro-orexin promoter-luc (ore-luc) expression through cis-acting E-box elements. The mutant DEC2 has less repressor activity than WT-DEC2, resulting in increased orexin expression. DEC2-binding affinity for the prepro-orexin gene promoter is decreased by the P384R mutation, likely due to weakened interaction with other transcription factors. In vivo, the decreased immobility time of the mutant transgenic mice is attenuated by an orexin receptor antagonist. Our results suggested that DEC2 regulates sleep/wake duration, at least in part, by modulating the neuropeptide hormone orexin.}, } @article {pmid29531055, year = {2018}, author = {Banerjee, R and Yoder, JB and Yue, DT and Amzel, LM and Tomaselli, GF and Gabelli, SB and Ben-Johny, M}, title = {Bilobal architecture is a requirement for calmodulin signaling to CaV1.3 channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3026-E3035}, pmid = {29531055}, issn = {1091-6490}, support = {R01 HL128743/HL/NHLBI NIH HHS/United States ; R01 MH065531/MH/NIMH NIH HHS/United States ; T32 GM008403/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Calcium/*metabolism ; Calcium Channels/chemistry/*metabolism ; *Calcium Signaling ; Calmodulin/chemistry/*metabolism ; Humans ; Ion Channel Gating/*physiology ; Models, Molecular ; Protein Binding ; Protein Conformation ; Rats ; Sequence Homology ; Signal Transduction ; }, abstract = {Calmodulin (CaM) regulation of voltage-gated calcium (CaV) channels is a powerful Ca2+ feedback mechanism that adjusts Ca2+ influx, affording rich mechanistic insights into Ca2+ decoding. CaM possesses a dual-lobed architecture, a salient feature of the myriad Ca2+-sensing proteins, where two homologous lobes that recognize similar targets hint at redundant signaling mechanisms. Here, by tethering CaM lobes, we demonstrate that bilobal architecture is obligatory for signaling to CaV channels. With one lobe bound, CaV carboxy tail rearranges itself, resulting in a preinhibited configuration precluded from Ca2+ feedback. Reconstitution of two lobes, even as separate molecules, relieves preinhibition and restores Ca2+ feedback. CaV channels thus detect the coincident binding of two Ca2+-free lobes to promote channel opening, a molecular implementation of a logical NOR operation that processes spatiotemporal Ca2+ signals bifurcated by CaM lobes. Overall, a unified scheme of CaV channel regulation by CaM now emerges, and our findings highlight the versatility of CaM to perform exquisite Ca2+ computations.}, } @article {pmid29531054, year = {2018}, author = {Radeloff, VC and Helmers, DP and Kramer, HA and Mockrin, MH and Alexandre, PM and Bar-Massada, A and Butsic, V and Hawbaker, TJ and Martinuzzi, S and Syphard, AD and Stewart, SI}, title = {Rapid growth of the US wildland-urban interface raises wildfire risk.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3314-3319}, pmid = {29531054}, issn = {1091-6490}, mesh = {*Conservation of Natural Resources ; *Ecosystem ; *Housing ; Humans ; Risk Factors ; United States ; *Urbanization ; Wildfires/*statistics & numerical data ; }, abstract = {The wildland-urban interface (WUI) is the area where houses and wildland vegetation meet or intermingle, and where wildfire problems are most pronounced. Here we report that the WUI in the United States grew rapidly from 1990 to 2010 in terms of both number of new houses (from 30.8 to 43.4 million; 41% growth) and land area (from 581,000 to 770,000 km2; 33% growth), making it the fastest-growing land use type in the conterminous United States. The vast majority of new WUI areas were the result of new housing (97%), not related to an increase in wildland vegetation. Within the perimeter of recent wildfires (1990-2015), there were 286,000 houses in 2010, compared with 177,000 in 1990. Furthermore, WUI growth often results in more wildfire ignitions, putting more lives and houses at risk. Wildfire problems will not abate if recent housing growth trends continue.}, } @article {pmid29531053, year = {2018}, author = {Valdiosera, C and Günther, T and Vera-Rodríguez, JC and Ureña, I and Iriarte, E and Rodríguez-Varela, R and Simões, LG and Martínez-Sánchez, RM and Svensson, EM and Malmström, H and Rodríguez, L and Bermúdez de Castro, JM and Carbonell, E and Alday, A and Hernández Vera, JA and Götherström, A and Carretero, JM and Arsuaga, JL and Smith, CI and Jakobsson, M}, title = {Four millennia of Iberian biomolecular prehistory illustrate the impact of prehistoric migrations at the far end of Eurasia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3428-3433}, pmid = {29531053}, issn = {1091-6490}, mesh = {Archaeology ; DNA/*analysis/genetics ; Europe ; Farmers/*history ; Genetic Variation ; *Genetics, Population ; *Genome, Human ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; History, Ancient ; Human Migration/*history ; Humans ; }, abstract = {Population genomic studies of ancient human remains have shown how modern-day European population structure has been shaped by a number of prehistoric migrations. The Neolithization of Europe has been associated with large-scale migrations from Anatolia, which was followed by migrations of herders from the Pontic steppe at the onset of the Bronze Age. Southwestern Europe was one of the last parts of the continent reached by these migrations, and modern-day populations from this region show intriguing similarities to the initial Neolithic migrants. Partly due to climatic conditions that are unfavorable for DNA preservation, regional studies on the Mediterranean remain challenging. Here, we present genome-wide sequence data from 13 individuals combined with stable isotope analysis from the north and south of Iberia covering a four-millennial temporal transect (7,500-3,500 BP). Early Iberian farmers and Early Central European farmers exhibit significant genetic differences, suggesting two independent fronts of the Neolithic expansion. The first Neolithic migrants that arrived in Iberia had low levels of genetic diversity, potentially reflecting a small number of individuals; this diversity gradually increased over time from mixing with local hunter-gatherers and potential population expansion. The impact of post-Neolithic migrations on Iberia was much smaller than for the rest of the continent, showing little external influence from the Neolithic to the Bronze Age. Paleodietary reconstruction shows that these populations have a remarkable degree of dietary homogeneity across space and time, suggesting a strong reliance on terrestrial food resources despite changing culture and genetic make-up.}, } @article {pmid29531052, year = {2018}, author = {Aviram, HY and Pirchi, M and Mazal, H and Barak, Y and Riven, I and Haran, G}, title = {Direct observation of ultrafast large-scale dynamics of an enzyme under turnover conditions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3243-3248}, pmid = {29531052}, issn = {1091-6490}, support = {742637//European Research Council/International ; }, mesh = {Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Adenylate Kinase/*chemistry/genetics/*metabolism ; Binding Sites ; Escherichia coli Proteins/chemistry/genetics/metabolism ; Fluorescence Resonance Energy Transfer/*methods ; Point Mutation ; Protein Conformation ; Protein Domains ; }, abstract = {The functional cycle of many proteins involves large-scale motions of domains and subunits. The relation between conformational dynamics and the chemical steps of enzymes remains under debate. Here we show that in the presence of substrates, domain motions of an enzyme can take place on the microsecond time scale, yet exert influence on the much-slower chemical step. We study the domain closure reaction of the enzyme adenylate kinase from Escherichia coli while in action (i.e., under turnover conditions), using single-molecule FRET spectroscopy. We find that substrate binding increases dramatically domain closing and opening times, making them as short as ∼15 and ∼45 µs, respectively. These large-scale conformational dynamics are likely the fastest measured to date, and are ∼100-200 times faster than the enzymatic turnover rate. Some active-site mutants are shown to fully or partially prevent the substrate-induced increase in domain closure times, while at the same time they also reduce enzymatic activity, establishing a clear connection between the two phenomena, despite their disparate time scales. Based on these surprising observations, we propose a paradigm for the mode of action of enzymes, in which numerous cycles of conformational rearrangement are required to find a mutual orientation of substrates that is optimal for the chemical reaction.}, } @article {pmid29531051, year = {2018}, author = {Fanelli, D}, title = {Opinion: Is science really facing a reproducibility crisis, and do we need it to?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2628-2631}, pmid = {29531051}, issn = {1091-6490}, abstract = {Efforts to improve the reproducibility and integrity of science are typically justified by a narrative of crisis, according to which most published results are unreliable due to growing problems with research and publication practices. This article provides an overview of recent evidence suggesting that this narrative is mistaken, and argues that a narrative of epochal changes and empowerment of scientists would be more accurate, inspiring, and compelling.}, } @article {pmid29531050, year = {2018}, author = {Stodden, V and Seiler, J and Ma, Z}, title = {An empirical analysis of journal policy effectiveness for computational reproducibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2584-2589}, pmid = {29531050}, issn = {1091-6490}, abstract = {A key component of scientific communication is sufficient information for other researchers in the field to reproduce published findings. For computational and data-enabled research, this has often been interpreted to mean making available the raw data from which results were generated, the computer code that generated the findings, and any additional information needed such as workflows and input parameters. Many journals are revising author guidelines to include data and code availability. This work evaluates the effectiveness of journal policy that requires the data and code necessary for reproducibility be made available postpublication by the authors upon request. We assess the effectiveness of such a policy by (i) requesting data and code from authors and (ii) attempting replication of the published findings. We chose a random sample of 204 scientific papers published in the journal Science after the implementation of their policy in February 2011. We found that we were able to obtain artifacts from 44% of our sample and were able to reproduce the findings for 26%. We find this policy-author remission of data and code postpublication upon request-an improvement over no policy, but currently insufficient for reproducibility.}, } @article {pmid29531049, year = {2018}, author = {Dively, GP and Venugopal, PD and Bean, D and Whalen, J and Holmstrom, K and Kuhar, TP and Doughty, HB and Patton, T and Cissel, W and Hutchison, WD}, title = {Regional pest suppression associated with widespread Bt maize adoption benefits vegetable growers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3320-3325}, pmid = {29531049}, issn = {1091-6490}, mesh = {Animals ; Bacillus thuringiensis/*genetics ; *Crops, Agricultural ; Insecticide Resistance ; Insecticides/*pharmacology ; Moths/classification/*physiology ; *Pest Control, Biological ; Plant Diseases/genetics/parasitology/*prevention & control ; Plants, Genetically Modified/*growth & development ; Population Dynamics ; Zea mays/*growth & development/metabolism/parasitology ; }, abstract = {Transgenic crops containing the bacterium Bacillus thuringiensis (Bt) genes reduce pests and insecticide usage, promote biocontrol services, and economically benefit growers. Area-wide Bt adoption suppresses pests regionally, with declines expanding beyond the planted Bt crops into other non-Bt crop fields. However, the offsite benefits to growers of other crops from such regional suppression remain uncertain. With data spanning 1976-2016, we demonstrate that vegetable growers benefit via decreased crop damage and insecticide applications in relation to pest suppression in the Mid-Atlantic United States. We provide evidence for the regional suppression of Ostrinia nubilalis (Hübner), European corn borer, and Helicoverpa zea (Boddie), corn earworm, populations in association with widespread Bt maize adoption (1996-2016) and decreased economic levels for injury in vegetable crops [peppers (Capsicum annuum L.), green beans (Phaseolus vulgaris L.), and sweet corn (Zea mays L., convar. saccharata)] compared with the pre-Bt period (1976-1995). Moth populations of both species significantly declined in association with widespread Bt maize (field corn) adoption, even as increased temperatures buffered the population reduction. We show marked decreases in the number of recommended insecticidal applications, insecticides applied, and O. nubilalis damage in vegetable crops in association with widespread Bt maize adoption. These offsite benefits to vegetable growers in the agricultural landscape have not been previously documented, and the positive impacts identified here expand on the reported ecological effects of Bt adoption. Our results also underscore the need to account for offsite economic benefits of pest suppression, in addition to the direct economic benefits of Bt crops.}, } @article {pmid29531048, year = {2018}, author = {Seeman, T and Thomas, D and Merkin, SS and Moore, K and Watson, K and Karlamangla, A}, title = {The Great Recession worsened blood pressure and blood glucose levels in American adults.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3296-3301}, pmid = {29531048}, issn = {1091-6490}, support = {HHSN268201500003C/HL/NHLBI NIH HHS/United States ; N01HC95160/HL/NHLBI NIH HHS/United States ; N01HC95163/HL/NHLBI NIH HHS/United States ; UL1 TR001079/TR/NCATS NIH HHS/United States ; N01HC95169/HL/NHLBI NIH HHS/United States ; N01HC95164/HL/NHLBI NIH HHS/United States ; N01HC95162/HL/NHLBI NIH HHS/United States ; N01HC95168/HL/NHLBI NIH HHS/United States ; N01HC95165/HL/NHLBI NIH HHS/United States ; N01HC95159/HL/NHLBI NIH HHS/United States ; N01HC95161/HL/NHLBI NIH HHS/United States ; UL1 TR001420/TR/NCATS NIH HHS/United States ; R21 AG046589/AG/NIA NIH HHS/United States ; N01HC95167/HL/NHLBI NIH HHS/United States ; UL1 TR000040/TR/NCATS NIH HHS/United States ; N01HC95166/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Blood Glucose/*analysis ; *Blood Pressure ; Cardiovascular Diseases/*economics/epidemiology ; Diabetes Complications/*economics/epidemiology ; Economic Recession/*statistics & numerical data ; Employment/*psychology ; Female ; *Health Behavior ; Humans ; Income ; Male ; Middle Aged ; Prospective Studies ; United States/epidemiology ; }, abstract = {Longitudinal, individual-specific data from the Multi-Ethnic Study of Atherosclerosis (MESA) provide support for the hypothesis that the 2008 to 2010 Great Recession (GR) negatively impacted the health of US adults. Results further advance understanding of the relationship by (i) illuminating hypothesized greater negative impacts in population subgroups exposed to more severe impacts of the GR and (ii) explicitly controlling for confounding by individual differences in age-related changes in health over time. Analyses overcome limitations of prior work by (i) employing individual-level data that avoid concerns about ecological fallacy associated with prior reliance on group-level data, (ii) using four waves of data before the GR to estimate and control for underlying individual-level age-related trends, (iii) focusing on objective, temporally appropriate health outcomes rather than mortality, and (iv) leveraging a diverse cohort to investigate subgroup differences in the GR's impact. Innovative individual fixed-effects modeling controlling for individual-level age-related trajectories yielded substantively important insights: (i) significant elevations post-GR for blood pressure and fasting glucose, especially among those on medication pre-GR, and (ii) reductions in prevalence and intensity of medication use post-GR. Important differences in the effects of the GR are seen across subgroups, with larger effects among younger adults (who are likely still in the labor force) and older homeowners (whose declining home wealth likely reduced financial security, with less scope for recouping losses during their lifetime); least affected were older adults without a college degree (whose greater reliance on Medicare and Social Security likely provided more protection from the recession).}, } @article {pmid29531047, year = {2018}, author = {Del Prado, A and Franco-Echevarría, E and González, B and Blanco, L and Salas, M and de Vega, M}, title = {Noncatalytic aspartate at the exonuclease domain of proofreading DNA polymerases regulates both degradative and synthetic activities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2921-E2929}, pmid = {29531047}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Aspartic Acid/*genetics ; Bacillus Phages/*enzymology/genetics ; *DNA Repair ; *DNA Replication ; DNA-Directed DNA Polymerase/genetics/*metabolism ; Exodeoxyribonucleases/genetics/*metabolism ; Mutagenesis, Site-Directed ; *Mutation ; Sequence Homology ; }, abstract = {Most replicative DNA polymerases (DNAPs) are endowed with a 3'-5' exonuclease activity to proofread the polymerization errors, governed by four universally conserved aspartate residues belonging to the Exo I, Exo II, and Exo III motifs. These residues coordinate the two metal ions responsible for the hydrolysis of the last phosphodiester bond of the primer strand. Structural alignment of the conserved exonuclease domain of DNAPs from families A, B, and C has allowed us to identify an additional and invariant aspartate, located between motifs Exo II and Exo III. The importance of this aspartate has been assessed by site-directed mutagenesis at the corresponding Asp121 of the family B ϕ29 DNAP. Substitution of this residue by either glutamate or alanine severely impaired the catalytic efficiency of the 3'-5' exonuclease activity, both on ssDNA and dsDNA. The polymerization activity of these mutants was also affected due to a defective translocation following nucleotide incorporation. Alanine substitution for the homologous Asp90 in family A T7 DNAP showed essentially the same phenotype as ϕ29 DNAP mutant D121A. This functional conservation, together with a close inspection of ϕ29 DNAP/DNA complexes, led us to conclude a pivotal role for this aspartate in orchestrating the network of interactions required during internal proofreading of misinserted nucleotides.}, } @article {pmid29531046, year = {2018}, author = {}, title = {Correction for Kudalkar et al., From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2899}, doi = {10.1073/pnas.1803199115}, pmid = {29531046}, issn = {1091-6490}, support = {T32 GM007223/GM/NIGMS NIH HHS/United States ; }, } @article {pmid29531045, year = {2018}, author = {Hegyi, B and Bossuyt, J and Griffiths, LG and Shimkunas, R and Coulibaly, Z and Jian, Z and Grimsrud, KN and Sondergaard, CS and Ginsburg, KS and Chiamvimonvat, N and Belardinelli, L and Varró, A and Papp, JG and Pollesello, P and Levijoki, J and Izu, LT and Boyd, WD and Bányász, T and Bers, DM and Chen-Izu, Y}, title = {Complex electrophysiological remodeling in postinfarction ischemic heart failure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3036-E3044}, pmid = {29531045}, issn = {1091-6490}, support = {R01 HL090880/HL/NHLBI NIH HHS/United States ; P01 HL080101/HL/NHLBI NIH HHS/United States ; R01 HL085727/HL/NHLBI NIH HHS/United States ; R01 HL092097/HL/NHLBI NIH HHS/United States ; R01 HL123526/HL/NHLBI NIH HHS/United States ; I01 CX001490/CX/CSRD VA/United States ; R01 HL030077/HL/NHLBI NIH HHS/United States ; R01 HL137228/HL/NHLBI NIH HHS/United States ; I01 BX000576/BX/BLRD VA/United States ; R01 HL085844/HL/NHLBI NIH HHS/United States ; R01 HL105242/HL/NHLBI NIH HHS/United States ; }, mesh = {Action Potentials/*physiology ; Animals ; Arrhythmias, Cardiac/*physiopathology ; Calcium/*metabolism ; Cells, Cultured ; *Electrophysiological Phenomena ; Heart Failure/*physiopathology ; Myocardial Infarction/*physiopathology ; Myocytes, Cardiac/cytology/*physiology ; Swine ; }, abstract = {Heart failure (HF) following myocardial infarction (MI) is associated with high incidence of cardiac arrhythmias. Development of therapeutic strategy requires detailed understanding of electrophysiological remodeling. However, changes of ionic currents in ischemic HF remain incompletely understood, especially in translational large-animal models. Here, we systematically measure the major ionic currents in ventricular myocytes from the infarct border and remote zones in a porcine model of post-MI HF. We recorded eight ionic currents during the cell's action potential (AP) under physiologically relevant conditions using selfAP-clamp sequential dissection. Compared with healthy controls, HF-remote zone myocytes exhibited increased late Na+ current, Ca2+-activated K+ current, Ca2+-activated Cl- current, decreased rapid delayed rectifier K+ current, and altered Na+/Ca2+ exchange current profile. In HF-border zone myocytes, the above changes also occurred but with additional decrease of L-type Ca2+ current, decrease of inward rectifier K+ current, and Ca2+ release-dependent delayed after-depolarizations. Our data reveal that the changes in any individual current are relatively small, but the integrated impacts shift the balance between the inward and outward currents to shorten AP in the border zone but prolong AP in the remote zone. This differential remodeling in post-MI HF increases the inhomogeneity of AP repolarization, which may enhance the arrhythmogenic substrate. Our comprehensive findings provide a mechanistic framework for understanding why single-channel blockers may fail to suppress arrhythmias, and highlight the need to consider the rich tableau and integration of many ionic currents in designing therapeutic strategies for treating arrhythmias in HF.}, } @article {pmid29531044, year = {2018}, author = {}, title = {Retraction for Maisonneuve et al., Bacterial persistence by RNA endonucleases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2901}, doi = {10.1073/pnas.1803278115}, pmid = {29531044}, issn = {1091-6490}, } @article {pmid29531043, year = {2018}, author = {Zhang, Y and Liu, W and Li, R and Gu, J and Wu, P and Peng, C and Ma, J and Wu, L and Yu, Y and Huang, Y}, title = {Structural insights into the sequence-specific recognition of Piwi by Drosophila Papi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3374-3379}, pmid = {29531043}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Animals ; Argonaute Proteins/*chemistry/genetics/metabolism ; Carrier Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Drosophila Proteins/*chemistry/genetics/metabolism ; Drosophila melanogaster/genetics/growth & development/*metabolism ; Female ; *Infertility ; RNA, Fungal/*chemistry/genetics/metabolism ; Sequence Homology ; }, abstract = {The Tudor domain-containing (Tdrd) family proteins play a critical role in transposon silencing in animal gonads by recognizing the symmetrically dimethylated arginine (sDMA) on the (G/A)R motif of the N-terminal of PIWI family proteins via the eTud domains. Papi, also known as "Tdrd2," is involved in Zucchini-mediated PIWI-interacting RNA (piRNA) 3'-end maturation. Intriguingly, a recent study showed that, in papi mutant flies, only Piwi-bound piRNAs increased in length, and not Ago3-bound or Aub-bound piRNAs. However, the molecular and structural basis of the Papi-Piwi complex is still not fully understood, which limits mechanistic understanding of the function of Papi in piRNA biogenesis. In the present study, we determined the crystal structures of Papi-eTud in the apo form and in complex with a peptide containing unmethylated or dimethylated R10 residues. Structural and biochemical analysis showed that the Papi interaction region on the Drosophila Piwi contains an RGRRR motif (R7-R11) distinct from the consensus (G/A)R motif recognized by canonical eTud. Mass spectrometry results indicated that Piwi is the major binding partner of Papi in vivo. The papi mutant flies suffered from both fertility and transposon-silencing defects, supporting the important role conferred to Papi in piRNA 3' processing through direct interaction with Piwi proteins.}, } @article {pmid29531042, year = {2018}, author = {Wada, H and Yasmin, N and Kakugawa, K and Ohno-Oishi, M and Nieke, S and Miyamoto, C and Muroi, S and Taniuchi, I}, title = {Requirement for intron structures in activating the Cd8a locus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3440-3445}, pmid = {29531042}, issn = {1091-6490}, mesh = {Animals ; CD4 Antigens/genetics/*metabolism ; CD4-Positive T-Lymphocytes/cytology/*metabolism ; CD8 Antigens/genetics/*metabolism ; CD8-Positive T-Lymphocytes/cytology/*metabolism ; Cell Differentiation ; Cells, Cultured ; *Introns ; Mice ; RNA Splicing ; T-Lymphocytes, Cytotoxic/*metabolism ; Thymocytes/cytology/*metabolism ; }, abstract = {During differentiation of CD4+CD8+ double-positive (DP) thymocytes into the CD4-CD8+ single-positive (CD8SP) thymocytes committed to the cytotoxic T cell lineage, Cd8a transcription is temporally terminated after positive selection and is subsequently reinitiated, a process known as coreceptor reversal. Despite the identification of a transcriptional enhancer in the Cd8a gene that directs reporter transgene expression specifically in CD8SP thymocytes, the molecular mechanisms controlling reactivation of the Cd8a gene are not fully understood. Here, we show that, after positive selection, hCD2 reporter expression from the Cd8a locus, which was generated by insertion of hCD2 cDNA into the first exon of the Cd8a gene, requires the incorporation of intron sequences into the hCD2 transcript. The presence of polyadenylation signals after hCD2 cDNA inhibited hCD2 expression in mature CD8+ T cells, whereas hCD2 expression in DP thymocytes recapitulated the Cd8a expression. Incorporation of the endogenous short intron structure and heterologous intron structure of the Cd4 locus restored hCD2 expression in mature CD8+ T cells in a variegated manner. Interestingly, stage-specific DNA demethylation was impaired in Cd8a reporter alleles that failed to express hCD2 in CD8+ T cells, and intron sequences lacking RNA splicing signals still restored hCD2 expression. These observations indicate that "intron-mediated enhancement" is involved in a stage-specific reactivation of the Cd8a locus harboring hCD2 cDNA. However, the Cd8a gene was transcribed in mature CD8+ T cells, albeit at a lower level, from a mutant Cd8a locus lacking intron structures, suggesting that protein-coding sequences in transcripts affect sensitivity to intron-mediated enhancement.}, } @article {pmid29531041, year = {2018}, author = {Diehl, A and Roske, Y and Ball, L and Chowdhury, A and Hiller, M and Molière, N and Kramer, R and Stöppler, D and Worth, CL and Schlegel, B and Leidert, M and Cremer, N and Erdmann, N and Lopez, D and Stephanowitz, H and Krause, E and van Rossum, BJ and Schmieder, P and Heinemann, U and Turgay, K and Akbey, Ü and Oschkinat, H}, title = {Structural changes of TasA in biofilm formation of Bacillus subtilis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3237-3242}, pmid = {29531041}, issn = {1091-6490}, mesh = {Bacillus subtilis/chemistry/*physiology ; Bacterial Proteins/*chemistry/metabolism ; Biofilms/*growth & development ; Calorimetry ; Crystallography, X-Ray ; Hydrogen-Ion Concentration ; Magnetic Resonance Spectroscopy ; Metalloendopeptidases/chemistry ; Microscopy, Electron ; Models, Molecular ; Molecular Weight ; Protein Conformation ; Structural Homology, Protein ; Ultracentrifugation ; }, abstract = {Microorganisms form surface-attached communities, termed biofilms, which can serve as protection against host immune reactions or antibiotics. Bacillus subtilis biofilms contain TasA as major proteinaceous component in addition to exopolysaccharides. In stark contrast to the initially unfolded biofilm proteins of other bacteria, TasA is a soluble, stably folded monomer, whose structure we have determined by X-ray crystallography. Subsequently, we characterized in vitro different oligomeric forms of TasA by NMR, EM, X-ray diffraction, and analytical ultracentrifugation (AUC) experiments. However, by magic-angle spinning (MAS) NMR on live biofilms, a swift structural change toward only one of these forms, consisting of homogeneous and protease-resistant, β-sheet-rich fibrils, was observed in vivo. Thereby, we characterize a structural change from a globular state to a fibrillar form in a functional prokaryotic system on the molecular level.}, } @article {pmid29531040, year = {2018}, author = {Veeramah, KR and Rott, A and Groß, M and van Dorp, L and López, S and Kirsanow, K and Sell, C and Blöcher, J and Wegmann, D and Link, V and Hofmanová, Z and Peters, J and Trautmann, B and Gairhos, A and Haberstroh, J and Päffgen, B and Hellenthal, G and Haas-Gebhard, B and Harbeck, M and Burger, J}, title = {Population genomic analysis of elongated skulls reveals extensive female-biased immigration in Early Medieval Bavaria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3494-3499}, pmid = {29531040}, issn = {1091-6490}, mesh = {Archaeology ; DNA, Ancient ; European Continental Ancestry Group/*genetics ; Female ; Genetic Variation ; *Genetics, Population ; *Genome, Human ; Genomics/*methods ; Germany ; Haplotypes ; History, Medieval ; *Human Migration ; Humans ; Phenotype ; Skull/anatomy & histology/*metabolism ; Whole Genome Sequencing ; }, abstract = {Modern European genetic structure demonstrates strong correlations with geography, while genetic analysis of prehistoric humans has indicated at least two major waves of immigration from outside the continent during periods of cultural change. However, population-level genome data that could shed light on the demographic processes occurring during the intervening periods have been absent. Therefore, we generated genomic data from 41 individuals dating mostly to the late 5th/early 6th century AD from present-day Bavaria in southern Germany, including 11 whole genomes (mean depth 5.56×). In addition we developed a capture array to sequence neutral regions spanning a total of 5 Mb and 486 functional polymorphic sites to high depth (mean 72×) in all individuals. Our data indicate that while men generally had ancestry that closely resembles modern northern and central Europeans, women exhibit a very high genetic heterogeneity; this includes signals of genetic ancestry ranging from western Europe to East Asia. Particularly striking are women with artificial skull deformations; the analysis of their collective genetic ancestry suggests an origin in southeastern Europe. In addition, functional variants indicate that they also differed in visible characteristics. This example of female-biased migration indicates that complex demographic processes during the Early Medieval period may have contributed in an unexpected way to shape the modern European genetic landscape. Examination of the panel of functional loci also revealed that many alleles associated with recent positive selection were already at modern-like frequencies in European populations ∼1,500 years ago.}, } @article {pmid29531039, year = {2018}, author = {}, title = {Correction for Dixon et al., Heterogeneity within the frontoparietal control network and its relationship to the default and dorsal attention networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3068}, doi = {10.1073/pnas.1803276115}, pmid = {29531039}, issn = {1091-6490}, } @article {pmid29531038, year = {2018}, author = {Nobori, T and Velásquez, AC and Wu, J and Kvitko, BH and Kremer, JM and Wang, Y and He, SY and Tsuda, K}, title = {Transcriptome landscape of a bacterial pathogen under plant immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3055-E3064}, pmid = {29531038}, issn = {1091-6490}, support = {R01 GM109928/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/genetics/*microbiology ; Bacterial Proteins/*genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; Gene Regulatory Networks ; Plant Diseases/immunology/*microbiology ; Plant Immunity/genetics/*immunology ; Plants, Genetically Modified/genetics/microbiology ; Pseudomonas syringae/*genetics/growth & development ; *Transcriptome ; }, abstract = {Plant pathogens can cause serious diseases that impact global agriculture. The plant innate immunity, when fully activated, can halt pathogen growth in plants. Despite extensive studies into the molecular and genetic bases of plant immunity against pathogens, the influence of plant immunity in global pathogen metabolism to restrict pathogen growth is poorly understood. Here, we developed RNA sequencing pipelines for analyzing bacterial transcriptomes in planta and determined high-resolution transcriptome patterns of the foliar bacterial pathogen Pseudomonas syringae in Arabidopsis thaliana with a total of 27 combinations of plant immunity mutants and bacterial strains. Bacterial transcriptomes were analyzed at 6 h post infection to capture early effects of plant immunity on bacterial processes and to avoid secondary effects caused by different bacterial population densities in planta We identified specific "immune-responsive" bacterial genes and processes, including those that are activated in susceptible plants and suppressed by plant immune activation. Expression patterns of immune-responsive bacterial genes at the early time point were tightly linked to later bacterial growth levels in different host genotypes. Moreover, we found that a bacterial iron acquisition pathway is commonly suppressed by multiple plant immune-signaling pathways. Overexpression of a P. syringae sigma factor gene involved in iron regulation and other processes partially countered bacterial growth restriction during the plant immune response triggered by AvrRpt2. Collectively, this study defines the effects of plant immunity on the transcriptome of a bacterial pathogen and sheds light on the enigmatic mechanisms of bacterial growth inhibition during the plant immune response.}, } @article {pmid29531037, year = {2018}, author = {Thévenin, C and Mouchet, M and Robert, A and Kerbiriou, C and Sarrazin, F}, title = {Reintroductions of birds and mammals involve evolutionarily distinct species at the regional scale.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3404-3409}, pmid = {29531037}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; *Biological Evolution ; Birds/*physiology ; Central America ; *Conservation of Natural Resources ; Europe ; Mammals/*physiology ; Phylogeny ; }, abstract = {Reintroductions offer a powerful tool for reversing the effects of species extirpation and have been increasingly used over recent decades. However, this species-centered conservation approach has been criticized for its strong biases toward charismatic birds and mammals. Here, we investigated whether reintroduced species can be representative of the phylogenetic diversity within these two groups at a continental scale (i.e., Europe, North and Central America). Using null models, we found that reintroduced birds and mammals of the two subcontinents tend to be more evolutionarily distinct than expected by chance, despite strong taxonomic biases leading to low values of phylogenetic diversity. While evolutionary considerations are unlikely to have explicitly driven the allocation of reintroduction efforts, our results illustrate an interest of reintroduction practitioners toward species with fewer close relatives. We discuss how this phylogenetic framework allows us to investigate the contribution of reintroductions to the conservation of biodiversity at multiple geographic scales. We argue that because reintroductions rely on a parochial approach of conservation, it is important to first understand how the motivations and constraints at stake at a local context can induce phylogenetic biases before trying to assess the relevance of the allocation of reintroduction efforts at larger scales.}, } @article {pmid29531036, year = {2018}, author = {Parnell, AE and Mordhorst, S and Kemper, F and Giurrandino, M and Prince, JP and Schwarzer, NJ and Hofer, A and Wohlwend, D and Jessen, HJ and Gerhardt, S and Einsle, O and Oyston, PCF and Andexer, JN and Roach, PL}, title = {Substrate recognition and mechanism revealed by ligand-bound polyphosphate kinase 2 structures.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3350-3355}, pmid = {29531036}, issn = {1091-6490}, mesh = {Crystallography, X-Ray ; Deinococcus/*enzymology ; Kinetics ; Ligands ; Phosphorylation ; Phosphotransferases (Phosphate Group Acceptor)/*chemistry/*metabolism ; Polyphosphates/*metabolism ; Protein Conformation ; Substrate Specificity ; }, abstract = {Inorganic polyphosphate is a ubiquitous, linear biopolymer built of up to thousands of phosphate residues that are linked by energy-rich phosphoanhydride bonds. Polyphosphate kinases of the family 2 (PPK2) use polyphosphate to catalyze the reversible phosphorylation of nucleotide phosphates and are highly relevant as targets for new pharmaceutical compounds and as biocatalysts for cofactor regeneration. PPK2s can be classified based on their preference for nucleoside mono- or diphosphates or both. The detailed mechanism of PPK2s and the molecular basis for their substrate preference is unclear, which is mainly due to the lack of high-resolution structures with substrates or substrate analogs. Here, we report the structural analysis and comparison of a class I PPK2 (ADP-phosphorylating) and a class III PPK2 (AMP- and ADP-phosphorylating), both complexed with polyphosphate and/or nucleotide substrates. Together with complementary biochemical analyses, these define the molecular basis of nucleotide specificity and are consistent with a Mg2+ catalyzed in-line phosphoryl transfer mechanism. This mechanistic insight will guide the development of PPK2 inhibitors as potential antibacterials or genetically modified PPK2s that phosphorylate alternative substrates.}, } @article {pmid29531035, year = {2018}, author = {Kraynyukova, N and Tchumatchenko, T}, title = {Stabilized supralinear network can give rise to bistable, oscillatory, and persistent activity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3464-3469}, pmid = {29531035}, issn = {1091-6490}, mesh = {Action Potentials/*physiology ; Cerebral Cortex/*physiology ; Humans ; *Models, Neurological ; Nerve Net/*physiology ; *Neural Networks (Computer) ; }, abstract = {A hallmark of cortical circuits is their versatility. They can perform multiple fundamental computations such as normalization, memory storage, and rhythm generation. Yet it is far from clear how such versatility can be achieved in a single circuit, given that specialized models are often needed to replicate each computation. Here, we show that the stabilized supralinear network (SSN) model, which was originally proposed for sensory integration phenomena such as contrast invariance, normalization, and surround suppression, can give rise to dynamic cortical features of working memory, persistent activity, and rhythm generation. We study the SSN model analytically and uncover regimes where it can provide a substrate for working memory by supporting two stable steady states. Furthermore, we prove that the SSN model can sustain finite firing rates following input withdrawal and present an exact connectivity condition for such persistent activity. In addition, we show that the SSN model can undergo a supercritical Hopf bifurcation and generate global oscillations. Based on the SSN model, we outline the synaptic and neuronal mechanisms underlying computational versatility of cortical circuits. Our work shows that the SSN is an exactly solvable nonlinear recurrent neural network model that could pave the way for a unified theory of cortical function.}, } @article {pmid29531034, year = {2018}, author = {Liang, Z and Bu, W and Schweighofer, KJ and Walwark, DJ and Harvey, JS and Hanlon, GR and Amoanu, D and Erol, C and Benjamin, I and Schlossman, ML}, title = {Nanoscale view of assisted ion transport across the liquid-liquid interface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1701389115}, pmid = {29531034}, issn = {1091-6490}, abstract = {During solvent extraction, amphiphilic extractants assist the transport of metal ions across the liquid-liquid interface between an aqueous ionic solution and an organic solvent. Investigations of the role of the interface in ion transport challenge our ability to probe fast molecular processes at liquid-liquid interfaces on nanometer-length scales. Recent development of a thermal switch for solvent extraction has addressed this challenge, which has led to the characterization by X-ray surface scattering of interfacial intermediate states in the extraction process. Here, we review and extend these earlier results. We find that trivalent rare earth ions, Y(III) and Er(III), combine with bis(hexadecyl) phosphoric acid (DHDP) extractants to form inverted bilayer structures at the interface; these appear to be condensed phases of small ion-extractant complexes. The stability of this unconventional interfacial structure is verified by molecular dynamics simulations. The ion-extractant complexes at the interface are an intermediate state in the extraction process, characterizing the moment at which ions have been transported across the aqueous-organic interface, but have not yet been dispersed in the organic phase. In contrast, divalent Sr(II) forms an ion-extractant complex with DHDP that leaves it exposed to the water phase; this result implies that a second process that transports Sr(II) across the interface has yet to be observed. Calculations demonstrate that the budding of reverse micelles formed from interfacial Sr(II) ion-extractant complexes could transport Sr(II) across the interface. Our results suggest a connection between the observed interfacial structures and the extraction mechanism, which ultimately affects the extraction selectivity and kinetics.}, } @article {pmid29531033, year = {2018}, author = {Allison, DB and Shiffrin, RM and Stodden, V}, title = {Reproducibility of research: Issues and proposed remedies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2561-2562}, pmid = {29531033}, issn = {1091-6490}, } @article {pmid29531032, year = {2018}, author = {Li, G and Bhatt, M and Wang, M and Mbuagbaw, L and Samaan, Z and Thabane, L}, title = {Enhancing primary reports of randomized controlled trials: Three most common challenges and suggested solutions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2595-2599}, pmid = {29531032}, issn = {1091-6490}, mesh = {Humans ; Peer Review/standards ; Publications/*standards ; Quality Control ; Randomized Controlled Trials as Topic/methods/*standards ; Research Design/standards ; }, abstract = {Evidence from a well-designed randomized controlled trial (RCT) is generally considered to be the gold standard that can inform clinical practice and guide decision-making. However, several deficiencies in the reporting of RCTs have frequently been identified, including incomplete, selective, and biased or inconsistent reporting. Such suboptimal reporting may lead to irreproducible results, substantial waste of resources, impaired study validity, erosion of public trust in science, and a high risk of research misconduct. In this article, we present an overview of the reporting of RCTs in the biomedical literature with a focus on the three most common reporting problems: (i) lack of adherence to reporting guidelines, (ii) inconsistencies between trial protocols or registrations and full reports, and (iii) inconsistencies between abstracts and their corresponding full reports. Unsatisfactory levels of adherence to guidelines and frequent inconsistencies between protocols or registrations and full reports, and between abstracts and full reports, were consistently found in various biomedical research fields. A variety of factors were found to be associated with these reporting challenges. Improved reporting can build public trust and credibility of science, save resources, and enhance the ethical integrity of research. Therefore, joint efforts from the various sectors of the biomedical community (researchers, journal editors and reviewers, educators, healthcare providers, and other research consumers) are needed to reduce and reverse the current suboptimal state of RCT reporting in the literature.}, } @article {pmid29531031, year = {2018}, author = {Tomasella, E and Bechelli, L and Ogando, MB and Mininni, C and Di Guilmi, MN and De Fino, F and Zanutto, S and Elgoyhen, AB and Marin-Burgin, A and Gelman, DM}, title = {Deletion of dopamine D2 receptors from parvalbumin interneurons in mouse causes schizophrenia-like phenotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3476-3481}, pmid = {29531031}, issn = {1091-6490}, mesh = {Animals ; Antipsychotic Agents/*pharmacology ; *Drug Resistance ; Interneurons/*metabolism ; Male ; Mice ; Mice, Knockout ; Parvalbumins/genetics/*metabolism ; Phenotype ; Receptors, Dopamine D2/*physiology ; Schizophrenia/drug therapy/*etiology/metabolism ; Synaptic Transmission ; }, abstract = {Excessive dopamine neurotransmission underlies psychotic episodes as observed in patients with some types of bipolar disorder and schizophrenia. The dopaminergic hypothesis was postulated after the finding that antipsychotics were effective to halt increased dopamine tone. However, there is little evidence for dysfunction within the dopaminergic system itself. Alternatively, it has been proposed that excessive afferent activity onto ventral tegmental area dopaminergic neurons, particularly from the ventral hippocampus, increase dopamine neurotransmission, leading to psychosis. Here, we show that selective dopamine D2 receptor deletion from parvalbumin interneurons in mouse causes an impaired inhibitory activity in the ventral hippocampus and a dysregulated dopaminergic system. Conditional mutant animals show adult onset of schizophrenia-like behaviors and molecular, cellular, and physiological endophenotypes as previously described from postmortem brain studies of patients with schizophrenia. Our findings show that dopamine D2 receptor expression on parvalbumin interneurons is required to modulate and limit pyramidal neuron activity, which may prevent the dysregulation of the dopaminergic system.}, } @article {pmid29531030, year = {2018}, author = {Vighi, E and Trifunović, D and Veiga-Crespo, P and Rentsch, A and Hoffmann, D and Sahaboglu, A and Strasser, T and Kulkarni, M and Bertolotti, E and van den Heuvel, A and Peters, T and Reijerkerk, A and Euler, T and Ueffing, M and Schwede, F and Genieser, HG and Gaillard, P and Marigo, V and Ekström, P and Paquet-Durand, F}, title = {Combination of cGMP analogue and drug delivery system provides functional protection in hereditary retinal degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2997-E3006}, pmid = {29531030}, issn = {1091-6490}, mesh = {Animals ; Blood-Retinal Barrier/drug effects/*metabolism ; Cyclic GMP/*administration & dosage/*analogs & derivatives/pharmacology ; Cyclic GMP-Dependent Protein Kinases/metabolism ; *Disease Models, Animal ; *Drug Delivery Systems ; Liposomes ; Mice ; Photoreceptor Cells/metabolism ; Retina/drug effects/metabolism ; Retinal Degeneration/*drug therapy/metabolism ; Signal Transduction/drug effects ; }, abstract = {Inherited retinal degeneration (RD) is a devastating and currently untreatable neurodegenerative condition that leads to loss of photoreceptor cells and blindness. The vast genetic heterogeneity of RD, the lack of "druggable" targets, and the access-limiting blood-retinal barrier (BRB) present major hurdles toward effective therapy development. Here, we address these challenges (i) by targeting cGMP (cyclic guanosine- 3',5'-monophosphate) signaling, a disease driver common to different types of RD, and (ii) by combining inhibitory cGMP analogs with a nanosized liposomal drug delivery system designed to facilitate transport across the BRB. Based on a screen of several cGMP analogs we identified an inhibitory cGMP analog that interferes with activation of photoreceptor cell death pathways. Moreover, we found liposomal encapsulation of the analog to achieve efficient drug targeting to the neuroretina. This pharmacological treatment markedly preserved in vivo retinal function and counteracted photoreceptor degeneration in three different in vivo RD models. Taken together, we show that a defined class of compounds for RD treatment in combination with an innovative drug delivery method may enable a single type of treatment to address genetically divergent RD-type diseases.}, } @article {pmid29531029, year = {2018}, author = {}, title = {Correction for Slik et al., Phylogenetic classification of the world's tropical forests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E3067}, doi = {10.1073/pnas.1803346115}, pmid = {29531029}, issn = {1091-6490}, } @article {pmid29531028, year = {2018}, author = {Koo, DH and Molin, WT and Saski, CA and Jiang, J and Putta, K and Jugulam, M and Friebe, B and Gill, BS}, title = {Extrachromosomal circular DNA-based amplification and transmission of herbicide resistance in crop weed Amaranthus palmeri.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3332-3337}, pmid = {29531028}, issn = {1091-6490}, mesh = {3-Phosphoshikimate 1-Carboxyvinyltransferase/*genetics ; Amaranthus/drug effects/enzymology/*genetics ; Chromosomes, Plant ; *DNA, Circular ; *Gene Amplification ; *Gene Expression Regulation, Plant ; Glycine/analogs & derivatives/pharmacology ; Herbicide Resistance/*genetics ; Herbicides/*pharmacology ; }, abstract = {Gene amplification has been observed in many bacteria and eukaryotes as a response to various selective pressures, such as antibiotics, cytotoxic drugs, pesticides, herbicides, and other stressful environmental conditions. An increase in gene copy number is often found as extrachromosomal elements that usually contain autonomously replicating extrachromosomal circular DNA molecules (eccDNAs). Amaranthus palmeri, a crop weed, can develop herbicide resistance to glyphosate [N-(phosphonomethyl) glycine] by amplification of the 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS) gene, the molecular target of glyphosate. However, biological questions regarding the source of the amplified EPSPS, the nature of the amplified DNA structures, and mechanisms responsible for maintaining this gene amplification in cells and their inheritance remain unknown. Here, we report that amplified EPSPS copies in glyphosate-resistant (GR) A. palmeri are present in the form of eccDNAs with various conformations. The eccDNAs are transmitted during cell division in mitosis and meiosis to the soma and germ cells and the progeny by an as yet unknown mechanism of tethering to mitotic and meiotic chromosomes. We propose that eccDNAs are one of the components of McClintock's postulated innate systems [McClintock B (1978) Stadler Genetics Symposium] that can rapidly produce soma variation, amplify EPSPS genes in the sporophyte that are transmitted to germ cells, and modulate rapid glyphosate resistance through genome plasticity and adaptive evolution.}, } @article {pmid29531027, year = {2018}, author = {van Zonneveld, M and Larranaga, N and Blonder, B and Coradin, L and Hormaza, JI and Hunter, D}, title = {Human diets drive range expansion of megafauna-dispersed fruit species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3326-3331}, pmid = {29531027}, issn = {1091-6490}, mesh = {Animals ; Biodiversity ; *Diet ; *Ecosystem ; *Fossils ; Fruit/*chemistry/classification ; Humans ; *Mammals ; *Plant Dispersal ; }, abstract = {Neotropical fruit species once dispersed by Pleistocene megafauna have regained relevance in diversifying human diets to address malnutrition. Little is known about the historic interactions between humans and these fruit species. We quantified the human role in modifying geographic and environmental ranges of Neotropical fruit species by comparing the distribution of megafauna-dispersed fruit species that have been part of both human and megafauna diets with fruit species that were exclusively part of megafauna diets. Three quarters of the fruit species that were once dispersed by megafauna later became part of human diets. Our results suggest that, because of extensive dispersal and management, humans have expanded the geographic and environmental ranges of species that would otherwise have suffered range contraction after extinction of megafauna. Our results suggest that humans have been the principal dispersal agent for a large proportion of Neotropical fruit species between Central and South America. Our analyses help to identify range segments that may hold key genetic diversity resulting from historic interactions between humans and these fruit species. These genetic resources are a fundamental source to improve and diversify contemporary food systems and to maintain critical ecosystem functions. Public, private, and societal initiatives that stimulate dietary diversity could expand the food usage of these megafauna-dispersed fruit species to enhance human nutrition in combination with biodiversity conservation.}, } @article {pmid29531026, year = {2018}, author = {Hohmann, U and Santiago, J and Nicolet, J and Olsson, V and Spiga, FM and Hothorn, LA and Butenko, MA and Hothorn, M}, title = {Mechanistic basis for the activation of plant membrane receptor kinases by SERK-family coreceptors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3488-3493}, pmid = {29531026}, issn = {1091-6490}, mesh = {Arabidopsis/growth & development/*metabolism ; Arabidopsis Proteins/chemistry/*metabolism ; Kinetics ; Ligands ; Plant Development ; Protein Binding ; Protein Conformation ; Protein Kinases/chemistry/*metabolism ; Protein-Serine-Threonine Kinases/chemistry/*metabolism ; Proteins/chemistry/*metabolism ; Receptors, Cell Surface/chemistry/*metabolism ; Signal Transduction ; }, abstract = {Plant-unique membrane receptor kinases with leucine-rich repeat ectodomains (LRR-RKs) can sense small molecule, peptide, and protein ligands. Many LRR-RKs require SERK-family coreceptor kinases for high-affinity ligand binding and receptor activation. How one coreceptor can contribute to the specific binding of distinct ligands and activation of different LRR-RKs is poorly understood. Here we quantitatively analyze the contribution of SERK3 to ligand binding and activation of the brassinosteroid receptor BRI1 and the peptide hormone receptor HAESA. We show that while the isolated receptors sense their respective ligands with drastically different binding affinities, the SERK3 ectodomain binds the ligand-associated receptors with very similar binding kinetics. We identify residues in the SERK3 N-terminal capping domain, which allow for selective steroid and peptide hormone recognition. In contrast, residues in the SERK3 LRR core form a second, constitutive receptor-coreceptor interface. Genetic analyses of protein chimera between BRI1 and SERK3 define that signaling-competent complexes are formed by receptor-coreceptor heteromerization in planta. A functional BRI1-HAESA chimera suggests that the receptor activation mechanism is conserved among different LRR-RKs, and that their signaling specificity is encoded in the kinase domain of the receptor. Our work pinpoints the relative contributions of receptor, ligand, and coreceptor to the formation and activation of SERK-dependent LRR-RK signaling complexes regulating plant growth and development.}, } @article {pmid29531025, year = {2018}, author = {Boutron, I and Ravaud, P}, title = {Misrepresentation and distortion of research in biomedical literature.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2613-2619}, pmid = {29531025}, issn = {1091-6490}, mesh = {Biomedical Research/*standards ; Humans ; Literature ; Peer Review, Research/standards ; Publications/*standards ; }, abstract = {Publication in peer-reviewed journals is an essential step in the scientific process. However, publication is not simply the reporting of facts arising from a straightforward analysis thereof. Authors have broad latitude when writing their reports and may be tempted to consciously or unconsciously "spin" their study findings. Spin has been defined as a specific intentional or unintentional reporting that fails to faithfully reflect the nature and range of findings and that could affect the impression the results produce in readers. This article, based on a literature review, reports the various practices of spin from misreporting by "beautification" of methods to misreporting by misinterpreting the results. It provides data on the prevalence of some forms of spin in specific fields and the possible effects of some types of spin on readers' interpretation and research dissemination. We also discuss why researchers would spin their reports and possible ways to avoid it.}, } @article {pmid29531024, year = {2018}, author = {Ohmura, T and Nishigami, Y and Taniguchi, A and Nonaka, S and Manabe, J and Ishikawa, T and Ichikawa, M}, title = {Simple mechanosense and response of cilia motion reveal the intrinsic habits of ciliates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3231-3236}, pmid = {29531024}, issn = {1091-6490}, mesh = {Cilia/physiology ; Ciliophora/cytology/*physiology ; Fluorescence ; Locomotion ; *Models, Biological ; Tetrahymena pyriformis/*cytology/physiology ; Water ; }, abstract = {An important habit of ciliates, namely, their behavioral preference for walls, is revealed through experiments and hydrodynamic simulations. A simple mechanical response of individual ciliary beating (i.e., the beating is stalled by the cilium contacting a wall) can solely determine the sliding motion of the ciliate along the wall and result in a wall-preferring behavior. Considering ciliate ethology, this mechanosensing system is likely an advantage in the single cell's ability to locate nutrition. In other words, ciliates can skillfully use both the sliding motion to feed on a surface and the traveling motion in bulk water to locate new surfaces according to the single "swimming" mission.}, } @article {pmid29531023, year = {2018}, author = {Schuemie, MJ and Hripcsak, G and Ryan, PB and Madigan, D and Suchard, MA}, title = {Empirical confidence interval calibration for population-level effect estimation studies in observational healthcare data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2571-2577}, pmid = {29531023}, issn = {1091-6490}, support = {R01 LM006910/LM/NLM NIH HHS/United States ; }, mesh = {*Bias ; Calibration/*standards ; Confidence Intervals ; Health Services Research/*standards/*statistics & numerical data ; Humans ; *Observational Studies as Topic ; Research Design/standards/statistics & numerical data ; }, abstract = {Observational healthcare data, such as electronic health records and administrative claims, offer potential to estimate effects of medical products at scale. Observational studies have often been found to be nonreproducible, however, generating conflicting results even when using the same database to answer the same question. One source of discrepancies is error, both random caused by sampling variability and systematic (for example, because of confounding, selection bias, and measurement error). Only random error is typically quantified but converges to zero as databases become larger, whereas systematic error persists independent from sample size and therefore, increases in relative importance. Negative controls are exposure-outcome pairs, where one believes no causal effect exists; they can be used to detect multiple sources of systematic error, but interpreting their results is not always straightforward. Previously, we have shown that an empirical null distribution can be derived from a sample of negative controls and used to calibrate P values, accounting for both random and systematic error. Here, we extend this work to calibration of confidence intervals (CIs). CIs require positive controls, which we synthesize by modifying negative controls. We show that our CI calibration restores nominal characteristics, such as 95% coverage of the true effect size by the 95% CI. We furthermore show that CI calibration reduces disagreement in replications of two pairs of conflicting observational studies: one related to dabigatran, warfarin, and gastrointestinal bleeding and one related to selective serotonin reuptake inhibitors and upper gastrointestinal bleeding. We recommend CI calibration to improve reproducibility of observational studies.}, } @article {pmid29530606, year = {2018}, author = {Mack, SG and Turner, RL and Dwyer, DJ}, title = {Achieving a Predictive Understanding of Antimicrobial Stress Physiology through Systems Biology.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {296-312}, doi = {10.1016/j.tim.2018.02.004}, pmid = {29530606}, issn = {1878-4380}, abstract = {The dramatic spread and diversity of antibiotic-resistant pathogens has significantly reduced the efficacy of essentially all antibiotic classes, bringing us ever closer to a postantibiotic era. Exacerbating this issue, our understanding of the multiscale physiological impact of antimicrobial challenge on bacterial pathogens remains incomplete. Concerns over resistance and the need for new antibiotics have motivated the collection of omics measurements to provide systems-level insights into antimicrobial stress responses for nearly 20 years. Although technological advances have markedly improved the types and resolution of such measurements, continued development of mathematical frameworks aimed at providing a predictive understanding of complex antimicrobial-associated phenotypes is critical to maximize the utility of multiscale data. Here we highlight recent efforts utilizing systems biology to enhance our knowledge of antimicrobial stress physiology. We provide a brief historical perspective of antibiotic-focused omics measurements, highlight new measurement discoveries and trends, discuss examples and opportunities for integrating measurements with mathematical models, and describe future challenges for the field.}, } @article {pmid29530499, year = {2018}, author = {Chen, JM and Poyarkov, NA and Suwannapoom, C and Lathrop, A and Wu, YH and Zhou, WW and Yuan, ZY and Jin, JQ and Chen, HM and Liu, HQ and Nguyen, TQ and Nguyen, SN and Duong, TV and Eto, K and Nishikawa, K and Matsui, M and Orlov, NL and Stuart, BL and Brown, RM and Rowley, JJL and Murphy, RW and Wang, YY and Che, J}, title = {Large-scale phylogenetic analyses provide insights into unrecognized diversity and historical biogeography of Asian leaf-litter frogs, genus Leptolalax (Anura: Megophryidae).}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {162-171}, doi = {10.1016/j.ympev.2018.02.020}, pmid = {29530499}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification ; Asia ; Base Sequence ; Bayes Theorem ; *Biodiversity ; *Phylogeny ; Phylogeography ; Species Specificity ; Time Factors ; }, abstract = {Southeast Asia and southern China (SEA-SC) harbor a highly diverse and endemic flora and fauna that is under increasing threat. An understanding of the biogeographical history and drivers of this diversity is lacking, especially in some of the most diverse and threatened groups. The Asian leaf-litter frog genus Leptolalax Dubois 1980 is a forest-dependent genus distributed throughout SEA-SC, making it an ideal study group to examine specific biogeographic hypotheses. In addition, the diversity of this genus remains poorly understood, and the phylogenetic relationships among species of Leptolalax and closely related Leptobrachella Smith 1928 remain unclear. Herein, we evaluate species-level diversity based on 48 of the 53 described species from throughout the distribution of Leptolalax. Molecular analyses reveal many undescribed species, mostly in southern China and Indochina. Our well-resolved phylogeny based on multiple nuclear DNA markers shows that Leptolalax is not monophyletic with respect to Leptobrachella and, thus, we assign the former to being a junior synonym of the latter. Similarly, analyses reject monophyly of the two subgenera of Leptolalax. The diversification pattern of the group is complex, involving a high degree of sympatry and prevalence of microendemic species. Northern Sundaland (Borneo) and eastern Indochina (Vietnam) appear to have played pivotal roles as geographical centers of diversification, and paleoclimatic changes and tectonic movements seem to have driven the major divergence of clades. Analyses fail to reject an "upstream" colonization hypothesis, and, thus, the genus appears to have originated in Sundaland and then colonized mainland Asia. Our results reveal that both vicariance and dispersal are responsible for current distribution patterns in the genus.}, } @article {pmid29530498, year = {2018}, author = {Vachaspati, P and Warnow, T}, title = {SVDquest: Improving SVDquartets species tree estimation using exact optimization within a constrained search space.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {122-136}, doi = {10.1016/j.ympev.2018.03.006}, pmid = {29530498}, issn = {1095-9513}, mesh = {Computer Simulation ; Databases, Genetic ; Genetic Speciation ; Genomics/*methods ; Models, Genetic ; *Phylogeny ; Species Specificity ; }, abstract = {Species tree estimation from multi-locus datasets is complicated by processes such as incomplete lineage sorting (ILS) that result in different loci having different trees. Summary methods, which estimate species trees by combining gene trees, are popular but their accuracy is impaired by gene tree estimation error. Other approaches have been developed that only use the site patterns to estimate the species tree, and so are not impacted by gene tree estimation issues. In particular, PAUP∗ provides a method in which SVDquartets is used to compute a set Q of quartet trees (i.e., trees on four leaves), and then a heuristic search is used to combine the quartet trees into a species tree T, seeking to maximize the number of quartet trees in Q that agree with T. The PAUP∗ method based on SVDquartets (henceforth referred to as SVDquartets + PAUP∗) is increasingly used in phylogenomic studies due to its ability to reconstruct species trees without needing to estimate accurate gene trees. We present SVDquest∗, a new method for constructing species trees using site patterns that is guaranteed to produce species trees that satisfy at least as many quartet trees as SVDquartets + PAUP∗. We show that SVDquest∗ is competitive with ASTRAL and ASTRID (two leading summary methods) in terms of topological accuracy, and tends to be more accurate than ASTRAL and ASTRID under conditions with relatively high gene tree estimation error. SVDquest∗ is available in open source form at https://github.com/pranjalv123/SVDquest.}, } @article {pmid29530451, year = {2018}, author = {Jin, Y and Weinstein, DC}, title = {Pitx1 regulates cement gland development in Xenopus laevis through activation of transcriptional targets and inhibition of BMP signaling.}, journal = {Developmental biology}, volume = {437}, number = {1}, pages = {41-49}, pmid = {29530451}, issn = {1095-564X}, support = {R03 HD077015/HD/NICHD NIH HHS/United States ; R15 GM124577/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Bone Morphogenetic Proteins/*metabolism ; Cell Differentiation/genetics ; Ectoderm/*embryology/metabolism ; Embryo, Nonmammalian ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/metabolism ; Immunoprecipitation ; In Situ Hybridization ; Organogenesis/genetics ; Paired Box Transcription Factors/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, RNA ; Signal Transduction ; Xenopus Proteins/*genetics/metabolism ; Xenopus laevis ; }, abstract = {The cement gland in Xenopus laevis has long been used as a model to study the interplay of cell signaling and transcription factors during embryogenesis. It has been shown that an intermediate level of Bone Morphogenetic Protein (BMP) signaling is essential for cement gland formation. In addition, several transcription factors have been linked to cement gland development. One of these, the homeodomain-containing protein Pitx1, can generate ectopic cement gland formation; however, the mechanisms underlying this process remain obscure. We report here, for the first time, a requirement for Pitx proteins in cement gland formation, in vivo: knockdown of both pitx1 and the closely related pitx2c inhibit endogenous cement gland formation. Pitx1 transcriptionally activates cement gland differentiation genes through both direct and indirect mechanisms, and functions as a transcriptional activator to inhibit BMP signaling. This inhibition, required for the expression of pitx genes, is partially mediated by Pitx1-dependent follistatin expression. Complete suppression of BMP signaling inhibits induction of cement gland markers by Pitx1; furthermore, we find that Pitx1 physically interacts with Smad1, an intracellular transducer of BMP signaling. We propose a model of cement gland formation in which Pitx1 limits local BMP signaling within the cement gland primordium, and recruits Smad1 to activate direct downstream targets.}, } @article {pmid29530446, year = {2018}, author = {Gunalan, K and Niangaly, A and Thera, MA and Doumbo, OK and Miller, LH}, title = {Plasmodium vivax Infections of Duffy-Negative Erythrocytes: Historically Undetected or a Recent Adaptation?.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {420-429}, doi = {10.1016/j.pt.2018.02.006}, pmid = {29530446}, issn = {1471-5007}, support = {R01 AI099628/AI/NIAID NIH HHS/United States ; Z01 AI000241-27/NULL/Intramural NIH HHS/United States ; }, mesh = {*Adaptation, Physiological ; Africa ; Duffy Blood-Group System ; Erythrocytes/*parasitology ; Humans ; Ligands ; Malaria, Vivax/*parasitology ; Plasmodium vivax/*physiology ; }, abstract = {Plasmodium vivax is the main cause of malarial disease in Asia and South America. Plasmodium vivax infection was thought to be absent in African populations who are Duffy blood group antigen negative (Duffy-negative). However, many cases of P. vivax infection have recently been observed in Duffy-negative Africans. This raises the question: were P. vivax infections in Duffy-negative populations previously missed or has P. vivax adapted to infect Duffy-negative populations? This review focuses on recent P. vivax findings in Africa and reports views on the parasite ligands that may play a role in Duffy-negative P. vivax infections. In addition, clues gained from studying P. vivax infection of reticulocytes are presented, which may provide possible avenues for establishing P. vivax culture in vitro.}, } @article {pmid29530086, year = {2018}, author = {Onyango, CG and Ogonda, L and Guyah, B and Okoth, P and Shiluli, C and Humwa, F and Opollo, V}, title = {Seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors in Homabay, Kisumu and Siaya counties in western Kenya.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {171}, pmid = {29530086}, issn = {1756-0500}, support = {HELB/45/003/VL///HIGHER EDUCATION LOAN BOARD (HELB)/ ; }, mesh = {Adolescent ; Adult ; Aged ; Blood Donors/*statistics & numerical data ; Cross-Sectional Studies ; Female ; HIV Infections/*blood/epidemiology ; Hepatitis B/*blood/epidemiology ; Hepatitis C/*blood/epidemiology ; Humans ; Kenya/epidemiology ; Male ; Middle Aged ; Seroepidemiologic Studies ; Syphilis/*blood/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Since the implementation of a series of blood donation safety improvements in Kenya, information about seroprevalence and determinants of transfusion transmissible infections among voluntary blood donors especially in high HIV burden regions of Homabay, Kisumu and Siaya counties remain scanty. A cross-sectional study examining HIV, syphilis, hepatitis B and C virus sero-markers and associated determinants was conducted among voluntary blood donors. Their demographic characteristics and previous risk exposure were recorded in a pre-donation questionnaire, while blood samples collected were screened for hepatitis B, hepatitis C, human immunodeficiency viruses by ELISA and RPR (syphilis), then confirmed using CMIA.

RESULTS: Overall TTIs seroprevalence was 114 (9.4%), distributed among HIV, HBV, HCV and syphilis at 14 (1.15%), 42 (3.46%), 39 (3.21%) and 19 (1.56%), respectively, with co-infections of 3 (0.25%). There were no significant differences in proportions distributions among demographic variables. However, high risk sex was significantly associated with higher odds of HBV infections [> 1 partner vs. 0-1 partner; odd ratio (OR) 2.60; 95% confidence interval (CI) 1.098-6.86; p = 0.046]. In conclusion, a substantial percentage of blood donors still harbor transfusion transmissible infections despite recent safety improvements with greater majority cases caused by HBV infections arising from previous exposure to high risk sex.}, } @article {pmid29530079, year = {2018}, author = {Majowicz, SE and Parmley, EJ and Carson, C and Pintar, K}, title = {Identifying non-traditional stakeholders with whom to engage, when mitigating antimicrobial resistance in foodborne pathogens (Canada).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {170}, pmid = {29530079}, issn = {1756-0500}, mesh = {Canada ; *Community-Based Participatory Research ; *Drug Resistance, Microbial ; *Food Microbiology ; *Food Safety ; *Health Policy ; *Public Health ; }, abstract = {OBJECTIVE: Antimicrobial resistance (AMR) is a critical public health issue that involves interrelationships between people, animals, and the environment. Traditionally, interdisciplinary efforts to mitigate AMR in the food chain have involved public health, human and veterinary medicine, and agriculture stakeholders. Our objective was to identify a more diverse range of stakeholders, beyond those traditionally engaged in AMR mitigation efforts, via diagramming both proximal and distal factors impacting, or impacted by, use and resistance along the Canadian food chain.

RESULTS: We identified multiple stakeholders that are not traditionally engaged by public health when working to mitigate AMR in the food chain, including those working broadly in the area of food (e.g., nutrition, food security, international market economists) and health (e.g., health communication, program evaluation), as well as in domains as diverse as law, politics, demography, education, and social innovation. These findings can help researchers and policymakers who work on issues related to AMR in the food chain to move beyond engaging the 'traditional' agri-food stakeholders (e.g., veterinarians, farmers), to also engage those from the wider domains identified here, as potential stakeholders in their AMR mitigation efforts.}, } @article {pmid29530078, year = {2018}, author = {Chia, D and Powell, L and Lee, V and Haghighi, MM and Podberscek, A and Ding, D and Sherrington, C and Stamatakis, E}, title = {Sociodemographic correlates of prospective dog owners' intentions to participate in controlled trials of dog ownership and human health.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {169}, pmid = {29530078}, issn = {1756-0500}, mesh = {Adult ; Aged ; Animals ; *Clinical Trials as Topic ; Dogs ; Female ; Humans ; Intention ; Male ; Middle Aged ; Ownership ; *Patient Selection ; *Pets ; *Public Health ; Young Adult ; }, abstract = {OBJECTIVE: Dog ownership is popular, with research suggesting improvements in physical and psychological health of dog owners. However, majority of these studies were not investigator-controlled. Ethical and practical implications arising from the intervention exposure (dog ownership) result in recruitment difficulties. A fit-for-purpose design, such as delaying dog adoption until after data collection, could alleviate such issues. The purpose of this study was to explore intentions and possible incentives for participation in investigator-controlled trials examining the effects of dog ownership on human physical and psychological health.

RESULTS: Female (OR 1.64, 95% CI 1.31-2.04) and older (OR 65+ years 1.49, 95% CI 1.06-2.10) participants were more likely to be interested in taking part in a study investigating the health benefits of dog ownership. Majority reported no incentive was necessary for participation (57%), while others preferred pet food supplies (37%), or vouchers for veterinary care (32%). Over half of participants (53%) were willing postpone adoption for up to 3 months to participate in an investigator-controlled trial. The results of the study, showing majority of participants interested in participating in future studies examining the health benefits of dog ownership and without incentives, provides insight to methodical directions for future studies.}, } @article {pmid29530013, year = {2018}, author = {Niepoth, N and Ellers, J and Henry, LM}, title = {Symbiont interactions with non-native hosts limit the formation of new symbioses.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {27}, pmid = {29530013}, issn = {1471-2148}, support = {626616//H2020 Marie Skłodowska-Curie Actions/International ; NE/M018016/1//Natural Environment Research Council/International ; 865.12.003//Nederlandse Organisatie voor Wetenschappelijk Onderzoek (NL)/International ; }, mesh = {Adaptation, Physiological ; Animals ; Aphids/genetics/*microbiology ; Enterobacteriaceae/*physiology ; Feeding Behavior ; Fertility ; Genotype ; Phenotype ; Plants/parasitology ; *Symbiosis ; }, abstract = {BACKGROUND: Facultative symbionts are common in eukaryotes and can provide their hosts with significant fitness benefits. Despite the advantage of carrying these microbes, they are typically only found in a fraction of the individuals within a population and are often non-randomly distributed among host populations. It is currently unclear why facultative symbionts are only found in certain host individuals and populations. Here we provide evidence for a mechanism to help explain this phenomenon: that when symbionts interact with non-native host genotypes it can limit the horizontal transfer of symbionts to particular host lineages and populations of related hosts.

RESULTS: Using reciprocal transfections of the facultative symbiont Hamiltonella defensa into different pea aphid clones, we demonstrate that particular symbiont strains can cause high host mortality and inhibit offspring production when injected into aphid clones other than their native host lineage. However, once established, the symbiont's ability to protect against parasitoids was not influenced by its origin. We then demonstrate that H. defensa is also more likely to establish a symbiotic relationship with aphid clones from a plant-adapted population (biotype) that typically carry H. defensa in nature, compared to clones from a biotype that does not normally carry this symbiont.

CONCLUSIONS: These results provide evidence that certain aphid lineages and populations of related hosts are predisposed to establishing a symbiotic relationship with H. defensa. Our results demonstrate that host-symbiont genotype interactions represent a potential barrier to horizontal transmission that can limit the spread of symbionts, and adaptive traits they carry, to certain host lineages.}, } @article {pmid29529991, year = {2018}, author = {Yang, S and Wang, J and Ng, RT}, title = {Inferring RNA sequence preferences for poorly studied RNA-binding proteins based on co-evolution.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {96}, pmid = {29529991}, issn = {1471-2105}, support = {lsarp//Genome Canada/International ; cnfn//Natural Sciences and Engineering Research Council of Canada/International ; }, mesh = {*Algorithms ; Binding Sites ; *Evolution, Molecular ; RNA/*chemistry/*metabolism ; RNA-Binding Proteins/*chemistry/*metabolism ; }, abstract = {BACKGROUND: Characterizing the binding preference of RNA-binding proteins (RBP) is essential for us to understand the interaction between an RBP and its RNA targets, and to decipher the mechanism of post-transcriptional regulation. Experimental methods have been used to generate protein-RNA binding data for a number of RBPs in vivo and in vitro. Utilizing the binding data, a couple of computational methods have been developed to detect the RNA sequence or structure preferences of the RBPs. However, the majority of RBPs have not yet been experimentally characterized and lack RNA binding data. For these poorly studied RBPs, the identification of their binding preferences cannot be performed by most existing computational methods because the experimental binding data are prerequisite to these methods.

RESULTS: Here we propose a new method based on co-evolution to predict the sequence preferences for the poorly studied RBPs, waiving the requirement of their binding data. First, we demonstrate the co-evolutionary relationship between RBPs and their RNA partners. We then present a K-nearest neighbors (KNN) based algorithm to infer the sequence preference of an RBP using only the preference information from its homologous RBPs. By benchmarking against several in vitro and in vivo datasets, our proposed method outperforms the existing alternative which uses the closest neighbor's preference on all the datasets. Moreover, it shows comparable performance with two state-of-the-art methods that require the presence of the experimental binding data. Finally, we demonstrate the usage of this method to infer sequence preferences for novel proteins which have no binding preference information available.

CONCLUSION: For a poorly studied RBP, the current methods used to determine its binding preference need experimental data, which is expensive and time consuming. Therefore, determining RBP's preference is not practical in many situations. This study provides an economic solution to infer the sequence preference of such protein based on the co-evolution. The source codes and related datasets are available at https://github.com/syang11/KNN .}, } @article {pmid29529867, year = {2018}, author = {Küster, D}, title = {Social Effects of Tears and Small Pupils Are Mediated by Felt Sadness: An Evolutionary View.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704918761104}, doi = {10.1177/1474704918761104}, pmid = {29529867}, issn = {1474-7049}, mesh = {Adolescent ; Crying/*psychology ; Emotions/*physiology ; Empathy/*physiology ; *Facial Expression ; Female ; Humans ; Male ; Miosis/*psychology ; Photic Stimulation ; *Tears ; Young Adult ; }, abstract = {Small pupils elicit empathic socioemotional responses comparable to those found for emotional tears. This might be understood in an evolutionary context. Intense emotional tearing increases tear film volume and disturbs tear layer uniformity, resulting in blurry vision. A constriction of the pupils may help to mitigate this handicap, which in turn may have resulted in a perceptual association of both signals. However, direct empirical evidence for a role of pupil size in tearful emotional crying is still lacking. The present study examined socioemotional responses to different pupil sizes, combined with the presence (absence) of digitally added tears superimposed upon expressively neutral faces. Data from 50 subjects showed significant effects of observing digitally added tears in avatars, replicating previous findings for increased perceived sadness elicited by tearful photographs. No significant interactions were found between tears and pupil size. However, small pupils likewise elicited a significantly greater wish to help in observers. Further analysis showed a significant serial mediation of the effects of tears on perceived wish to help via perceived and then felt sadness. For pupil size, only felt sadness emerged as a significant mediator of the wish to help. These findings support the notion that pupil constriction in the context of intense sadness may function to counteract blurry vision. Pupil size, like emotional tears, appears to have acquired value as a social signal in this context.}, } @article {pmid29529322, year = {2018}, author = {Melnikov, S and Manakongtreecheep, K and Söll, D}, title = {Revising the Structural Diversity of Ribosomal Proteins Across the Three Domains of Life.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1588-1598}, pmid = {29529322}, issn = {1537-1719}, abstract = {Ribosomal proteins are indispensable components of a living cell, and yet their structures are remarkably diverse in different species. Here we use manually curated structural alignments to provide a comprehensive catalog of structural variations in homologous ribosomal proteins from bacteria, archaea, eukaryotes, and eukaryotic organelles. By resolving numerous ambiguities and errors of automated structural and sequence alignments, we uncover a whole new class of structural variations that reside within seemingly conserved segments of ribosomal proteins. We then illustrate that these variations reflect an apparent adaptation of ribosomal proteins to the specific environments and lifestyles of living species. Finally, we show that most of these structural variations reside within nonglobular extensions of ribosomal proteins-protein segments that are thought to promote ribosome biogenesis by stabilizing the proper folding of ribosomal RNA. We show that although the extensions are thought to be the most ancient peptides on our planet, they are in fact the most rapidly evolving and most structurally and functionally diverse segments of ribosomal proteins. Overall, our work illustrates that, despite being long considered as slowly evolving and highly conserved, ribosomal proteins are more complex and more specialized than is generally recognized.}, } @article {pmid29529207, year = {2018}, author = {Agop-Nersesian, C and Niklaus, L and Wacker, R and Theo Heussler, V}, title = {Host cell cytosolic immune response during Plasmodium liver stage development.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {324-334}, pmid = {29529207}, issn = {1574-6976}, mesh = {Animals ; Cytosol/*immunology/*parasitology ; Hepatocytes/immunology/parasitology ; Host-Parasite Interactions/*immunology ; Humans ; Life Cycle Stages ; Liver/*immunology/*parasitology ; Plasmodium/*growth & development/*immunology ; }, abstract = {Recent years have witnessed a great gain in knowledge regarding parasite-host cell interactions during Plasmodium liver stage development. It is now an accepted fact that a large percentage of sporozoites invading hepatocytes fail to form infectious merozoites. There appears to be a delicate balance between parasite survival and elimination and we now start to understand why this is so. Plasmodium liver stage parasites replicate within the parasitophorous vacuole (PV), formed during invasion by invagination of the host cell plasma membrane. The main interface between the parasite and hepatocyte is the parasitophorous vacuole membrane (PVM) that surrounds the PV. Recently, it was shown that autophagy marker proteins decorate the PVM of Plasmodium liver stage parasites and eliminate a proportion of them by an autophagy-like mechanism. Successfully developing Plasmodium berghei parasites are initially also labeled but in the course of development, they are able to control this host defense mechanism by shedding PVM material into the tubovesicular network (TVN), an extension of the PVM that releases vesicles into the host cell cytoplasm. Better understanding of the molecular events at the PVM/TVN during parasite elimination could be the basis of new antimalarial measures.}, } @article {pmid29529204, year = {2018}, author = {Gunde-Cimerman, N and Plemenitaš, A and Oren, A}, title = {Strategies of adaptation of microorganisms of the three domains of life to high salt concentrations.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {353-375}, doi = {10.1093/femsre/fuy009}, pmid = {29529204}, issn = {1574-6976}, mesh = {*Adaptation, Physiological ; Archaea/*physiology ; *Bacterial Physiological Phenomena ; Chlorophyta/*physiology ; Fungi/*physiology ; Models, Biological ; *Salinity ; }, abstract = {Hypersaline environments with salt concentrations up to NaCl saturation are inhabited by a great diversity of microorganisms belonging to the three domains of life. They all must cope with the low water activity of their environment, but different strategies exist to provide osmotic balance of the cells' cytoplasm with the salinity of the medium. One option used by many halophilic Archaea and a few representatives of the Bacteria is to accumulate salts, mainly KCl and to adapt the entire intracellular machinery to function in the presence of molar concentrations of salts. A more widespread option is the synthesis or accumulation of organic osmotic, so-called compatible solutes. Here, we review the mechanisms of osmotic adaptation in a number of model organisms, including the KCl accumulating Halobacterium salinarum (Archaea) and Salinibacter ruber (Bacteria), Halomonas elongata as a representative of the Bacteria that synthesize organic osmotic solutes, eukaryotic microorganisms including the unicellular green alga Dunaliella salina and the black yeasts Hortaea werneckii and the basidiomycetous Wallemia ichthyophaga, which use glycerol and other compatible solutes. The strategies used by these model organisms and by additional halophilic microorganisms presented are then compared to obtain an integrative picture of the adaptations to life at high salt concentrations in the microbial world.}, } @article {pmid29528562, year = {2018}, author = {Frey, J and Schneider, F and Huhn, T and Spiteller, D and Schink, B and Schleheck, D}, title = {Two enzymes of the acetone degradation pathway of Desulfococcus biacutus: coenzyme B12 -dependent 2-hydroxyisobutyryl-CoA mutase and 3-hydroxybutyryl-CoA dehydrogenase.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {283-292}, doi = {10.1111/1758-2229.12637}, pmid = {29528562}, issn = {1758-2229}, abstract = {Degradation of acetone by the sulfate-reducing bacterium Desulfococcus biacutus involves an acetone-activation reaction different from that used by aerobic or nitrate-reducing bacteria, because the small energy budget of sulfate-reducing bacteria does not allow for major expenditures into ATP-consuming carboxylation reactions. In the present study, an inducible coenzyme B12 -dependent conversion of 2-hydroxyisobutyryl-CoA to 3-hydroxybutyryl-CoA was demonstrated in cell-free extracts of acetone-grown D. biacutus cells, together with a NAD+ -dependent oxidation of 3-hydroxybutyryl-CoA to acetoacetyl-CoA. Genes encoding two mutase subunits and a dehydrogenase, which were found previously to be strongly induced during growth with acetone, were heterologously expressed in E. coli. The activities of the purified recombinant proteins matched with the inducible activities observed in cell-free extracts of acetone-grown D. biacutus: proteins (IMG locus tags) DebiaDRAFT_04573 and 04574 constituted a B12 -dependent 2-hydroxyisobutyryl-CoA/3-hydroxybutyryl-CoA mutase, and DebiaDRAFT_04571 was a 3-hydroxybutyryl-CoA dehydrogenase. Hence, these enzymes play key roles in the degradation of acetone and define an involvement of CoA esters in the pathway. Further, the involvement of 2-hydroxyisobutyryl-CoA strongly indicates that the carbonyl-C2 of acetone is added, most likely, to formyl-CoA through a TDP-dependent enzyme that is co-induced in acetone-grown cells and is encoded in the same gene cluster as the identified mutase and dehydrogenase.}, } @article {pmid29528550, year = {2018}, author = {Robinson, SL and Badalamenti, JP and Dodge, AG and Tassoulas, LJ and Wackett, LP}, title = {Microbial biodegradation of biuret: defining biuret hydrolases within the isochorismatase superfamily.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14094}, pmid = {29528550}, issn = {1462-2920}, abstract = {Biuret is a minor component of urea fertilizer and an intermediate in s-triazine herbicide biodegradation. The microbial metabolism of biuret has never been comprehensively studied. Here, we enriched and isolated bacteria from a potato field that grew on biuret as a sole nitrogen source. We sequenced the genome of the fastest-growing isolate, Herbaspirillum sp. BH-1 and identified genes encoding putative biuret hydrolases (BHs). We purified and characterized a functional BH enzyme from Herbaspirillum sp. BH-1 and two other bacteria from divergent phyla. The BH enzymes reacted exclusively with biuret in the range of 2-11 µmol min-1 mg-1 protein. We then constructed a global protein superfamily network to map structure-function relationships in the BH subfamily and used this to mine > 7000 genomes. High-confidence BH sequences were detected in Actinobacteria, Alpha- and Beta-proteobacteria, and some fungi, archaea and green algae, but not animals or land plants. Unexpectedly, no cyanuric acid hydrolase homologs were detected in > 90% of genomes with BH homologs, suggesting BHs may have arisen independently of s-triazine ring metabolism. This work links genotype to phenotype by enabling accurate genome-mining to predict microbial utilization of biuret. Importantly, it advances understanding of the microbial capacity for biuret biodegradation in agricultural systems.}, } @article {pmid29528548, year = {2018}, author = {Zhu, L and Wu, Q and Deng, C and Zhang, M and Zhang, C and Chen, H and Lu, G and Wei, F}, title = {Adaptive evolution to a high purine and fat diet of carnivorans revealed by gut microbiomes and host genomes.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1711-1722}, doi = {10.1111/1462-2920.14096}, pmid = {29528548}, issn = {1462-2920}, abstract = {Carnivorous members of the Carnivora reside at the apex of food chains and consume meat-only diets, rich in purine, fats and protein. Here, we aimed to identify potential adaptive evolutionary signatures compatible with high purine and fat metabolism based on analysis of host genomes and symbiotic gut microbial metagenomes. We found that the gut microbiomes of carnivorous Carnivora (e.g., Felidae, Canidae) clustered in the same clade, and other clades comprised omnivorous and herbivorous Carnivora (e.g., badgers, bears and pandas). The relative proportions of genes encoding enzymes involved in uric acid degradation were higher in the gut microbiomes of meat-eating carnivorans than plant-eating species. Adaptive amino acid substitutions in two enzymes, carnitine O-palmitoyltransferase 1 (CPT1A) and lipase F (LIPF), which play a role in fat digestion, were identified in Felidae-Candidae species. Carnivorous carnivorans appear to endure diets high in purines and fats via gut microbiomic and genomic adaptations.}, } @article {pmid29528547, year = {2018}, author = {Zhu, G and Wang, S and Li, Y and Zhuang, L and Zhao, S and Wang, C and Kuypers, MMM and Jetten, MSM and Zhu, Y}, title = {Microbial pathways for nitrogen loss in an upland soil.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1723-1738}, doi = {10.1111/1462-2920.14098}, pmid = {29528547}, issn = {1462-2920}, abstract = {The distribution and importance of anaerobic ammonium oxidation (anammox) and nitrite-dependent anaerobic methane oxidation (n-damo) have been identified in aquatic ecosystems; their role in agricultural upland soils however has not yet been well investigated. In this study, we examined spatio-temporal distributions of anammox and n-damo bacteria in soil profiles (300 cm depth) from an agricultural upland. Monitoring nitrogen (N) conversion activity using isotope-tracing techniques over the course of one year showed denitrification (99.0% N-loss in the winter and 85.0% N-loss in the summer) predominated over anammox (1.0% N-loss in the winter and 14.4% N-loss in the summer) and n-damo (0.6% N-loss in the winter) in surface soils (0-20 cm). While below 20 cm depth, N-loss was dominated by anammox (79.4 ± 14.3% in the winter and 65.4 ± 12.5% in the summer) and n-damo was not detected. Phylogenetic analysis showed that Candidatus Brocadia anammoxidans dominated the anammox community in the surface soil and Candidatus Brocadia fulgida dominated below 20 cm depth. Dissimilatory nitrate reduction to ammonium (DNRA), another nitrite reduction process, was found to play a limited role (4.9 ± 3.5%) in the surface soil compared with denitrification; below 80 cm DNRA rates were much higher than rates of anammox and denitrification. Ammonium oxidation was the main source of NO2- above 80 cm (70.9 ± 23.3%), the key influencing factor on anammox rates, and nitrate reduction (100%) was the main NO2- source below 80 cm. Considering the anammox, n-damo and denitrification rates as a whole in the sampled soil profile, denitrification is still the main N-loss process in upland soils.}, } @article {pmid29528544, year = {2018}, author = {Kim, JS and Yamasaki, R and Song, S and Zhang, W and Wood, TK}, title = {Single cell observations show persister cells wake based on ribosome content.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14093}, pmid = {29528544}, issn = {1462-2920}, abstract = {Since persister cells survive antibiotic treatments through dormancy and resuscitate to reconstitute infections, it is imperative to determine the rate at which these cells revive. Using two sets of Escherichia coli persister cells, those arising after antibiotic treatment at low levels and those generated at high levels by ceasing transcription via rifampicin pretreatment (shown to be bona fide persisters through eight sets of experiments), we used microscopy of single cells to determine that the resuscitation of dormant persisters is heterogeneous and includes cells that grow immediately. In all, five phenotypes were found during the observation of persister cells when fresh nutrients were added: (i) immediate division, (ii) immediate elongation followed by division, (iii) immediate elongation but no division, (iv) delayed elongation/division and (v) no growth. In addition, once cell division begins, the growth rate is that of exponential cells. Critically, the greater the ribosome content, the faster the persister cells resuscitate.}, } @article {pmid29528542, year = {2018}, author = {Takahashi, K and Miyake, K and Hishiyama, S and Kamimura, N and Masai, E}, title = {Two novel decarboxylase genes play a key role in the stereospecific catabolism of dehydrodiconiferyl alcohol in Sphingobium sp. strain SYK-6.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1739-1750}, doi = {10.1111/1462-2920.14099}, pmid = {29528542}, issn = {1462-2920}, abstract = {Sphingobium sp. strain SYK-6 is able to use a phenylcoumaran-type biaryl, dehydrodiconiferyl alcohol (DCA), as a sole source of carbon and energy. In SYK-6 cells, the alcohol group of the B-ring side chain of DCA was first oxidized to the carboxyl group, and then the alcohol group of the A-ring side chain was oxidized to generate 5-(2-carboxyvinyl)-2-(4-hydroxy-3-methoxyphenyl)-7-methoxy-2,3-dihydrobenzofuran-3-carboxylate (DCA-CC). We identified phcF, phcG and phcH, which conferred the ability to convert DCA-CC into 3-(4-hydroxy-3-(4-hydroxy-3-methoxystyryl)-5-methoxyphenyl)acrylate (DCA-S) in a host strain. These genes exhibited no significant sequence similarity with known enzyme genes, whereas phcF and phcG, which contain a DUF3237 domain of unknown function, showed 32% amino acid sequence identity with each other. The DCA-CC conversion activities were markedly decreased by disruption of phcF and phcG, indicating that phcF and phcG play dominant roles in the conversion of DCA-CC. Purified PhcF and PhcG catalysed the decarboxylation of the A-ring side chain of DCA-CC, producing DCA-S, and showed enantiospecificity towards (+)- and (-)-DCA-CC respectively. PhcF and PhcG formed homotrimers, and their Km for DCA-CC were determined to be 84 μM and 103 μM, and Vmax were 307 μmol⋅min-1 ⋅mg-1 and 137 μmol⋅min-1 ⋅mg-1 respectively. In conclusion, PhcF and PhcG are enantiospecific decarboxylases involved in phenylcoumaran catabolism.}, } @article {pmid29528534, year = {2018}, author = {Yue, Q and Li, Y and Chen, L and Zhang, X and Liu, X and An, Z and Bills, GF}, title = {Genomics-driven discovery of a novel self-resistance mechanism in the echinocandin-producing fungus Pezicula radicicola.}, journal = {Environmental microbiology}, volume = {20}, number = {9}, pages = {3154-3167}, doi = {10.1111/1462-2920.14089}, pmid = {29528534}, issn = {1462-2920}, support = {31629001//National Natural Science Foundation of China (NSFC)/ ; 31741004//National Natural Science Foundation of China (NSFC)/ ; //Kay and Ben Fortson Endowment/ ; }, abstract = {The echinocandins are antifungal lipopeptides targeting fungi via noncompetitive inhibition of the β-1,3-d-glucan synthase FKS1 subunit. A novel echinocandin resistance mechanism involving an auxiliary copy of FKS1 in echinocandin-producing fungus Pezicula radicicola NRRL 12192 was discovered. We sequenced the genome of NRRL 12192 and predicted two FKS1-encoding genes (prfks1n and prfks1a), rather than a single FKS1 gene typical of filamentous ascomycetes. The prfks1a gene sits immediately adjacent to an echinocandin (sporiofungin) gene cluster, which was confirmed by disruption of prnrps4 and abolishment of sporiofungin production. Disruption of prfks1a dramatically increased the strain's sensitivity to exogenous echinocandins. In the absence of echinocandins, transcription levels of prfks1a relative to β-tubulin in the wild type and in Δprnrps4 stains were similar. Moreover, prfks1a is consistently transcribed at low levels and is upregulated in the presence of exogenous echinocandin, but not during growth conditions promoting endogenous production of sporiofungin. Therefore, we conclude that prfks1a is primarily responsible for protecting the fungus against extracellular echinocandin toxicity. The presence of unclustered auxiliary copies of FKS1 with high similarity to prfks1a in two other echinocandin-producing strains suggests that this previously unrecognized resistance mechanism may be common in echinocandin-producing fungi of the family Dermataceae of the class Leotiomycetes.}, } @article {pmid29528493, year = {2018}, author = {Renaud, S and Ledevin, R and Pisanu, B and Chapuis, JL and Quillfeldt, P and Hardouin, EA}, title = {Divergent in shape and convergent in function: Adaptive evolution of the mandible in Sub-Antarctic mice.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {878-892}, doi = {10.1111/evo.13467}, pmid = {29528493}, issn = {1558-5646}, abstract = {Convergent evolution in similar environments constitutes strong evidence of adaptive evolution. Transported with people around the world, house mice colonized even remote areas, such as Sub-Antarctic islands. There, they returned to a feral way of life, shifting towards a diet enriched in terrestrial macroinvertebrates. Here, we test the hypothesis that this triggered convergent evolution of the mandible, a morphological character involved in food consumption. Mandible shape from four Sub-Antarctic islands was compared to phylogeny, tracing the history of colonization, and climatic conditions. Mandible shape was primarily influenced by phylogenetic history, thus discarding the hypothesis of convergent evolution. The biomechanical properties of the jaw were then investigated. Incisor in-lever and temporalis out-lever suggested an increase in the velocity of incisor biting, in agreement with observations on various carnivorous and insectivorous rodents. The mechanical advantage related to incisor biting also revealed an increased functional performance in Sub-Antarctic populations, and appears to be an adaptation to catch prey more efficiently. The amount of change involved was larger than expected for a plastic response, suggesting microevolutionary processes were evolved. This study thus denotes some degree of adaptive convergent evolution related to changes in habitat-related changes in dietary items in Sub-Antarctic mice, but only regarding simple, functionally relevant aspects of mandible morphology.}, } @article {pmid29528491, year = {2018}, author = {Dhole, S and Stern, CA and Servedio, MR}, title = {Direct detection of male quality can facilitate the evolution of female choosiness and indicators of good genes: Evolution across a continuum of indicator mechanisms.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {770-784}, doi = {10.1111/evo.13466}, pmid = {29528491}, issn = {1558-5646}, abstract = {The evolution of mating displays as indicators of male quality has been the subject of extensive theoretical and empirical research for over four decades. Research has also addressed the evolution of female mate choice favoring such indicators. Yet, much debate still exists about whether displays can evolve through the indirect benefits of female mate choice. Here, we use a population genetic model to investigate how the extent to which females can directly detect male quality influences the evolution of female choosiness and male displays. We use a continuum framework that incorporates indicator mechanisms that are traditionally modeled separately. Counter to intuition, we find that intermediate levels of direct detection of male quality can facilitate, rather than impede, the evolution of female choosiness and male displays in broad regions of this continuum. We examine how this evolution is driven by selective forces on genetic quality and on the display, and find that direct detection of male quality results in stronger indirect selection favoring female choosiness. Our results imply that displays maybe more likely to evolve when female choosiness has already evolved to discriminate perceptible forms of male quality. They also highlight the importance of considering general female choosiness, as well as preference, in studies of "good genes."}, } @article {pmid29528428, year = {2018}, author = {Westbury, MV and Hartmann, S and Barlow, A and Wiesel, I and Leo, V and Welch, R and Parker, DM and Sicks, F and Ludwig, A and Dalén, L and Hofreiter, M}, title = {Extended and Continuous Decline in Effective Population Size Results in Low Genomic Diversity in the World's Rarest Hyena Species, the Brown Hyena.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1225-1237}, pmid = {29528428}, issn = {1537-1719}, abstract = {Hyenas (family Hyaenidae), as the sister group to cats (family Felidae), represent a deeply diverging branch within the cat-like carnivores (Feliformia). With an estimated population size of <10,000 individuals worldwide, the brown hyena (Parahyaena brunnea) represents the rarest of the four extant hyena species and has been listed as Near Threatened by the IUCN. Here, we report a high-coverage genome from a captive bred brown hyena and both mitochondrial and low-coverage nuclear genomes of 14 wild-caught brown hyena individuals from across southern Africa. We find that brown hyena harbor extremely low genetic diversity on both the mitochondrial and nuclear level, most likely resulting from a continuous and ongoing decline in effective population size that started ∼1 Ma and dramatically accelerated towards the end of the Pleistocene. Despite the strikingly low genetic diversity, we find no evidence of inbreeding within the captive bred individual and reveal phylogeographic structure, suggesting the existence of several potential subpopulations within the species.}, } @article {pmid29528411, year = {2018}, author = {Raymond-Bouchard, I and Goordial, J and Zolotarov, Y and Ronholm, J and Stromvik, M and Bakermans, C and Whyte, LG}, title = {Conserved genomic and amino acid traits of cold adaptation in subzero-growing Arctic permafrost bacteria.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy023}, pmid = {29528411}, issn = {1574-6941}, abstract = {Permafrost accounts for 27% of all soil ecosystems and harbors diverse microbial communities. Our understanding of microorganisms in permafrost, their activities and adaptations, remains limited. Using five subzero-growing (cryophilic) permafrost bacteria, we examined features of cold adaptation through comparative genomic analyses with mesophilic relatives. The cryophiles possess genes associated with cold adaptation, including cold shock proteins, RNA helicases, and oxidative stress and carotenoid synthesis enzymes. Higher abundances of genes associated with compatible solutes were observed, important for osmoregulation in permafrost brine veins. Most cryophiles in our study have higher transposase copy numbers than mesophiles. We investigated amino acid (AA) modifications in the cryophiles favoring increased protein flexibility at cold temperatures. Although overall there were few differences with the mesophiles, we found evidence of cold adaptation, with significant differences in proline, serine, glycine and aromaticity, in several cryophiles. The use of cold/hot AA ratios of >1, used in previous studies to indicate cold adaptation, was found to be inadequate on its own. Comparing the average of all cryophiles to all mesophiles, we found that overall cryophiles had a higher ratio of cold adapted proteins for serine (more serine), and to a lesser extent, proline and acidic residues (fewer prolines/acidic residues).}, } @article {pmid29528408, year = {2018}, author = {de Vries, S and von Dahlen, JK and Schnake, A and Ginschel, S and Schulz, B and Rose, LE}, title = {Broad-spectrum inhibition of Phytophthora infestans by fungal endophytes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, pmid = {29528408}, issn = {1574-6941}, abstract = {Phytophthora infestans is a devastating pathogen of tomato and potato. It readily overcomes resistance genes and applied agrochemicals and hence even today causes large yield losses. Fungal endophytes provide a largely unexplored avenue of control of Phy. infestans. Not only do endophytes produce a wide array of bioactive metabolites, they may also directly compete with and defeat pathogens in planta. Here, we tested 12 fungal endophytes isolated from different plant species in vitro for their production of metabolites with anti- Phytophthora activity. Four well-performing isolates were evaluated for their ability to suppress nine isolates of Phy. infestans on agar medium and in planta. Two endophytes reliably inhibited all Phy. infestans isolates on agar medium, of which Phoma eupatorii isolate 8082 was the most promising. It nearly abolished infection by Phy. infestans in planta. Our data indicate a role for the production of anti-Phytophthora compounds by the fungus and/or an enhanced plant defense response, as evident by an enhanced anthocyanin production. Here, we present a potential biocontrol agent, which can inhibit a broad-spectrum of Phy. infestans isolates. Such broadly acting inhibition is ideal, because it allows for effective control of genetically diverse isolates and may slow the adaptation of Phy. infestans.}, } @article {pmid29528404, year = {2018}, author = {Diao, M and Huisman, J and Muyzer, G}, title = {Spatio-temporal dynamics of sulfur bacteria during oxic--anoxic regime shifts in a seasonally stratified lake.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, pmid = {29528404}, issn = {1574-6941}, support = {322551//European Research Council/International ; }, abstract = {Sulfate-reducing bacteria (SRB) and sulfur-oxidizing bacteria drive major transformations in the sulfur cycle, and play vital roles in oxic--anoxic transitions in lakes and coastal waters. However, information on the succession of these sulfur bacteria in seasonally stratified lakes using molecular biological techniques is scarce. Here, we used 16S rRNA gene amplicon sequencing to study the spatio-temporal dynamics of sulfur bacteria during oxic--anoxic regime shifts in Lake Vechten. Oxygen and sulfate were mixed throughout the water column in winter and early spring. Meanwhile, SRB, green sulfur bacteria (GSB), purple sulfur bacteria (PSB), and colorless sulfur bacteria (CSB) exclusively inhabited the sediment. After the water column stratified, oxygen and nitrate concentrations decreased in the hypolimnion and various SRB species expanded into the anoxic hypolimnion. Consequently, sulfate was reduced to sulfide, stimulating the growth of PSB and GSB in the metalimnion and hypolimnion during summer stratification. When hypoxia spread throughout the water column during fall turnover, SRB and GSB vanished from the water column, whereas CSB (mainly Arcobacter) and PSB (Lamprocystis) became dominant and oxidized the accumulated sulfide under micro-aerobic conditions. Our results support the view that, once ecosystems have become anoxic and sulfidic, a large oxygen influx is needed to overcome the anaerobic sulfur cycle and bring the ecosystems back into their oxic state.}, } @article {pmid29527799, year = {2018}, author = {Kerney, RR and Hanken, J and Blackburn, DC}, title = {Early limb patterning in the direct-developing salamander Plethodon cinereus revealed by sox9 and col2a1.}, journal = {Evolution & development}, volume = {20}, number = {3-4}, pages = {100-107}, doi = {10.1111/ede.12250}, pmid = {29527799}, issn = {1525-142X}, mesh = {Animals ; Collagen Type II/*metabolism ; Extremities/embryology ; Phylogeny ; SOX9 Transcription Factor/*metabolism ; Urodela/*embryology/metabolism ; }, abstract = {Direct-developing amphibians form limbs during early embryonic stages, as opposed to the later, often postembryonic limb formation of metamorphosing species. Limb patterning is dramatically altered in direct-developing frogs, but little attention has been given to direct-developing salamanders. We use expression patterns of two genes, sox9 and col2a1, to assess skeletal patterning during embryonic limb development in the direct-developing salamander Plethodon cinereus. Limb patterning in P. cinereus partially resembles that described in other urodele species, with early formation of digit II and a generally anterior-to-posterior formation of preaxial digits. Unlike other salamanders described to date, differentiation of preaxial zeugopodial cartilages (radius/tibia) is not accelerated in relation to the postaxial cartilages, and there is no early differentiation of autopodial elements in relation to more proximal cartilages. Instead, digit II forms in continuity with the ulnar/fibular arch. This amniote-like connectivity to the first digit that forms may be a consequence of the embryonic formation of limbs in this direct-developing species. Additionally, and contrary to recent models of amphibian digit identity, there is no evidence of vestigial digits. This is the first account of gene expression in a plethodontid salamander and only the second published account of embryonic limb patterning in a direct-developing salamander species.}, } @article {pmid29527014, year = {2018}, author = {Wrighton, KH}, title = {Genetic engineering: Expanding the reach of Cas9.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {250-251}, pmid = {29527014}, issn = {1471-0064}, } @article {pmid29526806, year = {2018}, author = {Ma, XG and Sun, WG and Sun, H}, title = {Historical introgression among the species of Rodgersia (Saxifragaceae) in mountainous forests of southwest China.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {93-99}, doi = {10.1016/j.ympev.2018.03.002}, pmid = {29526806}, issn = {1095-9513}, mesh = {China ; DNA, Chloroplast/genetics ; *Ecosystem ; *Forests ; Genetic Variation ; Geography ; Haplotypes/genetics ; Phylogeny ; Probability ; Saxifragaceae/*genetics ; Species Specificity ; }, abstract = {In the present study, we used genetic data and ecological niche modelling to explore possible historical introgressions among the species of Rodgersia (Saxifragaceae) in central-southwest China. Markedly differentiated chloroplast haplotypes were found in R. aesculifolia, R. sambucifolia and the Lijiang (LJ) population of R. pinnata, respectively, and differentiated chloroplast haplotypes within each of them showed the closest relationships with haplotypes from different species. ITS cloning did not reveal any shared ribotype between R. aesculifolia and the remaining species. Historical introgression between R. aesculifolia and R. sambucifolia (or R. pinnata) seems to be the most plausible explanation according to the geographical pattern and derivative status of putative introgressed chloroplast haplotypes, and also from morphological evidence. Introgressions were also found among R. sambucifolia, R. pinnata, and R. henricii from Yunnan. Frequent gene exchanges may have promoted the diversity of leaf shapes in this genus. Ecological niche modelling indicated that past secondary contact following range shifts during Pleistocene cold periods may have provided opportunities for ancient introgression between R. aesculifolia and adjacent species.}, } @article {pmid29526805, year = {2018}, author = {Campbell, MA and Sado, T and Shinzato, C and Koyanagi, R and Okamoto, M and Miya, M}, title = {Multilocus phylogenetic analysis of the first molecular data from the rare and monotypic Amarsipidae places the family within the Pelagia and highlights limitations of existing data sets in resolving pelagian interrelationships.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {172-180}, doi = {10.1016/j.ympev.2018.03.008}, pmid = {29526805}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Fishes/*classification/*genetics ; *Genetic Loci ; Likelihood Functions ; *Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The Pelagia is a recently delineated group of fishes, comprising fifteen families formerly placed in six perciform suborders. The Pelagia was lately recognized as it encompasses huge morphological diversity and only in the last few years have large-scale molecular phylogenetic studies been undertaken that could unite such morphologically disparate lineages. Due to the recent erection of Pelagia, the composition of the taxon is not entirely certain. Five families of the former perciform suborder Stromateoidei have been identified as pelagians. However, the sixth stromateoid subfamily Amarsipidae is a rare monotypic family that has distinctive meristic and morphological characteristics from that of other stromateoids such as the lack of a pharyngeal sac. We examine molecular data generated from the sole species in Amarsipidae, Amarsipus carlsbergi, and demonstrate that it is clearly nested within Pelagia. As with two previous studies that have the breadth of sampling to evaluate pelagian intra-relationships, we find high support for monophyly of most family-level taxonomic units but statistical support for early-branching nodes in the pelagian tree is very low. We conduct the first analyses of Pelagia incorporating the multispecies coalescent and are limited by a high degree of missing loci, or, incomplete taxon sampling. The high degree of missing data across a complete sampling of pelagian lineages along with the deep time scale and rapid radiation of the lineage contribute to poor resolution of early-branching relationships within Pelagia that cannot be resolved with current data sets. Currently available data are either mitochondrial genomes or a super matrix of relatively few loci with a high degree of missing data. A new and independent dataset of numerous phylogenetic loci derived from high-throughput sequencing technology may reduce uncertainty within the Pelagia and provide insights into this adaptive radiation.}, } @article {pmid29526804, year = {2018}, author = {Marki, PZ and Fjeldså, J and Irestedt, M and Jønsson, KA}, title = {Molecular phylogenetics and species limits in a cryptically coloured radiation of Australo-Papuan passerine birds (Pachycephalidae: Colluricincla).}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {100-105}, doi = {10.1016/j.ympev.2018.02.029}, pmid = {29526804}, issn = {1095-9513}, mesh = {Animals ; Australia ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Geography ; Passeriformes/*classification/genetics ; Phenotype ; *Phylogeny ; Pigmentation/*genetics ; Species Specificity ; Time Factors ; }, abstract = {Detailed knowledge of species limits is an essential component of the study of biodiversity. Although accurate species delimitation usually requires detailed knowledge of both genetic and phenotypic variation, such variation may be limited or unavailable for some groups. In this study, we reconstruct a molecular phylogeny for all currently recognized species and subspecies of Australasian shrikethrushes (Colluricincla), including the first sequences of the poorly known C. tenebrosa. Using a novel method for species delimitation, the multi-rate Poisson Tree Process (mPTP), in concordance with the phylogenetic data, we estimate species limits in this genetically diverse, but phenotypically subtly differentiated complex of birds. In line with previous studies, we find that one species, the little shrikethrush (C. megarhyncha) is characterized by deep divergences among populations. Delimitation results suggest that these clades represent distinct species and we consequently propose a new classification. Furthermore, our findings suggest that C. megarhyncha melanorhyncha of Biak Island does not belong in this genus, but is nested within the whistlers (Pachycephala) as sister to P. phaionota. This study represents a useful example of species delimitation when phenotypic variation is limited or poorly defined.}, } @article {pmid29526494, year = {2018}, author = {Jones, ED}, title = {Ancient DNA: a history of the science before Jurassic Park.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {68-69}, number = {}, pages = {1-14}, doi = {10.1016/j.shpsc.2018.02.001}, pmid = {29526494}, issn = {1879-2499}, mesh = {Animals ; *DNA, Ancient ; Extinction, Biological ; *Fossils ; Genetics/*history ; History, 20th Century ; Invertebrates/genetics ; Plants/genetics ; Vertebrates/genetics ; }, } @article {pmid29526404, year = {2018}, author = {Amir, A and Balaban, NQ}, title = {Learning from Noise: How Observing Stochasticity May Aid Microbiology.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {376-385}, doi = {10.1016/j.tim.2018.02.003}, pmid = {29526404}, issn = {1878-4380}, abstract = {For many decades, the wedding of quantitative data with mathematical modeling has been fruitful, leading to important biological insights. Here, we review some of the ongoing efforts to gain insights into problems in microbiology - and, in particular, cell-cycle progression and its regulation - through observation and quantitative analysis of the natural fluctuations in the system. We first illustrate this idea by reviewing a classic example in microbiology - the Luria-Delbrück experiment - and discussing how, in that case, useful information was obtained by looking beyond the mean outcome of the experiment, but instead paying attention to the variability between replicates of the experiment. We then switch gears to the contemporary problem of cell cycle progression and discuss in more detail how insights into cell size regulation and, when relevant, coupling between the cell cycle and the circadian clock, can be gained by studying the natural fluctuations in the system and their statistical properties. We end with a more general discussion of how (in this context) the correct level of phenomenological model should be chosen, as well as some of the pitfalls associated with this type of analysis. Throughout this review the emphasis is not on providing details of the experimental setups or technical details of the models used, but rather, in fleshing out the conceptual structure of this particular approach to the problem. For this reason, we choose to illustrate the framework on a rather broad range of problems, and on organisms from all domains of life, to emphasize the commonality of the ideas and analysis used (as well as their differences).}, } @article {pmid29526403, year = {2018}, author = {Carson, JP and Ramm, GA and Robinson, MW and McManus, DP and Gobert, GN}, title = {Schistosome-Induced Fibrotic Disease: The Role of Hepatic Stellate Cells.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {524-540}, doi = {10.1016/j.pt.2018.02.005}, pmid = {29526403}, issn = {1471-5007}, mesh = {Hepatic Stellate Cells/*parasitology ; Humans ; Liver/parasitology ; Liver Cirrhosis/*etiology ; Research/trends ; Schistosomiasis/*complications ; }, abstract = {Hepatic fibrosis is a common pathology in various liver diseases. Hepatic stellate cells (HSCs) are the main cell type responsible for collagen deposition and fibrosis formation in the liver. Schistosomiasis is characterised by granulomatous fibrosis around parasite eggs trapped within the liver and other host tissues. This response is facilitated by the recruitment of immune cells and the activation of HSCs. The interactions between HSCs and schistosome eggs are complex and diverse, and a better understanding of these interactions could lead to improved resolution of fibrotic liver disease, including that associated with schistosomiasis. Here, we discuss recent advances in HSC biology and the role of HSCs in hepatic schistosomiasis.}, } @article {pmid29526402, year = {2018}, author = {Wilke, ABB and Beier, JC and Benelli, G}, title = {Transgenic Mosquitoes - Fact or Fiction?.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {456-465}, doi = {10.1016/j.pt.2018.02.003}, pmid = {29526402}, issn = {1471-5007}, support = {U01 CK000510/CK/NCEZID CDC HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Culicidae/*genetics ; Mosquito Control/*methods/standards/trends ; Risk Assessment ; World Health Organization ; }, abstract = {Technologies for controlling mosquito vectors based on genetic manipulation and the release of genetically modified mosquitoes (GMMs) are gaining ground. However, concrete epidemiological evidence of their effectiveness, sustainability, and impact on the environment and nontarget species is lacking; no reliable ecological evidence on the potential interactions among GMMs, target populations, and other mosquito species populations exists; and no GMM technology has yet been approved by the WHO Vector Control Advisory Group. Our opinion is that, although GMMs may be considered a promising control tool, more studies are needed to assess their true effectiveness, risks, and benefits. Overall, several lines of evidence must be provided before GMM-based control strategies can be used under the integrated vector management framework.}, } @article {pmid29526401, year = {2018}, author = {Vannatta, JT and Minchella, DJ}, title = {Parasites and Their Impact on Ecosystem Nutrient Cycling.}, journal = {Trends in parasitology}, volume = {34}, number = {6}, pages = {452-455}, doi = {10.1016/j.pt.2018.02.007}, pmid = {29526401}, issn = {1471-5007}, mesh = {Animals ; *Ecosystem ; Host-Parasite Interactions ; Models, Biological ; Parasites/*physiology ; }, abstract = {Consumer species alter nutrient cycling through nutrient transformation, transfer, and bioturbation. Parasites have rarely been considered in this framework despite their ability to indirectly alter the cycling of nutrients via their hosts. A simple mathematical framework can be used to assess the relative importance of parasite-derived nutrients in an ecosystem.}, } @article {pmid29526400, year = {2018}, author = {}, title = {Loa loa: More Than Meets the Eye?.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {261-263}, doi = {10.1016/j.pt.2018.02.002}, pmid = {29526400}, issn = {1471-5007}, mesh = {Animals ; Humans ; Loa/physiology ; Loiasis/epidemiology/*prevention & control ; *Models, Theoretical ; }, } @article {pmid29525488, year = {2018}, author = {Nackley, LL and West, AG and Skowno, AL and Bond, WJ}, title = {Questioning the Alienation of Native Species from Invasion Ecology: A Reply to Tong et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {235-236}, doi = {10.1016/j.tree.2018.02.001}, pmid = {29525488}, issn = {1872-8383}, } @article {pmid29525438, year = {2018}, author = {}, title = {How Do You Design Undergraduate Genetics Laboratory Courses?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {247-249}, doi = {10.1016/j.tig.2018.02.001}, pmid = {29525438}, issn = {0168-9525}, mesh = {Adult ; Curriculum ; Faculty/*education ; Female ; Genetics/*education ; Humans ; Male ; Research/*education ; Universities ; }, } @article {pmid29525421, year = {2018}, author = {Sun, J and Zhang, H and Liu, YH and Feng, Y}, title = {Towards Understanding MCR-like Colistin Resistance.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {794-808}, doi = {10.1016/j.tim.2018.02.006}, pmid = {29525421}, issn = {1878-4380}, abstract = {Antibiotic resistance has become a global public health priority. Polymyxins, a family of cationic polypeptide antibiotics, act as a final line of refuge against severe infections by Gram-negative pathogens with pan-drug resistance. Unfortunately, this last-resort antibiotic has been challenged by the emergence and global spread of mobilized colistin resistance determinants (mcr). Given the fact that it has triggered extensive concerns worldwide, we present here an updated view of MCR-like colistin resistance. These studies provide a basic framework for understanding the molecular epidemiology and resistance mechanism of MCR-like genes. However, further large-scale epidemiology and functional studies are urgently needed to better understand the biology of this clinically important antibiotic resistance.}, } @article {pmid29524653, year = {2018}, author = {Zhang, JM and López-Pujol, J and Gong, X and Wang, HF and Vilatersana, R and Zhou, SL}, title = {Population genetic dynamics of Himalayan-Hengduan tree peonies, Paeonia subsect. Delavayanae.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {62-77}, doi = {10.1016/j.ympev.2018.03.003}, pmid = {29524653}, issn = {1095-9513}, mesh = {Bayes Theorem ; Ecosystem ; Genetic Markers ; Genetic Variation ; *Genetics, Population ; Microsatellite Repeats ; Paeonia/*genetics ; Phylogeny ; Phylogeography ; Population Dynamics ; Principal Component Analysis ; Trees/*genetics ; }, abstract = {According to the present taxonomical treatment, Paeonia subsect. Delavayanae consists of only two species (P. delavayi and P. ludlowii) endemic to the Himalayan-Hengduan Mountains. Although P. ludlowii can be distinguished from P. delavayi on the basis of a series of morphological characters, the species delimitation remains controversial because the more widespread one, P. delavayi, exhibits considerable morphological diversity. Both chloroplast DNA markers and nuclear microsatellites or simple sequence repeats (nSSR) are used herein to reveal genetic diversity and relationships of the two taxa included in this subsection, and ecological niche modeling (ENM) is employed to get insights into their paleodistribution. Our results show that genetic boundaries between the two currently recognized species are unclear, probably due to recent divergence. Paeonia ludlowii is budding from P. delavayi, probably by genetic isolation but also by shifting its niche to the harsher upland Tibetan conditions. Paeonia delavayi itself would be, however, under active speciation, showing significant genetic differentiation and morphological diversity. Whereas P. ludlowii would have endured the Pleistocene glacial periods by in situ persistence in local, small refugia, a 'dual' model seems to apply for P. delavayi (in situ persistence and retreat to refugia). The rarity of P. ludlowii and high evolutionary potential of P. delavayi imply high priority for in situ conservation of both taxa. The Himalayan-Hengduan Mountains are an ideal arena for differentiation within subsect. Delavayanae of Paeonia, by means of expansions/contractions/displacements, vertical migrations, and local survival/extinctions in response to the Neogene climate fluctuations and geological changes.}, } @article {pmid29524652, year = {2018}, author = {Berriman, JS and Ellingson, RA and Awbrey, JD and Rico, DM and Valdés, ÁA and Wilson, NG and Aguilar, A and Herbert, DG and Hirano, YM and Trowbridge, CD and Krug, PJ}, title = {A biting commentary: Integrating tooth characters with molecular data doubles known species diversity in a lineage of sea slugs that consume "killer algae".}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {356-370}, pmid = {29524652}, issn = {1095-9513}, support = {R25 GM061331/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; Biodiversity ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/genetics ; Eukaryota/*physiology ; Gastropoda/*physiology ; Genetic Variation ; Haplotypes/genetics ; Mitochondria/genetics ; *Phylogeny ; Species Specificity ; Tooth/*physiology ; }, abstract = {Predicting biotic resistance to highly invasive strains of "killer algae" (Caulerpa spp.) requires understanding the diversity and feeding preferences of native consumers, including sea slugs in family Oxynoidae. Past studies reported low algal host specificity for Oxynoe (6 spp.) and Lobiger (4 spp.), but these taxonomically challenging slugs may represent species complexes of unrecognized specialists that prefer different Caulerpa spp. Here, we assess global diversity of these genera by integrating gene sequences with morphological data from microscopic teeth and internal shells, the only hard parts in these soft-bodied invertebrates. Four delimitation methods applied to datasets comprising mtDNA and/or nuclear alleles yielded up to 16 species hypotheses for samples comprising five nominal taxa, including five highly divergent species in Lobiger and five in Oxynoe. Depending on the analysis, a further four to six species were recovered in the O. antillarum-viridis complex, a clade in which mitochondrial divergence was low and nuclear alleles were shared among lineages. Bayesian species delimitation using only morphological data supported most candidate species, however, and integrative analyses combining morphological and genetic data fully supported all complex members. Collectively, our findings double the recognized biodiversity in Oxynoidae, and illustrate the value of including data from traits that mediate fast-evolving ecological interactions during species delimitation. Preference for Caulerpa spp. and radular tooth characteristics covaried among newly delimited species, highlighting an unappreciated degree of host specialization and coevolution in these taxa that may help predict their role in containing outbreaks of invasive algae.}, } @article {pmid29524651, year = {2018}, author = {Kim, S and de Medeiros, BAS and Byun, BK and Lee, S and Kang, JH and Lee, B and Farrell, BD}, title = {West meets East: How do rainforest beetles become circum-Pacific? Evolutionary origin of Callipogon relictus and allied species (Cerambycidae: Prioninae) in the New and Old Worlds.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {163-176}, doi = {10.1016/j.ympev.2018.02.019}, pmid = {29524651}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Coleoptera/classification/*genetics ; *Evolution, Molecular ; Fossils ; Phylogeny ; Phylogeography ; *Rainforest ; Species Specificity ; Time Factors ; }, abstract = {The longhorn beetle genus Callipogon Audinet-Serville represents a small group of large wood-boring beetles whose distribution pattern exhibits a unique trans-Pacific disjunction between the East Asian temperate rainforest and the tropical rainforest of the Neotropics. To understand the biogeographic history underlying this circum-Pacific disjunct distribution, we reconstructed a molecular phylogeny of the subfamily Prioninae with extensive sampling of Callipogon using multilocus sequence data of 99 prionine and four parandrine samples (ingroups), together with two distant outgroup species. Our sampling of Callipogon includes 18 of the 24 currently accepted species, with complete representation of all species in our focal subgenera. Our phylogenetic analyses confirmed the purported affinity between the Palearctic Callipogon relictus and its Neotropical congeners. Furthermore, based on molecular dating under the fossilized birth-death (FBD) model with comprehensive fossil records and probabilistic ancestral range reconstructions, we estimated the crown group Callipogon to have originated in the Paleocene circa 60 million years ago (Ma) across the Neotropics and Eastern Palearctics. The divergence between the Palearctic C. relictus and its Neotropical congeners is explained as the result of a vicariance event following the demise of boreotropical forest across Beringia at the Eocene-Oligocene boundary. As C. relictus represents the unique relictual species that evidentiates the lineage's expansive ancient distribution, we evaluated its conservation importance through species distribution modelling. Though we estimated a range expansion for C. relictus by 2050, we emphasize a careful implementation of conservation programs towards the protection of primary forest across its current habitats, as the species remains highly vulnerable to habitat disturbance.}, } @article {pmid29524434, year = {2018}, author = {Iwasaki, M and Kuroda, J and Kawakami, K and Wada, H}, title = {Epidermal regulation of bone morphogenesis through the development and regeneration of osteoblasts in the zebrafish scale.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {105-119}, doi = {10.1016/j.ydbio.2018.03.005}, pmid = {29524434}, issn = {1095-564X}, mesh = {Animals ; Body Patterning/genetics ; Bone Development/*genetics/physiology ; Epidermis/*metabolism ; Gene Expression Regulation, Developmental ; Hedgehog Proteins/metabolism ; Immunohistochemistry ; In Situ Hybridization ; Osteoblasts/*cytology/physiology ; Regeneration/*genetics/physiology ; Signal Transduction ; Wnt Signaling Pathway/physiology ; Zebrafish/genetics ; Zebrafish Proteins/genetics/metabolism ; }, abstract = {Bone is a connective tissue composed of many cell types, including osteoblasts. How bones acquire their unique size and shape during development remains poorly understood. Herein we investigated the molecular and cellular mechanisms of bone morphogenesis in the zebrafish scale by using transgenic lines to enable visualization of specific types of osteoblasts. We demonstrate that the zebrafish scale contains three distinct types of osteoblasts: (i) a monolayer of central osteoblasts along the inner surface of scales; (ii) marginal osteoblasts elongated along the scale edge; and (iii) submarginal osteoblasts located between the central and marginal osteoblast populations. The size of the central osteoblasts increases progressively during development, suggesting that scale growth is mediated primarily by cell growth rather than the recruitment of new osteoblasts. In addition, the total number of central osteoblasts increases in regenerated scales and is correlated with scale size, possibly allowing for the rapid growth of regenerating scales. Moreover, osteoblast proliferation is not detected during regeneration, suggesting that the osteoblasts originate from post-mitotic precursor cells. Sonic hedgehog a (shha) is expressed in the epidermal cells that make contact with the marginal osteoblasts. Pharmacological inhibition of Hedgehog (Hh) signaling during regeneration reduces the number of marginal osteoblasts and interferes with scale growth, indicating that epidermis-derived Shh regulates scale regeneration. Finally, genetic inhibition of Wnt/planar cell polarity (PCP) signaling in the epidermis results in misorientation of scales with regard to the body axis. These results reveal a novel role for the epidermis in the regulation of bone patterning, namely the regeneration of osteoblasts and directional bone growth.}, } @article {pmid29524217, year = {2018}, author = {Saporito, RA and Grant, T}, title = {Comment on Amézquita et al. (2017) "Conspicuousness, color resemblance, and toxicity in geographically diverging mimicry: The pan-Amazonian frog Allobates femoralis".}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {1009-1014}, doi = {10.1111/evo.13468}, pmid = {29524217}, issn = {1558-5646}, abstract = {Amézquita et al. (2017) recently concluded that species of the Allobates femoralis group are toxic to mice at levels equivalent to syntopic alkaloid-containing poison frogs, which they attributed to the presence of alkaloids in skin secretions. However, the chemical composition of skin secretions was not analyzed, and here we present additional data supporting the absence of alkaloids in skin secretions of the Allobates femoralis group. Instead, we suggest the observed toxicity was caused by the anesthetic benzocaine, which was applied to the buccal cavity to euthanize frogs prior to skin removal. We show that orally administered benzocaine is rapidly incorporated into the skin of species that sequester and do not sequester alkaloids, which casts doubt on the conclusion that Allobates femoralis group skin secretions are toxic and makes the results of experiments with alkaloid-containing species of Adelphobates and Ameerega uninterpretable. To prevent experimental errors and misinterpretations in studies of amphibian chemical defense, we encourage researchers to test the chemical composition of samples prior to experimentation, include all necessary controls to detect false positives, conduct small pilot studies for new methods, and consider the limitations of particular methods and their ability to address the intended research questions.}, } @article {pmid29524007, year = {2018}, author = {Xavier, C and Soares, RVS and Amorim, IC and Cabral-de-Mello, DC and de Cássia de Moura, R}, title = {Insights into the karyotype evolution and speciation of the beetle Euchroma gigantea (Coleoptera: Buprestidae).}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {3}, pages = {163-178}, pmid = {29524007}, issn = {1573-6849}, support = {0777-2.02/15//Fundação de Amparo à Ciência e Tecnologia do Estado de Pernambuco/International ; 2014/11763-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 305298/2014-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; }, mesh = {Animals ; Chromosomes, Insect/*genetics ; Coleoptera/*genetics ; *Evolution, Molecular ; *Karyotype ; }, abstract = {Euchroma Dejean, 1833 (Buprestidae: Coleoptera) is a monotypic genus comprising the species Euchroma gigantea, with populations presenting a degree of karyotypic variation/polymorphism rarely found within a single taxonomic (specific) unit, as well as drastically incompatible meiotic configurations in populations from extremes of the species range. To better understand the complex karyotypic evolution of E. gigantea, the karyotypes of specimens from five populations in Brazil were investigated using molecular cytogenetics and phylogenetic approaches. Herein, we used FISH with histone genes as well as sequencing of the COI to determine differential distribution of markers and relationships among populations. The analyses revealed new karyotypes, with variability for chromosome number and morphology of multiple sex chromosome mechanisms, occurrence of B chromosome variants (punctiform and large ones), and high dispersion of histone genes in different karyotypes. These data indicate that chromosomal polymorphism in E. gigantea is greater than previously reported, and that the species can be a valuable model for cytogenetic studies. The COI phylogenetic and haplotype analyses highlighted the formation of three groups with chromosomally polymorphic individuals. Finally, we compared the different karyotypes and proposed a model for the chromosomal evolution of this species. The species E. gigantea includes at least three cytogenetically polymorphic lineages. Moreover, in each of these lineages, different chromosomal rearrangements have been fixed. Dispersion of repetitive sequences may have favored the high frequency of these rearrangements, which could be related to both adaptation of the species to different habitats and the speciation process.}, } @article {pmid29523910, year = {2018}, author = {Ripabelli, G and Tamburro, M and Guerrizio, G and Fanelli, I and Flocco, R and Scutellà, M and Sammarco, ML}, title = {Tracking Multidrug-Resistant Klebsiella pneumoniae from an Italian Hospital: Molecular Epidemiology and Surveillance by PFGE, RAPD and PCR-Based Resistance Genes Prevalence.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {977-987}, pmid = {29523910}, issn = {1432-0991}, mesh = {Adult ; Aged ; Aged, 80 and over ; Anti-Bacterial Agents/*pharmacology ; Carbapenems/pharmacology ; DNA, Bacterial/genetics ; Drug Resistance, Multiple, Bacterial/*genetics ; Electrophoresis, Gel, Pulsed-Field ; Female ; Humans ; Infant, Newborn ; Intensive Care Units/statistics & numerical data ; Italy/epidemiology ; Klebsiella Infections/drug therapy/*epidemiology/microbiology ; Klebsiella pneumoniae/*drug effects/*genetics ; Male ; Microbial Sensitivity Tests ; Middle Aged ; Molecular Epidemiology ; Polymerase Chain Reaction ; Random Amplified Polymorphic DNA Technique ; Young Adult ; beta-Lactamases/genetics ; }, abstract = {Antimicrobial-resistant Klebsiella pneumoniae represent a global public health concern. K. pneumoniae strains isolated during 2010 and 2014-2016 within a single hospital of Molise Region, Central Italy, were analyzed testing antimicrobial susceptibility, clonality by pulsed-field gel electrophoresis (PFGE) and random amplified polymorphic DNA (RAPD)-PCR, and prevalence of carbapenem resistance genes by PCR. Forty isolates (23 wild-type in 2010 and 17 non-wild-type in 2014-2016) were collected from hospitalized patients (65.2 ± 18.1 years old, 75% male, 80% from intensive care unit-ICU). K. pneumoniae showed multidrug-resistant profiles and 15 resistotypes were identified (discriminatory power D = 0.88). The 69.6 and 17.4% of isolates in 2010 resulted intermediate and resistant to imipenem, respectively, and 91.3% was sensitive to meropenem, while 88.2% of isolates of 2014-2016 were resistant to both antibiotics. PFGE identified 16 clusters versus 23 by RAPD, 26 pulsotypes versus 33 RAPD patterns (D ≥ 0.97). PFGE separated strains according to isolation period and identified an outbreak occurred in the ICU during December 2014 and January 2015. No strains harbored blaGES, blaIMP, blaNDM-1, and blaOXA-48 genes, as well as AmpC plasmid-mediated beta-lactamases genes. Only K. pneumoniae isolated during 2014-2016 were blaKPC positive. Prevalence of blaVIM was 87 and 76.5% during 2010 and 2014-2016, respectively. No strains colistin-resistant harbored mcr-1 plasmid-mediated resistance gene. The study findings underline an increased circulation of multidrug-resistant K. pneumoniae within the hospital, and the acquisition of carbapenem resistance mechanism. The implementation of surveillance and molecular characterization of isolates are needed to identify outbreaks, reduce the spread of resistance, and guide empirical therapy.}, } @article {pmid29523710, year = {2018}, author = {Hearty, PJ and Tormey, BR}, title = {Listen to the whisper of the rocks, telling their ancient story.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2902-E2903}, pmid = {29523710}, issn = {1091-6490}, } @article {pmid29523709, year = {2018}, author = {Rovere, A and Casella, E and Harris, DL and Lorscheid, T and Nandasena, NAK and Dyer, B and Sandstrom, MR and Stocchi, P and D'Andrea, WJ and Raymo, ME}, title = {Reply to Hearty and Tormey: Use the scientific method to test geologic hypotheses, because rocks do not whisper.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2904-E2905}, pmid = {29523709}, issn = {1091-6490}, } @article {pmid29523708, year = {2018}, author = {Astumian, RD}, title = {Stochastically pumped adaptation and directional motion of molecular machines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9405-9413}, pmid = {29523708}, issn = {1091-6490}, abstract = {Recent developments in synthetic molecular motors and pumps have sprung from a remarkable confluence of experiment and theory. Synthetic accomplishments have facilitated the ability to design and create molecules, many of them featuring mechanically bonded components, to carry out specific functions in their environment-walking along a polymeric track, unidirectional circling of one ring about another, synthesizing stereoisomers according to an external protocol, or pumping rings onto a long rod-like molecule to form and maintain high-energy, complex, nonequilibrium structures from simpler antecedents. Progress in the theory of nanoscale stochastic thermodynamics, specifically the generalization and extension of the principle of microscopic reversibility to the single-molecule regime, has enhanced the understanding of the design requirements for achieving strong unidirectional motion and high efficiency of these synthetic molecular machines for harnessing energy from external fluctuations to carry out mechanical and/or chemical functions in their environment. A key insight is that the interaction between the fluctuations and the transition state energies plays a central role in determining the steady-state concentrations. Kinetic asymmetry, a requirement for stochastic adaptation, occurs when there is an imbalance in the effect of the fluctuations on the forward and reverse rate constants. Because of strong viscosity, the motions of the machine can be viewed as mechanical equilibrium processes where mechanical resonances are simply impossible but where the probability distributions for the state occupancies and trajectories are very different from those that would be expected at thermodynamic equilibrium.}, } @article {pmid29523707, year = {2018}, author = {Davies, KM and Kühlbrandt, W}, title = {Structure of the catalytic F1 head of the F1-Fo ATP synthase from Trypanosoma brucei.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2906-E2907}, pmid = {29523707}, issn = {1091-6490}, mesh = {Adenosine Triphosphate ; Catalysis ; Mitochondria ; *Proton-Translocating ATPases ; *Trypanosoma brucei brucei ; }, } @article {pmid29523393, year = {2018}, author = {Martiny, JBH and Walters, KE}, title = {Towards a Natural History of Soil Bacterial Communities.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {250-252}, doi = {10.1016/j.tim.2018.02.010}, pmid = {29523393}, issn = {1878-4380}, abstract = {Despite the enormous diversity of bacteria, a recent study reveals that soils are globally dominated by a small list of taxa. Characterizing the traits of these bacteria offers the potential for predicting functional differences among soil communities.}, } @article {pmid29523192, year = {2018}, author = {Pita, L and Rix, L and Slaby, BM and Franke, A and Hentschel, U}, title = {The sponge holobiont in a changing ocean: from microbes to ecosystems.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {46}, pmid = {29523192}, issn = {2049-2618}, support = {679849//Horizon 2020/International ; 679849//Horizon 2020/International ; CRC1182-TPB1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Animals ; Aquatic Organisms/microbiology ; Bacteria/*metabolism ; Carbon/metabolism ; Climate Change ; Dysbiosis/*pathology ; Ecosystem ; Microbiota/*physiology ; Nitrogen/metabolism ; Oceans and Seas ; Phosphorus/metabolism ; Porifera/*metabolism/*microbiology ; Symbiosis/*physiology ; }, abstract = {The recognition that all macroorganisms live in symbiotic association with microbial communities has opened up a new field in biology. Animals, plants, and algae are now considered holobionts, complex ecosystems consisting of the host, the microbiota, and the interactions among them. Accordingly, ecological concepts can be applied to understand the host-derived and microbial processes that govern the dynamics of the interactive networks within the holobiont. In marine systems, holobionts are further integrated into larger and more complex communities and ecosystems, a concept referred to as "nested ecosystems." In this review, we discuss the concept of holobionts as dynamic ecosystems that interact at multiple scales and respond to environmental change. We focus on the symbiosis of sponges with their microbial communities-a symbiosis that has resulted in one of the most diverse and complex holobionts in the marine environment. In recent years, the field of sponge microbiology has remarkably advanced in terms of curated databases, standardized protocols, and information on the functions of the microbiota. Like a Russian doll, these microbial processes are translated into sponge holobiont functions that impact the surrounding ecosystem. For example, the sponge-associated microbial metabolisms, fueled by the high filtering capacity of the sponge host, substantially affect the biogeochemical cycling of key nutrients like carbon, nitrogen, and phosphorous. Since sponge holobionts are increasingly threatened by anthropogenic stressors that jeopardize the stability of the holobiont ecosystem, we discuss the link between environmental perturbations, dysbiosis, and sponge diseases. Experimental studies suggest that the microbial community composition is tightly linked to holobiont health, but whether dysbiosis is a cause or a consequence of holobiont collapse remains unresolved. Moreover, the potential role of the microbiome in mediating the capacity for holobionts to acclimate and adapt to environmental change is unknown. Future studies should aim to identify the mechanisms underlying holobiont dynamics at multiple scales, from the microbiome to the ecosystem, and develop management strategies to preserve the key functions provided by the sponge holobiont in our present and future oceans.}, } @article {pmid29523189, year = {2018}, author = {Ralapanawa, U and Jayalath, T and Senadhira, D}, title = {A case of acute necrotizing pancreatitis complicated with non ST elevation myocardial infarction.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {167}, pmid = {29523189}, issn = {1756-0500}, mesh = {Female ; Humans ; Middle Aged ; Myocardial Infarction/*diagnosis ; Pancreatitis, Acute Necrotizing/*diagnosis ; }, abstract = {BACKGROUND: Acute pancreatitis is an inflammatory condition with varying severity and a range of local and systemic complications. Here we report a patient with acute necrotizing pancreatitis complicated with a true non ST elevation myocardial infarction.

CASE PRESENTATION: A 58 year old lady was admitted to our unit with acute onset epigastric pain and vomiting for 4 h duration. Following admission she complained of retrosternal tightening type of a chest pain. She had elevated serum amylase and cardiac troponin. Electrocardiogram (ECG) revealed lateral ischaemia. Contrast computerized tomography abdomen revealed acute severe necrotizing pancreatitis.

CONCLUSIONS: Nonspecific ECG changes can occur in patients with acute pancreatitis. But the diagnosis of true myocardial infarction in a context of acute pancreatitis using ECGs, 2D echocardiography, cardiac biomarkers and coronary angiograms can be challenging with the choice of revascularization therapy and safety of antiplatelet agents and anticoagulant therapy. Decision making regarding the management of such a patient is also critical.}, } @article {pmid29523179, year = {2018}, author = {Ralapanawa, DMPUK and Kumarihamy, KWMPP and Sundararajah, M and Jayalath, WATA}, title = {A young female presenting with heart failure secondary to eosinophilic myocarditis: a case report and review of the literature.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {168}, pmid = {29523179}, issn = {1756-0500}, mesh = {Adult ; Eosinophilia/*complications ; Female ; Heart Failure/*etiology ; Humans ; Myocarditis/*complications ; Young Adult ; }, abstract = {BACKGROUND: Eosinophilic myocarditis is one of the fatal complications of idiopathic hypereosinophilic syndromes. Given the rarity of this form of myocarditis, it is often under-recognized. We describe a young girl who presented with features of heart failure. To our knowledge, this is the first reported case of eosinophilic myocarditis in a young Sri Lankan female.

CASE PRESENTATION: A previously healthy 21 year old Sri Lankan female admitted with shortness of breath for 1 week duration with associated low grade fever and profuse sweating. She was mildly febrile and dyspnoeic with absent ankle oedema. She was tachycardic and had elevated Jugular venous pressure with negative Kussmaul sign. Blood pressure was 100/70 mmHg. Clinically there was no cardiomegaly and heart sounds were slightly muffled with gallop rhythm. Bilateral basal fine end inspiratory crackles and mild hepatosplenomegaly were noted. The laboratory examinations showed leucocytosis with severe eosinophilia with no abnormal cells. Her ESR, Troponin I and Brain natriuretic peptide were elevated with normal CRP and electrocardiogram showed sinus tachycardia with wide spread ST depression. Heart failure was evident on chest X-ray and 2D-echocardiogram showed global left ventricular hypokinesia with 40% ejection fraction and a thin layer of pericardial effusion. Mild hepatosplenomegaly without lymphadenopathy was detected in the ultrasound scan. Bone marrow biopsy showed hypereosinophilia with no evidence of bone marrow infiltration. FIP1L1-PDGFRA fusion transcript and BCR-ABL transcript were not detected. Secondary causes for hypereosinophilia were excluded and the diagnosis of idiopathic hypereosinophilic syndrome and eosinophilic myocarditis was made. She had good response to steroids clinically and biochemically with complete recovery of left ventricular function. She is now on steroid to be continued at least 6 months to 1 year.

CONCLUSION: Eosinophilic myocarditis is a rare but fatal disease if left untreated. Hence clinicians should have high index of suspicion to diagnose eosinophilic myocarditis in clinical context of heart failure due to myocarditis. The diagnoses of eosinophilic myocarditis may often be challenged especially in a poor recourse setting. However available investigation should be used to diagnose this condition without delay. Early treatment with systemic steroids may prevent fatal outcome and therapies for this disease have yet to be validated in large prospective studies.}, } @article {pmid29523096, year = {2018}, author = {Miersch, C and Stange, K and Röntgen, M}, title = {Separation of functionally divergent muscle precursor cell populations from porcine juvenile muscles by discontinuous Percoll density gradient centrifugation.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {2}, pmid = {29523096}, issn = {1471-2121}, mesh = {Animals ; Biomarkers/metabolism ; Cell Adhesion ; Cell Differentiation ; Cell Proliferation ; Cell Separation/*methods ; Cell Size ; Centrifugation, Density Gradient ; Muscle Development ; Muscle Fibers, Skeletal/cytology ; Muscle, Skeletal/*cytology ; Povidone ; Silicon Dioxide ; Stem Cells/*cytology ; Sus scrofa ; }, abstract = {BACKGROUND: Satellite cells (SC) and their descendants, muscle precursor cells (MPC), play a key role in postnatal muscle development, regeneration, and plasticity. Several studies have provided evidence that SC and MPC represent a heterogeneous population differing in their biochemical and functional properties. The identification and characterization of functionally divergent SC subpopulations should help to reveal the precise involvement of SC/MPC in these myogenic processes. The aim of the present work was therefore to separate SC subpopulations by using Percoll gradients and to characterize their myogenic marker profiles and their functional properties (adhesion, proliferation, and differentiation).

RESULTS: SC/MPC from muscles of 4-day-old piglets were isolated by trypsin digestion and enriched by Percoll density gradient centrifugation. A mixed myogenic cell population was obtained from the 40/70% interface (termed: mixed P40/70) of a 25/40/70% Percoll gradient. Thereafter, by using a more stepped 25/40/50/70% Percoll gradient, mixed P40/70 was divided into subpopulation 40/50 (SP40/50) collected from the 40/50% interface and subpopulation 50/70 (SP50/70) collected from the 50/70% interface. All three isolated populations proliferated and showed a myogenic phenotype characterized by the ability to express myogenic markers (Pax7, MyoD1, Desmin, and MyoG) and to differentiate into myotubes. However, compared with mixed P40/70, SP40/50 and SP50/70 exhibited distinct functional behavior. Growth kinetic curves over 90 h obtained by the xCELLigence system and proliferation assays revealed that SP40/50 and mixed P40/70 constituted a fast adhering and fast proliferating phenotype. In contrast, SP50/70 showed considerably slower adhesion and proliferation. The fast-proliferating SP40/50 showed the highest myogenic differentiation potential with higher fusion rates and the formation of more middle-sized and large myotubes.

CONCLUSIONS: The described Percoll density gradient centrifugation represents a useful tool for subdividing pig SC/MPC populations with divergent myogenic functions. The physiological role of SC subpopulations during myogenesis and the interaction of these populations can now be analyzed to a greater extent, shedding light on postnatal growth variations in pigs and probably in other animals.}, } @article {pmid29523085, year = {2018}, author = {Govindaraj, RG and Brylinski, M}, title = {Comparative assessment of strategies to identify similar ligand-binding pockets in proteins.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {91}, pmid = {29523085}, issn = {1471-2105}, support = {R35 GM119524/GM/NIGMS NIH HHS/United States ; R35GM119524/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Amino Acid Sequence ; Area Under Curve ; Binding Sites ; Databases, Protein ; Drug Discovery ; Ligands ; Models, Molecular ; Protein Binding ; Protein Conformation ; Proteins/chemistry/*metabolism ; ROC Curve ; Sequence Alignment ; }, abstract = {BACKGROUND: Detecting similar ligand-binding sites in globally unrelated proteins has a wide range of applications in modern drug discovery, including drug repurposing, the prediction of side effects, and drug-target interactions. Although a number of techniques to compare binding pockets have been developed, this problem still poses significant challenges.

RESULTS: We evaluate the performance of three algorithms to calculate similarities between ligand-binding sites, APoc, SiteEngine, and G-LoSA. Our assessment considers not only the capabilities to identify similar pockets and to construct accurate local alignments, but also the dependence of these alignments on the sequence order. We point out certain drawbacks of previously compiled datasets, such as the inclusion of structurally similar proteins, leading to an overestimated performance. To address these issues, a rigorous procedure to prepare unbiased, high-quality benchmarking sets is proposed. Further, we conduct a comparative assessment of techniques directly aligning binding pockets to indirect strategies employing structure-based virtual screening with AutoDock Vina and rDock.

CONCLUSIONS: Thorough benchmarks reveal that G-LoSA offers a fairly robust overall performance, whereas the accuracy of APoc and SiteEngine is satisfactory only against easy datasets. Moreover, combining various algorithms into a meta-predictor improves the performance of existing methods to detect similar binding sites in unrelated proteins by 5-10%. All data reported in this paper are freely available at https://osf.io/6ngbs/ .}, } @article {pmid29523084, year = {2018}, author = {Liu, J and Xiao, Y and Wu, X and Jiang, L and Yang, S and Ding, Z and Fang, Z and Hua, H and Kirby, MS and Shou, J}, title = {A circulating microRNA signature as noninvasive diagnostic and prognostic biomarkers for nonalcoholic steatohepatitis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {188}, pmid = {29523084}, issn = {1471-2164}, mesh = {Animals ; Biomarkers/*blood ; Circulating MicroRNA/blood/*genetics ; Disease Progression ; *Gene Expression Profiling ; Humans ; Liver/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Non-alcoholic Fatty Liver Disease/blood/*diagnosis/genetics ; Prognosis ; }, abstract = {BACKGROUND: Noninvasive biomarkers are urgently needed for patients with nonalcoholic steatohepatitis (NASH) to assist in diagnosis, monitoring disease progression and assessing treatment response. Recently several exploratory studies showed that circulating level of microRNA is associated with NASH and correlated with disease severity. Although these data were encouraging, the application of circulating microRNA as biomarkers for patient screening and stratification need to be further assessed under well-controlled conditions.

RESULTS: The expression of circulating microRNAs were profiled in diet-induced NASH progression and regression models to assess the diagnostic and prognostic values and the translatability between preclinical mouse model and men. Since these mice had same genetic background and were housed in the same conditions, there were minimal confounding factors. Histopathological lesions were analyzed at distinct disease progression stages along with microRNA measurement which allows longitudinal assessment of microRNA as NASH biomarkers. Next, differentially expressed microRNAs were identified and validated in an independent cohorts of animals. Thirdly, these microRNAs were examined in a NASH regression model to assess whether they would respond to NASH treatment. MicroRNA profiling in two independent cohorts of animals validated the up-regulation of 6 microRNAs (miR-122, miR-192, miR-21, miR-29a, miR-34a and miR-505) in NASH mice, which was designated as the circulating microRNA signature for NASH. The microRNA signature could accurately distinguish NASH mice from lean mice, and it responded to chow diet treatment in a NASH regression model. To further improve the performance of microRNA-based biomarker, a new composite biomarker was proposed, which consists of miR-192, miR-21, miR-505 and ALT. The new composite biomarker outperformed the microRNA signature in predicting NASH mice which had NAS > 3, and deserves further validations in large scale studies.

CONCLUSION: The present study supported the translation of circulating microRNAs between preclinical models and humans in NASH pathogenesis and progression. The microRNA-based composite biomarker may be used for non-invasive diagnosis, clinical monitoring and assessing treatment response for NASH.}, } @article {pmid29523083, year = {2018}, author = {Zhang, H and Chan, Y and Fan, K and Schmidt, B and Liu, W}, title = {Fast and efficient short read mapping based on a succinct hash index.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {92}, pmid = {29523083}, issn = {1471-2105}, mesh = {*Algorithms ; Base Pairing/genetics ; Base Sequence ; Computer Simulation ; Databases, Genetic ; Genome, Human ; Humans ; Sequence Analysis, DNA/*methods ; Software ; }, abstract = {BACKGROUND: Various indexing techniques have been applied by next generation sequencing read mapping tools. The choice of a particular data structure is a trade-off between memory consumption, mapping throughput, and construction time.

RESULTS: We present the succinct hash index - a novel data structure for read mapping which is a variant of the classical q-gram index with a particularly small memory footprint occupying between 3.5 and 5.3 GB for a human reference genome for typical parameter settings. The succinct hash index features two novel seed selection algorithms (group seeding and variable-length seeding) and an efficient parallel construction algorithm, which we have implemented to design the FEM (Fast(F) and Efficient(E) read Mapper(M)) mapper. FEM can return all read mappings within a given edit distance. Our experimental results show that FEM is scalable and outperforms other state-of-the-art all-mappers in terms of both speed and memory footprint. Compared to Masai, FEM is an order-of-magnitude faster using a single thread and two orders-of-magnitude faster when using multiple threads. Furthermore, we observe an up to 2.8-fold speedup compared to BitMapper and an order-of-magnitude speedup compared to BitMapper2 and Hobbes3.

CONCLUSIONS: The presented succinct index is the first feasible implementation of the q-gram index functionality that occupies around 3.5 GB of memory for a whole human reference genome. FEM is freely available at https://github.com/haowenz/FEM .}, } @article {pmid29523080, year = {2018}, author = {Moore, GG and Mack, BM and Beltz, SB and Puel, O}, title = {Genome sequence of an aflatoxigenic pathogen of Argentinian peanut, Aspergillus arachidicola.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {189}, pmid = {29523080}, issn = {1471-2164}, mesh = {Aflatoxins/*metabolism ; Arachis/microbiology ; Aspergillus/*genetics/metabolism ; Fungal Proteins/genetics ; Gene Expression Profiling ; Gene Ontology ; *Genome, Fungal ; High-Throughput Nucleotide Sequencing/*methods ; Molecular Sequence Annotation ; Plant Diseases/microbiology ; *Transcriptome ; }, abstract = {BACKGROUND: Aspergillus arachidicola is an aflatoxigenic fungal species, first isolated from the leaves of a wild peanut species native to Argentina. It has since been reported in maize, Brazil nut and human sputum samples. This aflatoxigenic species is capable of secreting both B and G aflatoxins, similar to A. parasiticus and A. nomius. It has other characteristics that may result in its misidentification as one of several other section Flavi species. This study offers a preliminary analysis of the A. arachidicola genome.

RESULTS: In this study we sequenced the genome of the A. arachidicola type strain (CBS 117610) and found its genome size to be 38.9 Mb, and its number of predicted genes to be 12,091, which are values comparable to those in other sequenced Aspergilli. A comparison of 57 known Aspergillus secondary metabolite gene clusters, among closely-related aflatoxigenic species, revealed nearly half were predicted to exist in the type strain of A. arachidicola. Of its predicted genes, 691 were identified as unique to the species and 60% were assigned Gene Ontology terms using BLAST2GO. Phylogenomic inference shows CBS 117610 sharing a most recent common ancestor with A. parasiticus. Finally, BLAST query of A. flavus mating-type idiomorph sequences to this strain revealed the presence of a single mating-type (MAT1-1) idiomorph.

CONCLUSIONS: Based on A. arachidicola morphological, genetic and chemotype similarities with A. flavus and A. parasiticus, sequencing the genome of A. arachidicola will contribute to our understanding of the evolutionary relatedness among aflatoxigenic fungi.}, } @article {pmid29523079, year = {2018}, author = {Li, G and Jima, D and Wright, FA and Nobel, AB}, title = {HT-eQTL: integrative expression quantitative trait loci analysis in a large number of human tissues.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {95}, pmid = {29523079}, issn = {1471-2105}, support = {R01MH090936/MH/NIMH NIH HHS/United States ; P30 ES025128/ES/NIEHS NIH HHS/United States ; R01HG009125/NH/NIH HHS/United States ; R01 MH101819/MH/NIMH NIH HHS/United States ; R01 MH090936/MH/NIMH NIH HHS/United States ; R01MH101819/MH/NIMH NIH HHS/United States ; R01 HG009125/HG/NHGRI NIH HHS/United States ; R01 HG008980/HG/NHGRI NIH HHS/United States ; 1613072//Division of Mathematical Sciences/International ; P42ES005948/ES/NIEHS NIH HHS/United States ; R01HG008980/HG/NHGRI NIH HHS/United States ; P30ES025128/ES/NIEHS NIH HHS/United States ; P42 ES005948/ES/NIEHS NIH HHS/United States ; }, mesh = {Algorithms ; Bayes Theorem ; Computer Simulation ; *Gene Expression Regulation ; Genome-Wide Association Study ; Genotype ; Humans ; Organ Specificity/*genetics ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/*genetics ; ROC Curve ; }, abstract = {BACKGROUND: Expression quantitative trait loci (eQTL) analysis identifies genetic markers associated with the expression of a gene. Most existing eQTL analyses and methods investigate association in a single, readily available tissue, such as blood. Joint analysis of eQTL in multiple tissues has the potential to improve, and expand the scope of, single-tissue analyses. Large-scale collaborative efforts such as the Genotype-Tissue Expression (GTEx) program are currently generating high quality data in a large number of tissues. However, computational constraints limit genome-wide multi-tissue eQTL analysis.

RESULTS: We develop an integrative method under a hierarchical Bayesian framework for eQTL analysis in a large number of tissues. The model fitting procedure is highly scalable, and the computing time is a polynomial function of the number of tissues. Multi-tissue eQTLs are identified through a local false discovery rate approach, which rigorously controls the false discovery rate. Using simulation and GTEx real data studies, we show that the proposed method has superior performance to existing methods in terms of computing time and the power of eQTL discovery.

CONCLUSIONS: We provide a scalable method for eQTL analysis in a large number of tissues. The method enables the identification of eQTL with different configurations and facilitates the characterization of tissue specificity.}, } @article {pmid29523077, year = {2018}, author = {Zhang, JM and Fan, J and Fan, HC and Rosenfeld, D and Tse, DN}, title = {An interpretable framework for clustering single-cell RNA-Seq datasets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {93}, pmid = {29523077}, issn = {1471-2105}, support = {R01 HG008164/HG/NHGRI NIH HHS/United States ; R01HG008164/HG/NHGRI NIH HHS/United States ; }, mesh = {Algorithms ; Cluster Analysis ; *Databases, Genetic ; Humans ; Leukocytes, Mononuclear/metabolism ; Reference Standards ; Sequence Analysis, RNA/*methods ; Single-Cell Analysis/*methods ; Software ; }, abstract = {BACKGROUND: With the recent proliferation of single-cell RNA-Seq experiments, several methods have been developed for unsupervised analysis of the resulting datasets. These methods often rely on unintuitive hyperparameters and do not explicitly address the subjectivity associated with clustering.

RESULTS: In this work, we present DendroSplit, an interpretable framework for analyzing single-cell RNA-Seq datasets that addresses both the clustering interpretability and clustering subjectivity issues. DendroSplit offers a novel perspective on the single-cell RNA-Seq clustering problem motivated by the definition of "cell type", allowing us to cluster using feature selection to uncover multiple levels of biologically meaningful populations in the data. We analyze several landmark single-cell datasets, demonstrating both the method's efficacy and computational efficiency.

CONCLUSION: DendroSplit offers a clustering framework that is comparable to existing methods in terms of accuracy and speed but is novel in its emphasis on interpretabilty. We provide the full DendroSplit software package at https://github.com/jessemzhang/dendrosplit .}, } @article {pmid29523074, year = {2018}, author = {Mata, AR and Pacheco, CM and Cruz Pérez, JF and Sáenz, MM and Baca, BE}, title = {In silico comparative analysis of GGDEF and EAL domain signaling proteins from the Azospirillum genomes.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {20}, pmid = {29523074}, issn = {1471-2180}, abstract = {BACKGROUND: The cyclic-di-GMP (c-di-GMP) second messenger exemplifies a signaling system that regulates many bacterial behaviors of key importance; among them, c-di-GMP controls the transition between motile and sessile life-styles in bacteria. Cellular c-di-GMP levels in bacteria are regulated by the opposite enzymatic activities of diguanylate cyclases and phosphodiesterases, which are proteins that have GGDEF and EAL domains, respectively. Azospirillum is a genus of plant-growth-promoting bacteria, and members of this genus have beneficial effects in many agronomically and ecologically essential plants. These bacteria also inhabit aquatic ecosystems, and have been isolated from humus-reducing habitats. Bioinformatic and structural approaches were used to identify genes predicted to encode GG[D/E]EF, EAL and GG[D/E]EF-EAL domain proteins from nine genome sequences.

RESULTS: The analyzed sequences revealed that the genomes of A. humicireducens SgZ-5T, A. lipoferum 4B, Azospirillum sp. B510, A. thiophilum BV-ST, A. halopraeferens DSM3675, A. oryzae A2P, and A. brasilense Sp7, Sp245 and Az39 encode for 29 to 41 of these predicted proteins. Notably, only 15 proteins were conserved in all nine genomes: eight GGDEF, three EAL and four GGDEF-EAL hybrid domain proteins, all of which corresponded to core genes in the genomes. The predicted proteins exhibited variable lengths, architectures and sensor domains. In addition, the predicted cellular localizations showed that some of the proteins to contain transmembrane domains, suggesting that these proteins are anchored to the membrane. Therefore, as reported in other soil bacteria, the Azospirillum genomes encode a large number of proteins that are likely involved in c-di-GMP metabolism. In addition, the data obtained here strongly suggest host specificity and environment specific adaptation.

CONCLUSIONS: Bacteria of the Azospirillum genus cope with diverse environmental conditions to survive in soil and aquatic habitats and, in certain cases, to colonize and benefit their host plant. Gaining information on the structures of proteins involved in c-di-GMP metabolism in Azospirillum appears to be an important step in determining the c-di-GMP signaling pathways, involved in the transition of a motile cell towards a biofilm life-style, as an example of microbial genome plasticity under diverse in situ environments.}, } @article {pmid29523071, year = {2018}, author = {Dutta, S and Biswas, P and Chakraborty, S and Mitra, D and Pal, A and Das, M}, title = {Identification, characterization and gene expression analyses of important flowering genes related to photoperiodic pathway in bamboo.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {190}, pmid = {29523071}, issn = {1471-2164}, support = {38(1386)/14/EMR-II//Council of Scientific and Industrial Research/International ; BT/PR10778/PBD/16/1070/2014//Department of Biotechnology , Ministry of Science and Technology/International ; }, mesh = {Bambusa/*genetics/growth & development ; *Circadian Rhythm ; Flowers/*genetics/growth & development ; *Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Photoperiod ; Phylogeny ; }, abstract = {BACKGROUND: Bamboo is an important member of the family Poaceae and has many inflorescence and flowering features rarely observed in other plant groups. It retains an unusual form of perennialism by having a long vegetative phase that can extend up to 120 years, followed by flowering and death of the plants. In contrast to a large number of studies conducted on the annual, reference plants Arabidopsis thaliana and rice, molecular studies to characterize flowering pathways in perennial bamboo are lacking. Since photoperiod plays a crucial role in flower induction in most plants, important genes involved in this pathway have been studied in the field grown Bambusa tulda, which flowers after 40-50 years.

RESULTS: We identified several genes from B. tulda, including four related to the circadian clock [LATE ELONGATED HYPOCOTYL (LHY), TIMING OF CAB EXPRESSION1 (TOC1), ZEITLUPE (ZTL) and GIGANTEA (GI)], two circadian clock response integrators [CONSTANS A (COA), CONSTANS B (COB)] and four floral pathway integrators [FLOWERING LOCUS T1, 2, 3, 4 (FT1, 2, 3, 4)]. These genes were amplified from either gDNA and/or cDNA using degenerate as well as gene specific primers based on homologous sequences obtained from related monocot species. The sequence identity and phylogenetic comparisons revealed their close relationships to homologs identified in the temperate bamboo Phyllostachys edulis. While the four BtFT homologs were highly similar to each other, BtCOA possessed a full-length B-box domain that was truncated in BtCOB. Analysis of the spatial expression of these genes in selected flowering and non-flowering tissue stages indicated their possible involvement in flowering. The diurnal expression patterns of the clock genes were comparable to their homologs in rice, except for BtZTL. Among multiple BtCO and BtFT homologs, the diurnal pattern of only BtCOA and BtFT3, 4 were synchronized in the flower inductive tissue, but not in the non-flowering tissues.

CONCLUSION: This study elucidates the photoperiodic regulation of bamboo homologs of important flowering genes. The finding also identifies copy number expansion and gene expression divergence of CO and FT in bamboo. Further studies are required to understand their functional role in bamboo flowering.}, } @article {pmid29523070, year = {2018}, author = {Müller, HM and Van Auken, KM and Li, Y and Sternberg, PW}, title = {Textpresso Central: a customizable platform for searching, text mining, viewing, and curating biomedical literature.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {94}, pmid = {29523070}, issn = {1471-2105}, support = {U41 HG002223/HG/NHGRI NIH HHS/United States ; U41 HG002273/HG/NHGRI NIH HHS/United States ; U41-HG002223/HG/NHGRI NIH HHS/United States ; U41-HG002273/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Algorithms ; Animals ; Caenorhabditis elegans/*genetics ; Data Mining/*methods ; Gene Ontology ; Humans ; Internet ; Molecular Sequence Annotation ; *PubMed ; *Publications ; *Search Engine ; User-Computer Interface ; }, abstract = {BACKGROUND: The biomedical literature continues to grow at a rapid pace, making the challenge of knowledge retrieval and extraction ever greater. Tools that provide a means to search and mine the full text of literature thus represent an important way by which the efficiency of these processes can be improved.

RESULTS: We describe the next generation of the Textpresso information retrieval system, Textpresso Central (TPC). TPC builds on the strengths of the original system by expanding the full text corpus to include the PubMed Central Open Access Subset (PMC OA), as well as the WormBase C. elegans bibliography. In addition, TPC allows users to create a customized corpus by uploading and processing documents of their choosing. TPC is UIMA compliant, to facilitate compatibility with external processing modules, and takes advantage of Lucene indexing and search technology for efficient handling of millions of full text documents. Like Textpresso, TPC searches can be performed using keywords and/or categories (semantically related groups of terms), but to provide better context for interpreting and validating queries, search results may now be viewed as highlighted passages in the context of full text. To facilitate biocuration efforts, TPC also allows users to select text spans from the full text and annotate them, create customized curation forms for any data type, and send resulting annotations to external curation databases. As an example of such a curation form, we describe integration of TPC with the Noctua curation tool developed by the Gene Ontology (GO) Consortium.

CONCLUSION: Textpresso Central is an online literature search and curation platform that enables biocurators and biomedical researchers to search and mine the full text of literature by integrating keyword and category searches with viewing search results in the context of the full text. It also allows users to create customized curation interfaces, use those interfaces to make annotations linked to supporting evidence statements, and then send those annotations to any database in the world. Textpresso Central URL: http://www.textpresso.org/tpc.}, } @article {pmid29522814, year = {2018}, author = {Schweizer, M and Liu, Y and Olsson, U and Shirihai, H and Huang, Q and Leader, PJ and Copete, JL and Kirwan, GM and Chen, G and Svensson, L}, title = {Contrasting patterns of diversification in two sister species of martins (Aves: Hirundinidae): The Sand Martin Riparia riparia and the Pale Martin R. diluta.}, journal = {Molecular phylogenetics and evolution}, volume = {125}, number = {}, pages = {116-126}, doi = {10.1016/j.ympev.2018.02.026}, pmid = {29522814}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Breeding ; Calibration ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Genetic Markers ; *Genetic Variation ; Geography ; Haplotypes/genetics ; Phylogeny ; Phylogeography ; Principal Component Analysis ; Species Specificity ; Swallows/anatomy & histology/*genetics ; }, abstract = {Species not only responded idiosyncratically to past climate changes, there were also regionally contrasting effects on spatio-temporal diversification patterns. Studies of closely related species appear to be a particularly promising comparative approach to disentangle such regionally differential impacts. In this study, we undertook a comprehensive geographic sampling to investigate the evolutionary history of the Holarctic Sand Martin Riparia riparia and the chiefly Central and East Asian Pale Martin R. diluta. Previous phylogenetic studies using only a limited geographic sampling, particularly for the latter, revealed the two to be genetically distinct, with the former showing only a shallow genetic structure in mitochondrial DNA. Based on one mitochondrial, one autosomal and one Z-linked nuclear marker, we confirmed the shallow genetic structure in R. riparia even when including the morphologically relatively distinct subspecies R. r. shelleyi from the Nile Valley in Egypt and probably the Middle East. On the other hand the different subspecies of R. diluta, i.e. R. d. diluta from Central Asia, R. d. indica from the northwestern Indian Subcontinent, R. d. tibetana from the Tibetan Plateau and R. d. fohkienensis from southeastern China, were found to be genetically distinct. Their diversification started before the Early to Middle Pleistocene Transition, which was followed by a pronounced succession of glacial and interglacial periods. These rather old divergence events contrast with the lack of any strong phylogeographic structure in R. riparia. Strongly structured populations and regional diversification have been reported in different forest passerine families of South-East Asia. Here we demonstrate, however, that species characteristic of open-country habitats such as R. diluta might display a similar pattern. Morphometric analyses of 120 individuals revealed no clear differences between the different subspecies of R. diluta. Given their similarity also in plumage features, we refrain from proposing any splits despite their marked genetic differentiation, pending further studies and particularly the discovery of potential secondary contact zones.}, } @article {pmid29522707, year = {2018}, author = {Alkobtawi, M and Ray, H and Barriga, EH and Moreno, M and Kerney, R and Monsoro-Burq, AH and Saint-Jeannet, JP and Mayor, R}, title = {Characterization of Pax3 and Sox10 transgenic Xenopus laevis embryos as tools to study neural crest development.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.02.020}, pmid = {29522707}, issn = {1095-564X}, support = {K12 GM088010/GM/NIGMS NIH HHS/United States ; }, abstract = {The neural crest is a multipotent population of cells that originates a variety of cell types. Many animal models are used to study neural crest induction, migration and differentiation, with amphibians and birds being the most widely used systems. A major technological advance to study neural crest development in mouse, chick and zebrafish has been the generation of transgenic animals in which neural crest specific enhancers/promoters drive the expression of either fluorescent proteins for use as lineage tracers, or modified genes for use in functional studies. Unfortunately, no such transgenic animals currently exist for the amphibians Xenopus laevis and tropicalis, key model systems for studying neural crest development. Here we describe the generation and characterization of two transgenic Xenopus laevis lines, Pax3-GFP and Sox10-GFP, in which GFP is expressed in the pre-migratory and migratory neural crest, respectively. We show that Pax3-GFP could be a powerful tool to study neural crest induction, whereas Sox10-GFP could be used in the study of neural crest migration in living embryos.}, } @article {pmid29522254, year = {2018}, author = {Wagner, MR and Mitchell-Olds, T}, title = {Plasticity of plant defense and its evolutionary implications in wild populations of Boechera stricta.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1034-1049}, pmid = {29522254}, issn = {1558-5646}, support = {R01 GM086496/GM/NIGMS NIH HHS/United States ; S10 OD018164/OD/NIH HHS/United States ; }, abstract = {Phenotypic plasticity is thought to impact evolutionary trajectories by shifting trait values in a direction that is either favored by natural selection ("adaptive" plasticity) or disfavored ("nonadaptive" plasticity). However, it is unclear how commonly each of these types of plasticity occurs in natural populations. To answer this question, we measured glucosinolate defensive chemistry and reproductive fitness in over 1500 individuals of the wild perennial mustard Boechera stricta, planted in four common gardens across central Idaho, United States. Glucosinolate profiles-including total glucosinolate concentration as well as the relative abundances and overall diversity of different compounds-were strongly plastic both among habitats and within habitats. Patterns of glucosinolate plasticity varied greatly among genotypes. Plasticity among sites was predicted to affect fitness in 27.1% of cases; more often than expected by chance, glucosinolate plasticity increased rather than decreased relative fitness. In contrast, we found no evidence for within-habitat selection on glucosinolate reaction norm slopes (i.e., plasticity along a continuous environmental gradient). Together, our results indicate that glucosinolate plasticity may improve the ability of B. stricta populations to persist after migration to new habitats.}, } @article {pmid29522209, year = {2018}, author = {Schippers, KJ and Nichols, SA}, title = {Evidence of Signaling and Adhesion Roles for β-Catenin in the Sponge Ephydatia muelleri.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1407-1421}, doi = {10.1093/molbev/msy033}, pmid = {29522209}, issn = {1537-1719}, abstract = {β-Catenin acts as a transcriptional coactivator in the Wnt/β-catenin signaling pathway and a cytoplasmic effector in cadherin-based cell adhesion. These functions are ancient within animals, but the earliest steps in β-catenin evolution remain unresolved due to limited data from key lineages-sponges, ctenophores, and placozoans. Previous studies in sponges have characterized β-catenin expression dynamics and used GSK3B antagonists to ectopically activate the Wnt/β-catenin pathway; both approaches rely upon untested assumptions about the conservation of β-catenin function and regulation in sponges. Here, we test these assumptions using an antibody raised against β-catenin from the sponge Ephydatia muelleri. We find that cadherin-complex genes coprecipitate with endogenous Em β-catenin from cell lysates, but that Wnt pathway components do not. However, through immunostaining we detect both cell boundary and nuclear populations, and we find evidence that Em β-catenin is a conserved substrate of GSK3B. Collectively, these data support conserved roles for Em β-catenin in both cell adhesion and Wnt signaling. Additionally, we find evidence for an Em β-catenin population associated with the distal ends of F-actin stress fibers in apparent cell-substrate adhesion structures that resemble focal adhesions. This finding suggests a fundamental difference in the adhesion properties of sponge tissues relative to other animals, in which the adhesion functions of β-catenin are typically restricted to cell-cell adhesions.}, } @article {pmid29522102, year = {2018}, author = {Beleva Guthrie, V and Masica, DL and Fraser, A and Federico, J and Fan, Y and Camps, M and Karchin, R}, title = {Network Analysis of Protein Adaptation: Modeling the Functional Impact of Multiple Mutations.}, journal = {Molecular biology and evolution}, volume = {35}, number = {6}, pages = {1507-1519}, pmid = {29522102}, issn = {1537-1719}, support = {T32 GM007309/GM/NIGMS NIH HHS/United States ; }, abstract = {The evolution of new biochemical activities frequently involves complex dependencies between mutations and rapid evolutionary radiation. Mutation co-occurrence and covariation have previously been used to identify compensating mutations that are the result of physical contacts and preserve protein function and fold. Here, we model pairwise functional dependencies and higher order interactions that enable evolution of new protein functions. We use a network model to find complex dependencies between mutations resulting from evolutionary trade-offs and pleiotropic effects. We present a method to construct these networks and to identify functionally interacting mutations in both extant and reconstructed ancestral sequences (Network Analysis of Protein Adaptation). The time ordering of mutations can be incorporated into the networks through phylogenetic reconstruction. We apply NAPA to three distantly homologous β-lactamase protein clusters (TEM, CTX-M-3, and OXA-51), each of which has experienced recent evolutionary radiation under substantially different selective pressures. By analyzing the network properties of each protein cluster, we identify key adaptive mutations, positive pairwise interactions, different adaptive solutions to the same selective pressure, and complex evolutionary trajectories likely to increase protein fitness. We also present evidence that incorporating information from phylogenetic reconstruction and ancestral sequence inference can reduce the number of spurious links in the network, whereas preserving overall network community structure. The analysis does not require structural or biochemical data. In contrast to function-preserving mutation dependencies, which are frequently from structural contacts, gain-of-function mutation dependencies are most commonly between residues distal in protein structure.}, } @article {pmid29521615, year = {2018}, author = {Shin, SK and Kim, E and Yi, H}, title = {Tenacibaculum todarodis sp. nov., isolated from a squid.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1479-1483}, doi = {10.1099/ijsem.0.002692}, pmid = {29521615}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Decapodiformes/*microbiology ; Fatty Acids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Tenacibaculum/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, aerobic bacterial strain, designated LPB0136T, was isolated from a squid Todarodes pacificus, caught in the East Sea, off Korea. LPB0136T contained a circular chromosome of 3.02 Mb with a DNA G+C content of 30.7 mol%. The genome included 2726 protein-coding genes and three copies of rRNA operons. Phylogenetic analysis of the 16S rRNA gene sequence indicated that this isolate represents a member of the genus Tenacibaculum with an independent genomic species status, showing sequence similarities of 95.9 % to Tenacibaculum aestuarii SMK-4T and Tenacibaculum caenipelagi HJ-26MT. The detected respiratory quinone (MK-6) and major polar lipid (phosphatidylethanolamine) were similar to the chemotaxonomic profile of other species of the genus Tenacibaculum. The major cellular fatty acids profile (iso-C15 : 0, iso-C15 : 0 3-OH and iso-C15 : 0G) was also similar to those of members of genus Tenacibaculum, but the contents and amounts differed from those of closely related neighbours. Many biochemical and physiological characteristics also distinguished the isolate from other species within the genus Tenacibaculum. On the basis of the pholyphasic taxonomic data determined in this study, strain LPB0136T represents a novel species of the genus Tenacibaculum, for which the name Tenacibaculum todarodis sp. nov. is proposed. The type strain is LPB0136T (=KACC 18887T=JCM 31564T).}, } @article {pmid29521614, year = {2018}, author = {Thanh, VN and Duc Hien, D and Yaguchi, T and Sampaio, JP and Lachance, MA}, title = {Moniliella sojae sp. nov., a species of black yeasts isolated from Vietnamese soy paste (tuong), and reassignment of Moniliella suaveolens strains to Moniliella pyrgileucina sp. nov., Moniliella casei sp. nov. and Moniliella macrospora emend. comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1806-1814}, doi = {10.1099/ijsem.0.002690}, pmid = {29521614}, issn = {1466-5034}, mesh = {Ascomycota/*classification/genetics/isolation & purification ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; *Food Microbiology ; Mycological Typing Techniques ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Soybeans/*microbiology ; Vietnam ; }, abstract = {The presence of yeasts at different steps of Vietnamese soy paste production was studied. Yeast growth occurred during primary soybean fermentation, with the cell density reaching 4.106 c.f.u. ml-1, and terminated during brine fermentation. The dominant species were Pichia kudriavzevii and Millerozyma farinosa. Over the span of 14 years, nine strains of Moniliella were isolated. The strains had identical PCR fingerprints generated with primer (GAC)5 and identical D1/D2 and internal transcribed spacer (ITS) sequences. A D1/D2-based phylogeny indicated that the strains were closest to a group of four previously assigned as Moniliella suaveolens strains. Together they form a new lineage that is well separated from all known species, including M. suaveolens (over 12.7 % divergence). ITS sequences indicated the presence of four species differing from each other by 9-57 nt. The name Moniliella sojae sp. nov. is proposed to accommodate the strains isolated from Vietnamese soy paste, Moniliella pyrgileucina sp. nov. is proposed for PYCC 6800 and Moniliella casei sp. nov. is proposed for CBS 157.58. An emended combination Moniliella macrospora is proposed for CBS 221.32 and CBS 223.32. The type strains and MycoBank numbers are: M. sojae sp. nov., SS 4.2T=CBS 126448T=NRRL Y-48680T and MB 822871; M. pyrgileucina sp. nov., PYCC 6800T=CBS 15203T and MB 823030; M. casei sp. nov., CBS 157.58T=IFM 60348T and MB 822872; M. macrospora emend. comb. nov., CBS 221.32T (=MUCL 11527T) and MB 822874.}, } @article {pmid29521613, year = {2018}, author = {Park, S and Choi, J and Choi, SJ and Yoon, JH}, title = {Pseudobizionia ponticola gen. nov., sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1467-1473}, doi = {10.1099/ijsem.0.002691}, pmid = {29521613}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated MM-14T, was isolated from seawater sampled from the Yellow Sea in the Republic of Korea and its taxonomic position was investigated using a polyphasic approach. Strain MM-14T grew optimally at 30 °C and in the presence of approximately 2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain MM-14T clustered with the type strain of Hanstruepera neustonica. The novel strain exhibited a 16S rRNA gene sequence similarity value of 96.06 % to the type strain of H. neustonica, but higher 16S rRNA gene sequence similarity values (96.13-96.69 %) to the type strains of Bizionia echini, Bizionia hallyeonensis and Bizionia psychrotolerans. Strain MM-14T contained MK-6 as the predominant menaquinone and iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH as the major fatty acids. The major polar lipids were phosphatidylethanolamine, one unidentified lipid and one unidentified aminolipid. The DNA G+C content of strain MM-14T was 34.6 mol%. The phylogenetic and chemotaxonomic data and other phenotypic properties revealed that strain MM-14T constitutes a new genus and species within the family Flavobacteriaceae of the phylum Bacteroidetes, for which the name Pseudobizionia ponticola gen. nov., sp. nov. is proposed. The type strain of Pseudobizionia ponticola is MM-14T (=KACC 19434T=KCTC 62139T=NBRC 113019T).}, } @article {pmid29521480, year = {2018}, author = {Gonçalves, CF and Pacheco, CC and Tamagnini, P and Oliveira, P}, title = {Identification of inner membrane translocase components of TolC-mediated secretion in the cyanobacterium Synechocystis sp. PCC 6803.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2354-2369}, doi = {10.1111/1462-2920.14095}, pmid = {29521480}, issn = {1462-2920}, abstract = {Cyanobacteria were the first organisms ever to perform oxygenic photosynthesis and still significantly contribute to primary production on a global scale. To assure the proper functioning of their primary metabolism and cell homeostasis, cyanobacteria must rely on efficient transport systems to cross their multilayered cell envelope. However, cyanobacterial secretion mechanisms remain largely unknown. Here, we report on the identification of 11 putative inner membrane translocase components of TolC-mediated secretion in the unicellular cyanobacterium Synechocystis sp. PCC 6803. Gene-inactivation of each of the candidate genes followed by a comprehensive phenotypic characterization allowed to link specific protein components to the processes of protein export (as part of the type I secretion system) and drug efflux (part of the resistance-division-nodulation efflux pumps). In addition, mutants in genes sll0141, sll0180 and slr0369 exhibited alterations in pilin glycosylation, but pili structures could still be observed by transmission electron microscopy. By studying the release of outer membrane vesicles (OMVs), an alternative secretion route, on mutants with impaired secretory functions we suggest that the hyper-vesiculating phenotype of the TolC-deficient mutant is related to cell envelope stress management. Altogether, these findings highlight how both classical (TolC-mediated) and nonclassical (OMVs-mediated) secretion systems are crucial for cyanobacterial cell homeostasis.}, } @article {pmid29521473, year = {2018}, author = {Straub, C and Colombi, E and Li, L and Huang, H and Templeton, MD and McCann, HC and Rainey, PB}, title = {The ecological genetics of Pseudomonas syringae from kiwifruit leaves.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14092}, pmid = {29521473}, issn = {1462-2920}, abstract = {Interactions between commensal microbes and invading pathogens are understudied, despite their likely effects on pathogen population structure and infection processes. We describe the population structure and genetic diversity of a broad range of co-occurring Pseudomonas syringae isolated from infected and uninfected kiwifruit during an outbreak of bleeding canker disease caused by P. syringae pv. actinidiae (Psa) in New Zealand. Overall population structure was clonal and affected by ecological factors including infection status and cultivar. Most isolates are members of a new clade in phylogroup 3 (PG3a), also present on kiwifruit leaves in China and Japan. Stability of the polymorphism between pathogenic Psa and commensal P. syringae PG3a isolated from the same leaf was tested using reciprocal invasion from rare assays in vitro and in planta. P. syringae G33C (PG3a) inhibited Psa NZ54, while the presence of Psa NZ54 enhanced the growth of P. syringae G33C. This effect could not be attributed to virulence activity encoded by the Type 3 secretion system of Psa. Together our data contribute toward the development of an ecological perspective on the genetic structure of pathogen populations.}, } @article {pmid29521469, year = {2018}, author = {Miao, J and Li, X and Lin, D and Liu, X and Tyler, BM}, title = {Oxysterol-binding protein-related protein 2 is not essential for Phytophthora sojae based on CRISPR/Cas9 deletions.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {293-298}, doi = {10.1111/1758-2229.12638}, pmid = {29521469}, issn = {1758-2229}, abstract = {Oxysterol-binding protein (OSBP)-related proteins (ORPs) are a large conserved family of lipid transfer proteins in eukaryotes. In oomycetes, some ORPs are the target of the novel oomycide oxathiapiprolin. By searching the Phytophthora sojae genome database, two ORP proteins, PsORP1 (Protein ID: 558498) and PsORP2 (Protein ID: 470921), were found. Here, we investigated the biological function of PsORP2. The expression level of PsORP2 was higher in germinated cysts and late infection than in other developmental stages. However, deletion of PsORP2 using CRISPR/Cas9 had no significant effect on sporangia production, zoospore production, cyst germination, oospore production, virulence or oxathiapiprolin sensitivity. PsORP1 also was not upregulated in ΔPsORP2 transformants. Collectively, our studies demonstrate that PsORP2 is not an essential protein for development or virulence in P. sojae under the conditions we tested.}, } @article {pmid29521452, year = {2018}, author = {Scott, KM and Williams, J and Porter, CMB and Russel, S and Harmer, TL and Paul, JH and Antonen, KM and Bridges, MK and Camper, GJ and Campla, CK and Casella, LG and Chase, E and Conrad, JW and Cruz, MC and Dunlap, DS and Duran, L and Fahsbender, EM and Goldsmith, DB and Keeley, RF and Kondoff, MR and Kussy, BI and Lane, MK and Lawler, S and Leigh, BA and Lewis, C and Lostal, LM and Marking, D and Mancera, PA and McClenthan, EC and McIntyre, EA and Mine, JA and Modi, S and Moore, BD and Morgan, WA and Nelson, KM and Nguyen, KN and Ogburn, N and Parrino, DG and Pedapudi, AD and Pelham, RP and Preece, AM and Rampersad, EA and Richardson, JC and Rodgers, CM and Schaffer, BL and Sheridan, NE and Solone, MR and Staley, ZR and Tabuchi, M and Waide, RJ and Wanjugi, PW and Young, S and Clum, A and Daum, C and Huntemann, M and Ivanova, N and Kyrpides, N and Mikhailova, N and Palaniappan, K and Pillay, M and Reddy, TBK and Shapiro, N and Stamatis, D and Varghese, N and Woyke, T and Boden, R and Freyermuth, SK and Kerfeld, CA}, title = {Genomes of ubiquitous marine and hypersaline Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira spp. encode a diversity of mechanisms to sustain chemolithoautotrophy in heterogeneous environments.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2686-2708}, doi = {10.1111/1462-2920.14090}, pmid = {29521452}, issn = {1462-2920}, support = {MOE-2008-02036//USDA Higher Education Challenge Grant/ ; NSF-IOS-1257532//USDA Higher Education Challenge Grant/ ; DE-AC02-05CH11231//Office of Science of the U.S. Department of Energy/ ; }, abstract = {Chemolithoautotrophic bacteria from the genera Hydrogenovibrio, Thiomicrorhabdus and Thiomicrospira are common, sometimes dominant, isolates from sulfidic habitats including hydrothermal vents, soda and salt lakes and marine sediments. Their genome sequences confirm their membership in a deeply branching clade of the Gammaproteobacteria. Several adaptations to heterogeneous habitats are apparent. Their genomes include large numbers of genes for sensing and responding to their environment (EAL- and GGDEF-domain proteins and methyl-accepting chemotaxis proteins) despite their small sizes (2.1-3.1 Mbp). An array of sulfur-oxidizing complexes are encoded, likely to facilitate these organisms' use of multiple forms of reduced sulfur as electron donors. Hydrogenase genes are present in some taxa, including group 1d and 2b hydrogenases in Hydrogenovibrio marinus and H. thermophilus MA2-6, acquired via horizontal gene transfer. In addition to high-affinity cbb3 cytochrome c oxidase, some also encode cytochrome bd-type quinol oxidase or ba3 -type cytochrome c oxidase, which could facilitate growth under different oxygen tensions, or maintain redox balance. Carboxysome operons are present in most, with genes downstream encoding transporters from four evolutionarily distinct families, which may act with the carboxysomes to form CO2 concentrating mechanisms. These adaptations to habitat variability likely contribute to the cosmopolitan distribution of these organisms.}, } @article {pmid29521443, year = {2018}, author = {Ankrah, NYD and Douglas, AE}, title = {Nutrient factories: metabolic function of beneficial microorganisms associated with insects.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14097}, pmid = {29521443}, issn = {1462-2920}, abstract = {Many symbiotic microorganisms in animals, including insects, have parallels to microbial nutrient factories of biotechnology: just as the metabolism of individual microorganisms and microbial communities is modified by biotechnologists to produce specific nutrients, so the many insect-associated microorganisms synthesize specific nutrients that support the sustained growth and reproduction of their animal host. Three broad metabolic functions are mediated by insect-associated microorganisms: (i) fermentation of dietary constituents, releasing products that contribute to host carbon and energy metabolism; (ii) overproduction of nutrients, notably essential amino acids, required by the host and (iii) recycling of host waste metabolites. In many systems, the nutrients that are released from living microbial cells have been identified, with evidence for metabolite cross-feeding and shared metabolic pathways both among different microbial taxa and between microorganisms and the host. However, the flux of nutrients from microbial cells to host has rarely been quantified; our understanding of the processes that regulate nutrient transfer is fragmentary; and the scale and mechanism of metabolic adaptations of microorganisms to host nutritional demand are largely unknown. Recent advances in metabolic, microscopical and modelling techniques offer excellent opportunities to resolve these outstanding issues, with insights that can contribute to the effective design of nutrient factories for biotechnological applications.}, } @article {pmid29521441, year = {2018}, author = {Purves, J and Thomas, J and Riboldi, GP and Zapotoczna, M and Tarrant, E and Andrew, PW and Londoño, A and Planet, PJ and Geoghegan, JA and Waldron, KJ and Morrissey, JA}, title = {A horizontally gene transferred copper resistance locus confers hyper-resistance to antibacterial copper toxicity and enables survival of community acquired methicillin resistant Staphylococcus aureus USA300 in macrophages.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1576-1589}, pmid = {29521441}, issn = {1462-2920}, support = {//Wellcome Trust/United Kingdom ; HHSN272200700055C/AI/NIAID NIH HHS/United States ; }, abstract = {Excess copper is highly toxic and forms part of the host innate immune system's antibacterial arsenal, accumulating at sites of infection and acting within macrophages to kill engulfed pathogens. We show for the first time that a novel, horizontally gene transferred copper resistance locus (copXL), uniquely associated with the SCCmec elements of the highly virulent, epidemic, community acquired methicillin resistant Staphylococcus aureus (CA-MRSA) USA300, confers copper hyper-resistance. These genes are additional to existing core genome copper resistance mechanisms, and are not found in typical S. aureus lineages, but are increasingly identified in emerging pathogenic isolates. Our data show that CopX, a putative P1B-3 -ATPase efflux transporter, and CopL, a novel lipoprotein, confer copper hyper-resistance compared to typical S. aureus strains. The copXL genes form an operon that is tightly repressed in low copper environments by the copper regulator CsoR. Significantly, CopX and CopL are important for S. aureus USA300 intracellular survival within macrophages. Therefore, the emergence of new S. aureus clones with the copXL locus has significant implications for public health because these genes confer increased resistance to antibacterial copper toxicity, enhancing bacterial fitness by altering S. aureus interaction with innate immunity.}, } @article {pmid29521439, year = {2018}, author = {Wear, EK and Wilbanks, EG and Nelson, CE and Carlson, CA}, title = {Primer selection impacts specific population abundances but not community dynamics in a monthly time-series 16S rRNA gene amplicon analysis of coastal marine bacterioplankton.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2709-2726}, pmid = {29521439}, issn = {1462-2920}, support = {NNX14AR62A//National Aeronautics and Space Administration Biodiversity and Ecological Forecasting program/ ; NNX12AO13H//National Aeronautics and Space Administration Biodiversity and Ecological Forecasting program/ ; MC15AC00006//Bureau of Ocean and Energy Management Ecosystem Studies program/ ; N/A//National Oceanic and Atmospheric Administration/ ; //Santa Barbara Channel Marine Biodiversity Observation Network/ ; //NASA Earth and Space Science Fellowship Program/ ; OCE-0850857//National Science Foundation Award/ ; //NASA Postdoctoral Fellowship/ ; OCE-1232779//NSF/ ; 1S10OD010786-01//NIH Shared Instrumentation/ ; //Division of Ocean Sciences/ ; //Bureau of Ocean and Energy Management/ ; }, abstract = {Primers targeting the 16S small subunit ribosomal RNA marker gene, used to characterize bacterial and archaeal communities, have recently been re-evaluated for marine planktonic habitats. To investigate whether primer selection affects the ecological interpretation of bacterioplankton populations and community dynamics, amplicon sequencing with four primer sets targeting several hypervariable regions of the 16S rRNA gene was conducted on both mock communities constructed from cloned 16S rRNA genes and a time-series of DNA samples from the temperate coastal Santa Barbara Channel. Ecological interpretations of community structure (delineation of depth and seasonality, correlations with environmental factors) were similar across primer sets, while population dynamics varied. We observed substantial differences in relative abundances of taxa known to be poorly resolved by some primer sets, such as Thaumarchaeota and SAR11, and unexpected taxa including Roseobacter clades. Though the magnitude of relative abundances of common OTUs differed between primer sets, the relative abundances of the OTUs were nonetheless strongly correlated. We do not endorse one primer set but rather enumerate strengths and weaknesses to facilitate selection appropriate to a system or experimental goal. While 16S rRNA gene primer bias suggests caution in assessing quantitative population dynamics, community dynamics appear robust across studies using different primers.}, } @article {pmid29520921, year = {2018}, author = {Sharbrough, J and Luse, M and Boore, JL and Logsdon, JM and Neiman, M}, title = {Radical amino acid mutations persist longer in the absence of sex.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {808-824}, doi = {10.1111/evo.13465}, pmid = {29520921}, issn = {1558-5646}, abstract = {Harmful mutations are ubiquitous and inevitable, and the rate at which these mutations are removed from populations is a critical determinant of evolutionary fate. Closely related sexual and asexual taxa provide a particularly powerful setting to study deleterious mutation elimination because sexual reproduction should facilitate mutational clearance by reducing selective interference between sites and by allowing the production of offspring with different mutational complements than their parents. Here, we compared the rate of removal of conservative (i.e., similar biochemical properties) and radical (i.e., distinct biochemical properties) nonsynonymous mutations from mitochondrial genomes of sexual versus asexual Potamopyrgus antipodarum, a New Zealand freshwater snail characterized by coexisting and ecologically similar sexual and asexual lineages. Our analyses revealed that radical nonsynonymous mutations are cleared at higher rates than conservative changes and that sexual lineages eliminate radical changes more rapidly than asexual counterparts. These results are consistent with reduced efficacy of purifying selection in asexual lineages allowing harmful mutations to remain polymorphic longer than in sexual lineages. Together, these data illuminate some of the population-level processes contributing to mitochondrial mutation accumulation and suggest that mutation accumulation could influence the outcome of competition between sexual and asexual lineages.}, } @article {pmid29520758, year = {2018}, author = {Hartfield, M}, title = {Digest: Effects of spatially-spreading adaptive mutations on genome-wide diversity.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {1015-1016}, doi = {10.1111/evo.13462}, pmid = {29520758}, issn = {1558-5646}, } @article {pmid29520513, year = {2018}, author = {Wu, Q and Zhang, G and Wang, B and Li, X and Yue, S and Chen, J and Zhang, H and Wang, H}, title = {Production and Identification of Inthomycin B Produced by a Deep-Sea Sediment-Derived Streptomyces sp. YB104 Based on Cultivation-Dependent Approach.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {942-951}, pmid = {29520513}, issn = {1432-0991}, support = {81773628//National Natural Science Foundation of China/ ; 41776139//National Natural Science Foundation of China/ ; 81741165//National Natural Science Foundation of China/ ; LY16H300008//Natural Science Foundation of Zhejiang Province/ ; LY16H300007//Natural Science Foundation of Zhejiang Province/ ; 2017YFE0103100//National Key Research and Development Program/ ; 2017M620254//China Postdoctoral Science Foundation/ ; }, mesh = {Biological Products/*metabolism ; Culture Media/chemistry/metabolism ; Fatty Acids, Unsaturated/*metabolism ; Geologic Sediments/*microbiology ; Oxazoles/*metabolism ; Streptomyces/genetics/growth & development/*isolation & purification/*metabolism ; }, abstract = {The natural products discovery program in our group utilizes deep-sea sediment-derived microorganisms and employs a bio-active guided isolation procedure and one strain many compounds (OSMAC) approach to screen bio-active natural products for practical applications in the medicinal and agricultural industry. OSMAC strategy is employed to stimulate secondary metabolite production through changing culture conditions. In this paper, we applied cultivation-dependent procedure, changing media type, leading to the discovery of a bio-active compound named inthomycin B (1) from a marine-derived Streptomyces sp. YB104. The compound was characterized based on extensive spectroscopic analyses and comparison to that in the reported literature. The quantification of inthomycin B demonstrated that Streptomyces sp. YB104 produced moderate yield of inthomycin B with a yield around 25 mg/l after 14 days. Thus, Streptomyces sp. YB104 was considered to be a useful potential as a first industrial-producing strain of inthomycins.}, } @article {pmid29520512, year = {2018}, author = {Ventura, C and Briones-Roblero, CI and Hernández, E and Rivera-Orduña, FN and Zúñiga, G}, title = {Comparative Analysis of the Gut Bacterial Community of Four Anastrepha Fruit Flies (Diptera: Tephritidae) Based on Pyrosequencing.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {966-976}, pmid = {29520512}, issn = {1432-0991}, support = {SIP 20141308//Instituto Politécnico Nacional Programa Institucional de Formación de Investigadores/ ; }, mesh = {Actinobacteria/classification/genetics/*isolation & purification ; Animals ; Bacterial Typing Techniques ; Base Sequence ; DNA, Bacterial/genetics ; Deinococcus/classification/genetics/*isolation & purification ; Firmicutes/classification/genetics/*isolation & purification ; *Gastrointestinal Microbiome ; Larva/microbiology ; Proteobacteria/classification/genetics/*isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Stomach/*microbiology ; Symbiosis ; Tephritidae/classification/*microbiology ; }, abstract = {Fruit flies are the most economically important group of phytophagous flies worldwide. Whereas the ecological role of bacteria associated with tephritid fruit fly species of the genera Bactrocera and Ceratitis has been demonstrated, the diversity of the bacterial community in Anastrepha has been poorly characterized. This study represents the first comprehensive analysis of the bacterial community in the gut of larvae and adults of Anastrepha ludens, A. obliqua, A. serpentina, and A. striata using 454 pyrosequencing. A total of four phyla, seven classes, 11 families, and 27 bacterial genera were identified. Proteobacteria was the most represented phylum, followed by Firmicutes, Actinobacteria, and Deinococcus-Thermus. The genera Citrobacter, Enterobacter, Escherichia, Klebsiella, and Raoultella were dominant in all samples analyzed. In general, the bacterial community diversity in adult flies was higher in species with a broader diet breadth than species with a restricted number of hosts, whereas it was also higher in adults versus larvae. Differences in bacterial communities in adults might be determined by the number of fruit species infested. Lastly, the predictive functional profile analysis suggested that community members may participate in metabolic pathways related to membrane transport and metabolism of carbohydrates, amino acids, cofactors, and lipids. These results provide the basis for the study of unexplored functional roles of bacteria in this insect group.}, } @article {pmid29519919, year = {2018}, author = {Tylewicz, S and Petterle, A and Marttila, S and Miskolczi, P and Azeez, A and Singh, RK and Immanen, J and Mähler, N and Hvidsten, TR and Eklund, DM and Bowman, JL and Helariutta, Y and Bhalerao, RP}, title = {Photoperiodic control of seasonal growth is mediated by ABA acting on cell-cell communication.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {212-215}, doi = {10.1126/science.aan8576}, pmid = {29519919}, issn = {1095-9203}, mesh = {Abscisic Acid/*physiology ; Cell Communication/*physiology ; Circadian Rhythm ; Meristem/cytology/growth & development ; *Photoperiod ; Plant Dormancy/*physiology ; Plant Growth Regulators/*physiology ; Populus/cytology/genetics/*growth & development ; Seasons ; Trees/cytology/genetics/*growth & development ; }, abstract = {In temperate and boreal ecosystems, seasonal cycles of growth and dormancy allow perennial plants to adapt to winter conditions. We show, in hybrid aspen trees, that photoperiodic regulation of dormancy is mechanistically distinct from autumnal growth cessation. Dormancy sets in when symplastic intercellular communication through plasmodesmata is blocked by a process dependent on the phytohormone abscisic acid. The communication blockage prevents growth-promoting signals from accessing the meristem. Thus, precocious growth is disallowed during dormancy. The dormant period, which supports robust survival of the aspen tree in winter, is due to loss of access to growth-promoting signals.}, } @article {pmid29519918, year = {2018}, author = {Wang, J and Paesani, S and Ding, Y and Santagati, R and Skrzypczyk, P and Salavrakos, A and Tura, J and Augusiak, R and Mančinska, L and Bacco, D and Bonneau, D and Silverstone, JW and Gong, Q and Acín, A and Rottwitt, K and Oxenløwe, LK and O'Brien, JL and Laing, A and Thompson, MG}, title = {Multidimensional quantum entanglement with large-scale integrated optics.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {285-291}, doi = {10.1126/science.aar7053}, pmid = {29519918}, issn = {1095-9203}, abstract = {The ability to control multidimensional quantum systems is central to the development of advanced quantum technologies. We demonstrate a multidimensional integrated quantum photonic platform able to generate, control, and analyze high-dimensional entanglement. A programmable bipartite entangled system is realized with dimensions up to 15 × 15 on a large-scale silicon photonics quantum circuit. The device integrates more than 550 photonic components on a single chip, including 16 identical photon-pair sources. We verify the high precision, generality, and controllability of our multidimensional technology, and further exploit these abilities to demonstrate previously unexplored quantum applications, such as quantum randomness expansion and self-testing on multidimensional states. Our work provides an experimental platform for the development of multidimensional quantum technologies.}, } @article {pmid29519917, year = {2018}, author = {Zhang, P and Yaji, K and Hashimoto, T and Ota, Y and Kondo, T and Okazaki, K and Wang, Z and Wen, J and Gu, GD and Ding, H and Shin, S}, title = {Observation of topological superconductivity on the surface of an iron-based superconductor.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {182-186}, doi = {10.1126/science.aan4596}, pmid = {29519917}, issn = {1095-9203}, abstract = {Topological superconductors are predicted to host exotic Majorana states that obey non-Abelian statistics and can be used to implement a topological quantum computer. Most of the proposed topological superconductors are realized in difficult-to-fabricate heterostructures at very low temperatures. By using high-resolution spin-resolved and angle-resolved photoelectron spectroscopy, we find that the iron-based superconductor FeTe1-x Se x (x = 0.45; superconducting transition temperature Tc = 14.5 kelvin) hosts Dirac-cone-type spin-helical surface states at the Fermi level; the surface states exhibit an s-wave superconducting gap below Tc Our study shows that the surface states of FeTe0.55Se0.45 are topologically superconducting, providing a simple and possibly high-temperature platform for realizing Majorana states.}, } @article {pmid29519916, year = {2018}, author = {Thaiss, CA and Levy, M and Grosheva, I and Zheng, D and Soffer, E and Blacher, E and Braverman, S and Tengeler, AC and Barak, O and Elazar, M and Ben-Zeev, R and Lehavi-Regev, D and Katz, MN and Pevsner-Fischer, M and Gertler, A and Halpern, Z and Harmelin, A and Aamar, S and Serradas, P and Grosfeld, A and Shapiro, H and Geiger, B and Elinav, E}, title = {Hyperglycemia drives intestinal barrier dysfunction and risk for enteric infection.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1376-1383}, doi = {10.1126/science.aar3318}, pmid = {29519916}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; //European Research Council/International ; }, mesh = {Animals ; Blood Glucose/*metabolism ; Caco-2 Cells ; Cellular Reprogramming ; Citrobacter rodentium ; Diabetes Mellitus, Experimental/*physiopathology ; Enteropathogenic Escherichia coli ; Escherichia coli Infections/*physiopathology ; Gastrointestinal Microbiome ; Gene Deletion ; Glucose/metabolism/pharmacology ; Glucose Transporter Type 2/genetics ; Humans ; Hyperglycemia/*physiopathology ; Intestinal Diseases/*microbiology/*physiopathology ; Intestinal Mucosa/microbiology/physiopathology ; Mice ; Mice, Inbred Strains ; Obesity/physiopathology ; Permeability ; Receptors, Leptin/genetics ; Streptozocin ; }, abstract = {Obesity, diabetes, and related manifestations are associated with an enhanced, but poorly understood, risk for mucosal infection and systemic inflammation. Here, we show in mouse models of obesity and diabetes that hyperglycemia drives intestinal barrier permeability, through GLUT2-dependent transcriptional reprogramming of intestinal epithelial cells and alteration of tight and adherence junction integrity. Consequently, hyperglycemia-mediated barrier disruption leads to systemic influx of microbial products and enhanced dissemination of enteric infection. Treatment of hyperglycemia, intestinal epithelial-specific GLUT2 deletion, or inhibition of glucose metabolism restores barrier function and bacterial containment. In humans, systemic influx of intestinal microbiome products correlates with individualized glycemic control, indicated by glycated hemoglobin levels. Together, our results mechanistically link hyperglycemia and intestinal barrier function with systemic infectious and inflammatory consequences of obesity and diabetes.}, } @article {pmid29519915, year = {2018}, author = {Schuller, JM and Falk, S and Fromm, L and Hurt, E and Conti, E}, title = {Structure of the nuclear exosome captured on a maturing preribosome.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {219-222}, doi = {10.1126/science.aar5428}, pmid = {29519915}, issn = {1095-9203}, mesh = {Cell Nucleus/chemistry/ultrastructure ; Cryoelectron Microscopy ; DEAD-box RNA Helicases/chemistry/ultrastructure ; Exosome Multienzyme Ribonuclease Complex/*chemistry/ultrastructure ; Exosomes/*chemistry/ultrastructure ; Protein Conformation ; RNA Precursors/chemistry/ultrastructure ; RNA, Ribosomal/chemistry/ultrastructure ; RNA, Ribosomal, 5.8S/chemistry/ultrastructure ; Ribosomes/*chemistry/*metabolism/ultrastructure ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/ultrastructure ; }, abstract = {The RNA exosome complex processes and degrades a wide range of transcripts, including ribosomal RNAs (rRNAs). We used cryo-electron microscopy to visualize the yeast nuclear exosome holocomplex captured on a precursor large ribosomal subunit (pre-60S) during 7S-to-5.8S rRNA processing. The cofactors of the nuclear exosome are sandwiched between the ribonuclease core complex (Exo-10) and the remodeled "foot" structure of the pre-60S particle, which harbors the 5.8S rRNA precursor. The exosome-associated helicase Mtr4 recognizes the preribosomal substrate by docking to specific sites on the 25S rRNA, captures the 3' extension of the 5.8S rRNA, and channels it toward Exo-10. The structure elucidates how the exosome forms a structural and functional unit together with its massive pre-60S substrate to process rRNA during ribosome maturation.}, } @article {pmid29519914, year = {2018}, author = {Braunger, K and Pfeffer, S and Shrimal, S and Gilmore, R and Berninghausen, O and Mandon, EC and Becker, T and Förster, F and Beckmann, R}, title = {Structural basis for coupling protein transport and N-glycosylation at the mammalian endoplasmic reticulum.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {215-219}, doi = {10.1126/science.aar7899}, pmid = {29519914}, issn = {1095-9203}, support = {R01 GM035687/GM/NIGMS NIH HHS/United States ; //European Research Council/International ; }, mesh = {Cryoelectron Microscopy ; Endoplasmic Reticulum/*metabolism ; Glycosylation ; HEK293 Cells ; Hexosyltransferases/*chemistry/ultrastructure ; Humans ; Membrane Proteins/*chemistry/ultrastructure ; *Models, Molecular ; Protein Conformation ; Protein Transport ; Ribosomes/*chemistry/ultrastructure ; SEC Translocation Channels/*chemistry/ultrastructure ; }, abstract = {Protein synthesis, transport, and N-glycosylation are coupled at the mammalian endoplasmic reticulum by complex formation of a ribosome, the Sec61 protein-conducting channel, and oligosaccharyltransferase (OST). Here we used different cryo-electron microscopy approaches to determine structures of native and solubilized ribosome-Sec61-OST complexes. A molecular model for the catalytic OST subunit STT3A (staurosporine and temperature sensitive 3A) revealed how it is integrated into the OST and how STT3-paralog specificity for translocon-associated OST is achieved. The OST subunit DC2 was placed at the interface between Sec61 and STT3A, where it acts as a versatile module for recruitment of STT3A-containing OST to the ribosome-Sec61 complex. This detailed structural view on the molecular architecture of the cotranslational machinery for N-glycosylation provides the basis for a mechanistic understanding of glycoprotein biogenesis at the endoplasmic reticulum.}, } @article {pmid29519876, year = {2018}, author = {Davies, KM and Blum, TB and Kühlbrandt, W}, title = {Conserved in situ arrangement of complex I and III2 in mitochondrial respiratory chain supercomplexes of mammals, yeast, and plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3024-3029}, pmid = {29519876}, issn = {1091-6490}, mesh = {Animals ; Asparagus Plant/*metabolism ; Cattle/*metabolism ; Conserved Sequence ; Electron Transport Complex I/*metabolism ; Electron Transport Complex III/*classification/*metabolism ; Gene Expression Regulation ; Species Specificity ; Yarrowia/*metabolism ; }, abstract = {We used electron cryo-tomography and subtomogram averaging to investigate the structure of complex I and its supramolecular assemblies in the inner mitochondrial membrane of mammals, fungi, and plants. Tomographic volumes containing complex I were averaged at ∼4 nm resolution. Principal component analysis indicated that ∼60% of complex I formed a supercomplex with dimeric complex III, while ∼40% were not associated with other respiratory chain complexes. The mutual arrangement of complex I and III2 was essentially conserved in all supercomplexes investigated. In addition, up to two copies of monomeric complex IV were associated with the complex I1III2 assembly in bovine heart and the yeast Yarrowia lipolytica, but their positions varied. No complex IV was detected in the respiratory supercomplex of the plant Asparagus officinalis Instead, an ∼4.5-nm globular protein density was observed on the matrix side of the complex I membrane arm, which we assign to γ-carbonic anhydrase. Our results demonstrate that respiratory chain supercomplexes in situ have a conserved core of complex I and III2, but otherwise their stoichiometry and structure varies. The conserved features of supercomplex assemblies indicate an important role in respiratory electron transfer.}, } @article {pmid29519875, year = {2018}, author = {Hruby, L and Dogra, N and Landini, M and Donner, T and Esslinger, T}, title = {Metastability and avalanche dynamics in strongly correlated gases with long-range interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3279-3284}, pmid = {29519875}, issn = {1091-6490}, abstract = {We experimentally study the stability of a bosonic Mott insulator against the formation of a density wave induced by long-range interactions and characterize the intrinsic dynamics between these two states. The Mott insulator is created in a quantum degenerate gas of 87-Rubidium atoms, trapped in a 3D optical lattice. The gas is located inside and globally coupled to an optical cavity. This causes interactions of global range, mediated by photons dispersively scattered between a transverse lattice and the cavity. The scattering comes with an atomic density modulation, which is measured by the photon flux leaking from the cavity. We initialize the system in a Mott-insulating state and then rapidly increase the global coupling strength. We observe that the system falls into either of two distinct final states. One is characterized by a low photon flux, signaling a Mott insulator, and the other is characterized by a high photon flux, which we associate with a density wave. Ramping the global coupling slowly, we observe a hysteresis loop between the two states-a further signature of metastability. A comparison with a theoretical model confirms that the metastability originates in the competition between short- and global-range interactions. From the increasing photon flux monitored during the switching process, we find that several thousand atoms tunnel to a neighboring site on the timescale of the single-particle dynamics. We argue that a density modulation, initially forming in the compressible surface of the trapped gas, triggers an avalanche tunneling process in the Mott-insulating region.}, } @article {pmid29518561, year = {2018}, author = {Bentlage, B and Osborn, KJ and Lindsay, DJ and Hopcroft, RR and Raskoff, KA and Collins, AG}, title = {Loss of metagenesis and evolution of a parasitic life style in a group of open-ocean jellyfish.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {50-59}, doi = {10.1016/j.ympev.2018.02.030}, pmid = {29518561}, issn = {1095-9513}, mesh = {Animals ; *Biological Evolution ; Larva/physiology ; *Life Cycle Stages ; Likelihood Functions ; *Oceans and Seas ; Parasites/growth & development ; Phylogeny ; Probability ; Scyphozoa/classification/*growth & development/*physiology ; }, abstract = {Loss or stark reduction of the free-swimming medusa or jellyfish stage is common in the cnidarian class Hydrozoa. In the hydrozoan clade Trachylina, however, many species do not possess a sessile polyp or hydroid stage. Trachylines inhabiting freshwater and coastal ecosystems (i.e., Limnomedusae) possess a metagenetic life cycle involving benthic, sessile polyp and free-swimming medusa. In contrast, the paradigm is that open ocean inhabiting, oceanic trachylines (in the orders Narcomedusae and Trachymedusae) develop from zygote to medusa via a free-swimming larva, forgoing the polyp stage. In some open-ocean trachylines, development includes a sessile stage that is an ecto- or endoparasite of other oceanic organisms. We expand the molecular-based phylogenetic hypothesis of trachylines significantly, increasing taxon and molecular marker sampling. Using this comprehensive phylogenetic hypothesis in conjunction with character state reconstructions we enhance understanding of the evolution of life cycles in trachyline hydrozoans. We find that the polyp stage was lost at least twice independently, concurrent with a transition to an oceanic life style. Further, a sessile, polypoid parasitic stage arose once, rather than twice as current classification would imply, in the open ocean inhabiting Narcomedusae. Our results also support the hypothesis that interstitial species of the order Actinulida are directly descended from direct developing, oceanic trachylines.}, } @article {pmid29518377, year = {2018}, author = {Wang, Y and Berger, J and Moussian, B}, title = {Trynity models a tube valve in the Drosophila larval airway system.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {75-83}, doi = {10.1016/j.ydbio.2018.02.019}, pmid = {29518377}, issn = {1095-564X}, mesh = {Animals ; Drosophila ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Embryo, Nonmammalian ; Larva/*metabolism ; Organogenesis/genetics/*physiology ; Trachea/*embryology/metabolism ; }, abstract = {Terminal differentiation of an organ is the last step in development that enables the organism to survive in the outside world after birth. Terminal differentiation of the insect tracheae that ends with filling the tubular network with gas is not fully understood at the tissue level. Here, we demonstrate that yet unidentified valves at the end of the tracheal system of the fruit fly Drosophila melanogaster embryo are important elements allowing terminal differentiation of this organ. Formation of these valves depends on the function of the zona pellucida protein Trynity (Tyn). The tracheae of tyn mutant embryos that lack these structures do not fill with gas. Additionally, external material penetrates into the tracheal tubes indicating that the tyn spiracles are permanently open. We conclude that the tracheal endings have to be closed to ensure gas-filling. We speculate that according to physical models closing of the tubular tracheal network provokes initial increase of the internal hydrostatic pressure necessary for gas generation through cavitation when the pressure is subsequently decreased.}, } @article {pmid29518376, year = {2018}, author = {Moore, KB and Logan, MA and Aldiri, I and Roberts, JM and Steele, M and Vetter, ML}, title = {C8orf46 homolog encodes a novel protein Vexin that is required for neurogenesis in Xenopus laevis.}, journal = {Developmental biology}, volume = {437}, number = {1}, pages = {27-40}, pmid = {29518376}, issn = {1095-564X}, support = {R01 EY012274/EY/NEI NIH HHS/United States ; R21 EY017650/EY/NEI NIH HHS/United States ; T32 EY024234/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/*genetics ; Blotting, Western ; Cell Differentiation/genetics ; Cyclin-Dependent Kinase Inhibitor p27/metabolism ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Mice ; Nerve Tissue Proteins/metabolism ; Neural Plate/embryology/metabolism ; Neurogenesis/*genetics ; Retina/embryology/metabolism ; Xenopus Proteins/*genetics ; Xenopus laevis ; }, abstract = {Neural basic helix-loop helix (bHLH) transcription factors promote progenitor cell differentiation by activation of downstream target genes that coordinate neuronal differentiation. Here we characterize a neural bHLH target gene in Xenopus laevis, vexin (vxn; previously sbt1), that is homologous to human c8orf46 and is conserved across vertebrate species. C8orf46 has been implicated in cancer progression, but its function is unknown. Vxn is transiently expressed in differentiating progenitors in the developing central nervous system (CNS), and is required for neurogenesis in the neural plate and retina. Its function is conserved, since overexpression of either Xenopus or mouse vxn expands primary neurogenesis and promotes early retinal cell differentiation in cooperation with neural bHLH factors. Vxn protein is localized to the cell membrane and the nucleus, but functions in the nucleus to promote neural differentiation. Vxn inhibits cell proliferation, and works with the cyclin-dependent kinase inhibitor p27Xic1 (cdkn1b) to enhance neurogenesis and increase levels of the proneural protein Neurog2. We propose that vxn provides a key link between neural bHLH activity and execution of the neurogenic program.}, } @article {pmid29518280, year = {2018}, author = {Lane, JE and McAdam, AG and McFarlane, SE and Williams, CT and Humphries, MM and Coltman, DW and Gorrell, JC and Boutin, S}, title = {Phenological shifts in North American red squirrels: disentangling the roles of phenotypic plasticity and microevolution.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {810-821}, doi = {10.1111/jeb.13263}, pmid = {29518280}, issn = {1420-9101}, abstract = {Phenological shifts are the most widely reported ecological responses to climate change, but the requirements to distinguish their causes (i.e. phenotypic plasticity vs. microevolution) are rarely met. To do so, we analysed almost two decades of parturition data from a wild population of North American red squirrels (Tamiasciurus hudsonicus). Although an observed advance in parturition date during the first decade provided putative support for climate change-driven microevolution, a closer look revealed a more complex pattern. Parturition date was heritable [h2 = 0.14 (0.07-0.21 (HPD interval)] and under phenotypic selection [β = -0.14 ± 0.06 (SE)] across the full study duration. However, the early advance reversed in the second decade. Further, selection did not act on the genetic contribution to variation in parturition date, and observed changes in predicted breeding values did not exceed those expected due to genetic drift. Instead, individuals responded plastically to environmental variation, and high food [white spruce (Picea glauca) seed] production in the first decade appears to have produced a plastic advance. In addition, there was little evidence of climate change affecting the advance, as there was neither a significant influence of spring temperature on parturition date or evidence of a change in spring temperatures across the study duration. Heritable traits not responding to selection in accordance with quantitative genetic predictions have long presented a puzzle to evolutionary ecologists. Our results on red squirrels provide empirical support for one potential solution: phenotypic selection arising from an environmental, as opposed to genetic, covariance between the phenotypic trait and annual fitness.}, } @article {pmid29518274, year = {2018}, author = {Halbritter, AH and Fior, S and Keller, I and Billeter, R and Edwards, PJ and Holderegger, R and Karrenberg, S and Pluess, AR and Widmer, A and Alexander, JM}, title = {Trait differentiation and adaptation of plants along elevation gradients.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {6}, pages = {784-800}, doi = {10.1111/jeb.13262}, pmid = {29518274}, issn = {1420-9101}, abstract = {Studies of genetic adaptation in plant populations along elevation gradients in mountains have a long history, but there has until now been neither a synthesis of how frequently plant populations exhibit adaptation to elevation nor an evaluation of how consistent underlying trait differences across species are. We reviewed studies of adaptation along elevation gradients (i) from a meta-analysis of phenotypic differentiation of three traits (height, biomass and phenology) from plants growing in 70 common garden experiments; (ii) by testing elevation adaptation using three fitness proxies (survival, reproductive output and biomass) from 14 reciprocal transplant experiments; (iii) by qualitatively assessing information at the molecular level, from 10 genomewide surveys and candidate gene approaches. We found that plants originating from high elevations were generally shorter and produced less biomass, but phenology did not vary consistently. We found significant evidence for elevation adaptation in terms of survival and biomass, but not for reproductive output. Variation in phenotypic and fitness responses to elevation across species was not related to life history traits or to environmental conditions. Molecular studies, which have focussed mainly on loci related to plant physiology and phenology, also provide evidence for adaptation along elevation gradients. Together, these studies indicate that genetically based trait differentiation and adaptation to elevation are widespread in plants. We conclude that a better understanding of the mechanisms underlying adaptation, not only to elevation but also to environmental change, will require more studies combining the ecological and molecular approaches.}, } @article {pmid29518262, year = {2018}, author = {Wilson, LAB}, title = {The evolution of ontogenetic allometric trajectories in mammalian domestication.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {867-877}, doi = {10.1111/evo.13464}, pmid = {29518262}, issn = {1558-5646}, abstract = {Morphological divergence of domesticated as compared to wild forms must result from changes in the ontogenetic process. Species-specific tests for heterochrony have rejected a single explanation of domestic forms representing juveniles of their wild relatives. Ontogenetic allometric trajectories for 12 pairs of wild and domestic mammals were examined using skull growth data for 1070 specimens, including representatives from all lineages in which domestication has occurred. A suite of tests were performed to quantify allometric disparity in wild and domestic forms and assess the extent and patterning of modification to allometric trajectories. Domestication has modified postnatal ontogenetic allometric trajectories in mammals, and has generated disparity, achieved through lengthening of trajectory slopes and alteration to slope angles. Allometric disparity was similar for domestic forms compared to their wild relatives, whereas the magnitude of dispersion along allometric vectors differed between precocial mammals and altricial mammals, underscoring the importance of life history and shared evolutionary history in patterns of ontogenetic variation. The results verify the importance of scaling in the morphological changes associated with domestication. The response to domestication for all measured trajectory parameters was variable across species, suggesting multiple pathways of change.}, } @article {pmid29518255, year = {2018}, author = {Hunter, DC and Pemberton, JM and Pilkington, JG and Morrissey, MB}, title = {Quantification and decomposition of environment-selection relationships.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {851-866}, doi = {10.1111/evo.13461}, pmid = {29518255}, issn = {1558-5646}, abstract = {In nature, selection varies across time in most environments, but we lack an understanding of how specific ecological changes drive this variation. Ecological factors can alter phenotypic selection coefficients through changes in trait distributions or individual mean fitness, even when the trait-absolute fitness relationship remains constant. We apply and extend a regression-based approach in a population of Soay sheep (Ovis aries) and suggest metrics of environment-selection relationships that can be compared across studies. We then introduce a novel method that constructs an environmentally structured fitness function. This allows calculation of full (as in existing approaches) and partial (acting separately through the absolute fitness function slope, mean fitness, and phenotype distribution) sensitivities of selection to an ecological variable. Both approaches show positive overall effects of density on viability selection of lamb mass. However, the second approach demonstrates that this relationship is largely driven by effects of density on mean fitness, rather than on the trait-fitness relationship slope. If such mechanisms of environmental dependence of selection are common, this could have important implications regarding the frequency of fluctuating selection, and how previous selection inferences relate to longer term evolutionary dynamics.}, } @article {pmid29518227, year = {2018}, author = {Ralf, A and Montiel González, D and Zhong, K and Kayser, M}, title = {Yleaf: Software for Human Y-Chromosomal Haplogroup Inference from Next-Generation Sequencing Data.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1291-1294}, doi = {10.1093/molbev/msy032}, pmid = {29518227}, issn = {1537-1719}, abstract = {Next-generation sequencing (NGS) technologies offer immense possibilities given the large genomic data they simultaneously deliver. The human Y-chromosome serves as good example how NGS benefits various applications in evolution, anthropology, genealogy, and forensics. Prior to NGS, the Y-chromosome phylogenetic tree consisted of a few hundred branches, based on NGS data, it now contains many thousands. The complexity of both, Y tree and NGS data provide challenges for haplogroup assignment. For effective analysis and interpretation of Y-chromosome NGS data, we present Yleaf, a publically available, automated, user-friendly software for high-resolution Y-chromosome haplogroup inference independently of library and sequencing methods.}, } @article {pmid29518196, year = {2018}, author = {Graupner, N and Jensen, M and Bock, C and Marks, S and Rahmann, S and Beisser, D and Boenigk, J}, title = {Evolution of heterotrophy in chrysophytes as reflected by comparative transcriptomics.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, pmid = {29518196}, issn = {1574-6941}, abstract = {Shifts in the nutritional mode between phototrophy, mixotrophy and heterotrophy are a widespread phenomenon in the evolution of eukaryotic diversity. The transition between nutritional modes is particularly pronounced in chrysophytes and occurred independently several times through parallel evolution. Thus, chrysophytes provide a unique opportunity for studying the molecular basis of nutritional diversification and of the accompanying pathway reduction and degradation of plastid structures. In order to analyze the succession in switching the nutritional mode from mixotrophy to heterotrophy, we compared the transcriptome of the mixotrophic Poterioochromonas malhamensis with the transcriptomes of three obligate heterotrophic species of Ochromonadales. We used the transcriptome of P. malhamensis as a reference for plastid reduction in the heterotrophic taxa. The analyzed heterotrophic taxa were in different stages of plastid reduction. We investigated the reduction of several photosynthesis related pathways e.g. the xanthophyll cycle, the mevalonate pathway, the shikimate pathway and the tryptophan biosynthesis as well as the reduction of plastid structures and postulate a presumable succession of pathway reduction and degradation of accompanying structures.}, } @article {pmid29518190, year = {2018}, author = {Buttet, GF and Murray, AM and Goris, T and Burion, M and Jin, B and Rolle, M and Holliger, C and Maillard, J}, title = {Coexistence of two distinct Sulfurospirillum populations respiring tetrachloroethene-genomic and kinetic considerations.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy018}, pmid = {29518190}, issn = {1574-6941}, abstract = {Two anaerobic bacterial consortia, each harboring a distinct Sulfurospirillum population, were derived from a 10 year old consortium, SL2, previously characterized for the stepwise dechlorination of tetrachloroethene (PCE) to cis-dichloroethene (cis-DCE) via accumulation of trichloroethene (TCE). Population SL2-1 dechlorinated PCE to TCE exclusively, while SL2-2 produced cis-DCE from PCE without substantial TCE accumulation. The reasons explaining the long-term coexistence of the populations were investigated. Genome sequencing revealed a novel Sulfurospirillum species, designated 'Candidatus Sulfurospirillum diekertiae', whose genome differed significantly from other Sulfurospirillum spp. (78%-83% ANI). Genome-wise, SL2-1 and SL2-2 populations are almost identical, but differences in their tetrachloroethene reductive dehalogenase sequences explain the distinct dechlorination patterns. An extended series of batch cultures were performed at PCE concentrations of 2-200 μM. A model was developed to determine their dechlorination kinetic parameters. The affinity constant and maximal growth rate differ between the populations: the affinity is 6- to 8-fold higher and the growth rate 5-fold lower for SL2-1 than SL2-2. Mixed cultivation of the enriched populations at 6 and 30 μM PCE showed that a low PCE concentration could be the driving force for both functional diversity of reductive dehalogenases and niche specialization of organohalide-respiring bacteria with overlapping substrate ranges.}, } @article {pmid29517482, year = {2018}, author = {Penkhrue, W and Sujarit, K and Kudo, T and Ohkuma, M and Masaki, K and Aizawa, T and Pathom-Aree, W and Khanongnuch, C and Lumyong, S}, title = {Amycolatopsis oliviviridis sp. nov., a novel polylactic acid-bioplastic-degrading actinomycete isolated from paddy soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1448-1454}, doi = {10.1099/ijsem.0.002682}, pmid = {29517482}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Polyesters/*metabolism ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel bioplastic-degrading actinomycete, strain SCM_MK2-4T, was isolated from paddy soil in Thailand. The 16S rRNA gene sequence showed that strain SCM_MK2-4T belonged to the genus Amycolatopsis, with the highest sequence similarity to Amycolatopsisazurea JCM 3275T (99.4 %), and was phylogenetically clustered with this strain along with Amycolatopsislurida JCM 3141T (99.3 %), A. japonica DSM 44213T (99.2 %), A. decaplanina DSM 44594T (99.0 %), A. roodepoortensis M29T (98.9 %), A. keratiniphilasubsp. nogabecina DSM 44586T (98.8 %), A. keratiniphilasubsp. keratiniphila DSM 44409T (98.5 %), A. orientalis DSM 40040T (98.4 %) and A. regifaucium GY080T (98.3 %). A combination of DNA-DNA hybridization results ranging from 42.8±3.2 to 66.2±1.4 % with the type strains of A. azurea and A. lurida and some different phenotypic characteristics indicated that the strain could be distinguished from its closest phylogenetic neighbours. Whole-cell hydrolysates of the strain were shown to contain meso-diaminopimelic acid, arabinose, galactose, glucose, ribose, mannose, rhamnose and xylose. The predominant menaquinone was MK-9(H4). The major cellular fatty acid profile consisted of iso-C15 : 0, iso-C16 : 0, summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2OH) and C16 : 0. The polar lipid composition of the strain consisted of phosphatidyl-N-methylethylethanolamine, phosphatidylethanolamine, hydroxyphosphatidylethanolamine, phosphatidylglycerol, aminophospholipids, an unidentified phospholipid and two unidentified glycolipids. The G+C content of the genomic DNA was 68.2 mol%. On the basis of phylogenetic analyses, DNA-DNA hybridization experimentation and the phenotypic characteristics, it was concluded that strain SCM_MK2-4T represents a novel species of the genus Amycolatopsis, for which the name Amycolatopsis oliviviridis sp. nov. is proposed. The type strain is SCM_MK2-4T (=TBRC 7186T=JCM 32134T).}, } @article {pmid29517475, year = {2018}, author = {Dorofeeva, LV and Starodumova, IP and Krauzova, VI and Prisyazhnaya, NV and Vinokurova, NG and Lysanskaya, VY and Tarlachkov, SV and Evtushenko, LI}, title = {Rathayibacter oskolensis sp. nov., a novel actinobacterium from Androsace koso-poljanskii Ovcz. (Primulaceae) endemic to the Central Russian Upland.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {5}, pages = {1442-1447}, doi = {10.1099/ijsem.0.002681}, pmid = {29517475}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Nucleic Acid Hybridization ; *Phylogeny ; Primulaceae/*microbiology ; RNA, Ribosomal, 16S/genetics ; Russia ; Sequence Analysis, DNA ; }, abstract = {A rod-shaped, non-endospore-forming and non-motile bacterium, strain DL-329T, was isolated from the above-ground part of a plant, Androsace koso-poljanskii Ovcz. (Primulaceae), at the the State Natural Reserve 'Belogorie', Russia. On the basis of 16S rRNA gene sequence comparisons, the strain clustered with members of the genus Rathayibacter, showing the highest sequence similarity to Rathayibacter tritici (98.89 %), Rathayibacter rathayi (98.82 %) and Rathayibacter festucae (98.82 %). The DNA hybridization experiments demonstrated that strain DL-329T represents a separate genomic species. The results of comparative studies of physiological and chemotaxonomic characteristics, including cell-wall sugar patterns, polar lipid profiles, and the matrix-assisted laser desorption/ionization time-of-flight mass spectra of bacterial cells, allowed clear differentiation of VKM Ac-2121T from the recognized Rathayibacter species at the phenotypic level. Based on the data obtained, a new species, Rathayibacter oskolensis sp. nov., is proposed, with DL-329T (=VKM Ac-2121T=LMG 22542T) as the type strain.}, } @article {pmid29517047, year = {2018}, author = {}, title = {'March for Science' organizers hope to repeat last year's success.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {276}, doi = {10.1038/d41586-018-02748-x}, pmid = {29517047}, issn = {1476-4687}, } @article {pmid29517046, year = {2018}, author = {Drew, L}, title = {Fighting the inevitability of ageing.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S15-S17}, doi = {10.1038/d41586-018-02479-z}, pmid = {29517046}, issn = {1476-4687}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aging/genetics/*physiology ; Animals ; Diet, High-Protein ; Drosophila melanogaster/genetics/physiology ; Female ; Hand Strength ; History, 20th Century ; History, 21st Century ; Humans ; Independent Living ; Male ; Middle Aged ; Muscle, Skeletal/physiology/*physiopathology ; Myostatin/antagonists & inhibitors/metabolism ; Quality of Life ; Rejuvenation/physiology ; Resistance Training ; Sarcopenia/diagnosis/physiopathology/*prevention & control/*therapy ; Walking Speed ; }, } @article {pmid29517045, year = {2018}, author = {}, title = {Isolation and alienation force women from technology positions.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {276}, doi = {10.1038/d41586-018-02749-w}, pmid = {29517045}, issn = {1476-4687}, } @article {pmid29517044, year = {2018}, author = {Gibney, E}, title = {Surprise graphene discovery could unlock secrets of superconductivity.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {151-152}, doi = {10.1038/d41586-018-02773-w}, pmid = {29517044}, issn = {1476-4687}, } @article {pmid29517043, year = {2018}, author = {Hodson, R}, title = {The future of medicine.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S1}, doi = {10.1038/d41586-018-02472-6}, pmid = {29517043}, issn = {1476-4687}, mesh = {Aging/physiology ; Anti-Bacterial Agents/supply & distribution ; Autoimmune Diseases/prevention & control/therapy ; Drug Discovery ; Gastrointestinal Microbiome ; Gene Editing ; Humans ; Infant, Newborn ; Infection/drug therapy/epidemiology ; Medicine/*trends ; Paralysis/rehabilitation/therapy ; }, } @article {pmid29517041, year = {2018}, author = {Efferson, C and Fehr, E}, title = {Simple moral code supports cooperation.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {169-170}, doi = {10.1038/d41586-018-02621-x}, pmid = {29517041}, issn = {1476-4687}, mesh = {*Interpersonal Relations ; *Morals ; }, } @article {pmid29517040, year = {2018}, author = {Gilbert, N}, title = {Four stories of antibacterial breakthroughs.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S5-S7}, doi = {10.1038/d41586-018-02475-3}, pmid = {29517040}, issn = {1476-4687}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology/*supply & distribution ; Bacteria/drug effects/enzymology/pathogenicity ; CRISPR-Cas Systems/genetics ; Ceftizoxime/analogs & derivatives/chemistry/metabolism/pharmacology ; Clinical Trials as Topic ; DNA-Directed RNA Polymerases/metabolism ; Depsipeptides/pharmacology ; *Drug Resistance, Microbial/drug effects ; Drug Resistance, Multiple, Bacterial/drug effects ; Gene Editing ; Humans ; Mice ; Molecular Targeted Therapy ; Rifamycins/pharmacology ; beta-Lactamases/metabolism ; }, } @article {pmid29517038, year = {2018}, author = {Butler, D}, title = {EU expected to vote on pesticide ban after major scientific review.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {150-151}, doi = {10.1038/d41586-018-02639-1}, pmid = {29517038}, issn = {1476-4687}, mesh = {Animals ; Bees/*drug effects ; Conservation of Natural Resources/*legislation & jurisprudence ; Ecosystem ; *European Union ; *Legislation, Drug ; Neonicotinoids/*adverse effects ; Pesticides/*adverse effects ; }, } @article {pmid29517037, year = {2018}, author = {}, title = {Chinese project offers a brighter farming future.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {141}, doi = {10.1038/d41586-018-02742-3}, pmid = {29517037}, issn = {1476-4687}, mesh = {China ; Conservation of Natural Resources/methods/*trends ; Crop Production/*methods/statistics & numerical data/*trends ; Efficiency, Organizational/*statistics & numerical data/*trends ; Farms/organization & administration/trends ; Politics ; }, } @article {pmid29517036, year = {2018}, author = {Witze, A}, title = {US scientists plot return to the Moon's surface.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {149-150}, doi = {10.1038/d41586-018-02697-5}, pmid = {29517036}, issn = {1476-4687}, mesh = {Astronauts ; Extraterrestrial Environment/chemistry ; *Moon ; *Research Personnel ; Space Flight/economics/instrumentation/*legislation & jurisprudence/*trends ; Spacecraft ; United States ; United States National Aeronautics and Space Administration/economics/*legislation & jurisprudence ; Water/analysis ; }, } @article {pmid29517035, year = {2018}, author = {King, A}, title = {A CRISPR edit for heart disease.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S23-S25}, doi = {10.1038/d41586-018-02482-4}, pmid = {29517035}, issn = {1476-4687}, mesh = {Amino Acid Substitution ; Angiopoietin-like Proteins/deficiency/genetics ; Animals ; Antibodies, Monoclonal/pharmacology/therapeutic use ; Apolipoprotein B-100/deficiency/genetics ; Apolipoproteins C/genetics ; CRISPR-Cas Systems/*genetics ; Cholesterol, LDL/blood ; Disease Models, Animal ; Dystrophin/genetics/metabolism ; Gene Editing/*methods/*trends ; Genetic Therapy/*methods/*trends ; Heart Diseases/blood/*genetics/*prevention & control/therapy ; Humans ; Hypercholesterolemia/blood/genetics/prevention & control ; Lipoprotein(a)/deficiency/genetics ; Mice ; Muscular Dystrophy, Duchenne/genetics/therapy ; Mutation ; Myocardial Ischemia/drug therapy/genetics/prevention & control ; Patient Safety ; Proprotein Convertase 9/antagonists & inhibitors/genetics/metabolism ; Stroke/drug therapy/genetics/prevention & control ; }, } @article {pmid29517034, year = {2018}, author = {}, title = {Learn to tell science stories.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {141-142}, doi = {10.1038/d41586-018-02740-5}, pmid = {29517034}, issn = {1476-4687}, mesh = {Climate Change ; *Forecasting ; *Literature, Modern ; *Narration ; *Research Personnel ; Science/*trends ; Social Change ; }, } @article {pmid29517033, year = {2018}, author = {Sinkjær, T}, title = {Fund ideas, not pedigree, to find fresh insight.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {143}, doi = {10.1038/d41586-018-02743-2}, pmid = {29517033}, issn = {1476-4687}, mesh = {*Creativity ; *Data Anonymization ; *Diffusion of Innovation ; Financing, Organized/*economics/*organization & administration ; Focus Groups ; Peer Review, Research/*methods/trends ; *Research Personnel/economics/psychology/standards ; }, } @article {pmid29517032, year = {2018}, author = {Cyranoski, D}, title = {China tests giant air cleaner to combat smog.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {152-153}, doi = {10.1038/d41586-018-02704-9}, pmid = {29517032}, issn = {1476-4687}, mesh = {Air Pollutants/adverse effects/chemistry/*isolation & purification ; Air Pollution/adverse effects/economics/prevention & control ; China ; Humans ; Nitrogen Oxides/adverse effects/isolation & purification ; Smog/adverse effects/*prevention & control ; Uncertainty ; }, } @article {pmid29517031, year = {2018}, author = {Tollefson, J}, title = {Latest US weather satellite highlights forecasting challenges.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {154}, doi = {10.1038/d41586-018-02630-w}, pmid = {29517031}, issn = {1476-4687}, } @article {pmid29517030, year = {2018}, author = {Dolgin, E}, title = {Bringing down the cost of cancer treatment.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S26-S29}, doi = {10.1038/d41586-018-02483-3}, pmid = {29517030}, issn = {1476-4687}, mesh = {*Cost Control ; *Cost-Benefit Analysis ; *Costs and Cost Analysis ; Health Care Costs ; Neoplasms/economics/*therapy ; }, } @article {pmid29517029, year = {2018}, author = {}, title = {Penguin colony, integrity office and Curiosity's arm.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {146-147}, doi = {10.1038/d41586-018-02744-1}, pmid = {29517029}, issn = {1476-4687}, } @article {pmid29517028, year = {2018}, author = {D'Angelo, E and Mazzarello, P}, title = {Electric fish inspire inventors across the centuries.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {165}, doi = {10.1038/d41586-018-02832-2}, pmid = {29517028}, issn = {1476-4687}, mesh = {Animals ; *Electric Fish ; *Inventors ; }, } @article {pmid29517027, year = {2018}, author = {Sibley, DR and Shi, L}, title = {A new era of rationally designed antipsychotics.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {170-172}, pmid = {29517027}, issn = {1476-4687}, support = {Z01 NS002263-32/NULL/Intramural NIH HHS/United States ; }, mesh = {*Antipsychotic Agents ; *Schizophrenia ; }, } @article {pmid29517026, year = {2018}, author = {Scott, A}, title = {How CRISPR is transforming drug discovery.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S10-S11}, doi = {10.1038/d41586-018-02477-1}, pmid = {29517026}, issn = {1476-4687}, mesh = {Animals ; *CRISPR-Cas Systems ; Disease Models, Animal ; Drug Discovery/*methods/*trends ; Drug Resistance/genetics ; Gene Editing/methods/*trends ; Gene Knockout Techniques ; Humans ; Molecular Targeted Therapy/*trends ; }, } @article {pmid29517025, year = {2018}, author = {Fortney, J}, title = {A deeper look at Jupiter.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {168-169}, doi = {10.1038/d41586-018-02612-y}, pmid = {29517025}, issn = {1476-4687}, } @article {pmid29517024, year = {2018}, author = {Davies, R}, title = {Donald Lynden-Bell (1935-2018).}, journal = {Nature}, volume = {555}, number = {7695}, pages = {166}, doi = {10.1038/d41586-018-02579-w}, pmid = {29517024}, issn = {1476-4687}, } @article {pmid29517023, year = {2018}, author = {Fiske, P}, title = {Why scientists need to market themselves.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {275-276}, doi = {10.1038/d41586-018-02747-y}, pmid = {29517023}, issn = {1476-4687}, } @article {pmid29517022, year = {2018}, author = {Witze, A}, title = {Attack of the extreme floods.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {156-158}, doi = {10.1038/d41586-018-02745-0}, pmid = {29517022}, issn = {1476-4687}, mesh = {Boston ; Climate Change/economics/*statistics & numerical data ; Cyclonic Storms/economics/statistics & numerical data ; Disasters/economics/*statistics & numerical data ; El Nino-Southern Oscillation ; Floods/economics/*statistics & numerical data ; Florida ; Humans ; London ; New Orleans ; New York City ; Seawater/*analysis ; Water Movements ; Wind ; }, } @article {pmid29517021, year = {2018}, author = {Gruber, K}, title = {Cleaning up pollutants to protect future health.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S20-S22}, doi = {10.1038/d41586-018-02481-5}, pmid = {29517021}, issn = {1476-4687}, mesh = {*Air Pollutants ; Environmental Health ; Humans ; }, } @article {pmid29517020, year = {2018}, author = {Eisenstein, M}, title = {Infection forecasts powered by big data.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S2-S4}, doi = {10.1038/d41586-018-02473-5}, pmid = {29517020}, issn = {1476-4687}, mesh = {Algorithms ; Brazil/epidemiology ; Confidentiality ; Datasets as Topic/*statistics & numerical data ; Dengue/epidemiology/transmission ; Disease Outbreaks/prevention & control/*statistics & numerical data ; Electronic Health Records/statistics & numerical data ; *Epidemiological Monitoring ; Hemorrhagic Fever, Ebola/epidemiology ; Humans ; Incidence ; Infection/*epidemiology/transmission ; Infection Control/methods ; Influenza, Human/epidemiology ; Internet/*statistics & numerical data ; Mobile Applications/statistics & numerical data ; Public Health/*methods/trends ; Self Report ; Smartphone/statistics & numerical data ; Social Media/statistics & numerical data ; Volunteers ; Zika Virus Infection/epidemiology ; }, } @article {pmid29517019, year = {2018}, author = {Owens, B}, title = {Canadian science wins billions in new budget.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {153}, doi = {10.1038/d41586-018-02529-6}, pmid = {29517019}, issn = {1476-4687}, mesh = {Budgets/*legislation & jurisprudence ; Canada ; *Federal Government ; Financing, Organized/economics/legislation & jurisprudence ; Research Personnel/economics/psychology ; Science/*economics/*legislation & jurisprudence ; }, } @article {pmid29517018, year = {2018}, author = {Savage, N}, title = {The mind-reading devices that can free paralysed muscles.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S12-S14}, doi = {10.1038/d41586-018-02478-0}, pmid = {29517018}, issn = {1476-4687}, mesh = {Adult ; Animals ; Brain-Computer Interfaces/*trends ; Electrodes, Implanted ; Epilepsy, Temporal Lobe/physiopathology ; Exoskeleton Device ; Humans ; Male ; Mice ; Middle Aged ; *Movement ; Muscles/*physiology ; Neural Prostheses ; Paralysis/*physiopathology/*rehabilitation ; Robotics/*instrumentation/*trends ; Spinal Cord Injuries/physiopathology ; Stroke/physiopathology ; Touch/physiology ; }, } @article {pmid29517017, year = {2018}, author = {}, title = {Science PhDs lead to enjoyable jobs.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {277}, doi = {10.1038/d41586-018-02696-6}, pmid = {29517017}, issn = {1476-4687}, mesh = {Canada ; Career Mobility ; *Education, Graduate ; Employment/*statistics & numerical data ; *Job Satisfaction ; Salaries and Fringe Benefits/statistics & numerical data ; Science/*education ; Sex Factors ; United Kingdom ; Workforce ; }, } @article {pmid29517016, year = {2018}, author = {Krockenberger, Y and Taniyasu, Y}, title = {Transistors driven by superconductors.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {172-173}, doi = {10.1038/d41586-018-02717-4}, pmid = {29517016}, issn = {1476-4687}, mesh = {Graphite ; *Superconductivity ; *Transistors, Electronic ; }, } @article {pmid29517015, year = {2018}, author = {}, title = {Does your code stand up to scrutiny?.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {142}, doi = {10.1038/d41586-018-02741-4}, pmid = {29517015}, issn = {1476-4687}, mesh = {Algorithms ; Authorship ; *Editorial Policies ; *Peer Review, Research ; *Periodicals as Topic ; Software/*standards ; }, } @article {pmid29517014, year = {2018}, author = {Zizka, A and Antonelli, A}, title = {Mountains of diversity.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {173-174}, doi = {10.1038/d41586-018-02062-6}, pmid = {29517014}, issn = {1476-4687}, } @article {pmid29517013, year = {2018}, author = {DeWeerdt, S}, title = {How baby's first microbes could be crucial to future health.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S18-S19}, doi = {10.1038/d41586-018-02480-6}, pmid = {29517013}, issn = {1476-4687}, mesh = {Adult ; Asthma/microbiology/prevention & control ; Bifidobacterium/metabolism/physiology ; Breast Feeding ; Child, Preschool ; Diabetes Mellitus/microbiology/prevention & control ; Dietary Supplements ; Enterocolitis, Necrotizing/microbiology/prevention & control ; Female ; Gastrointestinal Microbiome/physiology ; *Health ; Humans ; Infant ; Infant, Newborn ; Lactobacillus/physiology ; Lactoferrin/administration & dosage/immunology ; Microbiota/*physiology ; Milk, Human/chemistry/immunology ; Neonatology/*methods/*trends ; Oligosaccharides/administration & dosage/metabolism ; Parturition ; Pregnancy ; Probiotics/administration & dosage ; Proteobacteria/pathogenicity ; }, } @article {pmid29517012, year = {2018}, author = {Brisbois, MC and Girling, K and Findlay, S}, title = {Academics should build rapport with government's policy analysts.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {165}, doi = {10.1038/d41586-018-02831-3}, pmid = {29517012}, issn = {1476-4687}, mesh = {*Government ; Health Policy ; *Public Policy ; }, } @article {pmid29517011, year = {2018}, author = {Bourzac, K}, title = {The battle to tame autoimmunity.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {S8-S9}, doi = {10.1038/d41586-018-02476-2}, pmid = {29517011}, issn = {1476-4687}, mesh = {Animals ; Autoimmune Diseases/*immunology/pathology/prevention & control/*therapy ; Autoimmunity/drug effects/*immunology ; Diabetes Mellitus, Type 1/genetics/immunology/prevention & control/therapy ; Graft Rejection/immunology/prevention & control ; Graft vs Host Disease/immunology/therapy ; Humans ; Mice ; Multiple Sclerosis/immunology/therapy ; T-Lymphocytes, Regulatory/cytology/immunology ; }, } @article {pmid29517010, year = {2018}, author = {Shen, YA and Shoda, Y and Fine, I}, title = {Too few women authors on research papers in leading journals.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {165}, doi = {10.1038/d41586-018-02833-1}, pmid = {29517010}, issn = {1476-4687}, support = {R01 EY014645/EY/NEI NIH HHS/United States ; }, mesh = {*Authorship ; Female ; Humans ; Periodicals as Topic ; Publishing ; *Research ; }, } @article {pmid29517009, year = {2018}, author = {}, title = {Correction.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {154}, doi = {10.1038/d41586-018-02836-y}, pmid = {29517009}, issn = {1476-4687}, } @article {pmid29517008, year = {2018}, author = {Sekhar, A}, title = {Gender parity closer among astronomers in low-income countries.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {165}, doi = {10.1038/d41586-018-02835-z}, pmid = {29517008}, issn = {1476-4687}, mesh = {Astronomy/*economics ; Developing Countries ; Female ; Humans ; Income ; *Poverty ; *Sexism ; Socioeconomic Factors ; }, } @article {pmid29517007, year = {2018}, author = {Hussain, SA and Nayak, VC and Menezes, RG}, title = {India and Pakistan should work together for water security.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {165}, doi = {10.1038/d41586-018-02834-0}, pmid = {29517007}, issn = {1476-4687}, mesh = {India ; Pakistan ; *Water ; *Water Supply ; }, } @article {pmid29517005, year = {2018}, author = {Fyfe, A and Røstvik, CM}, title = {How female fellows fared at the Royal Society.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {159-161}, doi = {10.1038/d41586-018-02746-z}, pmid = {29517005}, issn = {1476-4687}, mesh = {Archives ; Authorship/*history ; History, 20th Century ; History, 21st Century ; London ; Peer Review, Research ; Periodicals as Topic/*history ; Sex Distribution ; Sexism/*history/trends ; Societies, Scientific/*history/*organization & administration/trends ; }, } @article {pmid29517004, year = {2018}, author = {Gurevitch, J and Koricheva, J and Nakagawa, S and Stewart, G}, title = {Meta-analysis and the science of research synthesis.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {175-182}, pmid = {29517004}, issn = {1476-4687}, mesh = {Animals ; Biological Evolution ; Biological Science Disciplines/*methods ; Ecology/methods ; History, 20th Century ; History, 21st Century ; *Meta-Analysis as Topic ; *Research/history/trends ; }, abstract = {Meta-analysis is the quantitative, scientific synthesis of research results. Since the term and modern approaches to research synthesis were first introduced in the 1970s, meta-analysis has had a revolutionary effect in many scientific fields, helping to establish evidence-based practice and to resolve seemingly contradictory research outcomes. At the same time, its implementation has engendered criticism and controversy, in some cases general and others specific to particular disciplines. Here we take the opportunity provided by the recent fortieth anniversary of meta-analysis to reflect on the accomplishments, limitations, recent advances and directions for future developments in the field of research synthesis.}, } @article {pmid29517003, year = {2018}, author = {Tukiainen, T and Villani, AC and Yen, A and Rivas, MA and Marshall, JL and Satija, R and Aguirre, M and Gauthier, L and Fleharty, M and Kirby, A and Cummings, BB and Castel, SE and Karczewski, KJ and Aguet, F and Byrnes, A and Consortium, G and Lappalainen, T and Regev, A and Ardlie, KG and Hacohen, N and MacArthur, DG}, title = {Corrigendum: Landscape of X chromosome inactivation across human tissues.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {274}, pmid = {29517003}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24265.}, } @article {pmid29517002, year = {2018}, author = {Wang, C and He, Q and Halim, U and Liu, Y and Zhu, E and Lin, Z and Xiao, H and Duan, X and Feng, Z and Cheng, R and Weiss, NO and Ye, G and Huang, YC and Wu, H and Cheng, HC and Shakir, I and Liao, L and Chen, X and Goddard, WA and Huang, Y and Duan, X}, title = {Monolayer atomic crystal molecular superlattices.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {231-236}, pmid = {29517002}, issn = {1476-4687}, abstract = {Artificial superlattices, based on van der Waals heterostructures of two-dimensional atomic crystals such as graphene or molybdenum disulfide, offer technological opportunities beyond the reach of existing materials. Typical strategies for creating such artificial superlattices rely on arduous layer-by-layer exfoliation and restacking, with limited yield and reproducibility. The bottom-up approach of using chemical-vapour deposition produces high-quality heterostructures but becomes increasingly difficult for high-order superlattices. The intercalation of selected two-dimensional atomic crystals with alkali metal ions offers an alternative way to superlattice structures, but these usually have poor stability and seriously altered electronic properties. Here we report an electrochemical molecular intercalation approach to a new class of stable superlattices in which monolayer atomic crystals alternate with molecular layers. Using black phosphorus as a model system, we show that intercalation with cetyl-trimethylammonium bromide produces monolayer phosphorene molecular superlattices in which the interlayer distance is more than double that in black phosphorus, effectively isolating the phosphorene monolayers. Electrical transport studies of transistors fabricated from the monolayer phosphorene molecular superlattice show an on/off current ratio exceeding 107, along with excellent mobility and superior stability. We further show that several different two-dimensional atomic crystals, such as molybdenum disulfide and tungsten diselenide, can be intercalated with quaternary ammonium molecules of varying sizes and symmetries to produce a broad class of superlattices with tailored molecular structures, interlayer distances, phase compositions, electronic and optical properties. These studies define a versatile material platform for fundamental studies and potential technological applications.}, } @article {pmid29517001, year = {2018}, author = {Iess, L and Folkner, WM and Durante, D and Parisi, M and Kaspi, Y and Galanti, E and Guillot, T and Hubbard, WB and Stevenson, DJ and Anderson, JD and Buccino, DR and Casajus, LG and Milani, A and Park, R and Racioppa, P and Serra, D and Tortora, P and Zannoni, M and Cao, H and Helled, R and Lunine, JI and Miguel, Y and Militzer, B and Wahl, S and Connerney, JEP and Levin, SM and Bolton, SJ}, title = {Measurement of Jupiter's asymmetric gravity field.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {220-222}, pmid = {29517001}, issn = {1476-4687}, abstract = {The gravity harmonics of a fluid, rotating planet can be decomposed into static components arising from solid-body rotation and dynamic components arising from flows. In the absence of internal dynamics, the gravity field is axially and hemispherically symmetric and is dominated by even zonal gravity harmonics J2n that are approximately proportional to qn, where q is the ratio between centrifugal acceleration and gravity at the planet's equator. Any asymmetry in the gravity field is attributed to differential rotation and deep atmospheric flows. The odd harmonics, J3, J5, J7, J9 and higher, are a measure of the depth of the winds in the different zones of the atmosphere. Here we report measurements of Jupiter's gravity harmonics (both even and odd) through precise Doppler tracking of the Juno spacecraft in its polar orbit around Jupiter. We find a north-south asymmetry, which is a signature of atmospheric and interior flows. Analysis of the harmonics, described in two accompanying papers, provides the vertical profile of the winds and precise constraints for the depth of Jupiter's dynamical atmosphere.}, } @article {pmid29517000, year = {2018}, author = {Guillot, T and Miguel, Y and Militzer, B and Hubbard, WB and Kaspi, Y and Galanti, E and Cao, H and Helled, R and Wahl, SM and Iess, L and Folkner, WM and Stevenson, DJ and Lunine, JI and Reese, DR and Biekman, A and Parisi, M and Durante, D and Connerney, JEP and Levin, SM and Bolton, SJ}, title = {A suppression of differential rotation in Jupiter's deep interior.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {227-230}, pmid = {29517000}, issn = {1476-4687}, abstract = {Jupiter's atmosphere is rotating differentially, with zones and belts rotating at speeds that differ by up to 100 metres per second. Whether this is also true of the gas giant's interior has been unknown, limiting our ability to probe the structure and composition of the planet. The discovery by the Juno spacecraft that Jupiter's gravity field is north-south asymmetric and the determination of its non-zero odd gravitational harmonics J3, J5, J7 and J9 demonstrates that the observed zonal cloud flow must persist to a depth of about 3,000 kilometres from the cloud tops. Here we report an analysis of Jupiter's even gravitational harmonics J4, J6, J8 and J10 as observed by Juno and compared to the predictions of interior models. We find that the deep interior of the planet rotates nearly as a rigid body, with differential rotation decreasing by at least an order of magnitude compared to the atmosphere. Moreover, we find that the atmospheric zonal flow extends to more than 2,000 kilometres and to less than 3,500 kilometres, making it fully consistent with the constraints obtained independently from the odd gravitational harmonics. This depth corresponds to the point at which the electric conductivity becomes large and magnetic drag should suppress differential rotation. Given that electric conductivity is dependent on planetary mass, we expect the outer, differentially rotating region to be at least three times deeper in Saturn and to be shallower in massive giant planets and brown dwarfs.}, } @article {pmid29516999, year = {2018}, author = {Santos, FP and Santos, FC and Pacheco, JM}, title = {Social norm complexity and past reputations in the evolution of cooperation.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {242-245}, pmid = {29516999}, issn = {1476-4687}, mesh = {Altruism ; *Biological Evolution ; *Cooperative Behavior ; Humans ; Models, Psychological ; Morals ; *Social Norms ; }, abstract = {Indirect reciprocity is the most elaborate and cognitively demanding of all known cooperation mechanisms, and is the most specifically human because it involves reputation and status. By helping someone, individuals may increase their reputation, which may change the predisposition of others to help them in future. The revision of an individual's reputation depends on the social norms that establish what characterizes a good or bad action and thus provide a basis for morality. Norms based on indirect reciprocity are often sufficiently complex that an individual's ability to follow subjective rules becomes important, even in models that disregard the past reputations of individuals, and reduce reputations to either 'good' or 'bad' and actions to binary decisions. Here we include past reputations in such a model and identify the key pattern in the associated norms that promotes cooperation. Of the norms that comply with this pattern, the one that leads to maximal cooperation (greater than 90 per cent) with minimum complexity does not discriminate on the basis of past reputation; the relative performance of this norm is particularly evident when we consider a 'complexity cost' in the decision process. This combination of high cooperation and low complexity suggests that simple moral principles can elicit cooperation even in complex environments.}, } @article {pmid29516998, year = {2018}, author = {Nestola, F and Korolev, N and Kopylova, M and Rotiroti, N and Pearson, DG and Pamato, MG and Alvaro, M and Peruzzo, L and Gurney, JJ and Moore, AE and Davidson, J}, title = {CaSiO3 perovskite in diamond indicates the recycling of oceanic crust into the lower mantle.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {237-241}, pmid = {29516998}, issn = {1476-4687}, abstract = {Laboratory experiments and seismology data have created a clear theoretical picture of the most abundant minerals that comprise the deeper parts of the Earth's mantle. Discoveries of some of these minerals in 'super-deep' diamonds-formed between two hundred and about one thousand kilometres into the lower mantle-have confirmed part of this picture. A notable exception is the high-pressure perovskite-structured polymorph of calcium silicate (CaSiO3). This mineral-expected to be the fourth most abundant in the Earth-has not previously been found in nature. Being the dominant host for calcium and, owing to its accommodating crystal structure, the major sink for heat-producing elements (potassium, uranium and thorium) in the transition zone and lower mantle, it is critical to establish its presence. Here we report the discovery of the perovskite-structured polymorph of CaSiO3 in a diamond from South African Cullinan kimberlite. The mineral is intergrown with about six per cent calcium titanate (CaTiO3). The titanium-rich composition of this inclusion indicates a bulk composition consistent with derivation from basaltic oceanic crust subducted to pressures equivalent to those present at the depths of the uppermost lower mantle. The relatively 'heavy' carbon isotopic composition of the surrounding diamond, together with the pristine high-pressure CaSiO3 structure, provides evidence for the recycling of oceanic crust and surficial carbon to lower-mantle depths.}, } @article {pmid29516997, year = {2018}, author = {Adriani, A and Mura, A and Orton, G and Hansen, C and Altieri, F and Moriconi, ML and Rogers, J and Eichstädt, G and Momary, T and Ingersoll, AP and Filacchione, G and Sindoni, G and Tabataba-Vakili, F and Dinelli, BM and Fabiano, F and Bolton, SJ and Connerney, JEP and Atreya, SK and Lunine, JI and Tosi, F and Migliorini, A and Grassi, D and Piccioni, G and Noschese, R and Cicchetti, A and Plainaki, C and Olivieri, A and O'Neill, ME and Turrini, D and Stefani, S and Sordini, R and Amoroso, M}, title = {Clusters of cyclones encircling Jupiter's poles.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {216-219}, pmid = {29516997}, issn = {1476-4687}, abstract = {The familiar axisymmetric zones and belts that characterize Jupiter's weather system at lower latitudes give way to pervasive cyclonic activity at higher latitudes. Two-dimensional turbulence in combination with the Coriolis β-effect (that is, the large meridionally varying Coriolis force on the giant planets of the Solar System) produces alternating zonal flows. The zonal flows weaken with rising latitude so that a transition between equatorial jets and polar turbulence on Jupiter can occur. Simulations with shallow-water models of giant planets support this transition by producing both alternating flows near the equator and circumpolar cyclones near the poles. Jovian polar regions are not visible from Earth owing to Jupiter's low axial tilt, and were poorly characterized by previous missions because the trajectories of these missions did not venture far from Jupiter's equatorial plane. Here we report that visible and infrared images obtained from above each pole by the Juno spacecraft during its first five orbits reveal persistent polygonal patterns of large cyclones. In the north, eight circumpolar cyclones are observed about a single polar cyclone; in the south, one polar cyclone is encircled by five circumpolar cyclones. Cyclonic circulation is established via time-lapse imagery obtained over intervals ranging from 20 minutes to 4 hours. Although migration of cyclones towards the pole might be expected as a consequence of the Coriolis β-effect, by which cyclonic vortices naturally drift towards the rotational pole, the configuration of the cyclones is without precedent on other planets (including Saturn's polar hexagonal features). The manner in which the cyclones persist without merging and the process by which they evolve to their current configuration are unknown.}, } @article {pmid29516996, year = {2018}, author = {Yan, R and Khalsa, G and Vishwanath, S and Han, Y and Wright, J and Rouvimov, S and Katzer, DS and Nepal, N and Downey, BP and Muller, DA and Xing, HG and Meyer, DJ and Jena, D}, title = {GaN/NbN epitaxial semiconductor/superconductor heterostructures.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {183-189}, pmid = {29516996}, issn = {1476-4687}, abstract = {Epitaxy is a process by which a thin layer of one crystal is deposited in an ordered fashion onto a substrate crystal. The direct epitaxial growth of semiconductor heterostructures on top of crystalline superconductors has proved challenging. Here, however, we report the successful use of molecular beam epitaxy to grow and integrate niobium nitride (NbN)-based superconductors with the wide-bandgap family of semiconductors-silicon carbide, gallium nitride (GaN) and aluminium gallium nitride (AlGaN). We apply molecular beam epitaxy to grow an AlGaN/GaN quantum-well heterostructure directly on top of an ultrathin crystalline NbN superconductor. The resulting high-mobility, two-dimensional electron gas in the semiconductor exhibits quantum oscillations, and thus enables a semiconductor transistor-an electronic gain element-to be grown and fabricated directly on a crystalline superconductor. Using the epitaxial superconductor as the source load of the transistor, we observe in the transistor output characteristics a negative differential resistance-a feature often used in amplifiers and oscillators. Our demonstration of the direct epitaxial growth of high-quality semiconductor heterostructures and devices on crystalline nitride superconductors opens up the possibility of combining the macroscopic quantum effects of superconductors with the electronic, photonic and piezoelectric properties of the group III/nitride semiconductor family.}, } @article {pmid29516995, year = {2018}, author = {Kaspi, Y and Galanti, E and Hubbard, WB and Stevenson, DJ and Bolton, SJ and Iess, L and Guillot, T and Bloxham, J and Connerney, JEP and Cao, H and Durante, D and Folkner, WM and Helled, R and Ingersoll, AP and Levin, SM and Lunine, JI and Miguel, Y and Militzer, B and Parisi, M and Wahl, SM}, title = {Jupiter's atmospheric jet streams extend thousands of kilometres deep.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {223-226}, pmid = {29516995}, issn = {1476-4687}, abstract = {The depth to which Jupiter's observed east-west jet streams extend has been a long-standing question. Resolving this puzzle has been a primary goal for the Juno spacecraft, which has been in orbit around the gas giant since July 2016. Juno's gravitational measurements have revealed that Jupiter's gravitational field is north-south asymmetric, which is a signature of the planet's atmospheric and interior flows. Here we report that the measured odd gravitational harmonics J3, J5, J7 and J9 indicate that the observed jet streams, as they appear at the cloud level, extend down to depths of thousands of kilometres beneath the cloud level, probably to the region of magnetic dissipation at a depth of about 3,000 kilometres. By inverting the measured gravity values into a wind field, we calculate the most likely vertical profile of the deep atmospheric and interior flow, and the latitudinal dependence of its depth. Furthermore, the even gravity harmonics J8 and J10 resulting from this flow profile also match the measurements, when taking into account the contribution of the interior structure. These results indicate that the mass of the dynamical atmosphere is about one per cent of Jupiter's total mass.}, } @article {pmid29516180, year = {2018}, author = {Nascimento, FX and Tavares, MJ and Glick, BR and Rossi, MJ}, title = {Improvement of Cupriavidus taiwanensis Nodulation and Plant Growth Promoting Abilities by the Expression of an Exogenous ACC Deaminase Gene.}, journal = {Current microbiology}, volume = {75}, number = {8}, pages = {961-965}, pmid = {29516180}, issn = {1432-0991}, mesh = {Carbon-Carbon Lyases/*genetics/metabolism ; Cupriavidus/*genetics/*metabolism ; Gene Transfer Techniques ; Mimosa/*growth & development/*microbiology ; Plant Root Nodulation/*genetics ; Plasmids/genetics ; Transformation, Genetic/genetics ; }, abstract = {Several rhizobial strains possess the ability to modulate leguminous plants ethylene levels by producing the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase. While the effect of ACC deaminase has been studied in several rhizobia belonging to the Alphaproteobacteria class, not much is understood about its impact in the nodulation abilities of rhizobia belonging to the Betaproteobacteria class, which are common symbionts of Mimosa species. In this work, we report the impact of ACC deaminase production by the Betaproteobacterium, Cupriavidus taiwanensis STM894, and its role in the nodulation of Mimosa pudica. C. taiwanensis STM894 was studied following its transformation with the plasmid pRKACC, containing an ACC deaminase gene. The expression of the exogenous ACC deaminase led to increased nodulation and M. pudica growth promotion by C. taiwanensis STM894. These results indicate that ACC deaminase plays an important role in modulating ethylene levels that inhibit the nodulation process induced by both rhizobia belonging to the Alpha and Betaproteobacteria class.}, } @article {pmid29514960, year = {2018}, author = {Mitchell, S and Roy, K and Zangle, TA and Hoffmann, A}, title = {Nongenetic origins of cell-to-cell variability in B lymphocyte proliferation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2888-E2897}, pmid = {29514960}, issn = {1091-6490}, support = {R01 AI132731/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; B-Lymphocytes/*cytology/drug effects/physiology ; Cell Lineage ; Cell Proliferation/drug effects ; Female ; Mice, Inbred C57BL ; Mice, Transgenic ; *Models, Biological ; Oligopeptides/pharmacology ; Proto-Oncogene Proteins c-bcr/genetics ; Single-Cell Analysis/methods ; Stochastic Processes ; Time-Lapse Imaging ; Workflow ; }, abstract = {Rapid antibody production in response to invading pathogens requires the dramatic expansion of pathogen-derived antigen-specific B lymphocyte populations. Whether B cell population dynamics are based on stochastic competition between competing cell fates, as in the development of competence by the bacterium Bacillus subtilis, or on deterministic cell fate decisions that execute a predictable program, as during the development of the worm Caenorhabditis elegans, remains unclear. Here, we developed long-term live-cell microscopy of B cell population expansion and multiscale mechanistic computational modeling to characterize the role of molecular noise in determining phenotype heterogeneity. We show that the cell lineage trees underlying B cell population dynamics are mediated by a largely predictable decision-making process where the heterogeneity of cell proliferation and death decisions at any given timepoint largely derives from nongenetic heterogeneity in the founder cells. This means that contrary to previous models, only a minority of genetically identical founder cells contribute the majority to the population response. We computationally predict and experimentally confirm nongenetic molecular determinants that are predictive of founder cells' proliferative capacity. While founder cell heterogeneity may arise from different exposure histories, we show that it may also be due to the gradual accumulation of small amounts of intrinsic noise during the lineage differentiation process of hematopoietic stem cells to mature B cells. Our finding of the largely deterministic nature of B lymphocyte responses may provide opportunities for diagnostic and therapeutic development.}, } @article {pmid29514959, year = {2018}, author = {Maher, MJ and Herath, AS and Udagedara, SR and Dougan, DA and Truscott, KN}, title = {Crystal structure of bacterial succinate:quinone oxidoreductase flavoprotein SdhA in complex with its assembly factor SdhE.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2982-2987}, pmid = {29514959}, issn = {1091-6490}, mesh = {Bacterial Proteins ; Crystallization ; Crystallography, X-Ray ; Electron Transport Complex II/genetics/*metabolism ; Escherichia coli ; Escherichia coli Proteins/*chemistry/ultrastructure ; Flavoproteins/*chemistry/ultrastructure ; Models, Molecular ; Protein Binding ; Protein Conformation ; Protein Domains ; Strobilurins ; }, abstract = {Succinate:quinone oxidoreductase (SQR) functions in energy metabolism, coupling the tricarboxylic acid cycle and electron transport chain in bacteria and mitochondria. The biogenesis of flavinylated SdhA, the catalytic subunit of SQR, is assisted by a highly conserved assembly factor termed SdhE in bacteria via an unknown mechanism. By using X-ray crystallography, we have solved the structure of Escherichia coli SdhE in complex with SdhA to 2.15-Å resolution. Our structure shows that SdhE makes a direct interaction with the flavin adenine dinucleotide-linked residue His45 in SdhA and maintains the capping domain of SdhA in an "open" conformation. This displaces the catalytic residues of the succinate dehydrogenase active site by as much as 9.0 Å compared with SdhA in the assembled SQR complex. These data suggest that bacterial SdhE proteins, and their mitochondrial homologs, are assembly chaperones that constrain the conformation of SdhA to facilitate efficient flavinylation while regulating succinate dehydrogenase activity for productive biogenesis of SQR.}, } @article {pmid29514958, year = {2018}, author = {Tenaillon, O}, title = {Experimental evolution heals the scars of genome-scale recoding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2853-2855}, pmid = {29514958}, issn = {1091-6490}, mesh = {*Cicatrix ; *Genome ; Humans ; Wound Healing ; }, } @article {pmid29514957, year = {2018}, author = {Costa-Pereira, R and Lucas, C and Crossa, M and Anderson, JT and Albuquerque, BW and Dary, EP and Piedade, MTF and Demarchi, LO and Rebouças, ER and Costa, GDS and Galetti, M and Correa, SB}, title = {Defaunation shadow on mutualistic interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2673-E2675}, pmid = {29514957}, issn = {1091-6490}, mesh = {Animals ; *Rumen ; *Symbiosis ; }, } @article {pmid29514956, year = {2018}, author = {Ning, Y and Wang, GL}, title = {Breeding plant broad-spectrum resistance without yield penalties.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2859-2861}, pmid = {29514956}, issn = {1091-6490}, mesh = {*Breeding ; Disease Resistance/*genetics ; Genes, Plant ; Humans ; Plant Diseases ; }, } @article {pmid29514955, year = {2018}, author = {Purayil, HT and Daaka, Y}, title = {β-Arrestin1 mediates hMENA expression and ovarian cancer metastasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2856-2858}, pmid = {29514955}, issn = {1091-6490}, mesh = {Female ; Humans ; *Ovarian Neoplasms ; *beta-Arrestins ; }, } @article {pmid29514954, year = {2018}, author = {Song, J and Pfanner, N and Becker, T}, title = {Assembling the mitochondrial ATP synthase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2850-2852}, pmid = {29514954}, issn = {1091-6490}, mesh = {Adenosine Triphosphate ; *Mitochondria ; *Mitochondrial Proton-Translocating ATPases ; }, } @article {pmid29514691, year = {2018}, author = {Yurkovich, JT and Bordbar, A and Sigurjónsson, ÓE and Palsson, BO}, title = {Systems biology as an emerging paradigm in transfusion medicine.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {31}, pmid = {29514691}, issn = {1752-0509}, support = {R43 HL123074/HL/NHLBI NIH HHS/United States ; ERC 232816//European Research Council/International ; NHLBI R43HL123074//National Heart, Lung, and Blood Institute/ ; }, abstract = {Blood transfusions are an important part of modern medicine, delivering approximately 85 million blood units to patients annually. Recently, the field of transfusion medicine has started to benefit from the "omic" data revolution and corresponding systems biology analytics. The red blood cell is the simplest human cell, making it an accessible starting point for the application of systems biology approaches.In this review, we discuss how the use of systems biology has led to significant contributions in transfusion medicine, including the identification of three distinct metabolic states that define the baseline decay process of red blood cells during storage. We then describe how a series of perturbations to the standard storage conditions characterized the underlying metabolic phenotypes. Finally, we show how the analysis of high-dimensional data led to the identification of predictive biomarkers.The transfusion medicine community is in the early stages of a paradigm shift, moving away from the measurement of a handful of chosen variables to embracing systems biology and a cell-scale point of view.}, } @article {pmid29514634, year = {2018}, author = {Desert, C and Baéza, E and Aite, M and Boutin, M and Le Cam, A and Montfort, J and Houee-Bigot, M and Blum, Y and Roux, PF and Hennequet-Antier, C and Berri, C and Metayer-Coustard, S and Collin, A and Allais, S and Le Bihan, E and Causeur, D and Gondret, F and Duclos, MJ and Lagarrigue, S}, title = {Multi-tissue transcriptomic study reveals the main role of liver in the chicken adaptive response to a switch in dietary energy source through the transcriptional regulation of lipogenesis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {187}, pmid = {29514634}, issn = {1471-2164}, mesh = {Animals ; Chickens ; Diet, High-Fat/*veterinary ; Dietary Fiber/*administration & dosage ; Gene Expression Regulation ; *Lipogenesis ; Liver/drug effects/*metabolism ; Meat ; Starch/*administration & dosage ; Transcription, Genetic ; Transcriptome ; }, abstract = {BACKGROUND: Because the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues - liver, adipose tissue and muscle - as well as in circulating blood cells.

RESULTS: We revealed the fine-tuned regulation of many hepatic genes encoding key enzymes driving glycogenesis and de novo fatty acid synthesis pathways and of some genes participating in oxidation. Among the genes expressed upon consumption of a high-fat, high-fiber diet, we highlighted CPT1A, which encodes a key enzyme in the regulation of fatty acid oxidation. Conversely, the repression of lipogenic genes by the high-fat diet was clearly associated with the down-regulation of SREBF1 transcripts but was not associated with the transcript regulation of MLXIPL and NR1H3, which are both transcription factors. This result suggests a pivotal role for SREBF1 in lipogenesis regulation in response to a decrease in dietary starch and an increase in dietary PUFA. Other prospective regulators of de novo hepatic lipogenesis were suggested, such as PPARD, JUN, TADA2A and KAT2B, the last two genes belonging to the lysine acetyl transferase (KAT) complex family regulating histone and non-histone protein acetylation. Hepatic glycogenic genes were also down-regulated in chickens fed a high-fat, high-fiber diet compared to those in chickens fed a starch-based diet. No significant dietary-associated variations in gene expression profiles was observed in the other studied tissues, suggesting that the liver mainly contributed to the adaptation of birds to changes in energy source and nutrients in their diets, at least at the transcriptional level. Moreover, we showed that PUFA deposition observed in the different tissues may not rely on transcriptional changes.

CONCLUSION: We showed the major role of the liver, at the gene expression level, in the adaptive response of chicken to dietary starch substitution with fat and fiber.}, } @article {pmid29514626, year = {2018}, author = {Jenkinson, G and Abante, J and Feinberg, AP and Goutsias, J}, title = {An information-theoretic approach to the modeling and analysis of whole-genome bisulfite sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {87}, pmid = {29514626}, issn = {1471-2105}, support = {CCF-1656201//Division of Computing and Communication Foundations/International ; HG008529/NH/NIH HHS/United States ; CA054358/NH/NIH HHS/United States ; }, mesh = {Base Sequence ; Computer Simulation ; CpG Islands/genetics ; DNA Methylation/genetics ; Entropy ; Epigenesis, Genetic ; Gene Ontology ; Genome, Human ; Humans ; *Information Theory ; Lung Neoplasms/genetics ; *Models, Theoretical ; Probability ; *Statistics as Topic ; Sulfites/*chemistry ; Web Browser ; Whole Genome Sequencing/*methods ; }, abstract = {BACKGROUND: DNA methylation is a stable form of epigenetic memory used by cells to control gene expression. Whole genome bisulfite sequencing (WGBS) has emerged as a gold-standard experimental technique for studying DNA methylation by producing high resolution genome-wide methylation profiles. Statistical modeling and analysis is employed to computationally extract and quantify information from these profiles in an effort to identify regions of the genome that demonstrate crucial or aberrant epigenetic behavior. However, the performance of most currently available methods for methylation analysis is hampered by their inability to directly account for statistical dependencies between neighboring methylation sites, thus ignoring significant information available in WGBS reads.

RESULTS: We present a powerful information-theoretic approach for genome-wide modeling and analysis of WGBS data based on the 1D Ising model of statistical physics. This approach takes into account correlations in methylation by utilizing a joint probability model that encapsulates all information available in WGBS methylation reads and produces accurate results even when applied on single WGBS samples with low coverage. Using the Shannon entropy, our approach provides a rigorous quantification of methylation stochasticity in individual WGBS samples genome-wide. Furthermore, it utilizes the Jensen-Shannon distance to evaluate differences in methylation distributions between a test and a reference sample. Differential performance assessment using simulated and real human lung normal/cancer data demonstrate a clear superiority of our approach over DSS, a recently proposed method for WGBS data analysis. Critically, these results demonstrate that marginal methods become statistically invalid when correlations are present in the data.

CONCLUSIONS: This contribution demonstrates clear benefits and the necessity of modeling joint probability distributions of methylation using the 1D Ising model of statistical physics and of quantifying methylation stochasticity using concepts from information theory. By employing this methodology, substantial improvement of DNA methylation analysis can be achieved by effectively taking into account the massive amount of statistical information available in WGBS data, which is largely ignored by existing methods.}, } @article {pmid29514601, year = {2018}, author = {Zou, B and Lee, VHF and Yan, H}, title = {Prediction of sensitivity to gefitinib/erlotinib for EGFR mutations in NSCLC based on structural interaction fingerprints and multilinear principal component analysis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {88}, pmid = {29514601}, issn = {1471-2105}, support = {Projects C1007-15G and 11200715//Hong Kong Research Grants Council/International ; Project 7004862//City University of Hong Kong/International ; }, mesh = {Carcinoma, Non-Small-Cell Lung/*drug therapy/*genetics ; Computer Simulation ; ErbB Receptors/*genetics ; Erlotinib Hydrochloride/*therapeutic use ; Exons/genetics ; Gefitinib ; Humans ; Lung Neoplasms/drug therapy/*genetics ; Mutation/*genetics ; *Principal Component Analysis ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Quinazolines/*therapeutic use ; }, abstract = {BACKGROUND: Non-small cell lung cancer (NSCLC) with activating EGFR mutations, especially exon 19 deletions and the L858R point mutation, is particularly responsive to gefitinib and erlotinib. However, the sensitivity varies for less common and rare EGFR mutations. There are various explanations for the low sensitivity of EGFR exon 20 insertions and the exon 20 T790 M point mutation to gefitinib/erlotinib. However, few studies discuss, from a structural perspective, why less common mutations, like G719X and L861Q, have moderate sensitivity to gefitinib/erlotinib.

RESULTS: To decode the drug sensitivity/selectivity of EGFR mutants, it is important to analyze the interaction between EGFR mutants and EGFR inhibitors. In this paper, the 30 most common EGFR mutants were selected and the technique of protein-ligand interaction fingerprint (IFP) was applied to analyze and compare the binding modes of EGFR mutant-gefitinib/erlotinib complexes. Molecular dynamics simulations were employed to obtain the dynamic trajectory and a matrix of IFPs for each EGFR mutant-inhibitor complex. Multilinear Principal Component Analysis (MPCA) was applied for dimensionality reduction and feature selection. The selected features were further analyzed for use as a drug sensitivity predictor. The results showed that the accuracy of prediction of drug sensitivity was very high for both gefitinib and erlotinib. Targeted Projection Pursuit (TPP) was used to show that the data points can be easily separated based on their sensitivities to gefetinib/erlotinib.

CONCLUSIONS: We can conclude that the IFP features of EGFR mutant-TKI complexes and the MPCA-based tensor object feature extraction are useful to predict the drug sensitivity of EGFR mutants. The findings provide new insights for studying and predicting drug resistance/sensitivity of EGFR mutations in NSCLC and can be beneficial to the design of future targeted therapies and innovative drug discovery.}, } @article {pmid29514313, year = {2018}, author = {Phuong, MA and Mahardika, GN}, title = {Targeted Sequencing of Venom Genes from Cone Snail Genomes Improves Understanding of Conotoxin Molecular Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1210-1224}, pmid = {29514313}, issn = {1537-1719}, support = {S10 RR027303/RR/NCRR NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; }, abstract = {To expand our capacity to discover venom sequences from the genomes of venomous organisms, we applied targeted sequencing techniques to selectively recover venom gene superfamilies and nontoxin loci from the genomes of 32 cone snail species (family, Conidae), a diverse group of marine gastropods that capture their prey using a cocktail of neurotoxic peptides (conotoxins). We were able to successfully recover conotoxin gene superfamilies across all species with high confidence (> 100× coverage) and used these data to provide new insights into conotoxin evolution. First, we found that conotoxin gene superfamilies are composed of one to six exons and are typically short in length (mean = ∼85 bp). Second, we expanded our understanding of the following genetic features of conotoxin evolution: 1) positive selection, where exons coding the mature toxin region were often three times more divergent than their adjacent noncoding regions, 2) expression regulation, with comparisons to transcriptome data showing that cone snails only express a fraction of the genes available in their genome (24-63%), and 3) extensive gene turnover, where Conidae species varied from 120 to 859 conotoxin gene copies. Finally, using comparative phylogenetic methods, we found that while diet specificity did not predict patterns of conotoxin evolution, dietary breadth was positively correlated with total conotoxin gene diversity. Overall, the targeted sequencing technique demonstrated here has the potential to radically increase the pace at which venom gene families are sequenced and studied, reshaping our ability to understand the impact of genetic changes on ecologically relevant phenotypes and subsequent diversification.}, } @article {pmid29514253, year = {2018}, author = {Rippin, M and Lange, S and Sausen, N and Becker, B}, title = {Biodiversity of biological soil crusts from the Polar Regions revealed by metabarcoding.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy036}, pmid = {29514253}, issn = {1574-6941}, abstract = {Biological soil crusts (BSCs) are amalgamations of autotrophic, heterotrophic and saprotrophic organisms. In the Polar Regions, these unique communities occupy essential ecological functions such as primary production, nitrogen fixation and ecosystem engineering. Here, we present the first molecular survey of BSCs from the Arctic and Antarctica focused on both eukaryotes and prokaryotes as well as passive and active biodiversity. Considering sequence abundance, Bryophyta is among the most abundant taxa in all analyzed BSCs suggesting that they were in a late successional stage. In terms of algal and cyanobacterial biodiversity, the genera Chloromonas, Coccomyxa, Elliptochloris and Nostoc were identified in all samples regardless of origin confirming their ubiquitous distribution. For the first time, we found the chrysophyte Spumella to be common in polar BSCs as it was present in all analyzed samples. Co-occurrence analysis revealed the presence of sulfur metabolizing microbes indicating that BSCs also play an important role for the sulfur cycle. In general, phototrophs were most abundant within the BSCs but there was also a diverse community of heterotrophs and saprotrophs. Our results show that BSCs are unique microecosystems in polar environments with an unexpectedly high biodiversity.}, } @article {pmid29514229, year = {2018}, author = {Hultman, J and Tamminen, M and Pärnänen, K and Cairns, J and Karkman, A and Virta, M}, title = {Host range of antibiotic resistance genes in wastewater treatment plant influent and effluent.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, pmid = {29514229}, issn = {1574-6941}, abstract = {Wastewater treatment plants (WWTPs) collect wastewater from various sources for a multi-step treatment process. By mixing a large variety of bacteria and promoting their proximity, WWTPs constitute potential hotspots for the emergence of antibiotic resistant bacteria. Concerns have been expressed regarding the potential of WWTPs to spread antibiotic resistance genes (ARGs) from environmental reservoirs to human pathogens. We utilized epicPCR (Emulsion, Paired Isolation and Concatenation PCR) to detect the bacterial hosts of ARGs in two WWTPs. We identified the host distribution of four resistance-associated genes (tetM, int1, qacEΔ1and blaOXA-58) in influent and effluent. The bacterial hosts of these resistance genes varied between the WWTP influent and effluent, with a generally decreasing host range in the effluent. Through 16S rRNA gene sequencing, it was determined that the resistance gene carrying bacteria include both abundant and rare taxa. Our results suggest that the studied WWTPs mostly succeed in decreasing the host range of the resistance genes during the treatment process. Still, there were instances where effluent contained resistance genes in bacterial groups not carrying these genes in the influent. By permitting exhaustive profiling of resistance-associated gene hosts in WWTP bacterial communities, the application of epicPCR provides a new level of precision to our resistance gene risk estimates.}, } @article {pmid29513657, year = {2018}, author = {Hill, PWS and Leitch, HG and Requena, CE and Sun, Z and Amouroux, R and Roman-Trufero, M and Borkowska, M and Terragni, J and Vaisvila, R and Linnett, S and Bagci, H and Dharmalingham, G and Haberle, V and Lenhard, B and Zheng, Y and Pradhan, S and Hajkova, P}, title = {Epigenetic reprogramming enables the transition from primordial germ cell to gonocyte.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {392-396}, pmid = {29513657}, issn = {1476-4687}, support = {MC_U120092689//Medical Research Council/United Kingdom ; MC_UP_1102/1//Medical Research Council/United Kingdom ; R44 GM096723/GM/NIGMS NIH HHS/United States ; }, mesh = {5-Methylcytosine/analogs & derivatives/metabolism ; Animals ; Cellular Reprogramming/*genetics ; DNA Methylation ; DNA-Binding Proteins/genetics/metabolism ; *Epigenesis, Genetic ; Female ; Gametogenesis/*genetics ; Germ Cells/*cytology/*metabolism ; Male ; Meiosis ; Mice ; Proto-Oncogene Proteins/genetics/metabolism ; }, abstract = {Gametes are highly specialized cells that can give rise to the next generation through their ability to generate a totipotent zygote. In mice, germ cells are first specified in the developing embryo around embryonic day (E) 6.25 as primordial germ cells (PGCs). Following subsequent migration into the developing gonad, PGCs undergo a wave of extensive epigenetic reprogramming around E10.5-E11.5, including genome-wide loss of 5-methylcytosine. The underlying molecular mechanisms of this process have remained unclear, leading to our inability to recapitulate this step of germline development in vitro. Here we show, using an integrative approach, that this complex reprogramming process involves coordinated interplay among promoter sequence characteristics, DNA (de)methylation, the polycomb (PRC1) complex and both DNA demethylation-dependent and -independent functions of TET1 to enable the activation of a critical set of germline reprogramming-responsive genes involved in gamete generation and meiosis. Our results also reveal an unexpected role for TET1 in maintaining but not driving DNA demethylation in gonadal PGCs. Collectively, our work uncovers a fundamental biological role for gonadal germline reprogramming and identifies the epigenetic principles of the PGC-to-gonocyte transition that will help to guide attempts to recapitulate complete gametogenesis in vitro.}, } @article {pmid29513656, year = {2018}, author = {Turner, BL and Brenes-Arguedas, T and Condit, R}, title = {Pervasive phosphorus limitation of tree species but not communities in tropical forests.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {367-370}, pmid = {29513656}, issn = {1476-4687}, support = {CA21765/CA/NCI NIH HHS/United States ; }, mesh = {Climate Change ; *Forests ; Humidity ; Panama ; Phosphates/metabolism ; Phosphorus/*metabolism ; Resins, Plant/metabolism ; Soil/chemistry ; Species Specificity ; Trees/classification/*growth & development/*metabolism ; *Tropical Climate ; Water/metabolism ; }, abstract = {Phosphorus availability is widely assumed to limit primary productivity in tropical forests, but support for this paradigm is equivocal. Although biogeochemical theory predicts that phosphorus limitation should be prevalent on old, strongly weathered soils, experimental manipulations have failed to detect a consistent response to phosphorus addition in species-rich lowland tropical forests. Here we show, by quantifying the growth of 541 tropical tree species across a steep natural phosphorus gradient in Panama, that phosphorus limitation is widespread at the level of individual species and strengthens markedly below a threshold of two parts per million exchangeable soil phosphate. However, this pervasive species-specific phosphorus limitation does not translate into a community-wide response, because some species grow rapidly on infertile soils despite extremely low phosphorus availability. These results redefine our understanding of nutrient limitation in diverse plant communities and have important implications for attempts to predict the response of tropical forests to environmental change.}, } @article {pmid29513655, year = {2018}, author = {Kennedy, P and Higginson, AD and Radford, AN and Sumner, S}, title = {Altruism in a volatile world.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {359-362}, pmid = {29513655}, issn = {1476-4687}, support = {682253//European Research Council/International ; }, mesh = {*Altruism ; Animals ; *Biological Evolution ; Genetic Fitness ; Genotype ; Models, Biological ; Reproduction/genetics/physiology ; Selection, Genetic ; Stochastic Processes ; }, abstract = {The evolution of altruism-costly self-sacrifice in the service of others-has puzzled biologists since The Origin of Species. For half a century, attempts to understand altruism have developed around the concept that altruists may help relatives to have extra offspring in order to spread shared genes. This theory-known as inclusive fitness-is founded on a simple inequality termed Hamilton's rule. However, explanations of altruism have typically not considered the stochasticity of natural environments, which will not necessarily favour genotypes that produce the greatest average reproductive success. Moreover, empirical data across many taxa reveal associations between altruism and environmental stochasticity, a pattern not predicted by standard interpretations of Hamilton's rule. Here we derive Hamilton's rule with explicit stochasticity, leading to new predictions about the evolution of altruism. We show that altruists can increase the long-term success of their genotype by reducing the temporal variability in the number of offspring produced by their relatives. Consequently, costly altruism can evolve even if it has a net negative effect on the average reproductive success of related recipients. The selective pressure on volatility-suppressing altruism is proportional to the coefficient of variation in population fitness, and is therefore diminished by its own success. Our results formalize the hitherto elusive link between bet-hedging and altruism, and reveal missing fitness effects in the evolution of animal societies.}, } @article {pmid29513654, year = {2018}, author = {Cui, Z and Zhang, H and Chen, X and Zhang, C and Ma, W and Huang, C and Zhang, W and Mi, G and Miao, Y and Li, X and Gao, Q and Yang, J and Wang, Z and Ye, Y and Guo, S and Lu, J and Huang, J and Lv, S and Sun, Y and Liu, Y and Peng, X and Ren, J and Li, S and Deng, X and Shi, X and Zhang, Q and Yang, Z and Tang, L and Wei, C and Jia, L and Zhang, J and He, M and Tong, Y and Tang, Q and Zhong, X and Liu, Z and Cao, N and Kou, C and Ying, H and Yin, Y and Jiao, X and Zhang, Q and Fan, M and Jiang, R and Zhang, F and Dou, Z}, title = {Pursuing sustainable productivity with millions of smallholder farmers.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {363-366}, pmid = {29513654}, issn = {1476-4687}, mesh = {Agriculture/*methods ; China ; *Conservation of Natural Resources ; Crops, Agricultural/*growth & development ; Decision Support Techniques ; Edible Grain/growth & development ; *Efficiency, Organizational ; Environmental Policy ; *Farmers ; Fertilizers/statistics & numerical data ; Food Supply/methods ; Greenhouse Effect ; Nitrogen/metabolism ; Oryza/growth & development ; Triticum/growth & development ; Zea mays/growth & development ; }, abstract = {Sustainably feeding a growing population is a grand challenge, and one that is particularly difficult in regions that are dominated by smallholder farming. Despite local successes, mobilizing vast smallholder communities with science- and evidence-based management practices to simultaneously address production and pollution problems has been infeasible. Here we report the outcome of concerted efforts in engaging millions of Chinese smallholder farmers to adopt enhanced management practices for greater yield and environmental performance. First, we conducted field trials across China's major agroecological zones to develop locally applicable recommendations using a comprehensive decision-support program. Engaging farmers to adopt those recommendations involved the collaboration of a core network of 1,152 researchers with numerous extension agents and agribusiness personnel. From 2005 to 2015, about 20.9 million farmers in 452 counties adopted enhanced management practices in fields with a total of 37.7 million cumulative hectares over the years. Average yields (maize, rice and wheat) increased by 10.8-11.5%, generating a net grain output of 33 million tonnes (Mt). At the same time, application of nitrogen decreased by 14.7-18.1%, saving 1.2 Mt of nitrogen fertilizers. The increased grain output and decreased nitrogen fertilizer use were equivalent to US$12.2 billion. Estimated reactive nitrogen losses averaged 4.5-4.7 kg nitrogen per Megagram (Mg) with the intervention compared to 6.0-6.4 kg nitrogen per Mg without. Greenhouse gas emissions were 328 kg, 812 kg and 434 kg CO2 equivalent per Mg of maize, rice and wheat produced, respectively, compared to 422 kg, 941 kg and 549 kg CO2 equivalent per Mg without the intervention. On the basis of a large-scale survey (8.6 million farmer participants) and scenario analyses, we further demonstrate the potential impacts of implementing the enhanced management practices on China's food security and sustainability outlook.}, } @article {pmid29513653, year = {2018}, author = {Mayer, C and Hafemeister, C and Bandler, RC and Machold, R and Batista Brito, R and Jaglin, X and Allaway, K and Butler, A and Fishell, G and Satija, R}, title = {Developmental diversification of cortical inhibitory interneurons.}, journal = {Nature}, volume = {555}, number = {7697}, pages = {457-462}, pmid = {29513653}, issn = {1476-4687}, support = {P01 NS074972/NS/NINDS NIH HHS/United States ; R01 MH071679/MH/NIMH NIH HHS/United States ; F31 NS103398/NS/NINDS NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; DP2 HG009623/HG/NHGRI NIH HHS/United States ; F30 MH114462/MH/NIMH NIH HHS/United States ; R01 NS081297/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Cell Differentiation/genetics ; Embryo, Mammalian/cytology ; Female ; Ganglia/cytology/metabolism ; Gene Expression Profiling ; Humans ; Interneurons/*cytology/*physiology ; MEF2 Transcription Factors/metabolism ; Male ; Mice ; Mitosis/genetics ; *Neural Inhibition ; Parvalbumins/metabolism ; RNA, Small Cytoplasmic/genetics ; Single-Cell Analysis ; Visual Cortex/*cytology ; }, abstract = {Diverse subsets of cortical interneurons have vital roles in higher-order brain functions. To investigate how this diversity is generated, here we used single-cell RNA sequencing to profile the transcriptomes of mouse cells collected along a developmental time course. Heterogeneity within mitotic progenitors in the ganglionic eminences is driven by a highly conserved maturation trajectory, alongside eminence-specific transcription factor expression that seeds the emergence of later diversity. Upon becoming postmitotic, progenitors diverge and differentiate into transcriptionally distinct states, including an interneuron precursor state. By integrating datasets across developmental time points, we identified shared sources of transcriptomic heterogeneity between adult interneurons and their precursors, and uncovered the embryonic emergence of cardinal interneuron subtypes. Our analysis revealed that the transcription factor Mef2c, which is linked to various neuropsychiatric and neurodevelopmental disorders, delineates early precursors of parvalbumin-expressing neurons, and is essential for their development. These findings shed new light on the molecular diversification of early inhibitory precursors, and identify gene modules that may influence the specification of human interneuron subtypes.}, } @article {pmid29513652, year = {2018}, author = {Gorthi, A and Romero, JC and Loranc, E and Cao, L and Lawrence, LA and Goodale, E and Iniguez, AB and Bernard, X and Masamsetti, VP and Roston, S and Lawlor, ER and Toretsky, JA and Stegmaier, K and Lessnick, SL and Chen, Y and Bishop, AJR}, title = {EWS-FLI1 increases transcription to cause R-loops and block BRCA1 repair in Ewing sarcoma.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {387-391}, pmid = {29513652}, issn = {1476-4687}, support = {R15 ES019128/ES/NIEHS NIH HHS/United States ; UL1 RR025767/RR/NCRR NIH HHS/United States ; 1R01CA134605/NH/NIH HHS/United States ; R01 CA204915/CA/NCI NIH HHS/United States ; R01 CA140394/CA/NCI NIH HHS/United States ; T32 CA148724/CA/NCI NIH HHS/United States ; 1UL1RR025767-01/NH/NIH HHS/United States ; P30 CA054174/CA/NCI NIH HHS/United States ; K22 ES012264/ES/NIEHS NIH HHS/United States ; R01 CA152063/CA/NCI NIH HHS/United States ; }, mesh = {BRCA1 Protein/*antagonists & inhibitors/metabolism ; Cell Line, Tumor ; DNA Damage ; *Gene Expression Regulation, Neoplastic ; Humans ; *Nucleic Acid Conformation ; Oncogene Proteins, Fusion/genetics/*metabolism ; Proto-Oncogene Protein c-fli-1/genetics/*metabolism ; RNA-Binding Protein EWS/genetics/*metabolism ; *Recombinational DNA Repair ; Sarcoma, Ewing/*genetics/metabolism ; *Transcription, Genetic ; }, abstract = {Ewing sarcoma is an aggressive paediatric cancer of the bone and soft tissue. It results from a chromosomal translocation, predominantly t(11;22)(q24:q12), that fuses the N-terminal transactivation domain of the constitutively expressed EWSR1 protein with the C-terminal DNA binding domain of the rarely expressed FLI1 protein. Ewing sarcoma is highly sensitive to genotoxic agents such as etoposide, but the underlying molecular basis of this sensitivity is unclear. Here we show that Ewing sarcoma cells display alterations in regulation of damage-induced transcription, accumulation of R-loops and increased replication stress. In addition, homologous recombination is impaired in Ewing sarcoma owing to an enriched interaction between BRCA1 and the elongating transcription machinery. Finally, we uncover a role for EWSR1 in the transcriptional response to damage, suppressing R-loops and promoting homologous recombination. Our findings improve the current understanding of EWSR1 function, elucidate the mechanistic basis of the sensitivity of Ewing sarcoma to chemotherapy (including PARP1 inhibitors) and highlight a class of BRCA-deficient-like tumours.}, } @article {pmid29513651, year = {2018}, author = {Yoder, N and Yoshioka, C and Gouaux, E}, title = {Gating mechanisms of acid-sensing ion channels.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {397-401}, pmid = {29513651}, issn = {1476-4687}, support = {R01 NS038631/NS/NINDS NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; T32 DK007680/DK/NIDDK NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; F31 NS096782/NS/NINDS NIH HHS/United States ; }, mesh = {Acid Sensing Ion Channels/*chemistry/*metabolism/ultrastructure ; Animals ; Binding Sites ; CHO Cells ; Chickens ; Cricetulus ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; Ion Channel Gating ; Models, Molecular ; Protein Domains ; Protons ; Sf9 Cells ; Spodoptera ; }, abstract = {Acid-sensing ion channels (ASICs) are trimeric, proton-gated and sodium-selective members of the epithelial sodium channel/degenerin (ENaC/DEG) superfamily of ion channels and are expressed throughout vertebrate central and peripheral nervous systems. Gating of ASICs occurs on a millisecond time scale and the mechanism involves three conformational states: high pH resting, low pH open and low pH desensitized. Existing X-ray structures of ASIC1a describe the conformations of the open and desensitized states, but the structure of the high pH resting state and detailed mechanisms of the activation and desensitization of the channel have remained elusive. Here we present structures of the high pH resting state of homotrimeric chicken (Gallus gallus) ASIC1a, determined by X-ray crystallography and single particle cryo-electron microscopy, and present a comprehensive molecular mechanism for proton-dependent gating in ASICs. In the resting state, the position of the thumb domain is further from the three-fold molecular axis, thereby expanding the 'acidic pocket' in comparison to the open and desensitized states. Activation therefore involves 'closure' of the thumb into the acidic pocket, expansion of the lower palm domain and an iris-like opening of the channel gate. Furthermore, we demonstrate how the β11-β12 linkers that demarcate the upper and lower palm domains serve as a molecular 'clutch', and undergo a simple rearrangement to permit rapid desensitization.}, } @article {pmid29513650, year = {2018}, author = {O'Toole, M and Lindell, DB and Wetzstein, G}, title = {Confocal non-line-of-sight imaging based on the light-cone transform.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {338-341}, pmid = {29513650}, issn = {1476-4687}, abstract = {How to image objects that are hidden from a camera's view is a problem of fundamental importance to many fields of research, with applications in robotic vision, defence, remote sensing, medical imaging and autonomous vehicles. Non-line-of-sight (NLOS) imaging at macroscopic scales has been demonstrated by scanning a visible surface with a pulsed laser and a time-resolved detector. Whereas light detection and ranging (LIDAR) systems use such measurements to recover the shape of visible objects from direct reflections, NLOS imaging reconstructs the shape and albedo of hidden objects from multiply scattered light. Despite recent advances, NLOS imaging has remained impractical owing to the prohibitive memory and processing requirements of existing reconstruction algorithms, and the extremely weak signal of multiply scattered light. Here we show that a confocal scanning procedure can address these challenges by facilitating the derivation of the light-cone transform to solve the NLOS reconstruction problem. This method requires much smaller computational and memory resources than previous reconstruction methods do and images hidden objects at unprecedented resolution. Confocal scanning also provides a sizeable increase in signal and range when imaging retroreflective objects. We quantify the resolution bounds of NLOS imaging, demonstrate its potential for real-time tracking and derive efficient algorithms that incorporate image priors and a physically accurate noise model. Additionally, we describe successful outdoor experiments of NLOS imaging under indirect sunlight.}, } @article {pmid29513649, year = {2018}, author = {Sorrells, SF and Paredes, MF and Cebrian-Silla, A and Sandoval, K and Qi, D and Kelley, KW and James, D and Mayer, S and Chang, J and Auguste, KI and Chang, EF and Gutierrez, AJ and Kriegstein, AR and Mathern, GW and Oldham, MC and Huang, EJ and Garcia-Verdugo, JM and Yang, Z and Alvarez-Buylla, A}, title = {Human hippocampal neurogenesis drops sharply in children to undetectable levels in adults.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {377-381}, pmid = {29513649}, issn = {1476-4687}, support = {U01 MH108898/MH/NIMH NIH HHS/United States ; P01 NS083513/NS/NINDS NIH HHS/United States ; R01 NS028478/NS/NINDS NIH HHS/United States ; T32 GM007618/GM/NIGMS NIH HHS/United States ; K08 NS091537/NS/NINDS NIH HHS/United States ; NS083823/NS/NINDS NIH HHS/United States ; F32 MH103003/MH/NIMH NIH HHS/United States ; R01 NS083823/NS/NINDS NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Animals ; Animals, Newborn ; Cell Count ; Cell Proliferation ; Child ; Child, Preschool ; Dentate Gyrus/cytology/embryology ; Epilepsy/pathology ; Female ; Fetal Development ; Healthy Volunteers ; Hippocampus/anatomy & histology/*cytology/embryology ; Humans ; Infant ; Macaca mulatta ; Male ; Middle Aged ; Neural Stem Cells/cytology ; *Neurogenesis ; Neurons/*cytology ; Young Adult ; }, abstract = {New neurons continue to be generated in the subgranular zone of the dentate gyrus of the adult mammalian hippocampus. This process has been linked to learning and memory, stress and exercise, and is thought to be altered in neurological disease. In humans, some studies have suggested that hundreds of new neurons are added to the adult dentate gyrus every day, whereas other studies find many fewer putative new neurons. Despite these discrepancies, it is generally believed that the adult human hippocampus continues to generate new neurons. Here we show that a defined population of progenitor cells does not coalesce in the subgranular zone during human fetal or postnatal development. We also find that the number of proliferating progenitors and young neurons in the dentate gyrus declines sharply during the first year of life and only a few isolated young neurons are observed by 7 and 13 years of age. In adult patients with epilepsy and healthy adults (18-77 years; n = 17 post-mortem samples from controls; n = 12 surgical resection samples from patients with epilepsy), young neurons were not detected in the dentate gyrus. In the monkey (Macaca mulatta) hippocampus, proliferation of neurons in the subgranular zone was found in early postnatal life, but this diminished during juvenile development as neurogenesis decreased. We conclude that recruitment of young neurons to the primate hippocampus decreases rapidly during the first years of life, and that neurogenesis in the dentate gyrus does not continue, or is extremely rare, in adult humans. The early decline in hippocampal neurogenesis raises questions about how the function of the dentate gyrus differs between humans and other species in which adult hippocampal neurogenesis is preserved.}, } @article {pmid29513384, year = {2018}, author = {Katju, V and Packard, LB and Keightley, PD}, title = {Fitness decline under osmotic stress in Caenorhabditis elegans populations subjected to spontaneous mutation accumulation at varying population sizes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {1000-1008}, doi = {10.1111/evo.13463}, pmid = {29513384}, issn = {1558-5646}, abstract = {The consequences of mutations for population fitness depends on their individual selection coefficients and the effective population size. An earlier study of Caenorhabditis elegans spontaneous mutation accumulation lines evolved for 409 generations at three population sizes found that Ne = 1 populations declined significantly in fitness whereas the fitness of larger populations (Ne = 5, 50) was indistinguishable from the ancestral control under benign conditions. To test if larger MA populations harbor a load of cryptic deleterious mutations that are obscured under benign laboratory conditions, we measured fitness under osmotic stress via exposure to hypersaline conditions. The fitness of Ne = 1 lines exhibited a further decline under osmotic stress compared to benign conditions. However, the fitness of larger populations remained indistinguishable from that of the ancestral control. The average effects of deleterious mutations in Ne = 1 lines were estimated to be 22% for productivity and 14% for survivorship, exceeding values previously detected under benign conditions. Our results suggest that fitness decline is due to large effect mutations that are rapidly removed via selection even in small populations, with implications for conservation practices. Genetic stochasticity may not be as potent and immediate a threat to the persistence of small populations as other demographic and environmental stochastic factors.}, } @article {pmid29512654, year = {2018}, author = {Cao, Y and Fatemi, V and Demir, A and Fang, S and Tomarken, SL and Luo, JY and Sanchez-Yamagishi, JD and Watanabe, K and Taniguchi, T and Kaxiras, E and Ashoori, RC and Jarillo-Herrero, P}, title = {Correlated insulator behaviour at half-filling in magic-angle graphene superlattices.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {80-84}, pmid = {29512654}, issn = {1476-4687}, abstract = {A van der Waals heterostructure is a type of metamaterial that consists of vertically stacked two-dimensional building blocks held together by the van der Waals forces between the layers. This design means that the properties of van der Waals heterostructures can be engineered precisely, even more so than those of two-dimensional materials. One such property is the 'twist' angle between different layers in the heterostructure. This angle has a crucial role in the electronic properties of van der Waals heterostructures, but does not have a direct analogue in other types of heterostructure, such as semiconductors grown using molecular beam epitaxy. For small twist angles, the moiré pattern that is produced by the lattice misorientation between the two-dimensional layers creates long-range modulation of the stacking order. So far, studies of the effects of the twist angle in van der Waals heterostructures have concentrated mostly on heterostructures consisting of monolayer graphene on top of hexagonal boron nitride, which exhibit relatively weak interlayer interaction owing to the large bandgap in hexagonal boron nitride. Here we study a heterostructure consisting of bilayer graphene, in which the two graphene layers are twisted relative to each other by a certain angle. We show experimentally that, as predicted theoretically, when this angle is close to the 'magic' angle the electronic band structure near zero Fermi energy becomes flat, owing to strong interlayer coupling. These flat bands exhibit insulating states at half-filling, which are not expected in the absence of correlations between electrons. We show that these correlated states at half-filling are consistent with Mott-like insulator states, which can arise from electrons being localized in the superlattice that is induced by the moiré pattern. These properties of magic-angle-twisted bilayer graphene heterostructures suggest that these materials could be used to study other exotic many-body quantum phases in two dimensions in the absence of a magnetic field. The accessibility of the flat bands through electrical tunability and the bandwidth tunability through the twist angle could pave the way towards more exotic correlated systems, such as unconventional superconductors and quantum spin liquids.}, } @article {pmid29512653, year = {2018}, author = {Scapin, G and Dandey, VP and Zhang, Z and Prosise, W and Hruza, A and Kelly, T and Mayhood, T and Strickland, C and Potter, CS and Carragher, B}, title = {Structure of the insulin receptor-insulin complex by single-particle cryo-EM analysis.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {122-125}, pmid = {29512653}, issn = {1476-4687}, support = {P41 GM103310/GM/NIGMS NIH HHS/United States ; P41 RR017573/RR/NCRR NIH HHS/United States ; S10 OD019994/OD/NIH HHS/United States ; }, mesh = {Apoproteins/chemistry/metabolism ; *Cryoelectron Microscopy ; Crystallography, X-Ray ; Humans ; Insulin/*chemistry/*metabolism ; Models, Molecular ; *Protein Multimerization ; Receptor, Insulin/*chemistry/metabolism/*ultrastructure ; Signal Transduction ; Single Molecule Imaging ; }, abstract = {The insulin receptor is a dimeric protein that has a crucial role in controlling glucose homeostasis, regulating lipid, protein and carbohydrate metabolism, and modulating brain neurotransmitter levels. Insulin receptor dysfunction has been associated with many diseases, including diabetes, cancer and Alzheimer's disease. The primary sequence of the receptor has been known since the 1980s, and is composed of an extracellular portion (the ectodomain, ECD), a single transmembrane helix and an intracellular tyrosine kinase domain. Binding of insulin to the dimeric ECD triggers auto-phosphorylation of the tyrosine kinase domain and subsequent activation of downstream signalling molecules. Biochemical and mutagenesis data have identified two putative insulin-binding sites, S1 and S2. The structures of insulin bound to an ECD fragment containing S1 and of the apo ectodomain have previously been reported, but details of insulin binding to the full receptor and the signal propagation mechanism are still not understood. Here we report single-particle cryo-electron microscopy reconstructions of the 1:2 (4.3 Å) and 1:1 (7.4 Å) complexes of the insulin receptor ECD dimer with insulin. The symmetrical 4.3 Å structure shows two insulin molecules per dimer, each bound between the leucine-rich subdomain L1 of one monomer and the first fibronectin-like domain (FnIII-1) of the other monomer, and making extensive interactions with the α-subunit C-terminal helix (α-CT helix). The 7.4 Å structure has only one similarly bound insulin per receptor dimer. The structures confirm the binding interactions at S1 and define the full S2 binding site. These insulin receptor states suggest that recruitment of the α-CT helix upon binding of the first insulin changes the relative subdomain orientations and triggers downstream signal propagation.}, } @article {pmid29512652, year = {2018}, author = {Hu, JH and Miller, SM and Geurts, MH and Tang, W and Chen, L and Sun, N and Zeina, CM and Gao, X and Rees, HA and Lin, Z and Liu, DR}, title = {Evolved Cas9 variants with broad PAM compatibility and high DNA specificity.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {57-63}, pmid = {29512652}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 EB022376/EB/NIBIB NIH HHS/United States ; R35 GM118062/GM/NIGMS NIH HHS/United States ; RM1 HG009490/HG/NHGRI NIH HHS/United States ; }, mesh = {CRISPR-Associated Proteins/*genetics/*metabolism ; CRISPR-Cas Systems/*genetics ; DNA/*genetics/*metabolism ; DNA Cleavage ; Deoxyribonucleases/metabolism ; Directed Molecular Evolution ; Gene Editing/*methods ; Genome, Human/genetics ; HEK293 Cells ; Humans ; *Mutation ; Nucleotide Motifs ; Streptococcus pyogenes/enzymology/genetics ; Substrate Specificity/*genetics ; Transcriptional Activation ; }, abstract = {A key limitation of the use of the CRISPR-Cas9 system for genome editing and other applications is the requirement that a protospacer adjacent motif (PAM) be present at the target site. For the most commonly used Cas9 from Streptococcus pyogenes (SpCas9), the required PAM sequence is NGG. No natural or engineered Cas9 variants that have been shown to function efficiently in mammalian cells offer a PAM less restrictive than NGG. Here we use phage-assisted continuous evolution to evolve an expanded PAM SpCas9 variant (xCas9) that can recognize a broad range of PAM sequences including NG, GAA and GAT. The PAM compatibility of xCas9 is the broadest reported, to our knowledge, among Cas9 proteins that are active in mammalian cells, and supports applications in human cells including targeted transcriptional activation, nuclease-mediated gene disruption, and cytidine and adenine base editing. Notably, despite its broadened PAM compatibility, xCas9 has much greater DNA specificity than SpCas9, with substantially lower genome-wide off-target activity at all NGG target sites tested, as well as minimal off-target activity when targeting genomic sites with non-NGG PAMs. These findings expand the DNA targeting scope of CRISPR systems and establish that there is no necessary trade-off between Cas9 editing efficiency, PAM compatibility and DNA specificity.}, } @article {pmid29512651, year = {2018}, author = {Cao, Y and Fatemi, V and Fang, S and Watanabe, K and Taniguchi, T and Kaxiras, E and Jarillo-Herrero, P}, title = {Unconventional superconductivity in magic-angle graphene superlattices.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {43-50}, pmid = {29512651}, issn = {1476-4687}, abstract = {The behaviour of strongly correlated materials, and in particular unconventional superconductors, has been studied extensively for decades, but is still not well understood. This lack of theoretical understanding has motivated the development of experimental techniques for studying such behaviour, such as using ultracold atom lattices to simulate quantum materials. Here we report the realization of intrinsic unconventional superconductivity-which cannot be explained by weak electron-phonon interactions-in a two-dimensional superlattice created by stacking two sheets of graphene that are twisted relative to each other by a small angle. For twist angles of about 1.1°-the first 'magic' angle-the electronic band structure of this 'twisted bilayer graphene' exhibits flat bands near zero Fermi energy, resulting in correlated insulating states at half-filling. Upon electrostatic doping of the material away from these correlated insulating states, we observe tunable zero-resistance states with a critical temperature of up to 1.7 kelvin. The temperature-carrier-density phase diagram of twisted bilayer graphene is similar to that of copper oxides (or cuprates), and includes dome-shaped regions that correspond to superconductivity. Moreover, quantum oscillations in the longitudinal resistance of the material indicate the presence of small Fermi surfaces near the correlated insulating states, in analogy with underdoped cuprates. The relatively high superconducting critical temperature of twisted bilayer graphene, given such a small Fermi surface (which corresponds to a carrier density of about 1011 per square centimetre), puts it among the superconductors with the strongest pairing strength between electrons. Twisted bilayer graphene is a precisely tunable, purely carbon-based, two-dimensional superconductor. It is therefore an ideal material for investigations of strongly correlated phenomena, which could lead to insights into the physics of high-critical-temperature superconductors and quantum spin liquids.}, } @article {pmid29512650, year = {2018}, author = {Sanghai, ZA and Miller, L and Molloy, KR and Barandun, J and Hunziker, M and Chaker-Margot, M and Wang, J and Chait, BT and Klinge, S}, title = {Modular assembly of the nucleolar pre-60S ribosomal subunit.}, journal = {Nature}, volume = {556}, number = {7699}, pages = {126-129}, pmid = {29512650}, issn = {1476-4687}, support = {DP2 GM123459/GM/NIGMS NIH HHS/United States ; T32 GM115327/GM/NIGMS NIH HHS/United States ; P41 GM103314/GM/NIGMS NIH HHS/United States ; P41 GM109824/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Nucleolus/*chemistry ; Cross-Linking Reagents/chemistry ; *Cryoelectron Microscopy ; Models, Molecular ; Molecular Mimicry ; Protein Domains ; Protein Stability ; RNA Folding ; RNA, Ribosomal/chemistry/genetics/metabolism/ultrastructure ; Reproducibility of Results ; Ribosomal Proteins/chemistry/metabolism/ultrastructure ; Ribosome Subunits, Large, Eukaryotic/chemistry/*metabolism/*ultrastructure ; *Saccharomyces cerevisiae/chemistry/genetics/ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/metabolism/ultrastructure ; }, abstract = {Early co-transcriptional events during eukaryotic ribosome assembly result in the formation of precursors of the small (40S) and large (60S) ribosomal subunits. A multitude of transient assembly factors regulate and chaperone the systematic folding of pre-ribosomal RNA subdomains. However, owing to a lack of structural information, the role of these factors during early nucleolar 60S assembly is not fully understood. Here we report cryo-electron microscopy (cryo-EM) reconstructions of the nucleolar pre-60S ribosomal subunit in different conformational states at resolutions of up to 3.4 Å. These reconstructions reveal how steric hindrance and molecular mimicry are used to prevent both premature folding states and binding of later factors. This is accomplished by the concerted activity of 21 ribosome assembly factors that stabilize and remodel pre-ribosomal RNA and ribosomal proteins. Among these factors, three Brix-domain proteins and their binding partners form a ring-like structure at ribosomal RNA (rRNA) domain boundaries to support the architecture of the maturing particle. The existence of mutually exclusive conformations of these pre-60S particles suggests that the formation of the polypeptide exit tunnel is achieved through different folding pathways during subsequent stages of ribosome assembly. These structures rationalize previous genetic and biochemical data and highlight the mechanisms that drive eukaryotic ribosome assembly in a unidirectional manner.}, } @article {pmid29511873, year = {2018}, author = {Risa, A and Krifaton, C and Kukolya, J and Kriszt, B and Cserháti, M and Táncsics, A}, title = {Aflatoxin B1 and Zearalenone-Detoxifying Profile of Rhodococcus Type Strains.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {907-917}, pmid = {29511873}, issn = {1432-0991}, support = {NVKP_16-1-2016-0009//National Research, Development and Innovation Office (HUN)/ ; VKSZ-12-1-2013-0078//National Research, Development and Innovation Office (HUN)/ ; }, mesh = {Aflatoxin B1/*metabolism ; Biodegradation, Environmental ; Rhodococcus/classification/*metabolism ; Zearalenone/*metabolism ; }, abstract = {Aflatoxin B1 (AFB1) and zearalenone (ZON) are dangerous mycotoxins due to their carcinogenicity or oestrogenicity. To alleviate negative effects on humans and animals, successful detoxification tools are needed. The application of microorganisms to biodegrade mycotoxins can be an effective way in food and feed industry enhancing food safety. Several Rhodococcus strains are effective in the degradation of aromatic mycotoxins and their application in mycotoxin biodetoxification processes is a promising field of biotechnology. In this study, we investigated the AFB1 and ZON detoxification ability of 42 type strains of Rhodococcus species. Samples were analysed by high-performance liquid chromatograph equipped with fluorescence detector for mycotoxin concentration and SOS-chromotest was used for monitoring remaining genotoxicity. Out of the 42 Rhodococcus strains, 18 could eliminate more than 90% of the applied AFB1 and the genotoxicity was ceased by 15 strains in 72 h (R. imtechensis JCM 13270T, R. erythropolis JCM 3201T, R. tukisamuensis JCM 11308T, R. rhodnii JCM 3203T, R. aerolatus JCM 19485T, R. enclensis DSM 45688T, R. lactis DSM 45625T, R. trifolii DSM 45580T, R. qingshengii DSM 45222T, R. artemisiae DSM 45380T, R. baikonurensis DSM 44587T, R. globerulus JCM 7472T, R. kroppenstedtii JCM 13011T, R. pyridinivorans JCM 10940T, R. corynebacterioides JCM 3376T). In case of ZON, only R. percolatus JCM 10087T was able to degrade more than 90% of the compound and to reduce the oestrogenicity with 70%.}, } @article {pmid29511851, year = {2018}, author = {Boyan, G and Graf, P and Ehrhardt, E}, title = {Patterns of cell death in the embryonic antenna of the grasshopper Schistocerca gregaria.}, journal = {Development genes and evolution}, volume = {228}, number = {2}, pages = {105-118}, pmid = {29511851}, issn = {1432-041X}, mesh = {Animals ; Apoptosis ; Arthropod Antennae/embryology/*physiology ; Cell Differentiation ; Cell Lineage ; Cells, Cultured ; Embryonic Development ; Epithelial Cells/cytology ; Grasshoppers/*cytology/embryology/*physiology ; Neurons/cytology ; }, abstract = {We have investigated the pattern of apoptosis in the antennal epithelium during embryonic development of the grasshopper Schistocerca gregaria. The molecular labels lachesin and annulin reveal that the antennal epithelium becomes subdivided into segment-like meristal annuli within which sensory cell clusters later differentiate. To determine whether apoptosis is involved in the development of such sensory cell clusters, we examined the expression pattern of the cell death labels acridine orange and TUNEL in the epithelium. We found stereotypic, age-dependent, wave-like patterns of cell death in the antenna. Early in embryogenesis, apoptosis is restricted to the most basal meristal annuli but subsequently spreads to encompass almost the entire antenna. Cell death then declines in more basal annuli and is only found in the tip region later in embryogenesis. Apoptosis is restricted throughout to the midregion of a given annulus and away from its border with neighboring annuli, arguing against a causal role in annular formation. Double-labeling for cell death and sensory cell differentiation reveals apoptosis occurring within bands of differentiating sensory cell clusters, matching the meristal organization of the apical antenna. Examination of the individual epithelial lineages which generate sensory cells reveals that apoptosis begins peripherally within a lineage and with age expands to encompass the differentiated sensory cell at the base. We conclude that complete lineages can undergo apoptosis and that the youngest cells in these lineages appear to die first, with the sensory neuron dying last. Lineage-based death in combination with cell death patterns in different regions of the antenna may contribute to odor-mediated behaviors in the grasshopper.}, } @article {pmid29511354, year = {2018}, author = {Yu, X and Reva, ON}, title = {SWPhylo - A Novel Tool for Phylogenomic Inferences by Comparison of Oligonucleotide Patterns and Integration of Genome-Based and Gene-Based Phylogenetic Trees.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318759299}, pmid = {29511354}, issn = {1176-9343}, abstract = {Modern phylogenetic studies may benefit from the analysis of complete genome sequences of various microorganisms. Evolutionary inferences based on genome-scale analysis are believed to be more accurate than the gene-based alternative. However, the computational complexity of current phylogenomic procedures, inappropriateness of standard phylogenetic tools to process genome-wide data, and lack of reliable substitution models which correlates with alignment-free phylogenomic approaches deter microbiologists from using these opportunities. For example, the super-matrix and super-tree approaches of phylogenomics use multiple integrated genomic loci or individual gene-based trees to infer an overall consensus tree. However, these approaches potentially multiply errors of gene annotation and sequence alignment not mentioning the computational complexity and laboriousness of the methods. In this article, we demonstrate that the annotation- and alignment-free comparison of genome-wide tetranucleotide frequencies, termed oligonucleotide usage patterns (OUPs), allowed a fast and reliable inference of phylogenetic trees. These were congruent to the corresponding whole genome super-matrix trees in terms of tree topology when compared with other known approaches including 16S ribosomal RNA and GyrA protein sequence comparison, complete genome-based MAUVE, and CVTree methods. A Web-based program to perform the alignment-free OUP-based phylogenomic inferences was implemented at http://swphylo.bi.up.ac.za/. Applicability of the tool was tested on different taxa from subspecies to intergeneric levels. Distinguishing between closely related taxonomic units may be enforced by providing the program with alignments of marker protein sequences, eg, GyrA.}, } @article {pmid29511353, year = {2018}, author = {Khan, AR and Pervez, MT and Babar, ME and Naveed, N and Shoaib, M}, title = {A Comprehensive Study of De Novo Genome Assemblers: Current Challenges and Future Prospective.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318758650}, pmid = {29511353}, issn = {1176-9343}, abstract = {Background: Current advancements in next-generation sequencing technology have made possible to sequence whole genome but assembling a large number of short sequence reads is still a big challenge. In this article, we present the comparative study of seven assemblers, namely, ABySS, Velvet, Edena, SGA, Ray, SSAKE, and Perga, using prokaryotic and eukaryotic paired-end as well as single-end data sets from Illumina platform.

Results: Results showed that in case of single-end data sets, Velvet and ABySS outperformed in all the seven assemblers with comparatively low assembling time and high genome fraction. Velvet consumed the least amount of memory than any other assembler. In case of paired-end data sets, Velvet consumed least amount of time and produced high genome fraction after ABySS and Ray. In terms of low memory usage, SGA and Edena outperformed in all the assemblers. Ray also showed good genome fraction; however, extremely high assembling time consumed by the Ray might make it prohibitively slow on larger data sets of single and paired-end data.

Conclusions: Our comparison study will provide assistance to the scientists for selecting the suitable assembler according to their data sets and will also assist the developers to upgrade or develop a new assembler for de novo assembling.}, } @article {pmid29511285, year = {2018}, author = {Leitch, HG and Hajkova, P}, title = {Eggs sense high-fat diet.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {318-319}, doi = {10.1038/s41588-018-0068-1}, pmid = {29511285}, issn = {1546-1718}, support = {MC_U120092689//Medical Research Council/United Kingdom ; }, } @article {pmid29511284, year = {2018}, author = {Wijmenga, C and Zhernakova, A}, title = {The importance of cohort studies in the post-GWAS era.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {322-328}, doi = {10.1038/s41588-018-0066-3}, pmid = {29511284}, issn = {1546-1718}, abstract = {The past decade has seen enormous success of wide-scale genetic studies in identifying genetic variants that modify individuals' predisposition to common diseases. However, the interpretation and functional understanding of these variants lag far behind. In this Perspective, we discuss opportunities for using large-scale cohort studies to investigate the downstream molecular effects of SNPs at different 'omics' data levels. We point to the pivotal role of population cohorts in establishing causality and advancing drug discovery. In particular, we focus on the breadth-versus-depth concepts of population studies, on data harmonization, and on the challenges, ethical aspects and future perspectives of cohort studies.}, } @article {pmid29511283, year = {2018}, author = {Evans, DM}, title = {Elucidating the genetics of craniofacial shape.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {319-321}, doi = {10.1038/s41588-018-0065-4}, pmid = {29511283}, issn = {1546-1718}, } @article {pmid29511275, year = {2018}, author = {Thomas, JA and Tan, MSY and Bisson, C and Borg, A and Umrekar, TR and Hackett, F and Hale, VL and Vizcay-Barrena, G and Fleck, RA and Snijders, AP and Saibil, HR and Blackman, MJ}, title = {Publisher Correction: A protease cascade regulates release of the human malaria parasite Plasmodium falciparum from host red blood cells.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {523}, doi = {10.1038/s41564-018-0134-6}, pmid = {29511275}, issn = {2058-5276}, abstract = {In the version of this Letter originally published, Michele S. Y. Tan was incorrectly listed as Michele Y. S. Tan due to a technical error. This has now been amended in all online versions of the Letter.}, } @article {pmid29511124, year = {2018}, author = {Willoughby, L}, title = {News Feature: Can predators have a big impact on carbon emissions calculations?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2260-2263}, pmid = {29511124}, issn = {1091-6490}, mesh = {Animals ; Carbon Dioxide/*metabolism ; Carbon Footprint ; Ecology ; *Food Chain ; *Global Warming ; Kelp/physiology ; *Models, Statistical ; Otters/physiology ; Predatory Behavior/*physiology ; Sea Urchins/physiology ; Wolves/physiology ; }, } @article {pmid29511107, year = {2018}, author = {Schlesinger, WH and Klein, EM and Vengosh, A}, title = {Reply to Selin: Human impacts on the atmospheric burden of trace metals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2668}, pmid = {29511107}, issn = {1091-6490}, mesh = {Air Pollutants/*analysis ; Environmental Monitoring ; Humans ; Metals/analysis ; Metals, Heavy ; Trace Elements/*analysis ; }, } @article {pmid29511106, year = {2018}, author = {Taschereau-Dumouchel, V and Cortese, A and Chiba, T and Knotts, JD and Kawato, M and Lau, H}, title = {Towards an unconscious neural reinforcement intervention for common fears.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3470-3475}, pmid = {29511106}, issn = {1091-6490}, support = {R01 NS088628/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; Animals ; Brain/*physiology ; Brain Mapping ; Double-Blind Method ; Fear/*physiology ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Phobic Disorders/*physiopathology ; Photic Stimulation ; *Reinforcement (Psychology) ; *Unconsciousness ; Young Adult ; }, abstract = {Can "hardwired" physiological fear responses (e.g., for spiders and snakes) be reprogramed unconsciously in the human brain? Currently, exposure therapy is among the most effective treatments for anxiety disorders, but this intervention is subjectively aversive to patients, causing many to drop out of treatment prematurely. Here we introduce a method to bypass the subjective unpleasantness in conscious exposure, by directly pairing monetary reward with unconscious occurrences of decoded representations of naturally feared animals in the brain. To decode physiological fear representations without triggering excessively aversive reactions, we capitalize on recent advancements in functional magnetic resonance imaging decoding techniques, and use a method called hyperalignment to infer the relevant representations of feared animals for a designated participant based on data from other "surrogate" participants. In this way, the procedure completely bypasses the need for a conscious encounter with feared animals. We demonstrate that our method can lead to reliable reductions in physiological fear responses, as measured by skin conductance as well as amygdala hemodynamic activity. Not only do these results raise the intriguing possibility that naturally occurring fear responses can be "reprogrammed" outside of conscious awareness, importantly, they also create the rare opportunity to rigorously test a psychological intervention of this nature in a double-blind, placebo-controlled fashion. This may pave the way for a new approach combining the appealing rationale and proven efficacy of conventional psychotherapy with the rigor and leverage of clinical neuroscience.}, } @article {pmid29511105, year = {2018}, author = {An, S and Kim, B and Kwon, S and Moon, G and Lee, M and Jhe, W}, title = {Bifurcation-enhanced ultrahigh sensitivity of a buckled cantilever.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2884-2889}, pmid = {29511105}, issn = {1091-6490}, abstract = {Buckling, first introduced by Euler in 1744 [Euler L (1744) Opera Omnia I 24:231], a sudden mechanical sideways deflection of a structural member under compressive stress, represents a bifurcation in the solution to the equations of static equilibrium. Although it has been investigated in diverse research areas, such a common nonlinear phenomenon may be useful to devise a unique mechanical sensor that addresses the still-challenging features, such as the enhanced sensitivity and polarization-dependent detection capability. We demonstrate the bifurcation-enhanced sensitive measurement of mechanical vibrations using the nonlinear buckled cantilever tip in ambient conditions. The cantilever, initially buckled with its tip pinned, flips its buckling near the bifurcation point (BP), where the buckled tip becomes softened. The enhanced mechanical sensitivity results from the increasing fluctuations, unlike the typical linear sensors, which facilitate the noise-induced buckling-to-flipping transition of the softened cantilever. This allows the in situ continuous or repeated single-shot detection of the surface acoustic waves of different polarizations without any noticeable wear of the tip. We obtained the sensitivity above 106 V(m/s)-1, a 1,000-fold enhancement over the conventional seismometers. Our results lead to development of mechanical sensors of high sensitivity, reproducibility, and durability, which may be applied to detect, e.g., the directional surface waves on the laboratory as well as the geological scale.}, } @article {pmid29511104, year = {2018}, author = {Seo, Y and Kingsley, S and Walker, G and Mondoux, MA and Tissenbaum, HA}, title = {Metabolic shift from glycogen to trehalose promotes lifespan and healthspan in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2791-E2800}, pmid = {29511104}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 AG025891/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Autophagy/physiology ; Caenorhabditis elegans/drug effects/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/metabolism ; Forkhead Transcription Factors/genetics/metabolism ; Glucose/metabolism/toxicity ; Glycogen/genetics/*metabolism ; Longevity ; Time Factors ; Trehalose/genetics/*metabolism ; }, abstract = {As Western diets continue to include an ever-increasing amount of sugar, there has been a rise in obesity and type 2 diabetes. To avoid metabolic diseases, the body must maintain proper metabolism, even on a high-sugar diet. In both humans and Caenorhabditis elegans, excess sugar (glucose) is stored as glycogen. Here, we find that animals increased stored glycogen as they aged, whereas even young adult animals had increased stored glycogen on a high-sugar diet. Decreasing the amount of glycogen storage by modulating the C. elegans glycogen synthase, gsy-1, a key enzyme in glycogen synthesis, can extend lifespan, prolong healthspan, and limit the detrimental effects of a high-sugar diet. Importantly, limiting glycogen storage leads to a metabolic shift whereby glucose is now stored as trehalose. Two additional means to increase trehalose show similar longevity extension. Increased trehalose is entirely dependent on a functional FOXO transcription factor DAF-16 and autophagy to promote lifespan and healthspan extension. Our results reveal that when glucose is stored as glycogen, it is detrimental, whereas, when stored as trehalose, animals live a longer, healthier life if DAF-16 is functional. Taken together, these results demonstrate that trehalose modulation may be an avenue for combatting high-sugar-diet pathology.}, } @article {pmid29511103, year = {2018}, author = {Lorenzi, M and Altmann, A and Gutman, B and Wray, S and Arber, C and Hibar, DP and Jahanshad, N and Schott, JM and Alexander, DC and Thompson, PM and Ourselin, S and , }, title = {Susceptibility of brain atrophy to TRIB3 in Alzheimer's disease, evidence from functional prioritization in imaging genetics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3162-3167}, pmid = {29511103}, issn = {1091-6490}, support = {RF1 AG041915/AG/NIA NIH HHS/United States ; R01 AG040060/AG/NIA NIH HHS/United States ; U01 AG024904/AG/NIA NIH HHS/United States ; //Department of Health/United Kingdom ; U54 EB020403/EB/NIBIB NIH HHS/United States ; //CIHR/Canada ; MR/L023784/1//Medical Research Council/United Kingdom ; MR/L016311/1//Medical Research Council/United Kingdom ; MR/J01107X/1//Medical Research Council/United Kingdom ; }, mesh = {Aged ; Alzheimer Disease/diagnostic imaging/*genetics/pathology ; Atrophy/diagnostic imaging/genetics/metabolism ; Brain/diagnostic imaging/*pathology ; Cell Cycle Proteins/*genetics ; Cognitive Dysfunction/diagnostic imaging/genetics/pathology ; Cohort Studies ; Female ; Genetic Predisposition to Disease ; Humans ; Magnetic Resonance Imaging ; Male ; Multivariate Analysis ; Polymorphism, Single Nucleotide ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/genetics ; Repressor Proteins/*genetics ; }, abstract = {The joint modeling of brain imaging information and genetic data is a promising research avenue to highlight the functional role of genes in determining the pathophysiological mechanisms of Alzheimer's disease (AD). However, since genome-wide association (GWA) studies are essentially limited to the exploration of statistical correlations between genetic variants and phenotype, the validation and interpretation of the findings are usually nontrivial and prone to false positives. To address this issue, in this work, we investigate the functional genetic mechanisms underlying brain atrophy in AD by studying the involvement of candidate variants in known genetic regulatory functions. This approach, here termed functional prioritization, aims at testing the sets of gene variants identified by high-dimensional multivariate statistical modeling with respect to known biological processes to introduce a biology-driven validation scheme. When applied to the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort, the functional prioritization allowed for identifying a link between tribbles pseudokinase 3 (TRIB3) and the stereotypical pattern of gray matter loss in AD, which was confirmed in an independent validation sample, and that provides evidence about the relation between this gene and known mechanisms of neurodegeneration.}, } @article {pmid29511102, year = {2018}, author = {Qu, Y and Easson, MEAM and Simionescu, R and Hajicek, J and Thamm, AMK and Salim, V and De Luca, V}, title = {Solution of the multistep pathway for assembly of corynanthean, strychnos, iboga, and aspidosperma monoterpenoid indole alkaloids from 19E-geissoschizine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3180-3185}, pmid = {29511102}, issn = {1091-6490}, mesh = {Aspidosperma/genetics/metabolism ; Carbolines/*metabolism ; Catharanthus/genetics/*metabolism ; Enzymes/genetics/metabolism ; Gene Expression Regulation, Plant ; Gene Silencing ; Indole Alkaloids/*metabolism ; NADP/metabolism ; Plant Proteins/*genetics/metabolism ; Quinolines/metabolism ; Strychnos/metabolism ; Tabernaemontana/metabolism ; Vinca Alkaloids/metabolism ; }, abstract = {Monoterpenoid indole alkaloids (MIAs) possess a diversity of alkaloid skeletons whose biosynthesis is poorly understood. A bioinformatic search of candidate genes, combined with their virus-induced gene silencing, targeted MIA profiling and in vitro/in vivo pathway reconstitution identified and functionally characterized six genes as well as a seventh enzyme reaction required for the conversion of 19E-geissoschizine to tabersonine and catharanthine. The involvement of pathway intermediates in the formation of four MIA skeletons is described, and the role of stemmadenine-O-acetylation in providing necessary reactive substrates for the formation of iboga and aspidosperma MIAs is described. The results enable the assembly of complex dimeric MIAs used in cancer chemotherapy and open the way to production of many other biologically active MIAs that are not easily available from nature.}, } @article {pmid29511101, year = {2018}, author = {Kurup, N and Li, Y and Goncharov, A and Jin, Y}, title = {Intermediate filament accumulation can stabilize microtubules in Caenorhabditis elegans motor neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3114-3119}, pmid = {29511101}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Axonal Transport ; Caenorhabditis elegans/*physiology ; Caenorhabditis elegans Proteins/metabolism ; Cytoskeleton/metabolism ; Gene Expression Regulation/physiology ; Intermediate Filament Proteins/genetics/*metabolism ; Microtubules/*physiology ; Motor Neurons/cytology/*physiology ; Synapses/physiology ; }, abstract = {Neural circuits utilize a coordinated cellular machinery to form and eliminate synaptic connections, with the neuronal cytoskeleton playing a prominent role. During larval development of Caenorhabditis elegans, synapses of motor neurons are stereotypically rewired through a process facilitated by dynamic microtubules (MTs). Through a genetic suppressor screen on mutant animals that fail to rewire synapses, and in combination with live imaging and ultrastructural studies, we find that intermediate filaments (IFs) stabilize MTs to prevent synapse rewiring. Genetic ablation of IFs or pharmacological disruption of IF networks restores MT growth and rescues synapse rewiring defects in the mutant animals, indicating that IF accumulation directly alters MT stability. Our work sheds light on the impact of IFs on MT dynamics and axonal transport, which is relevant to the mechanistic understanding of several human motor neuron diseases characterized by IF accumulation in axonal swellings.}, } @article {pmid29511100, year = {2018}, author = {Obolski, U and Lourenço, J and Thompson, C and Thompson, R and Gori, A and Gupta, S}, title = {Vaccination can drive an increase in frequencies of antibiotic resistance among nonvaccine serotypes of Streptococcus pneumoniae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3102-3107}, pmid = {29511100}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/pharmacology ; Computer Simulation ; *Drug Resistance, Bacterial ; Humans ; Models, Biological ; Pneumococcal Infections/*prevention & control ; Pneumococcal Vaccines/*immunology ; Serogroup ; Streptococcus pneumoniae/classification/*drug effects ; Vaccination ; Vaccines, Conjugate ; }, abstract = {The bacterial pathogen Streptococcus pneumoniae is a major public health concern, being responsible for more than 1.5 million deaths annually through pneumonia, meningitis, and septicemia. Available vaccines target only a subset of serotypes, so vaccination is often accompanied by a rise in the frequency of nonvaccine serotypes. Epidemiological studies suggest that such a change in serotype frequencies is often coupled with an increase of antibiotic resistance among nonvaccine serotypes. Building on previous multilocus models for bacterial pathogen population structure, we have developed a theoretical framework incorporating variation of serotype and antibiotic resistance to examine how their associations may be affected by vaccination. Using this framework, we find that vaccination can result in a rapid increase in the frequency of preexisting resistant variants of nonvaccine serotypes due to the removal of competition from vaccine serotypes.}, } @article {pmid29511099, year = {2018}, author = {Pavillon, N and Hobro, AJ and Akira, S and Smith, NI}, title = {Noninvasive detection of macrophage activation with single-cell resolution through machine learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2676-E2685}, pmid = {29511099}, issn = {1091-6490}, mesh = {Animals ; Dose-Response Relationship, Drug ; Image Processing, Computer-Assisted/*methods ; Lipopolysaccharides/administration & dosage/pharmacology ; *Machine Learning ; Macrophage Activation/drug effects/*physiology ; Mice ; Microscopy, Fluorescence/methods ; Models, Biological ; Progesterone/pharmacology ; RAW 264.7 Cells ; Single-Cell Analysis/methods ; Spectrum Analysis, Raman/*methods ; }, abstract = {We present a method enabling the noninvasive study of minute cellular changes in response to stimuli, based on the acquisition of multiple parameters through label-free microscopy. The retrieved parameters are related to different attributes of the cell. Morphological variables are extracted from quantitative phase microscopy and autofluorescence images, while molecular indicators are retrieved via Raman spectroscopy. We show that these independent parameters can be used to build a multivariate statistical model based on logistic regression, which we apply to the detection at the single-cell level of macrophage activation induced by lipopolysaccharide (LPS) exposure and compare their respective performance in assessing the individual cellular state. The models generated from either morphology or Raman can reliably and independently detect the activation state of macrophage cells, which is validated by comparison with their cytokine secretion and intracellular expression of molecules related to the immune response. The independent models agree on the degree of activation, showing that the features provide insight into the cellular response heterogeneity. We found that morphological indicators are linked to the phenotype, which is mostly related to downstream effects, making the results obtained with these variables dose-dependent. On the other hand, Raman indicators are representative of upstream intracellular molecular changes related to specific activation pathways. By partially inhibiting the LPS-induced activation using progesterone, we could identify several subpopulations, showing the ability of our approach to identify the effect of LPS activation, specific inhibition of LPS, and also the effect of progesterone alone on macrophage cells.}, } @article {pmid29511098, year = {2018}, author = {Nguyen, AD and Nguyen, TA and Zhang, J and Devireddy, S and Zhou, P and Karydas, AM and Xu, X and Miller, BL and Rigo, F and Ferguson, SM and Huang, EJ and Walther, TC and Farese, RV}, title = {Murine knockin model for progranulin-deficient frontotemporal dementia with nonsense-mediated mRNA decay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2849-E2858}, pmid = {29511098}, issn = {1091-6490}, support = {P50 AG023501/AG/NIA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; I01 BX002978/BX/BLRD VA/United States ; P50 AG047270/AG/NIA NIH HHS/United States ; R00 AG047339/AG/NIA NIH HHS/United States ; R01 GM105718/GM/NIGMS NIH HHS/United States ; K99 AG047339/AG/NIA NIH HHS/United States ; C06 RR018928/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Fibroblasts/drug effects ; Frontotemporal Dementia/*etiology/genetics ; Gene Knock-In Techniques ; Humans ; Intercellular Signaling Peptides and Proteins/*genetics/metabolism ; Lysosomes/genetics/metabolism ; Mice, Inbred C57BL ; *Mutation ; Nonsense Mediated mRNA Decay/*drug effects ; Oligonucleotides, Antisense/pharmacology ; Progranulins ; RNA, Messenger ; }, abstract = {Frontotemporal dementia (FTD) is the most common neurodegenerative disorder in individuals under age 60 and has no treatment or cure. Because many cases of FTD result from GRN nonsense mutations, an animal model for this type of mutation is highly desirable for understanding pathogenesis and testing therapies. Here, we generated and characterized GrnR493X knockin mice, which model the most common human GRN mutation, a premature stop codon at arginine 493 (R493X). Homozygous GrnR493X mice have markedly reduced Grn mRNA levels, lack detectable progranulin protein, and phenocopy Grn knockout mice, with CNS microgliosis, cytoplasmic TDP-43 accumulation, reduced synaptic density, lipofuscinosis, hyperinflammatory macrophages, excessive grooming behavior, and reduced survival. Inhibition of nonsense-mediated mRNA decay (NMD) by genetic, pharmacological, or antisense oligonucleotide-based approaches showed that NMD contributes to the reduced mRNA levels in GrnR493X mice and cell lines and in fibroblasts from patients containing the GRNR493X mutation. Moreover, the expressed truncated R493X mutant protein was functional in several assays in progranulin-deficient cells. Together, these findings establish a murine model for in vivo testing of NMD inhibition or other therapies as potential approaches for treating progranulin deficiency caused by the R493X mutation.}, } @article {pmid29511097, year = {2018}, author = {Selin, NE}, title = {Anthropogenic enrichment of mercury greater than that of vanadium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2666-E2667}, pmid = {29511097}, issn = {1091-6490}, mesh = {Environmental Monitoring ; Mercury/*analysis ; Vanadium/*analysis ; }, } @article {pmid29510761, year = {2018}, author = {Encheva, V and Foltz, C and Snijders, AP and Frickel, EM}, title = {Murine Gbp1 and Gbp2 are ubiquitinated independent of Toxoplasma gondii infection.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {166}, pmid = {29510761}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; MC_UP_1202/12//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Embryo, Mammalian ; Fibroblasts ; GTP-Binding Proteins/*metabolism ; Mice ; Mice, Inbred C57BL ; *Toxoplasmosis ; *Ubiquitination ; }, abstract = {OBJECTIVE: The intracellular parasite Toxoplasma gondii can invade any nucleated cell residing inside a parasitophorous vacuole (PV). Upon infection, the cytokine interferon gamma (IFNγ) is produced and elicits host defence mechanisms able to recognise the PV and destroy the parasite. Hereby, Guanylate binding proteins, ubiquitin and the E3 ubiquitin ligases Tripartite Motif Containing 21 (TRIM21) and TNF receptor associated factor 6 are targeted to the murine PV leading to its destruction. This study is the side product of research aiming to identify ubiquitinated substrates in a TRIM21-dependent fashion in murine cells infected with Toxoplasma.

RESULTS: We infected IFNγ-stimulated murine embryonic fibroblasts (MEFs) from either C57BL/6×129 wild-type (WT) mice or C57BL/6 TRIM21-/- mice with Toxoplasma. Using mass spectrometry, we analysed proteins in both cell backgrounds presenting with the di-glycine remnant of ubiquitination. In addition, we compared peptide levels between WT and TRIM21-/- cells. In line with earlier reports, Gbp1 was expressed to higher levels in the C57BL/6×129 WT MEFs compared to the C57BL/6-only background TRIM21-/- MEFs. Protein expression differences in these different murine backgrounds thus precluded identification of TRIM21-dependent ubiquitinated substrates. Nevertheless, we identified and confirmed Gbp1 and Gbp2 as being ubiquitinated in a Toxoplasma-infection independent manner.}, } @article {pmid29510703, year = {2018}, author = {Barlow, LD and Nývltová, E and Aguilar, M and Tachezy, J and Dacks, JB}, title = {A sophisticated, differentiated Golgi in the ancestor of eukaryotes.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {27}, pmid = {29510703}, issn = {1741-7007}, support = {R21 ES021028/ES/NIEHS NIH HHS/United States ; }, abstract = {BACKGROUND: The Golgi apparatus is a central meeting point for the endocytic and exocytic systems in eukaryotic cells, and the organelle's dysfunction results in human disease. Its characteristic morphology of multiple differentiated compartments organized into stacked flattened cisternae is one of the most recognizable features of modern eukaryotic cells, and yet how this is maintained is not well understood. The Golgi is also an ancient aspect of eukaryotes, but the extent and nature of its complexity in the ancestor of eukaryotes is unclear. Various proteins have roles in organizing the Golgi, chief among them being the golgins.

RESULTS: We address Golgi evolution by analyzing genome sequences from organisms which have lost stacked cisternae as a feature of their Golgi and those that have not. Using genomics and immunomicroscopy, we first identify Golgi in the anaerobic amoeba Mastigamoeba balamuthi. We then searched 87 genomes spanning eukaryotic diversity for presence of the most prominent proteins implicated in Golgi structure, focusing on golgins. We show some candidates as animal specific and others as ancestral to eukaryotes.

CONCLUSIONS: None of the proteins examined show a phyletic distribution that correlates with the morphology of stacked cisternae, suggesting the possibility of stacking as an emergent property. Strikingly, however, the combination of golgins conserved among diverse eukaryotes allows for the most detailed reconstruction of the organelle to date, showing a sophisticated Golgi with differentiated compartments and trafficking pathways in the common eukaryotic ancestor.}, } @article {pmid29510700, year = {2018}, author = {Tajadura-Ortega, V and Garg, R and Allen, R and Owczarek, C and Bright, MD and Kean, S and Mohd-Noor, A and Grigoriadis, A and Elston, TC and Hahn, KM and Ridley, AJ}, title = {An RNAi screen of Rho signalling networks identifies RhoH as a regulator of Rac1 in prostate cancer cell migration.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {29}, pmid = {29510700}, issn = {1741-7007}, support = {C6620/A15961//Cancer Research UK/United Kingdom ; U01-EB018816/NH/NIH HHS/United States ; P01 GM103723/GM/NIGMS NIH HHS/United States ; R01-GM079271/NH/NIH HHS/United States ; R35 GM122596/GM/NIGMS NIH HHS/United States ; PO1-GM103723/NH/NIH HHS/United States ; C41786/A132//Cancer Research UK/United Kingdom ; C6220/A8833//Cancer Research UK/United Kingdom ; }, abstract = {BACKGROUND: Cell migration is essential for development and tissue repair, but it also contributes to disease. Rho GTPases regulate cell migration, but a comprehensive analysis of how each Rho signalling component affects migration has not been carried out.

RESULTS: Through an RNA interference screen, and using a prostate cancer cell line, we find that approximately 25% of Rho network components alter migration. Some genes enhance migration while others decrease basal and/or hepatocyte growth factor-stimulated migration. Surprisingly, we identify RhoH as a screen hit. RhoH expression is normally restricted to haematopoietic cells, but we find it is expressed in multiple epithelial cancer cell lines. High RhoH expression in samples from prostate cancer patients correlates with earlier relapse. RhoH depletion reduces cell speed and persistence and decreases migratory polarity. Rac1 activity normally localizes to the front of migrating cells at areas of dynamic membrane movement, but in RhoH-depleted cells active Rac1 is localised around the whole cell periphery and associated with membrane regions that are not extending or retracting. RhoH interacts with Rac1 and with several p21-activated kinases (PAKs), which are Rac effectors. Similar to RhoH depletion, PAK2 depletion increases cell spread area and reduces cell migration. In addition, RhoH depletion reduces lamellipodium extension induced by PAK2 overexpression.

CONCLUSIONS: We describe a novel role for RhoH in prostate cancer cell migration. We propose that RhoH promotes cell migration by coupling Rac1 activity and PAK2 to membrane protrusion. Our results also suggest that RhoH expression levels correlate with prostate cancer progression.}, } @article {pmid29510689, year = {2018}, author = {Ruan, S and Stormo, GD}, title = {Comparison of discriminative motif optimization using matrix and DNA shape-based models.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {86}, pmid = {29510689}, issn = {1471-2105}, support = {HG000249/HG/NHGRI NIH HHS/United States ; T32 HG000045/HG/NHGRI NIH HHS/United States ; }, mesh = {*Algorithms ; Area Under Curve ; Binding Sites ; DNA/*chemistry ; Databases, Nucleic Acid ; Humans ; *Models, Molecular ; Nucleotide Motifs/*genetics ; *Position-Specific Scoring Matrices ; Protein Binding ; }, abstract = {BACKGROUND: Transcription factor (TF) binding site specificity is commonly represented by some form of matrix model in which the positions in the binding site are assumed to contribute independently to the site's activity. The independence assumption is known to be an approximation, often a good one but sometimes poor. Alternative approaches have been developed that use k-mers (DNA "words" of length k) to account for the non-independence, and more recently DNA structural parameters have been incorporated into the models. ChIP-seq data are often used to assess the discriminatory power of motifs and to compare different models. However, to measure the improvement due to using more complex models, one must compare to optimized matrix models.

RESULTS: We describe a program "Discriminative Additive Model Optimization" (DAMO) that uses positive and negative examples, as in ChIP-seq data, and finds the additive position weight matrix (PWM) that maximizes the Area Under the Receiver Operating Characteristic Curve (AUROC). We compare to a recent study where structural parameters, serving as features in a gradient boosting classifier algorithm, are shown to improve the AUROC over JASPAR position frequency matrices (PFMs). In agreement with the previous results, we find that adding structural parameters gives the largest improvement, but most of the gain can be obtained by an optimized PWM and nearly all of the gain can be obtained with a di-nucleotide extension to the PWM.

CONCLUSION: To appropriately compare different models for TF bind sites, optimized models must be used. PWMs and their extensions are good representations of binding specificity for most TFs, and more complex models, including the incorporation of DNA shape features and gradient boosting classifiers, provide only moderate improvements for a few TFs.}, } @article {pmid29510677, year = {2018}, author = {Pine, PS and Lund, SP and Parsons, JR and Vang, LK and Mahabal, AA and Cinquini, L and Kelly, SC and Kincaid, H and Crichton, DJ and Spira, A and Liu, G and Gower, AC and Pass, HI and Goparaju, C and Dubinett, SM and Krysan, K and Stass, SA and Kukuruga, D and Van Keuren-Jensen, K and Courtright-Lim, A and Thompson, KL and Rosenzweig, BA and Sorbara, L and Srivastava, S and Salit, ML}, title = {Summarizing performance for genome scale measurement of miRNA: reference samples and metrics.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {180}, pmid = {29510677}, issn = {1471-2164}, support = {U01CA214182//Division of Cancer Prevention, National Cancer Institute/International ; U01CA214182//Division of Cancer Prevention, National Cancer Institute/International ; U01CA214195//Division of Cancer Prevention, National Cancer Institute/International ; U24CA115091//Division of Cancer Prevention, National Cancer Institute/International ; }, mesh = {Brain/*metabolism ; Female ; Gene Expression Profiling/methods/*standards ; *Genome, Human ; High-Throughput Nucleotide Sequencing/methods ; Humans ; Liver/*metabolism ; MicroRNAs/*genetics ; Placenta/*metabolism ; Pregnancy ; Reference Standards ; }, abstract = {BACKGROUND: The potential utility of microRNA as biomarkers for early detection of cancer and other diseases is being investigated with genome-scale profiling of differentially expressed microRNA. Processes for measurement assurance are critical components of genome-scale measurements. Here, we evaluated the utility of a set of total RNA samples, designed with between-sample differences in the relative abundance of miRNAs, as process controls.

RESULTS: Three pure total human RNA samples (brain, liver, and placenta) and two different mixtures of these components were evaluated as measurement assurance control samples on multiple measurement systems at multiple sites and over multiple rounds. In silico modeling of mixtures provided benchmark values for comparison with physical mixtures. Biomarker development laboratories using next-generation sequencing (NGS) or genome-scale hybridization assays participated in the study and returned data from the samples using their routine workflows. Multiplexed and single assay reverse-transcription PCR (RT-PCR) was used to confirm in silico predicted sample differences. Data visualizations and summary metrics for genome-scale miRNA profiling assessment were developed using this dataset, and a range of performance was observed. These metrics have been incorporated into an online data analysis pipeline and provide a convenient dashboard view of results from experiments following the described design. The website also serves as a repository for the accumulation of performance values providing new participants in the project an opportunity to learn what may be achievable with similar measurement processes.

CONCLUSIONS: The set of reference samples used in this study provides benchmark values suitable for assessing genome-scale miRNA profiling processes. Incorporation of these metrics into an online resource allows laboratories to periodically evaluate their performance and assess any changes introduced into their measurement process.}, } @article {pmid29510674, year = {2018}, author = {Jin, Y and Wo, Y and Tong, H and Song, S and Zhang, L and Brown, RP}, title = {Evolutionary analysis of mitochondrially encoded proteins of toad-headed lizards, Phrynocephalus, along an altitudinal gradient.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {185}, pmid = {29510674}, issn = {1471-2164}, support = {31372183//National Natural Science Foundation of China/International ; 31772447//National Natural Science Foundation of China/International ; }, mesh = {*Altitude ; Animals ; DNA, Mitochondrial/genetics ; *Evolution, Molecular ; Genome, Mitochondrial ; Lizards/*genetics ; Mitochondrial Proteins/*genetics ; Open Reading Frames ; Phylogeny ; Protein Subunits ; }, abstract = {BACKGROUND: Animals living at high altitude must adapt to environments with hypoxia and low temperatures, but relatively little is known about underlying genetic changes. Toad-headed lizards of the genus Phrynocephalus cover a broad altitudinal gradient of over 4000 m and are useful models for studies of such adaptive responses. In one of the first studies to have considered selection on mitochondrial protein-coding regions in an ectothermic group distributed over such a wide range of environments, we analysed nineteen complete mitochondrial genomes from all Chinese Phrynocephalus (including eight genomes sequenced for the first time). Initial analyses used site and branch-site model (program: PAML) approaches to examine nonsynonymous: synonymous substitution rates across the mtDNA tree.

RESULTS: Ten positively selected sites were discovered, nine of which corresponded to subunits ND2, ND3, ND4, ND5, and ND6 within the respiratory chain enzyme mitochondrial Complex I (NADH Coenzyme Q oxidoreductase). Four of these sites showed evidence of general long-term selection across the group while the remainder showed evidence of episodic selection across different branches of the tree. Some of these branches corresponded to increases in altitude and/or latitude. Analyses of physicochemical changes in protein structures revealed that residue changes at sites that were under selection corresponded to major functional differences. Analyses of coevolution point to coevolution of selected sites within the ND4 subunit, with key sites associated with proton translocation across the mitochondrial membrane.

CONCLUSIONS: Our results identify mitochondrial Complex I as a target for environment-mediated selection in this group of lizards, a complex that frequently appears to be under selection in other organisms. This makes these lizards good candidates for more detailed future studies of molecular evolution.}, } @article {pmid29510672, year = {2018}, author = {Tokan, V and Puterova, J and Lexa, M and Kejnovsky, E}, title = {Quadruplex DNA in long terminal repeats in maize LTR retrotransposons inhibits the expression of a reporter gene in yeast.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {184}, pmid = {29510672}, issn = {1471-2164}, support = {18-00258S//Grantová Agentura České Republiky/International ; FIT-S-17-3964//Vysoké Učení Technické v Brně/International ; }, mesh = {*G-Quadruplexes ; *Genes, Reporter ; *Genome, Plant ; High-Throughput Nucleotide Sequencing ; *Retroelements ; Saccharomyces cerevisiae/*genetics/growth & development ; *Terminal Repeat Sequences ; Transcription, Genetic ; Zea mays/*genetics/growth & development/metabolism ; }, abstract = {BACKGROUND: Many studies have shown that guanine-rich DNA sequences form quadruplex structures (G4) in vitro but there is scarce evidence of guanine quadruplexes in vivo. The majority of potential quadruplex-forming sequences (PQS) are located in transposable elements (TEs), especially close to promoters within long terminal repeats of plant LTR retrotransposons.

RESULTS: In order to test the potential effect of G4s on retrotransposon expression, we cloned the long terminal repeats of selected maize LTR retrotransposons upstream of the lacZ reporter gene and measured its transcription and translation in yeast. We found that G4s had an inhibitory effect on translation in vivo since "mutants" (where guanines were replaced by adenines in PQS) showed higher expression levels than wild-types. In parallel, we confirmed by circular dichroism measurements that the selected sequences can indeed adopt G4 conformation in vitro. Analysis of RNA-Seq of polyA RNA in maize seedlings grown in the presence of a G4-stabilizing ligand (NMM) showed both inhibitory as well as stimulatory effects on the transcription of LTR retrotransposons.

CONCLUSIONS: Our results demonstrate that quadruplex DNA located within long terminal repeats of LTR retrotransposons can be formed in vivo and that it plays a regulatory role in the LTR retrotransposon life-cycle, thus also affecting genome dynamics.}, } @article {pmid29510668, year = {2018}, author = {Dos Santos Vasconcelos, CR and de Lima Campos, T and Rezende, AM}, title = {Building protein-protein interaction networks for Leishmania species through protein structural information.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {85}, pmid = {29510668}, issn = {1471-2105}, support = {478138/2013-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; Studentship//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/International ; }, mesh = {Area Under Curve ; Leishmania/*metabolism ; Leishmaniasis/metabolism/parasitology ; Machine Learning ; *Protein Interaction Maps ; Proteome/metabolism ; Protozoan Proteins/*chemistry ; Thermodynamics ; }, abstract = {BACKGROUND: Systematic analysis of a parasite interactome is a key approach to understand different biological processes. It makes possible to elucidate disease mechanisms, to predict protein functions and to select promising targets for drug development. Currently, several approaches for protein interaction prediction for non-model species incorporate only small fractions of the entire proteomes and their interactions. Based on this perspective, this study presents an integration of computational methodologies, protein network predictions and comparative analysis of the protozoan species Leishmania braziliensis and Leishmania infantum. These parasites cause Leishmaniasis, a worldwide distributed and neglected disease, with limited treatment options using currently available drugs.

RESULTS: The predicted interactions were obtained from a meta-approach, applying rigid body docking tests and template-based docking on protein structures predicted by different comparative modeling techniques. In addition, we trained a machine-learning algorithm (Gradient Boosting) using docking information performed on a curated set of positive and negative protein interaction data. Our final model obtained an AUC = 0.88, with recall = 0.69, specificity = 0.88 and precision = 0.83. Using this approach, it was possible to confidently predict 681 protein structures and 6198 protein interactions for L. braziliensis, and 708 protein structures and 7391 protein interactions for L. infantum. The predicted networks were integrated to protein interaction data already available, analyzed using several topological features and used to classify proteins as essential for network stability.

CONCLUSIONS: The present study allowed to demonstrate the importance of integrating different methodologies of interaction prediction to increase the coverage of the protein interaction of the studied protocols, besides it made available protein structures and interactions not previously reported.}, } @article {pmid29510665, year = {2018}, author = {Sugiaman-Trapman, D and Vitezic, M and Jouhilahti, EM and Mathelier, A and Lauter, G and Misra, S and Daub, CO and Kere, J and Swoboda, P}, title = {Characterization of the human RFX transcription factor family by regulatory and target gene analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {181}, pmid = {29510665}, issn = {1471-2164}, support = {KID funding//Karolinska Institutet/International ; Distinguished Professor Award//Karolinska Institutet/International ; Strategic Neurosciences Program//Karolinska Institutet/International ; EU Horizon 2020 Marie Curie Individual Fellowship//Horizon 2020/International ; 174CDE//Genome Canada Large Scale Applied Research Grant/International ; }, mesh = {DNA-Binding Proteins/genetics/metabolism ; *Gene Expression Regulation ; *Genome, Human ; Humans ; *Promoter Regions, Genetic ; Regulatory Factor X Transcription Factors/*genetics ; *Regulatory Sequences, Nucleic Acid ; Transcription Initiation Site ; }, abstract = {BACKGROUND: Evolutionarily conserved RFX transcription factors (TFs) regulate their target genes through a DNA sequence motif called the X-box. Thereby they regulate cellular specialization and terminal differentiation. Here, we provide a comprehensive analysis of all the eight human RFX genes (RFX1-8), their spatial and temporal expression profiles, potential upstream regulators and target genes.

RESULTS: We extracted all known human RFX1-8 gene expression profiles from the FANTOM5 database derived from transcription start site (TSS) activity as captured by Cap Analysis of Gene Expression (CAGE) technology. RFX genes are broadly (RFX1-3, RFX5, RFX7) and specifically (RFX4, RFX6) expressed in different cell types, with high expression in four organ systems: immune system, gastrointestinal tract, reproductive system and nervous system. Tissue type specific expression profiles link defined RFX family members with the target gene batteries they regulate. We experimentally confirmed novel TSS locations and characterized the previously undescribed RFX8 to be lowly expressed. RFX tissue and cell type specificity arises mainly from differences in TSS architecture. RFX transcript isoforms lacking a DNA binding domain (DBD) open up new possibilities for combinatorial target gene regulation. Our results favor a new grouping of the RFX family based on protein domain composition. We uncovered and experimentally confirmed the TFs SP2 and ESR1 as upstream regulators of specific RFX genes. Using TF binding profiles from the JASPAR database, we determined relevant patterns of X-box motif positioning with respect to gene TSS locations of human RFX target genes.

CONCLUSIONS: The wealth of data we provide will serve as the basis for precisely determining the roles RFX TFs play in human development and disease.}, } @article {pmid29510662, year = {2018}, author = {Dagnall, CL and Morton, LM and Hicks, BD and Li, S and Zhou, W and Karlins, E and Teshome, K and Chowdhury, S and Lashley, KS and Sampson, JN and Robison, LL and Armstrong, GT and Bhatia, S and Radloff, GA and Davies, SM and Tucker, MA and Yeager, M and Chanock, SJ}, title = {Successful use of whole genome amplified DNA from multiple source types for high-density Illumina SNP microarrays.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {182}, pmid = {29510662}, issn = {1471-2164}, support = {U24 CA055727/CA/NCI NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {DNA/analysis/blood/*genetics ; *Genome, Human ; Genomics ; Genotype ; Humans ; Mouth Mucosa/*metabolism ; Neoplasms/blood/*genetics ; Nucleic Acid Amplification Techniques ; Oligonucleotide Array Sequence Analysis/methods ; *Polymorphism, Single Nucleotide ; Saliva/*metabolism ; }, abstract = {BACKGROUND: The recommended genomic DNA input requirements for whole genome single nucleotide polymorphism microarrays can limit the scope of molecular epidemiological studies. We performed a large-scale evaluation of whole genome amplified DNA as input into high-density, whole-genome Illumina® Infinium® SNP microarray.

RESULTS: Overall, 6622 DNA samples from 5970 individuals were obtained from three distinct biospecimen sources and genotyped using gDNA and/or wgaDNA inputs. When genotypes from the same individual were compared with standard, native gDNA input amount, we observed 99.94% mean concordance with wgaDNA input.

CONCLUSIONS: Our results demonstrate that carefully conducted studies with wgaDNA inputs can yield high-quality genotyping results. These findings should enable investigators to consider expansion of ongoing studies using high-density SNP microarrays, currently challenged by small amounts of available DNA.}, } @article {pmid29510661, year = {2018}, author = {Wang, L and Jiang, Z and Huang, D and Duan, J and Huang, C and Sullivan, S and Vali, K and Yin, Y and Zhang, M and Wegrzyn, J and Tian, XC and Tang, Y}, title = {JAK/STAT3 regulated global gene expression dynamics during late-stage reprogramming process.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {183}, pmid = {29510661}, issn = {1471-2164}, support = {2016-67016-24894//National Institute of Food and Agriculture/International ; USDA W2171 regional project//National Institute of Food and Agriculture/International ; 58-8042-5-047//USDA-ARS/International ; }, mesh = {Animals ; Cells, Cultured ; *Cellular Reprogramming ; DNA Demethylation ; *Epigenesis, Genetic ; Epithelial-Mesenchymal Transition ; Gene Expression Profiling ; *Gene Expression Regulation ; Induced Pluripotent Stem Cells/*cytology ; Janus Kinase 1/genetics ; Meiosis ; Mice ; STAT3 Transcription Factor/genetics ; }, abstract = {BACKGROUND: The generation of induced pluripotent stem cells (iPSCs) has underdefined mechanisms. In addition, leukemia inhibitory factor (LIF) activated Janus kinase/signal transducer and activator of transcription 3 (JAK/STAT3) pathway is the master regulator for naïve-state pluripotency achievement and maintenance. However, the regulatory process to attain naïve pluripotent iPSCs is not well understood.

RESULTS: We performed transcriptome analysis to dissect the genomic expression during mouse iPSC induction, with or without blocking the JAK/STAT3 activity. We describe JAK/STAT3 signaling-specific biological events such as gametogenesis, meiotic/mitotic cell cycle, and DNA repair, and JAK/STAT3-dependent expression of key transcription factors such as the naïve pluripotency-specific genes, developmental pluripotency associated (Dppa) family, along with histone modifiers and non-coding RNAs in reprogramming. We discover that JAK/STAT3 activity does not affect early phase mesenchymal to epithelial transition (MET) but is necessary for proper imprinting of the Dlk1-Dio3 region, an essential event for pluripotency achievement at late-reprogramming stage. This correlates with the JAK/STAT3-dependent stimulation of Dppa3 and Polycomb repressive complex 2 (PRC2) genes. We further demonstrate that JAK/STAT3 activity is essential for DNA demethylation of pluripotent loci including Oct4, Nanog, and the Dlk1-Dio3 regions. These findings correlate well with the previously identified STAT3 direct targets. We further propose a model of pluripotency achievement regulated by JAK/STAT3 signaling during the reprogramming process.

CONCLUSIONS: Our study illustrates novel insights for JAK/STAT3 promoted pluripotency establishment, which are valuable for further improving the naïve-pluripotent iPSC generation across different species including humans.}, } @article {pmid29510660, year = {2018}, author = {Lie, KK and Tørresen, OK and Solbakken, MH and Rønnestad, I and Tooming-Klunderud, A and Nederbragt, AJ and Jentoft, S and Sæle, Ø}, title = {Loss of stomach, loss of appetite? Sequencing of the ballan wrasse (Labrus bergylta) genome and intestinal transcriptomic profiling illuminate the evolution of loss of stomach function in fish.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {186}, pmid = {29510660}, issn = {1471-2164}, support = {900554//Fiskeri- og Havbruksnæringens Forskningsfond/International ; 901135//Fiskeri- og Havbruksnæringens Forskningsfond (NO)/International ; }, mesh = {Animals ; Appetite ; *Biological Evolution ; Digestion ; Gastrointestinal Tract ; *Gene Expression Profiling ; Genome ; Perciformes/*genetics/physiology ; Phylogeny ; Stomach/*physiology ; }, abstract = {BACKGROUND: The ballan wrasse (Labrus bergylta) belongs to a large teleost family containing more than 600 species showing several unique evolutionary traits such as lack of stomach and hermaphroditism. Agastric fish are found throughout the teleost phylogeny, in quite diverse and unrelated lineages, indicating stomach loss has occurred independently multiple times in the course of evolution. By assembling the ballan wrasse genome and transcriptome we aimed to determine the genetic basis for its digestive system function and appetite regulation. Among other, this knowledge will aid the formulation of aquaculture diets that meet the nutritional needs of agastric species.

RESULTS: Long and short read sequencing technologies were combined to generate a ballan wrasse genome of 805 Mbp. Analysis of the genome and transcriptome assemblies confirmed the absence of genes that code for proteins involved in gastric function. The gene coding for the appetite stimulating protein ghrelin was also absent in wrasse. Gene synteny mapping identified several appetite-controlling genes and their paralogs previously undescribed in fish. Transcriptome profiling along the length of the intestine found a declining expression gradient from the anterior to the posterior, and a distinct expression profile in the hind gut.

CONCLUSIONS: We showed gene loss has occurred for all known genes related to stomach function in the ballan wrasse, while the remaining functions of the digestive tract appear intact. The results also show appetite control in ballan wrasse has undergone substantial changes. The loss of ghrelin suggests that other genes, such as motilin, may play a ghrelin like role. The wrasse genome offers novel insight in to the evolutionary traits of this large family. As the stomach plays a major role in protein digestion, the lack of genes related to stomach digestion in wrasse suggests it requires formulated diets with higher levels of readily digestible protein than those for gastric species.}, } @article {pmid29510468, year = {2018}, author = {Weaver, TD and Gunz, P}, title = {Using geometric morphometric visualizations of directional selection gradients to investigate morphological differentiation.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {838-850}, doi = {10.1111/evo.13460}, pmid = {29510468}, issn = {1558-5646}, abstract = {Researchers studying extant and extinct taxa are often interested in identifying the evolutionary processes that have lead to the morphological differences among the taxa. Ideally, one could distinguish the influences of neutral evolutionary processes (genetic drift, mutation) from natural selection, and in situations for which selection is implicated, identify the targets of selection. The directional selection gradient is an effective tool for investigating evolutionary process, because it can relate form (size and shape) differences between taxa to the variation and covariation found within taxa. However, although most modern morphometric analyses use the tools of geometric morphometrics (GM) to analyze landmark data, to date, selection gradients have mainly been calculated from linear measurements. To address this methodological gap, here we present a GM approach for visualizing and comparing between-taxon selection gradients with each other, associated difference vectors, and "selection" gradients from neutral simulations. To exemplify our approach, we use a dataset of 347 three-dimensional landmarks and semilandmarks recorded on the crania of 260 primate specimens (112 humans, 67 common chimpanzees, 36 bonobos, 45 gorillas). Results on this example dataset show how incorporating geometric information can provide important insights into the evolution of the human braincase, and serve to demonstrate the utility of our approach for understanding morphological evolution.}, } @article {pmid29510374, year = {2018}, author = {Choi, SS and Katsuyama, Y and Bai, L and Deng, Z and Ohnishi, Y and Kim, ES}, title = {Genome engineering for microbial natural product discovery.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {53-60}, doi = {10.1016/j.mib.2018.02.007}, pmid = {29510374}, issn = {1879-0364}, abstract = {The discovery and development of microbial natural products (MNPs) have played pivotal roles in the fields of human medicine and its related biotechnology sectors over the past several decades. The post-genomic era has witnessed the development of microbial genome mining approaches to isolate previously unsuspected MNP biosynthetic gene clusters (BGCs) hidden in the genome, followed by various BGC awakening techniques to visualize compound production. Additional microbial genome engineering techniques have allowed higher MNP production titers, which could complement a traditional culture-based MNP chasing approach. Here, we describe recent developments in the MNP research paradigm, including microbial genome mining, NP BGC activation, and NP overproducing cell factory design.}, } @article {pmid29510236, year = {2018}, author = {Zheng, BY and Cao, LJ and Tang, P and van Achterberg, K and Hoffmann, AA and Chen, HY and Chen, XX and Wei, SJ}, title = {Gene arrangement and sequence of mitochondrial genomes yield insights into the phylogeny and evolution of bees and sphecid wasps (Hymenoptera: Apoidea).}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {1-9}, doi = {10.1016/j.ympev.2018.02.028}, pmid = {29510236}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Bees/*genetics ; *Gene Order ; Gene Rearrangement ; *Genome, Mitochondrial ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; Wasps/*genetics ; }, abstract = {The Apoidea represent a large and common superfamily of the Hymenoptera including the bees and sphecid wasps. A robust phylogenetic tree is essential to understanding the diversity, taxonomy and evolution of the Apoidea. In this study, features of apoid mitochondrial genomes were used to reconstruct phylogenetic relationships. Twelve apoid mitochondrial genomes were newly sequenced, representing six families and nine subfamilies. Gene rearrangement events have occurred in all apoid mitochondrial genomes sequenced to date. Sphecid wasps have both tRNA and protein-coding gene rearrangements in 5 of 8 species. In bees, the only rearranged genes are tRNAs; long-tongued bees (Apidae + Megachilidae) are characterized by movement of trnA to the trnI-trnQ-trnM tRNA cluster. Phylogenetic analyses of mitochondrial gene sequences support the known paraphyly of sphecid wasps, with bees nested within this clade. The Ampulicidae is sister to the remaining Apoidea. Crabronidae is paraphyletic, split into Crabronidae s.s. and Philanthidae, with the latter group a sister clade to bees. The monophyletic bees are either classified into two clades, long-tongued bees (Apidae + Megachilidae) and short-tongued bees (Andrenidae + Halictidae + Colletidae + Melitidae), or three groups with the Melitidae sister to the other bees. Our study showed that both gene sequences and arrangements provide information on the phylogeny of apoid families.}, } @article {pmid29510119, year = {2018}, author = {Stoller, ML and Roman, O and Deans, MR}, title = {Domineering non-autonomy in Vangl1;Vangl2 double mutants demonstrates intercellular PCP signaling in the vertebrate inner ear.}, journal = {Developmental biology}, volume = {437}, number = {1}, pages = {17-26}, pmid = {29510119}, issn = {1095-564X}, support = {R01 DC013066/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Carrier Proteins/*genetics/metabolism ; Cell Polarity/*genetics/physiology ; Ear, Inner/*metabolism ; Fluorescent Antibody Technique ; Homeodomain Proteins/metabolism ; Membrane Proteins/*genetics/metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/*genetics/metabolism ; Signal Transduction ; Transcription Factors/metabolism ; Vertebrates/metabolism ; }, abstract = {The organization of polarized stereociliary bundles is critical for the function of the inner ear sensory receptor hair cells that detect sound and motion, and these cells present a striking example of Planar Cell Polarity (PCP); the coordinated orientation of polarized structures within the plane of an epithelium. PCP is best understood in Drosophila where the essential genes regulating PCP were first discovered, and functions for the core PCP proteins encoded by these genes have been deciphered through phenotypic analysis of core PCP gene mutants. One illuminating phenotype is the domineering non-autonomy that is observed where abrupt disruptions in PCP signaling impacts the orientation of neighboring wild type cells, because this demonstrates local intercellular signaling mediated by the core PCP proteins. Using Emx2-Cre to generate an analogous mutant boundary in the mouse inner ear, we disrupted vertebrate PCP signaling in Vangl1;Vangl2 conditional knockouts. Due to unique aspects of vestibular anatomy, core PCP protein distribution along the mutant boundary generated in the utricle resembles the proximal side of vang mutant clones in the Drosophila wing, while the boundary in the saccule resembles and the distal side. Consistent with these protein distributions, a domineering non-autonomy phenotype occurs along the Emx2-Cre boundary in the mutant utricle that does not occur in the saccule. These results further support the hypothesis that core PCP function is conserved in vertebrates by demonstrating intercellular PCP signaling in the sensory epithelia of the mouse ear.}, } @article {pmid29509135, year = {2018}, author = {Song, J and Lim, Y and Joung, Y and Cho, JC and Kogure, K}, title = {Rubritalea profundi sp. nov., isolated from deep-seawater and emended description of the genus Rubritalea in the phylum Verrucomicrobia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002686}, pmid = {29509135}, issn = {1466-5034}, abstract = {A Gram-stain-negative, short-rod, facultatively anaerobic, non-motile and red-pigmented bacterium, designated SAORIC-165T, was isolated from a deep-seawater sample collected from the Pacific Ocean. The 16S rRNA gene sequence analysis showed that strain SAORIC-165T was most closely related to Rubritalea marina Pol012T (95.7 % sequence similarity) and formed a robust phylogenetic clade with other species of the genus Rubritalea in the phylum Verrucomicrobia. Optimal growth of strain SAORIC-165T was observed at 10 °C, pH 7.0 and in the presence of 2.0-3.5 % (w/v) NaCl. The DNA G+C content of strain SAORIC-165T was 50.7 mol% and MK-9 was the predominant isoprenoid quinone. The major cellular fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C14 : 0, anteiso-C15 : 0, C16 : 0 and C14 : 0. The major polar lipids constituted phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol and unidentified phospholipids and aminolipids. On the basis of the taxonomic data obtained in this study, it was concluded that strain SAORIC-165T represented a novel species of the genus Rubritalea, for which the name Rubritalea profundi sp. nov. is proposed. The type strain of Rubritalea profundi is SAORIC-165T (=NBRC 110691T=KCTC 52460T).}, } @article {pmid29509133, year = {2018}, author = {Dai, H and Wang, Y and Fang, Y and Huang, Z and Kan, B and Wang, D}, title = {Proteus alimentorum sp. nov., isolated from pork and lobster in Ma'anshan city, China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1390-1395}, doi = {10.1099/ijsem.0.002689}, pmid = {29509133}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nephropidae ; Nucleic Acid Hybridization ; *Phylogeny ; Proteus/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Red Meat/*microbiology ; Seafood/*microbiology ; Sequence Analysis, DNA ; Swine ; }, abstract = {Two strains of Gram-stain-negative, facultatively anaerobic short-rod bacteria were recovered from two different food samples in Ma'anshan city, Anhui province, China in 2008. The bacteria were characterized in a polyphasic taxonomic study that included phenotypic, phylogenetic and genotypic methodologies. Phylogenetic analysis of the 16S rRNA gene demonstrated that the two strains belonged to the genus Proteus and were most similar to Proteus vulgaris ATCC 29905T with a score of 99.7 %. Phylogenetic analysis of the rpoB gene placed the two strains into a cluster with a distinctly interspecies phylogenetic branch that was clearly separated from six type strains of the genus Proteus, with the most closely related species being Proteus mirabilis ATCC 29906T. In silico genomic comparisons, including in silico DNA-DNA hybridization (isDDH) and average nucleotide identity (ANI) analysis showed that the representative strain, 08MAS0041T, and all six Proteus species share less than 70 % isDDH and have a 95 % ANI cutoff level, supporting the designation of the two strains as a novel species of the genus Proteus. The predominant cellular fatty acids of strain 08MAS0041T were C16 : 0 (24.8 %), C16 : 1ω7c/16 : 1ω6c (16.5 %), C18 : 1ω6c/C18 : 1ω7c (14.5 %), C17 : 0 cyclo (12.6 %) and C16 : 1iso I/C14 : 0 3-OH (10.6 %). The analysis of biochemical, phylogenetic and genomic data confirmed that the two strains were clearly different from all recognized species of the genus Proteus and represent a novel Proteus species, for which the name Proteus alimentorum sp. nov. is proposed. The type strain is 08MAS0041T (=DSM 104685T=CGMCC 1.15939T).}, } @article {pmid29509131, year = {2018}, author = {Chen, SC and Huang, HH and Lai, MC and Weng, CY and Chiu, HH and Tang, SL and Rogozin, DY and Degermendzhy, AG}, title = {Methanolobus psychrotolerans sp. nov., a psychrotolerant methanoarchaeon isolated from a saline meromictic lake in Siberia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1378-1383}, doi = {10.1099/ijsem.0.002685}, pmid = {29509131}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Lakes/*microbiology ; Methanosarcinaceae/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; Siberia ; }, abstract = {A psychrotolerant, methylotrophic methanogen, strain YSF-03T, was isolated from the saline meromictic Lake Shira in Siberia. Cells of strain YSF-03T were non-motile, irregular cocci and 0.8-1.2 µm in diameter. The methanogenic substrates utilized by strain YSF-03T were methanol and trimethylamine. The temperature range of growth for strain YSF-03T was from 0 to 37 °C. The optimum growth conditions were 30-37 °C, pH 7.0-7.4 and 0.17 M NaCl. The G+C content of the genome of strain YSF-03T was 41.3 mol%. Phylogenetic analysis revealed that strain YSF-03T was most closely related to Methanolobus profundi MobMT (98.15 % similarity in 16S rRNA gene sequence). Genome relatedness between strain YSF-03T and MobMT was computed using the Genome-to-Genome Distance Calculator and average nucleotide identity, which gave values of 23.5 and 79.3 %, respectively. Based on the morphological, phenotypic, phylogenetic and genomic relatedness data presented here, it is evident that strain YSF-03T represents a novel species of the genus Methanolobus, for which the name Methanolobus psychrotolerans sp. nov. is proposed. The type strain is YSF-03T (=BCRC AR10049T=DSM 104044T=NBRC 112514T).}, } @article {pmid29507425, year = {2018}, author = {Goldmann, JM and Seplyarskiy, VB and Wong, WSW and Vilboux, T and Neerincx, PB and Bodian, DL and Solomon, BD and Veltman, JA and Deeken, JF and Gilissen, C and Niederhuber, JE}, title = {Germline de novo mutation clusters arise during oocyte aging in genomic regions with high double-strand-break incidence.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {487-492}, doi = {10.1038/s41588-018-0071-6}, pmid = {29507425}, issn = {1546-1718}, abstract = {Clustering of mutations has been observed in cancer genomes as well as for germline de novo mutations (DNMs). We identified 1,796 clustered DNMs (cDNMs) within whole-genome-sequencing data from 1,291 parent-offspring trios to investigate their patterns and infer a mutational mechanism. We found that the number of clusters on the maternal allele was positively correlated with maternal age and that these clusters consisted of more individual mutations with larger intermutational distances than those of paternal clusters. More than 50% of maternal clusters were located on chromosomes 8, 9 and 16, in previously identified regions with accelerated maternal mutation rates. Maternal clusters in these regions showed a distinct mutation signature characterized by C>G transversions. Finally, we found that maternal clusters were associated with processes involving double-strand-breaks (DSBs), such as meiotic gene conversions and de novo deletion events. This result suggested accumulation of DSB-induced mutations throughout oocyte aging as the mechanism underlying the formation of maternal mutation clusters.}, } @article {pmid29507424, year = {2018}, author = {Kramer, NJ and Haney, MS and Morgens, DW and Jovičić, A and Couthouis, J and Li, A and Ousey, J and Ma, R and Bieri, G and Tsui, CK and Shi, Y and Hertz, NT and Tessier-Lavigne, M and Ichida, JK and Bassik, MC and Gitler, AD}, title = {CRISPR-Cas9 screens in human cells and primary neurons identify modifiers of C9ORF72 dipeptide-repeat-protein toxicity.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {603-612}, pmid = {29507424}, issn = {1546-1718}, support = {DP2 HD084069/HD/NICHD NIH HHS/United States ; P30 NS069375/NS/NINDS NIH HHS/United States ; R01 NS097850/NS/NINDS NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; T32 GM007790/GM/NIGMS NIH HHS/United States ; R35 NS097263/NS/NINDS NIH HHS/United States ; }, abstract = {Hexanucleotide-repeat expansions in the C9ORF72 gene are the most common cause of amyotrophic lateral sclerosis and frontotemporal dementia (c9ALS/FTD). The nucleotide-repeat expansions are translated into dipeptide-repeat (DPR) proteins, which are aggregation prone and may contribute to neurodegeneration. We used the CRISPR-Cas9 system to perform genome-wide gene-knockout screens for suppressors and enhancers of C9ORF72 DPR toxicity in human cells. We validated hits by performing secondary CRISPR-Cas9 screens in primary mouse neurons. We uncovered potent modifiers of DPR toxicity whose gene products function in nucleocytoplasmic transport, the endoplasmic reticulum (ER), proteasome, RNA-processing pathways, and chromatin modification. One modifier, TMX2, modulated the ER-stress signature elicited by C9ORF72 DPRs in neurons and improved survival of human induced motor neurons from patients with C9ORF72 ALS. Together, our results demonstrate the promise of CRISPR-Cas9 screens in defining mechanisms of neurodegenerative diseases.}, } @article {pmid29507423, year = {2018}, author = {Ishiura, H and Doi, K and Mitsui, J and Yoshimura, J and Matsukawa, MK and Fujiyama, A and Toyoshima, Y and Kakita, A and Takahashi, H and Suzuki, Y and Sugano, S and Qu, W and Ichikawa, K and Yurino, H and Higasa, K and Shibata, S and Mitsue, A and Tanaka, M and Ichikawa, Y and Takahashi, Y and Date, H and Matsukawa, T and Kanda, J and Nakamoto, FK and Higashihara, M and Abe, K and Koike, R and Sasagawa, M and Kuroha, Y and Hasegawa, N and Kanesawa, N and Kondo, T and Hitomi, T and Tada, M and Takano, H and Saito, Y and Sanpei, K and Onodera, O and Nishizawa, M and Nakamura, M and Yasuda, T and Sakiyama, Y and Otsuka, M and Ueki, A and Kaida, KI and Shimizu, J and Hanajima, R and Hayashi, T and Terao, Y and Inomata-Terada, S and Hamada, M and Shirota, Y and Kubota, A and Ugawa, Y and Koh, K and Takiyama, Y and Ohsawa-Yoshida, N and Ishiura, S and Yamasaki, R and Tamaoka, A and Akiyama, H and Otsuki, T and Sano, A and Ikeda, A and Goto, J and Morishita, S and Tsuji, S}, title = {Expansions of intronic TTTCA and TTTTA repeats in benign adult familial myoclonic epilepsy.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {581-590}, doi = {10.1038/s41588-018-0067-2}, pmid = {29507423}, issn = {1546-1718}, abstract = {Epilepsy is a common neurological disorder, and mutations in genes encoding ion channels or neurotransmitter receptors are frequent causes of monogenic forms of epilepsy. Here we show that abnormal expansions of TTTCA and TTTTA repeats in intron 4 of SAMD12 cause benign adult familial myoclonic epilepsy (BAFME). Single-molecule, real-time sequencing of BAC clones and nanopore sequencing of genomic DNA identified two repeat configurations in SAMD12. Intriguingly, in two families with a clinical diagnosis of BAFME in which no repeat expansions in SAMD12 were observed, we identified similar expansions of TTTCA and TTTTA repeats in introns of TNRC6A and RAPGEF2, indicating that expansions of the same repeat motifs are involved in the pathogenesis of BAFME regardless of the genes in which the expanded repeats are located. This discovery that expansions of noncoding repeats lead to neuronal dysfunction responsible for myoclonic tremor and epilepsy extends the understanding of diseases with such repeat expansion.}, } @article {pmid29507422, year = {2018}, author = {Hoffmann, TJ and Theusch, E and Haldar, T and Ranatunga, DK and Jorgenson, E and Medina, MW and Kvale, MN and Kwok, PY and Schaefer, C and Krauss, RM and Iribarren, C and Risch, N}, title = {A large electronic-health-record-based genome-wide study of serum lipids.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {401-413}, pmid = {29507422}, issn = {1546-1718}, support = {K01 DC013300/DC/NIDCD NIH HHS/United States ; P50 GM115318/GM/NIGMS NIH HHS/United States ; R21 AG046616/AG/NIA NIH HHS/United States ; RC2 AG036607/AG/NIA NIH HHS/United States ; }, abstract = {A genome-wide association study (GWAS) of 94,674 ancestrally diverse Kaiser Permanente members using 478,866 longitudinal electronic health record (EHR)-derived measurements for untreated serum lipid levels empowered multiple new findings: 121 new SNP associations (46 primary, 15 conditional, and 60 in meta-analysis with Global Lipids Genetic Consortium data); an increase of 33-42% in variance explained with multiple measurements; sex differences in genetic impact (greater impact in females for LDL, HDL, and total cholesterol and the opposite for triglycerides); differences in variance explained among non-Hispanic whites, Latinos, African Americans, and East Asians; genetic dominance and epistatic interaction, with strong evidence for both at the ABO and FUT2 genes for LDL; and tissue-specific enrichment of GWAS-associated SNPs among liver, adipose, and pancreas eQTLs. Using EHR pharmacy data, both LDL and triglyceride genetic risk scores (477 SNPs) were strongly predictive of age at initiation of lipid-lowering treatment. These findings highlight the value of longitudinal EHRs for identifying new genetic features of cholesterol and lipoprotein metabolism with implications for lipid treatment and risk of coronary heart disease.}, } @article {pmid29507381, year = {2018}, author = {Burns, JA and Pittis, AA and Kim, E}, title = {Publisher Correction: Gene-based predictive models of trophic modes suggest Asgard archaea are not phagocytotic.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {751}, doi = {10.1038/s41559-018-0520-8}, pmid = {29507381}, issn = {2397-334X}, abstract = {In the version of this Article originally published, question marks appeared in Table 1; they should have been tick marks. This has now been corrected in all versions of the Article.}, } @article {pmid29507380, year = {2018}, author = {Gaither, MR and Gkafas, GA and de Jong, M and Sarigol, F and Neat, F and Regnier, T and Moore, D and Grӧcke, DR and Hall, N and Liu, X and Kenny, J and Lucaci, A and Hughes, M and Haldenby, S and Hoelzel, AR}, title = {Genomics of habitat choice and adaptive evolution in a deep-sea fish.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {680-687}, doi = {10.1038/s41559-018-0482-x}, pmid = {29507380}, issn = {2397-334X}, abstract = {Intraspecific diversity promotes evolutionary change, and when partitioned among geographic regions or habitats can form the basis for speciation. Marine species live in an environment that can provide as much scope for diversification in the vertical as in the horizontal dimension. Understanding the relevant mechanisms will contribute significantly to our understanding of eco-evolutionary processes and effective biodiversity conservation. Here, we provide an annotated genome assembly for the deep-sea fish Coryphaenoides rupestris and re-sequencing data to show that differentiation at non-synonymous sites in functional loci distinguishes individuals living at different depths, independent of horizontal spatial distance. Our data indicate disruptive selection at these loci; however, we find no clear evidence for differentiation at neutral loci that may indicate assortative mating. We propose that individuals with distinct genotypes at relevant loci segregate by depth as they mature (supported by survey data), which may be associated with ecotype differentiation linked to distinct phenotypic requirements at different depths.}, } @article {pmid29507379, year = {2018}, author = {Thomsen, MS and Altieri, AH and Angelini, C and Bishop, MJ and Gribben, PE and Lear, G and He, Q and Schiel, DR and Silliman, BR and South, PM and Watson, DM and Wernberg, T and Zotz, G}, title = {Secondary foundation species enhance biodiversity.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {634-639}, doi = {10.1038/s41559-018-0487-5}, pmid = {29507379}, issn = {2397-334X}, abstract = {It has long been recognized that primary foundation species (FS), such as trees and seagrasses, enhance biodiversity. Among the species facilitated are secondary FS, including mistletoes and epiphytes. Case studies have demonstrated that secondary FS can further modify habitat-associated organisms ('inhabitants'), but their net effects remain unknown. Here we assess how inhabitants, globally, are affected by secondary FS. We extracted and calculated 2,187 abundance and 397 richness Hedges' g effect sizes from 91 and 50 publications, respectively. A weighted meta-analysis revealed that secondary FS significantly enhanced the abundance and richness of inhabitants compared to the primary FS alone. This indirect facilitation arising through sequential habitat formation was consistent across environmental and experimental conditions. Complementary unweighted analyses on log response ratios revealed that the magnitude of these effects was similar to the global average strength of direct facilitation from primary foundation species and greater than the average strength of trophic cascades, a widely recognized type of indirect facilitation arising through sequential consumption. The finding that secondary FS enhance the abundance and richness of inhabitants has important implications for understanding the mechanisms that regulate biodiversity. Integrating secondary FS into conservation practice will improve our ability to protect biodiversity and ecosystem function.}, } @article {pmid29507378, year = {2018}, author = {Reynolds, N}, title = {Cutting edge analyses.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {591-592}, doi = {10.1038/s41559-018-0511-9}, pmid = {29507378}, issn = {2397-334X}, } @article {pmid29507377, year = {2018}, author = {Režek, Ž and Dibble, HL and McPherron, SP and Braun, DR and Lin, SC}, title = {Two million years of flaking stone and the evolutionary efficiency of stone tool technology.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {628-633}, doi = {10.1038/s41559-018-0488-4}, pmid = {29507377}, issn = {2397-334X}, abstract = {Temporal variability in flaking stone has been used as one of the currencies for hominin behavioural and biological evolution. This variability is usually traced through changes in artefact forms and techniques of production, resulting overall in unilineal and normative models of hominin adaptation. Here, we focus on the fundamental purpose of flaking stone-the production of a sharp working edge-and model this behaviour over evolutionary time to reassess the evolutionary efficiency of stone tool technology. Using more than 19,000 flakes from 81 assemblages spanning two million years, we show that greater production of sharp edges was followed by increased variability in this behaviour. We propose that a diachronic increase in this variability was related to a higher intensity of interrelations between different behaviours involving the use and management of stone resources that gave fitness advantages in particular environmental contexts. The long-term trends identified in this study inform us that the evolutionary efficiency of stone tool technology was not inherently in advanced tool forms and production techniques, but emerged within the contingencies of hominin interaction with local environments.}, } @article {pmid29507349, year = {2018}, author = {He, F and Bhoobalan-Chitty, Y and Van, LB and Kjeldsen, AL and Dedola, M and Makarova, KS and Koonin, EV and Brodersen, DE and Peng, X}, title = {Anti-CRISPR proteins encoded by archaeal lytic viruses inhibit subtype I-D immunity.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {461-469}, doi = {10.1038/s41564-018-0120-z}, pmid = {29507349}, issn = {2058-5276}, abstract = {Viruses employ a range of strategies to counteract the prokaryotic adaptive immune system, clustered regularly interspaced short palindromic repeats and CRISPR-associated proteins (CRISPR-Cas), including mutational escape and physical blocking of enzymatic function using anti-CRISPR proteins (Acrs). Acrs have been found in many bacteriophages but so far not in archaeal viruses, despite the near ubiquity of CRISPR-Cas systems in archaea. Here, we report the functional and structural characterization of two archaeal Acrs from the lytic rudiviruses, SIRV2 and SIRV3. We show that a 4 kb deletion in the SIRV2 genome dramatically reduces infectivity in Sulfolobus islandicus LAL14/1 that carries functional CRISPR-Cas subtypes I-A, I-D and III-B. Subsequent insertion of a single gene from SIRV3, gp02 (AcrID1), which is conserved in the deleted fragment, successfully restored infectivity. We demonstrate that AcrID1 protein inhibits the CRISPR-Cas subtype I-D system by interacting directly with Cas10d protein, which is required for the interference stage. Sequence and structural analysis of AcrID1 show that it belongs to a conserved family of compact, dimeric αβ-sandwich proteins characterized by extreme pH and temperature stability and a tendency to form protein fibres. We identify about 50 homologues of AcrID1 in four archaeal viral families demonstrating the broad distribution of this group of anti-CRISPR proteins.}, } @article {pmid29507254, year = {2018}, author = {Park, H and Ovchinnikov, S and Kim, DE and DiMaio, F and Baker, D}, title = {Protein homology model refinement by large-scale energy optimization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3054-3059}, pmid = {29507254}, issn = {1091-6490}, support = {R01 GM092802/GM/NIGMS NIH HHS/United States ; R01 GM123089/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Computational Biology/methods ; *Computer Simulation ; *Models, Chemical ; Models, Molecular ; Molecular Dynamics Simulation ; Protein Conformation ; Protein Folding ; Thermodynamics ; }, abstract = {Proteins fold to their lowest free-energy structures, and hence the most straightforward way to increase the accuracy of a partially incorrect protein structure model is to search for the lowest-energy nearby structure. This direct approach has met with little success for two reasons: first, energy function inaccuracies can lead to false energy minima, resulting in model degradation rather than improvement; and second, even with an accurate energy function, the search problem is formidable because the energy only drops considerably in the immediate vicinity of the global minimum, and there are a very large number of degrees of freedom. Here we describe a large-scale energy optimization-based refinement method that incorporates advances in both search and energy function accuracy that can substantially improve the accuracy of low-resolution homology models. The method refined low-resolution homology models into correct folds for 50 of 84 diverse protein families and generated improved models in recent blind structure prediction experiments. Analyses of the basis for these improvements reveal contributions from both the improvements in conformational sampling techniques and the energy function.}, } @article {pmid29507253, year = {2018}, author = {}, title = {Correction for Muretta et al., A posttranslational modification of the mitotic kinesin Eg5 that enhances its mechanochemical coupling and alters its mitotic function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2665}, doi = {10.1073/pnas.1802910115}, pmid = {29507253}, issn = {1091-6490}, } @article {pmid29507252, year = {2018}, author = {Lopez-Redondo, ML and Coudray, N and Zhang, Z and Alexopoulos, J and Stokes, DL}, title = {Structural basis for the alternating access mechanism of the cation diffusion facilitator YiiP.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3042-3047}, pmid = {29507252}, issn = {1091-6490}, support = {P41 GM103310/GM/NIGMS NIH HHS/United States ; R01 GM095747/GM/NIGMS NIH HHS/United States ; U54 GM094598/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Escherichia coli/genetics/metabolism ; Escherichia coli Proteins/*chemistry/*physiology ; Membrane Transport Proteins/*chemistry/*physiology ; Models, Molecular ; Protein Conformation ; Protein Domains ; }, abstract = {YiiP is a dimeric antiporter from the cation diffusion facilitator family that uses the proton motive force to transport Zn2+ across bacterial membranes. Previous work defined the atomic structure of an outward-facing conformation, the location of several Zn2+ binding sites, and hydrophobic residues that appear to control access to the transport sites from the cytoplasm. A low-resolution cryo-EM structure revealed changes within the membrane domain that were associated with the alternating access mechanism for transport. In the current work, the resolution of this cryo-EM structure has been extended to 4.1 Å. Comparison with the X-ray structure defines the differences between inward-facing and outward-facing conformations at an atomic level. These differences include rocking and twisting of a four-helix bundle that harbors the Zn2+ transport site and controls its accessibility within each monomer. As previously noted, membrane domains are closely associated in the dimeric structure from cryo-EM but dramatically splayed apart in the X-ray structure. Cysteine crosslinking was used to constrain these membrane domains and to show that this large-scale splaying was not necessary for transport activity. Furthermore, dimer stability was not compromised by mutagenesis of elements in the cytoplasmic domain, suggesting that the extensive interface between membrane domains is a strong determinant of dimerization. As with other secondary transporters, this interface could provide a stable scaffold for movements of the four-helix bundle that confers alternating access of these ions to opposite sides of the membrane.}, } @article {pmid29507251, year = {2018}, author = {Abu, F and Wang, JG and Oh, Y and Deng, J and Neubert, TA and Suh, GSB}, title = {Communicating the nutritional value of sugar in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2829-E2838}, pmid = {29507251}, issn = {1091-6490}, support = {R01 DC012791/DC/NIDCD NIH HHS/United States ; R01 DK106636/DK/NIDDK NIH HHS/United States ; R01 DK116294/DK/NIDDK NIH HHS/United States ; }, mesh = {Animal Communication ; Animals ; Drosophila/genetics/*physiology ; Drosophila Proteins/genetics/metabolism ; Female ; Male ; Mutation ; Nerve Tissue Proteins/genetics/metabolism ; Nutritive Value ; Olfactory Bulb/physiology ; Paired Box Transcription Factors/genetics/metabolism ; Pheromones/*metabolism ; Receptors, Cell Surface/genetics/metabolism ; Species Specificity ; *Sugars/metabolism/pharmacology ; }, abstract = {Sweet-insensitive Drosophila mutants are unable to readily identify sugar. In presence of wild-type (WT) flies, however, these mutant flies demonstrated a marked increase in their preference for nutritive sugar. Real-time recordings of starved WT flies revealed that these flies discharge a drop from their gut end after consuming nutritive sugars, but not nonnutritive sugars. We proposed that the drop may contain a molecule(s) named calorie-induced secreted factor (CIF), which serves as a signal to inform other flies about its nutritional value. Consistent with this, we observed a robust preference of flies for nutritive sugar containing CIF over nutritive sugar without CIF. Feeding appears to be a prerequisite for the release of CIF, given that fed flies did not produce it. Additionally, correlation analyses and pharmacological approaches suggest that the nutritional value, rather than the taste, of the consumed sugar correlates strongly with the amount (or intensity) of the released CIF. We observed that the release of this attractant signal requires the consumption of macronutrients, specifically nutritive sugars and l-enantiomer essential amino acids (l-eAAs), but it is negligibly released when flies are fed nonnutritive sugars, unnatural d-enantiomer essential amino acids (d-eAAs), fatty acids, alcohol, or salts. Finally, CIF (i) is not detected by the olfactory system, (ii) is not influenced by the sex of the fly, and (iii) is not limited to one species of Drosophila.}, } @article {pmid29507250, year = {2018}, author = {Hudson, BH and Hale, AT and Irving, RP and Li, S and York, JD}, title = {Modulation of intestinal sulfur assimilation metabolism regulates iron homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3000-3005}, pmid = {29507250}, issn = {1091-6490}, support = {F30 HL143826/HL/NHLBI NIH HHS/United States ; T32 GM007347/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Gene Expression Regulation, Enzymologic ; Genotype ; Homeostasis/*physiology ; Intestines/*physiology ; Iron/*metabolism ; Mice ; Mice, Knockout ; Nucleotidases ; Sulfur/*metabolism ; }, abstract = {Sulfur assimilation is an evolutionarily conserved pathway that plays an essential role in cellular and metabolic processes, including sulfation, amino acid biosynthesis, and organismal development. We report that loss of a key enzymatic component of the pathway, bisphosphate 3'-nucleotidase (Bpnt1), in mice, both whole animal and intestine-specific, leads to iron-deficiency anemia. Analysis of mutant enterocytes demonstrates that modulation of their substrate 3'-phosphoadenosine 5'-phosphate (PAP) influences levels of key iron homeostasis factors involved in dietary iron reduction, import and transport, that in part mimic those reported for the loss of hypoxic-induced transcription factor, HIF-2α. Our studies define a genetic basis for iron-deficiency anemia, a molecular approach for rescuing loss of nucleotidase function, and an unanticipated link between nucleotide hydrolysis in the sulfur assimilation pathway and iron homeostasis.}, } @article {pmid29507249, year = {2018}, author = {Sequeira, S and Kavanaugh, D and MacKenzie, DA and Šuligoj, T and Walpole, S and Leclaire, C and Gunning, AP and Latousakis, D and Willats, WGT and Angulo, J and Dong, C and Juge, N}, title = {Structural basis for the role of serine-rich repeat proteins from Lactobacillus reuteri in gut microbe-host interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2706-E2715}, pmid = {29507249}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; BB/J004529/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/K019554/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P010660/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; WT106121MA//Wellcome Trust/United Kingdom ; }, mesh = {Adhesins, Bacterial/chemistry/metabolism ; Animals ; Bacterial Adhesion/physiology ; Bacterial Proteins/*chemistry/genetics/metabolism ; Binding Sites ; Crystallography, X-Ray ; Epithelial Cells/microbiology ; *Gastrointestinal Microbiome ; Hydrogen-Ion Concentration ; Lactobacillus reuteri/chemistry/*physiology ; Mice ; *Microbial Interactions ; Molecular Dynamics Simulation ; Pectins/metabolism ; Protein Folding ; Repetitive Sequences, Amino Acid ; Sequence Homology, Amino Acid ; Serine ; }, abstract = {Lactobacillus reuteri, a Gram-positive bacterial species inhabiting the gastrointestinal tract of vertebrates, displays remarkable host adaptation. Previous mutational analyses of rodent strain L. reuteri 100-23C identified a gene encoding a predicted surface-exposed serine-rich repeat protein (SRRP100-23) that was vital for L. reuteri biofilm formation in mice. SRRPs have emerged as an important group of surface proteins on many pathogens, but no structural information is available in commensal bacteria. Here we report the 2.00-Å and 1.92-Å crystal structures of the binding regions (BRs) of SRRP100-23 and SRRP53608 from L. reuteri ATCC 53608, revealing a unique β-solenoid fold in this important adhesin family. SRRP53608-BR bound to host epithelial cells and DNA at neutral pH and recognized polygalacturonic acid (PGA), rhamnogalacturonan I, or chondroitin sulfate A at acidic pH. Mutagenesis confirmed the role of the BR putative binding site in the interaction of SRRP53608-BR with PGA. Long molecular dynamics simulations showed that SRRP53608-BR undergoes a pH-dependent conformational change. Together, these findings provide mechanistic insights into the role of SRRPs in host-microbe interactions and open avenues of research into the use of biofilm-forming probiotics against clinically important pathogens.}, } @article {pmid29507248, year = {2018}, author = {Pier, EL and Brauer, M and Filut, A and Kaatz, A and Raclaw, J and Nathan, MJ and Ford, CE and Carnes, M}, title = {Low agreement among reviewers evaluating the same NIH grant applications.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2952-2957}, pmid = {29507248}, issn = {1091-6490}, support = {R01 GM111002/GM/NIGMS NIH HHS/United States ; }, mesh = {Biomedical Research/*economics ; Humans ; *National Institutes of Health (U.S.) ; Observer Variation ; Peer Review, Research/*methods ; United States ; Writing ; }, abstract = {Obtaining grant funding from the National Institutes of Health (NIH) is increasingly competitive, as funding success rates have declined over the past decade. To allocate relatively scarce funds, scientific peer reviewers must differentiate the very best applications from comparatively weaker ones. Despite the importance of this determination, little research has explored how reviewers assign ratings to the applications they review and whether there is consistency in the reviewers' evaluation of the same application. Replicating all aspects of the NIH peer-review process, we examined 43 individual reviewers' ratings and written critiques of the same group of 25 NIH grant applications. Results showed no agreement among reviewers regarding the quality of the applications in either their qualitative or quantitative evaluations. Although all reviewers received the same instructions on how to rate applications and format their written critiques, we also found no agreement in how reviewers "translated" a given number of strengths and weaknesses into a numeric rating. It appeared that the outcome of the grant review depended more on the reviewer to whom the grant was assigned than the research proposed in the grant. This research replicates the NIH peer-review process to examine in detail the qualitative and quantitative judgments of different reviewers examining the same application, and our results have broad relevance for scientific grant peer review.}, } @article {pmid29507247, year = {2018}, author = {Kalas, V and Hibbing, ME and Maddirala, AR and Chugani, R and Pinkner, JS and Mydock-McGrane, LK and Conover, MS and Janetka, JW and Hultgren, SJ}, title = {Structure-based discovery of glycomimetic FmlH ligands as inhibitors of bacterial adhesion during urinary tract infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2819-E2828}, pmid = {29507247}, issn = {1091-6490}, support = {P30 CA091842/CA/NCI NIH HHS/United States ; R01 DK108840/DK/NIDDK NIH HHS/United States ; T32 GM007200/GM/NIGMS NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Adhesins, Escherichia coli/*chemistry/metabolism ; Animals ; Anti-Bacterial Agents/*chemistry/*pharmacology ; Bacterial Adhesion/*drug effects ; Crystallography, X-Ray ; Drug Evaluation, Preclinical/methods ; Escherichia coli Infections/drug therapy/microbiology ; Female ; Galactosides/chemical synthesis/chemistry ; Humans ; Kidney/drug effects/metabolism/microbiology ; Ligands ; Mice, Inbred C3H ; Molecular Docking Simulation ; Molecular Mimicry ; Urinary Tract Infections/drug therapy/*microbiology ; Uropathogenic Escherichia coli/drug effects/pathogenicity ; }, abstract = {Treatment of bacterial infections is becoming a serious clinical challenge due to the global dissemination of multidrug antibiotic resistance, necessitating the search for alternative treatments to disarm the virulence mechanisms underlying these infections. Uropathogenic Escherichia coli (UPEC) employs multiple chaperone-usher pathway pili tipped with adhesins with diverse receptor specificities to colonize various host tissues and habitats. For example, UPEC F9 pili specifically bind galactose or N-acetylgalactosamine epitopes on the kidney and inflamed bladder. Using X-ray structure-guided methods, virtual screening, and multiplex ELISA arrays, we rationally designed aryl galactosides and N-acetylgalactosaminosides that inhibit the F9 pilus adhesin FmlH. The lead compound, 29β-NAc, is a biphenyl N-acetyl-β-galactosaminoside with a Ki of ∼90 nM, representing a major advancement in potency relative to the characteristically weak nature of most carbohydrate-lectin interactions. 29β-NAc binds tightly to FmlH by engaging the residues Y46 through edge-to-face π-stacking with its A-phenyl ring, R142 in a salt-bridge interaction with its carboxylate group, and K132 through water-mediated hydrogen bonding with its N-acetyl group. Administration of 29β-NAc in a mouse urinary tract infection (UTI) model significantly reduced bladder and kidney bacterial burdens, and coadministration of 29β-NAc and mannoside 4Z269, which targets the type 1 pilus adhesin FimH, resulted in greater elimination of bacteria from the urinary tract than either compound alone. Moreover, FmlH specifically binds healthy human kidney tissue in a 29β-NAc-inhibitable manner, suggesting a key role for F9 pili in human kidney colonization. Thus, these glycoside antagonists of FmlH represent a rational antivirulence strategy for UPEC-mediated UTI treatment.}, } @article {pmid29507246, year = {2018}, author = {Pons-Salort, M and Oberste, MS and Pallansch, MA and Abedi, GR and Takahashi, S and Grenfell, BT and Grassly, NC}, title = {The seasonality of nonpolio enteroviruses in the United States: Patterns and drivers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3078-3083}, pmid = {29507246}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; P2C HD047879/HD/NICHD NIH HHS/United States ; 106073/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Climate ; Enterovirus/*classification/*physiology ; Enterovirus Infections/*epidemiology/history/*virology ; History, 20th Century ; History, 21st Century ; Humans ; Population Surveillance ; *Seasons ; United States/epidemiology ; }, abstract = {Nonpolio enteroviruses are diverse and common viruses that can circulate year-round but tend to peak in summer. Although most infections are asymptomatic, they can result in a wide range of neurological and other diseases. Many serotypes circulate every year, and different serotypes predominate in different years, but the drivers of their geographical and temporal dynamics are not understood. We use national enterovirus surveillance data collected by the US Centers for Disease Control and Prevention during 1983-2013, as well as demographic and climatic data for the same period, to study the patterns and drivers of the seasonality of these infections. We find that the seasonal pattern of enterovirus cases is spatially structured in the United States and similar to that observed for historical prevaccination poliomyelitis (1931-1954). We identify latitudinal gradients for the amplitude and the timing of the peak of cases, meaning that those are more regularly distributed all year-round in the south and have a more pronounced peak that arrives later toward the north. The peak is estimated to occur between July and September across the United States, and 1 month earlier than that for historical poliomyelitis. Using mixed-effects models, we find that climate, but not demography, is likely to drive the seasonal pattern of enterovirus cases and that the dew point temperature alone explains ∼30% of the variation in the intensity of transmission. Our study contributes to a better understanding of the epidemiology of enteroviruses, demonstrates important similarities in their circulation dynamics with polioviruses, and identifies potential drivers of their seasonality.}, } @article {pmid29507245, year = {2018}, author = {Beron-Vera, FJ and Hadjighasem, A and Xia, Q and Olascoaga, MJ and Haller, G}, title = {Coherent Lagrangian swirls among submesoscale motions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {}, number = {}, pages = {}, doi = {10.1073/pnas.1701392115}, pmid = {29507245}, issn = {1091-6490}, abstract = {The emergence of coherent Lagrangian swirls (CLSs) among submesoscale motions in the ocean is illustrated. This is done by applying recent nonlinear dynamics tools for Lagrangian coherence detection on a surface flow realization produced by a data-assimilative submesoscale-permitting ocean general circulation model simulation of the Gulf of Mexico. Both mesoscale and submesoscale CLSs are extracted. These extractions prove the relevance of coherent Lagrangian eddies detected in satellite-altimetry-based geostrophic flow data for the arguably more realistic ageostrophic multiscale flow.}, } @article {pmid29507244, year = {2018}, author = {Blanchet, S and Cornu, D and Hatin, I and Grosjean, H and Bertin, P and Namy, O}, title = {Deciphering the reading of the genetic code by near-cognate tRNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3018-3023}, pmid = {29507244}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Base Pairing ; Base Sequence ; Codon ; DNA/*genetics ; Gene Expression Regulation, Fungal ; Genetic Code ; RNA, Transfer/genetics/*metabolism ; Saccharomyces cerevisiae/*metabolism ; }, abstract = {Some codons of the genetic code can be read not only by cognate, but also by near-cognate tRNAs. This flexibility is thought to be conferred mainly by a mismatch between the third base of the codon and the first of the anticodon (the so-called "wobble" position). However, this simplistic explanation underestimates the importance of nucleotide modifications in the decoding process. Using a system in which only near-cognate tRNAs can decode a specific codon, we investigated the role of six modifications of the anticodon, or adjacent nucleotides, of the tRNAs specific for Tyr, Gln, Lys, Trp, Cys, and Arg in Saccharomyces cerevisiae. Modifications almost systematically rendered these tRNAs able to act as near-cognate tRNAs at stop codons, even though they involve noncanonical base pairs, without markedly affecting their ability to decode cognate or near-cognate sense codons. These findings reveal an important effect of modifications to tRNA decoding with implications for understanding the flexibility of the genetic code.}, } @article {pmid29507243, year = {2018}, author = {Zhao, Y and Yang, KR and Wang, Z and Yan, X and Cao, S and Ye, Y and Dong, Q and Zhang, X and Thorne, JE and Jin, L and Materna, KL and Trimpalis, A and Bai, H and Fakra, SC and Zhong, X and Wang, P and Pan, X and Guo, J and Flytzani-Stephanopoulos, M and Brudvig, GW and Batista, VS and Wang, D}, title = {Stable iridium dinuclear heterogeneous catalysts supported on metal-oxide substrate for solar water oxidation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2902-2907}, pmid = {29507243}, issn = {1091-6490}, abstract = {Atomically dispersed catalysts refer to substrate-supported heterogeneous catalysts featuring one or a few active metal atoms that are separated from one another. They represent an important class of materials ranging from single-atom catalysts (SACs) and nanoparticles (NPs). While SACs and NPs have been extensively reported, catalysts featuring a few atoms with well-defined structures are poorly studied. The difficulty in synthesizing such structures has been a critical challenge. Here we report a facile photochemical method that produces catalytic centers consisting of two Ir metal cations, bridged by O and stably bound to a support. Direct evidence unambiguously supporting the dinuclear nature of the catalysts anchored on α-Fe2O3 is obtained by aberration-corrected scanning transmission electron microscopy (AC-STEM). Experimental and computational results further reveal that the threefold hollow binding sites on the OH-terminated surface of α-Fe2O3 anchor the catalysts to provide outstanding stability against detachment or aggregation. The resulting catalysts exhibit high activities toward H2O photooxidation.}, } @article {pmid29507242, year = {2018}, author = {Briese, M and Saal-Bauernschubert, L and Ji, C and Moradi, M and Ghanawi, H and Uhl, M and Appenzeller, S and Backofen, R and Sendtner, M}, title = {hnRNP R and its main interactor, the noncoding RNA 7SK, coregulate the axonal transcriptome of motoneurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2859-E2868}, pmid = {29507242}, issn = {1091-6490}, mesh = {3' Untranslated Regions ; Animals ; Axons/*physiology ; Cell Nucleus/genetics ; Cytosol/metabolism ; Gene Expression Regulation ; Gene Knockdown Techniques ; Heterogeneous-Nuclear Ribonucleoproteins/genetics/*metabolism ; Immunoprecipitation/methods ; Mice ; Motor Neurons/*physiology ; RNA, Messenger/metabolism ; RNA, Small Nuclear/genetics/*metabolism ; Transcriptome/genetics ; }, abstract = {Disturbed RNA processing and subcellular transport contribute to the pathomechanisms of motoneuron diseases such as amyotrophic lateral sclerosis and spinal muscular atrophy. RNA-binding proteins are involved in these processes, but the mechanisms by which they regulate the subcellular diversity of transcriptomes, particularly in axons, are not understood. Heterogeneous nuclear ribonucleoprotein R (hnRNP R) interacts with several proteins involved in motoneuron diseases. It is located in axons of developing motoneurons, and its depletion causes defects in axon growth. Here, we used individual nucleotide-resolution cross-linking and immunoprecipitation (iCLIP) to determine the RNA interactome of hnRNP R in motoneurons. We identified ∼3,500 RNA targets, predominantly with functions in synaptic transmission and axon guidance. Among the RNA targets identified by iCLIP, the noncoding RNA 7SK was the top interactor of hnRNP R. We detected 7SK in the nucleus and also in the cytosol of motoneurons. In axons, 7SK localized in close proximity to hnRNP R, and depletion of hnRNP R reduced axonal 7SK. Furthermore, suppression of 7SK led to defective axon growth that was accompanied by axonal transcriptome alterations similar to those caused by hnRNP R depletion. Using a series of 7SK-deletion mutants, we show that the function of 7SK in axon elongation depends on its interaction with hnRNP R but not with the PTEF-B complex involved in transcriptional regulation. These results propose a role for 7SK as an essential interactor of hnRNP R to regulate its function in axon maintenance.}, } @article {pmid29507241, year = {2018}, author = {Wyatt, LC and Moshnikova, A and Crawford, T and Engelman, DM and Andreev, OA and Reshetnyak, YK}, title = {Peptides of pHLIP family for targeted intracellular and extracellular delivery of cargo molecules to tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2811-E2818}, pmid = {29507241}, issn = {1091-6490}, support = {P20 GM103430/GM/NIGMS NIH HHS/United States ; R01 GM073857/GM/NIGMS NIH HHS/United States ; }, mesh = {Amanitins/chemistry ; Animals ; Antineoplastic Agents/*administration & dosage/chemistry ; Circular Dichroism ; Drug Delivery Systems/*methods ; Female ; HeLa Cells ; Humans ; Hydrogen-Ion Concentration ; Lipid Bilayers/chemistry ; Liposomes/chemistry ; Membrane Proteins/*chemistry/genetics ; Mice, Inbred BALB C ; Neoplasms, Experimental/drug therapy ; Peptides/*administration & dosage/chemistry/pharmacokinetics ; Polyethylene Glycols/chemistry ; Tissue Distribution ; }, abstract = {The pH (low) insertion peptides (pHLIPs) target acidity at the surfaces of cancer cells and show utility in a wide range of applications, including tumor imaging and intracellular delivery of therapeutic agents. Here we report pHLIP constructs that significantly improve the targeted delivery of agents into tumor cells. The investigated constructs include pHLIP bundles (conjugates consisting of two or four pHLIP peptides linked by polyethylene glycol) and Var3 pHLIPs containing either the nonstandard amino acid, γ-carboxyglutamic acid, or a glycine-leucine-leucine motif. The performance of the constructs in vitro and in vivo was compared with previous pHLIP variants. A wide range of experiments was performed on nine constructs including (i) biophysical measurements using steady-state and kinetic fluorescence, circular dichroism, and oriented circular dichroism to study the pH-dependent insertion of pHLIP variants across the membrane lipid bilayer; (ii) cell viability assays to gauge the pH-dependent potency of peptide-toxin constructs by assessing the intracellular delivery of the polar, cell-impermeable cargo molecule amanitin at physiological and low pH (pH 7.4 and 6.0, respectively); and (iii) tumor targeting and biodistribution measurements using fluorophore-peptide conjugates in a breast cancer mouse model. The main principles of the design of pHLIP variants for a range of medical applications are discussed.}, } @article {pmid29507240, year = {2018}, author = {Schrader, AM and Monroe, JI and Sheil, R and Dobbs, HA and Keller, TJ and Li, Y and Jain, S and Shell, MS and Israelachvili, JN and Han, S}, title = {Surface chemical heterogeneity modulates silica surface hydration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2890-2895}, pmid = {29507240}, issn = {1091-6490}, abstract = {An in-depth knowledge of the interaction of water with amorphous silica is critical to fundamental studies of interfacial hydration water, as well as to industrial processes such as catalysis, nanofabrication, and chromatography. Silica has a tunable surface comprising hydrophilic silanol groups and moderately hydrophobic siloxane groups that can be interchanged through thermal and chemical treatments. Despite extensive studies of silica surfaces, the influence of surface hydrophilicity and chemical topology on the molecular properties of interfacial water is not well understood. In this work, we controllably altered the surface silanol density, and measured surface water diffusivity using Overhauser dynamic nuclear polarization (ODNP) and complementary silica-silica interaction forces across water using a surface forces apparatus (SFA). The results show that increased silanol density generally leads to slower water diffusivity and stronger silica-silica repulsion at short aqueous separations (less than ∼4 nm). Both techniques show sharp changes in hydration properties at intermediate silanol densities (2.0-2.9 nm-2). Molecular dynamics simulations of model silica-water interfaces corroborate the increase in water diffusivity with silanol density, and furthermore show that even on a smooth and crystalline surface at a fixed silanol density, adjusting the spatial distribution of silanols results in a range of surface water diffusivities spanning ∼10%. We speculate that a critical silanol cluster size or connectivity parameter could explain the sharp transition in our results, and can modulate wettability, colloidal interactions, and surface reactions, and thus is a phenomenon worth further investigation on silica and chemically heterogeneous surfaces.}, } @article {pmid29507239, year = {2018}, author = {Bascom, CS and Winship, LJ and Bezanilla, M}, title = {Simultaneous imaging and functional studies reveal a tight correlation between calcium and actin networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2869-E2878}, pmid = {29507239}, issn = {1091-6490}, mesh = {Actin Cytoskeleton/metabolism ; Actins/analysis/*metabolism ; Bryopsida/cytology/genetics/*growth & development/*metabolism ; Calcium/analysis/*metabolism ; Cytosol/metabolism ; Fluorescent Dyes/metabolism ; Lab-On-A-Chip Devices ; Molecular Imaging/instrumentation/methods ; Plant Cells/metabolism ; Plants, Genetically Modified ; Wavelet Analysis ; }, abstract = {Tip-growing cells elongate in a highly polarized manner via focused secretion of flexible cell-wall material. Calcium has been implicated as a vital factor in regulating the deposition of cell-wall material. However, deciphering the molecular and mechanistic calcium targets in vivo has remained challenging. Here, we investigated intracellular calcium dynamics in the moss Physcomitrella patens, which provides a system with an abundant source of genetically identical tip-growing cells, excellent cytology, and a large molecular genetic tool kit. To visualize calcium we used a genetically encoded cytosolic FRET probe, revealing a fluctuating tipward gradient with a complex oscillatory profile. Wavelet analysis coupled with a signal-sifting algorithm enabled the quantitative comparison of the calcium behavior in cells where growth was inhibited mechanically, pharmacologically, or genetically. We found that cells with suppressed growth have calcium oscillatory profiles with longer frequencies, suggesting that there is a feedback between the calcium gradient and growth. To investigate the mechanistic basis for this feedback we simultaneously imaged cytosolic calcium and actin, which has been shown to be essential for tip growth. We found that high cytosolic calcium promotes disassembly of a tip-focused actin spot, while low calcium promotes assembly. In support of this, abolishing the calcium gradient resulted in dramatic actin accumulation at the tip. Together these data demonstrate that tipward calcium is quantitatively linked to actin accumulation in vivo and that the moss P. patens provides a powerful system to uncover mechanistic links between calcium, actin, and growth.}, } @article {pmid29507238, year = {2018}, author = {Gong, Z and Szczesny, SE and Caliari, SR and Charrier, EE and Chaudhuri, O and Cao, X and Lin, Y and Mauck, RL and Janmey, PA and Burdick, JA and Shenoy, VB}, title = {Matching material and cellular timescales maximizes cell spreading on viscoelastic substrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2686-E2695}, pmid = {29507238}, issn = {1091-6490}, support = {R01 EB017753/EB/NIBIB NIH HHS/United States ; }, mesh = {3T3 Cells ; Animals ; Cell Adhesion/*physiology ; Cell Culture Techniques/*instrumentation/methods ; Extracellular Matrix/*chemistry/metabolism ; Focal Adhesions/metabolism ; Humans ; Hydrogels ; Integrins/metabolism ; Mesenchymal Stem Cells/cytology/physiology ; Mice ; *Models, Biological ; Monte Carlo Method ; Rheology/methods ; Surface Properties ; Viscosity ; }, abstract = {Recent evidence has shown that, in addition to rigidity, the viscous response of the extracellular matrix (ECM) significantly affects the behavior and function of cells. However, the mechanism behind such mechanosensitivity toward viscoelasticity remains unclear. In this study, we systematically examined the dynamics of motor clutches (i.e., focal adhesions) formed between the cell and a viscoelastic substrate using analytical methods and direct Monte Carlo simulation. Interestingly, we observe that, for low ECM rigidity, maximum cell spreading is achieved at an optimal level of viscosity in which the substrate relaxation time falls between the timescale for clutch binding and its characteristic binding lifetime. That is, viscosity serves to stiffen soft substrates on a timescale faster than the clutch off-rate, which enhances cell-ECM adhesion and cell spreading. On the other hand, for substrates that are stiff, our model predicts that viscosity will not influence cell spreading, since the bound clutches are saturated by the elevated stiffness. The model was tested and validated using experimental measurements on three different material systems and explained the different observed effects of viscosity on each substrate. By capturing the mechanism by which substrate viscoelasticity affects cell spreading across a wide range of material parameters, our analytical model provides a useful tool for designing biomaterials that optimize cellular adhesion and mechanosensing.}, } @article {pmid29507237, year = {2018}, author = {Zhang, X and Barraza, KM and Beauchamp, JL}, title = {Cholesterol provides nonsacrificial protection of membrane lipids from chemical damage at air-water interface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3255-3260}, pmid = {29507237}, issn = {1091-6490}, mesh = {Cholesterol/*chemistry ; Lipid Bilayers/*chemistry ; Membrane Lipids/*chemistry ; Oxidation-Reduction ; Phosphatidylcholines/*chemistry ; Surface Properties ; Water/*chemistry ; }, abstract = {The role of cholesterol in bilayer and monolayer lipid membranes has been of great interest. On the biophysical front, cholesterol significantly increases the order of the lipid packing, lowers the membrane permeability, and maintains membrane fluidity by forming liquid-ordered-phase lipid rafts. However, direct observation of any influence on membrane chemistry related to these cholesterol-induced physical properties has been absent. Here we report that the addition of 30 mol % cholesterol to 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) or 1-palmitoyl-2-oleoyl-sn-glycero-3-phospho-(1'-rac-glycerol) (POPG) monolayers at the air-water interface greatly reduces the oxidation and ester linkage cleavage chemistries initiated by potent chemicals such as OH radicals and HCl vapor, respectively. These results shed light on the indispensable chemoprotective function of cholesterol in lipid membranes. Another significant finding is that OH oxidation of unsaturated lipids generates Criegee intermediate, which is an important radical involved in many atmospheric processes.}, } @article {pmid29507236, year = {2018}, author = {Doong, SJ and Gupta, A and Prather, KLJ}, title = {Layered dynamic regulation for improving metabolic pathway productivity in Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2964-2969}, pmid = {29507236}, issn = {1091-6490}, support = {T32 GM008334/GM/NIGMS NIH HHS/United States ; }, mesh = {Biosensing Techniques ; Escherichia coli K12/enzymology/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Gene Expression Regulation, Bacterial/physiology ; Gene Expression Regulation, Enzymologic/physiology ; Glucaric Acid/*metabolism ; Inositol/metabolism ; Metabolic Engineering/*methods ; Metabolic Networks and Pathways/genetics/*physiology ; }, abstract = {Microbial production of value-added chemicals from biomass is a sustainable alternative to chemical synthesis. To improve product titer, yield, and selectivity, the pathways engineered into microbes must be optimized. One strategy for optimization is dynamic pathway regulation, which modulates expression of pathway-relevant enzymes over the course of fermentation. Metabolic engineers have used dynamic regulation to redirect endogenous flux toward product formation, balance the production and consumption rates of key intermediates, and suppress production of toxic intermediates until later in the fermentation. Most cases, however, have utilized a single strategy for dynamically regulating pathway fluxes. Here we layer two orthogonal, autonomous, and tunable dynamic regulation strategies to independently modulate expression of two different enzymes to improve production of D-glucaric acid from a heterologous pathway. The first strategy uses a previously described pathway-independent quorum sensing system to dynamically knock down glycolytic flux and redirect carbon into production of glucaric acid, thereby switching cells from "growth" to "production" mode. The second strategy, developed in this work, uses a biosensor for myo-inositol (MI), an intermediate in the glucaric acid production pathway, to induce expression of a downstream enzyme upon sufficient buildup of MI. The latter, pathway-dependent strategy leads to a 2.5-fold increase in titer when used in isolation and a fourfold increase when added to a strain employing the former, pathway-independent regulatory system. The dual-regulation strain produces nearly 2 g/L glucaric acid, representing the highest glucaric acid titer reported to date in Escherichia coli K-12 strains.}, } @article {pmid29507235, year = {2018}, author = {Watanabe, R and Sakuragi, T and Noji, H and Nagata, S}, title = {Single-molecule analysis of phospholipid scrambling by TMEM16F.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3066-3071}, pmid = {29507235}, issn = {1091-6490}, mesh = {Animals ; Anoctamins/genetics/*metabolism ; Cell Line ; Kinetics ; Membranes, Artificial ; Mice ; Phospholipid Transfer Proteins/genetics/*metabolism ; Phospholipids/*chemistry/*metabolism ; Protein Array Analysis ; }, abstract = {Transmembrane protein 16F (TMEM16F) is a Ca2+-dependent phospholipid scramblase that translocates phospholipids bidirectionally between the leaflets of the plasma membrane. Phospholipid scrambling of TMEM16F causes exposure of phosphatidylserine in activated platelets to induce blood clotting and in differentiated osteoblasts to promote bone mineralization. Despite the importance of TMEM16F-mediated phospholipid scrambling in various biological reactions, the fundamental features of the scrambling reaction remain elusive due to technical difficulties in the preparation of a platform for assaying scramblase activity in vitro. Here, we established a method to express and purify mouse TMEM16F as a dimeric molecule by constructing a stable cell line and developed a microarray containing membrane bilayers with asymmetrically distributed phospholipids as a platform for single-molecule scramblase assays. The purified TMEM16F was integrated into the microarray, and monitoring of phospholipid translocation showed that a single TMEM16F molecule transported phospholipids nonspecifically between the membrane bilayers in a Ca2+-dependent manner. Thermodynamic analysis of the reaction indicated that TMEM16F transported 4.5 × 104 lipids per second at 25 °C, with an activation free energy of 47 kJ/mol. These biophysical features were similar to those observed with channels, which transport substrates by facilitating diffusion, and supported the stepping-stone model for the TMEM16F phospholipid scramblase.}, } @article {pmid29507234, year = {2018}, author = {Patrick, JW and Boone, CD and Liu, W and Conover, GM and Liu, Y and Cong, X and Laganowsky, A}, title = {Allostery revealed within lipid binding events to membrane proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2976-2981}, pmid = {29507234}, issn = {1091-6490}, support = {DP2 GM123486/GM/NIGMS NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 OD021527/OD/NIH HHS/United States ; }, mesh = {Bacterial Outer Membrane Proteins ; Binding Sites ; Cation Transport Proteins/genetics/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Gene Expression Regulation, Bacterial/*physiology ; Lipid Metabolism/*physiology ; Lipids/chemistry ; Membrane Proteins/metabolism ; Models, Molecular ; Protein Binding ; Protein Conformation ; }, abstract = {Membrane proteins interact with a myriad of lipid species in the biological membrane, leading to a bewildering number of possible protein-lipid assemblies. Despite this inherent complexity, the identification of specific protein-lipid interactions and the crucial role of lipids in the folding, structure, and function of membrane proteins is emerging from an increasing number of reports. Fundamental questions remain, however, regarding the ability of specific lipid binding events to membrane proteins to alter remote binding sites for lipids of a different type, a property referred to as allostery [Monod J, Wyman J, Changeux JP (1965) J Mol Biol 12:88-118]. Here, we use native mass spectrometry to determine the allosteric nature of heterogeneous lipid binding events to membrane proteins. We monitored individual lipid binding events to the ammonia channel (AmtB) from Escherichia coli, enabling determination of their equilibrium binding constants. We found that different lipid pairs display a range of allosteric modulation. In particular, the binding of phosphatidylethanolamine and cardiolipin-like molecules to AmtB exhibited the largest degree of allosteric modulation, inspiring us to determine the cocrystal structure of AmtB in this lipid environment. The 2.45-Å resolution structure reveals a cardiolipin-like molecule bound to each subunit of the trimeric complex. Mutation of a single residue in AmtB abolishes the positive allosteric modulation observed for binding phosphatidylethanolamine and cardiolipin-like molecules. Our results demonstrate that specific lipid-protein interactions can act as allosteric modulators for the binding of different lipid types to integral membrane proteins.}, } @article {pmid29507233, year = {2018}, author = {Rai, R and Krishnan, BP and Sureshan, KM}, title = {Chirality-controlled spontaneous twisting of crystals due to thermal topochemical reaction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2896-2901}, pmid = {29507233}, issn = {1091-6490}, abstract = {Crystals that show mechanical response against various stimuli are of great interest. These stimuli induce polymorphic transitions, isomerizations, or chemical reactions in the crystal and the strain generated between the daughter and parent domains is transcribed into mechanical response. We observed that the crystals of modified dipeptide LL (N3-l-Ala-l-Val-NHCH2C≡CH) undergo spontaneous twisting to form right-handed twisted crystals not only at room temperature but also at 0 °C over time. Using various spectroscopic techniques, we have established that the twisting is due to the spontaneous topochemical azide-alkyne cycloaddition (TAAC) reaction at room temperature or lower temperatures. The rate of twisting can be increased by heating, exploiting the faster kinetics of the TAAC reaction at higher temperatures. To address the role of molecular chirality in the direction of twisting the enantiomer of dipeptide LL, N3-d-Ala-d-Val-NHCH2C≡CH (DD), was synthesized and topochemical reactivity and mechanoresponse of its crystals were studied. We have found that dipeptide DD not only underwent TAAC reaction, giving 1,4-triazole-linked pseudopolypeptides of d-amino acids, but also underwent twisting with opposite handedness (left-handed twisting), establishing the role of molecular chirality in controlling the direction of mechanoresponse. This paper reports (i) a mechanical response due to a thermal reaction and (ii) a spontaneous mechanical response in crystals and (iii) explains the role of molecular chirality in the handedness of the macroscopic mechanical response.}, } @article {pmid29507232, year = {2018}, author = {Oskarsson, ME and Hermansson, E and Wang, Y and Welsh, N and Presto, J and Johansson, J and Westermark, GT}, title = {BRICHOS domain of Bri2 inhibits islet amyloid polypeptide (IAPP) fibril formation and toxicity in human beta cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2752-E2761}, pmid = {29507232}, issn = {1091-6490}, mesh = {Amyloid/*metabolism ; Animals ; Animals, Genetically Modified ; Apoptosis/physiology ; Brain/metabolism/pathology ; Cells, Cultured ; Diabetes Mellitus, Type 2/*metabolism/pathology ; Drosophila melanogaster/genetics ; Female ; Glucose/pharmacology ; Humans ; Insulin-Secreting Cells/*metabolism/pathology ; Islet Amyloid Polypeptide/genetics/*metabolism ; Islets of Langerhans/drug effects/metabolism/pathology ; Membrane Glycoproteins/genetics/immunology/*metabolism ; Palmitic Acid/pharmacology ; Protein Domains ; }, abstract = {Aggregation of islet amyloid polypeptide (IAPP) into amyloid fibrils in islets of Langerhans is associated with type 2 diabetes, and formation of toxic IAPP species is believed to contribute to the loss of insulin-producing beta cells. The BRICHOS domain of integral membrane protein 2B (Bri2), a transmembrane protein expressed in several peripheral tissues and in the brain, has recently been shown to prevent fibril formation and toxicity of Aβ42, an amyloid-forming peptide in Alzheimer disease. In this study, we demonstrate expression of Bri2 in human islets and in the human beta-cell line EndoC-βH1. Bri2 colocalizes with IAPP intracellularly and is present in amyloid deposits in patients with type 2 diabetes. The BRICHOS domain of Bri2 effectively inhibits fibril formation in vitro and instead redirects IAPP into formation of amorphous aggregates. Reduction of endogenous Bri2 in EndoC-βH1 cells with siRNA increases sensitivity to metabolic stress leading to cell death while a concomitant overexpression of Bri2 BRICHOS is protective. Also, coexpression of IAPP and Bri2 BRICHOS in lateral ventral neurons of Drosophila melanogaster results in an increased cell survival. IAPP is considered to be the most amyloidogenic peptide known, and described findings identify Bri2, or in particular its BRICHOS domain, as an important potential endogenous inhibitor of IAPP aggregation and toxicity, with the potential to be a possible target for the treatment of type 2 diabetes.}, } @article {pmid29507231, year = {2018}, author = {Paz, A and Claxton, DP and Kumar, JP and Kazmier, K and Bisignano, P and Sharma, S and Nolte, SA and Liwag, TM and Nayak, V and Wright, EM and Grabe, M and Mchaourab, HS and Abramson, J}, title = {Conformational transitions of the sodium-dependent sugar transporter, vSGLT.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2742-E2751}, pmid = {29507231}, issn = {1091-6490}, support = {R01 DK019567/DK/NIDDK NIH HHS/United States ; R01 GM078844/GM/NIGMS NIH HHS/United States ; R01 GM089740/GM/NIGMS NIH HHS/United States ; U54 GM087519/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/chemistry/metabolism ; Biological Transport, Active ; Cysteine/genetics ; Electron Spin Resonance Spectroscopy/methods ; Galactose/metabolism ; Membrane Lipids/chemistry/metabolism ; Micelles ; Models, Molecular ; Molecular Dynamics Simulation ; Mutation ; Protein Conformation ; Sodium/metabolism ; Sodium-Glucose Transport Proteins/*chemistry/*metabolism ; Vibrio parahaemolyticus/chemistry ; }, abstract = {Sodium-dependent transporters couple the flow of Na+ ions down their electrochemical potential gradient to the uphill transport of various ligands. Many of these transporters share a common core structure composed of a five-helix inverted repeat and deliver their cargo utilizing an alternating-access mechanism. A detailed characterization of inward-facing conformations of the Na+-dependent sugar transporter from Vibrio parahaemolyticus (vSGLT) has previously been reported, but structural details on additional conformations and on how Na+ and ligand influence the equilibrium between other states remains unknown. Here, double electron-electron resonance spectroscopy, structural modeling, and molecular dynamics are utilized to deduce ligand-dependent equilibria shifts of vSGLT in micelles. In the absence and presence of saturating amounts of Na+, vSGLT favors an inward-facing conformation. Upon binding both Na+ and sugar, the equilibrium shifts toward either an outward-facing or occluded conformation. While Na+ alone does not stabilize the outward-facing state, gating charge calculations together with a kinetic model of transport suggest that the resting negative membrane potential of the cell, absent in detergent-solubilized samples, may stabilize vSGLT in an outward-open conformation where it is poised for binding external sugars. In total, these findings provide insights into ligand-induced conformational selection and delineate the transport cycle of vSGLT.}, } @article {pmid29507230, year = {2018}, author = {Wu, Y and Li, X and Jia, J and Zhang, Y and Li, J and Zhu, Z and Wang, H and Tang, J and Hu, J}, title = {Transmembrane E3 ligase RNF183 mediates ER stress-induced apoptosis by degrading Bcl-xL.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2762-E2771}, pmid = {29507230}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Apoptosis/physiology ; COS Cells ; Cercopithecus aethiops ; Endoplasmic Reticulum/metabolism ; Endoplasmic Reticulum Stress/*physiology ; Endoribonucleases/metabolism ; HeLa Cells ; Humans ; MicroRNAs/metabolism ; Protein-Serine-Threonine Kinases/metabolism ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitination ; Unfolded Protein Response/physiology ; bcl-X Protein/genetics/*metabolism ; }, abstract = {The accumulation of misfolded proteins in the endoplasmic reticulum (ER) causes ER stress and triggers the unfolded protein response (UPR). Failure to resolve ER stress leads to apoptotic cell death via a yet unclear mechanism. Here, we show that RNF183, a membrane-spanning RING finger protein, localizes to the ER and exhibits classic E3 ligase activities. Sustained ER stress induced by different treatments increases RNF183 protein levels posttranscriptionally in an IRE1α-dependent manner. Activated IRE1 reduces the level of miR-7, which increases the stability of RNF183 transcripts. In addition, overexpression of RNF183 leads to increased apoptosis and its depletion alleviates ER stress-induced apoptosis. Furthermore, RNF183 interacts with Bcl-xL, an antiapoptotic member of the Bcl-2 family, and polyubiquitinates Bcl-xL for degradation. Thus, RNF183 plays an important role in executing programmed cell death upon prolonged ER stress, likely by inducing apoptosis through Bcl-xL.}, } @article {pmid29507229, year = {2018}, author = {Giurisato, E and Xu, Q and Lonardi, S and Telfer, B and Russo, I and Pearson, A and Finegan, KG and Wang, W and Wang, J and Gray, NS and Vermi, W and Xia, Z and Tournier, C}, title = {Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2801-E2810}, pmid = {29507229}, issn = {1091-6490}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antigens, CD/metabolism ; Antigens, Differentiation, Myelomonocytic/metabolism ; Cell Polarity ; Humans ; Macrophages/*metabolism/pathology ; Mice, Inbred C57BL ; Mice, Transgenic ; Mitogen-Activated Protein Kinase 7/genetics/*metabolism ; Neoplasms/*metabolism/*pathology ; Phosphorylation ; Receptors, Cell Surface/metabolism ; STAT3 Transcription Factor/genetics/*metabolism ; Tyrosine/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Owing to the prevalence of tumor-associated macrophages (TAMs) in cancer and their unique influence upon disease progression and malignancy, macrophage-targeted interventions have attracted notable attention in cancer immunotherapy. However, tractable targets to reduce TAM activities remain very few and far between because the signaling mechanisms underpinning protumor macrophage phenotypes are largely unknown. Here, we have investigated the role of the extracellular-regulated protein kinase 5 (ERK5) as a determinant of macrophage polarity. We report that the growth of carcinoma grafts was halted in myeloid ERK5-deficient mice. Coincidentally, targeting ERK5 in macrophages induced a transcriptional switch in favor of proinflammatory mediators. Further molecular analyses demonstrated that activation of the signal transducer and activator of transcription 3 (STAT3) via Tyr705 phosphorylation was impaired in erk5-deleted TAMs. Our study thus suggests that blocking ERK5 constitutes a treatment strategy to reprogram macrophages toward an antitumor state by inhibiting STAT3-induced gene expression.}, } @article {pmid29507228, year = {2018}, author = {Zhou, S and Pettersson, P and Huang, J and Sjöholm, J and Sjöstrand, D and Pomès, R and Högbom, M and Brzezinski, P and Mäler, L and Ädelroth, P}, title = {Solution NMR structure of yeast Rcf1, a protein involved in respiratory supercomplex formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3048-3053}, pmid = {29507228}, issn = {1091-6490}, mesh = {Binding Sites ; Computer Simulation ; Cytochromes c/chemistry/metabolism ; Electron Transport Complex IV/*chemistry/metabolism ; Escherichia coli/metabolism ; Lipids/chemistry ; Magnetic Resonance Spectroscopy ; Models, Chemical ; Models, Molecular ; Protein Conformation ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*chemistry/metabolism ; }, abstract = {The Saccharomyces cerevisiae respiratory supercomplex factor 1 (Rcf1) protein is located in the mitochondrial inner membrane where it is involved in formation of supercomplexes composed of respiratory complexes III and IV. We report the solution structure of Rcf1, which forms a dimer in dodecylphosphocholine (DPC) micelles, where each monomer consists of a bundle of five transmembrane (TM) helices and a short flexible soluble helix (SH). Three TM helices are unusually charged and provide the dimerization interface consisting of 10 putative salt bridges, defining a "charge zipper" motif. The dimer structure is supported by molecular dynamics (MD) simulations in DPC, although the simulations show a more dynamic dimer interface than the NMR data. Furthermore, CD and NMR data indicate that Rcf1 undergoes a structural change when reconstituted in liposomes, which is supported by MD data, suggesting that the dimer structure is unstable in a planar membrane environment. Collectively, these data indicate a dynamic monomer-dimer equilibrium. Furthermore, the Rcf1 dimer interacts with cytochrome c, suggesting a role as an electron-transfer bridge between complexes III and IV. The Rcf1 structure will help in understanding its functional roles at a molecular level.}, } @article {pmid29507227, year = {2018}, author = {Kermani, AA and Macdonald, CB and Gundepudi, R and Stockbridge, RB}, title = {Guanidinium export is the primal function of SMR family transporters.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3060-3065}, pmid = {29507227}, issn = {1091-6490}, support = {R00 GM111767/GM/NIGMS NIH HHS/United States ; R35 GM128768/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Antiporters/chemistry/*metabolism ; Bacteria/chemistry/metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biological Transport ; Evolution, Molecular ; Guanidine/*metabolism ; Phylogeny ; Riboswitch ; }, abstract = {The small multidrug resistance (SMR) family of membrane proteins is prominent because of its rare dual topology architecture, simplicity, and small size. Its best studied member, EmrE, is an important model system in several fields related to membrane protein biology, from evolution to mechanism. But despite decades of work on these multidrug transporters, the native function of the SMR family has remained a mystery, and many highly similar SMR homologs do not transport drugs at all. Here we establish that representative SMR proteins, selected from each of the major clades in the phylogeny, function as guanidinium ion exporters. Drug-exporting SMRs are all clustered in a single minority clade. Using membrane transport experiments, we show that these guanidinium exporters, which we term Gdx, are very selective for guanidinium and strictly and stoichiometrically couple its export with the import of two protons. These findings draw important mechanistic distinctions with the notably promiscuous and weakly coupled drug exporters like EmrE.}, } @article {pmid29507226, year = {2018}, author = {Patzelt, T and Keppler, SJ and Gorka, O and Thoene, S and Wartewig, T and Reth, M and Förster, I and Lang, R and Buchner, M and Ruland, J}, title = {Foxp1 controls mature B cell survival and the development of follicular and B-1 B cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3120-3125}, pmid = {29507226}, issn = {1091-6490}, support = {322865//European Research Council/International ; }, mesh = {Animals ; Antibodies/metabolism ; Antigens, CD19/metabolism ; B-Lymphocytes/*classification/*physiology ; Forkhead Transcription Factors/genetics/*metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Oligonucleotide Array Sequence Analysis ; Polymerase Chain Reaction ; Repressor Proteins/genetics/*metabolism ; T-Lymphocytes/physiology ; bcl-X Protein/genetics/metabolism ; }, abstract = {The transcription factor Foxp1 is critical for early B cell development. Despite frequent deregulation of Foxp1 in B cell lymphoma, the physiological functions of Foxp1 in mature B cells remain unknown. Here, we used conditional gene targeting in the B cell lineage and report that Foxp1 disruption in developing and mature B cells results in reduced numbers and frequencies of follicular and B-1 B cells and in impaired antibody production upon T cell-independent immunization in vivo. Moreover, Foxp1-deficient B cells are impaired in survival even though they exhibit an increased capacity to proliferate. Transcriptional analysis identified defective expression of the prosurvival Bcl-2 family gene Bcl2l1 encoding Bcl-xl in Foxp1-deficient B cells, and we identified Foxp1 binding in the regulatory region of Bcl2l1 Transgenic overexpression of Bcl2 rescued the survival defect in Foxp1-deficient mature B cells in vivo and restored peripheral B cell numbers. Thus, our results identify Foxp1 as a physiological regulator of mature B cell survival mediated in part via the control of Bcl-xl expression and imply that this pathway might contribute to the pathogenic function of aberrant Foxp1 expression in lymphoma.}, } @article {pmid29507225, year = {2018}, author = {Lefcheck, JS and Orth, RJ and Dennison, WC and Wilcox, DJ and Murphy, RR and Keisman, J and Gurbisz, C and Hannam, M and Landry, JB and Moore, KA and Patrick, CJ and Testa, J and Weller, DE and Batiuk, RA}, title = {Long-term nutrient reductions lead to the unprecedented recovery of a temperate coastal region.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3658-3662}, pmid = {29507225}, issn = {1091-6490}, mesh = {Biodiversity ; Conservation of Natural Resources/*methods ; *Ecosystem ; Environmental Monitoring ; Estuaries ; *Eutrophication ; *Food ; Maryland ; Phytoplankton/*growth & development ; Water Pollutants, Chemical/*analysis ; Water Pollution/prevention & control ; }, abstract = {Humans strongly impact the dynamics of coastal systems, yet surprisingly few studies mechanistically link management of anthropogenic stressors and successful restoration of nearshore habitats over large spatial and temporal scales. Such examples are sorely needed to ensure the success of ecosystem restoration efforts worldwide. Here, we unite 30 consecutive years of watershed modeling, biogeochemical data, and comprehensive aerial surveys of Chesapeake Bay, United States to quantify the cascading effects of anthropogenic impacts on submersed aquatic vegetation (SAV), an ecologically and economically valuable habitat. We employ structural equation models to link land use change to higher nutrient loads, which in turn reduce SAV cover through multiple, independent pathways. We also show through our models that high biodiversity of SAV consistently promotes cover, an unexpected finding that corroborates emerging evidence from other terrestrial and marine systems. Due to sustained management actions that have reduced nitrogen concentrations in Chesapeake Bay by 23% since 1984, SAV has regained 17,000 ha to achieve its highest cover in almost half a century. Our study empirically demonstrates that nutrient reductions and biodiversity conservation are effective strategies to aid the successful recovery of degraded systems at regional scales, a finding which is highly relevant to the utility of environmental management programs worldwide.}, } @article {pmid29507224, year = {2018}, author = {Henriksson, PJG and Belton, B and Jahan, KM and Rico, A}, title = {Measuring the potential for sustainable intensification of aquaculture in Bangladesh using life cycle assessment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2958-2963}, pmid = {29507224}, issn = {1091-6490}, mesh = {Animals ; Aquaculture/*economics ; Bangladesh ; Benchmarking ; Commerce ; Environment ; Fishes/physiology ; Humans ; Models, Theoretical ; }, abstract = {Food production is a major driver of global environmental change and the overshoot of planetary sustainability boundaries. Greater affluence in developing nations and human population growth are also increasing demand for all foods, and for animal proteins in particular. Consequently, a growing body of literature calls for the sustainable intensification of food production, broadly defined as "producing more using less". Most assessments of the potential for sustainable intensification rely on only one or two indicators, meaning that ecological trade-offs among impact categories that occur as production intensifies may remain unaccounted for. The present study addresses this limitation using life cycle assessment (LCA) to quantify six local and global environmental consequences of intensifying aquaculture production in Bangladesh. Production data are from a unique survey of 2,678 farms, and results show multidirectional associations between the intensification of aquaculture production and its environmental impacts. Intensification (measured in material and economic output per unit primary area farmed) is positively correlated with acidification, eutrophication, and ecotoxicological impacts in aquatic ecosystems; negatively correlated with freshwater consumption; and indifferent with regard to global warming and land occupation. As production intensifies, the geographical locations of greenhouse gas (GHG) emissions, acidifying emissions, freshwater consumption, and land occupation shift from the immediate vicinity of the farm to more geographically dispersed telecoupled locations across the globe. Simple changes in fish farming technology and management practices that could help make the global transition to more intensive forms of aquaculture be more sustainable are identified.}, } @article {pmid29507223, year = {2018}, author = {Jeoung, JH and Dobbek, H}, title = {ATP-dependent substrate reduction at an [Fe8S9] double-cubane cluster.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2994-2999}, pmid = {29507223}, issn = {1091-6490}, mesh = {Acetylene/metabolism ; Adenosine Triphosphate/*metabolism ; Cloning, Molecular ; Firmicutes/metabolism ; Gene Expression Regulation, Bacterial ; Iron-Sulfur Proteins/*metabolism ; Models, Molecular ; Protein Conformation ; }, abstract = {Chemically demanding reductive conversions in biology, such as the reduction of dinitrogen to ammonia or the Birch-type reduction of aromatic compounds, depend on Fe/S-cluster-containing ATPases. These reductions are typically catalyzed by two-component systems, in which an Fe/S-cluster-containing ATPase energizes an electron to reduce a metal site on the acceptor protein that drives the reductive reaction. Here, we show a two-component system featuring a double-cubane [Fe8S9]-cluster [{Fe4S4(SCys)3}2(μ2-S)]. The double-cubane-cluster-containing enzyme is capable of reducing small molecules, such as acetylene (C2H2), azide (N3-), and hydrazine (N2H4). We thus present a class of metalloenzymes akin in fold, metal clusters, and reactivity to nitrogenases.}, } @article {pmid29507222, year = {2018}, author = {Yoo, YD and Mun, SR and Ji, CH and Sung, KW and Kang, KY and Heo, AJ and Lee, SH and An, JY and Hwang, J and Xie, XQ and Ciechanover, A and Kim, BY and Kwon, YT}, title = {N-terminal arginylation generates a bimodal degron that modulates autophagic proteolysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2716-E2724}, pmid = {29507222}, issn = {1091-6490}, support = {P30 DA035778/DA/NIDA NIH HHS/United States ; }, mesh = {Aminoacyltransferases/genetics/metabolism ; Animals ; Arginine/*metabolism ; Autophagy/drug effects/*physiology ; BRCA1 Protein/metabolism ; Cell Cycle Proteins/*metabolism ; Female ; HEK293 Cells ; HeLa Cells ; Humans ; Hydroxychloroquine/pharmacology ; Mice ; Mice, Inbred C57BL ; Nuclear Proteins/*metabolism ; Proteasome Endopeptidase Complex/metabolism ; Protein Domains ; *Proteolysis ; RNA-Binding Proteins/*metabolism ; Ubiquitin/metabolism ; }, abstract = {The conjugation of amino acids to the protein N termini is universally observed in eukaryotes and prokaryotes, yet its functions remain poorly understood. In eukaryotes, the amino acid l-arginine (l-Arg) is conjugated to N-terminal Asp (Nt-Asp), Glu, Gln, Asn, and Cys, directly or associated with posttranslational modifications. Following Nt-arginylation, the Nt-Arg is recognized by UBR boxes of N-recognins such as UBR1, UBR2, UBR4/p600, and UBR5/EDD, leading to substrate ubiquitination and proteasomal degradation via the N-end rule pathway. It has been a mystery, however, why studies for the past five decades identified only a handful of Nt-arginylated substrates in mammals, although five of 20 principal amino acids are eligible for arginylation. Here, we show that the Nt-Arg functions as a bimodal degron that directs substrates to either the ubiquitin (Ub)-proteasome system (UPS) or macroautophagy depending on physiological states. In normal conditions, the arginylated forms of proteolytic cleavage products, D101-CDC6 and D1156-BRCA1, are targeted to UBR box-containing N-recognins and degraded by the proteasome. However, when proteostasis by the UPS is perturbed, their Nt-Arg redirects these otherwise cellular wastes to macroautophagy through its binding to the ZZ domain of the autophagic adaptor p62/STQSM/Sequestosome-1. Upon binding to the Nt-Arg, p62 acts as an autophagic N-recognin that undergoes self-polymerization, facilitating cargo collection and lysosomal degradation of p62-cargo complexes. A chemical mimic of Nt-Arg redirects Ub-conjugated substrates from the UPS to macroautophagy and promotes their lysosomal degradation. Our results suggest that the Nt-Arg proteome of arginylated proteins contributes to reprogramming global proteolytic flux under stresses.}, } @article {pmid29507221, year = {2018}, author = {Zhang, L and Yuan, H and Meng, Y and Mao, HK}, title = {Discovery of a hexagonal ultradense hydrous phase in (Fe,Al)OOH.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2908-2911}, pmid = {29507221}, issn = {1091-6490}, abstract = {A deep lower-mantle (DLM) water reservoir depends on availability of hydrous minerals which can store and transport water into the DLM without dehydration. Recent discoveries found hydrous phases AlOOH (Z = 2) with a CaCl2-type structure and FeOOH (Z = 4) with a cubic pyrite-type structure stable under the high-pressure-temperature (P-T) conditions of the DLM. Our experiments at 107-136 GPa and 2,400 K have further demonstrated that (Fe,Al)OOH is stabilized in a hexagonal lattice. By combining powder X-ray-diffraction techniques with multigrain indexation, we are able to determine this hexagonal hydrous phase with a = 10.5803(6) Å and c = 2.5897(3) Å at 110 GPa. Hexagonal (Fe,Al)OOH can transform to the cubic pyrite structure at low T with the same density. The hexagonal phase can be formed when δ-AlOOH incorporates FeOOH produced by reaction between water and Fe, which may store a substantial quantity of water in the DLM.}, } @article {pmid29507220, year = {2018}, author = {Hall, GJ and Sargent, TJ}, title = {Brief history of US debt limits before 1939.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2942-2945}, doi = {10.1073/pnas.1719687115}, pmid = {29507220}, issn = {1091-6490}, abstract = {Between 1776 and 1920, the US Congress designed more than 200 distinct securities and stated the maximum amount of each that the Treasury could sell. Between 1917 and 1939, Congress gradually delegated all decisions about designing US debt instruments to the Treasury. In 1939, Congress began imposing a limit on the par value of total federal debt outstanding. By summing Congressional borrowing authorizations outstanding each year for each bond, we construct a time series of implied federal debt limits before 1939.}, } @article {pmid29507219, year = {2018}, author = {Liberal, I and Engheta, N}, title = {Manipulating thermal emission with spatially static fluctuating fields in arbitrarily shaped epsilon-near-zero bodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2878-2883}, pmid = {29507219}, issn = {1091-6490}, abstract = {The control and manipulation of thermal fields is a key scientific and technological challenge, usually addressed with nanophotonic structures with a carefully designed geometry. Here, we theoretically investigate a different strategy based on epsilon-near-zero (ENZ) media. We demonstrate that thermal emission from ENZ bodies is characterized by the excitation of spatially static fluctuating fields, which can be resonantly enhanced with the addition of dielectric particles. The "spatially static" character of these temporally dynamic fields leads to enhanced spatial coherence on the surface of the body, resulting in directive thermal emission. By contrast with other approaches, this property is intrinsic to ENZ media and it is not tied to its geometry. This point is illustrated with effects such as geometry-invariant resonant emission, beamforming by boundary deformation, and independence with respect to the position of internal particles. We numerically investigate a practical implementation based on a silicon carbide body containing a germanium rod.}, } @article {pmid29507218, year = {2018}, author = {Miao, Y and McCammon, JA}, title = {Mechanism of the G-protein mimetic nanobody binding to a muscarinic G-protein-coupled receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3036-3041}, pmid = {29507218}, issn = {1091-6490}, support = {R01 GM031749/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Computer Simulation ; Models, Molecular ; Protein Binding ; Protein Conformation ; Receptor, Muscarinic M2/chemistry/*metabolism ; Receptors, G-Protein-Coupled/chemistry/*metabolism ; Single-Domain Antibodies/*physiology ; Thermodynamics ; }, abstract = {Protein-protein binding is key in cellular signaling processes. Molecular dynamics (MD) simulations of protein-protein binding, however, are challenging due to limited timescales. In particular, binding of the medically important G-protein-coupled receptors (GPCRs) with intracellular signaling proteins has not been simulated with MD to date. Here, we report a successful simulation of the binding of a G-protein mimetic nanobody to the M2 muscarinic GPCR using the robust Gaussian accelerated MD (GaMD) method. Through long-timescale GaMD simulations over 4,500 ns, the nanobody was observed to bind the receptor intracellular G-protein-coupling site, with a minimum rmsd of 2.48 Å in the nanobody core domain compared with the X-ray structure. Binding of the nanobody allosterically closed the orthosteric ligand-binding pocket, being consistent with the recent experimental finding. In the absence of nanobody binding, the receptor orthosteric pocket sampled open and fully open conformations. The GaMD simulations revealed two low-energy intermediate states during nanobody binding to the M2 receptor. The flexible receptor intracellular loops contribute remarkable electrostatic, polar, and hydrophobic residue interactions in recognition and binding of the nanobody. These simulations provided important insights into the mechanism of GPCR-nanobody binding and demonstrated the applicability of GaMD in modeling dynamic protein-protein interactions.}, } @article {pmid29507217, year = {2018}, author = {Lanaspa, MA and Kuwabara, M and Andres-Hernando, A and Li, N and Cicerchi, C and Jensen, T and Orlicky, DJ and Roncal-Jimenez, CA and Ishimoto, T and Nakagawa, T and Rodriguez-Iturbe, B and MacLean, PS and Johnson, RJ}, title = {High salt intake causes leptin resistance and obesity in mice by stimulating endogenous fructose production and metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3138-3143}, pmid = {29507217}, issn = {1091-6490}, support = {P30 DK048520/DK/NIDDK NIH HHS/United States ; R03 DK105041/DK/NIDDK NIH HHS/United States ; R01 DK108408/DK/NIDDK NIH HHS/United States ; P50 HD073063/HD/NICHD NIH HHS/United States ; R01 DK109408/DK/NIDDK NIH HHS/United States ; R01 DK108859/DK/NIDDK NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Animals ; Diabetes Mellitus/chemically induced ; Fructokinases/genetics ; Fructose/*metabolism ; Humans ; Leptin/*blood/genetics ; Metabolic Syndrome/chemically induced/genetics ; Mice, Inbred C57BL ; Mice, Knockout ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*chemically induced ; Obesity/*chemically induced/metabolism ; Sodium Chloride, Dietary/*adverse effects ; Sucrose/adverse effects/analogs & derivatives ; Transcription Factors/genetics/metabolism ; }, abstract = {Dietary guidelines for obesity typically focus on three food groups (carbohydrates, fat, and protein) and caloric restriction. Intake of noncaloric nutrients, such as salt, are rarely discussed. However, recently high salt intake has been reported to predict the development of obesity and insulin resistance. The mechanism for this effect is unknown. Here we show that high intake of salt activates the aldose reductase-fructokinase pathway in the liver and hypothalamus, leading to endogenous fructose production with the development of leptin resistance and hyperphagia that cause obesity, insulin resistance, and fatty liver. A high-salt diet was also found to predict the development of diabetes and nonalcoholic fatty liver disease in a healthy population. These studies provide insights into the pathogenesis of obesity and diabetes and raise the potential for reduction in salt intake as an additional interventional approach for reducing the risk for developing obesity and metabolic syndrome.}, } @article {pmid29507216, year = {2018}, author = {Rogne, P and Rosselin, M and Grundström, C and Hedberg, C and Sauer, UH and Wolf-Watz, M}, title = {Molecular mechanism of ATP versus GTP selectivity of adenylate kinase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3012-3017}, pmid = {29507216}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/*metabolism ; Adenylyl Cyclase Inhibitors/chemistry/pharmacology ; Adenylyl Cyclases/*metabolism ; Guanosine Triphosphate/*metabolism ; Inosine Triphosphate/genetics/metabolism ; Kinetics ; Models, Molecular ; Protein Conformation ; Structure-Activity Relationship ; Substrate Specificity ; }, abstract = {Enzymatic substrate selectivity is critical for the precise control of metabolic pathways. In cases where chemically related substrates are present inside cells, robust mechanisms of substrate selectivity are required. Here, we report the mechanism utilized for catalytic ATP versus GTP selectivity during adenylate kinase (Adk) -mediated phosphorylation of AMP. Using NMR spectroscopy we found that while Adk adopts a catalytically competent and closed structural state in complex with ATP, the enzyme is arrested in a catalytically inhibited and open state in complex with GTP. X-ray crystallography experiments revealed that the interaction interfaces supporting ATP and GTP recognition, in part, are mediated by coinciding residues. The mechanism provides an atomic view on how the cellular GTP pool is protected from Adk turnover, which is important because GTP has many specialized cellular functions. In further support of this mechanism, a structure-function analysis enabled by synthesis of ATP analogs suggests that a hydrogen bond between the adenine moiety and the backbone of the enzyme is vital for ATP selectivity. The importance of the hydrogen bond for substrate selectivity is likely general given the conservation of its location and orientation across the family of eukaryotic protein kinases.}, } @article {pmid29507215, year = {2018}, author = {Fan, Y and Cross, PJ and Jameson, GB and Parker, EJ}, title = {Exploring modular allostery via interchangeable regulatory domains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3006-3011}, pmid = {29507215}, issn = {1091-6490}, mesh = {3-Deoxy-7-Phosphoheptulonate Synthase/chemistry/genetics/*metabolism ; Allosteric Regulation ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Enzymologic ; Protein Domains ; Thermotoga maritima/genetics/*metabolism ; }, abstract = {Most proteins comprise two or more domains from a limited suite of protein families. These domains are often rearranged in various combinations through gene fusion events to evolve new protein functions, including the acquisition of protein allostery through the incorporation of regulatory domains. The enzyme 3-deoxy-d-arabino-heptulosonate 7-phosphate synthase (DAH7PS) is the first enzyme of aromatic amino acid biosynthesis and displays a diverse range of allosteric mechanisms. DAH7PSs adopt a common architecture with a shared (β/α)8 catalytic domain which can be attached to an ACT-like or a chorismate mutase regulatory domain that operates via distinct mechanisms. These respective domains confer allosteric regulation by controlling DAH7PS function in response to ligand Tyr or prephenate. Starting with contemporary DAH7PS proteins, two protein chimeras were created, with interchanged regulatory domains. Both engineered proteins were catalytically active and delivered new functional allostery with switched ligand specificity and allosteric mechanisms delivered by their nonhomologous regulatory domains. This interchangeability of protein domains represents an efficient method not only to engineer allostery in multidomain proteins but to create a new bifunctional enzyme.}, } @article {pmid29507214, year = {2018}, author = {Lu, Z and Liu, X and Zhang, Z and Zhao, C and Meyer, K and Rajapakshe, C and Wu, C and Yang, Z and Penner, JE}, title = {Biomass smoke from southern Africa can significantly enhance the brightness of stratocumulus over the southeastern Atlantic Ocean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2924-2929}, pmid = {29507214}, issn = {1091-6490}, mesh = {Aerosols ; Africa, Southern ; *Air Pollutants ; Atlantic Ocean ; *Atmosphere ; *Biomass ; *Smoke ; *Sunlight ; }, abstract = {Marine stratocumulus clouds cover nearly one-quarter of the ocean surface and thus play an extremely important role in determining the global radiative balance. The semipermanent marine stratocumulus deck over the southeastern Atlantic Ocean is of particular interest, because of its interactions with seasonal biomass burning aerosols that are emitted in southern Africa. Understanding the impacts of biomass burning aerosols on stratocumulus clouds and the implications for regional and global radiative balance is still very limited. Previous studies have focused on assessing the magnitude of the warming caused by solar scattering and absorption by biomass burning aerosols over stratocumulus (the direct radiative effect) or cloud adjustments to the direct radiative effect (the semidirect effect). Here, using a nested modeling approach in conjunction with observations from multiple satellites, we demonstrate that cloud condensation nuclei activated from biomass burning aerosols entrained into the stratocumulus (the microphysical effect) can play a dominant role in determining the total radiative forcing at the top of the atmosphere, compared with their direct and semidirect radiative effects. Biomass burning aerosols over the region and period with heavy loadings can cause a substantial cooling (daily mean -8.05 W m-2), primarily as a result of clouds brightening by reducing the cloud droplet size (the Twomey effect) and secondarily through modulating the diurnal cycle of cloud liquid water path and coverage (the cloud lifetime effect). Our results highlight the importance of realistically representing the interactions of stratocumulus with biomass burning aerosols in global climate models in this region.}, } @article {pmid29507213, year = {2018}, author = {Cai, Y and Tang, X and Chen, X and Li, X and Wang, Y and Bao, X and Wang, L and Sun, D and Zhao, J and Xing, Y and Warner, M and Xu, H and Gustafsson, JÅ and Fan, X}, title = {Liver X receptor β regulates the development of the dentate gyrus and autistic-like behavior in the mouse.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2725-E2733}, pmid = {29507213}, issn = {1091-6490}, mesh = {Animals ; Autistic Disorder/*etiology/genetics ; Behavior, Animal/physiology ; Cell Differentiation ; Cell Proliferation/genetics ; Dentate Gyrus/cytology/*growth & development/metabolism ; Fatty Acid-Binding Protein 7/metabolism ; Female ; Gene Expression Regulation, Developmental ; Liver X Receptors/genetics/*metabolism ; Male ; Mice, Knockout ; Neuroglia/cytology ; Neurons/*pathology/physiology ; Receptor, Notch1/metabolism ; Stem Cells/cytology/physiology ; }, abstract = {The dentate gyrus (DG) of the hippocampus is a laminated brain region in which neurogenesis begins during early embryonic development and continues until adulthood. Recent studies have implicated that defects in the neurogenesis of the DG seem to be involved in the genesis of autism spectrum disorders (ASD)-like behaviors. Liver X receptor β (LXRβ) has recently emerged as an important transcription factor involved in the development of laminated CNS structures, but little is known about its role in the development of the DG. Here, we show that deletion of the LXRβ in mice causes hypoplasia in the DG, including abnormalities in the formation of progenitor cells and granule cell differentiation. We also found that expression of Notch1, a central mediator of progenitor cell self-renewal, is reduced in LXRβ-null mice. In addition, LXRβ deletion in mice results in autistic-like behaviors, including abnormal social interaction and repetitive behavior. These data reveal a central role for LXRβ in orchestrating the timely differentiation of neural progenitor cells within the DG, thereby providing a likely explanation for its association with the genesis of autism-related behaviors in LXRβ-deficient mice.}, } @article {pmid29507212, year = {2018}, author = {Yadav, V and Sun, S and Billmyre, RB and Thimmappa, BC and Shea, T and Lintner, R and Bakkeren, G and Cuomo, CA and Heitman, J and Sanyal, K}, title = {RNAi is a critical determinant of centromere evolution in closely related fungi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3108-3113}, pmid = {29507212}, issn = {1091-6490}, support = {R01 AI039115/AI/NIAID NIH HHS/United States ; R01 AI050113/AI/NIAID NIH HHS/United States ; R37 AI039115/AI/NIAID NIH HHS/United States ; U19 AI110818/AI/NIAID NIH HHS/United States ; }, mesh = {Base Sequence ; Centromere/*genetics ; Chromosomes, Fungal/genetics ; Cryptococcus/*genetics ; DNA, Fungal/*genetics ; *Evolution, Molecular ; *RNA Interference ; }, abstract = {The centromere DNA locus on a eukaryotic chromosome facilitates faithful chromosome segregation. Despite performing such a conserved function, centromere DNA sequence as well as the organization of sequence elements is rapidly evolving in all forms of eukaryotes. The driving force that facilitates centromere evolution remains an enigma. Here, we studied the evolution of centromeres in closely related species in the fungal phylum of Basidiomycota. Using ChIP-seq analysis of conserved inner kinetochore proteins, we identified centromeres in three closely related Cryptococcus species: two of which are RNAi-proficient, while the other lost functional RNAi. We find that the centromeres in the RNAi-deficient species are significantly shorter than those of the two RNAi-proficient species. While centromeres are LTR retrotransposon-rich in all cases, the RNAi-deficient species lost all full-length retroelements from its centromeres. In addition, centromeres in RNAi-proficient species are associated with a significantly higher level of cytosine DNA modifications compared with those of RNAi-deficient species. Furthermore, when an RNAi-proficient Cryptococcus species and its RNAi-deficient mutants were passaged under similar conditions, the centromere length was found to be occasionally shortened in RNAi mutants. In silico analysis of predicted centromeres in a group of closely related Ustilago species, also belonging to the Basidiomycota, were found to have undergone a similar transition in the centromere length in an RNAi-dependent fashion. Based on the correlation found in two independent basidiomycetous species complexes, we present evidence suggesting that the loss of RNAi and cytosine DNA methylation triggered transposon attrition, which resulted in shortening of centromere length during evolution.}, } @article {pmid29507211, year = {2018}, author = {Meng, D and Guo, H and Cui, Z and Ma, C and Zhao, J and Lu, J and Xu, H and Wang, Z and Hu, X and Fu, Z and Peng, R and Guo, J and Zhai, X and Brown, GJ and Knize, R and Lu, Y}, title = {Strain-induced high-temperature perovskite ferromagnetic insulator.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2873-2877}, pmid = {29507211}, issn = {1091-6490}, abstract = {Ferromagnetic insulators are required for many new magnetic devices, such as dissipationless quantum-spintronic devices, magnetic tunneling junctions, etc. Ferromagnetic insulators with a high Curie temperature and a high-symmetry structure are critical integration with common single-crystalline oxide films or substrates. So far, the commonly used ferromagnetic insulators mostly possess low-symmetry structures associated with a poor growth quality and widespread properties. The few known high-symmetry materials either have extremely low Curie temperatures (≤16 K), or require chemical doping of an otherwise antiferromagnetic matrix. Here we present compelling evidence that the LaCoO3 single-crystalline thin film under tensile strain is a rare undoped perovskite ferromagnetic insulator with a remarkably high TC of up to 90 K. Both experiments and first-principles calculations demonstrate tensile-strain-induced ferromagnetism which does not exist in bulk LaCoO3 The ferromagnetism is strongest within a nearly stoichiometric structure, disappearing when the Co2+ defect concentration reaches about 10%. Significant impact of the research includes demonstration of a strain-induced high-temperature ferromagnetic insulator, successful elevation of the transition over the liquid-nitrogen temperature, and high potential for integration into large-area device fabrication processes.}, } @article {pmid29507210, year = {2018}, author = {Greene, NG and Fumeaux, C and Bernhardt, TG}, title = {Conserved mechanism of cell-wall synthase regulation revealed by the identification of a new PBP activator in Pseudomonas aeruginosa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3150-3155}, pmid = {29507210}, issn = {1091-6490}, support = {171535//Swiss National Science Foundation/Switzerland ; R01 AI083365/AI/NIAID NIH HHS/United States ; R33 AI111713/AI/NIAID NIH HHS/United States ; }, mesh = {Acinetobacter/chemistry ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Cell Wall/metabolism ; DNA Transposable Elements ; Escherichia coli/genetics/metabolism ; Gene Expression Regulation, Bacterial ; Lipoproteins/chemistry/genetics/metabolism ; Mutation ; Penicillin-Binding Proteins/chemistry/genetics/*metabolism ; Phylogeny ; Pseudomonas aeruginosa/cytology/genetics/*metabolism ; }, abstract = {Penicillin-binding proteins (PBPs) are synthases required to build the essential peptidoglycan (PG) cell wall surrounding most bacterial cells. The mechanisms regulating the activity of these enzymes to control PG synthesis remain surprisingly poorly defined given their status as key antibiotic targets. Several years ago, the outer-membrane lipoprotein EcLpoB was identified as a critical activator of Escherichia coli PBP1b (EcPBP1b), one of the major PG synthases of this organism. Activation of EcPBP1b is mediated through the association of EcLpoB with a regulatory domain on EcPBP1b called UB2H. Notably, Pseudomonas aeruginosa also encodes PBP1b (PaPBP1b), which possesses a UB2H domain, but this bacterium lacks an identifiable LpoB homolog. We therefore searched for potential PaPBP1b activators and identified a lipoprotein unrelated to LpoB that is required for the in vivo activity of PaPBP1b. We named this protein LpoP and found that it interacts directly with PaPBP1b in vitro and is conserved in many Gram-negative species. Importantly, we also demonstrated that PaLpoP-PaPBP1b as well as an equivalent protein pair from Acinetobacter baylyi can fully substitute for EcLpoB-EcPBP1b in E. coli for PG synthesis. Furthermore, we show that amino acid changes in PaPBP1b that bypass the PaLpoP requirement map to similar locations in the protein as changes promoting EcLpoB bypass in EcPBP1b. Overall, our results indicate that, although different Gram-negative bacteria activate their PBP1b synthases with distinct lipoproteins, they stimulate the activity of these important drug targets using a conserved mechanism.}, } @article {pmid29507209, year = {2018}, author = {Disselhorst, JA and Krueger, MA and Ud-Dean, SMM and Bezrukov, I and Jarboui, MA and Trautwein, C and Traube, A and Spindler, C and Cotton, JM and Leibfritz, D and Pichler, BJ}, title = {Linking imaging to omics utilizing image-guided tissue extraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2980-E2987}, pmid = {29507209}, issn = {1091-6490}, support = {323196//European Research Council/International ; }, mesh = {Animals ; Female ; Genetic Heterogeneity ; Genomics ; Image Processing, Computer-Assisted/*methods ; Kidney Tubules/chemistry/*diagnostic imaging/metabolism ; Magnetic Resonance Imaging/*methods ; Metabolomics ; Myocardium/*chemistry/metabolism ; Positron-Emission Tomography/*methods ; Proteomics ; RNA/genetics/isolation & purification/metabolism ; Tissue Extracts/chemistry/*isolation & purification ; Tomography, X-Ray Computed/*methods ; }, abstract = {Phenotypic heterogeneity is commonly observed in diseased tissue, specifically in tumors. Multimodal imaging technologies can reveal tissue heterogeneity noninvasively in vivo, enabling imaging-based profiling of receptors, metabolism, morphology, or function on a macroscopic scale. In contrast, in vitro multiomics, immunohistochemistry, or histology techniques accurately characterize these heterogeneities in the cellular and subcellular scales in a more comprehensive but ex vivo manner. The complementary in vivo and ex vivo information would provide an enormous potential to better characterize a disease. However, this requires spatially accurate coregistration of these data by image-driven sampling as well as fast sample-preparation methods. Here, a unique image-guided milling machine and workflow for precise extraction of tissue samples from small laboratory animals or excised organs has been developed and evaluated. The samples can be delineated on tomographic images as volumes of interest and can be extracted with a spatial accuracy better than 0.25 mm. The samples remain cooled throughout the procedure to ensure metabolic stability, a precondition for accurate in vitro analysis.}, } @article {pmid29507208, year = {2018}, author = {Calisi, RM and , }, title = {Opinion: How to tackle the childcare-conference conundrum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2845-2849}, pmid = {29507208}, issn = {1091-6490}, mesh = {Career Mobility ; Child ; *Child Care ; Congresses as Topic/*organization & administration ; Female ; Humans ; Science/*organization & administration ; Societies ; }, } @article {pmid29507207, year = {2018}, author = {Qi, S and Hassabis, D and Sun, J and Guo, F and Daw, N and Mobbs, D}, title = {How cognitive and reactive fear circuits optimize escape decisions in humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3186-3191}, pmid = {29507207}, issn = {1091-6490}, support = {P50 MH094258/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Animals ; Bayes Theorem ; Brain/physiology ; Escape Reaction/*physiology ; Fear/*physiology/psychology ; Female ; Humans ; Male ; Models, Neurological ; Nontherapeutic Human Experimentation ; Predatory Behavior ; }, abstract = {Flight initiation distance (FID), the distance at which an organism flees from an approaching threat, is an ecological metric of cost-benefit functions of escape decisions. We adapted the FID paradigm to investigate how fast- or slow-attacking "virtual predators" constrain escape decisions. We show that rapid escape decisions rely on "reactive fear" circuits in the periaqueductal gray and midcingulate cortex (MCC), while protracted escape decisions, defined by larger buffer zones, were associated with "cognitive fear" circuits, which include posterior cingulate cortex, hippocampus, and the ventromedial prefrontal cortex, circuits implicated in more complex information processing, cognitive avoidance strategies, and behavioral flexibility. Using a Bayesian decision-making model, we further show that optimization of escape decisions under rapid flight were localized to the MCC, a region involved in adaptive motor control, while the hippocampus is implicated in optimizing decisions that update and control slower escape initiation. These results demonstrate an unexplored link between defensive survival circuits and their role in adaptive escape decisions.}, } @article {pmid29507206, year = {2018}, author = {Noh, S and Geist, KS and Tian, X and Strassmann, JE and Queller, DC}, title = {Genetic signatures of microbial altruism and cheating in social amoebas in the wild.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3096-3101}, pmid = {29507206}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; Dictyostelium/*genetics/*physiology ; Evolution, Molecular ; Gene Expression Regulation ; Genetic Variation ; Genome, Protozoan ; Selection, Genetic ; }, abstract = {Many microbes engage in social interactions. Some of these have come to play an important role in the study of cooperation and conflict, largely because, unlike most animals, they can be genetically manipulated and experimentally evolved. However, whereas animal social behavior can be observed and assessed in natural environments, microbes usually cannot, so we know little about microbial social adaptations in nature. This has led to some difficult-to-resolve controversies about social adaptation even for well-studied traits such as bacterial quorum sensing, siderophore production, and biofilms. Here we use molecular signatures of population genetics and molecular evolution to address controversies over the existence of altruism and cheating in social amoebas. First, we find signatures of rapid adaptive molecular evolution that are consistent with social conflict being a significant force in nature. Second, we find population-genetic signatures of purifying selection to support the hypothesis that the cells that form the sterile stalk evolve primarily through altruistic kin selection rather than through selfish direct reproduction. Our results show how molecular signatures can provide insight into social adaptations that cannot be observed in their natural context, and they support the hypotheses that social amoebas in the wild are both altruists and cheaters.}, } @article {pmid29507205, year = {2018}, author = {Cingöz, O and Goff, SP}, title = {Cyclin-dependent kinase activity is required for type I interferon production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {E2950-E2959}, pmid = {29507205}, issn = {1091-6490}, support = {R01 CA030488/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Antiviral Agents/*pharmacology ; Cells, Cultured ; Cyclin-Dependent Kinases/genetics/*metabolism ; Humans ; Immunity, Innate/drug effects/*immunology ; Interferon-alpha/*pharmacology ; Interferon-beta/*pharmacology ; Phosphorylation/drug effects ; STAT1 Transcription Factor/genetics/metabolism ; Signal Transduction/drug effects ; }, abstract = {Recognition of nucleic acids results in the production of type I IFNs, which activate the JAK/STAT pathway and promote the expression of IFN-stimulated genes. In a search for modulators of this pathway, we discovered an unexpected requirement for cyclin-dependent kinases (CDK) in the production of type I IFN following nucleic acid sensing and virus infection. Inhibition of CDK activity or knockdown of CDK levels leads to a striking block in STAT activation and IFN-stimulated gene expression. CDKs are not required for the initial nucleic acid sensing leading to IFN-β mRNA induction, nor for the response to exogenous IFN-α/β, but are critical for IFN-β release into culture supernatants, suggesting a posttranscriptional role for CDKs in type I IFN production. In the absence of CDK activity, we demonstrate a translational block specific for IFN-β, in which IFN-β mRNA is removed from the actively translating polysomes, while the distribution of other cellular mRNAs or global translation rates are unaffected. Our findings reveal a critical role for CDKs in the translation of IFN-β.}, } @article {pmid29507204, year = {2018}, author = {Zwicker, D and Ostilla-Mónico, R and Lieberman, DE and Brenner, MP}, title = {Physical and geometric constraints shape the labyrinth-like nasal cavity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2936-2941}, pmid = {29507204}, issn = {1091-6490}, mesh = {Animals ; Computer Simulation ; Humans ; Models, Biological ; Nasal Cavity/*anatomy & histology ; Respiratory Physiological Phenomena ; }, abstract = {The nasal cavity is a vital component of the respiratory system that heats and humidifies inhaled air in all vertebrates. Despite this common function, the shapes of nasal cavities vary widely across animals. To understand this variability, we here connect nasal geometry to its function by theoretically studying the airflow and the associated scalar exchange that describes heating and humidification. We find that optimal geometries, which have minimal resistance for a given exchange efficiency, have a constant gap width between their side walls, while their overall shape can adhere to the geometric constraints imposed by the head. Our theory explains the geometric variations of natural nasal cavities quantitatively, and we hypothesize that the trade-off between high exchange efficiency and low resistance to airflow is the main driving force shaping the nasal cavity. Our model further explains why humans, whose nasal cavities evolved to be smaller than expected for their size, become obligate oral breathers in aerobically challenging situations.}, } @article {pmid29507203, year = {2018}, author = {Mahanta, N and Liu, A and Dong, S and Nair, SK and Mitchell, DA}, title = {Enzymatic reconstitution of ribosomal peptide backbone thioamidation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3030-3035}, pmid = {29507203}, issn = {1091-6490}, support = {R01 GM079038/GM/NIGMS NIH HHS/United States ; R01 GM097142/GM/NIGMS NIH HHS/United States ; }, mesh = {Archaea/genetics/*metabolism ; Archaeal Proteins/genetics/*metabolism ; Computational Biology ; Gene Expression Regulation, Archaeal/physiology ; Methane/*biosynthesis ; Models, Molecular ; Protein Conformation ; Ribosomal Proteins/genetics/*metabolism ; Thioamides/chemistry/*metabolism ; }, abstract = {Methyl-coenzyme M reductase (MCR) is an essential enzyme found strictly in methanogenic and methanotrophic archaea. MCR catalyzes a reversible reaction involved in the production and consumption of the potent greenhouse gas methane. The α-subunit of this enzyme (McrA) contains several unusual posttranslational modifications, including the only known naturally occurring example of protein thioamidation. We have recently demonstrated by genetic deletion and mass spectrometry that the tfuA and ycaO genes of Methanosarcina acetivorans are involved in thioamidation of Gly465 in the MCR active site. Modification to thioGly has been postulated to stabilize the active site structure of MCR. Herein, we report the in vitro reconstitution of ribosomal peptide thioamidation using heterologously expressed and purified YcaO and TfuA proteins from M. acetivorans Like other reported YcaO proteins, this reaction is ATP-dependent but requires an external sulfide source. We also reconstitute the thioamidation activity of two TfuA-independent YcaOs from the hyperthermophilic methanogenic archaea Methanopyrus kandleri and Methanocaldococcus jannaschii Using these proteins, we demonstrate the basis for substrate recognition and regioselectivity of thioamide formation based on extensive mutagenesis, biochemical, and binding studies. Finally, we report nucleotide-free and nucleotide-bound crystal structures for the YcaO proteins from M. kandleri Sequence and structure-guided mutagenesis with subsequent biochemical evaluation have allowed us to assign roles for residues involved in thioamidation and confirm that the reaction proceeds via backbone O-phosphorylation. These data assign a new biochemical reaction to the YcaO superfamily and paves the way for further characterization of additional peptide backbone posttranslational modifications.}, } @article {pmid29507202, year = {2018}, author = {Liu, Y and Gonen, S and Gonen, T and Yeates, TO}, title = {Near-atomic cryo-EM imaging of a small protein displayed on a designed scaffolding system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3362-3367}, pmid = {29507202}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cryoelectron Microscopy/*methods ; Crystallography, X-Ray/*methods ; Macromolecular Substances/*ultrastructure ; Models, Molecular ; Protein Conformation ; Proteins/*ultrastructure ; }, abstract = {Current single-particle cryo-electron microscopy (cryo-EM) techniques can produce images of large protein assemblies and macromolecular complexes at atomic level detail without the need for crystal growth. However, proteins of smaller size, typical of those found throughout the cell, are not presently amenable to detailed structural elucidation by cryo-EM. Here we use protein design to create a modular, symmetrical scaffolding system to make protein molecules of typical size suitable for cryo-EM. Using a rigid continuous alpha helical linker, we connect a small 17-kDa protein (DARPin) to a protein subunit that was designed to self-assemble into a cage with cubic symmetry. We show that the resulting construct is amenable to structural analysis by single-particle cryo-EM, allowing us to identify and solve the structure of the attached small protein at near-atomic detail, ranging from 3.5- to 5-Å resolution. The result demonstrates that proteins considerably smaller than the theoretical limit of 50 kDa for cryo-EM can be visualized clearly when arrayed in a rigid fashion on a symmetric designed protein scaffold. Furthermore, because the amino acid sequence of a DARPin can be chosen to confer tight binding to various other protein or nucleic acid molecules, the system provides a future route for imaging diverse macromolecules, potentially broadening the application of cryo-EM to proteins of typical size in the cell.}, } @article {pmid29507201, year = {2018}, author = {Garcia, KE and Robinson, EC and Alexopoulos, D and Dierker, DL and Glasser, MF and Coalson, TS and Ortinau, CM and Rueckert, D and Taber, LA and Van Essen, DC and Rogers, CE and Smyser, CD and Bayly, PV}, title = {Dynamic patterns of cortical expansion during folding of the preterm human brain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3156-3161}, pmid = {29507201}, issn = {1091-6490}, support = {F30 MH097312/MH/NIMH NIH HHS/United States ; R01 NS055951/NS/NINDS NIH HHS/United States ; P30 HD062171/HD/NICHD NIH HHS/United States ; R01 MH060974/MH/NIMH NIH HHS/United States ; 319456//European Research Council/International ; K02 NS089852/NS/NINDS NIH HHS/United States ; U54 HD087011/HD/NICHD NIH HHS/United States ; K23 MH105179/MH/NIMH NIH HHS/United States ; UL1 TR000448/TR/NCATS NIH HHS/United States ; R01 NS070918/NS/NINDS NIH HHS/United States ; R01 HD057098/HD/NICHD NIH HHS/United States ; T32 EB018266/EB/NIBIB NIH HHS/United States ; UL1 TR002345/TR/NCATS NIH HHS/United States ; }, mesh = {Cerebral Cortex/abnormalities/*diagnostic imaging/*growth & development ; Female ; Humans ; Image Processing, Computer-Assisted/methods ; Infant, Premature ; Magnetic Resonance Imaging/methods ; Male ; }, abstract = {During the third trimester of human brain development, the cerebral cortex undergoes dramatic surface expansion and folding. Physical models suggest that relatively rapid growth of the cortical gray matter helps drive this folding, and structural data suggest that growth may vary in both space (by region on the cortical surface) and time. In this study, we propose a unique method to estimate local growth from sequential cortical reconstructions. Using anatomically constrained multimodal surface matching (aMSM), we obtain accurate, physically guided point correspondence between younger and older cortical reconstructions of the same individual. From each pair of surfaces, we calculate continuous, smooth maps of cortical expansion with unprecedented precision. By considering 30 preterm infants scanned two to four times during the period of rapid cortical expansion (28-38 wk postmenstrual age), we observe significant regional differences in growth across the cortical surface that are consistent with the emergence of new folds. Furthermore, these growth patterns shift over the course of development, with noninjured subjects following a highly consistent trajectory. This information provides a detailed picture of dynamic changes in cortical growth, connecting what is known about patterns of development at the microscopic (cellular) and macroscopic (folding) scales. Since our method provides specific growth maps for individual brains, we are also able to detect alterations due to injury. This fully automated surface analysis, based on tools freely available to the brain-mapping community, may also serve as a useful approach for future studies of abnormal growth due to genetic disorders, injury, or other environmental variables.}, } @article {pmid29507200, year = {2018}, author = {Chang, CJ and Jazayeri, M}, title = {Integration of speed and time for estimating time to contact.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2879-E2887}, pmid = {29507200}, issn = {1091-6490}, mesh = {Bayes Theorem ; Brain/*physiology ; Cues ; Humans ; *Models, Neurological ; Motion Perception ; Nontherapeutic Human Experimentation ; Psychophysics/*methods ; Time Perception/*physiology ; }, abstract = {To coordinate movements with events in a dynamic environment the brain has to anticipate when those events occur. A classic example is the estimation of time to contact (TTC), that is, when an object reaches a target. It is thought that TTC is estimated from kinematic variables. For example, a tennis player might use an estimate of distance (d) and speed (v) to estimate TTC (TTC = d/v). However, the tennis player may instead estimate TTC as twice the time it takes for the ball to move from the serve line to the net line. This latter strategy does not rely on kinematics and instead computes TTC solely from temporal cues. Which of these two strategies do humans use to estimate TTC? Considering that both speed and time estimates are inherently uncertain and the ability of the human brain to combine different sources of information, we hypothesized that humans estimate TTC by integrating speed information with temporal cues. We evaluated this hypothesis systematically using psychophysics and Bayesian modeling. Results indicated that humans rely on both speed information and temporal cues and integrate them to optimize their TTC estimates when both cues are present. These findings suggest that the brain's timing mechanisms are actively engaged when interacting with dynamic stimuli.}, } @article {pmid29507199, year = {2018}, author = {Marshall, J and Zhou, XZ and Chen, G and Yang, SQ and Li, Y and Wang, Y and Zhang, ZQ and Jiang, Q and Birnbaumer, L and Cao, C}, title = {Antidepression action of BDNF requires and is mimicked by Gαi1/3 expression in the hippocampus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {15}, pages = {E3549-E3558}, pmid = {29507199}, issn = {1091-6490}, support = {R01 NS094440/NS/NINDS NIH HHS/United States ; R21 MH104252/MH/NIMH NIH HHS/United States ; Z01 ES101643/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Brain-Derived Neurotrophic Factor/*metabolism ; Dendrites/metabolism/pathology ; Dendritic Spines/metabolism/pathology ; Depression/*metabolism/pathology ; Depressive Disorder, Major/metabolism/pathology ; Down-Regulation ; Female ; GTP-Binding Protein alpha Subunit, Gi2/*biosynthesis/genetics/metabolism ; GTP-Binding Protein alpha Subunits, Gi-Go/*biosynthesis/genetics/metabolism ; Hippocampus/*metabolism ; Mice ; Mice, Knockout ; Neurons/metabolism/pathology ; Signal Transduction/drug effects ; Stress, Physiological/physiology ; }, abstract = {Stress-related alterations in brain-derived neurotrophic factor (BDNF) expression, a neurotrophin that plays a key role in synaptic plasticity, are believed to contribute to the pathophysiology of depression. Here, we show that in a chronic mild stress (CMS) model of depression the Gαi1 and Gαi3 subunits of heterotrimeric G proteins are down-regulated in the hippocampus, a key limbic structure associated with major depressive disorder. We provide evidence that Gαi1 and Gαi3 (Gαi1/3) are required for the activation of TrkB downstream signaling pathways. In mouse embryonic fibroblasts (MEFs) and CNS neurons, Gαi1/3 knockdown inhibited BDNF-induced tropomyosin-related kinase B (TrkB) endocytosis, adaptor protein activation, and Akt-mTORC1 and Erk-MAPK signaling. Functional studies show that Gαi1 and Gαi3 knockdown decreases the number of dendrites and dendritic spines in hippocampal neurons. In vivo, hippocampal Gαi1/3 knockdown after bilateral microinjection of lentiviral constructs containing Gαi1 and Gαi3 shRNA elicited depressive behaviors. Critically, exogenous expression of Gαi3 in the hippocampus reversed depressive behaviors in CMS mice. Similar results were observed in Gαi1/Gαi3 double-knockout mice, which exhibited severe depressive behaviors. These results demonstrate that heterotrimeric Gαi1 and Gαi3 proteins are essential for TrkB signaling and that disruption of Gαi1 or Gαi3 function could contribute to depressive behaviors.}, } @article {pmid29507198, year = {2018}, author = {Guziewicz, KE and Cideciyan, AV and Beltran, WA and Komáromy, AM and Dufour, VL and Swider, M and Iwabe, S and Sumaroka, A and Kendrick, BT and Ruthel, G and Chiodo, VA and Héon, E and Hauswirth, WW and Jacobson, SG and Aguirre, GD}, title = {BEST1 gene therapy corrects a diffuse retina-wide microdetachment modulated by light exposure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2839-E2848}, pmid = {29507198}, issn = {1091-6490}, support = {R01 EY006855/EY/NEI NIH HHS/United States ; R01 EY019304/EY/NEI NIH HHS/United States ; S10 RR027128/RR/NCRR NIH HHS/United States ; P30 EY001583/EY/NEI NIH HHS/United States ; R01 EY017549/EY/NEI NIH HHS/United States ; R01 EY025752/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Bestrophins/*genetics ; Dog Diseases/therapy ; Dogs ; Eye Diseases, Hereditary/diagnostic imaging/pathology/*therapy/veterinary ; Female ; Genetic Therapy/*methods ; Genetic Vectors/pharmacology ; Humans ; Light ; Male ; Mutation ; Retinal Detachment/diagnostic imaging/pathology/therapy ; Retinal Diseases/diagnostic imaging/pathology/*therapy/veterinary ; Retinal Pigment Epithelium/pathology ; Tomography, Optical Coherence ; }, abstract = {Mutations in the BEST1 gene cause detachment of the retina and degeneration of photoreceptor (PR) cells due to a primary channelopathy in the neighboring retinal pigment epithelium (RPE) cells. The pathophysiology of the interaction between RPE and PR cells preceding the formation of retinal detachment remains not well-understood. Our studies of molecular pathology in the canine BEST1 disease model revealed retina-wide abnormalities at the RPE-PR interface associated with defects in the RPE microvillar ensheathment and a cone PR-associated insoluble interphotoreceptor matrix. In vivo imaging demonstrated a retina-wide RPE-PR microdetachment, which contracted with dark adaptation and expanded upon exposure to a moderate intensity of light. Subretinal BEST1 gene augmentation therapy using adeno-associated virus 2 reversed not only clinically detectable subretinal lesions but also the diffuse microdetachments. Immunohistochemical analyses showed correction of the structural alterations at the RPE-PR interface in areas with BEST1 transgene expression. Successful treatment effects were demonstrated in three different canine BEST1 genotypes with vector titers in the 0.1-to-5E11 vector genomes per mL range. Patients with biallelic BEST1 mutations exhibited large regions of retinal lamination defects, severe PR sensitivity loss, and slowing of the retinoid cycle. Human translation of canine BEST1 gene therapy success in reversal of macro- and microdetachments through restoration of cytoarchitecture at the RPE-PR interface has promise to result in improved visual function and prevent disease progression in patients affected with bestrophinopathies.}, } @article {pmid29507197, year = {2018}, author = {Chen, L and Azuma, T and Yu, W and Zheng, X and Luo, L and Chen, L}, title = {B7-H1 maintains the polyclonal T cell response by protecting dendritic cells from cytotoxic T lymphocyte destruction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3126-3131}, pmid = {29507197}, issn = {1091-6490}, support = {P30 CA016359/CA/NCI NIH HHS/United States ; P50 CA121974/CA/NCI NIH HHS/United States ; P50 CA196530/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; B7-1 Antigen/immunology/*metabolism ; Dendritic Cells/*physiology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Neoplasms, Experimental/immunology/metabolism ; T-Lymphocytes, Cytotoxic/*physiology ; }, abstract = {Induced B7-H1 expression in the tumor microenvironment initiates adaptive resistance, which impairs immune functions and leads to tumor escape from immune destruction. Antibody blockade of the B7-H1/PD-1 interaction overcomes adaptive resistance, leading to regression of advanced human cancers and survival benefits in a significant fraction of patients. In addition to cancer cells, B7-H1 is expressed on dendritic cells (DCs), but its role in DC functions is less understood. DCs can present multiple antigens (Ags) to stimulate dominant or subdominant T cell responses. Here, we show that immunization with multiple tumor Ag-loaded DCs, in the absence of B7-H1, vastly enhances cytotoxic T lymphocyte (CTL) responses to dominant Ag. In sharp contrast, CTL responses to subdominant Ag were paradoxically suppressed, facilitating outgrowth of tumor variants carrying only subdominant Ag. Suppressed CTL responses to subdominant Ag are largely due to the loss of B7-H1-mediated protection of DCs from the lysis of CTL against dominant Ag. Therefore, B7-H1 expression on DCs may help maintain the diversity of CTL responses to multiple tumor Ags. Interestingly, a split immunization approach, which presents dominant and subdominant Ags with different DCs, promoted CTL responses to all Ags and prevented tumor escape in murine tumor models. These findings have implications for the design of future combination cancer immunotherapies.}, } @article {pmid29507196, year = {2018}, author = {Clarkson, MO and Stirling, CH and Jenkyns, HC and Dickson, AJ and Porcelli, D and Moy, CM and Pogge von Strandmann, PAE and Cooke, IR and Lenton, TM}, title = {Uranium isotope evidence for two episodes of deoxygenation during Oceanic Anoxic Event 2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2918-2923}, pmid = {29507196}, issn = {1091-6490}, abstract = {Oceanic Anoxic Event 2 (OAE 2), occurring ∼94 million years ago, was one of the most extreme carbon cycle and climatic perturbations of the Phanerozoic Eon. It was typified by a rapid rise in atmospheric CO2, global warming, and marine anoxia, leading to the widespread devastation of marine ecosystems. However, the precise timing and extent to which oceanic anoxic conditions expanded during OAE 2 remains unresolved. We present a record of global ocean redox changes during OAE 2 using a combined geochemical and carbon cycle modeling approach. We utilize a continuous, high-resolution record of uranium isotopes in pelagic and platform carbonate sediments to quantify the global extent of seafloor anoxia during OAE 2. This dataset is then compared with a dynamic model of the coupled global carbon, phosphorus, and uranium cycles to test hypotheses for OAE 2 initiation. This unique approach highlights an intra-OAE complexity that has previously been underconstrained, characterized by two expansions of anoxia separated by an episode of globally significant reoxygenation coincident with the "Plenus Cold Event." Each anoxic expansion event was likely driven by rapid atmospheric CO2 injections from multiphase Large Igneous Province activity.}, } @article {pmid29507195, year = {2018}, author = {Tilot, AK and Kucera, KS and Vino, A and Asher, JE and Baron-Cohen, S and Fisher, SE}, title = {Rare variants in axonogenesis genes connect three families with sound-color synesthesia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3168-3173}, pmid = {29507195}, issn = {1091-6490}, mesh = {Auditory Perception/*genetics/physiology ; Axons/*physiology ; Collagen Type IV/genetics ; Color Perception/*genetics/physiology ; Female ; Gene Expression ; Genetic Variation ; Humans ; Integrin alpha2/genetics ; Intercellular Signaling Peptides and Proteins/genetics ; Male ; Myosins/genetics ; Nerve Tissue Proteins/genetics ; Pedigree ; Perceptual Disorders/etiology/*genetics ; RGS Proteins/genetics ; Receptors, Immunologic/genetics ; Sodium-Hydrogen Exchangers/genetics ; }, abstract = {Synesthesia is a rare nonpathological phenomenon where stimulation of one sense automatically provokes a secondary perception in another. Hypothesized to result from differences in cortical wiring during development, synesthetes show atypical structural and functional neural connectivity, but the underlying molecular mechanisms are unknown. The trait also appears to be more common among people with autism spectrum disorder and savant abilities. Previous linkage studies searching for shared loci of large effect size across multiple families have had limited success. To address the critical lack of candidate genes, we applied whole-exome sequencing to three families with sound-color (auditory-visual) synesthesia affecting multiple relatives across three or more generations. We identified rare genetic variants that fully cosegregate with synesthesia in each family, uncovering 37 genes of interest. Consistent with reports indicating genetic heterogeneity, no variants were shared across families. Gene ontology analyses highlighted six genes-COL4A1, ITGA2, MYO10, ROBO3, SLC9A6, and SLIT2-associated with axonogenesis and expressed during early childhood when synesthetic associations are formed. These results are consistent with neuroimaging-based hypotheses about the role of hyperconnectivity in the etiology of synesthesia and offer a potential entry point into the neurobiology that organizes our sensory experiences.}, } @article {pmid29507194, year = {2018}, author = {}, title = {Correction for Haines et al., New twist on artificial muscles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2663}, doi = {10.1073/pnas.1802492115}, pmid = {29507194}, issn = {1091-6490}, } @article {pmid29507193, year = {2018}, author = {McWilliam, M and Hoogenboom, MO and Baird, AH and Kuo, CY and Madin, JS and Hughes, TP}, title = {Biogeographical disparity in the functional diversity and redundancy of corals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3084-3089}, pmid = {29507193}, issn = {1091-6490}, mesh = {*Animal Distribution ; Animals ; Anthozoa/*classification/*physiology ; *Biodiversity ; Principal Component Analysis ; }, abstract = {Corals are major contributors to a range of key ecosystem functions on tropical reefs, including calcification, photosynthesis, nutrient cycling, and the provision of habitat structure. The abundance of corals is declining at multiple scales, and the species composition of assemblages is responding to escalating human pressures, including anthropogenic global warming. An urgent challenge is to understand the functional consequences of these shifts in abundance and composition in different biogeographical contexts. While global patterns of coral species richness are well known, the biogeography of coral functions in provinces and domains with high and low redundancy is poorly understood. Here, we quantify the functional traits of all currently recognized zooxanthellate coral species (n = 821) in both the Indo-Pacific and Atlantic domains to examine the relationships between species richness and the diversity and redundancy of functional trait space. We find that trait diversity is remarkably conserved (>75% of the global total) along latitudinal and longitudinal gradients in species richness, falling away only in species-poor provinces (n < 200), such as the Persian Gulf (52% of the global total), Hawaii (37%), the Caribbean (26%), and the East-Pacific (20%), where redundancy is also diminished. In the more species-poor provinces, large and ecologically important areas of trait space are empty, or occupied by just a few, highly distinctive species. These striking biogeographical differences in redundancy could affect the resilience of critical reef functions and highlight the vulnerability of relatively depauperate, peripheral locations, which are often a low priority for targeted conservation efforts.}, } @article {pmid29507192, year = {2018}, author = {Muller, CJ and Romps, DM}, title = {Acceleration of tropical cyclogenesis by self-aggregation feedbacks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2930-2935}, doi = {10.1073/pnas.1719967115}, pmid = {29507192}, issn = {1091-6490}, abstract = {Idealized simulations of tropical moist convection have revealed that clouds can spontaneously clump together in a process called self-aggregation. This results in a state where a moist cloudy region with intense deep convection is surrounded by extremely dry subsiding air devoid of deep convection. Because of the idealized settings of the simulations where it was discovered, the relevance of self-aggregation to the real world is still debated. Here, we show that self-aggregation feedbacks play a leading-order role in the spontaneous genesis of tropical cyclones in cloud-resolving simulations. Those feedbacks accelerate the cyclogenesis process by a factor of 2, and the feedbacks contributing to the cyclone formation show qualitative and quantitative agreement with the self-aggregation process. Once the cyclone is formed, wind-induced surface heat exchange (WISHE) effects dominate, although we find that self-aggregation feedbacks have a small but nonnegligible contribution to the maintenance of the mature cyclone. Our results suggest that self-aggregation, and the framework developed for its study, can help shed more light into the physical processes leading to cyclogenesis and cyclone intensification. In particular, our results point out the importance of the longwave radiative cooling outside the cyclone.}, } @article {pmid29507191, year = {2018}, author = {Tsui, C and Inouye, C and Levy, M and Lu, A and Florens, L and Washburn, MP and Tjian, R}, title = {dCas9-targeted locus-specific protein isolation method identifies histone gene regulators.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2734-E2741}, pmid = {29507191}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {3' Untranslated Regions ; Animals ; Bacterial Proteins/*genetics/metabolism ; CRISPR-Associated Protein 9 ; Chromatin/genetics/*isolation & purification ; Chromatin Immunoprecipitation ; Chromosomal Proteins, Non-Histone/*genetics/metabolism ; Drosophila Proteins/*genetics/metabolism ; Drosophila melanogaster/genetics ; Endonucleases/*genetics/metabolism ; Gene Expression ; Genes, Regulator/*genetics ; Histones/*genetics/metabolism ; Humans ; Promoter Regions, Genetic ; RNA, Guide/genetics/metabolism ; RNA-Binding Proteins/*genetics/metabolism ; Recombinant Proteins/genetics/metabolism ; }, abstract = {Eukaryotic gene regulation is a complex process, often coordinated by the action of tens to hundreds of proteins. Although previous biochemical studies have identified many components of the basal machinery and various ancillary factors involved in gene regulation, numerous gene-specific regulators remain undiscovered. To comprehensively survey the proteome directing gene expression at a specific genomic locus of interest, we developed an in vitro nuclease-deficient Cas9 (dCas9)-targeted chromatin-based purification strategy, called "CLASP" (Cas9 locus-associated proteome), to identify and functionally test associated gene-regulatory factors. Our CLASP method, coupled to mass spectrometry and functional screens, can be efficiently adapted for isolating associated regulatory factors in an unbiased manner targeting multiple genomic loci across different cell types. Here, we applied our method to isolate the Drosophila melanogaster histone cluster in S2 cells to identify several factors including Vig and Vig2, two proteins that bind and regulate core histone H2A and H3 mRNA via interaction with their 3' UTRs.}, } @article {pmid29507190, year = {2018}, author = {Mitchell, LE and Lin, JC and Bowling, DR and Pataki, DE and Strong, C and Schauer, AJ and Bares, R and Bush, SE and Stephens, BB and Mendoza, D and Mallia, D and Holland, L and Gurney, KR and Ehleringer, JR}, title = {Long-term urban carbon dioxide observations reveal spatial and temporal dynamics related to urban characteristics and growth.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2912-2917}, pmid = {29507190}, issn = {1091-6490}, abstract = {Cities are concentrated areas of CO2 emissions and have become the foci of policies for mitigation actions. However, atmospheric measurement networks suitable for evaluating urban emissions over time are scarce. Here we present a unique long-term (decadal) record of CO2 mole fractions from five sites across Utah's metropolitan Salt Lake Valley. We examine "excess" CO2 above background conditions resulting from local emissions and meteorological conditions. We ascribe CO2 trends to changes in emissions, since we did not find long-term trends in atmospheric mixing proxies. Three contrasting CO2 trends emerged across urban types: negative trends at a residential-industrial site, positive trends at a site surrounded by rapid suburban growth, and relatively constant CO2 over time at multiple sites in the established, residential, and commercial urban core. Analysis of population within the atmospheric footprints of the different sites reveals approximately equal increases in population influencing the observed CO2, implying a nonlinear relationship with CO2 emissions: Population growth in rural areas that experienced suburban development was associated with increasing emissions while population growth in the developed urban core was associated with stable emissions. Four state-of-the-art global-scale emission inventories also have a nonlinear relationship with population density across the city; however, in contrast to our observations, they all have nearly constant emissions over time. Our results indicate that decadal scale changes in urban CO2 emissions are detectable through monitoring networks and constitute a valuable approach to evaluate emission inventories and studies of urban carbon cycles.}, } @article {pmid29507189, year = {2018}, author = {Chu, DKW and Hui, KPY and Perera, RAPM and Miguel, E and Niemeyer, D and Zhao, J and Channappanavar, R and Dudas, G and Oladipo, JO and Traoré, A and Fassi-Fihri, O and Ali, A and Demissié, GF and Muth, D and Chan, MCW and Nicholls, JM and Meyerholz, DK and Kuranga, SA and Mamo, G and Zhou, Z and So, RTY and Hemida, MG and Webby, RJ and Roger, F and Rambaut, A and Poon, LLM and Perlman, S and Drosten, C and Chevalier, V and Peiris, M}, title = {MERS coronaviruses from camels in Africa exhibit region-dependent genetic diversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3144-3149}, pmid = {29507189}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; HHSN272201400006C/AI/NIAID NIH HHS/United States ; P01 AI060699/AI/NIAID NIH HHS/United States ; R01 AI129269/AI/NIAID NIH HHS/United States ; 206298//Wellcome Trust/United Kingdom ; }, mesh = {Africa ; Animals ; Camelus/*virology ; Coronavirus Infections/veterinary/virology ; Female ; *Genetic Variation ; Humans ; Lung/virology ; Mice, Inbred C57BL ; Middle East Respiratory Syndrome Coronavirus/*genetics/*pathogenicity ; Phylogeny ; Virus Replication ; Zoonoses/virology ; }, abstract = {Middle East respiratory syndrome coronavirus (MERS-CoV) causes a zoonotic respiratory disease of global public health concern, and dromedary camels are the only proven source of zoonotic infection. Although MERS-CoV infection is ubiquitous in dromedaries across Africa as well as in the Arabian Peninsula, zoonotic disease appears confined to the Arabian Peninsula. MERS-CoVs from Africa have hitherto been poorly studied. We genetically and phenotypically characterized MERS-CoV from dromedaries sampled in Morocco, Burkina Faso, Nigeria, and Ethiopia. Viruses from Africa (clade C) are phylogenetically distinct from contemporary viruses from the Arabian Peninsula (clades A and B) but remain antigenically similar in microneutralization tests. Viruses from West (Nigeria, Burkina Faso) and North (Morocco) Africa form a subclade, C1, that shares clade-defining genetic signatures including deletions in the accessory gene ORF4b Compared with human and camel MERS-CoV from Saudi Arabia, virus isolates from Burkina Faso (BF785) and Nigeria (Nig1657) had lower virus replication competence in Calu-3 cells and in ex vivo cultures of human bronchus and lung. BF785 replicated to lower titer in lungs of human DPP4-transduced mice. A reverse genetics-derived recombinant MERS-CoV (EMC) lacking ORF4b elicited higher type I and III IFN responses than the isogenic EMC virus in Calu-3 cells. However, ORF4b deletions may not be the major determinant of the reduced replication competence of BF785 and Nig1657. Genetic and phenotypic differences in West African viruses may be relevant to zoonotic potential. There is an urgent need for studies of MERS-CoV at the animal-human interface.}, } @article {pmid29507188, year = {2018}, author = {}, title = {Correction for D'Asaro et al., Ocean convergence and the dispersion of flotsam.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2664}, doi = {10.1073/pnas.1802701115}, pmid = {29507188}, issn = {1091-6490}, } @article {pmid29506573, year = {2018}, author = {Chalmers, K and Badgery-Parker, T and Pearson, SA and Brett, J and Scott, IA and Elshaug, AG}, title = {Developing indicators for measuring low-value care: mapping Choosing Wisely recommendations to hospital data.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {163}, pmid = {29506573}, issn = {1756-0500}, support = {1109626//National Health and Medical Research Council/ ; 1060407//National Health and Medical Research Council/ ; 1094304//National Health and Medical Research Council/ ; }, mesh = {Australia ; Canada ; Datasets as Topic ; Health Services Research/*statistics & numerical data ; Hospitals/*statistics & numerical data ; Humans ; *Quality Indicators, Health Care ; United Kingdom ; United States ; }, abstract = {OBJECTIVE: Low-value health care refers to interventions where the risk of harm or costs exceeds the likely benefit for a patient. We aimed to develop indicators of low-value care, based on selected Choosing Wisely (CW) recommendations, applicable to routinely collected, hospital claims data.

RESULTS: We assessed 824 recommendations from the United States, Canada, Australia and the United Kingdom CW lists regarding their capacity to be measured in administrative hospital admissions datasets. We selected recommendations if they met the following criteria: the service occurred in the hospital setting (observable in setting); a claim recorded the use of the service (record of service); the appropriate/inappropriate use of the service could be mapped to information within the hospital claim (indication); and the service is consistently recorded in the claims (consistent documentation). We identified 17 recommendations (15 services) as measurable. We then developed low-value care indicators for two hospital datasets based on the selected recommendations, previously published indicators, and clinical input.}, } @article {pmid29506565, year = {2018}, author = {Sauvage, T and Plouviez, S and Schmidt, WE and Fredericq, S}, title = {TREE2FASTA: a flexible Perl script for batch extraction of FASTA sequences from exploratory phylogenetic trees.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {164}, pmid = {29506565}, issn = {1756-0500}, support = {1455569//NSF DEB/ ; }, mesh = {*Biodiversity ; *Databases, Nucleic Acid ; *Phylogeny ; *Sequence Analysis, DNA ; *Software ; }, abstract = {OBJECTIVE: The body of DNA sequence data lacking taxonomically informative sequence headers is rapidly growing in user and public databases (e.g. sequences lacking identification and contaminants). In the context of systematics studies, sorting such sequence data for taxonomic curation and/or molecular diversity characterization (e.g. crypticism) often requires the building of exploratory phylogenetic trees with reference taxa. The subsequent step of segregating DNA sequences of interest based on observed topological relationships can represent a challenging task, especially for large datasets.

RESULTS: We have written TREE2FASTA, a Perl script that enables and expedites the sorting of FASTA-formatted sequence data from exploratory phylogenetic trees. TREE2FASTA takes advantage of the interactive, rapid point-and-click color selection and/or annotations of tree leaves in the popular Java tree-viewer FigTree to segregate groups of FASTA sequences of interest to separate files. TREE2FASTA allows for both simple and nested segregation designs to facilitate the simultaneous preparation of multiple data sets that may overlap in sequence content.}, } @article {pmid29506558, year = {2018}, author = {Habuka, M and Wada, Y and Kurosawa, Y and Yamamoto, S and Tani, Y and Ohashi, R and Ajioka, Y and Nakano, M and Narita, I}, title = {Fatal visceral disseminated varicella zoster infection during initial remission induction therapy in a patient with lupus nephritis and rheumatoid arthritis-possible association with mycophenolate mofetil and high-dose glucocorticoid therapy: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {165}, pmid = {29506558}, issn = {1756-0500}, mesh = {Arthritis, Rheumatoid/*drug therapy ; Enzyme Inhibitors/*adverse effects ; Fatal Outcome ; Female ; Herpes Zoster/*complications/*etiology ; Humans ; Lupus Nephritis/*drug therapy ; Middle Aged ; Mycophenolic Acid/*adverse effects ; }, abstract = {BACKGROUND: Visceral disseminated varicella zoster viral (VZV) infection is a rare but severe complication with a high mortality rate in immunosuppressed individuals, and an increased susceptibility to VZV has been reported in kidney transplant recipients who are treated with mycophenolate mofetil (MMF). In Japan, MMF is currently approved for patients with lupus nephritis (LN) and data to indicate its optimal dosage are still insufficient.

CASE PRESENTATION: A 46-year-old Japanese woman with rheumatoid arthritis was diagnosed as having systemic lupus erythematosus (SLE) and LN class III (A/C). Although initial remission-induction therapy with prednisolone and tacrolimus was started, her serum creatinine level and urinary protein excretion were elevated. Methylprednisolone pulse therapy was added, and tacrolimus was switched to MMF. Two months after admission when she was taking 40 mg of PSL and 1500 mg of MMF daily, she suddenly developed upper abdominal pain and multiple skin blisters, and disseminated visceral VZV infection was diagnosed. Laboratory examinations demonstrated rapid exacerbation of severe acute liver failure and coagulation abnormalities despite immediate multidisciplinary treatment, and she died of hemorrhagic shock 7 days after the onset of abdominal pain. A serum sample collected at the time of admission revealed that she had recursive VZV infection.

CONCLUSIONS: MMF together with high-dose glucocorticoid therapy may increase the risk of VZV infection in Asian patients with SLE. Accumulation of evidence for parameters of safety, such as the area under the blood concentration-time curve of mycophenolic acid, should be urgently considered in order to establish a safer protocol for remission induction therapy in Asian patients with LN.}, } @article {pmid29506533, year = {2018}, author = {Simion, P and Belkhir, K and François, C and Veyssier, J and Rink, JC and Manuel, M and Philippe, H and Telford, MJ}, title = {A software tool 'CroCo' detects pervasive cross-species contamination in next generation sequencing data.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {28}, pmid = {29506533}, issn = {1741-7007}, support = {322790//European Research Council/International ; BB/H006966/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Multiple RNA samples are frequently processed together and often mixed before multiplex sequencing in the same sequencing run. While different samples can be separated post sequencing using sample barcodes, the possibility of cross contamination between biological samples from different species that have been processed or sequenced in parallel has the potential to be extremely deleterious for downstream analyses.

RESULTS: We present CroCo, a software package for identifying and removing such cross contaminants from assembled transcriptomes. Using multiple, recently published sequence datasets, we show that cross contamination is consistently present at varying levels in real data. Using real and simulated data, we demonstrate that CroCo detects contaminants efficiently and correctly. Using a real example from a molecular phylogenetic dataset, we show that contaminants, if not eliminated, can have a decisive, deleterious impact on downstream comparative analyses.

CONCLUSIONS: Cross contamination is pervasive in new and published datasets and, if undetected, can have serious deleterious effects on downstream analyses. CroCo is a database-independent, multi-platform tool, designed for ease of use, that efficiently and accurately detects and removes cross contamination in assembled transcriptomes to avoid these problems. We suggest that the use of CroCo should become a standard cleaning step when processing multiple samples for transcriptome sequencing.}, } @article {pmid29506508, year = {2018}, author = {Jung, J and Kwon, M and Bae, S and Yim, S and Lee, D}, title = {Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {26}, pmid = {29506508}, issn = {1752-0509}, support = {2012M3A9C4048758//National Research Foundation of Korea/ ; 2012M3A9C4048758//National Research Foundation of Korea/ ; 2012M3A9C4048758//National Research Foundation of Korea/ ; 2012M3A9C4048758//National Research Foundation of Korea/ ; 2012M3A9C4048758//National Research Foundation of Korea/ ; }, abstract = {BACKGROUND: Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy.

RESULTS: The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value < 0.05). Furthermore, we noticed that they included several proteins that could not be characterized by the shortest path analysis. The three potential targets, i.e. BMPR1B, ROCK, and LEPR, were manually validated with the literature.

CONCLUSIONS: In this study, we suggest a new approach to predict potential therapeutic targets of muscle atrophy with an analysis of phosphorylation status simulated by Petri net. We generated a list of the potential therapeutic targets whose inhibition recovers abnormally phosphorylated proteins in an atrophic state. They were evaluated by various approaches, such as Western blotting, GO terms, literature, known muscle atrophy-related genes and shortest path analysis. We expect the new proposed strategy to provide an understanding of phosphorylation status in muscle atrophy and to provide assistance towards identifying new therapies.}, } @article {pmid29506485, year = {2018}, author = {Cogburn, LA and Smarsh, DN and Wang, X and Trakooljul, N and Carré, W and White, HB}, title = {Transcriptional profiling of liver in riboflavin-deficient chicken embryos explains impaired lipid utilization, energy depletion, massive hemorrhaging, and delayed feathering.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {177}, pmid = {29506485}, issn = {1471-2164}, support = {00-52100-9614//U.S. Department of Agriculture (USDA)-Initiative for Future Agriculture and Food Systems (IFAFS)/International ; 2005-35206-15288//USDA-National Research Initiative (NRI)/International ; }, mesh = {Animals ; Chick Embryo ; *Chickens ; Energy Metabolism ; Feathers/*growth & development/metabolism ; Hemorrhage/genetics/pathology/veterinary ; Lipids/genetics ; Liver/metabolism/*pathology ; Poultry Diseases/*genetics/metabolism/pathology ; Riboflavin/metabolism ; Riboflavin Deficiency/*genetics/metabolism/pathology/*veterinary ; }, abstract = {BACKGROUND: A strain of Leghorn chickens (rd/rd), unable to produce a functional riboflavin-binding protein, lays riboflavin-deficient eggs, in which all embryos suddenly die at mid-incubation (days 13-15). This malady, caused by riboflavin deficiency, leads to excessive lipid accumulation in liver, impaired β-oxidation of lipid, and severe hypoglycemia prior to death. We have used high-density chicken microarrays for time-course transcriptional scans of liver in chicken embryos between days 9-15 during this riboflavin-deficiency-induced metabolic catastrophe. For comparison, half of rd/rd embryos (n = 16) were rescued from this calamity by injection of riboflavin just prior to incubation of fertile eggs from rd/rd hens.

RESULTS: No significant differences were found between hepatic transcriptomes of riboflavin-deficient and riboflavin-rescued embryos at the first two ages (days 9 and 11). Overall, we found a 3.2-fold increase in the number of differentially expressed hepatic genes between day 13 (231 genes) and day 15 (734 genes). Higher expression of genes encoding the chicken flavoproteome was more evident in rescued- (15 genes) than in deficient-embryos (4 genes) at day 15. Diminished activity of flavin-dependent enzymes in riboflavin-deficient embryos blocks catabolism of yolk lipids, which normally serves as the predominant source of energy required for embryonic development.

CONCLUSIONS: Riboflavin deficiency in mid-stage embryos leads to reduced expression of numerous genes controlling critical functions, including β-oxidation of lipids, blood coagulation and feathering. Surprisingly, reduced expression of feather keratin 1 was found in liver of riboflavin-deficient embryos at e15, which could be related to their delayed feathering and sparse clubbed down. A large number of genes are expressed at higher levels in liver of riboflavin-deficient embryos; these up-regulated genes control lipid storage/transport, gluconeogenesis, ketogenesis, protein catabolism/ubiquitination and cell death.}, } @article {pmid29506476, year = {2018}, author = {Ip, JCH and Mu, H and Chen, Q and Sun, J and Ituarte, S and Heras, H and Van Bocxlaer, B and Ganmanee, M and Huang, X and Qiu, JW}, title = {AmpuBase: a transcriptome database for eight species of apple snails (Gastropoda: Ampullariidae).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {179}, pmid = {29506476}, issn = {1471-2164}, support = {JCYJ20170307161326613//Shenzhen Science and Technology Innovation Committee/International ; HKBU 12301415//General Research Fund of Hong Kong/International ; 0850 and 0122//Agencia Nacional de Promoción Científica y Tecnológica/International ; }, mesh = {Animals ; *Databases, Genetic ; Gene Expression Profiling ; Gene Ontology ; Genomics/methods ; High-Throughput Nucleotide Sequencing/methods ; Molecular Sequence Annotation ; Snails/*classification/*genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Gastropoda, with approximately 80,000 living species, is the largest class of Mollusca. Among gastropods, apple snails (family Ampullariidae) are globally distributed in tropical and subtropical freshwater ecosystems and many species are ecologically and economically important. Ampullariids exhibit various morphological and physiological adaptations to their respective habitats, which make them ideal candidates for studying adaptation, population divergence, speciation, and larger-scale patterns of diversity, including the biogeography of native and invasive populations. The limited availability of genomic data, however, hinders in-depth ecological and evolutionary studies of these non-model organisms.

RESULTS: Using Illumina Hiseq platforms, we sequenced 1220 million reads for seven species of apple snails. Together with the previously published RNA-Seq data of two apple snails, we conducted de novo transcriptome assembly of eight species that belong to five genera of Ampullariidae, two of which represent Old World lineages and the other three New World lineages. There were 20,730 to 35,828 unigenes with predicted open reading frames for the eight species, with N50 (shortest sequence length at 50% of the unigenes) ranging from 1320 to 1803 bp. 69.7% to 80.2% of these unigenes were functionally annotated by searching against NCBI's non-redundant, Gene Ontology database and the Kyoto Encyclopaedia of Genes and Genomes. With these data we developed AmpuBase, a relational database that features online BLAST functionality for DNA/protein sequences, keyword searching for unigenes/functional terms, and download functions for sequences and whole transcriptomes.

CONCLUSIONS: In summary, we have generated comprehensive transcriptome data for multiple ampullariid genera and species, and created a publicly accessible database with a user-friendly interface to facilitate future basic and applied studies on ampullariids, and comparative molecular studies with other invertebrates.}, } @article {pmid29506475, year = {2018}, author = {Siddiqui, JK and Baskin, E and Liu, M and Cantemir-Stone, CZ and Zhang, B and Bonneville, R and McElroy, JP and Coombes, KR and Mathé, EA}, title = {IntLIM: integration using linear models of metabolomics and gene expression data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {81}, pmid = {29506475}, issn = {1471-2105}, support = {P30 CA016058/CA/NCI NIH HHS/United States ; T15 LM011270/LM/NLM NIH HHS/United States ; T32 GM068412/GM/NIGMS NIH HHS/United States ; }, mesh = {Breast Neoplasms/genetics ; Cell Line, Tumor ; Databases, Genetic ; Female ; *Gene Expression Regulation ; Humans ; Linear Models ; Metabolome/genetics ; *Metabolomics ; Phenotype ; *Software ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Integration of transcriptomic and metabolomic data improves functional interpretation of disease-related metabolomic phenotypes, and facilitates discovery of putative metabolite biomarkers and gene targets. For this reason, these data are increasingly collected in large (> 100 participants) cohorts, thereby driving a need for the development of user-friendly and open-source methods/tools for their integration. Of note, clinical/translational studies typically provide snapshot (e.g. one time point) gene and metabolite profiles and, oftentimes, most metabolites measured are not identified. Thus, in these types of studies, pathway/network approaches that take into account the complexity of transcript-metabolite relationships may neither be applicable nor readily uncover novel relationships. With this in mind, we propose a simple linear modeling approach to capture disease-(or other phenotype) specific gene-metabolite associations, with the assumption that co-regulation patterns reflect functionally related genes and metabolites.

RESULTS: The proposed linear model, metabolite ~ gene + phenotype + gene:phenotype, specifically evaluates whether gene-metabolite relationships differ by phenotype, by testing whether the relationship in one phenotype is significantly different from the relationship in another phenotype (via a statistical interaction gene:phenotype p-value). Statistical interaction p-values for all possible gene-metabolite pairs are computed and significant pairs are then clustered by the directionality of associations (e.g. strong positive association in one phenotype, strong negative association in another phenotype). We implemented our approach as an R package, IntLIM, which includes a user-friendly R Shiny web interface, thereby making the integrative analyses accessible to non-computational experts. We applied IntLIM to two previously published datasets, collected in the NCI-60 cancer cell lines and in human breast tumor and non-tumor tissue, for which transcriptomic and metabolomic data are available. We demonstrate that IntLIM captures relevant tumor-specific gene-metabolite associations involved in known cancer-related pathways, including glutamine metabolism. Using IntLIM, we also uncover biologically relevant novel relationships that could be further tested experimentally.

CONCLUSIONS: IntLIM provides a user-friendly, reproducible framework to integrate transcriptomic and metabolomic data and help interpret metabolomic data and uncover novel gene-metabolite relationships. The IntLIM R package is publicly available in GitHub (https://github.com/mathelab/IntLIM) and includes a user-friendly web application, vignettes, sample data and data/code to reproduce results.}, } @article {pmid29506474, year = {2018}, author = {Tsai, TC and Shih, CC and Chien, HP and Yang, AH and Lu, JK and Lu, JH}, title = {Anti-apoptotic effects of IGF-I on mortality and dysmorphogenesis in tbx5-deficient zebrafish embryos.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {5}, pmid = {29506474}, issn = {1471-213X}, abstract = {BACKGROUND: Tbx5 deficiency in zebrafish causes several abnormal phenotypes of the heart and pectoral fins. It has been reported that exogenous human growth hormone can enhance expression of downstream mediators in the growth hormone and insulin-like growth factor I (IGF-I) pathway and partially restore dysmorphogenesis in tbx5 morphants. This study aimed to further evaluate the effects of IGF-I on cell apoptosis and dysmorphogenesis in zebrafish embryos deficient for tbx5.

RESULTS: Among the five studied groups of zebrafish embryos (wild-type embryos [WT], tbx5 morphants [MO], mismatched tbx5 morpholino-treated wild-type embryos [MIS], IGF-I-treated wild-type embryos [WTIGF1], and IGF-I-treated tbx5 morphants [MOIGF1]), the expression levels of the ifg1, igf1-ra, ifg-rb, erk1, and akt2 genes as well as the ERK and AKT proteins were significantly reduced in the MO group, but were partially restored in the MOIGF1 group. These expression levels remained normal in the WT, MIS, and WTIGF1 groups. Exogenous human IGF-I also reduced the incidence of phenotypic anomalies, decreased the expression levels of apoptotic genes and proteins, suppressed cell apoptosis, and improved survival of the MOIGF1 group.

CONCLUSIONS: These results suggest that IGF-I has an anti-apoptotic protective effect in zebrafish embryos with tbx5 deficiency.}, } @article {pmid29506473, year = {2018}, author = {Chai, G and Li, C and Xu, F and Li, Y and Shi, X and Wang, Y and Wang, Z}, title = {Three endoplasmic reticulum-associated fatty acyl-coenzyme a reductases were involved in the production of primary alcohols in hexaploid wheat (Triticum aestivum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {41}, pmid = {29506473}, issn = {1471-2229}, support = {31471568//National Natural Science Foundation of China/ ; 31271794//National Natural Science Foundation of China/ ; 2014KCT-25//Science and Technology Innovation Team Plan from shaanxi province, China/ ; }, mesh = {Abscisic Acid/pharmacology ; Acetates/pharmacology ; Aldehyde Oxidoreductases/genetics/*metabolism ; Cyclopentanes/pharmacology ; Endoplasmic Reticulum/drug effects/*enzymology ; Gene Expression Regulation, Plant/drug effects/genetics ; Oxylipins/pharmacology ; Plant Proteins/genetics/*metabolism ; *Polyploidy ; Triticum/drug effects/*enzymology/genetics ; Waxes/*metabolism ; }, abstract = {BACKGROUND: The cuticle covers the surface of the polysaccharide cell wall of leaf epidermal cells and forms an essential diffusion barrier between the plant and the environment. The cuticle is composed of cutin and wax. Cuticular wax plays an important role in the survival of plants by serving as the interface between plants and their biotic and abiotic environments, especially restricting nonstomatal water loss. Leaf cuticular waxes of hexaploid wheat at the seedling stage mainly consist of primary alcohols, aldehydes, fatty acids, alkane and esters. Primary alcohols account for more than 80% of the total wax load. Therefore, we cloned several genes encoding fatty acyl-coenzyme A reductases from wheat and analyzed their function in yeast and plants. We propose the potential use of these genes in wheat genetic breeding.

RESULTS: We reported the cloning and characterization of three TaFARs, namely TaFAR6, TaFAR7 and TaFAR8, encoding fatty acyl-coenzyme A reductases (FAR) in wheat leaf cuticle. Expression analysis revealed that TaFAR6, TaFAR7 and TaFAR8 were expressed at the higher levels in the seedling leaf blades, and were expressed moderately or weakly in stamen, glumes, peduncle, flag leaf blade, sheath, spike, and pistil. The heterologous expression of three TaFARs in yeast (Saccharomyces cerevisiae) led to the production of C24:0 and C26:0 primary alcohols. Transgenic expression of the three TaFARs in tomato (Solanum lycopersicum) and rice (Oryza sativa) led to increased accumulation of C24:0-C30:0 primary alcohols. Transient expression of GFP protein-tagged TaFARs revealed that the three TaFAR proteins were localized to the endoplasmic reticulum (ER), the site of wax biosynthesis. The three TaFAR genes were transcriptionally induced by drought, cold, heat, powdery mildew (Blumeria graminis) infection, abscisic acid (ABA) and methyl jasmonate (MeJa) treatments.

CONCLUSIONS: These results indicated that wheat TaFAR6, TaFAR7 and TaFAR8 are involved in biosynthesis of very-long-chain primary alcohols in hexaploid wheat and in response to multiple environmental stresses.}, } @article {pmid29506470, year = {2018}, author = {Abnousi, A and Broschat, SL and Kalyanaraman, A}, title = {Alignment-free clustering of large data sets of unannotated protein conserved regions using minhashing.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {83}, pmid = {29506470}, issn = {1471-2105}, support = {1262664//National Science Foundation/International ; }, mesh = {*Algorithms ; Amino Acid Sequence ; Cluster Analysis ; *Databases, Protein ; *Molecular Sequence Annotation ; Phylogeny ; Protein Domains ; Rickettsia/classification ; Sequence Alignment/*methods ; }, abstract = {BACKGROUND: Clustering of protein sequences is of key importance in predicting the structure and function of newly sequenced proteins and is also of use for their annotation. With the advent of multiple high-throughput sequencing technologies, new protein sequences are becoming available at an extraordinary rate. The rapid growth rate has impeded deployment of existing protein clustering/annotation tools which depend largely on pairwise sequence alignment.

RESULTS: In this paper, we propose an alignment-free clustering approach, coreClust, for annotating protein sequences using detected conserved regions. The proposed algorithm uses Min-Wise Independent Hashing for identifying similar conserved regions. Min-Wise Independent Hashing works by generating a (w,c)-sketch for each document and comparing these sketches. Our algorithm fits well within the MapReduce framework, permitting scalability. We show that coreClust generates results comparable to existing known methods. In particular, we show that the clusters generated by our algorithm capture the subfamilies of the Pfam domain families for which the sequences in a cluster have a similar domain architecture. We show that for a data set of 90,000 sequences (about 250,000 domain regions), the clusters generated by our algorithm give a 75% average weighted F1 score, our accuracy metric, when compared to the clusters generated by a semi-exhaustive pairwise alignment algorithm.

CONCLUSIONS: The new clustering algorithm can be used to generate meaningful clusters of conserved regions. It is a scalable method that when paired with our prior work, NADDA for detecting conserved regions, provides a complete end-to-end pipeline for annotating protein sequences.}, } @article {pmid29506469, year = {2018}, author = {Goyal, RK and Tulpan, D and Chomistek, N and González-Peña Fundora, D and West, C and Ellis, BE and Frick, M and Laroche, A and Foroud, NA}, title = {Analysis of MAPK and MAPKK gene families in wheat and related Triticeae species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {178}, pmid = {29506469}, issn = {1471-2164}, support = {N/A//Agriculture and Agri-Food Canada (CA), AgriFlexibility Grant/International ; N/A//Agriculture and Agri-Food Canada (CA), Genomics Research and Development Initiative/International ; }, mesh = {Amino Acid Sequence ; Computational Biology ; Databases, Factual ; *Gene Expression Regulation, Plant ; Genome, Plant ; Hordeum/*genetics/metabolism ; Lolium/*genetics/metabolism ; Mitogen-Activated Protein Kinase Kinases/genetics/*metabolism ; Mitogen-Activated Protein Kinases/genetics/*metabolism ; Multigene Family ; Phylogeny ; Sequence Alignment ; Triticum/*genetics/metabolism ; }, abstract = {BACKGROUND: The mitogen-activated protein kinase (MAPK) family is involved in signal transduction networks that underpin many different biological processes in plants, ranging from development to biotic and abiotic stress responses. To date this class of enzymes has received little attention in Triticeae species, which include important cereal crops (wheat, barley, rye and triticale) that represent over 20% of the total protein food-source worldwide.

RESULTS: The work presented here focuses on two subfamilies of Triticeae MAPKs, the MAP kinases (MPKs), and the MAPK kinases (MKKs) whose members phosphorylate the MPKs. In silico analysis of multiple Triticeae sequence databases led to the identification of 152 MAPKs belonging to these two sub-families. Some previously identified MAPKs were renamed to reflect the literature consensus on MAPK nomenclature. Two novel MPKs, MPK24 and MPK25, have been identified, including the first example of a plant MPK carrying the TGY activation loop sequence common to mammalian p38 MPKs. An EF-hand calcium-binding domain was found in members of the Triticeae MPK17 clade, a feature that appears to be specific to Triticeae species. New insights into the novel MEY activation loop identified in MPK11s are offered. When the exon-intron patterns for some MPKs and MKKs of wheat, barley and ancestors of wheat were assembled based on transcript data in GenBank, they showed deviations from the same sequence predicted in Ensembl. The functional relevance of MAPKs as derived from patterns of gene expression, MPK activation and MKK-MPK interaction is discussed.

CONCLUSIONS: A comprehensive resource of accurately annotated and curated Triticeae MPK and MKK sequences has been created for wheat, barley, rye, triticale, and two ancestral wheat species, goat grass and red wild einkorn. The work we present here offers a central information resource that will resolve existing confusion in the literature and sustain expansion of MAPK research in the crucial Triticeae grains.}, } @article {pmid29506467, year = {2018}, author = {Marvel, SW and To, K and Grimm, FA and Wright, FA and Rusyn, I and Reif, DM}, title = {ToxPi Graphical User Interface 2.0: Dynamic exploration, visualization, and sharing of integrated data models.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {80}, pmid = {29506467}, issn = {1471-2105}, support = {P30 ES025128/ES/NIEHS NIH HHS/United States ; Syngenta Fellowship Award//Society of Toxicology/International ; ES007329/ES/NIEHS NIH HHS/United States ; RD83516608//U.S. Environmental Protection Agency/International ; RD83580201//U.S. Environmental Protection Agency/International ; T32 ES007329/ES/NIEHS NIH HHS/United States ; P42 ES027704/ES/NIEHS NIH HHS/United States ; ES025128/ES/NIEHS NIH HHS/United States ; ES027704/ES/NIEHS NIH HHS/United States ; }, mesh = {Cluster Analysis ; *Information Dissemination ; Information Storage and Retrieval ; *Models, Theoretical ; *Software ; *User-Computer Interface ; }, abstract = {BACKGROUND: Drawing integrated conclusions from diverse source data requires synthesis across multiple types of information. The ToxPi (Toxicological Prioritization Index) is an analytical framework that was developed to enable integration of multiple sources of evidence by transforming data into integrated, visual profiles. Methodological improvements have advanced ToxPi and expanded its applicability, necessitating a new, consolidated software platform to provide functionality, while preserving flexibility for future updates.

RESULTS: We detail the implementation of a new graphical user interface for ToxPi (Toxicological Prioritization Index) that provides interactive visualization, analysis, reporting, and portability. The interface is deployed as a stand-alone, platform-independent Java application, with a modular design to accommodate inclusion of future analytics. The new ToxPi interface introduces several features, from flexible data import formats (including legacy formats that permit backward compatibility) to similarity-based clustering to options for high-resolution graphical output.

CONCLUSIONS: We present the new ToxPi interface for dynamic exploration, visualization, and sharing of integrated data models. The ToxPi interface is freely-available as a single compressed download that includes the main Java executable, all libraries, example data files, and a complete user manual from http://toxpi.org .}, } @article {pmid29506466, year = {2018}, author = {Lin, L and McKerrow, WH and Richards, B and Phonsom, C and Lawrence, CE}, title = {Characterization and visualization of RNA secondary structure Boltzmann ensemble via information theory.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {82}, pmid = {29506466}, issn = {1471-2105}, mesh = {*Algorithms ; Base Pairing/genetics ; Base Sequence ; Cluster Analysis ; Entropy ; *Information Theory ; Mutation/genetics ; *Nucleic Acid Conformation ; RNA/*chemistry ; }, abstract = {BACKGROUND: The nearest neighbor model and associated dynamic programming algorithms allow for the efficient estimation of the RNA secondary structure Boltzmann ensemble. However because a given RNA secondary structure only contains a fraction of the possible helices that could form from a given sequence, the Boltzmann ensemble is multimodal. Several methods exist for clustering structures and finding those modes. However less focus is given to exploring the underlying reasons for this multimodality: the presence of conflicting basepairs. Information theory, or more specifically mutual information, provides a method to identify those basepairs that are key to the secondary structure.

RESULTS: To this end we find most informative basepairs and visualize the effect of these basepairs on the secondary structure. Knowing whether a most informative basepair is present tells us not only the status of the particular pair but also provides a large amount of information about which other pairs are present or not present. We find that a few basepairs account for a large amount of the structural uncertainty. The identification of these pairs indicates small changes to sequence or stability that will have a large effect on structure.

CONCLUSION: We provide a novel algorithm that uses mutual information to identify the key basepairs that lead to a multimodal Boltzmann distribution. We then visualize the effect of these pairs on the overall Boltzmann ensemble.}, } @article {pmid29506465, year = {2018}, author = {Badal, VD and Kundrotas, PJ and Vakser, IA}, title = {Natural language processing in text mining for structural modeling of protein complexes.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {84}, pmid = {29506465}, issn = {1471-2105}, support = {R01 GM074255/GM/NIGMS NIH HHS/United States ; R01GM074255/NH/NIH HHS/United States ; DBI1262621//National Science Foundation/International ; DBI1565107//National Science Foundation/International ; }, mesh = {*Data Mining ; Machine Learning ; *Models, Molecular ; *Natural Language Processing ; Protein Binding ; Proteins/*chemistry ; Semantics ; Support Vector Machine ; }, abstract = {BACKGROUND: Structural modeling of protein-protein interactions produces a large number of putative configurations of the protein complexes. Identification of the near-native models among them is a serious challenge. Publicly available results of biomedical research may provide constraints on the binding mode, which can be essential for the docking. Our text-mining (TM) tool, which extracts binding site residues from the PubMed abstracts, was successfully applied to protein docking (Badal et al., PLoS Comput Biol, 2015; 11: e1004630). Still, many extracted residues were not relevant to the docking.

RESULTS: We present an extension of the TM tool, which utilizes natural language processing (NLP) for analyzing the context of the residue occurrence. The procedure was tested using generic and specialized dictionaries. The results showed that the keyword dictionaries designed for identification of protein interactions are not adequate for the TM prediction of the binding mode. However, our dictionary designed to distinguish keywords relevant to the protein binding sites led to considerable improvement in the TM performance. We investigated the utility of several methods of context analysis, based on dissection of the sentence parse trees. The machine learning-based NLP filtered the pool of the mined residues significantly more efficiently than the rule-based NLP. Constraints generated by NLP were tested in docking of unbound proteins from the DOCKGROUND X-ray benchmark set 4. The output of the global low-resolution docking scan was post-processed, separately, by constraints from the basic TM, constraints re-ranked by NLP, and the reference constraints. The quality of a match was assessed by the interface root-mean-square deviation. The results showed significant improvement of the docking output when using the constraints generated by the advanced TM with NLP.

CONCLUSIONS: The basic TM procedure for extracting protein-protein binding site residues from the PubMed abstracts was significantly advanced by the deep parsing (NLP techniques for contextual analysis) in purging of the initial pool of the extracted residues. Benchmarking showed a substantial increase of the docking success rate based on the constraints generated by the advanced TM with NLP.}, } @article {pmid29506259, year = {2018}, author = {Chrismas, NAM and Anesio, AM and Sánchez-Baracaldo, P}, title = {The future of genomics in polar and alpine cyanobacteria.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, pmid = {29506259}, issn = {1574-6941}, abstract = {In recent years, genomic analyses have arisen as an exciting way of investigating the functional capacity and environmental adaptations of numerous micro-organisms of global relevance, including cyanobacteria. In the extreme cold of Arctic, Antarctic and alpine environments, cyanobacteria are of fundamental ecological importance as primary producers and ecosystem engineers. While their role in biogeochemical cycles is well appreciated, little is known about the genomic makeup of polar and alpine cyanobacteria. In this article, we present ways that genomic techniques might be used to further our understanding of cyanobacteria in cold environments in terms of their evolution and ecology. Existing examples from other environments (e.g. marine/hot springs) are used to discuss how methods developed there might be used to investigate specific questions in the cryosphere. Phylogenomics, comparative genomics and population genomics are identified as methods for understanding the evolution and biogeography of polar and alpine cyanobacteria. Transcriptomics will allow us to investigate gene expression under extreme environmental conditions, and metagenomics can be used to complement tradition amplicon-based methods of community profiling. Finally, new techniques such as single cell genomics and metagenome assembled genomes will also help to expand our understanding of polar and alpine cyanobacteria that cannot readily be cultured.}, } @article {pmid29505826, year = {2018}, author = {Carneiro, J and Sampaio, I and de Sousa E Silva-Júnior, J and Farias, I and Hrbek, T and Pissinatti, A and Silva, R and Martins-Junior, A and Boubli, J and Ferrari, SF and Schneider, H}, title = {Phylogeny, molecular dating and zoogeographic history of the titi monkeys (Callicebus, Pitheciidae) of eastern Brazil.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {10-15}, doi = {10.1016/j.ympev.2018.03.001}, pmid = {29505826}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Brazil ; Humans ; Likelihood Functions ; *Phylogeny ; *Phylogeography ; Pitheciidae/*classification ; Species Specificity ; Time Factors ; }, abstract = {The titi monkeys belong to a genus of New World primates endemic to South America, which were recently reclassified in three genera (Cheracebus, Plecturocebus and Callicebus). The genus Callicebus, which currently includes five species, is endemic to eastern Brazil, occurring in the Caatinga, Savanna, and Atlantic Forest biomes. In the present study, we investigated the validity of these species and inferred their phylogenetic relationships, divergence times, and biogeographic patterns based on the molecular analysis of a concatenated sequence of 11 mitochondrial and nuclear DNA markers, derived from 13 specimens. We ran Maximum Likelihood (ML) and Bayesian Inference (BI) analyses, and estimated genetic distances, divergence times. Ancestral areas were estimated on BioGeoBears. Our results suggest that at about twelve million years ago, the ancestor of all titi monkeys inhabited a wide area that extended from the Amazon forest to the South of the Atlantic forest. A first vicariant event originated Cheracebus in the West of the Amazon and the ancestor of Callicebus and Plectorocebus which, later were separated by a second one. The diversification of Callicebus occurred during the Plio-Pleistocene (beginning at 5 Ma) probably influenced by climatic fluctuations and geological events. Therefore, the results of the present work confirmed the existence of five species that currently inhabit forested areas under increasing threat from human activities. Thus, a reliable diagnosis of the taxonomic status of species living in endangered environments is extremely important for the development of conservation measures.}, } @article {pmid29505739, year = {2018}, author = {Hong, L and Dumond, M and Zhu, M and Tsugawa, S and Li, CB and Boudaoud, A and Hamant, O and Roeder, AHK}, title = {Heterogeneity and Robustness in Plant Morphogenesis: From Cells to Organs.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {469-495}, doi = {10.1146/annurev-arplant-042817-040517}, pmid = {29505739}, issn = {1545-2123}, abstract = {Development is remarkably reproducible, producing organs with the same size, shape, and function repeatedly from individual to individual. For example, every flower on the Antirrhinum stalk has the same snapping dragon mouth. This reproducibility has allowed taxonomists to classify plants and animals according to their morphology. Yet these reproducible organs are composed of highly variable cells. For example, neighboring cells grow at different rates in Arabidopsis leaves, sepals, and shoot apical meristems. This cellular variability occurs in normal, wild-type organisms, indicating that cellular heterogeneity (or diversity in a characteristic such as growth rate) is either actively maintained or, at a minimum, not entirely suppressed. In fact, cellular heterogeneity can contribute to producing invariant organs. Here, we focus on how plant organs are reproducibly created during development from these highly variable cells.}, } @article {pmid29505738, year = {2018}, author = {Thiel, V and Tank, M and Bryant, DA}, title = {Diversity of Chlorophototrophic Bacteria Revealed in the Omics Era.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {21-49}, doi = {10.1146/annurev-arplant-042817-040500}, pmid = {29505738}, issn = {1545-2123}, abstract = {Because of recent advances in omics methodologies, knowledge of chlorophototrophy (i.e., chlorophyll-based phototrophy) in bacteria has rapidly increased. Chlorophototrophs currently are known to occur in seven bacterial phyla: Cyanobacteria, Proteobacteria, Chlorobi, Chloroflexi, Firmicutes, Acidobacteria, and Gemmatimonadetes. Other organisms that can produce chlorophylls and photochemical reaction centers may still be undiscovered. Here we summarize the current status of the taxonomy and phylogeny of chlorophototrophic bacteria as revealed by genomic methods. In specific cases, we briefly describe important ecophysiological and metabolic insights that have been gained from the application of genomic methods to these bacteria. In the 20 years since the completion of the Synechocystis sp. PCC 6803 genome in 1996, approximately 1,100 genomes have been sequenced, which represents nearly the complete diversity of known chlorophototrophic bacteria. These data are leading to new insights into many important processes, including photosynthesis, nitrogen and carbon fixation, cellular differentiation and development, symbiosis, and ecosystem functionality.}, } @article {pmid29505737, year = {2018}, author = {Fishman, L and Sweigart, AL}, title = {When Two Rights Make a Wrong: The Evolutionary Genetics of Plant Hybrid Incompatibilities.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {707-731}, doi = {10.1146/annurev-arplant-042817-040113}, pmid = {29505737}, issn = {1545-2123}, abstract = {Hybrids between flowering plant species often exhibit reduced fitness, including sterility and inviability. Such hybrid incompatibilities create barriers to genetic exchange that can promote reproductive isolation between diverging populations and, ultimately, speciation. Additionally, hybrid breakdown opens a window into hidden molecular and evolutionary processes occurring within species. Here, we review recent work on the mechanisms and origins of hybrid incompatibility in flowering plants, including both diverse genic interactions and chromosomal incompatibilities. Conflict and coevolution among and within plant genomes contributes to the evolution of some well-characterized genic incompatibilities, but duplication and drift also play important roles. Inversions, while contributing to speciation by suppressing recombination, rarely cause underdominant sterility. Translocations cause severe F1 sterility by disrupting meiosis in heterozygotes, making their fixation in outcrossing sister species a paradox. Evolutionary genomic analyses of both genic and chromosomal incompatibilities, in the context of population genetic theory, can explicitly test alternative scenarios for their origins.}, } @article {pmid29505176, year = {2018}, author = {Start, D}, title = {Animal behaviour and algal camouflage jointly structure predation and selection.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {773-778}, doi = {10.1111/jeb.13261}, pmid = {29505176}, issn = {1420-9101}, abstract = {Trait variation can structure interactions between individuals, thus shaping selection. Although antipredator strategies are an important component of many aquatic systems, how multiple antipredator traits interact to influence consumption and selection remains contentious. Here, I use a common larval dragonfly (Epitheca canis) and its predator (Anax junius) to test for the joint effects of activity rate and algal camouflage on predation and survival selection. I found that active and poorly camouflaged Epitheca were more likely to be consumed, and thus, survival selection favoured inactive and well-camouflaged individuals. Notably, camouflage dampened selection on activity rate, likely by reducing attack rates when Epitheca encountered a predator. Correlational selection is therefore conferred by the ecological interaction of traits, rather than by opposing selection acting on linked traits. I suggest that antipredator traits with different adaptive functions can jointly structure patterns of consumption and selection.}, } @article {pmid29505068, year = {2018}, author = {Antonelli, A and Favuzza, E and Galano, A and Montalbano Di Filippo, M and Ciccone, N and Berrilli, F and Mencucci, R and Di Cave, D and Rossolini, GM}, title = {Regional spread of contact lens-related Acanthamoeba keratitis in Italy.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {83-85}, pmid = {29505068}, issn = {1121-7138}, mesh = {Acanthamoeba/genetics/*isolation & purification ; Acanthamoeba Keratitis/*epidemiology ; Adult ; Aged ; *Contact Lenses/parasitology ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Phylogeny ; Real-Time Polymerase Chain Reaction/methods ; Young Adult ; }, abstract = {Acanthamoeba ocular infections, known as Acanthamoeba keratitis, are an emerging problem among contact lens wearers. Infections mediated by Acanthamoeba are uncommon, but they can be underestimated due to poor awareness and delayed diagnosis. The routine use of rapid and cost-effective molecular methods like Real Time PCR for the diagnosis of this important pathogen could improve diagnosis and therapy outcome. This report describes the detection by Real Time PCR assay of six T4 and one T3 Acanthamoeba infections, as the first reported cases in Tuscany, Italy.}, } @article {pmid29505067, year = {2018}, author = {Medici, MC and Tummolo, F and Martella, V and De Conto, F and Arcangeletti, MC and Pinardi, F and Ferraglia, F and Chezzi, C and Calderaro, A}, title = {Emergence of novel recombinant GII.P16_GII.2 and GII. P16_GII.4 Sydney 2012 norovirus strains in Italy, winter 2016/2017.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {71-72}, pmid = {29505067}, issn = {1121-7138}, mesh = {Adolescent ; Caliciviridae Infections/epidemiology/*virology ; Child ; Child, Preschool ; Genotype ; Humans ; Infant ; Italy/epidemiology ; Norovirus/*genetics/isolation & purification ; Seasons ; }, abstract = {In the winter season 2014/15, the GII.P17_GII.17 norovirus strain Kawasaki 2014 emerged in Italy, cocirculating with pandemic GII.4 strains. In March 2016, molecular investigation identified novel GII.P16 recombinant noroviruses in children with gastroenteritis in Italy. In 43.10% of the genotyped noroviruses GII.P16 strains were identified: 12 were characterized as GII.2 and 13 as GII.4 Sydney 2012 capsid genotypes. The GII.P16 genotype became predominant in January- February 2017 along with an increase in norovirus activity. The capsid gene was characterized as GII.2 or GII.4 Sydney 2012 variant. The emergence of two different recombinant GII.P16 viruses, of which one harboring a pandemic GII.4 capsid sequence, suggests the potential for a future pandemic.}, } @article {pmid29505066, year = {2018}, author = {Grancini, A and Orlandi, A and Lunghi, G and Consonni, D and Pozzi, C and Rossetti, V and Palleschi, A and Fracchiolla, N and Melada, E and Savioli, M and Arghittu, M and Maiavacca, R and Prigitano, A}, title = {Evaluation of Real Time PCR Aspergillus spp. in bronchoalveolar lavage samples.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {67-70}, pmid = {29505066}, issn = {1121-7138}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Aspergillus/*isolation & purification ; Bronchoalveolar Lavage Fluid/*microbiology ; Child ; DNA, Fungal/genetics/isolation & purification ; Humans ; Middle Aged ; Pulmonary Aspergillosis/*diagnosis ; Real-Time Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; Young Adult ; }, abstract = {The present study investigated the improvement in the diagnosis of invasive pulmonary aspergillosis (IPA) adding a molecular test on bronchoalveolar lavage (BAL) to the routine diagnostic approach including microscopy, culture and galactomannan (GM) immunoassay. A total of 133 BAL samples were retrospectively tested for the Aspergillus DNA: 112 samples were from immunocompromised patients at risk of invasive fungal infection and 21 were from patients not at risk and without clinical evidence of IPA. The latter samples were used to identify the cut-off of positivity for the molecular test. Applying the cut-off quantity of 50 copies/reaction, the PCR test had 90% sensitivity and 97% specificity and resulted the most sensitive, specific and accurate among those evaluated. The statistical analysis showed that the probability that a patient is not affected by IPA is 99% when the three tests (PCR, GM and culture) are concordantly negative.}, } @article {pmid29505065, year = {2018}, author = {Toljić, B and Trbovich, AM and Petrović, SM and Kannosh, IY and Dragović, G and Jevtović, D and De Luka, SR and Ristić-Djurović, JL and Milašin, J}, title = {Ageing with HIV - a periodontal perspective.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {61-66}, pmid = {29505065}, issn = {1121-7138}, mesh = {Adult ; Aged ; Aging/*physiology ; Anti-HIV Agents/therapeutic use ; Antiretroviral Therapy, Highly Active ; HIV Infections/*complications/drug therapy ; Humans ; Male ; Middle Aged ; Periodontal Diseases/etiology/*microbiology ; }, abstract = {The importance of oral microflora composition in HIV-infected patients is well recognized. However, no studies so far have dealt with age-related changes in periodontal pathogens occurrence in HIV+ individuals. The aim of the present study was to assess and compare temporal changes of bacteria frequency in younger (≤35 years) and older (≥50 years) HIV-infected and non-infected individuals. Bacterial DNA was isolated from buccal swabs of 30 younger and 30 older subjects in both HIV+ and HIV- groups. By means of PCR the following microorganisms were detected: Aggregatibacter actinomycetemcomitans, Eikenella corrodens, Peptostreptococcus micros, Porphyromonas gingivalis, Prevotella intermedia, Tannerella forsythia and Treponema denticola. Oral and periodontal examinations were performed in all subjects. The prevalence of microorganisms was significantly higher in HIV+ patients compared to controls, and their distribution showed a notable shift. The decreasing incidence in HIV- subjects was: Pi>Pm>Pg>Aa>Ec>Tf>Td whilst in HIV+ it was: Pi>Pm>Ec>Pg>Tf>Aa>Td. Oral manifestations of HIV infection were more frequent in older compared to younger patients. All measured values of clinical periodontal parameters were significantly higher in older compared to younger HIV+ patients. Ageing in HIV+ subjects is accompanied with a substantial increase and rearrangements of periodontal microflora, potentially aggravating oral and systemic health.}, } @article {pmid29505064, year = {2018}, author = {Sonoi, N and Maeda, H and Murauchi, T and Yamamoto, T and Omori, K and Kokeguchi, S and Naruishi, K and Takashiba, S}, title = {IS1598 (IsPg4) distributed to abscess-forming strains of Porphyromonas gingivalis may enhance virulence through upregulation of nrdD-like gene expression.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {52-60}, pmid = {29505064}, issn = {1121-7138}, mesh = {Abscess/microbiology ; Bacterial Proteins/genetics/*metabolism ; Gene Expression Regulation, Enzymologic ; Genes, Bacterial ; Genome, Bacterial ; Humans ; Mutagenesis, Insertional ; Porphyromonas gingivalis/*classification/*pathogenicity ; RNA, Messenger/genetics/metabolism ; Ribonucleotide Reductases/genetics/*metabolism ; Up-Regulation/*physiology ; Virulence ; }, abstract = {An insertion sequence, IS1598 (IsPg4) has been found in virulent strains of Porphyromonas gingivalis in a murine abscess model. The present study was performed to investigate the effects of genetic rearrangements by IS1598 on the phenotypic characteristics of the virulent strains. For this purpose, we searched for a common insertion site of IS1598 among the virulent strains. Through cloning and database search, a common insertion site was identified beside an nrdD-like gene in the virulent FDC 381, W83 and W50 strains. In this region, predicted promoters of the nrdD-like gene and IS1598 are located in tandem, and accumulation of nrdD-like gene mRNA was 5-fold higher in virulent strains (W83, W50, FDC 381) than avirulent strains (ATCC33277, SU63, SUNY1021, ESO59 without IS1598). The role of the nrdD-like gene in virulence of P. gingivalis was investigated by constructing a nrdD-deficient mutant. In the murine abscess model, the parental W83 strain produced necrotic abscesses, while the nrdD-deficient mutant had almost lost this ability. Insertion of IS1598 into the nrdD-like gene promoter region may be related to the phenotypic differences in virulence among P. gingivalis strains through upregulation of the expression of this gene.}, } @article {pmid29504931, year = {2018}, author = {Park, S and Choi, J and Park, JM and Yoon, JH}, title = {Aestuariimonas insulae gen. nov., sp. nov., isolated from a tidal flat.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1365-1371}, doi = {10.1099/ijsem.0.002684}, pmid = {29504931}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated OITF-44T, was isolated from a tidal flat in Oido, an island of the Republic of Korea. Strain OITF-44T grew optimally at 25 °C and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain OITF-44T formed an independent lineage within the clade comprising the genera Lutimonas, Taeania, Actibacter and Namhaeicola. The novel strain exhibited 16S rRNA gene sequence similarity values of 93.9-95.7 % to the type strains of the species of the genera Lutimonas, Taeania, Actibacter and Namhaeicola, and of less than 93.5 % to the type strains of other recognized species. Strain OITF-44T contained MK-6 as the predominant menaquinone and iso-C15 : 0, iso-C15 : 1 G, iso-C16 : 1 H and iso-C16 : 0 3-OH as the major fatty acids. The major polar lipids of strain OITF-44T were phosphatidylethanolamine, one unidentified lipid and one unidentified phospholipid. The DNA G+C content of strain OITF-44T was 33.9 mol%. The chemotaxonomic data and other differential phenotypic properties made it reasonable to distinguish strain OITF-44T from the type strains of the type species of the genera Lutimonas, Taeania, Actibacter and Namhaeicola. On the basis of the data presented here, strain OITF-44T is considered to constitute a new genus and species within the family Flavobacteriaceae, for which the name Aestuariimonas insulae gen. nov., sp. nov. is proposed. The type strain of Aestuariimonas insulae is OITF-44T (=KACC 19569T=KCTC 62197T=DSM 105891T=NBRC 113118T).}, } @article {pmid29504929, year = {2018}, author = {Park, S and Park, JM and Choi, SJ and Choi, J and Yoon, JH}, title = {Pseudomaribius aestuariivivens gen. nov., sp. nov., isolated from a tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1344-1349}, doi = {10.1099/ijsem.0.002677}, pmid = {29504929}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phosphatidylcholines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-motile and ovoid or rod-shaped bacterial strain, DBTF-15T, was isolated from a tidal flat sediment on the Yellow Sea in South Korea. Strain DBTF-15T grew optimally at 25-30 °C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain DBTF-15T joined the cluster comprising the type strains of species of the genus Palleronia. Strain DBTF-15T exhibited higher 16S rRNA gene sequence similarity values to the type strains (96.5-96.7 %) of Maribius pelagius and Maribius salinus than to those (94.6-96.1 %) of the three species of the genus Palleronia. It exhibited 16S rRNA gene sequence similarity values of less than 93.9 % to the type strains of the other recognized species. Strain DBTF-15T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c as the major fatty acid. The major polar lipids of strain DBTF-15T were phosphatidylcholine, phosphatidylglycerol and one unidentified aminolipid. The DNA G+C content of strain DBTF-15T was 68.7 mol%. The chemotaxonomic data and other differential phenotypic properties made it possible to distinguish strain DBTF-15T from the genera Maribius and Palleronia. On the basis of the data presented, strain DBTF-15T constitutes a novel genus and species within the class Alphaproteobacteria, for which the name Pseudomaribius aestuariivivens gen. nov., sp. nov. is proposed. The type strain is DBTF-15T (=KACC 19431T=NBRC 113039T).}, } @article {pmid29504928, year = {2018}, author = {Sheu, SY and Hsieh, TY and Kwon, SW and Chen, WM}, title = {Hymenobacter rivuli sp. nov., isolated from a freshwater creek.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1220-1226}, doi = {10.1099/ijsem.0.002657}, pmid = {29504928}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/chemistry ; Taiwan ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A bright-red bacterial strain, TAPP3T, was isolated from a freshwater sample taken from the Wanan Creek in Taiwan. Phylogenetic analyses based on 16S rRNA gene sequences revealed that TAPP3T represented a member of the genus Hymenobacter and showed the highest levels of sequence similarity to Hymenobacter ginsengisoli DCY57T (97.0 %) and Hymenobacter marinus KJ035T (96.5 %) and less than 96.2 % with other members of the genus. Cells of TAPP3T were Gram-stain-negative, aerobic, motile by gliding, rods that were surrounded by a thick capsule. Growth occurred at 20-35 °C (optimum, 25-30 °C), at pH 6.5-7.5 (optimum, pH 7) and with 0-1 % NaCl (optimum, 0 %). TAPP3T contained iso-C15 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 1ω5c as the predominant fatty acids. The major isoprenoid quinone was MK-7. The polar lipid profile consisted of phosphatidylethanolamine, six uncharacterized aminophospholipids and four uncharacterized lipids. The major polyamine was homospermidine. The DNA G+C content of the genomic DNA was 62.8 mol%. The DNA-DNA relatedness of TAPP3T with respect to Hymenobacter ginsengisoli DCY57T was less than 40 %. On the basis of the phylogenetic inference and phenotypic data, TAPP3T should be classified as representing a novel species, for which the name Hymenobacter rivuli sp. nov. is proposed. The type strain is TAPP3T (=BCRC 80979T=LMG 29559T=KCTC 52236T).}, } @article {pmid29504926, year = {2018}, author = {Szeinbaum, N and Kellum, CE and Glass, JB and Janda, JM and DiChristina, TJ}, title = {Whole-genome sequencing reveals that Shewanella haliotis Kim et al. 2007 can be considered a later heterotypic synonym of Shewanella algae Simidu et al. 1990.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1356-1360}, doi = {10.1099/ijsem.0.002678}, pmid = {29504926}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; *Genome, Bacterial ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Shewanella/*classification ; Whole Genome Sequencing ; }, abstract = {Previously, experimental DNA-DNA hybridization (DDH) between Shewanellahaliotis JCM 14758T and Shewanellaalgae JCM 21037T had suggested that the two strains could be considered different species, despite minimal phenotypic differences. The recent isolation of Shewanella sp. MN-01, with 99 % 16S rRNA gene identity to S. algae and S. haliotis, revealed a potential taxonomic problem between these two species. In this study, we reassessed the nomenclature of S. haliotis and S. algae using available whole-genome sequences. The whole-genome sequence of S. haliotis JCM 14758T and ten S. algae strains showed ≥97.7 % average nucleotide identity and >78.9 % digital DDH, clearly above the recommended species thresholds. According to the rules of priority and in view of the results obtained, S. haliotis is to be considered a later heterotypic synonym of S. algae. Because the whole-genome sequence of Shewanella sp. strain MN-01 shares >99 % ANI with S. algae JCM 14758T, it can be confidently identified as S. algae.}, } @article {pmid29504923, year = {2018}, author = {Park, M and Song, J and Nam, GG and Joung, Y and Zhao, L and Kim, MK and Cho, JC}, title = {Deinococcus lacus sp. nov., a gamma radiation-resistant bacterium isolated from an artificial freshwater pond.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1372-1377}, doi = {10.1099/ijsem.0.002683}, pmid = {29504923}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Deinococcus/*classification/isolation & purification/radiation effects ; Fatty Acids/chemistry ; *Gamma Rays ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Ponds/*microbiology ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A Gram-stain-negative, pink-coloured, non-motile and gamma radiation-resistant bacterium, designated strain IMCC1711T, was isolated from a freshwater sample collected from an artificial pond (Inkyong Pond). The 16S rRNA gene sequence analysis showed that strain IMCC1711T was most closely related to Deinococcus piscis 3axT (94.2 %) and formed a robust phylogenetic clade with other species of the genus Deinococcus. Optimal growth of strain MCC1711T was observed at 25 °C and pH 7.0 without NaCl. Strain IMCC1711T exhibited high resistance to gamma radiation. The DNA G+C content of strain IMCC1711T was 59.1 mol% and MK-8 was the predominant isoprenoid quinone. Major fatty acid constituents of the strain were C17 : 1ω8c, C16 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and C15 : 1ω6c. The major polar lipids constituted phosphatidylethanolamine, one unidentified phosphoglycolipid and two unidentified glycolipids. On the basis of taxonomic data obtained in this study, it was concluded that strain IMCC1711T represented a novel species of the genus Deinococcus, for which the name Deinococcus lacus sp. nov. is proposed. The type strain of Deinococcus lacus is IMCC1711T (KCTC 52494T=KACC 18979T=NBRC 112440T).}, } @article {pmid29504921, year = {2018}, author = {Park, S and Choi, J and Won, SM and Park, JM and Yoon, JH}, title = {Aestuariibius insulae gen. nov., sp. nov., isolated from a tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1350-1355}, doi = {10.1099/ijsem.0.002679}, pmid = {29504921}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-motile and ovoid or rod-shaped bacterial strain, DBTF-13T, which was isolated from a tidal flat sediment of the Yellow Sea in South Korea, was characterized taxonomically. Strain DBTF-13T grew optimally at 25-30 °C and pH 7.0-8.0, and in the presence of 2.0 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain DBTF-13T formed an evolutionary lineage independent of other genera, including the genera Pseudooctadecabacter and Octadecabacter. Strain DBTF-13T exhibited 16S rRNA gene sequence similarity values of 96.9 % to the type strain of Pseudooctadecabacter jejudonensis, and of 95.8-96.5 % to the type strains of Octadecabacter species. Strain DBTF-13T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c and C16 : 0 as the major fatty acids. The major polar lipids of strain DBTF-13T were phosphatidylcholine, phosphatidylglycerol, one unidentified aminolipid and one unidentified lipid. The DNA G+C content of strain DBTF-13T was 61.6 mol%. The chemotaxonomic data and other differential phenotypic properties made it reasonable to differentiate strain DBTF-13T from the genera Pseudooctadecabacter and Octadecabacter. On the basis of the data presented, strain DBTF-13T constitutes a new genus and species within the class Alphaproteobacteria, for which the name Aestuariibius insulae gen. nov., sp. nov. is proposed. The type strain is DBTF-13T (=KACC 19432T=NBRC 113038T).}, } @article {pmid29504920, year = {2018}, author = {Busse, HJ and Moore, ERB}, title = {Reclassification of Arthrobacter nasiphocae (Collins et al. 2002) as Falsarthrobacter nasiphocae gen. nov., comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1361-1364}, doi = {10.1099/ijsem.0.002680}, pmid = {29504920}, issn = {1466-5034}, mesh = {Arthrobacter/*classification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {The original description of Arthrobacter nasiphocae M597/99/10T demonstrated that it is distantly related to the type species of the genus Arthrobacter, Arthrobacter globiformis, and that this phylogenetic relationship is reflected by the distinct peptidoglycan type [Lys-Ala2-Gly2-3-Ala(Gly)] and the features of the quinone system, which is composed of menaquinones MK-9(H2) and MK-8(H2). Here, we report a re-evaluation of the taxonomic status of A. nasiphocae. Phylogenetically, it was observed to be only distantly related to the genus Arthrobacter and to the type species of related genera. Re-analysis confirmed the quinone system menaquinones MK-9(H2) and MK-8(H2) in A. nasiphocae. Analysis of cell polar lipids showed a profile consisting of the predominant lipids diphosphatidylglycerol, phosphatidylglycerol, dimannosylglyceride, an unidentified phospholipid and an unidentified aminophosphoglycolipid, and several minor unidentified lipids. This profile clearly is different from that of Arthrobacter species. The cell fatty acid profile also showed characteristics that distinguished A. nasiphocae from Arthrobacter species. The phylogenetic distance of A. nasiphocae from any type species of genera within the family Micrococcaceae and the distinct chemotaxonomic traits warrant the reclassification of A. nasiphocae within a novel genus, for which we propose the name Falsarthrobacter nasiphocae gen. nov., comb. nov. The type strain is M597/99/10T (=CCUG 42953T=CIP 107054T=DSM 13988T=JCM 11677T).}, } @article {pmid29504918, year = {2018}, author = {Orlov, YL and Baranova, AV and Hofestädt, R and Kolchanov, NA}, title = {Genomics at Belyaev conference - 2017.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {79}, pmid = {29504918}, issn = {1471-2164}, mesh = {*Genomics ; Systems Biology ; }, } @article {pmid29504917, year = {2018}, author = {Hagio, T and Sakuraba, S and Iwakiri, J and Mori, R and Asai, K}, title = {Capturing alternative secondary structures of RNA by decomposition of base-pairing probabilities.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {38}, pmid = {29504917}, issn = {1471-2105}, abstract = {BACKGROUND: It is known that functional RNAs often switch their functions by forming different secondary structures. Popular tools for RNA secondary structures prediction, however, predict the single 'best' structures, and do not produce alternative structures. There are bioinformatics tools to predict suboptimal structures, but it is difficult to detect which alternative secondary structures are essential.

RESULTS: We proposed a new computational method to detect essential alternative secondary structures from RNA sequences by decomposing the base-pairing probability matrix. The decomposition is calculated by a newly implemented software tool, RintW, which efficiently computes the base-pairing probability distributions over the Hamming distance from arbitrary reference secondary structures. The proposed approach has been demonstrated on ROSE element RNA thermometer sequence and Lysine RNA ribo-switch, showing that the proposed approach captures conformational changes in secondary structures.

CONCLUSIONS: We have shown that alternative secondary structures are captured by decomposing base-paring probabilities over Hamming distance. Source code is available from http://www.ncRNA.org/RintW .}, } @article {pmid29504911, year = {2018}, author = {Ershov, NI and Bondar, NP and Lepeshko, AA and Reshetnikov, VV and Ryabushkina, JA and Merkulova, TI}, title = {Consequences of early life stress on genomic landscape of H3K4me3 in prefrontal cortex of adult mice.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {93}, pmid = {29504911}, issn = {1471-2164}, mesh = {Adaptation, Psychological ; Animals ; Behavior, Animal ; Emotions ; Female ; *Genomics ; Histones/*chemistry/*metabolism ; Lysine/*metabolism ; Male ; *Maternal Deprivation ; Methylation ; Mice ; Mice, Inbred C57BL ; Prefrontal Cortex/*metabolism ; Stress, Psychological/*genetics/physiopathology/psychology ; }, abstract = {BACKGROUND: Maternal separation models in rodents are widely used to establish molecular mechanisms underlying prolonged effects of early life adversity on neurobiological and behavioral outcomes in adulthood. However, global epigenetic signatures following early life stress in these models remain unclear.

RESULTS: In this study, we carried out a ChIP-seq analysis of H3K4 trimethylation profile in the prefrontal cortex of adult male mice with a history of early life stress. Two types of stress were used: prolonged separation of pups from their mothers (for 3 h once a day, maternal separation, MS) and brief separation (for 15 min once a day, handling, HD). Adult offspring in the MS group demonstrated reduced locomotor activity in the open field test accompanied by reduced exploratory activity, while the HD group showed decreased anxiety-like behavior only. In a group of maternal separation, we have found a small number (45) of slightly up-regulated peaks, corresponding to promoters of 70 genes, while no changes were observed in a group of handling. Among the genes whose promoters have differential enrichment of H3K4me3, the most relevant ones participate in gene expression regulation, modulation of chromatin structure and mRNA processing. For two genes, Ddias and Pip4k2a, increased H3K4me3 levels were associated with the increased mRNA expression in MS group.

CONCLUSION: The distribution of H3K4me3 in prefrontal cortex showed relatively low variability across all individuals, and only some subtle changes were revealed in mice with a history of early life stress. It is possible that the observed long-lasting behavioral alterations induced by maternal separation are mediated by other epigenetic mechanisms, or other brain structures are responsible for these effects.}, } @article {pmid29504910, year = {2018}, author = {Kim, I and Choi, S and Kim, S}, title = {BRCA-Pathway: a structural integration and visualization system of TCGA breast cancer data on KEGG pathways.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {42}, pmid = {29504910}, issn = {1471-2105}, abstract = {BACKGROUND: Bioinformatics research for finding biological mechanisms can be done by analysis of transcriptome data with pathway based interpretation. Therefore, researchers have tried to develop tools to analyze transcriptome data with pathway based interpretation. Over the years, the amount of omics data has become huge, e.g., TCGA, and the data types to be analyzed have come in many varieties, including mutations, copy number variations, and transcriptome. We also need to consider a complex relationship with regulators of genes, particularly Transcription Factors(TF). However, there has not been a system for pathway based exploration and analysis of TCGA multi-omics data. In this reason, We have developed a web based system BRCA-Pathway to fulfill the need for pathway based analysis of TCGA multi-omics data.

RESULTS: BRCA-Pathway is a structured integration and visual exploration system of TCGA breast cancer data on KEGG pathways. For data integration, a relational database is designed and used to integrate multi-omics data of TCGA-BRCA, KEGG pathway data, Hallmark gene sets, transcription factors, driver genes, and PAM50 subtypes. For data exploration, multi-omics data such as SNV, CNV and gene expression can be visualized simultaneously in KEGG pathway maps, together with transcription factors-target genes (TF-TG) correlation and relationships among cancer driver genes. In addition, 'Pathways summary' and 'Oncoprint' with mutual exclusivity sort can be generated dynamically with a request by the user. Data in BRCA-Pathway can be downloaded by REST API for further analysis.

CONCLUSIONS: BRCA-Pathway helps researchers navigate omics data towards potentially important genes, regulators, and discover complex patterns involving mutations, CNV, and gene expression data of various patient groups in the biological pathway context. In addition, mutually exclusive genomic alteration patterns in a specific pathway can be generated. BRCA-Pathway can provide an integrative perspective on the breast cancer omics data, which can help researchers discover new insights on the biological mechanisms of breast cancer.}, } @article {pmid29504909, year = {2018}, author = {Suzuki, H and Kasahara, M}, title = {Introducing difference recurrence relations for faster semi-global alignment of long sequences.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {45}, pmid = {29504909}, issn = {1471-2105}, abstract = {BACKGROUND: The read length of single-molecule DNA sequencers is reaching 1 Mb. Popular alignment software tools widely used for analyzing such long reads often take advantage of single-instruction multiple-data (SIMD) operations to accelerate calculation of dynamic programming (DP) matrices in the Smith-Waterman-Gotoh (SWG) algorithm with a fixed alignment start position at the origin. Nonetheless, 16-bit or 32-bit integers are necessary for storing the values in a DP matrix when sequences to be aligned are long; this situation hampers the use of the full SIMD width of modern processors.

RESULTS: We proposed a faster semi-global alignment algorithm, "difference recurrence relations," that runs more rapidly than the state-of-the-art algorithm by a factor of 2.1. Instead of calculating and storing all the values in a DP matrix directly, our algorithm computes and stores mainly the differences between the values of adjacent cells in the matrix. Although the SWG algorithm and our algorithm can output exactly the same result, our algorithm mainly involves 8-bit integer operations, enabling us to exploit the full width of SIMD operations (e.g., 32) on modern processors. We also developed a library, libgaba, so that developers can easily integrate our algorithm into alignment programs.

CONCLUSIONS: Our novel algorithm and optimized library implementation will facilitate accelerating nucleotide long-read analysis algorithms that use pairwise alignment stages. The library is implemented in the C programming language and available at https://github.com/ocxtal/libgaba .}, } @article {pmid29504907, year = {2018}, author = {Pudova, EA and Kudryavtseva, AV and Fedorova, MS and Zaretsky, AR and Shcherbo, DS and Lukyanova, EN and Popov, AY and Sadritdinova, AF and Abramov, IS and Kharitonov, SL and Krasnov, GS and Klimina, KM and Koroban, NV and Volchenko, NN and Nyushko, KM and Melnikova, NV and Chernichenko, MA and Sidorov, DV and Alekseev, BY and Kiseleva, MV and Kaprin, AD and Dmitriev, AA and Snezhkina, AV}, title = {HK3 overexpression associated with epithelial-mesenchymal transition in colorectal cancer.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {113}, pmid = {29504907}, issn = {1471-2164}, mesh = {Colorectal Neoplasms/*genetics/*pathology ; Epithelial-Mesenchymal Transition/*genetics ; Female ; Gene Expression Profiling ; Genomics ; Hexokinase/*genetics ; Humans ; Male ; Middle Aged ; Up-Regulation ; }, abstract = {BACKGROUND: Colorectal cancer (CRC) is a common cancer worldwide. The main cause of death in CRC includes tumor progression and metastasis. At molecular level, these processes may be triggered by epithelial-mesenchymal transition (EMT) and necessitates specific alterations in cell metabolism. Although several EMT-related metabolic changes have been described in CRC, the mechanism is still poorly understood.

RESULTS: Using CrossHub software, we analyzed RNA-Seq expression profile data of CRC derived from The Cancer Genome Atlas (TCGA) project. Correlation analysis between the change in the expression of genes involved in glycolysis and EMT was performed. We obtained the set of genes with significant correlation coefficients, which included 21 EMT-related genes and a single glycolytic gene, HK3. The mRNA level of these genes was measured in 78 paired colorectal cancer samples by quantitative polymerase chain reaction (qPCR). Upregulation of HK3 and deregulation of 11 genes (COL1A1, TWIST1, NFATC1, GLIPR2, SFPR1, FLNA, GREM1, SFRP2, ZEB2, SPP1, and RARRES1) involved in EMT were found. The results of correlation study showed that the expression of HK3 demonstrated a strong correlation with 7 of the 21 examined genes (ZEB2, GREM1, TGFB3, TGFB1, SNAI2, TWIST1, and COL1A1) in CRC.

CONCLUSIONS: Upregulation of HK3 is associated with EMT in CRC and may be a crucial metabolic adaptation for rapid proliferation, survival, and metastases of CRC cells.}, } @article {pmid29504906, year = {2018}, author = {Salina, EA and Nesterov, MA and Frenkel, Z and Kiseleva, AA and Timonova, EM and Magni, F and Vrána, J and Šafář, J and Šimková, H and Doležel, J and Korol, A and Sergeeva, EM}, title = {Features of the organization of bread wheat chromosome 5BS based on physical mapping.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {80}, pmid = {29504906}, issn = {1471-2164}, mesh = {*Bread ; Chromosomes, Artificial, Bacterial/genetics ; Chromosomes, Plant/*genetics ; *Physical Chromosome Mapping ; Polymerase Chain Reaction ; Triticum/*genetics ; }, abstract = {BACKGROUND: The IWGSC strategy for construction of the reference sequence of the bread wheat genome is based on first obtaining physical maps of the individual chromosomes. Our aim is to develop and use the physical map for analysis of the organization of the short arm of wheat chromosome 5B (5BS) which bears a number of agronomically important genes, including genes conferring resistance to fungal diseases.

RESULTS: A physical map of the 5BS arm (290 Mbp) was constructed using restriction fingerprinting and LTC software for contig assembly of 43,776 BAC clones. The resulting physical map covered ~ 99% of the 5BS chromosome arm (111 scaffolds, N50 = 3.078 Mb). SSR, ISBP and zipper markers were employed for anchoring the BAC clones, and from these 722 novel markers were developed based on previously obtained data from partial sequencing of 5BS. The markers were mapped using a set of Chinese Spring (CS) deletion lines, and F2 and RICL populations from a cross of CS and CS-5B dicoccoides. Three approaches have been used for anchoring BAC contigs on the 5BS chromosome, including clone-by-clone screening of BACs, GenomeZipper analysis, and comparison of BAC-fingerprints with in silico fingerprinting of 5B pseudomolecules of T. dicoccoides. These approaches allowed us to reach a high level of BAC contig anchoring: 96% of 5BS BAC contigs were located on 5BS. An interesting pattern was revealed in the distribution of contigs along the chromosome. Short contigs (200-999 kb) containing markers for the regions interrupted by tandem repeats, were mainly localized to the 5BS subtelomeric block; whereas the distribution of larger 1000-3500 kb contigs along the chromosome better correlated with the distribution of the regions syntenic to rice, Brachypodium, and sorghum, as detected by the Zipper approach.

CONCLUSION: The high fingerprinting quality, LTC software and large number of BAC clones selected by the informative markers in screening of the 43,776 clones allowed us to significantly increase the BAC scaffold length when compared with the published physical maps for other wheat chromosomes. The genetic and bioinformatics resources developed in this study provide new possibilities for exploring chromosome organization and for breeding applications.}, } @article {pmid29504905, year = {2018}, author = {Ko, G and Kim, PG and Yoon, J and Han, G and Park, SJ and Song, W and Lee, B}, title = {Closha: bioinformatics workflow system for the analysis of massive sequencing data.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {43}, pmid = {29504905}, issn = {1471-2105}, abstract = {BACKGROUND: While next-generation sequencing (NGS) costs have fallen in recent years, the cost and complexity of computation remain substantial obstacles to the use of NGS in bio-medical care and genomic research. The rapidly increasing amounts of data available from the new high-throughput methods have made data processing infeasible without automated pipelines. The integration of data and analytic resources into workflow systems provides a solution to the problem by simplifying the task of data analysis.

RESULTS: To address this challenge, we developed a cloud-based workflow management system, Closha, to provide fast and cost-effective analysis of massive genomic data. We implemented complex workflows making optimal use of high-performance computing clusters. Closha allows users to create multi-step analyses using drag and drop functionality and to modify the parameters of pipeline tools. Users can also import the Galaxy pipelines into Closha. Closha is a hybrid system that enables users to use both analysis programs providing traditional tools and MapReduce-based big data analysis programs simultaneously in a single pipeline. Thus, the execution of analytics algorithms can be parallelized, speeding up the whole process. We also developed a high-speed data transmission solution, KoDS, to transmit a large amount of data at a fast rate. KoDS has a file transfer speed of up to 10 times that of normal FTP and HTTP. The computer hardware for Closha is 660 CPU cores and 800 TB of disk storage, enabling 500 jobs to run at the same time.

CONCLUSIONS: Closha is a scalable, cost-effective, and publicly available web service for large-scale genomic data analysis. Closha supports the reliable and highly scalable execution of sequencing analysis workflows in a fully automated manner. Closha provides a user-friendly interface to all genomic scientists to try to derive accurate results from NGS platform data. The Closha cloud server is freely available for use from http://closha.kobic.re.kr/ .}, } @article {pmid29504903, year = {2018}, author = {Lee, T and Lee, S and Sim, WY and Jung, YM and Han, S and Won, JH and Min, H and Yoon, S}, title = {HiComet: a high-throughput comet analysis tool for large-scale DNA damage assessment.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {44}, pmid = {29504903}, issn = {1471-2105}, abstract = {BACKGROUND: DNA damage causes aging, cancer, and other serious diseases. The comet assay can detect multiple types of DNA lesions with high sensitivity, and it has been widely applied. Although comet assay platforms have improved the limited throughput and reproducibility of traditional assays in recent times, analyzing large quantities of comet data often requires a tremendous human effort. To overcome this challenge, we proposed HiComet, a computational tool that can rapidly recognize and characterize a large number of comets, using little user intervention.

RESULTS: We tested HiComet with real data from 35 high-throughput comet assay experiments, with over 700 comets in total. The proposed method provided unprecedented levels of performance as an automated comet recognition tool in terms of robustness (measured by precision and recall) and throughput.

CONCLUSIONS: HiComet is an automated tool for high-throughput comet-assay analysis and could significantly facilitate characterization of individual comets by accelerating its most rate-limiting step. An online implementation of HiComet is freely available at https://github.com/taehoonlee/HiComet/ .}, } @article {pmid29504902, year = {2018}, author = {Choi, SW and Nam, JW}, title = {TERIUS: accurate prediction of lncRNA via high-throughput sequencing data representing RNA-binding protein association.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {41}, pmid = {29504902}, issn = {1471-2105}, abstract = {BACKGROUND: LncRNAs are long regulatory non-coding RNAs, some of which are arguably predicted to have coding potential. Despite coding potential classifiers that utilize ribosome profiling data successfully detected actively translated regions, they are less sensitive to lncRNAs. Furthermore, lncRNA annotation can be susceptible to false positives obtained from 3' untranslated region (UTR) fragments of mRNAs.

RESULTS: To lower these limitations in lncRNA annotation, we present a novel tool TERIUS that provides a two-step filtration process to distinguish between bona fide and false lncRNAs. The first step successfully separates lncRNAs from protein-coding genes showing enhanced sensitivity compared to other methods. To eliminate 3'UTR fragments, the second step takes advantage of the 3'UTR-specific association with regulator of nonsense transcripts 1 (UPF1), leading to refined lncRNA annotation. Importantly, TERIUS enabled the detection of misclassified transcripts in published lncRNA annotations.

CONCLUSIONS: TERIUS is a robust method for lncRNA annotation, which provides an additional filtration step for 3'UTR fragments. TERIUS was able to successfully re-classify GENCODE and miTranscriptome lncRNA annotations. We believe that TERIUS can benefit construction of extensive and accurate non-coding transcriptome maps in many genomes.}, } @article {pmid29504901, year = {2018}, author = {Stefanova, NA and Maksimova, KY and Rudnitskaya, EA and Muraleva, NA and Kolosova, NG}, title = {Association of cerebrovascular dysfunction with the development of Alzheimer's disease-like pathology in OXYS rats.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {75}, pmid = {29504901}, issn = {1471-2164}, mesh = {Aging/genetics/physiology ; Alzheimer Disease/genetics/*pathology/*physiopathology ; Amyloid beta-Peptides/metabolism ; Animals ; Blood Vessels/*physiopathology ; Gene Expression Profiling ; Gene Regulatory Networks ; Hippocampus/*blood supply ; Molecular Sequence Annotation ; Peptide Fragments/metabolism ; Rats ; Species Specificity ; Vascular Endothelial Growth Factor A/metabolism ; }, abstract = {BACKGROUND: Cerebrovascular dysfunction plays a critical role in the pathogenesis of Alzheimer's disease (AD): the most common cause of dementia in the elderly. The involvement of neurovasculature disorders in the progression of AD is now increasingly appreciated, but whether they represent initial factors or late-stage pathological changes during the disease is unclear. Using senescence-accelerated OXYS rats, which simulate key characteristics of sporadic AD, we evaluated contributions of cerebrovascular alterations to the disease development. At preclinical, early, and advanced stages of AD-like pathology, in the hippocampus of OXYS and Wistar (control) rats, we evaluated (i) the blood vessel state by histological and electron-microscopic analyses; (ii) differences in gene expression according to RNA sequencing (RNA-Seq) to identify the metabolic processes and pathways associated with blood vessel function; (iii) the amount of vascular endothelial growth factor (VEGF) by western blot and immunohistochemical analysis.

RESULTS: We observed a loss of hippocampal blood vessel density and ultrastructural changes of those blood vessels in OXYS rats at the early stage of AD-like pathology. There were significant alterations in the vessels and downregulation of VEGF with an increased amount of amyloid β1-42 there at the advanced stage of the disease. According to RNA-Seq data analysis, major alterations in cerebrovascular processes of OXYS rats were associated with blood vessel development, circulatory system processes, the VEGF signaling pathway, and vascular smooth muscle contraction. At preclinical and early stages of the AD-like pathology, these processes were upregulated and then downregulated with age. At the advanced stage in OXYS rats, differentially expressed genes (DEGs) were associated with downregulation of cerebrovascular function as compared to Wistar rats. Among the 46 DEGs at the preclinical stage of the disease, 28 DEGs at the early stage, and among 85 DEGs at the advanced stage, using functional analysis and gene network construction, we identified genes (Nos1, P2rx4, Pla2g6, and Bdkrb2) probably playing a significant role in the development of cerebrovascular dysfunction in OXYS rats.

CONCLUSIONS: Changes in expression of the genes functionally associated with cerebrovascular processes already in the early period of life may contribute to the development of AD-like pathology in OXYS rats.}, } @article {pmid29504899, year = {2018}, author = {Chadaeva, IV and Ponomarenko, PM and Rasskazov, DA and Sharypova, EB and Kashina, EV and Zhechev, DA and Drachkova, IA and Arkova, OV and Savinkova, LK and Ponomarenko, MP and Kolchanov, NA and Osadchuk, LV and Osadchuk, AV}, title = {Candidate SNP markers of reproductive potential are predicted by a significant change in the affinity of TATA-binding protein for human gene promoters.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {0}, pmid = {29504899}, issn = {1471-2164}, mesh = {Cell Line ; Female ; Genetic Markers/*genetics ; *Genomics ; Humans ; Internet ; Polymorphism, Single Nucleotide/*genetics ; Promoter Regions, Genetic/*genetics ; Protein Binding ; Reproduction/*genetics ; TATA-Box Binding Protein/*metabolism ; }, abstract = {BACKGROUND: The progress of medicine, science, technology, education, and culture improves, year by year, quality of life and life expectancy of the populace. The modern human has a chance to further improve the quality and duration of his/her life and the lives of his/her loved ones by bringing their lifestyle in line with their sequenced individual genomes. With this in mind, one of genome-based developments at the junction of personalized medicine and bioinformatics will be considered in this work, where we used two Web services: (i) SNP_TATA_Comparator to search for alleles with a single nucleotide polymorphism (SNP) that alters the affinity of TATA-binding protein (TBP) for the TATA boxes of human gene promoters and (ii) PubMed to look for retrospective clinical reviews on changes in physiological indicators of reproductive potential in carriers of these alleles.

RESULTS: A total of 126 SNP markers of female reproductive potential, capable of altering the affinity of TBP for gene promoters, were found using the two above-mentioned Web services. For example, 10 candidate SNP markers of thrombosis (e.g., rs563763767) can cause overproduction of coagulation inducers. In pregnant women, Hughes syndrome provokes thrombosis with a fatal outcome although this syndrome can be diagnosed and eliminated even at the earliest stages of its development. Thus, in women carrying any of the above SNPs, preventive treatment of this syndrome before a planned pregnancy can reduce the risk of death. Similarly, seven SNP markers predicted here (e.g., rs774688955) can elevate the risk of myocardial infarction. In line with Bowles' lifespan theory, women carrying any of these SNPs may modify their lifestyle to improve their longevity if they can take under advisement that risks of myocardial infarction increase with age of the mother, total number of pregnancies, in multiple pregnancies, pregnancies under the age of 20, hypertension, preeclampsia, menstrual cycle irregularity, and in women smokers.

CONCLUSIONS: According to Bowles' lifespan theory-which links reproductive potential, quality of life, and life expectancy-the above information was compiled for those who would like to reduce risks of diseases corresponding to alleles in own sequenced genomes. Candidate SNP markers can focus the clinical analysis of unannotated SNPs, after which they may become useful for people who would like to bring their lifestyle in line with their sequenced individual genomes.}, } @article {pmid29504898, year = {2018}, author = {Voronina, OL and Kunda, MS and Ryzhova, NN and Aksenova, EI and Sharapova, NE and Semenov, AN and Amelina, EL and Chuchalin, AG and Gintsburg, AL}, title = {On Burkholderiales order microorganisms and cystic fibrosis in Russia.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {74}, pmid = {29504898}, issn = {1471-2164}, mesh = {Adolescent ; Adult ; Aged ; Burkholderiales/*genetics/*physiology ; Child ; Child, Preschool ; Cystic Fibrosis/*microbiology ; Female ; Genetic Variation ; Humans ; Infant ; Male ; Microbiota ; Middle Aged ; Russia ; Young Adult ; }, abstract = {BACKGROUND: Microbes infecting cystic fibrosis patients' respiratory tract are important in determining patients' functional status. Representatives of Burkholderiales order are the most dangerous. The goal of our investigation was to reveal the diversity of Burkholderiales, define of their proportion in the microbiome of various parts of respiratory tract and determine the pathogenicity of the main representatives.

RESULTS: In more than 500 cystic fibrosis patients, representing all Federal Regions of Russia, 34.0% were infected by Burkholderia cepacia complex (Bcc), 21.0% by Achromobacter spp. and 12.0% by Lautropia mirabilis. B. cenocepacia was the most numerous species among the Bcc (93.0%), and A. ruhlandii was the most numerous among Achromobacter spp. (58.0%). The most abundant genotype in Bcc was sequence type (ST) 709, and in Achromobacter spp. it was ST36. These STs constitute Russian epidemic strains. Whole genome sequencing of strains A. ruhlandii SCCH3:Ach33-1365 ST36 and B. cenocepacia GIMC4560:Bcn122 ST709 revealed huge resistomes and many virulence factors, which may explain the difficulties in eradicating these strains. An experience of less dangerous B. cenocepcia ST710 elimination was described. Massively parallel sequencing of 16S rDNA amplicons, including V1-V4 hypervariable regions, was used to definite "healthy" microbiome characteristics. Analysis of maxillary sinus lavage of 7 patients revealed infection with Proteobacteria of the same ST as pathogens from sputum, suggesting that the maxillary sinus is a source of infection in cystic fibrosis patients.

CONCLUSIONS: Characterization of the Russian epidemic bacterial strains in the sputum and sinuses of cystic fibrosis patients have better defined the importance of Burkholderiales bacteria. This information may aid in the development of effective approaches for treatment of this disease.}, } @article {pmid29504897, year = {2018}, author = {Ruan, P and Hayashida, M and Akutsu, T and Vert, JP}, title = {Improving prediction of heterodimeric protein complexes using combination with pairwise kernel.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {39}, pmid = {29504897}, issn = {1471-2105}, support = {280032//European Research Council/International ; }, abstract = {BACKGROUND: Since many proteins become functional only after they interact with their partner proteins and form protein complexes, it is essential to identify the sets of proteins that form complexes. Therefore, several computational methods have been proposed to predict complexes from the topology and structure of experimental protein-protein interaction (PPI) network. These methods work well to predict complexes involving at least three proteins, but generally fail at identifying complexes involving only two different proteins, called heterodimeric complexes or heterodimers. There is however an urgent need for efficient methods to predict heterodimers, since the majority of known protein complexes are precisely heterodimers.

RESULTS: In this paper, we use three promising kernel functions, Min kernel and two pairwise kernels, which are Metric Learning Pairwise Kernel (MLPK) and Tensor Product Pairwise Kernel (TPPK). We also consider the normalization forms of Min kernel. Then, we combine Min kernel or its normalization form and one of the pairwise kernels by plugging. We applied kernels based on PPI, domain, phylogenetic profile, and subcellular localization properties to predicting heterodimers. Then, we evaluate our method by employing C-Support Vector Classification (C-SVC), carrying out 10-fold cross-validation, and calculating the average F-measures. The results suggest that the combination of normalized-Min-kernel and MLPK leads to the best F-measure and improved the performance of our previous work, which had been the best existing method so far.

CONCLUSIONS: We propose new methods to predict heterodimers, using a machine learning-based approach. We train a support vector machine (SVM) to discriminate interacting vs non-interacting protein pairs, based on informations extracted from PPI, domain, phylogenetic profiles and subcellular localization. We evaluate in detail new kernel functions to encode these data, and report prediction performance that outperforms the state-of-the-art.}, } @article {pmid29504896, year = {2018}, author = {Moskalev, A and Shaposhnikov, M and Zemskaya, N and Belyi, A and Dobrovolskaya, E and Patova, A and Guvatova, Z and Lukyanova, E and Snezhkina, A and Kudryavtseva, A}, title = {Transcriptome analysis reveals mechanisms of geroprotective effects of fucoxanthin in Drosophila.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {77}, pmid = {29504896}, issn = {1471-2164}, mesh = {Animals ; Caenorhabditis elegans/genetics/physiology ; Drosophila melanogaster/genetics/physiology ; Female ; Fertility/genetics ; *Gene Expression Profiling ; Intestinal Mucosa/metabolism ; Locomotion/genetics ; Longevity/*genetics ; Male ; Oxidative Stress/genetics ; Permeability ; Xanthophylls/*metabolism ; }, abstract = {BACKGROUND: We have previously showed that the carotenoid fucoxanthin can increase the lifespan in Drosophila melanogaster and Caenorhabditis elegans. However, the molecular mechanisms of the geroprotective effect of fucoxanthin have not been studied so far.

RESULTS: Here, we studied the effects of fucoxanthin on the Drosophila aging process at the molecular and the whole organism levels. At the organismal level, fucoxanthin increased the median lifespan and had a positive effect on fecundity, fertility, intestinal barrier function, and nighttime sleep. Transcriptome analysis revealed 57 differentially expressed genes involved in 17 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways. Among the most represented molecular pathways induced by fucoxanthin, a significant portion is related to longevity, including MAPK, mTOR, Wnt, Notch, and Hippo signaling pathways, autophagy, translation, glycolysis, oxidative phosphorylation, apoptosis, immune response, neurogenesis, sleep, and response to DNA damage.

CONCLUSIONS: Life-extending effects of fucoxanthin are associated with differential expression of longevity-associated genes.}, } @article {pmid29504895, year = {2018}, author = {Tiys, ES and Ivanisenko, TV and Demenkov, PS and Ivanisenko, VA}, title = {FunGeneNet: a web tool to estimate enrichment of functional interactions in experimental gene sets.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {76}, pmid = {29504895}, issn = {1471-2164}, mesh = {Apoptosis ; Databases, Genetic ; Gene Ontology ; *Gene Regulatory Networks ; Genomics/*methods ; Humans ; *Internet ; Thyroid Neoplasms/genetics/pathology ; }, abstract = {BACKGROUND: Estimation of functional connectivity in gene sets derived from genome-wide or other biological experiments is one of the essential tasks of bioinformatics. A promising approach for solving this problem is to compare gene networks built using experimental gene sets with random networks. One of the resources that make such an analysis possible is CrossTalkZ, which uses the FunCoup database. However, existing methods, including CrossTalkZ, do not take into account individual types of interactions, such as protein/protein interactions, expression regulation, transport regulation, catalytic reactions, etc., but rather work with generalized types characterizing the existence of any connection between network members.

RESULTS: We developed the online tool FunGeneNet, which utilizes the ANDSystem and STRING to reconstruct gene networks using experimental gene sets and to estimate their difference from random networks. To compare the reconstructed networks with random ones, the node permutation algorithm implemented in CrossTalkZ was taken as a basis. To study the FunGeneNet applicability, the functional connectivity analysis of networks constructed for gene sets involved in the Gene Ontology biological processes was conducted. We showed that the method sensitivity exceeds 0.8 at a specificity of 0.95. We found that the significance level of the difference between gene networks of biological processes and random networks is determined by the type of connections considered between objects. At the same time, the highest reliability is achieved for the generalized form of connections that takes into account all the individual types of connections. By taking examples of the thyroid cancer networks and the apoptosis network, it is demonstrated that key participants in these processes are involved in the interactions of those types by which these networks differ from random ones.

CONCLUSIONS: FunGeneNet is a web tool aimed at proving the functionality of networks in a wide range of sizes of experimental gene sets, both for different global networks and for different types of interactions. Using examples of thyroid cancer and apoptosis networks, we have shown that the links over-represented in the analyzed network in comparison with the random ones make possible a biological interpretation of the original gene/protein sets. The FunGeneNet web tool for assessment of the functional enrichment of networks is available at http://www-bionet.sscc.ru/fungenenet/ .}, } @article {pmid29504894, year = {2018}, author = {Yang, IS and Kim, S}, title = {Isoform specific gene expression analysis of KRAS in the prognosis of lung adenocarcinoma patients.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {40}, doi = {10.1186/s12859-018-2011-y}, pmid = {29504894}, issn = {1471-2105}, abstract = {BACKGROUND: Aberrant mutations in KRAS play a critical role in tumor initiation and progression, and are a negative prognosis factor in lung adenocarcinoma (LUAD).

RESULTS: Using genomic analysis for K-Ras isoforms (K-Ras4A and K-Ras4B) and large-scale multi-omics data, we inspected the overall survival (OS) and disease-free survival (DFS) of LUAD patients based on the abundance of transcript variants by analyzing RNA expression and somatic mutation data from The Cancer Genome Atlas (n = 516). The expression of the minor transcript K-Ras4A and its proportion were positively correlated with the presence of KRAS mutations in LUAD. We found that both K-Ras4A abundance measures (expression and proportion) have a strong association with poor OS (p = 0.0149 and p = 3.18E-3, respectively) and DFS (p = 3.03E-4 and p = 0.0237, respectively), but only in patients harboring KRAS mutations. A Cox regression analysis showed significant results in groups with low expression (hazard ratio (HR) = 2.533, 95% confidence interval (CI) = 1.380-4.651, p = 2.72E-3) and low proportion (HR = 2.549, 95% CI = 1.387-4.684, p = 2.58E-3) of K-Ras4A.

CONCLUSIONS: Based on the above results, we report the possible use of abundance measures for K-Ras4A for predicting the survival of LUAD patients with KRAS mutations.}, } @article {pmid29504893, year = {2018}, author = {Naumenko, FM and Abnizova, II and Beka, N and Genaev, MA and Orlov, YL}, title = {Novel read density distribution score shows possible aligner artefacts, when mapping a single chromosome.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {92}, pmid = {29504893}, issn = {1471-2164}, mesh = {*Artifacts ; Chromosome Mapping/*methods ; Genomics ; }, abstract = {BACKGROUND: The use of artificial data to evaluate the performance of aligners and peak callers not only improves its accuracy and reliability, but also makes it possible to reduce the computational time. One of the natural ways to achieve such time reduction is by mapping a single chromosome.

RESULTS: We investigated whether a single chromosome mapping causes any artefacts in the alignments' performances. In this paper, we compared the accuracy of the performance of seven aligners on well-controlled simulated benchmark data which was sampled from a single chromosome and also from a whole genome. We found that commonly used statistical methods are insufficient to evaluate an aligner performance, and applied a novel measure of a read density distribution similarity, which allowed to reveal artefacts in aligners' performances. We also calculated some interesting mismatch statistics, and constructed mismatch frequency distributions along the read.

CONCLUSIONS: The generation of artificial data by mapping of reads generated from a single chromosome to a reference chromosome is justified from the point of view of reducing the benchmarking time. The proposed quality assessment method allows to identify the inherent shortcoming of aligners that are not detected by conventional statistical methods, and can affect the quality of alignment of real data.}, } @article {pmid29504892, year = {2018}, author = {Titov, II and Vorozheykin, PS}, title = {Comparing miRNA structure of mirtrons and non-mirtrons.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 3}, pages = {114}, pmid = {29504892}, issn = {1471-2164}, mesh = {Animals ; Humans ; Introns/*genetics ; Mice ; MicroRNAs/*genetics ; Polymorphism, Single Nucleotide ; RNA Precursors/genetics ; RNA Splicing ; }, abstract = {BACKGROUND: MicroRNAs proceeds through the different canonical and non-canonical pathways; the most frequent of the non-canonical ones is the splicing-dependent biogenesis of mirtrons. We compare the mirtrons and non-mirtrons of human and mouse to explore how their maturation appears in the precursor structure around the miRNA.

RESULTS: We found the coherence of the overhang lengths what indicates the dependence between the cleavage sites. To explain this dependence we suggest the 2-lever model of the Dicer structure that couples the imprecisions in Drosha and Dicer. Considering the secondary structure of all animal pre-miRNAs we confirmed that single-stranded nucleotides tend to be located near the miRNA boundaries and in its center and are characterized by a higher mutation rate. The 5' end of the canonical 5' miRNA approaches the nearest single-stranded nucleotides what suggests the extension of the loop-counting rule from the Dicer to the Drosha cleavage site. A typical structure of the annotated mirtron pre-miRNAs differs from the canonical pre-miRNA structure and possesses the 1- and 2 nt hanging ends at the hairpin base. Together with the excessive variability of the mirtron Dicer cleavage site (that could be partially explained by guanine at its ends inherited from splicing) this is one more evidence for the 2-lever model. In contrast with the canonical miRNAs the mirtrons have higher snp densities and their pre-miRNAs are inversely associated with diseases. Therefore we supported the view that mirtrons are under positive selection while canonical miRNAs are under negative one and we suggested that mirtrons are an intrinsic source of silencing variability which produces the disease-promoting variants. Finally, we considered the interference of the pre-miRNA structure and the U2snRNA:pre-mRNA basepairing. We analyzed the location of the branchpoints and found that mirtron structure tends to expose the branchpoint site what suggests that the mirtrons can readily evolve from occasional hairpins in the immediate neighbourhood of the 3' splice site.

CONCLUSION: The miRNA biogenesis manifests itself in the footprints of the secondary structure. Close inspection of these structural properties can help to uncover new pathways of miRNA biogenesis and to refine the known miRNA data, in particular, new non-canonical miRNAs may be predicted or the known miRNAs can be re-classified.}, } @article {pmid29504891, year = {2018}, author = {Etemadi, M and Bagherian, M and Chen, ZZ and Wang, L}, title = {Better ILP models for haplotype assembly.}, journal = {BMC bioinformatics}, volume = {19}, number = {Suppl 1}, pages = {52}, doi = {10.1186/s12859-018-2012-x}, pmid = {29504891}, issn = {1471-2105}, abstract = {BACKGROUND: The haplotype assembly problem for diploid is to find a pair of haplotypes from a given set of aligned Single Nucleotide Polymorphism (SNP) fragments (reads). It has many applications in association studies, drug design, and genetic research. Since this problem is computationally hard, both heuristic and exact algorithms have been designed for it. Although exact algorithms are much slower, they are still of great interest because they usually output significantly better solutions than heuristic algorithms in terms of popular measures such as the Minimum Error Correction (MEC) score, the number of switch errors, and the QAN50 score. Exact algorithms are also valuable because they can be used to witness how good a heuristic algorithm is. The best known exact algorithm is based on integer linear programming (ILP) and it is known that ILP can also be used to improve the output quality of every heuristic algorithm with a little decline in speed. Therefore, faster ILP models for the problem are highly demanded.

RESULTS: As in previous studies, we consider not only the general case of the problem but also its all-heterozygous case where we assume that if a column of the input read matrix contains at least one 0 and one 1, then it corresponds to a heterozygous SNP site. For both cases, we design new ILP models for the haplotype assembly problem which aim at minimizing the MEC score. The new models are theoretically better because they contain significantly fewer constraints. More importantly, our experimental results show that for both simulated and real datasets, the new model for the all-heterozygous (respectively, general) case can usually be solved via CPLEX (an ILP solver) at least 5 times (respectively, twice) faster than the previous bests. Indeed, the running time can sometimes be 41 times better.

CONCLUSIONS: This paper proposes a new ILP model for the haplotype assembly problem and its all-heterozygous case, respectively. Experiments with both real and simulated datasets show that the new models can be solved within much shorter time by CPLEX than the previous bests. We believe that the models can be used to improve heuristic algorithms as well.}, } @article {pmid29504672, year = {2018}, author = {Béhague, J and Fisher, BL and Péronnet, R and Rajakumar, R and Abouheif, E and Molet, M}, title = {Lack of interruption of the gene network underlying wing polyphenism in an early-branching ant genus.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {2}, pages = {109-117}, doi = {10.1002/jez.b.22794}, pmid = {29504672}, issn = {1552-5015}, mesh = {Animals ; Ants/anatomy & histology/*genetics/*physiology ; *Biological Evolution ; Cloning, Molecular ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Wings, Animal/*anatomy & histology ; }, abstract = {Ants evolved about 140 million years ago and have diversified into more than 15,000 species with tremendous ecological and morphological diversity, yet evolution of the gene regulatory networks (GRNs) underlying this diversification remains poorly understood. Wing polyphenism, the ability of a single genome to produce either winged or wingless castes during development in response to environmental cues, is a nearly universal feature of ants. The underlying wing GRN is evolutionarily labile in worker castes of phylogenetically derived species: it is conserved in winged castes but interrupted at different points in wingless castes of different species. However, it remains unknown whether the wing GRN is interrupted in wingless castes of species from early branching lineages, and if so, whether it is interrupted at similar locations in worker castes of derived species. We therefore used in situ hybridization to assay the expression of nine genes in the wing GRN in wing imaginal discs of larvae from two species from the early branching ('basal') genus Mystrium. These species possess two castes each: Mystrium rogeri has winged queens and wingless workers, and M. oberthueri has wingless queens and wingless workers. In contrast to derived species, we found no evidence of interruption points in the wing GRN kernel of wingless castes. Our finding supports: (1) a "phylogenetic ladder model" of wing GRN evolution, where interruption points move further upstream in the wing GRN as ant lineages become more derived; and (2) that evolutionary lability of the GRN underlying wing polyphenism originated later during ant evolution.}, } @article {pmid29504240, year = {2018}, author = {van Kleunen, M and Essl, F and Pergl, J and Brundu, G and Carboni, M and Dullinger, S and Early, R and González-Moreno, P and Groom, QJ and Hulme, PE and Kueffer, C and Kühn, I and Máguas, C and Maurel, N and Novoa, A and Parepa, M and Pyšek, P and Seebens, H and Tanner, R and Touza, J and Verbrugge, L and Weber, E and Dawson, W and Kreft, H and Weigelt, P and Winter, M and Klonner, G and Talluto, MV and Dehnen-Schmutz, K}, title = {The changing role of ornamental horticulture in alien plant invasions.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1421-1437}, doi = {10.1111/brv.12402}, pmid = {29504240}, issn = {1469-185X}, abstract = {The number of alien plants escaping from cultivation into native ecosystems is increasing steadily. We provide an overview of the historical, contemporary and potential future roles of ornamental horticulture in plant invasions. We show that currently at least 75% and 93% of the global naturalised alien flora is grown in domestic and botanical gardens, respectively. Species grown in gardens also have a larger naturalised range than those that are not. After the Middle Ages, particularly in the 18th and 19th centuries, a global trade network in plants emerged. Since then, cultivated alien species also started to appear in the wild more frequently than non-cultivated aliens globally, particularly during the 19th century. Horticulture still plays a prominent role in current plant introduction, and the monetary value of live-plant imports in different parts of the world is steadily increasing. Historically, botanical gardens - an important component of horticulture - played a major role in displaying, cultivating and distributing new plant discoveries. While the role of botanical gardens in the horticultural supply chain has declined, they are still a significant link, with one-third of institutions involved in retail-plant sales and horticultural research. However, botanical gardens have also become more dependent on commercial nurseries as plant sources, particularly in North America. Plants selected for ornamental purposes are not a random selection of the global flora, and some of the plant characteristics promoted through horticulture, such as fast growth, also promote invasion. Efforts to breed non-invasive plant cultivars are still rare. Socio-economical, technological, and environmental changes will lead to novel patterns of plant introductions and invasion opportunities for the species that are already cultivated. We describe the role that horticulture could play in mediating these changes. We identify current research challenges, and call for more research efforts on the past and current role of horticulture in plant invasions. This is required to develop science-based regulatory frameworks to prevent further plant invasions.}, } @article {pmid29504232, year = {2018}, author = {Sanchez, E and Küpfer, E and Goedbloed, DJ and Nolte, AW and Lüddecke, T and Schulz, S and Vences, M and Steinfartz, S}, title = {Morphological and transcriptomic analyses reveal three discrete primary stages of postembryonic development in the common fire salamander, Salamandra salamandra.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {2}, pages = {96-108}, doi = {10.1002/jez.b.22792}, pmid = {29504232}, issn = {1552-5015}, mesh = {Alkaloids/metabolism ; Animals ; Gene Expression Profiling/*veterinary ; Gene Expression Regulation, Developmental ; Larva/genetics/growth & development ; Urodela/*genetics/*growth & development ; }, abstract = {The postembryonic development of amphibians has been characterized as divided into three predominant periods, hereafter named primary developmental stages: premetamorphosis (PreM), prometamorphosis (ProM), metamorphic climax (Meta), and completion of metamorphosis (PostM), largely based on examination of anuran development. Here, we categorized the postembryonic development of larvae of a poisonous fire salamander (Salamandra salamandra) by integrating morphology and gene expression (transcriptomic) data. Morphological analysis revealed three distinct clusters suggestive of PreM, ProM, and Meta, which were confirmed in parallel by microarray-derived gene expression analysis. In total, 3,510 probes targeted transcripts differentially expressed between the clusters we identified. Genes upregulated in PreM related to organogenesis, and those upregulated in Meta underlie structural proteins and related to development of anatomical structures and pigmentation. Biosynthesis pathways of pigments (pteridines and melanin) were upregulated during late ProM and Meta. Gas chromatographic analysis of alkaloids indicated the onset of steroidal alkaloid biosynthesis at ProM. When comparing gene expression in the fire salamander to that in other amphibians-three anurans, Xenopus laevis, X. tropicalis, and Michrohyla fissipes, and one caudate, Ambystoma mexicanum- we identified genes with conserved expression patterns involved in basic metamorphic processes such as skin restructuring and tail fin resorption. Our results support that primary stages of postembryonic development in caudates are homologous to those of anurans, and offer a baseline for the study of the evolution of developmental modes.}, } @article {pmid29504224, year = {2018}, author = {Zimova, M and Hackländer, K and Good, JM and Melo-Ferreira, J and Alves, PC and Mills, LS}, title = {Function and underlying mechanisms of seasonal colour moulting in mammals and birds: what keeps them changing in a warming world?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1478-1498}, doi = {10.1111/brv.12405}, pmid = {29504224}, issn = {1469-185X}, abstract = {Animals that occupy temperate and polar regions have specialized traits that help them survive in harsh, highly seasonal environments. One particularly important adaptation is seasonal coat colour (SCC) moulting. Over 20 species of birds and mammals distributed across the northern hemisphere undergo complete, biannual colour change from brown in the summer to completely white in the winter. But as climate change decreases duration of snow cover, seasonally winter white species (including the snowshoe hare Lepus americanus, Arctic fox Vulpes lagopus and willow ptarmigan Lagopus lagopus) become highly contrasted against dark snowless backgrounds. The negative consequences of camouflage mismatch and adaptive potential is of high interest for conservation. Here we provide the first comprehensive review across birds and mammals of the adaptive value and mechanisms underpinning SCC moulting. We found that across species, the main function of SCC moults is seasonal camouflage against snow, and photoperiod is the main driver of the moult phenology. Next, although many underlying mechanisms remain unclear, mammalian species share similarities in some aspects of hair growth, neuroendocrine control, and the effects of intrinsic and extrinsic factors on moult phenology. The underlying basis of SCC moults in birds is less understood and differs from mammals in several aspects. Lastly, our synthesis suggests that due to limited plasticity in SCC moulting, evolutionary adaptation will be necessary to mediate future camouflage mismatch and a detailed understanding of the SCC moulting will be needed to manage populations effectively under climate change.}, } @article {pmid29503459, year = {2018}, author = {Wrighton, KH}, title = {Bacterial physiology: Bridging the gap for lipopolysaccharides.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {184-185}, pmid = {29503459}, issn = {1740-1534}, } @article {pmid29503458, year = {2018}, author = {York, A}, title = {Resurrection of a poxvirus causes alarm.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {184}, doi = {10.1038/nrmicro.2018.31}, pmid = {29503458}, issn = {1740-1534}, } @article {pmid29503457, year = {2018}, author = {Kerfeld, CA and Aussignargues, C and Zarzycki, J and Cai, F and Sutter, M}, title = {Bacterial microcompartments.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {277-290}, pmid = {29503457}, issn = {1740-1534}, support = {R01 AI114975/AI/NIAID NIH HHS/United States ; }, abstract = {Bacterial microcompartments (BMCs) are self-assembling organelles that consist of an enzymatic core that is encapsulated by a selectively permeable protein shell. The potential to form BMCs is widespread and found across the kingdom Bacteria. BMCs have crucial roles in carbon dioxide fixation in autotrophs and the catabolism of organic substrates in heterotrophs. They contribute to the metabolic versatility of bacteria, providing a competitive advantage in specific environmental niches. Although BMCs were first visualized more than 60 years ago, it is mainly in the past decade that progress has been made in understanding their metabolic diversity and the structural basis of their assembly and function. This progress has not only heightened our understanding of their role in microbial metabolism but is also beginning to enable their use in a variety of applications in synthetic biology. In this Review, we focus on recent insights into the structure, assembly, diversity and function of BMCs.}, } @article {pmid29503456, year = {2018}, author = {Koch, L}, title = {Comparative genomics: Blood, guts and vampire bats.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {189}, pmid = {29503456}, issn = {1471-0064}, } @article {pmid29502873, year = {2018}, author = {Teplitski, M and de Moraes, M}, title = {Of Mice and Men....and Plants: Comparative Genomics of the Dual Lifestyles of Enteric Pathogens.}, journal = {Trends in microbiology}, volume = {26}, number = {9}, pages = {748-754}, doi = {10.1016/j.tim.2018.02.008}, pmid = {29502873}, issn = {1878-4380}, abstract = {Outbreaks of gastrointestinal illness, linked to the consumption of fruits, vegetables, and sprouts, continue to capture the attention of the general public and scientists. The recurrence of these outbreaks, despite heightened producer and consumer awareness, combined with improved sanitation protocols and technology, can be explained by the hypothesis that enteric pathogens, such as nontyphoidal Salmonella spp. and enterovirulent Escherichia coli, have evolved to exploit plants as alternative hosts. This review explores the genetic and genomic context for this hypothesis. Even though gastroenteritis outbreaks associated with the consumption of produce have been caused by a limited number of strains or serovars, robust evidence in support of the polymorphism hypothesis is lacking. While some housekeeping genes with additional virulence functions in animal models contribute to the fitness of enterics within plants, canonical virulence determinants required for animal infections, such as the type III secretion system (T3SS) and effectors, by and large, are of little consequence in interactions with plants. Conversely, despite possessing some functions more commonly found in phytobacteria, human enteric pathogens do not appear to rely on the same strategies for plant colonization. Instead, it is likely that nontyphoidal Salmonella and enterovirulent E. coli have evolved a set of functions distinct from its virulence regulon and from those used by phytopathogens.}, } @article {pmid29502298, year = {2018}, author = {Glinsky, GV}, title = {Correction to: Contribution of transposable elements and distal enhancers to evolution of human-specific features of interphase chromatin architecture in embryonic stem cells.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {1-2}, pages = {85-92}, doi = {10.1007/s10577-018-9574-3}, pmid = {29502298}, issn = {1573-6849}, abstract = {The original version of this article unfortunately contained a mistake in publishing the panel C for Figures 3, 5 and 6.}, } @article {pmid29502283, year = {2018}, author = {Whicher, A and Camprubi, E and Pinna, S and Herschy, B and Lane, N}, title = {Acetyl Phosphate as a Primordial Energy Currency at the Origin of Life.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {2}, pages = {159-179}, pmid = {29502283}, issn = {1573-0875}, support = {RPG-425//Leverhulme Trust/ ; }, mesh = {*Hot Temperature ; Hydrogen-Ion Concentration ; Hydrothermal Vents ; Organophosphates/chemical synthesis/*chemistry ; *Origin of Life ; Water/*chemistry ; }, abstract = {Metabolism is primed through the formation of thioesters via acetyl CoA and the phosphorylation of substrates by ATP. Prebiotic equivalents such as methyl thioacetate and acetyl phosphate have been proposed to catalyse analogous reactions at the origin of life, but their propensity to hydrolyse challenges this view. Here we show that acetyl phosphate (AcP) can be synthesised in water within minutes from thioacetate (but not methyl thioacetate) under ambient conditions. AcP is stable over hours, depending on temperature, pH and cation content, giving it an ideal poise between stability and reactivity. We show that AcP can phosphorylate nucleotide precursors such as ribose to ribose-5-phosphate and adenosine to adenosine monophosphate, at modest (~2%) yield in water, and at a range of pH. AcP can also phosphorylate ADP to ATP in water over several hours at 50 °C. But AcP did not promote polymerization of either glycine or AMP. The amino group of glycine was preferentially acetylated by AcP, especially at alkaline pH, hindering the formation of polypeptides. AMP formed small stacks of up to 7 monomers, but these did not polymerise in the presence of AcP in aqueous solution. We conclude that AcP can phosphorylate biologically meaningful substrates in a manner analogous to ATP, promoting the origins of metabolism, but is unlikely to have driven polymerization of macromolecules such as polypeptides or RNA in free solution. This is consistent with the idea that a period of monomer (cofactor) catalysis preceded the emergence of polymeric enzymes or ribozymes at the origin of life.}, } @article {pmid29502185, year = {2018}, author = {Yang, D and Liang, S and Yang, Q and Liu, D and Qin, Z and Zhang, Z}, title = {Expression characteristics and functional analysis of Krüppel-like factor 4 in adductor muscle and mantle of Zhikong scallop Chlamys farreri.}, journal = {Development genes and evolution}, volume = {228}, number = {2}, pages = {95-103}, pmid = {29502185}, issn = {1432-041X}, support = {31602139//National Natural Science Foundation of China/International ; 2012AA10A402//National High Technology Research and Development Program of China/International ; }, mesh = {Animal Shells/growth & development/*metabolism ; Animals ; *Gene Expression Regulation ; Kruppel-Like Transcription Factors/genetics/*metabolism ; Muscle, Skeletal/growth & development/metabolism ; Pectinidae/genetics/growth & development/*metabolism ; }, abstract = {Krüppel-like factor 4 (KLF4) is an important transcription factor involving in formation and maintenance of muscles in mammals. However, no data are available on KLF4 function in shellfish muscles which play vital roles in the movement, stress response, and physiology in shellfish. In the present study, we revealed that the Klf4 mRNA of Zhikong scallop Chlamys farreri was expressed in most tissues, which has high level in adductor muscle, mantle, kidney, and testis. Positive signals of the Klf4 mRNA and protein were visible in all skeletal muscle fibers of adductor muscle, and all the cells of C. farreri mantle. Furthermore, the knockdown of Klf4 mRNA in adductor muscle and mantle by means of in vivo RNA interference led to some different phenotypes, including disordered arrangement of muscle fibers in adductor muscle and mantle, abnormal structures of skeletal muscles, and reduced muscle fibers under endepidermis of mantle. Our findings demonstrated that Klf4 plays important roles in maintenance of muscle functions in C. farreri adductor muscle and mantle, and suggested that its regulatory way in skeletal muscle may be different from the smooth muscle in shellfish.}, } @article {pmid29501785, year = {2018}, author = {Surveswaran, S and Gowda, V and Sun, M}, title = {Using an integrated approach to identify cryptic species, divergence patterns and hybrid species in Asian ladies' tresses orchids (Spiranthes, Orchidaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {106-121}, doi = {10.1016/j.ympev.2018.02.025}, pmid = {29501785}, issn = {1095-9513}, mesh = {*Biological Evolution ; DNA, Chloroplast/genetics ; DNA, Ribosomal Spacer/genetics ; *Genetic Variation ; *Hybridization, Genetic ; Likelihood Functions ; Orchidaceae/*genetics ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Species Specificity ; Time Factors ; }, abstract = {Spiranthes (∼36 species, Orchidaceae) is a small genus with a global distribution. It has a center of diversity in North America with only a few species occurring in Asia. This study focuses on the Asian Spiranthes with an emphasis on understanding their biogeographic relationships and species delimitations using molecular markers. Our phylogenetic trees based on nuclear (ITS) and chloroplast (trnL-trnLF, matK and trnS-G) sequences from samples across their range in Asia revealed the Asian Spiranthes are monophyletic. Ancestral area optimization suggested that North America forms the ancestral region for the Asian Spiranthes rather than Europe suggesting that they originated from a single long-distance dispersal event. Our study also revealed the presence of a cryptic species S. himalayensis, which was discovered based on molecular data thus emphasizing the importance of wide geographical sampling in phylogenetic studies. Sequences of cloned ITS provided support for the hypothesis that natural hybridization between S. sinensis and the newly described S. himalayensis resulted in the allotetraploid S. hongkongensis, with S. himalayensis as the paternal parent. One of the species complexes known in Asia is the S. sinensis complex, which shows a wide occurrence and is known for local geographical variants. Some of these variants have been described as new species in Australia and New Zealand. Our studies show that all the sampled variants including the Australian and New Zealand species show monophyly despite having long branches. This suggests that there may be high rates of gene flow between the geographically distinct forms resulting in lack of species resolution within the S. sinensis complex.}, } @article {pmid29501479, year = {2018}, author = {Daims, H and Wagner, M}, title = {Nitrospira.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {462-463}, doi = {10.1016/j.tim.2018.02.001}, pmid = {29501479}, issn = {1878-4380}, mesh = {Ammonia/metabolism ; Archaea/metabolism ; Bacteria/classification/*metabolism ; Ecosystem ; Environmental Microbiology ; Formates/metabolism ; Nitrates/metabolism ; *Nitrification ; Nitrites/metabolism ; Oxidation-Reduction ; Oxygen ; }, abstract = {In this infographic, the key metabolic functions of Nitrospira and the role that these bacteria play in nitrification and other processes in the environment is shown. Nitrospira plays pivotal roles in nitrification as an aerobic chemolithoautotrophic nitrite-oxidizing bacterium. These bacteria often occur in close association with ammonia-oxidizing bacteria or archaea that convert ammonia to nitrite, which is further oxidized to nitrate by Nitrospira. However, in 'reciprocal feeding' interactions, Nitrospira can also provide ammonia oxidizers with ammonia released from urea or cyanate, which is further nitrified as described above. Recently discovered Nitrospira members even catalyze both nitrification steps alone and are therefore called complete ammonia oxidizers or 'comammox' organisms. Some strains of Nitrospira utilize alternative substrates, such as H2 and formate, using oxygen or nitrate as terminal electron acceptor, and can exploit these energy sources concurrently with aerobic nitrite oxidation. This metabolic versatility enables Nitrospira to colonize a broad range of habitats and to sustain shifts in environmental conditions such as changing oxygen concentrations.}, } @article {pmid29501478, year = {2018}, author = {Teitzel, G}, title = {25 Years of Trends in Microbiology: Window to the Past and Future.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {243-245}, doi = {10.1016/j.tim.2018.02.005}, pmid = {29501478}, issn = {1878-4380}, } @article {pmid29501457, year = {2018}, author = {Genuth, MA and Allen, CDC and Mikawa, T and Weiner, OD}, title = {Chick cranial neural crest cells use progressive polarity refinement, not contact inhibition of locomotion, to guide their migration.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29501457}, issn = {1095-564X}, support = {T32 GM007810/GM/NIGMS NIH HHS/United States ; R01 HL132832/HL/NHLBI NIH HHS/United States ; R37 HL078921/HL/NHLBI NIH HHS/United States ; R01 HL122375/HL/NHLBI NIH HHS/United States ; R35 GM118167/GM/NIGMS NIH HHS/United States ; }, abstract = {To move directionally, cells can bias the generation of protrusions or select among randomly generated protrusions. Here we use 3D two-photon imaging of chick branchial arch 2 directed neural crest cells to probe how these mechanisms contribute to directed movement, whether a subset or the majority of cells polarize during movement, and how the different classes of protrusions relate to one another. We find that, in contrast to Xenopus, cells throughout the stream are morphologically polarized along the direction of overall stream movement and do not exhibit contact inhibition of locomotion. Instead chick neural crest cells display a progressive sharpening of the morphological polarity program. Neural crest cells have weak spatial biases in filopodia generation and lifetime. Local bursts of filopodial generation precede the generation of larger protrusions. These larger protrusions are more spatially biased than the filopodia, and the subset of protrusions that are productive for motility are the most polarized of all. Orientation rather than position is the best correlate of the protrusions that are selected for cell guidance. This progressive polarity refinement strategy may enable neural crest cells to efficiently explore their environment and migrate accurately in the face of noisy guidance cues.}, } @article {pmid29501375, year = {2018}, author = {Taheri, S and James, S and Roy, V and Decaëns, T and Williams, BW and Anderson, F and Rougerie, R and Chang, CH and Brown, G and Cunha, L and Stanton, DWG and Da Silva, E and Chen, JH and Lemmon, AR and Moriarty Lemmon, E and Bartz, M and Baretta, D and Barois, I and Lapied, E and Coulis, M and Dupont, L}, title = {Complex taxonomy of the 'brush tail' peregrine earthworm Pontoscolex corethrurus.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {60-70}, doi = {10.1016/j.ympev.2018.02.021}, pmid = {29501375}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Genetic Markers ; Geography ; Haplotypes/genetics ; Oligochaeta/anatomy & histology/*classification ; Phylogeny ; Species Specificity ; Sympatry ; }, abstract = {Pontoscolex corethrurus is the most widespread earthworm species in tropical and sub-tropical zones and one of the most studied in soil science. Although, ecological interactions of P. corethrurus with its environment are well documented, the taxonomic status of the species remains unclear. In this study, we investigated phylogenetic relationships within the genus Pontoscolex, in particular focusing on morphologically indistinguishable (i.e., cryptic) lineages. A total of 792 specimens collected from 25 different countries and islands all over the world were analyzed using two mitochondrial (COI and 16S rDNA) and two nuclear (internal transcribed spacers 2 and 28S rDNA) markers, and a total of 11 morphological characters both internal and external were investigated in all genetically characterized lineages. A large-scale multilocus sequence data matrix was also obtained for Pontoscolex spp. specimens using the Anchored Hybrid Enrichment (AHE) method. Multilocus phylogenetic and phylogenomic analyses, combined with species delimitation methods; including single locus (mPTP, ABGD) and multilocus (BPP) approaches, revealed congruent results. Four cryptic species were supported within the P. corethrurus species complex, and four potentially new species within the genus Pontoscolex. One widespread lineage (L1), within P. corethrurus complex was observed in the current population of Fritz Müller's garden where P. corethrurus was first described in 1856. Cryptic lineages were observed in sympatry at several localities. This, in combination with observed heteroplasmy in COI gene in one population raises an important question of reproductive isolation between these species.}, } @article {pmid29501374, year = {2018}, author = {Everson, KM and Hildebrandt, KBP and Goodman, SM and Olson, LE}, title = {Caught in the act: Incipient speciation across a latitudinal gradient in a semifossorial mammal from Madagascar, the mole tenrec Oryzorictes hova (Tenrecidae).}, journal = {Molecular phylogenetics and evolution}, volume = {126}, number = {}, pages = {74-84}, doi = {10.1016/j.ympev.2018.02.024}, pmid = {29501374}, issn = {1095-9513}, mesh = {*Altitude ; Animals ; Bayes Theorem ; Biodiversity ; *Genetic Speciation ; Genetics, Population ; Haplotypes/genetics ; Madagascar ; Mammals/*genetics ; Phylogeny ; Phylogeography ; Principal Component Analysis ; Species Specificity ; Time Factors ; }, abstract = {Madagascar is one of the world's foremost biodiversity hotspots, yet a large portion of its flora and fauna remains undescribed and the driving forces of in situ diversification are not well understood. Recent studies have identified a widespread, latitudinally structured phylogeographic pattern in Madagascar's humid-forest mammals, amphibians, reptiles, and insects. Several factors may be driving this pattern, namely biogeographic barriers (i.e., rivers or valleys) or past episodes of forest contraction and expansion. In this study, we describe the phylogeographic structure of the small, semifossorial mammal Oryzorictes hova, one of Madagascar's two species of mole tenrec, found throughout Madagascar's eastern humid forest belt, from high-elevation montane forest to low-elevation forests, as well as disturbed habitat such as rice fields. Using one mitochondrial locus, four nuclear loci, and 31 craniomandibular measurements, we identified three distinct populations of O. hova associated with the northern, central, and southern regions of the island. We found little evidence of gene flow among these populations, so we treated each population as a potential species. We validated species limits using two Bayesian methods: BP&P, employing only DNA sequence data, and iBPP using both DNA and morphological data, and we assessed whether these methods are susceptible to producing false positive errors. Molecular and morphological data support the recognition of each of the three populations of O. hova as distinct species, but formal species descriptions will require additional data from type specimens. This study illustrates the importance of using integrative datasets, multiple methodological approaches, and extensive geographic sampling for species delimitation and adds evidence for a widespread phylogeographic pattern in Madagascar's humid forest taxa.}, } @article {pmid29501373, year = {2018}, author = {Horká, I and De Grave, S and Fransen, CHJM and Petrusek, A and Ďuriš, Z}, title = {Multiple origins and strong phenotypic convergence in fish-cleaning palaemonid shrimp lineages.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {71-81}, doi = {10.1016/j.ympev.2018.02.006}, pmid = {29501373}, issn = {1095-9513}, mesh = {Acclimatization ; Animals ; Bayes Theorem ; Behavior, Animal ; Likelihood Functions ; Palaemonidae/*physiology ; Perciformes/*physiology ; Phenotype ; *Phylogeny ; Pigmentation ; *Symbiosis ; }, abstract = {Several species of palaemonid shrimps are known to act as fish-cleaning symbionts, with cleaning interactions ranging from dedicated (obligate) to facultative. We confirmed five evolutionarily independent origins of fish cleaning symbioses within the family Palaemonidae based on a phylogenetic analysis and the ancestral state reconstruction of 68 species, including 13 fish-cleaners from the genera Ancylomenes, Brachycarpus, Palaemon, Periclimenes, and Urocaridella. We focus in particular on two distantly related lineages of fish cleaning shrimps with allopatric distributions, the Indo-West Pacific Ancylomenes and the western Atlantic monophyletic Ancylomenes/Periclimenes group, which exhibit striking similarities in morphology, colouration and complex behaviour. Specifically, representatives of both lineages are similar in: (1) the general body shape and colour pattern; (2) the utilization of sea anemones as conspicuous cleaning stations; and (3) the use of sideways body swaying to visually promote their bright colour spots in order to attract fish clients. Such morphological, ecological and ethological convergences are apparently due to adaptations to fish cleaning linked to the establishment of similar modes of communication with fish clients in these species.}, } @article {pmid29500185, year = {2018}, author = {Wu, W and Liu, F and Singh, S}, title = {Toward engineering E. coli with an autoregulatory system for lignin valorization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2970-2975}, pmid = {29500185}, issn = {1091-6490}, mesh = {Benzaldehydes/pharmacology ; *Biomass ; Carrier Proteins ; Catechols/pharmacology ; Escherichia coli/drug effects/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; Lignin/*metabolism ; Metabolic Networks and Pathways/*physiology ; Rhodopseudomonas/metabolism ; Vanillic Acid/pharmacology ; }, abstract = {Efficient lignin valorization could add more than 10-fold the value gained from burning it for energy and is critical for economic viability of future biorefineries. However, lignin-derived aromatics from biomass pretreatment are known to be potent fermentation inhibitors in microbial production of fuels and other value-added chemicals. In addition, isopropyl-β-d-1-thiogalactopyranoside and other inducers are routinely added into fermentation broth to induce the expression of pathway enzymes, which further adds to the overall process cost. An autoregulatory system that can diminish the aromatics' toxicity as well as be substrate-inducible can be the key for successful integration of lignin valorization into future lignocellulosic biorefineries. Toward that goal, in this study an autoregulatory system is demonstrated that alleviates the toxicity issue and eliminates the cost of an external inducer. Specifically, this system is composed of a catechol biosynthesis pathway coexpressed with an active aromatic transporter CouP under induction by a vanillin self-inducible promoter, ADH7, to effectively convert the lignin-derived aromatics into value-added chemicals using Escherichia coli as a host. The constructed autoregulatory system can efficiently transport vanillin across the cell membrane and convert it to catechol. Compared with the system without CouP expression, the expression of catechol biosynthesis pathway with transporter CouP significantly improved the catechol yields about 30% and 40% under promoter pTrc and ADH7, respectively. This study demonstrated an aromatic-induced autoregulatory system that enabled conversion of lignin-derived aromatics into catechol without the addition of any costly, external inducers, providing a promising and economically viable route for lignin valorization.}, } @article {pmid29500037, year = {2018}, author = {Shih, C and Yang, CC and Choijilsuren, G and Chang, CH and Liou, AT}, title = {Hepatitis B Virus.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {386-387}, doi = {10.1016/j.tim.2018.01.009}, pmid = {29500037}, issn = {1878-4380}, abstract = {This infographic about hepatitis B virus explores its replication cycle, natural history of infection and pathogenesis, and how this can be controlled and treated. Hepatitis B virus (HBV) is a common worldwide blood-borne pathogen. Chronic hepatitis B can progress to an inactive carrier state, and then, in some patients, give rise to cirrhosis and cancer of the liver, leading to death. An HBV surface-antigen vaccine is effective, but treatments are currently not curative. HBV replicates via reverse transcription. Its covalently closed circular (ccc) DNA in the nucleus encodes a pregenomic RNA (pgRNA), which can be encapsidated by HBV polymerase. Reverse transcription occurs in the capsids by using the pgRNA as a template for the synthesis of single-stranded linear and then partially double-stranded relaxed circular (rc) DNA. Capsids containing a mature rc DNA genome target to the nucleus for ccc DNA synthesis. Persistent HBV infection is caused mainly by ccc DNA and immune tolerance to HBV antigens in the liver. Unlike acute infection, chronic carriers contain only a low level of HBV core-antigen-specific T cell activity, contributing to the lack of viral clearance.}, } @article {pmid29500036, year = {2018}, author = {}, title = {How Has Microbiology Changed over the Past 25 Years?.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {246-250}, doi = {10.1016/j.tim.2018.02.002}, pmid = {29500036}, issn = {1878-4380}, } @article {pmid29500034, year = {2018}, author = {Fernandes, JN and Moise, IK and Maranto, GL and Beier, JC}, title = {Revamping Mosquito-borne Disease Control to Tackle Future Threats.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {359-368}, doi = {10.1016/j.pt.2018.01.005}, pmid = {29500034}, issn = {1471-5007}, support = {R01 AI100968/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chikungunya Fever/epidemiology/*prevention & control ; Dengue/epidemiology/*prevention & control ; Disease Outbreaks/*prevention & control ; Humans ; Mosquito Control/*statistics & numerical data ; *Mosquito Vectors ; Zika Virus Infection/epidemiology/*prevention & control ; }, abstract = {The global approach to mosquito-borne diseases (MBDs) is in need of critical re-evaluation. Although there have been dramatic reductions in malaria incidence since 2000, malaria elimination from high-transmission settings remains problematic. At the same time, arbovirus outbreaks have increased in their frequency and impact. The 2015-2016 Zika virus epidemic exposed the dire state of MBD control in many countries, calling for united global action. Despite international resolve to prevent future epidemics, current practices in MBD control are mostly reactive and of limited efficacy. In this Opinion article, we summarize the views of 25 international mosquito experts about the current state of MBD control and highlight the issues that must be addressed in order to tackle emerging threats on the horizon.}, } @article {pmid29500033, year = {2018}, author = {Booth, M and Clements, A}, title = {Neglected Tropical Disease Control - The Case for Adaptive, Location-specific Solutions.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {272-282}, doi = {10.1016/j.pt.2018.02.001}, pmid = {29500033}, issn = {1471-5007}, mesh = {Animals ; Climate Change ; Humans ; Neglected Diseases/*prevention & control ; Tropical Medicine/standards/*trends ; }, abstract = {The world is experiencing environmental and social change at an unprecedented rate, with the effects being felt at local, regional, and international scales. This phenomenon may disrupt interventions against neglected tropical diseases (NTDs) that operate on the basis of linear scaling and 'one-size-fits-all'. Here we argue that investment in field-based data collection and building modelling capacity is required; that it is important to consider unintended consequences of interventions; that inferences can be drawn from wildlife ecology; and that interventions should become more location-specific. Collectively, these ideas underpin the development of adaptive decision-support tools that are sufficiently flexible to address emerging issues within the Anthropocene.}, } @article {pmid29499907, year = {2018}, author = {Bravo Núñez, MA and Nuckolls, NL and Zanders, SE}, title = {Genetic Villains: Killer Meiotic Drivers.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {6}, pages = {424-433}, pmid = {29499907}, issn = {0168-9525}, support = {R00 GM114436/GM/NIGMS NIH HHS/United States ; }, abstract = {Unbiased allele transmission into progeny is a fundamental genetic concept canonized as Mendel's Law of Segregation. Not all alleles, however, abide by the law. Killer meiotic drivers are ultra-selfish DNA sequences that are transmitted into more than half (sometimes all) of the meiotic products generated by a heterozygote. As their name implies, these loci gain a transmission advantage in heterozygotes by destroying otherwise viable meiotic products that do not inherit the driver. We review and classify killer meiotic drive genes across a wide spectrum of eukaryotes. We discuss how analyses of these ultra-selfish genes can lead to greater insight into the mechanisms of gametogenesis and the causes of infertility.}, } @article {pmid29499759, year = {2018}, author = {Eng, A and Borenstein, E}, title = {Taxa-function robustness in microbial communities.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {45}, pmid = {29499759}, issn = {2049-2618}, support = {DP2 AT007802/AT/NCCIH NIH HHS/United States ; DP2 AT007802-01//National Institutes of Health (US)/International ; }, mesh = {Bacteria/*classification/*genetics ; Biodiversity ; Cellular Microenvironment/*physiology ; Computer Simulation ; Environment ; Female ; Gastrointestinal Tract/microbiology ; Humans ; Metagenomics ; Microbiota/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Vagina/microbiology ; }, abstract = {BACKGROUND: The species composition of a microbial community is rarely fixed and often experiences fluctuations of varying degrees and at varying frequencies. These perturbations to a community's taxonomic profile naturally also alter the community's functional profile-the aggregate set of genes encoded by community members-ultimately altering the community's overall functional capacities. The magnitude of such functional changes and the specific shift that will occur in each function, however, are strongly dependent on how genes are distributed across community members' genomes. This gene distribution, in turn, is determined by the taxonomic composition of the community and would markedly differ, for example, between communities composed of species with similar genomic content vs. communities composed of species whose genomes encode relatively distinct gene sets. Combined, these observations suggest that community functional robustness to taxonomic perturbations could vary widely across communities with different compositions, yet, to date, a systematic study of the inherent link between community composition and robustness is lacking.

RESULTS: In this study, we examined how a community's taxonomic composition influences the robustness of that community's functional profile to taxonomic perturbation (here termed taxa-function robustness) across a wide array of environments. Using a novel simulation-based computational model to quantify this taxa-function robustness in host-associated and non-host-associated communities, we find notable differences in robustness between communities inhabiting different body sites, including significantly higher robustness in gut communities compared to vaginal communities that cannot be attributed solely to differences in species richness. We additionally find between-site differences in the robustness of specific functions, some of which are potentially related to site-specific environmental conditions. These taxa-function robustness differences are most strongly associated with differences in overall functional redundancy, though other aspects of gene distribution also influence taxa-function robustness in certain body environments, and are sufficient to cluster communities by environment. Further analysis revealed a correspondence between our robustness estimates and taxonomic and functional shifts observed across human-associated communities.

CONCLUSIONS: Our analysis approach revealed intriguing taxa-function robustness variation across environments and identified features of community and gene distribution that impact robustness. This approach could be further applied for estimating taxa-function robustness in novel communities and for informing the design of synthetic communities with specific robustness requirements.}, } @article {pmid29499753, year = {2018}, author = {Langenfeld, A and Bastiaenen, C and Brunner, F and Swanenburg, J}, title = {Validation of the Orebro musculoskeletal pain screening questionnaire in patients with chronic neck pain.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {161}, pmid = {29499753}, issn = {1756-0500}, mesh = {Adult ; Female ; Humans ; Male ; Middle Aged ; Musculoskeletal Pain/*diagnosis ; Neck Pain/*diagnosis ; Pain Measurement/*standards ; Reproducibility of Results ; Surveys and Questionnaires/standards ; }, abstract = {OBJECTIVES: To validate the German version of OMPSQ (OMPSQ-G) for patients with chronic neck pain.

RESULTS: After translating OMPSQ to German, we assessed the discriminant validity between patients and healthy adults. Convergent validity was assessed using Pearson's correlation coefficients between domains of OMPSQ-G and the German version of neck disability index (NDI-G) and visual analogue scale (VAS) of neck pain intensity. Floor and ceiling effects, internal consistency, test-retest and relative reliability were assessed. Fifty patients with chronic neck pain (mean age, 43.6 years; 34 females) and 24 healthy adults (mean age, 50.4 years; 18 females) participated. Mann-Whitney U tests showed significant differences in OMPSQ scores between both groups at the baseline (z = - 4.6; p < 0.001) and second time point (z = - 4.8; p < 0.001). OMPSQ-G scores highly and moderately correlated with NDI-G (ρ = 0.70) and VAS (ρ = 0.41) scores, respectively. There were no floor or ceiling effects. Cronbach's alpha was 0.94. OMPSQ-G showed high reliability (intraclass correlation 2.1: 0.93; standard error of measurement, 6.9; smallest detectable change, 20 points). The Bland-Altman plot indicated no systematic error. OMPSQ-G showed good validity and reliability in patients with neck pain. Trial registration NCT02540343.}, } @article {pmid29499736, year = {2018}, author = {Assefa, L and Alemayehu, M and Debie, A}, title = {Magnitude of institutional delivery service utilization and associated factors among women in pastoral community of Awash Fentale district Afar Regional State, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {162}, pmid = {29499736}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Delivery, Obstetric/*statistics & numerical data ; Ethiopia ; Female ; Health Services Accessibility/*statistics & numerical data ; Humans ; Maternal Health Services/*statistics & numerical data ; Middle Aged ; Rural Population/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: Reduction of maternal mortality is a global priority particularly in developing countries like Ethiopia where maternal mortality ratio is one of the highest in the world. Most deliveries in developing countries occur at home without skilled birth attendants. Therefore, the objective of this study was to assess institutional delivery service utilization and associated factors among women in pastoral community of Awash Fentale district, Ethiopia.

RESULTS: Overall, 35.2% of women delivered at health facilities. Women who had good knowledge AOR = 2.1, 95% CI 1.32, 4.87), Ante Natal Care (ANC) follow up (AOR = 3.2, 95% CI 1.55, 6.63), resided in a place where distance to reach at the nearby health facilities takes < 30 min (AOR = 3.1; 95% CI 2.57, 66.33) and women whose husband involved in decision regarding delivery place (AOR = 1.9; 95% CI 1.49, 5.07) were more likely to deliver at health facility. Therefore, strengthening ANC services, improving maternal knowledge, involving husbands in decision of delivery place and expanding health facilities in the community would enhance institutional delivery.}, } @article {pmid29499717, year = {2018}, author = {Opulente, DA and Rollinson, EJ and Bernick-Roehr, C and Hulfachor, AB and Rokas, A and Kurtzman, CP and Hittinger, CT}, title = {Factors driving metabolic diversity in the budding yeast subphylum.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {26}, pmid = {29499717}, issn = {1741-7007}, support = {DEB-1442113//Directorate for Biological Sciences/International ; DEB-1442148//Directorate for Biological Sciences/International ; Hatch Project 1003258//National Institute of Food and Agriculture/International ; BER DE-FC02-07ER64494 and DE-SC0018409//DOE Great Lakes Bioenergy Research Center/International ; Pew Scholar in the Biomedical Sciences//Pew Charitable Trusts/International ; Vilas Faculty Early Career Investigator//Vilas Trust Fund/International ; }, abstract = {BACKGROUND: Associations between traits are prevalent in nature, occurring across a diverse range of taxa and traits. Individual traits may co-evolve with one other, and these correlations can be driven by factors intrinsic or extrinsic to an organism. However, few studies, especially in microbes, have simultaneously investigated both across a broad taxonomic range. Here we quantify pairwise associations among 48 traits across 784 diverse yeast species of the ancient budding yeast subphylum Saccharomycotina, assessing the effects of phylogenetic history, genetics, and ecology.

RESULTS: We find extensive negative (traits that tend to not occur together) and positive (traits that tend to co-occur) pairwise associations among traits, as well as between traits and environments. These associations can largely be explained by the biological properties of the traits, such as overlapping biochemical pathways. The isolation environments of the yeasts explain a minor but significant component of the variance, while phylogeny (the retention of ancestral traits in descendant species) plays an even more limited role. Positive correlations are pervasive among carbon utilization traits and track with chemical structures (e.g., glucosides and sugar alcohols) and metabolic pathways, suggesting a molecular basis for the presence of suites of traits. In several cases, characterized genes from model organisms suggest that enzyme promiscuity and overlapping biochemical pathways are likely mechanisms to explain these macroevolutionary trends. Interestingly, fermentation traits are negatively correlated with the utilization of pentose sugars, which are major components of the plant biomass degraded by fungi and present major bottlenecks to the production of cellulosic biofuels. Finally, we show that mammalian pathogenic and commensal yeasts have a suite of traits that includes growth at high temperature and, surprisingly, the utilization of a narrowed panel of carbon sources.

CONCLUSIONS: These results demonstrate how both intrinsic physiological factors and extrinsic ecological factors drive the distribution of traits present in diverse organisms across macroevolutionary timescales.}, } @article {pmid29499714, year = {2018}, author = {Kavvas, ES and Seif, Y and Yurkovich, JT and Norsigian, C and Poudel, S and Greenwald, WW and Ghatak, S and Palsson, BO and Monk, JM}, title = {Updated and standardized genome-scale reconstruction of Mycobacterium tuberculosis H37Rv, iEK1011, simulates flux states indicative of physiological conditions.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {25}, pmid = {29499714}, issn = {1752-0509}, support = {U01 AI124316/AI/NIAID NIH HHS/United States ; 1-UO1-AI124316-01//National Institute of Allergy and Infectious Diseases/ ; }, abstract = {BACKGROUND: The efficacy of antibiotics against M. tuberculosis has been shown to be influenced by experimental media conditions. Investigations of M. tuberculosis growth in physiological conditions have described an environment that is different from common in vitro media. Thus, elucidating the interplay between available nutrient sources and antibiotic efficacy has clear medical relevance. While genome-scale reconstructions of M. tuberculosis have enabled the ability to interrogate media differences for the past 10 years, recent reconstructions have diverged from each other without standardization. A unified reconstruction of M. tuberculosis H37Rv would elucidate the impact of different nutrient conditions on antibiotic efficacy and provide new insights for therapeutic intervention.

RESULTS: We present a new genome-scale model of M. tuberculosis H37Rv, named iEK1011, that unifies and updates previous M. tuberculosis H37Rv genome-scale reconstructions. We functionally assess iEK1011 against previous models and show that the model increases correct gene essentiality predictions on two different experimental datasets by 6% (53% to 60%) and 18% (60% to 71%), respectively. We compared simulations between in vitro and approximated in vivo media conditions to examine the predictive capabilities of iEK1011. The simulated differences recapitulated literature defined characteristics in the rewiring of TCA metabolism including succinate secretion, gluconeogenesis, and activation of both the glyoxylate shunt and the methylcitrate cycle. To assist efforts to elucidate mechanisms of antibiotic resistance development, we curated 16 metabolic genes related to antimicrobial resistance and approximated evolutionary drivers of resistance. Comparing simulations of these antibiotic resistance features between in vivo and in vitro media highlighted condition-dependent differences that may influence the efficacy of antibiotics.

CONCLUSIONS: iEK1011 provides a computational knowledge base for exploring the impact of different environmental conditions on the metabolic state of M. tuberculosis H37Rv. As more experimental data and knowledge of M. tuberculosis H37Rv become available, a unified and standardized M. tuberculosis model will prove to be a valuable resource to the research community studying the systems biology of M. tuberculosis.}, } @article {pmid29499650, year = {2018}, author = {Zhu, BH and Xiao, J and Xue, W and Xu, GC and Sun, MY and Li, JT}, title = {P_RNA_scaffolder: a fast and accurate genome scaffolder using paired-end RNA-sequencing reads.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {175}, pmid = {29499650}, issn = {1471-2164}, support = {2014C010//Special Scientific Research Funds for Central Non-profit Institutes, Chinese Academy of Fishery Sciences/International ; 31402353//National Natural Science Foundation of China/International ; 31672644//National Natural Science Foundation of China/International ; }, mesh = {*Algorithms ; *Genome, Human ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; RNA/genetics ; Sequence Analysis, DNA/*methods ; *Software ; }, abstract = {BACKGROUND: Obtaining complete gene structures is one major goal of genome assembly. Some gene regions are fragmented in low quality and high-quality assemblies. Therefore, new approaches are needed to recover gene regions. Genomes are widely transcribed, generating messenger and non-coding RNAs. These widespread transcripts can be used to scaffold genomes and complete transcribed regions.

RESULTS: We present P_RNA_scaffolder, a fast and accurate tool using paired-end RNA-sequencing reads to scaffold genomes. This tool aims to improve the completeness of both protein-coding and non-coding genes. After this tool was applied to scaffolding human contigs, the structures of both protein-coding genes and circular RNAs were almost completely recovered and equivalent to those in a complete genome, especially for long proteins and long circular RNAs. Tested in various species, P_RNA_scaffolder exhibited higher speed and efficiency than the existing state-of-the-art scaffolders. This tool also improved the contiguity of genome assemblies generated by current mate-pair scaffolding and third-generation single-molecule sequencing assembly.

CONCLUSIONS: The P_RNA_scaffolder can improve the contiguity of genome assembly and benefit gene prediction. This tool is available at http://www.fishbrowser.org/software/P_RNA_scaffolder .}, } @article {pmid29499649, year = {2018}, author = {Hernández, Y and Bernstein, R and Pagan, P and Vargas, L and McCaig, W and Ramrattan, G and Akther, S and Larracuente, A and Di, L and Vieira, FG and Qiu, WG}, title = {BpWrapper: BioPerl-based sequence and tree utilities for rapid prototyping of bioinformatics pipelines.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {76}, pmid = {29499649}, issn = {1471-2105}, support = {AI107955//National Institute of Allergy and Infectious Diseases/International ; R25 GM060665/GM/NIGMS NIH HHS/United States ; SC1 AI107955/AI/NIAID NIH HHS/United States ; MD007599//National Center on Minority Health and Health Disparities/International ; T34 GM007823/GM/NIGMS NIH HHS/United States ; }, mesh = {Base Sequence ; Computational Biology/*methods ; *Phylogeny ; Sequence Alignment ; *Software ; }, abstract = {BACKGROUND: Automated bioinformatics workflows are more robust, easier to maintain, and results more reproducible when built with command-line utilities than with custom-coded scripts. Command-line utilities further benefit by relieving bioinformatics developers to learn the use of, or to interact directly with, biological software libraries. There is however a lack of command-line utilities that leverage popular Open Source biological software toolkits such as BioPerl (http://bioperl.org) to make many of the well-designed, robust, and routinely used biological classes available for a wider base of end users.

RESULTS: Designed as standard utilities for UNIX-family operating systems, BpWrapper makes functionality of some of the most popular BioPerl modules readily accessible on the command line to novice as well as to experienced bioinformatics practitioners. The initial release of BpWrapper includes four utilities with concise command-line user interfaces, bioseq, bioaln, biotree, and biopop, specialized for manipulation of molecular sequences, sequence alignments, phylogenetic trees, and DNA polymorphisms, respectively. Over a hundred methods are currently available as command-line options and new methods are easily incorporated. Performance of BpWrapper utilities lags that of precompiled utilities while equivalent to that of other utilities based on BioPerl. BpWrapper has been tested on BioPerl Release 1.6, Perl versions 5.10.1 to 5.25.10, and operating systems including Apple macOS, Microsoft Windows, and GNU/Linux. Release code is available from the Comprehensive Perl Archive Network (CPAN) at https://metacpan.org/pod/Bio::BPWrapper . Source code is available on GitHub at https://github.com/bioperl/p5-bpwrapper .

CONCLUSIONS: BpWrapper improves on existing sequence utilities by following the design principles of Unix text utilities such including a concise user interface, extensive command-line options, and standard input/output for serialized operations. Further, dozens of novel methods for manipulation of sequences, alignments, and phylogenetic trees, unavailable in existing utilities (e.g., EMBOSS, Newick Utilities, and FAST), are provided. Bioinformaticians should find BpWrapper useful for rapid prototyping of workflows on the command-line without creating custom scripts for comparative genomics and other bioinformatics applications.}, } @article {pmid29499648, year = {2018}, author = {Miao, L and Lv, Y and Kong, L and Chen, Q and Chen, C and Li, J and Zeng, F and Wang, S and Li, J and Huang, L and Cao, J and Yu, X}, title = {Genome-wide identification, phylogeny, evolution, and expression patterns of MtN3/saliva/SWEET genes and functional analysis of BcNS in Brassica rapa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {174}, pmid = {29499648}, issn = {1471-2164}, support = {2016YFD0100204-31//Ministry of Science and Technology of the People's Republic of China/International ; 2014-Z28//Ministry of Agriculture of the People's Republic of China/International ; 31460521//National Natural Science Foundation of China/International ; 2016C02051-6-1//Science Thchnology Department of Zhejiang Province/International ; 2014C32008//Science Thchnology Department of Zhejiang Province/International ; CX(15)1016//Science and Technology Department of Jiangsu Province/International ; }, mesh = {Brassica rapa/genetics/growth & development/*metabolism ; Chromosome Mapping/methods ; Chromosomes, Plant ; *Evolution, Molecular ; Flowers/genetics/growth & development/metabolism ; Gene Expression Regulation, Developmental ; *Gene Expression Regulation, Plant ; *Genome, Plant ; Membrane Proteins/genetics/metabolism ; Phylogeny ; Plant Proteins/genetics/*metabolism ; Whole Genome Sequencing/methods ; }, abstract = {BACKGROUND: Members of the MtN3/saliva/SWEET gene family are present in various organisms and are highly conserved. Their precise biochemical functions remain unclear, especially in Chinese cabbage. Based on the whole genome sequence, this study aims to identify the MtN3/saliva/SWEETs family members in Chinese cabbage and to analyze their classification, gene structure, chromosome distribution, phylogenetic relationship, expression pattern, and biological functions.

RESULTS: We identified 34 SWEET genes in Chinese cabbage and analyzed their localization on chromosomes and transmembrane regions of their corresponding proteins. Analysis of a phylogenetic tree indicated that there were at least 17 supposed ancestor genes before the separation in Brassica rapa and Arabidopsis. The expression patterns of these genes in different tissues and flower developmental stages of Chinese cabbage showed that they are mainly involved in reproductive development. The Ka/Ks ratio between paralogous SWEET gene pairs of B. rapa were far less than 1. In our previous study, At2g39060 homologous gene Bra000116 (BraSWEET9, also named BcNS, Brassica Nectary and Stamen) played an important role during flower development in Chinese cabbage. Instantaneous expression experiments in onion epidermal cells showed that the gene encoding this protein is localized to the plasma membrane. A basal nectary split is the phenotype of transgenic plants transformed with the antisense expression vector.

CONCLUSION: This study is the first to perform a sequence analysis, structures analysis, physiological and biochemical characteristics analysis of the MtN3/saliva/SWEETs gene in Chinese cabbage and to verify the function of BcNS. A total of 34 SWEET genes were identified and they are distributed among ten chromosomes and one scaffold. The Ka/Ks ratio implies that the duplication genes suffered strong purifying selection for retention. These genes were differentially expressed in different floral organs. The phenotypes of the transgenic plants indicated that BcNs participates in the development of the floral nectary. This study provides a basis for further functional analysis of the MtN3/saliva/SWEETs gene family.}, } @article {pmid29499647, year = {2018}, author = {Brinster, R and Köttgen, A and Tayo, BO and Schumacher, M and Sekula, P and , }, title = {Control procedures and estimators of the false discovery rate and their application in low-dimensional settings: an empirical investigation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {78}, pmid = {29499647}, issn = {1471-2105}, support = {IN-1150438//DFG funding programme Open Access Publishing/International ; }, mesh = {Algorithms ; Computer Simulation ; *Empirical Research ; False Positive Reactions ; Genome-Wide Association Study ; Humans ; Polymorphism, Single Nucleotide/genetics ; Renal Insufficiency, Chronic/genetics ; }, abstract = {BACKGROUND: When many (up to millions) of statistical tests are conducted in discovery set analyses such as genome-wide association studies (GWAS), approaches controlling family-wise error rate (FWER) or false discovery rate (FDR) are required to reduce the number of false positive decisions. Some methods were specifically developed in the context of high-dimensional settings and partially rely on the estimation of the proportion of true null hypotheses. However, these approaches are also applied in low-dimensional settings such as replication set analyses that might be restricted to a small number of specific hypotheses. The aim of this study was to compare different approaches in low-dimensional settings using (a) real data from the CKDGen Consortium and (b) a simulation study.

RESULTS: In both application and simulation FWER approaches were less powerful compared to FDR control methods, whether a larger number of hypotheses were tested or not. Most powerful was the q-value method. However, the specificity of this method to maintain true null hypotheses was especially decreased when the number of tested hypotheses was small. In this low-dimensional situation, estimation of the proportion of true null hypotheses was biased.

CONCLUSIONS: The results highlight the importance of a sizeable data set for a reliable estimation of the proportion of true null hypotheses. Consequently, methods relying on this estimation should only be applied in high-dimensional settings. Furthermore, if the focus lies on testing of a small number of hypotheses such as in replication settings, FWER methods rather than FDR methods should be preferred to maintain high specificity.}, } @article {pmid29499643, year = {2018}, author = {Huang, X and Anderle, P and Hostettler, L and Baumann, MU and Surbek, DV and Ontsouka, EC and Albrecht, C}, title = {Identification of placental nutrient transporters associated with intrauterine growth restriction and pre-eclampsia.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {173}, pmid = {29499643}, issn = {1471-2164}, support = {35900//NCCR TransCure/International ; 310030_149958//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; }, mesh = {ATP Binding Cassette Transporter 1/genetics/*metabolism ; Adult ; Amino Acid Transport Systems, Neutral/genetics/*metabolism ; Case-Control Studies ; Computational Biology/methods ; Female ; Fetal Growth Retardation/genetics/metabolism/*pathology ; Fusion Regulatory Protein 1, Light Chains/genetics/*metabolism ; Gene Expression Regulation, Developmental ; Humans ; Infant, Newborn ; Placenta/metabolism/*pathology ; Pre-Eclampsia/genetics/metabolism/*pathology ; Pregnancy ; Young Adult ; }, abstract = {BACKGROUND: Gestational disorders such as intrauterine growth restriction (IUGR) and pre-eclampsia (PE) are main causes of poor perinatal outcomes worldwide. Both diseases are related with impaired materno-fetal nutrient transfer, but the crucial transport mechanisms underlying IUGR and PE are not fully elucidated. In this study, we aimed to identify membrane transporters highly associated with transplacental nutrient deficiencies in IUGR/PE.

RESULTS: In silico analyses on the identification of differentially expressed nutrient transporters were conducted using seven eligible microarray datasets (from Gene Expression Omnibus), encompassing control and IUGR/PE placental samples. Thereby 46 out of 434 genes were identified as potentially interesting targets. They are involved in the fetal provision with amino acids, carbohydrates, lipids, vitamins and microelements. Targets of interest were clustered into a substrate-specific interaction network by using Search Tool for the Retrieval of Interacting Genes. The subsequent wet-lab validation was performed using quantitative RT-PCR on placentas from clinically well-characterized IUGR/PE patients (IUGR, n = 8; PE, n = 5; PE+IUGR, n = 10) and controls (term, n = 13; preterm, n = 7), followed by 2D-hierarchical heatmap generation. Statistical evaluation using Kruskal-Wallis tests was then applied to detect significantly different expression patterns, while scatter plot analysis indicated which transporters were predominantly influenced by IUGR or PE, or equally affected by both diseases. Identified by both methods, three overlapping targets, SLC7A7, SLC38A5 (amino acid transporters), and ABCA1 (cholesterol transporter), were further investigated at the protein level by western blotting. Protein analyses in total placental tissue lysates and membrane fractions isolated from disease and control placentas indicated an altered functional activity of those three nutrient transporters in IUGR/PE.

CONCLUSIONS: Combining bioinformatic analysis, molecular biological experiments and mathematical diagramming, this study has demonstrated systematic alterations of nutrient transporter expressions in IUGR/PE. Among 46 initially targeted transporters, three significantly regulated genes were further investigated based on the severity and the disease specificity for IUGR and PE. Confirmed by mRNA and protein expression, the amino acid transporters SLC7A7 and SLC38A5 showed marked differences between controls and IUGR/PE and were regulated by both diseases. In contrast, ABCA1 may play an exclusive role in the development of PE.}, } @article {pmid29499642, year = {2018}, author = {Retchless, AC and Kretz, CB and Chang, HY and Bazan, JA and Abrams, AJ and Norris Turner, A and Jenkins, LT and Trees, DL and Tzeng, YL and Stephens, DS and MacNeil, JR and Wang, X}, title = {Expansion of a urethritis-associated Neisseria meningitidis clade in the United States with concurrent acquisition of N. gonorrhoeae alleles.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {176}, pmid = {29499642}, issn = {1471-2164}, support = {R01 AI107116/AI/NIAID NIH HHS/United States ; R01 AI127863/AI/NIAID NIH HHS/United States ; R21 AI128313/AI/NIAID NIH HHS/United States ; }, mesh = {Alleles ; Female ; Genome, Bacterial ; Gonorrhea/epidemiology/genetics/*microbiology ; Humans ; Male ; Meningococcal Infections/*epidemiology/genetics/microbiology ; Neisseria gonorrhoeae/*genetics/isolation & purification ; Neisseria meningitidis/classification/genetics/isolation & purification/physiology ; Phylogeny ; Recombination, Genetic ; United States/epidemiology ; Urethritis/*complications/genetics ; Whole Genome Sequencing/methods ; }, abstract = {BACKGROUND: Increased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the "U.S. NmNG urethritis clade". Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015.

RESULTS: The earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected.

CONCLUSIONS: Interspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the frequency with which it causes urethritis.}, } @article {pmid29499182, year = {2018}, author = {Itoh, K and Akimoto, Y and Kondo, S and Ichimiya, T and Aoki, K and Tiemeyer, M and Nishihara, S}, title = {Glucuronylated core 1 glycans are required for precise localization of neuromuscular junctions and normal formation of basement membranes on Drosophila muscles.}, journal = {Developmental biology}, volume = {436}, number = {2}, pages = {108-124}, pmid = {29499182}, issn = {1095-564X}, support = {P41 GM103490/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antigens, Tumor-Associated, Carbohydrate/*metabolism ; Basement Membrane/*metabolism ; Blotting, Western ; Drosophila/genetics ; Drosophila Proteins/*metabolism ; Glucuronosyltransferase/metabolism ; Immunoblotting ; Larva/metabolism ; Mass Spectrometry ; Muscles/*metabolism ; Neuromuscular Junction/*metabolism ; Phenotype ; Polysaccharides/metabolism ; Real-Time Polymerase Chain Reaction ; }, abstract = {T antigen (Galβ1-3GalNAcα1-Ser/Thr) is an evolutionary-conserved mucin-type core 1 glycan structure in animals synthesized by core 1 β1,3-galactosyltransferase 1 (C1GalT1). Previous studies showed that T antigen produced by Drosophila C1GalT1 (dC1GalT1) was expressed in various tissues and dC1GalT1 loss in larvae led to various defects, including decreased number of circulating hemocytes, hyper-differentiation of hematopoietic stem cells in lymph glands, malformation of the central nervous system, mislocalization of neuromuscular junction (NMJ) boutons, and ultrastructural abnormalities in NMJs and muscle cells. Although glucuronylated T antigen (GlcAβ1-3Galβ1-3GalNAcα1-Ser/Thr) has been identified in Drosophila, the physiological function of this structure has not yet been clarified. In this study, for the first time, we unraveled biological roles of glucuronylated T antigen. Our data show that in Drosophila, glucuronylation of T antigen is predominantly carried out by Drosophila β1,3-glucuronyltransferase-P (dGlcAT-P). We created dGlcAT-P null mutants and found that mutant larvae showed lower expression of glucuronylated T antigen on the muscles and at NMJs. Furthermore, mislocalization of NMJ boutons and a partial loss of the basement membrane components collagen IV (Col IV) and nidogen (Ndg) at the muscle 6/7 boundary were observed. Those two phenotypes were correlated and identical to previously described phenotypes in dC1GalT1 mutant larvae. In addition, dGlcAT-P null mutants exhibited fewer NMJ branches on muscles 6/7. Moreover, ultrastructural analysis revealed that basement membranes that lacked Col IV and Ndg were significantly deformed. We also found that the loss of dGlcAT-P expression caused ultrastructural defects in NMJ boutons. Finally, we showed a genetic interaction between dGlcAT-P and dC1GalT1. Therefore, these results demonstrate that glucuronylated core 1 glycans synthesized by dGlcAT-P are key modulators of NMJ bouton localization, basement membrane formation, and NMJ arborization on larval muscles.}, } @article {pmid29499106, year = {2018}, author = {Royauté, R and Wilson, ES and Helm, BR and Mallinger, RE and Prasifka, J and Greenlee, KJ and Bowsher, JH}, title = {Phenotypic integration in an extended phenotype: among-individual variation in nest-building traits of the alfalfa leafcutting bee (Megachile rotundata).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {7}, pages = {944-956}, doi = {10.1111/jeb.13259}, pmid = {29499106}, issn = {1420-9101}, abstract = {Structures such as nests and burrows are an essential component of many organisms' life-cycle and require a complex sequence of behaviours. Because behaviours can vary consistently among individuals and be correlated with one another, we hypothesized that these structures would (1) show evidence of among-individual variation, (2) be organized into distinct functional modules and (3) show evidence of trade-offs among functional modules due to limits on energy budgets. We tested these hypotheses using the alfalfa leafcutting bee, Megachile rotundata, a solitary bee and important crop pollinator. Megachile rotundata constructs complex nests by gathering leaf materials to form a linear series of cells in pre-existing cavities. In this study, we examined variation in the following nest construction traits: reproduction (number of cells per nest and nest length), nest protection (cap length and number of leaves per cap), cell construction (cell size and number of leaves per cell) and cell provisioning (cell mass) from 60 nests. We found a general decline in investment in cell construction and provisioning with each new cell built. In addition, we found evidence for both repeatability and plasticity in cell provisioning with little evidence for trade-offs among traits. Instead, most traits were positively, albeit weakly, correlated (r ~ 0.15), and traits were loosely organized into covarying modules. Our results show that individual differences in nest construction are detectable at a level similar to that of other behavioural traits and that these traits are only weakly integrated. This suggests that nest components are capable of independent evolutionary trajectories.}, } @article {pmid29499104, year = {2018}, author = {Culumber, ZW and Tobler, M}, title = {Correlated evolution of thermal niches and functional physiology in tropical freshwater fishes.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {722-734}, doi = {10.1111/jeb.13260}, pmid = {29499104}, issn = {1420-9101}, abstract = {The role of ecology in phenotypic and species diversification is widely documented. Nonetheless, numerous nonadaptive processes can shape realized niches and phenotypic variation in natural populations, complicating inferences about adaptive evolution at macroevolutionary scales. We tested for evolved differences in thermal tolerances and their association with the realized thermal niche (including metrics describing diurnal and seasonal patterns of temperature extremes and variability) across a genus of tropical freshwater fishes reared in a standardized environment. There was limited evolution along the thermal niche axis associated with variation in maximum temperature and in upper thermal limits. In contrast, there was considerable diversification along the first major axis of the thermal niche associated with minimum temperatures and in lower thermal limits. Across our adaptive landscape analyses, 70% of species exhibited evidence of divergence in thermal niches. Most importantly, the first two major axes of thermal niche variation were significantly correlated with variation in lower thermal limits. Our results indicate adaptation to divergent thermal niches and adaptive evolution of related functional traits, and highlight the importance of divergence in lower thermal limits for the evolution of tropical biodiversity.}, } @article {pmid29498745, year = {2018}, author = {Teri, A and Sottotetti, S and Biffi, A and Girelli, D and D'Accico, M and Arghittu, M and Colombo, C and Corti, F and Pizzamiglio, G and Cariani, L}, title = {Molecular typing of Burkholderia cepacia complex isolated from patients attending an Italian Cystic Fibrosis Centre.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {141-144}, pmid = {29498745}, issn = {1121-7138}, mesh = {Burkholderia Infections/epidemiology/*microbiology ; Burkholderia cepacia complex/classification/*genetics/*isolation & purification ; Cystic Fibrosis/*complications ; Humans ; Italy/epidemiology ; Pharmacogenomic Variants ; }, abstract = {Bacteria from the Burkholderia cepacia complex (Bcc) are capable of causing severe infections in patients with cystic fibrosis (CF). Bcc infection is often extremely difficult to treat due to its intrinsic resistance to multiple antibiotics. In addition, it seems to speed up the decline of lung function and is considered a contraindication for lung transplantation in CF. This study investigates the species of the Bcc strains recovered from chronically infected CF subjects by means of: isolation, identification methods and complete recA nucleotide sequences of 151 samples. Molecular typing showed that B. cenocepacia III is the dominant strain found in the group of subjects being treated at the Milan CF Centre (Italy) and that the infection is chronically maintained by the same species. Defining species by means of molecular analysis yields important information for the clinician in order to establish the most appropriate therapy and implement correct measures for prevention of transmission among CF subjects.}, } @article {pmid29498744, year = {2018}, author = {Pantanella, F and Iebba, V and Mura, F and Dini, L and Totino, V and Neroni, B and Bonfiglio, G and Maria, T and Passariello, C and Schippa, S}, title = {Behaviour of Bdellovibrio bacteriovorus in the presence of Gram-positive Staphylococcus aureus.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {145-152}, pmid = {29498744}, issn = {1121-7138}, mesh = {Bdellovibrio bacteriovorus/*physiology ; Coculture Techniques ; Microscopy, Electron, Scanning ; Pseudomonas aeruginosa/*virology ; Staphylococcus aureus/*virology ; Streptococcus mutans/*virology ; }, abstract = {The present study aimed to characterize the behavior of Bdellovibrio bacteriovorus in the presence of Staphylococcus aureus. B. bacteriovorus was co-cultured with S. aureus or Pseudomonas aeruginosa or Streptococcus mutans, in planktonic and sessile conditions. Co-cultures were studied by Field-Emission Scanning Electron Microscopy (FESEM), Scanning Transmission Electron Microscopy (STEM), turbidimetry, quantitative PCR (qPCR), and sequencing of gene Bd0108 of B. bacteriovorus. Results indicated that B. bacteriovorus comparably inhibited planktonic growth of P. aeruginosa and S. aureus, but not of S. mutans. FESEM and STEM showed that B. bacteriovorus interacts with S. aureus affecting its cell wall and membrane. Sequencing of gene Bd0108 did not reveal any of the mutations that can arise from the host-interaction (hit) locus. Although some Gram-negative species are reported to be B. bacteriovorus prey, it seems that in case of nutrient deficiency this predatory bacterium can also take advantage of some Gram-positive species. B. bacteriovorus behaviour in the presence of S. aureus is relevant for its possible therapeutic use in several pathologies, like cystic fibrosis in which S. aureus and P. aeruginosa frequently coexist as infectious agents.}, } @article {pmid29498743, year = {2018}, author = {Salata, C and Munegato, D and Martelli, F and Parolin, C and Calistri, A and Baritussio, A and Palù, G}, title = {Amiodarone affects Ebola virus binding and entry into target cells.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {162-164}, pmid = {29498743}, issn = {1121-7138}, mesh = {Amiodarone/*pharmacology ; Animals ; Anti-Arrhythmia Agents/pharmacology ; Cercopithecus aethiops ; Ebolavirus/*drug effects/*physiology ; HEK293 Cells ; Humans ; Vero Cells ; Virus Attachment/*drug effects ; Virus Internalization/*drug effects ; }, abstract = {Ebola Virus Disease is one of the most lethal transmissible infections characterized by a high fatality rate. Several research studies have aimed to identify effective antiviral agents. Amiodarone, a drug used for the treatment of arrhythmias, has been shown to inhibit filovirus infection in vitro by acting at the early step of the viral replication cycle. Here we demonstrate that amiodarone reduces virus binding to target cells and slows down the progression of the viral particles along the endocytic pathway. Overall our data support the notion that amiodarone interferes with Ebola virus infection by affecting cellular pathways/ targets involved in the viral entry process.}, } @article {pmid29498742, year = {2018}, author = {Colella, E and Cattaneo, D and Galli, L and Baldelli, S and Clementi, E and Galli, M and Lazzarin, A and Castagna, A and Rusconi, S and Spagnuolo, V}, title = {Potential associations between atazanavir exposure and clinical outcome: a pharmacokinetic sub-study from the MODAt randomized trial.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {106-111}, pmid = {29498742}, issn = {1121-7138}, mesh = {Adult ; Antiretroviral Therapy, Highly Active ; Atazanavir Sulfate/*pharmacokinetics/*therapeutic use ; Female ; HIV Infections/blood/*drug therapy ; HIV Protease Inhibitors/administration & dosage/blood/*pharmacokinetics/*therapeutic use ; Humans ; Male ; Middle Aged ; Treatment Failure ; }, abstract = {The 96-week results of the Monotherapy Once a Day with Atazanavir/r (MODAt) study [NCT01511809] showed an inferior virological efficacy of atazanavir (ATV)/ritonavir monotherapy versus triple therapy, which was promptly retrieved by the reintroduction of nucleoside/nucleotide inhibitors of reverse transcriptase [N(n)RTIs]. We aimed to identify potential relationships between ATV exposure and clinical outcome in HIV-1 subjects treated with ATV/ritonavir monotherapy [ATV/r 300/100 mg] versus ATV/ritonavir triple therapy [ATV/r 300/100 mg+2NRTIs]. A chromatographic method coupled with tandem mass spectrometry was applied to analyze ATV plasma concentrations in a pharmacokinetic sub-study from the MODAt trial. Mixed linear models were used to examine the ATV plasma concentration trend during follow-up and to assess the association between ATV plasma concentrations trajectories with the study arm or the occurrence of treatment failure or drugrelated adverse events or the grading of baseline total bilirubin (<3 vs ≥3). The analyses were performed using SAS Software, release 9.4 (SAS Institute, Cary, NC, USA). Overall, ATV plasma Ctrough concentration did not vary during follow-up (slope: +0.75 ng/mL/week, 95%CI: -0.97 to 2.47, p=0.387); trajectories did not differ between study arms (p=0.527). The unadjusted model-based means (95%CI) of ATV Ctrough during follow-up were 835 (95%CI: 657-1012) ng/ml in the ATV/r monotherapy arm as compared to 911 (95%CI: 740-1082) ng/mL in the ATV/r triple therapy arm (p=0.621). Mean ATV Ctrough was similar in subjects with or without adverse events (AEs). Subjects treated with ATV/r monotherapy showed significantly higher ATV concentrations as compared to subjects without adverse events or treated with ATV/r triple therapy. ATV concentrations were associated with the grading of baseline total bilirubin and the occurrence of drug-related AEs but not with HCV infection. Our findings showed a lack of association between ATV concentrations and treatment failure both in ATV/r monotherapy and triple therapy. Conversely, these data emphasized that ATV concentrations are associated with the development of side-effects in both subjects treated with ATV/r monotherapy and subjects treated with ATV/r triple therapy.}, } @article {pmid29498741, year = {2018}, author = {Valeriani, F and Crognale, S and Protano, C and Gianfranceschi, G and Orsini, M and Vitali, M and Spica, VR}, title = {Metagenomic analysis of bacterial community in a travertine depositing hot spring.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {126-135}, pmid = {29498741}, issn = {1121-7138}, mesh = {Bacteria/*genetics/isolation & purification ; Biodiversity ; Computational Biology ; DNA, Bacterial/genetics ; Hot Springs/*microbiology ; Metagenomics/*methods ; Phylogeny ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; *Water Microbiology ; }, abstract = {Several factors influence bacteria biodiversity in hot springs. The impact of biotic and abiotic pathways on travertine deposition plays a key role in microbial ecology and in the final composition of the waterborne microbiota. The metabolism of some bacterial groups such as photoautotrophs or lithoautotrophs influences water chemistry, favoring carbonate precipitation processes. The role of microbial mats in mineral precipitation processes is not fully clarified. For the first time, a comprehensive metagenomic analysis has been undertaken in the historical Bullicame hot spring. Bacterial biodiversity was characterized and biomineralization activities were assigned to different genera. A higher biodiversity in mat samples compared to water samples was observed: Shannon index of 3.34 and 0.86, respectively. Based on the functional assignment of each Operational Taxonomic Unit, the bacteria involved in biologically- induced mineralization are prevalent in mat and released in the water. According to the principle that each geothermal water specimen has distinctive physic-chemical characteristics, our results suggest new interacting bio-actions within these ecosystems. The saturation index and the chemical composition, as the high concentration of sulfur species and HCO3, can be linked to create a selective environment where pioneer communities are able to live and shape the ecosystem.}, } @article {pmid29498740, year = {2018}, author = {Freer, G and Pistello, M}, title = {Varicella-zoster virus infection: natural history, clinical manifestations, immunity and current and future vaccination strategies.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {95-105}, pmid = {29498740}, issn = {1121-7138}, mesh = {Chickenpox/*prevention & control/virology ; Chickenpox Vaccine/*immunology ; Herpes Zoster/*prevention & control/virology ; Humans ; Vaccination ; Vaccines, Attenuated ; }, abstract = {Varicella-zoster virus (VZV) is the etiologic agent of varicella (chicken pox), a childhood exanthematic disease that develops as a result of primary infection, and zoster (shingles), caused by reactivation of the virus persisting in a latent form in the dorsal sensory ganglia. Although varicella is generally a mild self-limiting illness, in immunocompromised subjects and adults it can have a serious clinical course that can lead to permanent damage of the central nervous system. In these and in most zoster cases, treatment with anti-herpetic drugs and/or immunotherapy is necessary. Because it is highly contagious, varicella is one of the most common exanthematic diseases. It is preventable by vaccination with an attenuated vaccine administered around the first year of age, and with a boost vaccination in school age. This article briefly describes the natural history and pathophysiology of VZV infection and its current epidemiology and provides an overview of current and future vaccine options to protect against varicella and/or zoster.}, } @article {pmid29498739, year = {2018}, author = {Foschi, C and Salvo, M and Galli, S and Moroni, A and Cevenini, R and Marangoni, A}, title = {Prevalence and antimicrobial resistance of genital Mollicutes in Italy over a two-year period.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {153-158}, pmid = {29498739}, issn = {1121-7138}, mesh = {Adolescent ; Adult ; Anti-Bacterial Agents/*pharmacology ; Child ; Child, Preschool ; Drug Resistance, Bacterial ; Female ; Genital Diseases, Female/epidemiology/*microbiology ; Genital Diseases, Male/epidemiology/*microbiology ; Humans ; Infant ; Italy/epidemiology ; Male ; Middle Aged ; Mycoplasma Infections/drug therapy/epidemiology/microbiology ; Mycoplasma hominis/*drug effects ; Prevalence ; Tenericutes/*drug effects ; Ureaplasma Infections/drug therapy/epidemiology/microbiology ; Ureaplasma urealyticum/*drug effects ; Young Adult ; }, abstract = {Knowledge of the prevalence and antimicrobial susceptibility of genital Mollicutes is crucial to offer guidelines for empirical treatments. The aim of this study was to investigate the prevalence and the resistance profile of Mycoplasma hominis (MH) and Ureaplasma urealyticum/Ureaplasma parvum (UU/UP) in genital samples over a two-year period in Bologna, Italy. From January 2015 to December 2016, data on all the subjects providing uro-genital specimens for Mollicutes detection by culture were analyzed. A total of 4660 subjects (84.4% females) were enrolled and an overall Mollicutes prevalence of 30.9% was found. Women turned positive for Mollicutes infection twice as often as men (33.3% vs 17.8%) and the detection rate progressively decreased with increasing age. Ureaplasmas represented the commonest species isolated (overall prevalence: 24.2%), whereas mixed infections (6.5%) and MH single infections (3.9%) were far less common. Ureaplasma species showed significant levels of quinolone resistance, especially to ciprofloxacin (77%), whereas MH strains were non-susceptible to azithromycin and roxithromycin in about 90% of cases. Mollicutes co-infections showed a more severe resistance pattern than single infections. Over time, the resistance rate for azithromycin and roxithromycin increased significantly. Globally, our results revealed that minocycline and doxycycline can still be first-line drugs for Mollicutes treatment.}, } @article {pmid29498738, year = {2018}, author = {Angelici, MC and Nardis, C and Scarpelli, R and Ade, P}, title = {Blastocystis hominis transmission by non-potable water: a case report in Italy.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {173-177}, pmid = {29498738}, issn = {1121-7138}, mesh = {Adult ; Blastocystis Infections/*parasitology/pathology/therapy/transmission ; Blastocystis hominis/*isolation & purification ; Humans ; Italy ; Male ; Probiotics/therapeutic use ; Water/*parasitology ; }, abstract = {In the reported case, a 41-year-old Italian man came to the clinician's observation reporting cramps, bloating and watery diarrhoea a few days after drinking water indicated as unpotable from a fountain in a farm area. The medical suspicion was directed at both gluten intolerance and enteric infection, eventually of waterborne origin. Gluten intolerance was investigated by intestinal biopsy and excluded, while stool analyses ruled out infective bacteriological or viral agents and parasites. Subsequently, a persistent eosinophilia was revealed and a parasitological analysis was again suggested, planning for a more sensitive molecular method. Therefore, a multiplex-PCR of enteric protozoa species DNA was performed on an intestinal biopsy and faecal samples revealing only Blastocystis hominis protozoa, subsequently typed as subtype 1 by RFLP-PCR method. B. hominis is an anaerobic protozoa found in the human and animal intestinal tract, recently associated with a pathogenic role characterized by chronic development. Since blastocystosis has been demonstrated as a waterborne infection, a sample of water matrix was analysed, revealing the B. hominis subtype 1 DNA inside. A probable water transmission of Blastocystis infection has been demonstrated in this case report. Only a probiotic treatment based on Saccharomyces boulardii was administered to the patient and this apparently resolved the infection. In summary, the case described here is a chronic blastocystosis of possible waterborne origin, controlled by assuming a yeast treatment.}, } @article {pmid29498621, year = {2018}, author = {Chen, WM and Xie, PB and Hsu, MY and Sheu, SY}, title = {Parvibium lacunae gen. nov., sp. nov., a new member of the family Alcaligenaceae isolated from a freshwater pond.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1291-1299}, doi = {10.1099/ijsem.0.002667}, pmid = {29498621}, issn = {1466-5034}, mesh = {Alcaligenaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Hydroxybutyrates/metabolism ; Phospholipids/chemistry ; *Phylogeny ; Polyesters/metabolism ; Ponds/*microbiology ; Putrescine/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Taiwan ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A bacterial strain designated KMB9T was isolated from a freshwater pond in Taiwan and characterized using a polyphasic taxonomy approach. Cells of strain KMB9T were Gram-stain-negative, aerobic, poly-β-hydroxybutyrate-accumulating, motile by means of a monopolar flagellum, non-spore-forming and rods surrounded by a thick capsule and forming white-coloured colonies. Growth occurred at 20-40 °C (optimum, 25-37 °C), at pH 6.5-7.5 (optimum, pH 7.0) and with 0-0.5 % NaCl (optimum, 0 %). Phylogenetic analyses based on 16S rRNA gene and four housekeeping gene sequences (recA, rpoA, rpoB and atpD) showed that strain KMB9T forms a distinct phyletic line within the family Alcaligenaceae, and the levels of 16S rRNA gene sequence similarity to its closest relatives with validly published names were less than 93.3 %. The predominant fatty acids were summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), C16 : 0 and C18 : 1ω7c. The major isoprenoid quinone was Q-8. The major polyamine was putrescine. The polar lipid profile revealed the presence of phosphatidylethanolamine, phosphatidylglycerol and several uncharacterized aminophospholipids, aminolipids, phospholipids and lipids. The genomic DNA G+C content of strain KMB9T was 54.5 mol%. On the basis of the genotypic and phenotypic data, strain KMB9T represents a novel species of a new genus in the family Alcaligenaceae, for which the name Parvibium lacunae gen. nov., sp. nov. is proposed. The type strain is KMB9T (=BCRC 81053T=LMG 30055T=KCTC 52814T).}, } @article {pmid29498618, year = {2018}, author = {Chen, WM and Su, CL and Young, CC and Sheu, SY}, title = {Flavobacterium fluviatile sp. nov., isolated from a freshwater creek.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1244-1250}, doi = {10.1099/ijsem.0.002659}, pmid = {29498618}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Fresh Water/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Polyamines/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Taiwan ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A yellowish-pink-coloured bacterial strain, TAPY14T, was isolated from a freshwater creek in Taiwan. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TAPY14T belonged to the genus Flavobacterium and showed the highest similarity (97.3 %) with respect to Flavobacterium reichenbachii WB 3.2-61T, Flavobacterium ginsengisoli DCY54T and Flavobacterium defluvii EMB117T and less than 97 % with other members of the genus. Cells of strain TAPY14T were Gram-stain-negative, strictly aerobic, motile by gliding and rod-shaped. Optimal growth occurred at 20-30 °C, pH 6 and in the presence of 0.5 % NaCl. Strain TAPY14T contained iso-C15 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) as the predominant fatty acids. The polar lipid profile consisted of phosphatidylethanolamine, four uncharacterized aminophospholipids, one uncharacterized phospholipid and one uncharacterized lipid. The major polyamine was homospermidine. The major isoprenoid quinone was MK-6. The DNA G+C content of the genomic DNA was 38.1 mol%. The DNA-DNA hybridization values for strain TAPY14T with F. reichenbachii DSM 21791T, F. ginsengisoli JCM 17336T and F. defluvii DSM 17963T were less than 30 %. On the basis of the phylogenetic inference and phenotypic data, strain TAPY14T should be classified as a novel species, for which the name Flavobacterium fluviatile sp. nov. is proposed. The type strain is TAPY14T (=BCRC 81012T=LMG 29733T=KCTC 52446T).}, } @article {pmid29498617, year = {2018}, author = {Li, FN and Tuo, L and Lee, SM and Jin, T and Liao, S and Li, W and Yan, X and Sun, CH}, title = {Amnibacterium endophyticum sp. nov., an endophytic actinobacterium isolated from Aegiceras corniculatum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1327-1332}, doi = {10.1099/ijsem.0.002676}, pmid = {29498617}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Aminobutyrates/chemistry ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Primulaceae/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {A Gram-stain-positive, aerobic, non-motile, non-spore-forming and short-rod-shaped actinobacterium, designated strain 1T4Z-3T, was isolated from a piece of surface-sterilized branch of Aegiceras corniculatum collected from the Cotai Ecological Zones in Macao, China. Comparative 16S rRNA gene sequence analysis showed that strain 1T4Z-3T was clearly affiliated to the genus Amnibacterium and exhibited 97.9 % gene sequence similarity to Amnibacterium kyonggiense JCM 16463T, 97.3 % gene sequence similarity to Amnibacterium soli JCM 19015T and less than 96.4 % gene sequence similarities to other genera of the family Microbacteriaceae. Strain 1T4Z-3T had L-2,4-diaminobutyric acid as the diagnostic cell-wall diamino acid. The major fatty acids (>10 % of total fatty acids) were iso-C16 : 0 (46.6 %) and anteiso-C15 : 0 (27.3 %). The predominant menaquinones of strain 1T4Z-3T were MK-11 (81.4 %) and MK-12 (14.1 %). The polar lipids comprised diphosphatidylglycerol, phosphatidylglycerol, six unidentified glycolipids, four unidentified phospholipids and two unidentified lipids. The DNA G+C content of strain 1T4Z-3T was 71.4 mol%. Based on the phylogenetic, phenotypic and chemotaxonomic features, strain 1T4Z-3T is considered to represent a novel species of the genus Amnibacterium, for which the name Amnibacterium endophyticum sp. nov. is proposed. The type strain of Amnibacterium endophyticum is 1T4Z-3T (=KCTC 39983T=CGMCC 1.16066T).}, } @article {pmid29498616, year = {2018}, author = {Schumann, P and Zhang, DC and França, L and Margesin, R}, title = {Marmoricola silvestris sp. nov., a novel actinobacterium isolated from alpine forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1313-1318}, doi = {10.1099/ijsem.0.002674}, pmid = {29498616}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; *Forests ; Italy ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {A Gram-stain-positive, flagellated, catalase- and cytochrome c oxidase-positive bacterial strain, designated S20-100T, was isolated from alpine forest soil. Growth occurred at a temperature range of 0-30 °C, at pH 6-9 and in the presence of 0-1 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain S20-100T was related to the genus Marmoricola and had the highest 16S rRNA gene sequence similarity to Marmoricola ginsengisoli Gsoil 097T (98.4 %) and Marmoricola solisilvae KIS18-7T (98.3 %). The cell-wall peptidoglycan of strain S20-100T contained ll-diaminopimelic acid (ll-Dpm) as the diagnostic diamino acid and was of the type A3γ ll-Dpm - Gly. The strain contained MK-8(H4) as the predominant isoprenoid quinone and diphosphatidylglycerol, phosphatidylglycerol, four unidentified phospholipids and three unidentified lipids in lower amounts. The major cellular fatty acids (>10 %) were iso-C16 : 0, C17 : 1ω6c and C18 : 1ω9c. The genomic DNA G+C content was 66.2 mol%. Combined data of phylogenetic, phenotypic and chemotaxonomic analyses demonstrated that strain S20-100T represents a novel species of the genus Marmoricola, for which the name Marmoricola silvestris sp. nov. is proposed. The type strain is S20-100T (=DSM 104694T=LMG 30008T).}, } @article {pmid29498615, year = {2018}, author = {Santos, ARO and Leon, MP and Barros, KO and Freitas, LFD and Hughes, AFS and Morais, PB and Lachance, MA and Rosa, CA}, title = {Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., sp. nov., Starmerella opuntiae f.a., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a., sp. nov., isolated from flowers and bees, and transfer of related Candida species to the genus Starmerella as new combinations.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1333-1343}, doi = {10.1099/ijsem.0.002675}, pmid = {29498615}, issn = {1466-5034}, mesh = {Animals ; Bees/*microbiology ; Belize ; Brazil ; Candida/classification ; Costa Rica ; DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Flowers/*microbiology ; *Phylogeny ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; }, abstract = {Six novel yeast species, Starmerella camargoi f.a., sp. nov., Starmerella ilheusensis f.a., sp. nov., Starmerella litoralis f.a., Starmerella opuntiae f.a., sp. nov., sp. nov., Starmerella roubikii f.a., sp. nov. and Starmerella vitae f.a, sp. nov. are proposed to accommodate 19 isolates recovered from ephemeral flowers or bees in Brazil, Costa Rica and Belize. Sequence analysis of the ITS-5.8S region (when available) and the D1/D2 domains of the large subunit of the rRNA gene showed that the six novel yeasts are phylogenetically related to several species of the Starmerella clade. The type strains are Starmerella camargoi f.a., sp. nov. UFMG-CM-Y595T (=CBS 14130T; Mycobank number MB 822640), Starmerella ilheusensis f.a., sp. nov. UFMG-CM-Y596T (=CBS CBS14131T; MB 822641), Starmerella litoralis f.a., sp. nov. UFMG-CM-Y603T (=CBS14104T; MB 822642), Starmerella opuntiae f.a., sp. nov. UFMG-CM-Y286T (=CBS 13466T; MB 822643), Starmerella roubikii f.a., sp. nov. UWOPS 01-191.1 (=CBS 15148; MB 822645) and Starmerella vitae f.a., sp. nov. UWOPS 00-107.2 (=CBS 15147T; MB 822646). In addition, 25 species currently assigned to the genus Candida are reassigned formally to the genus Starmerella.}, } @article {pmid29498432, year = {2018}, author = {Fuchs, AJ and Zamora, AJ and Zintel, TM}, title = {The third annual Northeastern Evolutionary Primatologists meeting at Yale University.}, journal = {Evolutionary anthropology}, volume = {27}, number = {2}, pages = {68-70}, doi = {10.1002/evan.21574}, pmid = {29498432}, issn = {1520-6505}, } @article {pmid29498211, year = {2018}, author = {Durand, S and Loiseau, V and Prigot, C and Braquart-Varnier, C and Beltran-Bech, S}, title = {Producing offspring in Armadillidium vulgare: Effects of genetic diversity and inbreeding.}, journal = {Evolution & development}, volume = {20}, number = {2}, pages = {65-77}, doi = {10.1111/ede.12248}, pmid = {29498211}, issn = {1525-142X}, mesh = {Animals ; Female ; Fertility ; Genetic Fitness ; Genetic Variation ; Inbreeding ; Isopoda/*physiology ; Male ; Mating Preference, Animal ; Reproduction ; Selection, Genetic ; Sexual Behavior, Animal ; Survival Analysis ; }, abstract = {Genetic diversity is known to be correlated to fitness traits, and inbred individuals often display lower values for life history traits. In this study, we attempt to quantify how inbreeding affects such traits in the terrestrial isopod Armadillidium vulgare by performing inbred and non-inbred crosses under laboratory conditions. We estimated genetic characteristics of parents and offspring, and related them to fecundity and fertility measures, as well as offspring growth and survival. Our study shows that a decrease in offspring number might result from mortality around birth, but not to changes in fecundity, fertilization rate, or developmental failure between inbred and non-inbred crosses. More heterozygous females tended to be bigger and had a higher fecundity, which could have implications in mate choice. No effect of inbreeding was detected on offspring growth and survival. These results can be related to previously observed effects of genetic characteristics on mating strategies in A. vulgare, and could shed light on mechanisms of inbreeding avoidance in this species.}, } @article {pmid29498143, year = {2018}, author = {Behie, AM}, title = {Remembering an amazing scientist and friend, Colin Groves (1942 - 2017).}, journal = {Evolutionary anthropology}, volume = {27}, number = {2}, pages = {62-63}, doi = {10.1002/evan.21577}, pmid = {29498143}, issn = {1520-6505}, mesh = {Animals ; *Anthropology ; Australia ; Biological Evolution ; *Classification ; Conservation of Natural Resources ; History, 20th Century ; History, 21st Century ; Humans ; London ; Male ; Primates ; }, } @article {pmid29497218, year = {2018}, author = {Malcicka, M and Visser, B and Ellers, J}, title = {An Evolutionary Perspective on Linoleic Acid Synthesis in Animals.}, journal = {Evolutionary biology}, volume = {45}, number = {1}, pages = {15-26}, pmid = {29497218}, issn = {0071-3260}, abstract = {The diet of organisms generally provides a sufficient supply of energy and building materials for healthy growth and development, but should also contain essential nutrients. Species differ in their exogenous requirements, but it is not clear why some species are able to synthesize essential nutrients, while others are not. The unsaturated fatty acid, linoleic acid (LA; 18:2n-6) plays an important role in functions such as cell physiology, immunity, and reproduction, and is an essential nutrient in diverse organisms. LA is readily synthesized in bacteria, protozoa and plants, but it was long thought that all animals lacked the ability to synthesize LA de novo and thus required a dietary source of this fatty acid. Over the years, however, an increasing number of studies have shown active LA synthesis in animals, including insects, nematodes and pulmonates. Despite continued interest in LA metabolism, it has remained unclear why some organisms can synthesize LA while others cannot. Here, we review the mechanisms by which LA is synthesized and which biological functions LA supports in different organisms to answer the question why LA synthesis was lost and repeatedly gained during the evolution of distinct invertebrate groups. We propose several hypotheses and compile data from the available literature to identify which factors promote LA synthesis within a phylogenetic framework. We have not found a clear link between our proposed hypotheses and LA synthesis; therefore we suggest that LA synthesis may be facilitated through bifunctionality of desaturase enzymes or evolved through a combination of different selective pressures.}, } @article {pmid29497217, year = {2018}, author = {Svensson, EI}, title = {On Reciprocal Causation in the Evolutionary Process.}, journal = {Evolutionary biology}, volume = {45}, number = {1}, pages = {1-14}, pmid = {29497217}, issn = {0071-3260}, abstract = {Recent calls for a revision of standard evolutionary theory (SET) are based partly on arguments about the reciprocal causation. Reciprocal causation means that cause-effect relationships are bi-directional, as a cause could later become an effect and vice versa. Such dynamic cause-effect relationships raise questions about the distinction between proximate and ultimate causes, as originally formulated by Ernst Mayr. They have also motivated some biologists and philosophers to argue for an Extended Evolutionary Synthesis (EES). The EES will supposedly expand the scope of the Modern Synthesis (MS) and SET, which has been characterized as gene-centred, relying primarily on natural selection and largely neglecting reciprocal causation. Here, I critically examine these claims, with a special focus on the last conjecture. I conclude that reciprocal causation has long been recognized as important by naturalists, ecologists and evolutionary biologists working in the in the MS tradition, although it it could be explored even further. Numerous empirical examples of reciprocal causation in the form of positive and negative feedback are now well known from both natural and laboratory systems. Reciprocal causation have also been explicitly incorporated in mathematical models of coevolutionary arms races, frequency-dependent selection, eco-evolutionary dynamics and sexual selection. Such dynamic feedback were already recognized by Richard Levins and Richard Lewontin in their bok The Dialectical Biologist. Reciprocal causation and dynamic feedback might also be one of the few contributions of dialectical thinking and Marxist philosophy in evolutionary theory. I discuss some promising empirical and analytical tools to study reciprocal causation and the implications for the EES. Finally, I briefly discuss how quantitative genetics can be adapated to studies of reciprocal causation, constructive inheritance and phenotypic plasticity and suggest that the flexibility of this approach might have been underestimated by critics of contemporary evolutionary biology.}, } @article {pmid29496962, year = {2018}, author = {Godula, K}, title = {Following sugar patterns in search of galectin function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2548-2550}, pmid = {29496962}, issn = {1091-6490}, support = {DP2 HD087954/HD/NICHD NIH HHS/United States ; P01 HL107150/HL/NHLBI NIH HHS/United States ; R21 AI129894/AI/NIAID NIH HHS/United States ; }, mesh = {Carbohydrates ; Galectin 1 ; *Galectins ; Protein Binding ; *Sugars ; }, } @article {pmid29496961, year = {2018}, author = {Kisielnicka, E and Minasaki, R and Eckmann, CR}, title = {MAPK signaling couples SCF-mediated degradation of translational regulators to oocyte meiotic progression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2772-E2781}, pmid = {29496961}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/genetics/metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Cycle Proteins/genetics/metabolism ; MAP Kinase Signaling System ; Meiosis/*physiology ; Mitogen-Activated Protein Kinase 1/genetics/metabolism ; Oocytes/metabolism/*physiology ; Oogenesis/physiology ; Phosphorylation ; Protein Processing, Post-Translational ; RNA-Binding Proteins/genetics/*metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; }, abstract = {RNA-binding proteins (RBPs) are important regulators of gene expression programs, especially during gametogenesis. How the abundance of particular RBPs is restricted to defined stages of meiosis remains largely elusive. Here, we report a molecular pathway that subjects two nonrelated but broadly evolutionarily conserved translational regulators (CPB-3/CPEB and GLD-1/STAR) to proteosomal degradation in Caenorhabditis elegans germ cells at the transition from pachytene to diplotene of meiotic prophase. Both RBPs are recognized by the same ubiquitin ligase complex, containing the molecular scaffold Cullin-1 and the tumor suppressor SEL-10/FBXW7 as its substrate recognition subunit. Destabilization of either RBP through this Skp, Cullin, F-box-containing complex (SCF) ubiquitin ligase appears to loosen its negative control over established target mRNAs, and presumably depends on a prior phosphorylation of CPB-3 and GLD-1 by MAPK (MPK-1), whose activity increases in mid- to late pachytene to promote meiotic progression and oocyte differentiation. Thus, we propose that the orchestrated degradation of RBPs via MAPK-signaling cascades during germ cell development may act to synchronize meiotic with sexual differentiation gene expression changes.}, } @article {pmid29496960, year = {2018}, author = {Kraay, ANM and Brouwer, AF and Lin, N and Collender, PA and Remais, JV and Eisenberg, JNS}, title = {Modeling environmentally mediated rotavirus transmission: The role of temperature and hydrologic factors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2782-E2790}, pmid = {29496960}, issn = {1091-6490}, support = {R01 TW010286/TW/FIC NIH HHS/United States ; K01 AI091864/AI/NIAID NIH HHS/United States ; R01 AI125842/AI/NIAID NIH HHS/United States ; U01 GM110712/GM/NIGMS NIH HHS/United States ; R01 AI050038/AI/NIAID NIH HHS/United States ; }, mesh = {Disease Outbreaks ; Ecuador/epidemiology ; Fresh Water ; Humans ; Hydrology/methods ; Incidence ; *Models, Theoretical ; Rotavirus/pathogenicity ; Rotavirus Infections/epidemiology/*transmission ; Temperature ; Tropical Climate ; }, abstract = {Rotavirus is considered a directly transmitted disease due to its high infectivity. Environmental pathways have, therefore, largely been ignored. Rotavirus, however, persists in water sources, and both its surface water concentrations and infection incidence vary with temperature. Here, we examine the potential for waterborne rotavirus transmission. We use a mechanistic model that incorporates both direct and waterborne transmission pathways, coupled with a hydrological model, and we simulate rotavirus transmission between two communities with interconnected water sources. To parameterize temperature dependency, we estimated temperature-dependent decay rates in water through a meta-analysis. Our meta-analysis suggests that rotavirus decay rates are positively associated with temperature (n = 39, P [Formula: see text] 0.001). This association is stronger at higher temperatures (over 20 °C), consistent with tropical climate conditions. Our model analysis demonstrates that water could disseminate rotavirus between the two communities for all modeled temperatures. While direct transmission was important for disease amplification within communities, waterborne transmission could also amplify transmission. In standing-water systems, the modeled increase in decay led to decreased disease, with every 1 °C increase in temperature leading to up to a 2.4% decrease in incidence. These effect sizes are consistent with prior meta-analyses, suggesting that environmental transmission through water sources may partially explain the observed associations between temperature and rotavirus incidence. Waterborne rotavirus transmission is likely most important in cooler seasons and in communities that use slow-moving or stagnant water sources. Even when indirect transmission through water cannot sustain outbreaks, it can seed outbreaks that are maintained by high direct transmission rates.}, } @article {pmid29496959, year = {2018}, author = {Ofotokun, I}, title = {Deciphering how HIV-1 weakens and cracks the bone.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2551-2553}, pmid = {29496959}, issn = {1091-6490}, mesh = {*Bone and Bones ; *HIV-1 ; Stress, Mechanical ; }, } @article {pmid29496958, year = {2018}, author = {Spanton, EM and Zibrov, AA and Zhou, H and Taniguchi, T and Watanabe, K and Zaletel, MP and Young, AF}, title = {Observation of fractional Chern insulators in a van der Waals heterostructure.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {62-66}, doi = {10.1126/science.aan8458}, pmid = {29496958}, issn = {1095-9203}, abstract = {Topologically ordered phases are characterized by long-range quantum entanglement and fractional statistics rather than by symmetry breaking. First observed in a fractionally filled continuum Landau level, topological order has since been proposed to arise more generally at fractional fillings of topologically nontrivial Chern bands. Here we report the observation of gapped states at fractional fillings of Harper-Hofstadter bands arising from the interplay of a magnetic field and a superlattice potential in a bilayer graphene-hexagonal boron nitride heterostructure. We observed phases at fractional filling of bands with Chern indices [Formula: see text] Some of these phases, in [Formula: see text] and [Formula: see text] bands, are characterized by fractional Hall conductance-that is, they are known as fractional Chern insulators and constitute an example of topological order beyond Landau levels.}, } @article {pmid29496957, year = {2018}, author = {Kaplanis, J and Gordon, A and Shor, T and Weissbrod, O and Geiger, D and Wahl, M and Gershovits, M and Markus, B and Sheikh, M and Gymrek, M and Bhatia, G and MacArthur, DG and Price, AL and Erlich, Y}, title = {Quantitative analysis of population-scale family trees with millions of relatives.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {171-175}, doi = {10.1126/science.aam9309}, pmid = {29496957}, issn = {1095-9203}, support = {R01 MH101244/MH/NIMH NIH HHS/United States ; R03 HG006731/HG/NHGRI NIH HHS/United States ; }, mesh = {Datasets as Topic ; *Family ; *Genealogy and Heraldry ; Humans ; Longevity ; *Models, Genetic ; *Pedigree ; Population ; }, abstract = {Family trees have vast applications in fields as diverse as genetics, anthropology, and economics. However, the collection of extended family trees is tedious and usually relies on resources with limited geographical scope and complex data usage restrictions. We collected 86 million profiles from publicly available online data shared by genealogy enthusiasts. After extensive cleaning and validation, we obtained population-scale family trees, including a single pedigree of 13 million individuals. We leveraged the data to partition the genetic architecture of human longevity and to provide insights into the geographical dispersion of families. We also report a simple digital procedure to overlay other data sets with our resource.}, } @article {pmid29496882, year = {2018}, author = {Chakrabarty, P}, title = {My year as a fed.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1066}, doi = {10.1126/science.359.6379.1066}, pmid = {29496882}, issn = {1095-9203}, } @article {pmid29496881, year = {2018}, author = {Moriyama, S and Brestoff, JR and Flamar, AL and Moeller, JB and Klose, CSN and Rankin, LC and Yudanin, NA and Monticelli, LA and Putzel, GG and Rodewald, HR and Artis, D}, title = {β2-adrenergic receptor-mediated negative regulation of group 2 innate lymphoid cell responses.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1056-1061}, doi = {10.1126/science.aan4829}, pmid = {29496881}, issn = {1095-9203}, support = {F32 DK109630/DK/NIDDK NIH HHS/United States ; F32 AI134018/AI/NIAID NIH HHS/United States ; R01 AI061570/AI/NIAID NIH HHS/United States ; R21 AI087990/AI/NIAID NIH HHS/United States ; R01 AI074878/AI/NIAID NIH HHS/United States ; R21 AI083480/AI/NIAID NIH HHS/United States ; R01 AI095466/AI/NIAID NIH HHS/United States ; U01 AI095608/AI/NIAID NIH HHS/United States ; R01 AI102942/AI/NIAID NIH HHS/United States ; R01 AI097333/AI/NIAID NIH HHS/United States ; }, mesh = {*Adaptive Immunity ; Adrenergic Neurons/*immunology ; Adrenergic beta-2 Receptor Agonists/pharmacology ; Animals ; Humans ; *Immunity, Innate ; Inflammation/immunology ; Intestines/immunology ; Lung/immunology ; Lymphocytes/*metabolism ; Mice ; Mice, Inbred C57BL ; Nerve Net/immunology ; Receptors, Adrenergic, beta-2/genetics/*metabolism ; Signal Transduction ; }, abstract = {The type 2 inflammatory response is induced by various environmental and infectious stimuli. Although recent studies identified group 2 innate lymphoid cells (ILC2s) as potent sources of type 2 cytokines, the molecular pathways controlling ILC2 responses are incompletely defined. Here we demonstrate that murine ILC2s express the β2-adrenergic receptor (β2AR) and colocalize with adrenergic neurons in the intestine. β2AR deficiency resulted in exaggerated ILC2 responses and type 2 inflammation in intestinal and lung tissues. Conversely, β2AR agonist treatment was associated with impaired ILC2 responses and reduced inflammation in vivo. Mechanistically, we demonstrate that the β2AR pathway is a cell-intrinsic negative regulator of ILC2 responses through inhibition of cell proliferation and effector function. Collectively, these data provide the first evidence of a neuronal-derived regulatory circuit that limits ILC2-dependent type 2 inflammation.}, } @article {pmid29496880, year = {2018}, author = {Lu, P and Min, D and DiMaio, F and Wei, KY and Vahey, MD and Boyken, SE and Chen, Z and Fallas, JA and Ueda, G and Sheffler, W and Mulligan, VK and Xu, W and Bowie, JU and Baker, D}, title = {Accurate computational design of multipass transmembrane proteins.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1042-1046}, doi = {10.1126/science.aaq1739}, pmid = {29496880}, issn = {1095-9203}, support = {R01 GM063919/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bioengineering ; Computer Simulation ; Crystallography, X-Ray ; Cytoplasm/metabolism ; Detergents ; HEK293 Cells ; Humans ; Membrane Proteins/*chemistry/metabolism ; Models, Chemical ; Protein Engineering/*methods ; Protein Folding ; Protein Multimerization ; Protein Stability ; Protein Structure, Secondary ; Protein Unfolding ; }, abstract = {The computational design of transmembrane proteins with more than one membrane-spanning region remains a major challenge. We report the design of transmembrane monomers, homodimers, trimers, and tetramers with 76 to 215 residue subunits containing two to four membrane-spanning regions and up to 860 total residues that adopt the target oligomerization state in detergent solution. The designed proteins localize to the plasma membrane in bacteria and in mammalian cells, and magnetic tweezer unfolding experiments in the membrane indicate that they are very stable. Crystal structures of the designed dimer and tetramer-a rocket-shaped structure with a wide cytoplasmic base that funnels into eight transmembrane helices-are very close to the design models. Our results pave the way for the design of multispan membrane proteins with new functions.}, } @article {pmid29496879, year = {2018}, author = {Sockolosky, JT and Trotta, E and Parisi, G and Picton, L and Su, LL and Le, AC and Chhabra, A and Silveria, SL and George, BM and King, IC and Tiffany, MR and Jude, K and Sibener, LV and Baker, D and Shizuru, JA and Ribas, A and Bluestone, JA and Garcia, KC}, title = {Selective targeting of engineered T cells using orthogonal IL-2 cytokine-receptor complexes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1037-1042}, pmid = {29496879}, issn = {1095-9203}, support = {T32 AI007290/AI/NIAID NIH HHS/United States ; R43 AI072905/AI/NIAID NIH HHS/United States ; R35 CA197633/CA/NCI NIH HHS/United States ; R37 AI051321/AI/NIAID NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/*immunology ; CD8-Positive T-Lymphocytes/*immunology ; Cell Engineering/*methods ; HEK293 Cells ; Humans ; Immunotherapy, Adoptive/*methods ; Melanoma, Experimental ; Mice ; Neoplasms/*therapy ; Receptors, Interleukin-2/genetics/*immunology ; }, abstract = {Interleukin-2 (IL-2) is a cytokine required for effector T cell expansion, survival, and function, especially for engineered T cells in adoptive cell immunotherapy, but its pleiotropy leads to simultaneous stimulation and suppression of immune responses as well as systemic toxicity, limiting its therapeutic use. We engineered IL-2 cytokine-receptor orthogonal (ortho) pairs that interact with one another, transmitting native IL-2 signals, but do not interact with their natural cytokine and receptor counterparts. Introduction of orthoIL-2Rβ into T cells enabled the selective cellular targeting of orthoIL-2 to engineered CD4+ and CD8+ T cells in vitro and in vivo, with limited off-target effects and negligible toxicity. OrthoIL-2 pairs were efficacious in a preclinical mouse cancer model of adoptive cell therapy and may therefore represent a synthetic approach to achieving selective potentiation of engineered cells.}, } @article {pmid29496878, year = {2018}, author = {Fleming-Davies, AE and Williams, PD and Dhondt, AA and Dobson, AP and Hochachka, WM and Leon, AE and Ley, DH and Osnas, EE and Hawley, DM}, title = {Incomplete host immunity favors the evolution of virulence in an emergent pathogen.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1030-1033}, doi = {10.1126/science.aao2140}, pmid = {29496878}, issn = {1095-9203}, support = {R01 GM105245/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Bird Diseases/*microbiology/*prevention & control ; Evolution, Molecular ; *Finches ; Host-Pathogen Interactions/*immunology ; *Immunologic Memory ; Models, Immunological ; Mycoplasma Infections/*microbiology ; Mycoplasma gallisepticum/*genetics/*pathogenicity ; Virulence/genetics ; }, abstract = {Immune memory evolved to protect hosts from reinfection, but incomplete responses that allow future reinfection may inadvertently select for more-harmful pathogens. We present empirical and modeling evidence that incomplete immunity promotes the evolution of higher virulence in a natural host-pathogen system. We performed sequential infections of house finches with Mycoplasma gallisepticum strains of various levels of virulence. Virulent bacterial strains generated stronger host protection against reinfection than less virulent strains and thus excluded less virulent strains from infecting previously exposed hosts. In a two-strain model, the resulting fitness advantage selected for an almost twofold increase in pathogen virulence. Thus, the same immune systems that protect hosts from infection can concomitantly drive the evolution of more-harmful pathogens in nature.}, } @article {pmid29496877, year = {2018}, author = {Athalye, VR and Santos, FJ and Carmena, JM and Costa, RM}, title = {Evidence for a neural law of effect.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1024-1029}, doi = {10.1126/science.aao6058}, pmid = {29496877}, issn = {1095-9203}, support = {//European Research Council/International ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Dopamine/pharmacology/physiology ; Dopaminergic Neurons/*physiology ; Learning/*physiology ; Male ; Mice ; Mice, Transgenic ; Motor Cortex/*physiology ; Optogenetics ; *Reinforcement (Psychology) ; Ventral Tegmental Area/*physiology ; }, abstract = {Thorndike's law of effect states that actions that lead to reinforcements tend to be repeated more often. Accordingly, neural activity patterns leading to reinforcement are also reentered more frequently. Reinforcement relies on dopaminergic activity in the ventral tegmental area (VTA), and animals shape their behavior to receive dopaminergic stimulation. Seeking evidence for a neural law of effect, we found that mice learn to reenter more frequently motor cortical activity patterns that trigger optogenetic VTA self-stimulation. Learning was accompanied by gradual shaping of these patterns, with participating neurons progressively increasing and aligning their covariance to that of the target pattern. Motor cortex patterns that lead to phasic dopaminergic VTA activity are progressively reinforced and shaped, suggesting a mechanism by which animals select and shape actions to reliably achieve reinforcement.}, } @article {pmid29496876, year = {2018}, author = {McMahon, WJ and Davies, NS}, title = {Evolution of alluvial mudrock forced by early land plants.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1022-1024}, doi = {10.1126/science.aan4660}, pmid = {29496876}, issn = {1095-9203}, abstract = {Mudrocks are a primary archive of Earth's history from the Archean eon to recent times, and their source-to-sink production and deposition play a central role in long-term ocean chemistry and climate regulation. Using original and published stratigraphic data from all 704 of Earth's known alluvial formations from the Archean eon (3.5 billion years ago) to the Carboniferous period (0.3 billion years ago), we prove contentions of an upsurge in the proportion of mud retained on land coeval with vegetation evolution. We constrain the onset of the upsurge to the Ordovician-Silurian and show that alluvium deposited after land plant evolution contains a proportion of mudrock that is, on average, 1.4 orders of magnitude greater than the proportion contained in alluvium from the preceding 90% of Earth's history. We attribute this shift to the ways in which vegetation revolutionized mud production and sediment flux from continental interiors.}, } @article {pmid29496875, year = {2018}, author = {Hong, SY and Park, Y and Hwang, Y and Kim, YB and Baik, MH and Chang, S}, title = {Selective formation of γ-lactams via C-H amidation enabled by tailored iridium catalysts.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1016-1021}, doi = {10.1126/science.aap7503}, pmid = {29496875}, issn = {1095-9203}, abstract = {Intramolecular insertion of metal nitrenes into carbon-hydrogen bonds to form γ-lactam rings has traditionally been hindered by competing isocyanate formation. We report the application of theory and mechanism studies to optimize a class of pentamethylcyclopentadienyl iridium(III) catalysts for suppression of this competing pathway. Modulation of the stereoelectronic properties of the auxiliary bidentate ligands to be more electron-donating was suggested by density functional theory calculations to lower the C-H insertion barrier favoring the desired reaction. These catalysts transform a wide range of 1,4,2-dioxazol-5-ones, carbonylnitrene precursors easily accessible from carboxylic acids, into the corresponding γ-lactams via sp3 and sp2 C-H amidation with exceptional selectivity. The power of this method was further demonstrated by the successful late-stage functionalization of amino acid derivatives and other bioactive molecules.}, } @article {pmid29496874, year = {2018}, author = {Lamb, CT and Festa-Bianchet, M and Boyce, MS}, title = {Invest long term in Canada's wilderness.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1002}, doi = {10.1126/science.aat1104}, pmid = {29496874}, issn = {1095-9203}, mesh = {Canada ; *Investments ; *Wilderness ; }, } @article {pmid29496873, year = {2018}, author = {Bladon, KD}, title = {Rethinking wildfires and forest watersheds.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1001-1002}, doi = {10.1126/science.aar8120}, pmid = {29496873}, issn = {1095-9203}, mesh = {*Forests ; *Wildfires ; }, } @article {pmid29496872, year = {2018}, author = {Moreira, F and Pe'er, G}, title = {Agricultural policy can reduce wildfires.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1001}, doi = {10.1126/science.aat1359}, pmid = {29496872}, issn = {1095-9203}, mesh = {Agriculture/*trends ; *Environmental Policy ; European Union ; Wildfires/*prevention & control ; }, } @article {pmid29496871, year = {2018}, author = {Mehling, MA and Metcalf, GE and Stavins, RN}, title = {Linking climate policies to advance global mitigation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {997-998}, doi = {10.1126/science.aar5988}, pmid = {29496871}, issn = {1095-9203}, } @article {pmid29496870, year = {2018}, author = {Özdemir, ŞK}, title = {Fermi arcs connect topological degeneracies.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {995-996}, doi = {10.1126/science.aar8210}, pmid = {29496870}, issn = {1095-9203}, } @article {pmid29496869, year = {2018}, author = {Fischer, WW}, title = {Early plants and the rise of mud.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {994-995}, doi = {10.1126/science.aas9886}, pmid = {29496869}, issn = {1095-9203}, mesh = {Biological Evolution ; *Plants ; }, } @article {pmid29496868, year = {2018}, author = {Kim, JS}, title = {Microbial warfare against viruses.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {993}, doi = {10.1126/science.aas9430}, pmid = {29496868}, issn = {1095-9203}, mesh = {Bacteria/*genetics ; Bacteriophages ; *Viruses ; }, } @article {pmid29496867, year = {2018}, author = {Montell, C}, title = {pHirst sour taste channels pHound?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {991-992}, pmid = {29496867}, issn = {1095-9203}, support = {R01 DC007864/DC/NIDCD NIH HHS/United States ; }, mesh = {Calcium Channels ; Humans ; *Taste ; *Taste Buds ; }, } @article {pmid29496866, year = {2018}, author = {Mackall, CL}, title = {Engineering a designer immunotherapy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {990-991}, doi = {10.1126/science.aas9434}, pmid = {29496866}, issn = {1095-9203}, mesh = {*Engineering ; *Immunotherapy ; }, } @article {pmid29496865, year = {2018}, author = {Willis, KJ and Jeffers, ES and Tovar, C}, title = {What makes a terrestrial ecosystem resilient?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {988-989}, doi = {10.1126/science.aar5439}, pmid = {29496865}, issn = {1095-9203}, mesh = {*Conservation of Natural Resources ; *Ecosystem ; }, } @article {pmid29496864, year = {2018}, author = {Darling, ES and Côté, IM}, title = {Seeking resilience in marine ecosystems.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {986-987}, doi = {10.1126/science.aas9852}, pmid = {29496864}, issn = {1095-9203}, mesh = {*Climate Change ; *Conservation of Natural Resources ; *Coral Reefs ; }, } @article {pmid29496863, year = {2018}, author = {Pennisi, E}, title = {Nature's strategies: A plant that stands and fights.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {985}, doi = {10.1126/science.359.6379.985}, pmid = {29496863}, issn = {1095-9203}, mesh = {Animals ; *Insecta ; Nicotine/*metabolism ; *Tobacco/growth & development/metabolism/parasitology ; }, } @article {pmid29496862, year = {2018}, author = {Leslie, M}, title = {Nature's strategies: Squirrels with a rainy day fund.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {982}, doi = {10.1126/science.359.6379.982}, pmid = {29496862}, issn = {1095-9203}, mesh = {Animals ; *Energy Metabolism ; Food ; *Hibernation ; Sciuridae/metabolism/*physiology ; }, } @article {pmid29496861, year = {2018}, author = {Cornwall, W}, title = {Bending to the water's will.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {980-985}, doi = {10.1126/science.359.6379.980}, pmid = {29496861}, issn = {1095-9203}, mesh = {Animals ; Bangladesh ; *Disasters ; Endangered Species ; *Floods ; Humans ; *Rivers ; }, } @article {pmid29496860, year = {2018}, author = {Leslie, M}, title = {Nature's strategies: Stealing genes to survive.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {979}, doi = {10.1126/science.359.6379.979}, pmid = {29496860}, issn = {1095-9203}, mesh = {Adaptation, Physiological ; Drug Resistance, Bacterial/*genetics ; *Gene Transfer, Horizontal ; Humans ; Klebsiella Infections/microbiology/mortality ; Klebsiella pneumoniae/*genetics/*physiology ; }, } @article {pmid29496859, year = {2018}, author = {Pennisi, E}, title = {Nature's strategies: Resilience by regeneration.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {978}, doi = {10.1126/science.359.6379.978}, pmid = {29496859}, issn = {1095-9203}, mesh = {Ambystoma mexicanum/*physiology ; Animals ; *Regeneration ; *Resilience, Psychological ; }, } @article {pmid29496858, year = {2018}, author = {Underwood, E}, title = {Lessons in resilience.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {976-979}, doi = {10.1126/science.359.6379.976}, pmid = {29496858}, issn = {1095-9203}, mesh = {Adolescent ; Female ; Hair/*chemistry ; Humans ; Jordan ; Male ; Refugees/*psychology ; *Resilience, Psychological ; Syria ; *War Exposure ; }, } @article {pmid29496857, year = {2018}, author = {Pennisi, E}, title = {Nature's strategies: Fish that switch sex to thrive.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {975}, doi = {10.1126/science.359.6379.975}, pmid = {29496857}, issn = {1095-9203}, mesh = {*Adaptation, Physiological ; Animals ; Female ; Fishes/*physiology ; Male ; Population ; *Sex Determination Processes ; }, } @article {pmid29496856, year = {2018}, author = {Servick, K}, title = {After the deluge.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {972-975}, doi = {10.1126/science.359.6379.972}, pmid = {29496856}, issn = {1095-9203}, mesh = {Cyclonic Storms/*history ; History, 21st Century ; Humans ; Louisiana ; *Resilience, Psychological ; Social Sciences ; *Survival ; }, } @article {pmid29496855, year = {2018}, author = {Couzin-Frankel, J}, title = {The roots of resilience.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {970-971}, doi = {10.1126/science.359.6379.970}, pmid = {29496855}, issn = {1095-9203}, mesh = {*Cyclonic Storms ; Humans ; Louisiana ; *Resilience, Psychological ; Survival ; }, } @article {pmid29496854, year = {2018}, author = {Cho, A}, title = {Cosmic dawn signal holds clue to dark matter.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {969}, doi = {10.1126/science.359.6379.969}, pmid = {29496854}, issn = {1095-9203}, } @article {pmid29496853, year = {2018}, author = {Cartlidge, E}, title = {Better atomic clocks herald new era of timekeeping.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {968}, doi = {10.1126/science.359.6379.968}, pmid = {29496853}, issn = {1095-9203}, } @article {pmid29496852, year = {2018}, author = {Cohen, J}, title = {Genome editor gets more versatile and precise.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {967}, doi = {10.1126/science.359.6379.967}, pmid = {29496852}, issn = {1095-9203}, mesh = {Bacterial Proteins/*chemistry/*genetics ; CRISPR-Associated Protein 9 ; *CRISPR-Cas Systems ; *DNA Cleavage ; Endonucleases/*chemistry/*genetics ; Gene Editing/*methods ; }, } @article {pmid29496851, year = {2018}, author = {Leslie, M}, title = {Restraining immunity could lower high blood pressure.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {966-967}, doi = {10.1126/science.359.6379.966}, pmid = {29496851}, issn = {1095-9203}, mesh = {Angiotensins/pharmacology ; Animals ; Blood Pressure/drug effects/*immunology ; Disease Models, Animal ; Humans ; Hypertension/chemically induced/*drug therapy/*immunology ; Imines/*pharmacology/*therapeutic use ; Immune System/*drug effects ; Immunity ; *Immunosuppression ; Indoles/*pharmacology/*therapeutic use ; Mice ; }, } @article {pmid29496850, year = {2018}, author = {Clery, D}, title = {Arecibo telescope saved by university consortium.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {965-966}, doi = {10.1126/science.359.6379.965}, pmid = {29496850}, issn = {1095-9203}, } @article {pmid29496849, year = {2018}, author = {Larson, C}, title = {Asia's hunger for sand takes toll on ecology.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {964-965}, doi = {10.1126/science.359.6379.964}, pmid = {29496849}, issn = {1095-9203}, mesh = {Animals ; China ; *Construction Materials ; *Endangered Species ; *Extinction, Biological ; *Mining ; }, } @article {pmid29496848, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {962-963}, doi = {10.1126/science.359.6379.962}, pmid = {29496848}, issn = {1095-9203}, } @article {pmid29496847, year = {2018}, author = {Berg, J}, title = {Transparent author credit.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {961}, doi = {10.1126/science.aat4136}, pmid = {29496847}, issn = {1095-9203}, } @article {pmid29496846, year = {2018}, author = {Fortunato, S and Bergstrom, CT and Börner, K and Evans, JA and Helbing, D and Milojević, S and Petersen, AM and Radicchi, F and Sinatra, R and Uzzi, B and Vespignani, A and Waltman, L and Wang, D and Barabási, AL}, title = {Science of science.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {}, pmid = {29496846}, issn = {1095-9203}, support = {P01 AG039347/AG/NIA NIH HHS/United States ; U01 CA198934/CA/NCI NIH HHS/United States ; }, abstract = {Identifying fundamental drivers of science and developing predictive models to capture its evolution are instrumental for the design of policies that can improve the scientific enterprise-for example, through enhanced career paths for scientists, better performance evaluation for organizations hosting research, discovery of novel effective funding vehicles, and even identification of promising regions along the scientific frontier. The science of science uses large-scale data on the production of science to search for universal and domain-specific patterns. Here, we review recent developments in this transdisciplinary field.}, } @article {pmid29496823, year = {2018}, author = {Titus, MA}, title = {Myosin-Driven Intracellular Transport.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a021972}, pmid = {29496823}, issn = {1943-0264}, abstract = {The delivery of intracellular material within cells is crucial for maintaining normal function. Myosins transport a wide variety of cargo, ranging from vesicles to ribonuclear protein particles (RNPs), in plants, fungi, and metazoa. The properties of a given myosin transporter are adapted to move on different actin filament tracks, either on the disordered actin networks at the cell cortex or along highly organized actin bundles to distribute their cargo in a localized manner or move it across long distances in the cell. Transport is controlled by selective recruitment of the myosin to its cargo that also plays a role in activation of the motor.}, } @article {pmid29496542, year = {2018}, author = {O'Connell, KA and Hamidy, A and Kurniawan, N and Smith, EN and Fujita, MK}, title = {Synchronous diversification of parachuting frogs (Genus Rhacophorus) on Sumatra and Java.}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {101-112}, doi = {10.1016/j.ympev.2018.02.003}, pmid = {29496542}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification/genetics ; Bayes Theorem ; Biodiversity ; Cluster Analysis ; DNA, Mitochondrial/genetics ; Gene Flow ; Genetic Variation ; Indonesia ; *Islands ; Likelihood Functions ; *Phylogeny ; Phylogeography ; Polymorphism, Single Nucleotide/genetics ; Species Specificity ; }, abstract = {Geological and climatological processes can drive the synchronous diversification of co-distributed species. The islands of Sumatra and Java have experienced complex geological and climatological histories, including extensive sea-level changes and the formation of valleys between northern, central, and southern components of the Barisan Mountain Range, which may have promoted diversification of their resident species. We investigate diversification on these islands using 13 species of the parachuting frog genus Rhacophorus. We use both mitochondrial and nuclear sequence data, along with genome-wide SNPs to estimate phylogenetic structure and divergence times, and to test for synchronous diversification. We find support for synchronous divergence among sister-species pairs from Sumatra and Java ∼9 Ma, as well as of populations of four co-distributed taxa on Sumatra ∼5.6 Ma. We found that sister species diverged in allopatry on Sumatra and conclude that divergence on Sumatra and Java was affected by sea-level fluctuations that promoted isolation in allopatry.}, } @article {pmid29496541, year = {2018}, author = {Stubbs, RL and Folk, RA and Xiang, CL and Soltis, DE and Cellinese, N}, title = {Pseudo-parallel patterns of disjunctions in an Arctic-alpine plant lineage.}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {88-100}, doi = {10.1016/j.ympev.2018.02.016}, pmid = {29496541}, issn = {1095-9513}, mesh = {Biodiversity ; *Ecosystem ; Likelihood Functions ; North America ; *Phylogeny ; Phylogeography ; Saxifragaceae/*classification ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Disjunct distributions have intrigued biologists for centuries. Investigating these biogeographic patterns provides insight into speciation and biodiversity at multiple spatial and phylogenetic scales. Some disjunctions have been intensively studied, yet others have been largely overlooked and remain poorly understood. Among the lesser-known disjunction patterns is that between the mountain ranges of western North America. Flora and fauna endemic to the mountains of this region provide important systems for investigating causes and results of disjunctions, given the relatively recent geological formation of this area and the intense climatic fluctuations that have occurred since its formation. In Micranthes (Saxifragaceae), which has high rates of montane endemism, two species, M. bryophora and M. tolmiei, show this biogeographical pattern. By reconstructing a time-calibrated phylogeny based on 518 low-copy nuclear markers and including multiple populations of each species from the Coast Ranges, Cascades, Sierra Nevada, and Rocky Mountains, this study provides a biogeographical and temporal framework for the evolution of Micranthes in western North America. Strongly supported east-west differentiated clades are recovered for M. bryophora and M. tolmiei in both maximum likelihood and coalescent-based species tree reconstructions. Biogeographic analysis suggests different patterns of dispersal for both taxa and the dating analyses recovered contrasting ages for each clade. Due to both the different geographic patterns and the timing of the initial diversification of each taxon corresponding to different geologic and climatic events, the disjunction patterns shown for these taxa are suggested to be an example of biogeographical pseudocongruence.}, } @article {pmid29496340, year = {2018}, author = {Wilcox, TM and Schwartz, MK and Lowe, WH}, title = {Evolutionary Community Ecology: Time to Think Outside the (Taxonomic) Box.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {240-250}, doi = {10.1016/j.tree.2018.01.014}, pmid = {29496340}, issn = {1872-8383}, mesh = {*Biological Evolution ; *Classification ; Ecology/*trends ; }, abstract = {Ecologists and evolutionary biologists have long been interested in the role of interspecific competition in the diversification of clades. These studies often focus on a single taxonomic group, making the implicit assumption that important competitive interactions occur only between closely related taxa, despite abundant documentation of intense competition between species that are distantly related. Specifically, this assumption ignores convergence of distantly related competitors on limiting niche axes and thus may miss cryptic effects of distantly related competitors on the evolution of focal clades. For example, distantly related competitors may act as important drivers of niche conservatism within clades, a pattern commonly ascribed to evolutionary constraints or the abiotic environment. Here we propose an alternative model of how niche similarity evolves when the functional traits of interest are mediated by unrelated phenotypic traits, as is often the case for distantly related competitors. This model represents an important conceptual step towards a more accurate, taxonomically inclusive understanding of the role that competition plays in the micro- and macroevolution of interacting species.}, } @article {pmid29496339, year = {2018}, author = {Tong, X and Wang, R and Chen, XY}, title = {Expansion or Invasion? A Response to Nackley et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {234-235}, doi = {10.1016/j.tree.2018.02.002}, pmid = {29496339}, issn = {1872-8383}, } @article {pmid29496322, year = {2018}, author = {Gómez-Olivencia, A and Holliday, T and Madelaine, S and Couture-Veschambre, C and Maureille, B}, title = {The costal skeleton of the Regourdou 1 Neandertal.}, journal = {Journal of human evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.jhevol.2017.12.005}, pmid = {29496322}, issn = {1095-8606}, abstract = {The morphology and size of the Neandertal thorax is a subject of growing interest due to its link to general aspects of body size and shape, including physiological aspects related to bioenergetics and activity budgets. However, the number of well-preserved adult Neandertal costal remains is still low. The recent finding of new additional costal remains from the Regourdou 1 (R1) skeleton has rendered this skeleton as one of the most complete Neandertal costal skeletons with a minimum of 18 ribs represented, five of which are complete or virtually complete. Here we describe for the first time all the rib remains from R1 and compare them to a large modern Euroamerican male sample as well as to other published Neandertal individuals. The costal skeleton of this individual shows significant metric and morphological differences from our modern human male comparative sample. The perceived differences include: dorsoventrally large 1st and 2nd ribs, 3rd ribs with a very closed dorsal curvature and large maximum diameters at the posterior angle, a large tubercle-iliocostal line distance in the 4th rib, thick shafts at the dorsal end of its 6th ribs, thick mid-shafts of the 8th ribs, large articular tubercles at the 9th ribs, and thick shafts of the 11th and 12th ribs. Here we also describe a new mesosternal fragment: the left lateral half of sternebral segments 4 and 5. This portion reveals that the mesosternum of R1 had a sternal foramen in its inferiormost preserved sternal segment and supports previous estimation of the total length of this mesosternum. The new costal remains from R1 support the view that Neandertals, when compared with modern humans, show a significantly different thorax, consistent with differences found in other anatomical regions such as the vertebral column and pelvis.}, } @article {pmid29495964, year = {2018}, author = {Magrini, V and Gao, X and Rosa, BA and McGrath, S and Zhang, X and Hallsworth-Pepin, K and Martin, J and Hawdon, J and Wilson, RK and Mitreva, M}, title = {Improving eukaryotic genome annotation using single molecule mRNA sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {172}, pmid = {29495964}, issn = {1471-2164}, support = {U54HG003079/HG/NHGRI NIH HHS/United States ; U54 HG003079/HG/NHGRI NIH HHS/United States ; R01AI081803//National Institute of Allergy and Infectious Diseases/International ; R01 AI081803/AI/NIAID NIH HHS/United States ; R01GM097435/GM/NIGMS NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Eukaryota/*genetics ; *Genome ; *Genomics/methods ; *Molecular Sequence Annotation ; RNA, Messenger/*genetics ; *Sequence Analysis, DNA ; Workflow ; }, abstract = {BACKGROUND: The advantages of Pacific Biosciences (PacBio) single-molecule real-time (SMRT) technology include long reads, low systematic bias, and high consensus read accuracy. Here we use these attributes to improve on the genome annotation of the parasitic hookworm Ancylostoma ceylanicum using PacBio RNA-Seq.

RESULTS: We sequenced 192,888 circular consensus sequences (CCS) derived from cDNAs generated using the CloneTech SMARTer system. These SMARTer-SMRT libraries were normalized and size-selected providing a robust population of expressed structural genes for subsequent genome annotation. We demonstrate PacBio mRNA sequences based genome annotation improvement, compared to genome annotation using conventional sequencing-by-synthesis alone, by identifying 1609 (9.2%) new genes, extended the length of 3965 (26.7%) genes and increased the total genomic exon length by 1.9 Mb (12.4%). Non-coding sequence representation (primarily from UTRs based on dT reverse transcription priming) was particularly improved, increasing in total length by fifteen-fold, by increasing both the length and number of UTR exons. In addition, the UTR data provided by these CCS allowed for the identification of a novel SL2 splice leader sequence for A. ceylanicum and an increase in the number and proportion of functionally annotated genes. RNA-seq data also confirmed some of the newly annotated genes and gene features.

CONCLUSION: Overall, PacBio data has supported a significant improvement in gene annotation in this genome, and is an appealing alternative or complementary technique for genome annotation to the other transcript sequencing technologies.}, } @article {pmid29494845, year = {2018}, author = {Potvin-Trottier, L and Luro, S and Paulsson, J}, title = {Microfluidics and single-cell microscopy to study stochastic processes in bacteria.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {186-192}, pmid = {29494845}, issn = {1879-0364}, support = {R01 GM081563/GM/NIGMS NIH HHS/United States ; R01 GM095784/GM/NIGMS NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/metabolism/*ultrastructure ; DNA Damage ; Escherichia coli/genetics ; Microfluidics/instrumentation/*methods ; Microscopy/instrumentation/*methods ; Single-Cell Analysis/instrumentation/*methods ; Stochastic Processes ; Synthetic Biology/methods ; }, abstract = {Bacteria have molecules present in low and fluctuating numbers that randomize cell behaviors. Understanding these stochastic processes and their impact on cells has, until recently, been limited by the lack of single-cell measurement methods. Here, we review recent developments in microfluidics that enable following individual cells over long periods of time under precisely controlled conditions, and counting individual fluorescent molecules in many cells. We showcase discoveries that were made possible using these devices in various aspects of microbiology, such as antibiotic tolerance/persistence, cell-size control, cell-fate determination, DNA damage response, and synthetic biology.}, } @article {pmid29494832, year = {2018}, author = {Gómez-Schiavon, M and El-Samad, H}, title = {Complexity-aware simple modeling.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {47-52}, doi = {10.1016/j.mib.2018.01.004}, pmid = {29494832}, issn = {1879-0364}, abstract = {Mathematical models continue to be essential for deepening our understanding of biology. On one extreme, simple or small-scale models help delineate general biological principles. However, the parsimony of detail in these models as well as their assumption of modularity and insulation make them inaccurate for describing quantitative features. On the other extreme, large-scale and detailed models can quantitatively recapitulate a phenotype of interest, but have to rely on many unknown parameters, making them often difficult to parse mechanistically and to use for extracting general principles. We discuss some examples of a new approach-complexity-aware simple modeling-that can bridge the gap between the small-scale and large-scale approaches.}, } @article {pmid29494256, year = {2018}, author = {Howell, RR}, title = {From a Single Child to Uniform Newborn Screening: My Lucky Life in Pediatric Medical Genetics.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {1-14}, doi = {10.1146/annurev-genom-083117-021611}, pmid = {29494256}, issn = {1545-293X}, abstract = {Mike, a memorable young patient with untreated phenylketonuria, as well as others affected by genetic disorders that could be treated if diagnosed in infancy, launched my six-decade career. This autobiographical article reflects on my childhood, early research, and professional experiences in pediatric genetics. My laboratory research focused on inborn errors of metabolism, including the glycogen storage diseases. My effort to organize newborn screening through the recommended uniform screening panel shaped and standardized newborn screening nationwide. Looking ahead, the expansion of whole-genome and whole-exome sequencing into newborn screening raises ethical and policy issues regarding informed consent procedures and the storage and use of residual blood spots.}, } @article {pmid29494241, year = {2018}, author = {Zeymer, C and Hilvert, D}, title = {Directed Evolution of Protein Catalysts.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {131-157}, doi = {10.1146/annurev-biochem-062917-012034}, pmid = {29494241}, issn = {1545-4509}, abstract = {Directed evolution is a powerful technique for generating tailor-made enzymes for a wide range of biocatalytic applications. Following the principles of natural evolution, iterative cycles of mutagenesis and screening or selection are applied to modify protein properties, enhance catalytic activities, or develop completely new protein catalysts for non-natural chemical transformations. This review briefly surveys the experimental methods used to generate genetic diversity and screen or select for improved enzyme variants. Emphasis is placed on a key challenge, namely how to generate novel catalytic activities that expand the scope of natural reactions. Two particularly effective strategies, exploiting catalytic promiscuity and rational design, are illustrated by representative examples of successfully evolved enzymes. Opportunities for extending these approaches to more complex biocatalytic systems are also considered.}, } @article {pmid29494240, year = {2018}, author = {Clevers, H and Watt, FM}, title = {Defining Adult Stem Cells by Function, not by Phenotype.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {1015-1027}, doi = {10.1146/annurev-biochem-062917-012341}, pmid = {29494240}, issn = {1545-4509}, abstract = {Central to the classical hematopoietic stem cell (HSC) paradigm is the concept that the maintenance of blood cell numbers is exclusively executed by a discrete physical entity: the transplantable HSC. The HSC paradigm has served as a stereotypic template in stem cell biology, yet the search for rare, hardwired professional stem cells has remained futile in most other tissues. In a more open approach, the focus on the search for stem cells as a physical entity may need to be replaced by the search for stem cell function, operationally defined as the ability of an organ to replace lost cells. The nature of such a cell may be different under steady state conditions and during tissue repair. We discuss emerging examples including the renewal strategies of the skin, gut epithelium, liver, lung, and mammary gland in comparison with those of the hematopoietic system. While certain key housekeeping and developmental signaling pathways are shared between different stem cell systems, there may be no general, deeper principles underlying the renewal mechanisms of the various individual tissues.}, } @article {pmid29494239, year = {2018}, author = {Islam, MS and Leissing, TM and Chowdhury, R and Hopkinson, RJ and Schofield, CJ}, title = {2-Oxoglutarate-Dependent Oxygenases.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {585-620}, doi = {10.1146/annurev-biochem-061516-044724}, pmid = {29494239}, issn = {1545-4509}, support = {BB/L009846/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {2-Oxoglutarate (2OG)-dependent oxygenases (2OGXs) catalyze a remarkably diverse range of oxidative reactions. In animals, these comprise hydroxylations and N-demethylations proceeding via hydroxylation; in plants and microbes, they catalyze a wider range including ring formations, rearrangements, desaturations, and halogenations. The catalytic flexibility of 2OGXs is reflected in their biological functions. After pioneering work identified the roles of 2OGXs in collagen biosynthesis, research revealed they also function in plant and animal development, transcriptional regulation, nucleic acid modification/repair, fatty acid metabolism, and secondary metabolite biosynthesis, including of medicinally important antibiotics. In plants, 2OGXs are important agrochemical targets and catalyze herbicide degradation. Human 2OGXs, particularly those regulating transcription, are current therapeutic targets for anemia and cancer. Here, we give an overview of the biochemistry of 2OGXs, providing examples linking to biological function, and outline how knowledge of their enzymology is being exploited in medicine, agrochemistry, and biocatalysis.}, } @article {pmid29494238, year = {2018}, author = {Yang, W and Gao, Y}, title = {Translesion and Repair DNA Polymerases: Diverse Structure and Mechanism.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {239-261}, pmid = {29494238}, issn = {1545-4509}, support = {ZIA DK036146-10/NULL/Intramural NIH HHS/United States ; ZIA DK075037-08/NULL/Intramural NIH HHS/United States ; }, abstract = {The number of DNA polymerases identified in each organism has mushroomed in the past two decades. Most newly found DNA polymerases specialize in translesion synthesis and DNA repair instead of replication. Although intrinsic error rates are higher for translesion and repair polymerases than for replicative polymerases, the specialized polymerases increase genome stability and reduce tumorigenesis. Reflecting the numerous types of DNA lesions and variations of broken DNA ends, translesion and repair polymerases differ in structure, mechanism, and function. Here, we review the unique and general features of polymerases specialized in lesion bypass, as well as in gap-filling and end-joining synthesis.}, } @article {pmid29494237, year = {2018}, author = {Storck, EM and Özbalci, C and Eggert, US}, title = {Lipid Cell Biology: A Focus on Lipids in Cell Division.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {839-869}, doi = {10.1146/annurev-biochem-062917-012448}, pmid = {29494237}, issn = {1545-4509}, abstract = {Cells depend on hugely diverse lipidomes for many functions. The actions and structural integrity of the plasma membrane and most organelles also critically depend on membranes and their lipid components. Despite the biological importance of lipids, our understanding of lipid engagement, especially the roles of lipid hydrophobic alkyl side chains, in key cellular processes is still developing. Emerging research has begun to dissect the importance of lipids in intricate events such as cell division. This review discusses how these structurally diverse biomolecules are spatially and temporally regulated during cell division, with a focus on cytokinesis. We analyze how lipids facilitate changes in cellular morphology during division and how they participate in key signaling events. We identify which cytokinesis proteins are associated with membranes, suggesting lipid interactions. More broadly, we highlight key unaddressed questions in lipid cell biology and techniques, including mass spectrometry, advanced imaging, and chemical biology, which will help us gain insights into the functional roles of lipids.}, } @article {pmid29493660, year = {2018}, author = {Grunspan, DZ and Nesse, RM and Barnes, ME and Brownell, SE}, title = {Core principles of evolutionary medicine: A Delphi study.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {13-23}, pmid = {29493660}, issn = {2050-6201}, abstract = {Background and objectives: Evolutionary medicine is a rapidly growing field that uses the principles of evolutionary biology to better understand, prevent and treat disease, and that uses studies of disease to advance basic knowledge in evolutionary biology. Over-arching principles of evolutionary medicine have been described in publications, but our study is the first to systematically elicit core principles from a diverse panel of experts in evolutionary medicine. These principles should be useful to advance recent recommendations made by The Association of American Medical Colleges and the Howard Hughes Medical Institute to make evolutionary thinking a core competency for pre-medical education.

Methodology: The Delphi method was used to elicit and validate a list of core principles for evolutionary medicine. The study included four surveys administered in sequence to 56 expert panelists. The initial open-ended survey created a list of possible core principles; the three subsequent surveys winnowed the list and assessed the accuracy and importance of each principle.

Results: Fourteen core principles elicited at least 80% of the panelists to agree or strongly agree that they were important core principles for evolutionary medicine. These principles over-lapped with concepts discussed in other articles discussing key concepts in evolutionary medicine.

Conclusions and implications: This set of core principles will be helpful for researchers and instructors in evolutionary medicine. We recommend that evolutionary medicine instructors use the list of core principles to construct learning goals. Evolutionary medicine is a young field, so this list of core principles will likely change as the field develops further.}, } @article {pmid29493627, year = {2018}, author = {Mehrabi, Z and Jimenez, D and Jarvis, A}, title = {Smallholders need access to big-data agronomy too.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {30}, doi = {10.1038/d41586-018-02566-1}, pmid = {29493627}, issn = {1476-4687}, } @article {pmid29493626, year = {2018}, author = {Leeming, J}, title = {Enter our 'scientist at work' photo contest.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {131}, doi = {10.1038/d41586-018-02406-2}, pmid = {29493626}, issn = {1476-4687}, } @article {pmid29493625, year = {2018}, author = {Annan, K}, title = {Data can help to end malnutrition across Africa.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {7}, doi = {10.1038/d41586-018-02386-3}, pmid = {29493625}, issn = {1476-4687}, mesh = {Africa/epidemiology ; Child ; Child Nutrition Sciences ; Data Collection ; Geographic Mapping ; Goals ; Growth Disorders/epidemiology/prevention & control ; Humans ; Hunger ; Malnutrition/*epidemiology/*prevention & control ; Nutritional Status ; Poverty/prevention & control/statistics & numerical data ; United Nations ; }, } @article {pmid29493623, year = {2018}, author = {}, title = {A code of ethics to get scientists talking.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {5}, doi = {10.1038/d41586-018-02516-x}, pmid = {29493623}, issn = {1476-4687}, mesh = {Anecdotes as Topic ; *Codes of Ethics ; *Communication ; *Ethics, Research ; Research Personnel/*ethics/*psychology ; }, } @article {pmid29493621, year = {2018}, author = {}, title = {Nature journals announce two steps to improve transparency.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {6}, doi = {10.1038/d41586-018-02563-4}, pmid = {29493621}, issn = {1476-4687}, mesh = {*Editorial Policies ; Humans ; Periodicals as Topic ; *Publishing ; }, } @article {pmid29493619, year = {2018}, author = {Padma, TV}, title = {Indian scientist's sacking spotlights sexual harassment.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {16}, doi = {10.1038/d41586-018-02249-x}, pmid = {29493619}, issn = {1476-4687}, mesh = {Confidentiality ; Fear ; Female ; Humans ; India ; Male ; Research Personnel/*legislation & jurisprudence/*psychology ; Sexual Harassment/*legislation & jurisprudence/*prevention & control ; *Truth Disclosure ; Workplace ; }, } @article {pmid29493618, year = {2018}, author = {Reich, BJ and Haran, M}, title = {Precision maps for public health.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {32-33}, doi = {10.1038/d41586-018-02096-w}, pmid = {29493618}, issn = {1476-4687}, mesh = {*Public Health ; }, } @article {pmid29493617, year = {2018}, author = {Fraser, B}, title = {China's lust for jaguar fangs imperils big cats.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {13-14}, doi = {10.1038/d41586-018-02314-5}, pmid = {29493617}, issn = {1476-4687}, mesh = {Animal Fur ; Animals ; Animals, Wild/anatomy & histology ; Cattle ; China ; Commerce/*economics/*legislation & jurisprudence ; Conservation of Natural Resources ; Crime/*legislation & jurisprudence/prevention & control ; Livestock ; Panthera/*anatomy & histology ; Population Dynamics ; Predatory Behavior ; Skull ; South America ; *Tooth ; }, } @article {pmid29493616, year = {2018}, author = {Guglielmi, G}, title = {Florida residents could soon get the power to alter science classes.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {15}, doi = {10.1038/d41586-018-02434-y}, pmid = {29493616}, issn = {1476-4687}, mesh = {Biological Evolution ; *Choice Behavior ; Climate Change ; Curriculum ; Florida ; Science/*education ; *State Government ; Teaching/*legislation & jurisprudence ; *Teaching Materials ; Textbooks as Topic ; }, } @article {pmid29493615, year = {2018}, author = {}, title = {Oil and gas emissions could far exceed current estimates.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {5-6}, doi = {10.1038/d41586-018-02581-2}, pmid = {29493615}, issn = {1476-4687}, } @article {pmid29493614, year = {2018}, author = {Greenhill, L}, title = {A surprising chill before the cosmic dawn.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {38-39}, doi = {10.1038/d41586-018-02310-9}, pmid = {29493614}, issn = {1476-4687}, } @article {pmid29493613, year = {2018}, author = {Choi, C}, title = {The mazes with minds of their own.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {127-128}, doi = {10.1038/d41586-018-02403-5}, pmid = {29493613}, issn = {1476-4687}, mesh = {Animals ; Animals, Laboratory ; Attention/physiology ; Automation/economics/*methods ; Behavioral Research/economics/*methods ; Drosophila melanogaster ; Electronic Data Processing/economics/methods ; *Maze Learning ; Memory/physiology ; Mice ; Rats ; Reproducibility of Results ; Video Recording ; Zebrafish ; }, } @article {pmid29493611, year = {2018}, author = {Bai, X and Dawson, RJ and Ürge-Vorsatz, D and Delgado, GC and Salisu Barau, A and Dhakal, S and Dodman, D and Leonardsen, L and Masson-Delmotte, V and Roberts, DC and Schultz, S}, title = {Six research priorities for cities and climate change.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {23-25}, doi = {10.1038/d41586-018-02409-z}, pmid = {29493611}, issn = {1476-4687}, } @article {pmid29493610, year = {2018}, author = {Gibney, E}, title = {UK scientists brace for disruption from huge academic strike.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {14-15}, doi = {10.1038/d41586-018-02350-1}, pmid = {29493610}, issn = {1476-4687}, mesh = {Labor Unions/organization & administration ; Negotiating ; *Pensions ; Research/economics ; *Research Personnel/economics ; *Strikes, Employee/economics ; Students ; Teaching ; United Kingdom ; Universities/*economics ; Workforce ; }, } @article {pmid29493609, year = {2018}, author = {Butler, D}, title = {Researchers have finally created a tool to spot duplicated images across thousands of papers.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {18}, doi = {10.1038/d41586-018-02421-3}, pmid = {29493609}, issn = {1476-4687}, mesh = {*Algorithms ; Automation ; Benchmarking ; Computer Graphics ; *Duplicate Publication as Topic ; Editorial Policies ; Periodicals as Topic/standards ; *Photography ; Plagiarism ; Research Personnel ; Research Report/*standards ; Retraction of Publication as Topic ; Scientific Misconduct/*statistics & numerical data ; *Software ; }, } @article {pmid29493608, year = {2018}, author = {Burioni, R and Odone, A and Signorelli, C}, title = {Lessons from Italy's policy shift on immunization.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {30}, doi = {10.1038/d41586-018-02267-9}, pmid = {29493608}, issn = {1476-4687}, mesh = {*Immunization ; Italy ; *Vaccination ; }, } @article {pmid29493607, year = {2018}, author = {Schaetz, T}, title = {Qubits break the sound barrier.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {33-34}, doi = {10.1038/d41586-018-02402-6}, pmid = {29493607}, issn = {1476-4687}, mesh = {*Sound ; }, } @article {pmid29493606, year = {2018}, author = {Maxmen, A}, title = {Promising HIV vaccines could stall without coordinated research.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {17-18}, doi = {10.1038/d41586-018-02538-5}, pmid = {29493606}, issn = {1476-4687}, mesh = {*AIDS Vaccines ; HIV Infections ; Humans ; Research ; }, } @article {pmid29493605, year = {2018}, author = {Potenza, MN and Higuchi, S and Brand, M}, title = {Call for research into a wider range of behavioural addictions.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {30}, doi = {10.1038/d41586-018-02568-z}, pmid = {29493605}, issn = {1476-4687}, mesh = {*Behavior, Addictive ; *Gambling ; Humans ; Research ; }, } @article {pmid29493604, year = {2018}, author = {Shih, CK and MacDonald, AH}, title = {Quantum upside-down cake.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {36-37}, doi = {10.1038/d41586-018-02329-y}, pmid = {29493604}, issn = {1476-4687}, } @article {pmid29493603, year = {2018}, author = {Gewin, V}, title = {How to write a first-class paper.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {129-130}, doi = {10.1038/d41586-018-02404-4}, pmid = {29493603}, issn = {1476-4687}, } @article {pmid29493602, year = {2018}, author = {}, title = {Corrections.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {18}, doi = {10.1038/d41586-018-02410-6}, pmid = {29493602}, issn = {1476-4687}, } @article {pmid29493601, year = {2018}, author = {Liang, J and O'Brien, LE}, title = {A gut feeling for cellular fate.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {34-36}, doi = {10.1038/d41586-018-01460-0}, pmid = {29493601}, issn = {1476-4687}, mesh = {Biomedical and Dental Materials ; *Cell Differentiation ; Drosophila ; *Gastrointestinal Tract ; }, } @article {pmid29493600, year = {2018}, author = {Berlow, RB and Wright, PE}, title = {Tight complexes from disordered proteins.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {37-38}, doi = {10.1038/d41586-018-01694-y}, pmid = {29493600}, issn = {1476-4687}, mesh = {*Protein Binding ; *Proteins ; Tight Junctions ; }, } @article {pmid29493599, year = {2018}, author = {Linkov, I and Trump, BD and Keisler, J}, title = {Risk and resilience must be independently managed.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {30}, doi = {10.1038/d41586-018-02567-0}, pmid = {29493599}, issn = {1476-4687}, mesh = {Humans ; *Resilience, Psychological ; Risk Management/*methods ; }, } @article {pmid29493598, year = {2018}, author = {Thomson, H}, title = {How flashing lights and pink noise might banish Alzheimer's, improve memory and more.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {20-22}, doi = {10.1038/d41586-018-02391-6}, pmid = {29493598}, issn = {1476-4687}, mesh = {Alzheimer Disease/pathology/physiopathology/*therapy ; Animals ; Biomedical Enhancement/*methods ; Brain Waves/*physiology ; Clinical Trials as Topic ; Cognitive Dysfunction/psychology/therapy ; Female ; Humans ; Memory/*physiology ; Memory Consolidation/physiology ; Mice ; Microglia/immunology/physiology ; Parkinson Disease/physiopathology/*therapy ; Transcranial Direct Current Stimulation ; }, } @article {pmid29493597, year = {2018}, author = {Gewin, V}, title = {Why I won't be silenced on climate resilience.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {131}, doi = {10.1038/d41586-018-02405-3}, pmid = {29493597}, issn = {1476-4687}, } @article {pmid29493596, year = {2018}, author = {}, title = {UK university strike, quark pioneer and the ancient-genome boom.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {10-11}, doi = {10.1038/d41586-018-02389-0}, pmid = {29493596}, issn = {1476-4687}, } @article {pmid29493595, year = {2018}, author = {Schäfer, VM and Ballance, CJ and Thirumalai, K and Stephenson, LJ and Ballance, TG and Steane, AM and Lucas, DM}, title = {Fast quantum logic gates with trapped-ion qubits.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {75-78}, pmid = {29493595}, issn = {1476-4687}, abstract = {Quantum bits (qubits) based on individual trapped atomic ions are a promising technology for building a quantum computer. The elementary operations necessary to do so have been achieved with the required precision for some error-correction schemes. However, the essential two-qubit logic gate that is used to generate quantum entanglement has hitherto always been performed in an adiabatic regime (in which the gate is slow compared with the characteristic motional frequencies of the ions in the trap), resulting in logic speeds of the order of 10 kilohertz. There have been numerous proposals of methods for performing gates faster than this natural 'speed limit' of the trap. Here we implement one such method, which uses amplitude-shaped laser pulses to drive the motion of the ions along trajectories designed so that the gate operation is insensitive to the optical phase of the pulses. This enables fast (megahertz-rate) quantum logic that is robust to fluctuations in the optical phase, which would otherwise be an important source of experimental error. We demonstrate entanglement generation for gate times as short as 480 nanoseconds-less than a single oscillation period of an ion in the trap and eight orders of magnitude shorter than the memory coherence time measured in similar calcium-43 hyperfine qubits. The power of the method is most evident at intermediate timescales, at which it yields a gate error more than ten times lower than can be attained using conventional techniques; for example, we achieve a 1.6-microsecond-duration gate with a fidelity of 99.8 per cent. Faster and higher-fidelity gates are possible at the cost of greater laser intensity. The method requires only a single amplitude-shaped pulse and one pair of beams derived from a continuous-wave laser. It offers the prospect of combining the unrivalled coherence properties, operation fidelities and optical connectivity of trapped-ion qubits with the submicrosecond logic speeds that are usually associated with solid-state devices.}, } @article {pmid29493594, year = {2018}, author = {Shahbazi, MN and Scialdone, A and Skorupska, N and Weberling, A and Recher, G and Zhu, M and Jedrusik, A and Devito, LG and Noli, L and Macaulay, IC and Buecker, C and Khalaf, Y and Ilic, D and Voet, T and Marioni, JC and Zernicka-Goetz, M}, title = {Erratum: Pluripotent state transitions coordinate morphogenesis in mouse and human embryos.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {126}, pmid = {29493594}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24675.}, } @article {pmid29493593, year = {2018}, author = {Kohler, TA and Smith, ME and Bogaard, A and Feinman, GM and Peterson, CE and Betzenhauser, A and Pailes, M and Stone, EC and Prentiss, AM and Dennehy, TJ and Ellyson, LJ and Nicholas, LM and Faulseit, RK and Styring, A and Whitlam, J and Fochesato, M and Foor, TA and Bowles, S}, title = {Corrigendum: Greater post-Neolithic wealth disparities in Eurasia than in North America and Mesoamerica.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {126}, pmid = {29493593}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24646.}, } @article {pmid29493592, year = {2018}, author = {Peters, BJ and Carlson, RW and Day, JMD and Horan, MF}, title = {Hadean silicate differentiation preserved by anomalous 142Nd/144Nd ratios in the Réunion hotspot source.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {89-93}, pmid = {29493592}, issn = {1476-4687}, abstract = {Active volcanic hotspots can tap into domains in Earth's deep interior that were formed more than two billion years ago. High-precision data on variability in tungsten isotopes have shown that some of these domains resulted from differentiation events that occurred within the first fifty million years of Earth history. However, it has not proved easy to resolve analogous variability in neodymium isotope compositions that would track regions of Earth's interior whose composition was established by events occurring within roughly the first five hundred million years of Earth history. Here we report 142Nd/144Nd ratios for Réunion Island igneous rocks, some of which are resolvably either higher or lower than the ratios in modern upper-mantle domains. We also find that Réunion 142Nd/144Nd ratios correlate with helium-isotope ratios (3He/4He), suggesting parallel behaviour of these isotopic systems during very early silicate differentiation, perhaps as early as 4.39 billion years ago. The range of 142Nd/144Nd ratios in Réunion basalts is inconsistent with a single-stage differentiation process, and instead requires mixing of a conjugate melt and residue formed in at least one melting event during the Hadean eon, 4.56 billion to 4 billion years ago. Efficient post-Hadean mixing nearly erased the ancient, anomalous 142Nd/144Nd signatures, and produced the relatively homogeneous 143Nd/144Nd composition that is characteristic of Réunion basalts. Our results show that Réunion magmas tap into a particularly ancient, primitive source compared with other volcanic hotspots, offering insight into the formation and preservation of ancient heterogeneities in Earth's interior.}, } @article {pmid29493591, year = {2018}, author = {Osgood-Zimmerman, A and Millear, AI and Stubbs, RW and Shields, C and Pickering, BV and Earl, L and Graetz, N and Kinyoki, DK and Ray, SE and Bhatt, S and Browne, AJ and Burstein, R and Cameron, E and Casey, DC and Deshpande, A and Fullman, N and Gething, PW and Gibson, HS and Henry, NJ and Herrero, M and Krause, LK and Letourneau, ID and Levine, AJ and Liu, PY and Longbottom, J and Mayala, BK and Mosser, JF and Noor, AM and Pigott, DM and Piwoz, EG and Rao, P and Rawat, R and Reiner, RC and Smith, DL and Weiss, DJ and Wiens, KE and Mokdad, AH and Lim, SS and Murray, CJL and Kassebaum, NJ and Hay, SI}, title = {Mapping child growth failure in Africa between 2000 and 2015.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {41-47}, pmid = {29493591}, issn = {1476-4687}, mesh = {Africa/epidemiology ; *Child Development ; Child, Preschool ; Female ; Goals ; *Growth ; Growth Disorders/*epidemiology/prevention & control ; Humans ; Infant ; Infant, Newborn ; Male ; Malnutrition/*epidemiology/prevention & control ; Prevalence ; Public Health/statistics & numerical data ; Thinness/epidemiology/prevention & control ; Wasting Syndrome/*epidemiology/prevention & control ; World Health Organization ; }, abstract = {Insufficient growth during childhood is associated with poor health outcomes and an increased risk of death. Between 2000 and 2015, nearly all African countries demonstrated improvements for children under 5 years old for stunting, wasting, and underweight, the core components of child growth failure. Here we show that striking subnational heterogeneity in levels and trends of child growth remains. If current rates of progress are sustained, many areas of Africa will meet the World Health Organization Global Targets 2025 to improve maternal, infant and young child nutrition, but high levels of growth failure will persist across the Sahel. At these rates, much, if not all of the continent will fail to meet the Sustainable Development Goal target-to end malnutrition by 2030. Geospatial estimates of child growth failure provide a baseline for measuring progress as well as a precision public health platform to target interventions to those populations with the greatest need, in order to reduce health disparities and accelerate progress.}, } @article {pmid29493590, year = {2018}, author = {Barkana, R}, title = {Possible interaction between baryons and dark-matter particles revealed by the first stars.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {71-74}, pmid = {29493590}, issn = {1476-4687}, abstract = {The cosmic radio-frequency spectrum is expected to show a strong absorption signal corresponding to the 21-centimetre-wavelength transition of atomic hydrogen around redshift 20, which arises from Lyman-α radiation from some of the earliest stars. By observing this 21-centimetre signal-either its sky-averaged spectrum or maps of its fluctuations, obtained using radio interferometers-we can obtain information about cosmic dawn, the era when the first astrophysical sources of light were formed. The recent detection of the global 21-centimetre spectrum reveals a stronger absorption than the maximum predicted by existing models, at a confidence level of 3.8 standard deviations. Here we report that this absorption can be explained by the combination of radiation from the first stars and excess cooling of the cosmic gas induced by its interaction with dark matter. Our analysis indicates that the spatial fluctuations of the 21-centimetre signal at cosmic dawn could be an order of magnitude larger than previously expected and that the dark-matter particle is no heavier than several proton masses, well below the commonly predicted mass of weakly interacting massive particles. Our analysis also confirms that dark matter is highly non-relativistic and at least moderately cold, and primordial velocities predicted by models of warm dark matter are potentially detectable. These results indicate that 21-centimetre cosmology can be used as a dark-matter probe.}, } @article {pmid29493589, year = {2018}, author = {Whiteley, M and Diggle, SP and Greenberg, EP}, title = {Corrigendum: Progress in and promise of bacterial quorum sensing research.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {126}, pmid = {29493589}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24624.}, } @article {pmid29493588, year = {2018}, author = {Graetz, N and Friedman, J and Osgood-Zimmerman, A and Burstein, R and Biehl, MH and Shields, C and Mosser, JF and Casey, DC and Deshpande, A and Earl, L and Reiner, RC and Ray, SE and Fullman, N and Levine, AJ and Stubbs, RW and Mayala, BK and Longbottom, J and Browne, AJ and Bhatt, S and Weiss, DJ and Gething, PW and Mokdad, AH and Lim, SS and Murray, CJL and Gakidou, E and Hay, SI}, title = {Mapping local variation in educational attainment across Africa.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {48-53}, pmid = {29493588}, issn = {1476-4687}, mesh = {Adolescent ; Adult ; Africa ; *Educational Status ; Female ; Goals ; Humans ; Internationality ; Male ; Middle Aged ; Probability ; Sex Factors ; World Health Organization ; Young Adult ; }, abstract = {Educational attainment for women of reproductive age is linked to reduced child and maternal mortality, lower fertility and improved reproductive health. Comparable analyses of attainment exist only at the national level, potentially obscuring patterns in subnational inequality. Evidence suggests that wide disparities between urban and rural populations exist, raising questions about where the majority of progress towards the education targets of the Sustainable Development Goals is occurring in African countries. Here we explore within-country inequalities by predicting years of schooling across five by five kilometre grids, generating estimates of average educational attainment by age and sex at subnational levels. Despite marked progress in attainment from 2000 to 2015 across Africa, substantial differences persist between locations and sexes. These differences have widened in many countries, particularly across the Sahel. These high-resolution, comparable estimates improve the ability of decision-makers to plan the precisely targeted interventions that will be necessary to deliver progress during the era of the Sustainable Development Goals.}, } @article {pmid29493587, year = {2018}, author = {Bowman, JD and Rogers, AEE and Monsalve, RA and Mozdzen, TJ and Mahesh, N}, title = {An absorption profile centred at 78 megahertz in the sky-averaged spectrum.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {67-70}, pmid = {29493587}, issn = {1476-4687}, abstract = {After stars formed in the early Universe, their ultraviolet light is expected, eventually, to have penetrated the primordial hydrogen gas and altered the excitation state of its 21-centimetre hyperfine line. This alteration would cause the gas to absorb photons from the cosmic microwave background, producing a spectral distortion that should be observable today at radio frequencies of less than 200 megahertz. Here we report the detection of a flattened absorption profile in the sky-averaged radio spectrum, which is centred at a frequency of 78 megahertz and has a best-fitting full-width at half-maximum of 19 megahertz and an amplitude of 0.5 kelvin. The profile is largely consistent with expectations for the 21-centimetre signal induced by early stars; however, the best-fitting amplitude of the profile is more than a factor of two greater than the largest predictions. This discrepancy suggests that either the primordial gas was much colder than expected or the background radiation temperature was hotter than expected. Astrophysical phenomena (such as radiation from stars and stellar remnants) are unlikely to account for this discrepancy; of the proposed extensions to the standard model of cosmology and particle physics, only cooling of the gas as a result of interactions between dark matter and baryons seems to explain the observed amplitude. The low-frequency edge of the observed profile indicates that stars existed and had produced a background of Lyman-α photons by 180 million years after the Big Bang. The high-frequency edge indicates that the gas was heated to above the radiation temperature less than 100 million years later.}, } @article {pmid29493490, year = {2018}, author = {Boden, R and Scott, KM and Rae, AW and Hutt, LP}, title = {Corrigendum: Reclassification of Thiomicrospira hydrogeniphila (Watsuji et al. 2016) to Thiomicrorhabdus hydrogenophila comb. nov., with emended description of Thiomicrorhabdus (Boden et al., 2017).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {975}, doi = {10.1099/ijsem.0.002627}, pmid = {29493490}, issn = {1466-5034}, } @article {pmid29493487, year = {2018}, author = {Chuah, LO and Yap, KP and Shamila-Syuhada, AK and Thong, KL and Ahmad, R and Liong, MT and Rusul, G}, title = {Corrigendum: Floricoccus tropicus gen. nov., sp. nov. and Floricoccus penangensis sp. nov. isolated from fresh flowers of durian tree and hibiscus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {974}, doi = {10.1099/ijsem.0.002582}, pmid = {29493487}, issn = {1466-5034}, } @article {pmid29493486, year = {2018}, author = {Oren, A and Garrity, GM}, title = {List of new names and new combinations previously effectively, but not validly, published.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {693-694}, doi = {10.1099/ijsem.0.002570}, pmid = {29493486}, issn = {1466-5034}, } @article {pmid29493485, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 67, part 12, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {695-697}, doi = {10.1099/ijsem.0.002546}, pmid = {29493485}, issn = {1466-5034}, } @article {pmid29493067, year = {2018}, author = {Cheng, X and Zheng, J and Li, G and Göbel, V and Zhang, H}, title = {Degradation for better survival? Role of ubiquitination in epithelial morphogenesis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1438-1460}, doi = {10.1111/brv.12404}, pmid = {29493067}, issn = {1469-185X}, abstract = {As a prevalent post-translational modification, ubiquitination is essential for many developmental processes. Once covalently attached to the small and conserved polypeptide ubiquitin (Ub), a substrate protein can be directed to perform specific biological functions via its Ub-modified form. Three sequential catalytic reactions contribute to this process, among which E3 ligases serve to identify target substrates and promote the activated Ub to conjugate to substrate proteins. Ubiquitination has great plasticity, with diverse numbers, topologies and modifications of Ub chains conjugated at different substrate residues adding a layer of complexity that facilitates a huge range of cellular functions. Herein, we highlight key advances in the understanding of ubiquitination in epithelial morphogenesis, with an emphasis on the latest insights into its roles in cellular events involved in polarized epithelial tissue, including cell adhesion, asymmetric localization of polarity determinants and cytoskeletal organization. In addition, the physiological roles of ubiquitination are discussed for typical examples of epithelial morphogenesis, such as lung branching, vascular development and synaptic formation and plasticity. Our increased understanding of ubiquitination in epithelial morphogenesis may provide novel insights into the molecular mechanisms underlying epithelial regeneration and maintenance.}, } @article {pmid29492778, year = {2018}, author = {Larsen, PA}, title = {Transposable elements and the multidimensional genome.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {1-2}, pages = {1-3}, pmid = {29492778}, issn = {1573-6849}, mesh = {DNA Transposable Elements/*genetics ; Epigenomics ; Genome/*genetics ; Genomics/methods ; }, } @article {pmid29492649, year = {2018}, author = {Wani, ZA and Ahmad, T and Nalli, Y and Ali, A and Singh, AP and Vishwakarma, RA and Ashraf, N and Riyaz-Ul-Hassan, S}, title = {Porostereum sp., Associated with Saffron (Crocus sativus L.), is a Latent Pathogen Capable of Producing Phytotoxic Chlorinated Aromatic Compounds.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {880-887}, pmid = {29492649}, issn = {1432-0991}, mesh = {Arabidopsis/drug effects ; Crocus/*microbiology ; Herbicides/*metabolism/pharmacology ; Hydrocarbons, Aromatic/*metabolism/pharmacology ; Hydrocarbons, Chlorinated/*metabolism/pharmacology ; Phylogeny ; Plant Diseases/*microbiology ; Polyporales/*chemistry/genetics/*isolation & purification/metabolism ; }, abstract = {Saffron (Crocus sativus L.) is one of the most expensive spices in the world due to its medicinal and aromatic value. However, saffron production is severely affected by the corm rot disease throughout the saffron producing countries. In this study, we report a basidiomycetous latent pathogen of saffron, designated as CSE26, capable of producing phytotoxic compounds. CSE26 is a highly odorous basidiomycete with monomitic hyphal system. Molecular phylogeny of ITS and 28S ribosomal gene sequence of CSE26 assigned it as Porostereum spadiceum. It was found to produce corm rot in C. sativus under in vivo and field conditions, with a disease severity index of 0.7 and 0.5, respectively. CSE26 was found to produce chlorinated aromatic compounds (CAMs) having phytotoxic activity against Arabidopsis plants. Therefore, these compounds may be acting as pathogenic determinants of CSE26. However, there is a need to study the level of production of these CAMs by this fungus in the natural environment and their effects on plant health.}, } @article {pmid29492266, year = {2018}, author = {Bove, RM}, title = {Why monkeys do not get multiple sclerosis (spontaneously): An evolutionary approach.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {43-59}, pmid = {29492266}, issn = {2050-6201}, abstract = {The goal of this review is to apply an evolutionary lens to understanding the origins of multiple sclerosis (MS), integrating three broad observations. First, only humans are known to develop MS spontaneously. Second, humans have evolved large brains, with characteristically large amounts of metabolically costly myelin. This myelin is generated over long periods of neurologic development-and peak MS onset coincides with the end of myelination. Third, over the past century there has been a disproportionate increase in the rate of MS in young women of childbearing age, paralleling increasing westernization and urbanization, indicating sexually specific susceptibility in response to changing exposures. From these three observations about MS, a life history approach leads us to hypothesize that MS arises in humans from disruption of the normal homeostatic mechanisms of myelin production and maintenance, during our uniquely long myelination period. This review will highlight under-explored areas of homeostasis in brain development, that are likely to shed new light on the origins of MS and to raise further questions about the interactions between our ancestral genes and modern environments.}, } @article {pmid29492265, year = {2018}, author = {White, C and Fessler, DMT}, title = {An evolutionary account of vigilance in grief.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {34-42}, pmid = {29492265}, issn = {2050-6201}, abstract = {Grief is characterized by a number of cardinal cognitive symptoms, including preoccupation with thoughts of the deceased and vigilance toward indications that the deceased is in the environment. Compared with emotional symptoms, little attention has been paid to the ultimate function of vigilance in grief. Drawing on signal-detection theory, we propose that the ultimate function of vigilance is to facilitate the reunification (where possible) with a viable relationship partner following separation. Preoccupation with thoughts about the missing person creates the cognitive conditions necessary to maintain a low baseline threshold for the detection of the agent-any information associated with the agent is highly salient, and attention is correspondingly readily deployed toward such cues. These patterns are adaptive in cases of an absent but living partner, but maladaptive in cases of the death of a partner. That they occur in the latter likely reflects the intersection of error-management considerations and the kludge-like configuration of the mind. We discuss results from two previous studies designed to test predictions concerning input conditions and individual differences based on this account, and consider the implications of these findings for mainstream bereavement theories and practices.}, } @article {pmid29492264, year = {2018}, author = {Enam, SF and Hashmi, S}, title = {The importance of Evolutionary Medicine in developing countries: A case for Pakistan's medical schools.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {26-33}, pmid = {29492264}, issn = {2050-6201}, abstract = {Evolutionary Medicine (EM) is a fundamental science exploring why our bodies are plagued with disease and hindered by limitations. EM views the body as an assortment of benefits, mistakes, and compromises molded over millennia. It highlights the role of evolution in numerous diseases encountered in community and family medicine clinics of developing countries. It enables us to ask informed questions and develop novel responses to global health problems. An understanding of the field is thus crucial for budding doctors, but its study is currently limited to a handful of medical schools in high-income countries. For the developing world, Pakistan's medical schools may be excellent starting posts as the country is beset with communicable and non-communicable diseases that are shaped by evolution. Remarkably, Pakistani medical students are open to studying and incorporating EM into their training. Understanding the principles of EM could empower them to tackle growing health problems in the country. Additionally, some difficulties that western medical schools face in integrating EM into their curriculum may not be a hindrance in Pakistan. We propose solutions for the remaining challenges, including obstinate religious sentiments. Herein, we make the case that incorporating EM is particularly important in developing countries such as Pakistan and that it is achievable in its medical student body.}, } @article {pmid29492263, year = {2018}, author = {Nunn, CL}, title = {A roadmap for 'core concepts' in evolutionary medicine.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {24-25}, pmid = {29492263}, issn = {2050-6201}, } @article {pmid29490920, year = {2018}, author = {Rempe, DM and Dietrich, WE}, title = {Direct observations of rock moisture, a hidden component of the hydrologic cycle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2664-2669}, pmid = {29490920}, issn = {1091-6490}, abstract = {Recent theory and field observations suggest that a systematically varying weathering zone, that can be tens of meters thick, commonly develops in the bedrock underlying hillslopes. Weathering turns otherwise poorly conductive bedrock into a dynamic water storage reservoir. Infiltrating precipitation typically will pass through unsaturated weathered bedrock before reaching groundwater and running off to streams. This invisible and difficult to access unsaturated zone is virtually unexplored compared with the surface soil mantle. We have proposed the term "rock moisture" to describe the exchangeable water stored in the unsaturated zone in weathered bedrock, purposely choosing a term parallel to, but distinct from, soil moisture, because weathered bedrock is a distinctly different material that is distributed across landscapes independently of soil thickness. Here, we report a multiyear intensive campaign of quantifying rock moisture across a hillslope underlain by a thick weathered bedrock zone using repeat neutron probe measurements in a suite of boreholes. Rock moisture storage accumulates in the wet season, reaches a characteristic upper value, and rapidly passes any additional rainfall downward to groundwater. Hence, rock moisture storage mediates the initiation and magnitude of recharge and runoff. In the dry season, rock moisture storage is gradually depleted by trees for transpiration, leading to a common lower value at the end of the dry season. Up to 27% of the annual rainfall is seasonally stored as rock moisture. Significant rock moisture storage is likely common, and yet it is missing from hydrologic and land-surface models used to predict regional and global climate.}, } @article {pmid29490919, year = {2018}, author = {Brammer, DW and Gillespie, PJ and Tian, M and Young, D and Raveendran, M and Williams, LE and Gagea, M and Benavides, FJ and Perez, CJ and Broaddus, RR and Bernacky, BJ and Barnhart, KF and Alauddin, MM and Bhutani, MS and Gibbs, RA and Sidman, RL and Pasqualini, R and Arap, W and Rogers, J and Abee, CR and Gelovani, JG}, title = {MLH1-rheMac hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2806-2811}, pmid = {29490919}, issn = {1091-6490}, mesh = {Animals ; Colorectal Neoplasms, Hereditary Nonpolyposis/diagnostic imaging/genetics/metabolism/*veterinary ; Female ; *Macaca mulatta/genetics/metabolism ; Male ; Microsatellite Instability ; MutL Protein Homolog 1/genetics/*metabolism ; Polymorphism, Single Nucleotide ; Positron Emission Tomography Computed Tomography ; Primate Diseases/diagnostic imaging/genetics/*metabolism/pathology ; }, abstract = {Over the past two decades, 33 cases of colonic adenocarcinomas have been diagnosed in rhesus macaques (Macaca mulatta) at the nonhuman primate colony of the Keeling Center for Comparative Medicine and Research at The University of Texas MD Anderson Cancer Center. The distinctive feature in these cases, based on PET/computed tomography (CT) imaging, was the presence of two or three tumor lesions in different locations, including proximal to the ileocecal juncture, proximal to the hepatic flexure, and/or in the sigmoid colon. These colon carcinoma lesions selectively accumulated [18F]fluorodeoxyglucose ([18F]FDG) and [18F]fluoroacetate ([18F]FACE) at high levels, reflecting elevated carbohydrate and fatty acid metabolism in these tumors. In contrast, the accumulation of [18F]fluorothymidine ([18F]FLT) was less significant, reflecting slow proliferative activity in these tumors. The diagnoses of colon carcinomas were confirmed by endoscopy. The expression of MLH1, MSH2, and MSH6 proteins and the degree of microsatellite instability (MSI) was assessed in colon carcinomas. The loss of MLH1 protein expression was observed in all tumors and was associated with a deletion mutation in the MLH1 promoter region and/or multiple single-nucleotide polymorphism (SNP) mutations in the MLH1 gene. All tumors exhibited various degrees of MSI. The pedigree analysis of this rhesus macaque population revealed several clusters of affected animals related to each other over several generations, suggesting an autosomal dominant transmission of susceptibility for colon cancer. The newly discovered hereditary nonpolyposis colorectal cancer syndrome in rhesus macaques, termed MLH1-rheMac, may serve as a model for development of novel approaches to diagnosis and therapy of Lynch syndrome in humans.}, } @article {pmid29490918, year = {2018}, author = {Vergara-Temprado, J and Miltenberger, AK and Furtado, K and Grosvenor, DP and Shipway, BJ and Hill, AA and Wilkinson, JM and Field, PR and Murray, BJ and Carslaw, KS}, title = {Strong control of Southern Ocean cloud reflectivity by ice-nucleating particles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2687-2692}, pmid = {29490918}, issn = {1091-6490}, abstract = {Large biases in climate model simulations of cloud radiative properties over the Southern Ocean cause large errors in modeled sea surface temperatures, atmospheric circulation, and climate sensitivity. Here, we combine cloud-resolving model simulations with estimates of the concentration of ice-nucleating particles in this region to show that our simulated Southern Ocean clouds reflect far more radiation than predicted by global models, in agreement with satellite observations. Specifically, we show that the clouds that are most sensitive to the concentration of ice-nucleating particles are low-level mixed-phase clouds in the cold sectors of extratropical cyclones, which have previously been identified as a main contributor to the Southern Ocean radiation bias. The very low ice-nucleating particle concentrations that prevail over the Southern Ocean strongly suppress cloud droplet freezing, reduce precipitation, and enhance cloud reflectivity. The results help explain why a strong radiation bias occurs mainly in this remote region away from major sources of ice-nucleating particles. The results present a substantial challenge to climate models to be able to simulate realistic ice-nucleating particle concentrations and their effects under specific meteorological conditions.}, } @article {pmid29490707, year = {2018}, author = {Al-Dwibe, H and Amro, A and Gashout, A and El-Zurghany, A and El-Zubi, S and El-Hashme, M and Hamarsheh, O and Maree, M}, title = {A pyoderma gangrenous-like cutaneous leishmaniasis in a Libyan woman with rheumatoid arthritis: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {158}, pmid = {29490707}, issn = {1756-0500}, mesh = {*Arthritis, Rheumatoid ; Female ; Humans ; Leishmaniasis, Cutaneous/*diagnosis ; Libya ; Middle Aged ; Pyoderma Gangrenosum/*diagnosis ; }, abstract = {BACKGROUND: Several case reports describe diseases presenting with skin ulcerations, which resemble pyoderma gangrenosum especially in immune-compromised patients, often proven on further workup, to have an infective or malignant etiology. However, treatment of pyoderma gangrenosum by systemic steroids or other immunosuppressive agents may worsen the condition.

CASE PRESENTATION: We report here, a 45 year-old Libyan woman with rheumatoid arthritis on low dose steroids with pyoderma gangrenosum-like skin lesions and positive pathergy. Slit-smear was positive for Leishmania amastigotes and histopathological examination confirmed the diagnosis of cutaneous leishmaniasis. The lesions healed completely by parenteral sodium stibogluconate (Pentostam) 600 mg daily.

CONCLUSION: We report for the first time, a rare and unusual presentation of pyoderma gangrenosum like-cutaneous leishmaniasis in a patient with rheumatoid arthritis. Atypical cutaneous leishmaniasis should not be ruled out in the differential diagnosis of unresponsive skin diseases, with slit/smear and a skin biopsy is required.}, } @article {pmid29490697, year = {2018}, author = {Naas, AE and Solden, LM and Norbeck, AD and Brewer, H and Hagen, LH and Heggenes, IM and McHardy, AC and Mackie, RI and Paša-Tolić, L and Arntzen, MØ and Eijsink, VGH and Koropatkin, NM and Hess, M and Wrighton, KC and Pope, PB}, title = {"Candidatus Paraporphyromonas polyenzymogenes" encodes multi-modular cellulases linked to the type IX secretion system.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {44}, pmid = {29490697}, issn = {2049-2618}, support = {250479//Norges Forskningsråd/International ; 336355//H2020 European Research Council/International ; }, mesh = {Animals ; Bacterial Secretion Systems/*genetics ; Bacteroidetes/*classification/*enzymology/genetics ; Carbohydrate Metabolism/*physiology ; Cattle ; Cellulases/*genetics/metabolism ; Gastrointestinal Microbiome/*genetics ; Lignin/*metabolism ; Plants/metabolism ; Rumen/metabolism/microbiology ; Sheep ; }, abstract = {BACKGROUND: In nature, obligate herbivorous ruminants have a close symbiotic relationship with their gastrointestinal microbiome, which proficiently deconstructs plant biomass. Despite decades of research, lignocellulose degradation in the rumen has thus far been attributed to a limited number of culturable microorganisms. Here, we combine meta-omics and enzymology to identify and describe a novel Bacteroidetes family ("Candidatus MH11") composed entirely of uncultivated strains that are predominant in ruminants and only distantly related to previously characterized taxa.

RESULTS: The first metabolic reconstruction of Ca. MH11-affiliated genome bins, with a particular focus on the provisionally named "Candidatus Paraporphyromonas polyenzymogenes", illustrated their capacity to degrade various lignocellulosic substrates via comprehensive inventories of singular and multi-modular carbohydrate active enzymes (CAZymes). Closer examination revealed an absence of archetypical polysaccharide utilization loci found in human gut microbiota. Instead, we identified many multi-modular CAZymes putatively secreted via the Bacteroidetes-specific type IX secretion system (T9SS). This included cellulases with two or more catalytic domains, which are modular arrangements that are unique to Bacteroidetes species studied to date. Core metabolic proteins from Ca. P. polyenzymogenes were detected in metaproteomic data and were enriched in rumen-incubated plant biomass, indicating that active saccharification and fermentation of complex carbohydrates could be assigned to members of this novel family. Biochemical analysis of selected Ca. P. polyenzymogenes CAZymes further iterated the cellulolytic activity of this hitherto uncultured bacterium towards linear polymers, such as amorphous and crystalline cellulose as well as mixed linkage β-glucans.

CONCLUSION: We propose that Ca. P. polyenzymogene genotypes and other Ca. MH11 members actively degrade plant biomass in the rumen of cows, sheep and most likely other ruminants, utilizing singular and multi-domain catalytic CAZymes secreted through the T9SS. The discovery of a prominent role of multi-modular cellulases in the Gram-negative Bacteroidetes, together with similar findings for Gram-positive cellulosomal bacteria (Ruminococcus flavefaciens) and anaerobic fungi (Orpinomyces sp.), suggests that complex enzymes are essential and have evolved within all major cellulolytic dominions inherent to the rumen.}, } @article {pmid29490684, year = {2018}, author = {Levy, J and Tamborindeguy, C and Athrey, G and Scheuring, DC and Koym, JW and Miller, JC}, title = {Transcriptome of Russet Norkotah and its clonal selection, TXNS278.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {160}, doi = {10.1186/s13104-018-3254-4}, pmid = {29490684}, issn = {1756-0500}, mesh = {Genome, Plant/*genetics ; Plant Leaves/genetics ; Plant Tubers/*genetics ; Sequence Analysis, RNA ; Solanum tuberosum/*genetics ; Transcriptome/*genetics ; }, abstract = {OBJECTIVES: Potato has a large genetic diversity. This diversity is in part due to somaclonal variability that appears within potato selections for which tubers are used as seeds. However, the potato tetraploid genome, as well as the use of tubers for crop propagation, does not allow for easy genetic studies. The objective is to gain knowledge at the genomic level from standard Russet Norkotah and a subclonal Russet Norkotah selection TXNS278.

DATA DESCRIPTION: In this report, we used RNA-seq, which allows genome-wide gene expression analysis to sequence the transcriptomes of the subclonal Russet Norkotah selection TXNS278 with standard Russet Norkotah grown in commercial fields. Among the selections, TXNS278 appeared in a multi-year analysis in Texas as a top No 1 yielding variety. Russet Norkotah and TXNS278 leaf and root transcriptomes were sequenced at two time points during growing season.}, } @article {pmid29490667, year = {2018}, author = {Folayan, MO and Haire, B and Allman, D and Yakubu, A and Afolabi, MO}, title = {Research priorities during infectious disease emergencies in West Africa.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {159}, pmid = {29490667}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; 202969/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {*Biomedical Research ; *Clinical Trials as Topic ; *Communicable Disease Control ; Communicable Diseases/*transmission ; Delphi Technique ; Disease Outbreaks/*prevention & control ; Emergencies ; Humans ; *Research Design ; }, abstract = {OBJECTIVES: This paper presents the results of the consultations conducted with various stakeholders in Africa and other experts to document community perspectives on the types of research to be prioritised in outbreak conditions. The Delphi method was used to distill consensus.

RESULTS: Our consultations highlighted as key, the notion that in an infectious disease outbreak situation, the need to establish an evidence base on how to reduce morbidity and mortality in real time takes precedence over the production of generalizable knowledge. Research studies that foster understanding of how disease transmission could be prevented in the future remain important, implementation research that explores how to mitigate the impact of outbreaks in the present should be prioritized. Clinical trials aiming to establish the safety profile of therapeutic interventions should be limited during the acute phase of an epidemic with high fatality-and should preferably use adaptive designs. We concluded that community members have valuable perspectives to share about research priorities during infectious disease emergencies. Well designed consultative processes could help identify these opinions.}, } @article {pmid29490630, year = {2018}, author = {Ou, J and Liu, H and Yu, J and Kelliher, MA and Castilla, LH and Lawson, ND and Zhu, LJ}, title = {ATACseqQC: a Bioconductor package for post-alignment quality assessment of ATAC-seq data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {169}, pmid = {29490630}, issn = {1471-2164}, mesh = {Binding Sites ; Computational Biology/*methods ; DNA Transposable Elements ; DNA-Binding Proteins ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Mutagenesis, Insertional ; Sequence Analysis, DNA/*methods ; *Software ; Transcription Initiation Site ; Transposases/genetics/metabolism ; Web Browser ; }, abstract = {BACKGROUND: ATAC-seq (Assays for Transposase-Accessible Chromatin using sequencing) is a recently developed technique for genome-wide analysis of chromatin accessibility. Compared to earlier methods for assaying chromatin accessibility, ATAC-seq is faster and easier to perform, does not require cross-linking, has higher signal to noise ratio, and can be performed on small cell numbers. However, to ensure a successful ATAC-seq experiment, step-by-step quality assurance processes, including both wet lab quality control and in silico quality assessment, are essential. While several tools have been developed or adopted for assessing read quality, identifying nucleosome occupancy and accessible regions from ATAC-seq data, none of the tools provide a comprehensive set of functionalities for preprocessing and quality assessment of aligned ATAC-seq datasets.

RESULTS: We have developed a Bioconductor package, ATACseqQC, for easily generating various diagnostic plots to help researchers quickly assess the quality of their ATAC-seq data. In addition, this package contains functions to preprocess aligned ATAC-seq data for subsequent peak calling. Here we demonstrate the utilities of our package using 25 publicly available ATAC-seq datasets from four studies. We also provide guidelines on what the diagnostic plots should look like for an ideal ATAC-seq dataset.

CONCLUSIONS: This software package has been used successfully for preprocessing and assessing several in-house and public ATAC-seq datasets. Diagnostic plots generated by this package will facilitate the quality assessment of ATAC-seq data, and help researchers to evaluate their own ATAC-seq experiments as well as select high-quality ATAC-seq datasets from public repositories such as GEO to avoid generating hypotheses or drawing conclusions from low-quality ATAC-seq experiments. The software, source code, and documentation are freely available as a Bioconductor package at https://bioconductor.org/packages/release/bioc/html/ATACseqQC.html .}, } @article {pmid29490628, year = {2018}, author = {Klich, A and Mercier, C and Gerfault, L and Grangeat, P and Beaulieu, C and Degout-Charmette, E and Fortin, T and Mahé, P and Giovannelli, JF and Charrier, JP and Giremus, A and Maucort-Boulch, D and Roy, P}, title = {Variance component analysis to assess protein quantification in biomarker validation: application to selected reaction monitoring-mass spectrometry.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {73}, pmid = {29490628}, issn = {1471-2105}, support = {BLAN 0313//Agence Nationale de la Recherche/International ; }, mesh = {*Algorithms ; Analysis of Variance ; Biomarkers/*analysis ; Enzyme-Linked Immunosorbent Assay ; Humans ; *Mass Spectrometry ; Proteins/*analysis ; Reproducibility of Results ; }, abstract = {BACKGROUND: In the field of biomarker validation with mass spectrometry, controlling the technical variability is a critical issue. In selected reaction monitoring (SRM) measurements, this issue provides the opportunity of using variance component analysis to distinguish various sources of variability. However, in case of unbalanced data (unequal number of observations in all factor combinations), the classical methods cannot correctly estimate the various sources of variability, particularly in presence of interaction. The present paper proposes an extension of the variance component analysis to estimate the various components of the variance, including an interaction component in case of unbalanced data.

RESULTS: We applied an experimental design that uses a serial dilution to generate known relative protein concentrations and estimated these concentrations by two processing algorithms, a classical and a more recent one. The extended method allowed estimating the variances explained by the dilution and the technical process by each algorithm in an experiment with 9 proteins: L-FABP, 14.3.3 sigma, Calgi, Def.A6, Villin, Calmo, I-FABP, Peroxi-5, and S100A14. Whereas, the recent algorithm gave a higher dilution variance and a lower technical variance than the classical one in two proteins with three peptides (L-FABP and Villin), there were no significant difference between the two algorithms on all proteins.

CONCLUSIONS: The extension of the variance component analysis was able to estimate correctly the variance components of protein concentration measurement in case of unbalanced design.}, } @article {pmid29490615, year = {2018}, author = {Huang, KC and Lin, WC and Cheng, WH}, title = {Salt hypersensitive mutant 9, a nucleolar APUM23 protein, is essential for salt sensitivity in association with the ABA signaling pathway in Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {40}, pmid = {29490615}, issn = {1471-2229}, support = {MOST 103-2321-B-001-014//the Ministry of Science and Technology (MOST)/ ; }, mesh = {Abscisic Acid/*metabolism ; Arabidopsis/drug effects/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Gene Expression Regulation, Plant ; Plants, Genetically Modified/drug effects/genetics/metabolism ; Proteomics/methods ; RNA-Binding Proteins/genetics/*metabolism ; Signal Transduction/drug effects ; }, abstract = {BACKGROUND: Although the nucleolus involves two major functions: pre-rRNA processing and ribosome biogenesis/assembly, increasing evidence indicates that it also plays important roles in response to abiotic stress. However, the possible regulatory mechanisms underlying the nucleolar proteins responsive to abiotic stress are largely unknown. High salinity is one of the major abiotic stresses, which hinders plant growth and productivity. Here, genetic screening approach was used to identify a salt hypersensitive mutant 9 (sahy9) mutant, also known as apum23, in Arabidopsis thaliana. Functional characterization of SAHY9/APUM23 through analyses of gene/protein expression profiles and metabolites was performed to decipher the possible regulatory mechanisms of the nucleolar protein SAHY9/APUM23 in response to salt stress.

RESULTS: Seedlings of the sahy9/apum23 mutant displayed postgermination developmental arrest and then became bleached after prolonged culture under various salt stresses. Transcriptomic and proteomic analyses of salt-treated sahy9/apum23 and wild-type seedlings revealed differential expression of genes/proteins that have similar functional categories of biological processes, primarily those involved in cellular and metabolic processes as well as abiotic and biotic stress responses. However, the consistency of differential gene expression at both the transcript and protein levels was low (~ 12%), which suggests the involvement of posttranscriptional processing during the salt response. Furthermore, the altered expression of genes and proteins mediated by SAHY9/APUM23 regarding salt sensitivity involves abscisic acid (ABA) biosynthesis and signaling, abiotic stress responses, and ribosome biogenesis-related genes. Importantly, NCED3, ABI2, PP2CA, and major ABA-responsive marker genes, such as RD20 and RD29B, were down-regulated at both the transcript and protein levels in conjunction with lower contents of ABA and changes in the expression of a subset of LEA proteins in sahy9/apum23 mutants under salt stress. Moreover, the salt hypersensitivity of the sahy9/apum23 mutant was largely rescued by the exogenous application of ABA during salt stress.

CONCLUSION: Our results revealed that SAHY9/APUM23 regulated the expression of ribosome biogenesis-related genes and proteins, which further affected the ribosome composition and abundance, and potential posttranscriptional regulation. The salt hypersensitivity of sahy9/apum23 is associated with the ABA-mediated signaling pathway and the downstream stress-responsive network of this pathway.}, } @article {pmid29490613, year = {2018}, author = {Zhang, X and Liu, X and Liu, C and Wei, J and Yu, H and Dong, B}, title = {Identification and characterization of microRNAs involved in ascidian larval metamorphosis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {168}, pmid = {29490613}, issn = {1471-2164}, support = {31572352//National Natural Science Foundation of China/International ; 31771649//National Natural Science Foundation of China/International ; 41706153//National Natural Science Foundation of China/International ; QNLM2016ORP0301//Qingdao National Laboratory for Marine Science and Technology/International ; 201502035//Taishan Scholar Program of Shandong Province, China/International ; }, mesh = {Animals ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; *Genetic Association Studies ; High-Throughput Nucleotide Sequencing ; Larva ; Metamorphosis, Biological/*genetics ; MicroRNAs/*genetics ; RNA Interference ; Reproducibility of Results ; Signal Transduction ; Urochordata/*genetics/growth & development/metabolism ; }, abstract = {BACKGROUND: Metamorphosis takes place within the life cycle of most marine invertebrates. The marine ascidian is a classical model to study complex cellular processes and underlying molecular mechanisms involved in its larval metamorphosis. The detailed molecular signaling pathways remain elusive, though extracellular signal-regulated kinases (ERKs) and c-Jun N-terminal kinase (JNK) have been revealed to regulate cell migration, differentiation, and apoptosis in ascidian larval organ regression and juvenile organ development. MicroRNAs (miRNAs) are small non-coding RNAs that modulate gene expression at the post-transcriptional level. Large numbers of miRNAs have been demonstrated to be involved in many developmental and metamorphic processes. However, the identification of miRNAs in ascidian larval metamorphosis has not yet been investigated.

RESULTS: Totally, 106 known and 59 novel miRNAs were screened out through RNA-sequencing of three small RNA libraries from 18 to 21-h post-fertilization (hpf) tailbud embryos as well as from 42 hpf larvae (after tail regression) in Ciona savignyi. Expression profiling of miRNAs was confirmed by quantitative real-time PCR, showing that the expression levels of csa-miR-4040, csa-miR-4086, csa-miR-4055, csa-miR-4060, csa-miR-216a, csa-miR-216b, csa-miR-217, csa-miR-183, and csa-miR-92c were significantly higher in 42 hpf larvae, whereas those of csa-miR-4018a, csa-miR-4018b, and csa-miR-4000f were higher in 18 and 21 hpf embryos; then, their expression in 42 hpf larvae became significantly low. For these 12 miRNAs, whose expression levels significantly changed, we predicted their target genes through the combination of miRanda and TargetScan. This prediction analysis revealed 332 miRNA-target gene pairs that were associated with the ERK, JNK, and transforming growth factor beta signaling pathways, suggesting that the identified miRNAs are involved in the regulation of C. savignyi larval metamorphosis via controlling the expression of their target genes. Furthermore, we validated the expression of five selected miRNAs by northern blotting. Among the selected miRNAs, the expression patterns of csa-miR-4018a, csa-miR-4018b, and csa-miR-4000f were further examined by whole-mount in situ hybridization. The results showed that all three miRNAs were specifically expressed in a cell population resembling mesenchymal cells at the head and trunk part in swimming larvae but not in metamorphic larvae. Utilizing the luciferase assay, we also confirmed that miR-4000f targeted Mapk1, suggesting that the csa-miR-4018a/csa-miR-4018b/csa-miR-4000f cluster regulates larval metamorphosis through the Mapk1-mediated signaling pathway.

CONCLUSIONS: Totally, 165 miRNAs, including 59 novel ones, were identified from the embryos and larvae of C. savignyi. Twelve of them showed significant changes in expression before and during metamorphosis. In situ hybridization and northern blotting results revealed that three miRNAs are potentially involved in the signaling regulatory network for the migration and differentiation of mesenchymal cells in larval metamorphosis. Furthermore, the luciferase reporter assay revealed that Mapk1 is a target of csa-miR-4000f. Our results not only present a list and profile of miRNAs involved in Ciona metamorphosis but also provide informative cues to further understand their function in ascidian larval metamorphosis.}, } @article {pmid29490612, year = {2018}, author = {Cheng, L and Marinelli, LJ and Grosset, N and Fitz-Gibbon, ST and Bowman, CA and Dang, BQ and Russell, DA and Jacobs-Sera, D and Shi, B and Pellegrini, M and Miller, JF and Gautier, M and Hatfull, GF and Modlin, RL}, title = {Complete genomic sequences of Propionibacterium freudenreichii phages from Swiss cheese reveal greater diversity than Cutibacterium (formerly Propionibacterium) acnes phages.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {19}, pmid = {29490612}, issn = {1471-2180}, support = {P50 CA211015/CA/NCI NIH HHS/United States ; F32-AR060655/AR/NIAMS NIH HHS/United States ; K01-AR066571/AR/NIAMS NIH HHS/United States ; }, abstract = {BACKGROUND: A remarkable exception to the large genetic diversity often observed for bacteriophages infecting a specific bacterial host was found for the Cutibacterium acnes (formerly Propionibacterium acnes) phages, which are highly homogeneous. Phages infecting the related species, which is also a member of the Propionibacteriaceae family, Propionibacterium freudenreichii, a bacterium used in production of Swiss-type cheeses, have also been described and are common contaminants of the cheese manufacturing process. However, little is known about their genetic composition and diversity.

RESULTS: We obtained seven independently isolated bacteriophages that infect P. freudenreichii from Swiss-type cheese samples, and determined their complete genome sequences. These data revealed that all seven phage isolates are of similar genomic length and GC% content, but their genomes are highly diverse, including genes encoding the capsid, tape measure, and tail proteins. In contrast to C. acnes phages, all P. freudenreichii phage genomes encode a putative integrase protein, suggesting they are capable of lysogenic growth. This is supported by the finding of related prophages in some P. freudenreichii strains. The seven phages could further be distinguished as belonging to two distinct genomic types, or 'clusters', based on nucleotide sequences, and host range analyses conducted on a collection of P. freudenreichii strains show a higher degree of host specificity than is observed for the C. acnes phages.

CONCLUSIONS: Overall, our data demonstrate P. freudenreichii bacteriophages are distinct from C. acnes phages, as evidenced by their higher genetic diversity, potential for lysogenic growth, and more restricted host ranges. This suggests substantial differences in the evolution of these related species from the Propionibacteriaceae family and their phages, which is potentially related to their distinct environmental niches.}, } @article {pmid29490610, year = {2018}, author = {Wang, W and Sun, W and Wang, W and Szatkiewicz, J}, title = {A randomized approach to speed up the analysis of large-scale read-count data in the application of CNV detection.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {74}, pmid = {29490610}, issn = {1471-2105}, support = {R01 GM126550/GM/NIGMS NIH HHS/United States ; K01MH093517,R21MH104831/NH/NIH HHS/United States ; IIS1313606,DBI1565137//National Science Foundation (US)/International ; R01GM115833,U01CA105417,U01CA134240,MH090338,HG006703//National Institutes of Health (US)/International ; R01GM105785/NH/NIH HHS/United States ; }, mesh = {Algorithms ; *DNA Copy Number Variations ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Humans ; Linear Models ; Models, Statistical ; }, abstract = {BACKGROUND: The application of high-throughput sequencing in a broad range of quantitative genomic assays (e.g., DNA-seq, ChIP-seq) has created a high demand for the analysis of large-scale read-count data. Typically, the genome is divided into tiling windows and windowed read-count data is generated for the entire genome from which genomic signals are detected (e.g. copy number changes in DNA-seq, enrichment peaks in ChIP-seq). For accurate analysis of read-count data, many state-of-the-art statistical methods use generalized linear models (GLM) coupled with the negative-binomial (NB) distribution by leveraging its ability for simultaneous bias correction and signal detection. However, although statistically powerful, the GLM+NB method has a quadratic computational complexity and therefore suffers from slow running time when applied to large-scale windowed read-count data. In this study, we aimed to speed up substantially the GLM+NB method by using a randomized algorithm and we demonstrate here the utility of our approach in the application of detecting copy number variants (CNVs) using a real example.

RESULTS: We propose an efficient estimator, the randomized GLM+NB coefficients estimator (RGE), for speeding up the GLM+NB method. RGE samples the read-count data and solves the estimation problem on a smaller scale. We first theoretically validated the consistency and the variance properties of RGE. We then applied RGE to GENSENG, a GLM+NB based method for detecting CNVs. We named the resulting method as "R-GENSENG". Based on extensive evaluation using both simulated and empirical data, we concluded that R-GENSENG is ten times faster than the original GENSENG while maintaining GENSENG's accuracy in CNV detection.

CONCLUSIONS: Our results suggest that RGE strategy developed here could be applied to other GLM+NB based read-count analyses, i.e. ChIP-seq data analysis, to substantially improve their computational efficiency while preserving the analytic power.}, } @article {pmid29490607, year = {2018}, author = {Eder, M and Sanchez, I and Brice, C and Camarasa, C and Legras, JL and Dequin, S}, title = {QTL mapping of volatile compound production in Saccharomyces cerevisiae during alcoholic fermentation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {166}, pmid = {29490607}, issn = {1471-2164}, support = {606795//FP7 People: Marie-Curie Actions/International ; }, mesh = {Alcohols/*metabolism ; Amino Acid Substitution ; Chromatography, High Pressure Liquid ; *Chromosome Mapping ; *Fermentation ; Gas Chromatography-Mass Spectrometry ; Genetic Association Studies ; Genome, Fungal ; Genomics/methods ; Lod Score ; Metabolic Networks and Pathways ; Models, Biological ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; Quantitative Trait, Heritable ; Saccharomyces cerevisiae/*genetics/*metabolism ; Secondary Metabolism ; Sugars/metabolism ; Volatile Organic Compounds/*metabolism ; }, abstract = {BACKGROUND: The volatile metabolites produced by Saccharomyces cerevisiae during alcoholic fermentation, which are mainly esters, higher alcohols and organic acids, play a vital role in the quality and perception of fermented beverages, such as wine. Although the metabolic pathways and genes behind yeast fermentative aroma formation are well described, little is known about the genetic mechanisms underlying variations between strains in the production of these aroma compounds. To increase our knowledge about the links between genetic variation and volatile production, we performed quantitative trait locus (QTL) mapping using 130 F2-meiotic segregants from two S. cerevisiae wine strains. The segregants were individually genotyped by next-generation sequencing and separately phenotyped during wine fermentation.

RESULTS: Using different QTL mapping strategies, we were able to identify 65 QTLs in the genome, including 55 that influence the formation of 30 volatile secondary metabolites, 14 with an effect on sugar consumption and central carbon metabolite production, and 7 influencing fermentation parameters. For ethyl lactate, ethyl octanoate and propanol formation, we discovered 2 interacting QTLs each. Within 9 of the detected regions, we validated the contribution of 13 genes in the observed phenotypic variation by reciprocal hemizygosity analysis. These genes are involved in nitrogen uptake and metabolism (AGP1, ALP1, ILV6, LEU9), central carbon metabolism (HXT3, MAE1), fatty acid synthesis (FAS1) and regulation (AGP2, IXR1, NRG1, RGS2, RGT1, SIR2) and explain variations in the production of characteristic sensorial esters (e.g., 2-phenylethyl acetate, 2-metyhlpropyl acetate and ethyl hexanoate), higher alcohols and fatty acids.

CONCLUSIONS: The detection of QTLs and their interactions emphasizes the complexity of yeast fermentative aroma formation. The validation of underlying allelic variants increases knowledge about genetic variation impacting metabolic pathways that lead to the synthesis of sensorial important compounds. As a result, this work lays the foundation for tailoring S. cerevisiae strains with optimized volatile metabolite production for fermented beverages and other biotechnological applications.}, } @article {pmid29490606, year = {2018}, author = {Copley, TR and Duceppe, MO and O'Donoughue, LS}, title = {Identification of novel loci associated with maturity and yield traits in early maturity soybean plant introduction lines.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {167}, pmid = {29490606}, issn = {1471-2164}, mesh = {Alleles ; Chromosome Mapping ; *Genetic Association Studies ; Genetics, Population ; Genome, Plant ; Genome-Wide Association Study ; Genotype ; Linkage Disequilibrium ; Phenotype ; Phylogeny ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; *Quantitative Trait, Heritable ; Soybeans/*physiology ; }, abstract = {BACKGROUND: To continue to meet the increasing demands of soybean worldwide, it is crucial to identify key genes regulating flowering and maturity to expand the cultivated regions into short season areas. Although four soybean genes have been successfully utilized in early maturity breeding programs, new genes governing maturity are continuously being identified suggesting that there remains as yet undiscovered loci governing agronomic traits of interest. The objective of this study was to identify novel loci and genes involved in a diverse set of early soybean maturity using genome-wide association (GWA) analyses to identify loci governing days to maturity (DTM), flowering (DTF) and pod filling (DTPF), as well as yield and 100 seed weight in Canadian environments. To do so, soybean plant introduction lines varying significantly for maturity, but classified as early varieties, were used. Plants were phenotyped for the five agronomic traits for five site-years and GWA approaches used to identify candidate loci and genes affecting each trait.

RESULTS: Genotyping using genotyping-by-sequencing and microarray methods identified 67,594 single nucleotide polymorphisms, of which 31,283 had a linkage disequilibrium < 1 and minor allele frequency > 0.05 and were used for GWA analyses. A total of 9, 6, 4, 5 and 2 loci were detected for GWA analyses for DTM, DTF, DTPF, 100 seed weight and yield, respectively. Regions of interest, including a region surrounding the E1 gene for flowering and maturity, and several novel loci, were identified, with several loci having pleiotropic effects. Novel loci affecting maturity were identified on chromosomes five and 13 and reduced maturity by 7.2 and 3.3 days, respectively. Novel loci for maturity and flowering contained genes orthologous to known Arabidopsis flowering genes, while loci affecting yield and 100 seed weight contained genes known to cause dwarfism.

CONCLUSIONS: This study demonstrated substantial variation in soybean agronomic traits of interest, including maturity and flowering dates as well as yield, and the utility of GWA analyses in identifying novel genetic factors underlying important agronomic traits. The loci and candidate genes identified serve as promising targets for future studies examining the mechanisms underlying the related soybean traits.}, } @article {pmid29489755, year = {2018}, author = {Ma, X and Liu, Y and Liu, Y and Alexandrov, LB and Edmonson, MN and Gawad, C and Zhou, X and Li, Y and Rusch, MC and Easton, J and Huether, R and Gonzalez-Pena, V and Wilkinson, MR and Hermida, LC and Davis, S and Sioson, E and Pounds, S and Cao, X and Ries, RE and Wang, Z and Chen, X and Dong, L and Diskin, SJ and Smith, MA and Guidry Auvil, JM and Meltzer, PS and Lau, CC and Perlman, EJ and Maris, JM and Meshinchi, S and Hunger, SP and Gerhard, DS and Zhang, J}, title = {Pan-cancer genome and transcriptome analyses of 1,699 paediatric leukaemias and solid tumours.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {371-376}, pmid = {29489755}, issn = {1476-4687}, support = {CA21765/CA/NCI NIH HHS/United States ; P30 CA021765/CA/NCI NIH HHS/United States ; U10 CA098543/CA/NCI NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; Aneuploidy ; Child ; DNA Copy Number Variations ; Exome/genetics ; *Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Genome, Human/*genetics ; Humans ; Leukemia/*genetics ; Mutation/*genetics/radiation effects ; Mutation Rate ; Neoplasms/*genetics ; Oncogenes/genetics ; Precision Medicine/trends ; Ultraviolet Rays/adverse effects ; }, abstract = {Analysis of molecular aberrations across multiple cancer types, known as pan-cancer analysis, identifies commonalities and differences in key biological processes that are dysregulated in cancer cells from diverse lineages. Pan-cancer analyses have been performed for adult but not paediatric cancers, which commonly occur in developing mesodermic rather than adult epithelial tissues. Here we present a pan-cancer study of somatic alterations, including single nucleotide variants, small insertions or deletions, structural variations, copy number alterations, gene fusions and internal tandem duplications in 1,699 paediatric leukaemias and solid tumours across six histotypes, with whole-genome, whole-exome and transcriptome sequencing data processed under a uniform analytical framework. We report 142 driver genes in paediatric cancers, of which only 45% match those found in adult pan-cancer studies; copy number alterations and structural variants constituted the majority (62%) of events. Eleven genome-wide mutational signatures were identified, including one attributed to ultraviolet-light exposure in eight aneuploid leukaemias. Transcription of the mutant allele was detectable for 34% of protein-coding mutations, and 20% exhibited allele-specific expression. These data provide a comprehensive genomic architecture for paediatric cancers and emphasize the need for paediatric cancer-specific development of precision therapies.}, } @article {pmid29489754, year = {2018}, author = {Gröbner, SN and Worst, BC and Weischenfeldt, J and Buchhalter, I and Kleinheinz, K and Rudneva, VA and Johann, PD and Balasubramanian, GP and Segura-Wang, M and Brabetz, S and Bender, S and Hutter, B and Sturm, D and Pfaff, E and Hübschmann, D and Zipprich, G and Heinold, M and Eils, J and Lawerenz, C and Erkek, S and Lambo, S and Waszak, S and Blattmann, C and Borkhardt, A and Kuhlen, M and Eggert, A and Fulda, S and Gessler, M and Wegert, J and Kappler, R and Baumhoer, D and Burdach, S and Kirschner-Schwabe, R and Kontny, U and Kulozik, AE and Lohmann, D and Hettmer, S and Eckert, C and Bielack, S and Nathrath, M and Niemeyer, C and Richter, GH and Schulte, J and Siebert, R and Westermann, F and Molenaar, JJ and Vassal, G and Witt, H and , and , and Burkhardt, B and Kratz, CP and Witt, O and van Tilburg, CM and Kramm, CM and Fleischhack, G and Dirksen, U and Rutkowski, S and Frühwald, M and von Hoff, K and Wolf, S and Klingebiel, T and Koscielniak, E and Landgraf, P and Koster, J and Resnick, AC and Zhang, J and Liu, Y and Zhou, X and Waanders, AJ and Zwijnenburg, DA and Raman, P and Brors, B and Weber, UD and Northcott, PA and Pajtler, KW and Kool, M and Piro, RM and Korbel, JO and Schlesner, M and Eils, R and Jones, DTW and Lichter, P and Chavez, L and Zapatka, M and Pfister, SM}, title = {The landscape of genomic alterations across childhood cancers.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {321-327}, pmid = {29489754}, issn = {1476-4687}, mesh = {Adolescent ; Adult ; Child ; Chromothripsis ; Cohort Studies ; DNA Copy Number Variations/genetics ; Diploidy ; Genetic Predisposition to Disease/genetics ; Genome, Human/*genetics ; *Genomics ; Germ-Line Mutation/genetics ; Humans ; Molecular Targeted Therapy ; Mutation/*genetics ; Mutation Rate ; Neoplasms/*classification/drug therapy/*genetics ; Tumor Suppressor Protein p53/genetics ; Young Adult ; }, abstract = {Pan-cancer analyses that examine commonalities and differences among various cancer types have emerged as a powerful way to obtain novel insights into cancer biology. Here we present a comprehensive analysis of genetic alterations in a pan-cancer cohort including 961 tumours from children, adolescents, and young adults, comprising 24 distinct molecular types of cancer. Using a standardized workflow, we identified marked differences in terms of mutation frequency and significantly mutated genes in comparison to previously analysed adult cancers. Genetic alterations in 149 putative cancer driver genes separate the tumours into two classes: small mutation and structural/copy-number variant (correlating with germline variants). Structural variants, hyperdiploidy, and chromothripsis are linked to TP53 mutation status and mutational signatures. Our data suggest that 7-8% of the children in this cohort carry an unambiguous predisposing germline variant and that nearly 50% of paediatric neoplasms harbour a potentially druggable event, which is highly relevant for the design of future clinical trials.}, } @article {pmid29489753, year = {2018}, author = {Rothschild, D and Weissbrod, O and Barkan, E and Kurilshikov, A and Korem, T and Zeevi, D and Costea, PI and Godneva, A and Kalka, IN and Bar, N and Shilo, S and Lador, D and Vila, AV and Zmora, N and Pevsner-Fischer, M and Israeli, D and Kosower, N and Malka, G and Wolf, BC and Avnit-Sagi, T and Lotan-Pompan, M and Weinberger, A and Halpern, Z and Carmi, S and Fu, J and Wijmenga, C and Zhernakova, A and Elinav, E and Segal, E}, title = {Environment dominates over host genetics in shaping human gut microbiota.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {210-215}, pmid = {29489753}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cohort Studies ; Diet/*statistics & numerical data ; *Environment ; *Family Characteristics ; Female ; Gastrointestinal Microbiome/*genetics ; Gene-Environment Interaction ; Glucose/metabolism ; Healthy Volunteers ; Heredity/genetics ; Humans ; Israel ; *Life Style ; Male ; Middle Aged ; Obesity/metabolism ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; RNA, Bacterial/analysis/genetics ; RNA, Ribosomal, 16S/analysis ; Reproducibility of Results ; Twin Studies as Topic ; Twins/genetics ; Young Adult ; }, abstract = {Human gut microbiome composition is shaped by multiple factors but the relative contribution of host genetics remains elusive. Here we examine genotype and microbiome data from 1,046 healthy individuals with several distinct ancestral origins who share a relatively common environment, and demonstrate that the gut microbiome is not significantly associated with genetic ancestry, and that host genetics have a minor role in determining microbiome composition. We show that, by contrast, there are significant similarities in the compositions of the microbiomes of genetically unrelated individuals who share a household, and that over 20% of the inter-person microbiome variability is associated with factors related to diet, drugs and anthropometric measurements. We further demonstrate that microbiome data significantly improve the prediction accuracy for many human traits, such as glucose and obesity measures, compared to models that use only host genetic and environmental data. These results suggest that microbiome alterations aimed at improving clinical outcomes may be carried out across diverse genetic backgrounds.}, } @article {pmid29489752, year = {2018}, author = {Zacharias, WJ and Frank, DB and Zepp, JA and Morley, MP and Alkhaleel, FA and Kong, J and Zhou, S and Cantu, E and Morrisey, EE}, title = {Regeneration of the lung alveolus by an evolutionarily conserved epithelial progenitor.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {251-255}, pmid = {29489752}, issn = {1476-4687}, support = {R01 HL087825/HL/NHLBI NIH HHS/United States ; T32 HL007586/HL/NHLBI NIH HHS/United States ; R01 HL132349/HL/NHLBI NIH HHS/United States ; T32 HL007915/HL/NHLBI NIH HHS/United States ; U01 HL134745/HL/NHLBI NIH HHS/United States ; K23 HL116656/HL/NHLBI NIH HHS/United States ; U01 HL110942/HL/NHLBI NIH HHS/United States ; P30 ES013508/ES/NIEHS NIH HHS/United States ; K12 HD043245/HD/NICHD NIH HHS/United States ; T32 HL007843/HL/NHLBI NIH HHS/United States ; K08 HL140129/HL/NHLBI NIH HHS/United States ; HL129478/NH/NIH HHS/United States ; R01 HL132999/HL/NHLBI NIH HHS/United States ; }, mesh = {Acute Lung Injury/pathology/surgery ; Animals ; Antigens, Surface/metabolism ; Axin Protein/metabolism ; Biomarkers/metabolism ; Cell Cycle ; Cell Lineage ; Chromatin/genetics/metabolism ; Epigenomics ; Epithelial Cells/*cytology/metabolism ; *Evolution, Molecular ; Female ; Fibroblast Growth Factors/metabolism ; Humans ; Male ; Mice ; Neoplasm Proteins/metabolism ; Organoids/cytology/metabolism ; Pulmonary Alveoli/*cytology ; *Regeneration ; Stem Cells/*cytology/metabolism ; Transcriptome ; Wnt Signaling Pathway ; }, abstract = {Functional tissue regeneration is required for the restoration of normal organ homeostasis after severe injury. Some organs, such as the intestine, harbour active stem cells throughout homeostasis and regeneration; more quiescent organs, such as the lung, often contain facultative progenitor cells that are recruited after injury to participate in regeneration. Here we show that a Wnt-responsive alveolar epithelial progenitor (AEP) lineage within the alveolar type 2 cell population acts as a major facultative progenitor cell in the distal lung. AEPs are a stable lineage during alveolar homeostasis but expand rapidly to regenerate a large proportion of the alveolar epithelium after acute lung injury. AEPs exhibit a distinct transcriptome, epigenome and functional phenotype and respond specifically to Wnt and Fgf signalling. In contrast to other proposed lung progenitor cells, human AEPs can be directly isolated by expression of the conserved cell surface marker TM4SF1, and act as functional human alveolar epithelial progenitor cells in 3D organoids. Our results identify the AEP lineage as an evolutionarily conserved alveolar progenitor that represents a new target for human lung regeneration strategies.}, } @article {pmid29489751, year = {2018}, author = {Stappers, MHT and Clark, AE and Aimanianda, V and Bidula, S and Reid, DM and Asamaphan, P and Hardison, SE and Dambuza, IM and Valsecchi, I and Kerscher, B and Plato, A and Wallace, CA and Yuecel, R and Hebecker, B and da Glória Teixeira Sousa, M and Cunha, C and Liu, Y and Feizi, T and Brakhage, AA and Kwon-Chung, KJ and Gow, NAR and Zanda, M and Piras, M and Zanato, C and Jaeger, M and Netea, MG and van de Veerdonk, FL and Lacerda, JF and Campos, A and Carvalho, A and Willment, JA and Latgé, JP and Brown, GD}, title = {Recognition of DHN-melanin by a C-type lectin receptor is required for immunity to Aspergillus.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {382-386}, pmid = {29489751}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Aspergillosis/immunology/microbiology/prevention & control ; Aspergillus fumigatus/chemistry/*immunology/pathogenicity ; Cell Wall/chemistry/immunology ; Female ; Humans ; Lectins, C-Type/*immunology ; Macrophages/immunology ; Melanins/chemistry/*immunology ; Mice ; Mice, Inbred C57BL ; Naphthols/chemistry/*immunology ; Rats ; Rats, Sprague-Dawley ; Spores, Fungal/chemistry/immunology ; Substrate Specificity ; }, abstract = {Resistance to infection is critically dependent on the ability of pattern recognition receptors to recognize microbial invasion and induce protective immune responses. One such family of receptors are the C-type lectins, which are central to antifungal immunity. These receptors activate key effector mechanisms upon recognition of conserved fungal cell-wall carbohydrates. However, several other immunologically active fungal ligands have been described; these include melanin, for which the mechanism of recognition is hitherto undefined. Here we identify a C-type lectin receptor, melanin-sensing C-type lectin receptor (MelLec), that has an essential role in antifungal immunity through recognition of the naphthalene-diol unit of 1,8-dihydroxynaphthalene (DHN)-melanin. MelLec recognizes melanin in conidial spores of Aspergillus fumigatus as well as in other DHN-melanized fungi. MelLec is ubiquitously expressed by CD31+ endothelial cells in mice, and is also expressed by a sub-population of these cells that co-express epithelial cell adhesion molecule and are detected only in the lung and the liver. In mouse models, MelLec was required for protection against disseminated infection with A. fumigatus. In humans, MelLec is also expressed by myeloid cells, and we identified a single nucleotide polymorphism of this receptor that negatively affected myeloid inflammatory responses and significantly increased the susceptibility of stem-cell transplant recipients to disseminated Aspergillus infections. MelLec therefore recognizes an immunologically active component commonly found on fungi and has an essential role in protective antifungal immunity in both mice and humans.}, } @article {pmid29489750, year = {2018}, author = {Bertero, A and Brown, S and Madrigal, P and Osnato, A and Ortmann, D and Yiangou, L and Kadiwala, J and Hubner, NC and de Los Mozos, IR and Sadée, C and Lenaerts, AS and Nakanoh, S and Grandy, R and Farnell, E and Ule, J and Stunnenberg, HG and Mendjan, S and Vallier, L}, title = {The SMAD2/3 interactome reveals that TGFβ controls m6A mRNA methylation in pluripotency.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {256-259}, pmid = {29489750}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; 281335//European Research Council/International ; MC_U105185858//Medical Research Council/United Kingdom ; }, mesh = {Activins/metabolism ; Adenosine/*analogs & derivatives/metabolism ; Animals ; Cell Differentiation/*genetics ; Epigenesis, Genetic ; Humans ; Methylation ; Methyltransferases/chemistry/metabolism ; Multiprotein Complexes/chemistry/metabolism ; Nanog Homeobox Protein/metabolism ; Nodal Protein/metabolism ; Nuclear Proteins/metabolism ; Pluripotent Stem Cells/cytology/*metabolism ; Protein Binding ; RNA, Messenger/chemistry/genetics/*metabolism ; Signal Transduction ; Smad2 Protein/*metabolism ; Smad3 Protein/*metabolism ; Transcriptome ; Transforming Growth Factor beta/*metabolism ; }, abstract = {The TGFβ pathway has essential roles in embryonic development, organ homeostasis, tissue repair and disease. These diverse effects are mediated through the intracellular effectors SMAD2 and SMAD3 (hereafter SMAD2/3), whose canonical function is to control the activity of target genes by interacting with transcriptional regulators. Therefore, a complete description of the factors that interact with SMAD2/3 in a given cell type would have broad implications for many areas of cell biology. Here we describe the interactome of SMAD2/3 in human pluripotent stem cells. This analysis reveals that SMAD2/3 is involved in multiple molecular processes in addition to its role in transcription. In particular, we identify a functional interaction with the METTL3-METTL14-WTAP complex, which mediates the conversion of adenosine to N6-methyladenosine (m6A) on RNA. We show that SMAD2/3 promotes binding of the m6A methyltransferase complex to a subset of transcripts involved in early cell fate decisions. This mechanism destabilizes specific SMAD2/3 transcriptional targets, including the pluripotency factor gene NANOG, priming them for rapid downregulation upon differentiation to enable timely exit from pluripotency. Collectively, these findings reveal the mechanism by which extracellular signalling can induce rapid cellular responses through regulation of the epitranscriptome. These aspects of TGFβ signalling could have far-reaching implications in many other cell types and in diseases such as cancer.}, } @article {pmid29489749, year = {2018}, author = {Douglas, ME and Ali, FA and Costa, A and Diffley, JFX}, title = {The mechanism of eukaryotic CMG helicase activation.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {265-268}, pmid = {29489749}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Adenosine Diphosphate/chemistry/metabolism ; Adenosine Triphosphate/chemistry/metabolism ; Cell Cycle Proteins/metabolism ; DNA Helicases/chemistry/*metabolism ; *DNA Replication ; DNA, Single-Stranded/biosynthesis/chemistry/metabolism ; DNA-Binding Proteins/metabolism ; Enzyme Activation ; Enzyme Stability ; Minichromosome Maintenance Proteins/metabolism ; Nucleic Acid Conformation ; Replication Origin ; Saccharomyces cerevisiae/*enzymology ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; }, abstract = {The initiation of eukaryotic DNA replication occurs in two discrete stages: first, the minichromosome maintenance (MCM) complex assembles as a head-to-head double hexamer that encircles duplex replication origin DNA during G1 phase; then, 'firing factors' convert each double hexamer into two active Cdc45-MCM-GINS helicases (CMG) during S phase. This second stage requires separation of the two origin DNA strands and remodelling of the double hexamer so that each MCM hexamer encircles a single DNA strand. Here we show that the MCM complex, which hydrolyses ATP during double-hexamer formation, remains stably bound to ADP in the double hexamer. Firing factors trigger ADP release, and subsequent ATP binding promotes stable CMG assembly. CMG assembly is accompanied by initial DNA untwisting and separation of the double hexamer into two discrete but inactive CMG helicases. Mcm10, together with ATP hydrolysis, then triggers further DNA untwisting and helicase activation. After activation, the two CMG helicases translocate in an 'N terminus-first' direction, and in doing so pass each other within the origin; this requires that each helicase is bound entirely to single-stranded DNA. Our experiments elucidate the mechanism of eukaryotic replicative helicase activation, which we propose provides a fail-safe mechanism for bidirectional replisome establishment.}, } @article {pmid29489748, year = {2018}, author = {Nishida, KM and Sakakibara, K and Iwasaki, YW and Yamada, H and Murakami, R and Murota, Y and Kawamura, T and Kodama, T and Siomi, H and Siomi, MC}, title = {Hierarchical roles of mitochondrial Papi and Zucchini in Bombyx germline piRNA biogenesis.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {260-264}, pmid = {29489748}, issn = {1476-4687}, mesh = {Animals ; Argonaute Proteins/metabolism ; Bombyx/*cytology/*genetics ; Drosophila ; Endoribonucleases/*metabolism ; Germ Cells/*metabolism ; Mitochondrial Proteins/*metabolism ; RNA, Small Interfering/*biosynthesis/genetics ; }, abstract = {PIWI-interacting RNAs (piRNAs) are small regulatory RNAs that bind to PIWI proteins to control transposons and maintain genome integrity in animal germ lines. piRNA 3' end formation in the silkworm Bombyx mori has been shown to be mediated by the 3'-to-5' exonuclease Trimmer (Trim; known as PNLDC1 in mammals), and piRNA intermediates are bound with PIWI anchored onto mitochondrial Tudor domain protein Papi. However, it remains unclear whether the Zucchini (Zuc) endonuclease and Nibbler (Nbr) 3'-to-5' exonuclease, both of which have pivotal roles in piRNA biogenesis in Drosophila, are required for piRNA processing in other species. Here we show that the loss of Zuc in Bombyx had no effect on the levels of Trim and Nbr, but resulted in the aberrant accumulation of piRNA intermediates within the Papi complex, and that these were processed to form mature piRNAs by recombinant Zuc. Papi exerted its RNA-binding activity only when bound with PIWI and phosphorylated, suggesting that complex assembly involves a hierarchical process. Both the 5' and 3' ends of piRNA intermediates within the Papi complex showed hallmarks of PIWI 'slicer' activity, yet no phasing pattern was observed in mature piRNAs. The loss of Zuc did not affect the 5'- and 3'-end formation of the intermediates, strongly supporting the idea that the 5' end of Bombyx piRNA is formed by PIWI slicer activity, but independently of Zuc, whereas the 3' end is formed by the Zuc endonuclease. The Bombyx piRNA biogenesis machinery is simpler than that of Drosophila, because Bombyx has no transcriptional silencing machinery that relies on phased piRNAs.}, } @article {pmid29489747, year = {2018}, author = {Augustine, V and Gokce, SK and Lee, S and Wang, B and Davidson, TJ and Reimann, F and Gribble, F and Deisseroth, K and Lois, C and Oka, Y}, title = {Hierarchical neural architecture underlying thirst regulation.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {204-209}, pmid = {29489747}, issn = {1476-4687}, support = {MC_UU_12012/3//Medical Research Council/United Kingdom ; MC_UU_12012/5//Medical Research Council/United Kingdom ; R56 MH113030/MH/NIMH NIH HHS/United States ; U01 NS099717/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Appetite/physiology ; Drinking/*physiology ; Female ; GABAergic Neurons/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; Homeostasis ; Instinct ; Male ; Mice ; *Neural Pathways ; Nitric Oxide Synthase/metabolism ; Preoptic Area/*cytology/*physiology ; Satiety Response/physiology ; Subfornical Organ/*cytology/*physiology ; Thirst/*physiology ; Water-Electrolyte Balance ; }, abstract = {Neural circuits for appetites are regulated by both homeostatic perturbations and ingestive behaviour. However, the circuit organization that integrates these internal and external stimuli is unclear. Here we show in mice that excitatory neural populations in the lamina terminalis form a hierarchical circuit architecture to regulate thirst. Among them, nitric oxide synthase-expressing neurons in the median preoptic nucleus (MnPO) are essential for the integration of signals from the thirst-driving neurons of the subfornical organ (SFO). Conversely, a distinct inhibitory circuit, involving MnPO GABAergic neurons that express glucagon-like peptide 1 receptor (GLP1R), is activated immediately upon drinking and monosynaptically inhibits SFO thirst neurons. These responses are induced by the ingestion of fluids but not solids, and are time-locked to the onset and offset of drinking. Furthermore, loss-of-function manipulations of GLP1R-expressing MnPO neurons lead to a polydipsic, overdrinking phenotype. These neurons therefore facilitate rapid satiety of thirst by monitoring real-time fluid ingestion. Our study reveals dynamic thirst circuits that integrate the homeostatic-instinctive requirement for fluids and the consequent drinking behaviour to maintain internal water balance.}, } @article {pmid29489400, year = {2018}, author = {Cadotte, MW and Campbell, SE and Li, SP and Sodhi, DS and Mandrak, NE}, title = {Preadaptation and Naturalization of Nonnative Species: Darwin's Two Fundamental Insights into Species Invasion.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {661-684}, doi = {10.1146/annurev-arplant-042817-040339}, pmid = {29489400}, issn = {1545-2123}, abstract = {Predicting which nonnative species become invasive is critical for their successful management, and Charles Darwin provided predictions based on species' relatedness. However, Darwin provided two opposing predictions about the relatedness of introduced nonnatives to indigenous species. First, environmental fit is the dominant factor determining invader success; thus, we should expect that invasive species are closely related to local native residents. Alternatively, if competition is important, we should expect successful invaders are distantly related to the native residents. These opposing expectations are referred to as Darwin's naturalization conundrum. The results of studies that examine nonnative species relatedness to natives are largely inconsistent. This inconsistency arises from the fact that studies occur at different spatial and temporal scales, and at different stages of invasion, and so implicitly examine different mechanisms. Further, while species have evolved ecological differences, the mode and tempo of evolution can affect species' differences, complicating the predictions from simple hypotheses. We outline unanswered questions and provide guidelines for collecting the data required to test competing hypotheses.}, } @article {pmid29489399, year = {2018}, author = {Vamosi, JC and Magallón, S and Mayrose, I and Otto, SP and Sauquet, H}, title = {Macroevolutionary Patterns of Flowering Plant Speciation and Extinction.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {685-706}, doi = {10.1146/annurev-arplant-042817-040348}, pmid = {29489399}, issn = {1545-2123}, abstract = {Species diversity is remarkably unevenly distributed among flowering plant lineages. Despite a growing toolbox of research methods, the reasons underlying this patchy pattern have continued to perplex plant biologists for the past two decades. In this review, we examine the present understanding of transitions in flowering plant evolution that have been proposed to influence speciation and extinction. In particular, ploidy changes, transitions between tropical and nontropical biomes, and shifts in floral form have received attention and have offered some surprises in terms of which factors influence speciation and extinction rates. Mating systems and dispersal characteristics once predominated as determining factors, yet recent evidence suggests that these changes are not as influential as previously thought or are important only when paired with range shifts. Although range extent is an important correlate of speciation, it also influences extinction and brings an applied focus to diversification research. Recent studies that find that past diversification can predict present-day extinction risk open an exciting avenue for future research to help guide conservation prioritization.}, } @article {pmid29489398, year = {2018}, author = {Komis, G and Šamajová, O and Ovečka, M and Šamaj, J}, title = {Cell and Developmental Biology of Plant Mitogen-Activated Protein Kinases.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {237-265}, doi = {10.1146/annurev-arplant-042817-040314}, pmid = {29489398}, issn = {1545-2123}, abstract = {Plant mitogen-activated protein kinases (MAPKs) constitute a network of signaling cascades responsible for transducing extracellular stimuli and decoding them to dedicated cellular and developmental responses that shape the plant body. Over the last decade, we have accumulated information about how MAPK modules control the development of reproductive tissues and gametes and the embryogenic and postembryonic development of vegetative organs such as roots, root nodules, shoots, and leaves. Of key importance to understanding how MAPKs participate in developmental and environmental signaling is the characterization of their subcellular localization, their interactions with upstream signal perception mechanisms, and the means by which they target their substrates. In this review, we summarize the roles of MAPK signaling in the regulation of key plant developmental processes, and we survey what is known about the mechanisms guiding the subcellular compartmentalization of MAPK modules.}, } @article {pmid29489397, year = {2018}, author = {Zhao, Y}, title = {Essential Roles of Local Auxin Biosynthesis in Plant Development and in Adaptation to Environmental Changes.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {417-435}, doi = {10.1146/annurev-arplant-042817-040226}, pmid = {29489397}, issn = {1545-2123}, abstract = {It has been a dominant dogma in plant biology that the self-organizing polar auxin transport system is necessary and sufficient to generate auxin maxima and minima that are essential for almost all aspects of plant growth and development. However, in the past few years, it has become clear that local auxin biosynthesis is required for a suite of developmental processes, including embryogenesis, endosperm development, root development, and floral initiation and patterning. Moreover, it was discovered that local auxin biosynthesis maintains optimal plant growth in response to environmental signals, including light, temperature, pathogens, and toxic metals. In this article, I discuss the recent progress in auxin biosynthesis research and the paradigm shift in recognizing the important roles of local auxin biosynthesis in plant biology.}, } @article {pmid29489396, year = {2018}, author = {Nowack, ECM and Weber, APM}, title = {Genomics-Informed Insights into Endosymbiotic Organelle Evolution in Photosynthetic Eukaryotes.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {51-84}, doi = {10.1146/annurev-arplant-042817-040209}, pmid = {29489396}, issn = {1545-2123}, abstract = {The conversion of free-living cyanobacteria to photosynthetic organelles of eukaryotic cells through endosymbiosis transformed the biosphere and eventually provided the basis for life on land. Despite the presumable advantage conferred by the acquisition of photoautotrophy through endosymbiosis, only two independent cases of primary endosymbiosis have been documented: one that gave rise to the Archaeplastida, and the other to photosynthetic species of the thecate, filose amoeba Paulinella. Here, we review recent genomics-informed insights into the primary endosymbiotic origins of cyanobacteria-derived organelles. Furthermore, we discuss the preconditions for the evolution of nitrogen-fixing organelles. Recent genomic data on previously undersampled cyanobacterial and protist taxa provide new clues to the origins of the host cell and endosymbiont, and proteomic approaches allow insights into the rearrangement of the endosymbiont proteome during organellogenesis. We conclude that in addition to endosymbiotic gene transfers, horizontal gene acquisitions from a broad variety of prokaryotic taxa were crucial to organelle evolution.}, } @article {pmid29489395, year = {2018}, author = {Ramankutty, N and Mehrabi, Z and Waha, K and Jarvis, L and Kremen, C and Herrero, M and Rieseberg, LH}, title = {Trends in Global Agricultural Land Use: Implications for Environmental Health and Food Security.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {789-815}, doi = {10.1146/annurev-arplant-042817-040256}, pmid = {29489395}, issn = {1545-2123}, abstract = {The eighteenth-century Malthusian prediction of population growth outstripping food production has not yet come to bear. Unprecedented agricultural land expansions since 1700, and technological innovations that began in the 1930s, have enabled more calorie production per capita than was ever available before in history. This remarkable success, however, has come at a great cost. Agriculture is a major cause of global environmental degradation. Malnutrition persists among large sections of the population, and a new epidemic of obesity is on the rise. We review both the successes and failures of the global food system, addressing ongoing debates on pathways to environmental health and food security. To deal with these challenges, a new coordinated research program blending modern breeding with agro-ecological methods is needed. We call on plant biologists to lead this effort and help steer humanity toward a safe operating space for agriculture.}, } @article {pmid29489394, year = {2018}, author = {Waszczak, C and Carmody, M and Kangasjärvi, J}, title = {Reactive Oxygen Species in Plant Signaling.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {209-236}, doi = {10.1146/annurev-arplant-042817-040322}, pmid = {29489394}, issn = {1545-2123}, abstract = {As fixed organisms, plants are especially affected by changes in their environment and have consequently evolved extensive mechanisms for acclimation and adaptation. Initially considered by-products from aerobic metabolism, reactive oxygen species (ROS) have emerged as major regulatory molecules in plants and their roles in early signaling events initiated by cellular metabolic perturbation and environmental stimuli are now established. Here, we review recent advances in ROS signaling. Compartment-specific and cross-compartmental signaling pathways initiated by the presence of ROS are discussed. Special attention is dedicated to established and hypothetical ROS-sensing events. The roles of ROS in long-distance signaling, immune responses, and plant development are evaluated. Finally, we outline the most challenging contemporary questions in the field of plant ROS biology and the need to further elucidate mechanisms allowing sensing, signaling specificity, and coordination of multiple signals.}, } @article {pmid29489393, year = {2018}, author = {Wang, L and Xue, Y and Xing, J and Song, K and Lin, J}, title = {Exploring the Spatiotemporal Organization of Membrane Proteins in Living Plant Cells.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {525-551}, doi = {10.1146/annurev-arplant-042817-040233}, pmid = {29489393}, issn = {1545-2123}, abstract = {Plasma membrane proteins have important roles in transport and signal transduction. Deciphering the spatiotemporal organization of these proteins provides crucial information for elucidating the links between the behaviors of different molecules. However, monitoring membrane proteins without disrupting their membrane environment remains difficult. Over the past decade, many studies have developed single-molecule techniques, opening avenues for probing the stoichiometry and interactions of membrane proteins in their native environment by providing nanometer-scale spatial information and nanosecond-scale temporal information. In this review, we assess recent progress in the development of labeling and imaging technology for membrane protein analysis. We focus in particular on several single-molecule techniques for quantifying the dynamics and assembly of membrane proteins. Finally, we provide examples of how these new techniques are advancing our understanding of the complex biological functions of membrane proteins.}, } @article {pmid29489392, year = {2018}, author = {Wang, Y and Copenhaver, GP}, title = {Meiotic Recombination: Mixing It Up in Plants.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {577-609}, doi = {10.1146/annurev-arplant-042817-040431}, pmid = {29489392}, issn = {1545-2123}, abstract = {Meiosis halves diploid chromosome numbers to haploid levels that are essential for sexual reproduction in most eukaryotes. Meiotic recombination ensures the formation of bivalents between homologous chromosomes (homologs) and their subsequent proper segregation. It also results in genetic diversity among progeny that influences evolutionary responses to selection. Moreover, crop breeding depends upon the action of meiotic recombination to rearrange elite traits between parental chromosomes. An understanding of the molecular mechanisms that drive meiotic recombination is important for both fundamental research and practical applications. This review emphasizes advances made during the past 5 years, primarily in Arabidopsis and rice, by summarizing newly characterized genes and proteins and examining the regulatory mechanisms that modulate their action.}, } @article {pmid29489391, year = {2018}, author = {Nebenführ, A and Dixit, R}, title = {Kinesins and Myosins: Molecular Motors that Coordinate Cellular Functions in Plants.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {329-361}, doi = {10.1146/annurev-arplant-042817-040024}, pmid = {29489391}, issn = {1545-2123}, abstract = {Kinesins and myosins are motor proteins that can move actively along microtubules and actin filaments, respectively. Plants have evolved a unique set of motors that function as regulators and organizers of the cytoskeleton and as drivers of long-distance transport of various cellular components. Recent progress has established the full complement of motors encoded in plant genomes and has revealed valuable insights into the cellular functions of many kinesin and myosin isoforms. Interestingly, several of the motors were found to functionally connect the two cytoskeletal systems and thereby to coordinate their activities. In this review, we discuss the available genetic, cell biological, and biochemical data for each of the plant kinesin and myosin families from the context of their subcellular mechanism of action as well as their physiological function in the whole plant. We particularly emphasize work that illustrates mechanisms by which kinesins and myosins coordinate the activities of the cytoskeletal system.}, } @article {pmid29488868, year = {2018}, author = {Pérez-Cataluña, A and Salas-Massó, N and Figueras, MJ}, title = {Arcobacter canalis sp. nov., isolated from a water canal contaminated with urban sewage.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1258-1264}, doi = {10.1099/ijsem.0.002662}, pmid = {29488868}, issn = {1466-5034}, mesh = {Arcobacter/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Shellfish/*microbiology ; Spain ; *Water Microbiology ; }, abstract = {Four bacterial strains recovered from shellfish (n=3) and from the water (n=1) of a canal contaminated with urban sewage were recognized as belonging to a novel species of the genus Arcobacter (represented by strain F138-33T) by using a polyphasic characterization. All the new isolates required 2 % NaCl to grow. Phylogenetic analyses based on 16S rRNA gene sequences indicated that all strains clustered together, with the most closely related species being Arcobacter marinus and Arcobactermolluscorum. However, phylogenetic analyses using the concatenated sequences of housekeeping genes (atpA, gyrB, hsp60, gyrA and rpoB) showed that all the novel strains formed a distinct lineage within the genus Arcobacter. Results of in silico DNA-DNA hybridization and the average nucleotide identity between the genome of strain F138-33T and those of the closely related species A. marinus and other relatively closely related species such as A. molluscorum and Arcobacterhalophilus were all below 70 and 96 %, respectively. All the above results, together with the 15 physiological and biochemical tests that could distinguish the newly isolated strains from the closely related species, confirmed that these strains represent a novel species for which the name Arcobacter canalis sp. nov. is proposed, with the type strain F138-33T (=CECT 8984T=LMG 29148T).}, } @article {pmid29488866, year = {2018}, author = {Park, S and Choi, J and Won, SM and Yoon, JH}, title = {Thalassotalea insulae sp. nov., isolated from tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1321-1326}, doi = {10.1099/ijsem.0.002671}, pmid = {29488866}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Islands ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, motile and rod-shaped or ovoid bacterial strain, designated JDTF-40T, was isolated from a tidal flat in Jindo, an island of the Republic of South Korea. Strain JDTF-40T grew optimally at pH 7.0-8.0, at 30 °C and in the presence of 2 % (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain JDTF-40T fell within the cluster comprising the type strains of Thalassotalea species. Strain JDTF-40T exhibited 16S rRNA gene sequence similarity values of 93.8-95.7 % to the type strains of Thalassotalea species. Strain JDTF-40T contained Q-8 as the predominant ubiquinone and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0 as the major fatty acids. The major polar lipids of strain JDTF-40T were phosphatidylglycerol, phosphatidylethanolamine, one unidentified aminolipid, one unidentified glycolipid and three unidentified lipids. The DNA G+C content of strain JDTF-40T was 41.3 mol%. Differential phenotypic properties, together with the phylogenetic distinctiveness, demonstrated that strain JDTF-40T is distinct from recognized species of the genus Thalassotalea. On the basis of the data presented here, strain JDTF-40T is considered to represent a novel species of the genus Thalassotalea, for which the name Thalassotalea insulae sp. nov. is proposed. The type strain is JDTF-40T (=KACC 19433T=KCTC 62186T=NBRC 113040T).}, } @article {pmid29488862, year = {2018}, author = {Liu, Y and Zhang, X and Lai, Q and Shao, Z}, title = {Reclassification of Mameliella phaeodactyli, Mameliella atlantica, Ponticoccus lacteus and Alkalimicrobium pacificum as later heterotypic synonyms of Mameliella alba and an emended description of Mameliella alba.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1047-1051}, doi = {10.1099/ijsem.0.002617}, pmid = {29488862}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification ; Sequence Analysis, DNA ; }, abstract = {The aim of the study was to reclarify the taxonomic status of four species, Mameliella phaeodactyli, Mameliella atlantica, Ponticoccus lacteus and Alkalimicrobium pacificum, by using a polyphasic taxonomic approach. A combination of physiological properties of the four type strains, KD53T, L6M1-5T, JL351T and F15T, was consistent with those of the closest type strain JLT354-WT of Mameliella alba. The 16S rRNA gene sequences of the five type strains shared 100 % identity. The close relationship between the five strains was underpinned by the results of chemotaxonomic characteristics, including the fatty acids, quinone and polar lipids. The pairwise digital DNA-DNA hybridization values among the five strains were well above 70 %, considered the threshold value for species definition. In this case a further statement of Rule 24a applies, in which priority of names is determined by the date of the original publication. Hence, we propose that that Mameliella phaeodactyli, Mameliella atlantica, Ponticoccus lacteus and Alkalimicrobium pacificum should be regarded as later heterotypic synonyms of Mameliella alba.}, } @article {pmid29488354, year = {2018}, author = {Bayer-Santos, E and Lima, LDP and Ceseti, LM and Ratagami, CY and de Santana, ES and da Silva, AM and Farah, CS and Alvarez-Martinez, CE}, title = {Xanthomonas citri T6SS mediates resistance to Dictyostelium predation and is regulated by an ECF σ factor and cognate Ser/Thr kinase.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1562-1575}, doi = {10.1111/1462-2920.14085}, pmid = {29488354}, issn = {1462-2920}, abstract = {Plant-associated bacteria of the genus Xanthomonas cause disease in a wide range of economically important crops. However, their ability to persist in the environment is still poorly understood. Predation by amoebas represents a major selective pressure to bacterial populations in the environment. In this study, we show that the X. citri type 6 secretion system (T6SS) promotes resistance to predation by the soil amoeba Dictyostelium discoideum. We found that an extracytoplasmic function (ECF) sigma factor (EcfK) is required for induction of T6SS genes during interaction with Dictyostelium. EcfK homologues are found in several environmental bacteria in association with a gene encoding a eukaryotic-like Ser/Thr kinase (pknS). Deletion of pknS causes sensitivity to amoeba predation and abolishes induction of T6SS genes. Phosphomimetic mutagenesis of EcfK identified a threonine residue (T51) that renders EcfK constitutively active in standard culture conditions. Moreover, susceptibility of ΔpknS to Dictyostelium predation can be overcome by expression of the constitutively active version EcfKT51E from a multicopy plasmid. Together, these results describe a new regulatory cascade in which PknS functions through activation of EcfK to promote T6SS expression. Our work reveals an important aspect of Xanthomonas physiology that affects its ability to persist in the environment.}, } @article {pmid29488352, year = {2018}, author = {Wilson, JM and Litvin, SY and Beman, JM}, title = {Microbial community networks associated with variations in community respiration rates during upwelling in nearshore Monterey Bay, California.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {272-282}, doi = {10.1111/1758-2229.12635}, pmid = {29488352}, issn = {1758-2229}, abstract = {Respiration of organic material is a central process in the global carbon (C) cycle catalysed by diverse microbial communities. In the coastal ocean, upwelling can drive variation in both community respiration (CR) and the microbial community, but linkages between the two are not well-understood. We measured CR rates and analysed microbial dynamics via 16S rRNA gene sequencing, to assess whether CR correlated with upwelling irrespective of changes in the microbial community, or if the particular microbial community present was a factor in explaining variations in CR. CR varied significantly over time as a function of temperature, dissolved oxygen (DO) and chlorophyll-all of which are altered by upwelling-but also varied with a 'subnetwork' (i.e., a group of microbial taxa that covaried with one another) of the whole community. One subnetwork was associated with higher CR and warmer temperatures, while another was associated with lower CR and DO. Our results suggest that CR in the coastal ocean varies with both environmental variables, and a portion of the microbial community that is not directly correlated with upwelling intensity.}, } @article {pmid29488349, year = {2018}, author = {Lang-Yona, N and Maier, S and Macholdt, DS and Müller-Germann, I and Yordanova, P and Rodriguez-Caballero, E and Jochum, KP and Al-Amri, A and Andreae, MO and Fröhlich-Nowoisky, J and Weber, B}, title = {Insights into microbial involvement in desert varnish formation retrieved from metagenomic analysis.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {264-271}, doi = {10.1111/1758-2229.12634}, pmid = {29488349}, issn = {1758-2229}, abstract = {Desert varnishes are dark rock coatings observed in arid environments and might resemble Mn-rich coatings found on Martian rocks. Their formation mechanism is not fully understood and the possible microbial involvement is under debate. In this study, we applied DNA metagenomic Shotgun sequencing of varnish and surrounding soil to evaluate the composition of the microbial community and its potential metabolic function. We found that the α diversity was lower in varnish compared to soil samples (p value < 0.05), suggesting distinct populations with significantly higher abundance of Actinobacteria, Proteobacteria and Cyanobacteria within the varnish. Additionally, we observed increased levels of transition metal metabolic processes in varnish compared to soil samples. Nevertheless, potentially relevant enzymes for varnish formation were detected at low to insignificant levels in both niches, indicating no current direct microbial involvement in Mn oxidation. This finding is supported by quantitative genomic analysis, elemental analysis, fluorescence imaging and scanning transmission X-ray microscopy. We thus conclude that the distinct microbial communities detected in desert varnish originate from settled Aeolian microbes, which colonized this nutrient-enriched niche, and discuss possible indirect contributions of microorganisms to the formation of desert varnish.}, } @article {pmid29488315, year = {2018}, author = {Suzuki, DG and Grillner, S}, title = {The stepwise development of the lamprey visual system and its evolutionary implications.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1461-1477}, doi = {10.1111/brv.12403}, pmid = {29488315}, issn = {1469-185X}, abstract = {Lampreys, which represent the oldest group of living vertebrates (cyclostomes), show unique eye development. The lamprey larva has only eyespot-like immature eyes beneath a non-transparent skin, whereas after metamorphosis, the adult has well-developed image-forming camera eyes. To establish a functional visual system, well-organised visual centres as well as motor components (e.g. trunk muscles for locomotion) and interactions between them are needed. Here we review the available knowledge concerning the structure, function and development of the different parts of the lamprey visual system. The lamprey exhibits stepwise development of the visual system during its life cycle. In prolarvae and early larvae, the 'primary' retina does not have horizontal and amacrine cells, but does have photoreceptors, bipolar cells and ganglion cells. At this stage, the optic nerve projects mostly to the pretectum, where the dendrites of neurons in the nucleus of the medial longitudinal fasciculus (nMLF) appear to receive direct visual information and send motor outputs to the neck and trunk muscles. This simple neural circuit may generate negative phototaxis. Through the larval period, the lateral region of the retina grows again to form the 'secondary' retina and the topographic retinotectal projection of the optic nerve is formed, and at the same time, the extra-ocular muscles progressively develop. During metamorphosis, horizontal and amacrine cells differentiate for the first time, and the optic tectum expands and becomes laminated. The adult lamprey then has a sophisticated visual system for image-forming and visual decision-making. In the adult lamprey, the thalamic pathway (retina-thalamus-cortex/pallium) also transmits visual stimuli. Because the primary, simple light-detecting circuit in larval lamprey shares functional and developmental similarities with that of protochordates (amphioxus and tunicates), the visual development of the lamprey provides information regarding the evolutionary transition of the vertebrate visual system from the protochordate-type to the vertebrate-type.}, } @article {pmid29488309, year = {2018}, author = {Makart, L and Gillis, A and Hinnekens, P and Mahillon, J}, title = {A novel T4SS-mediated DNA transfer used by pXO16, a conjugative plasmid from Bacillus thuringiensis serovar israelensis.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1550-1561}, doi = {10.1111/1462-2920.14084}, pmid = {29488309}, issn = {1462-2920}, abstract = {The entomopathogenic Bacillus thuringiensis serovar israelensis displays peculiar conjugative transfer capabilities, accounted for by the large conjugative plasmid pXO16 (350 kb). The efficient and fast conjugative transfers are accompanied by a macroscopic aggregation of bacterial partners. Moreover, pXO16 has proven capable of effective mobilization and the retro-transfer of both mobilizable and 'non-mobilizable' plasmids. In this work, the aggregation phenomenon is shown to promote pXO16 transfer while not being mandatory for transfer. Transfer of pXO16 to B. thuringiensis recipient strains that do not display aggregation is observed as well, hence enlarging the previously defined host range. The use of variant calling analysis of transconjugants allowed for observation of up to 791 kb chromosomal regions mobilization. Previous analysis of pXO16 did not reveal any Type IV Secretion System (T4SS) homologs, which suggested the presence of an unusual conjugative system. A FtsK/SpOIIIE ATPase gene proved here to be necessary for conjugative transfer. Additionally, the analysis of natural restriction-modification systems in both conjugative partners gave credit to a ssDNA transfer mechanism. A 'transfer israelensis plasmid' (tip) region containing this ATPase gene was shown to code for other potential T4SS proteins, illustrating a conjugative system distantly related to the other known Gram-positive T4SSs.}, } @article {pmid29488307, year = {2018}, author = {Cao, SN and Yuan, Y and Qin, YH and Zhang, MZ and de Figueiredo, P and Li, GH and Qin, QM}, title = {The pre-rRNA processing factor Nop53 regulates fungal development and pathogenesis via mediating production of reactive oxygen species.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1531-1549}, doi = {10.1111/1462-2920.14082}, pmid = {29488307}, issn = {1462-2920}, abstract = {Botrytis cinerea is a necrotrophic plant fungal pathogen that annually causes enormous economic losses worldwide. The ribosome is an organelle for cellular protein biosynthesis. However, little is known about how the ribosome operates as a machine to mediate microbial pathogenesis. Here, we demonstrate that Nop53, a late-acting factor for 60S ribosomal subunit maturation, is crucial for the pathogen's development and virulence. BcNop53 is functionally equivalent to yeast nop53p. Complementation of BcNOP53 completely restored the growth defect of the yeast Δnop53 mutant. BcNop53 is located in nuclei and disruption of BcNOP53 also dramatically impaired pathogen growth. Deletion of BcNOP53 blocked infection structure formation and abolished virulence of the pathogen, possibly due to reduced production of reactive oxygen species. Moreover, loss of BcNOP53 impaired pathogen conidiation and stress adaptation, altered conidial and sclerotial morphology, retarded conidium and sclerotium germination as well as reduced the activities of cell-wall degradation-associated enzymes. Sclerotium production was, however, increased. Complementation with the wild-type BcNOP53 allele rescued defects found in the ΔBcnop53 mutant. Our work establishes a systematic elucidation of Nop53 in regulating microbial development and pathogenesis, provides novel insights into ribosomal processes that regulate fungal pathogenesis, and may open up new targets for addressing fungal diseases.}, } @article {pmid29488306, year = {2018}, author = {López-Lara, IM and Nogales, J and Pech-Canul, Á and Calatrava-Morales, N and Bernabéu-Roda, LM and Durán, P and Cuéllar, V and Olivares, J and Alvarez, L and Palenzuela-Bretones, D and Romero, M and Heeb, S and Cámara, M and Geiger, O and Soto, MJ}, title = {2-Tridecanone impacts surface-associated bacterial behaviours and hinders plant-bacteria interactions.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14083}, pmid = {29488306}, issn = {1462-2920}, abstract = {Surface motility and biofilm formation are behaviours which enable bacteria to infect their hosts and are controlled by different chemical signals. In the plant symbiotic alpha-proteobacterium Sinorhizobium meliloti, the lack of long-chain fatty acyl-coenzyme A synthetase activity (FadD) leads to increased surface motility, defects in biofilm development and impaired root colonization. In this study, analyses of lipid extracts and volatiles revealed that a fadD mutant accumulates 2-tridecanone (2-TDC), a methylketone (MK) known as a natural insecticide. Application of pure 2-TDC to the wild-type strain phenocopies the free-living and symbiotic behaviours of the fadD mutant. Structural features of the MK determine its ability to promote S. meliloti surface translocation, which is mainly mediated by a flagella-independent motility. Transcriptomic analyses showed that 2-TDC induces differential expression of iron uptake, redox and stress-related genes. Interestingly, this MK also influences surface motility and impairs biofilm formation in plant and animal pathogenic bacteria. Moreover, 2-TDC not only hampers alfalfa nodulation but also the development of tomato bacterial speck disease. This work assigns a new role to 2-TDC as an infochemical that affects important bacterial traits and hampers plant-bacteria interactions by interfering with microbial colonization of plant tissues.}, } @article {pmid29487989, year = {2018}, author = {Tang, Q and Qiu, L and Li, G}, title = {Baculovirus-Encoded MicroRNAs: A Brief Overview and Future Prospects.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1443-y}, pmid = {29487989}, issn = {1432-0991}, support = {31402016//National Natural Science Foundation of China/ ; 81402840//National Natural Science Foundation of China/ ; 1501070C//Postdoctoral Research in Jiangsu Province/ ; FCJJ2015028//a project supported by the Youth Foundation of Jiangsu University/ ; BK20130495//Natural Science Foundation of Jiangsu Province of China/ ; }, abstract = {MicroRNAs (miRNAs) are a class of non-coding RNAs with ∼22 nucleotides, which are able to regulate various biological processes, including the viral life cycle and host-pathogen interactions. Long primary transcripts (pri-miRNAs) are initially transcribed in nucleus, and subsequently processed by Dicer in cytoplasm to generate mature miRNAs. Baculoviruses consist of large, enveloped, insect-pathogenic viruses with a double-stranded circular DNA genome. Recent studies suggest that baculoviruses encode some miRNAs to manipulate expression regulation of host genes, whereas host modulate viral gene expression via miRNAs to limit viral infection. In the review, we will focus on the biogenesis and functions of miRNAs and the interactions between baculoviruses, insect, and miRNAs. It will be helpful to delve into the related mechanisms of BmNPV-encoded miRNAs that contribute to infection and pathogenesis.}, } @article {pmid29487988, year = {2018}, author = {Bevilacqua, L and Milan, A and Del Lupo, V and Maglione, M and Dolzani, L}, title = {Biofilms Developed on Dental Implant Titanium Surfaces with Different Roughness: Comparison Between In Vitro and In Vivo Studies.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {766-772}, pmid = {29487988}, issn = {1432-0991}, mesh = {Biofilms/*growth & development ; Biomass ; Dental Implants/*microbiology ; Healthy Volunteers ; Humans ; Microscopy, Confocal ; Mouth/microbiology ; Pseudomonas aeruginosa ; Titanium/*chemistry ; }, abstract = {Microbial biofilms developed on dental implants play a major role in perimplantitis' pathogenesis. Many studies have indicated that surface roughness is the main feature favoring biofilm development in vitro, but its actual influence in vivo has still to be confirmed. In this study, the amount of biofilm formed on differently treated titanium surfaces, showing distinct roughness, has been examined both in vivo and in vitro by Confocal Laser Scanning Microscopy. In vitro studies availed of biofilm developed by Pseudomonas aeruginosa or by salivary bacteria from volunteer donors. In vivo biofilm production was obtained by exposing titanium discs to the oral cavity of healthy volunteers. In vitro experiments showed that P. aeruginosa and, to a lesser extent, salivary bacteria produce more biomass and develop thicker biofilms on laser-treated and sandblasted titanium surfaces with respect to machined ones. In vivo experiments confirmed that bacterial colonization starts on sites of surface unevenness, but failed to disclose biomass differences among biofilms formed on surfaces with different roughness. Our study revealed that biofilm developed in vitro is more easily influenced by surface features than biofilm formed by complex communities in the mouth, where the cooperation of a variety of bacterial species and the presence of a wide range of nutrients and conditions allow bacteria to optimize substrate colonization. Therefore, quantitative differences observed in vitro among surfaces with different characteristics may not be predictive of different colonization rates in vivo.}, } @article {pmid29487400, year = {2018}, author = {}, title = {Genetics for your whole life.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {317}, doi = {10.1038/s41588-018-0072-5}, pmid = {29487400}, issn = {1546-1718}, } @article {pmid29487399, year = {2018}, author = {Han, L and Ren, C and Li, L and Li, X and Ge, J and Wang, H and Miao, YL and Guo, X and Moley, KH and Shu, W and Wang, Q}, title = {Publisher Correction: Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {768}, doi = {10.1038/s41588-018-0077-0}, pmid = {29487399}, issn = {1546-1718}, abstract = {In the version of this article originally published, the positions of Wenjie Shu and Qiang Wang in the author list were reversed and incorrect images were displayed in the HTML for Supplementary Figs. 1-12. The errors have been corrected in the HTML and PDF versions of the article.}, } @article {pmid29487366, year = {2018}, author = {Boscaro, V and Kolisko, M and Felletti, M and Vannini, C and Lynn, DH and Keeling, PJ}, title = {Publisher Correction: Parallel genome reduction in symbionts descended from closely related free-living bacteria.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {750}, doi = {10.1038/s41559-018-0484-8}, pmid = {29487366}, issn = {2397-334X}, abstract = {The Supplementary Information file originally published with this Article was missing Supplementary Figs 1-7. This has now been corrected.}, } @article {pmid29487365, year = {2018}, author = {Posth, C and Nägele, K and Colleran, H and Valentin, F and Bedford, S and Kami, KW and Shing, R and Buckley, H and Kinaston, R and Walworth, M and Clark, GR and Reepmeyer, C and Flexner, J and Maric, T and Moser, J and Gresky, J and Kiko, L and Robson, KJ and Auckland, K and Oppenheimer, SJ and Hill, AVS and Mentzer, AJ and Zech, J and Petchey, F and Roberts, P and Jeong, C and Gray, RD and Krause, J and Powell, A}, title = {Language continuity despite population replacement in Remote Oceania.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {731-740}, pmid = {29487365}, issn = {2397-334X}, support = {758967//European Research Council/International ; }, abstract = {Recent genomic analyses show that the earliest peoples reaching Remote Oceania-associated with Austronesian-speaking Lapita culture-were almost completely East Asian, without detectable Papuan ancestry. However, Papuan-related genetic ancestry is found across present-day Pacific populations, indicating that peoples from Near Oceania have played a significant, but largely unknown, ancestral role. Here, new genome-wide data from 19 ancient South Pacific individuals provide direct evidence of a so-far undescribed Papuan expansion into Remote Oceania starting ~2,500 yr BP, far earlier than previously estimated and supporting a model from historical linguistics. New genome-wide data from 27 contemporary ni-Vanuatu demonstrate a subsequent and almost complete replacement of Lapita-Austronesian by Near Oceanian ancestry. Despite this massive demographic change, incoming Papuan languages did not replace Austronesian languages. Population replacement with language continuity is extremely rare-if not unprecedented-in human history. Our analyses show that rather than one large-scale event, the process was incremental and complex, with repeated migrations and sex-biased admixture with peoples from the Bismarck Archipelago.}, } @article {pmid29487218, year = {2018}, author = {Pierret, A and Lacombe, G}, title = {Hydrologic regulation of plant rooting depth: Breakthrough or observational conundrum?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2669-E2670}, pmid = {29487218}, issn = {1091-6490}, mesh = {*Gene Expression Regulation, Plant ; Hydrology ; *Plant Roots ; }, } @article {pmid29487217, year = {2018}, author = {Fan, Y and Miguez-Macho, G and Jobbágy, EG and Jackson, RB and Otero-Casal, C}, title = {Reply to Pierret and Lacombe: Global controls on maximum rooting depths remain important.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2671-E2672}, pmid = {29487217}, issn = {1091-6490}, mesh = {*Plant Roots ; }, } @article {pmid29487216, year = {2018}, author = {Grassi, D and Howard, S and Zhou, M and Diaz-Perez, N and Urban, NT and Guerrero-Given, D and Kamasawa, N and Volpicelli-Daley, LA and LoGrasso, P and Lasmézas, CI}, title = {Identification of a highly neurotoxic α-synuclein species inducing mitochondrial damage and mitophagy in Parkinson's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2634-E2643}, pmid = {29487216}, issn = {1091-6490}, support = {R01 NS085223/NS/NINDS NIH HHS/United States ; }, mesh = {Acetyl-CoA Carboxylase/chemistry/metabolism ; Animals ; Autophagy/*drug effects ; Brain/drug effects/pathology ; Brain Chemistry ; Cell Culture Techniques ; Cells, Cultured ; Humans ; Lysosomes/metabolism ; Mice ; Mitochondria ; Mitochondrial Degradation/*drug effects ; *Neurotoxins/chemistry/metabolism/toxicity ; Oxidative Stress/drug effects ; Parkinson Disease/*metabolism ; Phosphorylation ; *alpha-Synuclein/chemistry/metabolism/toxicity ; }, abstract = {Exposure of cultured primary neurons to preformed α-synuclein fibrils (PFFs) leads to the recruitment of endogenous α-synuclein and its templated conversion into fibrillar phosphorylated α-synuclein (pα-synF) aggregates resembling those involved in Parkinson's disease (PD) pathogenesis. Pα-synF was described previously as inclusions morphologically similar to Lewy bodies and Lewy neurites in PD patients. We discovered the existence of a conformationally distinct, nonfibrillar, phosphorylated α-syn species that we named "pα-syn*." We uniquely describe the existence of pα-syn* in PFF-seeded primary neurons, mice brains, and PD patients' brains. Through immunofluorescence and pharmacological manipulation we showed that pα-syn* results from incomplete autophagic degradation of pα-synF. Pα-synF was decorated with autophagic markers, but pα-syn* was not. Western blots revealed that pα-syn* was N- and C-terminally trimmed, resulting in a 12.5-kDa fragment and a SDS-resistant dimer. After lysosomal release, pα-syn* aggregates associated with mitochondria, inducing mitochondrial membrane depolarization, cytochrome C release, and mitochondrial fragmentation visualized by confocal and stimulated emission depletion nanoscopy. Pα-syn* recruited phosphorylated acetyl-CoA carboxylase 1 (ACC1) with which it remarkably colocalized. ACC1 phosphorylation indicates low ATP levels, AMPK activation, and oxidative stress and induces mitochondrial fragmentation via reduced lipoylation. Pα-syn* also colocalized with BiP, a master regulator of the unfolded protein response and a resident protein of mitochondria-associated endoplasmic reticulum membranes that are sites of mitochondrial fission and mitophagy. Pα-syn* aggregates were found in Parkin-positive mitophagic vacuoles and imaged by electron microscopy. Collectively, we showed that pα-syn* induces mitochondrial toxicity and fission, energetic stress, and mitophagy, implicating pα-syn* as a key neurotoxic α-syn species and a therapeutic target.}, } @article {pmid29487215, year = {2018}, author = {Fenton, AK and Manuse, S and Flores-Kim, J and Garcia, PS and Mercy, C and Grangeasse, C and Bernhardt, TG and Rudner, DZ}, title = {Phosphorylation-dependent activation of the cell wall synthase PBP2a in Streptococcus pneumoniae by MacP.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2812-2817}, pmid = {29487215}, issn = {1091-6490}, support = {R01 AI083365/AI/NIAID NIH HHS/United States ; R01 GM073831/GM/NIGMS NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Cell Division ; Cell Wall/*enzymology/genetics/metabolism ; Coenzymes/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; Penicillin-Binding Proteins/genetics/*metabolism ; Phosphorylation ; Streptococcus pneumoniae/cytology/*enzymology/genetics/metabolism ; }, abstract = {Most bacterial cells are surrounded by an essential cell wall composed of the net-like heteropolymer peptidoglycan (PG). Growth and division of bacteria are intimately linked to the expansion of the PG meshwork and the construction of a cell wall septum that separates the nascent daughter cells. Class A penicillin-binding proteins (aPBPs) are a major family of PG synthases that build the wall matrix. Given their central role in cell wall assembly and importance as drug targets, surprisingly little is known about how the activity of aPBPs is controlled to properly coordinate cell growth and division. Here, we report the identification of MacP (SPD_0876) as a membrane-anchored cofactor of PBP2a, an aPBP synthase of the Gram-positive pathogen Streptococcus pneumoniae We show that MacP localizes to the division site of S. pneumoniae, forms a complex with PBP2a, and is required for the in vivo activity of the synthase. Importantly, MacP was also found to be a substrate for the kinase StkP, a global cell cycle regulator. Although StkP has been implicated in controlling the balance between the elongation and septation modes of cell wall synthesis, none of its substrates are known to modulate PG synthetic activity. Here we show that a phosphoablative substitution in MacP that blocks StkP-mediated phosphorylation prevents PBP2a activity without affecting the MacP-PBP2a interaction. Our results thus reveal a direct connection between PG synthase function and the control of cell morphogenesis by the StkP regulatory network.}, } @article {pmid29487214, year = {2018}, author = {Hammarlöf, DL and Kröger, C and Owen, SV and Canals, R and Lacharme-Lora, L and Wenner, N and Schager, AE and Wells, TJ and Henderson, IR and Wigley, P and Hokamp, K and Feasey, NA and Gordon, MA and Hinton, JCD}, title = {Role of a single noncoding nucleotide in the evolution of an epidemic African clade of Salmonella.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2614-E2623}, pmid = {29487214}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 106914/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {DNA, Bacterial/genetics ; Epidemics ; *Evolution, Molecular ; Genome, Bacterial/*genetics ; Humans ; Phylogeny ; Polymorphism, Single Nucleotide/genetics ; Salmonella Infections/*microbiology ; Salmonella typhimurium/*genetics/*pathogenicity ; Virulence/genetics ; Virulence Factors/genetics ; }, abstract = {Salmonella enterica serovar Typhimurium ST313 is a relatively newly emerged sequence type that is causing a devastating epidemic of bloodstream infections across sub-Saharan Africa. Analysis of hundreds of Salmonella genomes has revealed that ST313 is closely related to the ST19 group of S Typhimurium that cause gastroenteritis across the world. The core genomes of ST313 and ST19 vary by only ∼1,000 SNPs. We hypothesized that the phenotypic differences that distinguish African Salmonella from ST19 are caused by certain SNPs that directly modulate the transcription of virulence genes. Here we identified 3,597 transcriptional start sites of the ST313 strain D23580, and searched for a gene-expression signature linked to pathogenesis of Salmonella We identified a SNP in the promoter of the pgtE gene that caused high expression of the PgtE virulence factor in African S. Typhimurium, increased the degradation of the factor B component of human complement, contributed to serum resistance, and modulated virulence in the chicken infection model. We propose that high levels of PgtE expression by African S Typhimurium ST313 promote bacterial survival and dissemination during human infection. Our finding of a functional role for an extragenic SNP shows that approaches used to deduce the evolution of virulence in bacterial pathogens should include a focus on noncoding regions of the genome.}, } @article {pmid29487213, year = {2018}, author = {McNutt, MK and Bradford, M and Drazen, JM and Hanson, B and Howard, B and Jamieson, KH and Kiermer, V and Marcus, E and Pope, BK and Schekman, R and Swaminathan, S and Stang, PJ and Verma, IM}, title = {Transparency in authors' contributions and responsibilities to promote integrity in scientific publication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2557-2560}, pmid = {29487213}, issn = {1091-6490}, abstract = {In keeping with the growing movement in scientific publishing toward transparency in data and methods, we propose changes to journal authorship policies and procedures to provide insight into which author is responsible for which contributions, better assurance that the list is complete, and clearly articulated standards to justify earning authorship credit. To accomplish these goals, we recommend that journals adopt common and transparent standards for authorship, outline responsibilities for corresponding authors, adopt the Contributor Roles Taxonomy (CRediT) (docs.casrai.org/CRediT) methodology for attributing contributions, include this information in article metadata, and require authors to use the ORCID persistent digital identifier (https://orcid.org). Additionally, we recommend that universities and research institutions articulate expectations about author roles and responsibilities to provide a point of common understanding for discussion of authorship across research teams. Furthermore, we propose that funding agencies adopt the ORCID identifier and accept the CRediT taxonomy. We encourage scientific societies to further authorship transparency by signing on to these recommendations and promoting them through their meetings and publications programs.}, } @article {pmid29487212, year = {2018}, author = {Desikan, S and Koser, DE and Neitz, A and Monyer, H}, title = {Target selectivity of septal cholinergic neurons in the medial and lateral entorhinal cortex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2644-E2652}, pmid = {29487212}, issn = {1091-6490}, mesh = {Acetylcholine/metabolism ; Animals ; *Cholinergic Neurons/cytology/metabolism ; *Entorhinal Cortex/cytology/metabolism ; Luminescent Proteins/analysis/genetics/metabolism ; Male ; Mice ; Mice, Transgenic ; Optogenetics ; Receptors, Muscarinic/metabolism ; Receptors, Nicotinic/metabolism ; *Septal Nuclei/cytology/metabolism ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {The entorhinal cortex (EC) plays a pivotal role in processing and conveying spatial information to the hippocampus. It has long been known that EC neurons are modulated by cholinergic input from the medial septum. However, little is known as to how synaptic release of acetylcholine affects the different cell types in EC. Here we combined optogenetics and patch-clamp recordings to study the effect of cholinergic axon stimulation on distinct neurons in EC. We found dense cholinergic innervations that terminate in layer I and II (LI and LII). Light-activated stimulation of septal cholinergic projections revealed differential responses in excitatory and inhibitory neurons in LI and LII of both medial and lateral EC. We observed depolarizing responses mediated by nicotinic and muscarinic receptors primarily in putative serotonin receptor (p5HT3R)-expressing interneurons. Hyperpolarizing muscarinic receptor-mediated responses were found predominantly in excitatory cells. Additionally, some excitatory as well as a higher fraction of inhibitory neurons received mono- and/or polysynaptic GABAergic inputs, revealing that medial septum cholinergic neurons have the capacity to corelease GABA alongside acetylcholine. Notably, the synaptic effects of acetylcholine were similar in neurons of both medial and lateral EC. Taken together, our findings demonstrate that EC activity may be differentially modulated via the activation or the suppression of distinct subsets of LI and LII neurons by the septal cholinergic system.}, } @article {pmid29487211, year = {2018}, author = {Wang, W and Walmacq, C and Chong, J and Kashlev, M and Wang, D}, title = {Structural basis of transcriptional stalling and bypass of abasic DNA lesion by RNA polymerase II.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2538-E2545}, pmid = {29487211}, issn = {1091-6490}, support = {S10 OD021832/OD/NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; R01 GM102362/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {DNA/*chemistry/*genetics/metabolism ; *DNA Damage ; DNA Repair ; DNA Replication ; Mutation ; RNA Polymerase II/chemistry/genetics/*metabolism ; *Transcription, Genetic ; }, abstract = {Abasic sites are among the most abundant DNA lesions and interfere with DNA replication and transcription, but the mechanism of their action on transcription remains unknown. Here we applied a combined structural and biochemical approach for a comprehensive investigation of how RNA polymerase II (Pol II) processes an abasic site, leading to slow bypass of lesion. Encounter of Pol II with an abasic site involves two consecutive slow steps: insertion of adenine opposite a noninstructive abasic site (the A-rule), followed by extension of the 3'-rAMP with the next cognate nucleotide. Further studies provided structural insights into the A-rule: ATP is slowly incorporated into RNA in the absence of template guidance. Our structure revealed that ATP is bound to the Pol II active site, whereas the abasic site is located at an intermediate state above the Bridge Helix, a conserved structural motif that is cirtical for Pol II activity. The next extension step occurs in a template-dependent manner where a cognate substrate is incorporated, despite at a much slower rate compared with nondamaged template. During the extension step, neither the cognate substrate nor the template base is located at the canonical position, providing a structural explanation as to why this step is as slow as the insertion step. Taken together, our studies provide a comprehensive understanding of Pol II stalling and bypass of the abasic site in the DNA template.}, } @article {pmid29487210, year = {2018}, author = {Cotnoir-White, D and El Ezzy, M and Boulay, PL and Rozendaal, M and Bouvier, M and Gagnon, E and Mader, S}, title = {Monitoring ligand-dependent assembly of receptor ternary complexes in live cells by BRETFect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2653-E2662}, pmid = {29487210}, issn = {1091-6490}, support = {MOP125863//CIHR/Canada ; MOP133726//CIHR/Canada ; }, mesh = {Cytological Techniques/*methods ; Fluorescence Resonance Energy Transfer/*methods ; HEK293 Cells ; Humans ; Luminescent Proteins ; Receptors, Cytoplasmic and Nuclear/analysis/chemistry/*metabolism ; Receptors, G-Protein-Coupled/analysis/chemistry/*metabolism ; Ternary Complex Factors/analysis/chemistry/*metabolism ; }, abstract = {There is currently an unmet need for versatile techniques to monitor the assembly and dynamics of ternary complexes in live cells. Here we describe bioluminescence resonance energy transfer with fluorescence enhancement by combined transfer (BRETFect), a high-throughput technique that enables robust spectrometric detection of ternary protein complexes based on increased energy transfer from a luciferase to a fluorescent acceptor in the presence of a fluorescent intermediate. Its unique donor-intermediate-acceptor relay system is designed so that the acceptor can receive energy either directly from the donor or indirectly via the intermediate in a combined transfer, taking advantage of the entire luciferase emission spectrum. BRETFect was used to study the ligand-dependent cofactor interaction properties of the estrogen receptors ERα and ERβ, which form homo- or heterodimers whose distinctive regulatory properties are difficult to dissect using traditional methods. BRETFect uncovered the relative capacities of hetero- vs. homodimers to recruit receptor-specific cofactors and regulatory proteins, and to interact with common cofactors in the presence of receptor-specific ligands. BRETFect was also used to follow the assembly of ternary complexes between the V2R vasopressin receptor and two different intracellular effectors, illustrating its use for dissection of ternary protein-protein interactions engaged by G protein-coupled receptors. Our results indicate that BRETFect represents a powerful and versatile technique to monitor the dynamics of ternary interactions within multimeric complexes in live cells.}, } @article {pmid29487209, year = {2018}, author = {Helgeson, LA and Zelter, A and Riffle, M and MacCoss, MJ and Asbury, CL and Davis, TN}, title = {Human Ska complex and Ndc80 complex interact to form a load-bearing assembly that strengthens kinetochore-microtubule attachments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2740-2745}, pmid = {29487209}, issn = {1091-6490}, support = {P41 GM103533/GM/NIGMS NIH HHS/United States ; P01 GM105537/GM/NIGMS NIH HHS/United States ; R01 GM079373/GM/NIGMS NIH HHS/United States ; R01 GM040506/GM/NIGMS NIH HHS/United States ; F32 GM120912/GM/NIGMS NIH HHS/United States ; S10 RR026406/RR/NCRR NIH HHS/United States ; }, mesh = {Chromosome Segregation ; Humans ; Kinetochores/chemistry/*metabolism ; Microtubule-Associated Proteins/genetics/metabolism ; Microtubules/chemistry/genetics/*metabolism ; Nuclear Proteins/genetics/*metabolism ; Protein Binding ; }, abstract = {Accurate segregation of chromosomes relies on the force-bearing capabilities of the kinetochore to robustly attach chromosomes to dynamic microtubule tips. The human Ska complex and Ndc80 complex are outer-kinetochore components that bind microtubules and are required to fully stabilize kinetochore-microtubule attachments in vivo. While purified Ska complex tracks with disassembling microtubule tips, it remains unclear whether the Ska complex-microtubule interaction is sufficiently strong to make a significant contribution to kinetochore-microtubule coupling. Alternatively, Ska complex might affect kinetochore coupling indirectly, through recruitment of phosphoregulatory factors. Using optical tweezers, we show that the Ska complex itself bears load on microtubule tips, strengthens Ndc80 complex-based tip attachments, and increases the switching dynamics of the attached microtubule tips. Cross-linking mass spectrometry suggests the Ska complex directly binds Ndc80 complex through interactions between the Ska3 unstructured C-terminal region and the coiled-coil regions of each Ndc80 complex subunit. Deletion of the Ska complex microtubule-binding domain or the Ska3 C terminus prevents Ska complex from strengthening Ndc80 complex-based attachments. Together, our results indicate that the Ska complex can directly strengthen the kinetochore-microtubule interface and regulate microtubule tip dynamics by forming an additional connection between the Ndc80 complex and the microtubule.}, } @article {pmid29487208, year = {2018}, author = {Oakes, PW and Bidone, TC and Beckham, Y and Skeeters, AV and Ramirez-San Juan, GR and Winter, SP and Voth, GA and Gardel, ML}, title = {Lamellipodium is a myosin-independent mechanosensor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2646-2651}, pmid = {29487208}, issn = {1091-6490}, support = {R01 GM085087/GM/NIGMS NIH HHS/United States ; R01 GM104032/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena ; Cell Adhesion ; Cell Movement ; Extracellular Matrix/metabolism ; Mice ; Myosin Type II/*chemistry/*metabolism ; NIH 3T3 Cells ; Pseudopodia/*chemistry/*metabolism ; }, abstract = {The ability of adherent cells to sense changes in the mechanical properties of their extracellular environments is critical to numerous aspects of their physiology. It has been well documented that cell attachment and spreading are sensitive to substrate stiffness. Here, we demonstrate that this behavior is actually biphasic, with a transition that occurs around a Young's modulus of ∼7 kPa. Furthermore, we demonstrate that, contrary to established assumptions, this property is independent of myosin II activity. Rather, we find that cell spreading on soft substrates is inhibited due to reduced myosin-II independent nascent adhesion formation within the lamellipodium. Cells on soft substrates display normal leading-edge protrusion activity, but these protrusions are not stabilized due to impaired adhesion assembly. Enhancing integrin-ECM affinity through addition of Mn2+ recovers nascent adhesion assembly and cell spreading on soft substrates. Using a computational model to simulate nascent adhesion assembly, we find that biophysical properties of the integrin-ECM bond are optimized to stabilize interactions above a threshold matrix stiffness that is consistent with the experimental observations. Together, these results suggest that myosin II-independent forces in the lamellipodium are responsible for mechanosensation by regulating new adhesion assembly, which, in turn, directly controls cell spreading. This myosin II-independent mechanism of substrate stiffness sensing could potentially regulate a number of other stiffness-sensitive processes.}, } @article {pmid29487202, year = {2018}, author = {Alberts, B and Gold, BD and Martin, LL and Maxon, ME}, title = {Opinion: How to bring science and technology expertise to state governments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1952-1955}, pmid = {29487202}, issn = {1091-6490}, } @article {pmid29486796, year = {2018}, author = {Rosa, BA and Supali, T and Gankpala, L and Djuardi, Y and Sartono, E and Zhou, Y and Fischer, K and Martin, J and Tyagi, R and Bolay, FK and Fischer, PU and Yazdanbakhsh, M and Mitreva, M}, title = {Differential human gut microbiome assemblages during soil-transmitted helminth infections in Indonesia and Liberia.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {33}, doi = {10.1186/s40168-018-0416-5}, pmid = {29486796}, issn = {2049-2618}, support = {AI081803-06A1//National Institute of Allergy and Infectious Diseases/ ; GH5342//Bill and Melinda Gates Foundation/ ; U54HG003079//National Human Genome Research Institute/ ; }, abstract = {BACKGROUND: The human intestine and its microbiota is the most common infection site for soil-transmitted helminths (STHs), which affect the well-being of ~ 1.5 billion people worldwide. The complex cross-kingdom interactions are not well understood.

RESULTS: A cross-sectional analysis identified conserved microbial signatures positively or negatively associated with STH infections across Liberia and Indonesia, and longitudinal samples analysis from a double-blind randomized trial showed that the gut microbiota responds to deworming but does not transition closer to the uninfected state. The microbiomes of individuals able to self-clear the infection had more alike microbiome assemblages compared to individuals who remained infected. One bacterial taxon (Lachnospiracae) was negatively associated with infection in both countries, and 12 bacterial taxa were significantly associated with STH infection in both countries, including Olsenella (associated with reduced gut inflammation), which also significantly reduced in abundance following clearance of infection. Microbial community gene abundances were also affected by deworming. Functional categories identified as associated with STH infection included arachidonic acid metabolism; arachidonic acid is the precursor for pro-inflammatory leukotrienes that threaten helminth survival, and our findings suggest that some modulation of arachidonic acid activity in the STH-infected gut may occur through the increase of arachidonic acid metabolizing bacteria.

CONCLUSIONS: For the first time, we identify specific members of the gut microbiome that discriminate between moderately/heavily STH-infected and non-infected states across very diverse geographical regions using two different statistical methods. We also identify microbiome-encoded biological functions associated with the STH infections, which are associated potentially with STH survival strategies, and changes in the host environment. These results provide a novel insight of the cross-kingdom interactions in the human gut ecosystem by unlocking the microbiome assemblages at taxonomic, genetic, and functional levels so that advances towards key mechanistic studies can be made.}, } @article {pmid29486793, year = {2018}, author = {Jingi, AM and Noubiap, JJ and Bilong, Y and Tankeu, AT and Ebana Mvogo, C}, title = {Prevalence and determinants of comprehensive eye care in a group of patients with diabetes: a cross-sectional study in a sub-Saharan African setting.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {157}, pmid = {29486793}, issn = {1756-0500}, mesh = {Adult ; Aged ; Cameroon ; Cross-Sectional Studies ; Delivery of Health Care/*statistics & numerical data ; Diabetes Complications/*diagnosis ; Eye Diseases/*diagnosis ; Female ; Hospital Departments ; Hospitals, General ; Humans ; Male ; Middle Aged ; Prevalence ; Time Factors ; }, abstract = {OBJECTIVES: We aimed to investigate the determinants of comprehensive eye examination in diabetes patients. We conducted a cross-sectional study at the eye department of the Douala General Hospital. Adult patients with diabetes were consecutively interviewed on the history of their diabetes. Main outcomes were a first ever comprehensive eye examination including fundoscopy, and diagnosis-to-fundoscopy time.

RESULTS: 52 patients were included of whom 59.6% were males with a mean age of 55.9 ± 10.9 years. 51.9% have had counselling on the risk of visual impairment and blindness due to diabetes, and 61.5% [95% CI 47-74.7] have had a comprehensive eye examination. Of those with a first ever fundoscopy, only 21.9% had the test performed within 1 year of diagnosis. Thus, after an average of 10 years of the diagnosis of diabetes, 13.5% (7/52) of patients have had a comprehensive eye examination within 1 year of diagnosis. Only dose with duration of diabetes of more than 10 years were 7-24 times more likely to have a comprehensive eye examination. In summary, patients with diabetes in this low-income setting do not receive a comprehensive eye care as recommended. Most patients will get an eye examination at least 10 years after the diagnosis of diabetes.}, } @article {pmid29486745, year = {2018}, author = {Navarro, G and Cordomí, A and Brugarolas, M and Moreno, E and Aguinaga, D and Pérez-Benito, L and Ferre, S and Cortés, A and Casadó, V and Mallol, J and Canela, EI and Lluís, C and Pardo, L and McCormick, PJ and Franco, R}, title = {Cross-communication between Gi and Gs in a G-protein-coupled receptor heterotetramer guided by a receptor C-terminal domain.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {24}, doi = {10.1186/s12915-018-0491-x}, pmid = {29486745}, issn = {1741-7007}, support = {Intramural/DA/NIDA NIH HHS/United States ; }, abstract = {BACKGROUND: G-protein-coupled receptor (GPCR) heteromeric complexes have distinct properties from homomeric GPCRs, giving rise to new receptor functionalities. Adenosine receptors (A1R or A2AR) can form A1R-A2AR heteromers (A1-A2AHet), and their activation leads to canonical G-protein-dependent (adenylate cyclase mediated) and -independent (β-arrestin mediated) signaling. Adenosine has different affinities for A1R and A2AR, allowing the heteromeric receptor to detect its concentration by integrating the downstream Gi- and Gs-dependent signals. cAMP accumulation and β-arrestin recruitment assays have shown that, within the complex, activation of A2AR impedes signaling via A1R.

RESULTS: We examined the mechanism by which A1-A2AHet integrates Gi- and Gs-dependent signals. A1R blockade by A2AR in the A1-A2AHet is not observed in the absence of A2AR activation by agonists, in the absence of the C-terminal domain of A2AR, or in the presence of synthetic peptides that disrupt the heteromer interface of A1-A2AHet, indicating that signaling mediated by A1R and A2AR is controlled by both Gi and Gs proteins.

CONCLUSIONS: We identified a new mechanism of signal transduction that implies a cross-communication between Gi and Gs proteins guided by the C-terminal tail of the A2AR. This mechanism provides the molecular basis for the operation of the A1-A2AHet as an adenosine concentration-sensing device that modulates the signals originating at both A1R and A2AR.}, } @article {pmid29486740, year = {2018}, author = {Yu, P and Nie, Q and Tang, C and Zhang, L}, title = {Nanog induced intermediate state in regulating stem cell differentiation and reprogramming.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {22}, doi = {10.1186/s12918-018-0552-3}, pmid = {29486740}, issn = {1752-0509}, support = {91430217//National Natural Science Foundation of China/ ; 11622102//National Natural Science Foundation of China/ ; 91430217//National Natural Science Foundation of China/ ; 11421110001//National Natural Science Foundation of China/ ; 2015CB910300//Ministry of Science and Technology of the People's Republic of China/ ; DMS1562176//National Science Foundation/ ; P50GM076516//National Institutes of Health/ ; R01GM107264//National Institutes of Health/ ; R01NS095355//National Institutes of Health/ ; }, abstract = {BACKGROUND: Heterogeneous gene expressions of cells are widely observed in self-renewing pluripotent stem cells, suggesting possible coexistence of multiple cellular states with distinct characteristics. Though the elements regulating cellular states have been identified, the underlying dynamic mechanisms and the significance of such cellular heterogeneity remain elusive.

RESULTS: We present a gene regulatory network model to investigate the bimodal Nanog distribution in stem cells. Our model reveals a novel role of dynamic conversion between the cellular states of high and low Nanog levels. Model simulations demonstrate that the low-Nanog state benefits cell differentiation through serving as an intermediate state to reduce the barrier of transition. Interestingly, the existence of low-Nanog state dynamically slows down the reprogramming process, and additional Nanog activation is found to be essential to quickly attaining the fully reprogrammed cell state.

CONCLUSIONS: Nanog has been recognized as a critical pluripotency gene in stem cell regulation. Our modeling results quantitatively show a dual role of Nanog during stem cell differentiation and reprogramming, and the importance of the intermediate state during cell state transitions. Our approach offers a general method for analyzing key regulatory factors controlling cell differentiation and reprogramming.}, } @article {pmid29486732, year = {2018}, author = {Nicolini, P and Amorín, R and Han, Y and Peñagaricano, F}, title = {Whole-genome scan reveals significant non-additive effects for sire conception rate in Holstein cattle.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {14}, pmid = {29486732}, issn = {1471-2156}, abstract = {BACKGROUND: Service sire has a considerable impact on reproductive success in dairy cattle. Most gene mapping studies for bull fertility have focused on additive effects, while non-additive effects have been largely ignored. The main goal of this study was to assess the relevance of non-additive effects on Sire Conception Rate (SCR) in Holstein dairy cattle. The analysis included 7.5 k Holstein bulls with both SCR records and 57.8 k single nucleotide polymorphism (SNP) markers spanning the entire genome.

RESULTS: The importance of non-additive effects was evaluated using an efficient two-step mixed model-based approach. Four genomic regions located on chromosomes BTA8, BTA9, BTA13 and BTA17 showed marked dominance and/or recessive effects. Most of these regions harbor genes, such as ADAM28, DNAJA1, TBC1D20, SPO11, PIWIL3 and TMEM119, that are directly implicated in testis development, male germ line maintenance, and sperm maturation.

CONCLUSIONS: This study provides further evidence for the relevance of non-additive effects in fitness-related traits, such as male fertility. In addition, these findings may point out new strategies for improving service sire fertility in dairy cattle via marker-assisted selection.}, } @article {pmid29486721, year = {2018}, author = {Zhang, JY and Zhang, LP and Yu, DN and Storey, KB and Zheng, RQ}, title = {Complete mitochondrial genomes of Nanorana taihangnica and N. yunnanensis (Anura: Dicroglossidae) with novel gene arrangements and phylogenetic relationship of Dicroglossidae.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {26}, doi = {10.1186/s12862-018-1140-2}, pmid = {29486721}, issn = {1471-2148}, support = {LQ16C030001//Natural Science Foundation of Zhejiang Province/International ; 31472015//National Natural Science Foundation of China (CN)/International ; 31370042//National Natural Science Foundation of China (CN)/International ; 2014C32068//the Science Technology Commission of Zhejiang Province/International ; }, mesh = {Animals ; Anura/*genetics ; Base Sequence ; DNA, Mitochondrial/genetics ; Gene Order ; *Gene Rearrangement ; Genes, Mitochondrial ; *Genome, Mitochondrial ; Nucleic Acid Conformation ; *Phylogeny ; Phylogeography ; RNA, Transfer/genetics ; }, abstract = {BACKGROUND: Complete mitochondrial (mt) genomes have been used extensively to test hypotheses about microevolution and to study population structure, phylogeography, and phylogenetic relationships of Anura at various taxonomic levels. Large-scale mt genomic reorganizations have been observed among many fork-tongued frogs (family Dicroglossidae). The relationships among Dicroglossidae and validation of the genus Feirana are still problematic. Hence, we sequenced the complete mt genomes of Nanorana taihangnica (=F. taihangnica) and N. yunnanensis as well as partial mt genomes of six Quasipaa species (dicroglossid taxa), two Odorrana and two Amolops species (Ranidae), and one Rhacophorus species (Rhacophoridae) in order to identify unknown mt gene rearrangements, to investigate the validity of the genus Feirana, and to test the phylogenetic relationship of Dicroglossidae.

RESULTS: In the mt genome of N. taihangnica two trnM genes, two trnP genes and two control regions were found. In addition, the trnA, trnN, trnC, and trnQ genes were translocated from their typical positions. In the mt genome of N. yunnanensis, three control regions were found and eight genes (ND6, trnP, trnQ, trnA, trnN, trnC, trnY and trnS genes) in the L-stand were translocated from their typical position and grouped together. We also found intraspecific rearrangement of the mitochondrial genomes in N. taihangnica and Quasipaa boulengeri. In phylogenetic trees, the genus Feirana nested deeply within the clade of genus Nanorana, indicating that the genus Feirana may be a synonym to Nanorana. Ranidae as a sister clade to Dicroglossidae and the clade of (Ranidae + Dicroglossidae) as a sister clade to (Mantellidae + Rhacophoridae) were well supported in BI analysis but low bootstrap in ML analysis.

CONCLUSIONS: We found that the gene arrangements of N. taihangnica and N. yunnanensis differed from other published dicroglossid mt genomes. The gene arrangements in N. taihangnica and N. yunnanensis could be explained by the Tandem Duplication and Random Loss (TDRL) and the Dimer-Mitogenome and Non-Random Loss (DMNR) models, respectively. The invalidation of the genus Feirana is supported in this study.}, } @article {pmid29486719, year = {2018}, author = {Li, Q and Peng, T and Klug, G}, title = {The PhyR homolog RSP_1274 of Rhodobacter sphaeroides is involved in defense of membrane stress and has a moderate effect on RpoE (RSP_1092) activity.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {18}, pmid = {29486719}, issn = {1471-2180}, abstract = {BACKGROUND: A major role of the PhyR-NepR-σ(EcfG) cascade in the general stress response was demonstrated for some bacterial species and considered as conserved in Alphaproteobacteria. The σ(EcfG) factor activates its target genes in response to diverse stresses and NepR represents its anti-sigma factor. PhyR comprises a response regulator domain and a sigma factor domain and acts as anti-sigma factor antagonist. The facultative phototrophic alphaproteobacterium Rhodobacter sphaeroides harbours a PhyR homolog in the same genomic context as found in other members of this class.

RESULTS: Our study reveals increased expression of the phyR gene in response to superoxide, singlet oxygen, and diamide and also an effect of PhyR on rpoE expression. RpoE has a central role in mounting the response to singlet oxygen in R. sphaeroides. Despite these findings a mutant lacking PhyR was not significantly impeded in resistance to oxidative stress, heat stress or osmotic stress. However a role of PhyR in membrane stress is demonstrated.

CONCLUSION: These results support the view that the effect of the PhyR-NepR-σ(EcfG) cascade on diverse stress responses varies among members of the Alphaproteobacteria. In the facultative phototroph Rhodobacter sphaeroides PhyR plays no major role in the general stress or the oxidative stress response but rather has a more specialized role in defense of membrane stress.}, } @article {pmid29486711, year = {2018}, author = {Ziyatdinov, A and Vázquez-Santiago, M and Brunel, H and Martinez-Perez, A and Aschard, H and Soria, JM}, title = {lme4qtl: linear mixed models with flexible covariance structure for genetic studies of related individuals.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {68}, pmid = {29486711}, issn = {1471-2105}, support = {R21 HG007687/HG/NHGRI NIH HHS/United States ; PI 14/0582//Instituto de Salud Carlos III Fondo de Investigación Sanitaria/International ; R21HG007687/NH/NIH HHS/United States ; }, mesh = {*Genome-Wide Association Study ; Humans ; Linear Models ; *Models, Genetic ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; *Software ; Thrombophilia/genetics ; }, abstract = {BACKGROUND: Quantitative trait locus (QTL) mapping in genetic data often involves analysis of correlated observations, which need to be accounted for to avoid false association signals. This is commonly performed by modeling such correlations as random effects in linear mixed models (LMMs). The R package lme4 is a well-established tool that implements major LMM features using sparse matrix methods; however, it is not fully adapted for QTL mapping association and linkage studies. In particular, two LMM features are lacking in the base version of lme4: the definition of random effects by custom covariance matrices; and parameter constraints, which are essential in advanced QTL models. Apart from applications in linkage studies of related individuals, such functionalities are of high interest for association studies in situations where multiple covariance matrices need to be modeled, a scenario not covered by many genome-wide association study (GWAS) software.

RESULTS: To address the aforementioned limitations, we developed a new R package lme4qtl as an extension of lme4. First, lme4qtl contributes new models for genetic studies within a single tool integrated with lme4 and its companion packages. Second, lme4qtl offers a flexible framework for scenarios with multiple levels of relatedness and becomes efficient when covariance matrices are sparse. We showed the value of our package using real family-based data in the Genetic Analysis of Idiopathic Thrombophilia 2 (GAIT2) project.

CONCLUSIONS: Our software lme4qtl enables QTL mapping models with a versatile structure of random effects and efficient computation for sparse covariances. lme4qtl is available at https://github.com/variani/lme4qtl .}, } @article {pmid29486709, year = {2018}, author = {Olsen, LC and Kourtesis, I and Busengdal, H and Jensen, MF and Hausen, H and Chourrout, D}, title = {Evidence for a centrosome-attracting body like structure in germ-soma segregation during early development, in the urochordate Oikopleura dioica.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {4}, pmid = {29486709}, issn = {1471-213X}, support = {234817//Norges Forskningsråd/International ; }, abstract = {BACKGROUND: Germ cell formation has been investigated in sessile forms of tunicates. This process involves the release of a subset of maternal transcripts from the centrosome-attracting body (CAB) in the progenitor cells of the germ line. When germ-soma segregation is completed, CAB structures are missing from the newly formed primordial germ cells (PGCs). In free-swimming tunicates, knowledge about germ cell formation is lacking. In this investigation, comparative gene expression and electron microscopy studies were used to address germ cell formation in Oikopleura dioica (O. dioica).

RESULTS: We found that the RNA localization pattern of pumilio (pum1) is similar to the pattern described for a subset of maternal transcripts marking the posterior end of ascidian embryos. Transcripts marking the posterior end are called postplasmic or posterior-end mark (PEM) transcripts. We found no localization of vasa (vas) transcripts to any sub-region within the germ-line precursor cells. Expression of vas4 was detected in the newly formed PGCs. Electron microscopy studies confirmed the presence of structures with similar morphology to CAB. In the same cytoplasmic compartment, we also identified pum1 transcripts and an epitope recognized by an antibody to histone H3 phosphorylated on serine 28.

CONCLUSIONS: Our findings support that a CAB-like structure participates in the segregation of maternal pum1 transcripts during germ-soma separation in O. dioica.}, } @article {pmid29486237, year = {2018}, author = {De-la-Mora, M and Piñero, D and Oyama, K and Farrell, B and Magallón, S and Núñez-Farfán, J}, title = {Evolution of Trichobaris (Curculionidae) in relation to host plants: Geometric morphometrics, phylogeny and phylogeography.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {37-49}, doi = {10.1016/j.ympev.2018.02.018}, pmid = {29486237}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Calibration ; Electron Transport Complex IV/genetics ; Genetic Variation ; Geography ; Haplotypes/genetics ; *Host-Parasite Interactions ; *Phylogeny ; *Phylogeography ; Plants/*parasitology ; RNA, Ribosomal, 16S/genetics ; Species Specificity ; Weevils/*anatomy & histology/*classification/genetics ; }, abstract = {The family Curculionidae (Coleoptera), the "true" weevils, have diversified tightly linked to the evolution of flowering plants. Here, we aim to assess diversification at a lower taxonomic level. We analyze the evolution of the genus Trichobaris in association with their host plants. Trichobaris comprises eight to thirteen species; their larvae feed inside the fruits of Datura spp. or inside the stem of wild and cultivated species of Solanaceae, such as potato, tobacco and tomato. We ask the following questions: (1) does the rostrum of Trichobaris species evolve according to the plant tissue used to oviposit, i.e., shorter rostrum to dig in stems and longer to dig in fruits? and (2) does Trichobaris diversify mainly in relation to the use of Datura species? For the first question, we estimated the phylogeny of Trichobaris based on four gene sequences (nuclear 18S and 28S rRNA genes and mitochondrial 16S rRNA and COI genes). Then, we carried out morphogeometric analyses of the Trichobaris species using 75 landmarks. For the second question, we calibrated a COI haplotype phylogeny using a constant rate of divergence to infer the diversification time of Trichobaris species, and we traced the host plant species on the haplotype network. We performed an ancestral state reconstruction analysis to infer recent colonization events and conserved associations with host plant species. We found that ancestral species in the Trichobaris phylogeny use the stem of Solanum plants for oviposition and display weak sexual dimorphism of rostrum size, whereas other, more recent species of Trichobaris display sexual dimorphism in rostrum size and use the fruits of Datura species, and a possible reversion to use the stem of Solanaceae was detected in one Trichobaris species. The use of Datura species by Trichobaris species is widely distributed on haplotype networks and restricted to Trichobaris species that originated ca. 5 ± 1.5 Ma. Given that the origin of Trichobaris is estimated to be ca. 6 ± 1.5 Ma, it is likely that Datura has played a role in its diversification.}, } @article {pmid29486153, year = {2018}, author = {Lacomme, M and Medevielle, F and Bourbon, HM and Thierion, E and Kleinjan, DJ and Roussat, M and Pituello, F and Bel-Vialar, S}, title = {A long range distal enhancer controls temporal fine-tuning of PAX6 expression in neuronal precursors.}, journal = {Developmental biology}, volume = {436}, number = {2}, pages = {94-107}, doi = {10.1016/j.ydbio.2018.02.015}, pmid = {29486153}, issn = {1095-564X}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/metabolism ; Chick Embryo ; Enhancer Elements, Genetic/*genetics ; Gene Expression Regulation, Developmental ; Immunohistochemistry ; In Situ Hybridization ; Mice ; Nerve Tissue Proteins/metabolism ; Neural Tube/embryology/*metabolism ; Neurogenesis/*genetics ; PAX6 Transcription Factor/*metabolism ; Receptors, Retinoic Acid/metabolism ; Signal Transduction/physiology ; Zebrafish ; }, abstract = {Proper embryonic development relies on a tight control of spatial and temporal gene expression profiles in a highly regulated manner. One good example is the ON/OFF switching of the transcription factor PAX6 that governs important steps of neurogenesis. In the neural tube PAX6 expression is initiated in neural progenitors through the positive action of retinoic acid signaling and downregulated in neuronal precursors by the bHLH transcription factor NEUROG2. How these two regulatory inputs are integrated at the molecular level to properly fine tune temporal PAX6 expression is not known. In this study we identified and characterized a 940-bp long distal cis-regulatory module (CRM), located far away from the PAX6 transcription unit and which conveys positive input from RA signaling pathway and indirect repressive signal(s) from NEUROG2. These opposing regulatory signals are integrated through HOMZ, a 94 bp core region within E940 which is evolutionarily conserved in distant organisms such as the zebrafish. We show that within HOMZ, NEUROG2 and RA exert their opposite temporal activities through a short 60 bp region containing a functional RA-responsive element (RARE). We propose a model in which retinoic acid receptors (RARs) and NEUROG2 repressive target(s) compete on the same DNA motif to fine tune temporal PAX6 expression during the course of spinal neurogenesis.}, } @article {pmid29485400, year = {2018}, author = {Sakai, HD and Kurosawa, N}, title = {Saccharolobus caldissimus gen. nov., sp. nov., a facultatively anaerobic iron-reducing hyperthermophilic archaeon isolated from an acidic terrestrial hot spring, and reclassification of Sulfolobus solfataricus as Saccharolobus solfataricus comb. nov. and Sulfolobus shibatae as Saccharolobus shibatae comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1271-1278}, doi = {10.1099/ijsem.0.002665}, pmid = {29485400}, issn = {1466-5034}, mesh = {Chemoautotrophic Growth ; DNA, Archaeal/genetics ; Hot Springs/*microbiology ; Iron/metabolism ; Japan ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sulfolobus/*classification/genetics/isolation & purification ; Sulfolobus solfataricus/*classification ; }, abstract = {A novel hyperthermophilic archaeon of strain HS-3T, belonging to the family Sulfolobaceae, was isolated from an acidic terrestrial hot spring in Hakone Ohwaku-dani, Japan. Based on 16S rRNA gene sequence analysis, the closest phylogenetic relatives of strain HS-3T were, first, Sulfolobus solfataricus (96.4 %) and, second, Sulfolobus shibatae (96.2 %), indicating that the strain belongs to the genus Sulfolobus. However, the sequence similarity to the type species of the genus Sulfolobus (Sulfolobus acidocaldarius) was remarkably low (91.8 %). In order to determine whether strain HS-3T belongs to the genus Sulfolobus, its morphological, biochemical and physiological characteristics were examined in parallel with those of S. solfataricus and S. shibatae. Although there were some differences in chemolithotrophic growth between strain HS-3T, S. solfataricus and S. shibatae, their temperature, pH and facultatively anaerobic characteristics of growth, and their utilization of various sugars were almost identical. In contrast, the utilization of various sugars by S. acidocaldarius was quite different from that of HS-3T, S. solfataricus and S. shibatae. Phylogenetic evidence based on the 16S and the 23S rRNA gene sequences also clearly distinguished the monophyletic clade composed of strain HS-3T, S. solfataricus, and S. shibatae from S. acidocaldarius. Based on these results, we propose a new genus and species, Saccharolobus caldissimus gen. nov., sp. nov., for strain HS-3T, as well as two reclassifications, Saccharolobus solfataricus comb. nov. and Saccharolobus shibatae comb. nov. The type strain of Saccharolobus caldissimus is HS-3T (=JCM 32116T and InaCC Ar80T). The type species of the genus is Saccharolobus solfataricus.}, } @article {pmid29485399, year = {2018}, author = {Zhang, YG and Wang, HF and Alkhalifah, DHM and Xiao, M and Zhou, XK and Liu, YH and Hozzein, WN and Li, WJ}, title = {Glycomyces anabasis sp. nov., a novel endophytic actinobacterium isolated from roots of Anabasis aphylla L.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1285-1290}, doi = {10.1099/ijsem.0.002668}, pmid = {29485399}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; Chenopodiaceae/*microbiology ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {A novel endophytic actinobacterium, designated strain EGI 6500139T, was isolated from the surface-sterilized roots of Anabasis aphylla L., collected from Xinjiang, northwest PR China, and subjected to polyphasic taxonomic characterization. Strain EGI 6500139T formed sparse aerial mycelium with rod-like spores. Whole-cell hydrolysates of the isolate contained meso-diaminopimelic acid as the cell-wall diamino acid, glucose as major sugar, and mannose, galactose, xylose and ribose as minor sugars. The polar lipids were phosphatidylglycerol, diphosphatidylglycerol, phosphatidylinositol, phosphatidylinositol mannoside, one unidentified glycolipid, one unidentified phospholipid and four unidentified polar lipids. The major fatty acids identified were anteiso-C17 : 0, anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0. The predominant menaquinones detected were MK-11 and MK-11(H2). The G+C content of the genomic DNA of strain EGI 6500139T was 70.4 mol%. Strain EGI 6500139T showed the highest 16S rRNA gene sequence similarity to Glycomyces lacisalsi XHU 5089T (96.3 %). Phylogenetic analysis showed that strain EGI 6500139T fell within the clade of the genus Glycomyces, and formed a clade with G. lacisalsi XHU 5089T and G. albus CCTCC AA 2013004T. Based on phenotypic, chemotaxonomic and phylogenetic data, strain EGI 6500139T represents a novel species of the genus Glycomyces, for which the name Glycomyces anabasis sp. nov. (type strain EGI 6500139T=JCM 30088T=KCTC 29495T) is proposed.}, } @article {pmid29485397, year = {2018}, author = {Fan, MC and Guo, YQ and Zhang, LP and Zhu, YM and Chen, WM and Lin, YB and Wei, GH}, title = {Herbaspirillum robiniae sp. nov., isolated from root nodules of Robinia pseudoacacia in a lead-zinc mine.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1300-1306}, doi = {10.1099/ijsem.0.002666}, pmid = {29485397}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Herbaspirillum/*cytology/genetics/isolation & purification ; Lead ; Mining ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Robinia/*microbiology ; Root Nodules, Plant/*microbiology ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; Zinc ; }, abstract = {A novel endophytic bacterium, designated strain HZ10T, was isolated from root nodules of Robinia pseudoacacia growing in a lead-zinc mine in Mianxian County, Shaanxi Province, China. The bacterium was Gram-stain-negative, aerobic, motile, slightly curved- and rod-shaped, methyl red-negative, catalase-positive, and did not produce H2S. Strain HZ10T grew at 4-45 °C (optimum, 25-30 °C), pH 5-9 (optimum, pH 7-8) and 0-1 % (w/v) NaCl. The major fatty acids were identified as C16 : 0, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), and the quinone type was Q-8. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The DNA G+C content of the genomic DNA was 64.9 mol% based on the whole genome sequence. According to the 16S rRNA gene sequence analysis, the closest phylogenetic relative to strain HZ10T is Herbaspirillum chlorophenolicum CPW301T (98.72 % sequence identity). Genome relatedness of the type strains H. chlorophenolicum CPW301T, Herbaspirillum seropedicae Z67T and Herbaspirillum aquaticum IEH 4430T, was quantified by using the average nucleotide identity (86.9-88.0 %) and a genome-to-genome distance analysis (26.6 %-29.3 %), with both strongly supporting the notion that strain HZ10T belongs to the genus Herbaspirillum as a novel species. Based on the results from phylogenetic, chemotaxonomic and physiological analyses, strain HZ10T represents a novel Herbaspirillum species, for which the name Herbaspirillum robiniae sp. nov. is proposed. The type strain is HZ10T (=JCM 31754T=CCTCC AB 2014352T).}, } @article {pmid29485396, year = {2018}, author = {Chaudhary, DK and Dahal, RH and Oren, A and Kim, J}, title = {Proposal of Nemorincola gen. nov. to replace the illegitimate prokaryotic genus name Nemorella Chaudhary et al. 2018.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002673}, pmid = {29485396}, issn = {1466-5034}, abstract = {The prokaryotic genus name Nemorella Chaudhary et al. 2018 is illegitimate because it is a later homonym of the plant genus name Nemorella Ehrhart 1789 [Principle 2 of the Prokaryotic Code (2008 Revision)]. This name is therefore not a correct name (Principle 6). Based on Rule 54 we propose the replacement name Nemorincola with Nemorincola caseinilytica as the type species.}, } @article {pmid29485394, year = {2018}, author = {Palmer, M and Steenkamp, ET and Coetzee, MPA and Avontuur, JR and Chan, WY and van Zyl, E and Blom, J and Venter, SN}, title = {Mixta gen. nov., a new genus in the Erwiniaceae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1396-1407}, doi = {10.1099/ijsem.0.002540}, pmid = {29485394}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Enterobacteriaceae/*classification/genetics/isolation & purification ; Genes, Bacterial ; Multilocus Sequence Typing ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The Erwiniaceae contain many species of agricultural and clinical importance. Although relationships among most of the genera in this family are relatively well resolved, the phylogenetic placement of several taxa remains ambiguous. In this study, we aimed to address these uncertainties by using a combination of phylogenetic and genomic approaches. Our multilocus sequence analysis and genome-based maximum-likelihood phylogenies revealed that the arsenate-reducing strain IMH and plant-associated strain ATCC 700886, both previously presumptively identified as members of Pantoea, represent novel species of Erwinia. Our data also showed that the taxonomy of Erwinia teleogrylli requires revision as it is clearly excluded from Erwinia and the other genera of the family. Most strikingly, however, five species of Pantoea formed a distinct clade within the Erwiniaceae, where it had a sister group relationship with the Pantoea + Tatumella clade. By making use of gene content comparisons, this new clade is further predicted to encode a range of characters that it shares with or distinguishes it from related genera. We thus propose recognition of this clade as a distinct genus and suggest the name Mixta in reference to the diverse habitats from which its species were obtained, including plants, humans and food products. Accordingly, a description for Mixta gen. nov. is provided to accommodate the four species Mixta calida comb. nov., M. gaviniae comb. nov., M. intestinalis comb. nov. and M. theicola comb. nov., with M. calida as the type species for the genus.}, } @article {pmid29485392, year = {2018}, author = {Cai, H and Zeng, Y and Wang, Y and Cui, H and Jiang, H}, title = {Flavobacterium cyanobacteriorum sp. nov., isolated from cyanobacterial aggregates in a eutrophic lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1279-1284}, doi = {10.1099/ijsem.0.002664}, pmid = {29485392}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A Gram-reaction-negative, aerobic, non-flagellated, non-gliding, rod-shaped and yellow-pigmented bacterium, designated strain TH021T, was isolated from cyanobacterial aggregates in a eutrophic lake, Taihu Lake, China. Optimal growth occurred at pH 7.0 (range: 5.0-10.0), 28 °C (range, 4-32 °C) and 0 % (w/v) NaCl (range, 0-1.0 %) in Reasoner's 2A broth. No growth was observed at 37 °C. The cells were found to be positive for oxidase and catalase activities. The major respiratory quinone was menaquinone-6. The major fatty acids (>10 %) were identified as iso-C15 : 0 and C16 : 1ω7c/C16 : 1ω6c. The major polar lipid was phosphatidylethanolamine. Phylogenetic analysis based on 16S rRNA gene sequences revealed that the isolate was affiliated with the genus Flavobacterium, with the highest sequence similarity found to Flavobacterium hauense BX12T (94.92 %), followed by Flavobacterium suzhouense XIN-1T (94.85 %), Flavobacterium arcticum SM1502T (94.79 %) and Flavobacterium beibuense F44-8T (94.30 %). The genomic G+C content of strain TH021T was 41.9 mol% based on total genome calculations. Average nucleotide identities and digital DNA-DNA hybridizations values for complete genomes ranged from 69.4 to 72.8 and 18.0 to 23.8 % between strain TH021T and strains within the genus Flavobacterium. The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis suggested that strain TH021T represents a novel species within the genus Flavobacterium, for which the name Flavobacterium cyanobacteriorum sp. nov. is proposed. The type strain is TH021T (=LMG 29720T=CGMCC 1.16325T).}, } @article {pmid29485391, year = {2018}, author = {Thawai, C}, title = {Pseudonocardia soli sp. nov., isolated from mountain soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1307-1312}, doi = {10.1099/ijsem.0.002672}, pmid = {29485391}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, designated strain NW8-21T, was isolated from mountain soil in Mae-Wong National Park, Nakornsawan province, Thailand, and was taxonomically characterized by using a polyphasic approach. Based on 16S rRNA gene sequence analysis, the strain was revealed to have the closest similarity to Pseudonocardia endophytica YIM 56035T with the highest 16S rRNA gene sequence similarity value of 98.7 %, followed by Pseudonocardia nantongensis KLBMP 1282T (98.0 %). The chemotaxonomic properties, i.e. arabinose and galactose as the diagnostic reducing sugar in cells, MK-8 (H4) as a major menaquinone, iso-C16 : 0 as the main cellular fatty acid component and phosphatidylethanolamine, phosphatidylmethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol, phosphatidylcholine as the characteristic phospholipids, confirmed a taxonomic affiliation of the strain that was consistent with those of the genus Pseudonocardia. Several phenotypic differences and the DNA-DNA hybridization results (less than 40 % relatedness value) indicated that strain NW8-21T shoud be considered to represent a novel species of the genus Pseudonocardia, for which the name Pseudonocardia soli is proposed. The type strain is strain NW8-21T (=BCC 58125T=NBRC 109519T).}, } @article {pmid29485239, year = {2018}, author = {Tóth, Z and Hettyey, A}, title = {Egg-laying environment modulates offspring responses to predation risk in an amphibian.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {710-721}, doi = {10.1111/jeb.13258}, pmid = {29485239}, issn = {1420-9101}, abstract = {Predator-induced plasticity has been in the focus of evolutionary ecological research in the last decades, but the consequences of temporal variation in the presence of cues predicting offspring environment have remained controversial. This is partly due to the fact that the role of early environmental effects has scarcely been scrutinized in this context while also controlling for potential maternal effects. In this study, we investigated how past environmental conditions, that is different combinations of risky or safe adult (prenatal) and oviposition (early post-natal) environments, affected offspring's plastic responses in hatching time and locomotor activity to predation risk during development in the smooth newt (Lissotriton vulgaris). We found that females did not adjust their reproductive investment to the perceived level of risk in the adult environment, and this prenatal environment had generally negligible effect on offspring phenotype. However, when predator cues were absent during oviposition, larvae raised in the presence of predator cues delayed their hatching and exhibited a decreased activity compared to control larvae developing without predator cues, which responses are advantageous when predators pose a threat to hatched larvae. In the presence of predator cues during oviposition, the difference in hatching time persisted, but the difference in general locomotor activity disappeared between risk-exposed and control larvae. Our findings provide clear experimental evidence that fine-scale temporal variation in a predictive cue during and after egg-laying interactively affects offspring phenotype, and highlight the importance of the early post-natal environment, which may exert a substantial influence on progeny's phenotype also under natural conditions.}, } @article {pmid29485222, year = {2018}, author = {Morrison, ES and Badyaev, AV}, title = {Structure versus time in the evolutionary diversification of avian carotenoid metabolic networks.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {764-772}, doi = {10.1111/jeb.13257}, pmid = {29485222}, issn = {1420-9101}, abstract = {Historical associations of genes and proteins are thought to delineate pathways available to subsequent evolution; however, the effects of past functional involvements on contemporary evolution are rarely quantified. Here, we examined the extent to which the structure of a carotenoid enzymatic network persists in avian evolution. Specifically, we tested whether the evolution of carotenoid networks was most concordant with phylogenetically structured expansion from core reactions of common ancestors or with subsampling of biochemical pathway modules from an ancestral network. We compared structural and historical associations in 467 carotenoid networks of extant and ancestral species and uncovered the overwhelming effect of pre-existing metabolic network structure on carotenoid diversification over the last 50 million years of avian evolution. Over evolutionary time, birds repeatedly subsampled and recombined conserved biochemical modules, which likely maintained the overall structure of the carotenoid metabolic network during avian evolution. These findings explain the recurrent convergence of evolutionary distant species in carotenoid metabolism and weak phylogenetic signal in avian carotenoid evolution. Remarkable retention of an ancient metabolic structure throughout extensive and prolonged ecological diversification in avian carotenoid metabolism illustrates a fundamental requirement of organismal evolution - historical continuity of a deterministic network that links past and present functional associations of its components.}, } @article {pmid29485191, year = {2018}, author = {Charles Deeming, D and Mayr, G}, title = {Pelvis morphology suggests that early Mesozoic birds were too heavy to contact incubate their eggs.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {701-709}, doi = {10.1111/jeb.13256}, pmid = {29485191}, issn = {1420-9101}, abstract = {Numerous new fossils have driven an interest in reproduction of early birds, but direct evidence remains elusive. No Mesozoic avian eggs can be unambiguously assigned to a species, which hampers our understanding of the evolution of contact incubation, which is a defining feature of extant birds. Compared to living species, eggs of Mesozoic birds are relatively small, but whether the eggs of Mesozoic birds could actually have borne the weight of a breeding adult has not yet been investigated. We estimated maximal egg breadth for a range of Mesozoic avian taxa from the width of the pelvic canal defined by the pubic symphysis. Known elongation ratios of Mesozoic bird eggs allowed us to predict egg mass and hence the load mass an egg could endure before cracking. These values were compared to the predicted body masses of the adult birds based on skeletal remains. Based on 21 fossil species, we show that for nonornithothoracine birds body mass was 187% of the load mass of the eggs. For Enantiornithes, body mass was 127% greater than the egg load mass, but some early Cretaceous ornithuromorphs were 179% heavier than their eggs could support. Our indirect approach provides the best evidence yet that early birds could not have sat on their eggs without running the risk of causing damage. We suggest that contact incubation evolved comparatively late in birds.}, } @article {pmid29484449, year = {2018}, author = {Kesmen, Z and Büyükkiraz, ME and Özbekar, E and Çelik, M and Özkök, FÖ and Kılıç, Ö and Çetin, B and Yetim, H}, title = {Assessment of Multi Fragment Melting Analysis System (MFMAS) for the Identification of Food-Borne Yeasts.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {716-725}, pmid = {29484449}, issn = {1432-0991}, support = {TOVAG 114O177//Türkiye Bilimsel ve Teknolojik Araştirma Kurumu/ ; }, mesh = {Beverages/microbiology ; DNA, Fungal/genetics ; Food Microbiology ; Phylogeny ; Polymorphism, Restriction Fragment Length/genetics ; Saccharomyces cerevisiae/classification/genetics ; Yeasts/classification/*genetics ; }, abstract = {Multi Fragment Melting Analysis System (MFMAS) is a novel approach that was developed for the species-level identification of microorganisms. It is a software-assisted system that performs concurrent melting analysis of 8 different DNA fragments to obtain a fingerprint of each strain analyzed. The identification is performed according to the comparison of these fingerprints with the fingerprints of known yeast species recorded in a database to obtain the best possible match. In this study, applicability of the yeast version of the MFMAS (MFMAS-yeast) was evaluated for the identification of food-associated yeast species. For this purpose, in this study, a total of 145 yeast strains originated from foods and beverages and 19 standard yeast strains were tested. The DNAs isolated from these yeast strains were analyzed by the MFMAS, and their species were successfully identified with a similarity rate of 95% or higher. It was shown that the strains belonged to 43 different yeast species that are widely found in the foods. A clear discrimination was also observed in the phylogenetically related species. In conclusion, it might be suggested that the MFMAS-yeast seems to be a highly promising approach for a rapid, accurate, and one-step identification of the yeasts isolated from food products and/or their processing environments.}, } @article {pmid29483681, year = {2018}, author = {Watson, JEM and Evans, T and Venter, O and Williams, B and Tulloch, A and Stewart, C and Thompson, I and Ray, JC and Murray, K and Salazar, A and McAlpine, C and Potapov, P and Walston, J and Robinson, JG and Painter, M and Wilkie, D and Filardi, C and Laurance, WF and Houghton, RA and Maxwell, S and Grantham, H and Samper, C and Wang, S and Laestadius, L and Runting, RK and Silva-Chávez, GA and Ervin, J and Lindenmayer, D}, title = {The exceptional value of intact forest ecosystems.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {599-610}, doi = {10.1038/s41559-018-0490-x}, pmid = {29483681}, issn = {2397-334X}, abstract = {As the terrestrial human footprint continues to expand, the amount of native forest that is free from significant damaging human activities is in precipitous decline. There is emerging evidence that the remaining intact forest supports an exceptional confluence of globally significant environmental values relative to degraded forests, including imperilled biodiversity, carbon sequestration and storage, water provision, indigenous culture and the maintenance of human health. Here we argue that maintaining and, where possible, restoring the integrity of dwindling intact forests is an urgent priority for current global efforts to halt the ongoing biodiversity crisis, slow rapid climate change and achieve sustainability goals. Retaining the integrity of intact forest ecosystems should be a central component of proactive global and national environmental strategies, alongside current efforts aimed at halting deforestation and promoting reforestation.}, } @article {pmid29483680, year = {2018}, author = {Zhu, D and Ciais, P and Chang, J and Krinner, G and Peng, S and Viovy, N and Peñuelas, J and Zimov, S}, title = {The large mean body size of mammalian herbivores explains the productivity paradox during the Last Glacial Maximum.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {640-649}, pmid = {29483680}, issn = {2397-334X}, support = {610028//European Research Council/International ; }, abstract = {Large herbivores are a major agent in ecosystems, influencing vegetation structure, and carbon and nutrient flows. During the last glacial period, a mammoth steppe ecosystem prevailed in the unglaciated northern lands, supporting a high diversity and density of megafaunal herbivores. The apparent discrepancy between abundant megafauna and the expected low vegetation productivity under a generally harsher climate with a lower CO2 concentration, termed the productivity paradox, requires large-scale quantitative analysis using process-based ecosystem models. However, most of the current global dynamic vegetation models (DGVMs) lack explicit representation of large herbivores. Here we incorporated a grazing module in a DGVM based on physiological and demographic equations for wild large grazers, taking into account feedbacks of large grazers on vegetation. The model was applied globally for present-day and the Last Glacial Maximum (LGM). The present-day results of potential grazer biomass, combined with an empirical land-use map, infer a reduction in wild grazer biomass by 79-93% owing to anthropogenic land replacement of natural grasslands. For the LGM, we find that the larger mean body size of mammalian herbivores than today is the crucial clue to explain the productivity paradox, due to a more efficient exploitation of grass production by grazers with a large body size.}, } @article {pmid29483679, year = {2018}, author = {Antonelli, A and Perrigo, A}, title = {The science and ethics of extinction.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {581}, doi = {10.1038/s41559-018-0500-z}, pmid = {29483679}, issn = {2397-334X}, } @article {pmid29483678, year = {2018}, author = {Skoglund, P}, title = {Northwest passage to Scandinavia.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {593-594}, doi = {10.1038/s41559-018-0505-7}, pmid = {29483678}, issn = {2397-334X}, } @article {pmid29483657, year = {2018}, author = {Curson, ARJ and Williams, BT and Pinchbeck, BJ and Sims, LP and Martínez, AB and Rivera, PPL and Kumaresan, D and Mercadé, E and Spurgin, LG and Carrión, O and Moxon, S and Cattolico, RA and Kuzhiumparambil, U and Guagliardo, P and Clode, PL and Raina, JB and Todd, JD}, title = {DSYB catalyses the key step of dimethylsulfoniopropionate biosynthesis in many phytoplankton.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {430-439}, doi = {10.1038/s41564-018-0119-5}, pmid = {29483657}, issn = {2058-5276}, abstract = {Dimethylsulfoniopropionate (DMSP) is a globally important organosulfur molecule and the major precursor for dimethyl sulfide. These compounds are important info-chemicals, key nutrients for marine microorganisms, and are involved in global sulfur cycling, atmospheric chemistry and cloud formation1-3. DMSP production was thought to be confined to eukaryotes, but heterotrophic bacteria can also produce DMSP through the pathway used by most phytoplankton 4 , and the DsyB enzyme catalysing the key step of this pathway in bacteria was recently identified 5 . However, eukaryotic phytoplankton probably produce most of Earth's DMSP, yet no DMSP biosynthesis genes have been identified in any such organisms. Here we identify functional dsyB homologues, termed DSYB, in many phytoplankton and corals. DSYB is a methylthiohydroxybutryate methyltransferase enzyme localized in the chloroplasts and mitochondria of the haptophyte Prymnesium parvum, and stable isotope tracking experiments support these organelles as sites of DMSP synthesis. DSYB transcription levels increased with DMSP concentrations in different phytoplankton and were indicative of intracellular DMSP. Identification of the eukaryotic DSYB sequences, along with bacterial dsyB, provides the first molecular tools to predict the relative contributions of eukaryotes and prokaryotes to global DMSP production. Furthermore, evolutionary analysis suggests that eukaryotic DSYB originated in bacteria and was passed to eukaryotes early in their evolution.}, } @article {pmid29483656, year = {2018}, author = {Pardiñas, AF and Holmans, P and Pocklington, AJ and Escott-Price, V and Ripke, S and Carrera, N and Legge, SE and Bishop, S and Cameron, D and Hamshere, ML and Han, J and Hubbard, L and Lynham, A and Mantripragada, K and Rees, E and MacCabe, JH and McCarroll, SA and Baune, BT and Breen, G and Byrne, EM and Dannlowski, U and Eley, TC and Hayward, C and Martin, NG and McIntosh, AM and Plomin, R and Porteous, DJ and Wray, NR and Caballero, A and Geschwind, DH and Huckins, LM and Ruderfer, DM and Santiago, E and Sklar, P and Stahl, EA and Won, H and Agerbo, E and Als, TD and Andreassen, OA and Bækvad-Hansen, M and Mortensen, PB and Pedersen, CB and Børglum, AD and Bybjerg-Grauholm, J and Djurovic, S and Durmishi, N and Pedersen, MG and Golimbet, V and Grove, J and Hougaard, DM and Mattheisen, M and Molden, E and Mors, O and Nordentoft, M and Pejovic-Milovancevic, M and Sigurdsson, E and Silagadze, T and Hansen, CS and Stefansson, K and Stefansson, H and Steinberg, S and Tosato, S and Werge, T and , and , and Collier, DA and Rujescu, D and Kirov, G and Owen, MJ and O'Donovan, MC and Walters, JTR and , and , and , and , }, title = {Common schizophrenia alleles are enriched in mutation-intolerant genes and in regions under strong background selection.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {381-389}, pmid = {29483656}, issn = {1546-1718}, support = {R01 AA007535/AA/NIAAA NIH HHS/United States ; R01 AA014041/AA/NIAAA NIH HHS/United States ; R01 MH066206/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; R01 AA013326/AA/NIAAA NIH HHS/United States ; R01 HD059215/HD/NICHD NIH HHS/United States ; R56 DA012854/DA/NIDA NIH HHS/United States ; R01 AA013321/AA/NIAAA NIH HHS/United States ; R01 DA012854/DA/NIDA NIH HHS/United States ; R01 HD044454/HD/NICHD NIH HHS/United States ; K08 DA019951/DA/NIDA NIH HHS/United States ; K99 MH113823/MH/NIMH NIH HHS/United States ; //Wellcome Trust/United Kingdom ; R01 AA013320/AA/NIAAA NIH HHS/United States ; }, abstract = {Schizophrenia is a debilitating psychiatric condition often associated with poor quality of life and decreased life expectancy. Lack of progress in improving treatment outcomes has been attributed to limited knowledge of the underlying biology, although large-scale genomic studies have begun to provide insights. We report a new genome-wide association study of schizophrenia (11,260 cases and 24,542 controls), and through meta-analysis with existing data we identify 50 novel associated loci and 145 loci in total. Through integrating genomic fine-mapping with brain expression and chromosome conformation data, we identify candidate causal genes within 33 loci. We also show for the first time that the common variant association signal is highly enriched among genes that are under strong selective pressures. These findings provide new insights into the biology and genetic architecture of schizophrenia, highlight the importance of mutation-intolerant genes and suggest a mechanism by which common risk variants persist in the population.}, } @article {pmid29483655, year = {2018}, author = {Guallar, D and Bi, X and Pardavila, JA and Huang, X and Saenz, C and Shi, X and Zhou, H and Faiola, F and Ding, J and Haruehanroengra, P and Yang, F and Li, D and Sanchez-Priego, C and Saunders, A and Pan, F and Valdes, VJ and Kelley, K and Blanco, MG and Chen, L and Wang, H and Sheng, J and Xu, M and Fidalgo, M and Shen, X and Wang, J}, title = {RNA-dependent chromatin targeting of TET2 for endogenous retrovirus control in pluripotent stem cells.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {443-451}, pmid = {29483655}, issn = {1546-1718}, support = {R01 GM095942/GM/NIGMS NIH HHS/United States ; R01 HL112294/HL/NHLBI NIH HHS/United States ; R21 HD087722/HD/NICHD NIH HHS/United States ; }, abstract = {Ten-eleven translocation (TET) proteins play key roles in the regulation of DNA-methylation status by oxidizing 5-methylcytosine (5mC) to generate 5-hydroxymethylcytosine (5hmC), which can both serve as a stable epigenetic mark and participate in active demethylation. Unlike the other members of the TET family, TET2 does not contain a DNA-binding domain, and it remains unclear how it is recruited to chromatin. Here we show that TET2 is recruited by the RNA-binding protein Paraspeckle component 1 (PSPC1) through transcriptionally active loci, including endogenous retroviruses (ERVs) whose long terminal repeats (LTRs) have been co-opted by mammalian genomes as stage- and tissue-specific transcriptional regulatory modules. We found that PSPC1 and TET2 contribute to ERVL and ERVL-associated gene regulation by both transcriptional repression via histone deacetylases and post-transcriptional destabilization of RNAs through 5hmC modification. Our findings provide evidence for a functional role of transcriptionally active ERVs as specific docking sites for RNA epigenetic modulation and gene regulation.}, } @article {pmid29483654, year = {2018}, author = {di Iulio, J and Bartha, I and Wong, EHM and Yu, HC and Lavrenko, V and Yang, D and Jung, I and Hicks, MA and Shah, N and Kirkness, EF and Fabani, MM and Biggs, WH and Ren, B and Venter, JC and Telenti, A}, title = {The human noncoding genome defined by genetic diversity.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {333-337}, doi = {10.1038/s41588-018-0062-7}, pmid = {29483654}, issn = {1546-1718}, abstract = {Understanding the significance of genetic variants in the noncoding genome is emerging as the next challenge in human genomics. We used the power of 11,257 whole-genome sequences and 16,384 heptamers (7-nt motifs) to build a map of sequence constraint for the human species. This build differed substantially from traditional maps of interspecies conservation and identified regulatory elements among the most constrained regions of the genome. Using new Hi-C experimental data, we describe a strong pattern of coordination over 2 Mb where the most constrained regulatory elements associate with the most essential genes. Constrained regions of the noncoding genome are up to 52-fold enriched for known pathogenic variants as compared to unconstrained regions (21-fold when compared to the genome average). This map of sequence constraint across thousands of individuals is an asset to help interpret noncoding elements in the human genome, prioritize variants and reconsider gene units at a larger scale.}, } @article {pmid29483653, year = {2018}, author = {Kotlarz, D and Marquardt, B and Barøy, T and Lee, WS and Konnikova, L and Hollizeck, S and Magg, T and Lehle, AS and Walz, C and Borggraefe, I and Hauck, F and Bufler, P and Conca, R and Wall, SM and Schumacher, EM and Misceo, D and Frengen, E and Bentsen, BS and Uhlig, HH and Hopfner, KP and Muise, AM and Snapper, SB and Strømme, P and Klein, C}, title = {Human TGF-β1 deficiency causes severe inflammatory bowel disease and encephalopathy.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {344-348}, doi = {10.1038/s41588-018-0063-6}, pmid = {29483653}, issn = {1546-1718}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; }, abstract = {Transforming growth factor (TGF)-β1 (encoded by TGFB1) is the prototypic member of the TGF-β family of 33 proteins that orchestrate embryogenesis, development and tissue homeostasis1,2. Following its discovery 3 , enormous interest and numerous controversies have emerged about the role of TGF-β in coordinating the balance of pro- and anti-oncogenic properties4,5, pro- and anti-inflammatory effects 6 , or pro- and anti-fibrinogenic characteristics 7 . Here we describe three individuals from two pedigrees with biallelic loss-of-function mutations in the TGFB1 gene who presented with severe infantile inflammatory bowel disease (IBD) and central nervous system (CNS) disease associated with epilepsy, brain atrophy and posterior leukoencephalopathy. The proteins encoded by the mutated TGFB1 alleles were characterized by impaired secretion, function or stability of the TGF-β1-LAP complex, which is suggestive of perturbed bioavailability of TGF-β1. Our study shows that TGF-β1 has a critical and nonredundant role in the development and homeostasis of intestinal immunity and the CNS in humans.}, } @article {pmid29483357, year = {2018}, author = {Hasselmo, ME and Stern, CE}, title = {A network model of behavioural performance in a rule learning task.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483357}, issn = {1471-2970}, support = {R01 MH060013/MH/NIMH NIH HHS/United States ; R01 MH061492/MH/NIMH NIH HHS/United States ; }, mesh = {Acetylcholine/metabolism ; Action Potentials/physiology ; Adult ; Attention/physiology ; Cognition/physiology ; Cues ; Humans ; *Individuality ; Learning/*physiology ; *Models, Neurological ; Neocortex/*physiology ; Nerve Net/*physiology ; Neurons/cytology/*physiology ; Receptors, Muscarinic/metabolism ; Synaptic Transmission/physiology ; }, abstract = {Humans demonstrate differences in performance on cognitive rule learning tasks which could involve differences in properties of neural circuits. An example model is presented to show how gating of the spread of neural activity could underlie rule learning and the generalization of rules to previously unseen stimuli. This model uses the activity of gating units to regulate the pattern of connectivity between neurons responding to sensory input and subsequent gating units or output units. This model allows analysis of network parameters that could contribute to differences in cognitive rule learning. These network parameters include differences in the parameters of synaptic modification and presynaptic inhibition of synaptic transmission that could be regulated by neuromodulatory influences on neural circuits. Neuromodulatory receptors play an important role in cognitive function, as demonstrated by the fact that drugs that block cholinergic muscarinic receptors can cause cognitive impairments. In discussions of the links between neuromodulatory systems and biologically based traits, the issue of mechanisms through which these linkages are realized is often missing. This model demonstrates potential roles of neural circuit parameters regulated by acetylcholine in learning context-dependent rules, and demonstrates the potential contribution of variation in neural circuit properties and neuromodulatory function to individual differences in cognitive function.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483356, year = {2018}, author = {Posner, MI and Rothbart, MK}, title = {Temperament and brain networks of attention.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483356}, issn = {1471-2970}, mesh = {Adult ; Attention/*physiology ; Brain/anatomy & histology/physiology ; Child ; Child Development ; Child, Preschool ; Cues ; Executive Function/*physiology ; Female ; Humans ; *Individuality ; Infant ; Longitudinal Studies ; Male ; Nerve Net/anatomy & histology/physiology ; Neuropsychological Tests ; Orientation/*physiology ; Psychomotor Performance/physiology ; Surveys and Questionnaires ; Temperament/*physiology ; }, abstract = {The attention networks of the human brain are important control systems that develop from infancy into adulthood. While they are common to everyone, they differ in efficiency, forming the basis of individual differences in attention. We have developed methods for measuring the efficiency of these networks in older children and adults and have also examined their development from infancy. During infancy the alerting and orienting networks are dominant in control of the infant's actions, but later an executive network dominates. Each network has been associated with its main neuromodulator and these have led to associations with genes related to that network neuromodulator. The links between parent reports of their child's effortful control and the executive attention network allow us to associate molecular mechanisms to fundamental behavioural outcomes.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483355, year = {2018}, author = {Uher, J and Trofimova, I and Sulis, W and Netter, P and Pessoa, L and Posner, MI and Rothbart, MK and Rusalov, V and Peterson, IT and Schmidt, LA}, title = {Diversity in action: exchange of perspectives and reflections on taxonomies of individual differences.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483355}, issn = {1471-2970}, mesh = {Brain/anatomy & histology/physiology ; Emotions/*physiology ; History, 20th Century ; History, 21st Century ; History, Medieval ; Humans ; *Individuality ; Interdisciplinary Research ; Mental Disorders/physiopathology/*psychology ; *Models, Psychological ; Nerve Net/anatomy & histology/physiology ; Psychomotor Performance/physiology ; Psychophysiology/*classification/history ; Temperament/*physiology ; Terminology as Topic ; }, abstract = {Throughout the last 2500 years, the classification of individual differences in healthy people and their extreme expressions in mental disorders has remained one of the most difficult challenges in science that affects our ability to explore individuals' functioning, underlying psychobiological processes and pathways of development. To facilitate analyses of the principles required for studying individual differences, this theme issue brought together prominent scholars from diverse backgrounds of which many bring unique combinations of cross-disciplinary experiences and perspectives that help establish connections and promote exchange across disciplines. This final paper presents brief commentaries of some of our authors and further scholars exchanging perspectives and reflecting on the contributions of this theme issue.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483354, year = {2018}, author = {Uher, J}, title = {Taxonomic models of individual differences: a guide to transdisciplinary approaches.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483354}, issn = {1471-2970}, mesh = {Brain/physiology ; Emotions/*physiology ; Humans ; *Individuality ; Interdisciplinary Research/methods ; Language ; *Models, Psychological ; Multifactor Dimensionality Reduction/statistics & numerical data ; Psychomotor Performance/physiology ; Psychophysiology/*methods ; Temperament/*physiology ; Terminology as Topic ; }, abstract = {Models and constructs of individual differences are numerous and diverse. But detecting commonalities, differences and interrelations is hindered by the common abstract terms (e.g. 'personality', 'temperament', 'traits') that do not reveal the particular phenomena denoted. This article applies a transdisciplinary paradigm for research on individuals that builds on complexity theory and epistemological complementarity. Its philosophical, metatheoretical and methodological frameworks provide concepts to differentiate various kinds of phenomena (e.g. physiology, behaviour, psyche, language). They are used to scrutinize the field's basic concepts and to elaborate methodological foundations for taxonomizing individual variations in humans and other species. This guide to developing comprehensive and representative models explores the decisions taxonomists must make about which individual variations to include, which to retain and how to model them. Selection and reduction approaches from various disciplines are classified by their underlying rationales, pinpointing possibilities and limitations. Analyses highlight that individuals' complexity cannot be captured by one universal model. Instead, multiple models phenotypically taxonomizing different kinds of variability in different kinds of phenomena are needed to explore their causal and functional interrelations and ontogenetic development that are then modelled in integrative and explanatory taxonomies. This research agenda requires the expertise of many disciplines and is inherently transdisciplinary.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483353, year = {2018}, author = {Saucier, G}, title = {Culture, morality and individual differences: comparability and incomparability across species.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483353}, issn = {1471-2970}, mesh = {Animals ; Biological Evolution ; Bullying/prevention & control ; *Culture ; Deception ; Humans ; *Individuality ; Language ; *Morals ; Pan troglodytes/physiology/psychology ; Punishment ; Religion ; *Social Norms ; Species Specificity ; }, abstract = {Major routes to identifying individual differences (in diverse species) include studies of behaviour patterns as represented in language and neurophysiology. But results from these approaches appear not to converge on some major dimensions. Identifying dimensions of human variation least applicable to non-human species may help to partition human-specific individual differences of recent evolutionary origin from those shared across species. Human culture includes learned, enforced social-norm systems that are symbolically reinforced and referenced in displays signalling adherence. At a key juncture in human evolution bullying aggression and deception-based cheating apparently became censured in the language of a moral community, enabling mutual observation coordinated in gossip, associated with external sanctions. That still-conserved cultural paradigm moralistically regulates selfish advantage-taking, with shared semantics and explicit rules. Ethics and moral codes remain critical and universal components of human culture and have a stronger imprint in language than most aspects of the currently popular Big-Five taxonomy, a model that sets out five major lines of individual-differences variation in human personality. In other species (e.g. chimpanzees), human observers might see apparent individual differences in morality-relevant traits, but not because the animals have human-analogue sanctioning systems. Removing the moral dimension of personality and other human-specific manifestations (e.g. religion) may aid in identifying those other bases of individual differences more ubiquitous across species.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483352, year = {2018}, author = {Sulis, W}, title = {Assessing the continuum between temperament and affective illness: psychiatric and mathematical perspectives.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483352}, issn = {1471-2970}, mesh = {Affective Disorders, Psychotic/physiopathology/*psychology ; Humans ; *Individuality ; Models, Psychological ; *Models, Statistical ; Neurobiology/*methods/statistics & numerical data ; Nonlinear Dynamics ; Psychiatry/*methods/statistics & numerical data ; Systems Theory ; Temperament/*physiology ; Terminology as Topic ; Time Factors ; }, abstract = {Temperament of healthy people and mental illnesses, particularly affective disorders, have been conjectured to lie along a continuum of neurobehavioural regulation. Understanding the nature of this continuum may better inform the construction of taxonomies for both categories of behaviour. Both temperament and mental illness refer to patterns of behaviour that manifest over long time scales (weeks to years) and they appear to share many underlying neuroregulatory systems. This continuum is discussed from the perspectives of nonlinear dynamical systems theory, neurobiology and psychiatry as applied to understanding such multiscale time-series behaviour. Particular emphasis is given to issues of generativity, fungibility, metastability, non-stationarity and contextuality. Implications of these dynamical properties for the development of taxonomies will be discussed. Problems with the over-reliance of psychologists on statistical and mathematical methods in deriving their taxonomies (particularly those based on factor analysis) will be discussed from a dynamical perspective. An alternative approach to temperament based upon functionality, and its discriminative capabilities in mental illness, is presented.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483351, year = {2018}, author = {Trofimova, I}, title = {Functionality versus dimensionality in psychological taxonomies, and a puzzle of emotional valence.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483351}, issn = {1471-2970}, mesh = {Brain/anatomy & histology/physiology ; Emotions/*physiology ; Humans ; *Individuality ; Mental Disorders/classification/physiopathology/*psychology ; *Models, Psychological ; Nerve Net/anatomy & histology/physiology ; Neuronal Plasticity/physiology ; Orientation/physiology ; Psychomotor Performance/physiology ; Psychophysiology/*methods ; Temperament/*physiology ; Terminology as Topic ; }, abstract = {This paper applies evolutionary and functional constructivism approaches to the discussion of psychological taxonomies, as implemented in the neurochemical model Functional Ensemble of Temperament (FET). FET asserts that neurochemical systems developed in evolution to regulate functional-dynamical aspects of construction of actions: orientation, selection (integration), energetic maintenance, and management of automatic behavioural elements. As an example, the paper reviews the neurochemical mechanisms of interlocking between emotional dispositions and performance capacities. Research shows that there are no specific neurophysiological systems of positive or negative affect, and that emotional valence is rather an integrative product of many brain systems during estimations of needs and the capacities required to satisfy these needs. The interlocking between emotional valence and functional aspects of performance appears to be only partial since all monoamine and opioid receptor systems play important roles in non-emotional aspects of behaviour, in addition to emotionality. This suggests that the Positive/Negative Affect framework for DSM/ICD classifications of mental disorders oversimplifies the structure of non-emotionality symptoms of these disorders. Contingent dynamical relationships between neurochemical systems cannot be represented by linear statistical models searching for independent dimensions (such as factor analysis); nevertheless, these relationships should be reflected in psychological and psychiatric taxonomies.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483350, year = {2018}, author = {Rusalov, V}, title = {Functional systems theory and the activity-specific approach in psychological taxonomies.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483350}, issn = {1471-2970}, mesh = {Emotions/*physiology ; History, 20th Century ; History, 21st Century ; Humans ; *Individuality ; *Models, Psychological ; Neuronal Plasticity/physiology ; Psychomotor Performance/physiology ; Psychophysiology/*classification/history ; Russia ; *Systems Theory ; Temperament/*physiology ; Terminology as Topic ; }, abstract = {This brief opinion contribution reflects on the application of Anokhin's functional systems theory in the development of models of temperament in Russian differential psychophysiology. It points to the benefits of using an activity-specific approach in temperament theory. This approach suggests separating traits related to physical, communicative and mental aspects of behaviour.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483349, year = {2018}, author = {Netter, P}, title = {Benefits and limitations of drug studies in temperament research: biochemical responses as indicators of temperament.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483349}, issn = {1471-2970}, mesh = {Brain/drug effects/metabolism/physiopathology ; Cluster Analysis ; Dopamine/metabolism ; Dose-Response Relationship, Drug ; Exploratory Behavior/drug effects ; Female ; Humans ; Impulsive Behavior/drug effects ; Individuality ; Male ; Neuroticism/*drug effects ; Neurotransmitter Uptake Inhibitors/*pharmacology ; Norepinephrine/metabolism ; Personality Disorders/diagnosis/*drug therapy/physiopathology/psychology ; Psychotropic Drugs/*pharmacology ; Serotonin/metabolism ; Temperament/*drug effects/physiology ; }, abstract = {This paper presents a discussion of principles and problems of neurotransmitter challenge tests using examples of experiments, most of which were performed in the author's laboratory. Drugs targeting synthesis, release, receptors or reuptake of dopamine, serotonin and noradrenergic transmitter (TM) systems were used for characterizing or discriminating certain temperament or personality traits and their sub-factors. Any personality or temperament trait is characterized by multiple TM responses, thus constellations of hormone responses to drugs acting on different TM systems or on different sources of TM activity were investigated within individuals in crossover designs. The major conclusions are: (i) intra-individual patterns of hormone responses to different TM-related drugs, or to agonists and antagonists, can help to discriminate subtypes of temperament dimensions, and (ii) the latency and shape of response curves may help specify processes of biological responses related to psychological dimensions and reveal common TM sensitivities in clusters of traits. TM sensitivity, defined by hormone responses, does not always correspond to accompanying behavioural indicators, but may provide more specific information on underlying mechanisms. Additional consideration of drug doses and experimental induction of stressors may serve to identify temperament-related susceptibilities to certain drugs. Limitations of the challenge approach and recommendations for future research are discussed.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483348, year = {2018}, author = {Cloninger, CR and Zwir, I}, title = {What is the natural measurement unit of temperament: single traits or profiles?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483348}, issn = {1471-2970}, support = {R01 MH060879/MH/NIMH NIH HHS/United States ; }, mesh = {Cluster Analysis ; Epistasis, Genetic ; Gene-Environment Interaction ; *Genetic Pleiotropy ; Genome-Wide Association Study ; Genotype ; Humans ; Individuality ; Phenotype ; *Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; Schizophrenia/diagnosis/*genetics/physiopathology ; Schizotypal Personality Disorder/diagnosis/*genetics/physiopathology ; *Temperament ; Unsupervised Machine Learning ; }, abstract = {There is fundamental doubt about whether the natural unit of measurement for temperament and personality corresponds to single traits or to multi-trait profiles that describe the functioning of a whole person. Biogenetic researchers of temperament usually assume they need to focus on individual traits that differ between individuals. Recent research indicates that a shift of emphasis to understand processes within the individual is crucial for identifying the natural building blocks of temperament. Evolution and development operate on adaptation of whole organisms or persons, not on individual traits or categories. Adaptive functioning generally depends on feedback among many variable processes in ways that are characteristic of complex adaptive systems, not machines with separate parts. Advanced methods of unsupervised machine learning can now be applied to genome-wide association studies and brain imaging in order to uncover the genotypic-phenotypic architecture of traits like temperament, which are strongly influenced by complex interactions, such as genetic epistasis, pleiotropy and gene-environment interactions. We have found that the heritability of temperament can be nearly fully explained by a large number of genetic variants that are unique for multi-trait profiles, not single traits. The implications of this finding for research design and precision medicine are discussed.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483347, year = {2018}, author = {Sallis, H and Davey Smith, G and Munafò, MR}, title = {Genetics of biologically based psychological differences.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483347}, issn = {1471-2970}, support = {MC_UU_12013/1//Medical Research Council/United Kingdom ; MC_UU_12013/6//Medical Research Council/United Kingdom ; }, mesh = {*Genetic Heterogeneity ; Genetics, Population ; Genome, Human ; Genome-Wide Association Study ; Genotype ; Humans ; Individuality ; *Inheritance Patterns ; Mendelian Randomization Analysis ; *Neuroticism ; Personality Disorders/diagnosis/*genetics/physiopathology/psychology ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait, Heritable ; }, abstract = {In recent years, substantial effort has gone into disentangling the genetic contribution to individual differences in behaviour (such as personality and temperament traits). Heritability estimates from twin and family studies, and more recently using whole genome approaches, suggest a substantial genetic component to these traits. However, efforts to identify the genes that influence these traits have had relatively little success. Here, we review current work investigating the heritability of individual differences in behavioural traits and provide an overview of the results from genome-wide association analyses of these traits to date. In addition, we discuss the implications of these findings for the potential applications of Mendelian randomization.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483346, year = {2018}, author = {Acevedo, B and Aron, E and Pospos, S and Jessen, D}, title = {The functional highly sensitive brain: a review of the brain circuits underlying sensory processing sensitivity and seemingly related disorders.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483346}, issn = {1471-2970}, mesh = {Adaptation, Psychological ; Autism Spectrum Disorder/diagnosis/*physiopathology/psychology ; Awareness/physiology ; Biomarkers/analysis ; Empathy/physiology ; Homeostasis/physiology ; Humans ; Nerve Net/*physiopathology ; Reaction Time ; Schizophrenia/diagnosis/*physiopathology ; Sensorimotor Cortex/*physiopathology ; Somatosensory Disorders/diagnosis/*physiopathology/psychology ; Stress Disorders, Post-Traumatic/diagnosis/*physiopathology/psychology ; }, abstract = {During the past decade, research on the biological basis of sensory processing sensitivity (SPS)-a genetically based trait associated with greater sensitivity and responsivity to environmental and social stimuli-has burgeoned. As researchers try to characterize this trait, it is still unclear how SPS is distinct from seemingly related clinical disorders that have overlapping symptoms, such as sensitivity to the environment and hyper-responsiveness to incoming stimuli. Thus, in this review, we compare the neural regions implicated in SPS with those found in fMRI studies of-Autism Spectrum Disorder (ASD), Schizophrenia (SZ) and Post-Traumatic Stress Disorder (PTSD) to elucidate the neural markers and cardinal features of SPS versus these seemingly related clinical disorders. We propose that SPS is a stable trait that is characterized by greater empathy, awareness, responsivity and depth of processing to salient stimuli. We conclude that SPS is distinct from ASD, SZ and PTSD in that in response to social and emotional stimuli, SPS differentially engages brain regions involved in reward processing, memory, physiological homeostasis, self-other processing, empathy and awareness. We suggest that this serves species survival via deep integration and memory for environmental and social information that may subserve well-being and cooperation.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483345, year = {2018}, author = {Hoyniak, CP and Petersen, IT and Bates, JE and Molfese, DL}, title = {The neural correlates of temperamental inhibitory control in toddlers.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483345}, issn = {1471-2970}, support = {F31 MH100814/MH/NIMH NIH HHS/United States ; }, mesh = {Brain Mapping ; Child, Preschool ; Electroencephalography ; Evoked Potentials/*physiology ; Female ; Gyrus Cinguli/anatomy & histology/*physiology ; Humans ; *Inhibition (Psychology) ; Male ; Nerve Net/anatomy & histology/*physiology ; Neuropsychological Tests ; Prefrontal Cortex/anatomy & histology/*physiology ; Reaction Time ; Temperament/*physiology ; }, abstract = {The current study examined the association between effortful control and a well-studied neural index of self-regulation, the N2 event-related potential (ERP) component, in toddlers. Participants included 107 toddlers (44 girls) assessed at 30, 36 and 42 months of age. Participants completed a Go/NoGo task while electroencephalography data were recorded. The study focused on the N2 ERP component. Parent-reported effortful control was examined in association with the NoGo N2 ERP component. Findings suggest a positive association between the NoGo N2 component and the inhibitory control subscale of the wider effortful control dimension, suggesting that the N2 component may index processes associated with temperamental effortful control.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483344, year = {2018}, author = {Jones, NA and Sloan, A}, title = {Neurohormones and temperament interact during infant development.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483344}, issn = {1471-2970}, mesh = {Child ; Child Development ; Female ; Fetus ; Humans ; Hydrocortisone/*metabolism ; Individuality ; Infant ; Infant Behavior/physiology/*psychology ; Longitudinal Studies ; Male ; Maternal Exposure/adverse effects ; Models, Psychological ; Neurotransmitter Agents/*metabolism ; Oxytocin/*metabolism ; Pregnancy ; Prenatal Exposure Delayed Effects/etiology/physiopathology/psychology ; Stress, Psychological/metabolism/*physiopathology ; Temperament/*physiology ; }, abstract = {The infant's psycho-physiological regulatory system begins to develop prenatally and continues to mature during the postnatal period. Temperament is a construct comprising tonic individual differences in dispositional physiological and behavioural reactions as well as an evolving ability to regulate to environmental conditions. Theoretical models and research have shown that neurohormonal and -physiological factors contribute to individual development and impact infant behaviours as well as the developing regulatory system. Moreover, prenatal maternal risks such as stress and depression are thought to programme fetal regulatory tendencies and that influences neural and behavioural functioning in infancy. The purpose of this review is to examine the theories and research that link infant temperament to neurohormonal and -physiological development in typically developing infants and in those exposed to environmental risk. Research has demonstrated associations between individual variation in physiological stress responses and regulation (measured with cortisol). Moreover, studies have noted an association with physiological regulation and socio-emotional interaction (as measured by the touch-oxytocin link) that may buffer emotional dysregulation. The interaction between individual differences in temperamental tendencies, neurohormonal and -physiological patterns will be discussed by presenting data from studies that have shown that infant neurohormonal and -physiological functioning sets an important trajectory for the development of the individual.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483343, year = {2018}, author = {Kagan, J}, title = {Perspectives on two temperamental biases.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483343}, issn = {1471-2970}, mesh = {Adolescent ; Amygdala/anatomy & histology/physiology ; Child ; Child, Preschool ; Emotions/*physiology ; Female ; Humans ; Infant ; Infant Behavior/*psychology ; Longitudinal Studies ; Male ; Motivation/physiology ; Personality/*physiology ; Personality Assessment ; Personality Disorders/physiopathology/*psychology ; *Reactive Inhibition ; Temperament/*physiology ; }, abstract = {This paper describes the contribution of two infant temperamental biases to variation in behaviour and biology over the first 18 years in a sample of middle-class Caucasian children. One bias, called high reactive, is defined by frequent display of limb activity and crying in four-month-old infants to unexpected or unfamiliar events. The other, called low reactive, is defined by the opposite pair of behaviours to the same incentives. High reactive infants are likely to display cautious, avoidant responses and signs of an excitable amygdala to unexpected experiences. Low reactives are characterized by a sociable, emotionally spontaneous profile to the same experiences and a minimally excitable amygdala. However, each bias is a better predictor of the future traits that are unlikely to develop than the ones that do. The final pattern of traits is a function of the person's temperaments, life history, and current circumstances.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483342, year = {2018}, author = {Farde, L and Plavén-Sigray, P and Borg, J and Cervenka, S}, title = {Brain neuroreceptor density and personality traits: towards dimensional biomarkers for psychiatric disorders.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483342}, issn = {1471-2970}, mesh = {Adult ; Biomarkers/metabolism ; Brain/diagnostic imaging/metabolism/physiopathology ; Brain Mapping ; Case-Control Studies ; Depression/diagnostic imaging/metabolism/*physiopathology ; Dopamine/*metabolism ; Female ; Humans ; Individuality ; Male ; Neurotransmitter Agents/metabolism ; Personality Disorders/diagnostic imaging/metabolism/*physiopathology ; Positron-Emission Tomography ; Schizophrenia/diagnostic imaging/metabolism/*physiopathology ; Sensory Receptor Cells/*metabolism ; Serotonin/*metabolism ; }, abstract = {Positron emission tomography has, for 30 years, been used in numerous case-control studies searching for hypothesized differences in the density of neuroreceptor or transporter proteins in psychiatric disorders such as schizophrenia and depression. In most cases, the results have not been conclusive. One reason could be the sizeable interindividual variability in biochemical markers, which in twin studies have shown to emanate from both environmental and genetic factors, leading to low statistical power for the detection of group effects. On the other hand, the same interindividual variability has served as an opportunity for correlative studies on the biological underpinning of behaviour. Using this approach, a series of studies has linked markers for the dopamine and serotonin system to personality traits associated with psychiatric conditions. Based on increasing evidence for the view that many psychopathological states represent extremes of a continuum rather than distinct categories, this research strategy may lead to new biological insights about the vulnerability to and pathophysiology of major psychiatric disorders.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483341, year = {2018}, author = {Blair, RJR}, title = {Traits of empathy and anger: implications for psychopathy and other disorders associated with aggression.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483341}, issn = {1471-2970}, support = {K22 MH109558/MH/NIMH NIH HHS/United States ; }, mesh = {Adult ; Aggression/*psychology ; Anger/*physiology ; Antisocial Personality Disorder/*physiopathology/psychology ; Cognition/physiology ; Empathy/*physiology ; Female ; Humans ; Irritable Mood/physiology ; Male ; }, abstract = {Empathy and anger are two social emotions that modulate an individual's risk for aggression. Empathy is an emotional reaction to another individual's emotional state. Anger is an emotional reaction to threat, frustration or social provocation. Reduced empathy, seen in psychopathy, increases the risk for goal-directed aggression. Atypically increased anger (i.e. irritability), seen in conditions like disruptive mood dysregulation disorder and borderline personality disorder, increases the risk for reactive aggression. In this paper, I will outline core neurocognitive functions that correspond to empathy and which are compromised in individuals with psychopathic traits. In addition, I will outline neurocognitive functions involved in either the generation or regulation of anger and which are compromised in psychiatric conditions at increased risk for irritability/reactive aggression. It can be hoped that improved understanding of empathy and anger will lead to better assessment tools and improved interventions to reduce aggression risk.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483340, year = {2018}, author = {Dellu-Hagedorn, F and Rivalan, M and Fitoussi, A and De Deurwaerdère, P}, title = {Inter-individual differences in the impulsive/compulsive dimension: deciphering related dopaminergic and serotonergic metabolisms at rest.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483340}, issn = {1471-2970}, mesh = {Adaptation, Psychological/*physiology ; Amygdala/metabolism ; Animals ; Anticipation, Psychological/physiology ; Behavior, Animal/*physiology ; Brain Mapping ; Delay Discounting/physiology ; Dopamine/*metabolism ; Gyrus Cinguli/metabolism ; Impulsive Behavior/*physiology ; *Individuality ; Prefrontal Cortex/metabolism ; Rats ; Rest/physiology ; Risk-Taking ; Serotonin/*metabolism ; }, abstract = {Several impulse control disorders such as ADHD, mania, personality disorders or substance abuse share common behavioural traits, like impulsiveness, risk-taking or inflexible behaviour. These disorders are treated with drugs targeting dopamine (DA) and/or serotonin (5-HT). However, the patient's monoamine imbalance that these neurotransmitters compensate is unclear. This study aims to investigate the patterns of DA and 5-HT metabolisms at rest within selected brain regions related to inter-individual variability in six main components of impulsivity/compulsivity (anticipatory hyperactivity, premature responses, delay discounting, risk-taking, perseveration, flexibility). Rats with adaptive and highly inadaptive behaviours were identified in each task and a sensitive biochemical approach allowed mapping of post-mortem endogenous monoamine tissue content in 20 brain areas. Distinct patterns of 5-HT and DA metabolisms were revealed according to the behavioural traits. Except for hyperactive responses, lower control of actions was mainly associated with a lower DA or 5-HT metabolism in prefrontal and/or subcortical areas (i.e. in orbitofrontal cortex (DA), amygdala and anterior cingulate cortex (5-HT) for inflexible and risk-prone rats). Our results reveal the complex nature of behavioural traits related to impulse control disorders through their associated monoaminergic networks at rest, paving the way for understanding the link between mental disorders and drug therapeutic actions.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483339, year = {2018}, author = {Robbins, TW}, title = {Opinion on monoaminergic contributions to traits and temperament.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483339}, issn = {1471-2970}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Acetylcholine/*physiology ; Animals ; Dopamine/*physiology ; Humans ; *Individuality ; Models, Psychological ; Nerve Net/diagnostic imaging/*physiology/physiopathology ; Neuroimaging ; Neurotransmitter Agents/physiology ; Orexins/physiology ; Psychopharmacology/methods ; Psychophysiology/methods ; Serotonin/*physiology ; Temperament/*physiology ; }, abstract = {This article critically reviews evidence relating temperamental traits and personality factors to the monoamine neurotransmitters, especially dopamine and serotonin. The genetic evidence is not yet considered to be conclusive and it is argued that basic neuroscience research on the neural basis of behaviour in experimental animals should be taken more into account. While questionnaire and lexical methodology including the 'Five Factor' theory has been informative (mostly for the traits relevant to social functioning, i.e. personality), biologically oriented approaches should be employed with more objective, theoretically grounded measures of cognition and behaviour, combined with neuroimaging and psychopharmacology, where appropriate. This strategy will enable specific functions of monoamines and other neuromodulators such as acetylcholine and neuropeptides (such as orexin) to be defined with respect to their roles in modulating activity in specific neural networks-leading to a more realistic definition of their interactive roles in complex, biologically based traits (i.e. temperament).This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483338, year = {2018}, author = {Trofimova, I and Robbins, TW and Sulis, WH and Uher, J}, title = {Taxonomies of psychological individual differences: biological perspectives on millennia-long challenges.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1744}, pages = {}, pmid = {29483338}, issn = {1471-2970}, support = {104631/Z/14/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Biofeedback, Psychology/physiology ; Factor Analysis, Statistical ; Humans ; *Individuality ; *Models, Psychological ; Psychiatry/methods ; Psychometrics/*methods ; Psychophysiology/methods ; Temperament/*physiology ; }, abstract = {This Editorial highlights a unique focus of this theme issue on the biological perspectives in deriving psychological taxonomies coming from neurochemistry, neuroanatomy, neurophysiology, genetics, psychiatry, developmental and comparative psychology-as contrasted to more common discussions of socio-cultural concepts (personality) and methods (lexical approach). It points out the importance of the distinction between temperament and personality for studies in human and animal differential psychophysiology, psychiatry and psycho-pharmacology, sport and animal practices during the past century. It also highlights the inability of common statistical methods to handle nonlinear, feedback, contingent, dynamical and multi-level relationships between psychophysiological systems of consistent psychological traits discussed in this theme issue.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'.}, } @article {pmid29483276, year = {2018}, author = {Goetz, G and Ling, T and Gupta, T and Kang, S and Wang, J and Gregory, PD and Park, BH and Palanker, D}, title = {Interferometric mapping of material properties using thermal perturbation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2499-E2508}, pmid = {29483276}, issn = {1091-6490}, support = {P30 EY026877/EY/NEI NIH HHS/United States ; U01 EY025501/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Interferometry/*methods ; Lasers ; Rats ; Rats, Long-Evans ; Retina/*chemistry/diagnostic imaging ; Retinal Pigment Epithelium/chemistry/diagnostic imaging ; Signal-To-Noise Ratio ; Tomography, Optical Coherence/*methods ; }, abstract = {Optical phase changes induced by transient perturbations provide a sensitive measure of material properties. We demonstrate the high sensitivity and speed of such methods, using two interferometric techniques: quantitative phase imaging (QPI) in transmission and phase-resolved optical coherence tomography (OCT) in reflection. Shot-noise-limited QPI can resolve energy deposition of about 3.4 mJ/cm2 in a single pulse, which corresponds to 0.8 °C temperature rise in a single cell. OCT can detect deposition of 24 mJ/cm2 energy between two scattering interfaces producing signals with about 30-dB signal-to-noise ratio (SNR), and 4.7 mJ/cm2 when SNR is 45 dB. Both techniques can image thermal changes within the thermal confinement time, which enables accurate single-shot mapping of absorption coefficients even in highly scattering samples, as well as electrical conductivity and many other material properties in biological samples at cellular scale. Integration of the phase changes along the beam path helps increase sensitivity, and the signal relaxation time reveals the size of hidden objects. These methods may enable multiple applications, ranging from temperature-controlled retinal laser therapy or gene expression to mapping electric current density and characterization of semiconductor devices with rapid pump-probe measurements.}, } @article {pmid29483275, year = {2018}, author = {Tang, W and Guo, Z and Cao, Z and Wang, M and Li, P and Meng, X and Zhao, X and Xie, Z and Wang, W and Zhou, A and Lou, C and Chen, Y}, title = {d-Sedoheptulose-7-phosphate is a common precursor for the heptoses of septacidin and hygromycin B.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2818-2823}, pmid = {29483275}, issn = {1091-6490}, mesh = {Biosynthetic Pathways ; Escherichia coli/enzymology/genetics/*metabolism ; Escherichia coli Proteins/genetics/metabolism ; Heptoses/metabolism ; Hygromycin B/*biosynthesis/chemistry ; Purine Nucleosides/biosynthesis/chemistry ; Sugar Phosphates/chemistry/*metabolism ; }, abstract = {Seven-carbon-chain-containing sugars exist in several groups of important bacterial natural products. Septacidin represents a group of l-heptopyranoses containing nucleoside antibiotics with antitumor, antifungal, and pain-relief activities. Hygromycin B, an aminoglycoside anthelmintic agent used in swine and poultry farming, represents a group of d-heptopyranoses-containing antibiotics. To date, very little is known about the biosynthesis of these compounds. Here we sequenced the genome of the septacidin producer and identified the septacidin gene cluster by heterologous expression. After determining the boundaries of the septacidin gene cluster, we studied septacidin biosynthesis by in vivo and in vitro experiments and discovered that SepB, SepL, and SepC can convert d-sedoheptulose-7-phosphate (S-7-P) to ADP-l-glycero-β-d-manno-heptose, exemplifying the involvement of ADP-sugar in microbial natural product biosynthesis. Interestingly, septacidin, a secondary metabolite from a gram-positive bacterium, shares the same ADP-heptose biosynthesis pathway with the gram-negative bacterium LPS. In addition, two acyltransferase-encoding genes sepD and sepH, were proposed to be involved in septacidin side-chain formation according to the intermediates accumulated in their mutants. In hygromycin B biosynthesis, an isomerase HygP can recognize S-7-P and convert it to ADP-d-glycero-β-d-altro-heptose together with GmhA and HldE, two enzymes from the Escherichia coli LPS heptose biosynthetic pathway, suggesting that the d-heptopyranose moiety of hygromycin B is also derived from S-7-P. Unlike the other S-7-P isomerases, HygP catalyzes consecutive isomerizations and controls the stereochemistry of both C2 and C3 positions.}, } @article {pmid29483274, year = {2018}, author = {Gottesman, ME and Mustaev, A}, title = {Inorganic phosphate, arsenate, and vanadate enhance exonuclease transcript cleavage by RNA polymerase by 2000-fold.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2746-2751}, pmid = {29483274}, issn = {1091-6490}, support = {R01 GM037219/GM/NIGMS NIH HHS/United States ; }, mesh = {Arsenates/*chemistry ; Biocatalysis ; DNA-Directed RNA Polymerases/*chemistry/metabolism ; Exonucleases/*chemistry/metabolism ; Hydrolysis ; Kinetics ; Phosphates/*chemistry ; RNA/*chemistry/genetics/metabolism ; Transcription, Genetic ; Transcriptional Elongation Factors/chemistry/genetics/metabolism ; Vanadates/*chemistry ; }, abstract = {Inorganic Pi is involved in all major biochemical pathways. Here we describe a previously unreported activity of Pi We show that Pi and its structural mimics, vanadate and arsenate, enhance nascent transcript cleavage by RNA polymerase (RNAP). They engage an Mg2+ ion in catalysis and activate an attacking water molecule. Pi, vanadate, and arsenate stimulate the intrinsic exonuclease activity of the enzyme nearly 2,000-fold at saturating concentrations of the reactant anions and Mg2+ This enhancement is comparable to that of specialized transcript cleavage protein factors Gre and TFIIS (3,000- to 4,000-fold). Unlike these protein factors, Pi and its analogs do not stimulate endonuclease transcript cleavage. Conversely, the protein factors only marginally enhance exonucleolytic cleavage. Pi thus complements cellular protein factors in assisting hydrolytic RNA cleavage by extending the repertoire of RNAP transcript degradation modes.}, } @article {pmid29483273, year = {2018}, author = {Kramer, GR and Andersen, DE and Buehler, DA and Wood, PB and Peterson, SM and Lehman, JA and Aldinger, KR and Bulluck, LP and Harding, S and Jones, JA and Loegering, JP and Smalling, C and Vallender, R and Streby, HM}, title = {Population trends in Vermivora warblers are linked to strong migratory connectivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3192-E3200}, pmid = {29483273}, issn = {1091-6490}, mesh = {*Animal Distribution ; *Animal Migration ; Animals ; *Breeding ; Ecosystem ; Male ; *Population Dynamics ; Seasons ; Songbirds/*physiology ; }, abstract = {Migratory species can experience limiting factors at different locations and during different periods of their annual cycle. In migratory birds, these factors may even occur in different hemispheres. Therefore, identifying the distribution of populations throughout their annual cycle (i.e., migratory connectivity) can reveal the complex ecological and evolutionary relationships that link species and ecosystems across the globe and illuminate where and how limiting factors influence population trends. A growing body of literature continues to identify species that exhibit weak connectivity wherein individuals from distinct breeding areas co-occur during the nonbreeding period. A detailed account of a broadly distributed species exhibiting strong migratory connectivity in which nonbreeding isolation of populations is associated with differential population trends remains undescribed. Here, we present a range-wide assessment of the nonbreeding distribution and migratory connectivity of two broadly dispersed Nearctic-Neotropical migratory songbirds. We used geolocators to track the movements of 70 Vermivora warblers from sites spanning their breeding distribution in eastern North America and identified links between breeding populations and nonbreeding areas. Unlike blue-winged warblers (Vermivora cyanoptera), breeding populations of golden-winged warblers (Vermivora chrysoptera) exhibited strong migratory connectivity, which was associated with historical trends in breeding populations: stable for populations that winter in Central America and declining for those that winter in northern South America.}, } @article {pmid29483272, year = {2018}, author = {Kc, RP and Kunter, M and Mak, V}, title = {The influence of a competition on noncompetitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2716-2721}, pmid = {29483272}, issn = {1091-6490}, mesh = {Adult ; Awareness ; *Competitive Behavior ; Female ; Humans ; Male ; Middle Aged ; Motivation ; Reward ; }, abstract = {We report a series of experimental studies that investigate the influence of a competition on noncompetitors who do not participate in it but are aware of it. Our work is highly relevant across many domains of social life where competitions are prevalent, as it is typical in a competition that the competitors are far outnumbered by these noncompetitors. In our field experiment involving pay-what-you-want entrance at a German zoo (n = 22,886), customers who were aware of a competition over entrance payments, but did not participate in it, paid more than customers who were unaware of the competition. Further experiments provide confirmatory and process evidence for this contagion effect, showing that it is driven by heightened social comparison motivation due to mere awareness of the competition. Moreover, we find evidence that the reward level for the competitors could moderate the contagion effect on the noncompetitors. Even if an individual does not participate in a competition, their behavior can still be influenced by it, and this influence can change with the characteristics of the competition in an intriguing way.}, } @article {pmid29483271, year = {2018}, author = {Al-Rekabi, Z and Contera, S}, title = {Multifrequency AFM reveals lipid membrane mechanical properties and the effect of cholesterol in modulating viscoelasticity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2658-2663}, pmid = {29483271}, issn = {1091-6490}, mesh = {Cell Membrane/*chemistry/metabolism ; Cholesterol/*metabolism ; Elasticity ; Lipid Bilayers/*chemistry/metabolism ; Microscopy, Atomic Force ; Models, Biological ; Viscosity ; }, abstract = {The physical properties of lipid bilayers comprising the cell membrane occupy the current spotlight of membrane biology. Their traditional representation as a passive 2D fluid has gradually been abandoned in favor of a more complex picture: an anisotropic time-dependent viscoelastic biphasic material, capable of transmitting or attenuating mechanical forces that regulate biological processes. In establishing new models, quantitative experiments are necessary when attempting to develop suitable techniques for dynamic measurements. Here, we map both the elastic and viscous properties of the model system 1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) lipid bilayers using multifrequency atomic force microscopy (AFM), namely amplitude modulation-frequency modulation (AM-FM) AFM imaging in an aqueous environment. Furthermore, we investigate the effect of cholesterol (Chol) on the DPPC bilayer in concentrations from 0 to 60%. The AM-AFM quantitative maps demonstrate that at low Chol concentrations, the lipid bilayer displays a distinct phase separation and is elastic, whereas at higher Chol concentration, the bilayer appears homogenous and exhibits both elastic and viscous properties. At low-Chol contents, the Estorage modulus (elastic) dominates. As the Chol insertions increases, higher energy is dissipated; and although the bilayer stiffens (increase in Estorage), the viscous component dominates (Eloss). Our results provide evidence that the lipid bilayer exhibits both elastic and viscous properties that are modulated by the presence of Chol, which may affect the propagation (elastic) or attenuation (viscous) of mechanical signals across the cell membrane.}, } @article {pmid29483270, year = {2018}, author = {Sandeep, S and Ajayamohan, RS and Boos, WR and Sabin, TP and Praveen, V}, title = {Decline and poleward shift in Indian summer monsoon synoptic activity in a warming climate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2681-2686}, pmid = {29483270}, issn = {1091-6490}, abstract = {Cyclonic atmospheric vortices of varying intensity, collectively known as low-pressure systems (LPS), travel northwest across central India and produce more than half of the precipitation received by that fertile region and its ∼600 million inhabitants. Yet, future changes in LPS activity are poorly understood, due in part to inadequate representation of these storms in current climate models. Using a high-resolution atmospheric general circulation model that realistically simulates the genesis distribution of LPS, here we show that Indian monsoon LPS activity declines about 45% by the late 21st century in simulations of a business-as-usual emission scenario. The distribution of LPS genesis shifts poleward as it weakens, with oceanic genesis decreasing by ∼60% and continental genesis increasing by ∼10%; over land the increase in storm counts is accompanied by a shift toward lower storm wind speeds. The weakening and poleward shift of the genesis distribution in a warmer climate are confirmed and attributed, via a statistical model, to the reduction and poleward shift of low-level absolute vorticity over the monsoon region, which in turn are robust features of most coupled model projections. The poleward shift in LPS activity results in an increased frequency of extreme precipitation events over northern India.}, } @article {pmid29483269, year = {2018}, author = {Van Treeck, B and Protter, DSW and Matheny, T and Khong, A and Link, CD and Parker, R}, title = {RNA self-assembly contributes to stress granule formation and defining the stress granule transcriptome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2734-2739}, pmid = {29483269}, issn = {1091-6490}, support = {R01 GM045443/GM/NIGMS NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; T32 GM065103/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cytoplasmic Granules/chemistry/*genetics/metabolism ; RNA/chemistry/*genetics/metabolism ; RNA, Messenger/chemistry/genetics/metabolism ; RNA-Binding Proteins/genetics/metabolism ; Ribonucleoproteins/genetics/metabolism ; Saccharomyces cerevisiae/chemistry/*genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; *Transcriptome ; }, abstract = {Stress granules are higher order assemblies of nontranslating mRNAs and proteins that form when translation initiation is inhibited. Stress granules are thought to form by protein-protein interactions of RNA-binding proteins. We demonstrate RNA homopolymers or purified cellular RNA forms assemblies in vitro analogous to stress granules. Remarkably, under conditions representative of an intracellular stress response, the mRNAs enriched in assemblies from total yeast RNA largely recapitulate the stress granule transcriptome. We suggest stress granules are formed by a summation of protein-protein and RNA-RNA interactions, with RNA self-assembly likely to contribute to other RNP assemblies wherever there is a high local concentration of RNA. RNA assembly in vitro is also increased by GR and PR dipeptide repeats, which are known to increase stress granule formation in cells. Since GR and PR dipeptides are involved in neurodegenerative diseases, this suggests that perturbations increasing RNA-RNA assembly in cells could lead to disease.}, } @article {pmid29483268, year = {2018}, author = {Schulze-Makuch, D and Wagner, D and Kounaves, SP and Mangelsdorf, K and Devine, KG and de Vera, JP and Schmitt-Kopplin, P and Grossart, HP and Parro, V and Kaupenjohann, M and Galy, A and Schneider, B and Airo, A and Frösler, J and Davila, AF and Arens, FL and Cáceres, L and Cornejo, FS and Carrizo, D and Dartnell, L and DiRuggiero, J and Flury, M and Ganzert, L and Gessner, MO and Grathwohl, P and Guan, L and Heinz, J and Hess, M and Keppler, F and Maus, D and McKay, CP and Meckenstock, RU and Montgomery, W and Oberlin, EA and Probst, AJ and Sáenz, JS and Sattler, T and Schirmack, J and Sephton, MA and Schloter, M and Uhl, J and Valenzuela, B and Vestergaard, G and Wörmer, L and Zamorano, P}, title = {Transitory microbial habitat in the hyperarid Atacama Desert.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2670-2675}, pmid = {29483268}, issn = {1091-6490}, mesh = {Bacteria/classification/genetics/*isolation & purification ; Biodiversity ; Desert Climate ; *Ecosystem ; Soil/chemistry ; *Soil Microbiology ; South America ; }, abstract = {Traces of life are nearly ubiquitous on Earth. However, a central unresolved question is whether these traces always indicate an active microbial community or whether, in extreme environments, such as hyperarid deserts, they instead reflect just dormant or dead cells. Although microbial biomass and diversity decrease with increasing aridity in the Atacama Desert, we provide multiple lines of evidence for the presence of an at times metabolically active, microbial community in one of the driest places on Earth. We base this observation on four major lines of evidence: (i) a physico-chemical characterization of the soil habitability after an exceptional rain event, (ii) identified biomolecules indicative of potentially active cells [e.g., presence of ATP, phospholipid fatty acids (PLFAs), metabolites, and enzymatic activity], (iii) measurements of in situ replication rates of genomes of uncultivated bacteria reconstructed from selected samples, and (iv) microbial community patterns specific to soil parameters and depths. We infer that the microbial populations have undergone selection and adaptation in response to their specific soil microenvironment and in particular to the degree of aridity. Collectively, our results highlight that even the hyperarid Atacama Desert can provide a habitable environment for microorganisms that allows them to become metabolically active following an episodic increase in moisture and that once it decreases, so does the activity of the microbiota. These results have implications for the prospect of life on other planets such as Mars, which has transitioned from an earlier wetter environment to today's extreme hyperaridity.}, } @article {pmid29483267, year = {2018}, author = {Chen, Q and Payyavula, RS and Chen, L and Zhang, J and Zhang, C and Turgeon, R}, title = {FLOWERING LOCUS T mRNA is synthesized in specialized companion cells in Arabidopsis and Maryland Mammoth tobacco leaf veins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2830-2835}, pmid = {29483267}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/*metabolism ; Arabidopsis Proteins/*biosynthesis/genetics/metabolism ; Cucurbitaceae/genetics/metabolism ; Flowers/genetics/metabolism ; Galactosyltransferases/genetics/metabolism ; Gene Expression Regulation, Plant ; Phloem/cytology/genetics/*metabolism ; Plant Leaves/genetics/metabolism ; RNA, Messenger/genetics/*metabolism ; Tobacco/genetics/*metabolism ; }, abstract = {Flowering is triggered by the transmission of a mobile protein, FLOWERING LOCUS T (FT), from leaves to the shoot apex. FT originates in the phloem of leaf veins. However, the identity of the FT-synthesizing cells in the phloem is not known. As a result, it has not been possible to determine whether the complex regulatory networks that control FT synthesis involve intercellular communication, as is the case in many aspects of plant development. We demonstrate here that FT in Arabidopsis thaliana and FT orthologs in Maryland Mammoth tobacco (Nicotiana tabacum) are produced in two unique files of phloem companion cells. These FT-activating cells, visualized by fluorescent proteins, also activate the GALACTINOL SYNTHASE (CmGAS1) promoter from melon (Cucumis melo). Ablating the cells by expression of the diphtheria toxin gene driven by the CmGAS1 promoter delays flowering in both Arabidopsis and Maryland Mammoth tobacco. In Arabidopsis, toxin expression reduces expression of FT and flowering-associated genes downstream, but not upstream, of FT Our results indicate that specific companion cells mediate the essential flowering function. Since the identified cells are present in the minor veins of two unrelated dicotyledonous species, this may be a widespread phenomenon.}, } @article {pmid29483266, year = {2018}, author = {Dellibovi-Ragheb, TA and Jhun, H and Goodman, CD and Walters, MS and Ragheb, DRT and Matthews, KA and Rajaram, K and Mishra, S and McFadden, GI and Sinnis, P and Prigge, ST}, title = {Host biotin is required for liver stage development in malaria parasites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2604-E2613}, pmid = {29483266}, issn = {1091-6490}, support = {R01 AI056840/AI/NIAID NIH HHS/United States ; R01 AI065853/AI/NIAID NIH HHS/United States ; R01 AI125534/AI/NIAID NIH HHS/United States ; UL1 RR025005/RR/NCRR NIH HHS/United States ; }, mesh = {Acetyl-CoA Carboxylase/metabolism ; Animals ; Apicoplasts/metabolism ; Biotin/*metabolism ; Carbon-Nitrogen Ligases/metabolism ; Hep G2 Cells ; Host-Parasite Interactions/*physiology ; Humans ; Liver/metabolism/*parasitology ; Malaria/*metabolism/parasitology ; Mice ; Plasmodium/*metabolism ; Protozoan Proteins/metabolism ; }, abstract = {Acetyl-CoA carboxylase (ACC) is a biotin-dependent enzyme that is the target of several classes of herbicides. Malaria parasites contain a plant-like ACC, and this is the only protein predicted to be biotinylated in the parasite. We found that ACC is expressed in the apicoplast organelle in liver- and blood-stage malaria parasites; however, it is activated through biotinylation only in the liver stages. Consistent with this observation, deletion of the biotin ligase responsible for ACC biotinylation does not impede blood-stage growth, but results in late liver-stage developmental defects. Biotin depletion increases the severity of the developmental defects, demonstrating that parasite and host biotin metabolism are required for normal liver-stage progression. This finding may link the development of liver-stage malaria parasites to the nutritional status of the host, as neither the parasite nor the human host can synthesize biotin.}, } @article {pmid29483265, year = {2018}, author = {Wang, Z and Gurule, EE and Brennan, TP and Gerold, JM and Kwon, KJ and Hosmane, NN and Kumar, MR and Beg, SA and Capoferri, AA and Ray, SC and Ho, YC and Hill, AL and Siliciano, JD and Siliciano, RF}, title = {Expanded cellular clones carrying replication-competent HIV-1 persist, wax, and wane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2575-E2584}, pmid = {29483265}, issn = {1091-6490}, support = {UM1 AI126620/AI/NIAID NIH HHS/United States ; DP5 OD019851/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; UM1 AI126603/AI/NIAID NIH HHS/United States ; UM1 AI126611/AI/NIAID NIH HHS/United States ; }, mesh = {*CD4-Positive T-Lymphocytes/immunology/virology ; Cell Proliferation/*physiology ; *HIV Infections/immunology/physiopathology/virology ; *HIV-1/genetics/immunology/pathogenicity/physiology ; *Host-Pathogen Interactions/immunology/physiology ; Humans ; Phylogeny ; Proviruses/physiology ; Time Factors ; Viremia/virology ; Virus Latency/*physiology ; Virus Replication/physiology ; }, abstract = {The latent reservoir for HIV-1 in resting CD4+ T cells is a major barrier to cure. Several lines of evidence suggest that the latent reservoir is maintained through cellular proliferation. Analysis of this proliferative process is complicated by the fact that most infected cells carry defective proviruses. Additional complications are that stimuli that drive T cell proliferation can also induce virus production from latently infected cells and productively infected cells have a short in vivo half-life. In this ex vivo study, we show that latently infected cells containing replication-competent HIV-1 can proliferate in response to T cell receptor agonists or cytokines that are known to induce homeostatic proliferation and that this can occur without virus production. Some cells that have proliferated in response to these stimuli can survive for 7 d while retaining the ability to produce virus. This finding supports the hypothesis that both antigen-driven and cytokine-induced proliferation may contribute to the stability of the latent reservoir. Sequencing of replication-competent proviruses isolated from patients at different time points confirmed the presence of expanded clones and demonstrated that while some clones harboring replication-competent virus persist longitudinally on a scale of years, others wax and wane. A similar pattern is observed in longitudinal sampling of residual viremia in patients. The observed patterns are not consistent with a continuous, cell-autonomous, proliferative process related to the HIV-1 integration site. The fact that the latent reservoir can be maintained, in part, by cellular proliferation without viral reactivation poses challenges to cure.}, } @article {pmid29483264, year = {2018}, author = {Sun, D and Huh, I and Zinzow-Kramer, WM and Maney, DL and Yi, SV}, title = {Rapid regulatory evolution of a nonrecombining autosome linked to divergent behavioral phenotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2794-2799}, pmid = {29483264}, issn = {1091-6490}, support = {R01 MH082833/MH/NIMH NIH HHS/United States ; R21 MH102677/MH/NIMH NIH HHS/United States ; }, mesh = {Aggression ; Animals ; *Behavior, Animal ; *Biological Evolution ; Female ; Male ; Phenotype ; Recombination, Genetic ; Sex Chromosomes/genetics ; Social Behavior ; Sparrows/*genetics/physiology ; }, abstract = {In the white-throated sparrow (Zonotrichia albicollis), the second chromosome bears a striking resemblance to sex chromosomes. First, within each breeding pair of birds, one bird is homozygous for the standard arrangement of the chromosome (ZAL2/ZAL2) and its mate is heterozygous for a different version (ZAL2/ZAL2m). Second, recombination is profoundly suppressed between the two versions, leading to genetic differentiation between them. Third, the ZAL2m version is linked with phenotypic traits, such as bright plumage, high aggression, and low parental behavior, which are usually associated with males. These similarities to sex chromosomes suggest that the evolutionary mechanisms that shape sex chromosomes, in particular genetic degeneration of the heterogametic version due to the suppression of recombination, are likely important in this system as well. Here, we investigated patterns of protein sequence evolution and gene expression evolution between the ZAL2 and ZAL2m chromosomes by whole-genome sequencing and transcriptome analyses. Patterns of protein evolution exhibited only weak signals of genetic degeneration, and few genes harbored signatures of positive selection. We found substantial evidence of transcriptome evolution, such as significant expression divergence between ZAL2 and ZAL2m alleles and signatures of dosage compensation for highly expressed genes. These results suggest that, early in the evolution of heteromorphic chromosomes, gene expression divergence and dosage compensation can prevail before large-scale genetic degeneration. Our results show further that suppression of recombination between heteromorphic chromosomes can lead to the evolution of alternative (sex-like) behavioral phenotypes before substantial genetic degeneration.}, } @article {pmid29483263, year = {2018}, author = {Hester, N and Gray, K}, title = {For Black men, being tall increases threat stereotyping and police stops.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2711-2715}, pmid = {29483263}, issn = {1091-6490}, mesh = {Adult ; African Americans/*psychology ; *Body Height ; European Continental Ancestry Group/psychology ; Female ; Humans ; Male ; Middle Aged ; New York City ; Perception ; *Police/psychology ; Stereotyping ; Workforce ; Young Adult ; }, abstract = {Height seems beneficial for men in terms of salaries and success; however, past research on height examines only White men. For Black men, height may be more costly than beneficial, primarily signaling threat rather than competence. Three studies reveal the downsides of height in Black men. Study 1 analyzes over 1 million New York Police Department stop-and-frisk encounters and finds that tall Black men are especially likely to receive unjustified attention from police. Then, studies 2 and 3 experimentally demonstrate a causal link between perceptions of height and perceptions of threat for Black men, particularly for perceivers who endorse stereotypes that Black people are more threatening than White people. Together, these data reveal that height is sometimes a liability for Black men, particularly in contexts in which threat is salient.}, } @article {pmid29483262, year = {2018}, author = {Raithel, D and Simine, L and Pickel, S and Schötz, K and Panzer, F and Baderschneider, S and Schiefer, D and Lohwasser, R and Köhler, J and Thelakkat, M and Sommer, M and Köhler, A and Rossky, PJ and Hildner, R}, title = {Direct observation of backbone planarization via side-chain alignment in single bulky-substituted polythiophenes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2699-2704}, pmid = {29483262}, issn = {1091-6490}, abstract = {The backbone conformation of conjugated polymers affects, to a large extent, their optical and electronic properties. The usually flexible substituents provide solubility and influence the packing behavior of conjugated polymers in films or in bad solvents. However, the role of the side chains in determining and potentially controlling the backbone conformation, and thus the optical and electronic properties on the single polymer level, is currently under debate. Here, we investigate directly the impact of the side chains by studying the bulky-substituted poly(3-(2,5-dioctylphenyl)thiophene) (PDOPT) and the common poly(3-hexylthiophene) (P3HT), both with a defined molecular weight and high regioregularity, using low-temperature single-chain photoluminescence (PL) spectroscopy and quantum-classical simulations. Surprisingly, the optical transition energy of PDOPT is significantly (∼2,000 cm-1 or 0.25 eV) red-shifted relative to P3HT despite a higher static and dynamic disorder in the former. We ascribe this red shift to a side-chain induced backbone planarization in PDOPT, supported by temperature-dependent ensemble PL spectroscopy. Our atomistic simulations reveal that the bulkier 2,5-dioctylphenyl side chains of PDOPT adopt a clear secondary helical structural motif and thus protect conjugation, i.e., enforce backbone planarity, whereas, for P3HT, this is not the case. These different degrees of planarity in both thiophenes do not result in different conjugation lengths, which we found to be similar. It is rather the stronger electronic coupling between the repeating units in the more planar PDOPT which gives rise to the observed spectral red shift as well as to a reduced calculated electron-hole polarization.}, } @article {pmid29483261, year = {2018}, author = {}, title = {Correction for Meslin et al., Structural complexity and molecular heterogeneity of a butterfly ejaculate reflect a complex history of selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2488}, doi = {10.1073/pnas.1801459115}, pmid = {29483261}, issn = {1091-6490}, } @article {pmid29483260, year = {2018}, author = {Garcin, Y and Deschamps, P and Ménot, G and de Saulieu, G and Schefuß, E and Sebag, D and Dupont, LM and Oslisly, R and Brademann, B and Mbusnum, KG and Onana, JM and Ako, AA and Epp, LS and Tjallingii, R and Strecker, MR and Brauer, A and Sachse, D}, title = {Early anthropogenic impact on Western Central African rainforests 2,600 y ago.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3261-3266}, pmid = {29483260}, issn = {1091-6490}, mesh = {Africa ; *Archaeology ; Cameroon ; *Climate Change ; *Ecosystem ; Humans ; *Rainforest ; Time Factors ; }, abstract = {A potential human footprint on Western Central African rainforests before the Common Era has become the focus of an ongoing controversy. Between 3,000 y ago and 2,000 y ago, regional pollen sequences indicate a replacement of mature rainforests by a forest-savannah mosaic including pioneer trees. Although some studies suggested an anthropogenic influence on this forest fragmentation, current interpretations based on pollen data attribute the ''rainforest crisis'' to climate change toward a drier, more seasonal climate. A rigorous test of this hypothesis, however, requires climate proxies independent of vegetation changes. Here we resolve this controversy through a continuous 10,500-y record of both vegetation and hydrological changes from Lake Barombi in Southwest Cameroon based on changes in carbon and hydrogen isotope compositions of plant waxes. [Formula: see text]13C-inferred vegetation changes confirm a prominent and abrupt appearance of C4 plants in the Lake Barombi catchment, at 2,600 calendar years before AD 1950 (cal y BP), followed by an equally sudden return to rainforest vegetation at 2,020 cal y BP. [Formula: see text]D values from the same plant wax compounds, however, show no simultaneous hydrological change. Based on the combination of these data with a comprehensive regional archaeological database we provide evidence that humans triggered the rainforest fragmentation 2,600 y ago. Our findings suggest that technological developments, including agricultural practices and iron metallurgy, possibly related to the large-scale Bantu expansion, significantly impacted the ecosystems before the Common Era.}, } @article {pmid29483259, year = {2018}, author = {Zhang, L and Marcos, V and Leigh, DA}, title = {Molecular machines with bio-inspired mechanisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9397-9404}, pmid = {29483259}, issn = {1091-6490}, abstract = {The widespread use of molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular machines-which by and large function as switches-and the machines of the macroscopic world, which utilize the synchronized behavior of integrated components to perform more sophisticated tasks than is possible with any individual switch. Should we try to make molecular machines of greater complexity by trying to mimic machines from the macroscopic world or instead apply unfamiliar (and no doubt have to discover or invent currently unknown) mechanisms utilized by biological machines? Here we try to answer that question by exploring some of the advances made to date using bio-inspired machine mechanisms.}, } @article {pmid29483258, year = {2018}, author = {Simmet, K and Zakhartchenko, V and Philippou-Massier, J and Blum, H and Klymiuk, N and Wolf, E}, title = {OCT4/POU5F1 is required for NANOG expression in bovine blastocysts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2770-2775}, pmid = {29483258}, issn = {1091-6490}, mesh = {Animals ; Blastocyst/*metabolism ; CDX2 Transcription Factor/genetics/metabolism ; Cattle/*embryology/genetics/metabolism ; Endoderm/metabolism ; Gene Expression Regulation, Developmental ; Morula/metabolism ; Nanog Homeobox Protein/genetics/*metabolism ; Octamer Transcription Factor-3/genetics/*metabolism ; }, abstract = {Mammalian preimplantation development involves two lineage specifications: first, the CDX2-expressing trophectoderm (TE) and a pluripotent inner cell mass (ICM) are separated during blastocyst formation. Second, the pluripotent epiblast (EPI; expressing NANOG) and the differentiated primitive endoderm (PrE; expressing GATA6) diverge within the ICM. Studies in mice revealed that OCT4/POU5F1 is at the center of a pluripotency regulatory network. To study the role of OCT4 in bovine preimplantation development, we generated OCT4 knockout (KO) fibroblasts by CRISPR-Cas9 and produced embryos by somatic cell nuclear transfer (SCNT). SCNT embryos from nontransfected fibroblasts and embryos produced by in vitro fertilization served as controls. In OCT4 KO morulae (day 5), ∼70% of the nuclei were OCT4 positive, indicating that maternal OCT4 mRNA partially maintains OCT4 protein expression during early development. In contrast, OCT4 KO blastocysts (day 7) lacked OCT4 protein entirely. CDX2 was detected only in TE cells; OCT4 is thus not required to suppress CDX2 in the ICM. Control blastocysts showed a typical salt-and-pepper distribution of NANOG- and GATA6-positive cells in the ICM. In contrast, NANOG was absent or very faint in the ICM of OCT4 KO blastocysts, and no cells expressing exclusively NANOG were observed. This mimics findings in OCT4-deficient human blastocysts but is in sharp contrast to Oct4-null mouse blastocysts, where NANOG persists and PrE development fails. Our study supports bovine embryogenesis as a model for early human development and exemplifies a general strategy for studying the roles of specific genes in embryos of domestic species.}, } @article {pmid29483257, year = {2018}, author = {Luu, J and Palczewski, K}, title = {Human aging and disease: Lessons from age-related macular degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2866-2872}, pmid = {29483257}, issn = {1091-6490}, support = {R01 EY009339/EY/NEI NIH HHS/United States ; R24 EY024864/EY/NEI NIH HHS/United States ; R24 EY027283/EY/NEI NIH HHS/United States ; T32 GM007250/GM/NIGMS NIH HHS/United States ; }, mesh = {*Aging ; Chronic Disease ; Female ; Genetic Therapy ; Humans ; Macular Degeneration/*pathology ; Male ; }, abstract = {Aging is the most significant risk factor associated with chronic disease in humans. The accumulation of genetic damage throughout life leads to a variety of biological aberrations, including disrupted protein homeostasis, metabolic dysfunction, and altered cellular signaling. Such changes ultimately result in cellular senescence, death, or transformation to uncontrolled proliferation, thereby compromising human health. Events contributing to age-dependent physiological decline also occur in the context of hormonal and metabolic changes, affecting interconnected cellular networks. This complexity often confounds the development of effective treatments for aging and age-related diseases. In contrast to monotherapy and polypharmacology, an innovative systems pharmacology approach can identify synergistic combinations of drugs that modulate distinct mechanistic nodes within a network, minimizing off-target side effects and enabling better therapeutic outcomes. G protein-coupled receptors (GPCRs) are particularly good targets for the application of systems pharmacology, because they activate different signal transduction pathways that can culminate in a common response. Here, we describe a systems pharmacology strategy for the treatment of age-related macular degeneration (AMD), a multifactorial chronic disease of the eye. By considering the retina as part of a large, interconnected network, systems pharmacology will enable the identification of combination therapies targeting GPCRs to help restore genomic, proteomic, and endocrine homeostasis. Such an approach can be advantageous in providing drug regimens for the treatment of AMD, while also having broader ramifications for ameliorating adverse effects of chronic, age-related disease in humans.}, } @article {pmid29483256, year = {2018}, author = {Pei, S and Kandula, S and Yang, W and Shaman, J}, title = {Forecasting the spatial transmission of influenza in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2752-2757}, pmid = {29483256}, issn = {1091-6490}, support = {P30 ES009089/ES/NIEHS NIH HHS/United States ; R01 GM100467/GM/NIGMS NIH HHS/United States ; U01 GM110748/GM/NIGMS NIH HHS/United States ; }, mesh = {Forecasting ; Humans ; Influenza, Human/*epidemiology/transmission ; Models, Statistical ; Retrospective Studies ; Seasons ; United States/epidemiology ; }, abstract = {Recurrent outbreaks of seasonal and pandemic influenza create a need for forecasts of the geographic spread of this pathogen. Although it is well established that the spatial progression of infection is largely attributable to human mobility, difficulty obtaining real-time information on human movement has limited its incorporation into existing infectious disease forecasting techniques. In this study, we develop and validate an ensemble forecast system for predicting the spatiotemporal spread of influenza that uses readily accessible human mobility data and a metapopulation model. In retrospective state-level forecasts for 35 US states, the system accurately predicts local influenza outbreak onset,-i.e., spatial spread, defined as the week that local incidence increases above a baseline threshold-up to 6 wk in advance of this event. In addition, the metapopulation prediction system forecasts influenza outbreak onset, peak timing, and peak intensity more accurately than isolated location-specific forecasts. The proposed framework could be applied to emergent respiratory viruses and, with appropriate modifications, other infectious diseases.}, } @article {pmid29483255, year = {2018}, author = {Xu, Y and Shen, H and Yun, X and Gao, F and Chen, Y and Li, B and Liu, J and Ma, J and Wang, X and Liu, X and Tian, C and Xing, B and Tao, S}, title = {Health effects of banning beehive coke ovens and implementation of the ban in China.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2693-2698}, pmid = {29483255}, issn = {1091-6490}, mesh = {Air Pollutants/*analysis/toxicity ; Air Pollution/*legislation & jurisprudence/prevention & control ; Benzo(a)pyrene/analysis/toxicity ; China ; Coal Industry/*instrumentation/*legislation & jurisprudence ; Coke/*analysis/toxicity ; Environmental Monitoring/legislation & jurisprudence ; Humans ; }, abstract = {Environmental legislation and proper implementation are critical in environmental protection. In the past, beehive coke ovens (BCOs) were popular in China, resulting in enormous emissions of benzo[a]pyrene (BaP), a common indicator of carcinogenic polycyclic aromatic hydrocarbons. BCOs were banned by the Coal Law in 1996. Although BCO numbers have declined since the ban, they were not eliminated until 2011 due to poor implementation. Here, we present the results of a quantitative evaluation of the health effects of historical BCO operation, the health benefits of the ban, and the adverse impacts of the poor implementation of the ban. With only limited official statistics available, historical and geospatial data about BCOs were reconstructed based on satellite images. Emission inventories of BaP from BCOs were compiled and used to model atmospheric transport, nonoccupational population exposure, and induced lung cancer risk. We demonstrated that more than 20% of the BaP in ambient air was from BCOs in the peak year. The cumulative nonoccupational excess lung cancer cases associated with BaP from BCOs was 3,500 (±1,500) from 1982 to 2015. If there was no ban, the cases would be as high as 9,290 (±4,300), indicating the significant health benefits of the Coal Law. On the other hand, if the ban had been fully implemented immediately after the law was enforced in 1996, the cumulative cases would be 1,500 (±620), showing the importance of implementing the law.}, } @article {pmid29483254, year = {2018}, author = {Hoinville, T and Wehner, R}, title = {Optimal multiguidance integration in insect navigation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2824-2829}, pmid = {29483254}, issn = {1091-6490}, mesh = {Animals ; Ants/*physiology ; Bees/*physiology ; *Homing Behavior ; Orientation ; Space Perception ; }, abstract = {In the last decades, desert ants have become model organisms for the study of insect navigation. In finding their way, they use two major navigational routines: path integration using a celestial compass and landmark guidance based on sets of panoramic views of the terrestrial environment. It has been claimed that this information would enable the insect to acquire and use a centralized cognitive map of its foraging terrain. Here, we present a decentralized architecture, in which the concurrently operating path integration and landmark guidance routines contribute optimally to the directions to be steered, with "optimal" meaning maximizing the certainty (reliability) of the combined information. At any one time during its journey, the animal computes a path integration (global) vector and landmark guidance (local) vector, in which the length of each vector is proportional to the certainty of the individual estimates. Hence, these vectors represent the limited knowledge that the navigator has at any one place about the direction of the goal. The sum of the global and local vectors indicates the navigator's optimal directional estimate. Wherever applied, this decentralized model architecture is sufficient to simulate the results of quite a number of diverse cue-conflict experiments, which have recently been performed in various behavioral contexts by different authors in both desert ants and honeybees. They include even those experiments that have deliberately been designed by former authors to strengthen the evidence for a metric cognitive map in bees.}, } @article {pmid29483253, year = {2018}, author = {Winter, F and Zhang, N}, title = {Social norm enforcement in ethnically diverse communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2722-2727}, pmid = {29483253}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Cultural Diversity ; Emigration and Immigration ; Ethnic Groups/*psychology ; Female ; Humans ; Male ; Minority Groups/psychology ; Residence Characteristics ; Social Norms/*ethnology ; Young Adult ; }, abstract = {Recent waves of immigration to Western nations have fueled a debate over the consequences of ethnic diversity for social cohesion. One prominent argument in this debate holds that diversity is detrimental to trust and cooperation because individuals in heterogeneous communities face difficulties in enforcing social norms across ethnic lines. We examine this proposition in a field experiment involving real-life interactions among residents of multiethnic German neighborhoods. We find significant ethnic asymmetries in the pattern of norm enforcement: Members of the majority "native" German population are more active in sanctioning norm violations, while ethnic minorities are more likely to find themselves the target of sanctions. We interpret these results in light of prevailing status inequalities between ethnic minorities and the native majority. We further calculate that, as a result of ethnic discrimination, social control is likely to rise in communities with moderate minority population shares.}, } @article {pmid29483252, year = {2018}, author = {Bian, L and Sloane, S and Baillargeon, R}, title = {Infants expect ingroup support to override fairness when resources are limited.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2705-2710}, pmid = {29483252}, issn = {1091-6490}, mesh = {Child, Preschool ; Female ; Group Processes ; Humans ; Infant ; Infant Behavior ; Male ; Morals ; *Psychology, Child ; }, abstract = {Recent research suggests that the foundations of human moral cognition include abstract principles of fairness and ingroup support. We examined which principle 1.5-y-old infants and 2.5-y-old toddlers would prioritize when the two were pitted against each other. In violation-of-expectation tasks, a puppet distributor brought in either two (two-item condition) or three (three-item condition) items and faced two potential recipients, an ingroup and an outgroup puppet. In each condition, the distributor allocated two items in one of three events: She gave one item each to the ingroup and outgroup puppets (equal event), she gave both items to the ingroup puppet (favors-ingroup event), or she gave both items to the outgroup puppet (favors-outgroup event). Children in the two-item condition looked significantly longer at the equal or favors-outgroup event than at the favors-ingroup event, suggesting that when there were only enough items for the group to which the distributor belonged, children detected a violation if she gave any of the items to the outgroup puppet. In the three-item condition, in contrast, children looked significantly longer at the favors-ingroup or favors-outgroup event than at the equal event, suggesting that when there were enough items for all puppets present, children detected a violation if the distributor chose to give two items to one recipient and none to the other, regardless of which recipient was advantaged. Thus, infants and toddlers expected fairness to prevail when there were as many items as puppets, but they expected ingroup support to trump fairness otherwise.}, } @article {pmid29483251, year = {2018}, author = {Abe, K and Katsuno, H and Toriyama, M and Baba, K and Mori, T and Hakoshima, T and Kanemura, Y and Watanabe, R and Inagaki, N}, title = {Grip and slip of L1-CAM on adhesive substrates direct growth cone haptotaxis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2764-2769}, pmid = {29483251}, issn = {1091-6490}, mesh = {Actins/metabolism ; Axons/chemistry/metabolism ; Cell Movement ; *Chemotaxis ; Genetic Diseases, X-Linked/genetics/*metabolism ; Growth Cones/chemistry/*metabolism ; Humans ; Intellectual Disability/genetics/*metabolism ; Laminin/chemistry/metabolism ; Neural Cell Adhesion Molecule L1/*chemistry/genetics/*metabolism ; Spastic Paraplegia, Hereditary/genetics/*metabolism ; }, abstract = {Chemical cues presented on the adhesive substrate direct cell migration, a process termed haptotaxis. To migrate, cells must generate traction forces upon the substrate. However, how cells probe substrate-bound cues and generate directional forces for migration remains unclear. Here, we show that the cell adhesion molecule (CAM) L1-CAM is involved in laminin-induced haptotaxis of axonal growth cones. L1-CAM underwent grip and slip on the substrate. The ratio of the grip state was higher on laminin than on the control substrate polylysine; this was accompanied by an increase in the traction force upon laminin. Our data suggest that the directional force for laminin-induced growth cone haptotaxis is generated by the grip and slip of L1-CAM on the substrates, which occur asymmetrically under the growth cone. This mechanism is distinct from the conventional cell signaling models for directional cell migration. We further show that this mechanism is disrupted in a human patient with L1-CAM syndrome, suffering corpus callosum agenesis and corticospinal tract hypoplasia.}, } @article {pmid29483250, year = {2018}, author = {Goldstein, P and Weissman-Fogel, I and Dumas, G and Shamay-Tsoory, SG}, title = {Brain-to-brain coupling during handholding is associated with pain reduction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2528-E2537}, pmid = {29483250}, issn = {1091-6490}, mesh = {Adult ; Brain/*physiology ; Brain Chemistry ; Electroencephalography ; Empathy ; Family Characteristics ; Female ; Hand/*physiology ; Humans ; Interpersonal Relations ; Male ; Pain/physiopathology/*psychology ; Pain Measurement ; Young Adult ; }, abstract = {The mechanisms underlying analgesia related to social touch are not clear. While recent research highlights the role of the empathy of the observer to pain relief in the target, the contribution of social interaction to analgesia is unknown. The current study examines brain-to-brain coupling during pain with interpersonal touch and tests the involvement of interbrain synchrony in pain alleviation. Romantic partners were assigned the roles of target (pain receiver) and observer (pain observer) under pain-no-pain and touch-no-touch conditions concurrent with EEG recording. Brain-to-brain coupling in alpha-mu band (8-12 Hz) was estimated by a three-step multilevel analysis procedure based on running window circular correlation coefficient and post hoc power of the findings was calculated using simulations. Our findings indicate that hand-holding during pain administration increases brain-to-brain coupling in a network that mainly involves the central regions of the pain target and the right hemisphere of the pain observer. Moreover, brain-to-brain coupling in this network was found to correlate with analgesia magnitude and observer's empathic accuracy. These findings indicate that brain-to-brain coupling may be involved in touch-related analgesia.}, } @article {pmid29483249, year = {2018}, author = {Culik, RM and Sekhar, A and Nagesh, J and Deol, H and Rumfeldt, JAO and Meiering, EM and Kay, LE}, title = {Effects of maturation on the conformational free-energy landscape of SOD1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2546-E2555}, pmid = {29483249}, issn = {1091-6490}, support = {IRSC 0148000645//CIHR/Canada ; }, mesh = {Copper/chemistry/metabolism ; Dimerization ; Entropy ; Humans ; Oxidation-Reduction ; Protein Conformation ; *Protein Folding ; Superoxide Dismutase-1/*chemistry/metabolism ; Zinc/chemistry/metabolism ; }, abstract = {Amyotrophic lateral sclerosis (ALS) is a devastating fatal syndrome characterized by very rapid degeneration of motor neurons. A leading hypothesis is that ALS is caused by toxic protein misfolding and aggregation, as also occurs in many other neurodegenerative disorders, such as prion, Alzheimer's, Parkinson's, and Huntington's diseases. A prominent cause of familial ALS is mutations in the protein superoxide dismutase (SOD1), which promote the formation of misfolded SOD1 conformers that are prone to aberrant interactions both with each other and with other cellular components. We have shown previously that immature SOD1, lacking bound Cu and Zn metal ions and the intrasubunit disulfide bond (apoSOD12SH), has a rugged free-energy surface (FES) and exchanges with four other conformations (excited states) that have millisecond lifetimes and sparse populations on the order of a few percent. Here, we examine further states of SOD1 along its maturation pathway, as well as those off-pathway resulting from metal loss that have been observed in proteinaceous inclusions. Metallation and disulfide bond formation lead to structural transformations including local ordering of the electrostatic loop and native dimerization that are observed in rare conformers of apoSOD12SH; thus, SOD1 maturation may occur via a population-switch mechanism whereby posttranslational modifications select for preexisting structures on the FES. Metallation and oxidation of SOD1 stabilize the native, mature conformation and decrease the number of detected excited conformational states, suggesting that it is the immature forms of the protein that contribute to misfolded conformations in vivo rather than the highly stable enzymatically active dimer.}, } @article {pmid29483248, year = {2018}, author = {Chen, M and Shu, J and Xie, X and Tan, D and Mao, HK}, title = {Natural diamond formation by self-redox of ferromagnesian carbonate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2676-2680}, pmid = {29483248}, issn = {1091-6490}, abstract = {Formation of natural diamonds requires the reduction of carbon to its bare elemental form, and pressures (P) greater than 5 GPa to cross the graphite-diamond transition boundary. In a study of shocked ferromagnesian carbonate at the Xiuyan impact crater, we found that the impact pressure-temperature (P-T) of 25-45 GPa and 800-900 °C were sufficient to decompose ankerite Ca(Fe2+,Mg)(CO3)2 to form diamond in the absence of another reductant. The carbonate self-reduced to diamond by concurrent oxidation of Fe2+ to Fe3+ to form a high-P polymorph of magnesioferrite, MgFe3+2O4 Discovery of the subsolidus carbonate self-reduction mechanism indicates that diamonds could be ubiquitously present as a dominant host for carbon in the Earth's lower mantle.}, } @article {pmid29483247, year = {2018}, author = {Palkopoulou, E and Lipson, M and Mallick, S and Nielsen, S and Rohland, N and Baleka, S and Karpinski, E and Ivancevic, AM and To, TH and Kortschak, RD and Raison, JM and Qu, Z and Chin, TJ and Alt, KW and Claesson, S and Dalén, L and MacPhee, RDE and Meller, H and Roca, AL and Ryder, OA and Heiman, D and Young, S and Breen, M and Williams, C and Aken, BL and Ruffier, M and Karlsson, E and Johnson, J and Di Palma, F and Alfoldi, J and Adelson, DL and Mailund, T and Munch, K and Lindblad-Toh, K and Hofreiter, M and Poinar, H and Reich, D}, title = {A comprehensive genomic history of extinct and living elephants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2566-E2574}, pmid = {29483247}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; R01 GM100233/GM/NIGMS NIH HHS/United States ; U54 HG003067/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; WT098051//Wellcome Trust/United Kingdom ; WT108749/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Elephants/classification/*genetics ; Evolution, Molecular ; Extinction, Biological ; Fossils ; Gene Flow ; Genome ; Genomics/history ; History, Ancient ; Mammoths/classification/*genetics ; Mastodons/classification/*genetics ; Phylogeny ; }, abstract = {Elephantids are the world's most iconic megafaunal family, yet there is no comprehensive genomic assessment of their relationships. We report a total of 14 genomes, including 2 from the American mastodon, which is an extinct elephantid relative, and 12 spanning all three extant and three extinct elephantid species including an ∼120,000-y-old straight-tusked elephant, a Columbian mammoth, and woolly mammoths. Earlier genetic studies modeled elephantid evolution via simple bifurcating trees, but here we show that interspecies hybridization has been a recurrent feature of elephantid evolution. We found that the genetic makeup of the straight-tusked elephant, previously placed as a sister group to African forest elephants based on lower coverage data, in fact comprises three major components. Most of the straight-tusked elephant's ancestry derives from a lineage related to the ancestor of African elephants while its remaining ancestry consists of a large contribution from a lineage related to forest elephants and another related to mammoths. Columbian and woolly mammoths also showed evidence of interbreeding, likely following a latitudinal cline across North America. While hybridization events have shaped elephantid history in profound ways, isolation also appears to have played an important role. Our data reveal nearly complete isolation between the ancestors of the African forest and savanna elephants for ∼500,000 y, providing compelling justification for the conservation of forest and savanna elephants as separate species.}, } @article {pmid29483246, year = {2018}, author = {Branas, CC and South, E and Kondo, MC and Hohl, BC and Bourgois, P and Wiebe, DJ and MacDonald, JM}, title = {Citywide cluster randomized trial to restore blighted vacant land and its effects on violence, crime, and fear.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2946-2951}, pmid = {29483246}, issn = {1091-6490}, support = {R01 AA020331/AA/NIAAA NIH HHS/United States ; R01 DA010164/DA/NIDA NIH HHS/United States ; R01 DA037820/DA/NIDA NIH HHS/United States ; R49CE002474//ACL HHS/United States ; }, mesh = {*Cities ; Cluster Analysis ; Crime/*prevention & control/statistics & numerical data ; Environmental Restoration and Remediation ; *Fear ; Humans ; Recreation ; Residence Characteristics ; United States ; *Urban Renewal ; Violence/*prevention & control/statistics & numerical data ; }, abstract = {Vacant and blighted urban land is a widespread and potentially risky environmental condition encountered by millions of people on a daily basis. About 15% of the land in US cities is deemed vacant or abandoned, an area roughly the size of Switzerland. In a citywide cluster randomized controlled trial, we investigated the effects of standardized, reproducible interventions that restore vacant land on the commission of violence, crime, and the perceptions of fear and safety. Quantitative and ethnographic analyses were included in a mixed-methods approach to more fully test and explicate our findings. A total of 541 randomly sampled vacant lots were randomly assigned into treatment and control study arms; outcomes from police and 445 randomly sampled participants were analyzed over a 38-month study period. Participants living near treated vacant lots reported significantly reduced perceptions of crime (-36.8%, P < 0.05), vandalism (-39.3%, P < 0.05), and safety concerns when going outside their homes (-57.8%, P < 0.05), as well as significantly increased use of outside spaces for relaxing and socializing (75.7%, P < 0.01). Significant reductions in crime overall (-13.3%, P < 0.01), gun violence (-29.1%, P < 0.001), burglary (-21.9%, P < 0.001), and nuisances (-30.3%, P < 0.05) were also found after the treatment of vacant lots in neighborhoods below the poverty line. Blighted and vacant urban land affects people's perceptions of safety, and their actual, physical safety. Restoration of this land can be an effective and scalable infrastructure intervention for gun violence, crime, and fear in urban neighborhoods.}, } @article {pmid29483245, year = {2018}, author = {Nave, LE and Domke, GM and Hofmeister, KL and Mishra, U and Perry, CH and Walters, BF and Swanston, CW}, title = {Reforestation can sequester two petagrams of carbon in US topsoils in a century.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2776-2781}, pmid = {29483245}, issn = {1091-6490}, mesh = {Carbon/*analysis/metabolism ; Environmental Monitoring ; Forests ; Greenhouse Effect ; Soil/*chemistry ; Trees/growth & development/metabolism ; United States ; }, abstract = {Soils are Earth's largest terrestrial carbon (C) pool, and their responsiveness to land use and management make them appealing targets for strategies to enhance C sequestration. Numerous studies have identified practices that increase soil C, but their inferences are often based on limited data extrapolated over large areas. Here, we combine 15,000 observations from two national-level databases with remote sensing information to address the impacts of reforestation on the sequestration of C in topsoils (uppermost mineral soil horizons). We quantify C stocks in cultivated, reforesting, and natural forest topsoils; rates of C accumulation in reforesting topsoils; and their contribution to the US forest C sink. Our results indicate that reforestation increases topsoil C storage, and that reforesting lands, currently occupying >500,000 km2 in the United States, will sequester a cumulative 1.3-2.1 Pg C within a century (13-21 Tg C·y-1). Annually, these C gains constitute 10% of the US forest sector C sink and offset 1% of all US greenhouse gas emissions.}, } @article {pmid29483244, year = {2018}, author = {Mehra, A and Maloof, A}, title = {Multiscale approach reveals that Cloudina aggregates are detritus and not in situ reef constructions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2519-E2527}, pmid = {29483244}, issn = {1091-6490}, mesh = {Animals ; Coral Reefs ; Fossils/history ; History, Ancient ; Invertebrates/chemistry/*growth & development ; }, abstract = {The earliest metazoans capable of biomineralization appeared during the late Ediacaran Period (635-541 Ma) in strata associated with shallow water microbial reefs. It has been suggested that some Ediacaran microbial reefs were dominated (and possibly built) by an abundant and globally distributed tubular organism known as Cloudina If true, this interpretation implies that metazoan framework reef building-a complex behavior that is responsible for some of the largest bioconstructions and most diverse environments in modern oceans-emerged much earlier than previously thought. Here, we present 3D reconstructions of Cloudina populations, produced using an automated serial grinding and imaging system coupled with a recently developed neural network image classifier. Our reconstructions show that Cloudina aggregates are composed of transported remains while detailed field observations demonstrate that the studied reef outcrops contain only detrital Cloudina buildups, suggesting that Cloudina played a minor role in Ediacaran reef systems. These techniques have wide applicability to problems that require 3D reconstructions where physical separation is impossible and a lack of density contrast precludes tomographic imaging techniques.}, } @article {pmid29483243, year = {2018}, author = {Wang, PJ and Ferralis, N and Conway, C and Grossman, JC and Edelman, ER}, title = {Strain-induced accelerated asymmetric spatial degradation of polymeric vascular scaffolds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2640-2645}, pmid = {29483243}, issn = {1091-6490}, support = {R01 GM049039/GM/NIGMS NIH HHS/United States ; }, mesh = {Absorbable Implants ; Animals ; Biocompatible Materials/chemistry ; Blood Vessels/growth & development ; Humans ; Polyesters/chemistry ; Polymers/*chemistry ; Spectrum Analysis, Raman ; Tissue Scaffolds/*chemistry ; }, abstract = {Polymer-based bioresorbable scaffolds (BRS) seek to eliminate long-term complications of metal stents. However, current BRS designs bear substantially higher incidence of clinical failures, especially thrombosis, compared with metal stents. Research strategies inherited from metal stents fail to consider polymer microstructures and dynamics--issues critical to BRS. Using Raman spectroscopy, we demonstrate microstructural heterogeneities within polymeric scaffolds arising from integrated strain during fabrication and implantation. Stress generated from crimping and inflation causes loss of structural integrity even before chemical degradation, and the induced differences in crystallinity and polymer alignment across scaffolds lead to faster degradation in scaffold cores than on the surface, which further enlarge localized deformation. We postulate that these structural irregularities and asymmetric material degradation present a response to strain and thereby clinical performance different from metal stents. Unlike metal stents which stay patent and intact until catastrophic fracture, BRS exhibit loss of structural integrity almost immediately upon crimping and expansion. Irregularities in microstructure amplify these effects and can have profound clinical implications. Therefore, polymer microstructure should be considered in earliest design stages of resorbable devices, and fabrication processes must be well-designed with microscopic perspective.}, } @article {pmid29483242, year = {2018}, author = {Sequeira, AMM and Rodríguez, JP and Eguíluz, VM and Harcourt, R and Hindell, M and Sims, DW and Duarte, CM and Costa, DP and Fernández-Gracia, J and Ferreira, LC and Hays, GC and Heupel, MR and Meekan, MG and Aven, A and Bailleul, F and Baylis, AMM and Berumen, ML and Braun, CD and Burns, J and Caley, MJ and Campbell, R and Carmichael, RH and Clua, E and Einoder, LD and Friedlaender, A and Goebel, ME and Goldsworthy, SD and Guinet, C and Gunn, J and Hamer, D and Hammerschlag, N and Hammill, M and Hückstädt, LA and Humphries, NE and Lea, MA and Lowther, A and Mackay, A and McHuron, E and McKenzie, J and McLeay, L and McMahon, CR and Mengersen, K and Muelbert, MMC and Pagano, AM and Page, B and Queiroz, N and Robinson, PW and Shaffer, SA and Shivji, M and Skomal, GB and Thorrold, SR and Villegas-Amtmann, S and Weise, M and Wells, R and Wetherbee, B and Wiebkin, A and Wienecke, B and Thums, M}, title = {Convergence of marine megafauna movement patterns in coastal and open oceans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3072-3077}, pmid = {29483242}, issn = {1091-6490}, mesh = {*Animal Migration ; Animals ; *Databases, Factual ; Ecosystem ; *Oceans and Seas ; *Vertebrates ; }, abstract = {The extent of increasing anthropogenic impacts on large marine vertebrates partly depends on the animals' movement patterns. Effective conservation requires identification of the key drivers of movement including intrinsic properties and extrinsic constraints associated with the dynamic nature of the environments the animals inhabit. However, the relative importance of intrinsic versus extrinsic factors remains elusive. We analyze a global dataset of ∼2.8 million locations from >2,600 tracked individuals across 50 marine vertebrates evolutionarily separated by millions of years and using different locomotion modes (fly, swim, walk/paddle). Strikingly, movement patterns show a remarkable convergence, being strongly conserved across species and independent of body length and mass, despite these traits ranging over 10 orders of magnitude among the species studied. This represents a fundamental difference between marine and terrestrial vertebrates not previously identified, likely linked to the reduced costs of locomotion in water. Movement patterns were primarily explained by the interaction between species-specific traits and the habitat(s) they move through, resulting in complex movement patterns when moving close to coasts compared with more predictable patterns when moving in open oceans. This distinct difference may be associated with greater complexity within coastal microhabitats, highlighting a critical role of preferred habitat in shaping marine vertebrate global movements. Efforts to develop understanding of the characteristics of vertebrate movement should consider the habitat(s) through which they move to identify how movement patterns will alter with forecasted severe ocean changes, such as reduced Arctic sea ice cover, sea level rise, and declining oxygen content.}, } @article {pmid29482873, year = {2018}, author = {Salicini, I and Ibáñez, C and Juste, J}, title = {Corrigendum to "Multilocus phylogeny and species delimitation within the Natterer's bat species complex in the Western Palearctic" [Molecular Phylogenetics and Evolution 61 (2011) 888-898].}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {391-392}, doi = {10.1016/j.ympev.2018.01.011}, pmid = {29482873}, issn = {1095-9513}, } @article {pmid29482872, year = {2018}, author = {Sands, AF and Apanaskevich, DA and Matthee, S and Horak, IG and Harrison, A and Karim, S and Mohammad, MK and Mumcuoglu, KY and Rajakaruna, RS and Santos-Silva, MM and Kamani, J and Matthee, CA}, title = {Corrigendum to Effects of tectonics and large scale climatic changes on the evolutionary history of Hyalomma ticks Molecular Phylogenetics and Evolution (2017) 114:153-165.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {390}, doi = {10.1016/j.ympev.2018.01.010}, pmid = {29482872}, issn = {1095-9513}, } @article {pmid29482661, year = {2018}, author = {Han, M and Hao, L and Lin, Y and Li, F and Wang, J and Yang, H and Xiao, L and Kristiansen, K and Jia, H and Li, J}, title = {A novel affordable reagent for room temperature storage and transport of fecal samples for metagenomic analyses.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {43}, pmid = {29482661}, issn = {2049-2618}, support = {2017YFC0909700//National Key Research and Development Program of China/International ; 31601073//National Natural Science Foundation of China/International ; JSGG20160229172752028//Shenzhen Municipal Government of China/International ; JCYJ20160229172757249//Shenzhen Municipal Government of China/International ; }, mesh = {Bacteria/*genetics/metabolism ; DNA, Bacterial/*genetics ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Humans ; Specimen Handling/*methods ; Temperature ; }, abstract = {BACKGROUND: The number of large-scale studies on the gut microbiota in human cohorts is rapidly increasing. However, the few and expensive options for storage of fecal samples at room temperature have been an obstacle for large-scale metagenomic studies and the development of clinical/commercial personal metagenomic sequencing.

RESULTS: In this study, we systematically tested a novel N-octylpyridinium bromide-based fecal sample preservation method and compared it with other currently used storage methods. We found that the N-octylpyridinium bromide-based method enabled preservation of the bacterial composition in fecal samples transported and stored at room temperature for up to at least 14 days.

CONCLUSIONS: We describe a novel chemical stabilizer that allows cost-effective transportation and storage at room temperature for several days with preservation of bacterial composition. This method will facilitate sample collection even in remote area and also enable transport via normal commercial transportation routes.}, } @article {pmid29482646, year = {2018}, author = {Louca, S and Doebeli, M and Parfrey, LW}, title = {Correcting for 16S rRNA gene copy numbers in microbiome surveys remains an unsolved problem.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {41}, pmid = {29482646}, issn = {2049-2618}, mesh = {Archaea/classification/*genetics ; Bacteria/classification/*genetics ; Base Sequence/genetics ; Gene Dosage/*genetics ; Genome, Bacterial/genetics ; Humans ; Metagenomics/methods ; Microbiota/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA ; }, abstract = {The 16S ribosomal RNA gene is the most widely used marker gene in microbial ecology. Counts of 16S sequence variants, often in PCR amplicons, are used to estimate proportions of bacterial and archaeal taxa in microbial communities. Because different organisms contain different 16S gene copy numbers (GCNs), sequence variant counts are biased towards clades with greater GCNs. Several tools have recently been developed for predicting GCNs using phylogenetic methods and based on sequenced genomes, in order to correct for these biases. However, the accuracy of those predictions has not been independently assessed. Here, we systematically evaluate the predictability of 16S GCNs across bacterial and archaeal clades, based on ∼ 6,800 public sequenced genomes and using several phylogenetic methods. Further, we assess the accuracy of GCNs predicted by three recently published tools (PICRUSt, CopyRighter, and PAPRICA) over a wide range of taxa and for 635 microbial communities from varied environments. We find that regardless of the phylogenetic method tested, 16S GCNs could only be accurately predicted for a limited fraction of taxa, namely taxa with closely to moderately related representatives (≲15% divergence in the 16S rRNA gene). Consistent with this observation, we find that all considered tools exhibit low predictive accuracy when evaluated against completely sequenced genomes, in some cases explaining less than 10% of the variance. Substantial disagreement was also observed between tools (R2<0.5) for the majority of tested microbial communities. The nearest sequenced taxon index (NSTI) of microbial communities, i.e., the average distance to a sequenced genome, was a strong predictor for the agreement between GCN prediction tools on non-animal-associated samples, but only a moderate predictor for animal-associated samples. We recommend against correcting for 16S GCNs in microbiome surveys by default, unless OTUs are sufficiently closely related to sequenced genomes or unless a need for true OTU proportions warrants the additional noise introduced, so that community profiles remain interpretable and comparable between studies.}, } @article {pmid29482639, year = {2018}, author = {Marotz, CA and Sanders, JG and Zuniga, C and Zaramela, LS and Knight, R and Zengler, K}, title = {Improving saliva shotgun metagenomics by chemical host DNA depletion.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {42}, pmid = {29482639}, issn = {2049-2618}, support = {R21 AR071731/AR/NIAMS NIH HHS/United States ; AR071731/AR/NIAMS NIH HHS/United States ; n/a//Center for Microbiome Innovation/International ; }, mesh = {Azides/*chemistry ; Bacteria/genetics ; DNA/*chemistry ; Fungi/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics/*methods ; Microbiota/*genetics ; Propidium/*analogs & derivatives/chemistry ; Saliva/*microbiology ; Sequence Analysis, DNA ; Viruses/genetics ; }, abstract = {BACKGROUND: Shotgun sequencing of microbial communities provides in-depth knowledge of the microbiome by cataloging bacterial, fungal, and viral gene content within a sample, providing an advantage over amplicon sequencing approaches that assess taxonomy but not function and are taxonomically limited. However, mammalian DNA can dominate host-derived samples, obscuring changes in microbial populations because few DNA sequence reads are from the microbial component. We developed and optimized a novel method for enriching microbial DNA from human oral samples and compared its efficiency and potential taxonomic bias with commercially available kits.

RESULTS: Three commercially available host depletion kits were directly compared with size filtration and a novel method involving osmotic lysis and treatment with propidium monoazide (lyPMA) in human saliva samples. We evaluated the percentage of shotgun metagenomic sequencing reads aligning to the human genome, and taxonomic biases of those not aligning, compared to untreated samples. lyPMA was the most efficient method of removing host-derived sequencing reads compared to untreated sample (8.53 ± 0.10% versus 89.29 ± 0.03%). Furthermore, lyPMA-treated samples exhibit the lowest taxonomic bias compared to untreated samples.

CONCLUSION: Osmotic lysis followed by PMA treatment is a cost-effective, rapid, and robust method for enriching microbial sequence data in shotgun metagenomics from fresh and frozen saliva samples and may be extensible to other host-derived sample types.}, } @article {pmid29482623, year = {2018}, author = {Kimble, KM and Dickinson, SE and Biase, FH}, title = {Extraction of total RNA from single-oocytes and single-cell mRNA sequencing of swine oocytes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {155}, pmid = {29482623}, issn = {1756-0500}, mesh = {Animals ; Cattle ; Female ; *Oocytes ; Sequence Analysis, RNA/*methods ; Swine ; }, abstract = {OBJECTIVE: Analyses of single oocytes are essential for a fine dissection of molecular features governing developmental competence. We adapted the phenol-chloroform procedure for the purification of total RNA from single oocytes.

RESULTS: Key modifications include the use of Phasemaker™ tubes, a second chloroform wash of the aqueous phase, and the precipitation of the RNA with glyclogen in a 200 μl micro-centrifuge tube. Assessment of the RNA profile from single oocytes showed distinct peaks for 18S and 28S ribosomal subunits. This approach permitted the extraction of small RNAs from single oocytes, which was evident by the presence of 5S and 5.8S rRNAs and tRNAs around 122-123 nucleotides long. The amplification of polyadenylated RNA resulted in detectable DNA products ranging from ~ 500 to ~ 5000 nucleotides. We used the amplified DNA as template for single-cell mRNA-sequencing of five swine oocytes and quantified the expression levels of 9587 genes with complete coverage of transcripts over 10,000 nucleotides in length. The coverage was similar in all oocytes sequenced, demonstrating consistent high RNA quality across samples. We isolated total RNA from single oocytes and demonstrated that the quality was appropriate for single-cell mRNA-sequencing.}, } @article {pmid29482606, year = {2018}, author = {Fujita, T and Yuno, M and Fujii, H}, title = {enChIP systems using different CRISPR orthologues and epitope tags.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {154}, pmid = {29482606}, issn = {1756-0500}, support = {15K06895//Ministry of Education, Culture, Sports, Science and Technology/ ; 15H04329//Ministry of Education, Culture, Sports, Science and Technology/ ; 15H01354//Ministry of Education, Culture, Sports, Science and Technology/ ; }, mesh = {*CRISPR-Cas Systems ; Chromatin Immunoprecipitation/*methods ; *Clustered Regularly Interspaced Short Palindromic Repeats ; DNA, Bacterial/*genetics ; *Epitopes ; Staphylococcus aureus/*genetics ; }, abstract = {OBJECTIVE: Previously, we developed the engineered DNA-binding molecule-mediated chromatin immunoprecipitation (enChIP) technology, which isolates specific genomic regions while preserving their molecular interactions. In enChIP, the locus of interest is tagged with engineered DNA-binding molecules such as the clustered regularly interspaced short palindromic repeats (CRISPR) system, consisting of a catalytically inactive form of Cas9 (dCas9) and guide RNA, followed by affinity purification of the tagged locus to allow identification of associated molecules. In our previous studies, we used a 3xFLAG-tagged CRISPR system from Streptococcus pyogenes (S. pyogenes). In this study, to increase the flexibility of enChIP, we used the CRISPR system from Staphylococcus aureus (S. aureus) along with different epitope tags.

RESULTS: We generated a plasmid expressing S. aureus dCas9 (Sa-dCas9) fused to a nuclear localization signal (NLS) and a 3xFLAG-tag (Sa-dCas9-3xFLAG). The yields of enChIP using Sa-dCas9-3xFLAG were comparable to those using S. pyogenes dCas9 fused with an NLS and a 3xFLAG-tag (3xFLAG-Sp-dCas9). We also generated another enChIP system using Sp-dCas9 fused with an NLS and a 2xAM-tag (Sp-dCas9-2xAM). We obtained high enChIP yields using this system as well. Our findings indicate that these tools will increase the flexibility of enChIP analysis.}, } @article {pmid29482602, year = {2018}, author = {Mbatha, JN and Galappaththi-Arachchige, HN and Mtshali, A and Taylor, M and Ndhlovu, PD and Kjetland, EF and Baay, MFD and Mkhize-Kwitshana, ZL}, title = {Correction to: Self-sampling for human papillomavirus testing among rural young women of KwaZulu-Natal, South Africa.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {153}, doi = {10.1186/s13104-018-3252-6}, pmid = {29482602}, issn = {1756-0500}, abstract = {Following publication of the original article [1], one of the authors reported that his name had been spelled incorrectly. It should be Galappaththi-Arachchige, not Galapaththi-Arachchige.}, } @article {pmid29482592, year = {2018}, author = {Da Gama Duarte, J and Goosen, RW and Lawry, PJ and Blackburn, JM}, title = {PMA: Protein Microarray Analyser, a user-friendly tool for data processing and normalization.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {156}, pmid = {29482592}, issn = {1756-0500}, support = {64760//National Research Foundation/ ; }, mesh = {Humans ; Protein Array Analysis/*methods/*standards ; }, abstract = {OBJECTIVE: Protein microarrays provide a high-throughput platform to measure protein interactions and associated functions, and can aid in the discovery of cancer biomarkers. The resulting protein microarray data can however be subject to systematic bias and noise, thus requiring a robust data processing, normalization and analysis pipeline to ensure high quality and robust results. To date, a comprehensive data processing pipeline is yet to be developed. Furthermore, a lack of analysis consistency is evident amongst different research groups, thereby impeding collaborative data consolidation and comparison. Thus, we sought to develop an accessible data processing tool using methods that are generalizable to the protein microarray field and which can be adapted to individual array layouts with minimal software engineering expertise.

RESULTS: We developed an improved version of a previously developed pipeline of protein microarray data processing and implemented it as an open source software tool, with particular focus on widening its use and applicability. The Protein Microarray Analyser software presented here includes the following tools: (1) neighbourhood background correction, (2) net intensity correction, (3) user-defined noise threshold, (4) user-defined CV threshold amongst replicates and (5) assay controls, (6) composite 'pin-to-pin' normalization amongst sub-arrays, and (7) 'array-to-array' normalization amongst whole arrays.}, } @article {pmid29482548, year = {2018}, author = {Guo, L and Accorsi, A and He, S and Guerrero-Hernández, C and Sivagnanam, S and McKinney, S and Gibson, M and Sánchez Alvarado, A}, title = {An adaptable chromosome preparation methodology for use in invertebrate research organisms.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {25}, pmid = {29482548}, issn = {1741-7007}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {BACKGROUND: The ability to efficiently visualize and manipulate chromosomes is fundamental to understanding the genome architecture of organisms. Conventional chromosome preparation protocols developed for mammalian cells and those relying on species-specific conditions are not suitable for many invertebrates. Hence, a simple and inexpensive chromosome preparation protocol, adaptable to multiple invertebrate species, is needed.

RESULTS: We optimized a chromosome preparation protocol and applied it to several planarian species (phylum Platyhelminthes), the freshwater apple snail Pomacea canaliculata (phylum Mollusca), and the starlet sea anemone Nematostella vectensis (phylum Cnidaria). We demonstrated that both mitotically active adult tissues and embryos can be used as sources of metaphase chromosomes, expanding the potential use of this technique to invertebrates lacking cell lines and/or with limited access to the complete life cycle. Simple hypotonic treatment with deionized water was sufficient for karyotyping; growing cells in culture was not necessary. The obtained karyotypes allowed the identification of differences in ploidy and chromosome architecture among otherwise morphologically indistinguishable organisms, as in the case of a mixed population of planarians collected in the wild. Furthermore, we showed that in all tested organisms representing three different phyla this protocol could be effectively coupled with downstream applications, such as chromosome fluorescent in situ hybridization.

CONCLUSIONS: Our simple and inexpensive chromosome preparation protocol can be readily adapted to new invertebrate research organisms to accelerate the discovery of novel genomic patterns across the branches of the tree of life.}, } @article {pmid29482522, year = {2018}, author = {Danks, GB and Navratilova, P and Lenhard, B and Thompson, EM}, title = {Distinct core promoter codes drive transcription initiation at key developmental transitions in a marine chordate.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {164}, doi = {10.1186/s12864-018-4504-5}, pmid = {29482522}, issn = {1471-2164}, support = {MC_UP_1102/1//Medical Research Council/United Kingdom ; 183690/S10//Norges Forskningsråd/International ; 133335/V40//Norges Forskningsråd/International ; }, mesh = {Animals ; Chordata/*genetics/metabolism ; DNA Methylation ; *Gene Expression Regulation, Developmental ; Genome ; Nucleosomes/metabolism ; Promoter Regions, Genetic ; Spermatogenesis ; TATA Box ; *Transcription Initiation Site ; Transcription, Genetic ; }, abstract = {BACKGROUND: Development is largely driven by transitions between transcriptional programs. The initiation of transcription at appropriate sites in the genome is a key component of this and yet few rules governing selection are known. Here, we used cap analysis of gene expression (CAGE) to generate bp-resolution maps of transcription start sites (TSSs) across the genome of Oikopleura dioica, a member of the closest living relatives to vertebrates.

RESULTS: Our TSS maps revealed promoter features in common with vertebrates, as well as striking differences, and uncovered key roles for core promoter elements in the regulation of development. During spermatogenesis there is a genome-wide shift in mode of transcription initiation characterized by a novel core promoter element. This element was associated with > 70% of male-specific transcription, including the use of cryptic internal promoters within operons. In many cases this led to the exclusion of trans-splice sites, revealing a novel mechanism for regulating which mRNAs receive the spliced leader. Binding of the cell cycle regulator, E2F1, is enriched at the TSS of maternal genes in endocycling nurse nuclei. In addition, maternal promoters lack the TATA-like element found in zebrafish and have broad, rather than sharp, architectures with ordered nucleosomes. Promoters of ribosomal protein genes lack the highly conserved TCT initiator. We also report an association between DNA methylation on transcribed gene bodies and the TATA-box.

CONCLUSIONS: Our results reveal that distinct functional promoter classes and overlapping promoter codes are present in protochordates like in vertebrates, but show extraordinary lineage-specific innovations. Furthermore, we uncover a genome-wide, developmental stage-specific shift in the mode of TSS selection. Our results provide a rich resource for the study of promoter structure and evolution in Metazoa.}, } @article {pmid29482521, year = {2018}, author = {Wallis, CV and Lowden, P and Marshall-Jones, ZV and Hilton, AC}, title = {Distinct fermentation and antibiotic sensitivity profiles exist in salmonellae of canine and human origin.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {15}, pmid = {29482521}, issn = {1471-2180}, support = {BB/G530192/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Salmonella enterica is a recognised cause of diarrhoea in dogs and humans, yet the potential for transfer of salmonellosis between dogs and their owners is unclear, with reported evidence both for and against Salmonella as a zoonotic pathogen. A collection of 174 S. enterica isolates from clinical infections in humans and dogs were analysed for serotype distribution, carbon source utilisation, chemical and antimicrobial sensitivity profiles. The aim of the study was to understand the degree of conservation in phenotypic characteristics of isolates across host species.

RESULTS: Serovar distribution across human and canine isolates demonstrated nine serovars common to both host species, 24 serovars present in only the canine collection and 39 solely represented within the human collection. Significant differences in carbon source utilisation profiles and ampicillin, amoxicillin and chloramphenicol sensitivity profiles were detected in isolates of human and canine origin. Differences between the human and canine Salmonella collections were suggestive of evolutionary separation, with canine isolates better able to utilise several simple sugars than their human counterparts. Generally higher minimum inhibitory concentrations of three broad-spectrum antimicrobials, commonly used in veterinary medicine, were also observed in canine S. enterica isolates.

CONCLUSIONS: Differential carbon source utilisation and antimicrobial sensitivity profiles in pathogenic Salmonella isolated from humans and dogs are suggestive of distinct reservoirs of infection for these hosts. Although these findings do not preclude zoonotic or anthroponotic potential in salmonellae, the separation of carbon utilisation and antibiotic profiles with isolate source is indicative that infectious isolates are not part of a common reservoir shared frequently between these host species.}, } @article {pmid29482515, year = {2018}, author = {Domínguez, C and Heras, J and Mata, E and Pascual, V}, title = {DecoFungi: a web application for automatic characterisation of dye decolorisation in fungal strains.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {66}, pmid = {29482515}, issn = {1471-2105}, support = {MTM2014-54151-P//Ministerio de Economía y Competitividad/International ; MTM2017-88804-P//Ministerio de Economía y Competitividad/International ; 2017-I-IDD-00018//Agencia de Desarrollo Económico de La Rioja/International ; }, mesh = {Coloring Agents/*chemistry ; Fungi/*metabolism ; *Internet ; Models, Theoretical ; *Software ; User-Computer Interface ; }, abstract = {BACKGROUND: Fungi have diverse biotechnological applications in, among others, agriculture, bioenergy generation, or remediation of polluted soil and water. In this context, culture media based on color change in response to degradation of dyes are particularly relevant; but measuring dye decolorisation of fungal strains mainly relies on a visual and semiquantitative classification of color intensity changes. Such a classification is a subjective, time-consuming and difficult to reproduce process.

RESULTS: DecoFungi is the first, at least up to the best of our knowledge, application to automatically characterise dye decolorisation level of fungal strains from images of inoculated plates. In order to deal with this task, DecoFungi employs a deep-learning model, accessible through a user-friendly web interface, with an accuracy of 96.5%.

CONCLUSIONS: DecoFungi is an easy to use system for characterising dye decolorisation level of fungal strains from images of inoculated plates.}, } @article {pmid29482512, year = {2018}, author = {Oppegaard, O and Mylvaganam, H and Skrede, S and Kittang, BR}, title = {Exploring the arthritogenicity of Streptococcus dysgalactiae subspecies equisimilis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {17}, pmid = {29482512}, issn = {1471-2180}, abstract = {BACKGROUND: During the past decades, Streptococcus dysgalactiae subspecies equisimilis (SDSE) has been increasingly recognized as an important human pathogen. Osteoarticular infections is one of the predominant disease manifestations of SDSE, but the pathogenetic rationale for its arthritogenicity has yet to be unravelled. We aimed to explore if the rising incidence of osteoarticular infections caused by this pathogen in our region emanated from clonal expansion of strains with enhanced tropism for bone and joint tissue components or orthopaedic implants.

RESULTS: Twenty-nine SDSE-isolates associated with osteoarticular infections were retrospectively identified. Their genomic content and affinity for fibronectin, collagen and stainless steel were compared to 24 temporally and geographically matched SDSE blood culture isolates obtained from patients without bone or joint infections. Despite a thorough genetic and phenotypic dissection, neither the presence or absence of any single gene, nor the binding abilities of the SDSE isolates, were predictive of clinical entity. SNP analysis revealed a heterogenous population, and a correlation between phylogenetic relationships and disease manifestation was not evident. However, we identified a strong concordance between phenotypic binding abilities and genetic variations in the pilus-region, also denoted as the FCT-region (Fibronectin binding, Collagen binding and T-antigen). This observation could be related to the ample and varied repertoire of putative adhesins residing within this region, including proteins predicted to adhere to fibronectin and collagen, as well as fibrinogen.

CONCLUSIONS: SDSE strains associated with osteoarticular infections do not emanate from subpopulation characterized by distinct genetic or phenotypic traits. The genetic architecture of the pilus region was predictive of the adhesive properties of the SDSE-isolates, but its role in tissue tropism needs further investigation. To the best of our knowledge, this is the first comprehensive characterization of the genetic landscape of the SDSE pilus region.}, } @article {pmid29482506, year = {2018}, author = {Garrido-Martín, D and Pazos, F}, title = {Effect of the sequence data deluge on the performance of methods for detecting protein functional residues.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {67}, pmid = {29482506}, issn = {1471-2105}, support = {SAF2016-78041-C2-2-R//Spanish Ministry for Economy and Competitiveness/International ; }, mesh = {Algorithms ; Amino Acid Sequence ; Amino Acids/*chemistry ; Binding Sites ; Conserved Sequence ; Molecular Sequence Annotation ; Proteins/*chemistry ; Sequence Alignment ; Sequence Analysis, Protein/*methods ; Time Factors ; }, abstract = {BACKGROUND: The exponential accumulation of new sequences in public databases is expected to improve the performance of all the approaches for predicting protein structural and functional features. Nevertheless, this was never assessed or quantified for some widely used methodologies, such as those aimed at detecting functional sites and functional subfamilies in protein multiple sequence alignments. Using raw protein sequences as only input, these approaches can detect fully conserved positions, as well as those with a family-dependent conservation pattern. Both types of residues are routinely used as predictors of functional sites and, consequently, understanding how the sequence content of the databases affects them is relevant and timely.

RESULTS: In this work we evaluate how the growth and change with time in the content of sequence databases affect five sequence-based approaches for detecting functional sites and subfamilies. We do that by recreating historical versions of the multiple sequence alignments that would have been obtained in the past based on the database contents at different time points, covering a period of 20 years. Applying the methods to these historical alignments allows quantifying the temporal variation in their performance. Our results show that the number of families to which these methods can be applied sharply increases with time, while their ability to detect potentially functional residues remains almost constant.

CONCLUSIONS: These results are informative for the methods' developers and final users, and may have implications in the design of new sequencing initiatives.}, } @article {pmid29482504, year = {2018}, author = {Xu, W and Pan, Y and Xu, Q and Wu, Y and Pan, J and Hou, J and Lin, L and Tang, X and Li, C and Liu, J and Zhang, D}, title = {Porphyromonas gingivalis ATCC 33277 promotes intercellular adhesion molecule-1 expression in endothelial cells and monocyte-endothelial cell adhesion through macrophage migration inhibitory factor.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {16}, pmid = {29482504}, issn = {1471-2180}, abstract = {BACKGROUND: Porphyromonas gingivalis (P. gingivalis), one of the main pathogenic bacteria involved in periodontitis, induces the expression of intercellular adhesion molecule - 1 (ICAM-1) and monocyte-endothelial cell adhesion. This effect plays a pivotal role in atherosclerosis development. Macrophage migration inhibitory factor (MIF) is a multifunctional cytokine and critically affects atherosclerosis pathogenesis. In this study, we tested the involvement of MIF in the P. gingivalis ATCC 33277-enhanced adhesive properties of endothelial cells.

RESULTS: Endothelial MIF expression was enhanced by P. gingivalis ATCC 33277 infection. The MIF inhibitor ISO-1 inhibited ICAM-1 production in endothelial cells, and monocyte-endothelial cell adhesion was induced by P. gingivalis ATCC 33277 infection. However, the addition of exogenous human recombinant MIF to P. gingivalis ATCC 33277-infected endothelial cells facilitated monocyte recruitment by promoting ICAM-1 expression in endothelial cells.

CONCLUSIONS: These experiments revealed that MIF in endothelial cells participates in the pro-atherosclerotic lesion formation caused by P. gingivalis ATCC 33277 infection. Our novel findings identify a more detailed pathological role of P. gingivalis ATCC 33277 in atherosclerosis.}, } @article {pmid29482499, year = {2018}, author = {Al Suwayyid, BA and Coombs, GW and Speers, DJ and Pearson, J and Wise, MJ and Kahler, CM}, title = {Genomic epidemiology and population structure of Neisseria gonorrhoeae from remote highly endemic Western Australian populations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {165}, pmid = {29482499}, issn = {1471-2164}, support = {APP1078642//National Health and Medical Research Council/International ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Cluster Analysis ; DNA, Bacterial ; *Drug Resistance, Bacterial ; Endemic Diseases ; Genomics ; Gonorrhea/epidemiology/genetics/*microbiology ; Humans ; Molecular Epidemiology/*methods ; Multilocus Sequence Typing/methods ; Neisseria gonorrhoeae/*genetics/*isolation & purification ; Phylogeny ; Western Australia/epidemiology ; Whole Genome Sequencing/methods ; }, abstract = {BACKGROUND: Neisseria gonorrhoeae causes gonorrhoea, the second most commonly notified sexually transmitted infection in Australia. One of the highest notification rates of gonorrhoea is found in the remote regions of Western Australia (WA). Unlike isolates from the major Australian population centres, the remote community isolates have low rates of antimicrobial resistance (AMR). Population structure and whole-genome comparison of 59 isolates from the Western Australian N. gonorrhoeae collection were used to investigate relatedness of isolates cultured in the metropolitan and remote areas. Core genome phylogeny, multilocus sequencing typing (MLST), N. gonorrhoeae multi-antigen sequence typing (NG-MAST) and N. gonorrhoeae sequence typing for antimicrobial resistance (NG-STAR) in addition to hierarchical clustering of sequences were used to characterize the isolates.

RESULTS: Population structure analysis of the 59 isolates together with 72 isolates from an international collection, revealed six population groups suggesting that N. gonorrhoeae is a weakly clonal species. Two distinct population groups, Aus1 and Aus2, represented 63% of WA isolates and were mostly composed of the remote community isolates that carried no chromosomal AMR genotypes. In contrast, the Western Australian metropolitan isolates were frequently multi-drug resistant and belonged to population groups found in the international database, suggesting international transmission of the isolates.

CONCLUSIONS: Our study suggests that the population structure of N. gonorrhoeae is distinct between the communities in remote and metropolitan WA. Given the high rate of AMR in metropolitan regions, ongoing surveillance is essential to ensure the enduring efficacy of the empiric gonorrhoea treatment in remote WA.}, } @article {pmid29482496, year = {2018}, author = {Yi, F and Yang, L and Wang, S and Guo, L and Huang, C and Xie, Y and Xiao, G}, title = {Microvessel prediction in H&E Stained Pathology Images using fully convolutional neural networks.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {64}, pmid = {29482496}, issn = {1471-2105}, support = {5P50CA070907/CA/NCI NIH HHS/United States ; RP120732//Cancer Prevention and Research Institute of Texas/International ; 1R01GM115473/GM/NIGMS NIH HHS/United States ; P50 CA070907/CA/NCI NIH HHS/United States ; 1R01CA172211/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; Humans ; *Image Processing, Computer-Assisted ; Microvessels/*pathology ; Neoplasms/pathology ; *Neural Networks (Computer) ; Survival Analysis ; Time Factors ; }, abstract = {BACKGROUND: Pathological angiogenesis has been identified in many malignancies as a potential prognostic factor and target for therapy. In most cases, angiogenic analysis is based on the measurement of microvessel density (MVD) detected by immunostaining of CD31 or CD34. However, most retrievable public data is generally composed of Hematoxylin and Eosin (H&E)-stained pathology images, for which is difficult to get the corresponding immunohistochemistry images. The role of microvessels in H&E stained images has not been widely studied due to their complexity and heterogeneity. Furthermore, identifying microvessels manually for study is a labor-intensive task for pathologists, with high inter- and intra-observer variation. Therefore, it is important to develop automated microvessel-detection algorithms in H&E stained pathology images for clinical association analysis.

RESULTS: In this paper, we propose a microvessel prediction method using fully convolutional neural networks. The feasibility of our proposed algorithm is demonstrated through experimental results on H&E stained images. Furthermore, the identified microvessel features were significantly associated with the patient clinical outcomes.

CONCLUSIONS: This is the first study to develop an algorithm for automated microvessel detection in H&E stained pathology images.}, } @article {pmid29482494, year = {2018}, author = {Liku, ME and Legere, EA and Moses, AM}, title = {NoLogo: a new statistical model highlights the diversity and suggests new classes of Crm1-dependent nuclear export signals.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {65}, pmid = {29482494}, issn = {1471-2105}, mesh = {Amino Acid Sequence ; Cluster Analysis ; Humans ; Hydrophobic and Hydrophilic Interactions ; Karyopherins/chemistry/*metabolism ; Markov Chains ; *Models, Statistical ; *Nuclear Export Signals ; Position-Specific Scoring Matrices ; Probability ; Receptors, Cytoplasmic and Nuclear/chemistry/*metabolism ; Saccharomyces cerevisiae/metabolism ; *Software ; }, abstract = {BACKGROUND: Crm1-dependent Nuclear Export Signals (NESs) are clusters of alternating hydrophobic and non-hydrophobic amino acid residues between 10 to 15 amino acids in length. NESs were largely thought to follow simple consensus patterns, based on which they were categorized into 6-10 classes. However, newly discovered NESs often deviate from the established consensus patterns. Thus, identifying NESs within protein sequences remains a bioinformatics challenge.

RESULTS: We describe a probabilistic representation of NESs using a new generative model we call NoLogo that can account for a large diversity of NESs. Using this model to predict NESs, we demonstrate improved performance over PSSM and GLAM2 models, but do not achieve the performance of the state-of-the-art NES predictor LocNES. Our findings illustrate that over 30% of NESs are best described by novel NES classes rather than the 6-10 classes proposed by current/existing models. Finally, many NESs have additional hydrophobic residues either upstream or downstream of the canonical four residues, suggesting possible functionality.

CONCLUSION: Applying the NoLogo model highlights the observation that NESs are more diverse than previously appreciated. Our work questions the practice of assigning each NES to one of several predefined NES classes. Finally, our analysis suggests a novel and testable biophysical perspective on interaction between Crm1 receptor and Crm1-dependent NESs.}, } @article {pmid29482193, year = {2018}, author = {Bergemann, M and Sesar, B and Cohen, JG and Serenelli, AM and Sheffield, A and Li, TS and Casagrande, L and Johnston, KV and Laporte, CFP and Price-Whelan, AM and Schönrich, R and Gould, A}, title = {Two chemically similar stellar overdensities on opposite sides of the plane of the Galactic disk.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {334-337}, pmid = {29482193}, issn = {1476-4687}, abstract = {Our Galaxy is thought to have an active evolutionary history, dominated over the past ten billion years or so by star formation, the accretion of cold gas and, in particular, the merging of clumps of baryonic and dark matter. The stellar halo-the faint, roughly spherical component of the Galaxy-reveals rich 'fossil' evidence of these interactions, in the form of stellar streams, substructures and chemically distinct stellar components. The effects of interactions with dwarf galaxies on the content and morphology of the Galactic disk are still being explored. Recent studies have identified kinematically distinct stellar substructures and moving groups of stars in our Galaxy, which may have extragalactic origins. There is also mounting evidence that stellar overdensities (regions with greater-than-average stellar density) at the interface between the outer disk and the halo could have been caused by the interaction of a dwarf galaxy with the disk. Here we report a spectroscopic analysis of 14 stars from two stellar overdensities, each lying about five kiloparsecs above or below the Galactic plane-locations suggestive of an association with the stellar halo. We find that the chemical compositions of these two groups of stars are almost identical, both within and between these overdensities, and closely match the abundance patterns of stars in the Galactic disk. We conclude that these stars came from the disk, and that the overdensities that they are part of were created by tidal interactions of the disk with passing or merging dwarf galaxies.}, } @article {pmid29482115, year = {2018}, author = {Evans, JC and Mizrahi, V}, title = {Priming the tuberculosis drug pipeline: new antimycobacterial targets and agents.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {39-46}, doi = {10.1016/j.mib.2018.02.006}, pmid = {29482115}, issn = {1879-0364}, abstract = {Claiming close to two million lives each year, tuberculosis is now the leading cause of death from an infectious disease. The rise in number of Mycobacterium tuberculosis (Mtb) strains resistant to existing TB drugs has underscored the urgent need to develop new antimycobacterials with novel mechanisms of action. To meet this need, a drug pipeline has been established that is populated with new and repurposed drugs. Recent advances in identifying molecules with inhibitory activity against Mtb under conditions modelled on those encountered during infection, and in elucidating their mechanisms of action, have primed the pipeline with promising drug/target couples, hit compounds and new targets. In this review, we highlight recent advances and emerging areas of opportunity in this field.}, } @article {pmid29481949, year = {2018}, author = {Píchová, K and Pažoutová, S and Kostovčík, M and Chudíčková, M and Stodůlková, E and Novák, P and Flieger, M and van der Linde, E and Kolařík, M}, title = {Evolutionary history of ergot with a new infrageneric classification (Hypocreales: Clavicipitaceae: Claviceps).}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {73-87}, doi = {10.1016/j.ympev.2018.02.013}, pmid = {29481949}, issn = {1095-9513}, mesh = {Bayes Theorem ; Claviceps/*classification ; Ergot Alkaloids/biosynthesis/chemistry ; Genetic Loci ; Geography ; Host Specificity ; *Phylogeny ; Secondary Metabolism ; South America ; Time Factors ; }, abstract = {The ergot, genus Claviceps, comprises approximately 60 species of specialised ovarial grass parasites famous for the production of food toxins and pharmaceutics. Although the ergot has been known for centuries, its evolution have not been resolved yet. Our approach combining multilocus phylogeny, molecular dating and the study of ecological, morphological and metabolic features shows that Claviceps originated in South America in the Palaeocene on a common ancestor of BEP (subfamilies Bambusoideae, Ehrhartoideae, Pooideae) and PACMAD (subfamilies Panicoideae, Aristidoideae, Chloridoideae, Micrairoideae, Arundinoideae, Danthonioideae) grasses. Four clades described here as sections diverged during the Paleocene and Eocene. Since Claviceps are parasitic fungi with a close relationship with their host plants, their evolution is influenced by interactions with the new hosts, either by the spread to a new continent or the radiation of the host plants. Three of the sections possess very narrow host ranges and biogeographical distributions and have relatively low toxicity. On the contrary, the section Claviceps, comprising the rye ergot, C. purpurea, is unique in all aspects. Fungi in this section of North American origin have spread all over the world and infect grasses in all subfamilies as well as sedges, and it is the only section synthesising toxic ergopeptines and secalonic acids. The evolutionary success of the Claviceps section members can be explained by high toxin presence, serving as feeding deterrents and playing a role in their protective mutualism with host plants. Closely related taxa Neoclaviceps monostipa and Cepsiclava phalaridis were combined into the genus Aciculosporium.}, } @article {pmid29481638, year = {2018}, author = {Luhtanen, AM and Eronen-Rasimus, E and Oksanen, HM and Tison, JL and Delille, B and Dieckmann, GS and Rintala, JM and Bamford, DH}, title = {The first known virus isolates from Antarctic sea ice have complex infection patterns.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy028}, pmid = {29481638}, issn = {1574-6941}, abstract = {Viruses are recognized as important actors in ocean ecology and biogeochemical cycles, but many details are not yet understood. We participated in a winter expedition to the Weddell Sea, Antarctica, to isolate viruses and to measure virus-like particle abundance (flow cytometry) in sea ice. We isolated 59 bacterial strains and the first four Antarctic sea-ice viruses known (PANV1, PANV2, OANV1 and OANV2), which grow in bacterial hosts belonging to the typical sea-ice genera Paraglaciecola and Octadecabacter. The viruses were specific for bacteria at the strain level, although OANV1 was able to infect strains from two different classes. Both PANV1 and PANV2 infected 11/15 isolated Paraglaciecola strains that had almost identical 16S rRNA gene sequences, but the plating efficiencies differed among the strains, whereas OANV1 infected 3/7 Octadecabacter and 1/15 Paraglaciecola strains and OANV2 1/7 Octadecabacter strains. All the phages were cold-active and able to infect their original host at 0°C and 4°C, but not at higher temperatures. The results showed that virus-host interactions can be very complex and that the viral community can also be dynamic in the winter-sea ice.}, } @article {pmid29481623, year = {2018}, author = {Šantl-Temkiv, T and Gosewinkel, U and Starnawski, P and Lever, M and Finster, K}, title = {Aeolian dispersal of bacteria in southwest Greenland: their sources, abundance, diversity and physiological states.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy031}, pmid = {29481623}, issn = {1574-6941}, abstract = {The Arctic is undergoing dramatic climatic changes that cause profound transformations in its terrestrial ecosystems and consequently in the microbial communities that inhabit them. The assembly of these communities is affected by aeolian deposition. However, the abundance, diversity, sources and activity of airborne microorganisms in the Arctic are poorly understood. We studied bacteria in the atmosphere over southwest Greenland and found that the diversity of bacterial communities correlated positively with air temperature and negatively with relative humidity. The communities consisted of 1.3×103 ± 1.0×103 cells m-3, which were aerosolized from local terrestrial environments or transported from marine, glaciated and terrestrial surfaces over long distances. On average, airborne bacterial cells displayed a high activity potential, reflected in the high 16S rRNA copy number (590 ± 300 rRNA cell-1), that correlated positively with water vapor pressure. We observed that bacterial clades differed in their activity potential. For instance, a high activity potential was seen for Rubrobacteridae and Clostridiales, while a low activity potential was observed for Proteobacteria. Of those bacterial families that harbor ice-nucleation active species, which are known to facilitate freezing and may thus be involved in cloud and rain formation, cells with a high activity potential were rare in air, but were enriched in rain.}, } @article {pmid29480794, year = {2018}, author = {Kim, HC and Kim, YO and Park, S and Nam, BH and Kim, DG and Park, JM and Yoon, JH}, title = {Vitellibacter todarodis sp. nov., isolated from intestinal tract of a squid (Todarodes pacificus).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1233-1237}, doi = {10.1099/ijsem.0.002655}, pmid = {29480794}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Decapodiformes/*microbiology ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Intestines/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-motile, aerobic and rod-shaped or ovoid bacterial strain, designated MYP2-2T, was isolated from the intestinal tract of a squid (Todarodes pacificus) collected from the East Sea, South Korea, and subjected to a polyphasic taxonomic study. Strain MYP2-2T grew optimally at 30-35 °C and in the presence of 2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain MYP2-2T belonged to the genus Vitellibacter. Strain MYP2-2T exhibited 16S rRNA gene sequence similarities of 95.4-96.6 % to the type strains of Vitellibacter species and of less than 94.5 % to the type strains of other recognized species examined. Strain MYP2-2T contained menaquinone MK-6 as the predominant respiratory quinone and iso-C15 : 0 and iso-C17 : 0 3-OH as the major fatty acids. The major polar lipids detected in strain MYP2-2T were phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of strain MYP2-2T was 41.6 mol%. Differential phenotypic properties, together with its phylogenetic distinctiveness, revealed that strain MYP2-2T is separated from recognized species of the genus Vitellibacter. On the basis of the data presented, strain MYP2-2T is considered to represent a novel species of the genus Vitellibacter, for which the name Vitellibacter todarodis sp. nov. is proposed. The type strain is MYP2-2T (=KCTC 62141T=NBRC 113025T).}, } @article {pmid29480418, year = {2018}, author = {Oh, M and Kim, JH and Yoon, JH and Schumann, P and Kim, W}, title = {Cellulosimicrobium arenosum sp. nov., Isolated from Marine Sediment Sand.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {901-906}, pmid = {29480418}, issn = {1432-0991}, mesh = {Actinomycetales/classification/genetics/*isolation & purification/metabolism ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry/metabolism ; Geologic Sediments/*microbiology ; Peptidoglycan/chemistry/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {A Gram-stain-positive, non-spore-forming, yellow pigmented, non-motile, aerobic, short rod-shaped bacterial strain, designated CAU 1455T, was isolated from marine sediment sand. Strain CAU 1455T grew optimally at 30 °C and at pH 7.5 in the presence of 1% (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CAU 1455T was affiliated to the genus Cellulosimicrobium and was most closely related to Cellulosimicrobium terreum DS-61T (similarity 97.9%). The strain possessed MK-9 (H4) as the predominant menaquinone and anteiso-C15:0 as the major cellular fatty acids. Peptidoglycan type was A4a (L-Lys-D-Glu2). The DNA G+C content was 74.3 mol% and the level of DNA-DNA relatedness between CAU 1455T and C. terreum DS-61T was 27.8%. Based on phenotypic, chemotaxonomic, and genetic data, strain CAU 1455T represents a novel species of the genus Cellulosimicrobium, for which the name Cellulosimicrobium arenosum sp. nov. is proposed. The type strain is CAU 1455T (= KCTC 49039T = NBRC 113062T).}, } @article {pmid29480323, year = {2018}, author = {Vaidya, S and Dev, K and Sourirajan, A}, title = {Distinct Osmoadaptation Strategies in the Strict Halophilic and Halotolerant Bacteria Isolated from Lunsu Salt Water Body of North West Himalayas.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {888-895}, pmid = {29480323}, issn = {1432-0991}, mesh = {Adaptation, Physiological ; Bacteria/classification/genetics/*isolation & purification/*metabolism ; India ; Osmosis ; *Salt Tolerance ; Sodium Chloride/analysis/metabolism ; Water/*analysis ; *Water Microbiology ; }, abstract = {Two strict halophilic bacterial strains, Halobacillus trueperi SS1, and Halobacillus trueperi SS3, and three halotolerant bacterial strains, Shewanella algae SS2, Halomonas venusta SS5, and Marinomonas sp. SS8 of Lunsu salt water body, Himachal Pradesh, India, were selected to study the mechanism of salt tolerance and the role of osmolytes therein. A combination of flame photometry, chromatographic and colorimetric assays was used to study the mechanism of salt tolerance in the selected strict halophilic and halotolerant bacterial strains. The strict halophiles and, one of the halotolerants, Marinomonas sp. SS8 were found to utilize both "salt-in strategy" and "accumulation of compatible solutes strategy" for osmoregulation in hypersaline conditions. On the contrary, the remaining two halotolerants used "accumulation of compatible solutes strategy" under saline stress and not the "salt-in strategy". The present study suggests towards distinct mechanisms of salt tolerance in the two classes, wherein strict halophiles accumulate compatible solutes as well as adopt salt-in strategy, while the halotolerant bacteria accumulate a range of compatible solutes, except Marinomonas sp. SS8, which utilizes both the strategies to combat salt stress.}, } @article {pmid29479084, year = {2018}, author = {Ge, Y and Fuchs, E}, title = {Stretching the limits: from homeostasis to stem cell plasticity in wound healing and cancer.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {311-325}, pmid = {29479084}, issn = {1471-0064}, support = {R01 AR050452/AR/NIAMS NIH HHS/United States ; }, abstract = {Stem cells (SCs) govern tissue homeostasis and wound repair. They reside within niches, the special microenvironments within tissues that control SC lineage outputs. Upon injury or stress, new signals emanating from damaged tissue can divert nearby cells into adopting behaviours that are not part of their homeostatic repertoire. This behaviour, known as SC plasticity, typically resolves as wounds heal. However, in cancer, it can endure. Recent studies have yielded insights into the orchestrators of maintenance and lineage commitment for SCs belonging to three mammalian tissues: the haematopoietic system, the skin epithelium and the intestinal epithelium. We delineate the multifactorial determinants and general principles underlying the remarkable facets of SC plasticity, which lend promise for regenerative medicine and cancer therapeutics.}, } @article {pmid29479083, year = {2018}, author = {Zlotorynski, E}, title = {Gene expression: Developmental enhancers in action.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {187}, pmid = {29479083}, issn = {1471-0064}, } @article {pmid29479082, year = {2018}, author = {Karczewski, KJ and Snyder, MP}, title = {Integrative omics for health and disease.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {299-310}, pmid = {29479082}, issn = {1471-0064}, support = {F32 GM115208/GM/NIGMS NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 HL122887/HL/NHLBI NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, abstract = {Advances in omics technologies - such as genomics, transcriptomics, proteomics and metabolomics - have begun to enable personalized medicine at an extraordinarily detailed molecular level. Individually, these technologies have contributed medical advances that have begun to enter clinical practice. However, each technology individually cannot capture the entire biological complexity of most human diseases. Integration of multiple technologies has emerged as an approach to provide a more comprehensive view of biology and disease. In this Review, we discuss the potential for combining diverse types of data and the utility of this approach in human health and disease. We provide examples of data integration to understand, diagnose and inform treatment of diseases, including rare and common diseases as well as cancer and transplant biology. Finally, we discuss technical and other challenges to clinical implementation of integrative omics.}, } @article {pmid29479077, year = {2018}, author = {Xin, XF and Kvitko, B and He, SY}, title = {Pseudomonas syringae: what it takes to be a pathogen.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {316-328}, pmid = {29479077}, issn = {1740-1534}, support = {R01 GM109928/GM/NIGMS NIH HHS/United States ; }, abstract = {Pseudomonas syringae is one of the best-studied plant pathogens and serves as a model for understanding host-microorganism interactions, bacterial virulence mechanisms and host adaptation of pathogens as well as microbial evolution, ecology and epidemiology. Comparative genomic studies have identified key genomic features that contribute to P. syringae virulence. P. syringae has evolved two main virulence strategies: suppression of host immunity and creation of an aqueous apoplast to form its niche in the phyllosphere. In addition, external environmental conditions such as humidity profoundly influence infection. P. syringae may serve as an excellent model to understand virulence and also of how pathogenic microorganisms integrate environmental conditions and plant microbiota to become ecologically robust and diverse pathogens of the plant kingdom.}, } @article {pmid29479076, year = {2018}, author = {Du Toit, A}, title = {Viral infection: CRISPR-Cas enhances HGT by transduction.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {186}, pmid = {29479076}, issn = {1740-1534}, } @article {pmid29479075, year = {2018}, author = {Du Toit, A}, title = {Antimicrobials: Breaking ground for new antibiotics.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {186}, pmid = {29479075}, issn = {1740-1534}, } @article {pmid29479074, year = {2018}, author = {York, A}, title = {Cellular microbiology: Lysozyme protects bacteria from β-lactams.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {183}, pmid = {29479074}, issn = {1740-1534}, } @article {pmid29479073, year = {2018}, author = {Du Toit, A}, title = {Microbiome: Principles of microbiota engraftment.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {186}, pmid = {29479073}, issn = {1740-1534}, } @article {pmid29479072, year = {2018}, author = {Fisher, CR and Streicker, DG and Schnell, MJ}, title = {The spread and evolution of rabies virus: conquering new frontiers.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {241-255}, pmid = {29479072}, issn = {1740-1534}, abstract = {Rabies is a lethal zoonotic disease that is caused by lyssaviruses, most often rabies virus. Despite control efforts, sporadic outbreaks in wildlife populations are largely unpredictable, underscoring our incomplete knowledge of what governs viral transmission and spread in reservoir hosts. Furthermore, the evolutionary history of rabies virus and related lyssaviruses remains largely unclear. Robust surveillance efforts combined with diagnostics and disease modelling are now providing insights into the epidemiology and evolution of rabies virus. The immune status of the host, the nature of exposure and strain differences all clearly influence infection and transmission dynamics. In this Review, we focus on rabies virus infections in the wildlife and synthesize current knowledge in the rapidly advancing fields of rabies virus epidemiology and evolution, and advocate for multidisciplinary approaches to advance our understanding of this disease.}, } @article {pmid29478337, year = {2018}, author = {Pham, MN and Barbaro, N and Holub, AM and Holden, CJ and Mogilski, JK and Lopes, GS and Nicolas, SCA and Sela, Y and Shackelford, TK and Zeigler-Hill, V and Welling, LLM}, title = {Do Men Produce Higher Quality Ejaculates When Primed With Thoughts of Partner Infidelity?.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704918757551}, doi = {10.1177/1474704918757551}, pmid = {29478337}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Ejaculation/*physiology ; Humans ; Male ; Sexual Behavior/*physiology/psychology ; Sexual Partners/*psychology ; Sperm Count ; Young Adult ; }, abstract = {Sperm competition theory can be used to generate the hypothesis that men alter the quality of their ejaculates as a function of sperm competition risk. Using a repeated measures experimental design, we investigated whether men produce a higher quality ejaculate when primed with cues to sperm competition (i.e., imagined partner infidelity) relative to a control prime. Men (n = 45) submitted two masturbatory ejaculates-one ejaculate sample for each condition (i.e., sperm competition and control conditions). Ejaculates were assessed on 17 clinical parameters. The results did not support the hypothesis: Men did not produce higher quality ejaculates in the sperm competition condition relative to the control condition. Despite the null results of the current research, there is evidence for psychological and physiological adaptations to sperm competition in humans. We discuss methodological limitations that may have produced the null results and present methodological suggestions for research on human sperm competition.}, } @article {pmid29478241, year = {2018}, author = {Nguyen, NT}, title = {Acinetobacter soli SP2 Capable of High-Efficiency Degradation of Food Emulsifier Polysorbate 80.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {896-900}, pmid = {29478241}, issn = {1432-0991}, mesh = {Acinetobacter/drug effects/genetics/isolation & purification/*metabolism ; Ampicillin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Drug Resistance, Bacterial ; Emulsifying Agents/*metabolism ; Food Additives/*metabolism ; Polysorbates/*metabolism ; }, abstract = {Emulsifiers like polysorbate family, carboxymethyl cellulose are widely used in the preparation of drugs, vaccines, food, cosmetics, and skin care products. In this study, strain SP2 is isolated for the high-efficiency utilization of emulsifier as its sole carbon and energy source. Strain grows on the polysorbate family with generation time ranging from 0.8 to 2.2 h. It is sensitive to ampicillin, gentamicin, imipenem, penicillin, and vancomycin, but resistant to amikacin, cefoxitin, erythromycin, kanamycin, nalidixic acid, and tetracycline. Based on 16S rRNA gene, strain is identified as Acinetobacter soli. Compared to M. pamicella, which is capable of degrading 50% polysorbate 80 within 3 days, isolate PS2 could dispose 51.6% polysorbate 80 within only 8 h. Using cell crude extract from strain SP2, the liberation of free fatty acid in the reaction mixture containing polysorbate 80 suggests that the mechanism for polysorbate utilization belongs to the β-oxidation.}, } @article {pmid29477730, year = {2018}, author = {Pinaud, L and Sansonetti, PJ and Phalipon, A}, title = {Host Cell Targeting by Enteropathogenic Bacteria T3SS Effectors.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {266-283}, doi = {10.1016/j.tim.2018.01.010}, pmid = {29477730}, issn = {1878-4380}, abstract = {Microbial pathogens possess a diversity of weapons that disrupt host homeostasis and immune defenses, thus resulting in the establishment of infection. The best-characterized system mediating bacterial protein delivery into target eukaryotic cells is the type III secretion system (T3SS) expressed by Gram-negative bacteria, including the human enteric pathogens Shigella, Salmonella, Yersinia, and enteropathogenic/enterohemorragic Escherichia coli (EPEC/EHEC). The emerging global view is that these T3SS-bearing pathogens share similarities in their ability to target key cellular pathways such as the cell cytoskeleton, trafficking, cell death/survival, and the NF-κB and MAPK signaling pathways. In particular, multiple host proteins are targeted in a given pathway, and different T3SS effectors from various pathogens share functional similarities.}, } @article {pmid29477583, year = {2018}, author = {Smirnova, GV and Tyulenev, AV and Muzyka, NG and Oktyabrsky, ON}, title = {The sharp phase of respiratory inhibition during amino acid starvation in Escherichia coli is RelA-dependent and associated with regulation of ATP synthase activity.}, journal = {Research in microbiology}, volume = {169}, number = {3}, pages = {157-165}, doi = {10.1016/j.resmic.2018.02.003}, pmid = {29477583}, issn = {1769-7123}, mesh = {Adenosine Triphosphate/metabolism ; Amino Acids/*metabolism ; Cell Respiration ; Enzyme Activation ; Escherichia coli/genetics/*metabolism ; Hydrogen Peroxide/metabolism ; Membrane Potentials ; Oxygen/metabolism ; Potassium/metabolism ; Proton-Translocating ATPases/*metabolism ; Superoxides/metabolism ; Transcription Factor RelA/genetics/*metabolism ; }, abstract = {Amino acid starvation causes an RelA-dependent increase in the regulatory nucleotide (p)ppGpp that leads to pleiotropic changes in Escherichia coli metabolism, but the role of (p)ppGpp in regulation of respiration remains unclear. Here we demonstrate that amino acid starvation is accompanied by sharp RelA-dependent inhibition of respiration. The sharp phase of inhibition is absent in relA mutants, and can be prevented by translation inhibitors chloramphenicol and tetracycline, which abolish accumulation of (p)ppGpp. Single knockouts of any components of the respiratory chain do not affect inhibition of respiration. Studies of dO2 changes in various atp mutants indicate that ATP synthase is probably the primary target of (p)ppGpp-mediated respiratory control. Inhibition of respiration induced by amino acid starvation is followed by transient perturbations in the membrane potential (Δψ) and K+ fluxes and leads to transient acceleration of superoxide production and H2O2 accumulation in the medium. High levels of H2O2 and superoxide formation and induced activity of antioxidant systems in the atpC mutant indicate the important role of ATP synthase in controlling the production of reactive oxygen species. The new function of (p)ppGpp, discovered here, expands the understanding of its role in metabolic reprogramming during the adaptive response to stresses.}, } @article {pmid29477508, year = {2018}, author = {Storchová, Z}, title = {Sphingolipid Turnover Turns Over the Fate of Aneuploid Cells.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {255-256}, doi = {10.1016/j.tig.2018.02.004}, pmid = {29477508}, issn = {0168-9525}, mesh = {Aneuploidy ; Homeostasis ; Humans ; Neoplasms ; *Serine ; *Sphingolipids ; }, abstract = {Aneuploidy, or unbalanced chromosome number, is a hallmark of cancer. Recently established model systems revealed that aneuploidy affects many aspects of cellular physiology, among them sphingolipid metabolism. The new finding that the proliferation of aneuploid cells depends on sphingolipid homeostasis offers an appealing opportunity for cancer treatment.}, } @article {pmid29477443, year = {2018}, author = {Ingrisch, J and Bahn, M}, title = {Towards a Comparable Quantification of Resilience.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {251-259}, doi = {10.1016/j.tree.2018.01.013}, pmid = {29477443}, issn = {1872-8383}, mesh = {Conservation of Natural Resources/trends ; Ecology/*methods/*trends ; *Ecosystem ; *Models, Biological ; }, abstract = {Resilience is a key concept in ecology and describes the capacity of an ecosystem to maintain its state and recover from disturbances. Numerous metrics have been applied to quantify resilience over a range of ecosystems. However, the way resilience is quantified affects the degree to which different trajectories of ecosystem recovery from disturbance are represented as 'resilient', precluding a comparison of disturbance responses across ecosystems and their properties and functions. To approach a broadly comparable assessment of resilience we suggest using a bivariate framework that jointly considers the disturbance impact and the recovery rate, both normalized to the undisturbed state of a system. We demonstrate the potential of the framework for attribution and integration across the various components underlying resilience.}, } @article {pmid29477383, year = {2018}, author = {Lecaudey, LA and Schliewen, UK and Osinov, AG and Taylor, EB and Bernatchez, L and Weiss, SJ}, title = {Inferring phylogenetic structure, hybridization and divergence times within Salmoninae (Teleostei: Salmonidae) using RAD-sequencing.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {82-99}, doi = {10.1016/j.ympev.2018.02.022}, pmid = {29477383}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Calibration ; Data Analysis ; Fossils ; *Genetic Variation ; *Hybridization, Genetic ; Likelihood Functions ; *Phylogeny ; *Restriction Mapping ; Salmonidae/*classification/*genetics ; Sequence Analysis, DNA/*methods ; Time Factors ; }, abstract = {Phylogenetic studies focusing on Salmonidae have revealed significant obstacles in trying to clarify some interspecific relationships within the Salmoninae subfamily, due to a limited number of markers typed, conflicting phylogenetic signals and ancient hybridization events. To infer reliable phylogenetic relationships, evaluate several putative scenarios of ancient hybridization, and estimate divergence times within Salmoninae, we applied restriction-site associated DNA sequencing (RAD-seq) to 43 samples, including 26 genetic lineages across 21 species, largely representing the subfamily, with an emphasis on the genus Salvelinus. We identified 28,402 loci and 28,363 putatively unlinked SNPs, which were used in downstream analyses. Using an iterative k-means partitioned dataset and a Maximum Likelihood approach; we generated a well-supported phylogeny, providing clear answers to several previous phylogenetic uncertainties. We detected several significant introgression signals, presumably ancient, in the genus Salvelinus. The most recent common ancestor of Salmonidae dates back to approximately 58.9MY ago (50.8-64 MY) and the crown age of Salmoninae was estimated to be 37.7 MY (35.2-40.8 MY) using a Bayesian molecular dating analysis with a relaxed molecular clock. The divergence among genera of the subfamily occurred between the late Eocene and middle of the Miocene (≈38-11 MY) such as the divergence between the genus Oncorhynchus and Salvelinus, which we estimated to 21.2 MY ago (95% HPD: 19.8-23.0 MY), while species diversification took place mainly during the Neogene (≈22-1.5 MY), with more than half of these events occurring in the last 10 MY.}, } @article {pmid29477341, year = {2018}, author = {Bouffard, S and Dambroise, E and Brombin, A and Lempereur, S and Hatin, I and Simion, M and Corre, R and Bourrat, F and Joly, JS and Jamen, F}, title = {Fibrillarin is essential for S-phase progression and neuronal differentiation in zebrafish dorsal midbrain and retina.}, journal = {Developmental biology}, volume = {437}, number = {1}, pages = {1-16}, doi = {10.1016/j.ydbio.2018.02.006}, pmid = {29477341}, issn = {1095-564X}, mesh = {Animals ; Apoptosis ; Cell Differentiation/*genetics ; Chromosomal Proteins, Non-Histone/*metabolism ; Larva/metabolism ; Mesencephalon/*embryology/metabolism ; Morphogenesis/genetics ; Neurogenesis/genetics ; RNA, Ribosomal/metabolism ; Retina/*embryology/metabolism ; S Phase/*genetics ; Zebrafish/embryology ; }, abstract = {Fibrillarin (Fbl) is a highly conserved protein that plays an essential role in ribosome biogenesis and more particularly in the methylation of ribosomal RNAs and rDNA histones. In cellular models, FBL was shown to play an important role in tumorigenesis and stem cell differentiation. We used the zebrafish as an in vivo model to study Fbl function during embryonic development. We show here that the optic tectum and the eye are severely affected by Fbl depletion whereas ventral regions of the brain are less impacted. The morphogenesis defects are associated with impaired neural differentiation and massive apoptosis. Polysome gradient experiments show that fbl mutant larvae display defects in ribosome biogenesis and activity. Strikingly, flow cytometry analyses revealed different S-phase profiles between wild-type and mutant cells, suggesting a defect in S-phase progression.}, } @article {pmid29477340, year = {2018}, author = {Krauchunas, AR and Mendez, E and Ni, JZ and Druzhinina, M and Mulia, A and Parry, J and Gu, SG and Stanfield, GM and Singson, A}, title = {spe-43 is required for sperm activation in C. elegans.}, journal = {Developmental biology}, volume = {436}, number = {2}, pages = {75-83}, pmid = {29477340}, issn = {1095-564X}, support = {R25 GM058389/GM/NIGMS NIH HHS/United States ; K12 GM093854/GM/NIGMS NIH HHS/United States ; R01 HD054681/HD/NICHD NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R25 GM055145/GM/NIGMS NIH HHS/United States ; R01 GM087705/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/*genetics/metabolism ; Fertility/genetics ; Male ; Mutation ; Phenotype ; Polymorphism, Single Nucleotide ; Reverse Transcriptase Polymerase Chain Reaction ; Spermatogenesis/*genetics/physiology ; Spermatozoa/*metabolism/physiology ; Whole Genome Sequencing ; }, abstract = {Successful fertilization requires that sperm are activated prior to contacting an oocyte. In C. elegans, this activation process, called spermiogenesis, transforms round immobile spermatids into motile, fertilization-competent spermatozoa. We describe the phenotypic and genetic characterization of spe-43, a new component of the spe-8 pathway, which is required for spermiogenesis in hermaphrodites; spe-43 hermaphrodites are self-sterile, while spe-43 males show wild-type fertility. When exposed to Pronase to activate sperm in vitro, spe-43 spermatids form long rigid spikes radiating outward from the cell periphery instead of forming a motile pseudopod, indicating that spermiogenesis initiates but is not completed. Using a combination of recombinant and deletion mapping and whole genome sequencing, we identified F09E8.1 as spe-43. SPE-43 is predicted to exist in two isoforms; one isoform appears to be a single-pass transmembrane protein while the other is predicted to be a secreted protein. SPE-43 can bind to other known sperm proteins, including SPE-4 and SPE-29, which are known to impact spermiogenesis. In summary, we have identified a membrane protein that is present in C. elegans sperm and is required for sperm activation via the hermaphrodite activation signal.}, } @article {pmid29477339, year = {2018}, author = {Pfeiffer, J and Tarbashevich, K and Bandemer, J and Palm, T and Raz, E}, title = {Rapid progression through the cell cycle ensures efficient migration of primordial germ cells - The role of Hsp90.}, journal = {Developmental biology}, volume = {436}, number = {2}, pages = {84-93}, doi = {10.1016/j.ydbio.2018.02.014}, pmid = {29477339}, issn = {1095-564X}, mesh = {Animals ; Cell Cycle/*genetics ; Cell Division/*genetics/physiology ; Cell Movement/*genetics/physiology ; Germ Cells/cytology/*metabolism/physiology ; HSP90 Heat-Shock Proteins/*metabolism ; In Situ Hybridization ; Zebrafish/genetics ; }, abstract = {Zebrafish primordial germ cells (PGCs) constitute a useful in vivo model to study cell migration and to elucidate the role of specific proteins in this process. Here we report on the role of the heat shock protein Hsp90aa1.2, a protein whose RNA level is elevated in the PGCs during their migration. Reducing Hsp90aa1.2 activity slows down the progression through the cell cycle and leads to defects in the control over the MTOC number in the migrating cells. These defects result in a slower migration rate and compromise the arrival of PGCs at their target, the region where the gonad develops. Our results emphasize the importance of ensuring rapid progression through the cell cycle during single-cell migration and highlight the role of heat shock proteins in the process.}, } @article {pmid29477184, year = {2018}, author = {Cote, S and Kingston, J and Deino, A and Winkler, A and Kityo, R and MacLatchy, L}, title = {Evidence for rapid faunal change in the early Miocene of East Africa based on revised biostratigraphic and radiometric dating of Bukwa, Uganda.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {95-107}, doi = {10.1016/j.jhevol.2017.12.001}, pmid = {29477184}, issn = {1095-8606}, abstract = {Field expeditions to Bukwa in the late 1960s and early 1970s established that the site had a small but diverse early Miocene fauna, including the catarrhine primate Limnopithecus legetet. Initial potassium-argon radiometric dating indicated that Bukwa was 22 Ma, making it the oldest of the East African early Miocene fossil localities known at the time. In contrast, the fauna collected from Bukwa was similar to other fossil localities in the region that were several million years younger. This discrepancy was never resolved, and due to the paucity of primate remains at the site, little subsequent research took place. We have collected new fossils at Bukwa, reanalyzed the existing fossil collections, and provided new radiometric dating. 40Ar/39Ar incremental heating ages on lavas bracketing the site indicate that the Bukwa fossils were deposited ∼19 Ma, roughly 3 Ma younger than the original radiometric age. Our radiometric dating results are corroborated by a thorough reanalysis of the faunal assemblage. Bukwa shares taxa with both stratigraphically older localities (Tinderet, Napak) and with stratigraphically younger localities (Kisingiri, Turkana Basin) perfectly corresponding to our revised radiometric age. This revised age for Bukwa is important because it indicates that significant faunal turnover may have occurred in East Africa between 20 and 19 Ma. Bukwa samples immigrant taxa such as large suids, large ruminants, and ochotonids that are absent from stratigraphically older but well-sampled localities in the region, such as Tinderet (∼20 Ma) and Napak (20 Ma). Further age refinements for Bukwa and the entire East African early Miocene sequence will help to constrain the timing of this faunal turnover event, of particular importance in paleoanthropology since this temporal sequence also provides us with what is currently our best window into the early evolution of cercopithecoid and hominoid primates.}, } @article {pmid29477183, year = {2018}, author = {Yost, CL and Jackson, LJ and Stone, JR and Cohen, AS}, title = {Subdecadal phytolith and charcoal records from Lake Malawi, East Africa imply minimal effects on human evolution from the ∼74 ka Toba supereruption.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {75-94}, doi = {10.1016/j.jhevol.2017.11.005}, pmid = {29477183}, issn = {1095-8606}, abstract = {The temporal proximity of the ∼74 ka Toba supereruption to a putative 100-50 ka human population bottleneck is the basis for the volcanic winter/weak Garden of Eden hypothesis, which states that the eruption caused a 6-year-long global volcanic winter and reduced the effective population of anatomically modern humans (AMH) to fewer than 10,000 individuals. To test this hypothesis, we sampled two cores collected from Lake Malawi with cryptotephra previously fingerprinted to the Toba supereruption. Phytolith and charcoal samples were continuously collected at ∼3-4 mm (∼8-9 yr) intervals above and below the Toba cryptotephra position, with no stratigraphic breaks. For samples synchronous or proximal to the Toba interval, we found no change in low elevation tree cover, or in cool climate C3 and warm season C4 xerophytic and mesophytic grass abundance that is outside of normal variability. A spike in locally derived charcoal and xerophytic C4 grasses immediately after the Toba eruption indicates reduced precipitation and die-off of at least some afromontane vegetation, but does not signal volcanic winter conditions. A review of Toba tuff petrological and melt inclusion studies suggest a Tambora-like 50 to 100 Mt SO2 atmospheric injection. However, most Toba climate models use SO2 values that are one to two orders of magnitude higher, thereby significantly overestimating the amount of cooling. A review of recent genetic studies finds no support for a genetic bottleneck at or near ∼74 ka. Based on these previous studies and our new paleoenvironmental data, we find no support for the Toba catastrophe hypothesis and conclude that the Toba supereruption did not 1) produce a 6-year-long volcanic winter in eastern Africa, 2) cause a genetic bottleneck among African AMH populations, or 3) bring humanity to the brink of extinction.}, } @article {pmid29477182, year = {2018}, author = {Warren, KA and Ritzman, TB and Humphreys, RA and Percival, CJ and Hallgrímsson, B and Ackermann, RR}, title = {Craniomandibular form and body size variation of first generation mouse hybrids: A model for hominin hybridization.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {57-74}, doi = {10.1016/j.jhevol.2017.12.002}, pmid = {29477182}, issn = {1095-8606}, abstract = {Hybridization occurs in a number of mammalian lineages, including among primate taxa. Analyses of ancient genomes have shown that hybridization between our lineage and other archaic hominins in Eurasia occurred numerous times in the past. However, we still have limited empirical data on what a hybrid skeleton looks like, or how to spot patterns of hybridization among fossils for which there are no genetic data. Here we use experimental mouse models to supplement previous studies of primates. We characterize size and shape variation in the cranium and mandible of three wild-derived inbred mouse strains and their first generation (F1) hybrids. The three parent taxa in our analysis represent lineages that diverged over approximately the same period as the human/Neanderthal/Denisovan lineages and their hybrids are variably successful in the wild. Comparisons of body size, as quantified by long bone measurements, are also presented to determine whether the identified phenotypic effects of hybridization are localized to the cranium or represent overall body size changes. The results indicate that hybrid cranial and mandibular sizes, as well as limb length, exceed that of the parent taxa in all cases. All three F1 hybrid crosses display similar patterns of size and form variation. These results are generally consistent with earlier studies on primates and other mammals, suggesting that the effects of hybridization may be similar across very different scenarios of hybridization, including different levels of hybrid fitness. This paper serves to supplement previous studies aimed at identifying F1 hybrids in the fossil record and to introduce further research that will explore hybrid morphologies using mice as a proxy for better understanding hybridization in the hominin fossil record.}, } @article {pmid29477181, year = {2018}, author = {Rouly, OC}, title = {A computer simulation to investigate the association between gene-based gifting and pair-bonding in early hominins.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {43-56}, pmid = {29477181}, issn = {1095-8606}, abstract = {This article describes simulation research based on the Hamiltonian theory of gene-based altruism. It investigates the origin of semipermanent breeding bonds during hominin evolution. The research framework is based on a biologically detailed, ecologically situated, multi-agent microsimulation of emergent sociality. The research question tested is whether semipermanent breeding bonds (an emergent homoplastic social construct) might emerge among primate-like agents as the consequence of a mutation capable of supporting involuntary prosocial behavior. The research protocol compared several, single independent-variable longitudinal studies wherein hundreds of generations of autonomous, initially promiscuous, biologically detailed, hominin-like artificial life software agents were born, allowed to forage, reproduce, and die during experimental intervals lasting several simulated millennia. The temporal setting of the experiment was roughly contemporaneous with, or slightly after the time of, the Pan-Homo split. The simulation investigated what would happen if, within a population, a single gene for prosocial behavior (the independent variable in the experiment) was either switched on or switched-off. The null hypothesis predicted that, if the gene was switched off, then semipermanent breeding bonds (the dependent variable) would nonetheless emerge within the population. The results of the simulation rejected this null hypothesis, by showing that semipermanent breeding bonds would reliably emerge among the experimental populations but not among the control groups. Moreover, it was found that, across all experimental settings having constrained population numbers, the portion of each population having no prosocial trait would die out early, whereas the portion with the prosocial trait would survive. Large control populations had no discernible loss. The results of this research imply that, during the early stages of hominin evolution, there might have been a set of initially gene-based, altruistic excess forage-sharing social traits that contributed to the onset of morphological and additional complex social changes characteristic of this group. This work also demonstrates that modern computational technologies can extend our ability to test 'what if' hypotheses appropriate to the study of early hominin evolution.}, } @article {pmid29477180, year = {2018}, author = {Stanistreet, IG and Stollhofen, H and Njau, JK and Farrugia, P and Pante, MC and Masao, FT and Albert, RM and Bamford, MK}, title = {Lahar inundated, modified, and preserved 1.88 Ma early hominin (OH24 and OH56) Olduvai DK site.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {27-42}, doi = {10.1016/j.jhevol.2017.11.011}, pmid = {29477180}, issn = {1095-8606}, abstract = {Archaeological excavations at the DK site in the eastern Olduvai Basin, Tanzania, age-bracketed between ∼1.88 Ma (Bed I Basalt) and ∼1.85 Ma (Tuff IB), record the oldest lahar inundation, modification, and preservation of a hominin "occupation" site yet identified. Our landscape approach reconstructs environments and processes at high resolution to explain the distribution and final preservation of archaeological materials at the DK site, where an early hominin (likely Homo habilis) assemblage of stone tools and bones, found close to hominin specimens OH24 and OH56, developed on an uneven heterogeneous surface that was rapidly inundated by a lahar and buried to a depth of 0.4-1.2 m (originally ∼1.0-2.4 m pre-compaction). The incoming intermediate to high viscosity mudflow selectively modified the original accumulation of "occupation debris," so that it is no longer confined to the original surface. A dispersive debris "halo" was identified within the lahar deposit: debris is densest immediately above the site, but tails off until not present >150 m laterally. Voorhies indices and metrics derived from limb bones are used to define this dispersive halo spatially and might indicate a possible second assemblage to the east that is now eroded away. Based upon our new data and prior descriptions, two possibilities for the OH24 skull are suggested: it was either entrained by the mudflow from the DK surface and floated due to lower density toward its top, or it was deposited upon the solid top surface after its consolidation. Matrix adhering to material found in association with the parietals indicates that OH56 at least was relocated by the mudflow.}, } @article {pmid29477179, year = {2018}, author = {DeMiguel, D and Rook, L}, title = {Understanding climate's influence on the extinction of Oreopithecus (late Miocene, Tusco-Sardinian paleobioprovince, Italy).}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {14-26}, doi = {10.1016/j.jhevol.2017.11.008}, pmid = {29477179}, issn = {1095-8606}, abstract = {Despite its long history of scientific study, the causes underlying the extinction of the insular hominoid Oreopithecus bambolii are still a matter of ongoing debate. While some authors consider intense tectonism and invading species the cause of its extinction ca. 6.7 Ma, others propose climatic change as the main contributing factor. We rely on long-term patterns of tooth wear and hypsodonty of the Baccinello and Fiume Santo herbivore-faunas to reconstruct changes in habitat prior to, during and after the extinction. While a mosaic of habitats was represented in Baccinello V1 (as shown by a record of browsers, mixed feeders and species engaged in grazing), more closed forests (higher proportion of browsers, shortage of mixed feeders and lack of grazers) characterised Baccinello V2. Finally, there was a partial loss of canopy cover and development of open-patches and low-abrasive grasses in Baccinello V3 (as denoted by new records of taxa involved in grazing)-although still dominated by a forested habitat (since browse was a component in all diets). Our results provide evidence for two perceptible shifts in climate, one between 8.1 and 7.1 Ma and other ca. 6.7 Ma, though this latter was not drastic enough to lead to intensive forest loss, substantially alter the local vegetation or affect Oreopithecus lifestyle-especially if considering the growing evidence of its versatile diet. Although the disappearance of Oreopithecus is complex, our data reject the hypothesis of environmental change as the main factor in the extinction of Oreopithecus and Maremma fauna. When our results are analysed together with other evidence, faunal interaction and predation by invading species from mainland Europe seems to be the most parsimonious explanation for this extinction event. This contrasts with European hominoid extinctions that were associated with major climatic shifts that led to environmental uniformity and restriction of the preferred habitats of Miocene apes.}, } @article {pmid29477178, year = {2018}, author = {Zanolli, C and Pan, L and Dumoncel, J and Kullmer, O and Kundrát, M and Liu, W and Macchiarelli, R and Mancini, L and Schrenk, F and Tuniz, C}, title = {Inner tooth morphology of Homo erectus from Zhoukoudian. New evidence from an old collection housed at Uppsala University, Sweden.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {1-13}, doi = {10.1016/j.jhevol.2017.11.002}, pmid = {29477178}, issn = {1095-8606}, abstract = {Locality 1, in the Lower Cave of the Zhoukoudian cave complex, China, is one of the most important Middle Pleistocene paleoanthropological and archaeological sites worldwide, with the remains of c. 45 Homo erectus individuals, 98 mammalian taxa, and thousands of lithic tools recovered. Most of the material collected before World War II was lost. However, besides two postcranial elements rediscovered in China in 1951, four human permanent teeth from the 'Dragon Bone Hill,' collected by O. Zdansky between 1921 and 1923, were at the time brought to the Paleontological Institute of Uppsala University, Sweden, where they are still stored. This small sample consists of an upper canine (PMU 25719), an upper third molar (PMU M3550), a lower third premolar crown (PMU M3549), and a lower fourth premolar (PMU M3887). Some researchers have noted the existence of morpho-dimensional differences between the Zhoukoudian and the H. erectus dental assemblage from Sangiran, Java. However, compared to its chrono-geographical distribution, the Early to Middle Pleistocene dental material currently forming the Chinese-Indonesian H. erectus hypodigm is quantitatively meager and still poorly characterized for the extent of its endostructural variation. We used micro-focus X-ray tomography techniques of virtual imaging coupled with geometric morphometrics for comparatively investigating the endostructural conformation (tissue proportions, enamel thickness distribution, enamel-dentine junction morphology, pulp cavity shape) of the four specimens stored in Uppsala, all previously reported for their outer features. The results suggest the existence of time-related differences between continental and insular Southeast Asian dental assemblages, the Middle Pleistocene Chinese teeth apparently retaining an inner signature closer to the likely primitive condition represented by the Early Pleistocene remains from Java, while the Indonesian stock evolved toward tooth structural simplification.}, } @article {pmid29477028, year = {2018}, author = {Takhaveev, V and Heinemann, M}, title = {Metabolic heterogeneity in clonal microbial populations.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {30-38}, doi = {10.1016/j.mib.2018.02.004}, pmid = {29477028}, issn = {1879-0364}, abstract = {In the past decades, numerous instances of phenotypic diversity were observed in clonal microbial populations, particularly, on the gene expression level. Much less is, however, known about phenotypic differences that occur on the level of metabolism. This is likely explained by the fact that experimental tools probing metabolism of single cells are still at an early stage of development. Here, we review recent exciting discoveries that point out different causes for metabolic heterogeneity within clonal microbial populations. These causes range from ecological factors and cell-inherent dynamics in constant environments to molecular noise in gene expression that propagates into metabolism. Furthermore, we provide an overview of current methods to quantify the levels of metabolites and biomass components in single cells.}, } @article {pmid29477022, year = {2018}, author = {Buttigieg, PL and Fadeev, E and Bienhold, C and Hehemann, L and Offre, P and Boetius, A}, title = {Marine microbes in 4D-using time series observation to assess the dynamics of the ocean microbiome and its links to ocean health.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {169-185}, doi = {10.1016/j.mib.2018.01.015}, pmid = {29477022}, issn = {1879-0364}, mesh = {*Ecosystem ; *Microbiota ; *Oceans and Seas ; Phytoplankton/*ultrastructure ; Seawater/analysis/chemistry/*microbiology ; Time Factors ; }, abstract = {Microbial observation is of high relevance in assessing marine phenomena of scientific and societal concern including ocean productivity, harmful algal blooms, and pathogen exposure. However, we have yet to realise its potential to coherently and comprehensively report on global ocean status. The ability of satellites to monitor the distribution of phytoplankton has transformed our appreciation of microbes as the foundation of key ecosystem services; however, more in-depth understanding of microbial dynamics is needed to fully assess natural and anthropogenically induced variation in ocean ecosystems. While this first synthesis shows that notable efforts exist, vast regions such as the ocean depths, the open ocean, the polar oceans, and most of the Southern Hemisphere lack consistent observation. To secure a coordinated future for a global microbial observing system, existing long-term efforts must be better networked to generate shared bioindicators of the Global Ocean's state and health.}, } @article {pmid29476908, year = {2018}, author = {Brusquetti, F and Netto, F and Baldo, D and Haddad, CFB}, title = {What happened in the South American Gran Chaco? Diversification of the endemic frog genus Lepidobatrachus Budgett, 1899 (Anura: Ceratophryidae).}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {123-136}, doi = {10.1016/j.ympev.2018.02.010}, pmid = {29476908}, issn = {1095-9513}, mesh = {Animal Migration ; Animals ; Anura/genetics/*physiology ; Bayes Theorem ; *Biodiversity ; Cluster Analysis ; DNA, Mitochondrial/genetics ; *Ecosystem ; Genetic Variation ; Geography ; Haplotypes/genetics ; Phylogeny ; Population Dynamics ; South America ; Species Specificity ; }, abstract = {The Chaco is one the most neglected and least studied regions of the world. This highly-seasonal semiarid biome is an extensive continuous plain without any geographic barrier, and in spite of its high species diversity, the events and processes responsible have never been assessed. Miocene marine introgressions and Pleistocene glaciations have been mentioned as putative drivers of diversification for some groups of vertebrates in adjacent biomes of southern South America. Here we used multilocus data (one mitochondrial and six nuclear loci) from the three species of the endemic frog genus Lepidobatrachus (Lepidobatrachus asper, Lepidobatrachus laevis, and Lepidobatrachus llanensis) to determine if any of the historical events suggested as drivers of vertebrate diversification in southern South America are related to the diversification of the genus and if the Chaco is indeed a biome without barriers. Using fossil calibration in a coalescent framework we estimated that the genus diversified in the second half of the Miocene, coinciding with marine introgressions. Genetic patterns and historical demography suggest an important role of old archs and cratons as refuges during floods. In one species of the genus, L. llanensis, genetic structure reveals some breaks along the landscape, the main one of which corresponds to an area of the central Chaco that may act as a climatic barrier. Additionally, we found differential effects of the main Chacoan rivers on species of Lepidobatrachus that could be related to the time of persistence of populations in the areas influenced by these rivers.}, } @article {pmid29476907, year = {2018}, author = {Layton, KKS and Gosliner, TM and Wilson, NG}, title = {Flexible colour patterns obscure identification and mimicry in Indo-Pacific Chromodoris nudibranchs (Gastropoda: Chromodorididae).}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {27-36}, doi = {10.1016/j.ympev.2018.02.008}, pmid = {29476907}, issn = {1095-9513}, mesh = {Animals ; Biodiversity ; DNA, Mitochondrial/genetics ; Gastropoda/genetics/*physiology ; Geography ; Likelihood Functions ; Mitochondria/genetics ; Molecular Mimicry/*genetics ; Phylogeny ; Pigmentation/*genetics ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Chromodoris is a genus of colourful nudibranchs that feed on sponges and is found across the Indo-Pacific. While this was once the most diverse chromodorid genus, recent work has shown that the genus should be restricted to a monophyletic lineage that contains only 22 species, all of which exhibit black pigmentation and planar spawning behaviour. Earlier phylogenies of this group are poorly resolved and thus additional work is needed to clarify species boundaries within Chromodoris. This study presents a maximum-likelihood phylogeny based on mitochondrial loci (COI, 16S) for 345 Chromodoris specimens, including data from 323 new specimens and 22 from GenBank, from across the Indo-Pacific. Species hypotheses and phylogenetic analysis uncovered 39 taxa in total containing 18 undescribed species, with only five of 39 taxa showing stable colour patterns and distinct morphotypes. This study also presents the first evidence for regional mimicry in this genus, with C. colemani and C. joshi displaying geographically-based variation in colour patterns which appear to match locally abundant congenerics, highlighting the flexibility of these colour patterns in Chromodoris nudibranchs. The current phylogeny contains short branch lengths, polytomies and poor support at interior nodes, which is indicative of a recent radiation. As such, future work will employ a transcriptome-based exon capture approach for resolving the phylogeny of this group. In all, this study included 21 of the 22 described species in the Chromodoris sensu stricto group with broad sampling coverage from across the Indo-Pacific, constituting the most comprehensive sampling of this group to date. This work highlights several cases of undocumented diversity, ultimately expanding our knowledge of species boundaries in this group, while also demonstrating the limitations of colour patterns for species identification in this genus.}, } @article {pmid29476824, year = {2018}, author = {López-Ramírez, LA and Hernández, NV and Lozoya-Pérez, NE and Lopes-Bezerra, LM and Mora-Montes, HM}, title = {Functional characterization of the Sporothrix schenckii Ktr4 and Ktr5, mannosyltransferases involved in the N-linked glycosylation pathway.}, journal = {Research in microbiology}, volume = {169}, number = {3}, pages = {188-197}, doi = {10.1016/j.resmic.2018.02.004}, pmid = {29476824}, issn = {1769-7123}, mesh = {Candida albicans/physiology ; Cloning, Molecular ; Enzyme Activation ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Glycosylation ; Mannosyltransferases/*genetics/*metabolism ; Metabolic Networks and Pathways ; Multigene Family ; Polysaccharides/metabolism ; Sequence Analysis, DNA ; Sporothrix/*physiology ; }, abstract = {Sporothrix schenckii is one of the causative agents of the deep-seated mycosis sporotrichosis, a fungal infection with worldwide distribution. Fungus-specific molecules and biosynthetic pathways are potential targets for the development of new antifungal drugs. The MNT1/KRE2 gene family is a group of genes that encode fungus-specific Golgi-resident mannosyltransferases that participate in the synthesis of O-linked and N-linked glycans. While this family is composed of five and nine members in Candida albicans and Saccharomyces cerevisiae, respectively, the S. schenckii genome contains only three putative members. MNT1 has been previously characterized as an enzyme that participates in the synthesis of both N-linked and O-linked glycans. Here, we aimed to establish the functional role of the two remaining family members, KTR4 and KTR5, in the protein glycosylation pathways by using heterologous complementation in C. albicans mutants lacking genes of the MNT1/KRE2 family. The two S. schenckii genes restored defects in the elaboration of N-linked glycans, but no complementation of mutants that synthesize truncated O-linked glycans was observed. Therefore, our results suggest that MNT1 is the sole member with a role in O-linked glycan elaboration, whereas the three family members have redundant activity in the S. schenckii N-linked glycan synthesis.}, } @article {pmid29476723, year = {2018}, author = {Fang, Y and Que, J}, title = {Notum balances Wnt signaling during tracheal cartilage development.}, journal = {Developmental biology}, volume = {437}, number = {2}, pages = {61-62}, doi = {10.1016/j.ydbio.2018.02.010}, pmid = {29476723}, issn = {1095-564X}, support = {R01 DK113144/DK/NIDDK NIH HHS/United States ; R01 HL132996/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cartilage/embryology/metabolism ; Chondrogenesis/*genetics ; Esterases/*metabolism ; Mice ; Signal Transduction ; Trachea/embryology/*metabolism ; Wnt Proteins/*metabolism ; }, } @article {pmid29476722, year = {2018}, author = {Zhang, S and Fan, Z and Qiao, P and Zhao, Y and Wang, Y and Jiang, D and Wang, X and Zhu, X and Zhang, Y and Huang, B and Lu, J and Li, X}, title = {miR-51 regulates GABAergic synapses by targeting Rab GEF GLO-4 and lysosomal trafficking-related GLO/AP-3 pathway in Caenorhabditis elegans.}, journal = {Developmental biology}, volume = {436}, number = {1}, pages = {66-74}, doi = {10.1016/j.ydbio.2018.02.009}, pmid = {29476722}, issn = {1095-564X}, mesh = {Adaptor Protein Complex 3/metabolism ; Animals ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/*metabolism ; Cell Culture Techniques ; GABAergic Neurons/*metabolism/physiology ; Guanine Nucleotide Exchange Factors/*metabolism ; Lysosomes/metabolism/physiology ; MicroRNAs/*metabolism ; Protein Transport/*genetics/physiology ; Signal Transduction/genetics ; Synapses/metabolism ; Synaptic Transmission/physiology ; }, abstract = {A deficit of GABA (γ-aminobutyric acid) transmission will lead to epilepsy and other cognitive disorders. Recent evidence has shown that neuronal miRNAs affect various synapses, including GABAergic synapses. However, the miRNAs that control GABAergic synapses remain not fully understood. Here, we identified miR-51, a member of Caenorhabditis elegans miR-99/100 family, as a key regulator of GABAergic synapses. Loss of mir-51 increased PTZ (Pentylenetetrazole) and aldicarb hypersensitivities, and decreased the number of GABAergic synapses and abundance of GABAA receptors. A Rab guaninenucleotide exchange factor (GEF) GLO-4, a well-known component in lysosomal trafficking-related GLO-4/GLO-1/AP-3 (GLO/AP-3) pathway, was discovered to be the direct target of miR-51. Rescue experiments showed that GLO-4 expressed in GABAergic motor neurons functioned as a suppressor of miR-51. Disruption of glo-1 or AP-3 gene apm-3 attenuated the defects of GABAergic synapse in mir-51 mutants, suggesting miR-51 regulated GABAergic synapses through GLO/AP-3 pathway. The present study implies the essential roles of miRNAs on the nervous pathologies characterized by mis-regulated GABA signaling, such as epilepsy.}, } @article {pmid29476564, year = {2018}, author = {Joganic, JL and Dal Pesco, F}, title = {Frontiers in baboon research: an integrative symposium.}, journal = {Evolutionary anthropology}, volume = {27}, number = {2}, pages = {71-73}, doi = {10.1002/evan.21575}, pmid = {29476564}, issn = {1520-6505}, } @article {pmid29476013, year = {2018}, author = {Sowa, AS and Martin, E and Martins, IM and Schmidt, J and Depping, R and Weber, JJ and Rother, F and Hartmann, E and Bader, M and Riess, O and Tricoire, H and Schmidt, T}, title = {Karyopherin α-3 is a key protein in the pathogenesis of spinocerebellar ataxia type 3 controlling the nuclear localization of ataxin-3.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2624-E2633}, pmid = {29476013}, issn = {1091-6490}, mesh = {Active Transport, Cell Nucleus/*genetics ; Animals ; Ataxin-3/*genetics/metabolism ; DNA Repeat Expansion ; Disease Models, Animal ; Drosophila ; Female ; HEK293 Cells ; Humans ; Machado-Joseph Disease/*genetics/metabolism ; Male ; Mice ; Mice, Knockout ; Peptides ; alpha Karyopherins/*genetics/metabolism ; }, abstract = {Spinocerebellar ataxia type 3 (SCA3) is a neurodegenerative disorder caused by a CAG expansion in the ATXN3 gene leading to a polyglutamine expansion in the ataxin-3 protein. The nuclear presence and aggregation of expanded ataxin-3 are critical steps in disease pathogenesis. To identify novel therapeutic targets, we investigated the nucleocytoplasmic transport system by screening a collection of importins and exportins that potentially modulate this nuclear localization. Using cell, Drosophila, and mouse models, we focused on three transport proteins, namely, CRM1, IPO13, KPNA3, and their respective Drosophila orthologs Emb, Cdm, and Kap-α3. While overexpression of CRM1/Emb demonstrated positive effects in Drosophila, KPNA3/Kap-α3 emerged as the most promising target, as knockdown via multiple RNAi lines demonstrated its ability to shuttle both truncated and full-length expanded ataxin-3, rescue neurodegeneration, restore photoreceptor formation, and reduce aggregation. Furthermore, KPNA3 knockout in SCA3 mice resulted in an amelioration of molecular and behavioral disturbances such as total activity, anxiety, and gait. Since KPNA3 is known to function as an import protein and recognize nuclear localization signals (NLSs), this work unites ataxin-3 structure to the nuclear pore machinery and provides a link between karyopherins, NLS signals, and polyglutamine disease, as well as demonstrates that KPNA3 is a key player in the pathogenesis of SCA3.}, } @article {pmid29476012, year = {2018}, author = {Panduro, M and Benoist, C and Mathis, D}, title = {Treg cells limit IFN-γ production to control macrophage accrual and phenotype during skeletal muscle regeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2585-E2593}, pmid = {29476012}, issn = {1091-6490}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 AR070334/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Cardiotoxins/toxicity ; Cells, Cultured ; Female ; Interferon-gamma/*metabolism ; Macrophages/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Muscle, Skeletal/*cytology/injuries/metabolism/*physiology ; Phenotype ; Regeneration/*physiology ; T-Lymphocytes, Regulatory/*metabolism/physiology ; }, abstract = {Skeletal muscle regeneration is a highly orchestrated process that depends on multiple immune-system cell types, notably macrophages (MFs) and Foxp3+CD4+ regulatory T (Treg) cells. This study addressed how Treg cells rein in MFs during regeneration of murine muscle after acute injury with cardiotoxin. We first delineated and characterized two subsets of MFs according to their expression of major histocompatibility complex class II (MHCII) molecules, i.e., their ability to present antigens. Then, we assessed the impact of Treg cells on these MF subsets by punctually depleting Foxp3+ cells during the regenerative process. Treg cells controlled both the accumulation and phenotype of the two types of MFs. Their absence after injury promoted IFN-γ production, primarily by NK and effector T cells, which ultimately resulted in MF dysregulation and increased inflammation and fibrosis, pointing to compromised muscle repair. Thus, we uncovered an IFN-γ-centered regulatory layer by which Treg cells keep MFs in check and dampen inflammation during regeneration of skeletal muscle.}, } @article {pmid29476011, year = {2018}, author = {El-Khatib, M and Nasrallah, C and Lopes, J and Tran, QT and Tetreau, G and Basbous, H and Fenel, D and Gallet, B and Lethier, M and Bolla, JM and Pagès, JM and Vivaudou, M and Weik, M and Winterhalter, M and Colletier, JP}, title = {Porin self-association enables cell-to-cell contact in Providencia stuartii floating communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2220-E2228}, pmid = {29476011}, issn = {1091-6490}, mesh = {Bacterial Outer Membrane Proteins/genetics/metabolism ; *Biofilms ; Crystallography, X-Ray ; Dimerization ; Porins/chemistry/genetics/*metabolism ; Providencia/chemistry/genetics/*physiology ; }, abstract = {The gram-negative pathogen Providencia stuartii forms floating communities within which adjacent cells are in apparent contact, before depositing as canonical surface-attached biofilms. Because porins are the most abundant proteins in the outer membrane of gram-negative bacteria, we hypothesized that they could be involved in cell-to-cell contact and undertook a structure-function relationship study on the two porins of P. stuartii, Omp-Pst1 and Omp-Pst2. Our crystal structures reveal that these porins can self-associate through their extracellular loops, forming dimers of trimers (DOTs) that could enable cell-to-cell contact within floating communities. Support for this hypothesis was obtained by studying the porin-dependent aggregation of liposomes and model cells. The observation that facing channels are open in the two porin structures suggests that DOTs could not only promote cell-to-cell contact but also contribute to intercellular communication.}, } @article {pmid29476010, year = {2018}, author = {Pollock, SB and Hu, A and Mou, Y and Martinko, AJ and Julien, O and Hornsby, M and Ploder, L and Adams, JJ and Geng, H and Müschen, M and Sidhu, SS and Moffat, J and Wells, JA}, title = {Highly multiplexed and quantitative cell-surface protein profiling using genetically barcoded antibodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2836-2841}, pmid = {29476010}, issn = {1091-6490}, support = {R35 GM122451/GM/NIGMS NIH HHS/United States ; 365646//CIHR/Canada ; 342551//CIHR/Canada ; R01 CA191018/CA/NCI NIH HHS/United States ; S10 OD018174/OD/NIH HHS/United States ; P41 CA196276/CA/NCI NIH HHS/United States ; T32 GM064337/GM/NIGMS NIH HHS/United States ; }, mesh = {Antibodies/*analysis/genetics ; Bacteriophages/genetics/metabolism ; Burkitt Lymphoma/*genetics/metabolism ; Cell Line, Tumor ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Leukemia/*genetics/metabolism ; Membrane Proteins/chemistry/*genetics/metabolism ; Proteomics/*methods ; }, abstract = {Human cells express thousands of different surface proteins that can be used for cell classification, or to distinguish healthy and disease conditions. A method capable of profiling a substantial fraction of the surface proteome simultaneously and inexpensively would enable more accurate and complete classification of cell states. We present a highly multiplexed and quantitative surface proteomic method using genetically barcoded antibodies called phage-antibody next-generation sequencing (PhaNGS). Using 144 preselected antibodies displayed on filamentous phage (Fab-phage) against 44 receptor targets, we assess changes in B cell surface proteins after the development of drug resistance in a patient with acute lymphoblastic leukemia (ALL) and in adaptation to oncogene expression in a Myc-inducible Burkitt lymphoma model. We further show PhaNGS can be applied at the single-cell level. Our results reveal that a common set of proteins including FLT3, NCR3LG1, and ROR1 dominate the response to similar oncogenic perturbations in B cells. Linking high-affinity, selective, genetically encoded binders to NGS enables direct and highly multiplexed protein detection, comparable to RNA-sequencing for mRNA. PhaNGS has the potential to profile a substantial fraction of the surface proteome simultaneously and inexpensively to enable more accurate and complete classification of cell states.}, } @article {pmid29476009, year = {2018}, author = {Miller, LS and Simon, SI}, title = {Neutrophils in hot pursuit of MRSA in the lymph nodes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2272-2274}, pmid = {29476009}, issn = {1091-6490}, support = {R01 AI047294/AI/NIAID NIH HHS/United States ; R01 AI129302/AI/NIAID NIH HHS/United States ; R01 AR069502/AR/NIAMS NIH HHS/United States ; R21 AI126896/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Lymph Nodes ; Lymphatic Metastasis ; *Methicillin-Resistant Staphylococcus aureus ; *Neutrophils ; }, } @article {pmid29476008, year = {2018}, author = {Floros, KV and Lochmann, TL and Hu, B and Monterrubio, C and Hughes, MT and Wells, JD and Morales, CB and Ghotra, MS and Costa, C and Souers, AJ and Boikos, SA and Leverson, JD and Tan, M and Serra, V and Koblinski, JE and Arribas, J and Prat, A and Paré, L and Miller, TW and Dozmorov, MG and Harada, H and Windle, BE and Scaltriti, M and Faber, AC}, title = {Coamplification of miR-4728 protects HER2-amplified breast cancers from targeted therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2594-E2603}, pmid = {29476008}, issn = {1091-6490}, support = {K22 CA175276/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA016059/CA/NCI NIH HHS/United States ; }, mesh = {Antineoplastic Agents/pharmacology ; Apoptosis/drug effects ; Breast Neoplasms/*genetics/metabolism ; Cell Line, Tumor ; Drug Resistance, Neoplasm/*genetics ; Female ; Gene Amplification/*genetics ; Humans ; MicroRNAs/*genetics/metabolism ; Protein Kinase Inhibitors/pharmacology ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; Receptor, ErbB-2/*antagonists & inhibitors/*genetics/metabolism ; }, abstract = {HER2 (ERBB2) amplification is a driving oncogenic event in breast cancer. Clinical trials have consistently shown the benefit of HER2 inhibitors (HER2i) in treating patients with both local and advanced HER2+ breast cancer. Despite this benefit, their efficacy as single agents is limited, unlike the robust responses to other receptor tyrosine kinase inhibitors like EGFR inhibitors in EGFR-mutant lung cancer. Interestingly, the lack of HER2i efficacy occurs despite sufficient intracellular signaling shutdown following HER2i treatment. Exploring possible intrinsic causes for this lack of response, we uncovered remarkably depressed levels of NOXA, an endogenous inhibitor of the antiapoptotic MCL-1, in HER2-amplified breast cancer. Upon investigation of the mechanism leading to low NOXA, we identified a micro-RNA encoded in an intron of HER2, termed miR-4728, that targets the mRNA of the Estrogen Receptor α (ESR1). Reduced ESR1 expression in turn prevents ERα-mediated transcription of NOXA, mitigating apoptosis following treatment with the HER2i lapatinib. Importantly, resistance can be overcome with pharmacological inhibition of MCL-1. More generally, while many cancers like EGFR-mutant lung cancer are driven by activated kinases that when drugged lead to robust monotherapeutic responses, we demonstrate that the efficacy of targeted therapies directed against oncogenes active through focal amplification may be mitigated by coamplified genes.}, } @article {pmid29475741, year = {2018}, author = {Thomas, F and Kareva, I and Raven, N and Hamede, R and Pujol, P and Roche, B and Ujvari, B}, title = {Evolved Dependence in Response to Cancer.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {269-276}, doi = {10.1016/j.tree.2018.01.012}, pmid = {29475741}, issn = {1872-8383}, mesh = {*Biological Evolution ; Eukaryota/*genetics ; Evolution, Molecular ; Neoplasms/*genetics/prevention & control/therapy ; *Selection, Genetic ; }, abstract = {Evolved dependence is a process through which one species becomes 'dependent' on another following a long evolutionary history of interaction. This happens when adaptations selected in the first species for interacting lead to fitness costs when the second species is not encountered. Evolved dependence is frequent in host-parasite interactions, where hosts may achieve a higher fitness in the presence of the parasite than in its absence. Since oncogenic manifestations are (i) ubiquitous across multicellular life, (ii) involved in parasitic-like interactions with their hosts, and (iii) have effectively driven the selection of numerous adaptations, it is possible that multicellular organisms display evolved dependence in response to oncogenic processes. We provide a comprehensive overview of the topic, including the implications for cancer prevention and treatment.}, } @article {pmid29475625, year = {2018}, author = {Morlot, C and Rodrigues, CDA}, title = {The New Kid on the Block: A Specialized Secretion System during Bacterial Sporulation.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {663-676}, doi = {10.1016/j.tim.2018.01.001}, pmid = {29475625}, issn = {1878-4380}, abstract = {The transport of proteins across the bacterial cell envelope is mediated by protein complexes called specialized secretion systems. These nanomachines exist in both Gram-positive and Gram-negative bacteria and have been categorized into different types based on their structural components and function. Interestingly, multiple studies suggest the existence of a protein complex in endospore-forming bacteria that appears to be a new type of specialized secretion system. This protein complex is called the SpoIIIA-SpoIIQ complex and is an exception to the categorical norm since it appears to be a hybrid composed of different parts from well-defined specialized secretion systems. Here we summarize and discuss the current understanding of this complex and its potential role as a specialized secretion system.}, } @article {pmid29475454, year = {2018}, author = {Willi, LMV and Labarthe, NV and d'Escoffier, LN and Paiva, JP and de Miranda, MGN and Mendes-de-Almeida, F and Zaverucha do Valle, T}, title = {Can P-glycoprotein and β-tubulin polymorphisms be used as genetic markers of resistance in Dirofilaria immitis from Rio de Janeiro, Brazil?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {152}, pmid = {29475454}, issn = {1756-0500}, mesh = {ATP Binding Cassette Transporter, Subfamily B, Member 1/*genetics ; Animals ; Anthelmintics/*pharmacology ; Brazil ; *Dirofilaria immitis/drug effects/genetics ; *Dirofilariasis/drug therapy/parasitology ; *Dog Diseases/drug therapy/parasitology ; Dogs ; Drug Resistance/*genetics ; Genetic Markers/*genetics ; Lactones/pharmacology ; Macrocyclic Compounds/*pharmacology ; Polymorphism, Single Nucleotide ; Tubulin/*genetics ; }, abstract = {OBJECTIVE: Dirofilaria immitis, the causative agent of canine heartworm infection, is worldwide the most important filarid to affect domestic dogs. Prevention of this infection is done by macrocyclic lactones, but some reports on the lack of efficacy have been published. Although the actual cause of resistance is unknown, single nucleotide polymorphisms (SNPs) on a P-glycoprotein ABC transporter and β-tubulin genes have been pointed out as candidates for genetic markers of resistance. We conducted a survey to verify the presence of these suggested genetic markers in microfilariae from 30 naturally infected dogs under macrocyclic lactones treatment living in an endemic area in the state of Rio de Janeiro.

RESULTS: The analysis of these specific SNPs demonstrated no sign of polymorphism on the P-glycoprotein loci, while 72 and 48% of the samples were polymorphic to the first and second SNPs on β-tubulin loci, respectively. This work demonstrates that the P-glycoprotein position 11 and 618 were not polymorphic and, therefore, not suitable as a genetic marker of resistance in Rio de Janeiro whereas both β-tubulin loci were polimorphic. This work points out the difficulty of finding a universal genetic marker for resistance.}, } @article {pmid29475451, year = {2018}, author = {Berman, GJ}, title = {Measuring behavior across scales.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {23}, pmid = {29475451}, issn = {1741-7007}, support = {R01 MH115831/MH/NIMH NIH HHS/United States ; 1R01MH115831-01//National Institute of Mental Health (US)/International ; }, abstract = {The need for high-throughput, precise, and meaningful methods for measuring behavior has been amplified by our recent successes in measuring and manipulating neural circuitry. The largest challenges associated with moving in this direction, however, are not technical but are instead conceptual: what numbers should one put on the movements an animal is performing (or not performing)? In this review, I will describe how theoretical and data analytical ideas are interfacing with recently-developed computational and experimental methodologies to answer these questions across a variety of contexts, length scales, and time scales. I will attempt to highlight commonalities between approaches and areas where further advances are necessary to place behavior on the same quantitative footing as other scientific fields.}, } @article {pmid29475447, year = {2018}, author = {Shahen, M and Guo, Z and Shar, AH and Ebaid, R and Tao, Q and Zhang, W and Wu, Z and Bai, Y and Fu, Y and Zheng, C and Wang, H and Shar, PA and Liu, J and Wang, Z and Xiao, W and Wang, Y}, title = {Correction to: dengue virus causes changes of MicroRNA-genes regulatory network revealing potential targets for antiviral drugs.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {21}, doi = {10.1186/s12918-018-0536-3}, pmid = {29475447}, issn = {1752-0509}, abstract = {After publication of the article [1], it has been brought to our attention that an author's name was spelt incorrectly in the original published article. Yonghua Wang was previously spelt "Yonghua Wan". This has now been corrected in the revised version of the article.}, } @article {pmid29474976, year = {2018}, author = {Younger, JL and Strozier, L and Maddox, JD and Nyári, ÁS and Bonfitto, MT and Raherilalao, MJ and Goodman, SM and Reddy, S}, title = {Hidden diversity of forest birds in Madagascar revealed using integrative taxonomy.}, journal = {Molecular phylogenetics and evolution}, volume = {124}, number = {}, pages = {16-26}, doi = {10.1016/j.ympev.2018.02.017}, pmid = {29474976}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; *Biodiversity ; Birds/anatomy & histology/*classification ; *Forests ; Gene Flow ; Genetic Loci ; Haplotypes/genetics ; Islands ; Likelihood Functions ; Madagascar ; *Phylogeny ; Phylogeography ; Principal Component Analysis ; Species Specificity ; }, abstract = {Madagascar is renowned as a global biodiversity hotspot with high levels of microendemism. However, there are few molecular phylogenetic studies of Malagasy birds, particularly for forest-dwelling species, signifying a substantial gap in current measures of species diversity in the absence of genetic data. We evaluated species limits and explored patterns of diversification within the genus Newtonia (Family Vangidae), a group of forest-dwelling songbirds endemic to Madagascar. Our modern systematics approach combined genomic, morphometric, and ecological niche data to analyze the evolutionary history of the group. Our integrative analysis uncovered hidden species-level diversity within N. amphichroa, with two deeply divergent and morphologically distinct lineages isolated in different regions of humid forest. We describe the southern lineage as a new species. Conversely, N. brunneicauda, which we initially hypothesized may harbor cryptic diversity owing to its large distribution spanning a range of habitats, was found to have no distinct lineages and shared haplotypes across much of its distribution. The contrasting diversification patterns between Newtonia lineages may be the result of their elevational tolerances. Newtonia brunneicauda has a broad habitat tolerance and elevational range that appears to have facilitated population expansion and gene flow across the island, limiting opportunities for diversification. On the other hand, N. amphichroa is found predominantly in mid-elevation and montane humid forests, a restriction that appears to have promoted speciation associated with climatic fluctuations during the Pleistocene. Our findings indicate that species diversity of Malagasy forest-dwelling birds may be greater than currently recognized, suggesting an urgent need for further studies to quantify biodiversity in Madagascar's rapidly disappearing native forests.}, } @article {pmid29474671, year = {2018}, author = {DeWitt, WS and Mesin, L and Victora, GD and Minin, VN and Matsen, FA}, title = {Using Genotype Abundance to Improve Phylogenetic Inference.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1253-1265}, pmid = {29474671}, issn = {1537-1719}, support = {R01 AI119006/AI/NIAID NIH HHS/United States ; R01 AI120961/AI/NIAID NIH HHS/United States ; R01 GM113246/GM/NIGMS NIH HHS/United States ; T32 HG000035/HG/NHGRI NIH HHS/United States ; }, abstract = {Modern biological techniques enable very dense genetic sampling of unfolding evolutionary histories, and thus frequently sample some genotypes multiple times. This motivates strategies to incorporate genotype abundance information in phylogenetic inference. In this article, we synthesize a stochastic process model with standard sequence-based phylogenetic optimality, and show that tree estimation is substantially improved by doing so. Our method is validated with extensive simulations and an experimental single-cell lineage tracing study of germinal center B cell receptor affinity maturation.}, } @article {pmid29474601, year = {2018}, author = {Malinsky, M and Trucchi, E and Lawson, DJ and Falush, D}, title = {RADpainter and fineRADstructure: Population Inference from RADseq Data.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1284-1290}, pmid = {29474601}, issn = {1537-1719}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Powerful approaches to inferring recent or current population structure based on nearest neighbor haplotype "coancestry" have so far been inaccessible to users without high quality genome-wide haplotype data. With a boom in nonmodel organism genomics, there is a pressing need to bring these methods to communities without access to such data. Here, we present RADpainter, a new program designed to infer the coancestry matrix from restriction-site-associated DNA sequencing (RADseq) data. We combine this program together with a previously published MCMC clustering algorithm into fineRADstructure-a complete, easy to use, and fast population inference package for RADseq data (https://github.com/millanek/fineRADstructure; last accessed February 24, 2018). Finally, with two example data sets, we illustrate its use, benefits, and robustness to missing RAD alleles in double digest RAD sequencing.}, } @article {pmid29474580, year = {2018}, author = {Hu, H and Liu, JM and Hu, Z and Jiang, X and Yang, X and Li, J and Zhang, Y and Yu, H and Khaitovich, P}, title = {Recently Evolved Tumor Suppressor Transcript TP73-AS1 Functions as Sponge of Human-Specific miR-941.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1063-1077}, pmid = {29474580}, issn = {1537-1719}, abstract = {MicroRNA (miRNA) sponges are vital components of posttranscriptional gene regulation. Yet, only a limited number of miRNA sponges have been identified. Here, we show that the recently evolved noncoding tumor suppressor transcript, antisense RNA to TP73 gene (TP73-AS1), functions as a natural sponge of human-specific miRNA miR-941. We find unusually nine high-affinity miR-941 binding sites clustering within 1 kb region on TP73-AS1, which forms miR-941 sponge region. This sponge region displays increased sequence constraint only in humans, and its formation can be traced to the tandem expansion of a 71-nt-long sequence containing a single miR-941 binding site in old world monkeys. We further confirm TP73-AS1 functions as an efficient miR-941 sponge based on massive transcriptome data analyses, wound-healing assay, and Argonaute protein immunoprecipitation experiments conducted in cell lines. The expression of miR-941 and its sponge correlate inversely across multiple healthy and cancerous tissues, with miR-941 being highly expressed in tumors and preferentially repressing tumor suppressors. Thus, the TP73-AS1 and miR-941 duo represents an unusual case of the extremely rapid evolution of noncoding regulators controlling cell migration, proliferation, and tumorigenesis.}, } @article {pmid29473821, year = {2018}, author = {Zhao, GY and Shao, F and Zhang, M and Zhang, XJ and Wang, JY and Fan, SJ and Dai, MX}, title = {Luteimonas rhizosphaerae sp. nov., isolated from the rhizosphere of Triticum aestivum L.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1197-1203}, doi = {10.1099/ijsem.0.002649}, pmid = {29473821}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Triticum/*microbiology ; Ubiquinone/chemistry ; Xanthomonadaceae/*classification/genetics/isolation & purification ; }, abstract = {A Gram-stain-negative, rod-shaped bacterium, strain 4-12T, was isolated from the rhizosphere of Triticum aestivum L. from the Xiaokai River irrigation area, China. The isolate grew optimally at 30 °C, pH 7.5-8.0 and with 1.0 % (w/v) NaCl. Based on the 16S rRNA gene sequence and phylogenetic analysis, strain 4-12T belonged to the genus Luteimonas with the highest degree of 16S rRNA gene sequence similarity to Luteimonas tolerans UM1T (97.68 %), followed by Luteimonas terrae THG-MD21T (97.67 %), Lysobacter panaciterrae Gsoil 068T (97.21 %) and Luteimonas aestuarii B9T (97.16 %). However, the DNA-DNA relatedness values between strain 4-12T and closely related Luteimonas strains were well below 40 %. The average nucleotide identity and the Genome-to-Genome Distance Calculator also showed low relatedness (below 95 and 70 %, respectively) between strain 4-12T and the type strains in genus Luteimonas. Ubiquinone-8 was the predominant quinone. The major fatty acids were iso-C15 : 0, iso-C11 : 0, iso-C17 : 0 and iso-C17 : 1ω9c. Polar lipids were dominated by diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and unidentified phospholipids. The DNA G+C content was 69.5 %. According to the phenotypic, genetic and chemotaxonomic data, strain 4-12T is considered to represent a novel species in the genus Luteimonas, for which the name >Luteimonas rhizosphaerae sp. nov. is proposed, with strain 4-12T (=CCTCC AB 2016261T=KCTC 52585T) as the type strain.}, } @article {pmid29473819, year = {2018}, author = {Kämpfer, P and Busse, HJ and Baars, S and Wilharm, G and Glaeser, SP}, title = {Comamonas aquatilis sp. nov., isolated from a garden pond.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1210-1214}, doi = {10.1099/ijsem.0.002652}, pmid = {29473819}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Comamonas/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gardens ; Germany ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Ponds/*microbiology ; Putrescine/analogs & derivatives/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Water Microbiology ; }, abstract = {A beige-pigmented bacterial strain, SB30-Chr27-3T, isolated from a garden pond, was studied for its taxonomic position. Cells of the isolate were rod-shaped and stained Gram-negative. A comparison of the 16S rRNA gene sequence with the sequences of the type strains of the most closely related species showed that the strain belongs to the genus Comamonas and showed highest sequence similarities to the type strains of Comamonas jiangduensis (97.5 %), Comamonas aquatica (97.4 %) and Comamonas phosphati (97.3 %). The 16S rRNA gene sequence similarities to all other Comamonas species were below 97.0 %. The fatty acid profile of strain SB30-Chr27-3T consisted of the major fatty acids C16 : 0, C15 : 0iso 2-OH/ C16 : 1ω7c, C18 : 1ω7c/C18 : 1ω9c and, in a minor amount, C10 : 0 3-OH. Major compounds in the polar lipid profile were phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine and diphosphatidylglycerol. The quinone system was exclusively composed of ubiquinone Q-8. The polyamine pattern contained the major compounds putrescine, cadaverine and 2-hydroxyputrescine. These data and the differentiating biochemical properties indicated that isolate SB30-CHR27-3T represents a novel species of the genus Comamonas, for which we propose the name >Comamonas aquatilis sp. nov. with the type strain SB30-Chr27-3T (=CIP 111491T=CCM 8815T).}, } @article {pmid29473314, year = {2018}, author = {Pacelli, C and Bryan, RA and Onofri, S and Selbmann, L and Zucconi, L and Shuryak, I and Dadachova, E}, title = {The effect of protracted X-ray exposure on cell survival and metabolic activity of fast and slow growing fungi capable of melanogenesis.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {255-263}, doi = {10.1111/1758-2229.12632}, pmid = {29473314}, issn = {1758-2229}, abstract = {The aim of this study was to analyse how protracted exposure to X-rays delivered at low dose rates of 0.0032-0.052 kGy h-1 affects the survival and metabolic activity of two microfungi capable of melanogenesis: fast-growing Cryptococcus neoformans (CN) and slow-growing Cryomyces antarcticus (CA). Melanized CN and CA cells survived the protracted exposure better than non-melanized ones, which was consistent with previous reports on the radioprotective role of melanin in these fungi after high dose rate exposures. The survival data were described by the linear quadratic dose response model. The XTT metabolic profiles were practically identical for melanized CN and CA with activity dose-dependent increasing: no changes in the activity of the non-melanized CN and CA were recorded by this assay. In contrast, the MTT assay, which measures the intracellular energy-related processes, recorded an increase in activity of non-melanized CN and CA cells, but not in their melanized counterparts. This could reflect intensive repair processes initiated by the non-melanized cells post exposure. This study suggests that differences in radiation responses between melanized and non-melanized fungal cells occur over a wide range of radiation dose rates.}, } @article {pmid29473288, year = {2018}, author = {Purahong, W and Wubet, T and Kahl, T and Arnstadt, T and Hoppe, B and Lentendu, G and Baber, K and Rose, T and Kellner, H and Hofrichter, M and Bauhus, J and Krüger, D and Buscot, F}, title = {Increasing N deposition impacts neither diversity nor functions of deadwood-inhabiting fungal communities, but adaptation and functional redundancy ensure ecosystem function.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1693-1710}, doi = {10.1111/1462-2920.14081}, pmid = {29473288}, issn = {1462-2920}, abstract = {Nitrogen deposition can strongly affect biodiversity, but its specific effects on terrestrial microbial communities and their roles for ecosystem functions and processes are still unclear. Here, we investigated the impacts of N deposition on wood-inhabiting fungi (WIF) and their related ecological functions and processes in a highly N-limited deadwood habitat. Based on high-throughput sequencing, enzymatic activity assay and measurements of wood decomposition rates, we show that N addition has no significant effect on the overall WIF community composition or on related ecosystem functions and processes in this habitat. Nevertheless, we detected several switches in presence/absence (gain/loss) of wood-inhabiting fungal OTUs due to the effect of N addition. The responses of WIF differed from previous studies carried out with fungi living in soil and leaf-litter, which represent less N-limited fungal habitats. Our results suggest that adaptation at different levels of organization and functional redundancy may explain this buffered response and the resistant microbial-mediated ecosystem function and processes against N deposition in highly N-limited habitats.}, } @article {pmid29473286, year = {2018}, author = {Xiao, M and Li, M and Reynolds, CS}, title = {Colony formation in the cyanobacterium Microcystis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1399-1420}, doi = {10.1111/brv.12401}, pmid = {29473286}, issn = {1469-185X}, abstract = {Morphological evolution from a unicellular to multicellular state provides greater opportunities for organisms to attain larger and more complex living forms. As the most common freshwater cyanobacterial genus, Microcystis is a unicellular microorganism, with high phenotypic plasticity, which forms colonies and blooms in lakes and reservoirs worldwide. We conducted a systematic review of field studies from the 1990s to 2017 where Microcystis was dominant. Microcystis was detected as the dominant genus in waterbodies from temperate to subtropical and tropical zones. Unicellular Microcystis spp. can be induced to form colonies by adjusting biotic and abiotic factors in laboratory. Colony formation by cell division has been induced by zooplankton filtrate, high Pb2+ concentration, the presence of another cyanobacterium (Cylindrospermopsis raciborskii), heterotrophic bacteria, and by low temperature and light intensity. Colony formation by cell adhesion can be induced by zooplankton grazing, high Ca2+ concentration, and microcystins. We hypothesise that single cells of all Microcystis morphospecies initially form colonies with a similar morphology to those found in the early spring. These colonies gradually change their morphology to that of M. ichthyoblabe, M. wesenbergii and M. aeruginosa with changing environmental conditions. Colony formation provides Microcystis with many ecological advantages, including adaption to varying light, sustained growth under poor nutrient supply, protection from chemical stressors and protection from grazing. These benefits represent passive tactics responding to environmental stress. Microcystis colonies form at the cost of decreased specific growth rates compared with a unicellular habit. Large colony size allows Microcystis to attain rapid floating velocities (maximum recorded for a single colony, ∼ 10.08 m h-1) that enable them to develop and maintain a large biomass near the surface of eutrophic lakes, where they may shade and inhibit the growth of less-buoyant species in deeper layers. Over time, accompanying species may fail to maintain viable populations, allowing Microcystis to dominate. Microcystis blooms can be controlled by artificial mixing. Microcystis colonies and non-buoyant phytoplankton will be exposed to identical light conditions if they are evenly distributed over the water column. In that case, green algae and diatoms, which generally have a higher growth rate than Microcystis, will be more successful. Under such mixing conditions, other phytoplankton taxa could recover and the dominance of Microcystis would be reduced. This review advances our understanding of the factors and mechanisms affecting Microcystis colony formation and size in the field and laboratory through synthesis of current knowledge. The main transition pathways of morphological changes in Microcystis provide an example of the phenotypic plasticity of organisms during morphological evolution from a unicellular to multicellular state. We emphasise that the mechanisms and factors influencing competition among various close morphospecies are sometimes paradoxical because these morphospecies are potentially a single species. Further work is required to clarify the colony-forming process in different Microcystis morphospecies and the seasonal variation in this process. This will allow researchers to grow laboratory cultures that more closely reflect field morphologies and to optimise artificial mixing to manage blooms more effectively.}, } @article {pmid29473283, year = {2018}, author = {Baars, O and Morel, FMM and Zhang, X}, title = {The purple non-sulfur bacterium Rhodopseudomonas palustris produces novel petrobactin-related siderophores under aerobic and anaerobic conditions.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1667-1676}, doi = {10.1111/1462-2920.14078}, pmid = {29473283}, issn = {1462-2920}, abstract = {Many bacteria produce siderophores to bind and take up Fe(III), an essential trace metal with extremely low solubility in oxygenated environments at circumneutral pH. The purple non-sulfur bacterium Rhodopseudomonas palustris str. CGA009 is a metabolically versatile model organism with high iron requirements that is able to grow under aerobic and anaerobic conditions. Siderophore biosynthesis has been predicted by genomic analysis, however, siderophore structures were not identified. Here, we elucidate the structure of two novel siderophores from R. palustris: rhodopetrobactin A and B. Rhodopetrobactins are structural analogues of the known siderophore petrobactin in which the Fe chelating moieties are conserved, including two 3,4-dihydroxybenzoate and a citrate substructure. In the place of two spermidine linker groups in petrobactin, rhodopetrobactins contain two 4,4'-diaminodibutylamine groups of which one or both are acetylated at the central amine. We analyse siderophore production under different growth modes and show that rhodopetrobactins are produced in response to Fe limitation under aerobic as well as under anaerobic conditions. Evaluation of the chemical characteristics of rhodopetrobactins indicates that they are well suited to support Fe acquisition under variable oxygen and light conditions.}, } @article {pmid29473278, year = {2018}, author = {Gao, N and Xia, M and Dai, J and Yu, D and An, W and Li, S and Liu, S and He, P and Zhang, L and Wu, Z and Bi, X and Chen, S and Haft, DH and Qiu, D}, title = {Both widespread PEP-CTERM proteins and exopolysaccharides are required for floc formation of Zoogloea resiniphila and other activated sludge bacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1677-1692}, doi = {10.1111/1462-2920.14080}, pmid = {29473278}, issn = {1462-2920}, abstract = {Bacterial floc formation plays a central role in the activated sludge (AS) process, which has been widely utilized for sewage and wastewater treatment. The formation of AS flocs has long been known to require exopolysaccharide biosynthesis. This study demonstrates an additional requirement for a PEP-CTERM protein in Zoogloea resiniphila, a dominant AS bacterium harboring a large exopolysaccharide biosynthesis gene cluster. Two members of a wide-spread family of high copy number-per-genome PEP-CTERM genes, transcriptionally regulated by the RpoN sigma factor and accessory PrsK-PrsR two-component system and at least one of these, pepA, must be expressed for Zoogloea to build the floc structures that allow gravitational sludge settling and recycling. Without PrsK or PrsR, Zoogloea cells were planktonic rather than flocculated and secreted exopolysaccharides were released into the growth broth in soluble form. Overexpression of PepA could circumvent the requirement of rpoN, prsK and prsR for the floc-forming phenotype by fixing the exopolysaccharides to bacterial cells. However, overexpression of PepA, which underwent post-translational modifications, could not rescue the long-rod morphology of the rpoN mutant. Consistently, PEP-CTERM genes and exopolysaccharide biosynthesis gene cluster are present in the genome of the floc-forming Nitrospira comammox and Mitsuaria strain as well as many other AS bacteria.}, } @article {pmid29473253, year = {2018}, author = {Sahle, Y and Reyes-Centeno, H and Bentz, C}, title = {Modern human origins and dispersal: current state of knowledge and future directions.}, journal = {Evolutionary anthropology}, volume = {27}, number = {2}, pages = {64-67}, doi = {10.1002/evan.21573}, pmid = {29473253}, issn = {1520-6505}, } @article {pmid29473251, year = {2018}, author = {Odorico, A and Rünneburger, E and Le Rouzic, A}, title = {Modelling the influence of parental effects on gene-network evolution.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {687-700}, doi = {10.1111/jeb.13255}, pmid = {29473251}, issn = {1420-9101}, abstract = {Understanding the importance of nongenetic heredity in the evolutionary process is a major topic in modern evolutionary biology. We modified a classical gene-network model by allowing parental transmission of gene expression and studied its evolutionary properties through individual-based simulations. We identified ontogenetic time (i.e. the time gene networks have to stabilize before being submitted to natural selection) as a crucial factor in determining the evolutionary impact of this phenotypic inheritance. Indeed, fast-developing organisms display enhanced adaptation and greater robustness to mutations when evolving in presence of nongenetic inheritance (NGI). In contrast, in our model, long development reduces the influence of the inherited state of the gene network. NGI thus had a negligible effect on the evolution of gene networks when the speed at which transcription levels reach equilibrium is not constrained. Nevertheless, simulations show that intergenerational transmission of the gene-network state negatively affects the evolution of robustness to environmental disturbances for either fast- or slow-developing organisms. Therefore, these results suggest that the evolutionary consequences of NGI might not be sought only in the way species respond to selection, but also on the evolution of emergent properties (such as environmental and genetic canalization) in complex genetic architectures.}, } @article {pmid29472760, year = {2018}, author = {Nazir, F and Ibrahim, M and Zaman, G and Hussain, A and Yar, AM and Bo, Z}, title = {Genetic Diversity and Functional Analysis of Sigma Factors in Enterobacter cloacae Complex Resourced From Various Niche.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934318754878}, pmid = {29472760}, issn = {1176-9343}, abstract = {Sigma factors are bacterial transcription factors that bind the core RNA polymerase and direct transcription initiation at a specific promoter site. These specialized sigma factors bind the promoters of genes appropriate to the environmental conditions and selectively increase the transcription of those genes. Here, we attempt to identify sigma factors in 5 genomes belonging to the Enterobacter cloacae complex (Ecc), a group of gram-negative bacteria that are important nosocomial pathogens. This process includes the identification of orthologous sequences, conserved motifs, domains, families, phylogenetic profiles, and protein-protein associations of these components. Based on the reference genome, genome-wide comparison revealed that the genomes of Enterobacter asburiae JCM6051, Enterobacter nimipressuralis CIP 104980, Enterobacter hormaechei ATCC49162, Enterobacter kobei JCM 8580, and Enterobacter ludwigii EN-119 encode 10 sigma factors that exist in the reference strain Enterobacter cloacae subsp cloacae ATCC13047. Moreover, the sequence similarity, protein domains and families of the sigma factors, protein-protein association, and phylogenetic profile indicate that the sigma factor proteins of these 5 strains may have evolutionary relatedness and functional characteristics important to their various environmental niches. Interestingly, the absence of RpoS in E kobei, which contributes to bacterial survival under environmental stress conditions, indicates that RpoS might have been independently acquired and may play different roles relating to pathogenicity, host range determination, and/or niche adaptation. Future work such as RNA sequencing will be directed towards investigating the roles that these sigma factors play in the biology of the Ecc.}, } @article {pmid29472487, year = {2018}, author = {Forrester, N}, title = {Independent but not alone.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {950}, doi = {10.1126/science.359.6378.950}, pmid = {29472487}, issn = {1095-9203}, } @article {pmid29472486, year = {2018}, author = {Iwano, S and Sugiyama, M and Hama, H and Watakabe, A and Hasegawa, N and Kuchimaru, T and Tanaka, KZ and Takahashi, M and Ishida, Y and Hata, J and Shimozono, S and Namiki, K and Fukano, T and Kiyama, M and Okano, H and Kizaka-Kondoh, S and McHugh, TJ and Yamamori, T and Hioki, H and Maki, S and Miyawaki, A}, title = {Single-cell bioluminescence imaging of deep tissue in freely moving animals.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {935-939}, doi = {10.1126/science.aaq1067}, pmid = {29472486}, issn = {1095-9203}, mesh = {Animals ; Benzothiazoles/chemistry ; Callithrix ; Carcinogenesis/chemistry/pathology ; Corpus Striatum/chemistry/cytology ; Directed Molecular Evolution ; Hippocampus/chemistry ; Luciferases, Firefly/*chemistry/genetics ; Luminescent Measurements/*methods ; Lung/blood supply ; Mice ; Movement ; Neurons/chemistry/*cytology ; Protein Engineering ; Single-Cell Analysis/*methods ; Video Recording ; }, abstract = {Bioluminescence is a natural light source based on luciferase catalysis of its substrate luciferin. We performed directed evolution on firefly luciferase using a red-shifted and highly deliverable luciferin analog to establish AkaBLI, an all-engineered bioluminescence in vivo imaging system. AkaBLI produced emissions in vivo that were brighter by a factor of 100 to 1000 than conventional systems, allowing noninvasive visualization of single cells deep inside freely moving animals. Single tumorigenic cells trapped in the mouse lung vasculature could be visualized. In the mouse brain, genetic labeling with neural activity sensors allowed tracking of small clusters of hippocampal neurons activated by novel environments. In a marmoset, we recorded video-rate bioluminescence from neurons in the striatum, a deep brain area, for more than 1 year. AkaBLI is therefore a bioengineered light source to spur unprecedented scientific, medical, and industrial applications.}, } @article {pmid29472485, year = {2018}, author = {Hochberg, GKA and Shepherd, DA and Marklund, EG and Santhanagoplan, I and Degiacomi, MT and Laganowsky, A and Allison, TM and Basha, E and Marty, MT and Galpin, MR and Struwe, WB and Baldwin, AJ and Vierling, E and Benesch, JLP}, title = {Structural principles that enable oligomeric small heat-shock protein paralogs to evolve distinct functions.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {930-935}, doi = {10.1126/science.aam7229}, pmid = {29472485}, issn = {1095-9203}, support = {R01 GM027616/GM/NIGMS NIH HHS/United States ; }, mesh = {Gene Duplication ; Heat-Shock Proteins, Small/*chemistry/genetics/*physiology ; Protein Conformation ; Protein Domains ; *Protein Multimerization ; Protein Subunits/chemistry/genetics/physiology ; }, abstract = {Oligomeric proteins assemble with exceptional selectivity, even in the presence of closely related proteins, to perform their cellular roles. We show that most proteins related by gene duplication of an oligomeric ancestor have evolved to avoid hetero-oligomerization and that this correlates with their acquisition of distinct functions. We report how coassembly is avoided by two oligomeric small heat-shock protein paralogs. A hierarchy of assembly, involving intermediates that are populated only fleetingly at equilibrium, ensures selective oligomerization. Conformational flexibility at noninterfacial regions in the monomers prevents coassembly, allowing interfaces to remain largely conserved. Homomeric oligomers must overcome the entropic benefit of coassembly and, accordingly, homomeric paralogs comprise fewer subunits than homomers that have no paralogs.}, } @article {pmid29472484, year = {2018}, author = {Vlachogiannis, G and Hedayat, S and Vatsiou, A and Jamin, Y and Fernández-Mateos, J and Khan, K and Lampis, A and Eason, K and Huntingford, I and Burke, R and Rata, M and Koh, DM and Tunariu, N and Collins, D and Hulkki-Wilson, S and Ragulan, C and Spiteri, I and Moorcraft, SY and Chau, I and Rao, S and Watkins, D and Fotiadis, N and Bali, M and Darvish-Damavandi, M and Lote, H and Eltahir, Z and Smyth, EC and Begum, R and Clarke, PA and Hahne, JC and Dowsett, M and de Bono, J and Workman, P and Sadanandam, A and Fassan, M and Sansom, OJ and Eccles, S and Starling, N and Braconi, C and Sottoriva, A and Robinson, SP and Cunningham, D and Valeri, N}, title = {Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {920-926}, pmid = {29472484}, issn = {1095-9203}, support = {//Wellcome Trust/United Kingdom ; //Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antineoplastic Agents/*pharmacology/therapeutic use ; *Drug Resistance, Neoplasm ; Gastrointestinal Neoplasms/*drug therapy/pathology ; Genomics ; Humans ; Mice ; Neoplasm Metastasis ; Organoids/*drug effects/metabolism ; Phenylurea Compounds/pharmacology/therapeutic use ; Precision Medicine/*methods ; Pyridines/pharmacology/therapeutic use ; *Xenograft Model Antitumor Assays ; }, abstract = {Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from metastatic, heavily pretreated colorectal and gastroesophageal cancer patients recruited in phase 1/2 clinical trials. Phenotypic and genotypic profiling of PDOs showed a high degree of similarity to the original patient tumors. Molecular profiling of tumor organoids was matched to drug-screening results, suggesting that PDOs could complement existing approaches in defining cancer vulnerabilities and improving treatment responses. We compared responses to anticancer agents ex vivo in organoids and PDO-based orthotopic mouse tumor xenograft models with the responses of the patients in clinical trials. Our data suggest that PDOs can recapitulate patient responses in the clinic and could be implemented in personalized medicine programs.}, } @article {pmid29472483, year = {2018}, author = {Hoffmann, DL and Standish, CD and García-Diez, M and Pettitt, PB and Milton, JA and Zilhão, J and Alcolea-González, JJ and Cantalejo-Duarte, P and Collado, H and de Balbín, R and Lorblanchet, M and Ramos-Muñoz, J and Weniger, GC and Pike, AWG}, title = {U-Th dating of carbonate crusts reveals Neandertal origin of Iberian cave art.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {912-915}, doi = {10.1126/science.aap7778}, pmid = {29472483}, issn = {1095-9203}, mesh = {Animals ; Anthropology, Cultural ; Carbonates/chemistry ; Caves ; History, Ancient ; Humans ; *Neanderthals ; Paintings/*history ; Spain ; Thorium/analysis ; Uranium/analysis ; }, abstract = {The extent and nature of symbolic behavior among Neandertals are obscure. Although evidence for Neandertal body ornamentation has been proposed, all cave painting has been attributed to modern humans. Here we present dating results for three sites in Spain that show that cave art emerged in Iberia substantially earlier than previously thought. Uranium-thorium (U-Th) dates on carbonate crusts overlying paintings provide minimum ages for a red linear motif in La Pasiega (Cantabria), a hand stencil in Maltravieso (Extremadura), and red-painted speleothems in Ardales (Andalucía). Collectively, these results show that cave art in Iberia is older than 64.8 thousand years (ka). This cave art is the earliest dated so far and predates, by at least 20 ka, the arrival of modern humans in Europe, which implies Neandertal authorship.}, } @article {pmid29472482, year = {2018}, author = {Eyre, BD and Cyronak, T and Drupp, P and De Carlo, EH and Sachs, JP and Andersson, AJ}, title = {Coral reefs will transition to net dissolving before end of century.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {908-911}, doi = {10.1126/science.aao1118}, pmid = {29472482}, issn = {1095-9203}, mesh = {Acids/chemistry ; Animals ; Anthozoa/*growth & development ; Calcification, Physiologic ; Calcium Carbonate/*chemistry ; *Coral Reefs ; Hydrogen-Ion Concentration ; Seawater/*chemistry ; }, abstract = {Ocean acidification refers to the lowering of the ocean's pH due to the uptake of anthropogenic CO2 from the atmosphere. Coral reef calcification is expected to decrease as the oceans become more acidic. Dissolving calcium carbonate (CaCO3) sands could greatly exacerbate reef loss associated with reduced calcification but is presently poorly constrained. Here we show that CaCO3 dissolution in reef sediments across five globally distributed sites is negatively correlated with the aragonite saturation state (Ωar) of overlying seawater and that CaCO3 sediment dissolution is 10-fold more sensitive to ocean acidification than coral calcification. Consequently, reef sediments globally will transition from net precipitation to net dissolution when seawater Ωar reaches 2.92 ± 0.16 (expected circa 2050 CE). Notably, some reefs are already experiencing net sediment dissolution.}, } @article {pmid29472481, year = {2018}, author = {Kroodsma, DA and Mayorga, J and Hochberg, T and Miller, NA and Boerder, K and Ferretti, F and Wilson, A and Bergman, B and White, TD and Block, BA and Woods, P and Sullivan, B and Costello, C and Worm, B}, title = {Tracking the global footprint of fisheries.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {904-908}, doi = {10.1126/science.aao5646}, pmid = {29472481}, issn = {1095-9203}, mesh = {Animals ; Fisheries/*statistics & numerical data/*trends ; *Fishes ; Human Activities ; Humans ; Oceans and Seas ; Ships ; Spatio-Temporal Analysis ; }, abstract = {Although fishing is one of the most widespread activities by which humans harvest natural resources, its global footprint is poorly understood and has never been directly quantified. We processed 22 billion automatic identification system messages and tracked >70,000 industrial fishing vessels from 2012 to 2016, creating a global dynamic footprint of fishing effort with spatial and temporal resolution two to three orders of magnitude higher than for previous data sets. Our data show that industrial fishing occurs in >55% of ocean area and has a spatial extent more than four times that of agriculture. We find that global patterns of fishing have surprisingly low sensitivity to short-term economic and environmental variation and a strong response to cultural and political events such as holidays and closures.}, } @article {pmid29472480, year = {2018}, author = {Basak, C and Fröllje, H and Lamy, F and Gersonde, R and Benz, V and Anderson, RF and Molina-Kescher, M and Pahnke, K}, title = {Breakup of last glacial deep stratification in the South Pacific.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {900-904}, doi = {10.1126/science.aao2473}, pmid = {29472480}, issn = {1095-9203}, abstract = {Stratification of the deep Southern Ocean during the Last Glacial Maximum is thought to have facilitated carbon storage and subsequent release during the deglaciation as stratification broke down, contributing to atmospheric CO2 rise. Here, we present neodymium isotope evidence from deep to abyssal waters in the South Pacific that confirms stratification of the deepwater column during the Last Glacial Maximum. The results indicate a glacial northward expansion of Ross Sea Bottom Water and a Southern Hemisphere climate trigger for the deglacial breakup of deep stratification. It highlights the important role of abyssal waters in sustaining a deep glacial carbon reservoir and Southern Hemisphere climate change as a prerequisite for the destabilization of the water column and hence the deglacial release of sequestered CO2 through upwelling.}, } @article {pmid29472479, year = {2018}, author = {Légaré, MA and Bélanger-Chabot, G and Dewhurst, RD and Welz, E and Krummenacher, I and Engels, B and Braunschweig, H}, title = {Nitrogen fixation and reduction at boron.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {896-900}, doi = {10.1126/science.aaq1684}, pmid = {29472479}, issn = {1095-9203}, abstract = {Currently, the only compounds known to support fixation and functionalization of dinitrogen (N2) under nonmatrix conditions are based on metals. Here we present the observation of N2 binding and reduction by a nonmetal, specifically a dicoordinate borylene. Depending on the reaction conditions under which potassium graphite is introduced as a reductant, N2 binding to two borylene units results in either neutral (B2N2) or dianionic ([B2N2]2-) products that can be interconverted by respective exposure to further reductant or to air. The 15N isotopologues of the neutral and dianionic molecules were prepared with 15N-labeled dinitrogen, allowing observation of the nitrogen nuclei by 15N nuclear magnetic resonance spectroscopy. Protonation of the dianionic compound with distilled water furnishes a diradical product with a central hydrazido B2N2H2 unit. All three products were characterized spectroscopically and crystallographically.}, } @article {pmid29472478, year = {2018}, author = {Li, P and Dolado, I and Alfaro-Mozaz, FJ and Casanova, F and Hueso, LE and Liu, S and Edgar, JH and Nikitin, AY and Vélez, S and Hillenbrand, R}, title = {Infrared hyperbolic metasurface based on nanostructured van der Waals materials.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {892-896}, doi = {10.1126/science.aaq1704}, pmid = {29472478}, issn = {1095-9203}, abstract = {Metasurfaces with strongly anisotropic optical properties can support deep subwavelength-scale confined electromagnetic waves (polaritons), which promise opportunities for controlling light in photonic and optoelectronic applications. We developed a mid-infrared hyperbolic metasurface by nanostructuring a thin layer of hexagonal boron nitride that supports deep subwavelength-scale phonon polaritons that propagate with in-plane hyperbolic dispersion. By applying an infrared nanoimaging technique, we visualize the concave (anomalous) wavefronts of a diverging polariton beam, which represent a landmark feature of hyperbolic polaritons. The results illustrate how near-field microscopy can be applied to reveal the exotic wavefronts of polaritons in anisotropic materials and demonstrate that nanostructured van der Waals materials can form a highly variable and compact platform for hyperbolic infrared metasurface devices and circuits.}, } @article {pmid29472477, year = {2018}, author = {Trocha, P and Karpov, M and Ganin, D and Pfeiffer, MHP and Kordts, A and Wolf, S and Krockenberger, J and Marin-Palomo, P and Weimann, C and Randel, S and Freude, W and Kippenberg, TJ and Koos, C}, title = {Ultrafast optical ranging using microresonator soliton frequency combs.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {887-891}, doi = {10.1126/science.aao3924}, pmid = {29472477}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Light detection and ranging is widely used in science and industry. Over the past decade, optical frequency combs were shown to offer advantages in optical ranging, enabling fast distance acquisition with high accuracy. Driven by emerging high-volume applications such as industrial sensing, drone navigation, or autonomous driving, there is now a growing demand for compact ranging systems. Here, we show that soliton Kerr comb generation in integrated silicon nitride microresonators provides a route to high-performance chip-scale ranging systems. We demonstrate dual-comb distance measurements with Allan deviations down to 12 nanometers at averaging times of 13 microseconds along with ultrafast ranging at acquisition rates of 100 megahertz, allowing for in-flight sampling of gun projectiles moving at 150 meters per second. Combining integrated soliton-comb ranging systems with chip-scale nanophotonic phased arrays could enable compact ultrafast ranging systems for emerging mass applications.}, } @article {pmid29472476, year = {2018}, author = {Suh, MG and Vahala, KJ}, title = {Soliton microcomb range measurement.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {884-887}, doi = {10.1126/science.aao1968}, pmid = {29472476}, issn = {1095-9203}, abstract = {Laser-based range measurement systems are important in many application areas, including autonomous vehicles, robotics, manufacturing, formation flying of satellites, and basic science. Coherent laser ranging systems using dual-frequency combs provide an unprecedented combination of long range, high precision, and fast update rate. We report dual-comb distance measurement using chip-based soliton microcombs. A single pump laser was used to generate dual-frequency combs within a single microresonator as counterpropagating solitons. We demonstrated time-of-flight measurement with 200-nanometer precision at an averaging time of 500 milliseconds within a range ambiguity of 16 millimeters. Measurements at distances up to 25 meters with much lower precision were also performed. Our chip-based source is an important step toward miniature dual-comb laser ranging systems that are suitable for photonic integration.}, } @article {pmid29472475, year = {2018}, author = {}, title = {The perfect postdoc.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {878}, doi = {10.1126/science.359.6378.878-b}, pmid = {29472475}, issn = {1095-9203}, } @article {pmid29472474, year = {2018}, author = {Everett, RA and Miller, AW and Ruiz, GM}, title = {Shifting sands could bring invasive species.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {878}, doi = {10.1126/science.aar7741}, pmid = {29472474}, issn = {1095-9203}, mesh = {*Introduced Species ; *Silicon Dioxide ; Water Pollutants, Chemical/analysis ; }, } @article {pmid29472473, year = {2018}, author = {Parchizadeh, J and Williams, ST}, title = {Waterbirds targeted in Iran's wetlands.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {877-878}, doi = {10.1126/science.aar8560}, pmid = {29472473}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; *Birds ; *Endangered Species ; Iran ; *Wetlands ; }, } @article {pmid29472472, year = {2018}, author = {Marshall, J and Davison, AJ and Kopf, RK and Boutier, M and Stevenson, P and Vanderplasschen, A}, title = {Biocontrol of invasive carp: Risks abound.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {877}, doi = {10.1126/science.aar7827}, pmid = {29472472}, issn = {1095-9203}, support = {MC_UU_12014/3//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Australia ; *Biological Control Agents ; *Carps ; *Herpesviridae/genetics/isolation & purification/pathogenicity ; *Introduced Species ; Risk ; }, } @article {pmid29472471, year = {2018}, author = {Carroll, D and Daszak, P and Wolfe, ND and Gao, GF and Morel, CM and Morzaria, S and Pablos-Méndez, A and Tomori, O and Mazet, JAK}, title = {The Global Virome Project.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {872-874}, doi = {10.1126/science.aap7463}, pmid = {29472471}, issn = {1095-9203}, mesh = {Animals ; Biomedical Research/economics ; Chiroptera/virology ; Communicable Diseases, Emerging/epidemiology/*prevention & control/*virology ; Disease Outbreaks/*prevention & control ; Host-Pathogen Interactions ; Humans ; Pandemics/*prevention & control ; Pilot Projects ; Virus Diseases/epidemiology/*prevention & control/*virology ; Viruses/genetics/*isolation & purification ; Zoonoses/transmission/virology ; }, } @article {pmid29472470, year = {2018}, author = {Broere, DLJ and Holland, PL}, title = {Boron compounds tackle dinitrogen.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {871}, pmid = {29472470}, issn = {1095-9203}, support = {R01 GM065313/GM/NIGMS NIH HHS/United States ; }, mesh = {*Ammonia ; Boron ; Boron Compounds ; *Molybdenum ; }, } @article {pmid29472469, year = {2018}, author = {Good, A}, title = {Toward nitrogen-fixing plants.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {869-870}, doi = {10.1126/science.aas8737}, pmid = {29472469}, issn = {1095-9203}, mesh = {Bacterial Proteins/genetics ; Genetic Engineering ; Nitrogen/*metabolism ; Nitrogen Fixation/*genetics ; Nitrogenase/genetics ; Plants/genetics/*metabolism ; Plants, Genetically Modified/genetics/*metabolism ; }, } @article {pmid29472468, year = {2018}, author = {Nasu, Y and Campbell, RE}, title = {Unnaturally aglow with a bright inner light.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {868-869}, doi = {10.1126/science.aas9159}, pmid = {29472468}, issn = {1095-9203}, mesh = {Luciferases/*metabolism ; *Luminescent Measurements ; *Single-Cell Analysis ; }, } @article {pmid29472467, year = {2018}, author = {Kalinich, M and Haber, DA}, title = {Cancer detection: Seeking signals in blood.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {866-867}, doi = {10.1126/science.aas9102}, pmid = {29472467}, issn = {1095-9203}, support = {R01 CA129933/CA/NCI NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; }, mesh = {*Early Detection of Cancer ; *Health Knowledge, Attitudes, Practice ; Humans ; Neoplasms ; }, } @article {pmid29472466, year = {2018}, author = {Poloczanska, E}, title = {Keeping watch on the ocean.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {864-865}, doi = {10.1126/science.aar7613}, pmid = {29472466}, issn = {1095-9203}, mesh = {Humans ; Oceans and Seas ; }, } @article {pmid29472465, year = {2018}, author = {Mervis, J}, title = {First up: Texas.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {862}, doi = {10.1126/science.359.6378.862}, pmid = {29472465}, issn = {1095-9203}, } @article {pmid29472464, year = {2018}, author = {Mervis, J}, title = {Just add science.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {860-863}, doi = {10.1126/science.359.6378.860}, pmid = {29472464}, issn = {1095-9203}, } @article {pmid29472463, year = {2018}, author = {Wade, L}, title = {'Extinct' Caribbeans have living descendants.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {858}, doi = {10.1126/science.359.6378.858}, pmid = {29472463}, issn = {1095-9203}, mesh = {Caribbean Region ; *DNA, Ancient ; Female ; *Genome, Human ; Humans ; *Women ; }, } @article {pmid29472462, year = {2018}, author = {Kornei, K}, title = {Ocean array alters view of Atlantic conveyor.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {857}, doi = {10.1126/science.359.6378.857}, pmid = {29472462}, issn = {1095-9203}, } @article {pmid29472461, year = {2018}, author = {Normile, D}, title = {Biologist unveils China's first private research university.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {856}, doi = {10.1126/science.359.6378.856}, pmid = {29472461}, issn = {1095-9203}, } @article {pmid29472460, year = {2018}, author = {Stone, R}, title = {Bringing an Iranian oasis back from the dead.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {854-855}, doi = {10.1126/science.359.6378.854}, pmid = {29472460}, issn = {1095-9203}, mesh = {*Air Pollution ; *Environmental Restoration and Remediation ; Humans ; Iran ; *Water Supply ; }, } @article {pmid29472459, year = {2018}, author = {Kupferschmidt, K}, title = {Worms living in your veins? Seventeen volunteers said 'OK'.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {853-854}, doi = {10.1126/science.359.6378.853}, pmid = {29472459}, issn = {1095-9203}, mesh = {Animals ; Cricetinae ; *Drug Discovery ; Healthy Volunteers ; Human Experimentation ; Humans ; Risk ; Risk Assessment ; *Schistosoma mansoni ; *Schistosomiasis mansoni ; *Schistosomicides ; *Vaccines ; }, } @article {pmid29472458, year = {2018}, author = {Appenzeller, T}, title = {Europe's first artists were Neandertals.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {852-853}, doi = {10.1126/science.359.6378.852}, pmid = {29472458}, issn = {1095-9203}, mesh = {Animals ; Caves ; History, Ancient ; Humans ; *Neanderthals ; Paintings/*history ; Spain ; }, } @article {pmid29472457, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {848-851}, doi = {10.1126/science.359.6378.848}, pmid = {29472457}, issn = {1095-9203}, } @article {pmid29472456, year = {2018}, author = {Groves, RM and Murdock, SH}, title = {Science matters for the census.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {847}, doi = {10.1126/science.aat3285}, pmid = {29472456}, issn = {1095-9203}, } @article {pmid29472455, year = {2018}, author = {McArthur, K and Whitehead, LW and Heddleston, JM and Li, L and Padman, BS and Oorschot, V and Geoghegan, ND and Chappaz, S and Davidson, S and San Chin, H and Lane, RM and Dramicanin, M and Saunders, TL and Sugiana, C and Lessene, R and Osellame, LD and Chew, TL and Dewson, G and Lazarou, M and Ramm, G and Lessene, G and Ryan, MT and Rogers, KL and van Delft, MF and Kile, BT}, title = {BAK/BAX macropores facilitate mitochondrial herniation and mtDNA efflux during apoptosis.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {}, doi = {10.1126/science.aao6047}, pmid = {29472455}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Apoptosis ; Cytochromes c/metabolism ; DNA, Mitochondrial/metabolism ; Fibroblasts ; Gene Knockout Techniques ; HeLa Cells ; Humans ; Mice ; Mice, Inbred C57BL ; Mitochondria/*metabolism ; Mitochondrial Membranes/chemistry/*metabolism ; Protein Multimerization ; bcl-2 Homologous Antagonist-Killer Protein/genetics/*metabolism ; bcl-2-Associated X Protein/genetics/*metabolism ; }, abstract = {Mitochondrial apoptosis is mediated by BAK and BAX, two proteins that induce mitochondrial outer membrane permeabilization, leading to cytochrome c release and activation of apoptotic caspases. In the absence of active caspases, mitochondrial DNA (mtDNA) triggers the innate immune cGAS/STING pathway, causing dying cells to secrete type I interferon. How cGAS gains access to mtDNA remains unclear. We used live-cell lattice light-sheet microscopy to examine the mitochondrial network in mouse embryonic fibroblasts. We found that after BAK/BAX activation and cytochrome c loss, the mitochondrial network broke down and large BAK/BAX pores appeared in the outer membrane. These BAK/BAX macropores allowed the inner mitochondrial membrane to herniate into the cytosol, carrying with it mitochondrial matrix components, including the mitochondrial genome. Apoptotic caspases did not prevent herniation but dismantled the dying cell to suppress mtDNA-induced innate immune signaling.}, } @article {pmid29472454, year = {2018}, author = {Hicks Pries, CE and Castanha, C and Porras, R and Phillips, C and Torn, MS}, title = {Response to Comment on "The whole-soil carbon flux in response to warming".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {}, doi = {10.1126/science.aao0457}, pmid = {29472454}, issn = {1095-9203}, mesh = {Carbon ; *Carbon Cycle ; *Soil ; Soil Microbiology ; Temperature ; }, abstract = {Temperature records and model predictions demonstrate that deep soils warm at the same rate as surface soils, contrary to Xiao et al's assertions. In response to Xiao et al's critique of our Q10 analysis, we present the results with all data points included, which show Q10 values of >2 throughout the soil profile, indicating that all soil depths responded to warming.}, } @article {pmid29472453, year = {2018}, author = {Xiao, J and Yu, F and Zhu, W and Xu, C and Zhang, K and Luo, Y and Tiedje, JM and Zhou, J and Cheng, L}, title = {Comment on "The whole-soil carbon flux in response to warming".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {}, doi = {10.1126/science.aao0218}, pmid = {29472453}, issn = {1095-9203}, abstract = {In a compelling study, Hicks Pries et al (Reports, 31 March 2017, p. 1420) showed that 4°C warming enhanced soil CO2 production in the 1-meter soil profile, with all soil depths displaying similar temperature sensitivity (Q10). We argue that some caveats can be identified in their experimental approach and analysis, and that these critically undermine their conclusions and hence their claim that the strength of feedback between the whole-soil carbon and climate has been underestimated in terrestrial models.}, } @article {pmid29472452, year = {2018}, author = {Casari, M and Tagliapietra, C}, title = {Group size in social-ecological systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2728-2733}, pmid = {29472452}, issn = {1091-6490}, mesh = {Cognition ; *Cooperative Behavior ; Decision Making ; *Ecosystem ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; *Interpersonal Relations/history ; Sample Size ; }, abstract = {Cooperation becomes more difficult as a group becomes larger, but it is unclear where it will break down. Here, we study group size within well-functioning social-ecological systems. We consider centuries-old evidence from hundreds of communities in the Alps that harvested common property resources. Results show that the average group size remained remarkably stable over about six centuries, in contrast to a general increase in the regional population. The population more than doubled, but although single groups experienced fluctuations over time, the average group size remained stable. Ecological factors, such as managing forest instead of pasture land, played a minor role in determining group size. The evidence instead indicates that factors related to social interactions had a significant role in determining group size. We discuss possible interpretations of the findings based on constraints in individual cognition and obstacles in collective decision making.}, } @article {pmid29472451, year = {2018}, author = {Johansen, VE and Catón, L and Hamidjaja, R and Oosterink, E and Wilts, BD and Rasmussen, TS and Sherlock, MM and Ingham, CJ and Vignolini, S}, title = {Genetic manipulation of structural color in bacterial colonies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2652-2657}, pmid = {29472451}, issn = {1091-6490}, support = {639088//European Research Council/International ; BB/K014617/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/genetics/metabolism ; Color ; Flavobacterium/*chemistry/*genetics/growth & development/metabolism ; Genetic Engineering ; Photons ; Seaweed/microbiology ; }, abstract = {Naturally occurring photonic structures are responsible for the bright and vivid coloration in a large variety of living organisms. Despite efforts to understand their biological functions, development, and complex optical response, little is known of the underlying genes involved in the development of these nanostructures in any domain of life. Here, we used Flavobacterium colonies as a model system to demonstrate that genes responsible for gliding motility, cell shape, the stringent response, and tRNA modification contribute to the optical appearance of the colony. By structural and optical analysis, we obtained a detailed correlation of how genetic modifications alter structural color in bacterial colonies. Understanding of genotype and phenotype relations in this system opens the way to genetic engineering of on-demand living optical materials, for use as paints and living sensors.}, } @article {pmid29472450, year = {2018}, author = {Best, RB}, title = {Race to the native state.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2267-2269}, pmid = {29472450}, issn = {1091-6490}, mesh = {*Continental Population Groups ; *European Continental Ancestry Group ; Humans ; }, } @article {pmid29472449, year = {2018}, author = {Mukaigasa, K and Tsujita, T and Nguyen, VT and Li, L and Yagi, H and Fuse, Y and Nakajima-Takagi, Y and Kato, K and Yamamoto, M and Kobayashi, M}, title = {Nrf2 activation attenuates genetic endoplasmic reticulum stress induced by a mutation in the phosphomannomutase 2 gene in zebrafish.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2758-2763}, pmid = {29472449}, issn = {1091-6490}, mesh = {Animals ; *Endoplasmic Reticulum Stress ; Glycosylation ; Mutation ; NF-E2-Related Factor 2/genetics/*metabolism ; Phosphotransferases (Phosphomutases)/*genetics/metabolism ; Zebrafish/genetics/*metabolism ; Zebrafish Proteins/*genetics/metabolism ; }, abstract = {Nrf2 plays critical roles in animals' defense against electrophiles and oxidative stress by orchestrating the induction of cytoprotective genes. We previously isolated the zebrafish mutant it768, which displays up-regulated expression of Nrf2 target genes in an uninduced state. In this paper, we determine that the gene responsible for it768 was the zebrafish homolog of phosphomannomutase 2 (Pmm2), which is a key enzyme in the initial steps of N-glycosylation, and its mutation in humans leads to PMM2-CDG (congenital disorders of glycosylation), the most frequent type of CDG. The pmm2it768 larvae exhibited mild defects in N-glycosylation, indicating that the pmm2it768 mutation is a hypomorph, as in human PMM2-CDG patients. A gene expression analysis showed that pmm2it768 larvae display up-regulation of endoplasmic reticulum (ER) stress, suggesting that the activation of Nrf2 was induced by the ER stress. Indeed, the treatment with the ER stress-inducing compounds up-regulated the gstp1 expression in an Nrf2-dependent manner. Furthermore, the up-regulation of gstp1 by the pmm2 inactivation was diminished by knocking down or out double-stranded RNA-activated protein kinase (PKR)-like ER kinase (PERK), one of the main ER stress sensors, suggesting that Nrf2 was activated in response to the ER stress via the PERK pathway. ER stress-induced activation of Nrf2 was reported previously, but the results have been controversial. Our present study clearly demonstrated that ER stress can indeed activate Nrf2 and this regulation is evolutionarily conserved among vertebrates. Moreover, ER stress induced in pmm2it768 mutants was ameliorated by the treatment of the Nrf2-activator sulforaphane, indicating that Nrf2 plays significant roles in the reduction of ER stress.}, } @article {pmid29472448, year = {2018}, author = {Ling, AK and So, CC and Le, MX and Chen, AY and Hung, L and Martin, A}, title = {Double-stranded DNA break polarity skews repair pathway choice during intrachromosomal and interchromosomal recombination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2800-2805}, pmid = {29472448}, issn = {1091-6490}, support = {PJT156330//CIHR/Canada ; }, mesh = {Animals ; B-Lymphocytes/cytology/metabolism ; Chromosomes, Mammalian/*genetics ; Cytidine Deaminase/metabolism ; *DNA Breaks, Double-Stranded ; *DNA End-Joining Repair ; Mice ; *Recombination, Genetic ; Translocation, Genetic ; }, abstract = {Activation-induced cytidine deaminase (AID) inflicts DNA damage at Ig genes to initiate class switch recombination (CSR) and chromosomal translocations. However, the DNA lesions formed during these processes retain an element of randomness, and thus knowledge of the relationship between specific DNA lesions and AID-mediated processes remains incomplete. To identify necessary and sufficient DNA lesions in CSR, the Cas9 endonuclease and nickase variants were used to program DNA lesions at a greater degree of predictability than is achievable with conventional induction of CSR. Here we show that Cas9-mediated nicks separated by up to 250 nucleotides on opposite strands can mediate CSR. Staggered double-stranded breaks (DSBs) result in more end resection and junctional microhomology than blunt DSBs. Moreover, Myc-Igh chromosomal translocations, which are carried out primarily by alternative end joining (A-EJ), were preferentially induced by 5' DSBs. These data indicate that DSBs with 5' overhangs skew intrachromosomal and interchromosomal end-joining toward A-EJ. In addition to lending potential insight to AID-mediated phenomena, this work has broader carryover implications in DNA repair and lymphomagenesis.}, } @article {pmid29472443, year = {2018}, author = {Ganji, M and Shaltiel, IA and Bisht, S and Kim, E and Kalichava, A and Haering, CH and Dekker, C}, title = {Real-time imaging of DNA loop extrusion by condensin.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {102-105}, doi = {10.1126/science.aar7831}, pmid = {29472443}, issn = {1095-9203}, mesh = {Adenosine Triphosphatases/*chemistry ; Adenosine Triphosphate/chemistry ; DNA/*chemistry ; DNA-Binding Proteins/*chemistry ; Hydrolysis ; Multiprotein Complexes/*chemistry ; *Nucleic Acid Conformation ; Saccharomyces cerevisiae Proteins/*chemistry ; Single Molecule Imaging/*methods ; Time Factors ; }, abstract = {It has been hypothesized that SMC protein complexes such as condensin and cohesin spatially organize chromosomes by extruding DNA into large loops. We directly visualized the formation and processive extension of DNA loops by yeast condensin in real time. Our findings constitute unambiguous evidence for loop extrusion. We observed that a single condensin complex is able to extrude tens of kilobase pairs of DNA at a force-dependent speed of up to 1500 base pairs per second, using the energy of adenosine triphosphate hydrolysis. Condensin-induced loop extrusion was strictly asymmetric, which demonstrates that condensin anchors onto DNA and reels it in from only one side. Active DNA loop extrusion by SMC complexes may provide the universal unifying principle for genome organization.}, } @article {pmid29472442, year = {2018}, author = {Gaunitz, C and Fages, A and Hanghøj, K and Albrechtsen, A and Khan, N and Schubert, M and Seguin-Orlando, A and Owens, IJ and Felkel, S and Bignon-Lau, O and de Barros Damgaard, P and Mittnik, A and Mohaseb, AF and Davoudi, H and Alquraishi, S and Alfarhan, AH and Al-Rasheid, KAS and Crubézy, E and Benecke, N and Olsen, S and Brown, D and Anthony, D and Massy, K and Pitulko, V and Kasparov, A and Brem, G and Hofreiter, M and Mukhtarova, G and Baimukhanov, N and Lõugas, L and Onar, V and Stockhammer, PW and Krause, J and Boldgiv, B and Undrakhbold, S and Erdenebaatar, D and Lepetz, S and Mashkour, M and Ludwig, A and Wallner, B and Merz, V and Merz, I and Zaibert, V and Willerslev, E and Librado, P and Outram, AK and Orlando, L}, title = {Ancient genomes revisit the ancestry of domestic and Przewalski's horses.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {111-114}, doi = {10.1126/science.aao3297}, pmid = {29472442}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Animals ; DNA, Ancient ; Genome ; Horses/anatomy & histology/*classification/*genetics ; Phenotype ; Phylogeny ; }, abstract = {The Eneolithic Botai culture of the Central Asian steppes provides the earliest archaeological evidence for horse husbandry, ~5500 years ago, but the exact nature of early horse domestication remains controversial. We generated 42 ancient-horse genomes, including 20 from Botai. Compared to 46 published ancient- and modern-horse genomes, our data indicate that Przewalski's horses are the feral descendants of horses herded at Botai and not truly wild horses. All domestic horses dated from ~4000 years ago to present only show ~2.7% of Botai-related ancestry. This indicates that a massive genomic turnover underpins the expansion of the horse stock that gave rise to modern domesticates, which coincides with large-scale human population expansions during the Early Bronze Age.}, } @article {pmid29472441, year = {2018}, author = {Mi, D and Li, Z and Lim, L and Li, M and Moissidis, M and Yang, Y and Gao, T and Hu, TX and Pratt, T and Price, DJ and Sestan, N and Marín, O}, title = {Early emergence of cortical interneuron diversity in the mouse embryo.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {81-85}, pmid = {29472441}, issn = {1095-9203}, support = {MR/J013137/1//Medical Research Council/United Kingdom ; U01 MH105972/MH/NIMH NIH HHS/United States ; R01 NS095654/NS/NINDS NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cerebral Cortex/*cytology/*embryology ; Embryo, Mammalian/cytology ; Female ; GABAergic Neurons/*classification/cytology/metabolism ; Gene Expression Profiling ; Interneurons/*classification/cytology/metabolism ; Male ; Mice ; Mice, Inbred Strains ; Mitosis/genetics ; Neural Stem Cells/cytology/metabolism ; Neurogenesis/*genetics ; Single-Cell Analysis ; Transcription, Genetic ; Transcriptome ; }, abstract = {GABAergic interneurons (GABA, γ-aminobutyric acid) regulate neural-circuit activity in the mammalian cerebral cortex. These cortical interneurons are structurally and functionally diverse. Here, we use single-cell transcriptomics to study the origins of this diversity in the mouse. We identify distinct types of progenitor cells and newborn neurons in the ganglionic eminences, the embryonic proliferative regions that give rise to cortical interneurons. These embryonic precursors show temporally and spatially restricted transcriptional patterns that lead to different classes of interneurons in the adult cerebral cortex. Our findings suggest that shortly after the interneurons become postmitotic, their diversity is already patent in their diverse transcriptional programs, which subsequently guide further differentiation in the developing cortex.}, } @article {pmid29472440, year = {2018}, author = {Rauer, B and Erne, S and Schweigler, T and Cataldini, F and Tajik, M and Schmiedmayer, J}, title = {Recurrences in an isolated quantum many-body system.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6386}, pages = {307-310}, doi = {10.1126/science.aan7938}, pmid = {29472440}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The complexity of interacting quantum many-body systems leads to exceedingly long recurrence times of the initial quantum state for all but the smallest systems. For large systems, one cannot probe the full quantum state in all its details. Thus, experimentally, recurrences can only be determined on the level of the accessible observables. Realizing a commensurate spectrum of collective excitations in one-dimensional superfluids, we demonstrate recurrences of coherence and long-range order in an interacting quantum many-body system containing thousands of particles. Our findings will enable the study of the coherent dynamics of large quantum systems even after they have reached a transient thermal-like state.}, } @article {pmid29471983, year = {2018}, author = {Chistoserdova, L and Kalyuzhnaya, MG}, title = {Current Trends in Methylotrophy.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {703-714}, doi = {10.1016/j.tim.2018.01.011}, pmid = {29471983}, issn = {1878-4380}, abstract = {Methylotrophy is a field of study dealing with microorganisms capable of utilization of compounds devoid of carbon-carbon bonds (C1 compounds). In this review, we highlight several emerging trends in methylotrophy. First, we discuss the significance of the recent discovery of lanthanide-dependent alcohol dehydrogenases for understanding both the occurrence and the distribution of methylotrophy functions among bacteria, and then we discuss the newly appreciated role of lanthanides in biology. Next, we describe the detection of other methylotrophy pathways across novel bacterial taxa and insights into the evolution of methylotrophy. Further, data are presented on the occurrence and activity of aerobic methylotrophs in hypoxic and anoxic environments, questioning the prior assumptions on niche separation of aerobic and anaerobic methylotrophy. The concept of communal function in aerobic methane oxidation is also briefly discussed. Finally, we review recent research in engineering methylotrophs for biotechnological applications as well as recent progress in engineering synthetic methylotrophy.}, } @article {pmid29471971, year = {2018}, author = {Godoy, O and Bartomeus, I and Rohr, RP and Saavedra, S}, title = {Towards the Integration of Niche and Network Theories.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {287-300}, doi = {10.1016/j.tree.2018.01.007}, pmid = {29471971}, issn = {1872-8383}, mesh = {Biodiversity ; *Ecosystem ; *Models, Biological ; }, abstract = {The quest for understanding how species interactions modulate diversity has progressed by theoretical and empirical advances following niche and network theories. Yet, niche studies have been limited to describe coexistence within tropic levels despite incorporating information about multi-trophic interactions. Network approaches could address this limitation, but they have ignored the structure of species interactions within trophic levels. Here we call for the integration of niche and network theories to reach new frontiers of knowledge exploring how interactions within and across trophic levels promote species coexistence. This integration is possible due to the strong parallelisms in the historical development, ecological concepts, and associated mathematical tools of both theories. We provide a guideline to integrate this framework with observational and experimental studies.}, } @article {pmid29471876, year = {2018}, author = {Tankeu, AT and Azabji-Kenfack, M and Nganou, CN and Ngassam, E and Kuate-Mfeukeu, L and Mba, C and Dehayem, MY and Mbanya, JC and Sobngwi, E}, title = {Effect of propranolol on heart rate variability in hyperthyroidism.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {151}, pmid = {29471876}, issn = {1756-0500}, mesh = {Adrenergic beta-Antagonists/administration & dosage/*pharmacology ; Adult ; Autonomic Nervous System/*drug effects/*physiopathology ; Blood Pressure/*drug effects ; Electrocardiography/*drug effects ; Female ; Heart Rate/*drug effects ; Humans ; Hyperthyroidism/*drug therapy/*physiopathology ; Male ; Middle Aged ; Propranolol/administration & dosage/*pharmacology ; }, abstract = {OBJECTIVES: We aimed to determine the effect of propanolol on heart rate variability (HRV) in hyperthyroidism before antithyroid treatment. This was a before and after study, on ten patients presenting overt hyperthyroidism naïve to treatment. In each patient, a resting electrocardiogram was done followed by estimation of cardiac autonomic dysfunction during five maneuvers (Ewing battery tests). Long term HRV measurement was done using 24 h ambulatory electrocardiographic recording. This automatically provided estimation of HRV using SDNN and RMSSD index, LF, HF, and HF/LF ratio. After baseline investigations, 40 mg of propanolol was given twice a day for 3 days and same parameters were measured after 72 h of treatment.

RESULTS: Our patients were aged 40 ± 10 years. Propanolol significantly reduced RR and HR interval (669 ms vs 763 ms and 91 vs 79 bpm; p < 0.01). QT and PR space were significantly extended (360 vs 384 ms and 133 vs 172 ms; p = 0.01). It increases QRS complex and blood pressure response to sustained handgrip but failed to modify previously decreased heart response to deep breathing. HRV parameters such as SDNN, RMSSD, LF, HF and sympathovagal balance estimate by HF/LF ratio remained unchanged. Although a significant reduction in heart excitability, propanolol failed to restore a good sympathovagal balance in hyperthyroidism. Trial registration NCT03393728 "Retrospectively registered".}, } @article {pmid29471873, year = {2018}, author = {Ahmed, M and Nguyen, H and Lai, T and Kim, DR}, title = {miRCancerdb: a database for correlation analysis between microRNA and gene expression in cancer.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {103}, pmid = {29471873}, issn = {1756-0500}, support = {2015R1A5A2008833//National Research Foundation of Korea/ ; }, mesh = {Atlases as Topic ; *Databases, Genetic ; Genome/*genetics ; Humans ; MicroRNAs/genetics ; Neoplasms/*genetics ; }, abstract = {OBJECTIVES: microRNAs regulate expression of target genes by specifically binding to their transcripts, subsequently leading to translational inhibition or mRNA degradation. Gene regulation by microRNAs has been implicated in a wide range of physiological and pathological conditions. Here, we leverage the use of public-access data and the available genomic annotations to pre-calculate the correlation of the expression of a large number of microRNAs with gene at the mRNA and protein level in the context of cancers.

RESULTS: Expression data of miRNAs, mRNAs and proteins in cancer patients from The Cancer Genome Atlas along with TargetScan miRNAs-target annotations were used to calculate the expression correlations between miRNAs and features (mRNAs/proteins) in a number of cancer studies. We then packed the output of this analysis into a database and made it available through an interactive web application. The miRCancerdb is an easy-to-use database to investigate the microRNAs-dependent regulation of target genes involved in development of cancer.}, } @article {pmid29471872, year = {2018}, author = {Van Goethem, MW and Pierneef, R and Bezuidt, OKI and Van De Peer, Y and Cowan, DA and Makhalanyane, TP}, title = {A reservoir of 'historical' antibiotic resistance genes in remote pristine Antarctic soils.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {40}, pmid = {29471872}, issn = {2049-2618}, support = {93074//National Research Foundation of South Africa/International ; 97891//National Research Foundation of South Africa/International ; 99320//National Research Foundation of South Africa/International ; 110717//National Research Foundation/International ; }, mesh = {Antarctic Regions ; Anti-Bacterial Agents/*metabolism ; Bacteria/*classification/*drug effects ; Drug Resistance, Multiple, Bacterial/*genetics ; Gene Transfer, Horizontal/genetics ; Genes, Bacterial/genetics ; Membrane Transport Proteins/genetics ; Metagenomics/methods ; Soil Microbiology ; }, abstract = {BACKGROUND: Soil bacteria naturally produce antibiotics as a competitive mechanism, with a concomitant evolution, and exchange by horizontal gene transfer, of a range of antibiotic resistance mechanisms. Surveys of bacterial resistance elements in edaphic systems have originated primarily from human-impacted environments, with relatively little information from remote and pristine environments, where the resistome may comprise the ancestral gene diversity.

METHODS: We used shotgun metagenomics to assess antibiotic resistance gene (ARG) distribution in 17 pristine and remote Antarctic surface soils within the undisturbed Mackay Glacier region. We also interrogated the phylogenetic placement of ARGs compared to environmental ARG sequences and tested for the presence of horizontal gene transfer elements flanking ARGs.

RESULTS: In total, 177 naturally occurring ARGs were identified, most of which encoded single or multi-drug efflux pumps. Resistance mechanisms for the inactivation of aminoglycosides, chloramphenicol and β-lactam antibiotics were also common. Gram-negative bacteria harboured most ARGs (71%), with fewer genes from Gram-positive Actinobacteria and Bacilli (Firmicutes) (9%), reflecting the taxonomic composition of the soils. Strikingly, the abundance of ARGs per sample had a strong, negative correlation with species richness (r = - 0.49, P < 0.05). This result, coupled with a lack of mobile genetic elements flanking ARGs, suggests that these genes are ancient acquisitions of horizontal transfer events.

CONCLUSIONS: ARGs in these remote and uncontaminated soils most likely represent functional efficient historical genes that have since been vertically inherited over generations. The historical ARGs in these pristine environments carry a strong phylogenetic signal and form a monophyletic group relative to ARGs from other similar environments.}, } @article {pmid29471810, year = {2018}, author = {Alwin Prem Anand, A and Huber, C and Asnet Mary, J and Gallus, N and Leucht, C and Klafke, R and Hirt, B and Wizenmann, A}, title = {Expression and function of microRNA-9 in the mid-hindbrain area of embryonic chick.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {3}, pmid = {29471810}, issn = {1471-213X}, abstract = {BACKGROUND: MiR-9 is a small non-coding RNA that is highly conserved between species and primarily expressed in the central nervous system (CNS). It is known to influence proliferation and neuronal differentiation in the brain and spinal cord of different vertebrates. Different studies have pointed to regional and species-specific differences in the response of neural progenitors to miR-9.

METHODS: In ovo and ex ovo electroporation was used to overexpress or reduce miR-9 followed by mRNA in situ hybridisation and immunofluorescent stainings to evaluate miR- expression and the effect of changed miR-9 expression.

RESULTS: We have investigated the expression and function of miR-9 during early development of the mid-hindbrain region (MH) in chick. Our analysis reveals a closer relationship of chick miR-9 to mammalian miR-9 than to fish and a dynamic expression pattern in the chick neural tube. Early in development, miR-9 is diffusely expressed in the entire brain, bar the forebrain, and it becomes more restricted to specific areas of the CNS at later stages. MiR-9 overexpression at HH9-10 results in a reduction of FGF8 expression and premature neuronal differentiation in the mid-hindbrain boundary (MHB). Within the midbrain miR-9 does not cause premature neuronal differentiation it rather reduces proliferation in the midbrain.

CONCLUSION: Our findings indicate that miR-9 has regional specific effects in the developing mid-hindbrain region with a divergence of response of regional progenitors.}, } @article {pmid29471808, year = {2018}, author = {Grimholt, U}, title = {Whole genome duplications have provided teleosts with many roads to peptide loaded MHC class I molecules.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {25}, pmid = {29471808}, issn = {1471-2148}, mesh = {Amino Acid Sequence ; Animals ; Antigen Presentation/genetics ; Fishes/*genetics ; *Gene Duplication ; Genes, MHC Class I ; *Genome ; Haplotypes/genetics ; Histocompatibility Antigens Class I/*genetics ; Peptides/genetics/*metabolism ; Phylogeny ; Polymorphism, Genetic ; Species Specificity ; }, abstract = {BACKGROUND: In sharks, chickens, rats, frogs, medaka and zebrafish there is haplotypic variation in MHC class I and closely linked genes involved in antigen processing, peptide translocation and peptide loading. At least in chicken, such MHCIa haplotypes of MHCIa, TAP2 and Tapasin are shown to influence the repertoire of pathogen epitopes being presented to CD8+ T-cells with subsequent effect on cell-mediated immune responses.

RESULTS: Examining MHCI haplotype variation in Atlantic salmon using transcriptome and genome resources we found little evidence for polymorphism in antigen processing genes closely linked to the classical MHCIa genes. Looking at other genes involved in MHCI assembly and antigen processing we found retention of functional gene duplicates originating from the second vertebrate genome duplication event providing cyprinids, salmonids, and neoteleosts with the potential of several different peptide-loading complexes. One of these gene duplications has also been retained in the tetrapod lineage with orthologs in frogs, birds and opossum.

CONCLUSION: We postulate that the unique salmonid whole genome duplication (SGD) is responsible for eliminating haplotypic content in the paralog MHCIa regions possibly due to frequent recombination and reorganization events at early stages after the SGD. In return, multiple rounds of whole genome duplications has provided Atlantic salmon, other teleosts and even lower vertebrates with alternative peptide loading complexes. How this affects antigen presentation remains to be established.}, } @article {pmid29471804, year = {2018}, author = {O'Leary, SJ and Hollenbeck, CM and Vega, RR and Gold, JR and Portnoy, DS}, title = {Genetic mapping and comparative genomics to inform restoration enhancement and culture of southern flounder, Paralichthys lethostigma.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {163}, pmid = {29471804}, issn = {1471-2164}, support = {Subcontract of 56424//State Wildlife Grant/International ; }, mesh = {Animals ; Chromosome Mapping/*methods ; Environment ; Flounder/*genetics ; Genetic Linkage ; Genetic Markers ; Genetic Variation ; Genome ; Genomics/*methods ; *Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; Sequence Analysis, DNA ; Synteny ; }, abstract = {BACKGROUND: Southern flounder, Paralichthys lethostigma, historically support a substantial fishery along the Atlantic and Gulf coasts of the southern United States. Low year-class strengths over the past few years in the western Gulf of Mexico have raised concern that spawning stocks may be overfished. Current management of the resource includes releasing hatchery-raised juveniles to restock bays and estuaries; additionally, there is a growing interest in the potential for commercial aquaculture of the species. Currently, genomic resources for southern flounder do not exist. Here, we used two hatchery-reared families and double-digest, restriction-site-associated DNA (ddRAD) sequencing to create a reduced-representation genomic library consisting of several thousand single nucleotide polymorphisms (SNPs) located throughout the genome.

RESULTS: The relative position of each SNP-containing locus was determined to create a high-density genetic map spanning the 24 linkage groups of the southern flounder genome. The consensus map was used to identify regions of shared synteny between southern flounder and seven other fish species for which genome assemblies are available. Finally, syntenic blocks were used to localize genes identified from transcripts in European flounder as potentially being involved in ecotoxicological and osmoregulatory responses, as well as QTLs associated with growth and disease resistance in Japanese flounder, on the southern flounder linkage map.

CONCLUSIONS: The information provided by the linkage map will enrich restoration efforts by providing a foundation for interpreting spatial genetic variation within the species, ultimately furthering an understanding of the adaptive potential and resilience of southern flounder to future changes in local environmental conditions. Further, the map will facilitate the use of genetic markers to enhance restoration and commercial aquaculture.}, } @article {pmid29471803, year = {2018}, author = {Liu, B and Guan, X and Liang, W and Chen, J and Fang, L and Hu, Y and Guo, W and Rong, J and Xu, G and Zhang, T}, title = {Divergence and evolution of cotton bHLH proteins from diploid to allotetraploid.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {162}, pmid = {29471803}, issn = {1471-2164}, support = {31330058//National Natural Science Foundation of China/International ; BK20150671//the Natural Science Foundation of Jiangsu Province/International ; 2015M581808//China Postdoctoral Science Foundation Funded Project/International ; 1501045A//Jiangsu Planned Projects for Postdoctoral Research Funds/International ; }, mesh = {Basic Helix-Loop-Helix Transcription Factors/*genetics ; Diploidy ; *Evolution, Molecular ; *Gene Expression Regulation, Plant ; Gossypium/*genetics ; Plant Proteins/*genetics ; Polyploidy ; Tetraploidy ; }, abstract = {BACKGROUND: Polyploidy is considered a major driving force in genome expansion, yielding duplicated genes whose expression may be conserved or divergence as a consequence of polyploidization.

RESULTS: We compared the genome sequences of tetraploid cotton (Gossypium hirsutum) and its two diploid progenitors, G. arboreum and G. raimondii, and found that the bHLH genes were conserved over the polyploidization. Oppositely, the expression of the homeolgous gene pairs was diversified. The biased homeologous proportion for bHLH family is significantly higher (64.6%) than the genome wide homeologous expression bias (40%). Compared with cacao (T. cacao), orthologous genes only accounted for a small proportion (41.7%) of whole cotton bHLHs family. The further Ks analysis indicated that bHLH genes underwent at least two distinct episodes of whole genome duplication: a recent duplication (1.0-60.0 million years ago, MYA, 0.005 < Ks < 0.312) and an old duplication (> 60.0 MYA, 0.312 < Ks < 3.0). The old duplication event might have played a key role in the expansion of the bHLH family. Both recent and old duplicated pairs (68.8%) showed a divergent expression profile, indicating specialized functions. The expression diversification of the duplicated genes suggested it might be a universal feature of the long-term evolution of cotton.

CONCLUSIONS: Overview of cotton bHLH proteins indicated a conserved and divergent evolution from diploids to allotetraploid. Our results provided an excellent example for studying the long-term evolution of polyploidy.}, } @article {pmid29471801, year = {2018}, author = {Oluwadare, O and Zhang, Y and Cheng, J}, title = {A maximum likelihood algorithm for reconstructing 3D structures of human chromosomes from chromosomal contact data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {161}, pmid = {29471801}, issn = {1471-2164}, support = {DBI1149224//National Science Foundation/International ; }, mesh = {*Algorithms ; *Chromosomes, Human ; Computational Biology/*methods ; Datasets as Topic ; *Genome, Human ; Humans ; Imaging, Three-Dimensional/*methods ; In Situ Hybridization, Fluorescence ; Likelihood Functions ; Lymphocytes/metabolism ; Models, Molecular ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/genetics ; }, abstract = {BACKGROUND: The development of chromosomal conformation capture techniques, particularly, the Hi-C technique, has made the analysis and study of the spatial conformation of a genome an important topic in bioinformatics and computational biology. Aided by high-throughput next generation sequencing techniques, the Hi-C technique can generate genome-wide, large-scale intra- and inter-chromosomal interaction data capable of describing in details the spatial interactions within a genome. These data can be used to reconstruct 3D structures of chromosomes that can be used to study DNA replication, gene regulation, genome interaction, genome folding, and genome function.

RESULTS: Here, we introduce a maximum likelihood algorithm called 3DMax to construct the 3D structure of a chromosome from Hi-C data. 3DMax employs a maximum likelihood approach to infer the 3D structures of a chromosome, while automatically re-estimating the conversion factor (α) for converting Interaction Frequency (IF) to distance. Our results show that the models generated by 3DMax from a simulated Hi-C dataset match the true models better than most of the existing methods. 3DMax is more robust to structural variability and noise. Compared on a real Hi-C dataset, 3DMax constructs chromosomal models that fit the data better than most methods, and it is faster than all other methods. The models reconstructed by 3DMax were consistent with fluorescent in situ hybridization (FISH) experiments and existing knowledge about the organization of human chromosomes, such as chromosome compartmentalization.

CONCLUSIONS: 3DMax is an effective approach to reconstructing 3D chromosomal models. The results, and the models generated for the simulated and real Hi-C datasets are available here: http://sysbio.rnet.missouri.edu/bdm_download/3DMax/ . The source code is available here: https://github.com/BDM-Lab/3DMax . A short video demonstrating how to use 3DMax can be found here: https://youtu.be/ehQUFWoHwfo .}, } @article {pmid29471790, year = {2018}, author = {De Wit, P and Durland, E and Ventura, A and Langdon, CJ}, title = {Gene expression correlated with delay in shell formation in larval Pacific oysters (Crassostrea gigas) exposed to experimental ocean acidification provides insights into shell formation mechanisms.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {160}, pmid = {29471790}, issn = {1471-2164}, support = {NA14OAR4170064//Oregon Sea Grant, Oregon State University (US)/International ; }, mesh = {Acids/*pharmacology ; Animal Shells/drug effects/*growth & development/metabolism ; Animals ; Biomarkers/metabolism ; Calcification, Physiologic ; Crassostrea/drug effects/genetics/*growth & development ; Gene Expression Regulation/*drug effects ; Larva/drug effects/genetics/growth & development ; Seawater/*chemistry ; }, abstract = {BACKGROUND: Despite recent work to characterize gene expression changes associated with larval development in oysters, the mechanism by which the larval shell is first formed is still largely unknown. In Crassostrea gigas, this shell forms within the first 24 h post fertilization, and it has been demonstrated that changes in water chemistry can cause delays in shell formation, shell deformations and higher mortality rates. In this study, we use the delay in shell formation associated with exposure to CO2-acidified seawater to identify genes correlated with initial shell deposition.

RESULTS: By fitting linear models to gene expression data in ambient and low aragonite saturation treatments, we are able to isolate 37 annotated genes correlated with initial larval shell formation, which can be categorized into 1) ion transporters, 2) shell matrix proteins and 3) protease inhibitors. Clustering of the gene expression data into co-expression networks further supports the result of the linear models, and also implies an important role of dynein motor proteins as transporters of cellular components during the initial shell formation process.

CONCLUSIONS: Using an RNA-Seq approach with high temporal resolution allows us to identify a conceptual model for how oyster larval calcification is initiated. This work provides a foundation for further studies on how genetic variation in these identified genes could affect fitness of oyster populations subjected to future environmental changes, such as ocean acidification.}, } @article {pmid29471787, year = {2018}, author = {Zhang, M and Liu, Y and Shi, H and Guo, M and Chai, M and He, Q and Yan, M and Cao, D and Zhao, L and Cai, H and Qin, Y}, title = {Evolutionary and expression analyses of soybean basic Leucine zipper transcription factor family.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {159}, pmid = {29471787}, issn = {1471-2164}, support = {31522009//National Natural Science Foundation of China/International ; 31470284//National Natural Science Foundation of China/International ; U1605212//National Natural Science Foundation of China/International ; 31600249//National Natural Science Foundation of China/International ; }, mesh = {Basic-Leucine Zipper Transcription Factors/*genetics ; *Evolution, Molecular ; *Gene Expression Regulation, Plant ; Plant Proteins/*genetics ; Soybeans/*genetics ; Stress, Physiological ; }, abstract = {BACKGROUND: Soybean, a major legume crop native to East Asia, presents a wealth of resources for utilization. The basic leucine zipper (bZIP) transcription factors play important roles in various biological processes including developmental regulation and responses to environmental stress stimuli. Currently, little information is available regarding the bZIP family in the legume crop soybean.

RESULTS: Using a genome-wide domain analysis, we identified 160 GmbZIP genes in soybean genome, named from GmbZIP1 to GmbZIP160. These 160GmbZIP genes, distributed unevenly across 20 chromosomes, were grouped into 12 subfamilies based on phylogenetic analysis. Gene structure and conserved motif analyses showed that GmbZIP within the same subfamily shared similar intron-exon organizations and motif composition. Syntenic and phylogenetic analyses identified 40 Arabidopsis bZIP genes and 83 soybean bZIP genes as orthologs. By investigating the expression profiling of GmbZIP in different tissues and under drought and flooding stresses, we showed that a majority of GmbZIP (83.44%) exhibited transcript abundance in all examined tissues and 75.6% displayed transcript changes after drought and flooding treatment, suggesting that GmbZIP may play a broad role in soybean development and response to water stress.

CONCLUSIONS: One hundred sixty GmbZIP genes were identified in soybean genome. Our results provide insights for the evolutionary history of bZIP family in soybean and shed light on future studies on the function of bZIP genes in response to water stress in soybean.}, } @article {pmid29471785, year = {2018}, author = {Leduc-Robert, G and Maddison, WP}, title = {Phylogeny with introgression in Habronattus jumping spiders (Araneae: Salticidae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {24}, pmid = {29471785}, issn = {1471-2148}, mesh = {Animals ; Bayes Theorem ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; *Inbreeding ; *Locomotion ; Models, Genetic ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; Spiders/*classification/genetics ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Habronattus is a diverse clade of jumping spiders with complex courtship displays and repeated evolution of Y chromosomes. A well-resolved species phylogeny would provide an important framework to study these traits, but has not yet been achieved, in part because the few genes available in past studies gave conflicting signals. Such discordant gene trees could be the result of incomplete lineage sorting (ILS) in recently diverged parts of the phylogeny, but there are indications that introgression could be a source of conflict.

RESULTS: To infer Habronattus phylogeny and investigate the cause of gene tree discordance, we assembled transcriptomes for 34 Habronattus species and 2 outgroups. The concatenated 2.41 Mb of nuclear data (1877 loci) resolved phylogeny by Maximum Likelihood (ML) with high bootstrap support (95-100%) at most nodes, with some uncertainty surrounding the relationships of H. icenoglei, H. cambridgei, H. oregonensis, and Pellenes canadensis. Species tree analyses by ASTRAL and SVDQuartets gave almost completely congruent results. Several nodes in the ML phylogeny from 12.33 kb of mitochondrial data are incongruent with the nuclear phylogeny and indicate possible mitochondrial introgression: the internal relationships of the americanus and the coecatus groups, the relationship between the altanus, decorus, banksi, and americanus group, and between H. clypeatus and the coecatus group. To determine the relative contributions of ILS and introgression, we analyzed gene tree discordance for nuclear loci longer than 1 kb using Bayesian Concordance Analysis (BCA) for the americanus group (679 loci) and the VCCR clade (viridipes/clypeatus/coecatus/roberti groups) (517 loci) and found signals of introgression in both. Finally, we tested specifically for introgression in the concatenated nuclear matrix with Patterson's D statistics and DFOIL. We found nuclear introgression resulting in substantial admixture between americanus group species, between H. roberti and the clypeatus group, and between the clypeatus and coecatus groups.

CONCLUSIONS: Our results indicate that the phylogenetic history of Habronattus is predominantly a diverging tree, but that hybridization may have been common between phylogenetically distant species, especially in subgroups with complex courtship displays.}, } @article {pmid29471780, year = {2018}, author = {Carugo, O}, title = {How large B-factors can be in protein crystal structures.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {61}, pmid = {29471780}, issn = {1471-2105}, mesh = {Amino Acid Sequence ; Amino Acids/chemistry ; Crystallography, X-Ray ; Databases, Protein ; Models, Molecular ; Protein Conformation ; Proteins/*chemistry ; Solvents ; }, abstract = {BACKGROUND: Protein crystal structures are potentially over-interpreted since they are routinely refined without any restraint on the upper limit of atomic B-factors. Consequently, some of their atoms, undetected in the electron density maps, are allowed to reach extremely large B-factors, even above 100 square Angstroms, and their final positions are purely speculative and not based on any experimental evidence.

RESULTS: A strategy to define B-factors upper limits is described here, based on the analysis of protein crystal structures deposited in the Protein Data Bank prior 2008, when the tendency to allow B-factor to arbitrary inflate was limited. This B-factor upper limit (B_max) is determined by extrapolating the relationship between crystal structure average B-factor and percentage of crystal volume occupied by solvent (pcVol) to pcVol =100%, when, ab absurdo, the crystal contains only liquid solvent, the structure of which is, by definition, undetectable in electron density maps.

CONCLUSIONS: It is thus possible to highlight structures with average B-factors larger than B_max, which should be considered with caution by the users of the information deposited in the Protein Data Bank, in order to avoid scientifically deleterious over-interpretations.}, } @article {pmid29471481, year = {2018}, author = {Deveau, A and Bonito, G and Uehling, J and Paoletti, M and Becker, M and Bindschedler, S and Hacquard, S and Hervé, V and Labbé, J and Lastovetsky, OA and Mieszkin, S and Millet, LJ and Vajna, B and Junier, P and Bonfante, P and Krom, BP and Olsson, S and van Elsas, JD and Wick, LY}, title = {Bacterial-fungal interactions: ecology, mechanisms and challenges.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {335-352}, doi = {10.1093/femsre/fuy008}, pmid = {29471481}, issn = {1574-6976}, mesh = {Animals ; *Bacterial Physiological Phenomena ; Ecology ; Fungi/*physiology ; Microbial Interactions/*physiology ; }, abstract = {Fungi and bacteria are found living together in a wide variety of environments. Their interactions are significant drivers of many ecosystem functions and are important for the health of plants and animals. A large number of fungal and bacterial families engage in complex interactions that lead to critical behavioural shifts of the microorganisms ranging from mutualism to antagonism. The importance of bacterial-fungal interactions (BFI) in environmental science, medicine and biotechnology has led to the emergence of a dynamic and multidisciplinary research field that combines highly diverse approaches including molecular biology, genomics, geochemistry, chemical and microbial ecology, biophysics and ecological modelling. In this review, we discuss recent advances that underscore the roles of BFI across relevant habitats and ecosystems. A particular focus is placed on the understanding of BFI within complex microbial communities and in regard of the metaorganism concept. We also discuss recent discoveries that clarify the (molecular) mechanisms involved in bacterial-fungal relationships, and the contribution of new technologies to decipher generic principles of BFI in terms of physical associations and molecular dialogues. Finally, we discuss future directions for research in order to stimulate synergy within the BFI research area and to resolve outstanding questions.}, } @article {pmid29471451, year = {2018}, author = {Cahill, JA and Heintzman, PD and Harris, K and Teasdale, MD and Kapp, J and Soares, AER and Stirling, I and Bradley, D and Edwards, CJ and Graim, K and Kisleika, AA and Malev, AV and Monaghan, N and Green, RE and Shapiro, B}, title = {Genomic Evidence of Widespread Admixture from Polar Bears into Brown Bears during the Last Ice Age.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1120-1129}, doi = {10.1093/molbev/msy018}, pmid = {29471451}, issn = {1537-1719}, abstract = {Recent genomic analyses have provided substantial evidence for past periods of gene flow from polar bears (Ursus maritimus) into Alaskan brown bears (Ursus arctos), with some analyses suggesting a link between climate change and genomic introgression. However, because it has mainly been possible to sample bears from the present day, the timing, frequency, and evolutionary significance of this admixture remains unknown. Here, we analyze genomic DNA from three additional and geographically distinct brown bear populations, including two that lived temporally close to the peak of the last ice age. We find evidence of admixture in all three populations, suggesting that admixture between these species has been common in their recent evolutionary history. In addition, analyses of ten fossil bears from the now-extinct Irish population indicate that admixture peaked during the last ice age, whereas brown bear and polar bear ranges overlapped. Following this peak, the proportion of polar bear ancestry in Irish brown bears declined rapidly until their extinction. Our results support a model in which ice age climate change created geographically widespread conditions conducive to admixture between polar bears and brown bears, as is again occurring today. We postulate that this model will be informative for many admixing species pairs impacted by climate change. Our results highlight the power of paleogenomics to reveal patterns of evolutionary change that are otherwise masked in contemporary data.}, } @article {pmid29471361, year = {2018}, author = {Vuillemin, A and Ariztegui, D and Horn, F and Kallmeyer, J and Orsi, WD and , }, title = {Microbial community composition along a 50 000-year lacustrine sediment sequence.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, pmid = {29471361}, issn = {1574-6941}, abstract = {For decades, microbial community composition in subseafloor sediments has been the focus of extensive studies. In deep lacustrine sediments, however, the taxonomic composition of microbial communities remains undercharacterized. Greater knowledge on microbial diversity in lacustrine sediments would improve our understanding of how environmental factors, and resulting selective pressures, shape subsurface biospheres in marine and freshwater sediments. Using high-throughput sequencing of 16S rRNA genes across high-resolution climate intervals covering the last 50 000 years in Laguna Potrok Aike, Argentina, we identified changes in microbial populations in response to both past environmental conditions and geochemical changes of the sediment during burial. Microbial communities in Holocene sediments were most diverse, reflecting a layering of taxa linked to electron acceptors availability. In deeper intervals, the data show that salinity, organic matter and the depositional conditions over the Last Glacial-interglacial cycle were all selective pressures in the deep lacustrine assemblage resulting in a genetically distinct biosphere from the surface dominated primarily by Bathyarchaeota and Atribacteria groups. However, similar to marine sediments, some dominant taxa in the shallow subsurface persisted into the subsurface as minor fraction of the community. The subsequent establishment of a deep subsurface community likely results from a combination of paleoenvironmental factors that have shaped the pool of available substrates, together with substrate depletion and/or reworking of organic matter with depth.}, } @article {pmid29471354, year = {2018}, author = {Leonard, AFC and Yin, XL and Zhang, T and Hui, M and Gaze, WH}, title = {A coliform-targeted metagenomic method facilitating human exposure estimates to Escherichia coli-borne antibiotic resistance genes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy024}, pmid = {29471354}, issn = {1574-6941}, support = {WT097835MF//Wellcome Trust/United Kingdom ; WT101650MA//Wellcome Trust/United Kingdom ; MR/M008924/1//Medical Research Council/United Kingdom ; BB/K003240/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Antimicrobial resistance and the spread of antibiotic resistance genes (ARGs) pose a threat to human health. Community-acquired infections resistant to treatment with first-line antibiotics are increasing, and there are few studies investigating environmental exposures and transmission. Our objective is to develop a novel targeted metagenomic method to quantify the abundance and diversity of ARGs in a faecal indicator bacterium, and to estimate human exposure to resistant bacteria in a natural environment. Sequence data from Escherichia coli metagenomes from 13 bathing waters in England were analysed using the ARGs Online Analysis Pipeline to estimate the abundance and diversity of resistance determinants borne by this indicator bacterium. These data were averaged over the 13 sites and used along with data on the levels of E. coli in English bathing waters in 2016 and estimates of the volume of water that water users typically ingest in an average session of their chosen activityto quantify the numbers of ARGs that water users ingest. Escherichia coli in coastal bathing waters were found to harbour on average 1.24 ARGs per cell. Approximately 2.5 million water sports sessions occurred in England in 2016 that resulted in water users ingesting at least 100 E. coli-borne ARGs.}, } @article {pmid29471328, year = {2018}, author = {Morrow, KM and Tedford, AR and Pankey, MS and Lesser, MP}, title = {A member of the Roseobacter clade, Octadecabacter sp., is the dominant symbiont in the brittle star Amphipholis squamata.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy030}, pmid = {29471328}, issn = {1574-6941}, abstract = {Symbiotic associations with subcuticular bacteria (SCB) have been identified and studied in many echinoderms, including the SCB of the brooding brittle star, Amphipholis squamata. Previous studies on the SCB of A. squamata placed the isolated bacterium, designated as AS1, in the genus Vibrio (Gammaproteobacteria), but subsequent studies suggested that the SCB of echinoderms belong to the Alphaproteobacteria. This study examines the taxonomic composition of SCB associated with A. squamata from the Northwest Atlantic using the 16S rRNA gene and next generation sequencing. Results show the presence of a single dominant bacterial type, within the Roseobacter clade, family Rhodobacteraceae, which composes 70%-80% of the A. squamata microbiome. These Rhodobacteraceae sequences were identified as members of the genus Octadecabacter. Additionally, the original isolate, AS1, from the brittle star A. squamata also belongs in the genus Octadecabacter based on Sanger sequencing of cloned 16S rRNA gene sequences. By comparison, adjacent seawater and sediment porewater communities were significantly more diverse, hosting bacteria in the phyla Proteobacteria, Bacteroidetes, Cyanobacteria, Verrucomicrobia and Actinobacteria. Thus, a distinct SCB community is present in A. squamata that is dominated by a member of the genus Octadecabacter and is identical to the original isolate, AS1, from this brittle star.}, } @article {pmid29471079, year = {2018}, author = {Bell, CD and Gonzalez, LA}, title = {Exploring the utility of "next-generation" sequence data on inferring the phylogeny of the South American Valeriana (Valerianaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {44-49}, doi = {10.1016/j.ympev.2018.02.014}, pmid = {29471079}, issn = {1095-9513}, mesh = {Base Sequence ; Genetic Loci ; High-Throughput Nucleotide Sequencing/*methods ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; Software ; Species Specificity ; Valerian/*classification/*genetics ; }, abstract = {This study aimed to investigate the phylogenetic utility of genotyping-by-sequencing (GBS) data in the southern South American subclade of Valerianaceae (Dipsacales). The variety of forms that has arisen in this clade, presumably over the past 5-10 million years, has all the signatures of an adaptive and rapid radiation. While the phylogeny of Valerianaceae has received a great deal of attention in the last decade, species relationships have been hard to resolve using traditional phylogenetic markers. Here, we collected high-throughput genomic sequence data from reduced-representation libraries obtained through GBS protocols. Putative orthologs were identified using within- and among-sample clustering using the computer software pyRAD. We recovered over 3000 loci for 14 species of southern South AmericanValeriana,with 140 loci present across all samples.We analyzed a set of phylogenetic trees generated from each locus using maximum likelihood methods, as well as multispecies coalescent (∗BEAST) methods. For comparative purposes, we also used a supermatrix approach to infer the phylogeny for these taxa. Across different methods and data sets, we recovered consistent relationships for the southern South American valerians that we sampled with varying degrees of support.}, } @article {pmid29470955, year = {2018}, author = {Torroba, B and Herrera, A and Menendez, A and Pons, S}, title = {PI3K regulates intraepithelial cell positioning through Rho GTP-ases in the developing neural tube.}, journal = {Developmental biology}, volume = {436}, number = {1}, pages = {42-54}, doi = {10.1016/j.ydbio.2018.02.005}, pmid = {29470955}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation ; Cell Polarity/*genetics ; Cell Proliferation ; Chick Embryo ; Immunoblotting ; Immunohistochemistry ; In Situ Hybridization ; Neural Tube/embryology/*metabolism ; Neuroepithelial Cells/metabolism ; Neurogenesis/*genetics/physiology ; Phosphatidylinositol 3-Kinases/*metabolism ; Reverse Transcriptase Polymerase Chain Reaction ; Signal Transduction ; rho GTP-Binding Proteins/*metabolism ; }, abstract = {Phosphatidylinositol 3-kinases (PI3Ks) are signal transducers of many biological processes. Class 1 A PI3Ks are hetero dimers formed by a regulatory and a catalytic subunit. We have used the developing chicken neural tube (NT) to study the roles played by PI3K during the process of cell proliferation and differentiation. Notably, we have observed that in addition to its well characterized anti apoptotic activity, PI3K also plays a crucial role in intra epithelial cell positioning, and unlike its role in survival that mainly depends on AKT, the activity in cell positioning is mediated by Rho GTPase family members. Additionally, we have observed that activating mutations of PI3K that are remarkably frequent in many human cancers, cause an unrestrained basal migration of the neuroepithelial cells that end up breaking through the basal membrane invading the surrounding mesenchymal tissue. The mechanism described in this work contribute not only to acquire a greater knowledge of the intraepithelial cell positioning process, but also give new clues on how activating mutations of PI3K contribute to cell invasion during the first stages of tumour dissemination.}, } @article {pmid29470634, year = {2018}, author = {Terasaki, M and Miyagawa, S and Yamada, M and Nishida, H}, title = {Detection of Bacterial DNA During the Process of Sake Production Using Sokujo-Moto.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {874-879}, pmid = {29470634}, issn = {1432-0991}, mesh = {DNA, Bacterial/*genetics/isolation & purification ; Fermentation ; Food Contamination/analysis ; Food Microbiology ; Lactobacillus/isolation & purification/metabolism ; Oryza/classification/microbiology ; Wine/analysis/*microbiology ; }, abstract = {There are two types of starter cultures used in Japanese rice wine (sake) fermentation, namely, sokujo-moto and yamahai-moto. Analyses of microbiota changes during sake production using yamahai-moto have already been reported. In this study, we analyzed microbiota changes during sake production using sokujo-moto. In addition, we sequenced bacterial DNA from the water used in sake production. The Lactobacillus DNA sequences, which are frequently detected during sake production using yamahai-moto, were not detected during sake production using sokujo-moto, indicating that the Lactobacillus DNA detected in sakes made from yamahai-moto is from the fermentation starter. Most bacterial DNA sequences detected in water were not found in the production samples of sake suggesting that these bacteria do not proliferate during sake production. Thus, most of the bacterial DNA sequences detected during the production may be from the bacterial contamination during the production process.}, } @article {pmid29469939, year = {2018}, author = {Skwierzyńska, AM and Plesnar-Bielak, A}, title = {Proximate mechanisms of the differences in reproductive success of males bearing different alleles of Pgdh - a gene involved in a sexual conflict in bulb mite.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {657-664}, doi = {10.1111/jeb.13250}, pmid = {29469939}, issn = {1420-9101}, abstract = {Enzyme polymorphism in phosphogluconate dehydrogenase (Pgdh) is a striking example of single gene polymorphism involved in sexual conflict in bulb mite Rhizoglyphus robini. Males homozygous for the S Pgdh allele were shown to achieve higher reproductive success than FF homozygous males, while negatively influencing fecundity of their female partners. Here, we investigate proximate mechanisms responsible for the increased reproductive success of SS males and find that the S allele is associated with shorter time until copulation, higher copulation frequency and increased sperm production. We also show that Pgdh alleles are probably codominant, with SS males gaining the highest reproductive success, FF males - the lowest - and FS-heterozygous males taking an intermediate position in all fitness parameters differentiating males of different genotypes. Additionally, we confirm the negative effect that S-bearing males impose on the fecundity of females they mate with, showing a clear pattern of interlocus sexual conflict. We discuss that this effect is probably associated with increased copulation frequency. Whereas, contrary to what we have predicted, the S allele does not cause increased general male mobility, we speculate that the S allele-bearing males are more efficient in forcing copulation and/or detecting females.}, } @article {pmid29469691, year = {2018}, author = {Kim, YO and Park, IS and Park, S and Nam, BH and Kim, DG and Won, SM and Yoon, JH}, title = {Paracoccus alimentarius sp. nov., isolated from a Korean foodstuff, salted pollack.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1238-1243}, doi = {10.1099/ijsem.0.002658}, pmid = {29469691}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Paracoccus/*classification/genetics/isolation & purification ; Phosphatidylcholines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seafood/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and coccoid or ovoid bacterial strain, designated LB2T, was isolated from a Korean foodstuff, salted pollack. Strain LB2T grew optimally at 25-30 °C, at pH 7.0-8.0 and in the presence of 0-2.0 % (w/v) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain LB2T belonged to the genus Paracoccus, coherently clustering with the type strain of Paracoccus sulfuroxidans. Strain LB2T exhibited 16S rRNA gene sequence similarity values of 98.0 and 97.0 % to the type strains of P. sulfuroxidans and Paracoccus halophilus, respectively, and of less than 96.9 % to the type strains of other Paracoccus species. Strain LB2T contained Q-10 as the predominant ubiquinone. Major fatty acids of strain LB2T were cyclo C19 : 0ω8c, C18 : 1ω7c and C16 : 0 (when grown on MA) or C18 : 1ω7c and C16 : 0 (on TSA). The major polar lipids detected in strain LB2T were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, one unidentified aminolipid and one unidentified glycolipid. The DNA G+C content of strain LB2T was 61.4 mol% and its DNA-DNA relatedness values with the type strains of P. sulfuroxidans and P. halophilus were 26 and 18 %, respectively. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain LB2T is separated from recognized Paracoccus species. On the basis of the data presented, strain LB2T is considered to represent a novel species of the genus Paracoccus, for which the name Paracoccus alimentarius sp. nov. is proposed. The type strain is LB2T (=KCTC 62138T=NBRC 113023T).}, } @article {pmid29469688, year = {2018}, author = {Kim, YO and Park, IS and Park, S and Nam, BH and Kim, DG and Choi, SG and Bae, JW and Yoon, JH}, title = {Bizionia berychis sp. nov., isolated from intestinal tract of a splendid alfonsino (Beryx splendens).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1227-1232}, doi = {10.1099/ijsem.0.002656}, pmid = {29469688}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fishes/*microbiology ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Intestines/*microbiology ; Nucleic Acid Hybridization ; Pacific Ocean ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-motile, aerobic and rod-shaped bacterial strain, designated RA3-3-1T, was isolated from splendid alfonsino (Beryxsplendens) collected from the North Pacific Ocean. Strain RA3-3-1T grew optimally at 25 °C, at pH 7.0-8.0 and in the presence of 1.0-3.0 % (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain RA3-3-1T belonged to the genus Bizionia, clustering with the type strain of Bizionia fulviae. Strain RA3-3-1T exhibited 16S rRNA gene sequence similarities of 98.7, 97.6 and 97.3 % to the type strains of B. fulviae, Bizionia paragorgiae and Bizionia saleffrena, respectively, and of 95.5-96.4 % to the type strains of the other Bizionia species. Strain RA3-3-1T contained MK-6 as the predominant menaquinone and anteiso-C15 : 0, iso-C16 : 0 3-OH, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C17 : 0 3-OH, iso-C15 : 0 and C17 : 0 2-OH as the major fatty acids. The major polar lipids detected in strain RA3-3-1T were phosphatidylethanolamine, one unidentified lipid and one unidentified aminolipid. The DNA G+C content of strain RA3-3-1T was 34.1 mol% and its DNA-DNA relatedness values with the type strains of B. fulviae, B. paragorgiae and B. saleffrena were 12-29 %. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain RA3-3-1T is separate from recognized species of the genus Bizionia. On the basis of the data presented, strain RA3-3-1T is considered to represent a novel species of the genus Bizionia, for which the name Bizionia berychis sp. nov. is proposed. The type strain is RA3-3-1T (=KCTC 62140T=NBRC 113024T).}, } @article {pmid29469135, year = {2018}, author = {Gertler, P and Galiani, S and Romero, M}, title = {How to make replication the norm.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {417-419}, doi = {10.1038/d41586-018-02108-9}, pmid = {29469135}, issn = {1476-4687}, } @article {pmid29469134, year = {2018}, author = {Jan, YN and Jan, LY}, title = {Force-activated ion channels in close-up.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {469-470}, doi = {10.1038/d41586-018-01631-z}, pmid = {29469134}, issn = {1476-4687}, mesh = {*Ion Channel Gating ; *Ion Channels ; }, } @article {pmid29469133, year = {2018}, author = {}, title = {Why current negative-emissions strategies remain 'magical thinking'.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {404}, doi = {10.1038/d41586-018-02184-x}, pmid = {29469133}, issn = {1476-4687}, } @article {pmid29469132, year = {2018}, author = {}, title = {Orangutan losses, brain-injury test and Grace Mugabe's PhD.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {408-409}, doi = {10.1038/d41586-018-02098-8}, pmid = {29469132}, issn = {1476-4687}, } @article {pmid29469131, year = {2018}, author = {Tollefson, J}, title = {Ocean-wide sensor array provides new look at global ocean current.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {413-414}, doi = {10.1038/d41586-018-02113-y}, pmid = {29469131}, issn = {1476-4687}, } @article {pmid29469130, year = {2018}, author = {Murtaugh, LC and MacDonald, RJ}, title = {An inflammatory transcriptional switch.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {470-472}, doi = {10.1038/d41586-018-01262-4}, pmid = {29469130}, issn = {1476-4687}, mesh = {*Recombination, Genetic ; *Transcription, Genetic ; }, } @article {pmid29469129, year = {2018}, author = {Hornburg, D}, title = {Authorship position should not serve as a proxy metric.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {423}, doi = {10.1038/d41586-018-02204-w}, pmid = {29469129}, issn = {1476-4687}, mesh = {*Authorship ; *Bibliometrics ; Publishing ; }, } @article {pmid29469128, year = {2018}, author = {James, SL}, title = {Molecules pressured to react.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {468-469}, doi = {10.1038/d41586-018-02047-5}, pmid = {29469128}, issn = {1476-4687}, } @article {pmid29469127, year = {2018}, author = {Ledford, H}, title = {Who exactly counts as an adolescent?.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {429-431}, doi = {10.1038/d41586-018-02169-w}, pmid = {29469127}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Behavior ; *Adolescent Development ; Adolescent Nutritional Physiological Phenomena ; Adult ; Age Factors ; Aged, 80 and over ; Aging/physiology/psychology ; Child ; Female ; History, 20th Century ; Hormones/metabolism ; Humans ; London ; Male ; Marriage/statistics & numerical data ; Menarche/physiology/psychology ; Neurosciences/*trends ; Puberty/*physiology/*psychology ; Sexual Maturation/physiology ; Social Sciences/trends ; Time Factors ; Young Adult ; }, } @article {pmid29469126, year = {2018}, author = {Vetterlein, D and Schlüter, S and Vogel, HJ}, title = {Root systems offer insight into better soils.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {423}, doi = {10.1038/d41586-018-02202-y}, pmid = {29469126}, issn = {1476-4687}, mesh = {Plant Roots/*chemistry ; *Soil ; Soil Pollutants/analysis ; }, } @article {pmid29469125, year = {2018}, author = {Johnson, MB and Stevens, B}, title = {Pruning hypothesis comes of age.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {438-439}, doi = {10.1038/d41586-018-02053-7}, pmid = {29469125}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Development ; Adult ; Age of Onset ; Aged ; Aged, 80 and over ; Animals ; Brain/cytology/*growth & development/immunology/physiology ; Cell Count ; Child ; Child, Preschool ; Complement C4/genetics/immunology ; Dendritic Spines/metabolism ; Disease Models, Animal ; Electroencephalography ; Frontal Lobe/cytology/growth & development/physiology/physiopathology ; Genetic Predisposition to Disease ; History, 20th Century ; History, 21st Century ; Humans ; Infant ; Infant, Newborn ; Mice ; Middle Aged ; *Models, Neurological ; *Neuronal Plasticity/genetics/immunology ; Neurosciences/history ; Schizophrenia/genetics/pathology/*physiopathology ; Sleep/*physiology ; Synapses/immunology/*metabolism ; Young Adult ; }, } @article {pmid29469123, year = {2018}, author = {Brönnimann, S and Wintzer, J}, title = {Use imprint of society and history on climate data to inform climate services.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {423}, doi = {10.1038/d41586-018-02201-z}, pmid = {29469123}, issn = {1476-4687}, mesh = {Climate Change/*statistics & numerical data ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Policy Making ; *Records ; Social Change/*history ; }, } @article {pmid29469122, year = {2018}, author = {Gibney, E}, title = {Physicists plan antimatter's first outing - in a van.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {412-413}, doi = {10.1038/d41586-018-02221-9}, pmid = {29469122}, issn = {1476-4687}, } @article {pmid29469120, year = {2018}, author = {Rochmyaningsih, D}, title = {Indonesian scientists hamstrung by year-long funding delay.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {415-416}, doi = {10.1038/d41586-018-02118-7}, pmid = {29469120}, issn = {1476-4687}, mesh = {Budgets ; Federal Government ; Financing, Organized/economics ; Humans ; Indonesia ; Research/*economics ; Research Personnel/*economics ; *Research Support as Topic/economics ; Time Factors ; }, } @article {pmid29469119, year = {2018}, author = {Abbott, A}, title = {Italian election leaves science out in the cold.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {411-412}, doi = {10.1038/d41586-018-02223-7}, pmid = {29469119}, issn = {1476-4687}, mesh = {Animals ; Budgets/legislation & jurisprudence ; *Federal Government ; Humans ; Italy ; *Politics ; Research Personnel/economics/psychology ; Research Support as Topic/legislation & jurisprudence ; Science/*economics/*legislation & jurisprudence/trends ; }, } @article {pmid29469118, year = {2018}, author = {}, title = {Science needs to redefine excellence.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {403-404}, doi = {10.1038/d41586-018-02183-y}, pmid = {29469118}, issn = {1476-4687}, mesh = {Consensus ; European Union ; Journal Impact Factor ; *Program Evaluation ; *Public Policy ; Reproducibility of Results ; Research Personnel/psychology ; Research Support as Topic/organization & administration ; Science/economics/*standards ; Social Change ; }, } @article {pmid29469117, year = {2018}, author = {Blum, R and Boyden, J}, title = {Understand the lives of youth in low-income countries.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {435-437}, doi = {10.1038/d41586-018-02107-w}, pmid = {29469117}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Behavior ; *Adolescent Health ; Child ; Child Nutritional Physiological Phenomena ; Developed Countries/statistics & numerical data ; Developing Countries/*economics/statistics & numerical data ; Employment/statistics & numerical data ; Female ; Humans ; *Income/statistics & numerical data ; Infant ; Literacy/statistics & numerical data ; Male ; Minority Groups/psychology/statistics & numerical data ; Poverty/psychology/statistics & numerical data ; Pregnancy ; Risk-Taking ; Sex Factors ; Social Marginalization/psychology ; Stress, Psychological/epidemiology ; Vulnerable Populations/psychology/statistics & numerical data ; Young Adult ; }, } @article {pmid29469116, year = {2018}, author = {Woolston, C}, title = {Teen spirit in the lab.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {559-561}, doi = {10.1038/d41586-018-02176-x}, pmid = {29469116}, issn = {1476-4687}, mesh = {Adolescent ; Age Factors ; Community-Institutional Relations ; Humans ; *Laboratories ; *Mentoring ; Microscopy, Fluorescence, Multiphoton ; Motivation ; Research/*education ; Research Personnel/education/psychology ; Safety ; Students/*psychology ; Workforce ; }, } @article {pmid29469114, year = {2018}, author = {}, title = {Coming of age.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {425}, doi = {10.1038/d41586-018-02168-x}, pmid = {29469114}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Behavior ; *Adolescent Development ; *Adolescent Health ; Adult ; Behavioral Research/*trends ; Child ; Developing Countries ; Humans ; Puberty/*physiology/*psychology ; Young Adult ; }, } @article {pmid29469113, year = {2018}, author = {Li, D and Liang, X}, title = {Neurons mimicked by electronics.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {472-473}, doi = {10.1038/d41586-018-02025-x}, pmid = {29469113}, issn = {1476-4687}, mesh = {Electronics ; *Nerve Net ; *Neurons ; }, } @article {pmid29469112, year = {2018}, author = {Smith, K}, title = {Sex and drugs and self-control: how the teen brain navigates risk.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {426-428}, doi = {10.1038/d41586-018-02170-3}, pmid = {29469112}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Behavior ; Adolescent Health ; Adult ; Brain/growth & development/*physiology ; Cause of Death ; Child ; Cognition/physiology ; Female ; Friends/psychology ; Health Behavior ; Humans ; Impulsive Behavior ; Male ; Peer Influence ; Reward ; Risk Assessment ; *Risk-Taking ; Sedentary Behavior ; Self-Control/*psychology ; Sexual Behavior/*psychology ; Substance-Related Disorders/*psychology ; Ventral Striatum/physiology ; Young Adult ; }, } @article {pmid29469111, year = {2018}, author = {}, title = {Correction.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {416}, doi = {10.1038/d41586-018-02164-1}, pmid = {29469111}, issn = {1476-4687}, } @article {pmid29469110, year = {2018}, author = {Ledford, H}, title = {CRISPR hack transforms cells into data recorders.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {414-415}, doi = {10.1038/d41586-018-02068-0}, pmid = {29469110}, issn = {1476-4687}, mesh = {*Cell Count ; *Clustered Regularly Interspaced Short Palindromic Repeats ; }, } @article {pmid29469109, year = {2018}, author = {Abedalthagafi, M}, title = {As a Saudi woman scientist, I'm tired of negative stereotypes.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {405}, doi = {10.1038/d41586-018-02163-2}, pmid = {29469109}, issn = {1476-4687}, mesh = {Child, Preschool ; Developed Countries ; *Developing Countries ; Female ; Humans ; Male ; Research Personnel/*psychology ; Saudi Arabia ; Sex Factors ; Sexism/*psychology ; *Stereotyping ; United States ; Women/*psychology ; }, } @article {pmid29469108, year = {2018}, author = {Odgers, C}, title = {Smartphones are bad for some teens, not all.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {432-434}, pmid = {29469108}, issn = {1476-4687}, support = {P30 DA023026/DA/NIDA NIH HHS/United States ; }, mesh = {Adolescent ; *Adolescent Behavior ; Adolescent Health/*statistics & numerical data/trends ; Adult ; Age Factors ; Child ; Europe ; Family Relations/psychology ; Female ; Friends/psychology ; Humans ; Interpersonal Relations ; Male ; Mental Health/*statistics & numerical data/trends ; Pregnancy ; *Problem Behavior ; Safety ; Smartphone/*statistics & numerical data ; *Social Behavior ; Social Class ; Social Media/*statistics & numerical data ; Suicide/statistics & numerical data/trends ; Time Factors ; United States ; Vulnerable Populations/psychology/statistics & numerical data ; Young Adult ; }, } @article {pmid29469107, year = {2018}, author = {Webb, S}, title = {Deep learning for biology.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {555-557}, doi = {10.1038/d41586-018-02174-z}, pmid = {29469107}, issn = {1476-4687}, mesh = {Animals ; Biology/*methods ; Diagnostic Imaging/methods ; Drug Discovery/methods ; Electronic Health Records ; Genomics/methods ; Humans ; Image Interpretation, Computer-Assisted/*methods ; *Machine Learning ; Microscopy ; Neural Networks (Computer) ; Plants/genetics ; Polymorphism, Single Nucleotide/genetics ; Quality Control ; Robotics ; Rodentia ; Software ; }, } @article {pmid29469106, year = {2018}, author = {}, title = {Correction.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {419}, doi = {10.1038/d41586-018-02166-z}, pmid = {29469106}, issn = {1476-4687}, } @article {pmid29469105, year = {2018}, author = {Oschlies, A}, title = {Solar geoengineering must take temperature debt into account.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {423}, doi = {10.1038/d41586-018-02203-x}, pmid = {29469105}, issn = {1476-4687}, mesh = {Greenhouse Effect ; *Sunlight ; *Temperature ; }, } @article {pmid29469104, year = {2018}, author = {}, title = {Race- and gender-based bias persists in US science.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {561}, doi = {10.1038/d41586-018-02175-y}, pmid = {29469104}, issn = {1476-4687}, mesh = {Adult ; African Americans/psychology/statistics & numerical data ; Engineering ; Female ; Humans ; Male ; Mathematics ; Minority Groups/psychology/statistics & numerical data ; Racism/*statistics & numerical data ; *Research ; Research Personnel/*psychology/*statistics & numerical data ; Science ; Sex Distribution ; Sexism/*statistics & numerical data ; Sexual Harassment ; Surveys and Questionnaires ; Technology ; United States ; Workforce ; }, } @article {pmid29469102, year = {2018}, author = {}, title = {Adolescence research must grow up.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {403}, doi = {10.1038/d41586-018-02185-w}, pmid = {29469102}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Behavior ; *Adolescent Development ; *Adolescent Health ; Aged ; Behavioral Research/*trends ; Biomedical Research/*trends ; Child ; HIV Infections ; Health Policy/trends ; Humans ; Infant ; Mental Health ; Young Adult ; }, } @article {pmid29469101, year = {2018}, author = {}, title = {Correction.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {423}, doi = {10.1038/d41586-018-02205-9}, pmid = {29469101}, issn = {1476-4687}, } @article {pmid29469099, year = {2018}, author = {Worthman, CM and Trang, K}, title = {Dynamics of body time, social time and life history at adolescence.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {451-457}, pmid = {29469099}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Development ; *Adolescent Health/trends ; Body Height ; *Culture ; Education/history/trends ; Female ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Humans ; Learning/physiology ; Life Style ; Male ; Menarche/physiology ; Puberty/*physiology/*psychology ; *Social Change ; Time Factors ; }, abstract = {Recent opposing trends towards earlier physical maturation and later social maturation present a conundrum of apparent biological-social mismatch. Here we use life history analysis from evolutionary ecology to identify forces that drive these shifts. Together with findings in developmental science, our life history analysis indicates that adolescence is a distinctive period for biological embedding of culture. Ethnographic evidence shows that mass education is a novel feature of the globalizing cultural configurations of adolescence, which are driven by transformations in labour, livelihood and lifestyle. Evaluation of the life history trade-offs and sociocultural ecologies that are experienced by adolescents may offer a practical basis for enhancing their development.}, } @article {pmid29469098, year = {2018}, author = {van Gestel, N and Shi, Z and van Groenigen, KJ and Osenberg, CW and Andresen, LC and Dukes, JS and Hovenden, MJ and Luo, Y and Michelsen, A and Pendall, E and Reich, PB and Schuur, EAG and Hungate, BA}, title = {Predicting soil carbon loss with warming.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {E4-E5}, pmid = {29469098}, issn = {1476-4687}, } @article {pmid29469097, year = {2018}, author = {Bersten, MC and Folatelli, G and García, F and Van Dyk, SD and Benvenuto, OG and Orellana, M and Buso, V and Sánchez, JL and Tanaka, M and Maeda, K and Filippenko, AV and Zheng, W and Brink, TG and Cenko, SB and de Jaeger, T and Kumar, S and Moriya, TJ and Nomoto, K and Perley, DA and Shivvers, I and Smith, N}, title = {A surge of light at the birth of a supernova.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {497-499}, pmid = {29469097}, issn = {1476-4687}, abstract = {It is difficult to establish the properties of massive stars that explode as supernovae. The electromagnetic emission during the first minutes to hours after the emergence of the shock from the stellar surface conveys important information about the final evolution and structure of the exploding star. However, the unpredictable nature of supernova events hinders the detection of this brief initial phase. Here we report the serendipitous discovery of a newly born, normal type IIb supernova (SN 2016gkg), which reveals a rapid brightening at optical wavelengths of about 40 magnitudes per day. The very frequent sampling of the observations allowed us to study in detail the outermost structure of the progenitor of the supernova and the physics of the emergence of the shock. We develop hydrodynamical models of the explosion that naturally account for the complete evolution of the supernova over distinct phases regulated by different physical processes. This result suggests that it is appropriate to decouple the treatment of the shock propagation from the unknown mechanism that triggers the explosion.}, } @article {pmid29469096, year = {2018}, author = {Yamamoto, K and Li, J and Garber, JAO and Rolfes, JD and Boursalian, GB and Borghs, JC and Genicot, C and Jacq, J and van Gastel, M and Neese, F and Ritter, T}, title = {Palladium-catalysed electrophilic aromatic C-H fluorination.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {511-514}, pmid = {29469096}, issn = {1476-4687}, mesh = {Blood-Brain Barrier ; Carbon/*chemistry ; Catalysis ; Fluorine/*chemistry ; *Halogenation ; Hydrogen/*chemistry ; Indicators and Reagents/chemistry ; Palladium/*chemistry ; Pharmaceutical Preparations/chemistry ; }, abstract = {Aryl fluorides are widely used in the pharmaceutical and agrochemical industries, and recent advances have enabled their synthesis through the conversion of various functional groups. However, there is a lack of general methods for direct aromatic carbon-hydrogen (C-H) fluorination. Conventional methods require the use of either strong fluorinating reagents, which are often unselective and difficult to handle, such as elemental fluorine, or less reactive reagents that attack only the most activated arenes, which reduces the substrate scope. A method for the direct fluorination of aromatic C-H bonds could facilitate access to fluorinated derivatives of functional molecules that would otherwise be difficult to produce. For example, drug candidates with improved properties, such as increased metabolic stability or better blood-brain-barrier penetration, may become available. Here we describe an approach to catalysis and the resulting development of an undirected, palladium-catalysed method for aromatic C-H fluorination using mild electrophilic fluorinating reagents. The reaction involves a mode of catalysis that is unusual in aromatic C-H functionalization because no organometallic intermediate is formed; instead, a reactive transition-metal-fluoride electrophile is generated catalytically for the fluorination of arenes that do not otherwise react with mild fluorinating reagents. The scope and functional-group tolerance of this reaction could provide access to functional fluorinated molecules in pharmaceutical and agrochemical development that would otherwise not be readily accessible.}, } @article {pmid29469095, year = {2018}, author = {Patton, GC and Olsson, CA and Skirbekk, V and Saffery, R and Wlodek, ME and Azzopardi, PS and Stonawski, M and Rasmussen, B and Spry, E and Francis, K and Bhutta, ZA and Kassebaum, NJ and Mokdad, AH and Murray, CJL and Prentice, AM and Reavley, N and Sheehan, P and Sweeny, K and Viner, RM and Sawyer, SM}, title = {Adolescence and the next generation.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {458-466}, pmid = {29469095}, issn = {1476-4687}, support = {MC_EX_MR/M01424X/1//Medical Research Council/United Kingdom ; MC_U123292701//Medical Research Council/United Kingdom ; }, mesh = {Adolescent ; *Adolescent Behavior/physiology/psychology ; Adolescent Development/*physiology ; *Adolescent Health/statistics & numerical data ; Adult ; Animals ; Child ; Cohort Studies ; Epigenesis, Genetic ; Female ; Gametogenesis ; Gene-Environment Interaction ; Germ Cells/physiology ; Housing ; Humans ; Income ; Infant, Newborn ; Infant, Small for Gestational Age ; Male ; Malnutrition/epidemiology ; Maternal Age ; *Maternal Exposure ; Menarche ; *Parents ; Paternal Age ; *Paternal Exposure ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Puberty/physiology/psychology ; Young Adult ; }, abstract = {Adolescent growth and social development shape the early development of offspring from preconception through to the post-partum period through distinct processes in males and females. At a time of great change in the forces shaping adolescence, including the timing of parenthood, investments in today's adolescents, the largest cohort in human history, will yield great dividends for future generations.}, } @article {pmid29469094, year = {2018}, author = {Dahl, RE and Allen, NB and Wilbrecht, L and Suleiman, AB}, title = {Importance of investing in adolescence from a developmental science perspective.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {441-450}, pmid = {29469094}, issn = {1476-4687}, mesh = {Adolescent ; *Adolescent Behavior ; *Adolescent Development ; *Adolescent Health ; Animals ; Behavioral Research/*trends ; Brain/growth & development/physiology ; Health Policy ; Humans ; Learning/physiology ; Models, Animal ; Puberty/physiology ; Sexual Maturation/physiology ; }, abstract = {This review summarizes the case for investing in adolescence as a period of rapid growth, learning, adaptation, and formational neurobiological development. Adolescence is a dynamic maturational period during which young lives can pivot rapidly-in both negative and positive directions. Scientific progress in understanding adolescent development provides actionable insights into windows of opportunity during which policies can have a positive impact on developmental trajectories relating to health, education, and social and economic success. Given current global changes and challenges that affect adolescents, there is a compelling need to leverage these advances in developmental science to inform strategic investments in adolescent health.}, } @article {pmid29469093, year = {2018}, author = {Sangwan, VK and Lee, HS and Bergeron, H and Balla, I and Beck, ME and Chen, KS and Hersam, MC}, title = {Multi-terminal memtransistors from polycrystalline monolayer molybdenum disulfide.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {500-504}, pmid = {29469093}, issn = {1476-4687}, abstract = {Memristors are two-terminal passive circuit elements that have been developed for use in non-volatile resistive random-access memory and may also be useful in neuromorphic computing. Memristors have higher endurance and faster read/write times than flash memory and can provide multi-bit data storage. However, although two-terminal memristors have demonstrated capacity for basic neural functions, synapses in the human brain outnumber neurons by more than a thousandfold, which implies that multi-terminal memristors are needed to perform complex functions such as heterosynaptic plasticity. Previous attempts to move beyond two-terminal memristors, such as the three-terminal Widrow-Hoff memristor and field-effect transistors with nanoionic gates or floating gates, did not achieve memristive switching in the transistor. Here we report the experimental realization of a multi-terminal hybrid memristor and transistor (that is, a memtransistor) using polycrystalline monolayer molybdenum disulfide (MoS2) in a scalable fabrication process. The two-dimensional MoS2 memtransistors show gate tunability in individual resistance states by four orders of magnitude, as well as large switching ratios, high cycling endurance and long-term retention of states. In addition to conventional neural learning behaviour of long-term potentiation/depression, six-terminal MoS2 memtransistors have gate-tunable heterosynaptic functionality, which is not achievable using two-terminal memristors. For example, the conductance between a pair of floating electrodes (pre- and post-synaptic neurons) is varied by a factor of about ten by applying voltage pulses to modulatory terminals. In situ scanning probe microscopy, cryogenic charge transport measurements and device modelling reveal that the bias-induced motion of MoS2 defects drives resistive switching by dynamically varying Schottky barrier heights. Overall, the seamless integration of a memristor and transistor into one multi-terminal device could enable complex neuromorphic learning and the study of the physics of defect kinetics in two-dimensional materials.}, } @article {pmid29469092, year = {2018}, author = {Zhao, Q and Zhou, H and Chi, S and Wang, Y and Wang, J and Geng, J and Wu, K and Liu, W and Zhang, T and Dong, MQ and Wang, J and Li, X and Xiao, B}, title = {Structure and mechanogating mechanism of the Piezo1 channel.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {487-492}, pmid = {29469092}, issn = {1476-4687}, mesh = {Animals ; *Cryoelectron Microscopy ; *Ion Channel Gating ; Ion Channels/chemistry/*metabolism/*ultrastructure ; *Mechanotransduction, Cellular ; Mice ; Models, Molecular ; Movement ; Structure-Activity Relationship ; }, abstract = {The mechanosensitive Piezo channels function as key eukaryotic mechanotransducers. However, their structures and mechanogating mechanisms remain unknown. Here we determine the three-bladed, propeller-like electron cryo-microscopy structure of mouse Piezo1 and functionally reveal its mechanotransduction components. Despite the lack of sequence repetition, we identify nine repetitive units consisting of four transmembrane helices each-which we term transmembrane helical units (THUs)-which assemble into a highly curved blade-like structure. The last transmembrane helix encloses a hydrophobic pore, followed by three intracellular fenestration sites and side portals that contain pore-property-determining residues. The central region forms a 90 Å-long intracellular beam-like structure, which undergoes a lever-like motion to connect THUs to the pore via the interfaces of the C-terminal domain, the anchor-resembling domain and the outer helix. Deleting extracellular loops in the distal THUs or mutating single residues in the beam impairs the mechanical activation of Piezo1. Overall, Piezo1 possesses a unique 38-transmembrane-helix topology and designated mechanotransduction components, which enable a lever-like mechanogating mechanism.}, } @article {pmid29469091, year = {2018}, author = {Crowther, TW and Machmuller, MB and Carey, JC and Allison, SD and Blair, JM and Bridgham, SD and Burton, AJ and Dijkstra, FA and Elberling, B and Estiarte, M and Larsen, KS and Laudon, H and Lupascu, M and Marhan, S and Mohan, J and Niu, S and J Peñuelas, J and Schmidt, IK and Templer, PH and Kröel-Dulay, G and Frey, S and Bradford, MA}, title = {Crowther et al. reply.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {E7-E8}, pmid = {29469091}, issn = {1476-4687}, } @article {pmid29469090, year = {2018}, author = {Yan, H and Yang, F and Pan, D and Lin, Y and Hohman, JN and Solis-Ibarra, D and Li, FH and Dahl, JEP and Carlson, RMK and Tkachenko, BA and Fokin, AA and Schreiner, PR and Galli, G and Mao, WL and Shen, ZX and Melosh, NA}, title = {Sterically controlled mechanochemistry under hydrostatic pressure.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {505-510}, pmid = {29469090}, issn = {1476-4687}, abstract = {Mechanical stimuli can modify the energy landscape of chemical reactions and enable reaction pathways, offering a synthetic strategy that complements conventional chemistry. These mechanochemical mechanisms have been studied extensively in one-dimensional polymers under tensile stress using ring-opening and reorganization, polymer unzipping and disulfide reduction as model reactions. In these systems, the pulling force stretches chemical bonds, initiating the reaction. Additionally, it has been shown that forces orthogonal to the chemical bonds can alter the rate of bond dissociation. However, these bond activation mechanisms have not been possible under isotropic, compressive stress (that is, hydrostatic pressure). Here we show that mechanochemistry through isotropic compression is possible by molecularly engineering structures that can translate macroscopic isotropic stress into molecular-level anisotropic strain. We engineer molecules with mechanically heterogeneous components-a compressible ('soft') mechanophore and incompressible ('hard') ligands. In these 'molecular anvils', isotropic stress leads to relative motions of the rigid ligands, anisotropically deforming the compressible mechanophore and activating bonds. Conversely, rigid ligands in steric contact impede relative motion, blocking reactivity. We combine experiments and computations to demonstrate hydrostatic-pressure-driven redox reactions in metal-organic chalcogenides that incorporate molecular elements that have heterogeneous compressibility, in which bending of bond angles or shearing of adjacent chains activates the metal-chalcogen bonds, leading to the formation of the elemental metal. These results reveal an unexplored reaction mechanism and suggest possible strategies for high-specificity mechanosynthesis.}, } @article {pmid29468839, year = {2018}, author = {Rübsam, H and Kirsch, F and Reimann, V and Erban, A and Kopka, J and Hagemann, M and Hess, WR and Klähn, S}, title = {The iron-stress activated RNA 1 (IsaR1) coordinates osmotic acclimation and iron starvation responses in the cyanobacterium Synechocystis sp. PCC 6803.}, journal = {Environmental microbiology}, volume = {20}, number = {8}, pages = {2757-2768}, doi = {10.1111/1462-2920.14079}, pmid = {29468839}, issn = {1462-2920}, abstract = {In nature, microorganisms are exposed to multiple stress factors in parallel. Here, we investigated the response of the model cyanobacterium Synechocystis sp. PCC 6803 to simultaneous iron limitation and osmotic stresses. Iron is a major limiting factor for bacterial and phytoplankton growth in most environments. Thus, bacterial iron homeostasis is tightly regulated. In Synechocystis, it is mediated mainly by the transcriptional regulator FurA and the iron-stress activated RNA 1 (IsaR1). IsaR1 is an important riboregulator that affects the acclimation of the photosynthetic apparatus to iron starvation in multiple ways. Upon increases in salinity, Synechocystis responds by accumulating the compatible solute glucosylglycerol (GG). We show that IsaR1 overexpression causes a reduction in the de novo GG synthesis rate upon salt shock. We verified the direct interaction between IsaR1 and the 5'UTR of the ggpS mRNA, which in turn drastically reduced the de novo synthesis of the key enzyme for GG synthesis, glucosylglycerol phosphate synthase (GgpS). Thus, IsaR1 specifically interferes with the salt acclimation process in Synechocystis, in addition to its primary regulatory function. Moreover, the salt-stimulated GgpS production became reduced under parallel iron limitation in WT - an effect which is, however, attenuated in an isaR1 deletion strain. Hence, IsaR1 is involved in the integration of the responses to different environmental perturbations and slows the osmotic adaptation process in cells suffering from parallel iron starvation.}, } @article {pmid29468831, year = {2018}, author = {Hackett, S and Ruxton, GD}, title = {The evolutionary stability of attenuators that mask information about animals that social partners can exploit.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {675-686}, doi = {10.1111/jeb.13253}, pmid = {29468831}, issn = {1420-9101}, abstract = {Signals and cues are fundamental to social interactions. A well-established concept in the study of animal communication is an amplifier, defined as a trait that does not add extra information to that already present in the original cue or signal, but rather enhances the fidelity with which variation in the original cue or signal is correctly perceived. Attenuators as the logical compliment of amplifiers: attenuators act to reduce the fidelity with which variation in a signal or cue can be reliably evaluated by the perceivers. Where amplifiers reduce the effect of noise on the perception of variation, attenuators add noise. Attenuators have been subject to much less consideration than amplifiers; however, they will be the focus of our theoretical study. We utilize an extension of a well-established model incorporated signal or cue inaccuracy and costly investments by emitter and perceiver in sending and attending to the signal or cue. We present broad conditions involving some conflict of interest between emitter and perceiver where it may be advantageous for emitters to invest in costly attenuators to mask cues from potential perceivers, and a subset of these conditions where the perceiver may be willing to invest in costly anti-attenuators to mitigate the loss of information to them. We demonstrate that attenuators can be evolutionary stable even if they are costly, even if they are sometimes disadvantageous and even if a perceiver can mount counter-measures to them. As such, we feel that attenuators of cues may be deserving of much more research attention.}, } @article {pmid29468804, year = {2018}, author = {Zhu, XM and Liang, S and Shi, HB and Lu, JP and Dong, B and Liao, QS and Lin, FC and Liu, XH}, title = {VPS9 domain-containing proteins are essential for autophagy and endocytosis in Pyricularia oryzae.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1516-1530}, doi = {10.1111/1462-2920.14076}, pmid = {29468804}, issn = {1462-2920}, abstract = {Pyricularia oryzae is the causal pathogen of rice blast disease. Autophagy has been shown to play important roles in P. oryzae development and plant infection. The P. oryzae endosomal system is highly dynamic and has been shown to be associated with conidiogenesis and pathogenicity as well. To date, the crosstalk between autophagy and endocytosis has not been explored in P. oryzae. Here, we identified three P. oryzae VPS9 domain-containing proteins, PoVps9, PoMuk1 and PoVrl1. We found that PoVps9 and PoMuk1 are localized to vesicles and are each co-localized with PoVps21, a recognized marker of early endosomes. Deletion of PoVPS9 resulted in severe defects in endocytosis and autophagosome degradation and impaired the localization of PoVps21 to endosomes. Additionally, deletion of the PoMUK1 gene in the ΔPovps9 mutant background exhibited more severe defects in development, autophagy and endocytosis compared with the ΔPovps9 mutant. Pull-down assay showed that PoVps9 interacts with PoVps21, PoRab11 and PoRab1, which have been verified to participate in endocytosis. Furthermore, yeast two-hybrid and co-immunoprecipitation assays confirmed that PoVps9 directly interacts with the GDP form of PoVps21. Thus, PoVps9 is a key protein involved in autophagy and in endocytosis.}, } @article {pmid29468803, year = {2018}, author = {Krukenberg, V and Riedel, D and Gruber-Vodicka, HR and Buttigieg, PL and Tegetmeyer, HE and Boetius, A and Wegener, G}, title = {Gene expression and ultrastructure of meso- and thermophilic methanotrophic consortia.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1651-1666}, pmid = {29468803}, issn = {1462-2920}, support = {294757//European Research Council/International ; }, abstract = {The sulfate-dependent, anaerobic oxidation of methane (AOM) is an important sink for methane in marine environments. It is carried out between anaerobic methanotrophic archaea (ANME) and sulfate-reducing bacteria (SRB) living in syntrophic partnership. In this study, we compared the genomes, gene expression patterns and ultrastructures of three phylogenetically different microbial consortia found in hydrocarbon-rich environments under different temperature regimes: ANME-1a/HotSeep-1 (60°C), ANME-1a/Seep-SRB2 (37°C) and ANME-2c/Seep-SRB2 (20°C). All three ANME encode a reverse methanogenesis pathway: ANME-2c encodes all enzymes, while ANME-1a lacks the gene for N5,N10-methylene tetrahydromethanopterin reductase (mer) and encodes a methylenetetrahydrofolate reductase (Met). The bacterial partners contain the genes encoding the canonical dissimilatory sulfate reduction pathway. During AOM, all three consortia types highly expressed genes encoding for the formation of flagella or type IV pili and/or c-type cytochromes, some predicted to be extracellular. ANME-2c expressed potentially extracellular cytochromes with up to 32 hemes, whereas ANME-1a and SRB expressed less complex cytochromes (≤ 8 and ≤ 12 heme respectively). The intercellular space of all consortia showed nanowire-like structures and heme-rich areas. These features are proposed to enable interspecies electron exchange, hence suggesting that direct electron transfer is a common mechanism to sulfate-dependent AOM, and that both partners synthesize molecules to enable it.}, } @article {pmid29468774, year = {2018}, author = {Ratz, T and Smiseth, PT}, title = {Flexible parents: joint effects of handicapping and brood size manipulation on female parental care in Nicrophorus vespilloides.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {646-656}, doi = {10.1111/jeb.13254}, pmid = {29468774}, issn = {1420-9101}, abstract = {Parental care is highly variable, reflecting that parents make flexible decisions in response to variation in the cost of care to themselves and the benefit to their offspring. Much of the evidence that parents respond to such variation derives from handicapping and brood size manipulations, the separate effects of which are well understood. However, little is known about their joint effects. Here, we fill this gap by conducting a joint handicapping and brood size manipulation in the burying beetle Nicrophorus vespilloides. We handicapped half of the females by attaching a lead weight to their pronotum, leaving the remaining females as controls. We also manipulated brood size by providing each female with 5, 20 or 40 larvae. In contrast to what we predicted, handicapped females spent more time provisioning food than controls. We also found that handicapped females spent more time consuming carrion. Furthermore, handicapped females spent a similar amount of time consuming carrion regardless of brood size, whereas controls spent more time consuming carrion as brood increased. Females spent more time provisioning food towards larger broods, and females were more likely to engage in carrion consumption when caring for larger broods. We conclude that females respond to both handicapping and brood size manipulations, but these responses are largely independent of each other. Overall, our results suggest that handicapping might lead to a higher investment into current reproduction and that it might be associated with compensatory responses that negate the detrimental impact of higher cost of care in handicapped parents.}, } @article {pmid29468654, year = {2018}, author = {Kohl, KP and Singh, ND}, title = {Experimental evolution across different thermal regimes yields genetic divergence in recombination fraction but no divergence in temperature associated plastic recombination.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {989-999}, doi = {10.1111/evo.13454}, pmid = {29468654}, issn = {1558-5646}, abstract = {Phenotypic plasticity is pervasive in nature. One mechanism underlying the evolution and maintenance of such plasticity is environmental heterogeneity. Indeed, theory indicates that both spatial and temporal variation in the environment should favor the evolution of phenotypic plasticity under a variety of conditions. Cyclical environmental conditions have also been shown to yield evolved increases in recombination frequency. Here, we use a panel of replicated experimental evolution populations of D. melanogaster to test whether variable environments favor enhanced plasticity in recombination rate and/or increased recombination rate in response to temperature. In contrast to expectation, we find no evidence for either enhanced plasticity in recombination or increased rates of recombination in the variable environment lines. Our data confirm a role of temperature in mediating recombination fraction in D. melanogaster, and indicate that recombination is genetically and plastically depressed under lower temperatures. Our data further suggest that the genetic architectures underlying plastic recombination and population-level variation in recombination rate are likely to be distinct.}, } @article {pmid29468305, year = {2018}, author = {Ramalho, MO and Vieira, AS and Pereira, MC and Moreau, CS and Bueno, OC}, title = {Transovarian Transmission of Blochmannia and Wolbachia Endosymbionts in the Neotropical Weaver Ant Camponotus textor (Hymenoptera, Formicidae).}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {866-873}, pmid = {29468305}, issn = {1432-0991}, support = {007343/2014-00//CAPES Foundation/ ; 157837/2015-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; }, mesh = {Animals ; Ants/growth & development/*microbiology ; Enterobacteriaceae/classification/genetics/*isolation & purification/physiology ; Female ; In Situ Hybridization, Fluorescence ; Ovary/growth & development/microbiology ; Ovum/growth & development/microbiology ; *Symbiosis ; Wolbachia/classification/genetics/*isolation & purification/physiology ; }, abstract = {Camponotus is a hyper-diverse ant genus that is associated with the obligate endosymbiont Blochmannia, and often also with Wolbachia, but morphological studies on the location of these bacteria in the queen's ovaries during oogenesis remain limited. In the present study, we used the Neotropical weaver ant Camponotus textor to characterize the ovary using histology (HE) techniques, and to document the location of Blochmannia and Wolbachia during oogenesis through fluorescence in situ hybridization (FISH). This is the first morphological report of these two bacteria in the same host with polytrophic meroistic ovaries and reveals that Blochmannia is found inside late-stage oocytes and Wolbachia is associated with the nuclei of the nurse cells. Our results provide insights into the developmental sequence of when these bacteria reach the egg, with Blochmannia establishing itself in the egg first, and Wolbachia only reaching the egg shortly before completing egg development. Studies such as this provide understanding about the mechanisms and timing of the establishment of these endosymbionts in the host.}, } @article {pmid29468304, year = {2018}, author = {Hadjilouka, A and Paramithiotis, S and Drosinos, EH}, title = {Genetic Analysis of the Listeria Pathogenicity Island 1 of Listeria monocytogenes 1/2a and 4b Isolates.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {857-865}, pmid = {29468304}, issn = {1432-0991}, support = {289719//EU/ ; }, mesh = {Bacterial Proteins/genetics ; *Genomic Islands ; Humans ; Listeria monocytogenes/classification/*genetics/isolation & purification ; Listeriosis/microbiology ; Multigene Family ; Phylogeny ; Virulence Factors/genetics ; }, abstract = {The aim of the present study was to apply descriptive, phylogenetic, recombination, and selection analyses on alignments of the Listeria Pathogenicity Island 1 (LIPI-1) of 1/2a and 4b Listeria monocytogenes isolates of different origin in order to gain insights into the evolution of this virulence gene cluster. For that purpose, a total of 19 L. monocytogenes isolates (9 meat isolates, serotype 1/2a; 5 meat isolates, serotype 4b; 5 strawberry isolates, serotype 4b) that have been previously separated at strain level were subjected to sequencing of their LIPI-1. Descriptive analysis revealed extensive nucleotide diversity mostly in the intragenic regions. The actA gene of 1/2a and 4b meat isolates and the hly gene of the 4b strawberry isolates exhibited the higher diversity; limited diversity was observed in prfA and plcA genes of the 4b isolates and mpl gene of the 1/2a isolates. Phylogenetic analysis of the complete island resulted in two major clusters that were consistent with serotype assignment of the isolates. Moreover, effective discrimination between serotypes was obtained by plcA, plcB, mpl, actA and the intergenic regions plcA-prfA and plcA-hly. In all cases but plcB and plcA-prfA 4b isolates were also differentiated according to their source of isolation as well. Selection analysis revealed that the island consisted of randomly evolving DNA with the exception of prfA gene of 1/2a isolates and actA gene of 4b meat isolates for which purifying selection or population expansion was indicated. Finally, no statistically significant evidence for recombination has been observed.}, } @article {pmid29468303, year = {2018}, author = {Peterson, CP and Sauer, C and Chatfield, CH}, title = {The Extracellular Polymeric Substances of Legionella pneumophila Biofilms Contain Amyloid Structures.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {736-744}, pmid = {29468303}, issn = {1432-0991}, support = {1337695//National Science Foundation/ ; }, mesh = {Amyloid/metabolism ; Biofilms ; Legionella pneumophila/*metabolism ; Water Microbiology ; }, abstract = {Human infection by bacteria of the genus Legionella most often result in the pneumonia known as Legionnaires Disease. Legionella is found as a resident of adherent biofilms in man-made water systems. Disinfection efforts to prevent Legionella infections require a better understanding of the structures that promote Legionella surface attachment and biofilm colonization. Various enzymatic treatments, including multiple carbohydrate-targeting mixtures, failed to disrupt Legionella biofilms, despite the presence of carbohydrates in the biofilms as shown by biochemical methods and concanavalin-A lectin staining. Moreover, Legionella biofilms contained amyloids as detected by three microscopic staining methods (congo red, thioflavin T, and the amyloid-specific antibody WO2). Amyloid structures were seen in biofilms of both L. pneumophila and L. longbeachae, the two Legionella species most associated with human infection. Inhibition of amyloid assembly by congo red and thioflavin T limited both self-aggregation and surface attachment of L. pneumophila, indicating that functional amyloid structures have a key role in initial biofilm formation by these pathogenic bacteria.}, } @article {pmid29468302, year = {2018}, author = {Kimura, Y and Tanaka, C and Oka, M}, title = {Identification of Major Enzymes Involved in the Synthesis of Diadenosine Tetraphosphate and/or Adenosine Tetraphosphate in Myxococcus xanthus.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {811-817}, pmid = {29468302}, issn = {1432-0991}, mesh = {Adenosine/metabolism ; Amino Acyl-tRNA Synthetases/genetics/metabolism ; Bacterial Proteins/genetics/*metabolism ; Biocatalysis ; Biosynthetic Pathways ; Coenzyme A Ligases/genetics/metabolism ; Dinucleoside Phosphates/*biosynthesis/genetics/metabolism ; Lysine-tRNA Ligase/genetics/metabolism ; Myxococcus xanthus/*enzymology/genetics/metabolism ; }, abstract = {Myxococcus xanthus generates diadenosine tetraphosphates (Ap4A) and diadenosine pentaphosphates (Ap5A) under various stress conditions. M. xanthus lysyl-tRNA synthetase (LysS) efficiently synthesizes Ap4A from ATP, Ap5A from ATP and adenosine tetraphosphate (Ap4), and Ap4 from ATP and triphosphate. To identify other M. xanthus enzymes that can catalyze Ap4A and Ap4 synthesis, 15 M. xanthus aminoacyl-tRNA synthetases (aaRSs), four acyl-CoA synthetases (Acys), three acetyl-CoA synthetases (Aces), phosphoglycerate kinase (Pgk), and adenylate kinase (Adk) were expressed in Escherichia coli and examined for Ap4A or Ap4 synthetase activity using ATP or ATP and triphosphate as substrates. Among the tested enzymes, LysS had the highest Ap4A synthetase activity. AlaRS, SerRS, and LeuRS1 showed high ADP synthetase activity with ATP as a substrate in the presence of pyrophosphatase, and also demonstrated the ability to produce Ap4 from ATP and triphosphate in the absence of pyrophosphatase. Ap4 formation by AlaRS, SerRS, and LeuRS1 was approximately 4- to 13-fold higher compared with that of Ap4A, suggesting that these enzymes prefer triphosphate over ATP as a substrate in the second reaction. Some of the recombinant M. xanthus Acys and Aces also synthesized Ap4 from ATP and triphosphate. However, Pgk was capable of catalyzing the production of Ap4 from ATP and 3-phosphoglycerate in the presence of Mg2+ and did not require triphosphate, suggesting that this enzyme is mainly responsible for Ap4 synthesis in M. xanthus.}, } @article {pmid29468301, year = {2018}, author = {Wu, J and Stewart, JR and Sobsey, MD and Cormency, C and Fisher, MB and Bartram, JK}, title = {Rapid Detection of Escherichia coli in Water Using Sample Concentration and Optimized Enzymatic Hydrolysis of Chromogenic Substrates.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {827-834}, pmid = {29468301}, issn = {1432-0991}, support = {43171142//Fondation UNICE/ ; 2014-1751-02//North Carolina Sea Grant/ ; }, mesh = {Biological Assay/instrumentation/*methods ; Chromogenic Compounds/*chemistry/metabolism ; Escherichia coli/*enzymology/isolation & purification/metabolism ; Escherichia coli Proteins/*chemistry/metabolism ; Feces/chemistry/microbiology ; Fresh Water/*microbiology ; Glucuronates/*chemistry/metabolism ; Glucuronidase/*chemistry/metabolism ; Hydrolysis ; Indoles/*chemistry/metabolism ; Oxazines/chemistry/metabolism ; Water Pollutants, Chemical/*chemistry/metabolism ; Water Pollution, Chemical ; }, abstract = {Methods for rapid detection of fecal indicator bacteria in water are important to ensure that water is safe for drinking, bathing, recreation, fishing and shellfish harvesting. In this study, we tested experimental conditions for bacterial hydrolysis of two promising enzymatic substrates, 5-Bromo-4-chloro-3-indolyl β-D-glucuronide (X-Gluc) and Resorufin β-D-glucuronide (REG), and optimized parameters such as temperature and pH to determine conditions for rapid reactions. We then innovated a membrane filter-based approach to facilitate more rapid enzyme-based detection of Escherichia coli in water based on the combination of an initial concentration step and optimized test conditions. For this approach, a water sample (10‒100 mL) is filtered through a 0.45-µm pore size filter with a diameter of 4 or 13 mm. After filtration, a newly designed rapid detection broth is added containing the enzymatic inducer Methyl-beta-D-Glucuronide sodium (MetGlu) and the substrate REG or X-Gluc. After a few (1‒7) hours of incubation at 35 °C, the filter shows pink color (for REG-containing broth) or green color (for X-Gluc containing broth) if E. coli is present. The study provides insights and approaches towards developing a simple, fast, and low-cost method to detect fecal indicator bacteria in water.}, } @article {pmid29468050, year = {2018}, author = {Coogan, SCP and Raubenheimer, D and Stenhouse, GB and Coops, NC and Nielsen, SE}, title = {Functional macronutritional generalism in a large omnivore, the brown bear.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2365-2376}, pmid = {29468050}, issn = {2045-7758}, abstract = {We combine a recently developed framework for describing dietary generalism with compositional data analysis to examine patterns of omnivory in a large widely distributed mammal. Using the brown bear (Ursus arctos) as a model species, we collected and analyzed data from the literature to estimate the proportions of macronutrients (protein, carbohydrate, and lipid) in the diets of bear populations. Across their range, bears consumed a diversity of foods that resulted in annual population diets that varied in macronutrient proportions, suggesting a wide fundamental macronutrient niche. The variance matrix of pairwise macronutrient log-ratios indicated that the most variable macronutrient among diets was carbohydrate, while protein and lipid were more proportional or codependent (i.e., relatively more constant log-ratios). Populations that consumed anthropogenic foods, such agricultural crops and supplementary feed (e.g., corn), had a higher geometric mean proportion of carbohydrate, and lower proportion of protein, in annual diets. Seasonally, mean diets were lower in protein and higher in carbohydrate, during autumn compared to spring. Populations with anthropogenic subsidies, however, had higher mean proportions of carbohydrate and lower protein, across seasons compared to populations with natural diets. Proportions of macronutrients similar to those selected in experiments by captive brown bears, and which optimized primarily fat mass gain, were observed among hyperphagic prehibernation autumn diets. However, the majority of these were from populations consuming anthropogenic foods, while diets of natural populations were more variable and typically higher in protein. Some anthropogenic diets were close to the proportions selected by captive bears during summer. Our results suggest that omnivory in brown bears is a functional adaptation enabling them to occupy a diverse range of habitats and tolerate variation in the nutritional composition and availability of food resources. Furthermore, we show that populations consuming human-sourced foods have different dietary macronutrient proportions relative to populations with natural diets.}, } @article {pmid29468049, year = {2018}, author = {Bluhm, BA and Hop, H and Vihtakari, M and Gradinger, R and Iken, K and Melnikov, IA and Søreide, JE}, title = {Sea ice meiofauna distribution on local to pan-Arctic scales.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2350-2364}, pmid = {29468049}, issn = {2045-7758}, abstract = {Arctic sea ice provides microhabitats for biota that inhabit the liquid-filled network of brine channels and the ice-water interface. We used meta-analysis of 23 published and unpublished datasets comprising 721 ice cores to synthesize the variability in composition and abundance of sea ice meiofauna at spatial scales ranging from within a single ice core to pan-Arctic and seasonal scales. Two-thirds of meiofauna individuals occurred in the bottom 10 cm of the ice. Locally, replicate cores taken within meters of each other were broadly similar in meiofauna composition and abundance, while those a few km apart varied more; 75% of variation was explained by station. At the regional scale (Bering Sea first-year ice), meiofauna abundance varied over two orders of magnitude. At the pan-Arctic scale, the same phyla were found across the region, with taxa that have resting stages or tolerance to extreme conditions (e.g., nematodes and rotifers) dominating abundances. Meroplankton, however, was restricted to nearshore locations and landfast sea ice. Light availability, ice thickness, and distance from land were significant predictor variables for community composition on different scales. On a seasonal scale, abundances varied broadly for all taxa and in relation to the annual ice algal bloom cycle in both landfast and pack ice. Documentation of ice biota composition, abundance, and natural variability is critical for evaluating responses to decline in Arctic sea ice. Consistent methodology and protocols must be established for comparability of meiofauna monitoring across the Arctic. We recommend to (1) increase taxonomic resolution of sea ice meiofauna, (2) focus sampling on times of peak abundance when seasonal sampling is impossible, (3) include the bottom 30 cm of ice cores rather than only bottom 10 cm, (4) preserve specimens for molecular analysis to improve taxonomic resolution, and (5) formulate a trait-based framework that relates to ecosystem functioning.}, } @article {pmid29468048, year = {2018}, author = {Beirão, J and Lewis, JA and Wringe, BF and Purchase, CF}, title = {A novel sperm adaptation to evolutionary constraints on reproduction: Pre-ejaculatory sperm activation in the beach spawning capelin (Osmeridae).}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2343-2349}, pmid = {29468048}, issn = {2045-7758}, abstract = {Reproduction of external fertilizing vertebrates is typically constrained to either fresh or salt water, not both. For all studied amphibians and fishes, this constraint includes immotile sperm that are activated after ejaculation only by the specific chemistry of the fertilizing medium in which the species evolved (fresh, brackish, or salt water). No amphibians can reproduce in the sea. Although diadromous fishes may migrate between salt and fresh water, they are shackled to their natal environment for spawning in part because of sperm activation. Here, we report for the first time among all documented external fertilizing vertebrates, that in the absence of any external media, sperm are motile at ejaculation in a marine spawning fish (Osmeridae, capelin, Mallotus villosus). To illuminate why, we evaluated sperm behavior at different salinities in M. villosus as well as the related freshwater spawning anadromous rainbow smelt (Osmerus mordax). Surprisingly, sperm performance was superior in fresh water for both species. M. villosus spend their entire life at sea but our results show that their sperm are deactivated by sea water, suggesting a freshwater ancestry. By circumventing constraining water chemistry, we interpret the unique pre-ejaculatory sperm activation in this species as a novel adaptation that enables fertilization in the marine environment. These findings also contribute to understanding the persistence of anadromy, despite great energetic costs to adult fishes.}, } @article {pmid29468047, year = {2018}, author = {Stobie, CS and Oosthuizen, CJ and Cunningham, MJ and Bloomer, P}, title = {Exploring the phylogeography of a hexaploid freshwater fish by RAD sequencing.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2326-2342}, pmid = {29468047}, issn = {2045-7758}, abstract = {The KwaZulu-Natal yellowfish (Labeobarbus natalensis) is an abundant cyprinid, endemic to KwaZulu-Natal Province, South Africa. In this study, we developed a single-nucleotide polymorphism (SNP) dataset from double-digest restriction site-associated DNA (ddRAD) sequencing of samples across the distribution. We addressed several hidden challenges, primarily focusing on proper filtering of RAD data and selecting optimal parameters for data processing in polyploid lineages. We used the resulting high-quality SNP dataset to investigate the population genetic structure of L. natalensis. A small number of mitochondrial markers present in these data had disproportionate influence on the recovered genetic structure. The presence of singleton SNPs also confounded genetic structure. We found a well-supported division into northern and southern lineages, with further subdivision into five populations, one of which reflects north-south admixture. Approximate Bayesian Computation scenario testing supported a scenario where an ancestral population diverged into northern and southern lineages, which then diverged to yield the current five populations. All river systems showed similar levels of genetic diversity, which appears unrelated to drainage system size. Nucleotide diversity was highest in the smallest river system, the Mbokodweni, which, together with adjacent small coastal systems, should be considered as a key catchment for conservation.}, } @article {pmid29468046, year = {2018}, author = {Wu, Y and Du, Q and Qin, H and Shi, J and Wu, Z and Shao, W}, title = {Rapid identification of the Asian gypsy moth and its related species based on mitochondrial DNA.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2320-2325}, pmid = {29468046}, issn = {2045-7758}, abstract = {The gypsy moth-Lymantria dispar (Linnaeus)-is a worldwide forest defoliator and is of two types: the European gypsy moth and the Asian gypsy moth. Because of multiple invasions of the Asian gypsy moth, the North American Plant Protection Organization officially approved Regional Standards for Phytosanitary Measures No. 33. Accordingly, special quarantine measures have been implemented for 30 special focused ports in the epidemic areas of the Asian gypsy moth, including China, which has imposed great inconvenience on export trade. The Asian gypsy moth and its related species (i.e., Lymantria monocha and Lymantria xylina) intercepted at ports are usually at different life stages, making their identification difficult. Furthermore, Port quarantine requires speedy clearance. As such, it is difficult to identify the Asian gypsy moth and its related species only by their morphological characteristics in a speedy measure. Therefore, this study aimed to use molecular biology technology to rapidly identify the Asian gypsy moth and its related species based on the consistency of mitochondrial DNA in different life stages. We designed 10 pairs of specific primers from different fragments of the Asian gypsy moth and its related species, and their detection sensitivity met the need for rapid identification. In addition, we determined the optimal polymerase chain reaction amplification temperature of the 10 pairs of specific primers, including three pairs of specific primers for the Asian gypsy moth (L. dispar asiatic), four pairs of specific primers for the nun moth (L. monocha), and three pairs of specific primers for the casuarina moth (L. xylina). In conclusion, using our designed primers, direct rapid identification of the Asian gypsy moth and its related species is possible, and this advancement can help improve export trade in China.}, } @article {pmid29468045, year = {2018}, author = {Nishimura, K}, title = {An interaction-driven cannibalistic reaction norm.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2305-2319}, pmid = {29468045}, issn = {2045-7758}, abstract = {Cannibalism is induced in larval-stage populations of the Hokkaido salamander, Hynobius retardatus, under the control of a cannibalism reaction norm. Here, I examined phenotypic expression under the cannibalism reaction norm, and how the induction of a cannibalistic morph under the norm leads to populational morphological diversification. I conducted a set of experiments in which density was manipulated to be either low or high. In the high-density treatment, the populations become dimorphic with some individuals developing into the cannibal morph type. I performed an exploratory analysis based on geometric morphometrics and showed that shape characteristics differed between not only cannibal and noncannibal morph types in the high-density treatment but also between those morph types and the solitary morph type in the low-density treatment. Size and shape of cannibal and noncannibal individuals were found to be located at either end of a continuum of expression following a unique size-shape integration rule that was different from the rule governing the size and shape variations of the solitary morph type. This result implies that the high-density-driven inducible morphology of an individual is governed by a common integration rule during the development of dimorphism under the control of the cannibalism reaction norm. Phenotypic expression under the cannibalism reaction norm is driven not only by population density but also by social interactions among the members of a population: variation in the populational expression of dimorphism is associated with contingent social interaction events among population members. The induced cannibalistic morph thus reflects not only by contest-type exploitative competition but also interference competition.}, } @article {pmid29468044, year = {2018}, author = {Steyer, K and Tiesmeyer, A and Muñoz-Fuentes, V and Nowak, C}, title = {Low rates of hybridization between European wildcats and domestic cats in a human-dominated landscape.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2290-2304}, pmid = {29468044}, issn = {2045-7758}, abstract = {Hybridization between wild species and their domestic congeners is considered a major threat for wildlife conservation. Genetic integrity of the European wildcat, for instance, is a concern as they are outnumbered by domestic cats by several orders of magnitude throughout its range. We genotyped 1,071 individual wildcat samples obtained from hair traps and roadkills collected across the highly fragmented forests of western Central Europe, in Germany and Luxembourg, to assess domestic cat introgression in wildcats in human-dominated landscapes. Analyses using a panel of 75 autosomal SNPs suggested a low hybridization rate, with 3.5% of wildcat individuals being categorized as F1, F2, or backcrosses to either parental taxon. We report that results based on a set of SNPs were more consistent than on a set of 14 microsatellite markers, showed higher accuracy to detect hybrids and their class in simulation analyses, and were less affected by underlying population structure. Our results strongly suggest that very high hybridization rates previously reported for Central Europe may be partly due to inadequate choice of markers and/or sampling design. Our study documents that an adequately selected SNP panel for hybrid detection may be used as an alternative to commonly applied microsatellite markers, including studies relying on noninvasively collected samples. In addition, our finding of overall low hybridization rates in Central European wildcats provides an example of successful wildlife coexistence in human-dominated, fragmented landscapes.}, } @article {pmid29468043, year = {2018}, author = {Bukowski, AR and Schittko, C and Petermann, JS}, title = {The strength of negative plant-soil feedback increases from the intraspecific to the interspecific and the functional group level.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2280-2289}, pmid = {29468043}, issn = {2045-7758}, abstract = {One of the processes that may play a key role in plant species coexistence and ecosystem functioning is plant-soil feedback, the effect of plants on associated soil communities and the resulting feedback on plant performance. Plant-soil feedback at the interspecific level (comparing growth on own soil with growth on soil from different species) has been studied extensively, while plant-soil feedback at the intraspecific level (comparing growth on own soil with growth on soil from different accessions within a species) has only recently gained attention. Very few studies have investigated the direction and strength of feedback among different taxonomic levels, and initial results have been inconclusive, discussing phylogeny, and morphology as possible determinants. To test our hypotheses that the strength of negative feedback on plant performance increases with increasing taxonomic level and that this relationship is explained by morphological similarities, we conducted a greenhouse experiment using species assigned to three taxonomic levels (intraspecific, interspecific, and functional group level). We measured certain fitness-related aboveground traits and used them along literature-derived traits to determine the influence of morphological similarities on the strength and direction of the feedback. We found that the average strength of negative feedback increased from the intraspecific over the interspecific to the functional group level. However, individual accessions and species differed in the direction and strength of the feedback. None of our results could be explained by morphological dissimilarities or individual traits. Synthesis. Our results indicate that negative plant-soil feedback is stronger if the involved plants belong to more distantly related species. We conclude that the taxonomic level is an important factor in the maintenance of plant coexistence with plant-soil feedback as a potential stabilizing mechanism and should be addressed explicitly in coexistence research, while the traits considered here seem to play a minor role.}, } @article {pmid29468042, year = {2018}, author = {Guzy, JC and Eskew, EA and Halstead, BJ and Price, SJ}, title = {Influence of damming on anuran species richness in riparian areas: A test of the serial discontinuity concept.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2268-2279}, pmid = {29468042}, issn = {2045-7758}, abstract = {Almost all large rivers worldwide are fragmented by dams, and their impacts have been modeled using the serial discontinuity concept (SDC), a series of predictions regarding responses of key biotic and abiotic variables. We evaluated the effects of damming on anuran communities along a 245-km river corridor by conducting repeated, time-constrained anuran calling surveys at 42 locations along the Broad and Pacolet Rivers in South Carolina, USA. Using a hierarchical Bayesian analysis, we test the biodiversity prediction of the SDC (modified for floodplain rivers) by evaluating anuran occupancy and species diversity relative to dams and degree of urbanized land use. The mean response of the anuran community indicated that occupancy and species richness were maximized when sites were farther downstream from dams. Sites at the farthest distances downstream of dams (47.5 km) had an estimated ~3 more species than those just below dams. Similarly, species-specific occupancy estimates showed a trend of higher occupancy downstream from dams. Therefore, using empirical estimation within the context of a 245-km river riparian landscape, our study supports SDC predictions for a meandering river. We demonstrate that with increasing distance downstream from dams, riparian anuran communities have higher species richness. Reduced species richness immediately downstream of dams is likely driven by alterations in flow regime that reduce or eliminate flows which sustain riparian wetlands that serve as anuran breeding habitat. Therefore, to maintain anuran biodiversity, we suggest that flow regulation should be managed to ensure water releases inundate riparian wetlands during amphibian breeding seasons and aseasonal releases, which can displace adults, larvae, and eggs, are avoided. These outcomes could be achieved by emulating pre-dam seasonal discharge data, mirroring discharge of an undammed tributary within the focal watershed, or by basing real-time flow releases on current environmental conditions.}, } @article {pmid29468041, year = {2018}, author = {Morse, P and Kjeldsen, SR and Meekan, MG and Mccormick, MI and Finn, JK and Huffard, CL and Zenger, KR}, title = {Genome-wide comparisons reveal a clinal species pattern within a holobenthic octopod-the Australian Southern blue-ringed octopus, Hapalochlaena maculosa (Cephalopoda: Octopodidae).}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2253-2267}, pmid = {29468041}, issn = {2045-7758}, abstract = {The southern blue-ringed octopus, Hapalochlaena maculosa (Hoyle, 1883) lacks a planktonic dispersal phase, yet ranges across Australia's southern coastline. This species' brief and holobenthic life history suggests gene flow might be limited, leaving distant populations prone to strong genetic divergence. This study used 17,523 genome-wide SNP loci to investigate genetic structuring and local adaptation patterns of H. maculosa among eight sampling sites along its reported range. Within sites, interrelatedness was very high, consistent with the limited dispersal of this taxon. However, inbreeding coefficients were proportionally lower among sites where substructuring was not detected, suggesting H. maculosa might possess a mechanism for inbreeding avoidance. Genetic divergence was extremely high among all sites, with the greatest divergence observed between both ends of the distribution, Fremantle, WA, and Stanley, TAS. Genetic distances closely followed an isolation by geographic distance pattern. Outlier analyses revealed distinct selection signatures at all sites, with the strongest divergence reported between Fremantle and the other Western Australian sites. Phylogenetic reconstructions using the described sister taxon H. fasciata (Hoyle, 1886) further supported that the genetic divergence between distal H. maculosa sites in this study was equivalent to that of between established heterospecifics within this genus. However, it is advocated that taxonomic delineations within this species should be made with caution. These data indicate that H. maculosa forms a clinal species pattern across its geographic range, with gene flow present through allele sharing between adjacent populations. Morphological investigations are recommended for a robust resolution of the taxonomic identity and ecotype boundaries of this species.}, } @article {pmid29468040, year = {2018}, author = {Pogoreutz, C and Rädecker, N and Cárdenas, A and Gärdes, A and Wild, C and Voolstra, CR}, title = {Dominance of Endozoicomonas bacteria throughout coral bleaching and mortality suggests structural inflexibility of the Pocillopora verrucosa microbiome.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2240-2252}, pmid = {29468040}, issn = {2045-7758}, abstract = {The importance of Symbiodinium algal endosymbionts and a diverse suite of bacteria for coral holobiont health and functioning are widely acknowledged. Yet, we know surprisingly little about microbial community dynamics and the stability of host-microbe associations under adverse environmental conditions. To gain insight into the stability of coral host-microbe associations and holobiont structure, we assessed changes in the community structure of Symbiodinium and bacteria associated with the coral Pocillopora verrucosa under excess organic nutrient conditions. Pocillopora-associated microbial communities were monitored over 14 days in two independent experiments. We assessed the effect of excess dissolved organic nitrogen (DON) and excess dissolved organic carbon (DOC). Exposure to excess nutrients rapidly affected coral health, resulting in two distinct stress phenotypes: coral bleaching under excess DOC and severe tissue sloughing (>90% tissue loss resulting in host mortality) under excess DON. These phenotypes were accompanied by structural changes in the Symbiodinium community. In contrast, the associated bacterial community remained remarkably stable and was dominated by two Endozoicomonas phylotypes, comprising on average 90% of 16S rRNA gene sequences. This dominance of Endozoicomonas even under conditions of coral bleaching and mortality suggests the bacterial community of P. verrucosa may be rather inflexible and thereby unable to respond or acclimatize to rapid changes in the environment, contrary to what was previously observed in other corals. In this light, our results suggest that coral holobionts might occupy structural landscapes ranging from a highly flexible to a rather inflexible composition with consequences for their ability to respond to environmental change.}, } @article {pmid29468039, year = {2018}, author = {Lobo, A and Hansen, JK and Hansen, LN and Dahl Kjær, E}, title = {Differences among six woody perennials native to Northern Europe in their level of genetic differentiation and adaptive potential at fine local scale.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2231-2239}, pmid = {29468039}, issn = {2045-7758}, abstract = {The ability of perennial species to adapt their phenology to present and future temperature conditions is important for their ability to retain high fitness compared to other competing plant species, pests, and pathogens. Many transplanting studies with forest tree species have previously reported substantial genetic differentiation among populations within their native range. However, the question of "how local is local" is still highly debated in conservation biology because studies on genetic patterns of variation within and among populations at the local scale are limited and scattered. In this study, we compare the level of genetic differentiation among populations of six different perennial plant species based on their variation in spring flushing. We assess the level of additive genetic variation present within the local population. For all six species, we find significant differentiation among populations from sites with mean annual temperature ranging between 7.4°C and 8.4°C. The observed variation can only be partly explained by the climate at the site of origin. Most clear relationship between early flushing and higher average spring temperature is observed for the three wind-pollinated species in the study, while the relations are much less clear for the three insect-pollinated species. This supports that pollination system can influence the balance between genetic drift and natural selection and thereby influence the level of local adaptation in long-lived species. On the positive side, we find that the native populations of woody plant species have maintained high levels of additive genetic variation in spring phenology, although this also differs substantially among the six studied species.}, } @article {pmid29468038, year = {2018}, author = {Chen, K and Burgess, KS and Yang, XY and Luo, YH and Gao, LM and Li, DZ}, title = {Functional trade-offs and the phylogenetic dispersion of seed traits in a biodiversity hotspot of the Mountains of Southwest China.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2218-2230}, pmid = {29468038}, issn = {2045-7758}, abstract = {The diversity of traits associated with plant regeneration is often shaped by functional trade-offs where plants typically do not excel at every function because resources allocated to one function cannot be allocated to another. By analyzing correlations among seed traits, empirical studies have shown that there is a trade-off between seedling development and the occupation of new habitats, although only a small range of taxa have been tested; whether such trade-off exists in a biodiverse and complex landscape remains unclear. Here, we amassed seed trait data of 1,119 species from a biodiversity hotspot of the Mountains of Southwest China and analyzed the relationship between seed mass and the number of seeds and between seed mass and time to germination. Our results showed that seed mass was negatively correlated with seed number but positively correlated with time to germination. The same trend was found regardless of variation in life-form and phylogenetic conservatism. Furthermore, the relation between seed mass and other seed traits was randomly dispersed across the phylogeny at both the order and family levels. Collectively, results suggest that there is a functional trade-off between seedling development and new habitat occupation for seed plants in this region. Larger seeds tend to produce fewer seedlings but with greater fitness compared to those produced by smaller seeds, whereas smaller seeds tend to have a larger number of seeds that germinate faster compared to large-seeded species. Apart from genetic constraints, species that produce large seeds will succeed in sites where resource availability is low, whereas species with high colonization ability (those that produce a high number of seeds per fruit) will succeed in new niches. This study provides a mechanistic explanation for the relatively high levels of plant diversity currently found in a heterogeneous region of the Mountains of Southwest China.}, } @article {pmid29468037, year = {2018}, author = {Bourgeois, S and Senn, H and Kaden, J and Taggart, JB and Ogden, R and Jeffery, KJ and Bunnefeld, N and Abernethy, K and McEwing, R}, title = {Single-nucleotide polymorphism discovery and panel characterization in the African forest elephant.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2207-2217}, pmid = {29468037}, issn = {2045-7758}, abstract = {The continuing decline in forest elephant (Loxodonta cyclotis) numbers due to poaching and habitat reduction is driving the search for new tools to inform management and conservation. For dense rainforest species, basic ecological data on populations and threats can be challenging and expensive to collect, impeding conservation action in the field. As such, genetic monitoring is being increasingly implemented to complement or replace more burdensome field techniques. Single-nucleotide polymorphisms (SNPs) are particularly cost-effective and informative markers that can be used for a range of practical applications, including population census, assessment of human impact on social and genetic structure, and investigation of the illegal wildlife trade. SNP resources for elephants are scarce, but next-generation sequencing provides the opportunity for rapid, inexpensive generation of SNP markers in nonmodel species. Here, we sourced forest elephant DNA from 23 samples collected from 10 locations within Gabon, Central Africa, and applied double-digest restriction-site-associated DNA (ddRAD) sequencing to discover 31,851 tags containing SNPs that were reduced to a set of 1,365 high-quality candidate SNP markers. A subset of 115 candidate SNPs was then selected for assay design and validation using 56 additional samples. Genotyping resulted in a high conversion rate (93%) and a low per allele error rate (0.07%). This study provides the first panel of 107 validated SNP markers for forest elephants. This resource presents great potential for new genetic tools to produce reliable data and underpin a step-change in conservation policies for this elusive species.}, } @article {pmid29468036, year = {2018}, author = {El-Gabbas, A and Dormann, CF}, title = {Wrong, but useful: regional species distribution models may not be improved by range-wide data under biased sampling.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2196-2206}, pmid = {29468036}, issn = {2045-7758}, abstract = {Species distribution modeling (SDM) is an essential method in ecology and conservation. SDMs are often calibrated within one country's borders, typically along a limited environmental gradient with biased and incomplete data, making the quality of these models questionable. In this study, we evaluated how adequate are national presence-only data for calibrating regional SDMs. We trained SDMs for Egyptian bat species at two different scales: only within Egypt and at a species-specific global extent. We used two modeling algorithms: Maxent and elastic net, both under the point-process modeling framework. For each modeling algorithm, we measured the congruence of the predictions of global and regional models for Egypt, assuming that the lower the congruence, the lower the appropriateness of the Egyptian dataset to describe the species' niche. We inspected the effect of incorporating predictions from global models as additional predictor ("prior") to regional models, and quantified the improvement in terms of AUC and the congruence between regional models run with and without priors. Moreover, we analyzed predictive performance improvements after correction for sampling bias at both scales. On average, predictions from global and regional models in Egypt only weakly concur. Collectively, the use of priors did not lead to much improvement: similar AUC and high congruence between regional models calibrated with and without priors. Correction for sampling bias led to higher model performance, whatever prior used, making the use of priors less pronounced. Under biased and incomplete sampling, the use of global bats data did not improve regional model performance. Without enough bias-free regional data, we cannot objectively identify the actual improvement of regional models after incorporating information from the global niche. However, we still believe in great potential for global model predictions to guide future surveys and improve regional sampling in data-poor regions.}, } @article {pmid29468035, year = {2018}, author = {Healey, AJE and McKeown, NJ and Taylor, AL and Provan, J and Sauer, W and Gouws, G and Shaw, PW}, title = {Cryptic species and parallel genetic structuring in Lethrinid fish: Implications for conservation and management in the southwest Indian Ocean.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2182-2195}, pmid = {29468035}, issn = {2045-7758}, abstract = {Analysis of genetic variation can provide insights into ecological and evolutionary diversification which, for commercially harvested species, can also be relevant to the implementation of spatial management strategies and sustainability. In comparison with other marine biodiversity hot spots, there has been less genetic research on the fauna of the southwest Indian Ocean (SWIO). This is epitomized by the lack of information for lethrinid fish, which support socioeconomically important fisheries in the region. This study combines comparative phylogeographic and population genetic analyses with ecological niche modeling to investigate historical and contemporary population dynamics of two species of emperor fish (Lethrinus mahsena and Lethrinus harak) across the SWIO. Both species shared similarly shallow phylogeographic patterns and modeled historical (LGM) habitat occupancies. For both species, allele frequency and kinship analyses of microsatellite variation revealed highly significant structure with no clear geographical pattern and nonrandom genetic relatedness among individuals within samples. The genetic patterns for both species indicate recurrent processes within the region that prevent genetic mixing, at least on timescales of interest to fishery managers, and the potential roles of recruitment variability and population isolation are discussed in light of biological and environmental information. This consistency in both historical and recurrent population processes indicates that the use of model species may be valuable in management initiatives with finite resources to predict population structure, at least in cases wherein biogeographic and ecological differences between taxa are minimized. Paradoxically, mtDNA sequencing and microsatellite analysis of samples from the Seychelles revealed a potential cryptic species occurring in sympatry with, and seemingly morphologically identical to, L. mahsena. BLAST results point to the likely misidentification of species and incongruence between voucher specimens, DNA barcodes, and taxonomy within the group, which highlights the utility and necessity of genetic approaches to characterize baseline biodiversity in the region before such model-based methods are employed.}, } @article {pmid29468034, year = {2018}, author = {Gallien, L and Zurell, D and Zimmermann, NE}, title = {Frequency and intensity of facilitation reveal opposing patterns along a stress gradient.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2171-2181}, pmid = {29468034}, issn = {2045-7758}, abstract = {Disentangling the different processes structuring ecological communities is a long-standing challenge. In species-rich ecosystems, most emphasis has so far been given to environmental filtering and competition processes, while facilitative interactions between species remain insufficiently studied. Here, we propose an analysis framework that not only allows for identifying pairs of facilitating and facilitated species, but also estimates the strength of facilitation and its variation along environmental gradients. Our framework combines the analysis of both co-occurrence and co-abundance patterns using a moving window approach along environmental gradients to control for potentially confounding effects of environmental filtering in the co-abundance analysis. We first validate our new approach against community assembly simulations, and exemplify its potential on a large 1,134 plant community plots dataset. Our results generally show that facilitation intensity was strongest under cold stress, whereas the proportion of facilitating and facilitated species was higher under drought stress. Moreover, the functional distance between individual facilitated species and their facilitating species significantly changed along the temperature-moisture gradient, and seemed to influence facilitation intensity, although no general positive or general negative trend was discernible among species. The main advantages of our robust framework are as follows: It enables detecting facilitating and facilitated species in species-rich systems, and it allows identifying the directionality and intensity of facilitation in species pairs as well as its variation across long environmental gradients. It thus opens numerous opportunities for incorporating functional (and phylogenetic) information in the analysis of facilitation patterns. Our case study indicated high complexity in facilitative interactions across the stress gradient and revealed new evidence that facilitation, similarly to competition, can operate between functionally similar and dissimilar species. Extending the analyses to other taxa and ecosystems will foster our understanding how complex interspecific interactions promote biodiversity.}, } @article {pmid29468033, year = {2018}, author = {Lesniak, I and Heckmann, I and Franz, M and Greenwood, AD and Heitlinger, E and Hofer, H and Krone, O}, title = {Recolonizing gray wolves increase parasite infection risk in their prey.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2160-2170}, pmid = {29468033}, issn = {2045-7758}, abstract = {The recent recolonization of Central Europe by the European gray wolf (Canis lupus) provides an opportunity to study the dynamics of parasite transmission for cases when a definitive host returns after a phase of local extinction. We investigated whether a newly established wolf population increased the prevalence of those parasites in ungulate intermediate hosts representing wolf prey, whether some parasite species are particularly well adapted to wolves, and the potential basis for such adaptations. We recorded Sarcocystis species richness in wolves and Sarcocystis prevalence in ungulates harvested in study sites with and without permanent wolf presence in Germany using microscopy and DNA metabarcoding. Sarcocystis prevalence in red deer (Cervus elaphus) was significantly higher in wolf areas (79.7%) than in control areas (26.3%) but not in roe deer (Capreolus capreolus) (97.2% vs. 90.4%) or wild boar (Sus scrofa) (82.8% vs. 64.9%). Of 11 Sarcocystis species, Sarcocystis taeniata and Sarcocystis grueneri occurred more often in wolves than expected from the Sarcocystis infection patterns of ungulate prey. Both Sarcocystis species showed a higher increase in prevalence in ungulates in wolf areas than other Sarcocystis species, suggesting that they are particularly well adapted to wolves, and are examples of "wolf specialists". Sarcocystis species richness in wolves was significantly higher in pups than in adults. "Wolf specialists" persisted during wolf maturation. The results of this study demonstrate that (1) predator-prey interactions influence parasite prevalence, if both predator and prey are part of the parasite life cycle, (2) mesopredators do not necessarily replace the apex predator in parasite transmission dynamics for particular parasites of which the apex predator is the definitive host, even if meso- and apex predators were from the same taxonomic family (here: Canidae, e.g., red foxes Vulpes vulpes), and (3) age-dependent immune maturation contributes to the control of protozoan infection in wolves.}, } @article {pmid29468032, year = {2018}, author = {Fowler-Finn, KD and Kilmer, JT and Cruz, DC and Rodríguez, RL}, title = {Female mate choice of male signals is unlikely to promote ecological adaptation in Enchenopa treehoppers (Hemiptera: Membracidae).}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2146-2159}, pmid = {29468032}, issn = {2045-7758}, abstract = {A key question in speciation research is how ecological and sexual divergence arise and interact. We tested the hypothesis that mate choice causes local adaptation and ecological divergence using the rationale that the performance~signal trait relationship should parallel the attractiveness~signal trait relationship. We used female fecundity as a measure of ecological performance. We used a species in the Enchenopa binotata treehopper complex, wherein speciation involves adaptation to novel environments and divergence in sexual communication. We used a full-sibling, split-family rearing design to estimate genetic correlations (rG) between fecundity and signal traits, and compared those relationships against population-level mate preferences for the signal traits. Animal model estimates for rG between female fecundity and male signal traits overlapped zero-rejecting the hypothesis-but could reflect sample size limitations. The magnitude of rG correlated with the strength of the mate preferences for the corresponding signal traits, especially for signal frequency, which has the strongest mate preference and the most divergence in the complex. However, signal frequencies favored by the population-level mate preference are not associated with high fecundity. Therefore, mate preferences do not appear to have been selected to favor high-performance genotypes. Our findings suggest that ecological and sexual divergence may arise separately, but reinforce each other, during speciation.}, } @article {pmid29468031, year = {2018}, author = {Lin, Z and Qin, Y and Page, P and Wang, S and Li, L and Wen, Z and Hu, F and Neumann, P and Zheng, H and Dietemann, V}, title = {Reproduction of parasitic mites Varroa destructor in original and new honeybee hosts.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2135-2145}, pmid = {29468031}, issn = {2045-7758}, abstract = {The ectoparasitic mite, Varroa destructor, shifted host from the eastern honeybee, Apis cerana, to the western honeybee, Apis mellifera. Whereas the original host survives infestations by this parasite, they are lethal to colonies of its new host. Here, we investigated a population of A. cerana naturally infested by the V. destructor Korea haplotype that gave rise to the globally invasive mite lineage. Our aim was to better characterize traits that allow for the survival of the original host to infestations by this particular mite haplotype. A known major trait of resistance is the lack of mite reproduction on worker brood in A. cerana. We show that this trait is neither due to a lack of host attractiveness nor of reproduction initiation by the parasite. However, successful mite reproduction was prevented by abnormal host development. Adult A. cerana workers recognized this state and removed hosts and parasites, which greatly affected the fitness of the parasite. These results confirm and complete previous observations of brood susceptibility to infestation in other honeybee host populations, provide new insights into the coevolution between hosts and parasites in this system, and may contribute to mitigating the large-scale colony losses of A. mellifera due to V. destructor.}, } @article {pmid29468030, year = {2018}, author = {Smith, SL and Senn, HV and Pérez-Espona, S and Wyman, MT and Heap, E and Pemberton, JM}, title = {Introgression of exotic Cervus (nippon and canadensis) into red deer (Cervus elaphus) populations in Scotland and the English Lake District.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2122-2134}, pmid = {29468030}, issn = {2045-7758}, abstract = {Since the mid-19th century, multiple introductions of Japanese sika deer (Cervus nippon nippon) and North American wapiti (C. canadensis) have taken place in the British Isles. While wapiti have generally been unsuccessful, sika have been very successful, especially in Scotland where they now overlap at least 40% of the range of native red deer (C. elaphus). Hybridization between these two species and red deer has been demonstrated in captivity and in the wild. Using a panel of 22 microsatellite loci that are highly diagnostic between red deer and sika, and moderately diagnostic between red deer and wapiti, we investigated the extent of introgression between these species in 2,943 deer sampled from around Scotland and from the English Lake District using the Bayesian clustering software STRUCTURE. We also used a diagnostic mitochondrial marker for red deer and sika. Our survey extends previous studies indicating little introgression of wapiti nuclear alleles into red deer, in particular in Northern Scotland, Kintyre, and the Lake District. We found a new area of extensive sika introgression in South Kintyre. In the North Highlands, we show for the first time geographically scattered evidence of past hybridization followed by extensive backcrossing, including one red-like individual with sika introgression, two sika-like individuals with red deer introgression, and six individuals that were apparently pure sika at the nuclear markers assessed but which carried red deer mitochondria. However, there has not been a collapse of assortative mating in this region. Similarly, in the English Lake District red deer, we found only traces of past sika introgression. No sika alleles were detected in the Central Highlands or the Hebridean red deer refugia. We make suggestions for management to prevent further spread of sika alleles into red deer and vice versa.}, } @article {pmid29468029, year = {2018}, author = {Falcón, W and Baxter, RP and Furrer, S and Bauert, M and Hatt, JM and Schaepman-Strub, G and Ozgul, A and Bunbury, N and Clauss, M and Hansen, DM}, title = {Patterns of activity and body temperature of Aldabra giant tortoises in relation to environmental temperature.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2108-2121}, pmid = {29468029}, issn = {2045-7758}, abstract = {We studied the temperature relations of wild and zoo Aldabra giant tortoises (Aldabrachelys gigantea) focusing on (1) the relationship between environmental temperature and tortoise activity patterns (n = 8 wild individuals) and (2) on tortoise body temperature fluctuations, including how their core and external body temperatures vary in relation to different environmental temperature ranges (seasons; n = 4 wild and n = 5 zoo individuals). In addition, we surveyed the literature to review the effect of body mass on core body temperature range in relation to environmental temperature in the Testudinidae. Diurnal activity of tortoises was bimodally distributed and influenced by environmental temperature and season. The mean air temperature at which activity is maximized was 27.9°C, with a range of 25.8-31.7°C. Furthermore, air temperature explained changes in the core body temperature better than did mass, and only during the coldest trial, did tortoises with higher mass show more stable temperatures. Our results, together with the overall Testudinidae overview, suggest that, once variation in environmental temperature has been taken into account, there is little effect of mass on the temperature stability of tortoises. Moreover, the presence of thermal inertia in an individual tortoise depends on the environmental temperatures, and we found no evidence for inertial homeothermy. Finally, patterns of core and external body temperatures in comparison with environmental temperatures suggest that Aldabra giant tortoises act as mixed conformer-regulators. Our study provides a baseline to manage the thermal environment of wild and rewilded populations of an important island ecosystem engineer species in an era of climate change.}, } @article {pmid29468028, year = {2018}, author = {Yuan, Z and Liu, D and Keesing, JK and Zhao, M and Guo, S and Peng, Y and Zhang, H}, title = {Paleoecological evidence for decadal increase in phytoplankton biomass off northwestern Australia in response to climate change.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2097-2107}, pmid = {29468028}, issn = {2045-7758}, abstract = {Ocean warming can modify the phytoplankton biomass on decadal scales. Significant increases in sea surface temperature (SST) and rainfall in the northwest of Australia over recent decades are attributed to climate change. Here, we used four biomarker proxies (TEX86 index, long-chain n-alkanes, brassicasterol, and dinosterol) to reconstruct approximately 60-year variations of SST, terrestrial input, and diatom and dinoflagellate biomass in the coastal waters of the remote Kimberley region. The results showed that the most significant increases in SST and terrestrial input occurred since 1997, accompanied by an abrupt increase in diatom and dinoflagellate biomasses. Compared with the results before 1997, the average TEX86H temperature during 1997-2011 increased approximately 1°C, rainfall increased 248.2 mm, brassicasterol and dinosterol contents increased 8.5 and 1.7 times. Principal component analysis indicated that the warming SST played a more important role in the phytoplankton increase than increased rainfall and river discharge.}, } @article {pmid29468027, year = {2018}, author = {Judson, JLM and Knapp, CR and Welch, ME}, title = {Age-dependent, negative heterozygosity-fitness correlations and local effects in an endangered Caribbean reptile, Iguana delicatissima.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2088-2096}, pmid = {29468027}, issn = {2045-7758}, abstract = {Inbreeding depression can have alarming impacts on threatened species with small population sizes. Assessing inbreeding has therefore become an important focus of conservation research. In this study, heterozygosity-fitness correlations (HFCs) were measured by genotyping 7 loci in 83 adult and 184 hatchling Lesser Antillean Iguanas, Iguana delicatissima, at a communal nesting site in Dominica to assess the role of inbreeding depression on hatchling fitness and recruitment to the adult population in this endangered species. We found insignificant correlations between multilocus heterozygosity and multiple fitness proxies in hatchlings and adults. Further, multilocus heterozygosity did not differ significantly between hatchlings and adults, which suggests that the survivorship of homozygous hatchlings does not differ markedly from that of their heterozygous counterparts. However, genotypes at two individual loci were correlated with hatching date, a finding consistent with the linkage between specific marker loci and segregating deleterious recessive alleles. These results provide only modest evidence that inbreeding depression influences the population dynamics of I. delicatissima on Dominica.}, } @article {pmid29468026, year = {2018}, author = {Pang-Ching, JM and Paxton, KL and Paxton, EH and Pack, AA and Hart, PJ}, title = {The effect of isolation, fragmentation, and population bottlenecks on song structure of a Hawaiian honeycreeper.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2076-2087}, pmid = {29468026}, issn = {2045-7758}, abstract = {Little is known about how important social behaviors such as song vary within and among populations for any of the endemic Hawaiian honeycreepers. Habitat loss and non-native diseases (e.g., avian malaria) have resulted in isolation and fragmentation of Hawaiian honeycreepers within primarily high elevation forests. In this study, we examined how isolation of Hawai'i 'amakihi (Chlorodrepanis virens) populations within a fragmented landscape influences acoustic variability in song. In the last decade, small, isolated populations of disease tolerant 'amakihi have been found within low elevation forests, allowing us to record 'amakihi songs across a large elevational gradient (10-1800 m) that parallels disease susceptibility on Hawai'i island. To understand underlying differences among populations, we examined the role of geographic distance, elevation, and habitat structure on acoustic characteristics of 'amakihi songs. We found that the acoustic characteristics of 'amakihi songs and song-type repertoires varied most strongly across an elevational gradient. Differences in 'amakihi song types were primarily driven by less complex songs (e.g., fewer frequency changes, shorter songs) of individuals recorded at low elevation sites compared to mid and high elevation populations. The reduced complexity of 'amakihi songs at low elevation sites is most likely shaped by the effects of habitat fragmentation and a disease-driven population bottleneck associated with avian malaria, and maintained through isolation, localized song learning and sharing, and cultural drift. These results highlight how a non-native disease through its influence on population demographics may have also indirectly played a role in shaping the acoustic characteristics of a species.}, } @article {pmid29468025, year = {2018}, author = {Laidre, KL and Born, EW and Atkinson, SN and Wiig, Ø and Andersen, LW and Lunn, NJ and Dyck, M and Regehr, EV and McGovern, R and Heagerty, P}, title = {Range contraction and increasing isolation of a polar bear subpopulation in an era of sea-ice loss.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2062-2075}, pmid = {29468025}, issn = {2045-7758}, abstract = {Climate change is expected to result in range shifts and habitat fragmentation for many species. In the Arctic, loss of sea ice will reduce barriers to dispersal or eliminate movement corridors, resulting in increased connectivity or geographic isolation with sweeping implications for conservation. We used satellite telemetry, data from individually marked animals (research and harvest), and microsatellite genetic data to examine changes in geographic range, emigration, and interpopulation connectivity of the Baffin Bay (BB) polar bear (Ursus maritimus) subpopulation over a 25-year period of sea-ice loss. Satellite telemetry collected from n = 43 (1991-1995) and 38 (2009-2015) adult females revealed a significant contraction in subpopulation range size (95% bivariate normal kernel range) in most months and seasons, with the most marked reduction being a 70% decline in summer from 716,000 km2 (SE 58,000) to 211,000 km2 (SE 23,000) (p < .001). Between the 1990s and 2000s, there was a significant shift northward during the on-ice seasons (2.6° shift in winter median latitude, 1.1° shift in spring median latitude) and a significant range contraction in the ice-free summers. Bears in the 2000s were less likely to leave BB, with significant reductions in the numbers of bears moving into Davis Strait (DS) in winter and Lancaster Sound (LS) in summer. Harvest recoveries suggested both short and long-term fidelity to BB remained high over both periods (83-99% of marked bears remained in BB). Genetic analyses using eight polymorphic microsatellites confirmed a previously documented differentiation between BB, DS, and LS; yet weakly differentiated BB from Kane Basin (KB) for the first time. Our results provide the first multiple lines of evidence for an increasingly geographically and functionally isolated subpopulation of polar bears in the context of long-term sea-ice loss. This may be indicative of future patterns for other polar bear subpopulations under climate change.}, } @article {pmid29468024, year = {2018}, author = {Kroeger, SB and Blumstein, DT and Armitage, KB and Reid, JM and Martin, JGA}, title = {Age, state, environment, and season dependence of senescence in body mass.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2050-2061}, pmid = {29468024}, issn = {2045-7758}, abstract = {Senescence is a highly variable process that comprises both age-dependent and state-dependent components and can be greatly affected by environmental conditions. However, few studies have quantified the magnitude of age-dependent and state-dependent senescence in key life-history traits across individuals inhabiting different spatially structured and seasonal environments. We used longitudinal data from wild female yellow-bellied marmots (Marmota flaviventer), living in two adjacent environments that differ in elevation and associated phenology, to quantify how age and individual state, measured as "time to death," affect body mass senescence in different environments. Further, we quantified how patterns of senescence differed between two biologically distinct seasons, spring, and late summer. Body mass senescence had an age-dependent component, expressed as a decrease in mass in old age. Overall, estimated age-dependent senescence was greater in females living in the more favorable lower elevation environment, than in the harsher higher elevation environment, and greater in late summer than in spring. Body mass senescence also had a state-dependent component, captured by effects of time to death, but only in the more favorable lower elevation environment. In spring, body mass gradually decreased from 2 years before death, whereas in late summer, state-dependent effects were expressed as a terminal decrease in body mass in the last year of life. Contrary to expectations, we found that senescence was more likely to be observed under more favorable environmental conditions, rather than under harsher conditions. By further demonstrating that senescence patterns differ among seasons, our results imply that within-year temporal environmental variation must be considered alongside spatial environmental variation in order to characterize and understand the pattern and magnitude of senescence in wild populations.}, } @article {pmid29468023, year = {2018}, author = {Kulmatiski, A}, title = {Community-level plant-soil feedbacks explain landscape distribution of native and non-native plants.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2041-2049}, pmid = {29468023}, issn = {2045-7758}, abstract = {Plant-soil feedbacks (PSFs) have gained attention for their potential role in explaining plant growth and invasion. While promising, most PSF research has measured plant monoculture growth on different soils in short-term, greenhouse experiments. Here, five soil types were conditioned by growing one native species, three non-native species, or a mixed plant community in different plots in a common-garden experiment. After 4 years, plants were removed and one native and one non-native plant community were planted into replicate plots of each soil type. After three additional years, the percentage cover of each of the three target species in each community was measured. These data were used to parameterize a plant community growth model. Model predictions were compared to native and non-native abundance on the landscape. Native community cover was lowest on soil conditioned by the dominant non-native, Centaurea diffusa, and non-native community cover was lowest on soil cultivated by the dominant native, Pseudoroegneria spicata. Consistent with plant growth on the landscape, the plant growth model predicted that the positive PSFs observed in the common-garden experiment would result in two distinct communities on the landscape: a native plant community on native soils and a non-native plant community on non-native soils. In contrast, when PSF effects were removed, the model predicted that non-native plants would dominate all soils, which was not consistent with plant growth on the landscape. Results provide an example where PSF effects were large enough to change the rank-order abundance of native and non-native plant communities and to explain plant distributions on the landscape. The positive PSFs that contributed to this effect reflected the ability of the two dominant plant species to suppress each other's growth. Results suggest that plant dominance, at least in this system, reflects the ability of a species to suppress the growth of dominant competitors through soil-mediated effects.}, } @article {pmid29468022, year = {2018}, author = {García-Roa, R and Sáiz, J and Gómara, B and López, P and Martín, J}, title = {How to tackle chemical communication? Relative proportions versus semiquantitative determination of compounds in lizard chemical secretions.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2032-2040}, pmid = {29468022}, issn = {2045-7758}, abstract = {Knowledge about chemical communication in some vertebrates is still relatively limited. Squamates are a glaring example of this, even when recent evidences indicate that scents are involved in social and sexual interactions. In lizards, where our understanding of chemical communication has considerably progressed in the last few years, many questions about chemical interactions remain unanswered. A potential reason for this is the inherent complexity and technical limitations that some methodologies embody when analyzing the compounds used to convey information. We provide here a straightforward procedure to analyze lizard chemical secretions based on gas chromatography coupled to mass spectrometry that uses an internal standard for the semiquantification of compounds. We compare the results of this method with those obtained by the traditional procedure of calculating relative proportions of compounds. For such purpose, we designed two experiments to investigate if these procedures allowed revealing changes in chemical secretions 1) when lizards received previously a vitamin dietary supplementation or 2) when the chemical secretions were exposed to high temperatures. Our results show that the procedure based on relative proportions is useful to describe the overall chemical profile, or changes in it, at population or species levels. On the other hand, the use of the procedure based on semiquantitative determination can be applied when the target of study is the variation in one or more particular compounds of the sample, as it has proved more accurate detecting quantitative variations in the secretions. This method would reveal new aspects produced by, for example, the effects of different physiological and climatic factors that the traditional method does not show.}, } @article {pmid29468021, year = {2018}, author = {Mejbel, HS and Simons, AM}, title = {Aberrant clones: Birth order generates life history diversity in Greater Duckweed, Spirodela polyrhiza.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2021-2031}, pmid = {29468021}, issn = {2045-7758}, abstract = {Environmental unpredictability is known to result in the evolution of bet-hedging traits. Variable dormancy enhances survival through harsh conditions, and is widely cited as a diversification bet-hedging trait. The floating aquatic plant, Spirodela polyrhiza (Greater Duckweed), provides an opportunity to study diversification because although partially reliable seasonal cues exist, its growing season is subject to an unpredictable and literally "hard" termination when the surface water freezes, and overwinter survival depends on a switch from production of normal daughter fronds to production of dense, sinking "turions" prior to freeze-over. The problem for S. polyrhiza is that diversified dormancy behavior must be generated among clonally produced, genetically identical offspring. Variation in phenology has been observed in the field, but its sources are unknown. Here, we investigate sources of phenological variation in turion production, and test the hypothesis that diversification in turion phenology is generated within genetic lineages through effects of parental birth order. As expected, phenotypic plasticity to temperature is expressed along a thermal gradient; more interestingly, parental birth order was found to have a significant and strong effect on turion phenology: Turions are produced earlier by late birth-order parents. These results hold regardless of whether turion phenology is measured as first turion birth order, time to first turion, or turion frequency. This study addresses a question of current interest on potential mechanisms generating diversification, and suggests that consistent phenotypic differences across birth orders generate life history variation.}, } @article {pmid29468020, year = {2018}, author = {Kinzner, MC and Krapf, P and Nindl, M and Heussler, C and Eisenkölbl, S and Hoffmann, AA and Seeber, J and Arthofer, W and Schlick-Steiner, BC and Steiner, FM}, title = {Life-history traits and physiological limits of the alpine fly Drosophila nigrosparsa (Diptera: Drosophilidae): A comparative study.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {2006-2020}, pmid = {29468020}, issn = {2045-7758}, abstract = {Interspecific variation in life-history traits and physiological limits can be linked to the environmental conditions species experience, including climatic conditions. As alpine environments are particularly vulnerable under climate change, we focus on the montane-alpine fly Drosophila nigrosparsa. Here, we characterized some of its life-history traits and physiological limits and compared these with those of other drosophilids, namely Drosophila hydei, Drosophila melanogaster, and Drosophila obscura. We assayed oviposition rate, longevity, productivity, development time, larval competitiveness, starvation resistance, and heat and cold tolerance. Compared with the other species assayed, D. nigrosparsa is less fecund, relatively long-living, starvation susceptible, cold adapted, and surprisingly well heat adapted. These life-history characteristics provide insights into invertebrate adaptations to alpine conditions which may evolve under ongoing climate change.}, } @article {pmid29468019, year = {2018}, author = {Fernández, CE and Campero, M and Uvo, C and Hansson, LA}, title = {Disentangling population strategies of two cladocerans adapted to different ultraviolet regimes.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {1995-2005}, pmid = {29468019}, issn = {2045-7758}, abstract = {Zooplankton have evolved several mechanisms to deal with environmental threats, such as ultraviolet radiation (UVR), and in order to identify strategies inherent to organisms exposed to different UVR environments, we here examine life-history traits of two lineages of Daphnia pulex. The lineages differed in the UVR dose they had received at their place of origin from extremely high UVR stress at high-altitude Bolivian lakes to low UVR stress near the sea level in temperate Sweden. Nine life-history variables of each lineage were analyzed in laboratory experiments in the presence and the absence of sub-lethal doses of UVR (UV-A band), and we identified trade-offs among variables through structural equation modeling (SEM). The UVR treatment was detrimental to almost all life-history variables of both lineages; however, the Daphnia historically exposed to higher doses of UVR (HighUV) showed a higher overall fecundity than those historically exposed to lower doses of UVR (LowUV). The total offspring and ephippia production, as well as the number of clutches and number of offspring at first reproduction, was directly affected by UVR in both lineages. Main differences between lineages involved indirect effects that affected offspring production as the age at first reproduction. We here show that organisms within the same species have developed different strategies as responses to UVR, although no increased physiological tolerance or plasticity was shown by the HighUV lineage. In addition to known tolerance strategies to UVR, including avoidance, prevention, or repairing of damages, we here propose a population strategy that includes early reproduction and high fertility, which we show compensated for the fitness loss imposed by UVR stress.}, } @article {pmid29468018, year = {2018}, author = {Evans, T and Zu Ermgassen, P and Amano, T and Peh, KS}, title = {Does governance play a role in the distribution of invasive alien species?.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {1984-1994}, pmid = {29468018}, issn = {2045-7758}, abstract = {Invasive alien species (IAS) constitute a major threat to global biological diversity. In order to control their spread, a detailed understanding of the factors influencing their distribution is essential. Although international trade is regarded as a major force structuring spatial patterns of IAS, the role of other social factors remains unclear. Despite studies highlighting the importance of strong governance in slowing drivers of biodiversity loss such as logging, deforestation, and agricultural intensification, no study has yet analyzed its contribution to the issue of IAS. Using estimates of governance quality and comprehensive spatiotemporal IAS data, we performed multiple linear regressions to investigate the effect of governance quality upon the distribution of species listed under "100 of the worst" IAS in 38 Eurasian countries as defined by DASIE. Our model suggested that for countries with higher GDP, stronger governance was associated with a greater number of the worst IAS; in contrast, for the lowest GDP countries under analysis, stronger governance was associated with fewer of these IAS. We elucidate how the quality of governance within a country has implications for trade, tourism, transport, legislation, and economic development, all of which influence the spread of IAS. While our findings support the common assumption that strengthening governance benefits conservation interventions in countries of smaller economy, we find that this effect is not universal. Stronger governance alone cannot adequately address the problem of IAS, and targeted action is required in relatively high-GDP countries in order to stem the influx of IAS associated with high volumes of trade.}, } @article {pmid29468017, year = {2018}, author = {Read, CF and Duncan, DH and Ho, CYC and White, M and Vesk, PA}, title = {Useful surrogates of soil texture for plant ecologists from airborne gamma-ray detection.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {1974-1983}, pmid = {29468017}, issn = {2045-7758}, abstract = {Plant ecologists require spatial information on functional soil properties but are often faced with soil classifications that are not directly interpretable or useful for statistical models. Sand and clay content are important soil properties because they indicate soil water-holding capacity and nutrient content, yet these data are not available for much of the landscape. Remotely sensed soil radiometric data offer promise for developing statistical models of functional soil properties applicable over large areas. Here, we build models linking radiometric data for an area of 40,000 km2 with soil physicochemical data collected over a period of 30 years and demonstrate a strong relationship between gamma radiometric potassium (40K), thorium (²³²Th), and soil sand and clay content. Our models showed predictive performance of 43% with internal cross-validation (to held-out data) and ~30% for external validation to an independent test dataset. This work contributes to broader availability and uptake of remote sensing products for explaining patterns in plant distribution and performance across landscapes.}, } @article {pmid29468016, year = {2018}, author = {Lu, J and Li, SP and Wu, Y and Jiang, L}, title = {Are Hong Kong and Taiwan stepping-stones for invasive species to the mainland of China?.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {1966-1973}, pmid = {29468016}, issn = {2045-7758}, abstract = {Understanding the origins and introduction pathways of invasive species is a fundamental issue for invasion biology, which is necessary for predicting and preventing future invasion. Once an invasive species is established in a new location, this location could serve as a stepping-stone for further invasions. However, such "stepping-stone" effect has not been widely investigated. Using the published literature and records, we compiled the first found locations of 127 top invasive species in China. Our study showed that the most common landing spots of these invasive species were Hong Kong (22 species) and Taiwan (20 species), which accounted for one-third of the invasive species in China. Our analysis revealed that the invasive species in mainland China were more likely to transport from Hong Kong than Macau, a neighboring region with a similar area and colonial history. Similarly, more invasive species were also first landed on Taiwan than Hainan, a nearby island sharing similar climate conditions. Together, our findings indicate that Hong Kong and Taiwan are the most important stepping-stones for invasive species to the mainland of China and suggesting that the increasing trade exchange of China's coastal ports constitutes a potential risk for the spread of more invasive species. We suppose that they would be the future stepping-stones for invasive species to the mainland of China and these coastal ports regions where improved biosecurity is needed now.}, } @article {pmid29468015, year = {2018}, author = {Hsu, YH and Cocroft, RB and Snyder, RL and Lin, CP}, title = {You stay, but I Hop: Host shifting near and far co-dominated the evolution of Enchenopa treehoppers.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {1954-1965}, pmid = {29468015}, issn = {2045-7758}, abstract = {The importance and prevalence of phylogenetic tracking between hosts and dependent organisms caused by co-evolution and shifting between closely related host species have been debated for decades. Most studies of phylogenetic tracking among phytophagous insects and their host plants have been limited to insects feeding on a narrow range of host species. However, narrow host ranges can confound phylogenetic tracking (phylogenetic tracking hypothesis) with host shifting between hosts of intermediate relationship (intermediate hypothesis). Here, we investigated the evolutionary history of the Enchenopa binotata complex of treehoppers. Each species in this complex has high host fidelity, but the entire complex uses hosts across eight plant orders. The phylogenies of E. binotata were reconstructed to evaluate whether (1) tracking host phylogeny; or (2) shifting between intermediately related host plants better explains the evolutionary history of E. binotata. Our results suggest that E. binotata primarily shifted between both distant and intermediate host plants regardless of host phylogeny and less frequently tracked the phylogeny of their hosts. These findings indicate that phytophagous insects with high host fidelity, such as E. binotata, are capable of adaptation not only to closely related host plants but also to novel hosts, likely with diverse phenology and defense mechanisms.}, } @article {pmid29468014, year = {2018}, author = {Zu Dohna, H and Houry, C and Kambris, Z}, title = {A comparative analysis of Wolbachia-induced host reproductive phenotypes reveals transition rate heterogeneity.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {1945-1953}, pmid = {29468014}, issn = {2045-7758}, abstract = {The endosymbiotic bacterium Wolbachia infects a wide range of arthropods and their relatives. It is an intracellular parasite transmitted through the egg from mother to offspring. Wolbachia can spread and persist through various means of host reproductive manipulation. How these different mechanisms of host manipulation evolved in Wolbachia is unclear. Which host reproductive phenotype is most likely to be ancestral and whether evolutionary transitions between some host phenotypes are more common than others remain unanswered questions. Recent studies have revealed multiple cases where the same Wolbachia strain can induce different reproductive phenotypes in different hosts, raising the question to what degree the induced host phenotype should be regarded as a trait of Wolbachia. In this study, we constructed a phylogenetic tree of Wolbachia and analyzed the patterns of host phenotypes along that tree. We were able to detect a phylogenetic signal of host phenotypes on the Wolbachia tree, indicating that the induced host phenotype can be regarded as a Wolbachia trait. However, we found no clear support for the previously stated hypothesis that cytoplasmic incompatibility is ancestral to Wolbachia in arthropods. Our analysis provides evidence for heterogeneous transition rates between host phenotypes.}, } @article {pmid29468013, year = {2018}, author = {Kimball, BA and Alonso-Rodríguez, AM and Cavaleri, MA and Reed, SC and González, G and Wood, TE}, title = {Infrared heater system for warming tropical forest understory plants and soils.}, journal = {Ecology and evolution}, volume = {8}, number = {4}, pages = {1932-1944}, pmid = {29468013}, issn = {2045-7758}, abstract = {The response of tropical forests to global warming is one of the largest uncertainties in predicting the future carbon balance of Earth. To determine the likely effects of elevated temperatures on tropical forest understory plants and soils, as well as other ecosystems, an infrared (IR) heater system was developed to provide in situ warming for the Tropical Responses to Altered Climate Experiment (TRACE) in the Luquillo Experimental Forest in Puerto Rico. Three replicate heated 4-m-diameter plots were warmed to maintain a 4°C increase in understory vegetation compared to three unheated control plots, as sensed by IR thermometers. The equipment was larger than any used previously and was subjected to challenges different from those of many temperate ecosystem warming systems, including frequent power surges and outages, high humidity, heavy rains, hurricanes, saturated clayey soils, and steep slopes. The system was able to maintain the target 4.0°C increase in hourly average vegetation temperatures to within ± 0.1°C. The vegetation was heterogeneous and on a 21° slope, which decreased uniformity of the warming treatment on the plots; yet, the green leaves were fairly uniformly warmed, and there was little difference among 0-10 cm depth soil temperatures at the plot centers, edges, and midway between. Soil temperatures at the 40-50 cm depth increased about 3°C compared to the controls after a month of warming. As expected, the soil in the heated plots dried faster than that of the control plots, but the average soil moisture remained adequate for the plants. The TRACE heating system produced an adequately uniform warming precisely controlled down to at least 50-cm soil depth, thereby creating a treatment that allows for assessing mechanistic responses of tropical plants and soil to warming, with applicability to other ecosystems. No physical obstacles to scaling the approach to taller vegetation (i.e., trees) and larger plots were observed.}, } @article {pmid29467915, year = {2018}, author = {Pandey, AK and Cleary, DW and Laver, JR and Maiden, MCJ and Didelot, X and Gorringe, A and Read, RC}, title = {Correction to: Neisseria lactamica Y92-1009 complete genome sequence.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {4}, pmid = {29467915}, issn = {1944-3277}, abstract = {[This corrects the article DOI: 10.1186/s40793-017-0250-6.].}, } @article {pmid29467296, year = {2018}, author = {Masin, J and Osicka, R and Bumba, L and Sebo, P}, title = {Phospholipase A activity of adenylate cyclase toxin?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2489-E2490}, pmid = {29467296}, issn = {1091-6490}, mesh = {*Adenylate Cyclase Toxin ; Adenylyl Cyclases ; Cholera Toxin ; Enzyme Activation ; Pertussis Toxin ; Phospholipases ; *Virulence Factors, Bordetella ; }, } @article {pmid29467295, year = {2018}, author = {Ostolaza, H}, title = {Reply to Masin et al: To be or not to be a phospholipase A.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2491}, pmid = {29467295}, issn = {1091-6490}, mesh = {*Phospholipases ; }, } @article {pmid29467294, year = {2018}, author = {Kardos, M and Nietlisbach, P and Hedrick, PW}, title = {How should we compare different genomic estimates of the strength of inbreeding depression?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2492-E2493}, pmid = {29467294}, issn = {1091-6490}, mesh = {Consanguinity ; *Genomics ; *Inbreeding Depression ; }, } @article {pmid29467293, year = {2018}, author = {Yengo, L and Zhu, Z and Wray, NR and Weir, BS and Yang, J and Robinson, MR and Visscher, PM}, title = {Reply to Kardos et al.: Estimation of inbreeding depression from SNP data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2494-E2495}, pmid = {29467293}, issn = {1091-6490}, support = {R01 GM075091/GM/NIGMS NIH HHS/United States ; }, mesh = {Consanguinity ; *Inbreeding Depression ; *Pedigree ; }, } @article {pmid29467292, year = {2018}, author = {Sanders, D and Thébault, E and Kehoe, R and Frank van Veen, FJ}, title = {Trophic redundancy reduces vulnerability to extinction cascades.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2419-2424}, pmid = {29467292}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; Ecology ; *Ecosystem ; *Extinction, Biological ; *Food Chain ; Humans ; Models, Theoretical ; Wasps/physiology ; }, abstract = {Current species extinction rates are at unprecedentedly high levels. While human activities can be the direct cause of some extinctions, it is becoming increasingly clear that species extinctions themselves can be the cause of further extinctions, since species affect each other through the network of ecological interactions among them. There is concern that the simplification of ecosystems, due to the loss of species and ecological interactions, increases their vulnerability to such secondary extinctions. It is predicted that more complex food webs will be less vulnerable to secondary extinctions due to greater trophic redundancy that can buffer against the effects of species loss. Here, we demonstrate in a field experiment with replicated plant-insect communities, that the probability of secondary extinctions is indeed smaller in food webs that include trophic redundancy. Harvesting one species of parasitoid wasp led to secondary extinctions of other, indirectly linked, species at the same trophic level. This effect was markedly stronger in simple communities than for the same species within a more complex food web. We show that this is due to functional redundancy in the more complex food webs and confirm this mechanism with a food web simulation model by highlighting the importance of the presence and strength of trophic links providing redundancy to those links that were lost. Our results demonstrate that biodiversity loss, leading to a reduction in redundant interactions, can increase the vulnerability of ecosystems to secondary extinctions, which, when they occur, can then lead to further simplification and run-away extinction cascades.}, } @article {pmid29467291, year = {2018}, author = {Xie, K and Ryan, DP and Pearson, BL and Henzel, KS and Neff, F and Vidal, RO and Hennion, M and Lehmann, I and Schleif, M and Schröder, S and Adler, T and Rathkolb, B and Rozman, J and Schütz, AL and Prehn, C and Mickael, ME and Weiergräber, M and Adamski, J and Busch, DH and Ehninger, G and Matynia, A and Jackson, WS and Wolf, E and Fuchs, H and Gailus-Durner, V and Bonn, S and Hrabě de Angelis, M and Ehninger, D}, title = {Epigenetic alterations in longevity regulators, reduced life span, and exacerbated aging-related pathology in old father offspring mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2348-E2357}, pmid = {29467291}, issn = {1091-6490}, mesh = {Age Factors ; Aging/*genetics/physiology ; Animals ; DNA Methylation ; *Epigenesis, Genetic ; Fathers ; Female ; Humans ; Life Expectancy ; *Longevity ; Male ; Mechanistic Target of Rapamycin Complex 1/genetics/metabolism ; Mice ; Pedigree ; Promoter Regions, Genetic ; Spermatozoa/metabolism ; }, abstract = {Advanced age is not only a major risk factor for a range of disorders within an aging individual but may also enhance susceptibility for disease in the next generation. In humans, advanced paternal age has been associated with increased risk for a number of diseases. Experiments in rodent models have provided initial evidence that paternal age can influence behavioral traits in offspring animals, but the overall scope and extent of paternal age effects on health and disease across the life span remain underexplored. Here, we report that old father offspring mice showed a reduced life span and an exacerbated development of aging traits compared with young father offspring mice. Genome-wide epigenetic analyses of sperm from aging males and old father offspring tissue identified differentially methylated promoters, enriched for genes involved in the regulation of evolutionarily conserved longevity pathways. Gene expression analyses, biochemical experiments, and functional studies revealed evidence for an overactive mTORC1 signaling pathway in old father offspring mice. Pharmacological mTOR inhibition during the course of normal aging ameliorated many of the aging traits that were exacerbated in old father offspring mice. These findings raise the possibility that inherited alterations in longevity pathways contribute to intergenerational effects of aging in old father offspring mice.}, } @article {pmid29467290, year = {2018}, author = {Grosholz, ED}, title = {New sources for the emergence of new invaders.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2270-2271}, pmid = {29467290}, issn = {1091-6490}, mesh = {*Ecosystem ; *Introduced Species ; }, } @article {pmid29467289, year = {2018}, author = {Buyan, A and Sun, D and Corry, B}, title = {Protonation state of inhibitors determines interaction sites within voltage-gated sodium channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {E3135-E3144}, pmid = {29467289}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Binding Sites ; Biological Transport ; Humans ; Ion Channel Gating/*physiology ; Molecular Dynamics Simulation ; Protons ; Sequence Homology ; Sodium Channel Blockers/*chemistry/*metabolism ; Voltage-Gated Sodium Channels/*chemistry/*metabolism ; }, abstract = {Voltage-gated sodium channels are essential for carrying electrical signals throughout the body, and mutations in these proteins are responsible for a variety of disorders, including epilepsy and pain syndromes. As such, they are the target of a number of drugs used for reducing pain or combatting arrhythmias and seizures. However, these drugs affect all sodium channel subtypes found in the body. Designing compounds to target select sodium channel subtypes will provide a new therapeutic pathway and would maximize treatment efficacy while minimizing side effects. Here, we examine the binding preferences of nine compounds known to be sodium channel pore blockers in molecular dynamics simulations. We use the approach of replica exchange solute tempering (REST) to gain a more complete understanding of the inhibitors' behavior inside the pore of NavMs, a bacterial sodium channel, and NavPas, a eukaryotic sodium channel. Using these simulations, we are able to show that both charged and neutral compounds partition into the bilayer, but neutral forms more readily cross it. We show that there are two possible binding sites for the compounds: (i) a site on helix 6, which has been previously determined by many experimental and computational studies, and (ii) an additional site, occupied by protonated compounds in which the positively charged part of the drug is attracted into the selectivity filter. Distinguishing distinct binding poses for neutral and charged compounds is essential for understanding the nature of pore block and will aid the design of subtype-selective sodium channel inhibitors.}, } @article {pmid29467288, year = {2018}, author = {Ohhashi, Y and Yamaguchi, Y and Kurahashi, H and Kamatari, YO and Sugiyama, S and Uluca, B and Piechatzek, T and Komi, Y and Shida, T and Müller, H and Hanashima, S and Heise, H and Kuwata, K and Tanaka, M}, title = {Molecular basis for diversification of yeast prion strain conformation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2389-2394}, pmid = {29467288}, issn = {1091-6490}, mesh = {*Amyloid/chemistry/metabolism ; Kinetics ; Nuclear Magnetic Resonance, Biomolecular ; *Peptide Termination Factors/chemistry/genetics/metabolism ; *Prions/chemistry/genetics/metabolism ; Protein Conformation ; Protein Folding ; *Saccharomyces cerevisiae Proteins/chemistry/genetics/metabolism ; }, abstract = {Self-propagating β-sheet-rich fibrillar protein aggregates, amyloid fibers, are often associated with cellular dysfunction and disease. Distinct amyloid conformations dictate different physiological consequences, such as cellular toxicity. However, the origin of the diversity of amyloid conformation remains unknown. Here, we suggest that altered conformational equilibrium in natively disordered monomeric proteins leads to the adaptation of alternate amyloid conformations that have different phenotypic effects. We performed a comprehensive high-resolution structural analysis of Sup35NM, an N-terminal fragment of the Sup35 yeast prion protein, and found that monomeric Sup35NM harbored latent local compact structures despite its overall disordered conformation. When the hidden local microstructures were relaxed by genetic mutations or solvent conditions, Sup35NM adopted a strikingly different amyloid conformation, which redirected chaperone-mediated fiber fragmentation and modulated prion strain phenotypes. Thus, dynamic conformational fluctuations in natively disordered monomeric proteins represent a posttranslational mechanism for diversification of aggregate structures and cellular phenotypes.}, } @article {pmid29467287, year = {2018}, author = {Forester, CM and Zhao, Q and Phillips, NJ and Urisman, A and Chalkley, RJ and Oses-Prieto, JA and Zhang, L and Ruggero, D and Burlingame, AL}, title = {Revealing nascent proteomics in signaling pathways and cell differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2353-2358}, pmid = {29467287}, issn = {1091-6490}, support = {P41 GM103481/GM/NIGMS NIH HHS/United States ; R01 CA140456/CA/NCI NIH HHS/United States ; R01 CA154916/CA/NCI NIH HHS/United States ; S10 OD016229/OD/NIH HHS/United States ; R01 CA184624/CA/NCI NIH HHS/United States ; K12 HD072222/HD/NICHD NIH HHS/United States ; T32 CA128583/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Differentiation/*physiology ; Chromatography, Liquid ; Drug Discovery ; Humans ; K562 Cells ; Protein Biosynthesis ; Proteome/*analysis/chemistry/metabolism ; Proteomics/*methods ; Puromycin/analogs & derivatives ; Signal Transduction/*physiology ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; Tandem Mass Spectrometry ; }, abstract = {Regulation of gene expression at the level of protein synthesis is a crucial element in driving how the genetic landscape is expressed. However, we are still limited in technologies that can quantitatively capture the immediate proteomic changes that allow cells to respond to specific stimuli. Here, we present a method to capture and identify nascent proteomes in situ across different cell types without disturbing normal growth conditions, using O-propargyl-puromycin (OPP). Cell-permeable OPP rapidly labels nascent elongating polypeptides, which are subsequently conjugated to biotin-azide, using click chemistry, and captured with streptavidin beads, followed by digestion and analysis, using liquid chromatography-tandem mass spectrometry. Our technique of OPP-mediated identification (OPP-ID) allows detection of widespread proteomic changes within a short 2-hour pulse of OPP. We illustrate our technique by recapitulating alterations of proteomic networks induced by a potent mammalian target of rapamycin inhibitor, MLN128. In addition, by employing OPP-ID, we identify more than 2,100 proteins and uncover distinct protein networks underlying early erythroid progenitor and differentiation states not amenable to alternative approaches such as amino acid analog labeling. We present OPP-ID as a method to quantitatively identify nascent proteomes across an array of biological contexts while preserving the subtleties directing signaling in the native cellular environment.}, } @article {pmid29467286, year = {2018}, author = {Altindis, E and Cai, W and Sakaguchi, M and Zhang, F and GuoXiao, W and Liu, F and De Meyts, P and Gelfanov, V and Pan, H and DiMarchi, R and Kahn, CR}, title = {Viral insulin-like peptides activate human insulin and IGF-1 receptor signaling: A paradigm shift for host-microbe interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2461-2466}, pmid = {29467286}, issn = {1091-6490}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; R01 DK031036/DK/NIDDK NIH HHS/United States ; R01 DK033201/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; Cell Proliferation ; Glucose/metabolism ; Hepatocytes ; Host-Pathogen Interactions/*physiology ; Humans ; Insulin/genetics/*metabolism ; Insulin-Like Growth Factor I/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Receptor, IGF Type 1/*metabolism ; Signal Transduction ; Viral Proteins/genetics/*metabolism ; Virus Diseases/virology ; Viruses/*genetics ; }, abstract = {Viruses are the most abundant biological entities and carry a wide variety of genetic material, including the ability to encode host-like proteins. Here we show that viruses carry sequences with significant homology to several human peptide hormones including insulin, insulin-like growth factors (IGF)-1 and -2, FGF-19 and -21, endothelin-1, inhibin, adiponectin, and resistin. Among the strongest homologies were those for four viral insulin/IGF-1-like peptides (VILPs), each encoded by a different member of the family Iridoviridae VILPs show up to 50% homology to human insulin/IGF-1, contain all critical cysteine residues, and are predicted to form similar 3D structures. Chemically synthesized VILPs can bind to human and murine IGF-1/insulin receptors and stimulate receptor autophosphorylation and downstream signaling. VILPs can also increase glucose uptake in adipocytes and stimulate the proliferation of fibroblasts, and injection of VILPs into mice significantly lowers blood glucose. Transfection of mouse hepatocytes with DNA encoding a VILP also stimulates insulin/IGF-1 signaling and DNA synthesis. Human microbiome studies reveal the presence of these Iridoviridae in blood and fecal samples. Thus, VILPs are members of the insulin/IGF superfamily with the ability to be active on human and rodent cells, raising the possibility for a potential role of VILPs in human disease. Furthermore, since only 2% of viruses have been sequenced, this study raises the potential for discovery of other viral hormones which, along with known virally encoded growth factors, may modify human health and disease.}, } @article {pmid29467285, year = {2018}, author = {Man, HSJ and Sukumar, AN and Lam, GC and Turgeon, PJ and Yan, MS and Ku, KH and Dubinsky, MK and Ho, JJD and Wang, JJ and Das, S and Mitchell, N and Oettgen, P and Sefton, MV and Marsden, PA}, title = {Angiogenic patterning by STEEL, an endothelial-enriched long noncoding RNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2401-2406}, pmid = {29467285}, issn = {1091-6490}, support = {MOP 142307//CIHR/Canada ; }, mesh = {Animals ; Cells, Cultured ; Chromatin/*metabolism ; *Endothelial Cells/cytology/metabolism ; Endothelium, Vascular/cytology ; Hemodynamics ; Human Umbilical Vein Endothelial Cells ; Humans ; Mice ; Mice, SCID ; *Neovascularization, Physiologic/genetics/physiology ; *RNA, Long Noncoding/genetics/metabolism ; }, abstract = {Endothelial cell (EC)-enriched protein coding genes, such as endothelial nitric oxide synthase (eNOS), define quintessential EC-specific physiologic functions. It is not clear whether long noncoding RNAs (lncRNAs) also define cardiovascular cell type-specific phenotypes, especially in the vascular endothelium. Here, we report the existence of a set of EC-enriched lncRNAs and define a role for spliced-transcript endothelial-enriched lncRNA (STEEL) in angiogenic potential, macrovascular/microvascular identity, and shear stress responsiveness. STEEL is expressed from the terminus of the HOXD locus and is transcribed antisense to HOXD transcription factors. STEEL RNA increases the number and integrity of de novo perfused microvessels in an in vivo model and augments angiogenesis in vitro. The STEEL RNA is polyadenylated, nuclear enriched, and has microvascular predominance. Functionally, STEEL regulates a number of genes in diverse ECs. Of interest, STEEL up-regulates both eNOS and the transcription factor Kruppel-like factor 2 (KLF2), and is subject to feedback inhibition by both eNOS and shear-augmented KLF2. Mechanistically, STEEL up-regulation of eNOS and KLF2 is transcriptionally mediated, in part, via interaction of chromatin-associated STEEL with the poly-ADP ribosylase, PARP1. For instance, STEEL recruits PARP1 to the KLF2 promoter. This work identifies a role for EC-enriched lncRNAs in the phenotypic adaptation of ECs to both body position and hemodynamic forces and establishes a newer role for lncRNAs in the transcriptional regulation of EC identity.}, } @article {pmid29467284, year = {2018}, author = {Grelat, A and Benoit, L and Wagner, S and Moigneu, C and Lledo, PM and Alonso, M}, title = {Adult-born neurons boost odor-reward association.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2514-2519}, pmid = {29467284}, issn = {1091-6490}, mesh = {Animals ; Discrimination Learning/*physiology ; Female ; Male ; Models, Neurological ; Odorants ; *Olfactory Bulb/cytology/physiology ; Olfactory Receptor Neurons/*physiology ; Rats ; *Reward ; Smell/*physiology ; }, abstract = {Olfaction is an important sensory modality driving fundamental behaviors. During odor-dependent learning, a positive value is commonly assigned to an odorant, and multiple forms of plasticity are involved when such odor-reward associations are formed. In rodents, one of the mechanisms underlying plasticity in the olfactory bulb consists in recruiting new neurons daily throughout life. However, it is still unknown whether adult-born neurons might participate in encoding odor value. Here, we demonstrate that exposure to reward-associated odors specifically increases activity of adult-born neurons but not preexisting neurons. Remarkably, adult-born neuron activation during rewarded odor presentation heightens discrimination learning and enhances the ability to update the odor value during reversal association. Moreover, in some cases, activation of this interneuron population can trigger olfactory learning without sensory stimulation. Taken together, our results show a specific involvement of adult-born neurons in facilitating odor-reward association during adaptive learning.}, } @article {pmid29467032, year = {2018}, author = {Stark, C and Taimen, P and Savunen, T and Koskenvuo, J}, title = {Pegylated and liposomal doxorubicin is associated with high mortality and causes limited cardiotoxicity in mice.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {148}, pmid = {29467032}, issn = {1756-0500}, mesh = {Animals ; Cardiomyopathies/*chemically induced/*prevention & control ; Cardiotoxicity/*prevention & control ; Disease Models, Animal ; Doxorubicin/administration & dosage/*analogs & derivatives/toxicity ; Electrocardiography ; Male ; Mice ; Polyethylene Glycols/administration & dosage/toxicity ; Thymosin/*pharmacology ; }, abstract = {OBJECTIVE: We wanted to determine the impact of different doses of a pegylated and liposomal formulation of the cardiotoxic drug doxorubicin on cardiac function, fibrosis and survival in mice. The drug causes myocardial damage by producing reactive oxygen species, mitochondrial damage and lipid peroxidation. Thymosin beta 4 is a peptide with cardioprotective, anti-oxidant and anti-fibrotic properties and we further investigated whether the peptide could attenuate this drug-induced injury by measuring cardiac function and fibrosis.

RESULTS: Mice receiving high doses of doxorubicin died early during follow-up. Lowering the dose improved survival but did not markedly impair cardiac function on echocardiography and caused only limited fibrosis on histology. Thymosin beta 4 had only a mild protective effect on early cardiac function and did not significantly influence myocardial fibrosis. In conclusion, the use of pegylated and liposomal doxorubicin was not appropriate for inducing experimental cardiomyopathy. Thymosin beta 4 therapy was not beneficial in this setting.}, } @article {pmid29467031, year = {2018}, author = {Rapp, DE and Colhoun, A and Morin, J and Bradford, TJ}, title = {Assessment of communication technology and post-operative telephone surveillance during global urology mission.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {149}, pmid = {29467031}, issn = {1756-0500}, mesh = {Adult ; *Aftercare ; Aged ; Aged, 80 and over ; Belize ; *Electronic Mail/standards/statistics & numerical data ; Female ; Humans ; *Internet/standards/statistics & numerical data ; Male ; *Medical Missions ; Middle Aged ; *Physician-Patient Relations ; Postoperative Period ; *Telemedicine ; *Telephone/standards/statistics & numerical data ; United States ; *Urologic Surgical Procedures ; Young Adult ; }, abstract = {OBJECTIVE: Compliance with post-operative follow-up in the context of international surgical trips is often poor. The etiology of this problem is multifactorial and includes lack of local physician involvement, transportation costs, and work responsibilities. We aimed to better understand availability of communication technologies within Belize and use this information to improve follow-up after visiting surgical trips to a public hospital in Belize City. Accordingly, a 6-item questionnaire assessing access to communication technologies was completed by all patients undergoing evaluation by a visiting surgical team in 2014. Based on this data, a pilot program for patients undergoing surgery was instituted for subsequent missions (2015-2016) that included a 6-week post-operative telephone interview with a visiting physician located in the United States.

RESULTS: Fifty-four (n = 54) patients were assessed via survey with 89% responding that they had a mobile phone. Patients reported less access to home internet (59%), local internet (52%), and email (48%). Of 35 surgical patients undergoing surgery during 2 subsequent surgical trips, 18 (51%) were compliant with telephone interview at 6-week follow-up. Issues were identified in 3 (17%) patients that allowed for physician assistance. The cost per patient interview was $10 USD.}, } @article {pmid29467028, year = {2018}, author = {Estrada-Rojo, F and Morales-Gomez, J and Coballase-Urrutia, E and Martinez-Vargas, M and Navarro, L}, title = {Diurnal variation of NMDA receptor expression in the rat cerebral cortex is associated with traumatic brain injury damage.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {150}, pmid = {29467028}, issn = {1756-0500}, support = {152510//CONACYT/ ; IG201014//PAPIIT/ ; IN223417//PAPIIT/ ; }, mesh = {Animals ; Brain Injuries, Traumatic/*metabolism/*physiopathology ; Circadian Rhythm/*physiology ; Disease Models, Animal ; Male ; Motor Cortex/*injuries/*metabolism/*physiopathology ; Rats ; Rats, Wistar ; Receptors, N-Methyl-D-Aspartate/*metabolism ; Time Factors ; }, abstract = {OBJECTIVE: Data from our laboratory suggest that recovery from a traumatic brain injury depends on the time of day at which it occurred. In this study, we examined whether traumatic brain injury -induced damage is related to circadian variation in N-methyl-D-aspartate receptor expression in rat cortex.

RESULTS: We confirmed that traumatic brain injury recovery depended on the time of day at which the damage occurred. We also found that motor cortex N-methyl-D-aspartate receptor subunit NR1 expression exhibited diurnal variation in both control and traumatic brain injury-subjected rats. However, this rhythm is more pronounced in traumatic brain injury-subjected rats, with minimum expression in those injured during nighttime hours. These findings suggest that traumatic brain injury occurrence times should be considered in future clinical studies and when designing neuroprotective strategies for patients.}, } @article {pmid29466995, year = {2018}, author = {Greaves, M}, title = {Nothing in cancer makes sense except….}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {22}, pmid = {29466995}, issn = {1741-7007}, support = {105104/Z/14/Z//Wellcome Trust/United Kingdom ; }, abstract = {Paraphrasing Dobzhansky's famous dictum, I discuss how interrogating cancer through the lens of evolution has transformed our understanding of its development, causality and treatment resistance. The emerging picture of cancer captures its extensive diversity and therapeutic resilience, highlighting the need for more innovative approaches to control.}, } @article {pmid29466976, year = {2018}, author = {Ma, B and Sun, J}, title = {Predicting the distribution of Stipa purpurea across the Tibetan Plateau via the MaxEnt model.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {10}, pmid = {29466976}, issn = {1472-6785}, support = {2016YFC0502002//State Key Research Development Program of China/International ; 2016YFC0501803//State Key Research Development Program of China/International ; 2016YFC0501802//State Key Research Development Program of China/International ; }, abstract = {BACKGROUND: The ecosystems across Tibetan Plateau are changing rapidly under the influence of climate warming, which has caused substantial changes in spatial and temporal environmental patterns. Stipa purpurea, as a dominant herbsage resource in alpine steppe, has a great influence on animal husbandry in the Tibetan Plateau. Global warming has been forecasted to continue in the future (2050s, 2070s), questioning the future distribution of S. purpurea and its response to climate change. The maximum entropy (MaxEnt) modeling, due to its multiple advantages (e.g. uses presence-only data, performs well with incomplete data, and requires small sample sizes and gaps), has been used to understand species environment relationships and predict species distributions across locations that have not been sampled.

RESULTS: Annual mean temperature, annual precipitation, temperature seasonality, altitude, and precipitation during the driest month, significantly affected the distribution of S. purpurea. Only 0.70% of the Tibetan Plateau area included a very highly suitable habitat (habitat suitability [HS] = 0.8-1.0). Highly suitable habitat (HS = 0.6-0.8), moderately suitable habitat (HS = 0.4-0.6), and unsuitable habitat (HS = 0.2-0.4) occupied 6.20, 14.30 and 22.40% of the Tibetan Plateau area, respectively, and the majority (56.40%) of the Tibetan Plateau area constituted a highly unsuitable habitat (HS = 0-0.2). In addition, the response curves of species ecological suitability simulated by generalized additive model nearly corresponded with the response curves generated by the MaxEnt model.

CONCLUSIONS: At a temporal scale, the habitat suitability of S. purpurea tends to increase from the 1990s to 2050s, but decline from the 2050s to 2070s. At a spatial scale, the future distribution of S. purpurea will not exhibit sweeping changes and will remain in the central and southeastern regions of the Tibetan Plateau. These results benefit the local animal husbandry and provide evidence for establishing reasonable management practices.}, } @article {pmid29466945, year = {2018}, author = {Pisupati, R and Vergara, D and Kane, NC}, title = {Diversity and evolution of the repetitive genomic content in Cannabis sativa.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {156}, pmid = {29466945}, issn = {1471-2164}, mesh = {Cannabis/*genetics ; DNA, Plant ; DNA, Ribosomal ; *Evolution, Molecular ; *Genetic Variation ; *Genome, Plant ; High-Throughput Nucleotide Sequencing/*methods ; Humulus/genetics ; Morus/genetics ; *Repetitive Sequences, Nucleic Acid ; Retroelements ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: The repetitive content of the genome, once considered to be "junk DNA", is in fact an essential component of genomic architecture and evolution. In this study, we used the genomes of three varieties of Cannabis sativa, three varieties of Humulus lupulus and one genotype of Morus notabilis to explore their repetitive content using a graph-based clustering method, designed to explore and compare repeat content in genomes that have not been fully assembled.

RESULTS: The repetitive content in the C. sativa genome is mainly composed of the retrotransposons LTR/Copia and LTR/Gypsy (14% and 14.8%, respectively), ribosomal DNA (2%), and low-complexity sequences (29%). We observed a recent copy number expansion in some transposable element families. Simple repeats and low complexity regions of the genome show higher intra and inter species variation.

CONCLUSIONS: As with other sequenced genomes, the repetitive content of C. sativa's genome exhibits a wide range of evolutionary patterns. Some repeat types have patterns of diversity consistent with expansions followed by losses in copy number, while others may have expanded more slowly and reached a steady state. Still, other repetitive sequences, particularly ribosomal DNA (rDNA), show signs of concerted evolution playing a major role in homogenizing sequence variation.}, } @article {pmid29466943, year = {2018}, author = {Paolacci, AR and Catarcione, G and Ederli, L and Zadra, C and Pasqualini, S and Badiani, M and Musetti, R and Santi, S and Ciaffi, M}, title = {Correction to: Jasmonate-mediated defence responses, unlike salicylate-mediated responses, are involved in the recovery of grapevine from bois noir disease.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {39}, pmid = {29466943}, issn = {1471-2229}, abstract = {CORRECTION: Following publication of the original article [1], it came to the attention of the authors that they had omitted to acknowledge the University of Parma. The Acknowledgement section should read as follows: "The authors kindly acknowledge the University of Parma (Department of Chemistry, Life Sciences and Environmental Sustainability; formerly Department of Life Sciences/Evolutionary and Functional Biology) for the transfer of funds obtained from the Ager project: GIALLUMI DELLA VITE: TECNOLOGIE INNOVATIVE PER LA DIAGNOSI E LO STUDIO DELLE INTERAZIONI PIANTA/PATOGENO, BANDO AGER VITICOLTURA DA VINO".}, } @article {pmid29466942, year = {2018}, author = {Liu, Y and Koh, CMJ and Yap, SA and Du, M and Hlaing, MM and Ji, L}, title = {Identification of novel genes in the carotenogenic and oleaginous yeast Rhodotorula toruloides through genome-wide insertional mutagenesis.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {14}, pmid = {29466942}, issn = {1471-2180}, abstract = {BACKGROUND: Rhodotorula toruloides is an outstanding producer of lipids and carotenoids. Currently, information on the key metabolic pathways and their molecular basis of regulation remains scarce, severely limiting efforts to engineer it as an industrial host.

RESULTS: We have adapted Agrobacterium tumefaciens-mediated transformation (ATMT) as a gene-tagging tool for the identification of novel genes in R. toruloides. Multiple factors affecting transformation efficiency in several species in the Pucciniomycotina subphylum were optimized. The Agrobacterium transfer DNA (T-DNA) showed predominantly single-copy chromosomal integrations in R. toruloides, which were trackable by high efficiency thermal asymmetric interlaced PCR (hiTAIL-PCR). To demonstrate the application of random T-DNA insertions for strain improvement and gene hunting, 3 T-DNA insertional libraries were screened against cerulenin, nile red and tetrazolium violet respectively, resulting in the identification of 22 mutants with obvious phenotypes in fatty acid or lipid metabolism. Similarly, 5 carotenoid biosynthetic mutants were obtained through visual screening of the transformants. To further validate the gene tagging strategy, one of the carotenoid production mutants, RAM5, was analyzed in detail. The mutant had a T-DNA inserted at the putative phytoene desaturase gene CAR1. Deletion of CAR1 by homologous recombination led to a phenotype similar to RAM5 and it could be genetically complemented by re-introduction of the wild-type CAR1 genome sequence.

CONCLUSIONS: T-DNA insertional mutagenesis is an efficient forward genetic tool for gene discovery in R. toruloides and related oleaginous yeast species. It is also valuable for metabolic engineering in these hosts. Further analysis of the 27 mutants identified in this study should augment our knowledge of the lipid and carotenoid biosynthesis, which may be exploited for oil and isoprenoid metabolic engineering.}, } @article {pmid29466941, year = {2018}, author = {Meers, MP and Adelman, K and Duronio, RJ and Strahl, BD and McKay, DJ and Matera, AG}, title = {Transcription start site profiling uncovers divergent transcription and enhancer-associated RNAs in Drosophila melanogaster.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {157}, pmid = {29466941}, issn = {1471-2164}, support = {F31 CA177088/CA/NCI NIH HHS/United States ; R01 DA036897/DA/NIDA NIH HHS/United States ; T32 GM007092/GM/NIGMS NIH HHS/United States ; R01-DA036897//NIH Office of the Director/International ; }, mesh = {Animals ; Computational Biology/methods ; Drosophila melanogaster/*genetics ; *Enhancer Elements, Genetic ; Gene Expression Profiling/methods ; Gene Expression Regulation ; Nucleosomes ; Promoter Regions, Genetic ; RNA/*genetics ; *Transcription Initiation Site ; Transcription, Genetic ; }, abstract = {BACKGROUND: High-resolution transcription start site (TSS) mapping in D. melanogaster embryos and cell lines has revealed a rich and detailed landscape of both cis- and trans-regulatory elements and factors. However, TSS profiling has not been investigated in an orthogonal in vivo setting. Here, we present a comprehensive dataset that links TSS dynamics with nucleosome occupancy and gene expression in the wandering third instar larva, a developmental stage characterized by large-scale shifts in transcriptional programs in preparation for metamorphosis.

RESULTS: The data recapitulate major regulatory classes of TSSs, based on peak width, promoter-proximal polymerase pausing, and cis-regulatory element density. We confirm the paucity of divergent transcription units in D. melanogaster, but also identify notable exceptions. Furthermore, we identify thousands of novel initiation events occurring at unannotated TSSs that can be classified into functional categories by their local density of histone modifications. Interestingly, a sub-class of these unannotated TSSs overlaps with functionally validated enhancer elements, consistent with a regulatory role for "enhancer RNAs" (eRNAs) in defining developmental transcription programs.

CONCLUSIONS: High-depth TSS mapping is a powerful strategy for identifying and characterizing low-abundance and/or low-stability RNAs. Global analysis of transcription initiation patterns in a developing organism reveals a vast number of novel initiation events that identify potential eRNAs as well as other non-coding transcripts critical for animal development.}, } @article {pmid29466940, year = {2018}, author = {Ivády, G and Madar, L and Dzsudzsák, E and Koczok, K and Kappelmayer, J and Krulisova, V and Macek, M and Horváth, A and Balogh, I}, title = {Analytical parameters and validation of homopolymer detection in a pyrosequencing-based next generation sequencing system.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {158}, pmid = {29466940}, issn = {1471-2164}, support = {K109076//Országos Tudományos Kutatási Alapprogramok/International ; 00064203//Ministerstvo Zdravotnictví Ceské Republiky/International ; CZ.2.16/3.1.00/24022OPPK//European Regional Development Fund Prague/International ; NF-CZ11-PDP-3-003-2014, LM2015091 and COST-LD14073//Norway Grants/International ; UNKP-16-3 IV/4//New National Excellence Program of the Ministry of Human Capacities/International ; GINOP-2.3.2-15-2016-00039//Ministry of National Economy, Hungary/International ; }, mesh = {Cystic Fibrosis/*genetics ; Cystic Fibrosis Transmembrane Conductance Regulator/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Plasmids ; Sequence Analysis, DNA/*methods ; *Tandem Repeat Sequences ; }, abstract = {BACKGROUND: Current technologies in next-generation sequencing are offering high throughput reads at low costs, but still suffer from various sequencing errors. Although pyro- and ion semiconductor sequencing both have the advantage of delivering long and high quality reads, problems might occur when sequencing homopolymer-containing regions, since the repeating identical bases are going to incorporate during the same synthesis cycle, which leads to uncertainty in base calling. The aim of this study was to evaluate the analytical performance of a pyrosequencing-based next-generation sequencing system in detecting homopolymer sequences using homopolymer-preintegrated plasmid constructs and human DNA samples originating from patients with cystic fibrosis.

RESULTS: In the plasmid system average correct genotyping was 95.8% in 4-mers, 87.4% in 5-mers and 72.1% in 6-mers. Despite the experienced low genotyping accuracy in 5- and 6-mers, it was possible to generate amplicons with more than a 90% adequate detection rate in every homopolymer tract. When homopolymers in the CFTR gene were sequenced average accuracy was 89.3%, but varied in a wide range (52.2 - 99.1%). In all but one case, an optimal amplicon-sequencing primer combination could be identified. In that single case (7A tract in exon 14 (c.2046_2052)), none of the tested primer sets produced the required analytical performance.

CONCLUSIONS: Our results show that pyrosequencing is the most reliable in case of 4-mers and as homopolymer length gradually increases, accuracy deteriorates. With careful primer selection, the NGS system was able to correctly genotype all but one of the homopolymers in the CFTR gene. In conclusion, we configured a plasmid test system that can be used to assess genotyping accuracy of NGS devices and developed an accurate NGS assay for the molecular diagnosis of CF using self-designed primers for amplification and sequencing.}, } @article {pmid29466603, year = {2018}, author = {Rollinson, N and Rowe, L}, title = {Temperature-dependent oxygen limitation and the rise of Bergmann's rule in species with aquatic respiration.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {977-988}, doi = {10.1111/evo.13458}, pmid = {29466603}, issn = {1558-5646}, abstract = {Bergmann's rule is the propensity for species-mean body size to decrease with increasing temperature. Temperature-dependent oxygen limitation has been hypothesized to help drive temperature-size relationships among ectotherms, including Bergmann's rule, where organisms reduce body size under warm oxygen-limited conditions, thereby maintaining aerobic scope. Temperature-dependent oxygen limitation should be most pronounced among aquatic ectotherms that cannot breathe aerially, as oxygen solubility in water decreases with increasing temperature. We use phylogenetically explicit analyses to show that species-mean adult size of aquatic salamanders with branchial or cutaneous oxygen uptake becomes small in warm environments and large in cool environments, whereas body size of aquatic species with lungs (i.e., that respire aerially), as well as size of semiaquatic and terrestrial species do not decrease with temperature. We argue that oxygen limitation drives the evolution of small size in warm aquatic environments for species with aquatic respiration. More broadly, the stronger decline in size with temperature observed in aquatic versus terrestrial salamander species mirrors the relatively strong plastic declines in size observed previously among aquatic versus terrestrial invertebrates, suggesting that temperature-dependent oxygen availability can help drive patterns of plasticity, micro- and macroevolution.}, } @article {pmid29466340, year = {2018}, author = {Shaffer, SM and Dunagin, MC and Torborg, SR and Torre, EA and Emert, B and Krepler, C and Beqiri, M and Sproesser, K and Brafford, PA and Xiao, M and Eggan, E and Anastopoulos, IN and Vargas-Garcia, CA and Singh, A and Nathanson, KL and Herlyn, M and Raj, A}, title = {Corrigendum: Rare cell variability and drug-induced reprogramming as a mode of cancer drug resistance.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {274}, pmid = {29466340}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature22794.}, } @article {pmid29466339, year = {2018}, author = {Macheret, M and Halazonetis, TD}, title = {Intragenic origins due to short G1 phases underlie oncogene-induced DNA replication stress.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {112-116}, pmid = {29466339}, issn = {1476-4687}, support = {294650//European Research Council/International ; }, mesh = {Cell Line, Tumor ; Chromosome Breakpoints ; Cohort Studies ; Cyclin E/genetics/metabolism ; DNA/biosynthesis/genetics ; DNA Breaks, Double-Stranded ; *DNA Replication/genetics ; Female ; G1 Phase/*genetics ; Gene Expression Regulation, Neoplastic ; Genes, myc/genetics ; Genomic Instability/*genetics ; Humans ; Neoplasms/*genetics ; Oncogene Proteins/genetics ; Oncogenes/*genetics ; Replication Origin/*genetics ; S Phase/*genetics ; Transcription, Genetic/genetics ; Translocation, Genetic/genetics ; }, abstract = {Oncogene-induced DNA replication stress contributes critically to the genomic instability that is present in cancer. However, elucidating how oncogenes deregulate DNA replication has been impeded by difficulty in mapping replication initiation sites on the human genome. Here, using a sensitive assay to monitor nascent DNA synthesis in early S phase, we identified thousands of replication initiation sites in cells before and after induction of the oncogenes CCNE1 and MYC. Remarkably, both oncogenes induced firing of a novel set of DNA replication origins that mapped within highly transcribed genes. These ectopic origins were normally suppressed by transcription during G1, but precocious entry into S phase, before all genic regions had been transcribed, allowed firing of origins within genes in cells with activated oncogenes. Forks from oncogene-induced origins were prone to collapse, as a result of conflicts between replication and transcription, and were associated with DNA double-stranded break formation and chromosomal rearrangement breakpoints both in our experimental system and in a large cohort of human cancers. Thus, firing of intragenic origins caused by premature S phase entry represents a mechanism of oncogene-induced DNA replication stress that is relevant for genomic instability in human cancer.}, } @article {pmid29466338, year = {2018}, author = {Borgia, A and Borgia, MB and Bugge, K and Kissling, VM and Heidarsson, PO and Fernandes, CB and Sottini, A and Soranno, A and Buholzer, KJ and Nettels, D and Kragelund, BB and Best, RB and Schuler, B}, title = {Extreme disorder in an ultrahigh-affinity protein complex.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {61-66}, pmid = {29466338}, issn = {1476-4687}, support = {Z99 DK999999/NULL/Intramural NIH HHS/United States ; }, mesh = {Binding Sites ; Histones/*chemistry/*metabolism ; Humans ; Intrinsically Disordered Proteins/*chemistry/*metabolism ; Protein Binding ; Protein Precursors/*chemistry/*metabolism ; Static Electricity ; Thymosin/*analogs & derivatives/chemistry/metabolism ; }, abstract = {Molecular communication in biology is mediated by protein interactions. According to the current paradigm, the specificity and affinity required for these interactions are encoded in the precise complementarity of binding interfaces. Even proteins that are disordered under physiological conditions or that contain large unstructured regions commonly interact with well-structured binding sites on other biomolecules. Here we demonstrate the existence of an unexpected interaction mechanism: the two intrinsically disordered human proteins histone H1 and its nuclear chaperone prothymosin-α associate in a complex with picomolar affinity, but fully retain their structural disorder, long-range flexibility and highly dynamic character. On the basis of closely integrated experiments and molecular simulations, we show that the interaction can be explained by the large opposite net charge of the two proteins, without requiring defined binding sites or interactions between specific individual residues. Proteome-wide sequence analysis suggests that this interaction mechanism may be abundant in eukaryotes.}, } @article {pmid29466337, year = {2018}, author = {Olalde, I and Brace, S and Allentoft, ME and Armit, I and Kristiansen, K and Booth, T and Rohland, N and Mallick, S and Szécsényi-Nagy, A and Mittnik, A and Altena, E and Lipson, M and Lazaridis, I and Harper, TK and Patterson, N and Broomandkhoshbacht, N and Diekmann, Y and Faltyskova, Z and Fernandes, D and Ferry, M and Harney, E and de Knijff, P and Michel, M and Oppenheimer, J and Stewardson, K and Barclay, A and Alt, KW and Liesau, C and Ríos, P and Blasco, C and Miguel, JV and García, RM and Fernández, AA and Bánffy, E and Bernabò-Brea, M and Billoin, D and Bonsall, C and Bonsall, L and Allen, T and Büster, L and Carver, S and Navarro, LC and Craig, OE and Cook, GT and Cunliffe, B and Denaire, A and Dinwiddy, KE and Dodwell, N and Ernée, M and Evans, C and Kuchařík, M and Farré, JF and Fowler, C and Gazenbeek, M and Pena, RG and Haber-Uriarte, M and Haduch, E and Hey, G and Jowett, N and Knowles, T and Massy, K and Pfrengle, S and Lefranc, P and Lemercier, O and Lefebvre, A and Martínez, CH and Olmo, VG and Ramírez, AB and Maurandi, JL and Majó, T and McKinley, JI and McSweeney, K and Mende, BG and Modi, A and Kulcsár, G and Kiss, V and Czene, A and Patay, R and Endrődi, A and Köhler, K and Hajdu, T and Szeniczey, T and Dani, J and Bernert, Z and Hoole, M and Cheronet, O and Keating, D and Velemínský, P and Dobeš, M and Candilio, F and Brown, F and Fernández, RF and Herrero-Corral, AM and Tusa, S and Carnieri, E and Lentini, L and Valenti, A and Zanini, A and Waddington, C and Delibes, G and Guerra-Doce, E and Neil, B and Brittain, M and Luke, M and Mortimer, R and Desideri, J and Besse, M and Brücken, G and Furmanek, M and Hałuszko, A and Mackiewicz, M and Rapiński, A and Leach, S and Soriano, I and Lillios, KT and Cardoso, JL and Pearson, MP and Włodarczak, P and Price, TD and Prieto, P and Rey, PJ and Risch, R and Rojo Guerra, MA and Schmitt, A and Serralongue, J and Silva, AM and Smrčka, V and Vergnaud, L and Zilhão, J and Caramelli, D and Higham, T and Thomas, MG and Kennett, DJ and Fokkens, H and Heyd, V and Sheridan, A and Sjögren, KG and Stockhammer, PW and Krause, J and Pinhasi, R and Haak, W and Barnes, I and Lalueza-Fox, C and Reich, D}, title = {The Beaker phenomenon and the genomic transformation of northwest Europe.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {190-196}, pmid = {29466337}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; R01 GM100233/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromosomes, Human, Y/genetics ; Cultural Evolution/*history ; DNA, Ancient ; Europe ; Gene Pool ; Genetics, Population ; Genome, Human/*genetics ; *Genomics ; Haplotypes ; History, Ancient ; Human Migration/*history ; Humans ; Male ; Spatio-Temporal Analysis ; }, abstract = {From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain's gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries.}, } @article {pmid29466336, year = {2018}, author = {Tusi, BK and Wolock, SL and Weinreb, C and Hwang, Y and Hidalgo, D and Zilionis, R and Waisman, A and Huh, JR and Klein, AM and Socolovsky, M}, title = {Population snapshots predict early haematopoietic and erythroid hierarchies.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {54-60}, pmid = {29466336}, issn = {1476-4687}, support = {R01 DK099281/DK/NIDDK NIH HHS/United States ; R01 DK100915/DK/NIDDK NIH HHS/United States ; T32 GM080177/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Basophils/cytology ; Cell Cycle/genetics/physiology ; Cell Lineage/drug effects/genetics ; Erythrocytes/*cytology/drug effects/metabolism ; Erythroid Precursor Cells/*cytology/drug effects/metabolism ; *Erythropoiesis/drug effects ; Female ; Flow Cytometry ; Intercellular Signaling Peptides and Proteins/genetics/metabolism/pharmacology ; Mast Cells/cytology ; Mice ; Proto-Oncogene Proteins c-kit/metabolism ; RNA, Small Cytoplasmic/analysis/genetics ; Single-Cell Analysis ; Transcriptome ; }, abstract = {The formation of red blood cells begins with the differentiation of multipotent haematopoietic progenitors. Reconstructing the steps of this differentiation represents a general challenge in stem-cell biology. Here we used single-cell transcriptomics, fate assays and a theory that allows the prediction of cell fates from population snapshots to demonstrate that mouse haematopoietic progenitors differentiate through a continuous, hierarchical structure into seven blood lineages. We uncovered coupling between the erythroid and the basophil or mast cell fates, a global haematopoietic response to erythroid stress and novel growth factor receptors that regulate erythropoiesis. We defined a flow cytometry sorting strategy to purify early stages of erythroid differentiation, completely isolating classically defined burst-forming and colony-forming progenitors. We also found that the cell cycle is progressively remodelled during erythroid development and during a sharp transcriptional switch that ends the colony-forming progenitor stage and activates terminal differentiation. Our work showcases the utility of linking transcriptomic data to predictive fate models, and provides insights into lineage development in vivo.}, } @article {pmid29466335, year = {2018}, author = {Quintero, I and Jetz, W}, title = {Global elevational diversity and diversification of birds.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {246-250}, pmid = {29466335}, issn = {1476-4687}, mesh = {*Altitude ; Animals ; *Biodiversity ; Birds/*classification/genetics ; *Geographic Mapping ; Species Specificity ; }, abstract = {Mountain ranges harbour exceptionally high biodiversity, which is now under threat from rapid environmental change. However, despite decades of effort, the limited availability of data and analytical tools has prevented a robust and truly global characterization of elevational biodiversity gradients and their evolutionary origins. This has hampered a general understanding of the processes involved in the assembly and maintenance of montane communities. Here we show that a worldwide mid-elevation peak in bird richness is driven by wide-ranging species and disappears when we use a subsampling procedure that ensures even species representation in space and facilitates evolutionary interpretation. Instead, richness corrected for range size declines linearly with increasing elevation. We find that the more depauperate assemblages at higher elevations are characterized by higher rates of diversification across all mountain regions, rejecting the idea that lower recent diversification rates are the general cause of less diverse biota. Across all elevations, assemblages on mountains with high rates of past temperature change exhibit more rapid diversification, highlighting the importance of climatic fluctuations in driving the evolutionary dynamics of mountain biodiversity. While different geomorphological and climatic attributes of mountain regions have been pivotal in determining the remarkable richness gradients observed today, our results underscore the role of ongoing and often very recent diversification processes in maintaining the unique and highly adapted biodiversity of higher elevations.}, } @article {pmid29466334, year = {2018}, author = {Wang, S and Xu, J and Wang, W and Wang, GN and Rastak, R and Molina-Lopez, F and Chung, JW and Niu, S and Feig, VR and Lopez, J and Lei, T and Kwon, SK and Kim, Y and Foudeh, AM and Ehrlich, A and Gasperini, A and Yun, Y and Murmann, B and Tok, JB and Bao, Z}, title = {Skin electronics from scalable fabrication of an intrinsically stretchable transistor array.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {83-88}, pmid = {29466334}, issn = {1476-4687}, mesh = {Electronics/*instrumentation ; Humans ; *Pliability ; Polymers/chemistry ; Silicon/chemistry ; *Skin ; *Transistors, Electronic ; *Wearable Electronic Devices ; }, abstract = {Skin-like electronics that can adhere seamlessly to human skin or within the body are highly desirable for applications such as health monitoring, medical treatment, medical implants and biological studies, and for technologies that include human-machine interfaces, soft robotics and augmented reality. Rendering such electronics soft and stretchable-like human skin-would make them more comfortable to wear, and, through increased contact area, would greatly enhance the fidelity of signals acquired from the skin. Structural engineering of rigid inorganic and organic devices has enabled circuit-level stretchability, but this requires sophisticated fabrication techniques and usually suffers from reduced densities of devices within an array. We reasoned that the desired parameters, such as higher mechanical deformability and robustness, improved skin compatibility and higher device density, could be provided by using intrinsically stretchable polymer materials instead. However, the production of intrinsically stretchable materials and devices is still largely in its infancy: such materials have been reported, but functional, intrinsically stretchable electronics have yet to be demonstrated owing to the lack of a scalable fabrication technology. Here we describe a fabrication process that enables high yield and uniformity from a variety of intrinsically stretchable electronic polymers. We demonstrate an intrinsically stretchable polymer transistor array with an unprecedented device density of 347 transistors per square centimetre. The transistors have an average charge-carrier mobility comparable to that of amorphous silicon, varying only slightly (within one order of magnitude) when subjected to 100 per cent strain for 1,000 cycles, without current-voltage hysteresis. Our transistor arrays thus constitute intrinsically stretchable skin electronics, and include an active matrix for sensory arrays, as well as analogue and digital circuit elements. Our process offers a general platform for incorporating other intrinsically stretchable polymer materials, enabling the fabrication of next-generation stretchable skin electronic devices.}, } @article {pmid29466333, year = {2018}, author = {Guo, Q and Bin Huang, and Cheng, J and Seefelder, M and Engler, T and Pfeifer, G and Oeckl, P and Otto, M and Moser, F and Maurer, M and Pautsch, A and Baumeister, W and Fernández-Busnadiego, R and Kochanek, S}, title = {The cryo-electron microscopy structure of huntingtin.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {117-120}, pmid = {29466333}, issn = {1476-4687}, support = {318987//European Research Council/International ; }, mesh = {Cryoelectron Microscopy ; Humans ; Huntingtin Protein/chemistry/metabolism/*ultrastructure ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; Nuclear Proteins/chemistry/metabolism/ultrastructure ; Protein Binding ; Protein Domains ; Protein Structure, Secondary ; Static Electricity ; }, abstract = {Huntingtin (HTT) is a large (348 kDa) protein that is essential for embryonic development and is involved in diverse cellular activities such as vesicular transport, endocytosis, autophagy and the regulation of transcription. Although an integrative understanding of the biological functions of HTT is lacking, the large number of identified HTT interactors suggests that it serves as a protein-protein interaction hub. Furthermore, Huntington's disease is caused by a mutation in the HTT gene, resulting in a pathogenic expansion of a polyglutamine repeat at the amino terminus of HTT. However, only limited structural information regarding HTT is currently available. Here we use cryo-electron microscopy to determine the structure of full-length human HTT in a complex with HTT-associated protein 40 (HAP40; encoded by three F8A genes in humans) to an overall resolution of 4 Å. HTT is largely α-helical and consists of three major domains. The amino- and carboxy-terminal domains contain multiple HEAT (huntingtin, elongation factor 3, protein phosphatase 2A and lipid kinase TOR) repeats arranged in a solenoid fashion. These domains are connected by a smaller bridge domain containing different types of tandem repeats. HAP40 is also largely α-helical and has a tetratricopeptide repeat-like organization. HAP40 binds in a cleft and contacts the three HTT domains by hydrophobic and electrostatic interactions, thereby stabilizing the conformation of HTT. These data rationalize previous biochemical results and pave the way for improved understanding of the diverse cellular functions of HTT.}, } @article {pmid29466332, year = {2018}, author = {Liang, YL and Khoshouei, M and Glukhova, A and Furness, SGB and Zhao, P and Clydesdale, L and Koole, C and Truong, TT and Thal, DM and Lei, S and Radjainia, M and Danev, R and Baumeister, W and Wang, MW and Miller, LJ and Christopoulos, A and Sexton, PM and Wootten, D}, title = {Phase-plate cryo-EM structure of a biased agonist-bound human GLP-1 receptor-Gs complex.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {121-125}, pmid = {29466332}, issn = {1476-4687}, mesh = {Binding Sites ; *Cryoelectron Microscopy ; GTP-Binding Protein alpha Subunits, Gs/*chemistry/*ultrastructure ; Glucagon-Like Peptide 1/*chemistry/metabolism/*pharmacology ; Glucagon-Like Peptide-1 Receptor/*agonists/chemistry/*ultrastructure ; Humans ; Models, Molecular ; Protein Conformation ; }, abstract = {The class B glucagon-like peptide-1 (GLP-1) G protein-coupled receptor is a major target for the treatment of type 2 diabetes and obesity. Endogenous and mimetic GLP-1 peptides exhibit biased agonism-a difference in functional selectivity-that may provide improved therapeutic outcomes. Here we describe the structure of the human GLP-1 receptor in complex with the G protein-biased peptide exendin-P5 and a Gαs heterotrimer, determined at a global resolution of 3.3 Å. At the extracellular surface, the organization of extracellular loop 3 and proximal transmembrane segments differs between our exendin-P5-bound structure and previous GLP-1-bound GLP-1 receptor structure. At the intracellular face, there was a six-degree difference in the angle of the Gαs-α5 helix engagement between structures, which was propagated across the G protein heterotrimer. In addition, the structures differed in the rate and extent of conformational reorganization of the Gαs protein. Our structure provides insights into the molecular basis of biased agonism.}, } @article {pmid29466331, year = {2018}, author = {Ma, Z and Guo, D and Xu, X and Lu, M and Bardgett, RD and Eissenstat, DM and McCormack, ML and Hedin, LO}, title = {Evolutionary history resolves global organization of root functional traits.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {94-97}, pmid = {29466331}, issn = {1476-4687}, mesh = {Biodiversity ; *Biological Evolution ; Carbon/metabolism ; Databases, Factual ; Desert Climate ; *Ecosystem ; Mycorrhizae/physiology ; Photosynthesis ; Phylogeny ; Plant Roots/*anatomy & histology/classification/microbiology/*physiology ; Seasons ; Soil/chemistry ; Species Specificity ; Symbiosis ; Tropical Climate ; }, abstract = {Plant roots have greatly diversified in form and function since the emergence of the first land plants, but the global organization of functional traits in roots remains poorly understood. Here we analyse a global dataset of 10 functionally important root traits in metabolically active first-order roots, collected from 369 species distributed across the natural plant communities of 7 biomes. Our results identify a high degree of organization of root traits across species and biomes, and reveal a pattern that differs from expectations based on previous studies of leaf traits. Root diameter exerts the strongest influence on root trait variation across plant species, growth forms and biomes. Our analysis suggests that plants have evolved thinner roots since they first emerged in land ecosystems, which has enabled them to markedly improve their efficiency of soil exploration per unit of carbon invested and to reduce their dependence on symbiotic mycorrhizal fungi. We also found that diversity in root morphological traits is greatest in the tropics, where plant diversity is highest and many ancestral phylogenetic groups are preserved. Diversity in root morphology declines sharply across the sequence of tropical, temperate and desert biomes, presumably owing to changes in resource supply caused by seasonally inhospitable abiotic conditions. Our results suggest that root traits have evolved along a spectrum bounded by two contrasting strategies of root life: an ancestral 'conservative' strategy in which plants with thick roots depend on symbiosis with mycorrhizal fungi for soil resources and a more-derived 'opportunistic' strategy in which thin roots enable plants to more efficiently leverage photosynthetic carbon for soil exploration. These findings imply that innovations of belowground traits have had an important role in preparing plants to colonize new habitats, and in generating biodiversity within and across biomes.}, } @article {pmid29466330, year = {2018}, author = {Mathieson, I and Alpaslan-Roodenberg, S and Posth, C and Szécsényi-Nagy, A and Rohland, N and Mallick, S and Olalde, I and Broomandkhoshbacht, N and Candilio, F and Cheronet, O and Fernandes, D and Ferry, M and Gamarra, B and Fortes, GG and Haak, W and Harney, E and Jones, E and Keating, D and Krause-Kyora, B and Kucukkalipci, I and Michel, M and Mittnik, A and Nägele, K and Novak, M and Oppenheimer, J and Patterson, N and Pfrengle, S and Sirak, K and Stewardson, K and Vai, S and Alexandrov, S and Alt, KW and Andreescu, R and Antonović, D and Ash, A and Atanassova, N and Bacvarov, K and Gusztáv, MB and Bocherens, H and Bolus, M and Boroneanţ, A and Boyadzhiev, Y and Budnik, A and Burmaz, J and Chohadzhiev, S and Conard, NJ and Cottiaux, R and Čuka, M and Cupillard, C and Drucker, DG and Elenski, N and Francken, M and Galabova, B and Ganetsovski, G and Gély, B and Hajdu, T and Handzhyiska, V and Harvati, K and Higham, T and Iliev, S and Janković, I and Karavanić, I and Kennett, DJ and Komšo, D and Kozak, A and Labuda, D and Lari, M and Lazar, C and Leppek, M and Leshtakov, K and Vetro, DL and Los, D and Lozanov, I and Malina, M and Martini, F and McSweeney, K and Meller, H and Menđušić, M and Mirea, P and Moiseyev, V and Petrova, V and Price, TD and Simalcsik, A and Sineo, L and Šlaus, M and Slavchev, V and Stanev, P and Starović, A and Szeniczey, T and Talamo, S and Teschler-Nicola, M and Thevenet, C and Valchev, I and Valentin, F and Vasilyev, S and Veljanovska, F and Venelinova, S and Veselovskaya, E and Viola, B and Virag, C and Zaninović, J and Zäuner, S and Stockhammer, PW and Catalano, G and Krauß, R and Caramelli, D and Zariņa, G and Gaydarska, B and Lillie, M and Nikitin, AG and Potekhina, I and Papathanasiou, A and Borić, D and Bonsall, C and Krause, J and Pinhasi, R and Reich, D}, title = {The genomic history of southeastern Europe.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {197-203}, pmid = {29466330}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; 263441//European Research Council/International ; R01 GM100233/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Agriculture/history ; Asia/ethnology ; DNA, Ancient ; Europe ; Farmers/*history ; Female ; Genetics, Population ; Genome, Human/*genetics ; *Genomics ; Grassland ; History, Ancient ; Human Migration/*history ; Humans ; Male ; Sex Distribution ; }, abstract = {Farming was first introduced to Europe in the mid-seventh millennium bc, and was associated with migrants from Anatolia who settled in the southeast before spreading throughout Europe. Here, to understand the dynamics of this process, we analysed genome-wide ancient DNA data from 225 individuals who lived in southeastern Europe and surrounding regions between 12000 and 500 bc. We document a west-east cline of ancestry in indigenous hunter-gatherers and, in eastern Europe, the early stages in the formation of Bronze Age steppe ancestry. We show that the first farmers of northern and western Europe dispersed through southeastern Europe with limited hunter-gatherer admixture, but that some early groups in the southeast mixed extensively with hunter-gatherers without the sex-biased admixture that prevailed later in the north and west. We also show that southeastern Europe continued to be a nexus between east and west after the arrival of farmers, with intermittent genetic contact with steppe populations occurring up to 2,000 years earlier than the migrations from the steppe that ultimately replaced much of the population of northern Europe.}, } @article {pmid29466329, year = {2018}, author = {Yadlapalli, S and Jiang, C and Bahle, A and Reddy, P and Meyhofer, E and Shafer, OT}, title = {Circadian clock neurons constantly monitor environmental temperature to set sleep timing.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {98-102}, pmid = {29466329}, issn = {1476-4687}, support = {R01 NS077933/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Circadian Clocks/*physiology ; Circadian Rhythm/*physiology ; Cold Temperature ; Drosophila melanogaster/anatomy & histology/cytology/*physiology ; Female ; Hot Temperature ; Locomotion/physiology ; Male ; Nerve Net/cytology/physiology ; Neural Inhibition ; Neurons/*physiology ; Sleep/*physiology ; *Temperature ; Thermoreceptors/metabolism ; Thermosensing/*physiology ; Time Factors ; }, abstract = {Circadian clocks coordinate behaviour, physiology and metabolism with Earth's diurnal cycle. These clocks entrain to both light and temperature cycles, and daily environmental temperature oscillations probably contribute to human sleep patterns. However, the neural mechanisms through which circadian clocks monitor environmental temperature and modulate behaviour remain poorly understood. Here we elucidate how the circadian clock neuron network of Drosophila melanogaster processes changes in environmental temperature. In vivo calcium-imaging techniques demonstrate that the posterior dorsal neurons 1 (DN1ps), which are a discrete subset of sleep-promoting clock neurons, constantly monitor modest changes in environmental temperature. We find that these neurons are acutely inhibited by heating and excited by cooling; this is an unexpected result when considering the strong correlation between temperature and light, and the fact that light excites clock neurons. We demonstrate that the DN1ps rely on peripheral thermoreceptors located in the chordotonal organs and the aristae. We also show that the DN1ps and their thermosensory inputs are required for the normal timing of sleep in the presence of naturalistic temperature cycles. These results identify the DN1ps as a major gateway for temperature sensation into the circadian neural network, which continuously integrates temperature changes to coordinate the timing of sleep and activity.}, } @article {pmid29466328, year = {2018}, author = {von Hoegen, A and Mankowsky, R and Fechner, M and Först, M and Cavalleri, A}, title = {Probing the interatomic potential of solids with strong-field nonlinear phononics.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {79-82}, pmid = {29466328}, issn = {1476-4687}, abstract = {Nonlinear optical techniques at visible frequencies have long been applied to condensed matter spectroscopy. However, because many important excitations of solids are found at low energies, much can be gained from the extension of nonlinear optics to mid-infrared and terahertz frequencies. For example, the nonlinear excitation of lattice vibrations has enabled the dynamic control of material functions. So far it has only been possible to exploit second-order phonon nonlinearities at terahertz field strengths near one million volts per centimetre. Here we achieve an order-of-magnitude increase in field strength and explore higher-order phonon nonlinearities. We excite up to five harmonics of the A1 (transverse optical) phonon mode in the ferroelectric material lithium niobate. By using ultrashort mid-infrared laser pulses to drive the atoms far from their equilibrium positions, and measuring the large-amplitude atomic trajectories, we can sample the interatomic potential of lithium niobate, providing a benchmark for ab initio calculations for the material. Tomography of the energy surface by high-order nonlinear phononics could benefit many aspects of materials research, including the study of classical and quantum phase transitions.}, } @article {pmid29466327, year = {2018}, author = {Bai, L and Wang, T and Zhao, G and Kovach, A and Li, H}, title = {The atomic structure of a eukaryotic oligosaccharyltransferase complex.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {328-333}, pmid = {29466327}, issn = {1476-4687}, support = {R01 GM111742/GM/NIGMS NIH HHS/United States ; }, mesh = {Allosteric Regulation ; Biocatalysis ; Catalytic Domain ; *Cryoelectron Microscopy ; Glycosylation ; Hexosyltransferases/*chemistry/metabolism/*ultrastructure ; Membrane Proteins/*chemistry/metabolism/*ultrastructure ; Models, Molecular ; Phospholipids/metabolism ; Protein Subunits/chemistry ; Saccharomyces cerevisiae/*enzymology ; Saccharomyces cerevisiae Proteins/*chemistry/*ultrastructure ; }, abstract = {N-glycosylation is a ubiquitous modification of eukaryotic secretory and membrane-bound proteins; about 90% of glycoproteins are N-glycosylated. The reaction is catalysed by an eight-protein oligosaccharyltransferase (OST) complex that is embedded in the endoplasmic reticulum membrane. Our understanding of eukaryotic protein N-glycosylation has been limited owing to the lack of high-resolution structures. Here we report a 3.5 Å resolution cryo-electron microscopy structure of the Saccharomyces cerevisiae OST complex, revealing the structures of subunits Ost1-Ost5, Stt3, Wbp1 and Swp1. We found that seven phospholipids mediate many of the inter-subunit interactions, and an Stt3 N-glycan mediates interactions with Wbp1 and Swp1 in the lumen. Ost3 was found to mediate the OST-Sec61 translocon interface, funnelling the acceptor peptide towards the OST catalytic site as the nascent peptide emerges from the translocon. The structure provides insights into co-translational protein N-glycosylation, and may facilitate the development of small-molecule inhibitors that target this process.}, } @article {pmid29466326, year = {2018}, author = {Wang, S and Che, T and Levit, A and Shoichet, BK and Wacker, D and Roth, BL}, title = {Structure of the D2 dopamine receptor bound to the atypical antipsychotic drug risperidone.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {269-273}, pmid = {29466326}, issn = {1476-4687}, support = {U19 MH082441/MH/NIMH NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 MH112205/MH/NIMH NIH HHS/United States ; R35 GM122481/GM/NIGMS NIH HHS/United States ; R01 MH061887/MH/NIMH NIH HHS/United States ; R01 GM059957/GM/NIGMS NIH HHS/United States ; }, mesh = {Antipsychotic Agents/*chemistry/*metabolism ; Binding Sites ; Crystallography, X-Ray ; Drug Design ; Humans ; Hydrophobic and Hydrophilic Interactions ; Kinetics ; Ligands ; Models, Molecular ; Mutant Proteins/chemistry/genetics/metabolism ; Mutation ; Receptors, Dopamine D2/*chemistry/genetics/*metabolism ; Receptors, Dopamine D3/chemistry/metabolism ; Receptors, Dopamine D4/chemistry/metabolism ; Risperidone/*chemistry/*metabolism ; }, abstract = {Dopamine is a neurotransmitter that has been implicated in processes as diverse as reward, addiction, control of coordinated movement, metabolism and hormonal secretion. Correspondingly, dysregulation of the dopaminergic system has been implicated in diseases such as schizophrenia, Parkinson's disease, depression, attention deficit hyperactivity disorder, and nausea and vomiting. The actions of dopamine are mediated by a family of five G-protein-coupled receptors. The D2 dopamine receptor (DRD2) is the primary target for both typical and atypical antipsychotic drugs, and for drugs used to treat Parkinson's disease. Unfortunately, many drugs that target DRD2 cause serious and potentially life-threatening side effects due to promiscuous activities against related receptors. Accordingly, a molecular understanding of the structure and function of DRD2 could provide a template for the design of safer and more effective medications. Here we report the crystal structure of DRD2 in complex with the widely prescribed atypical antipsychotic drug risperidone. The DRD2-risperidone structure reveals an unexpected mode of antipsychotic drug binding to dopamine receptors, and highlights structural determinants that are essential for the actions of risperidone and related drugs at DRD2.}, } @article {pmid29466325, year = {2018}, author = {Christoph, J and Chebbok, M and Richter, C and Schröder-Schetelig, J and Bittihn, P and Stein, S and Uzelac, I and Fenton, FH and Hasenfuß, G and Gilmour, RF and Luther, S}, title = {Electromechanical vortex filaments during cardiac fibrillation.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {667-672}, pmid = {29466325}, issn = {1476-4687}, mesh = {Animals ; Arrhythmias, Cardiac/*diagnostic imaging/pathology/*physiopathology ; Calcium/metabolism ; Computer Simulation ; Female ; Heart Ventricles/*diagnostic imaging/*physiopathology ; Membrane Potentials ; Models, Biological ; *Myocardial Contraction ; Rabbits ; Swine ; Swine, Miniature ; Ultrasonography ; }, abstract = {The self-organized dynamics of vortex-like rotating waves, which are also known as scroll waves, are the basis of the formation of complex spatiotemporal patterns in many excitable chemical and biological systems. In the heart, filament-like phase singularities that are associated with three-dimensional scroll waves are considered to be the organizing centres of life-threatening cardiac arrhythmias. The mechanisms that underlie the onset, maintenance and control of electromechanical turbulence in the heart are inherently three-dimensional phenomena. However, it has not previously been possible to visualize the three-dimensional spatiotemporal dynamics of scroll waves inside cardiac tissues. Here we show that three-dimensional mechanical scroll waves and filament-like phase singularities can be observed deep inside the contracting heart wall using high-resolution four-dimensional ultrasound-based strain imaging. We found that mechanical phase singularities co-exist with electrical phase singularities during cardiac fibrillation. We investigated the dynamics of electrical and mechanical phase singularities by simultaneously measuring the membrane potential, intracellular calcium concentration and mechanical contractions of the heart. We show that cardiac fibrillation can be characterized using the three-dimensional spatiotemporal dynamics of mechanical phase singularities, which arise inside the fibrillating contracting ventricular wall. We demonstrate that electrical and mechanical phase singularities show complex interactions and we characterize their dynamics in terms of trajectories, topological charge and lifetime. We anticipate that our findings will provide novel perspectives for non-invasive diagnostic imaging and therapeutic applications.}, } @article {pmid29466324, year = {2018}, author = {Lubelsky, Y and Ulitsky, I}, title = {Sequences enriched in Alu repeats drive nuclear localization of long RNAs in human cells.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {107-111}, pmid = {29466324}, issn = {1476-4687}, support = {637878//European Research Council/International ; }, mesh = {Active Transport, Cell Nucleus ; Alu Elements/*genetics ; Animals ; Base Sequence ; Binding Sites ; Cell Nucleus/*genetics ; Conserved Sequence ; Evolution, Molecular ; HeLa Cells ; Heterogeneous-Nuclear Ribonucleoprotein K/metabolism ; Humans ; MCF-7 Cells ; Mice ; *RNA Transport ; RNA, Long Noncoding/*genetics/*metabolism ; RNA, Messenger/*genetics/*metabolism ; Species Specificity ; Untranslated Regions/genetics ; }, abstract = {Long noncoding RNAs (lncRNAs) are emerging as key parts of multiple cellular pathways, but their modes of action and how these are dictated by sequence remain unclear. lncRNAs tend to be enriched in the nuclear fraction, whereas most mRNAs are overtly cytoplasmic, although several studies have found that hundreds of mRNAs in various cell types are retained in the nucleus. It is thus conceivable that some mechanisms that promote nuclear enrichment are shared between lncRNAs and mRNAs. Here, to identify elements in lncRNAs and mRNAs that can force nuclear localization, we screened libraries of short fragments tiled across nuclear RNAs, which were cloned into the untranslated regions of an efficiently exported mRNA. The screen identified a short sequence derived from Alu elements and bound by HNRNPK that increased nuclear accumulation. Binding of HNRNPK to C-rich motifs outside Alu elements is also associated with nuclear enrichment in both lncRNAs and mRNAs, and this mechanism is conserved across species. Our results thus identify a pathway for regulation of RNA accumulation and subcellular localization that has been co-opted to regulate the fate of transcripts with integrated Alu elements.}, } @article {pmid29465798, year = {2018}, author = {Gomez-Llano, MA and Bensch, HM and Svensson, EI}, title = {Sexual conflict and ecology: Species composition and male density interact to reduce male mating harassment and increase female survival.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {906-915}, doi = {10.1111/evo.13457}, pmid = {29465798}, issn = {1558-5646}, abstract = {Sexual conflict is a pervasive evolutionary force that can reduce female fitness. Experimental evolution studies in the laboratory might overestimate the importance of sexual conflict because the ecological conditions in such settings typically include only a single species. Here, we experimentally manipulated conspecific male density (high or low) and species composition (sympatric or allopatric) to investigate how ecological conditions affect female survival in a sexually dimorphic insect, the banded demoiselle (Calopteryx splendens). Female survival was strongly influenced by an interaction between male density and species composition. Specifically, at low conspecific male density, female survival increased in the presence of heterospecific males (C. virgo). Behavioral mating experiments showed that interspecific interference competition reduced conspecific male mating success with large females. These findings suggest that reproductive interference competition between con- and heterospecific males might indirectly facilitate female survival by reducing mating harassment from conspecific males. Hence, interspecific competitors can show contrasting effects on the two sexes thereby influencing sexual conflict dynamics. Our results call for incorporation of more ecological realism in sexual conflict research, particularly how local community context and reproductive interference competition between heterospecific males can affect female fitness.}, } @article {pmid29465343, year = {2018}, author = {Liu, MJ and Jin, CZ and Park, DJ and Asem, MD and Xiao, M and Salam, N and Li, WJ and Kim, CJ}, title = {Stackebrandtia soli sp. nov., a novel actinobacterium isolated from a soil sample.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1215-1219}, doi = {10.1099/ijsem.0.002654}, pmid = {29465343}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/chemistry ; }, abstract = {An aerobic actinobacterium, strain AN130378T, was isolated from a soil sample collected in Korea and subjected to taxonomic investigation using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence data showed that strain AN130378T is a member of the genus Stackebrandtia, with sequence similarities of 97.3 % to Stackebrandtia albiflava YIM 45751T and 97.1 % to Stackebrandtia endophytica YIM 64602T. The whole-cell hydrolysates contained meso-diaminopimelic acid as the diagnostic diamino acid, and galactose, glucose and xylose. The major menaquinones were MK-11(H4), MK-10(H4) and MK-11(H6), while the major fatty acids were identified as iso-C15 : 0, anteiso-C17 : 0, anteiso-C15 : 0, iso-C17 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c). The polar lipids were identified as diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylmethylethanolamine, an unidentified aminophospholipid, four unidentified glycolipids, three unidentified phospholipids and two unidentified polar lipids. The G+C content of the genomic DNA was determined to be 67.7 mol%. All chemotaxonomic and genotypic data indicated that the strain belongs to the genus Stackebrandtia. On the basis of morphological, chemotaxonomic data and phylogenetic analysis, strain AN130378T is considered to represent a novel species within the genus Stackebrandtia, for which the name Stackebrandtia soli sp. nov. is proposed. The type strain is AN130378T (=DSM 103573T=KCTC 39809T).}, } @article {pmid29465340, year = {2018}, author = {Liu, Y and Yu, M and Zhang, XH}, title = {Bacillus alkalitolerans sp. nov., isolated from marine sediment near a hydrothermal vent.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1184-1189}, doi = {10.1099/ijsem.0.002648}, pmid = {29465340}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Hydrothermal Vents/*microbiology ; Nucleic Acid Hybridization ; Pacific Ocean ; Peptidoglycan/chemistry ; Phosphatidylglycerols/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, endospore-forming, rod-shaped, motile and strictly aerobic strain, designated T3-209T, was isolated from sediment sampled at a water depth of 1206 m of the southern Okinawa Trough at station T1 (25.07° N, 122.58° E) near the Tangyin hydrothermal vent during an expedition on the R/V Kexue in May 2014. The strain was able to grow at a temperature range of 10-42 °C (optimum 28 °C). Growth was observed at NaCl concentrations (w/v) of 0-6 % (optimum 0 %). The pH range for growth was 7.0-9.0 (optimum 8.0). The 16S rRNA gene sequence analysis indicated that strain T3-209T belonged to the genus Bacillus within the family Bacillaceae and was most closely related to Bacillus drentensis LMG 21831T and Bacillus bataviensis LMG 21833T, with the same sequence similarity (97.0 %), but shared relatively low levels of similarity (92.6-96.9 %) to the type strains of other Bacillus species. The peptidoglycan type of strain T3-209T was meso-diaminopimelic acid. The predominant cellular fatty acids were anteiso-C15 : 0, iso-C15 : 0 and alcohol-C16 : 1ω7c. The respiratory quinone was menaquinone-7. The polar lipids of strain T3-209T comprised phosphatidylglycerol, two unidentified phospholipids and one unidentified aminolipid. The DNA G+C content was 41.8 mol%. Combining results of phylogenetic analysis, phenotypic characterization and chemotaxonomic studies, strain T3-209T represents a novel species of the genus Bacillus, for which the name Bacillus alkalitolerans sp. nov. is proposed. The type strain is T3-209T (=KCTC 33631T=DSM 29135T=MCCC 1K00503T).}, } @article {pmid29465339, year = {2018}, author = {Belova, SE and Suzina, NE and Rijpstra, WIC and Sinninghe Damsté, JS and Dedysh, SN}, title = {Edaphobacter lichenicola sp. nov., a member of the family Acidobacteriaceae from lichen-dominated forested tundra.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002663}, pmid = {29465339}, issn = {1466-5034}, abstract = {An isolate of aerobic, Gram-stain-negative, rod-shaped, non-motile and light-pink pigmented bacteria, designated SBC68T, was obtained from slightly decomposed thalli of the lichen Cladonia sp. collected from the forested tundra of north-western Siberia. Cells of this isolate occurred singly, in pairs or in rosettes. These bacteria were acidophilic (optimum growth at pH 4.3-5.6) and mesophilic (optimum growth at 20-30 °C) but were also capable of growth at low temperatures, down to 7 °C. The preferred growth substrates were sugars, some organic acids and lichenan. The major fatty acids were iso-C15 : 0, C16 : 1ω7c, C16 : 0, C16 : 1ω7t, and 13,16-dimethyl octacosanedioic acid. The only quinone was MK-8, and the G+C content of the DNA was 54.7 mol%. SBC68T represented a member of the family Acidobactericeae; the closest taxonomically described relatives were Edaphobacter dinghuensis DHF9T and Granulicella aggregans TPB6028T (97.2 and 97.1 % 16S rRNA gene sequence similarity, respectively). In 16S rRNA gene-based trees, SBC68T clustered together with species of the genus Edaphobacter. However, this isolate differed from all previously described species of the genus Edaphobacter with respect to the pink pigmentation, formation of cell rosettes and substrate utilization pattern. On the basis of these data, strain SBC68T should be considered to represent a novel species of acidobacteria, for which the name Edaphobacterlichenicola sp. nov. is proposed. The type strain is SBC68T (=DSM 104462T=VKM B-3208T).}, } @article {pmid29465338, year = {2018}, author = {Tak, EJ and Kim, HS and Lee, JY and Kang, W and Sung, H and Kim, PS and Hyun, DW and Shin, NR and Roh, JR and Park, SD and Shim, HE and Bae, JW}, title = {Virgibacillus phasianinus sp. nov., a halophilic bacterium isolated from faeces of a Swinhoe's pheasant, Lophura swinhoii.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1190-1196}, doi = {10.1099/ijsem.0.002650}, pmid = {29465338}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry ; Feces/*microbiology ; Galliformes/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Virgibacillus/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A rod-shaped, Gram-stain-positive, motile and aerobic bacterium, designated LM2416T, was isolated from faeces of Lophuras winhoii living in Seoul Grand Park, Gyeonggi-do, Republic of Korea. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain LM2416T belonged to the genus Virgibacillus, sharing high 16S rRNA gene sequence similarities to Virgibacillus necropolis LMG 19488T (99.0 %), Virgibacillus carmonensis LMG 20964T (98.4 %), Virgibacillus arcticus Hal 1T (98.3 %) and Virgibacillus flavescens S1-20T (97.9 %). The isolate grew at 10-30 °C, pH 6-7 and 0-20 % (w/v) NaCl. Optimal growth was observed at 30 °C, pH 6-7 and 10 % (w/v) NaCl. The major fatty acid was anteiso-C15 : 0. Polar lipids were composed of phosphatidylglycerol, diphosphatidylglycerol, three unknown phospholipids and two unknown aminophospholipids. The main menaquinone was MK-7. Strain LM2416T had alanine, lysine, glutamic acid, glycine and aspartic acid as cell-wall amino acids and ribose as a cell-wall sugar. The whole genome sequences of strain LM2416T and V. necropolis KCTC 3820T were sequenced by PacBio RS II sequencing. The genome sequence-based G+C content of strain LM2416T was 39.5 mol%. The orthologous average nucleotide identity value, showing genetic relatedness between strain LM2416T and V. necropolis KCTC 3820T, was 78.3 %. Based on the phylogenetic, biochemical, chemotaxonomic and genotypic data presented in this study, strain LM2416T is considered to represent a novel species of the genus Virgibacillus, for which the name Virgibacillus phasianinus is proposed. The type strain is LM2416T (=KCTC 33927T=JCM 32144T).}, } @article {pmid29465337, year = {2018}, author = {Lee, KC and Suh, MK and Eom, MK and Kim, KK and Kim, JS and Kim, DS and Ko, SH and Shin, YK and Lee, JS}, title = {Jatrophihabitans telluris sp. nov., isolated from sediment soil of lava forest wetlands and the emended description of the genus Jatrophihabitans.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1107-1111}, doi = {10.1099/ijsem.0.002639}, pmid = {29465337}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Glycolipids/chemistry ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; *Wetlands ; }, abstract = {A novel actinobacterial strain, designated N237T, was isolated from sediment soil of wetlands at Meonmulkkak, Dongbaek-Dongsan, the lava forest, Gotjawal, Jeju, Republic of Korea. Cells of strain N237T were Gram-stain-positive, non-motile rods and formed pale yellow colonies on ten-fold diluted Reasoner's 2A agar. Strain N237T contained iso-C16 : 0 and C17 : 1ω8c as the major fatty acids, MK-9(H4) as the predominant isoprenoid quinone and meso-DAP as the diamino acid in the peptidoglycan. It contained diphosphatidylglycerol, phosphatidylinositol polymannosides, an unidentified phospholipid, an unidentified aminophospholipid, an unidentified aminolipid, two unidentified glycophospholipids, three unidentified glycolipids and two unidentified lipids as polar lipids. The DNA G+C content was 68.1 mol%. Strain N237T formed a separate lineage in the genus Jatrophihabitans, as demonstrated by phylogenetic analysis based on 16S rRNA sequencing. It was most closely related to Jatrophihabitans soli KIS75-12T (95.6 % sequence similarity). The combined phenotypic, chemotaxonomic and phylogenetic characteristics supported the conclusion that strain N237T represents a novel species in the genus Jatrophihabitans, for which the name Jatrophihabitans telluris sp. nov. is proposed. The type strain is N237T (=KCTC 39922T=NRRL B-65477T).}, } @article {pmid29464694, year = {2018}, author = {Weber, MG and Cacho, NI and Phan, MJQ and Disbrow, C and Ramírez, SR and Strauss, SY}, title = {The evolution of floral signals in relation to range overlap in a clade of California Jewelflowers (Streptanthus s.l.).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {798-807}, doi = {10.1111/evo.13456}, pmid = {29464694}, issn = {1558-5646}, abstract = {Because of their function as reproductive signals in plants, floral traits experience distinct selective pressures related to their role in speciation, reinforcement, and prolonged coexistence with close relatives. However, few studies have investigated whether population-level processes translate into detectable signatures at the macroevolutionary scale. Here, we ask whether patterns of floral trait evolution and range overlap across a clade of California Jewelflowers reflect processes hypothesized to shape floral signal differentiation at the population level. We found a pattern of divergence in floral scent composition across the clade such that close relatives had highly disparate floral scents given their age. Accounting for range overlap with close relatives explained additional variation in floral scent over time, with sympatric species pairs having diverged more than allopatric species pairs given their age. However, three other floral traits (flower size, scent complexity and flower color) did not fit these patterns, failing to deviate from a null Brownian motion model of evolution. Together, our results suggest that selection for divergence among close relatives in the composition of floral scents may play a key, sustained role in mediating speciation and coexistence dynamics across this group, and that signatures of these dynamics may persist at the macroevolutionary scale.}, } @article {pmid29464363, year = {2018}, author = {Hettiarachchi, SA and Lee, SJ and Lee, Y and Kwon, YK and Kwon, KK and Yang, SH and Jo, E and Kang, DH and Oh, C}, title = {Corallibacterium pacifica gen. nov., sp. nov., a Novel Bacterium of the Family Vibrionaceae Isolated from Hard Coral.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {835-841}, pmid = {29464363}, issn = {1432-0991}, mesh = {Animals ; Anthozoa/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry/metabolism ; Micronesia ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Vibrionaceae/classification/genetics/*isolation & purification/metabolism ; }, abstract = {A gram-negative, rod-shaped, motile, oxidase- and catalase-positive, non-pigmented marine bacterium, designated strain OS-11M-2T, was isolated from a coral sample collected from the Osakura coastal area in Micronesia. Phylogenetic analysis based on 16S ribosomal RNA (rRNA) gene sequences indicated that strain OS-11M-2T is a member of the family Vibrionaceae, its closest neighbors being Photobacterium damselae subsp. piscicida NCIMB 2058T (94.9%), Photobacterium damselae subsp. damselae CIP 102761T (94.75%), Grimontia marina IMCC5001T (94.5%), Enterovibrio coralii LMG 22228T (94.5%), and Grimontia celer 96-237T (94.5%). The major cellular fatty acids were summed feature 3 (21.4%), summed feature 8 (18.5%), iso-C16:0 (13.8%), and C16:0 (11.9%). The major respiratory quinone of the bacterium was ubiquinone-8 (Q-8) and its major polar lipid phosphatidylethanolamine. Six amino lipids, two phospholipids, and one polar lipid, all unidentified, were detected. The DNA G+C content was 49.7 mol%. The 16S rRNA gene sequence of OS-11M-2T was registered in GenBank under accession number MF359550. On the basis of phenotypic, genotypic, and phylogenetic analyses, strain OS-11M-2T represents a novel genus of the family Vibrionaceae, for which we propose the name Corallibacterium pacifica gen. nov., sp. nov., with the type strain of the type species being OS-11M-2T (= KCCM 43265T). The digital protologue database (DPD) taxon number for strain OS-11M-2T is GA00041.}, } @article {pmid29464362, year = {2018}, author = {Yadav, AK and Sirohi, P and Saraswat, S and Rani, M and Singh, MP and Srivastava, S and Singh, NK}, title = {Inhibitory Mechanism on Combination of Phytic Acid with Methanolic Seed Extract of Syzygium cumini and Sodium Chloride over Bacillus subtilis.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {849-856}, pmid = {29464362}, issn = {1432-0991}, mesh = {Anti-Bacterial Agents/chemistry/isolation & purification/*pharmacology ; Bacillus subtilis/*drug effects/growth & development ; Cell Membrane/drug effects ; Drug Synergism ; Drugs, Chinese Herbal/chemistry/isolation & purification/*pharmacology ; Phytic Acid/*pharmacology ; Pseudomonas aeruginosa/drug effects/growth & development ; Seeds/*chemistry ; Syzygium/*chemistry ; }, abstract = {The antibiotic resistance in bacteria responsible for causing community and health care-associated infection displayed a major threat to global health. Use of broad-spectrum antibiotics for the treatment of various ailments poses serious side effects. In the present research, we investigated the combined role of 2% phytic acid with 2% methanolic seed extract of Syzygium cumini and 0.5% sodium chloride for inhibition of Bacillus subtilis and Pseudomonas aeruginosa and found it to be efficient over B. subtilis. The zone of inhibition by present mixture was found to be 2.9 ± 0.0004 and 1.9 ± 0.0006 cm against Bacillus subtilis and P. aeruginosa in comparison to individual component. Mixture was found more potent against B. subtilis and selected for further study. The underlying mechanism involved in inhibitory action of this mixture was determined by Scanning electron microscope, DNA fragmentation and propidium iodide staining. Scanning electron microscopy revealed that inhibition of B. subtilis by this mixture is mainly due to the disruption of bacterial cell membrane, leakage of internal cellular content which ultimately leads to the death of bacterial cells. DNA fragmentation showed apoptotic hallmark through degradation caused by mixture against B. subtilis at various time intervals. Likewise, PI staining also revealed the disruption of bacterial membrane by the mixture as the PI gives fluorescence after binding with DNA. The present study concludes that inhibitory potential of this mixture is mainly due to disruption of bacterial cell membrane, degradation of DNA and creation of pores in the membrane. The mixture could be used for inhibition of food pathogen B. subtilis.}, } @article {pmid29464361, year = {2018}, author = {Huq, MA and Akter, S and Lee, SY}, title = {Flavobacterium chungangensis sp. nov., a Bacterium Isolated from Soil of Chinese Cabbage Garden.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {842-848}, pmid = {29464361}, issn = {1432-0991}, support = {NRF-2016R1A2B4014591//Cooperative Research Program of the National Research Foundation of Korea grant/ ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; Brassica/*growth & development ; DNA, Bacterial/genetics ; Fatty Acids/chemistry/metabolism ; Flavobacterium/classification/genetics/*isolation & purification/metabolism ; Gardens ; Nucleic Acid Hybridization ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; *Soil Microbiology ; }, abstract = {A novel bacterial strain MAH-10T was isolated from soil sample of a Chinese cabbage garden, Republic of Korea and was characterized using a polyphasic approach. Cells were Gram-staining negative, rod-shaped, yellowish orange colored, and motile. The strain was aerobic, catalase and oxidase are positive, and optimum growth temperature and pH were 28 °C and 6.5, respectively. Flexirubin-type pigments were found to be present. On the basis of 16S rRNA gene sequence analysis, strain MAH-10T belongs to the genus Flavobacterium and is most closely related to Flavobacterium tyrosinilyticum KCTC 42726T (98.7%). On the basis of phylogenetic tree, other closely related species are Flavobacterium banpakuense KACC 14225T (98.3%) and Flavobacterium chungbukense KACC 15048T (97.6%). In DNA-DNA hybridization tests, the DNA relatedness between strain MAH-10T and its closest phylogenetic neighbor was below 45.0%. The DNA G+C content was 37.2 mol% and the predominant respiratory quinone was menaquinone-6. The major cellular fatty acids were C15:0 iso, C16:0, and summed feature 3 (C16:1ω7c and/or C16:1ω6c). On the basis of DNA-DNA hybridization results and genotypic, chemotaxonomic, and physiological data analysis, it is demonstrated that strain MAH-10T represented a novel species within the genus Flavobacterium, for which the name Flavobacterium chungangensis is proposed. The type strain is MAH-10T (=KACC 19296T=CGMCC 1.16226T). The NCBI GenBank accession number for the 16S rRNA gene sequence of strain MAH-10T is KY964277 and the digital protologue database (DPD) Taxon Number of strain MAH-10T is TA00296.}, } @article {pmid29464360, year = {2018}, author = {Ai, C and Liang, Y and Miao, B and Chen, M and Zeng, W and Qiu, G}, title = {Identification and Analysis of a Novel Gene Cluster Involves in Fe2+ Oxidation in Acidithiobacillus ferrooxidans ATCC 23270, a Typical Biomining Acidophile.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {818-826}, pmid = {29464360}, issn = {1432-0991}, support = {31470230//National Natural Science Foundation of China (CN)/ ; 51320105006//National Natural Science Foundation of China/ ; 51604308//National Natural Science Foundation of China/ ; }, mesh = {Acidithiobacillus/genetics/*metabolism ; Amino Acid Sequence ; Bacterial Proteins/*genetics/metabolism ; Cytochromes c/metabolism ; Ferrous Compounds/*metabolism ; Gene Expression Regulation, Bacterial ; Molecular Sequence Data ; *Multigene Family ; Operon ; Oxidation-Reduction ; Phylogeny ; Sequence Alignment ; Sulfur/metabolism ; }, abstract = {Iron-oxidizing Acidithiobacillus spp. are applied worldwide in biomining industry to extract metals from sulfide minerals. They derive energy for survival through Fe2+ oxidation and generate Fe3+ for the dissolution of sulfide minerals. However, molecular mechanisms of their iron oxidation still remain elusive. A novel two-cytochrome-encoding gene cluster (named tce gene cluster) encoding a high-molecular-weight cytochrome c (AFE_1428) and a c4-type cytochrome c552 (AFE_1429) in A. ferrooxidans ATCC 23270 was first identified in this study. Bioinformatic analysis together with transcriptional study showed that AFE_1428 and AFE_1429 were the corresponding paralog of Cyc2 (AFE_3153) and Cyc1 (AFE_3152) which were encoded by the extensively studied rus operon and had been proven involving in ferrous iron oxidation. Both AFE_1428 and AFE_1429 contained signal peptide and the classic heme-binding motif(s) as their corresponding paralog. The modeled structure of AFE_1429 showed high resemblance to Cyc1. AFE_1428 and AFE_1429 were preferentially transcribed as their corresponding paralogs in the presence of ferrous iron as sole energy source as compared with sulfur. The tce gene cluster is highly conserved in the genomes of four phylogenetic-related A. ferrooxidans strains that were originally isolated from different sites separated with huge geographical distance, which further implies the importance of this gene cluster. Collectively, AFE_1428 and AFE_1429 involve in Fe2+ oxidation like their corresponding paralog by integrating with the metalloproteins encoded by rus operon. This study provides novel insights into the Fe2+ oxidation mechanism in Fe2+-oxidizing A. ferrooxidans ssp.}, } @article {pmid29463927, year = {2018}, author = {Shaman, J}, title = {Pandemic preparedness and forecast.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {265-267}, doi = {10.1038/s41564-018-0117-7}, pmid = {29463927}, issn = {2058-5276}, } @article {pmid29463926, year = {2018}, author = {Rubin, EJ}, title = {TB diagnosis from the Dark Ages to fluorescence.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {268-269}, doi = {10.1038/s41564-018-0118-6}, pmid = {29463926}, issn = {2058-5276}, } @article {pmid29463925, year = {2018}, author = {Landeta, C and Boyd, D and Beckwith, J}, title = {Disulfide bond formation in prokaryotes.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {270-280}, doi = {10.1038/s41564-017-0106-2}, pmid = {29463925}, issn = {2058-5276}, abstract = {Interest in protein disulfide bond formation has recently increased because of the prominent role of disulfide bonds in bacterial virulence and survival. The first discovered pathway that introduces disulfide bonds into cell envelope proteins consists of Escherichia coli enzymes DsbA and DsbB. Since its discovery, variations on the DsbAB pathway have been found in bacteria and archaea, probably reflecting specific requirements for survival in their ecological niches. One variation found amongst Actinobacteria and Cyanobacteria is the replacement of DsbB by a homologue of human vitamin K epoxide reductase. Many Gram-positive bacteria express enzymes involved in disulfide bond formation that are similar, but non-homologous, to DsbAB. While bacterial pathways promote disulfide bond formation in the bacterial cell envelope, some archaeal extremophiles express proteins with disulfide bonds both in the cytoplasm and in the extra-cytoplasmic space, possibly to stabilize proteins in the face of extreme conditions, such as growth at high temperatures. Here, we summarize the diversity of disulfide-bond-catalysing systems across prokaryotic lineages, discuss examples for understanding the biological basis of such systems, and present perspectives on how such systems are enabling advances in biomedical engineering and drug development.}, } @article {pmid29463924, year = {2018}, author = {Edraki, A and Sontheimer, EJ}, title = {CRISPRs from scratch.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {261-262}, doi = {10.1038/s41564-018-0115-9}, pmid = {29463924}, issn = {2058-5276}, } @article {pmid29463923, year = {2018}, author = {Einsle, O}, title = {Another twist on nitrogenases.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {263-264}, doi = {10.1038/s41564-018-0116-8}, pmid = {29463923}, issn = {2058-5276}, } @article {pmid29463922, year = {2018}, author = {Barlow, G}, title = {Clinical challenges in antimicrobial resistance.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {258-260}, doi = {10.1038/s41564-018-0121-y}, pmid = {29463922}, issn = {2058-5276}, } @article {pmid29463921, year = {2018}, author = {}, title = {Accelerating efforts to end TB.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {257}, doi = {10.1038/s41564-018-0126-6}, pmid = {29463921}, issn = {2058-5276}, } @article {pmid29463780, year = {2018}, author = {Ornes, S}, title = {Science and Culture: Quantum games aim to demystify heady science.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1667-1669}, pmid = {29463780}, issn = {1091-6490}, mesh = {Computer Simulation ; Culture ; Humans ; Quantum Theory ; Science/education/*instrumentation ; *Video Games ; }, } @article {pmid29463764, year = {2018}, author = {Kravats, AN and Hoskins, JR and Reidy, M and Johnson, JL and Doyle, SM and Genest, O and Masison, DC and Wickner, S}, title = {Functional and physical interaction between yeast Hsp90 and Hsp70.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2210-E2219}, pmid = {29463764}, issn = {1091-6490}, support = {P30 GM103324/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/chemistry/genetics/*metabolism ; Amino Acid Motifs ; HSP70 Heat-Shock Proteins/chemistry/genetics/*metabolism ; HSP90 Heat-Shock Proteins/chemistry/genetics/*metabolism ; Heat-Shock Proteins/genetics/metabolism ; Models, Molecular ; Mutation ; Protein Binding ; Saccharomyces cerevisiae/chemistry/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; }, abstract = {Heat shock protein 90 (Hsp90) is a highly conserved ATP-dependent molecular chaperone that is essential in eukaryotes. It is required for the activation and stabilization of more than 200 client proteins, including many kinases and steroid hormone receptors involved in cell-signaling pathways. Hsp90 chaperone activity requires collaboration with a subset of the many Hsp90 cochaperones, including the Hsp70 chaperone. In higher eukaryotes, the collaboration between Hsp90 and Hsp70 is indirect and involves Hop, a cochaperone that interacts with both Hsp90 and Hsp70. Here we show that yeast Hsp90 (Hsp82) and yeast Hsp70 (Ssa1), directly interact in vitro in the absence of the yeast Hop homolog (Sti1), and identify a region in the middle domain of yeast Hsp90 that is required for the interaction. In vivo results using Hsp90 substitution mutants showed that several residues in this region were important or essential for growth at high temperature. Moreover, mutants in this region were defective in interaction with Hsp70 in cell lysates. In vitro, the purified Hsp82 mutant proteins were defective in direct physical interaction with Ssa1 and in protein remodeling in collaboration with Ssa1 and cochaperones. This region of Hsp90 is also important for interactions with several Hsp90 cochaperones and client proteins, suggesting that collaboration between Hsp70 and Hsp90 in protein remodeling may be modulated through competition between Hsp70 and Hsp90 cochaperones for the interaction surface.}, } @article {pmid29463763, year = {2018}, author = {Swatek, KN and Aumayr, M and Pruneda, JN and Visser, LJ and Berryman, S and Kueck, AF and Geurink, PP and Ovaa, H and van Kuppeveld, FJM and Tuthill, TJ and Skern, T and Komander, D}, title = {Irreversible inactivation of ISG15 by a viral leader protease enables alternative infection detection strategies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2371-2376}, pmid = {29463763}, issn = {1091-6490}, support = {309756//European Research Council/International ; MC_U105192732//Medical Research Council/United Kingdom ; //Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Crystallography ; *Cytokines/chemistry/metabolism ; *Endopeptidases/chemistry/metabolism ; HeLa Cells ; Host-Pathogen Interactions ; Humans ; Models, Molecular ; Protein Binding ; Substrate Specificity ; Ubiquitin/*metabolism ; *Ubiquitins/chemistry/metabolism ; }, abstract = {In response to viral infection, cells mount a potent inflammatory response that relies on ISG15 and ubiquitin posttranslational modifications. Many viruses use deubiquitinases and deISGylases that reverse these modifications and antagonize host signaling processes. We here reveal that the leader protease, Lbpro, from foot-and-mouth disease virus (FMDV) targets ISG15 and to a lesser extent, ubiquitin in an unprecedented manner. Unlike canonical deISGylases that hydrolyze the isopeptide linkage after the C-terminal GlyGly motif, Lbpro cleaves the peptide bond preceding the GlyGly motif. Consequently, the GlyGly dipeptide remains attached to the substrate Lys, and cleaved ISG15 is rendered incompetent for reconjugation. A crystal structure of Lbpro bound to an engineered ISG15 suicide probe revealed the molecular basis for ISG15 proteolysis. Importantly, anti-GlyGly antibodies, developed for ubiquitin proteomics, are able to detect Lbpro cleavage products during viral infection. This opens avenues for infection detection of FMDV based on an immutable, host-derived epitope.}, } @article {pmid29463762, year = {2018}, author = {Depersin, J and Barthelemy, M}, title = {From global scaling to the dynamics of individual cities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2317-2322}, pmid = {29463762}, issn = {1091-6490}, mesh = {Automobile Driving/statistics & numerical data ; *Cities/history/statistics & numerical data ; History, 20th Century ; History, 21st Century ; Humans ; *Models, Statistical ; Motor Vehicles ; *Population Density ; *Population Dynamics/history/statistics & numerical data ; United States ; *Urban Population/history/statistics & numerical data ; }, abstract = {Scaling has been proposed as a powerful tool to analyze the properties of complex systems and in particular for cities where it describes how various properties change with population. The empirical study of scaling on a wide range of urban datasets displays apparent nonlinear behaviors whose statistical validity and meaning were recently the focus of many debates. We discuss here another aspect, which is the implication of such scaling forms on individual cities and how they can be used for predicting the behavior of a city when its population changes. We illustrate this discussion in the case of delay due to traffic congestion with a dataset of 101 US cities in the years 1982-2014. We show that the scaling form obtained by agglomerating all of the available data for different cities and for different years does display a nonlinear behavior, but which appears to be unrelated to the dynamics of individual cities when their population grows. In other words, the congestion-induced delay in a given city does not depend on its population only, but also on its previous history. This strong path dependency prohibits the existence of a simple scaling form valid for all cities and shows that we cannot always agglomerate the data for many different systems. More generally, these results also challenge the use of transversal data for understanding longitudinal series for cities.}, } @article {pmid29463761, year = {2018}, author = {Mazin, PV and Shagimardanova, E and Kozlova, O and Cherkasov, A and Sutormin, R and Stepanova, VV and Stupnikov, A and Logacheva, M and Penin, A and Sogame, Y and Cornette, R and Tokumoto, S and Miyata, Y and Kikawada, T and Gelfand, MS and Gusev, O}, title = {Cooption of heat shock regulatory system for anhydrobiosis in the sleeping chironomid Polypedilum vanderplanki.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2477-E2486}, pmid = {29463761}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Chironomidae/genetics/*physiology ; Dehydration ; Female ; Heat Shock Transcription Factors/genetics/*metabolism ; Heat-Shock Response ; Insect Proteins/genetics/*metabolism ; Male ; Stress, Physiological ; }, abstract = {Polypedilum vanderplanki is a striking and unique example of an insect that can survive almost complete desiccation. Its genome and a set of dehydration-rehydration transcriptomes, together with the genome of Polypedilum nubifer (a congeneric desiccation-sensitive midge), were recently released. Here, using published and newly generated datasets reflecting detailed transcriptome changes during anhydrobiosis, as well as a developmental series, we show that the TCTAGAA DNA motif, which closely resembles the binding motif of the Drosophila melanogaster heat shock transcription activator (Hsf), is significantly enriched in the promoter regions of desiccation-induced genes in P. vanderplanki, such as genes encoding late embryogenesis abundant (LEA) proteins, thioredoxins, or trehalose metabolism-related genes, but not in P. nubifer Unlike P. nubifer, P. vanderplanki has double TCTAGAA sites upstream of the Hsf gene itself, which is probably responsible for the stronger activation of Hsf in P. vanderplanki during desiccation compared with P. nubifer To confirm the role of Hsf in desiccation-induced gene activation, we used the Pv11 cell line, derived from P. vanderplanki embryo. After preincubation with trehalose, Pv11 cells can enter anhydrobiosis and survive desiccation. We showed that Hsf knockdown suppresses trehalose-induced activation of multiple predicted Hsf targets (including P. vanderplanki-specific LEA protein genes) and reduces the desiccation survival rate of Pv11 cells fivefold. Thus, cooption of the heat shock regulatory system has been an important evolutionary mechanism for adaptation to desiccation in P. vanderplanki.}, } @article {pmid29463760, year = {2018}, author = {Heldt, FS and Barr, AR and Cooper, S and Bakal, C and Novák, B}, title = {A comprehensive model for the proliferation-quiescence decision in response to endogenous DNA damage in human cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2532-2537}, pmid = {29463760}, issn = {1091-6490}, support = {BB/M00354X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {*Cell Cycle/genetics/physiology ; *Cell Proliferation/genetics/physiology ; Cells, Cultured ; Cyclin-Dependent Kinase Inhibitor p21/genetics/metabolism ; *DNA Damage/genetics/physiology ; Gene Knockout Techniques ; Humans ; Mitogens/genetics/metabolism ; *Models, Biological ; Single-Cell Analysis ; }, abstract = {Human cells that suffer mild DNA damage can enter a reversible state of growth arrest known as quiescence. This decision to temporarily exit the cell cycle is essential to prevent the propagation of mutations, and most cancer cells harbor defects in the underlying control system. Here we present a mechanistic mathematical model to study the proliferation-quiescence decision in nontransformed human cells. We show that two bistable switches, the restriction point (RP) and the G1/S transition, mediate this decision by integrating DNA damage and mitogen signals. In particular, our data suggest that the cyclin-dependent kinase inhibitor p21 (Cip1/Waf1), which is expressed in response to DNA damage, promotes quiescence by blocking positive feedback loops that facilitate G1 progression downstream of serum stimulation. Intriguingly, cells exploit bistability in the RP to convert graded p21 and mitogen signals into an all-or-nothing cell-cycle response. The same mechanism creates a window of opportunity where G1 cells that have passed the RP can revert to quiescence if exposed to DNA damage. We present experimental evidence that cells gradually lose this ability to revert to quiescence as they progress through G1 and that the onset of rapid p21 degradation at the G1/S transition prevents this response altogether, insulating S phase from mild, endogenous DNA damage. Thus, two bistable switches conspire in the early cell cycle to provide both sensitivity and robustness to external stimuli.}, } @article {pmid29463759, year = {2018}, author = {Risner, ML and Pasini, S and Cooper, ML and Lambert, WS and Calkins, DJ}, title = {Axogenic mechanism enhances retinal ganglion cell excitability during early progression in glaucoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2393-E2402}, pmid = {29463759}, issn = {1091-6490}, support = {R01 EY021833/EY/NEI NIH HHS/United States ; P30 EY008126/EY/NEI NIH HHS/United States ; UL1 RR024975/RR/NCRR NIH HHS/United States ; R01 EY024997/EY/NEI NIH HHS/United States ; R01 EY017427/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Axons/*physiology ; Dendrites/physiology ; Disease Progression ; Glaucoma/pathology/*physiopathology ; Humans ; Intraocular Pressure ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred DBA ; Nerve Degeneration ; Optic Nerve/physiopathology ; Retinal Ganglion Cells/pathology/*physiology ; }, abstract = {Diseases of the brain involve early axon dysfunction that often precedes outright degeneration. Pruning of dendrites and their synapses represents a potential driver of axonopathy by reducing activity. Optic nerve degeneration in glaucoma, the world's leading cause of irreversible blindness, involves early stress to retinal ganglion cell (RGC) axons from sensitivity to intraocular pressure (IOP). This sensitivity also influences survival of RGC dendrites and excitatory synapses in the retina. Here we tested in individual RGCs identified by type the relationship between dendritic organization and axon signaling to light following modest, short-term elevations in pressure. We found dendritic pruning occurred early, by 2 wk of elevation, and independent of whether the RGC responded to light onset (ON cells) or offset (OFF cells). Pruning was similarly independent of ON and OFF in the DBA/2J mouse, a chronic glaucoma model. Paradoxically, all RGCs, even those with significant pruning, demonstrated a transient increase in axon firing in response to the preferred light stimulus that occurred on a backdrop of generally enhanced excitability. The increased response was not through conventional presynaptic signaling, but rather depended on voltage-sensitive sodium channels that increased transiently in the axon. Pruning, axon dysfunction, and deficits in visual acuity did not progress between 2 and 4 wk of elevation. These results suggest neurodegeneration in glaucoma involves an early axogenic response that counters IOP-related stress to excitatory dendritic architecture to slow progression and maintain signaling to the brain. Thus, short-term exposure to elevated IOP may precondition the neural system to further insult.}, } @article {pmid29463758, year = {2018}, author = {Viegas, J}, title = {Profile of Michael Strand.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2264-2266}, pmid = {29463758}, issn = {1091-6490}, mesh = {Aedes/genetics/metabolism/microbiology ; Alberta ; Animals ; *Entomology/history/organization & administration ; Female ; History, 20th Century ; History, 21st Century ; *Host-Parasite Interactions ; Humans ; Larva/genetics/growth & development/metabolism/microbiology ; London ; Male ; United States ; Wasps/physiology ; }, } @article {pmid29463757, year = {2018}, author = {Lauer, SA and Sakrejda, K and Ray, EL and Keegan, LT and Bi, Q and Suangtho, P and Hinjoy, S and Iamsirithaworn, S and Suthachana, S and Laosiritaworn, Y and Cummings, DAT and Lessler, J and Reich, NG}, title = {Prospective forecasts of annual dengue hemorrhagic fever incidence in Thailand, 2010-2014.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2175-E2182}, pmid = {29463757}, issn = {1091-6490}, support = {R01 AI102939/AI/NIAID NIH HHS/United States ; R01 AI114703/AI/NIAID NIH HHS/United States ; R35 GM119582/GM/NIGMS NIH HHS/United States ; U54 GM088491/GM/NIGMS NIH HHS/United States ; }, mesh = {Forecasting ; Humans ; Incidence ; *Models, Statistical ; Severe Dengue/*epidemiology ; Thailand/epidemiology ; }, abstract = {Dengue hemorrhagic fever (DHF), a severe manifestation of dengue viral infection that can cause severe bleeding, organ impairment, and even death, affects between 15,000 and 105,000 people each year in Thailand. While all Thai provinces experience at least one DHF case most years, the distribution of cases shifts regionally from year to year. Accurately forecasting where DHF outbreaks occur before the dengue season could help public health officials prioritize public health activities. We develop statistical models that use biologically plausible covariates, observed by April each year, to forecast the cumulative DHF incidence for the remainder of the year. We perform cross-validation during the training phase (2000-2009) to select the covariates for these models. A parsimonious model based on preseason incidence outperforms the 10-y median for 65% of province-level annual forecasts, reduces the mean absolute error by 19%, and successfully forecasts outbreaks (area under the receiver operating characteristic curve = 0.84) over the testing period (2010-2014). We find that functions of past incidence contribute most strongly to model performance, whereas the importance of environmental covariates varies regionally. This work illustrates that accurate forecasts of dengue risk are possible in a policy-relevant timeframe.}, } @article {pmid29463756, year = {2018}, author = {Alder, JK and Hanumanthu, VS and Strong, MA and DeZern, AE and Stanley, SE and Takemoto, CM and Danilova, L and Applegate, CD and Bolton, SG and Mohr, DW and Brodsky, RA and Casella, JF and Greider, CW and Jackson, JB and Armanios, M}, title = {Diagnostic utility of telomere length testing in a hospital-based setting.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2358-E2365}, pmid = {29463756}, issn = {1091-6490}, support = {R01 CA160433/CA/NCI NIH HHS/United States ; T32 GM007309/GM/NIGMS NIH HHS/United States ; K23 HL123601/HL/NHLBI NIH HHS/United States ; R37 AG009383/AG/NIA NIH HHS/United States ; R01 HL119476/HL/NHLBI NIH HHS/United States ; R00 HL113105/HL/NHLBI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Hospitals/statistics & numerical data ; Humans ; In Situ Hybridization, Fluorescence ; Infant ; Male ; Middle Aged ; Mutation ; Pulmonary Emphysema/diagnosis/genetics/*metabolism ; Pulmonary Fibrosis/diagnosis/genetics/*metabolism ; Telomerase/genetics/metabolism ; Telomere/chemistry/*metabolism ; *Telomere Shortening ; Young Adult ; }, abstract = {Telomere length (TL) predicts the onset of cellular senescence in vitro but the diagnostic utility of TL measurement in clinical settings is not fully known. We tested the value of TL measurement by flow cytometry and FISH (flowFISH) in patients with mutations in telomerase and telomere maintenance genes. TL had a discrete and reproducible normal range with definable upper and lower boundaries. While TL above the 50th age-adjusted percentile had a 100% negative predictive value for clinically relevant mutations, the lower threshold in mutation carriers was age-dependent, and adult mutation carriers often overlapped with the lowest decile of controls. The extent of telomere shortening correlated with the age at diagnosis as well as the short telomere syndrome phenotype. Extremely short TL caused bone marrow failure and immunodeficiency in children and young adults, while milder defects manifested as pulmonary fibrosis-emphysema in adults. We prospectively examined whether TL altered treatment decisions for newly diagnosed idiopathic bone marrow failure patients and found abnormally short TL enriched for patients with mutations in some inherited bone marrow failure genes, such as RUNX1, in addition to telomerase and telomere maintenance genes. The result was actionable, altering the choice of treatment regimen and/or hematopoietic stem cell donor in one-fourth of the cases (9 of 38, 24%). We conclude that TL measurement by flowFISH, when used for targeted clinical indications and in limited settings, can influence treatment decisions in ways that improve outcome.}, } @article {pmid29463755, year = {2018}, author = {Pellegrini, P and Fernández, RJ}, title = {Crop intensification, land use, and on-farm energy-use efficiency during the worldwide spread of the green revolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2335-2340}, pmid = {29463755}, issn = {1091-6490}, mesh = {Agriculture/*history/*statistics & numerical data ; Conservation of Natural Resources ; Crop Production/*statistics & numerical data ; *Crops, Agricultural ; *Efficiency ; Farms ; Fertilizers ; Food Supply/statistics & numerical data ; History, 20th Century ; History, 21st Century ; Humans ; Models, Statistical ; }, abstract = {We analyzed crop production, physical inputs, and land use at the country level to assess technological changes behind the threefold increase in global crop production from 1961 to 2014. We translated machinery, fuel, and fertilizer to embedded energy units that, when summed up, provided a measure of agricultural intensification (human subsidy per hectare) for crops in the 58 countries responsible for 95% of global production. Worldwide, there was a 137% increase in input use per hectare, reaching 13 EJ, or 2.6% of the world's primary energy supply, versus only a 10% increase in land use. Intensification was marked in Asia and Latin America, where input-use levels reached those that North America and Europe had in the earlier years of the period; the increase was more accentuated, irrespective of continent, for the 12 countries with mostly irrigated production. Half of the countries (28/58), mainly developed ones, had an average subsidy >5 GJ/ha/y (with fertilizers accounting for 27% in 1961 and 45% in 2014), with most of them (23/28) using about the same area or less than in 1961 (net land sparing of 31 Mha). Most of the remaining countries (24/30 with inputs <5 GJ/ha/y), mainly developing ones, increased their cropped area (net land extensification of 135 Mha). Overall, energy-use efficiency (crop output/inputs) followed a U-shaped trajectory starting at about 3 and finishing close to 4. The prospects of a more sustainable intensification are discussed, and the inadequacy of the land-sparing model expectation of protecting wilderness via intensified agriculture is highlighted.}, } @article {pmid29463754, year = {2018}, author = {Robichaud, N and Hsu, BE and Istomine, R and Alvarez, F and Blagih, J and Ma, EH and Morales, SV and Dai, DL and Li, G and Souleimanova, M and Guo, Q and Del Rincon, SV and Miller, WH and Ramón Y Cajal, S and Park, M and Jones, RG and Piccirillo, CA and Siegel, PM and Sonenberg, N}, title = {Translational control in the tumor microenvironment promotes lung metastasis: Phosphorylation of eIF4E in neutrophils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2202-E2209}, pmid = {29463754}, issn = {1091-6490}, support = {FDN-148423//CIHR/Canada ; PJT-148821//CIHR/Canada ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Amino Acid Motifs ; Animals ; Breast Neoplasms/genetics/metabolism/*pathology ; Cell Line, Tumor ; Eukaryotic Initiation Factor-4E/chemistry/*genetics/*metabolism ; Female ; Humans ; Lung Neoplasms/genetics/*metabolism/pathology/*secondary ; Mice ; Mice, Inbred BALB C ; Mice, SCID ; Myeloid Cell Leukemia Sequence 1 Protein/genetics/metabolism ; Neoplasm Metastasis ; Neutrophils/*metabolism ; Phosphorylation ; *Protein Biosynthesis ; Proto-Oncogene Proteins c-bcl-2/genetics/metabolism ; RNA, Messenger/genetics/metabolism ; *Tumor Microenvironment ; }, abstract = {The translation of mRNAs into proteins serves as a critical regulatory event in gene expression. In the context of cancer, deregulated translation is a hallmark of transformation, promoting the proliferation, survival, and metastatic capabilities of cancer cells. The best-studied factor involved in the translational control of cancer is the eukaryotic translation initiation factor 4E (eIF4E). We and others have shown that eIF4E availability and phosphorylation promote metastasis in mouse models of breast cancer by selectively augmenting the translation of mRNAs involved in invasion and metastasis. However, the impact of translational control in cell types within the tumor microenvironment (TME) is unknown. Here, we demonstrate that regulatory events affecting translation in cells of the TME impact cancer progression. Mice bearing a mutation in the phosphorylation site of eIF4E (S209A) in cells comprising the TME are resistant to the formation of lung metastases in a syngeneic mammary tumor model. This is associated with reduced survival of prometastatic neutrophils due to decreased expression of the antiapoptotic proteins BCL2 and MCL1. Furthermore, we demonstrate that pharmacological inhibition of eIF4E phosphorylation prevents metastatic progression in vivo, supporting the development of phosphorylation inhibitors for clinical use.}, } @article {pmid29463753, year = {2018}, author = {Yolitz, J and Schwing, C and Chang, J and Van Ryk, D and Nawaz, F and Wei, D and Cicala, C and Arthos, J and Fauci, AS}, title = {Signal peptide of HIV envelope protein impacts glycosylation and antigenicity of gp120.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2443-2448}, pmid = {29463753}, issn = {1091-6490}, mesh = {Antibodies, Monoclonal/metabolism ; Dendritic Cells ; Glycosylation ; *HIV Envelope Protein gp120/chemistry/genetics/immunology/metabolism ; HIV-1/immunology ; Protein Sorting Signals/*genetics ; *Recombinant Fusion Proteins/chemistry/genetics/immunology/metabolism ; }, abstract = {The HIV-1 envelope protein (Env) of early-replicating viruses encodes several distinct transmission signatures. One such signature involves a reduced number of potential N-linked glycosylation sites (PNGs). This transmission signature underscores the importance of posttranslational modifications in the fitness of early-replicating isolates. An additional signature in Env involves the overrepresentation of basic amino acid residues at a specific position in the Env signal peptide (SP). In this report, we investigated the potential impact of this SP signature on gp120 glycosylation and antigenicity. Two recombinant gp120s were constructed, one derived from an isolate that lacks this signature and a second from an early-replicating isolate that includes this signature. Chimeric gp120s were also constructed in which the two SPs were swapped between the isolates. All four gp120s were probed with glycan-, structure- and receptor- specific probes in a surface plasmon resonance binding assay. We found that the SP of Env influences qualitative aspects of Env glycosylation that in turn affect the antigenicity of Env in a major way. The SP impacts the affinity of Env for DC-SIGN, a lectin receptor expressed on dendritic cells that is believed to play a role in mucosal transmission. Additionally, affinity for the monoclonal antibodies 17b and A32, which recognize a CD4-induced, open conformation of Env is also altered. These results demonstrate that natural variation in the SP of HIV Env can significantly impact the antigenicity of mature gp120. Thus, the SP is likely subject to antibody-mediated immune pressure.}, } @article {pmid29463752, year = {2018}, author = {Lin, L and Lindsey, M}, title = {Variational structure of Luttinger-Ward formalism and bold diagrammatic expansion for Euclidean lattice field theory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2282-2286}, pmid = {29463752}, issn = {1091-6490}, abstract = {The Luttinger-Ward functional was proposed more than five decades ago and has been used to formally justify most practically used Green's function methods for quantum many-body systems. Nonetheless, the very existence of the Luttinger-Ward functional has been challenged by recent theoretical and numerical evidence. We provide a rigorously justified Luttinger-Ward formalism, in the context of Euclidean lattice field theory. Using the Luttinger-Ward functional, the free energy can be variationally minimized with respect to Green's functions in its domain. We then derive the widely used bold diagrammatic expansion rigorously, without relying on formal arguments such as partial resummation of bare diagrams to infinite order.}, } @article {pmid29463751, year = {2018}, author = {Collins, AGE and Frank, MJ}, title = {Within- and across-trial dynamics of human EEG reveal cooperative interplay between reinforcement learning and working memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2502-2507}, pmid = {29463751}, issn = {1091-6490}, support = {S10 OD016366/OD/NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Algorithms ; Computer Simulation ; *Electroencephalography ; Female ; Humans ; Learning/*physiology ; Male ; Memory, Short-Term/*physiology ; *Models, Neurological ; *Reinforcement (Psychology) ; Reward ; Young Adult ; }, abstract = {Learning from rewards and punishments is essential to survival and facilitates flexible human behavior. It is widely appreciated that multiple cognitive and reinforcement learning systems contribute to decision-making, but the nature of their interactions is elusive. Here, we leverage methods for extracting trial-by-trial indices of reinforcement learning (RL) and working memory (WM) in human electro-encephalography to reveal single-trial computations beyond that afforded by behavior alone. Neural dynamics confirmed that increases in neural expectation were predictive of reduced neural surprise in the following feedback period, supporting central tenets of RL models. Within- and cross-trial dynamics revealed a cooperative interplay between systems for learning, in which WM contributes expectations to guide RL, despite competition between systems during choice. Together, these results provide a deeper understanding of how multiple neural systems interact for learning and decision-making and facilitate analysis of their disruption in clinical populations.}, } @article {pmid29463750, year = {2018}, author = {Benedetti, L and Barentine, AES and Messa, M and Wheeler, H and Bewersdorf, J and De Camilli, P}, title = {Light-activated protein interaction with high spatial subcellular confinement.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2238-E2245}, pmid = {29463750}, issn = {1091-6490}, support = {T32 GM008283/GM/NIGMS NIH HHS/United States ; P30 DA018343/DA/NIDA NIH HHS/United States ; R01 DK082700/DK/NIDDK NIH HHS/United States ; P30 DK045735/DK/NIDDK NIH HHS/United States ; R01 NS036251/NS/NINDS NIH HHS/United States ; R37 NS036251/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Basic Helix-Loop-Helix Transcription Factors/chemistry/genetics/*metabolism ; Cryptochromes/chemistry/genetics/*metabolism ; Cytoplasm/chemistry/genetics/metabolism/*radiation effects ; HeLa Cells ; Humans ; Kinetics ; Mice ; Mitochondria/chemistry/genetics/metabolism/radiation effects ; Neurospora crassa/chemistry/metabolism/radiation effects ; Photoreceptors, Microbial/*chemistry/genetics/metabolism ; Protein Binding/*radiation effects ; Protein Multimerization/radiation effects ; }, abstract = {Methods to acutely manipulate protein interactions at the subcellular level are powerful tools in cell biology. Several blue-light-dependent optical dimerization tools have been developed. In these systems one protein component of the dimer (the bait) is directed to a specific subcellular location, while the other component (the prey) is fused to the protein of interest. Upon illumination, binding of the prey to the bait results in its subcellular redistribution. Here, we compared and quantified the extent of light-dependent dimer occurrence in small, subcellular volumes controlled by three such tools: Cry2/CIB1, iLID, and Magnets. We show that both the location of the photoreceptor protein(s) in the dimer pair and its (their) switch-off kinetics determine the subcellular volume where dimer formation occurs and the amount of protein recruited in the illuminated volume. Efficient spatial confinement of dimer to the area of illumination is achieved when the photosensitive component of the dimerization pair is tethered to the membrane of intracellular compartments and when on and off kinetics are extremely fast, as achieved with iLID or Magnets. Magnets and the iLID variants with the fastest switch-off kinetics induce and maintain protein dimerization in the smallest volume, although this comes at the expense of the total amount of dimer. These findings highlight the distinct features of different optical dimerization systems and will be useful guides in the choice of tools for specific applications.}, } @article {pmid29463749, year = {2018}, author = {Tsoi, R and Wu, F and Zhang, C and Bewick, S and Karig, D and You, L}, title = {Metabolic division of labor in microbial systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2526-2531}, pmid = {29463749}, issn = {1091-6490}, support = {R01 GM098642/GM/NIGMS NIH HHS/United States ; R24 DK110492/DK/NIDDK NIH HHS/United States ; }, mesh = {Bacteria/*metabolism ; Biomass ; Kinetics ; *Metabolic Engineering ; *Metabolic Networks and Pathways ; *Microbial Consortia ; Models, Biological ; *Systems Biology ; }, abstract = {Metabolic pathways are often engineered in single microbial populations. However, the introduction of heterologous circuits into the host can create a substantial metabolic burden that limits the overall productivity of the system. This limitation could be overcome by metabolic division of labor (DOL), whereby distinct populations perform different steps in a metabolic pathway, reducing the burden each population will experience. While conceptually appealing, the conditions when DOL is advantageous have not been rigorously established. Here, we have analyzed 24 common architectures of metabolic pathways in which DOL can be implemented. Our analysis reveals general criteria defining the conditions that favor DOL, accounting for the burden or benefit of the pathway activity on the host populations as well as the transport and turnover of enzymes and intermediate metabolites. These criteria can help guide engineering of metabolic pathways and have implications for understanding evolution of natural microbial communities.}, } @article {pmid29463748, year = {2018}, author = {Busse, M and Müller, M and Kimm, MA and Ferstl, S and Allner, S and Achterhold, K and Herzen, J and Pfeiffer, F}, title = {Three-dimensional virtual histology enabled through cytoplasm-specific X-ray stain for microscopic and nanoscopic computed tomography.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2293-2298}, pmid = {29463748}, issn = {1091-6490}, mesh = {Animals ; Coloring Agents/chemistry ; Cytoplasm/*chemistry ; Eosine Yellowish-(YS)/chemistry ; Histological Techniques/*methods ; Imaging, Three-Dimensional/*methods ; Kidney/chemistry/diagnostic imaging ; Mice ; Microscopy ; Nanotechnology/*methods ; X-Ray Microtomography/*methods ; }, abstract = {Many histological methods require staining of the cytoplasm, which provides instrumental details for diagnosis. One major limitation is the production of 2D images obtained by destructive preparation of 3D tissue samples. X-ray absorption micro- and nanocomputed tomography (microCT and nanoCT) allows for a nondestructive investigation of a 3D tissue sample, and thus aids to determine regions of interest for further histological examinations. However, application of microCT and nanoCT to biological samples (e.g., biopsies) is limited by the missing contrast within soft tissue, which is important to visualize morphological details. We describe an eosin-based preparation overcoming the challenges of contrast enhancement and selectivity for certain tissues. The eosin-based staining protocol is suitable for whole-organ staining, which then enables high-resolution microCT imaging of whole organs and nanoCT imaging of smaller tissue pieces retrieved from the original sample. Our results demonstrate suitability of the eosin-based staining method for diagnostic screening of 3D tissue samples without impeding further diagnostics through histological methods.}, } @article {pmid29463747, year = {2018}, author = {Prasse, C and Ford, B and Nomura, DK and Sedlak, DL}, title = {Unexpected transformation of dissolved phenols to toxic dicarbonyls by hydroxyl radicals and UV light.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2311-2316}, pmid = {29463747}, issn = {1091-6490}, support = {P42 ES004705/ES/NIEHS NIH HHS/United States ; }, mesh = {Aldehydes/*chemistry/metabolism ; Animals ; Hydroxyl Radical/*chemistry ; Liver/chemistry/drug effects/metabolism ; Mice ; *Oxidation-Reduction ; *Phenols/chemistry/radiation effects ; Proteins/analysis/chemistry/metabolism ; Proteome/analysis/chemistry/metabolism ; Tyrosine/chemistry/metabolism ; *Ultraviolet Rays ; Water Pollutants, Chemical/chemistry/radiation effects ; *Water Purification ; }, abstract = {Water treatment systems frequently use strong oxidants or UV light to degrade chemicals that pose human health risks. Unfortunately, these treatments can result in the unintended transformation of organic contaminants into toxic products. We report an unexpected reaction through which exposure of phenolic compounds to hydroxyl radicals (•OH) or UV light results in the formation of toxic α,β-unsaturated enedials and oxoenals. We show that these transformation products damage proteins by reacting with lysine and cysteine moieties. We demonstrate that phenolic compounds react with •OH produced by the increasingly popular UV/hydrogen peroxide (H2O2) water treatment process or UV light to form toxic enedials and oxoenals. In addition to raising concerns about potential health risks of oxidative water treatment, our findings suggest the potential for formation of these toxic compounds in sunlit surface waters, atmospheric water, and living cells. For the latter, our findings may be particularly relevant to efforts to understand cellular damage caused by in vivo production of reactive oxygen species. In particular, we demonstrate that exposure of the amino acid tyrosine to •OH yields an electrophilic enedial product that undergoes cross-linking reaction with both lysine and cysteine residues.}, } @article {pmid29463746, year = {2018}, author = {Konrad, M and Pull, CD and Metzler, S and Seif, K and Naderlinger, E and Grasse, AV and Cremer, S}, title = {Ants avoid superinfections by performing risk-adjusted sanitary care.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2782-2787}, pmid = {29463746}, issn = {1091-6490}, mesh = {Animals ; Ants/*microbiology/*physiology ; Beauveria/physiology ; Behavior, Animal ; Grooming ; Host-Pathogen Interactions ; Metarhizium/physiology ; Models, Biological ; }, abstract = {Being cared for when sick is a benefit of sociality that can reduce disease and improve survival of group members. However, individuals providing care risk contracting infectious diseases themselves. If they contract a low pathogen dose, they may develop low-level infections that do not cause disease but still affect host immunity by either decreasing or increasing the host's vulnerability to subsequent infections. Caring for contagious individuals can thus significantly alter the future disease susceptibility of caregivers. Using ants and their fungal pathogens as a model system, we tested if the altered disease susceptibility of experienced caregivers, in turn, affects their expression of sanitary care behavior. We found that low-level infections contracted during sanitary care had protective or neutral effects on secondary exposure to the same (homologous) pathogen but consistently caused high mortality on superinfection with a different (heterologous) pathogen. In response to this risk, the ants selectively adjusted the expression of their sanitary care. Specifically, the ants performed less grooming and more antimicrobial disinfection when caring for nestmates contaminated with heterologous pathogens compared with homologous ones. By modulating the components of sanitary care in this way the ants acquired less infectious particles of the heterologous pathogens, resulting in reduced superinfection. The performance of risk-adjusted sanitary care reveals the remarkable capacity of ants to react to changes in their disease susceptibility, according to their own infection history and to flexibly adjust collective care to individual risk.}, } @article {pmid29463745, year = {2018}, author = {Langlais, D and Cencic, R and Moradin, N and Kennedy, JM and Ayi, K and Brown, LE and Crandall, I and Tarry, MJ and Schmeing, M and Kain, KC and Porco, JA and Pelletier, J and Gros, P}, title = {Rocaglates as dual-targeting agents for experimental cerebral malaria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2366-E2375}, pmid = {29463745}, issn = {1091-6490}, support = {R24 GM111625/GM/NIGMS NIH HHS/United States ; R35 GM118173/GM/NIGMS NIH HHS/United States ; FDN-148366//CIHR/Canada ; }, mesh = {Aglaia/*chemistry ; Animals ; Antimalarials/*administration & dosage ; Disease Models, Animal ; Erythrocytes/parasitology ; Eukaryotic Initiation Factor-4F/genetics/metabolism ; Female ; Humans ; Malaria, Cerebral/*drug therapy/immunology/parasitology ; Mice ; Mice, Inbred C57BL ; Plant Extracts/*administration & dosage ; Plasmodium berghei/drug effects/genetics/metabolism ; Plasmodium falciparum/drug effects/genetics/metabolism ; Protozoan Proteins/genetics/metabolism ; }, abstract = {Cerebral malaria (CM) is a severe and rapidly progressing complication of infection by Plasmodium parasites that is associated with high rates of mortality and morbidity. Treatment options are currently few, and intervention with artemisinin (Art) has limited efficacy, a problem that is compounded by the emergence of resistance to Art in Plasmodium parasites. Rocaglates are a class of natural products derived from plants of the Aglaia genus that have been shown to interfere with eukaryotic initiation factor 4A (eIF4A), ultimately blocking initiation of protein synthesis. Here, we show that the rocaglate CR-1-31B perturbs association of Plasmodium falciparum eIF4A (PfeIF4A) with RNA. CR-1-31B shows potent prophylactic and therapeutic antiplasmodial activity in vivo in mouse models of infection with Plasmodium berghei (CM) and Plasmodium chabaudi (blood-stage malaria), and can also block replication of different clinical isolates of P. falciparum in human erythrocytes infected ex vivo, including drug-resistant P. falciparum isolates. In vivo, a single dosing of CR-1-31B in P. berghei-infected animals is sufficient to provide protection against lethality. CR-1-31B is shown to dampen expression of the early proinflammatory response in myeloid cells in vitro and dampens the inflammatory response in vivo in P. berghei-infected mice. The dual activity of CR-1-31B as an antiplasmodial and as an inhibitor of the inflammatory response in myeloid cells should prove extremely valuable for therapeutic intervention in human cases of CM.}, } @article {pmid29463744, year = {2018}, author = {Zhang, M and Racine, JJ and Lin, Q and Liu, Y and Tang, S and Qin, Q and Qi, T and Riggs, AD and Zeng, D}, title = {MHC-mismatched mixed chimerism restores peripheral tolerance of noncross-reactive autoreactive T cells in NOD mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2329-E2337}, pmid = {29463744}, issn = {1091-6490}, support = {R01 AI066008/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity ; Diabetes Mellitus, Type 1/*genetics/immunology/therapy ; Female ; Humans ; *Major Histocompatibility Complex ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; *Peripheral Tolerance ; Receptors, Antigen, T-Cell/genetics/immunology ; T-Lymphocytes/*immunology/transplantation ; Transplantation Chimera/genetics ; }, abstract = {Autoimmune type 1 diabetes (T1D) and other autoimmune diseases are associated with particular MHC haplotypes and expansion of autoreactive T cells. Induction of MHC-mismatched but not -matched mixed chimerism by hematopoietic cell transplantation effectively reverses autoimmunity in diabetic nonobese diabetic (NOD) mice, even those with established diabetes. As expected, MHC-mismatched mixed chimerism mediates deletion in the thymus of host-type autoreactive T cells that have T-cell receptor (TCR) recognizing (cross-reacting with) donor-type antigen presenting cells (APCs), which have come to reside in the thymus. However, how MHC-mismatched mixed chimerism tolerizes host autoreactive T cells that recognize only self-MHC-peptide complexes remains unknown. Here, using NOD.Rag1-/-BDC2.5 or NOD.Rag1-/-BDC12-4.1 mice that have only noncross-reactive transgenic autoreactive T cells, we show that induction of MHC-mismatched but not -matched mixed chimerism restores immune tolerance of peripheral noncross-reactive autoreactive T cells. MHC-mismatched mixed chimerism results in increased percentages of both donor- and host-type Foxp3+ Treg cells and up-regulated expression of programmed death-ligand 1 (PD-L1) by host-type plasmacytoid dendritic cells (pDCs). Furthermore, adoptive transfer experiments showed that engraftment of donor-type dendritic cells (DCs) and expansion of donor-type Treg cells are required for tolerizing the noncross-reactive autoreactive T cells in the periphery, which are in association with up-regulation of host-type DC expression of PD-L1 and increased percentage of host-type Treg cells. Thus, induction of MHC-mismatched mixed chimerism may establish a peripheral tolerogenic DC and Treg network that actively tolerizes autoreactive T cells, even those with no TCR recognition of the donor APCs.}, } @article {pmid29463743, year = {2018}, author = {Cakar, F and Zingl, FG and Moisi, M and Reidl, J and Schild, S}, title = {In vivo repressed genes of Vibrio cholerae reveal inverse requirements of an H+/Cl- transporter along the gastrointestinal passage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2376-E2385}, pmid = {29463743}, issn = {1091-6490}, mesh = {Acids/metabolism ; Animals ; Antiporters/genetics/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Cholera/*microbiology ; Gastrointestinal Tract/*microbiology ; Gene Expression Regulation, Bacterial ; Humans ; Mice ; Promoter Regions, Genetic ; Vibrio cholerae/genetics/*metabolism ; }, abstract = {The facultative human pathogen Vibrio cholerae changes its transcriptional profile upon oral ingestion by the host to facilitate survival and colonization fitness. Here, we used a modified version of recombination-based in vivo expression technology to investigate gene silencing during the in vivo passage, which has been understudied. Using a murine model of cholera, we screened a V. cholerae transposon library composed of 10,000 randomly generated reporter fusions and identified 101 in vivo repressed (ivr) genes. Our data indicate that constitutive expression of ivr genes reduces colonization fitness, highlighting the necessity to down-regulate these genes in vivo. For example, the ivr gene clcA, encoding an H+/Cl- transporter, could be linked to the acid tolerance response against hydrochloric acid. In a chloride-dependent manner, ClcA facilitates survival under low pH (e.g., the stomach), but its presence becomes detrimental under alkaline conditions (e.g., lower gastrointestinal tract). This pH-dependent clcA expression is controlled by the LysR-type activator AphB, which acts in concert with AphA to initiate the virulence cascade in V. cholerae after oral ingestion. Thus, transcriptional networks dictating induction of virulence factors and the repression of ivr genes overlap to regulate in vivo colonization dynamics. Overall, the results presented herein highlight the impact of spatiotemporal gene silencing in vivo. The molecular characterization of the underlying mechanisms can provide important insights into in vivo physiology and virulence network regulation.}, } @article {pmid29463742, year = {2018}, author = {Schroeder, H and Sikora, M and Gopalakrishnan, S and Cassidy, LM and Maisano Delser, P and Sandoval Velasco, M and Schraiber, JG and Rasmussen, S and Homburger, JR and Ávila-Arcos, MC and Allentoft, ME and Moreno-Mayar, JV and Renaud, G and Gómez-Carballa, A and Laffoon, JE and Hopkins, RJA and Higham, TFG and Carr, RS and Schaffer, WC and Day, JS and Hoogland, M and Salas, A and Bustamante, CD and Nielsen, R and Bradley, DG and Hofman, CL and Willerslev, E}, title = {Origins and genetic legacies of the Caribbean Taino.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2341-2346}, pmid = {29463742}, issn = {1091-6490}, support = {R35 GM124745/GM/NIGMS NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Adult ; American Native Continental Ancestry Group/*genetics ; Archaeology ; Bahamas ; DNA, Ancient ; DNA, Mitochondrial/genetics ; Female ; Genetics, Population ; Genome, Human/*genetics ; Genomics ; Hispanic Americans/genetics ; History, Ancient ; Human Migration/history/*statistics & numerical data ; Humans ; Male ; Paleontology ; Phylogeny ; Young Adult ; }, abstract = {The Caribbean was one of the last parts of the Americas to be settled by humans, but how and when the islands were first occupied remains a matter of debate. Ancient DNA can help answering these questions, but the work has been hampered by poor DNA preservation. We report the genome sequence of a 1,000-year-old Lucayan Taino individual recovered from the site of Preacher's Cave in the Bahamas. We sequenced her genome to 12.4-fold coverage and show that she is genetically most closely related to present-day Arawakan speakers from northern South America, suggesting that the ancestors of the Lucayans originated there. Further, we find no evidence for recent inbreeding or isolation in the ancient genome, suggesting that the Lucayans had a relatively large effective population size. Finally, we show that the native American components in some present-day Caribbean genomes are closely related to the ancient Taino, demonstrating an element of continuity between precontact populations and present-day Latino populations in the Caribbean.}, } @article {pmid29463741, year = {2018}, author = {Kono, M and Yoshida, N and Maeda, K and Tsokos, GC}, title = {Transcriptional factor ICER promotes glutaminolysis and the generation of Th17 cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2478-2483}, pmid = {29463741}, issn = {1091-6490}, support = {R37 AI049954/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autoimmunity ; *Cyclic AMP Response Element Modulator/genetics/metabolism ; Encephalomyelitis, Autoimmune, Experimental/immunology ; *Glutaminase/antagonists & inhibitors/metabolism ; Glutamine/metabolism ; Mice ; Mice, Transgenic ; *Th17 Cells/cytology/immunology/metabolism ; }, abstract = {Glutaminolysis is a well-known source of energy for effector T cells but its contribution to each T cell subset and the mechanisms which are responsible for the control of involved metabolic enzymes are not fully understood. We report that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on glutaminolysis and the up-regulation of glutaminase 1 (Gls1), the first enzyme in the glutaminolysis pathway. Both pharmacological and siRNA-based selective inhibition of Gls1 reduced in vitro Th17 differentiation and reduced the CD3/TCR-mediated increase of the mammalian target of rapamycin complex 1 activity. Treatment of mice with a Gls1 inhibitor ameliorated experimental autoimmune encephalomyelitis. Furthermore, RAG1-deficient mice that received Gls1-shRNA-transfected 2D2 T cells had reduced experimental autoimmune encephalomyelitis scores compared with those that received control-shRNA-treated cells. Next we found that T cells deficient in inducible cAMP early repressor (ICER), a transcriptional factor known to promote Th17 differentiation, display reduced activity of oxidative phosphorylation rates in the presence of glutamine and reduced Gls1 expression, both of which could be restored by ICER overexpression. Finally, we demonstrate that ICER binds to the gls1 promoter directly and increases its activity. These findings demonstrate the importance of glutaminolysis in the generation of Th17 and the direct control of Gls1 activity by the IL-17-promoting transcription factor ICER. Pharmaceutical modulation of the glutaminolysis pathway should be considered to control Th17-mediated pathology.}, } @article {pmid29463740, year = {2018}, author = {}, title = {Correction for Kleist et al., Chronic anthropogenic noise disrupts glucocorticoid signaling and has multiple effects on fitness in an avian community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2145}, doi = {10.1073/pnas.1801328115}, pmid = {29463740}, issn = {1091-6490}, } @article {pmid29463739, year = {2018}, author = {Rugbjerg, P and Sarup-Lytzen, K and Nagy, M and Sommer, MOA}, title = {Synthetic addiction extends the productive life time of engineered Escherichia coli populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2347-2352}, pmid = {29463739}, issn = {1091-6490}, mesh = {Bioreactors/microbiology ; *Escherichia coli/genetics/metabolism/physiology ; Evolution, Molecular ; Fermentation ; Genes, Bacterial/genetics ; Genes, Essential/genetics ; Metabolic Engineering/*methods ; Mevalonic Acid/analysis/metabolism ; Synthetic Biology/*methods ; }, abstract = {Bio-production of chemicals is an important driver of the societal transition toward sustainability. However, fermentations with heavily engineered production organisms can be challenging to scale to industrial volumes. Such fermentations are subject to evolutionary pressures that select for a wide range of genetic variants that disrupt the biosynthetic capacity of the engineered organism. Synthetic product addiction that couples high-yield production of a desired metabolite to expression of nonconditionally essential genes could offer a solution to this problem by selectively favoring cells with biosynthetic capacity in the population without constraining the medium. We constructed such synthetic product addiction by controlling the expression of two nonconditionally essential genes with a mevalonic acid biosensor. The product-addicted production organism retained high-yield mevalonic acid production through 95 generations of cultivation, corresponding to the number of cell generations required for >200-m3 industrial-scale production, at which time the nonaddicted strain completely abolished production. Using deep DNA sequencing, we find that the product-addicted populations do not accumulate genetic variants that compromise biosynthetic capacity, highlighting how synthetic networks can be designed to control genetic population heterogeneity. Such synthetic redesign of evolutionary forces with endogenous processes may be a promising concept for realizing complex cellular designs required for sustainable bio-manufacturing.}, } @article {pmid29463738, year = {2018}, author = {Ramiro, C and Srinivasan, M and Malt, BC and Xu, Y}, title = {Algorithms in the historical emergence of word senses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2323-2328}, pmid = {29463738}, issn = {1091-6490}, mesh = {*Algorithms ; Computational Biology ; Computer Simulation ; England ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; History, Medieval ; Humans ; Language/*history ; *Models, Statistical ; *Psycholinguistics ; *Semantics ; }, abstract = {Human language relies on a finite lexicon to express a potentially infinite set of ideas. A key result of this tension is that words acquire novel senses over time. However, the cognitive processes that underlie the historical emergence of new word senses are poorly understood. Here, we present a computational framework that formalizes competing views of how new senses of a word might emerge by attaching to existing senses of the word. We test the ability of the models to predict the temporal order in which the senses of individual words have emerged, using an historical lexicon of English spanning the past millennium. Our findings suggest that word senses emerge in predictable ways, following an historical path that reflects cognitive efficiency, predominantly through a process of nearest-neighbor chaining. Our work contributes a formal account of the generative processes that underlie lexical evolution.}, } @article {pmid29463737, year = {2018}, author = {Wang, Y and Tang, Z and Huang, H and Li, J and Wang, Z and Yu, Y and Zhang, C and Li, J and Dai, H and Wang, F and Cai, T and Tang, N}, title = {Pulmonary alveolar type I cell population consists of two distinct subtypes that differ in cell fate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2407-2412}, pmid = {29463737}, issn = {1091-6490}, mesh = {*Alveolar Epithelial Cells/cytology/metabolism/physiology ; Animals ; Cell Differentiation ; Cell Lineage/*physiology ; Insulin-Like Growth Factor Binding Protein 2/genetics/metabolism ; Mice ; Mice, Transgenic ; Pulmonary Alveoli/*cytology ; RNA/analysis/genetics/metabolism ; Regeneration/physiology ; Sequence Analysis, RNA ; *Single-Cell Analysis ; Transcriptome/genetics/physiology ; }, abstract = {Pulmonary alveolar type I (AT1) cells cover more than 95% of alveolar surface and are essential for the air-blood barrier function of lungs. AT1 cells have been shown to retain developmental plasticity during alveolar regeneration. However, the development and heterogeneity of AT1 cells remain largely unknown. Here, we conducted a single-cell RNA-seq analysis to characterize postnatal AT1 cell development and identified insulin-like growth factor-binding protein 2 (Igfbp2) as a genetic marker specifically expressed in postnatal AT1 cells. The portion of AT1 cells expressing Igfbp2 increases during alveologenesis and in post pneumonectomy (PNX) newly formed alveoli. We found that the adult AT1 cell population contains both Hopx+Igfbp2+ and Hopx+Igfbp2- AT1 cells, which have distinct cell fates during alveolar regeneration. Using an Igfbp2-CreER mouse model, we demonstrate that Hopx+Igfbp2+ AT1 cells represent terminally differentiated AT1 cells that are not able to transdifferentiate into AT2 cells during post-PNX alveolar regeneration. Our study provides tools and insights that will guide future investigations into the molecular and cellular mechanism or mechanisms underlying AT1 cell fate during lung development and regeneration.}, } @article {pmid29463736, year = {2018}, author = {Beliveau, BJ and Kishi, JY and Nir, G and Sasaki, HM and Saka, SK and Nguyen, SC and Wu, CT and Yin, P}, title = {OligoMiner provides a rapid, flexible environment for the design of genome-scale oligonucleotide in situ hybridization probes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2183-E2192}, pmid = {29463736}, issn = {1091-6490}, support = {DP1 GM106412/GM/NIGMS NIH HHS/United States ; R01 EB018659/EB/NIBIB NIH HHS/United States ; R01 HD091797/HD/NICHD NIH HHS/United States ; U01 MH106011/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Arabidopsis ; DNA/genetics/metabolism ; Data Mining ; Genomics/*methods ; Humans ; In Situ Hybridization, Fluorescence/*methods ; Mice ; Models, Genetic ; Oligonucleotide Probes/*chemistry/*genetics/metabolism ; }, abstract = {Oligonucleotide (oligo)-based FISH has emerged as an important tool for the study of chromosome organization and gene expression and has been empowered by the commercial availability of highly complex pools of oligos. However, a dedicated bioinformatic design utility has yet to be created specifically for the purpose of identifying optimal oligo FISH probe sequences on the genome-wide scale. Here, we introduce OligoMiner, a rapid and robust computational pipeline for the genome-scale design of oligo FISH probes that affords the scientist exact control over the parameters of each probe. Our streamlined method uses standard bioinformatic file formats, allowing users to seamlessly integrate new and existing utilities into the pipeline as desired, and introduces a method for evaluating the specificity of each probe molecule that connects simulated hybridization energetics to rapidly generated sequence alignments using supervised machine learning. We demonstrate the scalability of our approach by performing genome-scale probe discovery in numerous model organism genomes and showcase the performance of the resulting probes with diffraction-limited and single-molecule superresolution imaging of chromosomal and RNA targets. We anticipate that this pipeline will make the FISH probe design process much more accessible and will more broadly facilitate the design of pools of hybridization probes for a variety of applications.}, } @article {pmid29463735, year = {2018}, author = {Huszár, F}, title = {Note on the quadratic penalties in elastic weight consolidation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2496-E2497}, pmid = {29463735}, issn = {1091-6490}, mesh = {*Machine Learning ; }, } @article {pmid29463734, year = {2018}, author = {Kirkpatrick, J and Pascanu, R and Rabinowitz, N and Veness, J and Desjardins, G and Rusu, AA and Milan, K and Quan, J and Ramalho, T and Grabska-Barwinska, A and Hassabis, D and Clopath, C and Kumaran, D and Hadsell, R}, title = {Reply to Huszár: The elastic weight consolidation penalty is empirically valid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2498}, pmid = {29463734}, issn = {1091-6490}, mesh = {*Machine Learning ; }, } @article {pmid29463733, year = {2018}, author = {Leftwich, PT and Clarke, NVE and Hutchings, MI and Chapman, T}, title = {Reply to Rosenberg et al.: Diet, gut bacteria, and assortative mating in Drosophila melanogaster.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2154-E2155}, pmid = {29463733}, issn = {1091-6490}, mesh = {Animals ; Bacteria ; Diet ; *Drosophila melanogaster ; Mating Preference, Animal ; *Reproduction ; }, } @article {pmid29463732, year = {2018}, author = {Rosenberg, E and Zilber-Rosenberg, I and Sharon, G and Segal, D}, title = {Diet-induced mating preference in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2153}, pmid = {29463732}, issn = {1091-6490}, mesh = {Animals ; Diet ; *Drosophila ; Drosophila melanogaster ; *Mating Preference, Animal ; Reproduction ; Sexual Behavior, Animal ; }, } @article {pmid29463731, year = {2018}, author = {Salanenka, Y and Verstraeten, I and Löfke, C and Tabata, K and Naramoto, S and Glanc, M and Friml, J}, title = {Gibberellin DELLA signaling targets the retromer complex to redirect protein trafficking to the plasma membrane.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {14}, pages = {3716-3721}, pmid = {29463731}, issn = {1091-6490}, support = {282300//European Research Council/International ; }, mesh = {Arabidopsis/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cell Membrane/*metabolism ; Gene Expression Regulation, Plant/*drug effects ; Gibberellins/*pharmacology ; Indoleacetic Acids/pharmacology ; Microtubules/metabolism ; Plant Growth Regulators/pharmacology ; Protein Transport ; Signal Transduction ; Sorting Nexins/genetics/metabolism ; Vacuoles/*metabolism ; }, abstract = {The plant hormone gibberellic acid (GA) is a crucial regulator of growth and development. The main paradigm of GA signaling puts forward transcriptional regulation via the degradation of DELLA transcriptional repressors. GA has also been shown to regulate tropic responses by modulation of the plasma membrane incidence of PIN auxin transporters by an unclear mechanism. Here we uncovered the cellular and molecular mechanisms by which GA redirects protein trafficking and thus regulates cell surface functionality. Photoconvertible reporters revealed that GA balances the protein traffic between the vacuole degradation route and recycling back to the cell surface. Low GA levels promote vacuolar delivery and degradation of multiple cargos, including PIN proteins, whereas high GA levels promote their recycling to the plasma membrane. This GA effect requires components of the retromer complex, such as Sorting Nexin 1 (SNX1) and its interacting, microtubule (MT)-associated protein, the Cytoplasmic Linker-Associated Protein (CLASP1). Accordingly, GA regulates the subcellular distribution of SNX1 and CLASP1, and the intact MT cytoskeleton is essential for the GA effect on trafficking. This GA cellular action occurs through DELLA proteins that regulate the MT and retromer presumably via their interaction partners Prefoldins (PFDs). Our study identified a branching of the GA signaling pathway at the level of DELLA proteins, which, in parallel to regulating transcription, also target by a nontranscriptional mechanism the retromer complex acting at the intersection of the degradation and recycling trafficking routes. By this mechanism, GA can redirect receptors and transporters to the cell surface, thus coregulating multiple processes, including PIN-dependent auxin fluxes during tropic responses.}, } @article {pmid29463730, year = {2018}, author = {Bromer, C and Bartol, TM and Bowden, JB and Hubbard, DD and Hanka, DC and Gonzalez, PV and Kuwajima, M and Mendenhall, JM and Parker, PH and Abraham, WC and Sejnowski, TJ and Harris, KM}, title = {Long-term potentiation expands information content of hippocampal dentate gyrus synapses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2410-E2418}, pmid = {29463730}, issn = {1091-6490}, support = {R01 MH079076/MH/NIMH NIH HHS/United States ; R01 MH104319/MH/NIMH NIH HHS/United States ; P41 GM103712/GM/NIGMS NIH HHS/United States ; R01 NS021184/NS/NINDS NIH HHS/United States ; R01 MH095980/MH/NIMH NIH HHS/United States ; R37 NS021184/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Dentate Gyrus/*physiology ; *Long-Term Potentiation ; Male ; Neuronal Plasticity ; Perforant Pathway/physiology ; Rats ; Rats, Long-Evans ; Synapses/*physiology ; }, abstract = {An approach combining signal detection theory and precise 3D reconstructions from serial section electron microscopy (3DEM) was used to investigate synaptic plasticity and information storage capacity at medial perforant path synapses in adult hippocampal dentate gyrus in vivo. Induction of long-term potentiation (LTP) markedly increased the frequencies of both small and large spines measured 30 minutes later. This bidirectional expansion resulted in heterosynaptic counterbalancing of total synaptic area per unit length of granule cell dendrite. Control hemispheres exhibited 6.5 distinct spine sizes for 2.7 bits of storage capacity while LTP resulted in 12.9 distinct spine sizes (3.7 bits). In contrast, control hippocampal CA1 synapses exhibited 4.7 bits with much greater synaptic precision than either control or potentiated dentate gyrus synapses. Thus, synaptic plasticity altered total capacity, yet hippocampal subregions differed dramatically in their synaptic information storage capacity, reflecting their diverse functions and activation histories.}, } @article {pmid29463729, year = {2018}, author = {Heller, J and Clavé, C and Gladieux, P and Saupe, SJ and Glass, NL}, title = {NLR surveillance of essential SEC-9 SNARE proteins induces programmed cell death upon allorecognition in filamentous fungi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2292-E2301}, pmid = {29463729}, issn = {1091-6490}, support = {P01 GM068087/GM/NIGMS NIH HHS/United States ; R01 GM060468/GM/NIGMS NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; *Apoptosis ; Fungal Proteins/chemistry/genetics/*metabolism ; Molecular Sequence Data ; NLR Proteins/chemistry/genetics/*metabolism ; Neurospora crassa/chemistry/cytology/genetics/*metabolism ; Podospora/chemistry/cytology/genetics/*metabolism ; Protein Binding ; Protein Domains ; SNARE Proteins/chemistry/genetics/*metabolism ; Sequence Alignment ; }, abstract = {In plants and metazoans, intracellular receptors that belong to the NOD-like receptor (NLR) family are major contributors to innate immunity. Filamentous fungal genomes contain large repertoires of genes encoding for proteins with similar architecture to plant and animal NLRs with mostly unknown function. Here, we identify and molecularly characterize patatin-like phospholipase-1 (PLP-1), an NLR-like protein containing an N-terminal patatin-like phospholipase domain, a nucleotide-binding domain (NBD), and a C-terminal tetratricopeptide repeat (TPR) domain. PLP-1 guards the essential SNARE protein SEC-9; genetic differences at plp-1 and sec-9 function to trigger allorecognition and cell death in two distantly related fungal species, Neurospora crassa and Podospora anserina Analyses of Neurospora population samples revealed that plp-1 and sec-9 alleles are highly polymorphic, segregate into discrete haplotypes, and show transspecies polymorphism. Upon fusion between cells bearing incompatible sec-9 and plp-1 alleles, allorecognition and cell death are induced, which are dependent upon physical interaction between SEC-9 and PLP-1. The central NBD and patatin-like phospholipase activity of PLP-1 are essential for allorecognition and cell death, while the TPR domain and the polymorphic SNARE domain of SEC-9 function in conferring allelic specificity. Our data indicate that fungal NLR-like proteins function similar to NLR immune receptors in plants and animals, showing that NLRs are major contributors to innate immunity in plants and animals and for allorecognition in fungi.}, } @article {pmid29463728, year = {2018}, author = {}, title = {Correction for Woelders et al., Melanopsin- and L-cone-induced pupil constriction is inhibited by S- and M-cones in humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2147}, doi = {10.1073/pnas.1801001115}, pmid = {29463728}, issn = {1091-6490}, } @article {pmid29463727, year = {2018}, author = {Senges, CHR and Al-Dilaimi, A and Marchbank, DH and Wibberg, D and Winkler, A and Haltli, B and Nowrousian, M and Kalinowski, J and Kerr, RG and Bandow, JE}, title = {The secreted metabolome of Streptomyces chartreusis and implications for bacterial chemistry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2490-2495}, pmid = {29463727}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/chemistry/metabolism ; Deferoxamine/chemistry/metabolism ; Metabolic Networks and Pathways ; Metabolome/*physiology ; Metabolomics ; Models, Molecular ; *Siderophores/chemistry/metabolism ; Streptomyces/*chemistry/*metabolism ; }, abstract = {Actinomycetes are known for producing diverse secondary metabolites. Combining genomics with untargeted data-dependent tandem MS and molecular networking, we characterized the secreted metabolome of the tunicamycin producer Streptomyces chartreusis NRRL 3882. The genome harbors 128 predicted biosynthetic gene clusters. We detected >1,000 distinct secreted metabolites in culture supernatants, only 22 of which were identified based on standards and public spectral libraries. S. chartreusis adapts the secreted metabolome to cultivation conditions. A number of metabolites are produced iron dependently, among them 17 desferrioxamine siderophores aiding in iron acquisition. Eight previously unknown members of this long-known compound class are described. A single desferrioxamine synthesis gene cluster was detected in the genome, yet different sets of desferrioxamines are produced in different media. Additionally, a polyether ionophore, differentially produced by the calcimycin biosynthesis cluster, was discovered. This illustrates that metabolite output of a single biosynthetic machine can be exquisitely regulated not only with regard to product quantity but also with regard to product range. Compared with chemically defined medium, in complex medium, total metabolite abundance was higher, structural diversity greater, and the average molecular weight almost doubled. Tunicamycins, for example, were only produced in complex medium. Extrapolating from this study, we anticipate that the larger part of bacterial chemistry, including chemical structures, ecological functions, and pharmacological potential, is yet to be uncovered.}, } @article {pmid29463726, year = {2018}, author = {Hashiguchi, T and Fukuda, Y and Matsuoka, R and Kuroda, D and Kubota, M and Shirogane, Y and Watanabe, S and Tsumoto, K and Kohda, D and Plemper, RK and Yanagi, Y}, title = {Structures of the prefusion form of measles virus fusion protein in complex with inhibitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2496-2501}, pmid = {29463726}, issn = {1091-6490}, support = {R01 AI071002/AI/NIAID NIH HHS/United States ; R01 HD079327/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Antiviral Agents/chemistry/metabolism ; Binding Sites ; CHO Cells ; Cercopithecus aethiops ; Cricetulus ; Models, Molecular ; *Peptides/chemistry/metabolism ; Vero Cells ; *Viral Fusion Proteins/antagonists & inhibitors/chemistry/metabolism ; }, abstract = {Measles virus (MeV), a major cause of childhood morbidity and mortality, is highly immunotropic and one of the most contagious pathogens. MeV may establish, albeit rarely, persistent infection in the central nervous system, causing fatal and intractable neurodegenerative diseases such as subacute sclerosing panencephalitis and measles inclusion body encephalitis. Recent studies have suggested that particular substitutions in the MeV fusion (F) protein are involved in the pathogenesis by destabilizing the F protein and endowing it with hyperfusogenicity. Here we show the crystal structures of the prefusion MeV-F alone and in complex with the small compound AS-48 or a fusion inhibitor peptide. Notably, these independently developed inhibitors bind the same hydrophobic pocket located at the region connecting the head and stalk of MeV-F, where a number of substitutions in MeV isolates from neurodegenerative diseases are also localized. Since these inhibitors could suppress membrane fusion mediated by most of the hyperfusogenic MeV-F mutants, the development of more effective inhibitors based on the structures may be warranted to treat MeV-induced neurodegenerative diseases.}, } @article {pmid29463725, year = {2018}, author = {Avery, L and Filderman, J and Szymczak-Workman, AL and Kane, LP}, title = {Tim-3 co-stimulation promotes short-lived effector T cells, restricts memory precursors, and is dispensable for T cell exhaustion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2455-2460}, pmid = {29463725}, issn = {1091-6490}, support = {P30 EY008098/EY/NEI NIH HHS/United States ; R01 CA206517/CA/NCI NIH HHS/United States ; R03 AI109605/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chronic Disease ; Hepatitis A Virus Cellular Receptor 2/genetics/*immunology ; Lymphocyte Activation/*immunology ; Lymphocytic Choriomeningitis ; Lymphocytic choriomeningitis virus/immunology ; Mice ; Phenotype ; Receptors, Antigen, T-Cell/immunology ; Signal Transduction/*immunology ; T-Lymphocyte Subsets/*immunology ; TOR Serine-Threonine Kinases/metabolism ; }, abstract = {Tim-3 is highly expressed on a subset of T cells during T cell exhaustion in settings of chronic viral infection and tumors. Using lymphocytic choriomeningitis virus (LCMV) Clone 13, a model for chronic infection, we found that Tim-3 was neither necessary nor sufficient for the development of T cell exhaustion. Nonetheless, expression of Tim-3 was sufficient to drive resistance to PD-L1 blockade therapy during chronic infection. Strikingly, expression of Tim-3 promoted the development of short-lived effector T cells, at the expense of memory precursor development, after acute LCMV infection. These effects were accompanied by increased Akt/mTOR signaling in T cells expressing endogenous or ectopic Tim-3. Conversely, Akt/mTOR signaling was reduced in effector T cells from Tim-3-deficient mice. Thus, Tim-3 is essential for optimal effector T cell responses, and may also contribute to exhaustion by restricting the development of long-lived memory T cells. Taken together, our results suggest that Tim-3 is actually more similar to costimulatory receptors that are up-regulated after T cell activation than to a dominant inhibitory protein like PD-1. These findings have significant implications for the development of anti-Tim-3 antibodies as therapeutic agents.}, } @article {pmid29463724, year = {2018}, author = {Takemoto, K and Ebine, K and Askani, JC and Krüger, F and Gonzalez, ZA and Ito, E and Goh, T and Schumacher, K and Nakano, A and Ueda, T}, title = {Distinct sets of tethering complexes, SNARE complexes, and Rab GTPases mediate membrane fusion at the vacuole in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2457-E2466}, pmid = {29463724}, issn = {1091-6490}, mesh = {Arabidopsis/enzymology/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Endosomes/genetics/metabolism ; Membrane Fusion ; Multiprotein Complexes/genetics/metabolism ; Protein Binding ; SNARE Proteins/genetics/*metabolism ; Vacuoles/enzymology/genetics/*metabolism ; Vesicular Transport Proteins/genetics/metabolism ; rab GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {Membrane trafficking plays pivotal roles in various cellular activities and higher-order functions of eukaryotes and requires tethering factors to mediate contact between transport intermediates and target membranes. Two evolutionarily conserved tethering complexes, homotypic fusion and protein sorting (HOPS) and class C core vacuole/endosome tethering (CORVET), are known to act in endosomal/vacuolar transport in yeast and animals. Both complexes share a core subcomplex consisting of Vps11, Vps18, Vps16, and Vps33, and in addition to this core, HOPS contains Vps39 and Vps41, whereas CORVET contains Vps3 and Vps8. HOPS and CORVET subunits are also conserved in the model plant Arabidopsis. However, vacuolar trafficking in plants occurs through multiple unique transport pathways, and how these conserved tethering complexes mediate endosomal/vacuolar transport in plants has remained elusive. In this study, we investigated the functions of VPS18, VPS3, and VPS39, which are core complex, CORVET-specific, and HOPS-specific subunits, respectively. Impairment of these tethering proteins resulted in embryonic lethality, distinctly altering vacuolar morphology and perturbing transport of a vacuolar membrane protein. CORVET interacted with canonical RAB5 and a plant-specific R-soluble NSF attachment protein receptor (SNARE), VAMP727, which mediates fusion between endosomes and the vacuole, whereas HOPS interacted with RAB7 and another R-SNARE, VAMP713, which likely mediates homotypic vacuolar fusion. These results indicate that CORVET and HOPS act in distinct vacuolar trafficking pathways in plant cells, unlike those of nonplant systems that involve sequential action of these tethering complexes during vacuolar/lysosomal trafficking. These results highlight a unique diversification of vacuolar/lysosomal transport that arose during plant evolution, using evolutionarily conserved tethering components.}, } @article {pmid29463723, year = {2018}, author = {Sun, F and Roderick, ML and Farquhar, GD}, title = {Rainfall statistics, stationarity, and climate change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2305-2310}, pmid = {29463723}, issn = {1091-6490}, abstract = {There is a growing research interest in the detection of changes in hydrologic and climatic time series. Stationarity can be assessed using the autocorrelation function, but this is not yet common practice in hydrology and climate. Here, we use a global land-based gridded annual precipitation (hereafter P) database (1940-2009) and find that the lag 1 autocorrelation coefficient is statistically significant at around 14% of the global land surface, implying nonstationary behavior (90% confidence). In contrast, around 76% of the global land surface shows little or no change, implying stationary behavior. We use these results to assess change in the observed P over the most recent decade of the database. We find that the changes for most (84%) grid boxes are within the plausible bounds of no significant change at the 90% CI. The results emphasize the importance of adequately accounting for natural variability when assessing change.}, } @article {pmid29463722, year = {2018}, author = {Kalms, J and Schmidt, A and Frielingsdorf, S and Utesch, T and Gotthard, G and von Stetten, D and van der Linden, P and Royant, A and Mroginski, MA and Carpentier, P and Lenz, O and Scheerer, P}, title = {Tracking the route of molecular oxygen in O2-tolerant membrane-bound [NiFe] hydrogenase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2229-E2237}, pmid = {29463722}, issn = {1091-6490}, mesh = {Bacterial Proteins/*chemistry/genetics/*metabolism ; Binding Sites ; Catalytic Domain ; Cell Membrane/chemistry/*enzymology/genetics ; Crystallography, X-Ray ; Cupriavidus necator/chemistry/*enzymology/genetics ; Hydrogenase/*chemistry/genetics/*metabolism ; Hydrophobic and Hydrophilic Interactions ; Oxygen/chemistry/*metabolism ; }, abstract = {[NiFe] hydrogenases catalyze the reversible splitting of H2 into protons and electrons at a deeply buried active site. The catalytic center can be accessed by gas molecules through a hydrophobic tunnel network. While most [NiFe] hydrogenases are inactivated by O2, a small subgroup, including the membrane-bound [NiFe] hydrogenase (MBH) of Ralstonia eutropha, is able to overcome aerobic inactivation by catalytic reduction of O2 to water. This O2 tolerance relies on a special [4Fe3S] cluster that is capable of releasing two electrons upon O2 attack. Here, the O2 accessibility of the MBH gas tunnel network has been probed experimentally using a "soak-and-freeze" derivatization method, accompanied by protein X-ray crystallography and computational studies. This combined approach revealed several sites of O2 molecules within a hydrophobic tunnel network leading, via two tunnel entrances, to the catalytic center of MBH. The corresponding site occupancies were related to the O2 concentrations used for MBH crystal derivatization. The examination of the O2-derivatized data furthermore uncovered two unexpected structural alterations at the [4Fe3S] cluster, which might be related to the O2 tolerance of the enzyme.}, } @article {pmid29463721, year = {2018}, author = {Gastner, MT and Seguy, V and More, P}, title = {Fast flow-based algorithm for creating density-equalizing map projections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2156-E2164}, pmid = {29463721}, issn = {1091-6490}, abstract = {Cartograms are maps that rescale geographic regions (e.g., countries, districts) such that their areas are proportional to quantitative demographic data (e.g., population size, gross domestic product). Unlike conventional bar or pie charts, cartograms can represent correctly which regions share common borders, resulting in insightful visualizations that can be the basis for further spatial statistical analysis. Computer programs can assist data scientists in preparing cartograms, but developing an algorithm that can quickly transform every coordinate on the map (including points that are not exactly on a border) while generating recognizable images has remained a challenge. Methods that translate the cartographic deformations into physics-inspired equations of motion have become popular, but solving these equations with sufficient accuracy can still take several minutes on current hardware. Here we introduce a flow-based algorithm whose equations of motion are numerically easier to solve compared with previous methods. The equations allow straightforward parallelization so that the calculation takes only a few seconds even for complex and detailed input. Despite the speedup, the proposed algorithm still keeps the advantages of previous techniques: With comparable quantitative measures of shape distortion, it accurately scales all areas, correctly fits the regions together, and generates a map projection for every point. We demonstrate the use of our algorithm with applications to the 2016 US election results, the gross domestic products of Indian states and Chinese provinces, and the spatial distribution of deaths in the London borough of Kensington and Chelsea between 2011 and 2014.}, } @article {pmid29463720, year = {2018}, author = {Van Eps, N and Altenbach, C and Caro, LN and Latorraca, NR and Hollingsworth, SA and Dror, RO and Ernst, OP and Hubbell, WL}, title = {Gi- and Gs-coupled GPCRs show different modes of G-protein binding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2383-2388}, pmid = {29463720}, issn = {1091-6490}, support = {P30 EY000331/EY/NEI NIH HHS/United States ; R01 EY005216/EY/NEI NIH HHS/United States ; T15 LM007033/LM/NLM NIH HHS/United States ; T32 GM008294/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cattle ; *Heterotrimeric GTP-Binding Proteins/chemistry/genetics/metabolism ; Molecular Dynamics Simulation ; Mutation ; Protein Binding ; Protein Conformation ; *Rhodopsin/chemistry/genetics/metabolism ; Spectrum Analysis ; }, abstract = {More than two decades ago, the activation mechanism for the membrane-bound photoreceptor and prototypical G protein-coupled receptor (GPCR) rhodopsin was uncovered. Upon light-induced changes in ligand-receptor interaction, movement of specific transmembrane helices within the receptor opens a crevice at the cytoplasmic surface, allowing for coupling of heterotrimeric guanine nucleotide-binding proteins (G proteins). The general features of this activation mechanism are conserved across the GPCR superfamily. Nevertheless, GPCRs have selectivity for distinct G-protein family members, but the mechanism of selectivity remains elusive. Structures of GPCRs in complex with the stimulatory G protein, Gs, and an accessory nanobody to stabilize the complex have been reported, providing information on the intermolecular interactions. However, to reveal the structural selectivity filters, it will be necessary to determine GPCR-G protein structures involving other G-protein subtypes. In addition, it is important to obtain structures in the absence of a nanobody that may influence the structure. Here, we present a model for a rhodopsin-G protein complex derived from intermolecular distance constraints between the activated receptor and the inhibitory G protein, Gi, using electron paramagnetic resonance spectroscopy and spin-labeling methodologies. Molecular dynamics simulations demonstrated the overall stability of the modeled complex. In the rhodopsin-Gi complex, Gi engages rhodopsin in a manner distinct from previous GPCR-Gs structures, providing insight into specificity determinants.}, } @article {pmid29463719, year = {2018}, author = {Vlijm, R and Li, X and Panic, M and Rüthnick, D and Hata, S and Herrmannsdörfer, F and Kuner, T and Heilemann, M and Engelhardt, J and Hell, SW and Schiebel, E}, title = {STED nanoscopy of the centrosome linker reveals a CEP68-organized, periodic rootletin network anchored to a C-Nap1 ring at centrioles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2246-E2253}, pmid = {29463719}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Centrioles/chemistry/genetics/*metabolism ; Centrosome/chemistry/*metabolism ; Cytoskeletal Proteins/chemistry/genetics/*metabolism ; HeLa Cells ; Humans ; Interphase ; Microscopy ; Microtubule-Associated Proteins/chemistry/genetics/*metabolism ; Protein Binding ; Proteins/chemistry/genetics/*metabolism ; }, abstract = {The centrosome linker proteins C-Nap1, rootletin, and CEP68 connect the two centrosomes of a cell during interphase into one microtubule-organizing center. This coupling is important for cell migration, cilia formation, and timing of mitotic spindle formation. Very little is known about the structure of the centrosome linker. Here, we used stimulated emission depletion (STED) microscopy to show that each C-Nap1 ring at the proximal end of the two centrioles organizes a rootletin ring and, in addition, multiple rootletin/CEP68 fibers. Rootletin/CEP68 fibers originating from the two centrosomes form a web-like, interdigitating network, explaining the flexible nature of the centrosome linker. The rootletin/CEP68 filaments are repetitive and highly ordered. Staggered rootletin molecules (N-to-N and C-to-C) within the filaments are 75 nm apart. Rootletin binds CEP68 via its C-terminal spectrin repeat-containing region in 75-nm intervals. The N-to-C distance of two rootletin molecules is ∼35 to 40 nm, leading to an estimated minimal rootletin length of ∼110 nm. CEP68 is important in forming rootletin filaments that branch off centrioles and to modulate the thickness of rootletin fibers. Thus, the centrosome linker consists of a vast network of repeating rootletin units with C-Nap1 as ring organizer and CEP68 as filament modulator.}, } @article {pmid29463718, year = {2018}, author = {Duan, J and Li, Z and Li, J and Santa-Cruz, A and Sanchez-Martinez, S and Zhang, J and Clapham, DE}, title = {Structure of full-length human TRPM4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2377-2382}, pmid = {29463718}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cryoelectron Microscopy ; Humans ; Models, Molecular ; Sodium/chemistry/metabolism ; TRPM Cation Channels/*chemistry/genetics/*metabolism ; }, abstract = {Transient receptor potential melastatin subfamily member 4 (TRPM4) is a widely distributed, calcium-activated, monovalent-selective cation channel. Mutations in human TRPM4 (hTRPM4) result in progressive familial heart block. Here, we report the electron cryomicroscopy structure of hTRPM4 in a closed, Na+-bound, apo state at pH 7.5 to an overall resolution of 3.7 Å. Five partially hydrated sodium ions are proposed to occupy the center of the conduction pore and the entrance to the coiled-coil domain. We identify an upper gate in the selectivity filter and a lower gate at the entrance to the cytoplasmic coiled-coil domain. Intramolecular interactions exist between the TRP domain and the S4-S5 linker, N-terminal domain, and N and C termini. Finally, we identify aromatic interactions via π-π bonds and cation-π bonds, glycosylation at an N-linked extracellular site, a pore-loop disulfide bond, and 24 lipid binding sites. We compare and contrast this structure with other TRP channels and discuss potential mechanisms of regulation and gating of human full-length TRPM4.}, } @article {pmid29463717, year = {2018}, author = {Yuan, CC and Kazmierczak, K and Liang, J and Zhou, Z and Yadav, S and Gomes, AV and Irving, TC and Szczesna-Cordary, D}, title = {Sarcomeric perturbations of myosin motors lead to dilated cardiomyopathy in genetically modified MYL2 mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2338-E2347}, pmid = {29463717}, issn = {1091-6490}, support = {P41 GM103622/GM/NIGMS NIH HHS/United States ; R01 HL096819/HL/NHLBI NIH HHS/United States ; R01 HL123255/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Cardiomyopathy, Dilated/genetics/*metabolism/physiopathology ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Mice, Transgenic ; Mutation, Missense ; Myocardial Contraction ; Myocytes, Cardiac/metabolism ; Myosin Light Chains/genetics/*metabolism ; Sarcomeres/genetics/*metabolism ; }, abstract = {Dilated cardiomyopathy (DCM) is a devastating heart disease that affects about 1 million people in the United States, but the underlying mechanisms remain poorly understood. In this study, we aimed to determine the biomechanical and structural causes of DCM in transgenic mice carrying a novel mutation in the MYL2 gene, encoding the cardiac myosin regulatory light chain. Transgenic D94A (aspartic acid-to-alanine) mice were created and investigated by echocardiography and invasive hemodynamic and molecular structural and functional assessments. Consistent with the DCM phenotype, a significant reduction of the ejection fraction (EF) was observed in ∼5- and ∼12-mo-old male and female D94A lines compared with respective WT controls. Younger male D94A mice showed a more pronounced left ventricular (LV) chamber dilation compared with female counterparts, but both sexes of D94A lines developed DCM by 12 mo of age. The hypocontractile activity of D94A myosin motors resulted in the rightward shift of the force-pCa dependence and decreased actin-activated myosin ATPase activity. Consistent with a decreased Ca2+ sensitivity of contractile force, a small-angle X-ray diffraction study, performed in D94A fibers at submaximal Ca2+ concentrations, revealed repositioning of the D94A cross-bridge mass toward the thick-filament backbone supporting the hypocontractile state of D94A myosin motors. Our data suggest that structural perturbations at the level of sarcomeres result in aberrant cardiomyocyte cytoarchitecture and lead to LV chamber dilation and decreased EF, manifesting in systolic dysfunction of D94A hearts. The D94A-induced development of DCM in mice closely follows the clinical phenotype and suggests that MYL2 may serve as a new therapeutic target for dilated cardiomyopathy.}, } @article {pmid29463716, year = {2018}, author = {Morris, JL and Puttick, MN and Clark, JW and Edwards, D and Kenrick, P and Pressel, S and Wellman, CH and Yang, Z and Schneider, H and Donoghue, PCJ}, title = {The timescale of early land plant evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2274-E2283}, pmid = {29463716}, issn = {1091-6490}, support = {BB/N000919/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Biodiversity ; *Biological Evolution ; Ecosystem ; Fossils/history ; History, Ancient ; Phylogeny ; Plants/classification/*genetics ; Time Factors ; }, abstract = {Establishing the timescale of early land plant evolution is essential for testing hypotheses on the coevolution of land plants and Earth's System. The sparseness of early land plant megafossils and stratigraphic controls on their distribution make the fossil record an unreliable guide, leaving only the molecular clock. However, the application of molecular clock methodology is challenged by the current impasse in attempts to resolve the evolutionary relationships among the living bryophytes and tracheophytes. Here, we establish a timescale for early land plant evolution that integrates over topological uncertainty by exploring the impact of competing hypotheses on bryophyte-tracheophyte relationships, among other variables, on divergence time estimation. We codify 37 fossil calibrations for Viridiplantae following best practice. We apply these calibrations in a Bayesian relaxed molecular clock analysis of a phylogenomic dataset encompassing the diversity of Embryophyta and their relatives within Viridiplantae. Topology and dataset sizes have little impact on age estimates, with greater differences among alternative clock models and calibration strategies. For all analyses, a Cambrian origin of Embryophyta is recovered with highest probability. The estimated ages for crown tracheophytes range from Late Ordovician to late Silurian. This timescale implies an early establishment of terrestrial ecosystems by land plants that is in close accord with recent estimates for the origin of terrestrial animal lineages. Biogeochemical models that are constrained by the fossil record of early land plants, or attempt to explain their impact, must consider the implications of a much earlier, middle Cambrian-Early Ordovician, origin.}, } @article {pmid29463715, year = {2018}, author = {}, title = {Correction for Leftwich et al., Gut microbiomes and reproductive isolation in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2487}, doi = {10.1073/pnas.1801321115}, pmid = {29463715}, issn = {1091-6490}, } @article {pmid29463714, year = {2018}, author = {Correa-Costa, M and Gallo, D and Csizmadia, E and Gomperts, E and Lieberum, JL and Hauser, CJ and Ji, X and Wang, B and Câmara, NOS and Robson, SC and Otterbein, LE}, title = {Carbon monoxide protects the kidney through the central circadian clock and CD39.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2302-E2310}, pmid = {29463714}, issn = {1091-6490}, support = {R44 DK111260/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antigens, CD/genetics/*metabolism ; Apyrase/genetics/*metabolism ; Carbon Monoxide/*administration & dosage ; Disease Models, Animal ; Humans ; Kidney/blood supply/*drug effects/metabolism/physiopathology ; Kidney Diseases/*drug therapy/genetics/metabolism/physiopathology ; Male ; Mice ; Mice, Inbred C57BL ; Period Circadian Proteins/genetics/*metabolism ; Reperfusion Injury/genetics/metabolism/*prevention & control ; }, abstract = {Ischemia reperfusion injury (IRI) is the predominant tissue insult associated with organ transplantation. Treatment with carbon monoxide (CO) modulates the innate immune response associated with IRI and accelerates tissue recovery. The mechanism has been primarily descriptive and ascribed to the ability of CO to influence inflammation, cell death, and repair. In a model of bilateral kidney IRI in mice, we elucidate an intricate relationship between CO and purinergic signaling involving increased CD39 ectonucleotidase expression, decreased expression of Adora1, with concomitant increased expression of Adora2a/2b. This response is linked to a >20-fold increase in expression of the circadian rhythm protein Period 2 (Per2) and a fivefold increase in serum erythropoietin (EPO), both of which contribute to abrogation of kidney IRI. CO is ineffective against IRI in Cd39-/- and Per2-/- mice or in the presence of a neutralizing antibody to EPO. Collectively, these data elucidate a cellular signaling mechanism whereby CO modulates purinergic responses and circadian rhythm to protect against injury. Moreover, these effects involve CD39- and adenosinergic-dependent stabilization of Per2. As CO also increases serum EPO levels in human volunteers, these findings continue to support therapeutic use of CO to treat IRI in association with organ transplantation, stroke, and myocardial infarction.}, } @article {pmid29463713, year = {2018}, author = {Lee, J and Sutterlin, HA and Wzorek, JS and Mandler, MD and Hagan, CL and Grabowicz, M and Tomasek, D and May, MD and Hart, EM and Silhavy, TJ and Kahne, D}, title = {Substrate binding to BamD triggers a conformational change in BamA to control membrane insertion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2359-2364}, pmid = {29463713}, issn = {1091-6490}, support = {R35 GM118024/GM/NIGMS NIH HHS/United States ; R01 GM034821/GM/NIGMS NIH HHS/United States ; T32 GM007388/GM/NIGMS NIH HHS/United States ; F32 GM108258/GM/NIGMS NIH HHS/United States ; R01 AI081059/AI/NIAID NIH HHS/United States ; R37 GM034821/GM/NIGMS NIH HHS/United States ; F31 GM116210/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Outer Membrane Proteins/*chemistry/genetics/*metabolism ; Escherichia coli Proteins/*chemistry/genetics/*metabolism ; Kinetics ; Models, Molecular ; Periplasm/chemistry/metabolism ; Protein Binding ; Protein Conformation ; Protein Folding ; }, abstract = {The β-barrel assembly machine (Bam) complex folds and inserts integral membrane proteins into the outer membrane of Gram-negative bacteria. The two essential components of the complex, BamA and BamD, both interact with substrates, but how the two coordinate with each other during assembly is not clear. To elucidate aspects of this process we slowed the assembly of an essential β-barrel substrate of the Bam complex, LptD, by changing a conserved residue near the C terminus. This defective substrate is recruited to the Bam complex via BamD but is unable to integrate into the membrane efficiently. Changes in the extracellular loops of BamA partially restore assembly kinetics, implying that BamA fails to engage this defective substrate. We conclude that substrate binding to BamD activates BamA by regulating extracellular loop interactions for folding and membrane integration.}, } @article {pmid29463712, year = {2018}, author = {Weinreb, C and Wolock, S and Tusi, BK and Socolovsky, M and Klein, AM}, title = {Fundamental limits on dynamic inference from single-cell snapshots.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2467-E2476}, pmid = {29463712}, issn = {1091-6490}, support = {R01 DK100915/DK/NIDDK NIH HHS/United States ; T32 GM080177/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; *Gene Expression Profiling ; Hematopoiesis ; Hematopoietic Stem Cells/cytology/*metabolism ; Mice ; Single-Cell Analysis ; }, abstract = {Single-cell expression profiling reveals the molecular states of individual cells with unprecedented detail. Because these methods destroy cells in the process of analysis, they cannot measure how gene expression changes over time. However, some information on dynamics is present in the data: the continuum of molecular states in the population can reflect the trajectory of a typical cell. Many methods for extracting single-cell dynamics from population data have been proposed. However, all such attempts face a common limitation: for any measured distribution of cell states, there are multiple dynamics that could give rise to it, and by extension, multiple possibilities for underlying mechanisms of gene regulation. Here, we describe the aspects of gene expression dynamics that cannot be inferred from a static snapshot alone and identify assumptions necessary to constrain a unique solution for cell dynamics from static snapshots. We translate these constraints into a practical algorithmic approach, population balance analysis (PBA), which makes use of a method from spectral graph theory to solve a class of high-dimensional differential equations. We use simulations to show the strengths and limitations of PBA, and then apply it to single-cell profiles of hematopoietic progenitor cells (HPCs). Cell state predictions from this analysis agree with HPC fate assays reported in several papers over the past two decades. By highlighting the fundamental limits on dynamic inference faced by any method, our framework provides a rigorous basis for dynamic interpretation of a gene expression continuum and clarifies best experimental designs for trajectory reconstruction from static snapshot measurements.}, } @article {pmid29463711, year = {2018}, author = {Sheth, SN and Angert, AL}, title = {Demographic compensation does not rescue populations at a trailing range edge.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2413-2418}, pmid = {29463711}, issn = {1091-6490}, mesh = {California ; Climate Change ; Demography/*methods ; *Ecosystem ; Mimulus ; *Models, Biological ; *Models, Statistical ; *Population Dynamics ; }, abstract = {Species' geographic ranges and climatic niches are likely to be increasingly mismatched due to rapid climate change. If a species' range and niche are out of equilibrium, then population performance should decrease from high-latitude "leading" range edges, where populations are expanding into recently ameliorated habitats, to low-latitude "trailing" range edges, where populations are contracting from newly unsuitable areas. Demographic compensation is a phenomenon whereby declines in some vital rates are offset by increases in others across time or space. In theory, demographic compensation could increase the range of environments over which populations can succeed and forestall range contraction at trailing edges. An outstanding question is whether range limits and range contractions reflect inadequate demographic compensation across environmental gradients, causing population declines at range edges. We collected demographic data from 32 populations of the scarlet monkeyflower (Erythranthe cardinalis) spanning 11° of latitude in western North America and used integral projection models to evaluate population dynamics and assess demographic compensation across the species' range. During the 5-y study period, which included multiple years of severe drought and warming, population growth rates decreased from north to south, consistent with leading-trailing dynamics. Southern populations at the trailing range edge declined due to reduced survival, growth, and recruitment, despite compensatory increases in reproduction and faster life-history characteristics. These results suggest that demographic compensation may only delay population collapse without the return of more favorable conditions or the contribution of other buffering mechanisms such as evolutionary rescue.}, } @article {pmid29463710, year = {2018}, author = {Palmer, BA and Hirsch, A and Brumfeld, V and Aflalo, ED and Pinkas, I and Sagi, A and Rosenne, S and Oron, D and Leiserowitz, L and Kronik, L and Weiner, S and Addadi, L}, title = {Optically functional isoxanthopterin crystals in the mirrored eyes of decapod crustaceans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2299-2304}, pmid = {29463710}, issn = {1091-6490}, mesh = {Animals ; Crystallography, X-Ray ; Decapoda (Crustacea)/*physiology ; Nanoparticles/chemistry ; Photoreceptor Cells/*chemistry ; Retina/*chemistry/cytology ; Xanthopterin/*chemistry ; }, abstract = {The eyes of some aquatic animals form images through reflective optics. Shrimp, lobsters, crayfish, and prawns possess reflecting superposition compound eyes, composed of thousands of square-faceted eye units (ommatidia). Mirrors in the upper part of the eye (the distal mirror) reflect light collected from many ommatidia onto the photosensitive elements of the retina, the rhabdoms. A second reflector, the tapetum, underlying the retina, back-scatters dispersed light onto the rhabdoms. Using microCT and cryo-SEM imaging accompanied by in situ micro-X-ray diffraction and micro-Raman spectroscopy, we investigated the hierarchical organization and materials properties of the reflective systems at high resolution and under close-to-physiological conditions. We show that the distal mirror consists of three or four layers of plate-like nanocrystals. The tapetum is a diffuse reflector composed of hollow nanoparticles constructed from concentric lamellae of crystals. Isoxanthopterin, a pteridine analog of guanine, forms both the reflectors in the distal mirror and in the tapetum. The crystal structure of isoxanthopterin was determined from crystal-structure prediction calculations and verified by comparison with experimental X-ray diffraction. The extended hydrogen-bonded layers of the molecules result in an extremely high calculated refractive index in the H-bonded plane, n = 1.96, which makes isoxanthopterin crystals an ideal reflecting material. The crystal structure of isoxanthopterin, together with a detailed knowledge of the reflector superstructures, provide a rationalization of the reflective optics of the crustacean eye.}, } @article {pmid29463709, year = {2018}, author = {Wang, Y and Jin, J and Chung, MWH and Feng, L and Sun, H and Hao, Q}, title = {Identification of the YEATS domain of GAS41 as a pH-dependent reader of histone succinylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2365-2370}, pmid = {29463709}, issn = {1091-6490}, mesh = {Crystallography ; HeLa Cells ; Histidine/chemistry/metabolism ; Histone Acetyltransferases/chemistry/metabolism ; *Histones/chemistry/metabolism ; Humans ; Lysine/chemistry/metabolism ; Models, Molecular ; Protein Domains ; *Protein Processing, Post-Translational ; Saccharomyces cerevisiae Proteins/chemistry/metabolism ; *Succinic Acid/chemistry/metabolism ; *Transcription Factors/chemistry/metabolism ; }, abstract = {Lysine succinylation is a newly discovered posttranslational modification with distinctive physical properties. However, to date rarely have studies reported effectors capable of interpreting this modification on histones. Following our previous study of SIRT5 as an eraser of succinyl-lysine (Ksuc), here we identified the GAS41 YEATS domain as a reader of Ksuc on histones. Biochemical studies showed that the GAS41 YEATS domain presents significant binding affinity toward H3K122suc upon a protonated histidine residue. Furthermore, cellular studies showed that GAS41 had prominent interaction with H3K122suc on histones and also demonstrated the coenrichment of GAS41 and H3K122suc on the p21 promoter. To investigate the binding mechanism, we solved the crystal structure of the YEATS domain of Yaf9, the GAS41 homolog, in complex with an H3K122suc peptide that demonstrated the presence of a salt bridge formed when a protonated histidine residue (His39) recognizes the carboxyl terminal of the succinyl group. We also solved the apo structure of GAS41 YEATS domain, in which the conserved His43 residue superimposes well with His39 in the Yaf9 structure. Our findings identified a reader of succinyl-lysine, and the binding mechanism will provide insight into the development of specific regulators targeting GAS41.}, } @article {pmid29463708, year = {2018}, author = {Prado Lima, MG and Schimidt, HL and Garcia, A and Daré, LR and Carpes, FP and Izquierdo, I and Mello-Carpes, PB}, title = {Environmental enrichment and exercise are better than social enrichment to reduce memory deficits in amyloid beta neurotoxicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2403-E2409}, pmid = {29463708}, issn = {1091-6490}, mesh = {Alzheimer Disease/metabolism/psychology/*therapy ; Amyloid beta-Peptides/metabolism/*toxicity ; Animals ; Exercise ; *Exercise Therapy ; Hippocampus/metabolism ; Humans ; Lipid Peroxidation ; Male ; Maze Learning ; Memory ; Memory Disorders/metabolism/psychology/*therapy ; Oxidative Stress ; Rats ; Rats, Wistar ; Reactive Oxygen Species/metabolism ; Social Environment ; }, abstract = {Recently, nongenetic animal models to study the onset and development of Alzheimer's disease (AD) have appeared, such as the intrahippocampal infusion of peptides present in Alzheimer amyloid plaques [i.e., amyloid-β (Aβ)]. Nonpharmacological approaches to AD treatment also have been advanced recently, which involve combinations of behavioral interventions whose specific effects are often difficult to determine. Here we isolate the neuroprotective effects of three of these interventions-environmental enrichment (EE), anaerobic physical exercise (AnPE), and social enrichment (SE)-on Aβ-induced oxidative stress and on impairments in learning and memory induced by Aβ. Wistar rats were submitted to 8 wk of EE, AnPE, or SE, followed by Aβ infusion in the dorsal hippocampus. Short-term memory (STM) and long-term memory (LTM) of object recognition (OR) and social recognition (SR) were evaluated. Biochemical assays determined hippocampal oxidative status: reactive oxygen species, lipid peroxidation by thiobarbituric acid reactive substance (TBARS) test, and total antioxidant capacity by ferric reducing/antioxidant power (FRAP), as well as acetylcholinesterase activity. Aβ infusion resulted in memory deficits and hippocampal oxidative damage. EE and AnPE prevented all memory deficits (STM and LTM of OR and SR) and lipid peroxidation (i.e., TBARS). SE prevented only the SR memory deficits and the decrease of total antioxidant capacity decrease (i.e., FRAP). Traditionally, findings obtained with EE protocols do not allow discrimination of the roles of the three individual factors involved. Here we demonstrate that EE and physical exercise have better neuroprotective effects than SE in memory deficits related to Aβ neurotoxicity in the AD model tested.}, } @article {pmid29463707, year = {2018}, author = {Wang, J and Ding, M}, title = {Robo and Ror function in a common receptor complex to regulate Wnt-mediated neurite outgrowth in Caenorhabditis elegans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2254-E2263}, pmid = {29463707}, issn = {1091-6490}, mesh = {Animals ; Caenorhabditis elegans/chemistry/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Dishevelled Proteins/genetics/metabolism ; Nerve Tissue Proteins/chemistry/genetics/*metabolism ; Neurites/*metabolism ; Protein Binding ; Protein Domains ; Receptor Tyrosine Kinase-like Orphan Receptors/genetics/*metabolism ; Receptors, Immunologic/chemistry/genetics/*metabolism ; Signal Transduction ; Wnt Proteins/genetics/*metabolism ; }, abstract = {Growing axons are exposed to various guidance cues en route to their targets, but the mechanisms that govern the response of growth cones to combinations of signals remain largely elusive. Here, we found that the sole Robo receptor, SAX-3, in Caenorhabditis elegans functions as a coreceptor for Wnt/CWN-2 molecules. SAX-3 binds to Wnt/CWN-2 and facilitates the membrane recruitment of CWN-2. SAX-3 forms a complex with the Ror/CAM-1 receptor and its downstream effector Dsh/DSH-1, promoting signal transduction from Wnt to Dsh. sax-3 functions in Wnt-responsive cells and the SAX-3 receptor is restricted to the side of the cell from which the neurite is extended. DSH-1 has a similar asymmetric distribution, which is disrupted by sax-3 mutation. Taking these results together, we propose that Robo receptor can function as a Wnt coreceptor to regulate Wnt-mediated biological processes in vivo.}, } @article {pmid29463706, year = {2018}, author = {Fu, G and Bandaria, JN and Le Gall, AV and Fan, X and Yildiz, A and Mignot, T and Zusman, DR and Nan, B}, title = {MotAB-like machinery drives the movement of MreB filaments during bacterial gliding motility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2484-2489}, pmid = {29463706}, issn = {1091-6490}, support = {R01 GM020509/GM/NIGMS NIH HHS/United States ; R01 GM094522/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/chemistry/genetics/*metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Cell Movement/*physiology ; Luminescent Proteins/chemistry/genetics/metabolism ; Microscopy, Fluorescence ; Mutation ; Myxococcus xanthus/chemistry/genetics/*metabolism/*physiology ; Recombinant Fusion Proteins/chemistry/genetics/metabolism ; }, abstract = {MreB is a bacterial actin that is important for cell shape and cell wall biosynthesis in many bacterial species. MreB also plays crucial roles in Myxococcus xanthus gliding motility, but the underlying mechanism remains unknown. Here we tracked the dynamics of single MreB particles in M. xanthus using single-particle tracking photoactivated localization microscopy. We found that a subpopulation of MreB particles moves rapidly along helical trajectories, similar to the movements of the MotAB-like gliding motors. The rapid MreB motion was stalled in the mutants that carried truncated gliding motors. Remarkably, M. xanthus MreB moves one to two orders of magnitude faster than its homologs that move along with the cell wall synthesis machinery in Bacillus subtilis and Escherichia coli, and this rapid movement was not affected by the inhibitors of cell wall biosynthesis. Our results show that in M. xanthus, MreB provides a scaffold for the gliding motors while the gliding machinery drives the movement of MreB filaments, analogous to the interdependent movements of myosin motors and actin in eukaryotic cells.}, } @article {pmid29463705, year = {2018}, author = {Wang, YN and Figueiredo, D and Sun, XD and Dong, ZQ and Chen, WB and Cui, WP and Liu, F and Wang, HS and Li, HW and Robinson, H and Fei, EK and Pan, BX and Li, BM and Xiong, WC and Mei, L}, title = {Controlling of glutamate release by neuregulin3 via inhibiting the assembly of the SNARE complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2508-2513}, pmid = {29463705}, issn = {1091-6490}, support = {R01 AG051773/AG/NIA NIH HHS/United States ; R01 NS082007/NS/NINDS NIH HHS/United States ; R01 AG045781/AG/NIA NIH HHS/United States ; R01 NS090083/NS/NINDS NIH HHS/United States ; R21 MH109280/MH/NIMH NIH HHS/United States ; R01 MH083317/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Behavior, Animal/physiology ; Glutamic Acid/*metabolism ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Mental Disorders/genetics ; Mice ; Mice, Transgenic ; Pyramidal Cells/metabolism ; SNARE Proteins/*metabolism ; }, abstract = {Neuregulin3 (NRG3) is a growth factor of the neuregulin (NRG) family and a risk gene of various severe mental illnesses including schizophrenia, bipolar disorders, and major depression. However, the physiological function of NRG3 remains poorly understood. Here we show that loss of Nrg3 in GFAP-Nrg3f/f mice increased glutamatergic transmission, but had no effect on GABAergic transmission. These phenotypes were observed in Nex-Nrg3f/f mice, where Nrg3 was specifically knocked out in pyramidal neurons, indicating that Nrg3 regulates glutamatergic transmission by a cell-autonomous mechanism. Consequently, in the absence of Nrg3 in pyramidal neurons, mutant mice displayed various behavioral deficits related to mental illnesses. We show that the Nrg3 mutation decreased paired-pulse facilitation, increased decay of NMDAR currents when treated with MK801, and increased minimal stimulation-elicited response, providing evidence that the Nrg3 mutation increases glutamate release probability. Notably, Nrg3 is a presynaptic protein that regulates the SNARE-complex assembly. Finally, increased Nrg3 levels, as observed in patients with severe mental illnesses, suppressed glutamatergic transmission. Together, these observations indicate that, unlike the prototype Nrg1, the effect of which is mediated by activating ErbB4 in interneurons, Nrg3 is critical in controlling glutamatergic transmission by regulating the SNARE complex at the presynaptic terminals, identifying a function of Nrg3 and revealing a pathophysiological mechanism for hypofunction of the glutamatergic pathway in Nrg3-related severe mental illnesses.}, } @article {pmid29463704, year = {2018}, author = {}, title = {Correction for Goncalves et al., Fenofibrate prevents skeletal muscle loss in mice with lung cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2146}, doi = {10.1073/pnas.1801372115}, pmid = {29463704}, issn = {1091-6490}, } @article {pmid29463703, year = {2018}, author = {Zhou, J and Wei, J and Choy, KT and Sia, SF and Rowlands, DK and Yu, D and Wu, CY and Lindsley, WG and Cowling, BJ and McDevitt, J and Peiris, M and Li, Y and Yen, HL}, title = {Defining the sizes of airborne particles that mediate influenza transmission in ferrets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2386-E2392}, pmid = {29463703}, issn = {1091-6490}, support = {HHSN272201400006C/AI/NIAID NIH HHS/United States ; }, mesh = {Air/*analysis ; Air Microbiology ; Animals ; Ferrets ; Humans ; Influenza A Virus, H1N1 Subtype/chemistry/genetics/*physiology ; Influenza, Human/*transmission/*virology ; Male ; Virus Replication ; }, abstract = {Epidemics and pandemics of influenza are characterized by rapid global spread mediated by non-mutually exclusive transmission modes. The relative significance between contact, droplet, and airborne transmission is yet to be defined, a knowledge gap for implementing evidence-based infection control measures. We devised a transmission chamber that separates virus-laden particles by size and determined the particle sizes mediating transmission of influenza among ferrets through the air. Ferret-to-ferret transmission was mediated by airborne particles larger than 1.5 µm, consistent with the quantity and size of virus-laden particles released by the donors. Onward transmission by donors was most efficient before fever onset and may continue for 5 days after inoculation. Multiple virus gene segments enhanced the transmissibility of a swine influenza virus among ferrets by increasing the release of virus-laden particles into the air. We provide direct experimental evidence of influenza transmission via droplets and fine droplet nuclei, albeit at different efficiency.}, } @article {pmid29463702, year = {2018}, author = {Ghezzi, P and Davies, K and Delaney, A and Floridi, L}, title = {Theory of signs and statistical approach to big data in assessing the relevance of clinical biomarkers of inflammation and oxidative stress.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2473-2477}, pmid = {29463702}, issn = {1091-6490}, mesh = {Biomarkers/*analysis ; Computational Biology ; Databases, Factual ; Humans ; Inflammation/*diagnosis ; Models, Biological ; *Models, Statistical ; Oxidative Stress/*physiology ; Reactive Oxygen Species/analysis ; Reproducibility of Results ; }, abstract = {Biomarkers are widely used not only as prognostic or diagnostic indicators, or as surrogate markers of disease in clinical trials, but also to formulate theories of pathogenesis. We identify two problems in the use of biomarkers in mechanistic studies. The first problem arises in the case of multifactorial diseases, where different combinations of multiple causes result in patient heterogeneity. The second problem arises when a pathogenic mediator is difficult to measure. This is the case of the oxidative stress (OS) theory of disease, where the causal components are reactive oxygen species (ROS) that have very short half-lives. In this case, it is usual to measure the traces left by the reaction of ROS with biological molecules, rather than the ROS themselves. Borrowing from the philosophical theories of signs, we look at the different facets of biomarkers and discuss their different value and meaning in multifactorial diseases and system medicine to inform their use in patient stratification in personalized medicine.}, } @article {pmid29463701, year = {2018}, author = {Raynaud-Messina, B and Bracq, L and Dupont, M and Souriant, S and Usmani, SM and Proag, A and Pingris, K and Soldan, V and Thibault, C and Capilla, F and Al Saati, T and Gennero, I and Jurdic, P and Jolicoeur, P and Davignon, JL and Mempel, TR and Benichou, S and Maridonneau-Parini, I and Vérollet, C}, title = {Bone degradation machinery of osteoclasts: An HIV-1 target that contributes to bone loss.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2556-E2565}, pmid = {29463701}, issn = {1091-6490}, support = {R01 AI097052/AI/NIAID NIH HHS/United States ; R01 DA036298/DA/NIDA NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Actins/metabolism ; Animals ; Bone Resorption/*etiology/metabolism/pathology/physiopathology ; Bone and Bones/metabolism ; Cell Adhesion ; Female ; HIV Infections/*complications/metabolism/pathology/virology ; HIV-1/genetics/*physiology ; Humans ; Mice ; Osteoclasts/cytology/metabolism/*virology ; nef Gene Products, Human Immunodeficiency Virus/genetics/metabolism ; }, abstract = {Bone deficits are frequent in HIV-1-infected patients. We report here that osteoclasts, the cells specialized in bone resorption, are infected by HIV-1 in vivo in humanized mice and ex vivo in human joint biopsies. In vitro, infection of human osteoclasts occurs at different stages of osteoclastogenesis via cell-free viruses and, more efficiently, by transfer from infected T cells. HIV-1 infection markedly enhances adhesion and osteolytic activity of human osteoclasts by modifying the structure and function of the sealing zone, the osteoclast-specific bone degradation machinery. Indeed, the sealing zone is broader due to F-actin enrichment of its basal units (i.e., the podosomes). The viral protein Nef is involved in all HIV-1-induced effects partly through the activation of Src, a regulator of podosomes and of their assembly as a sealing zone. Supporting these results, Nef-transgenic mice exhibit an increased osteoclast density and bone defects, and osteoclasts derived from these animals display high osteolytic activity. Altogether, our study evidences osteoclasts as host cells for HIV-1 and their pathological contribution to bone disorders induced by this virus, in part via Nef.}, } @article {pmid29463700, year = {2018}, author = {}, title = {Correction for Conforti et al., Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2148}, doi = {10.1073/pnas.1801898115}, pmid = {29463700}, issn = {1091-6490}, } @article {pmid29463699, year = {2018}, author = {Serra, H and Lambing, C and Griffin, CH and Topp, SD and Nageswaran, DC and Underwood, CJ and Ziolkowski, PA and Séguéla-Arnaud, M and Fernandes, JB and Mercier, R and Henderson, IR}, title = {Massive crossover elevation via combination of HEI10 and recq4a recq4b during Arabidopsis meiosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2437-2442}, pmid = {29463699}, issn = {1091-6490}, support = {BB/K007882/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L006847/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/N007557/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M004937/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/*genetics ; Chromosomal Proteins, Non-Histone/*genetics ; Crossing Over, Genetic/*genetics ; DNA Helicases/*genetics ; DNA Methylation ; Homologous Recombination/*genetics ; Meiosis/*genetics ; }, abstract = {During meiosis, homologous chromosomes undergo reciprocal crossovers, which generate genetic diversity and underpin classical crop improvement. Meiotic recombination initiates from DNA double-strand breaks (DSBs), which are processed into single-stranded DNA that can invade a homologous chromosome. The resulting joint molecules can ultimately be resolved as crossovers. In Arabidopsis, competing pathways balance the repair of ∼100-200 meiotic DSBs into ∼10 crossovers per meiosis, with the excess DSBs repaired as noncrossovers. To bias DSB repair toward crossovers, we simultaneously increased dosage of the procrossover E3 ligase gene HEI10 and introduced mutations in the anticrossovers helicase genes RECQ4A and RECQ4B As HEI10 and recq4a recq4b increase interfering and noninterfering crossover pathways, respectively, they combine additively to yield a massive meiotic recombination increase. Interestingly, we also show that increased HEI10 dosage increases crossover coincidence, which indicates an effect on interference. We also show that patterns of interhomolog polymorphism and heterochromatin drive recombination increases distally towards the subtelomeres in both HEI10 and recq4a recq4b backgrounds, while the centromeres remain crossover suppressed. These results provide a genetic framework for engineering meiotic recombination landscapes in plant genomes.}, } @article {pmid29463698, year = {2018}, author = {Bernardo-Seisdedos, G and Nuñez, E and Gomis-Perez, C and Malo, C and Villarroel, Á and Millet, O}, title = {Structural basis and energy landscape for the Ca2+ gating and calmodulation of the Kv7.2 K+ channel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2395-2400}, pmid = {29463698}, issn = {1091-6490}, mesh = {Animals ; Calcium/chemistry/*metabolism ; Calmodulin/chemistry/*metabolism ; Cattle ; HEK293 Cells ; Humans ; *KCNQ2 Potassium Channel/chemistry/metabolism/physiology ; Protein Conformation ; Static Electricity ; Thermodynamics ; }, abstract = {The Kv7.2 (KCNQ2) channel is the principal molecular component of the slow voltage-gated, noninactivating K+ M-current, a key controller of neuronal excitability. To investigate the calmodulin (CaM)-mediated Ca2+ gating of the channel, we used NMR spectroscopy to structurally and dynamically describe the association of helices hA and hB of Kv7.2 with CaM, as a function of Ca2+ concentration. The structures of the CaM/Kv7.2-hAB complex at two different calcification states are reported here. In the presence of a basal cytosolic Ca2+ concentration (10-100 nM), only the N-lobe of CaM is Ca2+-loaded and the complex (representative of the open channel) exhibits collective dynamics on the millisecond time scale toward a low-populated excited state (1.5%) that corresponds to the inactive state of the channel. In response to a chemical or electrical signal, intracellular Ca2+ levels rise up to 1-10 μM, triggering Ca2+ association with the C-lobe. The associated conformational rearrangement is the key biological signal that shifts populations to the closed/inactive channel. This reorientation affects the C-lobe of CaM and both helices in Kv7.2, allosterically transducing the information from the Ca2+-binding site to the transmembrane region of the channel.}, } @article {pmid29463697, year = {2018}, author = {Ma, B and Zhou, Y and Chen, H and He, SJ and Huang, YH and Zhao, H and Lu, X and Zhang, WK and Pang, JH and Chen, SY and Zhang, JS}, title = {Membrane protein MHZ3 stabilizes OsEIN2 in rice by interacting with its Nramp-like domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2520-2525}, pmid = {29463697}, issn = {1091-6490}, mesh = {Ethylenes/metabolism ; Etiolation ; Membrane Proteins/chemistry/genetics/*metabolism ; Mutation ; Oryza/genetics/*metabolism ; Plant Growth Regulators/metabolism ; Plant Proteins/chemistry/genetics/*metabolism ; Plants, Genetically Modified/genetics/*metabolism ; Protein Domains ; Seedlings/genetics/metabolism ; Signal Transduction/genetics/physiology ; }, abstract = {The phytohormone ethylene regulates many aspects of plant growth and development. EIN2 is the central regulator of ethylene signaling, and its turnover is crucial for triggering ethylene responses. Here, we identified a stabilizer of OsEIN2 through analysis of the rice ethylene-response mutant mhz3. Loss-of-function mutations lead to ethylene insensitivity in etiolated rice seedlings. MHZ3 encodes a previously uncharacterized membrane protein localized to the endoplasmic reticulum. Ethylene induces MHZ3 gene and protein expression. Genetically, MHZ3 acts at the OsEIN2 level in the signaling pathway. MHZ3 physically interacts with OsEIN2, and both the N- and C-termini of MHZ3 specifically associate with the OsEIN2 Nramp-like domain. Loss of mhz3 function reduces OsEIN2 abundance and attenuates ethylene-induced OsEIN2 accumulation, whereas MHZ3 overexpression elevates the abundance of both wild-type and mutated OsEIN2 proteins, suggesting that MHZ3 is required for proper accumulation of OsEIN2 protein. The association of MHZ3 with the Nramp-like domain is crucial for OsEIN2 accumulation, demonstrating the significance of the OsEIN2 transmembrane domains in ethylene signaling. Moreover, MHZ3 negatively modulates OsEIN2 ubiquitination, protecting OsEIN2 from proteasome-mediated degradation. Together, these results suggest that ethylene-induced MHZ3 stabilizes OsEIN2 likely by binding to its Nramp-like domain and impeding protein ubiquitination to facilitate ethylene signal transduction. Our findings provide insight into the mechanisms of ethylene signaling.}, } @article {pmid29463696, year = {2018}, author = {Zhang, H and Li, HS and Hillmer, EJ and Zhao, Y and Chrisikos, TT and Hu, H and Wu, X and Thompson, EJ and Clise-Dwyer, K and Millerchip, KA and Wei, Y and Puebla-Osorio, N and Kaushik, S and Santos, MA and Wang, B and Garcia-Manero, G and Wang, J and Sun, SC and Watowich, SS}, title = {Genetic rescue of lineage-balanced blood cell production reveals a crucial role for STAT3 antiinflammatory activity in hematopoiesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2311-E2319}, pmid = {29463696}, issn = {1091-6490}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 AI057555/AI/NIAID NIH HHS/United States ; R01 AI109294/AI/NIAID NIH HHS/United States ; R01 CA155025/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Blood Cells/cytology/*immunology ; Cell Lineage ; Female ; *Hematopoiesis ; Hematopoietic Stem Cells/cytology/immunology ; Male ; Mice ; Mice, Inbred C57BL ; Myeloid Cells/cytology/immunology ; STAT3 Transcription Factor/genetics/*immunology ; Ubiquitin-Conjugating Enzymes/genetics/immunology ; }, abstract = {Blood cell formation must be appropriately maintained throughout life to provide robust immune function, hemostasis, and oxygen delivery to tissues, and to prevent disorders that result from over- or underproduction of critical lineages. Persistent inflammation deregulates hematopoiesis by damaging hematopoietic stem and progenitor cells (HSPCs), leading to elevated myeloid cell output and eventual bone marrow failure. Nonetheless, antiinflammatory mechanisms that protect the hematopoietic system are understudied. The transcriptional regulator STAT3 has myriad roles in HSPC-derived populations and nonhematopoietic tissues, including a potent antiinflammatory function in differentiated myeloid cells. STAT3 antiinflammatory activity is facilitated by STAT3-mediated transcriptional repression of Ube2n, which encodes the E2 ubiquitin-conjugating enzyme Ubc13 involved in proinflammatory signaling. Here we demonstrate a crucial role for STAT3 antiinflammatory activity in preservation of HSPCs and lineage-balanced hematopoiesis. Conditional Stat3 removal from the hematopoietic system led to depletion of the bone marrow lineage- Sca-1+ c-Kit+ CD150+ CD48- HSPC subset (LSK CD150+ CD48- cells), myeloid-skewed hematopoiesis, and accrual of DNA damage in HSPCs. These responses were accompanied by intrinsic transcriptional alterations in HSPCs, including deregulation of inflammatory, survival and developmental pathways. Concomitant Ube2n/Ubc13 deletion from Stat3-deficient hematopoietic cells enabled lineage-balanced hematopoiesis, mitigated depletion of bone marrow LSK CD150+ CD48- cells, alleviated HSPC DNA damage, and corrected a majority of aberrant transcriptional responses. These results indicate an intrinsic protective role for STAT3 in the hematopoietic system, and suggest that this is mediated by STAT3-dependent restraint of excessive proinflammatory signaling via Ubc13 modulation.}, } @article {pmid29463695, year = {2018}, author = {Ryan, SF and Deines, JM and Scriber, JM and Pfrender, ME and Jones, SE and Emrich, SJ and Hellmann, JJ}, title = {Climate-mediated hybrid zone movement revealed with genomics, museum collection, and simulation modeling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2284-E2291}, pmid = {29463695}, issn = {1091-6490}, mesh = {Animals ; Breeding ; Butterflies/*genetics/physiology ; *Climate Change ; *Ecosystem ; Female ; Genetic Variation ; Genomics ; Geography ; Hybridization, Genetic ; Male ; Models, Biological ; Museums/statistics & numerical data ; }, abstract = {Climate-mediated changes in hybridization will dramatically alter the genetic diversity, adaptive capacity, and evolutionary trajectory of interbreeding species. Our ability to predict the consequences of such changes will be key to future conservation and management decisions. Here we tested through simulations how recent warming (over the course of a 32-y period) is affecting the geographic extent of a climate-mediated developmental threshold implicated in maintaining a butterfly hybrid zone (Papilio glaucus and Papilio canadensis; Lepidoptera: Papilionidae). These simulations predict a 68-km shift of this hybrid zone. To empirically test this prediction, we assessed genetic and phenotypic changes using contemporary and museum collections and document a 40-km northward shift of this hybrid zone. Interactions between the two species appear relatively unchanged during hybrid zone movement. We found no change in the frequency of hybridization, and regions of the genome that experience little to no introgression moved largely in concert with the shifting hybrid zone. Model predictions based on climate scenarios predict this hybrid zone will continue to move northward, but with substantial spatial heterogeneity in the velocity (55-144 km/1 °C), shape, and contiguity of movement. Our findings suggest that the presence of nonclimatic barriers (e.g., genetic incompatibilities) and/or nonlinear responses to climatic gradients may preserve species boundaries as the species shift. Further, we show that variation in the geography of hybrid zone movement could result in evolutionary responses that differ for geographically distinct populations spanning hybrid zones, and thus have implications for the conservation and management of genetic diversity.}, } @article {pmid29463694, year = {2018}, author = {van der Vinne, V and Swoap, SJ and Vajtay, TJ and Weaver, DR}, title = {Desynchrony between brain and peripheral clocks caused by CK1δ/ε disruption in GABA neurons does not lead to adverse metabolic outcomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2437-E2446}, pmid = {29463694}, issn = {1091-6490}, support = {R01 NS056125/NS/NINDS NIH HHS/United States ; R15 HL120072/HL/NHLBI NIH HHS/United States ; R21 ES024684/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Casein Kinase Idelta/deficiency/*genetics ; Casein Kinase Iepsilon/deficiency/*genetics ; *Circadian Clocks ; Circadian Rhythm ; Female ; GABAergic Neurons/*enzymology ; Gene Knockout Techniques ; Gene Silencing ; Male ; Mice ; Mice, Inbred C57BL ; Suprachiasmatic Nucleus/enzymology/*physiology ; }, abstract = {Circadian disruption as a result of shift work is associated with adverse metabolic consequences. Internal desynchrony between the phase of the suprachiasmatic nuclei (SCN) and peripheral clocks is widely believed to be a major factor contributing to these adverse consequences, but this hypothesis has never been tested directly. A GABAergic Cre driver combined with conditional casein kinase mutations (Vgat-Cre+ CK1δfl/fl εfl/+) was used to lengthen the endogenous circadian period in GABAergic neurons, including the SCN, but not in peripheral tissues, to create a Discordant mouse model. These mice had a long (27.4 h) behavioral period to which peripheral clocks entrained in vivo, albeit with an advanced phase (∼6 h). Thus, in the absence of environmental timing cues, these mice had internal desynchrony between the SCN and peripheral clocks. Surprisingly, internal desynchrony did not result in obesity in this model. Instead, Discordant mice had reduced body mass compared with Cre-negative controls on regular chow and even when challenged with a high-fat diet. Similarly, internal desynchrony failed to induce glucose intolerance or disrupt body temperature and energy expenditure rhythms. Subsequently, a lighting cycle of 2-h light/23.5-h dark was used to create a similar internal desynchrony state in both genotypes. Under these conditions, Discordant mice maintained their lower body mass relative to controls, suggesting that internal desynchrony did not cause the lowered body mass. Overall, our results indicate that internal desynchrony does not necessarily lead to metabolic derangements and suggest that additional mechanisms contribute to the adverse metabolic consequences observed in circadian disruption protocols.}, } @article {pmid29463317, year = {2018}, author = {Suzuki, K and Shimada, Y and Seno, Y and Mizuguchi, T and Tanikawa, A and Horiguchi, M}, title = {Adherence to the face-down positioning after vitrectomy and gas tamponade: a time series analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {142}, pmid = {29463317}, issn = {1756-0500}, mesh = {Aged ; Female ; Humans ; Male ; Middle Aged ; Patient Compliance/*statistics & numerical data ; Postoperative Period ; *Prone Position ; Retinal Detachment/*surgery ; Retinal Perforations/*surgery ; Retrospective Studies ; Sex Factors ; Time Factors ; Vitrectomy/*statistics & numerical data ; }, abstract = {OBJECTIVE: To determine the adherence to the face-down positioning (FDP) in 296 patients who had undergone vitrectomy and gas tamponade.

RESULTS: We studied 119 female and 177 male patients who had undergone primary vitrectomy and gas tamponade for a macular hole (MH) or for rhegmatogenous retinal detachments (RRDs). Adherence was assessed and recorded four times per day for 3 days postsurgery. The mean ± standard deviation adherence rate was 88.3 ± 11.7 (range 50.0-100.0). Female patients (90.8 ± 10.0) had significantly better adherence than male patients (86.7 ± 13.3; P < 0.02, U test). The adherence was significantly better after MH surgery (90.8 ± 11.7) than after RRD surgery (87.5 ± 12.5; P < 0.02). There were diurnal variations in adherence, being highest in the evening and significantly lower at midnight, and we evidenced a decline in adherence over time, with it being significantly low on the last follow-up day. Adherence to the FDP varied considerably among patients. Adherence was higher in female than in male patients, and higher in patients with MH than in those with RRD. We found patients age had no effect on adherence. Adherence also varied with time, being worst at midnight and declining over time.}, } @article {pmid29463316, year = {2018}, author = {Fuchshuber, J and Hiebler-Ragger, M and Ragger, K and Rinner, A and Kapfhammer, HP and Unterrainer, HF}, title = {Increased attachment security is related to early therapy drop-out in substance use disorders.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {141}, pmid = {29463316}, issn = {1756-0500}, mesh = {Adult ; Cluster Analysis ; Community Mental Health Services ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; *Object Attachment ; Patient Compliance/*psychology ; Patient Dropouts/*psychology ; Substance-Related Disorders/*psychology/*therapy ; }, abstract = {OBJECTIVES: Previous research work suggests a positive association between secure attachment and increased therapy adherence (TA) in different patient groups. However, there is still a strong need for research focusing on the influence of attachment on TA in substance use disorder (SUD) treatment. Hence, this study attempts to investigate the predictive value of different attachment patterns concerning TA in SUD inpatients.

RESULTS: 122 (34 female) SUD inpatients completed the Attachment Style Questionnaire (ASQ) during the entry phase of therapeutic community treatment. After 6 weeks, subjects who remained in therapy (n = 47) completed the ASQ for a second time. In line with the literature, agglomerative Cluster Analysis suggested a two-cluster solution (Cluster I: increased secure attachment pattern; Cluster II: increased insecure attachment pattern). Notably, inpatients in Cluster I were more likely to drop out of treatment within the first 6 weeks (p < .001). Furthermore, subjects showed less "Confidence in Self and Others" (p < .05) after 6 weeks of treatment. Our findings indicate a negative predictive value of increased attachment security for TA in SUD inpatients. This finding probably mirrors a more realistic kind of self-assessment. More generally, the importance of considering attachment styles in SUD treatment is underlined.}, } @article {pmid29463306, year = {2018}, author = {Tremblay, CS and Huang, FF and Lévesque, G and Carreau, M}, title = {Fanconi anemia core complex-dependent HES1 mono-ubiquitination regulates its transcriptional activity.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {138}, pmid = {29463306}, issn = {1756-0500}, mesh = {Cell Line ; Fanconi Anemia/*metabolism ; Fanconi Anemia Complementation Group Proteins/*metabolism ; Fibroblasts ; HEK293 Cells ; HeLa Cells ; Humans ; Multiprotein Complexes/*metabolism ; Transcription Factor HES-1/*metabolism ; *Ubiquitination ; }, abstract = {OBJECTIVE: The Hairy Enhancer of Split 1 (HES1) is a transcriptional repressor that regulates cellular proliferation and differentiation during development. We previously found an interaction between HES1 and Fanconi anemia (FA) proteins. FA is a hematological and developmental disorder caused by mutations in more than 20 different genes. Eight FA gene products form a nuclear core complex containing E3 ligase activity required for mono-ubiquitination of FANCD2 and FANCI, both of which are FA proteins. Given that HES1 interacts with members of the FA core complex, the aim of this study was to determine whether HES1 is mono-ubiquitinated via the FA core complex.

RESULTS: We show that HES1 is mono-ubiquitinated on a highly-conserved lysine residue that is located within a FA-like recognition motif. HES1 modification is dependent on a functional FA complex. Absence of HES1 mono-ubiquitination affects transcriptional repression of its own promoter. This study uncovers a novel post-translational modification of HES1 that regulates its transcriptional activity and suggests that ubiquitination of HES1 occurs in a FA core complex-dependent manner.}, } @article {pmid29463304, year = {2018}, author = {Teklemariam, D and Legesse, M and Degarege, A and Liang, S and Erko, B}, title = {Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys in Lake Ziway area, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {146}, pmid = {29463304}, issn = {1756-0500}, support = {R01 AI125842/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cercopithecus aethiops/*parasitology ; Child ; Ethiopia/epidemiology ; Female ; Humans ; Intestinal Diseases, Parasitic/*epidemiology/transmission/veterinary ; Male ; Schistosomiasis mansoni/*epidemiology/transmission/veterinary ; Zoonoses/*epidemiology/transmission ; }, abstract = {OBJECTIVE: To assess Schistosoma mansoni and other intestinal parasitic infections in schoolchildren and vervet monkeys (Chlorocebus aethiops) in Bochessa Village, Ziway, Ethiopia.

RESULTS: Fecal specimens from selected schoolchildren and droppings of the vervet monkeys were collected and microscopically examined for intestinal parasites using the Kato-Katz thick smear and formol-ether concentration techniques. The prevalences of S. mansoni, Trichuris trichiura, Ascaris lumbricoides, Enterobius vermicularis, hookworms, Hymenolepis nana and Taenia species among the children were 35.7, 26.9, 24.1, 2.1, 2.1, 1.07 and 2.1%, respectively (by Kato-Katz) and 39.3, 36.1, 35.6, 2.9, 10.0, 4.3, and 2.9%, respectively (by formol-ether concentration). Prevalence of S. mansoni in vervet monkeys ranged from 10 to 20%. B. pfeifferi snails were exposed to S. mansoni miracidia from vervet origin, shed cercariae were then used to infect lab-bred albino mice. Adult worms were harvested from the mice 5 weeks post-exposure to cercariae to establish the schistosome life cycle and confirm the infection in the vervet monkeys. The natural infection of S. mansoni in vervet monkeys suggests that the non-human primate is likely to be implicated in the local transmission of schistosomiasis. Further epidemiological and molecular studies are needed to fully elucidate zoonotic role of non-human primate in the area.}, } @article {pmid29463303, year = {2018}, author = {Costanzi, JM and Bergan, F and Sæbø, M and Jenkins, A and Steifetten, Ø}, title = {Development and evaluation of 16 new microsatellite loci for the rock ptarmigan (Lagopus muta) and cross-species amplification for the willow grouse (L. lagopus).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {147}, pmid = {29463303}, issn = {1756-0500}, mesh = {Animals ; Galliformes/*genetics ; Genetic Loci ; Genetics, Population/*methods ; High-Throughput Nucleotide Sequencing ; Microsatellite Repeats/*genetics ; Norway ; Sweden ; }, abstract = {OBJECTIVE: The genetic markers designed for this study can facilitate future genetic studies on the rock ptarmigan (Lagopus muta). To our knowledge no microsatellite markers have ever been developed specifically for this species before. These new microsatellite markers will be useful for population genetics studies and for future conservation projects.

RESULTS: Using Next Generation Sequencing 6252 potential microsatellite sequences were found. Sixteen nonpalindromic tetranucleotide microsatellites and their respective primers were selected. The markers were tested on both the rock ptarmigan and the willow grouse (L. lagopus). The number of alleles varied between 2 and 18 for the rock ptarmigan, and between 3 and 13 for the willow grouse. Expected heterozygosity was in the range 0.1244-0.8692 and 0.1358-0.8722 for the rock ptarmigan and the willow grouse, respectively.}, } @article {pmid29463301, year = {2018}, author = {Zhang, J and Chen, L and Wang, J and Butaye, P and Huang, K and Qiu, H and Zhang, X and Gong, W and Wang, C}, title = {Molecular detection of colistin resistance genes (mcr-1 to mcr-5) in human vaginal swabs.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {143}, pmid = {29463301}, issn = {1756-0500}, support = {31472225//National Natural Science Foundation of China/ ; }, mesh = {Adult ; Anti-Bacterial Agents/*pharmacology ; Colistin/*pharmacology ; Drug Resistance, Bacterial/*genetics ; Female ; Genes, Bacterial/*genetics ; Humans ; R Factors/*genetics ; Vagina/*microbiology ; }, abstract = {OBJECTIVE: Colistin resistance has emerged worldwide and has been threatening the efficacy of one of the last-resort antimicrobials used for treatment of multidrug resistant Gram-negative bacteria. While five colistin resistance genes (mcr-1, mcr-2, mcr-3, mcr-4 and mcr-5) have been described, few data are available on the prevalence of mcr-genes other than mcr-1 in human samples.

RESULTS: In this study, the presence of five currently described colistin resistance genes (mcr 1-5) in vaginal swabs of women undergoing infertility evaluation was reported. Most samples were found to be positive for the mcr-4 (12.7%), followed by two for the mcr-2 (1.5%), two for the mcr-3 (1.5%), one for the mcr-1 (0.7%), and one for the mcr-5 (0.7%). Phylogenetic comparison demonstrated identical (mcr-1, mcr-2, mcr-3, mcr-5) or similar (mcr-4) nucleotide sequences of human samples and those of animal origins from the same city, suggesting the potential transmission of mcr genes from animals to humans. This is the first detection of mcr-2, mcr-4 and mcr-5 genes in human samples, and warrants further research to determine the spread of the mcr genes and elucidate the full epidemiology of colistin resistance genes in humans.}, } @article {pmid29463299, year = {2018}, author = {Kassa, RT}, title = {Risk factors associated with precancerous cervical lesion among women screened at Marie Stops Ethiopia, Adama town, Ethiopia 2017: a case control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {145}, pmid = {29463299}, issn = {1756-0500}, mesh = {Adult ; Case-Control Studies ; *Early Detection of Cancer ; Ethiopia/epidemiology ; Female ; Humans ; Middle Aged ; Risk Factors ; Sexually Transmitted Diseases/*complications/epidemiology ; Uterine Cervical Neoplasms/*diagnosis/epidemiology/etiology/*pathology ; }, abstract = {OBJECTIVE: Although cervical cancer is a preventable disease, it remains a leading cause of death among women in developing countries. In this unmatched case control design, 55 cases and 109 controls were included. The main objective of this study was to assess the risk factors of precancerous cervical lesion in Adama town.

RESULTS: A total of 164 participants were recruited in this study. Of the 109 controls, 64 (61%) and 41 (39%) of cases were using oral contraception. Women who were using oral contraception were two times at risk for developing precancerous cervical lesion than who were not using (COR = 2.059 95% CI 1.006, 4.216; AOR = 2.342). Out of 55 cases, 21 (38.2%) cases had a history STI and out of 109 controls, 24 (22.2%) controls had a history of STI. It was revealed that STI has a significant association for developing of precancerous lesion. Women who had a history of STI were two times at risk of developing precancerous cervical lesion than who had no (COR = 2.187; AOR = 2.485). It was found that initiation of sexual intercourse before the age of 15 years has 5.6 risks to develop precancerous cervical lesion (COR = 5.625 AOR = 6.703).}, } @article {pmid29463295, year = {2018}, author = {Brener-Raffalli, K and Clerissi, C and Vidal-Dupiol, J and Adjeroud, M and Bonhomme, F and Pratlong, M and Aurelle, D and Mitta, G and Toulza, E}, title = {Thermal regime and host clade, rather than geography, drive Symbiodinium and bacterial assemblages in the scleractinian coral Pocillopora damicornis sensu lato.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {39}, pmid = {29463295}, issn = {2049-2618}, support = {ANR-12-ADAP-0016//Agence Nationale de la Recherche/International ; }, mesh = {Acinetobacter/genetics/*isolation & purification ; Animals ; Anthozoa/*microbiology/*parasitology ; Arcobacter/genetics/*isolation & purification ; DNA, Intergenic/genetics ; Dinoflagellida/genetics/*isolation & purification ; High-Throughput Nucleotide Sequencing ; Microbiota/genetics ; Oceanospirillaceae/genetics/*isolation & purification ; RNA, Ribosomal, 16S/genetics ; Symbiosis/physiology ; }, abstract = {BACKGROUND: Although the term holobiont has been popularized in corals with the advent of the hologenome theory of evolution, the underlying concepts are still a matter of debate. Indeed, the relative contribution of host and environment and especially thermal regime in shaping the microbial communities should be examined carefully to evaluate the potential role of symbionts for holobiont adaptation in the context of global changes. We used the sessile, long-lived, symbiotic and environmentally sensitive reef-building coral Pocillopora damicornis to address these issues.

RESULTS: We sampled Pocillopora damicornis colonies corresponding to two different mitochondrial lineages in different geographic areas displaying different thermal regimes: Djibouti, French Polynesia, New Caledonia, and Taiwan. The community composition of bacteria and the algal endosymbiont Symbiodinium were characterized using high-throughput sequencing of 16S rRNA gene and internal transcribed spacer, ITS2, respectively. Bacterial microbiota was very diverse with high prevalence of Endozoicomonas, Arcobacter, and Acinetobacter in all samples. While Symbiodinium sub-clade C1 was dominant in Taiwan and New Caledonia, D1 was dominant in Djibouti and French Polynesia. Moreover, we also identified a high background diversity (i.e., with proportions < 1%) of A1, C3, C15, and G Symbiodinum sub-clades. Using redundancy analyses, we found that the effect of geography was very low for both communities and that host genotypes and temperatures differently influenced Symbiodinium and bacterial microbiota. Indeed, while the constraint of host haplotype was higher than temperatures on bacterial composition, we showed for the first time a strong relationship between the composition of Symbiodinium communities and minimal sea surface temperatures.

CONCLUSION: Because Symbiodinium assemblages are more constrained by the thermal regime than bacterial communities, we propose that their contribution to adaptive capacities of the holobiont to temperature changes might be higher than the influence of bacterial microbiota. Moreover, the link between Symbiodinium community composition and minimal temperatures suggests low relative fitness of clade D at lower temperatures. This observation is particularly relevant in the context of climate change, since corals will face increasing temperatures as well as much frequent abnormal cold episodes in some areas of the world.}, } @article {pmid29463293, year = {2018}, author = {Seid, A and Tamir, Z and Kasanew, B and Senbetay, M}, title = {Co-infection of intestinal parasites and Helicobacter pylori among upper gastrointestinal symptomatic adult patients attending Mekanesalem Hospital, northeast Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {144}, pmid = {29463293}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; *Coinfection ; Comorbidity ; Drinking Water/*microbiology/parasitology ; Ethiopia/epidemiology ; Female ; *Giardia lamblia/isolation & purification/pathogenicity ; Giardiasis/epidemiology/parasitology ; Helicobacter Infections/*epidemiology/microbiology ; *Helicobacter pylori/isolation & purification/pathogenicity ; Humans ; Intestinal Diseases, Parasitic/*epidemiology/parasitology ; Male ; Middle Aged ; Sex Factors ; Young Adult ; }, abstract = {OBJECTIVE: Intestinal parasites and H. pylori are well-known for their high prevalence worldwide. Thus, the objective of this study waste assess risk factors and co-infection of intestinal parasites and H. pylori among adult patients with upper gastrointestinal complaints. A hospital-based cross sectional study was conducted among 363 consecutive adult patients from December 10, 2015 to February 30,2016. Stool and venous blood were collected for analysis of Intestinal parasites and H. pylori infection, respectively. Data was analyzed using SPSS version 16 and logistic regression analysis was carried out to assess predictors of co-infection. A p ≤ 0.05 was considered as statistically significant.

RESULTS: Helicobacter pylori IgG and intestinal parasites were detected in 70.25-38.3% of participants, respectively while G. lamblia accounted 22.3%. G. lamblia prevalence was significantly higher among H. pylori infected participants (COR: 2.76; 95% CI: 1.46-5.23), but E. hystolytica/dispar infection didn't show significant variation (p = 0.15). H. pylori and intestinal parasites concomitant co-infection was associated with male sex (AOR: 1.61; 95% CI: 1.01-2.56), consumption of river water (AOR: 1.85; 95% CI: 1.11-3.07) and ground/spring water (AOR: 4.10; 95% CI: 1.97-8.52). Thus, besides H. pylori investigation, upper gastrointestinal symptomatic patients should be screened for G. lamblia infection and other intestinal parasites.}, } @article {pmid29463247, year = {2018}, author = {Qi, X and Torii, KU}, title = {Hormonal and environmental signals guiding stomatal development.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {21}, pmid = {29463247}, issn = {1741-7007}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Stomata are pores on plant epidermis that facilitate gas exchange and water evaporation between plants and the environment. Given the central role of stomata in photosynthesis and water-use efficiency, two vital events for plant growth, stomatal development is tightly controlled by a diverse range of signals. A family of peptide hormones regulates stomatal patterning and differentiation. In addition, plant hormones as well as numerous environmental cues influence the decision of whether to make stomata or not in distinct and complex manners. In this review, we summarize recent findings that reveal the mechanism of these three groups of signals in controlling stomatal formation, and discuss how these signals are integrated into the core stomatal development pathway.}, } @article {pmid29463232, year = {2018}, author = {Orenstein, Y and Ohler, U and Berger, B}, title = {Finding RNA structure in the unstructured RBPome.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {154}, pmid = {29463232}, issn = {1471-2164}, support = {R01 GM081871/GM/NIGMS NIH HHS/United States ; R01GM081871/NH/NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Binding Sites ; Models, Theoretical ; *Nucleic Acid Conformation ; Nucleotide Motifs ; Protein Binding ; RNA/*chemistry/genetics ; RNA-Binding Proteins/*chemistry/genetics/metabolism ; Reproducibility of Results ; Structure-Activity Relationship ; }, abstract = {BACKGROUND: RNA-binding proteins (RBPs) play vital roles in many processes in the cell. Different RBPs bind RNA with different sequence and structure specificities. While sequence specificities for a large set of 205 RBPs have been reported through the RNAcompete compendium, structure specificities are known for only a small fraction. The main limitation lies in the design of the RNAcompete technology, which tests RBP binding against unstructured RNA probes, making it difficult to infer structural preferences from these data. We recently developed RCK, an algorithm to infer sequence and structural binding models from RNAcompete data. The set of binding models enables, for the first time, a large-scale assessment of RNA structure in the RBPome.

RESULTS: We re-validate and uncover the role of RNA structure in the RPBome through novel analysis of the largest-scale dataset to date. First, we show that RNA structure exists in presumably unstructured RNA probes and that its variability is correlated with RNA-binding. Second, we examine the structural binding preferences of RBPs and discover an overall preference to bind RNA loops. Third, we significantly improve protein-binding prediction using RNA structure, both in vitro and in vivo. Lastly, we demonstrate that RNA structural binding preferences can be inferred for new proteins from solely their amino acid content.

CONCLUSIONS: By counter-intuitively demonstrating through our analysis that we can predict both the RNA structure of and RBP binding to these putatively unstructured RNAs, we transform a compendium of RNA-binding proteins into a valuable resource for structure-based binding models. We uncover the important role RNA structure plays in protein-RNA interaction for hundreds of RNA-binding proteins.}, } @article {pmid29463217, year = {2018}, author = {Welker, F}, title = {Elucidation of cross-species proteomic effects in human and hominin bone proteome identification through a bioinformatics experiment.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {23}, pmid = {29463217}, issn = {1471-2148}, support = {17649//Villum Fonden/International ; }, mesh = {Algorithms ; Amino Acid Sequence ; Amino Acids/genetics ; Animals ; Computational Biology/*methods ; Hominidae/*metabolism ; Humans ; Mutation/genetics ; Peptides/metabolism ; Phylogeny ; Proteome/*metabolism ; Proteomics/*methods ; }, abstract = {BACKGROUND: The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein identifications at increased evolutionary distances due to a larger number of protein sequence differences between the database sequence and the analyzed organism. Error-tolerant proteomic search algorithms should theoretically overcome this problem at both the peptide and protein level; however, this has not been demonstrated. If error-tolerant searches do not overcome the cross-species proteomic issue then there might be inherent biases in the identified proteomes. Here, a bioinformatics experiment is performed to test this using a set of modern human bone proteomes and three independent searches against sequence databases at increasing evolutionary distances: the human (0 Ma), chimpanzee (6-8 Ma) and orangutan (16-17 Ma) reference proteomes, respectively.

RESULTS: Incorrectly suggested amino acid substitutions are absent when employing adequate filtering criteria for mutable Peptide Spectrum Matches (PSMs), but roughly half of the mutable PSMs were not recovered. As a result, peptide and protein identification rates are higher in error-tolerant mode compared to non-error-tolerant searches but did not recover protein identifications completely. Data indicates that peptide length and the number of mutations between the target and database sequences are the main factors influencing mutable PSM identification.

CONCLUSIONS: The error-tolerant results suggest that the cross-species proteomics problem is not overcome at increasing evolutionary distances, even at the protein level. Peptide and protein loss has the potential to significantly impact divergence dating and proteome comparisons when using ancient samples as there is a bias towards the identification of conserved sequences and proteins. Effects are minimized between moderately divergent proteomes, as indicated by almost complete recovery of informative positions in the search against the chimpanzee proteome (≈90%, 6-8 Ma). This provides a bioinformatic background to future phylogenetic and proteomic analysis of ancient hominin proteomes, including the future description of novel hominin amino acid sequences, but also has negative implications for the study of fast-evolving proteins in hominins, non-hominin animals, and ancient bacterial proteins in evolutionary contexts.}, } @article {pmid29463214, year = {2018}, author = {de Oliveira, TB and Gostinčar, C and Gunde-Cimerman, N and Rodrigues, A}, title = {Genome mining for peptidases in heat-tolerant and mesophilic fungi and putative adaptations for thermostability.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {152}, pmid = {29463214}, issn = {1471-2164}, support = {2012/14594-7 and 2015/25252-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2011/16765-0//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; }, mesh = {Adaptation, Biological/*genetics ; Computational Biology/methods ; Databases, Nucleic Acid ; Fungi/classification/genetics/*physiology ; *Genome, Fungal ; Genomics/methods ; Heat-Shock Response/*genetics ; Hot Temperature ; Microbial Viability/genetics ; Peptide Hydrolases/*genetics ; Phylogeny ; }, abstract = {BACKGROUND: Peptidases (EC 3.4) consist of a large group of hydrolytic enzymes that catalyze the hydrolysis of proteins accounting for approximately 65% of the total worldwide enzyme production. Peptidases from thermophilic fungi have adaptations to high temperature that makes them adequate for biotechnological application. In the present study, we profiled the genomes of heat-tolerant fungi and phylogenetically related mesophilic species for genes encoding for peptidases and their putative adaptations for thermostability.

RESULTS: We generated an extensive catalogue of these enzymes ranging from 241 to 820 peptidase genes in the genomes of 23 fungi. Thermophilic species presented the smallest number of peptidases encoding genes in relation to mesophilic species, and the peptidases families with a greater number of genes were the most affected. We observed differences in peptidases in thermophilic species in comparison to mesophilic counterparts, at (i) the genome level: a great reduction in the number of peptidases encoding genes that harbored a higher number of copies; (ii) in the primary protein structure: shifts in proportion of single or groups of amino acids; and (iii) in the three-dimensional structure: reduction in the number of internal cavities. Similar results were reported for extremely thermophilic proteins, but here we show for the first time that several changes also occurred on the moderate thermophilic enzymes of fungi. In regards to the amino acids composition, peptidases from thermophilic species in relation to the mesophilic ones, contained a larger proportion of Ala, Glu, Gly, Pro, Arg and Val residues and a lower number of Cys, His, Ile, Lys, Met, Asn, Gln, Ser, Thr and Trp residues (P < 0.05). Moreover, we observed an increase in the proportion of hydrophobic and charged amino acids and a decrease in polar amino acids.

CONCLUSIONS: Although thermophilic fungi present less genes encoding for peptidases, these have adaptations that could play a role in thermal resistance from genome to protein structure level.}, } @article {pmid29463212, year = {2018}, author = {Wagner, JT and Singh, PP and Romney, AL and Riggs, CL and Minx, P and Woll, SC and Roush, J and Warren, WC and Brunet, A and Podrabsky, JE}, title = {The genome of Austrofundulus limnaeus offers insights into extreme vertebrate stress tolerance and embryonic development.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {155}, pmid = {29463212}, issn = {1471-2164}, support = {IOS-1354549//National Science Foundation/International ; CEHG Fellowship//Stanford University/International ; }, mesh = {Adaptation, Biological/*genetics ; Animals ; Base Composition ; Biological Evolution ; Chickens ; Embryo, Nonmammalian ; Embryonic Development/*genetics ; Gene Expression Regulation ; *Genome ; Genome Size ; Genomics/methods ; Killifishes/*embryology/genetics/*physiology ; Mitochondria/genetics/metabolism ; Phylogeny ; Repetitive Sequences, Nucleic Acid ; Stress, Physiological/*genetics ; Vertebrates ; Zebrafish ; }, abstract = {BACKGROUND: The annual killifish Austrofundulus limnaeus inhabits ephemeral ponds in northern Venezuela, South America, and is an emerging extremophile model for vertebrate diapause, stress tolerance, and evolution. Embryos of A. limnaeus regularly experience extended periods of desiccation and anoxia as a part of their natural history and have unique metabolic and developmental adaptations. Currently, there are limited genomic resources available for gene expression and evolutionary studies that can take advantage of A. limnaeus as a unique model system.

RESULTS: We describe the first draft genome sequence of A. limnaeus. The genome was assembled de novo using a merged assembly strategy and was annotated using the NCBI Eukaryotic Annotation Pipeline. We show that the assembled genome has a high degree of completeness in genic regions that is on par with several other teleost genomes. Using RNA-seq and phylogenetic-based approaches, we identify several candidate genes that may be important for embryonic stress tolerance and post-diapause development in A. limnaeus. Several of these genes include heat shock proteins that have unique expression patterns in A. limnaeus embryos and at least one of these may be under positive selection.

CONCLUSION: The A. limnaeus genome is the first South American annual killifish genome made publicly available. This genome will be a valuable resource for comparative genomics to determine the genetic and evolutionary mechanisms that support the unique biology of annual killifishes. In a broader context, this genome will be a valuable tool for exploring genome-environment interactions and their impacts on vertebrate physiology and evolution.}, } @article {pmid29463208, year = {2018}, author = {Flygare, S and Hernandez, EJ and Phan, L and Moore, B and Li, M and Fejes, A and Hu, H and Eilbeck, K and Huff, C and Jorde, L and G Reese, M and Yandell, M}, title = {The VAAST Variant Prioritizer (VVP): ultrafast, easy to use whole genome variant prioritization tool.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {57}, pmid = {29463208}, issn = {1471-2105}, support = {R4HG003667//National Institutes of Health (US)/International ; R35 GM118335/GM/NIGMS NIH HHS/United States ; RC2HG005619/HG/NHGRI NIH HHS/United States ; R01GM104390/GM/NIGMS NIH HHS/United States ; R01 GM104390/GM/NIGMS NIH HHS/United States ; R44HG002991/NH/NIH HHS/United States ; }, mesh = {Computational Biology/*methods ; Databases, Genetic ; *Genetic Variation ; *Genome, Human ; Humans ; Polymorphism, Single Nucleotide/genetics ; ROC Curve ; *Software ; Time Factors ; Whole Genome Sequencing ; Zygote/metabolism ; }, abstract = {BACKGROUND: Prioritization of sequence variants for diagnosis and discovery of Mendelian diseases is challenging, especially in large collections of whole genome sequences (WGS). Fast, scalable solutions are needed for discovery research, for clinical applications, and for curation of massive public variant repositories such as dbSNP and gnomAD. In response, we have developed VVP, the VAAST Variant Prioritizer. VVP is ultrafast, scales to even the largest variant repositories and genome collections, and its outputs are designed to simplify clinical interpretation of variants of uncertain significance.

RESULTS: We show that scoring the entire contents of dbSNP (> 155 million variants) requires only 95 min using a machine with 4 cpus and 16 GB of RAM, and that a 60X WGS can be processed in less than 5 min. We also demonstrate that VVP can score variants anywhere in the genome, regardless of type, effect, or location. It does so by integrating sequence conservation, the type of sequence change, allele frequencies, variant burden, and zygosity. Finally, we also show that VVP scores are consistently accurate, and easily interpreted, traits not shared by many commonly used tools such as SIFT and CADD.

CONCLUSIONS: VVP provides rapid and scalable means to prioritize any sequence variant, anywhere in the genome, and its scores are designed to facilitate variant interpretation using ACMG and NHS guidelines. These traits make it well suited for operation on very large collections of WGS sequences.}, } @article {pmid29462764, year = {2018}, author = {Jones, DA and Bertazzoni, S and Turo, CJ and Syme, RA and Hane, JK}, title = {Bioinformatic prediction of plant-pathogenicity effector proteins of fungi.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {43-49}, doi = {10.1016/j.mib.2018.01.017}, pmid = {29462764}, issn = {1879-0364}, abstract = {Effector proteins are important virulence factors of fungal plant pathogens and their prediction largely relies on bioinformatic methods. In this review we outline the current methods for the prediction of fungal plant pathogenicity effector proteins. Some fungal effectors have been characterised and are represented by conserved motifs or in sequence repositories, however most fungal effectors do not generally exhibit high conservation of amino acid sequence. Therefore various predictive methods have been developed around: general properties, structure, position in the genomic landscape, and detection of mutations including repeat-induced point mutations and positive selection. A combinatorial approach incorporating several of these methods is often employed and candidates can be prioritised by either ranked scores or hierarchical clustering.}, } @article {pmid29462675, year = {2018}, author = {Khan, G and Zhang, F and Gao, Q and Fu, P and Zhang, Y and Chen, S}, title = {Spiroides shrubs on Qinghai-Tibetan Plateau: Multilocus phylogeography and palaeodistributional reconstruction of Spiraea alpina and S. Mongolica (Rosaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {137-148}, doi = {10.1016/j.ympev.2018.02.009}, pmid = {29462675}, issn = {1095-9513}, mesh = {Bayes Theorem ; Biodiversity ; Climate ; Climate Change ; DNA, Chloroplast/genetics ; Evolution, Molecular ; *Genetic Loci ; Genetic Variation ; Haplotypes/genetics ; Likelihood Functions ; Models, Theoretical ; *Paleontology ; Phylogeny ; *Phylogeography ; Sequence Analysis, DNA ; Spiraea/*classification/*genetics ; Tibet ; Time Factors ; }, abstract = {A common hypothesis for the rich biodiversity found in mountains is uplift-driven diversification. Using a multilocus approach, here we assessed the influence of Qinghai-Tibetan Plateau (QTP) uplift and fluctuating regional climate on genetic diversity of two sister spiroides shrubs, Spiraea alpina and S. mongolica. Combined with palaeodistributional reconstruction modelling, we investigated the current and past-predicted distribution of these species under different climatic episodes. The study demonstrated that continuous pulses of retreat and expansion during last glacial-interglacial episodes, combined with the uplifting of QTP shaped the current distribution of these species. All the populations showed high level of genetic diversity based on both cpDNA and SSR markers. The average gene diversity within populations based on cpDNA markers was 0.383 ± 0.052 for S. alpina and 0.477 ± 0.048 for S. mongolica. The observed and expected heterozygosities based on SSR for both Spiraea alpina and S. mongolicawere HE(0.72-0.90)/HO(0.35-0.78) and HE(0.77-0.92)/HO(0.47-0.77) respectively. Palaeodistributional reconstruction indicated species' preferences at southeastern edge of the plateau during last glacial maximum, at higher altitude areas of QTP and range expansion to central plateau during the interglacial episodes. Assignment tests in STRUCTURE, discriminant analysis of principal coordinates and Immigrants analysis in GENECLASS based on nuclear SSR markers did not support the hypothesis of gene flow between both the species. However, maximum likelihood approach based on cpDNA showed sharing of haplotypes between both species.}, } @article {pmid29462332, year = {2018}, author = {Liu, Y and Chi, H and Li, L and Rossiter, SJ and Zhang, S}, title = {Molecular Data Support an Early Shift to an Intermediate-Light Niche in the Evolution of Mammals.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1130-1134}, doi = {10.1093/molbev/msy019}, pmid = {29462332}, issn = {1537-1719}, abstract = {The visual ability and associated photic niche of early mammals is debated. The theory that ancestral mammals were nocturnal is supported by diverse adaptations. However, others argue that photopigment repertoires of early mammals are more consistent with a crepuscular niche, and support for this also comes from inferred spectral tuning of middle/long wavelength-sensitive (M/LWS) opsin sequences. Functional studies have suggested that the M/LWS pigment in the ancestor of Mammalia was either red- or green-sensitive; however, these were based on outdated phylogenies with key lineages omitted. By performing the most detailed study to date of middle/long-wave mammalian color vision, we provide the first experimental evidence that the M/LWS pigment of amniotes underwent a 9-nm spectral shift towards shorter wavelengths in the Mammalia ancestor, exceeding predictions from known critical sites. Our results suggest early mammals were yellow-sensitive, possibly representing an adaptive trade-off for both crepuscular (twilight) and nocturnal (moonlight) niches.}, } @article {pmid29462328, year = {2018}, author = {}, title = {Different genomic changes underlie adaptive evolution in populations of contrasting history.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msy012}, pmid = {29462328}, issn = {1537-1719}, } @article {pmid29462310, year = {2018}, author = {Wolters, B and Jacquiod, S and Sørensen, SJ and Widyasari-Mehta, A and Bech, TB and Kreuzig, R and Smalla, K}, title = {Bulk soil and maize rhizosphere resistance genes, mobile genetic elements and microbial communities are differently impacted by organic and inorganic fertilization.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy027}, pmid = {29462310}, issn = {1574-6941}, abstract = {Organic soil fertilizers, such as livestock manure and biogas digestate, frequently contain bacteria carrying resistance genes (RGs) to antimicrobial substances and mobile genetic elements (MGEs). The effects of different fertilizers (inorganic, manure, digestate) on RG and MGE abundance and microbial community composition were investigated in a field plot experiment. The relative abundances of RGs [sul1, sul2, tet(A), tet(M), tet(Q), tet(W), qacEΔ1/qacE] and MGEs [intI1, intI2, IncP-1, IncP-1ε and LowGC plasmids] in total community (TC)-DNA from organic fertilizers, bulk soil and maize rhizosphere were quantified by qPCR before/after fertilization and prior to maize harvest. Microbial communities were analyzed via Illumina sequencing of 16S rRNA gene fragments amplified from TC-DNA. Compared to inorganic fertilization, manure treatments increased relative abundances of all RGs analyzed, integrons and few genera affiliated to Bacteroidetes and Firmicutes in bulk soil, while digestate increased sul2, tet(W) and intI2. At harvest, treatment effects vanished in bulk soil. However, organic fertilizer effects were still detectable in the rhizosphere for RGs [manure: intI1, sul1; digestate: tet(W)] and Clostridium related sequences (digestates) with increased relative abundance. Our data indicated transient organic fertilizer effects on RGs, MGEs and microbial community composition in bulk soil with long-term history of digestate or manure application.}, } @article {pmid29462300, year = {2018}, author = {Chen, SC and Duan, GL and Ding, K and Huang, FY and Zhu, YG}, title = {DNA stable-isotope probing identifies uncultivated members of Pseudonocardia associated with biodegradation of pyrene in agricultural soil.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy026}, pmid = {29462300}, issn = {1574-6941}, abstract = {Identifying functional microorganisms involved in the degradation of high-molecular-mass polycyclic aromatic hydrocarbons (HMM-PAHs) in agricultural soil environments could assist in developing bioremediation strategies for soil PAH contamination. Active populations of HMM-PAH degraders in agricultural soils are currently poorly understood. In this study, we identified aerobic pyrene-degrading bacteria in agricultural and industrial soils by [13C]pyrene incubations followed by DNA stable-isotope probing and high-throughput sequencing. More than 80% of pyrene was degraded during an incubation time of 35 days in both soils, with slower mineralization rates observed in agricultural soil compared with industrial soil. Members of the Pseudonocardia genus, not previously implicated in pyrene degradation, were the dominant pyrene-degrading population in agricultural soil; their relative abundance increased by three orders of magnitude. In industrial soil, Arthrobacter sp. appeared as the major pyrene degraders, while Pseudonocardia was not detectable. Mycobacterium, a group of well-known pyrene degraders, was found to be active in pyrene degradation in both soils. These results highlight the role of uncultivated members of Pseudonocardia in natural PAH biodegradation processes and expand our understanding of the metabolic potential of uncultivated microorganisms for bioremediation applications in agricultural soils.}, } @article {pmid29461638, year = {2018}, author = {Rosenthal, MF and Wilkins, MR and Shizuka, D and Hebets, EA}, title = {Dynamic changes in display architecture and function across environments revealed by a systems approach to animal communication.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1134-1145}, doi = {10.1111/evo.13448}, pmid = {29461638}, issn = {1558-5646}, abstract = {Animal communication is often structurally complex and dynamic, with signaler and receiver behavior varying in response to multiple environmental factors. To date, studies assessing signal dynamics have mostly focused on the relationships between select signaling traits and receiver responses in a single environment. We use the wolf spider Schizocosa floridana to explore the relationships between courtship display form and function across two social contexts (female presence vs absence) and two light environments (light vs dark). We use traditional analytical methods to determine predictors of copulation success (i.e., signal function) and examine these predictors in a structural context by overlaying them on signal phenotype networks (Wilkins et al. 2015). This allows us to explore system design principles (degeneracy, redundancy, pluripotentiality), providing insight into hypotheses regarding complex signal evolution. We found that both social context and light environment affect courtship structure, although the predictors of mating success remain similar across light environments, suggesting system degeneracy. Contrastingly, the same display traits may serve different functions across social environments, suggesting pluripotentiality. Ultimately, our network approach uncovers a complexity in display structure and function that is missed by functional analyses alone, highlighting the importance of systems-based methodologies for understanding the dynamic nature of complex signals.}, } @article {pmid29461186, year = {2018}, author = {Khunnamwong, P and Limtong, S}, title = {Saturnispora kantuleensis f.a., sp. nov., a novel yeast species isolated from peat in a tropical peat swamp forest in Thailand.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1160-1164}, doi = {10.1099/ijsem.0.002641}, pmid = {29461186}, issn = {1466-5034}, mesh = {DNA, Fungal/genetics ; DNA, Ribosomal Spacer/genetics ; Mycological Typing Techniques ; *Phylogeny ; Saccharomycetales/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; *Soil ; Thailand ; *Wetlands ; }, abstract = {Two strains (DMKU-PPS4-5T and DMKU-EPS3-4) representing a single novel anamorphic yeast species were isolated from two peat samples collected in Kan Tulee peat swamp forest, Surat Thani Province, Thailand. The strains differed by two nucleotide substitutions in the sequences of the D1/D2 region of the large subunit (LSU) rRNA gene and only one nucleotide substitution in the internal transcribed spacer (ITS) region. Phylogenetic analysis based on the D1/D2 regions showed that the two strains represented a single species in the genus Saturnispora and were clearly distinct from other related species. Saturnispora sekii was the most closely related species, but with 1.7-2.1 % nucleotide substitutions in the D1/D2 region of the LSU rRNA gene, and 3.1-3.3 % nucleotide substitutions in the ITS region. They therefore represent a novel species of the genus Saturnispora, although the formation of ascospores was not observed. The name Saturnispora kantuleensis f.a., sp. nov. is proposed. The type strain is DMKU-PPS4-5T (=CBS 15217T=TBRC 7762T).}, } @article {pmid29461184, year = {2018}, author = {Liu, Q and Xin, YH and Chen, XL and Liu, HC and Zhou, YG and Chen, WX}, title = {Cryobacterium aureum sp. nov., a psychrophilic bacterium isolated from glacier ice collected from the ice tongue surface.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1173-1176}, doi = {10.1099/ijsem.0.002647}, pmid = {29461184}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Ice Cover/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {A psychrophilic, Gram-stain-positive, rod-shaped bacterium, designated strain Hh31T, was isolated from Xinjiang No. 1 Glacier in China. Strain Hh31T was catalase-positive, oxidase-negative and able to grow at between 0-18 °C. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain Hh31T belonged to the genus Cryobacterium and was most closely related to the type strains of Cryobacterium levicorallinum, Cryobacterium luteum and Cryobacterium flavum. DNA-DNA hybridization, calculation of average nucleotide identity and digital DNA-DNA hybridization revealed that strain Hh31T was distinct from its closest phylogenetic neighbours. The major cellular fatty acids of strain Hh31T were anteiso-C15 : 0, anteiso-C15 : 1, iso-C15:0, iso-C16 : 0 and anteiso-C17 : 0. The predominant menaquinones of strain Hh31T were MK-9 and MK-10. The polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, one unidentified phospholipid, one unidentified glycolipid and another unidentified lipid. Physiological tests such as carbon source utilization, showed phenotypic differentiation of strain Hh31T from the closest related phylogenetic neighbours. Based on a polyphasic approach, a novel species, Cryobacterium aureum sp. nov., is proposed, with Hh31T (=NBRC 107882T=CGMCC 1.11213T) as the type strain.}, } @article {pmid29461183, year = {2018}, author = {Shen, X and Zhao, Z and Wu, C and Yu, XY and Li, Y and Sun, C and Wu, M}, title = {Roseovarius nitratireducens sp. nov., a halotolerant bacterium isolated from a saline lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002651}, pmid = {29461183}, issn = {1466-5034}, abstract = {A Gram-stain-negative, aerobic, non-motile and ovoid- to rod-shaped bacterial strain, designated TFZT, was isolated from a water sample of a saline lake in Xinjiang, China and subjected to polyphasic taxonomic investigation. Strain TFZT grew at 4-42 °C and pH 6.5-10.0 (optimum, 30 °C and pH 7.0) and with 0.5-18.0 % (w/v) NaCl (optimum, 1.5 %). According to phylogenetic analysis based on 16S rRNA gene sequences, strain TFZT was assigned to the genus Roseovarius with highest 16S rRNA gene sequence similarity of 97.5 % to Roseovarius tolerans EL-172T, followed by Roseovarius azorensis SSW084T (96.6 %) and Roseovarius mucosus DSM 17069T (95.5 %). Digital DNA-DNA hybridization (DDH) and average nucleotide identity (ANI) were determined to evaluate the genomic relationship between strain TFZT and R. tolerans EL-172T. Digital DDH estimation (22.80±2.35 %) as well as ANI (80.1 %) proved the dissimilarity of strain TFZT. Chemotaxonomic analysis showed that strain TFZT contained ubiquinone-10 as the predominant respiratory quinone and possessed summed feature 8 (comprising C18 : 1ω7c and/or ω6c) and C16 : 0 as the predominant form of fatty acid. The polar lipids of strain TFZT consisted of phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and five unidentified lipids. The DNA G+C content was 65.4 mol% (by genome sequencing). Based on the polyphasic taxonomic characterization, strain TFZT is considered to represent a novel species of the genus Roseovarius, for which the name Roseovariusnitratireducens sp. nov. is proposed (type strain TFZT=MCCC 1K03339T=KCTC 52967T).}, } @article {pmid29461181, year = {2018}, author = {Lee, Y and Jeon, CO}, title = {Paraburkholderia aromaticivorans sp. nov., an aromatic hydrocarbon-degrading bacterium, isolated from gasoline-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1251-1257}, doi = {10.1099/ijsem.0.002661}, pmid = {29461181}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Burkholderiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gasoline/*microbiology ; Hydrocarbons, Aromatic/*metabolism ; Nucleic Acid Hybridization ; Petroleum Pollution ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, facultatively aerobic, aromatic hydrocarbon-degrading bacterium, designated strain BN5T, was isolated from gasoline-contaminated soil. Cells were motile and slightly curved rods with a single flagellum showing catalase and oxidase activities. Growth was observed at 20-37 °C (optimum, 25-30 °C), pH 3-7 (optimum, pH 5-6) and 0-2 % NaCl (optimum, 0 %). Ubiquinone-8 was the predominant respiratory quinone. The major fatty acids were C16 : 0, cyclo-C19 : 0ω8c and summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c). Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, an unidentified phosphoamino lipid, three unidentified amino lipids and eight unidentified lipids were the identified polar lipids. The DNA G+C content was 62.93 mol%. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain BN5T formed a phylogenic lineage with members of the genus Paraburkholderia and showed the highest 16S rRNA gene sequence similarities to Paraburkholderia phytofirmans PsJNT (99.4 %), Paraburkholderia dipogonis DL7T (98.8 %) and Paraburkholderia insulsa PNG-AprilT (98.8 %). The average nucleotide identity and in silico DNA-DNA hybridization (DDH) values between strain BN5T and P. phytofirmans PsJNT were 88.5 and 36.5 %, respectively. The DDH values for strain BN5T with P. dipogonis LMG 28415T and P. insulsa DSM 28142T were 41.0±4.9 % (reciprocal, 33.0±4.3 %) and 47.1±6.6 % (reciprocal, 51.7±5.4 %), respectively. Based on its physiological, chemotaxonomic and phylogenetic features, we conclude that strain BN5T is a novel species of the genus Paraburkholderia, for which the name Paraburkholderia aromaticivorans sp. nov. is proposed. The type strain is BN5T (=KACC 19419T=JCM 32303T).}, } @article {pmid29461180, year = {2018}, author = {Yuan, K and Cao, M and Li, J and Wang, G}, title = {Pedobacter mongoliensis sp. nov., isolated from grassland soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1112-1117}, doi = {10.1099/ijsem.0.002637}, pmid = {29461180}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; *Grassland ; Pedobacter/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, motile by gliding and strictly aerobic bacterial strain, named 1-32T, was isolated from soil of the Ordos grassland in Inner Mongolia, PR China. Strain 1-32T showed highest 16S rRNA gene sequence similarities to Pedobacter luteus N7d-4T (95.4 %), Pedobacter oryzae DSM 19973T (95.3 %), 'Pedobacter xinjiangensis' 12157T (95.2 %) and Pedobacter tournemirensis TF5-37.2-LB10T (95.1 %). Phylogenetic analyses clustered strain 1-32T with 'P. xinjiangensis' 12157T and P. tournemirensis TF5-37.2-LB10T. The DNA G+C content was 43.4 mol%. Menaquinone 7 was the main respiratory quinone. The predominant fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), iso-C17 : 0 3-OH, iso-C15 : 0 3-OH and C16 : 1ω5c. The polar lipids of strain 1-32T comprised phosphatidylethanolamine, two unidentified polar lipids, one unidentified glycolipid and two unidentified phospholipids. Strain 1-32T could be distinguished from the other members of the genus Pedobacter based on its phylogenetic distance and physiological and biochemical characteristics such as being negative for the assimilation of rhamnose and the activity of α-glucosidase. Therefore, strain 1-32T represents a novel species of the genus Pedobacter, for which the name Pedobacter mongoliensis sp. nov. is proposed. The type strain is 1-32T (=KCTC 52859T=CCTCC AB 2017084T).}, } @article {pmid29461179, year = {2018}, author = {Rochman, FF and Kim, JJ and Rijpstra, WIC and Sinninghe Damsté, JS and Schumann, P and Verbeke, TJ and Dunfield, PF}, title = {Oleiharenicola alkalitolerans gen. nov., sp. nov., a new member of the phylum Verrucomicrobia isolated from an oilsands tailings pond.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002624}, pmid = {29461179}, issn = {1466-5034}, abstract = {A novel member of the phylum Verrucomicrobia was isolated from an oilsands tailings pond in Alberta, Canada. Cells of isolate NVTT are Gram-negative, strictly aerobic, non-pigmented, non-motile cocci to diplococci 0.5-1.0 µm in diameter. The bacterium is neutrophilic (optimum pH 6.0-8.0) but alkalitolerant, capable of growth between pH 5.5 and 11.0. The temperature range for growth is 15-40 °C (optimum 25-37 °C). Carbon and energy sources include sugars and organic acids. Nitrogen sources include nitrate, urea, l-glycine, l-alanine, l-proline and l-serine. Does not fix atmospheric nitrogen. Does not require NaCl and is inhibited at NaCl concentrations above 3.0 % (w/v). The DNA G+C content of strain NVTT, based on a draft genome sequence, is 66.1 mol%. MK-6 and MK-7 are the major respiratory quinones. Major cellular fatty acids are anteiso-C15 : 0 and iso-C15 : 0. Phylogenetic analysis of 16S rRNA gene sequences revealed that the strain belongs to the family Opitutaceae of the phylum Verrucomicrobia. The most closely related validated species is Opitutus terrae (93.7 % 16S rRNA gene sequence identity to its type strain PB90-1T). Based on genotypic, phenotypic and chemotaxonomic characteristics, it was concluded that this strain represents a novel genus and species, for which the name Oleiharenicola alkalitolerans gen. nov., sp. nov. is proposed. The type strain of this novel species is NVTT (=ATCC BAA-2697T;=DSM 29249T).}, } @article {pmid29460507, year = {2018}, author = {Gibson, AK and Stoy, KS and Lively, CM}, title = {Bloody-minded parasites and sex: the effects of fluctuating virulence.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {611-620}, pmid = {29460507}, issn = {1420-9101}, support = {K12 GM000680/GM/NIGMS NIH HHS/United States ; }, abstract = {Asexual lineages can grow at a faster rate than sexual lineages. Why then is sexual reproduction so widespread? Much empirical evidence supports the Red Queen hypothesis. Under this hypothesis, coevolving parasites favour sexual reproduction by adapting to infect common asexual clones and driving them down in frequency. One limitation, however, seems to challenge the generality of the Red Queen: in theoretical models, parasites must be very virulent to maintain sex. Moreover, experiments show virulence to be unstable, readily shifting in response to environmental conditions. Does variation in virulence further limit the ability of coevolving parasites to maintain sex? To address this question, we simulated temporal variation in virulence and evaluated the outcome of competition between sexual and asexual females. We found that variation in virulence did not limit the ability of coevolving parasites to maintain sex. In fact, relatively high variation in virulence promoted parasite-mediated maintenance of sex. With sufficient variation, sexual females persisted even when mean virulence fell well below the threshold virulence required to maintain sex under constant conditions. We conclude that natural variation in virulence does not limit the relevance of the Red Queen hypothesis for natural populations; on the contrary, it could expand the range of conditions over which coevolving parasites can maintain sex.}, } @article {pmid29460123, year = {2018}, author = {Larsen, PA and Hunnicutt, KE and Larsen, RJ and Yoder, AD and Saunders, AM}, title = {Warning SINEs: Alu elements, evolution of the human brain, and the spectrum of neurological disease.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {1-2}, pages = {93-111}, pmid = {29460123}, issn = {1573-6849}, support = {S10 OD018164/OD/NIH HHS/United States ; }, mesh = {Alu Elements/*physiology ; *Biological Evolution ; Brain/*physiology ; Genome, Human ; Humans ; Nervous System Diseases/*genetics ; Neurogenesis ; Retroelements ; }, abstract = {Alu elements are a highly successful family of primate-specific retrotransposons that have fundamentally shaped primate evolution, including the evolution of our own species. Alus play critical roles in the formation of neurological networks and the epigenetic regulation of biochemical processes throughout the central nervous system (CNS), and thus are hypothesized to have contributed to the origin of human cognition. Despite the benefits that Alus provide, deleterious Alu activity is associated with a number of neurological and neurodegenerative disorders. In particular, neurological networks are potentially vulnerable to the epigenetic dysregulation of Alu elements operating across the suite of nuclear-encoded mitochondrial genes that are critical for both mitochondrial and CNS function. Here, we highlight the beneficial neurological aspects of Alu elements as well as their potential to cause disease by disrupting key cellular processes across the CNS. We identify at least 37 neurological and neurodegenerative disorders wherein deleterious Alu activity has been implicated as a contributing factor for the manifestation of disease, and for many of these disorders, this activity is operating on genes that are essential for proper mitochondrial function. We conclude that the epigenetic dysregulation of Alu elements can ultimately disrupt mitochondrial homeostasis within the CNS. This mechanism is a plausible source for the incipient neuronal stress that is consistently observed across a spectrum of sporadic neurological and neurodegenerative disorders.}, } @article {pmid29460038, year = {2018}, author = {Avni, E and Yona, Z and Cohen, R and Snir, S}, title = {The Performance of Two Supertree Schemes Compared Using Synthetic and Real Data Quartet Input.}, journal = {Journal of molecular evolution}, volume = {86}, number = {2}, pages = {150-165}, pmid = {29460038}, issn = {1432-1432}, abstract = {Despite impressive advancements in technological and theoretical tools, construction of phylogenetic (evolutionary) trees is still a challenging task. The availability of enormous quantities of molecular data has made large-scale phylogenetic reconstruction involving thousands of species, a more viable goal. For this goal, separate trees over different, overlapping subsets of species, representing histories of various markers of these species, are collected. These trees, typically with conflicting signals, are subsequently combined into a single tree over the full set, an operation denoted as supertree construction. The amalgamation of such trees into a single tree lies at the heart of many tasks in phylogenetics, yet remains a daunting endeavor, especially in light of conflicting signals. In this work, we study the performance of matrix representation with parsimony (MRP), the most widely used supertree method to date, when confronted with quartet trees. Quartet trees are the most basic informational unit when amalgamation of unrooted trees is attempted, and they remain relevant in more general settings even though standard supertree methods are not necessarily confined to quartets. This study involves both real and simulated data, and the effects of several parameters on the results are evaluated, revealing a number of anomalies associated with MRP. We show that these anomalies are surmountable when using a recently introduced supertree method, weighted quartet MaxCut (wQMC).}, } @article {pmid29459733, year = {2018}, author = {LaCourse, KD and Peterson, SB and Kulasekara, HD and Radey, MC and Kim, J and Mougous, JD}, title = {Conditional toxicity and synergy drive diversity among antibacterial effectors.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {440-446}, pmid = {29459733}, issn = {2058-5276}, support = {//Howard Hughes Medical Institute/United States ; R01 AI080609/AI/NIAID NIH HHS/United States ; T32 GM007270/GM/NIGMS NIH HHS/United States ; }, abstract = {Bacteria in polymicrobial habitats contend with a persistent barrage of competitors, often under rapidly changing environmental conditions 1 . The direct antagonism of competitor cells is thus an important bacterial survival strategy 2 . Towards this end, many bacterial species employ an arsenal of antimicrobial effectors with multiple activities; however, the benefits conferred by the simultaneous deployment of diverse toxins are unknown. Here we show that the multiple effectors delivered to competitor bacteria by the type VI secretion system (T6SS) of Pseudomonas aeruginosa display conditional efficacy and act synergistically. One of these effectors, Tse4, is most active in high-salinity environments and synergizes with effectors that degrade the cell wall or inactivate intracellular electron carriers. We find Tse4 synergizes with these disparate mechanisms by forming pores that disrupt the ΔΨ component of the proton motive force. Our results provide evidence that the concomitant delivery of a cocktail of effectors serves as a bet-hedging strategy to promote bacterial competitiveness in the face of unpredictable and variable environmental conditions.}, } @article {pmid29459732, year = {2018}, author = {Thomas, JA and Tan, MSY and Bisson, C and Borg, A and Umrekar, TR and Hackett, F and Hale, VL and Vizcay-Barrena, G and Fleck, RA and Snijders, AP and Saibil, HR and Blackman, MJ}, title = {A protease cascade regulates release of the human malaria parasite Plasmodium falciparum from host red blood cells.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {447-455}, pmid = {29459732}, issn = {2058-5276}, support = {FC001043//Wellcome Trust/United Kingdom ; G1100013//Medical Research Council/United Kingdom ; FC001043//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; FC001043//Cancer Research UK/United Kingdom ; }, abstract = {Malaria parasites replicate within a parasitophorous vacuole in red blood cells (RBCs). Progeny merozoites egress upon rupture of first the parasitophorous vacuole membrane (PVM), then poration and rupture of the RBC membrane (RBCM). Egress is protease-dependent 1 , but none of the effector molecules that mediate membrane rupture have been identified and it is unknown how sequential rupture of the two membranes is controlled. Minutes before egress, the parasite serine protease SUB1 is discharged into the parasitophorous vacuole2-6 where it cleaves multiple substrates2,5,7-9 including SERA6, a putative cysteine protease10-12. Here, we show that Plasmodium falciparum parasites lacking SUB1 undergo none of the morphological transformations that precede egress and fail to rupture the PVM. In contrast, PVM rupture and RBCM poration occur normally in SERA6-null parasites but RBCM rupture does not occur. Complementation studies show that SERA6 is an enzyme that requires processing by SUB1 to function. RBCM rupture is associated with SERA6-dependent proteolytic cleavage within the actin-binding domain of the major RBC cytoskeletal protein β-spectrin. We conclude that SUB1 and SERA6 play distinct, essential roles in a coordinated proteolytic cascade that enables sequential rupture of the two bounding membranes and culminates in RBCM disruption through rapid, precise, SERA6-mediated disassembly of the RBC cytoskeleton.}, } @article {pmid29459710, year = {2018}, author = {Sommer, RS and Hegge, C and Schmölcke, U}, title = {Lack of support for adaptation of post-glacial horses to woodlands.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {582-583}, doi = {10.1038/s41559-018-0491-9}, pmid = {29459710}, issn = {2397-334X}, } @article {pmid29459709, year = {2018}, author = {VanKuren, NW and Long, M}, title = {Gene duplicates resolving sexual conflict rapidly evolved essential gametogenesis functions.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {705-712}, pmid = {29459709}, issn = {2397-334X}, support = {R01 GM100768/GM/NIGMS NIH HHS/United States ; R01 GM116113/GM/NIGMS NIH HHS/United States ; T32 GM007197/GM/NIGMS NIH HHS/United States ; }, abstract = {Males and females have different fitness optima but share the vast majority of their genomes, causing an inherent genetic conflict between the two sexes that must be resolved to achieve maximal population fitness. We show that two tandem duplicate genes found specifically in Drosophila melanogaster are sexually antagonistic, but rapidly evolved sex-specific functions and expression patterns that mitigate their antagonistic effects. We use copy-specific knockouts and rescue experiments to show that Apollo (Apl) is essential for male fertility but detrimental to female fertility, in addition to its important role in development, while Artemis (Arts) is essential for female fertility but detrimental to male fertility. Further analyses show that Apl and Arts have essential roles in spermatogenesis and oogenesis. These duplicates formed ~200,000 years ago, underwent a strong selective sweep and lost most expression in the antagonized sex. These data provide direct evidence that gene duplication allowed rapid mitigation of sexual conflict by allowing Apl and Arts to evolve essential sex-specific reproductive functions and complementary expression in male and female gonads.}, } @article {pmid29459708, year = {2018}, author = {Johnson, KE and Voight, BF}, title = {Patterns of shared signatures of recent positive selection across human populations.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {713-720}, pmid = {29459708}, issn = {2397-334X}, support = {R01 DK101478/DK/NIDDK NIH HHS/United States ; T32 GM008216/GM/NIGMS NIH HHS/United States ; }, abstract = {Signatures of recent positive selection often overlap across human populations, but the question of how often these overlaps represent a single ancestral event remains unresolved. If a single selective event spread across many populations, the same sweeping haplotype should appear in each population and the selective pressure could be common across populations and environments. Identifying such shared selective events could identify genomic loci and human traits important in recent history across the globe. In addition, genomic annotations that recently became available could help attach these signatures to a potential gene and molecular phenotype selected across populations. Here, we present a catalogue of selective sweeps in humans, and identify those that overlap and share a sweeping haplotype. We connect these sweep overlaps with potential biological mechanisms at several loci, including potential new sites of adaptive introgression, the glycophorin locus associated with malarial resistance and the alcohol dehydrogenase cluster associated with alcohol dependency.}, } @article {pmid29459707, year = {2018}, author = {Zepeda Mendoza, ML and Xiong, Z and Escalera-Zamudio, M and Runge, AK and Thézé, J and Streicker, D and Frank, HK and Loza-Rubio, E and Liu, S and Ryder, OA and Samaniego Castruita, JA and Katzourakis, A and Pacheco, G and Taboada, B and Löber, U and Pybus, OG and Li, Y and Rojas-Anaya, E and Bohmann, K and Carmona Baez, A and Arias, CF and Liu, S and Greenwood, AD and Bertelsen, MF and White, NE and Bunce, M and Zhang, G and Sicheritz-Pontén, T and Gilbert, MPT}, title = {Hologenomic adaptations underlying the evolution of sanguivory in the common vampire bat.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {659-668}, pmid = {29459707}, issn = {2397-334X}, support = {//Wellcome Trust/United Kingdom ; 681396//European Research Council/International ; }, abstract = {Adaptation to specialized diets often requires modifications at both genomic and microbiome levels. We applied a hologenomic approach to the common vampire bat (Desmodus rotundus), one of the only three obligate blood-feeding (sanguivorous) mammals, to study the evolution of its complex dietary adaptation. Specifically, we assembled its high-quality reference genome (scaffold N50 = 26.9 Mb, contig N50 = 36.6 kb) and gut metagenome, and compared them against those of insectivorous, frugivorous and carnivorous bats. Our analyses showed a particular common vampire bat genomic landscape regarding integrated viral elements, a dietary and phylogenetic influence on gut microbiome taxonomic and functional profiles, and that both genetic elements harbour key traits related to the nutritional (for example, vitamin and lipid shortage) and non-nutritional (for example, nitrogen waste and osmotic homeostasis) challenges of sanguivory. These findings highlight the value of a holistic study of both the host and its microbiota when attempting to decipher adaptations underlying radical dietary lifestyles.}, } @article {pmid29459706, year = {2018}, author = {Burns, JA and Pittis, AA and Kim, E}, title = {Gene-based predictive models of trophic modes suggest Asgard archaea are not phagocytotic.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {697-704}, doi = {10.1038/s41559-018-0477-7}, pmid = {29459706}, issn = {2397-334X}, abstract = {With the current explosion of genomic data, there is a greater need to draw inference on phenotypic information based on DNA sequence alone. We considered complete genomes from 35 diverse eukaryotic lineages, and discovered sets of proteins predictive of trophic mode, including a set of 485 proteins that are enriched among phagocytotic eukaryotes (organisms that internalize large particles). Our model is also predictive of other aspects of trophic mode, including photosynthesis and the ability to synthesize a set of organic compounds needed for growth (prototrophy for those molecules). We applied our model to the Asgard archaea, a group of uncultured microorganisms that show close affinities to eukaryotes, to test whether the organisms are capable of phagocytosis, a phenotypic trait often considered a prerequisite for mitochondrial acquisition. Our analyses suggest that members of the Asgard archaea-despite having some eukaryote-specific protein families not found in other prokaryotes-do not use phagocytosis. Moreover, our data suggest that the process of phagocytosis arose from a combination of both archaeal and bacterial components, but also required additional eukaryote-specific innovations.}, } @article {pmid29459705, year = {2018}, author = {Perry, JC}, title = {Duplication resolves conflict.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {597-598}, doi = {10.1038/s41559-018-0493-7}, pmid = {29459705}, issn = {2397-334X}, } @article {pmid29459681, year = {2018}, author = {Han, L and Ren, C and Li, L and Li, X and Ge, J and Wang, H and Miao, YL and Guo, X and Moley, KH and Shu, W and Wang, Q}, title = {Embryonic defects induced by maternal obesity in mice derive from Stella insufficiency in oocytes.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {432-442}, doi = {10.1038/s41588-018-0055-6}, pmid = {29459681}, issn = {1546-1718}, abstract = {Maternal obesity can impair embryo development and offspring health, yet the mechanisms responsible remain poorly understood. In a high-fat diet (HFD)-based female mouse model of obesity, we identified a marked reduction of Stella (also known as DPPA3 or PGC7) protein in oocytes. Starting with this clue, we found that the establishment of pronuclear epigenetic asymmetry in zygotes from obese mice was severely disrupted, inducing the accumulation of maternal 5-hydroxymethylcytosine modifications and DNA lesions. Furthermore, methylome-wide sequencing analysis detected global hypomethylation across the zygote genome in HFD-fed mice, with a specific enrichment in transposon elements and unique regions. Notably, overexpression of Stella in the oocytes of HFD-fed mice not only restored the epigenetic remodeling in zygotes but also partly ameliorated the maternal-obesity-associated developmental defects in early embryos and fetal growth. Thus, Stella insufficiency in oocytes may represent a critical mechanism that mediates the phenotypic effects of maternal obesity in embryos and offspring.}, } @article {pmid29459680, year = {2018}, author = {Claes, P and Roosenboom, J and White, JD and Swigut, T and Sero, D and Li, J and Lee, MK and Zaidi, A and Mattern, BC and Liebowitz, C and Pearson, L and González, T and Leslie, EJ and Carlson, JC and Orlova, E and Suetens, P and Vandermeulen, D and Feingold, E and Marazita, ML and Shaffer, JR and Wysocka, J and Shriver, MD and Weinberg, SM}, title = {Genome-wide mapping of global-to-local genetic effects on human facial shape.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {414-423}, pmid = {29459680}, issn = {1546-1718}, support = {R01 DE027023/DE/NIDCR NIH HHS/United States ; U01 DE024430/DE/NIDCR NIH HHS/United States ; U01 DE020078/DE/NIDCR NIH HHS/United States ; K99 DE025060/DE/NIDCR NIH HHS/United States ; HHSN268201200008C/HL/NHLBI NIH HHS/United States ; R01 DE016148/DE/NIDCR NIH HHS/United States ; R00 DE025060/DE/NIDCR NIH HHS/United States ; HHSN268201200008I/HL/NHLBI NIH HHS/United States ; U01 DE020057/DE/NIDCR NIH HHS/United States ; }, abstract = {Genome-wide association scans of complex multipartite traits like the human face typically use preselected phenotypic measures. Here we report a data-driven approach to phenotyping facial shape at multiple levels of organization, allowing for an open-ended description of facial variation while preserving statistical power. In a sample of 2,329 persons of European ancestry, we identified 38 loci, 15 of which replicated in an independent European sample (n = 1,719). Four loci were completely new. For the others, additional support (n = 9) or pleiotropic effects (n = 2) were found in the literature, but the results reported here were further refined. All 15 replicated loci highlighted distinctive patterns of global-to-local genetic effects on facial shape and showed enrichment for active chromatin elements in human cranial neural crest cells, suggesting an early developmental origin of the facial variation captured. These results have implications for studies of facial genetics and other complex morphological traits.}, } @article {pmid29459679, year = {2018}, author = {Bouwman, AC and Daetwyler, HD and Chamberlain, AJ and Ponce, CH and Sargolzaei, M and Schenkel, FS and Sahana, G and Govignon-Gion, A and Boitard, S and Dolezal, M and Pausch, H and Brøndum, RF and Bowman, PJ and Thomsen, B and Guldbrandtsen, B and Lund, MS and Servin, B and Garrick, DJ and Reecy, J and Vilkki, J and Bagnato, A and Wang, M and Hoff, JL and Schnabel, RD and Taylor, JF and Vinkhuyzen, AAE and Panitz, F and Bendixen, C and Holm, LE and Gredler, B and Hozé, C and Boussaha, M and Sanchez, MP and Rocha, D and Capitan, A and Tribout, T and Barbat, A and Croiseau, P and Drögemüller, C and Jagannathan, V and Vander Jagt, C and Crowley, JJ and Bieber, A and Purfield, DC and Berry, DP and Emmerling, R and Götz, KU and Frischknecht, M and Russ, I and Sölkner, J and Van Tassell, CP and Fries, R and Stothard, P and Veerkamp, RF and Boichard, D and Goddard, ME and Hayes, BJ}, title = {Meta-analysis of genome-wide association studies for cattle stature identifies common genes that regulate body size in mammals.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {362-367}, doi = {10.1038/s41588-018-0056-5}, pmid = {29459679}, issn = {1546-1718}, abstract = {Stature is affected by many polymorphisms of small effect in humans 1 . In contrast, variation in dogs, even within breeds, has been suggested to be largely due to variants in a small number of genes2,3. Here we use data from cattle to compare the genetic architecture of stature to those in humans and dogs. We conducted a meta-analysis for stature using 58,265 cattle from 17 populations with 25.4 million imputed whole-genome sequence variants. Results showed that the genetic architecture of stature in cattle is similar to that in humans, as the lead variants in 163 significantly associated genomic regions (P < 5 × 10-8) explained at most 13.8% of the phenotypic variance. Most of these variants were noncoding, including variants that were also expression quantitative trait loci (eQTLs) and in ChIP-seq peaks. There was significant overlap in loci for stature with humans and dogs, suggesting that a set of common genes regulates body size in mammals.}, } @article {pmid29459678, year = {2018}, author = {Rošić, S and Amouroux, R and Requena, CE and Gomes, A and Emperle, M and Beltran, T and Rane, JK and Linnett, S and Selkirk, ME and Schiffer, PH and Bancroft, AJ and Grencis, RK and Jeltsch, A and Hajkova, P and Sarkies, P}, title = {Evolutionary analysis indicates that DNA alkylation damage is a byproduct of cytosine DNA methyltransferase activity.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {452-459}, pmid = {29459678}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; 322790//European Research Council/International ; MC_U120092689//Medical Research Council/United Kingdom ; MC_UP_1102/13//Medical Research Council/United Kingdom ; }, abstract = {Methylation at the 5 position of cytosine in DNA (5meC) is a key epigenetic mark in eukaryotes. Once introduced, 5meC can be maintained through DNA replication by the activity of 'maintenance' DNA methyltransferases (DNMTs). Despite their ancient origin, DNA methylation pathways differ widely across animals, such that 5meC is either confined to transcribed genes or lost altogether in several lineages. We used comparative epigenomics to investigate the evolution of DNA methylation. Although the model nematode Caenorhabditis elegans lacks DNA methylation, more basal nematodes retain cytosine DNA methylation, which is targeted to repeat loci. We found that DNA methylation coevolved with the DNA alkylation repair enzyme ALKB2 across eukaryotes. In addition, we found that DNMTs introduced the toxic lesion 3-methylcytosine into DNA both in vitro and in vivo. Alkylation damage is therefore intrinsically associated with DNMT activity, and this may promote the loss of DNA methylation in many species.}, } @article {pmid29459677, year = {2018}, author = {Breslow, DK and Hoogendoorn, S and Kopp, AR and Morgens, DW and Vu, BK and Kennedy, MC and Han, K and Li, A and Hess, GT and Bassik, MC and Chen, JK and Nachury, MV}, title = {A CRISPR-based screen for Hedgehog signaling provides insights into ciliary function and ciliopathies.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {460-471}, pmid = {29459677}, issn = {1546-1718}, support = {R00 HD082280/HD/NICHD NIH HHS/United States ; K99 HD082280/HD/NICHD NIH HHS/United States ; P50 GM107615/GM/NIGMS NIH HHS/United States ; S10 RR022448/RR/NCRR NIH HHS/United States ; R01 GM113100/GM/NIGMS NIH HHS/United States ; T32 HG000044/HG/NHGRI NIH HHS/United States ; S10 RR027425/RR/NCRR NIH HHS/United States ; P30 CA124435/CA/NCI NIH HHS/United States ; R01 GM089933/GM/NIGMS NIH HHS/United States ; S10 RR025518/RR/NCRR NIH HHS/United States ; }, abstract = {Primary cilia organize Hedgehog signaling and shape embryonic development, and their dysregulation is the unifying cause of ciliopathies. We conducted a functional genomic screen for Hedgehog signaling by engineering antibiotic-based selection of Hedgehog-responsive cells and applying genome-wide CRISPR-mediated gene disruption. The screen can robustly identify factors required for ciliary signaling with few false positives or false negatives. Characterization of hit genes uncovered novel components of several ciliary structures, including a protein complex that contains δ-tubulin and ε-tubulin and is required for centriole maintenance. The screen also provides an unbiased tool for classifying ciliopathies and showed that many congenital heart disorders are caused by loss of ciliary signaling. Collectively, our study enables a systematic analysis of ciliary function and of ciliopathies, and also defines a versatile platform for dissecting signaling pathways through CRISPR-based screening.}, } @article {pmid29459288, year = {2018}, author = {Bi, S and Sourjik, V}, title = {Stimulus sensing and signal processing in bacterial chemotaxis.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {22-29}, doi = {10.1016/j.mib.2018.02.002}, pmid = {29459288}, issn = {1879-0364}, abstract = {Motile bacteria use chemotaxis to migrate towards environments that are favorable for growth and survival. The signaling pathway that mediates this behavior is largely conserved among prokaryotes, with Escherichia coli chemotaxis system being one of the simplest and the best studied. At the core of this pathway are the arrays of clustered chemoreceptors that detect, amplify and integrate various stimuli. Recent work provided deeper understanding of spatial organization and signal processing by these clusters and uncovered the variety of sensory mechanisms used to detect environmental stimuli. Moreover, studies of bacteria with different lifestyles have led to new insights into the diversity and evolutionary conservation of the chemotaxis pathway, as well as the physiological relevance of chemotactic behavior in different environments.}, } @article {pmid29458978, year = {2018}, author = {Prassack, KA and Pante, MC and Njau, JK and de la Torre, I}, title = {The paleoecology of Pleistocene birds from Middle Bed II, at Olduvai Gorge, Tanzania, and the environmental context of the Oldowan-Acheulean transition.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {32-47}, doi = {10.1016/j.jhevol.2017.11.003}, pmid = {29458978}, issn = {1095-8606}, abstract = {Fossil bird data (community composition and taphonomic profiles) are used here to infer the environmental context of the Oldowan-Acheulean transitional period at Olduvai Gorge, Tanzania. This is the first comprehensive report on the Middle Bed II avifauna and includes fossils excavated by the Olduvai Geochronology and Archaeology Project (OGAP) and recently rediscovered fossils collected by Mary Leakey. Crane, ibis, darter, owl, raptor, crow, and vulture are reported from Bed II for the first time. The presence of these taxa, absent earlier in this Bed, point to a general opening and drying of the landscape with grassland and open woodland expansion. Taxa associated with dense, emergent wetland vegetation, such as dabbling ducks and rails, are uncommon and less diverse than earlier in Bed II. This suggests more mature wetlands with clearer waters. Cormorants continue to be common, but are less diverse. Cormorants and other roosting taxa provide evidence of trees in the area. Compared to lowermost Bed II, the Middle to Upper Bed II landscape is interpreted here as more open and drier (but not necessarily more arid), with matured wetlands, scattered trees, and a greater expansion of grasslands.}, } @article {pmid29458950, year = {2018}, author = {Lange, M}, title = {A reply to Craver and Povich on the directionality of distinctively mathematical explanations.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {85-88}, doi = {10.1016/j.shpsa.2018.01.002}, pmid = {29458950}, issn = {0039-3681}, } @article {pmid29458949, year = {2018}, author = {MacLeod, M and Nagatsu, M}, title = {What does interdisciplinarity look like in practice: Mapping interdisciplinarity and its limits in the environmental sciences.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {74-84}, doi = {10.1016/j.shpsa.2018.01.001}, pmid = {29458949}, issn = {0039-3681}, abstract = {In this paper we take a close look at current interdisciplinary modeling practices in the environmental sciences, and suggest that closer attention needs to be paid to the nature of scientific practices when investigating and planning interdisciplinarity. While interdisciplinarity is often portrayed as a medium of novel and transformative methodological work, current modeling strategies in the environmental sciences are conservative, avoiding methodological conflict, while confining interdisciplinary interactions to a relatively small set of pre-existing modeling frameworks and strategies (a process we call crystallization). We argue that such practices can be rationalized as responses in part to cognitive constraints which restrict interdisciplinary work. We identify four salient integrative modeling strategies in environmental sciences, and argue that this crystallization, while contradicting somewhat the novel goals many have for interdisciplinarity, makes sense when considered in the light of common disciplinary practices and cognitive constraints. These results provide cause to rethink in more concrete methodological terms what interdisciplinarity amounts to, and what kinds of interdisciplinarity are obtainable in the environmental sciences and elsewhere.}, } @article {pmid29458948, year = {2018}, author = {Raffo Quintana, F}, title = {Leibniz on the requisites of an exact arithmetical quadrature.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {65-73}, doi = {10.1016/j.shpsa.2017.12.003}, pmid = {29458948}, issn = {0039-3681}, abstract = {In this paper we will try to explain how Leibniz justified the idea of an exact arithmetical quadrature. We will do this by comparing Leibniz's exposition with that of John Wallis. In short, we will show that the idea of exactitude in matters of quadratures relies on two fundamental requisites that, according to Leibniz, the infinite series have, namely, that of regularity and that of completeness. In the first part of this paper, we will go deeper into three main features of Leibniz's method, that is: it is an infinitesimal method, it looks for an arithmetical quadrature and it proposes a result that is not approximate, but exact. After that, we will deal with the requisite of the regularity of the series, pointing out that, unlike the inductive method proposed by Wallis, Leibniz propounded some sort of intellectual recognition of what is invariant in the series. Finally, we will consider the requisite of completeness of the series. We will see that, although both Wallis and Leibniz introduced the supposition of completeness, the German thinker went beyond the English mathematician, since he recognized that it is not necessary to look for a number for the quadrature of the circle, given that we have a series that is equal to the area of that curvilinear figure.}, } @article {pmid29458947, year = {2018}, author = {Schindler, S}, title = {A coherentist conception of ad hoc hypotheses.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {54-64}, doi = {10.1016/j.shpsa.2017.11.011}, pmid = {29458947}, issn = {0039-3681}, abstract = {What does it mean for a hypothesis to be ad hoc? One prominent account has it that ad hoc hypotheses have no independent empirical support. Others have viewed ad hoc judgements as stemming from a lack of unifiedness of the amended theory. Still others view them as merely subjective. Here I critically review these views and defend my own Coherentist Conception of Ad hocness by working out its conceptual and descriptive attractions.}, } @article {pmid29458946, year = {2018}, author = {Campos, DG}, title = {Heuristic analogy in Ars Conjectandi: From Archimedes' De Circuli Dimensione to Bernoulli's theorem.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {44-53}, doi = {10.1016/j.shpsa.2017.12.002}, pmid = {29458946}, issn = {0039-3681}, abstract = {This article investigates the way in which Jacob Bernoulli proved the main mathematical theorem that undergirds his art of conjecturing-the theorem that founded, historically, the field of mathematical probability. It aims to contribute a perspective into the question of problem-solving methods in mathematics while also contributing to the comprehension of the historical development of mathematical probability. It argues that Bernoulli proved his theorem by a process of mathematical experimentation in which the central heuristic strategy was analogy. In this context, the analogy functioned as an experimental hypothesis. The article expounds, first, Bernoulli's reasoning for proving his theorem, describing it as a process of experimentation in which hypothesis-making is crucial. Next, it investigates the analogy between his reasoning and Archimedes' approximation of the value of π, by clarifying both Archimedes' own experimental approach to the said approximation and its heuristic influence on Bernoulli's problem-solving strategy. The discussion includes some general considerations about analogy as a heuristic technique to make experimental hypotheses in mathematics.}, } @article {pmid29458945, year = {2018}, author = {Vasudevan, A}, title = {Chance, determinism and the classical theory of probability.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {32-43}, doi = {10.1016/j.shpsa.2017.11.009}, pmid = {29458945}, issn = {0039-3681}, abstract = {This paper situates the metaphysical antinomy between chance and determinism in the historical context of some of the earliest developments in the mathematical theory of probability. Since Hacking's seminal work on the subject, it has been a widely held view that the classical theorists of probability were guilty of an unwitting equivocation between a subjective, or epistemic, interpretation of probability, on the one hand, and an objective, or statistical, interpretation, on the other. While there is some truth to this account, I argue that the tension at the heart of the classical theory of probability is not best understood in terms of the duality between subjective and objective interpretations of probability. Rather, the apparent paradox of chance and determinism, when viewed through the lens of the classical theory of probability, manifests itself in a much deeper ambivalence on the part of the classical probabilists as to the rational commensurability of causal and probabilistic reasoning.}, } @article {pmid29458944, year = {2018}, author = {Dawes, GW and Smith, T}, title = {The naturalism of the sciences.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {22-31}, doi = {10.1016/j.shpsa.2017.11.012}, pmid = {29458944}, issn = {0039-3681}, abstract = {The sciences are characterized by what is sometimes called a "methodological naturalism," which disregards talk of divine agency. In response to those who argue that this reflects a dogmatic materialism, a number of philosophers have offered a pragmatic defense. The naturalism of the sciences, they argue, is provisional and defeasible: it is justified by the fact that unsuccessful theistic explanations have been superseded by successful natural ones. But this defense is inconsistent with the history of the sciences. The sciences have always exhibited what we call a domain naturalism. They have never invoked divine agency, but have always focused on the causal structure of the natural world. It is not the case, therefore, that the sciences once employed theistic explanations and then abandoned them. The naturalism of the sciences is as old as science itself.}, } @article {pmid29458943, year = {2018}, author = {Baldissera Pacchetti, M}, title = {A role for spatiotemporal scales in modeling.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {14-21}, doi = {10.1016/j.shpsa.2017.10.006}, pmid = {29458943}, issn = {0039-3681}, abstract = {Bogen and Woodward's distinction between data and phenomena raises the need to understand the structure of the data-to-phenomena and theory-to-phenomena inferences. I suggest that one way to study the structure of these inferences is to analyze the role of the assumptions involved in the inferences: What kind of assumptions are they? How do these assumptions contribute to the practice of identifying phenomena? In this paper, using examples from atmospheric dynamics, I develop an account of the practice of identifying the target in the data-to-phenomena and theory-to-phenomena inferences in which assumptions about spatiotemporal scales play a central role in the identification of parameters that describe the target system. I also argue that these assumptions are not only empirical but they are also idealizing and abstracting. I conclude the paper with a reflection on the role of idealizations in modeling.}, } @article {pmid29458942, year = {2018}, author = {Rossetter, T}, title = {Realism on the rocks: Novel success and James Hutton's theory of the earth.}, journal = {Studies in history and philosophy of science}, volume = {67}, number = {}, pages = {1-13}, doi = {10.1016/j.shpsa.2017.10.005}, pmid = {29458942}, issn = {0039-3681}, abstract = {In this paper, I introduce a new historical case study into the scientific realism debate. During the late-eighteenth century, the Scottish natural philosopher James Hutton made two important successful novel predictions. The first concerned granitic veins intruding from granite masses into strata. The second concerned what geologists now term "angular unconformities": older sections of strata overlain by younger sections, the two resting at different angles, the former typically more inclined than the latter. These predictions, I argue, are potentially problematic for selective scientific realism in that constituents of Hutton's theory that would not be considered even approximately true today played various roles in generating them. The aim here is not to provide a full philosophical analysis but to introduce the case into the debate by detailing the history and showing why, at least prima facie, it presents a problem for selective realism. First, I explicate Hutton's theory. I then give an account of Hutton's predictions and their confirmations. Next, I explain why these predictions are relevant to the realism debate. Finally, I consider which constituents of Hutton's theory are, according to current beliefs, true (or approximately true), which are not (even approximately) true, and which were responsible for these successes.}, } @article {pmid29458682, year = {2018}, author = {Nouioui, I and Ghodhbane-Gtari, F and Klenk, HP and Gtari, M}, title = {Frankia saprophytica sp. nov., an atypical, non-infective (Nod-) and non-nitrogen fixing (Fix-) actinobacterium isolated from Coriaria nepalensis root nodules.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1090-1095}, doi = {10.1099/ijsem.0.002633}, pmid = {29458682}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Frankia/*classification/genetics/isolation & purification ; Magnoliopsida/*microbiology ; Nucleic Acid Hybridization ; Pakistan ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain CN3T, a Coriaria nepalensis isolate, appears to form hyphae and sporangia typical of members fo the genus Frankia. However, it failed to form vesicles, to reduce acetylene and to induce nodules on its original host plant. A polyphasic approach was used here to determine the taxonomic status of strain CN3T. The 16S rRNA gene sequence of strain CN3T showed the highest sequence identity with Frankia asymbiotica type strain M16386T (99.4 %). Digital DNA-DNA hybridization between strains CN3T and M16386T was 25.7 %, which is clearly below the accepted cut-off point of 70 %. The G+C content of DNA was 71.8 mol%. Whole-cell hydrolysates of strain CN3T were rich in meso-diaminopimelic acid. Cell-wall sugars were composed of galactose, glucose, mannose, rhamnose and traces of ribose. The polar lipid profile contained phosphatidylinositol, phosphatidylglycerol, diphosphatidylglycerol, phosphoglycolipids, phospholipid, six uncharacterized glycolipids and two uncharacterized lipids. The predominant menaquinone (>25 %) was MK-9(H6). Major fatty acids (>15 %) of strain CN3T consisted of iso-C16 : 0, C17 : 1ω8c and C15 : 0. Based on 16S rRNA gene phylogeny, genome sequence analysis and phenotypic results, strain CN3T (=DSM 105290T=CECT 9314T) is proposed to represent the type strain of a novel species, Frankia saprophytica sp. nov.}, } @article {pmid29458677, year = {2018}, author = {Amano, N and Yamamuro, A and Miyahara, M and Kouzuma, A and Abe, T and Watanabe, K}, title = {Methylomusa anaerophila gen. nov., sp. nov., an anaerobic methanol-utilizing bacterium isolated from a microbial fuel cell.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1118-1122}, doi = {10.1099/ijsem.0.002635}, pmid = {29458677}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; *Bioelectric Energy Sources ; Bioreactors ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Firmicutes/*classification/genetics/isolation & purification ; Japan ; Methanol ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/microbiology ; }, abstract = {Abacterial strain, designated MMFC1T, was isolated from a methanol-fed microbial fuel cell that had been inoculated with sludge obtained from a wastewater-treatmentfacility in a chemical plant. The strain grows by fermenting methanol to produce acetate under anaerobic conditions, while homoacetogenic growth is not observed. MMFC1T also grows on pyruvate and lactate but not on sugars and other organic acids. Cells are curved rods and motile, have peritrichous flagella, and form endospores. The genome sequence of strain MMFC1T supports the physiological data. Phylogenetic analysis based on the 16S rRNA gene sequence shows that strain MMFC1T is affiliated with the family Sporomusaceae, while the closest relative is Sporomusa ovata with nucleotide-sequencesimilarity of 93.5 %. Major fatty acids are iso-C13 : 0 3-OH, C16 : 1ω9 and iso-C17 : 0. On the basis of its physiological, genomic and phylogenetic features, a novel genus and species are proposed to accommodate strain MMFC1T, with the name Methylomusa anaerophila gen. nov., sp. nov. The type strain of Methylomusa anaerophila is MMFC1T (=JCM 31821T = KCTC 15592T).}, } @article {pmid29458671, year = {2018}, author = {Pascual, J and Foesel, BU and Geppert, A and Huber, KJ and Boedeker, C and Luckner, M and Wanner, G and Overmann, J}, title = {Roseisolibacter agri gen. nov., sp. nov., a novel slow-growing member of the under-represented phylum Gemmatimonadetes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1028-1036}, doi = {10.1099/ijsem.0.002619}, pmid = {29458671}, issn = {1466-5034}, mesh = {Agriculture ; Bacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Electron Transport Complex IV/genetics ; Fatty Acids/chemistry ; Namibia ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel slow-growing bacterium, designated strain AW1220T, was isolated from agricultural floodplain soil sampled at Mashare (Kavango region, Namibia) by using a high-throughput cultivation approach. Strain AW1220T was characterized as a Gram-negative, non-motile, rod-shaped bacterium. Occasionally, some cells attained an unusual length of up to 35 µm. The strain showed positive responses for catalase and cytochrome-c oxidase and divided by binary fission and/or budding. The strain had an aerobic chemoorganoheterotrophic metabolism and was also able to grow under micro-oxic conditions. Colonies were small and pink pigmented. Strain AW1220T was found to be a mesophilic, neutrophilic and non-halophilic bacterium. Cells accumulated polyphosphate intracellularly and mainly utilized complex protein substrates for growth. 16S rRNA gene sequence comparisons revealed that strain AW1220T belonged to the class Gemmatimonadetes (=group 1). Its closest relatives were found to be Gemmatimonas aurantiaca T-27T (90.9 % gene sequence similarity), Gemmatimonas phototrophica AP64T (90.8 %) and Longimicrobiumterrae CB-286315T (84.2 %). The genomic G+C content was 73.3 mol%. The major fatty acids were iso-C15 : 0, C16 : 1ω7c and/or iso-C15 : 0 2-OH, iso-C17 : 1ω9c, iso-C15 : 0 3-OH and C16 : 0. The predominant respiratory quinone was MK-9, albeit minor amounts of MK-8 and MK-10 are also present. The polar lipids comprised major amounts of phosphatidylethanolamine, phosphatidylcholine, diphosphatidylglycerol and one unidentified phosphoglycolipid. On the basis of its polyphasic characterization, strain AW1220T represents a novel genus and species of the class Gemmatimonadetes for which the name Roseisolibacter agri gen. nov., sp. nov. is proposed, with the type strain AW1220T (=DSM 104292T=LMG 29977T).}, } @article {pmid29458669, year = {2018}, author = {Barcytė, D and Hodač, L and Nedbalová, L and Elster, J}, title = {Chloromonas arctica sp. nov., a psychrotolerant alga from snow in the High Arctic (Chlamydomonadales, Chlorophyta).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {851-859}, doi = {10.1099/ijsem.0.002595}, pmid = {29458669}, issn = {1466-5034}, mesh = {DNA, Algal/genetics ; DNA, Ribosomal Spacer/genetics ; *Phylogeny ; Plastids/genetics ; RNA, Ribosomal, 18S/genetics ; Sequence Analysis, DNA ; *Snow ; Svalbard ; Volvocida/*classification/genetics ; }, abstract = {With the advent of molecular phylogenetic methods, it has become possible to assess the bioversity of snow algae more accurately. In this study, we focused on a morphological, ultrastructural and taxonomic description of a new Chloromonas-like alga isolated from snow in the High Arctic (Svalbard). Light and transmission electron microscopy revealed broad ellipsoidal or ellipsoidal-cylindrical, occasionally spherical cells with a chloroplast without a pyrenoid, an inconspicuous eyespot and a papilla. The size difference and the aforementioned morphological traits clearly distinguished the alga from its closest counterparts within the genus Chloromonas. Moreover, we were able to cultivate the alga at both 5 and 20 °C, revealing the psychrotolerant nature of the strain. Phylogenetic analyses of the plastid rbcL and nuclear 18S rRNA gene showed that the alga is nested within a clade containing a number of psychrotolerant strains within the Chloromonadinia phylogroup (Chlorophyceae). In the rbcL phylogeny, the alga formed an independent lineage, sister to the freshwater species Chloromonas paraserbinowii. Comparisons of secondary structure models of a highly variable ITS2 rDNA marker showed support for a distinct species identity for the new strain. The ITS2 secondary structure of the new isolate differed from the closest matches 'Chlamydomonas' gerloffii and Choloromonas reticulata by three and five compensatory base changes, respectively. Considering the morphological and molecular differences from its closest relatives, a new psychrotolerant species from the Arctic, Choromonas arctica sp. nov., is proposed.}, } @article {pmid29458666, year = {2018}, author = {Yang, ZW and Salam, N and Asem, MD and Fang, BZ and Lan, L and Xiao, M and Wadaan, MAM and Hozzein, WN and Li, WJ}, title = {Saccharopolyspora deserti sp. nov., a novel halotolerant actinobacterium isolated from a desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {860-864}, doi = {10.1099/ijsem.0.002598}, pmid = {29458666}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Desert Climate ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Saccharopolyspora/*classification/genetics/isolation & purification ; *Salinity ; Saudi Arabia ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain SYSU D8010T was isolated from a desert sand sample collected in Saudi Arabia. The taxonomic position of the isolate was investigated by the polyphasic taxonomic approach. The isolate was found to be Gram-positive and aerobic. The strain was able to grow at 14-40 °C, pH 5.0-9.0 and in the presence of up to 22 % (w/v) NaCl. Strain SYSU D8010T contained meso-diaminopimelic acid as cell-wall diamino acid, and arabinose, fucose, galactose, glucose and rhamnose as the whole-cell sugars. The primary polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, phosphatidylinositol and phosphatidylinositolmannosides. Menaquinone MK-9(H4) was detected as the respiratory quinone; and anteiso-C17 : 0, iso-C16 : 0, iso-C15 : 0 and iso-C17 : 0 as the predominant fatty acids. Pairwise comparison of the 16S rRNA gene sequences indicated that strain SYSU D8010T had a sequence similarity of 97.8 % to Saccharopolyspora halophila YIM 90500T. The genomic DNA G+C content of strain SYSU D8010T was determined to be 69.9 mol%. Based on the analyses of the phenotypic, genotypic and phylogenetic characteristics, strain SYSU D8010T was determined to represent a novel species of the genus Saccharopolyspora, for which the name Saccharopolyspora deserti sp. nov. is proposed. The type strain of the species is SYSU D8010T (=KCTC 39989T=CPCC 204620T).}, } @article {pmid29458662, year = {2018}, author = {Li, W and Ten, LN and Lee, SY and Kang, IK and Jung, HY}, title = {Spirosoma horti sp. nov., isolated from apple orchard soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {930-935}, doi = {10.1099/ijsem.0.002614}, pmid = {29458662}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; *Farms ; Fatty Acids/chemistry ; *Malus ; Phosphatidylethanolamines/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-negative, motile by gliding, rod-shaped, aerobic bacterium, designated S7-3-19T, was isolated from apple orchard soil in Gyeongsangnam-do Province, Republic of Korea, and characterized taxonomically by using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequencing showed that strain S7-3-19T belonged to the family Cytophagaceae and was most closely related to Spirosoma linguale DSM 74T (96.38 %), Spirosoma fluviale MSd3T (96.38 %), Spirosoma pulveris JSH5-14T (96.35 %) and Spirosoma radiotolerans DG5AT (96.24 %). Chemotaxonomic characteristics supported the classification of strain S7-3-19T within the genus Spirosoma. Summed feature 3 (C16 : 1ω7c/C16 : 1ω6c; 46.7 %) and C16 : 1ω5c (23.8 %) were the major fatty acids. Phosphatidylethanolamine, an unidentified aminophospholipid, an unidentified phospholipid and two unidentified lipids were the major polar lipids. Menaquinone with seven isoprene units was the predominant respiratory quinone. The G+C content of the genomic DNA of strain S7-3-19T was 48.6 mol%. On the basis of its phenotypic properties, genotypic distinctiveness and chemotaxonomic features, strain S7-3-19T represents a novel species of the genus Spirosoma, for which the name Spirosomahorti sp. nov. is proposed. The type strain is S7-3-19T (=KCTC 52728T=JCM 32131T).}, } @article {pmid29458658, year = {2018}, author = {Gan, L and Long, X and Zhang, H and Hou, Y and Tian, J and Zhang, Y and Tian, Y}, title = {Halomonas saliphila sp. nov., a moderately halophilic bacterium isolated from a saline soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1153-1159}, doi = {10.1099/ijsem.0.002644}, pmid = {29458658}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Halomonas/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel, Gram-stain-negative, aerobic, rod-shaped, motile and moderately halophilic bacterium, designated strain LCB169T, was isolated from a saline soil sample from Gansu Province, PR China. The cells of LCB169T grew at 10-52 °C (optimum 30 °C), at pH 6.0-10.0 (optimum pH 8.0) and in the presence of 0-17 % (w/v) NaCl (optimum 10-15 %). Phylogenetic analysis based on 16S rRNA gene sequences and concatenated 16S rRNA, gyrB and rpoD genes sequences revealed that LCB169T represented a member of the genus Halomonas in the class Gammaproteobacteria. The most closely related species were Halomonas daqingensis DQD2-30T (98.0 % 16S rRNA gene sequence similarity), Halomonas kenyensis AIR-2T (97.8 %) and Halomonas desiderata FB2T (97.5 %). DNA-DNA relatedness values between LCB169T and H. daqingensis CGMCC 1.6443T, H. desiderata DSM 9502T and H. kenyensis DSM 17331T were 33, 35 and 38 %, respectively. The polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine and three unidentified phospholipids. The major fatty acids were C18 : 1ω7c, C16 : 0, C16 : 1ω7c and C12 : 0 3-OH. The genomic DNA G+C content was 66.1 mol% and the predominant respiratory quinone was Q-9. On the basis of the results of phenotypic, phylogenetic and chemotaxonomic analyses and DNA-DNA hybridization relatedness values, LCB169T is considered to represent a novel species of the genus Halomonas, for which the name Halomonas saliphila sp. nov. is proposed. The type strain is LCB169T (=CGMCC 1.15818T=KCTC 52618T).}, } @article {pmid29458566, year = {2018}, author = {Kim, YS and Cha, CJ}, title = {Paenibacillus translucens sp. nov., isolated from tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {936-941}, doi = {10.1099/ijsem.0.002613}, pmid = {29458566}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Glycolipids/chemistry ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-variable, aerobic, rod-shaped, motile and spore-forming bacterial strain, designated CJ11T, was isolated from a tidal flat sediment sample from Ganghwa-do, Republic of Korea. Strain CJ11T grew optimally on R2A at 30 °C and pH 7.0. Sequencing results of the 16S rRNA gene revealed that strain CJ11T possesses two copies of the 16S rRNA gene varying at five nucleotide positions. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CJ11T belonged to the genus Paenibacillus within the family Paenibacillaceae and was most closely related to Paenibacillus lacus KCTC 33691T (99.36-99.15 % similarity). DNA-DNA relatedness levels of strain CJ11T was 41.7 % (reciprocal, 57.8 %) to P. lacus KCTC 33691T. The G+C content of the genomic DNA was 51.0 mol%. Strain CJ11Tcontained meso-diaminopimelic acid in the cell-wall peptidoglycan. The major isoprenoid quinone was menaquinone-7. The major cellular fatty acids were anteiso-C15 : 0, C16 : 0 and iso-C16 : 0. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, two unidentified phospholipids, an unidentified glycolipid and several unidentified lipids. On the basis of the polyphasic taxonomic study, strain CJ11T represents a novel species in the genus Paenibacillus, for which the name Paenibacillustranslucens sp. nov. is proposed. The type strain is CJ11T (=KACC 19304T=JCM 32080T).}, } @article {pmid29458564, year = {2018}, author = {Mashima, I and Liao, YC and Miyakawa, H and Theodorea, CF and Thawboon, B and Thaweboon, S and Scannapieco, FA and Nakazawa, F}, title = {Veillonella infantium sp. nov., an anaerobic, Gram-stain-negative coccus isolated from tongue biofilm of a Thai child.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1101-1106}, doi = {10.1099/ijsem.0.002632}, pmid = {29458564}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; *Biofilms ; Child ; DNA, Bacterial/genetics ; Genes, Bacterial ; Humans ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Thailand ; Tongue/*microbiology ; Veillonella/*classification/genetics/isolation & purification ; }, abstract = {A strain of a novel anaerobic, Gram-stain-negative coccus was isolated from the tongue biofilm of a Thai child. This strain was shown, at the phenotypic level and based on 16S rRNA gene sequencing, to be a member of the genus Veillonella. Comparative analysis of the 16S rRNA, dnaK and rpoB gene sequences indicated that phylogenetically the strain comprised a distinct novel branch within the genus Veillonella. The novel strain showed 99.8, 95.1 and 95.9 % similarity to partial 16S rRNA, dnaK and rpoB gene sequences, respectively, to the type strains of the two most closely related species, Veillonelladispar ATCC 17748T and Veillonellatobetsuensis ATCC BAA-2400T. The novel strain could be discriminated from previously reported species of the genus Veillonella based on partial dnaK and rpoB gene sequencing and average nucleotide identity values. The major acid end-product produced by this strain was acetic acid under anaerobic conditions in trypticase-yeast extract-haemin with 1 % (w/v) glucose or fructose medium. Lactate was fermented to acetic acid and propionic acid. Based on these observations, this strain represents a novel species, for which the name Veillonella infantium sp. nov. is proposed. The type strain is T11011-4T (=JCM 31738T=TSD-88T).}, } @article {pmid29458563, year = {2018}, author = {Hirota, K and Nishita, M and Tu, Z and Matsuyama, H and Yumoto, I}, title = {Bacillus fermenti sp. nov., an indigo-reducing obligate alkaliphile isolated from indigo fermentation liquor for dyeing.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1123-1129}, doi = {10.1099/ijsem.0.002636}, pmid = {29458563}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; *Coloring Agents ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Fermentation ; Indigo Carmine/analysis ; Japan ; Nucleic Acid Hybridization ; *Phylogeny ; Polygonum/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {The indigo-reducing, facultatively anaerobic and obligately alkaliphilic strains Bf-1T, Bf-2 and Bf-4 were isolated from an indigo fermentation liquor used for dyeing, which uses sukumo [composted Polygonum indigo (Polygonum tinctorium Lour.) leaves] as a basic ingredient and was obtained from a craft centre in Date City, Hokkaido, Japan. The 16S rRNA gene sequence analyses indicated that the closest neighbours of strain Bf-1T are Bacillus maritimus DSM 100413T (98.3 % 16S rRNA gene sequence similarity), Bacillus persicus DSM 25386T (98.2 %) and Bacillus rigiliprofundi LMG 28275T (97.7 %). The 16S rRNA gene sequence of strain Bf-1T was almost identical to the sequences of strains Bf-2 and Bf-4 (99.9 %). Cells of strain Bf-1T stained Gram-positive and formed straight rods that achieved motility through a pair of subpolar flagella. Strain Bf-1T grew at temperatures of between 15 and 45 °C with optimum growth at 33‒40 °C. The strain grew in the pH range of pH 8‒12, with optimum growth at pH 10. The isoprenoid quinone detected was menaquinone-7 (MK-7), and the DNA G+C content was 41.7 %. The whole-cell fatty acid profile mainly (>10 %) consisted of iso-C15 : 0 and iso-C16 : 0. Phylogenetically related neighbours, although demonstrating high 16S rRNA gene sequence similarity (>97.6 %) with strain Bf-1T, exhibited less than 9 % relatedness in DNA-DNA hybridization experiments. Based on evidence from this polyphasic study, the isolates represent a novel species, for which the name Bacillus fermenti sp. nov. is proposed. The type strain of this species is Bf-1T (=JCM 31807T=NCIMB 15079T).}, } @article {pmid29458549, year = {2018}, author = {Tak, EJ and Kim, HS and Lee, JY and Kang, W and Hyun, DW and Kim, PS and Shin, NR and Bae, JW}, title = {Tessaracoccus aquimaris sp. nov., isolated from the intestine of a Korean rockfish, Sebastes schlegelii, from a marine aquaculture pond.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1065-1072}, doi = {10.1099/ijsem.0.002626}, pmid = {29458549}, issn = {1466-5034}, mesh = {Animals ; Aquaculture ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Intestines/*microbiology ; Perciformes/*microbiology ; *Phylogeny ; Ponds ; Propionibacteriaceae/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel coccus-shaped, Gram-stain-positive, non-motile and aerobic bacterium, designated strain NSG39T, was isolated from the intestine of a Korean rockfish, Sebastes schlegelii. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the newly isolated strain NSG39T was closely related to Tessaracoccus flavus RP1T (98.0 %). The isolate grew at 15-37 °C, pH 7-9 and 0-4 % (w/v) salinity, with optimal growth at 30 °C, pH 8 and 0 % (w/v) salinity. The cell wall of the organism contained ll-diaminopimelic acid as a diagnostic diamino acid, and ribose, mannose, glucose and galactose as diagnostic sugars. The polar lipid comprised diphosphatidylglycerol, phosphatidylglycerol, three glycolipids and four unidentified polar lipids. The major cellular fatty acid was anteiso-C15 : 0 (47.2 %). The major menaquinone was MK-9 (H4). The DNA G+C content of the isolate was 68.8 mol%. The genome-based orthologous average nucleotide identity value for strain NSG39T and T. flavus RP1T was 76.6 %. Based on the phylogenetic analysis and its biological characteristics, strain NSG39T is considered to represent a novel species of the genus Tessaracoccus, for which the name Tessaracoccus aquimaris is proposed. The type strain is NSG39T (=KACC 17540T=JCM 19289T).}, } @article {pmid29458546, year = {2018}, author = {Cui, MD and Wang, X and Jiang, WK and Hu, G and Yang, ZG and Sun, GJ and Zhu, SJ and Zhou, YD and Hong, Q}, title = {Pedobacter agrisoli sp. nov., isolated from farmland soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {886-891}, doi = {10.1099/ijsem.0.002604}, pmid = {29458546}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; *Farms ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Pedobacter/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Spermidine/analogs & derivatives/chemistry ; Vitamin K 2/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile, non-spore-forming and rod-shaped bacterium, designated YHM-9T, was isolated from soil in Yangquan, Shanxi Province, PR China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain YHM-9T belonged to the genus Pedobacter and shared the highest similarity (97.4 %) to the type strain Pedobacter lignilitoris W-WS13T. Strain YHM-9T exhibited low DNA-DNA relatedness with P. lignilitoris W-WS13T (21.7±1.3 %). The DNA G+C content was 38.9 mol%. The major fatty acids were iso-C15 : 0, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and iso-C17 : 0 3-OH. The respiratory quinone was MK-7, the major polyamine was sym-homospermidine and the major polar lipids were phosphatidylethanolamine. Based on the morphological, physiological, biochemical and chemotaxonomic characteristics, strain YHM-9T was recognized as a representative of a novel species within the genus Pedobacter, for which the name Pedobacteragrisoli sp. nov. is proposed. The type strain is YHM-9T (=JCM 32093T=CCTCC AB 2017125T).}, } @article {pmid29458543, year = {2018}, author = {Sun, J and Xing, M and Wang, W and Dai, F and Liu, J and Hao, J}, title = {Hymenobacter profundi sp. nov., isolated from deep-sea water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002621}, pmid = {29458543}, issn = {1466-5034}, abstract = {A Gram-stain-negative, rod-shaped, red-pigmented, aerobic bacterium, strain M2T, was isolated from a seawater sample collected from the western Pacific Ocean at a depth of 1000 m and characterized using polyphasic taxonomy. Strain M2T was catalase-positive and oxidase-negative. Cells grew at 4-33 °C (optimum, 25 °C), at pH 6-9 (optimum, 7) and with 0-4 % (w/v) (optimum, 1 %) NaCl. Phylogenetic trees based on 16S rRNA gene sequences showed that strain M2T was associated with the genus Hymenobacter. Strain M2T showed the highest 16S rRNA gene sequence similarities to Hymenobacter actinosclerus CCUG 39621T (95.7 %), Hymenobacter tibetensis XTM003T (95.6 %) and Hymenobacter psychrotolerans Tibet-IIU11T (95.2 %). The DNA G+C content was 59.98 mol%. Strain M2T contained C16 : 1ω5c (25.0 %), iso-C15 : 0 (23.9 %) and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c, 20.4 %) as major cellular fatty acids. The major quinone of strain M2T was menaquinone 7 and the major polar lipid was phosphatidylethanolamine. The major polyamine of strain M2T was sym-homospermidine. The phylogenetic analysis and physiological and biochemical data showed that strain M2T should be classified as representing a novel species of the genus Hymenobacter, for which the name Hymenobacter profundi sp. nov. is proposed. The type strain is M2T (=CCTCC AB 2017185T=KCTC 62120T).}, } @article {pmid29458542, year = {2018}, author = {Sun, QL and Yu, C and Luan, ZD and Lian, C and Hu, YH and Sun, L}, title = {Description of Bacillus kexueae sp. nov. and Bacillus manusensis sp. nov., isolated from hydrothermal sediments.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {829-834}, doi = {10.1099/ijsem.0.002594}, pmid = {29458542}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Hydrothermal Vents/*microbiology ; Nucleic Acid Hybridization ; Pacific Ocean ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Two Gram-staining-positive, strictly aerobic bacilli, designated as strains Ma50-5T and Ma50-6T, were isolated from the hydrothermal sediments of Manus Basin in the western Pacific Ocean. Based on 16S rRNA gene sequence, strains Ma50-5T and Ma50-6T were most closely related to Bacillus alveayuensis (97.0 and 97.2 % identity, respectively). The 16S rRNA gene sequence identity between strains Ma50-5T and Ma50-6T was 97.4 %. The identities between strains Ma50-5T and Ma50-6T and other closely related organisms were below 97.0 %. The G+C contents of the genomic DNA of strains Ma50-5T and Ma50-6T were 43.4 and 47.6 mol%, respectively. The major fatty acids (>10 %) of both strains were iso-C15 : 0 and iso-C17 : 0. The predominant isoprenoid quinone detected in both strains was menaquinone-7. Phylogenetic, physiological, biochemical and morphological analyses suggested that strains Ma50-5T and Ma50-6T represent two novel species of the genus Bacillus, for which the names Bacillus kexueae sp. nov. (type strain Ma50-5T=KCTC 33881T=CCTCC AB 2017020T) and Bacillus manusensis sp. nov. (type strain Ma50-6T=KCTC 33882T=CCTCC AB 2017019T), respectively, are proposed.}, } @article {pmid29458537, year = {2018}, author = {Frolov, EN and Zayulina, KS and Kopitsyn, DS and Kublanov, IV and Bonch-Osmolovskaya, EA and Chernyh, NA}, title = {Desulfothermobacter acidiphilus gen. nov., sp. nov., a thermoacidophilic sulfate-reducing bacterium isolated from a terrestrial hot spring.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {871-875}, doi = {10.1099/ijsem.0.002599}, pmid = {29458537}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fermentation ; Firmicutes/*classification/genetics/isolation & purification ; Hot Springs/*microbiology ; Oxidation-Reduction ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Russia ; Sequence Analysis, DNA ; Sulfates/metabolism ; }, abstract = {An anaerobic sulfate-reducing micro-organism, strain 3408-1T, was isolated from a terrestrial hot spring in Kamchatka peninsula (Russia). The cells were spore-forming rods with a Gram-positive type of cell wall. The new isolate was a moderately thermoacidophilic anaerobe able to grow either by sulfate or thiosulfate respiration with H2 or formate as substrates, or by fermenting yeast extract, maltose, sucrose, glucose and pyruvate. The fermentation products were acetate, CO2 and H2. The pH range for growth was 2.9-6.5, with an optimum at 4.5. The temperature range for growth was 42-70 °C, with an optimum at 55 °C. The G+C content of DNA was 58 mol%. Phylogenetic analysis of the 16S rRNA gene showed that strain 3408-1T belongs to the family Thermoanaerobacteraceae, order Thermoanaerobacterales and was distantly related to the species of the genus Ammonifex(93-94 % sequence similarity). On the basis of physiological properties and results of phylogenetic analysis, strain 3408-1T is considered to represent a novel species of a new genus, for which the name Desulfothermobacter acidiphilus gen. nov., sp. nov. is proposed. The type strain is 3408-1T (=DSM 105356T=VKM B-3183T).}, } @article {pmid29458536, year = {2018}, author = {León-Barrios, M and Ramírez-Bahena, MH and Igual, JM and Peix, Á and Velázquez, E}, title = {Phyllobacterium salinisoli sp. nov., isolated from a Lotus lancerottensis root nodule in saline soil from Lanzarote.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1085-1089}, doi = {10.1099/ijsem.0.002628}, pmid = {29458536}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lotus/*microbiology ; Nucleic Acid Hybridization ; Phyllobacteriaceae/*classification/genetics/isolation & purification ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Salinity ; Sequence Analysis, DNA ; *Soil Microbiology ; Spain ; }, abstract = {A Gram-negative rod, designated strain LLAN61T, was isolated from a root nodule of Lotus lancerottensis growing in a saline soil sample from Lanzarote (Canary Islands). The strain grew optimally at 0.5 % (w/v) NaCl and tolerated up to 3.5 %. The 16S rRNA gene sequence analysis showed that strain LLAN61T belonged to genus Phyllobacterium and that Phyllobacteriumleguminum ORS 1419T and Phyllobacteriummyrsinacearum IAM 13584T are the closest related species with 97.93 and 97.86% similarity values, respectively. In the atpD phylogeny, P. leguminum ORS 1419T and P. myrsinacearum ATCC 43591T, sharing similarities of 87.6 and 85.8% respectively, were also the closest species to strain LLAN61T. DNA-DNA hybridization showed an average value of 21 % between strain LLAN61T and P. leguminum LMG 22833T, and 6 % with P. myrsinacearum ATCC 43590T. The predominant fatty acids were C19 : 0 cyclo ω8c and C18 : 1ω6c/C18 : 1ω7c (summed feature 8). The DNA G+C content was 58.0 mol%. Strain LLAN61T differed from its closest relatives in some culture conditions and in assimilation of several carbon sources. Based upon the results of phylogeny, DNA-DNA hybridization, phenotypic tests and fatty acid analysis, this strain should be classified as a novel species of Phyllobacterium for which the name Phyllobacterium salinisoli sp. nov. is proposed (type strain LLAN61T=LMG 30173T = CECT 9417T).}, } @article {pmid29458531, year = {2018}, author = {Kim, DU and Kim, KW and Kang, MS and Kim, JY and Jang, JH and Kim, MK}, title = {Adhaeribacter swui sp. nov., isolated from wet mud.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1096-1100}, doi = {10.1099/ijsem.0.002631}, pmid = {29458531}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain 17mud1-7T, a pink, aerobic, catalase-positive, oxidase-positive and Gram-reaction-negative bacterium, was isolated from wet mud. The isolate grew aerobically at 18-37 °C (optimum 28 °C), at pH 6.0-8.0 (optimum pH 7.0) and in the presence of 0-1 % (w/v) NaCl (optimum 0 % NaCl). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain 17mud1-7T belonged to the genus Adhaeribacter with highest sequence similarity of 96.4 % to Adhaeribacter aerophilus 6424S-25T. The strain showed the typical chemotaxonomic characteristics of the genus Adhaeribacter, with the presence of menaquinone MK-7 as the respiratory quinone, and summed feature 4 (composed of iso-C17 : 1 I/anteiso-C17 : 1 B), iso-C15 : 0 and C16 : 1ω5c as the major fatty acids are. The polar lipid profile contained two aminophosphoglycolipids, two glycolipids and three unidentified lipids. The DNA G+C content of strain 17mud1-7T was 45.9 mol%. Strain 17mud1-7T should thus be classified as representing a novel species in the genus Adhaeribacter, for which the name Adhaeribacter swui sp. nov. is proposed. The type strain is 17mud1-7T (=KCTC 52873T=NBRC 112824T).}, } @article {pmid29458527, year = {2018}, author = {Jiang, WK and Lu, MY and Cui, MD and Wang, X and Wang, H and Yang, ZG and Zhu, SJ and Zhou, YD and Hu, G and Hong, Q}, title = {Terrimonas soli sp. nov., isolated from farmland soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {819-823}, doi = {10.1099/ijsem.0.002590}, pmid = {29458527}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; *Farms ; Fatty Acids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-staining-negative, aerobic, non-motile and rod-shaped bacterium that produced yellow viscous colonies, designated FL-8T, was isolated from farmland soil in Chuzhou, Anhui province, PR China. 16S rRNA gene sequence similarities between strain FL-8T and the type strains of species of the genus Terrimonas with validly published names ranged from 94.6 to 96.1 %. Strain FL-8T contained iso-C15 : 1 G, iso-C15 : 0 and iso-C17 : 0 3-OH as the predominant fatty acids. The predominant polar lipid of strain FL-8T was phosphatidylethanolamine. The sole respiratory quinone of strain FL-8T was MK-7 and the DNA G+C content was 44.8 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic data, strain FL-8T is considered to represent a novel species of the genus Terrimonas, for which the name Terrimonassoli sp. nov. is proposed. The type strain is FL-8T (=CCTCC AB 2017059T=JCM 32095T).}, } @article {pmid29458522, year = {2018}, author = {Yang, D and Cha, S and Choi, J and Seo, T}, title = {Paenibacillus mobilis sp. nov., a Gram-stain-negative bacterium isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1140-1145}, doi = {10.1099/ijsem.0.002643}, pmid = {29458522}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-negative bacterium, designated strain S8T, was isolated from a soil sample obtained in Gyeonggi Province, Republic of Korea. Cells of strain S8T were endospore-forming, motile by means of peritrichous flagella, and rod-shaped. S8T colonies were round, convex, wavy and white. Strain S8T grew optimally at 37 °C, pH 6-8, and up to 2.0 % (w/v) NaCl. Based on 16S rRNA gene sequence similarity, strain S8T was affiliated with the genus Paenibacillus in the family Paenibacillaceae and was most closely related to Paenibacillus yonginensis DCY84T and Paenibacillus physcomitrellae XBT (98.8 and 97.1 % sequence similarity). The DNA G+C content of the novel strain was 53.1±0.3 mol%. Strain S8T contained diphosphatidylglycerol, phosphatidylglycerol, two phospholipids, four aminophospholipids, an aminolipid and three unidentified lipids. The major fatty acid was anteiso-branched C15 : 0. The quinone was menaquinone MK-7. The peptidoglycan of strain S8T contained meso-diaminopimelic acid. The DNA-DNA hybridization values of strain S8T with P. yonginensis KCTC 33428T and P. physcomitrellae DSM 29851T were 44 % and 32 %, respectively. Data from the DNA-DNA hybridization, biochemical, phylogenetic and physiological analyses indicate that strain S8T (=KCTC 33848T=JCM 31672T) represents a novel species of the genus Paenibacillus, for which the name Paenibacillus mobilis sp. nov. is proposed.}, } @article {pmid29458509, year = {2018}, author = {Feng, GD and Yang, SZ and Zhu, HH and Li, HP}, title = {Emended descriptions of the species Sphingomonas adhaesiva Yabuuchi et al. 1990 and Sphingomonas ginsenosidimutans Choi et al. 2011.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {970-973}, doi = {10.1099/ijsem.0.002557}, pmid = {29458509}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sphingomonas/*classification ; }, abstract = {During the phylogenetic study of the genus Sphingomonas and its closely related genera, we found that there existed errors in the 16S rRNA gene sequence of the type strain of the type species of Sphingomonas adhaesiva (D13722). Data suggested the wrong sequence should be replaced by the sequence under the accession number KY927401. As the new sequence shared 99.6 % 16S rRNA gene sequence similarity with that of Sphingomonas ginsenosidimutans, the relationship between these two species was reevaluated in the present study. Analyses, based on the whole genome sequences, phenotypic characteristics and fatty acid profiles clearly show that S. adhaesiva and Sphingomonas ginsenosidimutans are two distinct species of the genus Sphingomonas. Considering the errors in the original descriptions of S. adhaesiva and S. ginsenosidimutans, we have emended the descriptions of the two species.}, } @article {pmid29458507, year = {2018}, author = {Sakamoto, M and Iino, T and Hamada, M and Ohkuma, M}, title = {Parolsenella catena gen. nov., sp. nov., isolated from human faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1165-1172}, doi = {10.1099/ijsem.0.002645}, pmid = {29458507}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Adult ; Bacteria, Anaerobic/classification/genetics/isolation & purification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Feces/*microbiology ; Genes, Bacterial ; Humans ; Japan ; Male ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Strain 2CBEGH3T, which is an obligately anaerobic, non-pigmented, non-spore-forming, non-motile, Gram-stain-positive coccobacillus, was isolated from a faecal sample of a healthy Japanese man. The 16S rRNA gene sequence analysis showed that strain 2CBEGH3T represented a member of the family Atopobiaceae and formed a monophyletic cluster with Olsenella uli DSM 7084T (93.6 % sequence similarity), Olsenella umbonata strain lac31T (93.0 %), Olsenella profusa JCM 14553T (92.7 %) and Olsenella scatoligenes strain SK9K4T (92.7 %) as closest neighbours and Atopobium species. The hsp60 gene sequence analysis supported the phylogenetic relationships based on the 16S rRNA gene sequences, with sequence similarity values of 82.1-84.7 % to the four species described above. A unique three-base (one amino acid residue) insertion was found in the alignment regions of the hsp60 gene sequence of strain 2CBEGH3T. The major end products from d-glucose were d- and l-lactic acids produced at the ratio of 75 : 25, while four species of the genus Olsenella produced d- and l-lactic acids at ratios of 94-98 : 2-6. The isolate formed characteristic crater-like colonies on Eggerth-Gagnon agar plates. The major cellular fatty acids were C18 : 1ω9c, C18 : 1ω9c dimethyl acetal (DMA) and C16 : 0 DMA. The G+C content of the genomic DNA was 68.4 mol%. On the basis of these data, strain 2CBEGH3T represents a novel species in a novel genus of the family Atopobiaceae, for which the name Parolsenella catena gen. nov., sp. nov. is proposed. The type strain of P. catena is 2CBEGH3T (=JCM 31932T=DSM 105194T).}, } @article {pmid29458506, year = {2018}, author = {Trujillo, ME and Oren, A}, title = {Avoiding 'salami slicing' in publications describing new prokaryotic taxa.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {977-978}, doi = {10.1099/ijsem.0.002634}, pmid = {29458506}, issn = {1466-5034}, } @article {pmid29458505, year = {2018}, author = {Yan, ZF and Lin, P and Li, CT and Kook, M and Yi, TH}, title = {Actinotalea solisilvae sp. nov., isolated from forest soil and emended description of the genus Actinotalea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {788-794}, doi = {10.1099/ijsem.0.002584}, pmid = {29458505}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/chemistry ; }, abstract = {A Gram-stain-positive, aerobic, non-motile and short-rod-shaped actinobacterium, designated THG-T121T, was isolated from forest soil. Growth occurred at 10-40 °C (optimum 28-30 °C), at pH 6-8 (optimum 7) and at 0-4 % NaCl (optimum 1 %). Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbours of strain THG-T121T were identified as Actinotalea ferrariae KCTC 29134T (97.9 %), Actinotalea fermentans KCTC 3251T (97.3 %), Cellulomonas carbonis KCTC 19824T (97.2 %). 16S rRNA gene sequence similarities among strain THG-T121T and other recognized species were lower than 97.0 %. The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two phosphatidylinositol mannosides, one unidentified phospholipid, three unidentified glycolipids and one unidentified lipid. The isoprenoid quinone was menaquinone (MK-10(H4)). The major fatty acids were anteiso-C15 : 0, anteiso-C15 : 1 A, C16 : 0, iso-C16 : 0, anteiso-C17 : 0 and iso-C17 : 0. The whole-cell sugars of strain THG-T121T were rhamnose, ribose, mannose and glucose. The peptidoglycan type of strain THG-T121T is A4β, containing l-Orn-D-Ser-L-Asp. The DNA G+C content of strain THG-T121T was 72.4 mol%. DNA-DNA hybridization values between strain THG-T121T and A. ferrariae KCTC 29134T, A. fermentans KCTC 3251T and C. carbonis KCTC 19824T were 30.2 % (27.3 %, reciprocal analysis), 28.4 %, (17.3 %) and 16.9 %, (9.3 %), respectively. On the basis of the phylogenetic analysis, chemotaxonomic data, physiological characteristics and DNA-DNA hybridization data, strain THG-T121T represents a novel species of the genus Actinotalea, for which the name Actinotaleasolisilvae sp. nov. is proposed. The type strain is THG-T121T (=KACC 19191T=CGMCC 4.7389T).}, } @article {pmid29458504, year = {2018}, author = {Tang, L and Zhang, Z and Xie, R and Jiao, N and Zhang, Y}, title = {Salinisphaera aquimarina sp. nov., isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1130-1134}, doi = {10.1099/ijsem.0.002638}, pmid = {29458504}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, rod-shaped, motile bacterium with a subpolar flagellum, designated strain CCMM005T, was isolated from offshore seawater at Qingdao, China. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain CCMM005T belonged to the genus Salinisphaera and exhibited highest 16S rRNA gene sequence similarity to Salinisphaera dokdonensis CL-ES53T (96.9 %). It showed lower sequence similarities (94.9-96.4 %) with all other representatives of the genus Salinisphaera. Optimal growth occurred in the presence of 4 % (w/v) NaCl, at 30 °C and at pH 7.0. The polar lipids of strain CCMM005T consisted of phosphatidylethanolamine, phosphatidylcholine, phosphatidylglycerol, one unidentified phosphoglycolipid and one unidentified phospholipid. The predominant isoprenoid quinone was Q-8. The major fatty acids were C19 : 0cyclo ω8c, C18 : 0 and C18 : 1ω7c. The DNA G+C content of strain CCMM005T was 65.3 mol%. On the basis of data from this polyphasic study, strain CCMM005T is considered to represent a novel species of the genus Salinisphaera, for which the name Salinisphaera aquimarina sp. nov. is proposed. The type strain is CCMM005T (=MCCC 1K03246T=KCTC 52640T).}, } @article {pmid29458503, year = {2018}, author = {Hozzein, WN and Yang, ZW and Alharbi, SA and Alsakkaf, WAA and Asem, MD and Xiao, M and Salam, N and Li, WJ}, title = {Georgenia deserti sp. nov., a halotolerant actinobacterium isolated from a desert sample.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1135-1139}, doi = {10.1099/ijsem.0.002640}, pmid = {29458503}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Desert Climate ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Saudi Arabia ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain SYSU D8004T was isolated from a sample collected from an arid area in Saudi Arabia. The isolate was Gram-stain-positive, non-motile, aerobic and non-spore-forming. It could grow at 4-45 °C, at pH 6.0-10.0 and in the presence of up to 17 % (w/v) NaCl. Pairwise comparison of the 16S rRNA gene sequences indicated that strain SYSU D8004T shared highest sequence similarity with Georgenia halophila YIM 93316T (96.5 %). Menaquinone MK-8(H4) was detected as the respiratory quinone. The polar lipid profile of strain SYSU D8004T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two phosphatidylinositol mannosides, two unidentified phospholipids and an unidentified glycolipid. Strain SYSU D8004T contained anteiso-C15 : 0, iso-C15 : 0 and C14 : 0 as the predominant fatty acids (>10 %). Galactose, glucose and rhamnose were detected as whole-cell sugars. Based on analyses of the phenotypic, genotypic and phylogenetic characteristics, it was determined that strain SYSU D8004T could be differentiated from other closely related members of the genus Georgenia. Strain SYSU D8004T is therefore considered to represent a novel species of the genus Georgenia, for which the name Georgenia deserti sp. nov. is proposed. The type strain is SYSU D8004T (=CGMCC 1.15793T=KCTC 39987T).}, } @article {pmid29458502, year = {2018}, author = {Hezbri, K and Nouioui, I and Rohde, M and Spröer, C and Schumann, P and Gtari, M and Klenk, HP and Montero-Calasanz, MDC and Ghodhbane-Gtari, F}, title = {Blastococcus xanthinilyticus sp. nov., isolated from monument.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1177-1183}, doi = {10.1099/ijsem.0.002646}, pmid = {29458502}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Architecture ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tunisia ; Vitamin K 2/chemistry ; }, abstract = {A novel, non-motile, coccoid, Gram-stain-positive actinobacterium, designated BMG 862T, was isolated from a marble sample collected from the Bulla Regia monument, Northern Tunisia. Its taxonomic position was determined using a polyphasic approach. Results from chemotaxonomic analyses showed MK-9(H4), MK-8(H4) and MK-9(H2) as the predominant menaquinones. The major polar lipids comprised diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylinositol, glycophosphatidylinositol, hydroxy-phosphatidylethanolamine and three unidentified phospholipids. The fatty acids consisted of significant amounts (≥10 %) of iso-C16 : 0, C17 : 1ω8c, iso-C15 : 0 and C16 : 1ω7c. Phylogenetic analysis on the basis of 16S rRNA gene sequence comparisons showed that strain BMG 862T belongs to the genus Blastococcus, being most closely related to Blastococcus saxobsidens (=DSM 44509T) (99.5 %) and Blastococcus capsensis (=DSM 46835T=CECT 8876T) (99.3 %). The genomic DNA G+C content of the organism was 74.7 mol%. Results of DNA-DNA hybridization and physiological tests allowed differentiation of strain BMG 862T from related species. The strain was also characterized by its ability to hydrolyse xanthine. On the basis of phenotypic and molecular characteristics, strain BMG 862T (=DSM 46842T=CECT 8884T) represents the type strain of a novel species of the genus Blastococcus, for which the name Blastococcus xanthinilyticus sp. nov. is proposed.}, } @article {pmid29458501, year = {2018}, author = {Fang, Y and Chen, A and Dai, H and Huang, Y and Kan, B and Wang, D}, title = {Vibrio fujianensis sp. nov., isolated from aquaculture water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1146-1152}, doi = {10.1099/ijsem.0.002642}, pmid = {29458501}, issn = {1466-5034}, mesh = {*Aquaculture ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Genes, Bacterial ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vibrio/*classification/genetics/isolation & purification ; *Water Microbiology ; }, abstract = {A Gram-stain-negative, facultatively anaerobic strain, designated FJ201301T, was isolated from aquaculture water collected from Fujian province, China. Phylogenetic analysis of 16S rRNA gene sequences indicated that strain FJ201301T belonged to the genus Vibrio, formed a distinct cluster with Vibriocincinnatiensis ATCC 35912T and shared the highest similarity with Vibriosalilacus CGMCC 1.12427T. A 15 bp insertion found in the 16S rRNA gene was a significant marker that distinguished strain FJ201301T from several phylogenetic neighbours (e.g. V. cincinnatiensis). Multilocus sequence analysis of eight genes (ftsZ, gapA, gyrB, mreB, pyrH, recA, rpoA and topA; concatenated 4135 bp sequence) showed that, forming a long and independent phylogenetic branch, strain FJ201301T clustered with V. cincinnatiensis ATCC 35912T, Vibrioinjenensis KCTC 32233T and Vibriometschnikovii CIP 69.14T clearly separated from V. salilacus CGMCC 1.12427T. Furthermore, the highest in silico DNA-DNA hybridization and average nucleotide identity values between strain FJ201301T and the closest related species were 26.3 and 83.1 % with V. cincinnatiensis ATCC 35912T, less than the proposed cutoff levels for species delineation, i.e. 70 and 95 %, respectively. Biochemical, sequence and genomic analysis suggested the designation of strain FJ201301T representing a novel species of the genus Vibrio, for which the name Vibrio fujianensis sp. nov. is proposed. The type strain is FJ201301T (=DSM 104687T=CGMCC 1.16099T).}, } @article {pmid29458500, year = {2018}, author = {Hahnke, S and Langer, T and Klocke, M}, title = {Proteiniborus indolifex sp. nov., isolated from a thermophilic industrial-scale biogas plant.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002591}, pmid = {29458500}, issn = {1466-5034}, abstract = {A novel strictly anaerobic bacterium, designated strain BA2-13T, was isolated from a thermophilic industrial-scale biogas plant. Cells were rod-shaped and Gram-stain-positive. Growth occurred at temperatures of 25 to 50 °C and between pH 6.3 and 9.5. Strain BA2-13T produced indole. Cell growth was stimulated by yeast extract, peptone, meat extract, a mixture of 20 amino acids, glucose, pyruvate and ribose. When grown on peptone and yeast extract, the main fermentation products were acetic acid, H2 and CO2. The predominant cellular fatty acids were iso-C15 : 0 and iso-C14 : 0 3-OH. Major polar lipids were diphosphatidylglycerol, glycolipids, phospholipids and phosphatidylgycerol. Phylogenetic analysis based on 16S rRNA gene nucleotide sequence analysis placed strain BA2-13T within the order Clostridiales showing closest affiliation with Proteiniborusethanoligenes with 95.9 % sequence identity. Physiological, genotypic and chemotaxonomic differences of strain BA2-13T from P. ethanoligenes support the description of a new species within the genus Proteiniborus for which we suggest the name Proteiniborusindolifex sp. nov. (type strain BA2-13T=DSM 103060T=LMG 29818T).}, } @article {pmid29458499, year = {2018}, author = {Whitman, WB and Oren, A and Chuvochina, M and da Costa, MS and Garrity, GM and Rainey, FA and Rossello-Mora, R and Schink, B and Sutcliffe, I and Trujillo, ME and Ventura, S}, title = {Proposal of the suffix -ota to denote phyla. Addendum to 'Proposal to include the rank of phylum in the International Code of Nomenclature of Prokaryotes'.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {967-969}, doi = {10.1099/ijsem.0.002593}, pmid = {29458499}, issn = {1466-5034}, mesh = {Bacteria/*classification ; Classification ; *Terminology as Topic ; }, abstract = {As an addendum to the earlier proposal to include the rank of phylum in the International Code of Nomenclature of Prokaryotes (Oren et al., Int J Syst Evol Microbiol 2015;65:4284-4287) we propose the suffix -ota to denote phyla, replacing the somewhat awkward -aeota. We therefore present a new draft modified version of Rule 8 of the International Code of Nomenclature of Prokaryotes and a corrected list of names of phyla to be considered for validation after approval of the proposal to include the rank of phylum in the Code.}, } @article {pmid29458498, year = {2018}, author = {Cao, YR and He, ZK and Guo, Y and Yang, XX and Liang, LM}, title = {Actinorectispora metalli sp. nov., a novel actinomycete isolated from a mine and emended description of the genus Actinorectispora.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1023-1027}, doi = {10.1099/ijsem.0.002620}, pmid = {29458498}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Mining ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinomycete, designated strain KC 198T, was isolated from rare earth mine. The results of analysis of the 16S rRNA gene sequence indicated that KC 198T was most closely related to Actinorectisporaindica YIM 75728T (98.4 %). Aerial hyphae differentiated into long, straight chains of cylindrical spores. Growth was observed at 10-45 °C (optimum 28 °C), with 0-10 % (w/v) NaCl (optimum, in the absence of NaCl) and at pH 6.0-8.0 (optimum pH 7.0). KC 198T possessed MK-9(H4) as the predominant respiratory quinone and a minor amount of MK-10(H4). Polar lipids detected were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and phosphatidylinositol mannoside. Three unidentified lipids were also detected. The main cellular fatty acids were iso-C16 : 0 (30.9 %), iso-C16 : 1H (22.9 %) and iso-C15 : 0 (14.8 %). The genomic DNA G+C content was 66.8 mol%. On the basis of the phenotypic and genotypic characteristics, we propose that strain KC 198T represents a novel species of the genus Actinorectispora. The name Actinorectispora metalli sp. nov. is, therefore, proposed for the novel species with the type strain KC 198T (=CCTCC AA 2015043T=KCTC 39718T). The description of the genus Actinorectispora has also been emended.}, } @article {pmid29458497, year = {2018}, author = {Qu, JH and Zhang, LJ and Fu, YH and Li, XD and Li, HF and Tian, HL}, title = {A novel genus of the class Actinobacteria, Longivirga aurantiaca gen. nov., sp. nov., isolated from lake sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {942-946}, doi = {10.1099/ijsem.0.002615}, pmid = {29458497}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Lakes/*microbiology ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinobacterial strain, designated X5T, was isolated from the sediment of Taihu Lake in China and was subjected to a polyphasic taxonomic characterization. The strain formed orange-red colonies comprising aerobic, Gram-stain-negative, rod-shaped cells on R2A agar. Phylogenetic analysis based on the 16S rRNA gene sequences revealed that the organism was closely related to the genus Sporichthya and consistently formed a distinct clade along with the members of this genus. The closest phylogenetic neighbour was Sporichthya polymorpha NBRC 12702T with 93.7 % 16S rRNA gene sequence similarity. The major fatty acids (>10 %) were iso-C16 : 0 (18.7 %), C18 : 1ω9c (18.6 %) and C17 : 1ω8c (14.0 %). The genomic DNA G+C content was 74.4 mol%. The organism contained menaquinone MK-8(H2), MK-9(H4) and an unidentified menaquinone. Polar lipids were composed of phosphatidylglycerol, an unidentified lipid, two unidentified phospholipids and two unidentified aminolipids. The whole-cell sugars contained ribose, xylose, mannose, glucose and galactose. The cell-wall peptidoglycan contained ll-diaminopimelic acid. Based on the physiological, biochemical and chemotaxonomic data, the organism is proposed to represent a novel genus and species, for which the name Longivirga aurantiaca gen. nov., sp. nov. is proposed. The type strain is X5T (=CGMCC 4.7317T=NBRC 112237T).}, } @article {pmid29458496, year = {2018}, author = {Kämpfer, P and Rekha, PD and Busse, HJ and Arun, AB and Priyanka, P and Glaeser, SP}, title = {Halomonas malpeensis sp. nov., isolated from rhizosphere sand of a coastal sand dune plant.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1037-1046}, doi = {10.1099/ijsem.0.002616}, pmid = {29458496}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Halomonas/*classification/genetics/isolation & purification ; India ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-endospore-forming organism, isolated from the rhizosphere sand of a coastal sand dune plant was studied for its taxonomic position. On the basis of 16S rRNA gene sequence similarity comparisons, strain YU-PRIM-29T was grouped within the genus Halomonas and was most closely related to Halomonas johnsoniae (97.5 %). The 16S rRNA gene sequence similarity to other Halomonas species was <97.5 %. Strain YU-PRIM-29T grew optimally at 28 °C (growth range, 10-36 °C), at a pH of 7-9 (growth range, pH 5.5-12.0) and in the presence of 0.5 to 5 % (w/v) NaCl (growth up to 20 % NaCl). The fatty acid profile from whole-cell hydrolysates supported the allocation of the strain to the genus Halomonas. The fatty acids C18 : 1ω7c and C16 : 0 were found as major compounds, followed by the hydroxylated fatty acid C12 : 0 3-OH. The quinone system consisted predominantly of ubiquinone Q-9. The polar lipid profile was composed of the major lipids diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. In the polyamine pattern, spermidine was the predominant compound. The DNA G+C content was 64.8 mol%. In addition, the results of physiological and biochemical tests also allowed phenotypic differentiation of strain YU-PRIM-29T from its closest-related species. Hence, YU-PRIM-29T represents a new species of the genus Halomonas, for which we propose the name Halomonas malpeensis sp. nov., with YU-PRIM-29T (=LMG 28855T=CCM 8737T) as the type strain.}, } @article {pmid29458495, year = {2018}, author = {Dahal, RH and Kim, J}, title = {Simplicispira soli sp. nov., a betaproteobacterium isolated from stream bank soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002618}, pmid = {29458495}, issn = {1466-5034}, abstract = {Two strains of soil bacteria, designated CA-16T and CA-161, were isolated from a sample of stream bank soil near Kyonggi University. Cells were strictly aerobic, Gram-stain-negative, catalase-negative, oxidase-positive, motile, non-spore-forming and rod-shaped. Colonies on tryptone soya agar were brownish cream in colour. Tyrosine, Tween 60 and Tween 40 were hydrolysed. The indole test was positive. Malic acid, lactic acid and valeric acid were assimilated. Phylogenetic analysis based on their 16S rRNA gene sequences revealed that strains CA-16T and CA-161 formed a lineage within the family Comamonadaceae of the class Betaproteobacteria that were distinct from various species of the genus Simplicispira. Strain CA-16T was most closely related to Simplicispira metamorpha DSM 1837T (97.86 % sequence similarity), Simplicispira limi EMB325T (97.72 %), Simplicispira psychrophila DSM 11588T (96.83 %) and Simplicispira piscis RSG39T (96.71 %). Both strains contained Q-8 as the major isoprenoid quinone. The major polar lipids of the strains were phosphatidylglycerol, phosphatidylethanolamine and diphosphatidylglycerol. The major cellular fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), C18 : 1ω7c-11methyl, C16 : 0, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C12 : 0. The DNA G+C contents of the strains were 63.9-64.4 mol%. DNA-DNA hybridization similarities between strain CA-16T and other closest members of the genus Simplicispira ranged from 16 % to 24 %. On the basis of phenotypic, genotypic, chemotaxonomic and phylogenetic analyses, strains CA-16T and CA-161 represent a single novel species of the genus Simplicispira, for which the name Simplicispirasoli sp. nov. is proposed. The type strain is CA-16T (=KEMB 9005-529T=KACC 19107T=NBRC 112689T).}, } @article {pmid29458494, year = {2018}, author = {Hwang, WM and Kim, SM and Kang, K and Ahn, TY}, title = {Uliginosibacterium sediminicola sp. nov., isolated from freshwater sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {924-929}, doi = {10.1099/ijsem.0.002611}, pmid = {29458494}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/*microbiology ; Geologic Sediments/*microbiology ; Hydroxybutyrates/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Polyesters/chemistry ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodocyclaceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {Strain M1-21T is a Gram-stain-negative, strictly aerobic and short-rod-shaped bacterium, motile by means of a single polar flagellum; it was isolated from freshwater sediment in Korea. It grew at 10-40 °C (optimum 25 °C), pH 6.0-8.0 (optimum pH 7.0) and with 0-0.75 % (w/v) NaCl (optimal growth occurred in the absence of NaCl) on R2A agar, and it accumulated poly-β-hydroxybutyrate granules inside the cells. According to 16S rRNA gene sequence analysis, strain M1-21T showed highest sequence similarity with Uliginosibacterium gangwonense (94.7 %) and Uliginosibacterium paludis (94.4 %). Phylogenetic analysis of the 16S rRNA gene sequences revealed that strain M1-21T belongs to the genus Uliginosibacterium. The DNA G+C content of strain M1-21T was 61.9 mol%. The predominant respiratory quinone was ubiquinone-8. The major fatty acids (>10 % of the total) were C16 : 0 and summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), and the major polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Strain M1-21T showed distinct phenotypic characteristics that differentiated it from species of the genus Uliginosibacterium. Based on these results, strain M1-21T represents a novel species of the genus Uliginosibacterium, for which the name Uliginosibacterium sediminicola sp. nov. is proposed. The type strain is M1-21T (=KACC 19271T=JCM 32000T).}, } @article {pmid29458493, year = {2018}, author = {Shin, NR and Kang, W and Tak, EJ and Hyun, DW and Kim, PS and Kim, HS and Lee, JY and Sung, H and Whon, TW and Bae, JW}, title = {Blautia hominis sp. nov., isolated from human faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1059-1064}, doi = {10.1099/ijsem.0.002623}, pmid = {29458493}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Clostridiales/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/analysis ; Feces/*microbiology ; Fermentation ; Humans ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; }, abstract = {A strictly anaerobic, Gram-stain-positive, non-motile and coccoid- or oval-shaped bacterium, designated strain KB1T, was isolated from a faecal sample of a patient with diverticulitis in South Korea. Degeneracies in the 16S rRNA gene sequence of strain KB1T were resolved by cloning, which yielded five different sequences with heterogeneity. Phylogenetic analysis based on the 16S rRNA gene sequences showed that strain KB1T formed a monophyletic branch with species in the genus Blautia, with highest sequence similarity to the type strain of Blautia producta (97.7-98.9 %), followed by Blautia coccoides (97.5-98.1 %). Strain KB1T was able to grow at temperatures of between 15 and 42 °C, with optimal growth at 37 °C, and in the presence of 20 % dehydrated bile. Acetic acid, succinic acid, lactic acid and fumaric acid were produced by strain KB1T from Gifu anaerobic medium broth as metabolic fermentation end-products. The major cellular fatty acids of strain KB1T were C14 : 0, C16 : 0 and C16 : 0 dimethyl aldehyde. The DNA G+C content was 46.3 mol%. The average nucleotide identity value between strain KB1T and the type strain of B. producta was 84.1 %. On the basis of polyphasic analysis, strain KB1T represents a novel species in the genus Blautia, for which the name Blautia hominis sp. nov. is proposed. The type strain is KB1T (=KCTC 15618T=JCM 32276T).}, } @article {pmid29458492, year = {2018}, author = {Liu, Y and Rao, Q and Tu, J and Zhang, J and Huang, M and Hu, B and Lin, Q and Luo, T}, title = {Acinetobacter piscicola sp. nov., isolated from diseased farmed Murray cod (Maccullochella peelii peelii).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {905-910}, doi = {10.1099/ijsem.0.002608}, pmid = {29458492}, issn = {1466-5034}, mesh = {Acinetobacter/*classification/genetics/isolation & purification ; Animals ; Aquaculture ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fish Diseases/*microbiology ; Fishes/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A taxonomic study was carried out on strain LW15T, which was isolated from the external lesions of diseased farmed Murray cod (Maccullochella peelii peelii) from an intensive culture pond. Cells of strain LW15T were Gram-negative, facultative-anaerobic, non-motile, and both coccobacillus- and bacillus-shaped. Growth was observed at NaCl concentrations of 0-2 % (w/v) (optimum, 0 %), 4-32 °C (optimum, 25-28 °C) and pH 5.0-9.0 (optimum, 7.0). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain LW15T was affiliated to the genus Acinetobacter, showing the highest similarity to Acinetobacter guillouiae CIP 63.46T (97.7 %) and other Acinetobacter species with validly published names (93.5-97.6 %). Whole-genome sequencing and phylogeny reconstruction based on a core set of 1061 Acinetobacter genes indicated that strain LW15T was most closely related to the clade formed by A. guillouiae CIP 63.46T and Acinetobacter bereziniae CIP 70.12T and distantly related to any of the described species of genus Acinetobacter. Furthermore, strain LW15T could be distinguished from all known Acinetobacter species by its ability to assimilate β-alanine and l-arginine, but not d-glucose. The principal fatty acids were C18 : 1ω9c, C16 : 0 and C16 : 1ω7c/C16 : 1ω6c. The major respiratory quinone was Q-9. Polar lipids of strain LW15T comprised diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, four phospholipids, aminolipid and two unknown lipids. Based on its phenotypic and genotypic data, strain LW15T represents a novel species of the genus Acinetobacter, for which the name Acinetobacterpiscicola sp. nov. is proposed. The type strain is LW15T (=MCCC 1K03337T=CICC 24241T=KCTC 62134T=JCM 32101T).}, } @article {pmid29458491, year = {2018}, author = {Kuncharoen, N and Pittayakhajonwut, P and Tanasupawat, S}, title = {Micromonospora globbae sp. nov., an endophytic actinomycete isolated from roots of Globba winitii C. H. Wright.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1073-1077}, doi = {10.1099/ijsem.0.002625}, pmid = {29458491}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Micromonospora/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; *Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Thailand ; Vitamin K 2/chemistry ; Zingiberaceae/*microbiology ; }, abstract = {A novel endophytic actinomycete, strain WPS1-2T, isolated from a root of Globba winitii C. H. Wright, was characterized taxonomically by using a polyphasic approach. Strain WPS1-2T exhibited identical characteristics to the members of the genus Micromonospora. Single spores were observed directly on substrate mycelia. The cell-wall peptidoglycan of the strain contained meso-diaminopimelic acid and 3-OH-meso-diaminopimelic acid. Whole-cell hydrolysates contained glucose, ribose, arabinose and xylose. The predominant menaquinones were MK-10(H8) and MK-10(H10). The major cellular fatty acids consisted of iso-C15 : 0, iso-C16 : 0 and anteiso-C15 : 0. According to the 16S rRNA gene sequence of the strain, WPS1-2T showed highest similarity to Micromonospora costi CS1-12T (99.02 %). Phylogenetic analysis of the gyrase subunit B (gyrB) gene indicated that the strain was related to M. costi CS1-12T. The DNA G+C content was 73.7 mol%. The strain could be distinguished from closely related type strains by using a combination of morphological, chemotaxonomic, physiological and biochemical data together with DNA-DNA relatedness values. Based on these observations, strain WPS1-2T is considered to represent a novel species of the genus Micromonospora, for which the name Micromonospora globbae sp. nov. is proposed. The type strain is WPS1-2T (=KCTC 39787T=NBRC 112325T=TISTR 2405T).}, } @article {pmid29458490, year = {2018}, author = {Shi, MJ and Wang, C and Wang, XT and Du, ZJ}, title = {Halioglobus lutimaris sp. nov., isolated from coastal sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {876-880}, doi = {10.1099/ijsem.0.002601}, pmid = {29458490}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Phosphatidylglycerols/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative, strictly aerobic, non-flagellated and rod-shaped bacterium, designated HF004T, was isolated from a marine sediment sample collected from the coast of Weihai, China. The strain grew optimally at 28 °C, pH 7.5-8.0 and in the presence of 2.0-3.0 % (w/v) NaCl. Based on the 16S rRNA gene sequence analysis, strain HF004T was a member of the genus Halioglobus, appearing to be closely related to Halioglobus pacificus (96.1 %) and Halioglobus japonicus (95.6 %). The major fatty acids were summed feature 3 (i.e. C16 : 1ω7c and/or iso-C15 : 0 2-OH), C17 : 1ω8c and C18 : 1ω7c. The major polar lipids were diphosphatidylglycerol, phosphatidylethanolamine and phosphatidylglycerol. The predominant respiratory quinone was Q-8. The DNA G+C content was 57.2 mol%. Cells of strain HF004T were rod-shaped and formed circular, mucous and beige-pigmented colonies on marine agar after incubation for 72 h at 28 °C. On the basis of phenotypic, genotypic and phylogenetic evidence, strain HF004T is presented as a novel species, for which the name Halioglobus lutimaris sp. nov. is proposed. The type strain is HF004T (=KCTC 42395T=MCCC 1H00127T).}, } @article {pmid29458489, year = {2018}, author = {Rahi, P and Kurli, R and Pansare, AN and Khairnar, M and Jagtap, S and Patel, NB and Dastager, SG and Lawson, PA and Shouche, YS}, title = {Microbacterium telephonicum sp. nov., isolated from the screen of a cellular phone.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1052-1058}, doi = {10.1099/ijsem.0.002622}, pmid = {29458489}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; *Cell Phone ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; India ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/chemistry ; }, abstract = {A cultivation-based study of the microbial diversity of cellular phone screens led to the isolation of a Gram-stain-positive, aerobic, rod-shaped and non-endospore-forming bacterium, designated S2T63T, exhibiting phenotypic and genotypic characteristics unique to the type strains of closely related species. Phylogenetic analysis based on 16S rRNA gene sequences indicated that the strain is a member of Microbacterium, and most closely related to Microbacterium aurantiacum IFO 15234T and Microbacterium kitamiense Kitami C2T. The DNA-DNA relatedness values of the strain S2T63T to M. aurantiacum KACC 20510T, M. kitamiense KACC 20514Tand Microbacterium laevaniformans KACC 14463T were 65 % (±4), 29.5 % (±3) and 55.9 % (±4), respectively. The genomic DNA G+C content was 71.8 mol%. The major fatty acids were anteiso-C15 : 0, iso-C16 : 0, C16 : 0 and anteiso-C17 : 0. The main polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol and two unidentified polar lipids. The peptidoglycan contained the amino acids glycine, lysine, alanine and glutamic acid, with substantial amounts of hydroxy glutamic acid detected, which is characteristic of peptidoglycan type B1α. The predominant menaquinones were MK-12 and MK-13. Rhamnose, fucose and galactose were the whole-cell sugars detected. The strain also showed biofilm production, estimated by using crystal violet assay. Based on the results of the phenotypic and genotypic characterizations, it was concluded that the new strain represents a novel species of the genus Microbacterium, for which the name Microbacteriumtelephonicum is proposed, with S2T63T (=MCC 2967T=KACC 18715T=LMG 29293T) as the type strain.}, } @article {pmid29458488, year = {2018}, author = {Choi, JY and Kim, JH and Lee, PC}, title = {Flavobacterium kingsejongi sp. nov., a carotenoid-producing species isolated from Antarctic penguin faeces.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {911-916}, doi = {10.1099/ijsem.0.002610}, pmid = {29458488}, issn = {1466-5034}, mesh = {Animals ; Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Feces/microbiology ; Flavobacterium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spheniscidae/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; Zeaxanthins/*chemistry ; }, abstract = {Taxonomic studies were carried out on a carotenoid-producing strain, designated WV39T, isolated from the faeces of Antarctic penguins. Cells of strain WV39T were Gram-stain-negative, strictly aerobic, yellow and rod-shaped. 16S rRNA gene sequence analysis revealed that strain WV39T was closely related to Flavobacterium qiangtangense JCM 19739T (96.3 % similarity), Flavobacterium noncentrifugens NBRC 108844T (95.5 %) and Flavobacterium aquatile LMG 4008T (94.9 %). The predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 0 3-OH and summed feature 3 (comprising iso-C15 : 0 2-OH and/or C16 : 1ω7c). Menaquinone-6 was the sole quinone identified, and the major pigment was zeaxanthin. The major polar lipid was phosphatidylethanolamine. DNA-DNA relatedness of strain WV39T with respect to its closest phylogenetic neighbours was 41.8 % for F. qiangtangense JCM 19739T, 25.5 % for F. aquatile LMG 4008T and 25.2 % for F. noncentrifugens NBRC 108844T. The DNA G+C content of strain WV39T was 39.8 mol%. Based on the phenotypic, chemotaxonomic and phylogenetic data, strain WV39T is concluded to represent a novel species of the genus Flavobacterium, for which the name Flavobacteriumkingsejongi sp. nov. is proposed. The type strain is WV39T (=KCTC 42908T=CECT 9085T).}, } @article {pmid29458487, year = {2018}, author = {Zhang, S and Sun, C and Xie, J and Wei, H and Hu, Z and Wang, H}, title = {Defluviimonas pyrenivorans sp. nov., a novel bacterium capable of degrading polycyclic aromatic hydrocarbons.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {957-961}, doi = {10.1099/ijsem.0.002629}, pmid = {29458487}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Polycyclic Aromatic Hydrocarbons/*metabolism ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Rivers/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {An aerobic, Gram-stain-negative, rod-shaped, non-motile bacterium capable of degrading the polycyclic aromatic hydrocarbon pyrene was isolated from sediment of Pearl River and designated PrR001. 16S rRNA gene sequence analysis revealed that this strain was affiliated within the genus Defluviimonas in the family Rhodobacteraceae of the class Alphaproteobacteria and showed great similarity with the type strain Defluviimonas indica 20V17T (96.3 % similarity). The DNA G+C content of strain PrR001T was 68.3 mol%. The major cellular fatty acids comprised summed feature 8 (C18 : 1ω7c/C18 : 1ω6c), C19 : 0 cyclo ω8c, C18 : 0 3OH, and C18 : 0. The sole respiratory lipoquinone was ubiquinone-10. The main polar lipids were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, an unidentified aminolipid, an unidentified aminophospholipid and three unidentified phospholipids. Based on physiological, chemotaxonomic and phylogenetic analysis, strain PrR001T is suggested as a novel species in the genus Defluviimonas, for which the name Defluviimonas pyrenivorans sp. nov. is proposed. The type strain of Defluviimonas pyrenivorans is PrR001T (=CICC 24263T=KCTC 62192T).}, } @article {pmid29458486, year = {2018}, author = {Zhang, X and Liu, X and Lai, Q and Du, Y and Sun, F and Shao, Z}, title = {Muricauda indica sp. nov., isolated from deep sea water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002602}, pmid = {29458486}, issn = {1466-5034}, abstract = {A taxonomic study was carried out on strain 3PC125-7T, which was isolated from the deep sea water of the Indian Ocean. The bacterium was rod-shaped, non-flagellated, Gram-stain-negative, oxidase- and catalase-positive and strictly aerobic. Optimal growth was observed at 25-37 °C, at pH 7 and in 1-3 % (w/v) NaCl. On the basis of the results of 16S rRNA gene sequence analysis, strain 3PC125-7T represents a member of the genus Muricauda, with the highest sequence similarity to Muricauda olearia CL-SS4T (96.7 %), followed by Muricauda marina H19-56T (96.7 %) and nine other species of the genus Muricauda(93.5-95.8 %). The principal fatty acids of 3PC125-7T were iso-C15 : 0, iso-C17 : 0 3-OH and iso-C15 : 1G and the sole respiratory quinone was menaquinone-6. The polar lipids comprise phosphatidylethanolamine, six unidentified phospholipids and three unknown lipids. The genomic DNA G+C content of 3PC125-7T was 41.8 mol%. Based on the phylogenetic, phenotypic and chemotaxonomic data obtained in this study, strain 3PC125-7T is considered to represent a novel species in the genus Muricauda, for which the name Muricaudaindica sp. nov. is proposed, with the type strain 3PC125-7T (=MCCC 1A03198T=KCTC 52318T).}, } @article {pmid29458485, year = {2018}, author = {Nedashkovskaya, OI and Kim, SG and Stenkova, AM and Kukhlevskiy, AD and Zhukova, NV and Mikhailov, VV}, title = {Aquimarina algiphila sp. nov., a chitin degrading bacterium isolated from the red alga Tichocarpus crinitus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {892-898}, doi = {10.1099/ijsem.0.002606}, pmid = {29458485}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Pacific Ocean ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Rhodophyta/*microbiology ; Russia ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A strictly aerobic, Gram-stain-negative, rod-shaped, motile by gliding and yellow-orange pigmented flavobacterium, designated strain 9Alg 151T, was isolated from the Pacific red alga Tichocarpus crinitus. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain fell into the genus Aquimarina of the family Flavobacteriaceae with a 16S rRNA gene sequence similarity range of 94.2-98.2 % to the recognized species of the genus. Strain 9Alg 151T grew in the presence of 0.5-5 % NaCl and at 5-34 °C, and hydrolysed aesculin, agar, gelatin, starch, Tween 40, DNA and chitin. The predominant fatty acids were iso-C17 : 0 3-OH, iso-C15 : 0, iso-C15 : 1 G, iso-C15 : 0 3-OH, iso-C16 : 0, iso-C17 : 1ω8c and summed feature 3. The polar lipid profile comprised phosphatidylethanolamine, three unidentified aminolipids and three unidentified lipids. The major respiratory quinone was MK-6. The genomic DNA G+C content was 32.6 mol%. On the basis of 16S rRNA gene sequence data, and chemotaxonomic and phenotypic characteristics, strain 9Alg 151T represents a novel species of the genus Aquimarina, for which the name Aquimarina algiphila sp. nov. is proposed. The type strain is 9Alg 151T (=KCTC 23622T=KMM 6462T).}, } @article {pmid29458484, year = {2018}, author = {Kim, DU and Lee, H and Lee, S and Kim, SG and Park, AY and Ahn, JH and Ka, JO}, title = {Flavisolibacter metallilatus sp. nov., isolated from an automotive air conditioning system and emended description of the genus Flavisolibacter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {917-923}, doi = {10.1099/ijsem.0.002609}, pmid = {29458484}, issn = {1466-5034}, mesh = {*Air Conditioning ; *Automobiles ; Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile, rod-shaped and pale yellow-pigmented bacterium, designated strain TX0661T, was isolated from an automotive air conditioning system collected in the Republic of Korea. 16S rRNA gene sequence analysis showed that the strain TX0661T was grouped with members of the genus Flavisolibacter and the strain had 98.2-95.3 % 16S rRNA gene sequence similarities to the species of the genus Flavisolibacter. DNA-DNA relatedness between TX0661T and Flavisolibacter ginsenosidimutans KCTC 22818T and Flavisolibacter ginsengisoli KCTC 12657T was less than 30 %. The low levels of DNA-DNA relatedness identified strain TX0661T as a novel species in the genus Flavisolibacter. The strain grew at 28-37 °C (optimum, 37 °C), at pH 6.0-7.0 (optimum, pH 6.5) and in the presence of 0-0.5 % (w/v, optimum, 0.5 %) NaCl. It contained summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 and iso-C17 : 0 3-OH as major fatty acids and MK-7 as the predominant menaquinone. The polar lipid profile revealed that the presence of phosphatidylethanolamine, aminoglycophospholipid, two unidentified aminolipids and two unidentified lipids. The DNA G+C content of the strain was 49.1 mol%. Based on phenotypic, genotypic and chemotaxonomic data, strain TX0661T represents a novel species in the genus Flavisolibacter, for which the name Flavisolibactermetallilatus sp. nov. (=KACC 19145T=KCTC 52779T=NBRC 111784T) is proposed.}, } @article {pmid29458483, year = {2018}, author = {Kämpfer, P and Busse, HJ and Glaeser, SP}, title = {Marinicrinis lubricantis sp. nov., isolated from a coolant lubricant.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1018-1022}, doi = {10.1099/ijsem.0.002603}, pmid = {29458483}, issn = {1466-5034}, mesh = {Bacillales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Germany ; Glycolipids/chemistry ; *Lubricants ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, aerobic, endospore-forming bacterium isolated from a coolant lubricant was studied for its taxonomic allocation. On the basis of 16S rRNA gene sequences, strain KSS164-79T shared highest similarity (92.3-92.4 %) to type strains of the species Marinicrinis sediminis,Paenibacillus dongdonensis, Paenibacillus abyssi and Paenibacillus motobuensis. In phylogenetic trees based on the 16S rRNA gene, strain KSS164-79T always formed a distinct cluster with the type strain of M. sediminis. The fatty acid profile supported the grouping of the strain to the genus Marinicrinis. As major fatty acids, anteiso-C15 : 0, iso-C15 : 0 and iso-C16 : 0 were detected. The polar lipid profile contained the major components diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and two unidentified glycolipids. The major quinone was menaquinone MK-7. In addition, physiological and biochemical test results allowed the clear phenotypic differentiation of strain KSS164-79T from M. sediminis. Hence, KSS164-79T represents a novel species of the genus Marinicrinis, for which the name Marinicrinis lubricantis sp. nov. is proposed, with KSS164-79T (=DSM 104943T=LMG 30062T=CCM 8749T=CIP 111345T) as the type strain.}, } @article {pmid29458482, year = {2018}, author = {Niu, X and Cui, W and Cui, M and Zhang, X and Zhang, S and Xu, B and Gao, M}, title = {Sphingobacterium solani sp. nov., isolated from potato stems.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {1012-1017}, doi = {10.1099/ijsem.0.002605}, pmid = {29458482}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Stems/microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Solanum tuberosum/*microbiology ; Sphingobacterium/*classification/genetics/isolation & purification ; Vitamin K 2/chemistry ; }, abstract = {A Gram-stain-negative, non-motile, non-spore-forming bacterium, designated MLS-26-JM13-11T, was isolated from potato stems, collected in Guyuan County, Hebei Province, China. Strain MLS-26-JM13-11T could grow at 10-39 °C (optimum, 30 °C), pH 6.0-9.0 (optimum, pH 7.2) and in the presence of 0-4.0 % (w/v) NaCl (optimum, 1.0 % w/v). Phylogenetic analysis, based on 16S rRNA gene sequences, revealed that strain MLS-26-JM13-11T formed a stable clade with Sphingobacterium bambusae IBFC2009T and Sphingobacterium griseoflavum SCU-B140T, with the 16S rRNA gene sequence similarities ranging from 95.9 % to 97.0 %. The major cellular fatty acids comprised iso-C15 : 0 (36.9 %), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c, 34.0 %), C16 : 0 (3.0 %) and iso-C17 : 0 3-OH (13.4 %). Strain MLS-26-JM13-11T contained sphingoglycolipid, phosphatidyl ethanolamine, six unknown lipids, one unknown aminolipid, four unknown polarlipids and two unknown aminophospholipids. The isoprenoid quinone was MK-7. The DNA G+C content was 42.6 mol%. Furthermore, the average nucleotide identity and in silico estimated DNA-DNA reassociation values among MLS-26-JM13-11T and S. bambusae KCTC 22814T were in all cases below the respective threshold for species differentiation. On the basis of phenotypic, genotypic and phylogenetic evidence, strain MLS-26-JM13-11T (=ACCC 60057T=JCM 32274T) represents a novel species within the genus Sphingobacterium, for which the name Sphingobacterium solani sp. nov. is proposed.}, } @article {pmid29458481, year = {2018}, author = {Choi, S and Kang, JW and Yoon, JH and Seong, CN}, title = {Dokdonia flava sp. nov., isolated from the seaweed Zostera marina.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {899-904}, doi = {10.1099/ijsem.0.002607}, pmid = {29458481}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seaweed/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; Zosteraceae/*microbiology ; }, abstract = {A non-motile, proteorhodopsin-containing, yellow and rod-shaped bacterial strain, designated ZODW10T, was isolated from the seaweed Zostera marina collected from the West Sea, Republic of Korea. Cells were Gram-stain-negative, aerobic and non-motile. The isolate required sea salts for growth. A carotenoid pigment was produced. A phylogenetic tree based on 16S rRNA gene sequences showed that strain ZODW10T forms an evolutionary lineage within the radiation enclosing members of the genus Dokdonia with Dokdoniadiaphoros CIP 108745T (96.7 % sequence similarity) as its nearest neighbour. The major fatty acids were iso-C15:0, iso-C17 : 0 3-OH and iso-C15 : 1 G. Strain ZODW10T contained menaquinone 6 (MK-6) and phosphatidylethanolamine, an unidentified aminolipid and an unidentified polar lipid as the only isoprenoid quinone and the major polar lipids, respectively. The DNA G+C content of strain ZODW10T was 36 mol%. On the basis of the present polyphasic characterization, it is suggested that the isolate represents a novel species of the genus Dokdonia, for which the name Dokdonia flava sp. nov. (type strain, ZODW10T=KCTC 52953T=JCM 32293T) is proposed.}, } @article {pmid29458480, year = {2018}, author = {Pal, M and Kumari, M and Kiran, S and Salwan, R and Mayilraj, S and Chhibber, S and Gulati, A}, title = {Chryseobacterium glaciei sp. nov., isolated from the surface of a glacier in the Indian trans-Himalayas.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {865-870}, doi = {10.1099/ijsem.0.002600}, pmid = {29458480}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chryseobacterium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Ice Cover/*microbiology ; India ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel bacterial strain, IHBB 10212T, of the genus Chryseobacterium was isolated from a glacier near the Kunzum Pass located in the Lahaul-Spiti in the North-Western Himalayas of India. The cells were Gram-negative, aerobic, non-sporulating, single rods, lacked flagella, and formed yellow to orange pigmented colonies. The strain utilized maltose, trehalose, sucrose, gentibiose, glucose, mannose, fructose, mannitol, arabitol and salicin for growth. Flexirubin-type pigments were produced by strain IHBB 10212T. The 16S rRNA gene sequence analysis showed relatedness of strain IHBB 10212T to Chryseobacterium polytrichastri DSM 26899T (97.43 %), Chryseobacterium greenlandense CIP 110007T (97.29 %) and Chryseobacterium aquaticum KCTC 12483T (96.80 %). Iso-C15 : 0 and summed feature 3 (C16 : 1ω7c/C16 : 1ω6c) constituted the major cellular fatty acids. The polar lipids present were six unidentified aminolipids, one unidentified phospholipid and three unidentified lipids. MK-6 was identified as the major quinone. The DNA G+C content was 34.08 mol%. Digital DNA-DNA hybridization of strain IHBB 10212T with C. polytrichastri, C. greenlandense and C. aquaticum showed values far below the prescribed thresholds of 95 % for average nucleotide identity and 70 % for the Genome-to-Genome Distance Calculator for species delineation. Based on its differences from validly published Chryseobacterium species, strain IHBB 10212T is identified as a new species, for which the proposed name is Chryseobacterium glaciei sp. nov., with IHBB 10212T as the type strain (=MTCC 12457T=JCM 31156T=KACC 19170T).}, } @article {pmid29458479, year = {2018}, author = {Núñez-Montero, K and Leclercq, A and Moura, A and Vales, G and Peraza, J and Pizarro-Cerdá, J and Lecuit, M}, title = {Listeria costaricensis sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {844-850}, doi = {10.1099/ijsem.0.002596}, pmid = {29458479}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Costa Rica ; DNA, Bacterial/genetics ; *Food Industry ; Listeria/*classification/genetics/isolation & purification ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Waste Water/*microbiology ; }, abstract = {A bacterial strain isolated from a food processing drainage system in Costa Rica fulfilled the criteria as belonging to the genus Listeria, but could not be assigned to any of the known species. Phylogenetic analysis based on the 16S rRNA gene revealed highest sequence similarity with the type strain of Listeria floridensis (98.7 %). Phylogenetic analysis based on Listeria core genomes placed the novel taxon within the Listeria fleishmannii, L. floridensis and Listeria aquatica clade (Listeria sensu lato). Whole-genome sequence analyses based on the average nucleotide blast identity (ANI<80 %) indicated that this isolate belonged to a novel species. Results of pairwise amino acid identity (AAI>70 %) and percentage of conserved proteins (POCP>68 %) with currently known Listeria species, as well as of biochemical characterization, confirmed that the strain constituted a novel species within the genus Listeria. The name Listeria costaricensis sp. nov. is proposed for the novel species, and is represented by the type strain CLIP 2016/00682T (=CIP 111400T=DSM 105474T).}, } @article {pmid29458478, year = {2018}, author = {Teng, JLL and Tang, Y and Wong, SSY and Chiu, TH and Zhao, Z and Chan, E and Ngan, AHY and Lau, SKP and Woo, PCY}, title = {Tsukamurella ocularis sp. nov. and Tsukamurella hominis sp. nov., isolated from patients with conjunctivitis in Hong Kong.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {810-818}, doi = {10.1099/ijsem.0.002589}, pmid = {29458478}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Conjunctiva/*microbiology ; Conjunctivitis/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Hong Kong ; Humans ; Mycolic Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Three bacterial strains, HKU63T, HKU64 and HKU65T, were isolated from the conjunctival swabs of three patients with conjunctivitis in Hong Kong. The three strains were aerobic, Gram-stain-positive, catalase-positive, non-sporulating and non-motile bacilli and exhibited unique biochemical profiles distinguishable from closely related Tsukamurella species. 16S rRNA gene sequence analysis revealed that the three strains shared identical sequences with each other, being most closely related to Tsukamurella tyrosinosolvens and Tsukamurella pulmonis, sharing 99.9 % sequence identity. Sequence analysis of three additional housekeeping genes, groEL, secA and rpoB, revealed 100 % nucleotide sequence identity between HKU63T and HKU64, 94.2-97.0 % nucleotide sequence identities between HKU63T/HKU64 and HKU65T and the three strains shared 82.9-98.9 % sequence identities with other currently recognized Tsukamurella species. DNA-DNA hybridization confirmed that they were distinct from other known species of the genus Tsukamurella(23.0±4.2 to 50.7±3.7 % DNA-DNA relatedness), of which HKU63T and HKU64 represented the same species (≥95.2±4.8 % DNA-DNA relatedness) while HKU65T represented another species. Fatty acid, mycolic acid, cell-wall sugar and peptidoglycan analyses showed that they were typical of members of Tsukamurella. The G+C content of strains HKU63T, HKU64 and HKU65T were 71.3±1.9, 71.3±2.0 and 71.2±2.3 mol% (mean±sd; n=3), respectively. A novel species, Tsukamurella ocularis sp. nov. is proposed to accommodate strains HKU63T and HKU64, with HKU63T (=JCM 31969T=DSM 105034T) designated as the type strain whilst another novel species, Tsukamurella hominis sp. nov., is proposed to accommodate the third strain, HKU65T, which is designated as the type strain (=JCM 31971T=DSM 105036T).}, } @article {pmid29458477, year = {2018}, author = {Kwon, YM and Kim, KW and Kim, JYH and Choi, TY and Yang, SH and Oh, CH and Kwon, KK and Kim, SJ}, title = {Euzebyella algicola sp. nov., a marine bacterium of the family Flavobacteriaceae, isolated from green algae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {764-768}, doi = {10.1099/ijsem.0.002581}, pmid = {29458477}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chlorophyta/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-negative, yellow-pigmented, non-flagellated, gliding, rod-shaped and aerobic bacterium, designated MEBiC 12267T, was isolated from green algae of Jeju Island. 16S rRNA gene sequence analysis revealed that the strain MEBiC 12267T was affiliated to the genus Euzebyella of the family Flavobacteriaceae and showed the highest similarity to Euzebyella marina KCTC 42440T (98.5 %). The DNA-DNA relatedness value of strain MEBiC 12267T with E. marina KCTC 42440T was 25 %. Growth was observed at 10-37 °C (optimum, 30-33 °C), at pH 6.0-9.5 (optimum, 8.0-8.5) and with 0.5-9.0 % (w/v) NaCl (optimum, 2.5-3.5 %). The predominant cellular fatty acids were iso-C15 : 0, iso-C15 : 1 G and iso-C17 : 0 3-OH. The major respiratory quinone was MK-6. Polar lipids included phosphatidylethanolamine, seven unidentified lipids and two unidentified aminolipids. The DNA G+C content was 40.7 mol%. On the basis of the data from the polyphasic taxonomic study, it was concluded that the strain MEBiC 12267T represents a novel species within the genus Euzebyella, for which the name Euzebyella algicola sp. nov. is proposed. The type strain of E. algicola is MEBiC 12267T (=KCCM 43264T=JCM 32170T).}, } @article {pmid29458476, year = {2018}, author = {Singh, H and Kaur, M and Kaur, L and Sharma, S and Mishra, S and Tanuku, NRS and Pinnaka, AK}, title = {Bacillus lacus sp. nov., isolated from a water sample of a salt lake in India.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002588}, pmid = {29458476}, issn = {1466-5034}, abstract = {A strictly aerobic, alkaliphilic, Gram-stain-positive, motile, rod-shaped bacterium, designated strain AK74T, was isolated from a water sample collected from Sambhar salt lake, Rajasthan, India. Colonies were circular, 1.2 mm in diameter, shiny, smooth, whitish and convex with an entire margin after 48 h growth at 37 °C with pH 9.0. Growth occurred at 25-42 °C, 0-4 % (w/v) NaCl and at a pH of 7-12. Strain AK74T was positive for aesculinase, caseinase, lipase activities and negative for oxidase, catalase, amylase, cellulase, DNase, gelatinase and urease activities. The fatty acids were dominated by branched iso-, anteiso- and saturated fatty acids with a high abundance of iso-C15 : 0, anteiso-C15 : 0, C16 : 0 and C16 : 1 and the cell-wall peptidoglycan contained meso-diaminopimelic acid as the diagnostic diamino acid. The DNA G+C content of strain AK74T was 51.6 mol%. A blast sequence similarity search based on 16S rRNA gene sequences indicated that Bacillus niabensis, Bacillus idriensisand Bacillus halosaccharovorans were the nearest phylogenetic neighbours, with a pair-wise sequence similarities of 96.6, 96.6 and 96.5%, respectively. Phylogenetic analysis showed that strain AK74T clustered with Bacillus mangrove and together clustered with Bacillus idriensisand Bacillus indicus. Based on its phenotypic characteristics and on phylogenetic inference, strain AK74T represents a novel species of the genus Bacillus, for which the name Bacilluslacus sp. nov. is proposed. The type strain is AK74T (=MTCC 12638T=KCTC 33946T=JCM 32185T).}, } @article {pmid29458475, year = {2018}, author = {Gan, L and Zhang, H and Long, X and Tian, J and Wang, Z and Zhang, Y and Dai, Y and Tian, Y}, title = {Ornithinibacillus salinisoli sp. nov., a moderately halophilic bacterium isolated from a saline-alkali soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {769-775}, doi = {10.1099/ijsem.0.002580}, pmid = {29458475}, issn = {1466-5034}, mesh = {Alkalies ; Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Salinity ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A taxonomic study was performed on strain LCB256T, which was isolated from a saline-alkali soil sample taken from northwestern China. Cells of strain LCB256T were Gram-stain-positive, aerobic, rod-shaped and grew at 3-17 % (w/v) NaCl (optimum 10-15 %), 10-52 °C (optimum 25-30 °C) and pH 7.0-9.0 (optimum 8.0). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain LCB256T was most closely related to the two genera of Ornithinibacillus and Oceanobacillus, showing highest sequence similarity to Oceanobacillus limi KCTC 13823T (97.8 %) and Ornithinibacillus bavariensis WSBC 24001T (97.2 %). The peptidoglycan amino acid type was found to be A4β and the major respiratory quinone was determined to be MK-7. The polar lipid profile of strain LCB256T contained diphosphatidylglycerol, phosphatidylglycerol, one unidentified phospholipid and two unidentified aminolipids. The dominant cellular fatty acids were anteiso-C15 : 0 and iso-C15 : 0. The G+C content of genomic DNA was 39.3 mol%. DNA-DNA relatedness values between strain LCB256T and Ornithinibacillus halophilus KCTC 13822T and Oceanobacillus limi KCTC 13823T were 46.2 and 34.8 %, respectively. Based on this polyphasic taxonomic study, a novel species of the genus Ornithinibacillus, Ornithinibacillussalinisoli sp. nov. is proposed. The type strain is LCB256T (=CGMCC 1.15809T=KCTC 33862T).}, } @article {pmid29458474, year = {2018}, author = {Ko, Y and Yim, J and Hwang, WM and Kang, K and Ahn, TY}, title = {Roseomonas fluminis sp. nov. isolated from sediment of a shallow stream.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {782-787}, doi = {10.1099/ijsem.0.002578}, pmid = {29458474}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Methylobacteriaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phosphatidylglycerols/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rivers/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {An aerobic, Gram-negative, motile by means of a single polar flagellum, and ovoid-shaped bacterium, designated D3T, was isolated from shallow stream sediments in Sinan-gun, South Korea. Growth occurred at 15-40 °C (optimum 35 °C), at pH 7.0-8.0 (optimum pH 7.0), and at an optimum NaCl concentration of 0.5 % (w/v). The major cellular fatty acids (>7 % of the total) were C16 : 0, C18 : 0 2-OH, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c). The predominant quinone was ubiquinone-10, and the G+C content of the genomic DNA of strain D3T was 73.1 mol%. The major polyamine was spermidine. The major polar lipids of the isolate were diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain D3T clustered with Roseomonas aquatica TR53T within the genus Roseomonas. The 16S rRNA gene sequence of strain D3T showed the highest sequence similarity to R. aquatica TR53T (95.9 %), followed by Roseomonas rosea 173-96T (95.7 %) and Roseomonas aerilata 5420S-30T (95.0 %). Based on the phenotypic, phylogenetic and chemotaxonomic characterization, strain D3T represents a novel species of the genus Roseomonas, for which the name Roseomonas fluminis sp. nov. is proposed. The type strain is D3T (=KACC 19269T=JCM 31968T).}, } @article {pmid29458473, year = {2018}, author = {Lee, DG and Trujillo, ME and Kang, S and Nam, JJ and Kim, YJ}, title = {Epidermidibacterium keratini gen. nov., sp. nov., a member of the family Sporichthyaceae, isolated from keratin epidermis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {745-750}, doi = {10.1099/ijsem.0.002579}, pmid = {29458473}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Epidermis/*microbiology ; Fatty Acids/chemistry ; Humans ; Keratinocytes/*microbiology ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel actinobacterial strain, designated EPI-7T, was isolated on R2A agar from human skin (keratinocytes) and subjected to a taxonomic study using a polyphasic approach. Strain EPI-7T showed a Gram-positive reaction, was non-motile, non-spore-forming, and cells had a rod-shape. Colonies were round, convex and pale yellow. Phylogenetic analysis based on 16S rRNA gene sequences showed that the novel isolate formed a cluster with several uncultured bacterial clones and with cultured members of the genera Modestobacter and Sporichthya. The 16S rRNA gene sequence similarities with respect to the type strains of recognized species from the above genera and other phylogenetic neighbours ranged from 92.6 to 93.4 %. The G+C content of the genomic DNA was 68.9 mol%. The only isoprenoid quinone was MK-9(H4), and the major fatty acids detected were C17 : 1ω8c, C16 : 0, iso-C15 : 0 and summed feature 3. The major polar lipids were found to be phosphatidylethanolamine, phosphatidylinositol, three unidentified phospholipids, phosphatidylglycerol, phosphatidylcholine, two unidentified amino lipids and three unidentified lipids. The cell-wall peptidoglycan contained meso-diaminopimelic acid, glutamic acid and alanine. Whole-cell sugars present included rhamnose, glucose and galactose. The combination of the genotypic and phenotypic data allowed differentiation of strain EPI-7T from its closest phylogenetic neighbours and provided evidence that strain EPI-7T represents a novel genus and species in the family Sporichthyaceae. The name Epidermidibacterium keratini gen. nov., sp. nov. is proposed with the type strain being EPI-7T (=KCCM 90264T=JCM 31644T).}, } @article {pmid29458472, year = {2018}, author = {Hubka, V and Nováková, A and Jurjević, Ž and Sklenář, F and Frisvad, JC and Houbraken, J and Arendrup, MC and Jørgensen, KM and Siqueira, JPZ and Gené, J and Kolařík, M}, title = {Polyphasic data support the splitting of Aspergillus candidus into two species; proposal of Aspergillus dobrogensis sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {995-1011}, doi = {10.1099/ijsem.0.002583}, pmid = {29458472}, issn = {1466-5034}, mesh = {Antifungal Agents/pharmacology ; Aspergillus/*classification/drug effects ; Bayes Theorem ; DNA, Fungal/genetics ; Microbial Sensitivity Tests ; Mycological Typing Techniques ; Phenotype ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Aspergillus candidus is a species frequently isolated from stored grain, food, indoor environments, soil and occasionally also from clinical material. Recent bioprospecting studies highlighted the potential of using A. candidus and its relatives in various industrial sectors as a result of their significant production of enzymes and bioactive compounds. A high genetic variability was observed among A. candidus isolates originating from various European countries and the USA, that were mostly isolated from indoor environments, caves and clinical material. The A. candidus sensu lato isolates were characterized by DNA sequencing of four genetic loci, and agreement between molecular species delimitation results, morphological characters and exometabolite spectra were studied. Classical phylogenetic methods (maximum likelihood, Bayesian inference) and species delimitation methods based on the multispecies coalescent model supported recognition of up to three species in A. candidus sensu lato. After evaluation of phenotypic data, a broader species concept was adopted, and only one new species, Aspergillus dobrogensis, was proposed. This species is represented by 22 strains originating from seven countries (ex-type strain CCF 4651T=NRRL 62821T=IBT 32697T=CBS 143370T) and its differentiation from A. candidus is relevant for bioprospecting studies because these species have different exometabolite profiles. Evaluation of the antifungal susceptibility of section Candidi members to six antifungals using the reference EUCAST method showed that all species have low minimum inhibitory concentrations for all tested antifungals. These results suggest applicability of a wide spectrum of antifungal agents for treatment of infections caused by species from section Candidi.}, } @article {pmid29458471, year = {2018}, author = {Schellenberg, J and Busse, HJ and Hardt, M and Schubert, P and Wilke, T and Kämpfer, P and Glaeser, SP}, title = {Proposal of Litorimonas haliclonae sp. nov., isolated from a marine sponge of the genus Haliclona.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {835-843}, doi = {10.1099/ijsem.0.002592}, pmid = {29458471}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Germany ; Haliclona/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/chemistry ; Ubiquinone/chemistry ; }, abstract = {A bright-orange-pigmented, Gram-stain-negative, motile, and rod-shaped bacterium, strain MAA42T, was isolated from a marine sponge of the genus Haliclona, which is in long-time culture in a marine aquarium system at the Justus Liebig University Giessen, Germany. The strain grew at 4-34 °C (optimum 28 °C), in the presence of 0.5-9.5 % (w/v) NaCl (optimum 3.5 %) and at pH 4.5-10.0 (optimum pH 7.5). Strain MAA42T shared the highest 16S rRNA gene sequence similarity (98.1 %) with the type strain of Litorimonas taeanensis. Sequence similarities to all other closely related type strains were below 97 %. DNA-DNA hybridization of strain MAA42T with L. taeanensis DSM 22008T resulted in values of 4.7 % (reciprocal 17.7 %). Major cellular fatty acids of strain MAA42T were C18 : 1ω7c (66.2 %), C18 : 1 2-OH (17.4 %), and C18 : 0 (14.1 %). Spermidine was predominant in the polyamine pattern, and ubiquinone Q-10 was the major respiratory quinone. The polar lipid profile contained the major compounds phosphatidylglycerol, monoglycosyldiglyceride, three unidentified phospholipids, and one unidentified glycolipid. Glucuronopyranosyldiglyceride was present as a minor compound. The diagnostic diamino acid of the peptidoglycan was meso-diaminopimelic acid. The genomic DNA G+C content was 52.8 mol%. Based on the genotypic, chemotaxonomic, and phenotypic analyses, strain MAA42T represents a novel species of the genus Litorimonas, for which the name Litorimonas haliclonae is proposed. The type strain is MAA42T (=CCM 8709T=CIP 111178T=LMG 29765T).}, } @article {pmid29458470, year = {2018}, author = {Ren, Q and Yu, M and Li, Y and Zhang, Y and Shi, X and Wu, Y and Su, Y and Wang, Y and Wang, X and Zhang, XH}, title = {Flavobacterium ovatum sp. nov., a marine bacterium isolated from an Antarctic intertidal sandy beach.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {795-800}, doi = {10.1099/ijsem.0.002586}, pmid = {29458470}, issn = {1466-5034}, mesh = {Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Silicon Dioxide ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A rod-shaped, Gram-staining-negative, strictly aerobic, non-motile bacterium with no flexirubin-type pigment, designated as W201ET, was isolated from an intertidal sandy beach in Antarctica. The organism formed faintly yellow, round colonies on marine agar 2216E. The strain required sea salts for growth and grew optimally in the presence of 2 % (w/v) NaCl at pH 7.0, 20 °C. Phylogenetic analysis based on 16S rRNA gene sequence indicated that strain W201ET belonged to the genus Flavobacterium and showed the highest sequence similarity to Flavobacterium algicola NBRC 102673T (96.5 %). The major respiratory quinone was menaquinone 6, and the predominant fatty acids were iso-C15 : 1 G, iso-C15 : 0, iso-C15 : 0 3-OH and summed feature 3 (which comprises C16 : 1ω7c and/or C16 : 1ω6c). The polar lipids of strain W201ET comprised one phosphatidylethanolamine, two unidentified aminolipids and three unidentified polar lipids. The DNA G+C content of strain W201ET was 34.1 mol%. On the basis of the polyphasic analyses, this isolate was considered to represent a novel species in the genus Flavobacterium, for which the name Flavobacterium ovatum sp. nov. is proposed. The type strain is W201ET (=KCTC 52693T=MCCC 1K03251T=CGMCC 1.16053T).}, } @article {pmid29458469, year = {2018}, author = {Cai, H and Cui, H and Zeng, Y and An, M and Jiang, H}, title = {Sandarakinorhabdus cyanobacteriorum sp. nov., a novel bacterium isolated from cyanobacterial aggregates in a eutrophic lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {730-735}, doi = {10.1099/ijsem.0.002571}, pmid = {29458469}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Cyanobacteria ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sphingomonadaceae/*classification/genetics/isolation & purification ; Ubiquinone/chemistry ; }, abstract = {A bacterial strain, designated TH057T, was isolated from cyanobacterial aggregates in a eutrophic lake in China. Cells were observed to be slightly curved, rod-shaped, capsule-forming and stained Gram-negative. Optimal growth was obtained at pH 7.0 (range: pH 5-9) and 30 °C (range: 20-37 °C) in R2A broth. According to the absorption spectrum, carotenoids (455 and 490 nm) and light-harvesting complex LHI (857 nm) were present in the cells. The cells were found to be positive for oxidase and catalase activities. The major respiratory quinone was ubiquinone Q-10. The major fatty acids were identified as C17 : 1ω6c, C16 : 1ω7c/C16 : 1ω6c, C18 : 1ω6c/C18 : 1ω7c and C16 : 0. The major polar lipids were found to consist of phosphatidylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, unidentified glycolipid and two sphingoglycolipids. Strain TH057T shared highest 16S rRNA gene sequence similarity to Sandarakinorhabdus limnophila so42T (96.8 %), followed by Polymorphobacter fuscus D40PT (95.8 %). The genomic G+C content of strain TH057T was 66.1 mol% based on total genome calculations. The average nucleotide identity and the digital DNA-DNA hybridization value for the complete genomes were 81.0 and 23.0 % between strain TH057T and Sandarakinorhabdus limnophila so42T. The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis suggested that strain TH057T represents a novel species within the genus Sandarakinorhabdus, for which the name Sandarakinorhabduscyanobacteriorum sp. nov. is proposed. The type strain is TH057T (=CGMCC 1.15803T=LMG 30294T).}, } @article {pmid29458468, year = {2018}, author = {Choi, KD and Lee, GE and Park, JS}, title = {Aquimarina spongiicola sp. nov., isolated from spongin.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {990-994}, doi = {10.1099/ijsem.0.002575}, pmid = {29458468}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; Porifera/*microbiology ; RNA, Ribosomal, 16S/genetics ; Seawater/microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-reaction-negative, aerobic, motile by gliding, non-spore-forming, rod-shaped bacterial strain, designated 122CH820-2T, was isolated from spongin. This bacterium was characterized to determine its taxonomic position by using a polyphasic approach. Strain 122CH820-2T grew well at 25-30 °C on marine agar. On the basis of 16S rRNA gene sequence similarity, strain 122CH820-2T belonged to the family Flavobacteriaceae and was closely related to Aquimarina mytili PSC33T (96.8 % sequence similarity) and A. penaei P3-1T (96.7 %). Lower sequence similarities (<96.5 %) were found with all of the other recognized members of the genus Aquimarina. The G+C content of the genomic DNA was 35.2 mol%. The major respiratory quinone was menaquinone MK-6 and the major fatty acids were C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1 G and iso-C15 : 0 3-OH. The polar lipids were phosphatidylethanolamine, one aminophospholipid and five unidentified polar lipids. Strain 122CH820-2T could be differentiated genotypically and phenotypically from recognized species of the genus Aquimarina. The isolate therefore represents a novel species, for which the name Aquimarina spongiicola sp. nov. is proposed, with the type strain 122CH820-2T (=KACC 19274T=LMG 30078T).}, } @article {pmid29458467, year = {2018}, author = {Chaudhary, DK and Kim, J}, title = {Chitinophaga humicola sp. nov., isolated from oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {751-757}, doi = {10.1099/ijsem.0.002577}, pmid = {29458467}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Environmental Pollution ; Fatty Acids/chemistry ; Nepal ; Nucleic Acid Hybridization ; *Petroleum Pollution ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A yellow-coloured, Gram-stain-negative, non-motile, aerobic and rod-shaped bacterium, designated strain Ktm-2T, was isolated from oil-contaminated soil. Strain Ktm-2T was able to grow at 15 to 40 °C, pH 4.5-10.0 and 0-2 % (w/v) NaCl concentration. This strain was taxonomically characterized by a polyphasic approach. Based on the 16S rRNA gene sequence analysis, strain Ktm-2T represented a member of the genus Chitinophaga and shared highest sequence similarity with Chitinophaga barathri YLT18T (98.1 %), Chitinophaga cymbidii R156-2T (96.4 %) and Chitinophaga niabensis JS13-10T (96.3 %). The only respiratory quinone was menaqunone-7, the major polar lipid was phosphatidylethanolamine and the predominant fatty acids were iso-C15 : 0, C16 : 1ω5c and iso-C17 : 0 3-OH. The DNA G+C content was 52.1 mol%. The DNA-DNA relatedness between strain Ktm-2T and C. barathri YLT18T was 22.0 %, which falls below the threshold value of 70 % for the strain to be considered a novel species. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain Ktm-2T represents a novel species of the genus Chitinophaga, for which the name Chitinophagahumicola sp. nov. is proposed. The type strain is Ktm-2T (=KEMB 9005-693T=KACC 19388T=JCM 32158T).}, } @article {pmid29458466, year = {2018}, author = {Kim, DU and Lee, H and Lee, S and Park, S and Yoon, JH and Zhao, L and Kim, MK and Ahn, JH and Ka, JO}, title = {Deinococcus aluminii sp. nov., isolated from an automobile air conditioning system.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1099/ijsem.0.002574}, pmid = {29458466}, issn = {1466-5034}, abstract = {A Gram-stain-positive and pale pink-pigmented bacterial strain, designated ID0501T, was isolated from an automobile evaporator core collected in the Republic of Korea. The cells were aerobic and coccoidal. The strain grew at 15-40 ˚C (optimum, 37 ˚C), at pH 6.0-7.0 (optimum, pH 6.5), and in the presence of 0-1.5 % (w/v) NaCl. Phylogenetically, the strain was related to members of the genus Deinococcus and showed the highest sequence similarity, of 96.9 %, with Deinococcus metallilatus MA1002T. The major fatty acids of the strain were iso-C17 : 0, iso-C15 : 0 and iso-C13 : 0. The predominant respiratory quinone was MK-8. The polar lipids profile revealed the presence of phosphatidylethanolamine, phosphatidylglycerol, phosphatidylcholine, diphosphatidylglycerol, unidentified phospholipids, an unidentified aminolipid and unidentified glycolipids. The DNA G+C content of the strain was 68.3 mol%. On the basis of phenotypic, genotypic and chemotaxonomic data, strain ID0501T represents a novel species of the genus Deinococcus, for which the name Deinococcusaluminii sp. nov. (=KACC 19286T=NBRC 112889T) is proposed.}, } @article {pmid29458465, year = {2018}, author = {Kukolya, J and Bata-Vidács, I and Luzics, S and Tóth, E and Kéki, Z and Schumann, P and Táncsics, A and Nagy, I and Olasz, F and Tóth, Á}, title = {Xylanibacillus composti gen. nov., sp. nov., isolated from compost.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {698-702}, doi = {10.1099/ijsem.0.002523}, pmid = {29458465}, issn = {1466-5034}, mesh = {Bacillales/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; *Composting ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-positive bacterial strain, designated as K13T, was isolated from compost and characterized using a polyphasic approach to determine its taxonomic position. On the basis of 16S rRNA gene sequence analysis, the strain showed highest similarity (93.8 %) to Paenibacillus nanensis MX2-3T. Cells of strain K13T were aerobic, motile rods. The major fatty acids were anteiso C15 : 0 (34.4 %), iso C16 : 0 (17.3 %) and C16 : 0 (10.0 %). The major menaquinone was MK-7, the polar lipid profile included diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phosphatidylserine and an aminophospholipid. The DNA G+C content was 52.3 %. Based on phenotypic, including chemotaxonomic characteristics and analysis of the 16S rRNA gene sequences, it was concluded that strain K13T represents a novel genus, for which the name Xylanibacillus gen. nov., sp. nov. is proposed. The type species of the genus is Xylanibacillus composti, the type strain of which is strain K13T (=DSM 29793T=NCAIM B.02605T).}, } @article {pmid29458464, year = {2018}, author = {Melo, LA and Ventura, JA and Costa, H and Kitajima, EW and Ferreira, J and Bedendo, IP}, title = {Delineation of a novel subgroup 16SrXIII-J phytoplasma, a 'Candidatus Phytoplasma hispanicum'-related strain, based on computer-simulated RFLP and phylogenetic analysis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {962-966}, doi = {10.1099/ijsem.0.002547}, pmid = {29458464}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Brazil ; DNA Primers ; DNA, Bacterial/genetics ; Fragaria/*microbiology ; *Phylogeny ; Phytoplasma/*classification ; Plant Diseases/*microbiology ; Polymerase Chain Reaction ; *Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Symptoms of fruit phyllody and slow growth, which are suggestive of phytoplasma infection, were observed in strawberry plants cultivated in commercial fields. In order to provide evidence of association of phytoplasma with affected plants, assays for detecting and identifying were performed through computer-simulated restriction fragment length polymorphism (RFLP) and phylogenetic analysis. Total DNA was extracted from symptomatic and asymptomatic samples and used as template in nested PCR primed by the primers P1/Tint followed by R16F2n/16R2. Amplified DNA fragments of 1.2 kb from the 16S rRNA gene revealed the presence of phytoplasma in all symptomatic samples. Molecular detection was confirmed by electron transmission microscopy, which evidenced pleomorphic bodies in the phloem vessels. Nucleotide sequence representative of the strawberry phytoplasma shared 97.2 to 99 % similarity with phytoplasmas currently classified as members of the distinct subgroups within the 16SrXIII group. Similarity coefficient (F) values ranged from 0.70 to 0.92, indicating that strawberry phytoplasma delineates a new strain in addition to 'Candidatus Phytoplasma hispanicum'-related strains. The evolutionary tree displayed that this strain emerges as a new branch in relation to those previously described. The novel strain, designated SFP (strawberry fruit phyllody) phytoplasma represents the new 16SrXIII-J subgroup and its sequence, denominated SFP-Br02, was deposited in the GenBank database (EU719108). These findings contribute for the knowledge of the genetic diversity existing among members of the group 16SrXIII and establishes strawberry as an additional host of representatives of this group in Brazil.}, } @article {pmid29458463, year = {2018}, author = {Albuquerque, L and Polónia, ARM and Barroso, C and Froufe, HJC and Lage, O and Lobo-da-Cunha, A and Egas, C and da Costa, MS}, title = {Raineya orbicola gen. nov., sp. nov. a slightly thermophilic bacterium of the phylum Bacteroidetes and the description of Raineyaceae fam. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {4}, pages = {982-989}, pmid = {29458463}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hot Springs/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Portugal ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An isolate, designated SPSPC-11T, with an optimum growth temperature of about 50 °C and an optimum pH for growth between 7.5 and 8.0, was recovered from a hot spring in central Portugal. Based on phylogenetic analysis of its 16S rRNA sequence, the new organism is most closely related to the species of the genus Thermonema but with a pairwise sequence similarity of <85 %. The isolate was orange-pigmented, formed non-motile long filaments and rod-shaped cells that stain Gram-negative. The organism was strictly aerobic, oxidase-positive and catalase-positive. The major fatty acids were iso-C15:0, iso-C15 : 0 2-OH and iso-C17 : 0 3-OH. The major polar lipids were one aminophospholipid, two aminolipids and three unidentified lipids. Menaquinone 7 was the major respiratory quinone. The DNA G+C content of strain SPSPC-11T was 37.6 mol% (draft genome sequence). The high quality draft genome sequence corroborated many of the phenotypic characteristics of strain SPSPC-11T. Based on genotypic, phylogenetic, physiological and biochemical characterization we describe a new species of a novel genus represented by strain SPSPC-11T (=CECT 9012T=LMG 29233T) for which we propose the name Raineya orbicola gen. nov., sp. nov. We also describe the family Raineyaceae to accommodate this new genus and species.}, } @article {pmid29458462, year = {2018}, author = {Wang, C and Huang, Y and Li, L and Guo, J and Wu, Z and Deng, Y and Dai, L and Ma, S}, title = {Lactobacillus panisapium sp. nov., from honeybee Apis cerana bee bread.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {703-708}, pmid = {29458462}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Bees/*microbiology ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Lactobacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; *Propolis ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A novel facultatively anaerobic, Gram-stain-positive, non-motile, non-spore-forming, catalase-negative bacterium of the genus Lactobacillus, designated strain Bb 2-3T, was isolated from bee bread of Apis cerana collected from a hive in Kunming, China. The strain was regular rod-shaped. Optimal growth occurred at 37 °C, pH 6.5 with 5.0 g l-1 NaCl. The predominant fatty acids were C18 : 1ω9c, C16 : 0 and C19 : 0 iso. Respiratory quinones were not detected. Seven glycolipids, three lipids, phosphatidylglycerol and diphosphatidylglycerol were detected. The peptidoglycan type A4α l-Lys-d-Asp was determined. Strain Bb 2-3T was closely related to Lactobacillus bombicola DSM 28793T, Lactobacillus apis LMG 26964T and Lactobacillus helsingborgensis DSM 26265T, with 97.8, 97.6 and 97.0 % 16S rRNA gene sequence similarity, respectively. A comparison of two housekeeping genes, rpoA and pheS, revealed that strain Bb 2-3T was well separated from the reference strains of species of the genus Lactobacillus. The average nucleotide identity between strain Bb 2-3T and the type strains of closely related species was lower than the 95-96 % threshold value for delineation of genomic prokaryotic species. The G+C content of the genomic DNA of strain Bb 2-3T was 37.4 mol%. On the basis of phenotypic, chemotaxonomic and phylogenetic analyses, strain Bb 2-3T is proposed to represent a novel species of the genus Lactobacillus, for which we propose the name Lactobacillus panisapium sp. nov. The type strain is Bb 2-3T (=DSM 102188T=ACCC 19955T).}, } @article {pmid29458461, year = {2018}, author = {Ben Ali Gam, Z and Thioye, A and Cayol, JL and Joseph, M and Fauque, G and Labat, M}, title = {Characterization of Desulfovibrio salinus sp. nov., a slightly halophilic sulfate-reducing bacterium isolated from a saline lake in Tunisia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {715-720}, doi = {10.1099/ijsem.0.002567}, pmid = {29458461}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Desulfovibrio/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Lakes/*microbiology ; Oxidation-Reduction ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; Sulfates/metabolism ; Tunisia ; }, abstract = {A novel slightly halophilic sulfate-reducing bacterium, designated strain P1BSRT, was isolated from water of a saline lake in Tunisia. Strain P1BSRT had motile (single polar flagellum), Gram-negative, rod-shaped, non-spore-forming cells, occurring singly or in pairs. Strain P1BSRT grew at temperatures between 15 and 45 °C (optimum 40 °C), and in a pH range between 6 and 8.5 (optimum pH 6.7). The strain required NaCl for growth (1 % w/v), and tolerated high NaCl concentration (up to 12 % w/v) with an optimum of 3 % (w/v). Sulfate, thiosulfate and sulfite served as terminal electron acceptors, but not elemental sulfur, fumarate, nitrate and nitrite. Strain P1BSRT utilized lactate, pyruvate, formate, d-fructose and glycerol as carbon and energy sources. The main cellular fatty acid was C16 : 0 (50.8 %). The genomic DNA G+C content was 47.7 mol%. Phylogenetic analysis of 16S rRNA gene sequence similarity indicated that strain P1BSRT was affiliated to the genus Desulfovibrio, with the type strains Desulfovibrio salexigens (96.51 %), Desulfovibrio zosterae (95.68 %), Desulfovibrio hydrothermalis (94.81 %) and Desulfovibrio ferrireducens (94.73 %) as its closest phylogenetic relatives. On the basis of genotypic, phenotypic and phylogenetic characteristics, it is proposed to assign strain P1BSRT to a novel species of the genus Desulfovibrio, Desulfovibrio salinus sp. nov. The type strain is P1BSRT (=DSM 101510T=JCM 31065T).}, } @article {pmid29458460, year = {2018}, author = {Li, AZ and Lin, LZ and Zhang, MX and Lv, Y and Zhu, HH}, title = {Arenibacter catalasegens sp. nov., isolated from marine surface sediment, and emended description of the genus Arenibacter.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {758-763}, doi = {10.1099/ijsem.0.002576}, pmid = {29458460}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Indian Ocean ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-staining-negative, aerobic, non-motile, rod-shaped bacterium, designated as P308H10T, was isolated from surface sediment of the Southern Indian Ocean. Growth occurred at 4-36 °C (optimum 20-25 °C), pH 6.0-8.5 (optimum 7.5-8.0) and in the presence of 1-8 % (w/v) NaCl (optimum 2-3 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain P308H10T lies within the clade of members of the genus Arenibacter and is closely related to Arenibacterhampyeongensis HP12T (98.0 %), Arenibacterechinorum KMM 6032T (98.4 %), Arenibacterpalladensis LMG 21972T (97.9 %), Arenibactertroitsensis KMM 3674T (97.9 %) and 'Arenibacter algicola' TG409 (98.1 %). The average nucleotide identity and digital DNA-DNA hybridization values between strain P308H10T and the five reference strains were 85.9-80.6 % and 30.2-23.6 %, respectively. The major fatty acids (>10 %) of strain P308H10T were summed feature 3, iso-C17 : 0 3-OH, iso-C15 : 1 G and iso-C15 : 0. The major polar lipids comprised phosphatidylethanolamine, five unidentified aminolipids and four unidentified lipids. The only respiratory quinone was menaquinone-6. The genomic DNA G+C content was 38.2 mol%. On the basis of the phenotypic, phylogenetic and chemotaxonomic data presented, strain P308H10T represents a novel species of the genus Arenibacter, for which the name Arenibacter catalasegens sp. nov. is proposed. The type strain is P308H10T (=GDMCC 1.1230T=KCTC 52983T). An emended description of the genus Arenibacter is also proposed.}, } @article {pmid29458459, year = {2018}, author = {Klotz, F and Brinkhoff, T and Freese, HM and Wietz, M and Teske, A and Simon, M and Giebel, HA}, title = {Tritonibacter horizontis gen. nov., sp. nov., a member of the Rhodobacteraceae, isolated from the Deepwater Horizon oil spill.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {736-744}, doi = {10.1099/ijsem.0.002573}, pmid = {29458459}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gulf of Mexico ; Heterotrophic Processes ; *Petroleum Pollution ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; Water Pollutants, Chemical ; }, abstract = {A heterotrophic, Gram-stain-negative, aerobic, sodium-requiring and motile bacterium was isolated from oil-contaminated surface water of the Gulf of Mexico during the Deepwater Horizon oil spill. Strain O3.65T showed highest 16S rRNA gene sequence similarity to Phaeobacter gallaeciensis BS107T and Phaeobacter inhibens T5T, both with 98.3 %, respectively. Based on complete genome analysis, highest similarity was observed to species of the genus Ruegeria. Strain O3.65T exhibited a broad salinity, temperature and pH range of 0.5-10 % NaCl, 4-45 °C and 5.5-9.0, respectively. The DNA G+C content of strain O3.65T was 61.5 mol%. The major respiratory lipoquinone was ubiquinone-10 (Q-10), the most dominant fatty acids (>1 %) comprised 18 : 1ω7c and 18 : 1ω7c 11-methyl, 10 : 0 3OH, 12 : 1 3OH, 14 : 1 3OH/3-oxo-14 : 0, 16 : 0, 16 : 0 2OH, 18 : 1 2OH and 12 : 1. The polar lipid pattern indicated presence of phosphatidylcholine, phosphatidylglycerol, an unidentified aminolipid, two unidentified phospholipids and seven unidentified lipids. On Difco marine broth agar, strain O3.65T formed smooth, shiny white to beige and convex colonies with regular edges. Phylogenetic, phylogenomic and phenotypic differences revealed that strain O3.65T represents a new species of a novel genus within the family Rhodobacteraceae, for which we propose the name Tritonibacter horizontis gen. nov., sp. nov. The type strain of the type species is O3.65T (=DSM 101689T=LMG 29740T).}, } @article {pmid29458458, year = {2018}, author = {Mohr, KI and Moradi, A and Glaeser, SP and Kämpfer, P and Gemperlein, K and Nübel, U and Schumann, P and Müller, R and Wink, J}, title = {Nannocystis konarekensis sp. nov., a novel myxobacterium from an Iranian desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {721-729}, doi = {10.1099/ijsem.0.002569}, pmid = {29458458}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Desert Climate ; Fatty Acids/chemistry ; Iran ; Myxococcales/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; }, abstract = {An orange-coloured myxobacterium, MNa11734T, was isolated from desert in Iran. MNa11734T had rod-shaped vegetative cells, moved by gliding and was bacteriolytic. No real fruiting body formation could be observed, but sporangioles were produced on water agar. The strain was mesophilic, strictly aerobic and chemoheterotrophic. 16S rRNA gene analyses revealed that MNa11734T belonged to the family Nannocystaceae, genus Nannocystis and was closely related to Nannocystis pusilla Na p29T (DSM 14622T) and Nannocystis exedens Na e1T (DSM 71T), with 97.8 and 97.6 % 16S rRNA gene sequence similarity, respectively. Laboratory-measured DNA-DNA hybridization showed only 9.5/15.7 % (reciprocal) similarity between the novel strain and N. pusilla Na p29T, and 14.1/20.4 % between the strain and N. exedens Na e1T, whereas DNA-DNA hybridization estimates derived from draft genome sequences were 21.8-23.0 % and 22.2-23.7 %, respectively, depending on the calculation method. The G+C content of DNA from Nannocystis konarekensis MNa11734T was 73.3 mol%, for N. pusilla Nap29T it was 71.8 mol% and for N. exedens Nae1T it was 72.2 mol%. The major fatty acids of the new strain were C16 : 1 (56.2 %), iso-C17 : 0 (14.4 %), C14 : 0 (8.2 %), C16 : 0 (6.6 %) and iso-C15 : 0 (5.9 %). Strain MNa11734T exhibited phylogenetic and physiological similarities to the two other species of Nannocystis, i.e. N. pusilla and N. exedens, but the differences were sufficient enough to represent a novel species, for which the name Nannocystiskonarekensis sp. nov. is proposed. The type strain is MNa11734T (=DSM 104509T=NCCB 100618T).}, } @article {pmid29458457, year = {2018}, author = {Dahal, RH and Kim, J}, title = {Brevundimonas humi sp. nov., an alphaproteobacterium isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {3}, pages = {709-714}, doi = {10.1099/ijsem.0.002559}, pmid = {29458457}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Caulobacteraceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {During a study of bacterial diversity of soil, a novel strain, CA-15T, was isolated from Kyonggi University forest soil. Cells were aerobic, Gram-stain-negative, motile, non-spore-forming, rod-shaped, oxidase-positive and catalase- negative. Tyrosine was not oxidized but produced red pigmentation on an agar palte. Strain CA-15T hydrolysed Tween 60 and DNA. It grew at 15-35 °C (optimum, 25-30 °C), pH 6.0-10.0 (optimum, 7.0-9.0) and at 1.5 % (w/v) NaCl concentration. Phylogenetic analysis based on its 16S rRNA gene sequence indicated that strain CA-15T formed a lineage within the family Caulobacteraceae of the class Alphaproteobacteria that was distinct from various species of the genus Brevundimonas. Brevundimonas bullata DSM 7126T was the closest member of strain CA-15T on the basis of 16S rRNA gene sequence similarity (98.48 %). Q-10 was only an isoprenoid quinone detected for strain CA-15T. The major polar lipids were 1,2-di-O-acyl-3-O-[d-glucopyranosyl-(1→4)-αd-glucopyranuronosyl]glycerol, 1,2-di-O-acyl-3-O-[αd-glucopyranosyl]-sn-glycerol, 1,2-di-O-acyl-3-O-αd-glucopyranuronosylglycerol, 1,2-diacyl-3-O-[6'-phosphatidyl-αd-glucopyranosyl]glycerol and phosphatidylglycerol. The major cellular fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0, C18 : 1ω7c 11-methyl and C17 : 1ω8c. The DNA G+C content of strain CA-15T was 63.6 mol%. The polyphasic characterization indicated that strain CA-15T represents a novel species in the genus Brevundimonas, for which the name Brevundimonas humi sp. nov. is proposed. The type strain of Brevundimonas humi is CA-15T (=KEMB 9005-528T=KACC 19106T=NBRC 112677T).}, } @article {pmid29458440, year = {2018}, author = {Phoolcharoen, N and Kantathavorn, N and Krisorakun, W and Sricharunrat, T and Teerayathanakul, N and Taepisitpong, C and Sornsamdang, G and Krongthong, W and Saeloo, S}, title = {Agreement of self- and physician-collected samples for detection of high-risk human papillomavirus infections in women attending a colposcopy clinic in Thailand.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {136}, pmid = {29458440}, issn = {1756-0500}, mesh = {Adult ; Aged ; Colposcopy ; Female ; Humans ; Middle Aged ; Papillomaviridae/*isolation & purification ; Papillomavirus Infections/*diagnosis ; Physicians/*standards ; Self-Examination/*standards ; Specimen Handling/*standards ; Thailand ; Uterine Cervical Neoplasms/*diagnosis ; }, abstract = {OBJECTIVE: To study the concordance between vaginal self- and endocervical physician-collected high-risk (hr) HPV testing in Thai women who attended a colposcopy clinic. Vaginal samples were obtained by self-sampling with a dry brush before endocervical samples were obtained by physicians. Both specimens were analyzed for hrHPV by Cobas4800 HPV test.

RESULTS: Of the 247 pairs of samples, overall hrHPV prevalence from self- and physician-collected samples was 41.3 and 36.0%, respectively. The overall agreement between the methods was 74.5% with κ 0.46 (P < 0.001). Our study revealed moderate agreement between self- and physician-collected methods for hrHPV testing.}, } @article {pmid29458438, year = {2018}, author = {Ediriweera, DS and Dilina, N and Saparamadu, V and Fernando, I and Kurukulasuriya, B and Fernando, D and Kurera, J}, title = {Aspirin is associated with low oral pH levels and antacid helps to increase oral pH.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {137}, pmid = {29458438}, issn = {1756-0500}, mesh = {Aged ; Antacids/*pharmacology ; Anti-Inflammatory Agents, Non-Steroidal/*adverse effects ; Aspirin/*adverse effects ; Cardiovascular Diseases/*prevention & control ; Female ; Humans ; Hydrogen-Ion Concentration/*drug effects ; Male ; Middle Aged ; Mouth/*chemistry/*drug effects ; }, abstract = {OBJECTIVE: Aspirin is a commonly used medicine for primary and secondary prevention of cardiovascular diseases. It is an acidic medicine associated with gastric irritation and acid reflux, which in turn can lead to low oral pH levels. Therefore, it is important to understand the association between aspirin and oral pH levels in order to achieve an optimum oral health condition among patients who take aspirin on prescription.

RESULTS: Out of 373 patients, 162 (44%) were males and 245 (66%) were on aspirin. 71% of aspirin taking patients and 29% of non-aspirin taking patients had oral pH less than 6.5 (P < 0.01). Aspirin showed a significant association with low oral pH levels (odds ratio = 1.91, 95% CI 1.23-2.99, P < 0.01). 78 patients were given antacids and followed up for 4 weeks, 63 of them (81%) showed an improvement in oral pH and the improvement was marked in the group who had oral pH between 5.5-6.0 compared to the group who had oral pH between 6.0-6.5 (P = 0.03). The results show that aspirin therapy is associated with low oral pH and administration of an antacid with aspirin helps to increase the oral pH level.}, } @article {pmid29458435, year = {2018}, author = {Jansen, RB and Møller Christensen, T and Bülow, J and Rørdam, L and Holstein, PE and Lander Svendsen, O}, title = {Long-term effects on the progress of neuropathy after diabetic Charcot foot: an 8.5-year prospective case-control study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {140}, pmid = {29458435}, issn = {1756-0500}, mesh = {Aged ; Case-Control Studies ; Diabetic Foot/*physiopathology ; Diabetic Nephropathies/*physiopathology ; *Disease Progression ; Female ; Follow-Up Studies ; Humans ; Male ; Middle Aged ; }, abstract = {OBJECTIVE: Charcot foot is a severe complication to diabetes mellitus, associated with diabetic neuropathy. Any long-term effects of a Charcot foot on the progress of neuropathy are still largely unexplored. The objective was to investigate whether a previous Charcot foot had any long-term effects on the progress of neuropathy.

RESULTS: An 8.5-year follow-up case-control study of 49 individuals with diabetes mellitus, 24 of whom also had Charcot foot at baseline visit in 2005-2007. Neuropathy was assessed with a questionnaire, biothesiometry, heart rate variability and venous occlusion plethysmography. Of the 49 baseline participants, 22 were able to participate in the follow-up. Twelve had passed away in the meantime. Heart rate variability was unchanged in both groups; from 9.7 to 7.2 beats/min (p = 0.053) in the Charcot group, and 14.3 to 12.6 beats/min (p = 0.762) in the control group. Somato-sensoric neuropathy showed no difference between baseline and follow-up in the Charcot group (from 39.1 to 38.5 V) (p = 0.946), but a significantly worsened sensitivity in the control group (from 25.1 to 38.9 V) (p = 0.002). In conclusion, we found that any differences in somatic or cardial autonomic neuropathy present at baseline had disappeared at follow-up after 8.5 years.}, } @article {pmid29458427, year = {2018}, author = {Aiewsakun, P and Simmonds, P}, title = {The genomic underpinnings of eukaryotic virus taxonomy: creating a sequence-based framework for family-level virus classification.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {38}, pmid = {29458427}, issn = {2049-2618}, support = {WT108418AIA//Wellcome Trust/United Kingdom ; }, mesh = {Eukaryota/*virology ; Evolution, Molecular ; Genome, Viral/*genetics ; Host Specificity/genetics ; Metagenomics ; Viruses/*classification/*genetics ; }, abstract = {BACKGROUND: The International Committee on Taxonomy of Viruses (ICTV) classifies viruses into families, genera and species and provides a regulated system for their nomenclature that is universally used in virus descriptions. Virus taxonomic assignments have traditionally been based upon virus phenotypic properties such as host range, virion morphology and replication mechanisms, particularly at family level. However, gene sequence comparisons provide a clearer guide to their evolutionary relationships and provide the only information that may guide the incorporation of viruses detected in environmental (metagenomic) studies that lack any phenotypic data.

RESULTS: The current study sought to determine whether the existing virus taxonomy could be reproduced by examination of genetic relationships through the extraction of protein-coding gene signatures and genome organisational features. We found large-scale consistency between genetic relationships and taxonomic assignments for viruses of all genome configurations and genome sizes. The analysis pipeline that we have called 'Genome Relationships Applied to Virus Taxonomy' (GRAViTy) was highly effective at reproducing the current assignments of viruses at family level as well as inter-family groupings into orders. Its ability to correctly differentiate assigned viruses from unassigned viruses, and classify them into the correct taxonomic group, was evaluated by threefold cross-validation technique. This predicted family membership of eukaryotic viruses with close to 100% accuracy and specificity potentially enabling the algorithm to predict assignments for the vast corpus of metagenomic sequences consistently with ICTV taxonomy rules. In an evaluation run of GRAViTy, over one half (460/921) of (near)-complete genome sequences from several large published metagenomic eukaryotic virus datasets were assigned to 127 novel family-level groupings. If corroborated by other analysis methods, these would potentially more than double the number of eukaryotic virus families in the ICTV taxonomy.

CONCLUSIONS: A rapid and objective means to explore metagenomic viral diversity and make informed recommendations for their assignments at each taxonomic layer is essential. GRAViTy provides one means to make rule-based assignments at family and order levels in a manner that preserves the integrity and underlying organisational principles of the current ICTV taxonomy framework. Such methods are increasingly required as the vast virosphere is explored.}, } @article {pmid29458422, year = {2018}, author = {Häsler, R and Kautz, C and Rehman, A and Podschun, R and Gassling, V and Brzoska, P and Sherlock, J and Gräsner, JT and Hoppenstedt, G and Schubert, S and Ferlinz, A and Lieb, W and Laudes, M and Heinsen, FA and Scholz, J and Harmsen, D and Franke, A and Eisend, S and Kunze, T and Fickenscher, H and Ott, S and Rosenstiel, P and Schreiber, S}, title = {The antibiotic resistome and microbiota landscape of refugees from Syria, Iraq and Afghanistan in Germany.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {37}, pmid = {29458422}, issn = {2049-2618}, support = {EXC306//Deutsche Forschungsgemeinschaft/International ; CRC1182 C2//Deutsche Forschungsgemeinschaft/International ; SysINFLAME CP3/4//Bundesministerium für Forschung und Technologie/International ; }, mesh = {Afghanistan ; *Bacteria/drug effects/genetics/isolation & purification ; Drug Resistance, Multiple, Bacterial/*genetics ; Feces/microbiology ; Germany ; Humans ; Iraq ; Microbiota/drug effects/genetics ; RNA, Ribosomal, 16S/genetics ; Refugees/*statistics & numerical data ; Syria ; }, abstract = {BACKGROUND: Multidrug-resistant bacteria represent a substantial global burden for human health, potentially fuelled by migration waves: in 2015, 476,649 refugees applied for asylum in Germany mostly as a result of the Syrian crisis. In Arabic countries, multiresistant bacteria cause significant problems for healthcare systems. Currently, no data exist describing antibiotic resistances in healthy refugees. Here, we assess the microbial landscape and presence of antibiotic resistance genes (ARGs) in refugees and German controls. To achieve this, a systematic study was conducted in 500 consecutive refugees, mainly from Syria, Iraq, and Afghanistan and 100 German controls. Stool samples were subjected to PCR-based quantification of 42 most relevant ARGs, 16S ribosomal RNA gene sequencing-based microbiota analysis, and culture-based validation of multidrug-resistant microorganisms.

RESULTS: The fecal microbiota of refugees is substantially different from that of resident Germans. Three categories of resistance profiles were found: (i) ARGs independent of geographic origin of individuals comprising BIL/LAT/CMA, ErmB, and mefE; (ii) vanB with a high prevalence in Germany; and (iii) ARGs showing substantially increased prevalences in refugees comprising CTX-M group 1, SHV, vanC1, OXA-1, and QnrB. The majority of refugees carried five or more ARGs while the majority of German controls carried three or less ARGs, although the observed ARGs occurred independent of signatures of potential pathogens.

CONCLUSIONS: Our results, for the first time, assess antibiotic resistance genes in refugees and demonstrate a substantially increased prevalence for most resistances compared to German controls. The antibiotic resistome in refugees may thus require particular attention in the healthcare system of host countries.}, } @article {pmid29458413, year = {2018}, author = {Olivares, M and Walker, AW and Capilla, A and Benítez-Páez, A and Palau, F and Parkhill, J and Castillejo, G and Sanz, Y}, title = {Gut microbiota trajectory in early life may predict development of celiac disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {36}, pmid = {29458413}, issn = {2049-2618}, support = {AGL2014-52101-P//Ministerio de Economía y Competitividad/International ; AGL2011-25169//Ministerio de Economía y Competitividad/International ; 613979 (MyNewGut)//Seventh Framework Programme/International ; AGL2007-66126-C03-03/ALI//Ministerio de Economía y Competitividad/International ; Grant 098051//Wellcome Trust/United Kingdom ; }, mesh = {Bifidobacterium/genetics/*isolation & purification ; Case-Control Studies ; Celiac Disease/*microbiology ; Child, Preschool ; Enterococcus/genetics/*isolation & purification ; Feces/microbiology ; Female ; Firmicutes/genetics/*isolation & purification ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Infant, Newborn ; Male ; Prospective Studies ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: To investigate whether alterations in the developing intestinal microbiota and immune markers precede celiac disease (CD) onset in infants at familial risk of developing the disease.

METHODS: A nested case-control study was carried out as part of a larger prospective cohort study, which included healthy full-term newborns (> 200) with at least one first relative with biopsy-verified CD. The present study includes cases of CD (n = 10) and the best-matched controls (n = 10) who did not develop the disease after 5-year follow-up. Fecal microbiota, assessed by high-throughput 16S rRNA gene amplicon sequencing, and immune parameters were profiled at 4 and 6 months of age and related to CD onset.

RESULTS: The microbiota of infants who remained healthy showed an increase in bacterial diversity over time, characterized by increases in Firmicutes families, but not those who developed CD. Infants who subsequently developed CD showed a significant reduction in sIgA levels over time, while those who remained healthy showed increases in TNF-α correlated to Bifidobacterium spp. An increased relative abundance of Bifidobacterium longum was associated with control children while increased proportions of Bifidobacterium breve and Enterococcus spp. were associated with CD development.

CONCLUSION: The findings suggest that alterations in the early trajectory of gut microbiota in infants at CD risk could influence the immune maturation process and predispose to CD, although larger population studies are warranted to confirm this hypothesis.}, } @article {pmid29458410, year = {2018}, author = {Tompkins, VS and Valverde, DP and Moss, WN}, title = {Human regulatory proteins associate with non-coding RNAs from the EBV IR1 region.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {139}, pmid = {29458410}, issn = {1756-0500}, support = {R00 GM112877/GM/NIGMS NIH HHS/United States ; 4R00GM112877-02//National Institute of General Medical Sciences (US)/ ; startup funds//Roy J. Carver Charitable Trust/ ; }, mesh = {*ELAV-Like Protein 1/genetics ; *Herpesvirus 4, Human/genetics ; *Heterogeneous Nuclear Ribonucleoprotein A1/genetics ; *Heterogeneous-Nuclear Ribonucleoprotein Group C/genetics ; Humans ; *Introns/genetics ; *RNA, Untranslated/genetics ; *RNA, Viral/genetics ; *RNA-Binding Proteins/genetics ; *Ribonucleoproteins/genetics ; }, abstract = {OBJECTIVE: The function of Epstein-Barr virus (EBV) stable intronic sequence (sis)RNAs, non-coding RNAs transcribed from a region required for EBV-mediated cellular transformation, remain unknown. To better understand the function of ebv-sisRNA-1 and ebv-sisRNA-2 from the internal repeat (IR)1 region of EBV, we used a combination of bioinformatics and biochemistry to identify associated RNA binding proteins. The findings reported here are part of ongoing studies to determine the functions of non-coding RNAs from the IR1 region of EBV.

RESULTS: Human regulatory proteins HNRNPA1 (heterogeneous nuclear ribonucleoprotein A1), HNRNPC, HNRNPL, HuR (human antigen R), and protein LIN28A (lin-28 homolog A) were predicted to bind ebv-sisRNA-1 and/or ebv-sisRNA-2; FUS (fused in sarcoma) was predicted to associate with ebv-sisRNA-2. Protein interactions were validated using a combination of RNA immunoprecipitation and biotin pulldown assays. Both sisRNAs also precipitated with HNRNPD and NONO (non-POU domain-containing octamer-binding protein). Interestingly, each of these interacting proteins also precipitated non-spliced non-coding RNA sequences transcribed from the IR1 region. Our findings suggest interesting roles for sisRNAs (through their interactions with regulatory proteins) and provide further evidence for the existence of non-spliced stable non-coding RNAs.}, } @article {pmid29458354, year = {2018}, author = {Puterova, J and Kubat, Z and Kejnovsky, E and Jesionek, W and Cizkova, J and Vyskot, B and Hobza, R}, title = {The slowdown of Y chromosome expansion in dioecious Silene latifolia due to DNA loss and male-specific silencing of retrotransposons.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {153}, pmid = {29458354}, issn = {1471-2164}, support = {15-21523Y//Grantová Agentura České Republiky/International ; FIT-S-17-3964//Vysoké Učení Technické v Brně/International ; }, mesh = {Base Composition ; Chromosome Mapping ; *Chromosomes, Plant ; DNA Copy Number Variations ; *DNA, Plant ; *Evolution, Molecular ; *Gene Silencing ; Genome Size ; Genome, Plant ; In Situ Hybridization, Fluorescence ; Repetitive Sequences, Nucleic Acid ; *Retroelements ; *Sequence Deletion ; Silene/classification/*genetics ; Terminal Repeat Sequences ; }, abstract = {BACKGROUND: The rise and fall of the Y chromosome was demonstrated in animals but plants often possess the large evolutionarily young Y chromosome that is thought has expanded recently. Break-even points dividing expansion and shrinkage phase of plant Y chromosome evolution are still to be determined. To assess the size dynamics of the Y chromosome, we studied intraspecific genome size variation and genome composition of male and female individuals in a dioecious plant Silene latifolia, a well-established model for sex-chromosomes evolution.

RESULTS: Our genome size data are the first to demonstrate that regardless of intraspecific genome size variation, Y chromosome has retained its size in S. latifolia. Bioinformatics study of genome composition showed that constancy of Y chromosome size was caused by Y chromosome DNA loss and the female-specific proliferation of recently active dominant retrotransposons. We show that several families of retrotransposons have contributed to genome size variation but not to Y chromosome size change.

CONCLUSIONS: Our results suggest that the large Y chromosome of S. latifolia has slowed down or stopped its expansion. Female-specific proliferation of retrotransposons, enlarging the genome with exception of the Y chromosome, was probably caused by silencing of highly active retrotransposons in males and represents an adaptive mechanism to suppress degenerative processes in the haploid stage. Sex specific silencing of transposons might be widespread in plants but hidden in traditional hermaphroditic model plants.}, } @article {pmid29458351, year = {2018}, author = {Russo, PST and Ferreira, GR and Cardozo, LE and Bürger, MC and Arias-Carrasco, R and Maruyama, SR and Hirata, TDC and Lima, DS and Passos, FM and Fukutani, KF and Lever, M and Silva, JS and Maracaja-Coutinho, V and Nakaya, HI}, title = {CEMiTool: a Bioconductor package for performing comprehensive modular co-expression analyses.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {56}, pmid = {29458351}, issn = {1471-2105}, support = {2012/19278-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2013/08216-2//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 443719/2014-4//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; 305985/2014-0//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; }, mesh = {Automation ; Databases, Genetic ; Dengue/genetics ; Gene Expression Profiling ; *Gene Expression Regulation ; *Gene Regulatory Networks ; Humans ; Leishmaniasis, Visceral/genetics ; Psoriasis/genetics ; Sequence Analysis, RNA ; *Software ; Transcriptome/genetics ; }, abstract = {BACKGROUND: The analysis of modular gene co-expression networks is a well-established method commonly used for discovering the systems-level functionality of genes. In addition, these studies provide a basis for the discovery of clinically relevant molecular pathways underlying different diseases and conditions.

RESULTS: In this paper, we present a fast and easy-to-use Bioconductor package named CEMiTool that unifies the discovery and the analysis of co-expression modules. Using the same real datasets, we demonstrate that CEMiTool outperforms existing tools, and provides unique results in a user-friendly html report with high quality graphs. Among its features, our tool evaluates whether modules contain genes that are over-represented by specific pathways or that are altered in a specific sample group, as well as it integrates transcriptomic data with interactome information, identifying the potential hubs on each network. We successfully applied CEMiTool to over 1000 transcriptome datasets, and to a new RNA-seq dataset of patients infected with Leishmania, revealing novel insights of the disease's physiopathology.

CONCLUSION: The CEMiTool R package provides users with an easy-to-use method to automatically implement gene co-expression network analyses, obtain key information about the discovered gene modules using additional downstream analyses and retrieve publication-ready results via a high-quality interactive report.}, } @article {pmid29458340, year = {2018}, author = {Lappan, R and Imbrogno, K and Sikazwe, C and Anderson, D and Mok, D and Coates, H and Vijayasekaran, S and Bumbak, P and Blyth, CC and Jamieson, SE and Peacock, CS}, title = {A microbiome case-control study of recurrent acute otitis media identified potentially protective bacterial genera.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {13}, pmid = {29458340}, issn = {1471-2180}, abstract = {BACKGROUND: Recurrent acute otitis media (rAOM, recurrent ear infection) is a common childhood disease caused by bacteria termed otopathogens, for which current treatments have limited effectiveness. Generic probiotic therapies have shown promise, but seem to lack specificity. We hypothesised that healthy children with no history of AOM carry protective commensal bacteria that could be translated into a specific probiotic therapy to break the cycle of re-infection. We characterised the nasopharyngeal microbiome of these children (controls) in comparison to children with rAOM (cases) to identify potentially protective bacteria. As some children with rAOM do not appear to carry any of the known otopathogens, we also hypothesised that characterisation of the middle ear microbiome could identify novel otopathogens, which may also guide the development of more effective therapies.

RESULTS: Middle ear fluids, middle ear rinses and ear canal swabs from the cases and nasopharyngeal swabs from both groups underwent 16S rRNA gene sequencing. The nasopharyngeal microbiomes of cases and controls were distinct. We observed a significantly higher abundance of Corynebacterium and Dolosigranulum in the nasopharynx of controls. Alloiococcus, Staphylococcus and Turicella were abundant in the middle ear and ear canal of cases, but were uncommon in the nasopharynx of both groups. Gemella and Neisseria were characteristic of the case nasopharynx, but were not prevalent in the middle ear.

CONCLUSIONS: Corynebacterium and Dolosigranulum are characteristic of a healthy nasopharyngeal microbiome. Alloiococcus, Staphylococcus and Turicella are possible novel otopathogens, though their rarity in the nasopharynx and prevalence in the ear canal means that their role as normal aural flora cannot be ruled out. Gemella and Neisseria are unlikely to be novel otopathogens as they do not appear to colonise the middle ear in children with rAOM.}, } @article {pmid29458339, year = {2018}, author = {Guo, J and Shi, W and Zhang, Z and Cheng, J and Sun, D and Yu, J and Li, X and Guo, P and Hao, C}, title = {Association of yield-related traits in founder genotypes and derivatives of common wheat (Triticum aestivum L.).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {38}, pmid = {29458339}, issn = {1471-2229}, support = {2017YFD0101000//National Key R&D Program of China/ ; 2017142//Technology Innovation Program of Higher Education of Shanxi province/ ; 2016YJ05//Science & Technology Innovation Foundation of Shanxi Agricultural University/ ; }, mesh = {Alleles ; Chromosomes, Plant/genetics ; Genome-Wide Association Study ; *Genotype ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Quantitative Trait Loci/genetics ; Triticum/*genetics ; }, abstract = {BACKGROUND: Yield improvement is an ever-important objective of wheat breeding. Studying and understanding the phenotypes and genotypes of yield-related traits has potential for genetic improvement of crops.

RESULTS: The genotypes of 215 wheat cultivars including 11 founder parents and 106 derivatives were analyzed by the 9 K wheat SNP iSelect assay. A total of 4138 polymorphic single nucleotide polymorphism (SNP) loci were detected on 21 chromosomes, of which 3792 were mapped to single chromosome locations. All genotypes were phenotyped for six yield-related traits including plant height (PH), spike length (SL), spikelet number per spike (SNPS), kernel number per spike (KNPS), kernel weight per spike (KWPS), and thousand kernel weight (TKW) in six irrigated environments. Genome-wide association analysis detected 117 significant associations of 76 SNPs on 15 chromosomes with phenotypic explanation rates (R 2) ranging from 2.03 to 12.76%. In comparing allelic variation between founder parents and their derivatives (106) and other cultivars (98) using the 76 associated SNPs, we found that the region 116.0-133.2 cM on chromosome 5A in founder parents and derivatives carried alleles positively influencing kernel weight per spike (KWPS), rarely found in other cultivars.

CONCLUSION: The identified favorable alleles could mark important chromosome regions in derivatives that were inherited from founder parents. Our results unravel the genetic of yield in founder genotypes, and provide tools for marker-assisted selection for yield improvement.}, } @article {pmid29458331, year = {2018}, author = {Wang, Y and Pang, C and Li, X and Hu, Z and Lv, Z and Zheng, B and Chen, P}, title = {Correction to: Identification of tRNA nucleoside modification genes critical for stress response and development in rice and Arabidopsis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {37}, pmid = {29458331}, issn = {1471-2229}, abstract = {CORRECTION: Following publication of the original article [1], the authors reported that there was a mistake in the presentation of their funding information. The sentence "This study was supported by the National Natural Science Foundation of China (31,100,268 to Peng Chen, 31,270,658 to Bo Zheng);" should instead read "This study was supported by the National Natural Science Foundation of China (31100268 to Peng Chen, 31370604 to Bo Zheng);".}, } @article {pmid29458329, year = {2018}, author = {Ostromyshenskii, DI and Chernyaeva, EN and Kuznetsova, IS and Podgornaya, OI}, title = {Mouse chromocenters DNA content: sequencing and in silico analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {151}, pmid = {29458329}, issn = {1471-2164}, support = {11-04-01700//Russian Foundation for Basic Research/International ; 15-15-20026//Russian Science Foundation/International ; 01.2.01457147//Russian Academy of Sciences/International ; }, mesh = {Animals ; Chromosome Mapping ; *Chromosomes, Mammalian ; Computational Biology/methods ; Databases, Nucleic Acid ; Endogenous Retroviruses/genetics ; Heterochromatin/*genetics/metabolism ; High-Throughput Nucleotide Sequencing ; In Situ Hybridization, Fluorescence ; Long Interspersed Nucleotide Elements ; Mice ; Molecular Sequence Annotation ; Repetitive Sequences, Nucleic Acid ; Tandem Repeat Sequences ; }, abstract = {BACKGROUND: Chromocenters are defined as a punctate condensed blocks of chromatin in the interphase cell nuclei of certain cell types with unknown biological significance. In recent years a progress in revealing of chromocenters protein content has been made although the details of DNA content within constitutive heterochromatin still remain unclear. It is known that these regions are enriched in tandem repeats (TR) and transposable elements. Quick improvement of genome sequencing does not help to assemble the heterochromatic regions due to lack of appropriate bioinformatics techniques.

RESULTS: Chromocenters DNA have been isolated by a biochemical approach from mouse liver cells nuclei and sequenced on the Illumina MiSeq resulting in ChrmC dataset. Analysis of ChrmC dataset by the bioinformatics tools available revealed that the major component of chromocenter DNA are TRs: ~ 66% MaSat and ~ 4% MiSat. Other previously classified TR families constitute ~ 1% of ChrmC dataset. About 6% of chromocenters DNA are mostly unannotated sequences. In the contigs assembled with IDBA_UD there are many fragments of heterochromatic Y-chromosome, rDNA and other pseudo-genes and non-coding DNA. A protein coding sfi1 homolog gene fragment was also found in contigs. The Sfi1 homolog gene is located on the chromosome 11 in the reference genome very close to the Golden Pass Gap (a ~ 3 Mb empty region reserved to the pericentromeric region) and proves the purity of chromocenters isolation. The second major fraction are non-LTR retroposons (SINE and LINE) with overwhelming majority of LINE - ~ 11% of ChrmC. Most of the LINE fragments are from the ~ 2 kb region at the end of the 2nd ORF and its' flanking region. The precise LINEs' segment of ~ 2 kb is the necessary mouse constitutive heterohromatin component together with TR. The third most abundant fraction are ERVs. The ERV distribution in chromocenters differs from the whole genome: IAP (ERV2 class) is the most numerous in ChrmC while MaLR (ERV3 class) prevails in the reference genome. IAP and its LTR also prevail in TR containing contigs extracted from the WGS dataset. In silico prediction of IAP and LINE fragments in chromocenters was confirmed by direct fluorescent in situ hybridization (FISH).

CONCLUSION: Our data of chromocenters' DNA (ChrmC) sequencing demonstrate that IAP with LTR and a precise ~ 2 kb fragment of LINE represent a substantial fraction of mouse chromocenters (constitutive heteroсhromatin) along with TRs.}, } @article {pmid29458328, year = {2018}, author = {Mantsoki, A and Devailly, G and Joshi, A}, title = {Dynamics of promoter bivalency and RNAP II pausing in mouse stem and differentiated cells.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {2}, pmid = {29458328}, issn = {1471-213X}, support = {BBSRC, BB/J004235/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; PCOFUND-GA-2012-600181//H2020 Marie Skłodowska-Curie Actions/International ; }, abstract = {BACKGROUND: Mammalian embryonic stem cells display a unique epigenetic and transcriptional state to facilitate pluripotency by maintaining lineage-specification genes in a poised state. Two epigenetic and transcription processes involved in maintaining poised state are bivalent chromatin, characterized by the simultaneous presence of activating and repressive histone methylation marks, and RNA polymerase II (RNAPII) promoter proximal pausing. However, the dynamics of histone modifications and RNAPII at promoters in diverse cellular contexts remains underexplored.

RESULTS: We collected genome wide data for bivalent chromatin marks H3K4me3 and H3K27me3, and RNAPII (8WG16) occupancy together with expression profiling in eight different cell types, including ESCs, in mouse. The epigenetic and transcription profiles at promoters grouped in over thirty clusters with distinct functional identities and transcription control.

CONCLUSION: The clustering analysis identified distinct bivalent clusters where genes in one cluster retained bivalency across cell types while in the other were mostly cell type specific, but neither showed a high RNAPII pausing. We noted that RNAPII pausing is more associated with active genes than bivalent genes in a cell type, and was globally reduced in differentiated cell types compared to multipotent.}, } @article {pmid29458327, year = {2018}, author = {Xi, Y and Shi, J and Li, W and Tanaka, K and Allton, KL and Richardson, D and Li, J and Franco, HL and Nagari, A and Malladi, VS and Coletta, LD and Simper, MS and Keyomarsi, K and Shen, J and Bedford, MT and Shi, X and Barton, MC and Kraus, WL and Li, W and Dent, SYR}, title = {Histone modification profiling in breast cancer cell lines highlights commonalities and differences among subtypes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {150}, pmid = {29458327}, issn = {1471-2164}, support = {RP100417//Cancer Prevention and Research Institute of Texas/International ; RP120348//Cancer Prevention and Research Institute of Texas/International ; }, mesh = {Biomarkers, Tumor ; Breast Neoplasms/*genetics/*metabolism/pathology ; Cell Line, Tumor ; Chromatin/genetics/metabolism ; *Epigenesis, Genetic ; Female ; Gene Expression Profiling ; *Gene Expression Regulation, Neoplastic ; Histones/*metabolism ; Humans ; Transcriptome ; }, abstract = {BACKGROUND: Epigenetic regulators are frequently mutated or aberrantly expressed in a variety of cancers, leading to altered transcription states that result in changes in cell identity, behavior, and response to therapy.

RESULTS: To define alterations in epigenetic landscapes in breast cancers, we profiled the distributions of 8 key histone modifications by ChIP-Seq, as well as primary (GRO-seq) and steady state (RNA-Seq) transcriptomes, across 13 distinct cell lines that represent 5 molecular subtypes of breast cancer and immortalized human mammary epithelial cells.

DISCUSSION: Using combinatorial patterns of distinct histone modification signals, we defined subtype-specific chromatin signatures to nominate potential biomarkers. This approach identified AFAP1-AS1 as a triple negative breast cancer-specific gene associated with cell proliferation and epithelial-mesenchymal-transition. In addition, our chromatin mapping data in basal TNBC cell lines are consistent with gene expression patterns in TCGA that indicate decreased activity of the androgen receptor pathway but increased activity of the vitamin D biosynthesis pathway.

CONCLUSIONS: Together, these datasets provide a comprehensive resource for histone modification profiles that define epigenetic landscapes and reveal key chromatin signatures in breast cancer cell line subtypes with potential to identify novel and actionable targets for treatment.}, } @article {pmid29458326, year = {2018}, author = {Suzuki, G and Wang, Y and Kubo, K and Hirata, E and Ohnuki, S and Ohya, Y}, title = {Global study of holistic morphological effectors in the budding yeast Saccharomyces cerevisiae.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {149}, pmid = {29458326}, issn = {1471-2164}, support = {24370002//Ministry of Education, Culture, Sports, Science and Technology (JP)/International ; }, mesh = {Autophagy/genetics ; Gene Deletion ; Gene Duplication ; Gene Expression Regulation, Fungal ; *Genetic Association Studies/methods ; Genetic Fitness ; Genome, Fungal ; Mutation ; *Phenotype ; *Quantitative Trait, Heritable ; Reproducibility of Results ; Saccharomyces cerevisiae/*cytology/*physiology ; Saccharomyces cerevisiae Proteins/genetics ; }, abstract = {BACKGROUND: The size of the phenotypic effect of a gene has been thoroughly investigated in terms of fitness and specific morphological traits in the budding yeast Saccharomyces cerevisiae, but little is known about gross morphological abnormalities.

RESULTS: We identified 1126 holistic morphological effectors that cause severe gross morphological abnormality when deleted, and 2241 specific morphological effectors with weak holistic effects but distinctive effects on yeast morphology. Holistic effectors fell into many gene function categories and acted as network hubs, affecting a large number of morphological traits, interacting with a large number of genes, and facilitating high protein expression. Holistic morphological abnormality was useful for estimating the importance of a gene to morphology. The contribution of gene importance to fitness and morphology could be used to efficiently classify genes into functional groups.

CONCLUSION: Holistic morphological abnormality can be used as a reproducible and reliable gene feature for high-dimensional morphological phenotyping. It can be used in many functional genomic applications.}, } @article {pmid29457705, year = {2018}, author = {Hoskisson, PA and Fernández-Martínez, LT}, title = {Regulation of specialised metabolites in Actinobacteria - expanding the paradigms.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {231-238}, pmid = {29457705}, issn = {1758-2229}, support = {BB/N023544/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The increase in availability of actinobacterial whole genome sequences has revealed huge numbers of specialised metabolite biosynthetic gene clusters, encoding a range of bioactive molecules such as antibiotics, antifungals, immunosuppressives and anticancer agents. Yet the majority of these clusters are not expressed under standard laboratory conditions in rich media. Emerging data from studies of specialised metabolite biosynthesis suggest that the diversity of regulatory mechanisms is greater than previously thought and these act at multiple levels, through a range of signals such as nutrient limitation, intercellular signalling and competition with other organisms. Understanding the regulation and environmental cues that lead to the production of these compounds allows us to identify the role that these compounds play in their natural habitat as well as provide tools to exploit this untapped source of specialised metabolites for therapeutic uses. Here, we provide an overview of novel regulatory mechanisms that act in physiological, global and cluster-specific regulatory manners on biosynthetic pathways in Actinobacteria and consider these alongside their ecological and evolutionary implications.}, } @article {pmid29457693, year = {2018}, author = {Conthe, M and Wittorf, L and Kuenen, JG and Kleerebezem, R and Hallin, S and van Loosdrecht, MCM}, title = {Growth yield and selection of nosZ clade II types in a continuous enrichment culture of N2 O respiring bacteria.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {239-244}, doi = {10.1111/1758-2229.12630}, pmid = {29457693}, issn = {1758-2229}, abstract = {Nitrous oxide (N2 O) reducing microorganisms may be key in the mitigation of N2 O emissions from managed ecosystems. However, there is still no clear understanding of the physiological and bioenergetic implications of microorganisms possessing either of the two N2 O reductase genes (nosZ), clade I and the more recently described clade II type nosZ. It has been suggested that organisms with nosZ clade II have higher growth yields and a lower affinity constant (Ks) for N2 O. We compared N2 O reducing communities with different nosZI/nosZII ratios selected in chemostat enrichment cultures, inoculated with activated sludge, fed with N2 O as a sole electron acceptor and growth limiting factor and acetate as electron donor. From the sequencing of the 16S rRNA gene, FISH and quantitative PCR of nosZ and nir genes, we concluded that betaproteobacterial denitrifying organisms dominated the enrichments with members within the family Rhodocyclaceae being highly abundant. When comparing cultures with different nosZI/nosZII ratios, we did not find support for (i) a more energy conserving N2 O respiration pathway in nosZ clade II systems, as reflected in the growth yield per mole of substrate, or (ii) a higher affinity for N2 O, defined by μmax /Ks , in organisms with nosZ clade II.}, } @article {pmid29457691, year = {2018}, author = {Gougoulias, C and Meade, A and Shaw, LJ}, title = {Apportioning bacterial carbon source utilization in soil using 14 C isotope analysis of FISH-targeted bacterial populations sorted by fluorescence activated cell sorting (FACS): 14 C-FISH-FACS.}, journal = {Environmental microbiology reports}, volume = {10}, number = {3}, pages = {245-254}, doi = {10.1111/1758-2229.12631}, pmid = {29457691}, issn = {1758-2229}, support = {BB/F000251/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {An unresolved need in microbial ecology is methodology to enable quantitative analysis of in situ microbial substrate carbon use at the population level. Here, we evaluated if a novel combination of radiocarbon-labelled substrate tracing, fluorescence in situ hybridisation (FISH) and fluorescence-activated cell sorting (FACS) to sort the FISH-targeted population for quantification of incorporated radioactivity (14 C-FISH-FACS) can address this need. Our test scenario used FISH probe PSE1284 targeting Pseudomonas spp. (and some Burkholderia spp.) and salicylic acid added to rhizosphere soil. We examined salicylic acid-14 C fate (mineralized, cell-incorporated, extractable and non-extractable) and mass balance (0-24 h) and show that the PSE1284 population captured ∼ 50% of the Nycodenz extracted biomass 14 C. Analysis of the taxonomic distribution of the salicylic acid biodegradation trait suggested that PSE1284 population success was not due to conservation of this trait but due to competitiveness for the added carbon. Adding 50KBq of 14 C sample-1 enabled detection of 14 C in the sorted population at ∼ 60-600 times background; a sensitivity which demonstrates potential extension to analysis of rarer/less active populations. Given its sensitivity and compatibility with obtaining a C mass balance, 14 C-FISH-FACS allows quantitative dissection of C flow within the microbial biomass that has hitherto not been achieved.}, } @article {pmid29457688, year = {2018}, author = {Chen, AI and Goulian, M}, title = {A network of regulators promotes dehydration tolerance in Escherichia coli.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1283-1295}, pmid = {29457688}, issn = {1462-2920}, support = {R01 GM080279/GM/NIGMS NIH HHS/United States ; }, abstract = {The ability to survive conditions of low water activity is critical for the survival of many bacteria in the environment and facilitates disease transmission through food and contaminated surfaces. However, the molecular mechanisms that enable bacteria to withstand this condition remain poorly understood. Here we describe a network of regulators in Escherichia coli that are important for this bacterium to survive dehydration. We found that the transcriptional regulator DksA and the general stress response regulator RpoS play a critical role. From a plasmid genomic library screen, we identified two additional regulators, Crl and ArcZ, that promote dehydration tolerance through modulation of RpoS. We also found that LexA, RecA and ArcA contribute to survival. Our results identify key regulators that enable E. coli to tolerate dehydration and suggest a hierarchical network is involved in protection against cellular damage associated with this stress.}, } @article {pmid29457686, year = {2018}, author = {Kim, JS and Chowdhury, N and Yamasaki, R and Wood, TK}, title = {Viable but non-culturable and persistence describe the same bacterial stress state.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14075}, pmid = {29457686}, issn = {1462-2920}, abstract = {Bacteria are often thought of as having two dormant phenotypes: the viable but non-culturable (VBNC) state and the persister state. Here we investigate the relatedness of the two stress-induced phenotypes at the single-cell level and examine cell morphology and quantify cell resuscitation. Using the classic starvation conditions to create VBNC cells, we found that the majority of the remaining Escherichia coli population are spherical, have empty cytosol and fail to resuscitate; however, some of the spherical cells resuscitate immediately (most probably those with dense cytosol). Critically, all the culturable cells in this starved population became persister cells within 14 days of starvation. We found that the persister cells initially are rod-like, have clear but limited membrane damage, can resuscitate immediately and gradually become spherical by aging. After 24 h, only rod-shaped persister cells survive, and all the spherical cells lyse. Both cell populations formed under the VBNC-inducing conditions and the persister conditions are metabolically inactive. Therefore, the bacterial population consists of dead cells and persister cells in the VBNC-inducing conditions; that is, the non-lysed particles that do not resuscitate are dead, and the dormant cells that resuscitate are persister cells. Hence, 'VBNC' and 'persister' describe the same dormant phenotype.}, } @article {pmid29457222, year = {2018}, author = {Hundt, PJ and Simons, AM}, title = {Extreme dentition does not prevent diet and tooth diversification within combtooth blennies (Ovalentaria: Blenniidae).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {930-943}, doi = {10.1111/evo.13453}, pmid = {29457222}, issn = {1558-5646}, abstract = {The dentition of fishes can be quite striking and is often correlated with a specific diet. Combtooth blennies have long incisiform oral teeth, unlike most actinopterygians. It has been suggested that the long tooth morphology is an adaptation for detritivory, but given the diversity of diets (detritus, coral polyps, polychaetes, and pieces of other fishes), are blenny teeth indeed monomorphic? Or does tooth variation associated with diet still exist at this extreme? To explore tooth and diet diversification, we used a new phylogenetic hypothesis of Blenniidae, measured tooth shape, number, and mode of attachment, and quantified blenniid diet. The ancestral diet of blennies contained detritus and diversified into many different diets, including almost exclusively detritivory. Our results reveal a dental cline that may be constrained by tooth shape, but has not prevented diet diversification. Ancestral state reconstruction of tooth morphologies suggests that the ancestor of blennies had many unattached teeth and featured transitions to fewer attached teeth, with several transitions back to attached or unattached teeth. The dentition of blenniids is not monotypic; rather it is diverse and small changes in tooth shape are accompanied by changes in size, number, attachment, and often diet.}, } @article {pmid29456829, year = {2018}, author = {Cox, SL and Orgeret, F and Gesta, M and Rodde, C and Heizer, I and Weimerskirch, H and Guinet, C}, title = {Processing of acceleration and dive data on-board satellite relay tags to investigate diving and foraging behaviour in free-ranging marine predators.}, journal = {Methods in ecology and evolution}, volume = {9}, number = {1}, pages = {64-77}, pmid = {29456829}, issn = {2041-210X}, abstract = {Biologging technologies are changing the way in which the marine environment is observed and monitored. However, because device retrieval is typically required to access the high-resolution data they collect, their use is generally restricted to those animals that predictably return to land. Data abstraction and transmission techniques aim to address this, although currently these are limited in scope and do not incorporate, for example, acceleration measurements which can quantify animal behaviours and movement patterns over fine-scales.In this study, we present a new method for the collection, abstraction and transmission of accelerometer data from free-ranging marine predators via the Argos satellite system. We test run the technique on 20 juvenile southern elephant seals Mirounga leonina from the Kerguelen Islands during their first months at sea following weaning. Using retrieved archival data from nine individuals that returned to the colony, we compare and validate abstracted transmissions against outputs from established accelerometer processing procedures.Abstracted transmissions included estimates, across five segments of a dive profile, of time spent in prey catch attempt (PrCA) behaviours, swimming effort and pitch. These were then summarised and compared to archival outputs across three dive phases: descent, bottom and ascent. Correlations between the two datasets were variable but generally good (dependent on dive phase, marginal R2 values of between .45 and .6 to >.9) and consistent between individuals. Transmitted estimates of PrCA behaviours and swimming effort were positively biased to those from archival processing.Data from this study represent some of the first remotely transmitted quantifications from accelerometers. The methods presented and analysed can be used to provide novel insight towards the behaviours and movements of free-ranging marine predators, such as juvenile southern elephant seals, from whom logger retrieval is challenging. Future applications could however benefit from some adaption, particularly to reduce positive bias in transmitted PrCA behaviours and swimming effort, for which this study provides useful insight.}, } @article {pmid29456250, year = {2018}, author = {Wright, CF and FitzPatrick, DR and Firth, HV}, title = {Paediatric genomics: diagnosing rare disease in children.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {325}, doi = {10.1038/nrg.2018.12}, pmid = {29456250}, issn = {1471-0064}, support = {MC_PC_U127561093//Medical Research Council/United Kingdom ; }, abstract = {This corrects the article DOI: 10.1038/nrg.2017.116.}, } @article {pmid29456249, year = {2018}, author = {Trenkmann, M}, title = {RNA: Follow the SINE for nuclear localization.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {188-189}, pmid = {29456249}, issn = {1471-0064}, } @article {pmid29456248, year = {2018}, author = {Perdigoto, C}, title = {Genetic variation: Putting causal variants on the map.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {188-189}, pmid = {29456248}, issn = {1471-0064}, } @article {pmid29456244, year = {2018}, author = {Pike, LJ and Forster, SC}, title = {A new piece in the microbiome puzzle.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {186}, pmid = {29456244}, issn = {1740-1534}, } @article {pmid29456243, year = {2018}, author = {Belin, BJ and Busset, N and Giraud, E and Molinaro, A and Silipo, A and Newman, DK}, title = {Hopanoid lipids: from membranes to plant-bacteria interactions.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {304-315}, pmid = {29456243}, issn = {1740-1534}, support = {K99 GM126141/GM/NIGMS NIH HHS/United States ; }, abstract = {Lipid research represents a frontier for microbiology, as showcased by hopanoid lipids. Hopanoids, which resemble sterols and are found in the membranes of diverse bacteria, have left an extensive molecular fossil record. They were first discovered by petroleum geologists. Today, hopanoid-producing bacteria remain abundant in various ecosystems, such as the rhizosphere. Recently, great progress has been made in our understanding of hopanoid biosynthesis, facilitated in part by technical advances in lipid identification and quantification. A variety of genetically tractable, hopanoid-producing bacteria have been cultured, and tools to manipulate hopanoid biosynthesis and detect hopanoids are improving. However, we still have much to learn regarding how hopanoid production is regulated, how hopanoids act biophysically and biochemically, and how their production affects bacterial interactions with other organisms, such as plants. The study of hopanoids thus offers rich opportunities for discovery.}, } @article {pmid29456242, year = {2018}, author = {Du Toit, A}, title = {Bacterial pathogenesis: Channelling the host epigenome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {184-185}, pmid = {29456242}, issn = {1740-1534}, } @article {pmid29456241, year = {2018}, author = {Gagneux, S}, title = {Ecology and evolution of Mycobacterium tuberculosis.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {202-213}, pmid = {29456241}, issn = {1740-1534}, abstract = {Tuberculosis (TB) is the number one cause of human death due to an infectious disease. The causative agents of TB are a group of closely related bacteria known as the Mycobacterium tuberculosis complex (MTBC). As the MTBC exhibits a clonal population structure with low DNA sequence diversity, methods (such as multilocus sequence typing) that are applied to more genetically diverse bacteria are uninformative, and much of the ecology and evolution of the MTBC has therefore remained unknown. Owing to recent advances in whole-genome sequencing and analyses of large collections of MTBC clinical isolates from around the world, many new insights have been gained, including a better understanding of the origin of the MTBC as an obligate pathogen and its molecular evolution and population genetic characteristics both within and between hosts, as well as many aspects related to antibiotic resistance. The purpose of this Review is to summarize these recent discoveries and discuss their relevance for developing better tools and strategies to control TB.}, } @article {pmid29456201, year = {2018}, author = {Merchant, RR and Edwards, JT and Qin, T and Kruszyk, MM and Bi, C and Che, G and Bao, DH and Qiao, W and Sun, L and Collins, MR and Fadeyi, OO and Gallego, GM and Mousseau, JJ and Nuhant, P and Baran, PS}, title = {Modular radical cross-coupling with sulfones enables access to sp3-rich (fluoro)alkylated scaffolds.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6384}, pages = {75-80}, doi = {10.1126/science.aar7335}, pmid = {29456201}, issn = {1095-9203}, support = {R35 GM118176/GM/NIGMS NIH HHS/United States ; }, abstract = {Cross-coupling chemistry is widely applied to carbon-carbon bond formation in the synthesis of medicines, agrochemicals, and other functional materials. Recently, single-electron-induced variants of this reaction class have proven particularly useful in the formation of C(sp2)-C(sp3) linkages, although certain compound classes have remained a challenge. Here, we report the use of sulfones to activate the alkyl coupling partner in nickel-catalyzed radical cross-coupling with aryl zinc reagents. This method's tolerance of fluoroalkyl substituents proved particularly advantageous for the streamlined preparation of pharmaceutically oriented fluorinated scaffolds that previously required multiple steps, toxic reagents, and nonmodular retrosynthetic blueprints. Five specific sulfone reagents facilitate the rapid assembly of a vast set of compounds, many of which contain challenging fluorination patterns.}, } @article {pmid29456188, year = {2018}, author = {Frainer, A and McKie, BG and Amundsen, PA and Knudsen, R and Lafferty, KD}, title = {Parasitism and the Biodiversity-Functioning Relationship.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {260-268}, doi = {10.1016/j.tree.2018.01.011}, pmid = {29456188}, issn = {1872-8383}, mesh = {*Biodiversity ; Ecosystem ; *Host-Parasite Interactions ; *Models, Biological ; }, abstract = {Species interactions can influence ecosystem functioning by enhancing or suppressing the activities of species that drive ecosystem processes, or by causing changes in biodiversity. However, one important class of species interactions - parasitism - has been little considered in biodiversity and ecosystem functioning (BD-EF) research. Parasites might increase or decrease ecosystem processes by reducing host abundance. Parasites could also increase trait diversity by suppressing dominant species or by increasing within-host trait diversity. These different mechanisms by which parasites might affect ecosystem function pose challenges in predicting their net effects. Nonetheless, given the ubiquity of parasites, we propose that parasite-host interactions should be incorporated into the BD-EF framework.}, } @article {pmid29455569, year = {2018}, author = {Shabbir, M and Zon, AMY and Thuppil, V}, title = {Repetition Is the Feature Behind the Attentional Bias for Recognizing Threatening Patterns.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704918754782}, doi = {10.1177/1474704918754782}, pmid = {29455569}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Attention/physiology ; Attentional Bias/*physiology ; Female ; Humans ; Male ; Pattern Recognition, Visual/*physiology ; Photic Stimulation ; Reaction Time/*physiology ; Young Adult ; }, abstract = {Animals attend to what is relevant in order to behave in an effective manner and succeed in their environments. In several nonhuman species, there is an evolved bias for attending to patterns indicative of threats in the natural environment such as dangerous animals. Because skins of many dangerous animals are typically repetitive, we propose that repetition is the key feature enabling recognition of evolutionarily important threats. The current study consists of two experiments where we measured participants' reactions to pictures of male and female models wearing clothing of various repeating (leopard skin, snakeskin, and floral print) and nonrepeating (camouflage, shiny, and plain) patterns. In Experiment 1, when models wearing patterns were presented side by side with total fixation duration as the measure, the repeating floral pattern was the most provocative, with total fixation duration significantly longer than all other patterns. Leopard and snakeskin patterns had total fixation durations that were significantly longer than the plain pattern. In Experiment 2, we employed a visual-search task where participants were required to find models wearing the various patterns in a setting of a crowded airport terminal. Participants detected leopard skin pattern and repetitive floral pattern significantly faster than two of the nonpatterned clothing styles. Our experimental findings support the hypothesis that repetition of specific visual features might facilitate target detection, especially those characterizing evolutionary important threats. Our findings that intricate, but nonthreatening repeating patterns can have similar attention-grabbing properties to animal skin patterns have important implications for the fashion industry and wildlife trade.}, } @article {pmid29455469, year = {2018}, author = {Agrawal, AA and Hastings, AP and Fines, DM and Bogdanowicz, S and Huber, M}, title = {Insect herbivory and plant adaptation in an early successional community.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1020-1033}, doi = {10.1111/evo.13451}, pmid = {29455469}, issn = {1558-5646}, abstract = {To address the role of insect herbivores in adaptation of plant populations and the persistence of selection through succession, we manipulated herbivory in a long-term field experiment. We suppressed insects in half of 16 plots over nine years and examined the genotypic structure and chemical defense of common dandelion (Taraxacum officinale), a naturally colonizing perennial apomictic plant. Insect suppression doubled dandelion abundance in the first few years, but had negligible effects thereafter. Using microsatellite DNA markers, we genotyped >2500 plants and demonstrate that insect suppression altered the genotypic composition of plots in both sampling years. Phenotypic and genotypic estimates of defensive terpenes and phenolics from the field plots allowed us to infer phenotypic plasticity and the response of dandelion populations to insect-mediated natural selection. The effects of insect suppression on plant chemistry were, indeed, driven both by plasticity and plant genotypic identity. In particular, di-phenolic inositol esters were more abundant in plots exposed to herbivory (due to the genotypic composition of the plots) and were also induced in response to herbivory. This field experiment thus demonstrates evolutionary sorting of plant genotypes in response to insect herbivores that was in same direction as the plastic defensive response within genotypes.}, } @article {pmid29455461, year = {2018}, author = {McCullough, EL and Buzatto, BA and Simmons, LW}, title = {Population density mediates the interaction between pre- and postmating sexual selection.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {893-905}, doi = {10.1111/evo.13455}, pmid = {29455461}, issn = {1558-5646}, abstract = {When females mate with more than one male, sexual selection acts both before and after mating. The interaction between pre- and postmating episodes of selection is expected to be context dependent, but few studies have investigated how total sexual selection changes under different ecological conditions. We examined how population density mediates the interaction between pre- and postmating sexual selection by establishing replicate populations of the horned dung beetle Onthophagus taurus at low, medium, and high densities, and then using microsatellite-based parentage analyses to measure male fitness. We found that mating success and fertilization success were positively correlated at all three densities, but the strength of the correlation decreased with increasing density. We also found a shift from negative to positive linear selection on testes mass as density increased, and opposing selection on weapons and testes at high densities. These patterns suggest that the importance of postmating processes increases with increasing population density, which reduces the selective advantage of weapons for premating contest competition, and increases the selective advantage of large ejaculates for postmating sperm competition. We expect that density-dependent selection on testes mass has contributed to the phenotypic variation observed between natural populations of O. taurus that differ in density.}, } @article {pmid29455279, year = {2018}, author = {Tian, R and Chen, M and Chai, S and Rong, X and Chen, B and Ren, W and Xu, S and Yang, G}, title = {Divergent Selection of Pattern Recognition Receptors in Mammals with Different Ecological Characteristics.}, journal = {Journal of molecular evolution}, volume = {86}, number = {2}, pages = {138-149}, doi = {10.1007/s00239-018-9832-1}, pmid = {29455279}, issn = {1432-1432}, support = {2016YFC0503200//National Key Programme of Research and Development, Ministry of Science and Technology/ ; 31630071//National Natural Science Foundation of China (NSFC)/ ; 31570379//National Natural Science Foundation of China (NSFC)/ ; BK20141449//Natural Science Foundation of Jiangsu Province of China/ ; 31325025//the National Science Fund for Distinguished Young Scholars/ ; 31772448//National Natural Science Foundation of China (CN)/ ; }, abstract = {Pattern recognition receptors (PRRs) are specialized receptors that represent a key component of the host innate immune system. Whether molecular evolutionary history of different PRR classes have involved different genetic mechanisms underlying diverse pathogen environment in mammals, and whether distinct ecology of mammals may have imposed divergent selective pressures on the evolution of the PRRs, remained unknown. To test these hypotheses, we investigated the characterization of 20 genes belonging to four PRR classes in mammals. Evidence of positive selection was found in most (17 of 20) PRR genes examined, and most positively selected sites (84%) undergoing radical changes were found to fall in important functional regions, consistent with the co-evolutionary dynamics between the hosts and their microbial counterparts. We found different evolutionary patterns in different PRR classes, with the highest level of positive selection in C-type lectin receptor (CLR) family, suggesting that the capability of CLRs in response to a wide variety of ligands might explain their malleability to selection pressures. Tests using branch models that partitioned the data along habitat and social behavior found significant evidence of divergent selective pressures of PRRs among mammalian groups. Interestingly, species-specific evolution was detected on RIG-I-like helicase genes (RLRs) in cetaceans, suggesting that RLRs might play a critical role in the defense against widespread marine RNA viruses during their divergence and radiation into marine habitats. This study provides a comprehensive look at the evolutionary patterns and implications of mammalian PRRs, and highlights the importance of ecological influences in molecular adaptation.}, } @article {pmid29455143, year = {2018}, author = {Fouché, S and Plissonneau, C and Croll, D}, title = {The birth and death of effectors in rapidly evolving filamentous pathogen genomes.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {34-42}, doi = {10.1016/j.mib.2018.01.020}, pmid = {29455143}, issn = {1879-0364}, abstract = {Plant pathogenic fungi and oomycetes are major risks to food security due to their evolutionary success in overcoming plant defences. Pathogens produce effectors to interfere with host defences and metabolism. These effectors are often encoded in rapidly evolving compartments of the genome. We review how effector genes emerged and were lost in pathogen genomes drawing on the links between effector evolution and chromosomal rearrangements. Some new effectors entered pathogen genomes via horizontal transfer or introgression. However, new effector functions also arose through gene duplication or from previously non-coding sequences. The evolutionary success of an effector is tightly linked to its transcriptional regulation during host colonization. Some effectors converged on an epigenetic control of expression imposed by genomic defences against transposable elements. Transposable elements were also drivers of effector diversification and loss that led to mosaics in effector presence-absence variation. Such effector mosaics within species was the foundation for rapid pathogen adaptation.}, } @article {pmid29455142, year = {2018}, author = {Bourras, S and Praz, CR and Spanu, PD and Keller, B}, title = {Cereal powdery mildew effectors: a complex toolbox for an obligate pathogen.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {26-33}, doi = {10.1016/j.mib.2018.01.018}, pmid = {29455142}, issn = {1879-0364}, support = {163260//Swiss National Science Foundation/Switzerland ; }, abstract = {Cereal powdery mildews are major pathogens of cultivated monocot crops, and all are obligate biotrophic fungi that can only grow and reproduce on living hosts. This lifestyle is combined with extreme host specialization where every mildew subspecies (referred to as forma specialis) can only infect one plant species. Recently there has been much progress in our understanding of the possible roles effectors play in this complex host-pathogen interaction. Here, we review current knowledge on the origin, evolution, and mode of action of cereal mildew effectors, with a particular focus on recent advances in the identification of bona fide effectors and avirulence effector proteins from wheat and barley powdery mildews.}, } @article {pmid29454931, year = {2018}, author = {Jansson, JK and Hofmockel, KS}, title = {The soil microbiome-from metagenomics to metaphenomics.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {162-168}, doi = {10.1016/j.mib.2018.01.013}, pmid = {29454931}, issn = {1879-0364}, mesh = {Bacteria/*genetics/metabolism ; Bacterial Physiological Phenomena/genetics ; Biodiversity ; Carbon/metabolism ; Metabolic Networks and Pathways ; Metagenomics ; Microbiota/*genetics/physiology ; *Phenotype ; Phylogeny ; *Soil Microbiology ; }, abstract = {Soil microorganisms carry out important processes, including support of plant growth and cycling of carbon and other nutrients. However, the majority of soil microbes have not yet been isolated and their functions are largely unknown. Although metagenomic sequencing reveals microbial identities and functional gene information, it includes DNA from microbes with vastly varying physiological states. Therefore, metagenomics is only predictive of community functional potential. We posit that the next frontier lies in understanding the metaphenome, the product of the combined genetic potential of the microbiome and available resources. Here we describe examples of opportunities towards gaining understanding of the soil metaphenome.}, } @article {pmid29454930, year = {2018}, author = {Elbaum, M}, title = {Expanding horizons of cryo-tomography to larger volumes.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {155-161}, doi = {10.1016/j.mib.2018.01.001}, pmid = {29454930}, issn = {1879-0364}, mesh = {Animals ; Cells/*ultrastructure ; Electron Microscope Tomography/instrumentation/*methods ; Humans ; Imaging, Three-Dimensional/instrumentation/methods ; Microscopy, Electron, Scanning/instrumentation/methods ; }, abstract = {The three dimensional ultrastructure of cells and tissues comes to light with tomography. There is an inherent tension between representing molecular detail at the highest possible resolution, on one hand, and visualizing spatial relations between large organelles or even neighboring cells in large volumes, on the other. Together with its advantages for pristine sample preservation, cryo-tomography brings particular constraints. A major challenge has been the restriction to specimens thinner than the typical cell. New imaging modalities are now available to extend cryo-tomography to thicker specimens: cryo-scanning transmission electron tomography (CSTET), soft X-ray tomography (SXT), and serial surface imaging using the focused ion beam-scanning electron microscope (FIB-SEM). Each one offers specific advantages so the optimal choice depends on priorities among resolution, composition, and volume.}, } @article {pmid29454889, year = {2018}, author = {Duan, T and Deng, X and Chen, S and Luo, Z and Zhao, Z and Tu, T and Khang, NS and Razafimandimbison, SG and Zhang, D}, title = {Evolution of sexual systems and growth habit in Mussaenda (Rubiaceae): Insights into the evolutionary pathways of dioecy.}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {113-122}, doi = {10.1016/j.ympev.2018.02.015}, pmid = {29454889}, issn = {1095-9513}, mesh = {Biodiversity ; *Biological Evolution ; Models, Theoretical ; Phylogeny ; Probability ; Rubiaceae/*classification/*growth & development ; Time Factors ; }, abstract = {Dioecy is a rare sexual system that is thought to represent an "evolutionary dead end". While many studies have addressed the evolution of dioecy and/or its relationship with the evolution of the woody habit, few have explored the relationship between dioecy and climbing habit, and their effects on diversification rates. Here, we study the evolution of sexual systems and growth habit in Mussaenda (Rubiaceae) using a robust phylogeny of the genus based on eight plastid regions and a broad sampling of taxa (92 of the 132 species were sampled). A time-calibrated tree was constructed to estimate diversification rates in different clades and its correlates with focal characters. More specifically, we assess evolutionary correlations between dioecy and climbing habit and their respective influences on diversification rates. Ancestral character state reconstructions revealed that distyly is the most likely ancestral state in Mussaenda. Distyly has subsequently given rise to dioecy, short-styled floral monomorphism, and long-styled floral monomorphism. Dioecy has evolved independently at least four times from distyly, and has reversed to homostylous hermaphroditism at least twice, which does not support the "evolutionary dead end" hypothesis. A significant correlation between the evolution of dioecy and climbing growth form was found in Mussaenda. It is possible that a strong association between high net diversification rates and dioecy may exist in Mussaenda, but no association was found with climbing habit.}, } @article {pmid29454787, year = {2018}, author = {Zgurskaya, HI and Rybenkov, VV and Krishnamoorthy, G and Leus, IV}, title = {Trans-envelope multidrug efflux pumps of Gram-negative bacteria and their synergism with the outer membrane barrier.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {351-356}, pmid = {29454787}, issn = {1769-7123}, support = {R01 AI052293/AI/NIAID NIH HHS/United States ; R01 AI132836/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*metabolism/pharmacology ; Bacterial Outer Membrane Proteins/genetics/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Biological Transport ; Gram-Negative Bacteria/drug effects/genetics/*metabolism ; Membrane Transport Proteins/genetics/*metabolism ; }, abstract = {Antibiotic resistance is a serious threat to public health. Significant efforts are currently directed toward containment of the spread of resistance, finding new therapeutic options concerning resistant human and animal pathogens, and addressing the gaps in the fundamental understanding of mechanisms of resistance. Experimental data and kinetic modeling revealed a major factor in resistance, the synergy between active efflux and the low permeability barrier of the outer membrane, which dramatically reduces the intracellular accumulation of many antibiotics. The structural and mechanistic particularities of trans-envelope efflux pumps amplify the effectiveness of cell envelopes as permeability barriers. An important feature of this synergism is that efflux pumps and the outer membrane barriers are mechanistically independent and select antibiotics based on different physicochemical properties. The synergism amplifies even weak polyspecificity of multidrug efflux pumps and creates a major hurdle in the discovery and development of new therapeutics against Gram-negative pathogens.}, } @article {pmid29454706, year = {2018}, author = {Meng, Y and Moore, R and Tao, W and Smith, ER and Tse, JD and Caslini, C and Xu, XX}, title = {GATA6 phosphorylation by Erk1/2 propels exit from pluripotency and commitment to primitive endoderm.}, journal = {Developmental biology}, volume = {436}, number = {1}, pages = {55-65}, pmid = {29454706}, issn = {1095-564X}, support = {R01 CA079716/CA/NCI NIH HHS/United States ; R01 CA095071/CA/NCI NIH HHS/United States ; R01 CA099471/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Blotting, Western ; Cell Differentiation/genetics ; Cell Line ; Embryonic Stem Cells/*metabolism ; Endoderm/embryology/*metabolism ; Fluorescent Antibody Technique ; GATA6 Transcription Factor/genetics/*metabolism ; Gene Expression Regulation, Developmental ; MAP Kinase Signaling System/*genetics ; Mice ; Phosphorylation ; Polymerase Chain Reaction ; Signal Transduction ; }, abstract = {The transcription factor GATA6 and the Fgf/Ras/MAPK signaling pathway are essential for the development of the primitive endoderm (PrE), one of the two lineages derived from the pluripotent inner cell mass (ICM) of mammalian blastocysts. A mutant mouse line in which Gata6-coding exons are replaced with H2BGFP (histone H2B Green Fluorescence Protein fusion protein) was developed to monitor Gata6 promoter activity. In the Gata6-H2BGFP heterozygous blastocysts, the ICM cells that initially had uniform GFP fluorescence signal at E3.5 diverged into two populations by the 64-cell stage, either as the GFP-high PrE or the GFP-low epiblasts (Epi). However in the GATA6-null blastocysts, the originally moderate GFP expression subsided in all ICM cells, indicating that the GATA6 protein is required to maintain its own promoter activity during PrE linage commitment. In embryonic stem cells, expressed GATA6 was shown to bind and activate the Gata6 promoter in PrE differentiation. Mutations of a conserved serine residue (S264) for Erk1/2 phosphorylation in GATA6 protein drastically impacted its ability to activate its own promoter. We conclude that phosphorylation of GATA6 by Erk1/2 compels exit from pluripotent state, and the phosphorylation propels a GATA6 positive feedback regulatory circuit to compel PrE differentiation. Our findings resolve the longstanding question on the dual requirements of GATA6 and Ras/MAPK pathway for PrE commitment of the pluripotent ICM.}, } @article {pmid29454705, year = {2018}, author = {Furlan, A and Adameyko, I}, title = {Schwann cell precursor: a neural crest cell in disguise?.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.02.008}, pmid = {29454705}, issn = {1095-564X}, abstract = {Schwann cell precursors (SCPs) are multipotent embryonic progenitors covering all developing peripheral nerves. These nerves grow and navigate with unprecedented precision, delivering SCP progenitors to almost all locations in the embryonic body. Within specific developing tissues, SCPs detach from nerves and generate neuroendocrine cells, autonomic neurons, mature Schwann cells, melanocytes and other cell types. These properties of SCPs evoke resemblances between them and their parental population, namely, neural crest cells. Neural crest cells are incredibly multipotent migratory cells that revolutionized the course of evolution in the lineage of early chordate animals. Given this similarity and recent data, it is possible to hypothesize that proto-neural crest cells are similar to SCPs spreading along the nerves. Here, we review the multipotency of SCPs, the signals that govern them, their potential therapeutic value, SCP's embryonic origin and their evolutionary connections. We dedicate this article to the memory of Wilhelm His, the father of the microtome and "Zwischenstrang", currently known as the neural crest.}, } @article {pmid29454669, year = {2018}, author = {Irving-Pease, EK and Frantz, LAF and Sykes, N and Callou, C and Larson, G}, title = {Rabbits and the Specious Origins of Domestication.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {149-152}, doi = {10.1016/j.tree.2017.12.009}, pmid = {29454669}, issn = {1872-8383}, mesh = {Animals ; Archaeology ; Biological Evolution ; *Domestication ; *Rabbits/genetics ; }, abstract = {Rabbits are commonly thought to have been domesticated in ∼AD600 by French monks. Using historical and archaeological records, and genetic methods, we demonstrate that this is a misconception and the general inability to date domestication stems from both methodological biases and the lack of appreciation of domestication as a continuum.}, } @article {pmid29454391, year = {2018}, author = {Mullaney, JA and Stephens, JE and Costello, ME and Fong, C and Geeling, BE and Gavin, PG and Wright, CM and Spector, TD and Brown, MA and Hamilton-Williams, EE}, title = {Type 1 diabetes susceptibility alleles are associated with distinct alterations in the gut microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {35}, pmid = {29454391}, issn = {2049-2618}, support = {APP1021324//National Health and Medical Research Council/International ; 2-2013-34/JDRF/Juvenile Diabetes Research Foundation/United States ; 3-PDF-2014-222-A-N/JDRF/Juvenile Diabetes Research Foundation/United States ; //Wellcome Trust/United Kingdom ; //Medical Research Council/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {Animals ; CTLA-4 Antigen/genetics ; Cation Transport Proteins/genetics ; Clostridiales/isolation & purification ; Diabetes Mellitus, Type 1/*genetics/immunology ; Dysbiosis/microbiology/*pathology ; Female ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*immunology/*microbiology ; Genetic Predisposition to Disease/genetics ; Humans ; Interleukin-2/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Ruminococcus/isolation & purification ; }, abstract = {BACKGROUND: Dysbiosis of the gut microbiota has been implicated in the pathogenesis of many autoimmune conditions including type 1 diabetes (T1D). It is unknown whether changes in the gut microbiota observed in T1D are due to environmental drivers, genetic risk factors, or both. Here, we have performed an analysis of associations between the gut microbiota and T1D genetic risk using the non-obese diabetic (NOD) mouse model of T1D and the TwinsUK cohort.

RESULTS: Through the analysis of five separate colonies of T1D susceptible NOD mice, we identified similarities in NOD microbiome that were independent of animal facility. Introduction of disease protective alleles at the Idd3 and Idd5 loci (IL2, Ctla4, Slc11a1, and Acadl) resulted in significant alterations in the NOD microbiome. Disease-protected strains exhibited a restoration of immune regulatory pathways within the gut which could also be reestablished using IL-2 therapy. Increased T1D disease risk from IL-2 pathway loci in the TwinsUK cohort of human subjects resulted in some similar microbiota changes to those observed in the NOD mouse.

CONCLUSIONS: These findings demonstrate for the first time that type 1 diabetes-associated genetic variants that restore immune tolerance to islet antigens also result in functional changes in the gut immune system and resultant changes in the microbiota.}, } @article {pmid29454387, year = {2018}, author = {Zhou, X and Stevens, MJA and Neuenschwander, S and Schwarm, A and Kreuzer, M and Bratus-Neuenschwander, A and Zeitz, JO}, title = {The transcriptome response of the ruminal methanogen Methanobrevibacter ruminantium strain M1 to the inhibitor lauric acid.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {135}, pmid = {29454387}, issn = {1756-0500}, mesh = {Animals ; Cell Culture Techniques ; Lauric Acids/*pharmacology ; Methane/*metabolism ; Methanobrevibacter/*drug effects/genetics ; Rumen/*microbiology ; Sequence Analysis, RNA ; Transcriptome/*drug effects ; }, abstract = {OBJECTIVE: Lauric acid (C12) is a medium-chain fatty acid that inhibits growth and production of the greenhouse gas methane by rumen methanogens such as Methanobrevibacter ruminantium. To understand the inhibitory mechanism of C12, a transcriptome analysis was performed in M. ruminantium strain M1 (DSM 1093) using RNA-Seq.

RESULTS: Pure cell cultures in the exponential growth phase were treated with 0.4 mg/ml C12, dissolved in dimethyl sulfoxide (DMSO), for 1 h and transcriptomic changes were compared to DMSO-only treated cells (final DMSO concentration 0.2%). Exposure to C12 resulted in differential expression of 163 of the 2280 genes in the M1 genome (maximum log2-fold change 6.6). Remarkably, C12 hardly affected the expression of genes involved in methanogenesis. Instead, most affected genes encode cell-surface associated proteins (adhesion-like proteins, membrane-associated transporters and hydrogenases), and proteins involved in detoxification or DNA-repair processes. Enrichment analysis on the genes regulated in the C12-treated group showed a significant enrichment for categories 'cell surface' and 'mobile elements' (activated by C12), and for the categories 'regulation' and 'protein fate' (represssed). These results are useful to generate and test specific hypotheses on the mechanism how C12 affects rumen methanogens.}, } @article {pmid29454355, year = {2018}, author = {Shu, W and Shen, X and Lei, P and Xiang, W and Ouyang, S and Yan, W}, title = {Temporal changes of fine root overyielding and foraging strategies in planted monoculture and mixed forests.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {9}, pmid = {29454355}, issn = {1472-6785}, support = {31200346//National Natural Science Foundation of China/International ; 31670448//National Natural Science Foundation of China/International ; }, abstract = {BACKGROUND: Mixed forests are believed to enhance ecosystem functioning and sustainability due to complementary resource use, environmental benefits and improved soil properties. The facilitation between different species may induce overyielding. Meanwhile, the species-specific fine root foraging strategies and tradeoffs would determine the structure and dynamics of plant communities. Here the aim was to investigate the admixing effects of fine-root biomass, vertical distribution and morphology in Pinus massoniana-Cinnamomum camphora mixed plantations and corresponding monocultures at 10-, 24- and 45-year old stands.

RESULTS: The fine root biomass in the Pinus-Cinnamomum mixed forest exerted a certain degree of overyielding effect. These positive admixing effects, however, did not enhance with forest stand development. The overall relative yield total ranged from 1.83 and 1.51 to 1.33 in 10-, 24- and 45-year-old stand, respectively. The overyielding was mainly attributed to the over-performance of late successional species, Cinnamomum, in mixed stands. The vertical fine root biomass distribution model showed fine roots of pioneer species, Pinus, shifted to the superficial layer when mixed with Cinnamomum. Furthermore, the specific root length (SRL) of Pinus was significantly higher in Pinus-Cinnamomum mixed stands than that in monocultures, and the magnitude of differences increased over time. However, the vertical fine-root distribution and SRL for Cinnamomum did not show significant differences between monoculture and mixtures.

CONCLUSIONS: Our results indicated that the magnitude of fine root overyielding in mixed forests showed a high degree of consistency with the total amount of fine root biomass itself, suggesting the overyielding effects in mixed forests were correlated with the degree of belowground interaction and competition degree involved. The late successional species, Cinnamomum, invested more carbon to belowground by increasing the fine root biomass in mixtures. While the pioneer species, Pinus, adapted to the presence of the species Cinnamomum by modification of vertical distribution and root morphological plasticity in the mixtures. These species-specific fine root foraging strategies might imply the differences of forest growth strategies of co-occurring species and contribute to the success and failure of particular species during the succession over time.}, } @article {pmid29454313, year = {2018}, author = {Arias-Carrasco, R and Vásquez-Morán, Y and Nakaya, HI and Maracaja-Coutinho, V}, title = {StructRNAfinder: an automated pipeline and web server for RNA families prediction.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {55}, pmid = {29454313}, issn = {1471-2105}, support = {11161020//Comisión Nacional de Investigación Científica y Tecnológica/International ; PAI79170021//Comisión Nacional de Investigación Científica y Tecnológica/International ; 15130011//Comisión Nacional de Investigación Científica y Tecnológica/International ; 16BPE-62321//Corporación de Fomento de la Producción (CL)/International ; 14-SSAF-27061-9//Corporación de Fomento de la Producción/International ; 12/19278-6//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; }, mesh = {Automation ; Computational Biology/*methods ; *Internet ; RNA/chemistry/classification/*genetics ; *Software ; Workflow ; }, abstract = {BACKGROUND: The function of many noncoding RNAs (ncRNAs) depend upon their secondary structures. Over the last decades, several methodologies have been developed to predict such structures or to use them to functionally annotate RNAs into RNA families. However, to fully perform this analysis, researchers should utilize multiple tools, which require the constant parsing and processing of several intermediate files. This makes the large-scale prediction and annotation of RNAs a daunting task even to researchers with good computational or bioinformatics skills.

RESULTS: We present an automated pipeline named StructRNAfinder that predicts and annotates RNA families in transcript or genome sequences. This single tool not only displays the sequence/structural consensus alignments for each RNA family, according to Rfam database but also provides a taxonomic overview for each assigned functional RNA. Moreover, we implemented a user-friendly web service that allows researchers to upload their own nucleotide sequences in order to perform the whole analysis. Finally, we provided a stand-alone version of StructRNAfinder to be used in large-scale projects. The tool was developed under GNU General Public License (GPLv3) and is freely available at http://structrnafinder.integrativebioinformatics.me .

CONCLUSIONS: The main advantage of StructRNAfinder relies on the large-scale processing and integrating the data obtained by each tool and database employed along the workflow, of which several files are generated and displayed in user-friendly reports, useful for downstream analyses and data exploration.}, } @article {pmid29454312, year = {2018}, author = {Shi, H and Zhang, J and Li, S and Ji, S and Cao, Z and Zhang, H and Wang, Y}, title = {Effects of a wide range of dietary forage-to-concentrate ratios on nutrient utilization and hepatic transcriptional profiles in limit-fed Holstein heifers.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {148}, pmid = {29454312}, issn = {1471-2164}, support = {31402099//National Nature Science Foundation/International ; CARS-37//National Dairy Industry and Technology System/International ; S2016G4513//National Key R&D Program of China/International ; }, mesh = {Animal Nutritional Physiological Phenomena ; Animals ; Cattle/growth & development/*physiology ; Diet/*veterinary ; Fermentation ; Gene Expression Profiling/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Liver/*metabolism ; Rumen/*metabolism ; }, abstract = {BACKGROUND: Improving the efficiency of animal production is a relentless pursuit of ruminant producers. Energy utilization and partition can be affected by dietary composition and nutrient availability. Furthermore, the liver is the central metabolic intersection in cattle. However, the specific metabolic changes in the liver under conditions of limit-feeding remain unclear and require further study. The present study aimed to elucidate the effects of a wide range of dietary forage:concentrate ratios (F:C) on energy utilization, and identify potential changes in molecular metabolism by analyzing hepatic transcriptional profiles. Twenty-four half-sib Holstein heifers were fed four F:C diets (20:80, 40:60, 60:40, and 80:20 on a dry matter basis), with similar intake levels of metabolizable energy (ME) and crude protein. Liver biopsy samples were obtained and RNA sequencing was conducted to identify the hepatic transcriptomic changes. Moreover, the ruminal fermentation profiles, growth characteristics, and levels of metabolites in the liver and plasma of the heifers were monitored.

RESULTS: The proportion of acetate showed a linear increase (P < 0.01) with increasing dietary forage levels, whereas the proportion of propionate showed a linear decline (P ≤ 0.01). Lower levels of average daily gain and feed efficiency (P < 0.01) were observed in heifers fed high levels of forage, with a significant linear response. Using the Short Time-series Expression Miner software package, the expression trends of significant differentially expressed genes (DEGs) were generally divided into 20 clusters, according to their dynamic expression patterns. Functional classification analysis showed that lipid metabolism (particularly cholesterol and steroid metabolism which were in line with the cholesterol content in the liver and plasma) was significantly increased with increasing dietary forage levels and slightly reduced by the 80% forage diet. Nine DEGs were enriched in the related pathways, namely HMGCS1, HMGCR, MSMO1, MVK, MVD, IDI1, FDPS, LSS, and DHCR7.

CONCLUSIONS: The ruminal fermentation and feed efficiency results suggest that different mechanisms of energy utilization might occur in heifers fed different F:C diets with similar levels of ME intake. Increased cholesterol synthesis from acetate might be responsible for the reduced efficiency of energy utilization in heifers fed high-forage diets.}, } @article {pmid29454308, year = {2018}, author = {Jiao, H and Liu, X and Sun, S and Wang, P and Qiao, X and Li, J and Tang, C and Wu, J and Zhang, S and Tao, S}, title = {The unique evolutionary pattern of the Hydroxyproline-rich glycoproteins superfamily in Chinese white pear (Pyrus bretschneideri).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {36}, pmid = {29454308}, issn = {1471-2229}, support = {950000//NO.31471839/ ; }, mesh = {Biological Evolution ; Gene Duplication/genetics/physiology ; Glycoproteins/*chemistry ; Hydroxyproline/*chemistry ; Pyrus/genetics/*metabolism ; }, abstract = {BACKGROUND: The hydroxyproline-rich glycoprotein (HRGP) superfamily, comprising three families (arabinogalactan-proteins, AGPs; extensins, EXTs; proline-rich proteins, PRPs), is a class of proline-rich proteins that exhibit high diversity and are involved in many aspects of plant biology.

RESULTS: In this study, 838 HRGPs were identified from Chinese white pear (Pyrus bretschneideri) by searching for biased amino acid composition and conserved motifs. 405 HRGPs were derived from whole genome duplication (WGD) events which is suggested to be the major force of driving HRGPs expansion and the recent WGD event shared by apple and pear generated most duplicated HRGPs in pear. This duplication event drived the structural variation of the HRGPs encoding hydroxyproline (Hyp)-rich motifs. The rate of HRGPs evolution mainly impacted the Hyp-rich motifs even in chimeric HRGPs. During the evolution of 53 PRPs that are also typified by 7-deoxyloganetin glucosyltransferase-like genes, the duplication from PRP to non-PRP was indirectly modified by positive selection. These results suggested that the rate of HRGP evolution mainly influenced the Hyp-rich motifs even in chimeric HRGPs. The expression divergence of HRGPs was higher than that of other commonly duplicated genes. In pear pistil, 601 HRGPs exhibited expression, while in pear pollen, 285 HRGPs were expressed. The qPCR results revealed that Pbr036330.1 and Pbr010506.1 showed different expression profile in self-incompatibility of pear pistil.

CONCLUSIONS: The researches indicated that WGD events was the main duplication type during the evolution of HRGPs, and the highly variable Hyp-motifs might be accountable for the expansion, evolution and expression divergence of HRGPs and that this divergence may be responsible for the gain of new functions in plants.}, } @article {pmid29454192, year = {2018}, author = {Wang, Y and Wang, Y}, title = {Phytophthora sojae effectors orchestrate warfare with host immunity.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {7-13}, doi = {10.1016/j.mib.2018.01.008}, pmid = {29454192}, issn = {1879-0364}, abstract = {Phytophthora sojae is one of the most damaging plant pathogens of soybean. To aid establishment of a compatible interaction with its host, P. sojae deploys many secreted effectors. These effectors act either in the apoplastic space to cope with hostile conditions or inside of host cells to reprogram host physiology favoring pathogen growth. Effectors have been used as molecular probes, which revealed in Phytophthora that effectors execute their virulence function via manipulating host targets. In addition, recent studies have discovered 'pseudo-effectors' in Phytophthora that act as decoys to shield virulence effectors from host defense, a new paradigm in plant-pathogen interactions.}, } @article {pmid29454191, year = {2018}, author = {Lorrain, C and Petre, B and Duplessis, S}, title = {Show me the way: rust effector targets in heterologous plant systems.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {19-25}, doi = {10.1016/j.mib.2018.01.016}, pmid = {29454191}, issn = {1879-0364}, abstract = {For years, the study of rust fungal effectors has been impeded by the lack of molecular genetic tools in rust pathosystems. The recent use of heterologous plants to perform effector screens (effectoromics)-including effector localisation (cellular targets) and protein interactors (molecular targets) in plant cells-has changed the game. These screens revealed that many candidate effectors from various rust fungi target specific plant cell compartments, including chloroplasts, and associate with specific plant protein complexes. Such information represents unparalleled opportunities to understand how effectors sustain extreme parasitic interactions and obligate biotrophy. Despite their limitations, we here portray how the use of heterologous expression systems has been essential for gaining new insight into rust effectors.}, } @article {pmid29454026, year = {2018}, author = {Westphal, LL and Lau, J and Negro, Z and Moreno, IJ and Ismail Mohammed, W and Lee, H and Tang, H and Finkel, SE and Kram, KE}, title = {Adaptation of Escherichia coli to long-term batch culture in various rich media.}, journal = {Research in microbiology}, volume = {169}, number = {3}, pages = {145-156}, doi = {10.1016/j.resmic.2018.01.003}, pmid = {29454026}, issn = {1769-7123}, mesh = {*Adaptation, Biological ; Alleles ; *Batch Cell Culture Techniques ; *Culture Media ; Epistasis, Genetic ; Escherichia coli/*physiology ; Gene Frequency ; Gene-Environment Interaction ; Genetic Fitness ; Genetic Variation ; Mutation ; *Nutritional Physiological Phenomena ; }, abstract = {Experimental evolution studies have characterized the genetic strategies microbes utilize to adapt to their environments, mainly focusing on how microbes adapt to constant and/or defined environments. Using a system that incubates Escherichia coli in different complex media in long-term batch culture, we have focused on how heterogeneity and environment affects adaptive landscapes. In this system, there is no passaging of cells, and therefore genetic diversity is lost only through negative selection, without the experimentally-imposed bottlenecking common in other platforms. In contrast with other experimental evolution systems, because of cycling of nutrients and waste products, this is a heterogeneous environment, where selective pressures change over time, similar to natural environments. We determined that incubation in each environment leads to different adaptations by observing the growth advantage in stationary phase (GASP) phenotype. Re-sequencing whole genomes of populations identified both mutant alleles in a conserved set of genes and differences in evolutionary trajectories between environments. Reconstructing identified mutations in the parental strain background confirmed the adaptive advantage of some alleles, but also identified a surprising number of neutral or even deleterious mutations. This result indicates that complex epistatic interactions may be under positive selection within these heterogeneous environments.}, } @article {pmid29453943, year = {2018}, author = {Dinsmore, CJ and Soriano, P}, title = {MAPK and PI3K signaling: At the crossroads of neural crest development.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29453943}, issn = {1095-564X}, support = {F32 DE026678/DE/NIDCR NIH HHS/United States ; R01 DE022363/DE/NIDCR NIH HHS/United States ; R01 DE022778/DE/NIDCR NIH HHS/United States ; }, abstract = {Receptor tyrosine kinase-mediated growth factor signaling is essential for proper formation and development of the neural crest. The many ligands and receptors implicated in these processes signal through relatively few downstream pathways, frequently converging on the MAPK and PI3K pathways. Despite decades of study, there is still considerable uncertainty about where and when these signaling pathways are required and how they elicit particular responses. This review summarizes our current understanding of growth factor-induced MAPK and PI3K signaling in the neural crest.}, } @article {pmid29453352, year = {2018}, author = {Manning, P and van der Plas, F and Soliveres, S and Allan, E and Maestre, FT and Mace, G and Whittingham, MJ and Fischer, M}, title = {Redefining ecosystem multifunctionality.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {427-436}, doi = {10.1038/s41559-017-0461-7}, pmid = {29453352}, issn = {2397-334X}, abstract = {Recent years have seen a surge of interest in ecosystem multifunctionality, a concept that has developed in the largely separate fields of biodiversity-ecosystem function and land management research. Here we discuss the merit of the multifunctionality concept, the advances it has delivered, the challenges it faces and solutions to these challenges. This involves the redefinition of multifunctionality as a property that exists at two levels: ecosystem function multifunctionality and ecosystem service multifunctionality. The framework presented provides a road map for the development of multifunctionality measures that are robust, quantifiable and relevant to both fundamental ecological science and ecosystem management.}, } @article {pmid29453351, year = {2018}, author = {}, title = {Resistance is … complex.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {405}, doi = {10.1038/s41559-018-0495-5}, pmid = {29453351}, issn = {2397-334X}, } @article {pmid29453350, year = {2018}, author = {Culina, A and Baglioni, M and Crowther, TW and Visser, ME and Woutersen-Windhouwer, S and Manghi, P}, title = {Navigating the unfolding open data landscape in ecology and evolution.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {420-426}, doi = {10.1038/s41559-017-0458-2}, pmid = {29453350}, issn = {2397-334X}, abstract = {Open access to data is revolutionizing the sciences. To allow ecologists and evolutionary biologists to confidently find and use the existing data, we provide an overview of the landscape of online data infrastructures, and highlight the key points to consider when using open data. We introduce an online collaborative platform to keep a community-driven, updated list of the best sources that enable search for data in one interface. In doing so, our aim is to lower the barrier to accessing open data, and encourage its use by researchers hoping to increase the scope, reliability and value of their findings.}, } @article {pmid29453278, year = {2018}, author = {Hong, X and Sullivan, RJ and Kalinich, M and Kwan, TT and Giobbie-Hurder, A and Pan, S and LiCausi, JA and Milner, JD and Nieman, LT and Wittner, BS and Ho, U and Chen, T and Kapur, R and Lawrence, DP and Flaherty, KT and Sequist, LV and Ramaswamy, S and Miyamoto, DT and Lawrence, M and Toner, M and Isselbacher, KJ and Maheswaran, S and Haber, DA}, title = {Molecular signatures of circulating melanoma cells for monitoring early response to immune checkpoint therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2467-2472}, pmid = {29453278}, issn = {1091-6490}, support = {F30 CA224588/CA/NCI NIH HHS/United States ; R01 CA129933/CA/NCI NIH HHS/United States ; U01 EB012493/EB/NIBIB NIH HHS/United States ; R01 EB008047/EB/NIBIB NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; }, mesh = {*Antineoplastic Agents, Immunological/pharmacology/therapeutic use ; Biomarkers, Tumor/*blood/chemistry ; Cell- and Tissue-Based Therapy ; Female ; Humans ; Kaplan-Meier Estimate ; Liquid Biopsy ; Male ; *Melanoma/blood/diagnosis/drug therapy/mortality ; Middle Aged ; *Neoplastic Cells, Circulating/chemistry/drug effects ; RNA/analysis/genetics/metabolism ; *Skin Neoplasms/blood/diagnosis/drug therapy/mortality ; }, abstract = {A subset of patients with metastatic melanoma have sustained remissions following treatment with immune checkpoint inhibitors. However, analyses of pretreatment tumor biopsies for markers predictive of response, including PD-1 ligand (PD-L1) expression and mutational burden, are insufficiently precise to guide treatment selection, and clinical radiographic evidence of response on therapy may be delayed, leading to some patients receiving potentially ineffective but toxic therapy. Here, we developed a molecular signature of melanoma circulating tumor cells (CTCs) to quantify early tumor response using blood-based monitoring. A quantitative 19-gene digital RNA signature (CTC score) applied to microfluidically enriched CTCs robustly distinguishes melanoma cells, within a background of blood cells in reconstituted and in patient-derived (n = 42) blood specimens. In a prospective cohort of 49 patients treated with immune checkpoint inhibitors, a decrease in CTC score within 7 weeks of therapy correlates with marked improvement in progression-free survival [hazard ratio (HR), 0.17; P = 0.008] and overall survival (HR, 0.12; P = 0.04). Thus, digital quantitation of melanoma CTC-derived transcripts enables serial noninvasive monitoring of tumor burden, supporting the rational application of immune checkpoint inhibition therapies.}, } @article {pmid29453277, year = {2018}, author = {Borel, F and Sun, H and Zieger, M and Cox, A and Cardozo, B and Li, W and Oliveira, G and Davis, A and Gruntman, A and Flotte, TR and Brodsky, MH and Hoffman, AM and Elmallah, MK and Mueller, C}, title = {Editing out five Serpina1 paralogs to create a mouse model of genetic emphysema.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {2788-2793}, pmid = {29453277}, issn = {1091-6490}, support = {P01 HL131471/HL/NHLBI NIH HHS/United States ; R01 DK098252/DK/NIDDK NIH HHS/United States ; K08 HD077040/HD/NICHD NIH HHS/United States ; R01 NS088689/NS/NINDS NIH HHS/United States ; R24 OD018259/OD/NIH HHS/United States ; R21 NS098131/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Female ; Humans ; Liver/metabolism ; Lung/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pulmonary Emphysema/*genetics/metabolism ; alpha 1-Antitrypsin/*genetics/metabolism ; }, abstract = {Chronic obstructive pulmonary disease affects 10% of the worldwide population, and the leading genetic cause is α-1 antitrypsin (AAT) deficiency. Due to the complexity of the murine locus, which includes up to six Serpina1 paralogs, no genetic animal model of the disease has been successfully generated until now. Here we create a quintuple Serpina1a-e knockout using CRISPR/Cas9-mediated genome editing. The phenotype recapitulates the human disease phenotype, i.e., absence of hepatic and circulating AAT translates functionally to a reduced capacity to inhibit neutrophil elastase. With age, Serpina1 null mice develop emphysema spontaneously, which can be induced in younger mice by a lipopolysaccharide challenge. This mouse models not only AAT deficiency but also emphysema and is a relevant genetic model and not one based on developmental impairment of alveolarization or elastase administration. We anticipate that this unique model will be highly relevant not only to the preclinical development of therapeutics for AAT deficiency, but also to emphysema and smoking research.}, } @article {pmid29453276, year = {2018}, author = {Weeks, AM and Wang, N and Pelton, JG and Chang, MCY}, title = {Entropy drives selective fluorine recognition in the fluoroacetyl-CoA thioesterase from Streptomyces cattleya.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2193-E2201}, pmid = {29453276}, issn = {1091-6490}, support = {P41 GM068933/GM/NIGMS NIH HHS/United States ; R01 GM123181/GM/NIGMS NIH HHS/United States ; T32 GM066698/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetyl Coenzyme A/*chemistry/*metabolism ; Bacterial Proteins/chemistry/metabolism ; Catalytic Domain ; Entropy ; Fluorine/*chemistry/*metabolism ; Nuclear Magnetic Resonance, Biomolecular ; Phenylalanine/chemistry ; Protein Binding ; Streptomyces/*enzymology ; Substrate Specificity ; }, abstract = {Fluorinated small molecules play an important role in the design of bioactive compounds for a broad range of applications. As such, there is strong interest in developing a deeper understanding of how fluorine affects the interaction of these ligands with their targets. Given the small number of fluorinated metabolites identified to date, insights into fluorine recognition have been provided almost entirely by synthetic systems. The fluoroacetyl-CoA thioesterase (FlK) from Streptomyces cattleya thus provides a unique opportunity to study an enzyme-ligand pair that has been evolutionarily optimized for a surprisingly high 106 selectivity for a single fluorine substituent. In these studies, we synthesize a series of analogs of fluoroacetyl-CoA and acetyl-CoA to generate nonhydrolyzable ester, amide, and ketone congeners of the thioester substrate to isolate the role of fluorine molecular recognition in FlK selectivity. Using a combination of thermodynamic, kinetic, and protein NMR experiments, we show that fluorine recognition is entropically driven by the interaction of the fluorine substituent with a key residue, Phe-36, on the lid structure that covers the active site, resulting in an ∼5- to 20-fold difference in binding (KD). Although the magnitude of discrimination is similar to that found in designed synthetic ligand-protein complexes where dipolar interactions control fluorine recognition, these studies show that hydrophobic and solvation effects serve as the major determinant of naturally evolved fluorine selectivity.}, } @article {pmid29453275, year = {2018}, author = {Korczynska, M and Clark, MJ and Valant, C and Xu, J and Moo, EV and Albold, S and Weiss, DR and Torosyan, H and Huang, W and Kruse, AC and Lyda, BR and May, LT and Baltos, JA and Sexton, PM and Kobilka, BK and Christopoulos, A and Shoichet, BK and Sunahara, RK}, title = {Structure-based discovery of selective positive allosteric modulators of antagonists for the M2 muscarinic acetylcholine receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2419-E2428}, pmid = {29453275}, issn = {1091-6490}, support = {R35 GM122481/GM/NIGMS NIH HHS/United States ; U19 GM106990/GM/NIGMS NIH HHS/United States ; }, mesh = {Allosteric Regulation ; Allosteric Site ; Animals ; Humans ; Kinetics ; Ligands ; Mitogen-Activated Protein Kinase 1/metabolism ; Mitogen-Activated Protein Kinase 3/metabolism ; Molecular Docking Simulation ; Muscarinic Agonists/*chemistry/metabolism ; Phosphorylation ; Protein Binding ; Rats ; Receptor, Muscarinic M2/*chemistry/metabolism ; }, abstract = {Subtype-selective antagonists for muscarinic acetylcholine receptors (mAChRs) have long been elusive, owing to the highly conserved orthosteric binding site. However, allosteric sites of these receptors are less conserved, motivating the search for allosteric ligands that modulate agonists or antagonists to confer subtype selectivity. Accordingly, a 4.6 million-molecule library was docked against the structure of the prototypical M2 mAChR, seeking molecules that specifically stabilized antagonist binding. This led us to identify a positive allosteric modulator (PAM) that potentiated the antagonist N-methyl scopolamine (NMS). Structure-based optimization led to compound '628, which enhanced binding of NMS, and the drug scopolamine itself, with a cooperativity factor (α) of 5.5 and a KB of 1.1 μM, while sparing the endogenous agonist acetylcholine. NMR spectral changes determined for methionine residues reflected changes in the allosteric network. Moreover, '628 slowed the dissociation rate of NMS from the M2 mAChR by 50-fold, an effect not observed at the other four mAChR subtypes. The specific PAM effect of '628 on NMS antagonism was conserved in functional assays, including agonist stimulation of [35S]GTPγS binding and ERK 1/2 phosphorylation. Importantly, the selective allostery between '628 and NMS was retained in membranes from adult rat hypothalamus and in neonatal rat cardiomyocytes, supporting the physiological relevance of this PAM/antagonist approach. This study supports the feasibility of discovering PAMs that confer subtype selectivity to antagonists; molecules like '628 can convert an armamentarium of potent but nonselective GPCR antagonist drugs into subtype-selective reagents, thus reducing their off-target effects.}, } @article {pmid29453274, year = {2018}, author = {Burghardt, LT and Epstein, B and Guhlin, J and Nelson, MS and Taylor, MR and Young, ND and Sadowsky, MJ and Tiffin, P}, title = {Select and resequence reveals relative fitness of bacteria in symbiotic and free-living environments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2425-2430}, pmid = {29453274}, issn = {1091-6490}, mesh = {Bacterial Physiological Phenomena ; *Genetic Fitness/genetics/physiology ; Genetic Variation ; *Medicago/microbiology/physiology ; Nitrogen Fixation ; Phenotype ; Rhizome/microbiology ; *Sinorhizobium meliloti/genetics/physiology ; *Soil Microbiology ; *Symbiosis ; Synthetic Biology ; }, abstract = {Assays to accurately estimate relative fitness of bacteria growing in multistrain communities can advance our understanding of how selection shapes diversity within a lineage. Here, we present a variant of the "evolve and resequence" approach both to estimate relative fitness and to identify genetic variants responsible for fitness variation of symbiotic bacteria in free-living and host environments. We demonstrate the utility of this approach by characterizing selection by two plant hosts and in two free-living environments (sterilized soil and liquid media) acting on synthetic communities of the facultatively symbiotic bacterium Ensifer meliloti We find (i) selection that hosts exert on rhizobial communities depends on competition among strains, (ii) selection is stronger inside hosts than in either free-living environment, and (iii) a positive host-dependent relationship between relative strain fitness in multistrain communities and host benefits provided by strains in single-strain experiments. The greatest changes in allele frequencies in response to plant hosts are in genes associated with motility, regulation of nitrogen fixation, and host/rhizobia signaling. The approach we present provides a powerful complement to experimental evolution and forward genetic screens for characterizing selection in bacterial populations, identifying gene function, and surveying the functional importance of naturally occurring genomic variation.}, } @article {pmid29453124, year = {2018}, author = {Wong-Ng, J and Celani, A and Vergassola, M}, title = {Exploring the function of bacterial chemotaxis.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {16-21}, doi = {10.1016/j.mib.2018.01.010}, pmid = {29453124}, issn = {1879-0364}, abstract = {Bacterial chemotaxis is a classical subject: our knowledge of its molecular pathway has grown very detailed, and experimental observations, as well as mathematical models of the dynamics of chemotactic populations, have a history of several decades. This should not lead to the conclusion that only minor details are left to be understood. Indeed, it is believed that bacterial chemotaxis is under selection for efficiency, yet the underlying functional forces remain largely unknown. These aspects are discussed here by the presentation of illustrative examples related to the role of adaptation and signal integration. Both are expected to be important in ecologically relevant conditions, where chemotaxis should be strongly coupled with metabolism and growth, due to the presence of diverse chemoattractant cues and their active consumption by multiple types of bacteria competing for growth.}, } @article {pmid29452953, year = {2018}, author = {Albers, SV and Jarrell, KF}, title = {The Archaellum: An Update on the Unique Archaeal Motility Structure.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {351-362}, doi = {10.1016/j.tim.2018.01.004}, pmid = {29452953}, issn = {1878-4380}, abstract = {Each of the three domains of life exhibits a unique motility structure: while Bacteria use flagella, Eukarya employ cilia, and Archaea swim using archaella. Since the new name for the archaeal motility structure was proposed, in 2012, a significant amount of new data on the regulation of transcription of archaella operons, the structure and function of archaellum subunits, their interactions, and cryo-EM data on in situ archaellum complexes in whole cells have been obtained. These data support the notion that the archaellum is evolutionary and structurally unrelated to the flagellum, but instead is related to archaeal and bacterial type IV pili and emphasize that it is a motility structure unique to the Archaea.}, } @article {pmid29452952, year = {2018}, author = {Atack, JM and Tan, A and Bakaletz, LO and Jennings, MP and Seib, KL}, title = {Phasevarions of Bacterial Pathogens: Methylomics Sheds New Light on Old Enemies.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {715-726}, pmid = {29452952}, issn = {1878-4380}, support = {R01 DC015688/DC/NIDCD NIH HHS/United States ; }, abstract = {A wide variety of bacterial pathogens express phase-variable DNA methyltransferases that control expression of multiple genes via epigenetic mechanisms. These randomly switching regulons - phasevarions - regulate genes involved in pathogenesis, host adaptation, and antibiotic resistance. Individual phase-variable genes can be identified in silico as they contain easily recognized features such as simple sequence repeats (SSRs) or inverted repeats (IRs) that mediate the random switching of expression. Conversely, phasevarion-controlled genes do not contain any easily identifiable features. The study of DNA methyltransferase specificity using Single-Molecule, Real-Time (SMRT) sequencing and methylome analysis has rapidly advanced the analysis of phasevarions by allowing methylomics to be combined with whole-transcriptome/proteome analysis to comprehensively characterize these systems in a number of important bacterial pathogens.}, } @article {pmid29452951, year = {2018}, author = {Chassaing, B and Cascales, E}, title = {Antibacterial Weapons: Targeted Destruction in the Microbiota.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {329-338}, doi = {10.1016/j.tim.2018.01.006}, pmid = {29452951}, issn = {1878-4380}, abstract = {The intestinal microbiota plays an important role in health, particularly in promoting intestinal metabolic capacity and in maturing the immune system. The intestinal microbiota also mediates colonization resistance against pathogenic bacteria, hence protecting the host from infections. In addition, some bacterial pathogens deliver toxins that target phylogenetically related or distinct bacterial species in order to outcompete and establish within the microbiota. The most widely distributed weapons include bacteriocins, as well as contact-dependent growth inhibition and type VI secretion systems. In this review, we discuss important advances about the impact of such antibacterial systems on shaping the intestinal microbiota.}, } @article {pmid29452950, year = {2018}, author = {Hopke, A and Brown, AJP and Hall, RA and Wheeler, RT}, title = {Dynamic Fungal Cell Wall Architecture in Stress Adaptation and Immune Evasion.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {284-295}, pmid = {29452950}, issn = {1878-4380}, support = {//Wellcome Trust/United Kingdom ; MR/L00903X/1//Medical Research Council/United Kingdom ; R15 AI133415/AI/NIAID NIH HHS/United States ; BB/K017365/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/M026663/1//Medical Research Council/United Kingdom ; 097377//Wellcome Trust/United Kingdom ; }, abstract = {Deadly infections from opportunistic fungi have risen in frequency, largely because of the at-risk immunocompromised population created by advances in modern medicine and the HIV/AIDS pandemic. This review focuses on dynamics of the fungal polysaccharide cell wall, which plays an outsized role in fungal pathogenesis and therapy because it acts as both an environmental barrier and as the major interface with the host immune system. Human fungal pathogens use architectural strategies to mask epitopes from the host and prevent immune surveillance, and recent work elucidates how biotic and abiotic stresses present during infection can either block or enhance masking. The signaling components implicated in regulating fungal immune recognition can teach us how cell wall dynamics are controlled, and represent potential targets for interventions designed to boost or dampen immunity.}, } @article {pmid29452845, year = {2018}, author = {McDonald, MC and Solomon, PS}, title = {Just the surface: advances in the discovery and characterization of necrotrophic wheat effectors.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {14-18}, doi = {10.1016/j.mib.2018.01.019}, pmid = {29452845}, issn = {1879-0364}, abstract = {For many years pathogens of wheat have remained poorly understood. Hindered by an inaccessible host and the obligate nature of many of the pathogens, our understanding of these interactions has been limited compared to other more amenable pathosystems. However, breakthroughs over recent years have shed new light on diseases of wheat, particularly those caused by the genetically tractable necrotrophic pathogens. We now understand that many of the necrotrophic fungal pathogens do interact with wheat in a strict gene-for-gene relationship, and that pathogen and host partners in these interactions have now been identified. This improved understanding of necrotrophic effector biology has fundamentally changed the way we consider these important wheat diseases.}, } @article {pmid29452844, year = {2018}, author = {Shen, Q and Liu, Y and Naqvi, NI}, title = {Fungal effectors at the crossroads of phytohormone signaling.}, journal = {Current opinion in microbiology}, volume = {46}, number = {}, pages = {1-6}, doi = {10.1016/j.mib.2018.01.006}, pmid = {29452844}, issn = {1879-0364}, abstract = {Phytohormone networks are crucial for maintaining the delicate balance between growth and biotic stress responses in plants. Jasmonic acid, salicylic acid, ethylene, and the associated signaling crosstalk are important for pathogen defense; whereas gibberellin and cytokinin function in growth and development in plants. Plant pathogenic fungi have evolved remarkable strategies to manipulate and/or hijack such phytohormone signaling cascades for their own benefit, thus leading to susceptibility and disease in host plants. Interestingly, these hormones are also targeted by fungal endosymbionts and mutualists during beneficial interactions with plants. We highlight current advances in our understanding of the role of fungal effectors in such antagonistic manipulation of phytohormones during pathogenic as well as symbiotic association with plant hosts. In addition to the aforementioned effector-based control, certain phytohormone mimics have recently emerged as a powerful molecular language in fungal manipulation of defense responses and innate immunity in plants.}, } @article {pmid29452597, year = {2018}, author = {Kabogo, J and Muniu, E and Wamunyokoli, F and Musoke, R and Songok, E}, title = {Evidence of reduced treatment adherence among HIV infected paediatric and adolescent populations in Nairobi at the onset of the UNAIDS Universal Test and Treat Program.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {134}, pmid = {29452597}, issn = {1756-0500}, mesh = {Adolescent ; Anti-HIV Agents/*therapeutic use ; Child ; Child, Preschool ; Female ; HIV Infections/*drug therapy/*ethnology ; Humans ; Infant ; Kenya ; Male ; Medication Adherence/*ethnology ; *Outcome Assessment (Health Care) ; *Program Development ; Retrospective Studies ; *United Nations ; *World Health Organization ; }, abstract = {OBJECTIVE: We conducted a retrospective cohort study to evaluate the efficacy of the World Health Organization (WHO) "Universal Test and Treat" (UTT) policy, initiated in Kenya in September 2016. Under this policy, every human immunodeficiency virus (HIV)-infected person should be initiated on antiretroviral therapy (ART). We compared intra- and inter-group viral suppression and ART adherence rates for pre-UTT (initiated on ART in March-August 2016) and UTT groups (initiated in September 2016). The study was conducted in a community outreach Program in Nairobi with 3500 HIV-infected children enrolled.

RESULTS: 122 children and adolescents were initiated on first-line ART pre-UTT, and 197 during the UTT period. The 6 month viral suppression rate was 79.7% pre-UTT versus 76.6% UTT (P < 0.05). Suboptimal adherence was higher in the UTT than pre-UTT period (88 of 197, 44.7% and 44 of 122, 34%; P < 0.001). The decrease in adherence was greater among orphans (91.7% pre-UTT and 87.2% UTT, P = 0.001) and children 11-18 years. Our results show that successful implementation of the UTT policy in Africa is challenged by an increased risk of suboptimal adherence. There is a need to develop extra strategies to support adherence, especially among orphans and teenagers.}, } @article {pmid29452359, year = {2018}, author = {Méric, G and McNally, A and Pessia, A and Mourkas, E and Pascoe, B and Mageiros, L and Vehkala, M and Corander, J and Sheppard, SK}, title = {Convergent Amino Acid Signatures in Polyphyletic Campylobacter jejuni Subpopulations Suggest Human Niche Tropism.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {763-774}, pmid = {29452359}, issn = {1759-6653}, support = {//Wellcome Trust/United Kingdom ; MR/L015080/1//Medical Research Council/United Kingdom ; 088786/C/09/Z//Wellcome Trust/United Kingdom ; BB/I02464X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Campylobacter Infections/*microbiology ; Campylobacter jejuni/genetics/*isolation & purification/pathogenicity ; Chickens/genetics/microbiology ; Genetic Variation ; Genotype ; Host-Pathogen Interactions/*genetics ; Humans ; Multilocus Sequence Typing ; *Phylogeny ; Poultry/microbiology ; }, abstract = {Human infection with the gastrointestinal pathogen Campylobacter jejuni is dependent upon the opportunity for zoonotic transmission and the ability of strains to colonize the human host. Certain lineages of this diverse organism are more common in human infection but the factors underlying this overrepresentation are not fully understood. We analyzed 601 isolate genomes from agricultural animals and human clinical cases, including isolates from the multihost (ecological generalist) ST-21 and ST-45 clonal complexes (CCs). Combined nucleotide and amino acid sequence analysis identified 12 human-only amino acid KPAX clusters among polyphyletic lineages within the common disease causing CC21 group isolates, with no such clusters among CC45 isolates. Isolate sequence types within human-only CC21 group KPAX clusters have been sampled from other hosts, including poultry, so rather than representing unsampled reservoir hosts, the increase in relative frequency in human infection potentially reflects a genetic bottleneck at the point of human infection. Consistent with this, sequence enrichment analysis identified nucleotide variation in genes with putative functions related to human colonization and pathogenesis, in human-only clusters. Furthermore, the tight clustering and polyphyly of human-only lineage clusters within a single CC suggest the repeated evolution of human association through acquisition of genetic elements within this complex. Taken together, combined nucleotide and amino acid analysis of large isolate collections may provide clues about human niche tropism and the nature of the forces that promote the emergence of clinically important C. jejuni lineages.}, } @article {pmid29452355, year = {2018}, author = {Chevignon, G and Boyd, BM and Brandt, JW and Oliver, KM and Strand, MR}, title = {Culture-Facilitated Comparative Genomics of the Facultative Symbiont Hamiltonella defensa.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {786-802}, pmid = {29452355}, issn = {1759-6653}, mesh = {Animals ; Aphids/*microbiology/parasitology ; Bacteriophages/genetics ; DNA Methylation/genetics ; Enterobacteriaceae/*genetics/virology ; Genomics ; Interspersed Repetitive Sequences/*genetics ; *Phylogeny ; Symbiosis/genetics ; Wasps/pathogenicity ; }, abstract = {Many insects host facultative, bacterial symbionts that confer conditional fitness benefits to their hosts. Hamiltonella defensa is a common facultative symbiont of aphids that provides protection against parasitoid wasps. Protection levels vary among strains of H. defensa that are also differentially infected by bacteriophages named APSEs. However, little is known about trait variation among strains because only one isolate has been fully sequenced. Generating complete genomes for facultative symbionts is hindered by relatively large genome sizes but low abundances in hosts like aphids that are very small. Here, we took advantage of methods for culturing H. defensa outside of aphids to generate complete genomes and transcriptome data for four strains of H. defensa from the pea aphid Acyrthosiphon pisum. Chosen strains also spanned the breadth of the H. defensa phylogeny and differed in strength of protection conferred against parasitoids. Results indicated that strains shared most genes with roles in nutrient acquisition, metabolism, and essential housekeeping functions. In contrast, the inventory of mobile genetic elements varied substantially, which generated strain specific differences in gene content and genome architecture. In some cases, specific traits correlated with differences in protection against parasitoids, but in others high variation between strains obscured identification of traits with likely roles in defense. Transcriptome data generated continuous distributions to genome assemblies with some genes that were highly expressed and others that were not. Single molecule real-time sequencing further identified differences in DNA methylation patterns and restriction modification systems that provide defense against phage infection.}, } @article {pmid29452311, year = {2018}, author = {Walker, M and Lyra, ML and Haddad, CFB}, title = {Phylogenetic relationships and cryptic species diversity in the Brazilian egg-brooding tree frog, genus Fritziana Mello-Leitão 1937 (Anura: Hemiphractidae).}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {59-72}, doi = {10.1016/j.ympev.2018.02.012}, pmid = {29452311}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification/*genetics ; Bayes Theorem ; Brazil ; DNA, Mitochondrial/genetics ; Forests ; *Genetic Variation ; Geography ; *Phylogeny ; RNA, Transfer/genetics ; Species Specificity ; }, abstract = {The genus Fritziana (Anura: Hemiphractidae) comprises six described species (F. goeldii, F. ohausi, F. fissilis, F. ulei, F. tonimi, and F. izecksohni) that are endemic to the Brazilian Atlantic Forest. Although the genus has been the subject of studies dealing with its taxonomy, phylogeny, and systematics, there is considerable evidence for cryptic diversity hidden among the species. The present study aims to understand the genetic diversity and phylogenetic relationships among the species of Fritziana, as well as the relationships among populations within species. We analyzed 107 individuals throughout the distribution of the genus using three mitochondrial gene fragments (12S, 16S, and COI) and two nuclear genes (RAG1 and SLC8A3). Our data indicated that the species diversity in the genus Fritziana is underestimated by the existence of at least three candidate species hidden amongst the group of species with a closed dorsal pouch (i.e. F. fissilis and F. ulei). We also found four species presenting geographical population structures and high genetic diversity, and thus require further investigations. In addition, we found that two candidate species show a new arrangement for the tRNA-Phe gene, unique in Anura so far. Based on our results, we suggest that the conservation status of the species, as well as the species diversity in the genus Fritziana, needs to be reviewed.}, } @article {pmid29449511, year = {2018}, author = {Chen, JS and Ma, E and Harrington, LB and Da Costa, M and Tian, X and Palefsky, JM and Doudna, JA}, title = {CRISPR-Cas12a target binding unleashes indiscriminate single-stranded DNase activity.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {436-439}, doi = {10.1126/science.aar6245}, pmid = {29449511}, issn = {1095-9203}, mesh = {Bacterial Proteins/*chemistry ; CRISPR-Associated Proteins/*chemistry ; *CRISPR-Cas Systems ; Clostridiales/*enzymology ; *DNA Cleavage ; DNA, Single-Stranded/*chemistry ; Endonucleases/*chemistry ; Kinetics ; Substrate Specificity ; }, abstract = {CRISPR-Cas12a (Cpf1) proteins are RNA-guided enzymes that bind and cut DNA as components of bacterial adaptive immune systems. Like CRISPR-Cas9, Cas12a has been harnessed for genome editing on the basis of its ability to generate targeted, double-stranded DNA breaks. Here we show that RNA-guided DNA binding unleashes indiscriminate single-stranded DNA (ssDNA) cleavage activity by Cas12a that completely degrades ssDNA molecules. We find that target-activated, nonspecific single-stranded deoxyribonuclease (ssDNase) cleavage is also a property of other type V CRISPR-Cas12 enzymes. By combining Cas12a ssDNase activation with isothermal amplification, we create a method termed DNA endonuclease-targeted CRISPR trans reporter (DETECTR), which achieves attomolar sensitivity for DNA detection. DETECTR enables rapid and specific detection of human papillomavirus in patient samples, thereby providing a simple platform for molecular diagnostics.}, } @article {pmid29449510, year = {2018}, author = {Mills, LS and Bragina, EV and Kumar, AV and Zimova, M and Lafferty, DJR and Feltner, J and Davis, BM and Hackländer, K and Alves, PC and Good, JM and Melo-Ferreira, J and Dietz, A and Abramov, AV and Lopatina, N and Fay, K}, title = {Winter color polymorphisms identify global hot spots for evolutionary rescue from climate change.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1033-1036}, doi = {10.1126/science.aan8097}, pmid = {29449510}, issn = {1095-9203}, mesh = {Animals ; *Biodiversity ; *Biological Mimicry ; *Climate Change ; *Molting ; *Pigmentation ; Seasons ; Vertebrates ; }, abstract = {Maintenance of biodiversity in a rapidly changing climate will depend on the efficacy of evolutionary rescue, whereby population declines due to abrupt environmental change are reversed by shifts in genetically driven adaptive traits. However, a lack of traits known to be under direct selection by anthropogenic climate change has limited the incorporation of evolutionary processes into global conservation efforts. In 21 vertebrate species, some individuals undergo a seasonal color molt from summer brown to winter white as camouflage against snow, whereas other individuals remain brown. Seasonal snow duration is decreasing globally, and fitness is lower for winter white animals on snowless backgrounds. Based on 2713 georeferenced samples of known winter coat color-from eight species across trophic levels-we identify environmentally driven clinal gradients in winter coat color, including polymorphic zones where winter brown and white morphs co-occur. These polymorphic zones, underrepresented by existing global protected area networks, indicate hot spots for evolutionary rescue in a changing climate.}, } @article {pmid29449509, year = {2018}, author = {Ahneman, DT and Estrada, JG and Lin, S and Dreher, SD and Doyle, AG}, title = {Predicting reaction performance in C-N cross-coupling using machine learning.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {186-190}, doi = {10.1126/science.aar5169}, pmid = {29449509}, issn = {1095-9203}, abstract = {Machine learning methods are becoming integral to scientific inquiry in numerous disciplines. We demonstrated that machine learning can be used to predict the performance of a synthetic reaction in multidimensional chemical space using data obtained via high-throughput experimentation. We created scripts to compute and extract atomic, molecular, and vibrational descriptors for the components of a palladium-catalyzed Buchwald-Hartwig cross-coupling of aryl halides with 4-methylaniline in the presence of various potentially inhibitory additives. Using these descriptors as inputs and reaction yield as output, we showed that a random forest algorithm provides significantly improved predictive performance over linear regression analysis. The random forest model was also successfully applied to sparse training sets and out-of-sample prediction, suggesting its value in facilitating adoption of synthetic methodology.}, } @article {pmid29449508, year = {2018}, author = {Gootenberg, JS and Abudayyeh, OO and Kellner, MJ and Joung, J and Collins, JJ and Zhang, F}, title = {Multiplexed and portable nucleic acid detection platform with Cas13, Cas12a, and Csm6.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6387}, pages = {439-444}, pmid = {29449508}, issn = {1095-9203}, support = {R01 MH110049/MH/NIMH NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; DP1 HL141201/HL/NHLBI NIH HHS/United States ; R01 HG009761/HG/NHGRI NIH HHS/United States ; F30 CA210382/CA/NCI NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry ; CRISPR-Associated Proteins/*chemistry ; DNA/*analysis ; Dengue Virus/isolation & purification ; Endonucleases/*chemistry ; *Enzyme Assays ; Humans ; RNA/*analysis ; RNA, Viral/analysis ; Sensitivity and Specificity ; Zika Virus/isolation & purification ; }, abstract = {Rapid detection of nucleic acids is integral for clinical diagnostics and biotechnological applications. We recently developed a platform termed SHERLOCK (specific high-sensitivity enzymatic reporter unlocking) that combines isothermal preamplification with Cas13 to detect single molecules of RNA or DNA. Through characterization of CRISPR enzymology and application development, we report here four advances integrated into SHERLOCK version 2 (SHERLOCKv2) (i) four-channel single-reaction multiplexing with orthogonal CRISPR enzymes; (ii) quantitative measurement of input as low as 2 attomolar; (iii) 3.5-fold increase in signal sensitivity by combining Cas13 with Csm6, an auxiliary CRISPR-associated enzyme; and (iv) lateral-flow readout. SHERLOCKv2 can detect Dengue or Zika virus single-stranded RNA as well as mutations in patient liquid biopsy samples via lateral flow, highlighting its potential as a multiplexable, portable, rapid, and quantitative detection platform of nucleic acids.}, } @article {pmid29449507, year = {2018}, author = {Tang, W and Liu, DR}, title = {Rewritable multi-event analog recording in bacterial and mammalian cells.}, journal = {Science (New York, N.Y.)}, volume = {360}, number = {6385}, pages = {}, pmid = {29449507}, issn = {1095-9203}, support = {//Howard Hughes Medical Institute/United States ; R01 EB022376/EB/NIBIB NIH HHS/United States ; R35 GM118062/GM/NIGMS NIH HHS/United States ; RM1 HG009490/HG/NHGRI NIH HHS/United States ; }, mesh = {*Analog-Digital Conversion ; *Bacterial Proteins ; CRISPR-Associated Protein 9 ; *CRISPR-Cas Systems ; DNA, Bacterial/genetics/metabolism ; *Endonucleases ; Escherichia coli/genetics/metabolism/virology ; *Gene Editing ; HEK293 Cells ; Humans ; Plasmids/genetics/metabolism ; RNA, Guide/metabolism ; }, abstract = {We present two CRISPR-mediated analog multi-event recording apparatus (CAMERA) systems that use base editors and Cas9 nucleases to record cellular events in bacteria and mammalian cells. The devices record signal amplitude or duration as changes in the ratio of mutually exclusive DNA sequences (CAMERA 1) or as single-base modifications (CAMERA 2). We achieved recording of multiple stimuli in bacteria or mammalian cells, including exposure to antibiotics, nutrients, viruses, light, and changes in Wnt signaling. When recording to multicopy plasmids, reliable readout requires as few as 10 to 100 cells. The order of stimuli can be recorded through an overlapping guide RNA design, and memories can be erased and re-recorded over multiple cycles. CAMERA systems serve as "cell data recorders" that write a history of endogenous or exogenous signaling events into permanent DNA sequence modifications in living cells.}, } @article {pmid29449494, year = {2018}, author = {Calisi, RM}, title = {Got milk, must conference.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {838}, doi = {10.1126/science.359.6377.838}, pmid = {29449494}, issn = {1095-9203}, } @article {pmid29449493, year = {2018}, author = {Sherman, DJ and Xie, R and Taylor, RJ and George, AH and Okuda, S and Foster, PJ and Needleman, DJ and Kahne, D}, title = {Lipopolysaccharide is transported to the cell surface by a membrane-to-membrane protein bridge.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {798-801}, pmid = {29449493}, issn = {1095-9203}, support = {R01 AI081059/AI/NIAID NIH HHS/United States ; R01 GM066174/GM/NIGMS NIH HHS/United States ; U19 AI109764/AI/NIAID NIH HHS/United States ; }, mesh = {Biological Transport ; Carrier Proteins/*metabolism ; Cell Membrane/chemistry/*metabolism ; Escherichia coli/*metabolism ; Escherichia coli Proteins/*metabolism ; Lipopolysaccharides/*metabolism ; }, abstract = {Gram-negative bacteria have an outer membrane that serves as a barrier to noxious agents in the environment. This protective function is dependent on lipopolysaccharide, a large glycolipid located in the outer leaflet of the outer membrane. Lipopolysaccharide is synthesized at the cytoplasmic membrane and must be transported to the cell surface. To understand this transport process, we reconstituted membrane-to-membrane movement of lipopolysaccharide by incorporating purified inner and outer membrane transport complexes into separate proteoliposomes. Transport involved stable association between the inner and outer membrane proteoliposomes. Our results support a model in which lipopolysaccharide molecules are pushed one after the other in a PEZ dispenser-like manner across a protein bridge that connects the inner and outer membranes.}, } @article {pmid29449492, year = {2018}, author = {Ugurlar, D and Howes, SC and de Kreuk, BJ and Koning, RI and de Jong, RN and Beurskens, FJ and Schuurman, J and Koster, AJ and Sharp, TH and Parren, PWHI and Gros, P}, title = {Structures of C1-IgG1 provide insights into how danger pattern recognition activates complement.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {794-797}, doi = {10.1126/science.aao4988}, pmid = {29449492}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Alarmins/*chemistry/ultrastructure ; Antibodies, Monoclonal/chemistry/ultrastructure ; Binding Sites ; *Complement Activation ; Complement C1/*chemistry/ultrastructure ; Cryoelectron Microscopy ; Humans ; Immunoglobulin G/*chemistry/genetics/ultrastructure ; }, abstract = {Danger patterns on microbes or damaged host cells bind and activate C1, inducing innate immune responses and clearance through the complement cascade. How these patterns trigger complement initiation remains elusive. Here, we present cryo-electron microscopy analyses of C1 bound to monoclonal antibodies in which we observed heterogeneous structures of single and clustered C1-immunoglobulin G1 (IgG1) hexamer complexes. Distinct C1q binding sites are observed on the two Fc-CH2 domains of each IgG molecule. These are consistent with known interactions and also reveal additional interactions, which are supported by functional IgG1-mutant analysis. Upon antibody binding, the C1q arms condense, inducing rearrangements of the C1r2s2 proteases and tilting C1q's cone-shaped stalk. The data suggest that C1r may activate C1s within single, strained C1 complexes or between neighboring C1 complexes on surfaces.}, } @article {pmid29449491, year = {2018}, author = {Winfree, R and Reilly, JR and Bartomeus, I and Cariveau, DP and Williams, NM and Gibbs, J}, title = {Species turnover promotes the importance of bee diversity for crop pollination at regional scales.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {791-793}, doi = {10.1126/science.aao2117}, pmid = {29449491}, issn = {1095-9203}, mesh = {Animals ; *Bees ; *Biota ; *Crops, Agricultural ; *Pollination ; }, abstract = {Ecologists have shown through hundreds of experiments that ecological communities with more species produce higher levels of essential ecosystem functions such as biomass production, nutrient cycling, and pollination, but whether this finding holds in nature (that is, in large-scale and unmanipulated systems) is controversial. This knowledge gap is troubling because ecosystem services have been widely adopted as a justification for global biodiversity conservation. Here we show that, to provide crop pollination in natural systems, the number of bee species must increase by at least one order of magnitude compared with that in field experiments. This increase is driven by species turnover and its interaction with functional dominance, mechanisms that emerge only at large scales. Our results show that maintaining ecosystem services in nature requires many species, including relatively rare ones.}, } @article {pmid29449490, year = {2018}, author = {Bui, AD and Nguyen, TM and Limouse, C and Kim, HK and Szabo, GG and Felong, S and Maroso, M and Soltesz, I}, title = {Dentate gyrus mossy cells control spontaneous convulsive seizures and spatial memory.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {787-790}, pmid = {29449490}, issn = {1095-9203}, support = {F31 NS086429/NS/NINDS NIH HHS/United States ; P30 NS069375/NS/NINDS NIH HHS/United States ; R01 NS074702/NS/NINDS NIH HHS/United States ; R01 NS094668/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Disease Models, Animal ; Electroencephalography ; Epilepsy, Temporal Lobe/*physiopathology ; Female ; Male ; Mice ; Mice, Inbred C57BL ; Mossy Fibers, Hippocampal/*physiology/*physiopathology ; Neurons/physiology ; Optogenetics ; Seizures/*physiopathology ; Spatial Memory/*physiology ; }, abstract = {Temporal lobe epilepsy (TLE) is characterized by debilitating, recurring seizures and an increased risk for cognitive deficits. Mossy cells (MCs) are key neurons in the hippocampal excitatory circuit, and the partial loss of MCs is a major hallmark of TLE. We investigated how MCs contribute to spontaneous ictal activity and to spatial contextual memory in a mouse model of TLE with hippocampal sclerosis, using a combination of optogenetic, electrophysiological, and behavioral approaches. In chronically epileptic mice, real-time optogenetic modulation of MCs during spontaneous hippocampal seizures controlled the progression of activity from an electrographic to convulsive seizure. Decreased MC activity is sufficient to impede encoding of spatial context, recapitulating observed cognitive deficits in chronically epileptic mice.}, } @article {pmid29449489, year = {2018}, author = {Liang, QY and Venkatramani, AV and Cantu, SH and Nicholson, TL and Gullans, MJ and Gorshkov, AV and Thompson, JD and Chin, C and Lukin, MD and Vuletić, V}, title = {Observation of three-photon bound states in a quantum nonlinear medium.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {783-786}, doi = {10.1126/science.aao7293}, pmid = {29449489}, issn = {1095-9203}, abstract = {Bound states of massive particles, such as nuclei, atoms, or molecules, constitute the bulk of the visible world around us. By contrast, photons typically only interact weakly. We report the observation of traveling three-photon bound states in a quantum nonlinear medium where the interactions between photons are mediated by atomic Rydberg states. Photon correlation and conditional phase measurements reveal the distinct bunching and phase features associated with three-photon and two-photon bound states. Such photonic trimers and dimers possess shape-preserving wave functions that depend on the constituent photon number. The observed bunching and strongly nonlinear optical phase are described by an effective field theory of Rydberg-induced photon-photon interactions. These observations demonstrate the ability to realize and control strongly interacting quantum many-body states of light.}, } @article {pmid29449488, year = {2018}, author = {Morinaka, BI and Lakis, E and Verest, M and Helf, MJ and Scalvenzi, T and Vagstad, AL and Sims, J and Sunagawa, S and Gugger, M and Piel, J}, title = {Natural noncanonical protein splicing yields products with diverse β-amino acid residues.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {779-782}, doi = {10.1126/science.aao0157}, pmid = {29449488}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Amides/chemistry ; Amino Acid Sequence ; Amino Acids/chemistry/*metabolism ; Bacterial Proteins/genetics/*metabolism ; Cyanobacteria/genetics/*metabolism ; Escherichia coli/genetics ; Genetic Loci ; Mutation ; *Protein Processing, Post-Translational ; *Protein Splicing ; Tyramine/chemistry ; }, abstract = {Current textbook knowledge holds that the structural scope of ribosomal biosynthesis is based exclusively on α-amino acid backbone topology. Here we report the genome-guided discovery of bacterial pathways that posttranslationally create β-amino acid-containing products. The transformation is widespread in bacteria and is catalyzed by an enzyme belonging to a previously uncharacterized radical S-adenosylmethionine family. We show that the β-amino acids result from an unusual protein splicing process involving backbone carbon-carbon bond cleavage and net excision of tyramine. The reaction can be used to incorporate diverse and multiple β-amino acids into genetically encoded precursors in Escherichia coli In addition to enlarging the set of basic amino acid components, the excision generates keto functions that are useful as orthogonal reaction sites for chemical diversification.}, } @article {pmid29449487, year = {2018}, author = {Kumar, D and Paulsen, JD and Russell, TP and Menon, N}, title = {Wrapping with a splash: High-speed encapsulation with ultrathin sheets.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {775-778}, doi = {10.1126/science.aao1290}, pmid = {29449487}, issn = {1095-9203}, abstract = {Many complex fluids rely on surfactants to contain, protect, or isolate liquid drops in an immiscible continuous phase. Thin elastic sheets can wrap liquid drops in a spontaneous process driven by capillary forces. For encapsulation by sheets to be practically viable, a rapid, continuous, and scalable process is essential. We exploit the fast dynamics of droplet impact to achieve wrapping of oil droplets by ultrathin polymer films in a water phase. Despite the violence of splashing events, the process robustly yields wrappings that are optimally shaped to maximize the enclosed fluid volume and have near-perfect seams. We achieve wrappings of targeted three-dimensional (3D) shapes by tailoring the 2D boundary of the films and show the generality of the technique by producing both oil-in-water and water-in-oil wrappings.}, } @article {pmid29449486, year = {2018}, author = {Nosil, P and Villoutreix, R and de Carvalho, CF and Farkas, TE and Soria-Carrasco, V and Feder, JL and Crespi, BJ and Gompert, Z}, title = {Natural selection and the predictability of evolution in Timema stick insects.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {765-770}, doi = {10.1126/science.aap9125}, pmid = {29449486}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Animals ; *Biological Evolution ; Climate ; Environment ; Neoptera/*genetics ; Quantitative Trait, Heritable ; *Selection, Genetic ; }, abstract = {Predicting evolution remains difficult. We studied the evolution of cryptic body coloration and pattern in a stick insect using 25 years of field data, experiments, and genomics. We found that evolution is more difficult to predict when it involves a balance between multiple selective factors and uncertainty in environmental conditions than when it involves feedback loops that cause consistent back-and-forth fluctuations. Specifically, changes in color-morph frequencies are modestly predictable through time (r2 = 0.14) and driven by complex selective regimes and yearly fluctuations in climate. In contrast, temporal changes in pattern-morph frequencies are highly predictable due to negative frequency-dependent selection (r2 = 0.86). For both traits, however, natural selection drives evolution around a dynamic equilibrium, providing some predictability to the process.}, } @article {pmid29449485, year = {2018}, author = {McDonald, BC and de Gouw, JA and Gilman, JB and Jathar, SH and Akherati, A and Cappa, CD and Jimenez, JL and Lee-Taylor, J and Hayes, PL and McKeen, SA and Cui, YY and Kim, SW and Gentner, DR and Isaacman-VanWertz, G and Goldstein, AH and Harley, RA and Frost, GJ and Roberts, JM and Ryerson, TB and Trainer, M}, title = {Volatile chemical products emerging as largest petrochemical source of urban organic emissions.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {760-764}, doi = {10.1126/science.aaq0524}, pmid = {29449485}, issn = {1095-9203}, mesh = {Air Pollutants/*adverse effects/analysis ; Dioctyl Sulfosuccinic Acid ; *Environmental Exposure ; Humans ; Hydrocarbons/*adverse effects/analysis ; United States ; Volatile Organic Compounds/*adverse effects/analysis ; }, abstract = {A gap in emission inventories of urban volatile organic compound (VOC) sources, which contribute to regional ozone and aerosol burdens, has increased as transportation emissions in the United States and Europe have declined rapidly. A detailed mass balance demonstrates that the use of volatile chemical products (VCPs)-including pesticides, coatings, printing inks, adhesives, cleaning agents, and personal care products-now constitutes half of fossil fuel VOC emissions in industrialized cities. The high fraction of VCP emissions is consistent with observed urban outdoor and indoor air measurements. We show that human exposure to carbonaceous aerosols of fossil origin is transitioning away from transportation-related sources and toward VCPs. Existing U.S. regulations on VCPs emphasize mitigating ozone and air toxics, but they currently exempt many chemicals that lead to secondary organic aerosols.}, } @article {pmid29449484, year = {2018}, author = {}, title = {As autonomous vehicles approach.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {755}, doi = {10.1126/science.aat1490}, pmid = {29449484}, issn = {1095-9203}, } @article {pmid29449483, year = {2018}, author = {Sikes, RS and Kelt, DA and Beissinger, SR and Martin, K and Crother, BI and Cole, KS}, title = {Fund the Biological Survey Unit.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {754-755}, doi = {10.1126/science.aas9289}, pmid = {29449483}, issn = {1095-9203}, mesh = {*Biota ; Budgets ; Environmental Monitoring/*economics ; Maryland ; }, } @article {pmid29449482, year = {2018}, author = {Bradley, TJ and Yanega, GM}, title = {Salton Sea: Ecosystem in transition.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {754}, doi = {10.1126/science.aar6088}, pmid = {29449482}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; *Birds ; California ; *Conservation of Water Resources ; Ecosystem ; Fishes ; *Lakes ; }, } @article {pmid29449481, year = {2018}, author = {Johns, DM and Oppenheimer, GM}, title = {Was there ever really a "sugar conspiracy"?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {747-750}, doi = {10.1126/science.aaq1618}, pmid = {29449481}, issn = {1095-9203}, mesh = {Heart Diseases/epidemiology ; History, 20th Century ; Humans ; Nutritional Sciences/*history ; Obesity/epidemiology ; Policy ; Sugars/adverse effects/*history ; }, } @article {pmid29449480, year = {2018}, author = {Ghorani, E and Quezada, SA}, title = {Chromatin regulation and immune escape.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {745-746}, doi = {10.1126/science.aat0383}, pmid = {29449480}, issn = {1095-9203}, mesh = {*Chromatin ; Humans ; Tumor Escape/*immunology ; }, } @article {pmid29449479, year = {2018}, author = {Lewis, AC}, title = {The changing face of urban air pollution.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {744-745}, doi = {10.1126/science.aar4925}, pmid = {29449479}, issn = {1095-9203}, mesh = {Air Pollutants/*analysis ; Air Pollution/*analysis ; Humans ; Urban Health ; Urban Population ; }, } @article {pmid29449478, year = {2018}, author = {Amstad, E}, title = {Capsules made from prefabricated thin films.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {743}, doi = {10.1126/science.aar4027}, pmid = {29449478}, issn = {1095-9203}, mesh = {*Capsules ; }, } @article {pmid29449477, year = {2018}, author = {Kremen, C}, title = {The value of pollinator species diversity.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {741-742}, doi = {10.1126/science.aar7614}, pmid = {29449477}, issn = {1095-9203}, mesh = {*Biodiversity ; Flowers ; Insecta ; *Pollination ; Species Specificity ; }, } @article {pmid29449476, year = {2018}, author = {Scharfman, HE}, title = {Controlling learning and epilepsy together.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {740-741}, pmid = {29449476}, issn = {1095-9203}, support = {R01 MH109305/MH/NIMH NIH HHS/United States ; }, mesh = {*Epilepsy ; Humans ; *Learning ; Learning Disorders ; }, } @article {pmid29449475, year = {2018}, author = {Reznick, D and Travis, J}, title = {Is evolution predictable?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {738-739}, doi = {10.1126/science.aas9043}, pmid = {29449475}, issn = {1095-9203}, mesh = {*Biological Evolution ; *Evolution, Molecular ; }, } @article {pmid29449474, year = {2018}, author = {Rosen, J}, title = {The carbon harvest.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {733-737}, doi = {10.1126/science.359.6377.733}, pmid = {29449474}, issn = {1095-9203}, } @article {pmid29449473, year = {2018}, author = {Marcus, A and Oransky, I}, title = {The data thugs.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {730-732}, doi = {10.1126/science.359.6377.730}, pmid = {29449473}, issn = {1095-9203}, } @article {pmid29449472, year = {2018}, author = {Cartlidge, E}, title = {Isotope cloud linked to failed neutrino source.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {729}, doi = {10.1126/science.359.6377.729}, pmid = {29449472}, issn = {1095-9203}, } @article {pmid29449471, year = {2018}, author = {Cohen, J}, title = {'CAMERA' records cell action with new CRISPR tricks.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {728}, doi = {10.1126/science.359.6377.728}, pmid = {29449471}, issn = {1095-9203}, mesh = {*CRISPR-Cas Systems ; DNA Cleavage ; *Gene Editing ; Humans ; Molecular Imaging/*methods ; Plasmids ; Single-Cell Analysis/*methods ; Tape Recording/*methods ; }, } @article {pmid29449470, year = {2018}, author = {Rabesandratana, T}, title = {U.K. moms are turning parenting into an experiment.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {726-727}, doi = {10.1126/science.359.6377.726}, pmid = {29449470}, issn = {1095-9203}, mesh = {Body Temperature ; *Breast Feeding ; Breast Neoplasms/*epidemiology ; Female ; Humans ; Lactation ; *Milk, Human ; *Mothers ; *Parenting ; Schools ; Tissue Donors ; United Kingdom ; }, } @article {pmid29449469, year = {2018}, author = {Hutson, M}, title = {Artificial intelligence faces reproducibility crisis.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {725-726}, doi = {10.1126/science.359.6377.725}, pmid = {29449469}, issn = {1095-9203}, mesh = {*Artificial Intelligence ; Reproducibility of Results ; }, } @article {pmid29449468, year = {2018}, author = {Cho, A}, title = {A weight limit emerges for neutron stars.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {724-725}, doi = {10.1126/science.359.6377.724}, pmid = {29449468}, issn = {1095-9203}, } @article {pmid29449467, year = {2018}, author = {, }, title = {Science gets modest reprieve in Trump budget.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {723-724}, doi = {10.1126/science.359.6377.723}, pmid = {29449467}, issn = {1095-9203}, } @article {pmid29449466, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {720-722}, doi = {10.1126/science.359.6377.720}, pmid = {29449466}, issn = {1095-9203}, } @article {pmid29449465, year = {2018}, author = {Cordes, EE and Levin, LA}, title = {Exploration before exploitation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {719}, doi = {10.1126/science.aat2637}, pmid = {29449465}, issn = {1095-9203}, mesh = {Animals ; *Aquatic Organisms ; Oceans and Seas ; Oil and Gas Industry/*legislation & jurisprudence ; Petroleum Pollution/*legislation & jurisprudence ; }, } @article {pmid29449464, year = {2018}, author = {Sushkevich, VL and Palagin, D and Ranocchiari, M and van Bokhoven, JA}, title = {Response to Comment on "Selective anaerobic oxidation of methane enables direct synthesis of methanol".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {}, doi = {10.1126/science.aar6868}, pmid = {29449464}, issn = {1095-9203}, mesh = {Methane/*chemistry ; Methanol/*chemical synthesis ; Oxidation-Reduction ; Temperature ; Thermodynamics ; }, abstract = {Labinger argues that stepwise reaction of methane with water to produce methanol and hydrogen will never be commercially feasible because of its substoichiometric basis with respect to the active site and the requirement of a large temperature swing. This comment is not touching any new ground, beyond describing the thermodynamic feasibility, thermal cycling, and the role of water as discussed previously. Most important, it does not have a solid numerical basis.}, } @article {pmid29449463, year = {2018}, author = {Labinger, JA}, title = {Comment on "Selective anaerobic oxidation of methane enables direct synthesis of methanol".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {}, doi = {10.1126/science.aar4968}, pmid = {29449463}, issn = {1095-9203}, abstract = {The comment and response concerning the report of oxidation of methane to methanol by water (Reports, 5 May 2017, p. 523) do not fully capture the implications of thermodynamic limitations. A nonisothermal process in which each cycle requires a large temperature swing and permits only substoichiometric methane conversion surely could not be carried out on any practical scale.}, } @article {pmid29449462, year = {2018}, author = {Saint-Denis, TG and Zhu, RY and Chen, G and Wu, QF and Yu, JQ}, title = {Enantioselective C(sp3)‒H bond activation by chiral transition metal catalysts.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {}, pmid = {29449462}, issn = {1095-9203}, support = {R01 GM084019/GM/NIGMS NIH HHS/United States ; }, abstract = {Organic molecules are rich in carbon-hydrogen bonds; consequently, the transformation of C-H bonds to new functionalities (such as C-C, C-N, and C-O bonds) has garnered much attention by the synthetic chemistry community. The utility of C-H activation in organic synthesis, however, cannot be fully realized until chemists achieve stereocontrol in the modification of C-H bonds. This Review highlights recent efforts to enantioselectively functionalize C(sp3)-H bonds via transition metal catalysis, with an emphasis on key principles for both the development of chiral ligand scaffolds that can accelerate metalation of C(sp3)-H bonds and stereomodels for asymmetric metalation of prochiral C-H bonds by these catalysts.}, } @article {pmid29449350, year = {2018}, author = {Goldfarb, B and King, AA and Simcoe, TS}, title = {Heritability of trust and distrust remains unknown.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2149-E2150}, pmid = {29449350}, issn = {1091-6490}, mesh = {*Interpersonal Relations ; *Trust ; }, } @article {pmid29449349, year = {2018}, author = {Reimann, M and Schilke, O and Estabrook, R and Cook, KS}, title = {Reply to Goldfarb et al.: On the heritability and socialization of trust and distrust.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2151-E2152}, pmid = {29449349}, issn = {1091-6490}, mesh = {Humans ; Interpersonal Relations ; *Socialization ; *Trust ; *Wills ; }, } @article {pmid29449348, year = {2018}, author = {Vergassola, M and Deneke, VE and Di Talia, S}, title = {Mitotic waves in the early embryogenesis of Drosophila: Bistability traded for speed.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2165-E2174}, pmid = {29449348}, issn = {1091-6490}, support = {R00 HD074670/HD/NICHD NIH HHS/United States ; R01 GM122936/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; CDC2 Protein Kinase/analysis/genetics/metabolism ; *Cell Cycle/genetics/physiology ; Drosophila/*embryology/genetics/physiology ; Embryo, Nonmammalian ; *Embryonic Development/genetics/physiology ; *Models, Biological ; Time Factors ; Zygote/growth & development ; }, abstract = {Early embryogenesis of most metazoans is characterized by rapid and synchronous cleavage divisions. Chemical waves of Cdk1 activity were previously shown to spread across Drosophila embryos, and the underlying molecular processes were dissected. Here, we present the theory of the physical mechanisms that control Cdk1 waves in Drosophila The in vivo dynamics of Cdk1 are captured by a transiently bistable reaction-diffusion model, where time-dependent reaction terms account for the growing level of cyclins and Cdk1 activation across the cell cycle. We identify two distinct regimes. The first one is observed in mutants of the mitotic switch. There, waves are triggered by the classical mechanism of a stable state invading a metastable one. Conversely, waves in wild type reflect a transient phase that preserves the Cdk1 spatial gradients while the overall level of Cdk1 activity is swept upward by the time-dependent reaction terms. This unique mechanism generates a wave-like spreading that differs from bistable waves for its dependence on dynamic parameters and its faster speed. Namely, the speed of "sweep" waves strikingly decreases as the strength of the reaction terms increases and scales as the powers 3/4, -1/2, and 7/12 of Cdk1 molecular diffusivity, noise amplitude, and rate of increase of Cdk1 activity in the cell-cycle S phase, respectively. Theoretical predictions are supported by numerical simulations and experiments that couple quantitative measurements of Cdk1 activity and genetic perturbations of the accumulation rate of cyclins. Finally, our analysis bears upon the inhibition required to suppress Cdk1 waves at the cell-cycle pause for the maternal-to-zygotic transition.}, } @article {pmid29448969, year = {2018}, author = {Walle, B and Lebeta, KR and Fita, YD and Abdissa, HG}, title = {Prevalence of erectile dysfunction and associated factors among diabetic men attending the diabetic clinic at Felege Hiwot Referral Hospital, Bahir Dar, North West Ethiopia, 2016.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {130}, pmid = {29448969}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Age Factors ; Cross-Sectional Studies ; Diabetes Complications/*epidemiology ; Erectile Dysfunction/*epidemiology ; Ethiopia/epidemiology ; Humans ; Male ; Middle Aged ; Prevalence ; Young Adult ; }, abstract = {OBJECTIVE: Even though several scholars have conducted study in different part of the world on erectile dysfunction in patients diagnosed with diabetes mellitus, it's magnitude vary among their finding with the range between 20 and 90%. This study aimed at assessing the prevalence of erectile dysfunction and associated factors among diabetic clients.

RESULTS: A cross sectional study was conducted from January 2016 to March, 2016. Systematic random sampling technique was used. Data were collected using a structured questionnaire and level of erectile dysfunction was measured using the international index of erectile function. A total of 422 diabetic patients were participated with 100% response rate. The proportion of erectile dysfunction was 85.5% and it was significantly associated with higher age (AOR: 6.46, 95% CI 2.55-16.44) and Diabetic complication (AOR: 3.97, 95% CI 1.06-17.36). Therefore, screening for ED in diabetic patients, particularly for those who are in advanced age and living with DM for more than 10 years is needed for it's early detection, prevention and management.}, } @article {pmid29448952, year = {2018}, author = {Kasai, Y and Mizuno, T and Sakakibara, T and Thu, S and Kyaw, TA and Htun, KA}, title = {A survey of workplace violence against physicians in the hospitals, Myanmar.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {133}, pmid = {29448952}, issn = {1756-0500}, mesh = {Adult ; Female ; Health Care Surveys/statistics & numerical data ; Hospitals/*statistics & numerical data ; Humans ; Male ; Middle Aged ; Myanmar/epidemiology ; Physicians/*statistics & numerical data ; Workplace Violence/*statistics & numerical data ; }, abstract = {OBJECTIVE: Workplace violence in hospitals is recently becoming a major global concern in many countries. However, in Myanmar, we have felt that patients and their families have rarely made unreasonable complaints in hospitals, and then, the purpose of this study is to report the current state of workplace violence in hospitals in Myanmar. Participants are 196 physicians (108 males and 88 females) in hospitals in Myanmar.

RESULTS: A descriptive survey was conducted in regard to verbal abuse and physical violence from patients or the people concerned. At the results of this study, the percentages of physicians who have encountered verbal abuse and those who have encountered physical violence are markedly low (8.7 and 1.0%, respectively). The present study is the first to report the frequencies of verbal abuse and physical violence against physicians in a least developed country, and the results of the present study are important in terms of discussing workplace violence in hospitals.}, } @article {pmid29448951, year = {2018}, author = {Alyethodi, RR and Singh, U and Kumar, S and Alex, R and Deb, R and Sengar, GS and Raja, TV and Prakash, B}, title = {T-ARMS PCR genotyping of SNP rs445709131 using thermostable strand displacement polymerase.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {132}, pmid = {29448951}, issn = {1756-0500}, mesh = {Animals ; Cattle ; Cattle Diseases/*genetics ; Genotyping Techniques/*methods/standards ; Leukocyte-Adhesion Deficiency Syndrome/*genetics ; Polymerase Chain Reaction/*methods/standards ; Polymorphism, Single Nucleotide ; *Taq Polymerase ; }, abstract = {OBJECTIVES: In a recent publication, we reported the successful use of tetra primer-amplification refractory mutation system based polymerase chain reaction (T-ARMS-PCR) for genotyping of rs445709131-SNP responsible for the bovine leukocyte adhesion deficiency (BLAD) in cattle. The SNP is characterized by higher GC content of the surrounding region, hence, the previous protocol utilized dimethyl sulfoxide as PCR enhancer. Here, the reaction cocktail was modified with the use of thermostable strand displacement polymerase (SD polymerase) instead of commonly used Taq DNA Polymerase. The amplification efficiency, reaction sensitivity, specificity, and need of PCR enhancer in reactions containing SD polymerase and Taq polymerase were compared.

RESULTS: T-ARMS-PCR assay is influenced by multiple factors for the correct genotyping necessitating extensive optimization at the initial stages. The described modification enabled generation of all amplicons by 25 cycles whereas the assay with Taq polymerase needed a minimum of 35 cycles. The modified assay amplified all amplicons at a wider range of annealing temperature (50-60 °C), without the addition of dimethyl sulfoxide. The replacement of Taq polymerase with SD polymerase may be beneficial in the T-ARMS assay for development of user-friendly, faster assay which is less affected by the reaction and cyclic conditions.}, } @article {pmid29448948, year = {2018}, author = {Ismail, S and Awan, S and Naeem, R and Siddiqui, S and Afzal, B and Jamil, B and Khan, UR}, title = {Occupational exposure to HIV in a developing country: assessing knowledge and attitude of healthcare professional before and after an awareness symposium.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {131}, pmid = {29448948}, issn = {1756-0500}, support = {(3D43TW007292-09S1)//Johns Hopkins-Pakistan International Collaborative Trauma and Injury Research Training Program/ ; }, mesh = {Adolescent ; Adult ; *Attitude of Health Personnel ; *Education, Medical, Continuing ; Female ; *HIV Infections/prevention & control ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; *Occupational Exposure/prevention & control ; Pakistan ; Young Adult ; }, abstract = {OBJECTIVE: Health care providers (HCPs) are at risk of occupational exposure to HIV infection. In developing world these exposure occur due to general lack of awareness, education and structured training of HCPs. The objective of the study was to asses if continuing medical education symposium can be used as an effective educational tool to improve attitude, awareness and knowledge regarding occupational exposure to HIV infection. This quasi-experimental study was conducted among HCPs from Karachi, Pakistan. After assessing the baseline knowledge, awareness, and attitude by means of pretest; HCPs were reassessed with posttest after an education symposium on occupational exposure to HIV infection.

RESULTS: Among 364 participating HCPs, 14.2% had previous training on post exposure prophylaxis. There was an overall statistically significant (P value < 0.001) improvement in the attitude of the participants. A statistically positive improvement in the number of participants giving correct answer was observed in 9 out of 11 questions (P value < 0.001). The mean score of participants' knowledge before intervention was 6.44 ± 1.84, which improved to 8.82 ± 2.17. Along with the increase in knowledge, a positive change in the attitude regarding safety against HIV was observed after the education symposium.}, } @article {pmid29448946, year = {2018}, author = {Chang, LY and Toghiani, S and Ling, A and Aggrey, SE and Rekaya, R}, title = {Correction to: High density marker panels, SNPs prioritizing and accuracy of genomic selection.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {13}, pmid = {29448946}, issn = {1471-2156}, abstract = {CORRECTION TO: BMC GENETICS (2018) 19:4 DOI: 10.1186/S12863-017-0595-2: The original version of this article [1], published on 5 January 2018, contained 3 formatting errors. In this Correction the affected parts of the article are shown. The original article has been updated.}, } @article {pmid29448945, year = {2018}, author = {Kaushik, K and Sivadas, A and Vellarikkal, SK and Verma, A and Jayarajan, R and Pandey, S and Sethi, T and Maiti, S and Scaria, V and Sivasubbu, S}, title = {RNA secondary structure profiling in zebrafish reveals unique regulatory features.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {147}, pmid = {29448945}, issn = {1471-2164}, support = {BSC0123//Council of Scientific and Industrial Research/International ; IA/CPHE/14/1/501504//Wellcome Trust-DBT India Alliance/India ; }, mesh = {3' Untranslated Regions/genetics ; 5' Untranslated Regions/genetics ; Animals ; Base Sequence ; Codon, Initiator/genetics ; Codon, Terminator/genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Nucleic Acid Conformation ; Protein Biosynthesis ; RNA/chemistry/*genetics ; RNA, Messenger/chemistry/genetics ; Sequence Homology, Nucleic Acid ; Zebrafish/*genetics ; }, abstract = {BACKGROUND: RNA is known to play diverse roles in gene regulation. The clues for this regulatory function of RNA are embedded in its ability to fold into intricate secondary and tertiary structure.

RESULTS: We report the transcriptome-wide RNA secondary structure in zebrafish at single nucleotide resolution using Parallel Analysis of RNA Structure (PARS). This study provides the secondary structure map of zebrafish coding and non-coding RNAs. The single nucleotide pairing probabilities of 54,083 distinct transcripts in the zebrafish genome were documented. We identified RNA secondary structural features embedded in functional units of zebrafish mRNAs. Translation start and stop sites were demarcated by weak structural signals. The coding regions were characterized by the three-nucleotide periodicity of secondary structure and display a codon base specific structural constrain. The splice sites of transcripts were also delineated by distinct signature signals. Relatively higher structural signals were observed at 3' Untranslated Regions (UTRs) compared to Coding DNA Sequence (CDS) and 5' UTRs. The 3' ends of transcripts were also marked by unique structure signals. Secondary structural signals in long non-coding RNAs were also explored to better understand their molecular function.

CONCLUSIONS: Our study presents the first PARS-enabled transcriptome-wide secondary structure map of zebrafish, which documents pairing probability of RNA at single nucleotide precision. Our findings open avenues for exploring structural features in zebrafish RNAs and their influence on gene expression.}, } @article {pmid29448940, year = {2018}, author = {Lei, Y and Xu, Y and Hettenhausen, C and Lu, C and Shen, G and Zhang, C and Li, J and Song, J and Lin, H and Wu, J}, title = {Comparative analysis of alfalfa (Medicago sativa L.) leaf transcriptomes reveals genotype-specific salt tolerance mechanisms.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {35}, pmid = {29448940}, issn = {1471-2229}, support = {XDB11050200//the Strategic Priority Research Program of the Chinese Academy of Sciences (CAS)/ ; 2014FB171//the general Project of Applied Basic Research Program of Yunnan/ ; }, mesh = {Abscisic Acid ; Gene Expression Regulation, Plant/drug effects/genetics ; Genotype ; Medicago sativa/*drug effects/*genetics ; Plant Leaves/*drug effects/*genetics ; Salt Tolerance/genetics/physiology ; Sodium Chloride/pharmacology ; Transcriptome/*genetics ; }, abstract = {BACKGROUND: Soil salinity is an important factor affecting growth, development, and productivity of almost all land plants, including the forage crop alfalfa (Medicago sativa). However, little is known about how alfalfa responds and adapts to salt stress, particularly among different salt-tolerant cultivars.

RESULTS: Among seven alfalfa cultivars, we found that Zhongmu-1 (ZM) is relatively salt-tolerant and Xingjiang Daye (XJ) is salt-sensitive. Compared to XJ, ZM showed slower growth under low-salt conditions, but exhibited stronger tolerance to salt stress. RNA-seq analysis revealed 2237 and 1125 differentially expressed genes (DEGs) between ZM and XJ in the presence and absence of salt stress, among which many genes are involved in stress-related pathways. After salt treatment, compared with the controls, the number of DEGs in XJ (19373) was about four times of that in ZM (4833). We also detected specific differential gene expression patterns: In response to salt stress, compared with XJ, ZM maintained relatively more stable expression levels of genes related to the ROS and Ca2+ pathways, phytohormone biosynthesis, and Na+/K+ transport. Notably, several salt resistance-associated genes always showed greater levels of expression in ZM than in XJ, including a transcription factor. Consistent with the suppression of plant growth resulting from salt stress, the expression of numerous photosynthesis- and growth hormone-related genes decreased more dramatically in XJ than in ZM. By contrast, the expression levels of photosynthetic genes were lower in ZM under low-salt conditions.

CONCLUSIONS: Compared with XJ, ZM is a salt-tolerant alfalfa cultivar possessing specific regulatory mechanisms conferring exceptional salt tolerance, likely by maintaining high transcript levels of abiotic and biotic stress resistance-related genes. Our results suggest that maintaining this specific physiological status and/or plant adaptation to salt stress most likely arises by inhibition of plant growth in ZM through plant hormone interactions. This study identifies new candidate genes that may regulate alfalfa tolerance to salt stress and increases the understanding of the genetic basis for salt tolerance.}, } @article {pmid29448932, year = {2018}, author = {Cannicci, S and Fusi, M and Cimó, F and Dahdouh-Guebas, F and Fratini, S}, title = {Interference competition as a key determinant for spatial distribution of mangrove crabs.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {8}, pmid = {29448932}, issn = {1472-6785}, support = {RBAU01H5C3_001//Ministero dell'Istruzione, dell'Università e della Ricerca/International ; }, abstract = {BACKGROUND: The spatial distribution of mangrove crabs has been commonly associated with tree zonation and abiotic factors such as ground temperature and soil granulometry. Conversely, no studies were designed to investigate the role of competition for resources and predation in shaping crab distribution in mangroves, despite these biotic factors are recognised as key determinants for spatial patterns observed in the communities colonising rocky and sandy intertidal habitats.We studied floral and faunal assemblages in two zones of a Sri Lankan mangrove, a man-made upper intertidal level and a natural eulittoral, mid-shore one. Leaf choice experiments were designed to study both feeding rate and intra and inter-specific interactions for food of sesarmid crabs in the two habitats in order to better understand crab spatial distribution.

RESULTS: The two intertidal belts differed in terms of floral composition and crab species abundance. The eulittoral zone was strongly dominated by Neosarmatium smithi, while within the elevated littoral fringe four sesarmids (N. smithi, N. asiaticum, N. malabaricum and Muradium tetragonum) were more evenly distributed. At both levels, all sesarmids showed to collect significantly more Bruguiera spp. and Rhizophora apiculata leaves than Excoecaria agallocha ones. There was no temporal segregation in feeding activity among the four species, resulting in a high interference competition for leaves. Regardless of the habitat, N. smithi was always successful in winning inter-specific fights.

CONCLUSIONS: Our results showed that the elevated littoral fringe was more crowded with crabs, but was less favourable in terms of food availability and environmental conditions. The dominance of N. smithi in gathering mangrove leaves suggests that this species may segregate the other sesarmids into less favourable habitats. The present data strongly suggest for the first time that interference competition for food can contribute to shape mangrove crab spatial distribution.}, } @article {pmid29448924, year = {2018}, author = {Liu, T and Hu, X and Zhang, J and Zhang, J and Du, Q and Li, J}, title = {H2O2 mediates ALA-induced glutathione and ascorbate accumulation in the perception and resistance to oxidative stress in Solanum lycopersicum at low temperatures.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {34}, pmid = {29448924}, issn = {1471-2229}, support = {2013AA103004//The National High-tech R&D Program of China (863 Program)/ ; CARS-23-C-05//The China Agriculture Research System/ ; }, mesh = {Aminolevulinic Acid/*pharmacology ; Ascorbic Acid/*metabolism ; Cold Temperature ; Glutathione/*metabolism ; Hydrogen Peroxide/*pharmacology ; Lycopersicon esculentum/drug effects/*metabolism ; Oxidation-Reduction/drug effects ; Oxidative Stress/drug effects ; Temperature ; }, abstract = {BACKGROUND: Low temperature is a crucial factor influencing plant growth and development. The chlorophyll precursor, 5-aminolevulinic acid (ALA) is widely used to improve plant cold tolerance. However, the interaction between H2O2 and cellular redox signaling involved in ALA-induced resistance to low temperature stress in plants remains largely unknown. Here, the roles of ALA in perceiving and regulating low temperature-induced oxidative stress in tomato plants, together with the roles of H2O2 and cellular redox states, were characterized.

RESULTS: Low concentrations (10-25 mg·L- 1) of ALA enhanced low temperature-induced oxidative stress tolerance of tomato seedlings. The most effective concentration was 25 mg·L- 1, which markedly increased the ratio of reduced glutathione and ascorbate (GSH and AsA), and enhanced the activities of superoxide dismutase, catalase, ascorbate peroxidase, dehydroascorbate reductase, and glutathione reductase. Furthermore, gene expression of respiratory burst oxidase homolog1 and H2O2 content were upregulated with ALA treatment under normal conditions. Treatment with exogenous H2O2, GSH, and AsA also induced plant tolerance to oxidative stress at low temperatures, while inhibition of GSH and AsA syntheses significantly decreased H2O2-induced oxidative stress tolerance. Meanwhile, scavenging or inhibition of H2O2 production weakened, but did not eliminate, GSH- or AsA- induced tomato plant tolerance to oxidative stress at low temperatures.

CONCLUSIONS: Appropriate concentrations of ALA alleviated the low temperature-induced oxidative stress in tomato plants via an antioxidant system. The most effective concentration was 25 mg·L- 1. The results showed that H2O2 induced by exogenous ALA under normal conditions is crucial and may be the initial step for perception and signaling transmission, which then improves the ratio of GSH and AsA. GSH and AsA may then interact with H2O2 signaling, resulting in enhanced antioxidant capacity in tomato plants at low temperatures.}, } @article {pmid29448923, year = {2018}, author = {Yang, LH and Han, BA}, title = {Data-driven predictions and novel hypotheses about zoonotic tick vectors from the genus Ixodes.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {7}, pmid = {29448923}, issn = {1472-6785}, support = {1717282//Directorate for Biological Sciences/International ; }, abstract = {BACKGROUND: With the resurgence of tick-borne diseases such as Lyme disease and the emergence of new tick-borne pathogens such as Powassan virus, understanding what distinguishes vectors from non-vectors, and predicting undiscovered tick vectors is a crucial step towards mitigating disease risk in humans. We aimed to identify intrinsic traits that predict which Ixodes tick species are confirmed or strongly suspected to be vectors of zoonotic pathogens.

METHODS: We focused on the well-studied tick genus Ixodes from which many species are known to transmit zoonotic diseases to humans. We apply generalized boosted regression to interrogate over 90 features for over 240 species of Ixodes ticks to learn what intrinsic features distinguish zoonotic vectors from non-vector species. In addition to better understanding the biological underpinnings of tick vectorial capacity, the model generates a per species probability of being a zoonotic vector on the basis of intrinsic biological similarity with known Ixodes vector species.

RESULTS: Our model predicted vector status with over 91% accuracy, and identified 14 Ixodes species with high probabilities (80%) of transmitting infections from animal hosts to humans on the basis of their traits. Distinguishing characteristics of zoonotic tick vectors of Ixodes tick species include several anatomical structures that influence host seeking behavior and blood-feeding efficiency from a greater diversity of host species compared to non-vectors.

CONCLUSIONS: Overall, these results suggest that zoonotic tick vectors are most likely to be those species where adult females hold a fecundity advantage by producing more eggs per clutch, which develop into larvae that feed on a greater diversity of host species compared to non-vector species. These larvae develop into nymphs whose anatomy are well suited for more efficient and longer feeding times on soft-bodied hosts compared to non-vectors, leading to larger adult females with greater fecundity. In addition to identifying novel, testable hypotheses about intrinsic features driving vectorial capacity across Ixodes tick species, our model identifies particular Ixodes species with the highest probability of carrying zoonotic diseases, offering specific targets for increased zoonotic investigation and surveillance.}, } @article {pmid29448174, year = {2018}, author = {Schatz, D and Vardi, A}, title = {Extracellular vesicles - new players in cell-cell communication in aquatic environments.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {148-154}, doi = {10.1016/j.mib.2018.01.014}, pmid = {29448174}, issn = {1879-0364}, mesh = {Animals ; Aquatic Organisms/*physiology ; Bacteria ; *Bacterial Physiological Phenomena ; Ecosystem ; Extracellular Vesicles/*physiology ; Host-Pathogen Interactions ; Marine Biology ; MicroRNAs/metabolism ; *Microbial Interactions ; Quorum Sensing ; Signal Transduction ; }, abstract = {Communication between microorganisms in aquatic environments can influence ecosystem function and determine the structure and composition of microbial populations. This microbial cross talk can be mediated by excretion of specialized metabolites or extracellular vesicles (EVs). Recently it has become apparent that cells across all domains of life produce EVs that may convey specific targeted signals that can modulate cell fate, morphology and susceptibility to viruses. The vast majority of knowledge about EVs is derived from studies of mammalian tissues, parasitic host-pathogen interactions and model bacterial systems. Very little is known about the role of EVs in aquatic environments, although they have potential to influence community structure and trophic-level interactions. We propose functions and ecological implications of communication via EVs in aquatic microbial ecosystems.}, } @article {pmid29448063, year = {2018}, author = {Matos-Maraví, P and Clouse, RM and Sarnat, EM and Economo, EP and LaPolla, JS and Borovanska, M and Rabeling, C and Czekanski-Moir, J and Latumahina, F and Wilson, EO and Janda, M}, title = {An ant genus-group (Prenolepis) illuminates the biogeography and drivers of insect diversification in the Indo-Pacific.}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {16-25}, doi = {10.1016/j.ympev.2018.02.007}, pmid = {29448063}, issn = {1095-9513}, mesh = {Animals ; Ants ; Asia ; Australia ; *Biodiversity ; Calibration ; Fossils ; Geography ; Indonesia ; New Guinea ; Phylogeny ; *Phylogeography ; Species Specificity ; Time Factors ; }, abstract = {The Malay Archipelago and the tropical South Pacific (hereafter the Indo-Pacific region) are considered biodiversity hotspots, yet a general understanding of the origins and diversification of species-rich groups in the region remains elusive. We aimed to test hypotheses for the evolutionary processes driving insect species diversity in the Indo-Pacific using a higher-level and comprehensive phylogenetic hypothesis for an ant clade consisting of seven genera. We estimated divergence times and reconstructed the biogeographical history of ant species in the Prenolepis genus-group (Formicidae: Formicinae: Lasiini). We used a fossil-calibrated phylogeny to infer ancestral geographical ranges utilizing a biogeographic model that includes founder-event speciation. Ancestral state reconstructions of the ants' ecological preferences, and diversification rates were estimated for selected Indo-Pacific clades. Overall, we report that faunal interchange between Asia and Australia has occurred since at least 20-25 Ma, and early dispersal to the Fijian Basin happened during the early and mid-Miocene (ca. 10-20 Ma). Differences in diversification rates across Indo-Pacific clades may be related to ecological preference breadth, which in turn may have facilitated geographical range expansions. Ancient dispersal routes suggested by our results agree with the palaeogeography of the region. For this particular group of ants, the rapid orogenesis in New Guinea and possibly subsequent ecological shifts may have promoted their rapid diversification and widespread distribution across the Indo-Pacific.}, } @article {pmid29448062, year = {2018}, author = {Ali, JR}, title = {Geological data indicate that the interpretation for the age-calibrated phylogeny for the Kurixalus-genus frogs of South, South-east and East Asia (Lv et al., 2018) needs to be rethought.}, journal = {Molecular phylogenetics and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ympev.2018.02.011}, pmid = {29448062}, issn = {1095-9513}, abstract = {Recently, Lv et al. (2018) published an age-calibrated phylogenetic tree for the Kurixalus frogs, members of which occur across parts of South, South-east and East Asia. A clade on Taiwan, represented by Kurixalus idiootocus and the Kurixalus eiffingeri species complex, is deemed to have been resident since the middle Cenozoic; its closest congeners are in southern Indochina (not in the adjacent parts of south-east China), and the split between the two is dated at 32.8 Ma. Furthermore, a sub-population of Kurixalus eiffingeri is believed to have colonized islands in the western Ryukyus c. 13.5 Ma. There is, however, a problem with this scenario: the landmass regarded as modern-day Taiwan has existed only for 4-5 million years (it results from a young and ongoing tectonic-plate collision). Assuming the Kurixalus phylogeny and the dating of its branchings are correct, then a palaeobiogeographical scenario involving an older, alternative land surface with later transfer to Taiwan, possibly involving over-water dispersal, would reconcile the biology, but testing this may be difficult/impossible. If the ages of the nodes in the proposed tree are found to be significantly overestimated, the geology and biology might more easily be accommodated.}, } @article {pmid29447907, year = {2018}, author = {Glover, JC and Elliott, KL and Erives, A and Chizhikov, VV and Fritzsch, B}, title = {Wilhelm His' lasting insights into hindbrain and cranial ganglia development and evolution.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29447907}, issn = {1095-564X}, support = {R01 DC005590/DC/NIDCD NIH HHS/United States ; R01 NS093009/NS/NINDS NIH HHS/United States ; R03 DC015333/DC/NIDCD NIH HHS/United States ; }, abstract = {Wilhelm His (1831-1904) provided lasting insights into the development of the central and peripheral nervous system using innovative technologies such as the microtome, which he invented. 150 years after his resurrection of the classical germ layer theory of Wolff, von Baer and Remak, his description of the developmental origin of cranial and spinal ganglia from a distinct cell population, now known as the neural crest, has stood the test of time and more recently sparked tremendous advances regarding the molecular development of these important cells. In addition to his 1868 treatise on 'Zwischenstrang' (now neural crest), his work on the development of the human hindbrain published in 1890 provided novel ideas that more than 100 years later form the basis for penetrating molecular investigations of the regionalization of the hindbrain neural tube and of the migration and differentiation of its constituent neuron populations. In the first part of this review we briefly summarize the major discoveries of Wilhelm His and his impact on the field of embryology. In the second part we relate His' observations to current knowledge about the molecular underpinnings of hindbrain development and evolution. We conclude with the proposition, present already in rudimentary form in the writings of His, that a primordial spinal cord-like organization has been molecularly supplemented to generate hindbrain 'neomorphs' such as the cerebellum and the auditory and vestibular nuclei and their associated afferents and sensory organs.}, } @article {pmid29447906, year = {2018}, author = {Hara, Y and Sudo, T and Togane, Y and Akagawa, H and Tsujimura, H}, title = {Cell death in neural precursor cells and neurons before neurite formation prevents the emergence of abnormal neural structures in the Drosophila optic lobe.}, journal = {Developmental biology}, volume = {436}, number = {1}, pages = {28-41}, doi = {10.1016/j.ydbio.2018.02.004}, pmid = {29447906}, issn = {1095-564X}, mesh = {Animals ; Apoptosis/*physiology ; Caspases/metabolism ; Drosophila ; Drosophila Proteins/metabolism ; Immunohistochemistry ; Neural Stem Cells/cytology/metabolism/*physiology ; Neurites/physiology ; Neurogenesis/*physiology ; Neurons/metabolism/*physiology ; Optic Lobe, Nonmammalian/cytology/metabolism/*physiology ; Signal Transduction/physiology ; }, abstract = {Programmed cell death is a conserved strategy for neural development both in vertebrates and invertebrates and is recognized at various developmental stages in the brain from neurogenesis to adulthood. To understand the development of the central nervous system, it is essential to reveal not only molecular mechanisms but also the role of neural cell death (Pinto-Teixeira et al., 2016). To understand the role of cell death in neural development, we investigated the effect of inhibition of cell death on optic lobe development. Our data demonstrate that, in the optic lobe of Drosophila, cell death occurs in neural precursor cells and neurons before neurite formation and functions to prevent various developmental abnormalities. When neuronal cell death was inhibited by an effector caspase inhibitor, p35, multiple abnormal neuropil structures arose during optic lobe development-e.g., enlarged or fused neuropils, misrouted neurons and abnormal neurite lumps. Inhibition of cell death also induced morphogenetic defects in the lamina and medulla development-e.g., failures in the separation of the lamina and medulla cortices and the medulla rotation. These defects were reproduced in the mutant of an initiator caspase, dronc. If cell death was a mechanism for removing the abnormal neuropil structures, we would also expect to observe them in mutants defective for corpse clearance. However, they were not observed in these mutants. When dead cell-membranes were visualized with Apoliner, they were observed only in cortices and not in neuropils. These results suggest that the cell death occurs before mature neurite formation. Moreover, we found that inhibition of cell death induced ectopic neuroepithelial cells, neuroblasts and ganglion mother cells in late pupal stages, at sites where the outer and inner proliferation centers were located at earlier developmental stages. Caspase-3 activation was observed in the neuroepithelial cells and neuroblasts in the proliferation centers. These results indicate that cell death is required for elimination of the precursor cells composing the proliferation centers. This study substantiates an essential role of early neural cell death for ensuring normal development of the central nervous system.}, } @article {pmid29447764, year = {2018}, author = {Bruxelles, L and Maire, R and Beaudet, A and Couzens, R and Duranthon, F and Fourvel, JB and Stratford, D and Thackeray, F and Braga, J}, title = {Retraction notice to: The revised stratigraphy of the hominin-bearing site of Kromdraai (Gauteng, South Africa) and associated perspectives [J. Human Evol. 114 (2018) 1-19].}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {R1}, doi = {10.1016/j.jhevol.2018.02.001}, pmid = {29447764}, issn = {1095-8606}, } @article {pmid29447763, year = {2018}, author = {Boyer, DM and Harrington, AR}, title = {Scaling of bony canals for encephalic vessels in euarchontans: Implications for the role of the vertebral artery and brain metabolism.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {85-101}, doi = {10.1016/j.jhevol.2017.09.003}, pmid = {29447763}, issn = {1095-8606}, abstract = {Supplying the central nervous system with oxygen and glucose for metabolic activities is a critical function for all animals at physiologic, anatomical, and behavioral levels. A relatively proximate challenge to nourishing the brain is maintaining adequate blood flow. Euarchontans (primates, dermopterans and treeshrews) display a diversity of solutions to this challenge. Although the vertebral artery is a major encephalic vessel, previous research has questioned its importance for irrigating the cerebrum. This presents a puzzling scenario for certain strepsirrhine primates (non-cheirogaleid lemuriforms) that have reduced promontorial branches of the internal carotid artery and no apparent alternative encephalic vascular route except for the vertebral artery. Here, we present results of phylogenetic comparative analyses of data on the cross-sectional area of bony canals that transmit the vertebral artery (transverse foramina). These results show that, across primates (and within major primate subgroups), variation in the transverse foramina helps significantly to explain variation in forebrain mass even when variation in promontorial canal cross-sectional areas are also considered. Furthermore, non-cheirogaleid lemuriforms have larger transverse foramina for their endocranial volume than other euarchontans, suggesting that the vertebral arteries compensate for reduced promontorial artery size. We also find that, among internal carotid-reliant euarchontans, species that are more encephalized tend to have a promontorial canal that is larger relative to the transverse foramina. Tentatively, we consider the correlation between arterial canal diameters (as a proxy for blood flow) and brain metabolic demands. The results of this analysis imply that human investment in brain metabolism (∼27% of basal metabolic rate) may not be exceptional among euarchontans.}, } @article {pmid29447762, year = {2018}, author = {Li, F and Kuhn, SL and Chen, F and Wang, Y and Southon, J and Peng, F and Shan, M and Wang, C and Ge, J and Wang, X and Yun, T and Gao, X}, title = {The easternmost Middle Paleolithic (Mousterian) from Jinsitai Cave, North China.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {76-84}, doi = {10.1016/j.jhevol.2017.10.004}, pmid = {29447762}, issn = {1095-8606}, abstract = {The dispersal of Neanderthals and their genetic and cultural interactions with anatomically modern humans and other hominin populations in Eurasia are critical issues in human evolution research. Neither Neanderthal fossils nor typical Mousterian assemblages have been reported in East Asia to date. Here we report on artifact assemblages comparable to western Eurasian Middle Paleolithic (Mousterian) at Jinsitai, a cave site in North China. The lithic industry at Jinsitai appeared at least 47-42 ka and persisted until around 40-37 ka. These findings expand the geographic range of the Mousterian-like industries at least 2000 km further to the east than what has been previously recognized. This discovery supplies a missing part of the picture of Middle Paleolithic distribution in Eurasia and also demonstrates the makers' capacity to adapt to diverse geographic regions and habitats of Eurasia.}, } @article {pmid29447761, year = {2018}, author = {Kivell, TL and Rosas, A and Estalrrich, A and Huguet, R and García-Tabernero, A and Ríos, L and de la Rasilla, M}, title = {New Neandertal wrist bones from El Sidrón, Spain (1994-2009).}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {45-75}, doi = {10.1016/j.jhevol.2017.09.007}, pmid = {29447761}, issn = {1095-8606}, abstract = {Twenty-nine carpal bones of Homo neanderthalensis have been recovered from the site of El Sidrón (Asturias, Spain) during excavations between 1994 and 2009, alongside ∼2500 other Neandertal skeletal elements dated to ∼49,000 years ago. All bones of the wrist are represented, including adult scaphoids (n = 6), lunates (n = 2), triquetra (n = 4), pisiforms (n = 2), trapezia (n = 2), trapezoids (n = 5), capitates (n = 5), and hamates (n = 2), as well as one fragmentary and possibly juvenile scaphoid. Several of these carpals appear to belong to the complete right wrist of a single individual. Here we provide qualitative and quantitative morphological descriptions of these carpals, within a comparative context of other European and Near Eastern Neandertals, early and recent Homo sapiens, and other fossil hominins, including Homo antecessor, Homo naledi, and australopiths. Overall, the El Sidrón carpals show characteristics that typically distinguish Neandertals from H. sapiens, such as a relatively flat first metacarpal facet on the trapezium and a more laterally oriented second metacarpal facet on the capitate. However, there are some distinctive features of the El Sidrón carpals compared with most other Neandertals. For example, the tubercle of the trapezium is small with limited projection, while the scaphoid tubercle and hamate hamulus are among the largest seen in other Neandertals. Furthermore, three of the six adult scaphoids show a distinctive os-centrale portion, while another is a bipartite scaphoid with a truncated tubercle. The high frequency of rare carpal morphologies supports other evidence of a close genetic relationship among the Neandertals found at El Sidrón.}, } @article {pmid29447760, year = {2018}, author = {Chase, BM and Faith, JT and Mackay, A and Chevalier, M and Carr, AS and Boom, A and Lim, S and Reimer, PJ}, title = {Climatic controls on Later Stone Age human adaptation in Africa's southern Cape.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {35-44}, doi = {10.1016/j.jhevol.2017.09.006}, pmid = {29447760}, issn = {1095-8606}, abstract = {Africa's southern Cape is a key region for the evolution of our species, with early symbolic systems, marine faunal exploitation, and episodic production of microlithic stone tools taken as evidence for the appearance of distinctively complex human behavior. However, the temporally discontinuous nature of this evidence precludes ready assumptions of intrinsic adaptive benefit, and has encouraged diverse explanations for the occurrence of these behaviors, in terms of regional demographic, social and ecological conditions. Here, we present a new high-resolution multi-proxy record of environmental change that indicates that faunal exploitation patterns and lithic technologies track climatic variation across the last 22,300 years in the southern Cape. Conditions during the Last Glacial Maximum and deglaciation were humid, and zooarchaeological data indicate high foraging returns. By contrast, the Holocene is characterized by much drier conditions and a degraded resource base. Critically, we demonstrate that systems for technological delivery - or provisioning - were responsive to changing humidity and environmental productivity. However, in contrast to prevailing models, bladelet-rich microlithic technologies were deployed under conditions of high foraging returns and abandoned in response to increased aridity and less productive subsistence environments. This suggests that posited links between microlithic technologies and subsistence risk are not universal, and the behavioral sophistication of human populations is reflected in their adaptive flexibility rather than in the use of specific technological systems.}, } @article {pmid29447759, year = {2018}, author = {Forrest, FL and Plummer, TW and Raaum, RL}, title = {Ecomorphological analysis of bovid mandibles from Laetoli Tanzania using 3D geometric morphometrics: Implications for hominin paleoenvironmental reconstruction.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {20-34}, doi = {10.1016/j.jhevol.2017.09.010}, pmid = {29447759}, issn = {1095-8606}, abstract = {The current study describes a new method of mandibular ecological morphology (ecomorphology). Three-dimensional geometric morphometrics (3D GM) was used to quantify mandibular shape variation between extant bovids with different feeding preferences. Landmark data were subjected to generalized Procrustes analysis (GPA), principal components analysis (PCA), and discriminant function analysis (DFA). The PCA resulted in a continuum from grazers to browsers along PC1 and DFA classified 88% or more of the modern specimens to the correct feeding category. The protocol was reduced to a subset of landmarks on the mandibular corpus in order to make it applicable to incomplete fossils. The reduced landmark set resulted in greater overlap between feeding categories but maintained the same continuum as the complete landmark model. The DFA resubstitution and jackknife analyses resulted in classification success rates of 85% and 80%, respectively. The reduced landmark model was applied to fossil mandibles from the Upper Laetolil Beds (∼4.3-3.5 Ma) and Upper Ndolanya Beds (∼2.7-2.6 Ma) at Laetoli, Tanzania in order to assess antelope diet, and indirectly evaluate paleo-vegetation structure. The majority of the fossils were classified by the DFA as browsers or mixed feeders preferring browse. Our results indicate a continuous presence of wooded habitats and are congruent with recent environmental studies at Laetoli indicating a mosaic woodland-bushland-grassland savanna ecosystem.}, } @article {pmid29447758, year = {2018}, author = {Rossie, JB and Smith, TD and Beard, KC and Godinot, M and Rowe, TB}, title = {Nasolacrimal anatomy and haplorhine origins.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {176-183}, doi = {10.1016/j.jhevol.2017.11.004}, pmid = {29447758}, issn = {1095-8606}, abstract = {Computed tomography X-ray imaging of the internal face in well-preserved primate fossil crania permits reconstruction of the nature of their nasal anatomy, including some soft-tissue features. These features are diagnostic of the primate suborder Haplorhini, and allow reevaluation of the phylogenetic status of several purported early members of the group. Here we examine the nasolacrimal morphology of a broad sample of extant primates, as well as a number of Paleogene fossils. The extant sample confirms the distinctiveness of the two suborders. Of the fossils studied, only Shoshonius cooperi from the late-early Eocene exhibits evidence of a haplorhine nose. This suggests that the haplorhine oronasal complex may have evolved before the postorbital septum, and strengthens the claim that Shoshonius is a close relative of tarsiers and anthropoids. These results indicate that Omomyiformes is not a monophyletic group, and that few of its members possessed the derived oronasal morphology that characterizes crown haplorhines.}, } @article {pmid29447757, year = {2018}, author = {Stelzer, S and Gunz, P and Neubauer, S and Spoor, F}, title = {Using the covariation of extant hominoid upper and lower jaws to predict dental arcades of extinct hominins.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {154-175}, doi = {10.1016/j.jhevol.2017.10.012}, pmid = {29447757}, issn = {1095-8606}, abstract = {Upper and lower jaws are well represented in the fossil record of mammals and are frequently used to diagnose species. Some hominin species are only known by either their maxillary or mandibular morphology, and in this study, we explore the possibility of predicting their complementary dental arcade shape to aid the recognition of conspecific specimens in the fossil record. To this end, we apply multiple multivariate regression to analyze 3D landmark coordinates collected on associated upper and lower dental arcades of extant Homo, Pan, Gorilla, Pongo, and Hylobates. We first study the extant patterns of variation in dental arcade shape and quantify how accurate predictions of complementary arcades are. Then we explore applications of this extant framework for interpreting the fossil record based on two fossil hominin specimens with associated upper and lower jaws, KNM-WT 15000 (Homo erectus sensu lato) and Sts 52 (Australopithecus africanus), as well as two non-associated specimens of Paranthropus boisei, the maxilla of OH 5 and the Peninj mandible. We find that the shape differences between the predictions and the original fossil specimens are in the range of variation within genera or species and therefore are consistent with their known affinity. Our approach can provide a reference against which intraspecific variation of extinct species can be assessed. We show that our method predicts arcade shapes reliably even if the target shape is not represented in the reference sample. We find that in extant hominoids, the amount of within-taxon variation in dental arcade shape often overlaps with the amount of between-taxon shape variation. This implies that whereas a large difference in dental arcade shape between two individuals typically suggests that they belong to different species or even genera, a small shape difference does not necessarily imply conspecificity.}, } @article {pmid29447756, year = {2018}, author = {Godinho, RM and O'Higgins, P}, title = {The biomechanical significance of the frontal sinus in Kabwe 1 (Homo heidelbergensis).}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {141-153}, doi = {10.1016/j.jhevol.2017.10.007}, pmid = {29447756}, issn = {1095-8606}, abstract = {Paranasal sinuses are highly variable among living and fossil hominins and their function(s) are poorly understood. It has been argued they serve no particular function and are biological 'spandrels' arising as a structural consequence of changes in associated bones and/or soft tissue structures. In contrast, others have suggested that sinuses have one or more functions, in olfaction, respiration, thermoregulation, nitric oxide production, voice resonance, reduction of skull weight, and craniofacial biomechanics. Here we assess the extent to which the very large frontal sinus of Kabwe 1 impacts on the mechanical performance of the craniofacial skeleton during biting. It may be that the browridge is large and the sinus has large trabecular struts traversing it to compensate for the effect of a large sinus on the ability of the face to resist forces arising from biting. Alternatively, the large sinus may have no impact and be sited where strains that arise from biting would be very low. If the former is true, then infilling of the sinus would be expected to increase the ability of the skeleton to resist biting loads, while removing the struts might have the opposite effect. To these ends, finite element models with hollowed and infilled variants of the original sinus were created and loaded to simulate different bites. The deformations arising due to loading were then compared among different models and bites by contrasting the strain vectors arising during identical biting tasks. It was found that the frontal bone experiences very low strains and that infilling or hollowing of the sinus has little effect on strains over the cranial surface, with small effects over the frontal bone. The material used to infill the sinus experienced very low strains. This is consistent with the idea that frontal sinus morphogenesis is influenced by the strain field experienced by this region such that it comes to lie entirely within a region of the cranium that would otherwise experience low strains. This has implications for understanding why sinuses vary among hominin fossils.}, } @article {pmid29447755, year = {2018}, author = {Walker, KK and Walker, CS and Goodall, J and Pusey, AE}, title = {Maturation is prolonged and variable in female chimpanzees.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {131-140}, pmid = {29447755}, issn = {1095-8606}, support = {R01 AI058715/AI/NIAID NIH HHS/United States ; }, abstract = {Chimpanzees are important referential models for the study of life history in hominin evolution. Age at sexual maturity and first reproduction are key life history milestones that mark the diversion of energy from growth to reproduction and are essential in comparing life history trajectories between chimpanzees and humans. Yet, accurate information on ages at these milestones in wild chimpanzees is difficult to obtain because most females transfer before breeding. Precise age at first birth is only known from a relatively small number of non-dispersing individuals. Moreover, due to small sample sizes, the degree to which age at maturation milestones varies is unknown. Here we report maturation milestones and explore sources of variance for 36 wild female chimpanzees of known age, including eight dispersing females born in Gombe National Park, Tanzania. Using Kaplan-Meier survival analysis, including censored intervals, we find an average age of 11.5 years (range 8.5-13.9) at sexual maturity and 14.9 years (range 11.1-22.1) at first birth. These values exceed previously published averages for wild chimpanzees by one or more years. Even in this larger sample, age at first birth is likely underestimated due to the disproportionate number of non-dispersing females, which, on average, give birth two years earlier than dispersing females. Model selection using Cox Proportional Hazards models shows that age at sexual maturity is delayed in females orphaned before age eight years and those born to low-ranking mothers. Age at first birth is most delayed in dispersing females and those orphaned before age eight years. These data provide improved estimates of maturation milestones in a population of wild female chimpanzees and indicate the importance of maternal factors in development.}, } @article {pmid29447754, year = {2018}, author = {Sillen, A and Balter, V}, title = {Strontium isotopic aspects of Paranthropus robustus teeth; implications for habitat, residence, and growth.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {118-130}, doi = {10.1016/j.jhevol.2017.09.009}, pmid = {29447754}, issn = {1095-8606}, abstract = {The strontium isotopic ratio 87Sr/86Sr has been studied in the Sterkfontein Valley of South Africa to infer both habitat usage and residence for a number of early hominins. This paper examines the existing 87Sr/86Sr data collectively derived from three studies of Paranthropus robustus teeth with the aim of exploring whether the dataset as a whole may provide deeper insight into habitat, mobility, and growth for this species. 87Sr/86Sr from seven Swartkrans Member I third molars varies in a well defined narrow range, and while some canines were consistent with this range, a number of P. robustus canines and first and second molars were not, and therefore represent individuals who had arrived from other localities. A first and third molar 87Sr/86Sr was found to differ in TM1517c, the holotype P. robustus specimen from Kromdraai, suggesting this individual had moved to the locality sometime after the first molar and before the third molar had completely mineralized. While early forming teeth vary widely, the relatively low variation and absence of exogenous 87Sr/86Sr in third molars suggest that these teeth mineralized relatively late when compared to life history events bearing on higher primate residence patterns. The implications for further study of habitat, residence, and growth are discussed.}, } @article {pmid29447753, year = {2018}, author = {Orr, CM}, title = {Kinematics of the anthropoid os centrale and the functional consequences of scaphoid-centrale fusion in African apes and hominins.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {102-117}, doi = {10.1016/j.jhevol.2017.10.002}, pmid = {29447753}, issn = {1095-8606}, abstract = {In most primates, the os centrale is interposed between the scaphoid, trapezoid, trapezium, and head of the capitate, thus constituting a component of the wrist's midcarpal complex. Scaphoid-centrale fusion is among the clearest morphological synapomorphies of African apes and hominins. Although it might facilitate knuckle-walking by increasing the rigidity and stability of the radial side of the wrist, the exact functional significance of scaphoid-centrale fusion is unclear. If fusion acts to produce a more rigid radial wrist that stabilizes the hand and limits shearing stresses, then in taxa with a free centrale, it should anchor ligaments that check extension and radial deviation, but exhibit motion independent of the scaphoid. Moreover, because the centrale sits between the scaphoid and capitate (a major stabilizing articulation), scaphoid-centrale mobility should correlate with scaphocapitate mobility in extension and radial deviation. To test these hypotheses, the centrale's ligamentous binding was investigated via dissection in Pongo and Papio, and the kinematics of the centrale were quantified in a cadaveric sample of anthropoids (Pongo sp., Ateles geoffroyi, Colobus guereza, Macaca mulatta, and Papio anubis) using a computed-tomography-based method to track wrist-bone motion. Results indicate that the centrale rotates freely relative to the scaphoid in all taxa. However, centrale mobility is only correlated with scaphocapitate mobility during extension in Pongo-possibly due to differences in overall wrist configuration between apes and monkeys. If an extant ape-like wrist characterized early ancestors of African apes and hominins, then scaphoid-centrale fusion would have increased midcarpal rigidity in extension relative to the primitive condition. Although biomechanically consistent with a knuckle-walking hominin ancestor, this assumes that the trait evolved specifically for that biological role, which must be squared with contradictory interpretations of extant and fossil hominoid morphology. Regardless of its original adaptive significance, scaphoid-centrale fusion likely presented a constraint on early hominin midcarpal mobility.}, } @article {pmid29447752, year = {2018}, author = {Bruxelles, L and Maire, R and Beaudet, A and Couzens, R and Duranthon, F and Fourvel, JB and Stratford, D and Thackeray, F and Braga, J}, title = {RETRACTED: The revised stratigraphy of the hominin-bearing site of Kromdraai (Gauteng, South Africa) and associated perspectives.}, journal = {Journal of human evolution}, volume = {114}, number = {}, pages = {1-19}, doi = {10.1016/j.jhevol.2017.09.005}, pmid = {29447752}, issn = {1095-8606}, abstract = {This article has been retracted: please see Elsevier Policy on Article Withdrawal (http://www.elsevier.com/locate/withdrawalpolicy). This article has been retracted at the request of the co-Editors-in-Chief and the authors. The Results and Discussion of this article duplicate significant parts of book chapter "A revised stratigraphy of Kromdraai", published by L.B., R.M., R.C., F.T. and J.B. in Braga, J. and Thackeray, J.F. (Eds.), "Kromdraai. A Birthplace of Paranthropus in the Cradle of Humankind" (2016, SUN MeDIA MeTRO, pp. 31-47), https://doi.org/10.18820/9781928355076. One of the conditions of submission of a paper to Journal of Human Evolution is that authors declare explicitly that that their work is original and has not been published previously. Reuse of any data should be appropriately cited. As such this article represents an abuse of the scientific publishing system. The scientific community takes a very strong view on this matter and apologies are offered to readers of the journal that this was not detected during the submission process.}, } @article {pmid29447391, year = {2018}, author = {Holthaus, KB and Strasser, B and Lachner, J and Sukseree, S and Sipos, W and Weissenbacher, A and Tschachler, E and Alibardi, L and Eckhart, L}, title = {Comparative analysis of epidermal differentiation genes of crocodilians suggests new models for the evolutionary origin of avian feather proteins.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29447391}, issn = {1759-6653}, abstract = {The epidermis of amniotes forms a protective barrier against the environment and the differentiation program of keratinocytes, the main cell type in the epidermis, has undergone specific alterations in the course of adaptation of amniotes to a broad variety of environments and lifestyles. The epidermal differentiation complex (EDC) is a cluster of genes expressed at late stages of keratinocyte differentiation in both sauropsids and mammals. In the present study we identified and analyzed the crocodilian equivalent of the EDC. The gene complement of the EDC of both the American alligator and the saltwater crocodile were determined by comparative genomics, de novo gene prediction and identification of EDC transcripts in published transcriptome data. We found that crocodilians have an organization of the EDC similar to that of their closest living relatives, the birds, with which they form the clade Archosauria. Notable differences include the specific expansion of a subfamily of EDC genes in crocodilians and the loss of distinct ancestral EDC genes in birds. Identification and comparative analysis of crocodilian orthologs of avian feather proteins suggest that the latter evolved by cooption and sequence modification of ancestral EDC genes, and that the amplification of an internal highly cysteine-enriched amino acid sequence motif gave rise to the feather component Epidermal Differentiation Cysteine Rich Protein (EDCRP) in the avian lineage. Thus, sequence diversification of EDC genes contributed to the evolutionary divergence of the crocodilian and avian integuments.}, } @article {pmid29447366, year = {2018}, author = {Kincaid-Smith, J and Picard, MAL and Cosseau, C and Boissier, J and Severac, D and Grunau, C and Toulza, E}, title = {Parent-of-Origin-Dependent Gene Expression in Male and Female Schistosome Parasites.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {840-856}, pmid = {29447366}, issn = {1759-6653}, mesh = {Alleles ; Animals ; *Biological Evolution ; Female ; Humans ; Male ; Schistosoma mansoni/*genetics/pathogenicity ; Schistosomiasis/*genetics/parasitology ; Sex Characteristics ; Sex Determination Processes/*genetics ; }, abstract = {Schistosomes are the causative agents of schistosomiasis, a neglected tropical disease affecting over 230 million people worldwide. Additionally to their major impact on human health, they are also models of choice in evolutionary biology. These parasitic flatworms are unique among the common hermaphroditic trematodes as they have separate sexes. This so-called "evolutionary scandal" displays a female heterogametic genetic sex-determination system (ZZ males and ZW females), as well as a pronounced adult sexual dimorphism. These phenotypic differences are determined by a shared set of genes in both sexes, potentially leading to intralocus sexual conflicts. To resolve these conflicts in sexually selected traits, molecular mechanisms such as sex-biased gene expression could occur, but parent-of-origin gene expression also provides an alternative. In this work we investigated the latter mechanism, that is, genes expressed preferentially from either the maternal or the paternal allele, in Schistosoma mansoni species. To this end, transcriptomes from male and female hybrid adults obtained by strain crosses were sequenced. Strain-specific single nucleotide polymorphism (SNP) markers allowed us to discriminate the parental origin, while reciprocal crosses helped to differentiate parental expression from strain-specific expression. We identified genes containing SNPs expressed in a parent-of-origin manner consistent with paternal and maternal imprints. Although the majority of the SNPs was identified in mitochondrial and Z-specific loci, the remaining SNPs found in male and female transcriptomes were situated in genes that have the potential to explain sexual differences in schistosome parasites. Furthermore, we identified and validated four new Z-specific scaffolds.}, } @article {pmid29447350, year = {2018}, author = {Geisen, S and Mitchell, EAD and Adl, S and Bonkowski, M and Dunthorn, M and Ekelund, F and Fernández, LD and Jousset, A and Krashevska, V and Singer, D and Spiegel, FW and Walochnik, J and Lara, E}, title = {Soil protists: a fertile frontier in soil biology research.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {293-323}, doi = {10.1093/femsre/fuy006}, pmid = {29447350}, issn = {1574-6976}, mesh = {Animals ; Biodiversity ; Eukaryota/*physiology ; Food Chain ; Research/*trends ; Soil/*parasitology ; }, abstract = {Protists include all eukaryotes except plants, fungi and animals. They are an essential, yet often forgotten, component of the soil microbiome. Method developments have now furthered our understanding of the real taxonomic and functional diversity of soil protists. They occupy key roles in microbial foodwebs as consumers of bacteria, fungi and other small eukaryotes. As parasites of plants, animals and even of larger protists, they regulate populations and shape communities. Pathogenic forms play a major role in public health issues as human parasites, or act as agricultural pests. Predatory soil protists release nutrients enhancing plant growth. Soil protists are of key importance for our understanding of eukaryotic evolution and microbial biogeography. Soil protists are also useful in applied research as bioindicators of soil quality, as models in ecotoxicology and as potential biofertilizers and biocontrol agents. In this review, we provide an overview of the enormous morphological, taxonomical and functional diversity of soil protists, and discuss current challenges and opportunities in soil protistology. Research in soil biology would clearly benefit from incorporating more protistology alongside the study of bacteria, fungi and animals.}, } @article {pmid29446563, year = {2018}, author = {Kamilar, JM}, title = {The Evolution of Evolutionary Anthropology.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {2}, doi = {10.1002/evan.21576}, pmid = {29446563}, issn = {1520-6505}, mesh = {*Anthropology ; *Biological Evolution ; Humans ; Periodicals as Topic ; }, } @article {pmid29446562, year = {2018}, author = {Chandrashekar, A and Raboin, DL}, title = {The 40th meeting of the American Society of Primatologists.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {7-8}, doi = {10.1002/evan.21572}, pmid = {29446562}, issn = {1520-6505}, } @article {pmid29446561, year = {2018}, author = {Riede, F and Johannsen, NN and Högberg, A and Nowell, A and Lombard, M}, title = {The role of play objects and object play in human cognitive evolution and innovation.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {46-59}, pmid = {29446561}, issn = {1520-6505}, mesh = {Adolescent ; Adult ; Archaeology ; *Biological Evolution ; Child ; *Cognition ; *Creativity ; History, Ancient ; Humans ; *Play and Playthings ; Technology/*history ; }, abstract = {In this contribution, we address a major puzzle in the evolution of human material culture: If maturing individuals just learn their parental generation's material culture, then what is the origin of key innovations as documented in the archeological record? We approach this question by coupling a life-history model of the costs and benefits of experimentation with a niche-construction perspective. Niche-construction theory suggests that the behavior of organisms and their modification of the world around them have important evolutionary ramifications by altering developmental settings and selection pressures. Part of Homo sapiens' niche is the active provisioning of children with play objects - sometimes functional miniatures of adult tools - and the encouragement of object play, such as playful knapping with stones. Our model suggests that salient material culture innovation may occur or be primed in a late childhood or adolescence sweet spot when cognitive and physical abilities are sufficiently mature but before the full onset of the concerns and costs associated with reproduction. We evaluate the model against a series of archeological cases and make suggestions for future research.}, } @article {pmid29446560, year = {2018}, author = {Hosfield, R and Cole, J and McNabb, J}, title = {Less of a bird's song than a hard rock ensemble.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {9-20}, doi = {10.1002/evan.21551}, pmid = {29446560}, issn = {1520-6505}, mesh = {Africa ; Animals ; Archaeology ; Europe ; Female ; History, Ancient ; Hominidae/*physiology ; Humans ; Male ; Technology/*history ; Tool Use Behavior/*physiology ; }, abstract = {Corbey et al. (2016) propose that the Acheulean handaxe was, at least in part, under genetic control. An alternative perspective is offered here, focusing on the nature of the Acheulean handaxe and the archaeological record, and re-emphasizing their status as cultural artefacts. This is based on four main arguments challenging the proposals of Corbey et al. Firstly, handaxes do not have to track environmental variation to be a cultural artefact, given their role as a hand-held butchery knife or multi-purpose tool. Secondly, while handaxe shapes do cluster around a basic bauplan, there is also significant variability in the Acheulean handaxe record, characterized by site-specific modal forms and locally expressed, short-lived, idiosyncratic traits. Critically, this variability occurs in both time and space, is multi-scalar, and does not appear to be under genetic control. Thirdly, handaxes were produced in social contexts, within which their makers grew up exposed to the sights and sounds of artefact manufacture. Finally, the localized absences of handaxes at different times and places in the Lower Paleolithic world is suggestive of active behavioral choices and population dynamics rather than genetic controls.}, } @article {pmid29446559, year = {2018}, author = {Wynn, T and Gowlett, J}, title = {The handaxe reconsidered.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {21-29}, doi = {10.1002/evan.21552}, pmid = {29446559}, issn = {1520-6505}, mesh = {Animals ; Archaeology ; Ergonomics/*history ; Esthetics/*history ; History, Ancient ; Hominidae/*physiology ; Technology/*history ; Tool Use Behavior/*physiology ; }, abstract = {The Acheulean handaxe is one of the longest-known and longest-surviving artifacts of the Palaeolithic and, despite its experimentally tested functionality, is often regarded as puzzling. It is unnecessary to invoke a unique-for-mammals genetic mechanism to explain the handaxe phenomenon. Instead, we propose that two nongenetic processes are sufficient. The first is a set of ergonomic design principles linked to the production of sturdy, hand-held cutting tools in the context of a knapped-stone technology that lacked hafting. The second is an esthetic preference for regular forms with gradual curves and pleasing proportions. Neither process is a cultural meme but, operating together in a cultural context, they can account for all of the supposedly puzzling time-space patterns presented by handaxes.}, } @article {pmid29446558, year = {2018}, author = {Mori, T and Beier, J and de Matos, D and Mentzer, SM}, title = {Seventh Annual Meeting of the European Society for the Study of Human Evolution.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {3-4}, doi = {10.1002/evan.21564}, pmid = {29446558}, issn = {1520-6505}, } @article {pmid29446557, year = {2018}, author = {Henry, AG and Devereux, E and Bartholdy, BP}, title = {European Society for the Study of Human Evolution 2017: old sites, new methods.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {5-6}, doi = {10.1002/evan.21571}, pmid = {29446557}, issn = {1520-6505}, } @article {pmid29446556, year = {2018}, author = {O'Driscoll, CA and Thompson, JC}, title = {The origins and early elaboration of projectile technology.}, journal = {Evolutionary anthropology}, volume = {27}, number = {1}, pages = {30-45}, doi = {10.1002/evan.21560}, pmid = {29446556}, issn = {1520-6505}, mesh = {Animals ; Bone and Bones/pathology ; History, Ancient ; Humans ; Neanderthals/*physiology ; Predatory Behavior/*physiology ; Technology/*history ; Tool Use Behavior/*physiology ; }, abstract = {The ability of Homo sapiens to kill prey at a distance is arguably one of the catalysts for our current ecological dominance. Many researchers have suggested its origins lie in the African Middle Stone Age or the European Middle Palaeolithic (∼300-30 thousand years ago), but the perishable components of armatures rarely preserve. Most research on this subject therefore emphasises analysis of armature tip size, shape, and diagnostic impacts or residues. Other lines of evidence have included human skeletal anatomy or analyses of the species composition of faunal assemblages. Projectile Impact Marks (PIMs) on archaeofaunal remains offer an ideal complement to this work, but their potential has been restricted mainly to the later Eurasian zooarchaeological record. A review of current evidence and approaches shows that systematic PIM research could add much to our understanding of early projectile technology, especially in Africa.}, } @article {pmid29446412, year = {2018}, author = {}, title = {From proposals to snarks: the messages that scientists sneak into their papers.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {276}, doi = {10.1038/d41586-018-01876-8}, pmid = {29446412}, issn = {1476-4687}, } @article {pmid29446411, year = {2018}, author = {Jaynes, AN}, title = {The origin of pulsating auroras.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {302-303}, doi = {10.1038/d41586-018-01669-z}, pmid = {29446411}, issn = {1476-4687}, } @article {pmid29446410, year = {2018}, author = {Friesike, S and Fecher, B and Wagner, GG}, title = {Teach young scientists the importance of societal impact for research.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {300}, doi = {10.1038/d41586-018-02066-2}, pmid = {29446410}, issn = {1476-4687}, mesh = {Humans ; *Research ; *Research Personnel ; }, } @article {pmid29446409, year = {2018}, author = {Watto, MA and Bashir, S and Khan Niazi, N}, title = {Better management of groundwater needed in Pakistan.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {300}, doi = {10.1038/d41586-018-02065-3}, pmid = {29446409}, issn = {1476-4687}, mesh = {*Environmental Monitoring ; *Groundwater ; Humans ; Pakistan ; Water Pollutants, Chemical/analysis ; }, } @article {pmid29446408, year = {2018}, author = {Howe, WM and Kenny, PJ}, title = {Burst firing sets the stage for depression.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {304-305}, doi = {10.1038/d41586-018-01588-z}, pmid = {29446408}, issn = {1476-4687}, mesh = {*Action Potentials ; *Depression ; Depressive Disorder ; Humans ; Neurons ; }, } @article {pmid29446407, year = {2018}, author = {}, title = {SpaceX ignites big dreams.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {275}, doi = {10.1038/d41586-018-01877-7}, pmid = {29446407}, issn = {1476-4687}, mesh = {Astronauts ; History, 20th Century ; History, 21st Century ; Industry/economics/trends ; Space Flight/economics/history/*instrumentation/*trends ; Spacecraft/economics/history/*instrumentation ; Travel/*economics/*trends ; }, } @article {pmid29446405, year = {2018}, author = {}, title = {Spaceflight success, harassment policy and ancestry research.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {280-281}, doi = {10.1038/d41586-018-01852-2}, pmid = {29446405}, issn = {1476-4687}, } @article {pmid29446404, year = {2018}, author = {Laursen, L}, title = {Wild primates threaten efforts to wipe out skin disease.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {286}, doi = {10.1038/d41586-018-01703-0}, pmid = {29446404}, issn = {1476-4687}, mesh = {Animals ; Humans ; *Primates ; *Skin Diseases ; }, } @article {pmid29446401, year = {2018}, author = {Busse, L}, title = {Working memory freed from the past.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {306-307}, doi = {10.1038/d41586-018-01418-2}, pmid = {29446401}, issn = {1476-4687}, mesh = {Humans ; *Memory, Short-Term ; }, } @article {pmid29446400, year = {2018}, author = {Watanabe, Y}, title = {Japanese photo of Rosalind Franklin unearthed.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {300}, doi = {10.1038/d41586-018-01830-8}, pmid = {29446400}, issn = {1476-4687}, mesh = {DNA/chemistry/history ; Graphite/chemistry/history ; History, 20th Century ; Japan ; London ; Periodicals as Topic/history ; Photography/*history ; }, } @article {pmid29446399, year = {2018}, author = {Chapron, G and Epstein, Y and López-Bao, JV}, title = {US bill illustrates how conservation triage can lead to extinctions.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {300}, doi = {10.1038/d41586-018-02064-4}, pmid = {29446399}, issn = {1476-4687}, mesh = {Algorithms ; Animals ; Conservation of Natural Resources/*economics/*legislation & jurisprudence/methods ; *Extinction, Biological ; *Federal Government ; United States ; }, } @article {pmid29446398, year = {2018}, author = {Mourigal, M}, title = {The two faces of a magnetic honeycomb.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {307-308}, doi = {10.1038/d41586-018-01747-2}, pmid = {29446398}, issn = {1476-4687}, } @article {pmid29446397, year = {2018}, author = {}, title = {Corrections.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {288}, doi = {10.1038/d41586-018-01878-6}, pmid = {29446397}, issn = {1476-4687}, } @article {pmid29446396, year = {2018}, author = {Carswell, C}, title = {Tree rings reveal increased fire risk for southwestern US.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {283-284}, doi = {10.1038/d41586-018-01686-y}, pmid = {29446396}, issn = {1476-4687}, mesh = {Altitude ; Arizona ; *Climate ; Forecasting/*methods ; Forestry/methods ; *Forests ; New Mexico ; Rain ; Risk Assessment/methods ; Snow ; Southwestern United States ; Trees/*growth & development ; Water Movements ; Wildfires/*statistics & numerical data ; Wood/*analysis ; }, } @article {pmid29446395, year = {2018}, author = {Sohn, E}, title = {A guide to juggling fieldwork and pregnancy.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {393-395}, doi = {10.1038/d41586-018-01851-3}, pmid = {29446395}, issn = {1476-4687}, mesh = {Africa ; Animals ; Career Choice ; Disclosure ; *Expeditions ; Female ; Health Services Accessibility ; Humans ; Patient Advocacy ; Pregnancy/*physiology ; Pregnancy Complications ; Prejudice ; *Research Design ; Research Personnel/*psychology ; *Risk Reduction Behavior ; Travel ; Venous Thrombosis/complications ; Wilderness ; }, } @article {pmid29446394, year = {2018}, author = {Castelvecchi, D}, title = {The quantum internet has arrived (and it hasn't).}, journal = {Nature}, volume = {554}, number = {7692}, pages = {289-292}, doi = {10.1038/d41586-018-01835-3}, pmid = {29446394}, issn = {1476-4687}, } @article {pmid29446392, year = {2018}, author = {Morello, L and Guglielmi, G and Reardon, S and Tollefson, J and Witze, A}, title = {Trump science budget sows confusion.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {284-285}, doi = {10.1038/d41586-018-01985-4}, pmid = {29446392}, issn = {1476-4687}, mesh = {Biomedical Research/economics/legislation & jurisprudence ; Budgets/*legislation & jurisprudence ; National Institutes of Health (U.S.)/economics ; Science/*economics/*legislation & jurisprudence ; United States ; United States Environmental Protection Agency/economics/legislation & jurisprudence ; United States Government Agencies/*economics/*legislation & jurisprudence ; United States National Aeronautics and Space Administration/economics/legislation & jurisprudence ; }, } @article {pmid29446391, year = {2018}, author = {}, title = {Watch your language.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {395}, doi = {10.1038/d41586-018-01850-4}, pmid = {29446391}, issn = {1476-4687}, mesh = {Advertising as Topic/*methods ; Authorship ; *Career Choice ; *Communication ; Female ; Humans ; Intelligence ; Internship and Residency ; *Job Application ; *Language ; Leadership ; Male ; *Motivation ; Research Personnel/education/*psychology ; *Sex Characteristics ; Sex Factors ; Students/psychology ; Surveys and Questionnaires ; }, } @article {pmid29446390, year = {2018}, author = {Witze, A}, title = {US science agency will require universities to report sexual harassment.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {287-288}, doi = {10.1038/d41586-018-01744-5}, pmid = {29446390}, issn = {1476-4687}, mesh = {Faculty/legislation & jurisprudence ; Female ; Financing, Organized/organization & administration ; Humans ; Male ; Sexual Harassment/*legislation & jurisprudence/prevention & control ; Students ; United States ; United States Government Agencies/*legislation & jurisprudence ; Universities/*legislation & jurisprudence ; }, } @article {pmid29446389, year = {2018}, author = {Wild, S}, title = {Deluge of astronomical data will soon hit South Africa.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {286-287}, doi = {10.1038/d41586-018-01838-0}, pmid = {29446389}, issn = {1476-4687}, mesh = {Astronomy/economics/*trends ; Australia ; Database Management Systems/economics/trends ; *Databases, Factual ; Electronic Data Processing/economics/*trends ; Software ; South Africa ; Telescopes/economics/*statistics & numerical data ; Workforce ; }, } @article {pmid29446388, year = {2018}, author = {Bosch, G}, title = {Train PhD students to be thinkers not just specialists.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {277}, doi = {10.1038/d41586-018-01853-1}, pmid = {29446388}, issn = {1476-4687}, mesh = {Achievement ; Career Mobility ; Communication ; Education, Graduate/*methods/*trends ; Efficiency ; Ethics, Research ; Female ; Humans ; Knowledge ; Leadership ; Logic ; Male ; Mentoring ; Morals ; Pilot Projects ; Reproducibility of Results ; Research/*education/*standards ; Research Design/standards ; Research Personnel/*education/*psychology/standards ; Software ; *Specialization ; Teaching ; *Thinking ; }, } @article {pmid29446387, year = {2018}, author = {Micalizzi, DS and Maheswaran, S}, title = {On the trail of invasive cells in breast cancer.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {308-309}, doi = {10.1038/d41586-018-01634-w}, pmid = {29446387}, issn = {1476-4687}, mesh = {Apoptosis ; *Breast Neoplasms ; Cell Line, Tumor ; Humans ; *Neoplasm Invasiveness ; }, } @article {pmid29446386, year = {2018}, author = {}, title = {Don't jump to conclusions about climate change and civil conflict.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {275-276}, doi = {10.1038/d41586-018-01875-9}, pmid = {29446386}, issn = {1476-4687}, mesh = {Africa ; Bias ; Climate Change/*statistics & numerical data ; *Conflict (Psychology) ; Developing Countries/statistics & numerical data ; Humans ; Social Justice ; Social Sciences/methods/standards ; *Uncertainty ; Violence/*statistics & numerical data ; Vulnerable Populations ; *Warfare ; Weather ; }, } @article {pmid29446385, year = {2018}, author = {Whiten, A}, title = {Brainpower boost for birds in large groups.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {303-304}, doi = {10.1038/d41586-018-01487-3}, pmid = {29446385}, issn = {1476-4687}, mesh = {Animals ; *Birds ; Brain/*physiology ; }, } @article {pmid29446384, year = {2018}, author = {Bellantuono, I}, title = {Find drugs that delay many diseases of old age.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {293-295}, doi = {10.1038/d41586-018-01668-0}, pmid = {29446384}, issn = {1476-4687}, mesh = {Age Distribution ; Aged ; Aged, 80 and over ; Aging/*drug effects/pathology/physiology ; Alzheimer Disease/epidemiology/prevention & control ; Animals ; Biomarkers, Pharmacological ; Chronic Disease/epidemiology/*prevention & control ; Diabetes Mellitus/epidemiology/prevention & control ; Disease Models, Animal ; Frail Elderly/statistics & numerical data ; Humans ; Longevity/*drug effects ; Mice ; Multimorbidity ; Neoplasms/epidemiology/prevention & control ; Rejuvenation/*physiology ; Time Factors ; }, } @article {pmid29446383, year = {2018}, author = {Ryan, BJ}, title = {Coordinate international Earth observations for maximum impact.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {300}, doi = {10.1038/d41586-018-02067-1}, pmid = {29446383}, issn = {1476-4687}, } @article {pmid29446382, year = {2018}, author = {Kitagawa, K and Takayama, T and Matsumoto, Y and Kato, A and Takano, R and Kishimoto, Y and Bette, S and Dinnebier, R and Jackeli, G and Takagi, H}, title = {A spin-orbital-entangled quantum liquid on a honeycomb lattice.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {341-345}, pmid = {29446382}, issn = {1476-4687}, abstract = {The honeycomb lattice is one of the simplest lattice structures. Electrons and spins on this simple lattice, however, often form exotic phases with non-trivial excitations. Massless Dirac fermions can emerge out of itinerant electrons, as demonstrated experimentally in graphene, and a topological quantum spin liquid with exotic quasiparticles can be realized in spin-1/2 magnets, as proposed theoretically in the Kitaev model. The quantum spin liquid is a long-sought exotic state of matter, in which interacting spins remain quantum-disordered without spontaneous symmetry breaking. The Kitaev model describes one example of a quantum spin liquid, and can be solved exactly by introducing two types of Majorana fermion. Realizing a Kitaev model in the laboratory, however, remains a challenge in materials science. Mott insulators with a honeycomb lattice of spin-orbital-entangled pseudospin-1/2 moments have been proposed, including the 5d-electron systems α-Na2IrO3 (ref. 5) and α-Li2IrO3 (ref. 6) and the 4d-electron system α-RuCl3 (ref. 7). However, these candidates were found to magnetically order rather than form a liquid at sufficiently low temperatures, owing to non-Kitaev interactions. Here we report a quantum-liquid state of pseudospin-1/2 moments in the 5d-electron honeycomb compound H3LiIr2O6. This iridate does not display magnetic ordering down to 0.05 kelvin, despite an interaction energy of about 100 kelvin. We observe signatures of low-energy fermionic excitations that originate from a small number of spin defects in the nuclear-magnetic-resonance relaxation and the specific heat. We therefore conclude that H3LiIr2O6 is a quantum spin liquid. This result opens the door to finding exotic quasiparticles in a strongly spin-orbit-coupled 5d-electron transition-metal oxide.}, } @article {pmid29446381, year = {2018}, author = {Yang, Y and Cui, Y and Sang, K and Dong, Y and Ni, Z and Ma, S and Hu, H}, title = {Ketamine blocks bursting in the lateral habenula to rapidly relieve depression.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {317-322}, pmid = {29446381}, issn = {1476-4687}, mesh = {Action Potentials/*drug effects ; Affect/drug effects ; Anhedonia/drug effects ; Animals ; Antidepressive Agents/administration & dosage/*pharmacology/*therapeutic use ; Calcium Channel Blockers/pharmacology/therapeutic use ; Calcium Channels/metabolism ; Depression/*drug therapy ; Disease Models, Animal ; Habenula/*drug effects/*metabolism/pathology/radiation effects ; Ketamine/administration & dosage/*pharmacology/*therapeutic use ; Male ; Mice ; Neurons/drug effects/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/antagonists & inhibitors/metabolism ; Reward ; Theta Rhythm/drug effects ; }, abstract = {The N-methyl-d-aspartate receptor (NMDAR) antagonist ketamine has attracted enormous interest in mental health research owing to its rapid antidepressant actions, but its mechanism of action has remained elusive. Here we show that blockade of NMDAR-dependent bursting activity in the 'anti-reward center', the lateral habenula (LHb), mediates the rapid antidepressant actions of ketamine in rat and mouse models of depression. LHb neurons show a significant increase in burst activity and theta-band synchronization in depressive-like animals, which is reversed by ketamine. Burst-evoking photostimulation of LHb drives behavioural despair and anhedonia. Pharmacology and modelling experiments reveal that LHb bursting requires both NMDARs and low-voltage-sensitive T-type calcium channels (T-VSCCs). Furthermore, local blockade of NMDAR or T-VSCCs in the LHb is sufficient to induce rapid antidepressant effects. Our results suggest a simple model whereby ketamine quickly elevates mood by blocking NMDAR-dependent bursting activity of LHb neurons to disinhibit downstream monoaminergic reward centres, and provide a framework for developing new rapid-acting antidepressants.}, } @article {pmid29446380, year = {2018}, author = {Kasahara, S and Miyoshi, Y and Yokota, S and Mitani, T and Kasahara, Y and Matsuda, S and Kumamoto, A and Matsuoka, A and Kazama, Y and Frey, HU and Angelopoulos, V and Kurita, S and Keika, K and Seki, K and Shinohara, I}, title = {Pulsating aurora from electron scattering by chorus waves.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {337-340}, pmid = {29446380}, issn = {1476-4687}, abstract = {Auroral substorms, dynamic phenomena that occur in the upper atmosphere at night, are caused by global reconfiguration of the magnetosphere, which releases stored solar wind energy. These storms are characterized by auroral brightening from dusk to midnight, followed by violent motions of distinct auroral arcs that suddenly break up, and the subsequent emergence of diffuse, pulsating auroral patches at dawn. Pulsating aurorae, which are quasiperiodic, blinking patches of light tens to hundreds of kilometres across, appear at altitudes of about 100 kilometres in the high-latitude regions of both hemispheres, and multiple patches often cover the entire sky. This auroral pulsation, with periods of several to tens of seconds, is generated by the intermittent precipitation of energetic electrons (several to tens of kiloelectronvolts) arriving from the magnetosphere and colliding with the atoms and molecules of the upper atmosphere. A possible cause of this precipitation is the interaction between magnetospheric electrons and electromagnetic waves called whistler-mode chorus waves. However, no direct observational evidence of this interaction has been obtained so far. Here we report that energetic electrons are scattered by chorus waves, resulting in their precipitation. Our observations were made in March 2017 with a magnetospheric spacecraft equipped with a high-angular-resolution electron sensor and electromagnetic field instruments. The measured quasiperiodic precipitating electron flux was sufficiently intense to generate a pulsating aurora, which was indeed simultaneously observed by a ground auroral imager.}, } @article {pmid29446379, year = {2018}, author = {Cui, Y and Yang, Y and Ni, Z and Dong, Y and Cai, G and Foncelle, A and Ma, S and Sang, K and Tang, S and Li, Y and Shen, Y and Berry, H and Wu, S and Hu, H}, title = {Astroglial Kir4.1 in the lateral habenula drives neuronal bursts in depression.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {323-327}, pmid = {29446379}, issn = {1476-4687}, mesh = {Action Potentials/drug effects ; Animals ; Astrocytes/drug effects/*metabolism ; Depression/drug therapy/*metabolism/pathology ; Habenula/drug effects/*metabolism/pathology ; Male ; Molecular Targeted Therapy ; Neurons/*metabolism ; Potassium Channels, Inwardly Rectifying/antagonists & inhibitors/*metabolism ; Rats ; Rats, Sprague-Dawley ; Reward ; }, abstract = {Enhanced bursting activity of neurons in the lateral habenula (LHb) is essential in driving depression-like behaviours, but the cause of this increase has been unknown. Here, using a high-throughput quantitative proteomic screen, we show that an astroglial potassium channel (Kir4.1) is upregulated in the LHb in rat models of depression. Kir4.1 in the LHb shows a distinct pattern of expression on astrocytic membrane processes that wrap tightly around the neuronal soma. Electrophysiology and modelling data show that the level of Kir4.1 on astrocytes tightly regulates the degree of membrane hyperpolarization and the amount of bursting activity of LHb neurons. Astrocyte-specific gain and loss of Kir4.1 in the LHb bidirectionally regulates neuronal bursting and depression-like symptoms. Together, these results show that a glia-neuron interaction at the perisomatic space of LHb is involved in setting the neuronal firing mode in models of a major psychiatric disease. Kir4.1 in the LHb might have potential as a target for treating clinical depression.}, } @article {pmid29446378, year = {2018}, author = {Guerra, RE and Kelleher, CP and Hollingsworth, AD and Chaikin, PM}, title = {Freezing on a sphere.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {346-350}, pmid = {29446378}, issn = {1476-4687}, mesh = {Capsid/chemistry ; *Crystallization ; *Freezing ; Hydrophobic and Hydrophilic Interactions ; *Microspheres ; *Models, Chemical ; Surface Properties ; }, abstract = {The best understood crystal ordering transition is that of two-dimensional freezing, which proceeds by the rapid eradication of lattice defects as the temperature is lowered below a critical threshold. But crystals that assemble on closed surfaces are required by topology to have a minimum number of lattice defects, called disclinations, that act as conserved topological charges-consider the 12 pentagons on a football or the 12 pentamers on a viral capsid. Moreover, crystals assembled on curved surfaces can spontaneously develop additional lattice defects to alleviate the stress imposed by the curvature. It is therefore unclear how crystallization can proceed on a sphere, the simplest curved surface on which it is impossible to eliminate such defects. Here we show that freezing on the surface of a sphere proceeds by the formation of a single, encompassing crystalline 'continent', which forces defects into 12 isolated 'seas' with the same icosahedral symmetry as footballs and viruses. We use this broken symmetry-aligning the vertices of an icosahedron with the defect seas and unfolding the faces onto a plane-to construct a new order parameter that reveals the underlying long-range orientational order of the lattice. The effects of geometry on crystallization could be taken into account in the design of nanometre- and micrometre-scale structures in which mobile defects are sequestered into self-ordered arrays. Our results may also be relevant in understanding the properties and occurrence of natural icosahedral structures such as viruses.}, } @article {pmid29446228, year = {2018}, author = {Nieuwenhuis, B and Haenzi, B and Andrews, MR and Verhaagen, J and Fawcett, JW}, title = {Integrins promote axonal regeneration after injury of the nervous system.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1339-1362}, pmid = {29446228}, issn = {1469-185X}, support = {G1000864//Medical Research Council/United Kingdom ; }, abstract = {Integrins are cell surface receptors that form the link between extracellular matrix molecules of the cell environment and internal cell signalling and the cytoskeleton. They are involved in several processes, e.g. adhesion and migration during development and repair. This review focuses on the role of integrins in axonal regeneration. Integrins participate in spontaneous axonal regeneration in the peripheral nervous system through binding to various ligands that either inhibit or enhance their activation and signalling. Integrin biology is more complex in the central nervous system. Integrins receptors are transported into growing axons during development, but selective polarised transport of integrins limits the regenerative response in adult neurons. Manipulation of integrins and related molecules to control their activation state and localisation within axons is a promising route towards stimulating effective regeneration in the central nervous system.}, } @article {pmid29446223, year = {2018}, author = {Helm, RR}, title = {Evolution and development of scyphozoan jellyfish.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1228-1250}, doi = {10.1111/brv.12393}, pmid = {29446223}, issn = {1469-185X}, abstract = {Scyphozoan jellyfish, or scyphomedusae, are conspicuous members of many ocean ecosystems, and have large impacts on human health and industry. Most scyphomedusae are the final stage in a complex life cycle that also includes two intermediate stages: the larval planula and benthic polyp. In species with all three life-cycle stages, the metamorphosis of a polyp into a juvenile scyphomedusa (ephyra) is termed strobilation, and polyps can produce one ephyra (termed monodisc strobilation) or many ephyrae (termed polydisc strobilation). In contrast to species with planula, polyp and medusa stages, a handful of scyphozoan species possess modified life cycles with reduced or absent stages. The evolutionary patterns associated with strobilation and life-cycle type have not been thoroughly investigated, and many studies of ephyra development and strobilation induction are not yet synthesized. Herein, I place the development of scyphomedusae in an evolutionary context. I first review the current evolutionary hypotheses for Scyphozoa. Next, I review what is known about scyphomedusa development across a broad diversity of species, including the first signs of strobilation, the formation of strobila segments, and the morphogenesis of ephyrae. I then review cases where the canonical scyphozoan life cycle has been modified, and take advantage of phylogenetic hypotheses to place these observations in an evolutionary context. I show that the evolution of monodisc strobilation occurred at least twice, and that the loss of intermediate life-cycle stages occurred several times independently; by contrast, the reduction of the medusa stage appears to have occurred within a single clade. I then briefly review the major natural cues of strobilation induction. Finally, I summarize what is currently known about the molecular mechanisms of strobilation induction and ephyra development. I conclude with suggestions for future directions in the field.}, } @article {pmid29446196, year = {2018}, author = {Maclean, HJ and Kristensen, TN and Sørensen, JG and Overgaard, J}, title = {Laboratory maintenance does not alter ecological and physiological patterns among species: a Drosophila case study.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {530-542}, doi = {10.1111/jeb.13241}, pmid = {29446196}, issn = {1420-9101}, abstract = {Large comparative studies in animal ecology, physiology and evolution often use animals reared in the laboratory for many generations; however, the relevance of these studies hinges on the assumption that laboratory populations are still representative for their wild living conspecifics. In this study, we investigate whether laboratory-maintained and freshly collected animal populations are fundamentally different and whether data from laboratory-maintained animals are valid to use in large comparative investigations of ecological and physiological patterns. Here, we obtained nine species of Drosophila with paired populations of laboratory-maintained and freshly collected flies. These species, representing a range of ecotypes, were assayed for four stress-tolerance, two body-size traits and six life-history traits. For all of these traits, we observed small differences in species-specific comparisons between field and laboratory populations; however, these differences were unsystematic and laboratory maintenance did not eclipse fundamental species characteristics. To investigate whether laboratory maintenance influence the general patterns in comparative studies, we correlated stress tolerance and life-history traits with environmental traits for the laboratory-maintained and freshly collected populations. Based on this analysis, we found that the comparative physiological and ecological trait correlations are similar irrespective of provenience. This finding is important for comparative biology in general because it validates comparative meta-analyses based on laboratory-maintained populations.}, } @article {pmid29444867, year = {2018}, author = {Engl, T and Kroiss, J and Kai, M and Nechitaylo, TY and Svatoš, A and Kaltenpoth, M}, title = {Evolutionary stability of antibiotic protection in a defensive symbiosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2020-E2029}, pmid = {29444867}, issn = {1091-6490}, mesh = {Animals ; Anti-Bacterial Agents/*chemistry ; Biological Assay ; Biological Evolution ; Ecology ; Fungi ; Indoles/*chemistry ; Microbial Sensitivity Tests ; Nigericin/*analogs & derivatives/chemistry ; Oxazoles/*chemistry ; Pyridines/*chemistry ; Species Specificity ; Streptomyces/*drug effects/metabolism ; *Symbiosis ; Wasps/*microbiology ; }, abstract = {The increasing resistance of human pathogens severely limits the efficacy of antibiotics in medicine, yet many animals, including solitary beewolf wasps, successfully engage in defensive alliances with antibiotic-producing bacteria for millions of years. Here, we report on the in situ production of 49 derivatives belonging to three antibiotic compound classes (45 piericidin derivatives, 3 streptochlorin derivatives, and nigericin) by the symbionts of 25 beewolf host species and subspecies, spanning 68 million years of evolution. Despite a high degree of qualitative stability in the antibiotic mixture, we found consistent quantitative differences between species and across geographic localities, presumably reflecting adaptations to combat local pathogen communities. Antimicrobial bioassays with the three main components and in silico predictions based on the structure and specificity in polyketide synthase domains of the piericidin biosynthesis gene cluster yield insights into the mechanistic basis and ecoevolutionary implications of producing a complex mixture of antimicrobial compounds in a natural setting.}, } @article {pmid29444866, year = {2018}, author = {Vanduffel, W}, title = {Long-term value memory in primates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1956-1958}, pmid = {29444866}, issn = {1091-6490}, mesh = {Animals ; *Memory, Long-Term ; Memory, Short-Term ; *Primates ; }, } @article {pmid29444865, year = {2018}, author = {Zeisig, BB and So, CWE}, title = {MLL-AF4, a double-edged sword for iPSC respecification into HSPCs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1964-1966}, pmid = {29444865}, issn = {1091-6490}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Histone-Lysine N-Methyltransferase ; *Myeloid-Lymphoid Leukemia Protein ; *Oncogene Proteins, Fusion ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; }, } @article {pmid29444864, year = {2018}, author = {Koide, Y and Ogino, A and Yoshikawa, T and Kitashima, Y and Saito, N and Kanaoka, Y and Onishi, K and Yoshitake, Y and Tsukiyama, T and Saito, H and Teraishi, M and Yamagata, Y and Uemura, A and Takagi, H and Hayashi, Y and Abe, T and Fukuta, Y and Okumoto, Y and Kanazawa, A}, title = {Lineage-specific gene acquisition or loss is involved in interspecific hybrid sterility in rice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1955-E1962}, pmid = {29444864}, issn = {1091-6490}, mesh = {Alleles ; Chromosome Mapping ; Chromosomes/ultrastructure ; *Crosses, Genetic ; Gene Deletion ; *Genes, Plant ; Heterozygote ; Hybridization, Genetic ; Mutagenesis ; Mutation ; Oryza/*genetics ; Phenotype ; Plant Infertility/*genetics ; Pollen/genetics ; Polymorphism, Genetic ; Protein Domains ; Reproduction/genetics ; }, abstract = {Understanding the genetic basis of reproductive barriers between species has been a central issue in evolutionary biology. The S1 locus in rice causes hybrid sterility and is a major reproductive barrier between two rice species, Oryza sativa and Oryza glaberrima The O. glaberrima-derived allele (denoted S1g) on the S1 locus causes preferential abortion of gametes with its allelic alternative (denoted S1s) in S1 g/S1 s heterozygotes. Here, we used mutagenesis and screening of fertile hybrid plants to isolate a mutant with an allele, S1 mut, which does not confer sterility in the S1 mut/S1 g and S1 mut/S1 s hybrids. We found that the causal mutation of the S1 mut allele was a deletion in the peptidase-coding gene (denoted "SSP") in the S1 locus of O. glaberrima No orthologous genes of SSP were found in the O. sativa genome. Transformation experiments indicated that the introduction of SSP in carriers of the S1 s allele did not induce sterility. In S1 mut/S1 s heterozygotes, the insertion of SSP led to sterility, suggesting that SSP complemented the loss of the functional phenotype of the mutant and that multiple factors are involved in the phenomenon. The polymorphisms caused by the lineage-specific acquisition or loss of the SSP gene were implicated in the generation of hybrid sterility. Our results demonstrated that artificial disruption of a single gene for the reproductive barrier creates a "neutral" allele, which facilitates interspecific hybridization for breeding programs.}, } @article {pmid29444863, year = {2018}, author = {Yuan, Y}, title = {Capturing bovine pluripotency.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1962-1963}, pmid = {29444863}, issn = {1091-6490}, mesh = {Animals ; Cattle ; Cell Differentiation ; *Embryonic Stem Cells ; *Pluripotent Stem Cells ; }, } @article {pmid29444862, year = {2018}, author = {Gallego-Bartolomé, J and Gardiner, J and Liu, W and Papikian, A and Ghoshal, B and Kuo, HY and Zhao, JM and Segal, DJ and Jacobsen, SE}, title = {Targeted DNA demethylation of the Arabidopsis genome using the human TET1 catalytic domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2125-E2134}, pmid = {29444862}, issn = {1091-6490}, support = {R21 CA204563/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/*genetics ; Arabidopsis Proteins/metabolism ; Catalytic Domain ; *DNA Methylation ; DNA Transposable Elements ; DNA, Plant/chemistry ; Epigenesis, Genetic ; Flowers ; Gene Expression Regulation, Plant ; Gene Silencing ; *Genome, Plant ; Homeodomain Proteins/metabolism ; Humans ; Mixed Function Oxygenases/*chemistry ; Mutation ; Promoter Regions, Genetic ; Proto-Oncogene Proteins/*chemistry ; Transcription Factors/metabolism ; Zinc Fingers ; }, abstract = {DNA methylation is an important epigenetic modification involved in gene regulation and transposable element silencing. Changes in DNA methylation can be heritable and, thus, can lead to the formation of stable epialleles. A well-characterized example of a stable epiallele in plants is fwa, which consists of the loss of DNA cytosine methylation (5mC) in the promoter of the FLOWERING WAGENINGEN (FWA) gene, causing up-regulation of FWA and a heritable late-flowering phenotype. Here we demonstrate that a fusion between the catalytic domain of the human demethylase TEN-ELEVEN TRANSLOCATION1 (TET1cd) and an artificial zinc finger (ZF) designed to target the FWA promoter can cause highly efficient targeted demethylation, FWA up-regulation, and a heritable late-flowering phenotype. Additional ZF-TET1cd fusions designed to target methylated regions of the CACTA1 transposon also caused targeted demethylation and changes in expression. Finally, we have developed a CRISPR/dCas9-based targeted demethylation system using the TET1cd and a modified SunTag system. Similar to the ZF-TET1cd fusions, the SunTag-TET1cd system is able to target demethylation and activate gene expression when directed to the FWA or CACTA1 loci. Our study provides tools for targeted removal of 5mC at specific loci in the genome with high specificity and minimal off-target effects. These tools provide the opportunity to develop new epialleles for traits of interest, and to reactivate expression of previously silenced genes, transgenes, or transposons.}, } @article {pmid29444861, year = {2018}, author = {Lee, KH and Sulbarán, G and Yang, S and Mun, JY and Alamo, L and Pinto, A and Sato, O and Ikebe, M and Liu, X and Korn, ED and Sarsoza, F and Bernstein, SI and Padrón, R and Craig, R}, title = {Interacting-heads motif has been conserved as a mechanism of myosin II inhibition since before the origin of animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1991-E2000}, pmid = {29444861}, issn = {1091-6490}, support = {R01 AR034711/AR/NIAMS NIH HHS/United States ; R37 GM032443/GM/NIGMS NIH HHS/United States ; R01 AR072036/AR/NIAMS NIH HHS/United States ; R01 GM032443/GM/NIGMS NIH HHS/United States ; R01 AR067279/AR/NIAMS NIH HHS/United States ; R01 HL073050/HL/NHLBI NIH HHS/United States ; R01 AR062279/AR/NIAMS NIH HHS/United States ; R01 HL111696/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Actins/chemistry ; Adenosine Triphosphate/chemistry ; Amino Acid Motifs ; Animals ; Biological Evolution ; Calcium/chemistry ; Cell Line ; Computational Biology ; Cryoelectron Microscopy ; Dictyostelium ; Image Processing, Computer-Assisted ; Insecta ; Microscopy, Electron ; Myosin Type II/*antagonists & inhibitors/chemistry ; Phosphorylation ; Porifera ; Protein Binding ; Schizosaccharomyces ; Scyphozoa ; Sea Anemones ; Turkeys ; }, abstract = {Electron microscope studies have shown that the switched-off state of myosin II in muscle involves intramolecular interaction between the two heads of myosin and between one head and the tail. The interaction, seen in both myosin filaments and isolated molecules, inhibits activity by blocking actin-binding and ATPase sites on myosin. This interacting-heads motif is highly conserved, occurring in invertebrates and vertebrates, in striated, smooth, and nonmuscle myosin IIs, and in myosins regulated by both Ca2+ binding and regulatory light-chain phosphorylation. Our goal was to determine how early this motif arose by studying the structure of inhibited myosin II molecules from primitive animals and from earlier, unicellular species that predate animals. Myosin II from Cnidaria (sea anemones, jellyfish), the most primitive animals with muscles, and Porifera (sponges), the most primitive of all animals (lacking muscle tissue) showed the same interacting-heads structure as myosins from higher animals, confirming the early origin of the motif. The social amoeba Dictyostelium discoideum showed a similar, but modified, version of the motif, while the amoeba Acanthamoeba castellanii and fission yeast (Schizosaccharomyces pombe) showed no head-head interaction, consistent with the different sequences and regulatory mechanisms of these myosins compared with animal myosin IIs. Our results suggest that head-head/head-tail interactions have been conserved, with slight modifications, as a mechanism for regulating myosin II activity from the emergence of the first animals and before. The early origins of these interactions highlight their importance in generating the inhibited (relaxed) state of myosin in muscle and nonmuscle cells.}, } @article {pmid29444860, year = {2018}, author = {Hoppe, D and Helfmann, S and Rothkopf, CA}, title = {Humans quickly learn to blink strategically in response to environmental task demands.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2246-2251}, pmid = {29444860}, issn = {1091-6490}, mesh = {Adult ; Behavior/*physiology ; Blinking/*physiology ; Computer Simulation ; *Environment ; Female ; Humans ; Male ; Middle Aged ; Models, Biological ; Normal Distribution ; Probability ; Saccades/*physiology ; Vision, Ocular/*physiology ; Young Adult ; }, abstract = {Eye blinking is one of the most frequent human actions. The control of blinking is thought to reflect complex interactions between maintaining clear and healthy vision and influences tied to central dopaminergic functions including cognitive states, psychological factors, and medical conditions. The most imminent consequence of blinking is a temporary loss of vision. Minimizing this loss of information is a prominent explanation for changes in blink rates and temporarily suppressed blinks, but quantifying this loss is difficult, as environmental regularities are usually complex and unknown. Here we used a controlled detection experiment with parametrically generated event statistics to investigate human blinking control. Subjects were able to learn environmental regularities and adapted their blinking behavior strategically to better detect future events. Crucially, our design enabled us to develop a computational model that allows quantifying the consequence of blinking in terms of task performance. The model formalizes ideas from active perception by describing blinking in terms of optimal control in trading off intrinsic costs for blink suppression with task-related costs for missing an event under perceptual uncertainty. Remarkably, this model not only is sufficient to reproduce key characteristics of the observed blinking behavior such as blink suppression and blink compensation but also predicts without further assumptions the well-known and diverse distributions of time intervals between blinks, for which an explanation has long been elusive.}, } @article {pmid29444859, year = {2018}, author = {Kaznatcheev, A}, title = {Effective games and the confusion over spatial structure.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1709}, pmid = {29444859}, issn = {1091-6490}, } @article {pmid29444858, year = {2018}, author = {Rasouly, A and Nudler, E}, title = {Antibiotic killing through oxidized nucleotides.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1967-1969}, pmid = {29444858}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Anti-Bacterial Agents ; *Nucleotides ; Oxidation-Reduction ; }, } @article {pmid29444857, year = {2018}, author = {Su, NQ and Zhu, Z and Xu, X}, title = {Doubly hybrid density functionals that correctly describe both density and energy for atoms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2287-2292}, pmid = {29444857}, issn = {1091-6490}, abstract = {Recently, it was argued [Medvedev MG, et al. (2017) Science 355:49-52] that the development of density functional approximations (DFAs) is "straying from the path toward the exact functional." The exact functional should yield both exact energy and density for a system of interest; nevertheless, they found that many heavily fitted functionals for molecular energies actually lead to poor electron densities of atoms. They also observed a trend that, for the nonempirical and few-parameter functionals, densities can be improved as one climbs up the first four rungs of the Jacob's ladder of DFAs. The XYG3 type of doubly hybrid functionals (xDHs) represents a less-empirical and fewer-parameter functional on the top fifth rung, in which both the Hartree-Fock-like exchange and the second-order perturbative (MP2-like) correlation are hybridized with the low rung functionals. Here, we show that xDHs can well describe both density and energy for the same atomic set of Medvedev et al., showing that the latter trend can well be extended to the top fifth rung.}, } @article {pmid29444856, year = {2018}, author = {Markovic, S and Fages, A and Roussel, T and Hadas, R and Brandis, A and Neeman, M and Frydman, L}, title = {Placental physiology monitored by hyperpolarized dynamic 13C magnetic resonance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2429-E2436}, pmid = {29444856}, issn = {1091-6490}, support = {R01 HD086323/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Bicarbonates/metabolism ; Carbon Isotopes/chemistry ; Disease Models, Animal ; Female ; Humans ; Lactic Acid/metabolism ; Magnetic Resonance Imaging/*methods ; Male ; Monitoring, Physiologic ; Placenta/diagnostic imaging/*physiology ; Pre-Eclampsia/diagnosis/*diagnostic imaging/metabolism ; Pregnancy ; Pyruvic Acid/chemistry/metabolism ; Rats ; Rats, Wistar ; }, abstract = {Placental functions, including transport and metabolism, play essential roles in pregnancy. This study assesses such processes in vivo, from a hyperpolarized MRI perspective. Hyperpolarized urea, bicarbonate, and pyruvate were administered to near-term pregnant rats, and all metabolites displayed distinctive behaviors. Little evidence of placental barrier crossing was observed for bicarbonate, at least within the timescales allowed by 13C relaxation. By contrast, urea was observed to cross the placental barrier, with signatures visible from certain fetal organs including the liver. This was further evidenced by the slower decay times observed for urea in placentas vis-à-vis other maternal compartments and validated by mass spectrometric analyses. A clear placental localization, as well as concurrent generation of hyperpolarized lactate, could also be detected for [1-13C]pyruvate. These metabolites also exhibited longer lifetimes in the placentas than in maternal arteries, consistent with a metabolic activity occurring past the trophoblastic interface. When extended to a model involving the administration of a preeclampsia-causing chemical, hyperpolarized MR revealed changes in urea's transport, as well as decreases in placental glycolysis vs. the naïve animals. These distinct behaviors highlight the potential of hyperpolarized MR for the early, minimally invasive detection of aberrant placental metabolism.}, } @article {pmid29444855, year = {2018}, author = {Kerstholt, M and Vrijmoeth, H and Lachmandas, E and Oosting, M and Lupse, M and Flonta, M and Dinarello, CA and Netea, MG and Joosten, LAB}, title = {Role of glutathione metabolism in host defense against Borrelia burgdorferi infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2320-E2328}, pmid = {29444855}, issn = {1091-6490}, support = {R01 AI015614/AI/NIAID NIH HHS/United States ; }, mesh = {Borrelia burgdorferi/*physiology ; Cytokines/genetics/metabolism ; Glutathione/*metabolism ; Host-Pathogen Interactions ; Humans ; Lyme Disease/genetics/*metabolism/microbiology ; Monocytes/metabolism ; Reactive Oxygen Species/metabolism ; }, abstract = {Pathogen-induced changes in host cell metabolism are known to be important for the immune response. In this study, we investigated how infection with the Lyme disease-causing bacterium Borrelia burgdorferi (Bb) affects host metabolic pathways and how these metabolic pathways may impact host defense. First, metabolome analysis was performed on human primary monocytes from healthy volunteers, stimulated for 24 h with Bb at low multiplicity of infection (MOI). Pathway analysis indicated that glutathione (GSH) metabolism was the pathway most significantly affected by Bb Specifically, intracellular levels of GSH increased on average 10-fold in response to Bb exposure. Furthermore, these changes were found to be specific, as they were not seen during stimulation with other pathogens. Next, metabolome analysis was performed on serum samples from patients with early-onset Lyme disease in comparison with patients with other infections. Supporting the in vitro analysis, we identified a cluster of GSH-related metabolites, the γ-glutamyl amino acids, specifically altered in patients with Lyme disease, and not in other infections. Lastly, we performed in vitro experiments to validate the role for GSH metabolism in host response against Bb. We found that the GSH pathway is essential for Bb-induced cytokine production and identified glutathionylation as a potential mediating mechanism. Taken together, these data indicate a central role for the GSH pathway in the host response to Bb GSH metabolism and glutathionylation may therefore be important factors in the pathogenesis of Lyme disease and potentially other inflammatory diseases as well.}, } @article {pmid29444854, year = {2018}, author = {Brown, JD and Feldman, ZB and Doherty, SP and Reyes, JM and Rahl, PB and Lin, CY and Sheng, Q and Duan, Q and Federation, AJ and Kung, AL and Haldar, SM and Young, RA and Plutzky, J and Bradner, JE}, title = {BET bromodomain proteins regulate enhancer function during adipogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2144-2149}, pmid = {29444854}, issn = {1091-6490}, support = {P01 HL048743/HL/NHLBI NIH HHS/United States ; R01 HL133665/HL/NHLBI NIH HHS/United States ; R01 DK107239/DK/NIDDK NIH HHS/United States ; K08 HL105678/HL/NHLBI NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; T32 GM008307/GM/NIGMS NIH HHS/United States ; R56 HL125894/HL/NHLBI NIH HHS/United States ; }, mesh = {Adipocytes/*physiology ; Adipogenesis ; Adipose Tissue/*cytology/physiology ; Animals ; Cell Differentiation ; Gene Expression Regulation/*physiology ; Male ; Mice ; Nuclear Proteins/*metabolism ; Transcription Factors/*metabolism ; }, abstract = {Developmental transitions are guided by master regulatory transcription factors. During adipogenesis, a transcriptional cascade culminates in the expression of PPARγ and C/EBPα, which orchestrate activation of the adipocyte gene expression program. However, the coactivators controlling PPARγ and C/EBPα expression are less well characterized. Here, we show the bromodomain-containing protein, BRD4, regulates transcription of PPARγ and C/EBPα. Analysis of BRD4 chromatin occupancy reveals that induction of adipogenesis in 3T3L1 fibroblasts provokes dynamic redistribution of BRD4 to de novo super-enhancers proximal to genes controlling adipocyte differentiation. Inhibition of the bromodomain and extraterminal domain (BET) family of bromodomain-containing proteins impedes BRD4 occupancy at these de novo enhancers and disrupts transcription of Pparg and Cebpa, thereby blocking adipogenesis. Furthermore, silencing of these BRD4-occupied distal regulatory elements at the Pparg locus by CRISPRi demonstrates a critical role for these enhancers in the control of Pparg gene expression and adipogenesis in 3T3L1s. Together, these data establish BET bromodomain proteins as time- and context-dependent coactivators of the adipocyte cell state transition.}, } @article {pmid29444851, year = {2018}, author = {Callier, V}, title = {Inner Workings: How the butterfly got its spots (and why it matters).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1397-1399}, pmid = {29444851}, issn = {1091-6490}, mesh = {Animals ; Butterflies/genetics/*physiology ; Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Regulatory Networks ; Insect Proteins/genetics ; Pigmentation ; Wings, Animal/*physiology ; }, } @article {pmid29444714, year = {2018}, author = {Adehin, A and Bolaji, OO}, title = {Thiopurine S-methyltransferase activity in Nigerians: phenotypes and activity reference values.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {129}, pmid = {29444714}, issn = {1756-0500}, mesh = {Adult ; Female ; Genotype ; Humans ; Male ; Methyltransferases/*blood ; Nigeria ; Phenotype ; Reference Values ; Young Adult ; }, abstract = {OBJECTIVES: This study assessed the activity of thiopurine S-methyltransferase (TPMT) in Nigerians with a view to providing data on susceptibility to thiopurine toxicity, and as well generate reference activity values for clinical use.

RESULTS: TPMT activity, expressed as the amount of 6MMP in ng/mL after 1 h incubation at 37 °C per haemoglobin (U/g Hb), varied between 2.34 and 63.50 U/g Hb in the study population. Poor metabolic phenotypes, characterised by an activity values below 8.41 U/g Hb, were observed in 20% of the study subjects. Intermediate metabolizers had activity values between 8.41 and 16.13 U/g Hb. Fast and very fast metabolizers were characterised by activity values of 16.20-56.22 and > 56.22 U/g Hb, respectively. These findings suggest that a potentially huge discordance between TPMT phenotype and genotype exist in Nigerians, and emphasizes the superiority of a prior determination of TPMT metabolic phenotype in ensuring the safety of thiopurine drug administration in the population.}, } @article {pmid29444708, year = {2018}, author = {Imaizumi, S and Tanno, Y}, title = {Rasch analysis of the Trypophobia Questionnaire.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {128}, pmid = {29444708}, issn = {1756-0500}, support = {16J00411//Japan Society for the Promotion of Science/ ; 17K12701//Japan Society for the Promotion of Science/ ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Female ; Humans ; Male ; Middle Aged ; *Pattern Recognition, Visual/physiology ; Phobic Disorders/*diagnosis/physiopathology ; Psychometrics/*instrumentation ; Surveys and Questionnaires/*standards ; Young Adult ; }, abstract = {OBJECTIVE: This study aimed to assess Rasch-based psychometric properties of the Trypophobia Questionnaire measuring proneness to trypophobia, which refers to disgust and unpleasantness induced by the observation of clusters of objects (e.g., lotus seed pods).

RESULTS: Rasch analysis was performed on data from 582 healthy Japanese adults. The results suggested that Trypophobia Questionnaire has a unidimensional structure with ordered response categories and sufficient person and item reliabilities, and that it does not have differential item functioning across sexes and age groups, whereas the targeting of the scale leaves room for improvements. When items that did not fit the Rasch model were removed, the shortened version showed slightly improved psychometric properties. However, results were not conclusive in determining whether the full or shortened version is better for practical use. Further assessment and validation are needed.}, } @article {pmid29444701, year = {2018}, author = {Jayaweera, JAAS and Noordeen, F and Kothalaweala, S and Pitchai, FNN and Rayes, MLM}, title = {A case series on common cold to severe bronchiolitis and pneumonia in children following human metapneumovirus infection in Sri Lanka.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {127}, pmid = {29444701}, issn = {1756-0500}, support = {(UGC/2012/JAAS Jayaweera//University Grant Commission Sri Lanka/ ; RG/AF/2013/38/M//University of Peradeniya Sri Lanka/ ; }, mesh = {Bronchiolitis/diagnosis/*epidemiology/virology ; Child, Preschool ; Coinfection/diagnosis/*epidemiology/virology ; Common Cold/diagnosis/*epidemiology/virology ; Comorbidity ; Female ; Humans ; Infant ; Male ; Metapneumovirus/isolation & purification/*pathogenicity ; Paramyxoviridae Infections/diagnosis/*epidemiology/virology ; Pneumonia/diagnosis/*epidemiology/virology ; Prevalence ; Respiratory Syncytial Virus, Human/isolation & purification/*pathogenicity ; Severity of Illness Index ; Sri Lanka/epidemiology ; }, abstract = {OBJECTIVES: The prevalence of hMPV infections in Sri Lanka has not been reported and here we report a case series of hMPV infection in children less than 5 years. Patients with ARTI were included from Teaching Hospital, Anuradhapura from March 2013 to August 2014. Indirect fluorescence assay was performed on nasopharyngeal aspirates for the identification of respiratory viruses [respiratory syncytial virus (RSV), parainfluenza virus 1, 2 and 3, influenza A and B and hMPV]. Moreover, reverse transcriptase-polymerase chain reaction was done to further confirm the hMPV infection.

RESULTS: In this case series, hMPV infection showed a range of respiratory symptoms from common cold to life threatening lower respiratory tract infections with varying severity. In some cases, the clinical presentation of hMPV infection was similar to the ARTI caused by RSV. hMPV co-infections with of RSV have also been seen in some cases of ARTI. A child delivered through cesarean section and birth order > 3 has an Odds ratio of 3.5 and 4.3 (95% CI) for developing co-infection with RSV compared to hMPV mono-infections. Lack of diagnostic facilities to identify the viral aetiology has contributed to the use of antibiotics indicating the need for establishing viral diagnostic facilities in the country.}, } @article {pmid29444697, year = {2018}, author = {Luna, ACL and Santos Filho, JRA and Hesse, H and Neto, SC and Chierice, GO and Maria, DA}, title = {Modulation of pro-apoptotic effects and mitochondrial potential on B16F10 cells by DODAC/PHO-S liposomes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {126}, pmid = {29444697}, issn = {1756-0500}, support = {2015/02950- 1.//Sao Paulo Research Foundation/ ; }, mesh = {Adjuvants, Immunologic/*pharmacology ; Animals ; Apoptosis/*drug effects ; Cell Line, Tumor ; Cytotoxins/*pharmacology ; Ethanolamines/*pharmacology ; Liposomes/*pharmacology ; Melanoma, Experimental/*drug therapy ; Mice ; Mitochondria/*drug effects ; Nanotechnology ; Quaternary Ammonium Compounds/*pharmacology ; }, abstract = {OBJECTIVE: We aimed to evaluate the potential of DODAC/PHO-S liposomes on the modulation of the expression of pro-apoptotic proteins, loss of lysosomal integrity and the mitochondrial electrical potential, compared with phosphoethanolamine.

RESULTS: The results of this study demonstrate that DODAC/PHO-S liposomes have exhibited broad cytotoxic potential in B16F10 murine melanoma cells, with significantly greater proportions than treatment with PHO-S. The treatment with the DODAC/PHO-S 2.0 mM liposomal formulation was more efficient in decreasing mitochondrial electrical potential at the same concentrations and treatment time than PHO-S The liposomal formulation DODAC/PHO-S (2.0 mM) was more efficient to promote morphological changes in the cells, without presenting intact lysosomes, at the same time of treatment and concentration as PHO-S Our results demonstrated that the liposomal formulation increased DR4 receptor expression and activated caspases 8 and 3, resulting in the release of cytochrome c in B16F10 tumour cells, when compared to treatment with PHO-S The data obtained prove that the use of DODAC as carrier can maximize the cytotoxic effects of PHO-S This was demonstrated by the translocation of cytochrome c to the cytoplasm and activation of caspase-3 and 8, decreasing the mitochondrial electrical potential and generating morphological changes, in B16F10 cells.}, } @article {pmid29444662, year = {2018}, author = {Gao, T and Shu, J and Cui, J}, title = {A systematic approach to RNA-associated motif discovery.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {146}, pmid = {29444662}, issn = {1471-2164}, support = {1P20GM104320/NH/NIH HHS/United States ; Food for Health Seed Grant//University of Nebraska-Lincoln (US)/International ; }, mesh = {Base Sequence ; Binding Sites/genetics ; Cell Line, Tumor ; Computational Biology/*methods ; Exosomes/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Internet ; MicroRNAs/genetics/metabolism ; Nucleotide Motifs/*genetics ; RNA, Messenger/genetics/metabolism ; Reproducibility of Results ; }, abstract = {BACKGROUND: Sequencing-based large screening of RNA-protein and RNA-RNA interactions has enabled the mechanistic study of post-transcriptional RNA processing and sorting, including exosome-mediated RNA secretion. The downstream analysis of RNA binding sites has encouraged the investigation of novel sequence motifs, which resulted in exceptional new challenges for identifying motifs from very short sequences (e.g., small non-coding RNAs or truncated messenger RNAs), where conventional methods tend to be ineffective. To address these challenges, we propose a novel motif-finding method and validate it on a wide range of RNA applications.

RESULTS: We first perform motif analysis on microRNAs and longer RNA fragments from various cellular and exosomal sources, and then validate our prediction through literature search and experimental test. For example, a 4 bp-long motif, GUUG, was detected to be responsible for microRNA loading in exosomes involved in human colon cancer (SW620). Additional performance comparisons in various case studies have shown that this new approach outperforms several existing state-of-the-art methods in detecting motifs with exceptional high coverage and explicitness.

CONCLUSIONS: In this work, we have demonstrated the promising performance of a new motif discovery approach that is particularly effective in current RNA applications. Important discoveries resulting from this work include the identification of possible RNA-loading motifs in a variety of exosomes, as well as novel insights in sequence features of RNA cargos, i.e., short non-coding RNAs and messenger RNAs may share similar loading mechanism into exosomes. This method has been implemented and deployed as a new webserver named MDS2 which is accessible at http://sbbi-panda.unl.edu/MDS2/ , along with a standalone package available for download at https://github.com/sbbi/MDS2 .}, } @article {pmid29444661, year = {2018}, author = {Zhou, Q and Su, X and Jing, G and Chen, S and Ning, K}, title = {RNA-QC-chain: comprehensive and fast quality control for RNA-Seq data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {144}, pmid = {29444661}, issn = {1471-2164}, support = {No. 2016RC-YJ01//Chinese Academy of Fishery Sciences/International ; 31401076//National Natural Science Foundation of China/International ; 31771463//National Natural Science Foundation of China/International ; 31671374//National Natural Science Foundation of China/International ; ZR2017ZB0421//Shandong Provincial Natural Science Foundation, China/International ; }, mesh = {Animals ; Computational Biology/*methods ; High-Throughput Nucleotide Sequencing/methods/standards ; Humans ; Internet ; Quality Control ; RNA/chemistry/*genetics ; Reproducibility of Results ; *Software ; }, abstract = {BACKGROUND: RNA-Seq has become one of the most widely used applications based on next-generation sequencing technology. However, raw RNA-Seq data may have quality issues, which can significantly distort analytical results and lead to erroneous conclusions. Therefore, the raw data must be subjected to vigorous quality control (QC) procedures before downstream analysis. Currently, an accurate and complete QC of RNA-Seq data requires of a suite of different QC tools used consecutively, which is inefficient in terms of usability, running time, file usage, and interpretability of the results.

RESULTS: We developed a comprehensive, fast and easy-to-use QC pipeline for RNA-Seq data, RNA-QC-Chain, which involves three steps: (1) sequencing-quality assessment and trimming; (2) internal (ribosomal RNAs) and external (reads from foreign species) contamination filtering; (3) alignment statistics reporting (such as read number, alignment coverage, sequencing depth and pair-end read mapping information). This package was developed based on our previously reported tool for general QC of next-generation sequencing (NGS) data called QC-Chain, with extensions specifically designed for RNA-Seq data. It has several features that are not available yet in other QC tools for RNA-Seq data, such as RNA sequence trimming, automatic rRNA detection and automatic contaminating species identification. The three QC steps can run either sequentially or independently, enabling RNA-QC-Chain as a comprehensive package with high flexibility and usability. Moreover, parallel computing and optimizations are embedded in most of the QC procedures, providing a superior efficiency. The performance of RNA-QC-Chain has been evaluated with different types of datasets, including an in-house sequencing data, a semi-simulated data, and two real datasets downloaded from public database. Comparisons of RNA-QC-Chain with other QC tools have manifested its superiorities in both function versatility and processing speed.

CONCLUSIONS: We present here a tool, RNA-QC-Chain, which can be used to comprehensively resolve the quality control processes of RNA-Seq data effectively and efficiently.}, } @article {pmid29444641, year = {2018}, author = {Rahman, RU and Gautam, A and Bethune, J and Sattar, A and Fiosins, M and Magruder, DS and Capece, V and Shomroni, O and Bonn, S}, title = {Oasis 2: improved online analysis of small RNA-seq data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {54}, pmid = {29444641}, issn = {1471-2105}, mesh = {Base Sequence ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing ; MicroRNAs/genetics ; RNA, Small Untranslated/*genetics ; Sequence Analysis, RNA/*methods ; Software ; Statistics as Topic/*methods ; }, abstract = {BACKGROUND: Small RNA molecules play important roles in many biological processes and their dysregulation or dysfunction can cause disease. The current method of choice for genome-wide sRNA expression profiling is deep sequencing.

RESULTS: Here we present Oasis 2, which is a new main release of the Oasis web application for the detection, differential expression, and classification of small RNAs in deep sequencing data. Compared to its predecessor Oasis, Oasis 2 features a novel and speed-optimized sRNA detection module that supports the identification of small RNAs in any organism with higher accuracy. Next to the improved detection of small RNAs in a target organism, the software now also recognizes potential cross-species miRNAs and viral and bacterial sRNAs in infected samples. In addition, novel miRNAs can now be queried and visualized interactively, providing essential information for over 700 high-quality miRNA predictions across 14 organisms. Robust biomarker signatures can now be obtained using the novel enhanced classification module.

CONCLUSIONS: Oasis 2 enables biologists and medical researchers to rapidly analyze and query small RNA deep sequencing data with improved precision, recall, and speed, in an interactive and user-friendly environment.

Oasis 2 is implemented in Java, J2EE, mysql, Python, R, PHP and JavaScript. It is freely available at https://oasis.dzne.de.}, } @article {pmid29444639, year = {2018}, author = {Cardoso, TF and Quintanilla, R and Castelló, A and González-Prendes, R and Amills, M and Cánovas, Á}, title = {Differential expression of mRNA isoforms in the skeletal muscle of pigs with distinct growth and fatness profiles.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {145}, pmid = {29444639}, issn = {1471-2164}, support = {AGL2013-48742-C2-1-R//Spanish Ministry of Economy and Competitivity/International ; AGL2013-48742-C2-2-R//Spanish Ministry of Economy and Competitivity/International ; 2014 SGR 1528//Agency for Management of University and Research Grants of the Generalitat de Catalunya/International ; FPU12/00860//FPU Ph.D. grant from the Spanish Ministry of Education/International ; SEV-2015-0533//Spanish Ministry of Economy and Competitivity/International ; }, mesh = {Adipose Tissue/growth & development/*metabolism ; Animals ; Annexin A2/genetics ; Antigens, CD/genetics ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Integrin alpha6/genetics ; Muscle, Skeletal/growth & development/*metabolism ; Obesity/genetics ; RNA Isoforms/*genetics ; Semaphorins/genetics ; Swine ; Tissue Inhibitor of Metalloproteinase-1/genetics ; }, abstract = {BACKGROUND: The identification of genes differentially expressed in the skeletal muscle of pigs displaying distinct growth and fatness profiles might contribute to identify the genetic factors that influence the phenotypic variation of such traits. So far, the majority of porcine transcriptomic studies have investigated differences in gene expression at a global scale rather than at the mRNA isoform level. In the current work, we have investigated the differential expression of mRNA isoforms in the gluteus medius (GM) muscle of 52 Duroc HIGH (increased backfat thickness, intramuscular fat and saturated and monounsaturated fatty acids contents) and LOW pigs (opposite phenotype, with an increased polyunsaturated fatty acids content).

RESULTS: Our analysis revealed that 10.9% of genes expressed in the GM muscle generate alternative mRNA isoforms, with an average of 2.9 transcripts per gene. By using two different pipelines, one based on the CLC Genomics Workbench and another one on the STAR, RSEM and DESeq2 softwares, we have identified 10 mRNA isoforms that both pipelines categorize as differentially expressed in HIGH vs LOW pigs (P-value < 0.01 and ±0.6 log2fold-change). Only five mRNA isoforms, produced by the ITGA5, SEMA4D, LITAF, TIMP1 and ANXA2 genes, remain significant after correction for multiple testing (q-value < 0.05 and ±0.6 log2fold-change), being upregulated in HIGH pigs.

CONCLUSIONS: The increased levels of specific ITGA5, LITAF, TIMP1 and ANXA2 mRNA isoforms in HIGH pigs is consistent with reports indicating that the overexpression of these four genes is associated with obesity and metabolic disorders in humans. A broader knowledge about the functional attributes of these mRNA variants would be fundamental to elucidate the consequences of transcript diversity on the determinism of porcine phenotypes of economic interest.}, } @article {pmid29444636, year = {2018}, author = {He, B and Hu, Z and Ma, L and Li, H and Ai, M and Han, J and Zeng, B}, title = {Transcriptome analysis of different growth stages of Aspergillus oryzae reveals dynamic changes of distinct classes of genes during growth.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {12}, pmid = {29444636}, issn = {1471-2180}, support = {31460447//NSFC/International ; 3000035402//General Science and Technology Project of Nanchang City/International ; 20114BAB205039, 20171BAB214004//the Science Funds of Natural Science Foundation of Jiangxi Province/International ; XJ17B09//Doctor and master specific projects of Honghe University/International ; 2016PY068//the project of young and middle-aged talent of Yunnan province/International ; GJJ160765, GJJ160795 and GJJ160794//Science and Technology Research Project of Jiangxi Provincial Department of Education/International ; }, mesh = {Aspergillus oryzae/*genetics/*growth & development/metabolism ; *Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Fungal/genetics ; Gene Ontology ; Genes, Fungal/genetics ; High-Throughput Nucleotide Sequencing ; Metabolic Networks and Pathways ; Morphogenesis/*genetics/*physiology ; Multigene Family ; RNA, Messenger/genetics ; Transcriptome ; }, abstract = {BACKGROUND: The gene expression profile and metabolic pathways of Aspergillus oryzae underlying the anatomical and morphological differentiation across different growth stages have not been fully characterized. The rapid development of next-generation sequencing technologies provides advanced knowledge of the genomic organization of A. oryzae.

RESULTS: In this study, we characterized the growth and development of A. oryzae at different growth stages, including the adaptive phase, logarithmic phase, and stationary phase. Our results revealed that A. oryzae undergoes physiological and morphological differentiation across the different stages. RNA-seq was employed to analyze the three stages of A. oryzae, which generated more than 27 million high-quality reads per sample. The analysis of differential gene expression showed more genes expressed differentially upon transition from the adaptive phase to the logarithmic and stationary phases, while relatively steady trend was observed during the transition from the logarithmic phase to the stationary phase. GO classification of the differentially expressed genes among different growth stages revealed that most of these genes were enriched for single-organism process, metabolic process, and catalytic activity. These genes were then subjected to a clustering analysis. The results showed that the cluster with the majority of genes with increased expression upon transition from the adaptive phase to the logarithmic phase, and steady expression from the logarithmic phase to the stationary phase was mainly involved in the carbohydrate and amino acid metabolism.

CONCLUSION: Our results provide a foundation for identifying developmentally important genes and understanding the biological processes across various growth stages.}, } @article {pmid29444635, year = {2018}, author = {Weiss, J and Terry, MI and Martos-Fuentes, M and Letourneux, L and Ruiz-Hernández, V and Fernández, JA and Egea-Cortines, M}, title = {Diel pattern of circadian clock and storage protein gene expression in leaves and during seed filling in cowpea (Vigna unguiculata).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {33}, pmid = {29444635}, issn = {1471-2229}, support = {FP7-613781//FP7 Food, Agriculture and Fisheries, Biotechnology/ ; }, mesh = {Circadian Clocks/genetics/*physiology ; Gene Expression Regulation, Plant/genetics/physiology ; Plant Leaves/*metabolism/*physiology ; Plant Proteins/genetics/*metabolism ; Seeds/*metabolism/*physiology ; Vigna/*metabolism/*physiology ; }, abstract = {BACKGROUND: Cowpea (Vigna unguiculata) is an important source of protein supply for animal and human nutrition. The major storage globulins VICILIN and LEGUMIN (LEG) are synthesized from several genes including LEGA, LEGB, LEGJ and CVC (CONVICILIN). The current hypothesis is that the plant circadian core clock genes are conserved in a wide array of species and that primary metabolism is to a large extent controlled by the plant circadian clock. Our aim was to investigate a possible link between gene expression of storage proteins and the circadian clock.

RESULTS: We identified cowpea orthologues of the core clock genes VunLHY, VunTOC1, VunGI and VunELF3, the protein storage genes VunLEG, VunLEGJ, and VunCVC as well as nine candidate reference genes used in RT-PCR. ELONGATION FACTOR 1-A (ELF1A) resulted the most suitable reference gene. The clock genes VunELF3, VunGI, VunTOC1 and VunLHY showed a rhythmic expression profile in leaves with a typical evening/night and morning/midday phased expression. The diel patterns were not completely robust and only VungGI and VungELF3 retained a rhythmic pattern under free running conditions of darkness. Under field conditions, rhythmicity and phasing apparently faded during early pod and seed development and was regained in ripening pods for VunTOC1 and VunLHY. Mature seeds showed a rhythmic expression of VunGI resembling leaf tissue under controlled growth chamber conditions. Comparing time windows during developmental stages we found that VunCVC and VunLEG were significantly down regulated during the night in mature pods as compared to intermediate ripe pods, while changes in seeds were non-significant due to high variance. The rhythmic expression under field conditions was lost under growth chamber conditions.

CONCLUSIONS: The core clock gene network is conserved in cowpea leaves showing a robust diel expression pattern except VunELF3 under growth chamber conditions. There appears to be a clock transcriptional reprogramming in pods and seeds compared to leaves. Storage protein deposition may be circadian regulated under field conditions but the strong environmental signals are not met under artificial growth conditions. Diel expression pattern in field conditions may result in better usage of energy for protein storage.}, } @article {pmid29444634, year = {2018}, author = {Latendresse, M and Karp, PD}, title = {Evaluation of reaction gap-filling accuracy by randomization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {53}, pmid = {29444634}, issn = {1471-2105}, support = {R01 GM075742/GM/NIGMS NIH HHS/United States ; GM075742/NH/NIH HHS/United States ; }, mesh = {Algorithms ; Genomics ; Metabolic Flux Analysis/*methods ; *Models, Biological ; Programming, Linear ; Software ; }, abstract = {BACKGROUND: Completion of genome-scale flux-balance models using computational reaction gap-filling is a widely used approach, but its accuracy is not well known.

RESULTS: We report on computational experiments of reaction gap filling in which we generated degraded versions of the EcoCyc-20.0-GEM model by randomly removing flux-carrying reactions from a growing model. We gap-filled the degraded models and compared the resulting gap-filled models with the original model. Gap-filling was performed by the Pathway Tools MetaFlux software using its General Development Mode (GenDev) and its Fast Development Mode (FastDev). We explored 12 GenDev variants including two linear solvers (SCIP and CPLEX) for solving the Mixed Integer Linear Programming (MILP) problems for gap filling; three different sets of linear constraints were applied; and two MILP methods were implemented. We compared these 13 variants according to accuracy, speed, and amount of information returned to the user.

CONCLUSIONS: We observed large variation among the performance of the 13 gap-filling variants. Although no variant was best in all dimensions, we found one variant that was fast, accurate, and returned more information to the user. Some gap-filling variants were inaccurate, producing solutions that were non-minimum or invalid (did not enable model growth). The best GenDev variant showed a best average precision of 87% and a best average recall of 61%. FastDev showed an average precision of 71% and an average recall of 59%. Thus, using the most accurate variant, approximately 13% of the gap-filled reactions were incorrect (were not the reactions removed from the model), and 39% of gap-filled reactions were not found, suggesting that curation is still an important aspect of metabolic-model development.}, } @article {pmid29444492, year = {2018}, author = {Veening, JW and Tamayo, R}, title = {Editorial overview: Bacterial cell regulation: from genes to complex environments.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {110-114}, doi = {10.1016/j.mib.2018.01.005}, pmid = {29444492}, issn = {1879-0364}, mesh = {Bacteria/genetics ; *Gene Expression Regulation, Bacterial ; Genes, Bacterial ; }, } @article {pmid29444377, year = {2018}, author = {Blanke, A and Pinheiro, M and Watson, PJ and Fagan, MJ}, title = {A biomechanical analysis of prognathous and orthognathous insect head capsules: evidence for a many-to-one mapping of form to function.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {665-674}, doi = {10.1111/jeb.13251}, pmid = {29444377}, issn = {1420-9101}, abstract = {Insect head shapes are remarkably variable, but the influences of these changes on biomechanical performance are unclear. Among 'basal' winged insects, such as dragonflies, mayflies, earwigs and stoneflies, some of the most prominent anatomical changes are the general mouthpart orientation, eye size and the connection of the endoskeleton to the head. Here, we assess these variations as well as differing ridge and sclerite configurations using modern engineering methods including multibody dynamics modelling and finite element analysis in order to quantify and compare the influence of anatomical changes on strain in particular head regions and the whole head. We show that a range of peculiar structures such as the genal/subgenal, epistomal and circumocular areas are consistently highly loaded in all species, despite drastically differing morphologies in species with forward-projecting (prognathous) and downward-projecting (orthognathous) mouthparts. Sensitivity analyses show that the presence of eyes has a negligible influence on head capsule strain if a circumocular ridge is present. In contrast, the connection of the dorsal endoskeletal arms to the head capsule especially affects overall head loading in species with downward-projecting mouthparts. Analysis of the relative strains between species for each head region reveals that concerted changes in head substructures such as the subgenal area, the endoskeleton and the epistomal area lead to a consistent relative loading for the whole head capsule and vulnerable structures such as the eyes. It appears that biting-chewing loads are managed by a system of strengthening ridges on the head capsule irrespective of the general mouthpart and head orientation. Concerted changes in ridge and endoskeleton configuration might allow for more radical anatomical changes such as the general mouthpart orientation, which could be an explanation for the variability of this trait among insects. In an evolutionary context, many-to-one mapping of strain patterns onto a relatively similar overall head loading indeed could have fostered the dynamic diversification processes seen in insects.}, } @article {pmid29444265, year = {2018}, author = {Williamson, CJ and Anesio, AM and Cook, J and Tedstone, A and Poniecka, E and Holland, A and Fagan, D and Tranter, M and Yallop, ML}, title = {Ice algal bloom development on the surface of the Greenland Ice Sheet.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, pmid = {29444265}, issn = {1574-6941}, abstract = {It is fundamental to understand the development of Zygnematophycean (Streptophyte) micro-algal blooms within Greenland Ice Sheet (GrIS) supraglacial environments, given their potential to significantly impact both physical (melt) and chemical (carbon and nutrient cycling) surface characteristics. Here, we report on a space-for-time assessment of a GrIS ice algal bloom, achieved by sampling an ∼85 km transect spanning the south-western GrIS bare ice zone during the 2016 ablation season. Cell abundances ranged from 0 to 1.6 × 104 cells ml-1, with algal biomass demonstrated to increase in surface ice with time since snow line retreat (R2 = 0.73, P < 0.05). A suite of light harvesting and photo-protective pigments were quantified across transects (chlorophylls, carotenoids and phenols) and shown to increase in concert with algal biomass. Ice algal communities drove net autotrophy of surface ice, with maximal rates of net production averaging 0.52 ± 0.04 mg C l-1 d-1, and a total accumulation of 1.306 Gg C (15.82 ± 8.14 kg C km-2) predicted for the 2016 ablation season across an 8.24 × 104 km2 region of the GrIS. By advancing our understanding of ice algal bloom development, this study marks an important step toward projecting bloom occurrence and impacts into the future.}, } @article {pmid29444218, year = {2018}, author = {Chua, MJ and Campen, RL and Wahl, L and Grzymski, JJ and Mikucki, JA}, title = {Genomic and physiological characterization and description of Marinobacter gelidimuriae sp. nov., a psychrophilic, moderate halophile from Blood Falls, an antarctic subglacial brine.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy021}, pmid = {29444218}, issn = {1574-6941}, abstract = {Antarctic subice environments are diverse, underexplored microbial habitats. Here, we describe the ecophysiology and annotated genome of a Marinobacter strain isolated from a cold, saline, iron-rich subglacial outflow of the Taylor Glacier, Antarctica. This strain (BF04_CF4) grows fastest at neutral pH (range 6-10), is psychrophilic (range: 0°C-20°C), moderately halophilic (range: 0.8%-15% NaCl) and hosts genes encoding potential low temperature and high salt adaptations. The predicted proteome suggests it utilizes fewer charged amino acids than a mesophilic Marinobacter strain. BF04_CF4 has increased concentrations of membrane unsaturated fatty acids including palmitoleic (33%) and oleic (27.5%) acids that may help maintain cell membrane fluidity at low temperatures. The genome encodes proteins for compatible solute biosynthesis and transport, which are known to be important for growth in saline environments. Physiological verification of predicted metabolic functions demonstrate BF04_CF4 is capable of denitrification and may facilitate iron oxidation. Our data indicate that strain BF04_CF4 represents a new Marinobacter species, Marinobacter gelidimuriae sp. nov., that appears well suited for the subglacial environment it was isolated from. Marinobacter species have been isolated from other cold, saline environments in the McMurdo Dry Valleys and permanently cold environments globally suggesting that this lineage is cosmopolitan and ecologically relevant in icy brines.}, } @article {pmid29443969, year = {2018}, author = {Saito, F and Hirayasu, K and Satoh, T and Wang, CW and Lusingu, J and Arimori, T and Shida, K and Palacpac, NMQ and Itagaki, S and Iwanaga, S and Takashima, E and Tsuboi, T and Kohyama, M and Suenaga, T and Colonna, M and Takagi, J and Lavstsen, T and Horii, T and Arase, H}, title = {Corrigendum: Immune evasion of Plasmodium falciparum by RIFIN via inhibitory receptors.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {554}, pmid = {29443969}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24994.}, } @article {pmid29443968, year = {2018}, author = {Pritchard, HD}, title = {Retraction: Asia's glaciers are a regionally important buffer against drought.}, journal = {Nature}, volume = {555}, number = {7695}, pages = {274}, pmid = {29443968}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature22062.}, } @article {pmid29443967, year = {2018}, author = {Monteiro, JM and Pereira, AR and Reichmann, NT and Saraiva, BM and Fernandes, PB and Veiga, H and Tavares, AC and Santos, M and Ferreira, MT and Macário, V and VanNieuwenhze, MS and Filipe, SR and Pinho, MG}, title = {Peptidoglycan synthesis drives an FtsZ-treadmilling-independent step of cytokinesis.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {528-532}, pmid = {29443967}, issn = {1476-4687}, support = {310987//European Research Council/International ; R01 GM113172/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/metabolism ; Cell Wall/chemistry/metabolism ; *Cytokinesis ; Cytoskeletal Proteins/metabolism ; Kinetics ; Microscopy, Fluorescence ; Peptidoglycan/*biosynthesis ; Phospholipid Transfer Proteins/*metabolism ; Pyridines/pharmacology ; Single-Cell Analysis ; Staphylococcus aureus/*cytology/drug effects/*metabolism ; Thiazoles/pharmacology ; Uridine Diphosphate N-Acetylmuramic Acid/analogs & derivatives/metabolism ; }, abstract = {Peptidoglycan is the main component of the bacterial wall and protects cells from the mechanical stress that results from high intracellular turgor. Peptidoglycan biosynthesis is very similar in all bacteria; bacterial shapes are therefore mainly determined by the spatial and temporal regulation of peptidoglycan synthesis rather than by the chemical composition of peptidoglycan. The form of rod-shaped bacteria, such as Bacillus subtilis or Escherichia coli, is generated by the action of two peptidoglycan synthesis machineries that act at the septum and at the lateral wall in processes coordinated by the cytoskeletal proteins FtsZ and MreB, respectively. The tubulin homologue FtsZ is the first protein recruited to the division site, where it assembles in filaments-forming the Z ring-that undergo treadmilling and recruit later divisome proteins. The rate of treadmilling in B. subtilis controls the rates of both peptidoglycan synthesis and cell division. The actin homologue MreB forms discrete patches that move circumferentially around the cell in tracks perpendicular to the long axis of the cell, and organize the insertion of new cell wall during elongation. Cocci such as Staphylococcus aureus possess only one type of peptidoglycan synthesis machinery, which is diverted from the cell periphery to the septum in preparation for division. The molecular cue that coordinates this transition has remained elusive. Here we investigate the localization of S. aureus peptidoglycan biosynthesis proteins and show that the recruitment of the putative lipid II flippase MurJ to the septum, by the DivIB-DivIC-FtsL complex, drives peptidoglycan incorporation to the midcell. MurJ recruitment corresponds to a turning point in cytokinesis, which is slow and dependent on FtsZ treadmilling before MurJ arrival but becomes faster and independent of FtsZ treadmilling after peptidoglycan synthesis activity is directed to the septum, where it provides additional force for cell envelope constriction.}, } @article {pmid29443966, year = {2018}, author = {Taubert, F and Fischer, R and Groeneveld, J and Lehmann, S and Müller, MS and Rödig, E and Wiegand, T and Huth, A}, title = {Global patterns of tropical forest fragmentation.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {519-522}, pmid = {29443966}, issn = {1476-4687}, mesh = {Biomass ; Conservation of Natural Resources/*statistics & numerical data ; Forestry/*statistics & numerical data ; *Forests ; *Geographic Mapping ; Satellite Imagery ; Trees/*growth & development ; *Tropical Climate ; }, abstract = {Remote sensing enables the quantification of tropical deforestation with high spatial resolution. This in-depth mapping has led to substantial advances in the analysis of continent-wide fragmentation of tropical forests. Here we identified approximately 130 million forest fragments in three continents that show surprisingly similar power-law size and perimeter distributions as well as fractal dimensions. Power-law distributions have been observed in many natural phenomena such as wildfires, landslides and earthquakes. The principles of percolation theory provide one explanation for the observed patterns, and suggest that forest fragmentation is close to the critical point of percolation; simulation modelling also supports this hypothesis. The observed patterns emerge not only from random deforestation, which can be described by percolation theory, but also from a wide range of deforestation and forest-recovery regimes. Our models predict that additional forest loss will result in a large increase in the total number of forest fragments-at maximum by a factor of 33 over 50 years-as well as a decrease in their size, and that these consequences could be partly mitigated by reforestation and forest protection.}, } @article {pmid29443965, year = {2018}, author = {Vanlandewijck, M and He, L and Mäe, MA and Andrae, J and Ando, K and Del Gaudio, F and Nahar, K and Lebouvier, T and Laviña, B and Gouveia, L and Sun, Y and Raschperger, E and Räsänen, M and Zarb, Y and Mochizuki, N and Keller, A and Lendahl, U and Betsholtz, C}, title = {A molecular atlas of cell types and zonation in the brain vasculature.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {475-480}, pmid = {29443965}, issn = {1476-4687}, support = {159514//Swiss National Science Foundation/Switzerland ; }, mesh = {Animals ; Arteries/cytology ; Arterioles/cytology ; Blood Vessels/*cytology ; Brain/*blood supply/*cytology ; Capillaries/cytology ; Endothelial Cells/*classification ; Female ; Fibroblasts/classification ; Male ; Mice ; Myocytes, Smooth Muscle/classification ; Organ Specificity ; Pericytes/classification ; Single-Cell Analysis ; Transcriptome ; Veins/cytology ; }, abstract = {Cerebrovascular disease is the third most common cause of death in developed countries, but our understanding of the cells that compose the cerebral vasculature is limited. Here, using vascular single-cell transcriptomics, we provide molecular definitions for the principal types of blood vascular and vessel-associated cells in the adult mouse brain. We uncover the transcriptional basis of the gradual phenotypic change (zonation) along the arteriovenous axis and reveal unexpected cell type differences: a seamless continuum for endothelial cells versus a punctuated continuum for mural cells. We also provide insight into pericyte organotypicity and define a population of perivascular fibroblast-like cells that are present on all vessel types except capillaries. Our work illustrates the power of single-cell transcriptomics to decode the higher organizational principles of a tissue and may provide the initial chapter in a molecular encyclopaedia of the mammalian vasculature.}, } @article {pmid29443964, year = {2018}, author = {Tauriello, DVF and Palomo-Ponce, S and Stork, D and Berenguer-Llergo, A and Badia-Ramentol, J and Iglesias, M and Sevillano, M and Ibiza, S and Cañellas, A and Hernando-Momblona, X and Byrom, D and Matarin, JA and Calon, A and Rivas, EI and Nebreda, AR and Riera, A and Attolini, CS and Batlle, E}, title = {TGFβ drives immune evasion in genetically reconstituted colon cancer metastasis.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {538-543}, pmid = {29443964}, issn = {1476-4687}, mesh = {Alleles ; Animals ; Cell Differentiation/drug effects ; Colonic Neoplasms/drug therapy/*genetics/immunology/*pathology ; Disease Models, Animal ; Drug Synergism ; Female ; Humans ; *Immune Evasion/drug effects ; *Immunotherapy ; Intestinal Mucosa/metabolism ; Intestines/drug effects/pathology ; Liver Neoplasms/drug therapy/immunology/secondary ; Male ; Mice ; Mutation ; Neoplasm Metastasis/drug therapy/*genetics/*immunology/pathology ; Programmed Cell Death 1 Receptor/antagonists & inhibitors ; Stem Cells/drug effects/metabolism/pathology ; T-Lymphocytes, Cytotoxic/cytology/drug effects/immunology ; Th1 Cells/drug effects/immunology ; Transforming Growth Factor beta/antagonists & inhibitors/*immunology ; Tumor Microenvironment/drug effects/immunology ; }, abstract = {Most patients with colorectal cancer die as a result of the disease spreading to other organs. However, no prevalent mutations have been associated with metastatic colorectal cancers. Instead, particular features of the tumour microenvironment, such as lack of T-cell infiltration, low type 1 T-helper cell (TH1) activity and reduced immune cytotoxicity or increased TGFβ levels predict adverse outcomes in patients with colorectal cancer. Here we analyse the interplay between genetic alterations and the tumour microenvironment by crossing mice bearing conditional alleles of four main colorectal cancer mutations in intestinal stem cells. Quadruple-mutant mice developed metastatic intestinal tumours that display key hallmarks of human microsatellite-stable colorectal cancers, including low mutational burden, T-cell exclusion and TGFβ-activated stroma. Inhibition of the PD-1-PD-L1 immune checkpoint provoked a limited response in this model system. By contrast, inhibition of TGFβ unleashed a potent and enduring cytotoxic T-cell response against tumour cells that prevented metastasis. In mice with progressive liver metastatic disease, blockade of TGFβ signalling rendered tumours susceptible to anti-PD-1-PD-L1 therapy. Our data show that increased TGFβ in the tumour microenvironment represents a primary mechanism of immune evasion that promotes T-cell exclusion and blocks acquisition of the TH1-effector phenotype. Immunotherapies directed against TGFβ signalling may therefore have broad applications in treating patients with advanced colorectal cancer.}, } @article {pmid29443963, year = {2018}, author = {, }, title = {Erratum: Measurement of the multi-TeV neutrino interaction cross-section with IceCube using Earth absorption.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {554}, pmid = {29443963}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24459.}, } @article {pmid29443962, year = {2018}, author = {Watson, TF and Philips, SGJ and Kawakami, E and Ward, DR and Scarlino, P and Veldhorst, M and Savage, DE and Lagally, MG and Friesen, M and Coppersmith, SN and Eriksson, MA and Vandersypen, LMK}, title = {A programmable two-qubit quantum processor in silicon.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {633-637}, pmid = {29443962}, issn = {1476-4687}, abstract = {Now that it is possible to achieve measurement and control fidelities for individual quantum bits (qubits) above the threshold for fault tolerance, attention is moving towards the difficult task of scaling up the number of physical qubits to the large numbers that are needed for fault-tolerant quantum computing. In this context, quantum-dot-based spin qubits could have substantial advantages over other types of qubit owing to their potential for all-electrical operation and ability to be integrated at high density onto an industrial platform. Initialization, readout and single- and two-qubit gates have been demonstrated in various quantum-dot-based qubit representations. However, as seen with small-scale demonstrations of quantum computers using other types of qubit, combining these elements leads to challenges related to qubit crosstalk, state leakage, calibration and control hardware. Here we overcome these challenges by using carefully designed control techniques to demonstrate a programmable two-qubit quantum processor in a silicon device that can perform the Deutsch-Josza algorithm and the Grover search algorithm-canonical examples of quantum algorithms that outperform their classical analogues. We characterize the entanglement in our processor by using quantum-state tomography of Bell states, measuring state fidelities of 85-89 per cent and concurrences of 73-82 per cent. These results pave the way for larger-scale quantum computers that use spins confined to quantum dots.}, } @article {pmid29443961, year = {2018}, author = {Mi, X and Benito, M and Putz, S and Zajac, DM and Taylor, JM and Burkard, G and Petta, JR}, title = {A coherent spin-photon interface in silicon.}, journal = {Nature}, volume = {555}, number = {7698}, pages = {599-603}, pmid = {29443961}, issn = {1476-4687}, abstract = {Electron spins in silicon quantum dots are attractive systems for quantum computing owing to their long coherence times and the promise of rapid scaling of the number of dots in a system using semiconductor fabrication techniques. Although nearest-neighbour exchange coupling of two spins has been demonstrated, the interaction of spins via microwave-frequency photons could enable long-distance spin-spin coupling and connections between arbitrary pairs of qubits ('all-to-all' connectivity) in a spin-based quantum processor. Realizing coherent spin-photon coupling is challenging because of the small magnetic-dipole moment of a single spin, which limits magnetic-dipole coupling rates to less than 1 kilohertz. Here we demonstrate strong coupling between a single spin in silicon and a single microwave-frequency photon, with spin-photon coupling rates of more than 10 megahertz. The mechanism that enables the coherent spin-photon interactions is based on spin-charge hybridization in the presence of a magnetic-field gradient. In addition to spin-photon coupling, we demonstrate coherent control and dispersive readout of a single spin. These results open up a direct path to entangling single spins using microwave-frequency photons.}, } @article {pmid29443960, year = {2018}, author = {Mariathasan, S and Turley, SJ and Nickles, D and Castiglioni, A and Yuen, K and Wang, Y and Kadel, EE and Koeppen, H and Astarita, JL and Cubas, R and Jhunjhunwala, S and Banchereau, R and Yang, Y and Guan, Y and Chalouni, C and Ziai, J and Şenbabaoğlu, Y and Santoro, S and Sheinson, D and Hung, J and Giltnane, JM and Pierce, AA and Mesh, K and Lianoglou, S and Riegler, J and Carano, RAD and Eriksson, P and Höglund, M and Somarriba, L and Halligan, DL and van der Heijden, MS and Loriot, Y and Rosenberg, JE and Fong, L and Mellman, I and Chen, DS and Green, M and Derleth, C and Fine, GD and Hegde, PS and Bourgon, R and Powles, T}, title = {TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {544-548}, pmid = {29443960}, issn = {1476-4687}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; 1R01CA194511/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies/immunology/pharmacology/therapeutic use ; Antibodies, Monoclonal/*pharmacology/*therapeutic use ; Antigens, Neoplasm/analysis/immunology/metabolism ; B7-H1 Antigen/*antagonists & inhibitors/immunology ; CD8-Positive T-Lymphocytes/cytology/*drug effects/immunology ; Cell Cycle Checkpoints/drug effects ; Cohort Studies ; Collagen/metabolism ; Disease Models, Animal ; Drug Resistance, Neoplasm/drug effects ; Fibroblasts/metabolism ; Humans ; Immunotherapy ; Mice ; Mutation ; Neoplasm Metastasis ; Phenotype ; Signal Transduction/drug effects ; Transforming Growth Factor beta/antagonists & inhibitors/*metabolism ; Treatment Outcome ; Tumor Microenvironment/immunology ; Urologic Neoplasms/*drug therapy/genetics/*immunology/pathology ; Urothelium/drug effects/immunology/*pathology ; }, abstract = {Therapeutic antibodies that block the programmed death-1 (PD-1)-programmed death-ligand 1 (PD-L1) pathway can induce robust and durable responses in patients with various cancers, including metastatic urothelial cancer. However, these responses only occur in a subset of patients. Elucidating the determinants of response and resistance is key to improving outcomes and developing new treatment strategies. Here we examined tumours from a large cohort of patients with metastatic urothelial cancer who were treated with an anti-PD-L1 agent (atezolizumab) and identified major determinants of clinical outcome. Response to treatment was associated with CD8+ T-effector cell phenotype and, to an even greater extent, high neoantigen or tumour mutation burden. Lack of response was associated with a signature of transforming growth factor β (TGFβ) signalling in fibroblasts. This occurred particularly in patients with tumours, which showed exclusion of CD8+ T cells from the tumour parenchyma that were instead found in the fibroblast- and collagen-rich peritumoural stroma; a common phenotype among patients with metastatic urothelial cancer. Using a mouse model that recapitulates this immune-excluded phenotype, we found that therapeutic co-administration of TGFβ-blocking and anti-PD-L1 antibodies reduced TGFβ signalling in stromal cells, facilitated T-cell penetration into the centre of tumours, and provoked vigorous anti-tumour immunity and tumour regression. Integration of these three independent biological features provides the best basis for understanding patient outcome in this setting and suggests that TGFβ shapes the tumour microenvironment to restrain anti-tumour immunity by restricting T-cell infiltration.}, } @article {pmid29443959, year = {2018}, author = {Cobo, I and Martinelli, P and Flández, M and Bakiri, L and Zhang, M and Carrillo-de-Santa-Pau, E and Jia, J and Sánchez-Arévalo Lobo, VJ and Megías, D and Felipe, I and Del Pozo, N and Millán, I and Thommesen, L and Bruland, T and Olson, SH and Smith, J and Schoonjans, K and Bamlet, WR and Petersen, GM and Malats, N and Amundadottir, LT and Wagner, EF and Real, FX}, title = {Transcriptional regulation by NR5A2 links differentiation and inflammation in the pancreas.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {533-537}, pmid = {29443959}, issn = {1476-4687}, support = {P50 CA102701/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Acinar Cells/metabolism/pathology ; Animals ; Cell Differentiation/*genetics ; Chromatin/genetics/metabolism ; Epithelial Cells/metabolism/pathology ; *Gene Expression Regulation ; Gene Regulatory Networks/genetics ; Genes, jun/genetics ; Heterozygote ; Humans ; Inflammation/*genetics ; Mice ; Organ Specificity/genetics ; Pancreas/*metabolism/*pathology ; Pancreatitis/genetics ; Promoter Regions, Genetic/genetics ; Receptors, Cytoplasmic and Nuclear/deficiency/genetics/*metabolism ; Transcription Factor AP-1/metabolism ; *Transcriptome ; }, abstract = {Chronic inflammation increases the risk of developing one of several types of cancer. Inflammatory responses are currently thought to be controlled by mechanisms that rely on transcriptional networks that are distinct from those involved in cell differentiation. The orphan nuclear receptor NR5A2 participates in a wide variety of processes, including cholesterol and glucose metabolism in the liver, resolution of endoplasmic reticulum stress, intestinal glucocorticoid production, pancreatic development and acinar differentiation. In genome-wide association studies, single nucleotide polymorphisms in the vicinity of NR5A2 have previously been associated with the risk of pancreatic adenocarcinoma. In mice, Nr5a2 heterozygosity sensitizes the pancreas to damage, impairs regeneration and cooperates with mutant Kras in tumour progression. Here, using a global transcriptomic analysis, we describe an epithelial-cell-autonomous basal pre-inflammatory state in the pancreas of Nr5a2+/- mice that is reminiscent of the early stages of pancreatitis-induced inflammation and is conserved in histologically normal human pancreases with reduced expression of NR5A2 mRNA. In Nr5a2+/-mice, NR5A2 undergoes a marked transcriptional switch, relocating from differentiation-specific to inflammatory genes and thereby promoting gene transcription that is dependent on the AP-1 transcription factor. Pancreatic deletion of Jun rescues the pre-inflammatory phenotype, as well as binding of NR5A2 to inflammatory gene promoters and the defective regenerative response to damage. These findings support the notion that, in the pancreas, the transcriptional networks involved in differentiation-specific functions also suppress inflammatory programmes. Under conditions of genetic or environmental constraint, these networks can be subverted to foster inflammation.}, } @article {pmid29443958, year = {2018}, author = {Barriga, EH and Franze, K and Charras, G and Mayor, R}, title = {Tissue stiffening coordinates morphogenesis by triggering collective cell migration in vivo.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {523-527}, pmid = {29443958}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; G1100312//Medical Research Council/United Kingdom ; R21 HD080585/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; *Cell Movement ; Epithelial-Mesenchymal Transition ; Extracellular Matrix ; Female ; Gastrulation ; Hardness ; Integrins/metabolism ; *Mechanotransduction, Cellular ; Mesoderm/cytology/embryology/*physiology ; *Morphogenesis ; Neural Crest/*cytology ; Xenopus laevis/*embryology ; }, abstract = {Collective cell migration is essential for morphogenesis, tissue remodelling and cancer invasion. In vivo, groups of cells move in an orchestrated way through tissues. This movement involves mechanical as well as molecular interactions between cells and their environment. While the role of molecular signals in collective cell migration is comparatively well understood, how tissue mechanics influence collective cell migration in vivo remains unknown. Here we investigated the importance of mechanical cues in the collective migration of the Xenopus laevis neural crest cells, an embryonic cell population whose migratory behaviour has been likened to cancer invasion. We found that, during morphogenesis, the head mesoderm underlying the cephalic neural crest stiffens. This stiffening initiates an epithelial-to-mesenchymal transition in neural crest cells and triggers their collective migration. To detect changes in their mechanical environment, neural crest cells use mechanosensation mediated by the integrin-vinculin-talin complex. By performing mechanical and molecular manipulations, we show that mesoderm stiffening is necessary and sufficient to trigger neural crest migration. Finally, we demonstrate that convergent extension of the mesoderm, which starts during gastrulation, leads to increased mesoderm stiffness by increasing the cell density underneath the neural crest. These results show that convergent extension of the mesoderm has a role as a mechanical coordinator of morphogenesis, and reveal a link between two apparently unconnected processes-gastrulation and neural crest migration-via changes in tissue mechanics. Overall, we demonstrate that changes in substrate stiffness can trigger collective cell migration by promoting epithelial-to-mesenchymal transition in vivo. More broadly, our results raise the idea that tissue mechanics combines with molecular effectors to coordinate morphogenesis.}, } @article {pmid29442448, year = {2018}, author = {Wackett, LP}, title = {Horizontal gene transfer (HGT) in biodegradation: An annotated selection of world wide web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {920-921}, doi = {10.1111/1462-2920.14052}, pmid = {29442448}, issn = {1462-2920}, } @article {pmid29442447, year = {2018}, author = {}, title = {Corrigendum.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {922}, doi = {10.1111/1462-2920.14040}, pmid = {29442447}, issn = {1462-2920}, } @article {pmid29442366, year = {2018}, author = {Abu Awad, D and Roze, D}, title = {Effects of partial selfing on the equilibrium genetic variance, mutation load, and inbreeding depression under stabilizing selection.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {751-769}, doi = {10.1111/evo.13449}, pmid = {29442366}, issn = {1558-5646}, abstract = {The mating system of a species is expected to have important effects on its genetic diversity. In this article, we explore the effects of partial selfing on the equilibrium genetic variance Vg , mutation load L, and inbreeding depression δ under stabilizing selection acting on a arbitrary number n of quantitative traits coded by biallelic loci with additive effects. When the U/n ratio is low (where U is the total haploid mutation rate on selected traits) and effective recombination rates are sufficiently high, genetic associations between loci are negligible and the genetic variance, mutation load, and inbreeding depression are well predicted by approximations based on single-locus models. For higher values of U/n and/or lower effective recombination, moderate genetic associations generated by epistasis tend to increase Vg , L, and δ, this regime being well predicted by approximations including the effects of pairwise associations between loci. For yet higher values of U/n and/or lower effective recombination, a different regime is reached under which the maintenance of coadapted gene complexes reduces Vg , L, and δ. Simulations indicate that the values of Vg , L, and δ are little affected by assumptions regarding the number of possible alleles per locus.}, } @article {pmid29442149, year = {2018}, author = {Fraunhofer, ME and Jakob, F and Vogel, RF}, title = {Influence of Different Sugars and Initial pH on β-Glucan Formation by Lactobacillus brevis TMW 1.2112.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {794-802}, pmid = {29442149}, issn = {1432-0991}, support = {18194 N//Allianz Industrie Forschung/ ; }, mesh = {Beer/analysis/microbiology ; *Carbohydrate Metabolism ; Carbohydrates/chemistry ; Culture Media/chemistry/metabolism ; Fermentation ; Hydrogen-Ion Concentration ; Lactobacillus brevis/*metabolism ; beta-Glucans/*metabolism ; }, abstract = {We wanted to identify key factors influencing the extent of β-glucan production by Lactobacillus brevis TMW 1.2112, which has been isolated from viscous, spoiled beer and which could contribute to viscosity increases of spoiled beverages via exopolysaccharide (EPS) production. In this way, we analyzed the influence of different initial pH values and carbohydrate sources on growth of and slime/β-glucan formation by this strain. In a screening of 48 carbohydrates, 14 fermentable sugars which enabled growth were identified. These sugars were further investigated regarding their EPS formation-promoting properties. The hexose-based mono- and di-saccharides enabled slime formation, while all pentoses failed to cause any thickening effect. The strongest slime formation was observed upon growth on D-maltose, the weakest on D-fructose. A lower initial pH (4.3) caused significant higher viscosities than an initially higher one (pH 6.2). This effect was independent from the carbohydrate supplied. Although the thickening of nutrient media by L. brevis TMW 1.2112 strongly depended on the initial pH and the available carbon source, all isolated polysaccharides were exclusively composed of glucose moieties and exhibited highly similar elution profiles after separation via asymmetric flow field-flow fractionation independently of the provided carbon source. Our results suggest that the extent of β-glucan/slime formation by special L. brevis strains isolated from the brewery environment is strongly influenced by the initial pH and the availability of certain EPS formation-promoting sugars with maltose being the most favored carbohydrate for the regulated and directive biosynthesis of capsular β-glucan.}, } @article {pmid29441732, year = {2018}, author = {Wackett, LP}, title = {Milestones in environmental microbiology: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {108-109}, doi = {10.1111/1758-2229.12622}, pmid = {29441732}, issn = {1758-2229}, } @article {pmid29441731, year = {2018}, author = {Timmis, K and Timmis, J}, title = {Environmental Microbiology Reports is 10!.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {5-6}, doi = {10.1111/1758-2229.12611}, pmid = {29441731}, issn = {1758-2229}, } @article {pmid29441720, year = {2018}, author = {Kim, DH and Lee, BY and Kim, HS and Jeong, CB and Hwang, DS and Kim, IC and Lee, JS}, title = {Identification and characterization of homeobox (Hox) genes and conservation of the single Hox cluster (324.6 kb) in the water flea Daphnia magna.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {2}, pages = {76-82}, doi = {10.1002/jez.b.22793}, pmid = {29441720}, issn = {1552-5015}, mesh = {Animals ; *Conserved Sequence ; DNA Transposable Elements ; Daphnia/*genetics ; Gene Expression Regulation, Developmental ; Genes, Homeobox/*genetics ; Genome ; *Multigene Family ; Species Specificity ; }, abstract = {We report the complete sequence analysis of the entire complement of eight typical homeobox (Hox) genes (Lab, Pb, Dfd, Scr, Antp, Ubx, Abd-A, and Abd-B) and two other genes (Hox3 and Ftz) in a 324.6-kb region in the water flea Daphnia magna. In the cluster of D. magna Hox genes, we found one long interspersed nuclear element (LINE)/R2-NeSL between Ubx and Abd-A that was not present in Daphnia pulex Hox genes. In basal expression of Hox genes at different developmental stages, biothorax complex genes (Ubx, Abd-A, and Abd-B) and some antennapedia complex genes (Lab, Scr, Antp) were moderately expressed, but the Hox3 gene was barely expressed. Three homeobox genes (Antp, Ubx, Abd-A) were highly expressed at 6-7 days after release from the brood chamber and/or in the adult stage. The structural array and transcribed orientation of Dm-Hox genes were identical to those of the sister species D. pulex (∼340 kb), indicating that the Hox gene structure in daphnids is highly conserved. However, Dm- and Dp-Hox3, -deformed (Dfd), and -fushi tarazu (Ftz) genes varied from orthologous genes in pancrustacean species.}, } @article {pmid29441716, year = {2018}, author = {Koch, RE and Hill, GE}, title = {Behavioural mating displays depend on mitochondrial function: a potential mechanism for linking behaviour to individual condition.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1387-1398}, doi = {10.1111/brv.12400}, pmid = {29441716}, issn = {1469-185X}, abstract = {Males of many animal species court females using complex behavioural displays that are challenging to produce, and some of these displays have been shown to be associated with aspects of male quality. However, the mechanisms by which behavioural displays are linked to individual condition remain uncertain. Herein, we illustrate fundamental mechanistic connections between mitochondrial function and neurogenesis, energy production, and a variety of pathways that underlie the ability of an individual to perform complex behaviours. We consider the biomedical evidence for how mitochondrial activity shapes neurogenesis during development and neural function in adulthood, and how both genetics and environmental conditions can cause variation in mitochondrial function in wild animals. An individual's mitochondrial phenotype determines not just metabolism and available energy, but also appears to serve as an important driver of capacity to perform cognitively complex and other challenging display behaviours. We apply this concept to the example of birdsong, a well-studied display behaviour with known links to neural pathways, and we describe how mitochondrial involvement in a variety of important internal processes creates links between display quality and key traits like immunocompetence. By synthesizing the intimate involvement of mitochondria in neural processes with the physiological bases of display behaviour, we aim to provide new mechanistic explanations for information that females may gain by assessing complex male displays.}, } @article {pmid29441701, year = {2018}, author = {Maciá-Vicente, JG and Shi, YN and Cheikh-Ali, Z and Grün, P and Glynou, K and Kia, SH and Piepenbring, M and Bode, HB}, title = {Metabolomics-based chemotaxonomy of root endophytic fungi for natural products discovery.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1253-1270}, doi = {10.1111/1462-2920.14072}, pmid = {29441701}, issn = {1462-2920}, abstract = {Fungi are prolific producers of natural products routinely screened for biotechnological applications, and those living endophytically within plants attract particular attention because of their purported chemical diversity. However, the harnessing of their biosynthetic potential is hampered by a large and often cryptic phylogenetic and ecological diversity, coupled with a lack of large-scale natural products' dereplication studies. To guide efforts to discover new chemistries among root-endophytic fungi, we analyzed the natural products produced by 822 strains using an untargeted UPLC-ESI-MS/MS-based approach and linked the patterns of chemical features to fungal lineages. We detected 17 809 compounds of which 7951 were classified in 1992 molecular families, whereas the remaining were considered unique chemistries. Our approach allowed to annotate 1191 compounds with different degrees of accuracy, many of which had known fungal origins. Approximately 61% of the compounds were specific of a fungal order, and differences were observed across lineages in the diversity and characteristics of their chemistries. Chemical profiles also showed variable chemosystematic values across lineages, ranging from relative homogeneity to high heterogeneity among related fungi. Our results provide an extensive resource to dereplicate fungal natural products and may assist future discovery programs by providing a guide for the selection of target fungi.}, } @article {pmid29441670, year = {2018}, author = {Espinosa, J and Labella, JI and Cantos, R and Contreras, A}, title = {Energy drives the dynamic localization of cyanobacterial nitrogen regulators during diurnal cycles.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1240-1252}, doi = {10.1111/1462-2920.14071}, pmid = {29441670}, issn = {1462-2920}, abstract = {Cyanobacteria, phototrophic organisms performing oxygenic photosynthesis, must adapt their metabolic processes to the challenges imposed by the succession of days and nights. Two conserved cyanobacterial proteins, PII and PipX, function as hubs of the nitrogen interaction network, forming complexes with a variety of diverse targets. While PII proteins are found in all three domains of life as integrators of signals of the nitrogen and carbon balance, PipX proteins are unique to cyanobacteria, where they provide a mechanistic link between PII signalling and the control of gene expression by the global nitrogen regulator NtcA. Here we demonstrate that PII and PipX display distinct localization patterns during diurnal cycles, co-localizing into the same foci at the periphery and poles of the cells during dark periods, a circadian-independent process requiring a low ATP/ADP ratio. Genetic, cellular biology and biochemical approaches used here provide new insights into the nitrogen regulatory network, calling attention to the roles of PII as energy sensors and its interactions with PipX in the context of essential signalling pathways. This study expands the contribution of the nitrogen regulators PII and PipX to integrate and transduce key environmental signals that allow cyanobacteria to thrive in our planet.}, } @article {pmid29441664, year = {2018}, author = {Souffreau, C and Busschaert, P and Denis, C and Van Wichelen, J and Lievens, B and Vyverman, W and De Meester, L}, title = {A comparative hierarchical analysis of bacterioplankton and biofilm metacommunity structure in an interconnected pond system.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1271-1282}, doi = {10.1111/1462-2920.14073}, pmid = {29441664}, issn = {1462-2920}, abstract = {It is unknown whether bacterioplankton and biofilm communities are structured by the same ecological processes, and whether they influence each other through continuous dispersal (known as mass effects). Using a hierarchical sampling approach we compared the relative importance of ecological processes structuring the dominant fraction (relative abundance ≥0.1%) of bacterioplankton and biofilm communities from three microhabitats (open water, Nuphar and Phragmites sites) at within- and among-pond scale in a set of 14 interconnected shallow ponds. Our results demonstrate that while bacterioplankton and biofilm communities are highly distinct, a similar hierarchy of ecological processes is acting on them. For both community types, most variation in community composition was determined by pond identity and environmental variables, with no effect of space. The highest β-diversity within each community type was observed among ponds, while microhabitat type (Nuphar, Phragmites, open water) significantly influenced biofilm communities but not bacterioplankton. Mass effects among bacterioplankton and biofilm communities were not detected, as suggested by the absence of within-site covariation of biofilm and bacterioplankton communities. Both biofilm and plankton communities were thus highly structured by environmental factors (i.e., species sorting), with among-lake variation being more important than within-lake variation, whereas dispersal limitation and mass effects were not observed.}, } @article {pmid29441658, year = {2018}, author = {Pent, M and Hiltunen, M and Põldmaa, K and Furneaux, B and Hildebrand, F and Johannesson, H and Ryberg, M and Bahram, M}, title = {Host genetic variation strongly influences the microbiome structure and function in fungal fruiting-bodies.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1641-1650}, doi = {10.1111/1462-2920.14069}, pmid = {29441658}, issn = {1462-2920}, abstract = {Despite increasing knowledge on host-associated microbiomes, little is known about mechanisms underlying fungus-microbiome interactions. This study aimed to examine the relative importance of host genetic, geographic and environmental variations in structuring fungus-associated microbiomes. We analyzed the taxonomic composition and function of microbiomes inhabiting fungal fruiting-bodies in relation to host genetic variation, soil pH and geographic distance between samples. For this, we sequenced the metagenomes of 40 fruiting-bodies collected from six fairy rings (i.e., genets) of a saprotrophic fungus Marasmius oreades. Our analyses revealed that fine genetic variations between host fungi could strongly affect their associated microbiome, explaining, respectively, 25% and 37% of the variation in microbiome structure and function, whereas geographic distance and soil pH remained of secondary importance. These results, together with the smaller genome size of fungi compared to other eukaryotes, suggest that fruiting-bodies are suitable for further genome-centric studies on host-microbiome interactions.}, } @article {pmid29441527, year = {2018}, author = {Pearse, WD and Morales-Castilla, I and James, LS and Farrell, M and Boivin, F and Davies, TJ}, title = {Global macroevolution and macroecology of passerine song.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {944-960}, doi = {10.1111/evo.13450}, pmid = {29441527}, issn = {1558-5646}, abstract = {Studying the macroevolution of the songs of Passeriformes (perching birds) has proved challenging. The complexity of the task stems not just from the macroevolutionary and macroecological challenge of modeling so many species, but also from the difficulty in collecting and quantifying birdsong itself. Using machine learning techniques, we extracted songs from a large citizen science dataset, and then analyzed the evolution, and biotic and abiotic predictors of variation in birdsong across 578 passerine species. Contrary to expectations, we found few links between life-history traits (monogamy and sexual dimorphism) and the evolution of song pitch (peak frequency) or song complexity (standard deviation of frequency). However, we found significant support for morphological constraints on birdsong, as reflected in a negative correlation between bird size and song pitch. We also found that broad-scale biogeographical and climate factors such as net primary productivity, temperature, and regional species richness were significantly associated with both the evolution and present-day distribution of bird song features. Our analysis integrates comparative and spatial modeling with newly developed data cleaning and curation tools, and suggests that evolutionary history, morphology, and present-day ecological processes shape the distribution of song diversity in these charismatic and important birds.}, } @article {pmid29441526, year = {2018}, author = {Keller, IS and Bayer, T and Salzburger, W and Roth, O}, title = {Effects of parental care on resource allocation into immune defense and buccal microbiota in mouthbrooding cichlid fishes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {5}, pages = {1109-1123}, doi = {10.1111/evo.13452}, pmid = {29441526}, issn = {1558-5646}, abstract = {Sexual dimorphism is founded upon a resource allocation trade-off between investments in reproduction versus other life-history traits including the immune system. In species with conventional parental care roles, theory predicts that males maximize their lifetime reproductive success by allocating resources toward sexual selection, while females achieve this through prolonging their lifespan. Here, we examine the interrelation between sexual dimorphism and parental care strategies in closely related maternal and biparental mouthbrooding cichlid fishes from East African Lake Tanganyika. We measured cellular immune parameters, examined the relative expression of 28 immune system and life history-related candidate genes and analyzed the microbiota composition in the buccal cavity. According to our predictions, maternal mouthbrooders are more sexually dimorphic in immune parameters than biparental mouthbrooders, which has possibly arisen through a differential resource allocation into parental care versus secondary sexual traits. Biparental mouthbrooders, on the other hand, which share the costs of parental care, feature an upregulated adaptive immune response and stronger antiviral properties, while their inflammation response is reduced. Overall, our results suggest a differential resource allocation trade-off between the two modes of parental investment.}, } @article {pmid29440750, year = {2018}, author = {Costea, PI and Hildebrand, F and Arumugam, M and Bäckhed, F and Blaser, MJ and Bushman, FD and de Vos, WM and Ehrlich, SD and Fraser, CM and Hattori, M and Huttenhower, C and Jeffery, IB and Knights, D and Lewis, JD and Ley, RE and Ochman, H and O'Toole, PW and Quince, C and Relman, DA and Shanahan, F and Sunagawa, S and Wang, J and Weinstock, GM and Wu, GD and Zeller, G and Zhao, L and Raes, J and Knight, R and Bork, P}, title = {Publisher Correction: Enterotypes in the landscape of gut microbial community composition.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {388}, doi = {10.1038/s41564-018-0114-x}, pmid = {29440750}, issn = {2058-5276}, abstract = {In the version of this Perspective originally published, the first and last name of co-author Manimozhiyan Arumugam were switched. This has now been corrected in all versions of the Perspective.}, } @article {pmid29440749, year = {2018}, author = {Swidergall, M and Solis, NV and Lionakis, MS and Filler, SG}, title = {Publisher Correction: EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {387}, doi = {10.1038/s41564-017-0100-8}, pmid = {29440749}, issn = {2058-5276}, abstract = {In the version of this Article originally published, technical problems led to errors in Figs. 2d and 5b. In the western blot panel in Fig. 2d, actin bands were misaligned at the bottom of the image and did not line up with the other bands in the panel; the corrected figure is shown below. In Fig. 5b, the upper right panel had an incorrect title of 'CXCL3/KC'; it should have instead been 'CXCL1/KC'. These errors have now been corrected in all versions of the Article.}, } @article {pmid29440744, year = {2018}, author = {Timpson, NJ and Greenwood, CMT and Soranzo, N and Lawson, DJ and Richards, JB}, title = {Heritable contributions versus genetic architecture.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {185}, pmid = {29440744}, issn = {1471-0064}, support = {G9815508//Medical Research Council/United Kingdom ; MC_PC_15018//Medical Research Council/United Kingdom ; }, } @article {pmid29440743, year = {2018}, author = {Evans, LM and Keller, MC}, title = {Using partitioned heritability methods to explore genetic architecture.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {185}, pmid = {29440743}, issn = {1471-0064}, } @article {pmid29440742, year = {2018}, author = {Burgess, DJ}, title = {Genomics: Next regeneration sequencing for reference genomes.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {125}, pmid = {29440742}, issn = {1471-0064}, } @article {pmid29440723, year = {2018}, author = {Olley, G and Ansari, M and Bengani, H and Grimes, GR and Rhodes, J and von Kriegsheim, A and Blatnik, A and Stewart, FJ and Wakeling, E and Carroll, N and Ross, A and Park, SM and Bickmore, WA and Pradeepa, MM and FitzPatrick, DR and , }, title = {Publisher Correction: BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {767}, doi = {10.1038/s41588-018-0069-0}, pmid = {29440723}, issn = {1546-1718}, abstract = {In the version of this article initially published, Wendy Bickmore and Madapura Pradeepa were incorrectly not indicated as corresponding authors. The error has been corrected in the HTML and PDF versions of the paper.}, } @article {pmid29440716, year = {2018}, author = {Rolland, J and Silvestro, D and Schluter, D and Guisan, A and Broenniman, O and Salamin, N}, title = {Publisher Correction: The impact of endothermy on the climatic niche evolution and the distribution of vertebrate diversity.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {578}, doi = {10.1038/s41559-018-0492-8}, pmid = {29440716}, issn = {2397-334X}, abstract = {In the version of this Article originally published, in Fig. 3a the first boundary was incorrectly labelled the "K/T boundary"; it should have read the "K/Pg boundary". The two equations in the main text were incorrectly omitted from the HTML. In the description of the posterior distribution of an ancestral state, the normal distribution was incorrectly described as being "assigned as prior to the node value"; it should have read "assigned as calibration to the node value". In the associated equation (the second equation in the text), the denominator of the last term was incorrectly given as "Node prior"; it should have read "Node calibration". In the same equation, the numerator of the third term on the right-hand side of the equation contained incorrect superscript notation on the x and this is shown in the full equation in the notice below.In the Acknowledgements, the following two sentences were incorrectly omitted: "The authors thank the Vital-IT facilities of the Swiss Institute of Bioinformatics for the computational support" and "This work was funded by the University of Lausanne and the Swiss National Science Foundation (CRSIII3-147630) to N.S." In the Author contributions section, the first sentence was incorrectly given as "J.R. designed the study. J.R., N.S. and D. Silvestro designed the methodology and ran the analyses"; it should have read "J.R., D.S. and N.S. designed the study and the methodology". In the Supplementary Information, all three instances of the word "prior" were incorrect and should have read "calibration".These errors have now been corrected in all versions of the Article.}, } @article {pmid29440530, year = {2018}, author = {Kolodny, O and Feldman, MW and Creanza, N}, title = {Bridging cultural gaps: interdisciplinary studies in human cultural evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, doi = {10.1098/rstb.2017.0413}, pmid = {29440530}, issn = {1471-2970}, mesh = {*Cultural Evolution ; Humans ; Interdisciplinary Research ; }, } @article {pmid29440529, year = {2018}, author = {Feldman, MW and Ramachandran, S}, title = {Missing compared to what? Revisiting heritability, genes and culture.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440529}, issn = {1471-2970}, mesh = {*Cultural Evolution ; *Heredity ; Humans ; *Models, Genetic ; Models, Statistical ; Phenotype ; }, abstract = {Standard models for the determination of phenotypes from genes are grounded in simple assumptions that are inherent in the modern evolutionary synthesis (MES), which was developed in the 1930s, 1940s and 1950s. The MES was framed in the context of Mendelian genetic transmission enhanced by the Fisherian view of the way discretely inherited genes determine continuously quantitative phenotypes. The statistical models that are used to estimate and interpret genetic contributions to human phenotypes-including behavioural traits-are constructed within the framework of the MES. Variance analysis constitutes the main tool and is used under this framework to characterize genetic inheritance, and hence determination of phenotypes. In this essay, we show that cultural inheritance, when incorporated into models for the determination of phenotypes, can sharply reduce estimates of the genetic contribution to these phenotypes. Recognition of the importance of non-genetic transmission of many human traits is becoming ever more necessary to prevent regression to the debates of the 1970s and 1980s concerning policies based on genetic determination of complex human phenotypes.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440528, year = {2018}, author = {Fogarty, L}, title = {Cultural complexity and evolution in fluctuating environments.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440528}, issn = {1471-2970}, mesh = {*Cultural Diversity ; *Cultural Evolution ; *Environment ; Humans ; Learning ; Models, Theoretical ; Social Behavior ; }, abstract = {The effect of environmental change on the rate of innovation and level of cultural complexity in a population is a theoretically understudied piece of an important puzzle at the heart of cultural evolution. Many mathematical models of cultural complexity have focused on the role of demographic factors such as population size or density. However, statistical studies often point to environmental variability as an important factor determining complexity in many cases. The aim of this study is to explore the interaction between environmental fluctuations and the rate of cultural innovation within a population and to examine the relationship between rates of innovation and the probability of maintaining a complex cultural repertoire in a changing environment. Two models are presented that draw on previous models used to examine rates of genetic mutation. The models show that, as in a genetic system, the stable rate of cultural innovation in a population decreases with environmental stability and increases in unstable environments. This effect is similar but quantitatively different for different modes of cultural transmission (success bias, conformity bias and random oblique learning). The model shows that innovation can increase diversity but that this relationship depends critically on learning mode and learning parameters.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440527, year = {2018}, author = {Derex, M and Perreault, C and Boyd, R}, title = {Divide and conquer: intermediate levels of population fragmentation maximize cultural accumulation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440527}, issn = {1471-2970}, mesh = {*Cultural Diversity ; *Cultural Evolution ; Humans ; Models, Theoretical ; *Population Density ; }, abstract = {Identifying the determinants of cumulative cultural evolution is a key issue in the interdisciplinary field of cultural evolution. A widely held view is that large and well-connected social networks facilitate cumulative cultural evolution because they promote the spread of useful cultural traits and prevent the loss of cultural knowledge through factors such as drift. This view stems from models that focus on the transmission of cultural information, without considering how new cultural traits actually arise. In this paper, we review the literature from various fields that suggest that, under some circumstances, increased connectedness can decrease cultural diversity and reduce innovation rates. Incorporating this idea into an agent-based model, we explore the effect of population fragmentation on cumulative culture and show that, for a given population size, there exists an intermediate level of population fragmentation that maximizes the rate of cumulative cultural evolution. This result is explained by the fact that fully connected, non-fragmented populations are able to maintain complex cultural traits but produce insufficient variation and so lack the cultural diversity required to produce highly complex cultural traits. Conversely, highly fragmented populations produce a variety of cultural traits but cannot maintain complex ones. In populations with intermediate levels of fragmentation, cultural loss and cultural diversity are balanced in a way that maximizes cultural complexity. Our results suggest that population structure needs to be taken into account when investigating the relationship between demography and cumulative culture.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440526, year = {2018}, author = {Aoki, K}, title = {On the absence of a correlation between population size and 'toolkit size' in ethnographic hunter-gatherers.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440526}, issn = {1471-2970}, mesh = {Anthropology, Cultural ; *Cultural Evolution ; Humans ; *Life Style ; Models, Biological ; *Population Density ; }, abstract = {In apparent contradiction to the theoretically predicted effect of population size on the quality/quantity of material culture, statistical analyses on ethnographic hunter-gatherers have shown an absence of correlation between population size and toolkit size. This has sparked a heated, if sometimes tangential, debate as to the usefulness of the theoretical models and as to what modes of cultural transmission humans are capable of and hunter-gatherers rely on. I review the directly relevant theoretical literature and argue that much of the confusion is caused by a mismatch between the theoretical variable and the empirical observable. I then confirm that a model incorporating the appropriate variable does predict a positive association between population size and toolkit size for random oblique, vertical, best-of-K, conformist, anticonformist, success bias and one-to-many cultural transmission, with the caveat that for all populations sampled, the population size has remained constant and toolkit size has reached the equilibrium for this population size. Finally, I suggest three theoretical scenarios, two of them involving variable population size, that would attenuate or eliminate this association and hence help to explain the empirical absence of correlation.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440525, year = {2018}, author = {Mattison, S and Moya, C and Reynolds, A and Towner, MC}, title = {Evolutionary demography of age at last birth: integrating approaches from human behavioural ecology and cultural evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440525}, issn = {1471-2970}, mesh = {Age Distribution ; Biological Evolution ; *Cultural Evolution ; Demography ; *Fertility ; Humans ; Parturition/ethnology/*physiology/*psychology ; *Reproduction ; Reproductive Behavior ; }, abstract = {Cultural evolutionary theory and human behavioural ecology offer different, but compatible approaches to understanding human demographic behaviour. For much of their 30 history, these approaches have been deployed in parallel, with few explicit attempts to integrate them empirically. In this paper, we test hypotheses drawn from both approaches to explore how reproductive behaviour responds to cultural changes among Mosuo agriculturalists of China. Specifically, we focus on how age at last birth (ALB) varies in association with temporal shifts in fertility policies, spatial variation and kinship ecologies. We interpret temporal declines in ALB as plausibly consistent with demographic front-loading of reproduction in light of fertility constraints and later ages at last birth in matrilineal populations relative to patrilineal ones as consistent with greater household cooperation for reproductive purposes in the former. We find little evidence suggesting specific transmission pathways for the spread of norms regulating ALB, but emphasize that the rapid pace of change strongly suggests that learning processes were involved in the general decline in ALB over time. The different predictions of models we employ belie their considerable overlap and the potential for a synthetic approach to generate more refined tests of evolutionary hypotheses of demographic behaviour.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440524, year = {2018}, author = {Kline, MA and Shamsudheen, R and Broesch, T}, title = {Variation is the universal: making cultural evolution work in developmental psychology.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440524}, issn = {1471-2970}, mesh = {*Cross-Cultural Comparison ; *Cultural Evolution ; Humans ; *Psychology, Developmental ; }, abstract = {Culture is a human universal, yet it is a source of variation in human psychology, behaviour and development. Developmental researchers are now expanding the geographical scope of research to include populations beyond relatively wealthy Western communities. However, culture and context still play a secondary role in the theoretical grounding of developmental psychology research, far too often. In this paper, we highlight four false assumptions that are common in psychology, and that detract from the quality of both standard and cross-cultural research in development. These assumptions are: (i) the universality assumption, that empirical uniformity is evidence for universality, while any variation is evidence for culturally derived variation; (ii) the Western centrality assumption, that Western populations represent a normal and/or healthy standard against which development in all societies can be compared; (iii) the deficit assumption, that population-level differences in developmental timing or outcomes are necessarily due to something lacking among non-Western populations; and (iv) the equivalency assumption, that using identical research methods will necessarily produce equivalent and externally valid data, across disparate cultural contexts. For each assumption, we draw on cultural evolutionary theory to critique and replace the assumption with a theoretically grounded approach to culture in development. We support these suggestions with positive examples drawn from research in development. Finally, we conclude with a call for researchers to take reasonable steps towards more fully incorporating culture and context into studies of development, by expanding their participant pools in strategic ways. This will lead to a more inclusive and therefore more accurate description of human development.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440523, year = {2018}, author = {Garvey, R}, title = {Current and potential roles of archaeology in the development of cultural evolutionary theory.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440523}, issn = {1471-2970}, mesh = {*Archaeology ; *Cultural Evolution ; Humans ; Models, Biological ; Southwestern United States ; }, abstract = {Archaeology has much to contribute to the study of cultural evolution. Empirical data at archaeological timescales are uniquely well suited to tracking rates of cultural change, detecting phylogenetic signals among groups of artefacts, and recognizing long-run effects of distinct cultural transmission mechanisms. Nonetheless, these are still relatively infrequent subjects of archaeological analysis and archaeology's potential to help advance our understanding of cultural evolution has thus far been largely unrealized. Cultural evolutionary models developed in other fields have been used to interpret patterns identified in archaeological records, which in turn provides independent tests of these models' predictions, as demonstrated here through a study of late Prehistoric stone projectile points from the US Southwest. These tests may not be straightforward, though, because archaeological data are complex, often representing events aggregated over many years (or centuries or millennia), while processes thought to drive cultural evolution (e.g. biased learning) operate on much shorter timescales. To fulfil archaeology's potential, we should continue to develop models specifically tailored to archaeological circumstances, and explore ways to incorporate the rich contextual data produced by archaeological research.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440522, year = {2018}, author = {Kandler, A and Powell, A}, title = {Generative inference for cultural evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440522}, issn = {1471-2970}, mesh = {*Cultural Evolution ; Humans ; *Learning ; Models, Biological ; Social Learning ; }, abstract = {One of the major challenges in cultural evolution is to understand why and how various forms of social learning are used in human populations, both now and in the past. To date, much of the theoretical work on social learning has been done in isolation of data, and consequently many insights focus on revealing the learning processes or the distributions of cultural variants that are expected to have evolved in human populations. In population genetics, recent methodological advances have allowed a greater understanding of the explicit demographic and/or selection mechanisms that underlie observed allele frequency distributions across the globe, and their change through time. In particular, generative frameworks-often using coalescent-based simulation coupled with approximate Bayesian computation (ABC)-have provided robust inferences on the human past, with no reliance on a priori assumptions of equilibrium. Here, we demonstrate the applicability and utility of generative inference approaches to the field of cultural evolution. The framework advocated here uses observed population-level frequency data directly to establish the likely presence or absence of particular hypothesized learning strategies. In this context, we discuss the problem of equifinality and argue that, in the light of sparse cultural data and the multiplicity of possible social learning processes, the exclusion of those processes inconsistent with the observed data might be the most instructive outcome. Finally, we summarize the findings of generative inference approaches applied to a number of case studies.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440521, year = {2018}, author = {Sherriah, AC and Devonish, H and Thomas, EAC and Creanza, N}, title = {Using features of a Creole language to reconstruct population history and cultural evolution: tracing the English origins of Sranan.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440521}, issn = {1471-2970}, mesh = {*Cultural Evolution ; England ; Humans ; *Language ; *Linguistics ; Phylogeny ; Suriname ; }, abstract = {Creole languages are formed in conditions where speakers from distinct languages are brought together without a shared first language, typically under the domination of speakers from one of the languages and particularly in the context of the transatlantic slave trade and European colonialism. One such Creole in Suriname, Sranan, developed around the mid-seventeenth century, primarily out of contact between varieties of English from England, spoken by the dominant group, and multiple West African languages. The vast majority of the basic words in Sranan come from the language of the dominant group, English. Here, we compare linguistic features of modern-day Sranan with those of English as spoken in 313 localities across England. By way of testing proposed hypotheses for the origin of English words in Sranan, we find that 80% of the studied features of Sranan can be explained by similarity to regional dialect features at two distinct input locations within England, a cluster of locations near the port of Bristol and another cluster near Essex in eastern England. Our new hypothesis is supported by the geographical distribution of specific regional dialect features, such as post-vocalic rhoticity and word-initial 'h', and by phylogenetic analysis of these features, which shows evidence favouring input from at least two English dialects in the formation of Sranan. In addition to explicating the dialect features most prominent in the linguistic evolution of Sranan, our historical analyses also provide supporting evidence for two distinct hypotheses about the likely geographical origins of the English speakers whose language was an input to Sranan. The emergence as a likely input to Sranan of the speech forms of a cluster near Bristol is consistent with historical records, indicating that most of the indentured servants going to the Americas between 1654 and 1666 were from Bristol and nearby counties, and that of the cluster near Essex is consistent with documents showing that many of the governors and important planters came from the southeast of England (including London) (Smith 1987 The Genesis of the Creole Languages of Surinam; Smith 2009 In The handbook of pidgin and creole studies, pp. 98-129).This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440520, year = {2018}, author = {von Cramon-Taubadel, N and Lycett, SJ}, title = {Assessing the relative impact of historical divergence and inter-group transmission on cultural patterns: a method from evolutionary ecology.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440520}, issn = {1471-2970}, mesh = {*Cephalometry ; *Cultural Evolution ; Ecology/*methods ; Humans ; New Guinea ; }, abstract = {In the study of cultural evolution, observed among-group affinity patterns reflect the effects of processes such as mutation (e.g. innovation and copying error), between-group interaction (culture flow), drift and selection. As in biology, cultural affinity patterns are often spatially correlated, making it difficult to distinguish between the opposing geographically mediated forces of divergence and interaction, which cause groups to become more distinct or similar over time, respectively. Analogous difficulties are faced by evolutionary biologists examining the relationship between biological affinity and geography, particularly at lower taxonomic levels where the potential for gene flow between lineages is greatest. Tree models are generally used to assess the fit between affinity patterns and models of historical divergence. However, factors driving lineage divergence are often spatially mediated, resulting in tree models that are themselves geographically structured. Here, we showcase a simple method drawn from evolutionary ecology for assessing the relative impact of both geographically mediated processes simultaneously. We illustrate the method using global human craniometric diversity and material culture from the northern coast of New Guinea as example case studies. This method can be employed to quantify the relative importance of history (divergence) and geographically mediated between-group interaction (culture flow) in explaining observed cultural affinity patterns.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440519, year = {2018}, author = {Arbilly, M}, title = {High-magnitude innovators as keystone individuals in the evolution of culture.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440519}, issn = {1471-2970}, mesh = {Animals ; *Behavior, Animal ; Computer Simulation ; Creativity ; *Cultural Evolution ; *Diffusion of Innovation ; Models, Psychological ; }, abstract = {Borrowing from the concept of keystone species in ecological food webs, a recent focus in the field of animal behaviour has been keystone individuals: individuals whose impact on population dynamics is disproportionally larger than their frequency in the population. In populations evolving culture, such may be the role of high-magnitude innovators: individuals whose innovations are a major departure from the population's existing behavioural repertoire. Their effect on cultural evolution is twofold: they produce innovations that constitute a 'cultural leap' and, once copied, their innovations may induce further innovations by conspecifics (socially induced innovations) as they explore the new behaviour themselves. I use computer simulations to study the coevolution of independent innovations, socially induced innovations and innovation magnitude, and show that while socially induced innovation is assumed here to be less costly than independent innovation, it does not readily evolve. When it evolves, it may in some conditions select against independent innovation and lower its frequency, despite it requiring independent innovation in order to operate; at the same time, however, it leads to much faster cultural evolution. These results confirm the role of high-magnitude innovators as keystones, and suggest a novel explanation for the low frequency of independent innovation.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440518, year = {2018}, author = {Kolodny, O and Edelman, S}, title = {The evolution of the capacity for language: the ecological context and adaptive value of a process of cognitive hijacking.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440518}, issn = {1471-2970}, mesh = {Adaptation, Physiological ; Animals ; *Cognition ; *Cultural Evolution ; Hominidae/*psychology ; Humans ; *Language ; }, abstract = {Language plays a pivotal role in the evolution of human culture, yet the evolution of the capacity for language-uniquely within the hominin lineage-remains little understood. Bringing together insights from cognitive psychology, neuroscience, archaeology and behavioural ecology, we hypothesize that this singular occurrence was triggered by exaptation, or 'hijacking', of existing cognitive mechanisms related to sequential processing and motor execution. Observed coupling of the communication system with circuits related to complex action planning and control supports this proposition, but the prehistoric ecological contexts in which this coupling may have occurred and its adaptive value remain elusive. Evolutionary reasoning rules out most existing hypotheses regarding the ecological context of language evolution, which focus on ultimate explanations and ignore proximate mechanisms. Coupling of communication and motor systems, although possible in a short period on evolutionary timescales, required a multi-stepped adaptive process, involving multiple genes and gene networks. We suggest that the behavioural context that exerted the selective pressure to drive these sequential adaptations had to be one in which each of the systems undergoing coupling was independently necessary or highly beneficial, as well as frequent and recurring over evolutionary time. One such context could have been the teaching of tool production or tool use. In the present study, we propose the Cognitive Coupling hypothesis, which brings together these insights and outlines a unifying theory for the evolution of the capacity for language.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440517, year = {2018}, author = {Heyes, C}, title = {Enquire within: cultural evolution and cognitive science.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440517}, issn = {1471-2970}, mesh = {Cognitive Science ; Cultural Evolution ; Humans ; *Social Learning ; }, abstract = {Cultural evolution and cognitive science need each other. Cultural evolution needs cognitive science to find out whether the conditions necessary for Darwinian evolution are met in the cultural domain. Cognitive science needs cultural evolution to explain the origins of distinctively human cognitive processes. Focusing on the first question, I argue that cultural evolutionists can get empirical traction on third-way cultural selection by rooting the distinction between replication and reconstruction, two modes of cultural inheritance, in the distinction between System 1 and System 2 cognitive processes. This move suggests that cultural epidemiologists are right in thinking that replication has higher fidelity than reconstruction, and replication processes are not genetic adaptations for culture, but wrong to assume that replication is rare. If replication is not rare, an important requirement for third-way cultural selection, one-shot fidelity, is likely to be met. However, there are other requirements, overlooked by dual-inheritance theorists when they conflate strong (Darwinian) and weak (choice) senses of 'cultural selection', including dumb choices and recurrent fidelity In a second excursion into cognitive science, I argue that these requirements can be met by metacognitive social learning strategies, and trace the origins of these distinctively human cognitive processes to cultural evolution. Like other forms of cultural learning, they are not cognitive instincts but cognitive gadgets.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440516, year = {2018}, author = {Truskanov, N and Prat, Y}, title = {Cultural transmission in an ever-changing world: trial-and-error copying may be more robust than precise imitation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440516}, issn = {1471-2970}, mesh = {*Cultural Evolution ; Humans ; *Imitative Behavior ; *Social Learning ; }, abstract = {Cultural transmission facilitates the spread of behaviours within social groups and may lead to the establishment of stable traditions in both human and non-human animals. The fidelity of transmission is frequently emphasized as a core component of cultural evolution and as a prerequisite for cumulative culture. Fidelity is often considered a synonym of precise copying of observed behaviours. However, while precise copying guarantees reliable transmission in an ideal static world, it may be vulnerable to realistic variability in the actual environment. Here, we argue that fidelity may be more naturally achieved when the social learning mechanisms incorporate trial-and-error; and that the robustness of social transmission is thereby increased. We employed a simple model to demonstrate how culture that is produced through exact copying is fragile in an (even slightly) noisy world. When incorporating a certain degree of trial-and-error, however, cultures are more readily formed in a stochastic environment and are less vulnerable to rare ecological changes. We suggest that considering trial-and-error learning as a stabilizing component of social transmission may provide insights into cultural evolution in a realistic, variable, world.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440515, year = {2018}, author = {Kolodny, O and Feldman, MW and Creanza, N}, title = {Integrative studies of cultural evolution: crossing disciplinary boundaries to produce new insights.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1743}, pages = {}, pmid = {29440515}, issn = {1471-2970}, mesh = {*Cultural Evolution ; Humans ; Interdisciplinary Research ; }, abstract = {Culture evolves according to dynamics on multiple temporal scales, from individuals' minute-by-minute behaviour to millennia of cultural accumulation that give rise to population-level differences. These dynamics act on a range of entities-including behavioural sequences, ideas and artefacts as well as individuals, populations and whole species-and involve mechanisms at multiple levels, from neurons in brains to inter-population interactions. Studying such complex phenomena requires an integration of perspectives from a diverse array of fields, as well as bridging gaps between traditionally disparate areas of study. In this article, which also serves as an introduction to the current special issue, we highlight some specific respects in which the study of cultural evolution has benefited and should continue to benefit from an integrative approach. We showcase a number of pioneering studies of cultural evolution that bring together numerous disciplines. These studies illustrate the value of perspectives from different fields for understanding cultural evolution, such as cognitive science and neuroanatomy, behavioural ecology, population dynamics, and evolutionary genetics. They also underscore the importance of understanding cultural processes when interpreting research about human genetics, neuroscience, behaviour and evolution.This article is part of the theme issue 'Bridging cultural gaps: interdisciplinary studies in human cultural evolution'.}, } @article {pmid29440500, year = {2018}, author = {Wannier, TM and Kunjapur, AM and Rice, DP and McDonald, MJ and Desai, MM and Church, GM}, title = {Adaptive evolution of genomically recoded Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3090-3095}, pmid = {29440500}, issn = {1091-6490}, mesh = {Adaptation, Physiological/*genetics ; *Biological Evolution ; DNA, Bacterial ; Escherichia coli/*genetics/*physiology ; Escherichia coli Proteins/genetics/*metabolism ; Gene Expression Regulation, Bacterial/physiology ; *Genetic Engineering ; Genome, Bacterial ; Mutation ; }, abstract = {Efforts are underway to construct several recoded genomes anticipated to exhibit multivirus resistance, enhanced nonstandard amino acid (nsAA) incorporation, and capability for synthetic biocontainment. Although our laboratory pioneered the first genomically recoded organism (Escherichia coli strain C321.∆A), its fitness is far lower than that of its nonrecoded ancestor, particularly in defined media. This fitness deficit severely limits its utility for nsAA-linked applications requiring defined media, such as live cell imaging, metabolic engineering, and industrial-scale protein production. Here, we report adaptive evolution of C321.∆A for more than 1,000 generations in independent replicate populations grown in glucose minimal media. Evolved recoded populations significantly exceeded the growth rates of both the ancestral C321.∆A and nonrecoded strains. We used next-generation sequencing to identify genes mutated in multiple independent populations, and we reconstructed individual alleles in ancestral strains via multiplex automatable genome engineering (MAGE) to quantify their effects on fitness. Several selective mutations occurred only in recoded evolved populations, some of which are associated with altering the translation apparatus in response to recoding, whereas others are not apparently associated with recoding, but instead correct for off-target mutations that occurred during initial genome engineering. This report demonstrates that laboratory evolution can be applied after engineering of recoded genomes to streamline fitness recovery compared with application of additional targeted engineering strategies that may introduce further unintended mutations. In doing so, we provide the most comprehensive insight to date into the physiology of the commonly used C321.∆A strain.}, } @article {pmid29440499, year = {2018}, author = {Melnyk, CW and Gabel, A and Hardcastle, TJ and Robinson, S and Miyashima, S and Grosse, I and Meyerowitz, EM}, title = {Transcriptome dynamics at Arabidopsis graft junctions reveal an intertissue recognition mechanism that activates vascular regeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2447-E2456}, pmid = {29440499}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Breeding ; Gene Expression Regulation, Plant ; Indoleacetic Acids/metabolism ; Plant Vascular Bundle/genetics/*physiology ; Regeneration ; Transcriptome ; }, abstract = {The ability for cut tissues to join and form a chimeric organism is a remarkable property of many plants; however, grafting is poorly characterized at the molecular level. To better understand this process, we monitored genome-wide gene expression changes in grafted Arabidopsis thaliana hypocotyls. We observed a sequential activation of genes associated with cambium, phloem, and xylem formation. Tissues above and below the graft rapidly developed an asymmetry such that many genes were more highly expressed on one side than on the other. This asymmetry correlated with sugar-responsive genes, and we observed an accumulation of starch above the graft junction. This accumulation decreased along with asymmetry once the sugar-transporting vascular tissues reconnected. Despite the initial starvation response below the graft, many genes associated with vascular formation were rapidly activated in grafted tissues but not in cut and separated tissues, indicating that a recognition mechanism was activated independently of functional vascular connections. Auxin, which is transported cell to cell, had a rapidly elevated response that was symmetric, suggesting that auxin was perceived by the root within hours of tissue attachment to activate the vascular regeneration process. A subset of genes was expressed only in grafted tissues, indicating that wound healing proceeded via different mechanisms depending on the presence or absence of adjoining tissues. Such a recognition process could have broader relevance for tissue regeneration, intertissue communication, and tissue fusion events.}, } @article {pmid29440498, year = {2018}, author = {Alam, A and Küng, R and Kowal, J and McLeod, RA and Tremp, N and Broude, EV and Roninson, IB and Stahlberg, H and Locher, KP}, title = {Structure of a zosuquidar and UIC2-bound human-mouse chimeric ABCB1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1973-E1982}, pmid = {29440498}, issn = {1091-6490}, support = {P20 GM109091/GM/NIGMS NIH HHS/United States ; }, mesh = {ATP Binding Cassette Transporter, Subfamily B/chemistry ; ATP Binding Cassette Transporter, Subfamily B, Member 1/*chemistry ; Adenosine Triphosphatases/chemistry ; Animals ; Antibodies/*chemistry ; Cross-Linking Reagents/chemistry ; Cryoelectron Microscopy ; Dibenzocycloheptenes/*chemistry ; Epitopes/chemistry ; HEK293 Cells ; Humans ; Ligands ; Mice ; Molecular Conformation ; Mutation ; Protein Binding ; Protein Conformation ; Quinolines/*chemistry ; }, abstract = {The multidrug transporter ABCB1 (P-glycoprotein) is an ATP-binding cassette transporter that has a key role in protecting tissues from toxic insult and contributes to multidrug extrusion from cancer cells. Here, we report the near-atomic resolution cryo-EM structure of nucleotide-free ABCB1 trapped by an engineered disulfide cross-link between the nucleotide-binding domains (NBDs) and bound to the antigen-binding fragment of the human-specific inhibitory antibody UIC2 and to the third-generation ABCB1 inhibitor zosuquidar. Our structure reveals the transporter in an occluded conformation with a central, enclosed, inhibitor-binding pocket lined by residues from all transmembrane (TM) helices of ABCB1. The pocket spans almost the entire width of the lipid membrane and is occupied exclusively by two closely interacting zosuquidar molecules. The external, conformational epitope facilitating UIC2 binding is also visualized, providing a basis for its inhibition of substrate efflux. Additional cryo-EM structures suggest concerted movement of TM helices from both halves of the transporters associated with closing the NBD gap, as well as zosuquidar binding. Our results define distinct recognition interfaces of ABCB1 inhibitory agents, which may be exploited for therapeutic purposes.}, } @article {pmid29440497, year = {2018}, author = {Lonhienne, T and Garcia, MD and Pierens, G and Mobli, M and Nouwens, A and Guddat, LW}, title = {Structural insights into the mechanism of inhibition of AHAS by herbicides.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1945-E1954}, pmid = {29440497}, issn = {1091-6490}, mesh = {Acetolactate Synthase/*antagonists & inhibitors/*chemistry ; Arabidopsis/enzymology ; Catalysis ; Catalytic Domain ; Crystallography, X-Ray ; Herbicides/*chemistry ; Models, Molecular ; Oxygen/*chemistry ; Protein Binding ; Reactive Oxygen Species/*chemistry ; Saccharomyces cerevisiae/enzymology ; Temperature ; Thiamine Pyrophosphate/chemistry ; }, abstract = {Acetohydroxyacid synthase (AHAS), the first enzyme in the branched amino acid biosynthesis pathway, is present only in plants and microorganisms, and it is the target of >50 commercial herbicides. Penoxsulam (PS), which is a highly effective broad-spectrum AHAS-inhibiting herbicide, is used extensively to control weed growth in rice crops. However, the molecular basis for its inhibition of AHAS is poorly understood. This is despite the availability of structural data for all other classes of AHAS-inhibiting herbicides. Here, crystallographic data for Saccharomyces cerevisiae AHAS (2.3 Å) and Arabidopsis thaliana AHAS (2.5 Å) in complex with PS reveal the extraordinary molecular mechanisms that underpin its inhibitory activity. The structures show that inhibition of AHAS by PS triggers expulsion of two molecules of oxygen bound in the active site, releasing them as substrates for an oxygenase side reaction of the enzyme. The structures also show that PS either stabilizes the thiamin diphosphate (ThDP)-peracetate adduct, a product of this oxygenase reaction, or traps within the active site an intact molecule of peracetate in the presence of a degraded form of ThDP: thiamine aminoethenethiol diphosphate. Kinetic analysis shows that PS inhibits AHAS by a combination of events involving FAD oxidation and chemical alteration of ThDP. With the emergence of increasing levels of resistance toward front-line herbicides and the need to optimize the use of arable land, these data suggest strategies for next generation herbicide design.}, } @article {pmid29440496, year = {2018}, author = {Lemos, BR and Kaplan, AC and Bae, JE and Ferrazzoli, AE and Kuo, J and Anand, RP and Waterman, DP and Haber, JE}, title = {CRISPR/Cas9 cleavages in budding yeast reveal templated insertions and strand-specific insertion/deletion profiles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2040-E2047}, pmid = {29440496}, issn = {1091-6490}, support = {R01 GM076020/GM/NIGMS NIH HHS/United States ; P01 GM105473/GM/NIGMS NIH HHS/United States ; R37 GM020056/GM/NIGMS NIH HHS/United States ; R01 GM020056/GM/NIGMS NIH HHS/United States ; T32 GM007122/GM/NIGMS NIH HHS/United States ; }, mesh = {*CRISPR-Cas Systems ; Chromosomes/*ultrastructure ; *DNA Breaks, Double-Stranded ; DNA End-Joining Repair ; DNA Ligase ATP/metabolism ; DNA Repair ; DNA-Binding Proteins/metabolism ; Dimerization ; Endonucleases/metabolism ; Gene Deletion ; *INDEL Mutation ; Ku Autoantigen ; Plasmids/metabolism ; Promoter Regions, Genetic ; *RNA, Guide ; Saccharomycetales/*genetics ; Sequence Analysis, DNA ; }, abstract = {Harnessing CRISPR-Cas9 technology provides an unprecedented ability to modify genomic loci via DNA double-strand break (DSB) induction and repair. We analyzed nonhomologous end-joining (NHEJ) repair induced by Cas9 in budding yeast and found that the orientation of binding of Cas9 and its guide RNA (gRNA) profoundly influences the pattern of insertion/deletions (indels) at the site of cleavage. A common indel created by Cas9 is a 1-bp (+1) insertion that appears to result from Cas9 creating a 1-nt 5' overhang that is filled in by a DNA polymerase and ligated. The origin of +1 insertions was investigated by using two gRNAs with PAM sequences located on opposite DNA strands but designed to cleave the same sequence. These templated +1 insertions are dependent on the X-family DNA polymerase, Pol4. Deleting Pol4 also eliminated +2 and +3 insertions, which are biased toward homonucleotide insertions. Using inverted PAM sequences, we also found significant differences in overall NHEJ efficiency and repair profiles, suggesting that the binding of the Cas9:gRNA complex influences subsequent NHEJ processing. As with events induced by the site-specific HO endonuclease, CRISPR-Cas9-mediated NHEJ repair depends on the Ku heterodimer and DNA ligase 4. Cas9 events are highly dependent on the Mre11-Rad50-Xrs2 complex, independent of Mre11's nuclease activity. Inspection of the outcomes of a large number of Cas9 cleavage events in mammalian cells reveals a similar templated origin of +1 insertions in human cells, but also a significant frequency of similarly templated +2 insertions.}, } @article {pmid29440495, year = {2018}, author = {Lu, P and Wang, J and Li, H and Lin, K and Gong, X and Song, Q and Ji, Q and Zhang, W and Ma, J and Li, H and Zeng, H and He, F and Wu, J}, title = {High-order above-threshold dissociation of molecules.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2049-2053}, pmid = {29440495}, issn = {1091-6490}, abstract = {Electrons bound to atoms or molecules can simultaneously absorb multiple photons via the above-threshold ionization featured with discrete peaks in the photoelectron spectrum on account of the quantized nature of the light energy. Analogously, the above-threshold dissociation of molecules has been proposed to address the multiple-photon energy deposition in the nuclei of molecules. In this case, nuclear energy spectra consisting of photon-energy spaced peaks exceeding the binding energy of the molecular bond are predicted. Although the observation of such phenomena is difficult, this scenario is nevertheless logical and is based on the fundamental laws. Here, we report conclusive experimental observation of high-order above-threshold dissociation of H2 in strong laser fields where the tunneling-ionized electron transfers the absorbed multiphoton energy, which is above the ionization threshold to the nuclei via the field-driven inelastic rescattering. Our results provide an unambiguous evidence that the electron and nuclei of a molecule as a whole absorb multiple photons, and thus above-threshold ionization and above-threshold dissociation must appear simultaneously, which is the cornerstone of the nowadays strong-field molecular physics.}, } @article {pmid29440494, year = {2018}, author = {Goettker, A and Braun, DI and Schütz, AC and Gegenfurtner, KR}, title = {Execution of saccadic eye movements affects speed perception.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2240-2245}, pmid = {29440494}, issn = {1091-6490}, mesh = {Adult ; Brain/physiology ; Female ; Fovea Centralis ; Humans ; Male ; Motion ; *Motion Perception ; Normal Distribution ; *Photic Stimulation ; Reproducibility of Results ; Retina/physiology ; Saccades/*physiology ; Young Adult ; }, abstract = {Due to the foveal organization of our visual system we have to constantly move our eyes to gain precise information about our environment. Doing so massively alters the retinal input. This is problematic for the perception of moving objects, because physical motion and retinal motion become decoupled and the brain has to discount the eye movements to recover the speed of moving objects. Two different types of eye movements, pursuit and saccades, are combined for tracking. We investigated how the way we track moving targets can affect the perceived target speed. We found that the execution of corrective saccades during pursuit initiation modifies how fast the target is perceived compared with pure pursuit. When participants executed a forward (catch-up) saccade they perceived the target to be moving faster. When they executed a backward saccade they perceived the target to be moving more slowly. Variations in pursuit velocity without corrective saccades did not affect perceptual judgments. We present a model for these effects, assuming that the eye velocity signal for small corrective saccades gets integrated with the retinal velocity signal during pursuit. In our model, the execution of corrective saccades modulates the integration of these two signals by giving less weight to the retinal information around the time of corrective saccades.}, } @article {pmid29440493, year = {2018}, author = {Gowda, SBM and Paranjpe, PD and Reddy, OV and Thiagarajan, D and Palliyil, S and Reichert, H and VijayRaghavan, K}, title = {GABAergic inhibition of leg motoneurons is required for normal walking behavior in freely moving Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2115-E2124}, pmid = {29440493}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; Animals, Genetically Modified ; Drosophila/*physiology ; Electromyography ; Electronic Data Processing ; Extremities/physiology ; Feedback, Sensory ; Immunohistochemistry ; Interneurons/physiology ; Introns ; Locomotion/*physiology ; Male ; Microscopy, Confocal ; Motor Neurons/*physiology ; Neurotransmitter Agents/physiology ; Periodicity ; Phenotype ; RNA Interference ; Signal Processing, Computer-Assisted ; Video Recording ; Walking/*physiology ; }, abstract = {Walking is a complex rhythmic locomotor behavior generated by sequential and periodical contraction of muscles essential for coordinated control of movements of legs and leg joints. Studies of walking in vertebrates and invertebrates have revealed that premotor neural circuitry generates a basic rhythmic pattern that is sculpted by sensory feedback and ultimately controls the amplitude and phase of the motor output to leg muscles. However, the identity and functional roles of the premotor interneurons that directly control leg motoneuron activity are poorly understood. Here we take advantage of the powerful genetic methodology available in Drosophila to investigate the role of premotor inhibition in walking by genetically suppressing inhibitory input to leg motoneurons. For this, we have developed an algorithm for automated analysis of leg motion to characterize the walking parameters of wild-type flies from high-speed video recordings. Further, we use genetic reagents for targeted RNAi knockdown of inhibitory neurotransmitter receptors in leg motoneurons together with quantitative analysis of resulting changes in leg movement parameters in freely walking Drosophila Our findings indicate that targeted down-regulation of the GABAA receptor Rdl (Resistance to Dieldrin) in leg motoneurons results in a dramatic reduction of walking speed and step length without the loss of general leg coordination during locomotion. Genetically restricting the knockdown to the adult stage and subsets of motoneurons yields qualitatively identical results. Taken together, these findings identify GABAergic premotor inhibition of motoneurons as an important determinant of correctly coordinated leg movements and speed of walking in freely behaving Drosophila.}, } @article {pmid29440492, year = {2018}, author = {Beyerlein, KR}, title = {Time-spliced X-ray diffraction imaging of magnetism dynamics in a NdNiO3 thin film.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2044-2048}, pmid = {29440492}, issn = {1091-6490}, support = {319286//European Research Council/International ; }, abstract = {Diffraction imaging of nonequilibrium dynamics at atomic resolution is becoming possible with X-ray free-electron lasers. However, there are unresolved problems with applying this method to objects that are confined in only one dimension. Here I show that reliable one-dimensional coherent diffraction imaging is possible by splicing together images recovered from different time delays in an optical pump X-ray probe experiment. The time and space evolution of antiferromagnetic order in a vibrationally excited complex oxide heterostructure is recovered from time-resolved measurements of a resonant soft X-ray diffraction peak. Midinfrared excitation of the substrate is shown to lead to a demagnetization front that propagates at a velocity exceeding the speed of sound, a critical observation for the understanding of driven phase transitions in complex condensed matter.}, } @article {pmid29440491, year = {2018}, author = {Usluer, GD and DiMaio, F and Yang, SK and Hansen, JM and Polka, JK and Mullins, RD and Kollman, JM}, title = {Cryo-EM structure of the bacterial actin AlfA reveals unique assembly and ATP-binding interactions and the absence of a conserved subdomain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3356-3361}, pmid = {29440491}, issn = {1091-6490}, support = {R01 GM123089/GM/NIGMS NIH HHS/United States ; 298465//CIHR/Canada ; }, mesh = {Actins/*metabolism/*ultrastructure ; Adenosine Triphosphate/*metabolism ; Amino Acid Sequence ; Bacterial Proteins/*metabolism/*ultrastructure ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Cytoskeleton/metabolism ; Models, Molecular ; Protein Domains ; Sequence Homology ; }, abstract = {Bacterial actins are an evolutionarily diverse family of ATP-dependent filaments built from protomers with a conserved structural fold. Actin-based segregation systems are encoded on many bacterial plasmids and function to partition plasmids into daughter cells. The bacterial actin AlfA segregates plasmids by a mechanism distinct from other partition systems, dependent on its unique dynamic properties. Here, we report the near-atomic resolution electron cryo-microscopy structure of the AlfA filament, which reveals a strikingly divergent filament architecture resulting from the loss of a subdomain conserved in all other actins and a mode of ATP binding. Its unusual assembly interfaces and nucleotide interactions provide insight into AlfA dynamics, and expand the range of evolutionary variation accessible to actin quaternary structure.}, } @article {pmid29440490, year = {2018}, author = {Kim, DS and Hellman, O and Herriman, J and Smith, HL and Lin, JYY and Shulumba, N and Niedziela, JL and Li, CW and Abernathy, DL and Fultz, B}, title = {Nuclear quantum effect with pure anharmonicity and the anomalous thermal expansion of silicon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1992-1997}, pmid = {29440490}, issn = {1091-6490}, abstract = {Despite the widespread use of silicon in modern technology, its peculiar thermal expansion is not well understood. Adapting harmonic phonons to the specific volume at temperature, the quasiharmonic approximation, has become accepted for simulating the thermal expansion, but has given ambiguous interpretations for microscopic mechanisms. To test atomistic mechanisms, we performed inelastic neutron scattering experiments from 100 K to 1,500 K on a single crystal of silicon to measure the changes in phonon frequencies. Our state-of-the-art ab initio calculations, which fully account for phonon anharmonicity and nuclear quantum effects, reproduced the measured shifts of individual phonons with temperature, whereas quasiharmonic shifts were mostly of the wrong sign. Surprisingly, the accepted quasiharmonic model was found to predict the thermal expansion owing to a large cancellation of contributions from individual phonons.}, } @article {pmid29440489, year = {2018}, author = {Szewczak-Harris, A and Löwe, J}, title = {Cryo-EM reconstruction of AlfA from Bacillus subtilis reveals the structure of a simplified actin-like filament at 3.4-Å resolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {13}, pages = {3458-3463}, pmid = {29440489}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MC_U105184326//Medical Research Council/United Kingdom ; 095514/Z/11/Z//Wellcome Trust/United Kingdom ; }, mesh = {Actin Cytoskeleton/metabolism/*ultrastructure ; Bacillus subtilis/*metabolism/*ultrastructure ; Bacterial Proteins/metabolism/*ultrastructure ; Cryoelectron Microscopy/*methods ; Crystallography, X-Ray ; Cytoskeleton/metabolism ; DNA, Bacterial ; Models, Molecular ; *Plasmids ; }, abstract = {Low copy-number plasmid pLS32 of Bacillus subtilis subsp. natto contains a partitioning system that ensures segregation of plasmid copies during cell division. The partitioning locus comprises actin-like protein AlfA, adaptor protein AlfB, and the centromeric sequence parN Similar to the ParMRC partitioning system from Escherichia coli plasmid R1, AlfA filaments form actin-like double helical filaments that arrange into an antiparallel bipolar spindle, which attaches its growing ends to sister plasmids through interactions with AlfB and parN Because, compared with ParM and other actin-like proteins, AlfA is highly diverged in sequence, we determined the atomic structure of nonbundling AlfA filaments to 3.4-Å resolution by cryo-EM. The structure reveals how the deletion of subdomain IIB of the canonical actin fold has been accommodated by unique longitudinal and lateral contacts, while still enabling formation of left-handed, double helical, polar and staggered filaments that are architecturally similar to ParM. Through cryo-EM reconstruction of bundling AlfA filaments, we obtained a pseudoatomic model of AlfA doublets: the assembly of two filaments. The filaments are antiparallel, as required by the segregation mechanism, and exactly antiphasic with near eightfold helical symmetry, to enable efficient doublet formation. The structure of AlfA filaments and doublets shows, in atomic detail, how deletion of an entire domain of the actin fold is compensated by changes to all interfaces so that the required properties of polymerization, nucleotide hydrolysis, and antiparallel doublet formation are retained to fulfill the system's biological raison d'être.}, } @article {pmid29440488, year = {2018}, author = {Janke, R and King, GA and Kupiec, M and Rine, J}, title = {Pivotal roles of PCNA loading and unloading in heterochromatin function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2030-E2039}, pmid = {29440488}, issn = {1091-6490}, support = {F32 GM115074/GM/NIGMS NIH HHS/United States ; R01 GM031105/GM/NIGMS NIH HHS/United States ; R01 GM120374/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; }, mesh = {Carrier Proteins/metabolism ; DNA Replication ; Gene Deletion ; *Gene Expression Regulation, Fungal ; Gene Silencing ; Genome, Fungal ; Heterochromatin/*metabolism ; Histones/metabolism ; Open Reading Frames ; Plasmids/metabolism ; Proliferating Cell Nuclear Antigen/*metabolism ; Ribonucleases/metabolism ; S Phase ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/*metabolism ; Transcription, Genetic ; }, abstract = {In Saccharomyces cerevisiae, heterochromatin structures required for transcriptional silencing of the HML and HMR loci are duplicated in coordination with passing DNA replication forks. Despite major reorganization of chromatin structure, the heterochromatic, transcriptionally silent states of HML and HMR are successfully maintained throughout S-phase. Mutations of specific components of the replisome diminish the capacity to maintain silencing of HML and HMR through replication. Similarly, mutations in histone chaperones involved in replication-coupled nucleosome assembly reduce gene silencing. Bridging these observations, we determined that the proliferating cell nuclear antigen (PCNA) unloading activity of Elg1 was important for coordinating DNA replication forks with the process of replication-coupled nucleosome assembly to maintain silencing of HML and HMR through S-phase. Collectively, these data identified a mechanism by which chromatin reassembly is coordinated with DNA replication to maintain silencing through S-phase.}, } @article {pmid29440487, year = {2018}, author = {Barbier, M and Arnoldi, JF and Bunin, G and Loreau, M}, title = {Generic assembly patterns in complex ecological communities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2156-2161}, pmid = {29440487}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; Computer Simulation ; *Genetic Variation ; *Models, Biological ; }, abstract = {The study of ecological communities often involves detailed simulations of complex networks. However, our empirical knowledge of these networks is typically incomplete and the space of simulation models and parameters is vast, leaving room for uncertainty in theoretical predictions. Here we show that a large fraction of this space of possibilities exhibits generic behaviors that are robust to modeling choices. We consider a wide array of model features, including interaction types and community structures, known to generate different dynamics for a few species. We combine these features in large simulated communities, and show that equilibrium diversity, functioning, and stability can be predicted analytically using a random model parameterized by a few statistical properties of the community. We give an ecological interpretation of this "disordered" limit where structure fails to emerge from complexity. We also demonstrate that some well-studied interaction patterns remain relevant in large ecosystems, but their impact can be encapsulated in a minimal number of additional parameters. Our approach provides a powerful framework for predicting the outcomes of ecosystem assembly and quantifying the added value of more detailed models and measurements.}, } @article {pmid29440486, year = {2018}, author = {Cornwallis, CK}, title = {Cooperative breeding and the evolutionary coexistence of helper and nonhelper strategies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1684-1686}, pmid = {29440486}, issn = {1091-6490}, mesh = {*Biological Evolution ; *Breeding ; Cooperative Behavior ; Reproduction ; }, } @article {pmid29440485, year = {2018}, author = {Yamagata, M and Sanes, JR}, title = {Reporter-nanobody fusions (RANbodies) as versatile, small, sensitive immunohistochemical reagents.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2126-2131}, pmid = {29440485}, issn = {1091-6490}, support = {R37 NS029169/NS/NINDS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Antibody Specificity ; Antigen-Antibody Reactions ; Camelus/immunology ; DNA, Complementary/*chemistry/metabolism ; Enzyme-Linked Immunosorbent Assay ; Green Fluorescent Proteins/metabolism ; Immunohistochemistry ; Sensitivity and Specificity ; Single-Domain Antibodies/chemistry/*physiology ; }, abstract = {Sensitive and specific antibodies are essential for detecting molecules in cells and tissues. However, currently used polyclonal and monoclonal antibodies are often less specific than desired, difficult to produce, and available in limited quantities. A promising recent approach to circumvent these limitations is to employ chemically defined antigen-combining domains called "nanobodies," derived from single-chain camelid antibodies. Here, we used nanobodies to prepare sensitive unimolecular detection reagents by genetically fusing cDNAs encoding nanobodies to enzymatic or antigenic reporters. We call these fusions between a reporter and a nanobody "RANbodies." They can be used to localize epitopes and to amplify signals from fluorescent proteins. They can be generated and purified simply and in unlimited amounts and can be preserved safely and inexpensively in the form of DNA or digital sequence.}, } @article {pmid29440484, year = {2018}, author = {Larsson, CA and Moyer, SM and Liu, B and Michel, KA and Pant, V and Yang, P and Wong, J and El-Naggar, AK and Krahe, R and Lozano, G}, title = {Synergistic and additive effect of retinoic acid in circumventing resistance to p53 restoration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2198-2203}, pmid = {29440484}, issn = {1091-6490}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R01 CA082577/CA/NCI NIH HHS/United States ; T32 CA009299/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents, Hormonal/administration & dosage/pharmacokinetics/pharmacology ; Drug Resistance, Neoplasm ; Drug Synergism ; Gene Expression Regulation, Neoplastic/*drug effects ; Mice ; Mice, Inbred Strains ; Mutation, Missense ; Neoplasms, Experimental/*drug therapy ; Retinoids/administration & dosage/pharmacokinetics/*pharmacology ; Tamoxifen/administration & dosage/pharmacokinetics/*pharmacology ; Transcriptome ; Tumor Necrosis Factor-alpha/metabolism ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {TP53 mutations occur in ∼50% of all human tumors, with increased frequency in aggressive cancers that are notoriously difficult to treat. Additionally, p53 missense mutations are remarkably predictive of refractoriness to chemo/radiotherapy in various malignancies. These observations have led to the development of mutant p53-targeting agents that restore p53 function. An important unknown is which p53-mutant tumors will respond to p53 reactivation-based therapies. Here, we found a heterogeneous impact on therapeutic response to p53 restoration, suggesting that it will unlikely be effective as a monotherapy. Through gene expression profiling of p53R172H -mutant lymphomas, we identified retinoic acid receptor gamma (RARγ) as an actionable target and demonstrated that pharmacological activation of RARγ with a synthetic retinoid sensitizes resistant p53-mutant lymphomas to p53 restoration, while additively improving outcome and survival in inherently sensitive tumors.}, } @article {pmid29440446, year = {2018}, author = {Emery, I}, title = {Without animals, US farmers would reduce feed crop production.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1703}, pmid = {29440446}, issn = {1091-6490}, mesh = {Agriculture ; Animal Feed/analysis ; Animals ; *Crop Production ; *Farmers ; }, } @article {pmid29440445, year = {2018}, author = {Springmann, M and Clark, M and Willett, W}, title = {Feedlot diet for Americans that results from a misspecified optimization algorithm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1704-E1705}, pmid = {29440445}, issn = {1091-6490}, mesh = {Algorithms ; Animal Feed/*analysis ; *Diet ; United States ; }, } @article {pmid29440444, year = {2018}, author = {Van Meerbeek, K and Svenning, JC}, title = {Causing confusion in the debate about the transition toward a more plant-based diet.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1701-E1702}, pmid = {29440444}, issn = {1091-6490}, mesh = {*Confusion ; *Diet ; Humans ; }, } @article {pmid29440443, year = {2018}, author = {White, RR and Hall, MB}, title = {Reply to Van Meerbeek and Svenning, Emery, and Springmann et al.: Clarifying assumptions and objectives in evaluating effects of food system shifts on human diets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1706-E1708}, pmid = {29440443}, issn = {1091-6490}, mesh = {*Diet ; Humans ; }, } @article {pmid29440442, year = {2018}, author = {Matyszewski, M and Morrone, SR and Sohn, J}, title = {Digital signaling network drives the assembly of the AIM2-ASC inflammasome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1963-E1972}, pmid = {29440442}, issn = {1091-6490}, mesh = {CARD Signaling Adaptor Proteins/*metabolism ; Caspase 1/metabolism ; Cytoplasm/metabolism ; Cytoskeletal Proteins/metabolism ; DNA/*genetics ; DNA-Binding Proteins/*metabolism ; Feedback, Physiological ; Fluorescence Resonance Energy Transfer ; Humans ; Immunity, Innate ; Inflammasomes/*metabolism ; Monte Carlo Method ; Nuclear Proteins/metabolism ; Signal Transduction ; }, abstract = {The AIM2-ASC inflammasome is a filamentous signaling platform essential for mounting host defense against cytoplasmic dsDNA arising not only from invading pathogens but also from damaged organelles. Currently, the design principles of its underlying signaling network remain poorly understood at the molecular level. We show here that longer dsDNA is more effective in inducing AIM2 assembly, its self-propagation, and downstream ASC polymerization. This observation is related to the increased probability of forming the base of AIM2 filaments, and indicates that the assembly discerns small dsDNA as noise at each signaling step. Filaments assembled by receptor AIM2, downstream ASC, and their joint complex all persist regardless of dsDNA, consequently generating sustained signal amplification and hysteresis. Furthermore, multiple positive feedback loops reinforce the assembly, as AIM2 and ASC filaments accelerate the assembly of nascent AIM2 with or without dsDNA. Together with a quantitative model of the assembly, our results indicate that an ultrasensitive digital circuit drives the assembly of the AIM2-ASC inflammasome.}, } @article {pmid29440441, year = {2018}, author = {Zhai, Z and Wang, Y and Jiang, H}, title = {Origami-inspired, on-demand deployable and collapsible mechanical metamaterials with tunable stiffness.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2032-2037}, pmid = {29440441}, issn = {1091-6490}, abstract = {Origami has been employed to build deployable mechanical metamaterials through folding and unfolding along the crease lines. Deployable metamaterials are usually flexible, particularly along their deploying and collapsing directions, which unfortunately in many cases leads to an unstable deployed state, i.e., small perturbations may collapse the structure along the same deployment path. Here we create an origami-inspired mechanical metamaterial with on-demand deployability and selective collapsibility through energy analysis. This metamaterial has autonomous deployability from the collapsed state and can be selectively collapsed along two different paths, embodying low stiffness for one path and substantially high stiffness for another path. The created mechanical metamaterial yields load-bearing capability in the deployed direction while possessing great deployability and collapsibility. The principle in this work can be utilized to design and create versatile origami-inspired mechanical metamaterials that can find many applications.}, } @article {pmid29440440, year = {2018}, author = {Denisko, D and Hoffman, MM}, title = {Classification and interaction in random forests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1690-1692}, pmid = {29440440}, issn = {1091-6490}, mesh = {*Algorithms ; Catheter Ablation ; Humans ; Varicose Veins/*therapy ; }, } @article {pmid29440439, year = {2018}, author = {Meng, H and Liu, Z and Li, X and Wang, H and Jin, T and Wu, G and Shan, B and Christofferson, DE and Qi, C and Yu, Q and Li, Y and Yuan, J}, title = {Death-domain dimerization-mediated activation of RIPK1 controls necroptosis and RIPK1-dependent apoptosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2001-E2009}, pmid = {29440439}, issn = {1091-6490}, support = {R01 AG047231/AG/NIA NIH HHS/United States ; R01 NS082257/NS/NINDS NIH HHS/United States ; RF1 AG055521/AG/NIA NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Animals ; *Apoptosis ; Cell Survival ; Enzyme Activation ; Exons ; Genetic Complementation Test ; HEK293 Cells ; Humans ; Inflammation/metabolism ; Mice ; Mice, Inbred C57BL ; Mutation ; Necrosis/genetics ; Phosphorylation ; Protein Binding ; Protein Domains ; Protein Multimerization ; Receptor-Interacting Protein Serine-Threonine Kinases/*chemistry ; Signal Transduction ; Tumor Necrosis Factor-alpha/*chemistry/metabolism ; }, abstract = {RIPK1 is a critical mediator of cell death and inflammation downstream of TNFR1 upon stimulation by TNFα, a potent proinflammatory cytokine involved in a multitude of human inflammatory and degenerative diseases. RIPK1 contains an N-terminal kinase domain, an intermediate domain, and a C-terminal death domain (DD). The kinase activity of RIPK1 promotes cell death and inflammation. Here, we investigated the involvement of RIPK1-DD in the regulation of RIPK1 kinase activity. We show that a charge-conserved mutation of a lysine located on the surface of DD (K599R in human RIPK1 or K584R in murine RIPK1) blocks RIPK1 activation in necroptosis and RIPK1-dependent apoptosis and the formation of complex II. Ripk1K584R/K584R knockin mutant cells are resistant to RIPK1 kinase-dependent apoptosis and necroptosis. The resistance of K584R cells, however, can be overcome by forced dimerization of RIPK1. Finally, we show that the K584R RIPK1 knockin mutation protects mice against TNFα-induced systematic inflammatory response syndrome. Our study demonstrates the role of RIPK1-DD in mediating RIPK1 dimerization and activation of its kinase activity during necroptosis and RIPK1-dependent apoptosis.}, } @article {pmid29440438, year = {2018}, author = {Pinsky, ML}, title = {Throwing back the big ones saves a fishery from hot water.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1678-1680}, pmid = {29440438}, issn = {1091-6490}, mesh = {*Fisheries ; *Sports ; Water ; }, } @article {pmid29440437, year = {2018}, author = {Yoccoz, NG and Ellingsen, KE and Tveraa, T}, title = {Biodiversity may wax or wane depending on metrics or taxa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1681-1683}, pmid = {29440437}, issn = {1091-6490}, mesh = {*Biodiversity ; *Ecosystem ; }, } @article {pmid29440436, year = {2018}, author = {Thornton, IM}, title = {Stepping into the genetics of biological motion processing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1687-1689}, pmid = {29440436}, issn = {1091-6490}, mesh = {*Locomotion ; *Motion ; }, } @article {pmid29440435, year = {2018}, author = {Lafferty, KD and Hopkins, SR}, title = {Unique parasite aDNA in moa coprolites from New Zealand suggests mass parasite extinctions followed human-induced megafauna extinctions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1411-1413}, pmid = {29440435}, issn = {1091-6490}, mesh = {Animals ; *Extinction, Biological ; Fossils ; New Zealand ; *Parasites ; Thoracica ; }, } @article {pmid29440434, year = {2018}, author = {Hoffecker, JF}, title = {The complexity of Neanderthal technology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1959-1961}, pmid = {29440434}, issn = {1091-6490}, } @article {pmid29440433, year = {2018}, author = {Finkle, JD and Wu, JJ and Bagheri, N}, title = {Windowed Granger causal inference strategy improves discovery of gene regulatory networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2252-2257}, pmid = {29440433}, issn = {1091-6490}, support = {F31 HL134331/HL/NHLBI NIH HHS/United States ; T32 GM008449/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Computational Biology ; Escherichia coli/metabolism ; *Gene Expression Profiling ; *Gene Regulatory Networks ; Protein Processing, Post-Translational ; Saccharomyces cerevisiae/metabolism ; }, abstract = {Accurate inference of regulatory networks from experimental data facilitates the rapid characterization and understanding of biological systems. High-throughput technologies can provide a wealth of time-series data to better interrogate the complex regulatory dynamics inherent to organisms, but many network inference strategies do not effectively use temporal information. We address this limitation by introducing Sliding Window Inference for Network Generation (SWING), a generalized framework that incorporates multivariate Granger causality to infer network structure from time-series data. SWING moves beyond existing Granger methods by generating windowed models that simultaneously evaluate multiple upstream regulators at several potential time delays. We demonstrate that SWING elucidates network structure with greater accuracy in both in silico and experimentally validated in vitro systems. We estimate the apparent time delays present in each system and demonstrate that SWING infers time-delayed, gene-gene interactions that are distinct from baseline methods. By providing a temporal framework to infer the underlying directed network topology, SWING generates testable hypotheses for gene-gene influences.}, } @article {pmid29440432, year = {2018}, author = {Zheng, L and Conner, SD}, title = {PI5P4Kγ functions in DTX1-mediated Notch signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1983-E1990}, pmid = {29440432}, issn = {1091-6490}, mesh = {Cell Line, Tumor ; Cell Membrane/metabolism ; Cell Survival ; Endosomes/metabolism ; Green Fluorescent Proteins/metabolism ; HeLa Cells ; Humans ; Lipids/chemistry ; Lysosomes/metabolism ; Phosphotransferases (Alcohol Group Acceptor)/genetics/*metabolism/physiology ; RNA, Small Interfering/metabolism ; Receptors, Notch/*metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases/*metabolism ; Ubiquitination ; rab4 GTP-Binding Proteins/metabolism ; }, abstract = {Notch signaling is an evolutionarily conserved pathway that is essential for development, where it controls processes ranging from cell differentiation to survival. Transport through endosomes is a critical step in regulating Notch signaling capacity, where the E3 ubiquitin ligase DTX1 is thought to control Notch1 intracellular transport decisions by direct receptor ubiquitination. However, how DTX1 regulates Notch1 transport within endosomes and the consequence of Notch1 ubiquitination by DTX1 remain unresolved. Here we demonstrate that DTX1 colocalizes with Notch1 on tubulovesicular recycling endosomes. We find that DTX1 silencing leads to enhanced Notch1 recycling from this compartment to the cell surface via a rab4a-mediated transport route. This, in turn, increases Notch1 cell-surface levels and enhances signaling. Surprisingly, we discovered that DTX1 depletion also elevates Notch1 activity mediated by a mutant form of the receptor that lacks lysine residues for ubiquitination, suggesting that DTX1 targets additional factors. Using an activity-based screen for ubiquitination targets, we identified multiple DTX1 substrates including PI5P4Kγ, a lipid kinase involved in PI(4,5)P2 production. Immunolocalization analysis reveals that PI5P4Kγ, like DTX1 and Notch1, is present on tubulovesicular recycling endosomes. However, in contrast to DTX1, Notch1 signaling is inhibited by pharmacological inactivation or siRNA depletion of PI5P4Kγ. Moreover, loss of PI5P4Kγ activity decreases Notch1 recycling rates and reduces receptor cell-surface levels. Collectively, these findings argue that PI5P4Kγ positively regulates the Notch pathway by promoting receptor recycling. Additionally, they support a model where DTX1 controls Notch1 endosomal sorting decisions by controlling PI5P4Kγ-mediated production of PI(4,5)P2.}, } @article {pmid29440431, year = {2018}, author = {Jin, L and Chortos, A and Lian, F and Pop, E and Linder, C and Bao, Z and Cai, W}, title = {Microstructural origin of resistance-strain hysteresis in carbon nanotube thin film conductors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1986-1991}, pmid = {29440431}, issn = {1091-6490}, abstract = {A basic need in stretchable electronics for wearable and biomedical technologies is conductors that maintain adequate conductivity under large deformation. This challenge can be met by a network of one-dimensional (1D) conductors, such as carbon nanotubes (CNTs) or silver nanowires, as a thin film on top of a stretchable substrate. The electrical resistance of CNT thin films exhibits a hysteretic dependence on strain under cyclic loading, although the microstructural origin of this strain dependence remains unclear. Through numerical simulations, analytic models, and experiments, we show that the hysteretic resistance evolution is governed by a microstructural parameter [Formula: see text] (the ratio of the mean projected CNT length over the film length) by showing that [Formula: see text] is hysteretic with strain and that the resistance is proportional to [Formula: see text] The findings are generally applicable to any stretchable thin film conductors consisting of 1D conductors with much lower resistance than the contact resistance in the high-density regime.}, } @article {pmid29440430, year = {2018}, author = {Ma, X and Guo, X and Richardson, HE and Xu, T and Xue, L}, title = {POSH regulates Hippo signaling through ubiquitin-mediated expanded degradation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2150-2155}, pmid = {29440430}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Carrier Proteins/genetics/*metabolism ; Cytoskeletal Proteins/genetics/*metabolism ; Dextran Sulfate ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics/*metabolism ; Gene Deletion ; Genome ; Intestines/drug effects ; Intracellular Signaling Peptides and Proteins/genetics/*metabolism ; Membrane Proteins/genetics/*metabolism ; Nerve Tissue Proteins/genetics/*metabolism ; Protein Binding ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Proteolysis ; Signal Transduction ; Stem Cells/drug effects ; Tumor Suppressor Proteins/genetics/metabolism ; Ubiquitin/*metabolism ; }, abstract = {The Hippo signaling pathway is a master regulator of organ growth, tissue homeostasis, and tumorigenesis. The activity of the Hippo pathway is controlled by various upstream components, including Expanded (Ex), but the precise molecular mechanism of how Ex is regulated remains poorly understood. Here we identify Plenty of SH3s (POSH), an E3 ubiquitin ligase, as a key component of Hippo signaling in DrosophilaPOSH overexpression synergizes with loss of Kibra to induce overgrowth and up-regulation of Hippo pathway target genes. Furthermore, knockdown of POSH impedes dextran sulfate sodium-induced Yorkie-dependent intestinal stem cell renewal, suggesting a physiological role of POSH in modulating Hippo signaling. Mechanistically, POSH binds to the C-terminal of Ex and is essential for the Crumbs-induced ubiquitination and degradation of Ex. Our findings establish POSH as a crucial regulator that integrates the signal from the cell surface to negatively regulate Ex-mediated Hippo activation in Drosophila.}, } @article {pmid29440429, year = {2018}, author = {Hämmerer, D and Callaghan, MF and Hopkins, A and Kosciessa, J and Betts, M and Cardenas-Blanco, A and Kanowski, M and Weiskopf, N and Dayan, P and Dolan, RJ and Düzel, E}, title = {Locus coeruleus integrity in old age is selectively related to memories linked with salient negative events.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2228-2233}, pmid = {29440429}, issn = {1091-6490}, mesh = {Adult ; Aged ; Aged, 80 and over ; Aging/*physiology ; Humans ; Locus Coeruleus/*physiology ; Magnetic Resonance Imaging ; *Memory ; Young Adult ; }, abstract = {The locus coeruleus (LC) is the principal origin of noradrenaline in the brain. LC integrity varies considerably across healthy older individuals, and is suggested to contribute to altered cognitive functions in aging. Here we test this hypothesis using an incidental memory task that is known to be susceptible to noradrenergic modulation. We used MRI neuromelanin (NM) imaging to assess LC structural integrity and pupillometry as a putative index of LC activation in both younger and older adults. We show that older adults with reduced structural LC integrity show poorer subsequent memory. This effect is more pronounced for emotionally negative events, in accord with a greater role for noradrenergic modulation in encoding salient or aversive events. In addition, we found that salient stimuli led to greater pupil diameters, consistent with increased LC activation during the encoding of such events. Our study presents novel evidence that a decrement in noradrenergic modulation impacts on specific components of cognition in healthy older adults. The findings provide a strong motivation for further investigation of the effects of altered LC integrity in pathological aging.}, } @article {pmid29440428, year = {2018}, author = {Galkina Cleary, E and Beierlein, JM and Khanuja, NS and McNamee, LM and Ledley, FD}, title = {Contribution of NIH funding to new drug approvals 2010-2016.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2329-2334}, pmid = {29440428}, issn = {1091-6490}, mesh = {*Drug Approval/economics/statistics & numerical data ; Drug Discovery/*economics ; Humans ; *National Institutes of Health (U.S.)/economics/statistics & numerical data ; Translational Medical Research/economics ; United States ; }, abstract = {This work examines the contribution of NIH funding to published research associated with 210 new molecular entities (NMEs) approved by the Food and Drug Administration from 2010-2016. We identified >2 million publications in PubMed related to the 210 NMEs (n = 131,092) or their 151 known biological targets (n = 1,966,281). Of these, >600,000 (29%) were associated with NIH-funded projects in RePORTER. This funding included >200,000 fiscal years of NIH project support (1985-2016) and project costs >$100 billion (2000-2016), representing ∼20% of the NIH budget over this period. NIH funding contributed to every one of the NMEs approved from 2010-2016 and was focused primarily on the drug targets rather than on the NMEs themselves. There were 84 first-in-class products approved in this interval, associated with >$64 billion of NIH-funded projects. The percentage of fiscal years of project funding identified through target searches, but not drug searches, was greater for NMEs discovered through targeted screening than through phenotypic methods (95% versus 82%). For targeted NMEs, funding related to targets preceded funding related to the NMEs, consistent with the expectation that basic research provides validated targets for targeted screening. This analysis, which captures basic research on biological targets as well as applied research on NMEs, suggests that the NIH contribution to research associated with new drug approvals is greater than previously appreciated and highlights the risk of reducing federal funding for basic biomedical research.}, } @article {pmid29440427, year = {2018}, author = {Hashimoto, K and Ochi, H and Sunamura, S and Kosaka, N and Mabuchi, Y and Fukuda, T and Yao, K and Kanda, H and Ae, K and Okawa, A and Akazawa, C and Ochiya, T and Futakuchi, M and Takeda, S and Sato, S}, title = {Cancer-secreted hsa-miR-940 induces an osteoblastic phenotype in the bone metastatic microenvironment via targeting ARHGAP1 and FAM134A.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2204-2209}, pmid = {29440427}, issn = {1091-6490}, mesh = {Adenocarcinoma/metabolism ; Animals ; Bone Neoplasms/*metabolism/secondary ; Bone Substitutes ; Breast Neoplasms/metabolism/*pathology ; Cell Line, Tumor ; Female ; GTPase-Activating Proteins/genetics/*metabolism ; Humans ; Male ; Membrane Proteins/genetics/*metabolism ; Mesenchymal Stem Cells ; Mice ; MicroRNAs/genetics/*metabolism ; Neoplasms, Experimental/metabolism ; Prostatic Neoplasms/*metabolism ; }, abstract = {Bone metastatic lesions are classified as osteoblastic or osteolytic lesions. Prostate and breast cancer patients frequently exhibit osteoblastic-type and osteolytic-type bone metastasis, respectively. In metastatic lesions, tumor cells interact with many different cell types, including osteoblasts, osteoclasts, and mesenchymal stem cells, resulting in an osteoblastic or osteolytic phenotype. However, the mechanisms responsible for the modification of bone remodeling have not been fully elucidated. MicroRNAs (miRNAs) are transferred between cells via exosomes and serve as intercellular communication tools, and numerous studies have demonstrated that cancer-secreted miRNAs are capable of modifying the tumor microenvironment. Thus, cancer-secreted miRNAs can induce an osteoblastic or osteolytic phenotype in the bone metastatic microenvironment. In this study, we performed a comprehensive expression analysis of exosomal miRNAs secreted by several human cancer cell lines and identified eight types of human miRNAs that were highly expressed in exosomes from osteoblastic phenotype-inducing prostate cancer cell lines. One of these miRNAs, hsa-miR-940, significantly promoted the osteogenic differentiation of human mesenchymal stem cells in vitro by targeting ARHGAP1 and FAM134A Interestingly, although MDA-MB-231 breast cancer cells are commonly known as an osteolytic phenotype-inducing cancer cell line, the implantation of miR-940-overexpressing MDA-MB-231 cells induced extensive osteoblastic lesions in the resulting tumors by facilitating the osteogenic differentiation of host mesenchymal cells. Our results suggest that the phenotypes of bone metastases can be induced by miRNAs secreted by cancer cells in the bone microenvironment.}, } @article {pmid29440426, year = {2018}, author = {Franz, KM and Neidermyer, WJ and Tan, YJ and Whelan, SPJ and Kagan, JC}, title = {STING-dependent translation inhibition restricts RNA virus replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2058-E2067}, pmid = {29440426}, issn = {1091-6490}, support = {P30 DK034854/DK/NIDDK NIH HHS/United States ; R01 AI093589/AI/NIAID NIH HHS/United States ; R01 AI116550/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autophagy ; Cyclic GMP/metabolism ; DNA, Mitochondrial/metabolism ; Fibroblasts/metabolism ; *Gene Expression Regulation ; Genome, Viral ; Interferons/metabolism ; Ligands ; Membrane Proteins/*metabolism ; Mice ; Mitochondria/metabolism ; Polyribosomes/metabolism ; RNA Viruses/*physiology ; RNA, Messenger/metabolism ; Signal Transduction ; Transcription, Genetic ; Vesicular stomatitis Indiana virus/physiology ; *Virus Replication ; }, abstract = {In mammalian cells, IFN responses that occur during RNA and DNA virus infections are activated by distinct signaling pathways. The RIG-I-like-receptors (RLRs) bind viral RNA and engage the adaptor MAVS (mitochondrial antiviral signaling) to promote IFN expression, whereas cGAS (cGMP-AMP synthase) binds viral DNA and activates an analogous pathway via the protein STING (stimulator of IFN genes). In this study, we confirm that STING is not necessary to induce IFN expression during RNA virus infection but also find that STING is required to restrict the replication of diverse RNA viruses. The antiviral activities of STING were not linked to its ability to regulate basal expression of IFN-stimulated genes, activate transcription, or autophagy. Using vesicular stomatitis virus as a model, we identified a requirement of STING to inhibit translation during infection and upon transfection of synthetic RLR ligands. This inhibition occurs at the level of translation initiation and restricts the production of viral and host proteins. The inability to restrict translation rendered STING-deficient cells 100 times more likely to support productive viral infections than wild-type counterparts. Genetic analysis linked RNA sensing by RLRs to STING-dependent translation inhibition, independent of MAVS. Thus, STING has dual functions in host defense, regulating protein synthesis to prevent RNA virus infection and regulating IFN expression to restrict DNA viruses.}, } @article {pmid29440425, year = {2018}, author = {Kornberg, MD and Smith, MD and Shirazi, HA and Calabresi, PA and Snyder, SH and Kim, PM}, title = {Bryostatin-1 alleviates experimental multiple sclerosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2186-2191}, pmid = {29440425}, issn = {1091-6490}, support = {R01 MH018501/MH/NIMH NIH HHS/United States ; R37 NS041435/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Antibodies ; Bryostatins/*therapeutic use ; CD4-Positive T-Lymphocytes ; Central Nervous System/immunology ; Encephalomyelitis, Autoimmune, Experimental/*drug therapy ; Female ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis ; }, abstract = {Multiple sclerosis (MS) is an inflammatory disorder targeting the central nervous system (CNS). The relapsing-remitting phase of MS is largely driven by peripheral activation of autoreactive T-helper (Th) 1 and Th17 lymphocytes. In contrast, compartmentalized inflammation within the CNS, including diffuse activation of innate myeloid cells, characterizes the progressive phase of MS, the most debilitating phase that currently lacks satisfactory treatments. Recently, bryostatin-1 (bryo-1), a naturally occurring, CNS-permeable compound with a favorable safety profile in humans, has been shown to act on antigen-presenting cells to promote differentiation of lymphocytes into Th2 cells, an action that might benefit Th1-driven inflammatory conditions such as MS. In the present study, we show that bryo-1 provides marked benefit in mice with experimental autoimmune encephalomyelitis (EAE), an experimental MS animal model. Preventive treatment with bryo-1 abolishes the onset of neurologic deficits in EAE. More strikingly, bryo-1 reverses neurologic deficits after EAE onset, even when treatment is initiated at a late stage of disease when peak adaptive immunity has subsided. Treatment with bryo-1 in vitro promotes an anti-inflammatory phenotype in antigen-presenting dendritic cells, macrophages, and to a lesser extent, lymphocytes. These findings suggest the potential for bryo-1 as a therapeutic agent in MS, particularly given its established clinical safety. Furthermore, the benefit of bryo-1, even in late treatment of EAE, combined with its targeting of innate myeloid cells suggests therapeutic potential in progressive forms of MS.}, } @article {pmid29440424, year = {2018}, author = {Tesfaw, AT and Pfaff, A and Golden Kroner, RE and Qin, S and Medeiros, R and Mascia, MB}, title = {Land-use and land-cover change shape the sustainability and impacts of protected areas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2084-2089}, pmid = {29440424}, issn = {1091-6490}, mesh = {Biodiversity ; *Conservation of Natural Resources/economics/legislation & jurisprudence/methods ; *Environment ; Forestry ; Government Agencies ; Humans ; Risk Factors ; }, abstract = {Protected areas (PAs) remain the dominant policy to protect biodiversity and ecosystem services but have been shown to have limited impact when development interests force them to locations with lower deforestation pressure. Far less known is that such interests also cause widespread tempering, reduction, or removal of protection [i.e., PA downgrading, downsizing, and degazettement (PADDD)]. We inform responses to PADDD by proposing and testing a bargaining explanation for PADDD risks and deforestation impacts. We examine recent degazettements for hydropower development and rural settlements in the state of Rondônia in the Brazilian Amazon. Results support two hypotheses: (i) ineffective PAs (i.e., those where internal deforestation was similar to nearby rates) were more likely to be degazetted and (ii) degazettement of ineffective PAs caused limited, if any, additional deforestation. We also report on cases in which ineffective portions were upgraded. Overall our results suggest that enhancing PAs' ecological impacts enhances their legal durability.}, } @article {pmid29440423, year = {2018}, author = {Montgomery, MG and Gahura, O and Leslie, AGW and Zíková, A and Walker, JE}, title = {ATP synthase from Trypanosoma brucei has an elaborated canonical F1-domain and conventional catalytic sites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2102-2107}, pmid = {29440423}, issn = {1091-6490}, support = {MC_EX_MR/M009858/1//Medical Research Council/United Kingdom ; MC_U105184325//Medical Research Council/United Kingdom ; MC_U105663150//Medical Research Council/United Kingdom ; }, mesh = {Catalytic Domain ; Gene Expression Regulation, Enzymologic ; Mitochondrial Proton-Translocating ATPases/genetics/*metabolism ; Models, Molecular ; Protein Conformation ; Protein Subunits ; Protozoan Proteins/genetics/*metabolism ; Trypanosoma brucei brucei/*enzymology/genetics ; }, abstract = {The structures and functions of the components of ATP synthases, especially those subunits involved directly in the catalytic formation of ATP, are widely conserved in metazoans, fungi, eubacteria, and plant chloroplasts. On the basis of a map at 32.5-Å resolution determined in situ in the mitochondria of Trypanosoma brucei by electron cryotomography, it has been proposed that the ATP synthase in this species has a noncanonical structure and different catalytic sites in which the catalytically essential arginine finger is provided not by the α-subunit adjacent to the catalytic nucleotide-binding site as in all species investigated to date, but rather by a protein, p18, found only in the euglenozoa. A crystal structure at 3.2-Å resolution of the catalytic domain of the same enzyme demonstrates that this proposal is incorrect. In many respects, the structure is similar to the structures of F1-ATPases determined previously. The α3β3-spherical portion of the catalytic domain in which the three catalytic sites are found, plus the central stalk, are highly conserved, and the arginine finger is provided conventionally by the α-subunits adjacent to each of the three catalytic sites found in the β-subunits. Thus, the enzyme has a conventional catalytic mechanism. The structure differs from previous described structures by the presence of a p18 subunit, identified only in the euglenozoa, associated with the external surface of each of the three α-subunits, thereby elaborating the F1-domain. Subunit p18 is a pentatricopeptide repeat (PPR) protein with three PPRs and appears to have no function in the catalytic mechanism of the enzyme.}, } @article {pmid29440422, year = {2018}, author = {Gay-Antaki, M and Liverman, D}, title = {Climate for women in climate science: Women scientists and the Intergovernmental Panel on Climate Change.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2060-2065}, pmid = {29440422}, issn = {1091-6490}, mesh = {*Climate Change ; Communication ; Data Collection ; Female ; Government ; Humans ; Interinstitutional Relations ; Research/*statistics & numerical data ; *Women ; Women's Rights ; }, abstract = {The Intergovernmental Panel on Climate Change (IPCC) is an authoritative and influential source of reports on climate change. The lead authors of IPCC reports include scientists from around the world, but questions have been raised about the dominance of specific disciplines in the report and the disproportionate number of scholars from the Global North. In this paper, we analyze the as-yet-unexamined issue of gender and IPCC authorship, looking at changes in gender balance over time and analyzing women's views about their experience and barriers to full participation, not only as women but also at the intersection of nationality, race, command of English, and discipline. Over time, we show that the proportion of female IPCC authors has seen a modest increase from less than 5% in 1990 to more than 20% in the most recent assessment reports. Based on responses from over 100 women IPCC authors, we find that many women report a positive experience in the way in which they are treated and in their ability to influence the report, although others report that some women were poorly represented and heard. We suggest that an intersectional lens is important: not all women experience the same obstacles: they face multiple and diverse barriers associated with social identifiers such as race, nationality, command of English, and disciplinary affiliation. The scientific community benefits from including all scientists, including women and those from the Global South. This paper documents barriers to participation and identifies opportunities to diversify climate science.}, } @article {pmid29440421, year = {2018}, author = {Allaire, M and Wu, H and Lall, U}, title = {National trends in drinking water quality violations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2078-2083}, pmid = {29440421}, issn = {1091-6490}, mesh = {Drinking Water ; Humans ; Safety ; United States ; Water Pollutants/*standards ; Water Quality/*standards ; Water Supply/*legislation & jurisprudence/*standards ; }, abstract = {Ensuring safe water supply for communities across the United States is a growing challenge in the face of aging infrastructure, impaired source water, and strained community finances. In the aftermath of the Flint lead crisis, there is an urgent need to assess the current state of US drinking water. However, no nationwide assessment has yet been conducted on trends in drinking water quality violations across several decades. Efforts to reduce violations are of national concern given that, in 2015, nearly 21 million people relied on community water systems that violated health-based quality standards. In this paper, we evaluate spatial and temporal patterns in health-related violations of the Safe Drinking Water Act using a panel dataset of 17,900 community water systems over the period 1982-2015. We also identify vulnerability factors of communities and water systems through probit regression. Increasing time trends and violation hot spots are detected in several states, particularly in the Southwest region. Repeat violations are prevalent in locations of violation hot spots, indicating that water systems in these regions struggle with recurring issues. In terms of vulnerability factors, we find that violation incidence in rural areas is substantially higher than in urbanized areas. Meanwhile, private ownership and purchased water source are associated with compliance. These findings indicate the types of underperforming systems that might benefit from assistance in achieving consistent compliance. We discuss why certain violations might be clustered in some regions and strategies for improving national drinking water quality.}, } @article {pmid29440420, year = {2018}, author = {Thorlakson, T and de Zegher, JF and Lambin, EF}, title = {Companies' contribution to sustainability through global supply chains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2072-2077}, pmid = {29440420}, issn = {1091-6490}, abstract = {Global supply chains play a critical role in many of the most pressing environmental stresses and social struggles identified by the United Nations' Sustainable Development Goals (SDGs). Responding to calls from the global community, companies are adopting a variety of voluntary practices to improve the environmental and/or social management of their suppliers' activities. We develop a global survey of 449 publicly listed companies in the food, textile, and wood-products sectors with annual reports in English to provide insight into how the private sector contributes to advancing the SDGs via such sustainable-sourcing practices. We find that while 52% of companies use at least one sustainable-sourcing practice, these practices are limited in scope; 71% relates to only one or a few input materials and 60.5% apply to only first-tier suppliers. We also find that sustainable-sourcing practices typically address a small subset of the sustainability challenges laid out by the SDGs, primarily focusing on labor rights and compliance with national laws. Consistent with existing hypotheses, companies that face consumer and civil society pressure are associated with a significantly higher probability of adopting sustainable-sourcing practices. Our findings highlight the opportunities and limitations of corporate sustainable-sourcing practices in addressing the myriad sustainability challenges facing our world today.}, } @article {pmid29440419, year = {2018}, author = {Ji, Y and Liu, P and Yuen, T and Haider, S and He, J and Romero, R and Chen, H and Bloch, M and Kim, SM and Lizneva, D and Munshi, L and Zhou, C and Lu, P and Iqbal, J and Cheng, Z and New, MI and Hsueh, AJ and Bian, Z and Rosen, CJ and Sun, L and Zaidi, M}, title = {Epitope-specific monoclonal antibodies to FSHβ increase bone mass.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2192-2197}, pmid = {29440419}, issn = {1091-6490}, support = {R01 AR067066/AR/NIAMS NIH HHS/United States ; P30 GM106391/GM/NIGMS NIH HHS/United States ; R24 DK092759/DK/NIDDK NIH HHS/United States ; R01 AG040132/AG/NIA NIH HHS/United States ; R01 AR065932/AR/NIAMS NIH HHS/United States ; U54 GM115516/GM/NIGMS NIH HHS/United States ; P20 GM103465/GM/NIGMS NIH HHS/United States ; R01 DK080459/DK/NIDDK NIH HHS/United States ; R01 DK113627/DK/NIDDK NIH HHS/United States ; R01 AG023176/AG/NIA NIH HHS/United States ; P30 GM103392/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/*pharmacology ; Antibody Specificity ; Bone Density ; Bone Resorption ; Catalytic Domain ; *Epitopes ; Female ; Follicle Stimulating Hormone, beta Subunit/*immunology ; Gene Expression Regulation/drug effects/immunology ; Humans ; Mice ; Mice, Inbred BALB C ; Models, Molecular ; Ovariectomy ; Protein Binding ; Protein Conformation ; }, abstract = {Pituitary hormones have long been thought solely to regulate single targets. Challenging this paradigm, we discovered that both anterior and posterior pituitary hormones, including FSH, had other functions in physiology. We have shown that FSH regulates skeletal integrity, and, more recently, find that FSH inhibition reduces body fat and induces thermogenic adipose tissue. A polyclonal antibody raised against a short, receptor-binding epitope of FSHβ was found not only to rescue bone loss postovariectomy, but also to display marked antiobesity and probeiging actions. Questioning whether a single agent could be used to treat two medical conditions of public health importance--osteoporosis and obesity--we developed two further monoclonal antibodies, Hf2 and Mf4, against computationally defined receptor-binding epitopes of FSHβ. Hf2 has already been shown to reduce body weight and fat mass and cause beiging in mice on a high-fat diet. Here, we show that Hf2, which binds mouse Fsh in immunoprecipitation assays, also increases cortical thickness and trabecular bone volume, and microstructural parameters, in sham-operated and ovariectomized mice, noted on microcomputed tomography. This effect was largely recapitulated with Mf4, which inhibited bone resorption by osteoclasts and stimulated new bone formation by osteoblasts. These effects were exerted in the absence of alterations in serum estrogen in wild-type mice. We also reconfirm the existence of Fshrs in bone by documenting the specific binding of fluorescently labeled FSH, FSH-CH, in vivo. Our study provides the framework for the future development of an FSH-based therapeutic that could potentially target both bone and fat.}, } @article {pmid29440418, year = {2018}, author = {Purohit, R and Ross, MO and Batelu, S and Kusowski, A and Stemmler, TL and Hoffman, BM and Rosenzweig, AC}, title = {Cu+-specific CopB transporter: Revising P1B-type ATPase classification.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2108-2113}, pmid = {29440418}, issn = {1091-6490}, support = {R35 GM118035/GM/NIGMS NIH HHS/United States ; R01 GM058518/GM/NIGMS NIH HHS/United States ; R01 GM111097/GM/NIGMS NIH HHS/United States ; R01 DK068139/DK/NIDDK NIH HHS/United States ; T32 GM008382/GM/NIGMS NIH HHS/United States ; P41 GM103393/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/*classification/genetics/*metabolism ; Binding Sites ; Biological Transport ; Cation Transport Proteins/*classification/genetics/*metabolism ; Copper/*metabolism ; Gene Expression Regulation, Enzymologic/*physiology ; Genetic Variation ; Protein Binding ; Sequence Alignment ; Sulfur ; }, abstract = {The copper-transporting P1B-ATPases, which play a key role in cellular copper homeostasis, have been divided traditionally into two subfamilies, the P1B-1-ATPases or CopAs and the P1B-3-ATPases or CopBs. CopAs selectively export Cu+ whereas previous studies and bioinformatic analyses have suggested that CopBs are specific for Cu2+ export. Biochemical and spectroscopic characterization of Sphaerobacter thermophilus CopB (StCopB) show that, while it does bind Cu2+, the binding site is not the prototypical P1B-ATPase transmembrane site and does not involve sulfur coordination as proposed previously. Most important, StCopB exhibits metal-stimulated ATPase activity in response to Cu+, but not Cu2+, indicating that it is actually a Cu+ transporter. X-ray absorption spectroscopic studies indicate that Cu+ is coordinated by four sulfur ligands, likely derived from conserved cysteine and methionine residues. The histidine-rich N-terminal region of StCopB is required for maximal activity, but is inhibitory in the presence of divalent metal ions. Finally, reconsideration of the P1B-ATPase classification scheme suggests that the P1B-1- and P1B-3-ATPase subfamilies both comprise Cu+ transporters. These results are completely consistent with the known presence of only Cu+ within the reducing environment of the cytoplasm, which should eliminate the need for a Cu2+ P1B-ATPase.}, } @article {pmid29440417, year = {2018}, author = {Kawano, M and Nagata, S}, title = {Lupus-like autoimmune disease caused by a lack of Xkr8, a caspase-dependent phospholipid scramblase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2132-2137}, pmid = {29440417}, issn = {1091-6490}, mesh = {Animals ; Apoptosis ; Apoptosis Regulatory Proteins/genetics/*metabolism ; Autoantibodies/*metabolism ; Autoimmune Diseases/*etiology/metabolism ; Cells, Cultured ; Gene Expression Regulation, Enzymologic/*physiology ; Lymphocytes/physiology ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neutrophils/physiology ; Phagocytes/physiology ; Phosphatidylserines/metabolism ; Spleen/enzymology ; Thymocytes/enzymology/metabolism ; }, abstract = {Apoptotic cells expose phosphatidylserine (PtdSer) on their cell surface and are recognized by macrophages for clearance. Xkr8 is a scramblase that exposes PtdSer in a caspase-dependent manner. Here, we found that among the three Xkr members with caspase-dependent scramblase activity, mouse hematopoietic cells express only Xkr8. The PtdSer exposure of apoptotic thymocytes, splenocytes, and neutrophils was strongly reduced when Xkr8 was absent. While wild-type apoptotic lymphocytes and neutrophils were efficiently engulfed in vitro by phagocytes expressing Tim4 and MerTK, Xkr8-deficient apoptotic cells were hardly engulfed by these phagocytes. Accordingly, the number of apoptotic thymocytes in the thymus and neutrophils in the peritoneal cavity of the zymosan-treated mice was significantly increased in Xkr8-deficient mice. The percentage of CD62Llo senescent neutrophils was increased in the spleen of Xkr8-null mice, especially after the treatment with granulocyte colony-stimulating factor. Xkr8-null mice on an MRL background showed high levels of autoantibodies, splenomegaly with high levels of effector CD4 T cells, and glomerulonephritis development with immune-complex deposition at glomeruli. These results indicate that the Xkr8-mediated PtdSer exposure in apoptotic lymphocytes and aged neutrophils is essential for their clearance, and its defect activates the immune system, leading to lupus-like autoimmune disease.}, } @article {pmid29440416, year = {2018}, author = {Magurran, AE and Deacon, AE and Moyes, F and Shimadzu, H and Dornelas, M and Phillip, DAT and Ramnarine, IW}, title = {Divergent biodiversity change within ecosystems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1843-1847}, pmid = {29440416}, issn = {1091-6490}, support = {250189//European Research Council/International ; }, mesh = {Animals ; *Biodiversity ; Computer Simulation ; Fishes/classification ; Fresh Water ; Invertebrates/classification ; *Models, Biological ; Plants/classification ; Population Dynamics ; }, abstract = {The Earth's ecosystems are under unprecedented pressure, yet the nature of contemporary biodiversity change is not well understood. Growing evidence that community size is regulated highlights the need for improved understanding of community dynamics. As stability in community size could be underpinned by marked temporal turnover, a key question is the extent to which changes in both biodiversity dimensions (temporal α- and temporal β-diversity) covary within and among the assemblages that comprise natural communities. Here, we draw on a multiassemblage dataset (encompassing vertebrates, invertebrates, and unicellular plants) from a tropical freshwater ecosystem and employ a cyclic shift randomization to assess whether any directional change in temporal α-diversity and temporal β-diversity exceeds baseline levels. In the majority of cases, α-diversity remains stable over the 5-y time frame of our analysis, with little evidence for systematic change at the community level. In contrast, temporal β-diversity changes are more prevalent, and the two diversity dimensions are decoupled at both the within- and among-assemblage level. Consequently, a pressing research challenge is to establish how turnover supports regulation and when elevated temporal β-diversity jeopardizes community integrity.}, } @article {pmid29440415, year = {2018}, author = {Boast, AP and Weyrich, LS and Wood, JR and Metcalf, JL and Knight, R and Cooper, A}, title = {Coprolites reveal ecological interactions lost with the extinction of New Zealand birds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1546-1551}, pmid = {29440415}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/*physiology ; Birds/*physiology ; DNA/*analysis/genetics ; *Ecology ; *Extinction, Biological ; *Fossils ; Fungi/genetics ; Palaeognathae/*physiology ; Parasites/genetics ; Plants/genetics ; }, abstract = {Over the past 50,000 y, biotic extinctions and declines have left a legacy of vacant niches and broken ecological interactions across global terrestrial ecosystems. Reconstructing the natural, unmodified ecosystems that preceded these events relies on high-resolution analyses of paleoecological deposits. Coprolites are a source of uniquely detailed information about trophic interactions and the behaviors, gut parasite communities, and microbiotas of prehistoric animal species. Such insights are critical for understanding the legacy effects of extinctions on ecosystems, and can help guide contemporary conservation and ecosystem restoration efforts. Here we use high-throughput sequencing (HTS) of ancient eukaryotic DNA from coprolites to reconstruct aspects of the biology and ecology of four species of extinct moa and the critically endangered kakapo parrot from New Zealand (NZ). Importantly, we provide evidence that moa and prehistoric kakapo consumed ectomycorrhizal fungi, suggesting these birds played a role in dispersing fungi that are key to NZ's natural forest ecosystems. We also provide the first DNA-based evidence that moa frequently supplemented their broad diets with ferns and mosses. Finally, we also find parasite taxa that provide insight into moa behavior, and present data supporting the hypothesis of coextinction between moa and several parasite species. Our study demonstrates that HTS sequencing of coprolites provides a powerful tool for resolving key aspects of ancient ecosystems and may rapidly provide information not obtainable by conventional paleoecological techniques, such as fossil analyses.}, } @article {pmid29440414, year = {2018}, author = {Day, JA and Fung, I and Liu, W}, title = {Changing character of rainfall in eastern China, 1951-2007.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2016-2021}, pmid = {29440414}, issn = {1091-6490}, abstract = {The topography and continental configuration of East Asia favor the year-round existence of storm tracks that extend thousands of kilometers from China into the northwestern Pacific Ocean, producing zonally elongated patterns of rainfall that we call "frontal rain events." In spring and early summer (known as "Meiyu Season"), frontal rainfall intensifies and shifts northward during a series of stages collectively known as the East Asian summer monsoon. Using a technique called the Frontal Rain Event Detection Algorithm, we create a daily catalog of all frontal rain events in east China during 1951-2007, quantify their attributes, and classify all rainfall on each day as either frontal, resulting from large-scale convergence, or nonfrontal, produced by local buoyancy, topography, or typhoons. Our climatology shows that the East Asian summer monsoon consists of a series of coupled changes in frontal rain event frequency, latitude, and daily accumulation. Furthermore, decadal changes in the amount and distribution of rainfall in east China are overwhelmingly due to changes in frontal rainfall. We attribute the "South Flood-North Drought" pattern observed beginning in the 1980s to changes in the frequency of frontal rain events, while the years 1994-2007 witnessed an uptick in event daily accumulation relative to the rest of the study years. This particular signature may reflect the relative impacts of global warming, aerosol loading, and natural variability on regional rainfall, potentially via shifting the East Asian jet stream.}, } @article {pmid29440413, year = {2018}, author = {Giardino Torchia, ML and Dutta, D and Mittelstadt, PR and Guha, J and Gaida, MM and Fish, K and Barr, VA and Akpan, IO and Samelson, LE and Tagad, HD and Debnath, S and Miller Jenkins, LM and Appella, E and Ashwell, JD}, title = {Intensity and duration of TCR signaling is limited by p38 phosphorylation of ZAP-70T293 and destabilization of the signalosome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2174-2179}, pmid = {29440413}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Gene Expression Regulation ; Genes, T-Cell Receptor/*physiology ; Humans ; Jurkat Cells ; Phosphorylation ; Signal Transduction ; ZAP-70 Protein-Tyrosine Kinase/genetics/*metabolism ; p38 Mitogen-Activated Protein Kinases/genetics/*metabolism ; }, abstract = {ZAP-70 is a tyrosine kinase that is essential for initiation of T cell antigen receptor (TCR) signaling. We have found that T cell p38 MAP kinase (MAPK), which is directly phosphorylated and activated by ZAP-70 downstream of the TCR, in turn phosphorylates Thr-293 in the interdomain B region of ZAP-70. Mutant T cells expressing ZAP-70 with an alanine substitution at this residue (ZAP-70T293A) had enhanced TCR proximal signaling and increased effector responses. Lack of ZAP-70T293 phosphorylation increased association of ZAP-70 with the TCR and prolonged the existence of TCR signaling microclusters. These results identify a tight negative feedback loop in which ZAP-70-activated p38 reciprocally phosphorylates ZAP-70 and destabilizes the signaling complex.}, } @article {pmid29440412, year = {2018}, author = {Ducati, RG and Namanja-Magliano, HA and Harijan, RK and Fajardo, JE and Fiser, A and Daily, JP and Schramm, VL}, title = {Genetic resistance to purine nucleoside phosphorylase inhibition in Plasmodium falciparum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2114-2119}, pmid = {29440412}, issn = {1091-6490}, support = {R01 AI049512/AI/NIAID NIH HHS/United States ; R37 GM041916/GM/NIGMS NIH HHS/United States ; R01 GM041916/GM/NIGMS NIH HHS/United States ; T32 AI070117/AI/NIAID NIH HHS/United States ; U19 AI089683/AI/NIAID NIH HHS/United States ; }, mesh = {Adenosine/*analogs & derivatives/pharmacology ; Antimalarials/*pharmacology ; Drug Resistance ; Enzyme Inhibitors/*pharmacology ; Genomics ; Models, Molecular ; Plasmodium falciparum/drug effects/*enzymology/genetics ; Point Mutation ; Protein Conformation ; Purine-Nucleoside Phosphorylase/*antagonists & inhibitors ; Pyrrolidines/*pharmacology ; }, abstract = {Plasmodium falciparum causes the most lethal form of human malaria and is a global health concern. The parasite responds to antimalarial therapies by developing drug resistance. The continuous development of new antimalarials with novel mechanisms of action is a priority for drug combination therapies. The use of transition-state analog inhibitors to block essential steps in purine salvage has been proposed as a new antimalarial approach. Mutations that reduce transition-state analog binding are also expected to reduce the essential catalytic function of the target. We have previously reported that inhibition of host and P. falciparum purine nucleoside phosphorylase (PfPNP) by DADMe-Immucillin-G (DADMe-ImmG) causes purine starvation and parasite death in vitro and in primate infection models. P. falciparum cultured under incremental DADMe-ImmG drug pressure initially exhibited increased PfPNP gene copy number and protein expression. At increased drug pressure, additional PfPNP gene copies appeared with point mutations at catalytic site residues involved in drug binding. Mutant PfPNPs from resistant clones demonstrated reduced affinity for DADMe-ImmG, but also reduced catalytic efficiency. The catalytic defects were partially overcome by gene amplification in the region expressing PfPNP. Crystal structures of native and mutated PfPNPs demonstrate altered catalytic site contacts to DADMe-ImmG. Both point mutations and gene amplification are required to overcome purine starvation induced by DADMe-ImmG. Resistance developed slowly, over 136 generations (2136 clonal selection). Transition-state analog inhibitors against PfPNP are slow to induce resistance and may have promise in malaria therapy.}, } @article {pmid29440411, year = {2018}, author = {Lin, C and Smith, JS and Sinogeikin, SV and Shen, G}, title = {Experimental evidence of low-density liquid water upon rapid decompression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2010-2015}, pmid = {29440411}, issn = {1091-6490}, abstract = {Water is an extraordinary liquid, having a number of anomalous properties which become strongly enhanced in the supercooled region. Due to rapid crystallization of supercooled water, there exists a region that has been experimentally inaccessible for studying deeply supercooled bulk water. Using a rapid decompression technique integrated with in situ X-ray diffraction, we show that a high-pressure ice phase transforms to a low-density noncrystalline (LDN) form upon rapid release of pressure at temperatures of 140-165 K. The LDN subsequently crystallizes into ice-Ic through a diffusion-controlled process. Together with the change in crystallization rate with temperature, the experimental evidence indicates that the LDN is a low-density liquid (LDL). The measured X-ray diffraction data show that the LDL is tetrahedrally coordinated with the tetrahedral network fully developed and clearly linked to low-density amorphous ices. On the other hand, there is a distinct difference in structure between the LDL and supercooled water or liquid water in terms of the tetrahedral order parameter.}, } @article {pmid29440410, year = {2018}, author = {Power, JD and Plitt, M and Gotts, SJ and Kundu, P and Voon, V and Bandettini, PA and Martin, A}, title = {Ridding fMRI data of motion-related influences: Removal of signals with distinct spatial and physical bases in multiecho data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2105-E2114}, pmid = {29440410}, issn = {1091-6490}, support = {ZIA MH002920/MH/NIMH NIH HHS/United States ; }, mesh = {Artifacts ; Brain/physiology ; Brain Mapping/*methods ; Cohort Studies ; Humans ; Image Processing, Computer-Assisted/*methods ; *Magnetic Resonance Imaging ; *Motion ; *Respiration ; Subtraction Technique ; }, abstract = {"Functional connectivity" techniques are commonplace tools for studying brain organization. A critical element of these analyses is to distinguish variance due to neurobiological signals from variance due to nonneurobiological signals. Multiecho fMRI techniques are a promising means for making such distinctions based on signal decay properties. Here, we report that multiecho fMRI techniques enable excellent removal of certain kinds of artifactual variance, namely, spatially focal artifacts due to motion. By removing these artifacts, multiecho techniques reveal frequent, large-amplitude blood oxygen level-dependent (BOLD) signal changes present across all gray matter that are also linked to motion. These whole-brain BOLD signals could reflect widespread neural processes or other processes, such as alterations in blood partial pressure of carbon dioxide (pCO2) due to ventilation changes. By acquiring multiecho data while monitoring breathing, we demonstrate that whole-brain BOLD signals in the resting state are often caused by changes in breathing that co-occur with head motion. These widespread respiratory fMRI signals cannot be isolated from neurobiological signals by multiecho techniques because they occur via the same BOLD mechanism. Respiratory signals must therefore be removed by some other technique to isolate neurobiological covariance in fMRI time series. Several methods for removing global artifacts are demonstrated and compared, and were found to yield fMRI time series essentially free of motion-related influences. These results identify two kinds of motion-associated fMRI variance, with different physical mechanisms and spatial profiles, each of which strongly and differentially influences functional connectivity patterns. Distance-dependent patterns in covariance are nearly entirely attributable to non-BOLD artifacts.}, } @article {pmid29440409, year = {2018}, author = {Zhang, H and Yee, LD and Lee, BH and Curtis, MP and Worton, DR and Isaacman-VanWertz, G and Offenberg, JH and Lewandowski, M and Kleindienst, TE and Beaver, MR and Holder, AL and Lonneman, WA and Docherty, KS and Jaoui, M and Pye, HOT and Hu, W and Day, DA and Campuzano-Jost, P and Jimenez, JL and Guo, H and Weber, RJ and de Gouw, J and Koss, AR and Edgerton, ES and Brune, W and Mohr, C and Lopez-Hilfiker, FD and Lutz, A and Kreisberg, NM and Spielman, SR and Hering, SV and Wilson, KR and Thornton, JA and Goldstein, AH}, title = {Monoterpenes are the largest source of summertime organic aerosol in the southeastern United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2038-2043}, pmid = {29440409}, issn = {1091-6490}, mesh = {Aerosols/*chemistry ; Air Pollutants/*chemistry ; Monoterpenes/*chemistry ; *Seasons ; Southeastern United States ; Time Factors ; }, abstract = {The chemical complexity of atmospheric organic aerosol (OA) has caused substantial uncertainties in understanding its origins and environmental impacts. Here, we provide constraints on OA origins through compositional characterization with molecular-level details. Our results suggest that secondary OA (SOA) from monoterpene oxidation accounts for approximately half of summertime fine OA in Centreville, AL, a forested area in the southeastern United States influenced by anthropogenic pollution. We find that different chemical processes involving nitrogen oxides, during days and nights, play a central role in determining the mass of monoterpene SOA produced. These findings elucidate the strong anthropogenic-biogenic interaction affecting ambient aerosol in the southeastern United States and point out the importance of reducing anthropogenic emissions, especially under a changing climate, where biogenic emissions will likely keep increasing.}, } @article {pmid29440408, year = {2018}, author = {Younis, S and Schönke, M and Massart, J and Hjortebjerg, R and Sundström, E and Gustafson, U and Björnholm, M and Krook, A and Frystyk, J and Zierath, JR and Andersson, L}, title = {The ZBED6-IGF2 axis has a major effect on growth of skeletal muscle and internal organs in placental mammals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2048-E2057}, pmid = {29440408}, issn = {1091-6490}, mesh = {Alleles ; Animals ; Binding Sites ; Conserved Sequence ; CpG Islands ; DNA Transposable Elements ; Female ; Insulin-Like Growth Factor II/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Muscle, Skeletal/*growth & development ; Phenotype ; Promoter Regions, Genetic ; Repressor Proteins/*genetics/*physiology ; Sequence Analysis, RNA ; Transcriptome ; Up-Regulation ; }, abstract = {A single nucleotide substitution in the third intron of insulin-like growth factor 2 (IGF2) is associated with increased muscle mass and reduced subcutaneous fat in domestic pigs. This mutation disrupts the binding of the ZBED6 transcription factor and leads to a threefold up-regulation of IGF2 expression in pig skeletal muscle. Here, we investigated the biological significance of ZBED6-IGF2 interaction in the growth of placental mammals using two mouse models, ZBED6 knock-out (Zbed6-/-) and Igf2 knock-in mice that carry the pig IGF2 mutation. These transgenic mice exhibit markedly higher serum IGF2 concentrations, higher growth rate, increased lean mass, and larger heart, kidney, and liver; no significant changes were observed for white adipose tissues. The changes in body and lean mass were most pronounced in female mice. The phenotypic changes were concomitant with a remarkable up-regulation of Igf2 expression in adult tissues. Transcriptome analysis of skeletal muscle identified differential expression of genes belonging to the extracellular region category. Expression analysis using fetal muscles indicated a minor role of ZBED6 in regulating Igf2 expression prenatally. Furthermore, transcriptome analysis of the adult skeletal muscle revealed that this elevated expression of Igf2 was derived from the P1 and P2 promoters. The results revealed very similar phenotypic effects in the Zbed6 knock-out mouse and in the Igf2 knock-in mouse, showing that the effect of ZBED6 on growth of muscle and internal organs is mediated through the binding site in the Igf2 gene. The results explain why this ZBED6 binding site is extremely well conserved among placental mammals.}, } @article {pmid29440407, year = {2018}, author = {Shaffer, G and Lambert, F}, title = {In and out of glacial extremes by way of dust-climate feedbacks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2026-2031}, pmid = {29440407}, issn = {1091-6490}, abstract = {Mineral dust aerosols cool Earth directly by scattering incoming solar radiation and indirectly by affecting clouds and biogeochemical cycles. Recent Earth history has featured quasi-100,000-y, glacial-interglacial climate cycles with lower/higher temperatures and greenhouse gas concentrations during glacials/interglacials. Global average, glacial maxima dust levels were more than 3 times higher than during interglacials, thereby contributing to glacial cooling. However, the timing, strength, and overall role of dust-climate feedbacks over these cycles remain unclear. Here we use dust deposition data and temperature reconstructions from ice sheet, ocean sediment, and land archives to construct dust-climate relationships. Although absolute dust deposition rates vary greatly among these archives, they all exhibit striking, nonlinear increases toward coldest glacial conditions. From these relationships and reconstructed temperature time series, we diagnose glacial-interglacial time series of dust radiative forcing and iron fertilization of ocean biota, and use these time series to force Earth system model simulations. The results of these simulations show that dust-climate feedbacks, perhaps set off by orbital forcing, push the system in and out of extreme cold conditions such as glacial maxima. Without these dust effects, glacial temperature and atmospheric CO2 concentrations would have been much more stable at higher, intermediate glacial levels. The structure of residual anomalies over the glacial-interglacial climate cycles after subtraction of dust effects provides constraints for the strength and timing of other processes governing these cycles.}, } @article {pmid29440406, year = {2018}, author = {Davenport, AJ and Cross, RS and Watson, KA and Liao, Y and Shi, W and Prince, HM and Beavis, PA and Trapani, JA and Kershaw, MH and Ritchie, DS and Darcy, PK and Neeson, PJ and Jenkins, MR}, title = {Chimeric antigen receptor T cells form nonclassical and potent immune synapses driving rapid cytotoxicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2068-E2076}, pmid = {29440406}, issn = {1091-6490}, mesh = {Animals ; CD3 Complex ; Cell Adhesion ; Cell Death ; Cell Line, Tumor ; Computational Biology ; Cytokines/metabolism ; Dyneins/chemistry ; Immunological Synapses/*immunology ; Ligands ; Lymphocyte Activation ; Lymphocyte Function-Associated Antigen-1/immunology ; Mice ; Microtubules/metabolism ; Neoplasms/*immunology ; Receptors, Antigen, T-Cell/*immunology ; Signal Transduction ; T-Lymphocytes, Cytotoxic/*immunology ; }, abstract = {Chimeric antigen receptor T (CAR-T) cells are effective serial killers with a faster off-rate from dying tumor cells than CAR-T cells binding target cells through their T cell receptor (TCR). Here we explored the functional consequences of CAR-mediated signaling using a dual-specific CAR-T cell, where the same cell was triggered via TCR (tcrCTL) or CAR (carCTL). The carCTL immune synapse lacked distinct LFA-1 adhesion rings and was less reliant on LFA to form stable conjugates with target cells. carCTL receptors associated with the synapse were found to be disrupted and formed a convoluted multifocal pattern of Lck microclusters. Both proximal and distal receptor signaling pathways were induced more rapidly and subsequently decreased more rapidly in carCTL than in tcrCTL. The functional consequence of this rapid signaling in carCTL cells included faster lytic granule recruitment to the immune synapse, correlating with faster detachment of the CTL from the target cell. This study provides a mechanism for how CAR-T cells can debulk large tumor burden quickly and may contribute to further refinement of CAR design for enhancing the quality of signaling and programming of the T cell.}, } @article {pmid29440405, year = {2018}, author = {}, title = {Correction for Mano et al., Optimal run-and-tumble-based transportation of a Janus particle with active steering.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1936}, doi = {10.1073/pnas.1801089115}, pmid = {29440405}, issn = {1091-6490}, } @article {pmid29440404, year = {2018}, author = {Reggente, N and Moody, TD and Morfini, F and Sheen, C and Rissman, J and O'Neill, J and Feusner, JD}, title = {Multivariate resting-state functional connectivity predicts response to cognitive behavioral therapy in obsessive-compulsive disorder.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2222-2227}, pmid = {29440404}, issn = {1091-6490}, support = {R01 MH085900/MH/NIMH NIH HHS/United States ; R21 MH110865/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Brain Mapping ; *Cognitive Behavioral Therapy ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Multivariate Analysis ; Neural Pathways ; Obsessive-Compulsive Disorder/*psychology/*therapy ; Pattern Recognition, Physiological ; Treatment Outcome ; Young Adult ; }, abstract = {Cognitive behavioral therapy (CBT) is an effective treatment for many with obsessive-compulsive disorder (OCD). However, response varies considerably among individuals. Attaining a means to predict an individual's potential response would permit clinicians to more prudently allocate resources for this often stressful and time-consuming treatment. We collected resting-state functional magnetic resonance imaging from adults with OCD before and after 4 weeks of intensive daily CBT. We leveraged machine learning with cross-validation to assess the power of functional connectivity (FC) patterns to predict individual posttreatment OCD symptom severity. Pretreatment FC patterns within the default mode network and visual network significantly predicted posttreatment OCD severity, explaining up to 67% of the variance. These networks were stronger predictors than pretreatment clinical scores. Results have clinical implications for developing personalized medicine approaches to identifying individual OCD patients who will maximally benefit from intensive CBT.}, } @article {pmid29440403, year = {2018}, author = {Gaspari, S and Purushothaman, I and Cogliani, V and Sakloth, F and Neve, RL and Howland, D and Ring, RH and Ross, EM and Shen, L and Zachariou, V}, title = {Suppression of RGSz1 function optimizes the actions of opioid analgesics by mechanisms that involve the Wnt/β-catenin pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2085-E2094}, pmid = {29440403}, issn = {1091-6490}, support = {P01 DA008227/DA/NIDA NIH HHS/United States ; R21 NS098264/NS/NINDS NIH HHS/United States ; R01 NS086444/NS/NINDS NIH HHS/United States ; R21 DC015744/DC/NIDCD NIH HHS/United States ; R21 NS093537/NS/NINDS NIH HHS/United States ; }, mesh = {Analgesia ; Analgesics, Opioid/*pharmacology ; Animals ; Conditioning (Psychology) ; Female ; GTP-Binding Proteins/metabolism ; Inflammation ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Morphine/pharmacology ; Neurons/metabolism ; Periaqueductal Gray/metabolism ; RGS Proteins/*antagonists & inhibitors/metabolism ; Sequence Analysis, RNA ; Wnt Proteins/metabolism ; *Wnt Signaling Pathway ; beta Catenin/metabolism ; }, abstract = {Regulator of G protein signaling z1 (RGSz1), a member of the RGS family of proteins, is present in several networks expressing mu opioid receptors (MOPRs). By using genetic mouse models for global or brain region-targeted manipulations of RGSz1 expression, we demonstrated that the suppression of RGSz1 function increases the analgesic efficacy of MOPR agonists in male and female mice and delays the development of morphine tolerance while decreasing the sensitivity to rewarding and locomotor activating effects. Using biochemical assays and next-generation RNA sequencing, we identified a key role of RGSz1 in the periaqueductal gray (PAG) in morphine tolerance. Chronic morphine administration promotes RGSz1 activity in the PAG, which in turn modulates transcription mediated by the Wnt/β-catenin signaling pathway to promote analgesic tolerance to morphine. Conversely, the suppression of RGSz1 function stabilizes Axin2-Gαz complexes near the membrane and promotes β-catenin activation, thereby delaying the development of analgesic tolerance. These data show that the regulation of RGS complexes, particularly those involving RGSz1-Gαz, represents a promising target for optimizing the analgesic actions of opioids without increasing the risk of dependence or addiction.}, } @article {pmid29440402, year = {2018}, author = {Grébert, T and Doré, H and Partensky, F and Farrant, GK and Boss, ES and Picheral, M and Guidi, L and Pesant, S and Scanlan, DJ and Wincker, P and Acinas, SG and Kehoe, DM and Garczarek, L}, title = {Light color acclimation is a key process in the global ocean distribution of Synechococcus cyanobacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2010-E2019}, pmid = {29440402}, issn = {1091-6490}, mesh = {*Acclimatization ; Chlorophyll/chemistry ; Color ; Computer Simulation ; Cyanobacteria/*genetics ; Ecosystem ; Ecotype ; Light ; Likelihood Functions ; Metagenome ; *Oceans and Seas ; Photosynthesis/physiology ; Phycobilisomes/*physiology ; Phylogeny ; Pigmentation ; Seawater/*microbiology ; Synechococcus/*genetics ; }, abstract = {Marine Synechococcus cyanobacteria are major contributors to global oceanic primary production and exhibit a unique diversity of photosynthetic pigments, allowing them to exploit a wide range of light niches. However, the relationship between pigment content and niche partitioning has remained largely undetermined due to the lack of a single-genetic marker resolving all pigment types (PTs). Here, we developed and employed a robust method based on three distinct marker genes (cpcBA, mpeBA, and mpeW) to estimate the relative abundance of all known Synechococcus PTs from metagenomes. Analysis of the Tara Oceans dataset allowed us to reveal the global distribution of Synechococcus PTs and to define their environmental niches. Green-light specialists (PT 3a) dominated in warm, green equatorial waters, whereas blue-light specialists (PT 3c) were particularly abundant in oligotrophic areas. Type IV chromatic acclimaters (CA4-A/B), which are able to dynamically modify their light absorption properties to maximally absorb green or blue light, were unexpectedly the most abundant PT in our dataset and predominated at depth and high latitudes. We also identified populations in which CA4 might be nonfunctional due to the lack of specific CA4 genes, notably in warm high-nutrient low-chlorophyll areas. Major ecotypes within clades I-IV and CRD1 were preferentially associated with a particular PT, while others exhibited a wide range of PTs. Altogether, this study provides important insights into the ecology of Synechococcus and highlights the complex interactions between vertical phylogeny, pigmentation, and environmental parameters that shape Synechococcus community structure and evolution.}, } @article {pmid29440401, year = {2018}, author = {Nerem, RS and Beckley, BD and Fasullo, JT and Hamlington, BD and Masters, D and Mitchum, GT}, title = {Climate-change-driven accelerated sea-level rise detected in the altimeter era.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2022-2025}, pmid = {29440401}, issn = {1091-6490}, abstract = {Using a 25-y time series of precision satellite altimeter data from TOPEX/Poseidon, Jason-1, Jason-2, and Jason-3, we estimate the climate-change-driven acceleration of global mean sea level over the last 25 y to be 0.084 ± 0.025 mm/y2 Coupled with the average climate-change-driven rate of sea level rise over these same 25 y of 2.9 mm/y, simple extrapolation of the quadratic implies global mean sea level could rise 65 ± 12 cm by 2100 compared with 2005, roughly in agreement with the Intergovernmental Panel on Climate Change (IPCC) 5th Assessment Report (AR5) model projections.}, } @article {pmid29440400, year = {2018}, author = {Markham, KA and Palmer, CM and Chwatko, M and Wagner, JM and Murray, C and Vazquez, S and Swaminathan, A and Chakravarty, I and Lynd, NA and Alper, HS}, title = {Rewiring Yarrowia lipolytica toward triacetic acid lactone for materials generation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2096-2101}, pmid = {29440400}, issn = {1091-6490}, mesh = {Gene Expression Regulation, Plant/*physiology ; Genetic Engineering/*methods ; Molecular Structure ; Oxidation-Reduction ; Pyrones/chemistry/*metabolism ; Pyruvates/metabolism ; Yarrowia/genetics/*metabolism ; }, abstract = {Polyketides represent an extremely diverse class of secondary metabolites often explored for their bioactive traits. These molecules are also attractive building blocks for chemical catalysis and polymerization. However, the use of polyketides in larger scale chemistry applications is stymied by limited titers and yields from both microbial and chemical production. Here, we demonstrate that an oleaginous organism (specifically, Yarrowia lipolytica) can overcome such production limitations owing to a natural propensity for high flux through acetyl-CoA. By exploring three distinct metabolic engineering strategies for acetyl-CoA precursor formation, we demonstrate that a previously uncharacterized pyruvate bypass pathway supports increased production of the polyketide triacetic acid lactone (TAL). Ultimately, we establish a strain capable of producing over 35% of the theoretical conversion yield to TAL in an unoptimized tube culture. This strain also obtained an averaged maximum titer of 35.9 ± 3.9 g/L with an achieved maximum specific productivity of 0.21 ± 0.03 g/L/h in bioreactor fermentation. Additionally, we illustrate that a β-oxidation-related overexpression (PEX10) can support high TAL production and is capable of achieving over 43% of the theoretical conversion yield under nitrogen starvation in a test tube. Next, through use of this bioproduct, we demonstrate the utility of polyketides like TAL to modify commodity materials such as poly(epichlorohydrin), resulting in an increased molecular weight and shift in glass transition temperature. Collectively, these findings establish an engineering strategy enabling unprecedented production from a type III polyketide synthase as well as establish a route through O-functionalization for converting polyketides into new materials.}, } @article {pmid29440399, year = {2018}, author = {Hochstein, R and Bollschweiler, D and Dharmavaram, S and Lintner, NG and Plitzko, JM and Bruinsma, R and Engelhardt, H and Young, MJ and Klug, WS and Lawrence, CM}, title = {Structural studies of Acidianus tailed spindle virus reveal a structural paradigm used in the assembly of spindle-shaped viruses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2120-2125}, pmid = {29440399}, issn = {1091-6490}, mesh = {Archaeal Viruses/physiology/*ultrastructure ; Capsid Proteins/genetics/metabolism/*ultrastructure ; Gene Expression Regulation, Viral ; Genome, Viral ; Models, Molecular ; Protein Conformation ; Protein Subunits ; Virus Assembly/*physiology ; }, abstract = {The spindle-shaped virion morphology is common among archaeal viruses, where it is a defining characteristic of many viral families. However, structural heterogeneity intrinsic to spindle-shaped viruses has seriously hindered efforts to elucidate the molecular architecture of these lemon-shaped capsids. We have utilized a combination of cryo-electron microscopy and X-ray crystallography to study Acidianus tailed spindle virus (ATSV). These studies reveal the architectural principles that underlie assembly of a spindle-shaped virus. Cryo-electron tomography shows a smooth transition from the spindle-shaped capsid into the tubular-shaped tail and allows low-resolution structural modeling of individual virions. Remarkably, higher-dose 2D micrographs reveal a helical surface lattice in the spindle-shaped capsid. Consistent with this, crystallographic studies of the major capsid protein reveal a decorated four-helix bundle that packs within the crystal to form a four-start helical assembly with structural similarity to the tube-shaped tail structure of ATSV and other tailed, spindle-shaped viruses. Combined, this suggests that the spindle-shaped morphology of the ATSV capsid is formed by a multistart helical assembly with a smoothly varying radius and allows construction of a pseudoatomic model for the lemon-shaped capsid that extends into a tubular tail. The potential advantages that this novel architecture conveys to the life cycle of spindle-shaped viruses, including a role in DNA ejection, are discussed.}, } @article {pmid29440398, year = {2018}, author = {He, J and Ford, HC and Carroll, J and Douglas, C and Gonzales, E and Ding, S and Fearnley, IM and Walker, JE}, title = {Assembly of the membrane domain of ATP synthase in human mitochondria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {2988-2993}, pmid = {29440398}, issn = {1091-6490}, support = {MC_EX_MR/M009858/1//Medical Research Council/United Kingdom ; }, mesh = {CRISPR-Cas Systems ; Cell Line ; Cell Proliferation ; Gene Expression Regulation, Enzymologic ; Humans ; Mitochondrial Membranes/*enzymology ; Mitochondrial Proton-Translocating ATPases/genetics/*metabolism ; Models, Molecular ; Mutation ; Oxygen Consumption ; Protein Conformation ; Protein Subunits ; }, abstract = {The ATP synthase in human mitochondria is a membrane-bound assembly of 29 proteins of 18 kinds. All but two membrane components are encoded in nuclear genes, synthesized on cytoplasmic ribosomes, and imported into the matrix of the organelle, where they are assembled into the complex with ATP6 and ATP8, the products of overlapping genes in mitochondrial DNA. Disruption of individual human genes for the nuclear-encoded subunits in the membrane portion of the enzyme leads to the formation of intermediate vestigial ATPase complexes that provide a description of the pathway of assembly of the membrane domain. The key intermediate complex consists of the F1-c8 complex inhibited by the ATPase inhibitor protein IF1 and attached to the peripheral stalk, with subunits e, f, and g associated with the membrane domain of the peripheral stalk. This intermediate provides the template for insertion of ATP6 and ATP8, which are synthesized on mitochondrial ribosomes. Their association with the complex is stabilized by addition of the 6.8 proteolipid, and the complex is coupled to ATP synthesis at this point. A structure of the dimeric yeast Fo membrane domain is consistent with this model of assembly. The human 6.8 proteolipid (yeast j subunit) locks ATP6 and ATP8 into the membrane assembly, and the monomeric complexes then dimerize via interactions between ATP6 subunits and between 6.8 proteolipids (j subunits). The dimers are linked together back-to-face by DAPIT (diabetes-associated protein in insulin-sensitive tissue; yeast subunit k), forming long oligomers along the edges of the cristae.}, } @article {pmid29440397, year = {2018}, author = {Schneider-Hohendorf, T and Görlich, D and Savola, P and Kelkka, T and Mustjoki, S and Gross, CC and Owens, GC and Klotz, L and Dornmair, K and Wiendl, H and Schwab, N}, title = {Sex bias in MHC I-associated shaping of the adaptive immune system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2168-2173}, pmid = {29440397}, issn = {1091-6490}, mesh = {Adaptive Immunity/*genetics/*physiology ; Adult ; Female ; Genes, MHC Class I/*physiology ; Humans ; Male ; Sex Factors ; }, abstract = {HLA associations, T cell receptor (TCR) repertoire bias, and sex bias have independently been shown for many diseases. While some immunological differences between the sexes have been described, they do not fully explain bias in men toward many infections/cancers, and toward women in autoimmunity. Next-generation TCR variable beta chain (TCRBV) immunosequencing of 824 individuals was evaluated in a multiparametric analysis including HLA-A -B/MHC class I background, TCRBV usage, sex, age, ethnicity, and TCRBV selection/expansion dynamics. We found that HLA-associated shaping of TCRBV usage differed between the sexes. Furthermore, certain TCRBVs were selected and expanded in unison. Correlations between these TCRBV relationships and biochemical similarities in HLA-binding positions were different in CD8 T cells of patients with autoimmune diseases (multiple sclerosis and rheumatoid arthritis) compared with healthy controls. Within patients, men showed higher TCRBV relationship Spearman's rhos in relation to HLA-binding position similarities compared with women. In line with this, CD8 T cells of men with autoimmune diseases also showed higher degrees of TCRBV perturbation compared with women. Concerted selection and expansion of CD8 T cells in patients with autoimmune diseases, but especially in men, appears to be less dependent on high HLA-binding similarity than in CD4 T cells. These findings are consistent with studies attributing autoimmunity to processes of epitope spreading and expansion of low-avidity T cell clones and may have further implications for the interpretation of pathogenic mechanisms of infectious and autoimmune diseases with known HLA associations. Reanalysis of some HLA association studies, separating the data by sex, could be informative.}, } @article {pmid29440384, year = {2018}, author = {Ahluwalia, A and Brzozowska, IM and Hoa, N and Jones, MK and Tarnawski, AS}, title = {Melatonin signaling in mitochondria extends beyond neurons and neuroprotection: Implications for angiogenesis and cardio/gastroprotection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1942-E1943}, pmid = {29440384}, issn = {1091-6490}, support = {I01 BX000626/BX/BLRD VA/United States ; }, mesh = {*Melatonin ; Mitochondria ; Neurons ; *Neuroprotection ; Neuroprotective Agents ; Signal Transduction/drug effects ; }, } @article {pmid29440383, year = {2018}, author = {Suofu, Y and Carlisle, DL and Vilardaga, JP and Friedlander, RM}, title = {Reply to Ahluwalia et al.: Contributions of melatonin receptors are tissue-dependent.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1944}, pmid = {29440383}, issn = {1091-6490}, support = {R01 DK102495/DK/NIDDK NIH HHS/United States ; }, mesh = {*Melatonin ; *Receptors, Melatonin ; }, } @article {pmid29440382, year = {2018}, author = {Kirillova, A and Genikhovich, G and Pukhlyakova, E and Demilly, A and Kraus, Y and Technau, U}, title = {Germ-layer commitment and axis formation in sea anemone embryonic cell aggregates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1813-1818}, pmid = {29440382}, issn = {1091-6490}, mesh = {Animals ; Biological Evolution ; Cell Aggregation ; Ectoderm/cytology/embryology/metabolism ; Embryonic Development ; Gene Expression Regulation, Developmental ; Germ Layers/*cytology/embryology/metabolism ; Sea Anemones/cytology/*embryology/genetics/metabolism ; Signal Transduction ; Wnt Proteins/genetics/metabolism ; }, abstract = {Robust morphogenetic events are pivotal for animal embryogenesis. However, comparison of the modes of development of different members of a phylum suggests that the spectrum of developmental trajectories accessible for a species might be far broader than can be concluded from the observation of normal development. Here, by using a combination of microsurgery and transgenic reporter gene expression, we show that, facing a new developmental context, the aggregates of dissociated embryonic cells of the sea anemone Nematostella vectensis take an alternative developmental trajectory. The self-organizing aggregates rely on Wnt signals produced by the cells of the original blastopore lip organizer to form body axes but employ morphogenetic events typical for normal development of distantly related cnidarians to re-establish the germ layers. The reaggregated cells show enormous plasticity including the capacity of the ectodermal cells to convert into endoderm. Our results suggest that new developmental trajectories may evolve relatively easily when highly plastic embryonic cells face new constraints.}, } @article {pmid29440381, year = {2018}, author = {Luo, C and Borodin, O and Ji, X and Hou, S and Gaskell, KJ and Fan, X and Chen, J and Deng, T and Wang, R and Jiang, J and Wang, C}, title = {Azo compounds as a family of organic electrode materials for alkali-ion batteries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2004-2009}, pmid = {29440381}, issn = {1091-6490}, abstract = {Organic compounds are desirable for sustainable Li-ion batteries (LIBs), but the poor cycle stability and low power density limit their large-scale application. Here we report a family of organic compounds containing azo group (N=N) for reversible lithiation/delithiation. Azobenzene-4,4'-dicarboxylic acid lithium salt (ADALS) with an azo group in the center of the conjugated structure is used as a model azo compound to investigate the electrochemical behaviors and reaction mechanism of azo compounds. In LIBs, ADALS can provide a capacity of 190 mAh g-1 at 0.5 C (corresponding to current density of 95 mA g-1) and still retain 90%, 71%, and 56% of the capacity when the current density is increased to 2 C, 10 C, and 20 C, respectively. Moreover, ADALS retains 89% of initial capacity after 5,000 cycles at 20 C with a slow capacity decay rate of 0.0023% per cycle, representing one of the best performances in all organic compounds. Superior electrochemical behavior of ADALS is also observed in Na-ion batteries, demonstrating that azo compounds are universal electrode materials for alkali-ion batteries. The highly reversible redox chemistry of azo compounds to alkali ions was confirmed by density-functional theory (DFT) calculations. It provides opportunities for developing sustainable batteries.}, } @article {pmid29440380, year = {2018}, author = {Yates, K and Bi, K and Haining, WN and Cantor, H and Kim, HJ}, title = {Comparative transcriptome analysis reveals distinct genetic modules associated with Helios expression in intratumoral regulatory T cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2162-2167}, pmid = {29440380}, issn = {1091-6490}, support = {R01 AI037562/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Forkhead Transcription Factors/genetics/metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic/*physiology ; Luminescent Proteins/metabolism ; Melanoma/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Neoplasms, Experimental/*metabolism ; T-Lymphocytes, Regulatory/*physiology ; Transcription Factors/genetics/*metabolism ; }, abstract = {Regulatory T cells (Tregs) are key modulators of immune tolerance, capable of suppressing inflammatory immune responses and promoting nonlymphoid tissue homeostasis. Helios, a transcription factor (TF) that is selectively expressed by Tregs, has been shown to be essential for the maintenance of Treg lineage stability in the face of inflammatory conditions that include autoimmune disease and cancer. Helios-deficient Tregs within tumors acquire effector T cell function and contribute to immune responses against cancer. However, the underlying genetic basis of this Treg reprogramming is not well understood. Here, we report that Helios-deficient Tregs within the chronic inflammatory tumor microenvironment (TME) derepress genetic programs associated with T helper (Th) cell differentiation by up-regulating Th cell-associated TFs and effector cytokines. These genetic changes of Helios-deficient Tregs are most apparent in a Treg subpopulation with high affinity for self-antigens, as detected by both increased GITR/PD-1 expression and increased responsiveness to self-antigens. Their combined effects may promote a phenotype conversion of Tregs into effector T cells within the TME, where TCR engagement and costimulatory receptor expression by Tregs are increased. These data provide a genetic basis for the unstable phenotype of Helios-deficient Tregs within the inflammatory environment of tumors and suggest that immune milieu-dependent alterations in gene expression are a central feature of Treg conversion.}, } @article {pmid29440379, year = {2018}, author = {Zhao, Y and Liu, P and Zhang, N and Chen, J and Landegger, LD and Wu, L and Zhao, F and Zhao, Y and Zhang, Y and Zhang, J and Fujita, T and Stemmer-Rachamimov, A and Ferraro, GB and Liu, H and Muzikansky, A and Plotkin, SR and Stankovic, KM and Jain, RK and Xu, L}, title = {Targeting the cMET pathway augments radiation response without adverse effect on hearing in NF2 schwannoma models.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2077-E2084}, pmid = {29440379}, issn = {1091-6490}, support = {U01 CA224348/CA/NCI NIH HHS/United States ; R01 DC015824/DC/NIDCD NIH HHS/United States ; R01 CA129371/CA/NCI NIH HHS/United States ; R35 CA197743/CA/NCI NIH HHS/United States ; P01 CA080124/CA/NCI NIH HHS/United States ; R01 CA208205/CA/NCI NIH HHS/United States ; P50 CA165962/CA/NCI NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Animals ; Brain/metabolism ; DNA Damage ; Female ; Hearing ; Hearing Loss/*etiology ; Humans ; Male ; Mice ; Middle Aged ; Neurilemmoma/complications/radiotherapy ; Neurofibromatosis 2/*complications/*radiotherapy ; Neurofibromin 2/genetics ; Neuroma, Acoustic/*complications/*radiotherapy ; Organ Culture Techniques ; Proto-Oncogene Proteins c-met/*metabolism ; Radiotherapy ; Signal Transduction ; Young Adult ; }, abstract = {Neurofibromatosis type II (NF2) is a disease that needs new solutions. Vestibular schwannoma (VS) growth causes progressive hearing loss, and the standard treatment, including surgery and radiotherapy, can further damage the nerve. There is an urgent need to identify an adjunct therapy that, by enhancing the efficacy of radiation, can help lower the radiation dose and preserve hearing. The mechanisms underlying deafness in NF2 are still unclear. One of the major limitations in studying tumor-induced hearing loss is the lack of mouse models that allow hearing testing. Here, we developed a cerebellopontine angle (CPA) schwannoma model that faithfully recapitulates the tumor-induced hearing loss. Using this model, we discovered that cMET blockade by crizotinib (CRZ) enhanced schwannoma radiosensitivity by enhancing DNA damage, and CRZ treatment combined with low-dose radiation was as effective as high-dose radiation. CRZ treatment had no adverse effect on hearing; however, it did not affect tumor-induced hearing loss, presumably because cMET blockade did not change tumor hepatocyte growth factor (HGF) levels. This cMET gene knockdown study independently confirmed the role of the cMET pathway in mediating the effect of CRZ. Furthermore, we evaluated the translational potential of cMET blockade in human schwannomas. We found that human NF2-associated and sporadic VSs showed significantly elevated HGF expression and cMET activation compared with normal nerves, which correlated with tumor growth and cyst formation. Using organoid brain slice culture, cMET blockade inhibited the growth of patient-derived schwannomas. Our findings provide the rationale and necessary data for the clinical translation of combined cMET blockade with radiation therapy in patients with NF2.}, } @article {pmid29440378, year = {2018}, author = {Lijek, RS and Helble, JD and Olive, AJ and Seiger, KW and Starnbach, MN}, title = {Pathology after Chlamydia trachomatis infection is driven by nonprotective immune cells that are distinct from protective populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2216-2221}, pmid = {29440378}, issn = {1091-6490}, support = {R29 AI039558/AI/NIAID NIH HHS/United States ; R01 AI062827/AI/NIAID NIH HHS/United States ; F32 AI108144/AI/NIAID NIH HHS/United States ; R01 AI039558/AI/NIAID NIH HHS/United States ; U19 AI113187/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Chlamydia Infections/microbiology/*pathology ; Chlamydia trachomatis/*classification ; Female ; Genitalia, Female/microbiology/*pathology ; Mice ; Monocytes/physiology ; Neutrophils/physiology ; T-Lymphocytes ; }, abstract = {Infection with Chlamydia trachomatis drives severe mucosal immunopathology; however, the immune responses that are required for mediating pathology vs. protection are not well understood. Here, we employed a mouse model to identify immune responses required for C. trachomatis-induced upper genital tract pathology and to determine whether these responses are also required for bacterial clearance. In mice as in humans, immunopathology was characterized by extravasation of leukocytes into the upper genital tract that occluded luminal spaces in the uterus and ovaries. Flow cytometry identified these cells as neutrophils at early time points and CD4+ and CD8+ T cells at later time points. To determine what draws these cells to C. trachomatis-infected tissue, we measured the expression of 700 inflammation-related genes in the upper genital tract and found an up-regulation of many chemokines, including a node of interaction between CXCL9/10/11 and their common receptor CXCR3. Either depleting neutrophils or reducing T-cell numbers by CXCR3 blockade was sufficient to significantly ameliorate immunopathology but had no effect on bacterial burden, demonstrating that these responses are necessary for mucosal pathology but dispensable for C. trachomatis clearance. Therapies that specifically target these host responses may therefore prove useful in ameliorating C. trachomatis-induced pathology without exacerbating infection or transmission.}, } @article {pmid29440377, year = {2018}, author = {Bogliotti, YS and Wu, J and Vilarino, M and Okamura, D and Soto, DA and Zhong, C and Sakurai, M and Sampaio, RV and Suzuki, K and Izpisua Belmonte, JC and Ross, PJ}, title = {Efficient derivation of stable primed pluripotent embryonic stem cells from bovine blastocysts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2090-2095}, pmid = {29440377}, issn = {1091-6490}, support = {DP1 DK113616/DK/NIDDK NIH HHS/United States ; R01 HD070044/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Biomarkers ; Blastocyst/*physiology ; Cattle/*embryology ; Cell Culture Techniques/veterinary ; Cell Differentiation ; Cells, Cultured ; Cloning, Organism ; Embryo Culture Techniques/veterinary ; Embryonic Stem Cells/*physiology ; Epigenesis, Genetic ; Gene Expression Regulation, Developmental/physiology ; Nuclear Transfer Techniques/veterinary ; Pluripotent Stem Cells/*physiology ; }, abstract = {Embryonic stem cells (ESCs) are derived from the inner cell mass of preimplantation blastocysts. From agricultural and biomedical perspectives, the derivation of stable ESCs from domestic ungulates is important for genomic testing and selection, genome engineering, and modeling human diseases. Cattle are one of the most important domestic ungulates that are commonly used for food and bioreactors. To date, however, it remains a challenge to produce stable pluripotent bovine ESC lines. Employing a culture system containing fibroblast growth factor 2 and an inhibitor of the canonical Wnt-signaling pathway, we derived pluripotent bovine ESCs (bESCs) with stable morphology, transcriptome, karyotype, population-doubling time, pluripotency marker gene expression, and epigenetic features. Under this condition bESC lines were efficiently derived (100% in optimal conditions), were established quickly (3-4 wk), and were simple to propagate (by trypsin treatment). When used as donors for nuclear transfer, bESCs produced normal blastocyst rates, thereby opening the possibility for genomic selection, genome editing, and production of cattle with high genetic value.}, } @article {pmid29440376, year = {2018}, author = {de Oliveira, S and Nisbett, RE}, title = {Demographically diverse crowds are typically not much wiser than homogeneous crowds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2066-2071}, pmid = {29440376}, issn = {1091-6490}, mesh = {Computer Simulation ; *Demography ; *Group Processes ; Humans ; *Judgment ; Models, Theoretical ; *Psychology, Social ; }, abstract = {Averaging independent numerical judgments can be more accurate than the average individual judgment. This "wisdom of crowds" effect has been shown with large, diverse samples, but the layperson wishing to take advantage of this may only have access to the opinions of a small, more demographically homogeneous "convenience sample." How wise are homogeneous crowds relative to diverse crowds? In simulations and survey studies, we demonstrate three necessary conditions under which small socially diverse crowds can outperform socially homogeneous crowds: Social identity must predict judgment, the effect of social identity on judgment must be at least moderate in size, and the average estimates of the social groups in question must "bracket" the truth being judged. Seven survey studies suggest that these conditions are rarely met in real judgment tasks. Comparisons between the performances of diverse and homogeneous crowds further confirm that social diversity can make crowds wiser but typically by a very small margin.}, } @article {pmid29440070, year = {2018}, author = {Wek, RC}, title = {Role of eIF2α Kinases in Translational Control and Adaptation to Cellular Stress.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a032870}, pmid = {29440070}, issn = {1943-0264}, abstract = {A central mechanism regulating translation initiation in response to environmental stress involves phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α). Phosphorylation of eIF2α causes inhibition of global translation, which conserves energy and facilitates reprogramming of gene expression and signaling pathways that help to restore protein homeostasis. Coincident with repression of protein synthesis, many gene transcripts involved in the stress response are not affected or are even preferentially translated in response to increased eIF2α phosphorylation by mechanisms involving upstream open reading frames (uORFs). This review highlights the mechanisms regulating eIF2α kinases, the role that uORFs play in translational control, and the impact that alteration of eIF2α phosphorylation by gene mutations or small molecule inhibitors can have on health and disease.}, } @article {pmid29440069, year = {2018}, author = {Chu, J and Pelletier, J}, title = {Therapeutic Opportunities in Eukaryotic Translation.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a032995}, pmid = {29440069}, issn = {1943-0264}, abstract = {The ability to block biological processes with selective small molecules provides advantages distinct from most other experimental approaches. These include rapid time to onset, swift reversibility, ability to probe activities in manners that cannot be accessed by genetic means, and the potential to be further developed as therapeutic agents. Small molecule inhibitors can also be used to alter expression and activity without affecting the stoichiometry of interacting partners. These tenets have been especially evident in the field of translation. Small molecule inhibitors were instrumental in enabling investigators to capture short-lived complexes and characterize specific steps of protein synthesis. In addition, several drugs that are the mainstay of modern antimicrobial drug therapy are potent inhibitors of prokaryotic translation. Currently, there is much interest in targeting eukaryotic translation as decades of research have revealed that deregulated protein synthesis in cancer cells represents a targetable vulnerability. In addition to being potential therapeutics, small molecules that manipulate translation have also been shown to influence cognitive processes such as memory. In this review, we focus on small molecule modulators that target the eukaryotic translation initiation apparatus and provide an update on their potential application to the treatment of disease.}, } @article {pmid29439838, year = {2018}, author = {Durão, P and Balbontín, R and Gordo, I}, title = {Evolutionary Mechanisms Shaping the Maintenance of Antibiotic Resistance.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {677-691}, doi = {10.1016/j.tim.2018.01.005}, pmid = {29439838}, issn = {1878-4380}, abstract = {Antibiotics target essential cellular functions but bacteria can become resistant by acquiring either exogenous resistance genes or chromosomal mutations. Resistance mutations typically occur in genes encoding essential functions; these mutations are therefore generally detrimental in the absence of drugs. However, bacteria can reduce this handicap by acquiring additional mutations, known as compensatory mutations. Genetic interactions (epistasis) either with the background or between resistances (in multiresistant bacteria) dramatically affect the fitness cost of antibiotic resistance and its compensation, therefore shaping dissemination of antibiotic resistance mutations. This Review summarizes current knowledge on the evolutionary mechanisms influencing maintenance of resistance mediated by chromosomal mutations, focusing on their fitness cost, compensatory evolution, epistasis, and the effect of the environment on these processes.}, } @article {pmid29439741, year = {2018}, author = {Xiong, W and Wang, Y and Sun, Y and Ma, L and Zeng, Q and Jiang, X and Li, A and Zeng, Z and Zhang, T}, title = {Antibiotic-mediated changes in the fecal microbiome of broiler chickens define the incidence of antibiotic resistance genes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {34}, pmid = {29439741}, issn = {2049-2618}, support = {31702290//the National Natural Science Foundation of China/International ; 31672608//the National Natural Science Foundation of China/International ; GRF7201/11E//Hong Kong/International ; }, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bacteria/*classification/drug effects/genetics/isolation & purification ; Bacterial Proteins/*genetics ; Bifidobacterium/classification/drug effects/genetics/isolation & purification ; Chickens ; Chlortetracycline/pharmacology ; *Drug Resistance, Bacterial ; Escherichia/classification/drug effects/genetics/isolation & purification ; Feces/*microbiology ; Gene Regulatory Networks ; Klebsiella/classification/drug effects/genetics/isolation & purification ; Metagenomics ; Microbiota/drug effects ; RNA, Ribosomal, 16S/genetics ; }, abstract = {BACKGROUND: Antimicrobial agents have been widely used in animal farms to prevent and treat animal diseases and to promote growth. Antimicrobial agents may change the bacterial community and enhance the resistome in animal feces. We used metagenome-wide analysis to investigate the changes in bacterial community, variations in antibiotic resistance genes (ARGs), and their bacterial hosts in the feces of broiler chickens over a full-treatment course of chlortetracycline at low and therapeutic dose levels.

RESULTS: The effects of chlortetracycline on resistome were dependent on the specific ARG subtypes and not simply the overall community-level ARGs. Therapeutic dose of chlortetracycline promoted the abundance of tetracycline resistance genes (tetA and tetW) and inhibited multidrug resistance genes (mdtA, mdtC, mdtK, ompR, and TolC). The therapeutic dose of chlortetracycline led to loss of Proteobacteria mainly due to the decrease of Escherichia/Shigella (from 72 to 58%). Inhibition of Escherichia by chlortetracycline was the primary reason for the decrease of genes resistant to multiple drugs in the therapeutic dose group. The ARG host Bifidobacterium were enriched due to tetW harbored by Bifidobacterium under chlortetracycline treatment. Escherichia was always the major host for multidrug resistance genes, whereas the primary host was changed from Escherichia to Klebsiella for aminoglycoside resistance genes with the treatment of therapeutic dose of chlortetracycline.

CONCLUSIONS: We provided the first metagenomic insights into antibiotic-mediated alteration of ARG-harboring bacterial hosts at community-wide level in chicken feces. These results indicated that the changes in the structure of antibiotic-induced feces microbial communities accompany changes in the abundance of bacterial hosts carrying specific ARGs in the feces microbiota. These findings will help to optimize therapeutic schemes for the effective treatment of antibiotic resistant pathogens in poultry farms. Resistome variations in faecal microbiome of chickens exposed to chlortetracycline.}, } @article {pmid29439737, year = {2018}, author = {Nantongo, JS and Odoi, JB and Abigaba, G and Gwali, S}, title = {Variability of phenolic and alkaloid content in different plant parts of Carissa edulis Vahl and Zanthoxylum chalybeum Engl.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {125}, pmid = {29439737}, issn = {1756-0500}, mesh = {Alkaloids/*chemistry ; Apocynaceae/*chemistry ; Phenols/*chemistry ; Plant Bark/*chemistry ; Plant Leaves/*chemistry ; Zanthoxylum/*chemistry ; }, abstract = {OBJECTIVE: The objective of the study was to investigate the relative abundance and effect of post-harvest treatment on total phenolics (TP) and total alkaloids in the leaves and bark of Carissa edulis and Zanthoxylum chalybeum, which would give an indication of the suitability of leaves as alternative sources of medicine in these plant species.

RESULTS: Results indicated higher levels of total phenolics than total alkaloids in both of the species under both freezing and air drying conditions. While more alkaloids were found in leaves compared to bark, there was no difference in abundance of phenols between the plant parts of both species. Air drying preserved more TPs than freezing and the opposite was true for alkaloids. For sustainability, leaves are recommended as an alternative source of medicine instead of the preferred root or stem bark. However, the choice of whether to dry or freeze will depend on the specific compound of interest. Assessment of spatial variability of medicinal properties is highly recommended.}, } @article {pmid29439731, year = {2018}, author = {Metwally, AA and Yang, J and Ascoli, C and Dai, Y and Finn, PW and Perkins, DL}, title = {MetaLonDA: a flexible R package for identifying time intervals of differentially abundant features in metagenomic longitudinal studies.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {32}, pmid = {29439731}, issn = {2049-2618}, support = {UL1TR002003//UIC CCTS/International ; U01 AI132898/AI/NIAID NIH HHS/United States ; UL1 TR002003/TR/NCATS NIH HHS/United States ; R01 HL138628/HL/NHLBI NIH HHS/United States ; U01AI132898//National Institute of Allergy and Infectious Diseases/International ; R01HL138628/HL/NHLBI NIH HHS/United States ; }, mesh = {Bacteroides/*classification/isolation & purification ; Bifidobacterium/*classification/isolation & purification ; Finland ; High-Throughput Nucleotide Sequencing ; Humans ; Infant ; Longitudinal Studies ; Metagenomics/*methods ; RNA, Ribosomal, 16S ; Russia ; Software ; }, abstract = {BACKGROUND: Microbial longitudinal studies are powerful experimental designs utilized to classify diseases, determine prognosis, and analyze microbial systems dynamics. In longitudinal studies, only identifying differential features between two phenotypes does not provide sufficient information to determine whether a change in the relative abundance is short-term or continuous. Furthermore, sample collection in longitudinal studies suffers from all forms of variability such as a different number of subjects per phenotypic group, a different number of samples per subject, and samples not collected at consistent time points. These inconsistencies are common in studies that collect samples from human subjects.

RESULTS: We present MetaLonDA, an R package that is capable of identifying significant time intervals of differentially abundant microbial features. MetaLonDA is flexible such that it can perform differential abundance tests despite inconsistencies associated with sample collection. Extensive experiments on simulated datasets quantitatively demonstrate the effectiveness of MetaLonDA with significant improvement over alternative methods. We applied MetaLonDA to the DIABIMMUNE cohort (https://pubs.broadinstitute.org/diabimmune) substantiating significant early lifetime intervals of exposure to Bacteroides and Bifidobacterium in Finnish and Russian infants. Additionally, we established significant time intervals during which novel differentially relative abundant microbial genera may contribute to aberrant immunogenicity and development of autoimmune disease.

CONCLUSION: MetaLonDA is computationally efficient and can be run on desktop machines. The identified differentially abundant features and their time intervals have the potential to distinguish microbial biomarkers that may be used for microbial reconstitution through bacteriotherapy, probiotics, or antibiotics. Moreover, MetaLonDA can be applied to any longitudinal count data such as metagenomic sequencing, 16S rRNA gene sequencing, or RNAseq. MetaLonDA is publicly available on CRAN (https://CRAN.R-project.org/package=MetaLonDA).}, } @article {pmid29439713, year = {2018}, author = {Subramanya, SH and Pai, V and Bairy, I and Nayak, N and Gokhale, S and Sathian, B}, title = {Potassium permanganate cleansing is an effective sanitary method for the reduction of bacterial bioload on raw Coriandrum sativum.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {124}, pmid = {29439713}, issn = {1756-0500}, mesh = {Aeromonas/drug effects/*isolation & purification ; Coriandrum/*microbiology ; Disinfectants/*pharmacology ; Food Contamination/*prevention & control ; Plant Leaves/*microbiology ; Potassium Permanganate/*pharmacology ; Salmonella/drug effects/*isolation & purification ; }, abstract = {OBJECTIVE: Raw vegetables including flowers, leaves, stems, and roots are important carriers of food borne pathogens. We evaluated the bacteriological contamination of unwashed coriander leaves, and effectiveness of cleansing with 0.1% potassium permanganate solution as decontamination method.

RESULTS: Significant bacterial contamination including pathogens like Salmonella species and Aeromonas species were isolated from unwashed coriander leaves. Decontamination with 0.1% potassium permanganate was found to be more effective than three steps wash with sterile water.}, } @article {pmid29439680, year = {2018}, author = {Tan, JS and Abbasiliasi, S and Kadkhodaei, S and Tam, YJ and Tang, TK and Lee, YY and Ariff, AB}, title = {Microtiter miniature shaken bioreactor system as a scale-down model for process development of production of therapeutic alpha-interferon2b by recombinant Escherichia coli.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {3}, pmid = {29439680}, issn = {1471-2180}, mesh = {Biomass ; Bioreactors/*microbiology ; Escherichia coli/genetics/growth & development/*metabolism ; Fermentation ; Industrial Microbiology/methods ; Interferon-alpha/*biosynthesis ; Kinetics ; Osmotic Pressure ; Oxygen ; Recombinant Proteins/biosynthesis/genetics ; Scattering, Radiation ; }, abstract = {BACKGROUND: Demand for high-throughput bioprocessing has dramatically increased especially in the biopharmaceutical industry because the technologies are of vital importance to process optimization and media development. This can be efficiently boosted by using microtiter plate (MTP) cultivation setup embedded into an automated liquid-handling system. The objective of this study was to establish an automated microscale method for upstream and downstream bioprocessing of α-IFN2b production by recombinant Escherichia coli. The extraction performance of α-IFN2b by osmotic shock using two different systems, automated microscale platform and manual extraction in MTP was compared.

RESULTS: The amount of α-IFN2b extracted using automated microscale platform (49.2 μg/L) was comparable to manual osmotic shock method (48.8 μg/L), but the standard deviation was 2 times lower as compared to manual osmotic shock method. Fermentation parameters in MTP involving inoculum size, agitation speed, working volume and induction profiling revealed that the fermentation conditions for the highest production of α-IFN2b (85.5 μg/L) was attained at inoculum size of 8%, working volume of 40% and agitation speed of 1000 rpm with induction at 4 h after the inoculation.

CONCLUSION: Although the findings at MTP scale did not show perfect scalable results as compared to shake flask culture, but microscale technique development would serve as a convenient and low-cost solution in process optimization for recombinant protein.}, } @article {pmid29439676, year = {2018}, author = {Twyman, H and Andersson, S and Mundy, NI}, title = {Evolution of CYP2J19, a gene involved in colour vision and red coloration in birds: positive selection in the face of conservation and pleiotropy.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {22}, pmid = {29439676}, issn = {1471-2148}, support = {DTP//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Birds/*genetics ; Color Vision/*genetics ; *Conserved Sequence ; Cytochrome P-450 Enzyme System/*genetics ; *Evolution, Molecular ; Genetic Loci ; *Genetic Pleiotropy ; Genome ; Pigmentation/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: Exaggerated signals, such as brilliant colours, are usually assumed to evolve through antagonistic coevolution between senders and receivers, but the underlying genetic mechanisms are rarely known. Here we explore a recently identified "redness gene", CYP2J19, that is highly interesting in this context since it encodes a carotenoid-modifying enzyme (a C4 ketolase involved in both colour signalling and colour discrimination in the red (long wavelength) spectral region.) RESULTS: A single full-length CYP2J19 was retrieved from 43 species out of 70 avian genomes examined, representing all major avian clades. In addition, CYP2J19 sequences from 13 species of weaverbirds (Ploceidae), seven of which have red C4-ketocarotenoid coloration were analysed. Despite the conserved retinal function and pleiotropy of CYP2J19, analyses indicate that the gene has been positively selected throughout the radiation of birds, including sites within functional domains described in related CYP (cytochrome P450) loci. Analyses of eight further CYP loci across 25 species show that positive selection is common in this gene family in birds. There was no evidence for a change in selection pressure on CYP2J19 following co-option for red coloration in the weaverbirds.

CONCLUSIONS: The results presented here are consistent with an ancestral conserved function of CYP2J19 in the pigmentation of red retinal oil droplets used for colour vision, and its subsequent co-option for red integumentary coloration. The cause of positive selection on CYP2J19 is unclear, but may be partly related to compensatory mutations related to selection at the adjacent gene CYP2J40.}, } @article {pmid29439665, year = {2018}, author = {Feng, G and Xie, T and Wang, X and Bai, J and Tang, L and Zhao, H and Wei, W and Wang, M and Zhao, Y}, title = {Metagenomic analysis of microbial community and function involved in cd-contaminated soil.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {11}, pmid = {29439665}, issn = {1471-2180}, mesh = {Amino Acids/metabolism ; Bacteria/classification/*drug effects/genetics/metabolism ; Biodiversity ; Cadmium/metabolism/*toxicity ; China ; DNA, Bacterial ; Environmental Pollution ; Fatty Acids/metabolism ; Metabolic Networks and Pathways ; *Metagenomics ; Metals, Heavy/metabolism ; Microbial Consortia/*drug effects ; Nucleotides/metabolism ; Open Reading Frames ; Phylogeny ; Soil/chemistry ; *Soil Microbiology ; Soil Pollutants/metabolism/*toxicity ; }, abstract = {BACKGROUND: Soil contaminated with the heavy metal Cadmium (Cd) is a widespread problem in many parts of the world. Based on metagenomic analysis, we investigated the functional potential and structural diversity of the microbial community in Cd-contaminated and non-contaminated soil samples and we explored the associated metabolic pathway network in cluster of orthologous groups (COG) and Kyoto Encyclopedia of Genes and Genomes (KEGG).

RESULTS: The results showed that microorganisms in these soils were quite abundant, and many of them possessed numerous physiological functions. However, Cd-contamination has the potential to reduce the microbial diversity and further alter the community structure in the soil. Notably, function analysis of the crucial microorganisms (e. g. Proteobacteria, Sulfuricella and Thiobacillus) indicated that these bacteria and their corresponding physiological functions were important for the community to cope with Cd pollution. The COG annotation demonstrated that the predominant category was the microbial metabolism cluster in both soil samples, while the relative abundance of metabolic genes was increased in the Cd-contaminated soil. The KEGG annotation results exhibited that the non-contaminated soil had more genes, pathways, modules, orthologies and enzymes involved in metabolic pathways of microbial communities than the Cd-contaminated soil. The relative abundance of some dominant KEGG pathways increased in the Cd contaminated soil, and they were mostly enriched to the metabolism, biosynthesis and degradation of amino acids, fatty acids and nucleotides, which was related to Cd tolerance of the microorganisms.

CONCLUSIONS: Cd-contamination can decrease the taxonomic species of microbes in soil and change the soil microbial composition. The functional pathways involved in the soil change with microbial structure variation, many of which are related to the heavy metal tolerance of soil microbes. The Cd-contaminated soil microbes is a potential resource for exploring cadmium resistant or tolerant bacteria.}, } @article {pmid29439663, year = {2018}, author = {Wu, J and Dai, W and Wu, L and Wang, J}, title = {SALP, a new single-stranded DNA library preparation method especially useful for the high-throughput characterization of chromatin openness states.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {143}, pmid = {29439663}, issn = {1471-2164}, support = {61571119//National Natural Science Foundation of China/International ; }, mesh = {Cell Line ; Chromatin/*genetics ; DNA, Single-Stranded/*genetics ; *Gene Library ; HEK293 Cells ; HeLa Cells ; Hep G2 Cells ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Models, Genetic ; Oligonucleotides/genetics ; }, abstract = {BACKGROUND: Next-generation sequencing (NGS) is fundamental to the current biological and biomedical research. Construction of sequencing library is a key step of NGS. Therefore, various library construction methods have been explored. However, the current methods are still limited by some shortcomings.

RESULTS: This study developed a new NGS library construction method, Single strand Adaptor Library Preparation (SALP), by using a novel single strand adaptor (SSA). SSA is a double-stranded oligonucleotide with a 3' overhang of 3 random nucleotides, which can be efficiently ligated to the 3' end of single strand DNA by T4 DNA ligase. SALP can be started with any denatured DNA fragments such as those sheared by Tn5 tagmentation, enzyme digestion and sonication. When started with Tn5-tagmented chromatin, SALP can overcome a key limitation of ATAC-seq and become a high-throughput NGS library construction method, SALP-seq, which can be used to comparatively characterize the chromatin openness state of multiple cells unbiasly. In this way, this study successfully characterized the comparative chromatin openness states of four different cell lines, including GM12878, HepG2, HeLa and 293T, with SALP-seq. Similarly, this study also successfully characterized the chromatin openness states of HepG2 cells with SALP-seq by using 105 to 500 cells.

CONCLUSIONS: This study developed a new NGS library construction method, SALP, by using a novel kind of single strand adaptor (SSA), which should has wide applications in the future due to its unique performance.}, } @article {pmid29439662, year = {2018}, author = {Yuan, Z and Liu, S and Zhou, T and Tian, C and Bao, L and Dunham, R and Liu, Z}, title = {Comparative genome analysis of 52 fish species suggests differential associations of repetitive elements with their living aquatic environments.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {141}, pmid = {29439662}, issn = {1471-2164}, support = {2015-67015-22907//National Institute of Food and Agriculture/International ; }, mesh = {Animals ; Aquatic Organisms/classification/*genetics ; DNA Transposable Elements/genetics ; Ecosystem ; Fishes/classification/*genetics ; Fresh Water ; Genome/genetics ; Genomics/*methods ; Phylogeny ; Repetitive Sequences, Nucleic Acid/*genetics ; Seawater ; Species Specificity ; }, abstract = {BACKGROUND: Repetitive elements make up significant proportions of genomes. However, their roles in evolution remain largely unknown. To provide insights into the roles of repetitive elements in fish genomes, we conducted a comparative analysis of repetitive elements of 52 fish species in 22 orders in relation to their living aquatic environments.

RESULTS: The proportions of repetitive elements in various genomes were found to be positively correlated with genome sizes, with a few exceptions. More importantly, there appeared to be specific enrichment between some repetitive element categories with species habitat. Specifically, class II transposons appear to be more abundant in freshwater bony fish than in marine bony fish when phylogenetic relationship is not considered. In contrast, marine bony fish harbor more tandem repeats than freshwater species. In addition, class I transposons appear to be more abundant in primitive species such as cartilaginous fish and lamprey than in bony fish.

CONCLUSIONS: The enriched association of specific categories of repetitive elements with fish habitats suggests the importance of repetitive elements in genome evolution and their potential roles in fish adaptation to their living environments. However, due to the restriction of the limited sequenced species, further analysis needs to be done to alleviate the phylogenetic biases.}, } @article {pmid29439661, year = {2018}, author = {Carignano, HA and Roldan, DL and Beribe, MJ and Raschia, MA and Amadio, A and Nani, JP and Gutierrez, G and Alvarez, I and Trono, K and Poli, MA and Miretti, MM}, title = {Genome-wide scan for commons SNPs affecting bovine leukemia virus infection level in dairy cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {142}, pmid = {29439661}, issn = {1471-2164}, support = {37143//MINCyT-FONCyT PAE/International ; 1131033//INTA PNBIO/International ; D3.10.28//FAO-IAEA CRP/International ; }, mesh = {Animals ; Cattle ; Cattle Diseases/*genetics/virology ; Enzootic Bovine Leukosis/*genetics/virology ; Female ; Genomics/*methods ; Haplotypes ; Leukemia Virus, Bovine/physiology ; Leukocytes/metabolism/virology ; Linkage Disequilibrium ; *Polymorphism, Single Nucleotide ; Proviruses/physiology ; Transcription Factors/genetics ; Viral Load ; }, abstract = {BACKGROUND: Bovine leukemia virus (BLV) infection is omnipresent in dairy herds causing direct economic losses due to trade restrictions and lymphosarcoma-related deaths. Milk production drops and increase in the culling rate are also relevant and usually neglected. The BLV provirus persists throughout a lifetime and an inter-individual variation is observed in the level of infection (LI) in vivo. High LI is strongly correlated with disease progression and BLV transmission among herd mates. In a context of high prevalence, classical control strategies are economically prohibitive. Alternatively, host genomics studies aiming to dissect loci associated with LI are potentially useful tools for genetic selection programs tending to abrogate the viral spreading. The LI was measured through the proviral load (PVL) set-point and white blood cells (WBC) counts. The goals of this work were to gain insight into the contribution of SNPs (bovine 50KSNP panel) on LI variability and to identify genomics regions underlying this trait.

RESULTS: We quantified anti-p24 response and total leukocytes count in peripheral blood from 1800 cows and used these to select 800 individuals with extreme phenotypes in WBCs and PVL. Two case-control genomic association studies using linear mixed models (LMMs) considering population stratification were performed. The proportion of the variance captured by all QC-passed SNPs represented 0.63 (SE ± 0.14) of the phenotypic variance for PVL and 0.56 (SE ± 0.15) for WBCs. Overall, significant associations (Bonferroni's corrected -log10p > 5.94) were shared for both phenotypes by 24 SNPs within the Bovine MHC. Founder haplotypes were used to measure the linkage disequilibrium (LD) extent (r2 = 0.22 ± 0.27 at inter-SNP distance of 25-50 kb). The SNPs and LD blocks indicated genes potentially associated with LI in infected cows: i.e. relevant immune response related genes (DQA1, DRB3, BOLA-A, LTA, LTB, TNF, IER3, GRP111, CRISP1), several genes involved in cell cytoskeletal reorganization (CD2AP, PKHD1, FLOT1, TUBB5) and modelling of the extracellular matrix (TRAM2, TNXB). Host transcription factors (TFs) were also highlighted (TFAP2D; ABT1, GCM1, PRRC2A).

CONCLUSIONS: Data obtained represent a step forward to understand the biology of BLV-bovine interaction, and provide genetic information potentially applicable to selective breeding programs.}, } @article {pmid29439658, year = {2018}, author = {Wang, W and Penland, L and Gokce, O and Croote, D and Quake, SR}, title = {High fidelity hypothermic preservation of primary tissues in organ transplant preservative for single cell transcriptome analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {140}, pmid = {29439658}, issn = {1471-2164}, support = {5UH2AR06767603/NH/NIH HHS/United States ; }, mesh = {Animals ; Cell Survival/genetics ; Cryopreservation/*methods ; Gene Expression Profiling/methods ; Gene Ontology ; Kidney/cytology/*metabolism ; Kidney Transplantation/*methods ; Mice ; Reproducibility of Results ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/*methods ; *Transcriptome ; }, abstract = {BACKGROUND: High-fidelity preservation strategies for primary tissues are in great demand in the single cell RNAseq community. A reliable method would greatly expand the scope of feasible multi-site collaborations and maximize the utilization of technical expertise. When choosing a method, standardizability and fidelity are important factors to consider due to the susceptibility of single-cell RNAseq analysis to technical noise. Existing approaches such as cryopreservation and chemical fixation are less than ideal for failing to satisfy either or both of these standards.

RESULTS: Here we propose a new strategy that leverages preservation schemes developed for organ transplantation. We evaluated the strategy by storing intact mouse kidneys in organ transplant preservative solution at hypothermic temperature for up to 4 days (6 h, 1, 2, 3, and 4 days), and comparing the quality of preserved and fresh samples using FACS and single cell RNAseq. We demonstrate that the strategy effectively maintained cell viability, transcriptome integrity, cell population heterogeneity, and transcriptome landscape stability for samples after up to 3 days of preservation. The strategy also facilitated the definition of the diverse spectrum of kidney resident immune cells, to our knowledge the first time at single cell resolution.

CONCLUSIONS: Hypothermic storage of intact primary tissues in organ transplant preservative maintains the quality and stability of the transcriptome of cells for single cell RNAseq analysis. The strategy is readily generalizable to primary specimens from other tissue types for single cell RNAseq analysis.}, } @article {pmid29439656, year = {2018}, author = {Li, BJ and Wang, JY and Liu, ZJ and Zhuang, XY and Huang, JX}, title = {Genetic diversity and ex situ conservation of Loropetalum subcordatum, an endangered species endemic to China.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {12}, pmid = {29439656}, issn = {1471-2156}, abstract = {BACKGROUND: Loropetalum subcordatum is an endangered species endemic to China that is characterized by narrow distribution, small population size, and delayed fertilization. However, the genetic diversity of the entire extant natural and ex situ populations has not been assessed to date. In this study, we evaluated the genetic diversity and structure of six natural populations and a single ex situ population (the only known ex situ population of L. subcordatum) using sequence-related amplified polymorphism data.

RESULTS: In total, 553 reliable DNA bands, of which 359 (63.28%) were polymorphic, were amplified by polymerase chain reaction with combinations of 15 primers. Low average gene diversity within populations and high genetic differentiation were detected in L. subcordatum. A Mantel test demonstrated that there was a positive correlation between genetic and geographic distances, indicating that significant genetic divergence was likely the result of geographic isolation among natural populations. Furthermore, based on genetic structure patterns, populations of L. subcordatum were divided into three clusters. Group 1 was composed of specimens from Libo, Guizhou Province (GZ) and Huanjiang, Guangxi Zhuang Autonomous Region (GX). Group 2 was composed of Mt. Wuguishan, Guangdong Province (GD). Group 3 was composed of three populations in Hong Kong Special Administrative Region. Additionally, clonal reproduction probably existed in GD population. According to the genetic information analysis and field survey, the ex situ population did not match its source population (GD) in terms of genetics, and its habitat was different from the original natural habitat. We observed that a few individual GD seeds were needed to improve ZS ex situ in the future.

CONCLUSIONS: Compared to previous SRAP-based studies of endangered plants, L. subcordatum had extremely low average gene diversity within populations and high genetic differentiation among populations. At present, the unique ex situ population has not been successful due to non-representative samples being taken, a smaller population size, and man-made changes in habitat. Potential strategies are suggested to improve the conservation of this species.}, } @article {pmid29439649, year = {2018}, author = {Killian, JA and Topiwala, TM and Pelletier, AR and Frankhouser, DE and Yan, PS and Bundschuh, R}, title = {FuSpot: a web-based tool for visual evaluation of fusion candidates.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {139}, pmid = {29439649}, issn = {1471-2164}, support = {Pelotonia Undergraduate Research Fellowship//Pelotonia, Ohio State University/International ; T32GM068412/GM/NIGMS NIH HHS/United States ; An allocation of computing time//Ohio Supercomputer Center/International ; Pelotonia Graduate Research Fellowship//Pelotonia, Ohio State University/International ; R50 CA211524/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; P30CA016058/CA/NCI NIH HHS/United States ; T32 GM068412/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Computational Biology/*methods ; Genomics/methods ; Humans ; Information Storage and Retrieval ; Neoplasms/*genetics ; *Oncogene Fusion ; Oncogene Proteins, Fusion/*genetics ; *Software ; }, abstract = {BACKGROUND: Gene fusions often occur in cancer cells and in some cases are the main driver of oncogenesis. Correct identification of oncogenic gene fusions thus has implications for targeted cancer therapy. Recognition of this potential has led to the development of a myriad of sequencing-based fusion detection tools. However, given the same input, many of these detectors will find different fusion points or claim different sets of supporting data. Furthermore, the rate at which these tools falsely detect fusion events in data varies greatly. This discrepancy between tools underscores the fact that computation algorithms still cannot perfectly evaluate evidence; especially when provided with small amounts of supporting data as is typical in fusion detection. We assert that when evidence is provided in an easily digestible form, humans are more proficient in identifying true positives from false positives.

RESULTS: We have developed a web tool that, given the genomic coordinates of a candidate fusion breakpoint, will extract fusion and non-fusion reads adjacent to the fusion point from partner transcripts, and color code reads by transcript origin and read orientation for ease of intuitive inspection by the user. Fusion partner transcript read alignments are performed using a novel variant of the Smith-Waterman algorithm.

CONCLUSIONS: Combined with dynamic filtering parameters, the visualization provided by our tool introduces a powerful new investigative step that allows researchers to comprehensively evaluate fusion evidence. Additionally, this allows quick identification of false positives that may deceive most fusion detectors, thus eliminating unnecessary gene fusion validation. We apply our visualization tool to publicly available datasets and provide examples of true as well as false positives reported by open source fusion detection tools.}, } @article {pmid29439271, year = {2018}, author = {Fanelli, F and Baronio, F and Ortolano, R and Mezzullo, M and Cassio, A and Pagotto, U and Balsamo, A}, title = {Normative Basal Values of Hormones and Proteins of Gonadal and Adrenal Functions from Birth to Adulthood.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {50-94}, doi = {10.1159/000486840}, pmid = {29439271}, issn = {1661-5433}, mesh = {Adolescent ; Adrenal Glands/*metabolism ; Adult ; Child ; Child, Preschool ; Female ; Gonads/*metabolism ; Hormones/*blood ; Humans ; Infant ; Infant, Newborn ; Male ; Middle Aged ; Proteins/*metabolism ; Reference Values ; Young Adult ; }, abstract = {In clinical practice, it is fundamental to compare the results of hormonal examinations obtained in the laboratory with reliable reference values. This is particularly difficult when faced with rare conditions, such as disorders of sex development, where not routinely assayed peptide hormones as well as intermediate steroid metabolites are often needed and local reliable reference values are not available. There are considerable differences among techniques and assays used in clinical and research laboratories. In fact, laboratory hormonology is undergoing a critical transition between techniques for quantitative determination: established immunoassays and mass spectrometry. Harmonizing results from different laboratories is a major challenge along the path leading to the establishment of consensus reference intervals for steroid hormones. Most of the efforts are being concentrated on testosterone, with very encouraging results being provided by the harmonization of liquid chromatography-tandem mass spectrometry results. However, this goal is still far from being achieved for the other steroid and small-molecule hormones, and a much more challenging perspective is foreseeable for protein hormones. In addition to technical issues, the importance of the definition and of the characterization of the reference population as well as sampling and processing methodology should not be underestimated, as these aspects may impact on hormonal axis and compound stability. The aim of the present review is to provide a comprehensive overview of the circulating reference values in basal condition of the hormones and proteins involved in sex development reported to date in the peer-reviewed literature. We present a series of tables where we have collected the reference intervals for each specific hormone and protein.}, } @article {pmid29439244, year = {2018}, author = {Rogge, PC}, title = {My climate change crisis.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {706}, doi = {10.1126/science.359.6376.706}, pmid = {29439244}, issn = {1095-9203}, } @article {pmid29439243, year = {2018}, author = {Hughes, MP and Sawaya, MR and Boyer, DR and Goldschmidt, L and Rodriguez, JA and Cascio, D and Chong, L and Gonen, T and Eisenberg, DS}, title = {Atomic structures of low-complexity protein segments reveal kinked β sheets that assemble networks.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {698-701}, pmid = {29439243}, issn = {1095-9203}, support = {//Howard Hughes Medical Institute/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; RF1 AG054022/AG/NIA NIH HHS/United States ; T32 GM007185/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Protein Conformation, beta-Strand ; *Protein Interaction Domains and Motifs ; Proteome/chemistry ; }, abstract = {Subcellular membraneless assemblies are a reinvigorated area of study in biology, with spirited scientific discussions on the forces between the low-complexity protein domains within these assemblies. To illuminate these forces, we determined the atomic structures of five segments from protein low-complexity domains associated with membraneless assemblies. Their common structural feature is the stacking of segments into kinked β sheets that pair into protofilaments. Unlike steric zippers of amyloid fibrils, the kinked sheets interact weakly through polar atoms and aromatic side chains. By computationally threading the human proteome on our kinked structures, we identified hundreds of low-complexity segments potentially capable of forming such interactions. These segments are found in proteins as diverse as RNA binders, nuclear pore proteins, and keratins, which are known to form networks and localize to membraneless assemblies.}, } @article {pmid29439242, year = {2018}, author = {Gandal, MJ and Haney, JR and Parikshak, NN and Leppa, V and Ramaswami, G and Hartl, C and Schork, AJ and Appadurai, V and Buil, A and Werge, TM and Liu, C and White, KP and , and , and , and Horvath, S and Geschwind, DH}, title = {Shared molecular neuropathology across major psychiatric disorders parallels polygenic overlap.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {693-697}, pmid = {29439242}, issn = {1095-9203}, support = {P50 MH096891/MH/NIMH NIH HHS/United States ; R01 MH094714/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; P50 MH106438/MH/NIMH NIH HHS/United States ; R21 MH103877/MH/NIMH NIH HHS/United States ; U01 MH103365/MH/NIMH NIH HHS/United States ; R01 MH075916/MH/NIMH NIH HHS/United States ; R01 MH100027/MH/NIMH NIH HHS/United States ; P50 MH084051/MH/NIMH NIH HHS/United States ; R01 MH110927/MH/NIMH NIH HHS/United States ; F31 AG051381/AG/NIA NIH HHS/United States ; U01 MH103392/MH/NIMH NIH HHS/United States ; U01 MH103346/MH/NIMH NIH HHS/United States ; R01 MH105472/MH/NIMH NIH HHS/United States ; U01 MH103340/MH/NIMH NIH HHS/United States ; R01 MH103340/MH/NIMH NIH HHS/United States ; P50 MH084053/MH/NIMH NIH HHS/United States ; U01 MH103339/MH/NIMH NIH HHS/United States ; R01 MH097276/MH/NIMH NIH HHS/United States ; R03 AG022193/AG/NIA NIH HHS/United States ; P01 AG002219/AG/NIA NIH HHS/United States ; R01 MH110920/MH/NIMH NIH HHS/United States ; R01 MH093725/MH/NIMH NIH HHS/United States ; P50 AG005138/AG/NIA NIH HHS/United States ; P50 MH096890/MH/NIMH NIH HHS/United States ; R01 ES024988/ES/NIEHS NIH HHS/United States ; R21 MH102791/MH/NIMH NIH HHS/United States ; R01 MH105898/MH/NIMH NIH HHS/United States ; R21 MH105881/MH/NIMH NIH HHS/United States ; HHSN271201300031C/MH/NIMH NIH HHS/United States ; P50 MH066392/MH/NIMH NIH HHS/United States ; R01 MH109912/MH/NIMH NIH HHS/United States ; R01 MH080405/MH/NIMH NIH HHS/United States ; R03 MH066923/MH/NIMH NIH HHS/United States ; R01 MH085542/MH/NIMH NIH HHS/United States ; U01 MH116492/MH/NIMH NIH HHS/United States ; P50 MH106934/MH/NIMH NIH HHS/United States ; }, mesh = {Cerebral Cortex/metabolism ; Gene Expression Profiling ; Gene Expression Regulation ; *Genetic Predisposition to Disease ; Humans ; Mental Disorders/*genetics ; *Multifactorial Inheritance ; Nervous System Diseases/*genetics ; Polymorphism, Single Nucleotide ; Transcription, Genetic ; }, abstract = {The predisposition to neuropsychiatric disease involves a complex, polygenic, and pleiotropic genetic architecture. However, little is known about how genetic variants impart brain dysfunction or pathology. We used transcriptomic profiling as a quantitative readout of molecular brain-based phenotypes across five major psychiatric disorders-autism, schizophrenia, bipolar disorder, depression, and alcoholism-compared with matched controls. We identified patterns of shared and distinct gene-expression perturbations across these conditions. The degree of sharing of transcriptional dysregulation is related to polygenic (single-nucleotide polymorphism-based) overlap across disorders, suggesting a substantial causal genetic component. This comprehensive systems-level view of the neurobiological architecture of major neuropsychiatric illness demonstrates pathways of molecular convergence and specificity.}, } @article {pmid29439241, year = {2018}, author = {Chen, S and Weitemier, AZ and Zeng, X and He, L and Wang, X and Tao, Y and Huang, AJY and Hashimotodani, Y and Kano, M and Iwasaki, H and Parajuli, LK and Okabe, S and Teh, DBL and All, AH and Tsutsui-Kimura, I and Tanaka, KF and Liu, X and McHugh, TJ}, title = {Near-infrared deep brain stimulation via upconversion nanoparticle-mediated optogenetics.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {679-684}, doi = {10.1126/science.aaq1144}, pmid = {29439241}, issn = {1095-9203}, mesh = {Animals ; Brain/*physiology ; Deep Brain Stimulation/*methods ; Light ; Mice ; Mice, Transgenic ; *Nanoparticles ; Neurons/*physiology ; Optogenetics/*methods ; }, abstract = {Optogenetics has revolutionized the experimental interrogation of neural circuits and holds promise for the treatment of neurological disorders. It is limited, however, because visible light cannot penetrate deep inside brain tissue. Upconversion nanoparticles (UCNPs) absorb tissue-penetrating near-infrared (NIR) light and emit wavelength-specific visible light. Here, we demonstrate that molecularly tailored UCNPs can serve as optogenetic actuators of transcranial NIR light to stimulate deep brain neurons. Transcranial NIR UCNP-mediated optogenetics evoked dopamine release from genetically tagged neurons in the ventral tegmental area, induced brain oscillations through activation of inhibitory neurons in the medial septum, silenced seizure by inhibition of hippocampal excitatory cells, and triggered memory recall. UCNP technology will enable less-invasive optical neuronal activity manipulation with the potential for remote therapy.}, } @article {pmid29439240, year = {2018}, author = {Vampa, G and Hammond, TJ and Nesrallah, M and Naumov, AY and Corkum, PB and Brabec, T}, title = {Light amplification by seeded Kerr instability.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {673-675}, doi = {10.1126/science.aaq0053}, pmid = {29439240}, issn = {1095-9203}, abstract = {Amplification of femtosecond laser pulses typically requires a lasing medium or a nonlinear crystal. In either case, the chemical properties of the lasing medium or the momentum conservation in the nonlinear crystal constrain the frequency and the bandwidth of the amplified pulses. We demonstrate high gain amplification (greater than 1000) of widely tunable (0.5 to 2.2 micrometers) and short (less than 60 femtosecond) laser pulses, up to intensities of 1 terawatt per square centimeter, by seeding the modulation instability in an Y3Al5O12 crystal pumped by femtosecond near-infrared pulses. Our method avoids constraints related to doping and phase matching and therefore can occur in a wider pool of glasses and crystals even at far-infrared frequencies and for single-cycle pulses. Such amplified pulses are ideal to study strong-field processes in solids and highly excited states in gases.}, } @article {pmid29439239, year = {2018}, author = {Barik, S and Karasahin, A and Flower, C and Cai, T and Miyake, H and DeGottardi, W and Hafezi, M and Waks, E}, title = {A topological quantum optics interface.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {666-668}, doi = {10.1126/science.aaq0327}, pmid = {29439239}, issn = {1095-9203}, abstract = {The application of topology in optics has led to a new paradigm in developing photonic devices with robust properties against disorder. Although considerable progress on topological phenomena has been achieved in the classical domain, the realization of strong light-matter coupling in the quantum domain remains unexplored. We demonstrate a strong interface between single quantum emitters and topological photonic states. Our approach creates robust counterpropagating edge states at the boundary of two distinct topological photonic crystals. We demonstrate the chiral emission of a quantum emitter into these modes and establish their robustness against sharp bends. This approach may enable the development of quantum optics devices with built-in protection, with potential applications in quantum simulation and sensing.}, } @article {pmid29439238, year = {2018}, author = {Pilz, GA and Bottes, S and Betizeau, M and Jörg, DJ and Carta, S and Simons, BD and Helmchen, F and Jessberger, S}, title = {Live imaging of neurogenesis in the adult mouse hippocampus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {658-662}, doi = {10.1126/science.aao5056}, pmid = {29439238}, issn = {1095-9203}, support = {//European Research Council/International ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics ; Cell Death ; *Cell Division/genetics ; Hippocampus/*cytology/*growth & development ; Mice ; Nerve Net/cytology/growth & development ; Neural Stem Cells/*cytology ; *Neurogenesis/genetics ; Neuroglia/cytology ; *Neuroimaging ; Neurons/*cytology ; Promoter Regions, Genetic ; }, abstract = {Neural stem and progenitor cells (NSPCs) generate neurons throughout life in the mammalian hippocampus. We used chronic in vivo imaging and followed genetically labeled individual NSPCs and their progeny in the mouse hippocampus for up to 2 months. We show that NSPCs targeted by the endogenous Achaete-scute homolog 1 (Ascl1) promoter undergo limited rounds of symmetric and asymmetric divisions, eliciting a burst of neurogenic activity, after which they are lost. Further, our data reveal unexpected asymmetric divisions of nonradial glia-like NSPCs. Cell fates of Ascl1-labeled lineages suggest a developmental-like program involving a sequential transition from a proliferative to a neurogenic phase. By providing a comprehensive description of lineage relationships, from dividing NSPCs to newborn neurons integrating into the hippocampal circuitry, our data offer insight into how NSPCs support life-long hippocampal neurogenesis.}, } @article {pmid29439237, year = {2018}, author = {Dakin, R and Segre, PS and Straw, AD and Altshuler, DL}, title = {Morphology, muscle capacity, skill, and maneuvering ability in hummingbirds.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {653-657}, doi = {10.1126/science.aao7104}, pmid = {29439237}, issn = {1095-9203}, mesh = {Acceleration ; Animals ; Biological Evolution ; Birds/*anatomy & histology/classification/*physiology ; Flight, Animal/*physiology ; Muscle, Skeletal/*anatomy & histology/*physiology ; Phylogeny ; Rotation ; South America ; Wings, Animal/*anatomy & histology/*physiology ; }, abstract = {How does agility evolve? This question is challenging because natural movement has many degrees of freedom and can be influenced by multiple traits. We used computer vision to record thousands of translations, rotations, and turns from more than 200 hummingbirds from 25 species, revealing that distinct performance metrics are correlated and that species diverge in their maneuvering style. Our analysis demonstrates that the enhanced maneuverability of larger species is explained by their proportionately greater muscle capacity and lower wing loading. Fast acceleration maneuvers evolve by recruiting changes in muscle capacity, whereas fast rotations and sharp turns evolve by recruiting changes in wing morphology. Both species and individuals use turns that play to their strengths. These results demonstrate how both skill and biomechanical traits shape maneuvering behavior.}, } @article {pmid29439236, year = {2018}, author = {Yang, H and Ma, M and Thompson, JR and Flower, RJ}, title = {Transport expansion threatens the Arctic.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {646-647}, doi = {10.1126/science.aar5443}, pmid = {29439236}, issn = {1095-9203}, mesh = {Arctic Regions ; *Environmental Monitoring ; Humans ; }, } @article {pmid29439235, year = {2018}, author = {Konarzewski, M and Zabielski, R and Kowalczyk, R and Duszyński, J}, title = {Białowieża Forest: Logging data lacking.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {646}, doi = {10.1126/science.aat0295}, pmid = {29439235}, issn = {1095-9203}, mesh = {*Forestry ; *Forests ; Humans ; Trees ; }, } @article {pmid29439234, year = {2018}, author = {Blicharska, M and Smithers, RJ}, title = {Białowieża Forest: Political stands.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {646}, doi = {10.1126/science.aar7173}, pmid = {29439234}, issn = {1095-9203}, mesh = {*Forests ; *Trees ; }, } @article {pmid29439233, year = {2018}, author = {Serwadda, D and Ndebele, P and Grabowski, MK and Bajunirwe, F and Wanyenze, RK}, title = {Open data sharing and the Global South-Who benefits?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {642-643}, doi = {10.1126/science.aap8395}, pmid = {29439233}, issn = {1095-9203}, } @article {pmid29439232, year = {2018}, author = {Meschede, D}, title = {Superradiators created atom by atom.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {641}, doi = {10.1126/science.aas9067}, pmid = {29439232}, issn = {1095-9203}, } @article {pmid29439231, year = {2018}, author = {Götz, M}, title = {Revising concepts about adult stem cells.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {639-640}, doi = {10.1126/science.aar7732}, pmid = {29439231}, issn = {1095-9203}, mesh = {Adult ; *Adult Stem Cells ; Humans ; }, } @article {pmid29439230, year = {2018}, author = {Amo, A}, title = {When quantum optics meets topology.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {638-639}, doi = {10.1126/science.aar7396}, pmid = {29439230}, issn = {1095-9203}, mesh = {*Optics and Photonics ; *Quantum Theory ; }, } @article {pmid29439229, year = {2018}, author = {Wainwright, PC}, title = {How hummingbirds stay nimble on the wing.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {636-637}, doi = {10.1126/science.aar7615}, pmid = {29439229}, issn = {1095-9203}, mesh = {Animals ; Biomechanical Phenomena ; *Birds ; *Flight, Animal ; Wings, Animal ; }, } @article {pmid29439228, year = {2018}, author = {Chen, Y and Popko, B}, title = {Cholesterol crystals impede nerve repair.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {635-636}, doi = {10.1126/science.aar7369}, pmid = {29439228}, issn = {1095-9203}, support = {R01 NS034939/NS/NINDS NIH HHS/United States ; R01 NS099334/NS/NINDS NIH HHS/United States ; }, mesh = {Cholesterol/*chemistry ; *Crystallization ; Humans ; *Nerve Regeneration ; }, } @article {pmid29439227, year = {2018}, author = {Feliu, N and Neher, E and Parak, WJ}, title = {Toward an optically controlled brain.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {633-634}, doi = {10.1126/science.aar7379}, pmid = {29439227}, issn = {1095-9203}, mesh = {*Brain ; Humans ; }, } @article {pmid29439226, year = {2018}, author = {Gligorovski, S and Abbatt, JPD}, title = {An indoor chemical cocktail.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {632-633}, doi = {10.1126/science.aar6837}, pmid = {29439226}, issn = {1095-9203}, mesh = {Air Pollutants/*chemistry ; *Air Pollution, Indoor ; *Health ; Humans ; }, } @article {pmid29439225, year = {2018}, author = {Larson, C}, title = {China's AI imperative.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {628-630}, doi = {10.1126/science.359.6376.628}, pmid = {29439225}, issn = {1095-9203}, } @article {pmid29439224, year = {2018}, author = {Grimm, D}, title = {The happiness project.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {624-627}, doi = {10.1126/science.359.6376.624}, pmid = {29439224}, issn = {1095-9203}, mesh = {*Animal Experimentation ; Animal Welfare/*standards ; Animals ; *Animals, Laboratory ; Fishes ; Mice ; Rats ; }, } @article {pmid29439223, year = {2018}, author = {Reese, A}, title = {As polar ozone mends, UV shield closer to equator thins.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {623}, doi = {10.1126/science.359.6376.623}, pmid = {29439223}, issn = {1095-9203}, } @article {pmid29439222, year = {2018}, author = {Enserink, M}, title = {Tobacco giant's research largesse ignites controversy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {622-623}, doi = {10.1126/science.359.6376.622}, pmid = {29439222}, issn = {1095-9203}, mesh = {*Electronic Nicotine Delivery Systems ; *Financing, Organized ; *Harm Reduction ; Humans ; Netherlands ; Research/economics ; Tobacco/*adverse effects ; Tobacco Industry/*economics ; }, } @article {pmid29439221, year = {2018}, author = {Kaiser, J}, title = {Gene therapy field hit by fresh safety concern.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {621}, doi = {10.1126/science.359.6376.621}, pmid = {29439221}, issn = {1095-9203}, mesh = {Animal Experimentation ; Animals ; Clinical Trials as Topic ; *Dependovirus ; Genetic Therapy/*adverse effects ; Haplorhini ; Humans ; Spinal Muscular Atrophies of Childhood/*therapy ; Survival of Motor Neuron 1 Protein/*genetics ; Swine ; }, } @article {pmid29439220, year = {2018}, author = {Kupferschmidt, K}, title = {Use of cholera vaccines expands, raising hopes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {620-621}, doi = {10.1126/science.359.6376.620}, pmid = {29439220}, issn = {1095-9203}, mesh = {Cholera/*prevention & control ; Cholera Vaccines/*supply & distribution/*therapeutic use ; Disease Outbreaks/*prevention & control ; Humans ; Vaccination ; World Health Organization ; }, } @article {pmid29439219, year = {2018}, author = {Dengler, R}, title = {Psychiatrists begin to map genetic architecture of mental disorders.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {619}, doi = {10.1126/science.359.6376.619}, pmid = {29439219}, issn = {1095-9203}, mesh = {Brain/*metabolism ; *Chromosome Mapping ; Diagnostic Tests, Routine ; Gene Expression ; Humans ; Mental Disorders/diagnosis/*genetics/therapy ; Psychiatry ; }, } @article {pmid29439218, year = {2018}, author = {Service, RF}, title = {China's planned exascale computer threatens Summit's position at the top.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {618}, doi = {10.1126/science.359.6376.618}, pmid = {29439218}, issn = {1095-9203}, } @article {pmid29439217, year = {2018}, author = {Service, RF}, title = {Design for U.S. exascale computer takes shape.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {617-618}, doi = {10.1126/science.359.6376.617}, pmid = {29439217}, issn = {1095-9203}, } @article {pmid29439216, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {614-616}, doi = {10.1126/science.359.6376.614}, pmid = {29439216}, issn = {1095-9203}, } @article {pmid29439215, year = {2018}, author = {Colglazier, EW}, title = {War and peace in the nuclear age.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {613}, doi = {10.1126/science.aat0593}, pmid = {29439215}, issn = {1095-9203}, } @article {pmid29439214, year = {2018}, author = {Kitada, T and DiAndreth, B and Teague, B and Weiss, R}, title = {Programming gene and engineered-cell therapies with synthetic biology.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {}, doi = {10.1126/science.aad1067}, pmid = {29439214}, issn = {1095-9203}, mesh = {Cell Engineering/*methods ; *Cell- and Tissue-Based Therapy ; *Cellular Reprogramming Techniques ; DNA/genetics ; Gene Expression ; Gene Regulatory Networks ; Genes, Synthetic ; Genetic Engineering/*methods ; *Genetic Therapy ; Humans ; RNA/genetics ; Recombinant Fusion Proteins ; Synthetic Biology/*methods ; Transgenes ; }, abstract = {Gene and engineered-cell therapies promise to treat diseases by genetically modifying cells to carry out therapeutic tasks. Although the field has had some success in treating monogenic disorders and hematological malignancies, current approaches are limited to overexpression of one or a few transgenes, constraining the diseases that can be treated with this approach and leading to potential concerns over safety and efficacy. Synthetic gene networks can regulate the dosage, timing, and localization of gene expression and therapeutic activity in response to small molecules and disease biomarkers. Such "programmable" gene and engineered-cell therapies will provide new interventions for incurable or difficult-to-treat diseases.}, } @article {pmid29439204, year = {2018}, author = {Di Modugno, F and Caprara, V and Chellini, L and Tocci, P and Spadaro, F and Ferrandina, G and Sacconi, A and Blandino, G and Nisticò, P and Bagnato, A and Rosanò, L}, title = {hMENA is a key regulator in endothelin-1/β-arrestin1-induced invadopodial function and metastatic process.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3132-3137}, pmid = {29439204}, issn = {1091-6490}, mesh = {Animals ; Cystadenocarcinoma, Serous/genetics/mortality/*pathology ; Cytoskeleton/metabolism ; Endothelin A Receptor Antagonists/pharmacology ; Endothelin-1/*metabolism ; Female ; Gene Expression Regulation, Neoplastic ; Humans ; Mice, Nude ; Microfilament Proteins/genetics/*metabolism ; Ovarian Neoplasms/genetics/mortality/*pathology ; Podosomes/drug effects/metabolism ; Pyrimidines/pharmacology ; Receptor, Endothelin A/metabolism ; Sulfonamides/pharmacology ; Xenograft Model Antitumor Assays ; beta-Arrestin 1/*metabolism ; rhoC GTP-Binding Protein/metabolism ; }, abstract = {Aberrant activation of endothelin-1 receptors (ET-1R) elicits pleiotropic effects relevant for tumor progression. The network activated by this receptor might be finely, spatially, and temporarily orchestrated by β-arrestin1 (β-arr1)-driven interactome. Here, we identify hMENA, a member of the actin-regulatory protein ENA/VASP family, as an interacting partner of β-arr1, necessary for invadopodial function downstream of ET-1R in serous ovarian cancer (SOC) progression. ET-1R activation by ET-1 up-regulates expression of hMENA/hMENAΔv6 isoforms through β-arr1, restricted to mesenchymal-like invasive SOC cells. The interaction of β-arr1 with hMENA/hMENAΔv6 triggered by ET-1 leads to activation of RhoC and cortactin, recruitment of membrane type 1-matrix metalloprotease, and invadopodia maturation, thereby enhancing cell plasticity, transendothelial migration, and the resulting spread of invasive cells. The treatment with the ET-1R antagonist macitentan impairs the interaction of β-arr1 with hMENA and inhibits invadopodial maturation and tumor dissemination in SOC orthotopic xenografts. Finally, high ETAR/hMENA/β-arr1 gene expression signature is associated with a poor prognosis in SOC patients. These data define a pivotal function of hMENA/hMENAΔv6 for ET-1/β-arr1-induced invadopodial activity and ovarian cancer progression.}, } @article {pmid29439203, year = {2018}, author = {Mori, T and Cahn, JKB and Wilson, MC and Meoded, RA and Wiebach, V and Martinez, AFC and Helfrich, EJN and Albersmeier, A and Wibberg, D and Dätwyler, S and Keren, R and Lavy, A and Rückert, C and Ilan, M and Kalinowski, J and Matsunaga, S and Takeyama, H and Piel, J}, title = {Single-bacterial genomics validates rich and varied specialized metabolism of uncultivated Entotheonella sponge symbionts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1718-1723}, pmid = {29439203}, issn = {1091-6490}, mesh = {Animals ; Bacteria/chemistry/genetics/isolation & purification ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics/metabolism ; Genome, Bacterial ; Genomics ; Polyketides/metabolism ; *Symbiosis ; Theonella/chemistry/*microbiology/physiology ; }, abstract = {Marine sponges are prolific sources of unique bioactive natural products. The sponge Theonella swinhoei is represented by several distinct variants with largely nonoverlapping chemistry. For the Japanese chemotype Y harboring diverse complex polyketides and peptides, we previously provided genomic and functional evidence that a single symbiont, the filamentous, multicellular organism "Candidatus Entotheonella factor," produces almost all of these compounds. To obtain further insights into the chemistry of "Entotheonella," we investigated another phylotype, "Candidatus Entotheonella serta," present in the T. swinhoei WA sponge chemotype, a source of theonellamide- and misakinolide-type compounds. Unexpectedly, considering the lower chemical diversity, sequencing of individual bacterial filaments revealed an even larger number of biosynthetic gene regions than for Ca E. factor, with virtually no overlap. These included genes for misakinolide and theonellamide biosynthesis, the latter assigned by comparative genomic and metabolic analysis of a T. swinhoei chemotype from Israel, and by biochemical studies. The data suggest that both compound families, which were among the earliest model substances to study bacterial producers in sponges, originate from the same bacterium in T. swinhoei WA. They also add evidence that metabolic richness and variability could be a more general feature of Entotheonella symbionts.}, } @article {pmid29439202, year = {2018}, author = {Moglie, MJ and Fuchs, PA and Elgoyhen, AB and Goutman, JD}, title = {Compartmentalization of antagonistic Ca2+ signals in developing cochlear hair cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2095-E2104}, pmid = {29439202}, issn = {1091-6490}, support = {P30 DC005211/DC/NIDCD NIH HHS/United States ; R01 DC001508/DC/NIDCD NIH HHS/United States ; R01 DC015309/DC/NIDCD NIH HHS/United States ; R03 TW009403/TW/FIC NIH HHS/United States ; }, mesh = {Acetylcholine/pharmacology ; Action Potentials ; Animals ; Auditory Pathways/physiology ; Calcium/*metabolism ; *Calcium Signaling ; Cochlea/*physiology ; Electric Stimulation ; Female ; Glutamic Acid/metabolism ; Hair Cells, Auditory, Inner/*cytology ; Hearing ; Male ; Mice ; Neurons/physiology ; Patch-Clamp Techniques ; Potassium Channels, Calcium-Activated/physiology ; Rats ; Rats, Sprague-Dawley ; Receptors, Nicotinic/physiology ; Signal Transduction ; Synapses/*physiology ; }, abstract = {During a critical developmental period, cochlear inner hair cells (IHCs) exhibit sensory-independent activity, featuring action potentials in which Ca2+ ions play a fundamental role in driving both spiking and glutamate release onto synapses with afferent auditory neurons. This spontaneous activity is controlled by a cholinergic input to the IHC, activating a specialized nicotinic receptor with high Ca2+ permeability, and coupled to the activation of hyperpolarizing SK channels. The mechanisms underlying distinct excitatory and inhibitory Ca2+ roles within a small, compact IHC are unknown. Making use of Ca2+ imaging, afferent auditory bouton recordings, and electron microscopy, the present work shows that unusually high intracellular Ca2+ buffering and "subsynaptic" cisterns provide efficient compartmentalization and tight control of cholinergic Ca2+ signals. Thus, synaptic efferent Ca2+ spillover and cross-talk are prevented, and the cholinergic input preserves its inhibitory signature to ensure normal development of the auditory system.}, } @article {pmid29439201, year = {2018}, author = {Shi, R and Tanaka, H}, title = {Impact of local symmetry breaking on the physical properties of tetrahedral liquids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1980-1985}, pmid = {29439201}, issn = {1091-6490}, abstract = {Water and silica are the most important materials with local tetrahedral symmetry. They have similar crystalline polymorphs and exhibit anomalous density maximum in the liquid state. However, water and silica also show very different characteristics. For instance, the density of water varies much more sharply than that of liquid silica near the maximum as temperature changes. More notably, silica is a very good glass-former, but water is an extremely poor one. The physical origins of these similarities and differences still remain elusive, due to the lack of a microscopic understanding of the structural ordering in these two important liquids. Here, by accessing microscopic structural information by computer simulations, we reveal that local translational symmetry breaking is responsible for the density anomalies. On the other hand, the difference in the degree of local orientational symmetry breaking between water and silica, which originates from the difference in their bonding nature, causes not only the difference in the sharpness of density anomalies, but also their distinct glass-forming abilities. Our work not only shows the crucial roles of local translational and orientational symmetry breaking in the physical properties of the two extremely important materials, water and silica, but also provides a unified scenario applicable for other tetrahedral liquids such as Si, Ge, C, BeF2, and GeO2.}, } @article {pmid29439200, year = {2018}, author = {Terry, SJ and Donà, F and Osenberg, P and Carlton, JG and Eggert, US}, title = {Capping protein regulates actin dynamics during cytokinetic midbody maturation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2138-2143}, pmid = {29439200}, issn = {1091-6490}, support = {R01 GM082834/GM/NIGMS NIH HHS/United States ; 110060/Z/15/Z//Wellcome Trust/United Kingdom ; 206346/Z/17/Z//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; 306659//European Research Council/International ; 093603/Z/10/Z//Wellcome Trust/United Kingdom ; }, mesh = {Actin Capping Proteins/*physiology ; Actin Cytoskeleton/*physiology ; Actins ; Cell Membrane ; Cytokinesis/*physiology ; Endosomal Sorting Complexes Required for Transport/metabolism ; Epithelial Cells/physiology ; Epithelium, Corneal/cytology ; Fetal Proteins/genetics/metabolism ; Gene Expression Regulation/physiology ; HeLa Cells ; Humans ; Microfilament Proteins ; Nuclear Proteins/genetics/metabolism ; }, abstract = {During cytokinesis, a cleavage furrow generated by actomyosin ring contraction is restructured into the midbody, a platform for the assembly of the abscission machinery that controls the final separation of daughter cells. The polymerization state of F-actin is important during assembly, ingression, disassembly, and closure of the contractile ring and for the cytoskeletal remodeling that accompanies midbody formation and progression to abscission. Actin filaments must be cleared from the abscission sites before the final cut can take place. Although many conserved proteins interact with and influence the polymerization state of actin filaments, it is poorly understood how they regulate cytokinesis in higher eukaryotes. We report here that the actin capping protein (CP), a barbed end actin binding protein, participates in the control of actin polymerization during later stages of cytokinesis in human cells. Cells depleted of CP furrow and form early midbodies, but they fail cytokinesis. Appropriate recruitment of the ESCRT-III abscission machinery to the midbody is impaired, preventing the cell from progressing to the abscission stage. To generate actin filaments of optimal length, different actin nucleators, such as formins, balance CP's activity. Loss of actin capping activity leads to excessive accumulation of formin-based linear actin filaments. Depletion of the formin FHOD1 results in partial rescue of CP-induced cytokinesis failure, suggesting that it can antagonize CP activity during midbody maturation. Our work suggests that the actin cytoskeleton is remodeled in a stepwise manner during cytokinesis, with different regulators at different stages required for successful progression to abscission.}, } @article {pmid29439199, year = {2018}, author = {Wong, MY and Liu, C and Wang, SSH and Roquas, ACF and Fowler, SC and Kaeser, PS}, title = {Liprin-α3 controls vesicle docking and exocytosis at the active zone of hippocampal synapses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2234-2239}, pmid = {29439199}, issn = {1091-6490}, support = {P30 NS072030/NS/NINDS NIH HHS/United States ; R01 NS083898/NS/NINDS NIH HHS/United States ; R01 MH113349/MH/NIMH NIH HHS/United States ; P30 HD018655/HD/NICHD NIH HHS/United States ; U54 HD090255/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Central Nervous System/physiology ; Electrophysiology ; *Exocytosis ; Hippocampus/*physiology ; Mice ; Mice, Knockout ; Microscopy ; Microscopy, Confocal ; Neurons/physiology ; Synapses/*physiology ; Synaptic Transmission/physiology ; Synaptic Vesicles/physiology ; Vesicular Transport Proteins/genetics/*metabolism ; }, abstract = {The presynaptic active zone provides sites for vesicle docking and release at central nervous synapses and is essential for speed and accuracy of synaptic transmission. Liprin-α binds to several active zone proteins, and loss-of-function studies in invertebrates established important roles for Liprin-α in neurodevelopment and active zone assembly. However, Liprin-α localization and functions in vertebrates have remained unclear. We used stimulated emission depletion superresolution microscopy to systematically determine the localization of Liprin-α2 and Liprin-α3, the two predominant Liprin-α proteins in the vertebrate brain, relative to other active-zone proteins. Both proteins were widely distributed in hippocampal nerve terminals, and Liprin-α3, but not Liprin-α2, had a prominent component that colocalized with the active-zone proteins Bassoon, RIM, Munc13, RIM-BP, and ELKS. To assess Liprin-α3 functions, we generated Liprin-α3-KO mice by using CRISPR/Cas9 gene editing. We found reduced synaptic vesicle tethering and docking in hippocampal neurons of Liprin-α3-KO mice, and synaptic vesicle exocytosis was impaired. Liprin-α3 KO also led to mild alterations in active zone structure, accompanied by translocation of Liprin-α2 to active zones. These findings establish important roles for Liprin-α3 in active-zone assembly and function, and suggest that interplay between various Liprin-α proteins controls their active-zone localization.}, } @article {pmid29439198, year = {2018}, author = {Kennedy, AB}, title = {Reported extreme wave heights off Ireland are artifacts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1937-E1938}, pmid = {29439198}, issn = {1091-6490}, } @article {pmid29439197, year = {2018}, author = {Dewey, JF and Ryan, PD}, title = {Reply to Kennedy: Historical evidence supports remarkable breaking wave heights.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1939}, pmid = {29439197}, issn = {1091-6490}, } @article {pmid29439027, year = {2018}, author = {Geeson, MB and Cummins, CC}, title = {Phosphoric acid as a precursor to chemicals traditionally synthesized from white phosphorus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6382}, pages = {1383-1385}, doi = {10.1126/science.aar6620}, pmid = {29439027}, issn = {1095-9203}, abstract = {White phosphorus, generated in the legacy thermal process for phosphate rock upgrading, has long been the key industrial intermediate for the synthesis of phosphorus-containing chemicals, including herbicides, flame-retardants, catalyst ligands, battery electrolytes, pharmaceuticals, and detergents. In contrast, phosphate fertilizers are made on a much larger scale from phosphoric acid, obtained by treating phosphate rock with sulfuric acid. Dehydration of phosphoric acid using sodium chloride gives trimetaphosphate, and here we report that trichlorosilane, primarily used for the production of high-purity silicon, reduces trimetaphosphate to the previously unknown bis(trichlorosilyl)phosphide anion. This anion offers an entry point to value-added organophosphorus chemicals such as primary and secondary alkyl phosphines, and thus to organophosphinates, and can also be used to prepare phosphine gas and the hexafluorophosphate anion, all previously available only downstream from white phosphorus.}, } @article {pmid29439026, year = {2018}, author = {Kim, YH and Marhon, SA and Zhang, Y and Steger, DJ and Won, KJ and Lazar, MA}, title = {Rev-erbα dynamically modulates chromatin looping to control circadian gene transcription.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1274-1277}, pmid = {29439026}, issn = {1095-9203}, support = {R01 DK045586/DK/NIDDK NIH HHS/United States ; F30 DK112507/DK/NIDDK NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; T32 GM007170/GM/NIGMS NIH HHS/United States ; R01 DK106027/DK/NIDDK NIH HHS/United States ; T32 GM008216/GM/NIGMS NIH HHS/United States ; P01 DK049210/DK/NIDDK NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; }, mesh = {Acetylation ; Animals ; Chromatin/chemistry/*metabolism ; Circadian Rhythm/*genetics ; Enhancer Elements, Genetic ; *Gene Expression Regulation ; Histone Deacetylases/metabolism ; Liver/*metabolism ; Male ; Mediator Complex Subunit 1/metabolism ; Mice ; Mice, Knockout ; Nuclear Proteins/metabolism ; Nuclear Receptor Co-Repressor 1/metabolism ; Nuclear Receptor Subfamily 1, Group D, Member 1/genetics/*metabolism ; Promoter Regions, Genetic ; Protein Conformation ; Transcription Factors/metabolism ; *Transcription, Genetic ; }, abstract = {Mammalian physiology exhibits 24-hour cyclicity due to circadian rhythms of gene expression controlled by transcription factors that constitute molecular clocks. Core clock transcription factors bind to the genome at enhancer sequences to regulate circadian gene expression, but not all binding sites are equally functional. We found that in mice, circadian gene expression in the liver is controlled by rhythmic chromatin interactions between enhancers and promoters. Rev-erbα, a core repressive transcription factor of the clock, opposes functional loop formation between Rev-erbα-regulated enhancers and circadian target gene promoters by recruitment of the NCoR-HDAC3 co-repressor complex, histone deacetylation, and eviction of the elongation factor BRD4 and the looping factor MED1. Thus, a repressive arm of the molecular clock operates by rhythmically modulating chromatin loops to control circadian gene transcription.}, } @article {pmid29439025, year = {2018}, author = {Tan, CSH and Go, KD and Bisteau, X and Dai, L and Yong, CH and Prabhu, N and Ozturk, MB and Lim, YT and Sreekumar, L and Lengqvist, J and Tergaonkar, V and Kaldis, P and Sobota, RM and Nordlund, P}, title = {Thermal proximity coaggregation for system-wide profiling of protein complex dynamics in cells.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1170-1177}, doi = {10.1126/science.aan0346}, pmid = {29439025}, issn = {1095-9203}, mesh = {Cell Line ; Cells ; Chromatin/metabolism ; Hot Temperature ; Humans ; Multiprotein Complexes/*metabolism ; *Protein Aggregates ; Protein Aggregation, Pathological/*metabolism ; Protein Array Analysis ; Protein Biosynthesis ; Protein Folding ; Proteome ; }, abstract = {Proteins differentially interact with each other across cellular states and conditions, but an efficient proteome-wide strategy to monitor them is lacking. We report the application of thermal proximity coaggregation (TPCA) for high-throughput intracellular monitoring of protein complex dynamics. Significant TPCA signatures observed among well-validated protein-protein interactions correlate positively with interaction stoichiometry and are statistically observable in more than 350 annotated human protein complexes. Using TPCA, we identified many complexes without detectable differential protein expression, including chromatin-associated complexes, modulated in S phase of the cell cycle. Comparison of six cell lines by TPCA revealed cell-specific interactions even in fundamental cellular processes. TPCA constitutes an approach for system-wide studies of protein complexes in nonengineered cells and tissues and might be used to identify protein complexes that are modulated in diseases.}, } @article {pmid29439024, year = {2018}, author = {Mure, LS and Le, HD and Benegiamo, G and Chang, MW and Rios, L and Jillani, N and Ngotho, M and Kariuki, T and Dkhissi-Benyahya, O and Cooper, HM and Panda, S}, title = {Diurnal transcriptome atlas of a primate across major neural and peripheral tissues.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {}, pmid = {29439024}, issn = {1095-9203}, support = {P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Brain/metabolism/*physiology ; Circadian Clocks/*genetics ; Circadian Rhythm/*genetics ; Genomics ; Male ; Papio anubis/*genetics/*physiology ; *Transcriptome ; }, abstract = {Diurnal gene expression patterns underlie time-of-the-day-specific functional specialization of tissues. However, available circadian gene expression atlases of a few organs are largely from nocturnal vertebrates. We report the diurnal transcriptome of 64 tissues, including 22 brain regions, sampled every 2 hours over 24 hours, from the primate Papio anubis (baboon). Genomic transcription was highly rhythmic, with up to 81.7% of protein-coding genes showing daily rhythms in expression. In addition to tissue-specific gene expression, the rhythmic transcriptome imparts another layer of functional specialization. Most ubiquitously expressed genes that participate in essential cellular functions exhibit rhythmic expression in a tissue-specific manner. The peak phases of rhythmic gene expression clustered around dawn and dusk, with a "quiescent period" during early night. Our findings also unveil a different temporal organization of central and peripheral tissues between diurnal and nocturnal animals.}, } @article {pmid29439023, year = {2018}, author = {Norimoto, H and Makino, K and Gao, M and Shikano, Y and Okamoto, K and Ishikawa, T and Sasaki, T and Hioki, H and Fujisawa, S and Ikegaya, Y}, title = {Hippocampal ripples down-regulate synapses.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6383}, pages = {1524-1527}, doi = {10.1126/science.aao0702}, pmid = {29439023}, issn = {1095-9203}, mesh = {Animals ; Down-Regulation ; Hippocampus/*physiology ; Learning/physiology ; Long-Term Synaptic Depression/*physiology ; Memory/*physiology ; Mice ; Mice, Inbred C57BL ; Receptors, N-Methyl-D-Aspartate/genetics/physiology ; Sleep/physiology ; Synapses/*physiology ; }, abstract = {The specific effects of sleep on synaptic plasticity remain unclear. We report that mouse hippocampal sharp-wave ripple oscillations serve as intrinsic events that trigger long-lasting synaptic depression. Silencing of sharp-wave ripples during slow-wave states prevented the spontaneous down-regulation of net synaptic weights and impaired the learning of new memories. The synaptic down-regulation was dependent on the N-methyl-d-aspartate receptor and selective for a specific input pathway. Thus, our findings are consistent with the role of slow-wave states in refining memory engrams by reducing recent memory-irrelevant neuronal activity and suggest a previously unrecognized function for sharp-wave ripples.}, } @article {pmid29438507, year = {2018}, author = {Peralta-Sánchez, JM and Martín-Platero, AM and Wegener-Parfrey, L and Martínez-Bueno, M and Rodríguez-Ruano, S and Navas-Molina, JA and Vázquez-Baeza, Y and Martín-Gálvez, D and Martín-Vivaldi, M and Ibáñez-Álamo, JD and Knight, R and Soler, JJ}, title = {Bacterial density rather than diversity correlates with hatching success across different avian species.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy022}, pmid = {29438507}, issn = {1574-6941}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Bacterial communities within avian nests are considered an important determinant of egg viability, potentially selecting for traits that confer embryos with protection against trans-shell infection. A high bacterial density on the eggshell increases hatching failure, whether this effect could be due to changes in bacterial community or just a general increase in bacterial density. We explored this idea using intra- and interspecific comparisons of the relationship between hatching success and eggshell bacteria characterized by culture and molecular techniques (fingerprinting and high-throughput sequencing). We collected information for 152 nests belonging to 17 bird species. Hatching failures occurred more frequently in nests with higher density of aerobic mesophilic bacteria on their eggshells. Bacterial community was also related to hatching success, but only when minority bacterial operational taxonomic units were considered. These findings support the hypothesis that bacterial density is a selective agent of embryo viability, and hence a proxy of hatching failure only within species. Although different avian species hold different bacterial densities or assemblages on their eggs, the association between bacteria and hatching success was similar for different species. This result suggests that interspecific differences in antibacterial defenses are responsible for keeping the hatching success at similar levels in different species.}, } @article {pmid29438502, year = {2018}, author = {Dias, LM and Folador, ARC and Oliveira, AM and Ramos, RTJ and Silva, A and Baraúna, RA}, title = {Genomic Architecture of the Two Cold-Adapted Genera Exiguobacterium and Psychrobacter: Evidence of Functional Reduction in the Exiguobacterium antarcticum B7 Genome.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {731-741}, pmid = {29438502}, issn = {1759-6653}, mesh = {Adaptation, Physiological/*genetics ; Bacillales/*genetics ; Cold Temperature ; Genome, Bacterial/*genetics ; Phylogeny ; Psychrobacter/*genetics ; Sequence Analysis, DNA ; }, abstract = {Exiguobacterium and Psychrobacter are bacterial genera with several cold-adapted species. These extremophiles are commonly isolated from the same habitats in Earth's cryosphere and have great ecological and biotechnological relevance. Thus, through comparative genomic analyses, it was possible to understand the functional diversity of these psychrotrophic and psychrophilic species and present new insights into the microbial adaptation to cold. The nucleotide identity between Exiguobacterium genomes was >90%. Three genomic islands were identified in the E. antarcticum B7 genome. These islands contained genes involved in flagella biosynthesis and chemotaxis, as well as enzymes for carotenoid biosynthesis. Clustering of cold shock proteins by Ka/Ks ratio suggests the occurrence of a positive selection over these genes. Neighbor-joining clustering of complete genomes showed that the E. sibiricum was the most closely related to E. antarcticum. A total of 92 genes were shared between Exiguobacterium and Psychrobacter. A reduction in the genomic content of E. antarcticum B7 was observed. It presented the smallest genome size of its genus and a lower number of genes because of the loss of many gene families compared with the other genomes. In our study, eight genomes of Exiguobacterium and Psychrobacter were compared and analysed. Psychrobacter showed higher genomic plasticity and E. antarcticum B7 presented a large decrease in genomic content without changing its ability to grow in cold environments.}, } @article {pmid29437980, year = {2018}, author = {Ghazizadeh, A and Griggs, W and Leopold, DA and Hikosaka, O}, title = {Temporal-prefrontal cortical network for discrimination of valuable objects in long-term memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E2135-E2144}, pmid = {29437980}, issn = {1091-6490}, mesh = {Animals ; Basal Ganglia/physiology ; Behavior, Animal ; Brain Mapping ; Female ; Fractals ; Hippocampus/physiology ; Macaca ; Magnetic Resonance Imaging ; Male ; *Memory, Long-Term ; Mental Recall/physiology ; Neural Pathways/physiology ; Prefrontal Cortex/*physiology ; Reward ; Temporal Lobe/*physiology ; }, abstract = {Remembering and discriminating objects based on their previously learned values are essential for goal-directed behaviors. While the cerebral cortex is known to contribute to object recognition, surprisingly little is known about its role in retaining long-term object-value associations. To address this question, we trained macaques to arbitrarily associate small or large rewards with many random fractal objects (>100) and then used fMRI to study the long-term retention of value-based response selectivity across the brain. We found a pronounced long-term value memory in core subregions of temporal and prefrontal cortex where, several months after training, fractals previously associated with high reward ("good" stimuli) elicited elevated fMRI responses compared with those associated with low reward ("bad" stimuli). Similar long-term value-based modulation was also observed in subregions of the striatum, amygdala, and claustrum, but not in the hippocampus. The value-modulated temporal-prefrontal subregions showed strong resting-state functional connectivity to each other. Moreover, for areas outside this core, the magnitude of long-term value responses was predicted by the strength of resting-state functional connectivity to the core subregions. In separate testing, free-viewing gaze behavior indicated that the monkeys retained stable long-term memory of object value. These results suggest an implicit and high-capacity memory mechanism in the temporal-prefrontal circuitry and its associated subcortical regions for long-term retention of object-value memories that can guide value-oriented behavior.}, } @article {pmid29437957, year = {2018}, author = {Clarke, LE and Liddelow, SA and Chakraborty, C and Münch, AE and Heiman, M and Barres, BA}, title = {Normal aging induces A1-like astrocyte reactivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1896-E1905}, pmid = {29437957}, issn = {1091-6490}, support = {R01 AG048814/AG/NIA NIH HHS/United States ; }, mesh = {Aging/genetics/*metabolism/psychology ; Animals ; Astrocytes/*metabolism ; Cognition ; Female ; Gene Expression Profiling ; Hippocampus/cytology/metabolism ; Humans ; Interleukin-1alpha/genetics/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Microglia/metabolism ; Neurons/metabolism ; RNA/genetics/metabolism ; Tumor Necrosis Factor-alpha/genetics/metabolism ; }, abstract = {The decline of cognitive function occurs with aging, but the mechanisms responsible are unknown. Astrocytes instruct the formation, maturation, and elimination of synapses, and impairment of these functions has been implicated in many diseases. These findings raise the question of whether astrocyte dysfunction could contribute to cognitive decline in aging. We used the Bac-Trap method to perform RNA sequencing of astrocytes from different brain regions across the lifespan of the mouse. We found that astrocytes have region-specific transcriptional identities that change with age in a region-dependent manner. We validated our findings using fluorescence in situ hybridization and quantitative PCR. Detailed analysis of the differentially expressed genes in aging revealed that aged astrocytes take on a reactive phenotype of neuroinflammatory A1-like reactive astrocytes. Hippocampal and striatal astrocytes up-regulated a greater number of reactive astrocyte genes compared with cortical astrocytes. Moreover, aged brains formed many more A1 reactive astrocytes in response to the neuroinflammation inducer lipopolysaccharide. We found that the aging-induced up-regulation of reactive astrocyte genes was significantly reduced in mice lacking the microglial-secreted cytokines (IL-1α, TNF, and C1q) known to induce A1 reactive astrocyte formation, indicating that microglia promote astrocyte activation in aging. Since A1 reactive astrocytes lose the ability to carry out their normal functions, produce complement components, and release a toxic factor which kills neurons and oligodendrocytes, the aging-induced up-regulation of reactive genes by astrocytes could contribute to the cognitive decline in vulnerable brain regions in normal aging and contribute to the greater vulnerability of the aged brain to injury.}, } @article {pmid29437956, year = {2018}, author = {Noble, AE and Rosenstock, TS and Brown, PH and Machta, J and Hastings, A}, title = {Spatial patterns of tree yield explained by endogenous forces through a correspondence between the Ising model and ecology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1825-1830}, pmid = {29437956}, issn = {1091-6490}, mesh = {Agriculture/*methods ; *Models, Biological ; Pistacia/*physiology ; Plant Roots ; Seeds ; }, abstract = {Spatial patterning of periodic dynamics is a dramatic and ubiquitous ecological phenomenon arising in systems ranging from diseases to plants to mammals. The degree to which spatial correlations in cyclic dynamics are the result of endogenous factors related to local dynamics vs. exogenous forcing has been one of the central questions in ecology for nearly a century. With the goal of obtaining a robust explanation for correlations over space and time in dynamics that would apply to many systems, we base our analysis on the Ising model of statistical physics, which provides a fundamental mechanism of spatial patterning. We show, using 5 y of data on over 6,500 trees in a pistachio orchard, that annual nut production, in different years, exhibits both large-scale synchrony and self-similar, power-law decaying correlations consistent with the Ising model near criticality. Our approach demonstrates the possibility that short-range interactions can lead to long-range correlations over space and time of cyclic dynamics even in the presence of large environmental variability. We propose that root grafting could be the common mechanism leading to positive short-range interactions that explains the ubiquity of masting, correlated seed production over space through time, by trees.}, } @article {pmid29437955, year = {2018}, author = {Chuan, A and Kessler, JB and Milkman, KL}, title = {Field study of charitable giving reveals that reciprocity decays over time.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1766-1771}, pmid = {29437955}, issn = {1091-6490}, abstract = {We examine how reciprocity changes over time by studying a large quasiexperiment in the field. Specifically, we analyze administrative data from a university hospital system. The data include information about over 18,000 donation requests made by the hospital system via mail to a set of its former patients in the 4 months after their first hospital visit. We exploit quasiexperimental variation in the timing of solicitation mailings relative to patient hospital visits and find that an extra 30-day delay between the provision of medical care and a donation solicitation decreases the likelihood of a donation by 30%. Our findings have important implications for models of economic behavior, which currently fail to incorporate reciprocity's sensitivity to time. The fact that reciprocal behavior decays rapidly as time passes also suggests the importance of capitalizing quickly on opportunities to benefit from a quid pro quo.}, } @article {pmid29437954, year = {2018}, author = {Joglekar, AV and Liu, Z and Weber, JK and Ouyang, Y and Jeppson, JD and Noh, WJ and Lamothe-Molina, PA and Chen, H and Kang, SG and Bethune, MT and Zhou, R and Walker, BD and Baltimore, D}, title = {T cell receptors for the HIV KK10 epitope from patients with differential immunologic control are functionally indistinguishable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1877-1882}, pmid = {29437954}, issn = {1091-6490}, support = {P30 AI027763/AI/NIAID NIH HHS/United States ; P30 AI060354/AI/NIAID NIH HHS/United States ; U54 DK106829/DK/NIDDK NIH HHS/United States ; }, mesh = {CD8-Positive T-Lymphocytes/*physiology ; Cloning, Molecular ; Epitopes, T-Lymphocyte/*genetics ; Gene Expression Regulation/immunology ; HEK293 Cells ; HIV Infections/*immunology ; HIV-1/*immunology ; HLA-B27 Antigen ; Humans ; Jurkat Cells ; Receptors, Antigen, T-Cell/*genetics ; }, abstract = {HIV controllers (HCs) are individuals who can naturally control HIV infection, partially due to potent HIV-specific CD8+ T cell responses. Here, we examined the hypothesis that superior function of CD8+ T cells from HCs is encoded by their T cell receptors (TCRs). We compared the functional properties of immunodominant HIV-specific TCRs obtained from HLA-B*2705 HCs and chronic progressors (CPs) following expression in primary T cells. T cells transduced with TCRs from HCs and CPs showed equivalent induction of epitope-specific cytotoxicity, cytokine secretion, and antigen-binding properties. Transduced T cells comparably, albeit modestly, also suppressed HIV infection in vitro and in humanized mice. We also performed extensive molecular dynamics simulations that provided a structural basis for similarities in cytotoxicity and epitope cross-reactivity. These results demonstrate that the differential abilities of HIV-specific CD8+ T cells from HCs and CPs are not genetically encoded in the TCRs alone and must depend on additional factors.}, } @article {pmid29437953, year = {2018}, author = {Jenkitkasemwong, S and Akinyode, A and Paulus, E and Weiskirchen, R and Hojyo, S and Fukada, T and Giraldo, G and Schrier, J and Garcia, A and Janus, C and Giasson, B and Knutson, MD}, title = {SLC39A14 deficiency alters manganese homeostasis and excretion resulting in brain manganese accumulation and motor deficits in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1769-E1778}, pmid = {29437953}, issn = {1091-6490}, support = {R01 DK080706/DK/NIDDK NIH HHS/United States ; }, mesh = {Animal Feed/analysis ; Animals ; Biological Transport ; Brain/metabolism ; Cation Transport Proteins/deficiency/genetics/*metabolism ; Diet ; Hep G2 Cells ; Homeostasis ; Humans ; Manganese/administration & dosage/*metabolism ; Mice ; Mice, Knockout ; Motor Disorders/genetics/*metabolism ; Radioisotopes/metabolism ; }, abstract = {Solute carrier family 39, member 14 (SLC39A14) is a transmembrane transporter that can mediate the cellular uptake of zinc, iron, and manganese (Mn). Studies of Slc39a14 knockout (Slc39a14-/-) mice have documented that SLC39A14 is required for systemic growth, hepatic zinc uptake during inflammation, and iron loading of the liver in iron overload. The normal physiological roles of SLC39A14, however, remain incompletely characterized. Here, we report that Slc39a14-/- mice spontaneously display dramatic alterations in tissue Mn concentrations, suggesting that Mn is a main physiological substrate for SLC39A14. Specifically, Slc39a14-/- mice have abnormally low Mn levels in the liver coupled with markedly elevated Mn concentrations in blood and most other organs, especially the brain and bone. Radiotracer studies using 54Mn reveal that Slc39a14-/- mice have impaired Mn uptake by the liver and pancreas and reduced gastrointestinal Mn excretion. In the brain of Slc39a14-/- mice, Mn accumulated in the pons and basal ganglia, including the globus pallidus, a region susceptible to Mn-related neurotoxicity. Brain Mn accumulation in Slc39a14-/- mice was associated with locomotor impairments, as assessed by various behavioral tests. Although a low-Mn diet started at weaning was able to reverse brain Mn accumulation in Slc39a14-/- mice, it did not correct their motor deficits. We conclude that SLC39A14 is essential for efficient Mn uptake by the liver and pancreas, and its deficiency results in impaired Mn excretion and accumulation of the metal in other tissues. The inability of Mn depletion to correct the motor deficits in Slc39a14-/- mice suggests that the motor impairments represent lasting effects of early-life Mn exposure.}, } @article {pmid29437952, year = {2018}, author = {Haam, J and Zhou, J and Cui, G and Yakel, JL}, title = {Septal cholinergic neurons gate hippocampal output to entorhinal cortex via oriens lacunosum moleculare interneurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1886-E1895}, pmid = {29437952}, issn = {1091-6490}, mesh = {Acetylcholine/metabolism ; Animals ; Cholinergic Neurons/*cytology/metabolism ; Entorhinal Cortex/*cytology/metabolism ; Hippocampus/*cytology/metabolism ; Interneurons/*cytology/metabolism ; Male ; Mice ; Neural Pathways ; }, abstract = {Neuromodulation of neural networks, whereby a selected circuit is regulated by a particular modulator, plays a critical role in learning and memory. Among neuromodulators, acetylcholine (ACh) plays a critical role in hippocampus-dependent memory and has been shown to modulate neuronal circuits in the hippocampus. However, it has remained unknown how ACh modulates hippocampal output. Here, using in vitro and in vivo approaches, we show that ACh, by activating oriens lacunosum moleculare (OLM) interneurons and therefore augmenting the negative-feedback regulation to the CA1 pyramidal neurons, suppresses the circuit from the hippocampal area CA1 to the deep-layer entorhinal cortex (EC). We also demonstrate, using mouse behavior studies, that the ablation of OLM interneurons specifically impairs hippocampus-dependent but not hippocampus-independent learning. These data suggest that ACh plays an important role in regulating hippocampal output to the EC by activating OLM interneurons, which is critical for the formation of hippocampus-dependent memory.}, } @article {pmid29436719, year = {2018}, author = {Marchini, M and Rolian, C}, title = {Artificial selection sheds light on developmental mechanisms of limb elongation.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {825-837}, doi = {10.1111/evo.13447}, pmid = {29436719}, issn = {1558-5646}, abstract = {Species diversity in limb lengths and proportions is thought to have evolved adaptively in the context of locomotor and habitat specialization, but the heritable cellular processes that drove this evolution within species are poorly understood. In this study, we take a novel "micro-evo-devo" approach, using artificial selection on relative limb length to amplify phenotypic variation in a population of mice, known as Longshanks, to examine the cellular mechanisms of postnatal limb development that contribute to intraspecific limb length variation. Cross-sectional growth data indicate that differences in bone length between Longshanks and random-bred controls are not due to prolonged growth, but to accelerated growth rates. Histomorphometric and cell proliferation assays on proximal tibial growth plates show that Longshanks' increased limb bone length is associated with an increased number of proliferative chondrocytes. In contrast, we find no differences in other growth plate cellular features known to underlie interspecific differences in limb bone size and shape, such as the rates of chondrocyte proliferation or the size and number of hypertrophic cells in the growth plate. These data suggest that small differences among individuals in the number of proliferating chondrocytes are a potentially important determinant of selectable intraspecific variation in individual limb bone lengths, independent of body size.}, } @article {pmid29436097, year = {2018}, author = {Upadhyay, A and Mishra, A}, title = {Amyloids of multiple species: are they helpful in survival?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1363-1386}, doi = {10.1111/brv.12399}, pmid = {29436097}, issn = {1469-185X}, abstract = {Amyloids are primarily known for their roles in neurodegenerative disorders, as well as in systemic diseases like diabetes. Evolutionary forces tend to maintain a healthy set of heritable characteristics, while eliminating toxic or unfavourable elements; but amyloids seem to represent an exception to this fundamental concept. In addition to their presence in mammals, amyloids also persist in the proteome of many lower organisms that may be linked with possible roles in survival, which are still unexplored. Herein, we address some unanswered questions regarding amyloids: are these well-structured proteinaceous aggregates a by-product of inefficient folding events, or have they been retained in our protein repertoire for as yet unknown functional roles; and how do protein misfolding and associated disorders originate, despite the presence of protein quality-control systems inside the cells? This review aims to extend our current understanding about the multifaceted useful properties of amyloids and their functional interactions with other molecular pathways in various species; this may provide new insights to identify novel therapeutic strategies for ageing and neurodegenerative diseases.}, } @article {pmid29435612, year = {2018}, author = {Agustí, G and Fittipaldi, M and Codony, F}, title = {Optimization of a Viability PCR Method for the Detection of Listeria monocytogenes in Food Samples.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {779-785}, pmid = {29435612}, issn = {1432-0991}, mesh = {DNA, Bacterial/*genetics ; Food Microbiology/methods ; Listeria monocytogenes/*genetics ; Polymerase Chain Reaction/*methods ; }, abstract = {Rapid detection of Listeria and other microbial pathogens in food is an essential part of quality control and it is critical for ensuring the safety of consumers. Culture-based methods for detecting foodborne pathogens are time-consuming, laborious and cannot detect viable but non-culturable microorganism, whereas viability PCR methodology provides quick results; it is able to detect viable but non-culturable cells, and allows for easier handling of large amount of samples. Although the most critical point to use viability PCR technique is achieving the complete exclusion of dead cell amplification signals, many improvements are being introduced to overcome this. In the present work, the yield of dead cell DNA neutralization was enhanced by incorporating two new sample treatment strategies: tube change combined with a double light treatment. This procedure was successfully tested using artificially contaminated food samples, showing improved neutralization of dead cell DNA.}, } @article {pmid29435264, year = {2018}, author = {Wilson, SK and Depcyznski, M and Fisher, R and Holmes, TH and Noble, MM and Radford, BT and Rule, M and Shedrawi, G and Tinkler, P and Fulton, CJ}, title = {Climatic forcing and larval dispersal capabilities shape the replenishment of fishes and their habitat-forming biota on a tropical coral reef.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1918-1928}, pmid = {29435264}, issn = {2045-7758}, abstract = {Fluctuations in marine populations often relate to the supply of recruits by oceanic currents. Variation in these currents is typically driven by large-scale changes in climate, in particular ENSO (El Nino Southern Oscillation). The dependence on large-scale climatic changes may, however, be modified by early life history traits of marine taxa. Based on eight years of annual surveys, along 150 km of coastline, we examined how ENSO influenced abundance of juvenile fish, coral spat, and canopy-forming macroalgae. We then investigated what traits make populations of some fish families more reliant on the ENSO relationship than others. Abundance of juvenile fish and coral recruits was generally positively correlated with the Southern Oscillation Index (SOI), higher densities recorded during La Niña years, when the ENSO-influenced Leeuwin Current is stronger and sea surface temperature higher. The relationship is typically positive and stronger among fish families with shorter pelagic larval durations and stronger swimming abilities. The relationship is also stronger at sites on the coral back reef, although the strongest of all relationships were among the lethrinids (r = .9), siganids (r = .9), and mullids (r = .8), which recruit to macroalgal meadows in the lagoon. ENSO effects on habitat seem to moderate SOI-juvenile abundance relationship. Macroalgal canopies are higher during La Niña years, providing more favorable habitat for juvenile fish and strengthening the SOI effect on juvenile abundance. Conversely, loss of coral following a La Niña-related heat wave may have compromised postsettlement survival of coral dependent species, weakening the influence of SOI on their abundance. This assessment of ENSO effects on tropical fish and habitat-forming biota and how it is mediated by functional ecology improves our ability to predict and manage changes in the replenishment of marine populations.}, } @article {pmid29435263, year = {2018}, author = {Hardy, MA and Hull, SD and Zuckerberg, B}, title = {Swift action increases the success of population reinforcement for a declining prairie grouse.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1906-1917}, pmid = {29435263}, issn = {2045-7758}, abstract = {Translocations have become an increasingly valuable tool for conservation in recent years, but assessing the successfulness of translocations and identifying factors that contribute to their success continue to challenge biologists. As a unique class of translocation, population reinforcements have received relatively little attention despite representing a substantial portion of translocation programs. Here, we conducted population viability analyses to quantify the effects of 216 reinforcement scenarios on the long-term viability of four populations of Greater Prairie-Chickens (Tympanuchus cupido pinnatus) in Wisconsin, USA, and used multiple linear regression to identify factors that had the greatest relative influence on population viability. We considered reinforcements from outside of the study area in addition to translocations among Wisconsin populations. We observed the largest decreases in site-specific extinction probability and the largest increases in the number of sites persisting for 50 years when more vulnerable populations were targeted for reinforcement. Conversely, reinforcing the most stable sites caused the greatest reduction in regional extinction probability. We found that the number of translocated hens was a comparatively poor predictor of changes in long-term population viability, whereas the earlier onset of reinforcement was consistently associated with the greatest increases in viability. Our results highlight the value of evaluating alternative reinforcement strategies a priori and considering the effects of reinforcement on metrics of long-term population persistence.}, } @article {pmid29435262, year = {2018}, author = {Derryberry, EP and Seddon, N and Derryberry, GE and Claramunt, S and Seeholzer, GF and Brumfield, RT and Tobias, JA}, title = {Ecological drivers of song evolution in birds: Disentangling the effects of habitat and morphology.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1890-1905}, pmid = {29435262}, issn = {2045-7758}, abstract = {Environmental differences influence the evolutionary divergence of mating signals through selection acting either directly on signal transmission ("sensory drive") or because morphological adaptation to different foraging niches causes divergence in "magic traits" associated with signal production, thus indirectly driving signal evolution. Sensory drive and magic traits both contribute to variation in signal structure, yet we have limited understanding of the relative role of these direct and indirect processes during signal evolution. Using phylogenetic analyses across 276 species of ovenbirds (Aves: Furnariidae), we compared the extent to which song evolution was related to the direct influence of habitat characteristics and the indirect effect of body size and beak size, two potential magic traits in birds. We find that indirect ecological selection, via diversification in putative magic traits, explains variation in temporal, spectral, and performance features of song. Body size influences song frequency, whereas beak size limits temporal and performance components of song. In comparison, direct ecological selection has weaker and more limited effects on song structure. Our results illustrate the importance of considering multiple deterministic processes in the evolution of mating signals.}, } @article {pmid29435261, year = {2018}, author = {Thurman, TJ and Brodie, E and Evans, E and McMillan, WO}, title = {Facultative pupal mating in Heliconius erato: Implications for mate choice, female preference, and speciation.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1882-1889}, pmid = {29435261}, issn = {2045-7758}, abstract = {Mating systems have broad impacts on how sexual selection and mate choice operate within a species, but studies of mating behavior in the laboratory may not reflect how these processes occur in the wild. Here, we examined the mating behavior of the neotropical butterfly Heliconius erato in the field by releasing larvae and virgin females and observing how they mated. H. erato is considered a pupal-mating species (i.e., males mate with females as they emerge from the pupal case). However, we observed only two teneral mating events, and experimentally released virgins were almost all mated upon recapture. Our study confirms the presence of some pupal-mating behavior in H. erato, but suggests that adult mating is likely the prevalent mating strategy in this species. These findings have important implications for the role of color pattern and female mate choice in the generation of reproductive isolation in this diverse genus.}, } @article {pmid29435260, year = {2018}, author = {Mason, NA and Olvera-Vital, A and Lovette, IJ and Navarro-Sigüenza, AG}, title = {Hidden endemism, deep polyphyly, and repeated dispersal across the Isthmus of Tehuantepec: Diversification of the White-collared Seedeater complex (Thraupidae: Sporophila torqueola).}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1867-1881}, pmid = {29435260}, issn = {2045-7758}, abstract = {Phenotypic and genetic variation are present in all species, but lineages differ in how variation is partitioned among populations. Examining phenotypic clustering and genetic structure within a phylogeographic framework can clarify which biological processes have contributed to extant biodiversity in a given lineage. Here, we investigate genetic and phenotypic variation among populations and subspecies within a Neotropical songbird complex, the White-collared Seedeater (Sporophila torqueola) of Central America and Mexico. We combine measurements of morphology and plumage patterning with thousands of nuclear loci derived from ultraconserved elements (UCEs) and mitochondrial DNA to evaluate population differentiation. We find deep levels of molecular divergence between two S. torqueola lineages that are phenotypically diagnosable: One corresponds to S. t. torqueola along the Pacific coast of Mexico, and the other includes S. t. morelleti and S. t. sharpei from the Gulf Coast of Mexico and Central America. Surprisingly, these two lineages are strongly differentiated in both nuclear and mitochondrial markers, and each is more closely related to other Sporophila species than to one another. We infer low levels of gene flow between these two groups based on demographic models, suggesting multiple independent evolutionary lineages within S. torqueola have been obscured by coarse-scale similarity in plumage patterning. These findings improve our understanding of the biogeographic history of this lineage, which includes multiple dispersal events out of South America and across the Isthmus of Tehuantepec into Mesoamerica. Finally, the phenotypic and genetic distinctiveness of the range-restricted S. t. torqueola highlights the Pacific Coast of Mexico as an important region of endemism and conservation priority.}, } @article {pmid29435259, year = {2018}, author = {Mitchell, N and Carlson, JE and Holsinger, KE}, title = {Correlated evolution between climate and suites of traits along a fast-slow continuum in the radiation of Protea.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1853-1866}, pmid = {29435259}, issn = {2045-7758}, abstract = {Evolutionary radiations are responsible for much of Earth's diversity, yet the causes of these radiations are often elusive. Determining the relative roles of adaptation and geographic isolation in diversification is vital to understanding the causes of any radiation, and whether a radiation may be labeled as "adaptive" or not. Across many groups of plants, trait-climate relationships suggest that traits are an important indicator of how plants adapt to different climates. In particular, analyses of plant functional traits in global databases suggest that there is an "economics spectrum" along which combinations of functional traits covary along a fast-slow continuum. We examine evolutionary associations among traits and between trait and climate variables on a strongly supported phylogeny in the iconic plant genus Protea to identify correlated evolution of functional traits and the climatic-niches that species occupy. Results indicate that trait diversification in Protea has climate associations along two axes of variation: correlated evolution of plant size with temperature and leaf investment with rainfall. Evidence suggests that traits and climatic-niches evolve in similar ways, although some of these associations are inconsistent with global patterns on a broader phylogenetic scale. When combined with previous experimental work suggesting that trait-climate associations are adaptive in Protea, the results presented here suggest that trait diversification in this radiation is adaptive.}, } @article {pmid29435258, year = {2018}, author = {Losdat, S and Germain, RR and Nietlisbach, P and Arcese, P and Reid, JM}, title = {No evidence of inbreeding depression in sperm performance traits in wild song sparrows.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1842-1852}, pmid = {29435258}, issn = {2045-7758}, abstract = {Inbreeding is widely hypothesized to shape mating systems and population persistence, but such effects will depend on which traits show inbreeding depression. Population and evolutionary consequences could be substantial if inbreeding decreases sperm performance and hence decreases male fertilization success and female fertility. However, the magnitude of inbreeding depression in sperm performance traits has rarely been estimated in wild populations experiencing natural variation in inbreeding. Further, the hypothesis that inbreeding could increase within-ejaculate variation in sperm traits and thereby further affect male fertilization success has not been explicitly tested. We used a wild pedigreed song sparrow (Melospiza melodia) population, where frequent extrapair copulations likely create strong postcopulatory competition for fertilization success, to quantify effects of male coefficient of inbreeding (f) on key sperm performance traits. We found no evidence of inbreeding depression in sperm motility, longevity, or velocity, and the within-ejaculate variance in sperm velocity did not increase with male f. Contrary to inferences from highly inbred captive and experimental populations, our results imply that moderate inbreeding will not necessarily constrain sperm performance in wild populations. Consequently, the widely observed individual-level and population-level inbreeding depression in male and female fitness may not stem from reduced sperm performance in inbred males.}, } @article {pmid29435257, year = {2018}, author = {Schmidt, JH and McIntyre, CL and Roland, CA and MacCluskie, MC and Flamme, MJ}, title = {Bottom-up processes drive reproductive success in an apex predator.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1833-1841}, pmid = {29435257}, issn = {2045-7758}, abstract = {One of the central goals of the field of population ecology is to identify the drivers of population dynamics, particularly in the context of predator-prey relationships. Understanding the relative role of top-down versus bottom-up drivers is of particular interest in understanding ecosystem dynamics. Our goal was to explore predator-prey relationships in a boreal ecosystem in interior Alaska through the use of multispecies long-term monitoring data. We used 29 years of field data and a dynamic multistate site occupancy modeling approach to explore the trophic relationships between an apex predator, the golden eagle, and cyclic populations of the two primary prey species available to eagles early in the breeding season, snowshoe hare and willow ptarmigan. We found that golden eagle reproductive success was reliant on prey numbers, but also responded prior to changes in the phase of the snowshoe hare population cycle and failed to respond to variation in hare cycle amplitude. There was no lagged response to ptarmigan populations, and ptarmigan populations recovered quickly from the low phase. Together, these results suggested that eagle reproduction is largely driven by bottom-up processes, with little evidence of top-down control of either ptarmigan or hare populations. Although the relationship between golden eagle reproductive success and prey abundance had been previously established, here we established prey populations are likely driving eagle dynamics through bottom-up processes. The key to this insight was our focus on golden eagle reproductive parameters rather than overall abundance. Although our inference is limited to the golden eagle-hare-ptarmigan relationships we studied, our results suggest caution in interpreting predator-prey abundance patterns among other species as strong evidence for top-down control.}, } @article {pmid29435256, year = {2018}, author = {Leite, DCA and Salles, JF and Calderon, EN and van Elsas, JD and Peixoto, RS}, title = {Specific plasmid patterns and high rates of bacterial co-occurrence within the coral holobiont.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1818-1832}, pmid = {29435256}, issn = {2045-7758}, abstract = {Despite the importance of coral microbiomes for holobiont persistence, the interactions among these are not well understood. In particular, knowledge of the co-occurrence and taxonomic importance of specific members of the microbial core, as well as patterns of specific mobile genetic elements (MGEs), is lacking. We used seawater and mucus samples collected from Mussismilia hispida colonies on two reefs located in Bahia, Brazil, to disentangle their associated bacterial communities, intertaxa correlations, and plasmid patterns. Proxies for two broad-host-range (BHR) plasmid groups, IncP-1β and PromA, were screened. Both groups were significantly (up to 252 and 100%, respectively) more abundant in coral mucus than in seawater. Notably, the PromA plasmid group was detected only in coral mucus samples. The core bacteriome of M. hispida mucus was composed primarily of members of the Proteobacteria, followed by those of Firmicutes. Significant host specificity and co-occurrences among different groups of the dominant phyla (e.g., Bacillaceae and Pseudoalteromonadaceae and the genera Pseudomonas, Bacillus, and Vibrio) were detected. These relationships were observed for both the most abundant phyla and the bacteriome core, in which most of the operational taxonomic units showed intertaxa correlations. The observed evidence of host-specific bacteriome and co-occurrence (and potential symbioses or niche space co-dominance) among the most dominant members indicates a taxonomic selection of members of the stable bacterial community. In parallel, host-specific plasmid patterns could also be, independently, related to the assembly of members of the coral microbiome.}, } @article {pmid29435255, year = {2018}, author = {Crespo, D and Solan, M and Leston, S and Pardal, MA and Dolbeth, M}, title = {Ecological consequences of invasion across the freshwater-marine transition in a warming world.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1807-1817}, pmid = {29435255}, issn = {2045-7758}, abstract = {The freshwater-marine transition that characterizes an estuarine system can provide multiple entry options for invading species, yet the relative importance of this gradient in determining the functional contribution of invading species has received little attention. The ecological consequences of species invasion are routinely evaluated within a freshwater versus marine context, even though many invasive species can inhabit a wide range of salinities. We investigate the functional consequences of different sizes of Corbicula fluminea-an invasive species able to adapt to a wide range of temperatures and salinity-across the freshwater-marine transition in the presence versus absence of warming. Specifically, we characterize how C. fluminea affect fluid and particle transport, important processes in mediating nutrient cycling (NH 4-N, NO 3-N, PO 4-P). Results showed that sediment particle reworking (bioturbation) tends to be influenced by size and to a lesser extent, temperature and salinity; nutrient concentrations are influenced by different interactions between all variables (salinity, temperature, and size class). Our findings demonstrate the highly context-dependent nature of the ecosystem consequences of invasion and highlight the potential for species to simultaneously occupy multiple components of an ecosystem. Recognizing of this aspect of invasibility is fundamental to management and conservation efforts, particularly as freshwater and marine systems tend to be compartmentalized rather than be treated as a contiguous unit. We conclude that more comprehensive appreciation of the distribution of invasive species across adjacent habitats and different seasons is urgently needed to allow the true extent of biological introductions, and their ecological consequences, to be fully realized.}, } @article {pmid29435254, year = {2018}, author = {Leempoel, K and Parisod, C and Geiser, C and Joost, S}, title = {Multiscale landscape genomic models to detect signatures of selection in the alpine plant Biscutella laevigata.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1794-1806}, pmid = {29435254}, issn = {2045-7758}, abstract = {Plant species are known to adapt locally to their environment, particularly in mountainous areas where conditions can vary drastically over short distances. The climate of such landscapes being largely influenced by topography, using fine-scale models to evaluate environmental heterogeneity may help detecting adaptation to micro-habitats. Here, we applied a multiscale landscape genomic approach to detect evidence of local adaptation in the alpine plant Biscutella laevigata. The two gene pools identified, experiencing limited gene flow along a 1-km ridge, were different in regard to several habitat features derived from a very high resolution (VHR) digital elevation model (DEM). A correlative approach detected signatures of selection along environmental gradients such as altitude, wind exposure, and solar radiation, indicating adaptive pressures likely driven by fine-scale topography. Using a large panel of DEM-derived variables as ecologically relevant proxies, our results highlighted the critical role of spatial resolution. These high-resolution multiscale variables indeed indicate that the robustness of associations between genetic loci and environmental features depends on spatial parameters that are poorly documented. We argue that the scale issue is critical in landscape genomics and that multiscale ecological variables are key to improve our understanding of local adaptation in highly heterogeneous landscapes.}, } @article {pmid29435253, year = {2018}, author = {Bálint, M and Márton, O and Schatz, M and Düring, RA and Grossart, HP}, title = {Proper experimental design requires randomization/balancing of molecular ecology experiments.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1786-1793}, pmid = {29435253}, issn = {2045-7758}, abstract = {Properly designed (randomized and/or balanced) experiments are standard in ecological research. Molecular methods are increasingly used in ecology, but studies generally do not report the detailed design of sample processing in the laboratory. This may strongly influence the interpretability of results if the laboratory procedures do not account for the confounding effects of unexpected laboratory events. We demonstrate this with a simple experiment where unexpected differences in laboratory processing of samples would have biased results if randomization in DNA extraction and PCR steps do not provide safeguards. We emphasize the need for proper experimental design and reporting of the laboratory phase of molecular ecology research to ensure the reliability and interpretability of results.}, } @article {pmid29435252, year = {2018}, author = {O'Kelly, HJ and Rowcliffe, JM and Durant, S and Milner-Gulland, EJ}, title = {Experimental estimation of snare detectability for robust threat monitoring.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1778-1785}, pmid = {29435252}, issn = {2045-7758}, abstract = {Hunting with wire snares is rife within many tropical forest systems, and constitutes one of the severest threats to a wide range of vertebrate taxa. As for all threats, reliable monitoring of snaring levels is critical for assessing the relative effectiveness of management interventions. However, snares pose a particular challenge in terms of tracking spatial or temporal trends in their prevalence because they are extremely difficult to detect, and are typically spread across large, inaccessible areas. As with cryptic animal targets, any approach used to monitor snaring levels must address the issue of imperfect detection, but no standard method exists to do so. We carried out a field experiment in Keo Seima Wildlife Reserve in eastern Cambodia with the following objectives: (1) To estimate the detection probably of wire snares within a tropical forest context, and to investigate how detectability might be affected by habitat type, snare type, or observer. (2) To trial two sets of sampling protocols feasible to implement in a range of challenging field conditions. (3) To conduct a preliminary assessment of two potential analytical approaches to dealing with the resulting snare encounter data. We found that although different observers had no discernible effect on detection probability, detectability did vary between habitat type and snare type. We contend that simple repeated counts carried out at multiple sites and analyzed using binomial mixture models could represent a practical yet robust solution to the problem of monitoring snaring levels both inside and outside of protected areas. This experiment represents an important first step in developing improved methods of threat monitoring, and such methods are greatly needed in southeast Asia, as well as in as many other regions.}, } @article {pmid29435251, year = {2018}, author = {He, X and Houde, ALS and Neff, BD and Heath, DD}, title = {Transcriptome response of Atlantic salmon (Salmo salar) to competition with ecologically similar non-native species.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1769-1777}, pmid = {29435251}, issn = {2045-7758}, abstract = {Non-native species may be introduced either intentionally or unintentionally, and their impact can range from benign to highly disruptive. Non-native salmonids were introduced into Lake Ontario, Canada, to provide recreational fishing opportunities; however, the establishment of those species has been proposed as a significant barrier to the reintroduction of native Atlantic salmon (Salmo salar) due to intense interspecific competition. In this study, we compared population differences of Atlantic salmon in transcriptome response to interspecific competition. We reared Atlantic salmon from two populations (LaHave River and Sebago Lake) with fish of each of three non-native salmonids (Chinook salmon Oncorhynchus tshawytscha, rainbow trout O. mykiss, and brown trout S. trutta) in artificial streams. We used RNA-seq to assess transcriptome differences between the Atlantic salmon populations and the responses of these populations to the interspecific competition treatments after 10 months of competition in the stream tanks. We found that population differences in gene expression were generally greater than the effects of interspecific competition. Interestingly, we found that the two Atlantic salmon populations exhibited similar responses to interspecific competition based on functional gene ontologies, but the specific genes within those ontologies were different. Our transcriptome analyses suggest that the most stressful competitor (as measured by the highest number of differentially expressed genes) differs between the two study populations. Our transcriptome characterization highlights the importance of source population selection for conservation applications, as organisms with different evolutionary histories can possess different transcriptional responses to the same biotic stressors. The results also indicate that generalized predictions of the response of native species to interactions with introduced species may not be appropriate without incorporating potential population-specific response to introduced species.}, } @article {pmid29435250, year = {2018}, author = {Sebastian-Azcona, J and Hacke, UG and Hamann, A}, title = {Adaptations of white spruce to climate: strong intraspecific differences in cold hardiness linked to survival.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1758-1768}, pmid = {29435250}, issn = {2045-7758}, abstract = {Understanding local adaptation of tree populations to climate allows the development of assisted migration guidelines as a tool for forest managers to address climate change. Here, we study the relationship among climate, a wide range of physiological traits, and field performance of selected white spruce provenances originating from throughout the species range. Tree height, survival, cold hardiness, hydraulic, and wood anatomical traits were measured in a 32-year-old common garden trial, located in the center of the species range. Provenance performance included all combinations of high versus low survival and growth, with the most prevalent population differentiation for adaptive traits observed in cold hardiness. Cold hardiness showed a strong association with survival and was associated with cold winter temperatures at the site of seed origin. Tree height was mostly explained by the length of the growing season at the origin of the seed source. Although population differentiation was generally weak in wood anatomical and hydraulic traits, within-population variation was substantial in some traits, and a boundary analysis revealed that efficient water transport was associated with vulnerable xylem and low wood density, indicating that an optimal combination of high water transport efficiency and high cavitation resistance is not possible. Our results suggest that assisted migration prescriptions may be advantageous under warming climate, but pronounced trade-offs between survival and cold hardiness require a careful consideration of the distances of these transfers.}, } @article {pmid29435249, year = {2018}, author = {Matsuo, A and Tomimatsu, H and Sangetsu, Y and Suyama, Y and Makita, A}, title = {Genet dynamics of a regenerating dwarf bamboo population across heterogeneous light environments in a temperate forest understorey.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1746-1757}, pmid = {29435249}, issn = {2045-7758}, abstract = {Despite the advantage of plant clonality in patchy environments, studies focusing on genet demography in relation to spatially heterogeneous environments remain scarce. Regeneration of bamboos in forest understoreys after synchronous die-off provides an opportunity for assessing how they come to proliferate across heterogeneous light environments. In a Japanese forest, we examined genet demography of a population of Sasa kurilensis over a 7-year period starting 10 years after die-off, shortly after which some genets began spreading horizontally by rhizomes. The aboveground biomass was estimated, and genets were discriminated in 9-m2 plots placed under both canopy gaps and closed canopies. Overall, the results suggest that the survival and spread of more productive genets and the spatial expansion of genets into closed canopies underlie the proliferation of S. kurilensis. Compared to canopy gaps, the recovery rate of biomass was much slower under closed canopies for the first 10 years after the die-off, but became accelerated during the next 7 years. Genet survival was greater for more productive genets (with greater initial number of culms), and the spaces occupied by genets that died were often colonized afterward by clonal growth of surviving genets. The number of genets decreased under canopy gaps due to greater mortality, but increased under closed canopies where greater number of genets colonized clonally from outside the plots than genets died. The colonizing genets were more productive (having larger culms) than those originally germinated within the plots, and the contribution of colonizing genets to the biomass was greater under closed canopies. Our study emphasizes the importance of investigating genet dynamics over relevant spatiotemporal scales to reveal processes underlying the success of clonal plants in heterogeneous habitats.}, } @article {pmid29435248, year = {2018}, author = {Liu, G and Shafer, ABA and Hu, X and Li, L and Ning, Y and Gong, M and Cui, L and Li, H and Hu, D and Qi, L and Tian, H and Wang, B}, title = {Meta-barcoding insights into the spatial and temporal dietary patterns of the threatened Asian Great Bustard (Otis tarda dybowskii) with potential implications for diverging migratory strategies.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1736-1745}, pmid = {29435248}, issn = {2045-7758}, abstract = {Food resources are often not sufficient to satisfy the nutritional and energetic requirements during winter conditions at high latitudes. Dietary analysis is a prerequisite to fully understanding the feeding ecology of a species and the nature of trophic interactions. Previous dietary studies of Asian Great Bustard (Otis tarda dybowskii) relied on behavioral observations, resulting in categorization of diet limited to broad taxonomic groupings. Here, we applied a high-throughput sequencing meta-barcoding approach to quantify the diet of resident and migratory Asian Great Bustard in three wintering sites during early winter and late winter. We detected 57 unique plant taxa in the bustard diet, among which 15 species were confirmed by a local plant database we generated. Both agricultural and natural foods were detected, indicating a relatively broad dietary niche. Spatiotemporal dietary changes were discovered, revealing diet differences among wintering sites and a general shift toward lower plant diversity later in winter. For the nonmigratory population, we detected a significantly more diverse array of plant species in their diet. We hypothesize that dietary variation between resident and migratory populations could be involved in the recent transition to partial migration in this species, although climate change can not be excluded. Collectively, these results support protecting unharvested grain fields and naturally unplowed lands to help conserve and promote population growth of Asian Great Bustard.}, } @article {pmid29435247, year = {2018}, author = {Ikeda, H and Fukumori, K and Shoda-Kagaya, E and Takahashi, M and Ito, MT and Sakai, Y and Matsumoto, K}, title = {Evolution of a key trait greatly affects underground community assembly process through habitat adaptation in earthworms.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1726-1735}, pmid = {29435247}, issn = {2045-7758}, abstract = {Underground community assemblies have not been studied well compared with aboveground communities, despite their importance for our understanding of whole ecosystems. To investigate underground community assembly over evolutionary timescales, we examined terrestrial earthworm communities (Oligochaeta: Haplotaxida) in conserved mountainous primary forests in Japan as a model system. We collected 553 earthworms mostly from two dominant families, the Megascolecidae and the Lumbricidae, from 12 sites. We constructed a molecular taxonomic unit tree based on the analysis of three genes to examine the effects of a biogeographic factor (dispersal ability) and an evolutionary factor (habitat adaptation) on the earthworm community assembly process. The phylogenetic distance of the earthworm communities among sites was positively correlated with geographic distance when intraspecific variation was included, indicating that the divergence within species was affected by biogeographic factors. The community assembly process in the Megascolecidae has also been affected by environmental conditions in relation to an evolutionary relationship between habitat environment and intestinal cecum type, a trait closely related to habitat depth and diet, whereas that in the Lumbricidae has not been affected as such. Intestinal cecum type showed a pattern of niche conservatism in the Megascolecidae lineage. Our results suggest that investigating the evolution of a key trait related to life history can lead to the clear description of community assembly process over a long timescale and that the community assembly process can differ greatly among related lineages even though they live sympatrically.}, } @article {pmid29435246, year = {2018}, author = {Patykowski, J and Holland, GJ and Dell, M and Wevill, T and Callister, K and Bennett, AF and Gibson, M}, title = {The effect of prescribed burning on plant rarity in a temperate forest.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1714-1725}, pmid = {29435246}, issn = {2045-7758}, abstract = {Rare species can play important functional roles, but human-induced changes to disturbance regimes, such as fire, can inadvertently affect these species. We examined the influence of prescribed burns on the recruitment and diversity of plant species within a temperate forest in southeastern Australia, with a focus on species that were rare prior to burning. Floristic composition was compared among plots in landscapes before and after treatment with prescribed burns differing in the extent of area burnt and season of burn (before-after, control-impact design). Floristic surveys were conducted before burns, at the end of a decade of drought, and 3 years postburn. We quantified the effect of prescribed burns on species grouped by their frequency within the landscape before burning (common, less common, and rare) and their life-form attributes (woody perennials, perennial herbs or geophytes, and annual herbs). Burn treatment influenced the response of rare species. In spring-burn plots, the recruitment of rare annual herbs was promoted, differentiating this treatment from both autumn-burn and unburnt plots. In autumn-burn plots, richness of rare species increased across all life-form groups, although composition remained statistically similar to control plots. Richness of rare woody perennials increased in control plots. For all other life-form and frequency groups, the floristic composition of landscapes changed between survey years, but there was no effect of burn treatment, suggesting a likely effect of rainfall on species recruitment. A prescribed burn can increase the occurrence of rare species in a landscape, but burn characteristics can affect the promotion of different life-form groups and thus affect functional diversity. Drought-breaking rain likely had an overarching effect on floristic composition during our study, highlighting that weather can play a greater role in influencing recruitment and diversity in plant communities than a prescribed burn.}, } @article {pmid29435245, year = {2018}, author = {Liu, X and Chen, F and Lyu, S and Sun, D and Zhou, S}, title = {Random species loss underestimates dilution effects of host diversity on foliar fungal diseases under fertilization.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1705-1713}, pmid = {29435245}, issn = {2045-7758}, abstract = {With increasing attention being paid to the consequences of global biodiversity losses, several recent studies have demonstrated that realistic species losses can have larger impacts than random species losses on community productivity and resilience. However, little is known about the effects of the order in which species are lost on biodiversity-disease relationships. Using a multiyear nitrogen addition and artificial warming experiment in natural assemblages of alpine meadow vegetation on the Qinghai-Tibetan Plateau, we inferred the sequence of plant species losses under fertilization/warming. Then the sequence of species losses under fertilization/warming was used to simulate the species loss orders (both realistic and random) in an adjacently novel removal experiment manipulating plot-level plant diversity. We explicitly compared the effect sizes of random versus realistic species losses simulated from fertilization/warming on plant foliar fungal diseases. We found that realistic species losses simulated from fertilization had greater effects than random losses on fungal diseases, and that species identity drove the diversity-disease relationship. Moreover, the plant species most prone to foliar fungal diseases were also the least vulnerable to extinction under fertilization, demonstrating the importance of protecting low competence species (the ability to maintain and transmit fungal infections was low) to impede the spread of infectious disease. In contrast, there was no difference between random and realistic species loss scenarios simulated from experimental warming (or the combination of warming and fertilization) on the diversity-disease relationship, indicating that the functional consequences of species losses may vary under different drivers.}, } @article {pmid29435244, year = {2018}, author = {Wang, S and Zuo, X and Zhao, X and Awada, T and Luo, Y and Li, Y and Qu, H}, title = {Dominant plant species shape soil bacterial community in semiarid sandy land of northern China.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1693-1704}, pmid = {29435244}, issn = {2045-7758}, abstract = {Plant species affect soil bacterial diversity and compositions. However, little is known about the role of dominant plant species in shaping the soil bacterial community during the restoration of sandy grasslands in Horqin Sandy Land, northern China. We established a mesocosm pots experiment to investigate short-term responses of soil bacterial diversity and composition, and the related soil properties in degraded soils without vegetation (bare sand as the control, CK) to restoration with five plant species that dominate across restoration stages: Agriophyllum squarrosum (AS), Artemisia halodendron (AH), Setaria viridis (SV), Chenopodium acuminatum (CA), and Corispermum macrocarpum (CM). We used redundancy analysis (RDA) to analyze the association between soil bacterial composition and soil properties in different plant species. Our results indicated that soil bacterial diversity was significantly lower in vegetated soils independent of plant species than in the CK. Specifically, soil bacterial species richness and diversity were lower under the shrub AH and the herbaceous plants AS, SV, and CA, and soil bacterial abundance was lower under AH compared with the CK. A field investigation confirmed the same trends where soil bacteria diversity was lower under AS and AH than in bare sand. The high-sequence annotation analysis showed that Proteobacteria, Actinobacteria, and Bacteroidetes were the most common phyla in sandy land irrespective of soil plant cover. The OTUs (operational taxonomic units) indicated that some bacterial species were specific to the host plants. Relative to bare sand (CK), soils with vegetative cover exhibited lower soil water content and temperature, and higher soil carbon and nitrogen contents. The RDA result indicated that, in addition to plant species, soil water and nitrogen contents were the most important factors shaping soil bacterial composition in semiarid sandy land. Our study from the pot and field investigations clearly demonstrated that planting dominant species in bare sand impacts bacterial diversity. In semiarid ecosystems, changes in the dominant plant species during vegetation restoration efforts can affect the soil bacterial diversity and composition through the direct effects of plants and the indirect effects of soil properties that are driven by plant species.}, } @article {pmid29435243, year = {2018}, author = {Rekdal, SL and Anmarkrud, JA and Johnsen, A and Lifjeld, JT}, title = {Genotyping strategy matters when analyzing hypervariable major histocompatibility complex-Experience from a passerine bird.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1680-1692}, pmid = {29435243}, issn = {2045-7758}, abstract = {Genotyping of classical major histocompatibility complex (MHC) genes is challenging when they are hypervariable and occur in multiple copies. In this study, we used several different approaches to genotype the moderately variable MHC class I exon 3 (MHCIe3) and the highly polymorphic MHC class II exon 2 (MHCIIβe2) in the bluethroat (Luscinia svecica). Two family groups (eight individuals) were sequenced in replicates at both markers using Ion Torrent technology with both a single- and a dual-indexed primer structure. Additionally, MHCIIβe2 was sequenced on Illumina MiSeq. Allele calling was conducted by modifications of the pipeline developed by Sommer et al. (BMC Genomics, 14, 2013, 542) and the software AmpliSAS. While the different genotyping strategies gave largely consistent results for MHCIe3, with a maximum of eight alleles per individual, MHCIIβe2 was remarkably complex with a maximum of 56 MHCIIβe2 alleles called for one individual. Each genotyping strategy detected on average 50%-82% of all MHCIIβe2 alleles per individual, but dropouts were largely allele-specific and consistent within families for each strategy. The discrepancies among approaches indicate PCR biases caused by the platform-specific primer tails. Further, AmpliSAS called fewer alleles than the modified Sommer pipeline. Our results demonstrate that allelic dropout is a significant problem when genotyping the hypervariable MHCIIβe2. As these genotyping errors are largely nonrandom and method-specific, we caution against comparing genotypes across different genotyping strategies. Nevertheless, we conclude that high-throughput approaches provide a major advance in the challenging task of genotyping hypervariable MHC loci, even though they may not reveal the complete allelic repertoire.}, } @article {pmid29435242, year = {2018}, author = {Luro, AB and Igic, B and Croston, R and López, AV and Shawkey, MD and Hauber, ME}, title = {Which egg features predict egg rejection responses in American robins? Replicating Rothstein's (1982) study.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1673-1679}, pmid = {29435242}, issn = {2045-7758}, abstract = {Rothstein (Behavioral Ecology and Sociobiology, 11, 1982, 229) was one of the first comprehensive studies to examine how different egg features influence egg rejection behaviors of avian brood parasite-hosts. The methods and conclusions of Rothstein (1982) laid the foundation for subsequent experimental brood parasitism studies over the past thirty years, but its results have never been evaluated with replication. Here, we partially replicated Rothstein's (1982) experiments using parallel artificial model egg treatments to simulate cowbird (Molothrus ater) parasitism in American robin (Turdus migratorius) nests. We compared our data with those of Rothstein (1982) and confirmed most of its original findings: (1) robins reject model eggs that differ from the appearance of a natural robin egg toward that of a natural cowbird egg in background color, size, and maculation; (2) rejection responses were best predicted by model egg background color; and (3) model eggs differing by two or more features from natural robin eggs were more likely to be rejected than model eggs differing by one feature alone. In contrast with Rothstein's (1982) conclusion that American robin egg recognition is not specifically tuned toward rejection of brown-headed cowbird eggs, we argue that our results and those of other recent studies of robin egg rejection suggest a discrimination bias toward rejection of cowbird eggs. Future work on egg recognition will benefit from utilizing a range of model eggs varying continuously in background color, maculation patterning, and size in combination with avian visual modeling, rather than using model eggs which vary only discretely.}, } @article {pmid29435241, year = {2018}, author = {Guérin, M and Martin-Benito, D and von Arx, G and Andreu-Hayles, L and Griffin, KL and Hamdan, R and McDowell, NG and Muscarella, R and Pockman, W and Gentine, P}, title = {Interannual variations in needle and sapwood traits of Pinus edulis branches under an experimental drought.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1655-1672}, pmid = {29435241}, issn = {2045-7758}, abstract = {In the southwestern USA, recent large-scale die-offs of conifers raise the question of their resilience and mortality under droughts. To date, little is known about the interannual structural response to droughts. We hypothesized that piñon pines (Pinus edulis) respond to drought by reducing the drop of leaf water potential in branches from year to year through needle morphological adjustments. We tested our hypothesis using a 7-year experiment in central New Mexico with three watering treatments (irrigated, normal, and rain exclusion). We analyzed how variation in "evaporative structure" (needle length, stomatal diameter, stomatal density, stomatal conductance) responded to watering treatment and interannual climate variability. We further analyzed annual functional adjustments by comparing yearly addition of needle area (LA) with yearly addition of sapwood area (SA) and distance to tip (d), defining the yearly ratios SA:LA and SA:LA/d. Needle length (l) increased with increasing winter and monsoon water supply, and showed more interannual variability when the soil was drier. Stomatal density increased with dryness, while stomatal diameter was reduced. As a result, anatomical maximal stomatal conductance was relatively invariant across treatments. SA:LA and SA:LA/d showed significant differences across treatments and contrary to our expectation were lower with reduced water input. Within average precipitation ranges, the response of these ratios to soil moisture was similar across treatments. However, when extreme soil drought was combined with high VPD, needle length, SA:LA and SA:LA/d became highly nonlinear, emphasizing the existence of a response threshold of combined high VPD and dry soil conditions. In new branch tissues, the response of annual functional ratios to water stress was immediate (same year) and does not attempt to reduce the drop of water potential. We suggest that unfavorable evaporative structural response to drought is compensated by dynamic stomatal control to maximize photosynthesis rates.}, } @article {pmid29435240, year = {2018}, author = {Wang, Y and Rozen, DE}, title = {Gut microbiota in the burying beetle, Nicrophorus vespilloides, provide colonization resistance against larval bacterial pathogens.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1646-1654}, pmid = {29435240}, issn = {2045-7758}, abstract = {Carrion beetles, Nicrophorus vespilloides, are reared on decomposing carrion where larvae are exposed to high populations of carcass-derived bacteria. Larvae do not become colonized with these bacteria but instead are colonized with the gut microbiome of their parents, suggesting that bacteria in the beetle microbiome outcompete the carcass-derived species for larval colonization. Here, we test this hypothesis and quantify the fitness consequences of colonization with different bacterial symbionts. First, we show that beetles colonized by their endogenous microbiome produce heavier broods than those colonized with carcass-bacteria. Next, we show that bacteria from the endogenous microbiome, including Providencia rettgeri and Morganella morganii, are better colonizers of the beetle gut and can outcompete nonendogenous species, including Serratia marcescens and Escherichia coli, during in vivo competition. Finally, we find that Providencia and Morganella provide beetles with colonization resistance against Serratia and thereby reduce Serratia-induced larval mortality. This effect is eliminated in larvae first colonized by Serratia, suggesting that while competition within the larval gut is determined by priority effects, these effects are less important for Serratia-induced mortality. Our work suggests that an unappreciated benefit of parental care in N. vespilloides is the social transmission of the microbiome from parents to offspring.}, } @article {pmid29435239, year = {2018}, author = {Sargis, EJ and Millien, V and Woodman, N and Olson, LE}, title = {Rule reversal: Ecogeographical patterns of body size variation in the common treeshrew (Mammalia, Scandentia).}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1634-1645}, pmid = {29435239}, issn = {2045-7758}, abstract = {There are a number of ecogeographical "rules" that describe patterns of geographical variation among organisms. The island rule predicts that populations of larger mammals on islands evolve smaller mean body size than their mainland counterparts, whereas smaller-bodied mammals evolve larger size. Bergmann's rule predicts that populations of a species in colder climates (generally at higher latitudes) have larger mean body sizes than conspecifics in warmer climates (at lower latitudes). These two rules are rarely tested together and neither has been rigorously tested in treeshrews, a clade of small-bodied mammals in their own order (Scandentia) broadly distributed in mainland Southeast Asia and on islands throughout much of the Sunda Shelf. The common treeshrew, Tupaia glis, is an excellent candidate for study and was used to test these two rules simultaneously for the first time in treeshrews. This species is distributed on the Malay Peninsula and several offshore islands east, west, and south of the mainland. Using craniodental dimensions as a proxy for body size, we investigated how island size, distance from the mainland, and maximum sea depth between the mainland and the islands relate to body size of 13 insular T. glis populations while also controlling for latitude and correlation among variables. We found a strong negative effect of latitude on body size in the common treeshrew, indicating the inverse of Bergmann's rule. We did not detect any overall difference in body size between the island and mainland populations. However, there was an effect of island area and maximum sea depth on body size among island populations. Although there is a strong latitudinal effect on body size, neither Bergmann's rule nor the island rule applies to the common treeshrew. The results of our analyses demonstrate the necessity of assessing multiple variables simultaneously in studies of ecogeographical rules.}, } @article {pmid29435238, year = {2018}, author = {Zhang, YK and Yang, K and Zhu, YX and Hong, XY}, title = {Symbiont-conferred reproduction and fitness benefits can favour their host occurrence.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1626-1633}, pmid = {29435238}, issn = {2045-7758}, abstract = {Double infections of Wolbachia and Spiroplasma are frequent in natural populations of Tetranychus truncatus, a polyphagous mite species that has been a dominant species in China since 2009. However, little is known about the causes and ecological importance of such coexistences. In this study, we established T. truncatus strains with different infection types and then inferred the impact of the two endosymbionts on host reproduction and fitness. Double infection induced cytoplasmic incompatibility, which was demonstrated by reduction in egg hatchability of incompatible crosses. However, doubly infected females produced more eggs relative to other strains. Wolbachia and Spiroplasma did not affect host survival, whereas doubly infected females and males developed faster than other strains. Such reproduction and fitness benefits provided by double infections may be associated with the lower densities of each symbiont, and the quantitative results also confirmed competition between Wolbachia and Spiroplasma in doubly infected females. These symbiont-conferred beneficial effects maintain stable prevalence of the symbionts and also help drive T. truncatus outbreaks in combination with other environmental factors.}, } @article {pmid29435237, year = {2018}, author = {MacLeod, C and Poulin, R and Lagrue, C}, title = {Save your host, save yourself? Caste-ratio adjustment in a parasite with division of labor and snail host survival following shell damage.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1615-1625}, pmid = {29435237}, issn = {2045-7758}, abstract = {Shell damage and parasitic infections are frequent in gastropods, influencing key snail host life-history traits such as survival, growth, and reproduction. However, their interactions and potential effects on hosts and parasites have never been tested. Host-parasite interactions are particularly interesting in the context of the recently discovered division of labor in trematodes infecting marine snails. Some species have colonies consisting of two different castes present at varying ratios; reproductive members and nonreproductive soldiers specialized in defending the colony. We assessed snail host survival, growth, and shell regeneration in interaction with infections by two trematode species, Philophthalmus sp. and Maritrema novaezealandense, following damage to the shell in the New Zealand mud snail Zeacumantus subcarinatus. We concomitantly assessed caste-ratio adjustment between nonreproductive soldiers and reproductive members in colonies of the trematode Philophthalmus sp. in response to interspecific competition and shell damage to its snail host. Shell damage, but not parasitic infection, significantly increased snail mortality, likely due to secondary infections by pathogens. However, trematode infection and shell damage did not negatively affect shell regeneration or growth in Z. subcarinatus; infected snails actually produced more new shell than their uninfected counterparts. Both interspecific competition and shell damage to the snail host induced caste-ratio adjustment in Philophthalmus sp. colonies. The proportion of nonreproductive soldiers increased in response to interspecific competition and host shell damage, likely to defend the parasite colony and potentially the snail host against increasing threats. These results indicate that secondary infections by pathogens following shell damage to snails both significantly increased snail mortality and induced caste-ratio adjustments in parasites. This is the first evidence that parasites with a division of labor may be able to produce nonreproductive soldiers according to environmental factors other than interspecific competition with other parasites.}, } @article {pmid29435236, year = {2018}, author = {Thompson, NA and Cords, M}, title = {Stronger social bonds do not always predict greater longevity in a gregarious primate.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1604-1614}, pmid = {29435236}, issn = {2045-7758}, abstract = {In group-living species, individuals often have preferred affiliative social partners, with whom ties or bonds can confer advantages that correspond with greater fitness. For example, in adult female baboons and juvenile horses, individuals with stronger or more social ties experience greater survival. We used detailed behavioral and life history records to explore the relationship between tie quality and survival in a gregarious monkey (Cercopithecus mitis stuhlmanni), while controlling for dominance rank, group size, and life history strategy. We used Cox proportional hazards regressions to model the cumulative (multi-year) and current (single-year) relationships of social ties and the hazard of mortality in 83 wild adult females of known age, observed 2-8 years each (437 subject-years) in eight social groups. The strength of bonds with close partners was associated with increased mortality risk under certain conditions: Females that had strong bonds with close partners that were inconsistent over multiple years had a higher risk of mortality than females adopting any other social strategy. Within a given year, females had a higher risk of death if they were strongly bonded with partners that changed from the previous year versus with partners that remained consistent. Dominance rank, number of adult female groupmates, and age at first reproduction did not predict the risk of death. This study demonstrates that costs and benefits of strong social bonds can be context-dependent, relating to the consistency of social partners over time.}, } @article {pmid29435235, year = {2018}, author = {Spear, DM and Foster, WA and Advento, AD and Naim, M and Caliman, JP and Luke, SH and Snaddon, JL and Ps, S and Turner, EC}, title = {Simplifying understory complexity in oil palm plantations is associated with a reduction in the density of a cleptoparasitic spider, Argyrodes miniaceus (Araneae: Theridiidae), in host (Araneae: Nephilinae) webs.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1595-1603}, pmid = {29435235}, issn = {2045-7758}, abstract = {Expansion of oil palm agriculture is currently one of the main drivers of habitat modification in Southeast Asia. Habitat modification can have significant effects on biodiversity, ecosystem function, and interactions between species by altering species abundances or the available resources in an ecosystem. Increasing complexity within modified habitats has the potential to maintain biodiversity and preserve species interactions. We investigated trophic interactions between Argyrodes miniaceus, a cleptoparasitic spider, and its Nephila spp. spider hosts in mature oil palm plantations in Sumatra, Indonesia. A. miniaceus co-occupy the webs of Nephila spp. females and survive by stealing prey items caught in the web. We examined the effects of experimentally manipulated understory vegetation complexity on the density and abundance of A. miniaceus in Nephila spp. webs. Experimental understory treatments included enhanced complexity, standard complexity, and reduced complexity understory vegetation, which had been established as part of the ongoing Biodiversity and Ecosystem Function in Tropical Agriculture (BEFTA) Project. A. miniaceus density ranged from 14.4 to 31.4 spiders per square meter of web, with significantly lower densities found in reduced vegetation complexity treatments compared with both enhanced and standard treatment plots. A. miniaceus abundance per plot was also significantly lower in reduced complexity than in standard and enhanced complexity plots. Synthesis and applications: Maintenance of understory vegetation complexity contributes to the preservation of spider host-cleptoparasite relationships in oil palm plantations. Understory structural complexity in these simplified agroecosystems therefore helps to support abundant spider populations, a functionally important taxon in agricultural landscapes. In addition, management for more structurally complex agricultural habitats can support more complex trophic interactions in tropical agroecosystems.}, } @article {pmid29435234, year = {2018}, author = {Liehrmann, O and Jégoux, F and Guilbert, MA and Isselin-Nondedeu, F and Saïd, S and Locatelli, Y and Baltzinger, C}, title = {Epizoochorous dispersal by ungulates depends on fur, grooming and social interactions.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1582-1594}, pmid = {29435234}, issn = {2045-7758}, abstract = {The transport phase of the animal-mediated plant dispersal process is critical to dispersal effectiveness as it determines the spatial distribution of the diaspores released and their chance for further recruitment. Assessing this specific phase of the dispersal process generally requires combining diaspore retention times with the associated distances covered. Here, we specifically tested the effect of grooming behavior, interindividual contacts and ungulate fur on diaspore retention times and associated dispersal distances for the hooked diaspores of Xanthium strumarium L. experimentally attached to tamed individuals of three ungulate species. We used a comparative approach based on differing fur quality on different body zones of these three ungulates. During 6-hr sessions, we monitored for grooming and social interactions that may induce intended or inadvertent diaspore detachment. Additionally, we proposed innovative approaches to directly assessing diaspore dispersal distances by red deer in situ. Fat-tailed functions fitted diaspore retention time, highlighting the potential for long-distance dispersal events. The longer the hair, the higher the retention capacity of diaspores in the animal's fur. As predicted, donkey retained diaspores longer than red deer and dwarf goat; and we also confirmed that diaspores attached to the short hair of the head fell off more quickly than did those on the other body zones. Dwarf goat groomed more often than both red deer and donkey, but also when it carried diaspores. Up to 14% of the diaspores detached from animal fur after specific grooming behavior. We observed, in controlled conditions, for the first time and for each ungulate species, interindividual transfers of diaspores, representing 5% of the diaspores attached to animals' fur. Our results militate for incorporating animal behavior into plant dispersal modeling approaches.}, } @article {pmid29435233, year = {2018}, author = {Kristjánsson, BK and Leblanc, CA}, title = {Variation in the magnitude of morphological and dietary differences between individuals among populations of small benthic Arctic charr in relation to ecological factors.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1573-1581}, pmid = {29435233}, issn = {2045-7758}, abstract = {The early stages of intraspecific diversity are important for the evolution of diversification and speciation. Early stages of diversification can be seen in individual specialization, where individuals consume only a portion of the diet of the population as a whole, and how such specialization is related to phenotypic diversity within populations. Here, we study the strength of the relationship between morphological and dietary distances among individuals in eighteen populations of Icelandic small benthic charr. We furthermore studied if the strength of the relationship could be related to variation in local ecological factors these populations inhabit. In all the populations studied, there was a clear relationship between morphological and dietary distances, indicating that fish that had similar morphology were at the same time-consuming similar food items. Our findings show a systematic variation in the relationship between morphology and diet at early stages of diversification in a highly specialized small benthic charr morph. The results show the importance of fine scale comparisons within populations and furthermore the value that systematic comparisons among populations under parallel evolution can contribute toward our increased understanding of evolutionary and ecological processes.}, } @article {pmid29435232, year = {2018}, author = {Vachon, F and Whitehead, H and Frasier, TR}, title = {What factors shape genetic diversity in cetaceans?.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1554-1572}, pmid = {29435232}, issn = {2045-7758}, abstract = {Understanding what factors drive patterns of genetic diversity is a central aspect of many biological questions, ranging from the inference of historical demography to assessing the evolutionary potential of a species. However, as a larger number of datasets have become available, it is becoming clear that the relationship between the characteristics of a species and its genetic diversity is more complex than previously assumed. This may be particularly true for cetaceans, due to their relatively long lifespans, long generation times, complex social structures, and extensive ranges. In this study, we used microsatellite and mitochondrial DNA data from a systematic literature review to produce estimates of diversity for both markers across 42 cetacean species. Factors relating to demography, distribution, classification, biology, and behavior were then tested using phylogenetic methods and linear models to assess their relative influence on the genetic diversity of both marker types. The results show that while relative nuclear diversity is correlated with population size, mitochondrial diversity is not. This is particularly relevant given the widespread use of mitochondrial DNA to infer historical demography. Instead, mitochondrial diversity was mostly influenced by the range and social structure of the species. In addition to population size, habitat type (neritic vs. oceanic) had a significant correlation with relative nuclear diversity. Combined, these results show that many often-unconsidered factors are likely influencing patterns of genetic diversity in cetaceans, with implications regarding how to interpret, and what can be inferred from, existing patterns of diversity.}, } @article {pmid29435231, year = {2018}, author = {Tarekegn, GM and Tesfaye, K and Mwai, OA and Djikeng, A and Dessie, T and Birungi, J and Osama, S and Zergaw, N and Alemu, A and Achieng, G and Tutah, J and Mutai, C and Njuguna, J and Mwacharo, JM}, title = {Mitochondrial DNA variation reveals maternal origins and demographic dynamics of Ethiopian indigenous goats.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1543-1553}, pmid = {29435231}, issn = {2045-7758}, abstract = {The Horn of Africa forms one of the two main historical entry points of domestics into the continent and Ethiopia is particularly important in this regard. Through the analysis of mitochondrial DNA (mtDNA) d-loop region in 309 individuals from 13 populations, we reveal the maternal genetic variation and demographic dynamics of Ethiopian indigenous goats. A total of 174 variable sites that generated 231 haplotypes were observed. They defined two haplogroups that were present in all the 13 study populations. Reference haplotypes from the six globally defined goat mtDNA haplogroups show the two haplogroups present in Ethiopia to be A and G, the former being the most predominant. Although both haplogroups are characterized by an increase in effective population sizes (Ne) predating domestication, they also have experienced a decline in Ne at different time periods, suggesting different demographic histories. We observed seven haplotypes, six were directly linked to the central haplotypes of the two haplogroups and one was central to haplogroup G. The seven haplotypes were common between Ethiopia, Kenya, Egypt, and Saudi Arabia populations, suggesting common maternal history and the introduction of goats into East Africa via Egypt and the Arabian Peninsula, respectively. While providing new mtDNA data from a historically important region, our results suggest extensive intermixing of goats mediated by human socio-cultural and economic interactions. These have led to the coexistence of the two haplogroups in different geographic regions in Ethiopia resulting in a large caprine genetic diversity that can be exploited for genetic improvement.}, } @article {pmid29435230, year = {2018}, author = {Le Féon, V and Aubert, M and Genoud, D and Andrieu-Ponel, V and Westrich, P and Geslin, B}, title = {Range expansion of the Asian native giant resin bee Megachile sculpturalis (Hymenoptera, Apoidea, Megachilidae) in France.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1534-1542}, pmid = {29435230}, issn = {2045-7758}, abstract = {In 2008, a new species for the French bee fauna was recorded in Allauch near Marseille: the giant resin bee, Megachile sculpturalis (Smith, 1853). This was the first European record of this species that is native to East Asia. To our knowledge, it is the first introduced bee species in Europe. Here, we provide an overview of the current distribution of M. sculpturalis in France and we describe the history of its range expansion. Besides our own observations, information was compiled from literature and Internet websites, and by contacting naturalist networks. We collected a total of 117 records (locality × year combinations) for the 2008-2016 period. The geographical range of M. sculpturalis has extended remarkably, now occupying a third of continental France, with the most northern and western records located 335 and 520 km from Allauch, respectively. Information on its phenology, feeding, and nesting behavior is also provided. We report several events of nest occupation or eviction of Osmia sp. and Xylocopa sp. individuals by M. sculpturalis. Our results show that M. sculpturalis is now well established in France. Given its capacity to adapt and rapidly expand its range, we recommend amplifying the monitoring of this species to better anticipate the changes in its geographical range and its potential impacts on native bees.}, } @article {pmid29435229, year = {2018}, author = {Cannizzo, ZJ and Dixon, SR and Griffen, BD}, title = {An anthropogenic habitat within a suboptimal colonized ecosystem provides improved conditions for a range-shifting species.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1521-1533}, pmid = {29435229}, issn = {2045-7758}, abstract = {Many species are shifting their ranges in response to the changing climate. In cases where such shifts lead to the colonization of a new ecosystem, it is critical to establish how the shifting species itself is impacted by novel environmental and biological interactions. Anthropogenic habitats that are analogous to the historic habitat of a shifting species may play a crucial role in the ability of that species to expand or persist in suboptimal colonized ecosystems. We tested if the anthropogenic habitat of docks, a likely mangrove analog, provides improved conditions for the range-shifting mangrove tree crab Aratus pisonii within the colonized suboptimal salt marsh ecosystem. To test if docks provided an improved habitat, we compared the impact of the salt marsh and dock habitats on ecological and life history traits that influence the ability of this species to persist and expand into the salt marsh and compared these back to baselines in the historic mangrove ecosystem. Specifically, we examined behavior, physiology, foraging, and the thermal conditions of A. pisonii in each habitat. We found that docks provide a more favorable thermal and foraging habitat than the surrounding salt marsh, while their ability to provide conditions which improved behavior and physiology was mixed. Our study shows that anthropogenic habitats can act as analogs to historic ecosystems and enhance the habitat quality for range-shifting species in colonized suboptimal ecosystems. If the patterns that we document are general across systems, then anthropogenic habitats may play an important facilitative role in the range shifts of species with continued climate change.}, } @article {pmid29435228, year = {2018}, author = {Ganjurjav, H and Hu, G and Wan, Y and Li, Y and Danjiu, L and Gao, Q}, title = {Different responses of ecosystem carbon exchange to warming in three types of alpine grassland on the central Qinghai-Tibetan Plateau.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1507-1520}, pmid = {29435228}, issn = {2045-7758}, abstract = {Climate is a driver of terrestrial ecosystem carbon exchange, which is an important product of ecosystem function. The Qinghai-Tibetan Plateau has recently been subjected to a marked increase in temperature as a consequence of global warming. To explore the effects of warming on carbon exchange in grassland ecosystems, we conducted a whole-year warming experiment between 2012 and 2014 using open-top chambers placed in an alpine meadow, an alpine steppe, and a cultivated grassland on the central Qinghai-Tibetan Plateau. We measured the gross primary productivity, net ecosystem CO 2 exchange (NEE), ecosystem respiration, and soil respiration using a chamber-based method during the growing season. The results show that after 3 years of warming, there was significant stimulation of carbon assimilation and emission in the alpine meadow, but both these processes declined in the alpine steppe and the cultivated grassland. Under warming conditions, the soil water content was more important in stimulating ecosystem carbon exchange in the meadow and cultivated grassland than was soil temperature. In the steppe, the soil temperature was negatively correlated with ecosystem carbon exchange. We found that the ambient soil water content was significantly correlated with the magnitude of warming-induced change in NEE. Under high soil moisture condition, warming has a significant positive effect on NEE, while it has a negative effect under low soil moisture condition. Our results highlight that the NEE in steppe and cultivated grassland have negative responses to warming; after reclamation, the natural meadow would subject to loose more C in warmer condition. Therefore, under future warmer condition, the overextension of cultivated grassland should be avoided and scientific planning of cultivated grassland should be achieved.}, } @article {pmid29435227, year = {2018}, author = {Barré, K and Le Viol, I and Julliard, R and Chiron, F and Kerbiriou, C}, title = {Tillage and herbicide reduction mitigate the gap between conventional and organic farming effects on foraging activity of insectivorous bats.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1496-1506}, pmid = {29435227}, issn = {2045-7758}, abstract = {The increased use of pesticides and tillage intensification is known to negatively affect biodiversity. Changes in these agricultural practices such as herbicide and tillage reduction have variable effects among taxa, especially at the top of the trophic network including insectivorous bats. Very few studies compared the effects of agricultural practices on such taxa, and overall, only as a comparison of conventional versus organic farming without accurately accounting for underlying practices, especially in conventional where many alternatives exist. Divergent results founded in these previous studies could be driven by this lack of clarification about some unconsidered practices inside both conventional and organic systems. We simultaneously compared, over whole nights, bat activity on contiguous wheat fields of one organic and three conventional farming systems located in an intensive agricultural landscape. The studied organic fields (OT) used tillage (i.e., inversion of soil) without chemical inputs. In studied conventional fields, differences consisted of the following: tillage using few herbicides (T), conservation tillage (i.e., no inversion of soil) using few herbicides (CT), and conservation tillage using more herbicide (CTH), to control weeds. Using 64 recording sites (OT = 12; T = 21; CT = 13; CTH = 18), we sampled several sites per system placed inside the fields each night. We showed that bat activity was always higher in OT than in T systems for two (Pipistrellus kuhlii and Pipistrellus pipistrellus) of three species and for one (Pipistrellus spp.) of two genera, as well as greater species richness. The same results were found for the CT versus T system comparison. CTH system showed higher activity than T for only one genus (Pipistrellus spp.). We did not detect any differences between OT and CT systems, and CT showed higher activity than CTH system for only one species (Pipistrellus kuhlii). Activity in OT of Pipistrellus spp. was overall 3.6 and 9.3 times higher than CTH and T systems, respectively, and 6.9 times higher in CT than T systems. Our results highlight an important benefit of organic farming and contrasted effects in conventional farming. That there were no differences detected between the organic and one conventional system is a major result. This demonstrates that even if organic farming is presently difficult to implement and requires a change of economic context for farmers, considerable and easy improvements in conventional farming are attainable, while maintaining yields and approaching the ecological benefits of organic methods.}, } @article {pmid29435226, year = {2018}, author = {Schmid, S and Neuenschwander, S and Pitteloud, C and Heckel, G and Pajkovic, M and Arlettaz, R and Alvarez, N}, title = {Spatial and temporal genetic dynamics of the grasshopper Oedaleus decorus revealed by museum genomics.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1480-1495}, pmid = {29435226}, issn = {2045-7758}, abstract = {Analyzing genetic variation through time and space is important to identify key evolutionary and ecological processes in populations. However, using contemporary genetic data to infer the dynamics of genetic diversity may be at risk of a bias, as inferences are performed from a set of extant populations, setting aside unavailable, rare, or now extinct lineages. Here, we took advantage of new developments in next-generation sequencing to analyze the spatial and temporal genetic dynamics of the grasshopper Oedaleus decorus, a steppic Southwestern-Palearctic species. We applied a recently developed hybridization capture (hyRAD) protocol that allows retrieving orthologous sequences even from degraded DNA characteristic of museum specimens. We identified single nucleotide polymorphisms in 68 historical and 51 modern samples in order to (i) unravel the spatial genetic structure across part of the species distribution and (ii) assess the loss of genetic diversity over the past century in Swiss populations. Our results revealed (i) the presence of three potential glacial refugia spread across the European continent and converging spatially in the Alpine area. In addition, and despite a limited population sample size, our results indicate (ii) a loss of allelic richness in contemporary Swiss populations compared to historical populations, whereas levels of expected heterozygosities were not significantly different. This observation is compatible with an increase in the bottleneck magnitude experienced by central European populations of O. decorus following human-mediated land-use change impacting steppic habitats. Our results confirm that application of hyRAD to museum samples produces valuable information to study genetic processes across time and space.}, } @article {pmid29435225, year = {2018}, author = {Martins, RF and Schmidt, A and Lenz, D and Wilting, A and Fickel, J}, title = {Human-mediated introduction of introgressed deer across Wallace's line: Historical biogeography of Rusa unicolor and R. timorensis.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1465-1479}, pmid = {29435225}, issn = {2045-7758}, abstract = {In this study we compared the phylogeographic patterns of two Rusa species, Rusa unicolor and Rusa timorensis, in order to understand what drove and maintained differentiation between these two geographically and genetically close species and investigated the route of introduction of individuals to the islands outside of the Sunda Shelf. We analyzed full mitogenomes from 56 archival samples from the distribution areas of the two species and 18 microsatellite loci in a subset of 16 individuals to generate the phylogeographic patterns of both species. Bayesian inference with fossil calibration was used to estimate the age of each species and major divergence events. Our results indicated that the split between the two species took place during the Pleistocene, ~1.8 Mya, possibly driven by adaptations of R. timorensis to the drier climate found on Java compared to the other islands of Sundaland. Although both markers identified two well-differentiated clades, there was a largely discrepant pattern between mitochondrial and nuclear markers. While nDNA separated the individuals into the two species, largely in agreement with their museum label, mtDNA revealed that all R. timorensis sampled to the east of the Sunda shelf carried haplotypes from R. unicolor and one Rusa unicolor from South Sumatra carried a R. timorensis haplotype. Our results show that hybridization occurred between these two sister species in Sundaland during the Late Pleistocene and resulted in human-mediated introduction of hybrid descendants in all islands outside Sundaland.}, } @article {pmid29435224, year = {2018}, author = {Montiglio, PO and McGlothlin, JW and Farine, DR}, title = {Social structure modulates the evolutionary consequences of social plasticity: A social network perspective on interacting phenotypes.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1451-1464}, pmid = {29435224}, issn = {2045-7758}, abstract = {Organisms express phenotypic plasticity during social interactions. Interacting phenotype theory has explored the consequences of social plasticity for evolution, but it is unclear how this theory applies to complex social structures. We adapt interacting phenotype models to general social structures to explore how the number of social connections between individuals and preference for phenotypically similar social partners affect phenotypic variation and evolution. We derive an analytical model that ignores phenotypic feedback and use simulations to test the predictions of this model. We find that adapting previous models to more general social structures does not alter their general conclusions but generates insights into the effect of social plasticity and social structure on the maintenance of phenotypic variation and evolution. Contribution of indirect genetic effects to phenotypic variance is highest when interactions occur at intermediate densities and decrease at higher densities, when individuals approach interacting with all group members, homogenizing the social environment across individuals. However, evolutionary response to selection tends to increase at greater network densities as the effects of an individual's genes are amplified through increasing effects on other group members. Preferential associations among similar individuals (homophily) increase both phenotypic variance within groups and evolutionary response to selection. Our results represent a first step in relating social network structure to the expression of social plasticity and evolutionary responses to selection.}, } @article {pmid29435223, year = {2018}, author = {Boyle, JH and Martins, DJ and Pelaez, J and Musili, PM and Kibet, S and Ndung'u, SK and Kenfack, D and Pierce, NE}, title = {Polygyny does not explain the superior competitive ability of dominant ant associates in the African ant-plant, Acacia (Vachellia) drepanolobium.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1441-1450}, pmid = {29435223}, issn = {2045-7758}, abstract = {The Acacia drepanolobium (also known as Vachellia drepanolobium) ant-plant symbiosis is considered a classic case of species coexistence, in which four species of tree-defending ants compete for nesting space in a single host tree species. Coexistence in this system has been explained by trade-offs in the ability of the ant associates to compete with each other for occupied trees versus the ability to colonize unoccupied trees. We seek to understand the proximal reasons for how and why the ant species vary in competitive or colonizing abilities, which are largely unknown. In this study, we use RADseq-derived SNPs to identify relatedness of workers in colonies to test the hypothesis that competitively dominant ants reach large colony sizes due to polygyny, that is, the presence of multiple egg-laying queens in a single colony. We find that variation in polygyny is not associated with competitive ability; in fact, the most dominant species, unexpectedly, showed little evidence of polygyny. We also use these markers to investigate variation in mating behavior among the ant species and find that different species vary in the number of males fathering the offspring of each colony. Finally, we show that the nature of polygyny varies between the two commonly polygynous species, Crematogaster mimosae and Tetraponera penzigi: in C. mimosae, queens in the same colony are often related, while this is not the case for T. penzigi. These results shed light on factors influencing the evolution of species coexistence in an ant-plant mutualism, as well as demonstrating the effectiveness of RADseq-derived SNPs for parentage analysis.}, } @article {pmid29435222, year = {2018}, author = {Nunes, KA and Kotanen, PM}, title = {Comparative impacts of aboveground and belowground enemies on an invasive thistle.}, journal = {Ecology and evolution}, volume = {8}, number = {3}, pages = {1430-1440}, pmid = {29435222}, issn = {2045-7758}, abstract = {Most research examining how herbivores and pathogens affect performance of invasive plants focuses on aboveground interactions. Although important, the role of belowground communities remains poorly understood, and the relative impact of aboveground and belowground interactions is still debated. As well, most studies of belowground interactions have been carried out in controlled environments, so little is known about the role of these interactions under natural conditions or how these relationships may change across a plant's range. Using the invasive plant Cirsium arvense, we performed a reciprocal transplant experiment to test the relative impacts of above- and belowground interactions at three sites across a 509-km latitudinal gradient in its invaded range in Ontario, Canada. At each site, C. arvense seedlings were protected with above- and/or belowground exclosures in a factorial design. Plant performance (biomass, height, stem thickness, number of leaves, length of longest leaf, maximum rhizome length) was greatest when both above- and belowground exclosures were applied and lowest when no exclosures were applied. When only one type of exclosure was applied, biomass generally improved more with belowground exclosures than with aboveground exclosures. Despite site-to-site differences in foliar damage, root damage, and mesofaunal populations, belowground interactions generally had a greater negative impact on performance than aboveground herbivory alone. These results stress the importance of including both aboveground enemy interactions and plant-soil interactions in studies of plant community dynamics and invader performance.}, } @article {pmid29435100, year = {2018}, author = {Ridl, J and Suman, J and Fraraccio, S and Hradilova, M and Strejcek, M and Cajthaml, T and Zubrova, A and Macek, T and Strnad, H and Uhlik, O}, title = {Complete genome sequence of Pseudomonas alcaliphila JAB1 (=DSM 26533), a versatile degrader of organic pollutants.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {3}, pmid = {29435100}, issn = {1944-3277}, abstract = {In this study, following its isolation from contaminated soil, the genomic sequence of Pseudomonas alcaliphila strain JAB1 (=DSM 26533), a biphenyl-degrading bacterium, is reported and analyzed in relation to its extensive degradative capabilities. The P. alcaliphila JAB1 genome (GenBank accession no. CP016162) consists of a single 5.34 Mbp-long chromosome with a GC content of 62.5%. Gene function was assigned to 3816 of the 4908 predicted genes. The genome harbors a bph gene cluster, permitting degradation of biphenyl and many congeners of polychlorinated biphenyls (PCBs), a ben gene cluster, enabling benzoate and its derivatives to be degraded, and phe gene cluster, which permits phenol degradation. In addition, P. alcaliphila JAB1 is capable of cometabolically degrading cis-1,2-dichloroethylene (cDCE) when grown on phenol. The strain carries both catechol and protocatechuate branches of the β-ketoadipate pathway, which is used to funnel the pollutants to the central metabolism. Furthermore, we propose that clustering of MALDI-TOF MS spectra with closest phylogenetic relatives should be used when taxonomically classifying the isolated bacterium; this, together with 16S rRNA gene sequence and chemotaxonomic data analyses, enables more precise identification of the culture at the species level.}, } @article {pmid29434356, year = {2018}, author = {Kema, GHJ and Mirzadi Gohari, A and Aouini, L and Gibriel, HAY and Ware, SB and van den Bosch, F and Manning-Smith, R and Alonso-Chavez, V and Helps, J and Ben M'Barek, S and Mehrabi, R and Diaz-Trujillo, C and Zamani, E and Schouten, HJ and van der Lee, TAJ and Waalwijk, C and de Waard, MA and de Wit, PJGM and Verstappen, ECP and Thomma, BPHJ and Meijer, HJG and Seidl, MF}, title = {Stress and sexual reproduction affect the dynamics of the wheat pathogen effector AvrStb6 and strobilurin resistance.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {375-380}, doi = {10.1038/s41588-018-0052-9}, pmid = {29434356}, issn = {1546-1718}, abstract = {Host resistance and fungicide treatments are cornerstones of plant-disease control. Here, we show that these treatments allow sex and modulate parenthood in the fungal wheat pathogen Zymoseptoria tritici. We demonstrate that the Z. tritici-wheat interaction complies with the gene-for-gene model by identifying the effector AvrStb6, which is recognized by the wheat resistance protein Stb6. Recognition triggers host resistance, thus implying removal of avirulent strains from pathogen populations. However, Z. tritici crosses on wheat show that sex occurs even with an avirulent parent, and avirulence alleles are thereby retained in subsequent populations. Crossing fungicide-sensitive and fungicide-resistant isolates under fungicide pressure results in a rapid increase in resistance-allele frequency. Isolates under selection always act as male donors, and thus disease control modulates parenthood. Modeling these observations for agricultural and natural environments reveals extended durability of host resistance and rapid emergence of fungicide resistance. Therefore, fungal sex has major implications for disease control.}, } @article {pmid29434355, year = {2018}, author = {Saintenac, C and Lee, WS and Cambon, F and Rudd, JJ and King, RC and Marande, W and Powers, SJ and Bergès, H and Phillips, AL and Uauy, C and Hammond-Kosack, KE and Langin, T and Kanyuka, K}, title = {Wheat receptor-kinase-like protein Stb6 controls gene-for-gene resistance to fungal pathogen Zymoseptoria tritici.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {368-374}, doi = {10.1038/s41588-018-0051-x}, pmid = {29434355}, issn = {1546-1718}, support = {BB/I000712/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Deployment of fast-evolving disease-resistance genes is one of the most successful strategies used by plants to fend off pathogens1,2. In gene-for-gene relationships, most cloned disease-resistance genes encode intracellular nucleotide-binding leucine-rich-repeat proteins (NLRs) recognizing pathogen-secreted isolate-specific avirulence (Avr) effectors delivered to the host cytoplasm3,4. This process often triggers a localized hypersensitive response, which halts further disease development 5 . Here we report the map-based cloning of the wheat Stb6 gene and demonstrate that it encodes a conserved wall-associated receptor kinase (WAK)-like protein, which detects the presence of a matching apoplastic effector6-8 and confers pathogen resistance without a hypersensitive response 9 . This report demonstrates gene-for-gene disease resistance controlled by this class of proteins in plants. Moreover, Stb6 is, to our knowledge, the first cloned gene specifying resistance to Zymoseptoria tritici, an important foliar fungal pathogen affecting wheat and causing economically damaging septoria tritici blotch (STB) disease10-12.}, } @article {pmid29434352, year = {2018}, author = {Samani, P and Reuter, M}, title = {Genomic health in an asexual fish.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {595-596}, doi = {10.1038/s41559-018-0485-7}, pmid = {29434352}, issn = {2397-334X}, } @article {pmid29434351, year = {2018}, author = {Warren, WC and García-Pérez, R and Xu, S and Lampert, KP and Chalopin, D and Stöck, M and Loewe, L and Lu, Y and Kuderna, L and Minx, P and Montague, MJ and Tomlinson, C and Hillier, LW and Murphy, DN and Wang, J and Wang, Z and Garcia, CM and Thomas, GCW and Volff, JN and Farias, F and Aken, B and Walter, RB and Pruitt, KD and Marques-Bonet, T and Hahn, MW and Kneitz, S and Lynch, M and Schartl, M}, title = {Clonal polymorphism and high heterozygosity in the celibate genome of the Amazon molly.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {669-679}, pmid = {29434351}, issn = {2397-334X}, support = {//Wellcome Trust/United Kingdom ; R24 OD011120/OD/NIH HHS/United States ; R24 OD011198/OD/NIH HHS/United States ; R24 RR032658/RR/NCRR NIH HHS/United States ; }, abstract = {The extreme rarity of asexual vertebrates in nature is generally explained by genomic decay due to absence of meiotic recombination, thus leading to extinction of such lineages. We explore features of a vertebrate asexual genome, the Amazon molly, Poecilia formosa, and find few signs of genetic degeneration but unique genetic variability and ongoing evolution. We uncovered a substantial clonal polymorphism and, as a conserved feature from its interspecific hybrid origin, a 10-fold higher heterozygosity than in the sexual parental species. These characteristics seem to be a principal reason for the unpredicted fitness of this asexual vertebrate. Our data suggest that asexual vertebrate lineages are scarce not because they are at a disadvantage, but because the genomic combinations required to bypass meiosis and to make up a functioning hybrid genome are rarely met in nature.}, } @article {pmid29434350, year = {2018}, author = {Hicks, HL and Comont, D and Coutts, SR and Crook, L and Hull, R and Norris, K and Neve, P and Childs, DZ and Freckleton, RP}, title = {The factors driving evolved herbicide resistance at a national scale.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {529-536}, doi = {10.1038/s41559-018-0470-1}, pmid = {29434350}, issn = {2397-334X}, abstract = {Repeated use of xenobiotic chemicals has selected for the rapid evolution of resistance, threatening health and food security at a global scale. Strategies for preventing the evolution of resistance include cycling and mixtures of chemicals and diversification of management. We currently lack large-scale studies that evaluate the efficacy of these different strategies for minimizing the evolution of resistance. Here we use a national-scale data set of occurrence of the weed Alopecurus myosuroides (black-grass) in the United Kingdom to address this. Weed densities are correlated with assays of evolved resistance, supporting the hypothesis that resistance is driving weed abundance at a national scale. Resistance was correlated with the frequency of historical herbicide applications, suggesting that evolution of resistance is primarily driven by intensity of exposure to herbicides, but was unrelated directly to other cultural techniques. We find that populations resistant to one herbicide are likely to show resistance to multiple herbicide classes. Finally, we show that the economic costs of evolved resistance are considerable: loss of control through resistance can double the economic costs of weeds. This research highlights the importance of managing threats to food production and healthcare systems using an evolutionarily informed approach in a proactive not reactive manner.}, } @article {pmid29434349, year = {2018}, author = {Bengston, SE and Dahan, RA and Donaldson, Z and Phelps, SM and van Oers, K and Sih, A and Bell, AM}, title = {Genomic tools for behavioural ecologists to understand repeatable individual differences in behaviour.}, journal = {Nature ecology & evolution}, volume = {2}, number = {6}, pages = {944-955}, doi = {10.1038/s41559-017-0411-4}, pmid = {29434349}, issn = {2397-334X}, abstract = {Behaviour is a key interface between an animal's genome and its environment. Repeatable individual differences in behaviour have been extensively documented in animals, but the molecular underpinnings of behavioural variation among individuals within natural populations remain largely unknown. Here, we offer a critical review of when molecular techniques may yield new insights, and we provide specific guidance on how and whether the latest tools available are appropriate given different resources, system and organismal constraints, and experimental designs. Integrating molecular genetic techniques with other strategies to study the proximal causes of behaviour provides opportunities to expand rapidly into new avenues of exploration. Such endeavours will enable us to better understand how repeatable individual differences in behaviour have evolved, how they are expressed and how they can be maintained within natural populations of animals.}, } @article {pmid29434348, year = {2018}, author = {Bach, LT and Lohbeck, KT and Reusch, TBH and Riebesell, U}, title = {Rapid evolution of highly variable competitive abilities in a key phytoplankton species.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {611-613}, doi = {10.1038/s41559-018-0474-x}, pmid = {29434348}, issn = {2397-334X}, abstract = {Climate change challenges plankton communities, but evolutionary adaptation could mitigate the potential impacts. Here, we tested with the phytoplankton species Emiliania huxleyi whether adaptation to a stressor under laboratory conditions leads to equivalent fitness gains in a more natural environment. We found that fitness advantages that had evolved under laboratory conditions were masked by pleiotropic effects in natural plankton communities. Moreover, new genotypes with highly variable competitive abilities evolved on timescales significantly shorter than climate change.}, } @article {pmid29434326, year = {2018}, author = {Hover, BM and Kim, SH and Katz, M and Charlop-Powers, Z and Owen, JG and Ternei, MA and Maniko, J and Estrela, AB and Molina, H and Park, S and Perlin, DS and Brady, SF}, title = {Culture-independent discovery of the malacidins as calcium-dependent antibiotics with activity against multidrug-resistant Gram-positive pathogens.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {415-422}, pmid = {29434326}, issn = {2058-5276}, support = {U19 AI109713/AI/NIAID NIH HHS/United States ; U01 GM110714/GM/NIGMS NIH HHS/United States ; F32 AI124479/AI/NIAID NIH HHS/United States ; F32 AI110029/AI/NIAID NIH HHS/United States ; R35 GM122559/GM/NIGMS NIH HHS/United States ; }, abstract = {Despite the wide availability of antibiotics, infectious diseases remain a leading cause of death worldwide 1 . In the absence of new therapies, mortality rates due to untreatable infections are predicted to rise more than tenfold by 2050. Natural products (NPs) made by cultured bacteria have been a major source of clinically useful antibiotics. In spite of decades of productivity, the use of bacteria in the search for new antibiotics was largely abandoned due to high rediscovery rates2,3. As only a fraction of bacterial diversity is regularly cultivated in the laboratory and just a fraction of the chemistries encoded by cultured bacteria are detected in fermentation experiments, most bacterial NPs remain hidden in the global microbiome. In an effort to access these hidden NPs, we have developed a culture-independent NP discovery platform that involves sequencing, bioinformatic analysis and heterologous expression of biosynthetic gene clusters captured on DNA extracted from environmental samples. Here, we describe the application of this platform to the discovery of the malacidins, a distinctive class of antibiotics that are commonly encoded in soil microbiomes but have never been reported in culture-based NP discovery efforts. The malacidins are active against multidrug-resistant pathogens, sterilize methicillin-resistant Staphylococcus aureus skin infections in an animal wound model and did not select for resistance under our laboratory conditions.}, } @article {pmid29434049, year = {2018}, author = {Caginalp, C and Caginalp, G}, title = {Opinion: Valuation, liquidity price, and stability of cryptocurrencies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1131-1134}, pmid = {29434049}, issn = {1091-6490}, } @article {pmid29434045, year = {2018}, author = {Bennett, KE and Jagsi, R and Zietman, A}, title = {Radiation oncology authors and reviewers prefer double-blind peer review.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1940}, pmid = {29434045}, issn = {1091-6490}, mesh = {*Double-Blind Method ; Peer Review ; Peer Review, Research ; Periodicals as Topic ; *Radiation Oncology ; }, } @article {pmid29434044, year = {2018}, author = {Tomkins, A and Heavlin, WD and Zhang, M}, title = {Reply to Bennett et al.: IJROBP study is consistent with our findings and offers insights on author preferences.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {E1941}, pmid = {29434044}, issn = {1091-6490}, mesh = {*Peer Review, Research ; }, } @article {pmid29434043, year = {2018}, author = {Anderson, A and Green, EA}, title = {Personal bests as reference points.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1772-1776}, pmid = {29434043}, issn = {1091-6490}, mesh = {*Achievement ; Algorithms ; Female ; Goals ; Humans ; Male ; Models, Statistical ; Motivation ; Video Games/*psychology ; }, abstract = {Personal bests act as reference points. Examining 133 million chess games, we find that players exert effort to set new personal best ratings and quit once they have done so. Although specific and difficult goals have been shown to inspire greater motivation than vague pronouncements to "do your best," doing one's best can be a specific and difficult goal-and, as we show, motivates in a manner predicted by loss aversion.}, } @article {pmid29434042, year = {2018}, author = {Mattingly, HH and Transtrum, MK and Abbott, MC and Machta, BB}, title = {Maximizing the information learned from finite data selects a simple model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1760-1765}, pmid = {29434042}, issn = {1091-6490}, support = {R01 GM107103/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Bayes Theorem ; *Models, Statistical ; }, abstract = {We use the language of uninformative Bayesian prior choice to study the selection of appropriately simple effective models. We advocate for the prior which maximizes the mutual information between parameters and predictions, learning as much as possible from limited data. When many parameters are poorly constrained by the available data, we find that this prior puts weight only on boundaries of the parameter space. Thus, it selects a lower-dimensional effective theory in a principled way, ignoring irrelevant parameter directions. In the limit where there are sufficient data to tightly constrain any number of parameters, this reduces to the Jeffreys prior. However, we argue that this limit is pathological when applied to the hyperribbon parameter manifolds generic in science, because it leads to dramatic dependence on effects invisible to experiment.}, } @article {pmid29434041, year = {2018}, author = {Kawakami, M and Mustachio, LM and Zheng, L and Chen, Y and Rodriguez-Canales, J and Mino, B and Kurie, JM and Roszik, J and Villalobos, PA and Thu, KL and Silvester, J and Cescon, DW and Wistuba, II and Mak, TW and Liu, X and Dmitrovsky, E}, title = {Polo-like kinase 4 inhibition produces polyploidy and apoptotic death of lung cancers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1913-1918}, pmid = {29434041}, issn = {1091-6490}, support = {R01 CA087546/CA/NCI NIH HHS/United States ; R01 CA190722/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/pharmacology/therapeutic use ; Apoptosis/*drug effects ; Cell Line, Tumor ; Centrosome ; Gene Expression Regulation, Neoplastic ; Humans ; Indazoles/*pharmacology/therapeutic use ; Indoles/*pharmacology/therapeutic use ; Mice ; Neoplasms, Experimental/drug therapy/metabolism ; *Polyploidy ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors ; }, abstract = {Polo-like kinase 4 (PLK4) is a serine/threonine kinase regulating centriole duplication. CFI-400945 is a highly selective PLK4 inhibitor that deregulates centriole duplication, causing mitotic defects and death of aneuploid cancers. Prior work was substantially extended by showing CFI-400945 causes polyploidy, growth inhibition, and apoptotic death of murine and human lung cancer cells, despite expression of mutated KRAS or p53. Analysis of DNA content by propidium iodide (PI) staining revealed cells with >4N DNA content (polyploidy) markedly increased after CFI-400945 treatment. Centrosome numbers and mitotic spindles were scored. CFI-400945 treatment produced supernumerary centrosomes and mitotic defects in lung cancer cells. In vivo antineoplastic activity of CFI-400945 was established in mice with syngeneic lung cancer xenografts. Lung tumor growth was significantly inhibited at well-tolerated dosages. Phosphohistone H3 staining of resected lung cancers following CFI-400945 treatment confirmed the presence of aberrant mitosis. PLK4 expression profiles in human lung cancers were explored using The Cancer Genome Atlas (TCGA) and RNA in situ hybridization (RNA ISH) of microarrays containing normal and malignant lung tissues. PLK4 expression was significantly higher in the malignant versus normal lung and conferred an unfavorable survival (P < 0.05). Intriguingly, cyclin dependent kinase 2 (CDK2) antagonism cooperated with PLK4 inhibition. Taken together, PLK4 inhibition alone or as part of a combination regimen is a promising way to combat lung cancer.}, } @article {pmid29434040, year = {2018}, author = {Rawson, S and Bisson, C and Hurdiss, DL and Fazal, A and McPhillie, MJ and Sedelnikova, SE and Baker, PJ and Rice, DW and Muench, SP}, title = {Elucidating the structural basis for differing enzyme inhibitor potency by cryo-EM.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1795-1800}, pmid = {29434040}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; G1000567//Medical Research Council/United Kingdom ; 009752/Z/12/Z//Wellcome Trust/United Kingdom ; 102572/B/13/Z//Wellcome Trust/United Kingdom ; BB/I003703/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 108466/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Arabidopsis/chemistry/drug effects/*enzymology/ultrastructure ; Arabidopsis Proteins/*antagonists & inhibitors/chemistry/ultrastructure ; Binding Sites ; Cryoelectron Microscopy ; Crystallography, X-Ray ; Enzyme Inhibitors/*chemistry ; Herbicides/chemistry ; Hydro-Lyases/*antagonists & inhibitors/chemistry/ultrastructure ; Models, Molecular ; Saccharomyces cerevisiae/chemistry/drug effects/*enzymology/ultrastructure ; Saccharomyces cerevisiae Proteins/*antagonists & inhibitors/chemistry/ultrastructure ; }, abstract = {Histidine biosynthesis is an essential process in plants and microorganisms, making it an attractive target for the development of herbicides and antibacterial agents. Imidazoleglycerol-phosphate dehydratase (IGPD), a key enzyme within this pathway, has been biochemically characterized in both Saccharomyces cerevisiae (Sc_IGPD) and Arabidopsis thaliana (At_IGPD). The plant enzyme, having been the focus of in-depth structural analysis as part of an inhibitor development program, has revealed details about the reaction mechanism of IGPD, whereas the yeast enzyme has proven intractable to crystallography studies. The structure-activity relationship of potent triazole-phosphonate inhibitors of IGPD has been determined in both homologs, revealing that the lead inhibitor (C348) is an order of magnitude more potent against Sc_IGPD than At_IGPD; however, the molecular basis of this difference has not been established. Here we have used single-particle electron microscopy (EM) to study structural differences between the At and Sc_IGPD homologs, which could influence the difference in inhibitor potency. The resulting EM maps at ∼3 Å are sufficient to de novo build the protein structure and identify the inhibitor binding site, which has been validated against the crystal structure of the At_IGPD/C348 complex. The structure of Sc_IGPD reveals that a 24-amino acid insertion forms an extended loop region on the enzyme surface that lies adjacent to the active site, forming interactions with the substrate/inhibitor binding loop that may influence inhibitor potency. Overall, this study provides insights into the IGPD family and demonstrates the power of using an EM approach to study inhibitor binding.}, } @article {pmid29434039, year = {2018}, author = {Hoffmann, A and Käser, S and Jakob, M and Amodeo, S and Peitsch, C and Týč, J and Vaughan, S and Zuber, B and Schneider, A and Ochsenreiter, T}, title = {Molecular model of the mitochondrial genome segregation machinery in Trypanosoma brucei.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1809-E1818}, pmid = {29434039}, issn = {1091-6490}, support = {BB/L014122/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {DNA, Kinetoplast/genetics ; Gene Expression Regulation/*physiology ; Genome, Mitochondrial/*physiology ; Genome, Protozoan/*physiology ; Models, Biological ; Trypanosoma brucei brucei/*genetics ; }, abstract = {In almost all eukaryotes, mitochondria maintain their own genome. Despite the discovery more than 50 y ago, still very little is known about how the genome is correctly segregated during cell division. The protozoan parasite Trypanosoma brucei contains a single mitochondrion with a singular genome, the kinetoplast DNA (kDNA). Electron microscopy studies revealed the tripartite attachment complex (TAC) to physically connect the kDNA to the basal body of the flagellum and to ensure correct segregation of the mitochondrial genome via the basal bodies movement, during the cell cycle. Using superresolution microscopy, we precisely localize each of the currently known TAC components. We demonstrate that the TAC is assembled in a hierarchical order from the base of the flagellum toward the mitochondrial genome and that the assembly is not dependent on the kDNA itself. Based on the biochemical analysis, the TAC consists of several nonoverlapping subcomplexes, suggesting an overall size of the TAC exceeding 2.8 mDa. We furthermore demonstrate that the TAC is required for correct mitochondrial organelle positioning but not for organelle biogenesis or segregation.}, } @article {pmid29434038, year = {2018}, author = {Paredes, F and Sheldon, K and Lassègue, B and Williams, HC and Faidley, EA and Benavides, GA and Torres, G and Sanhueza-Olivares, F and Yeligar, SM and Griendling, KK and Darley-Usmar, V and San Martin, A}, title = {Poldip2 is an oxygen-sensitive protein that controls PDH and αKGDH lipoylation and activation to support metabolic adaptation in hypoxia and cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1789-1794}, pmid = {29434038}, issn = {1091-6490}, support = {R00 AA021803/AA/NIAAA NIH HHS/United States ; T32 HL007745/HL/NHLBI NIH HHS/United States ; P01 HL095070/HL/NHLBI NIH HHS/United States ; UL1 TR000454/TR/NCATS NIH HHS/United States ; R01 HL113167/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Coenzyme A Ligases/genetics/metabolism ; Humans ; Hypoxia/*enzymology/genetics/metabolism ; Ketoglutarate Dehydrogenase Complex/genetics/metabolism ; Lipoylation ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mitochondria/enzymology/genetics/metabolism ; Mitochondrial Proteins/genetics/metabolism ; Neoplasms/*enzymology/genetics/metabolism ; Nuclear Proteins/genetics/*metabolism ; Oxygen/*metabolism ; Protein-Serine-Threonine Kinases/genetics/metabolism ; Thioctic Acid/metabolism ; }, abstract = {Although the addition of the prosthetic group lipoate is essential to the activity of critical mitochondrial catabolic enzymes, its regulation is unknown. Here, we show that lipoylation of the pyruvate dehydrogenase and α-ketoglutarate dehydrogenase (αKDH) complexes is a dynamically regulated process that is inhibited under hypoxia and in cancer cells to restrain mitochondrial respiration. Mechanistically, we found that the polymerase-δ interacting protein 2 (Poldip2), a nuclear-encoded mitochondrial protein of unknown function, controls the lipoylation of the pyruvate and α-KDH dihydrolipoamide acetyltransferase subunits by a mechanism that involves regulation of the caseinolytic peptidase (Clp)-protease complex and degradation of the lipoate-activating enzyme Ac-CoA synthetase medium-chain family member 1 (ACSM1). ACSM1 is required for the utilization of lipoic acid derived from a salvage pathway, an unacknowledged lipoylation mechanism. In Poldip2-deficient cells, reduced lipoylation represses mitochondrial function and induces the stabilization of hypoxia-inducible factor 1α (HIF-1α) by loss of substrate inhibition of prolyl-4-hydroxylases (PHDs). HIF-1α-mediated retrograde signaling results in a metabolic reprogramming that resembles hypoxic and cancer cell adaptation. Indeed, we observe that Poldip2 expression is down-regulated by hypoxia in a variety of cell types and basally repressed in triple-negative cancer cells, leading to inhibition of lipoylation of the pyruvate and α-KDH complexes and mitochondrial dysfunction. Increasing mitochondrial lipoylation by forced expression of Poldip2 increases respiration and reduces the growth rate of cancer cells. Our work unveils a regulatory mechanism of catabolic enzymes required for metabolic plasticity and highlights the role of Poldip2 as key during hypoxia and cancer cell metabolic adaptation.}, } @article {pmid29434037, year = {2018}, author = {Qu, Z and Temel, FZ and Henderikx, R and Breuer, KS}, title = {Changes in the flagellar bundling time account for variations in swimming behavior of flagellated bacteria in viscous media.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1707-1712}, pmid = {29434037}, issn = {1091-6490}, mesh = {Escherichia coli/chemistry/*cytology/genetics/physiology ; Flagella/chemistry/*physiology ; Kinetics ; Models, Biological ; Rotation ; }, abstract = {Although the motility of the flagellated bacteria, Escherichia coli, has been widely studied, the effect of viscosity on swimming speed remains controversial. The swimming mode of wild-type E. coli is often idealized as a run-and-tumble sequence in which periods of swimming at a constant speed are randomly interrupted by a sudden change of direction at a very low speed. Using a tracking microscope, we follow cells for extended periods of time in Newtonian liquids of varying viscosity and find that the swimming behavior of a single cell can exhibit a variety of behaviors, including run and tumble and "slow random walk" in which the cells move at a relatively low speed. Although the characteristic swimming speed varies between individuals and in different polymer solutions, we find that the skewness of the speed distribution is solely a function of viscosity and can be used, in concert with the measured average swimming speed, to determine the effective running speed of each cell. We hypothesize that differences in the swimming behavior observed in solutions of different viscosity are due to changes in the flagellar bundling time, which increases as the viscosity rises, due to the lower rotation rate of the flagellar motor. A numerical simulation and the use of resistive force theory provide support for this hypothesis.}, } @article {pmid29434036, year = {2018}, author = {Buja, A and Volfovsky, N and Krieger, AM and Lord, C and Lash, AE and Wigler, M and Iossifov, I}, title = {Damaging de novo mutations diminish motor skills in children on the autism spectrum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1859-E1866}, pmid = {29434036}, issn = {1091-6490}, mesh = {Autism Spectrum Disorder/*genetics ; Child ; Female ; Genotype ; Humans ; Male ; Motor Skills/*physiology ; Mutation ; }, abstract = {In individuals with autism spectrum disorder (ASD), de novo mutations have previously been shown to be significantly correlated with lower IQ but not with the core characteristics of ASD: deficits in social communication and interaction and restricted interests and repetitive patterns of behavior. We extend these findings by demonstrating in the Simons Simplex Collection that damaging de novo mutations in ASD individuals are also significantly and convincingly correlated with measures of impaired motor skills. This correlation is not explained by a correlation between IQ and motor skills. We find that IQ and motor skills are distinctly associated with damaging mutations and, in particular, that motor skills are a more sensitive indicator of mutational severity than is IQ, as judged by mutational type and target gene. We use this finding to propose a combined classification of phenotypic severity: mild (little impairment of either), moderate (impairment mainly to motor skills), and severe (impairment of both IQ and motor skills).}, } @article {pmid29433813, year = {2018}, author = {Day, TA and Kimber, MJ}, title = {Praziquantel Interaction with Mammalian Targets in the Spotlight.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {263-265}, doi = {10.1016/j.pt.2018.01.006}, pmid = {29433813}, issn = {1471-5007}, mesh = {Animals ; Humans ; Mice ; *Praziquantel ; *Schistosomicides ; }, abstract = {Chan et al. recently demonstrated that the antischistosomal drug praziquantel has a potent and specific interaction with human 5-HT2B receptors, and that the drug also elicits contraction of mouse mesenteric vasculature apparently mediated by the same receptor subtype We consider what this might mean about the drug's molecular therapeutic targets in both the worm and the host.}, } @article {pmid29433762, year = {2018}, author = {}, title = {What Genetic Concept(s) Do You Think Are the Hardest for the Students to Grasp?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {162-164}, doi = {10.1016/j.tig.2018.01.007}, pmid = {29433762}, issn = {0168-9525}, mesh = {Gene Expression Regulation ; Genetic Diseases, Inborn/genetics ; *Genetic Phenomena ; Genetics/*education ; Humans ; *Learning ; Molecular Biology ; Mutation ; Students/*psychology ; Teaching/psychology ; }, } @article {pmid29433761, year = {2018}, author = {}, title = {What Aspect(s) of Genetics do You Think Most Excites Students in Your Classes?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {159-161}, doi = {10.1016/j.tig.2018.01.005}, pmid = {29433761}, issn = {0168-9525}, mesh = {*Genetic Phenomena ; *Genetic Techniques ; Genetics/*education ; Humans ; Motivation ; Students/*psychology ; Teaching/psychology ; }, } @article {pmid29433554, year = {2018}, author = {Cregger, MA and Veach, AM and Yang, ZK and Crouch, MJ and Vilgalys, R and Tuskan, GA and Schadt, CW}, title = {The Populus holobiont: dissecting the effects of plant niches and genotype on the microbiome.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {31}, pmid = {29433554}, issn = {2049-2618}, mesh = {Archaea/*classification/genetics/isolation & purification ; Bacteria/*classification/genetics/isolation & purification ; DNA, Ribosomal/genetics ; Fungi/*classification/genetics/isolation & purification ; Genotype ; High-Throughput Nucleotide Sequencing/*methods ; Microbiota ; Organ Specificity ; Plant Leaves/microbiology ; Plant Roots/microbiology ; Plant Stems/microbiology ; Populus/*genetics/microbiology ; Rhizosphere ; Sequence Analysis, DNA/*methods ; Soil Microbiology ; }, abstract = {BACKGROUND: Microorganisms serve important functions within numerous eukaryotic host organisms. An understanding of the variation in the plant niche-level microbiome, from rhizosphere soils to plant canopies, is imperative to gain a better understanding of how both the structural and functional processes of microbiomes impact the health of the overall plant holobiome. Using Populus trees as a model ecosystem, we characterized the archaeal/bacterial and fungal microbiome across 30 different tissue-level niches within replicated Populus deltoides and hybrid Populus trichocarpa × deltoides individuals using 16S and ITS2 rRNA gene analyses.

RESULTS: Our analyses indicate that archaeal/bacterial and fungal microbiomes varied primarily across broader plant habitat classes (leaves, stems, roots, soils) regardless of plant genotype, except for fungal communities within leaf niches, which were greatly impacted by the host genotype. Differences between tree genotypes are evident in the elevated presence of two potential fungal pathogens, Marssonina brunnea and Septoria sp., on hybrid P. trichocarpa × deltoides trees which may in turn be contributing to divergence in overall microbiome composition. Archaeal/bacterial diversity increased from leaves, to stem, to root, and to soil habitats, whereas fungal diversity was the greatest in stems and soils.

CONCLUSIONS: This study provides a holistic understanding of microbiome structure within a bioenergy relevant plant host, one of the most complete niche-level analyses of any plant. As such, it constitutes a detailed atlas or map for further hypothesis testing on the significance of individual microbial taxa within specific niches and habitats of Populus and a baseline for comparisons to other plant species.}, } @article {pmid29433533, year = {2018}, author = {Wærsted, M and Børnick, TS and Twisk, JWR and Veiersted, KB}, title = {Simple descriptive missing data indicators in longitudinal studies with attrition, intermittent missing data and a high number of follow-ups.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {123}, pmid = {29433533}, issn = {1756-0500}, mesh = {*Data Interpretation, Statistical ; *Datasets as Topic ; Humans ; *Longitudinal Studies ; *Research Design ; }, abstract = {OBJECTIVE: Missing data in longitudinal studies may constitute a source of bias. We suggest three simple missing data indicators for the initial phase of getting an overview of the missingness pattern in a dataset with a high number of follow-ups. Possible use of the indicators is exemplified in two datasets allowing wave nonresponse; a Norwegian dataset of 420 subjects examined at 21 occasions during 6.5 years and a Dutch dataset of 350 subjects with ten repeated measurements over a period of 35 years.

RESULTS: The indicators Last response (the timing of last response), Retention (the number of responded follow-ups), and Dispersion (the evenness of the distribution of responses) are introduced. The proposed indicators reveal different aspects of the missing data pattern, and may give the researcher a better insight into the pattern of missingness in a study with several follow-ups, as a starting point for analyzing possible bias. Although the indicators are positively correlated to each other, potential predictors of missingness can have a different relationship with different indicators leading to a better understanding of the missing data mechanism in longitudinal studies. These indictors may be useful descriptive tools when starting to look into a longitudinal dataset with many follow-ups.}, } @article {pmid29433531, year = {2018}, author = {Leyva, FJ and Loughin, CA and Dewey, CW and Marino, DJ and Akerman, M and Lesser, ML}, title = {Histopathologic characteristics of biopsies from dogs undergoing surgery with concurrent gross splenic and hepatic masses: 125 cases (2012-2016).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {122}, pmid = {29433531}, issn = {1756-0500}, mesh = {Animals ; *Dog Diseases/diagnosis/pathology/surgery ; Dogs ; Female ; Hepatectomy/veterinary ; *Liver/pathology/surgery ; *Liver Neoplasms/diagnosis/pathology/surgery ; Male ; *Spleen/pathology/surgery ; Splenectomy/veterinary ; *Splenic Neoplasms/diagnosis/pathology/surgery ; }, abstract = {OBJECTIVE: To investigate the histopathologic characteristics of concurrent splenic and liver masses in dogs undergoing splenectomy and liver mass biopsy/resection. Medical records of 125 client-owned dogs found to have splenic mass or masses and a liver mass or masses during surgery were examined. Signalment (age, sex, breed), body weight, and results of histopathology were recorded for all dogs.

RESULTS: Twenty-seven percent (34/125) of the dogs in this study had no evidence of malignancy in either the liver or the spleen. Sixty of 125 dogs (48.0%) had malignancy in the spleen and liver, and 56 (56/60, 93.3%) of those dogs had the same malignancy in both organs. Signalment was similar to that in other reports of splenic pathology. In this clinical population of dogs, 27% of dogs with concurrent gross splenic and liver masses discovered intraoperatively had benign lesions in both locations and therefore had a favorable prognosis.}, } @article {pmid29433448, year = {2018}, author = {Rakotonirina, H and Kappeler, PM and Fichtel, C}, title = {The role of facial pattern variation for species recognition in red-fronted lemurs (Eulemur rufifrons).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {19}, pmid = {29433448}, issn = {1471-2148}, mesh = {Animals ; Behavior, Animal ; Face ; Facial Recognition/*physiology ; Female ; Geography ; Lemur/*physiology ; Linear Models ; Madagascar ; Male ; Reproduction ; Species Specificity ; Time Factors ; }, abstract = {BACKGROUND: Species recognition, i.e., the ability to distinguish conspecifics from heterospecifics, plays an essential role in reproduction. The role of facial cues for species recognition has been investigated in several non-human primate species except for lemurs. We therefore investigated the role of facial cues for species recognition in wild red-fronted lemurs (Eulemur rufifrons) at Kirindy Forest. We presented adult red-fronted lemurs pictures of male faces from five species including red-fronted lemurs, three closely related species, white-fronted lemurs (E. albifrons), brown lemurs (E. fulvus), rufous brown lemurs (E. rufus), and genetically more distant red-bellied lemurs (E. rubriventer), occurring in allopatry with the study population. We predicted that red-fronted lemurs respond stronger to conspecific than to heterospecific pictures and that females show stronger responses than males. In addition, if genetic drift has played a role in the evolution of facial color patterns in the members of this genus, we predicted that responses of red-fronted lemurs correlate negatively with the genetic distance to the different species stimuli.

RESULTS: Red-fronted lemurs looked significantly longer at pictures of their own species than at those of heterospecifics. Females spent less time looking at pictures of white-fronted, brown and red-bellied lemurs than males did, but not to pictures of red-bellied lemurs and a control stimulus. Individuals also exhibited sniffing behavior while looking at visual stimuli, and the time spent sniffing was significantly longer for pictures of conspecifics compared to those of heterospecifics. Moreover, the time spent looking and sniffing towards the pictures correlated negatively with the genetic distance between their own species and the species presented as stimulus.

CONCLUSIONS: We conclude that red-fronted lemurs have the ability for species recognition using visual facial cues, which may allow them to avoid costly interbreeding. If so, sexual selection might have influenced the evolution of facial patterns in eulemurs. Since responses also correlated with genetic distance, our findings suggest a potential role of genetic drift as well as sexual selection in influencing the evolution of facial variation in eulemurs. Because study subjects looked and sniffed towards the presented pictures, red-fronted lemurs might have the ability for multi-modal species recognition.}, } @article {pmid29433447, year = {2018}, author = {Carraturo, F and De Castro, O and Troisi, J and De Luca, A and Masucci, A and Cennamo, P and Trifuoggi, M and Aliberti, F and Guida, M}, title = {Comparative assessment of the quality of commercial black and green tea using microbiology analyses.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {4}, pmid = {29433447}, issn = {1471-2180}, mesh = {Bacteria/*classification/genetics/*isolation & purification ; Bacterial Load ; Chromatography, High Pressure Liquid ; Colony Count, Microbial ; DNA Barcoding, Taxonomic ; Food Contamination/analysis ; Food Microbiology ; Fungi/*classification/genetics/*isolation & purification ; Italy ; Ochratoxins/analysis ; Plant Leaves/chemistry/*microbiology ; Tea/chemistry/*microbiology ; }, abstract = {BACKGROUND: Drinking tea constitutes a tradition which is deeply rooted in the culture of several countries. Moreover, in recent years, tea consumption is growing all over the world. Improper herbal tea storage (long periods, humid environments) represents a relevant health hazard for consumers because of the growth of bacteria and molds.

RESULTS: This study analyzed 32 samples of commercially available black and green teas - purchased from southern Italy markets and online-shops - and the monitoring of microbiological quality of the tea bag content was performed. Evaluations were conducted with the aim of characterizing pathogens indicated by the European and American guidelines (total bacterial count, fungi and Escherichia coli) and on the research of Pseudomonas spp. and Clostridium perfringens. The presence of ochratoxin A in tea matrix-leaves and infusions was further assessed, using a validated and accredited HPLC-FLD method. Microbial loads, for over 80% samples, ranged from 1.0 × 102 to 2.8 × 105 CFU/g tea: most of identified microorganisms were classified as Bacillaceae. The utilization of rapid detection and identification methods (PCR and sequencing), allowed the characterization of strains of Pseudomonas psychrotolerans, Staphylococcus warneri, Pantoea gaviniae and the isolation of one strain of Clostridium perfringens, whose ability to produce toxins can result in harmful outcomes for consumers. Fungi were isolated from 70% samples: the most prevalent molds were Aspergillus niger strains, followed by Aspergillus tubingensis. Ochratoxin A was detected in 22 of 32 tea solid samples investigated: concentrations resulted over the indicated limits for food products for 50% samples.

CONCLUSIONS: Results obtained demonstrated the need to develop targeted regulations for the safety of herbal teas.}, } @article {pmid29433445, year = {2018}, author = {Lin, H and Yu, M and Wang, X and Zhang, XH}, title = {Comparative genomic analysis reveals the evolution and environmental adaptation strategies of vibrios.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {135}, pmid = {29433445}, issn = {1471-2164}, support = {41730530//National Natural Science Foundation of China/International ; 41476112//National Natural Science Foundation of China/International ; 41521064//National Natural Science Foundation of China/International ; 41506154//National Natural Science Foundation of China/International ; }, mesh = {Adaptation, Physiological/*genetics ; *Evolution, Molecular ; Genetic Variation ; Genome, Bacterial/*genetics ; Genomics/*methods ; High-Throughput Nucleotide Sequencing ; Phylogeny ; Seawater/microbiology ; Species Specificity ; Vibrio/classification/*genetics ; }, abstract = {BACKGROUND: Vibrios are among the most diverse and ecologically important marine bacteria, which have evolved many characteristics and lifestyles to occupy various niches. The relationship between genome features and environmental adaptation strategies is an essential part for understanding the ecological functions of vibrios in the marine system. The advent of complete genome sequencing technology has provided an important method of examining the genetic characteristics of vibrios on the genomic level.

RESULTS: Two Vibrio genomes were sequenced and found to occupy many unique orthologues families which absent from the previously genes pool of the complete genomes of vibrios. Comparative genomics analysis found vibrios encompass a steady core-genome and tremendous pan-genome with substantial gene gain and horizontal gene transfer events in the evolutionary history. Evolutionary analysis based on the core-genome tree suggested that V. fischeri emerged ~ 385 million years ago, along with the occurrence of cephalopods and the flourish of fish. The relatively large genomes, the high number of 16S rRNA gene copies, and the presence of R-M systems and CRISPR system help vibrios live in various marine environments. Chitin-degrading related genes are carried in nearly all the Vibrio genomes. The number of chitinase genes in vibrios has been extremely expanded compared to which in the most recent ancestor of the genus. The chitinase A genes were estimated to have evolved along with the genus, and have undergone significant purifying selective force to conserve the ancestral state.

CONCLUSIONS: Vibrios have experienced extremely genome expansion events during their evolutionary history, allowing them to develop various functions to spread globally. Despite their close phylogenetic relationships, vibrios were found to have a tremendous pan-genome with a steady core-genome, which indicates the highly plastic genome of the genus. Additionally, the existence of various chitin-degrading related genes and the expansion of chitinase A in the genus demonstrate the importance of the chitin utilization for vibrios. Defensive systems in the Vibrio genomes may protect them from the invasion of external DNA. These genomic features investigated here provide a better knowledge of how the evolutionary process has forged Vibrio genomes to occupy various niches.}, } @article {pmid29433444, year = {2018}, author = {Hücker, SM and Vanderhaeghen, S and Abellan-Schneyder, I and Wecko, R and Simon, S and Scherer, S and Neuhaus, K}, title = {A novel short L-arginine responsive protein-coding gene (laoB) antiparallel overlapping to a CadC-like transcriptional regulator in Escherichia coli O157:H7 Sakai originated by overprinting.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {21}, pmid = {29433444}, issn = {1471-2148}, support = {SCHE316/3-1,2,3//Deutsche Forschungsgemeinschaft/International ; KE740/13-1,2,3//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Arginine/*metabolism ; Base Sequence ; Escherichia coli O157/*genetics/growth & development/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Genes, Bacterial ; *Genes, Overlapping ; Green Fluorescent Proteins/metabolism ; Mutation/genetics ; Open Reading Frames/*genetics ; Phylogeny ; Promoter Regions, Genetic ; Protein Biosynthesis ; Recombinant Fusion Proteins/metabolism ; Trans-Activators/*metabolism ; *Transcription, Genetic ; Transcriptome/genetics ; }, abstract = {BACKGROUND: Due to the DNA triplet code, it is possible that the sequences of two or more protein-coding genes overlap to a large degree. However, such non-trivial overlaps are usually excluded by genome annotation pipelines and, thus, only a few overlapping gene pairs have been described in bacteria. In contrast, transcriptome and translatome sequencing reveals many signals originated from the antisense strand of annotated genes, of which we analyzed an example gene pair in more detail.

RESULTS: A small open reading frame of Escherichia coli O157:H7 strain Sakai (EHEC), designated laoB (L-arginine responsive overlapping gene), is embedded in reading frame -2 in the antisense strand of ECs5115, encoding a CadC-like transcriptional regulator. This overlapping gene shows evidence of transcription and translation in Luria-Bertani (LB) and brain-heart infusion (BHI) medium based on RNA sequencing (RNAseq) and ribosomal-footprint sequencing (RIBOseq). The transcriptional start site is 289 base pairs (bp) upstream of the start codon and transcription termination is 155 bp downstream of the stop codon. Overexpression of LaoB fused to an enhanced green fluorescent protein (EGFP) reporter was possible. The sequence upstream of the transcriptional start site displayed strong promoter activity under different conditions, whereas promoter activity was significantly decreased in the presence of L-arginine. A strand-specific translationally arrested mutant of laoB provided a significant growth advantage in competitive growth experiments in the presence of L-arginine compared to the wild type, which returned to wild type level after complementation of laoB in trans. A phylostratigraphic analysis indicated that the novel gene is restricted to the Escherichia/Shigella clade and might have originated recently by overprinting leading to the expression of part of the antisense strand of ECs5115.

CONCLUSIONS: Here, we present evidence of a novel small protein-coding gene laoB encoded in the antisense frame -2 of the annotated gene ECs5115. Clearly, laoB is evolutionarily young and it originated in the Escherichia/Shigella clade by overprinting, a process which may cause the de novo evolution of bacterial genes like laoB.}, } @article {pmid29433443, year = {2018}, author = {Nyirenda, SS and Hang Ombe, BM and Simulundu, E and Mulenga, E and Moonga, L and Machang U, RS and Misinzo, G and Kilonzo, BS}, title = {Molecular epidemiological investigations of plague in Eastern Province of Zambia.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {2}, pmid = {29433443}, issn = {1471-2180}, support = {2012-3166/001//Intra-ACP Academic mobility scheme Africa (Mwalimu Nyerere) and the "Caribbean and Pacific under the commission of the European Union"/International ; }, mesh = {Animals ; Bacterial Proteins/*genetics ; Congo ; DNA, Bacterial/genetics ; Disease Outbreaks ; Disease Reservoirs/*microbiology ; Epidemiological Monitoring/veterinary ; Evolution, Molecular ; Goats ; Humans ; Kenya ; *Molecular Epidemiology ; Phylogeny ; Plague/epidemiology/*microbiology/transmission ; Plasminogen Activators/*genetics ; Polymerase Chain Reaction/veterinary ; Rodentia/microbiology/parasitology ; Sequence Analysis ; Shrews ; Siphonaptera/microbiology ; Swine ; Yersinia pestis/classification/*genetics/*isolation & purification ; Zambia ; }, abstract = {BACKGROUND: Plague is a flea-borne zoonotic and invasive disease caused by a gram negative coccobacillus bacterium called Yersinia pestis. Plague has caused three devastating pandemics globally namely: the Justinian, Black Death and Oriental plague. The disease in the Eastern Province of Zambia has been reported in Nyimba and Sinda Districts in the past 15 years. The aim of this study was to investigate the molecular epidemiology of plague in the two affected districts. Polymerase Chain Reaction (PCR), targeting Plasminogen activator gene (pla gene) of Y. pestis, was performed on suspected human bubo aspirates (n = 7), rodents (n = 216), shrews (n = 27) and fleas (n = 1494). Of these, one positive sample from each source or host was subjected to sequencing followed by phylogenetic analysis.

RESULTS: The plasminogen activator gene (pla gene) of Y. pestis was detected in 42.8% bubo aspirates, 6.9% rodents, 3.7% shrew and 0.8% fleas. The fleas were from pigs (n = 4), goats (n = 5) and rodents (n = 3). The sequencing and phylogenetic analysis suggested that the pla gene of Y. pestis in Nyimba and Sinda was similar and the isolates demonstrated a high degree of evolutionary relationship with Antiqua strains from the Republic of Congo and Kenya.

CONCLUSION: It can be concluded that pla gene of Y. pestis was present in various hosts in the two districts and the strains circulating in each district were similar and resembles those in the Republic of Congo and Kenya.}, } @article {pmid29433440, year = {2018}, author = {Shankar, C and Veeraraghavan, B and Nabarro, LEB and Ravi, R and Ragupathi, NKD and Rupali, P}, title = {Whole genome analysis of hypervirulent Klebsiella pneumoniae isolates from community and hospital acquired bloodstream infection.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {6}, pmid = {29433440}, issn = {1471-2180}, mesh = {Adult ; Aged ; Aged, 80 and over ; Bacteremia/*microbiology ; Bacterial Capsules/genetics ; Bacterial Proteins/genetics ; Community-Acquired Infections/microbiology ; Cross Infection/*genetics ; Female ; Genes, Bacterial/genetics ; Genome, Bacterial/genetics ; Genotype ; Humans ; India ; Klebsiella Infections/epidemiology/*microbiology ; Klebsiella pneumoniae/*genetics/*isolation & purification/pathogenicity ; Liver Diseases/microbiology ; Male ; Microbial Sensitivity Tests ; Middle Aged ; *Molecular Epidemiology ; Phylogeny ; Siderophores/genetics ; Transcription Factors/genetics ; Treatment Outcome ; Virulence/genetics ; Virulence Factors/*genetics ; *Whole Genome Sequencing ; }, abstract = {BACKGROUND: Hypervirulent K. pneumoniae (hvKp) causes severe community acquired infections, predominantly in Asia. Though initially isolated from liver abscesses, they are now prevalent among invasive infections such as bacteraemia. There have been no studies reported till date on the prevalence and characterisation of hvKp in India. The objective of this study is to characterise the hypervirulent strains isolated from bacteraemic patients for determination of various virulence genes and resistance genes and also to investigate the difference between healthcare associated and community acquired hvKp with respect to clinical profile, antibiogram, clinical outcome and molecular epidemiology.

RESULTS: Seven isolates that were susceptible to all of the first and second line antimicrobials and phenotypically identified by positive string test were included in the study. They were then confirmed genotypically by presence of rmpA and rmpA2 by PCR. Among the study isolates, four were from patients with healthcare associated infections; none were fatal. All patients with community acquired infection possessed chronic liver disease with fatal outcome. Genes encoding for siderophores such as aerobactin, enterobactin, yersiniabactin, allantoin metabolism and iron uptake were identified by whole genome sequencing. Five isolates belonged to K1 capsular type including one K. quasipneumoniae. None belonged to K2 capsular type. Four isolates belonged to the international clone ST23 among which three were health-care associated and possessed increased virulence genes. Two novel sequence types were identified in the study; K. pneumoniae belonging to ST2319 and K. quasipneumoniae belonging to ST2320. Seventh isolate belonged to ST420.

CONCLUSION: This is the first report on whole genome analysis of hypervirulent K. pneumoniae from India. The novel sequence types described in this study indicate that these strains are evolving and hvKp is now spread across various clonal types. Studies to monitor the prevalence of hvKp is needed since there is a potential for the community acquired isolates to develop multidrug resistance in hospital environment and may pose a major challenge for clinical management.}, } @article {pmid29433439, year = {2018}, author = {Yu, X and Noll, RR and Romero Dueñas, BP and Allgood, SC and Barker, K and Caplan, JL and Machner, MP and LaBaer, J and Qiu, J and Neunuebel, MR}, title = {Legionella effector AnkX interacts with host nuclear protein PLEKHN1.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {5}, pmid = {29433439}, issn = {1471-2180}, support = {P20 GM103446/GM/NIGMS NIH HHS/United States ; 15A00752//University of Delaware Research Foundation/International ; 81673040//National Natural Science Foundation of China/International ; SKLP-O201504//State Key Laboratory of Proteomics/International ; IIA-1301765//National Science Foundation/International ; }, mesh = {Ankyrin Repeat/genetics/*physiology ; Bacterial Proteins/*metabolism ; Cell Membrane/metabolism ; Endocytosis/physiology ; HEK293 Cells ; HeLa Cells ; Host-Pathogen Interactions/*physiology ; Humans ; Legionella pneumophila/*metabolism/pathogenicity ; Legionnaires' Disease/*metabolism ; Lipid-Linked Proteins/*metabolism ; Lysosomes/metabolism ; Macrophages/microbiology ; Nuclear Proteins ; Recombinant Proteins ; Vacuoles/metabolism ; rab GTP-Binding Proteins/metabolism ; }, abstract = {BACKGROUND: The intracellular bacterial pathogen Legionella pneumophila proliferates in human alveolar macrophages, resulting in a severe pneumonia termed Legionnaires' disease. Throughout the course of infection, L. pneumophila remains enclosed in a specialized membrane compartment that evades fusion with lysosomes. The pathogen delivers over 300 effector proteins into the host cell, altering host pathways in a manner that sets the stage for efficient pathogen replication. The L. pneumophila effector protein AnkX targets host Rab GTPases and functions in preventing fusion of the Legionella-containing vacuole with lysosomes. However, the current understanding of AnkX's interaction with host proteins and the means through which it exerts its cellular function is limited.

RESULTS: Here, we investigated the protein interaction network of AnkX by using the nucleic acid programmable protein array (NAPPA), a high-density platform comprising 10,000 unique human ORFs. This approach facilitated the discovery of PLEKHN1 as a novel interaction partner of AnkX. We confirmed this interaction through multiple independent in vitro pull-down, co-immunoprecipitation, and cell-based assays. Structured illumination microscopy revealed that endogenous PLEKHN1 is found in the nucleus and on vesicular compartments, whereas ectopically produced AnkX co-localized with lipid rafts at the plasma membrane. In mammalian cells, HaloTag-AnkX co-localized with endogenous PLEKHN1 on vesicular compartments. A central fragment of AnkX (amino acids 491-809), containing eight ankyrin repeats, extensively co-localized with endogenous PLEKHN1, indicating that this region may harbor a new function. Further, we found that PLEKHN1 associated with multiple proteins involved in the inflammatory response.

CONCLUSIONS: Altogether, our study provides evidence that in addition to Rab GTPases, the L. pneumophila effector AnkX targets nuclear host proteins and suggests that AnkX may have novel functions related to manipulating the inflammatory response.}, } @article {pmid29433437, year = {2018}, author = {Lee, JH and Heo, S and Jeong, DW}, title = {Genomic insights into Staphylococcus equorum KS1039 as a potential starter culture for the fermentation of high-salt foods.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {136}, pmid = {29433437}, issn = {1471-2164}, support = {NRF-2016R1D1A1B01011421//National Research Foundation of Korea/International ; NRF 2016R1D1A1B03930239//National Research Foundation of Korea/International ; }, mesh = {Bacteriocins/genetics/metabolism ; Energy Metabolism/genetics ; *Fermentation ; Flavoring Agents/metabolism ; Food Microbiology/*methods ; Genes, Bacterial/genetics ; Genome, Bacterial/*genetics ; Genomics/*methods ; Metabolic Networks and Pathways/genetics ; Species Specificity ; Staphylococcus/classification/*genetics/metabolism ; }, abstract = {BACKGROUND: Our previous comparative genomic analysis of Staphylococcus equorum KS1039 with five S. equorum strains illuminated the genomic basis of its safety and salt tolerance. However, a comprehensive picture of the cellular components and metabolic pathways involved in the degradation of macromolecules and development of sensory properties has not been obtained for S. equorum. Therefore, in this study, we examined the general metabolism of S. equorum based on information obtained from published complete genome sequences of six S. equorum strains isolated from different niches. Additionally, the utility of strain KS1039 as a starter culture for high-salt food fermentations was examined.

RESULTS: All six S. equorum strains contained genes involved in glycolysis, the tricarboxylic acid cycle, and amino acid metabolic pathways, as well as color development. Moreover, the strains had the potential to produce acetoin, butanediol, and branched chain fatty acids, all of which are important flavor compounds. None of the strains contained decarboxylase genes, which are required for histamine and tyramine production. Strain KS1039 contained bacteriocin and CRISPR/Cas gene clusters, and experimental results suggested that these genes were functional in vitro.

CONCLUSIONS: The comparative genomic analysis carried out herein provides important information on the usefulness of S. equorum KS1039 as a starter culture for the fermentation of high-salt foods in terms of safety, salt tolerance, bacteriocin production, and foreign plasmid restriction.}, } @article {pmid29433435, year = {2018}, author = {Thangavel, K and Radha Krishnan, P and Nagaiah, S and Kuppusamy, S and Chinnasamy, S and Rajadorai, JS and Nellaiappan Olaganathan, G and Dananjeyan, B}, title = {Growth and metabolic characteristics of oleaginous microalgal isolates from Nilgiri biosphere Reserve of India.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {1}, pmid = {29433435}, issn = {1471-2180}, support = {F. No. 41-1240/2012 (SR) dated 23.07.2012//University Grants Commission/International ; }, mesh = {Biodiversity ; *Biofuels ; Biomass ; Carbohydrates/analysis ; Chlorella ; Culture Media ; Esters/analysis ; Fatty Acids/analysis ; Forests ; Hydrogen-Ion Concentration ; India ; Lipids/analysis ; Microalgae/classification/*growth & development/*isolation & purification/*metabolism ; Phylogeny ; Proteins/analysis ; RNA, Ribosomal, 18S/genetics ; Soil Microbiology ; Temperature ; Volvocida ; Water Microbiology ; }, abstract = {BACKGROUND: Renewable energy for sustainable development is a subject of a worldwide debate since continuous utilization of non-renewable energy sources has a drastic impact on the environment and economy; a search for alternative energy resources is indispensable. Microalgae are promising and potential alternate energy resources for biodiesel production. Thus, our efforts were focused on surveying the natural diversity of microalgae for the production of biodiesel. The present study aimed at identification, isolation, and characterization of oleaginous microalgae from shola forests of Nilgiri Biosphere Reserve (NBR), the biodiversity hot spot of India, where the microalgal diversity has not yet been systematically investigated.

RESULTS: Overall the higher biomass yield, higher lipid accumulation and thermotolerance observed in the isolated microalgal strains have been found to be the desirable traits for the efficient biodiesel production. Species composition and diversity analysis yielded ten potential microalgal isolates belonging to Chlorophyceae and Cyanophyceae classes. The chlorophytes exhibited higher growth rate, maximum biomass yield, and higher lipid accumulation than Cyanophyceae. Among the chlorophytes, the best performing strains were identified and represented by Acutodesmus dissociatus (TGA1), Chlorella sp. (TGA2), Chlamydomonadales sp. (TGA3) and Hindakia tetrachotoma (PGA1). The Chlamydomonadales sp. recorded with the highest growth rate, lipid accumulation and biomass yield of 0.28 ± 0.03 day-1 (μexp), 29.7 ± 0.69% and 134.17 ± 16.87 mg L-1 day-1, respectively. It was also found to grow well at various temperatures, viz., 25 °C, 35 °C, and 45 °C, indicating its suitability for open pond cultivation. The fatty acid methyl ester (FAME) analysis of stationary phase cultures of selected four algal strains by tandem mass spectrograph showed C16:0, C18:1 and C18:3 as dominant fatty acids suitable for biodiesel production. All the three strains except for Hindakia tetrachotoma (PGA1) recorded higher carbohydrate content and were considered as potential feed stocks for biodiesel production through hydrothermal liquefaction technology (HTL).

CONCLUSIONS: In conclusion, the present investigation is a first systematic study on the microalgal diversity of soil and water samples from selected sites of NBR. The study resulted in isolation and characterization of ten potent oleaginous microalgae and found four cultures as promising feed stocks for biodiesel production. Of the four microalgae, Chlamydomonadales sp. (TGA3) was found to be significantly thermo-tolerant and can be considered as promising feedstock for biodiesel production.}, } @article {pmid29433434, year = {2018}, author = {Yi, L and Chen, C and Yin, S and Li, H and Li, Z and Wang, B and King, GJ and Wang, J and Liu, K}, title = {Sequence variation and functional analysis of a FRIGIDA orthologue (BnaA3.FRI) in Brassica napus.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {32}, pmid = {29433434}, issn = {1471-2229}, support = {31471531//National Natural Science Foundation of China/International ; 2015CB150200//National Basic Research and Development Programme of China/International ; }, mesh = {Base Sequence ; Brassica napus/*genetics/metabolism ; Genetic Variation ; Haplotypes/genetics ; Plant Proteins/*genetics/metabolism ; }, abstract = {BACKGROUND: Allelic variation at the FRIGIDA (FRI) locus is a major contributor to natural variation of flowering time and vernalization requirement in Arabidopsis thaliana. Dominant FRI inhibits flowering by activating the expression of the MADS box transcriptional repressor FLOWERING LOCUS C (FLC), which represses flowering prior to vernalization. Four FRI orthologues had been identified in the domesticated amphidiploid Brassica napus. Linkage and association studies had revealed that one of the FRI orthologues, BnaA3.FRI, contributes to flowering time variation and crop type differentiation.

RESULTS: Sequence analyses indicated that three out of the four BnaFRI paralogues, BnaA3.FRI, BnaA10.FRI and BnaC3.FRI, contained a large number of polymorphic sites. Haplotype analysis in a panel of 174 B. napus accessions using PCR markers showed that all the three paralogues had a biased distribution of haplotypes in winter type oilseed rape (P < 0.01). Association analysis indicated that only BnaA3.FRI contributes to flowering time variation in B. napus. In addition, transgenic functional complementation demonstrated that mutations in the coding sequence of BnaA3.FRI lead to weak alleles, and subsequently to flowering time variation.

CONCLUSION: This study for the first time provides a molecular basis for flowering time control by BnaA3.FRI in B. napus, and will facilitate predictive oilseed rape breeding to select varieties with favorable flowering time and better adaption to latitude and seasonal shifts due to changing climate.}, } @article {pmid29433432, year = {2018}, author = {Wang, F and Dohogne, Z and Yang, J and Liu, Y and Soibam, B}, title = {Predictors of breast cancer cell types and their prognostic power in breast cancer patients.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {137}, pmid = {29433432}, issn = {1471-2164}, support = {68847-MA-REP/W911NF-16-1-0480//U.S. Department of Defense/International ; }, mesh = {Biomarkers, Tumor/*genetics ; Breast Neoplasms/*genetics/pathology ; Cluster Analysis ; Female ; Gene Expression Profiling/*methods/statistics & numerical data ; *Gene Expression Regulation, Neoplastic ; Humans ; Prognosis ; Proportional Hazards Models ; Sequence Analysis, RNA/methods ; Single-Cell Analysis/methods ; Survival Analysis ; }, abstract = {BACKGROUND: Comprehensive understanding of intratumor heterogeneity requires identification of molecular markers, which are capable of differentiating different subpopulations and which also have clinical significance. One important tool that has been addressing this issue is single cell RNA-Sequencing (scRNASeq) that allows the quantification of expression profiles of transcripts in individual cells in a population of cancer cells. Using the expression profiles from scRNASeq, current studies conduct analysis to group cells into different subpopulations using clustering algorithms. In this study, we explore scRNASeq cancer data from a different perspective. We focus on scRNASeq data originating from cancer cells pertaining to a particular cancer type, where the cell type or the subpopulation to which each cell belongs is known. We investigate if the "cell type" of a cancer cell can be predicted based on the expression profiles of a small set of transcripts.

RESULTS: We outline a predictive analytics pipeline to accurately predict 6 breast cancer cell types using single cell gene expression profiles. Instead of building predictive models using the complete human transcripts, the pipeline first eliminates predictors with low expression and low variance. A multinomial penalized logistic regression further reduces the size of the predictors to only 308, out of which 34 are long non-coding RNAs. Tuning of predictive models shows support vector machines and neural networks as the most accurate models achieving close to 98% prediction accuracies. We also find that mixture of protein coding genes and long non-coding RNAs are better predictors compared to when the two sets of transcripts are treated separately. A signature risk score originating from 65 protein coding genes and 5 lncRNA predictors is associated with prognostic survival of TCGA breast cancer patients. This association was maintained when the risk scores were generated using 65 PCGs and 5 lncRNA separately. We further show that predictors restricted to a particular cell type serve as better prognostic markers for the respective patient subtype.

CONCLUSION: Our results show that in general, the breast cancer cell type predictors are also associated with patient survivability and hence have clinical significance.}, } @article {pmid29433427, year = {2018}, author = {Deng, G and Yang, J and Zhang, Q and Xiao, ZX and Cai, H}, title = {MethCNA: a database for integrating genomic and epigenomic data in human cancer.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {138}, pmid = {29433427}, issn = {1471-2164}, support = {31571314//National Natural Science Foundation of China/International ; U1603120//National Natural Science Foundation of China/International ; }, mesh = {Computational Biology/*methods ; DNA Copy Number Variations ; DNA Methylation ; DNA, Neoplasm/genetics ; *Databases, Genetic ; Epigenomics/*methods ; Gene Expression Profiling/methods ; Genomics/*methods ; Humans ; Internet ; Neoplasms/classification/*genetics ; Reproducibility of Results ; }, abstract = {BACKGROUND: The integration of DNA methylation and copy number alteration data promises to provide valuable insight into the underlying molecular mechanisms responsible for cancer initiation and progression. However, the generation and processing of these datasets are costly and time-consuming if carried out separately. The Illumina Infinium HumanMethylation450 BeadChip, initially designed for the evaluation of DNA methylation levels, allows copy number variant calling using bioinformatics tools.

RESULTS: A substantial amount of Infinium HumanMethylation450 data across various cancer types has been accumulated in recent years and is a valuable resource for large-scale data analysis. Here we present MethCNA, a comprehensive database for genomic and epigenomic data integration in human cancer. In the current release, MethCNA contains about 10,000 tumor samples representing 37 cancer types. All raw array data were collected from The Cancer Genome Atlas and NCBI Gene Expression Omnibus database and analyzed using a pipeline that integrated multiple computational resources and tools. The normalized copy number aberration data and DNA methylation alterations were obtained. We provide a user-friendly web-interface for data mining and visualization.

CONCLUSIONS: The Illumina Infinium HumanMethylation450 BeadChip enables the interrogation and integration of both genomic and epigenomic data from exactly the same DNA specimen, and thus can aid in distinguishing driver from passenger mutations in cancer. We expect MethCNA will enable researchers to explore DNA methylation and copy number alteration patterns, identify key oncogenic drivers in cancer, and assist in the development of targeted therapies. MethCNA is publicly available online at http://cgma.scu.edu.cn/MethCNA .}, } @article {pmid29433425, year = {2018}, author = {Anderson, CS and McCall, PR and Stern, HA and Yang, H and Topham, DJ}, title = {Antigenic cartography of H1N1 influenza viruses using sequence-based antigenic distance calculation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {51}, pmid = {29433425}, issn = {1471-2105}, support = {HHSN272201400005C//National Institute of Allergy and Infectious Diseases/International ; }, mesh = {Algorithms ; Amino Acid Sequence ; Antigens, Viral/*chemistry/*immunology ; Epitope Mapping ; Epitopes/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry/genetics ; Humans ; Influenza A Virus, H1N1 Subtype/*immunology ; Reproducibility of Results ; }, abstract = {BACKGROUND: The ease at which influenza virus sequence data can be used to estimate antigenic relationships between strains and the existence of databases containing sequence data for hundreds of thousands influenza strains make sequence-based antigenic distance estimates an attractive approach to researchers. Antigenic mismatch between circulating strains and vaccine strains results in significantly decreased vaccine effectiveness. Furthermore, antigenic relatedness between the vaccine strain and the strains an individual was originally primed with can affect the cross-reactivity of the antibody response. Thus, understanding the antigenic relationships between influenza viruses that have circulated is important to both vaccinologists and immunologists.

RESULTS: Here we develop a method of mapping antigenic relationships between influenza virus stains using a sequence-based antigenic distance approach (SBM). We used a modified version of the p-all-epitope sequence-based antigenic distance calculation, which determines the antigenic relatedness between strains using influenza hemagglutinin (HA) genetic coding sequence data and provide experimental validation of the p-all-epitope calculation. We calculated the antigenic distance between 4838 H1N1 viruses isolated from infected humans between 1918 and 2016. We demonstrate, for the first time, that sequence-based antigenic distances of H1N1 Influenza viruses can be accurately represented in 2-dimenstional antigenic cartography using classic multidimensional scaling. Additionally, the model correctly predicted decreases in cross-reactive antibody levels with 87% accuracy and was highly reproducible with even when small numbers of sequences were used.

CONCLUSION: This work provides a highly accurate and precise bioinformatics tool that can be used to assess immune risk as well as design optimized vaccination strategies. SBM accurately estimated the antigenic relationship between strains using HA sequence data. Antigenic maps of H1N1 virus strains reveal that strains cluster antigenically similar to what has been reported for H3N2 viruses. Furthermore, we demonstrated that genetic variation differs across antigenic sites and discuss the implications.}, } @article {pmid29433424, year = {2018}, author = {Pandey, B and Grover, A and Sharma, P}, title = {Molecular dynamics simulations revealed structural differences among WRKY domain-DNA interaction in barley (Hordeum vulgare).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {132}, pmid = {29433424}, issn = {1471-2164}, mesh = {Amino Acid Sequence ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Gene Expression Regulation, Plant ; Genetic Variation ; Hordeum/genetics/*metabolism ; *Molecular Dynamics Simulation ; Phylogeny ; Plant Proteins/classification/genetics/*metabolism ; Protein Binding ; Protein Conformation ; Sequence Homology, Amino Acid ; Transcription Factors/chemistry/genetics/*metabolism ; }, abstract = {BACKGROUND: The WRKY transcription factors are a class of DNA-binding proteins involved in diverse plant processes play critical roles in response to abiotic and biotic stresses. Genome-wide divergence analysis of WRKY gene family in Hordeum vulgare provided a framework for molecular evolution and functional roles. So far, the crystal structure of WRKY from barley has not been resolved; moreover, knowledge of the three-dimensional structure of WRKY domain is pre-requisites for exploring the protein-DNA recognition mechanisms. Homology modelling based approach was used to generate structures for WRKY DNA binding domain (DBD) and its variants using AtWRKY1 as a template. Finally, the stability and conformational changes of the generated model in unbound and bound form was examined through atomistic molecular dynamics (MD) simulations for 100 ns time period.

RESULTS: In this study, we investigated the comparative binding pattern of WRKY domain and its variants with W-box cis-regulatory element using molecular docking and dynamics (MD) simulations assays. The atomic insight into WRKY domain exhibited significant variation in the intermolecular hydrogen bonding pattern, leading to the structural anomalies in the variant type and differences in the DNA-binding specificities. Based on the MD analysis, residual contribution and interaction contour, wild-type WRKY (HvWRKY46) were found to interact with DNA through highly conserved heptapeptide in the pre- and post-MD simulated complexes, whereas heptapeptide interaction with DNA was missing in variants (I and II) in post-MD complexes. Consequently, through principal component analysis, wild-type WRKY was also found to be more stable by obscuring a reduced conformational space than the variant I (HvWRKY34). Lastly, high binding free energy for wild-type and variant II allowed us to conclude that wild-type WRKY-DNA complex was more stable relative to variants I.

CONCLUSIONS: The results of our study revealed complete dynamic and structural information about WRKY domain-DNA interactions. However, no structure base information reported to date for WRKY variants and their mechanism of interaction with DNA. Our findings highlighted the importance of selecting a sequence to generate newer transgenic plants that would be increasingly tolerance to stress conditions.}, } @article {pmid29433423, year = {2018}, author = {Huang, N and Li, W and Wang, X and Qi, S}, title = {MicroRNA-17-5p aggravates lipopolysaccharide-induced injury in nasal epithelial cells by targeting Smad7.}, journal = {BMC cell biology}, volume = {19}, number = {1}, pages = {1}, pmid = {29433423}, issn = {1471-2121}, mesh = {Cell Line ; Cytokines/metabolism ; Epithelial Cells/*pathology ; Humans ; Inflammation Mediators/metabolism ; Lipopolysaccharides ; MicroRNAs/genetics/*metabolism ; NF-kappa B/metabolism ; Nasal Cavity/*pathology ; Smad7 Protein/*genetics/metabolism ; Transfection ; Wnt Signaling Pathway ; }, abstract = {BACKGROUND: Globally, rhinitis is one of the most common chronic disorders. Despite availability of drugs to manage the symptomatology of rhinitis, researchers still focus on identification of novel molecular targets for better management. MicroRNAs are implicated in many biological and pathological processes. However, the role of miR-17-5p in rhinitis remains unexplored. This study aimed to explore the role of miR-17-5p in lipopolysaccharide (LPS)-induced injury of nasal epithelial RPMI2650 cells and to elucidate the possible underlying molecular mechanism.

RESULTS: LPS damaged RPMI2650 cells by inhibiting cell proliferation, promoting apoptosis, and stimulating the release of inflammatory cytokines. miR-17-5p expression was significantly increased in RPMI2650 cells following treatment with LPS. Furthermore, it was found that overexpression of miR-17-5p led to aggravation of LPS-induced injury. miR-17-5p negatively regulated expression of Smad7; overexpression of Smad7 protected the RPMI2650 cells by inactivating NF-κB and Wnt/β catenin pathways and vice versa.

CONCLUSIONS: Overexpression of miR-17-5p aggravated LPS-induced damage of RPMI2650 cells. Expression of Smad7 was negatively regulated by miR-17-5p; Smad7 expression inactivated NF-κB and Wnt/β catenin pathways.}, } @article {pmid29433421, year = {2018}, author = {Li, Q and Dong, K and Xu, L and Jia, X and Wu, J and Sun, W and Zhang, X and Fu, S}, title = {The distribution of three candidate cold-resistant SNPs in six minorities in North China.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {134}, pmid = {29433421}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Adaptation, Physiological/*genetics ; Asian Continental Ancestry Group/genetics ; Carnitine O-Palmitoyltransferase/genetics ; China ; *Cold Temperature ; Ethnic Groups/classification/*genetics ; Fatty Acid Desaturases/genetics ; Gene Frequency ; Genotype ; Humans ; Linkage Disequilibrium ; Phylogeny ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Heilongjiang Province located in northeast China is a multi-ethnic region with people who have lived in cold conditions for several generations. Fatty acids are important to people with cold resistance. CPT1A encodes a protein that imports long-chain fatty acids into the mitochondria for fatty-acid oxidation. FADS is an essential enzyme for the synthesis of long-chain polyunsaturated fatty acids.

RESULTS: In the present study, we investigated the distributions of three cold resistance-related SNPs (rs80356779 G > A in CPT1A, rs7115739 T > G in FADS3 and rs174570 C > T in FADS2) from six populations that included 1093 individuals who have lived in Heilongjiang Province for at least three generations. The frequencies of rs174570 and rs7115739 were different in our six north minorities compared to the Chinese Dai in Xishuangbanna (CDX) in southern China. All the SNPs in Hezhen were significantly different from other five studied populations. In addition, the genetic distribution of rs174570 in Daur was significantly different from Manchu and Korea, and the frequency of rs7115739 in Ewenki was significantly different from the other populations. The results also showed that the frequencies of the three SNPs in the six minorities were different from those of Greenlandic Inuit and Siberian population.

CONCLUSIONS: Our results showed the distributions of the three cold resistance-related SNPs from six populations that included 1093 individuals in northern China. Distributions of the allele frequencies for the cold resistance-related SNPs in northern China were statistically different from those in southern China. These data help to establish the DNA genome database for the six populations and fully preserve existing minority genetic information.}, } @article {pmid29433420, year = {2018}, author = {Nuez-Ortín, WG and Carter, CG and Nichols, PD and Cooke, IR and Wilson, R}, title = {Liver proteome response of pre-harvest Atlantic salmon following exposure to elevated temperature.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {133}, pmid = {29433420}, issn = {1471-2164}, mesh = {Adaptation, Physiological ; Animals ; Fish Proteins/*metabolism ; Liver/*metabolism ; Protein Interaction Maps ; Proteome/*metabolism ; Proteomics/*methods ; Salmo salar/*metabolism ; Seasons ; Tasmania ; *Temperature ; }, abstract = {BACKGROUND: Atlantic salmon production in Tasmania (Southern Australia) occurs near the upper limits of the species thermal tolerance. Summer water temperatures can average over 19 °C over several weeks and have negative effects on performance and health. Liver tissue exerts important metabolic functions in thermal adaptation. With the aim of identifying mechanisms underlying liver plasticity in response to chronic elevated temperature in Atlantic salmon, label-free shotgun proteomics was used to explore quantitative protein changes after 43 days of exposure to elevated temperature.

RESULTS: A total of 276 proteins were differentially (adjusted p-value < 0.05) expressed between the control (15 °C) and elevated (21 °C) temperature treatments. As identified by Ingenuity Pathway Analysis (IPA), transcription and translation mechanisms, protein degradation via the proteasome, and cytoskeletal components were down-regulated at elevated temperature. In contrast, an up-regulated response was identified for NRF2-mediated oxidative stress, endoplasmic reticulum stress, and amino acid degradation. The proteome response was paralleled by reduced fish condition factor and hepato-somatic index at elevated temperature.

CONCLUSIONS: The present study provides new evidence of the interplay among different cellular machineries in a scenario of heat-induced energy deficit and oxidative stress, and refines present understanding of how Atlantic salmon cope with chronic exposure to temperature near the upper limits of thermal tolerance.}, } @article {pmid29433348, year = {2018}, author = {Redlick, MH and Vangelisti, AL}, title = {Affection, Deception, and Evolution: Deceptive Affectionate Messages as Mate Retention Behaviors.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704917753857}, doi = {10.1177/1474704917753857}, pmid = {29433348}, issn = {1474-7049}, mesh = {Adult ; Aged ; Biological Evolution ; Communication ; *Deception ; Female ; Humans ; *Interpersonal Relations ; Male ; Middle Aged ; *Personal Satisfaction ; Sexual Behavior/*psychology ; Sexual Partners/*psychology ; Young Adult ; }, abstract = {This study explored how partner mate value (PMV) and factors indicative of the relational climate (i.e., commitment and satisfaction) might affect individuals' tendency to use deceptive affectionate messages (DAMs). Participants (N = 203) responded to a survey including measures regarding these variables. Contrary to predictions, PMV and the tendency to engage in DAMs were significantly and negatively associated with one another. Analyses further indicated that commitment significantly moderated the negative association between PMV and DAMs. The present study also provided evidence that when commitment to the relationship is low, satisfaction mediates the negative association between PMV and DAMs.}, } @article {pmid29433126, year = {2018}, author = {Lavoie, H and Sahmi, M and Maisonneuve, P and Marullo, SA and Thevakumaran, N and Jin, T and Kurinov, I and Sicheri, F and Therrien, M}, title = {MEK drives BRAF activation through allosteric control of KSR proteins.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {549-553}, pmid = {29433126}, issn = {1476-4687}, support = {P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; }, mesh = {Allosteric Regulation ; Crystallography, X-Ray ; Enzyme Activation ; Humans ; MAP Kinase Kinase 1/metabolism ; MAP Kinase Kinase 2/metabolism ; Mitogen-Activated Protein Kinase Kinases/*metabolism ; Models, Molecular ; Phosphorylation ; Protein Binding ; Protein Domains ; Protein Kinases/*chemistry/*metabolism ; Protein Multimerization ; Protein-Serine-Threonine Kinases/metabolism ; Proto-Oncogene Proteins B-raf/*chemistry/*metabolism ; Signal Transduction ; }, abstract = {RAF family kinases have prominent roles in cancer. Their activation is dependent on dimerization of their kinase domains, which has emerged as a hindrance for drug development. In mammals, RAF family kinases include three catalytically competent enzymes (ARAF, BRAF and CRAF) and two pseudokinases (KSR1 and KSR2) that have been described as scaffolds owing to their apparent ability to bridge RAF isoforms and their substrate, mitogen-activated protein kinase kinase (MEK). Kinase suppressor of Ras (KSR) pseudokinases were also shown to dimerize with kinase-competent RAFs to stimulate catalysis allosterically. Although GTP-bound RAS can modulate the dimerization of RAF isoforms by engaging their RAS-binding domains, KSR1 and KSR2 lack an RAS-binding domain and therefore the regulatory principles underlying their dimerization with other RAF family members remain unknown. Here we show that the selective heterodimerization of BRAF with KSR1 is specified by direct contacts between the amino-terminal regulatory regions of each protein, comprising in part a novel domain called BRS in BRAF and the coiled-coil-sterile α motif (CC-SAM) domain in KSR1. We also discovered that MEK binding to the kinase domain of KSR1 asymmetrically drives BRAF-KSR1 heterodimerization, resulting in the concomitant stimulation of BRAF catalytic activity towards free MEK molecules. These findings demonstrate that KSR-MEK complexes allosterically activate BRAF through the action of N-terminal regulatory region and kinase domain contacts and challenge the accepted role of KSR as a scaffold for MEK recruitment to RAF.}, } @article {pmid29433125, year = {2018}, author = {Perez, FF and Fontela, M and García-Ibáñez, MI and Mercier, H and Velo, A and Lherminier, P and Zunino, P and de la Paz, M and Alonso-Pérez, F and Guallart, EF and Padin, XA}, title = {Meridional overturning circulation conveys fast acidification to the deep Atlantic Ocean.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {515-518}, pmid = {29433125}, issn = {1476-4687}, mesh = {Acids/*analysis ; Animals ; Anthozoa/chemistry ; Atlantic Ocean ; Atmosphere/chemistry ; Calcium Carbonate/analysis ; Carbon Dioxide/analysis ; Cold Temperature ; Ecosystem ; Hydrogen-Ion Concentration ; Seawater/*chemistry ; *Water Movements ; }, abstract = {Since the Industrial Revolution, the North Atlantic Ocean has been accumulating anthropogenic carbon dioxide (CO2) and experiencing ocean acidification, that is, an increase in the concentration of hydrogen ions (a reduction in pH) and a reduction in the concentration of carbonate ions. The latter causes the 'aragonite saturation horizon'-below which waters are undersaturated with respect to a particular calcium carbonate, aragonite-to move to shallower depths (to shoal), exposing corals to corrosive waters. Here we use a database analysis to show that the present rate of supply of acidified waters to the deep Atlantic could cause the aragonite saturation horizon to shoal by 1,000-1,700 metres in the subpolar North Atlantic within the next three decades. We find that, during 1991-2016, a decrease in the concentration of carbonate ions in the Irminger Sea caused the aragonite saturation horizon to shoal by about 10-15 metres per year, and the volume of aragonite-saturated waters to reduce concomitantly. Our determination of the transport of the excess of carbonate over aragonite saturation (xc[CO32-])-an indicator of the availability of aragonite to organisms-by the Atlantic meridional overturning circulation shows that the present-day transport of carbonate ions towards the deep ocean is about 44 per cent lower than it was in preindustrial times. We infer that a doubling of atmospheric anthropogenic CO2 levels-which could occur within three decades according to a 'business-as-usual scenario' for climate change-could reduce the transport of xc[CO32-] by 64-79 per cent of that in preindustrial times, which could severely endanger cold-water coral habitats. The Atlantic meridional overturning circulation would also export this acidified deep water southwards, spreading corrosive waters to the world ocean.}, } @article {pmid29432851, year = {2018}, author = {Gates, DJ and Pilson, D and Smith, SD}, title = {Filtering of target sequence capture individuals facilitates species tree construction in the plant subtribe Iochrominae (Solanaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {26-34}, doi = {10.1016/j.ympev.2018.02.002}, pmid = {29432851}, issn = {1095-9513}, mesh = {Base Sequence ; Cluster Analysis ; Databases, Genetic ; High-Throughput Nucleotide Sequencing/methods ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; Solanaceae/*classification/*genetics ; Species Specificity ; }, abstract = {Advances in sequencing technology have made it possible to produce large multi-locus datasets required for species tree analyses. One challenge with constructing high throughput sequencing datasets, however, is that missing information is propagated at different steps in the sequence preparation process. To date, species tree studies have focused on filtering and removing errors that occur at particular loci. Given the way that high throughput sequencing datasets are constructed, however, large amounts of error or ambiguity may also manifest across individuals. Here we use a novel tree-based multivariate clustering method to identify and remove individuals with low phylogenetic signal in a nuclear sequence capture dataset for the Iochrominae clade (Solanaceae). Our results suggest that the low quality tips are the result of the library preparation process (e.g. unequal pooling) rather than poor capture due to phylogenetic distance from the reference species. After implementing the clustering approach and removing low quality tips, we construct an Iochrominae species tree that resolves a number of unknown relationships. We propose this pipeline as a valuable tool for species tree reconstruction with phylogenomic datasets containing variable levels of missing data.}, } @article {pmid29432850, year = {2018}, author = {Fonseca, LHM and Lohmann, LG}, title = {Combining high-throughput sequencing and targeted loci data to infer the phylogeny of the "Adenocalymma-Neojobertia" clade (Bignonieae, Bignoniaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {1-15}, doi = {10.1016/j.ympev.2018.01.023}, pmid = {29432850}, issn = {1095-9513}, mesh = {Bayes Theorem ; Bignoniaceae/anatomy & histology/*classification/*genetics/ultrastructure ; Cell Nucleus/genetics ; Flowers/anatomy & histology ; *Genetic Loci ; High-Throughput Nucleotide Sequencing/*methods ; *Phylogeny ; Plastids/metabolism ; Sequence Analysis, DNA ; }, abstract = {Combining high-throughput sequencing data with amplicon sequences allows the reconstruction of robust phylogenies based on comprehensive sampling of characters and taxa. Here, we combine Next Generation Sequencing (NGS) and Sanger sequencing data to infer the phylogeny of the "Adenocalymma-Neojobertia" clade (Bignonieae, Bignoniaceae), a diverse lineage of Neotropical plants, using Maximum Likelihood and Bayesian approaches. We used NGS to obtain complete or nearly-complete plastomes of members of this clade, leading to a final dataset with 54 individuals, representing 44 members of ingroup and 10 outgroups. In addition, we obtained Sanger sequences of two plastid markers (ndhF and rpl32-trnL) for 44 individuals (43 ingroup and 1 outgroup) and the nuclear PepC for 64 individuals (63 ingroup and 1 outgroup). Our final dataset includes 87 individuals of members of the "Adenocalymma-Neojobertia" clade, representing 66 species (ca. 90% of the diversity), plus 11 outgroups. Plastid and nuclear datasets recovered congruent topologies and were combined. The combined analysis recovered a monophyletic "Adenocalymma-Neojobertia" clade and a paraphyletic Adenocalymma that also contained a monophyletic Neojobertia plus Pleonotoma albiflora. Relationships are strongly supported in all analyses, with most lineages within the "Adenocalymma-Neojobertia" clade receiving maximum posterior probabilities. Ancestral character state reconstructions using Bayesian approaches identified six morphological synapomorphies of clades namely, prophyll type, petiole and petiolule articulation, tendril ramification, inflorescence ramification, calyx shape, and fruit wings. Other characters such as habit, calyx cupular trichomes, corolla color, and corolla shape evolved multiple times. These characters are putatively related with the clade diversification and can be further explored in diversification studies.}, } @article {pmid29432810, year = {2018}, author = {Lo, YL and Chen, CL and Shen, L and Chen, YC and Wang, YH and Lee, CC and Wang, LC and Chuang, CH and Janapatla, RP and Chiu, CH and Chang, HY}, title = {Characterization of the role of global regulator FliA in the pathophysiology of Pseudomonas aeruginosa infection.}, journal = {Research in microbiology}, volume = {169}, number = {3}, pages = {135-144}, doi = {10.1016/j.resmic.2018.02.001}, pmid = {29432810}, issn = {1769-7123}, mesh = {Animals ; Bacterial Proteins/*genetics/metabolism ; Computational Biology/methods ; Gene Expression Profiling ; Gene Expression Regulation, Bacterial ; Mice ; Mutation ; Phenotype ; Pseudomonas Infections/*microbiology ; Pseudomonas aeruginosa/*physiology/ultrastructure ; Sigma Factor/*genetics/metabolism ; Transcription, Genetic ; Transcriptome ; Virulence/genetics ; }, abstract = {FliA is known to be a sigma factor that regulates bacterial flagella gene expression. Accumulating evidence suggests that FliA is involved in bacterial behavior other than motility. To elucidate the contribution of FliA to Pseudomonas aeruginosa pathophysiology, we analyzed the biological properties and gene expression profiles of a ΔfliA mutant. Transcriptome analysis results demonstrated that the expression levels of flagella biogenesis genes decreased dramatically in the mutant; consequently, the ΔfliA mutant failed to synthesize flagella and exhibited reduced motility. The ΔfliA mutant displayed stronger hemolytic and caseinolytic activities, as well as pyocyanin production. The expression of type 6 secretion system-II genes and interbacterial competition activity was decreased in the ΔfliA mutant. Direct evidence of fliA participation in virulence was obtained from analysis of hypervirulent strain B136-33. Adhesion to and cytotoxicity toward mammalian cells and penetration through cell layers were noted; furthermore, the colonization ability of the fliA::Tn5 mutant in the intestines of laboratory mice was compromised. Notably, the fliA-overexpressing strain displayed phenotypes similar to that of the fliA-defective strain, indicating that optimal FliA levels are critical to bacterial physiology. Our findings indicate that FliA plays diverse roles in P. aeruginosa, not only in flagella biosynthesis, but also in pathophysiology.}, } @article {pmid29432584, year = {2018}, author = {Basra, P and Alsaadi, A and Bernal-Astrain, G and O'Sullivan, ML and Hazlett, B and Clarke, LM and Schoenrock, A and Pitre, S and Wong, A}, title = {Fitness tradeoffs of antibiotic resistance in extra-intestinal pathogenic Escherichia coli.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29432584}, issn = {1759-6653}, abstract = {Evolutionary trade-offs occur when selection on one trait has detrimental effects on other traits. In pathogenic microbes, it has been hypothesized that antibiotic resistance trades off with fitness in the absence of antibiotic. While studies of single resistance mutations support this hypothesis, it is unclear whether trade-offs are maintained over time, due to compensatory evolution and broader effects of genetic background. Here, we leverage natural variation in 39 extra-intestinal clinical isolates of Escherichia coli to assess trade-offs between growth rates and resistance to fluoroquinolone and cephalosporin antibiotics. Whole genome sequencing identifies a broad range of clinically relevant resistance determinants in these strains. We find evidence for a negative correlation between growth rate and antibiotic resistance, consistent with a persistent trade-off between resistance and growth. However, this relationship is sometimes weak, and depends on the environment in which growth rates are measured. Using in vitro selection experiments, we find that compensatory evolution in one environment does not guarantee compensation in other environments. Thus, even in the face of compensatory evolution and other genetic background effects, resistance may be broadly costly, supporting the use of drug restriction protocols to limit the spread of resistance. Furthermore, our study demonstrates the power of using natural variation to study evolutionary trade-offs in microbes.}, } @article {pmid29432195, year = {2018}, author = {Papagianni, A and Forés, M and Shao, W and He, S and Koenecke, N and Andreu, MJ and Samper, N and Paroush, Z and González-Crespo, S and Zeitlinger, J and Jiménez, G}, title = {Capicua controls Toll/IL-1 signaling targets independently of RTK regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1807-1812}, pmid = {29432195}, issn = {1091-6490}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Cell Nucleus/genetics/metabolism ; Drosophila/embryology/enzymology/*genetics/metabolism ; Drosophila Proteins/genetics/*metabolism ; Female ; Gene Expression Regulation, Developmental ; HMGB Proteins/genetics/*metabolism ; Male ; Nuclear Proteins/genetics/metabolism ; Phosphoproteins/genetics/metabolism ; Promoter Regions, Genetic ; Receptor Protein-Tyrosine Kinases/genetics/*metabolism ; Repressor Proteins/genetics/*metabolism ; *Signal Transduction ; Toll-Like Receptors/genetics/*metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {The HMG-box protein Capicua (Cic) is a conserved transcriptional repressor that functions downstream of receptor tyrosine kinase (RTK) signaling pathways in a relatively simple switch: In the absence of signaling, Cic represses RTK-responsive genes by binding to nearly invariant sites in DNA, whereas activation of RTK signaling down-regulates Cic activity, leading to derepression of its targets. This mechanism controls gene expression in both Drosophila and mammals, but whether Cic can also function via other regulatory mechanisms remains unknown. Here, we characterize an RTK-independent role of Cic in regulating spatially restricted expression of Toll/IL-1 signaling targets in Drosophila embryogenesis. We show that Cic represses those targets by binding to suboptimal DNA sites of lower affinity than its known consensus sites. This binding depends on Dorsal/NF-κB, which translocates into the nucleus upon Toll activation and binds next to the Cic sites. As a result, Cic binds to and represses Toll targets only in regions with nuclear Dorsal. These results reveal a mode of Cic regulation unrelated to the well-established RTK/Cic depression axis and implicate cooperative binding in conjunction with low-affinity binding sites as an important mechanism of enhancer regulation. Given that Cic plays a role in many developmental and pathological processes in mammals, our results raise the possibility that some of these Cic functions are independent of RTK regulation and may depend on cofactor-assisted DNA binding.}, } @article {pmid29432194, year = {2018}, author = {Li, J and Wu, C and Wang, W and He, Y and Elkayam, E and Joshua-Tor, L and Hammond, PT}, title = {Structurally modulated codelivery of siRNA and Argonaute 2 for enhanced RNA interference.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {E2696-E2705}, pmid = {29432194}, issn = {1091-6490}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Argonaute Proteins/*genetics/metabolism ; Drug Delivery Systems/methods ; Genetic Therapy/*methods ; Melanoma, Experimental/genetics/mortality/therapy ; Mice, Inbred C57BL ; Oncogenes/genetics ; Polyamines/chemistry ; *RNA Interference ; RNA, Antisense/administration & dosage/pharmacology ; RNA, Double-Stranded/administration & dosage/chemistry/genetics ; RNA, Messenger ; RNA, Small Interfering/*administration & dosage/chemistry ; RNA-Induced Silencing Complex/*chemistry/genetics/metabolism ; STAT3 Transcription Factor/genetics ; Structure-Activity Relationship ; Transfection/methods ; }, abstract = {Small interfering RNA (siRNA) represents a promising class of inhibitors in both fundamental research and the clinic. Numerous delivery vehicles have been developed to facilitate siRNA delivery. Nevertheless, achieving highly potent RNA interference (RNAi) toward clinical translation requires efficient formation of RNA-induced gene-silencing complex (RISC) in the cytoplasm. Here we coencapsulate siRNA and the central RNAi effector protein Argonaute 2 (Ago2) via different delivery carriers as a platform to augment RNAi. The physical clustering between siRNA and Ago2 is found to be indispensable for enhanced RNAi. Moreover, by utilizing polyamines bearing the same backbone but distinct cationic side-group arrangements of ethylene diamine repeats as the delivery vehicles, we find that the molecular structure of these polyamines modulates the degree of siRNA/Ago2-mediated improvement of RNAi. We apply this strategy to silence the oncogene STAT3 and significantly prolong survival in mice challenged with melanoma. Our findings suggest a paradigm for RNAi via the synergistic coassembly of RNA with helper proteins.}, } @article {pmid29432193, year = {2018}, author = {Yang, Z and Zhu, T}, title = {Bayesian selection of misspecified models is overconfident and may cause spurious posterior probabilities for phylogenetic trees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1854-1859}, pmid = {29432193}, issn = {1091-6490}, support = {BB/P006493/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Bayes Theorem ; Computer Simulation ; Data Interpretation, Statistical ; *Models, Genetic ; *Phylogeny ; }, abstract = {The Bayesian method is noted to produce spuriously high posterior probabilities for phylogenetic trees in analysis of large datasets, but the precise reasons for this overconfidence are unknown. In general, the performance of Bayesian selection of misspecified models is poorly understood, even though this is of great scientific interest since models are never true in real data analysis. Here we characterize the asymptotic behavior of Bayesian model selection and show that when the competing models are equally wrong, Bayesian model selection exhibits surprising and polarized behaviors in large datasets, supporting one model with full force while rejecting the others. If one model is slightly less wrong than the other, the less wrong model will eventually win when the amount of data increases, but the method may become overconfident before it becomes reliable. We suggest that this extreme behavior may be a major factor for the spuriously high posterior probabilities for evolutionary trees. The philosophical implications of our results to the application of Bayesian model selection to evaluate opposing scientific hypotheses are yet to be explored, as are the behaviors of non-Bayesian methods in similar situations.}, } @article {pmid29432192, year = {2018}, author = {Di Gennaro, A and Araújo, AC and Busch, A and Jin, H and Wågsäter, D and Vorkapic, E and Caidahl, K and Eriksson, P and Samuelsson, B and Maegdefessel, L and Haeggström, JZ}, title = {Cysteinyl leukotriene receptor 1 antagonism prevents experimental abdominal aortic aneurysm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1907-1912}, pmid = {29432192}, issn = {1091-6490}, mesh = {Acetates/*pharmacology ; Angiotensin II/administration & dosage ; Animals ; Aortic Aneurysm, Abdominal/metabolism/*prevention & control ; Chemokine CCL3/metabolism ; *Disease Models, Animal ; Leukotriene Antagonists/*pharmacology ; Matrix Metalloproteinase 9/metabolism ; Mice ; Mice, Knockout, ApoE ; Quinolines/*pharmacology ; Receptors, Leukotriene/genetics/*metabolism ; }, abstract = {Cysteinyl-leukotrienes (cys-LTs) are 5-lipoxygenase-derived lipid mediators involved in the pathogenesis and progression of inflammatory disorders, in particular asthma. We have previously found evidence linking these mediators to increased levels of proteolytic enzymes in tissue specimens of human abdominal aortic aneurysm (AAA). Here we show that antagonism of the CysLT1 receptor by montelukast, an established antiasthma drug, protects against a strong aorta dilatation (>50% increase = aneurysm) in a mouse model of CaCl2-induced AAA at a dose comparable to human medical practice. Analysis of tissue extracts revealed that montelukast reduces the levels of matrix metalloproteinase-9 (MMP-9) and macrophage inflammatory protein-1α (MIP-1α) in the aortic wall. Furthermore, aneurysm progression was specifically mediated through CysLT1 signaling since a selective CysLT2 antagonist was without effect. A significantly reduced vessel dilatation is also observed when treatment with montelukast is started days after aneurysm induction, suggesting that the drug not only prevents but also stops and possibly reverts an already ongoing degenerative process. Moreover, montelukast reduced the incidence of aortic rupture and attenuated the AAA development in two additional independent models, i.e., angiotensin II- and porcine pancreatic elastase-induced AAA, respectively. Our results indicate that cys-LTs are involved in the pathogenesis of AAA and that antagonism of the CysLT1 receptor is a promising strategy for preventive and therapeutic treatment of this clinically silent and highly lethal disease.}, } @article {pmid29432191, year = {2018}, author = {Zhu, X and Guan, Y and Signore, AV and Natarajan, C and DuBay, SG and Cheng, Y and Han, N and Song, G and Qu, Y and Moriyama, H and Hoffmann, FG and Fago, A and Lei, F and Storz, JF}, title = {Divergent and parallel routes of biochemical adaptation in high-altitude passerine birds from the Qinghai-Tibet Plateau.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1865-1870}, pmid = {29432191}, issn = {1091-6490}, support = {R01 HL087216/HL/NHLBI NIH HHS/United States ; }, mesh = {Adaptation, Physiological/*genetics ; *Altitude ; Animal Distribution ; Animals ; Evolution, Molecular ; Hemoglobins/genetics/*physiology ; Models, Molecular ; Passeriformes/blood/*genetics/*physiology ; Protein Conformation ; Protein Isoforms ; Tibet ; }, abstract = {When different species experience similar selection pressures, the probability of evolving similar adaptive solutions may be influenced by legacies of evolutionary history, such as lineage-specific changes in genetic background. Here we test for adaptive convergence in hemoglobin (Hb) function among high-altitude passerine birds that are native to the Qinghai-Tibet Plateau, and we examine whether convergent increases in Hb-O2 affinity have a similar molecular basis in different species. We documented that high-altitude parid and aegithalid species from the Qinghai-Tibet Plateau have evolved derived increases in Hb-O2 affinity in comparison with their closest lowland relatives in East Asia. However, convergent increases in Hb-O2 affinity and convergence in underlying functional mechanisms were seldom attributable to the same amino acid substitutions in different species. Using ancestral protein resurrection and site-directed mutagenesis, we experimentally confirmed two cases in which parallel substitutions contributed to convergent increases in Hb-O2 affinity in codistributed high-altitude species. In one case involving the ground tit (Parus humilis) and gray-crested tit (Lophophanes dichrous), parallel amino acid replacements with affinity-enhancing effects were attributable to nonsynonymous substitutions at a CpG dinucleotide, suggesting a possible role for mutation bias in promoting recurrent changes at the same site. Overall, most altitude-related changes in Hb function were caused by divergent amino acid substitutions, and a select few were caused by parallel substitutions that produced similar phenotypic effects on the divergent genetic backgrounds of different species.}, } @article {pmid29432190, year = {2018}, author = {Vågesjö, E and Öhnstedt, E and Mortier, A and Lofton, H and Huss, F and Proost, P and Roos, S and Phillipson, M}, title = {Accelerated wound healing in mice by on-site production and delivery of CXCL12 by transformed lactic acid bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1895-1900}, pmid = {29432190}, issn = {1091-6490}, mesh = {Animals ; Cell Proliferation ; Chemokine CXCL12/*administration & dosage/*pharmacology ; Gene Expression Regulation ; Genetic Therapy ; Humans ; Lactobacillus reuteri/*genetics/*metabolism ; Macrophages/metabolism ; Mice ; Plasmids ; Skin ; Tissue Culture Techniques ; Transforming Growth Factor beta/metabolism ; *Wound Healing ; Wounds and Injuries/therapy ; }, abstract = {Impaired wound closure is a growing medical problem associated with metabolic diseases and aging. Immune cells play important roles in wound healing by following instructions from the microenvironment. Here, we developed a technology to bioengineer the wound microenvironment and enhance healing abilities of the immune cells. This resulted in strongly accelerated wound healing and was achieved by transforming Lactobacilli with a plasmid encoding CXCL12. CXCL12-delivering bacteria administrated topically to wounds in mice efficiently enhanced wound closure by increasing proliferation of dermal cells and macrophages, and led to increased TGF-β expression in macrophages. Bacteria-produced lactic acid reduced the local pH, which inhibited the peptidase CD26 and consequently enhanced the availability of bioactive CXCL12. Importantly, treatment with CXCL12-delivering Lactobacilli also improved wound closure in mice with hyperglycemia or peripheral ischemia, conditions associated with chronic wounds, and in a human skin wound model. Further, initial safety studies demonstrated that the topically applied transformed bacteria exerted effects restricted to the wound, as neither bacteria nor the chemokine produced could be detected in systemic circulation. Development of drugs accelerating wound healing is limited by the proteolytic nature of wounds. Our technology overcomes this by on-site chemokine production and reduced degradation, which together ensure prolonged chemokine bioavailability that instructed local immune cells and enhanced wound healing.}, } @article {pmid29432189, year = {2018}, author = {Viegas, J}, title = {Profile of Nancy Ip.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1675-1677}, pmid = {29432189}, issn = {1091-6490}, mesh = {Brain/physiology ; History, 20th Century ; History, 21st Century ; Hong Kong ; Nerve Growth Factors/genetics/metabolism ; Neuronal Plasticity ; Neurosciences/*history ; United States ; }, } @article {pmid29432188, year = {2018}, author = {Zhou, X and Chen, Y and Mok, KY and Zhao, Q and Chen, K and Chen, Y and Hardy, J and Li, Y and Fu, AKY and Guo, Q and Ip, NY and , }, title = {Identification of genetic risk factors in the Chinese population implicates a role of immune system in Alzheimer's disease pathogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1697-1706}, pmid = {29432188}, issn = {1091-6490}, support = {082604/2/07/Z//Wellcome Trust/United Kingdom ; N01AG12100/AG/NIA NIH HHS/United States ; 503480//Medical Research Council/United Kingdom ; U24 AG021886/AG/NIA NIH HHS/United States ; U01 AG032984/AG/NIA NIH HHS/United States ; U01 AG024904/AG/NIA NIH HHS/United States ; U01 AG016976/AG/NIA NIH HHS/United States ; R01 HL105756/HL/NHLBI NIH HHS/United States ; //CIHR/Canada ; R01 AG033193/AG/NIA NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Age of Onset ; Aged ; Aged, 80 and over ; Alzheimer Disease/*genetics/immunology/pathology ; Apolipoproteins E/genetics ; Asian Continental Ancestry Group/*genetics ; China ; Cohort Studies ; Female ; *Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Immune System/immunology ; Male ; Middle Aged ; Potassium Channels, Inwardly Rectifying/genetics/immunology ; Risk Factors ; }, abstract = {Alzheimer's disease (AD) is a leading cause of mortality among the elderly. We performed a whole-genome sequencing study of AD in the Chinese population. In addition to the variants identified in or around the APOE locus (sentinel variant rs73052335, P = 1.44 × 10-14), two common variants, GCH1 (rs72713460, P = 4.36 × 10-5) and KCNJ15 (rs928771, P = 3.60 × 10-6), were identified and further verified for their possible risk effects for AD in three small non-Asian AD cohorts. Genotype-phenotype analysis showed that KCNJ15 variant rs928771 affects the onset age of AD, with earlier disease onset in minor allele carriers. In addition, altered expression level of the KCNJ15 transcript can be observed in the blood of AD subjects. Moreover, the risk variants of GCH1 and KCNJ15 are associated with changes in their transcript levels in specific tissues, as well as changes of plasma biomarkers levels in AD subjects. Importantly, network analysis of hippocampus and blood transcriptome datasets suggests that the risk variants in the APOE, GCH1, and KCNJ15 loci might exert their functions through their regulatory effects on immune-related pathways. Taking these data together, we identified common variants of GCH1 and KCNJ15 in the Chinese population that contribute to AD risk. These variants may exert their functional effects through the immune system.}, } @article {pmid29432187, year = {2018}, author = {Brown, JL and Sun, MA and Kassis, JA}, title = {Global changes of H3K27me3 domains and Polycomb group protein distribution in the absence of recruiters Spps or Pho.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1839-E1848}, pmid = {29432187}, issn = {1091-6490}, mesh = {Animals ; DNA-Binding Proteins/genetics/*metabolism ; Drosophila/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Gene Expression Regulation, Developmental ; Gene Expression Regulation, Enzymologic ; Histone Methyltransferases ; Histone-Lysine N-Methyltransferase/genetics/*metabolism ; Histones ; Polycomb Repressive Complex 1/genetics/*metabolism ; Polycomb-Group Proteins/genetics/*metabolism ; Protein Domains ; }, abstract = {Polycomb group (PcG) proteins maintain the silenced state of key developmental genes in animals, but how these proteins are recruited to specific regions of the genome is still poorly understood. In Drosophila, PcG proteins are recruited to Polycomb response elements (PREs) that include combinations of sites for sequence specific DNA binding "PcG recruiters," including Pho, Cg, and Spps. To understand their roles in PcG recruitment, we compared Pho-, Cg-, and Spps-binding sites against H3K27me3 and key PcG proteins by ChIP-seq in wild-type and mutant third instar larvae. H3K27me3 in canonical Polycomb domains is decreased after the reduction of any recruiter. Reduction of Spps and Pho, but not Cg, causes the redistribution of H3K27me3 to heterochromatin. Regions with dramatically depleted H3K27me3 after Spps knockout are usually accompanied by decreased Pho binding, suggesting their cooperative binding. PcG recruiters, the PRC2 component E(z), and the PRC1 components Psc and Ph cobind thousands of active genes outside of H3K27me3 domains. This study demonstrates the importance of distinct PcG recruiters for the establishment of unique Polycomb domains. Different PcG recruiters can act both cooperatively and independently at specific PcG target genes, highlighting the complexity and diversity of PcG recruitment mechanisms.}, } @article {pmid29432186, year = {2018}, author = {van de Bovenkamp, FS and Derksen, NIL and Ooijevaar-de Heer, P and van Schie, KA and Kruithof, S and Berkowska, MA and van der Schoot, CE and IJspeert, H and van der Burg, M and Gils, A and Hafkenscheid, L and Toes, REM and Rombouts, Y and Plomp, R and Wuhrer, M and van Ham, SM and Vidarsson, G and Rispens, T}, title = {Adaptive antibody diversification through N-linked glycosylation of the immunoglobulin variable region.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1901-1906}, pmid = {29432186}, issn = {1091-6490}, mesh = {Antibodies ; Antibodies, Monoclonal ; Antibody Affinity ; Arthritis, Rheumatoid/immunology ; Autoantibodies ; B-Lymphocytes/metabolism ; Glycosylation ; Humans ; Immunoglobulin G/genetics ; Immunoglobulin Variable Region/*genetics ; }, abstract = {A hallmark of B-cell immunity is the generation of a diverse repertoire of antibodies from a limited set of germline V(D)J genes. This repertoire is usually defined in terms of amino acid composition. However, variable domains may also acquire N-linked glycans, a process conditional on the introduction of consensus amino acid motifs (N-glycosylation sites) during somatic hypermutation. High levels of variable domain glycans have been associated with autoantibodies in rheumatoid arthritis, as well as certain follicular lymphomas. However, the role of these glycans in the humoral immune response remains poorly understood. Interestingly, studies have reported both positive and negative effects on antibody affinity. Our aim was to elucidate the role of variable domain glycans during antigen-specific antibody responses. By analyzing B-cell repertoires by next-generation sequencing, we demonstrate that N-glycosylation sites are introduced at positions in which glycans can affect antigen binding as a result of a specific clustering of progenitor glycosylation sites in the germline sequences of variable domain genes. By analyzing multiple human monoclonal and polyclonal (auto)antibody responses, we subsequently show that this process is subject to selection during antigen-specific antibody responses, skewed toward IgG4, and positively contributes to antigen binding. Together, these results highlight a physiological role for variable domain glycosylation as an additional layer of antibody diversification that modulates antigen binding.}, } @article {pmid29432185, year = {2018}, author = {Sanders, MR and Findlay, HE and Booth, PJ}, title = {Lipid bilayer composition modulates the unfolding free energy of a knotted α-helical membrane protein.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1799-E1808}, pmid = {29432185}, issn = {1091-6490}, support = {294342//European Research Council/International ; }, mesh = {Bacterial Proteins/*chemistry ; Lipid Bilayers/*chemistry ; Membrane Proteins/*chemistry ; Models, Molecular ; Protein Conformation ; Protein Denaturation ; *Protein Unfolding ; Thermodynamics ; }, abstract = {α-Helical membrane proteins have eluded investigation of their thermodynamic stability in lipid bilayers. Reversible denaturation curves have enabled some headway in determining unfolding free energies. However, these parameters have been limited to detergent micelles or lipid bicelles, which do not possess the same mechanical properties as lipid bilayers that comprise the basis of natural membranes. We establish reversible unfolding of the membrane transporter LeuT in lipid bilayers, enabling the comparison of apparent unfolding free energies in different lipid compositions. LeuT is a bacterial ortholog of neurotransmitter transporters and contains a knot within its 12-transmembrane helical structure. Urea is used as a denaturant for LeuT in proteoliposomes, resulting in the loss of up to 30% helical structure depending upon the lipid bilayer composition. Urea unfolding of LeuT in liposomes is reversible, with refolding in the bilayer recovering the original helical structure and transport activity. A linear dependence of the unfolding free energy on urea concentration enables the free energy to be extrapolated to zero denaturant. Increasing lipid headgroup charge or chain lateral pressure increases the thermodynamic stability of LeuT. The mechanical and charge properties of the bilayer also affect the ability of urea to denature the protein. Thus, we not only gain insight to the long-sought-after thermodynamic stability of an α-helical protein in a lipid bilayer but also provide a basis for studies of the folding of knotted proteins in a membrane environment.}, } @article {pmid29432184, year = {2018}, author = {Cooper, L}, title = {Profile of Natasha V. Raikhel.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1672-1674}, pmid = {29432184}, issn = {1091-6490}, mesh = {Agglutinins/genetics/metabolism ; Botany/*history ; History, 20th Century ; History, 21st Century ; Plant Proteins/genetics/metabolism ; Plants/genetics/metabolism ; }, } @article {pmid29432183, year = {2018}, author = {Reyna-Llorens, I and Burgess, SJ and Reeves, G and Singh, P and Stevenson, SR and Williams, BP and Stanley, S and Hibberd, JM}, title = {Ancient duons may underpin spatial patterning of gene expression in C4 leaves.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1931-1936}, pmid = {29432183}, issn = {1091-6490}, support = {BB/L014130//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I002243//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Base Sequence ; *Evolution, Molecular ; Gene Expression Regulation, Plant/*physiology ; Magnoliopsida/genetics/*metabolism ; Mutation ; Photosynthesis/*physiology ; Plant Leaves/cytology/*metabolism ; }, abstract = {If the highly efficient C4 photosynthesis pathway could be transferred to crops with the C3 pathway there could be yield gains of up to 50%. It has been proposed that the multiple metabolic and developmental modifications associated with C4 photosynthesis are underpinned by relatively few master regulators that have allowed the evolution of C4 photosynthesis more than 60 times in flowering plants. Here we identify a component of one such regulator that consists of a pair of cis-elements located in coding sequence of multiple genes that are preferentially expressed in bundle sheath cells of C4 leaves. These motifs represent duons as they play a dual role in coding for amino acids as well as controlling the spatial patterning of gene expression associated with the C4 leaf. They act to repress transcription of C4 photosynthesis genes in mesophyll cells. These duons are also present in the C3 model Arabidopsis thaliana, and, in fact, are conserved in all land plants and even some algae that use C3 photosynthesis. C4 photosynthesis therefore appears to have coopted an ancient regulatory code to generate the spatial patterning of gene expression that is a hallmark of C4 photosynthesis. This intragenic transcriptional regulatory sequence could be exploited in the engineering of efficient photosynthesis of crops.}, } @article {pmid29432182, year = {2018}, author = {Thorstad, R and Wolff, P}, title = {A big data analysis of the relationship between future thinking and decision-making.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1740-E1748}, pmid = {29432182}, issn = {1091-6490}, mesh = {*Decision Making ; *Forecasting ; Humans ; Risk-Taking ; Social Media ; *Thinking ; United States ; }, abstract = {We use big data methods to investigate how decision-making might depend on future sightedness (that is, on how far into the future people's thoughts about the future extend). In study 1, we establish a link between future thinking and decision-making at the population level in showing that US states with citizens having relatively far future sightedness, as reflected in their tweets, take fewer risks than citizens in states having relatively near future sightedness. In study 2, we analyze people's tweets to confirm a connection between future sightedness and decision-making at the individual level in showing that people with long future sightedness are more likely to choose larger future rewards over smaller immediate rewards. In study 3, we show that risk taking decreases with increases in future sightedness as reflected in people's tweets. The ability of future sightedness to predict decisions suggests that future sightedness is a relatively stable cognitive characteristic. This implication was supported in an analysis of tweets by over 38,000 people that showed that future sightedness has both state and trait characteristics (study 4). In study 5, we provide evidence for a potential mechanism by which future sightedness can affect decisions in showing that far future sightedness can make the future seem more connected to the present, as reflected in how people refer to the present, past, and future in their tweets over the course of several minutes. Our studies show how big data methods can be applied to naturalistic data to reveal underlying psychological properties and processes.}, } @article {pmid29432181, year = {2018}, author = {Wei, PC and Lee, CS and Du, Z and Schwer, B and Zhang, Y and Kao, J and Zurita, J and Alt, FW}, title = {Three classes of recurrent DNA break clusters in brain progenitors identified by 3D proximity-based break joining assay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1919-1924}, pmid = {29432181}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Brain ; *DNA Breaks, Double-Stranded ; DNA Repair ; Gene Deletion ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Mice ; Neural Stem Cells/metabolism ; RNA Interference ; Translocation, Genetic ; }, abstract = {We recently discovered 27 recurrent DNA double-strand break (DSB) clusters (RDCs) in mouse neural stem/progenitor cells (NSPCs). Most RDCs occurred across long, late-replicating RDC genes and were found only after mild inhibition of DNA replication. RDC genes share intriguing characteristics, including encoding surface proteins that organize brain architecture and neuronal junctions, and are genetically implicated in neuropsychiatric disorders and/or cancers. RDC identification relies on high-throughput genome-wide translocation sequencing (HTGTS), which maps recurrent DSBs based on their translocation to "bait" DSBs in specific chromosomal locations. Cellular heterogeneity in 3D genome organization allowed unequivocal identification of RDCs on 14 different chromosomes using HTGTS baits on three mouse chromosomes. Additional candidate RDCs were also implicated, however, suggesting that some RDCs were missed. To more completely identify RDCs, we exploited our finding that joining of two DSBs occurs more frequently if they lie on the same cis chromosome. Thus, we used CRISPR/Cas9 to introduce specific DSBs into each mouse chromosome in NSPCs that were used as bait for HTGTS libraries. This analysis confirmed all 27 previously identified RDCs and identified many new ones. NSPC RDCs fall into three groups based on length, organization, transcription level, and replication timing of genes within them. While mostly less robust, the largest group of newly defined RDCs share many intriguing characteristics with the original 27. Our findings also revealed RDCs in NSPCs in the absence of induced replication stress, and support the idea that the latter treatment augments an already active endogenous process.}, } @article {pmid29432180, year = {2018}, author = {Pardo-Pastor, C and Rubio-Moscardo, F and Vogel-González, M and Serra, SA and Afthinos, A and Mrkonjic, S and Destaing, O and Abenza, JF and Fernández-Fernández, JM and Trepat, X and Albiges-Rizo, C and Konstantopoulos, K and Valverde, MA}, title = {Piezo2 channel regulates RhoA and actin cytoskeleton to promote cell mechanobiological responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1925-1930}, pmid = {29432180}, issn = {1091-6490}, support = {R01 CA183804/CA/NCI NIH HHS/United States ; R01 GM114675/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/genetics/*metabolism ; Calcium/metabolism ; Cell Line, Tumor ; Cell Movement ; Gene Expression Regulation, Neoplastic ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Ion Channels/genetics/*metabolism ; Mechanotransduction, Cellular/*physiology ; rhoA GTP-Binding Protein/genetics/*metabolism ; }, abstract = {Actin polymerization and assembly into stress fibers (SFs) is central to many cellular processes. However, how SFs form in response to the mechanical interaction of cells with their environment is not fully understood. Here we have identified Piezo2 mechanosensitive cationic channel as a transducer of environmental physical cues into mechanobiological responses. Piezo2 is needed by brain metastatic cells from breast cancer (MDA-MB-231-BrM2) to probe their physical environment as they anchor and pull on their surroundings or when confronted with confined migration through narrow pores. Piezo2-mediated Ca2+ influx activates RhoA to control the formation and orientation of SFs and focal adhesions (FAs). A possible mechanism for the Piezo2-mediated activation of RhoA involves the recruitment of the Fyn kinase to the cell leading edge as well as calpain activation. Knockdown of Piezo2 in BrM2 cells alters SFs, FAs, and nuclear translocation of YAP; a phenotype rescued by overexpression of dominant-positive RhoA or its downstream effector, mDia1. Consequently, hallmarks of cancer invasion and metastasis related to RhoA, actin cytoskeleton, and/or force transmission, such as migration, extracellular matrix degradation, and Serpin B2 secretion, were reduced in cells lacking Piezo2.}, } @article {pmid29432179, year = {2018}, author = {Chen, JK and Lin, WL and Chen, Z and Liu, HW}, title = {PARP-1-dependent recruitment of cold-inducible RNA-binding protein promotes double-strand break repair and genome stability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1759-E1768}, pmid = {29432179}, issn = {1091-6490}, mesh = {Cell Line, Tumor ; DNA Breaks, Double-Stranded ; DNA Repair ; Gene Expression Regulation ; Genomic Instability ; Humans ; Phosphatidylinositol 3-Kinase/metabolism ; Poly (ADP-Ribose) Polymerase-1/chemistry/*metabolism ; RNA-Binding Proteins/chemistry/*metabolism ; }, abstract = {Maintenance of genome integrity is critical for both faithful propagation of genetic information and prevention of mutagenesis induced by various DNA damage events. Here we report cold-inducible RNA-binding protein (CIRBP) as a newly identified key regulator in DNA double-strand break (DSB) repair. On DNA damage, CIRBP temporarily accumulates at the damaged regions and is poly(ADP ribosyl)ated by poly(ADP ribose) polymerase-1 (PARP-1). Its dissociation from the sites of damage may depend on its phosphorylation status as mediated by phosphatidylinositol 3-kinase-related kinases. In the absence of CIRBP, cells showed reduced γH2AX, Rad51, and 53BP1 foci formation. Moreover, CIRBP-depleted cells exhibited impaired homologous recombination, impaired nonhomologous end-joining, increased micronuclei formation, and higher sensitivity to gamma irradiation, demonstrating the active involvement of CIRBP in DSB repair. Furthermore, CIRBP depleted cells exhibited defects in DNA damage-induced chromatin association of the MRN complex (Mre11, Rad50, and NBS1) and ATM kinase. CIRBP depletion also reduced phosphorylation of a variety of ATM substrate proteins and thus impaired the DNA damage response. Taken together, these results reveal a previously unrecognized role for CIRBP in DSB repair.}, } @article {pmid29432178, year = {2018}, author = {Duncan, CDS and Rodríguez-López, M and Ruis, P and Bähler, J and Mata, J}, title = {General amino acid control in fission yeast is regulated by a nonconserved transcription factor, with functions analogous to Gcn4/Atf4.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1829-E1838}, pmid = {29432178}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; BB/N007697/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/M021483/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 095598/Z/11/Z//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acids/*metabolism/pharmacology ; Fungal Proteins/genetics/*metabolism ; Gene Expression Regulation, Fungal/*physiology ; Schizosaccharomyces/*metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Eukaryotes respond to amino acid starvation by enhancing the translation of mRNAs encoding b-ZIP family transcription factors (GCN4 in Saccharomyces cerevisiae and ATF4 in mammals), which launch transcriptional programs to counter this stress. This pathway involves phosphorylation of the eIF2 translation factor by Gcn2-protein kinases and is regulated by upstream ORFs (uORFs) in the GCN4/ATF4 5' leaders. Here, we present evidence that the transcription factors that mediate this response are not evolutionarily conserved. Although cells of the fission yeast Schizosaccharomyces pombe respond transcriptionally to amino acid starvation, they lack clear Gcn4 and Atf4 orthologs. We used ribosome profiling to identify mediators of this response in S. pombe, looking for transcription factors that behave like GCN4 We discovered a transcription factor (Fil1) translationally induced by amino acid starvation in a 5' leader and Gcn2-dependent manner. Like Gcn4, Fil1 is required for the transcriptional response to amino acid starvation, and Gcn4 and Fil1 regulate similar genes. Despite their similarities in regulation, function, and targets, Fil1 and Gcn4 belong to different transcription factor families (GATA and b-ZIP, respectively). Thus, the same functions are performed by nonorthologous proteins under similar regulation. These results highlight the plasticity of transcriptional networks, which maintain conserved principles with nonconserved regulators.}, } @article {pmid29432177, year = {2018}, author = {Zen, A and Brandenburg, JG and Klimeš, J and Tkatchenko, A and Alfè, D and Michaelides, A}, title = {Fast and accurate quantum Monte Carlo for molecular crystals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1724-1729}, pmid = {29432177}, issn = {1091-6490}, abstract = {Computer simulation plays a central role in modern-day materials science. The utility of a given computational approach depends largely on the balance it provides between accuracy and computational cost. Molecular crystals are a class of materials of great technological importance which are challenging for even the most sophisticated ab initio electronic structure theories to accurately describe. This is partly because they are held together by a balance of weak intermolecular forces but also because the primitive cells of molecular crystals are often substantially larger than those of atomic solids. Here, we demonstrate that diffusion quantum Monte Carlo (DMC) delivers subchemical accuracy for a diverse set of molecular crystals at a surprisingly moderate computational cost. As such, we anticipate that DMC can play an important role in understanding and predicting the properties of a large number of molecular crystals, including those built from relatively large molecules which are far beyond reach of other high-accuracy methods.}, } @article {pmid29432176, year = {2018}, author = {Douville, C and Springer, S and Kinde, I and Cohen, JD and Hruban, RH and Lennon, AM and Papadopoulos, N and Kinzler, KW and Vogelstein, B and Karchin, R}, title = {Detection of aneuploidy in patients with cancer through amplification of long interspersed nucleotide elements (LINEs).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1871-1876}, pmid = {29432176}, issn = {1091-6490}, support = {F31 HG007804/HG/NHGRI NIH HHS/United States ; T32 GM007309/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Aneuploidy ; Chromosome Aberrations ; Genetic Predisposition to Disease ; High-Throughput Nucleotide Sequencing ; Humans ; Long Interspersed Nucleotide Elements/*genetics ; Neoplasms/*genetics ; Nucleic Acid Amplification Techniques/methods ; }, abstract = {Aneuploidy is a feature of most cancer cells, and a myriad of approaches have been developed to detect it in clinical samples. We previously described primers that could be used to amplify ∼38,000 unique long interspersed nucleotide elements (LINEs) from throughout the genome. Here we have developed an approach to evaluate the sequencing data obtained from these amplicons. This approach, called Within-Sample AneupLoidy DetectiOn (WALDO), employs supervised machine learning to detect the small changes in multiple chromosome arms that are often present in cancers. We used WALDO to search for chromosome arm gains and losses in 1,677 tumors and in 1,522 liquid biopsies of blood from cancer patients or normal individuals. Aneuploidy was detected in 95% of cancer biopsies and in 22% of liquid biopsies. Using single-nucleotide polymorphisms within the amplified LINEs, WALDO concomitantly assesses allelic imbalances, microsatellite instability, and sample identification. WALDO can be used on samples containing only a few nanograms of DNA and as little as 1% neoplastic content and has a variety of applications in cancer diagnostics and forensic science.}, } @article {pmid29432175, year = {2018}, author = {Moraes, JGN and Behura, SK and Geary, TW and Hansen, PJ and Neibergs, HL and Spencer, TE}, title = {Uterine influences on conceptus development in fertility-classified animals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1749-E1758}, pmid = {29432175}, issn = {1091-6490}, support = {R01 HD072898/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cattle ; *Cattle Diseases ; Embryo Transfer/*veterinary ; Embryonic Development/*physiology ; Endometrium/metabolism/*physiology ; Female ; *Infertility, Female ; Pregnancy ; Pregnancy Rate ; Transcriptome ; }, abstract = {A major unresolved issue is how the uterus influences infertility and subfertility in cattle. Serial embryo transfer was previously used to classify heifers as high-fertile (HF), subfertile (SF), or infertile (IF). To assess pregnancy loss, two in vivo-produced embryos were transferred into HF, SF, and IF heifers on day 7, and pregnancy outcome was assessed on day 17. Pregnancy rate was substantially higher in HF (71%) and SF (90%) than IF (20%) heifers. Elongating conceptuses were about twofold longer in HF than SF heifers. Transcriptional profiling detected relatively few differences in the endometrium of nonpregnant HF, SF, and IF heifers. In contrast, there was a substantial difference in the transcriptome response of the endometrium to pregnancy between HF and SF heifers. Considerable deficiencies in pregnancy-dependent biological pathways associated with extracellular matrix structure and organization as well as cell adhesion were found in the endometrium of SF animals. Distinct gene expression differences were also observed in conceptuses from HF and SF animals, with many of the genes decreased in SF conceptuses known to be embryonic lethal in mice due to defects in embryo and/or placental development. Analyses of biological pathways, key players, and ligand-receptor interactions based on transcriptome data divulged substantial evidence for dysregulation of conceptus-endometrial interactions in SF animals. These results support the ideas that the uterus impacts conceptus survival and programs conceptus development, and ripple effects of dysregulated conceptus-endometrial interactions elicit loss of the postelongation conceptus in SF cattle during the implantation period of pregnancy.}, } @article {pmid29432174, year = {2018}, author = {Zhao, Y and Tyshkovskiy, A and Muñoz-Espín, D and Tian, X and Serrano, M and de Magalhaes, JP and Nevo, E and Gladyshev, VN and Seluanov, A and Gorbunova, V}, title = {Naked mole rats can undergo developmental, oncogene-induced and DNA damage-induced cellular senescence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1801-1806}, pmid = {29432174}, issn = {1091-6490}, support = {DP1 AG047745/AG/NIA NIH HHS/United States ; R01 AG021518/AG/NIA NIH HHS/United States ; R01 AG038004/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; *Cellular Senescence ; *DNA Damage ; Fibroblasts/cytology/metabolism ; Mole Rats/*genetics/*growth & development/metabolism ; *Oncogenes ; Rats ; }, abstract = {Cellular senescence is an important anticancer mechanism that restricts proliferation of damaged or premalignant cells. Cellular senescence also plays an important role in tissue remodeling during development. However, there is a trade-off associated with cellular senescence as senescent cells contribute to aging pathologies. The naked mole rat (NMR) (Heterocephalus glaber) is the longest-lived rodent that is resistant to a variety of age-related diseases. Remarkably, NMRs do not show aging phenotypes until very late stages of their lives. Here, we tested whether NMR cells undergo cellular senescence. We report that the NMR displays developmentally programmed cellular senescence in multiple tissues, including nail bed, skin dermis, hair follicle, and nasopharyngeal cavity. NMR cells also underwent cellular senescence when transfected with oncogenic Ras. In addition, cellular senescence was detected in NMR embryonic and skin fibroblasts subjected to γ-irradiation (IR). However, NMR cells required a higher dose of IR for induction of cellular senescence, and NMR fibroblasts were resistant to IR-induced apoptosis. Gene expression analyses of senescence-related changes demonstrated that, similar to mice, NMR cells up-regulated senescence-associated secretory phenotype genes but displayed more profound down-regulation of DNA metabolism, transcription, and translation than mouse cells. We conclude that the NMR displays the same types of cellular senescence found in a short-lived rodent.}, } @article {pmid29432173, year = {2018}, author = {Muretta, JM and Reddy, BJN and Scarabelli, G and Thompson, AF and Jariwala, S and Major, J and Venere, M and Rich, JN and Willard, B and Thomas, DD and Stumpff, J and Grant, BJ and Gross, SP and Rosenfeld, SS}, title = {A posttranslational modification of the mitotic kinesin Eg5 that enhances its mechanochemical coupling and alters its mitotic function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1779-E1788}, pmid = {29432173}, issn = {1091-6490}, support = {S10 RR031537/RR/NCRR NIH HHS/United States ; R01 NS073610/NS/NINDS NIH HHS/United States ; R01 AR032961/AR/NIAMS NIH HHS/United States ; R01 GM070862/GM/NIGMS NIH HHS/United States ; R01 GM102875/GM/NIGMS NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; R01 GM121491/GM/NIGMS NIH HHS/United States ; R37 AR032961/AR/NIAMS NIH HHS/United States ; R01 GM123068/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Biomechanical Phenomena ; HeLa Cells ; Humans ; Kinesin/*chemistry/*metabolism ; Mitosis/*physiology ; Models, Molecular ; Mutation ; Protein Conformation ; }, abstract = {Numerous posttranslational modifications have been described in kinesins, but their consequences on motor mechanics are largely unknown. We investigated one of these-acetylation of lysine 146 in Eg5-by creating an acetylation mimetic lysine to glutamine substitution (K146Q). Lysine 146 is located in the α2 helix of the motor domain, where it makes an ionic bond with aspartate 91 on the neighboring α1 helix. Molecular dynamics simulations predict that disrupting this bond enhances catalytic site-neck linker coupling. We tested this using structural kinetics and single-molecule mechanics and found that the K146Q mutation increases motor performance under load and coupling of the neck linker to catalytic site. These changes convert Eg5 from a motor that dissociates from the microtubule at low load into one that is more tightly coupled and dissociation resistant-features shared by kinesin 1. These features combined with the increased propensity to stall predict that the K146Q Eg5 acetylation mimetic should act in the cell as a "brake" that slows spindle pole separation, and we have confirmed this by expressing this modified motor in mitotically active cells. Thus, our results illustrate how a posttranslational modification of a kinesin can be used to fine tune motor behavior to meet specific physiological needs.}, } @article {pmid29432172, year = {2018}, author = {Zhao, M and Dervaux, J and Narita, T and Lequeux, F and Limat, L and Roché, M}, title = {Geometrical control of dissipation during the spreading of liquids on soft solids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1748-1753}, pmid = {29432172}, issn = {1091-6490}, abstract = {Gel layers bound to a rigid substrate are used in cell culture to control differentiation and migration and to lower the friction and tailor the wetting of solids. Their thickness, often considered a negligible parameter, affects cell mechanosensing or the shape of sessile droplets. Here, we show that the adjustment of coating thickness provides control over energy dissipation during the spreading of flowing matter on a gel layer. We combine experiments and theory to provide an analytical description of both the statics and the dynamics of the contact line between the gel, the liquid, and the surrounding atmosphere. We extract from this analysis a hitherto-unknown scaling law that predicts the dynamic contact angle between the three phases as a function of the properties of the coating and the velocity of the contact line. Finally, we show that droplets moving on vertical substrates coated with gel layers having linear thickness gradients drift toward regions of higher energy dissipation. Thus, thickness control opens the opportunity to design a priori the path followed by large droplets moving on gel-coated substrates. Our study shows that thickness is another parameter, besides surface energy and substrate mechanics, to tune the dynamics of liquid spreading and wetting on a compliant coating, with potential applications in dew collection and free-surface flow control.}, } @article {pmid29432171, year = {2018}, author = {Zhou, J and Liu, D and Wang, P and Ma, X and Lin, W and Chen, S and Mishev, K and Lu, D and Kumar, R and Vanhoutte, I and Meng, X and He, P and Russinova, E and Shan, L}, title = {Regulation of Arabidopsis brassinosteroid receptor BRI1 endocytosis and degradation by plant U-box PUB12/PUB13-mediated ubiquitination.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1906-E1915}, pmid = {29432171}, issn = {1091-6490}, support = {R01 GM092893/GM/NIGMS NIH HHS/United States ; R01 GM097247/GM/NIGMS NIH HHS/United States ; }, mesh = {Arabidopsis/*enzymology/genetics/metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Brassinosteroids/metabolism ; *Endocytosis ; Protein Kinases/genetics/*metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases/genetics/*metabolism ; Ubiquitination ; }, abstract = {Plants largely rely on plasma membrane (PM)-resident receptor-like kinases (RLKs) to sense extracellular and intracellular stimuli and coordinate cell differentiation, growth, and immunity. Several RLKs have been shown to undergo internalization through the endocytic pathway with a poorly understood mechanism. Here, we show that endocytosis and protein abundance of the Arabidopsis brassinosteroid (BR) receptor, BR INSENSITIVE1 (BRI1), are regulated by plant U-box (PUB) E3 ubiquitin ligase PUB12- and PUB13-mediated ubiquitination. BR perception promotes BRI1 ubiquitination and association with PUB12 and PUB13 through phosphorylation at serine 344 residue. Loss of PUB12 and PUB13 results in reduced BRI1 ubiquitination and internalization accompanied with a prolonged BRI1 PM-residence time, indicating that ubiquitination of BRI1 by PUB12 and PUB13 is a key step in BRI1 endocytosis. Our studies provide a molecular link between BRI1 ubiquitination and internalization and reveal a unique mechanism of E3 ligase-substrate association regulated by phosphorylation.}, } @article {pmid29432170, year = {2018}, author = {Fu, TM and Shen, C and Li, Q and Zhang, P and Wu, H}, title = {Mechanism of ubiquitin transfer promoted by TRAF6.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1783-1788}, pmid = {29432170}, issn = {1091-6490}, support = {DP1 HD087988/HD/NICHD NIH HHS/United States ; R01 AI050872/AI/NIAID NIH HHS/United States ; R37 AI050872/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Animals ; Dimerization ; Mice ; Protein Binding ; Protein Domains ; TNF Receptor-Associated Factor 6/chemistry/genetics/*metabolism ; Ubiquitin/chemistry/*metabolism ; Ubiquitin-Conjugating Enzymes/genetics/metabolism ; Ubiquitination ; }, abstract = {Tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6) plays a vital role in immune signal transduction pathways by acting as a ubiquitin ligase (E3) for Lys63-linked polyubiquitin chain synthesis. However, the detailed mechanism by which the TRAF6 RING dimer promotes ubiquitin transfer was unknown. Through structural modeling and biochemical analysis, we here show that the TRAF6 RING dimer employs a concerted allosteric mechanism using both subunits of the TRAF6 dimer to promote ubiquitin (Ub) transfer. In particular, we reveal the importance of the C-terminal extension of the TRAF6 RING domain that mediates trans-interactions with the donor-Ub. By analyzing structures and models of E3s in complex with Ub-loaded ubiquitin-conjugating enzymes (E2s), we further highlight the roles of N-terminal and C-terminal extensions beyond the bona fide RING domains in promoting Ub transfer through engagement with a donor-Ub in cis and in trans, respectively.}, } @article {pmid29432169, year = {2018}, author = {Kozłowska, M and Brudzinski, MR and Friberg, P and Skoumal, RJ and Baxter, ND and Currie, BS}, title = {Maturity of nearby faults influences seismic hazard from hydraulic fracturing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1720-E1729}, pmid = {29432169}, issn = {1091-6490}, abstract = {Understanding the causes of human-induced earthquakes is paramount to reducing societal risk. We investigated five cases of seismicity associated with hydraulic fracturing (HF) in Ohio since 2013 that, because of their isolation from other injection activities, provide an ideal setting for studying the relations between high-pressure injection and earthquakes. Our analysis revealed two distinct groups: (i) deeper earthquakes in the Precambrian basement, with larger magnitudes (M > 2), b-values < 1, and many post-shut-in earthquakes, versus (ii) shallower earthquakes in Paleozoic rocks ∼400 m below HF, with smaller magnitudes (M < 1), b-values > 1.5, and few post-shut-in earthquakes. Based on geologic history, laboratory experiments, and fault modeling, we interpret the deep seismicity as slip on more mature faults in older crystalline rocks and the shallow seismicity as slip on immature faults in younger sedimentary rocks. This suggests that HF inducing deeper seismicity may pose higher seismic hazards. Wells inducing deeper seismicity produced more water than wells with shallow seismicity, indicating more extensive hydrologic connections outside the target formation, consistent with pore pressure diffusion influencing seismicity. However, for both groups, the 2 to 3 h between onset of HF and seismicity is too short for typical fluid pressure diffusion rates across distances of ∼1 km and argues for poroelastic stress transfer also having a primary influence on seismicity.}, } @article {pmid29432168, year = {2018}, author = {}, title = {Correction for Das, Unfounded assumptions in linking crop-damaging temperature and suicide in India.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1699}, doi = {10.1073/pnas.1801218115}, pmid = {29432168}, issn = {1091-6490}, } @article {pmid29432167, year = {2018}, author = {Slik, JWF and Franklin, J and Arroyo-Rodríguez, V and Field, R and Aguilar, S and Aguirre, N and Ahumada, J and Aiba, SI and Alves, LF and K, A and Avella, A and Mora, F and Aymard C, GA and Báez, S and Balvanera, P and Bastian, ML and Bastin, JF and Bellingham, PJ and van den Berg, E and da Conceição Bispo, P and Boeckx, P and Boehning-Gaese, K and Bongers, F and Boyle, B and Brambach, F and Brearley, FQ and Brown, S and Chai, SL and Chazdon, RL and Chen, S and Chhang, P and Chuyong, G and Ewango, C and Coronado, IM and Cristóbal-Azkarate, J and Culmsee, H and Damas, K and Dattaraja, HS and Davidar, P and DeWalt, SJ and Din, H and Drake, DR and Duque, A and Durigan, G and Eichhorn, K and Eler, ES and Enoki, T and Ensslin, A and Fandohan, AB and Farwig, N and Feeley, KJ and Fischer, M and Forshed, O and Garcia, QS and Garkoti, SC and Gillespie, TW and Gillet, JF and Gonmadje, C and Granzow-de la Cerda, I and Griffith, DM and Grogan, J and Hakeem, KR and Harris, DJ and Harrison, RD and Hector, A and Hemp, A and Homeier, J and Hussain, MS and Ibarra-Manríquez, G and Hanum, IF and Imai, N and Jansen, PA and Joly, CA and Joseph, S and Kartawinata, K and Kearsley, E and Kelly, DL and Kessler, M and Killeen, TJ and Kooyman, RM and Laumonier, Y and Laurance, SG and Laurance, WF and Lawes, MJ and Letcher, SG and Lindsell, J and Lovett, J and Lozada, J and Lu, X and Lykke, AM and Mahmud, KB and Mahayani, NPD and Mansor, A and Marshall, AR and Martin, EH and Calderado Leal Matos, D and Meave, JA and Melo, FPL and Mendoza, ZHA and Metali, F and Medjibe, VP and Metzger, JP and Metzker, T and Mohandass, D and Munguía-Rosas, MA and Muñoz, R and Nurtjahy, E and de Oliveira, EL and Onrizal, and Parolin, P and Parren, M and Parthasarathy, N and Paudel, E and Perez, R and Pérez-García, EA and Pommer, U and Poorter, L and Qie, L and Piedade, MTF and Pinto, JRR and Poulsen, AD and Poulsen, JR and Powers, JS and Prasad, RC and Puyravaud, JP and Rangel, O and Reitsma, J and Rocha, DSB and Rolim, S and Rovero, F and Rozak, A and Ruokolainen, K and Rutishauser, E and Rutten, G and Mohd Said, MN and Saiter, FZ and Saner, P and Santos, B and Dos Santos, JR and Sarker, SK and Schmitt, CB and Schoengart, J and Schulze, M and Sheil, D and Sist, P and Souza, AF and Spironello, WR and Sposito, T and Steinmetz, R and Stevart, T and Suganuma, MS and Sukri, R and Sultana, A and Sukumar, R and Sunderland, T and Supriyadi, and Suresh, HS and Suzuki, E and Tabarelli, M and Tang, J and Tanner, EVJ and Targhetta, N and Theilade, I and Thomas, D and Timberlake, J and de Morisson Valeriano, M and van Valkenburg, J and Van Do, T and Van Sam, H and Vandermeer, JH and Verbeeck, H and Vetaas, OR and Adekunle, V and Vieira, SA and Webb, CO and Webb, EL and Whitfeld, T and Wich, S and Williams, J and Wiser, S and Wittmann, F and Yang, X and Adou Yao, CY and Yap, SL and Zahawi, RA and Zakaria, R and Zang, R}, title = {Phylogenetic classification of the world's tropical forests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1837-1842}, pmid = {29432167}, issn = {1091-6490}, mesh = {Biodiversity ; Conservation of Natural Resources ; Environmental Monitoring ; *Forests ; *Phylogeny ; Plants/*classification/*genetics ; *Tropical Climate ; }, abstract = {Knowledge about the biogeographic affinities of the world's tropical forests helps to better understand regional differences in forest structure, diversity, composition, and dynamics. Such understanding will enable anticipation of region-specific responses to global environmental change. Modern phylogenies, in combination with broad coverage of species inventory data, now allow for global biogeographic analyses that take species evolutionary distance into account. Here we present a classification of the world's tropical forests based on their phylogenetic similarity. We identify five principal floristic regions and their floristic relationships: (i) Indo-Pacific, (ii) Subtropical, (iii) African, (iv) American, and (v) Dry forests. Our results do not support the traditional neo- versus paleotropical forest division but instead separate the combined American and African forests from their Indo-Pacific counterparts. We also find indications for the existence of a global dry forest region, with representatives in America, Africa, Madagascar, and India. Additionally, a northern-hemisphere Subtropical forest region was identified with representatives in Asia and America, providing support for a link between Asian and American northern-hemisphere forests.}, } @article {pmid29432166, year = {2018}, author = {Palmer, S and Albergante, L and Blackburn, CC and Newman, TJ}, title = {Thymic involution and rising disease incidence with age.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1883-1888}, pmid = {29432166}, issn = {1091-6490}, support = {//Medical Research Council/United Kingdom ; }, mesh = {Aging/*immunology ; Female ; Genetic Predisposition to Disease ; Humans ; Male ; Models, Biological ; Mutation ; Neoplasms/*etiology/*genetics ; Thymus Gland/*physiology ; }, abstract = {For many cancer types, incidence rises rapidly with age as an apparent power law, supporting the idea that cancer is caused by a gradual accumulation of genetic mutations. Similarly, the incidence of many infectious diseases strongly increases with age. Here, combining data from immunology and epidemiology, we show that many of these dramatic age-related increases in incidence can be modeled based on immune system decline, rather than mutation accumulation. In humans, the thymus atrophies from infancy, resulting in an exponential decline in T cell production with a half-life of ∼16 years, which we use as the basis for a minimal mathematical model of disease incidence. Our model outperforms the power law model with the same number of fitting parameters in describing cancer incidence data across a wide spectrum of different cancers, and provides excellent fits to infectious disease data. This framework provides mechanistic insight into cancer emergence, suggesting that age-related decline in T cell output is a major risk factor.}, } @article {pmid29432165, year = {2018}, author = {Zhou, X and Liao, H and Chern, M and Yin, J and Chen, Y and Wang, J and Zhu, X and Chen, Z and Yuan, C and Zhao, W and Wang, J and Li, W and He, M and Ma, B and Wang, J and Qin, P and Chen, W and Wang, Y and Liu, J and Qian, Y and Wang, W and Wu, X and Li, P and Zhu, L and Li, S and Ronald, PC and Chen, X}, title = {Loss of function of a rice TPR-domain RNA-binding protein confers broad-spectrum disease resistance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {12}, pages = {3174-3179}, pmid = {29432165}, issn = {1091-6490}, support = {R01 GM122968/GM/NIGMS NIH HHS/United States ; }, mesh = {Cytoplasm/metabolism ; Disease Resistance/genetics ; Gene Expression Regulation, Plant ; Magnaporthe/pathogenicity ; Mutation ; Oryza/genetics/microbiology/*physiology ; Plant Diseases/*genetics/microbiology ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified/genetics ; Protein Domains ; RNA, Messenger/metabolism ; RNA-Binding Proteins/*genetics/metabolism ; Repetitive Sequences, Amino Acid ; Xanthomonas/pathogenicity ; }, abstract = {Crops carrying broad-spectrum resistance loci provide an effective strategy for controlling infectious disease because these loci typically confer resistance to diverse races of a pathogen or even multiple species of pathogens. Despite their importance, only a few crop broad-spectrum resistance loci have been reported. Here, we report the identification and characterization of the rice bsr-k1 (broad-spectrum resistance Kitaake-1) mutant, which confers broad-spectrum resistance against Magnaporthe oryzae and Xanthomonas oryzae pv oryzae with no major penalty on key agronomic traits. Map-based cloning reveals that Bsr-k1 encodes a tetratricopeptide repeats (TPRs)-containing protein, which binds to mRNAs of multiple OsPAL (OsPAL1-7) genes and promotes their turnover. Loss of function of the Bsr-k1 gene leads to accumulation of OsPAL1-7 mRNAs in the bsr-k1 mutant. Furthermore, overexpression of OsPAL1 in wild-type rice TP309 confers resistance to M. oryzae, supporting the role of OsPAL1 Our discovery of the bsr-k1 allele constitutes a significant conceptual advancement and provides a valuable tool for breeding broad-spectrum resistant rice.}, } @article {pmid29432164, year = {2018}, author = {}, title = {Correction for Murari et al., Climate change and agricultural suicides in India.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1698}, doi = {10.1073/pnas.1801217115}, pmid = {29432164}, issn = {1091-6490}, } @article {pmid29432163, year = {2018}, author = {Aranguren, B and Revedin, A and Amico, N and Cavulli, F and Giachi, G and Grimaldi, S and Macchioni, N and Santaniello, F}, title = {Wooden tools and fire technology in the early Neanderthal site of Poggetti Vecchi (Italy).}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2054-2059}, pmid = {29432163}, issn = {1091-6490}, abstract = {Excavations for the construction of thermal pools at Poggetti Vecchi (Grosseto, Tuscany, central Italy) exposed a series of wooden tools in an open-air stratified site referable to late Middle Pleistocene. The wooden artifacts were uncovered, together with stone tools and fossil bones, largely belonging to the straight-tusked elephant Paleoloxodon antiquus The site is radiometrically dated to around 171,000 y B.P., and hence correlated with the early marine isotope stage 6 [Benvenuti M, et al. (2017) Quat Res 88:327-344]. The sticks, all fragmentary, are made from boxwood (Buxus sempervirens) and were over 1 m long, rounded at one end and pointed at the other. They have been partially charred, possibly to lessen the labor of scraping boxwood, using a technique so far not documented at the time. The wooden artifacts have the size and features of multipurpose tools known as "digging sticks," which are quite commonly used by foragers. This discovery from Poggetti Vecchi provides evidence of the processing and use of wood by early Neanderthals, showing their ability to use fire in tool making from very tough wood.}, } @article {pmid29432162, year = {2018}, author = {Kono, Y and Shibazaki, Y and Kenney-Benson, C and Wang, Y and Shen, G}, title = {Pressure-induced structural change in MgSiO3 glass at pressures near the Earth's core-mantle boundary.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1742-1747}, pmid = {29432162}, issn = {1091-6490}, abstract = {Knowledge of the structure and properties of silicate magma under extreme pressure plays an important role in understanding the nature and evolution of Earth's deep interior. Here we report the structure of MgSiO3 glass, considered an analog of silicate melts, up to 111 GPa. The first (r1) and second (r2) neighbor distances in the pair distribution function change rapidly, with r1 increasing and r2 decreasing with pressure. At 53-62 GPa, the observed r1 and r2 distances are similar to the Si-O and Si-Si distances, respectively, of crystalline MgSiO3 akimotoite with edge-sharing SiO6 structural motifs. Above 62 GPa, r1 decreases, and r2 remains constant, with increasing pressure until 88 GPa. Above this pressure, r1 remains more or less constant, and r2 begins decreasing again. These observations suggest an ultrahigh-pressure structural change around 88 GPa. The structure above 88 GPa is interpreted as having the closest edge-shared SiO6 structural motifs similar to those of the crystalline postperovskite, with densely packed oxygen atoms. The pressure of the structural change is broadly consistent with or slightly lower than that of the bridgmanite-to-postperovskite transition in crystalline MgSiO3 These results suggest that a structural change may occur in MgSiO3 melt under pressure conditions corresponding to the deep lower mantle.}, } @article {pmid29432161, year = {2018}, author = {Li, Z and Hu, B and Wu, Y and Fei, C and Deng, L}, title = {Control of chemoselectivity in asymmetric tandem reactions: Direct synthesis of chiral amines bearing nonadjacent stereocenters.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1730-1735}, pmid = {29432161}, issn = {1091-6490}, support = {R01 GM061591/GM/NIGMS NIH HHS/United States ; }, mesh = {Amines/*chemistry ; Catalysis ; Imines/chemistry ; Molecular Structure ; Phenol/chemistry ; Stereoisomerism ; }, abstract = {This paper describes the mechanistic insight-guided development of a catalyst system, employing a phenolic proton donor catalyst in addition to a cinchonium-derived phase-transfer catalyst, to control the chemoselectivity of two distinct intermediates, thereby enabling the desired asymmetric tandem conjugate addition-protonation pathway to dominate over a number of side-reaction pathways to provide a synthetic approach for the direct generation of optically active amines bearing two nonadjacent stereocenters.}, } @article {pmid29432160, year = {2018}, author = {Fahl, SP and Coffey, F and Kain, L and Zarin, P and Dunbrack, RL and Teyton, L and Zúñiga-Pflücker, JC and Kappes, DJ and Wiest, DL}, title = {Role of a selecting ligand in shaping the murine γδ-TCR repertoire.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1889-1894}, pmid = {29432160}, issn = {1091-6490}, support = {F32 AI120541/AI/NIAID NIH HHS/United States ; F32 AI098241/AI/NIAID NIH HHS/United States ; P01 AI102853/AI/NIAID NIH HHS/United States ; MOP-42387//CIHR/Canada ; R01 GM084453/GM/NIGMS NIH HHS/United States ; P30 CA006927/CA/NCI NIH HHS/United States ; T32 CA009035/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Lineage ; Ligands ; Mice ; Protein Binding ; Receptors, Antigen, T-Cell, gamma-delta/genetics/*metabolism ; T-Lymphocyte Subsets/*physiology ; }, abstract = {Unlike αβ-T lineage cells, where the role of ligand in intrathymic selection is well established, the role of ligand in the development of γδ-T cells remains controversial. Here we provide evidence for the role of a bona fide selecting ligand in shaping the γδ-T cell-receptor (TCR) repertoire. Reactivity of the γδ-TCR with the major histocompatibility complex (MHC) Class Ib ligands, H2-T10/22, is critically dependent upon the EGYEL motif in the complementarity determining region 3 (CDR3) of TCRδ. In the absence of H2-T10/22 ligand, the commitment of H2-T10/22 reactive γδ-T cells to the γδ fate is diminished, and the specification of those γδ committed cells to the IFN-γ or interleukin-17 effector fate is altered. Furthermore, those cells that do adopt the γδ fate and mature exhibit a profound alteration in the γδTCR repertoire, including depletion of the EGYEL motif and reductions in both CDR3δ length and charge. Taken together, these data suggest that ligand plays an important role in shaping the TCR repertoire of γδ-T cells.}, } @article {pmid29432159, year = {2018}, author = {Hou, Y and Lautrup, S and Cordonnier, S and Wang, Y and Croteau, DL and Zavala, E and Zhang, Y and Moritoh, K and O'Connell, JF and Baptiste, BA and Stevnsner, TV and Mattson, MP and Bohr, VA}, title = {NAD+ supplementation normalizes key Alzheimer's features and DNA damage responses in a new AD mouse model with introduced DNA repair deficiency.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1876-E1885}, pmid = {29432159}, issn = {1091-6490}, mesh = {*Alzheimer Disease ; Animals ; Cognitive Dysfunction ; DNA Damage ; *Disease Models, Animal ; Gene Expression Regulation/drug effects ; Male ; Mice ; Mice, Transgenic ; NAD/*pharmacology ; Neurogenesis/drug effects ; Niacinamide/*analogs & derivatives/pharmacology ; Sirtuin 3/genetics/metabolism ; Sirtuins/genetics/metabolism ; tau Proteins/metabolism ; }, abstract = {Emerging findings suggest that compromised cellular bioenergetics and DNA repair contribute to the pathogenesis of Alzheimer's disease (AD), but their role in disease-defining pathology is unclear. We developed a DNA repair-deficient 3xTgAD/Polβ+/- mouse that exacerbates major features of human AD including phosphorylated Tau (pTau) pathologies, synaptic dysfunction, neuronal death, and cognitive impairment. Here we report that 3xTgAD/Polβ+/- mice have a reduced cerebral NAD+/NADH ratio indicating impaired cerebral energy metabolism, which is normalized by nicotinamide riboside (NR) treatment. NR lessened pTau pathology in both 3xTgAD and 3xTgAD/Polβ+/- mice but had no impact on amyloid β peptide (Aβ) accumulation. NR-treated 3xTgAD/Polβ+/- mice exhibited reduced DNA damage, neuroinflammation, and apoptosis of hippocampal neurons and increased activity of SIRT3 in the brain. NR improved cognitive function in multiple behavioral tests and restored hippocampal synaptic plasticity in 3xTgAD mice and 3xTgAD/Polβ+/- mice. In general, the deficits between genotypes and the benefits of NR were greater in 3xTgAD/Polβ+/- mice than in 3xTgAD mice. Our findings suggest a pivotal role for cellular NAD+ depletion upstream of neuroinflammation, pTau, DNA damage, synaptic dysfunction, and neuronal degeneration in AD. Interventions that bolster neuronal NAD+ levels therefore have therapeutic potential for AD.}, } @article {pmid29432158, year = {2018}, author = {Haller, M and Au, J and O'Neill, M and Lamb, DJ}, title = {16p11.2 transcription factor MAZ is a dosage-sensitive regulator of genitourinary development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1849-E1858}, pmid = {29432158}, issn = {1091-6490}, support = {T32 DK007763/DK/NIDDK NIH HHS/United States ; R01 DK078121/DK/NIDDK NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; R25 GM056929/GM/NIGMS NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Cell Adhesion ; Chromosomes, Human, Pair 16 ; DNA-Binding Proteins/genetics/*metabolism ; Gene Deletion ; Gene Expression Regulation, Developmental ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Male ; Mice ; Promoter Regions, Genetic ; RNA Interference ; RNA, Small Interfering ; Transcription Factors/genetics/*metabolism ; Transcription, Genetic ; Urinary Bladder/*abnormalities ; Urogenital Abnormalities/*genetics/pathology ; }, abstract = {Genitourinary (GU) birth defects are among the most common yet least studied congenital malformations. Congenital anomalies of the kidney and urinary tract (CAKUTs) have high morbidity and mortality rates and account for ∼30% of structural birth defects. Copy number variation (CNV) mapping revealed that 16p11.2 is a hotspot for GU development. The only gene covered collectively by all of the mapped GU-patient CNVs was MYC-associated zinc finger transcription factor (MAZ), and MAZ CNV frequency is enriched in nonsyndromic GU-abnormal patients. Knockdown of MAZ in HEK293 cells results in differential expression of several WNT morphogens required for normal GU development, including Wnt11 and Wnt4. MAZ knockdown also prevents efficient transition into S phase, affects transcription of cell-cycle regulators, and abrogates growth of human embryonic kidney cells. Murine Maz is ubiquitously expressed, and a CRISPR-Cas9 mouse model of Maz deletion results in perinatal lethality with survival rates dependent on Maz copy number. Homozygous loss of Maz results in high penetrance of CAKUTs, and Maz is haploinsufficient for normal bladder development. MAZ, once thought to be a simple housekeeping gene, encodes a dosage-sensitive transcription factor that regulates urogenital development and contributes to both nonsyndromic congenital malformations of the GU tract as well as the 16p11.2 phenotype.}, } @article {pmid29432157, year = {2018}, author = {Cheney, DL and Seyfarth, RM}, title = {Flexible usage and social function in primate vocalizations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1974-1979}, pmid = {29432157}, issn = {1091-6490}, mesh = {Animals ; Cognition ; Longevity ; Primates/*physiology ; *Social Behavior ; *Vocalization, Animal ; }, abstract = {Vocalizations are a pervasive feature of nonhuman primate social life, yet we know surprisingly little about their function. We review studies supporting the hypothesis that many primate vocalizations function to facilitate social interactions by reducing uncertainty about the signaler's intentions and likely behavior. Such interactions help to establish and maintain the social bonds that increase reproductive success. Compared with humans, songbirds, and a few other mammals, primates have small vocal repertoires that show little acoustic modification during development. However, their ability to modify call usage is extensive and tuned to variation in the social context, including the historical relationship between caller and listener and the caller's assessment of how a listener is likely to respond. We suggest parallels between the decision to vocalize and neurophysiological studies of other, nonvocal social decisions between interacting monkeys. The selective factors driving the early stages of language evolution may have come from the need to make decisions about when and how to call within the context of social challenges.}, } @article {pmid29432156, year = {2018}, author = {Sitry-Shevah, D and Kaisari, S and Teichner, A and Miniowitz-Shemtov, S and Hershko, A}, title = {Role of ubiquitylation of components of mitotic checkpoint complex in their dissociation from anaphase-promoting complex/cyclosome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1777-1782}, pmid = {29432156}, issn = {1091-6490}, mesh = {*Anaphase ; Anaphase-Promoting Complex-Cyclosome/genetics/*metabolism ; Cdc20 Proteins/genetics/metabolism ; Cell Cycle Proteins/genetics/metabolism ; HeLa Cells ; Humans ; Mad2 Proteins/genetics/metabolism ; Mitosis ; Poly-ADP-Ribose Binding Proteins/genetics/metabolism ; Protein Binding ; Spindle Apparatus/genetics/metabolism ; Ubiquitination ; }, abstract = {The mitotic checkpoint system ensures the fidelity of chromosome segregation in mitosis by preventing premature initiation of anaphase until correct bipolar attachment of chromosomes to the mitotic spindle is reached. It promotes the assembly of a mitotic checkpoint complex (MCC), composed of BubR1, Bub3, Cdc20, and Mad2, which inhibits the activity of the anaphase-promoting complex/cyclosome (APC/C) ubiquitin ligase. When the checkpoint is satisfied, anaphase is initiated by the disassembly of MCC. Previous studies indicated that the dissociation of APC/C-bound MCC requires ubiquitylation and suggested that the target of ubiquitylation is the Cdc20 component of MCC. However, it remained unknown how ubiquitylation causes the release of MCC from APC/C and its disassembly and whether ubiquitylation of additional proteins is involved in this process. We find that ubiquitylation causes the dissociation of BubR1 from Cdc20 in MCC and suggest that this may lead to the release of MCC components from APC/C. BubR1 in MCC is ubiquitylated by APC/C, although to a lesser degree than Cdc20. The extent of BubR1 ubiquitylation was markedly increased in recombinant MCC that contained a lysine-less mutant of Cdc20. Mutation of lysine residues to arginines in the N-terminal region of BubR1 partially inhibited its ubiquitylation and slowed down the release of MCC from APC/C, provided that Cdc20 ubiquitylation was also blocked. It is suggested that ubiquitylation of both Cdc20 and BubR1 may be involved in their dissociation from each other and in the release of MCC components from APC/C.}, } @article {pmid29432155, year = {2018}, author = {Wang, J and Symul, L and Yeung, J and Gobet, C and Sobel, J and Lück, S and Westermark, PO and Molina, N and Naef, F}, title = {Circadian clock-dependent and -independent posttranscriptional regulation underlies temporal mRNA accumulation in mouse liver.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1916-E1925}, pmid = {29432155}, issn = {1091-6490}, mesh = {Animals ; *Circadian Clocks ; *Gene Expression Regulation ; Liver/*metabolism ; Male ; Mice/*genetics/metabolism ; Mice, Inbred C57BL ; Promoter Regions, Genetic ; RNA, Messenger/*genetics/metabolism ; Transcription, Genetic ; }, abstract = {The mammalian circadian clock coordinates physiology with environmental cycles through the regulation of daily oscillations of gene expression. Thousands of transcripts exhibit rhythmic accumulations across mouse tissues, as determined by the balance of their synthesis and degradation. While diurnally rhythmic transcription regulation is well studied and often thought to be the main factor generating rhythmic mRNA accumulation, the extent of rhythmic posttranscriptional regulation is debated, and the kinetic parameters (e.g., half-lives), as well as the underlying regulators (e.g., mRNA-binding proteins) are relatively unexplored. Here, we developed a quantitative model for cyclic accumulations of pre-mRNA and mRNA from total RNA-seq data, and applied it to mouse liver. This allowed us to identify that about 20% of mRNA rhythms were driven by rhythmic mRNA degradation, and another 15% of mRNAs regulated by both rhythmic transcription and mRNA degradation. The method could also estimate mRNA half-lives and processing times in intact mouse liver. We then showed that, depending on mRNA half-life, rhythmic mRNA degradation can either amplify or tune phases of mRNA rhythms. By comparing mRNA rhythms in wild-type and Bmal1-/- animals, we found that the rhythmic degradation of many transcripts did not depend on a functional BMAL1. Interestingly clock-dependent and -independent degradation rhythms peaked at distinct times of day. We further predicted mRNA-binding proteins (mRBPs) that were implicated in the posttranscriptional regulation of mRNAs, either through stabilizing or destabilizing activities. Together, our results demonstrate how posttranscriptional regulation temporally shapes rhythmic mRNA accumulation in mouse liver.}, } @article {pmid29432154, year = {2018}, author = {Müller, F and Cunningham, T and Stookey, S and Tai, CH and Burkett, S and Jailwala, P and Stetler Stevenson, M and Cam, MC and Wayne, AS and Pastan, I}, title = {5-Azacytidine prevents relapse and produces long-term complete remissions in leukemia xenografts treated with Moxetumomab pasudotox.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1867-E1875}, pmid = {29432154}, issn = {1091-6490}, support = {P30 CA014089/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antineoplastic Agents/administration & dosage/therapeutic use ; Azacitidine/administration & dosage/*therapeutic use ; Bacterial Toxins/administration & dosage/*therapeutic use ; Bone Marrow ; Cell Line, Tumor ; Down-Regulation ; Drug Resistance, Neoplasm ; Exotoxins/administration & dosage/*therapeutic use ; Humans ; Leukemia ; Mice ; Neoplasms, Experimental ; Precursor Cell Lymphoblastic Leukemia-Lymphoma ; Recurrence ; }, abstract = {Moxetumomab pasudotox (Moxe) is a chimeric protein composed of an anti-CD22 Fv fused to a portion of Pseudomonas exotoxin A and kills CD22-expressing leukemia cells. It is very active in hairy-cell leukemia, but many children with relapsed/refractory acute lymphoblastic leukemia (ALL) either respond transiently or are initially resistant. Resistance to Moxe in cultured cells is due to low expression of diphthamide genes (DPH), but only two of six ALL blast samples from resistant patients had low DPH expression. To develop a more clinically relevant model of resistance, we treated NSG mice bearing KOPN-8 or Reh cells with Moxe. More than 99.9% of the cancer cells were killed by Moxe, but relapse occurred from discrete bone marrow sites. The resistant cells would no longer grow in cell culture and showed major chromosomal changes and changes in phenotype with greatly decreased CD22. RNA deep sequencing of resistant KOPN-8 blasts revealed global changes in gene expression, indicating dedifferentiation toward less-mature B cell precursors, and showed an up-regulation of myeloid genes. When Moxe was combined with 5-azacytidine, resistance was prevented and survival increased to over 5 months in the KOPN-8 model and greatly improved in the Reh model. We conclude that Moxe resistance in mice is due to a new mechanism that could not be observed using cultured cells and is prevented by treatment with 5-azacytidine.}, } @article {pmid29432153, year = {2018}, author = {}, title = {Correction for Sanderman et al., Soil carbon debt of 12,000 years of human land use.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1700}, doi = {10.1073/pnas.1800925115}, pmid = {29432153}, issn = {1091-6490}, } @article {pmid29432152, year = {2018}, author = {Ansari, S and Troelenberg, N and Dao, VA and Richter, T and Bucher, G and Klingler, M}, title = {Double abdomen in a short-germ insect: Zygotic control of axis formation revealed in the beetle Tribolium castaneum.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1819-1824}, pmid = {29432152}, issn = {1091-6490}, mesh = {Abdomen/embryology ; Animals ; Body Patterning ; Drosophila/embryology/genetics/metabolism ; Female ; Gene Expression Regulation, Developmental ; Germ Cells/metabolism ; Insect Proteins/genetics/metabolism ; Male ; Tribolium/*embryology/*genetics/metabolism ; Zygote/metabolism ; }, abstract = {The distinction of anterior versus posterior is a crucial first step in animal embryogenesis. In the fly Drosophila, this axis is established by morphogenetic gradients contributed by the mother that regulate zygotic target genes. This principle has been considered to hold true for insects in general but is fundamentally different from vertebrates, where zygotic genes and Wnt signaling are required. We investigated symmetry breaking in the beetle Tribolium castaneum, which among insects represents the more ancestral short-germ embryogenesis. We found that maternal Tc-germ cell-less is required for anterior localization of maternal Tc-axin, which represses Wnt signaling and promotes expression of anterior zygotic genes. Both RNAi targeting Tc-germ cell-less or double RNAi knocking down the zygotic genes Tc-homeobrain and Tc-zen1 led to the formation of a second growth zone at the anterior, which resulted in double-abdomen phenotypes. Conversely, interfering with two posterior factors, Tc-caudal and Wnt, caused double-anterior phenotypes. These findings reveal that maternal and zygotic mechanisms, including Wnt signaling, are required for establishing embryo polarity and induce the segmentation clock in a short-germ insect.}, } @article {pmid29432151, year = {2018}, author = {Ahmed, IAM and Maher, BA}, title = {Identification and paleoclimatic significance of magnetite nanoparticles in soils.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1736-1741}, pmid = {29432151}, issn = {1091-6490}, abstract = {In the world-famous sediments of the Chinese Loess Plateau, fossil soils alternate with windblown dust layers to record monsoonal variations over the last ∼3 My. The less-weathered, weakly magnetic dust layers reflect drier, colder glaciations. The fossil soils (paleosols) contain variable concentrations of nanoscale, strongly magnetic iron oxides, formed in situ during the wetter, warmer interglaciations. Mineralogical identification of the magnetic soil oxides is essential for deciphering these key paleoclimatic records. Formation of magnetite, a mixed Fe2+/Fe3+ ferrimagnet, has been linked to soil redox oscillations, and thence to paleorainfall. An opposite hypothesis states that magnetite can only form if the soil is water saturated for significant periods in order for Fe3+ to be reduced to Fe2+, and suggests instead the temperature-dependent formation of maghemite, an Fe3+-oxide, much of which ages subsequently into hematite, typically aluminum substituted. This latter, oxidizing pathway would have been temperature, but not rainfall dependent. Here, through structural fingerprinting and scanning transmission electron microscopy and electron energy loss spectroscopy analysis, we prove that magnetite is the dominant soil-formed ferrite. Maghemite is present in lower concentrations, and shows no evidence of aluminum substitution, negating its proposed precursor role for the aluminum-substituted hematite prevalent in the paleosols. Magnetite dominance demonstrates that magnetite formation occurs in well-drained, generally oxidizing soils, and that soil wetting/drying oscillations drive the degree of soil magnetic enhancement. The magnetic variations of the Chinese Loess Plateau paleosols thus record changes in monsoonal rainfall, over timescales of millions of years.}, } @article {pmid29432150, year = {2018}, author = {Gabrielsen, P}, title = {QnAs with Martin Head-Gordon.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1670-1671}, pmid = {29432150}, issn = {1091-6490}, } @article {pmid29432149, year = {2018}, author = {Zahran, S and McElmurry, SP and Kilgore, PE and Mushinski, D and Press, J and Love, NG and Sadler, RC and Swanson, MS}, title = {Assessment of the Legionnaires' disease outbreak in Flint, Michigan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1730-E1739}, pmid = {29432149}, issn = {1091-6490}, support = {R21 ES027199/ES/NIEHS NIH HHS/United States ; }, mesh = {Chlorine ; *Disease Outbreaks ; Drinking Water/chemistry/*microbiology ; Humans ; Legionella pneumophila/*isolation & purification ; Legionnaires' Disease/*epidemiology ; Michigan/epidemiology ; Risk Factors ; *Water Microbiology ; *Water Supply ; }, abstract = {The 2014-2015 Legionnaires' disease (LD) outbreak in Genesee County, MI, and the outbreak resolution in 2016 coincided with changes in the source of drinking water to Flint's municipal water system. Following the switch in water supply from Detroit to Flint River water, the odds of a Flint resident presenting with LD increased 6.3-fold (95% CI: 2.5, 14.0). This risk subsided following boil water advisories, likely due to residents avoiding water, and returned to historically normal levels with the switch back in water supply. During the crisis, as the concentration of free chlorine in water delivered to Flint residents decreased, their risk of acquiring LD increased. When the average weekly chlorine level in a census tract was <0.5 mg/L or <0.2 mg/L, the odds of an LD case presenting from a Flint neighborhood increased by a factor of 2.9 (95% CI: 1.4, 6.3) or 3.9 (95% CI: 1.8, 8.7), respectively. During the switch, the risk of a Flint neighborhood having a case of LD increased by 80% per 1 mg/L decrease in free chlorine, as calculated from the extensive variation in chlorine observed. In communities adjacent to Flint, the probability of LD occurring increased with the flow of commuters into Flint. Together, the results support the hypothesis that a system-wide proliferation of legionellae was responsible for the LD outbreak in Genesee County, MI.}, } @article {pmid29432148, year = {2018}, author = {Chhabra, S and Fischer, P and Takeuchi, K and Dubey, A and Ziarek, JJ and Boeszoermenyi, A and Mathieu, D and Bermel, W and Davey, NE and Wagner, G and Arthanari, H}, title = {15N detection harnesses the slow relaxation property of nitrogen: Delivering enhanced resolution for intrinsically disordered proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1710-E1719}, pmid = {29432148}, issn = {1091-6490}, support = {K99 GM115814/GM/NIGMS NIH HHS/United States ; P01 GM047467/GM/NIGMS NIH HHS/United States ; P41 EB002026/EB/NIBIB NIH HHS/United States ; }, mesh = {*Magnetic Resonance Spectroscopy ; NFATC Transcription Factors/*chemistry ; Nitrogen Isotopes/*chemistry ; Protein Conformation ; }, abstract = {Studies over the past decade have highlighted the functional significance of intrinsically disordered proteins (IDPs). Due to conformational heterogeneity and inherent dynamics, structural studies of IDPs have relied mostly on NMR spectroscopy, despite IDPs having characteristics that make them challenging to study using traditional 1H-detected biomolecular NMR techniques. Here, we develop a suite of 3D 15N-detected experiments that take advantage of the slower transverse relaxation property of 15N nuclei, the associated narrower linewidth, and the greater chemical shift dispersion compared with those of 1H and 13C resonances. The six 3D experiments described here start with aliphatic 1H magnetization to take advantage of its higher initial polarization, and are broadly applicable for backbone assignment of proteins that are disordered, dynamic, or have unfavorable amide proton exchange rates. Using these experiments, backbone resonance assignments were completed for the unstructured regulatory domain (residues 131-294) of the human transcription factor nuclear factor of activated T cells (NFATC2), which includes 28 proline residues located in functionally important serine-proline (SP) repeats. The complete assignment of the NFATC2 regulatory domain enabled us to study phosphorylation of NFAT by kinase PKA and phosphorylation-dependent binding of chaperone protein 14-3-3 to NFAT, providing mechanistic insight on how 14-3-3 regulates NFAT nuclear translocation.}, } @article {pmid29432147, year = {2018}, author = {Seebens, H and Blackburn, TM and Dyer, EE and Genovesi, P and Hulme, PE and Jeschke, JM and Pagad, S and Pyšek, P and van Kleunen, M and Winter, M and Ansong, M and Arianoutsou, M and Bacher, S and Blasius, B and Brockerhoff, EG and Brundu, G and Capinha, C and Causton, CE and Celesti-Grapow, L and Dawson, W and Dullinger, S and Economo, EP and Fuentes, N and Guénard, B and Jäger, H and Kartesz, J and Kenis, M and Kühn, I and Lenzner, B and Liebhold, AM and Mosena, A and Moser, D and Nentwig, W and Nishino, M and Pearman, D and Pergl, J and Rabitsch, W and Rojas-Sandoval, J and Roques, A and Rorke, S and Rossinelli, S and Roy, HE and Scalera, R and Schindler, S and Štajerová, K and Tokarska-Guzik, B and Walker, K and Ward, DF and Yamanaka, T and Essl, F}, title = {Global rise in emerging alien species results from increased accessibility of new source pools.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {E2264-E2273}, pmid = {29432147}, issn = {1091-6490}, mesh = {Animals ; Biodiversity ; Ecosystem ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, 21st Century ; Introduced Species/history/*statistics & numerical data ; Models, Biological ; Population Dynamics/history ; }, abstract = {Our ability to predict the identity of future invasive alien species is largely based upon knowledge of prior invasion history. Emerging alien species-those never encountered as aliens before-therefore pose a significant challenge to biosecurity interventions worldwide. Understanding their temporal trends, origins, and the drivers of their spread is pivotal to improving prevention and risk assessment tools. Here, we use a database of 45,984 first records of 16,019 established alien species to investigate the temporal dynamics of occurrences of emerging alien species worldwide. Even after many centuries of invasions the rate of emergence of new alien species is still high: One-quarter of first records during 2000-2005 were of species that had not been previously recorded anywhere as alien, though with large variation across taxa. Model results show that the high proportion of emerging alien species cannot be solely explained by increases in well-known drivers such as the amount of imported commodities from historically important source regions. Instead, these dynamics reflect the incorporation of new regions into the pool of potential alien species, likely as a consequence of expanding trade networks and environmental change. This process compensates for the depletion of the historically important source species pool through successive invasions. We estimate that 1-16% of all species on Earth, depending on the taxonomic group, qualify as potential alien species. These results suggest that there remains a high proportion of emerging alien species we have yet to encounter, with future impacts that are difficult to predict.}, } @article {pmid29432146, year = {2018}, author = {Simonet, P and Gaget, K and Balmand, S and Ribeiro Lopes, M and Parisot, N and Buhler, K and Duport, G and Vulsteke, V and Febvay, G and Heddi, A and Charles, H and Callaerts, P and Calevro, F}, title = {Bacteriocyte cell death in the pea aphid/Buchnera symbiotic system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1819-E1828}, pmid = {29432146}, issn = {1091-6490}, mesh = {Animals ; Aphids/*microbiology ; Buchnera/*physiology ; Cell Death ; Lysosomes ; Symbiosis/*physiology ; }, abstract = {Symbiotic associations play a pivotal role in multicellular life by facilitating acquisition of new traits and expanding the ecological capabilities of organisms. In insects that are obligatorily dependent on intracellular bacterial symbionts, novel host cells (bacteriocytes) or organs (bacteriomes) have evolved for harboring beneficial microbial partners. The processes regulating the cellular life cycle of these endosymbiont-bearing cells, such as the cell-death mechanisms controlling their fate and elimination in response to host physiology, are fundamental questions in the biology of symbiosis. Here we report the discovery of a cell-death process involved in the degeneration of bacteriocytes in the hemipteran insect Acyrthosiphon pisum This process is activated progressively throughout aphid adulthood and exhibits morphological features distinct from known cell-death pathways. By combining electron microscopy, immunohistochemistry, and molecular analyses, we demonstrated that the initial event of bacteriocyte cell death is the cytoplasmic accumulation of nonautophagic vacuoles, followed by a sequence of cellular stress responses including the formation of autophagosomes in intervacuolar spaces, activation of reactive oxygen species, and Buchnera endosymbiont degradation by the lysosomal system. We showed that this multistep cell-death process originates from the endoplasmic reticulum, an organelle exhibiting a unique reticular network organization spread throughout the entire cytoplasm and surrounding Buchnera aphidicola endosymbionts. Our findings provide insights into the cellular and molecular processes that coordinate eukaryotic host and endosymbiont homeostasis and death in a symbiotic system and shed light on previously unknown aspects of bacteriocyte biological functioning.}, } @article {pmid29432145, year = {2018}, author = {Li, B and Ji, C and Yang, W and Wang, J and Yang, K and Xu, R and Liu, W and Cai, Z and Chen, J and Mao, HK}, title = {Diamond anvil cell behavior up to 4 Mbar.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1713-1717}, pmid = {29432145}, issn = {1091-6490}, abstract = {The diamond anvil cell (DAC) is considered one of the dominant devices to generate ultrahigh static pressure. The development of the DAC technique has enabled researchers to explore rich high-pressure science in the multimegabar pressure range. Here, we investigated the behavior of the DAC up to 400 GPa, which is the accepted pressure limit of a conventional DAC. By using a submicrometer synchrotron X-ray beam, double cuppings of the beveled diamond anvils were observed experimentally. Details of pressure loading, distribution, gasket-thickness variation, and diamond anvil deformation were studied to understand the generation of ultrahigh pressures, which may improve the conventional DAC techniques.}, } @article {pmid29432144, year = {2018}, author = {Hartel, AJW and Ong, P and Schroeder, I and Giese, MH and Shekar, S and Clarke, OB and Zalk, R and Marks, AR and Hendrickson, WA and Shepard, KL}, title = {Single-channel recordings of RyR1 at microsecond resolution in CMOS-suspended membranes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1789-E1798}, pmid = {29432144}, issn = {1091-6490}, support = {R01 HL061503/HL/NHLBI NIH HHS/United States ; T32 HL120826/HL/NHLBI NIH HHS/United States ; P41 GM116799/GM/NIGMS NIH HHS/United States ; R01 AR060037/AR/NIAMS NIH HHS/United States ; R01 HG009189/HG/NHGRI NIH HHS/United States ; R01 HG006879/HG/NHGRI NIH HHS/United States ; }, mesh = {Calcium Signaling ; Cell Membrane ; Electrochemical Techniques ; Ion Channel Gating ; Lipid Bilayers/*chemistry ; Metals/chemistry ; Oxides/chemistry ; Ryanodine Receptor Calcium Release Channel/*chemistry/metabolism ; *Semiconductors ; Time Factors ; }, abstract = {Single-channel recordings are widely used to explore functional properties of ion channels. Typically, such recordings are performed at bandwidths of less than 10 kHz because of signal-to-noise considerations, limiting the temporal resolution available for studying fast gating dynamics to greater than 100 µs. Here we present experimental methods that directly integrate suspended lipid bilayers with high-bandwidth, low-noise transimpedance amplifiers based on complementary metal-oxide-semiconductor (CMOS) integrated circuits (IC) technology to achieve bandwidths in excess of 500 kHz and microsecond temporal resolution. We use this CMOS-integrated bilayer system to study the type 1 ryanodine receptor (RyR1), a Ca2+-activated intracellular Ca2+-release channel located on the sarcoplasmic reticulum. We are able to distinguish multiple closed states not evident with lower bandwidth recordings, suggesting the presence of an additional Ca2+ binding site, distinct from the site responsible for activation. An extended beta distribution analysis of our high-bandwidth data can be used to infer closed state flicker events as fast as 35 ns. These events are in the range of single-file ion translocations.}, } @article {pmid29430636, year = {2018}, author = {Brengdahl, M and Kimber, CM and Maguire-Baxter, J and Friberg, U}, title = {Sex differences in life span: Females homozygous for the X chromosome do not suffer the shorter life span predicted by the unguarded X hypothesis.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {568-577}, doi = {10.1111/evo.13434}, pmid = {29430636}, issn = {1558-5646}, abstract = {Life span differs between the sexes in many species. Three hypotheses to explain this interesting pattern have been proposed, involving different drivers: sexual selection, asymmetrical inheritance of cytoplasmic genomes, and hemizygosity of the X(Z) chromosome (the unguarded X hypothesis). Of these, the unguarded X has received the least experimental attention. This hypothesis suggests that the heterogametic sex suffers a shortened life span because recessive deleterious alleles on its single X(Z) chromosome are expressed unconditionally. In Drosophila melanogaster, the X chromosome is unusually large (∼20% of the genome), providing a powerful model for evaluating theories involving the X. Here, we test the unguarded X hypothesis by forcing D. melanogaster females from a laboratory population to express recessive X-linked alleles to the same degree as males, using females exclusively made homozygous for the X chromosome. We find no evidence for reduced life span or egg-to-adult viability due to X homozygozity. In contrast, males and females homozygous for an autosome both suffer similar, significant reductions in those traits. The logic of the unguarded X hypothesis is indisputable, but our results suggest that the degree to which recessive deleterious X-linked alleles depress performance in the heterogametic sex appears too small to explain general sex differences in life span.}, } @article {pmid29430012, year = {2018}, author = {Langmead, B and Nellore, A}, title = {Cloud computing for genomic data analysis and collaboration.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {325}, pmid = {29430012}, issn = {1471-0064}, support = {R01 GM118568/GM/NIGMS NIH HHS/United States ; }, abstract = {This corrects the article DOI: 10.1038/nrg.2017.113.}, } @article {pmid29430011, year = {2018}, author = {Quillin, SJ and Seifert, HS}, title = {Neisseria gonorrhoeae host adaptation and pathogenesis.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {226-240}, pmid = {29430011}, issn = {1740-1534}, support = {R37 AI033493/AI/NIAID NIH HHS/United States ; T32 AI007476/AI/NIAID NIH HHS/United States ; }, abstract = {The host-adapted human pathogen Neisseria gonorrhoeae is the causative agent of gonorrhoea. Consistent with its proposed evolution from an ancestral commensal bacterium, N. gonorrhoeae has retained features that are common in commensals, but it has also developed unique features that are crucial to its pathogenesis. The continued worldwide incidence of gonorrhoeal infection, coupled with the rising resistance to antimicrobials and the difficulties in controlling the disease in developing countries, highlights the need to better understand the molecular basis of N. gonorrhoeae infection. This knowledge will facilitate disease prevention, surveillance and control, improve diagnostics and may help to facilitate the development of effective vaccines or new therapeutics. In this Review, we discuss sex-related symptomatic gonorrhoeal disease and provide an overview of the bacterial factors that are important for the different stages of pathogenesis, including transmission, colonization and immune evasion, and we discuss the problem of antibiotic resistance.}, } @article {pmid29430007, year = {2018}, author = {York, A}, title = {Viral infection: Breathing alone may spread the flu.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {123}, pmid = {29430007}, issn = {1740-1534}, } @article {pmid29430006, year = {2018}, author = {York, A}, title = {Biofilms: Naturally modified cellulose in bacterial biofilms.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {123}, pmid = {29430006}, issn = {1740-1534}, } @article {pmid29430005, year = {2018}, author = {Neufeldt, CJ and Cortese, M and Acosta, EG and Bartenschlager, R}, title = {Rewiring cellular networks by members of the Flaviviridae family.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {125-142}, pmid = {29430005}, issn = {1740-1534}, abstract = {Members of the Flaviviridae virus family comprise a large group of enveloped viruses with a single-strand RNA genome of positive polarity. Several genera belong to this family, including the Hepacivirus genus, of which hepatitis C virus (HCV) is the prototype member, and the Flavivirus genus, which contains both dengue virus and Zika virus. Viruses of these genera differ in many respects, such as the mode of transmission or the course of infection, which is either predominantly persistent in the case of HCV or acutely self-limiting in the case of flaviviruses. Although the fundamental replication strategy of Flaviviridae members is similar, during the past few years, important differences have been discovered, including the way in which these viruses exploit cellular resources to facilitate viral propagation. These differences might be responsible, at least in part, for the various biological properties of these viruses, thus offering the possibility to learn from comparisons. In this Review, we discuss the current understanding of how Flaviviridae viruses manipulate and usurp cellular pathways in infected cells. Specifically, we focus on comparing strategies employed by flaviviruses with those employed by hepaciviruses, and we discuss the importance of these interactions in the context of viral replication and antiviral therapies.}, } @article {pmid29430004, year = {2018}, author = {Du Toit, A}, title = {Antimicrobials: Bacterial enzymes 'straighten out' antibiotics.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {122}, pmid = {29430004}, issn = {1740-1534}, } @article {pmid29430003, year = {2018}, author = {Du Toit, A}, title = {Bacterial physiology: Spacers go off-site.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {122}, pmid = {29430003}, issn = {1740-1534}, } @article {pmid29430002, year = {2018}, author = {York, A}, title = {Marine microbiology: A new tale for oceanic viruses.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {123}, pmid = {29430002}, issn = {1740-1534}, } @article {pmid29430001, year = {2018}, author = {Du Toit, A}, title = {Environmental microbiology: Attracting bacteria in the soil.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {122}, pmid = {29430001}, issn = {1740-1534}, } @article {pmid29429965, year = {2018}, author = {Saadalla, AM and Osman, A and Gurish, MF and Dennis, KL and Blatner, NR and Pezeshki, A and McNagny, KM and Cheroutre, H and Gounari, F and Khazaie, K}, title = {Mast cells promote small bowel cancer in a tumor stage-specific and cytokine-dependent manner.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1588-1592}, pmid = {29429965}, issn = {1091-6490}, support = {R01 AI108682/AI/NIAID NIH HHS/United States ; R01 CA160436/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cells, Cultured ; Chymases/*metabolism ; Cytokines/*metabolism ; Intestinal Neoplasms/immunology/metabolism/*pathology ; Intestine, Small/immunology/metabolism/*pathology ; Lymphocytes/immunology/metabolism/*pathology ; Mast Cells/immunology/metabolism/*pathology ; Mice ; Mucous Membrane/immunology/metabolism/*pathology ; Neoplasm Staging ; }, abstract = {Mast cells (MCs) are tissue resident sentinels that mature and orchestrate inflammation in response to infection and allergy. While they are also frequently observed in tumors, the contribution of MCs to carcinogenesis remains unclear. Here, we show that sequential oncogenic events in gut epithelia expand different types of MCs in a temporal-, spatial-, and cytokine-dependent manner. The first wave of MCs expands focally in benign adenomatous polyps, which have elevated levels of IL-10, IL-13, and IL-33, and are rich in type-2 innate lymphoid cells (ILC2s). These vanguard MCs adhere to the transformed epithelial cells and express murine mast cell protease 2 (mMCP2; a typical mucosal MC protease) and, to a lesser extent, the connective tissue mast cell (CTMC) protease mMCP6. Persistence of MCs is strictly dependent on T cell-derived IL-10, and their loss in the absence of IL-10-expressing T cells markedly delays small bowel (SB) polyposis. MCs expand profusely in polyposis-prone mice when T cells overexpress IL-10. The frequency of polyp-associated MCs is unaltered in response to broad-spectrum antibiotics, arguing against a microbial component driving their recruitment. Intriguingly, when polyps become invasive, a second wave of mMCP5+/mMCP6+ CTMCs expands in the tumor stroma and at invasive tumor borders. Ablation of mMCP6 expression attenuates polyposis, but invasive properties of the remaining lesions remain intact. Our findings argue for a multistep process in SB carcinogenesis in which distinct MC subsets, and their elaborated proteases, guide disease progression.}, } @article {pmid29429964, year = {2018}, author = {Adler, M and Mayo, A and Zhou, X and Franklin, RA and Jacox, JB and Medzhitov, R and Alon, U}, title = {Endocytosis as a stabilizing mechanism for tissue homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {E1926-E1935}, pmid = {29429964}, issn = {1091-6490}, support = {T32 GM007205/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Cell Physiological Phenomena ; Cells/chemistry ; *Endocytosis ; Homeostasis ; Models, Biological ; Models, Theoretical ; }, abstract = {Cells in tissues communicate by secreted growth factors (GF) and other signals. An important function of cell circuits is tissue homeostasis: maintaining proper balance between the amounts of different cell types. Homeostasis requires negative feedback on the GFs, to avoid a runaway situation in which cells stimulate each other and grow without control. Feedback can be obtained in at least two ways: endocytosis in which a cell removes its cognate GF by internalization and cross-inhibition in which a GF down-regulates the production of another GF. Here we ask whether there are design principles for cell circuits to achieve tissue homeostasis. We develop an analytically solvable framework for circuits with multiple cell types and find that feedback by endocytosis is far more robust to parameter variation and has faster responses than cross-inhibition. Endocytosis, which is found ubiquitously across tissues, can even provide homeostasis to three and four communicating cell types. These design principles form a conceptual basis for how tissues maintain a healthy balance of cell types and how balance may be disrupted in diseases such as degeneration and fibrosis.}, } @article {pmid29429765, year = {2018}, author = {Schofield, EJ and Rowntree, JK and Paterson, E and Brooker, RW}, title = {Temporal Dynamism of Resource Capture: A Missing Factor in Ecology?.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {277-286}, doi = {10.1016/j.tree.2018.01.009}, pmid = {29429765}, issn = {1872-8383}, mesh = {Botany/*instrumentation ; *Plant Physiological Phenomena ; Plants/*metabolism ; Seasons ; }, abstract = {Temporal dynamism of plant resource capture, and its impacts on plant-plant interactions, can have important regulatory roles in multispecies communities. For example, by modifying resource acquisition timing, plants might reduce competition and promote their coexistence. However, despite the potential wide ecological relevance of this topic, short-term (within growing season) temporal dynamism has been overlooked. This is partially a consequence of historic reliance on measures made at single points in time. We propose that with current technological advances this is a golden opportunity to study within growing season temporal dynamism of resource capture by plants in highly informative ways. We set out here an agenda for future developments in this research field, and explore how new technologies can deliver this agenda.}, } @article {pmid29429760, year = {2018}, author = {Carney, TJ and Mosimann, C}, title = {Switch and Trace: Recombinase Genetics in Zebrafish.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {362-378}, doi = {10.1016/j.tig.2018.01.004}, pmid = {29429760}, issn = {0168-9525}, mesh = {Animals ; Animals, Genetically Modified ; *Gene Transfer Techniques ; Genome/genetics ; Mutagenesis, Insertional/genetics ; Recombinases/*genetics ; *Recombination, Genetic ; Transgenes/genetics ; Zebrafish/*genetics/growth & development ; }, abstract = {Transgenic approaches are instrumental for labeling and manipulating cells and cellular machineries in vivo. Transgenes have traditionally been static entities that remained unaltered following genome integration, limiting their versatility. The development of DNA recombinase-based methods to modify, excise, or rearrange transgene cassettes has introduced versatile control of transgene activity and function. In particular, recombinase-controlled transgenes enable regulation of exogenous gene expression, conditional mutagenesis, and genetic lineage tracing. In zebrafish, transgenesis-based recombinase genetics using Cre/lox, Flp/FRT, and ΦC31 are increasingly applied to study development and homeostasis, and to generate disease models. Intersected with the versatile imaging capacity of the zebrafish model and recent breakthroughs in genome editing, we review and discuss past, current, and potential future approaches and resources for recombinase-based techniques in zebrafish.}, } @article {pmid29429061, year = {2018}, author = {Loeza-Quintana, T and Adamowicz, SJ}, title = {Iterative Calibration: A Novel Approach for Calibrating the Molecular Clock Using Complex Geological Events.}, journal = {Journal of molecular evolution}, volume = {86}, number = {2}, pages = {118-137}, pmid = {29429061}, issn = {1432-1432}, support = {315757//Consejo Nacional de Ciencia y Tecnología/ ; 2010-386591//Natural Sciences and Engineering Research Council of Canada/ ; 2016-06199//Natural Sciences and Engineering Research Council of Canada/ ; }, abstract = {During the past 50 years, the molecular clock has become one of the main tools for providing a time scale for the history of life. In the era of robust molecular evolutionary analysis, clock calibration is still one of the most basic steps needing attention. When fossil records are limited, well-dated geological events are the main resource for calibration. However, biogeographic calibrations have often been used in a simplistic manner, for example assuming simultaneous vicariant divergence of multiple sister lineages. Here, we propose a novel iterative calibration approach to define the most appropriate calibration date by seeking congruence between the dates assigned to multiple allopatric divergences and the geological history. Exploring patterns of molecular divergence in 16 trans-Bering sister clades of echinoderms, we demonstrate that the iterative calibration is predominantly advantageous when using complex geological or climatological events-such as the opening/reclosure of the Bering Strait-providing a powerful tool for clock dating that can be applied to other biogeographic calibration systems and further taxa. Using Bayesian analysis, we observed that evolutionary rate variability in the COI-5P gene is generally distributed in a clock-like fashion for Northern echinoderms. The results reveal a large range of genetic divergences, consistent with multiple pulses of trans-Bering migrations. A resulting rate of 2.8% pairwise Kimura-2-parameter sequence divergence per million years is suggested for the COI-5P gene in Northern echinoderms. Given that molecular rates may vary across latitudes and taxa, this study provides a new context for dating the evolutionary history of Arctic marine life.}, } @article {pmid29428562, year = {2018}, author = {Gerhardt, B and Leesman, L and Burra, K and Snowball, J and Rosenzweig, R and Guzman, N and Ambalavanan, M and Sinner, D}, title = {Notum attenuates Wnt/β-catenin signaling to promote tracheal cartilage patterning.}, journal = {Developmental biology}, volume = {436}, number = {1}, pages = {14-27}, pmid = {29428562}, issn = {1095-564X}, support = {K01 HL115447/HL/NHLBI NIH HHS/United States ; R03 HL133420/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Body Patterning/genetics ; Cartilage/embryology/*metabolism ; Cell Culture Techniques ; Cell Migration Assays ; Cell Proliferation ; Chondrogenesis/genetics ; Esterases/*metabolism ; Gene Expression Profiling ; Gene Expression Regulation, Developmental ; Genotyping Techniques ; In Situ Hybridization ; Mice ; Real-Time Polymerase Chain Reaction ; Trachea/embryology/*metabolism ; Transfection ; Wnt Signaling Pathway/*genetics ; beta Catenin/*metabolism ; }, abstract = {Tracheobronchomalacia (TBM) is a common congenital disorder in which the cartilaginous rings of the trachea are weakened or missing. Despite the high prevalence and clinical issues associated with TBM, the etiology is largely unknown. Our previous studies demonstrated that Wntless (Wls) and its associated Wnt pathways are critical for patterning of the upper airways. Deletion of Wls in respiratory endoderm caused TBM and ectopic trachealis muscle. To understand mechanisms by which Wls mediates tracheal patterning, we performed RNA sequencing in prechondrogenic tracheal tissue of Wlsf/f;ShhCre/wt embryos. Chondrogenic Bmp4, and Sox9 were decreased, while expression of myogenic genes was increased. We identified Notum, a deacylase that inactivates Wnt ligands, as a target of Wls induced Wnt signaling. Notum's mesenchymal ventral expression in prechondrogenic trachea overlaps with expression of Axin2, a Wnt/β-catenin target and inhibitor. Notum is induced by Wnt/β-catenin in developing trachea. Deletion of Notum activated mesenchymal Wnt/β-catenin and caused tracheal mispatterning of trachealis muscle and cartilage as well as tracheal stenosis. Notum is required for tracheal morphogenesis, influencing mesenchymal condensations critical for patterning of tracheal cartilage and muscle. We propose that Notum influences mesenchymal cell differentiation by generating a barrier for Wnt ligands produced and secreted by airway epithelial cells to attenuate Wnt signaling.}, } @article {pmid29428510, year = {2018}, author = {Wilson, JD and Hughes, JM and Raven, RJ and Rix, MG and Schmidt, DJ}, title = {Spiny trapdoor spiders (Euoplos) of eastern Australia: Broadly sympatric clades are differentiated by burrow architecture and male morphology.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {157-165}, doi = {10.1016/j.ympev.2018.01.022}, pmid = {29428510}, issn = {1095-9513}, mesh = {Animals ; Australia ; Biological Evolution ; Electron Transport Complex IV/genetics ; Female ; Male ; *Phylogeny ; Sequence Analysis, DNA ; Spiders/*anatomy & histology/*classification/genetics ; Sympatry ; }, abstract = {Spiders of the infraorder Mygalomorphae are fast becoming model organisms for the study of biogeography and speciation. However, these spiders can be difficult to study in the absence of fundamental life history information. In particular, their cryptic nature hinders comprehensive sampling, and linking males with conspecific females can be challenging. Recently discovered differences in burrow entrance architecture and male morphology indicated that these challenges may have impeded our understanding of the trapdoor spider genus Euoplos in Australia's eastern mesic zone. We investigated the evolutionary significance of these discoveries using a multi-locus phylogenetic approach. Our results revealed the existence of a second, previously undocumented, lineage of Euoplos in the eastern mesic zone. This new lineage occurs in sympatry with a lineage previously known from the region, and the two are consistently divergent in their burrow entrance architecture and male morphology, revealing the suitability of these characters for use in phylogenetic studies. Divergent burrow entrance architecture and observed differences in microhabitat preferences are suggested to facilitate sympatry and syntopy between the lineages. Finally, by investigating male morphology and plotting it onto the phylogeny, we revealed that the majority of Euoplos species remain undescribed, and that males of an unnamed species from the newly discovered lineage had historically been linked, erroneously, to a described species from the opposite lineage. This paper clarifies the evolutionary relationships underlying life history diversity in the Euoplos of eastern Australia, and provides a foundation for urgently needed taxonomic revision of this genus.}, } @article {pmid29428509, year = {2018}, author = {Sahoo, RK and Lohman, DJ and Wahlberg, N and Müller, CJ and Brattström, O and Collins, SC and Peggie, D and Aduse-Poku, K and Kodandaramaiah, U}, title = {Evolution of Hypolimnas butterflies (Nymphalidae): Out-of-Africa origin and Wolbachia-mediated introgression.}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {50-58}, doi = {10.1016/j.ympev.2018.02.001}, pmid = {29428509}, issn = {1095-9513}, mesh = {Africa ; Animals ; Base Sequence ; Bayes Theorem ; Biodiversity ; *Biological Evolution ; Butterflies/*genetics/*microbiology ; DNA, Mitochondrial/genetics ; Haplotypes/genetics ; Larva/physiology ; Likelihood Functions ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Wolbachia/*physiology ; }, abstract = {Hypolimnas butterflies (Nymphalidae), commonly known as eggflies, are a popular model system for studying a wide range of ecological questions including mimicry, polymorphism, wing pattern evolution, and Wolbachia-host interactions. The lack of a time-calibrated phylogeny for this group has precluded understanding its evolutionary history. We reconstruct a species-level phylogeny using a nine gene dataset and estimate species divergence times. Based on the resulting tree, we investigate the taxon's historical biogeography, examine the evolution of host plant preferences, and test the hypothesis that the endosymbiotic bacterium Wolbachia mediates gene transfer between species. Our analyses indicate that the species are grouped within three strongly supported, deeply divergent clades. However, relationships among these three clades are uncertain. In addition, many Hypolimnas species are not monophyletic or monophyletic with weak support, suggesting widespread incomplete lineage sorting and/or introgression. Biogeographic analysis strongly indicates that the genus diverged from its ancestor in Africa and subsequently dispersed to Asia; the strength of this result is not affected by topological uncertainties. While the larvae of African species feed almost exclusively on Urticaceae, larvae of species found further east often feed on several additional families. Interestingly, we found an identical mitochondrial haplotype in two Hypolimnas species, H. bolina and H. alimena, and a strong association between this mitotype and the Wolbachia strain wBol1a. Future investigations should explore the plausibility of Wolbachia-mediated introgression between species.}, } @article {pmid29428235, year = {2018}, author = {Travers, T and Wang, KJ and López, CA and Gnanakaran, S}, title = {Sequence- and structure-based computational analyses of Gram-negative tripartite efflux pumps in the context of bacterial membranes.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {414-424}, doi = {10.1016/j.resmic.2018.01.002}, pmid = {29428235}, issn = {1769-7123}, mesh = {Bacterial Proteins/*chemistry/genetics/metabolism ; Cell Membrane/*chemistry/genetics/metabolism ; Computational Biology ; Gram-Negative Bacteria/chemistry/genetics/*metabolism ; Gram-Negative Bacterial Infections/microbiology ; Humans ; Membrane Transport Proteins/*chemistry/genetics/metabolism ; Models, Molecular ; }, abstract = {Gram-negative multidrug resistance currently presents a serious threat to public health with infections effectively rendered untreatable. Multiple molecular mechanisms exist that cause antibiotic resistance and in addition, the last three decades have seen slowing rates of new drug development. In this review, we summarize the use of various computational techniques for investigating the mechanisms of multidrug resistance mediated by Gram-negative tripartite efflux pumps and membranes. Recent work in our lab combines data-driven sequence and structure analyses to study the interactions and dynamics of these bacterial components. Computational studies can complement experimental methodologies for gaining crucial insights into combatting multidrug resistance.}, } @article {pmid29427778, year = {2019}, author = {De Silva, TN and Bates, JM and Peterson, AT}, title = {Getting the Ploceidae tree right.}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {228}, doi = {10.1016/j.ympev.2018.02.004}, pmid = {29427778}, issn = {1095-9513}, } @article {pmid29427777, year = {2019}, author = {Prager, M}, title = {Unweaving a taxon tangle: Comments on De Silva et al. (2017).}, journal = {Molecular phylogenetics and evolution}, volume = {131}, number = {}, pages = {229-232}, doi = {10.1016/j.ympev.2018.02.005}, pmid = {29427777}, issn = {1095-9513}, } @article {pmid29427638, year = {2018}, author = {Li, Q and Li, Z and Li, X and Xia, L and Zhou, X and Xu, Z and Shao, J and Shen, Q and Zhang, R}, title = {FtsEX-CwlO regulates biofilm formation by a plant-beneficial rhizobacterium Bacillus velezensis SQR9.}, journal = {Research in microbiology}, volume = {169}, number = {3}, pages = {166-176}, doi = {10.1016/j.resmic.2018.01.004}, pmid = {29427638}, issn = {1769-7123}, mesh = {ATP-Binding Cassette Transporters/*genetics/metabolism ; Bacillus/*physiology ; Bacterial Proteins/genetics/metabolism ; Biofilms/*growth & development ; Gene Expression Regulation, Bacterial ; Metabolic Networks and Pathways ; Models, Biological ; Mutation ; N-Acetylmuramoyl-L-alanine Amidase/metabolism ; Phenotype ; Plant Roots/*microbiology ; Protein Binding ; *Rhizosphere ; }, abstract = {Bacillus velezensis strain SQR9 is a well-investigated rhizobacterium with an outstanding ability to colonize roots, enhance plant growth and suppress soil-borne diseases. The recognition that biofilm formation by plant-beneficial bacteria is crucial for their root colonization and function has resulted in increased interest in understanding molecular mechanisms related to biofilm formation. Here, we report that the gene ftsE, encoding the ATP-binding protein of an FtsEX ABC transporter, is required for efficient SQR9 biofilm formation. FtsEX has been reported to regulate the atolysin CwlO. We provided evidence that FtsEX-CwlO was involved in the regulation of SQR9 biofilm formation; however, this effect has little to do with CwlO autolysin activity. We propose that regulation of biofilm formation by CwlO was exerted through the spo0A pathway, since transcription of spo0A cascade genes was altered and their downstream extracellular matrix genes were downregulated in SQR9 ftsE/cwlO deletion mutants. CwlO was also shown to interact physically with KinB/KinD. CwlO may therefore interact with KinB/KinD to interfere with the spo0A pathway. This study revealed that FtsEX-CwlO plays a previously undiscovered regulatory role in biofilm formation by SQR9 that may enhance root colonization and plant-beneficial functions of SQR9 and other beneficial rhizobacteria as well.}, } @article {pmid29427007, year = {2018}, author = {Wang, JQ and Yu, M and Zhou, Y and Ye, BC}, title = {Proteomic Analysis of Normal Expression Differences Exist in Bacillus Subtilis 168 Cultivation.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {803-810}, pmid = {29427007}, issn = {1432-0991}, support = {31401592//National Natural Science Foundation of China/ ; 222201714051//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Bacillus subtilis/chemistry/*genetics/*growth & development/metabolism ; Bacterial Proteins/chemistry/*genetics/metabolism ; Gene Expression Regulation, Bacterial ; Histidine/metabolism ; *Proteomics ; Sulfur/metabolism ; Transcription, Genetic ; }, abstract = {Biological science discovery often involves comparing conditions to a normal state, but little is known about "normal." Therefore, we used proteomic strategy to compare data from replicate samples of Bacillus subtilis 168 which were grown under identical condition. The results show that 294 differentially expressed proteins were annotated in 88 Gene Ontology functional groups and enriched in 13 KEGG pathways. We assume that normal expression differences are associated with adaptation to diverse environments. Moreover, five proteins (CotY, ThiG, SspA, SspB, and SspE) and their related genes were identified as having significantly different expressions at translational and transcriptional levels. Most of them are related to stress resistance and germination, indicating that normal expression differences can be regarded as a rapid response mechanism for survival. However, unstable protein expression may cause some fermentative problems that were observed in histidine and sulfur metabolism pathways. Our study facilitates dissection of the influence of biological variance on cultivation safety and stability.}, } @article {pmid29427006, year = {2018}, author = {Alayande, AB and Aung, MM and Kim, IS}, title = {Correlation Between Quorum Sensing Signal Molecules and Pseudomonas aeruginosa's Biofilm Development and Virulency.}, journal = {Current microbiology}, volume = {75}, number = {7}, pages = {787-793}, pmid = {29427006}, issn = {1432-0991}, support = {18IFIP-B087389-05//Ministry of Land, Infrastructure, and Transport of Korean government./ ; }, mesh = {4-Butyrolactone/*analogs & derivatives/metabolism ; *Biofilms ; Humans ; Pseudomonas Infections/*microbiology ; Pseudomonas aeruginosa/genetics/growth & development/pathogenicity/*physiology ; Pyocyanine/metabolism ; *Quorum Sensing ; Virulence ; Virulence Factors/metabolism ; }, abstract = {Bacteria, when adhered to a substratum, can form biofilms. Nevertheless, many factors dictate biofilm formation and virulence factor production, including a response by the bacteria to their surroundings. This system is referred to as Quorum sensing (QS) also known as cell-cell communication. Pseudomonas aeruginosa is an infection causing agent in immune-compromised patients, it uses acyl-homoserine lactone (AHL) to coordinate its QS systems. In this work, the connection between some members of AHL produced by P. aeruginosa PAO1 and its biofilm development and the production of virulence factor was investigated. It was discovered that N-butanoyl-homoserine lactone (C4-HSL) and N-hexanoyl-L-homoserine lactone (C6-HSL) perform a more consequential and eminent function in the biofilm maturation and virulence factor production while N-(3-oxododecanoyl)-L-homoserine lactone (3OC12-HSL) plays a role in biofilm initiation. Because QS has been reported to be required for biofilm development and pathogenesis of P. aeruginosa, the results of this work have great importance and significance for the design of strategies for the control and prevention of biofilms.}, } @article {pmid29426895, year = {2018}, author = {Sipos, G and Prasanna, AN and Walter, MC and O'Connor, E and Bálint, B and Krizsán, K and Kiss, B and Hess, J and Varga, T and Slot, J and Riley, R and Bóka, B and Rigling, D and Barry, K and Lee, J and Mihaltcheva, S and LaButti, K and Lipzen, A and Waldron, R and Moloney, NM and Sperisen, C and Kredics, L and Vágvölgyi, C and Patrignani, A and Fitzpatrick, D and Nagy, I and Doyle, S and Anderson, JB and Grigoriev, IV and Güldener, U and Münsterkötter, M and Nagy, LG}, title = {Author Correction: Genome expansion and lineage-specific genetic innovations in the forest pathogenic fungi Armillaria.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {577}, doi = {10.1038/s41559-018-0469-7}, pmid = {29426895}, issn = {2397-334X}, abstract = {In the version of this Article originally published, it was incorrectly stated that "16,687 protein-coding genes were inferred for the most recent common ancestor (MRCA) of Armillaria"; the value was incorrect and it should have read "15,787". This has now been corrected.}, } @article {pmid29426372, year = {2018}, author = {Mnyambwa, NP and Lekule, I and Ngadaya, ES and Kimaro, G and Petrucka, P and Kim, DJ and Lymo, J and Kazwala, R and Mosha, F and Mfinanga, SG}, title = {Assessment of GeneXpert GxAlert platform for multi-drug resistant tuberculosis diagnosis and patients' linkage to care in Tanzania.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {121}, pmid = {29426372}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; *Antibiotics, Antitubercular ; *Drug Resistance, Multiple, Bacterial ; Humans ; Patient Acceptance of Health Care ; Patient Navigation ; *Rifampin ; Tanzania ; Tuberculosis, Multidrug-Resistant/*diagnosis/*therapy ; }, abstract = {OBJECTIVE: The gap between patients diagnosed with multi-drug resistant tuberculosis (MDR-TB) and enrolment in treatment is one of the major challenges in tuberculosis control programmes. A 4-year (2013-2016) retrospective review of patients' clinical data and subsequent in-depth interviews with health providers were conducted to assess the effectiveness of the GeneXpert GxAlert platform for MDR-TB diagnosis and its impact on linkage of patients to care in Tanzania.

RESULTS: A total of 782 new rifampicin resistant cases were notified, but only 242 (32.3%) were placed in an MDR-TB regimens. The remaining 540 (67.07%) patients were not on treatment, of which 103 patients had complete records on the GxAlert database. Of the 103 patients: 39 were judged as untraceable; 27 died before treatment; 12 were treated with first-line anti-TBs; 9 repeat tests did not show rifampicin resistance; 15 were not on treatment due to communication breakdown, and 1 patient was transferred outside the country. In-depth interviews with health providers suggested that the pre-treatment loss for the MDR-TB patients was primarily attributed to health system and patients themselves. We recommend strengthening the health system by developing and implementing well-defined interventions to ensure all diagnosed MDR-TB patients are accurately reported and timely linked to treatment.}, } @article {pmid29426371, year = {2018}, author = {Lee, STM and Keshavmurthy, S and Fontana, S and Takuma, M and Chou, WH and Chen, CA}, title = {Transcriptomic response in Acropora muricata under acute temperature stress follows preconditioned seasonal temperature fluctuations.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {119}, pmid = {29426371}, issn = {1756-0500}, support = {AS-100-TP2-A02-3//Academia Sinica/ ; 2012 2014//Academia Sinica/ ; }, mesh = {Animals ; Anthozoa/*metabolism ; Japan ; *Seasons ; Stress, Physiological/*physiology ; *Temperature ; *Transcriptome ; }, abstract = {OBJECTIVE: Global climate change has resulted in the decline of health and condition of various coral reefs worldwide. Here, we describe expression profiles of Acropora muricata collected during opposing seasons in Otsuki, Kochi, Japan to define the capacity of corals to cope with changing environmental conditions. Coral communities in Otsuki experience large temperature fluctuations between the winter (~ 16 °C) and summer (~ 27 °C).

RESULTS: Coral nubbins that were collected in the summer showed no change in photochemical efficiency when exposed to thermal or cold stress, while winter samples showed a decrease in photochemical health when subjected to thermal stress. Under cold stress, corals that were collected in the summer showed an up-regulation of actin-related protein and serine/threonine protein kinase, while corals collected during the winter did not show any cellular stress. On the other hand, under thermal stress, the most notable change was the up-regulation of phosphoenolpyruvate carboxykinase in corals that were collected during the winter season. Our observations in the differential genes expressed under temperature-derived stress suggest that A. muricata from Kochi may maintain physiological resilience due to the frequently encountered environmental stress, and this may play a role in the coral's thermal tolerance.}, } @article {pmid29426370, year = {2018}, author = {Fuge, TG and Bawore, SG and Solomon, DW and Hegana, TY}, title = {Patient delay in seeking tuberculosis diagnosis and associated factors in Hadiya Zone, Southern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {115}, pmid = {29426370}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; *Delayed Diagnosis ; Ethiopia/epidemiology ; Female ; *Health Knowledge, Attitudes, Practice ; Humans ; Male ; Middle Aged ; *Patient Acceptance of Health Care/statistics & numerical data ; *Socioeconomic Factors ; Time Factors ; Tuberculosis/*diagnosis/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: To assess patient delay in seeking tuberculosis diagnosis and associated factors in Hadiya Zone, Southern Ethiopia.

RESULTS: The median patient delay in tuberculosis diagnosis in Hadiya Zone was found to be 30 days. Socioeconomic and perception related factors were identified as independent predictors for tuberculosis diagnosis delay. Socioeconomic characteristics like urban residence [OR 2.36; CI 1.64-3.40], religious views [OR 1.24; CI 1.73-7.0], low monthly income [OR 3.38; CI 2.01-5.66] were statistically significantly associated with patient delay in tuberculosis diagnosis. On the other hand, attitudinal determinants such as misconception about the time of TB treatment to be cured and lack of comfort with directly observed treatment short course service [OR 1.54; CI 1.02-2.30] were identified as independent predictors of patient delay in tuberculosis diagnosis. Thus, there is a need for more robust information dissemination strategy to ultimately change people's views that tuberculosis can only be cured when diagnosed and treated promptly.}, } @article {pmid29426368, year = {2018}, author = {Sharp, C and Golubchik, T and Gregory, WF and McNaughton, AL and Gow, N and Selvaratnam, M and Mirea, A and Foster, D and Andersson, M and Klenerman, P and Jeffery, K and Matthews, PC}, title = {Oxford Screening CSF and Respiratory samples ('OSCAR'): results of a pilot study to screen clinical samples from a diagnostic microbiology laboratory for viruses using Illumina next generation sequencing.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {120}, pmid = {29426368}, issn = {1756-0500}, support = {//Wellcome Trust/United Kingdom ; 110110//Wellcome Trust/United Kingdom ; }, mesh = {Cerebrospinal Fluid/*virology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Metagenomics/*methods ; Pilot Projects ; Sequence Analysis, DNA/*methods ; Sputum/*virology ; }, abstract = {OBJECTIVES: There is increasing interest in the use of metagenomic (next generation sequencing, NGS) approaches for diagnosis of infection. We undertook a pilot study to screen samples submitted to a diagnostic microbiology laboratory in a UK teaching hospital using Illumina HiSeq. In the short-term, this small dataset provides insights into the virome of human respiratory and cerebrospinal fluid (CSF) samples. In the longer term, assimilating metagenomic data sets of this nature can inform optimization of laboratory and bioinformatic methods, and develop foundations for the interpretation of results in a clinical context. The project underpins a larger ongoing effort to develop NGS pipelines for diagnostic use.

DATA DESCRIPTION: Our data comprise a complete metagenomic dataset from 20 independent samples (10 CSF and 10 respiratory) submitted to the clinical microbiology laboratory for a large UK teaching hospital (Oxford University Hospitals NHS Foundation Trust). Sequences have been uploaded to the European Nucleotide Archive and are also presented as Krona plots through which the data can be interactively visualized. In the longer term, further optimization is required to better define sensitivity and specificity of this approach to clinical samples.}, } @article {pmid29426366, year = {2018}, author = {Kabalo, MY and Yohannes, B}, title = {Children with oedema recover better than those with severe wasting in outpatient therapeutic program at Boloso Sore district, Southwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {118}, pmid = {29426366}, issn = {1756-0500}, mesh = {Acute Disease ; Ambulatory Care/*statistics & numerical data ; Child Nutrition Disorders/epidemiology/*therapy ; Child, Preschool ; Edema/epidemiology/*therapy ; Ethiopia/epidemiology ; Female ; Humans ; Infant ; Male ; Outcome Assessment (Health Care)/*statistics & numerical data ; Outpatients ; Retrospective Studies ; Severity of Illness Index ; Wasting Syndrome/epidemiology/*therapy ; }, abstract = {OBJECTIVES: Severely undernourished young children clinically present with a typical nutritional oedema or none-oedematous. However, research evidence is limited on how these types predict treatment outcomes in Ethiopia. This study was aimed to compare oedematous and none-oedematous children for their treatment outcomes in Boloso Sore district in Southwest Ethiopia.

RESULTS: The overall recovery rate was 396 (68%). From oedematous children; 235 (79.9%) recovered, 18 (6.1%) transferred, 6 (2.0%) defaulted, 3 (1.0%) died, and 32 (11%) remained none-respondents. The treatment outcomes among the none-oedematous children were 161 (55.9%), 12 (4.2%), 4 (1.4%), 3 (1.0%), and 108 (37.5%) in similar order. Treatment outcomes of severely undernourished children in the two arms were statistically different (Χ2 = 5.82, P < 0.016). Severely malnourished children with oedema were 2.3 times highly likely to recover as compared to those without it (adjusted hazard ratio = 2.3 at 95% confidence interval: 1.79, 2.82). We documented that oedematous children in the study area had a better likelihood of recovery as compared to those with severe wasting. We recommend targeted community outreach activities on severe acute malnutrition focusing on the types.}, } @article {pmid29426365, year = {2018}, author = {Brüne, D and Andrade-Navarro, MA and Mier, P}, title = {Proteome-wide comparison between the amino acid composition of domains and linkers.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {117}, pmid = {29426365}, issn = {1756-0500}, mesh = {*Amino Acid Sequence ; Archaea ; Bacteria ; *Catalytic Domain ; Eukaryota ; *Proteome ; Proteomics/*methods ; *Sequence Analysis, Protein ; }, abstract = {OBJECTIVE: Amino acid composition is a sequence feature that has been extensively used to characterize proteomes of many species and protein families. Yet the analysis of amino acid composition of protein domains and the linkers connecting them has received less attention. Here, we perform both a comprehensive full-proteome amino acid composition analysis and a similar analysis focusing on domains and linkers, to uncover domain- or linker-specific differential amino acid usage patterns.

RESULTS: The amino acid composition in the 38 proteomes studied showcase the greater variability found in archaea and bacteria species compared to eukaryotes. When focusing on domains and linkers, we describe the preferential use of polar residues in linkers and hydrophobic residues in domains. To let any user perform this analysis on a given domain (or set of them), we developed a dedicated R script called RACCOON, which can be easily used and can provide interesting insights into the compositional differences between a domain and its surrounding linkers.}, } @article {pmid29426363, year = {2018}, author = {Ji, P and Rhoads, WJ and Edwards, MA and Pruden, A}, title = {Effect of heat shock on hot water plumbing microbiota and Legionella pneumophila control.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {30}, pmid = {29426363}, issn = {2049-2618}, support = {CBET Award #1336650//National Science Foundation/International ; }, mesh = {Amoebozoa/classification/*isolation & purification/microbiology ; DNA, Bacterial/genetics ; DNA, Protozoan/genetics ; DNA, Ribosomal/genetics ; Hot Temperature ; Legionella pneumophila/classification/growth & development/*isolation & purification ; RNA, Ribosomal, 16S/*genetics ; Sanitary Engineering ; Sequence Analysis, DNA/*methods ; Water Microbiology ; }, abstract = {BACKGROUND: Heat shock is a potential control strategy for Legionella pneumophila in hot water plumbing systems. However, it is not consistently effective, with little understanding of its influence on the broader plumbing microbiome. Here, we employed a lab-scale recirculating hot water plumbing rig to compare the pre- and post-"heat shock" (i.e., 40 → 60 → 40 °C) microbiota at distal taps. In addition, we used a second plumbing rig to represent a well-managed system at 60 °C and conducted a "control" sampling at 60 °C, subsequently reducing the temperature to 40 °C to observe the effects on Legionella and the microbiota under a simulated "thermal disruption" scenario.

RESULTS: According to 16S rRNA gene amplicon sequencing, in the heat shock scenario, there was no significant difference or statistically significant, but small, difference in the microbial community composition at the distal taps pre- versus post-heat shock (both biofilm and water; weighted and unweighted UniFrac distance matrices). While heat shock did lead to decreased total bacteria numbers at distal taps, it did not measurably alter the richness or evenness of the microbiota. Quantitative PCR measurements demonstrated that L. pneumophila relative abundance at distal taps also was not significantly different at 2-month post-heat shock relative to the pre-heat shock condition, while relative abundance of Vermamoeba vermiformis, a known Legionella host, did increase. In the thermal disruption scenario, relative abundance of planktonic L. pneumophila (quantitative PCR data) increased to levels comparable to those observed in the heat shock scenario within 2 months of switching long-term operation at 60 to 40 °C. Overall, water use frequency and water heater temperature set point exhibited a stronger effect than one-time heat shock on the microbial composition and Legionella levels at distal taps.

CONCLUSIONS: While heat shock may be effective for instantaneous Legionella control and reduction in total bacteria numbers, water heater temperature set point and water use frequency are more promising factors for long-term Legionella and microbial community control, illustrating the importance of maintaining consistent elevated temperatures in the system relative to short-term heat shock.}, } @article {pmid29426362, year = {2018}, author = {Kita, D and Kinumatsu, T and Yokomizo, A and Tanaka, M and Egawa, M and Makino-Oi, A and Tomita, S and Saito, A}, title = {Clinical effect of a dentifrice containing three kinds of bactericidal ingredients on periodontal disease: a pilot study in patients undergoing supportive periodontal therapy.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {116}, pmid = {29426362}, issn = {1756-0500}, mesh = {Adult ; Aged ; Anti-Bacterial Agents/administration & dosage/*pharmacology ; Dentifrices/*therapeutic use ; Female ; Gingival Crevicular Fluid/*immunology ; Humans ; Male ; Middle Aged ; Periodontitis/*diagnosis/*drug therapy ; Pilot Projects ; Treatment Outcome ; }, abstract = {OBJECTIVE: This study aimed to evaluate clinically the effect of a novel dentifrice containing three kinds of bactericidal ingredients on periodontal disease.

RESULTS: This was a single-arm, prospective clinical study that enrolled patients with periodontitis undergoing supportive periodontal therapy. Periodontal examination, microbiological testing of saliva samples, and evaluation of inflammatory markers (IL-1β, IL-6, IL-8, TNF-α) in gingival crevicular fluid were performed. After 4 weeks of the use of test dentifrice, these parameters were re-evaluated. The use of dentifrice was also subjectively evaluated by clinicians and participants. Among 30 participants, there were significant improvements in the periodontal and microbiological parameters, and the level of interleukin-1β in the gingival crevicular fluid, following the use of the test dentifrice. In clinicians' subjective evaluation of the overall usefulness of the dentifrice, 'mild' and 'moderate' improvement accounted for 83% of the total responses. In the participants' subjective evaluation, the majority indicated their experience of the use as favorable. Within the limitations of this study, it is suggested that the progression of periodontal disease during the supportive periodontal therapy can be prevented by the use of the test dentifrice. Trial registration UMIN Clinical Trials Registry (UMIN-CTR) 000023175. Date of formal registration: July 14, 2016 (https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000026716).}, } @article {pmid29426356, year = {2018}, author = {Wiweko, B and Indra, I and Susanto, C and Natadisastra, M and Hestiantoro, A}, title = {The correlation between serum AMH and HOMA-IR among PCOS phenotypes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {114}, pmid = {29426356}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Anti-Mullerian Hormone/*blood ; Female ; Humans ; Indonesia ; Insulin Resistance/*physiology ; Phenotype ; Polycystic Ovary Syndrome/*blood/*classification/pathology/physiopathology ; Young Adult ; }, abstract = {BACKGROUND: Polycystic ovarian syndrome (PCOS) is known to be one of the most prevalent endocrine disorders affecting reproductive age women. One of the endocrine disorder is hyperinsulinemia, which corresponds with the severity of PCOS. However, the pathogenesis of PCOS is not fully understood, but one theory of anti-mullerian hormone (AMH) has been proposed as one of the factor related to the degree of severity of PCOS. However, there are no clear correlation between levels of AMH with the incidence of insulin resistance in PCOS patients especially in Indonesia.

METHODS: This is a cross-sectional study involving reproductive age women aged 18-35 years. Subjects were recruited consecutively at Dr. Cipto Mangunkusumo General Hospital between 2011 until 2014. PCOS women diagnosed using 2003 Rotterdam criteria were categorized into four different PCOS phenotypes. Subsequently, serum level of AMH and HOMA-IR was measured and evaluated with correlation tests performed using SPSS 11.0 RESULTS: A total of 125 PCOS patients were included in a study conducted within a 3-year period. Phenotype 1 (anovulation, hyperandrogenism, and polycystic ovaries) shows the highest levels of AMH and HOMA-IR, which decreases in accordance to severity level (p < 0.005). The positive correlation between AMH and HOMA-IR persisted even after adjusting for BMI in multivariate analysis.

CONCLUSIONS: There was a positive correlation between serum AMH and HOMA IR levels. Serum AMH and HOMA IR levels were significantly different across the four PCOS phenotypes; with the highest values were present with phenotype 1.}, } @article {pmid29426290, year = {2018}, author = {Kebede, AZ and Johnston, A and Schneiderman, D and Bosnich, W and Harris, LJ}, title = {Transcriptome profiling of two maize inbreds with distinct responses to Gibberella ear rot disease to identify candidate resistance genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {131}, pmid = {29426290}, issn = {1471-2164}, support = {J-000008//Agriculture and Agri-Food Canada/International ; }, mesh = {Disease Resistance/*genetics ; Fusarium/physiology ; Gene Expression Regulation, Plant ; Gene Ontology ; Genes, Plant/genetics ; Gibberella/physiology ; High-Throughput Nucleotide Sequencing ; Host-Pathogen Interactions ; Inbreeding ; Plant Diseases/*genetics/microbiology ; Quantitative Trait Loci/genetics ; Species Specificity ; *Transcriptome ; Zea mays/classification/*genetics/microbiology ; }, abstract = {BACKGROUND: Gibberella ear rot (GER) is one of the most economically important fungal diseases of maize in the temperate zone due to moldy grain contaminated with health threatening mycotoxins. To develop resistant genotypes and control the disease, understanding the host-pathogen interaction is essential.

RESULTS: RNA-Seq-derived transcriptome profiles of fungal- and mock-inoculated developing kernel tissues of two maize inbred lines were used to identify differentially expressed transcripts and propose candidate genes mapping within GER resistance quantitative trait loci (QTL). A total of 1255 transcripts were significantly (P ≤ 0.05) up regulated due to fungal infection in both susceptible and resistant inbreds. A greater number of transcripts were up regulated in the former (1174) than the latter (497) and increased as the infection progressed from 1 to 2 days after inoculation. Focusing on differentially expressed genes located within QTL regions for GER resistance, we identified 81 genes involved in membrane transport, hormone regulation, cell wall modification, cell detoxification, and biosynthesis of pathogenesis related proteins and phytoalexins as candidate genes contributing to resistance. Applying droplet digital PCR, we validated the expression profiles of a subset of these candidate genes from QTL regions contributed by the resistant inbred on chromosomes 1, 2 and 9.

CONCLUSION: By screening global gene expression profiles for differentially expressed genes mapping within resistance QTL regions, we have identified candidate genes for gibberella ear rot resistance on several maize chromosomes which could potentially lead to a better understanding of Fusarium resistance mechanisms.}, } @article {pmid29426289, year = {2018}, author = {Wang, JR and Holt, J and McMillan, L and Jones, CD}, title = {FMLRC: Hybrid long read error correction using an FM-index.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {50}, pmid = {29426289}, issn = {1471-2105}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; DEB-1457707//National Science Foundation/International ; 2013-MRG-1110//North Carolina Biotechnology Center/International ; T32DK007737-17S1/DK/NIDDK NIH HHS/United States ; P50 GM076468/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Databases, Genetic ; Genome, Fungal ; Saccharomyces cerevisiae/genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Long read sequencing is changing the landscape of genomic research, especially de novo assembly. Despite the high error rate inherent to long read technologies, increased read lengths dramatically improve the continuity and accuracy of genome assemblies. However, the cost and throughput of these technologies limits their application to complex genomes. One solution is to decrease the cost and time to assemble novel genomes by leveraging "hybrid" assemblies that use long reads for scaffolding and short reads for accuracy.

RESULTS: We describe a novel method leveraging a multi-string Burrows-Wheeler Transform with auxiliary FM-index to correct errors in long read sequences using a set of complementary short reads. We demonstrate that our method efficiently produces significantly more high quality corrected sequence than existing hybrid error-correction methods. We also show that our method produces more contiguous assemblies, in many cases, than existing state-of-the-art hybrid and long-read only de novo assembly methods.

CONCLUSION: Our method accurately corrects long read sequence data using complementary short reads. We demonstrate higher total throughput of corrected long reads and a corresponding increase in contiguity of the resulting de novo assemblies. Improved throughput and computational efficiency than existing methods will help better economically utilize emerging long read sequencing technologies.}, } @article {pmid29426285, year = {2018}, author = {Dickinson, SE and Griffin, BA and Elmore, MF and Kriese-Anderson, L and Elmore, JB and Dyce, PW and Rodning, SP and Biase, FH}, title = {Transcriptome profiles in peripheral white blood cells at the time of artificial insemination discriminate beef heifers with different fertility potential.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {129}, pmid = {29426285}, issn = {1471-2164}, mesh = {Animals ; Breeding ; Cattle ; Female ; Fertility/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Insemination, Artificial/*veterinary ; Leukocytes/*metabolism ; Male ; Pregnancy ; Pregnancy Outcome/veterinary ; Red Meat/*standards ; Time Factors ; *Transcriptome ; }, abstract = {BACKGROUND: Infertility is a longstanding limitation in livestock production with important economic impact for the cattle industry. Female reproductive traits are polygenic and lowly heritable in nature, thus selection for fertility is challenging. Beef cattle operations leverage estrous synchronization in combination with artificial insemination (AI) to breed heifers and benefit from an early and uniform calving season. A couple of weeks following AI, heifers are exposed to bulls for an opportunity to become pregnant by natural breeding (NB), but they may also not become pregnant during this time period. Focusing on beef heifers, in their first breeding season, we hypothesized that: a- at the time of AI, the transcriptome of peripheral white blood cells (PWBC) differs between heifers that become pregnant to AI and heifers that become pregnant late in the breeding season by NB or do not become pregnant during the breeding season; and b- the ratio of transcript abundance between genes in PWBC classifies heifers according to pregnancy by AI, NB, or failure to become pregnant.

RESULTS: We generated RNA-sequencing data from 23 heifers from two locations (A: six AI-pregnant and five NB-pregnant; and B: six AI-pregnant and six non-pregnant). After filtering out lowly expressed genes, we quantified transcript abundance for 12,538 genes. The comparison of gene expression levels between AI-pregnant and NB-pregnant heifers yielded 18 differentially expressed genes (DEGs) (ADAM20, ALDH5A1, ANG, BOLA-DQB, DMBT1, FCER1A, GSTM3, KIR3DL1, LOC107131247, LOC618633, LYZ, MNS1, P2RY12, PPP1R1B, SIGLEC14, TPPP, TTLL1, UGT8, eFDR≤0.02). The comparison of gene expression levels between AI-pregnant and non-pregnant heifers yielded six DEGs (ALAS2, CNKSR3, LOC522763, SAXO2, TAC3, TFF2, eFDR≤0.05). We calculated the ratio of expression levels between all gene pairs and assessed their potential to classify samples according to experimental groups. Considering all samples, relative expression from two gene pairs correctly classified 10 out of 12 AI-pregnant heifers (P = 0.0028) separately from the other 11 heifers (NB-pregnant, or non-pregnant).

CONCLUSION: The transcriptome profile in PWBC, at the time of AI, is associated with the fertility potential of beef heifers. Transcript levels of specific genes may be further explored as potential classifiers, and thus selection tools, of heifer fertility.}, } @article {pmid29426284, year = {2018}, author = {Wan, Y and Mao, M and Wan, D and Yang, Q and Yang, F and Mandlaa, and Li, G and Wang, R}, title = {Identification of the WRKY gene family and functional analysis of two genes in Caragana intermedia.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {31}, pmid = {29426284}, issn = {1471-2229}, support = {31360169//National Natural Science Foundation of China/International ; 201503004//Inner Mongolia Science & Technology Plan/International ; }, mesh = {Caragana/*genetics/metabolism ; Multigene Family/*genetics ; Stress, Physiological/*genetics ; Transcription Factors/*genetics/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: WRKY transcription factors, one of the largest families of transcriptional regulators in plants, play important roles in plant development and various stress responses. The WRKYs of Caragana intermedia are still not well characterized, although many WRKYs have been identified in various plant species.

RESULTS: We identified 53 CiWRKY genes from C. intermedia transcriptome data, 28 of which exhibited complete open reading frames (ORFs). These CiWRKYs were divided into three groups via phylogenetic analysis according to their WRKY domains and zinc finger motifs. Conserved domain analysis showed that the CiWRKY proteins contain a highly conserved WRKYGQK motif and two variant motifs (WRKYGKK and WKKYEEK). The subcellular localization of CiWRKY26 and CiWRKY28-1 indicated that these two proteins localized exclusively to nuclei, supporting their role as transcription factors. The expression patterns of the 28 CiWRKYs with complete ORFs were examined through quantitative real-time PCR (qRT-PCR) in various tissues and under different abiotic stresses (drought, cold, salt, high-pH and abscisic acid (ABA)). The results showed that each CiWRKY responded to at least one stress treatment. Furthermore, overexpression of CiWRKY75-1 and CiWRKY40-4 in Arabidopsis thaliana suppressed the drought stress tolerance of the plants and delayed leaf senescence, respectively.

CONCLUSIONS: Fifty-three CiWRKY genes from the C. intermedia transcriptome were identified and divided into three groups via phylogenetic analysis. The expression patterns of the 28 CiWRKYs under different abiotic stresses suggested that each CiWRKY responded to at least one stress treatment. Overexpression of CiWRKY75-1 and CiWRKY40-4 suppressed the drought stress tolerance of Arabidopsis and delayed leaf senescence, respectively. These results provide a basis for the molecular mechanism through which CiWRKYs mediate stress tolerance.}, } @article {pmid29426279, year = {2018}, author = {Versteeg, B and Bruisten, SM and Pannekoek, Y and Jolley, KA and Maiden, MCJ and van der Ende, A and Harrison, OB}, title = {Genomic analyses of the Chlamydia trachomatis core genome show an association between chromosomal genome, plasmid type and disease.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {130}, pmid = {29426279}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; 104992//Wellcome Trust (GB)/International ; H2RXJo00//Oxford Martin School, University of Oxford (GB)/International ; }, mesh = {Chlamydia Infections/microbiology ; Chlamydia trachomatis/classification/*genetics/physiology ; Chromosomes, Bacterial/*genetics ; Genes, Bacterial/genetics ; Genetic Variation ; Genome, Bacterial/*genetics ; Genomics/*methods ; Humans ; Phylogeny ; Plasmids/*genetics ; Species Specificity ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: Chlamydia trachomatis (Ct) plasmid has been shown to encode genes essential for infection. We evaluated the population structure of Ct using whole-genome sequence data (WGS). In particular, the relationship between the Ct genome, plasmid and disease was investigated.

RESULTS: WGS data from 157 Ct isolates deposited in the Chlamydiales pubMLST database (http://pubMLST.org/chlamydiales/) were annotated with 902 genes including the core and accessory genome. Plasmid associated genes were annotated and a plasmid MLST scheme was defined allowing plasmid sequence types to be determined. Plasmid allelic variation was investigated. Phylogenetic relationships were examined using the Genome Comparator tool available in pubMLST. Phylogenetic analyses identified four distinct Ct core genome clusters and six plasmid clusters, with a strong association between the chromosomal genotype and plasmid. This in turn was linked to ompA genovars and disease phenotype. Horizontal genetic transfer of plasmids was observed for three urogenital-associated isolates, which possessed plasmids more commonly found in isolates resulting from ocular infections. The pgp3 gene was identified as the most polymorphic plasmid gene and pgp4 was the most conserved.

CONCLUSION: A strong association between chromosomal genome, plasmid type and disease was observed, consistent with previous studies. This suggests co-evolution of the Ct chromosome and their plasmids, but we confirmed that plasmid transfer can occur between isolates. These data provide a better understanding of the genetic diversity occurring across the Ct genome in association with the plasmid content.}, } @article {pmid29426277, year = {2018}, author = {Tian, S and Kou, Y and Zhang, Z and Yuan, L and Li, D and López-Pujol, J and Fan, D and Zhang, Z}, title = {Phylogeography of Eomecon chionantha in subtropical China: the dual roles of the Nanling Mountains as a glacial refugium and a dispersal corridor.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {20}, pmid = {29426277}, issn = {1471-2148}, support = {41061006//National Natural Science Foundation of China/International ; 31560064//National Natural Science Foundation of China/International ; }, mesh = {Base Sequence ; Bayes Theorem ; China ; Chloroplasts/genetics ; DNA, Chloroplast/genetics ; DNA, Plant/genetics ; DNA, Ribosomal Spacer/genetics ; *Ecosystem ; Genetic Variation ; Geography ; Haplotypes/genetics ; *Ice Cover ; Microsatellite Repeats/genetics ; Papaveraceae/*classification/genetics ; Phylogeny ; *Phylogeography ; *Refugium ; Sample Size ; *Tropical Climate ; }, abstract = {BACKGROUND: Mountains have not only provided refuge for species, but also offered dispersal corridors during the Neogene and Quaternary global climate changes. Compared with a plethora of studies on the refuge role of China's mountain ranges, their dispersal corridor role has received little attention in plant phylogeographic studies. Using phylogeographic data of Eomecon chionantha Hance (Papaveraceae), this study explicitly tested whether the Nanling Mountains, which spans from west to east for more than 1000 km in subtropical China, could have functioned as a dispersal corridor during the late Quaternary in addition to a glacial refugium.

RESULTS: Our analyses revealed a range-wide lack of phylogeographic structure in E. chionantha across three kinds of molecular markers [two chloroplast intergenic spacers, nuclear ribosomal internal transcribed spacer (nrITS), and six nuclear microsatellite loci]. Demographic inferences based on chloroplast and nrITS sequences indicated that E. chionantha could have experienced a strong postglacial range expansion between 6000 and 1000 years ago. Species distribution modelling showed that the Nanling Mountains and the eastern Yungui Plateau were the glacial refugia of E. chionantha. Reconstruction of dispersal corridors indicated that the Nanling Mountains also have acted as a corridor of population connectivity for E. chionantha during the late Quaternary.

CONCLUSIONS: Our results suggest that the Nanling Mountains may acted dual roles as a dispersal corridor in east-west direction and as a glacial refugium in subtropical China during the late Quaternary. The population connectivity mediated by the mountain range and a strong postglacial range expansion are the most likely reasons for the lack of phylogeographic structure in E. chionantha. The hypothesis of dual roles of the mountain range presented here sheds new insights into the phylogeographic patterns of organisms in subtropical China.}, } @article {pmid29425311, year = {2018}, author = {Potapova, NA and Andrianova, MA and Bazykin, GA and Kondrashov, AS}, title = {Are Nonsense Alleles of Drosophila melanogaster Genes under Any Selection?.}, journal = {Genome biology and evolution}, volume = {10}, number = {4}, pages = {1012-1018}, pmid = {29425311}, issn = {1759-6653}, mesh = {Alleles ; Alternative Splicing/genetics ; Amino Acid Sequence ; Animals ; Codon, Nonsense/*genetics ; Drosophila melanogaster/*genetics ; *Evolution, Molecular ; Exons ; Genetics, Population ; Pseudogenes ; Selection, Genetic/*genetics ; }, abstract = {A gene which carries a bona fide loss-of-function mutation effectively becomes a functionless pseudogene, free from selective constraint. However, there is a number of molecular mechanisms that may lead to at least a partial preservation of the function of genes carrying even drastic alleles. We performed a direct measurement of the strength of negative selection acting on nonsense alleles of protein-coding genes in the Zambian population of Drosophila melanogaster. Within those exons that carry nonsense mutations, negative selection, assayed by the ratio of missense over synonymous nucleotide diversity levels, appears to be absent, consistent with total loss of function. In other exons of nonsense alleles, negative selection was deeply relaxed but likely not completely absent, and the per site number of missense alleles declined significantly with the distance from the premature stop codon. This pattern may be due to alternative splicing which preserves function of some isoforms of nonsense alleles of genes.}, } @article {pmid29425255, year = {2017}, author = {Kirchengast, S}, title = {Response to Lea et al.'s developmental plasticity: Bridging research in evolution and human health.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {181-182}, pmid = {29425255}, issn = {2050-6201}, } @article {pmid29424840, year = {2017}, author = {Watve, M}, title = {Developmental plasticity: Need to go beyond naïve thinking.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {178-180}, pmid = {29424840}, issn = {2050-6201}, } @article {pmid29424839, year = {2017}, author = {Michels, KB}, title = {Developmental plasticity: Friend or foe?.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {183-184}, pmid = {29424839}, issn = {2050-6201}, abstract = {Developmental plasticity - the concept that adaptation to changing and unfavorable environmental conditions are possible but may come at the price of compromised health potentials - has evolutionary grounding as it facilitates survival but dissents with fundamental evolutionary principles in that it may advance the lesser fit. It is an important cornerstone of the Developmental Origins of Health and Disease (DOHaD). Unlike evolutionary adaptation developmental plasticity may be short-lived and restricted to one or few generations and inheritance is uncertain. Potential mechanisms include epigenetic modifications adopted in utero which may not transmit to the next generation; future insights may allow adjustments of the outcomes of developmental plasticity.}, } @article {pmid29424836, year = {2017}, author = {Stearns, S}, title = {Epigenetic reaction norms: possible but not inevitable.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {176-177}, pmid = {29424836}, issn = {2050-6201}, } @article {pmid29424834, year = {2017}, author = {Lea, AJ and Tung, J and Archie, EA and Alberts, SC}, title = {Developmental plasticity: Bridging research in evolution and human health.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {162-175}, pmid = {29424834}, issn = {2050-6201}, support = {P01 AG031719/AG/NIA NIH HHS/United States ; P30 AG034424/AG/NIA NIH HHS/United States ; R01 AG053330/AG/NIA NIH HHS/United States ; }, abstract = {Early life experiences can have profound and persistent effects on traits expressed throughout the life course, with consequences for later life behavior, disease risk, and mortality rates. The shaping of later life traits by early life environments, known as 'developmental plasticity', has been well-documented in humans and non-human animals, and has consequently captured the attention of both evolutionary biologists and researchers studying human health. Importantly, the parallel significance of developmental plasticity across multiple fields presents a timely opportunity to build a comprehensive understanding of this phenomenon. We aim to facilitate this goal by highlighting key outstanding questions shared by both evolutionary and health researchers, and by identifying theory and empirical work from both research traditions that is designed to address these questions. Specifically, we focus on: (i) evolutionary explanations for developmental plasticity, (ii) the genetics of developmental plasticity and (iii) the molecular mechanisms that mediate developmental plasticity. In each section, we emphasize the conceptual gains in human health and evolutionary biology that would follow from filling current knowledge gaps using interdisciplinary approaches. We encourage researchers interested in developmental plasticity to evaluate their own work in light of research from diverse fields, with the ultimate goal of establishing a cross-disciplinary understanding of developmental plasticity.}, } @article {pmid29424833, year = {2017}, author = {Wells, JCK}, title = {Understanding developmental plasticity as adaptation requires an inter-generational perspective.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {185-187}, pmid = {29424833}, issn = {2050-6201}, abstract = {In this issue of Evolution, Medicine and Public Health, Lea and colleagues argue that there are major advantages to bringing together biomedical and evolutionary perspectives on plasticity. To develop this approach, they propose two contrasting scenarios for 'developmental plasticity as adaptation': that it reflects adjustments to resolve the effects of early 'constraints', or that it adjusts phenotype to ecological cues in anticipation of similar conditions in adulthood. Yet neither scenario highlights the unique role of maternal phenotype, mediated by maternal investment strategy, in generating such constraints or cues. Developmental plasticity is greatest during the period when all ecological influences on the offspring are transduced by maternal phenotype. If the offspring adapts during this period, then the target of that adaptation is to maternal phenotype. Ignoring the inter-generational source of early constraints or cues prevents development of a comprehensive adaptive framework, because developmental plasticity is fundamentally relevant to the fitness of both offspring and parents.}, } @article {pmid29424472, year = {2018}, author = {Giovannotti, M and Nisi Cerioni, P and Rojo, V and Olmo, E and Slimani, T and Splendiani, A and Caputo Barucchi, V}, title = {Characterization of a satellite DNA in the genera Lacerta and Timon (Reptilia, Lacertidae) and its role in the differentiation of the W chromosome.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {2}, pages = {83-95}, doi = {10.1002/jez.b.22790}, pmid = {29424472}, issn = {1552-5015}, mesh = {Animals ; Base Sequence ; DNA, Satellite/*genetics ; Female ; Genetic Variation ; In Situ Hybridization, Fluorescence ; Lizards/*genetics ; Male ; Phylogeography ; Sex Chromosomes/*genetics ; }, abstract = {In this study, IMO-TaqI satDNA, previously isolated in several species of Lacertidae, was isolated and characterized from four species of the genus Lacerta and three of the genus Timon. The aim was to gain further insights into the evolutionary dynamics of this satDNA, its occurrence among lacertids and to understand if it plays any role in sex chromosome evolution in these seven species. The results here obtained highlighted the presence of this repetitive element in the genome of all the species investigated, thus indicating that IMO-TaqI satDNA is evolutionary conserved among a wide variety of lacertids. In addition, this element was found to be very abundant in the constitutive heterochromatin of the W-sex chromosome of the four Lacerta species investigated. The occurrence of IMO-TaqI satDNA on Lacerta heterochromosome suggests that it is involved in the differentiation of the W chromosome by heterochromatinization, and the fact that it is absent in the W of other lacertids investigated seems to confirm that repetitive DNA sequences would remain randomly trapped into the sex chromosomes, undergoing amplification as a consequence of the suppression of recombination.}, } @article {pmid29424462, year = {2018}, author = {de Jong, MA and Saastamoinen, M}, title = {Environmental and genetic control of cold tolerance in the Glanville fritillary butterfly.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {5}, pages = {636-645}, pmid = {29424462}, issn = {1420-9101}, abstract = {Thermal tolerance has a major effect on individual fitness and species distributions and can be determined by genetic variation and phenotypic plasticity. We investigate the effects of developmental and adult thermal conditions on cold tolerance, measured as chill coma recovery (CCR) time, during the early and late adult stage in the Glanville fritillary butterfly. We also investigate the genetic basis of cold tolerance by associating CCR variation with polymorphisms in candidate genes that have a known role in insect physiology. Our results demonstrate that a cooler developmental temperature leads to reduced cold tolerance in the early adult stage, whereas cooler conditions during the adult stage lead to increased cold tolerance. This suggests that adult acclimation, but not developmental plasticity, of adult cold tolerance is adaptive. This could be explained by the ecological conditions the Glanville fritillary experiences in the field, where temperature during early summer, but not spring, is predictive of thermal conditions during the butterfly's flight season. In addition, an amino acid polymorphism (Ala-Glu) in the gene flightin, which has a known function in insect flight and locomotion, was associated with CCR. These amino acids have distinct biochemical properties and may thus affect protein function and/or structure. To our knowledge, our study is the first to link genetic variation in flightin to cold tolerance, or thermal adaptation in general.}, } @article {pmid29423730, year = {2018}, author = {Lewis, GL and Jorgensen, QR and Loy, JD and Moxley, RA}, title = {Tellurite Resistance in Shiga Toxin-Producing Escherichia coli.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {752-759}, pmid = {29423730}, issn = {1432-0991}, support = {2012-68003-30155//National Institute of Food and Agriculture/ ; }, mesh = {Microbial Sensitivity Tests ; Shiga-Toxigenic Escherichia coli/*drug effects/*genetics ; Tellurium/*pharmacology ; }, abstract = {Potassium tellurite (K2TeO3) is an effective selective agent for O157:H7 Shiga toxin-producing Escherichia coli (STEC), whereas tellurite resistance in non-O157 STEC is variable with information on O45 minimal. High-level K2TeO3 resistance in STEC is attributable to the ter gene cluster with terD an indicator of the cluster's presence. Polymerase chain reactions for terD and K2TeO3 minimum inhibitory concentration (MIC) determinations in broth cultures were conducted on 70 STEC and 40 non-STEC control organisms. Sixty-six STEC strains (94.3%) were terD+ compared to 28 control organisms (70.0%; P < 0.001). The prevalence of terD in O103 STEC strains was 70%, whereas in all other serogroups it was ≥ 90%. The K2TeO3 geometric mean MIC ranking for STEC serogroups from highest to lowest was O111 > O26 > O145 > O157 > O103 > O121 = O45. The K2TeO3 geometric mean MIC was significantly higher in terD+ than in terD- STEC, but not in terD+ versus terD- control strains. Resistance to K2TeO3 (MIC ≥ 25 mg/L) was exhibited by 65/66 terD+ and 0/4 terD- STEC strains, compared to 12/28 terD+ and 8/12 terD- control strains. These results confirm previous studies showing the significantly higher prevalence of the ter gene cluster in STEC strains, and the relationship between these genes and K2TeO3 resistance in STEC and especially intimin (eae)-positive STEC, in contrast to non-STEC organisms. O45 and O121 STEC, although frequently terD positive, on average had significantly lower levels of K2TeO3 resistance than O26, O111, and O145 STEC.}, } @article {pmid29423729, year = {2018}, author = {Nguyen, D and Ely, B}, title = {A Genome Comparison of T7-like Podoviruses That Infect Caulobacter crescentus.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {760-765}, pmid = {29423729}, issn = {1432-0991}, support = {R25GM076277//National Institute of General Medical Sciences/ ; }, mesh = {Caulobacter crescentus/*virology ; DNA, Viral/genetics ; DNA-Directed RNA Polymerases/genetics ; Genome, Viral/*genetics ; Phylogeny ; Podoviridae/*genetics/*pathogenicity ; Viral Proteins/genetics ; }, abstract = {Bacteriophages remain an understudied component of bacterial communities. Therefore, our laboratory has initiated an effort to isolate large numbers of bacteriophages that infect Caulobacter crescentus to provide an estimate of the diversity of bacteriophages that infect this common environmental bacterium. The majority of the new isolates are phicbkviruses, a genus of giant viruses that appear to be Caulobacter specific. However, we have also isolated several Podoviruses with icosahedral heads and small tails. One of these Podoviruses, designated Lullwater, is similar to two previously isolated Caulobacter phages, Cd1 and Percy. All three have genomes that are approximately 45 kb and contain approximately 30 genes. The gene order is conserved among the three genomes with one of the genes coding for a DNA polymerase that has homology to the family of T7 DNA polymerases. Phylogenetic trees based on either the DNA polymerase or the RNA polymerase amino acid sequences suggests that the three phages represent a new branch of the T7virus tree. Based on these similarities, we concluded that Cd1, Lullwater, and Percy comprise a new group in the T7virus genus.}, } @article {pmid29423654, year = {2018}, author = {Parzer, HF and David Polly, P and Moczek, AP}, title = {The evolution of relative trait size and shape: insights from the genitalia of dung beetles.}, journal = {Development genes and evolution}, volume = {228}, number = {2}, pages = {83-93}, pmid = {29423654}, issn = {1432-041X}, support = {0718522//National Science Foundation/International ; 0445661//National Science Foundation/International ; }, mesh = {Animals ; *Biological Evolution ; Body Size ; Coleoptera/*anatomy & histology/*genetics ; *Genetic Variation ; Genitalia/anatomy & histology/physiology ; Male ; Phenotype ; Phylogeny ; Quantitative Trait, Heritable ; Reproduction ; }, abstract = {Insects show relatively little genital variation within species compared to extraordinary and often rapid diversification among species. It has been suggested that selection for reproductive isolation through differences in genital shape might explain this phenomenon. This hypothesis predicts that populations diverge faster in genital shape than in genital size. We tested this prediction in males from 10 dung beetle species with known phylogenetic relationships from the genus Onthophagus (Coleoptera: Scarabaeidae), including four species for which we were able to sample multiple populations. Specifically, we compared intra- and interspecific differentiation in shape and relative sizes of genitalia and calculated their respective evolutionary rates. We compared these rates to two similarly sized non-genital traits, the head and the fore-tibia. We found significant intraspecific variation in genital shape in all four species for which multiple populations were sampled, but for three of them we also identified significant relative size variation. We also found that genital shape evolved at higher rates than relative genital size. Genital shape evolved faster than head shape, but not fore-tibia shape. However, shapes of all measured structures evolved faster than their relative size. We discuss the functional constraints that may bias the developmental evolution of relative size and shape of genitalia and other morphological traits.}, } @article {pmid29423226, year = {2018}, author = {Bayersdorf, R and Fruscalzo, A and Catania, F}, title = {Linking autoimmunity to the origin of the adaptive immune system.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {2-12}, pmid = {29423226}, issn = {2050-6201}, abstract = {In jawed vertebrates, the adaptive immune system (AIS) cooperates with the innate immune system (IIS) to protect hosts from infections. Although targeting non-self-components, the AIS also generates self-reactive antibodies which, when inadequately counter-selected, can give rise to autoimmune diseases (ADs). ADs are on the rise in western countries. Why haven't ADs been eliminated during the evolution of a ∼500 million-year old system? And why have they become more frequent in recent decades? Self-recognition is an attribute of the phylogenetically more ancient IIS and empirical data compellingly show that some self-reactive antibodies, which are classifiable as elements of the IIS rather then the AIS, may protect from (rather than cause) ADs. Here, we propose that the IIS's self-recognition system originally fathered the AIS and, as a consequence of this relationship, its activity is dampened in hygienic environments. Rather than a mere breakdown or failure of the mechanisms of self-tolerance, ADs might thus arise from architectural constraints.}, } @article {pmid29423225, year = {2017}, author = {Wells, JCK and Figueiroa, JN and Alves, JG}, title = {Maternal pelvic dimensions and neonatal size: Implications for growth plasticity in early life as adaptation.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {191-200}, pmid = {29423225}, issn = {2050-6201}, abstract = {Patterns of fetal growth predict non-communicable disease risk in adult life, but fetal growth variability appears to have a relatively weak association with maternal nutritional dynamics during pregnancy. This challenges the interpretation of fetal growth variability as 'adaptation'. We hypothesized that associations of maternal size and nutritional status with neonatal size are mediated by the dimensions of the maternal pelvis. We analysed data on maternal height, body mass index (BMI) and pelvic dimensions (conjugate, inter-spinous and inter-cristal diameters) and neonatal gestational age, weight, length, thorax girth and head girth (n = 224). Multiple regression analysis was used to identify independent maternal predictors of neonatal size, and the mediating role of neonatal head girth in these associations. Pelvic dimensions displaced maternal BMI as a predictor of birth weight, explaining 11.6% of the variance. Maternal conjugate and inter-spinous diameters predicted neonatal length, thorax girth and head girth, whereas inter-cristal diameter only predicted neonatal length. Associations of pelvic dimensions with birth length, but not birth weight, were mediated by neonatal head girth. Pelvic dimensions predicted neonatal size better than maternal BMI, and these associations were mostly independent of maternal height. Sensitivity of fetal growth to pelvic dimensions reduces the risk of cephalo-pelvic disproportion, potentially a strong selective pressure during secular trends in height. Selection on fetal adaptation to relatively inflexible components of maternal phenotype, rather than directly to external ecological conditions, may help explain high levels of growth plasticity during late fetal life and early infancy.}, } @article {pmid29423224, year = {2017}, author = {Kuzawa, CW}, title = {Which environments matter in studies of early life developmental plasticity?.}, journal = {Evolution, medicine, and public health}, volume = {2017}, number = {1}, pages = {188-190}, pmid = {29423224}, issn = {2050-6201}, } @article {pmid29422444, year = {2018}, author = {Nowak, BF and Archibald, JM}, title = {Opportunistic but Lethal: The Mystery of Paramoebae.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {404-419}, doi = {10.1016/j.pt.2018.01.004}, pmid = {29422444}, issn = {1471-5007}, support = {//CIHR/Canada ; }, mesh = {Amoebozoa/*parasitology/pathogenicity ; Animals ; Eukaryota/*physiology ; Parasitic Diseases, Animal/parasitology ; Research/trends ; *Symbiosis ; }, abstract = {Paramoebae are enigmatic single-celled eukaryotes that can be opportunistic pathogens of marine animals. For example, amoebic gill disease ravages farmed salmonids worldwide, causing tens of millions of dollars in losses annually. Although paramoebae can be found associated with animals ranging from fish and lobster to molluscs and sea urchins, how and how often they actually cause disease is unknown. Here we review recent progress towards understanding the biology and ecology of paramoebid species and the eukaryotic endosymbionts that live inside them. Genomic and transcriptomic sequence data serve as a platform upon which future research on paramoebiasis can build.}, } @article {pmid29422443, year = {2018}, author = {Candido, RRF and St Pierre, TG and Morassutti, AL and Graeff-Teixeira, C and Jones, MK}, title = {Eggs and Magnetism: New Approaches for Schistosomiasis Diagnosis.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {267-271}, doi = {10.1016/j.pt.2018.01.003}, pmid = {29422443}, issn = {1471-5007}, mesh = {Animals ; Diagnostic Techniques and Procedures/trends ; Humans ; *Magnetics ; Ovum/chemistry ; Parasitology/*methods ; Schistosoma/*chemistry ; Schistosomiasis/*diagnosis ; }, abstract = {To date, reliable techniques that can provide accurate information on the local and global prevalence of schistosomiasis are still associated with high costs or labour-intensive processes. Here we discuss old and new concepts for diagnostic approaches, and we highlight structural properties of schistosome eggshells that result in their affinity for magnetic materials as a new diagnostic approach.}, } @article {pmid29422349, year = {2018}, author = {Rockström, J and Richardson, K and Steffen, W and Mace, G}, title = {Planetary Boundaries: Separating Fact from Fiction. A Response to Montoya et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {233-234}, doi = {10.1016/j.tree.2018.01.010}, pmid = {29422349}, issn = {1872-8383}, } @article {pmid29422348, year = {2018}, author = {Germanov, ES and Marshall, AD and Bejder, L and Fossi, MC and Loneragan, NR}, title = {Microplastics: No Small Problem for Filter-Feeding Megafauna.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {227-232}, doi = {10.1016/j.tree.2018.01.005}, pmid = {29422348}, issn = {1872-8383}, mesh = {Animals ; *Environmental Exposure ; *Feeding Behavior ; Oceans and Seas ; Plastics/*adverse effects ; *Sharks ; *Skates (Fish) ; Water Pollutants/*adverse effects ; *Whales ; }, abstract = {Microplastic pollution can impact filter-feeding marine megafauna, namely mobulid rays, filter-feeding sharks, and baleen whales. Emerging research on these flagship species highlights potential exposure to microplastic contamination and plastic-associated toxins. Research and its wide communication are needed to understand the magnitude of the issue and improve marine stewardship.}, } @article {pmid29422347, year = {2018}, author = {Montoya, JM and Donohue, I and Pimm, SL}, title = {Why a Planetary Boundary, If It Is Not Planetary, and the Boundary Is Undefined? A Reply to Rockström et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {234}, doi = {10.1016/j.tree.2018.01.008}, pmid = {29422347}, issn = {1872-8383}, } @article {pmid29422108, year = {2018}, author = {Roy, DK and Cohen, S and Singh, VP and Marla, V and Ghimire, S}, title = {Endodontic management of mandibular canine with two roots and two canals: a rare case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {111}, pmid = {29422108}, issn = {1756-0500}, mesh = {Cuspid/*anatomy & histology/diagnostic imaging ; Female ; Humans ; Middle Aged ; Periodontitis/diagnosis/therapy ; Pulpitis/diagnosis/therapy ; Root Canal Therapy ; Tooth Root/*anatomy & histology/diagnostic imaging ; }, abstract = {BACKGROUND: In general, mandibular canines have a single root and a single canal. The occurrence of two roots and two canals is a rare entity ranging from 1 to 5%. The anatomy of root canal morphology plays a decisive role in determining the conditions under which endodontic treatment can be performed effectively. Successful endodontic treatment comprises proper diagnosis, meticulous cleaning and shaping followed by three dimensional obturation. Failure to do so may lead to postoperative diseases, pain and further complications. This paper reports successful management of a mandibular canine with two roots and two canals.

CASE PRESENTATION: 45-year-old Nepalese women with a non-significant medical history presented with a chief complaint of pain in a lower left front tooth. The pain disturbed her sleep and lingered for several minutes even after removal of a thermal stimulus. Clinical examination and testing revealed generalized severe attrition with tenderness to percussion in the mandibular left canine. Electric pulp test for all the mandibular anteriors revealed almost no response in the mandibular left canine. Intraoral periapical radiographs in different angulations were taken which revealed two roots and two canals. A clinical diagnosis of chronic irreversible pulpitis with symptomatic apical periodontitis was made and root canal therapy was performed following the standard protocols.

CONCLUSION: Although the prevalence of two roots and two canals in mandibular canine is very low, the clinician should always be mindful of variations in the number of roots and canals for proper management of such cases.}, } @article {pmid29422101, year = {2018}, author = {Tiller, NB and Simpson, AJ}, title = {Effect of spirometry on intra-thoracic pressures.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {110}, pmid = {29422101}, issn = {1756-0500}, mesh = {Adult ; Esophagus/physiology ; Exhalation/*physiology ; Humans ; Inhalation/*physiology ; Male ; *Maximal Respiratory Pressures ; *Spirometry ; Young Adult ; }, abstract = {OBJECTIVE: Due to the high intra-thoracic pressures associated with forced vital capacity manoeuvres, spirometry is contraindicated for vulnerable patients. However, the typical pressure response to spirometry has not been reported. Eight healthy, recreationally-active men performed spirometry while oesophageal pressure was recorded using a latex balloon-tipped catheter.

RESULTS: Peak oesophageal pressure during inspiration was - 47 ± 9 cmH2O (37 ± 10% of maximal inspiratory pressure), while peak oesophageal pressure during forced expiration was 102 ± 34 cmH2O (75 ± 17% of maximal expiratory pressure). The deleterious consequences of spirometry might be associated with intra-thoracic pressures that approach maximal values during forced expiration.}, } @article {pmid29422086, year = {2018}, author = {Adams, Y and Ofori, EK and Asare-Anane, H and Amanquah, SD and Ababio, GK and Abendau, E and Nabia, R}, title = {Adipocytokines in obese Ghanaian subjects with or without type 2 diabetes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {109}, pmid = {29422086}, issn = {1756-0500}, mesh = {Adult ; *C-Reactive Protein ; Comorbidity ; Diabetes Mellitus, Type 2/*blood/epidemiology ; Female ; Ghana/epidemiology ; Humans ; Leptin/*blood ; Male ; Middle Aged ; Obesity/*blood/epidemiology ; }, abstract = {OBJECTIVE: This study aimed to evaluate serum leptin and high sensitivity C-reactive protein (hsCRP) concentrations in obese Ghanaians with or without type 2 diabetes and to find out the extent to which their levels are influenced by underlying disorders.

RESULTS: Obese subjects with type 2 diabetes had lower leptin but higher hsCRP levels compared with obese non-diabetic controls. There were negative correlations within the control group for glucose vs % muscle mass (r = - 0.378, p = 0.016), leptin vs % muscle mass (r = - 0.555, p = 0.001) and within the obese diabetic group for leptin vs % muscle mass (r = - 0.602, p = 0.001). Obese persons without diabetes were about three times more likely to have higher leptin levels compared with their obese diabetic counterparts (Odds ratio = 3.315, p < 0.001). Obese females independently had a tenfold increase in leptin levels compared with obese males.}, } @article {pmid29422083, year = {2018}, author = {Ansumana, R and Dariano, DF and Jacobsen, KH and Leski, TA and Lamin, JM and Lahai, J and Bangura, U and Bockarie, AS and Taitt, CR and Yasuda, C and Bockarie, MJ and Stenger, DA}, title = {Seroprevalence of hepatitis B surface antigen (HBsAg) in Bo, Sierra Leone, 2012-2013.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {113}, pmid = {29422083}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Child ; Child, Preschool ; Female ; Fever/*blood ; Hepatitis B Surface Antigens/*blood ; Hepatitis B, Chronic/*prevention & control ; Humans ; Male ; Middle Aged ; Prevalence ; Seroepidemiologic Studies ; Sierra Leone/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: The aim of this study was to determine the prevalence of hepatitis B surface antigen (HBsAg) among febrile individuals tested at Mercy Hospital Research Laboratory (MHRL) in Bo, Sierra Leone.

RESULTS: A total of 860 febrile individuals ages 5 years and older were tested by MHRL between July 2012 and June 2013 with a Standard Diagnostics Bioline HBsAg rapid diagnostic test. The overall HBsAg prevalence rate was 13.7%, including a rate of 15.5% among males and 12.6% among females. The HBsAg rate did not differ by child or adult age group (p > 0.5). The prevalence rate in Bo was similar to the 11-15% HBsAg prevalence rates reported in the past decade from other studies across West Africa. Scaling up the infant hepatitis B vaccination program in Sierra Leone will be important for reducing the future burden of disease and premature death attributable to chronic viral hepatitis B disease.}, } @article {pmid29422081, year = {2018}, author = {Abera, T and Bitew, M and Gebre, D and Mamo, Y and Deneke, Y and Nandi, S}, title = {Bluetongue disease in small ruminants in south western Ethiopia: cross-sectional sero-epidemiological study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {112}, pmid = {29422081}, issn = {1756-0500}, support = {annual research Grant//Jimma University/ ; 2015/16//Jimma University/ ; }, mesh = {Age Factors ; Animals ; Bluetongue/*blood/epidemiology ; Bluetongue virus/*immunology ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Goat Diseases/*blood/epidemiology ; Goats ; Male ; Seroepidemiologic Studies ; Sheep ; }, abstract = {OBJECTIVE: The status of bluetongue disease, vectors for transmission of the disease and the serotypes involved are not clearly known in Ethiopia. This sero-epidemiological study was conducted to determine the seroprevalence and associated risk factors of bluetongue in small ruminants of South Western Ethiopia.

RESULT: 422 serum samples were screened for the presence of bluetongue virus (BTV) specific antibodies using competitive enzyme-linked immunosorbent assay (c-ELISA) and 30.6% (129/422) (confidence interval CI 26.2-35%) of the sheep and goat serum samples were found positive. Multivariate analysis of several risk factors like age, sex, altitude, body condition and species of animals were studied and it was observed that species of animals, age and altitude had significant influence (P < 0.05) on seropositivity to BTV. Goats showed more seropositivity to bluetongue as compared to sheep [AOR = 2.4, 95% CI (1.5-3.9), P = 0.001], adult animals were more seropositive [AOR = 3.1, 95% CI (1.9-5.1), P = 0.001] than other age groups and animals at the lowland [AOR = 3.1, 95% CI (1.5-6.4), P = 0.002] showed more seropositivity to bluetongue than midland and high land. Sex and body condition of the animals had no statistically significant (P > 0.05) effect on seropositivity to bluetongue.}, } @article {pmid29422035, year = {2018}, author = {Zhong, Y and Zhang, X and Cheng, ZM}, title = {Lineage-specific duplications of NBS-LRR genes occurring before the divergence of six Fragaria species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {128}, pmid = {29422035}, issn = {1471-2164}, support = {31501737//the National Natural Science Foundation of China/International ; 31570368//the National Natural Science Foundation of China/International ; KJQN201655//the Fundamental Research Funds for the Central Universities/International ; ZW201711//the open funds of the State Key Laboratory of Crop Genetics and Germplasm Enhancement/International ; }, mesh = {Biological Evolution ; Chromosome Mapping ; Computational Biology/methods ; Databases, Genetic ; Disease Resistance/*genetics ; Fragaria/classification/*genetics ; *Gene Duplication ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; *Genetic Linkage ; Host-Pathogen Interactions/genetics ; Multigene Family ; Phylogeny ; Plant Diseases/etiology/genetics ; Plant Proteins/*genetics ; Species Specificity ; Transcriptome ; }, abstract = {BACKGROUND: Plant disease resistance (R) genes are evolving rapidly and play a critical role in the innate immune system of plants. The nucleotide binding sites-leucine rich repeat (NBS-LRR) genes are one of the largest classes in plant R genes. Previous studies have focused on the NBS-LRR genes from one or several species of different genera, and the sequenced genomes of the genus Fragaria offer the opportunity to study the evolutionary processes of these R genes among the closely related species.

RESULTS: In this study, 325, 155, 190, 187, and 133 NBS-LRRs were discovered from F. x ananassa, F. iinumae, F. nipponica, F. nubicola, and F. orientalis, respectively. Together with the 144 NBS-LRR genes from F. vesca, a total of 1134 NBS-LRRs containing 866 multi-genes comprised 184 gene families across the six Fragaria genomes. Extremely short branch lengths and shallow nodes were widely present in the phylogenetic tree constructed with all of the NBS-LRR genes of the six strawberry species. The identities of the orthologous genes were highly significantly greater than those of the paralogous genes, while the Ks ratios of the former were very significantly lower than those of the latter in all of the NBS-LRR gene families. In addition, the Ks and Ka/Ks values of the TIR-NBS-LRR genes (TNLs) were significantly greater than those of the non-TIR-NBS-LRR genes (non-TNLs). Furthermore, the expression patterns of the NBS-LRR genes revealed that the same gene expressed differently under different genetic backgrounds in response to pathogens.

CONCLUSIONS: These results, combined with the shared hotspot regions of the duplicated NBS-LRRs on the chromosomes, indicated that the lineage-specific duplication of the NBS-LRR genes occurred before the divergence of the six Fragaria species. The Ks and Ka/Ks ratios suggested that the TNLs are more rapidly evolving and driven by stronger diversifying selective pressures than the non-TNLs.}, } @article {pmid29422031, year = {2018}, author = {Sun, C and Galicia, C and Stenkamp, DL}, title = {Transcripts within rod photoreceptors of the Zebrafish retina.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {127}, pmid = {29422031}, issn = {1471-2164}, support = {P20 RR016454/RR/NCRR NIH HHS/United States ; R01 EY012146/EY/NEI NIH HHS/United States ; R21 EY026814/EY/NEI NIH HHS/United States ; S10 OD018044/OD/NIH HHS/United States ; }, mesh = {Animals ; Computational Biology/methods ; Fluorescent Antibody Technique ; Gene Expression Profiling ; Gene Library ; Gene Ontology ; High-Throughput Nucleotide Sequencing ; Molecular Sequence Annotation ; Regeneration ; Retina/*cytology/metabolism/pathology ; Retinal Degeneration/genetics/metabolism/pathology ; Retinal Rod Photoreceptor Cells/*metabolism ; *Transcriptome ; Zebrafish/*genetics ; }, abstract = {BACKGROUND: The purpose of this study was to identify transcripts of retinal rod photoreceptors of the zebrafish. The zebrafish is an important animal model for vision science due to rapid and tractable development, persistent neurogenesis of rods throughout the lifespan, and capacity for functional retinal regeneration.

RESULTS: Zebrafish rods, and non-rod retinal cells of the xops:eGFP transgenic line, were separated by cell dissociation and fluorescence-activated cell sorting (FACS), followed by RNA-seq. At a false discovery rate of < 0.01, 597 transcripts were upregulated ("enriched") in rods vs. other retinal cells, and 1032 were downregulated ("depleted"). Thirteen thousand three hundred twenty four total transcripts were detected in rods, including many not previously known to be expressed by rods. Forty five transcripts were validated by qPCR in FACS-sorted rods vs. other retinal cells. Transcripts enriched in rods from adult retinas were also enriched in rods from larval and juvenile retinas, and were also enriched in rods sorted from retinas subjected to a neurotoxic lesion and allowed to regenerate. Many transcripts enriched in rods were upregulated in retinas of wildtype retinas vs. those of a zebrafish model for rod degeneration.

CONCLUSIONS: We report the generation and validation of an RNA-seq dataset describing the rod transcriptome of the zebrafish, which is now available as a resource for further studies of rod photoreceptor biology and comparative transcriptomics.}, } @article {pmid29422030, year = {2018}, author = {Zhang, Y and Liu, J and Liu, X and Fan, X and Hong, Y and Wang, Y and Huang, Y and Xie, M}, title = {Prioritizing disease genes with an improved dual label propagation framework.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {47}, pmid = {29422030}, issn = {1471-2105}, support = {No. 61702367//National Natural Science Foundation of China (CN)/International ; 2017KJ033//The Research Project of Tianjin Municipal Commission of Education/International ; }, mesh = {*Algorithms ; Area Under Curve ; Computational Biology/*methods ; Disease/*genetics ; Humans ; Parkinson Disease/genetics ; Phenotype ; Protein Interaction Maps/genetics ; Statistics as Topic ; }, abstract = {BACKGROUND: Prioritizing disease genes is trying to identify potential disease causing genes for a given phenotype, which can be applied to reveal the inherited basis of human diseases and facilitate drug development. Our motivation is inspired by label propagation algorithm and the false positive protein-protein interactions that exist in the dataset. To the best of our knowledge, the false positive protein-protein interactions have not been considered before in disease gene prioritization. Label propagation has been successfully applied to prioritize disease causing genes in previous network-based methods. These network-based methods use basic label propagation, i.e. random walk, on networks to prioritize disease genes in different ways. However, all these methods can not deal with the situation in which plenty false positive protein-protein interactions exist in the dataset, because the PPI network is used as a fixed input in previous methods. This important characteristic of data source may cause a large deviation in results.

RESULTS: A novel network-based framework IDLP is proposed to prioritize candidate disease genes. IDLP effectively propagates labels throughout the PPI network and the phenotype similarity network. It avoids the method falling when few disease genes are known. Meanwhile, IDLP models the bias caused by false positive protein interactions and other potential factors by treating the PPI network matrix and the phenotype similarity matrix as the matrices to be learnt. By amending the noises in training matrices, it improves the performance results significantly. We conduct extensive experiments over OMIM datasets, and IDLP has demonstrated its effectiveness compared with eight state-of-the-art approaches. The robustness of IDLP is also validated by doing experiments with disturbed PPI network. Furthermore, We search the literatures to verify the predicted new genes got by IDLP are associated with the given diseases, the high prediction accuracy shows IDLP can be a powerful tool to help biologists discover new disease genes.

CONCLUSIONS: IDLP model is an effective method for disease gene prioritization, particularly for querying phenotypes without known associated genes, which would be greatly helpful for identifying disease genes for less studied phenotypes.

AVAILABILITY: https://github.com/nkiip/IDLP.}, } @article {pmid29422028, year = {2018}, author = {Pirson, M and Clippe, A and Knoops, B}, title = {The curious case of peroxiredoxin-5: what its absence in aves can tell us and how it can be used.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {18}, pmid = {29422028}, issn = {1471-2148}, support = {816844//DIANE research program of the Walloon region/International ; #10/15-026//Communauté française de Belgique - Actions de Recherche Concertées (ARC)/International ; }, mesh = {Amino Acid Sequence ; Animals ; Blotting, Western ; Cell Line, Tumor ; Chickens/*metabolism ; Conserved Sequence ; Cysteine/metabolism ; Electroporation ; Humans ; Peroxidases/genetics ; Peroxiredoxins/chemistry/*metabolism ; Sequence Homology, Amino Acid ; Subcellular Fractions/metabolism ; }, abstract = {BACKGROUND: Peroxiredoxins are ubiquitous thiol-dependent peroxidases that represent a major antioxidant defense in both prokaryotic cells and eukaryotic organisms. Among the six vertebrate peroxiredoxin isoforms, peroxiredoxin-5 (PRDX5) appears to be a particular peroxiredoxin, displaying a different catalytic mechanism, as well as a wider substrate specificity and subcellular distribution. In addition, several evolutionary peculiarities, such as loss of subcellular targeting in certain species, have been reported for this enzyme.

RESULTS: Western blotting analyses of 2-cys PRDXs (PRDX1-5) failed to identify the PRDX5 isoform in chicken tissue homogenates. Thereafter, via in silico analysis of PRDX5 orthologs, we went on to show that the PRDX5 gene is conserved in all branches of the amniotes clade, with the exception of aves. Further investigation of bird genomic sequences and expressed tag sequences confirmed the disappearance of the gene, though TRMT112, a gene located closely to the 5' extremity of the PRDX5 gene, is conserved. Finally, using in ovo electroporation to overexpress the long and short forms of human PRDX5, we showed that, though the gene is lost in birds, subcellular targeting of human PRDX5 is conserved in the chick.

CONCLUSIONS: Further adding to the distinctiveness of this enzyme, this study reports converging evidence supporting loss of PRDX5 in aves. In-depth analysis revealed that this absence is proper to birds as PRDX5 appears to be conserved in non-avian amniotes. Finally, taking advantage of the in ovo electroporation technique, we validate the subcellular targeting of human PRDX5 in the chick embryo and bring forward this gain-of-function model as a potent way to study PRDX5 functions in vivo.}, } @article {pmid29422027, year = {2018}, author = {Mozere, M and Tekman, M and Kari, J and Bockenhauer, D and Kleta, R and Stanescu, H}, title = {OVAS: an open-source variant analysis suite with inheritance modelling.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {46}, pmid = {29422027}, issn = {1471-2105}, support = {2012-305608//European Union FP7/International ; }, mesh = {Databases, Genetic ; *Genetic Variation ; Humans ; Inheritance Patterns/*genetics ; Internet ; *Models, Genetic ; Molecular Sequence Annotation ; Mutation/genetics ; *Software ; User-Computer Interface ; Web Browser ; }, abstract = {BACKGROUND: The advent of modern high-throughput genetics continually broadens the gap between the rising volume of sequencing data, and the tools required to process them. The need to pinpoint a small subset of functionally important variants has now shifted towards identifying the critical differences between normal variants and disease-causing ones. The ever-increasing reliance on cloud-based services for sequence analysis and the non-transparent methods they utilize has prompted the need for more in-situ services that can provide a safer and more accessible environment to process patient data, especially in circumstances where continuous internet usage is limited.

RESULTS: To address these issues, we herein propose our standalone Open-source Variant Analysis Sequencing (OVAS) pipeline; consisting of three key stages of processing that pertain to the separate modes of annotation, filtering, and interpretation. Core annotation performs variant-mapping to gene-isoforms at the exon/intron level, append functional data pertaining the type of variant mutation, and determine hetero/homozygosity. An extensive inheritance-modelling module in conjunction with 11 other filtering components can be used in sequence ranging from single quality control to multi-file penetrance model specifics such as X-linked recessive or mosaicism. Depending on the type of interpretation required, additional annotation is performed to identify organ specificity through gene expression and protein domains. In the course of this paper we analysed an autosomal recessive case study. OVAS made effective use of the filtering modules to recapitulate the results of the study by identifying the prescribed compound-heterozygous disease pattern from exome-capture sequence input samples.

CONCLUSION: OVAS is an offline open-source modular-driven analysis environment designed to annotate and extract useful variants from Variant Call Format (VCF) files, and process them under an inheritance context through a top-down filtering schema of swappable modules, run entirely off a live bootable medium and accessed locally through a web-browser.}, } @article {pmid29422024, year = {2018}, author = {Platt, A and Weber, CC and Liberles, DA}, title = {Protein evolution depends on multiple distinct population size parameters.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {17}, pmid = {29422024}, issn = {1471-2148}, support = {1515704//Division of Biological Infrastructure/International ; }, mesh = {*Evolution, Molecular ; Genetics, Population ; Mutation/genetics ; *Population Density ; Proteins/*genetics ; Selection, Genetic ; }, abstract = {That population size affects the fate of new mutations arising in genomes, modulating both how frequently they arise and how efficiently natural selection is able to filter them, is well established. It is therefore clear that these distinct roles for population size that characterize different processes should affect the evolution of proteins and need to be carefully defined. Empirical evidence is consistent with a role for demography in influencing protein evolution, supporting the idea that functional constraints alone do not determine the composition of coding sequences.Given that the relationship between population size, mutant fitness and fixation probability has been well characterized, estimating fitness from observed substitutions is well within reach with well-formulated models. Molecular evolution research has, therefore, increasingly begun to leverage concepts from population genetics to quantify the selective effects associated with different classes of mutation. However, in order for this type of analysis to provide meaningful information about the intra- and inter-specific evolution of coding sequences, a clear definition of concepts of population size, what they influence, and how they are best parameterized is essential.Here, we present an overview of the many distinct concepts that "population size" and "effective population size" may refer to, what they represent for studying proteins, and how this knowledge can be harnessed to produce better specified models of protein evolution.}, } @article {pmid29421312, year = {2018}, author = {Sayyari, E and Whitfield, JB and Mirarab, S}, title = {DiscoVista: Interpretable visualizations of gene tree discordance.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {110-115}, doi = {10.1016/j.ympev.2018.01.019}, pmid = {29421312}, issn = {1095-9513}, mesh = {Classification/*methods ; Genome ; Models, Genetic ; Phylogeny ; *Software ; }, abstract = {Phylogenomics has ushered in an age of discordance. Analyses often reveal abundant discordances among phylogenies of different parts of genomes, as well as incongruences between species trees obtained using different methods or data partitions. Researchers are often left trying to make sense of such incongruences. Interpretive ways of measuring and visualizing discordance are needed, both among alternative species trees and gene trees, especially for specific focal branches of a tree. Here, we introduce DiscoVista, a publicly available tool that creates a suite of simple but interpretable visualizations. DiscoVista helps quantify the amount of discordance and some of its potential causes.}, } @article {pmid29420807, year = {2018}, author = {Bourguignon, T and Tang, Q and Ho, SYW and Juna, F and Wang, Z and Arab, DA and Cameron, SL and Walker, J and Rentz, D and Evans, TA and Lo, N}, title = {Transoceanic Dispersal and Plate Tectonics Shaped Global Cockroach Distributions: Evidence from Mitochondrial Phylogenomics.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {970-983}, doi = {10.1093/molbev/msy013}, pmid = {29420807}, issn = {1537-1719}, abstract = {Following the acceptance of plate tectonics theory in the latter half of the 20th century, vicariance became the dominant explanation for the distributions of many plant and animal groups. In recent years, however, molecular-clock analyses have challenged a number of well-accepted hypotheses of vicariance. As a widespread group of insects with a fossil record dating back 300 My, cockroaches provide an ideal model for testing hypotheses of vicariance through plate tectonics versus transoceanic dispersal. However, their evolutionary history remains poorly understood, in part due to unresolved relationships among the nine recognized families. Here, we present a phylogenetic estimate of all extant cockroach families, as well as a timescale for their evolution, based on the complete mitochondrial genomes of 119 cockroach species. Divergence dating analyses indicated that the last common ancestor of all extant cockroaches appeared ∼235 Ma, ∼95 My prior to the appearance of fossils that can be assigned to extant families, and before the breakup of Pangaea began. We reconstructed the geographic ranges of ancestral cockroaches and found tentative support for vicariance through plate tectonics within and between several major lineages. We also found evidence of transoceanic dispersal in lineages found across the Australian, Indo-Malayan, African, and Madagascan regions. Our analyses provide evidence that both vicariance and dispersal have played important roles in shaping the distribution and diversity of these insects.}, } @article {pmid29420776, year = {2018}, author = {Otero-Bravo, A and Goffredi, S and Sabree, ZL}, title = {Cladogenesis and Genomic Streamlining in Extracellular Endosymbionts of Tropical Stink bugs.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29420776}, issn = {1759-6653}, abstract = {Phytophagous stink bugs are globally-distributed and many harbor vertically-inherited bacterial symbionts that are extracellular, yet little is known about how the symbiont's genomes have evolved under this transmission strategy. Genome reduction is common in insect intracellular symbionts but limited genome sampling of the extracellular symbionts of distantly-related stink bugs has precluded inferring patterns of extracellular symbiont genome evolution. To address this knowledge gap, we completely sequenced the genomes of the uncultivable bacterial symbionts of four neotropical stink bugs of the Edessa genus. Phylogenetic and comparative analyses indicated that the symbionts form a clade within the Pantoea genus and their genomes are highly-reduced (∼0.8 Mb). Furthermore, genome synteny analysis and a jackknife approach for phylogenetic reconstruction, which corrected for long branch attraction artifacts, indicated that the Edessa symbionts were the result of a single symbiotic event that was distinct from the symbiosis event giving rise to Candidatus "Pantoea carbekii", the extracellular symbiont of the invasive pentatomid stink bug, Halyomorpha halys. Metabolic functions inferred from the Edessa symbiont genomes suggests a shift in genomic composition characteristic of its lifestyle in that they retained many host-supportive functions while undergoing dramatic gene loss and establishing a stable relationship with their host insects. Given the undersampled nature of extracellular insect symbionts, this study is the first comparative analysis of these symbiont genomes from four distinct Edessa stink bug species. Finally, we propose the candidate name 'Candidatus Pantoea edessiphila' for the species of these symbionts with strain designations according to their host species.}, } @article {pmid29420738, year = {2018}, author = {Pan, S and Bruford, MW and Wang, Y and Lin, Z and Gu, Z and Hou, X and Deng, X and Dixon, A and Graves, JAM and Zhan, X}, title = {Transcription-Associated Mutation Promotes RNA Complexity in Highly Expressed Genes-A Major New Source of Selectable Variation.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1104-1119}, pmid = {29420738}, issn = {1537-1719}, abstract = {Alternatively spliced transcript isoforms are thought to play a critical role for functional diversity. However, the mechanism generating the enormous diversity of spliced transcript isoforms remains unknown, and its biological significance remains unclear. We analyzed transcriptomes in saker falcons, chickens, and mice to show that alternative splicing occurs more frequently, yielding more isoforms, in highly expressed genes. We focused on hemoglobin in the falcon, the most abundantly expressed genes in blood, finding that alternative splicing produces 10-fold more isoforms than expected from the number of splice junctions in the genome. These isoforms were produced mainly by alternative use of de novo splice sites generated by transcription-associated mutation (TAM), not by the RNA editing mechanism normally invoked. We found that high expression of globin genes increases mutation frequencies during transcription, especially on nontranscribed DNA strands. After DNA replication, transcribed strands inherit these somatic mutations, creating de novo splice sites, and generating multiple distinct isoforms in the cell clone. Bisulfate sequencing revealed that DNA methylation may counteract this process by suppressing TAM, suggesting DNA methylation can spatially regulate RNA complexity. RNA profiling showed that falcons living on the high Qinghai-Tibetan Plateau possess greater global gene expression levels and higher diversity of mean to high abundance isoforms (reads per kilobases per million mapped reads ≥18) than their low-altitude counterparts, and we speculate that this may enhance their oxygen transport capacity under low-oxygen environments. Thus, TAM-induced RNA diversity may be physiologically significant, providing an alternative strategy in lifestyle evolution.}, } @article {pmid29420719, year = {2018}, author = {Bernard, G and Pathmanathan, JS and Lannes, R and Lopez, P and Bapteste, E}, title = {Microbial Dark Matter Investigations: How Microbial Studies Transform Biological Knowledge and Empirically Sketch a Logic of Scientific Discovery.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {707-715}, pmid = {29420719}, issn = {1759-6653}, mesh = {Bacteria/*genetics ; *Genetic Variation ; *Metagenomics ; Phylogeny ; }, abstract = {Microbes are the oldest and most widespread, phylogenetically and metabolically diverse life forms on Earth. However, they have been discovered only 334 years ago, and their diversity started to become seriously investigated even later. For these reasons, microbial studies that unveil novel microbial lineages and processes affecting or involving microbes deeply (and repeatedly) transform knowledge in biology. Considering the quantitative prevalence of taxonomically and functionally unassigned sequences in environmental genomics data sets, and that of uncultured microbes on the planet, we propose that unraveling the microbial dark matter should be identified as a central priority for biologists. Based on former empirical findings of microbial studies, we sketch a logic of discovery with the potential to further highlight the microbial unknowns.}, } @article {pmid29420714, year = {2018}, author = {Metzger, DCH and Schulte, PM}, title = {The DNA Methylation Landscape of Stickleback Reveals Patterns of Sex Chromosome Evolution and Effects of Environmental Salinity.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {775-785}, pmid = {29420714}, issn = {1759-6653}, mesh = {Adaptation, Physiological/genetics ; Animals ; DNA Methylation/*genetics ; Epigenesis, Genetic ; *Evolution, Molecular ; Female ; Genome ; Male ; Phenotype ; Salinity ; Sex Chromosomes/*genetics ; Smegmamorpha/*genetics ; }, abstract = {Epigenetic mechanisms such as DNA methylation are a key component of dosage compensation on sex chromosomes and have been proposed as an important source of phenotypic variation influencing plasticity and adaptive evolutionary processes, yet little is known about the role of DNA methylation in an ecological or evolutionary context in vertebrates. The threespine stickleback (Gasterosteus aculeatus) is an ecological and evolutionary model system that has been used to study mechanisms involved in the evolution of adaptive phenotypes in novel environments as well as the evolution heteromorphic sex chromosomes and dosage compensation in vertebrates. Using whole genome bisulfite sequencing, we compared genome-wide DNA methylation patterns between threespine stickleback males and females and between stickleback reared at different environmental salinities. Apparent hypermethylation of the younger evolutionary stratum of the stickleback X chromosome in females relative to males suggests a potential role of DNA methylation in the evolution of heteromorphic sex chromosomes. We also demonstrate that rearing salinity has genome-wide effects on DNA methylation levels, which has the potential to lead to the accumulation of epigenetic variation between natural populations in different environments.}, } @article {pmid29420512, year = {2018}, author = {Foteinis, S}, title = {Bitcoin's alarming carbon footprint.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {169}, doi = {10.1038/d41586-018-01625-x}, pmid = {29420512}, issn = {1476-4687}, } @article {pmid29420511, year = {2018}, author = {Corkeron, P and Kraus, SD}, title = {Baleen whale species on brink of extinction for first time in 300 years.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {169}, doi = {10.1038/d41586-018-01672-4}, pmid = {29420511}, issn = {1476-4687}, mesh = {Animals ; Conservation of Natural Resources/*trends ; Endangered Species/*statistics & numerical data ; *Extinction, Biological ; Gulf of Mexico ; Petroleum Pollution/adverse effects ; Time Factors ; Whales/*classification ; }, } @article {pmid29420509, year = {2018}, author = {Ledford, H}, title = {Debate blooms over anatomy of the world's first flower.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {153-154}, doi = {10.1038/d41586-018-01539-8}, pmid = {29420509}, issn = {1476-4687}, mesh = {Biological Evolution ; *Flowers ; Fossils ; }, } @article {pmid29420508, year = {2018}, author = {}, title = {Restore justice in Turkey.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {145}, doi = {10.1038/d41586-018-01677-z}, pmid = {29420508}, issn = {1476-4687}, mesh = {*Politics ; Research Personnel/*legislation & jurisprudence ; Terrorism/legislation & jurisprudence ; Turkey ; Warfare ; }, } @article {pmid29420507, year = {2018}, author = {Fratzl, P}, title = {Wood made denser and stronger.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {172-173}, doi = {10.1038/d41586-018-01371-0}, pmid = {29420507}, issn = {1476-4687}, mesh = {Plant Stems ; *Trees ; *Wood ; }, } @article {pmid29420506, year = {2018}, author = {}, title = {Strategy for making safer opioids bolstered.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {181}, doi = {10.1038/d41586-018-01621-1}, pmid = {29420506}, issn = {1476-4687}, } @article {pmid29420505, year = {2018}, author = {Curry, S}, title = {Let's move beyond the rhetoric: it's time to change how we judge research.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {147}, doi = {10.1038/d41586-018-01642-w}, pmid = {29420505}, issn = {1476-4687}, mesh = {*Bibliometrics ; Journal Impact Factor ; Reproducibility of Results ; Research/*standards ; Research Personnel/*standards ; Reward ; }, } @article {pmid29420504, year = {2018}, author = {Dolgin, E}, title = {How going green can raise cash for your lab.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {265-267}, doi = {10.1038/d41586-018-01601-5}, pmid = {29420504}, issn = {1476-4687}, mesh = {Animals ; Budgets ; Carbon Footprint/economics ; Conservation of Energy Resources/economics/methods ; Cost Savings/economics/*methods ; Equipment and Supplies/*economics ; Financing, Organized/economics/organization & administration ; Indicators and Reagents/chemistry ; Internet ; Laboratories/*economics ; Laboratory Chemicals/economics ; Microscopy, Fluorescence/economics/instrumentation ; Motivation ; Pilot Projects ; Recycling/*economics/methods ; Research/*economics/*instrumentation ; Research Personnel/*economics/psychology ; }, } @article {pmid29420503, year = {2018}, author = {Biewener, AA}, title = {Evolutionary race as predators hunt prey.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {176-178}, doi = {10.1038/d41586-018-01278-w}, pmid = {29420503}, issn = {1476-4687}, mesh = {Animals ; *Biological Evolution ; *Predatory Behavior ; }, } @article {pmid29420502, year = {2018}, author = {Goodman, MF}, title = {Smoking gun for a rare mutation mechanism.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {180-181}, doi = {10.1038/d41586-018-00418-6}, pmid = {29420502}, issn = {1476-4687}, mesh = {DNA/*chemistry ; Mutation ; }, } @article {pmid29420501, year = {2018}, author = {Nordling, L}, title = {How decolonization could reshape South African science.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {159-162}, doi = {10.1038/d41586-018-01696-w}, pmid = {29420501}, issn = {1476-4687}, mesh = {African Continental Ancestry Group/education/*psychology/statistics & numerical data ; *Apartheid/economics/legislation & jurisprudence/psychology ; *Colonialism ; Cultural Characteristics ; *Cultural Diversity ; Educational Status ; European Continental Ancestry Group/psychology/statistics & numerical data ; Female ; Humans ; Male ; Racism ; Research Personnel/education/*psychology/statistics & numerical data/*trends ; Science/education/*trends ; Sexism ; Social Sciences ; Socioeconomic Factors ; South Africa ; Universities/organization & administration/trends ; Workforce ; }, } @article {pmid29420500, year = {2018}, author = {Wijers, R}, title = {A chirp, a roar and a whisper.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {178-179}, doi = {10.1038/d41586-018-01570-9}, pmid = {29420500}, issn = {1476-4687}, } @article {pmid29420498, year = {2018}, author = {Tollefson, J}, title = {UN agency targets black-carbon pollution from ships.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {155-156}, doi = {10.1038/d41586-018-01556-7}, pmid = {29420498}, issn = {1476-4687}, mesh = {Air Pollution/analysis ; Carbon ; Environmental Pollution ; *Ships ; *Soot ; United Nations ; Water Pollution ; }, } @article {pmid29420496, year = {2018}, author = {}, title = {Big data needs a hardware revolution.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {145-146}, doi = {10.1038/d41586-018-01683-1}, pmid = {29420496}, issn = {1476-4687}, mesh = {Artificial Intelligence/*trends ; Biomimetics ; Brain/physiology ; Computers/*trends ; Humans ; Public-Private Sector Partnerships ; Semiconductors/*trends ; }, } @article {pmid29420495, year = {2018}, author = {Wise, FW}, title = {Solitons divide and conquer.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {179-180}, doi = {10.1038/d41586-018-01470-y}, pmid = {29420495}, issn = {1476-4687}, } @article {pmid29420494, year = {2018}, author = {Sharma, AK}, title = {Don't belittle junior researchers in meetings.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {169}, doi = {10.1038/d41586-018-01676-0}, pmid = {29420494}, issn = {1476-4687}, mesh = {Age Factors ; *Communication ; Congresses as Topic ; *Formative Feedback ; Research Personnel/*psychology ; }, } @article {pmid29420492, year = {2018}, author = {Wright, G and Rochette, J and Gjerde, KM and Levin, LA}, title = {Protect the neglected half of our blue planet.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {163-165}, doi = {10.1038/d41586-018-01594-1}, pmid = {29420492}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms ; Conservation of Natural Resources/*legislation & jurisprudence ; *International Cooperation ; *Oceans and Seas ; Population Dynamics ; }, } @article {pmid29420491, year = {2018}, author = {}, title = {Maths classification is getting a revision.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {146}, doi = {10.1038/d41586-018-01690-2}, pmid = {29420491}, issn = {1476-4687}, } @article {pmid29420490, year = {2018}, author = {Parry, I}, title = {Fossil-fuel subsidies assessed.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {175-176}, doi = {10.1038/d41586-018-01495-3}, pmid = {29420490}, issn = {1476-4687}, mesh = {*Fossil Fuels ; }, } @article {pmid29420489, year = {2018}, author = {Vesper, I}, title = {Bulgaria in the cold as European Union freezes its innovation funding.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {156-157}, doi = {10.1038/d41586-018-01374-x}, pmid = {29420489}, issn = {1476-4687}, mesh = {Bulgaria ; European Union/*organization & administration ; Financing, Organized/*economics/*organization & administration ; Inventions/*economics ; Research/*economics ; Research Support as Topic/*economics/*legislation & jurisprudence ; }, } @article {pmid29420488, year = {2018}, author = {}, title = {The science that's never been cited.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {158}, doi = {10.1038/d41586-018-01687-x}, pmid = {29420488}, issn = {1476-4687}, } @article {pmid29420487, year = {2018}, author = {Zastrow, M}, title = {Kid co-authors in South Korea spur government probe.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {154-155}, doi = {10.1038/d41586-018-01512-5}, pmid = {29420487}, issn = {1476-4687}, mesh = {Adolescent ; *Authorship ; Competitive Behavior ; *Deception ; *Federal Government ; Humans ; *Parents ; Republic of Korea ; Research Personnel/*legislation & jurisprudence ; *School Admission Criteria ; Scientific Misconduct/*legislation & jurisprudence ; *Universities ; }, } @article {pmid29420486, year = {2018}, author = {Neff, M}, title = {Quest for publication metrics undermines regional research.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {169}, doi = {10.1038/d41586-018-01675-1}, pmid = {29420486}, issn = {1476-4687}, mesh = {Communication Barriers ; Ecology/*standards/*trends ; *Journal Impact Factor ; Mexico ; *Motivation ; Research/standards/*trends ; Reward ; }, } @article {pmid29420485, year = {2018}, author = {}, title = {Truck tracks, wolf lawsuit and a fertility first.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {150-151}, doi = {10.1038/d41586-018-01711-0}, pmid = {29420485}, issn = {1476-4687}, } @article {pmid29420484, year = {2018}, author = {Strassheim, S and Schenkel, W}, title = {Existing rules cover gene-drive applications.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {169}, doi = {10.1038/d41586-018-01623-z}, pmid = {29420484}, issn = {1476-4687}, } @article {pmid29420483, year = {2018}, author = {Callaway, E}, title = {Geneticists unravel secrets of super-invasive crayfish.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {157-158}, doi = {10.1038/d41586-018-01624-y}, pmid = {29420483}, issn = {1476-4687}, mesh = {Animals ; *Astacoidea ; *Introduced Species ; Physicians ; Seafood ; }, } @article {pmid29420482, year = {2018}, author = {Boon, S}, title = {Saving lives and property with accurate flood forecasts.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {267}, doi = {10.1038/d41586-018-01614-0}, pmid = {29420482}, issn = {1476-4687}, } @article {pmid29420481, year = {2018}, author = {Mardis, E}, title = {Many mutations in one clinical-trial basket.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {173-175}, doi = {10.1038/d41586-018-01312-x}, pmid = {29420481}, issn = {1476-4687}, mesh = {*Mutation ; }, } @article {pmid29420480, year = {2018}, author = {Bao, H and Das, D and Courtney, NA and Jiang, Y and Briguglio, JS and Lou, X and Roston, D and Cui, Q and Chanda, B and Chapman, ER}, title = {Dynamics and number of trans-SNARE complexes determine nascent fusion pore properties.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {260-263}, pmid = {29420480}, issn = {1476-4687}, support = {F32 GM112371/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 NS081293/NS/NINDS NIH HHS/United States ; R01 NS101723/NS/NINDS NIH HHS/United States ; R01 MH061876/MH/NIMH NIH HHS/United States ; R35 NS097362/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Botulinum Toxins, Type A/metabolism ; Cell Membrane/*metabolism ; Excitatory Postsynaptic Potentials ; *Exocytosis ; Lipid Bilayers/metabolism ; *Membrane Fusion ; Mice ; Neurons/cytology/metabolism ; Neurotransmitter Agents/metabolism ; *Porosity ; Rats ; Rats, Sprague-Dawley ; SNARE Proteins/*metabolism ; Secretory Vesicles/metabolism ; }, abstract = {The fusion pore is the first crucial intermediate formed during exocytosis, yet little is known about the mechanisms that determine the size and kinetic properties of these transient structures. Here, we reduced the number of available SNAREs (proteins that mediate vesicle fusion) in neurons and observed changes in transmitter release that are suggestive of alterations in fusion pores. To investigate these changes, we employed reconstituted fusion assays using nanodiscs to trap pores in their initial open state. Optical measurements revealed that increasing the number of SNARE complexes enhanced the rate of release from single pores and enabled the escape of larger cargoes. To determine whether this effect was due to changes in nascent pore size or to changes in stability, we developed an approach that uses nanodiscs and planar lipid bilayer electrophysiology to afford microsecond resolution at the single event level. Both pore size and stability were affected by SNARE copy number. Increasing the number of vesicle (v)-SNAREs per nanodisc from three to five caused a twofold increase in pore size and decreased the rate of pore closure by more than three orders of magnitude. Moreover, pairing of v-SNAREs and target (t)-SNAREs to form trans-SNARE complexes was highly dynamic: flickering nascent pores closed upon addition of a v-SNARE fragment, revealing that the fully assembled, stable SNARE complex does not form at this stage of exocytosis. Finally, a deletion at the base of the SNARE complex, which mimics the action of botulinum neurotoxin A, markedly reduced fusion pore stability. In summary, trans-SNARE complexes are dynamic, and the number of SNAREs recruited to drive fusion determines fundamental properties of individual pores.}, } @article {pmid29420479, year = {2018}, author = {Chiara, CJ and Carroll, JJ and Carpenter, MP and Greene, JP and Hartley, DJ and Janssens, RVF and Lane, GJ and Marsh, JC and Matters, DA and Polasik, M and Rzadkiewicz, J and Seweryniak, D and Zhu, S and Bottoni, S and Hayes, AB and Karamian, SA}, title = {Isomer depletion as experimental evidence of nuclear excitation by electron capture.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {216-218}, pmid = {29420479}, issn = {1476-4687}, abstract = {The atomic nucleus and its electrons are often thought of as independent systems that are held together in the atom by their mutual attraction. Their interaction, however, leads to other important effects, such as providing an additional decay mode for excited nuclear states, whereby the nucleus releases energy by ejecting an atomic electron instead of by emitting a γ-ray. This 'internal conversion' has been known for about a hundred years and can be used to study nuclei and their interaction with their electrons. In the inverse process-nuclear excitation by electron capture (NEEC)-a free electron is captured into an atomic vacancy and can excite the nucleus to a higher-energy state, provided that the kinetic energy of the free electron plus the magnitude of its binding energy once captured matches the nuclear energy difference between the two states. NEEC was predicted in 1976 and has not hitherto been observed. Here we report evidence of NEEC in molybdenum-93 and determine the probability and cross-section for the process in a beam-based experimental scenario. Our results provide a standard for the assessment of theoretical models relevant to NEEC, which predict cross-sections that span many orders of magnitude. The greatest practical effect of the NEEC process may be on the survival of nuclei in stellar environments, in which it could excite isomers (that is, long-lived nuclear states) to shorter-lived states. Such excitations may reduce the abundance of the isotope after its production. This is an example of 'isomer depletion', which has been investigated previously through other reactions, but is used here to obtain evidence for NEEC.}, } @article {pmid29420478, year = {2018}, author = {Kimsey, IJ and Szymanski, ES and Zahurancik, WJ and Shakya, A and Xue, Y and Chu, CC and Sathyamoorthy, B and Suo, Z and Al-Hashimi, HM}, title = {Dynamic basis for dG•dT misincorporation via tautomerization and ionization.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {195-201}, pmid = {29420478}, issn = {1476-4687}, support = {P01 GM066275/GM/NIGMS NIH HHS/United States ; P50 GM103297/GM/NIGMS NIH HHS/United States ; R01 GM089846/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anions ; *Base Pair Mismatch/genetics ; DNA/*biosynthesis/*chemistry/genetics ; *DNA Replication ; DNA-Directed DNA Polymerase/*metabolism ; Guanine/chemistry/*metabolism ; Humans ; Hydrogen-Ion Concentration ; Kinetics ; Magnetic Resonance Spectroscopy ; *Mutagenesis ; Probability ; Rats ; Thymine/chemistry/*metabolism ; }, abstract = {Tautomeric and anionic Watson-Crick-like mismatches have important roles in replication and translation errors through mechanisms that are not fully understood. Here, using NMR relaxation dispersion, we resolve a sequence-dependent kinetic network connecting G•T/U wobbles with three distinct Watson-Crick mismatches: two rapidly exchanging tautomeric species (Genol•T/UG•Tenol/Uenol; population less than 0.4%) and one anionic species (G•T-/U-; population around 0.001% at neutral pH). The sequence-dependent tautomerization or ionization step was inserted into a minimal kinetic mechanism for correct incorporation during replication after the initial binding of the nucleotide, leading to accurate predictions of the probability of dG•dT misincorporation across different polymerases and pH conditions and for a chemically modified nucleotide, and providing mechanisms for sequence-dependent misincorporation. Our results indicate that the energetic penalty for tautomerization and/or ionization accounts for an approximately 10-2 to 10-3-fold discrimination against misincorporation, which proceeds primarily via tautomeric dGenol•dT and dG•dTenol, with contributions from anionic dG•dT- dominant at pH 8.4 and above or for some mutagenic nucleotides.}, } @article {pmid29420477, year = {2018}, author = {Jewell, J and McCollum, D and Emmerling, J and Bertram, C and Gernaat, DEHJ and Krey, V and Paroussos, L and Berger, L and Fragkiadakis, K and Keppo, I and Saadi, N and Tavoni, M and van Vuuren, D and Vinichenko, V and Riahi, K}, title = {Limited emission reductions from fuel subsidy removal except in energy-exporting regions.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {229-233}, pmid = {29420477}, issn = {1476-4687}, mesh = {Carbon Dioxide/analysis ; Commerce/*economics/*statistics & numerical data ; Electricity ; Financing, Government/*economics/legislation & jurisprudence/*trends ; Fossil Fuels/*economics/*statistics & numerical data ; Global Warming/legislation & jurisprudence/*prevention & control ; Income/statistics & numerical data ; International Cooperation ; Poverty/economics/statistics & numerical data ; }, abstract = {Hopes are high that removing fossil fuel subsidies could help to mitigate climate change by discouraging inefficient energy consumption and levelling the playing field for renewable energy. In September 2016, the G20 countries re-affirmed their 2009 commitment (at the G20 Leaders' Summit) to phase out fossil fuel subsidies and many national governments are using today's low oil prices as an opportunity to do so. In practical terms, this means abandoning policies that decrease the price of fossil fuels and electricity generated from fossil fuels to below normal market prices. However, whether the removal of subsidies, even if implemented worldwide, would have a large impact on climate change mitigation has not been systematically explored. Here we show that removing fossil fuel subsidies would have an unexpectedly small impact on global energy demand and carbon dioxide emissions and would not increase renewable energy use by 2030. Subsidy removal would reduce the carbon price necessary to stabilize greenhouse gas concentration at 550 parts per million by only 2-12 per cent under low oil prices. Removing subsidies in most regions would deliver smaller emission reductions than the Paris Agreement (2015) climate pledges and in some regions global subsidy removal may actually lead to an increase in emissions, owing to either coal replacing subsidized oil and natural gas or natural-gas use shifting from subsidizing, energy-exporting regions to non-subsidizing, importing regions. Our results show that subsidy removal would result in the largest CO2 emission reductions in high-income oil- and gas-exporting regions, where the reductions would exceed the climate pledges of these regions and where subsidy removal would affect fewer people living below the poverty line than in lower-income regions.}, } @article {pmid29420476, year = {2018}, author = {Lu, LM and Mao, LF and Yang, T and Ye, JF and Liu, B and Li, HL and Sun, M and Miller, JT and Mathews, S and Hu, HH and Niu, YT and Peng, DX and Chen, YH and Smith, SA and Chen, M and Xiang, KL and Le, CT and Dang, VC and Lu, AM and Soltis, PS and Soltis, DE and Li, JH and Chen, ZD}, title = {Evolutionary history of the angiosperm flora of China.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {234-238}, pmid = {29420476}, issn = {1476-4687}, mesh = {*Biodiversity ; China ; Conservation of Natural Resources/methods ; Evolution, Molecular ; Geographic Mapping ; Magnoliopsida/*classification ; *Phylogeny ; Regression Analysis ; Spatio-Temporal Analysis ; }, abstract = {High species diversity may result from recent rapid speciation in a 'cradle' and/or the gradual accumulation and preservation of species over time in a 'museum'. China harbours nearly 10% of angiosperm species worldwide and has long been considered as both a museum, owing to the presence of many species with hypothesized ancient origins, and a cradle, as many lineages have originated as recent topographic changes and climatic shifts-such as the formation of the Qinghai-Tibetan Plateau and the development of the monsoon-provided new habitats that promoted remarkable radiation. However, no detailed phylogenetic study has addressed when and how the major components of the Chinese angiosperm flora assembled to form the present-day vegetation. Here we investigate the spatio-temporal divergence patterns of the Chinese flora using a dated phylogeny of 92% of the angiosperm genera for the region, a nearly complete species-level tree comprising 26,978 species and detailed spatial distribution data. We found that 66% of the angiosperm genera in China did not originate until early in the Miocene epoch (23 million years ago (Mya)). The flora of eastern China bears a signature of older divergence (mean divergence times of 22.04-25.39 Mya), phylogenetic overdispersion (spatial co-occurrence of distant relatives) and higher phylogenetic diversity. In western China, the flora shows more recent divergence (mean divergence times of 15.29-18.86 Mya), pronounced phylogenetic clustering (co-occurrence of close relatives) and lower phylogenetic diversity. Analyses of species-level phylogenetic diversity using simulated branch lengths yielded results similar to genus-level patterns. Our analyses indicate that eastern China represents a floristic museum, and western China an evolutionary cradle, for herbaceous genera; eastern China has served as both a museum and a cradle for woody genera. These results identify areas of high species richness and phylogenetic diversity, and provide a foundation on which to build conservation efforts in China.}, } @article {pmid29420475, year = {2018}, author = {Holen, SR and Deméré, TA and Fisher, DC and Fullagar, R and Paces, JB and Jefferson, GT and Beeton, JM and Cerutti, RA and Rountrey, AN and Vescera, L and Holen, KA}, title = {Holen et al. reply.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {E3}, pmid = {29420475}, issn = {1476-4687}, } @article {pmid29420474, year = {2018}, author = {Osterwalder, M and Barozzi, I and Tissières, V and Fukuda-Yuzawa, Y and Mannion, BJ and Afzal, SY and Lee, EA and Zhu, Y and Plajzer-Frick, I and Pickle, CS and Kato, M and Garvin, TH and Pham, QT and Harrington, AN and Akiyama, JA and Afzal, V and Lopez-Rios, J and Dickel, DE and Visel, A and Pennacchio, LA}, title = {Enhancer redundancy provides phenotypic robustness in mammalian development.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {239-243}, pmid = {29420474}, issn = {1476-4687}, support = {R01 HG003988/HG/NHGRI NIH HHS/United States ; R24 HL123879/HL/NHLBI NIH HHS/United States ; U54 HG006997/HG/NHGRI NIH HHS/United States ; UM1 HL098166/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Brain/embryology ; Enhancer Elements, Genetic/*genetics ; Extremities/*embryology ; Female ; Gene Expression Regulation, Developmental/*genetics ; Genome ; Heart/embryology ; Limb Deformities, Congenital/embryology/genetics ; Male ; Mice ; *Phenotype ; Sequence Deletion ; Spatio-Temporal Analysis ; }, abstract = {Distant-acting tissue-specific enhancers, which regulate gene expression, vastly outnumber protein-coding genes in mammalian genomes, but the functional importance of this regulatory complexity remains unclear. Here we show that the pervasive presence of multiple enhancers with similar activities near the same gene confers phenotypic robustness to loss-of-function mutations in individual enhancers. We used genome editing to create 23 mouse deletion lines and inter-crosses, including both single and combinatorial enhancer deletions at seven distinct loci required for limb development. Unexpectedly, none of the ten deletions of individual enhancers caused noticeable changes in limb morphology. By contrast, the removal of pairs of limb enhancers near the same gene resulted in discernible phenotypes, indicating that enhancers function redundantly in establishing normal morphology. In a genetic background sensitized by reduced baseline expression of the target gene, even single enhancer deletions caused limb abnormalities, suggesting that functional redundancy is conferred by additive effects of enhancers on gene expression levels. A genome-wide analysis integrating epigenomic and transcriptomic data from 29 developmental mouse tissues revealed that mammalian genes are very commonly associated with multiple enhancers that have similar spatiotemporal activity. Systematic exploration of three representative developmental structures (limb, brain and heart) uncovered more than one thousand cases in which five or more enhancers with redundant activity patterns were found near the same gene. Together, our data indicate that enhancer redundancy is a remarkably widespread feature of mammalian genomes that provides an effective regulatory buffer to prevent deleterious phenotypic consequences upon the loss of individual enhancers.}, } @article {pmid29420473, year = {2018}, author = {Amari, T and Canou, A and Aly, JJ and Delyon, F and Alauzet, F}, title = {Magnetic cage and rope as the key for solar eruptions.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {211-215}, pmid = {29420473}, issn = {1476-4687}, abstract = {Solar flares are spectacular coronal events that release large amounts of energy. They are classified as either eruptive or confined, depending on whether they are associated with a coronal mass ejection. Two types of model have been developed to identify the mechanism that triggers confined flares, although it has hitherto not been possible to decide between them because the magnetic field at the origin of the flares could not be determined with the required accuracy. In the first type of model, the triggering is related to the topological complexity of the flaring structure, which implies the presence of magnetically singular surfaces. This picture is observationally supported by the fact that radiative emission occurs near these features in many flaring regions. The second type of model attributes a key role to the formation of a twisted flux rope, which becomes unstable. Its plausibility is supported by simulations, by interpretations of some observations and by laboratory experiments. Here we report modelling of a confined event that uses the measured photospheric magnetic field as input. We first use a static model to compute the slowly evolving magnetic state of the corona before the eruption, and then use a dynamical model to determine the evolution during the eruption itself. We find that a magnetic flux rope must be present throughout the entire event to match the field measurements. This rope evolves slowly before saturating and suddenly erupting. Its energy is insufficient to break through the overlying field, whose lines form a confining cage, but its twist is large enough to trigger a kink instability, leading to the confined flare, as previously suggested. Topology is not the main cause of the flare, but it traces out the locations of the X-ray emission. We show that a weaker magnetic cage would have produced a more energetic eruption with a coronal mass ejection, associated with a predicted energy upper bound for a given region.}, } @article {pmid29420472, year = {2018}, author = {Nakamura, A and Kaneko, N and Villemagne, VL and Kato, T and Doecke, J and Doré, V and Fowler, C and Li, QX and Martins, R and Rowe, C and Tomita, T and Matsuzaki, K and Ishii, K and Ishii, K and Arahata, Y and Iwamoto, S and Ito, K and Tanaka, K and Masters, CL and Yanagisawa, K}, title = {High performance plasma amyloid-β biomarkers for Alzheimer's disease.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {249-254}, pmid = {29420472}, issn = {1476-4687}, mesh = {Aged ; Alzheimer Disease/*blood/cerebrospinal fluid/*diagnosis/metabolism ; Amyloid beta-Peptides/*blood/cerebrospinal fluid/metabolism ; Amyloid beta-Protein Precursor/*blood/metabolism ; Australia ; Biomarkers/blood/cerebrospinal fluid/metabolism ; Brain/metabolism ; Case-Control Studies ; Cognitive Dysfunction/blood/metabolism ; Cost-Benefit Analysis ; Female ; Humans ; Immunoprecipitation ; Japan ; Male ; Mass Spectrometry ; Peptide Fragments/*blood/cerebrospinal fluid/metabolism ; Positron-Emission Tomography ; Reproducibility of Results ; }, abstract = {To facilitate clinical trials of disease-modifying therapies for Alzheimer's disease, which are expected to be most efficacious at the earliest and mildest stages of the disease, supportive biomarker information is necessary. The only validated methods for identifying amyloid-β deposition in the brain-the earliest pathological signature of Alzheimer's disease-are amyloid-β positron-emission tomography (PET) imaging or measurement of amyloid-β in cerebrospinal fluid. Therefore, a minimally invasive, cost-effective blood-based biomarker is desirable. Despite much effort, to our knowledge, no study has validated the clinical utility of blood-based amyloid-β markers. Here we demonstrate the measurement of high-performance plasma amyloid-β biomarkers by immunoprecipitation coupled with mass spectrometry. The ability of amyloid-β precursor protein (APP)669-711/amyloid-β (Aβ)1-42 and Aβ1-40/Aβ1-42 ratios, and their composites, to predict individual brain amyloid-β-positive or -negative status was determined by amyloid-β-PET imaging and tested using two independent data sets: a discovery data set (Japan, n = 121) and a validation data set (Australia, n = 252 including 111 individuals diagnosed using 11C-labelled Pittsburgh compound-B (PIB)-PET and 141 using other ligands). Both data sets included cognitively normal individuals, individuals with mild cognitive impairment and individuals with Alzheimer's disease. All test biomarkers showed high performance when predicting brain amyloid-β burden. In particular, the composite biomarker showed very high areas under the receiver operating characteristic curves (AUCs) in both data sets (discovery, 96.7%, n = 121 and validation, 94.1%, n = 111) with an accuracy approximately equal to 90% when using PIB-PET as a standard of truth. Furthermore, test biomarkers were correlated with amyloid-β-PET burden and levels of Aβ1-42 in cerebrospinal fluid. These results demonstrate the potential clinical utility of plasma biomarkers in predicting brain amyloid-β burden at an individual level. These plasma biomarkers also have cost-benefit and scalability advantages over current techniques, potentially enabling broader clinical access and efficient population screening.}, } @article {pmid29420471, year = {2018}, author = {Wang, Z and Wu, J and Yang, W and Bera, AK and Kamenskyi, D and Islam, ATMN and Xu, S and Law, JM and Lake, B and Wu, C and Loidl, A}, title = {Experimental observation of Bethe strings.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {219-223}, pmid = {29420471}, issn = {1476-4687}, abstract = {Almost a century ago, string states-complex bound states of magnetic excitations-were predicted to exist in one-dimensional quantum magnets. However, despite many theoretical studies, the experimental realization and identification of string states in a condensed-matter system have yet to be achieved. Here we use high-resolution terahertz spectroscopy to resolve string states in the antiferromagnetic Heisenberg-Ising chain SrCo2V2O8 in strong longitudinal magnetic fields. In the field-induced quantum-critical regime, we identify strings and fractional magnetic excitations that are accurately described by the Bethe ansatz. Close to quantum criticality, the string excitations govern the quantum spin dynamics, whereas the fractional excitations, which are dominant at low energies, reflect the antiferromagnetic quantum fluctuations. Today, Bethe's result is important not only in the field of quantum magnetism but also more broadly, including in the study of cold atoms and in string theory; hence, we anticipate that our work will shed light on the study of complex many-body systems in general.}, } @article {pmid29420470, year = {2018}, author = {Urnavicius, L and Lau, CK and Elshenawy, MM and Morales-Rios, E and Motz, C and Yildiz, A and Carter, AP}, title = {Cryo-EM shows how dynactin recruits two dyneins for faster movement.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {202-206}, pmid = {29420470}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; MC_UP_A025_1011//Medical Research Council/United Kingdom ; R01 GM094522/GM/NIGMS NIH HHS/United States ; }, mesh = {Adaptor Proteins, Vesicular Transport/metabolism ; Animals ; Biological Transport ; *Cryoelectron Microscopy ; Dynactin Complex/*metabolism/*ultrastructure ; Dyneins/*metabolism/*ultrastructure ; Humans ; Mice ; Microtubule-Associated Proteins/metabolism ; Microtubules/metabolism ; Models, Molecular ; *Movement ; Single Molecule Imaging ; Swine ; }, abstract = {Dynein and its cofactor dynactin form a highly processive microtubule motor in the presence of an activating adaptor, such as BICD2. Different adaptors link dynein and dynactin to distinct cargoes. Here we use electron microscopy and single-molecule studies to show that adaptors can recruit a second dynein to dynactin. Whereas BICD2 is biased towards recruiting a single dynein, the adaptors BICDR1 and HOOK3 predominantly recruit two dyneins. We find that the shift towards a double dynein complex increases both the force and speed of the microtubule motor. Our 3.5 Å resolution cryo-electron microscopy reconstruction of a dynein tail-dynactin-BICDR1 complex reveals how dynactin can act as a scaffold to coordinate two dyneins side-by-side. Our work provides a structural basis for understanding how diverse adaptors recruit different numbers of dyneins and regulate the motile properties of the dynein-dynactin transport machine.}, } @article {pmid29420469, year = {2018}, author = {da Silva, JA and Tecuapetla, F and Paixão, V and Costa, RM}, title = {Dopamine neuron activity before action initiation gates and invigorates future movements.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {244-248}, pmid = {29420469}, issn = {1476-4687}, mesh = {Animals ; Dopamine/metabolism ; Dopaminergic Neurons/*metabolism ; Male ; Mice ; Movement/*physiology ; Parkinson Disease/metabolism/pathology/physiopathology ; Probability ; Psychomotor Performance ; Reward ; Substantia Nigra/cytology/physiology ; }, abstract = {Deciding when and whether to move is critical for survival. Loss of dopamine neurons (DANs) of the substantia nigra pars compacta (SNc) in patients with Parkinson's disease causes deficits in movement initiation and slowness of movement. The role of DANs in self-paced movement has mostly been attributed to their tonic activity, whereas phasic changes in DAN activity have been linked to reward prediction. This model has recently been challenged by studies showing transient changes in DAN activity before or during self-paced movement initiation. Nevertheless, the necessity of this activity for spontaneous movement initiation has not been demonstrated, nor has its relation to initiation versus ongoing movement been described. Here we show that a large proportion of SNc DANs, which did not overlap with reward-responsive DANs, transiently increased their activity before self-paced movement initiation in mice. This activity was not action-specific, and was related to the vigour of future movements. Inhibition of DANs when mice were immobile reduced the probability and vigour of future movements. Conversely, brief activation of DANs when mice were immobile increased the probability and vigour of future movements. Manipulations of dopamine activity after movement initiation did not affect ongoing movements. Similar findings were observed for the initiation and execution of learned action sequences. These findings causally implicate DAN activity before movement initiation in the probability and vigour of future movements.}, } @article {pmid29420468, year = {2018}, author = {Ferraro, JV and Binetti, KM and Wiest, LA and Esker, D and Baker, LE and Forman, SL}, title = {Contesting early archaeology in California.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {E1-E2}, pmid = {29420468}, issn = {1476-4687}, } @article {pmid29420467, year = {2018}, author = {Hyman, DM and Piha-Paul, SA and Won, H and Rodon, J and Saura, C and Shapiro, GI and Juric, D and Quinn, DI and Moreno, V and Doger, B and Mayer, IA and Boni, V and Calvo, E and Loi, S and Lockhart, AC and Erinjeri, JP and Scaltriti, M and Ulaner, GA and Patel, J and Tang, J and Beer, H and Selcuklu, SD and Hanrahan, AJ and Bouvier, N and Melcer, M and Murali, R and Schram, AM and Smyth, LM and Jhaveri, K and Li, BT and Drilon, A and Harding, JJ and Iyer, G and Taylor, BS and Berger, MF and Cutler, RE and Xu, F and Butturini, A and Eli, LD and Mann, G and Farrell, C and Lalani, AS and Bryce, RP and Arteaga, CL and Meric-Bernstam, F and Baselga, J and Solit, DB}, title = {HER kinase inhibition in patients with HER2- and HER3-mutant cancers.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {189-194}, pmid = {29420467}, issn = {1476-4687}, support = {R01 CA080195/CA/NCI NIH HHS/United States ; P30 CA016672/CA/NCI NIH HHS/United States ; T32 CA009207/CA/NCI NIH HHS/United States ; U01 CA180964/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P50 CA098131/CA/NCI NIH HHS/United States ; P30 CA014089/CA/NCI NIH HHS/United States ; 1U01 CA180964/NH/NIH HHS/United States ; R01 CA80195/NH/NIH HHS/United States ; R01 CA204749/CA/NCI NIH HHS/United States ; UL1 TR000371/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Alleles ; Antineoplastic Agents/pharmacology/therapeutic use ; Cohort Studies ; Female ; Humans ; Male ; Middle Aged ; Molecular Targeted Therapy ; *Mutation ; Mutation, Missense ; Neoplasms/*drug therapy/enzymology/*genetics ; Protein Kinase Inhibitors/pharmacology/therapeutic use ; Quinolines/adverse effects/*pharmacology/*therapeutic use ; Receptor, ErbB-2/*antagonists & inhibitors/chemistry/genetics ; Receptor, ErbB-3/*antagonists & inhibitors/chemistry/genetics ; Treatment Outcome ; }, abstract = {Somatic mutations of ERBB2 and ERBB3 (which encode HER2 and HER3, respectively) are found in a wide range of cancers. Preclinical modelling suggests that a subset of these mutations lead to constitutive HER2 activation, but most remain biologically uncharacterized. Here we define the biological and therapeutic importance of known oncogenic HER2 and HER3 mutations and variants of unknown biological importance by conducting a multi-histology, genomically selected, 'basket' trial using the pan-HER kinase inhibitor neratinib (SUMMIT; clinicaltrials.gov identifier NCT01953926). Efficacy in HER2-mutant cancers varied as a function of both tumour type and mutant allele to a degree not predicted by preclinical models, with the greatest activity seen in breast, cervical and biliary cancers and with tumours that contain kinase domain missense mutations. This study demonstrates how a molecularly driven clinical trial can be used to refine our biological understanding of both characterized and new genomic alterations with potential broad applicability for advancing the paradigm of genome-driven oncology.}, } @article {pmid29420466, year = {2018}, author = {Song, J and Chen, C and Zhu, S and Zhu, M and Dai, J and Ray, U and Li, Y and Kuang, Y and Li, Y and Quispe, N and Yao, Y and Gong, A and Leiste, UH and Bruck, HA and Zhu, JY and Vellore, A and Li, H and Minus, ML and Jia, Z and Martini, A and Li, T and Hu, L}, title = {Processing bulk natural wood into a high-performance structural material.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {224-228}, pmid = {29420466}, issn = {1476-4687}, mesh = {Alloys/chemistry ; Cell Wall/chemistry ; Cellulose/chemistry ; Hot Temperature ; Lignin/chemistry/isolation & purification ; Metals/chemistry ; Molecular Weight ; Polysaccharides/chemistry/isolation & purification ; Sodium Hydroxide/chemistry ; Sulfites/chemistry ; Tensile Strength ; Wood/*chemistry/classification ; }, abstract = {Synthetic structural materials with exceptional mechanical performance suffer from either large weight and adverse environmental impact (for example, steels and alloys) or complex manufacturing processes and thus high cost (for example, polymer-based and biomimetic composites). Natural wood is a low-cost and abundant material and has been used for millennia as a structural material for building and furniture construction. However, the mechanical performance of natural wood (its strength and toughness) is unsatisfactory for many advanced engineering structures and applications. Pre-treatment with steam, heat, ammonia or cold rolling followed by densification has led to the enhanced mechanical performance of natural wood. However, the existing methods result in incomplete densification and lack dimensional stability, particularly in response to humid environments, and wood treated in these ways can expand and weaken. Here we report a simple and effective strategy to transform bulk natural wood directly into a high-performance structural material with a more than tenfold increase in strength, toughness and ballistic resistance and with greater dimensional stability. Our two-step process involves the partial removal of lignin and hemicellulose from the natural wood via a boiling process in an aqueous mixture of NaOH and Na2SO3 followed by hot-pressing, leading to the total collapse of cell walls and the complete densification of the natural wood with highly aligned cellulose nanofibres. This strategy is shown to be universally effective for various species of wood. Our processed wood has a specific strength higher than that of most structural metals and alloys, making it a low-cost, high-performance, lightweight alternative.}, } @article {pmid29420294, year = {2018}, author = {Nobeli, I}, title = {In praise of slow.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {602}, doi = {10.1126/science.359.6375.602}, pmid = {29420294}, issn = {1095-9203}, } @article {pmid29420293, year = {2018}, author = {Dejea, CM and Fathi, P and Craig, JM and Boleij, A and Taddese, R and Geis, AL and Wu, X and DeStefano Shields, CE and Hechenbleikner, EM and Huso, DL and Anders, RA and Giardiello, FM and Wick, EC and Wang, H and Wu, S and Pardoll, DM and Housseau, F and Sears, CL}, title = {Patients with familial adenomatous polyposis harbor colonic biofilms containing tumorigenic bacteria.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {592-597}, pmid = {29420293}, issn = {1095-9203}, support = {P50 CA062924/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; P30 DK089502/DK/NIDDK NIH HHS/United States ; R01 CA151393/CA/NCI NIH HHS/United States ; T32 CA126607/CA/NCI NIH HHS/United States ; K08 DK087856/DK/NIDDK NIH HHS/United States ; }, mesh = {Adenomatous Polyposis Coli/*microbiology/*pathology ; Animals ; Bacterial Toxins/genetics ; Bacteroides fragilis/genetics/isolation & purification/*pathogenicity ; *Biofilms ; *Carcinogenesis ; Colon/*microbiology/pathology ; Colonic Neoplasms/*microbiology/pathology ; DNA Damage ; Escherichia coli/genetics/isolation & purification/*pathogenicity ; Gastrointestinal Microbiome ; Humans ; Interleukin-17/*analysis ; Intestinal Mucosa/chemistry/microbiology/pathology ; Metalloendopeptidases/genetics/metabolism ; Mice ; Peptides/genetics/metabolism ; Polyketides ; Precancerous Conditions/microbiology ; }, abstract = {Individuals with sporadic colorectal cancer (CRC) frequently harbor abnormalities in the composition of the gut microbiome; however, the microbiota associated with precancerous lesions in hereditary CRC remains largely unknown. We studied colonic mucosa of patients with familial adenomatous polyposis (FAP), who develop benign precursor lesions (polyps) early in life. We identified patchy bacterial biofilms composed predominately of Escherichia coli and Bacteroides fragilis Genes for colibactin (clbB) and Bacteroides fragilis toxin (bft), encoding secreted oncotoxins, were highly enriched in FAP patients' colonic mucosa compared to healthy individuals. Tumor-prone mice cocolonized with E. coli (expressing colibactin), and enterotoxigenic B. fragilis showed increased interleukin-17 in the colon and DNA damage in colonic epithelium with faster tumor onset and greater mortality, compared to mice with either bacterial strain alone. These data suggest an unexpected link between early neoplasia of the colon and tumorigenic bacteria.}, } @article {pmid29420292, year = {2018}, author = {Zhang, D and Tu, S and Stubna, M and Wu, WS and Huang, WC and Weng, Z and Lee, HC}, title = {The piRNA targeting rules and the resistance to piRNA silencing in endogenous genes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {587-592}, pmid = {29420292}, issn = {1095-9203}, support = {K99 GM108866/GM/NIGMS NIH HHS/United States ; P01 HD078253/HD/NICHD NIH HHS/United States ; R00 GM108866/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; CDC2 Protein Kinase/genetics ; Caenorhabditis elegans/*genetics ; *Gene Silencing ; Gene Targeting/*methods ; Green Fluorescent Proteins/genetics ; RNA, Helminth/*genetics ; RNA, Small Interfering/*genetics ; Transgenes ; }, abstract = {Piwi-interacting RNAs (piRNAs) silence transposons to safeguard genome integrity in animals. However, the functions of the many piRNAs that do not map to transposons remain unknown. Here, we show that piRNA targeting in Caenorhabditis elegans can tolerate a few mismatches but prefer perfect pairing at the seed region. The broad targeting capacity of piRNAs underlies the germline silencing of transgenes in C. elegans Transgenes engineered to avoid piRNA recognition are stably expressed. Many endogenous germline-expressed genes also contain predicted piRNA targeting sites, and periodic An/Tn clusters (PATCs) are an intrinsic signal that provides resistance to piRNA silencing. Together, our study revealed the piRNA targeting rules and highlights a distinct strategy that C. elegans uses to distinguish endogenous from foreign nucleic acids.}, } @article {pmid29420291, year = {2018}, author = {Zhu, H and Yi, J and Li, MY and Xiao, J and Zhang, L and Yang, CW and Kaindl, RA and Li, LJ and Wang, Y and Zhang, X}, title = {Observation of chiral phonons.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {579-582}, doi = {10.1126/science.aar2711}, pmid = {29420291}, issn = {1095-9203}, abstract = {Chirality reveals symmetry breaking of the fundamental interaction of elementary particles. In condensed matter, for example, the chirality of electrons governs many unconventional transport phenomena such as the quantum Hall effect. Here we show that phonons can exhibit intrinsic chirality in monolayer tungsten diselenide. The broken inversion symmetry of the lattice lifts the degeneracy of clockwise and counterclockwise phonon modes at the corners of the Brillouin zone. We identified the phonons by the intervalley transfer of holes through hole-phonon interactions during the indirect infrared absorption, and we confirmed their chirality by the infrared circular dichroism arising from pseudoangular momentum conservation. The chiral phonons are important for electron-phonon coupling in solids, phonon-driven topological states, and energy-efficient information processing.}, } @article {pmid29420290, year = {2018}, author = {Rajasekaran, S and Okamoto, J and Mathey, L and Fechner, M and Thampy, V and Gu, GD and Cavalleri, A}, title = {Probing optically silent superfluid stripes in cuprates.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {575-579}, doi = {10.1126/science.aan3438}, pmid = {29420290}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Unconventional superconductivity in the cuprates coexists with other types of electronic order. However, some of these orders are invisible to most experimental probes because of their symmetry. For example, the possible existence of superfluid stripes is not easily validated with linear optics, because the stripe alignment causes interlayer superconducting tunneling to vanish on average. Here we show that this frustration is removed in the nonlinear optical response. A giant terahertz third harmonic, characteristic of nonlinear Josephson tunneling, is observed in La1.885Ba0.115CuO4 above the transition temperature Tc = 13 kelvin and up to the charge-ordering temperature Tco = 55 kelvin. We model these results by hypothesizing the presence of a pair density wave condensate, in which nonlinear mixing of optically silent tunneling modes drives large dipole-carrying supercurrents.}, } @article {pmid29420289, year = {2018}, author = {Setvin, M and Reticcioli, M and Poelzleitner, F and Hulva, J and Schmid, M and Boatner, LA and Franchini, C and Diebold, U}, title = {Polarity compensation mechanisms on the perovskite surface KTaO3(001).}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {572-575}, doi = {10.1126/science.aar2287}, pmid = {29420289}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The stacking of alternating charged planes in ionic crystals creates a diverging electrostatic energy-a "polar catastrophe"-that must be compensated at the surface. We used scanning probe microscopies and density functional theory to study compensation mechanisms at the perovskite potassium tantalate (KTaO3) (001) surface as increasing degrees of freedom were enabled. The as-cleaved surface in vacuum is frozen in place but immediately responds with an insulator-to-metal transition and possibly ferroelectric lattice distortions. Annealing in vacuum allows the formation of isolated oxygen vacancies, followed by a complete rearrangement of the top layers into an ordered pattern of KO and TaO2 stripes. The optimal solution is found after exposure to water vapor through the formation of a hydroxylated overlayer with ideal geometry and charge.}, } @article {pmid29420288, year = {2018}, author = {Pagano, AM and Durner, GM and Rode, KD and Atwood, TC and Atkinson, SN and Peacock, E and Costa, DP and Owen, MA and Williams, TM}, title = {High-energy, high-fat lifestyle challenges an Arctic apex predator, the polar bear.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {568-572}, doi = {10.1126/science.aan8677}, pmid = {29420288}, issn = {1095-9203}, mesh = {Animals ; Arctic Regions ; Body Weight ; Eating ; *Energy Metabolism ; Feeding Behavior ; Ice Cover ; Movement ; Seasons ; Ursidae/*metabolism ; }, abstract = {Regional declines in polar bear (Ursus maritimus) populations have been attributed to changing sea ice conditions, but with limited information on the causative mechanisms. By simultaneously measuring field metabolic rates, daily activity patterns, body condition, and foraging success of polar bears moving on the spring sea ice, we found that high metabolic rates (1.6 times greater than previously assumed) coupled with low intake of fat-rich marine mammal prey resulted in an energy deficit for more than half of the bears examined. Activity and movement on the sea ice strongly influenced metabolic demands. Consequently, increases in mobility resulting from ongoing and forecasted declines in and fragmentation of sea ice are likely to increase energy demands and may be an important factor explaining observed declines in body condition and survival.}, } @article {pmid29420287, year = {2018}, author = {Mall, A and Sobotta, J and Huber, C and Tschirner, C and Kowarschik, S and Bačnik, K and Mergelsberg, M and Boll, M and Hügler, M and Eisenreich, W and Berg, IA}, title = {Reversibility of citrate synthase allows autotrophic growth of a thermophilic bacterium.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {563-567}, doi = {10.1126/science.aao2410}, pmid = {29420287}, issn = {1095-9203}, mesh = {Acetyl Coenzyme A/metabolism ; Adenosine Triphosphate/metabolism ; *Autotrophic Processes ; *Carbon Cycle ; Carbon Dioxide/*metabolism ; Citrate (si)-Synthase/*metabolism ; Citric Acid/metabolism ; Deltaproteobacteria/*enzymology/*growth & development ; Oxaloacetic Acid/metabolism ; }, abstract = {Biological inorganic carbon fixation proceeds through a number of fundamentally different autotrophic pathways that are defined by specific key enzymatic reactions. Detection of the enzymatic genes in (meta)genomes is widely used to estimate the contribution of individual organisms or communities to primary production. Here we show that the sulfur-reducing anaerobic deltaproteobacterium Desulfurella acetivorans is capable of both acetate oxidation and autotrophic carbon fixation, with the tricarboxylic acid cycle operating either in the oxidative or reductive direction, respectively. Under autotrophic conditions, the enzyme citrate synthase cleaves citrate adenosine triphosphate independently into acetyl coenzyme A and oxaloacetate, a reaction that has been regarded as impossible under physiological conditions. Because this overlooked, energetically efficient carbon fixation pathway lacks key enzymes, it may function unnoticed in many organisms, making bioinformatical predictions difficult, if not impossible.}, } @article {pmid29420286, year = {2018}, author = {Nunoura, T and Chikaraishi, Y and Izaki, R and Suwa, T and Sato, T and Harada, T and Mori, K and Kato, Y and Miyazaki, M and Shimamura, S and Yanagawa, K and Shuto, A and Ohkouchi, N and Fujita, N and Takaki, Y and Atomi, H and Takai, K}, title = {A primordial and reversible TCA cycle in a facultatively chemolithoautotrophic thermophile.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {559-563}, doi = {10.1126/science.aao3407}, pmid = {29420286}, issn = {1095-9203}, mesh = {Bacteria/*metabolism ; *Carbon Cycle ; *Chemoautotrophic Growth ; *Citric Acid Cycle ; }, abstract = {Inorganic carbon fixation is essential to sustain life on Earth, and the reductive tricarboxylic acid (rTCA) cycle is one of the most ancient carbon fixation metabolisms. A combination of genomic, enzymatic, and metabolomic analyses of a deeply branching chemolithotrophic Thermosulfidibacter takaii ABI70S6T revealed a previously unknown reversible TCA cycle whose direction was controlled by the available carbon source(s). Under a chemolithoautotrophic condition, a rTCA cycle occurred with the reverse reaction of citrate synthase (CS) and not with the adenosine 5'-triphosphate-dependent citrate cleavage reactions that had been regarded as essential for the conventional rTCA cycle. Phylometabolic evaluation suggests that the TCA cycle with reversible CS may represent an ancestral mode of the rTCA cycle and raises the possibility of a facultatively chemolithomixotrophic origin of life.}, } @article {pmid29420285, year = {2018}, author = {Müller, O and Pawlowski, MS and Jerjen, H and Lelli, F}, title = {A whirling plane of satellite galaxies around Centaurus A challenges cold dark matter cosmology.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {534-537}, doi = {10.1126/science.aao1858}, pmid = {29420285}, issn = {1095-9203}, abstract = {The Milky Way and Andromeda galaxies are each surrounded by a thin plane of satellite dwarf galaxies that may be corotating. Cosmological simulations predict that most satellite galaxy systems are close to isotropic with random motions, so those two well-studied systems are often interpreted as rare statistical outliers. We test this assumption using the kinematics of satellite galaxies around the Centaurus A galaxy. Our statistical analysis reveals evidence for corotation in a narrow plane: Of the 16 Centaurus A satellites with kinematic data, 14 follow a coherent velocity pattern aligned with the long axis of their spatial distribution. In standard cosmological simulations, <0.5% of Centaurus A-like systems show such behavior. Corotating satellite systems may be common in the universe, challenging small-scale structure formation in the prevailing cosmological paradigm.}, } @article {pmid29420284, year = {2018}, author = {Hemingway, J}, title = {Response: Integrated approach to malaria control.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {529}, doi = {10.1126/science.aar8094}, pmid = {29420284}, issn = {1095-9203}, mesh = {Humans ; *Malaria ; *Mosquito Control ; }, } @article {pmid29420283, year = {2018}, author = {Koenraadt, CJM and Takken, W}, title = {Integrated approach to malaria control.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {528-529}, doi = {10.1126/science.aar7554}, pmid = {29420283}, issn = {1095-9203}, mesh = {Humans ; *Malaria ; *Mosquito Control ; }, } @article {pmid29420282, year = {2018}, author = {Grillet, ME and Villegas, L and Oletta, JF and Tami, A and Conn, JE}, title = {Malaria in Venezuela requires response.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {528}, doi = {10.1126/science.aar5440}, pmid = {29420282}, issn = {1095-9203}, mesh = {Humans ; Malaria/*epidemiology/*prevention & control ; Venezuela ; World Health Organization ; }, } @article {pmid29420281, year = {2018}, author = {Vörösmarty, CJ and Osuna, VR and Koehler, DA and Klop, P and Spengler, JD and Buonocore, JJ and Cak, AD and Tessler, ZD and Corsi, F and Green, PA and Sánchez, R}, title = {Scientifically assess impacts of sustainable investments.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {523-525}, doi = {10.1126/science.aao3895}, pmid = {29420281}, issn = {1095-9203}, } @article {pmid29420280, year = {2018}, author = {Lee, JH}, title = {Tracing single-cell histories.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {521-522}, pmid = {29420280}, issn = {1095-9203}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; R35 GM119772/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Mutation ; *Neurogenesis ; }, } @article {pmid29420279, year = {2018}, author = {Boylan-Kolchin, M}, title = {Galaxy motions cause trouble for cosmology.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {520-521}, doi = {10.1126/science.aar7375}, pmid = {29420279}, issn = {1095-9203}, } @article {pmid29420278, year = {2018}, author = {Ergeçen, E and Gedik, N}, title = {Lighting up superconducting stripes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {519}, doi = {10.1126/science.aar5254}, pmid = {29420278}, issn = {1095-9203}, } @article {pmid29420277, year = {2018}, author = {Ragsdale, SW}, title = {Stealth reactions driving carbon fixation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {517-518}, doi = {10.1126/science.aar6329}, pmid = {29420277}, issn = {1095-9203}, support = {R37 GM039451/GM/NIGMS NIH HHS/United States ; }, mesh = {*Bacterial Physiological Phenomena ; *Carbon Cycle ; }, } @article {pmid29420276, year = {2018}, author = {Kvistborg, P and Yewdell, JW}, title = {Enhancing responses to cancer immunotherapy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {516-517}, doi = {10.1126/science.aar6574}, pmid = {29420276}, issn = {1095-9203}, mesh = {Cancer Vaccines ; Humans ; *Immunotherapy ; *Neoplasms ; }, } @article {pmid29420275, year = {2018}, author = {Whiteman, JP}, title = {Out of balance in the Arctic.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {514-515}, doi = {10.1126/science.aar6723}, pmid = {29420275}, issn = {1095-9203}, mesh = {Arctic Regions ; Humans ; }, } @article {pmid29420274, year = {2018}, author = {Starr, D}, title = {Human nature, observed.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {510-513}, doi = {10.1126/science.359.6375.510}, pmid = {29420274}, issn = {1095-9203}, mesh = {*Human Development ; Humans ; New Zealand ; Psychology, Developmental/*trends ; }, } @article {pmid29420273, year = {2018}, author = {Fraser, B}, title = {Dams nudge Amazon's ecosystems off-kilter.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {508-509}, doi = {10.1126/science.359.6375.508}, pmid = {29420273}, issn = {1095-9203}, mesh = {Animals ; Brazil ; *Catfishes ; *Construction Industry ; Ecosystem ; *Extinction, Biological ; *Rivers ; }, } @article {pmid29420272, year = {2018}, author = {Normile, D}, title = {Accelerator boom hones China's engineering expertise.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {507-508}, doi = {10.1126/science.359.6375.507}, pmid = {29420272}, issn = {1095-9203}, } @article {pmid29420271, year = {2018}, author = {Kupferschmidt, K}, title = {Forever young? Naked mole rats may know the secret.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {506-507}, doi = {10.1126/science.359.6375.506}, pmid = {29420271}, issn = {1095-9203}, mesh = {Aging/*physiology ; Animals ; *Body Temperature ; Longevity/physiology ; Mole Rats/*physiology ; }, } @article {pmid29420270, year = {2018}, author = {Voosen, P}, title = {NASA seeks to revive lost probe that traced solar storms.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {505}, doi = {10.1126/science.359.6375.505}, pmid = {29420270}, issn = {1095-9203}, } @article {pmid29420269, year = {2018}, author = {Han, AP}, title = {Judge orders unmasking of anonymous peer reviewers.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {504-505}, doi = {10.1126/science.359.6375.504}, pmid = {29420269}, issn = {1095-9203}, } @article {pmid29420268, year = {2018}, author = {Bagla, P}, title = {India plans to land near moon's south pole.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {503-504}, doi = {10.1126/science.359.6375.503}, pmid = {29420268}, issn = {1095-9203}, } @article {pmid29420267, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {500-502}, doi = {10.1126/science.359.6375.500}, pmid = {29420267}, issn = {1095-9203}, } @article {pmid29420266, year = {2018}, author = {Hockfield, S}, title = {Our science, our society.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {499}, doi = {10.1126/science.aat0957}, pmid = {29420266}, issn = {1095-9203}, } @article {pmid29420265, year = {2018}, author = {Bonan, GB and Doney, SC}, title = {Climate, ecosystems, and planetary futures: The challenge to predict life in Earth system models.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {}, doi = {10.1126/science.aam8328}, pmid = {29420265}, issn = {1095-9203}, mesh = {*Climate Change ; *Earth (Planet) ; *Ecosystem ; *Life ; Models, Biological ; Oceans and Seas ; }, abstract = {Many global change stresses on terrestrial and marine ecosystems affect not only ecosystem services that are essential to humankind, but also the trajectory of future climate by altering energy and mass exchanges with the atmosphere. Earth system models, which simulate terrestrial and marine ecosystems and biogeochemical cycles, offer a common framework for ecological research related to climate processes; analyses of vulnerability, impacts, and adaptation; and climate change mitigation. They provide an opportunity to move beyond physical descriptors of atmospheric and oceanic states to societally relevant quantities such as wildfire risk, habitat loss, water availability, and crop, fishery, and timber yields. To achieve this, the science of climate prediction must be extended to a more multifaceted Earth system prediction that includes the biosphere and its resources.}, } @article {pmid29420263, year = {2018}, author = {Bandres, MA and Wittek, S and Harari, G and Parto, M and Ren, J and Segev, M and Christodoulides, DN and Khajavikhan, M}, title = {Topological insulator laser: Experiments.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {}, doi = {10.1126/science.aar4005}, pmid = {29420263}, issn = {1095-9203}, abstract = {Physical systems exhibiting topological invariants are naturally endowed with robustness against perturbations, as manifested in topological insulators-materials exhibiting robust electron transport, immune from scattering by defects and disorder. Recent years have witnessed intense efforts toward exploiting these phenomena in photonics. Here we demonstrate a nonmagnetic topological insulator laser system exhibiting topologically protected transport in the cavity. Its topological properties give rise to single-mode lasing, robustness against defects, and considerably higher slope efficiencies compared to the topologically trivial counterparts. We further exploit the properties of active topological platforms by assembling the system from S-chiral microresonators, enforcing predetermined unidirectional lasing without magnetic fields. This work paves the way toward active topological devices with exciting properties and functionalities.}, } @article {pmid29420262, year = {2018}, author = {Mohanan, V and Nakata, T and Desch, AN and Lévesque, C and Boroughs, A and Guzman, G and Cao, Z and Creasey, E and Yao, J and Boucher, G and Charron, G and Bhan, AK and Schenone, M and Carr, SA and Reinecker, HC and Daly, MJ and Rioux, JD and Lassen, KG and Xavier, RJ}, title = {C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1161-1166}, pmid = {29420262}, issn = {1095-9203}, support = {U19 AI109725/AI/NIAID NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 DK068181/DK/NIDDK NIH HHS/United States ; U01 DK062432/DK/NIDDK NIH HHS/United States ; R01 DK064869/DK/NIDDK NIH HHS/United States ; R01 AI113333/AI/NIAID NIH HHS/United States ; R01 DK091247/DK/NIDDK NIH HHS/United States ; }, mesh = {ADP-Ribosylation Factors/metabolism ; Adherens Junctions/*genetics ; Animals ; Caco-2 Cells ; Guanine Nucleotide Exchange Factors/*metabolism ; HEK293 Cells ; Humans ; Immunoprecipitation ; Inflammatory Bowel Diseases/*genetics ; Intestinal Mucosa/pathology ; Mice ; Mice, Mutant Strains ; Phosphoproteins/genetics/*metabolism ; Polymorphism, Genetic ; Proteolysis ; Risk ; Ubiquitination/genetics ; }, abstract = {Polymorphisms in C1orf106 are associated with increased risk of inflammatory bowel disease (IBD). However, the function of C1orf106 and the consequences of disease-associated polymorphisms are unknown. Here we demonstrate that C1orf106 regulates adherens junction stability by regulating the degradation of cytohesin-1, a guanine nucleotide exchange factor that controls activation of ARF6. By limiting cytohesin-1-dependent ARF6 activation, C1orf106 stabilizes adherens junctions. Consistent with this model, C1orf106-/- mice exhibit defects in the intestinal epithelial cell barrier, a phenotype observed in IBD patients that confers increased susceptibility to intestinal pathogens. Furthermore, the IBD risk variant increases C1orf106 ubiquitination and turnover with consequent functional impairments. These findings delineate a mechanism by which a genetic polymorphism fine-tunes intestinal epithelial barrier integrity and elucidate a fundamental mechanism of cellular junctional control.}, } @article {pmid29420261, year = {2018}, author = {Vainchtein, ID and Chin, G and Cho, FS and Kelley, KW and Miller, JG and Chien, EC and Liddelow, SA and Nguyen, PT and Nakao-Inoue, H and Dorman, LC and Akil, O and Joshita, S and Barres, BA and Paz, JT and Molofsky, AB and Molofsky, AV}, title = {Astrocyte-derived interleukin-33 promotes microglial synapse engulfment and neural circuit development.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1269-1273}, pmid = {29420261}, issn = {1095-9203}, support = {R01 NS096369/NS/NINDS NIH HHS/United States ; T32 GM007618/GM/NIGMS NIH HHS/United States ; P30 NS065780/NS/NINDS NIH HHS/United States ; DP2 MH116507/MH/NIMH NIH HHS/United States ; K08 MH104417/MH/NIMH NIH HHS/United States ; K08 DK101604/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/*metabolism ; Central Nervous System/*growth & development/metabolism ; Homeostasis ; Interleukin-33/genetics/*metabolism ; Mice ; Mice, Knockout ; Microglia/*physiology ; Nerve Net/*growth & development ; *Neurogenesis ; Sensorimotor Cortex/growth & development/physiology ; Synapses/*physiology ; Thalamus/abnormalities ; }, abstract = {Neuronal synapse formation and remodeling are essential to central nervous system (CNS) development and are dysfunctional in neurodevelopmental diseases. Innate immune signals regulate tissue remodeling in the periphery, but how this affects CNS synapses is largely unknown. Here, we show that the interleukin-1 family cytokine interleukin-33 (IL-33) is produced by developing astrocytes and is developmentally required for normal synapse numbers and neural circuit function in the spinal cord and thalamus. We find that IL-33 signals primarily to microglia under physiologic conditions, that it promotes microglial synapse engulfment, and that it can drive microglial-dependent synapse depletion in vivo. These data reveal a cytokine-mediated mechanism required to maintain synapse homeostasis during CNS development.}, } @article {pmid29420260, year = {2018}, author = {Harari, G and Bandres, MA and Lumer, Y and Rechtsman, MC and Chong, YD and Khajavikhan, M and Christodoulides, DN and Segev, M}, title = {Topological insulator laser: Theory.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {}, doi = {10.1126/science.aar4003}, pmid = {29420260}, issn = {1095-9203}, abstract = {Topological insulators are phases of matter characterized by topological edge states that propagate in a unidirectional manner that is robust to imperfections and disorder. These attributes make topological insulator systems ideal candidates for enabling applications in quantum computation and spintronics. We propose a concept that exploits topological effects in a unique way: the topological insulator laser. These are lasers whose lasing mode exhibits topologically protected transport without magnetic fields. The underlying topological properties lead to a highly efficient laser, robust to defects and disorder, with single-mode lasing even at very high gain values. The topological insulator laser alters current understanding of the interplay between disorder and lasing, and at the same time opens exciting possibilities in topological physics, such as topologically protected transport in systems with gain. On the technological side, the topological insulator laser provides a route to arrays of semiconductor lasers that operate as one single-mode high-power laser coupled efficiently into an output port.}, } @article {pmid29420259, year = {2018}, author = {Hincks, T and Aspinall, W and Cooke, R and Gernon, T}, title = {Oklahoma's induced seismicity strongly linked to wastewater injection depth.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6381}, pages = {1251-1255}, doi = {10.1126/science.aap7911}, pmid = {29420259}, issn = {1095-9203}, abstract = {The sharp rise in Oklahoma seismicity since 2009 is due to wastewater injection. The role of injection depth is an open, complex issue, yet critical for hazard assessment and regulation. We developed an advanced Bayesian network to model joint conditional dependencies between spatial, operational, and seismicity parameters. We found that injection depth relative to crystalline basement most strongly correlates with seismic moment release. The joint effects of depth and volume are critical, as injection rate becomes more influential near the basement interface. Restricting injection depths to 200 to 500 meters above basement could reduce annual seismic moment release by a factor of 1.4 to 2.8. Our approach enables identification of subregions where targeted regulation may mitigate effects of induced earthquakes, aiding operators and regulators in wastewater disposal regions.}, } @article {pmid29420258, year = {2018}, author = {Nabhan, AN and Brownfield, DG and Harbury, PB and Krasnow, MA and Desai, TJ}, title = {Single-cell Wnt signaling niches maintain stemness of alveolar type 2 cells.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1118-1123}, pmid = {29420258}, issn = {1095-9203}, support = {R56 HL127471/HL/NHLBI NIH HHS/United States ; T32 GM007276/GM/NIGMS NIH HHS/United States ; U01 HL099995/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Cell Transdifferentiation ; Fibroblasts/cytology/metabolism ; Lung/physiology ; Lung Neoplasms/metabolism/pathology ; Mice ; Mice, Inbred C57BL ; Neoplastic Stem Cells/metabolism/pathology ; Pulmonary Alveoli/*cytology/metabolism ; Stem Cell Niche/*physiology ; Stem Cells/*cytology/metabolism ; *Wnt Signaling Pathway ; }, abstract = {Alveoli, the lung's respiratory units, are tiny sacs where oxygen enters the bloodstream. They are lined by flat alveolar type 1 (AT1) cells, which mediate gas exchange, and AT2 cells, which secrete surfactant. Rare AT2s also function as alveolar stem cells. We show that AT2 lung stem cells display active Wnt signaling, and many of them are near single, Wnt-expressing fibroblasts. Blocking Wnt secretion depletes these stem cells. Daughter cells leaving the Wnt niche transdifferentiate into AT1s: Maintaining Wnt signaling prevents transdifferentiation, whereas abrogating Wnt signaling promotes it. Injury induces AT2 autocrine Wnts, recruiting "bulk" AT2s as progenitors. Thus, individual AT2 stem cells reside in single-cell fibroblast niches providing juxtacrine Wnts that maintain them, whereas injury induces autocrine Wnts that transiently expand the progenitor pool. This simple niche maintains the gas exchange surface and is coopted in cancer.}, } @article {pmid29419405, year = {2018}, author = {Sweeney, HL and Hammers, DW}, title = {Muscle Contraction.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a023200}, pmid = {29419405}, issn = {1943-0264}, abstract = {Muscle cells are designed to generate force and movement. There are three types of mammalian muscles-skeletal, cardiac, and smooth. Skeletal muscles are attached to bones and move them relative to each other. Cardiac muscle comprises the heart, which pumps blood through the vasculature. Skeletal and cardiac muscles are known as striated muscles, because the filaments of actin and myosin that power their contraction are organized into repeating arrays, called sarcomeres, that have a striated microscopic appearance. Smooth muscle does not contain sarcomeres but uses the contraction of filaments of actin and myosin to constrict blood vessels and move the contents of hollow organs in the body. Here, we review the principal molecular organization of the three types of muscle and their contractile regulation through signaling mechanisms and discuss their major structural and functional similarities that hint at the possible evolutionary relationships between the cell types.}, } @article {pmid29418035, year = {2018}, author = {Cyriac, VP and Kodandaramaiah, U}, title = {Digging their own macroevolutionary grave: fossoriality as an evolutionary dead end in snakes.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {587-598}, doi = {10.1111/jeb.13248}, pmid = {29418035}, issn = {1420-9101}, abstract = {The tree of life is highly asymmetrical in its clade wise species richness, and this has often been attributed to variation in diversification rates either across time or lineages. Variations across lineages are usually associated with traits that increase lineage diversification. Certain traits can also hinder diversification by increasing extinction, and such traits are called evolutionary dead ends. Ecological specialization has usually been considered as an evolutionary dead end. However, recent analyses of specializations along single axes have provided mixed support for this model. Here, we test if fossoriality, a trait that forces specialization at multiple axes, acts as an evolutionary dead end in squamates (lizards and snakes) using recently developed phylogenetic comparative methods. We show that fossoriality is an evolutionary dead end in snakes but not in lizards. Fossorial snakes exhibit reduced speciation and increased extinction compared to nonfossorial snakes. Our analysis also indicates that transition rates from fossoriality to nonfossoriality in snakes are significantly lower than transition rates from nonfossoriality to fossoriality. Overall our results suggest that broad-scale ecological interactions that lead to specialization at multiple axes limit diversification.}, } @article {pmid29418031, year = {2018}, author = {Pahua, VJ and Stokes, PJN and Hollowell, AC and Regus, JU and Gano-Cohen, KA and Wendlandt, CE and Quides, KW and Lyu, JY and Sachs, JL}, title = {Fitness variation among host species and the paradox of ineffective rhizobia.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {599-610}, doi = {10.1111/jeb.13249}, pmid = {29418031}, issn = {1420-9101}, abstract = {Legumes can preferentially select beneficial rhizobial symbionts and sanction ineffective strains that fail to fix nitrogen. Yet paradoxically, rhizobial populations vary from highly beneficial to ineffective in natural and agricultural soils. Classic models of symbiosis focus on the single dimension of symbiont cost-benefit to sympatric hosts, but fail to explain the widespread persistence of ineffective rhizobia. Here, we test a novel framework predicting that spatio-temporal and community dynamics can maintain ineffective strains in rhizobial populations. We used clonal and multistrain inoculations and quantitative culturing to investigate the relative fitness of four focal Bradyrhizobium strains varying from effective to ineffective on Acmispon strigosus. We found that an ineffective Bradyrhizobium strain can be sanctioned by its native A. strigosus host across the host's range, forming fewer and smaller nodules compared to beneficial strains. But the same ineffective Bradyrhizobium strain exhibits a nearly opposite pattern on the broadly sympatric host Acmispon wrangelianus, forming large nodules in both clonal and multistrain inoculations. These data suggest that community-level effects could favour the persistence of ineffective rhizobia and contribute to variation in symbiotic nitrogen fixation.}, } @article {pmid29417719, year = {2018}, author = {Varela, SAM and Matos, M and Schlupp, I}, title = {The role of mate-choice copying in speciation and hybridization.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1304-1322}, doi = {10.1111/brv.12397}, pmid = {29417719}, issn = {1469-185X}, abstract = {Mate-choice copying, a social, non-genetic mechanism of mate choice, occurs when an individual (typically a female) copies the mate choice of other individuals via a process of social learning. Over the past 20 years, mate-choice copying has consistently been shown to affect mate choice in several species, by altering the genetically based expression of mating preferences. This behaviour has been claimed by several authors to have a significant role in evolution. Because it can cause or increase skews in male mating success, it seems to have the potential to induce a rapid change of the directionality and rate of sexual selection, possibly leading to divergent evolution and speciation. Theoretical work has, however, been challenging this view, showing that copying may decelerate sexual selection and that linkage disequilibrium cannot be established between the copied preference and the male trait, because females copy from unrelated individuals in the population, making an invasion of new and potentially fitter male traits difficult. Given this controversy, it is timely to ask about the real impact of mate-choice copying in speciation. We propose that a solution to this impasse may be the existence of some degree of habitat selection, which would create a spatial structure, causing scenarios of micro-allopatry and thus overcoming the problem of the lack of linkage disequilibrium. As far as we are aware, the potential role of mate-choice copying on fostering speciation in micro-allopatry has not been tackled. Also important is that the role of mate-choice copying has generally been discussed as being a barrier to gene flow. However, in our view, mate-choice copying may actually play a key role in facilitating gene flow, thereby fostering hybridization. Yet, the role of mate-choice copying in hybridization has so far been overlooked, although the conditions under which it might occur are more likely, or less restricted, than those favouring speciation. Hence, a conceptual framework is needed to identify the exact mechanisms and the conditions under which speciation or hybridization are expected. Here, we develop such a framework to be used as a roadmap for future research at the intersection of these research areas.}, } @article {pmid29417710, year = {2018}, author = {Cai, Q and Wang, JJ and Fu, B and Ying, SH and Feng, MG}, title = {Gcn5-dependent histone H3 acetylation and gene activity is required for the asexual development and virulence of Beauveria bassiana.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1484-1497}, doi = {10.1111/1462-2920.14066}, pmid = {29417710}, issn = {1462-2920}, abstract = {Gcn5 is a core histone acetyltransferase that catalyzes histone H3 acetylation on N-terminal lysine residues in yeasts and was reported to catalyze H3K9/K14 acetylation required for activating asexual development in Aspergillus. Here, we report a localization of Gcn5 ortholog in the nucleus and cytoplasm of Beauveria bassiana, a fungal insect pathogen. Deletion of gcn5 led to hypoacetylated H3 at K9/14/18/27 and 97% reduction in conidiation capacity as well as severe defects in colony growth and conidial thermotolerance. Two master conidiation genes, namely brlA and abaA, were transcriptionally repressed to undetectable level in Δgcn5, but sharply upregulated in wild-type, at the beginning time of conidiation. Based on chromatin immunoprecipitation, both DNA and acetylation levels of the distal and proximal fragments of the brlA promoter bound by acetylated H3K14 alone were upregulated in wild-type, but not in Δgcn5, at the mentioned time. In Δgcn5, normal cuticle infection was abolished while virulence through cuticle-bypassing infection was greatly attenuated, accompanied by drastically reduced activities of putative cuticle-degrading enzymes, retarded dimorphic transition and transcriptional repression of associated genes. These findings unveil a novel mechanism by which Gcn5 activates asexual development pathway by acetylating H3K14 and regulates the virulence-related cellular events in B. bassiana.}, } @article {pmid29417706, year = {2018}, author = {Heger, TJ and Giesbrecht, IJW and Gustavsen, J and Del Campo, J and Kellogg, CTE and Hoffman, KM and Lertzman, K and Mohn, WW and Keeling, PJ}, title = {High-throughput environmental sequencing reveals high diversity of litter and moss associated protist communities along a gradient of drainage and tree productivity.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1185-1203}, doi = {10.1111/1462-2920.14061}, pmid = {29417706}, issn = {1462-2920}, abstract = {Although previous studies, mostly based on microscopy analyses of a few groups of protists, have suggested that protists are abundant and diverse in litter and moss habitats, the overall diversity of moss and litter associated protists remains elusive. Here, high-throughput environmental sequencing was used to characterize the diversity and community structure of litter- and moss-associated protists along a gradient of soil drainage and forest primary productivity in a temperate rainforest in British Columbia. We identified 3262 distinct protist OTUs from 36 sites. Protists were strongly structured along the landscape gradient, with a significant increase in alpha diversity from the blanket bog ecosystem to the zonal forest ecosystem. Among all investigated environmental variables, calcium content was the most strongly associated with the community composition of protists, but substrate composition, plant cover and other edaphic factors were also significantly correlated with these communities. Furthermore, a detailed phylogenetic analysis of unicellular opisthokonts identified OTUs covering most lineages, including novel OTUs branching with Discicristoidea, the sister group of Fungi, and with Filasterea, one of the closest unicellular relatives to animals. Altogether, this study provides unprecedented insight into the community composition of moss- and litter-associated protists.}, } @article {pmid29417203, year = {2018}, author = {Zhang, Y and Xia, L and Lin, L and Tang, H and Osei-Adjei, G and Xu, S and Zhang, Y and Huang, X}, title = {Reciprocal Regulation of OmpR and Hfq and Their Regulatory Actions on the Vi Polysaccharide Capsular Antigen in Salmonella enterica Serovar Typhi.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {773-778}, pmid = {29417203}, issn = {1432-0991}, support = {31400125//National Natural Science Foundation of China/ ; 13JDG026//Professional Research Foundation for Advanced Talents of Jiangsu University/ ; 14KJB180005//Natural Science Fund for Colleges and Universities in Jiangsu Province/ ; }, mesh = {Bacterial Proteins/immunology/*metabolism ; Polysaccharides, Bacterial/*metabolism ; Salmonella typhi/immunology/*metabolism ; Virulence ; }, abstract = {Salmonella enterica serovar Typhi (S. Typhi) is the causative agent of human typhoid fever. S. Typhi expresses a major virulence determinant called Vi polysaccharide capsular antigen, which is encoded by the viaB locus containing 10 consecutive genes including tviA and tviB. Expression of Vi antigen is regulated by the two-component regulatory system EnvZ/OmpR and the global RNA-binding factor Hfq. In this study, we show that OmpR coordinates with Hfq to regulate the transcription of Vi antigen genes under osmotic stress conditions. OmpR binds to the promoters of tviA and its own genes to activate their transcription; however, it positively regulates tviB and negatively regulates hfq in an indirect manner. Moreover, Hfq reversely inhibits ompR, tviA and tviB, and positively regulates its own gene expression. Thus, we report of a complex gene regulatory network involving the reciprocal regulation and autoregulation of OmpR and Hfq, and their regulatory actions on Vi polysaccharide capsular antigen genes in S. Typhi.}, } @article {pmid29415769, year = {2018}, author = {Snodgrass, R and Nguyen, LT and Guo, M and Vaska, M and Naugler, C and Rashid-Kolvear, F}, title = {Incidence of acute lymphocytic leukemia in Calgary, Alberta, Canada: a retrospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {104}, pmid = {29415769}, issn = {1756-0500}, support = {RN254781-333204//Canadian Institutes of Health Research/Canada ; }, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Alberta/epidemiology ; Child ; Child, Preschool ; Female ; Humans ; Incidence ; Infant ; Male ; Middle Aged ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*epidemiology ; Retrospective Studies ; Young Adult ; }, abstract = {OBJECTIVE: Acute lymphocytic leukemia (ALL) is a rare malignant neoplasm that develops from abnormal lymphoid stem cells. ALL incidence is highest among children and declines towards adolescence. There is limited data on the epidemiology of ALL, especially in Canada. This retrospective cohort study used patient data from the Calgary Laboratory Services Cancer Cytogenetics Laboratory to report the incidence rate of ALL in Calgary, Alberta, Canada. New cases of ALL were identified for the 5-year period of January 1, 2011 until December 31, 2015. Reported incidence rates were categorized by sex and age groups, and age-standardized to the Canadian population.

RESULTS: There were an average of 11.4 new cases of ALL diagnosed per year between 2011 and 2015. The total incidence rate per 100,000 person-years was 0.84. Incidence rates peaked in children aged 0-4 with 7.55 and 3.32 cases per 100,000 person-years for males and females, respectively. The median age of diagnosis was 8 years. Incidence rates were generally lowest for adults aged 20 and over. The ratio of males to females diagnosed with ALL was 1.59. Overall, the recent incidence of ALL in Calgary is comparatively low with a preference for males and children below 5 years of age.}, } @article {pmid29415766, year = {2018}, author = {Ayele, A and Seyoum, Z and Leta, S}, title = {Cryptosporidium infection in bovine calves: prevalence and potential risk factors in northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {105}, pmid = {29415766}, issn = {1756-0500}, support = {(UoG-VPRCS/22/14)//University of Gondar/ ; }, mesh = {Animals ; Cattle ; Cattle Diseases/*epidemiology ; Cross-Sectional Studies ; Cryptosporidiosis/*epidemiology ; Cryptosporidium/*isolation & purification ; Ethiopia/epidemiology ; Female ; Male ; Prevalence ; Risk Factors ; }, abstract = {OBJECTIVE: Cryptosporidium is an enteric protozoan organism that causes gastrointestinal disorders in different animals, mainly in calves. The parasite has also a zoonotic importance of children and immunocompromised patients. However, data are limited to northwest Ethiopia. Therefore, we conducted a cross-sectional survey from October 2014 to April 2015 to estimate the prevalence of Cryptosporidium infection and to identify potential risk factors in bovine calves in northwest Ethiopia.

RESULTS: Out of the 360 examined calves, Cryptosporidium oocysts were recorded in 67 (18.6%) calves. Risk factors such as age, hygiene, faecal consistency, feed source, water source and contact with other domestic animals were significantly (P < 0.05) affected the occurrence of Cryptosporidium infection. However, significant variations (P > 0.05) were not recorded between Cryptosporidium infection and gender, body condition score, breed and study sites. Using multivariable analysis, age, feed source, water source, hygiene and close contact with other domestic animals were recognized as potential risk factors for the occurrence of Cryptosporidium infection. This study clearly figures out that Cryptosporidium infection is prevalent in the study area. Therefore, further studies, extension services and community education are recommended to adopt an integrated control approaches.}, } @article {pmid29415765, year = {2018}, author = {Ushijima, T and Kawaguchi, K and Matsumoto, T and Takagi, M and Kondoh, T and Nishimura, G and Iida, A and Ikegawa, S and Haga, N and Kato, G}, title = {Double non-contiguous fractures in a patient with spondylo-epiphyseal dysplasia with spinal ankylosis treated with open and percutaneous spinal fixation technique: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {106}, pmid = {29415765}, issn = {1756-0500}, mesh = {Female ; Fracture Fixation/*methods ; Humans ; Middle Aged ; Spinal Fractures/etiology/*surgery ; Spondylitis, Ankylosing/complications/*surgery ; }, abstract = {BACKGROUND: Patients with ankylosing spines are susceptible to developing spinal fractures even with minor trauma and can develop early or late neurological injuries. These fractures require early and aggressive surgical management to enable spinal stability and/or neural decompression. Being highly unstable by nature, they require relatively long segment instrumentation and fusion, which can increase paravertebral soft tissue damage and perioperative bleeding. The purpose of this report is to describe a rare case of traumatic double fractures at the cervico-thoracic and thoraco-lumbar transition zones in ankylosing spine with spondylo-epiphyseal dysplasia (SED) of unknown cause, which were successfully treated with a combined open and percutaneous spinal fusion procedure.

CASE PRESENTATION: A 46-year-old woman who was diagnosed with non-contiguous fractures in cervico-thoracic and thoraco-lumbar junction zones among multiple injuries sustained in a traffic accident was treated with hybrid techniques for posterior instrumentation with an open approach using a computed tomography (CT)-based navigation system and percutaneous pedicle-screwing method. She regained mobility to pre-admission levels and started walking on crutches 3 months postoperatively. Genetic testing for the cause of SED revealed no mutation in the COL2A1 or TRPVR4 genes. The union of fractured spine was confirmed on CT scan 1 year postoperatively.

CONCLUSION: This is the first report of double spinal fractures in an ankylosing spine with genetically undetermined spondyloepiphyseal dysplasia. A long-segment posterior instrumentation procedure incorporating the invasive treatment of spinal fractures in ankylosing spondylitis or diffuse idiopathic hyperostosis was effective.}, } @article {pmid29415764, year = {2018}, author = {Al-Farha, AA and Petrovski, K and Jozani, R and Hoare, A and Hemmatzadeh, F}, title = {Discrimination between some Mycoplasma spp. and Acholeplasma laidlawii in bovine milk using high resolution melting curve analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {107}, pmid = {29415764}, issn = {1756-0500}, mesh = {Acholeplasma laidlawii/*isolation & purification ; Animals ; Cattle ; Farms ; Female ; Mastitis, Bovine/diagnosis/*microbiology ; Milk/*microbiology ; Mycoplasma/*isolation & purification ; Mycoplasma bovis/isolation & purification ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*genetics ; South Australia ; }, abstract = {OBJECTIVES: This study aimed to provide a rapid, accurate and cost-effective diagnostic real time polymerase chain reaction-high resolution melting curve assay (PCR-HRM) to identify and distinguish between four different mycoplasmas and Acholeplasma laidlawii isolated at cow-level from a single commercial dairy farm in South Australia. One set of genus-level universal primers was designed targeting the 16S ribosomal RNA gene.

RESULTS: Real time PCR-HRM analysis was able to identify and distinguish between five different mollicutes, namely A. laidlawii, M. arginini, M. bovirhinis, M. bovis and uncultured Mycoplasma. Results were confirmed through sequencing. Our developed assay provides rapid and accurate screening for Mycoplasma mastitis detection.}, } @article {pmid29415761, year = {2018}, author = {Best, N and Gwozdz, J and Suter, R and Rawlin, G and Beddoe, T}, title = {Direct serogrouping of Dichelobacter nodosus from Victorian farms using conventional multiplex polymerase chain reaction.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {108}, pmid = {29415761}, issn = {1756-0500}, mesh = {Animals ; DNA, Bacterial/*genetics ; Dichelobacter nodosus/classification/*genetics ; Farms ; Fimbriae, Bacterial/*genetics ; Foot Rot/epidemiology/*microbiology ; Multiplex Polymerase Chain Reaction/*methods ; *Serogroup ; Serotyping/*methods ; Sheep ; Sheep Diseases/epidemiology/*microbiology ; Victoria/epidemiology ; }, abstract = {OBJECTIVE: Dichelobacter nodosus is the causative agent of footrot in sheep. Ovine footrot is a major problem in Australia that results in large economic losses and a represents a very significant animal welfare issue. D. nodosus is divided into 10 serogroups (A-I, M), based on sequence variation in the type IV fimbriae gene, fimA. Control of the bacteria is possible through use of serogroup-specific vaccination, however traditional identification of the serogroups of D. nodosus on infected sheep is time-consuming and costly. With the aim of reducing time and cost, a PCR assay was used to identify serogroups of D. nodosus directly from foot swabs of infected sheep in Victoria.

RESULTS: It was shown that serogroup B was most common (10 locations), followed by A, G and H (4 locations), I and C (2 locations), D, E and F (1 location). Infections with multiple serotypes were observed in 50% of farms, with the remaining 50% having only a single serogroup detected. The ability to identify serogroups quickly and cheaply direct from foot swabs will aid the understanding of the epidemiology of D. nodosus and support control programs.}, } @article {pmid29415713, year = {2018}, author = {Stanislas, T and Platre, MP and Liu, M and Rambaud-Lavigne, LES and Jaillais, Y and Hamant, O}, title = {A phosphoinositide map at the shoot apical meristem in Arabidopsis thaliana.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {20}, pmid = {29415713}, issn = {1741-7007}, abstract = {BACKGROUND: In plants, the shoot apical meristem (SAM) has two main functions, involving the production of all aerial organs on the one hand and self-maintenance on the other, allowing the production of organs during the entire post-embryonic life of the plant. Transcription factors, microRNA, hormones, peptides and forces have been involved in meristem function. Whereas phosphatidylinositol phosphates (PIPs) have been involved in almost all biological functions, including stem cell maintenance and organogenesis in animals, the processes in meristem biology to which PIPs contribute still need to be delineated.

RESULTS: Using biosensors for PI4P and PI(4,5)P2, the two most abundant PIPs at the plasma membrane, we reveal that meristem functions are associated with a stereotypical PIP tissue-scale pattern, with PI(4,5)P2 always displaying a more clear-cut pattern than PI4P. Using clavata3 and pin-formed1 mutants, we show that stem cell maintenance is associated with reduced levels of PIPs. In contrast, high PIP levels are signatures for organ-meristem boundaries. Interestingly, this pattern echoes that of cortical microtubules and stress anisotropy at the meristem. Using ablations and pharmacological approaches, we further show that PIP levels can be increased when the tensile stress pattern is altered. Conversely, we find that katanin mutant meristems, with increased isotropy of microtubule arrays and slower response to mechanical perturbations, exhibit reduced PIP gradients within the SAM. Comparable PIP pattern defects were observed in phospholipase A3β overexpressor lines, which largely phenocopy katanin mutants at the whole plant level.

CONCLUSIONS: Using phospholipid biosensors, we identified a stereotypical PIP accumulation pattern in the SAM that negatively correlates with stem cell maintenance and positively correlates with organ-boundary establishment. While other cues are very likely to contribute to the final PIP pattern, we provide evidence that the patterns of PIP, cortical microtubules and mechanical stress are positively correlated, suggesting that the PIP pattern, and its reproducibility, relies at least in part on the mechanical status of the SAM.}, } @article {pmid29415707, year = {2018}, author = {Paudel, PK and Sipos, J and Brodie, JF}, title = {Threatened species richness along a Himalayan elevational gradient: quantifying the influences of human population density, range size, and geometric constraints.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {6}, pmid = {29415707}, issn = {1472-6785}, support = {IRP201559//University of Ostrava/International ; }, abstract = {BACKGROUND: A crucial step in conserving biodiversity is to identify the distributions of threatened species and the factors associated with species threat status. In the biodiversity hotspot of the Himalaya, very little is known about which locations harbour the highest diversity of threatened species and whether diversity of such species is related to area, mid-domain effects (MDE), range size, or human density. In this study, we assessed the drivers of variation in richness of threatened birds, mammals, reptiles, actinopterygii, and amphibians along an elevational gradient in Nepal Himalaya.

RESULTS: Although geometric constraints (MDE), species range size, and human population density were significantly related to threatened species richness, the interaction between range size and human population density was of greater importance. Threatened species richness was positively associated with human population density and negatively associated with range size.

CONCLUSIONS: In areas with high richness of threatened species, species ranges tend to be small. The preponderance of species at risk of extinction at low elevations in the subtropical biodiversity hotspot could be due to the double impact of smaller range sizes and higher human density.}, } @article {pmid29415702, year = {2018}, author = {Chai, S and Tang, J and Mallik, A and Shi, Y and Zou, R and Li, J and Wei, X}, title = {Eco-physiological basis of shade adaptation of Camellia nitidissima, a rare and endangered forest understory plant of Southeast Asia.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {5}, pmid = {29415702}, issn = {1472-6785}, support = {31660092//National Natural Science Foundation of China (CN)/International ; 2015GXNSFBAA139089//Guangxi Natural Science Foundation Program/International ; 2016GXNSFBAA380122//Guangxi Natural Science Foundation Program/International ; Guike-AA17204056-1//Special Project on Innovation Driven Development of Guangxi/International ; }, abstract = {BACKGROUND: Camellia nitidissima, a rare and endangered shrub is narrowly distributed in South China and North Vietnam occurring in forest understory. Their light tolerance mechanism is unclear. We measured photosynthesis and related parameters on 2-years-old cuttings growing at 10, 30, 50 and 100% sunlight. Our research question was: At what light level are C. nitidissima cuttings responding most favorably, and what is the eco-physiological basis for their response to light? We hypothesized that as a forest understory growth of C. nitidissima would respond most favorably at low to intermediate light by optimizing photosynthetic activity, and high light will affect photosynthetic functions due to photoinhibition, damage of photosynthetic apparatus and concomitant enzyme activity.

RESULTS: With increasing light, the maximum net photosynthetic rate (PNmax) and apparent quantum yield (AQY) decreased, while the light compensation point increased, and light saturation point first increased followed by a decrease. The PNmax and AQY under 50 and 100% sunlight were significantly lower than that under 10 and 30% sunlight. The chlorophyll fluorescence parameters Fm, Fv, Fv/Fm all decreased under high light (> 50%). The contents of chlorophyll a (Chla), chlorophyll b (Chlb), and carotenoid (Car) decreased with increasing light. Relative conductivity, malondialdehyde (MDA) and proline contents in leaves were significantly increased in high light but we found no significant difference in these indices at 10 and 30% sunlight.

CONCLUSIONS: We conclude that C. nitidissima is a shade adapted plant with poor adaptability to high light (> 50%). The novelty of this research is the demonstration of the eco-physiological basis of its light tolerance (conversely, shade adaptation) mechanisms indicated by decreased photosynthetic activity, chlorophyll fluorescence, Chla, Chlb and Car contents and concomitant increase in relative conductivity, MDA and proline contents at high light causing photoinhibition. For artificial propagation of C. nitidissima we recommend growing cuttings below 30% sunlight. For in situ conservation of this valuable, rare and endangered shrub it is necessary to protect its natural habitats.}, } @article {pmid29415654, year = {2018}, author = {Zhou, J and Fu, BQ}, title = {The research on gene-disease association based on text-mining of PubMed.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {37}, pmid = {29415654}, issn = {1471-2105}, support = {2015A030308017//Natural Science Foundation of Guangdong Province/International ; }, mesh = {Algorithms ; *Data Mining ; Databases, Factual ; *Genetic Association Studies ; Genetic Predisposition to Disease ; Humans ; Medical Subject Headings ; *PubMed ; *Research ; }, abstract = {BACKGROUND: The associations between genes and diseases are of critical significance in aspects of prevention, diagnosis and treatment. Although gene-disease relationships have been investigated extensively, much of the underpinnings of these associations are yet to be elucidated.

METHODS: A novel method integrates MeSH database, term weight (TW), and co-occurrence methods to predict gene-disease associations based on the cosine similarity between gene vectors and disease vectors. Vectors are transformed from the texts of documents in the PubMed database according to the appearance and location of the gene or disease terms. The disease related text data has been optimized during the process of constructing vectors.

RESULTS: The overall distribution of cosine similarity value was investigated. By using the gene-disease association data in OMIM database as golden standard, the performance of cosine similarity in predicting gene-disease linkage was evaluated. The effects of applying weight matrix, penalty weights for keywords (PWK), and normalization were also investigated. Finally, we demonstrated that our method outperforms heterogeneous network edge prediction (HNEP) in aspects of precision rate and recall rate.

CONCLUSIONS: Our method proposed in this paper is easy to be conducted and the results can be integrated with other models to improve the overall performance of gene-disease association predictions.}, } @article {pmid29415652, year = {2018}, author = {Carvajal, F and Rosales, R and Palma, F and Manzano, S and Cañizares, J and Jamilena, M and Garrido, D}, title = {Transcriptomic changes in Cucurbita pepo fruit after cold storage: differential response between two cultivars contrasting in chilling sensitivity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {125}, pmid = {29415652}, issn = {1471-2164}, support = {AGL2014-54598-C2//Ministerio de Economía y Competitividad/International ; }, mesh = {Adaptation, Physiological ; *Cold Temperature ; Computational Biology/methods ; Cucurbita/*genetics/metabolism ; Energy Metabolism ; Fruit/*genetics ; Gene Expression Profiling ; Gene Expression Regulation, Plant ; Gene Ontology ; Molecular Sequence Annotation ; *Preservation, Biological/methods ; *Transcriptome ; }, abstract = {BACKGROUND: Zucchini fruit is susceptible to chilling injury (CI), but the response to low storage temperature is cultivar dependent. Previous reports about the response of zucchini fruit to chilling storage have been focused on the physiology and biochemistry of this process, with little information about the molecular mechanisms underlying it. In this work, we present a comprehensive analysis of transcriptomic changes that take place after cold storage in zucchini fruit of two commercial cultivars with contrasting response to chilling stress.

RESULTS: RNA-Seq analysis was conducted in exocarp of fruit at harvest and after 14 days of storage at 4 and 20 °C. Differential expressed genes (DEGs) were obtained comparing fruit stored at 4 °C with their control at 20 °C, and then specific and common up and down-regulated DEGs of each cultivar were identified. Functional analysis of these DEGs identified similarities between the response of zucchini fruit to low temperature and other stresses, with an important number of GO terms related to biotic and abiotic stresses overrepresented in both cultivars. This study also revealed several molecular mechanisms that could be related to chilling tolerance, since they were up-regulated in cv. Natura (CI tolerant) or down-regulated in cv. Sinatra (CI sensitive). These mechanisms were mainly those related to carbohydrate and energy metabolism, transcription, signal transduction, and protein transport and degradation. Among DEGs belonging to these pathways, we selected candidate genes that could regulate or promote chilling tolerance in zucchini fruit including the transcription factors MYB76-like, ZAT10-like, DELLA protein GAIP, and AP2/ERF domain-containing protein.

CONCLUSIONS: This study provides a broader understanding of the important mechanisms and processes related to coping with low temperature stress in zucchini fruit and allowed the identification of some candidate genes that may be involved in the acquisition of chilling tolerance in this crop. These genes will be the basis of future studies aimed to identify markers involved in cold tolerance and aid in zucchini breeding programs.}, } @article {pmid29415651, year = {2018}, author = {Oliveira, GB and Regitano, LCA and Cesar, ASM and Reecy, JM and Degaki, KY and Poleti, MD and Felício, AM and Koltes, JE and Coutinho, LL}, title = {Integrative analysis of microRNAs and mRNAs revealed regulation of composition and metabolism in Nelore cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {126}, pmid = {29415651}, issn = {1471-2164}, support = {2015/00617-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2015/24688-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 01/2005//Empresa Brasileira de Pesquisa Agropecuária/International ; }, mesh = {Animals ; Body Composition/*genetics ; Cattle ; Computational Biology/methods ; Energy Metabolism/*genetics ; *Gene Expression Regulation ; Gene Ontology ; Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; Phenotype ; *RNA Interference ; RNA, Messenger/*genetics ; Sequence Analysis, DNA ; Signal Transduction ; }, abstract = {BACKGROUND: The amount of intramuscular fat can influence the sensory characteristics and nutritional value of beef, thus the selection of animals with adequate fat deposition is important to the consumer. There is growing knowledge about the genes and pathways that control the biological processes involved in fat deposition in muscle. MicroRNAs (miRNAs) belong to a well-conserved class of non-coding small RNAs that modulate gene expression across a range of biological functions in animal development and physiology. The aim of this study was to identify differentially expressed (DE) miRNAs, regulatory candidate genes and co-expression networks related to intramuscular fat (IMF) deposition. To achieve this, we used mRNA and miRNA expression data from the Longissimus dorsi muscle of 30 Nelore steers with high (H) and low (L) genomic estimated breeding values (GEBV) for IMF deposition.

RESULTS: Differential miRNA expression analysis between animals with extreme GEBV values for IMF identified six DE miRNAs (FDR 10%). Functional annotation of the target genes for these microRNAs indicated that the PPARs signaling pathway is involved with IMF deposition. Candidate regulatory genes such as SDHAF4, FBXO17, ALDOA and PKM were identified by partial correlation with information theory (PCIT), phenotypic impact factor (PIF) and regulatory impact factor (RIF) co-expression approaches from integrated miRNA-mRNA expression data. Two DE miRNAs (FDR 10%), bta-miR-143 and bta-miR-146b, which were upregulated in the Low IMF group, were correlated with regulatory candidate genes, which were functionally enriched for fatty acid oxidation GO terms. Co-expression patterns obtained by weighted correlation network analysis (WGCNA), which showed possible interaction and regulation between mRNAs and miRNAs, identified several modules related to immune system function, protein metabolism, energy metabolism and glucose catabolism according to in silico analysis performed herein.

CONCLUSION: In this study, several genes and miRNAs were identified as candidate regulators of IMF by analyzing DE miRNAs using two different miRNA-mRNA co-expression network methods. This study contributes to the understanding of potential regulatory mechanisms of gene signaling networks involved in fat deposition processes measured in muscle. Glucose metabolism and inflammation processes were the main pathways found in silico to influence intramuscular fat deposition in beef cattle in the integrative mRNA-miRNA co-expression analysis.}, } @article {pmid29415650, year = {2018}, author = {Kondhare, KR and Kumar, A and Hannapel, DJ and Banerjee, AK}, title = {Conservation of polypyrimidine tract binding proteins and their putative target RNAs in several storage root crops.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {124}, pmid = {29415650}, issn = {1471-2164}, mesh = {Amino Acid Sequence ; Binding Sites ; Computational Biology/methods ; Conserved Sequence ; Crops, Agricultural/classification/*genetics/*metabolism ; Databases, Genetic ; Nucleotide Motifs ; Phylogeny ; Plant Proteins/chemistry/genetics/metabolism ; Polypyrimidine Tract-Binding Protein/chemistry/genetics/*metabolism ; Protein Binding ; RNA/chemistry/*genetics ; RNA, Messenger/chemistry/genetics/metabolism ; RNA, Plant/chemistry/genetics ; }, abstract = {BACKGROUND: Polypyrimidine-tract binding proteins (PTBs) are ubiquitous RNA-binding proteins in plants and animals that play diverse role in RNA metabolic processes. PTB proteins bind to target RNAs through motifs rich in cytosine/uracil residues to fine-tune transcript metabolism. Among tuber and root crops, potato has been widely studied to understand the mobile signals that activate tuber development. Potato PTBs, designated as StPTB1 and StPTB6, function in a long-distance transport system by binding to specific mRNAs (StBEL5 and POTH1) to stabilize them and facilitate their movement from leaf to stolon, the site of tuber induction, where they activate tuber and root growth. Storage tubers and root crops are important sustenance food crops grown throughout the world. Despite the availability of genome sequence for sweet potato, cassava, carrot and sugar beet, the molecular mechanism of root-derived storage organ development remains completely unexplored. Considering the pivotal role of PTBs and their target RNAs in potato storage organ development, we propose that a similar mechanism may be prevalent in storage root crops as well.

RESULTS: Through a bioinformatics survey utilizing available genome databases, we identify the orthologues of potato PTB proteins and two phloem-mobile RNAs, StBEL5 and POTH1, in five storage root crops - sweet potato, cassava, carrot, radish and sugar beet. Like potato, PTB1/6 type proteins from these storage root crops contain four conserved RNA Recognition Motifs (characteristic of RNA-binding PTBs) in their protein sequences. Further, 3´ UTR (untranslated region) analysis of BEL5 and POTH1 orthologues revealed the presence of several cytosine/uracil motifs, similar to those present in potato StBEL5 and POTH1 RNAs. Using RT-qPCR assays, we verified the presence of these related transcripts in leaf and root tissues of these five storage root crops. Similar to potato, BEL5-, PTB1/6- and POTH1-like orthologue RNAs from the aforementioned storage root crops exhibited differential accumulation patterns in leaf and storage root tissues.

CONCLUSIONS: Our results suggest that the PTB1/6-like orthologues and their putative targets, BEL5- and POTH1-like mRNAs, from storage root crops could interact physically, similar to that in potato, and potentially, could function as key molecular signals controlling storage organ development in root crops.}, } @article {pmid29415256, year = {2018}, author = {Senra, MVX and Sung, W and Ackerman, M and Miller, SF and Lynch, M and Soares, CAG}, title = {An Unbiased Genome-Wide View of the Mutation Rate and Spectrum of the Endosymbiotic Bacterium Teredinibacter turnerae.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {723-730}, pmid = {29415256}, issn = {1759-6653}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; }, mesh = {*Evolution, Molecular ; Gammaproteobacteria/*genetics ; Genetic Variation ; Genome, Bacterial ; Mutation ; Mutation Rate ; *Selection, Genetic ; Symbiosis/genetics ; }, abstract = {Mutations contribute to genetic variation in all living systems. Thus, precise estimates of mutation rates and spectra across a diversity of organisms are required for a full comprehension of evolution. Here, a mutation-accumulation (MA) assay was carried out on the endosymbiotic bacterium Teredinibacter turnerae. After ∼3,025 generations, base-pair substitutions (BPSs) and insertion-deletion (indel) events were characterized by whole-genome sequencing analysis of 47 independent MA lines, yielding a BPS rate of 1.14 × 10-9 per site per generation and indel rate of 1.55 × 10-10 events per site per generation, which are among the highest within free-living and facultative intracellular bacteria. As in other endosymbionts, a significant bias of BPSs toward A/T and an excess of deletion mutations over insertion mutations are observed for these MA lines. However, even with a deletion bias, the genome remains relatively large (∼5.2 Mb) for an endosymbiotic bacterium. The estimate of the effective population size (Ne) in T. turnerae is quite high and comparable to free-living bacteria (∼4.5 × 107), suggesting that the heavy bottlenecking associated with many endosymbiotic relationships is not prevalent during the life of this endosymbiont. The efficiency of selection scales with increasing Ne and such strong selection may have been operating against the deletion bias, preventing genome erosion. The observed mutation rate in this endosymbiont is of the same order of magnitude of those with similar Ne, consistent with the idea that population size is a primary determinant of mutation-rate evolution within endosymbionts, and that not all endosymbionts have low Ne.}, } @article {pmid29415174, year = {2018}, author = {Mutschlechner, M and Praeg, N and Illmer, P}, title = {The influence of cattle grazing on methane fluxes and engaged microbial communities in alpine forest soils.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {5}, pages = {}, doi = {10.1093/femsec/fiy019}, pmid = {29415174}, issn = {1574-6941}, abstract = {Recent dynamics and uncertainties in global methane budgets necessitate a dissemination of current knowledge on the controls of sources and sinks of atmospheric methane. Forest soils are considered to be efficient methane sinks; however, as they are microbially mediated they are sensitive to anthropogenic influences and tend to switch from being sinks to being methane sources. With regard to global changes in land use, the present study aimed at (i) investigating the influence of grazing on flux rates of methane in forest soils, (ii) deducing possible (a)biotic factors regulating these fluxes, and (iii) gaining an insight into the complex interactions between methane-cycling microorganisms and ecosystem functioning. Here we show that extensive grazing significantly mitigated the soil's sink strength for atmospheric methane through alterations of both microbial activity and community composition. In situ flux measurements revealed that all native, non-grazed areas were net methane consumers, while the adjacent, grazed areas were net methane producers. Whereas neither parent material nor soil properties including moisture and organic matter showed any correlation to the ascertained fluxes, significantly higher archaeal abundances at the grazed study sites indicated that small inputs of methanogens associated with cattle grazing may be sufficient to sustainably increase methane emissions.}, } @article {pmid29415151, year = {2018}, author = {Umanets, A and de Winter, I and IJdema, F and Ramiro-Garcia, J and van Hooft, P and Heitkönig, IMA and Prins, HHT and Smidt, H}, title = {Occupancy strongly influences faecal microbial composition of wild lemurs.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy017}, pmid = {29415151}, issn = {1574-6941}, abstract = {The microbiota of the mammalian gut is a complex ecosystem, the composition of which is greatly influenced by host genetics and environmental factors. In this study, we aim to investigate the influence of occupancy (a geographical area of habitation), species, age and sex on intestinal microbiota composition of the three lemur species: Eulemur fulvus, E. rubriventer and E. rufifrons. Faecal samples were collected from a total of 138 wild lemurs across Madagascar, and microbial composition was determined using next-generation sequencing of PCR-amplified 16S rRNA gene fragments. Consistent with reports from other primate species, the predominant phyla were Firmicutes (43 ± 6.4% [s.d.]) and Bacteroidetes (30.3 ± 5.3%). The microbial composition was strongly associated with occupancy in the E. fulvus population, with up to 19.9% of the total variation in microbial composition being explained by this factor. In turn, geographical differences observed in faecal microbiota of sympatric lemur species were less pronounced, as was the impact of the factors sex and age. Our findings showed that among the studied factors occupancy had the strongest influence on intestinal microbiota of congeneric lemur species. This suggests adaptation of microbiota to differences in forest composition, climate variations and correspondingly available diet in different geographical locations of Madagascar.}, } @article {pmid29414946, year = {2018}, author = {Knott, SRV and Wagenblast, E and Khan, S and Kim, SY and Soto, M and Wagner, M and Turgeon, MO and Fish, L and Erard, N and Gable, AL and Maceli, AR and Dickopf, S and Papachristou, EK and D'Santos, CS and Carey, LA and Wilkinson, JE and Harrell, JC and Perou, CM and Goodarzi, H and Poulogiannis, G and Hannon, GJ}, title = {Asparagine bioavailability governs metastasis in a model of breast cancer.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {378-381}, pmid = {29414946}, issn = {1476-4687}, support = {P30 ES010126/ES/NIEHS NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; P50 CA058223/CA/NCI NIH HHS/United States ; R00 CA194077/CA/NCI NIH HHS/United States ; P30 CA045508/CA/NCI NIH HHS/United States ; P01 CA013106/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Asparaginase/metabolism/therapeutic use ; Asparagine/deficiency/*metabolism ; Aspartate-Ammonia Ligase/genetics/metabolism ; Biological Availability ; Breast Neoplasms/enzymology/genetics/*metabolism/*pathology ; Cell Line, Tumor ; Disease Models, Animal ; Disease Progression ; Epithelial-Mesenchymal Transition/genetics ; Female ; Humans ; Lung Neoplasms/enzymology/metabolism/pathology/secondary ; Male ; Mice ; Neoplasm Invasiveness/pathology ; Neoplasm Metastasis/*pathology ; Prognosis ; Prostatic Neoplasms/enzymology/genetics/metabolism/pathology ; RNA Interference ; Reproducibility of Results ; }, abstract = {Using a functional model of breast cancer heterogeneity, we previously showed that clonal sub-populations proficient at generating circulating tumour cells were not all equally capable of forming metastases at secondary sites. A combination of differential expression and focused in vitro and in vivo RNA interference screens revealed candidate drivers of metastasis that discriminated metastatic clones. Among these, asparagine synthetase expression in a patient's primary tumour was most strongly correlated with later metastatic relapse. Here we show that asparagine bioavailability strongly influences metastatic potential. Limiting asparagine by knockdown of asparagine synthetase, treatment with l-asparaginase, or dietary asparagine restriction reduces metastasis without affecting growth of the primary tumour, whereas increased dietary asparagine or enforced asparagine synthetase expression promotes metastatic progression. Altering asparagine availability in vitro strongly influences invasive potential, which is correlated with an effect on proteins that promote the epithelial-to-mesenchymal transition. This provides at least one potential mechanism for how the bioavailability of a single amino acid could regulate metastatic progression.}, } @article {pmid29414945, year = {2018}, author = {Ashton, BJ and Ridley, AR and Edwards, EK and Thornton, A}, title = {Cognitive performance is linked to group size and affects fitness in Australian magpies.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {364-367}, pmid = {29414945}, issn = {1476-4687}, support = {BB/H021817/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Animals, Wild/physiology ; Australia ; *Biological Evolution ; Cognition/*physiology ; Female ; *Genetic Fitness ; Intelligence/physiology ; Male ; Passeriformes/*physiology ; Population Density ; Reproduction/physiology ; *Social Behavior ; }, abstract = {The social intelligence hypothesis states that the demands of social life drive cognitive evolution. This idea receives support from comparative studies that link variation in group size or mating systems with cognitive and neuroanatomical differences across species, but findings are contradictory and contentious. To understand the cognitive consequences of sociality, it is also important to investigate social variation within species. Here we show that in wild, cooperatively breeding Australian magpies, individuals that live in large groups show increased cognitive performance, which is linked to increased reproductive success. Individual performance was highly correlated across four cognitive tasks, indicating a 'general intelligence factor' that underlies cognitive performance. Repeated cognitive testing of juveniles at different ages showed that the correlation between group size and cognition emerged in early life, suggesting that living in larger groups promotes cognitive development. Furthermore, we found a positive association between the task performance of females and three indicators of reproductive success, thus identifying a selective benefit of greater cognitive performance. Together, these results provide intraspecific evidence that sociality can shape cognitive development and evolution.}, } @article {pmid29414944, year = {2018}, author = {Akrami, A and Kopec, CD and Diamond, ME and Brody, CD}, title = {Posterior parietal cortex represents sensory history and mediates its effects on behaviour.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {368-372}, pmid = {29414944}, issn = {1476-4687}, mesh = {Acoustic Stimulation ; Adult ; Animals ; Auditory Perception/*physiology ; Behavior/*physiology ; Behavior, Animal/physiology ; Female ; Humans ; Male ; Memory, Short-Term/*physiology ; Neurons/physiology ; Optogenetics ; Parietal Lobe/cytology/*physiology ; Psychometrics ; Rats ; Rats, Long-Evans ; Touch Perception/*physiology ; Young Adult ; }, abstract = {Many models of cognition and of neural computations posit the use and estimation of prior stimulus statistics: it has long been known that working memory and perception are strongly impacted by previous sensory experience, even when that sensory history is not relevant to the current task at hand. Nevertheless, the neural mechanisms and regions of the brain that are necessary for computing and using such prior experience are unknown. Here we report that the posterior parietal cortex (PPC) is a critical locus for the representation and use of prior stimulus information. We trained rats in an auditory parametric working memory task, and found that they displayed substantial and readily quantifiable behavioural effects of sensory-stimulus history, similar to those observed in humans and monkeys. Earlier proposals that the PPC supports working memory predict that optogenetic silencing of this region would impair behaviour in our working memory task. Contrary to this prediction, we found that silencing the PPC significantly improved performance. Quantitative analyses of behaviour revealed that this improvement was due to the selective reduction of the effects of prior sensory stimuli. Electrophysiological recordings showed that PPC neurons carried far more information about the sensory stimuli of previous trials than about the stimuli of the current trial. Furthermore, for a given rat, the more information about previous trial sensory history in the neural firing rates of the PPC, the greater the behavioural effect of sensory history, suggesting a tight link between behaviour and PPC representations of stimulus history. Our results indicate that the PPC is a central component in the processing of sensory-stimulus history, and could enable further neurobiological investigation of long-standing questions regarding how perception and working memory are affected by prior sensory information.}, } @article {pmid29414943, year = {2018}, author = {Wu, GA and Terol, J and Ibanez, V and López-García, A and Pérez-Román, E and Borredá, C and Domingo, C and Tadeo, FR and Carbonell-Caballero, J and Alonso, R and Curk, F and Du, D and Ollitrault, P and Roose, ML and Dopazo, J and Gmitter, FG and Rokhsar, DS and Talon, M}, title = {Genomics of the origin and evolution of Citrus.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {311-316}, pmid = {29414943}, issn = {1476-4687}, mesh = {Asia, Southeastern ; Biodiversity ; Citrus/*classification/*genetics ; Crop Production/history ; *Evolution, Molecular ; *Genetic Speciation ; Genome, Plant/*genetics ; *Genomics ; Haplotypes/genetics ; Heterozygote ; History, Ancient ; Human Migration ; Hybridization, Genetic ; *Phylogeny ; }, abstract = {The genus Citrus, comprising some of the most widely cultivated fruit crops worldwide, includes an uncertain number of species. Here we describe ten natural citrus species, using genomic, phylogenetic and biogeographic analyses of 60 accessions representing diverse citrus germ plasms, and propose that citrus diversified during the late Miocene epoch through a rapid southeast Asian radiation that correlates with a marked weakening of the monsoons. A second radiation enabled by migration across the Wallace line gave rise to the Australian limes in the early Pliocene epoch. Further identification and analyses of hybrids and admixed genomes provides insights into the genealogy of major commercial cultivars of citrus. Among mandarins and sweet orange, we find an extensive network of relatedness that illuminates the domestication of these groups. Widespread pummelo admixture among these mandarins and its correlation with fruit size and acidity suggests a plausible role of pummelo introgression in the selection of palatable mandarins. This work provides a new evolutionary framework for the genus Citrus.}, } @article {pmid29414942, year = {2018}, author = {He, L and Si, G and Huang, J and Samuel, ADT and Perrimon, N}, title = {Mechanical regulation of stem-cell differentiation by the stretch-activated Piezo channel.}, journal = {Nature}, volume = {555}, number = {7694}, pages = {103-106}, pmid = {29414942}, issn = {1476-4687}, support = {//Howard Hughes Medical Institute/United States ; R21 DA039582/DA/NIDA NIH HHS/United States ; P01 GM103770/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Calcium/metabolism ; Calcium Signaling ; *Cell Differentiation ; Cell Lineage ; Cell Proliferation ; Cytosol/metabolism ; Digestive System/cytology/metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/*cytology/*metabolism ; Enteroendocrine Cells/cytology/metabolism ; Female ; Ion Channels/genetics/*metabolism ; Mutation ; Stem Cells/*cytology ; *Stress, Mechanical ; }, abstract = {Somatic stem cells constantly adjust their self-renewal and lineage commitment by integrating various environmental cues to maintain tissue homeostasis. Although numerous chemical and biological signals have been identified that regulate stem-cell behaviour, whether stem cells can directly sense mechanical signals in vivo remains unclear. Here we show that mechanical stress regulates stem-cell differentiation in the adult Drosophila midgut through the stretch-activated ion channel Piezo. We find that Piezo is specifically expressed in previously unidentified enteroendocrine precursor cells, which have reduced proliferation ability and are destined to become enteroendocrine cells. Loss of Piezo activity reduces the generation of enteroendocrine cells in the adult midgut. In addition, ectopic expression of Piezo in all stem cells triggers both cell proliferation and enteroendocrine cell differentiation. Both the Piezo mutant and overexpression phenotypes can be rescued by manipulation of cytosolic Ca2+ levels, and increases in cytosolic Ca2+ resemble the Piezo overexpression phenotype, suggesting that Piezo functions through Ca2+ signalling. Further studies suggest that Ca2+ signalling promotes stem-cell proliferation and differentiation through separate pathways. Finally, Piezo is required for both mechanical activation of stem cells in a gut expansion assay and the increase of cytosolic Ca2+ in response to direct mechanical stimulus in a gut compression assay. Thus, our study demonstrates the existence of a specific group of stem cells in the fly midgut that can directly sense mechanical signals through Piezo.}, } @article {pmid29414941, year = {2018}, author = {Zhang, ZM and Lu, R and Wang, P and Yu, Y and Chen, D and Gao, L and Liu, S and Ji, D and Rothbart, SB and Wang, Y and Wang, GG and Song, J}, title = {Structural basis for DNMT3A-mediated de novo DNA methylation.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {387-391}, pmid = {29414941}, issn = {1476-4687}, support = {R01 CA218600/CA/NCI NIH HHS/United States ; R01 CA215284/CA/NCI NIH HHS/United States ; R01 CA211336/CA/NCI NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; S10 OD021832/OD/NIH HHS/United States ; 5R21ES025392/NH/NIH HHS/United States ; R21 ES025392/ES/NIEHS NIH HHS/United States ; R35 GM119721/GM/NIGMS NIH HHS/United States ; R35 GM124736/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Cell Proliferation ; CpG Islands/genetics ; Crystallography, X-Ray ; DNA/*chemistry/genetics/*metabolism ; DNA (Cytosine-5-)-Methyltransferases/*chemistry/genetics/*metabolism ; *DNA Methylation/genetics ; DNA-Binding Proteins/chemistry/genetics/metabolism ; Hematologic Neoplasms/enzymology/genetics/pathology ; Humans ; Models, Molecular ; Mutation ; Protein Binding ; Protein Domains ; Structure-Activity Relationship ; Substrate Specificity ; }, abstract = {DNA methylation by de novo DNA methyltransferases 3A (DNMT3A) and 3B (DNMT3B) at cytosines is essential for genome regulation and development. Dysregulation of this process is implicated in various diseases, notably cancer. However, the mechanisms underlying DNMT3 substrate recognition and enzymatic specificity remain elusive. Here we report a 2.65-ångström crystal structure of the DNMT3A-DNMT3L-DNA complex in which two DNMT3A monomers simultaneously attack two cytosine-phosphate-guanine (CpG) dinucleotides, with the target sites separated by 14 base pairs within the same DNA duplex. The DNMT3A-DNA interaction involves a target recognition domain, a catalytic loop, and DNMT3A homodimeric interface. Arg836 of the target recognition domain makes crucial contacts with CpG, ensuring DNMT3A enzymatic preference towards CpG sites in cells. Haematological cancer-associated somatic mutations of the substrate-binding residues decrease DNMT3A activity, induce CpG hypomethylation, and promote transformation of haematopoietic cells. Together, our study reveals the mechanistic basis for DNMT3A-mediated DNA methylation and establishes its aetiological link to human disease.}, } @article {pmid29414940, year = {2018}, author = {Ushio, M and Hsieh, CH and Masuda, R and Deyle, ER and Ye, H and Chang, CW and Sugihara, G and Kondoh, M}, title = {Fluctuating interaction network and time-varying stability of a natural fish community.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {360-363}, pmid = {29414940}, issn = {1476-4687}, mesh = {Animals ; Biodiversity ; *Ecosystem ; Fishes/classification/*physiology ; Japan ; Linear Models ; Population Dynamics ; Predatory Behavior ; Seasons ; Time Factors ; }, abstract = {Ecological theory suggests that large-scale patterns such as community stability can be influenced by changes in interspecific interactions that arise from the behavioural and/or physiological responses of individual species varying over time. Although this theory has experimental support, evidence from natural ecosystems is lacking owing to the challenges of tracking rapid changes in interspecific interactions (known to occur on timescales much shorter than a generation time) and then identifying the effect of such changes on large-scale community dynamics. Here, using tools for analysing nonlinear time series and a 12-year-long dataset of fortnightly collected observations on a natural marine fish community in Maizuru Bay, Japan, we show that short-term changes in interaction networks influence overall community dynamics. Among the 15 dominant species, we identify 14 interspecific interactions to construct a dynamic interaction network. We show that the strengths, and even types, of interactions change with time; we also develop a time-varying stability measure based on local Lyapunov stability for attractor dynamics in non-equilibrium nonlinear systems. We use this dynamic stability measure to examine the link between the time-varying interaction network and community stability. We find seasonal patterns in dynamic stability for this fish community that broadly support expectations of current ecological theory. Specifically, the dominance of weak interactions and higher species diversity during summer months are associated with higher dynamic stability and smaller population fluctuations. We suggest that interspecific interactions, community network structure and community stability are dynamic properties, and that linking fluctuating interaction networks to community-level dynamic properties is key to understanding the maintenance of ecological communities in nature.}, } @article {pmid29414939, year = {2018}, author = {Lopez, S and Tejos, N and Ledoux, C and Barrientos, LF and Sharon, K and Rigby, JR and Gladders, MD and Bayliss, MB and Pessa, I}, title = {A clumpy and anisotropic galaxy halo at redshift 1 from gravitational-arc tomography.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {493-496}, doi = {10.1038/nature25436}, pmid = {29414939}, issn = {1476-4687}, abstract = {Every star-forming galaxy has a halo of metal-enriched gas that extends out to at least 100 kiloparsecs, as revealed by the absorption lines that this gas imprints on the spectra of background quasars. However, quasars are sparse and typically probe only one narrow beam of emission through the intervening galaxy. Close quasar pairs and gravitationally lensed quasars have been used to circumvent this inherently one-dimensional technique, but these objects are rare and the structure of the circumgalactic medium remains poorly constrained. As a result, our understanding of the physical processes that drive the recycling of baryons across the lifetime of a galaxy is limited. Here we report integral-field (tomographic) spectroscopy of an extended background source-a bright, giant gravitational arc. We can thus coherently map the spatial and kinematic distribution of Mg ɪɪ absorption-a standard tracer of enriched gas-in an intervening galaxy system at redshift 0.98 (around 8 billion years ago). Our gravitational-arc tomography unveils a clumpy medium in which the absorption strength decreases with increasing distance from the galaxy system, in good agreement with results for quasars. Furthermore, we find strong evidence that the gas is not distributed isotropically. Interestingly, we detect little kinematic variation over a projected area of approximately 600 square kiloparsecs, with all line-of-sight velocities confined to within a few tens of kilometres per second of each other. These results suggest that the detected absorption originates from entrained recycled material, rather than in a galactic outflow.}, } @article {pmid29414938, year = {2018}, author = {Berns, DS and DeNardo, LA and Pederick, DT and Luo, L}, title = {Teneurin-3 controls topographic circuit assembly in the hippocampus.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {328-333}, pmid = {29414938}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 NS035050/NS/NINDS NIH HHS/United States ; F31 DC013240/DC/NIDCD NIH HHS/United States ; }, mesh = {Alternative Splicing ; Animals ; Axons/metabolism ; CA1 Region, Hippocampal/cytology/metabolism ; Cell Adhesion ; Drosophila melanogaster ; Entorhinal Cortex/metabolism ; Female ; Hippocampus/anatomy & histology/cytology/*metabolism ; Male ; Membrane Proteins/deficiency/genetics/*metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/deficiency/genetics/*metabolism ; *Neural Pathways ; Neurons/*metabolism ; Protein Binding ; }, abstract = {Brain functions rely on specific patterns of connectivity. Teneurins are evolutionarily conserved transmembrane proteins that instruct synaptic partner matching in Drosophila and are required for vertebrate visual system development. The roles of vertebrate teneurins in connectivity beyond the visual system remain largely unknown and their mechanisms of action have not been demonstrated. Here we show that mouse teneurin-3 is expressed in multiple topographically interconnected areas of the hippocampal region, including proximal CA1, distal subiculum, and medial entorhinal cortex. Viral-genetic analyses reveal that teneurin-3 is required in both CA1 and subicular neurons for the precise targeting of proximal CA1 axons to distal subiculum. Furthermore, teneurin-3 promotes homophilic adhesion in vitro in a splicing isoform-dependent manner. These findings demonstrate striking genetic heterogeneity across multiple hippocampal areas and suggest that teneurin-3 may orchestrate the assembly of a complex distributed circuit in the mammalian brain via matching expression and homophilic attraction.}, } @article {pmid29414937, year = {2018}, author = {Xu, M and Pokrovskii, M and Ding, Y and Yi, R and Au, C and Harrison, OJ and Galan, C and Belkaid, Y and Bonneau, R and Littman, DR}, title = {c-MAF-dependent regulatory T cells mediate immunological tolerance to a gut pathobiont.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {373-377}, pmid = {29414937}, issn = {1476-4687}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; S10 OD018338/OD/NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 DK103358/DK/NIDDK NIH HHS/United States ; S10 OD010584/OD/NIH HHS/United States ; T32 AI100853/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bioengineering ; Colitis/*immunology/*microbiology/pathology ; Female ; Forkhead Transcription Factors/metabolism ; Helicobacter hepaticus/genetics/*immunology/pathogenicity ; Homeostasis ; Host-Pathogen Interactions ; *Immune Tolerance ; Interleukin-10/biosynthesis/deficiency/immunology ; Intestines/*immunology/*microbiology ; Male ; Mice ; Nuclear Receptor Subfamily 1, Group F, Member 3/antagonists & inhibitors/metabolism ; Proto-Oncogene Proteins c-maf/deficiency/*metabolism ; T-Lymphocytes, Regulatory/cytology/*immunology/metabolism ; Th17 Cells/cytology/immunology ; }, abstract = {Both microbial and host genetic factors contribute to the pathogenesis of autoimmune diseases. There is accumulating evidence that microbial species that potentiate chronic inflammation, as in inflammatory bowel disease, often also colonize healthy individuals. These microorganisms, including the Helicobacter species, can induce pathogenic T cells and are collectively referred to as pathobionts. However, how such T cells are constrained in healthy individuals is not yet understood. Here we report that host tolerance to a potentially pathogenic bacterium, Helicobacter hepaticus, is mediated by the induction of RORγt+FOXP3+ regulatory T (iTreg) cells that selectively restrain pro-inflammatory T helper 17 (TH17) cells and whose function is dependent on the transcription factor c-MAF. Whereas colonization of wild-type mice by H. hepaticus promoted differentiation of RORγt-expressing microorganism-specific iTreg cells in the large intestine, in disease-susceptible IL-10-deficient mice, there was instead expansion of colitogenic TH17 cells. Inactivation of c-MAF in the Treg cell compartment impaired differentiation and function, including IL-10 production, of bacteria-specific iTreg cells, and resulted in the accumulation of H. hepaticus-specific inflammatory TH17 cells and spontaneous colitis. By contrast, RORγt inactivation in Treg cells had only a minor effect on the bacteria-specific Treg and TH17 cell balance, and did not result in inflammation. Our results suggest that pathobiont-dependent inflammatory bowel disease is driven by microbiota-reactive T cells that have escaped this c-MAF-dependent mechanism of iTreg-TH17 homeostasis.}, } @article {pmid29414828, year = {2018}, author = {Tafazzoli, K and Wünsch, L and Bouteleux, M and Lindert, J and Schulz, T and Birnbaum, W and Marshall, L and Hiort, O and Tüshaus, L}, title = {Endoscopy and Laparoscopy in Disorders of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {100-105}, doi = {10.1159/000486871}, pmid = {29414828}, issn = {1661-5433}, mesh = {Disorders of Sex Development/*diagnosis/diagnostic imaging ; Female ; Gonads/diagnostic imaging/pathology ; Humans ; *Laparoscopy ; Male ; }, abstract = {Endoscopy and laparoscopy are used for the assessment of disorders of sex development (DSD) and therapeutic interventions. Endoscopy (urethra-cystoscopy, vaginoscopy) is especially useful when vaginal or urethral surgery is planned. It is also valuable for the assessment of complications. Laparoscopy is used to identify sex ducts and gonads and to perform minimally invasive abdominal and pelvic surgery. This article reviews clinical indications, limitations, findings, and their reporting. It further discusses the impact of these findings on care in typical clinical situations.}, } @article {pmid29414445, year = {2018}, author = {Quatrini, R and Johnson, DB}, title = {Microbiomes in extremely acidic environments: functionalities and interactions that allow survival and growth of prokaryotes at low pH.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {139-147}, doi = {10.1016/j.mib.2018.01.011}, pmid = {29414445}, issn = {1879-0364}, mesh = {Acids/*pharmacology ; Archaea/genetics/*growth & development/physiology ; Hydrogen-Ion Concentration ; Metagenomics ; Microbial Consortia/drug effects/physiology ; Microbial Viability ; Microbiota/*drug effects/genetics/*physiology ; Phylogeny ; Proteobacteria/genetics/*growth & development/physiology ; }, abstract = {Extremely acidic environments have global distribution and can have natural or, increasingly, anthropogenic origins. Extreme acidophiles grow optimally at pH 3 or less, have multiple strategies for tolerating stresses that accompany high levels of acidity and are scattered in all three domains of the tree of life. Metagenomic studies have expanded knowledge of the diversity of extreme acidophile communities, their ecological networks and their metabolic potentials, both confirmed and inferred. High resolution compositional and functional profiling of these microbiomes have begun to reveal spatial diversity patterns at global, regional, local, zonal and micro-scales. Future integration of genomic and other meta-omic data will offer new opportunities to utilize acidic microbiomes and to engineer beneficial interactions within them in biotechnologies.}, } @article {pmid29414444, year = {2018}, author = {Howes, SC and Koning, RI and Koster, AJ}, title = {Correlative microscopy for structural microbiology.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {132-138}, doi = {10.1016/j.mib.2018.01.009}, pmid = {29414444}, issn = {1879-0364}, mesh = {Bacteria/ultrastructure ; Communicable Diseases/microbiology ; *Host Microbial Interactions ; Humans ; Mass Spectrometry ; Microscopy/instrumentation/*methods ; Microscopy, Electron/instrumentation/*methods ; Single Molecule Imaging/*instrumentation/methods ; Viruses/ultrastructure ; }, abstract = {Understanding how microbes utilize their environment is aided by visualizing them in their natural context at high resolution. Correlative imaging enables efficient targeting and identification of labelled viral and bacterial components by light microscopy combined with high resolution imaging by electron microscopy. Advances in genetic and bioorthogonal labelling, improved workflows for targeting and image correlation, and large-scale data collection are increasing the applicability of correlative imaging methods. Furthermore, developments in mass spectroscopy and soft X-ray imaging are expanding the correlative imaging modalities available. Investigating the structure and organization of microbes within their host by combined imaging methods provides important insights into mechanisms of infection and disease which cannot be obtained by other techniques.}, } @article {pmid29414443, year = {2018}, author = {Wierzchos, J and Casero, MC and Artieda, O and Ascaso, C}, title = {Endolithic microbial habitats as refuges for life in polyextreme environment of the Atacama Desert.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {124-131}, doi = {10.1016/j.mib.2018.01.003}, pmid = {29414443}, issn = {1879-0364}, mesh = {*Bacterial Physiological Phenomena ; Chile ; Desert Climate/*adverse effects ; *Ecosystem ; *Environmental Microbiology ; Heterotrophic Processes ; Microbial Consortia/physiology ; Phototrophic Processes ; Rain ; Ultraviolet Rays/adverse effects ; }, abstract = {The extremely harsh conditions of hyperarid deserts are a true challenge for microbial life. Microorganisms thriving in such polyextreme environments are fascinating as they can tell us more about life, its strategies and its boundaries than other groups of organisms. The Atacama Desert (North Chile) holds two world records of extreme environmental characteristics: the lowest rainfall and greatest surface ultraviolet radiation and total solar irradiance ever measured on Earth. Despite these limiting conditions for life, we recently identified several remarkable examples of endolithic habitats colonized by phototrophic and heterotrophic microorganisms in the hyperarid core of the Atacama Desert.}, } @article {pmid29414442, year = {2018}, author = {Lagree, K and Desai, JV and Finkel, JS and Lanni, F}, title = {Microscopy of fungal biofilms.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {100-107}, doi = {10.1016/j.mib.2017.12.008}, pmid = {29414442}, issn = {1879-0364}, support = {R01 AI067703/AI/NIAID NIH HHS/United States ; }, mesh = {*Biofilms ; Candida albicans/genetics/growth & development/physiology/*ultrastructure ; Fungi/growth & development/*physiology ; Gene Expression Regulation, Fungal ; Hyphae/genetics/ultrastructure ; Microscopy, Confocal/*methods ; }, abstract = {Fungal biofilms are heterogeneous, surface-associated colonies comprised of filamentous hyphae (chains of elongated cells), pseudohyphal cells, yeast-form cells, and various forms of extracellular matrix. When grown on a substratum under liquid culture medium, the microbial fungus Candida albicans forms dense biofilms that range in thickness from 100 to 600μm. Apical hyphae in the medium and invasive hyphae in the substratum may add greatly to the thickness and complexity of the biofilm. Because of the heterogeneity of the structure, and the large refractive index differences between cell walls, cytoplasm, and medium, fungal biofilms appear optically opaque. For fixed specimens that can be transferred out of an aqueous medium, refractive index matching methods provide a high degree of clarification. Confocal scanning, 2-photon scanning, or selective-plane illumination microscopy then can be used to obtain high-quality image data spanning the full thickness of the biofilm. Using refractive index matching and confocal microscopy, we have imaged many interesting features within wild-type, mutant, and engineered biofilms, including cellular phenotypes that vary with position, the effect of growth conditions, and gene expression through reporter constructs. This approach greatly expands the range of microscopical studies, allowing researchers to observe and quantify specific phenomena within medically or industrially relevant forms of microbial growth.}, } @article {pmid29411878, year = {2018}, author = {Janzen, T and Nolte, AW and Traulsen, A}, title = {The breakdown of genomic ancestry blocks in hybrid lineages given a finite number of recombination sites.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {735-750}, pmid = {29411878}, issn = {1558-5646}, abstract = {When a lineage originates from hybridization genomic blocks of contiguous ancestry from different ancestors are fragmented through genetic recombination. The resulting blocks are delineated by so called junctions, which accumulate with every generation that passes. Modeling the accumulation of ancestry block junctions can elucidate processes and timeframes of genomic admixture. Previous models have not addressed ancestry block dynamics for chromosomes that consist of a finite number of recombination sites. However, genomic data typically consist of informative markers that are interspersed with fragments for which no ancestry information is available. Hence, repeated recombination events may occur between markers, effectively removing existing junctions. Here, we present an analytical treatment of the dynamics of the mean number of junctions over time, taking into account the number of recombination sites per chromosome, population size, genetic map length, and the frequency of the ancestral species in the founding hybrid swarm. We describe the expected number of junctions using equidistant molecular markers and estimate the number of junctions using random markers. This extended theory of junctions thus reflects properties of empirical data and can serve to study the genomic patterns following admixture.}, } @article {pmid29411546, year = {2018}, author = {Zinser, ER}, title = {Cross-protection from hydrogen peroxide by helper microbes: the impacts on the cyanobacterium Prochlorococcus and other beneficiaries in marine communities.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {399-411}, doi = {10.1111/1758-2229.12625}, pmid = {29411546}, issn = {1758-2229}, abstract = {Hydrogen peroxide (HOOH) is a reactive oxygen species, derived from molecular oxygen, that is capable of damaging microbial cells. Surprisingly, the HOOH defence systems of some aerobes in the oxygenated marine environments are critically depleted, relative to model aerobes. For instance, the gene encoding catalase is absent in the numerically dominant photosynthetic cyanobacterium, Prochlorococcus. Accordingly, Prochlorococcus is highly susceptible to HOOH when exposed as pure cultures. Pure cultures do not exist in the marine environment, however. Catalase-positive community members can remove HOOH from the seawater medium, thus lowering the threat to Prochlorococcus and any other member that likewise lacks their own catalase. This cross-protection may constitute a loosely defined symbiosis, whereby the catalase-positive helper cells may benefit through the acquisition of nutrients released by the beneficiaries such as Prochlorococcus. Other members of the community that may be helped by the catalase-positive cells may include some lineages of Synechococcus - the sister genus of Prochlorococcus - as well as some lineages of SAR11 and ammonia oxidizing archaea and bacteria. The co-occurrence of catalase-positive and -negative members suggests that cross-protection from HOOH-mediated oxidative stress may play an important role in the construction of the marine microbial community.}, } @article {pmid29411545, year = {2018}, author = {Zinser, ER}, title = {The microbial contribution to reactive oxygen species dynamics in marine ecosystems.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {412-427}, doi = {10.1111/1758-2229.12626}, pmid = {29411545}, issn = {1758-2229}, abstract = {This review surveys the current state of knowledge of the concentrations, sources and sinks of reactive oxygen species (ROS) in the ocean. Both abiotic and biotic factors contribute to ROS dynamics in seawater, and ROS can feature prominently in marine microbe-microbe interactions. The sun plays a key role in the production of ROS in the ocean, and consequently ROS concentrations are typically maximal in the sun-exposed surface. However, microbes can also contribute significantly to extracellular ROS. Production of superoxide is widespread within the microbial community, and may benefit the producers as antimicrobial agents or perhaps more generally, as a means of nutrient scavenging. Decomposition of hydrogen peroxide is a community-wide activity, though some members may play less significant roles in this process. The more reactive forms of ROS, singlet oxygen and the hydroxyl radical, may be less important as microbial stressors, as they tend to react with the chemicals in seawater before they can contact the cells. However, exceptions may exist for microbes attached to singlet oxygen-generating sinking particulate matter. Extracellular ROS thus plays an important role in the ecology of marine microbes, the full extent to which we are only beginning to appreciate.}, } @article {pmid29411544, year = {2018}, author = {Thompson, A and Fulde, M and Tedin, K}, title = {The metabolic pathways utilized by Salmonella Typhimurium during infection of host cells.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {140-154}, doi = {10.1111/1758-2229.12628}, pmid = {29411544}, issn = {1758-2229}, support = {BB/D004810/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F00978X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J001007/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Host-Pathogen Interactions ; Humans ; Metabolic Networks and Pathways ; Salmonella Infections/*microbiology ; Salmonella typhimurium/genetics/*metabolism/pathogenicity ; Virulence ; }, abstract = {Only relatively recently has research on the metabolism of intracellular bacterial pathogens within their host cells begun to appear in the published literature. This reflects in part the experimental difficulties encountered in separating host metabolic processes from those of the resident pathogen. One of the most genetically tractable and thoroughly studied intracellular bacterial pathogens, Salmonella enterica serovar Typhimurium (S. Typhimurium), has been at the forefront of metabolic studies within eukaryotic host cells. In this review, we offer a synthesis of what has been discovered to date regarding the metabolic adaptation of S. Typhimurium to survival and growth within the infected host. We discuss many studies in the context of techniques used, types of host cells, how host metabolites contribute to intracellular survival and proliferation of the pathogen and how bacterial metabolism affects the virulence and persistence of the pathogen.}, } @article {pmid29411533, year = {2018}, author = {Lindh, MV and Maillot, BM and Smith, CR and Church, MJ}, title = {Habitat filtering of bacterioplankton communities above polymetallic nodule fields and sediments in the Clarion-Clipperton zone of the Pacific Ocean.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {113-122}, doi = {10.1111/1758-2229.12627}, pmid = {29411533}, issn = {1758-2229}, mesh = {Bacteria/classification/genetics/*isolation & purification ; Biodiversity ; Ecosystem ; Geologic Sediments/analysis/*microbiology ; Pacific Ocean ; Phylogeny ; }, abstract = {Deep-sea mining of commercially valuable polymetallic nodule fields will generate a seabed sediment plume into the water column. Yet, the response of bacterioplankton communities, critical in regulating energy and matter fluxes in marine ecosystems, to such disturbances is unknown. Metacommunity theory, traditionally used in general ecology for macroorganisms, offers mechanistic understanding on the relative role of spatial differences compared with local environmental conditions (habitat filtering) for community assembly. We examined bacterioplankton metacommunities using 16S rRNA amplicons from the Clarion-Clipperton Zone (CCZ) in the eastern Pacific Ocean and in global ocean transect samples to determine sensitivity of these assemblages to environmental perturbations. Habitat filtering was the main assembly mechanism of bacterioplankton community composition in the epi- and mesopelagic waters of the CCZ and the Tara Oceans transect. Bathy- and abyssopelagic bacterioplankton assemblages were mainly assembled by undetermined metacommunity types or neutral and dispersal-driven patch-dynamics for the CCZ and the Malaspina transect. Environmental disturbances may alter the structure of upper-ocean microbial assemblages, with potentially even more substantial, yet unknown, impact on deep-sea communities. Predicting such responses in bacterioplankton assemblage dynamics can improve our understanding of microbially-mediated regulation of ecosystem services in the abyssal seabed likely to be exploited by future deep-sea mining operations.}, } @article {pmid29411516, year = {2018}, author = {Yao, J and Guo, Y and Wang, P and Zeng, Z and Li, B and Tang, K and Liu, X and Wang, X}, title = {Type II toxin/antitoxin system ParESO /CopASO stabilizes prophage CP4So in Shewanella oneidensis.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1224-1239}, doi = {10.1111/1462-2920.14068}, pmid = {29411516}, issn = {1462-2920}, abstract = {Toxin/antitoxin (TA) loci are commonly found in mobile genetic elements such as plasmids and prophages. However, the physiological functions of these TA loci in prophages and cross-regulation among these TA loci remain largely unexplored. Here, we characterized a newly discovered type II TA pair, ParESO /CopASO , in the CP4So prophage in Shewanella oneidensis. We demonstrated that ParESO /CopASO plays a critical role in the maintenance of CP4So in host cells after its excision. The toxin ParESO inhibited cell growth, resulting in filamentous growth and eventually cell death. The antitoxin CopASO neutralized the toxicity of ParESO through direct protein-protein interactions and repressed transcription of the TA operon by binding to a DNA motif in the promoter region containing two inverted repeats [5'-GTANTAC (N)3 GTANTAC-3']. CopASO also repressed transcription of another TA system PemKSO /PemISO in megaplasmid pMR-1 of S. oneidensis through binding to a highly similar DNA motif in its promoter region. CopASO homologs are widely spread in Shewanella and other Proteobacteria, either as a component of a TA pair or as orphan antitoxins. Our study thus illustrated the cross-regulation of the TA systems in different mobile genetic elements and expanded our understanding of the physiological function of TA systems.}, } @article {pmid29411510, year = {2018}, author = {Blum, JM and Su, Q and Ma, Y and Valverde-Pérez, B and Domingo-Félez, C and Jensen, MM and Smets, BF}, title = {The pH dependency of N-converting enzymatic processes, pathways and microbes: effect on net N2 O production.}, journal = {Environmental microbiology}, volume = {20}, number = {5}, pages = {1623-1640}, doi = {10.1111/1462-2920.14063}, pmid = {29411510}, issn = {1462-2920}, abstract = {Nitrous oxide (N2 O) is emitted during microbiological nitrogen (N) conversion processes, when N2 O production exceeds N2 O consumption. The magnitude of N2 O production vs. consumption varies with pH and controlling net N2 O production might be feasible by choice of system pH. This article reviews how pH affects enzymes, pathways and microorganisms that are involved in N-conversions in water engineering applications. At a molecular level, pH affects activity of cofactors and structural elements of relevant enzymes by protonation or deprotonation of amino acid residues or solvent ligands, thus causing steric changes in catalytic sites or proton/electron transfer routes that alter the enzymes' overall activity. Augmenting molecular information with, e.g., nitritation or denitrification rates yields explanations of changes in net N2 O production with pH. Ammonia oxidizing bacteria are of highest relevance for N2 O production, while heterotrophic denitrifiers are relevant for N2 O consumption at pH > 7.5. Net N2 O production in N-cycling water engineering systems is predicted to display a 'bell-shaped' curve in the range of pH 6.0-9.0 with a maximum at pH 7.0-7.5. Net N2 O production at acidic pH is dominated by N2 O production, whereas N2 O consumption can outweigh production at alkaline pH. Thus, pH 8.0 may be a favourable pH set-point for water treatment applications regarding net N2 O production.}, } @article {pmid29411502, year = {2018}, author = {Lv, H and Sahin, N and Tani, A}, title = {Isolation and genomic characterization of Novimethylophilus kurashikiensis gen. nov. sp. nov., a new lanthanide-dependent methylotrophic species of Methylophilaceae.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1204-1223}, doi = {10.1111/1462-2920.14062}, pmid = {29411502}, issn = {1462-2920}, abstract = {Recently, it has been found that two types of methanol dehydrogenases (MDHs) exist in Gram-negative bacterial methylotrophs, calcium-dependent MxaFI-MDH and lanthanide-dependent XoxF-MDH and the latter is more widespread in bacterial genomes. We aimed to isolate and characterize lanthanide-dependent methylotrophs. The growth of strain La2-4T on methanol, which was isolated from rice rhizosphere soil, was strictly lanthanide dependent. Its 16S rRNA gene sequence showed only 93.4% identity to that of Methylophilus luteus MimT , and the name Novimethylophilus kurashikiensis gen. nov. sp. nov. is proposed. Its draft genome (ca. 3.69 Mbp, G + C content 56.1 mol%) encodes 3579 putative CDSs and 84 tRNAs. The genome harbors five xoxFs but no mxaFI. XoxF4 was the major MDH in the cells grown on methanol and methylamine, evidenced by protein identification and quantitative PCR analysis. Methylamine dehydrogenase gene was absent in the La2-4T genome, while genes for the glutamate-mediated methylamine utilization pathway were detected. The genome also harbors those for the tetrahydromethanopterin and ribulose monophosphate pathways. Additionally, as known species, isolates of Burkholderia ambifaria, Cupriavidus necator and Dyadobacter endophyticus exhibited lanthanide dependent growth on methanol. Thus, lanthanide can be used as an essential growth factor for methylotrophic bacteria that do not harbor MxaFI-MDH.}, } @article {pmid29411500, year = {2018}, author = {Arjona-Lopez, JM and Telengech, P and Jamal, A and Hisano, S and Kondo, H and Yelin, MD and Arjona-Girona, I and Kanematsu, S and Lopez-Herrera, CJ and Suzuki, N}, title = {Novel, diverse RNA viruses from Mediterranean isolates of the phytopathogenic fungus, Rosellinia necatrix: insights into evolutionary biology of fungal viruses.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1464-1483}, doi = {10.1111/1462-2920.14065}, pmid = {29411500}, issn = {1462-2920}, abstract = {To reveal mycovirus diversity, we conducted a search of as-yet-unexplored Mediterranean isolates of the phytopathogenic ascomycete Rosellinia necatrix for virus infections. Of seventy-nine, eleven fungal isolates tested RNA virus-positive, with many showing coinfections, indicating a virus incidence of 14%, which is slightly lower than that (approximately 20%) previously reported for extensive surveys of over 1000 Japanese R. necatrix isolates. All viral sequences were fully or partially characterized by Sanger and next-generation sequencing. These sequences appear to represent isolates of various new species spanning at least 6 established or previously proposed families such as Partiti-, Hypo-, Megabirna-, Yado-kari-, Fusagra- and Fusarividae, as well as a newly proposed family, Megatotiviridae. This observation greatly expands the diversity of R. necatrix viruses, because no hypo-, fusagra- or megatotiviruses were previously reported from R. necatrix. The sequence analyses showed a rare horizontal gene transfer event of the 2A-like protease domain between a dsRNA (phlegivirus) and a positive-sense, single-stranded RNA virus (hypovirus). Moreover, many of the newly detected viruses showed the closest relation to viruses reported from fungi other than R. necatrix, such as Fusarium spp., which are sympatric to R. necatrix. These combined results imply horizontal virus transfer between these soil-inhabitant fungi.}, } @article {pmid29411499, year = {2018}, author = {Zhang, X and St Leger, RJ and Fang, W}, title = {Stress-induced pyruvate accumulation contributes to cross protection in a fungus.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1158-1169}, doi = {10.1111/1462-2920.14058}, pmid = {29411499}, issn = {1462-2920}, abstract = {It is commonly observed that microorganisms subjected to a mild stress develop tolerance not only to higher doses of the same stress but also to other stresses - a phenomenon called cross protection. The mechanisms for cross protection have not been fully revealed. Here, we report that heat shock induced cross protection against UV, oxidative and osmotic/salt stress conditions in the cosmopolitan fungus Metarhizium robertsii. Similarly, oxidative and osmotic/salt stresses also induced cross protection against multiple other stresses. We found that oxidative and osmotic/salt stresses produce an accumulation of pyruvate that scavenges stress-induced reactive oxygen species and promotes fungal growth. Thus, stress-induced pyruvate accumulation contributes to cross protection. RNA-seq and qRT-PCR analyses showed that UV, osmotic/salt and oxidative stress conditions decrease the expression level of pyruvate consumption genes in the trichloroacetic acid cycle and fermentation pathways leading to pyruvate accumulation. Our work presents a novel mechanism for cross protection in microorganisms.}, } @article {pmid29411496, year = {2018}, author = {Morrissey, EM and Mau, RL and Schwartz, E and Koch, BJ and Hayer, M and Hungate, BA}, title = {Taxonomic patterns in the nitrogen assimilation of soil prokaryotes.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1112-1119}, doi = {10.1111/1462-2920.14051}, pmid = {29411496}, issn = {1462-2920}, abstract = {Nitrogen (N) is frequently a limiting nutrient in soil; its availability can govern ecosystem functions such as primary production and decomposition. Assimilation of N by microorganisms impacts the availability of N in soil. Despite its established ecological significance, the contributions of microbial taxa to N assimilation are unknown. Here we measure N uptake and use by microbial phylotypes and taxonomic groups within a diverse assemblage of soil microbes through quantitative stable isotope probing (qSIP) with 15 N. Following incubation with 15 NH4+, distinct patterns of 15 N assimilation among taxonomic groups were observed. For instance, glucose addition stimulated 15 N assimilation in most members of Actinobacteria and Proteobacteria but generally decreased 15 N use by Firmicutes and Bacteriodetes. While NH4+ is considered a preferred and universal source of N to prokaryotes, the majority (> 80%) of N assimilation in our soils could be attributed to a handful of active orders. Characterizing N assimilation of taxonomic groups with 15 N qSIP may provide a basis for understanding how microbial community composition influences N availability in the environment.}, } @article {pmid29411481, year = {2018}, author = {Zhu, L and Poosarla, VG and Song, S and Wood, TL and Miller, DS and Yin, B and Wood, TK}, title = {Glycoside hydrolase DisH from Desulfovibrio vulgaris degrades the N-acetylgalactosamine component of diverse biofilms.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14064}, pmid = {29411481}, issn = {1462-2920}, abstract = {Biofilms of sulfate-reducing bacteria (SRB) produce H2 S, which contributes to corrosion. Although bacterial cells in biofilms are cemented together, they often dissolve their own biofilm to allow the cells to disperse. Using Desulfovibrio vulgaris as a model SRB, we sought polysaccharide-degrading enzymes that disperse its biofilm. Using a whole-genome approach, we identified eight enzymes as putative extracellular glycoside hydrolases including DisH (DVU2239, dispersal hexosaminidase), an enzyme that we demonstrated here, by utilizing various p-nitrooligosaccharide substrates, to be an N-acetyl-β-D-hexosaminidase. For N-acetyl-β-D-galactosamine (GalNAc), Vmax was 3.6 µmol of p-nitrophenyl/min (mg protein)-1 and Km was 0.8 mM; the specific activity for N-acetyl β-D-glucosamine (GlcNAc) was 7.8 µmol of p-nitrophenyl/min (mg protein)-1 . Since GalNAc is one of the three exopolysaccharide matrix components of D. vulgaris, purified DisH was found to disperse 63 ± 2% biofilm as well as inhibit biofilm formation up to 47 ± 4%. The temperature and pH optima are 60°C and pH 6, respectively; DisH is also inhibited by copper and is secreted. In addition, since polymers of GalNAc and GlcNAc are found in the matrix of diverse bacteria, DisH dispersed biofilms of Pseudomonas aeruginosa, Escherichia coli and Bacillus subtilis. Therefore, DisH has the potential to inhibit and disperse a wide-range of biofilms.}, } @article {pmid29411480, year = {2018}, author = {Brar, GS and Ali, S and Qutob, D and Ambrose, S and Lou, K and Maclachlan, R and Pozniak, CJ and Fu, YB and Sharpe, AG and Kutcher, HR}, title = {Genome re-sequencing and simple sequence repeat markers reveal the existence of divergent lineages in the Canadian Puccinia striiformis f. sp. tritici population with extensive DNA methylation.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1498-1515}, doi = {10.1111/1462-2920.14067}, pmid = {29411480}, issn = {1462-2920}, abstract = {Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is an important disease in Canada. The worldwide genetic structure of Pst populations have been characterized, excluding Canada. Here, we elucidated the genetic structure of the western Canadian Pst population using molecular markers, revealing the presence of four divergent lineages with predominantly clonal structure. In the worldwide context, two previously reported lineages were identified: PstS0 (22%), representing an old Northwestern-European and PstS1 (35%), an invasive warm-temperature adapted. Additionally, two new, unreported lineages, PstPr (9%) and PstS1-related (35%), were detected, which produced more telia than other lineages and had double the number of unique recombination events. The PstPr was a recent invasion, and likely evolved in a diverse, recombinant population as it was closely related to the PstS5, PstS7/Warrior, PstS8/Kranich, and PstS9 lineages originating from sexually recombining populations in the centre of diversity. The DNA methylation analysis revealed DNA-methyltransferase1-homologs, providing compelling evidence for epigenetic regulation and as a first report, an average of ∼5%, 5hmC in the Puccinia epigenome merits further investigation. The divergent lineages in the Canadian Pst population with the potential for genetic recombination, as well as epigenetic regulation needs consideration in the context of pathogen adaptation and management.}, } @article {pmid29411478, year = {2018}, author = {Li, B and Dong, X and Li, X and Chen, H and Zhang, H and Zheng, X and Zhang, Z}, title = {A subunit of the HOPS endocytic tethering complex, FgVps41, is important for fungal development and plant infection in Fusarium graminearum.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1436-1451}, doi = {10.1111/1462-2920.14050}, pmid = {29411478}, issn = {1462-2920}, abstract = {The signals by which eukaryotic cells communicate with the environment are usually mediated by vesicle trafficking to be attenuated or terminated. However, vesicle trafficking-mediated signal transmission during interactions between pathogens and host plants is poorly understood. Here, we identified and characterized the vacuole sorting protein FgVps41, which is the yeast HOPS tethering complex subunit Vps41 homolog in Fusarium graminearum. Targeted gene deletion demonstrated that FgVps41 is important for vegetative growth, asexual/sexual development, conidial morphology, plant infection and deoxynivalenol production. Cellular localization and cytological examinations revealed that FgVps41 localizes to early/late endosomes and vacuole membrane, and is recruited to prevacuolar compartments and vacuole membrane by interacting with FgRab7 in F. graminearum. Furthermore, we found FgVps41 mediates vacuole membrane fusion and sorting of FgApeI, a cargo protein involving in the cytosol-to-vacuole targeting pathway. In addition, we found that FgVps41 interacts with FgYck3, a vacuolar type I casein kinase, which regulates vesicle fusion in the AP-3 pathway. Deletion of FgYck3 showed similar phenotypes to the ΔFgvps41 mutant, and both FgRab7 and FgYck3 regulate the normal localization of FgVps41. Collectively, our results demonstrate that FgVps41 acts as a HOPS tethering complex subunit and is important for the development of infection-related morphogenesis in F. graminearum.}, } @article {pmid29410785, year = {2018}, author = {Archetti, M}, title = {Cooperation between cancer cells.}, journal = {Evolution, medicine, and public health}, volume = {2018}, number = {1}, pages = {1}, pmid = {29410785}, issn = {2050-6201}, } @article {pmid29410353, year = {2018}, author = {Rose, JP and Kleist, TJ and Löfstrand, SD and Drew, BT and Schönenberger, J and Sytsma, KJ}, title = {Phylogeny, historical biogeography, and diversification of angiosperm order Ericales suggest ancient Neotropical and East Asian connections.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {59-79}, doi = {10.1016/j.ympev.2018.01.014}, pmid = {29410353}, issn = {1095-9513}, mesh = {Animals ; *Biodiversity ; Chloroplasts/genetics ; Far East ; Fossils/history ; Genetic Speciation ; History, Ancient ; Magnoliopsida/*classification/genetics ; Mitochondria/genetics ; *Phylogeny ; Phylogeography/history ; Ribosomes/genetics ; }, abstract = {Inferring interfamilial relationships within the eudicot order Ericales has remained one of the more recalcitrant problems in angiosperm phylogenetics, likely due to a rapid, ancient radiation. As a result, no comprehensive time-calibrated tree or biogeographical analysis of the order has been published. Here, we elucidate phylogenetic relationships within the order and then conduct time-dependent biogeographical and diversification analyses by using a taxon and locus-rich supermatrix approach on one-third of the extant species diversity calibrated with 23 macrofossils and two secondary calibration points. Our results corroborate previous studies and also suggest several new but poorly supported relationships. Newly suggested relationships are: (1) holoparasitic Mitrastemonaceae is sister to Lecythidaceae, (2) the clade formed by Mitrastemonaceae + Lecythidaceae is sister to Ericales excluding balsaminoids, (3) Theaceae is sister to the styracoids + sarracenioids + ericoids, and (4) subfamilial relationships with Ericaceae suggest that Arbutoideae is sister to Monotropoideae and Pyroloideae is sister to all subfamilies excluding Arbutoideae, Enkianthoideae, and Monotropoideae. Our results indicate Ericales began to diversify 110 Mya, within Indo-Malaysia and the Neotropics, with exchange between the two areas and expansion out of Indo-Malaysia becoming an important area in shaping the extant diversity of many families. Rapid cladogenesis occurred along the backbone of the order between 104 and 106 Mya. Jump dispersal is important within the order in the last 30 My, but vicariance is the most important cladogenetic driver of disjunctions at deeper levels of the phylogeny. We detect between 69 and 81 shifts in speciation rate throughout the order, the vast majority of which occurred within the last 30 My. We propose that range shifting may be responsible for older shifts in speciation rate, but more recent shifts may be better explained by morphological innovation.}, } @article {pmid29410165, year = {2018}, author = {Wang, Y and Yin, S and Xue, H and Yang, Y and Zhang, N and Zhao, P}, title = {Mid-gestational sevoflurane exposure inhibits fetal neural stem cell proliferation and impairs postnatal learning and memory function in a dose-dependent manner.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {185-197}, doi = {10.1016/j.ydbio.2018.01.022}, pmid = {29410165}, issn = {1095-564X}, mesh = {Anesthetics, Inhalation/administration & dosage/*toxicity ; Animals ; Cell Division/drug effects ; Cyclin D1/biosynthesis ; Dose-Response Relationship, Drug ; Female ; Fetus/*drug effects ; Gestational Age ; Glycogen Synthase Kinase 3 beta/antagonists & inhibitors/metabolism ; Hippocampus/drug effects/embryology/metabolism ; Hyaluronan Receptors/biosynthesis ; Learning Disorders/*chemically induced ; Lithium Chloride/therapeutic use ; Maze Learning/drug effects ; Memory Disorders/*chemically induced ; Methyl Ethers/administration & dosage/antagonists & inhibitors/*toxicity ; Nerve Tissue Proteins/antagonists & inhibitors/metabolism ; Neural Stem Cells/cytology/*drug effects ; Pregnancy ; *Prenatal Exposure Delayed Effects ; Rats ; Rats, Sprague-Dawley ; Sevoflurane ; Spatial Behavior/drug effects ; Wnt Signaling Pathway/drug effects ; }, abstract = {Advancements in fetal intervention procedures have led to increases in the number of pregnant women undergoing general anesthesia during the second trimester-a period characterized by extensive proliferation of fetal neural stem cells (NSCs). However, few studies have investigated the effects of mid-gestational sevoflurane exposure on fetal NSC proliferation or postnatal learning and memory function. In the present study, pregnant rats were randomly assigned to a control group (C group), a low sevoflurane concentration group (2%; L group), a high sevoflurane concentration group (3.5%; H group), a high sevoflurane concentration plus lithium chloride group (H + Li group), and a lithium chloride group (Li group) at gestational day 14. Rats received different concentrations of sevoflurane anesthesia for 2 h. The offspring rats were weaned at 28 days for behavioral testing (i.e., Morris Water Maze [MWM]), and fetal brains or postnatal hippocampal tissues were harvested for immunofluorescence staining, real-time PCR, and Western blotting analyses in order to determine the effect of sevoflurane exposure on NSC proliferation and the Wnt/β-catenin signaling pathway. Our results indicated that maternal exposure to 3.5% sevoflurane (H group) during the mid-gestational period impaired the performance of offspring rats in the MWM test, reduced NSC proliferation, and increased protein levels of fetal glycogen synthase kinase-3 beta (GSK-3β). Such treatment also decreased levels of β-catenin protein, CD44 RNA, and Cyclin D1 RNA relative to those observed in the C group. However, these effects were transiently attenuated by treatment with lithium chloride. Conversely, maternal exposure to 2% sevoflurane (L group) did not influence NSC proliferation or the Wnt signaling pathway. Our results suggest that sevoflurane exposure during the second trimester inhibits fetal NSC proliferation via the Wnt/β-catenin pathway and impairs postnatal learning and memory function in a dose-dependent manner.}, } @article {pmid29409984, year = {2018}, author = {Sabbag, AF and Lyra, ML and Zamudio, KR and Haddad, CFB and Feio, RN and Leite, FSF and Gasparini, JL and Brasileiro, CA}, title = {Molecular phylogeny of Neotropical rock frogs reveals a long history of vicariant diversification in the Atlantic forest.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {142-156}, doi = {10.1016/j.ympev.2018.01.017}, pmid = {29409984}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Brazil ; DNA, Mitochondrial/chemistry/isolation & purification/metabolism ; Ecosystem ; Forests ; Genetic Variation ; *Phylogeny ; Ranidae/*classification/genetics ; Sequence Analysis, DNA ; }, abstract = {The Brazilian Atlantic coastal forest is one of the most heterogeneous morphoclimatic domains on earth and is thus an excellent region in which to examine the role that habitat heterogeneity plays in shaping diversification of lineages and species. Here we present a molecular phylogeny of the rock frogs of the genus Thoropa Cope, 1865, native to the Atlantic forest and extending to adjacent campo rupestre of Brazil. The goal of this study is to reconstruct the evolutionary history of the genus using multilocus molecular phylogenetic analyses. Our topology reveals 12 highly supported lineages among the four nominal species included in the study. Species T. saxatilis and T. megatympanum are monophyletic. Thoropa taophora is also monophyletic, but nested within T. miliaris. Populations of T. miliaris cluster in five geographically distinct lineages, with low support for relationships among them. Although all 12 lineages are geographically structured, some T. miliaris lineages have syntopic distributions with others, likely reflecting a secondary contact zone between divergent lineages. We discuss a biogeographic scenario that best explains the order of divergence and the distribution of species in Atlantic forest and adjacent areas, and outline the implications of our findings for the taxonomy of Thoropa.}, } @article {pmid29409983, year = {2018}, author = {Hassan, KA and Liu, Q and Elbourne, LDH and Ahmad, I and Sharples, D and Naidu, V and Chan, CL and Li, L and Harborne, SPD and Pokhrel, A and Postis, VLG and Goldman, A and Henderson, PJF and Paulsen, IT}, title = {Pacing across the membrane: the novel PACE family of efflux pumps is widespread in Gram-negative pathogens.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {450-454}, pmid = {29409983}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biological Transport ; Disinfectants/metabolism ; Gram-Negative Bacteria/chemistry/genetics/*metabolism ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; *Multigene Family ; Proteobacteria/chemistry/genetics/metabolism ; }, abstract = {The proteobacterial antimicrobial compound efflux (PACE) family of transport proteins was only recently described. PACE family transport proteins can confer resistance to a range of biocides used as disinfectants and antiseptics, and are encoded by many important Gram-negative human pathogens. However, we are only just beginning to appreciate the range of functions and the mechanism(s) of transport operating in these proteins. Genes encoding PACE family proteins are typically conserved in the core genomes of bacterial species rather than on recently acquired mobile genetic elements, suggesting that they confer important core functions in addition to biocide resistance. Three-dimensional structural information is not yet available for PACE family proteins. However, PACE proteins have several very highly conserved amino acid sequence motifs that are likely to be important for substrate transport. PACE proteins also display strong amino acid sequence conservation between their N and C-terminal halves, suggesting that they evolved by duplication of an ancestral protein comprised of two transmembrane helices. In light of their drug resistance functions in Gram-negative pathogens, PACE proteins should be the subject of detailed future investigation.}, } @article {pmid29409906, year = {2018}, author = {Leduc, D and Zhao, ZQ and Verdon, V and Xu, Y}, title = {Phylogenetic position of the enigmatic deep-sea nematode order Rhaptothyreida: A molecular analysis.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {29-36}, doi = {10.1016/j.ympev.2018.01.018}, pmid = {29409906}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Ribosomal/chemistry/classification/genetics ; Nematoda/*classification/genetics ; New Zealand ; Phylogeny ; Ribosome Subunits/chemistry/classification/genetics ; Sequence Analysis, DNA ; }, abstract = {The placement of the rare deep-sea nematode order Rhaptothyreida remains unclear due to the unique morphology of this group, an unknown life cycle with morphologically distinct juvenile stages which may or may not be parasitic, and lack of molecular sequences. Here, we investigate the phylogenetic placement and status of the Rhaptothyreida based on SSU and D2-D3 of LSU rDNA sequences of Rhaptothyerus typicus specimens obtained from the continental slope of New Zealand. Molecular sequences of three adults and a late stage juvenile were identical, confirming that they belong to the same species despite pronounced morphological differences. We observed the presence of the rare nucleotide transition A → G and transversion G → Y in the loops of Hairpin 35 and 48 regions, which is consistent with the placement of R. typicus within the order Enoplida. Rhaptothyreus typicus was consistently recovered as a long branch clade in SSU and D2-D3 of LSU analyses, which can have a destabilising effect on tree topology. After Gblocks were used to remove sites of questionable alignment, R. typicus was placed in a clade comprising Trissonchulus, Dolicholaimus and Ironus sequences (family Ironidae, order Enoplida) in both Bayesian and Maximum Likelihood SSU topologies. Depending on which alignment algorithm was used, analyses of LSU sequences focusing on enoplid taxa either suggested a relationship between R. typicus and Halalaimus (family Oxystominidae) or did not identify any clear relationships. Overall, our results provide strong evidence for placing R. typicus and the family Rhaptothyreidae within the order Enoplida, although further work is required to clarify relationships between rhaptothyreids and other enoplid taxa. A parasitic lifestyle could explain the unique morphology of this group, their highly divergent SSU and LSU rDNA molecular sequences, and the marked morphological differences between late juveniles and adults. Further molecular investigations targeting both free-living and parasitic early juvenile life stages in potential deep-sea hosts are needed to better understand the evolution of this unusual nematode taxon.}, } @article {pmid29409769, year = {2018}, author = {Kague, E and Witten, PE and Soenens, M and Campos, CL and Lubiana, T and Fisher, S and Hammond, C and Brown, KR and Passos-Bueno, MR and Huysseune, A}, title = {Zebrafish sp7 mutants show tooth cycling independent of attachment, eruption and poor differentiation of teeth.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {176-184}, doi = {10.1016/j.ydbio.2018.01.021}, pmid = {29409769}, issn = {1095-564X}, support = {19476//Arthritis Research UK/United Kingdom ; 21211//Arthritis Research UK/United Kingdom ; }, mesh = {Alveolar Process/pathology ; Animals ; Animals, Genetically Modified ; Dental Pulp/pathology ; Dentin/abnormalities ; Dentinogenesis/*genetics/physiology ; Gene Expression Regulation, Developmental ; Genes, Reporter ; Odontoblasts/pathology ; Odontogenesis/*genetics/physiology ; Osteoclasts/metabolism ; Regeneration ; Sp7 Transcription Factor/deficiency/genetics/*physiology ; Tooth Abnormalities/*genetics ; Tooth Root/pathology ; Zebrafish/*genetics ; Zebrafish Proteins/deficiency/genetics/*physiology ; }, abstract = {The capacity to fully replace teeth continuously makes zebrafish an attractive model to explore regeneration and tooth development. The requirement of attachment bone for the appearance of replacement teeth has been hypothesized but not yet investigated. The transcription factor sp7 (osterix) is known in mammals to play an important role during odontoblast differentiation and root formation. Here we study tooth replacement in the absence of attachment bone using sp7 zebrafish mutants. We analysed the pattern of tooth replacement at different stages of development and demonstrated that in zebrafish lacking sp7, attachment bone is never present, independent of the stage of tooth development or fish age, yet replacement is not interrupted. Without bone of attachment we observed abnormal orientation of teeth, and abnormal connection of pulp cavities of predecessor and replacement teeth. Mutants lacking sp7 show arrested dentinogenesis, with non-polarization of odontoblasts and only a thin layer of dentin deposited. Osteoclast activity was observed in sp7 mutants; due to the lack of bone of attachment, remodelling was diminished but nevertheless present along the pharyngeal bone. We conclude that tooth replacement is ongoing in the sp7 mutant despite poor differentiation and defective attachment. Without bone of attachment tooth orientation and pulp organization are compromised.}, } @article {pmid29409661, year = {2018}, author = {Kondrashov, AS}, title = {Through Sex, Nature Is Telling Us Something Important.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {352-361}, doi = {10.1016/j.tig.2018.01.003}, pmid = {29409661}, issn = {0168-9525}, mesh = {Animals ; *Biological Evolution ; Genotype ; Male ; Reproduction/*genetics ; Selection, Genetic/*genetics ; }, abstract = {Theoretically, a variety of mechanisms can make amphimixis advantageous due to reshuffling of offspring genotypes. Recently, it has been shown experimentally that some of these mechanisms can indeed work in artificial populations. However, we still do not know which of them, if any, are relevant in nature, and the available indirect estimates seem to suggest that neither negative nor positive selection in natural populations is strong enough to provide evolutionary protection for obligate amphimixis. Thus, progress in understanding the evolution of amphimixis will depend on direct measurements of the strength of natural selection.}, } @article {pmid29409543, year = {2018}, author = {Zha, Y and Eiler, A and Johansson, F and Svanbäck, R}, title = {Effects of predation stress and food ration on perch gut microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {28}, pmid = {29409543}, issn = {2049-2618}, support = {VR - 2011-05646//Vetenskapsrådet/International ; ICA10-0015//Stiftelsen för Strategisk Forskning/International ; }, mesh = {Animals ; Bacteria/*classification/genetics/isolation & purification/metabolism ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Esocidae/physiology ; Female ; Gastrointestinal Microbiome ; High-Throughput Nucleotide Sequencing ; Male ; Perches/*microbiology ; Predatory Behavior ; RNA, Ribosomal, 16S/*genetics ; Secondary Metabolism ; Sequence Analysis, DNA/*methods ; *Stress, Physiological ; }, abstract = {BACKGROUND: Gut microbiota provide functions of importance to influence hosts' food digestion, metabolism, and protection against pathogens. Factors that affect the composition and functions of gut microbial communities are well studied in humans and other animals; however, we have limited knowledge of how natural food web factors such as stress from predators and food resource rations could affect hosts' gut microbiota and how it interacts with host sex. In this study, we designed a two-factorial experiment exposing perch (Perca fluviatilis) to a predator (pike, Esox lucius), and different food ratios, to examine the compositional and functional changes of perch gut microbiota based on 16S rRNA amplicon sequencing. We also investigated if those changes are host sex dependent.

RESULTS: We showed that overall gut microbiota composition among individual perch significantly responded to food ration and predator presence. We found that species richness decreased with predator presence, and we identified 23 taxa from a diverse set of phyla that were over-represented when a predator was present. For example, Fusobacteria increased both at the lowest food ration and at predation stress conditions, suggesting that Fusobacteria are favored by stressful situations for the host. In concordance, both food ration and predation stress seemed to influence the metabolic repertoire of the gut microbiota, such as biosynthesis of other secondary metabolites, metabolism of cofactors, and vitamins. In addition, the identified interaction between food ration and sex emphasizes sex-specific responses to diet quantity in gut microbiota.

CONCLUSIONS: Collectively, our findings emphasize an alternative state in gut microbiota with responses to changes in natural food webs depending on host sex. The obtained knowledge from this study provided us with an important perspective on gut microbiota in a food web context.}, } @article {pmid29409541, year = {2018}, author = {Lebellenger, L and Verrez-Bagnis, V and Passerini, D and Delbarre-Ladrat, C}, title = {Comparative genomics reveals a widespread distribution of an exopolysaccharide biosynthesis gene cluster among Vibrionaceae.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {102}, pmid = {29409541}, issn = {1756-0500}, mesh = {Biosynthetic Pathways/*genetics ; Genome, Bacterial/*genetics ; Genomics/*methods ; Multigene Family/*genetics ; Polysaccharides, Bacterial/*biosynthesis ; Vibrionaceae/*genetics ; }, abstract = {OBJECTIVES: The eps locus in Vibrio diabolicus is involved in the production of the biotechnologically valuable HE800 EPS. In this study, the distribution and diversity of similar eps gene clusters across Vibrionaceae and its variability in relation to phylogenetic relationship were investigated. The aim was to provide a better knowledge of the eps gene cluster importance and to facilitate discovery of new EPS with potent interesting bioactivities.

RESULTS: Seventy percent of the 103 genome sequences examined display such an eps locus with a high level of synteny. However, genetic divergence was found inside some monophyletic clades or even between some strains of the same species. It includes gene insertions, truncations, and deletions. Comparative analysis also reveals some variations in glycosyltransferase and export systems genes. Phylogenetic analysis of the Vibrionaceae eps gene clusters within Vibrionaceae suggests a vertical transfer by speciation but also pinpoints rearrangement events independent of the speciation.}, } @article {pmid29409538, year = {2018}, author = {Bernhardt, P and Kratzer, W and Schmidberger, J and Graeter, T and Gruener, B and , }, title = {Laboratory parameters in lean NAFLD: comparison of subjects with lean NAFLD with obese subjects without hepatic steatosis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {101}, pmid = {29409538}, issn = {1756-0500}, support = {GrK1041//Deutsche Forschungsgemeinschaft/ ; }, mesh = {Adult ; Aged ; *Body Mass Index ; Cholesterol/*blood ; Cholesterol, LDL/blood ; Female ; Ferritins/*blood ; *Hematocrit ; Hemoglobins/*analysis ; Humans ; *Insulin Resistance ; Male ; Middle Aged ; Non-alcoholic Fatty Liver Disease/*blood ; Obesity/*blood ; Triglycerides/*blood ; Young Adult ; }, abstract = {OBJECTIVE: Search for meaningful laboratory and anthropometric parameters in lean non-alcoholic fatty liver disease (lean NAFLD) in the general population. Out of 2445 subjects in a random population sample, we compared those who had a body mass index (BMI) < 25 and a fatty liver [lean NAFLD (LN), n = 5] with obese subjects who had a BMI > 30 but no fatty liver [non-NAFLD (NN), n = 27] in a follow-up examination. Ultrasonic, anthropometric and laboratory parameters were collected.

RESULTS: There were significant differences (p < 0.05) between the LN and the NN groups with respect to serum ferritin (199.2 ± 72.1 LN vs 106.0 ± 89.6 NN), haemoglobin (14.9 ± 0.8 LN vs 13.5 ± 1.2 NN), haematocrit (0.438 ± 0.019 LN vs 0.407 ± 0.035 NN) and Mean corpuscular haemoglobin concentration (34 ± 0.6 LN vs 33.2 ± 0.8 NN). Significantly lower values of soluble transferrin receptor were measured in the LN group (2.8 ± 0.4 LN vs 3.8 ± 1.5 NN). In both groups, the measured HOMA-IR index (homeostatic model assessment of insulin resistance index) (2.3; normal range ≤ 1) was abnormal. Mean cholesterol (6.2 ± 1.4 LN and 5.6 ± 1.1 NN) and low-density lipoprotein levels (3.8 ± 1.0 LN 3.4 ± 0.9 NN) were above the upper limit of normal in both groups, as was the mean triglycerides level in the LN group (2.6 ± 2.0). In summary, there are differences in parameters of iron and fat metabolism between subjects with LN and overweight subjects without fatty liver infiltration.}, } @article {pmid29409534, year = {2018}, author = {Tachedjian, G and O'Hanlon, DE and Ravel, J}, title = {The implausible "in vivo" role of hydrogen peroxide as an antimicrobial factor produced by vaginal microbiota.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {29}, pmid = {29409534}, issn = {2049-2618}, support = {R01 NR015495/NR/NINR NIH HHS/United States ; U19AI084044//National Institute of Allergy and Infectious Diseases/International ; R01NR015495/NR/NINR NIH HHS/United States ; U19 AI084044/AI/NIAID NIH HHS/United States ; APP1088564//National Health and Medical Research Council/International ; APP1117748//National Health and Medical Research Council (AU)/International ; }, mesh = {Anti-Infective Agents/chemistry/*pharmacology ; Cell Hypoxia ; Female ; Genome, Bacterial ; Humans ; Hydrogen Peroxide/*chemistry/pharmacology ; Lactic Acid/chemistry/*pharmacology ; Lactobacillus/*chemistry ; Microbiota ; Vagina/*microbiology ; }, abstract = {In the cervicovaginal environment, the production of hydrogen peroxide (H2O2) by vaginal Lactobacillus spp. is often mentioned as a critical factor to the in vivo vaginal microbiota antimicrobial properties. We present several lines of evidence that support the implausibility of H2O2 as an "in vivo" contributor to the cervicovaginal milieu antimicrobial properties. An alternative explanation is proposed, supported by previous reports ascribing protective and antimicrobial properties to other factors produced by Lactobacillus spp. capable of generating H2O2. Under this proposal, lactic acid rather than H2O2 plays an important role in the antimicrobial properties of protective vaginal Lactobacillus spp. We hope this commentary will help future research focus on more plausible mechanisms by which vaginal Lactobacillus spp. exert their antimicrobial and beneficial properties, and which have in vivo and translational relevance.}, } @article {pmid29409524, year = {2018}, author = {Akoachere, JTK and Tatsinkou, BF and Nkengfack, JM}, title = {Bacterial and parasitic contaminants of salad vegetables sold in markets in Fako Division, Cameroon and evaluation of hygiene and handling practices of vendors.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {100}, pmid = {29409524}, issn = {1756-0500}, mesh = {*Anti-Bacterial Agents ; Bacteria, Aerobic/*isolation & purification ; Balantidium/*isolation & purification ; Cameroon ; Commerce ; *Drug Resistance, Bacterial ; Entamoeba/*isolation & purification ; Enterobacteriaceae/*isolation & purification ; *Erythromycin ; *Food Contamination ; *Food Handling ; Humans ; Hygiene ; Staphylococcus aureus/*isolation & purification ; *Vegetables/microbiology/parasitology ; }, abstract = {OBJECTIVE: Increase in awareness of the health benefits of vegetables has resulted in an increase in consumption. Many vegetables are consumed raw to retain the natural taste and heat labile nutrients. The safety of raw vegetables is a great concern. We investigated the bacteriological and parasitological quality of salad vegetables sold in three major markets in Fako Division Cameroon, the hygiene and preservation practices of vendors and determined the antimicrobial sensitivity of bacterial isolates, to provide data that could be used to improve food safety and safeguard public health.

RESULTS: Bacterial contamination was high. Mean aerobic bacteria counts ranged from 2.5 × 106 to 15 × 106 cfu/g, total coliform counts from 4 to > 2400/g and fecal coliforms < 3 to 1100/g. Six bacterial species were isolated among which Staphylococcus aureus (35.4%) predominated while Serratia marcescens (8.5%) was the least. Bacteria showed high resistance to erythromycin (87.6%). Ten parasitic organisms were detected. Balantidium coli (25.6%) and Entamoeba spp. (21.7%) predominated. Contamination was highest in lettuce and lowest in green pepper. Hygiene and vegetable preservation practices of vendors were poor and could aggravate contamination. Contamination of fresh salad vegetables with pathogenic bacteria and parasites could be a food safety concern in study area.}, } @article {pmid29409472, year = {2018}, author = {Mekonnen, A and Fashing, PJ and Bekele, A and Hernandez-Aguilar, RA and Rueness, EK and Stenseth, NC}, title = {Dietary flexibility of Bale monkeys (Chlorocebus djamdjamensis) in southern Ethiopia: effects of habitat degradation and life in fragments.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {4}, pmid = {29409472}, issn = {1472-6785}, support = {D/5133-1//International Foundation for Science/International ; }, abstract = {BACKGROUND: Understanding the effects of habitat modification on the feeding strategies of threatened species is essential to designing effective conservation management plans. Bale monkeys (Chlorocebus djamdjamensis) are endemic to the rapidly shrinking montane forests of the southern Ethiopian Highlands. Most populations inhabit continuous bamboo forest subsisting largely on the young leaves and shoots of a single species of bamboo. Because of habitat disturbance in recent decades, however, there are now also several dozen small populations inhabiting isolated forest fragments where bamboo has been degraded. During 12-months, we assessed Bale monkey responses to habitat degradation by comparing habitat composition, phenological patterns, and feeding ecology in a largely undisturbed continuous forest (Continuous groups A and B) and in two fragments (Patchy and Hilltop groups).

RESULTS: We found that habitat quality and food availability were much lower in fragments than in continuous forest. In response to the relative scarcity of bamboo in fragments, Bale monkeys spent significantly less time feeding on the young leaves and shoots of bamboo and significantly more time feeding on non-bamboo young leaves, fruits, seeds, stems, petioles, and insects in fragments than in continuous forest. Groups in fragments also broadened their diets to incorporate many more plant species (Patchy: ≥ 47 and Hilltop: ≥ 35 species)-including several forbs, graminoids and cultivated crops-than groups in continuous forest (Continuous A: 12 and Continuous B: 8 species). Nevertheless, bamboo was still the top food species for Patchy group (30% of diet) as well as for both continuous forest groups (mean = 81%). However, in Hilltop group, for which bamboo was especially scarce, Bothriochloa radicans (Poaceae), a grass, was the top dietary species (15% of diet) and bamboo ranked 10th (2%).

CONCLUSIONS: We demonstrate that Bale monkeys are more dietarily flexible than previously thought and able to cope with some degradation of their primary bamboo forest habitat. However, crop raiding and other terrestrial foraging habits more common among fragment groups may place them at greater risk of hunting by humans. Thus, longitudinal monitoring is necessary to evaluate the long-term viability of Bale monkey populations in fragmented habitats.}, } @article {pmid29409454, year = {2018}, author = {Frailey, DC and Chaluvadi, SR and Vaughn, JN and Coatney, CG and Bennetzen, JL}, title = {Gene loss and genome rearrangement in the plastids of five Hemiparasites in the family Orobanchaceae.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {30}, pmid = {29409454}, issn = {1471-2229}, support = {2012-67013-19473//USDA/NIFA/International ; }, mesh = {Chloroplasts/*genetics ; *Gene Deletion ; *Genes, Plant ; *Genome, Chloroplast ; *Genome, Plant ; Orobanchaceae/*genetics ; }, abstract = {BACKGROUND: The chloroplast genomes (plastome) of most plants are highly conserved in structure, gene content, and gene order. Parasitic plants, including those that are fully photosynthetic, often contain plastome rearrangements. These most notably include gene deletions that result in a smaller plastome size. The nature of gene loss and genome structural rearrangement has been investigated in several parasitic plants, but their timing and contributions to the adaptation of these parasites requires further investigation, especially among the under-studied hemi-parasites.

RESULTS: De novo sequencing, assembly and annotation of the chloroplast genomes of five photosynthetic parasites from the family Orobanchaceae were employed to investigate plastome dynamics. Four had major structural rearrangements, including gene duplications and gene losses, that differentiated the taxa. The facultative parasite Aureolaria virginica had the most similar genome content to its close non-parasitic relative, Lindenbergia philippensis, with similar genome size and organization, and no differences in gene content. In contrast, the facultative parasite Buchnera americana and three obligate parasites in the genus Striga all had enlargements of their plastomes, primarily caused by expansion within the large inverted repeats (IRs) that are a standard plastome feature. Some of these IR increases were shared by multiple investigated species, but others were unique to particular lineages. Gene deletions and pseudogenization were also both shared and lineage-specific, with particularly frequent and independent loss of the ndh genes involved in electron recycling.

CONCLUSIONS: Five new plastid genomes were fully assembled and compared. The results indicate that plastome instability is common in parasitic plants, even those that retain the need to perform essential plastid functions like photosynthesis. Gene losses were slow and not identical across taxa, suggesting that different lineages had different uses or needs for some of their plastome gene content, including genes involved in some aspects of photosynthesis. Recent repeat region extensions, some unique to terminal species branches, were observed after the divergence of the Buchnera/Striga clade, suggesting that this otherwise rare event has some special value in this lineage.}, } @article {pmid29409451, year = {2018}, author = {Sivasakthi, K and Thudi, M and Tharanya, M and Kale, SM and Kholová, J and Halime, MH and Jaganathan, D and Baddam, R and Thirunalasundari, T and Gaur, PM and Varshney, RK and Vadez, V}, title = {Plant vigour QTLs co-map with an earlier reported QTL hotspot for drought tolerance while water saving QTLs map in other regions of the chickpea genome.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {29}, pmid = {29409451}, issn = {1471-2229}, support = {Capital funding for the LeasyScan platform//ICRISAT/International ; }, mesh = {Adaptation, Physiological ; Cicer/genetics/*physiology ; *Droughts ; Genetic Variation ; *Genome, Plant ; Phenotype ; *Quantitative Trait Loci ; Water/*metabolism ; }, abstract = {BACKGROUND: Terminal drought stress leads to substantial annual yield losses in chickpea (Cicer arietinum L.). Adaptation to water limitation is a matter of matching water supply to water demand by the crop. Therefore, harnessing the genetics of traits contributing to plant water use, i.e. transpiration rate and canopy development dynamics, is important to design crop ideotypes suited to a varying range of water limited environments. With an aim of identifying genomic regions for plant vigour (growth and canopy size) and canopy conductance traits, 232 recombinant inbred lines derived from a cross between ICC 4958 and ICC 1882, were phenotyped at vegetative stage under well-watered conditions using a high throughput phenotyping platform (LeasyScan).

RESULTS: Twenty one major quantitative trait loci (M-QTLs) were identified for plant vigour and canopy conductance traits using an ultra-high density bin map. Plant vigour traits had 13 M-QTLs on CaLG04, with favourable alleles from high vigour parent ICC 4958. Most of them co-mapped with a previously fine mapped major drought tolerance "QTL-hotspot" region on CaLG04. One M-QTL was found for canopy conductance on CaLG03 with the ultra-high density bin map. Comparative analysis of the QTLs found across different density genetic maps revealed that QTL size reduced considerably and % of phenotypic variation increased as marker density increased.

CONCLUSION: Earlier reported drought tolerance hotspot is a vigour locus. The fact that canopy conductance traits, i.e. the other important determinant of plant water use, mapped on CaLG03 provides an opportunity to manipulate these loci to tailor recombinants having low/high transpiration rate and plant vigour, fitted to specific drought stress scenarios in chickpea.}, } @article {pmid29409446, year = {2018}, author = {Daberdaku, S and Ferrari, C}, title = {Exploring the potential of 3D Zernike descriptors and SVM for protein-protein interface prediction.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {35}, pmid = {29409446}, issn = {1471-2105}, support = {CPDR150813/15 "Models and Algorithms for Protein-Protein Docking"//Università degli Studi di Padova/International ; }, mesh = {Amino Acids/chemistry ; Area Under Curve ; Binding Sites ; Protein Interaction Domains and Motifs ; Proteins/*chemistry/metabolism ; ROC Curve ; *Support Vector Machine ; }, abstract = {BACKGROUND: The correct determination of protein-protein interaction interfaces is important for understanding disease mechanisms and for rational drug design. To date, several computational methods for the prediction of protein interfaces have been developed, but the interface prediction problem is still not fully understood. Experimental evidence suggests that the location of binding sites is imprinted in the protein structure, but there are major differences among the interfaces of the various protein types: the characterising properties can vary a lot depending on the interaction type and function. The selection of an optimal set of features characterising the protein interface and the development of an effective method to represent and capture the complex protein recognition patterns are of paramount importance for this task.

RESULTS: In this work we investigate the potential of a novel local surface descriptor based on 3D Zernike moments for the interface prediction task. Descriptors invariant to roto-translations are extracted from circular patches of the protein surface enriched with physico-chemical properties from the HQI8 amino acid index set, and are used as samples for a binary classification problem. Support Vector Machines are used as a classifier to distinguish interface local surface patches from non-interface ones. The proposed method was validated on 16 classes of proteins extracted from the Protein-Protein Docking Benchmark 5.0 and compared to other state-of-the-art protein interface predictors (SPPIDER, PrISE and NPS-HomPPI).

CONCLUSIONS: The 3D Zernike descriptors are able to capture the similarity among patterns of physico-chemical and biochemical properties mapped on the protein surface arising from the various spatial arrangements of the underlying residues, and their usage can be easily extended to other sets of amino acid properties. The results suggest that the choice of a proper set of features characterising the protein interface is crucial for the interface prediction task, and that optimality strongly depends on the class of proteins whose interface we want to characterise. We postulate that different protein classes should be treated separately and that it is necessary to identify an optimal set of features for each protein class.}, } @article {pmid29409445, year = {2018}, author = {Namous, H and Peñagaricano, F and Del Corvo, M and Capra, E and Thomas, DL and Stella, A and Williams, JL and Marsan, PA and Khatib, H}, title = {Integrative analysis of methylomic and transcriptomic data in fetal sheep muscle tissues in response to maternal diet during pregnancy.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {123}, pmid = {29409445}, issn = {1471-2164}, support = {AAA3936//College of Agricultural and Life Sciences/International ; }, mesh = {Animals ; Computational Biology/methods ; *DNA Methylation ; *Diet ; *Epigenesis, Genetic ; Female ; Fetus/*metabolism ; Gene Expression Regulation ; Genome ; Linkage Disequilibrium ; *Maternal Exposure ; Muscles/*metabolism ; Pregnancy ; Reproducibility of Results ; Sequence Analysis, DNA ; Sheep/embryology/*genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Numerous studies have established a link between maternal diet and the physiological and metabolic phenotypes of their offspring. In previous studies in sheep, we demonstrated that different maternal diets altered the transcriptome of fetal tissues. However, the mechanisms underlying transcriptomic changes are poorly understood. DNA methylation is an epigenetic mark regulating transcription and is largely influenced by dietary components of the one-carbon cycle that generate the methyl group donor, SAM. Therefore, in the present study, we tested whether different maternal diets during pregnancy would alter the DNA methylation and gene expression patterns in fetal tissues.

RESULTS: Pregnant ewes were randomly divided into two groups which received either hay or corn diet from mid-gestation (day 67 ± 5) until day 131 ± 1 when fetuses were collected by necropsy. A total of 1516 fetal longissimus dorsi (LD) tissues were used for DNA methylation analysis and gene expression profiling. Whole genome DNA methylation using methyl-binding domain enrichment analysis revealed 60 differentially methylated regions (DMRs) between hay and corn fetuses with 39 DMRs more highly methylated in the hay fetuses vs. 21 DMRs more highly methylated in the corn fetuses. Three DMRs (LPAR3, PLIN5-PLIN4, and the differential methylation of a novel lincRNA) were validated using bisulfite sequencing. These DMRs were associated with differential gene expression. Additionally, significant DNA methylation differences were found at the single CpG level. Integrative methylome and transcriptome analysis revealed an association between gene expression and inter-/intragenic methylated regions. Furthermore, intragenic DMRs were found to be associated with expression of neighboring genes.

CONCLUSIONS: The findings of this study imply that maternal diet from mid- to late-gestation can shape the epigenome and the transcriptome of fetal tissues, and putatively affect phenotypes of the lambs.}, } @article {pmid29409442, year = {2018}, author = {Kilicoglu, H and Ben Abacha, A and Mrabet, Y and Shooshan, SE and Rodriguez, L and Masterton, K and Demner-Fushman, D}, title = {Semantic annotation of consumer health questions.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {34}, pmid = {29409442}, issn = {1471-2105}, support = {Intramural Program//U.S. National Library of Medicine (US)/International ; }, mesh = {Electronic Mail ; *Health Status ; Humans ; Semantics ; *Surveys and Questionnaires ; Web Browser ; }, abstract = {BACKGROUND: Consumers increasingly use online resources for their health information needs. While current search engines can address these needs to some extent, they generally do not take into account that most health information needs are complex and can only fully be expressed in natural language. Consumer health question answering (QA) systems aim to fill this gap. A major challenge in developing consumer health QA systems is extracting relevant semantic content from the natural language questions (question understanding). To develop effective question understanding tools, question corpora semantically annotated for relevant question elements are needed. In this paper, we present a two-part consumer health question corpus annotated with several semantic categories: named entities, question triggers/types, question frames, and question topic. The first part (CHQA-email) consists of relatively long email requests received by the U.S. National Library of Medicine (NLM) customer service, while the second part (CHQA-web) consists of shorter questions posed to MedlinePlus search engine as queries. Each question has been annotated by two annotators. The annotation methodology is largely the same between the two parts of the corpus; however, we also explain and justify the differences between them. Additionally, we provide information about corpus characteristics, inter-annotator agreement, and our attempts to measure annotation confidence in the absence of adjudication of annotations.

RESULTS: The resulting corpus consists of 2614 questions (CHQA-email: 1740, CHQA-web: 874). Problems are the most frequent named entities, while treatment and general information questions are the most common question types. Inter-annotator agreement was generally modest: question types and topics yielded highest agreement, while the agreement for more complex frame annotations was lower. Agreement in CHQA-web was consistently higher than that in CHQA-email. Pairwise inter-annotator agreement proved most useful in estimating annotation confidence.

CONCLUSIONS: To our knowledge, our corpus is the first focusing on annotation of uncurated consumer health questions. It is currently used to develop machine learning-based methods for question understanding. We make the corpus publicly available to stimulate further research on consumer health QA.}, } @article {pmid29409441, year = {2018}, author = {Di Salvo, M and Pinatel, E and Talà, A and Fondi, M and Peano, C and Alifano, P}, title = {G4PromFinder: an algorithm for predicting transcription promoters in GC-rich bacterial genomes based on AT-rich elements and G-quadruplex motifs.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {36}, pmid = {29409441}, issn = {1471-2105}, mesh = {*Algorithms ; Bacteria/*genetics ; G-Quadruplexes ; *Genome, Bacterial ; Nucleotide Motifs ; *Promoter Regions, Genetic ; Pseudomonas aeruginosa/genetics ; Streptomyces coelicolor/genetics ; }, abstract = {BACKGROUND: Over the last few decades, computational genomics has tremendously contributed to decipher biology from genome sequences and related data. Considerable effort has been devoted to the prediction of transcription promoter and terminator sites that represent the essential "punctuation marks" for DNA transcription. Computational prediction of promoters in prokaryotes is a problem whose solution is far from being determined in computational genomics. The majority of published bacterial promoter prediction tools are based on a consensus-sequences search and they were designed specifically for vegetative σ70 promoters and, therefore, not suitable for promoter prediction in bacteria encoding a lot of σ factors, like actinomycetes.

RESULTS: In this study we investigated the possibility to identify putative promoters in prokaryotes based on evolutionarily conserved motifs, and focused our attention on GC-rich bacteria in which promoter prediction with conventional, consensus-based algorithms is often not-exhaustive. Here, we introduce G4PromFinder, a novel algorithm that predicts putative promoters based on AT-rich elements and G-quadruplex DNA motifs. We tested its performances by using available genomic and transcriptomic data of the model microorganisms Streptomyces coelicolor A3(2) and Pseudomonas aeruginosa PA14. We compared our results with those obtained by three currently available promoter predicting algorithms: the σ70consensus-based PePPER, the σ factors consensus-based bTSSfinder, and PromPredict which is based on double-helix DNA stability. Our results demonstrated that G4PromFinder is more suitable than the three reference tools for both the genomes. In fact our algorithm achieved the higher accuracy (F1-scores 0.61 and 0.53 in the two genomes) as compared to the next best tool that is PromPredict (F1-scores 0.46 and 0.48). Consensus-based algorithms produced lower performances with the analyzed GC-rich genomes.

CONCLUSIONS: Our analysis shows that G4PromFinder is a powerful tool for promoter search in GC-rich bacteria, especially for bacteria coding for a lot of σ factors, such as the model microorganism S. coelicolor A3(2). Moreover consensus-based tools and, in general, tools that are based on specific features of bacterial σ factors seem to be less performing for promoter prediction in these types of bacterial genomes.}, } @article {pmid29409440, year = {2018}, author = {Reaney, AM and Saldarriaga-Córdoba, M and Pincheira-Donoso, D}, title = {Macroevolutionary diversification with limited niche disparity in a species-rich lineage of cold-climate lizards.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {16}, pmid = {29409440}, issn = {1471-2148}, mesh = {Animals ; Body Size ; *Climate ; *Ecosystem ; Lizards/anatomy & histology/*classification ; Models, Biological ; *Phylogeny ; South America ; Species Specificity ; }, abstract = {BACKGROUND: Life diversifies via adaptive radiation when natural selection drives the evolution of ecologically distinct species mediated by their access to novel niche space, or via non-adaptive radiation when new species diversify while retaining ancestral niches. However, while cases of adaptive radiation are widely documented, examples of non-adaptively radiating lineages remain rarely observed. A prolific cold-climate lizard radiation from South America (Phymaturus), sister to a hyper-diverse adaptive radiation (Liolaemus), has extensively diversified phylogenetically and geographically, but with exceptionally minimal ecological and life-history diversification. This lineage, therefore, may offer unique opportunities to investigate the non-adaptive basis of diversification, and in combination with Liolaemus, to cover the whole spectrum of modes of diversification predicted by theory, from adaptive to non-adaptive. Using phylogenetic macroevolutionary modelling performed on a newly created 58-species molecular tree, we establish the tempo and mode of diversification in the Phymaturus radiation.

RESULTS: Lineage accumulation in Phymaturus opposes a density-dependent (or 'niche-filling') process of diversification. Concurrently, we found that body size diversification is better described by an Ornstein-Uhlenbeck evolutionary model, suggesting stabilizing selection as the mechanism underlying niche conservatism (i.e., maintaining two fundamental size peaks), and which has predominantly evolved around two major adaptive peaks on a 'Simpsonian' adaptive landscape.

CONCLUSIONS: Lineage diversification of the Phymaturus genus does not conform to an adaptive radiation, as it is characterised by a constant rate of species accumulation during the clade's history. Their strict habitat requirements (rocky outcrops), predominantly invariant herbivory, and especially the constant viviparous reproduction across species have likely limited their opportunities for adaptive diversifications throughout novel environments. This mode of diversification contrasts dramatically with its sister lineage Liolaemus, which geographically overlaps with Phymaturus, but exploits all possible microhabitats in these and other bioclimatic areas. Our study contributes importantly to consolidate these lizards (liolaemids) as promising model systems to investigate the entire spectrum of modes of species formations, from the adaptive to the non-adaptive extremes of the continuum.}, } @article {pmid29408815, year = {2018}, author = {Kourime, M and Ahmed, SF}, title = {Virtual Networks for Exchanging Information and Biomaterials: Future Directions.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {140-144}, doi = {10.1159/000486872}, pmid = {29408815}, issn = {1661-5433}, support = {G1100236//Medical Research Council/United Kingdom ; }, mesh = {Biocompatible Materials/*chemistry ; Disorders of Sex Development/pathology ; Humans ; Internationality ; Registries ; *User-Computer Interface ; }, abstract = {Clinical and research networks for rare conditions are increasingly common nowadays. Given the rarity of many such conditions, there is a need to cover more conditions, yet there is also a need to sustain and improve the quality and effectiveness of existing networks. This review will discuss the qualities that are required by a virtual network using some international clinical and research networks that are currently active in the field of rare endocrine conditions affecting sex and adrenal development as exemplars.}, } @article {pmid29408469, year = {2018}, author = {Kuratani, S and Kusakabe, R and Hirasawa, T}, title = {The neural crest and evolution of the head/trunk interface in vertebrates.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.01.017}, pmid = {29408469}, issn = {1095-564X}, abstract = {The migration and distribution patterns of neural crest (NC) cells reflect the distinct embryonic environments of the head and trunk: cephalic NC cells migrate predominantly along the dorsolateral pathway to populate the craniofacial and pharyngeal regions, whereas trunk crest cells migrate along the ventrolateral pathways to form the dorsal root ganglia. These two patterns thus reflect the branchiomeric and somitomeric architecture, respectively, of the vertebrate body plan. The so-called vagal NC occupies a postotic, intermediate level between the head and trunk NC. This level of NC gives rise to both trunk- and cephalic-type (circumpharyngeal) NC cells. The anatomical pattern of the amphioxus, a basal chordate, suggests that somites and pharyngeal gills coexist along an extensive length of the body axis, indicating that the embryonic environment is similar to that of vertebrate vagal NC cells and may have been ancestral for vertebrates. The amniote-like condition in which the cephalic and trunk domains are distinctly separated would have been brought about, in part, by anteroposterior reduction of the pharyngeal domain.}, } @article {pmid29408286, year = {2018}, author = {Yuan, ML and Zhang, QL and Zhang, L and Jia, CL and Li, XP and Yang, XZ and Feng, RQ}, title = {Mitochondrial phylogeny, divergence history and high-altitude adaptation of grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) inhabiting the Tibetan Plateau.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {116-124}, doi = {10.1016/j.ympev.2018.01.016}, pmid = {29408286}, issn = {1095-9513}, mesh = {*Adaptation, Physiological/genetics ; *Altitude ; Animals ; Biodiversity ; DNA/chemistry/isolation & purification/metabolism ; Grassland ; Mitochondria/*genetics ; Moths/*classification/genetics ; Open Reading Frames/genetics ; *Phylogeny ; Sequence Analysis, DNA ; Tibet ; }, abstract = {Grassland caterpillars (Lepidoptera: Lymantriinae: Gynaephora) are the most important pests in alpine meadows of the Tibetan Plateau (TP) and have well adapted to high-altitude environments. To further understand the evolutionary history and their adaptation to the TP, we newly determined seven complete TP Gynaephora mitogenomes. Compared to single genes, whole mitogenomes provided the best phylogenetic signals and obtained robust results, supporting the monophyly of the TP Gynaephora species and a phylogeny of Arctiinae + (Aganainae + Lymantriinae). Incongruent phylogenetic signals were found among single mitochondrial genes, none of which recovered the same phylogeny as the whole mitogenome. We identified six best-performing single genes using Shimodaira-Hasegawa tests and found that the combinations of rrnS and either cox1 or cox3 generated the same phylogeny as the whole mitogenome, indicating the phylogenetic potential of these three genes for future evolutionary studies of Gynaephora. The TP Gynaephora species were estimated to radiate on the TP during the Pliocene and Quaternary, supporting an association of the diversification and speciation of the TP Gynaephora species with the TP uplifts and associated climate changes during this time. Selection analyses revealed accelerated evolutionary rates of the mitochondrial protein-coding genes in the TP Gynaephora species, suggesting that they accumulated more nonsynonymous substitutions that may benefit their adaptation to high altitudes. Furthermore, signals of positive selection were detected in nad5 of two Gynaephora species with the highest altitude-distributions, indicating that this gene may contribute to Gynaephora's adaptation to divergent altitudes. This study adds to the understanding of the TP Gynaephora evolutionary relationships and suggests a link between mitogenome evolution and ecological adaptation to high-altitude environments in grassland caterpillars.}, } @article {pmid29407482, year = {2018}, author = {Ortiz-Rodriguez, AE and Ornelas, JF and Ruiz-Sanchez, E}, title = {A jungle tale: Molecular phylogeny and divergence time estimates of the Desmopsis-Stenanona clade (Annonaceae) in Mesoamerica.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {80-94}, doi = {10.1016/j.ympev.2018.01.021}, pmid = {29407482}, issn = {1095-9513}, mesh = {Annonaceae/*classification/genetics ; Bayes Theorem ; Biological Evolution ; Cell Nucleus/genetics ; Central America ; Climate ; DNA, Plant/chemistry/isolation & purification/metabolism ; Forests ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The predominantly Asian tribe Miliuseae (Annonaceae) includes over 37 Neotropical species that are mainly distributed across Mesoamerica, from southern Mexico to northern Colombia. The tremendous ecological and morphological diversity of this clade, including ramiflory, cauliflory, flagelliflory, and clonality, suggests adaptive radiation. Despite the spectacular phenotypic divergence of this clade, little is known about its phylogenetic and evolutionary history. In this study we used a nuclear DNA marker and seven chloroplast markers, and maximum parsimony, maximum likelihood and Bayesian inference methods to reconstruct a comprehensive time-calibrated phylogeny of tribe Miliuseae, especially focusing on the Desmopsis-Stenanona clade. We also perform ancestral area reconstructions to infer the biogeographic history of this group. Finally, we use ecological niche modeling, lineage distribution models, and niche overlap tests to assess whether geographic isolation and ecological specialization influenced the diversification of lineages within this clade. We reconstructed a monophyletic Miliuseae that is divided into two strongly supported clades: (i) a Sapranthus-Tridimeris clade and (ii) a Desmopsis-Stenanona clade. The colonization of the Neotropics and subsequent diversification of Neotropical Miliuseae seems to have been associated with the expansion of the boreotropical forests during the late Eocene and their subsequent fragmentation and southern displacement. Further speciation within Neotropical Miliuseae out of the Maya block seems to have occurred during the last 15 million years. Lastly, the geographic structuring of major lineages of the Desmopsis-Stenanona clade seems to have followed a climatic gradient, supporting the hypothesis that morphological differentiation between closely related species resulted from both long-term isolation between geographic ranges and adaptation to environmental conditions.}, } @article {pmid29407481, year = {2018}, author = {Goloboff, PA and Wilkinson, M}, title = {On defining a unique phylogenetic tree with homoplastic characters.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {95-101}, doi = {10.1016/j.ympev.2018.01.020}, pmid = {29407481}, issn = {1095-9513}, mesh = {*Algorithms ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {This paper discusses the problem of whether creating a matrix with all the character state combinations that have a fixed number of steps (or extra steps) on a given tree T, produces the same tree T when analyzed with maximum parsimony or maximum likelihood. Exhaustive enumeration of cases up to 20 taxa for binary characters, and up to 12 taxa for 4-state characters, shows that the same tree is recovered (as unique most likely or most parsimonious tree) as long as the number of extra steps is within 1/4 of the number of taxa. This dependence, 1/4 of the number of taxa, is discussed with a general argumentation, in terms of the spread of the character changes on the tree used to select character state distributions. The present finding allows creating matrices which have as much homoplasy as possible for the most parsimonious or likely tree to be predictable, and examination of these matrices with hill-climbing search algorithms provides additional evidence on the (lack of a) necessary relationship between homoplasy and the ability of search methods to find optimal trees.}, } @article {pmid29407045, year = {2018}, author = {Bogdanova, K and Röderova, M and Kolar, M and Langova, K and Dusek, M and Jost, P and Kubelkova, K and Bostik, P and Olsovska, J}, title = {Antibiofilm activity of bioactive hop compounds humulone, lupulone and xanthohumol toward susceptible and resistant staphylococci.}, journal = {Research in microbiology}, volume = {169}, number = {3}, pages = {127-134}, doi = {10.1016/j.resmic.2017.12.005}, pmid = {29407045}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/*pharmacology ; Biofilms/*drug effects ; Cell Line ; Cell Survival/drug effects ; Cyclohexenes/*pharmacology ; Flavonoids/*pharmacology ; Humans ; Humulus/chemistry ; Microbial Sensitivity Tests ; Plant Extracts/pharmacology ; Propiophenones/*pharmacology ; Staphylococcus/*drug effects/genetics/*growth & development ; Terpenes/*pharmacology ; }, abstract = {Bacterial biofilms pose a serious medical problem due to their significant resistance to antimicrobials, and staphylococci are recognized as the most frequent cause of biofilm-associated infections. The hop plant (Humulus lupulus L.) contains substances that have been determined to act as anti-infective agents against bacteria, mainly in planktonic form. Therefore, we decided to investigate the antibiofilm properties of H. lupulus L.-derived compounds (humulone, lupulone and xanthohumol) against a selected group of Staphylococcus spp., including methicillin-susceptible and resistant strains. All tested hop compounds were shown to possess antimicrobial properties against all tested staphylococci, both planktonic and biofilm-dwelling, with no significant difference between resistant and susceptible strains. All compounds lowered the number of bacterial cells released from the biofilm, with the strongest effect seen for lupulone, followed by xanthohumol. Moreover, lupulone and xanthohumol were not only able to penetrate the biofilm and reduce the number of bacteria within it, but their higher concentrations (∼60 μg/mL for xanthohumol and ∼125 μg/mL for lupulone) reduced the number of surviving bacterial cells to zero.}, } @article {pmid29407044, year = {2018}, author = {Vargiu, AV and Ramaswamy, VK and Malloci, G and Malvacio, I and Atzori, A and Ruggerone, P}, title = {Computer simulations of the activity of RND efflux pumps.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {384-392}, doi = {10.1016/j.resmic.2017.12.001}, pmid = {29407044}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/*metabolism ; Bacteria/chemistry/genetics/*metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; *Computer Simulation ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; }, abstract = {The putative mechanism by which bacterial RND-type multidrug efflux pumps recognize and transport their substrates is a complex and fascinating enigma of structural biology. How a single protein can recognize a huge number of unrelated compounds and transport them through one or just a few mechanisms is an amazing feature not yet completely unveiled. The appearance of cooperativity further complicates the understanding of structure-dynamics-activity relationships in these complex machineries. Experimental techniques may have limited access to the molecular determinants and to the energetics of key processes regulating the activity of these pumps. Computer simulations are a complementary approach that can help unveil these features and inspire new experiments. Here we review recent computational studies that addressed the various molecular processes regulating the activity of RND efflux pumps.}, } @article {pmid29403079, year = {2018}, author = {O'Donovan, C and Meade, A and Venditti, C}, title = {Dinosaurs reveal the geographical signature of an evolutionary radiation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {452-458}, doi = {10.1038/s41559-017-0454-6}, pmid = {29403079}, issn = {2397-334X}, abstract = {Dinosaurs dominated terrestrial ecosystems across the globe for over 100 million years and provide a classic example of an evolutionary radiation. However, little is known about how these animals radiated geographically to become globally distributed. Here, we use a biogeographical model to reconstruct the dinosaurs' ancestral locations, revealing the spatial mechanisms that underpinned this 170-million-year-long radiation. We find that dinosaurs spread rapidly initially, followed by a significant continuous and gradual reduction in their speed of movement towards the Cretaceous/Tertiary boundary (66 million years ago). This suggests that the predominant mode of dinosaur speciation changed through time with speciation originally largely driven by geographical isolation-when dinosaurs speciated more, they moved further. This was gradually replaced by increasing levels of sympatric speciation (species taking advantage of ecological opportunities within their existing environment) as terrestrial space became a limiting factor. Our results uncover the geographical signature of an evolutionary radiation.}, } @article {pmid29403078, year = {2018}, author = {Organ, C}, title = {Biogeography across the ages.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {412-413}, doi = {10.1038/s41559-018-0486-6}, pmid = {29403078}, issn = {2397-334X}, } @article {pmid29403077, year = {2018}, author = {Tulloch, AIT and Chadès, I and Lindenmayer, DB}, title = {Species co-occurrence analysis predicts management outcomes for multiple threats.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {465-474}, doi = {10.1038/s41559-017-0457-3}, pmid = {29403077}, issn = {2397-334X}, abstract = {Mitigating the impacts of global anthropogenic change on species is conservation's greatest challenge. Forecasting the effects of actions to mitigate threats is hampered by incomplete information on species' responses. We develop an approach to predict community restructuring under threat management, which combines models of responses to threats with network analyses of species co-occurrence. We discover that contributions by species to network co-occurrence predict their recovery under reduction of multiple threats. Highly connected species are likely to benefit more from threat management than poorly connected species. Importantly, we show that information from a few species on co-occurrence and expected responses to alternative threat management actions can be used to train a response model for an entire community. We use a unique management dataset for a threatened bird community to validate our predictions and, in doing so, demonstrate positive feedbacks in occurrence and co-occurrence resulting from shared threat management responses during ecosystem recovery.}, } @article {pmid29403076, year = {2018}, author = {Huang, D and Hormiga, G and Cai, C and Su, Y and Yin, Z and Xia, F and Giribet, G}, title = {Origin of spiders and their spinning organs illuminated by mid-Cretaceous amber fossils.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {623-627}, doi = {10.1038/s41559-018-0475-9}, pmid = {29403076}, issn = {2397-334X}, abstract = {Understanding the genealogical relationships among the arachnid orders is an onerous task, but fossils have aided in anchoring some branches of the arachnid tree of life. The discovery of Palaeozoic fossils with characters found in both extant spiders and other arachnids provided evidence for a series of extinctions of what was thought to be a grade, Uraraneida, that led to modern spiders. Here, we report two extraordinarily well-preserved Mesozoic members of Uraraneida with a segmented abdomen, multi-articulate spinnerets with well-defined spigots, modified male palps, spider-like chelicerae and a uropygid-like telson. The new fossils, belonging to the species Chimerarachne yingi, were analysed phylogenetically in a large data matrix of extant and extinct arachnids under a diverse regime of analytical conditions, most of which resulted in placing Uraraneida as the sister clade of Araneae (spiders). The phylogenetic placement of this arachnid fossil extends the presence of spinnerets and modified palps more basally in the arachnid tree than was previously thought. Ecologically, the new fossil extends the record of Uraraneida 170 million years towards the present, thus showing that uraraneids and spiders co-existed for a large fraction of their evolutionary history.}, } @article {pmid29403075, year = {2018}, author = {Wang, B and Dunlop, JA and Selden, PA and Garwood, RJ and Shear, WA and Müller, P and Lei, X}, title = {Cretaceous arachnid Chimerarachne yingi gen. et sp. nov. illuminates spider origins.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {614-622}, doi = {10.1038/s41559-017-0449-3}, pmid = {29403075}, issn = {2397-334X}, abstract = {Spiders (Araneae) are a hugely successful lineage with a long history. Details of their origins remain obscure, with little knowledge of their stem group and few insights into the sequence of character acquisition during spider evolution. Here, we describe Chimerarachne yingi gen. et sp. nov., a remarkable arachnid from the mid-Cretaceous (approximately 100 million years ago) Burmese amber of Myanmar, which documents a key transition stage in spider evolution. Like uraraneids, the two fossils available retain a segmented opisthosoma bearing a whip-like telson, but also preserve two traditional synapomorphies for Araneae: a male pedipalp modified for sperm transfer and well-defined spinnerets resembling those of modern mesothele spiders. This unique character combination resolves C. yingi within a clade including both Araneae and Uraraneida; however, its exact position relative to these orders is sensitive to different parameters of our phylogenetic analysis. Our new fossil most likely represents the earliest branch of the Araneae, and implies that there was a lineage of tailed spiders that presumably originated in the Palaeozoic and survived at least into the Cretaceous of Southeast Asia.}, } @article {pmid29403074, year = {2018}, author = {Harrison, MC and Jongepier, E and Robertson, HM and Arning, N and Bitard-Feildel, T and Chao, H and Childers, CP and Dinh, H and Doddapaneni, H and Dugan, S and Gowin, J and Greiner, C and Han, Y and Hu, H and Hughes, DST and Huylmans, AK and Kemena, C and Kremer, LPM and Lee, SL and Lopez-Ezquerra, A and Mallet, L and Monroy-Kuhn, JM and Moser, A and Murali, SC and Muzny, DM and Otani, S and Piulachs, MD and Poelchau, M and Qu, J and Schaub, F and Wada-Katsumata, A and Worley, KC and Xie, Q and Ylla, G and Poulsen, M and Gibbs, RA and Schal, C and Richards, S and Belles, X and Korb, J and Bornberg-Bauer, E}, title = {Hemimetabolous genomes reveal molecular basis of termite eusociality.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {557-566}, doi = {10.1038/s41559-017-0459-1}, pmid = {29403074}, issn = {2397-334X}, support = {U54 HG003273/HG/NHGRI NIH HHS/United States ; }, abstract = {Around 150 million years ago, eusocial termites evolved from within the cockroaches, 50 million years before eusocial Hymenoptera, such as bees and ants, appeared. Here, we report the 2-Gb genome of the German cockroach, Blattella germanica, and the 1.3-Gb genome of the drywood termite Cryptotermes secundus. We show evolutionary signatures of termite eusociality by comparing the genomes and transcriptomes of three termites and the cockroach against the background of 16 other eusocial and non-eusocial insects. Dramatic adaptive changes in genes underlying the production and perception of pheromones confirm the importance of chemical communication in the termites. These are accompanied by major changes in gene regulation and the molecular evolution of caste determination. Many of these results parallel molecular mechanisms of eusocial evolution in Hymenoptera. However, the specific solutions are remarkably different, thus revealing a striking case of convergence in one of the major evolutionary transitions in biological complexity.}, } @article {pmid29403073, year = {2018}, author = {Higgs, ES and Harris, JA and Heger, T and Hobbs, RJ and Murphy, SD and Suding, KN}, title = {Keep ecological restoration open and flexible.}, journal = {Nature ecology & evolution}, volume = {2}, number = {4}, pages = {580}, doi = {10.1038/s41559-018-0483-9}, pmid = {29403073}, issn = {2397-334X}, } @article {pmid29403072, year = {2018}, author = {Gutekunst, J and Andriantsoa, R and Falckenhayn, C and Hanna, K and Stein, W and Rasamy, J and Lyko, F}, title = {Clonal genome evolution and rapid invasive spread of the marbled crayfish.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {567-573}, doi = {10.1038/s41559-018-0467-9}, pmid = {29403072}, issn = {2397-334X}, abstract = {The marbled crayfish Procambarus virginalis is a unique freshwater crayfish characterized by very recent speciation and parthenogenetic reproduction. Marbled crayfish also represent an emerging invasive species and have formed wild populations in diverse freshwater habitats. However, our understanding of marbled crayfish biology, evolution and invasive spread has been hampered by the lack of freshwater crayfish genome sequences. We have now established a de novo draft assembly of the marbled crayfish genome. We determined the genome size at approximately 3.5 gigabase pairs and identified >21,000 genes. Further analysis confirmed the close relationship to the genome of the slough crayfish, Procambarus fallax, and also established a triploid AA'B genotype with a high level of heterozygosity. Systematic fieldwork and genotyping demonstrated the rapid expansion of marbled crayfish on Madagascar and established the marbled crayfish as a potent invader of freshwater ecosystems. Furthermore, comparative whole-genome sequencing demonstrated the clonality of the population and their genetic identity with the oldest known stock from the German aquarium trade. Our study closes an important gap in the phylogenetic analysis of animal genomes and uncovers the unique evolutionary history of an emerging invasive species.}, } @article {pmid29403015, year = {2018}, author = {Dortet, L and Lombardi, C and Cretin, F and Dessen, A and Filloux, A}, title = {Pore-forming activity of the Pseudomonas aeruginosa type III secretion system translocon alters the host epigenome.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {378-386}, doi = {10.1038/s41564-018-0109-7}, pmid = {29403015}, issn = {2058-5276}, support = {MR/K001930/1//Medical Research Council/United Kingdom ; }, abstract = {Recent studies highlight that bacterial pathogens can reprogram target cells by influencing epigenetic factors. The type III secretion system (T3SS) is a bacterial nanomachine that resembles a syringe on the bacterial surface. The T3SS 'needle' delivers translocon proteins into eukaryotic cell membranes, subsequently allowing injection of bacterial effectors into the cytosol. Here we show that Pseudomonas aeruginosa induces early T3SS-dependent dephosphorylation and deacetylation of histone H3 in eukaryotic cells. This is not triggered by any of the P. aeruginosa T3SS effectors, but results from the insertion of the PopB-PopD translocon into the membrane. This suggests that the P. aeruginosa translocon is a genuine T3SS effector acting as a pore-forming toxin. We visualized the translocon plugged into the host cell membrane after the bacterium has left the site of contact, and demonstrate that subsequent ion exchange through this pore is responsible for histone H3 modifications and host cell subversion.}, } @article {pmid29403014, year = {2018}, author = {Banno, S and Nishida, K and Arazoe, T and Mitsunobu, H and Kondo, A}, title = {Deaminase-mediated multiplex genome editing in Escherichia coli.}, journal = {Nature microbiology}, volume = {3}, number = {4}, pages = {423-429}, doi = {10.1038/s41564-017-0102-6}, pmid = {29403014}, issn = {2058-5276}, abstract = {In eukaryotes, the CRISPR-Cas9 system has now been widely used as a revolutionary genome engineering tool1, 2. However, in prokaryotes, the use of nuclease-mediated genome editing tools has been limited to negative selection for the already modified cells because of its lethality3, 4. Here, we report on deaminase-mediated targeted nucleotide editing (Target-AID) 5 adopted in Escherichia coli. Cytidine deaminase PmCDA1 fused to the nuclease-deficient CRISPR-Cas9 system achieved specific point mutagenesis at the target sites in E. coli by introducing cytosine mutations without compromising cell growth. The cytosine-to-thymine substitutions were induced mainly within an approximately five-base window of target sequences on the protospacer adjacent motif-distal side, which can be shifted depending on the length of the single guide RNA sequence. Use of a uracil DNA glycosylase inhibitor 6 in combination with a degradation tag (LVA tag) 7 resulted in a robustly high mutation efficiency, which allowed simultaneous multiplex editing of six different genes. The major multi-copy transposase genes that consist of at least 41 loci were also simultaneously edited by using four target sequences. As this system does not rely on any additional or host-dependent factors, it may be readily applicable to a wide range of bacteria.}, } @article {pmid29403013, year = {2018}, author = {Behler, J and Sharma, K and Reimann, V and Wilde, A and Urlaub, H and Hess, WR}, title = {The host-encoded RNase E endonuclease as the crRNA maturation enzyme in a CRISPR-Cas subtype III-Bv system.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {367-377}, doi = {10.1038/s41564-017-0103-5}, pmid = {29403013}, issn = {2058-5276}, abstract = {Specialized RNA endonucleases for the maturation of clustered regularly interspaced short palindromic repeat (CRISPR)-derived RNAs (crRNAs) are critical in CRISPR-CRISPR-associated protein (Cas) defence mechanisms. The Cas6 and Cas5d enzymes are the RNA endonucleases in many class 1 CRISPR-Cas systems. In some class 2 systems, maturation and effector functions are combined within a single enzyme or maturation proceeds through the combined actions of RNase III and trans-activating CRISPR RNAs (tracrRNAs). Three separate CRISPR-Cas systems exist in the cyanobacterium Synechocystis sp. PCC 6803. Whereas Cas6-type enzymes act in two of these systems, the third, which is classified as subtype III-B variant (III-Bv), lacks cas6 homologues. Instead, the maturation of crRNAs proceeds through the activity of endoribonuclease E, leaving unusual 13- and 14-nucleotide-long 5'-handles. Overexpression of RNase E leads to overaccumulation and knock-down to the reduced accumulation of crRNAs in vivo, suggesting that RNase E is the limiting factor for CRISPR complex formation. Recognition by RNase E depends on a stem-loop in the CRISPR repeat, whereas base substitutions at the cleavage site trigger the appearance of secondary products, consistent with a two-step recognition and cleavage mechanism. These results suggest the adaptation of an otherwise very conserved housekeeping enzyme to accommodate new substrates and illuminate the impressive plasticity of CRISPR-Cas systems that enables them to function in particular genomic environments.}, } @article {pmid29403012, year = {2018}, author = {Fernandes-Rosa, FL and Daniil, G and Orozco, IJ and Göppner, C and El Zein, R and Jain, V and Boulkroun, S and Jeunemaitre, X and Amar, L and Lefebvre, H and Schwarzmayr, T and Strom, TM and Jentsch, TJ and Zennaro, MC}, title = {A gain-of-function mutation in the CLCN2 chloride channel gene causes primary aldosteronism.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {355-361}, doi = {10.1038/s41588-018-0053-8}, pmid = {29403012}, issn = {1546-1718}, abstract = {Primary aldosteronism is the most common and curable form of secondary arterial hypertension. We performed whole-exome sequencing in patients with early-onset primary aldosteronism and identified a de novo heterozygous c.71G>A/p.Gly24Asp mutation in the CLCN2 gene, encoding the voltage-gated ClC-2 chloride channel 1 , in a patient diagnosed at 9 years of age. Patch-clamp analysis of glomerulosa cells of mouse adrenal gland slices showed hyperpolarization-activated Cl- currents that were abolished in Clcn2-/- mice. The p.Gly24Asp variant, located in a well-conserved 'inactivation domain'2,3, abolished the voltage- and time-dependent gating of ClC-2 and strongly increased Cl- conductance at resting potentials. Expression of ClC-2Asp24 in adrenocortical cells increased expression of aldosterone synthase and aldosterone production. Our data indicate that CLCN2 mutations cause primary aldosteronism. They highlight the important role of chloride in aldosterone biosynthesis and identify ClC-2 as the foremost chloride conductor of resting glomerulosa cells.}, } @article {pmid29403011, year = {2018}, author = {Scholl, UI and Stölting, G and Schewe, J and Thiel, A and Tan, H and Nelson-Williams, C and Vichot, AA and Jin, SC and Loring, E and Untiet, V and Yoo, T and Choi, J and Xu, S and Wu, A and Kirchner, M and Mertins, P and Rump, LC and Onder, AM and Gamble, C and McKenney, D and Lash, RW and Jones, DP and Chune, G and Gagliardi, P and Choi, M and Gordon, R and Stowasser, M and Fahlke, C and Lifton, RP}, title = {CLCN2 chloride channel mutations in familial hyperaldosteronism type II.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {349-354}, pmid = {29403011}, issn = {1546-1718}, support = {UM1 HG006504/HG/NHGRI NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; S10 OD018521/OD/NIH HHS/United States ; U54 HG006504/HG/NHGRI NIH HHS/United States ; P01 DK017433/DK/NIDDK NIH HHS/United States ; }, abstract = {Primary aldosteronism, a common cause of severe hypertension 1 , features constitutive production of the adrenal steroid aldosterone. We analyzed a multiplex family with familial hyperaldosteronism type II (FH-II) 2 and 80 additional probands with unsolved early-onset primary aldosteronism. Eight probands had novel heterozygous variants in CLCN2, including two de novo mutations and four independent occurrences of a mutation encoding an identical p.Arg172Gln substitution; all relatives with early-onset primary aldosteronism carried the CLCN2 variant found in the proband. CLCN2 encodes a voltage-gated chloride channel expressed in adrenal glomerulosa that opens at hyperpolarized membrane potentials. Channel opening depolarizes glomerulosa cells and induces expression of aldosterone synthase, the rate-limiting enzyme for aldosterone biosynthesis. Mutant channels show gain of function, with higher open probabilities at the glomerulosa resting potential. These findings for the first time demonstrate a role of anion channels in glomerulosa membrane potential determination, aldosterone production and hypertension. They establish the cause of a substantial fraction of early-onset primary aldosteronism.}, } @article {pmid29403010, year = {2018}, author = {Kanai, M and Akiyama, M and Takahashi, A and Matoba, N and Momozawa, Y and Ikeda, M and Iwata, N and Ikegawa, S and Hirata, M and Matsuda, K and Kubo, M and Okada, Y and Kamatani, Y}, title = {Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {390-400}, doi = {10.1038/s41588-018-0047-6}, pmid = {29403010}, issn = {1546-1718}, abstract = {Clinical measurements can be viewed as useful intermediate phenotypes to promote understanding of complex human diseases. To acquire comprehensive insights into the underlying genetics, here we conducted a genome-wide association study (GWAS) of 58 quantitative traits in 162,255 Japanese individuals. Overall, we identified 1,407 trait-associated loci (P < 5.0 × 10-8), 679 of which were novel. By incorporating 32 additional GWAS results for complex diseases and traits in Japanese individuals, we further highlighted pleiotropy, genetic correlations, and cell-type specificity across quantitative traits and diseases, which substantially expands the current understanding of the associated genetics and biology. This study identified both shared polygenic effects and cell-type specificity, represented by the genetic links among clinical measurements, complex diseases, and relevant cell types. Our findings demonstrate that even without prior biological knowledge of cross-phenotype relationships, genetics corresponding to clinical measurements successfully recapture those measurements' relevance to diseases, and thus can contribute to the elucidation of unknown etiology and pathogenesis.}, } @article {pmid29402865, year = {2018}, author = {Hiort, O}, title = {Concluding Remarks - From Bench to Bed.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {155-157}, doi = {10.1159/000486880}, pmid = {29402865}, issn = {1661-5433}, mesh = {Disorders of Sex Development/diagnostic imaging/genetics/*pathology/surgery ; Endocrine System/metabolism ; Humans ; *Translational Medical Research ; }, } @article {pmid29402580, year = {2018}, author = {Tapia-Torres, Y and Olmedo-Álvarez, G}, title = {Life on Phosphite: A Metagenomics Tale.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {170-172}, doi = {10.1016/j.tim.2018.01.002}, pmid = {29402580}, issn = {1878-4380}, mesh = {*Metagenomics ; Oxidation-Reduction ; *Phosphites ; Sewage ; }, abstract = {Phosphite, a species of phosphorus in a P3+ oxidation state, is believed to have played an important role in the primordial Earth. Figueroa et al. used metagenomics to uncover anaerobic bacterial communities from waste water waste sludge that sustain life from energy provided by phosphite.}, } @article {pmid29402564, year = {2018}, author = {Benelli, G and Pombi, M and Otranto, D}, title = {Malaria in Italy - Migrants Are Not the Cause.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {351-354}, doi = {10.1016/j.pt.2018.01.002}, pmid = {29402564}, issn = {1471-5007}, mesh = {Humans ; Italy/epidemiology ; Malaria/epidemiology/*transmission ; Risk Factors ; *Transients and Migrants ; }, abstract = {Recently, five cases of malaria were reported in Italy. These people had not travelled abroad, prompting some media and political organizations to fuel a climate of fear by connecting the cases with migrants coming into the country. Here, we discuss scientific data highlighting the limited risk of malaria reintroduction in Italy.}, } @article {pmid29402462, year = {2018}, author = {Godsoe, W and Jankowski, J and Holt, RD and Gravel, D}, title = {Which Coexistence Mechanisms Should Biogeographers Quantify? A Reply to Alexander et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {145-147}, doi = {10.1016/j.tree.2018.01.003}, pmid = {29402462}, issn = {1872-8383}, } @article {pmid29402392, year = {2018}, author = {Liu, C and Moschou, PN}, title = {Phenotypic novelty by CRISPR in plants.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {170-175}, doi = {10.1016/j.ydbio.2018.01.015}, pmid = {29402392}, issn = {1095-564X}, mesh = {Alleles ; *CRISPR-Cas Systems ; DNA Shuffling ; Epigenomics ; Gene Editing/*methods ; Gene Expression Regulation, Plant ; Gene Knockout Techniques ; *Genes, Plant ; INDEL Mutation ; Phenotype ; Plants/*genetics ; *Plants, Genetically Modified ; Ploidies ; Protein Processing, Post-Translational ; Recombinational DNA Repair ; }, abstract = {Genome editing by CRISPR is now routinely used in plant biology for unravelling gene functions and improving agronomical traits. CRISPR opens up the possibility of genome manipulations which would have been unthinkable a few years ago. In this perspective, we discuss and suggest CRISPR-mediated approaches for steering plant development, also highlighting potential challenges.}, } @article {pmid29402334, year = {2018}, author = {McCaul, M and de Waal, B and Hodkinson, P and Pigoga, JL and Young, T and Wallis, LA}, title = {Developing prehospital clinical practice guidelines for resource limited settings: why re-invent the wheel?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {97}, pmid = {29402334}, issn = {1756-0500}, support = {N/A//Health Professions Council of South Africa/ ; 5242//UK aid, Effective Health Care Research Consortium/ ; }, mesh = {Developing Countries ; Emergency Medical Services/*methods ; Evidence-Based Medicine/*methods ; Health Knowledge, Attitudes, Practice ; Humans ; *Practice Guidelines as Topic ; South Africa ; }, abstract = {OBJECTIVES: Methods on developing new (de novo) clinical practice guidelines (CPGs) have received substantial attention. However, the volume of literature is not matched by research into alternative methods of CPG development using existing CPG documents-a specific issue for guideline development groups in low- and middle-income countries. We report on how we developed a context specific prehospital CPG using an alternative guideline development method. Difficulties experienced and lessons learnt in applying existing global guidelines' recommendations to a national context are highlighted.

RESULTS: The project produced the first emergency care CPG for prehospital providers in Africa. It included > 270 CPGs and produced over 1000 recommendations for prehospital emergency care. We encountered various difficulties, including (1) applicability issues: few pre-hospital CPGs applicable to Africa, (2) evidence synthesis: heterogeneous levels of evidence classifications and (3) guideline quality. Learning points included (1) focusing on key CPGs and evidence mapping, (2) searching other resources for CPGs, (3) broad representation on CPG advisory boards and (4) transparency and knowledge translation. Re-inventing the wheel to produce CPGs is not always feasible. We hope this paper will encourage further projects to use existing CPGs in developing guidance to improve patient care in resource-limited settings.}, } @article {pmid29402331, year = {2018}, author = {Shi, Y and Li, Y and Xiang, X and Sun, R and Yang, T and He, D and Zhang, K and Ni, Y and Zhu, YG and Adams, JM and Chu, H}, title = {Spatial scale affects the relative role of stochasticity versus determinism in soil bacterial communities in wheat fields across the North China Plain.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {27}, pmid = {29402331}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics/isolation & purification ; Biodiversity ; China ; High-Throughput Nucleotide Sequencing/*methods ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; Soil Microbiology ; Stochastic Processes ; Triticum/*growth & development ; }, abstract = {BACKGROUND: The relative importance of stochasticity versus determinism in soil bacterial communities is unclear, as are the possible influences that alter the balance between these. Here, we investigated the influence of spatial scale on the relative role of stochasticity and determinism in agricultural monocultures consisting only of wheat, thereby minimizing the influence of differences in plant species cover and in cultivation/disturbance regime, extending across a wide range of soils and climates of the North China Plain (NCP). We sampled 243 sites across 1092 km and sequenced the 16S rRNA bacterial gene using MiSeq. We hypothesized that determinism would play a relatively stronger role at the broadest scales, due to the strong influence of climate and soil differences in selecting many distinct OTUs of bacteria adapted to the different environments. In order to test the more general applicability of the hypothesis, we also compared with a natural ecosystem on the Tibetan Plateau.

RESULTS: Our results revealed that the relative importance of stochasticity vs. determinism did vary with spatial scale, in the direction predicted. On the North China Plain, stochasticity played a dominant role from 150 to 900 km (separation between pairs of sites) and determinism dominated at more than 900 km (broad scale). On the Tibetan Plateau, determinism played a dominant role from 130 to 1200 km and stochasticity dominated at less than 130 km. Among the identifiable deterministic factors, soil pH showed the strongest influence on soil bacterial community structure and diversity across the North China Plain. Together, 23.9% of variation in soil microbial community composition could be explained, with environmental factors accounting for 19.7% and spatial parameters 4.1%.

CONCLUSIONS: Our findings revealed that (1) stochastic processes are relatively more important on the North China Plain, while deterministic processes are more important on the Tibetan Plateau; (2) soil pH was the major factor in shaping soil bacterial community structure of the North China Plain; and (3) most variation in soil microbial community composition could not be explained with existing environmental and spatial factors. Further studies are needed to dissect the influence of stochastic factors (e.g., mutations or extinctions) on soil microbial community distribution, which might make it easier to predictably manipulate the microbial community to produce better yield and soil sustainability outcomes.}, } @article {pmid29402317, year = {2018}, author = {Pizzol, D and Veronese, N and Marotta, C and Di Gennaro, F and Moiane, J and Chhaganlal, K and Monno, L and Putoto, G and Mazzucco, W and Saracino, A}, title = {Predictors of therapy failure in newly diagnosed pulmonary tuberculosis cases in Beira, Mozambique.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {99}, pmid = {29402317}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Antitubercular Agents/*therapeutic use ; Body Mass Index ; Coinfection ; Educational Status ; Employment/statistics & numerical data ; Female ; HIV Infections/diagnosis/virology ; Humans ; Male ; Malnutrition/microbiology/*physiopathology ; Mozambique ; Odds Ratio ; Outpatients ; Poverty/statistics & numerical data ; Prognosis ; Treatment Failure ; Tuberculosis, Pulmonary/*diagnosis/*drug therapy/microbiology ; }, abstract = {OBJECTIVE: Tuberculosis (TB) remains a major global health issue, ranking in the top ten causes of death worldwide. A deep understanding of factors influencing poor treatment outcomes may allow the development of additional treatment strategies, focused on the most vulnerable groups. Aims of the study were: (i) to evaluate the treatment outcome among TB subjects followed in an outpatient setting and (ii) to analyze factors associated with treatment failure in newly diagnosed patients with pulmonary TB in Beira, the second largest city of Mozambique.

RESULTS: A total of 301 TB adult patients (32.6% females) were enrolled. Among them, 62 (20.6%) experienced a treatment failure over a 6 months follow-up. On multivariate model, being males (O.R. = 1.73; 95% CI 1.28-2.15), absence of education (O.R. = 1.85; 95% CI 1.02-2.95), monthly income under 50 dollars (O.R. = 1.74; 95% CI 1.24-2.21) and being employed (O.R. = 1.57; 95% CI 1.21-1.70), low body mass index values (O.R. = 1.42; 95% CI 1.18-1.72) and HIV status (O.R. = 1.42; 95% CI 1.10-1.78) increased the likelihood of therapy failure over 6 months of follow-up. In this study, patients who need more medical attention were young males, malnourished, with low income and low educational degree and HIV positive. These subjects were more likely to fail therapy.}, } @article {pmid29402315, year = {2018}, author = {Daley, F and Bister, D and Markless, S and Set, P}, title = {Professionalism and non-technical skills in Radiology in the UK: a review of the national curriculum.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {96}, pmid = {29402315}, issn = {1756-0500}, mesh = {Clinical Competence/standards ; Curriculum/*standards ; Humans ; Internship and Residency ; Patient Safety ; Professionalism/ethics/*standards ; Radiology/*education ; United Kingdom ; Workforce ; }, abstract = {OBJECTIVE: To drive quality and safe clinical practice, professional values and non-technical skills need to be explicit in all postgraduate medical curricula and appropriate assessment tools should be available for teachers to apply. We interrogate a national Radiology curriculum for content on professionalism and assessment tools, comparing it with the Royal College of Physicians' 2005 document.

RESULTS: We found that whilst the knowledge for practising with professional values is embedded in the curriculum, the skills that have to be acquired have not been comprehensively developed. This is reflected in the restricted assessment tools that are mapped to each generic area. The terminology used in the Radiology curriculum was varied and the most frequently used descriptor for professionalism or behaviours pertaining to non-technical aspects was Good Medical Practice; a term used by our regulator, the General Medical Council, and to which our curriculum is mapped. If terminology is to be standardized in Britain collaboration with our regulator is key. We need standardized terminology to permit effective research and sharing of best practice. The Radiology curriculum encompasses all the values set out in the seminal document produced by the Royal College of Physicians in 2005, Doctors in society: medical professionalism in a changing world.}, } @article {pmid29402302, year = {2018}, author = {Shi, X and Yan, L and Yang, C and Yan, W and Moseley, DO and Wang, T and Liu, B and Di, R and Chen, P and Zhang, M}, title = {Identification of a major quantitative trait locus underlying salt tolerance in 'Jidou 12' soybean cultivar.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {95}, pmid = {29402302}, issn = {1756-0500}, support = {31000719//National Natural Science Foundation of China/ ; 31471522//National Natural Science Foundation of China/ ; 31201234//National Natural Science Foundation of China/ ; 31340043//National Natural Science Foundation of China (CN)/ ; CARS-004-PS06//China Agriculture Research System/ ; F13E006//Financial Foundation of Heibei Province/ ; B2012003//Postdoctoral Science Foundation of Heibei Province/ ; }, mesh = {Chlorophyll/biosynthesis/genetics ; Chromosome Mapping ; Chromosomes, Plant/*chemistry ; DNA, Plant/*genetics/metabolism ; Genetic Markers ; Plant Breeding ; Plant Leaves/genetics/metabolism ; *Quantitative Trait Loci ; Salinity ; Salt Tolerance/*genetics ; Soybeans/*genetics/metabolism ; }, abstract = {BACKGROUND: Identification of the quantitative trait locus (QTL) underlying salt tolerance is a prerequisite for marker-assisted selection in the salt-tolerant breeding process.

METHODS: In this study, the recombinant inbred lines derived from the salt-tolerant elite soybean cultivar 'Jidou 12' and the salt-sensitive elite cultivar 'Ji NF 58' were used to identify the QTL associated with salt tolerance, using both salt tolerance rating (STR) and leaf chlorophyll content (SPAD) as indicators.

RESULTS: A major salt-tolerant QTL, which was flanked by SSR markers GMABAB and Barcsoyssr_03_1421 on chromosome 3, was identified based on single-marker regression, single trait composite interval mapping, and multiple interval mapping analysis. For STR, the LOD ranged from 19.8 to 20.1; R2 ranged from 44.3 to 44.7%; and the additive effect ranged from 0.876 to 0.885 among the three mapping methods. For SPAD, the LOD ranged from 10.6 to 11.0; R2 ranged from 27.0 to 27.6%; and the additive effect ranged from 1.634 to 1.679 among the three mapping methods.

CONCLUSIONS: In this study, a major QTL conditioning salt tolerance on chromosome 3 was identified. The DNA markers closely associated with the QTLs might be useful in marker-assisted selection for soybean salt tolerance improvement in Huanghuaihai, China.}, } @article {pmid29402300, year = {2018}, author = {Burns, P and Oddi, S and Forzani, L and Tabacman, E and Reinheimer, J and Vinderola, G}, title = {Variability in gut mucosal secretory IgA in mice along a working day.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {98}, pmid = {29402300}, issn = {1756-0500}, mesh = {Analysis of Variance ; Animals ; Circadian Rhythm/*immunology ; Feces/chemistry ; Immunoglobulin A, Secretory/*biosynthesis ; Intestinal Mucosa/*immunology ; Intestine, Small/*immunology ; Male ; Mice ; Mice, Inbred BALB C ; Photoperiod ; }, abstract = {OBJECTIVE: To assess the variability of secretory immunoglobulin A (S-IgA) in the lumen and feces of mice along a working day.

RESULTS: Mice were maintained under a 12 h light-dark cycle, light period starting at 8 AM. S-IgA was determined in feces and intestinal content (after one or three washes) at three points along the day: at the beginning, in the middle and at the end of the light period (ELP). Significant reduction in the content of S-IgA in the small intestine fluid and in feces was observed at the end of the light cycle, which coincides with the end of a regular working day (8 PM) in any given animal facility. It was also observed that three washes of the small intestine were more effective than one flush to recover a significant higher amount of S-IgA, with the smallest coefficient of variation observed by the ELP. A smaller CV would imply a reduced number of animals needed to achieve the same meaningful results. The results may be useful when designing animal trials for the selection of probiotic candidates based on their capacity of activating S-IgA, since it would imply a more rational use of experimental animals.}, } @article {pmid29402230, year = {2018}, author = {Østbye, K and Taugbøl, A and Ravinet, M and Harrod, C and Pettersen, RA and Bernatchez, L and Vøllestad, LA}, title = {Ongoing niche differentiation under high gene flow in a polymorphic brackish water threespine stickleback (Gasterosteus aculeatus) population.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {14}, pmid = {29402230}, issn = {1471-2148}, support = {I will be funded by the institution through a special budget for publications in open access journals. My Deans name is Harry petter Andreassen (harry.andreassen@hihm.no; phone: +47-92831202). My current boss is Kristin Gangås as Harry is on sick leave, her e-mail is: kristin.gangas@hihm.no//Høgskolen i Hedmark/International ; }, mesh = {Animals ; Carbon Isotopes/metabolism ; *Ecosystem ; *Gene Flow ; Geography ; Lakes ; Linear Models ; Nitrogen Isotopes/metabolism ; Norway ; *Polymorphism, Genetic ; Predatory Behavior ; *Saline Waters ; Smegmamorpha/anatomy & histology/*genetics/parasitology ; }, abstract = {BACKGROUND: Marine threespine sticklebacks colonized and adapted to brackish and freshwater environments since the last Pleistocene glacial. Throughout the Holarctic, three lateral plate morphs are observed; the low, partial and completely plated morph. We test if the three plate morphs in the brackish water Lake Engervann, Norway, differ in body size, trophic morphology (gill raker number and length), niche (stable isotopes; δ15N, δ13C, and parasites (Theristina gasterostei, Trematoda spp.)), genetic structure (microsatellites) and the lateral-plate encoding Stn382 (Ectodysplasin) gene. We examine differences temporally (autumn 2006/spring 2007) and spatially (upper/lower sections of the lake - reflecting low versus high salinity).

RESULTS: All morphs belonged to one gene pool. The complete morph was larger than the low plated, with the partial morph intermediate. The number of lateral plates ranged 8-71, with means of 64.2 for complete, 40.3 for partial, and 14.9 for low plated morph. Stickleback δ15N was higher in the lower lake section, while δ13C was higher in the upper section. Stickleback isotopic values were greater in autumn. The low plated morph had larger variances in δ15N and δ13C than the other morphs. Sticklebacks in the upper section had more T. gasterostei than in the lower section which had more Trematoda spp. Sticklebacks had less T. gasterostei, but more Trematoda spp. in autumn than spring. Sticklebacks with few and short rakers had more T. gasterostei, while sticklebacks with longer rakers had more Trematoda. spp. Stickleback with higher δ15N values had more T. gasterostei, while sticklebacks with higher δ15N and δ13C values had more Trematoda spp. The low plated morph had fewer Trematoda spp. than other morphs.

CONCLUSIONS: Trait-ecology associations may imply that the three lateral plate morphs in the brackish water lagoon of Lake Engervann are experiencing ongoing divergent selection for niche and migratory life history strategies under high gene flow. As such, the brackish water zone may generally act as a generator of genomic diversity to be selected upon in the different environments where threespine sticklebacks can live.}, } @article {pmid29402227, year = {2018}, author = {Chiara, M and Gioiosa, S and Chillemi, G and D'Antonio, M and Flati, T and Picardi, E and Zambelli, F and Horner, DS and Pesole, G and Castrignanò, T}, title = {CoVaCS: a consensus variant calling system.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {120}, pmid = {29402227}, issn = {1471-2164}, support = {EPIGEN//Ministero dell'Istruzione, dell'Università e della Ricerca/International ; MTJU9H8: DICLIMAX: Strumentazione per diagnostica clinica basata su Next Generation sequencing di acidi nucleici,//Regione Puglia/International ; Bando di ricerca finalizzata e giovani ricercatori GR-2011-02347129//Ministero della Salute/International ; }, mesh = {Algorithms ; Computational Biology/*methods ; *Consensus Sequence ; Databases, Genetic ; INDEL Mutation ; Molecular Sequence Annotation ; Polymorphism, Single Nucleotide ; Sensitivity and Specificity ; Sequence Analysis, DNA/*methods ; *Software ; User-Computer Interface ; Web Browser ; Workflow ; }, abstract = {BACKGROUND: The advent and ongoing development of next generation sequencing technologies (NGS) has led to a rapid increase in the rate of human genome re-sequencing data, paving the way for personalized genomics and precision medicine. The body of genome resequencing data is progressively increasing underlining the need for accurate and time-effective bioinformatics systems for genotyping - a crucial prerequisite for identification of candidate causal mutations in diagnostic screens.

RESULTS: Here we present CoVaCS, a fully automated, highly accurate system with a web based graphical interface for genotyping and variant annotation. Extensive tests on a gold standard benchmark data-set -the NA12878 Illumina platinum genome- confirm that call-sets based on our consensus strategy are completely in line with those attained by similar command line based approaches, and far more accurate than call-sets from any individual tool. Importantly our system exhibits better sensitivity and higher specificity than equivalent commercial software.

CONCLUSIONS: CoVaCS offers optimized pipelines integrating state of the art tools for variant calling and annotation for whole genome sequencing (WGS), whole-exome sequencing (WES) and target-gene sequencing (TGS) data. The system is currently hosted at Cineca, and offers the speed of a HPC computing facility, a crucial consideration when large numbers of samples must be analysed. Importantly, all the analyses are performed automatically allowing high reproducibility of the results. As such, we believe that CoVaCS can be a valuable tool for the analysis of human genome resequencing studies. CoVaCS is available at: https://bioinformatics.cineca.it/covacs .}, } @article {pmid29402224, year = {2018}, author = {Zheng, Y and Li, F and Hao, L and Shedayi, AA and Guo, L and Ma, C and Huang, B and Xu, M}, title = {The optimal CO2 concentrations for the growth of three perennial grass species.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {27}, pmid = {29402224}, issn = {1471-2229}, support = {31400418//National Natural Science Foundation of China/International ; }, mesh = {Carbon Dioxide/*metabolism ; *Climate Change ; Festuca/*growth & development/metabolism ; Lolium/*growth & development/metabolism ; New Jersey ; Poa/*growth & development/metabolism ; Species Specificity ; }, abstract = {BACKGROUND: Grasslands are one of the most representative vegetation types accounting for about 20% of the global land area and thus the response of grasslands to climate change plays a pivotal role in terrestrial carbon balance. However, many current climate change models, based on earlier results of the doubling-CO2 experiments, may overestimate the CO2 fertilization effect, and as a result underestimate the potentially effects of future climate change on global grasslands when the atmospheric CO2 concentration goes beyond the optimal level. Here, we examined the optimal atmospheric CO2 concentration effect on CO2 fertilization and further on the growth of three perennial grasses in growth chambers with the CO2 concentration at 400, 600, 800, 1000, and 1200 ppm, respectively.

RESULTS: All three perennial grasses featured an apparent optimal CO2 concentration for growth. Initial increases in atmospheric CO2 concentration substantially enhanced the plant biomass of the three perennial grasses through the CO2 fertilization effect, but this CO2 fertilization effect was dramatically compromised with further rising atmospheric CO2 concentration beyond the optimum. The optimal CO2 concentration for the growth of tall fescue was lower than those of perennial ryegrass and Kentucky bluegrass, and thus the CO2 fertilization effect on tall fescue disappeared earlier than the other two species. By contrast, the weaker CO2 fertilization effect on the growth of perennial ryegrass and Kentucky bluegrass was sustained for a longer period due to their higher optimal CO2 concentrations than tall fescue. The limiting effects of excessively high CO2 concentrations may not only associate with changes in the biochemical and photochemical processes of photosynthesis, but also attribute to the declines in stomatal conductance and nitrogen availability.

CONCLUSIONS: In this study, we found apparent differences in the optimal CO2 concentrations for the growth of three grasses. These results suggest that the growth of different types of grasses may respond differently to future elevated CO2 concentrations through the CO2 fertilization effect, and thus potentially alter the community composition and structure of grasslands. Meanwhile, our results may also be helpful for improving current process-based ecological models to more accurately predict the structure and function of grassland ecosystems under future rising atmospheric CO2 concentration and climate change scenarios.}, } @article {pmid29402222, year = {2018}, author = {Ruesen, C and Chaidir, L and van Laarhoven, A and Dian, S and Ganiem, AR and Nebenzahl-Guimaraes, H and Huynen, MA and Alisjahbana, B and Dutilh, BE and van Crevel, R}, title = {Large-scale genomic analysis shows association between homoplastic genetic variation in Mycobacterium tuberculosis genes and meningeal or pulmonary tuberculosis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {122}, pmid = {29402222}, issn = {1471-2164}, support = {09-PD-14//Koninklijke Nederlandse Akademie van Wetenschappen/International ; 017.106.310//ZonMw/International ; 864.14.004//ZonMw/International ; }, mesh = {Computational Biology/methods ; *Genes, Bacterial ; *Genetic Variation ; *Genome, Bacterial ; Genomics/methods ; Humans ; Indonesia ; Mycobacterium tuberculosis/classification/*genetics ; Phenotype ; Phylogeny ; Polymorphism, Single Nucleotide ; Tuberculosis, Meningeal/*microbiology ; Tuberculosis, Pulmonary/*microbiology ; }, abstract = {BACKGROUND: Meningitis is the most severe manifestation of tuberculosis. It is largely unknown why some people develop pulmonary TB (PTB) and others TB meningitis (TBM); we examined if the genetic background of infecting M. tuberculosis strains may be relevant.

METHODS: We whole-genome sequenced M. tuberculosis strains isolated from 322 HIV-negative tuberculosis patients from Indonesia and compared isolates from patients with TBM (n = 106) and PTB (n = 216). Using a phylogeny-adjusted genome-wide association method to count homoplasy events we examined phenotype-related changes at specific loci or genes in parallel branches of the phylogenetic tree. Enrichment scores for the TB phenotype were calculated on single nucleotide polymorphism (SNP), gene, and pathway level. Genetic associations were validated in an independent set of isolates.

RESULTS: Strains belonged to the East-Asian lineage (36.0%), Euro-American lineage (61.5%), and Indo-Oceanic lineage (2.5%). We found no association between lineage and phenotype (Chi-square = 4.556; p = 0.207). Large genomic differences were observed between isolates; the minimum pairwise genetic distance varied from 17 to 689 SNPs. Using the phylogenetic tree, based on 28,544 common variable positions, we selected 54 TBM and 54 PTB isolates in terminal branch sets with distinct phenotypes. Genetic variation in Rv0218, and absence of Rv3343c, and nanK were significantly associated with disease phenotype in these terminal branch sets, and confirmed in the validation set of 214 unpaired isolates.

CONCLUSIONS: Using homoplasy counting we identified genetic variation in three separate genes to be associated with the TB phenotype, including one (Rv0218) which encodes a secreted protein that could play a role in host-pathogen interaction by altering pathogen recognition or acting as virulence effector.}, } @article {pmid29402221, year = {2018}, author = {Yan, L and Liu, Z and Xu, H and Zhang, X and Zhao, A and Liang, F and Xin, M and Peng, H and Yao, Y and Sun, Q and Ni, Z}, title = {Transcriptome analysis reveals potential mechanisms for different grain size between natural and resynthesized allohexaploid wheats with near-identical AABB genomes.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {28}, pmid = {29402221}, issn = {1471-2229}, support = {31290212//National Natural Science Foundation of China (CN)/International ; 91435204//National Natural Science Foundation of China/International ; 31601305//National Natural Science Foundation of China/International ; 2016YFD0100801//National Key Research and Development Program of China/International ; }, mesh = {Edible Grain/genetics/growth & development ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Genetic Variation ; *Genome, Plant ; Plant Breeding ; Polyploidy ; *Transcriptome ; Triticum/*genetics/growth & development ; }, abstract = {BACKGROUND: Common wheat is a typical allohexaploid species (AABBDD) derived from the interspecific crossing between allotetraploid wheat (AABB) and Aegilops tauschii (DD). Wide variation in grain size and shape observed among Aegilops tauschii can be retained in synthetic allohexaploid wheats, but the underlying mechanism remains enigmatic. Here, the natural and resynthesized allohexaploid wheats with near-identical AB genomes and different D genomes (TAA10 and XX329) were employed for analysis.

RESULTS: Significant differences in grain size and weight between TAA10 and XX329 were observed at the early stages of development, which could be mainly attributed to the higher growth rates of the pericarp and endosperm cells in XX329 compared to TAA10. Furthermore, comparative transcriptome analysis identified that 8891 of 69,711 unigenes (12.75%) were differentially expressed between grains at 6 days after pollination (DAP) of TAA10 and XX329, including 5314 up-regulated and 3577 down-regulated genes in XX329 compared to TAA10. The MapMan functional annotation and enrichment analysis revealed that the differentially expressed genes were significantly enriched in categories of cell wall, carbohydrate and hormone metabolism. Notably, consistent with the up-regulation of sucrose synthase genes in resynthesized relative to natural allohexaploid wheat, the resynthesized allohexaploid wheat accumulated much higher contents of glucose and fructose in 6-DAP grains than those of the natural allohexaploid wheat.

CONCLUSIONS: These data indicated that the genetic variation of the D genome induced drastic alterations of gene expression in grains of the natural and resynthesized allohexaploid wheats, which may contribute to the observed differences in grain size and weight.}, } @article {pmid29402217, year = {2018}, author = {Dard-Dascot, C and Naquin, D and d'Aubenton-Carafa, Y and Alix, K and Thermes, C and van Dijk, E}, title = {Systematic comparison of small RNA library preparation protocols for next-generation sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {118}, pmid = {29402217}, issn = {1471-2164}, mesh = {Animals ; Bias ; *Computational Biology/methods ; *Gene Library ; *High-Throughput Nucleotide Sequencing/methods/standards ; Humans ; MicroRNAs/chemistry/*genetics ; Nucleic Acid Conformation ; Plants/genetics ; Reproducibility of Results ; *Sequence Analysis, RNA/methods/standards ; }, abstract = {BACKGROUND: Next-generation sequencing technologies have revolutionized the study of small RNAs (sRNAs) on a genome-wide scale. However, classical sRNA library preparation methods introduce serious bias, mainly during adapter ligation steps. Several types of sRNA including plant microRNAs (miRNA), piwi-interacting RNAs (piRNA) in insects, nematodes and mammals, and small interfering RNAs (siRNA) in insects and plants contain a 2'-O-methyl (2'-OMe) modification at their 3' terminal nucleotide. This inhibits 3' adapter ligation and makes library preparation particularly challenging. To reduce bias, the NEBNext kit (New England Biolabs) uses polyethylene glycol (PEG), the NEXTflex V2 kit (BIOO Scientific) uses both randomised adapters and PEG, and the novel SMARTer (Clontech) and CATS (Diagenode) kits avoid ligation altogether. Here we compared these methods with Illumina's classical TruSeq protocol regarding the detection of normal and 2' OMe RNAs. In addition, we modified the TruSeq and NEXTflex protocols to identify conditions that improve performance.

RESULTS: Among the five kits tested with their respective standard protocols, the SMARTer and CATS kits had the lowest levels of bias but also had a strong formation of side products, and as a result performed relatively poorly with biological samples; NEXTflex detected the largest numbers of different miRNAs. The use of a novel type of randomised adapters called MidRand-Like (MRL) adapters and PEG improved the detection of 2' OMe RNAs both in the TruSeq as well as in the NEXTflex protocol.

CONCLUSIONS: While it is commonly accepted that biases in sRNA library preparation protocols are mainly due to adapter ligation steps, the ligation-free protocols were not the best performing methods. Our modified versions of the TruSeq and NEXTflex protocols provide an improved tool for the study of 2' OMe RNAs.}, } @article {pmid29402215, year = {2018}, author = {Borges, R and Johnson, WE and O'Brien, SJ and Gomes, C and Heesy, CP and Antunes, A}, title = {Adaptive genomic evolution of opsins reveals that early mammals flourished in nocturnal environments.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {121}, pmid = {29402215}, issn = {1471-2164}, mesh = {*Adaptation, Biological ; Animals ; Biological Evolution ; *Environment ; *Evolution, Molecular ; *Genome ; Mammals/*genetics ; Opsins/chemistry/*genetics ; Selection, Genetic ; Synteny ; }, abstract = {BACKGROUND: Based on evolutionary patterns of the vertebrate eye, Walls (1942) hypothesized that early placental mammals evolved primarily in nocturnal habitats. However, not only Eutheria, but all mammals show photic characteristics (i.e. dichromatic vision, rod-dominated retina) suggestive of a scotopic eye design.

RESULTS: Here, we used integrative comparative genomic and phylogenetic methodologies employing the photoreceptive opsin gene family in 154 mammals to test the likelihood of a nocturnal period in the emergence of all mammals. We showed that mammals possess genomic patterns concordant with a nocturnal ancestry. The loss of the RH2, VA, PARA, PARIE and OPN4x opsins in all mammals led us to advance a probable and most-parsimonious hypothesis of a global nocturnal bottleneck that explains the loss of these genes in the emerging lineage (> > 215.5 million years ago). In addition, ancestral character reconstruction analyses provided strong evidence that ancestral mammals possessed a nocturnal lifestyle, ultra-violet-sensitive vision, low visual acuity and low orbit convergence (i.e. panoramic vision).

CONCLUSIONS: Overall, this study provides insight into the evolutionary history of the mammalian eye while discussing important ecological aspects of the photic paleo-environments ancestral mammals have occupied.}, } @article {pmid29402214, year = {2018}, author = {Darracq, A and Vitte, C and Nicolas, S and Duarte, J and Pichon, JP and Mary-Huard, T and Chevalier, C and Bérard, A and Le Paslier, MC and Rogowsky, P and Charcosset, A and Joets, J}, title = {Sequence analysis of European maize inbred line F2 provides new insights into molecular and chromosomal characteristics of presence/absence variants.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {119}, pmid = {29402214}, issn = {1471-2164}, support = {ANR-10-GENM-0003//Agence Nationale de la Recherche/International ; ANR-10-BTBR-01-01//Agence Nationale de la Recherche/International ; }, mesh = {*Chromosomes, Plant ; Computational Biology/methods ; DNA Copy Number Variations ; DNA Transposable Elements ; Evolution, Molecular ; *Genetic Variation ; *Genome, Plant ; Genomics/methods ; *Inbreeding ; Linkage Disequilibrium ; Poaceae/genetics ; Sequence Analysis, DNA ; Zea mays/*genetics ; }, abstract = {BACKGROUND: Maize is well known for its exceptional structural diversity, including copy number variants (CNVs) and presence/absence variants (PAVs), and there is growing evidence for the role of structural variation in maize adaptation. While PAVs have been described in this important crop species, they have been only scarcely characterized at the sequence level and the extent of presence/absence variation and relative chromosomal landscape of inbred-specific regions remain to be elucidated.

RESULTS: De novo genome sequencing of the French F2 maize inbred line revealed 10,044 novel genomic regions larger than 1 kb, making up 88 Mb of DNA, that are present in F2 but not in B73 (PAV). This set of maize PAV sequences allowed us to annotate PAV content and to analyze sequence breakpoints. Using PAV genotyping on a collection of 25 temperate lines, we also analyzed Linkage Disequilibrium in PAVs and flanking regions, and PAV frequencies within maize genetic groups.

CONCLUSIONS: We highlight the possible role of MMEJ-type double strand break repair in maize PAV formation and discover 395 new genes with transcriptional support. Pattern of linkage disequilibrium within PAVs strikingly differs from this of flanking regions and is in accordance with the intuition that PAVs may recombine less than other genomic regions. We show that most PAVs are ancient, while some are found only in European Flint material, thus pinpointing structural features that may be at the origin of adaptive traits involved in the success of this material. Characterization of such PAVs will provide useful material for further association genetic studies in European and temperate maize.}, } @article {pmid29402213, year = {2018}, author = {Bush, EC and Clark, AE and DeRanek, CA and Eng, A and Forman, J and Heath, K and Lee, AB and Stoebel, DM and Wang, Z and Wilber, M and Wu, H}, title = {xenoGI: reconstructing the history of genomic island insertions in clades of closely related bacteria.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {32}, pmid = {29402213}, issn = {1471-2105}, support = {52007544/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Bacteria/*genetics ; Computer Simulation ; Evolution, Molecular ; Genome, Bacterial ; Genomic Islands/*genetics ; *Phylogeny ; Reproducibility of Results ; *Software ; Time Factors ; }, abstract = {BACKGROUND: Genomic islands play an important role in microbial genome evolution, providing a mechanism for strains to adapt to new ecological conditions. A variety of computational methods, both genome-composition based and comparative, have been developed to identify them. Some of these methods are explicitly designed to work in single strains, while others make use of multiple strains. In general, existing methods do not identify islands in the context of the phylogeny in which they evolved. Even multiple strain approaches are best suited to identifying genomic islands that are present in one strain but absent in others. They do not automatically recognize islands which are shared between some strains in the clade or determine the branch on which these islands inserted within the phylogenetic tree.

RESULTS: We have developed a software package, xenoGI, that identifies genomic islands and maps their origin within a clade of closely related bacteria, determining which branch they inserted on. It takes as input a set of sequenced genomes and a tree specifying their phylogenetic relationships. Making heavy use of synteny information, the package builds gene families in a species-tree-aware way, and then attempts to combine into islands those families whose members are adjacent and whose most recent common ancestor is shared. The package provides a variety of text-based analysis functions, as well as the ability to export genomic islands into formats suitable for viewing in a genome browser. We demonstrate the capabilities of the package with several examples from enteric bacteria, including an examination of the evolution of the acid fitness island in the genus Escherichia. In addition we use output from simulations and a set of known genomic islands from the literature to show that xenoGI can accurately identify genomic islands and place them on a phylogenetic tree.

CONCLUSIONS: xenoGI is an effective tool for studying the history of genomic island insertions in a clade of microbes. It identifies genomic islands, and determines which branch they inserted on within the phylogenetic tree for the clade. Such information is valuable because it helps us understand the adaptive path that has produced living species.}, } @article {pmid29402212, year = {2018}, author = {Chiu, B and Pyysalo, S and Vulić, I and Korhonen, A}, title = {Bio-SimVerb and Bio-SimLex: wide-coverage evaluation sets of word similarity in biomedicine.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {33}, pmid = {29402212}, issn = {1471-2105}, support = {MR/M013049/1//Medical Research Council/United Kingdom ; 648909//H2020 European Research Council/International ; }, mesh = {*Biomedical Technology ; Databases as Topic ; Humans ; Language ; Natural Language Processing ; *Semantics ; *Software ; }, abstract = {BACKGROUND: Word representations support a variety of Natural Language Processing (NLP) tasks. The quality of these representations is typically assessed by comparing the distances in the induced vector spaces against human similarity judgements. Whereas comprehensive evaluation resources have recently been developed for the general domain, similar resources for biomedicine currently suffer from the lack of coverage, both in terms of word types included and with respect to the semantic distinctions. Notably, verbs have been excluded, although they are essential for the interpretation of biomedical language. Further, current resources do not discern between semantic similarity and semantic relatedness, although this has been proven as an important predictor of the usefulness of word representations and their performance in downstream applications.

RESULTS: We present two novel comprehensive resources targeting the evaluation of word representations in biomedicine. These resources, Bio-SimVerb and Bio-SimLex, address the previously mentioned problems, and can be used for evaluations of verb and noun representations respectively. In our experiments, we have computed the Pearson's correlation between performances on intrinsic and extrinsic tasks using twelve popular state-of-the-art representation models (e.g. word2vec models). The intrinsic-extrinsic correlations using our datasets are notably higher than with previous intrinsic evaluation benchmarks such as UMNSRS and MayoSRS. In addition, when evaluating representation models for their abilities to capture verb and noun semantics individually, we show a considerable variation between performances across all models.

CONCLUSION: Bio-SimVerb and Bio-SimLex enable intrinsic evaluation of word representations. This evaluation can serve as a predictor of performance on various downstream tasks in the biomedical domain. The results on Bio-SimVerb and Bio-SimLex using standard word representation models highlight the importance of developing dedicated evaluation resources for NLP in biomedicine for particular word classes (e.g. verbs). These are needed to identify the most accurate methods for learning class-specific representations. Bio-SimVerb and Bio-SimLex are publicly available.}, } @article {pmid29402211, year = {2018}, author = {Bragg, JG and Potter, S and Afonso Silva, AC and Hoskin, CJ and Bai, BYH and Moritz, C}, title = {Phylogenomics of a rapid radiation: the Australian rainbow skinks.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {15}, pmid = {29402211}, issn = {1471-2148}, mesh = {Alleles ; Animals ; Australia ; Bayes Theorem ; Exons/genetics ; *Genomics ; Lizards/*classification/*genetics ; *Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {BACKGROUND: The application of target capture with next-generation sequencing now enables phylogenomic analyses of rapidly radiating clades of species. But such analyses are complicated by extensive incomplete lineage sorting, demanding the use of methods that consider this process explicitly, such as the multispecies coalescent (MSC) model. However, the MSC makes strong assumptions about divergence history and population structure, and when using the full Bayesian implementation, current computational limits mean that relatively few loci and samples can be analysed for even modest sized radiations. We explore these issues through analyses of an extensive (> 1000 loci) dataset for the Australian rainbow skinks. This group consists of 3 genera and 41 described species, which likely diversified rapidly in Australia during the mid-late Miocene to occupy rainforest, woodland, and rocky habitats with corresponding diversity of morphology and breeding colouration. Previous phylogenetic analyses of this group have revealed short inter-nodes and high discordance among loci, limiting the resolution of inferred trees. A further complication is that many species have deep phylogeographic structure - this poses the question of how to sample individuals within species for analyses using the MSC.

RESULTS: Phylogenies obtained using concatenation and summary coalescent species tree approaches to the full dataset are well resolved with generally consistent topology, including for previously intractable relationships near the base of the clade. As expected, branch lengths at the tips are substantially overestimated using concatenation. Comparisons of different strategies for sampling haplotypes for full Bayesian MSC analyses (for one clade and using smaller sets of loci) revealed, unexpectedly, that combining haplotypes across divergent phylogeographic lineages yielded consistent species trees.

CONCLUSIONS: This study of more than 1000 loci provides a strongly-supported estimate of the phylogeny of the Australian rainbow skinks, which will inform future research on the evolution and taxonomy of this group. Our analyses suggest that species tree estimation with the MSC can be quite robust to violation of the assumption that the individuals representing a taxon are sampled from a panmictic population.}, } @article {pmid29402210, year = {2018}, author = {Condon, DE and Tran, PV and Lien, YC and Schug, J and Georgieff, MK and Simmons, RA and Won, KJ}, title = {Defiant: (DMRs: easy, fast, identification and ANnoTation) identifies differentially Methylated regions from iron-deficient rat hippocampus.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {31}, pmid = {29402210}, issn = {1471-2105}, support = {R01 HD029421/NH/NIH HHS/United States ; R01 DK106027/DK/NIDDK NIH HHS/United States ; R01 DK106027/NH/NIH HHS/United States ; R01 NS099178/NS/NINDS NIH HHS/United States ; P30 DK019525/DK/NIDDK NIH HHS/United States ; R01 HD029421/HD/NICHD NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Animals, Newborn ; CpG Islands/genetics ; DNA Methylation/*genetics ; Databases, Genetic ; Female ; Fetus/metabolism ; Hippocampus/*metabolism ; Iron/*deficiency ; *Molecular Sequence Annotation ; Rats, Sprague-Dawley ; *Software ; Time Factors ; }, abstract = {BACKGROUND: Identification of differentially methylated regions (DMRs) is the initial step towards the study of DNA methylation-mediated gene regulation. Previous approaches to call DMRs suffer from false prediction, use extreme resources, and/or require library installation and input conversion.

RESULTS: We developed a new approach called Defiant to identify DMRs. Employing Weighted Welch Expansion (WWE), Defiant showed superior performance to other predictors in the series of benchmarking tests on artificial and real data. Defiant was subsequently used to investigate DNA methylation changes in iron-deficient rat hippocampus. Defiant identified DMRs close to genes associated with neuronal development and plasticity, which were not identified by its competitor. Importantly, Defiant runs between 5 to 479 times faster than currently available software packages. Also, Defiant accepts 10 different input formats widely used for DNA methylation data.

CONCLUSIONS: Defiant effectively identifies DMRs for whole-genome bisulfite sequencing (WGBS), reduced-representation bisulfite sequencing (RRBS), Tet-assisted bisulfite sequencing (TAB-seq), and HpaII tiny fragment enrichment by ligation-mediated PCR-tag (HELP) assays.}, } @article {pmid29402209, year = {2018}, author = {Strand, TM and Lundkvist, Å and Olsen, B and Gustafsson, L}, title = {Breeding consequences of flavivirus infection in the collared flycatcher.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {13}, pmid = {29402209}, issn = {1471-2148}, mesh = {Animals ; Antibodies, Viral/blood ; Antibody Specificity/immunology ; Female ; Flaviviridae/*physiology ; Flavivirus Infections/blood/immunology/*pathology ; Genome, Viral ; Linear Models ; Male ; Reproduction/*physiology ; Songbirds/blood/immunology/*virology ; }, abstract = {BACKGROUND: The breeding consequences of virus infections have rarely been studied in avian natural breeding populations. In this paper we investigated the links between humoral immunity following a natural flavivirus infection and reproduction in a wild bird population of collared flycatcher (Ficedula albicollis). We analyzed plasma from 744 birds for antibodies and correlated these results to a number of reproductive components.

RESULTS: Nearly one third (27.8%) of the sampled collared flycatchers were found seropositive for flavivirus. Males had significantly more frequently flavivirus antibodies (32.3%) than females (25.1%). Seropositive females differed significantly from seronegative females in four traits: they had earlier lay date, higher body weight, higher survival rate and were older than seronegative females. The females did not differ in clutch size, number of fledged young or number of recruited young. Seropositive males had female partners with earlier lay date, i.e. the males bred earlier and they also produced more fledged young than seronegative males. In contrast, the males did not differ in clutch size, number of recruited young, male weight, age or survival. Interestingly, seropositive males had larger ornament, forehead badge size, than seronegative males.

CONCLUSIONS: Collared flycatchers with an antibody response against flavivirus were more successful than birds with no antibody response, for any of the measured life history traits. The positive link between flavivirus antibody presence and life-history trait levels suggest that it is condition dependent in the collared flycatcher.}, } @article {pmid29401317, year = {2018}, author = {Kosakovsky Pond, SL and Weaver, S and Leigh Brown, AJ and Wertheim, JO}, title = {HIV-TRACE (TRAnsmission Cluster Engine): a Tool for Large Scale Molecular Epidemiology of HIV-1 and Other Rapidly Evolving Pathogens.}, journal = {Molecular biology and evolution}, volume = {35}, number = {7}, pages = {1812-1819}, pmid = {29401317}, issn = {1537-1719}, support = {K01 AI110181/AI/NIAID NIH HHS/United States ; R01 AI134384/AI/NIAID NIH HHS/United States ; R01 GM093939/GM/NIGMS NIH HHS/United States ; U01 GM110749/GM/NIGMS NIH HHS/United States ; }, abstract = {In modern applications of molecular epidemiology, genetic sequence data are routinely used to identify clusters of transmission in rapidly evolving pathogens, most notably HIV-1. Traditional 'shoe-leather' epidemiology infers transmission clusters by tracing chains of partners sharing epidemiological connections (e.g., sexual contact). Here, we present a computational tool for identifying a molecular transmission analog of such clusters: HIV-TRACE (TRAnsmission Cluster Engine). HIV-TRACE implements an approach inspired by traditional epidemiology, by identifying chains of partners whose viral genetic relatedness imply direct or indirect epidemiological connections. Molecular transmission clusters are constructed using codon-aware pairwise alignment to a reference sequence followed by pairwise genetic distance estimation among all sequences. This approach is computationally tractable and is capable of identifying HIV-1 transmission clusters in large surveillance databases comprising tens or hundreds of thousands of sequences in near real time, that is, on the order of minutes to hours. HIV-TRACE is available at www.hivtrace.org and from www.github.com/veg/hivtrace, along with the accompanying result visualization module from www.github.com/veg/hivtrace-viz. Importantly, the approach underlying HIV-TRACE is not limited to the study of HIV-1 and can be applied to study outbreaks and epidemics of other rapidly evolving pathogens.}, } @article {pmid29401285, year = {2018}, author = {Dunivin, TK and Shade, A}, title = {Community structure explains antibiotic resistance gene dynamics over a temperature gradient in soil.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, pmid = {29401285}, issn = {1574-6941}, abstract = {Soils are reservoirs of antibiotic resistance genes (ARGs), but environmental dynamics of ARGs are largely unknown. Long-term disturbances offer opportunities to examine microbiome responses at scales relevant for both ecological and evolutionary processes and can be insightful for studying ARGs. We examined ARGs in soils overlying the underground coal seam fire in Centralia, PA, which has been burning since 1962. As the fire progresses, previously hot soils can recover to ambient temperatures, which creates a gradient of fire impact. We examined metagenomes from surface soils along this gradient to examine ARGs using a gene-targeted assembler. We targeted 35 clinically relevant ARGs and two horizontal gene transfer-related genes (intI and repA). We detected 17 ARGs in Centralia: AAC6-Ia, adeB, bla_A, bla_B, bla_C, cmlA, dfra12, intI, sul2, tetA, tetW, tetX, tolC, vanA, vanH, vanX and vanZ. The diversity and abundance of bla_A, bla_B, dfra12 and tolC decreased with soil temperature, and changes in ARGs were largely explained by changes in community structure. We observed sequence-specific biogeography along the temperature gradient and observed compositional shifts in bla_A, dfra12 and intI. These results suggest that increased temperatures can reduce soil ARGs but that this is largely due to a concomitant reduction in community-level diversity.}, } @article {pmid29401267, year = {2018}, author = {Liu, S and Chen, Q and Ma, T and Wang, M and Ni, J}, title = {Genomic insights into metabolic potentials of two simultaneous aerobic denitrification and phosphorus removal bacteria, Achromobacter sp. GAD3 and Agrobacterium sp. LAD9.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy020}, pmid = {29401267}, issn = {1574-6941}, abstract = {Bacteria capable of simultaneous aerobic denitrification and phosphorus removal (SADPR) are promising for the establishment of novel one-stage wastewater treatment systems. Nevertheless, insights into the metabolic potential of SADPR-related bacteria are limited. Here, comprehensive metabolic models of two efficient SADPR bacteria, Achromobacter sp. GAD3 and Agrobacterium sp. LAD9, were obtained for the first time by high-throughput genome sequencing. With succinate as the preferred carbon source, both strains employed a complete TCA cycle as the major carbon metabolism for potentials of various organic acids and complex carbon oxidation. Complete and truncated aerobic denitrification routes were confirmed in GAD3 and LAD9, respectively, facilitated by all the major components of the electron transfer chain via oxidative phosphorylation. Comparative genome analysis revealed distinctive ecological niches involved in denitrification among different phylogenetic clades within Achromobacter and Agrobacterium. Excellent phosphorus removal capacities were contributed by inorganic phosphate uptake, polyphosphate synthesis and phosphonate metabolism. Additionally, the physiology of GAD3/LAD9 is different from that displayed by most available polyphosphate accumulating organisms, and reveals both strains to be more versatile, carrying out potentials for diverse organics degradation and outstanding SADPR capacity within a single organism. The functional exploration of SADPR bacteria broadens their significant prospects for application in concurrent aerobic carbon and nutrient removal.}, } @article {pmid29401000, year = {2018}, author = {Goldenzweig, A and Fleishman, SJ}, title = {Principles of Protein Stability and Their Application in Computational Design.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {105-129}, doi = {10.1146/annurev-biochem-062917-012102}, pmid = {29401000}, issn = {1545-4509}, abstract = {Proteins are increasingly used in basic and applied biomedical research. Many proteins, however, are only marginally stable and can be expressed in limited amounts, thus hampering research and applications. Research has revealed the thermodynamic, cellular, and evolutionary principles and mechanisms that underlie marginal stability. With this growing understanding, computational stability design methods have advanced over the past two decades starting from methods that selectively addressed only some aspects of marginal stability. Current methods are more general and, by combining phylogenetic analysis with atomistic design, have shown drastic improvements in solubility, thermal stability, and aggregation resistance while maintaining the protein's primary molecular activity. Stability design is opening the way to rational engineering of improved enzymes, therapeutics, and vaccines and to the application of protein design methodology to large proteins and molecular activities that have proven challenging in the past.}, } @article {pmid29400986, year = {2018}, author = {Contreras, JL and Knoppers, BM}, title = {The Genomic Commons.}, journal = {Annual review of genomics and human genetics}, volume = {19}, number = {}, pages = {429-453}, doi = {10.1146/annurev-genom-083117-021552}, pmid = {29400986}, issn = {1545-293X}, abstract = {Over its 30 or so years of existence, the genomic commons-the worldwide collection of publicly accessible repositories of human and nonhuman genomic data-has enjoyed remarkable, perhaps unprecedented, success. Thanks to the rapid public data release policies initiated by the Human Genome Project, free access to a vast array of scientific data is now the norm, not only in genomics, but in scientific disciplines of all descriptions. And far from being a monolithic creation of bureaucratic fiat, the genomic commons is an exemplar of polycentric, multistakeholder governance. But like all dynamic and rapidly evolving systems, the genomic commons is not without its challenges. Issues involving scientific priority, intellectual property, individual privacy, and informed consent, in an environment of data sets of exponentially expanding size and complexity, must be addressed in the near term. In this review, we describe the characteristics and unique history of the genomic commons, then address some of the trends, challenges, and opportunities that we envision for this valuable public resource in the years to come.}, } @article {pmid29400701, year = {2018}, author = {Rehfeld, K and Münch, T and Ho, SL and Laepple, T}, title = {Global patterns of declining temperature variability from the Last Glacial Maximum to the Holocene.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {356-359}, pmid = {29400701}, issn = {1476-4687}, abstract = {Changes in climate variability are as important for society to address as are changes in mean climate. Contrasting temperature variability during the Last Glacial Maximum and the Holocene can provide insights into the relationship between the mean state of the climate and its variability. However, although glacial-interglacial changes in variability have been quantified for Greenland, a global view remains elusive. Here we use a network of marine and terrestrial temperature proxies to show that temperature variability decreased globally by a factor of four as the climate warmed by 3-8 degrees Celsius from the Last Glacial Maximum (around 21,000 years ago) to the Holocene epoch (the past 11,500 years). This decrease had a clear zonal pattern, with little change in the tropics (by a factor of only 1.6-2.8) and greater change in the mid-latitudes of both hemispheres (by a factor of 3.3-14). By contrast, Greenland ice-core records show a reduction in temperature variability by a factor of 73, suggesting influences beyond local temperature or a decoupling of atmospheric and global surface temperature variability for Greenland. The overall pattern of reduced variability can be explained by changes in the meridional temperature gradient, a mechanism that points to further decreases in temperature variability in a warmer future.}, } @article {pmid29400700, year = {2018}, author = {Jones, TR and Roberts, WHG and Steig, EJ and Cuffey, KM and Markle, BR and White, JWC}, title = {Southern Hemisphere climate variability forced by Northern Hemisphere ice-sheet topography.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {351-355}, pmid = {29400700}, issn = {1476-4687}, abstract = {The presence of large Northern Hemisphere ice sheets and reduced greenhouse gas concentrations during the Last Glacial Maximum fundamentally altered global ocean-atmosphere climate dynamics. Model simulations and palaeoclimate records suggest that glacial boundary conditions affected the El Niño-Southern Oscillation, a dominant source of short-term global climate variability. Yet little is known about changes in short-term climate variability at mid- to high latitudes. Here we use a high-resolution water isotope record from West Antarctica to demonstrate that interannual to decadal climate variability at high southern latitudes was almost twice as large at the Last Glacial Maximum as during the ensuing Holocene epoch (the past 11,700 years). Climate model simulations indicate that this increased variability reflects an increase in the teleconnection strength between the tropical Pacific and West Antarctica, owing to a shift in the mean location of tropical convection. This shift, in turn, can be attributed to the influence of topography and albedo of the North American ice sheets on atmospheric circulation. As the planet deglaciated, the largest and most abrupt decline in teleconnection strength occurred between approximately 16,000 years and 15,000 years ago, followed by a slower decline into the early Holocene.}, } @article {pmid29399790, year = {2018}, author = {Wang, XY and Quan, QM and Wang, B and Li, YX and Huang, SQ}, title = {Pollen competition between morphs in a pollen-color dimorphic herb and the loss of phenotypic polymorphism within populations.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {785-797}, doi = {10.1111/evo.13445}, pmid = {29399790}, issn = {1558-5646}, abstract = {Flower color polymorphism is relatively uncommon in natural flowering plants, suggesting that maintenance of different color morphs within populations is difficult. To address the selective mechanisms shaping pollen-color dimorphism, pollinator preferences and reproductive performance were studied over three years in Epimedium pubescens in which some populations had plants with either green or yellow pollen (and anthers). Visitation rate and pollen removal and receipt by the bee pollinator (Andrena emeishanica) did not differ between the two color morphs. Compared to the green morph, siring success of the yellow morph's pollen was lower, but that of mixtures of pollen from green and yellow morphs was lowest. This difference, corresponding to in vivo and ex vivo experiments on pollen performance, indicated that pollen germination, rather than tube growth, of the green morph was higher than that of the yellow morph and was seriously constrained in both morphs if a pollen competitor was present. A rare green morph may invade a yellow-morph population, but the coexistence of pollen color variants is complicated by the reduced siring success of mixed pollinations. Potential pollen competition between morphs may have discouraged the maintenance of multiple phenotypes within populations, a cryptic mechanism of competitive exclusion.}, } @article {pmid29398705, year = {2018}, author = {Riglar, DT and Silver, PA}, title = {Engineering bacteria for diagnostic and therapeutic applications.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {214-225}, pmid = {29398705}, issn = {1740-1534}, abstract = {Our ability to generate bacterial strains with unique and increasingly complex functions has rapidly expanded in recent times. The capacity for DNA synthesis is increasing and costing less; new tools are being developed for fast, large-scale genetic manipulation; and more tested genetic parts are available for use, as is the knowledge of how to use them effectively. These advances promise to unlock an exciting array of 'smart' bacteria for clinical use but will also challenge scientists to better optimize preclinical testing regimes for early identification and validation of promising strains and strategies. Here, we review recent advances in the development and testing of engineered bacterial diagnostics and therapeutics. We highlight new technologies that will assist the development of more complex, robust and reliable engineered bacteria for future clinical applications, and we discuss approaches to more efficiently evaluate engineered strains throughout their preclinical development.}, } @article {pmid29398704, year = {2018}, author = {Kuypers, MMM and Marchant, HK and Kartal, B}, title = {The microbial nitrogen-cycling network.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {263-276}, pmid = {29398704}, issn = {1740-1534}, abstract = {Nitrogen is an essential component of all living organisms and the main nutrient limiting life on our planet. By far, the largest inventory of freely accessible nitrogen is atmospheric dinitrogen, but most organisms rely on more bioavailable forms of nitrogen, such as ammonium and nitrate, for growth. The availability of these substrates depends on diverse nitrogen-transforming reactions that are carried out by complex networks of metabolically versatile microorganisms. In this Review, we summarize our current understanding of the microbial nitrogen-cycling network, including novel processes, their underlying biochemical pathways, the involved microorganisms, their environmental importance and industrial applications.}, } @article {pmid29398703, year = {2018}, author = {Hannan, AJ}, title = {Tandem repeats mediating genetic plasticity in health and disease.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {286-298}, pmid = {29398703}, issn = {1471-0064}, abstract = {Accumulating evidence suggests that many classes of DNA repeats exhibit attributes that distinguish them from other genetic variants, including the fact that they are more liable to mutation; this enables them to mediate genetic plasticity. The expansion of tandem repeats, particularly of short tandem repeats, can cause a range of disorders (including Huntington disease, various ataxias, motor neuron disease, frontotemporal dementia, fragile X syndrome and other neurological disorders), and emerging data suggest that tandem repeat polymorphisms (TRPs) can also regulate gene expression in healthy individuals. TRPs in human genomes may also contribute to the missing heritability of polygenic disorders. A better understanding of tandem repeats and their associated repeatome, as well as their capacity for genetic plasticity via both germline and somatic mutations, is needed to transform our understanding of the role of TRPs in health and disease.}, } @article {pmid29398702, year = {2018}, author = {Wright, CF and FitzPatrick, DR and Firth, HV}, title = {Paediatric genomics: diagnosing rare disease in children.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {5}, pages = {253-268}, pmid = {29398702}, issn = {1471-0064}, abstract = {The majority of rare diseases affect children, most of whom have an underlying genetic cause for their condition. However, making a molecular diagnosis with current technologies and knowledge is often still a challenge. Paediatric genomics is an immature but rapidly evolving field that tackles this issue by incorporating next-generation sequencing technologies, especially whole-exome sequencing and whole-genome sequencing, into research and clinical workflows. This complex multidisciplinary approach, coupled with the increasing availability of population genetic variation data, has already resulted in an increased discovery rate of causative genes and in improved diagnosis of rare paediatric disease. Importantly, for affected families, a better understanding of the genetic basis of rare disease translates to more accurate prognosis, management, surveillance and genetic advice; stimulates research into new therapies; and enables provision of better support.}, } @article {pmid29398103, year = {2018}, author = {Monroe, JG and Markman, DW and Beck, WS and Felton, AJ and Vahsen, ML and Pressler, Y}, title = {Ecoevolutionary Dynamics of Carbon Cycling in the Anthropocene.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {213-225}, doi = {10.1016/j.tree.2017.12.006}, pmid = {29398103}, issn = {1872-8383}, mesh = {*Biological Evolution ; *Carbon Cycle ; *Climate Change ; *Ecosystem ; }, abstract = {Climate change is altering natural selection globally, which could shift the evolutionary trajectories of traits central to the carbon (C) cycle. Here, we examine the components necessary for the evolution of C cycling traits to substantially drive changes in global C cycling and integrate these components into a framework of ecoevolutionary dynamics. Recent evidence points to the evolution of C cycling traits during the Anthropocene and the potential to significantly affect atmospheric CO2. We identify directions for further collaboration between evolutionary, ecosystem, and climate scientists to study these ecoevolutionary feedback dynamics and determine whether this evolution will ultimately accelerate or decelerate the current trend in rising atmospheric CO2.}, } @article {pmid29398102, year = {2018}, author = {Harrison, JF}, title = {Reply to Glazier.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {238-239}, doi = {10.1016/j.tree.2018.01.004}, pmid = {29398102}, issn = {1872-8383}, } @article {pmid29398010, year = {2018}, author = {Escoubas, CC and Silva-García, CG and Mair, WB}, title = {Deregulation of CRTCs in Aging and Age-Related Disease Risk: (Trends in Genetics, 33, 303-321, 2017).}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {326}, doi = {10.1016/j.tig.2018.01.008}, pmid = {29398010}, issn = {0168-9525}, } @article {pmid29397878, year = {2018}, author = {De Castro, SCP and Hirst, CS and Savery, D and Rolo, A and Lickert, H and Andersen, B and Copp, AJ and Greene, NDE}, title = {Neural tube closure depends on expression of Grainyhead-like 3 in multiple tissues.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {130-137}, pmid = {29397878}, issn = {1095-564X}, support = {G0801124//Medical Research Council/United Kingdom ; J003794//Medical Research Council/United Kingdom ; 087525//Wellcome Trust/United Kingdom ; G080216//Medical Research Council/United Kingdom ; G0802163//Medical Research Council/United Kingdom ; }, mesh = {Animals ; DNA-Binding Proteins/deficiency/genetics/*physiology ; Embryonic Development ; Gene Expression Regulation, Developmental ; Genes, Reporter ; Germ Layers/metabolism ; Mice ; Mice, Knockout ; Mice, Transgenic ; Neural Plate/metabolism ; Neural Tube/*physiology ; Neural Tube Defects/embryology/*genetics/pathology ; Neurulation/*genetics ; Organ Specificity ; RNA, Messenger/biosynthesis ; Spinal Dysraphism/embryology/genetics ; Transcription Factors/deficiency/genetics/*physiology ; }, abstract = {Failure of neural tube closure leads to neural tube defects (NTDs), common congenital abnormalities in humans. Among the genes whose loss of function causes NTDs in mice, Grainyhead-like3 (Grhl3) is essential for spinal neural tube closure, with null mutants exhibiting fully penetrant spina bifida. During spinal neurulation Grhl3 is initially expressed in the surface (non-neural) ectoderm, subsequently in the neuroepithelial component of the neural folds and at the node-streak border, and finally in the hindgut endoderm. Here, we show that endoderm-specific knockout of Grhl3 causes late-arising spinal NTDs, preceded by increased ventral curvature of the caudal region which was shown previously to suppress closure of the spinal neural folds. This finding supports the hypothesis that diminished Grhl3 expression in the hindgut is the cause of spinal NTDs in the curly tail, carrying a hypomorphic Grhl3 allele. Complete loss of Grhl3 function produces a more severe phenotype in which closure fails earlier in neurulation, before the stage of onset of expression in the hindgut of wild-type embryos. This implicates additional tissues and NTD mechanisms in Grhl3 null embryos. Conditional knockout of Grhl3 in the neural plate and node-streak border has minimal effect on closure, suggesting that abnormal function of surface ectoderm, where Grhl3 transcripts are first detected, is primarily responsible for early failure of spinal neurulation in Grhl3 null embryos.}, } @article {pmid29397877, year = {2018}, author = {Roostalu, U and Wong, JK}, title = {Arterial smooth muscle dynamics in development and repair.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {109-121}, doi = {10.1016/j.ydbio.2018.01.018}, pmid = {29397877}, issn = {1095-564X}, support = {BB/M013170/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; MR/M007642/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Arteries/cytology/embryology/injuries/*physiology ; Biomarkers ; Cell Differentiation ; Gene Expression Regulation, Developmental ; Germ Layers/cytology ; Humans ; Intercellular Signaling Peptides and Proteins/physiology ; Intracellular Signaling Peptides and Proteins/physiology ; Mice ; Muscle, Smooth, Vascular/cytology/embryology/*physiology ; Myocytes, Smooth Muscle/physiology ; Neovascularization, Physiologic/*physiology ; Signal Transduction ; Transcription Factors/physiology ; Vasa Vasorum/physiology/ultrastructure ; Wound Healing/*physiology ; }, abstract = {Arterial vasculature distributes blood from early embryonic development and provides a nutrient highway to maintain tissue viability. Atherosclerosis, peripheral artery diseases, stroke and aortic aneurysm represent the most frequent causes of death and are all directly related to abnormalities in the function of arteries. Vascular intervention techniques have been established for the treatment of all of these pathologies, yet arterial surgery can itself lead to biological changes in which uncontrolled arterial wall cell proliferation leads to restricted blood flow. In this review we describe the intricate cellular composition of arteries, demonstrating how a variety of distinct cell types in the vascular walls regulate the function of arteries. We provide an overview of the developmental origin of arteries and perivascular cells and focus on cellular dynamics in arterial repair. We summarize the current knowledge of the molecular signaling pathways that regulate vascular smooth muscle differentiation in the embryo and in arterial injury response. Our review aims to highlight the similarities as well as differences between cellular and molecular mechanisms that control arterial development and repair.}, } @article {pmid29397208, year = {2018}, author = {Glazier, DS}, title = {Resource Supply and Demand Both Affect Metabolic Scaling: A Response to Harrison.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {4}, pages = {237-238}, doi = {10.1016/j.tree.2018.01.006}, pmid = {29397208}, issn = {1872-8383}, } @article {pmid29397203, year = {2018}, author = {Pek, JW}, title = {Stable Intronic Sequence RNAs Engage in Feedback Loops.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {330-332}, doi = {10.1016/j.tig.2018.01.006}, pmid = {29397203}, issn = {0168-9525}, mesh = {Animals ; Base Sequence/*genetics ; Conserved Sequence/genetics ; Drosophila melanogaster/genetics ; Gene Expression Regulation/genetics ; Introns/*genetics ; RNA/*genetics ; RNA Splicing/genetics ; RNA Stability/genetics ; RNA, Small Nucleolar/*genetics ; }, abstract = {Stable intronic sequence RNAs (sisRNAs) are conserved in various organisms. Recent observations in Drosophila suggest that sisRNAs often engage in regulatory feedback loops to control the expression of their parental genes. The use of sisRNAs as mediators for local feedback control may be a general phenomenon.}, } @article {pmid29396793, year = {2018}, author = {Orecchini, E and Frassinelli, L and Galardi, S and Ciafrè, SA and Michienzi, A}, title = {Post-transcriptional regulation of LINE-1 retrotransposition by AID/APOBEC and ADAR deaminases.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {1-2}, pages = {45-59}, pmid = {29396793}, issn = {1573-6849}, support = {GGP15227//Fondazione Telethon/International ; }, mesh = {APOBEC Deaminases/*metabolism ; Adenosine Deaminase/*metabolism ; Cytidine Deaminase/*metabolism ; DNA/metabolism ; Humans ; *Long Interspersed Nucleotide Elements ; RNA/metabolism ; RNA, Double-Stranded/metabolism ; *Retroelements ; }, abstract = {Long interspersed element-1 (LINE-1 or L1) retrotransposons represent the only functional family of autonomous transposable elements in humans and formed 17% of our genome. Even though most of the human L1 sequences are inactive, a limited number of copies per individual retain the ability to mobilize by a process termed retrotransposition. The ongoing L1 retrotransposition may result in insertional mutagenesis that could lead to negative consequences such as genetic disease and cancer. For this reason, cells have evolved several mechanisms of defense to restrict L1 activity. Among them, a critical role for cellular deaminases [activation-induced deaminase (AID)/apolipoprotein B mRNA-editing catalytic polypeptide-like (APOBEC) and adenosine deaminases that act on RNA (ADAR) enzymes] has emerged. The majority of the AID/APOBEC family of proteins are responsible for the deamination of cytosine to uracil (C-to-U editing) within DNA and RNA targets. The ADARs convert adenosine bases to inosines (A-to-I editing) within double-stranded RNA (dsRNA) targets. This review will discuss the current understanding of the regulation of LINE-1 retrotransposition mediated by these enzymes.}, } @article {pmid29396203, year = {2018}, author = {Prosser, C and Meyer, W and Ellis, J and Lee, R}, title = {Evolutionary ARMS Race: Antimalarial Resistance Molecular Surveillance.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {322-334}, doi = {10.1016/j.pt.2018.01.001}, pmid = {29396203}, issn = {1471-5007}, mesh = {Antimalarials/pharmacology/therapeutic use ; Drug Resistance/*genetics ; Drug Resistance, Multiple/genetics ; Humans ; Malaria/drug therapy/*parasitology/*prevention & control ; Plasmodium/drug effects/genetics ; Population Surveillance ; }, abstract = {Molecular surveillance of antimalarial drug resistance markers has become an important part of resistance detection and containment. In the current climate of multidrug resistance, including resistance to the global front-line drug artemisinin, there is a consensus to upscale molecular surveillance. The most salient limitation to current surveillance efforts is that skill and infrastructure requirements preclude many regions. This includes sub-Saharan Africa, where Plasmodium falciparum is responsible for most of the global malaria disease burden. New molecular and data technologies have emerged with an emphasis on accessibility. These may allow surveillance to be conducted in broad settings where it is most needed, including at the primary healthcare level in endemic countries, and extending to the village health worker.}, } @article {pmid29396202, year = {2018}, author = {Elsheikha, HM and Regan, CS and Clark, CG}, title = {Novel Entamoeba Findings in Nonhuman Primates.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {283-294}, doi = {10.1016/j.pt.2017.12.008}, pmid = {29396202}, issn = {1471-5007}, mesh = {Animals ; Biodiversity ; Entamoeba/*classification/cytology/genetics ; Entamoebiasis/*parasitology ; Primate Diseases/*parasitology ; Primates ; Species Specificity ; }, abstract = {In addition to well-known human-infecting species, Entamoeba species not found in humans have been identified recently in nonhuman primates (NHPs). Importantly, it has become clear that the organism identified as Entamoeba histolytica in NHPs is usually a distinct species, Entamoeba nuttalli. Many DNA-based stool surveys use species-specific detection methods and so may miss the full range of Entamoeba species present. In addition, authors may be using the same species name to describe distinct organisms. These various shortcomings may not be obvious to readers. In this review, we clarify the relationships between Entamoeba species' names based on morphological and molecular data, and highlight gaps in recently published data on Entamoeba species in wild NHPs resulting from the use of variable methodology.}, } @article {pmid29396201, year = {2018}, author = {Ritchie, SA and van den Hurk, AF and Smout, MJ and Staunton, KM and Hoffmann, AA}, title = {Mission Accomplished? We Need a Guide to the 'Post Release' World of Wolbachia for Aedes-borne Disease Control.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {217-226}, doi = {10.1016/j.pt.2017.11.011}, pmid = {29396201}, issn = {1471-5007}, mesh = {Aedes/*microbiology/*virology ; Animals ; Mosquito Vectors/*microbiology/*virology ; Pest Control, Biological/standards ; RNA Viruses/*physiology ; Wolbachia/*physiology ; }, abstract = {Historically, sustained control of Aedes aegypti, the vector of dengue, chikungunya, yellow fever, and Zika viruses, has been largely ineffective. Subsequently, two novel 'rear and release' control strategies utilizing mosquitoes infected with Wolbachia are currently being developed and deployed widely. In the incompatible insect technique, male Aedes mosquitoes, infected with Wolbachia, suppress populations through unproductive mating. In the transinfection strategy, both male and female Wolbachia-infected Ae. aegypti mosquitoes rapidly infect the wild population with Wolbachia, blocking virus transmission. It is critical to monitor the long-term stability of Wolbachia in host populations, and also the ability of this bacterium to continually inhibit virus transmission. Ongoing release and monitoring programs must be future-proofed should political support weaken when these vectors are successfully controlled.}, } @article {pmid29396200, year = {2018}, author = {, and Büscher, P and Bart, JM and Boelaert, M and Bucheton, B and Cecchi, G and Chitnis, N and Courtin, D and Figueiredo, LM and Franco, JR and Grébaut, P and Hasker, E and Ilboudo, H and Jamonneau, V and Koffi, M and Lejon, V and MacLeod, A and Masumu, J and Matovu, E and Mattioli, R and Noyes, H and Picado, A and Rock, KS and Rotureau, B and Simo, G and Thévenon, S and Trindade, S and Truc, P and Van Reet, N}, title = {Do Cryptic Reservoirs Threaten Gambiense-Sleeping Sickness Elimination?.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {197-207}, pmid = {29396200}, issn = {1471-5007}, support = {//Wellcome Trust/United Kingdom ; 001//World Health Organization/International ; 099310/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; *Disease Eradication ; *Disease Reservoirs ; Humans ; Risk Factors ; Trypanosoma brucei gambiense/physiology ; Trypanosomiasis, African/epidemiology/parasitology/*prevention & control/*transmission ; }, abstract = {Trypanosoma brucei gambiense causes human African trypanosomiasis (HAT). Between 1990 and 2015, almost 440000 cases were reported. Large-scale screening of populations at risk, drug donations, and efforts by national and international stakeholders have brought the epidemic under control with <2200 cases in 2016. The World Health Organization (WHO) has set the goals of gambiense-HAT elimination as a public health problem for 2020, and of interruption of transmission to humans for 2030. Latent human infections and possible animal reservoirs may challenge these goals. It remains largely unknown whether, and to what extend, they have an impact on gambiense-HAT transmission. We argue that a better understanding of the contribution of human and putative animal reservoirs to gambiense-HAT epidemiology is mandatory to inform elimination strategies.}, } @article {pmid29395731, year = {2018}, author = {Choudhury, BI and Whiteway, M}, title = {Evolutionary Transition of GAL Regulatory Circuit from Generalist to Specialist Function in Ascomycetes.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {692-702}, doi = {10.1016/j.tim.2017.12.008}, pmid = {29395731}, issn = {1878-4380}, abstract = {The Gal4 transcription factor (TF) controls gene expression by binding the DNA sequence motif CGG(N11)CCG. Well studied versions regulate metabolism of glucose in Candida albicans and galactose in Saccharomyces cerevisiae. Gal4 is also found within Aspergillus species and shows a wide range of potential binding targets. Members of the CTG clade that reassigned CUG codons from leucine to serine lack the Gal80 binding domain of Gal4, and they use the TF to regulate only glycolytic genes. In this clade, the galactose catabolic pathway (also known as the Leloir pathway) genes are regulated by Rtg1/Rtg3. In the WGD species, the complete Gal4/Gal80 module is limited to regulation of the Leloir pathway, while glycolysis is controlled by Gcr1/Gcr2. This shows a switch of Gal4 from a generalist to a specialist within the ascomycetes, and the split of glucose and galactose metabolism into distinct regulatory circuits.}, } @article {pmid29395730, year = {2018}, author = {Rolando, M and Buchrieser, C}, title = {Legionella Effectors Explored with INSeq: New Functional Insights.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {169-170}, doi = {10.1016/j.tim.2018.01.003}, pmid = {29395730}, issn = {1878-4380}, mesh = {*Bacterial Proteins ; *Legionella ; Legionella pneumophila ; }, abstract = {Legionella pneumophila secretes over 300 effector proteins that manipulate host cells. This multiplicity of effectors hampers the characterization of their individual roles. Shames et al. report a new approach to solve the enigma of Legionella effector function by using INSeq to analyse effector functions in the context of infection.}, } @article {pmid29395729, year = {2018}, author = {Samuel, GH and Adelman, ZN and Myles, KM}, title = {Antiviral Immunity and Virus-Mediated Antagonism in Disease Vector Mosquitoes.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {447-461}, pmid = {29395729}, issn = {1878-4380}, support = {R01 AI077726/AI/NIAID NIH HHS/United States ; R01 AI119081/AI/NIAID NIH HHS/United States ; }, mesh = {Adaptive Immunity ; Animals ; Antiviral Agents/*antagonists & inhibitors/*immunology ; Arbovirus Infections/*immunology/transmission/*veterinary ; Arboviruses/*immunology ; Chikungunya virus ; Culicidae/*immunology/virology ; Dengue Virus ; Encephalitis Virus, Japanese ; Host-Pathogen Interactions/immunology ; Humans ; MicroRNAs/metabolism ; Mosquito Vectors/*immunology/virology ; RNA Interference ; RNA, Small Interfering/metabolism ; Rift Valley fever virus ; Virus Replication/immunology ; Yellow fever virus ; Zika Virus ; }, abstract = {More than 100 pathogens, spanning multiple virus families, broadly termed 'arthropod-borne viruses (arboviruses)' have been associated with human and/or animal diseases. These viruses persist in nature through transmission cycles that involve alternating replication in susceptible vertebrate and invertebrate hosts. Collectively, these viruses are among the greatest burdens to global health, due to their widespread prevalence, and the severe morbidity and mortality they cause in human and animal hosts. Specific examples of mosquito-borne pathogens include Zika virus (ZIKV), West Nile virus (WNV), dengue virus serotypes 1-4 (DENV 1-4), Japanese encephalitis virus (JEV), yellow fever virus (YFV), chikungunya virus (CHIKV), and Rift Valley fever virus (RVFV). Interactions between arboviruses and the immune pathways of vertebrate hosts have been extensively reviewed. In this review we focus on the antiviral immune pathways present in mosquitoes. We also discuss mechanisms by which mosquito-borne viruses may antagonize antiviral pathways in disease vectors. Finally, we elaborate on the possibility that mosquito-borne viruses may be engaged in an evolutionary arms race with their invertebrate vector hosts, and the possible implications of this for understanding the transmission of mosquito-borne viruses.}, } @article {pmid29395728, year = {2018}, author = {Fernandez, J and Orth, K}, title = {Rise of a Cereal Killer: The Biology of Magnaporthe oryzae Biotrophic Growth.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {582-597}, pmid = {29395728}, issn = {1878-4380}, support = {T32 AI007520/AI/NIAID NIH HHS/United States ; }, abstract = {The rice blast fungus, Magnaporthe oryzae, causes one of the most destructive diseases of cultivated rice in the world. Infections caused by this recalcitrant pathogen lead to the annual destruction of approximately 10-30% of the rice harvested globally. The fungus undergoes extensive developmental changes to be able to break into plant cells, build elaborate infection structures, and proliferate inside host cells without causing visible disease symptoms. From a molecular standpoint, we are still in the infancy of understanding how M. oryzae manipulates the host during this complex multifaceted infection. Here, we describe recent advances in our understanding of the cell biology of M. oryzae biotrophic interaction and key molecular factors required for the disease establishment in rice cells.}, } @article {pmid29395513, year = {2018}, author = {Alexander, JM and Diez, JM and Usinowicz, J and Hart, SP}, title = {Species' Distributions as a Coexistence Problem: A Response to Godsoe et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {144-145}, doi = {10.1016/j.tree.2018.01.001}, pmid = {29395513}, issn = {1872-8383}, mesh = {*Ecosystem ; *Models, Biological ; Species Specificity ; }, } @article {pmid29395512, year = {2018}, author = {Chapron, G and Levrel, H and Meinard, Y and Courchamp, F}, title = {A Final Warning to Planet Earth.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {9}, pages = {651-652}, doi = {10.1016/j.tree.2017.12.010}, pmid = {29395512}, issn = {1872-8383}, } @article {pmid29395381, year = {2018}, author = {Blum, ID and Bell, B and Wu, MN}, title = {Time for Bed: Genetic Mechanisms Mediating the Circadian Regulation of Sleep.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {379-388}, pmid = {29395381}, issn = {0168-9525}, support = {R01 NS079584/NS/NINDS NIH HHS/United States ; R01 NS094571/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Circadian Clocks/*genetics/physiology ; Circadian Rhythm/*genetics/physiology ; Drosophila/genetics ; Humans ; Mice ; Neuronal Plasticity/*genetics/physiology ; Sleep/*genetics/physiology ; Zebrafish/genetics ; }, abstract = {Sleep is an evolutionarily conserved behavior that is increasingly recognized as important for human health. While its precise function remains controversial, sleep has been suggested to play a key role in a variety of biological phenomena ranging from synaptic plasticity to metabolic clearance. Although it is clear that sleep is regulated by the circadian clock, how this occurs remains enigmatic. Here we examine the genetic mechanisms by which the circadian clock regulates sleep, drawing on recent work in fruit flies, zebrafish, mice, and humans. These studies reveal that central and local clocks utilize diverse mechanisms to regulate different aspects of sleep, and a better understanding of this multilayered regulation may lead to a better understanding of the functions of sleep.}, } @article {pmid29395380, year = {2018}, author = {Schwartz, HT and Sternberg, PW}, title = {A Toolkit of Engineered Recombinational Balancers in C. elegans.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {253-255}, pmid = {29395380}, issn = {0168-9525}, support = {R24 OD023041/OD/NIH HHS/United States ; }, mesh = {Animals ; *CRISPR-Cas Systems ; Caenorhabditis elegans/*genetics ; Chromosomes ; Clustered Regularly Interspaced Short Palindromic Repeats ; }, abstract = {Dejima and colleagues report using CRISPR/Cas9 to generate a new collection of greatly improved balancer chromosomes in the standard laboratory nematode Caenorhabditis elegans, using methods previously reported by the same laboratory, expanding the set of C. elegans balancers to cover nearly 90% of coding genes.}, } @article {pmid29395379, year = {2018}, author = {Zelinger, L and Swaroop, A}, title = {RNA Biology in Retinal Development and Disease.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {341-351}, pmid = {29395379}, issn = {0168-9525}, support = {Z01 EY000450/EY/NEI NIH HHS/United States ; ZIA EY000450-09//NULL/International ; ZIA EY000546-02//NULL/International ; }, mesh = {Animals ; Computational Biology ; Gene Expression Profiling ; Gene Expression Regulation/*genetics ; Humans ; Neurons/metabolism/pathology ; RNA, Untranslated/*genetics ; Retina/*growth & development ; Retinal Diseases/*genetics/pathology ; }, abstract = {For decades, RNA has served in a supporting role between the genetic carrier (DNA) and the functional molecules (proteins). It is finally time for RNA to take center stage in all aspects of biology. The retina provides a unique opportunity to dissect the molecular underpinnings of neuronal diversity and disease. Transcriptome profiles of the retina and its resident cell types have unraveled unique features of the RNA landscape. The discovery of distinct RNA molecules and the recognition that RNA processing is a major cause of retinal neurodegeneration have prompted the design of biomarkers and novel therapeutic paradigms. We review here RNA biology as it pertains to the retina, emphasizing new avenues for investigations in development and disease.}, } @article {pmid29395378, year = {2018}, author = {Yang, MA and Fu, Q}, title = {Insights into Modern Human Prehistory Using Ancient Genomes.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {184-196}, doi = {10.1016/j.tig.2017.11.008}, pmid = {29395378}, issn = {0168-9525}, support = {55008731/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; DNA, Ancient/*analysis ; Evolution, Molecular ; Fossils ; Gene Flow ; *Genetic Variation ; Genome, Human/*genetics ; Hominidae/*genetics ; Humans ; Sequence Analysis, DNA ; }, abstract = {The genetic relationship of past modern humans to today's populations and each other was largely unknown until recently, when advances in ancient DNA sequencing allowed for unprecedented analysis of the genomes of these early people. These ancient genomes reveal new insights into human prehistory not always observed studying present-day populations, including greater details on the genetic diversity, population structure, and gene flow that characterized past human populations, particularly in early Eurasia, as well as increased insight on the relationship between archaic and modern humans. Here, we review genetic studies on ∼45000- to 7500-year-old individuals associated with mainly preagricultural cultures found in Eurasia, the Americas, and Africa.}, } @article {pmid29394957, year = {2018}, author = {Leung, MHY and Tong, X and Wilkins, D and Cheung, HHL and Lee, PKH}, title = {Individual and household attributes influence the dynamics of the personal skin microbiota and its association network.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {26}, pmid = {29394957}, issn = {2049-2618}, support = {11211815//Research Grants Council of Hong Kong/International ; }, mesh = {Acinetobacter/classification/genetics/isolation & purification ; Bacillus/classification/genetics/isolation & purification ; Bacteria/*classification/genetics/isolation & purification ; Biodiversity ; Family Characteristics ; Female ; Host Specificity ; Humans ; Male ; Microbiota ; Phylogeny ; Propionibacterium/classification/genetics/isolation & purification ; Seasons ; Sequence Analysis, DNA/*methods ; Skin/*microbiology ; Urban Population ; }, abstract = {BACKGROUND: Numerous studies have thus far characterized the temporal dynamics of the skin microbiota of healthy individuals. However, there is no information regarding the dynamics of different microbial association network properties. Also, there is little understanding of how living conditions, specifically cohabitation and household occupancy, may be associated with the nature and extent (or degree) of cutaneous microbiota change within individuals over time. In this study, the dynamics of the skin microbiota, and its association networks, on the skin of urban residents over four seasons were characterized.

RESULTS: Similar to western cohorts, the individuals of this cohort show different extents of variations in relative abundance of common skin colonizers, concomitant with individual- and household-associated changes in differential abundances of bacterial taxa. Interestingly, the individualized nature of the skin microbiota extends to various aspects of microbial association networks, including co-occurring and excluding taxa, as well as overall network structural properties. Household occupancy is correlated with the extent of variations in relative abundance of Propionibacterium, Acinetobacter, and Bacillus over multiple skin sites. In addition, household occupancy is also associated with the extent of temporal changes in microbial diversity and composition within a resident's skin.

CONCLUSIONS: This is the first study investigating the potential roles household occupancy has on the extent of change in one's cutaneous microbiota and its association network structures. In particular, we show that relationships between the skin microbiota of a resident, his/her cohabitants, and those of non-cohabitants over time are highly personal and are possibly governed by living conditions and nature of interactions between cohabitants within households over 1 year. This study calls for increased awareness to personal and lifestyle factors that may govern relationships between the skin microbiota of one individual and those of cohabitants, and changes in the microbial association network structures within a person over time. The current study will act as a baseline for future assessments in comparing against temporal dynamics of microbiota from individuals with different skin conditions and for identifying residential factors that are beneficial in promoting the dynamics of the skin microbiota associated with health.}, } @article {pmid29394954, year = {2018}, author = {Hyytiäinen, HK and Jayaprakash, B and Kirjavainen, PV and Saari, SE and Holopainen, R and Keskinen, J and Hämeri, K and Hyvärinen, A and Boor, BE and Täubel, M}, title = {Crawling-induced floor dust resuspension affects the microbiota of the infant breathing zone.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {25}, pmid = {29394954}, issn = {2049-2618}, support = {296814//Suomen Akatemia/International ; 201710468//Juho Vainion Säätiö/International ; F13D10740//U.S. Environmental Protection Agency/International ; }, mesh = {*Air Microbiology ; Air Pollution, Indoor/analysis ; Bacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Fungal/genetics ; DNA, Ribosomal/genetics ; Dust/*analysis ; Environmental Monitoring ; Floors and Floorcoverings ; Fungi/*classification/genetics/isolation & purification ; Humans ; Infant ; Microbiota ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Floor dust is commonly used for microbial determinations in epidemiological studies to estimate early-life indoor microbial exposures. Resuspension of floor dust and its impact on infant microbial exposure is, however, little explored. The aim of our study was to investigate how floor dust resuspension induced by an infant's crawling motion and an adult walking affects infant inhalation exposure to microbes.

RESULTS: We conducted controlled chamber experiments with a simplified mechanical crawling infant robot and an adult volunteer walking over carpeted flooring. We applied bacterial 16S rRNA gene sequencing and quantitative PCR to monitor the infant breathing zone microbial content and compared that to the adult breathing zone and the carpet dust as the source. During crawling, fungal and bacterial levels were, on average, 8- to 21-fold higher in the infant breathing zone compared to measurements from the adult breathing zone. During walking experiments, the increase in microbial levels in the infant breathing zone was far less pronounced. The correlation in rank orders of microbial levels in the carpet dust and the corresponding infant breathing zone sample varied between different microbial groups but was mostly moderate. The relative abundance of bacterial taxa was characteristically distinct in carpet dust and infant and adult breathing zones during the infant crawling experiments. Bacterial diversity in carpet dust and the infant breathing zone did not correlate significantly.

CONCLUSIONS: The microbiota in the infant breathing zone differ in absolute quantitative and compositional terms from that of the adult breathing zone and of floor dust. Crawling induces resuspension of floor dust from carpeted flooring, creating a concentrated and localized cloud of microbial content around the infant. Thus, the microbial exposure of infants following dust resuspension is difficult to predict based on common house dust or bulk air measurements. Improved approaches for the assessment of infant microbial exposure, such as sampling at the infant breathing zone level, are needed.}, } @article {pmid29394889, year = {2018}, author = {Tu, X and Liu, Z and Zhang, Z}, title = {Comparative transcriptomic analysis of resistant and susceptible alfalfa cultivars (Medicago sativa L.) after thrips infestation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {116}, pmid = {29394889}, issn = {1471-2164}, support = {CARS-34-07B//This research was funded by the China Agriculture Research System, P.R. China./International ; }, mesh = {Animals ; Disease Resistance/*genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Plant ; Medicago sativa/*genetics/parasitology ; Plant Diseases/*genetics/parasitology ; Plant Proteins/*genetics ; RNA, Messenger/genetics ; Salicylic Acid/metabolism ; Signal Transduction ; Thysanoptera/*physiology ; *Transcriptome ; }, abstract = {BACKGROUND: Plant breeding for resistance to agricultural pests is an essential element in the development of integrated crop management systems; however, the molecular and genetic mechanisms underlying resistance are poorly understood. In this pilot study, a transcriptomic analysis of a resistant (R) vs. a susceptible (S) variety of alfalfa, with (+T) or without (-T) thrips (= 4 treatments) was conducted, 'GN-1' (China) was defined as the resistant cultivar, and 'WL323' (America) was defined as the susceptible cultivar.

RESULTS: A total of 970 mRNAs were differentially expressed, of which 129 up- and 191 down-regulated genes were identified in the R + T/R-T plants, while 413 up- and 237 down-regulated genes were identified in the S + T/S-T plants. KEGG analysis mapped 33 and 80 differentially expressed genes to 11 and 14 substantially enriched pathways for GN-1 and WL323, respectively. Five shared pathways were linked to plant resistance traits, including beta-Alanine metabolism, fatty acid degradation, chloroalkane and chloroalkene degradation, flavonoid biosynthesis, and phenylalanine metabolism.

CONCLUSIONS: Results indicated both thrips resistant and susceptible alfalfa cultivars can regulate gene expression in the salicylic acid (SA) and flavonoid biosynthesis pathways to induce defensive genes and protein expression (e.g. polyphenol oxidase, protease inhibitor), which enhances plant defence capacity.}, } @article {pmid29394882, year = {2018}, author = {Zhu, L and Shahid, MA and Markham, J and Browning, GF and Noormohammadi, AH and Marenda, MS}, title = {Genome analysis of Mycoplasma synoviae strain MS-H, the most common M. synoviae strain with a worldwide distribution.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {117}, pmid = {29394882}, issn = {1471-2164}, mesh = {Animals ; Bacterial Proteins/*genetics ; Bacterial Vaccines/*genetics ; Chickens/microbiology ; Chromosome Inversion ; Genetic Markers ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; Mycoplasma Infections/microbiology/prevention & control/*veterinary ; Mycoplasma synoviae/*genetics ; Poultry Diseases/microbiology/*prevention & control ; Sequence Analysis, DNA ; Vaccines, Attenuated/genetics ; }, abstract = {BACKGROUND: The bacterial pathogen Mycoplasma synoviae can cause subclinical respiratory disease, synovitis, airsacculitis and reproductive tract disease in poultry and is a major cause of economic loss worldwide. The M. synoviae strain MS-H was developed by chemical mutagenesis of an Australian isolate and has been used as a live attenuated vaccine in many countries over the past two decades. As a result it may now be the most prevalent strain of M. synoviae globally. Differentiation of the MS-H vaccine from local field strains is important for epidemiological investigations and is often required for registration of the vaccine.

RESULTS: The complete genomic sequence of the MS-H strain was determined using a combination of Illumina and Nanopore methods and compared to WVU-1853, the M. synoviae type strain isolated in the USA 30 years before the parent strain of MS-H, and MS53, a more recent isolate from Brazil. The vaccine strain genome had a slightly larger number of pseudogenes than the two other strains and contained a unique 55 kb chromosomal inversion partially affecting a putative genomic island. Variations in gene content were also noted, including a deoxyribose-phosphate aldolase (deoC) fragment and an ATP-dependent DNA helicase gene found only in MS-H. Some of these sequences may have been acquired horizontally from other avian mycoplasma species.

CONCLUSIONS: MS-H was somewhat more similar to WVU-1853 than to MS53. The genome sequence of MS-H will enable identification of vaccine-specific genetic markers for use as diagnostic and epidemiological tools to better control M. synoviae.}, } @article {pmid29394881, year = {2018}, author = {Windsor Reid, PJ and Matveev, E and McClymont, A and Posfai, D and Hill, AL and Leys, SP}, title = {Wnt signaling and polarity in freshwater sponges.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {12}, pmid = {29394881}, issn = {1471-2148}, support = {0829763//National Science Foundation/International ; 52007567/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; *Fresh Water ; Gene Expression Regulation ; Glycogen Synthase Kinase 3/genetics ; Larva/genetics ; Phylogeny ; Porifera/genetics/*metabolism ; RNA Interference ; Wnt Proteins/genetics/metabolism ; *Wnt Signaling Pathway/genetics ; beta Catenin/metabolism ; }, abstract = {BACKGROUND: The Wnt signaling pathway is uniquely metazoan and used in many processes during development, including the formation of polarity and body axes. In sponges, one of the earliest diverging animal groups, Wnt pathway genes have diverse expression patterns in different groups including along the anterior-posterior axis of two sponge larvae, and in the osculum and ostia of others. We studied the function of Wnt signaling and body polarity formation through expression, knockdown, and larval manipulation in several freshwater sponge species.

RESULTS: Sponge Wnts fall into sponge-specific and sponge-class specific subfamilies of Wnt proteins. Notably Wnt genes were not found in transcriptomes of the glass sponge Aphrocallistes vastus. Wnt and its signaling genes were expressed in archaeocytes of the mesohyl throughout developing freshwater sponges. Osculum formation was enhanced by GSK3 knockdown, and Wnt antagonists inhibited both osculum development and regeneration. Using dye tracking we found that the posterior poles of freshwater sponge larvae give rise to tissue that will form the osculum following metamorphosis.

CONCLUSIONS: Together the data indicate that while components of canonical Wnt signaling may be used in development and maintenance of osculum tissue, it is likely that Wnt signaling itself occurs between individual cells rather than whole tissues or structures in freshwater sponges.}, } @article {pmid29394416, year = {2018}, author = {Rodrigues, N and Studer, T and Dufresnes, C and Perrin, N}, title = {Sex-Chromosome Recombination in Common Frogs Brings Water to the Fountain-of-Youth.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {942-948}, doi = {10.1093/molbev/msy008}, pmid = {29394416}, issn = {1537-1719}, abstract = {According to the canonical model of sex-chromosome evolution, the degeneration of Y or W chromosomes (as observed in mammals and birds, respectively) results from an arrest of recombination in the heterogametic sex, driven by the fixation of sexually antagonistic mutations. However, sex chromosomes have remained homomorphic in many lineages of fishes, amphibians, and nonavian reptiles. According to the "fountain-of-youth" model, this homomorphy results from occasional events of sex reversal. If recombination arrest in males is controlled by maleness per se (and not by genotype), then Y chromosomes are expected to recombine in XY females, preventing their long-term degeneration. Here, we provide field support for the fountain-of-youth, by showing that sex-chromosome recombination in Rana temporaria only depends on phenotypic sex: naturally occurring XX males show the same restriction of recombination as XY males (average map length ∼2 cM), while XY females recombine as much as XX females (average map length ∼150 cM). Our results challenge several common assumptions regarding the evolution of sex chromosomes, including the role of sexually antagonistic genes as drivers of recombination arrest, and that of chromosomal inversions as underlying mechanisms.}, } @article {pmid29394344, year = {2018}, author = {Tek, EL and Sundstrom, JF and Gardner, JM and Oliver, SG and Jiranek, V}, title = {Evaluation of the ability of commercial wine yeasts to form biofilms (mats) and adhere to plastic: implications for the microbiota of the winery environment.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix188}, pmid = {29394344}, issn = {1574-6941}, abstract = {Commercially available active dried wine yeasts are regularly used by winemakers worldwide to achieve reliable fermentations and obtain quality wine. This practice has led to increased evidence of traces of commercial wine yeast in the vineyard, winery and uninoculated musts. The mechanism(s) that enables commercial wine yeast to persist in the winery environment and the influence to native microbial communities on this persistence is poorly understood. This study has investigated the ability of commercial wine yeasts to form biofilms and adhere to plastic. The results indicate that the biofilms formed by commercial yeasts consist of cells with a combination of different lifestyles (replicative and non-replicative) and growth modes including invasive growth, bud elongation, sporulation and a mat sectoring-like phenotype. Invasive growth was greatly enhanced on grape pulp regardless of strain, while adhesion on plastic varied between strains. The findings suggest a possible mechanism that allows commercial yeast to colonise and survive in the winery environment, which may have implications for the indigenous microbiota profile as well as the population profile in uninoculated fermentations if their dissemination is not controlled.}, } @article {pmid29394096, year = {2018}, author = {Berner, N and Reutter, KR and Wolf, DH}, title = {Protein Quality Control of the Endoplasmic Reticulum and Ubiquitin-Proteasome-Triggered Degradation of Aberrant Proteins: Yeast Pioneers the Path.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {751-782}, doi = {10.1146/annurev-biochem-062917-012749}, pmid = {29394096}, issn = {1545-4509}, abstract = {Cells must constantly monitor the integrity of their macromolecular constituents. Proteins are the most versatile class of macromolecules but are sensitive to structural alterations. Misfolded or otherwise aberrant protein structures lead to dysfunction and finally aggregation. Their presence is linked to aging and a plethora of severe human diseases. Thus, misfolded proteins have to be rapidly eliminated. Secretory proteins constitute more than one-third of the eukaryotic proteome. They are imported into the endoplasmic reticulum (ER), where they are folded and modified. A highly elaborated machinery controls their folding, recognizes aberrant folding states, and retrotranslocates permanently misfolded proteins from the ER back to the cytosol. In the cytosol, they are degraded by the highly selective ubiquitin-proteasome system. This process of protein quality control followed by proteasomal elimination of the misfolded protein is termed ER-associated degradation (ERAD), and it depends on an intricate interplay between the ER and the cytosol.}, } @article {pmid29393586, year = {2018}, author = {Ueno, Y and Yoshida, E and Misumi, W and Watando, E and Suzuki, K and Hirai, Y and Okura, M and Osaki, M and Katsuda, K and Takamatsu, D}, title = {Population structure and antimicrobial susceptibility of Paenibacillus larvae isolates from American foulbrood cases in Apis mellifera in Japan.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {210-216}, doi = {10.1111/1758-2229.12623}, pmid = {29393586}, issn = {1758-2229}, mesh = {Animals ; Anti-Bacterial Agents/*pharmacology ; Bees/*microbiology ; Genetic Variation ; Genotype ; Japan ; Multilocus Sequence Typing ; Paenibacillus larvae/classification/*drug effects/genetics/*isolation & purification ; Polymerase Chain Reaction ; United States ; }, abstract = {Paenibacillus larvae is the causative agent of American foulbrood (AFB), the most destructive disease of the honey bee brood. In this study, we investigated the population structure and antimicrobial susceptibility of Japanese P. larvae using 100 isolates isolated between 1993 and 2017 in 17 prefectures. Using repetitive-element PCR and multilocus sequence typing, isolates from diverse origins were classified into six genotypes, including the novel genotype ERIC II-ST24. Among these genotypes, ERIC I-ST15 is the most common in Japan, while ERIC II-ST10 isolates were found to be increasing during the 2010s. Regardless of genotype or origin, all isolates were susceptible to the major antimicrobials used in the control of AFB, including mirosamicin and tylosin, which were approved for the prevention of AFB in Japan in 1999 and 2017 respectively. Despite nearly 20 years of use, mirosamicin is still effective against Japanese P. larvae in vitro; however, the development of AFB in honey bee colonies may not always be suppressed by this drug. The case information collected in this study provides insight into the conditions under which prophylactic medicine may not exert sufficient preventive effects in vivo.}, } @article {pmid29393582, year = {2018}, author = {Zimmermann, M and Escrig, S and Lavik, G and Kuypers, MMM and Meibom, A and Ackermann, M and Schreiber, F}, title = {Substrate and electron donor limitation induce phenotypic heterogeneity in different metabolic activities in a green sulphur bacterium.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {179-183}, doi = {10.1111/1758-2229.12616}, pmid = {29393582}, issn = {1758-2229}, mesh = {Chlorobium/classification/genetics/isolation & purification/*metabolism ; Electron Transport ; Hydrogen Sulfide/*metabolism ; Nitrogen Fixation ; Phenotype ; Spectrometry, Mass, Secondary Ion ; Sulfur/*metabolism ; }, abstract = {Populations of genetically identical cells can display marked variation in phenotypic traits; such variation is termed phenotypic heterogeneity. Here, we investigate the effect of substrate and electron donor limitation on phenotypic heterogeneity in N2 and CO2 fixation in the green sulphur bacterium Chlorobium phaeobacteroides. We grew populations in chemostats and batch cultures and used stable isotope labelling combined with nanometer-scale secondary ion mass spectrometry (NanoSIMS) to quantify phenotypic heterogeneity. Experiments in H2 S (i.e. electron donor) limited chemostats show that varying levels of NH4+ limitation induce heterogeneity in N2 fixation. Comparison of phenotypic heterogeneity between chemostats and batch (unlimited for H2 S) populations indicates that electron donor limitation drives heterogeneity in N2 and CO2 fixation. Our results demonstrate that phenotypic heterogeneity in a certain metabolic activity can be driven by different modes of limitation and that heterogeneity can emerge in different metabolic processes upon the same mode of limitation. In conclusion, our data suggest that limitation is a general driver of phenotypic heterogeneity in microbial populations.}, } @article {pmid29393577, year = {2018}, author = {Mariappan, V and Thimma, J and Vellasamy, KM and Shankar, EM and Vadivelu, J}, title = {Adhesion and invasion attributes of Burkholderia pseudomallei are dependent on airway surface liquid and glucose concentrations in lung epithelial cells.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {217-225}, doi = {10.1111/1758-2229.12624}, pmid = {29393577}, issn = {1758-2229}, mesh = {*Bacterial Adhesion ; Burkholderia pseudomallei/genetics/pathogenicity/*physiology ; Epithelial Cells/*metabolism/microbiology ; Glucose/*metabolism ; Humans ; Lung/*metabolism/microbiology ; Melioidosis/*metabolism/microbiology ; Virulence ; }, abstract = {Physiological constituents in airway surface liquids (ASL) appear to impact the adherence and invasion potentials of Burkholderia pseudomallei contributing to recrudescent melioidosis. Here, we investigated the factors present in ASL that is likely to influence bacterial adhesion and invasion leading to improved understanding of bacterial pathogenesis. Six B. pseudomallei clinical isolates from different origins were used to investigate the ability of the bacteria to adhere and invade A549 human lung epithelial cells using a system that mimics the physiological ASL with different pH, NaCl, KCl, CaCl2 and glucose concentrations. These parameters resulted in markedly differential adherence and invasion abilities of B. pseudomallei to the lung epithelial cells. The concentration of 20 mM glucose dramatically increased adherence and invasion by increasing the rate of pili formation in depiliated bacteria. Glucose significantly increased adherence and invasion of B. pseudomallei to A549 cells, and presence of NaCl, KCl and CaCl2 markedly ablated the effect despite the presence of glucose. Our data established a link between glucose, enhanced adhesion and invasion potentials of B. pseudomallei, hinting increased susceptibility of individuals with diabetes mellitus to clinical melioidosis.}, } @article {pmid29393575, year = {2018}, author = {Diogo, R}, title = {Where is, in 2017, the evo in evo-devo (evolutionary developmental biology)?.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {1}, pages = {15-22}, doi = {10.1002/jez.b.22791}, pmid = {29393575}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; *Developmental Biology ; Interdisciplinary Research ; Models, Biological ; }, abstract = {After the inaugural Pan-American-Evo-Devo meeting (2015, Berkeley), I showed how major concerns about evo-devo (Evolutionary Developmental Biology) research were demonstrated by a simple, non-biased quantitative analysis of the titles/abstracts of that meeting's talks. Here, I apply the same methodology to the titles/abstracts of the recent Pan-American-Evo-Devo meeting (2017, Calgary). The aim is to evaluate if the concerns raised by me in that paper and by other authors have been addressed and/or if there are other types of differences between the two meetings that may reflect trends within the field of evo-devo. This analysis shows that the proportion of presentations referring to "morphology", "organism", "selection", "adaptive", "phylogeny", and their derivatives was higher in the 2017 meeting, which therefore had a more "organismal" feel. However, there was a decrease in the use of "evolution"/its derivatives and of macroevolutionary terms related to the tempo and mode of evolution in the 2017 meeting. Moreover, the disproportionately high use of genetic/genomic terms clearly shows that evo-devo continues to be mainly focused on devo, and particularly on "Geno", that is, on molecular/genetic studies. Furthermore, the vast majority of animal evo-devo studies are focused only on hard tissues, which are just a small fraction of the whole organism-for example, only 15% of the tissue mass of the human body. The lack of an integrative approach is also evidenced by the lack of studies addressing conceptual/long-standing broader questions, including the links between ecology and particularly behavior and developmental/evolutionary variability and between evo-devo and evolutionary medicine.}, } @article {pmid29393573, year = {2018}, author = {Bouillet, S and Arabet, D and Jourlin-Castelli, C and Méjean, V and Iobbi-Nivol, C}, title = {Regulation of σ factors by conserved partner switches controlled by divergent signalling systems.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {127-139}, doi = {10.1111/1758-2229.12620}, pmid = {29393573}, issn = {1758-2229}, mesh = {Bacteria/classification/*enzymology/genetics ; Bacterial Proteins/genetics/*metabolism ; *Gene Expression Regulation, Bacterial ; Phosphoric Monoester Hydrolases/genetics/*metabolism ; Phylogeny ; Sigma Factor/genetics/*metabolism ; *Signal Transduction ; }, abstract = {Partner-Switching Systems (PSS) are widespread regulatory systems, each comprising a kinase-anti-σ, a phosphorylatable anti-σ antagonist and a phosphatase module. The anti-σ domain quickly sequesters or delivers the target σ factor according to the phosphorylation state of the anti-σ antagonist induced by environmental signals. The PSS components are proteins alone or merged to other domains probably to adapt to the input signals. PSS are involved in major cellular processes including stress response, sporulation, biofilm formation and pathogenesis. Surprisingly, the target σ factors are often unknown and the sensing modules acting upstream from the PSS diverge according to the bacterial species. Indeed, they belong to either two-component systems or complex pathways as the stressosome or Chemosensory Systems (CS). Based on a phylogenetic analysis, we propose that the sensing module in Gram-negative bacteria is often a CS.}, } @article {pmid29393572, year = {2018}, author = {Hüttener, M and Prieto, A and Aznar, S and Dietrich, M and Paytubi, S and Juárez, A}, title = {Tetracycline alters gene expression in Salmonella strains that harbor the Tn10 transposon.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {202-209}, doi = {10.1111/1758-2229.12621}, pmid = {29393572}, issn = {1758-2229}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/*genetics/metabolism ; *DNA Transposable Elements ; Operon/drug effects ; Plasmids/genetics/metabolism ; Salmonella/*drug effects/*genetics/metabolism ; Tetracycline/*pharmacology ; }, abstract = {In this report, we show that bacterial plasmids that harbor the Tn10 transposon (i.e., the IncHI1 plasmid R27) modify expression of different Salmonella regulons responding to the presence of tetracycline (Tc) in the medium. By using as a model the Tc-dependent upregulation of the ibpAB operon (which belongs to the heat shock regulon), we have identified Tn10-tetA (coding for a Tc efflux pump) and adjacent tetC sequences as required for ibpAB upregulation. Characterization of transcripts in the tetAC region showed that tetA transcription can continue into tetC sequences, generating a long 3'UTR sequence, which can protect transcripts from RNA processing, thus increasing the expression of TetA protein. In the presence of Tc, the DnaK and IbpA chaperones are overexpressed and translocated to the periplasm and to the membrane fraction respectively. DnaK targeting unfolded proteins is known to induce heat shock by avoiding RpoH proteolysis. We correlate expression levels of Tn10-encoded TetA protein with heat shock induction in Salmonella, likely because TetA activity compromises protein secretion.}, } @article {pmid29393571, year = {2018}, author = {van der Meer, JM}, title = {RNase reverses segment sequence in the anterior of a beetle egg (Callosobruchus maculatus, Coleoptera).}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {1}, pages = {52-59}, doi = {10.1002/jez.b.22789}, pmid = {29393571}, issn = {1552-5015}, mesh = {Animals ; Body Patterning/genetics/physiology ; Coleoptera/*embryology/*genetics ; Embryo, Nonmammalian ; Embryonic Development ; Gene Expression Regulation, Developmental/physiology ; Insect Proteins/genetics/*metabolism ; RNA, Messenger ; Ribonucleases/*metabolism ; }, abstract = {The genetic regulation of anterior-posterior segment pattern development has been elucidated in detail for Drosophila, but it is not canonical for insects. A surprising diversity of regulatory mechanisms is being uncovered not only between insect orders, but also within the order of the Diptera. The question is whether the same diversity of regulatory mechanisms exists within other insect orders. I show that anterior puncture of the egg of the pea beetle Callosobruchus maculatus submerged in RNase can induce double abdomen development suggesting a role for maternal mRNA. In a double abdomen, anterior segments are replaced by posterior segments oriented in mirror image symmetry to the original posterior segments. This effect is specific for RNase activity, for treatment of the anterior egg pole and for cytoplasmic RNA. Yield depends on developmental stage, enzyme concentration, and temperature. A maximum of 30% of treated eggs reversed segment sequence after submersion and puncture in 10 μg/mL RNase S reconstituted from S-protein and S-peptide at 30°C. This result sets the stage for an analysis of the genetic regulation of segment pattern formation in the long germ embryo of the coleopteran Callosobruchus and for comparison with the short germ embryo of the coleopteran Tribolium.}, } @article {pmid29393570, year = {2018}, author = {Punzi, E and Milani, L and Ghiselli, F and Passamonti, M}, title = {Lose it or keep it: (how bivalves can provide) insights into mitochondrial inheritance mechanisms.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {1}, pages = {41-51}, doi = {10.1002/jez.b.22788}, pmid = {29393570}, issn = {1552-5015}, mesh = {Animals ; Bivalvia/*genetics ; Mitochondria/*genetics ; Transcriptome ; Ubiquitin-Protein Ligases/*genetics/metabolism ; }, abstract = {The strictly maternal inheritance (SMI) is a pattern of mitochondrial inheritance observed across the whole animal kingdom. However, some interesting exceptions are known for the class Bivalvia, in which several species show an unusual pattern called doubly uniparental inheritance (DUI) whose outcome is a heteroplasmic pool of mtDNA in males. Even if DUI has been studied for long, its molecular basis has not been established yet. The aim of this work is to select classes of proteins known to be involved in the maintenance of SMI and to compare their features in two clam species differing for their mitochondrial inheritance mechanism, that is, the SMI species Ruditapes decussatus and the DUI species Ruditapes philippinarum. Data have been obtained from the transcriptomes of male and female ripe gonads of both species. Our analysis focused on nucleases and polymerases, ubiquitination and ubiquitin-like modifier pathways, and proteins involved in autophagy and mitophagy. For each protein group of interest, transcription bias (male or female), annotation, and mitochondrial targeting (when appropriate) were assessed. We did not find evidence supporting a role of nucleases/polymerases or autophagic machinery in the enforcement of SMI in R. decussatus. On the other hand, ubiquitinating enzymes with the expected features have been retrieved, providing us with two alternative testable models for mitochondrial inheritance mechanisms at the molecular level.}, } @article {pmid29393568, year = {2018}, author = {Shen, D and Jürgens, K and Beier, S}, title = {Experimental insights into the importance of ecologically dissimilar bacteria to community assembly along a salinity gradient.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1170-1184}, doi = {10.1111/1462-2920.14059}, pmid = {29393568}, issn = {1462-2920}, abstract = {The response of local communities to marine-freshwater transitions and the processes that underlie community assembly are unclear, particularly with respect to bacteria that differ in their life strategies. Here, we implemented a transplant experiment where bacterioplankton from three regions of the Baltic Sea with differing salinities (∼3, 7 and 28 psu) were exposed to each other's environmental conditions. We found that habitat specialists were more abundant than generalists after exposure to salinity changes, irrespective of their origins. Most specialists that were selected following a salinity change were rare in the starting communities. Selection for generalists, however, was not specifically driven by the recruitment of either rare or abundant members, suggesting that taxon's initial abundance is minor relevant to the growth of generalists. Patterns in phylogenetic relatedness indicated that environmental filtering was the most influential assembly mechanism for specialists, whereas competitive interaction was more important for the assembly of generalists. Altogether, this study shows that large salinity changes promote the establishment of habitat specialists and that deterministic processes vary during community assembly for ecologically dissimilar taxa. We, therefore, propose that distinguishing assembly mechanisms of different community members helps understand and predict community dynamics in response to environmental change.}, } @article {pmid29393565, year = {2018}, author = {Chowdhary, A and Meis, JF}, title = {Emergence of azole resistant Aspergillus fumigatus and One Health: time to implement environmental stewardship.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1299-1301}, doi = {10.1111/1462-2920.14055}, pmid = {29393565}, issn = {1462-2920}, } @article {pmid29393562, year = {2018}, author = {Zhu, X and Jiao, M and Guo, J and Liu, P and Tan, C and Yang, Q and Zhang, Y and Thomas Voegele, R and Kang, Z and Guo, J}, title = {A novel MADS-box transcription factor PstMCM1-1 is responsible for full virulence of Puccinia striiformis f. sp. tritici.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1452-1463}, doi = {10.1111/1462-2920.14054}, pmid = {29393562}, issn = {1462-2920}, abstract = {In many eukaryotes, transcription factor MCM1 gene plays crucial roles in regulating mating processes and pathogenesis by interacting with other co-factors. However, little is known about the role of MCM1 in rust fungi. Here, we identified two MCM1 orthologs, PstMCM1-1 and PstMCM1-2, in the stripe rust pathogen Puccinia striiformis f. sp. tritici (Pst). Sequence analysis indicated that both PstMCM1-1 and PstMCM1-2 contain conserved MADS domains and that PstMCM1-1 belongs to a group of SRF-like proteins that are evolutionarily specific to rust fungi. Yeast two-hybrid assays indicated that PstMCM1-1 interacts with transcription factors PstSTE12 and PstbE1. PstMCM1-1 was found to be highly induced during early infection stages in wheat and during pycniospore formation on the alternate host barberry (Berberis shensiana). PstMCM1-1 could complement the lethal phenotype and mating defects in a mcm1 mutant of Saccharomyces cerevisiae. In addition, it partially complemented the defects in appressorium formation and plant infection in a Magnaporthe oryzae Momcm1 mutant. Knock down of PstMCM1-1 resulted in a significant reduction of hyphal extension and haustorium formation and the virulence of Pst on wheat. Our results suggest that PstMCM1-1 plays important roles in the regulation of mating and pathogenesis of Pst most likely by interacting with co-factors.}, } @article {pmid29393559, year = {2018}, author = {Michalik, A and Schulz, F and Michalik, K and Wascher, F and Horn, M and Szklarzewicz, T}, title = {Coexistence of novel gammaproteobacterial and Arsenophonus symbionts in the scale insect Greenisca brachypodii (Hemiptera, Coccomorpha: Eriococcidae).}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1148-1157}, doi = {10.1111/1462-2920.14057}, pmid = {29393559}, issn = {1462-2920}, abstract = {Scale insects are commonly associated with obligate, intracellular microorganisms which play important roles in complementing their hosts with essential nutrients. Here we characterized the symbiotic system of Greenisca brachypodii, a member of the family Eriococcidae. Histological and ultrastructural analyses have indicated that G. brachypodii is stably associated with coccoid and rod-shaped bacteria. Phylogenetic analyses have revealed that the coccoid bacteria represent a sister group to the secondary symbiont of the mealybug Melanococcus albizziae, whereas the rod-shaped symbionts are close relatives of Arsenophonus symbionts in insects - to our knowledge, this is the first report of the presence of Arsenophonus bacterium in scale insects. As a comparison of 16S and 23S rRNA genes sequences of the G. brachypodii coccoid symbiont with other gammaprotebacterial sequences showed only low similarity (∼90%), we propose the name 'Candidatus Kotejella greeniscae' for its tentative classification. Both symbionts are transovarially transmitted from one generation to the next. The infection takes place in the neck region of the ovariole. The bacteria migrate between follicular cells, as well as through the cytoplasm of those cells to the perivitelline space, where they form a characteristic 'symbiont ball'. Our findings provide evidence for a polyphyletic origin of symbionts of Eriococcidae.}, } @article {pmid29393558, year = {2018}, author = {Turina, M and Ghignone, S and Astolfi, N and Silvestri, A and Bonfante, P and Lanfranco, L}, title = {The virome of the arbuscular mycorrhizal fungus Gigaspora margarita reveals the first report of DNA fragments corresponding to replicating non-retroviral RNA viruses in fungi.}, journal = {Environmental microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1111/1462-2920.14060}, pmid = {29393558}, issn = {1462-2920}, abstract = {Arbuscular Mycorrhizal Fungi (AMF) are key components of the plant microbiota. AMF genetic complexity is increased by the presence of endobacteria, which live inside many species. A further component of such complexity is the virome associated to AMF, whose knowledge is still very limited. Here, by exploiting transcriptomic data we describe the virome of Gigaspora margarita. A BLAST search for viral RNA-dependent RNA polymerases sequences allowed the identification of four mitoviruses, one Ourmia-like narnavirus, one Giardia-like virus, and two sequences related to Fusarium graminearum mycoviruses. Northern blot and RT-PCR confirmed the authenticity of all the sequences with the exception of the F. graminearum-related ones. All the mitoviruses are replicative and functional since both positive strand and negative strand RNA are present. The abundance of the viral RNA molecules is not regulated by the presence or absence of Candidatus Glomeribacter gigasporarum, the endobacterium hosted by G. margarita, with the exception of the Ourmia-like sequence which is absent in bacteria-cured spores. In addition, we report, for the first time, DNA fragments corresponding to mitovirus sequences associated to the presence of viral RNA. These sequences are not integrated in the mitochondrial DNA and preliminary evidence seems to exclude integration in the nuclear genome.}, } @article {pmid29393553, year = {2018}, author = {Bell, E and Blake, LI and Sherry, A and Head, IM and Hubert, CRJ}, title = {Distribution of thermophilic endospores in a temperate estuary indicate that dispersal history structures sediment microbial communities.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1134-1147}, doi = {10.1111/1462-2920.14056}, pmid = {29393553}, issn = {1462-2920}, abstract = {Endospores of thermophilic bacteria are found in cold and temperate sediments where they persist in a dormant state. As inactive endospores that cannot grow at the low ambient temperatures, they are akin to tracer particles in cold sediments, unaffected by factors normally governing microbial biogeography (e.g., selection, drift, mutation). This makes thermophilic endospores ideal model organisms for studying microbial biogeography since their spatial distribution can be directly related to their dispersal history. To assess dispersal histories of estuarine bacteria, thermophilic endospores were enriched from sediments along a freshwater-to-marine transect of the River Tyne in high temperature incubations (50°C). Dispersal histories for 75 different taxa indicated that the majority of estuarine endospores were of terrestrial origin; most closely related to bacteria from warm habitats associated with industrial activity. A subset of the taxa detected were marine derived, with close relatives from hot deep marine biosphere habitats. These patterns are consistent with the sources of sediment in the River Tyne being predominantly terrestrial in origin. The results point to microbial communities in estuarine and marine sediments being structured by bi-directional currents, terrestrial run-off and industrial effluent as vectors of passive dispersal and immigration.}, } @article {pmid29393123, year = {2018}, author = {Hoops, D}, title = {The Secret Caverns of the Dragon's Brain: Current and Potential Contributions of Lizards to Evolutionary Neuroscience.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {1}, pages = {1-3}, doi = {10.1159/000486529}, pmid = {29393123}, issn = {1421-9743}, } @article {pmid29392719, year = {2018}, author = {Samuk, K and Xue, J and Rennision, DJ}, title = {Exposure to predators does not lead to the evolution of larger brains in experimental populations of threespine stickleback.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {916-929}, doi = {10.1111/evo.13444}, pmid = {29392719}, issn = {1558-5646}, abstract = {Natural selection is often invoked to explain differences in brain size among vertebrates. However, the particular agents of selection that shape brain size variation remain obscure. Recent studies suggest that predators may select for larger brains because increased cognitive and sensory abilities allow prey to better elude predators. Yet, there is little direct evidence that exposure to predators causes the evolution of larger brains in prey species. We experimentally tested this prediction by exposing families of 1000-2000 F2 hybrid benthic-limnetic threespine stickleback to predators under naturalistic conditions, along with matched controls. After two generations of selection, we found that fish from the predator addition treatment had significantly smaller brains (specifically smaller telencephalons and optic lobes) than fish from the control treatment. After an additional generation of selection, we reared experimental fish in a common environment and found that this difference in brain size was maintained in the offspring of fish from the predator addition treatment. Our results provide direct experimental evidence that (a) predators can indeed drive the evolution of brain size--but not in the fashion commonly expected and (b) that the tools of experimental evolution can be used to the study the evolution of the vertebrate brain.}, } @article {pmid29392714, year = {2018}, author = {Cardinal, S and Buchmann, SL and Russell, AL}, title = {The evolution of floral sonication, a pollen foraging behavior used by bees (Anthophila).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {590-600}, pmid = {29392714}, issn = {1558-5646}, abstract = {Over 22,000 species of biotically pollinated flowering plants, including some major agricultural crops, depend primarily on bees capable of floral sonication for pollination services. The ability to sonicate ("buzz") flowers is widespread in bees but not ubiquitous. Despite the prevalence of this pollinator behavior and its importance to natural and agricultural systems, the evolutionary history of floral sonication in bees has not been previously studied. Here, we reconstruct the evolutionary history of floral sonication in bees by generating a time-calibrated phylogeny and reconstructing ancestral states for this pollen extraction behavior. We also test the hypothesis that the ability to sonicate flowers and thereby efficiently access pollen from a diverse assemblage of plant species, led to increased diversification among sonicating bee taxa. We find that floral sonication evolved on average 45 times within bees, possibly first during the Early Cretaceous (100-145 million years ago) in the common ancestor of bees. We find that sonicating lineages are significantly more species rich than nonsonicating sister lineages when comparing sister clades, but a probabilistic structured rate permutation on phylogenies approach failed to support the hypothesis that floral sonication is a key driver of bee diversification. This study provides the evolutionary framework needed to further study how floral sonication by bees may have facilitated the spread and common evolution of angiosperm species with poricidal floral morphology.}, } @article {pmid29392709, year = {2018}, author = {Duffield, KR and Hampton, KJ and Houslay, TM and Hunt, J and Rapkin, J and Sakaluk, SK and Sadd, BM}, title = {Age-dependent variation in the terminal investment threshold in male crickets.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {578-589}, doi = {10.1111/evo.13443}, pmid = {29392709}, issn = {1558-5646}, abstract = {The terminal investment hypothesis proposes that decreased expectation of future reproduction (e.g., arising from a threat to survival) should precipitate increased investment in current reproduction. The level at which a cue of decreased survival is sufficient to trigger terminal investment (i.e., the terminal investment threshold) may vary according to other factors that influence expectation for future reproduction. We test whether the terminal investment threshold varies with age in male crickets, using heat-killed bacteria to simulate an immune-inducing infection. We measured calling effort (a behavior essential for mating) and hemolymph antimicrobial activity in young and old males across a gradient of increasing infection cue intensity. There was a significant interaction between the infection cue and age in their effect on calling effort, confirming the existence of a dynamic terminal investment threshold: young males reduced effort at all infection levels, whereas old males increased effort at the highest levels relative to naïve individuals. A lack of a corresponding decrease in antibacterial activity suggests that altered reproductive effort is not traded against investment in this component of immunity. Collectively, these results support the existence of a dynamic terminal investment threshold, perhaps accounting for some of the conflicting evidence in support of terminal investment.}, } @article {pmid29392543, year = {2018}, author = {Villafañe-Barajas, SA and Baú, JPT and Colín-García, M and Negrón-Mendoza, A and Heredia-Barbero, A and Pi-Puig, T and Zaia, DAM}, title = {Salinity Effects on the Adsorption of Nucleic Acid Compounds on Na-Montmorillonite: a Prebiotic Chemistry Experiment.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {2}, pages = {181-200}, pmid = {29392543}, issn = {1573-0875}, support = {DGAPA-PAPIIT//DGAPA-PAPIIT/ ; protocol 24732//CNPq-Fundação Araucaria/ ; }, mesh = {Adenine/*chemistry ; Adenosine/*chemistry ; Adenosine Monophosphate/*chemistry ; Adsorption ; Bentonite/*chemistry ; Origin of Life ; *Salinity ; Sodium/*chemistry ; }, abstract = {Any proposed model of Earth's primitive environments requires a combination of geochemical variables. Many experiments are prepared in aqueous solutions and in the presence of minerals. However, most sorption experiments are performed in distilled water, and just a few in seawater analogues, mostly inconsistent with a representative primitive ocean model. Therefore, it is necessary to perform experiments that consider the composition and concentration of dissolved salts in the early ocean to understand how these variables could have affected the absorption of organic molecules into minerals. In this work, the adsorption of adenine, adenosine, and 5'AMP onto Na+montmorillonite was studied using a primitive ocean analog (4.0 Ga) from experimental and computational approaches. The order of sorption of the molecules was: 5'AMP > adenine > adenosine. Infrared spectra showed that the interaction between these molecules and montmorillonite occurs through the NH2 group. In addition, electrostatic interaction between negatively charged montmorillonite and positively charge N1 of these molecules could occur. Results indicate that dissolved salts affect the sorption in all cases; the size and structure of each organic molecule influence the amount sorbed. Specifically, the X-ray diffraction patterns show that dissolved salts occupy the interlayer space in Na-montmorillonite and compete with organic molecules for available sites. The adsorption capacity is clearly affected by dissolved salts in thermodynamic terms as deduced by isotherm models. Indeed, molecular dynamic models suggest that salts are absorbed in the interlamellar space and can interact with oxygen atoms exposed in the edges of clay or in its surface, reducing the sorption of the organic molecules. This research shows that the sorption process could be affected by high concentration of salts, since ions and organic molecules may compete for available sites on inorganic surfaces. Salt concentration in primitive oceans may have strongly affected the sorption, and hence the concentration processes of organic molecules on minerals.}, } @article {pmid29392473, year = {2018}, author = {Platt, RN and Vandewege, MW and Ray, DA}, title = {Mammalian transposable elements and their impacts on genome evolution.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {1-2}, pages = {25-43}, pmid = {29392473}, issn = {1573-6849}, mesh = {Animals ; DNA Transposable Elements/*genetics ; *Evolution, Molecular ; Genome/*genetics ; Humans ; Mammals/*genetics ; Retroelements ; }, abstract = {Transposable elements (TEs) are genetic elements with the ability to mobilize and replicate themselves in a genome. Mammalian genomes are dominated by TEs, which can reach copy numbers in the hundreds of thousands. As a result, TEs have had significant impacts on mammalian evolution. Here we summarize the current understanding of TE content in mammal genomes and find that, with a few exceptions, most fall within a predictable range of observations. First, one third to one half of the genome is derived from TEs. Second, most mammalian genomes are dominated by LINE and SINE retrotransposons, more limited LTR retrotransposons, and minimal DNA transposon accumulation. Third, most mammal genome contains at least one family of actively accumulating retrotransposon. Finally, horizontal transfer of TEs among lineages is rare. TE exaptation events are being recognized with increasing frequency. Despite these beneficial aspects of TE content and activity, the majority of TE insertions are neutral or deleterious. To limit the deleterious effects of TE proliferation, the genome has evolved several defense mechanisms that act at the epigenetic, transcriptional, and post-transcriptional levels. The interaction between TEs and these defense mechanisms has led to an evolutionary arms race where TEs are suppressed, evolve to escape suppression, then are suppressed again as the defense mechanisms undergo compensatory change. The result is complex and constantly evolving interactions between TEs and host genomes.}, } @article {pmid29391166, year = {2018}, author = {Tšuiko, O and Jatsenko, T and Parameswaran Grace, LK and Kurg, A and Vermeesch, JR and Lanner, F and Altmäe, S and Salumets, A}, title = {A speculative outlook on embryonic aneuploidy: Can molecular pathways be involved?.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.01.014}, pmid = {29391166}, issn = {1095-564X}, abstract = {The journey of embryonic development starts at oocyte fertilization, which triggers a complex cascade of events and cellular pathways that guide early embryogenesis. Recent technological advances have greatly expanded our knowledge of cleavage-stage embryo development, which is characterized by an increased rate of whole-chromosome losses and gains, mixoploidy, and atypical cleavage morphokinetics. Embryonic aneuploidy significantly contributes to implantation failure, spontaneous miscarriage, stillbirth or congenital birth defects in both natural and assisted human reproduction. Essentially, early embryo development is strongly determined by maternal factors. Owing to considerable limitations associated with human oocyte and embryo research, the use of animal models is inevitable. However, cellular and molecular mechanisms driving the error-prone early stages of development are still poorly described. In this review, we describe known events that lead to aneuploidy in mammalian oocytes and preimplantation embryos. As the processes of oocyte and embryo development are rigorously regulated by multiple signal-transduction pathways, we explore the putative role of signaling pathways in genomic integrity maintenance. Based on the existing evidence from human and animal data, we investigate whether critical early developmental pathways, like Wnt, Hippo and MAPK, together with distinct DNA damage response and DNA repair pathways can be associated with embryo genomic instability, a question that has, so far, remained largely unexplored.}, } @article {pmid29391165, year = {2018}, author = {Zhang, D and Osborne, JM and Abu-Bonsrah, KD and Cheeseman, BL and Landman, KA and Jurkowicz, B and Newgreen, DF}, title = {Stochastic clonal expansion of "superstars" enhances the reserve capacity of enteric nervous system precursor cells.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.01.020}, pmid = {29391165}, issn = {1095-564X}, abstract = {We quantified cell population increase in the quail embryo enteric nervous system (ENS) from E2.5 (about 1500 cells) to E12 (about 8 million cells). We then probed ENS proliferative capacity by grafting to the chorio-allantoic membrane large (600 cells) and small (40 cells) populations of enteric neural crest (ENC) cells with aneural gut. This demonstrated that ENC cells show an extremely high capacity to regulate their proliferation while forming the ENS. Previous mathematical models and clonal label experiments revealed that a few dominant ENS "superstar" cell clones emerge but most clones are small. The model implied that "superstars" arise stochastically, but the same outcome could arise if "superstars" were pre-determined. We investigated these two modes mathematically and by grafting experiments with large and small numbers of ENCs, each including one EGFP-labelled ENC cell. The stochastic model predicts that the frequency of "superstar" detection increases as the ENC population decreases, the pre-determined model does not. Experimentally, as predicted by the stochastic model, the frequency of "superstar" detection increased with small ENC cell number. We conclude that ENS "superstar" clones achieve this status stochastically. Clonal dominance implies that clonal diversity is greatly reduced and in this case, somatic mutations may affect the phenotype. We suggest that somatic mutations coupled with loss of clonal diversity may contribute to variable penetrance and expressivity in individuals with genetically identical ENS pathologies.}, } @article {pmid29391164, year = {2018}, author = {Han, AY and Gupta, S and Novitch, BG}, title = {Molecular specification of facial branchial motor neurons in vertebrates.}, journal = {Developmental biology}, volume = {436}, number = {1}, pages = {5-13}, doi = {10.1016/j.ydbio.2018.01.019}, pmid = {29391164}, issn = {1095-564X}, mesh = {Animals ; Body Patterning/genetics ; Cell Movement/genetics ; Facial Nerve/embryology/*metabolism ; Motor Neurons/*metabolism ; Neurogenesis/*genetics ; Vertebrates/embryology/metabolism ; }, abstract = {Orofacial muscles are critical for life-sustaining behaviors, such as feeding and breathing. Centuries of work by neuroanatomists and surgeons resulted in the mapping of bulbar motor neurons in the brainstem and the course of the cranial nerves that carry their axons. Despite the sophisticated understanding of the anatomy of the region, the molecular mechanisms that dictate the development and maturation of facial motor neurons remain poorly understood. This fundamental problem has been recently revisited by physiologists with novel techniques of studying the rhythmic contraction of orofacial muscles in relationship to breathing. The molecular understanding of facial motor neuron development will not only lead to the comprehension of the neural basis of facial expression but may also unlock new avenues to generate stem cell-derived replacements. This review summarizes the current understanding of molecular programs involved in facial motor neuron generation, migration, and maturation, including neural circuit assembly.}, } @article {pmid29391060, year = {2018}, author = {Hu, J and Jiang, J}, title = {Inferring ecological explanations for biogeographic boundaries of parapatric Asian mountain frogs.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {3}, pmid = {29391060}, issn = {1472-6785}, support = {31572290//National Natural Science Foundation of China/International ; 31270568//National Natural Science Foundation of China/International ; 2015304//Youth Innovation Promotion Association of the Chinese Academy of Sciences/International ; 2014JQ0056//Sichuan Province Distinguished Youth Fund/International ; 2016YFC0503303//National Key Research and Development Plan/International ; }, abstract = {BACKGROUND: Identifying and understanding the mechanisms that shape barriers to dispersal and resulting biogeographic boundaries has been a longstanding, yet challenging, goal in ecology, evolution and biogeography. Characterized by stable, adjacent ranges, without any intervening physical barriers, and limited, if any, range overlap in a narrow contact zone, parapatric species are an interesting system for studying biogeographic boundaries. The geographic ranges of two parapatric frog species, Feirana quadranus and F. taihangnica, meet in a contact zone within the Qinling Mountains, an important watershed for East Asia. To identify possible ecological determinants of the parapatric range boundaries for two closely related frog species, we quantified the extent of their niche differentiation in both geographical and environmental space combining ecological niche models with an ordination technique. We tested two alternative null hypotheses (sharp environmental gradients versus a ribbon of unsuitable habitat dividing two highly suitable regions) for biogeographic boundaries, against the null expectation that environmental variation across a given boundary is no greater than expected by chance.

RESULTS: We found that the niches of these two parapatric species are more similar than expected by chance, but not equivalent. No sharp environmental gradient was found, while a ribbon of unsuitable habitat did act as a barrier for F. quadranus, but not for F. taihangnica.

CONCLUSIONS: Integrating our findings with historical biogeographic information, our results suggest that at a contact zone, environmental tolerance restricted F. quadranus from dispersing further north, while interspecific competition most likely prevented the southward expansion of F. taihangnica. This study highlights the importance of both climate and competition in exploring ecological explanations for parapatric range boundaries between ecologically similar frog species, in particular under the effects of changing climate.}, } @article {pmid29391058, year = {2018}, author = {Franklin, AB and Carlson, PC and Rex, A and Rockweit, JT and Garza, D and Culhane, E and Volker, SF and Dusek, RJ and Shearn-Bochsler, VI and Gabriel, MW and Horak, KE}, title = {Grass is not always greener: rodenticide exposure of a threatened species near marijuana growing operations.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {94}, pmid = {29391058}, issn = {1756-0500}, mesh = {4-Hydroxycoumarins/*poisoning ; Animals ; Anticoagulants/*poisoning ; California ; Cannabis/*growth & development/parasitology ; Endangered Species ; Fatal Outcome ; Female ; Plant Breeding ; Rodentia/metabolism ; Rodenticides/*poisoning ; *Strigiformes ; }, abstract = {OBJECTIVE: Marijuana (Cannabis spp.) growing operations (MGO) in California have increased substantially since the mid-1990s. One environmental side-effect of MGOs is the extensive use of anticoagulant rodenticides (AR) to prevent damage to marijuana plants caused by wild rodents. In association with a long-term demographic study, we report on an observation of brodifacoum AR exposure in a threatened species, the northern spotted owl (Strix occidentalis caurina), found freshly dead within 669-1347 m of at least seven active MGOs.

RESULTS: Liver and blood samples from the dead northern spotted owl were tested for 12 rodenticides. Brodifacoum was the only rodenticide detected in the liver (33.3-36.3 ng/g) and blood (0.48-0.54 ng/ml). Based on necropsy results, it was unclear what role brodifacoum had in the death of this bird. However, fatal AR poisoning has been previously reported in owls with relatively low levels of brodifacoum residues in the liver. One likely mechanism of AR transmission from MGOs to northern spotted owls in California is through ingestion of AR contaminated prey that frequent MGOs. The proliferation of MGOs with their use of ARs in forested landscapes used by northern spotted owls may pose an additional stressor for this threatened species.}, } @article {pmid29391057, year = {2018}, author = {Ma, Y and You, X and Mai, G and Tokuyasu, T and Liu, C}, title = {A human gut phage catalog correlates the gut phageome with type 2 diabetes.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {24}, pmid = {29391057}, issn = {2049-2618}, support = {31570115//NSFC/International ; JSGG20160229145252927//Science and Technology Key Projects of Shenzhen/International ; JCYJ20160229201759414//Science and Technology Key Projects of Shenzhen/International ; JCYJ20160122143446357//Science and Technology Key Projects of Shenzhen/International ; S2013050016987//The Guangdong Natural Science Funds for Distinguished Young Scholar Grant/International ; KQTD2015033117210153//The Shenzhen Peacock Team Project/International ; KQCX2015033117354154//The Shenzhen Peacock Project/International ; }, mesh = {Bacteria/*virology ; Bacteriophages/*classification/genetics/isolation & purification ; Case-Control Studies ; China ; Computational Biology ; Diabetes Mellitus, Type 2/*microbiology ; Feces/microbiology ; Gastrointestinal Tract/*microbiology ; Humans ; Phylogeny ; }, abstract = {BACKGROUND: Substantial efforts have been made to link the gut bacterial community to many complex human diseases. Nevertheless, the gut phages are often neglected.

RESULTS: In this study, we used multiple bioinformatic methods to catalog gut phages from whole-community metagenomic sequencing data of fecal samples collected from both type II diabetes (T2D) patients (n = 71) and normal Chinese adults (n = 74). The definition of phage operational taxonomic units (pOTUs) and identification of large phage scaffolds (n = 2567, ≥ 10 k) revealed a comprehensive human gut phageome with a substantial number of novel sequences encoding genes that were unrelated to those in known phages. Interestingly, we observed a significant increase in the number of gut phages in the T2D group and, in particular, identified 7 pOTUs specific to T2D. This finding was further validated in an independent dataset of 116 T2D and 109 control samples. Co-occurrence/exclusion analysis of the bacterial genera and pOTUs identified a complex core interaction between bacteria and phages in the human gut ecosystem, suggesting that the significant alterations of the gut phageome cannot be explained simply by co-variation with the altered bacterial hosts.

CONCLUSIONS: Alterations in the gut bacterial community have been linked to the chronic disease T2D, but the role of gut phages therein is not well understood. This is the first study to identify a T2D-specific gut phageome, indicating the existence of other mechanisms that might govern the gut phageome in T2D patients. These findings suggest the importance of the phageome in T2D risk, which warrants further investigation.}, } @article {pmid29391052, year = {2018}, author = {Velders, AH and Schoen, C and Saggiomo, V}, title = {Loop-mediated isothermal amplification (LAMP) shield for Arduino DNA detection.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {93}, pmid = {29391052}, issn = {1756-0500}, mesh = {Base Sequence ; DNA Primers/*chemistry ; DNA, Bacterial/*genetics ; *Mobile Applications ; Nucleic Acid Amplification Techniques/*instrumentation ; Pseudomonas syringae/genetics ; Sensitivity and Specificity ; }, abstract = {OBJECTIVE: Loop-mediated isothermal amplification (LAMP) of DNA is gaining relevance as a method to detect nucleic acids, as it is easier, faster, and more powerful than conventional Polymerase Chain Reaction. However, LAMP is still mostly used in laboratory settings, because of the lack of a cheap and easy, one-button device that can perform LAMP experiments.

RESULTS: Here we show how to build and program an Arduino shield for a LAMP and detection of DNA. The here described Arduino Shield is cheap, easy to assemble, to program and use, it is battery operated and the detection of DNA is done by naked-eye so that it can be used in field.}, } @article {pmid29391046, year = {2018}, author = {Avoka, JA and Adanu, RM and Wombeogo, M and Seidu, I and Dun-Dery, EJ}, title = {Maternal and neonatal characteristics that influence very early neonatal mortality in the Eastern Regional Hospital of Ghana, Koforidua: a retrospective review.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {91}, pmid = {29391046}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Female ; Ghana/epidemiology ; Hospitals ; Humans ; Infant ; Infant Mortality/*trends ; Infant, Newborn ; Maternal Age ; Parity/*physiology ; *Perinatal Death ; Pregnancy ; Retrospective Studies ; Risk Factors ; }, abstract = {OBJECTIVE: This study was conducted to determine the maternal and neonatal characteristics that influence very early neonatal mortality using 811 delivery records at the Eastern Regional Hospital of Ghana.

RESULTS: The very early neonatal mortality rate was 9 per 1000 live births. Multi-parity reduced the odds of very early neonatal death by 30%. Mothers with a previous neonatal death had about 8 times the odds of having a very early neonatal death as compared to those without a history of neonatal death.}, } @article {pmid29391045, year = {2018}, author = {Guillemin, A and Richard, A and Gonin-Giraud, S and Gandrillon, O}, title = {Automated cell cycle and cell size measurements for single-cell gene expression studies.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {92}, pmid = {29391045}, issn = {1756-0500}, support = {ANR-IABI-3096//ICEBERG/ ; }, mesh = {Animals ; Automation, Laboratory ; Avian Proteins/*genetics/metabolism ; Cation Transport Proteins/genetics/metabolism ; Cell Cycle/*genetics ; Cell Proliferation ; Cell Size ; Chickens ; Erythroid Precursor Cells/cytology/*metabolism ; Gene Expression Profiling ; Genetic Variation ; HSP90 Heat-Shock Proteins/genetics/metabolism ; Primary Cell Culture ; Single-Cell Analysis/*methods ; Staining and Labeling/methods ; *Transcriptome ; beta-Globins/genetics/metabolism ; }, abstract = {OBJECTIVES: Recent rise of single-cell studies revealed the importance of understanding the role of cell-to-cell variability, especially at the transcriptomic level. One of the numerous sources of cell-to-cell variation in gene expression is the heterogeneity in cell proliferation state. In order to identify how cell cycle and cell size influences gene expression variability at the single-cell level, we provide an universal and automatic toxic-free label method, compatible with single-cell high-throughput RT-qPCR. The method consists of isolating cells after a double-stained, analyzing their morphological parameters and performing a transcriptomic analysis on the same identified cells.

RESULTS: This led to an unbiased gene expression analysis and could be also used for improving single-cell tracking and imaging when combined with cell isolation. As an application for this technique, we showed that cell-to-cell variability in chicken erythroid progenitors was negligibly influenced by cell size nor cell cycle.}, } @article {pmid29391044, year = {2018}, author = {Arango-Argoty, G and Garner, E and Pruden, A and Heath, LS and Vikesland, P and Zhang, L}, title = {DeepARG: a deep learning approach for predicting antibiotic resistance genes from metagenomic data.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {23}, pmid = {29391044}, issn = {2049-2618}, support = {2015-68003-23050//U.S. Department of Agriculture/International ; 1545756//National Science Foundation/International ; }, mesh = {Computational Biology/*methods ; *Drug Resistance, Microbial ; Gene Regulatory Networks ; High-Throughput Nucleotide Sequencing ; Humans ; Machine Learning ; *Metagenome ; Software ; }, abstract = {BACKGROUND: Growing concerns about increasing rates of antibiotic resistance call for expanded and comprehensive global monitoring. Advancing methods for monitoring of environmental media (e.g., wastewater, agricultural waste, food, and water) is especially needed for identifying potential resources of novel antibiotic resistance genes (ARGs), hot spots for gene exchange, and as pathways for the spread of ARGs and human exposure. Next-generation sequencing now enables direct access and profiling of the total metagenomic DNA pool, where ARGs are typically identified or predicted based on the "best hits" of sequence searches against existing databases. Unfortunately, this approach produces a high rate of false negatives. To address such limitations, we propose here a deep learning approach, taking into account a dissimilarity matrix created using all known categories of ARGs. Two deep learning models, DeepARG-SS and DeepARG-LS, were constructed for short read sequences and full gene length sequences, respectively.

RESULTS: Evaluation of the deep learning models over 30 antibiotic resistance categories demonstrates that the DeepARG models can predict ARGs with both high precision (> 0.97) and recall (> 0.90). The models displayed an advantage over the typical best hit approach, yielding consistently lower false negative rates and thus higher overall recall (> 0.9). As more data become available for under-represented ARG categories, the DeepARG models' performance can be expected to be further enhanced due to the nature of the underlying neural networks. Our newly developed ARG database, DeepARG-DB, encompasses ARGs predicted with a high degree of confidence and extensive manual inspection, greatly expanding current ARG repositories.

CONCLUSIONS: The deep learning models developed here offer more accurate antimicrobial resistance annotation relative to current bioinformatics practice. DeepARG does not require strict cutoffs, which enables identification of a much broader diversity of ARGs. The DeepARG models and database are available as a command line version and as a Web service at http://bench.cs.vt.edu/deeparg .}, } @article {pmid29391039, year = {2018}, author = {Rankgoane-Pono, G and Tshikuka, JG and Magafu, MGMD and Masupe, T and Molefi, M and Hamda, SG and Setlhare, V and Tapera, R and Mbongwe, B}, title = {Incidence of diabetes mellitus-related comorbidities among patients attending two major HIV clinics in Botswana: a 12-year retrospective cohort study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {90}, pmid = {29391039}, issn = {1756-0500}, support = {T84HA22125//U.S. Department of Health and Human Services (HHS)/ ; }, mesh = {Adult ; Anti-HIV Agents/*therapeutic use ; Antiretroviral Therapy, Highly Active/methods ; Botswana/epidemiology ; CD4 Lymphocyte Count ; Comorbidity ; Diabetes Mellitus, Type 2/*drug therapy/*epidemiology/immunology/virology ; Female ; HIV Infections/*drug therapy/*epidemiology/immunology/virology ; HIV-1/drug effects/growth & development ; Humans ; Incidence ; Male ; Middle Aged ; Retrospective Studies ; Viral Load/drug effects ; }, abstract = {OBJECTIVES: Exposure to combination antiretroviral therapy (cART) is associated with the development of diabetes mellitus related comorbidities (DRCs). This study aims to: (i) estimate the incidence of DRCs among cART recipients, (ii) assess the time-to-event (development of DRC) and, (iii) compare survival function between recipients on first-line regimen and those on second-, third-line cART regimen.

RESULTS: The incidence of DRCs was 26.8/1000 person-years, with total time of exposure of 3316 person-years. The average time to event for all the three regimens was 11.72 ± 0.20 years. The first-line cART regimen had a shorter mean ± SE of 10.59 ± 0.26 years to the event compared to 12.69 ± 0.24 years for the second-, third-line cART regimen. Recipients on the first-line had a shorter survival than recipients on second-, third-line cART (Log-rank X2 = 8.98, p < 0.003). Data from this study showed that the risk of developing DRCs per year of exposure was significantly greater for patients on first-line compared to those who were on second-, third-line regimen; which, suggests that monitoring of cART long-term side effects and regular reviewing of cART regimens is important. Meticulous selection of drug combinations is a key to improving recipients' survival.}, } @article {pmid29391007, year = {2018}, author = {Pearce, SC and Al-Jawadi, A and Kishida, K and Yu, S and Hu, M and Fritzky, LF and Edelblum, KL and Gao, N and Ferraris, RP}, title = {Marked differences in tight junction composition and macromolecular permeability among different intestinal cell types.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {19}, pmid = {29391007}, issn = {1741-7007}, support = {R01 DK102934/DK/NIDDK NIH HHS/United States ; }, abstract = {BACKGROUND: Mammalian small intestinal tight junctions (TJ) link epithelial cells to one another and function as a permselective barrier, strictly modulating the passage of ions and macromolecules through the pore and leak pathways, respectively, thereby preventing the absorption of harmful compounds and microbes while allowing regulated transport of nutrients and electrolytes. Small intestinal epithelial permeability is ascribed primarily to the properties of TJs between adjoining enterocytes (ENTs), because there is almost no information on TJ composition and the paracellular permeability of nonenterocyte cell types that constitute a small but significant fraction of the intestinal epithelia.

RESULTS: Here we directed murine intestinal crypts to form specialized organoids highly enriched in intestinal stem cells (ISCs), absorptive ENTs, secretory goblet cells, or Paneth cells. The morphological and morphometric characteristics of these cells in organoids were similar to those in vivo. The expression of certain TJ proteins varied with cell type: occludin and tricellulin levels were high in both ISCs and Paneth cells, while claudin-1, -2, and -7 expression was greatest in Paneth cells, ISCs, and ENTs, respectively. In contrast, the distribution of claudin-15, zonula occludens 1 (ZO-1), and E-cadherin was relatively homogeneous. E-cadherin and claudin-7 marked mainly the basolateral membrane, while claudin-2, ZO-1, and occludin resided in the apical membrane. Remarkably, organoids enriched in ENTs or goblet cells were over threefold more permeable to 4 and 10 kDa dextran compared to those containing stem and Paneth cells. The TJ-regulator larazotide prevented the approximately tenfold increases in dextran flux induced by the TJ-disrupter AT1002 into organoids of different cell types, indicating that this ZO toxin nonselectively increases permeability. Forced dedifferentiation of mature ENTs results in the reacquisition of ISC-like characteristics in TJ composition and dextran permeability, suggesting that the post-differentiation properties of TJs are not hardwired.

CONCLUSIONS: Differentiation of adult intestinal stem cells into mature secretory and absorptive cell types causes marked, but potentially reversible, changes in TJ composition, resulting in enhanced macromolecular permeability of the TJ leak pathway between ENTs and between goblet cells. This work advances our understanding of how cell differentiation affects the paracellular pathway of epithelia.}, } @article {pmid29390973, year = {2018}, author = {Hoang, DT and Vinh, LS and Flouri, T and Stamatakis, A and von Haeseler, A and Minh, BQ}, title = {MPBoot: fast phylogenetic maximum parsimony tree inference and bootstrap approximation.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {11}, pmid = {29390973}, issn = {1471-2148}, support = {I-2805-B29//Austrian Science Fund (AT)/International ; STA860-6/1//Deutsche Forschungsgemeinschaft/International ; 102.01-2013.04//National Foundation for Science and Technology Development/International ; }, mesh = {DNA/genetics ; Likelihood Functions ; Models, Genetic ; *Phylogeny ; Sequence Alignment ; *Software ; Time Factors ; }, abstract = {BACKGROUND: The nonparametric bootstrap is widely used to measure the branch support of phylogenetic trees. However, bootstrapping is computationally expensive and remains a bottleneck in phylogenetic analyses. Recently, an ultrafast bootstrap approximation (UFBoot) approach was proposed for maximum likelihood analyses. However, such an approach is still missing for maximum parsimony.

RESULTS: To close this gap we present MPBoot, an adaptation and extension of UFBoot to compute branch supports under the maximum parsimony principle. MPBoot works for both uniform and non-uniform cost matrices. Our analyses on biological DNA and protein showed that under uniform cost matrices, MPBoot runs on average 4.7 (DNA) to 7 times (protein data) (range: 1.2-20.7) faster than the standard parsimony bootstrap implemented in PAUP*; but 1.6 (DNA) to 4.1 times (protein data) slower than the standard bootstrap with a fast search routine in TNT (fast-TNT). However, for non-uniform cost matrices MPBoot is 5 (DNA) to 13 times (protein data) (range:0.3-63.9) faster than fast-TNT. We note that MPBoot achieves better scores more frequently than PAUP* and fast-TNT. However, this effect is less pronounced if an intensive but slower search in TNT is invoked. Moreover, experiments on large-scale simulated data show that while both PAUP* and TNT bootstrap estimates are too conservative, MPBoot bootstrap estimates appear more unbiased.

CONCLUSIONS: MPBoot provides an efficient alternative to the standard maximum parsimony bootstrap procedure. It shows favorable performance in terms of run time, the capability of finding a maximum parsimony tree, and high bootstrap accuracy on simulated as well as empirical data sets. MPBoot is easy-to-use, open-source and available at http://www.cibiv.at/software/mpboot .}, } @article {pmid29390967, year = {2018}, author = {Xin, J and Afrasiabi, C and Lelong, S and Adesara, J and Tsueng, G and Su, AI and Wu, C}, title = {Cross-linking BioThings APIs through JSON-LD to facilitate knowledge exploration.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {30}, pmid = {29390967}, issn = {1471-2105}, support = {U01 HG008473/HG/NHGRI NIH HHS/United States ; U01HG008473/HG/NHGRI NIH HHS/United States ; }, mesh = {Biological Science Disciplines ; Databases, Factual ; Humans ; Information Storage and Retrieval/*methods ; Internet ; *Software ; }, abstract = {BACKGROUND: Application Programming Interfaces (APIs) are now widely used to distribute biological data. And many popular biological APIs developed by many different research teams have adopted Javascript Object Notation (JSON) as their primary data format. While usage of a common data format offers significant advantages, that alone is not sufficient for rich integrative queries across APIs.

RESULTS: Here, we have implemented JSON for Linking Data (JSON-LD) technology on the BioThings APIs that we have developed, MyGene.info , MyVariant.info and MyChem.info . JSON-LD provides a standard way to add semantic context to the existing JSON data structure, for the purpose of enhancing the interoperability between APIs. We demonstrated several use cases that were facilitated by semantic annotations using JSON-LD, including simpler and more precise query capabilities as well as API cross-linking.

CONCLUSIONS: We believe that this pattern offers a generalizable solution for interoperability of APIs in the life sciences.}, } @article {pmid29390965, year = {2018}, author = {Sadkowski, T and Ciecierska, A and Oprządek, J and Balcerek, E}, title = {Breed-dependent microRNA expression in the primary culture of skeletal muscle cells subjected to myogenic differentiation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {109}, pmid = {29390965}, issn = {1471-2164}, support = {2011/03/B/NZ9/03987//Narodowe Centrum Nauki/International ; }, mesh = {Animals ; *Breeding ; Cattle ; *Cell Differentiation ; Cells, Cultured ; *Gene Expression Regulation ; MicroRNAs/*genetics ; Microarray Analysis/methods ; Muscle Development ; Muscle, Skeletal/cytology/*metabolism ; Myoblasts/cytology/*metabolism ; }, abstract = {BACKGROUND: Skeletal muscle in livestock develops into meat, an important source of protein and other nutrients for human consumption. The muscle is largely composed of a fixed number of multinucleated myofibers determined during late gestation and remains constant postnatally. A population of postnatal muscle stem cells, called satellite cells, gives rise to myoblast cells that can fuse with the existing myofibers, thus increasing their size. This requires a delicate balance of transcription and growth factors and specific microRNA (miRNA) expressed by satellite cells and their supporting cells from the muscle stem cell niche. The role of transcription and growth factors in bovine myogenesis is well-characterized; however, very little is known about the miRNA activity during this process. We have hypothesized that the expression of miRNA can vary between primary cultures of skeletal muscle cells isolated from the semitendinosus muscles of different cattle breeds and subjected to myogenic differentiation.

RESULTS: After a 6-day myogenic differentiation of cells isolated from the muscles of the examined cattle breeds, we found statistically significant differences in the number of myotubes between Hereford (HER)/Limousine (LIM) beef breeds and the Holstein-Friesian (HF) dairy breed (p ≤ 0.001). The microarray analysis revealed differences in the expression of 23 miRNA among the aforementioned primary cultures. On the basis of a functional analysis, we assigned 9 miRNA as molecules responsible for differentiation progression (miR-1, -128a, -133a, -133b, -139, -206, -222, -486, and -503). The target gene prediction and functional analysis revealed 59 miRNA-related genes belonging to the muscle organ development process.

CONCLUSION: The number of myotubes and the miRNA expression in the primary cultures of skeletal muscle cells derived from the semitendinosus muscles of the HER/LIM beef cattle breeds and the HF dairy breed vary when cells are subjected to myogenic differentiation. The net effect of the identified miRNA and their target gene action should be considered the result of the breed-dependent activity of satellite cells and muscle stem cell niche cells and their mutual interactions, which putatively can be engaged in the formation of a larger number of myotubes in beef cattle-related cells (HER/LIM) during in vitro myogenesis.}, } @article {pmid29390964, year = {2018}, author = {Espinola, SM and Cancela, MP and Brisolara Corrêa, L and Zaha, A}, title = {Evolutionary fates of universal stress protein paralogs in Platyhelminthes.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {10}, pmid = {29390964}, issn = {1471-2148}, support = {1278/2011//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior/International ; 472316/2013-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; }, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Gene Duplication ; Gene Expression Regulation ; Genetic Variation ; Heat-Shock Proteins/chemistry/*genetics ; Models, Molecular ; Multigene Family ; Nucleotide Motifs/genetics ; Phylogeny ; Platyhelminths/*genetics ; Pseudogenes ; Selection, Genetic ; *Sequence Homology, Amino Acid ; }, abstract = {BACKGROUND: Universal stress proteins (USPs) are present in all domains of life. Their expression is upregulated in response to a large variety of stress conditions. The functional diversity found in this protein family, paired with the sequence degeneration of the characteristic ATP-binding motif, suggests a complex evolutionary pattern for the paralogous USP-encoding genes. In this work, we investigated the origin, genomic organization, expression patterns and evolutionary history of the USP gene family in species of the phylum Platyhelminthes.

RESULTS: Our data showed a cluster organization, a lineage-specific distribution, and the presence of several pseudogenes among the USP gene copies identified. The absence of a well conserved -CCAATCA- motif in the promoter region was positively correlated with low or null levels of gene expression, and with amino acid changes within the ligand binding motifs. Despite evidence of the pseudogenization of various USP genes, we detected an important functional divergence at several residues, mostly located near sites that are critical for ligand interaction.

CONCLUSIONS: Our results provide a broad framework for the evolution of the USP gene family, based on the emergence of new paralogs that face very contrasting fates, including pseudogenization, subfunctionalization or neofunctionalization. This framework aims to explain the sequence and functional diversity of this gene family, providing a foundation for future studies in other taxa in which USPs occur.}, } @article {pmid29390960, year = {2018}, author = {Kvikstad, EM and Piazza, P and Taylor, JC and Lunter, G}, title = {A high throughput screen for active human transposable elements.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {115}, pmid = {29390960}, issn = {1471-2164}, support = {090532/Z/09/Z//Wellcome Trust/United Kingdom ; }, mesh = {*Algorithms ; *DNA Transposable Elements ; Gene Library ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Transposable elements (TEs) are mobile genetic sequences that randomly propagate within their host's genome. This mobility has the potential to affect gene transcription and cause disease. However, TEs are technically challenging to identify, which complicates efforts to assess the impact of TE insertions on disease. Here we present a targeted sequencing protocol and computational pipeline to identify polymorphic and novel TE insertions using next-generation sequencing: TE-NGS. The method simultaneously targets the three subfamilies that are responsible for the majority of recent TE activity (L1HS, AluYa5/8, and AluYb8/9) thereby obviating the need for multiple experiments and reducing the amount of input material required.

RESULTS: Here we describe the laboratory protocol and detection algorithm, and a benchmark experiment for the reference genome NA12878. We demonstrate a substantial enrichment for on-target fragments, and high sensitivity and precision to both reference and NA12878-specific insertions. We report 17 previously unreported loci for this individual which are supported by orthogonal long-read evidence, and we identify 1470 polymorphic and novel TEs in 12 additional samples that were previously undocumented in databases of insertion polymorphisms.

CONCLUSIONS: We anticipate that future applications of TE-NGS alongside exome sequencing of patients with sporadic disease will reduce the number of unresolved cases, and improve estimates of the contribution of TEs to human genetic disease.}, } @article {pmid29390959, year = {2018}, author = {Bonzom, C and Schild, L and Gustafsson, H and Olsson, L}, title = {Feruloyl esterase immobilization in mesoporous silica particles and characterization in hydrolysis and transesterification.}, journal = {BMC biochemistry}, volume = {19}, number = {1}, pages = {1}, pmid = {29390959}, issn = {1471-2091}, support = {349-2007-8680//Vetenskapsrådet/International ; }, mesh = {Buffers ; Carboxylic Ester Hydrolases/*metabolism ; Enzyme Stability ; Enzymes, Immobilized/*standards ; Esterification ; Hydrogen-Ion Concentration ; Hydrolysis ; Porosity ; Silicon Dioxide/*chemistry ; }, abstract = {BACKGROUND: Enzymes display high reactivity and selectivity under natural conditions, but may suffer from decreased efficiency in industrial applications. A strategy to address this limitation is to immobilize the enzyme. Mesoporous silica materials offer unique properties as an immobilization support, such as high surface area and tunable pore size.

RESULTS: The performance of a commercially available feruloyl esterase, E-FAERU, immobilized on mesoporous silica by physical adsorption was evaluated for its transesterification ability. We optimized the immobilization conditions by varying the support pore size, the immobilization buffer and its pH. Maximum loading and maximum activity were achieved at different pHs (4.0 and 6.0 respectively). Selectivity, shown by the transesterification/hydrolysis products molar ratio, varied more than 3-fold depending on the reaction buffer used and its pH. Under all conditions studied, hydrolysis was the dominant activity of the enzyme. pH and water content had the greatest influence on the enzyme selectivity and activity. Determined kinetic parameters of the enzyme were obtained and showed that Km was not affected by the immobilization but kcat was reduced 10-fold when comparing the free and immobilized enzymes. Thermal and pH stabilities as well as the reusability were investigated. The immobilized biocatalyst retained more than 20% of its activity after ten cycles of transesterification reaction.

CONCLUSIONS: These results indicate that this enzyme is more suited for hydrolysis reactions than transesterification despite good reusability. Furthermore, it was found that the immobilization conditions are crucial for optimal enzyme activity as they can alter the enzyme performance.}, } @article {pmid29390958, year = {2018}, author = {Gao, J and Yang, Y and Zhou, Y}, title = {Grid-based prediction of torsion angle probabilities of protein backbone and its application to discrimination of protein intrinsic disorder regions and selection of model structures.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {29}, pmid = {29390958}, issn = {1471-2105}, support = {11701296//the National Natural Science Foundation of China/International ; U1611261,61772566//the National Natural Science Foundation of China/International ; 2016ZT06D211//the program for Guangdong Introducing Innovative and Entrepreneurial Teams/International ; 1059775,1083450//National Health and Medical Research Council of Australia/International ; LE150100161,DP180102060//Australian Research Council's Linkage Infra-structure, Equipment and Facilities funding scheme/International ; }, mesh = {Area Under Curve ; Neural Networks (Computer) ; Probability ; Protein Domains ; Protein Structure, Tertiary ; Proteins/*chemistry/metabolism ; ROC Curve ; *User-Computer Interface ; }, abstract = {BACKGROUND: Protein structure can be described by backbone torsion angles: rotational angles about the N-Cα bond (φ) and the Cα-C bond (ψ) or the angle between Cαi-1-Cαi-Cαi + 1 (θ) and the rotational angle about the Cαi-Cαi + 1 bond (τ). Thus, their accurate prediction is useful for structure prediction and model refinement. Early methods predicted torsion angles in a few discrete bins whereas most recent methods have focused on prediction of angles in real, continuous values. Real value prediction, however, is unable to provide the information on probabilities of predicted angles.

RESULTS: Here, we propose to predict angles in fine grids of 5° by using deep learning neural networks. We found that this grid-based technique can yield 2-6% higher accuracy in predicting angles in the same 5° bin than existing prediction techniques compared. We further demonstrate the usefulness of predicted probabilities at given angle bins in discrimination of intrinsically disorder regions and in selection of protein models.

CONCLUSIONS: The proposed method may be useful for characterizing protein structure and disorder. The method is available at http://sparks-lab.org/server/SPIDER2/ as a part of SPIDER2 package.}, } @article {pmid29390143, year = {2018}, author = {Han, D and Dedysh, SN and Liesack, W}, title = {Unusual Genomic Traits Suggest Methylocystis bryophila S285 to Be Well Adapted for Life in Peatlands.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {623-628}, pmid = {29390143}, issn = {1759-6653}, mesh = {Adaptation, Biological ; Bacterial Proteins/genetics/metabolism ; Carbon/metabolism ; *Genome, Bacterial ; Methylocystaceae/enzymology/*genetics/physiology ; Multigene Family ; Nitrogen Fixation ; Oxygenases/genetics/metabolism ; Wetlands ; }, abstract = {The genus Methylocystis belongs to the class Alphaproteobacteria, the family Methylocystaceae, and encompasses aerobic methanotrophic bacteria with the serine pathway of carbon assimilation. All Methylocystis species are able to fix dinitrogen and several members of this genus are also capable of using acetate or ethanol in the absence of methane, which explains their wide distribution in various habitats. One additional trait that enables their survival in the environment is possession of two methane-oxidizing isozymes, the conventional particulate methane monooxygenase (pMMO) with low-affinity to substrate (pMMO1) and the high-affinity enzyme (pMMO2). Here, we report the finished genome sequence of Methylocystis bryophila S285, a pMMO2-possessing methanotroph from a Sphagnum-dominated wetland, and compare it to the genome of Methylocystis sp. strain SC2, which is the first methanotroph with confirmed high-affinity methane oxidation potential. The complete genome of Methylocystis bryophila S285 consists of a 4.53 Mb chromosome and one plasmid, 175 kb in size. The genome encodes two types of particulate MMO (pMMO1 and pMMO2), soluble MMO and, in addition, contains a pxmABC-like gene cluster similar to that present in some gammaproteobacterial methanotrophs. The full set of genes related to the serine pathway, the tricarboxylic acid cycle as well as the ethylmalonyl-CoA pathway is present. In contrast to most described methanotrophs including Methylocystis sp. strain SC2, two different types of nitrogenases, that is, molybdenum-iron and vanadium-iron types, are encoded in the genome of strain S285. This unique combination of genome-based traits makes Methylocystis bryophila well adapted to the fluctuation of carbon and nitrogen sources in wetlands.}, } @article {pmid29390142, year = {2018}, author = {Zélé, F and Santos, I and Olivieri, I and Weill, M and Duron, O and Magalhães, S}, title = {Endosymbiont diversity and prevalence in herbivorous spider mite populations in South-Western Europe.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy015}, pmid = {29390142}, issn = {1574-6941}, abstract = {Bacterial endosymbionts are known as important players of the evolutionary ecology of their hosts. However, their distribution, prevalence and diversity are still largely unexplored. To this aim, we investigated infections by the most common bacterial reproductive manipulators in herbivorous spider mites of South-Western Europe. Across 16 populations belonging to three Tetranychus species, Wolbachia was the most prevalent (ca. 61%), followed by Cardinium (12%-15%), while only few individuals were infected by Rickettsia (0.9%-3%), and none carried Arsenophonus or Spiroplasma. These endosymbionts are here reported for the first time in Tetranychus evansi and Tetranychus ludeni, and showed variable infection frequencies between and within species, with several cases of coinfections. Moreover, Cardinium was more prevalent in Wolbachia-infected individuals, which suggests facilitation between these symbionts. Finally, sequence comparisons revealed no variation of the Wolbachia wsp and Rickettsia gtlA genes, but some diversity of the Cardinium 16S rRNA, both between and within populations of the three mite species. Some of the Cardinium sequences identified belonged to distantly-related clades, and the lack of association between these sequences and spider mite mitotypes suggests repeated host switching of Cardinium. Overall, our results reveal a complex community of symbionts in this system, opening the path for future studies.}, } @article {pmid29390140, year = {2018}, author = {Schweizer, G and Münch, K and Mannhaupt, G and Schirawski, J and Kahmann, R and Dutheil, JY}, title = {Positively Selected Effector Genes and Their Contribution to Virulence in the Smut Fungus Sporisorium reilianum.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {629-645}, pmid = {29390140}, issn = {1759-6653}, mesh = {Basidiomycota/*genetics ; *Genes, Fungal ; Genomics ; Multigene Family ; Phylogeny ; Plant Diseases/*microbiology ; Plants/*microbiology ; Selection, Genetic ; Ustilaginales/genetics ; Virulence Factors/genetics ; }, abstract = {Plants and fungi display a broad range of interactions in natural and agricultural ecosystems ranging from symbiosis to parasitism. These ecological interactions result in coevolution between genes belonging to different partners. A well-understood example is secreted fungal effector proteins and their host targets, which play an important role in pathogenic interactions. Biotrophic smut fungi (Basidiomycota) are well-suited to investigate the evolution of plant pathogens, because several reference genomes and genetic tools are available for these species. Here, we used the genomes of Sporisorium reilianum f. sp. zeae and S. reilianum f. sp. reilianum, two closely related formae speciales infecting maize and sorghum, respectively, together with the genomes of Ustilago hordei, Ustilago maydis, and Sporisorium scitamineum to identify and characterize genes displaying signatures of positive selection. We identified 154 gene families having undergone positive selection during species divergence in at least one lineage, among which 77% were identified in the two investigated formae speciales of S. reilianum. Remarkably, only 29% of positively selected genes encode predicted secreted proteins. We assessed the contribution to virulence of nine of these candidate effector genes in S. reilianum f. sp. zeae by deleting individual genes, including a homologue of the effector gene pit2 previously characterized in U. maydis. Only the pit2 deletion mutant was found to be strongly reduced in virulence. Additional experiments are required to understand the molecular mechanisms underlying the selection forces acting on the other candidate effector genes, as well as the large fraction of positively selected genes encoding predicted cytoplasmic proteins.}, } @article {pmid29390107, year = {2018}, author = {Seyler, LM and McGuinness, LR and Gilbert, JA and Biddle, JF and Gong, D and Kerkhof, LJ}, title = {Discerning autotrophy, mixotrophy and heterotrophy in marine TACK archaea from the North Atlantic.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy014}, pmid = {29390107}, issn = {1574-6941}, abstract = {DNA stable isotope probing (SIP) was used to track the uptake of organic and inorganic carbon sources for TACK archaea (Thaumarchaeota/Aigarchaeota/Crenarchaeota/Korarchaeota) on a cruise of opportunity in the North Atlantic. Due to water limitations, duplicate samples from the deep photic (60-115 m), the mesopelagic zones (local oxygen minimum; 215-835 m) and the bathypelagic zone (2085-2835 m) were amended with various combinations of 12C- or 13C-acetate/urea/bicarbonate to assess cellular carbon acquisition. The SIP results indicated the majority of TACK archaeal operational taxonomic units (OTUs) incorporated 13C from acetate and/or urea into newly synthesized DNA within 48 h. A small fraction (16%) of the OTUs, often representing the most dominant members of the archaeal community, were able to incorporate bicarbonate in addition to organic substrates. Only two TACK archaeal OTUs were found to incorporate bicarbonate but not urea or acetate. These results further demonstrate the utility of SIP to elucidate the metabolic capability of mesothermal archaea in distinct oceanic settings and suggest that TACK archaea play a role in organic carbon recycling in the mid-depth to deep ocean.}, } @article {pmid29390090, year = {2018}, author = {Galtier, N and Roux, C and Rousselle, M and Romiguier, J and Figuet, E and Glémin, S and Bierne, N and Duret, L}, title = {Codon Usage Bias in Animals: Disentangling the Effects of Natural Selection, Effective Population Size, and GC-Biased Gene Conversion.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1092-1103}, doi = {10.1093/molbev/msy015}, pmid = {29390090}, issn = {1537-1719}, abstract = {Selection on codon usage bias is well documented in a number of microorganisms. Whether codon usage is also generally shaped by natural selection in large organisms, despite their relatively small effective population size (Ne), is unclear. In animals, the population genetics of codon usage bias has only been studied in a handful of model organisms so far, and can be affected by confounding, nonadaptive processes such as GC-biased gene conversion and experimental artefacts. Using population transcriptomics data, we analyzed the relationship between codon usage, gene expression, allele frequency distribution, and recombination rate in 30 nonmodel species of animals, each from a different family, covering a wide range of effective population sizes. We disentangled the effects of translational selection and GC-biased gene conversion on codon usage by separately analyzing GC-conservative and GC-changing mutations. We report evidence for effective translational selection on codon usage in large-Ne species of animals, but not in small-Ne ones, in agreement with the nearly neutral theory of molecular evolution. C- and T-ending codons tend to be preferred over synonymous G- and A-ending ones, for reasons that remain to be determined. In contrast, we uncovered a conspicuous effect of GC-biased gene conversion, which is widespread in animals and the main force determining the fate of AT↔GC mutations. Intriguingly, the strength of its effect was uncorrelated with Ne.}, } @article {pmid29390087, year = {2018}, author = {Grosser, K and Ramasamy, P and Amirabad, AD and Schulz, MH and Gasparoni, G and Simon, M and Schrallhammer, M}, title = {More than the "Killer Trait": Infection with the Bacterial Endosymbiont Caedibacter taeniospiralis Causes Transcriptomic Modulation in Paramecium Host.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {646-656}, pmid = {29390087}, issn = {1759-6653}, mesh = {Gammaproteobacteria/*physiology ; Gene Expression Regulation ; Metabolic Networks and Pathways ; Paramecium/*genetics/*microbiology/physiology ; Phenotype ; Sequence Analysis, RNA ; *Symbiosis ; *Transcriptome ; }, abstract = {Endosymbiosis is a widespread phenomenon and hosts of bacterial endosymbionts can be found all-over the eukaryotic tree of life. Likely, this evolutionary success is connected to the altered phenotype arising from a symbiotic association. The potential variety of symbiont's contributions to new characteristics or abilities of host organisms are largely unstudied. Addressing this aspect, we focused on an obligate bacterial endosymbiont that confers an intraspecific killer phenotype to its host. The symbiosis between Paramecium tetraurelia and Caedibacter taeniospiralis, living in the host's cytoplasm, enables the infected paramecia to release Caedibacter symbionts, which can simultaneously produce a peculiar protein structure and a toxin. The ingestion of bacteria that harbor both components leads to the death of symbiont-free congeners. Thus, the symbiosis provides Caedibacter-infected cells a competitive advantage, the "killer trait." We characterized the adaptive gene expression patterns in symbiont-harboring Paramecium as a second symbiosis-derived aspect next to the killer phenotype. Comparative transcriptomics of infected P. tetraurelia and genetically identical symbiont-free cells confirmed altered gene expression in the symbiont-bearing line. Our results show up-regulation of specific metabolic and heat shock genes whereas down-regulated genes were involved in signaling pathways and cell cycle regulation. Functional analyses to validate the transcriptomics results demonstrated that the symbiont increases host density hence providing a fitness advantage. Comparative transcriptomics shows gene expression modulation of a ciliate caused by its bacterial endosymbiont thus revealing new adaptive advantages of the symbiosis. Caedibacter taeniospiralis apparently increases its host fitness via manipulation of metabolic pathways and cell cycle control.}, } @article {pmid29390082, year = {2018}, author = {Türkowsky, D and Jehmlich, N and Diekert, G and Adrian, L and von Bergen, M and Goris, T}, title = {An integrative overview of genomic, transcriptomic and proteomic analyses in organohalide respiration research.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy013}, pmid = {29390082}, issn = {1574-6941}, abstract = {Organohalide respiration (OHR) is a crucial process in the global halogen cycle and of interest for bioremediation. However, investigations on OHR are hampered by the restricted genetic accessibility and the poor growth yields of many organohalide-respiring bacteria (OHRB). Therefore, genomics, transcriptomics and proteomics are often used to investigate OHRB. In general, these gene expression studies are more useful when the data of the different 'omics' approaches are integrated and compared among a wide range of cultivation conditions and ideally involve several closely related OHRB. Despite the availability of a couple of proteomic and transcriptomic datasets dealing with OHRB, such approaches are currently not covered in reviews. Therefore, we here present an integrative and comparative overview of omics studies performed with the OHRB Sulfurospirillum multivorans, Dehalococcoides mccartyi, Desulfitobacterium spp. and Dehalobacter restrictus. Genes, transcripts, proteins and the regulatory and biochemical processes involved in OHR are discussed, and a comprehensive view on the unusual metabolism of D. mccartyi, which is one of the few bacteria possibly using a quinone-independent respiratory chain, is provided. Several 'omics'-derived theories on OHRB, e.g. the organohalide-respiratory chain, hydrogen metabolism, corrinoid biosynthesis or one-carbon metabolism are critically discussed on the basis of this integrative approach.}, } @article {pmid29388987, year = {2018}, author = {Daly, M}, title = {Pamela Sklar (1959-2017).}, journal = {Nature}, volume = {554}, number = {7690}, pages = {32}, doi = {10.1038/d41586-018-01382-x}, pmid = {29388987}, issn = {1476-4687}, } @article {pmid29388985, year = {2018}, author = {}, title = {The dark side of light.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {18}, doi = {10.1038/d41586-018-01422-6}, pmid = {29388985}, issn = {1476-4687}, } @article {pmid29388984, year = {2018}, author = {Perlova, T}, title = {Better mentoring stands to boost junior researchers' mental health.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {31}, doi = {10.1038/d41586-018-01286-w}, pmid = {29388984}, issn = {1476-4687}, mesh = {Humans ; *Mental Health ; *Mentoring ; Mentors ; Research Personnel ; }, } @article {pmid29388983, year = {2018}, author = {}, title = {Doomsday approaches, Moon prize cancelled and sci-fi icon dies.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {10-11}, doi = {10.1038/d41586-018-01429-z}, pmid = {29388983}, issn = {1476-4687}, } @article {pmid29388982, year = {2018}, author = {Goedhart, J}, title = {Dispense with redundant P values.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {31}, doi = {10.1038/d41586-018-01314-9}, pmid = {29388982}, issn = {1476-4687}, } @article {pmid29388980, year = {2018}, author = {Flowers, GP and Crews, CM}, title = {Regeneration writ large.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {34-35}, doi = {10.1038/d41586-017-09008-4}, pmid = {29388980}, issn = {1476-4687}, support = {F32 HD086942/HD/NICHD NIH HHS/United States ; }, mesh = {Genome ; Platyhelminths ; *Regeneration ; Urodela ; }, } @article {pmid29388979, year = {2018}, author = {Padma, TV}, title = {Anti-Darwin comments in India outrage scientists.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {16-17}, doi = {10.1038/d41586-018-01241-9}, pmid = {29388979}, issn = {1476-4687}, mesh = {*Biological Evolution ; Curriculum ; India ; *Models, Biological ; Public Opinion ; Religion and Science ; Research Personnel/*psychology ; }, } @article {pmid29388978, year = {2018}, author = {Hamylton, S}, title = {Make your science count.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {137}, doi = {10.1038/d41586-018-01386-7}, pmid = {29388978}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms ; Australia ; *Climate Change ; Communication ; Coral Reefs ; *Ecology ; *Ecosystem ; Environmental Policy/*legislation & jurisprudence ; Geologic Sediments ; *Leadership ; Research Personnel/*psychology/standards ; Societies, Scientific ; }, } @article {pmid29388977, year = {2018}, author = {}, title = {The struggle to do no harm.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {31}, doi = {10.1038/d41586-018-01423-5}, pmid = {29388977}, issn = {1476-4687}, } @article {pmid29388976, year = {2018}, author = {Carswell, C}, title = {Unique oil spill in East China Sea frustrates scientists.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {17-18}, doi = {10.1038/d41586-018-00976-9}, pmid = {29388976}, issn = {1476-4687}, mesh = {Animals ; Aquatic Organisms/drug effects ; China ; *Environmental Monitoring ; Fires ; Japan ; Larva/drug effects ; Models, Theoretical ; Natural Gas/*adverse effects/*analysis/poisoning ; Oceans and Seas ; Petroleum Pollution/adverse effects ; Plankton/drug effects ; Seawater/chemistry ; Solubility ; Time Factors ; Volatilization ; Water Movements ; Water Pollutants, Chemical/*adverse effects/*analysis/chemistry/poisoning ; }, } @article {pmid29388975, year = {2018}, author = {Brey, PT and Fontenille, D and Tang, H}, title = {Re-evaluate yellow fever risk in Asia-Pacific region.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {31}, doi = {10.1038/d41586-018-01305-w}, pmid = {29388975}, issn = {1476-4687}, mesh = {*Aedes ; Animals ; Asia ; Humans ; Pacific Islands ; Risk ; *Yellow Fever ; }, } @article {pmid29388974, year = {2018}, author = {Glausiusz, J}, title = {Owls for peace: how conservation science is reaching across borders in the Middle East.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {22-23}, doi = {10.1038/d41586-018-01388-5}, pmid = {29388974}, issn = {1476-4687}, mesh = {Animals ; *Conservation of Natural Resources ; Middle East ; *Strigiformes ; }, } @article {pmid29388971, year = {2018}, author = {Guglielmi, G}, title = {Gender bias goes away when grant reviewers focus on the science.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {14-15}, doi = {10.1038/d41586-018-01212-0}, pmid = {29388971}, issn = {1476-4687}, mesh = {Age Factors ; Canada/epidemiology ; Female ; Financing, Organized/*organization & administration/*statistics & numerical data ; Humans ; Male ; Minority Groups/statistics & numerical data ; National Institutes of Health (U.S.) ; Peer Review, Research/ethics/*methods/standards ; Racism/statistics & numerical data ; Research Personnel/education/psychology/*standards ; Sex Ratio ; Sexism/*prevention & control/*statistics & numerical data ; United States ; }, } @article {pmid29388970, year = {2018}, author = {Derrick, G}, title = {Take peer pressure out of peer review.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {7}, doi = {10.1038/d41586-018-01381-y}, pmid = {29388970}, issn = {1476-4687}, mesh = {Bias ; Confidentiality ; Consensus ; *Decision Making ; Dissent and Disputes ; Humans ; *Peer Influence ; Peer Review, Research/ethics/*methods/standards ; United Kingdom ; Universities/standards ; }, } @article {pmid29388969, year = {2018}, author = {Cardoso, F and Curigliano, G}, title = {A rude awakening from tumour cells.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {35-36}, doi = {10.1038/d41586-018-01140-z}, pmid = {29388969}, issn = {1476-4687}, mesh = {Antineoplastic Agents, Hormonal ; *Breast Neoplasms ; Humans ; Neoplasm Recurrence, Local ; Risk ; }, } @article {pmid29388968, year = {2018}, author = {Perkel, JM}, title = {Data visualization tools drive interactivity and reproducibility in online publishing.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {133-134}, doi = {10.1038/d41586-018-01322-9}, pmid = {29388968}, issn = {1476-4687}, mesh = {Algorithms ; *Computer Graphics ; *Internet ; Open Access Publishing ; *Publishing ; Reproducibility of Results ; *Research Report ; *Software ; }, } @article {pmid29388967, year = {2018}, author = {Beckwith, REJ}, title = {Reactive carbon species tamed for synthesis.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {36-38}, doi = {10.1038/d41586-018-01308-7}, pmid = {29388967}, issn = {1476-4687}, mesh = {*Carbon ; }, } @article {pmid29388966, year = {2018}, author = {Maxmen, A}, title = {As Cape Town water crisis deepens, scientists prepare for 'Day Zero'.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {13-14}, doi = {10.1038/d41586-018-01134-x}, pmid = {29388966}, issn = {1476-4687}, mesh = {Adolescent ; Animals ; Animals, Laboratory ; Cities ; Conservation of Water Resources/methods/*trends ; *Disaster Planning ; *Droughts ; Female ; Humans ; Hygiene ; *Laboratories ; Public Health/*methods ; Recycling ; *Research Personnel/psychology ; Resource Allocation/methods/*trends ; South Africa ; Time Factors ; Universities ; Water Supply/*methods ; }, } @article {pmid29388965, year = {2018}, author = {Oppenheimer, SB}, title = {Include mentoring skills in hiring and promotion criteria.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {31}, doi = {10.1038/d41586-018-01311-y}, pmid = {29388965}, issn = {1476-4687}, mesh = {Humans ; *Mentoring ; *Mentors ; Personnel Selection ; }, } @article {pmid29388964, year = {2018}, author = {}, title = {Nature journals tighten rules on non-financial conflicts.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {6}, doi = {10.1038/d41586-018-01420-8}, pmid = {29388964}, issn = {1476-4687}, mesh = {*Authorship ; Bias ; *Conflict of Interest/economics ; Disclosure/*ethics ; Peer Review, Research ; *Periodicals as Topic ; Research Personnel/*ethics/psychology ; }, } @article {pmid29388963, year = {2018}, author = {Sharpe, M and Chalder, T and Stone, J}, title = {Don't reject evidence from CFS therapies.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {31}, doi = {10.1038/d41586-018-01285-x}, pmid = {29388963}, issn = {1476-4687}, support = {G0200434//Medical Research Council/United Kingdom ; }, } @article {pmid29388962, year = {2018}, author = {}, title = {The serendipity test.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {5}, doi = {10.1038/d41586-018-01405-7}, pmid = {29388962}, issn = {1476-4687}, mesh = {Penicillins ; Research/*classification/*economics ; Research Support as Topic/*organization & administration ; United Kingdom ; X-Rays ; }, } @article {pmid29388961, year = {2018}, author = {Brown, E and Woolston, C}, title = {Why science blogging still matters.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {135-137}, doi = {10.1038/d41586-018-01414-6}, pmid = {29388961}, issn = {1476-4687}, } @article {pmid29388960, year = {2018}, author = {}, title = {The scientist who predicted ice-sheet collapse - 50 years ago.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {5-6}, doi = {10.1038/d41586-018-01390-x}, pmid = {29388960}, issn = {1476-4687}, mesh = {Antarctic Regions ; Forecasting ; Fossil Fuels/statistics & numerical data ; Global Warming/*history/prevention & control ; History, 20th Century ; History, 21st Century ; History, Ancient ; *Ice Cover ; Seawater/analysis ; }, } @article {pmid29388959, year = {2018}, author = {Ignacio-Espinoza, JC and Fuhrman, JA}, title = {A non-tailed twist in the viral tale.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {38-39}, doi = {10.1038/d41586-018-00923-8}, pmid = {29388959}, issn = {1476-4687}, } @article {pmid29388958, year = {2018}, author = {}, title = {A bioinformatics workshop in a box.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {134}, doi = {10.1038/d41586-018-01424-4}, pmid = {29388958}, issn = {1476-4687}, mesh = {*Computational Biology ; Humans ; }, } @article {pmid29388957, year = {2018}, author = {Callaway, E}, title = {Israeli fossils are the oldest modern humans ever found outside of Africa.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {15-16}, doi = {10.1038/d41586-018-01261-5}, pmid = {29388957}, issn = {1476-4687}, mesh = {Africa/ethnology ; Animals ; Caves ; China ; *Fossils ; History, Ancient ; Human Migration/*history ; Humans ; Israel ; Jaw/anatomy & histology ; Morocco ; Neanderthals/anatomy & histology ; Phylogeography ; Time Factors ; Tooth/anatomy & histology ; }, } @article {pmid29388956, year = {2018}, author = {Huadong, G}, title = {Steps to the digital Silk Road.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {25-27}, doi = {10.1038/d41586-018-01303-y}, pmid = {29388956}, issn = {1476-4687}, mesh = {Africa, Eastern ; Agriculture ; Air Pollutants/analysis ; Asia ; Commerce ; Conservation of Natural Resources ; *Developing Countries ; *Ecosystem ; *Environmental Monitoring ; Industry ; Information Dissemination ; Middle East ; *Satellite Imagery ; Science ; }, } @article {pmid29388955, year = {2018}, author = {Lallensack, R}, title = {How warp-speed evolution is transforming ecology.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {19-21}, doi = {10.1038/d41586-018-01400-y}, pmid = {29388955}, issn = {1476-4687}, mesh = {Animals ; *Biological Evolution ; Ecology/*methods ; *Ecosystem ; Ecuador ; Extinction, Biological ; Finches/anatomy & histology/physiology ; Genes, Viral ; Insecta/physiology ; Observation ; Rotifera/physiology ; Smegmamorpha/genetics/physiology ; Time Factors ; }, } @article {pmid29388954, year = {2018}, author = {Shakun, JD}, title = {Pollen weighs in on a climate conundrum.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {39-40}, doi = {10.1038/d41586-018-00943-4}, pmid = {29388954}, issn = {1476-4687}, mesh = {*Allergens ; Climate ; *Pollen ; Seasons ; }, } @article {pmid29388953, year = {2018}, author = {Wang, Z and Herraiz, AG and Del Hoyo, AM and Suero, MG}, title = {Generating carbyne equivalents with photoredox catalysis.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {86-91}, doi = {10.1038/nature25185}, pmid = {29388953}, issn = {1476-4687}, abstract = {Carbon has the unique ability to bind four atoms and form stable tetravalent structures that are prevalent in nature. The lack of one or two valences leads to a set of species-carbocations, carbanions, radicals and carbenes-that is fundamental to our understanding of chemical reactivity. In contrast, the carbyne-a monovalent carbon with three non-bonded electrons-is a relatively unexplored reactive intermediate; the design of reactions involving a carbyne is limited by challenges associated with controlling its extreme reactivity and the lack of efficient sources. Given the innate ability of carbynes to form three new covalent bonds sequentially, we anticipated that a catalytic method of generating carbynes or related stabilized species would allow what we term an 'assembly point' disconnection approach for the construction of chiral centres. Here we describe a catalytic strategy that generates diazomethyl radicals as direct equivalents of carbyne species using visible-light photoredox catalysis. The ability of these carbyne equivalents to induce site-selective carbon-hydrogen bond cleavage in aromatic rings enables a useful diazomethylation reaction, which underpins sequencing control for the late-stage assembly-point functionalization of medically relevant agents. Our strategy provides an efficient route to libraries of potentially bioactive molecules through the installation of tailored chiral centres at carbon-hydrogen bonds, while complementing current translational late-stage functionalization processes. Furthermore, we exploit the dual radical and carbene character of the generated carbyne equivalent in the direct transformation of abundant chemical feedstocks into valuable chiral molecules.}, } @article {pmid29388952, year = {2018}, author = {Marsicek, J and Shuman, BN and Bartlein, PJ and Shafer, SL and Brewer, S}, title = {Reconciling divergent trends and millennial variations in Holocene temperatures.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {92-96}, doi = {10.1038/nature25464}, pmid = {29388952}, issn = {1476-4687}, mesh = {*Climate ; Europe ; Fossils ; History, 15th Century ; History, 16th Century ; History, 17th Century ; History, 18th Century ; History, 19th Century ; History, 20th Century ; History, Ancient ; Ice Cover ; *Models, Theoretical ; North America ; Pollen ; Seasons ; Stochastic Processes ; *Temperature ; }, abstract = {Cooling during most of the past two millennia has been widely recognized and has been inferred to be the dominant global temperature trend of the past 11,700 years (the Holocene epoch). However, long-term cooling has been difficult to reconcile with global forcing, and climate models consistently simulate long-term warming. The divergence between simulations and reconstructions emerges primarily for northern mid-latitudes, for which pronounced cooling has been inferred from marine and coastal records using multiple approaches. Here we show that temperatures reconstructed from sub-fossil pollen from 642 sites across North America and Europe closely match simulations, and that long-term warming, not cooling, defined the Holocene until around 2,000 years ago. The reconstructions indicate that evidence of long-term cooling was limited to North Atlantic records. Early Holocene temperatures on the continents were more than two degrees Celsius below those of the past two millennia, consistent with the simulated effects of remnant ice sheets in the climate model Community Climate System Model 3 (CCSM3). CCSM3 simulates increases in 'growing degree days'-a measure of the accumulated warmth above five degrees Celsius per year-of more than 300 kelvin days over the Holocene, consistent with inferences from the pollen data. It also simulates a decrease in mean summer temperatures of more than two degrees Celsius, which correlates with reconstructed marine trends and highlights the potential importance of the different subseasonal sensitivities of the records. Despite the differing trends, pollen- and marine-based reconstructions are correlated at millennial-to-centennial scales, probably in response to ice-sheet and meltwater dynamics, and to stochastic dynamics similar to the temperature variations produced by CCSM3. Although our results depend on a single source of palaeoclimatic data (pollen) and a single climate-model simulation, they reinforce the notion that climate models can adequately simulate climates for periods other than the present-day. They also demonstrate that amplified warming in recent decades increased temperatures above the mean of any century during the past 11,000 years.}, } @article {pmid29388951, year = {2018}, author = {Akhilesh, K and Pappu, S and Rajapara, HM and Gunnell, Y and Shukla, AD and Singhvi, AK}, title = {Early Middle Palaeolithic culture in India around 385-172 ka reframes Out of Africa models.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {97-101}, doi = {10.1038/nature25444}, pmid = {29388951}, issn = {1476-4687}, mesh = {Africa ; Animals ; Europe ; Fossils ; History, Ancient ; *Hominidae ; Human Migration/*history ; Humans ; India ; Technology/*history ; *Tool Use Behavior ; }, abstract = {Luminescence dating at the stratified prehistoric site of Attirampakkam, India, has shown that processes signifying the end of the Acheulian culture and the emergence of a Middle Palaeolithic culture occurred at 385 ± 64 thousand years ago (ka), much earlier than conventionally presumed for South Asia. The Middle Palaeolithic continued at Attirampakkam until 172 ± 41 ka. Chronologies of Middle Palaeolithic technologies in regions distant from Africa and Europe are crucial for testing theories about the origins and early evolution of these cultures, and for understanding their association with modern humans or archaic hominins, their links with preceding Acheulian cultures and the spread of Levallois lithic technologies. The geographic location of India and its rich Middle Palaeolithic record are ideally suited to addressing these issues, but progress has been limited by the paucity of excavated sites and hominin fossils as well as by geochronological constraints. At Attirampakkam, the gradual disuse of bifaces, the predominance of small tools, the appearance of distinctive and diverse Levallois flake and point strategies, and the blade component all highlight a notable shift away from the preceding Acheulian large-flake technologies. These findings document a process of substantial behavioural change that occurred in India at 385 ± 64 ka and establish its contemporaneity with similar processes recorded in Africa and Europe. This suggests complex interactions between local developments and ongoing global transformations. Together, these observations call for a re-evaluation of models that restrict the origins of Indian Middle Palaeolithic culture to the incidence of modern human dispersals after approximately 125 ka.}, } @article {pmid29388950, year = {2018}, author = {Silvi, M and Melchiorre, P}, title = {Enhancing the potential of enantioselective organocatalysis with light.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {41-49}, doi = {10.1038/nature25175}, pmid = {29388950}, issn = {1476-4687}, mesh = {Catalysis/radiation effects ; Chemistry Techniques, Synthetic/*methods ; Chemistry, Organic/*methods ; Coenzymes/metabolism/radiation effects ; Electrons ; Oxidation-Reduction/radiation effects ; Photochemistry/*methods ; Stereoisomerism ; }, abstract = {Organocatalysis-catalysis mediated by small chiral organic molecules-is a powerful technology for enantioselective synthesis, and has extensive applications in traditional ionic, two-electron-pair reactivity domains. Recently, organocatalysis has been successfully combined with photochemical reactivity to unlock previously inaccessible reaction pathways, thereby creating new synthetic opportunities. Here we describe the historical context, scientific reasoning and landmark discoveries that were essential in expanding the functions of organocatalysis to include one-electron-mediated chemistry and excited-state reactivity.}, } @article {pmid29388549, year = {2018}, author = {Yan, ZF and Lin, P and Won, KH and Li, CT and Park, G and Chin, B and Kook, M and Wang, QJ and Yi, TH}, title = {Sphingomonas rhizophila sp. nov., isolated from rhizosphere of Hibiscus syriacus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {681-686}, doi = {10.1099/ijsem.0.002566}, pmid = {29388549}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Hibiscus/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Spermidine/chemistry ; Sphingomonas/*classification/genetics/isolation & purification ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile, rod-shaped, catalase-positive and oxidase-positive bacteria (THG-T61T), was isolated from rhizosphere of Hibiscus syriacus. Growth occurred at 10-37 °C (optimum 25-30 °C), at pH 5.0-9.0 (optimum 7.0) and in the presence of 0-2.0 % NaCl (optimum without NaCl supplement). Based on 16S rRNA gene sequence analysis, the nearest phylogenetic neighbours of strain THG-T61T were identified as Sphingomonas ginsengisoli KCTC 12630T (97.9 %), Sphingomonas jaspsi DSM 18422T (97.8 %), Sphingomonas astaxanthinifaciens NBRC 102146T (97.4 %), Sphingomonassediminicola KCTC 12629T (97.2 %), 'Sphingomonas swuensis' KCTC 12336 (97.1 %) and Sphingomonas daechungensis KCTC 23718T (96.9 %). The isoprenoid quinone was ubiquinone-10 (Q-10). The major fatty acids were C16 : 0, C17 : 1ω6c, summed feature 4 (iso-C15 : 0 2-OH and/or C16 : 1ω7c) and summed feature 7 (C18 : 1ω7c, C18 : 1ω9t and/or C18 : 1ω12t). The polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, sphingoglycolipid, one unidentified lipid, one unidentified phospholipid, one unidentified glycolipid and one unidentified phosphoglycolipid. The polyamine was homospermidine. The DNA G+C content of strain THG-T61T was 65.6 mol%. The DNA-DNA relatedness values between strain THG-T61T and its closest reference strains were less than 49.2 %, which is lower than the threshold value of 70 %. Therefore, strain THG-T61T represents a novel species of the genus Sphingomonas, for which the name Sphingomonas rhizophila sp. nov. is proposed. The type strain is THG-T61T (=KACC 19189T=CCTCC AB 2016245T).}, } @article {pmid29388548, year = {2018}, author = {Jiang, F and Danzeng, W and Zhang, Y and Zhang, Y and Jiang, L and Liu, J and Lu, L and Fan, W and Peng, F}, title = {Hymenobacter rubripertinctus sp. nov., isolated from Antarctic tundra soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {663-668}, doi = {10.1099/ijsem.0.002563}, pmid = {29388548}, issn = {1466-5034}, mesh = {Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; *Tundra ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A red-pigmented, Gram-reaction-negative, aerobic, non-motile and rod-shaped bacterium, designated NY03-3-30T, was isolated from a soil sample collected from Inexpressible Island, Northern Victoria Land of the Antarctic Ross Orogen, and subjected to a polyphasic taxonomic study. Growth occurred at 4-28 °C (optimum 20 °C) and at pH 6.0-9.0 (optimum pH 7.0). Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain NY03-3-30T belonged to the genus Hymenobacter in the family Cytophagaceae. 16S rRNA gene sequence similarities between strain NY03-3-30T and the type strains of Hymenobacter species with validly published names ranged from 92.7 to 96.2 %. Strain NY03-3-30T contained summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0, C16 : 0, C16 : 1ω5c, anteiso-C15 : 0 and summed feature 4 (iso-C17 : 1-I and/or anteiso-C17 : 1-B) as major cellular fatty acids, MK-7 as the respiratory quinone and phosphatidylethanolamine as the main polar lipid. The DNA G+C content of strain NY03-3-30T was 59.4 mol%. On the basis of phylogenetic, physiological and chemotaxonomic data, strain NY03-3-30T is considered to represent a novel species of genus Hymenobacter, for which the name Hymenobacter rubripertinctus sp. nov. is proposed. The type strain is NY03-3-30T (=CCTCC AB 2017095T=KCTC 62163T).}, } @article {pmid29388546, year = {2018}, author = {Subhash, Y and Lee, SS}, title = {Roseomonas deserti sp. nov., isolated from crude oil contaminated desert sand.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {675-680}, doi = {10.1099/ijsem.0.002565}, pmid = {29388546}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Desert Climate ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Kuwait ; Methylobacteriaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Petroleum/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Silicon Dioxide ; }, abstract = {Two dark pink pigmented bacterial strains (M3T and M11) were isolated from crude oil contaminated desert sand from Kuwait. Both strains were Gram-stain-negative and small-rod to oval-shaped bacteria. Strains M3T and M11 grew at 13-42 °C (optimum, 30-35 °C) and pH 6.5-9.0 (optimum, 7.0-7.5). No additional NaCl was required for the growth of both strains. The genomic DNA G+C content of strains M3T and M11 were 69.5 and 69.0 mol%, respectively. Both strains were closely related and the mean DNA-DNA hybridization value was 92±1 %. 16S rRNA gene sequence comparisons of both strains indicated that they belong to the genus Roseomonas. Strains M3T and M11 had a sequence similarity of 97.3 and 97.4 % with Roseomonas oryzae JC288T, respectively. Both strains had <97 % 16S rRNA gene sequence similarity with other members of the genus Roseomonas. Strain M3T showed 18±2 and 13±2 % reassociation (based on DNA-DNA hybridization) with R. oryzae KCTC 42542T and Roseomonas cervicalis KACC 11686T, respectively. The major cellular fatty acids (>5 %) were identified as C18 : 1ω6c/C18 : 1ω7c, C16 : 1ω6c/C16 : 1ω7c and C16 : 0 in both strains. Both strains showed diphosphatidylglycerol, phosphatidylglycerol, phosphatidyl-ethanolamine, phosphatidylcholine and unidentified glycolipid as major polar lipids. Based on distinct phenotypic, genotypic and phylogenetic differences from the previously described taxa, we propose the classification of strains M3T and M11 as representative of a novel species in the genus Roseomonas, for which the name Roseomonas deserti sp. nov. is suggested. The type strain is M3T (=KEMB 2255-459T=JCM 31275T).}, } @article {pmid29388545, year = {2018}, author = {Wu, H and Liu, B and Shao, Y and Ou, X and Huang, F}, title = {Thermostaphylospora grisealba gen. nov., sp. nov., isolated from mushroom compost and transfer of Thermomonospora chromogena Zhang et al. 1998 to Thermostaphylospora chromogena comb. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {602-608}, doi = {10.1099/ijsem.0.002551}, pmid = {29388545}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; *Agaricales ; Bacterial Typing Techniques ; Base Composition ; China ; Composting ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel thermophilic actinomycete, designated strain 3-12XT, was isolated from mushroom compost in Guangxi University, Nanning, China. The novel isolate contained meso-diaminopimelic acid as the diagnostic diamino acid and the whole-cell sugars were glucose and ribose. The predominant menaquinones were MK-9(H4) and MK-9(H6). The polar phospholipids were diphosphatidylglycerol, hydroxy-phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylethanolamine, phosphatidylinositol, phosphatidylinositol mannoside, ninhydrin-positive phosphoglycolipids and glycolipids. Major fatty acids were so-C16 : 0 and C17 : 0. The G+C content of the genomic DNA was 74.6 %. The 16S rRNA gene sequence analysis showed that the closest phylogenetic neighbour of strain 3-12XT was Thermomonospora chromogena ATCC 43196T (97.0 %), other closely related strains all belonged to the family Streptosporangiaceae and showed more than 6 % divergence. The chemotaxonomic characteristics of strain 3-12XT were significantly different from Thermomonospora chromogena ATCC 43196T and DNA-DNA hybridization showed low relatedness (48.6-55.6 %) between them, so they should be different species. Thermomonospora chromogena was removed from the genus Thermomonospora by Zhang et al. 1998 on the basis of phylogenetic, chemotaxonomic and phenotypic evidence, but its taxonomic position remains uncertain. Based on the phenotypic and phylogenetic data, strain 3-12XT represents a novel species in a new genus in the family Streptosporangiaceae. The name Thermostaphylospora griseoalba gen. nov., sp. nov. is proposed. The type strain of Thermostaphylospora grisealba is 3-12XT (=DSM 46781T=CGMCC 4.7160T). We also propose transferring Thermomonospora chromogenaZhang et al. 1998 to Thermostaphylospora chromogena comb. nov. (type strain ATCC 43196T=JCM 6244T).}, } @article {pmid29388544, year = {2018}, author = {Christiansen, L and Bech, PK and Schultz-Johansen, M and Martens, HJ and Stougaard, P}, title = {Colwellia echini sp. nov., an agar- and carrageenan-solubilizing bacterium isolated from sea urchin.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {687-691}, doi = {10.1099/ijsem.0.002568}, pmid = {29388544}, issn = {1466-5034}, mesh = {Agar ; Alginates ; Alteromonadaceae/*classification/genetics/isolation & purification ; Animals ; Bacterial Typing Techniques ; Base Composition ; Carrageenan ; DNA, Bacterial/genetics ; Denmark ; Fatty Acids/chemistry ; Gammaproteobacteria ; Glucans ; Glucuronic Acid ; Hexuronic Acids ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sepharose ; Sequence Analysis, DNA ; Strongylocentrotus/*microbiology ; Ubiquinone/chemistry ; }, abstract = {A novel bacterial strain, A3T, was isolated from the intestines of the sea urchin Strongylocentrotus droebachiensis collected in Øresund, Denmark. The strain was Gram-reaction-negative, rod-shaped and facultatively anaerobic, and displayed growth at 5-25 °C (optimum 20 °C), pH 7-9 (optimum at pH 7) and 1-6 % (w/v) NaCl (optimum 3 %). Furthermore, strain A3T grew on agar, agarose, κ-carrageenan, alginate and laminarin as sole carbon source. Complete liquefaction of agar and κ-carrageenan was observed on solid plate media as a result of enzymatic activities. Major fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The respiratory quinones were determined to be ubiquinones Q-8 (92 %) and Q-7 (8 %), and polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol. The DNA G+C content was 36.9 mol%. Phylogenetical analyses based on the 16S rRNA gene showed that the bacterium was affiliated with the genus Colwellia within the Alteromonadaceae of the Gammaproteobacteria. The level of 16S rRNA gene sequence similarity between strain A3T and its closest relatives in the genus Colwellia (C. psychrerythraea ATCC 27364T and C. asteriadis KMD 002T) was 97.5 %. The average nucleotide identity between strain A3T and other members of Colwellia was 78.6-80.5 %, and DNA-DNA hybridization prediction revealed values of less than 23 % relatedness between strain A3T and other Colwellia species. The phenotypic, phylogenetic and genomic analyses support the hypothesis that strain A3T represents a novel species of the genus Colwellia, for which the name Colwellia echini sp. nov. is proposed. The type strain is A3T (=LMG 30125T=NCIMB 15095T).}, } @article {pmid29388543, year = {2018}, author = {Park, S and Choi, SJ and Won, SM and Yoon, JH}, title = {Jannaschia confluentis sp. nov., isolated from the junction between the ocean and a freshwater spring.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {669-674}, doi = {10.1099/ijsem.0.002564}, pmid = {29388543}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fresh Water/*microbiology ; Nucleic Acid Hybridization ; Phosphatidylcholines/chemistry ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and ovoid or rod-shaped bacterial strain, designated JSSK-16T, was isolated from the place where the ocean and a freshwater spring meet at Jeju Island, South Korea. Strain JSSK-16T grew optimally at 30 °C, at pH 6.5-8.0 and in the presence of 2.0-4.0 % (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain JSSK-16T joined the clade comprising the type strains of Jannaschia species. Strain JSSK-16T exhibited 16S rRNA gene sequence similarity values of 97.5 and 97.1 % to the type strains of Jannaschia donghaensis and Jannaschia faecimaris, respectively, and of 94.1-96.6 % to the type strains of the other Jannaschia species. Strain JSSK-16T contained Q-10 as the predominant ubiquinone and C18 : 1ω7c, 11-methyl C18 : 1ω7c and C18 : 0 as the major fatty acids. The major polar lipids detected in strain JSSK-16T were phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. The DNA G+C content of strain JSSK-16T was 68.8 mol% and its DNA-DNA relatedness values with the type strains of J. donghaensis and J. faecimaris were 18 and 12, respectively. Differential phenotypic properties, together with its phylogenetic and genetic distinctiveness, revealed that strain JSSK-16T is separated from recognized species of the genus Jannaschia. On the basis of the data presented, strain JSSK-16T is considered to represent a novel species of the genus Jannaschia, for which the name Jannaschia confluentis sp. nov. is proposed. The type strain is JSSK-16T (=KACC 19436T=KCTC 62137T=NBRC 113018T).}, } @article {pmid29388542, year = {2018}, author = {Jin, QW and Hu, YH and Sun, L}, title = {Alteromonas oceani sp. nov., isolated from deep-sea sediment of a hydrothermal field.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {657-662}, doi = {10.1099/ijsem.0.002560}, pmid = {29388542}, issn = {1466-5034}, mesh = {Alteromonas/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Hydrothermal Vents/*microbiology ; Papua New Guinea ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel rod-shaped, Gram-stain-negative, aerobic bacterium, designated S35T, was isolated from deep-sea sediment collected from the Pacmanus hydrothermal field, Manus Basin, Papua New Guinea. Strain S35T grew optimally at 28 °C, at pH 7.0-8.0 and in the presence of 2.0 % (w/v) NaCl. 16S rRNA gene sequence analysis indicated that strain S35T shared 97.38-98.55% similarity with the type strains of Alteromonas lipolytica, Alteromonas mediterranea and Aestuariibacterhalophilus. Phylogenetic analysis showed that strain S35T belonged to the genus Alteromonas. The strain contained ubiquinone-8 as the predominant respiratory lipoquinone. Summed feature 3 (C16 : 1ω7c and/or C16 : 1ω7c), summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0 were the major fatty acids. The DNA G+C content of strain S35T was 51.3 mol%. These results indicated that strain S35T represents a novel species of the genus Alteromonas, for which the name Alteromonas oceani sp. nov. (type strain S35T=KCTC 52449T=CGMCC 1.16029T) is proposed.}, } @article {pmid29388541, year = {2018}, author = {Cho, GY and Lee, JC and Whang, KS}, title = {Erratum: Aliifodinibius salicampi sp. nov., a moderately halophilic bacterium isolated from a grey saltern.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {692}, doi = {10.1099/ijsem.0.002572}, pmid = {29388541}, issn = {1466-5034}, } @article {pmid29388539, year = {2018}, author = {Kaur, M and Singh, H and Sharma, S and Mishra, S and Tanuku, NRS and Pinnaka, AK}, title = {Sphingobacterium bovisgrunnientis sp. nov., isolated from yak milk.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {636-642}, doi = {10.1099/ijsem.0.002562}, pmid = {29388539}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Cattle/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; India ; Milk/*microbiology ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sphingobacterium/*classification/genetics/isolation & purification ; }, abstract = {A novel Gram-negative, rod shaped, non-motile bacterium, designated strain YK2T, was isolated from yak milk from Leh, India. The strain was positive for oxidase- and catalase-activities and negative for starch hydrolysis, nitrate reduction, citrate utilization, urease, lysine decarboxylase and ornithine decarboxylase activities. The predominant fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH, iso-C17 : 1ω9c and C16 : 1ω7c and/or C16 : 1ω6c and/or iso-C15 : 0 2-OH (summed feature 3). The major polar lipids were phosphatidylethanolamine, one unidentified aminophospholipid and six unidentified lipids. The DNA G+C content of the strain was 38.9 mol%. The 16S rRNA gene sequence analysis indicated that strain YK2T was a member of the genus Sphingobacterium and closely related to Sphingobacterium alimentarium and Sphingobacterium composti with pair-wise sequence similarity of 98.3 and 97.9 %, respectively. The sequence similarity to other members of the genus Sphingobacterium was between 92.6 to 96.3 %. Phylogenetic analysis showed that strain YK2T clustered with Sphingobacterium alimentarium and together clustered with Sphingobacterium composti. DNA-DNA hybridization of strain YK2T with Sphingobacterium alimentarium WCC 4521T and Sphingobacterium composti T5-12T showed a relatedness of only 38 and 54 %, respectively. Based on the phenotypic characteristics and on phylogenetic inference, it appears that strain YK2T represents a novel species of the genus Sphingobacterium, for which the name Sphingobacterium bovisgrunnientis sp. nov. is proposed. The type strain of Sphingobacterium bovisgrunnientis sp. nov. is YK2T (=MTCC 12631T=KCTC 52685T=JCM 31951T).}, } @article {pmid29388536, year = {2018}, author = {Zhao, B and Hu, Q and Guo, X and Liao, Z and Sarmiento, F and Mesbah, NM and Yan, Y and Li, J and Wiegel, J}, title = {Natronolimnobius aegyptiacus sp. nov., an extremely halophilic alkalithermophilic archaeon isolated from the athalassohaline Wadi An Natrun, Egypt.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {498-506}, doi = {10.1099/ijsem.0.002524}, pmid = {29388536}, issn = {1466-5034}, mesh = {Base Composition ; DNA, Archaeal/genetics ; Egypt ; Euryarchaeota/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {An obligately aerobic extremely halophilic alkalithermophilic archaeon, strain JW/NM-HA 15T, was isolated from the sediments of Wadi An Natrun in Egypt. Phylogenetic analysis based on 16S rRNA and rpoB' gene sequences indicated that it belongs to the family Natrialbaceae of the order Natrialbales. The closest relatives were Natronolimnobius baerhuensis IHC-005T and Natronolimnobius innermongolicus N-1311T (95.3 and 94.5 % 16S rRNA gene sequence similarity, respectively). Genome relatedness between strain JW/NM-HA 15T and its neighbours was evaluated using average nucleotide identity, digital DNA-DNA hybridization and average amino acid identity with the values of 75.7-85.0, 18.1-20.0, and 70.2-71.0%, respectively. Cells were obligately aerobic, rod-shaped, non-motile, Gram-stain-negative and chemo-organotrophic. The strain grew in the presence of 2.57 M to saturating Na+ (optimum 3.25-4.60 M Na+), at pH55 °C 7.5-10.5 (optimum pH55 °C 9.0-9.5), and at 30-56 °C (optimum 52 °C). The major polar lipids consisted of phosphatidylglycerol, methylated phosphatidylglycerolphosphate and two phospholipids. The complete genome size of strain JW/NM-HA 15T is approximately 3.93 Mb, with a DNA G+C content of 64.1 mol%. On the basis of phylogenetic features, genomic relatedness, phenotypic and chemotaxonomic data, strain JW/NM-HA 15T was thus considered to represent a novel species within the genus Natronolimnobius, for which the name Natronolimnobius aegyptiacus sp. nov. is proposed. The type strain is JW/NM-HA 15T (=ATCC BAA-2088T =DSM 23470T).}, } @article {pmid29388535, year = {2018}, author = {Hu, D and Wang, L and Lai, Q and Sun, F and Shao, Z}, title = {Marivivens niveibacter sp. nov., isolated from the seawater of tropical mangrove.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {570-574}, doi = {10.1099/ijsem.0.002544}, pmid = {29388535}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*chemistry ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Wetlands ; }, abstract = {A novel bacterial strain, designated HSLHS2T, was isolated from the seawater of a tropical mangrove forest. Cells of strain HSLHS2T were found to be aerobic, Gram-stain-negative, non-flagellated, non-motile, short rods. Oxidase- and catalase-positive. Growth was observed at 5-40 °C (optimum, 35 °C), at pH 6.0-10.0 (optimum pH 8.0) and in 0-10 % NaCl (optimum 2 %, w/v). Strain HSLHS2T shared highest 16S rRNA gene sequence similarity with Celeribacter halophilus ZXM137T (95.4 %), but formed a distinct phyletic lineage and coherent phylogenetic cluster associated with Marivivens donghaensis AM-4T (95.1 %). The dominant fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0. The respiratory quinone was determined to be Q-10. The polar lipids comprised phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminolipids, four unidentified lipids, five unidentified phospholipids. The DNA G+C contents was 54.6 mol%. The combined genotypic and phenotypic data indicated that strain HSLHS2T represents a novel species of the genus Marivivens, for which the name Marivivensniveibacter sp. nov. is proposed. The type strain is HSLHS2T (=KCTC 52588T=MCCC 1A06712T).}, } @article {pmid29388534, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations, and new taxonomic opinions have appeared in volume 67, part 11, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {471-473}, doi = {10.1099/ijsem.0.002532}, pmid = {29388534}, issn = {1466-5034}, } @article {pmid29387161, year = {2018}, author = {Sudo, M and Takahashi, D and Andow, DA and Suzuki, Y and Yamanaka, T}, title = {Optimal management strategy of insecticide resistance under various insect life histories: Heterogeneous timing of selection and interpatch dispersal.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {271-283}, pmid = {29387161}, issn = {1752-4571}, abstract = {Although theoretical studies have shown that the mixture strategy, which uses multiple toxins simultaneously, can effectively delay the evolution of insecticide resistance, whether it is the optimal management strategy under different insect life histories and insecticide types remains unknown. To test the robustness of this management strategy over different life histories, we developed a series of simulation models that cover almost all the diploid insect types and have the same basic structure describing pest population dynamics and resistance evolution with discrete time steps. For each of two insecticidal toxins, independent one-locus two-allele autosomal inheritance of resistance was assumed. The simulations demonstrated the optimality of the mixture strategy either when insecticide efficacy was incomplete or when some part of the population disperses between patches before mating. The rotation strategy, which uses one insecticide on one pest generation and a different one on the next, did not differ from sequential usage in the time to resistance, except when dominance was low. It was the optimal strategy when insecticide efficacy was high and premating selection and dispersal occur.}, } @article {pmid29387160, year = {2018}, author = {Alves, ML and Belo, M and Carbas, B and Brites, C and Paulo, M and Mendes-Moreira, P and Brites, C and Bronze, MDR and Šatović, Z and Vaz Patto, MC}, title = {Long-term on-farm participatory maize breeding by stratified mass selection retains molecular diversity while improving agronomic performance.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {254-270}, pmid = {29387160}, issn = {1752-4571}, abstract = {Modern maize breeding programs gave rise to genetically uniform varieties that can affect maize's capacity to cope with increasing climate unpredictability. Maize populations, genetically more heterogeneous, can evolve and better adapt to a broader range of edaphic-climatic conditions. These populations usually suffer from low yields; it is therefore desirable to improve their agronomic performance while maintaining their valuable diversity levels. With this objective, a long-term participatory breeding/on-farm conservation program was established in Portugal. In this program, maize populations were subject to stratified mass selection. This work aimed to estimate the effect of on-farm stratified mass selection on the agronomic performance, quality, and molecular diversity of two historical maize populations. Multilocation field trials, comparing the initial populations with the derived selection cycles, showed that this selection methodology led to agronomic improvement for one of the populations. The molecular diversity analysis, using microsatellites, revealed that overall genetic diversity in both populations was maintained throughout selection. The comparison of quality parameters between the initial populations and the derived selection cycles was made using kernel from a common-garden experiment. This analysis showed that the majority of the quality traits evaluated progressed erratically over time. In conclusion, this breeding approach, through simple and low-cost methodologies, proved to be an alternative strategy for genetic resources' on-farm conservation.}, } @article {pmid29387159, year = {2018}, author = {Zaviezo, T and Retamal, R and Urvois, T and Fauvergue, X and Blin, A and Malausa, T}, title = {Effects of inbreeding on a gregarious parasitoid wasp with complementary sex determination.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {243-253}, pmid = {29387159}, issn = {1752-4571}, abstract = {Inbreeding and inbreeding depression are processes in small populations of particular interest for a range of human activities such as animal breeding, species conservation, or pest management. In particular, biological control programs should benefit from a thorough understanding of the causes and consequences of inbreeding because natural enemies experience repetitive bottlenecks during importation, laboratory rearing, and introduction. Predicting the effect of inbreeding in hymenopteran parasitoid wasps, frequently used in biological control programs, is nonetheless a difficult endeavor. In haplodiploid parasitoids, the purge of deleterious alleles via haploid males should reduce genetic load, but if these species also have complementary sex determination (CSD), abnormal diploid males will be produced, which may jeopardize the success of biological control introductions. Mastrus ridens is such a parasitoid wasp with CSD, introduced to control the codling moth, Cydia pomonella (L.). We studied its life history traits in the laboratory under two conditions: inbred (full-sib) and outbred (nonsib) crosses, across five generations, to examine the consequences of inbreeding in this species. We found that in inbred lines, nonreproducing females live less, the number of daughters produced was lower, and sex ratio (proportion of males) and proportion of diploid males were higher. Diploid males were able to produce fertile daughters, but fewer than haploid males. Lineage survival was similar for inbred and outbred lines across the five generations. The most significant decrease in fitness was thus a consequence of the production of diploid males, but this effect was not as extreme as in most other species with CSD, due to the fertility of diploid males. This study highlights the importance of determining the type of sex determination in parasitoid wasps used for biological control, and the importance of maintaining genetic diversity in species with CSD when importation or augmentation is the goal.}, } @article {pmid29387158, year = {2018}, author = {Gugger, PF and Liang, CT and Sork, VL and Hodgskiss, P and Wright, JW}, title = {Applying landscape genomic tools to forest management and restoration of Hawaiian koa (Acacia koa) in a changing environment.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {231-242}, pmid = {29387158}, issn = {1752-4571}, abstract = {Identifying and quantifying the importance of environmental variables in structuring population genetic variation can help inform management decisions for conservation, restoration, or reforestation purposes, in both current and future environmental conditions. Landscape genomics offers a powerful approach for understanding the environmental factors that currently associate with genetic variation, and given those associations, where populations may be most vulnerable under future environmental change. Here, we applied genotyping by sequencing to generate over 11,000 single nucleotide polymorphisms from 311 trees and then used nonlinear, multivariate environmental association methods to examine spatial genetic structure and its association with environmental variation in an ecologically and economically important tree species endemic to Hawaii, Acacia koa. Admixture and principal components analyses showed that trees from different islands are genetically distinct in general, with the exception of some genotypes that match other islands, likely as the result of recent translocations. Gradient forest and generalized dissimilarity models both revealed a strong association between genetic structure and mean annual rainfall. Utilizing a model for projected future climate on the island of Hawaii, we show that predicted changes in rainfall patterns may result in genetic offset, such that trees no longer may be genetically matched to their environment. These findings indicate that knowledge of current and future rainfall gradients can provide valuable information for the conservation of existing populations and also help refine seed transfer guidelines for reforestation or replanting of koa throughout the state.}, } @article {pmid29387157, year = {2018}, author = {Käch, H and Mathé-Hubert, H and Dennis, AB and Vorburger, C}, title = {Rapid evolution of symbiont-mediated resistance compromises biological control of aphids by parasitoids.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {220-230}, pmid = {29387157}, issn = {1752-4571}, abstract = {There is growing interest in biological control as a sustainable and environmentally friendly way to control pest insects. Aphids are among the most detrimental agricultural pests worldwide, and parasitoid wasps are frequently employed for their control. The use of asexual parasitoids may improve the effectiveness of biological control because only females kill hosts and because asexual populations have a higher growth rate than sexuals. However, asexuals may have a reduced capacity to track evolutionary change in their host populations. We used a factorial experiment to compare the ability of sexual and asexual populations of the parasitoid Lysiphlebus fabarum to control caged populations of black bean aphids (Aphis fabae) of high and low clonal diversity. The aphids came from a natural population, and one-third of the aphid clones harbored Hamiltonella defensa, a heritable bacterial endosymbiont that increases resistance to parasitoids. We followed aphid and parasitoid population dynamics for 3 months but found no evidence that the reproductive mode of parasitoids affected their effectiveness as biocontrol agents, independent of host clonal diversity. Parasitoids failed to control aphids in most cases, because their introduction resulted in strong selection for clones protected by H. defensa. The increasingly resistant aphid populations escaped control by parasitoids, and we even observed parasitoid extinctions in many cages. The rapid evolution of symbiont-conferred resistance in turn imposed selection on parasitoids. In cages where asexual parasitoids persisted until the end of the experiment, they became dominated by a single genotype able to overcome the protection provided by H. defensa. Thus, there was evidence for parasitoid counteradaptation, but it was generally too slow for parasitoids to regain control over aphid populations. It appears that when pest aphids possess defensive symbionts, the presence of parasitoid genotypes able to overcome symbiont-conferred resistance is more important for biocontrol success than their reproductive mode.}, } @article {pmid29387156, year = {2018}, author = {Thorn, MW and Morbey, YE}, title = {Egg size and the adaptive capacity of early life history traits in Chinook salmon (Oncorhynchus tshawytscha).}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {205-219}, pmid = {29387156}, issn = {1752-4571}, abstract = {Offspring traits are greatly influenced by maternal effects, and these maternal effects may provide an important pathway through which populations can adapt to changing thermal environments. We investigated the effect of egg size on the among- and within-population variation in early life history traits among introduced Great Lakes Chinook salmon (Oncorhynchus tshawytscha) populations under varying thermal conditions. We reared Chinook salmon from three populations in a common-garden hatchery study at 6.5, 9.4, and 15.2°C and measured a variety of fitness-related traits during development. We found that most of the among-population variation in early life history traits was explained by egg size. However, the contribution of egg size to the among-population variation decreased with an increase in temperature suggesting that other effects, such as genetic, contribute at high temperature. Within populations, egg size explained much of the dam variance and maternal effect for traits in every temperature, whereas egg size generally had little to no influence on the sire variance and heritability. Overall, our results demonstrate the significant contribution egg size makes to shaping early life history phenotypes among and within populations, and suggest that egg size is an important pathway through which offspring phenotypes can evolve on contemporary timescales.}, } @article {pmid29387155, year = {2018}, author = {Mondon, A and Owens, GL and Poverene, M and Cantamutto, M and Rieseberg, LH}, title = {Gene flow in Argentinian sunflowers as revealed by genotyping-by-sequencing data.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {193-204}, pmid = {29387155}, issn = {1752-4571}, abstract = {Gene flow can have several different applied consequences, ranging from extinction to the escape of transgenes to the evolution of weedy or invasive lineages. Here, we describe patterns of hybridization and gene flow involving domesticated and wild sunflowers in Argentina. To address the risks of introgression of variants from the cultivated sunflower into invasive wild Helianthus, we used genotyping-by-sequencing (GBS) to genotype 182 samples from 11 sites in Argentina, along with previously published data from samples from the native range (North America), to determine the native source populations of the Argentinian samples and to detect admixture. We unexpectedly discovered two distinctive forms of H. petiolaris in Argentina, one from H. petiolaris subsp. petiolaris as expected, but the other from an unknown source. Extensive admixture was observed among Argentinian sunflowers, largely confirming phenotypic predictions. While many hybrids are F1s, there were signals consistent with introgression from the domesticated sunflower into H. petiolaris. Whether this introgression is incidental or a causal driver of invasiveness is not yet clear, but it seems likely that genes found in the domesticated sunflower genome (whether engineered or not) will quickly find their way into wild Argentinian sunflower populations.}, } @article {pmid29387154, year = {2018}, author = {He, MH and Li, DL and Zhu, W and Wu, EJ and Yang, LN and Wang, YP and Waheed, A and Zhan, J}, title = {Slow and temperature-mediated pathogen adaptation to a nonspecific fungicide in agricultural ecosystem.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {182-192}, pmid = {29387154}, issn = {1752-4571}, abstract = {The spread of antimicrobial resistance and global change in air temperature represent two major phenomena that are exerting a disastrous impact on natural and social issues but investigation of the interaction between these phenomena in an evolutionary context is limited. In this study, a statistical genetic approach was used to investigate the evolution of antimicrobial resistance in agricultural ecosystem and its association with local air temperature, precipitation, and UV radiation. We found no resistance to mancozeb, a nonspecific fungicide widely used in agriculture for more than half a century, in 215 Alternaria alternata isolates sampled from geographic locations along a climatic gradient and cropping system representing diverse ecotypes in China, consistent with low resistance risk in many nonspecific fungicides. Genetic variance accounts for ~35% of phenotypic variation, while genotype-environment interaction is negligible, suggesting that heritability plays a more important role in the evolution of resistance to mancozeb in plant pathogens than phenotypic plasticity. We also found that tolerance to mancozeb in agricultural ecosystem is under constraining selection and significantly associated with local air temperature, possibly resulting from a pleiotropic effect of resistance with thermal and other ecological adaptations. The implication of these results for fungicide and other antimicrobial management in the context of global warming is discussed.}, } @article {pmid29387153, year = {2018}, author = {MacLachlan, IR and Yeaman, S and Aitken, SN}, title = {Growth gains from selective breeding in a spruce hybrid zone do not compromise local adaptation to climate.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {166-181}, pmid = {29387153}, issn = {1752-4571}, abstract = {Hybrid zones contain extensive standing genetic variation that facilitates rapid responses to selection. The Picea glauca × Picea engelmannii hybrid zone in western Canada is the focus of tree breeding programs that annually produce ~90 million reforestation seedlings. Understanding the direct and indirect effects of selective breeding on adaptive variation is necessary to implement assisted gene flow (AGF) polices in Alberta and British Columbia that match these seedlings with future climates. We decomposed relationships among hybrid ancestry, adaptive traits, and climate to understand the implications of selective breeding for climate adaptations and AGF strategies. The effects of selection on associations among hybrid index estimated from ~6,500 SNPs, adaptive traits, and provenance climates were assessed for ~2,400 common garden seedlings. Hybrid index differences between natural and selected seedlings within breeding zones were small in Alberta (average +2%), but larger and more variable in BC (average -7%, range -24% to +1%), slightly favoring P. glauca ancestry. The average height growth gain of selected seedlings over natural seedlings within breeding zones was 36% (range 12%-86%). Clines in growth with temperature-related variables were strong, but differed little between selected and natural populations. Seedling hybrid index and growth trait associations with evapotranspiration-related climate variables were stronger in selected than in natural seedlings, indicating possible preadaptation to drier future climates. Associations among cold hardiness, hybrid ancestry, and cold-related climate variables dominated signals of local adaptation and were preserved in breeding populations. Strong hybrid ancestry-phenotype-climate associations suggest that AGF will be necessary to match interior spruce breeding populations with shifting future climates. The absence of antagonistic selection responses among traits and maintenance of cold adaptation in selected seedlings suggests breeding populations can be safely redeployed using AGF prescriptions similar to those of natural populations.}, } @article {pmid29387152, year = {2018}, author = {Sylvester, EVA and Bentzen, P and Bradbury, IR and Clément, M and Pearce, J and Horne, J and Beiko, RG}, title = {Applications of random forest feature selection for fine-scale genetic population assignment.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {153-165}, pmid = {29387152}, issn = {1752-4571}, abstract = {Genetic population assignment used to inform wildlife management and conservation efforts requires panels of highly informative genetic markers and sensitive assignment tests. We explored the utility of machine-learning algorithms (random forest, regularized random forest and guided regularized random forest) compared with FST ranking for selection of single nucleotide polymorphisms (SNP) for fine-scale population assignment. We applied these methods to an unpublished SNP data set for Atlantic salmon (Salmo salar) and a published SNP data set for Alaskan Chinook salmon (Oncorhynchus tshawytscha). In each species, we identified the minimum panel size required to obtain a self-assignment accuracy of at least 90% using each method to create panels of 50-700 markers Panels of SNPs identified using random forest-based methods performed up to 7.8 and 11.2 percentage points better than FST-selected panels of similar size for the Atlantic salmon and Chinook salmon data, respectively. Self-assignment accuracy ≥90% was obtained with panels of 670 and 384 SNPs for each data set, respectively, a level of accuracy never reached for these species using FST-selected panels. Our results demonstrate a role for machine-learning approaches in marker selection across large genomic data sets to improve assignment for management and conservation of exploited populations.}, } @article {pmid29387151, year = {2018}, author = {You, W and Henneberg, M}, title = {Cancer incidence increasing globally: The role of relaxed natural selection.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {140-152}, pmid = {29387151}, issn = {1752-4571}, abstract = {Cancer incidence increase has multiple aetiologies. Mutant alleles accumulation in populations may be one of them due to strong heritability of many cancers. The opportunity for the operation of natural selection has decreased in the past ~150 years because of reduction in mortality and fertility. Mutation-selection balance may have been disturbed in this process and genes providing background for some cancers may have been accumulating in human gene pools. Worldwide, based on the WHO statistics for 173 countries the index of the opportunity for selection is strongly inversely correlated with cancer incidence in peoples aged 0-49 years and in people of all ages. This relationship remains significant when gross domestic product per capita (GDP), life expectancy of older people (e50), obesity, physical inactivity, smoking and urbanization are kept statistically constant for fifteen (15) of twenty-seven (27) individual cancers incidence rates. Twelve (12) cancers which are not correlated with relaxed natural selection after considering the six potential confounders are largely attributable to external causes like viruses and toxins. Ratios of the average cancer incidence rates of the 10 countries with lowest opportunities for selection to the average cancer incidence rates of the 10 countries with highest opportunities for selection are 2.3 (all cancers at all ages), 2.4 (all cancers in 0-49 years age group), 5.7 (average ratios of strongly genetically based cancers) and 2.1 (average ratios of cancers with less genetic background).}, } @article {pmid29387150, year = {2018}, author = {Grossen, C and Biebach, I and Angelone-Alasaad, S and Keller, LF and Croll, D}, title = {Population genomics analyses of European ibex species show lower diversity and higher inbreeding in reintroduced populations.}, journal = {Evolutionary applications}, volume = {11}, number = {2}, pages = {123-139}, pmid = {29387150}, issn = {1752-4571}, abstract = {Restoration of lost species ranges to their native distribution is key for the survival of endangered species. However, reintroductions often fail and long-term genetic consequences are poorly understood. Alpine ibex (Capra ibex) are wild goats that recovered from <100 individuals to ~50,000 within a century by population reintroductions. We analyzed the population genomic consequences of the Alpine ibex reintroduction strategy. We genotyped 101,822 genomewide single nucleotide polymorphism loci in 173 Alpine ibex, the closely related Iberian ibex (Capra pyrenaica) and domestic goat (Capra hircus). The source population of all Alpine ibex maintained genetic diversity comparable to Iberian ibex, which experienced less severe bottlenecks. All reintroduced Alpine ibex populations had individually and combined lower levels of genetic diversity than the source population. The reintroduction strategy consisted of primary reintroductions from captive breeding and secondary reintroductions from established populations. This stepwise reintroduction strategy left a strong genomic footprint of population differentiation, which increased with subsequent rounds of reintroductions. Furthermore, analyses of genomewide runs of homozygosity showed recent inbreeding primarily in individuals of reintroduced populations. We showed that despite the rapid census recovery, Alpine ibex carry a persistent genomic signature of their reintroduction history. We discuss how genomic monitoring can serve as an early indicator of inbreeding.}, } @article {pmid29386397, year = {2018}, author = {Ye, J and Witter, MP and Moser, MB and Moser, EI}, title = {Entorhinal fast-spiking speed cells project to the hippocampus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1627-E1636}, pmid = {29386397}, issn = {1091-6490}, mesh = {Animals ; Entorhinal Cortex/*cytology/metabolism ; GABAergic Neurons/cytology/metabolism ; Hippocampus/*cytology/metabolism ; Male ; Parvalbumins/metabolism ; Rats, Long-Evans ; Space Perception ; }, abstract = {The mammalian positioning system contains a variety of functionally specialized cells in the medial entorhinal cortex (MEC) and the hippocampus. In order for cells in these systems to dynamically update representations in a way that reflects ongoing movement in the environment, they must be able to read out the current speed of the animal. Speed is encoded by speed-responsive cells in both MEC and hippocampus, but the relationship between the two populations has not been determined. We show here that many entorhinal speed cells are fast-spiking putative GABAergic neurons. Using retrograde viral labeling from the hippocampus, we find that a subset of these fast-spiking MEC speed cells project directly to hippocampal areas. This projection contains parvalbumin (PV) but not somatostatin (SOM)-immunopositive cells. The data point to PV-expressing GABAergic projection neurons in MEC as a source for widespread speed modulation and temporal synchronization in entorhinal-hippocampal circuits for place representation.}, } @article {pmid29386396, year = {2018}, author = {Tan, YT and Ye, L and Xie, F and Beyer, AI and Muench, MO and Wang, J and Chen, Z and Liu, H and Chen, SJ and Kan, YW}, title = {Respecifying human iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells with a single factor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2180-2185}, pmid = {29386396}, issn = {1091-6490}, support = {P01 DK088760/DK/NIDDK NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; *Erythroid Cells ; Gene Expression Regulation/physiology ; Hematopoietic Stem Cells/*physiology ; Humans ; Induced Pluripotent Stem Cells/*drug effects ; Mice ; Myeloid-Lymphoid Leukemia Protein/genetics/*metabolism ; Oncogene Proteins, Fusion/genetics/*metabolism ; Teratoma ; }, abstract = {Derivation of human hematopoietic stem cells (HSCs) from induced pluripotent stem cells (iPSCs) offers considerable promise for cell therapy, disease modeling, and drug screening. However, efficient derivation of functional iPSC-derived HSCs with in vivo engraftability and multilineage potential remains challenging. Here, we demonstrate a tractable approach for respecifying iPSC-derived blood cells into highly engraftable hematopoietic stem and progenitor cells (HSPCs) through transient expression of a single transcription factor, MLL-AF4 These induced HSPCs (iHSPCs) derived from iPSCs are able to fully reconstitute the human hematopoietic system in the recipient mice without myeloid bias. iHSPCs are long-term engraftable, but they are also prone to leukemic transformation during the long-term engraftment period. On the contrary, primary HSPCs with the same induction sustain the long-term engraftment without leukemic transformation. These findings demonstrate the feasibility of activating the HSC network in human iPSC-derived blood cells through expression of a single factor and suggest iHSPCs are more genomically instable than primary HSPCs, which merits further attention.}, } @article {pmid29386395, year = {2018}, author = {Taggart, D and Andreou, T and Scott, KJ and Williams, J and Rippaus, N and Brownlie, RJ and Ilett, EJ and Salmond, RJ and Melcher, A and Lorger, M}, title = {Anti-PD-1/anti-CTLA-4 efficacy in melanoma brain metastases depends on extracranial disease and augmentation of CD8+ T cell trafficking.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1540-E1549}, pmid = {29386395}, issn = {1091-6490}, support = {//Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Antibodies, Monoclonal/*pharmacology ; Brain Neoplasms/immunology/secondary/*therapy ; CD8-Positive T-Lymphocytes/*immunology ; Female ; Granzymes/immunology ; Lymphocytes, Tumor-Infiltrating/*immunology ; Melanoma, Experimental/immunology/pathology/*therapy ; Mice ; Mice, Inbred C57BL ; Programmed Cell Death 1 Receptor/immunology ; Skin Neoplasms/immunology/secondary/therapy ; T-Lymphocytes, Cytotoxic/*immunology ; T-Lymphocytes, Regulatory/*immunology ; Tumor Burden ; Tumor Cells, Cultured ; }, abstract = {Inhibition of immune checkpoints programmed death 1 (PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA-4) on T cells results in durable antitumor activity in melanoma patients. Despite high frequency of melanoma brain metastases (BrM) and associated poor prognosis, the activity and mechanisms of immune checkpoint inhibitors (ICI) in metastatic tumors that develop within the "immune specialized" brain microenvironment, remain elusive. We established a melanoma tumor transplantation model with intracranial plus extracranial (subcutaneous) tumor, mimicking the clinically observed coexistence of metastases inside and outside the brain. Strikingly, intracranial ICI efficacy was observed only when extracranial tumor was present. Extracranial tumor was also required for ICI-induced increase in CD8+ T cells, macrophages, and microglia in brain tumors, and for up-regulation of immune-regulatory genes. Combined PD-1/CTLA-4 blockade had a superior intracranial efficacy over the two monotherapies. Cell depletion studies revealed that NK cells and CD8+ T cells were required for intracranial anti-PD-1/anti-CTLA-4 efficacy. Rather than enhancing CD8+ T cell activation and expansion within intracranial tumors, PD-1/CTLA-4 blockade dramatically (∼14-fold) increased the trafficking of CD8+ T cells to the brain. This was mainly through the peripheral expansion of homing-competent effector CD8+ T cells and potentially further enhanced through up-regulation of T cell entry receptors intercellular adhesion molecule 1 and vascular adhesion molecule 1 on tumor vasculature. Our study indicates that extracranial activation/release of CD8+ T cells from PD-1/CTLA-4 inhibition and potentiation of their recruitment to the brain are paramount to the intracranial anti-PD-1/anti-CTLA-4 activity, suggesting augmentation of these processes as an immune therapy-enhancing strategy in metastatic brain cancer.}, } @article {pmid29386394, year = {2018}, author = {Kim, DH and Kim, YJ and Adams, ME}, title = {Endocrine regulation of airway clearance in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1535-1540}, pmid = {29386394}, issn = {1091-6490}, mesh = {Airway Obstruction/*drug therapy ; Animals ; Calcium/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster/drug effects/*physiology ; Insect Hormones/*pharmacology ; Kinins/*pharmacology ; Larva/drug effects/physiology ; Neurons/cytology/drug effects/*physiology ; Receptors, Peptide/genetics/metabolism ; Signal Transduction ; TRPA1 Cation Channel/genetics/metabolism ; Trachea/cytology/drug effects/*physiology ; }, abstract = {Fluid clearance from the respiratory system during developmental transitions is critically important for achieving optimal gas exchange in animals. During insect development from embryo to adult, airway clearance occurs episodically each time the molt is completed by performance of the ecdysis sequence, coordinated by a peptide-signaling cascade initiated by ecdysis-triggering hormone (ETH). We find that the neuropeptide Kinin (also known as Drosokinin or Leukokinin) is required for normal respiratory fluid clearance or "tracheal air-filling" in Drosophila larvae. Disruption of Kinin signaling leads to defective air-filling during all larval stages. Such defects are observed upon ablation or electrical silencing of Kinin neurons, as well as RNA silencing of the Kinin gene or the ETH receptor in Kinin neurons, indicating that ETH targets Kinin neurons to promote tracheal air-filling. A Kinin receptor mutant fly line (Lkrf02594) also exhibits tracheal air-filling defects in all larval stages. Targeted Kinin receptor silencing in tracheal epithelial cells using breathless or pickpocket (ppk) drivers compromises tracheal air-filling. On the other hand, promotion of Kinin signaling in vivo through peptide injection or Kinin neuron activation through Drosophila TrpA1 (dTrpA1) expression induces premature tracheal collapse and air-filling. Moreover, direct exposure of tracheal epithelial cells in vitro to Kinin leads to calcium mobilization in tracheal epithelial cells. Our findings strongly implicate the neuropeptide Kinin as an important regulator of airway clearance via intracellular calcium mobilization in tracheal epithelial cells of Drosophila.}, } @article {pmid29386393, year = {2018}, author = {Luan, Q and Zelter, A and MacCoss, MJ and Davis, TN and Nolen, BJ}, title = {Identification of Wiskott-Aldrich syndrome protein (WASP) binding sites on the branched actin filament nucleator Arp2/3 complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1409-E1418}, pmid = {29386393}, issn = {1091-6490}, support = {P41 GM103533/GM/NIGMS NIH HHS/United States ; R01 GM092917/GM/NIGMS NIH HHS/United States ; }, mesh = {Actin Cytoskeleton/chemistry/*metabolism ; Actin-Related Protein 2-3 Complex/chemistry/*metabolism ; Amino Acid Sequence ; Binding Sites ; Protein Binding ; *Protein Conformation ; Protein Interaction Mapping ; Saccharomyces cerevisiae/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; Sequence Homology ; Wiskott-Aldrich Syndrome Protein/chemistry/*metabolism ; }, abstract = {Arp2/3 complex nucleates branched actin filaments important for cellular motility and endocytosis. WASP family proteins are Arp2/3 complex activators that play multiple roles in branching nucleation, but little is known about the structural bases of these WASP functions, owing to an incomplete understanding of how WASP binds Arp2/3 complex. Recent data show WASP binds two sites, and biochemical and structural studies led to models in which the WASP C segment engages the barbed ends of the Arp3 and Arp2 subunits while the WASP A segment binds the back side of the complex on Arp3. However, electron microscopy reconstructions showed density for WASP inconsistent with these models on the opposite (front) side of Arp2/3 complex. Here we use chemical cross-linking and mass spectrometry (XL-MS) along with computational docking and structure-based mutational analysis to map the two WASP binding sites on the complex. Our data corroborate the barbed end and back side binding models and show one WASP binding site on Arp3, on the back side of the complex, and a second site on the bottom of the complex, spanning Arp2 and ARPC1. The XL-MS-identified cross-links rule out the front side binding model and show that the A segment of WASP binds along the bottom side of the ARPC1 subunit, instead of at the Arp2/ARPC1 interface, as suggested by FRET experiments. The identified binding sites support the Arp3 tail release model to explain WASP-mediated activating conformational changes in Arp2/3 complex and provide insight into the roles of WASP in branching nucleation.}, } @article {pmid29386392, year = {2018}, author = {Xiong, Y and Neifert, S and Karuppagounder, SS and Liu, Q and Stankowski, JN and Lee, BD and Ko, HS and Lee, Y and Grima, JC and Mao, X and Jiang, H and Kang, SU and Swing, DA and Iacovitti, L and Tessarollo, L and Dawson, TM and Dawson, VL}, title = {Robust kinase- and age-dependent dopaminergic and norepinephrine neurodegeneration in LRRK2 G2019S transgenic mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1635-1640}, pmid = {29386392}, issn = {1091-6490}, support = {K01 AG046366/AG/NIA NIH HHS/United States ; P50 AG005146/AG/NIA NIH HHS/United States ; R01 NS075839/NS/NINDS NIH HHS/United States ; P20 GM103418/GM/NIGMS NIH HHS/United States ; R01 NS082205/NS/NINDS NIH HHS/United States ; R21 NS098006/NS/NINDS NIH HHS/United States ; P50 NS038377/NS/NINDS NIH HHS/United States ; K01 AG056841/AG/NIA NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Behavior, Animal ; *Disease Models, Animal ; Dopamine/*metabolism ; Dopaminergic Neurons/metabolism/*pathology ; Humans ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/*physiology ; Male ; Mice ; Mice, Transgenic ; Motor Activity ; Mutation ; Neurodegenerative Diseases/metabolism/*pathology ; Norepinephrine/*metabolism ; alpha-Synuclein/metabolism ; }, abstract = {Mutations in LRRK2 are known to be the most common genetic cause of sporadic and familial Parkinson's disease (PD). Multiple lines of LRRK2 transgenic or knockin mice have been developed, yet none exhibit substantial dopamine (DA)-neuron degeneration. Here we develop human tyrosine hydroxylase (TH) promoter-controlled tetracycline-sensitive LRRK2 G2019S (GS) and LRRK2 G2019S kinase-dead (GS/DA) transgenic mice and show that LRRK2 GS expression leads to an age- and kinase-dependent cell-autonomous neurodegeneration of DA and norepinephrine (NE) neurons. Accompanying the loss of DA neurons are DA-dependent behavioral deficits and α-synuclein pathology that are also LRRK2 GS kinase-dependent. Transmission EM reveals that that there is an LRRK2 GS kinase-dependent significant reduction in synaptic vesicle number and a greater abundance of clathrin-coated vesicles in DA neurons. These transgenic mice indicate that LRRK2-induced DA and NE neurodegeneration is kinase-dependent and can occur in a cell-autonomous manner. Moreover, these mice provide a substantial advance in animal model development for LRRK2-associated PD and an important platform to investigate molecular mechanisms for how DA neurons degenerate as a result of expression of mutant LRRK2.}, } @article {pmid29386391, year = {2018}, author = {Sorenson, RS and Deshotel, MJ and Johnson, K and Adler, FR and Sieburth, LE}, title = {Arabidopsis mRNA decay landscape arises from specialized RNA decay substrates, decapping-mediated feedback, and redundancy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1485-E1494}, pmid = {29386391}, issn = {1091-6490}, support = {P30 CA042014/CA/NCI NIH HHS/United States ; T32 GM007464/GM/NIGMS NIH HHS/United States ; T32 HD007491/HD/NICHD NIH HHS/United States ; }, mesh = {Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Endoribonucleases/genetics/*metabolism ; Gene Expression Regulation, Plant ; RNA Caps/genetics/*metabolism ; *RNA Stability ; RNA, Messenger/genetics/*metabolism ; RNA, Plant/genetics/*metabolism ; }, abstract = {The decay of mRNA plays a vital role in modulating mRNA abundance, which, in turn, influences cellular and organismal processes. In plants and metazoans, three distinct pathways carry out the decay of most cytoplasmic mRNAs: The mRNA decapping complex, which requires the scaffold protein VARICOSE (VCS), removes a protective 5' cap, allowing for 5' to 3' decay via EXORIBONUCLEASE4 (XRN4, XRN1 in metazoans and yeast), and both the exosome and SUPPRESSOR OF VCS (SOV)/DIS3L2 degrade RNAs in the 3' to 5' direction. However, the unique biological contributions of these three pathways, and whether they degrade specialized sets of transcripts, are unknown. In Arabidopsis, the participation of SOV in RNA homeostasis is also unclear, because Arabidopsis sov mutants have a normal phenotype. We carried out mRNA decay analyses in wild-type, sov, vcs, and vcs sov seedlings, and used a mathematical modeling approach to determine decay rates and quantify gene-specific contributions of VCS and SOV to decay. This analysis revealed that VCS (decapping) contributes to decay of 68% of the transcriptome, and, while it initiates degradation of mRNAs with a wide range of decay rates, it especially contributes to decay of short-lived RNAs. Only a few RNAs were clear SOV substrates in that they decayed more slowly in sov mutants. However, 4,506 RNAs showed VCS-dependent feedback in sov that modulated decay rates, and, by inference, transcription, to maintain RNA abundances, suggesting that these RNAs might also be SOV substrates. This feedback was shown to be independent of siRNA activity.}, } @article {pmid29386390, year = {2018}, author = {Wardhana, DA and Ikeda, K and Barinda, AJ and Nugroho, DB and Qurania, KR and Yagi, K and Miyata, K and Oike, Y and Hirata, KI and Emoto, N}, title = {Family with sequence similarity 13, member A modulates adipocyte insulin signaling and preserves systemic metabolic homeostasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1529-1534}, pmid = {29386390}, issn = {1091-6490}, mesh = {Adipocytes/cytology/*metabolism ; Animals ; Female ; GTPase-Activating Proteins/*physiology ; Glucose/metabolism ; HEK293 Cells ; Homeostasis ; Humans ; Insulin/*metabolism ; Insulin Receptor Substrate Proteins/metabolism ; *Insulin Resistance ; Male ; Metabolic Diseases/*etiology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Obesity/*complications ; Signal Transduction ; }, abstract = {Adipose tissue dysfunction is causally implicated in the impaired metabolic homeostasis associated with obesity; however, detailed mechanisms underlying dysregulated adipocyte functions in obesity remain to be elucidated. Here we searched for genes that provide a previously unknown mechanism in adipocyte metabolic functions and identified family with sequence similarity 13, member A (Fam13a) as a factor that modifies insulin signal cascade in adipocytes. Fam13a was highly expressed in adipose tissue, predominantly in mature adipocytes, and its expression was substantially reduced in adipose tissues of obese compared with lean mice. We revealed that Fam13a accentuated insulin signaling by recruiting protein phosphatase 2A with insulin receptor substrate 1 (IRS1), leading to protection of IRS1 from proteasomal degradation. We further demonstrated that genetic loss of Fam13a exacerbated obesity-related metabolic disorders, while targeted activation of Fam13a in adipocytes ameliorated it in association with altered adipose tissue insulin sensitivity in mice. Our data unveiled a previously unknown mechanism in the regulation of adipocyte insulin signaling by Fam13a and identified its significant role in systemic metabolic homeostasis, shedding light on Fam13a as a pharmacotherapeutic target to treat obesity-related metabolic disorders.}, } @article {pmid29386389, year = {2018}, author = {Yao, J and Yang, F and Sun, X and Wang, S and Gan, N and Liu, Q and Liu, D and Zhang, X and Niu, D and Wei, Y and Ma, C and Luo, ZQ and Sun, Q and Jia, D}, title = {Mechanism of inhibition of retromer transport by the bacterial effector RidL.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1446-E1454}, pmid = {29386389}, issn = {1091-6490}, support = {R01 AI127465/AI/NIAID NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Endosomes/metabolism/microbiology ; GTPase-Activating Proteins/genetics/*metabolism ; HeLa Cells ; Humans ; Legionella pneumophila/*physiology ; Legionnaires' Disease/*metabolism/microbiology ; Protein Conformation ; Protein Domains ; *Protein Multimerization ; Protein Transport ; Vesicular Transport Proteins/chemistry/*metabolism ; }, abstract = {Retrograde vesicle trafficking pathways are responsible for returning membrane-associated components from endosomes to the Golgi apparatus and the endoplasmic reticulum (ER), and they are critical for maintaining organelle identity, lipid homeostasis, and many other cellular functions. The retrograde transport pathway has emerged as an important target for intravacuolar bacterial pathogens. The opportunistic pathogen Legionella pneumophila exploits both the secretory and recycling branches of the vesicle transport pathway for intracellular bacterial proliferation. Its Dot/Icm effector RidL inhibits the activity of the retromer by directly engaging retromer components. However, the mechanism underlying such inhibition remains unknown. Here we present the crystal structure of RidL in complex with VPS29, a subunit of the retromer. Our results demonstrate that RidL binds to a highly conserved hydrophobic pocket of VPS29. This interaction is critical for endosomal recruitment of RidL and for its inhibitory effects. RidL inhibits retromer activity by direct competition, in which it occupies the VPS29-binding site of the essential retromer regulator TBC1d5. The mechanism of retromer inhibition by RidL reveals a hotspot on VPS29 critical for recognition by its regulators that is also exploited by pathogens, and provides a structural basis for the development of small molecule inhibitors against the retromer.}, } @article {pmid29386388, year = {2018}, author = {Dorfman, KE and Mukamel, S}, title = {Multidimensional photon correlation spectroscopy of cavity polaritons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1451-1456}, pmid = {29386388}, issn = {1091-6490}, abstract = {The strong coupling of atoms and molecules to radiation field modes in optical cavities creates dressed matter/field states known as polaritons with controllable dynamical and energy transfer properties. We propose a multidimensional optical spectroscopy technique for monitoring polariton dynamics. The response of a two-level atom to the time-dependent coupling to a single-cavity mode is monitored through time-and-frequency-resolved single-photon coincidence measurements of spontaneous emission. Polariton population and coherence dynamics and its variation with cavity photon number and controlled by gating parameters are predicted by solving the Jaynes-Cummings model.}, } @article {pmid29386387, year = {2018}, author = {Zhou, HH and Singh, V and Johnson, SC and Wahba, G and , }, title = {Statistical tests and identifiability conditions for pooling and analyzing multisite datasets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1481-1486}, pmid = {29386387}, issn = {1091-6490}, support = {U54 AI117924/AI/NIAID NIH HHS/United States ; R01 AG040396/AG/NIA NIH HHS/United States ; P30 AG008051/AG/NIA NIH HHS/United States ; R01 EB022883/EB/NIBIB NIH HHS/United States ; UL1 RR025011/RR/NCRR NIH HHS/United States ; R01 AG021155/AG/NIA NIH HHS/United States ; P50 AG033514/AG/NIA NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Algorithms ; Alzheimer Disease/*cerebrospinal fluid ; Biomarkers/cerebrospinal fluid ; Data Interpretation, Statistical ; Databases, Factual/*statistics & numerical data ; Humans ; Middle Aged ; }, abstract = {When sample sizes are small, the ability to identify weak (but scientifically interesting) associations between a set of predictors and a response may be enhanced by pooling existing datasets. However, variations in acquisition methods and the distribution of participants or observations between datasets, especially due to the distributional shifts in some predictors, may obfuscate real effects when datasets are combined. We present a rigorous statistical treatment of this problem and identify conditions where we can correct the distributional shift. We also provide an algorithm for the situation where the correction is identifiable. We analyze various properties of the framework for testing model fit, constructing confidence intervals, and evaluating consistency characteristics. Our technical development is motivated by Alzheimer's disease (AD) studies, and we present empirical results showing that our framework enables harmonizing of protein biomarkers, even when the assays across sites differ. Our contribution may, in part, mitigate a bottleneck that researchers face in clinical research when pooling smaller sized datasets and may offer benefits when the subjects of interest are difficult to recruit or when resources prohibit large single-site studies.}, } @article {pmid29386386, year = {2018}, author = {Pierce, SB and Stewart, MD and Gulsuner, S and Walsh, T and Dhall, A and McClellan, JM and Klevit, RE and King, MC}, title = {De novo mutation in RING1 with epigenetic effects on neurodevelopment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1558-1563}, pmid = {29386386}, issn = {1091-6490}, support = {R01 GM088055/GM/NIGMS NIH HHS/United States ; R01 MH083989/MH/NIMH NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Caenorhabditis elegans/genetics/*growth & development ; Case-Control Studies ; *Epigenesis, Genetic ; *Gene Expression Regulation, Developmental ; Histones/genetics/metabolism ; Humans ; *Mutation ; Neurodevelopmental Disorders/*genetics/pathology ; Nucleosomes/metabolism ; Polycomb Repressive Complex 1/*genetics ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/metabolism ; Ubiquitination ; }, abstract = {RING1 is an E3-ubiquitin ligase that is involved in epigenetic control of transcription during development. It is a component of the polycomb repressive complex 1, and its role in that complex is to ubiquitylate histone H2A. In a 13-year-old girl with syndromic neurodevelopmental disabilities, we identified a de novo mutation, RING1 p.R95Q, which alters a conserved arginine residue in the catalytic RING domain. In vitro assays demonstrated that the mutant RING1 retains capacity to catalyze ubiquitin chain formation, but is defective in its ability to ubiquitylate histone H2A in nucleosomes. Consistent with this in vitro effect, cells of the patient showed decreased monoubiquitylation of histone H2A. We modeled the mutant RING1 in Caenorhabditis elegans by editing the comparable amino acid change into spat-3, the suggested RING1 ortholog. Animals with either the missense mutation or complete knockout of spat-3 were defective in monoubiquitylation of histone H2A and had defects in neuronal migration and axon guidance. Relevant to our patient, animals heterozygous for either the missense or knockout allele also showed neuronal defects. Our results support three conclusions: mutation of RING1 is the likely cause of a human neurodevelopmental syndrome, mutation of RING1 can disrupt histone H2A ubiquitylation without disrupting RING1 catalytic activity, and the comparable mutation in C. elegans spat-3 both recapitulates the effects on histone H2A ubiquitylation and leads to neurodevelopmental abnormalities. This role for RING1 adds to our understanding of the importance of aberrant epigenetic effects as causes of human neurodevelopmental disorders.}, } @article {pmid29386385, year = {2018}, author = {Harris, CC}, title = {Tobacco smoking, E-cigarettes, and nicotine harm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1406-1407}, pmid = {29386385}, issn = {1091-6490}, mesh = {*Electronic Nicotine Delivery Systems ; Humans ; *Nicotine ; Smoking Cessation ; Tobacco ; Tobacco Smoking ; Tobacco Use Disorder ; }, } @article {pmid29386384, year = {2018}, author = {Kyung, JW and Kim, JM and Lee, W and Ha, TY and Cha, SH and Chung, KH and Choi, DJ and Jou, I and Song, WK and Joe, EH and Kim, SH and Park, SM}, title = {DJ-1 deficiency impairs synaptic vesicle endocytosis and reavailability at nerve terminals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1629-1634}, pmid = {29386384}, issn = {1091-6490}, mesh = {Animals ; Cells, Cultured ; Endocytosis/*physiology ; Mice ; Mice, Knockout ; Mutation ; Nerve Endings/metabolism/*pathology ; Protein Deglycase DJ-1/*physiology ; Synapses/metabolism/*pathology ; Synaptic Vesicles/metabolism/*pathology ; }, abstract = {Mutations in DJ-1 (PARK7) are a known cause of early-onset autosomal recessive Parkinson's disease (PD). Accumulating evidence indicates that abnormalities of synaptic vesicle trafficking underlie the pathophysiological mechanism of PD. In the present study, we explored whether DJ-1 is involved in CNS synaptic function. DJ-1 deficiency impaired synaptic vesicle endocytosis and reavailability without inducing structural alterations in synapses. Familial mutants of DJ-1 (M26I, E64D, and L166P) were unable to rescue defective endocytosis of synaptic vesicles, whereas WT DJ-1 expression completely restored endocytic function in DJ-1 KO neurons. The defective synaptic endocytosis shown in DJ-1 KO neurons may be attributable to alterations in membrane cholesterol level. Thus, DJ-1 appears essential for synaptic vesicle endocytosis and reavailability, and impairment of this function by familial mutants of DJ-1 may be related to the pathogenesis of PD.}, } @article {pmid29386383, year = {2018}, author = {Conway, JR and Bird, G}, title = {Conceptualizing degrees of theory of mind.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1408-1410}, pmid = {29386383}, issn = {1091-6490}, mesh = {*Cognition ; Neuropsychological Tests ; Psychological Theory ; *Theory of Mind ; }, } @article {pmid29386382, year = {2018}, author = {Lenz, TL}, title = {Adaptive value of novel MHC immune gene variants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1414-1416}, pmid = {29386382}, issn = {1091-6490}, mesh = {*Major Histocompatibility Complex ; }, } @article {pmid29386381, year = {2018}, author = {Cloutier, N and Allaeys, I and Marcoux, G and Machlus, KR and Mailhot, B and Zufferey, A and Levesque, T and Becker, Y and Tessandier, N and Melki, I and Zhi, H and Poirier, G and Rondina, MT and Italiano, JE and Flamand, L and McKenzie, SE and Cote, F and Nieswandt, B and Khan, WI and Flick, MJ and Newman, PJ and Lacroix, S and Fortin, PR and Boilard, E}, title = {Platelets release pathogenic serotonin and return to circulation after immune complex-mediated sequestration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1550-E1559}, pmid = {29386381}, issn = {1091-6490}, support = {F32 HL118865/HL/NHLBI NIH HHS/United States ; R35 HL139937/HL/NHLBI NIH HHS/United States ; MOP 93575//CIHR/Canada ; U54 HL112311/HL/NHLBI NIH HHS/United States ; K01 DK111515/DK/NIDDK NIH HHS/United States ; R01 HL130054/HL/NHLBI NIH HHS/United States ; R01 AG048022/AG/NIA NIH HHS/United States ; R01 HL126547/HL/NHLBI NIH HHS/United States ; P01 HL110860/HL/NHLBI NIH HHS/United States ; }, mesh = {Adult ; Anaphylaxis/blood/genetics/*immunology ; Animals ; Antigen-Antibody Complex/*immunology ; Blood Platelets/*immunology ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Platelet Activation ; Platelet Count ; Platelet Glycoprotein GPIIb-IIIa Complex/genetics/immunology ; Receptors, IgG/genetics/immunology ; Serotonin/*immunology ; Shock, Septic/blood/genetics/*immunology ; Young Adult ; }, abstract = {There is a growing appreciation for the contribution of platelets to immunity; however, our knowledge mostly relies on platelet functions associated with vascular injury and the prevention of bleeding. Circulating immune complexes (ICs) contribute to both chronic and acute inflammation in a multitude of clinical conditions. Herein, we scrutinized platelet responses to systemic ICs in the absence of tissue and endothelial wall injury. Platelet activation by circulating ICs through a mechanism requiring expression of platelet Fcγ receptor IIA resulted in the induction of systemic shock. IC-driven shock was dependent on release of serotonin from platelet-dense granules secondary to platelet outside-in signaling by αIIbβ3 and its ligand fibrinogen. While activated platelets sequestered in the lungs and leaky vasculature of the blood-brain barrier, platelets also sequestered in the absence of shock in mice lacking peripheral serotonin. Unexpectedly, platelets returned to the blood circulation with emptied granules and were thereby ineffective at promoting subsequent systemic shock, although they still underwent sequestration. We propose that in response to circulating ICs, platelets are a crucial mediator of the inflammatory response highly relevant to sepsis, viremia, and anaphylaxis. In addition, platelets recirculate after degranulation and sequestration, demonstrating that in adaptive immunity implicating antibody responses, activated platelets are longer lived than anticipated and may explain platelet count fluctuations in IC-driven diseases.}, } @article {pmid29386380, year = {2018}, author = {Chen, Y and Wang, Z and He, Y and Yoon, YJ and Jung, J and Zhang, G and Lin, Z}, title = {Light-enabled reversible self-assembly and tunable optical properties of stable hairy nanoparticles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1391-E1400}, pmid = {29386380}, issn = {1091-6490}, abstract = {The ability to dynamically organize functional nanoparticles (NPs) via the use of environmental triggers (temperature, pH, light, or solvent polarity) opens up important perspectives for rapid and convenient construction of a rich variety of complex assemblies and materials with new structures and functionalities. Here, we report an unconventional strategy for crafting stable hairy NPs with light-enabled reversible and reliable self-assembly and tunable optical properties. Central to our strategy is to judiciously design amphiphilic star-like diblock copolymers comprising inner hydrophilic blocks and outer hydrophobic photoresponsive blocks as nanoreactors to direct the synthesis of monodisperse plasmonic NPs intimately and permanently capped with photoresponsive polymers. The size and shape of hairy NPs can be precisely tailored by modulating the length of inner hydrophilic block of star-like diblock copolymers. The perpetual anchoring of photoresponsive polymers on the NP surface renders the attractive feature of self-assembly and disassembly of NPs on demand using light of different wavelengths, as revealed by tunable surface plasmon resonance absorption of NPs and the reversible transformation of NPs between their dispersed and aggregated states. The dye encapsulation/release studies manifested that such photoresponsive NPs may be exploited as smart guest molecule nanocarriers. By extension, the star-like block copolymer strategy enables the crafting of a family of stable stimuli-responsive NPs (e.g., temperature- or pH-sensitive polymer-capped magnetic, ferroelectric, upconversion, or semiconducting NPs) and their assemblies for fundamental research in self-assembly and crystallization kinetics of NPs as well as potential applications in optics, optoelectronics, magnetic technologies, sensory materials and devices, catalysis, nanotechnology, and biotechnology.}, } @article {pmid29386379, year = {2018}, author = {Laplante, C}, title = {Resolving single-actin filaments within the contractile ring of fission yeast.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1403-1405}, pmid = {29386379}, issn = {1091-6490}, mesh = {*Actin Cytoskeleton ; Actins ; Cytokinesis ; *Schizosaccharomyces ; Schizosaccharomyces pombe Proteins ; }, } @article {pmid29386067, year = {2018}, author = {Kissinga, HD and Mwombeki, F and Said, K and Katakweba, AAS and Nonga, HE and Muhairwa, AP}, title = {Antibiotic susceptibilities of indicator bacteria Escherichia coli and Enterococci spp. isolated from ducks in Morogoro Municipality, Tanzania.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {87}, pmid = {29386067}, issn = {1756-0500}, mesh = {Ampicillin/pharmacology ; Animals ; Anti-Bacterial Agents/*pharmacology ; Asymptomatic Diseases/*epidemiology ; *Drug Resistance, Multiple, Bacterial ; Ducks ; Enterococcus/drug effects/growth & development/isolation & purification ; Escherichia coli/drug effects/growth & development/isolation & purification ; Escherichia coli Infections/epidemiology/microbiology/*veterinary ; Feces/microbiology ; Female ; Humans ; Male ; Microbial Sensitivity Tests ; Poultry ; Poultry Diseases/*epidemiology/microbiology ; Rifampin/pharmacology ; Streptococcal Infections/epidemiology/microbiology/*veterinary ; Tanzania/epidemiology ; Tetracycline/pharmacology ; Trimethoprim, Sulfamethoxazole Drug Combination/pharmacology ; }, abstract = {OBJECTIVE: To estimate the prevalence of antibiotic resistance in indicator bacteria Escherichia coli and Enterococci isolated from duck faeces in Morogoro Municipality, Tanzania.

RESULTS: Escherichia coli and Enterococcus isolation rates from ducks faeces were 91 and 100% respectively. The prevalence of antibiotic resistance of E. coli and Enterococcus was 70.3 and 42%, respectively. E. coli resistant to four antibiotics were 28 (30.8%) and showed high resistance to ampicillin (81.3), tetracycline (75.8) and trimethoprim-sulphamethoxine (62.3). Multiple antibiotic resistance of Enterococcus were more than 65%. High resistance rates shown by Enterococcus were observed in rifampin (62%), ampicillin (62%) and tetracycline (42%). Almost all farmers (92.3%) left their ducks to scavenge for food around their houses. Antibiotics used in animal treatments were oxytetracyclines, sulfonamides, penicillin dihydrostreptomycin while in humans were tetracycline, ampicillin, and amoxicillin.}, } @article {pmid29386046, year = {2018}, author = {Nelin, V and Kc, A and Andersson, O and Rana, N and Målqvist, M}, title = {Factors associated with timing of umbilical cord clamping in tertiary hospital of Nepal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {89}, pmid = {29386046}, issn = {1756-0500}, mesh = {Anemia, Iron-Deficiency/*prevention & control ; Constriction ; Cross-Sectional Studies ; *Delivery, Obstetric ; Female ; Humans ; Infant, Newborn ; Iron/*blood ; Live Birth ; Male ; Nepal ; Pregnancy ; Tertiary Care Centers ; Time Factors ; Umbilical Cord/*surgery ; }, abstract = {OBJECTIVE: Delayed umbilical cord clamping (DCC) (≥ 60 s) is recognized to improve iron status and neurodevelopment compared to early umbilical cord clamping. The aim of this study is to identify current umbilical cord clamping practice and factors determining the timing of clamping in a low-resource setting where prevalence of anemia in infants is high.

RESULTS: A cross-sectional study design including 128 observations of clinical practice in a tertiary-level maternity hospital in Kathmandu, Nepal. Overall 48% of infants received DCC. The mean and median cord clamping times were 61 ± 33 and 57 (38-79) s, respectively. Univariate analysis showed that infants born during the night shift were five times more likely to receive DCC (OR 5.6, 95% CI 1.4-38.0). Additionally, infants born after an obstetric complication were 2.5 times more likely to receive DCC (OR 2.5, 95% CI 1.2-5.3), and babies requiring ventilation had a 65% lower likelihood of receiving DCC (OR 0.35, 95% CI 0.13-0.88). Despite the existence of standard protocols for cord clamping and its proven benefit, the lack of uniformity in the timing of cord clamping reveals poor translation of clinical guidelines into clinical practice. Clinical trial registration ISRCTN97846009.}, } @article {pmid29386042, year = {2018}, author = {Kebede, A and Molla, B and Gerensea, H}, title = {Assessment of risky sexual behavior and practice among Aksum University students, Shire Campus, Shire Town, Tigray, Ethiopia, 2017.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {88}, pmid = {29386042}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Condoms/*statistics & numerical data ; Cross-Sectional Studies ; Ethiopia ; Female ; Humans ; Male ; Risk ; *Risk-Taking ; Sexual Behavior/psychology/*statistics & numerical data ; Sexual Partners/psychology ; Sexually Transmitted Diseases/prevention & control ; *Social Environment ; Students/*psychology ; Surveys and Questionnaires ; *Universities ; }, abstract = {OBJECTIVE: Having sex at early age, having multiple sexual partners, having sex while under the influence of alcohol or drugs and unprotected sexual behaviors are the common characteristics of risky sexual behavior which increases risk of individuals to sexuality and reproductive health problems. Risky sexual behavior is the most common problem in adolescents and young adults which may expose individuals for permanent social, economical, psychological and physical problem. So that this study focus on assessment of risk sexual behavior using institution based cross-sectional study design on 287 randomly selected subjects among Aksum University students.

RESULTS: Almost 60% students reported to have ever had sexual activity. Of which 86 (83.5%) and 112 (64.4%) reported having inconsistent condom use and multiple sexual partners respectively. Even though more than half of first sexual intercourse (61.5%) starts due to their desire but still peer pressure and alcohol have significant effect. Similarly the study indicated that a significant segment of students have risk sexual behaviors which increase individuals' risk of acquiring HIV/AIDS. Unless appropriate age and institutional targeted interventions exist, certain behaviors can place the university students at greater risk of HIV infection and sexually transmitted disease.}, } @article {pmid29386038, year = {2018}, author = {Garrett, LJH and Dawson, DA and Horsburgh, GJ and Reynolds, SJ}, title = {Correction to: A multiplex marker set for microsatellite typing and sexing of sooty terns Onychoprion fuscatus.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {86}, pmid = {29386038}, issn = {1756-0500}, abstract = {Following publication of the original article [1], one of the authors reported that his name was listed incorrectly, and that he would like his name to appear as S. James Reynolds instead of Silas James Reynolds. The latter format would confuse citations as all his previous publications are in the former format.}, } @article {pmid29385986, year = {2018}, author = {Khorramdelazad, M and Bar, I and Whatmore, P and Smetham, G and Bhaaskaria, V and Yang, Y and Bai, SH and Mantri, N and Zhou, Y and Ford, R}, title = {Transcriptome profiling of lentil (Lens culinaris) through the first 24 hours of Ascochyta lentis infection reveals key defence response genes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {108}, pmid = {29385986}, issn = {1471-2164}, support = {CUR00014//Grains Research and Development Corporation/International ; CUR00023//Grains Research and Development Corporation/International ; 1059775//National Health and Medical Research Council/International ; 1083450//National Health and Medical Research Council/International ; }, mesh = {Ascomycota/genetics/immunology/pathogenicity ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Genotype ; High-Throughput Nucleotide Sequencing/methods ; Immunity, Innate/*genetics ; Lens Plant/*genetics/growth & development ; Mycoses/*genetics/microbiology ; Plant Diseases/*genetics/immunology/microbiology ; }, abstract = {BACKGROUND: Ascochyta blight, caused by the fungus Ascochyta lentis, is one of the most destructive lentil diseases worldwide, resulting in over $16 million AUD annual loss in Australia alone. The use of resistant cultivars is currently considered the most effective and environmentally sustainable strategy to control this disease. However, little is known about the genes and molecular mechanisms underlying lentil resistance against A. lentis.

RESULTS: To uncover the genetic basis of lentil resistance to A. lentis, differentially expressed genes were profiled in lentil plants during the early stages of A. lentis infection. The resistant 'ILL7537' and susceptible 'ILL6002' lentil genotypes were examined at 2, 6, and 24 h post inoculation utilising high throughput RNA-Sequencing. Genotype and time-dependent differential expression analysis identified genes which play key roles in several functions of the defence response: fungal elicitors recognition and early signalling; structural response; biochemical response; transcription regulators; hypersensitive reaction and cell death; and systemic acquired resistance. Overall, the resistant genotype displayed an earlier and faster detection and signalling response to the A. lentis infection and demonstrated higher expression levels of structural defence-related genes.

CONCLUSIONS: This study presents a first-time defence-related transcriptome of lentil to A. lentis, including a comprehensive characterisation of the molecular mechanism through which defence against A. lentis is induced in the resistant lentil genotype.}, } @article {pmid29385983, year = {2018}, author = {Sendorek, DH and Caloian, C and Ellrott, K and Bare, JC and Yamaguchi, TN and Ewing, AD and Houlahan, KE and Norman, TC and Margolin, AA and Stuart, JM and Boutros, PC}, title = {Germline contamination and leakage in whole genome somatic single nucleotide variant detection.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {28}, pmid = {29385983}, issn = {1471-2105}, support = {New Investigator Award//CIHR/Canada ; R01-CA180778/NH/NIH HHS/United States ; U24-CA143858/NH/NIH HHS/United States ; New Investigator Award//Terry Fox Research Institute/International ; RS2014-01//Movember Foundation/International ; U54-HG007990/NH/NIH HHS/United States ; Large-Scale Applied Project//Genome Canada/International ; U24 CA210990/CA/NCI NIH HHS/United States ; }, mesh = {Algorithms ; *Genome, Human ; Germ Cells/*metabolism ; Humans ; Internet ; Neoplasms/genetics/pathology ; *Polymorphism, Single Nucleotide ; User-Computer Interface ; Whole Genome Sequencing ; }, abstract = {BACKGROUND: The clinical sequencing of cancer genomes to personalize therapy is becoming routine across the world. However, concerns over patient re-identification from these data lead to questions about how tightly access should be controlled. It is not thought to be possible to re-identify patients from somatic variant data. However, somatic variant detection pipelines can mistakenly identify germline variants as somatic ones, a process called "germline leakage". The rate of germline leakage across different somatic variant detection pipelines is not well-understood, and it is uncertain whether or not somatic variant calls should be considered re-identifiable. To fill this gap, we quantified germline leakage across 259 sets of whole-genome somatic single nucleotide variant (SNVs) predictions made by 21 teams as part of the ICGC-TCGA DREAM Somatic Mutation Calling Challenge.

RESULTS: The median somatic SNV prediction set contained 4325 somatic SNVs and leaked one germline polymorphism. The level of germline leakage was inversely correlated with somatic SNV prediction accuracy and positively correlated with the amount of infiltrating normal cells. The specific germline variants leaked differed by tumour and algorithm. To aid in quantitation and correction of leakage, we created a tool, called GermlineFilter, for use in public-facing somatic SNV databases.

CONCLUSIONS: The potential for patient re-identification from leaked germline variants in somatic SNV predictions has led to divergent open data access policies, based on different assessments of the risks. Indeed, a single, well-publicized re-identification event could reshape public perceptions of the values of genomic data sharing. We find that modern somatic SNV prediction pipelines have low germline-leakage rates, which can be further reduced, especially for cloud-sharing, using pre-filtering software.}, } @article {pmid29385572, year = {2018}, author = {Tilak, MK and Botero-Castro, F and Galtier, N and Nabholz, B}, title = {Illumina Library Preparation for Sequencing the GC-Rich Fraction of Heterogeneous Genomic DNA.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {616-622}, pmid = {29385572}, issn = {1759-6653}, mesh = {Animals ; Chickens/genetics ; DNA/chemistry/*genetics/isolation & purification ; *GC Rich Sequence ; *Gene Library ; Genomics/economics/methods ; High-Throughput Nucleotide Sequencing/economics/methods ; Hot Temperature ; Polymerase Chain Reaction/economics/methods ; Sequence Analysis, DNA/economics/methods ; }, abstract = {Standard Illumina libraries are biased toward sequences of intermediate GC-content. This results in an underrepresentation of GC-rich regions in sequencing projects of genomes with heterogeneous base composition, such as mammals and birds. We developed a simple, cost-effective protocol to enrich sheared genomic DNA in its GC-rich fraction by subtracting AT-rich DNA. This was achieved by heating DNA up to 90 °C before applying Illumina library preparation. We tested the new approach on chicken DNA and found that heated DNA increased average coverage in the GC-richest chromosomes by a factor up to six. Using a Taq polymerase supposedly appropriate for PCR amplification of GC-rich sequences had a much weaker effect. Our protocol should greatly facilitate sequencing and resequencing of the GC-richest regions of heterogeneous genomes, in combination with standard short-read and long-read technologies.}, } @article {pmid29385567, year = {2018}, author = {Urbarova, I and Patel, H and Forêt, S and Karlsen, BO and Jørgensen, TE and Hall-Spencer, JM and Johansen, SD}, title = {Elucidating the Small Regulatory RNA Repertoire of the Sea Anemone Anemonia viridis Based on Whole Genome and Small RNA Sequencing.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {410-426}, pmid = {29385567}, issn = {1759-6653}, mesh = {Animals ; DNA Transposable Elements ; Gene Expression Regulation ; Genetic Loci ; High-Throughput Nucleotide Sequencing ; MicroRNAs/*genetics ; RNA, Small Interfering/*genetics ; Sea Anemones/*genetics ; Sequence Analysis, RNA ; }, abstract = {Cnidarians harbor a variety of small regulatory RNAs that include microRNAs (miRNAs) and PIWI-interacting RNAs (piRNAs), but detailed information is limited. Here, we report the identification and expression of novel miRNAs and putative piRNAs, as well as their genomic loci, in the symbiotic sea anemone Anemonia viridis. We generated a draft assembly of the A. viridis genome with putative size of 313 Mb that appeared to be composed of about 36% repeats, including known transposable elements. We detected approximately equal fractions of DNA transposons and retrotransposons. Deep sequencing of small RNA libraries constructed from A. viridis adults sampled at a natural CO2 gradient off Vulcano Island, Italy, identified 70 distinct miRNAs. Eight were homologous to previously reported miRNAs in cnidarians, whereas 62 appeared novel. Nine miRNAs were recognized as differentially expressed along the natural seawater pH gradient. We found a highly abundant and diverse population of piRNAs, with a substantial fraction showing ping-pong signatures. We identified nearly 22% putative piRNAs potentially targeting transposable elements within the A. viridis genome. The A. viridis genome appeared similar in size to that of other hexacorals with a very high divergence of transposable elements resembling that of the sea anemone genus Exaiptasia. The genome encodes and expresses a high number of small regulatory RNAs, which include novel miRNAs and piRNAs. Differentially expressed small RNAs along the seawater pH gradient indicated regulatory gene responses to environmental stressors.}, } @article {pmid29385526, year = {2018}, author = {Liu, Z and Zhang, J}, title = {Human C-to-U Coding RNA Editing Is Largely Nonadaptive.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {963-969}, doi = {10.1093/molbev/msy011}, pmid = {29385526}, issn = {1537-1719}, support = {R01 GM120093/GM/NIGMS NIH HHS/United States ; }, abstract = {C-to-U RNA editing enzymatically converts the base C to U in RNA molecules and could lead to nonsynonymous changes when occurring in coding regions. Hundreds to thousands of coding sites were recently found to be C-to-U edited or editable in humans, but the biological significance of this phenomenon is elusive. Here, we test the prevailing hypothesis that nonsynonymous editing is beneficial because it provides a means for tissue- or time-specific regulation of protein function that may be hard to accomplish by mutations due to pleiotropy. The adaptive hypothesis predicts that the fraction of sites edited and the median proportion of RNA molecules edited (i.e., editing level) are both higher for nonsynonymous than synonymous editing. However, our empirical observations are opposite to these predictions. Furthermore, the frequency of nonsynonymous editing, relative to that of synonymous editing, declines as genes become functionally more important or evolutionarily more constrained, and the nonsynonymous editing level at a site is negatively correlated with the evolutionary conservation of the site. Together, these findings refute the adaptive hypothesis; they instead indicate that the reported C-to-U coding RNA editing is mostly slightly deleterious or neutral, probably resulting from off-target activities of editing enzymes. Along with similar conclusions on the more prevalent A-to-I editing and m6A modification of coding RNAs, our study suggests that, at least in humans, most events of each type of posttranscriptional coding RNA modification likely manifest cellular errors rather than adaptations, demanding a paradigm shift in the research of posttranscriptional modification.}, } @article {pmid29385525, year = {2018}, author = {Darriba, D and Flouri, T and Stamatakis, A}, title = {The State of Software for Evolutionary Biology.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1037-1046}, pmid = {29385525}, issn = {1537-1719}, abstract = {With Next Generation Sequencing data being routinely used, evolutionary biology is transforming into a computational science. Thus, researchers have to rely on a growing number of increasingly complex software. All widely used core tools in the field have grown considerably, in terms of the number of features as well as lines of code and consequently, also with respect to software complexity. A topic that has received little attention is the software engineering quality of widely used core analysis tools. Software developers appear to rarely assess the quality of their code, and this can have potential negative consequences for end-users. To this end, we assessed the code quality of 16 highly cited and compute-intensive tools mainly written in C/C++ (e.g., MrBayes, MAFFT, SweepFinder, etc.) and JAVA (BEAST) from the broader area of evolutionary biology that are being routinely used in current data analysis pipelines. Because, the software engineering quality of the tools we analyzed is rather unsatisfying, we provide a list of best practices for improving the quality of existing tools and list techniques that can be deployed for developing reliable, high quality scientific software from scratch. Finally, we also discuss journal as well as science policy and, more importantly, funding issues that need to be addressed for improving software engineering quality as well as ensuring support for developing new and maintaining existing software. Our intention is to raise the awareness of the community regarding software engineering quality issues and to emphasize the substantial lack of funding for scientific software development.}, } @article {pmid29385509, year = {2018}, author = {Mahajan, S and Agashe, D}, title = {Translational Selection for Speed Is Not Sufficient to Explain Variation in Bacterial Codon Usage Bias.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {562-576}, pmid = {29385509}, issn = {1759-6653}, mesh = {Amino Acids/genetics ; Bacteria/*genetics/growth & development ; *Codon ; Evolution, Molecular ; Gene Dosage ; Gene Expression Regulation, Bacterial ; *Protein Biosynthesis ; RNA, Bacterial/*genetics ; RNA, Ribosomal/*genetics ; RNA, Transfer/*genetics ; Selection, Genetic ; }, abstract = {Increasing growth rate across bacteria strengthens selection for faster translation, concomitantly increasing the total number of tRNA genes and codon usage bias (CUB: enrichment of specific synonymous codons in highly expressed genes). Typically, enriched codons are translated by tRNAs with higher gene copy numbers (GCN). A model of tRNA-CUB coevolution based on fast growth-associated selection on translational speed recapitulates these patterns. A key untested implication of the coevolution model is that translational selection should favor higher tRNA GCN for more frequently used amino acids, potentially weakening the effect of growth-associated selection on CUB. Surprisingly, we find that CUB saturates with increasing growth rate across γ-proteobacteria, even as the number of tRNA genes continues to increase. As predicted, amino acid-specific tRNA GCN is positively correlated with the usage of corresponding amino acids, but there is no correlation between growth rate associated changes in CUB and amino acid usage. Instead, we find that some amino acids-cysteine and those in the NNA/G codon family-show weak CUB that does not increase with growth rate, despite large variation in the corresponding tRNA GCN. We suggest that amino acid-specific variation in CUB is not explained by tRNA GCN because GCN does not influence the difference between translation times of synonymous codons as expected. Thus, selection on translational speed alone cannot fully explain quantitative variation in overall or amino acid-specific CUB, suggesting a significant role for other functional constraints and amino acid-specific codon features.}, } @article {pmid29385445, year = {2018}, author = {Gerhart, JG and Auguste Dutcher, H and Brenner, AE and Moses, AS and Grubhoffer, L and Raghavan, R}, title = {Multiple Acquisitions of Pathogen-Derived Francisella Endosymbionts in Soft Ticks.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {607-615}, pmid = {29385445}, issn = {1759-6653}, mesh = {Animals ; Argasidae/*microbiology/physiology ; Biological Evolution ; Francisella/*genetics/isolation & purification/*physiology ; Genes, Bacterial ; Gram-Negative Bacterial Infections/microbiology ; Humans ; Phylogeny ; *Symbiosis ; Virulence Factors/genetics ; }, abstract = {Bacterial endosymbionts of ticks are of interest due to their close evolutionary relationships with tick-vectored pathogens. For instance, whereas many ticks contain Francisella-like endosymbionts (FLEs), others transmit the mammalian pathogen Francisella tularensis. We recently sequenced the genome of an FLE present in the hard tick Amblyomma maculatum (FLE-Am) and showed that it likely evolved from a pathogenic ancestor. In order to expand our understanding of FLEs, in the current study we sequenced the genome of an FLE in the soft tick Ornithodoros moubata and compared it to the genomes of FLE-Am, Francisella persica-an FLE in the soft tick Argus (Persicargas) arboreus, Francisella sp. MA067296-a clinical isolate responsible for an opportunistic human infection, and F. tularensis, the established human pathogen. We determined that FLEs and MA067296 belonged to a sister taxon of mammalian pathogens, and contained inactivated versions of virulence genes present in F. tularensis, indicating that the most recent common ancestor shared by FLEs and F. tularensis was a potential mammalian pathogen. Our analyses also revealed that the two soft ticks (O. moubata and A. arboreus) probably acquired their FLEs separately, suggesting that the virulence attenuation observed in FLEs are not the consequence of a single acquisition event followed by speciation, but probably due to independent transitions of pathogenic francisellae into nonpathogenic FLEs within separate tick lineages. Additionally, we show that FLEs encode intact pathways for the production of several B vitamins and cofactors, denoting that they could function as nutrient-provisioning endosymbionts in ticks.}, } @article {pmid29385441, year = {2018}, author = {Nijenhuis, I and Stollberg, R and Lechner, U}, title = {Anaerobic microbial dehalogenation and its key players in the contaminated Bitterfeld-Wolfen megasite.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy012}, pmid = {29385441}, issn = {1574-6941}, abstract = {The megasite Bitterfeld-Wolfen is highly contaminated as a result of accidents and because of dumping of wastes from local chemical industries in the last century. A variety of contaminants including chlorinated ethenes and benzenes, hexachlorohexanes and chlorinated dioxins can still be found in the groundwater and (river) sediments. Investigations of the in situ microbial transformation of organohalides have been performed only over the last two decades at this megasite. In this review, we summarise the research on the activity of anaerobic dehalogenating bacteria at the field site in Bitterfeld-Wolfen, focusing on chlorinated ethenes, monochlorobenzene and chlorinated dioxins. Various methods and concepts were applied including ex situ cultivation and isolation, and in situ analysis of hydrochemical parameters, compound-specific stable isotope analysis of contaminants, 13C-tracer studies and molecular markers. Overall, biotransformation of organohalides is ongoing at the field site and Dehalococcoides mccartyi species play an important role in the detoxification process in the Bitterfeld-Wolfen region.}, } @article {pmid29384559, year = {2018}, author = {Rossi, M and Tascini, C and Carannante, N and Di Caprio, G and Sofia, S and Iacobello, C}, title = {Neurobrucellosis: diagnostic and clinical management of an atypical case.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {165-167}, pmid = {29384559}, issn = {1121-7138}, mesh = {Anti-Bacterial Agents/therapeutic use ; Brucellosis/drug therapy/*microbiology/*pathology ; Central Nervous System Infections/drug therapy/*microbiology/*pathology ; Humans ; Male ; Middle Aged ; }, abstract = {Brucellosis is the most common zoonosis in the world and it is caused by ingestion of foods contaminated by Brucella spp. that is able to avoid the immune system and can involve every organ system. The bacteria may affect the Central Nervous System (CNS) directly or using phagocytic cells with the way of the "Trojan Horse Model". Meningitis is the most common form of neuro-brucellosis (NB) but other neurological manifestation, with variable onset, such as severe encephalic involvement, neuropathy, vascular damage, radiculitis and hydrocephalus might happened. NB may manifest itself with an acute or chronic onset and could be the only manifestation of the infection or appearance during the systemic disease. Frequently the diagnosis might be very difficult and the clinical characteristics and the microbiological demonstration in the blood and in the CSF are necessary. The prognosis of brucella meningitis is generally better than other forms of chronic meningitis except for encephalitis or spinal cord involvement. The treatment is based on the combination of two or three antibiotics to achieve normalization of the cerebrospinal fluid parameters otherwise relapse are relatively frequent. We describe an atypical case of brucellar meningitis with many stroke-like signs, think as recurrent cerebrovascular events and treated with antithrombotic therapy, but without meningeal syndrome.}, } @article {pmid29384558, year = {2018}, author = {Biolatti, M and Dell'Oste, V and De Andrea, M and Landolfo, S}, title = {The human cytomegalovirus tegument protein pp65 (pUL83): a key player in innate immune evasion.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {87-94}, pmid = {29384558}, issn = {1121-7138}, mesh = {Cytomegalovirus/genetics/*physiology ; Gene Expression Regulation, Viral ; Humans ; Immune Evasion/*physiology ; Immunity, Innate/*physiology ; Phosphoproteins/genetics/*metabolism ; Viral Matrix Proteins/genetics/*metabolism ; }, abstract = {The germline encoded proteins serving as "pattern recognition receptors" (PRRs) constitute the earliest step in the innate immune response by recognizing the "pathogen-associated molecular patterns" (PAMPs) that comprise microbe nucleic acids and proteins usually absent from healthy hosts. Upon detection of exogenous nucleic acid two different innate immunity signaling cascades are activated. The first culminates in the production of chemokines, cytokines, and type I interferons (IFN-I), while the second leads to inflammasome complex formation. Human cytomegalovirus (HCMV), a member of the b-herpesvirus subfamily, is a widespread pathogen that infects the vast majority of the world's population. The virion has an icosahedral capsid that contains a linear dsDNA genome of approximately 240 kb, surrounded by an outer lipid envelope and a proteinaceous tegument containing several viral proteins. Despite the numerous and multifaceted antiviral effects of IFNs and cytokines, HCMV is able to invade, multiply, and establish persistent infection in healthy human hosts. To achieve this goal the virus has developed different strategies to block the IFN-I response and to alter the physiological outcomes of the IFN-inducible genes. This article focuses on HCMV tegument pp65 by reviewing its mechanisms of action in favoring virus evasion from the host innate immune response.}, } @article {pmid29383712, year = {2018}, author = {Womack, MC and Fiero, TS and Hoke, KL}, title = {Trait independence primes convergent trait loss.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {679-687}, doi = {10.1111/evo.13442}, pmid = {29383712}, issn = {1558-5646}, abstract = {The repeated, independent evolution of traits (convergent evolution) is often attributed to shared environmental selection pressures. However, developmental dependencies among traits can limit the phenotypic variation available to selection and bias evolutionary outcomes. Here, we determine how changes in developmentally correlated traits may impact convergent loss of the tympanic middle ear, a highly labile trait within toads that currently lack adaptive explanation. The middle ear's lability could reflect evolutionary trade-offs with other skull features under selection, or the middle ear may evolve independently of the rest of the skull, allowing it to be modified by active or passive processes without pleiotropic trade-offs with other skull features. We compare the skulls of 55 species (39 eared, 16 earless) within the family Bufonidae, spanning six hypothesized independent middle ear transitions. We test whether shared or lineage-specific changes in skull shape distinguish earless species from eared species and whether earless skulls lack other late-forming skull bones. We find no evidence for pleiotropic trade-offs between the middle ear and other skull structures. Instead, middle ear loss in anurans may provide a rare example of developmental independence contributing to evolutionary lability of a sensory system.}, } @article {pmid29382790, year = {2018}, author = {Gilbert, N}, title = {Inner Workings: Smart-sensor network keeps close eye on lake ecosystem.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {828-830}, pmid = {29382790}, issn = {1091-6490}, mesh = {*Ecosystem ; Environmental Monitoring/*instrumentation/*methods ; Lakes/*chemistry ; New York ; Water Pollutants/analysis ; Water Pollution/analysis ; *Water Quality ; }, } @article {pmid29382789, year = {2018}, author = {Landhuis, E}, title = {Science and Culture: Cancer researcher looks to artists for inspiration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {826-827}, doi = {10.1073/pnas.1722030115}, pmid = {29382789}, issn = {1091-6490}, mesh = {*Art ; Biomedical Research/*methods ; Culture ; Humans ; *Medicine in the Arts ; Neoplasms/*pathology ; }, } @article {pmid29382769, year = {2018}, author = {Swartz, AG and Inoue, H and Merz, TA and Hikita, Y and Raghu, S and Devereaux, TP and Johnston, S and Hwang, HY}, title = {Polaronic behavior in a weak-coupling superconductor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1475-1480}, pmid = {29382769}, issn = {1091-6490}, abstract = {The nature of superconductivity in the dilute semiconductor SrTiO3 has remained an open question for more than 50 y. The extremely low carrier densities ([Formula: see text]-[Formula: see text] cm-3) at which superconductivity occurs suggest an unconventional origin of superconductivity outside of the adiabatic limit on which the Bardeen-Cooper-Schrieffer (BCS) and Migdal-Eliashberg (ME) theories are based. We take advantage of a newly developed method for engineering band alignments at oxide interfaces and access the electronic structure of Nb-doped SrTiO3, using high-resolution tunneling spectroscopy. We observe strong coupling to the highest-energy longitudinal optic (LO) phonon branch and estimate the doping evolution of the dimensionless electron-phonon interaction strength ([Formula: see text]). Upon cooling below the superconducting transition temperature ([Formula: see text]), we observe a single superconducting gap corresponding to the weak-coupling limit of BCS theory, indicating an order of magnitude smaller coupling ([Formula: see text]). These results suggest that despite the strong normal state interaction with electrons, the highest LO phonon does not provide a dominant contribution to pairing. They further demonstrate that SrTiO3 is an ideal system to probe superconductivity over a wide range of carrier density, adiabatic parameter, and electron-phonon coupling strength.}, } @article {pmid29382768, year = {2018}, author = {Zachar, I and Szilágyi, A and Számadó, S and Szathmáry, E}, title = {Farming the mitochondrial ancestor as a model of endosymbiotic establishment by natural selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1504-E1510}, pmid = {29382768}, issn = {1091-6490}, support = {294332//European Research Council/International ; }, mesh = {Animals ; Bacteria/pathogenicity ; *Biological Evolution ; Computational Biology ; Erythrocytes/*microbiology ; Eukaryota ; Humans ; Mitochondria/*physiology ; *Models, Biological ; Predatory Behavior ; *Selection, Genetic ; Symbiosis/*physiology ; }, abstract = {The origin of mitochondria was a major evolutionary transition leading to eukaryotes, and is a hotly debated issue. It is unknown whether mitochondria were acquired early or late, and whether it was captured via phagocytosis or syntrophic integration. We present dynamical models to directly simulate the emergence of mitochondria in an ecoevolutionary context. Our results show that regulated farming of prey bacteria and delayed digestion can facilitate the establishment of stable endosymbiosis if prey-rich and prey-poor periods alternate. Stable endosymbiosis emerges without assuming any initial metabolic benefit provided by the engulfed partner, in a wide range of parameters, despite that during good periods farming is costly. Our approach lends support to the appearance of mitochondria before any metabolic coupling has emerged, but after the evolution of primitive phagocytosis by the urkaryote.}, } @article {pmid29382767, year = {2018}, author = {Madry, C and Arancibia-Cárcamo, IL and Kyrargyri, V and Chan, VTT and Hamilton, NB and Attwell, D}, title = {Effects of the ecto-ATPase apyrase on microglial ramification and surveillance reflect cell depolarization, not ATP depletion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1608-E1617}, pmid = {29382767}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 099222/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adenosine Diphosphate/metabolism ; Adenosine Triphosphatases/*metabolism ; Adenosine Triphosphate/*metabolism ; Animals ; Apyrase/metabolism ; Brain/enzymology/physiology ; Female ; Male ; Microglia/chemistry/*enzymology/physiology ; Potassium/metabolism ; Rats ; Rats, Sprague-Dawley ; }, abstract = {Microglia, the brain's innate immune cells, have highly motile processes which constantly survey the brain to detect infection, remove dying cells, and prune synapses during brain development. ATP released by tissue damage is known to attract microglial processes, but it is controversial whether an ambient level of ATP is needed to promote constant microglial surveillance in the normal brain. Applying the ATPase apyrase, an enzyme which hydrolyzes ATP and ADP, reduces microglial process ramification and surveillance, suggesting that ambient ATP/ADP maintains microglial surveillance. However, attempting to raise the level of ATP/ADP by blocking the endogenous ecto-ATPase (termed NTPDase1/CD39), which also hydrolyzes ATP/ADP, does not affect the cells' ramification or surveillance, nor their membrane currents, which respond to even small rises of extracellular [ATP] or [ADP] with the activation of K+ channels. This indicates a lack of detectable ambient ATP/ADP and ecto-ATPase activity, contradicting the results with apyrase. We resolve this contradiction by demonstrating that contamination of commercially available apyrase by a high K+ concentration reduces ramification and surveillance by depolarizing microglia. Exposure to the same K+ concentration (without apyrase added) reduced ramification and surveillance as with apyrase. Dialysis of apyrase to remove K+ retained its ATP-hydrolyzing activity but abolished the microglial depolarization and decrease of ramification produced by the undialyzed enzyme. Thus, applying apyrase affects microglia by an action independent of ATP, and no ambient purinergic signaling is required to maintain microglial ramification and surveillance. These results also have implications for hundreds of prior studies that employed apyrase to hydrolyze ATP/ADP.}, } @article {pmid29382766, year = {2018}, author = {Cersonsky, RK and van Anders, G and Dodd, PM and Glotzer, SC}, title = {Relevance of packing to colloidal self-assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1439-1444}, pmid = {29382766}, issn = {1091-6490}, abstract = {Since the 1920s, packing arguments have been used to rationalize crystal structures in systems ranging from atomic mixtures to colloidal crystals. Packing arguments have recently been applied to complex nanoparticle structures, where they often, but not always, work. We examine when, if ever, packing is a causal mechanism in hard particle approximations of colloidal crystals. We investigate three crystal structures composed of their ideal packing shapes. We show that, contrary to expectations, the ordering mechanism cannot be packing, even when the thermodynamically self-assembled structure is the same as that of the densest packing. We also show that the best particle shapes for hard particle colloidal crystals at any finite pressure are imperfect versions of the ideal packing shape.}, } @article {pmid29382765, year = {2018}, author = {Odegaard, B and Grimaldi, P and Cho, SH and Peters, MAK and Lau, H and Basso, MA}, title = {Superior colliculus neuronal ensemble activity signals optimal rather than subjective confidence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1588-E1597}, pmid = {29382765}, issn = {1091-6490}, support = {R01 NS088628/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; *Choice Behavior ; Decision Making ; Macaca mulatta ; Male ; Neurons/*physiology ; Superior Colliculi/*physiology ; }, abstract = {Recent studies suggest that neurons in sensorimotor circuits involved in perceptual decision-making also play a role in decision confidence. In these studies, confidence is often considered to be an optimal readout of the probability that a decision is correct. However, the information leading to decision accuracy and the report of confidence often covaried, leaving open the possibility that there are actually two dissociable signal types in the brain: signals that correlate with decision accuracy (optimal confidence) and signals that correlate with subjects' behavioral reports of confidence (subjective confidence). We recorded neuronal activity from a sensorimotor decision area, the superior colliculus (SC) of monkeys, while they performed two different tasks. In our first task, decision accuracy and confidence covaried, as in previous studies. In our second task, we implemented a motion discrimination task with stimuli that were matched for decision accuracy but produced different levels of confidence, as reflected by behavioral reports. We used a multivariate decoder to predict monkeys' choices from neuronal population activity. As in previous studies on perceptual decision-making mechanisms, we found that neuronal decoding performance increased as decision accuracy increased. However, when decision accuracy was matched, performance of the decoder was similar between high and low subjective confidence conditions. These results show that the SC likely signals optimal decision confidence similar to previously reported cortical mechanisms, but is unlikely to play a critical role in subjective confidence. The results also motivate future investigations to determine where in the brain signals related to subjective confidence reside.}, } @article {pmid29382764, year = {2018}, author = {Baldassi, C and Zecchina, R}, title = {Efficiency of quantum vs. classical annealing in nonconvex learning problems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1457-1462}, pmid = {29382764}, issn = {1091-6490}, abstract = {Quantum annealers aim at solving nonconvex optimization problems by exploiting cooperative tunneling effects to escape local minima. The underlying idea consists of designing a classical energy function whose ground states are the sought optimal solutions of the original optimization problem and add a controllable quantum transverse field to generate tunneling processes. A key challenge is to identify classes of nonconvex optimization problems for which quantum annealing remains efficient while thermal annealing fails. We show that this happens for a wide class of problems which are central to machine learning. Their energy landscapes are dominated by local minima that cause exponential slowdown of classical thermal annealers while simulated quantum annealing converges efficiently to rare dense regions of optimal solutions.}, } @article {pmid29382763, year = {2018}, author = {Ye, W and Han, TW and Nassar, LM and Zubia, M and Jan, YN and Jan, LY}, title = {Phosphatidylinositol-(4, 5)-bisphosphate regulates calcium gating of small-conductance cation channel TMEM16F.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1667-E1674}, pmid = {29382763}, issn = {1091-6490}, support = {R01 NS069229/NS/NINDS NIH HHS/United States ; T32 GM008568/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Anoctamins/chemistry/genetics/*metabolism ; Calcium/*metabolism ; Cell Line ; Cell Membrane/genetics/metabolism ; Humans ; Mice ; Phosphatidylinositol 4,5-Diphosphate/*metabolism ; Phospholipid Transfer Proteins/chemistry/genetics/*metabolism ; Protein Domains ; }, abstract = {TMEM16F, which is activated by elevation of intracellular calcium to trigger phospholipid scrambling and the collapse of lipid bilayer asymmetry to mediate important cellular functions such as blood coagulation, also generates a small-conductance calcium-activated cation current. How TMEM16F activation may be regulated is an open question. By recording TMEM16F Ca2+-activated current, we found that the TMEM16F Ca2+-response is desensitized by a brief exposure to high intracellular Ca2+, which is associated with depletion of phosphatidylinositol-(4, 5)-bisphosphate (PIP2) from the inner leaflet of the membrane. Application of artificial or natural PIP2 restores TMEM16F channel activity. PIP2 modulation of TMEM16F requires the presence of several positively charged amino acids in its cytoplasmic N-terminal domain. TMEM16F interaction with PIP2 works synergistically with membrane depolarization to facilitate Ca2+-gating of TMEM16F. Our study reveals the dependence of TMEM16F activity on phosphoinositides and provides one mechanism for TMEM16F activation to be strictly regulated in the cell membrane.}, } @article {pmid29382762, year = {2018}, author = {Fan, XY and Tang, BK and Xu, YY and Han, AX and Shi, KX and Wu, YK and Ye, Y and Wei, ML and Niu, C and Wong, KW and Zhao, GP and Lyu, LD}, title = {Oxidation of dCTP contributes to antibiotic lethality in stationary-phase mycobacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {2210-2215}, pmid = {29382762}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/*pharmacology ; DNA Damage/drug effects ; DNA, Bacterial ; DNA-Directed DNA Polymerase/genetics/metabolism ; Deoxycytosine Nucleotides/*metabolism ; Gene Deletion ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Enzymologic ; Humans ; Macrophages ; Mycobacterium smegmatis/*drug effects ; Mycobacterium tuberculosis/*drug effects ; Oxidation-Reduction ; Pyrophosphatases/genetics/metabolism ; Reactive Oxygen Species ; }, abstract = {Growing evidence shows that generation of reactive oxygen species (ROS) derived from antibiotic-induced metabolic perturbation contribute to antibiotic lethality. However, our knowledge of the mechanisms by which antibiotic-induced oxidative stress actually kills cells remains elusive. Here, we show that oxidation of dCTP underlies ROS-mediated antibiotic lethality via induction of DNA double-strand breaks (DSBs). Deletion of mazG-encoded 5-OH-dCTP-specific pyrophosphohydrolase potentiates antibiotic killing of stationary-phase mycobacteria, but did not affect antibiotic efficacy in exponentially growing cultures. Critically, the effect of mazG deletion on potentiating antibiotic killing is associated with antibiotic-induced ROS and accumulation of 5-OH-dCTP. Independent lines of evidence presented here indicate that the increased level of DSBs observed in the ΔmazG mutant is a dead-end event accounting for enhanced antibiotic killing. Moreover, we provided genetic evidence that 5-OH-dCTP is incorporated into genomic DNA via error-prone DNA polymerase DnaE2 and repair of 5-OH-dC lesions via the endonuclease Nth leads to the generation of lethal DSBs. This work provides a mechanistic view of ROS-mediated antibiotic lethality in stationary phase and may have broad implications not only with respect to antibiotic lethality but also to the mechanism of stress-induced mutagenesis in bacteria.}, } @article {pmid29382761, year = {2018}, author = {Vilchèze, C and Weinrick, B and Leung, LW and Jacobs, WR}, title = {Plasticity of Mycobacterium tuberculosis NADH dehydrogenases and their role in virulence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1599-1604}, pmid = {29382761}, issn = {1091-6490}, support = {R01 AI097548/AI/NIAID NIH HHS/United States ; R37 AI026170/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Drug Design ; Gene Expression Regulation, Enzymologic ; Mice ; Mice, Inbred C57BL ; *Microbial Viability ; *Mutation ; Mycobacterium tuberculosis/*enzymology/physiology ; NADH Dehydrogenase/*genetics/*metabolism ; Tuberculosis/metabolism/pathology/*virology ; *Virulence ; }, abstract = {Worldwide control of the tuberculosis (TB) epidemic has not been achieved, and the latest statistics show that the TB problem might be more endemic than previously thought. Although drugs and a TB vaccine are available, TB eradication faces the challenges of increasing occurrences of multidrug-resistant and extensively drug-resistant Mycobacterium tuberculosis (Mtb) strains. To forestall this trend, the development of drugs targeting novel pathways is actively pursued. Recently, enzymes of the electron transport chain (ETC) have been determined to be the targets of potent antimycobacterial drugs such as bedaquiline. We focused on the three NADH dehydrogenases (Ndh, NdhA, and Nuo) of the Mtb ETC with the purpose of defining their role and essentiality in Mtb Each NADH dehydrogenase was deleted in both virulent and BSL2-approved Mtb strains, from which the double knockouts ΔndhΔnuoAN and ΔndhAΔnuoAN were constructed. The ΔndhΔndhA double knockout could not be obtained, suggesting that at least one type II NADH dehydrogenase is required for Mtb growth. Δndh and ΔndhΔnuoAN showed growth defects in vitro and in vivo, susceptibility to oxidative stress, and redox alterations, while the phenotypes of ΔndhA, ΔnuoAN, and ΔndhAΔnuoAN were similar to the parental strain. Interestingly, although ΔnuoAN had no phenotype in vivo, ΔndhΔnuoAN was the most severely attenuated strain in mice, suggesting a key role for Nuo in vivo when Ndh is absent. We conclude that Ndh is the main NADH dehydrogenase of Mtb and that compounds that could target both Ndh and Nuo would be good candidates for TB drug development.}, } @article {pmid29382760, year = {2018}, author = {Dargaei, Z and Bang, JY and Mahadevan, V and Khademullah, CS and Bedard, S and Parfitt, GM and Kim, JC and Woodin, MA}, title = {Restoring GABAergic inhibition rescues memory deficits in a Huntington's disease mouse model.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1618-E1626}, pmid = {29382760}, issn = {1091-6490}, support = {MOP 496401//CIHR/Canada ; }, mesh = {Animals ; Bumetanide/administration & dosage ; Disease Models, Animal ; Female ; Hippocampus/drug effects/metabolism ; Humans ; Huntingtin Protein/genetics/metabolism ; Huntington Disease/drug therapy/genetics/*metabolism/*psychology ; Male ; *Memory/drug effects ; Memory Disorders/etiology/metabolism/*psychology ; Mice ; Mice, Transgenic ; Solute Carrier Family 12, Member 2/genetics/metabolism ; Symporters/genetics/metabolism ; gamma-Aminobutyric Acid/*metabolism ; }, abstract = {Huntington's disease (HD) is classically characterized as a movement disorder, however cognitive impairments precede the motor symptoms by ∼15 y. Based on proteomic and bioinformatic data linking the Huntingtin protein (Htt) and KCC2, which is required for hyperpolarizing GABAergic inhibition, and the important role of inhibition in learning and memory, we hypothesized that aberrant KCC2 function contributes to the hippocampal-associated learning and memory deficits in HD. We discovered that Htt and KCC2 interact in the hippocampi of wild-type and R6/2-HD mice, with a decrease in KCC2 expression in the hippocampus of R6/2 and YAC128 mice. The reduced expression of the Cl--extruding cotransporter KCC2 is accompanied by an increase in the Cl--importing cotransporter NKCC1, which together result in excitatory GABA in the hippocampi of HD mice. NKCC1 inhibition by the FDA-approved NKCC1 inhibitor bumetanide abolished the excitatory action of GABA and rescued the performance of R6/2 mice on hippocampal-associated behavioral tests.}, } @article {pmid29382759, year = {2018}, author = {David, L and Li, Y and Ma, J and Garner, E and Zhang, X and Wu, H}, title = {Assembly mechanism of the CARMA1-BCL10-MALT1-TRAF6 signalosome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1499-1504}, pmid = {29382759}, issn = {1091-6490}, support = {DP1 HD087988/HD/NICHD NIH HHS/United States ; R01 AI089882/AI/NIAID NIH HHS/United States ; }, mesh = {B-Cell CLL-Lymphoma 10 Protein/chemistry/genetics/*metabolism ; CARD Signaling Adaptor Proteins/*metabolism ; Cryoelectron Microscopy ; Guanylate Cyclase/*metabolism ; Humans ; Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein/*metabolism ; Multiprotein Complexes ; Mutation ; Polymerization ; Protein Interaction Domains and Motifs ; Signal Transduction ; TNF Receptor-Associated Factor 6/*metabolism ; Time-Lapse Imaging ; }, abstract = {The CARMA1-BCL10-MALT1 (CBM) signalosome is a central mediator of T cell receptor and B cell receptor-induced NF-κB signaling that regulates multiple lymphocyte functions. While caspase-recruitment domain (CARD) membrane-associated guanylate kinase (MAGUK) protein 1 (CARMA1) nucleates B cell lymphoma 10 (BCL10) filament formation through interactions between CARDs, mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) is a paracaspase with structural similarity to caspases, which recruits TNF receptor-associated factor 6 (TRAF6) for K63-linked polyubiquitination. Here we present cryo-electron microscopy (cryo-EM) structure of the BCL10 CARD filament at 4.0-Å resolution. The structure redefines CARD-CARD interactions compared with the previous EM structure determined from a negatively stained sample. Surprisingly, time-lapse confocal imaging shows that BCL10 polymerizes in a unidirectional manner. CARMA1, the BCL10 nucleator, serves as a hub for formation of star-shaped filamentous networks of BCL10 and significantly decreases the lag period of BCL10 polymerization. Cooperative MALT1 interaction with BCL10 filaments observed under EM suggests immediate dimerization of MALT1 in the BCL10 filamentous scaffold. In addition, TRAF6 cooperatively decorates CBM filaments to form higher-order assemblies, likely resulting in all-or-none activation of the downstream pathway. Collectively, these data reveal biophysical mechanisms in the assembly of the CARMA1-BCL10-MALT1-TRAF6 complex for signal transduction.}, } @article {pmid29382758, year = {2018}, author = {Reid, DR and Pashine, N and Wozniak, JM and Jaeger, HM and Liu, AJ and Nagel, SR and de Pablo, JJ}, title = {Auxetic metamaterials from disordered networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1384-E1390}, pmid = {29382758}, issn = {1091-6490}, abstract = {Recent theoretical work suggests that systematic pruning of disordered networks consisting of nodes connected by springs can lead to materials that exhibit a host of unusual mechanical properties. In particular, global properties such as Poisson's ratio or local responses related to deformation can be precisely altered. Tunable mechanical responses would be useful in areas ranging from impact mitigation to robotics and, more generally, for creation of metamaterials with engineered properties. However, experimental attempts to create auxetic materials based on pruning-based theoretical ideas have not been successful. Here we introduce a more realistic model of the networks, which incorporates angle-bending forces and the appropriate experimental boundary conditions. A sequential pruning strategy of select bonds in this model is then devised and implemented that enables engineering of specific mechanical behaviors upon deformation, both in the linear and in the nonlinear regimes. In particular, it is shown that Poisson's ratio can be tuned to arbitrary values. The model and concepts discussed here are validated by preparing physical realizations of the networks designed in this manner, which are produced by laser cutting 2D sheets and are found to behave as predicted. Furthermore, by relying on optimization algorithms, we exploit the networks' susceptibility to tuning to design networks that possess a distribution of stiffer and more compliant bonds and whose auxetic behavior is even greater than that of homogeneous networks. Taken together, the findings reported here serve to establish that pruned networks represent a promising platform for the creation of unique mechanical metamaterials.}, } @article {pmid29382757, year = {2018}, author = {Liu, W and Chen, B and Wang, Y and Meng, C and Huang, H and Huang, XR and Qin, J and Mulay, SR and Anders, HJ and Qiu, A and Yang, B and Freeman, GJ and Lu, HJ and Lin, HY and Zheng, ZH and Lan, HY and Huang, Y and Xia, Y}, title = {RGMb protects against acute kidney injury by inhibiting tubular cell necroptosis via an MLKL-dependent mechanism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1475-E1484}, pmid = {29382757}, issn = {1091-6490}, support = {P50 CA101942/CA/NCI NIH HHS/United States ; }, mesh = {Acute Kidney Injury/etiology/pathology/*prevention & control ; Animals ; *Apoptosis ; Kidney Tubules/metabolism/*pathology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; *Necrosis ; Nerve Tissue Proteins/*physiology ; Protective Agents/pharmacology ; Protein Kinases/genetics/*metabolism ; Reperfusion Injury/*complications ; }, abstract = {Tubular cell necrosis is a key histological feature of acute kidney injury (AKI). Necroptosis is a type of programed necrosis, which is executed by mixed lineage kinase domain-like protein (MLKL) upon its binding to the plasma membrane. Emerging evidence indicates that necroptosis plays a critical role in the development of AKI. However, it is unclear whether renal tubular cells undergo necroptosis in vivo and how the necroptotic pathway is regulated during AKI. Repulsive guidance molecule (RGM)-b is a member of the RGM family. Our previous study demonstrated that RGMb is highly expressed in kidney tubular epithelial cells, but its biological role in the kidney has not been well characterized. In the present study, we found that RGMb reduced membrane-associated MLKL levels and inhibited necroptosis in cultured cells. During ischemia/reperfusion injury (IRI) or oxalate nephropathy, MLKL was induced to express on the apical membrane of proximal tubular (PT) cells. Specific knockout of Rgmb in tubular cells (Rgmb cKO) increased MLKL expression at the apical membrane of PT cells and induced more tubular cell death and more severe renal dysfunction compared with wild-type mice. Treatment with the necroptosis inhibitor Necrostatin-1 or GSK'963 reduced MLKL expression on the apical membrane of PT cells and ameliorated renal function impairment after IRI in both wild-type and Rgmb cKO mice. Taken together, our results suggest that proximal tubular cell necroptosis plays an important role in AKI, and that RGMb protects against AKI by inhibiting MLKL membrane association and necroptosis in proximal tubular cells.}, } @article {pmid29382756, year = {2018}, author = {Tan, Q and Brunetti, L and Rousseaux, MWC and Lu, HC and Wan, YW and Revelli, JP and Liu, Z and Goodell, MA and Zoghbi, HY}, title = {Loss of Capicua alters early T cell development and predisposes mice to T cell lymphoblastic leukemia/lymphoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1511-E1519}, pmid = {29382756}, issn = {1091-6490}, support = {F32 NS083091/NS/NINDS NIH HHS/United States ; U54 HD083092/HD/NICHD NIH HHS/United States ; P30 CA125123/CA/NCI NIH HHS/United States ; P30 AI036211/AI/NIAID NIH HHS/United States ; S10 RR024574/RR/NCRR NIH HHS/United States ; R37 NS027699/NS/NINDS NIH HHS/United States ; R01 NS027699/NS/NINDS NIH HHS/United States ; R01 CA183252/CA/NCI NIH HHS/United States ; R01 DK092883/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; 201210MFE-290072-173743//CIHR/Canada ; }, mesh = {Animals ; *Cell Differentiation ; Cells, Cultured ; *Disease Susceptibility ; Mice ; Mice, Knockout ; Mutation ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*etiology/metabolism/pathology ; Proto-Oncogene Proteins c-myc/genetics/metabolism ; Receptor, Notch1/genetics/metabolism ; Repressor Proteins/*physiology ; Signal Transduction ; T-Lymphocytes/metabolism/*pathology ; ras Proteins/genetics/metabolism ; }, abstract = {Capicua (CIC) regulates a transcriptional network downstream of the RAS/MAPK signaling cascade. In Drosophila, CIC is important for many developmental processes, including embryonic patterning and specification of wing veins. In humans, CIC has been implicated in neurological diseases, including spinocerebellar ataxia type 1 (SCA1) and a neurodevelopmental syndrome. Additionally, we and others have reported mutations in CIC in several cancers. However, whether CIC is a tumor suppressor remains to be formally tested. In this study, we found that deletion of Cic in adult mice causes T cell acute lymphoblastic leukemia/lymphoma (T-ALL). Using hematopoietic-specific deletion and bone marrow transplantation studies, we show that loss of Cic from hematopoietic cells is sufficient to drive T-ALL. Cic-null tumors show up-regulation of the KRAS pathway as well as activation of the NOTCH1 and MYC transcriptional programs. In sum, we demonstrate that loss of CIC causes T-ALL, establishing it as a tumor suppressor for lymphoid malignancies. Moreover, we show that mouse models lacking CIC in the hematopoietic system are robust models for studying the role of RAS signaling as well as NOTCH1 and MYC transcriptional programs in T-ALL.}, } @article {pmid29382755, year = {2018}, author = {Su, YB and Peng, B and Li, H and Cheng, ZX and Zhang, TT and Zhu, JX and Li, D and Li, MY and Ye, JZ and Du, CC and Zhang, S and Zhao, XL and Yang, MJ and Peng, XX}, title = {Pyruvate cycle increases aminoglycoside efficacy and provides respiratory energy in bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1578-E1587}, pmid = {29382755}, issn = {1091-6490}, mesh = {Aminoglycosides/*pharmacology ; Anti-Bacterial Agents/*pharmacology ; Citric Acid Cycle/drug effects ; Edwardsiella tarda/*drug effects/*metabolism ; Energy Metabolism/drug effects ; Escherichia coli/*drug effects/*metabolism ; Phosphoenolpyruvate/metabolism ; Pyruvic Acid/*metabolism ; }, abstract = {The emergence and ongoing spread of multidrug-resistant bacteria puts humans and other species at risk for potentially lethal infections. Thus, novel antibiotics or alternative approaches are needed to target drug-resistant bacteria, and metabolic modulation has been documented to improve antibiotic efficacy, but the relevant metabolic mechanisms require more studies. Here, we show that glutamate potentiates aminoglycoside antibiotics, resulting in improved elimination of antibiotic-resistant pathogens. When exploring the metabolic flux of glutamate, it was found that the enzymes that link the phosphoenolpyruvate (PEP)-pyruvate-AcCoA pathway to the TCA cycle were key players in this increased efficacy. Together, the PEP-pyruvate-AcCoA pathway and TCA cycle can be considered the pyruvate cycle (P cycle). Our results show that inhibition or gene depletion of the enzymes in the P cycle shut down the TCA cycle even in the presence of excess carbon sources, and that the P cycle operates routinely as a general mechanism for energy production and regulation in Escherichia coli and Edwardsiella tarda These findings address metabolic mechanisms of metabolite-induced potentiation and fundamental questions about bacterial biochemistry and energy metabolism.}, } @article {pmid29382754, year = {2018}, author = {Bjerknes, TL and Dagslott, NC and Moser, EI and Moser, MB}, title = {Path integration in place cells of developing rats.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1637-E1646}, pmid = {29382754}, issn = {1091-6490}, mesh = {Animals ; Entorhinal Cortex/growth & development/physiology ; Female ; Hippocampus/cytology/growth & development/physiology ; Male ; Models, Neurological ; Orientation ; Place Cells/*physiology ; Rats/*growth & development/physiology ; Rats, Long-Evans ; Space Perception ; }, abstract = {Place cells in the hippocampus and grid cells in the medial entorhinal cortex rely on self-motion information and path integration for spatially confined firing. Place cells can be observed in young rats as soon as they leave their nest at around 2.5 wk of postnatal life. In contrast, the regularly spaced firing of grid cells develops only after weaning, during the fourth week. In the present study, we sought to determine whether place cells are able to integrate self-motion information before maturation of the grid-cell system. Place cells were recorded on a 200-cm linear track while preweaning, postweaning, and adult rats ran on successive trials from a start wall to a box at the end of a linear track. The position of the start wall was altered in the middle of the trial sequence. When recordings were made in complete darkness, place cells maintained fields at a fixed distance from the start wall regardless of the age of the animal. When lights were on, place fields were determined primarily by external landmarks, except at the very beginning of the track. This shift was observed in both young and adult animals. The results suggest that preweaning rats are able to calculate distances based on information from self-motion before the grid-cell system has matured to its full extent.}, } @article {pmid29382753, year = {2018}, author = {Hoffman, JF}, title = {Evidence that asymmetry of the membrane/cytoskeletal complex in human red blood cell ghosts is responsible for their biconcave shape.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1641-1645}, pmid = {29382753}, issn = {1091-6490}, mesh = {*Cell Shape ; Centrifugation ; Cytoskeleton/ultrastructure ; *Erythrocyte Deformability ; *Erythrocyte Membrane ; Erythrocytes/*cytology ; Humans ; }, abstract = {The main conclusion of the results reported in this article is that during centrifugation, sphered red blood cell ghosts become oriented in their attachment to a coverslip such that a dense band within the ghosts lies parallel to the centrifugal field. The result of the orientation of this dense band is that when the attached spherical ghosts are shrunken to become biconcave discs, they do so by directly collapsing on themselves without any lateral motion. This result is interpreted to suggest that a dense band, relative to the dimple, resides in the rim of the ghost and is responsible for its biconcave shape. These results confirm the conclusions reached in a previous publication in which there was the uncertainty that the shape change of the spherical ghosts to discs could not be directly imaged. The present work corrects this limitation by use of a chamber in which the tonicity of the solutions in the ghosts' surround could be altered by perfusion coupled with constant microscopic imaging. The identity of the components that are responsible for the differences in the density (mass) between the rim and the dimple regions of the cytoskeletal/membrane complex in the biconcave disk are unknown. It is also unknown what forces apply or what the explanation is for the unique orientation of the dense band during the ghosts' centrifugation, as described in this article. Nevertheless, the results reported in this article indicate the membrane's underlying cytoskeletal complex is asymmetrically distributed.}, } @article {pmid29382752, year = {2018}, author = {Wang, M and He, Y and Sejnowski, TJ and Yu, X}, title = {Brain-state dependent astrocytic Ca2+ signals are coupled to both positive and negative BOLD-fMRI signals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1647-E1656}, pmid = {29382752}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Astrocytes/*metabolism ; Brain/*diagnostic imaging/*metabolism ; Brain Mapping ; Calcium/metabolism ; *Calcium Signaling ; Magnetic Resonance Imaging ; Oxygen/*blood ; Rats, Sprague-Dawley ; }, abstract = {Astrocytic Ca2+-mediated gliovascular interactions regulate the neurovascular network in situ and in vivo. However, it is difficult to measure directly both the astrocytic activity and fMRI to relate the various forms of blood-oxygen-level-dependent (BOLD) signaling to brain states under normal and pathological conditions. In this study, fMRI and GCaMP-mediated Ca2+ optical fiber recordings revealed distinct evoked astrocytic Ca2+ signals that were coupled with positive BOLD signals and intrinsic astrocytic Ca2+ signals that were coupled with negative BOLD signals. Both evoked and intrinsic astrocytic calcium signal could occur concurrently or respectively during stimulation. The intrinsic astrocytic calcium signal can be detected globally in multiple cortical sites in contrast to the evoked astrocytic calcium signal only detected at the activated cortical region. Unlike propagating Ca2+ waves in spreading depolarization/depression, the intrinsic Ca2+ spikes occurred simultaneously in both hemispheres and were initiated upon the activation of the central thalamus and midbrain reticular formation. The occurrence of the intrinsic astrocytic calcium signal is strongly coincident with an increased EEG power level of the brain resting-state fluctuation. These results demonstrate highly correlated astrocytic Ca2+ spikes with bidirectional fMRI signals based on the thalamic regulation of cortical states, depicting a brain-state dependency of both astrocytic Ca2+ and BOLD fMRI signals.}, } @article {pmid29382751, year = {2018}, author = {Xiao, Q and Ludwig, AK and Romanò, C and Buzzacchera, I and Sherman, SE and Vetro, M and Vértesy, S and Kaltner, H and Reed, EH and Möller, M and Wilson, CJ and Hammer, DA and Oscarson, S and Klein, ML and Gabius, HJ and Percec, V}, title = {Exploring functional pairing between surface glycoconjugates and human galectins using programmable glycodendrimersomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {11}, pages = {E2509-E2518}, pmid = {29382751}, issn = {1091-6490}, mesh = {Cell Membrane/chemistry/metabolism ; Dendrimers/*chemistry ; Dimerization ; Galectins/*chemistry/metabolism ; Glycoconjugates/chemistry/*metabolism ; Glycomics/*methods ; Humans ; Polysaccharides/chemistry/metabolism ; }, abstract = {Precise translation of glycan-encoded information into cellular activity depends critically on highly specific functional pairing between glycans and their human lectin counter receptors. Sulfoglycolipids, such as sulfatides, are important glycolipid components of the biological membranes found in the nervous and immune systems. The optimal molecular and spatial design aspects of sulfated and nonsulfated glycans with high specificity for lectin-mediated bridging are unknown. To elucidate how different molecular and spatial aspects combine to ensure the high specificity of lectin-mediated bridging, a bottom-up toolbox is devised. To this end, negatively surface-charged glycodendrimersomes (GDSs), of different nanoscale dimensions, containing sulfo-lactose groups are self-assembled in buffer from a synthetic sulfatide mimic: Janus glycodendrimer (JGD) containing a 3'-O-sulfo-lactose headgroup. Also prepared for comparative analysis are GDSs with nonsulfated lactose, a common epitope of human membranes. These self-assembled GDSs are employed in aggregation assays with 15 galectins, comprising disease-related human galectins, and other natural and engineered variants from four families, having homodimeric, heterodimeric, and chimera architectures. There are pronounced differences in aggregation capacity between human homodimeric and heterodimeric galectins, and also with respect to their responsiveness to the charge of carbohydrate-derived ligand. Assays reveal strong differential impact of ligand surface charge and density, as well as lectin concentration and structure, on the extent of surface cross-linking. These findings demonstrate how synthetic JGD-headgroup tailoring teamed with protein engineering and network assays can help explain how molecular matchmaking operates in the cellular context of glycan and lectin complexity.}, } @article {pmid29382750, year = {2018}, author = {El Baggari, I and Savitzky, BH and Admasu, AS and Kim, J and Cheong, SW and Hovden, R and Kourkoutis, LF}, title = {Nature and evolution of incommensurate charge order in manganites visualized with cryogenic scanning transmission electron microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1445-1450}, pmid = {29382750}, issn = {1091-6490}, abstract = {Incommensurate charge order in hole-doped oxides is intertwined with exotic phenomena such as colossal magnetoresistance, high-temperature superconductivity, and electronic nematicity. Here, we map, at atomic resolution, the nature of incommensurate charge-lattice order in a manganite using scanning transmission electron microscopy at room temperature and cryogenic temperature ([Formula: see text]93 K). In diffraction, the ordering wave vector changes upon cooling, a behavior typically associated with incommensurate order. However, using real space measurements, we discover that the ordered state forms lattice-locked regions over a few wavelengths interspersed with phase defects and changing periodicity. The cations undergo picometer-scale ([Formula: see text]6 pm to 11 pm) transverse displacements, suggesting that charge-lattice coupling is strong. We further unearth phase inhomogeneity in the periodic lattice displacements at room temperature, and emergent phase coherence at 93 K. Such local phase variations govern the long-range correlations of the charge-ordered state and locally change the periodicity of the modulations, resulting in wave vector shifts in reciprocal space. These atomically resolved observations underscore the importance of lattice coupling and phase inhomogeneity, and provide a microscopic explanation for putative "incommensurate" order in hole-doped oxides.}, } @article {pmid29382749, year = {2018}, author = {Ross, B and Krapp, S and Augustin, M and Kierfersauer, R and Arciniega, M and Geiss-Friedlander, R and Huber, R}, title = {Structures and mechanism of dipeptidyl peptidases 8 and 9, important players in cellular homeostasis and cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1437-E1445}, pmid = {29382749}, issn = {1091-6490}, mesh = {Binding Sites ; Catalytic Domain ; Crystallography, X-Ray ; Dipeptidases/*chemistry/metabolism ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/*chemistry/metabolism ; Homeostasis/*physiology ; Humans ; Molecular Structure ; *Protein Conformation ; Protein Domains ; }, abstract = {Dipeptidyl peptidases 8 and 9 are intracellular N-terminal dipeptidyl peptidases (preferentially postproline) associated with pathophysiological roles in immune response and cancer biology. While the DPP family member DPP4 is extensively characterized in molecular terms as a validated therapeutic target of type II diabetes, experimental 3D structures and ligand-/substrate-binding modes of DPP8 and DPP9 have not been reported. In this study we describe crystal and molecular structures of human DPP8 (2.5 Å) and DPP9 (3.0 Å) unliganded and complexed with a noncanonical substrate and a small molecule inhibitor, respectively. Similar to DPP4, DPP8 and DPP9 molecules consist of one β-propeller and α/β hydrolase domain, forming a functional homodimer. However, they differ extensively in the ligand binding site structure. In intriguing contrast to DPP4, where liganded and unliganded forms are closely similar, ligand binding to DPP8/9 induces an extensive rearrangement at the active site through a disorder-order transition of a 26-residue loop segment, which partially folds into an α-helix (R-helix), including R160/133, a key residue for substrate binding. As vestiges of this helix are also seen in one of the copies of the unliganded form, conformational selection may contributes to ligand binding. Molecular dynamics simulations support increased flexibility of the R-helix in the unliganded state. Consistently, enzyme kinetics assays reveal a cooperative allosteric mechanism. DPP8 and DPP9 are closely similar and display few opportunities for targeted ligand design. However, extensive differences from DPP4 provide multiple cues for specific inhibitor design and development of the DPP family members as therapeutic targets or antitargets.}, } @article {pmid29382748, year = {2018}, author = {}, title = {Correction for Noh et al., ATRX tolerates activity-dependent histone H3 methyl/phos switching to maintain repetitive element silencing in neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1329}, doi = {10.1073/pnas.1800522115}, pmid = {29382748}, issn = {1091-6490}, } @article {pmid29382747, year = {2018}, author = {Betts, BC and Bastian, D and Iamsawat, S and Nguyen, H and Heinrichs, JL and Wu, Y and Daenthanasanmak, A and Veerapathran, A and O'Mahony, A and Walton, K and Reff, J and Horna, P and Sagatys, EM and Lee, MC and Singer, J and Chang, YJ and Liu, C and Pidala, J and Anasetti, C and Yu, XZ}, title = {Targeting JAK2 reduces GVHD and xenograft rejection through regulation of T cell differentiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1582-1587}, pmid = {29382747}, issn = {1091-6490}, support = {R01 HL133823/HL/NHLBI NIH HHS/United States ; R01 CA143812/CA/NCI NIH HHS/United States ; R01 CA169116/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; K08 HL116547/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Cell Differentiation ; Female ; Graft vs Host Disease/genetics/*immunology/prevention & control ; Graft vs Leukemia Effect/genetics/*immunology ; Janus Kinase 2/*physiology ; Lymphocyte Activation ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Primary Myelofibrosis/genetics/*immunology/prevention & control ; Skin Transplantation ; T-Lymphocytes/*immunology ; Th2 Cells/*immunology ; Xenograft Model Antitumor Assays ; }, abstract = {Janus kinase 2 (JAK2) signal transduction is a critical mediator of the immune response. JAK2 is implicated in the onset of graft-versus-host disease (GVHD), which is a significant cause of transplant-related mortality after allogeneic hematopoietic cell transplantation (allo-HCT). Transfer of JAK2-/- donor T cells to allogeneic recipients leads to attenuated GVHD yet maintains graft-versus-leukemia. Th1 differentiation among JAK2-/- T cells is significantly decreased compared with wild-type controls. Conversely, iTreg and Th2 polarization is significantly increased among JAK2-/- T cells. Pacritinib is a multikinase inhibitor with potent activity against JAK2. Pacritinib significantly reduces GVHD and xenogeneic skin graft rejection in distinct rodent models and maintains donor antitumor immunity. Moreover, pacritinib spares iTregs and polarizes Th2 responses as observed among JAK2-/- T cells. Collectively, these data clearly identify JAK2 as a therapeutic target to control donor alloreactivity and promote iTreg responses after allo-HCT or solid organ transplantation. As such, a phase I/II acute GVHD prevention trial combining pacritinib with standard immune suppression after allo-HCT is actively being investigated (https://clinicaltrials.gov/ct2/show/NCT02891603).}, } @article {pmid29382746, year = {2018}, author = {Kim, Y and Terng, EL and Riekhof, WR and Cahoon, EB and Cerutti, H}, title = {Endoplasmic reticulum acyltransferase with prokaryotic substrate preference contributes to triacylglycerol assembly in Chlamydomonas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1652-1657}, pmid = {29382746}, issn = {1091-6490}, mesh = {Acyltransferases/*metabolism ; Algal Proteins/*metabolism ; Chlamydomonas reinhardtii/growth & development/*metabolism ; Chloroplasts/*metabolism ; Endoplasmic Reticulum/*metabolism ; Phylogeny ; Substrate Specificity ; Triglycerides/*metabolism ; }, abstract = {Understanding the unique features of triacylglycerol (TAG) metabolism in microalgae may be necessary to realize the full potential of these organisms for biofuel and biomaterial production. In the unicellular green alga Chlamydomonas reinhardtii a chloroplastic (prokaryotic) pathway has been proposed to play a major role in TAG precursor biosynthesis. However, as reported here, C. reinhardtii contains a chlorophyte-specific lysophosphatidic acid acyltransferase, CrLPAAT2, that localizes to endoplasmic reticulum (ER) membranes. Unlike canonical, ER-located LPAATs, CrLPAAT2 prefers palmitoyl-CoA over oleoyl-CoA as the acyl donor substrate. RNA-mediated suppression of CrLPAAT2 indicated that the enzyme is required for TAG accumulation under nitrogen deprivation. Our findings suggest that Chlamydomonas has a distinct glycerolipid assembly pathway that relies on CrLPAAT2 to generate prokaryotic-like TAG precursors in the ER.}, } @article {pmid29382745, year = {2018}, author = {Dietze, MC and Fox, A and Beck-Johnson, LM and Betancourt, JL and Hooten, MB and Jarnevich, CS and Keitt, TH and Kenney, MA and Laney, CM and Larsen, LG and Loescher, HW and Lunch, CK and Pijanowski, BC and Randerson, JT and Read, EK and Tredennick, AT and Vargas, R and Weathers, KC and White, EP}, title = {Iterative near-term ecological forecasting: Needs, opportunities, and challenges.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1424-1432}, pmid = {29382745}, issn = {1091-6490}, mesh = {Bayes Theorem ; Climate Change ; Ecology/*education/*methods/trends ; Ecosystem ; Forecasting ; Humans ; Models, Theoretical ; }, abstract = {Two foundational questions about sustainability are "How are ecosystems and the services they provide going to change in the future?" and "How do human decisions affect these trajectories?" Answering these questions requires an ability to forecast ecological processes. Unfortunately, most ecological forecasts focus on centennial-scale climate responses, therefore neither meeting the needs of near-term (daily to decadal) environmental decision-making nor allowing comparison of specific, quantitative predictions to new observational data, one of the strongest tests of scientific theory. Near-term forecasts provide the opportunity to iteratively cycle between performing analyses and updating predictions in light of new evidence. This iterative process of gaining feedback, building experience, and correcting models and methods is critical for improving forecasts. Iterative, near-term forecasting will accelerate ecological research, make it more relevant to society, and inform sustainable decision-making under high uncertainty and adaptive management. Here, we identify the immediate scientific and societal needs, opportunities, and challenges for iterative near-term ecological forecasting. Over the past decade, data volume, variety, and accessibility have greatly increased, but challenges remain in interoperability, latency, and uncertainty quantification. Similarly, ecologists have made considerable advances in applying computational, informatic, and statistical methods, but opportunities exist for improving forecast-specific theory, methods, and cyberinfrastructure. Effective forecasting will also require changes in scientific training, culture, and institutions. The need to start forecasting is now; the time for making ecology more predictive is here, and learning by doing is the fastest route to drive the science forward.}, } @article {pmid29382744, year = {2018}, author = {Dixon, ML and De La Vega, A and Mills, C and Andrews-Hanna, J and Spreng, RN and Cole, MW and Christoff, K}, title = {Heterogeneity within the frontoparietal control network and its relationship to the default and dorsal attention networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1598-E1607}, pmid = {29382744}, issn = {1091-6490}, mesh = {Adult ; Attention ; Brain Mapping ; *Executive Function ; Female ; Frontal Lobe/chemistry/*physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Neural Networks (Computer) ; Young Adult ; }, abstract = {The frontoparietal control network (FPCN) plays a central role in executive control. It has been predominantly viewed as a unitary domain general system. Here, we examined patterns of FPCN functional connectivity (FC) across multiple conditions of varying cognitive demands, to test for FPCN heterogeneity. We identified two distinct subsystems within the FPCN based on hierarchical clustering and machine learning classification analyses of within-FPCN FC patterns. These two FPCN subsystems exhibited distinct patterns of FC with the default network (DN) and the dorsal attention network (DAN). FPCNA exhibited stronger connectivity with the DN than the DAN, whereas FPCNB exhibited the opposite pattern. This twofold FPCN differentiation was observed across four independent datasets, across nine different conditions (rest and eight tasks), at the level of individual-participant data, as well as in meta-analytic coactivation patterns. Notably, the extent of FPCN differentiation varied across conditions, suggesting flexible adaptation to task demands. Finally, we used meta-analytic tools to identify several functional domains associated with the DN and DAN that differentially predict activation in the FPCN subsystems. These findings reveal a flexible and heterogeneous FPCN organization that may in part emerge from separable DN and DAN processing streams. We propose that FPCNA may be preferentially involved in the regulation of introspective processes, whereas FPCNB may be preferentially involved in the regulation of visuospatial perceptual attention.}, } @article {pmid29382743, year = {2018}, author = {}, title = {Correction for Ferrari et al., Hypoxia treatment reverses neurodegenerative disease in a mouse model of Leigh syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1330}, doi = {10.1073/pnas.1800151115}, pmid = {29382743}, issn = {1091-6490}, } @article {pmid29382396, year = {2018}, author = {Aziz, SA and Nelwan, EJ and Sukrisman, L and Suhendro, S}, title = {Higher cut-off serum procalcitonin level for sepsis diagnosis in metastatic solid tumor patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {84}, pmid = {29382396}, issn = {1756-0500}, mesh = {Adult ; Calcitonin/*blood/standards ; Cross-Sectional Studies ; Female ; Humans ; Male ; Middle Aged ; Neoplasm Metastasis ; Neoplasms/*complications/pathology ; Prognosis ; ROC Curve ; Reference Values ; Sepsis/*blood/complications/diagnosis ; Systemic Inflammatory Response Syndrome/*blood/complications/diagnosis ; }, abstract = {OBJECTIVE: The current study aimed to know procalcitonin levels in patients with metastatic tumor, and to discover the cut-off point for sepsis in this population. A cross-sectional study was conducted with patients with solid tumor. Sepsis and systemic inflammation response syndrome (SIRS) were identified using clinical, laboratory, and microbiological criteria. The cut-off point was determined using receiver operating characteristic (ROC) curve.

RESULTS: A total of 112 subjects enrolled in this study, 51% male, mean age 47.9 ± 12.47 years. Among 71 (63.4%) patients who had metastasis, 36 (32.1%) had sepsis and 6 (5.3%) experienced SIRS. In the absence of sepsis, the procalcitonin levels were significantly higher in patients with metastatic tumor compared to those without [0.25 ng/mL (0.07-1.76) vs. 0.09 ng/mL (0.03-0.54); p < 0.001]. The ROC curve showed that levels of procalcitonin for sepsis in metastatic solid tumors were in the area under curve (AUC) [0.956; CI 0.916-0.996]. Cut-off point of procalcitonin for sepsis was 1.14 ng/mL, Sn 86%, and Sp 88%. Thus, the results show that metastatic tumor affects the patients' procalcitonin level, even in the absence of sepsis. The cut-off point of procalcitonin level for diagnosing sepsis in the meta-static solid tumor was higher compared to the standard value.}, } @article {pmid29382384, year = {2018}, author = {Wang, Z and Potoyan, DA and Wolynes, PG}, title = {Modeling the therapeutic efficacy of NFκB synthetic decoy oligodeoxynucleotides (ODNs).}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {4}, pmid = {29382384}, issn = {1752-0509}, support = {P01 GM071862/GM/NIGMS NIH HHS/United States ; P01 GM071862//PPG Grant/ ; }, abstract = {BACKGROUND: Transfection of NF κB synthetic decoy Oligodeoxynucleotides (ODNs) has been proposed as a promising therapeutic strategy for a variety of diseases arising from constitutive activation of the eukaryotic transcription factor NF κB. The decoy approach faces some limitations under physiological conditions notably nuclease-induced degradation.

RESULTS: In this work, we show how a systems pharmacology model of NF κB regulatory networks displaying oscillatory temporal dynamics, can be used to predict quantitatively the dependence of therapeutic efficacy of NF κB synthetic decoy ODNs on dose, unbinding kinetic rates and nuclease-induced degradation rates. Both deterministic mass action simulations and stochastic simulations of the systems biology model show that the therapeutic efficacy of synthetic decoy ODNs is inversely correlated with unbinding kinetic rates, nuclease-induced degradation rates and molecular stripping rates, but is positively correlated with dose. We show that the temporal coherence of the stochastic dynamics of NF κB regulatory networks is most sensitive to adding NF κB synthetic decoy ODNs having unbinding time-scales that are in-resonance with the time-scale of the limit cycle of the network.

CONCLUSIONS: The pharmacokinetics/pharmacodynamics (PK/PD) predicted by the systems-level model should provide quantitative guidance for in-depth translational research of optimizing the thermodynamics/kinetic properties of synthetic decoy ODNs.}, } @article {pmid29382378, year = {2018}, author = {Maestre, JP and Jennings, W and Wylie, D and Horner, SD and Siegel, J and Kinney, KA}, title = {Filter forensics: microbiota recovery from residential HVAC filters.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {22}, pmid = {29382378}, issn = {2049-2618}, support = {TXHHU0023-13//U.S. Department of Housing and Urban Development/International ; }, mesh = {Air Conditioning ; *Air Microbiology ; Air Pollution, Indoor/analysis ; Bacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Fungal/genetics ; Dust/*analysis ; Fungi/*classification/genetics/isolation & purification ; Heating ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Microbiota ; Sequence Analysis, DNA/*methods ; Ventilation ; }, abstract = {BACKGROUND: Establishing reliable methods for assessing the microbiome within the built environment is critical for understanding the impact of biological exposures on human health. High-throughput DNA sequencing of dust samples provides valuable insights into the microbiome present in human-occupied spaces. However, the effect that different sampling methods have on the microbial community recovered from dust samples is not well understood across sample types. Heating, ventilation, and air conditioning (HVAC) filters hold promise as long-term, spatially integrated, high volume samplers to characterize the airborne microbiome in homes and other climate-controlled spaces. In this study, the effect that dust recovery method (i.e., cut and elution, swabbing, or vacuuming) has on the microbial community structure, membership, and repeatability inferred by Illumina sequencing was evaluated.

RESULTS: The results indicate that vacuum samples captured higher quantities of total, bacterial, and fungal DNA than swab or cut samples. Repeated swab and vacuum samples collected from the same filter were less variable than cut samples with respect to both quantitative DNA recovery and bacterial community structure. Vacuum samples captured substantially greater bacterial diversity than the other methods, whereas fungal diversity was similar across all three methods. Vacuum and swab samples of HVAC filter dust were repeatable and generally superior to cut samples. Nevertheless, the contribution of environmental and human sources to the bacterial and fungal communities recovered via each sampling method was generally consistent across the methods investigated.

CONCLUSIONS: Dust recovery methodologies have been shown to affect the recovery, repeatability, structure, and membership of microbial communities recovered from dust samples in the built environment. The results of this study are directly applicable to indoor microbiota studies utilizing the filter forensics approach. More broadly, this study provides a better understanding of the microbial community variability attributable to sampling methodology and helps inform interpretation of data collected from other types of dust samples collected from indoor environments.}, } @article {pmid29382377, year = {2018}, author = {Hazmiri, FE and Nachite, F and Skandour, D and Raji, A and El Ganouni, NCI and Rais, H}, title = {Lateral cervical thymic cyst in a child: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {85}, pmid = {29382377}, issn = {1756-0500}, mesh = {Child ; Diagnosis, Differential ; Humans ; Male ; Mediastinal Cyst/*diagnosis/diagnostic imaging ; *Neck ; Tomography, X-Ray Computed ; }, abstract = {BACKGROUND: Cervical thymic cysts are uncommon lesions, rarely considered in the differential diagnosis of neck cysts in children.

CASE PRESENTATION: We report a rare case of multiloculated thymic cyst in an 8-year-old boy on the right side of the neck. Perioperative diagnosis was a cystic hygroma. Macroscopic examination showed a cystic mass measuring 6.5 cm in total length. Histopathology of the excised specimen revealed thymic tissue with prominent Hassall's corpuscles associated with multiloculated cyst. The cyst wall is bordered by a flattened or multilayered epithelium, often abraded.

CONCLUSION: This case is presented here for its rarity and should be included in the differential diagnosis of neck masses in children. So, it's a lesion to be well aware of, particularly by pathologists.}, } @article {pmid29382372, year = {2018}, author = {Negero, MG and Mitike, YB and Worku, AG and Abota, TL}, title = {Skilled delivery service utilization and its association with the establishment of Women's Health Development Army in Yeky district, South West Ethiopia: a multilevel analysis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {83}, pmid = {29382372}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Cross-Sectional Studies ; Delivery, Obstetric/*statistics & numerical data ; Ethiopia ; Female ; Health Facilities/statistics & numerical data ; Humans ; Logistic Models ; Maternal Health Services/*statistics & numerical data ; Multilevel Analysis ; Multivariate Analysis ; Pregnancy ; Prenatal Care/*statistics & numerical data ; Rural Population/statistics & numerical data ; Urban Population/statistics & numerical data ; Women's Health/*statistics & numerical data ; Young Adult ; }, abstract = {BACKGROUND: Because of the unacceptably high maternal and perinatal morbidity and mortality, the government of Ethiopia has established health extension program with a community-based network involving health extension workers (HEWs) and a community level women organization which is known as "Women's Health Development Army" (WHDA). Currently, the HEWs and WHDA network is the approach preferred by the government to register pregnant women and encourage them to link in the healthcare system. However, its association with skilled delivery service utilization is not well known.

METHODS: A community-based cross-sectional study was conducted from January to February 2015. Within 380 clusters of WHDA, a total of 748 reproductive-age women who gave birth in 1 year preceding the study, were included using multistage sampling technique. The data were entered into EPI info version 7 statistical software and exported to STATA version 11 for analysis. Multilevel analysis technique was applied to check for an association of selected variables with a utilization of skilled delivery service.

RESULTS: About 45% of women have received skilled delivery care. A significant heterogeneity was observed between "Women's Health Development Teams (clusters)" for skilled delivery care service utilization which explains about 62% of the total variation. Individual-level predictors including urban residence [AOR (95% CI) 35.10 (4.62, 266.52)], previous exposure of complications [AOR (95% CI) 3.81 (1.60, 9.08)], at least four ANC visits [AOR (95% CI) 7.44 (1.48, 37.42)] and preference of skilled personnel [AOR (95% CI) 8.11 (2.61, 25.15)] were significantly associated with skilled delivery service use. Among cluster level variables, the distance of clusters within 2 km radius from the nearest health facility was significantly associated [AOR (95% CI) 6.03 (1.92, 18.93)] with skilled delivery service utilization.

CONCLUSIONS: In this study, significant variation among clusters of WHDA was observed. Both individual and cluster level variables were identified to predict skilled delivery service utilization. Encouraging women to have frequent ANC visits (- 4 and above), enhancing awareness creation towards the delivery care attendance, constructing more health facilities and roads in hard to reach areas and establishing telemedicine services are recommended.}, } @article {pmid29382341, year = {2018}, author = {Meiselman, MR and Kingan, TG and Adams, ME}, title = {Stress-induced reproductive arrest in Drosophila occurs through ETH deficiency-mediated suppression of oogenesis and ovulation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {18}, pmid = {29382341}, issn = {1741-7007}, support = {R01 GM067310/GM/NIGMS NIH HHS/United States ; GM06713/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Environmental stressors induce changes in endocrine state, leading to energy re-allocation from reproduction to survival. Female Drosophila melanogaster respond to thermal and nutrient stressors by arresting egg production through elevation of the steroid hormone ecdysone. However, the mechanisms through which this reproductive arrest occurs are not well understood.

RESULTS: Here we report that stress-induced elevation of ecdysone is accompanied by decreased levels of ecdysis triggering hormone (ETH). Depressed levels of circulating ETH lead to attenuated activity of its targets, including juvenile hormone-producing corpus allatum and, as we describe here for the first time, octopaminergic neurons of the oviduct. Elevation of steroid thereby results in arrested oogenesis, reduced octopaminergic input to the reproductive tract, and consequent suppression of ovulation. ETH mitigates heat or nutritional stress-induced attenuation of fecundity, which suggests that its deficiency is critical to reproductive adaptability.

CONCLUSIONS: Our findings indicate that, as a dual regulator of octopamine and juvenile hormone release, ETH provides a link between stress-induced elevation of ecdysone levels and consequent reduction in fecundity.}, } @article {pmid29382333, year = {2018}, author = {Arnold, ML and Melentijevic, I and Smart, AJ and Driscoll, M}, title = {Q&A: Trash talk: disposal and remote degradation of neuronal garbage.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {17}, pmid = {29382333}, issn = {1741-7007}, support = {F31 GM125307/GM/NIGMS NIH HHS/United States ; F31 NS101969/NS/NINDS NIH HHS/United States ; R01 AG047101/AG/NIA NIH HHS/United States ; R37 AG056510/AG/NIA NIH HHS/United States ; }, abstract = {Caenorhabditis elegans neurons have recently been found to throw out cellular debris for remote degradation and/or storage, adding an "extracellular garbage elimination" option to known intracellular protein and organelle degradation pathways. This Q&A describes initial insights into the biology of seemingly selective protein and organelle elimination by challenged neurons, highlighting mysteries of how garbage is distinguished and sorted in the sending neuron, how the garbage-filled "exophers" appear to elicit degradative responses as they transit neighboring tissue, and how non-digestible materials get thrown out of cells again via processes that may be highly relevant to human neurodegenerative disease mechanisms.}, } @article {pmid29382321, year = {2018}, author = {Liu, D and Hunt, M and Tsai, IJ}, title = {Inferring synteny between genome assemblies: a systematic evaluation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {26}, pmid = {29382321}, issn = {1471-2105}, mesh = {Algorithms ; Animals ; Caenorhabditis elegans/genetics ; *Genome ; Genomics/*methods ; Nematoda/genetics ; }, abstract = {BACKGROUND: Genome assemblies across all domains of life are being produced routinely. Initial analysis of a new genome usually includes annotation and comparative genomics. Synteny provides a framework in which conservation of homologous genes and gene order is identified between genomes of different species. The availability of human and mouse genomes paved the way for algorithm development in large-scale synteny mapping, which eventually became an integral part of comparative genomics. Synteny analysis is regularly performed on assembled sequences that are fragmented, neglecting the fact that most methods were developed using complete genomes. It is unknown to what extent draft assemblies lead to errors in such analysis.

RESULTS: We fragmented genome assemblies of model nematodes to various extents and conducted synteny identification and downstream analysis. We first show that synteny between species can be underestimated up to 40% and find disagreements between popular tools that infer synteny blocks. This inconsistency and further demonstration of erroneous gene ontology enrichment tests raise questions about the robustness of previous synteny analysis when gold standard genome sequences remain limited. In addition, assembly scaffolding using a reference guided approach with a closely related species may result in chimeric scaffolds with inflated assembly metrics if a true evolutionary relationship was overlooked. Annotation quality, however, has minimal effect on synteny if the assembled genome is highly contiguous.

CONCLUSIONS: Our results show that a minimum N50 of 1 Mb is required for robust downstream synteny analysis, which emphasizes the importance of gold standard genomes to the science community, and should be achieved given the current progress in sequencing technology.}, } @article {pmid29382320, year = {2018}, author = {Rueda, AJV and Monzon, AM and Ardanaz, SM and Iglesias, LE and Parisi, G}, title = {Large scale analysis of protein conformational transitions from aqueous to non-aqueous media.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {27}, pmid = {29382320}, issn = {1471-2105}, support = {1402/15//Universidad Nacional de Quilmes/International ; PICT 2013-0232//Agencia Nacional de Promoción Científica y Tecnológica/International ; }, mesh = {Biocatalysis ; Computational Biology/*methods ; Databases, Protein ; Humans ; Protein Structure, Secondary ; Protein Structure, Tertiary ; Proteins/*chemistry/metabolism ; Solvents/*chemistry ; Water/*chemistry ; ras Proteins/chemistry/metabolism ; }, abstract = {BACKGROUND: Biocatalysis in organic solvents is nowadays a common practice with a large potential in Biotechnology. Several studies report that proteins which are co-crystallized or soaked in organic solvents preserve their fold integrity showing almost identical arrangements when compared to their aqueous forms. However, it is well established that the catalytic activity of proteins in organic solvents is much lower than in water. In order to explain this diminished activity and to further characterize the behaviour of proteins in non-aqueous environments, we performed a large-scale analysis (1737 proteins) of the conformational diversity of proteins crystallized in aqueous and co-crystallized or soaked in non-aqueous media.

RESULTS: Using proteins' experimentally determined conformational diversity taken from CoDNaS database, we found that proteins in non-aqueous media display much lower conformational diversity when compared to the corresponding conformers obtained in water. When conformational diversity is compared between conformers obtained in different non-aqueous media, their structural differences are larger and mostly independent of the presence of cognate ligands. We also found that conformers corresponding to non-aqueous media have larger but less flexible cavities, lower number of disordered regions and lower active-site residue mobility.

CONCLUSIONS: Our results show that non-aqueous media conformers have specific structural features and that they do not adopt extreme conformations found in aqueous media. This makes them clearly different from their corresponding aqueous conformers.}, } @article {pmid29382313, year = {2018}, author = {Lichtenstein, L and Grübel, K and Spaethe, J}, title = {Opsin expression patterns coincide with photoreceptor development during pupal development in the honey bee, Apis mellifera.}, journal = {BMC developmental biology}, volume = {18}, number = {1}, pages = {1}, pmid = {29382313}, issn = {1471-213X}, support = {SFB1047//Deutsche Forschungsgemeinschaft/International ; }, abstract = {BACKGROUND: The compound eyes of insects allow them to catch photons and convert the energy into electric signals. All compound eyes consist of numerous ommatidia, each comprising a fixed number of photoreceptors. Different ommatidial types are characterized by a specific set of photoreceptors differing in spectral sensitivity. In honey bees, males and females possess different ommatidial types forming distinct retinal mosaics. However, data are lacking on retinal ontogeny and the mechanisms by which the eyes are patterned. In this study, we investigated the intrinsic temporal and circadian expression patterns of the opsins that give rise to the ultraviolet, blue and green sensitive photoreceptors, as well as the morphological maturation of the retina during pupal development of honey bees.

RESULTS: qPCR and histological labeling revealed that temporal opsin mRNA expression differs between sexes and correlates with rhabdom elongation during photoreceptor development. In the first half of the pupal stage, when the rhabdoms of the photoreceptors are still short, worker and (dorsal) drone retinae exhibit similar expression patterns with relatively high levels of UV (UVop) and only marginal levels of blue (BLop) and green (Lop1) opsin mRNA. In the second half of pupation, when photoreceptors and rhabdoms elongate, opsin expression in workers becomes dominated by Lop1 mRNA. In contrast, the dorsal drone eye shows high expression levels of UVop and BLop mRNA, whereas Lop1 mRNA level decreases. Interestingly, opsin expression levels increase up to 22-fold during early adult life. We also found evidence that opsin expression in adult bees is under the control of the endogenous clock.

CONCLUSIONS: Our data indicate that the formation of the sex-specific retinal composition of photoreceptors takes place during the second half of the pupal development, and that opsin mRNA expression levels continue to increase in young bees, which stands in contrast to Drosophila, where the highest expression levels are found during the late pupal stage and remain constant in adults. From an evolutionary perspective, we hypothesize that the delayed retinal maturation during the early adult phase is linked to the delayed transition from indoor to outdoor activities in bees, when vision becomes important.}, } @article {pmid29382299, year = {2018}, author = {Nguyen, NH and Premachandra, HKA and Kilian, A and Knibb, W}, title = {Genomic prediction using DArT-Seq technology for yellowtail kingfish Seriola lalandi.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {107}, pmid = {29382299}, issn = {1471-2164}, support = {Project No. 2013/700//The Australian Seafood CRC/International ; }, mesh = {Animals ; Body Weight/genetics ; Fishes/*genetics/growth & development ; *Genomics ; Genotyping Techniques ; Phenotype ; }, abstract = {BACKGROUND: Genomic prediction using Diversity Arrays Technology (DArT) genotype by sequencing platform has not been reported in yellowtail kingfish (Seriola lalandi). The principal aim of this study was to address this knowledge gap and to assess predictive ability of genomic Best Linear Unbiased Prediction (gBLUP) for traits of commercial importance in a yellowtail kingfish population comprising 752 individuals that had DNA sequence and phenotypic records for growth traits (body weight, fork length and condition index). The gBLUP method was used due to its computational efficiency and it showed similar predictive performance to other approaches, especially for traits whose variation is of polygenic nature, such as body traits analysed in this study. The accuracy or predictive ability of the gBLUP model was estimated for three growth traits: body weight, folk length and condition index.

RESULTS: The prediction accuracy was moderate to high (0.44 to 0.69) for growth-related traits. The predictive ability for body weight increased by 17.0% (from 0.69 to 0.83) when missing genotype was imputed. Within population prediction using five-fold across validation approach showed that the gBLUP model performed well for growth traits (weight, length and condition factor), with the coefficient of determination (R2) from linear regression analysis ranging from 0.49 to 0.71.

CONCLUSIONS: Collectively our results demonstrated, for the first time in yellowtail kingfish, the potential application of genomic selection for growth-related traits in the future breeding program for this species, S. lalandi.}, } @article {pmid29380879, year = {2018}, author = {Badyaev, AV and Morrison, ES}, title = {Emergent buffering balances evolvability and robustness in the evolution of phenotypic flexibility.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {647-662}, doi = {10.1111/evo.13441}, pmid = {29380879}, issn = {1558-5646}, abstract = {Evolution of adaptive phenotypic flexibility requires a system that can dynamically restore and update a functional phenotype in response to environmental change. The architecture of such a system evolves under the conflicting demands of versatility and robustness, and resolution of these demands should be particularly evident in organisms that require external inputs for reiterative trait production within a generation, such as in metabolic networks that underlie yearly acquisition of diet-dependent coloration in birds. Here, we show that a key structural feature of carotenoid networks-redundancy of biochemical pathways-enables these networks to translate variable environmental inputs into consistent phenotypic outcomes. We closely followed life-long changes in structure and utilization of metabolic networks in a large cohort of free-living birds and found that greater individual experience with dietary change between molts leads to wider occupancy of the metabolic network and progressive accumulation of redundant pathways in a functionally active network. This generated a regime of emergent buffering whereby greater dietary experience was mechanistically linked to greater robustness of resulting traits and an increasing ability to retain and implement previous adaptive solutions. Thus, experience-related buffering links evolvability and robustness in carotenoid-metabolizing networks and we argue that this mechanistic principle facilitates the evolution of phenotypic flexibility.}, } @article {pmid29380455, year = {2018}, author = {Bonnet, T and Postma, E}, title = {Fluctuating selection and its (elusive) evolutionary consequences in a wild rodent population.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {572-586}, doi = {10.1111/jeb.13246}, pmid = {29380455}, issn = {1420-9101}, abstract = {Temporal fluctuations in the strength and direction of selection are often proposed as a mechanism that slows down evolution, both over geological and contemporary timescales. Both the prevalence of fluctuating selection and its relevance for evolutionary dynamics remain poorly understood however, especially on contemporary timescales: unbiased empirical estimates of variation in selection are scarce, and the question of how much of the variation in selection translates into variation in genetic change has largely been ignored. Using long-term individual-based data for a wild rodent population, we quantify the magnitude of fluctuating selection on body size. Subsequently, we estimate the evolutionary dynamics of size and test for a link between fluctuating selection and evolution. We show that, over the past 11 years, phenotypic selection on body size has fluctuated significantly. However, the strength and direction of genetic change have remained largely constant over the study period; that is, the rate of genetic change was similar in years where selection favoured heavier vs. lighter individuals. This result suggests that over shorter timescales, fluctuating selection does not necessarily translate into fluctuating evolution. Importantly however, individual-based simulations show that the correlation between fluctuating selection and fluctuating evolution can be obscured by the effect of drift, and that substantially more data are required for a precise and accurate estimate of this correlation. We identify new challenges in measuring the coupling between selection and evolution, and provide methods and guidelines to overcome them.}, } @article {pmid29380454, year = {2018}, author = {Butler, IA and Peters, MK and Kronauer, DJC}, title = {Low levels of hybridization in two species of African driver ants.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {556-571}, doi = {10.1111/jeb.13245}, pmid = {29380454}, issn = {1420-9101}, abstract = {Hybridization in ants can have consequences different from those observed in most other species, with many of the potential deleterious effects being mitigated due to haplodiploidy and eusociality. In some species where colonies are either headed by multiple queens or single queens that mate with many males, hybridization is associated with genetic caste determination, where hybrids develop into workers and purebred individuals develop into queens. A previous study suggested that hybridization occurs between two Dorylus army ant species with multiply mated queens. However, the extent and exact pattern of hybridization have remained unclear, and its possible effect on caste determination has not been investigated. In this study, we aimed to determine the extent and direction of hybridization by measuring how frequently hybrids occur in colonies of both species, and to investigate the possibility of genetic caste determination. We show that hybridization is bidirectional and occurs at equal rates in both species. Hybrid workers make up only 1-2% of the population, and successful interspecific matings represent approximately 2% of all matings in both species. This shows that, although interspecific matings that give rise to worker offspring occur regularly, they are much rarer than intraspecific mating. Finally, we find no evidence of an association between hybridization and genetic caste determination in this population. This means that genetic caste determination is not a necessary outcome of hybridization in ants, even in species where queens mate with multiple males.}, } @article {pmid29380361, year = {2018}, author = {Shapiro, JW and Turner, PE}, title = {Evolution of mutualism from parasitism in experimental virus populations.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {707-712}, doi = {10.1111/evo.13440}, pmid = {29380361}, issn = {1558-5646}, abstract = {While theory suggests conditions under which mutualism may evolve from parasitism, few studies have observed this transition empirically. Previously, we evolved Escherichia coli and the filamentous bacteriophage M13 in 96-well microplates, an environment in which the ancestral phage increased the growth rate and yield of the ancestral bacteria. In the majority of populations, mutualism was maintained or even enhanced between phages and coevolving bacteria; however, these same phages evolved traits that harmed the ancestral E. coli genotype. Here, we set out to determine if mutualism could evolve from this new parasitic interaction. To do so, we chose six evolved phage populations from the original experiment and used them to establish new infections of the ancestral bacteria. After 20 passages, mutualism evolved in almost all replicates, with the remainder growing commensally. Many phage populations also evolved to benefit both their local, evolving bacteria and the ancestral bacteria, though these phages were less beneficial to their co-occurring hosts than phages that harm the ancestral bacteria. These results demonstrate the rapid recovery of mutualism from parasitism, and we discuss how our findings relate to the evolution of phages that enhance the virulence of bacterial pathogens.}, } @article {pmid29380354, year = {2018}, author = {Dodsworth, S and Orejuela, A and Pérez-Escobar, OA and Särkinen, T and Knapp, S}, title = {Digest: Shape-shifting in Solanaceae flowers: The influence of pollinators.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {717-718}, doi = {10.1111/evo.13437}, pmid = {29380354}, issn = {1558-5646}, } @article {pmid29380351, year = {2018}, author = {Clark, CJ and McGuire, JA and Bonaccorso, E and Berv, JS and Prum, RO}, title = {Complex coevolution of wing, tail, and vocal sounds of courting male bee hummingbirds.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {630-646}, doi = {10.1111/evo.13432}, pmid = {29380351}, issn = {1558-5646}, abstract = {Phenotypic characters with a complex physical basis may have a correspondingly complex evolutionary history. Males in the "bee" hummingbird clade court females with sound from tail-feathers, which flutter during display dives. On a phylogeny of 35 species, flutter sound frequency evolves as a gradual, continuous character on most branches. But on at least six internal branches fall two types of major, saltational changes: mode of flutter changes, or the feather that is the sound source changes, causing frequency to jump from one discrete value to another. In addition to their tail "instruments," males also court females with sound from their syrinx and wing feathers, and may transfer or switch instruments over evolutionary time. In support of this, we found a negative phylogenetic correlation between presence of wing trills and singing. We hypothesize this transference occurs because wing trills and vocal songs serve similar functions and are thus redundant. There are also three independent origins of self-convergence of multiple signals, in which the same species produces both a vocal (sung) frequency sweep, and a highly similar nonvocal sound. Moreover, production of vocal, learned song has been lost repeatedly. Male bee hummingbirds court females with a diverse, coevolving array of acoustic traits.}, } @article {pmid29380347, year = {2018}, author = {Martín-Peciña, M and Osuna-Mascaró, C}, title = {Digest: The Red Queen hypothesis demonstrated by the Daphnia-Caullerya host-parasite system†.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {715-716}, doi = {10.1111/evo.13439}, pmid = {29380347}, issn = {1558-5646}, } @article {pmid29380344, year = {2018}, author = {Vincent, AM}, title = {Digest: Sexual selection and conflict in a novel environment.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {713-714}, doi = {10.1111/evo.13438}, pmid = {29380344}, issn = {1558-5646}, } @article {pmid29380042, year = {2018}, author = {Mahendran, R and Thandeeswaran, M and Kiran, G and Arulkumar, M and Ayub Nawaz, KA and Jabastin, J and Janani, B and Anto Thomas, T and Angayarkanni, J}, title = {Evaluation of Pterin, a Promising Drug Candidate from Cyanide Degrading Bacteria.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {684-693}, pmid = {29380042}, issn = {1432-0991}, mesh = {Anti-Infective Agents/chemistry/pharmacology ; Antioxidants/chemistry/pharmacology ; Bacteria/*metabolism ; Biofilms/drug effects ; Cyanates/metabolism ; Cyanides/*metabolism ; Escherichia coli/drug effects ; Oxidation-Reduction/drug effects ; Pseudomonas aeruginosa/drug effects ; Pterins/*chemistry/*pharmacology ; }, abstract = {Pterin is a member of the compounds known as pteridines. They have the same nucleus of 2-amino-4-hydroxypteridine (pterin); however, the side-chain is different at the position 6, and the state of oxidation of the ring may exist in different form viz. tetrahydro, dihydro, or a fully oxidized form. In the present study, the microorganisms able to utilize cyanide, and heavy metals have been tested for the efficient production of pterin compound. The soil samples contaminated with cyanide and heavy metals were collected from Salem steel industries, Tamil Nadu, India. Out of 77 isolated strains, 40 isolates were found to utilize sodium cyanate as nitrogen source at different concentrations. However, only 13 isolates were able to tolerate maximum concentration (60 mM) of sodium cyanate and were screened for pterin production. Among the 13 isolates, only 1 organism showed maximum production of pterin, and the same was identified as Bacillus pumilus SVD06. The compound was extracted and purified by preparative high-performance liquid chromatography and analyzed by UV/visible, FTIR, and fluorescent spectrum. The antioxidant property of the purified pterin compound was determined by cyclic voltammetry. In addition, antimicrobial activity of pterin was also studied which was substantiated by antagonistic activity against Escherichia coli, and Pseudomonas aeruginosa. Besides that the pterin compound was proved to inhibit the formation of biofilm. The extracted pterin compounds could be proposed further not only for antioxidant and antimicrobial but also for its potency to aid as anticancer and psychotic drugs in future.}, } @article {pmid29380035, year = {2018}, author = {Haug, C and Rötzer, MAIN}, title = {The ontogeny of Limulus polyphemus (Xiphosura s. str., Euchelicerata) revised: looking "under the skin".}, journal = {Development genes and evolution}, volume = {228}, number = {1}, pages = {49-61}, pmid = {29380035}, issn = {1432-041X}, support = {HA 7066/3-1//Deutsche Forschungsgemeinschaft/International ; }, mesh = {Animals ; Embryonic Development ; Extremities/embryology ; Horseshoe Crabs/*embryology/ultrastructure ; Optical Imaging ; }, abstract = {In recent years, methods for investigating the exo-morphology of zoological specimens have seen large improvements. Among new approaches, auto-fluorescence imaging offers possibilities to document specimens under high resolution without introducing additional artifacts as, for example, seen in scanning electron microscopy (SEM) imaging. Additionally, while SEM imaging is restricted to the outer morphology of the current instar, auto-fluorescence imaging can be used to document changes of the outer morphology of the next instar underneath the cuticle of the current instar. Thus, reinvestigating seemingly well known species with these methods may lead to interesting new insights. Here we reinvestigate the late embryonic development of the xiphosuran ("sword tail") Limulus polyphemus, which is often treated as a proxy for early eucheliceratan evolution. In addition to entire specimens, the appendages of the embryos were dissected off and documented separately with composite-autofluorescence microscopy. Based on these data, we can distinguish six developmental stages. These stages do not match exactly the formerly described stages, as these were largely based on SEM investigation. Our stages appear to represent earlier or later phases within what has in other studies been identified as one stage. This finer subdivision is visible as we can see the developing cuticle under the outer cuticle. In comparison to data from fossil xiphosurans, our results and those of other studies on the ontogeny of L. polyphemus point to a derived mode of development in this species, which argues against the idea of L. polyphemus as a "living fossil."}, } @article {pmid29379986, year = {2018}, author = {Dashevsky, D and Fry, BG}, title = {Ancient Diversification of Three-Finger Toxins in Micrurus Coral Snakes.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {58-67}, pmid = {29379986}, issn = {1432-1432}, abstract = {Coral snakes, most notably the genus Micrurus, are the only terrestrial elapid snakes in the Americas. Elapid venoms are generally known for their potent neurotoxicity which is usually caused by Three-Finger Toxin (3FTx) proteins. These toxins can have a wide array of functions that have been characterized from the venom of other elapids. We examined publicly available sequences from Micrurus 3FTx to show that they belong to 8 monophyletic clades that diverged as deep in the 3FTx phylogenetic tree as the other clades with characterized functions. Functional residues from previously characterized clades of 3FTx are not well conserved in most of the Micrurus toxin clades. We also analyzed the patterns of selection on these toxins and find that they have been diversifying at different rates, with some having undergone extreme diversifying selection. This suggests that Micrurus 3FTx may contain a previously underappreciated functional diversity that has implications for the clinical outcomes of bite victims, the evolution and ecology of the genus, as well as the potential for biodiscovery efforts focusing on these toxins.}, } @article {pmid29379217, year = {2018}, author = {Hofer, U}, title = {Marine Microbiology: Climate change boosts cyanobacteria.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {122-123}, pmid = {29379217}, issn = {1740-1534}, } @article {pmid29379216, year = {2018}, author = {Almeida, A and Shao, Y}, title = {Genome watch: Keeping tally in the microbiome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {124}, pmid = {29379216}, issn = {1740-1534}, abstract = {This month's Genome Watch highlights how the development of new approaches for quantifying the human microbiome may pave the way for a better understanding of microbial shifts in the context of human health and disease.}, } @article {pmid29379215, year = {2018}, author = {Poole, P and Ramachandran, V and Terpolilli, J}, title = {Rhizobia: from saprophytes to endosymbionts.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {5}, pages = {291-303}, pmid = {29379215}, issn = {1740-1534}, support = {BB/F004753/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/F013159/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Rhizobia are some of the best-studied plant microbiota. These oligotrophic Alphaproteobacteria or Betaproteobacteria form symbioses with their legume hosts. Rhizobia must exist in soil and compete with other members of the microbiota before infecting legumes and forming N2-fixing bacteroids. These dramatic lifestyle and developmental changes are underpinned by large genomes and even more complex pan-genomes, which encompass the whole population and are subject to rapid genetic exchange. The ability to respond to plant signals and chemoattractants and to colonize nutrient-rich roots are crucial for the competitive success of these bacteria. The availability of a large body of genomic, physiological, biochemical and ecological studies makes rhizobia unique models for investigating community interactions and plant colonization.}, } @article {pmid29379214, year = {2018}, author = {Du Toit, A}, title = {Bacterial pathogenesis: Don't stress and repair the damage.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {122-123}, pmid = {29379214}, issn = {1740-1534}, } @article {pmid29379210, year = {2018}, author = {Chen, J and Yang, YF and Yang, Y and Zou, P and Chen, J and He, Y and Shui, SL and Cui, YR and Bai, R and Liang, YJ and Hu, Y and Jiang, B and Lu, L and Zhang, X and Liu, J and Xu, J}, title = {AXL promotes Zika virus infection in astrocytes by antagonizing type I interferon signalling.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {302-309}, doi = {10.1038/s41564-017-0092-4}, pmid = {29379210}, issn = {2058-5276}, abstract = {Zika virus (ZIKV) is associated with neonatal microcephaly and Guillain-Barré syndrome1,2. While progress has been made in understanding the causal link between ZIKV infection and microcephaly3-9, the life cycle and pathogenesis of ZIKV are less well understood. In particular, there are conflicting reports on the role of AXL, a TAM family kinase receptor that was initially described as the entry receptor for ZIKV10-22. Here, we show that while genetic ablation of AXL protected primary human astrocytes and astrocytoma cell lines from ZIKV infection, AXL knockout did not block the entry of ZIKV. We found, instead, that the presence of AXL attenuated the ZIKV-induced activation of type I interferon (IFN) signalling genes, including several type I IFNs and IFN-stimulating genes. Knocking out type I IFN receptor α chain (IFNAR1) restored the vulnerability of AXL knockout astrocytes to ZIKV infection. Further experiments suggested that AXL regulates the expression of SOCS1, a known type I IFN signalling suppressor, in a STAT1/STAT2-dependent manner. Collectively, our results demonstrate that AXL is unlikely to function as an entry receptor for ZIKV and may instead promote ZIKV infection in human astrocytes by antagonizing type I IFN signalling.}, } @article {pmid29379209, year = {2018}, author = {Nivala, J and Shipman, SL and Church, GM}, title = {Spontaneous CRISPR loci generation in vivo by non-canonical spacer integration.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {310-318}, pmid = {29379209}, issn = {2058-5276}, support = {R01 MH103910/MH/NIMH NIH HHS/United States ; RM1 HG008525/HG/NHGRI NIH HHS/United States ; }, abstract = {The adaptation phase of CRISPR-Cas immunity depends on the precise integration of short segments of foreign DNA (spacers) into a specific genomic location within the CRISPR locus by the Cas1-Cas2 integration complex. Although off-target spacer integration outside of canonical CRISPR arrays has been described in vitro, no evidence of non-specific integration activity has been found in vivo. Here, we show that non-canonical off-target integrations can occur within bacterial chromosomes at locations that resemble the native CRISPR locus by characterizing hundreds of off-target integration locations within Escherichia coli. Considering whether such promiscuous Cas1-Cas2 activity could have an evolutionary role through the genesis of neo-CRISPR loci, we combed existing CRISPR databases and available genomes for evidence of off-target integration activity. This search uncovered several putative instances of naturally occurring off-target spacer integration events within the genomes of Yersinia pestis and Sulfolobus islandicus. These results are important in understanding alternative routes to CRISPR array genesis and evolution, as well as in the use of spacer acquisition in technological applications.}, } @article {pmid29379208, year = {2018}, author = {Probst, AJ and Ladd, B and Jarett, JK and Geller-McGrath, DE and Sieber, CMK and Emerson, JB and Anantharaman, K and Thomas, BC and Malmstrom, RR and Stieglmeier, M and Klingl, A and Woyke, T and Ryan, MC and Banfield, JF}, title = {Differential depth distribution of microbial function and putative symbionts through sediment-hosted aquifers in the deep terrestrial subsurface.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {328-336}, doi = {10.1038/s41564-017-0098-y}, pmid = {29379208}, issn = {2058-5276}, abstract = {An enormous diversity of previously unknown bacteria and archaea has been discovered recently, yet their functional capacities and distributions in the terrestrial subsurface remain uncertain. Here, we continually sampled a CO2-driven geyser (Colorado Plateau, Utah, USA) over its 5-day eruption cycle to test the hypothesis that stratified, sandstone-hosted aquifers sampled over three phases of the eruption cycle have microbial communities that differ both in membership and function. Genome-resolved metagenomics, single-cell genomics and geochemical analyses confirmed this hypothesis and linked microorganisms to groundwater compositions from different depths. Autotrophic Candidatus "Altiarchaeum sp." and phylogenetically deep-branching nanoarchaea dominate the deepest groundwater. A nanoarchaeon with limited metabolic capacity is inferred to be a potential symbiont of the Ca. "Altiarchaeum". Candidate Phyla Radiation bacteria are also present in the deepest groundwater and they are relatively abundant in water from intermediate depths. During the recovery phase of the geyser, microaerophilic Fe- and S-oxidizers have high in situ genome replication rates. Autotrophic Sulfurimonas sustained by aerobic sulfide oxidation and with the capacity for N2 fixation dominate the shallow aquifer. Overall, 104 different phylum-level lineages are present in water from these subsurface environments, with uncultivated archaea and bacteria partitioned to the deeper subsurface.}, } @article {pmid29379207, year = {2018}, author = {Qiu, X and Lei, Y and Yang, P and Gao, Q and Wang, N and Cao, L and Yuan, S and Huang, X and Deng, Y and Ma, W and Ding, T and Zhang, F and Wu, X and Hu, J and Liu, SL and Qin, C and Wang, X and Xu, Z and Rao, Z}, title = {Structural basis for neutralization of Japanese encephalitis virus by two potent therapeutic antibodies.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {287-294}, doi = {10.1038/s41564-017-0099-x}, pmid = {29379207}, issn = {2058-5276}, abstract = {Japanese encephalitis virus (JEV), closely related to dengue, Zika, yellow fever and West Nile viruses, remains neglected and not well characterized 1 . JEV is the leading causative agent of encephalitis, and is responsible for thousands of deaths each year in Asia. Humoral immunity is essential for protecting against flavivirus infections and passive immunization has been demonstrated to be effective in curing disease2,3. Here, we demonstrate that JEV-specific monoclonal antibodies, 2F2 and 2H4, block attachment of the virus to its receptor and also prevent fusion of the virus. Neutralization of JEV by these antibodies is exceptionally potent and confers clear therapeutic benefit in mouse models. A single 20 μg dose of these antibodies resulted in 100% survival and complete clearance of JEV from the brains of mice. The 4.7 Å and 4.6 Å resolution cryo-electron microscopy structures of JEV-2F2-Fab and JEV-2H4-Fab complexes, together with the crystal structure of 2H4 Fab and our recent near-atomic structure of JEV 4 , unveil the nature and location of epitopes targeted by the antibodies. Both 2F2 and 2H4 Fabs bind quaternary epitopes that span across three adjacent envelope proteins. Our results provide a structural and molecular basis for the application of 2F2 and 2H4 to treat JEV infection.}, } @article {pmid29379200, year = {2018}, author = {Alasoo, K and Rodrigues, J and Mukhopadhyay, S and Knights, AJ and Mann, AL and Kundu, K and , and Hale, C and Dougan, G and Gaffney, DJ}, title = {Shared genetic effects on chromatin and gene expression indicate a role for enhancer priming in immune response.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {424-431}, doi = {10.1038/s41588-018-0046-7}, pmid = {29379200}, issn = {1546-1718}, abstract = {Regulatory variants are often context specific, modulating gene expression in a subset of possible cellular states. Although these genetic effects can play important roles in disease, the molecular mechanisms underlying context specificity are poorly understood. Here, we identified shared quantitative trait loci (QTLs) for chromatin accessibility and gene expression in human macrophages exposed to IFNγ, Salmonella and IFNγ plus Salmonella. We observed that ~60% of stimulus-specific expression QTLs with a detectable effect on chromatin altered the chromatin accessibility in naive cells, thus suggesting that they perturb enhancer priming. Such variants probably influence binding of cell-type-specific transcription factors, such as PU.1, which can then indirectly alter the binding of stimulus-specific transcription factors, such as NF-κB or STAT2. Thus, although chromatin accessibility assays are powerful for fine-mapping causal regulatory variants, detecting their downstream effects on gene expression will be challenging, requiring profiling of large numbers of stimulated cellular states and time points.}, } @article {pmid29379199, year = {2018}, author = {Zeid, R and Lawlor, MA and Poon, E and Reyes, JM and Fulciniti, M and Lopez, MA and Scott, TG and Nabet, B and Erb, MA and Winter, GE and Jacobson, Z and Polaski, DR and Karlin, KL and Hirsch, RA and Munshi, NP and Westbrook, TF and Chesler, L and Lin, CY and Bradner, JE}, title = {Enhancer invasion shapes MYCN-dependent transcriptional amplification in neuroblastoma.}, journal = {Nature genetics}, volume = {50}, number = {4}, pages = {515-523}, doi = {10.1038/s41588-018-0044-9}, pmid = {29379199}, issn = {1546-1718}, support = {P01 CA155258/CA/NCI NIH HHS/United States ; R01 CA215452/CA/NCI NIH HHS/United States ; }, abstract = {Amplification of the locus encoding the oncogenic transcription factor MYCN is a defining feature of high-risk neuroblastoma. Here we present the first dynamic chromatin and transcriptional landscape of MYCN perturbation in neuroblastoma. At oncogenic levels, MYCN associates with E-box binding motifs in an affinity-dependent manner, binding to strong canonical E-boxes at promoters and invading abundant weaker non-canonical E-boxes clustered at enhancers. Loss of MYCN leads to a global reduction in transcription, which is most pronounced at MYCN target genes with the greatest enhancer occupancy. These highly occupied MYCN target genes show tissue-specific expression and are linked to poor patient survival. The activity of genes with MYCN-occupied enhancers is dependent on the tissue-specific transcription factor TWIST1, which co-occupies enhancers with MYCN and is required for MYCN-dependent proliferation. These data implicate tissue-specific enhancers in defining often highly tumor-specific 'MYC target gene signatures' and identify disruption of the MYCN enhancer regulatory axis as a promising therapeutic strategy in neuroblastoma.}, } @article {pmid29379198, year = {2018}, author = {Chang, J and Zhong, R and Tian, J and Li, J and Zhai, K and Ke, J and Lou, J and Chen, W and Zhu, B and Shen, N and Zhang, Y and Zhu, Y and Gong, Y and Yang, Y and Zou, D and Peng, X and Zhang, Z and Zhang, X and Huang, K and Wu, T and Wu, C and Miao, X and Lin, D}, title = {Exome-wide analyses identify low-frequency variant in CYP26B1 and additional coding variants associated with esophageal squamous cell carcinoma.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {338-343}, doi = {10.1038/s41588-018-0045-8}, pmid = {29379198}, issn = {1546-1718}, abstract = {Genome-wide association studies have identified common variants associated with risk of esophageal squamous cell carcinoma (ESCC). However, these common variants cannot explain all heritability of ESCC. Here we report an exome-wide interrogation of 3,714 individuals with ESCC and 3,880 controls for low-frequency susceptibility loci, with two independent replication samples comprising 7,002 cases and 8,757 controls. We found six new susceptibility loci in CCHCR1, TCN2, TNXB, LTA, CYP26B1 and FASN (P = 7.77 × 10-24 to P = 1.49 × 10-11), and three low-frequency variants had relatively high effect size (odds ratio > 1.5). Individuals with the rs138478634-GA genotype had significantly lower levels of serum all-trans retinoic acid, an anticancer nutrient, than those with the rs138478634-GG genotype (P = 0.0004), most likely due to an enhanced capacity of variant CYP26B1 to catabolize this agent. These findings emphasize the important role of rare coding variants in the development of ESCC.}, } @article {pmid29379197, year = {2018}, author = {Olley, G and Ansari, M and Bengani, H and Grimes, GR and Rhodes, J and von Kriegsheim, A and Blatnik, A and Stewart, FJ and Wakeling, E and Carroll, N and Ross, A and Park, SM and Bickmore, WA and Pradeepa, MM and FitzPatrick, DR and , }, title = {BRD4 interacts with NIPBL and BRD4 is mutated in a Cornelia de Lange-like syndrome.}, journal = {Nature genetics}, volume = {50}, number = {3}, pages = {329-332}, doi = {10.1038/s41588-018-0042-y}, pmid = {29379197}, issn = {1546-1718}, support = {MC_PC_U127527202//Medical Research Council/United Kingdom ; MC_PC_U127561093//Medical Research Council/United Kingdom ; }, abstract = {We found that the clinical phenotype associated with BRD4 haploinsufficiency overlapped with that of Cornelia de Lange syndrome (CdLS), which is most often caused by mutation of NIPBL. More typical CdLS was observed with a de novo BRD4 missense variant, which retained the ability to coimmunoprecipitate with NIPBL, but bound poorly to acetylated histones. BRD4 and NIPBL displayed correlated binding at super-enhancers and appeared to co-regulate developmental gene expression.}, } @article {pmid29379187, year = {2018}, author = {Danko, CG and Choate, LA and Marks, BA and Rice, EJ and Wang, Z and Chu, T and Martins, AL and Dukler, N and Coonrod, SA and Tait Wojno, ED and Lis, JT and Kraus, WL and Siepel, A}, title = {Dynamic evolution of regulatory element ensembles in primate CD4+ T cells.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {537-548}, pmid = {29379187}, issn = {2397-334X}, support = {R01 GM102192/GM/NIGMS NIH HHS/United States ; R01 DK058110/DK/NIDDK NIH HHS/United States ; R35 GM127070/GM/NIGMS NIH HHS/United States ; R01 HG009309/HG/NHGRI NIH HHS/United States ; K22 AI116729/AI/NIAID NIH HHS/United States ; R01 AI132708/AI/NIAID NIH HHS/United States ; P30 CA045508/CA/NCI NIH HHS/United States ; R01 HG007070/HG/NHGRI NIH HHS/United States ; U01 HL129958/HL/NHLBI NIH HHS/United States ; }, abstract = {How evolutionary changes at enhancers affect the transcription of target genes remains an important open question. Previous comparative studies of gene expression have largely measured the abundance of messenger RNA, which is affected by post-transcriptional regulatory processes, hence limiting inferences about the mechanisms underlying expression differences. Here, we directly measured nascent transcription in primate species, allowing us to separate transcription from post-transcriptional regulation. We used precision run-on and sequencing to map RNA polymerases in resting and activated CD4+ T cells in multiple human, chimpanzee and rhesus macaque individuals, with rodents as outgroups. We observed general conservation in coding and non-coding transcription, punctuated by numerous differences between species, particularly at distal enhancers and non-coding RNAs. Genes regulated by larger numbers of enhancers are more frequently transcribed at evolutionarily stable levels, despite reduced conservation at individual enhancers. Adaptive nucleotide substitutions are associated with lineage-specific transcription and at one locus, SGPP2, we predict and experimentally validate that multiple substitutions contribute to human-specific transcription. Collectively, our findings suggest a pervasive role for evolutionary compensation across ensembles of enhancers that jointly regulate target genes.}, } @article {pmid29379186, year = {2018}, author = {Lacadie, SA and Ohler, U}, title = {Redundant regulation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {418-419}, doi = {10.1038/s41559-018-0479-5}, pmid = {29379186}, issn = {2397-334X}, } @article {pmid29379185, year = {2018}, author = {Rolland, J and Silvestro, D and Schluter, D and Guisan, A and Broennimann, O and Salamin, N}, title = {The impact of endothermy on the climatic niche evolution and the distribution of vertebrate diversity.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {459-464}, doi = {10.1038/s41559-017-0451-9}, pmid = {29379185}, issn = {2397-334X}, abstract = {Understanding the mechanisms by which the abiotic and biotic requirements of species, or ecological niches, change over time is a central issue in evolutionary biology. Niche evolution is poorly understood at both the macroecological and macroevolutionary scales, as niches can shift over short periods of time but appear to change more slowly over longer timescales. Although reconstructing past niches has always been a major concern for palaeontologists and evolutionary biologists, only a few recent studies have successfully determined the factors that affect niche evolution. Here, we compare the evolution of climatic niches in four main groups of terrestrial vertebrates using a modelling approach integrating both palaeontological and neontological data, and large-scale datasets that contain information on the current distributions, phylogenetic relationships and fossil records for a total of 11,465 species. By reconstructing historical shifts in geographical ranges and climatic niches, we show that niche shifts are significantly faster in endotherms (birds and mammals) than in ectotherms (squamates and amphibians). We further demonstrate that the diversity patterns of the four clades are directly affected by the rate of niche evolution, with fewer latitudinal shifts in ectotherms.}, } @article {pmid29379184, year = {2018}, author = {Algar, AC and Tarr, S}, title = {Fossils, phylogenies and the evolving climate niche.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {414-415}, doi = {10.1038/s41559-018-0480-z}, pmid = {29379184}, issn = {2397-334X}, } @article {pmid29379183, year = {2018}, author = {Sallam, HM and Gorscak, E and O'Connor, PM and El-Dawoudi, IA and El-Sayed, S and Saber, S and Kora, MA and Sertich, JJW and Seiffert, ER and Lamanna, MC}, title = {New Egyptian sauropod reveals Late Cretaceous dinosaur dispersal between Europe and Africa.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {445-451}, doi = {10.1038/s41559-017-0455-5}, pmid = {29379183}, issn = {2397-334X}, abstract = {Prominent hypotheses advanced over the past two decades have sought to characterize the Late Cretaceous continental vertebrate palaeobiogeography of Gondwanan landmasses, but have proved difficult to test because terrestrial vertebrates from the final ~30 million years of the Mesozoic are extremely rare and fragmentary on continental Africa (including the then-conjoined Arabian Peninsula but excluding the island of Madagascar). Here we describe a new titanosaurian sauropod dinosaur, Mansourasaurus shahinae gen. et sp. nov., from the Upper Cretaceous (Campanian) Quseir Formation of the Dakhla Oasis of the Egyptian Western Desert. Represented by an associated partial skeleton that includes cranial elements, Mansourasaurus is the most completely preserved land-living vertebrate from the post-Cenomanian Cretaceous (~94-66 million years ago) of the African continent. Phylogenetic analyses demonstrate that Mansourasaurus is nested within a clade of penecontemporaneous titanosaurians from southern Europe and eastern Asia, thereby providing the first unambiguous evidence for a post-Cenomanian Cretaceous continental vertebrate clade that inhabited both Africa and Europe. The close relationship of Mansourasaurus to coeval Eurasian titanosaurians indicates that terrestrial vertebrate dispersal occurred between Eurasia and northern Africa after the tectonic separation of the latter from South America ~100 million years ago. These findings counter hypotheses that dinosaur faunas of the African mainland were completely isolated during the post-Cenomanian Cretaceous.}, } @article {pmid29379182, year = {2018}, author = {Jiménez-Alfaro, B and Girardello, M and Chytrý, M and Svenning, JC and Willner, W and Gégout, JC and Agrillo, E and Campos, JA and Jandt, U and Kącki, Z and Šilc, U and Slezák, M and Tichý, L and Tsiripidis, I and Turtureanu, PD and Ujházyová, M and Wohlgemuth, T}, title = {History and environment shape species pools and community diversity in European beech forests.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {483-490}, doi = {10.1038/s41559-017-0462-6}, pmid = {29379182}, issn = {2397-334X}, abstract = {A central hypothesis of ecology states that regional diversity influences local diversity through species-pool effects. Species pools are supposedly shaped by large-scale factors and then filtered into ecological communities, but understanding these processes requires the analysis of large datasets across several regions. Here, we use a framework of community assembly at a continental scale to test the relative influence of historical and environmental drivers, in combination with regional or local species pools, on community species richness and community completeness. Using 42,173 vegetation plots sampled across European beech forests, we found that large-scale factors largely accounted for species pool sizes. At the regional scale, main predictors reflected historical contingencies related to post-glacial dispersal routes, whereas at the local scale, the influence of environmental filters was predominant. Proximity to Quaternary refugia and high precipitation were the main factors supporting community species richness, especially among beech forest specialist plants. Models for community completeness indicate the influence of large-scale factors, further suggesting community saturation as a result of dispersal limitation or biotic interactions. Our results empirically demonstrate how historical factors complement environmental gradients to provide a better understanding of biodiversity patterns across multiple regions.}, } @article {pmid29379135, year = {2018}, author = {Langmead, B and Nellore, A}, title = {Cloud computing for genomic data analysis and collaboration.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {208-219}, pmid = {29379135}, issn = {1471-0064}, support = {R01 GM118568/GM/NIGMS NIH HHS/United States ; }, abstract = {Next-generation sequencing has made major strides in the past decade. Studies based on large sequencing data sets are growing in number, and public archives for raw sequencing data have been doubling in size every 18 months. Leveraging these data requires researchers to use large-scale computational resources. Cloud computing, a model whereby users rent computers and storage from large data centres, is a solution that is gaining traction in genomics research. Here, we describe how cloud computing is used in genomics for research and large-scale collaborations, and argue that its elasticity, reproducibility and privacy features make it ideally suited for the large-scale reanalysis of publicly available archived data, including privacy-protected data.}, } @article {pmid29379134, year = {2018}, author = {Trenkmann, M}, title = {Plant genetics: Parasites plant microRNAs in the host.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {127}, pmid = {29379134}, issn = {1471-0064}, } @article {pmid29378971, year = {2018}, author = {Reddy, P and Sevick, EM and Williams, DRM}, title = {Triangular cyclic rotaxanes: Size, fluctuations, and switching properties.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9367-9372}, pmid = {29378971}, issn = {1091-6490}, abstract = {We examine one of the simplest cyclic rotaxanes-a molecule made from three rods with variable length between 0 and L. This [3]rotaxane, unlike a traditional molecule, shows significant size and shape fluctuations. We quantify these using a number of different measures. In particular, we show that the average angles are [Formula: see text], and [Formula: see text] and the most populated lengths lie at [Formula: see text], and [Formula: see text] The triangles are usually obtuse. We discuss the area allowed within the triangle for inclusion compounds. Inspired by the linear rotaxane switches, we also consider the statistical mechanics of switching when stations with attractive interactions promote small-cycle areas.}, } @article {pmid29378970, year = {2018}, author = {di Santo, S and Villegas, P and Burioni, R and Muñoz, MA}, title = {Landau-Ginzburg theory of cortex dynamics: Scale-free avalanches emerge at the edge of synchronization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1356-E1365}, pmid = {29378970}, issn = {1091-6490}, mesh = {Action Potentials ; Brain/*physiology ; Cerebral Cortex/*physiology ; Electrophysiological Phenomena ; Humans ; *Models, Neurological ; Nerve Net/*physiology ; Neuronal Plasticity ; Neurons/*physiology ; Sleep/*physiology ; }, abstract = {Understanding the origin, nature, and functional significance of complex patterns of neural activity, as recorded by diverse electrophysiological and neuroimaging techniques, is a central challenge in neuroscience. Such patterns include collective oscillations emerging out of neural synchronization as well as highly heterogeneous outbursts of activity interspersed by periods of quiescence, called "neuronal avalanches." Much debate has been generated about the possible scale invariance or criticality of such avalanches and its relevance for brain function. Aimed at shedding light onto this, here we analyze the large-scale collective properties of the cortex by using a mesoscopic approach following the principle of parsimony of Landau-Ginzburg. Our model is similar to that of Wilson-Cowan for neural dynamics but crucially, includes stochasticity and space; synaptic plasticity and inhibition are considered as possible regulatory mechanisms. Detailed analyses uncover a phase diagram including down-state, synchronous, asynchronous, and up-state phases and reveal that empirical findings for neuronal avalanches are consistently reproduced by tuning our model to the edge of synchronization. This reveals that the putative criticality of cortical dynamics does not correspond to a quiescent-to-active phase transition as usually assumed in theoretical approaches but to a synchronization phase transition, at which incipient oscillations and scale-free avalanches coexist. Furthermore, our model also accounts for up and down states as they occur (e.g., during deep sleep). This approach constitutes a framework to rationalize the possible collective phases and phase transitions of cortical networks in simple terms, thus helping to shed light on basic aspects of brain functioning from a very broad perspective.}, } @article {pmid29378969, year = {2018}, author = {Mollica, NR and Guo, W and Cohen, AL and Huang, KF and Foster, GL and Donald, HK and Solow, AR}, title = {Ocean acidification affects coral growth by reducing skeletal density.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1754-1759}, pmid = {29378969}, issn = {1091-6490}, abstract = {Ocean acidification (OA) is considered an important threat to coral reef ecosystems, because it reduces the availability of carbonate ions that reef-building corals need to produce their skeletons. However, while theory predicts that coral calcification rates decline as carbonate ion concentrations decrease, this prediction is not consistently borne out in laboratory manipulation experiments or in studies of corals inhabiting naturally low-pH reefs today. The skeletal growth of corals consists of two distinct processes: extension (upward growth) and densification (lateral thickening). Here, we show that skeletal density is directly sensitive to changes in seawater carbonate ion concentration and thus, to OA, whereas extension is not. We present a numerical model of Porites skeletal growth that links skeletal density with the external seawater environment via its influence on the chemistry of coral calcifying fluid. We validate the model using existing coral skeletal datasets from six Porites species collected across five reef sites and use this framework to project the impact of 21st century OA on Porites skeletal density across the global tropics. Our model predicts that OA alone will drive up to 20.3 ± 5.4% decline in the skeletal density of reef-building Porites corals.}, } @article {pmid29378968, year = {2018}, author = {Bétourné, A and Szelechowski, M and Thouard, A and Abrial, E and Jean, A and Zaidi, F and Foret, C and Bonnaud, EM and Charlier, CM and Suberbielle, E and Malnou, CE and Granon, S and Rampon, C and Gonzalez-Dunia, D}, title = {Hippocampal expression of a virus-derived protein impairs memory in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1611-1616}, pmid = {29378968}, issn = {1091-6490}, mesh = {Animals ; Borna Disease/metabolism/pathology/*virology ; Borna disease virus/*physiology ; Cells, Cultured ; Cognition Disorders/*etiology/metabolism/pathology ; Dentate Gyrus/metabolism/pathology/virology ; Hippocampus/metabolism/pathology/*virology ; Memory, Long-Term/*physiology ; Mice ; Mutation ; Neuronal Plasticity ; Neurons/metabolism/pathology/virology ; Phosphoproteins/genetics/*metabolism ; Phosphorylation ; Protein Kinase C/genetics/*metabolism ; Viral Structural Proteins/genetics/*metabolism ; }, abstract = {The analysis of the biology of neurotropic viruses, notably of their interference with cellular signaling, provides a useful tool to get further insight into the role of specific pathways in the control of behavioral functions. Here, we exploited the natural property of a viral protein identified as a major effector of behavioral disorders during infection. We used the phosphoprotein (P) of Borna disease virus, which acts as a decoy substrate for protein kinase C (PKC) when expressed in neurons and disrupts synaptic plasticity. By a lentiviral-based strategy, we directed the singled-out expression of P in the dentate gyrus of the hippocampus and we examined its impact on mouse behavior. Mice expressing the P protein displayed increased anxiety and impaired long-term memory in contextual and spatial memory tasks. Interestingly, these effects were dependent on P protein phosphorylation by PKC, as expression of a mutant form of P devoid of its PKC phosphorylation sites had no effect on these behaviors. We also revealed features of behavioral impairment induced by P protein expression but that were independent of its phosphorylation by PKC. Altogether, our findings provide insight into the behavioral correlates of viral infection, as well as into the impact of virus-mediated alterations of the PKC pathway on behavioral functions.}, } @article {pmid29378967, year = {2018}, author = {Bogoslowski, A and Butcher, EC and Kubes, P}, title = {Neutrophils recruited through high endothelial venules of the lymph nodes via PNAd intercept disseminating Staphylococcus aureus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2449-2454}, pmid = {29378967}, issn = {1091-6490}, support = {R01 CA169354/CA/NCI NIH HHS/United States ; R01 GM037734/GM/NIGMS NIH HHS/United States ; R37 AI047822/AI/NIAID NIH HHS/United States ; //CIHR/Canada ; }, mesh = {Animals ; Endothelium/*immunology ; Humans ; L-Selectin/metabolism ; Lymph Nodes/cytology/*immunology/microbiology ; Lymphatic Vessels/*immunology ; Mice ; Neutrophils/*immunology ; Staphylococcal Infections/immunology ; Staphylococcus aureus/*immunology ; }, abstract = {Staphylococcus aureus is a skin- and respiratory tract-colonizing bacterium and is the leading cause of community-acquired skin infections. Dissemination of these bacteria into systemic circulation causes bacteremia, which has a high mortality rate. Therefore, understanding the immunologic barriers that prevent dissemination is critical to developing novel treatments. In this study, we demonstrate that an S. aureus breach across skin leads to some migration of the pathogen to the draining lymph node, but no further. While subcapsular sinus (SCS) macrophage in lymph nodes were important in detaining S. aureus, a rapid complement-dependent neutrophil recruitment (independent of the SCS macrophage) via high endothelial venules (HEVs) resulted in high numbers of neutrophils that intercepted the bacteria in the lymph nodes. Peripheral Node Addressin together with its two ligands, L-selectin and platelet P-selectin, are critical for recruiting neutrophils via the HEVs. Almost no neutrophils entered the lymph nodes via lymphatics. Neutrophils actively phagocytosed S. aureus and helped sterilize the lymph nodes and prevent dissemination to blood and other organs.}, } @article {pmid29378966, year = {2018}, author = {Essington, TE and Sanchirico, JN and Baskett, ML}, title = {Economic value of ecological information in ecosystem-based natural resource management depends on exploitation history.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1658-1663}, pmid = {29378966}, issn = {1091-6490}, mesh = {Animals ; Conservation of Natural Resources/*economics/*methods ; *Ecosystem ; Fisheries/*economics ; Fishes/*physiology ; Natural Resources/*supply & distribution ; Socioeconomic Factors ; }, abstract = {Ecosystem approaches to natural resource management are seen as a way to provide better outcomes for ecosystems and for people, yet the nature and strength of interactions among ecosystem components is usually unknown. Here we characterize the economic benefits of ecological knowledge through a simple model of fisheries that target a predator (piscivore) and its prey. We solve for the management (harvest) trajectory that maximizes net present value (NPV) for different ecological interactions and initial conditions that represent different levels of exploitation history. Optimal management trajectories generally approached similar harvest levels, but the pathways toward those levels varied considerably by ecological scenario. Application of the wrong harvest trajectory, which would happen if one type of ecological interaction were assumed but in fact another were occurring, generally led to only modest reductions in NPV. However, the risks were not equal across fleets: risks of incurring large losses of NPV and missing management targets were much higher in the fishery targeting piscivores, especially when piscivores were heavily depleted. Our findings suggest that the ecosystem approach might provide the greatest benefits when used to identify system states where management performs poorly with imperfect knowledge of system linkages so that management strategies can be adopted to avoid those states.}, } @article {pmid29378965, year = {2018}, author = {Bay, SN and Long, AB and Caspary, T}, title = {Disruption of the ciliary GTPase Arl13b suppresses Sonic hedgehog overactivation and inhibits medulloblastoma formation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1570-1575}, pmid = {29378965}, issn = {1091-6490}, support = {R01 NS090029/NS/NINDS NIH HHS/United States ; R35 GM122549/GM/NIGMS NIH HHS/United States ; R01 GM110663/GM/NIGMS NIH HHS/United States ; T32 GM008490/GM/NIGMS NIH HHS/United States ; T32 MH087977/MH/NIMH NIH HHS/United States ; P30 NS055077/NS/NINDS NIH HHS/United States ; }, mesh = {ADP-Ribosylation Factors/*physiology ; Animals ; Cells, Cultured ; Cerebellar Neoplasms/genetics/metabolism/*pathology ; Cilia/enzymology/*physiology ; Embryo, Mammalian/metabolism/pathology ; Female ; Fibroblasts/metabolism/pathology ; Hedgehog Proteins/genetics/*metabolism ; Humans ; Medulloblastoma/genetics/metabolism/*pathology ; Mice ; Mice, Knockout ; Osteonectin/genetics/*metabolism ; Signal Transduction ; }, abstract = {Medulloblastoma (MB) is the most common malignant pediatric brain tumor, and overactivation of the Sonic Hedgehog (Shh) signaling pathway, which requires the primary cilium, causes 30% of MBs. Current treatments have known negative side effects or resistance mechanisms, so new treatments are necessary. Shh signaling mutations, like those that remove Patched1 (Ptch1) or activate Smoothened (Smo), cause tumors dependent on the presence of cilia. Genetic ablation of cilia prevents these tumors by removing Gli activator, but cilia are a poor therapeutic target since they support many biological processes. A more appropriate strategy would be to identify a protein that functionally disentangles Gli activation and ciliogenesis. Our mechanistic understanding of the ciliary GTPase Arl13b predicts that it could be such a target. Arl13b mutants retain short cilia, and loss of Arl13b results in ligand-independent, constitutive, low-level pathway activation but prevents maximal signaling without disrupting Gli repressor. Here, we show that deletion of Arl13b reduced Shh signaling levels in the presence of oncogenic SmoA1, suggesting Arl13b acts downstream of known tumor resistance mechanisms. Knockdown of ARL13B in human MB cell lines and in primary mouse MB cell culture decreased proliferation. Importantly, loss of Arl13b in a Ptch1-deleted mouse model of MB inhibited tumor formation. Postnatal depletion of Arl13b does not lead to any overt phenotypes in the epidermis, liver, or cerebellum. Thus, our in vivo and in vitro studies demonstrate that disruption of Arl13b inhibits cilia-dependent oncogenic Shh overactivation.}, } @article {pmid29378964, year = {2018}, author = {FeldmanHall, O and Dunsmoor, JE and Tompary, A and Hunter, LE and Todorov, A and Phelps, EA}, title = {Stimulus generalization as a mechanism for learning to trust.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1690-E1697}, pmid = {29378964}, issn = {1091-6490}, mesh = {Amygdala/physiology ; Decision Making ; Games, Experimental ; *Generalization, Stimulus ; Humans ; *Learning ; Male ; Morals ; Perception ; Social Environment ; *Trust/psychology ; Young Adult ; }, abstract = {How do humans learn to trust unfamiliar others? Decisions in the absence of direct knowledge rely on our ability to generalize from past experiences and are often shaped by the degree of similarity between prior experience and novel situations. Here, we leverage a stimulus generalization framework to examine how perceptual similarity between known individuals and unfamiliar strangers shapes social learning. In a behavioral study, subjects play an iterative trust game with three partners who exhibit highly trustworthy, somewhat trustworthy, or highly untrustworthy behavior. After learning who can be trusted, subjects select new partners for a second game. Unbeknownst to subjects, each potential new partner was parametrically morphed with one of the three original players. Results reveal that subjects prefer to play with strangers who implicitly resemble the original player they previously learned was trustworthy and avoid playing with strangers resembling the untrustworthy player. These decisions to trust or distrust strangers formed a generalization gradient that converged toward baseline as perceptual similarity to the original player diminished. In a second imaging experiment we replicate these behavioral gradients and leverage multivariate pattern similarity analyses to reveal that a tuning profile of activation patterns in the amygdala selectively captures increasing perceptions of untrustworthiness. We additionally observe that within the caudate adaptive choices to trust rely on neural activation patterns similar to those elicited when learning about unrelated, but perceptually familiar, individuals. Together, these findings suggest an associative learning mechanism efficiently deploys moral information encoded from past experiences to guide future choice.}, } @article {pmid29378963, year = {2018}, author = {Wood, JG and Schwer, B and Wickremesinghe, PC and Hartnett, DA and Burhenn, L and Garcia, M and Li, M and Verdin, E and Helfand, SL}, title = {Sirt4 is a mitochondrial regulator of metabolism and lifespan in Drosophila melanogaster.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1564-1569}, pmid = {29378963}, issn = {1091-6490}, support = {P40 OD010949/OD/NIH HHS/United States ; R01 AG024353/AG/NIA NIH HHS/United States ; R37 AG016667/AG/NIA NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; P01 AG051449/AG/NIA NIH HHS/United States ; R01 AG016667/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified/genetics/*growth & development/*metabolism ; Drosophila melanogaster/genetics/*growth & development/*metabolism ; Fasting/physiology ; Female ; Fertility/physiology ; Glycolysis ; Homeostasis ; *Longevity ; Male ; Metabolomics ; Mitochondria/genetics/metabolism ; Mitochondrial Proteins/genetics/*metabolism ; Sirtuins/genetics/*metabolism ; }, abstract = {Sirtuins are an evolutionarily conserved family of NAD+-dependent deacylases that control metabolism, stress response, genomic stability, and longevity. Here, we show the sole mitochondrial sirtuin in Drosophila melanogaster, Sirt4, regulates energy homeostasis and longevity. Sirt4 knockout flies have a short lifespan, with increased sensitivity to starvation and decreased fertility and activity. In contrast, flies overexpressing Sirt4 either ubiquitously or specifically in the fat body are long-lived. Despite rapid starvation, Sirt4 knockout flies paradoxically maintain elevated levels of energy reserves, including lipids, glycogen, and trehalose, while fasting, suggesting an inability to properly catabolize stored energy. Metabolomic analysis indicates several specific pathways are affected in Sirt4 knockout flies, including glycolysis, branched-chain amino acid metabolism, and impaired catabolism of fatty acids with chain length C18 or greater. Together, these phenotypes point to a role for Sirt4 in mediating the organismal response to fasting, and ensuring metabolic homeostasis and longevity.}, } @article {pmid29378962, year = {2018}, author = {Thu, KL and Silvester, J and Elliott, MJ and Ba-Alawi, W and Duncan, MH and Elia, AC and Mer, AS and Smirnov, P and Safikhani, Z and Haibe-Kains, B and Mak, TW and Cescon, DW}, title = {Disruption of the anaphase-promoting complex confers resistance to TTK inhibitors in triple-negative breast cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1570-E1577}, pmid = {29378962}, issn = {1091-6490}, support = {//CIHR/Canada ; }, mesh = {Anaphase-Promoting Complex-Cyclosome/genetics/*metabolism ; Cell Cycle Proteins/*antagonists & inhibitors/metabolism ; Cell Line, Tumor ; *Drug Resistance, Neoplasm ; Female ; Genomic Instability/drug effects ; Humans ; Mitosis/drug effects ; Protein Kinase Inhibitors/*pharmacology ; Protein-Serine-Threonine Kinases/*antagonists & inhibitors/metabolism ; Protein-Tyrosine Kinases/*antagonists & inhibitors/metabolism ; Pyrazoles/*pharmacology ; Pyrimidines/*pharmacology ; Triple Negative Breast Neoplasms/drug therapy/*enzymology/genetics/physiopathology ; }, abstract = {TTK protein kinase (TTK), also known as Monopolar spindle 1 (MPS1), is a key regulator of the spindle assembly checkpoint (SAC), which functions to maintain genomic integrity. TTK has emerged as a promising therapeutic target in human cancers, including triple-negative breast cancer (TNBC). Several TTK inhibitors (TTKis) are being evaluated in clinical trials, and an understanding of the mechanisms mediating TTKi sensitivity and resistance could inform the successful development of this class of agents. We evaluated the cellular effects of the potent clinical TTKi CFI-402257 in TNBC models. CFI-402257 induced apoptosis and potentiated aneuploidy in TNBC lines by accelerating progression through mitosis and inducing mitotic segregation errors. We used genome-wide CRISPR/Cas9 screens in multiple TNBC cell lines to identify mechanisms of resistance to CFI-402257. Our functional genomic screens identified members of the anaphase-promoting complex/cyclosome (APC/C) complex, which promotes mitotic progression following inactivation of the SAC. Several screen candidates were validated to confer resistance to CFI-402257 and other TTKis using CRISPR/Cas9 and siRNA methods. These findings extend the observation that impairment of the APC/C enables cells to tolerate genomic instability caused by SAC inactivation, and support the notion that a measure of APC/C function could predict the response to TTK inhibition. Indeed, an APC/C gene expression signature is significantly associated with CFI-402257 response in breast and lung adenocarcinoma cell line panels. This expression signature, along with somatic alterations in genes involved in mitotic progression, represent potential biomarkers that could be evaluated in ongoing clinical trials of CFI-402257 or other TTKis.}, } @article {pmid29378961, year = {2018}, author = {Bulgari, D and Jha, A and Deitcher, DL and Levitan, ES}, title = {Myopic (HD-PTP, PTPN23) selectively regulates synaptic neuropeptide release.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1617-1622}, pmid = {29378961}, issn = {1091-6490}, support = {P40 OD018537/OD/NIH HHS/United States ; R01 NS032385/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Drosophila/growth & development/*metabolism ; Drosophila Proteins/*metabolism ; Exocytosis/*physiology ; Neuromuscular Junction/metabolism ; Neuropeptides/*metabolism ; Presynaptic Terminals/metabolism ; Protein Tyrosine Phosphatases/*metabolism ; Secretory Vesicles/*metabolism ; Synaptic Transmission ; Synaptic Vesicles/*metabolism ; }, abstract = {Neurotransmission is mediated by synaptic exocytosis of neuropeptide-containing dense-core vesicles (DCVs) and small-molecule transmitter-containing small synaptic vesicles (SSVs). Exocytosis of both vesicle types depends on Ca2+ and shared secretory proteins. Here, we show that increasing or decreasing expression of Myopic (mop, HD-PTP, PTPN23), a Bro1 domain-containing pseudophosphatase implicated in neuronal development and neuropeptide gene expression, increases synaptic neuropeptide stores at the Drosophila neuromuscular junction (NMJ). This occurs without altering DCV content or transport, but synaptic DCV number and age are increased. The effect on synaptic neuropeptide stores is accounted for by inhibition of activity-induced Ca2+-dependent neuropeptide release. cAMP-evoked Ca2+-independent synaptic neuropeptide release also requires optimal Myopic expression, showing that Myopic affects the DCV secretory machinery shared by cAMP and Ca2+ pathways. Presynaptic Myopic is abundant at early endosomes, but interaction with the endosomal sorting complex required for transport III (ESCRT III) protein (CHMP4/Shrub) that mediates Myopic's effect on neuron pruning is not required for control of neuropeptide release. Remarkably, in contrast to the effect on DCVs, Myopic does not affect release from SSVs. Therefore, Myopic selectively regulates synaptic DCV exocytosis that mediates peptidergic transmission at the NMJ.}, } @article {pmid29378960, year = {2018}, author = {Solé-Domènech, S and Rojas, AV and Maisuradze, GG and Scheraga, HA and Lobel, P and Maxfield, FR}, title = {Lysosomal enzyme tripeptidyl peptidase 1 destabilizes fibrillar Aβ by multiple endoproteolytic cleavages within the β-sheet domain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1493-1498}, pmid = {29378960}, issn = {1091-6490}, support = {R01 NS037918/NS/NINDS NIH HHS/United States ; R01 GM014312/GM/NIGMS NIH HHS/United States ; S10 OD016400/OD/NIH HHS/United States ; P30 NS046593/NS/NINDS NIH HHS/United States ; S10 RR024584/RR/NCRR NIH HHS/United States ; R37 DK027083/DK/NIDDK NIH HHS/United States ; }, mesh = {Aminopeptidases/genetics/*metabolism ; Amyloid/metabolism ; Amyloid beta-Peptides/chemistry/*metabolism ; Carbocyanines/chemistry ; Dipeptidyl-Peptidases and Tripeptidyl-Peptidases/genetics/*metabolism ; Fluorescent Dyes/chemistry ; Humans ; Hydrogen-Ion Concentration ; Lysosomes/enzymology ; Mass Spectrometry ; Models, Molecular ; Molecular Dynamics Simulation ; Peptide Fragments/chemistry/*metabolism ; Protein Conformation, beta-Strand ; Protein Domains ; Protein Stability ; Serine Proteases/genetics/*metabolism ; Time Factors ; }, abstract = {Accumulation of amyloid-beta (Aβ), which is associated with Alzheimer's disease, can be caused by excess production or insufficient clearance. Because of its β-sheet structure, fibrillar Aβ is resistant to proteolysis, which would contribute to slow degradation of Aβ plaques in vivo. Fibrillar Aβ can be internalized by microglia, which are the scavenger cells of the brain, but the fibrils are degraded only slowly in microglial lysosomes. Cathepsin B is a lysosomal protease that has been shown to proteolyze fibrillar Aβ. Tripeptidyl peptidase 1 (TPP1), a lysosomal serine protease, possesses endopeptidase activity and has been shown to cleave peptides between hydrophobic residues. Herein, we demonstrate that TPP1 is able to proteolyze fibrillar Aβ efficiently. Mass spectrometry analysis of peptides released from fibrillar Aβ digested with TPP1 reveals several endoproteolytic cleavages including some within β-sheet regions that are important for fibril formation. Using molecular dynamics simulations, we demonstrate that these cleavages destabilize fibrillar β-sheet structure. The demonstration that TPP1 can degrade fibrillar forms of Aβ provides insight into the turnover of fibrillar Aβ and may lead to new therapeutic methods to increase degradation of Aβ plaques.}, } @article {pmid29378959, year = {2018}, author = {Fang, Y and Hill, CM and Darcy, J and Reyes-Ordoñez, A and Arauz, E and McFadden, S and Zhang, C and Osland, J and Gao, J and Zhang, T and Frank, SJ and Javors, MA and Yuan, R and Kopchick, JJ and Sun, LY and Chen, J and Bartke, A}, title = {Effects of rapamycin on growth hormone receptor knockout mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1495-E1503}, pmid = {29378959}, issn = {1091-6490}, support = {K01 AG048264/AG/NIA NIH HHS/United States ; R01 AG019899/AG/NIA NIH HHS/United States ; R56 AG057734/AG/NIA NIH HHS/United States ; R01 AR048914/AR/NIAMS NIH HHS/United States ; R56 AG050531/AG/NIA NIH HHS/United States ; R21 AG038850/AG/NIA NIH HHS/United States ; R21 AG051869/AG/NIA NIH HHS/United States ; R01 GM089771/GM/NIGMS NIH HHS/United States ; R21 AG050225/AG/NIA NIH HHS/United States ; P01 AG031736/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Cytoplasm/drug effects/metabolism ; Female ; Immunosuppressive Agents/*pharmacology ; Insulin Resistance ; Longevity/*drug effects ; Male ; Mechanistic Target of Rapamycin Complex 1/*metabolism ; Mechanistic Target of Rapamycin Complex 2/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Knockout ; Receptors, Somatotropin/*physiology ; Signal Transduction ; Sirolimus/*pharmacology ; }, abstract = {It is well documented that inhibition of mTORC1 (defined by Raptor), a complex of mechanistic target of rapamycin (mTOR), extends life span, but less is known about the mechanisms by which mTORC2 (defined by Rictor) impacts longevity. Here, rapamycin (an inhibitor of mTOR) was used in GHR-KO (growth hormone receptor knockout) mice, which have suppressed mTORC1 and up-regulated mTORC2 signaling, to determine the effect of concurrently decreased mTORC1 and mTORC2 signaling on life span. We found that rapamycin extended life span in control normal (N) mice, whereas it had the opposite effect in GHR-KO mice. In the rapamycin-treated GHR-KO mice, mTORC2 signaling was reduced without further inhibition of mTORC1 in the liver, muscle, and s.c. fat. Glucose and lipid homeostasis were impaired, and old GHR-KO mice treated with rapamycin lost functional immune cells and had increased inflammation. In GHR-KO MEF cells, knockdown of Rictor, but not Raptor, decreased mTORC2 signaling. We conclude that drastic reduction of mTORC2 plays important roles in impaired longevity in GHR-KO mice via disruption of whole-body homeostasis.}, } @article {pmid29378958, year = {2018}, author = {Ortíz-Rentería, M and Juárez-Contreras, R and González-Ramírez, R and Islas, LD and Sierra-Ramírez, F and Llorente, I and Simon, SA and Hiriart, M and Rosenbaum, T and Morales-Lázaro, SL}, title = {TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1657-E1666}, pmid = {29378958}, issn = {1091-6490}, mesh = {Animals ; Capsaicin/metabolism ; Cell Line ; Cell Membrane/genetics/metabolism ; Female ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Pain/genetics/*metabolism ; Progesterone/metabolism ; Protein Binding ; Receptors, sigma/*metabolism ; Sensory Receptor Cells/metabolism ; TRPV Cation Channels/genetics/*metabolism ; }, abstract = {The Transient Receptor Potential Vanilloid 1 (TRPV1) ion channel is expressed in nociceptors where, when activated by chemical or thermal stimuli, it functions as an important transducer of painful and itch-related stimuli. Although the interaction of TRPV1 with proteins that regulate its function has been previously explored, their modulation by chaperones has not been elucidated, as is the case for other mammalian TRP channels. Here we show that TRPV1 physically interacts with the Sigma 1 Receptor (Sig-1R), a chaperone that binds progesterone, an antagonist of Sig-1R and an important neurosteroid associated to the modulation of pain. Antagonism of Sig-1R by progesterone results in the down-regulation of TRPV1 expression in the plasma membrane of sensory neurons and, consequently, a decrease in capsaicin-induced nociceptive responses. This is observed both in males treated with a synthetic antagonist of Sig-1R and in pregnant females where progesterone levels are elevated. This constitutes a previously undescribed mechanism by which TRPV1-dependent nociception and pain can be regulated.}, } @article {pmid29378957, year = {2018}, author = {Kwon, Y and Shen, J and Lee, MH and Geem, KR and Jiang, L and Hwang, I}, title = {AtCAP2 is crucial for lytic vacuole biogenesis during germination by positively regulating vacuolar protein trafficking.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1675-E1683}, pmid = {29378957}, issn = {1091-6490}, mesh = {Arabidopsis/genetics/growth & development/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Germination ; Microtubule-Associated Proteins/genetics/*metabolism ; Organelle Biogenesis ; Protein Transport ; Seeds/genetics/*growth & development/metabolism ; Vacuoles/genetics/*metabolism ; }, abstract = {Protein trafficking is a fundamental mechanism of subcellular organization and contributes to organellar biogenesis. AtCAP2 is an Arabidopsis homolog of the Mesembryanthemum crystallinum calcium-dependent protein kinase 1 adaptor protein 2 (McCAP2), a member of the syntaxin superfamily. Here, we show that AtCAP2 plays an important role in the conversion to the lytic vacuole (LV) during early plant development. The AtCAP2 loss-of-function mutant atcap2-1 displayed delays in protein storage vacuole (PSV) protein degradation, PSV fusion, LV acidification, and biosynthesis of several vacuolar proteins during germination. At the mature stage, atcap2-1 plants accumulated vacuolar proteins in the prevacuolar compartment (PVC) instead of the LV. In wild-type plants, AtCAP2 localizes to the PVC as a peripheral membrane protein and in the PVC compartment recruits glyceraldehyde-3-phosphate dehydrogenase C2 (GAPC2) to the PVC. We propose that AtCAP2 contributes to LV biogenesis during early plant development by supporting the trafficking of specific proteins involved in the PSV-to-LV transition and LV acidification during early stages of plant development.}, } @article {pmid29378956, year = {2018}, author = {Gupta, D and Lin, B and Cowan, A and Heinen, CD}, title = {ATR-Chk1 activation mitigates replication stress caused by mismatch repair-dependent processing of DNA damage.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1523-1528}, pmid = {29378956}, issn = {1091-6490}, support = {R01 CA115783/CA/NCI NIH HHS/United States ; }, mesh = {Apoptosis/drug effects ; Ataxia Telangiectasia Mutated Proteins/genetics/metabolism ; Checkpoint Kinase 1/genetics/*metabolism ; DNA Damage/*physiology ; DNA Mismatch Repair/*physiology ; DNA Replication ; Embryonic Stem Cells/drug effects/physiology ; Enzyme Activation ; HeLa Cells ; Humans ; Methylnitronitrosoguanidine/pharmacology ; MutS Homolog 2 Protein/genetics/metabolism ; S Phase/physiology ; }, abstract = {The mismatch repair pathway (MMR) is essential for removing DNA polymerase errors, thereby maintaining genomic stability. Loss of MMR function increases mutation frequency and is associated with tumorigenesis. However, how MMR is executed at active DNA replication forks is unclear. This has important implications for understanding how MMR repairs O6-methylguanine/thymidine (MeG/T) mismatches created upon exposure to DNA alkylating agents. If MeG/T lesion recognition by MMR initiates mismatch excision, the reinsertion of a mismatched thymidine during resynthesis could initiate futile repair cycles. One consequence of futile repair cycles might be a disruption of overall DNA replication in the affected cell. Herein, we show that in MMR-proficient HeLa cancer cells, treatment with a DNA alkylating agent slows S phase progression, yet cells still progress into the next cell cycle. In the first S phase following treatment, they activate ataxia telangiectasia and Rad3-related (ATR)-Checkpoint Kinase 1 (Chk1) signaling, which limits DNA damage, while inhibition of ATR kinase activity accelerates DNA damage accumulation and sensitivity to the DNA alkylating agent. We also observed that exposure of human embryonic stem cells to alkylation damage severely compromised DNA replication in a MMR-dependent manner. These cells fail to activate the ATR-Chk1 signaling axis, which may limit their ability to handle replication stress. Accordingly, they accumulate double-strand breaks and undergo immediate apoptosis. Our findings implicate the MMR-directed response to alkylation damage as a replication stress inducer, suggesting that repeated MMR processing of mismatches may occur that can disrupt S phase progression.}, } @article {pmid29378955, year = {2018}, author = {Fernández-Moncada, I and Ruminot, I and Robles-Maldonado, D and Alegría, K and Deitmer, JW and Barros, LF}, title = {Neuronal control of astrocytic respiration through a variant of the Crabtree effect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1623-1628}, pmid = {29378955}, issn = {1091-6490}, mesh = {Animals ; Astrocytes/cytology/*physiology ; Cells, Cultured ; Energy Metabolism ; Glycolysis/*physiology ; Hippocampus/cytology/*physiology ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Inbred CBA ; Mice, Knockout ; Mitochondria/*physiology ; Neurons/cytology/*physiology ; *Oxygen Consumption ; Sodium-Bicarbonate Symporters/physiology ; }, abstract = {Aerobic glycolysis is a phenomenon that in the long term contributes to synaptic formation and growth, is reduced by normal aging, and correlates with amyloid beta deposition. Aerobic glycolysis starts within seconds of neural activity and it is not obvious why energetic efficiency should be compromised precisely when energy demand is highest. Using genetically encoded FRET nanosensors and real-time oxygen measurements in culture and in hippocampal slices, we show here that astrocytes respond to physiological extracellular K+ with an acute rise in cytosolic ATP and a parallel inhibition of oxygen consumption, explained by glycolytic stimulation via the Na+-bicarbonate cotransporter NBCe1. This control of mitochondrial respiration via glycolysis modulation is reminiscent of a phenomenon previously described in proliferating cells, known as the Crabtree effect. Fast brain aerobic glycolysis may be interpreted as a strategy whereby neurons manipulate neighboring astrocytes to obtain oxygen, thus maximizing information processing.}, } @article {pmid29378954, year = {2018}, author = {Gernat, T and Rao, VD and Middendorf, M and Dankowicz, H and Goldenfeld, N and Robinson, GE}, title = {Automated monitoring of behavior reveals bursty interaction patterns and rapid spreading dynamics in honeybee social networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1433-1438}, pmid = {29378954}, issn = {1091-6490}, support = {R01 GM117467/GM/NIGMS NIH HHS/United States ; }, mesh = {*Animal Communication ; Animals ; Bees/*physiology ; Models, Biological ; *Social Behavior ; }, abstract = {Social networks mediate the spread of information and disease. The dynamics of spreading depends, among other factors, on the distribution of times between successive contacts in the network. Heavy-tailed (bursty) time distributions are characteristic of human communication networks, including face-to-face contacts and electronic communication via mobile phone calls, email, and internet communities. Burstiness has been cited as a possible cause for slow spreading in these networks relative to a randomized reference network. However, it is not known whether burstiness is an epiphenomenon of human-specific patterns of communication. Moreover, theory predicts that fast, bursty communication networks should also exist. Here, we present a high-throughput technology for automated monitoring of social interactions of individual honeybees and the analysis of a rich and detailed dataset consisting of more than 1.2 million interactions in five honeybee colonies. We find that bees, like humans, also interact in bursts but that spreading is significantly faster than in a randomized reference network and remains so even after an experimental demographic perturbation. Thus, while burstiness may be an intrinsic property of social interactions, it does not always inhibit spreading in real-world communication networks. We anticipate that these results will inform future models of large-scale social organization and information and disease transmission, and may impact health management of threatened honeybee populations.}, } @article {pmid29378953, year = {2018}, author = {Feng, D and Notbohm, J and Benjamin, A and He, S and Wang, M and Ang, LH and Bantawa, M and Bouzid, M and Del Gado, E and Krishnan, R and Pollak, MR}, title = {Disease-causing mutation in α-actinin-4 promotes podocyte detachment through maladaptation to periodic stretch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1517-1522}, pmid = {29378953}, issn = {1091-6490}, support = {R01 DK059588/DK/NIDDK NIH HHS/United States ; R37 DK059588/DK/NIDDK NIH HHS/United States ; T32 DK007199/DK/NIDDK NIH HHS/United States ; P30 DK079337/DK/NIDDK NIH HHS/United States ; T32 DK007527/DK/NIDDK NIH HHS/United States ; }, mesh = {Actinin/*genetics/metabolism ; Animals ; Cell Adhesion ; Cytoskeleton/metabolism ; Female ; Glomerulosclerosis, Focal Segmental/genetics/pathology ; Humans ; Male ; Mice, Transgenic ; Podocytes/*pathology ; *Point Mutation ; }, abstract = {α-Actinin-4 (ACTN4) bundles and cross-links actin filaments to confer mechanical resilience to the reconstituted actin network. How this resilience is built and dynamically regulated in the podocyte, and the cause of its failure in ACTN4 mutation-associated focal segmental glomerulosclerosis (FSGS), remains poorly defined. Using primary podocytes isolated from wild-type (WT) and FSGS-causing point mutant Actn4 knockin mice, we report responses to periodic stretch. While WT cells largely maintained their F-actin cytoskeleton and contraction, mutant cells developed extensive and irrecoverable reductions in these same properties. This difference was attributable to both actin material changes and a more spatially correlated intracellular stress in mutant cells. When stretched cells were further challenged using a cell adhesion assay, mutant cells were more likely to detach. Together, these data suggest a mechanism for mutant podocyte dysfunction and loss in FSGS-it is a direct consequence of mechanical responses of a cytoskeleton that is brittle.}, } @article {pmid29378952, year = {2018}, author = {Marchetti, C and Swartzwelter, B and Gamboni, F and Neff, CP and Richter, K and Azam, T and Carta, S and Tengesdal, I and Nemkov, T and D'Alessandro, A and Henry, C and Jones, GS and Goodrich, SA and St Laurent, JP and Jones, TM and Scribner, CL and Barrow, RB and Altman, RD and Skouras, DB and Gattorno, M and Grau, V and Janciauskiene, S and Rubartelli, A and Joosten, LAB and Dinarello, CA}, title = {OLT1177, a β-sulfonyl nitrile compound, safe in humans, inhibits the NLRP3 inflammasome and reverses the metabolic cost of inflammation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1530-E1539}, pmid = {29378952}, issn = {1091-6490}, support = {R01 AI015614/AI/NIAID NIH HHS/United States ; R56 AI015614/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Anti-Inflammatory Agents/chemistry/*pharmacology/therapeutic use ; Caspase 1/metabolism ; Cells, Cultured ; Humans ; Inflammasomes/*antagonists & inhibitors ; Inflammation/chemically induced/immunology/*prevention & control ; Interleukin-18/metabolism ; Interleukin-1beta/metabolism ; Lipopolysaccharides/toxicity ; Macrophages/*drug effects/metabolism/pathology ; Male ; Mice ; Mice, Inbred C57BL ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics/*metabolism ; Nitriles/chemistry/*pharmacology/therapeutic use ; }, abstract = {Activation of the NLRP3 inflammasome induces maturation of IL-1β and IL-18, both validated targets for treating acute and chronic inflammatory diseases. Here, we demonstrate that OLT1177, an orally active β-sulfonyl nitrile molecule, inhibits activation of the NLRP3 inflammasome. In vitro, nanomolar concentrations of OLT1177 reduced IL-1β and IL-18 release following canonical and noncanonical NLRP3 inflammasome activation. The molecule showed no effect on the NLRC4 and AIM2 inflammasomes, suggesting specificity for NLRP3. In LPS-stimulated human blood-derived macrophages, OLT1177 decreased IL-1β levels by 60% and IL-18 by 70% at concentrations 100-fold lower in vitro than plasma concentrations safely reached in humans. OLT1177 also reduced IL-1β release and caspase-1 activity in freshly obtained human blood neutrophils. In monocytes isolated from patients with cryopyrin-associated periodic syndrome (CAPS), OLT1177 inhibited LPS-induced IL-1β release by 84% and 36%. Immunoprecipitation and FRET analysis demonstrated that OLT1177 prevented NLRP3-ASC, as well as NLRP3-caspase-1 interaction, thus inhibiting NLRP3 inflammasome oligomerization. In a cell-free assay, OLT1177 reduced ATPase activity of recombinant NLRP3, suggesting direct targeting of NLRP3. Mechanistically, OLT1177 did not affect potassium efflux, gene expression, or synthesis of the IL-1β precursor. Steady-state levels of phosphorylated NF-κB and IkB kinase were significantly lowered in spleen cells from OLT1177-treated mice. We observed reduced IL-1β content in tissue homogenates, limited oxidative stress, and increased muscle oxidative metabolism in OLT1177-treated mice challenged with LPS. Healthy humans receiving 1,000 mg of OLT1177 daily for 8 d exhibited neither adverse effects nor biochemical or hematological changes.}, } @article {pmid29378951, year = {2018}, author = {Song, E and Ramos, SV and Huang, X and Liu, Y and Botta, A and Sung, HK and Turnbull, PC and Wheeler, MB and Berger, T and Wilson, DJ and Perry, CGR and Mak, TW and Sweeney, G}, title = {Holo-lipocalin-2-derived siderophores increase mitochondrial ROS and impair oxidative phosphorylation in rat cardiomyocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1576-1581}, pmid = {29378951}, issn = {1091-6490}, support = {FDN-143219//CIHR/Canada ; }, mesh = {Animals ; Gentisates/pharmacology ; Hydroxybenzoates/pharmacology ; Iron/metabolism ; Lipocalin-2/*physiology ; Male ; Mice ; Mice, Knockout ; Mitochondria/drug effects/metabolism/*pathology ; Myocytes, Cardiac/drug effects/metabolism/*pathology ; Oxidative Phosphorylation ; Rats ; Rats, Wistar ; Reactive Oxygen Species/*metabolism ; Reperfusion Injury/drug therapy/metabolism/*pathology ; Siderophores/*metabolism ; }, abstract = {Lipocalin-2 (Lcn2), a critical component of the innate immune response which binds siderophores and limits bacterial iron acquisition, can elicit spillover adverse proinflammatory effects. Here we show that holo-Lcn2 (Lcn2-siderophore-iron, 1:3:1) increases mitochondrial reactive oxygen species (ROS) generation and attenuates mitochondrial oxidative phosphorylation in adult rat primary cardiomyocytes in a manner blocked by N-acetyl-cysteine or the mitochondria-specific antioxidant SkQ1. We further demonstrate using siderophores 2,3-DHBA (2,3-dihydroxybenzoic acid) and 2,5-DHBA that increased ROS and reduction in oxidative phosphorylation are direct effects of the siderophore component of holo-Lcn2 and not due to apo-Lcn2 alone. Extracellular apo-Lcn2 enhanced the potency of 2,3-DHBA and 2,5-DHBA to increase ROS production and decrease mitochondrial respiratory capacity, whereas intracellular apo-Lcn2 attenuated these effects. These actions of holo-Lcn2 required an intact plasma membrane and were decreased by inhibition of endocytosis. The hearts, but not serum, of Lcn2 knockout (LKO) mice contained lower levels of 2,5-DHBA compared with wild-type hearts. Furthermore, LKO mice were protected from ischemia/reperfusion-induced cardiac mitochondrial dysfunction. Our study identifies the siderophore moiety of holo-Lcn2 as a regulator of cardiomyocyte mitochondrial bioenergetics.}, } @article {pmid29378950, year = {2018}, author = {Ohtake, F and Tsuchiya, H and Saeki, Y and Tanaka, K}, title = {K63 ubiquitylation triggers proteasomal degradation by seeding branched ubiquitin chains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1401-E1408}, pmid = {29378950}, issn = {1091-6490}, mesh = {Carrier Proteins/*metabolism ; HeLa Cells ; Humans ; Lysine/*metabolism ; Polyubiquitin/*metabolism ; Proteasome Endopeptidase Complex/*metabolism ; Proteolysis ; Repressor Proteins/*metabolism ; Signal Transduction ; Ubiquitin-Protein Ligases/*metabolism ; *Ubiquitination ; }, abstract = {Different polyubiquitin chain linkages direct substrates toward distinct cellular pathways. K63-linked ubiquitylation is known to regulate proteasome-independent events such as signal transduction, but its function in the context of heterogeneous ubiquitin chains remains unclear. Here, we report that K63 ubiquitylation plays a critical role in proteasome-mediated substrate degradation by serving as a "seed" for K48/K63 branched ubiquitin chains. Quantitative analysis revealed that K48/K63 branched linkages preferentially associate with proteasomes in cells. We found that ITCH-dependent K63 ubiquitylation of the proapoptotic regulator TXNIP triggered subsequent assembly of K48/K63 branched chains by recruiting ubiquitin-interacting ligases such as UBR5, leading to TXNIP degradation. These results reveal a role for K63 chains as a substrate-specific mark for proteasomal degradation involved in regulating cell fate. Our findings provide insight into how cellular interpretation of the ubiquitin code is altered by combinations of ubiquitin linkages.}, } @article {pmid29378949, year = {2018}, author = {Finotello, A and Lanzoni, S and Ghinassi, M and Marani, M and Rinaldo, A and D'Alpaos, A}, title = {Field migration rates of tidal meanders recapitulate fluvial morphodynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1463-1468}, pmid = {29378949}, issn = {1091-6490}, abstract = {The majority of tidal channels display marked meandering features. Despite their importance in oil-reservoir formation and tidal landscape morphology, questions remain on whether tidal-meander dynamics could be understood in terms of fluvial processes and theory. Key differences suggest otherwise, like the periodic reversal of landscape-forming tidal flows and the widely accepted empirical notion that tidal meanders are stable landscape features, in stark contrast with their migrating fluvial counterparts. On the contrary, here we show that, once properly normalized, observed migration rates of tidal and fluvial meanders are remarkably similar. Key to normalization is the role of tidal channel width that responds to the strong spatial gradients of landscape-forming flow rates and tidal prisms. We find that migration dynamics of tidal meanders agree with nonlinear theories for river meander evolution. Our results challenge the conventional view of tidal channels as stable landscape features and suggest that meandering tidal channels recapitulate many fluvial counterparts owing to large gradients of tidal prisms across meander wavelengths.}, } @article {pmid29378948, year = {2018}, author = {Xiang, S and Gu, H and Jin, L and Thorne, RF and Zhang, XD and Wu, M}, title = {LncRNA IDH1-AS1 links the functions of c-Myc and HIF1α via IDH1 to regulate the Warburg effect.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1465-E1474}, pmid = {29378948}, issn = {1091-6490}, mesh = {Animals ; Cell Proliferation ; Female ; Glycolysis/*physiology ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Isocitrate Dehydrogenase/antagonists & inhibitors/genetics/*metabolism ; Ketoglutaric Acids/metabolism ; Mice ; Mice, Nude ; Proto-Oncogene Proteins c-myc/genetics/*metabolism ; RNA, Antisense/*genetics ; RNA, Long Noncoding/*genetics ; Transcriptional Activation ; Tumor Cells, Cultured ; Uterine Cervical Neoplasms/genetics/pathology/*prevention & control ; Xenograft Model Antitumor Assays ; }, abstract = {The oncoprotein c-Myc plays an important role in regulating glycolysis under normoxia; yet, in cancer cells, HIF1α, which is essential for driving glycolysis under hypoxia, is often up-regulated even in the presence of oxygen. The relationship between these two major regulators of the Warburg effect remains to be fully defined. Here we demonstrate that regulation of a long noncoding RNA (lncRNA), named IDH1-AS1, enables c-Myc to collaborate with HIF1α in activating the Warburg effect under normoxia. c-Myc transcriptionally repressed IDH1-AS1, which, upon expression, promoted homodimerization of IDH1 and thus enhanced its enzymatic activity. This resulted in increased α-KG and decreased ROS production and subsequent HIF1α down-regulation, leading to attenuation of glycolysis. Hence, c-Myc repression of IDH1-AS1 promotes activation of the Warburg effect by HIF1α. As such, IDH1-AS1 overexpression inhibited cell proliferation, whereas silencing of IDH1-AS1 promoted cell proliferation and cancer xenograft growth. Restoring IDH1-AS1 expression may therefore represent a potential metabolic approach for cancer treatment.}, } @article {pmid29378947, year = {2018}, author = {Triemer, T and Messikommer, A and Glasauer, SMK and Alzeer, J and Paulisch, MH and Luedtke, NW}, title = {Superresolution imaging of individual replication forks reveals unexpected prodrug resistance mechanism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1366-E1373}, pmid = {29378947}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*chemistry/pharmacology ; Azides/*chemistry/pharmacology ; Cell Cycle ; Cytarabine/*chemistry/pharmacology ; DNA/*chemistry ; *DNA Replication ; Humans ; Prodrugs/*chemistry/pharmacology ; Proliferating Cell Nuclear Antigen/metabolism ; Uridine/*analogs & derivatives/chemistry/pharmacology ; Zebrafish/*growth & development ; }, abstract = {Many drugs require extensive metabolism en route to their targets. High-resolution visualization of prodrug metabolism should therefore utilize analogs containing a small modification that does not interfere with its metabolism or mode of action. In addition to serving as mechanistic probes, such analogs provide candidates for theranostics when applied in both therapeutic and diagnostic modalities. Here a traceable mimic of the widely used anticancer prodrug cytarabine (ara-C) was generated by converting a single hydroxyl group to azide, giving "AzC." This compound exhibited the same biological profile as ara-C in cell cultures and zebrafish larvae. Using azide-alkyne "click" reactions, we uncovered an apparent contradiction: drug-resistant cells incorporated relatively large quantities of AzC into their genomes and entered S-phase arrest, whereas drug-sensitive cells incorporated only small quantities of AzC. Fluorescence microscopy was used to elucidate structural features associated with drug resistance by characterizing the architectures of stalled DNA replication foci containing AzC, EdU, γH2AX, and proliferating cell nuclear antigen (PCNA). Three-color superresolution imaging revealed replication foci containing one, two, or three partially resolved replication forks. Upon removing AzC from the media, resumption of DNA synthesis and completion of the cell cycle occurred before complete removal of AzC from genomes in vitro and in vivo. These results revealed an important mechanism for the low toxicity of ara-C toward normal tissues and drug-resistant cancer cells, where its efficient incorporation into DNA gives rise to highly stable, stalled replication forks that limit further incorporation of the drug, yet allow for the resumption of DNA synthesis and cellular division following treatment.}, } @article {pmid29378946, year = {2018}, author = {Garton, M and Nim, S and Stone, TA and Wang, KE and Deber, CM and Kim, PM}, title = {Method to generate highly stable D-amino acid analogs of bioactive helical peptides using a mirror image of the entire PDB.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1505-1510}, pmid = {29378946}, issn = {1091-6490}, support = {MOP-123526//CIHR/Canada ; PJT-153279//CIHR/Canada ; }, mesh = {Algorithms ; Amino Acids/*chemistry ; *Databases, Protein ; Glucagon-Like Peptide 1/agonists/chemistry/metabolism ; Glucagon-Like Peptide-1 Receptor/metabolism ; HEK293 Cells ; Half-Life ; Humans ; Parathyroid Hormone/agonists/chemistry/metabolism ; Peptides/*chemistry/metabolism/pharmacokinetics ; Protein Conformation ; Protein Engineering/*methods ; Receptor, Parathyroid Hormone, Type 1/metabolism ; Reproducibility of Results ; }, abstract = {Biologics are a rapidly growing class of therapeutics with many advantages over traditional small molecule drugs. A major obstacle to their development is that proteins and peptides are easily destroyed by proteases and, thus, typically have prohibitively short half-lives in human gut, plasma, and cells. One of the most effective ways to prevent degradation is to engineer analogs from dextrorotary (D)-amino acids, with up to 105-fold improvements in potency reported. We here propose a general peptide-engineering platform that overcomes limitations of previous methods. By creating a mirror image of every structure in the Protein Data Bank (PDB), we generate a database of ∼2.8 million D-peptides. To obtain a D-analog of a given peptide, we search the (D)-PDB for similar configurations of its critical-"hotspot"-residues. As a proof of concept, we apply our method to two peptides that are Food and Drug Administration approved as therapeutics for diabetes and osteoporosis, respectively. We obtain D-analogs that activate the GLP1 and PTH1 receptors with the same efficacy as their natural counterparts and show greatly increased half-life.}, } @article {pmid29378945, year = {2018}, author = {Matamouros, S and Hayden, HS and Hager, KR and Brittnacher, MJ and Lachance, K and Weiss, EJ and Pope, CE and Imhaus, AF and McNally, CP and Borenstein, E and Hoffman, LR and Miller, SI}, title = {Adaptation of commensal proliferating Escherichia coli to the intestinal tract of young children with cystic fibrosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1605-1610}, pmid = {29378945}, issn = {1091-6490}, support = {P30 DK089507/DK/NIDDK NIH HHS/United States ; R01 DK095869/DK/NIDDK NIH HHS/United States ; }, mesh = {Case-Control Studies ; Child, Preschool ; Cystic Fibrosis/genetics/*microbiology/pathology ; Dietary Fats/metabolism ; Escherichia coli/*pathogenicity ; Escherichia coli Infections/genetics/*microbiology/pathology ; Feces/*microbiology ; Gastrointestinal Microbiome/*genetics ; Gene Regulatory Networks ; Glycerol/metabolism ; Humans ; Infant ; Intestines/*microbiology ; Phospholipids/metabolism ; Phylogeny ; United States ; }, abstract = {The mature human gut microbiota is established during the first years of life, and altered intestinal microbiomes have been associated with several human health disorders. Escherichia coli usually represents less than 1% of the human intestinal microbiome, whereas in cystic fibrosis (CF), greater than 50% relative abundance is common and correlates with intestinal inflammation and fecal fat malabsorption. Despite the proliferation of E. coli and other Proteobacteria in conditions involving chronic gastrointestinal tract inflammation, little is known about adaptation of specific characteristics associated with microbiota clonal expansion. We show that E. coli isolated from fecal samples of young children with CF has adapted to growth on glycerol, a major component of fecal fat. E. coli isolates from different CF patients demonstrate an increased growth rate in the presence of glycerol compared with E. coli from healthy controls, and unrelated CF E. coli strains have independently acquired this growth trait. Furthermore, CF and control E. coli isolates have differential gene expression when grown in minimal media with glycerol as the sole carbon source. While CF isolates display a growth-promoting transcriptional profile, control isolates engage stress and stationary-phase programs, which likely results in slower growth rates. Our results indicate that there is selection of unique characteristics within the microbiome of individuals with CF, which could contribute to individual disease outcomes.}, } @article {pmid29378944, year = {2018}, author = {Tian, W and Lin, M and Tang, K and Liang, J and Naveed, H}, title = {High-resolution structure prediction of β-barrel membrane proteins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1511-1516}, pmid = {29378944}, issn = {1091-6490}, support = {R01 CA204962/CA/NCI NIH HHS/United States ; R01 GM079804/GM/NIGMS NIH HHS/United States ; R01 GM126558/GM/NIGMS NIH HHS/United States ; R21 AI126308/AI/NIAID NIH HHS/United States ; }, mesh = {Fimbriae Proteins/chemistry ; Membrane Proteins/*chemistry ; *Models, Molecular ; Protein Conformation, beta-Strand ; Protein Domains ; Voltage-Dependent Anion Channels/chemistry ; }, abstract = {[Formula: see text]-Barrel membrane proteins ([Formula: see text]MPs) play important roles, but knowledge of their structures is limited. We have developed a method to predict their 3D structures. We predict strand registers and construct transmembrane (TM) domains of [Formula: see text]MPs accurately, including proteins for which no prediction has been attempted before. Our method also accurately predicts structures from protein families with a limited number of sequences and proteins with novel folds. An average main-chain rmsd of 3.48 Å is achieved between predicted and experimentally resolved structures of TM domains, which is a significant improvement ([Formula: see text]3 Å) over a recent study. For [Formula: see text]MPs with NMR structures, the deviation between predictions and experimentally solved structures is similar to the difference among the NMR structures, indicating excellent prediction accuracy. Moreover, we can now accurately model the extended [Formula: see text]-barrels and loops in non-TM domains, increasing the overall coverage of structure prediction by [Formula: see text]%. Our method is general and can be applied to genome-wide structural prediction of [Formula: see text]MPs.}, } @article {pmid29378943, year = {2018}, author = {Lee, HW and Park, SH and Weng, MW and Wang, HT and Huang, WC and Lepor, H and Wu, XR and Chen, LC and Tang, MS}, title = {E-cigarette smoke damages DNA and reduces repair activity in mouse lung, heart, and bladder as well as in human lung and bladder cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1560-E1569}, pmid = {29378943}, issn = {1091-6490}, support = {P01 CA165980/CA/NCI NIH HHS/United States ; P30 CA016087/CA/NCI NIH HHS/United States ; P30 ES000260/ES/NIEHS NIH HHS/United States ; R01 CA190678/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinogenesis/drug effects ; Cell Line ; DNA Damage/*drug effects ; DNA Repair/*drug effects ; Electronic Nicotine Delivery Systems ; Heart/*drug effects ; Humans ; Lung/*drug effects/metabolism ; Male ; Mice ; Mutation/drug effects ; Nicotine/chemistry/*toxicity ; Nitrosamines/chemistry/*toxicity ; Smoke/*adverse effects ; Urinary Bladder/*drug effects/metabolism ; }, abstract = {E-cigarette smoke delivers stimulant nicotine as aerosol without tobacco or the burning process. It contains neither carcinogenic incomplete combustion byproducts nor tobacco nitrosamines, the nicotine nitrosation products. E-cigarettes are promoted as safe and have gained significant popularity. In this study, instead of detecting nitrosamines, we directly measured DNA damage induced by nitrosamines in different organs of E-cigarette smoke-exposed mice. We found mutagenic O6-methyldeoxyguanosines and γ-hydroxy-1,N2 -propano-deoxyguanosines in the lung, bladder, and heart. DNA-repair activity and repair proteins XPC and OGG1/2 are significantly reduced in the lung. We found that nicotine and its metabolite, nicotine-derived nitrosamine ketone, can induce the same effects and enhance mutational susceptibility and tumorigenic transformation of cultured human bronchial epithelial and urothelial cells. These results indicate that nicotine nitrosation occurs in vivo in mice and that E-cigarette smoke is carcinogenic to the murine lung and bladder and harmful to the murine heart. It is therefore possible that E-cigarette smoke may contribute to lung and bladder cancer, as well as heart disease, in humans.}, } @article {pmid29378942, year = {2018}, author = {Russi, AE and Ebel, ME and Yang, Y and Brown, MA}, title = {Male-specific IL-33 expression regulates sex-dimorphic EAE susceptibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1520-E1529}, pmid = {29378942}, issn = {1091-6490}, support = {F31 NS084691/NS/NINDS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; R21 NS081598/NS/NINDS NIH HHS/United States ; S10 OD011996/OD/NIH HHS/United States ; }, mesh = {Animals ; Cytokines/metabolism ; Encephalomyelitis, Autoimmune, Experimental/*etiology/*pathology ; Female ; Interleukin-33/genetics/immunology/*metabolism ; Male ; Mast Cells/*immunology/metabolism ; Mice ; Mice, Inbred C57BL ; *Sex Characteristics ; Testosterone/blood ; Th17 Cells/*immunology ; }, abstract = {The cellular and molecular basis of sex-dimorphic autoimmune diseases, such as the CNS demyelinating disease multiple sclerosis (MS), remains unclear. Our studies in the SJL mouse model of MS, experimental autoimmune encephalomyelitis (EAE), reveal that sex-determined differences in Il33 expression by innate immune cells in response to myelin peptide immunization regulate EAE susceptibility. IL-33 is selectively induced in PLP139-151-immunized males and activates type 2 innate lymphoid cells (ILC2s), cells that promote and sustain a nonpathogenic Th2 myelin-specific response. Without this attenuating IL-33 response, females generate an encephalitogenic Th17-dominant response, which can be reversed by IL-33 treatment. Mast cells are one source of IL-33 and we provide evidence that testosterone directly induces Il33 gene expression and also exerts effects on the potential for Il33 gene expression during mast cell development. Thus, in contrast to their pathogenic role in allergy, we propose a sex-specific role for both mast cells and ILC2s as attenuators of the pathogenic Th response in CNS inflammatory disease.}, } @article {pmid29378941, year = {2018}, author = {Bansal, A and Yang, F and Xi, T and Zhang, Y and Ho, JS}, title = {In vivo wireless photonic photodynamic therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1469-1474}, pmid = {29378941}, issn = {1091-6490}, mesh = {Animals ; Dose-Response Relationship, Drug ; Electric Power Supplies ; Equipment Design ; Implants, Experimental ; Mice, Inbred C57BL ; Miniaturization ; Neovascularization, Pathologic ; Photochemotherapy/instrumentation/*methods ; Photosensitizing Agents/administration & dosage/*pharmacokinetics ; Porphyrins/administration & dosage/pharmacokinetics ; Urinary Bladder Neoplasms/blood supply/*drug therapy/pathology ; Wireless Technology/*instrumentation ; Xenograft Model Antitumor Assays ; }, abstract = {An emerging class of targeted therapy relies on light as a spatially and temporally precise stimulus. Photodynamic therapy (PDT) is a clinical example in which optical illumination selectively activates light-sensitive drugs, termed photosensitizers, destroying malignant cells without the side effects associated with systemic treatments such as chemotherapy. Effective clinical application of PDT and other light-based therapies, however, is hindered by challenges in light delivery across biological tissue, which is optically opaque. To target deep regions, current clinical PDT uses optical fibers, but their incompatibility with chronic implantation allows only a single dose of light to be delivered per surgery. Here we report a wireless photonic approach to PDT using a miniaturized (30 mg, 15 mm3) implantable device and wireless powering system for light delivery. We demonstrate the therapeutic efficacy of this approach by activating photosensitizers (chlorin e6) through thick (>3 cm) tissues inaccessible by direct illumination, and by delivering multiple controlled doses of light to suppress tumor growth in vivo in animal cancer models. This versatility in light delivery overcomes key clinical limitations in PDT, and may afford further opportunities for light-based therapies.}, } @article {pmid29378940, year = {2018}, author = {Suzuki, TN}, title = {Alarm calls evoke a visual search image of a predator in birds.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1541-1545}, pmid = {29378940}, issn = {1091-6490}, mesh = {Animals ; Auditory Perception/*physiology ; Behavior, Animal/*physiology ; Birds ; Fear/*physiology ; Pattern Recognition, Visual/*physiology ; Predatory Behavior/*physiology ; Snakes ; Visual Fields/*physiology ; *Vocalization, Animal ; }, abstract = {One of the core features of human speech is that words cause listeners to retrieve corresponding visual mental images. However, whether vocalizations similarly evoke mental images in animal communication systems is surprisingly unknown. Japanese tits (Parus minor) produce specific alarm calls when and only when encountering a predatory snake. Here, I show that simply hearing these calls causes tits to become more visually perceptive to objects resembling snakes. During playback of snake-specific alarm calls, tits approach a wooden stick being moved in a snake-like fashion. However, tits do not respond to the same stick when hearing other call types or if the stick's movement is dissimilar to that of a snake. Thus, before detecting a real snake, tits retrieve its visual image from snake-specific alarm calls and use this to search out snakes. This study provides evidence for a call-evoked visual search image in a nonhuman animal, offering a paradigm to explore the cognitive basis for animal vocal communication in the wild.}, } @article {pmid29378939, year = {2018}, author = {Rumpf, SB and Hülber, K and Klonner, G and Moser, D and Schütz, M and Wessely, J and Willner, W and Zimmermann, NE and Dullinger, S}, title = {Range dynamics of mountain plants decrease with elevation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1848-1853}, pmid = {29378939}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; *Altitude ; Demography ; *Ecosystem ; Plant Physiological Phenomena ; Plants/*classification ; Temperature ; }, abstract = {Many studies report that mountain plant species are shifting upward in elevation. However, the majority of these reports focus on shifts of upper limits. Here, we expand the focus and simultaneously analyze changes of both range limits, optima, and abundances of 183 mountain plant species. We therefore resurveyed 1,576 vegetation plots first recorded before 1970 in the European Alps. We found that both range limits and optima shifted upward in elevation, but the most pronounced trend was a mean increase in species abundance. Despite huge species-specific variation, range dynamics showed a consistent trend along the elevational gradient: Both range limits and optima shifted upslope faster the lower they were situated historically, and species' abundance increased more for species from lower elevations. Traits affecting the species' dispersal and persistence capacity were not related to their range dynamics. Using indicator values to stratify species by their thermal and nutrient demands revealed that elevational ranges of thermophilic species tended to expand, while those of cold-adapted species tended to contract. Abundance increases were strongest for nutriphilous species. These results suggest that recent climate warming interacted with airborne nitrogen deposition in driving the observed dynamics. So far, the majority of species appear as "winners" of recent changes, yet "losers" are overrepresented among high-elevation, cold-adapted species with low nutrient demands. In the decades to come, high-alpine species may hence face the double pressure of climatic changes and novel, superior competitors that move up faster than they themselves can escape to even higher elevations.}, } @article {pmid29378938, year = {2018}, author = {Verma, AA and Jimenez, MP and Tangermann, RH and Subramanian, SV and Razak, F}, title = {Insecurity, polio vaccination rates, and polio incidence in northwest Pakistan.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1593-1598}, pmid = {29378938}, issn = {1091-6490}, support = {T32 HD007338/HD/NICHD NIH HHS/United States ; }, mesh = {*Disease Eradication ; Humans ; Incidence ; Pakistan/epidemiology ; Poliomyelitis/*epidemiology/*prevention & control/virology ; Poliovirus ; *Population Surveillance ; Risk Factors ; Security Measures/*statistics & numerical data ; *Vaccination ; }, abstract = {Pakistan is one of three countries in which endemic transmission of poliovirus has never been stopped. Insecurity is often cited but poorly studied as a barrier to eradicating polio. We analyzed routinely collected health data from 32 districts of northwest Pakistan and constructed an index of insecurity based on journalistic reports of the monthly number of deaths and injuries resulting from conflict-related security incidents. The primary outcomes were the monthly incidence of paralytic polio cases within each district between 2007 and 2014 and the polio vaccination percentage from 666 district-level vaccination campaigns between 2007 and 2009, targeting ∼5.7 million children. Multilevel Poisson regression controlling for time and district fixed effects was used to model the association between insecurity, vaccinator access, vaccination rates, and polio incidence. The number of children inaccessible to vaccinators was 19.7% greater (95% CI: 19.2-20.2%), and vaccination rates were 5.3% lower (95% CI: 5.2-5.3%) in "high-insecurity" campaigns compared with "secure" campaigns. The unadjusted mean vaccination rate was 96.3% (SD = 8.6) in secure campaigns and 88.3% (SD = 19.2) in high-insecurity campaigns. Polio incidence was 73.0% greater (95% CI: 30-131%) during high-insecurity months (unadjusted mean = 0.13 cases per million people, SD = 0.71) compared with secure months (unadjusted mean = 1.23 cases per million people, SD = 4.28). Thus, insecurity was associated with reduced vaccinator access, reduced polio vaccination, and increased polio incidence in northwest Pakistan. These findings demonstrate that insecurity is an important obstacle to global polio eradication.}, } @article {pmid29378937, year = {2018}, author = {Dong, X and Zhao, B and Lin, FY and Lu, C and Rogers, BN and Springer, TA}, title = {High integrin αVβ6 affinity reached by hybrid domain deletion slows ligand-binding on-rate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1429-E1436}, pmid = {29378937}, issn = {1091-6490}, support = {R01 AR067288/AR/NIAMS NIH HHS/United States ; }, mesh = {Antigens, Neoplasm/chemistry/genetics/*metabolism ; Binding Sites ; Cytoskeleton/*metabolism ; Humans ; Integrins/chemistry/genetics/*metabolism ; Ligands ; Manganese/metabolism ; Models, Molecular ; Protein Binding ; *Protein Conformation ; Sequence Deletion ; Transforming Growth Factor beta1/chemistry/genetics/*metabolism ; }, abstract = {The role of the hybrid domain in integrin affinity regulation is unknown, as is whether the kinetics of ligand binding is modulated by integrin affinity state. Here, we compare cell surface and soluble integrin αVβ6 truncation mutants for ligand-binding affinity, kinetics, and thermodynamics. Removal of the integrin transmembrane/cytoplasmic domains or lower legs has little effect on αVβ6 affinity, in contrast to β1 integrins. In integrin opening, rearrangement at the interface between the βI and hybrid domains is linked to remodeling at the ligand-binding site at the opposite end of the βI domain, which greatly increases in affinity in the open conformation. The larger size of the βI-hybrid interface in the closed state suggests that the hybrid domain stabilizes closing. In agreement, deletion of the hybrid domain raised affinity by 50-fold. Surface plasmon resonance and isothermal titration calorimetry gave similar results and the latter revealed tradeoffs between enthalpy and entropy not apparent from affinity. At extremely high affinity reached in Mn2+ with hybrid domain truncation, αVβ6 on-rate for both pro-TGF-β1 and fibronectin declined. The results suggest that the open conformation of αVβ6 has lower on-rate than the closed conformation, correlate with constriction of the ligand-binding pocket in open αVβ6 structures, and suggest that the extended-closed conformation is kinetically selected for ligand binding. Subsequent transition to the extended-open conformation is stabilized by its much higher affinity for ligand and would also be stabilized by force exerted across ligand-bound integrins by the actin cytoskeleton.}, } @article {pmid29378936, year = {2018}, author = {Hamrick, P and Lum, JAG and Ullman, MT}, title = {Child first language and adult second language are both tied to general-purpose learning systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1487-1492}, pmid = {29378936}, issn = {1091-6490}, mesh = {Adult ; Child ; Child, Preschool ; Humans ; *Language ; *Learning ; Memory ; Vocabulary ; }, abstract = {Do the mechanisms underlying language in fact serve general-purpose functions that preexist this uniquely human capacity? To address this contentious and empirically challenging issue, we systematically tested the predictions of a well-studied neurocognitive theory of language motivated by evolutionary principles. Multiple metaanalyses were performed to examine predicted links between language and two general-purpose learning systems, declarative and procedural memory. The results tied lexical abilities to learning only in declarative memory, while grammar was linked to learning in both systems in both child first language and adult second language, in specific ways. In second language learners, grammar was associated with only declarative memory at lower language experience, but with only procedural memory at higher experience. The findings yielded large effect sizes and held consistently across languages, language families, linguistic structures, and tasks, underscoring their reliability and validity. The results, which met the predicted pattern, provide comprehensive evidence that language is tied to general-purpose systems both in children acquiring their native language and adults learning an additional language. Crucially, if language learning relies on these systems, then our extensive knowledge of the systems from animal and human studies may also apply to this domain, leading to predictions that might be unwarranted in the more circumscribed study of language. Thus, by demonstrating a role for these systems in language, the findings simultaneously lay a foundation for potentially important advances in the study of this critical domain.}, } @article {pmid29378935, year = {2018}, author = {Tan, D and Piana, S and Dirks, RM and Shaw, DE}, title = {RNA force field with accuracy comparable to state-of-the-art protein force fields.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1346-E1355}, pmid = {29378935}, issn = {1091-6490}, mesh = {*Computational Biology ; Humans ; Models, Molecular ; *Molecular Dynamics Simulation ; *Nucleic Acid Conformation ; Proteins ; RNA/*chemistry ; Thermodynamics ; }, abstract = {Molecular dynamics (MD) simulation has become a powerful tool for characterizing at an atomic level of detail the conformational changes undergone by proteins. The application of such simulations to RNA structures, however, has proven more challenging, due in large part to the fact that the physical models ("force fields") available for MD simulations of RNA molecules are substantially less accurate in many respects than those currently available for proteins. Here, we introduce an extensive revision of a widely used RNA force field in which the parameters have been modified, based on quantum mechanical calculations and existing experimental information, to more accurately reflect the fundamental forces that stabilize RNA structures. We evaluate these revised parameters through long-timescale MD simulations of a set of RNA molecules that covers a wide range of structural complexity, including single-stranded RNAs, RNA duplexes, RNA hairpins, and riboswitches. The structural and thermodynamic properties measured in these simulations exhibited dramatically improved agreement with experimentally determined values. Based on the comparisons we performed, this RNA force field appears to achieve a level of accuracy comparable to that of state-of-the-art protein force fields, thus significantly advancing the utility of MD simulation as a tool for elucidating the structural dynamics and function of RNA molecules and RNA-containing biological assemblies.}, } @article {pmid29378934, year = {2018}, author = {Lu, L and Gutruf, P and Xia, L and Bhatti, DL and Wang, X and Vazquez-Guardado, A and Ning, X and Shen, X and Sang, T and Ma, R and Pakeltis, G and Sobczak, G and Zhang, H and Seo, DO and Xue, M and Yin, L and Chanda, D and Sheng, X and Bruchas, MR and Rogers, JA}, title = {Wireless optoelectronic photometers for monitoring neuronal dynamics in the deep brain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1374-E1383}, pmid = {29378934}, issn = {1091-6490}, support = {R01 MH112355/MH/NIMH NIH HHS/United States ; R21 EY027612/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Brain/*physiology ; Deep Brain Stimulation/*methods ; Male ; Mice ; Mice, Inbred C57BL ; Neurons/*physiology ; Optical Fibers ; Optogenetics/*instrumentation ; Photic Stimulation/*instrumentation ; *Wireless Technology ; }, abstract = {Capabilities for recording neural activity in behaving mammals have greatly expanded our understanding of brain function. Some of the most sophisticated approaches use light delivered by an implanted fiber-optic cable to optically excite genetically encoded calcium indicators and to record the resulting changes in fluorescence. Physical constraints induced by the cables and the bulk, size, and weight of the associated fixtures complicate studies on natural behaviors, including social interactions and movements in environments that include obstacles, housings, and other complex features. Here, we introduce a wireless, injectable fluorescence photometer that integrates a miniaturized light source and a photodetector on a flexible, needle-shaped polymer support, suitable for injection into the deep brain at sites of interest. The ultrathin geometry and compliant mechanics of these probes allow minimally invasive implantation and stable chronic operation. In vivo studies in freely moving animals demonstrate that this technology allows high-fidelity recording of calcium fluorescence in the deep brain, with measurement characteristics that match or exceed those associated with fiber photometry systems. The resulting capabilities in optical recordings of neuronal dynamics in untethered, freely moving animals have potential for widespread applications in neuroscience research.}, } @article {pmid29378933, year = {2018}, author = {Touboul, JD and Staver, AC and Levin, SA}, title = {On the complex dynamics of savanna landscapes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1336-E1345}, pmid = {29378933}, issn = {1091-6490}, mesh = {Climate ; Computer Simulation ; *Ecosystem ; *Forests ; *Grassland ; *Models, Biological ; Models, Theoretical ; *Trees ; }, abstract = {Simple mathematical models can exhibit rich and complex behaviors. Prototypical examples of these drawn from biology and other disciplines have provided insights that extend well beyond the situations that inspired them. Here, we explore a set of simple, yet realistic, models for savanna-forest vegetation dynamics based on minimal ecological assumptions. These models are aimed at understanding how vegetation interacts with both climate (a primary global determinant of vegetation structure) and feedbacks with chronic disturbances from fire. The model includes three plant functional types-grasses, savanna trees, and forest trees. Grass and (when they allow grass to persist in their subcanopy) savanna trees promote the spread of fires, which in turn, demographically limit trees. The model exhibits a spectacular range of behaviors. In addition to bistability, analysis reveals (i) that diverse cyclic behaviors (including limit and homo- and heteroclinic cycles) occur for broad ranges of parameter space, (ii) that large shifts in landscape structure can result from endogenous dynamics and not just from external drivers or from noise, and (iii) that introducing noise into this system induces resonant and inverse resonant phenomena, some of which have never been previously observed in ecological models. Ecologically, these results raise questions about how to evaluate complicated dynamics with data. Mathematically, they lead to classes of behaviors that are likely to occur in other models with similar structure.}, } @article {pmid29378648, year = {2018}, author = {Richardson, A and Muir, L and Mousdell, S and Sexton, D and Jones, S and Howl, J and Ross, K}, title = {Modulation of mitochondrial activity in HaCaT keratinocytes by the cell penetrating peptide Z-Gly-RGD(DPhe)-mitoparan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {82}, pmid = {29378648}, issn = {1756-0500}, mesh = {Animals ; Cell Line ; Cell Survival/drug effects ; Cell-Penetrating Peptides/*pharmacology ; Dose-Response Relationship, Drug ; Humans ; Keratinocytes/cytology/*drug effects/metabolism ; Membrane Potential, Mitochondrial/drug effects ; Mitochondria/*drug effects/metabolism ; Peptides/*pharmacology ; Wasp Venoms/*pharmacology ; }, abstract = {OBJECTIVE: Biologically active cell penetrating peptides (CPPs) are an emerging class of therapeutic agent. The wasp venom peptide mastoparan is an established CPP that modulates mitochondrial activity and triggers caspase-dependent apoptosis in cancer cells, as does the mastoparan analogue mitoparan (mitP). Mitochondrial depolarisation and activation of the caspase cascade also underpins the action of dithranol, a topical agent for treatment of psoriasis. The effects of a potent mitP analogue on mitochondrial activity were therefore examined to assess its potential as a novel approach for targeting mitochondria for the treatment of psoriasis.

RESULTS: In HaCaT keratinocytes treated with the mitP analogue Z-Gly-RGD(DPhe)-mitP for 24 h, a dose-dependent loss of mitochondrial activity was observed using the methyl-thiazolyl-tetrazolium (MTT) assay. At 10 μmol L-1, MTT activity was less than 30% that observed in untreated cells. Staining with the cationic dye JC-1 suggested that Z-Gly-RGD(DPhe)-mitP also dissipated the mitochondrial membrane potential, with a threefold increase in mitochondrial depolarisation levels. However, caspase activity appeared to be reduced by 24 h exposure to Z-Gly-RGD(DPhe)-mitP treatment. Furthermore, Z-Gly-RGD(DPhe)-mitP treatment had little effect on overall cell viability. Our findings suggest Z-Gly-RGD(DPhe)-mitP promotes the loss of mitochondrial activity but does not appear to evoke apoptosis in HaCaT keratinocytes.}, } @article {pmid29378638, year = {2018}, author = {Sains, P and Chana, KS and Sridhar, V and Sajid, MS}, title = {Pilot study on an innovative biosensor with a range of medical and surgical applications.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {81}, pmid = {29378638}, issn = {1756-0500}, mesh = {*Algorithms ; Animals ; Biosensing Techniques/*instrumentation/*methods ; Body Temperature/physiology ; Diagnostic Techniques and Procedures ; *Equipment Design ; Humans ; Organ Specificity ; Pilot Projects ; Reproducibility of Results ; Surgical Procedures, Operative ; Swine ; Temperature ; Water/chemistry ; }, abstract = {OBJECTIVES: The objective of this article is to briefly outline the utilization of biosensors in medicine and surgery and present diagnostic efficacy of thermal product (TP) based biosensor.

RESULTS: The working principle of biosensor is based on measuring TP of a material in contact with the sensor. When an electrical square wave pulse of certain amplitude and duration is passed through TP based biosensor, the generated heat from its higher resistance will be dissipated and recorded by the sensor. As the surrounding material composition changes, the dissipated heat split between the sensor substrate and surrounding material changes which can be correlated to the change in TP of the material. For biological tissues, it is known that the thermal properties of tissues are quite different for different layers in the body and hence the heat absorbed will be different. The experiments were conducted on biological and non-biological tissues. For data acquisition software LabView 2014 (64-bit) was used and software used for post-processing was MATLAB R2015a (64-bit). The resulting graphs of TP from various materials (oil, water, saline, acetone) and biological tissue (porcine belly, porcine thigh layers and porcine abdominal viscera) expressed prominent deflections indicating diagnostic efficacy of TP based biosensor.}, } @article {pmid29378633, year = {2018}, author = {Meisel, JS and Sfyroera, G and Bartow-McKenney, C and Gimblet, C and Bugayev, J and Horwinski, J and Kim, B and Brestoff, JR and Tyldsley, AS and Zheng, Q and Hodkinson, BP and Artis, D and Grice, EA}, title = {Commensal microbiota modulate gene expression in the skin.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {20}, pmid = {29378633}, issn = {2049-2618}, support = {R01 AI074878/AI/NIAID NIH HHS/United States ; K08 AR065577/AR/NIAMS NIH HHS/United States ; R01 AR066663/AR/NIAMS NIH HHS/United States ; R01-AR066663/AR/NIAMS NIH HHS/United States ; AI095608/NH/NIH HHS/United States ; R01 AI095466/AI/NIAID NIH HHS/United States ; AI087990/NH/NIH HHS/United States ; P30 AR069589/AR/NIAMS NIH HHS/United States ; AI095466/NH/NIH HHS/United States ; T32 HG000046/HG/NHGRI NIH HHS/United States ; AI083480/NH/NIH HHS/United States ; AI074878/NH/NIH HHS/United States ; R01 AI102942/AI/NIAID NIH HHS/United States ; R00-AR060873/AR/NIAMS NIH HHS/United States ; R21 AI087990/AI/NIAID NIH HHS/United States ; R01 NR015639/NR/NINR NIH HHS/United States ; AI061570/NH/NIH HHS/United States ; T32 AR007465/AR/NIAMS NIH HHS/United States ; R01-NR015639/NR/NINR NIH HHS/United States ; AI102942/NH/NIH HHS/United States ; P30-AR057217/AR/NIAMS NIH HHS/United States ; R21 AI083480/AI/NIAID NIH HHS/United States ; U01 AI095608/AI/NIAID NIH HHS/United States ; T32 HG000046/HG/NHGRI NIH HHS/United States ; R01 AI061570/AI/NIAID NIH HHS/United States ; P30 AR057217/AR/NIAMS NIH HHS/United States ; R01 AI097333/AI/NIAID NIH HHS/United States ; R00 AR060873/AR/NIAMS NIH HHS/United States ; AI097333/NH/NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Gastrointestinal Tract/immunology/*microbiology ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; *Gene Regulatory Networks ; Host-Pathogen Interactions ; Immunity, Innate ; Mice ; Microbiota ; Organ Specificity ; Sequence Analysis, RNA/methods ; Skin/immunology/*microbiology ; }, abstract = {BACKGROUND: The skin harbors complex communities of resident microorganisms, yet little is known of their physiological roles and the molecular mechanisms that mediate cutaneous host-microbe interactions. Here, we profiled skin transcriptomes of mice reared in the presence and absence of microbiota to elucidate the range of pathways and functions modulated in the skin by the microbiota.

RESULTS: A total of 2820 genes were differentially regulated in response to microbial colonization and were enriched in gene ontology (GO) terms related to the host-immune response and epidermal differentiation. Innate immune response genes and genes involved in cytokine activity were generally upregulated in response to microbiota and included genes encoding toll-like receptors, antimicrobial peptides, the complement cascade, and genes involved in IL-1 family cytokine signaling and homing of T cells. Our results also reveal a role for the microbiota in modulating epidermal differentiation and development, with differential expression of genes in the epidermal differentiation complex (EDC). Genes with correlated co-expression patterns were enriched in binding sites for the transcription factors Klf4, AP-1, and SP-1, all implicated as regulators of epidermal differentiation. Finally, we identified transcriptional signatures of microbial regulation common to both the skin and the gastrointestinal tract.

CONCLUSIONS: With this foundational approach, we establish a critical resource for understanding the genome-wide implications of microbially mediated gene expression in the skin and emphasize prospective ways in which the microbiome contributes to skin health and disease.}, } @article {pmid29378632, year = {2018}, author = {Corbett, DB and Fennell, C and Peroutky, K and Kingsley, JD and Glickman, EL}, title = {The effects of a 12-week worksite physical activity intervention on anthropometric indices, blood pressure indices, and plasma biomarkers of cardiovascular disease risk among university employees.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {80}, pmid = {29378632}, issn = {1756-0500}, mesh = {Adult ; Biomarkers/*blood ; Blood Pressure/*physiology ; Body Mass Index ; Body Weight/*physiology ; Cardiovascular Diseases/blood/*physiopathology/prevention & control ; Exercise/*physiology ; Female ; Humans ; Lipids/blood ; Male ; Middle Aged ; Obesity/blood/physiopathology ; Occupational Health/statistics & numerical data ; Risk Factors ; Universities ; *Workplace ; }, abstract = {BACKGROUND: To determine the effectiveness of a low-cost 12-week worksite physical activity intervention targeting a goal of 10,000 steps per day on reducing anthropometric indices, blood pressure indices, and plasma biomarkers of cardiovascular disease (CVD) risk among the employees of a major university.

METHODS: Fifty university employees (n = 43 female, n = 7 male; mean age = 48 ± 10 years) participated in the 12-week physical activity intervention (60 min, 3 day/week). Each session included both aerobic (cardiorespiratory endurance) and muscle-strengthening (resistance) physical activity using existing university facilities and equipment. Anthropometric indices, blood pressure indices, and plasma biomarkers of CVD risk assessed included those for obesity (body mass index), hypertension (systolic blood pressure, SBP; diastolic blood pressure, DBP), dyslipidemia (high-density lipoprotein, HDL; low-density lipoprotein, LDL; total serum cholesterol), and prediabetes (impaired fasting glucose, IFG). Steps per day were assessed using a wrist-worn activity monitor. Participants were given the goal of 10,000 steps per day and categorized as either compliers (≥ 10,000 steps per day on average) or non-compliers (< 10,000 steps per day on average) based on their ability to achieve this goal.

RESULTS: Overall, 34% of participants at baseline were already at an elevated risk of CVD due to age. On average, 28% of participants adhered to the goal of 10,000 steps per day. After 12-weeks, participants in both groups (compliers and non-compliers) had lower BMI scores (p < 0.001), lower HDL scores (p < 0.034), and higher IFG scores (p < 0.001). The non-compliers had a greater reduction of BMI scores than the compliers (p = 0.003). Participants at risk for CVD had greater reductions than those not at risk for several risk factors, including SBP (p = 0.020), DBP (p = 0.028), IFG (p = 0.002), LDL (p = 0.006), and total serum cholesterol (p = 0.009).

CONCLUSION: While the physical activity intervention showed mixed results overall with both favorable changes in anthropometric indices yet unfavorable changes in plasma biomarkers, it was particularly beneficial in regards to both blood pressure indices and plasma biomarkers among those already at risk of CVD. Trial registration ClinicalTrials.gov NCT03385447; retrospectively registered.}, } @article {pmid29378628, year = {2018}, author = {Dombrowski, JE and Martin, RC}, title = {Activation of MAP kinases by green leaf volatiles in grasses.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {79}, pmid = {29378628}, issn = {1756-0500}, mesh = {Electrophoresis, Polyacrylamide Gel ; Enzyme Activation ; Lolium/enzymology ; Lycopersicon esculentum/enzymology ; Mitogen-Activated Protein Kinases/chemistry/*metabolism ; Molecular Weight ; Plant Leaves/*metabolism ; Poaceae/classification/*metabolism ; Species Specificity ; Stress, Mechanical ; Time Factors ; Volatile Organic Compounds/*metabolism ; }, abstract = {OBJECTIVE: Previously we have shown that mechanical wounding and volatiles released from cut grass, activated a 46 and 44 kDa mitogen-activated protein kinase (MAPK) in the model grass species Lolium temulentum (Lt). MAPKs play an important role as signal relays that connect incoming stress signals and stress responses. Since green leaf volatiles (GLV) are released during wounding, we wanted determine if specific compounds contained in the GLV mixture or if GLV generated from other plant species could activate these Lt MAPKs.

RESULTS: Our analysis found that just a 1-min exposure to GLV was enough to activate the Lt 46 kDa MAPK within 3 min and the 44 kDa MAPK within 15 min. This activation pattern showed similar kinetics to those observed after wounding, and the GLV and wound activated bands associated with these MAPKs displayed identical migration on sodium dodecyl sulfate polyacrylamide gels. Thirteen different commercially available plant volatiles (alcohols, aldehydes and ketones) were tested and all thirteen volatile compounds were able to activate these same Lt MAPKs. Furthermore, GLV derived from three other grass species as well as tomato, a dicot, were also shown to activate these MAPKs in Lt.}, } @article {pmid29378627, year = {2018}, author = {Broberg, M and Doonan, J and Mundt, F and Denman, S and McDonald, JE}, title = {Integrated multi-omic analysis of host-microbiota interactions in acute oak decline.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {21}, pmid = {29378627}, issn = {2049-2618}, support = {TH0108//Department for Environment, Food and Rural Affairs/International ; }, mesh = {Bacterial Proteins/genetics/metabolism ; Enterobacteriaceae/genetics/metabolism/*pathogenicity ; Gene Expression Profiling ; Genomics/*methods ; Host-Pathogen Interactions ; Microbiota ; Plant Diseases/*microbiology ; Proteomics ; Quercus/*microbiology ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Virulence Factors/*genetics/*metabolism ; }, abstract = {BACKGROUND: Britain's native oak species are currently under threat from acute oak decline (AOD), a decline-disease where stem bleeds overlying necrotic lesions in the inner bark and larval galleries of the bark-boring beetle, Agrilus biguttatus, represent the primary symptoms. It is known that complex interactions between the plant host and its microbiome, i.e. the holobiont, significantly influence the health status of the plant. In AOD, necrotic lesions are caused by a microbiome shift to a pathobiome consisting predominantly of Brenneria goodwinii, Gibbsiella quercinecans, Rahnella victoriana and potentially other bacteria. However, the specific mechanistic processes of the microbiota causing tissue necrosis, and the host response, have not been established and represent a barrier to understanding and managing this decline.

RESULTS: We profiled the metagenome, metatranscriptome and metaproteome of inner bark tissue from AOD symptomatic and non-symptomatic trees to characterise microbiota-host interactions. Active bacterial virulence factors such as plant cell wall-degrading enzymes, reactive oxygen species defence and flagella in AOD lesions, along with host defence responses including reactive oxygen species, cell wall modification and defence regulators were identified. B. goodwinii dominated the lesion microbiome, with significant expression of virulence factors such as the phytopathogen effector avrE. A smaller proportion of microbiome activity was attributed to G. quercinecans and R. victoriana. In addition, we describe for the first time the potential role of two previously uncharacterised Gram-positive bacteria predicted from metagenomic binning and identified as active in the AOD lesion metatranscriptome and metaproteome, implicating them in lesion formation.

CONCLUSIONS: This multi-omic study provides novel functional insights into microbiota-host interactions in AOD, a complex arboreal decline disease where polymicrobial-host interactions result in lesion formation on tree stems. We present the first descriptions of holobiont function in oak health and disease, specifically, the relative lesion activity of B. goodwinii, G. quercinecans, Rahnella victoriana and other bacteria. Thus, the research presented here provides evidence of some of the mechanisms used by members of the lesion microbiome and a template for future multi-omic research into holobiont characterisation, plant polymicrobial diseases and pathogen defence in trees.}, } @article {pmid29378592, year = {2018}, author = {Schartl, M and Schories, S and Wakamatsu, Y and Nagao, Y and Hashimoto, H and Bertin, C and Mourot, B and Schmidt, C and Wilhelm, D and Centanin, L and Guiguen, Y and Herpin, A}, title = {Sox5 is involved in germ-cell regulation and sex determination in medaka following co-option of nested transposable elements.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {16}, pmid = {29378592}, issn = {1741-7007}, abstract = {BACKGROUND: Sex determination relies on a hierarchically structured network of genes, and is one of the most plastic processes in evolution. The evolution of sex-determining genes within a network, by neo- or sub-functionalization, also requires the regulatory landscape to be rewired to accommodate these novel gene functions. We previously showed that in medaka fish, the regulatory landscape of the master male-determining gene dmrt1bY underwent a profound rearrangement, concomitantly with acquiring a dominant position within the sex-determining network. This rewiring was brought about by the exaptation of a transposable element (TE) called Izanagi, which is co-opted to act as a silencer to turn off the dmrt1bY gene after it performed its function in sex determination.

RESULTS: We now show that a second TE, Rex1, has been incorporated into Izanagi. The insertion of Rex1 brought in a preformed regulatory element for the transcription factor Sox5, which here functions in establishing the temporal and cell-type-specific expression pattern of dmrt1bY. Mutant analysis demonstrates the importance of Sox5 in the gonadal development of medaka, and possibly in mice, in a dmrt1bY-independent manner. Moreover, Sox5 medaka mutants have complete female-to-male sex reversal.

CONCLUSIONS: Our work reveals an unexpected complexity in TE-mediated transcriptional rewiring, with the exaptation of a second TE into a network already rewired by a TE. We also show a dual role for Sox5 during sex determination: first, as an evolutionarily conserved regulator of germ-cell number in medaka, and second, by de novo regulation of dmrt1 transcriptional activity during primary sex determination due to exaptation of the Rex1 transposable element.}, } @article {pmid29378521, year = {2018}, author = {Wongphutorn, P and Chomvarin, C and Sripa, B and Namwat, W and Faksri, K}, title = {Detection and genotyping of Helicobacter pylori in saliva versus stool samples from asymptomatic individuals in Northeastern Thailand reveals intra-host tissue-specific H. pylori subtypes.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {10}, pmid = {29378521}, issn = {1471-2180}, support = {NA//Khon Kaen University/International ; MRG 5980002//Thailand Research Fund/International ; RTA 5680006//Thailand Research Fund/International ; }, mesh = {Adolescent ; Adult ; Bacterial Proteins/genetics ; DNA, Bacterial ; Feces/*microbiology ; Female ; Genetic Variation ; *Genotype ; Helicobacter Infections/*epidemiology/*microbiology ; Helicobacter pylori/classification/*genetics/*isolation & purification/pathogenicity ; Humans ; Intestines/microbiology ; Male ; Middle Aged ; Mouth/microbiology ; Phylogeny ; Polymerase Chain Reaction ; Prevalence ; RNA, Ribosomal, 16S/genetics ; Risk Factors ; Saliva/*microbiology ; Thailand/epidemiology ; Young Adult ; }, abstract = {BACKGROUND: Two-thirds of the world's population is thought to be infected by Helicobacter pylori. Although most people infected with H. pylori are asymptomatic, this pathogen is associated with several gastric pathologies including cancer. The risk factors for colonization are still unclear and the genetic diversity within individual hosts has never been clearly investigated.

RESULT: This study determined the prevalence of, and explored risk factors for, H. pylori infection directly from paired saliva (n = 110) and stool (n = 110) samples from asymptomatic persons in Northeast Thailand. Samples were subjected to indirect immunofluorescence assay (IFA), 16S rRNA-based real-time PCR and vacA-based semi-nested PCR. Partial vacA gene sequences of H. pylori were compared between saliva and stool samples. The overall prevalence of H. pylori infection in our asymptomatic study population was 64%. Age, gender, occupation and frequency of brushing teeth were not found to be associated with H. pylori colonization. The vacA gene was successfully sequenced from both saliva and stool samples of 12 individuals. For seven of these individuals, saliva and stool sequences fell into different clusters on a phylogenetic tree, indicating intra-host genetic variation of H. pylori.

CONCLUSION: This study reports a high prevalence of H. pylori infection in asymptomatic persons in this region of Thailand and demonstrates that genotypes (vacA gene sequences) of H. pylori may differ between the oral cavity and intestinal tract.}, } @article {pmid29378520, year = {2018}, author = {Ceballos, FC and Hazelhurst, S and Ramsay, M}, title = {Assessing runs of Homozygosity: a comparison of SNP Array and whole genome sequence low coverage data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {106}, pmid = {29378520}, issn = {1471-2164}, mesh = {*Genomics ; Heterozygote ; *Homozygote ; Humans ; *Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide ; Software ; }, abstract = {BACKGROUND: Runs of Homozygosity (ROH) are genomic regions where identical haplotypes are inherited from each parent. Since their first detection due to technological advances in the late 1990s, ROHs have been shedding light on human population history and deciphering the genetic basis of monogenic and complex traits and diseases. ROH studies have predominantly exploited SNP array data, but are gradually moving to whole genome sequence (WGS) data as it becomes available. WGS data, covering more genetic variability, can add value to ROH studies, but require additional considerations during analysis.

RESULTS: Using SNP array and low coverage WGS data from 1885 individuals from 20 world populations, our aims were to compare ROH from the two datasets and to establish software conditions to get comparable results, thus providing guidelines for combining disparate datasets in joint ROH analyses. By allowing heterozygous SNPs per window, using the PLINK homozygosity function and non-parametric analysis, we were able to obtain non-significant differences in number ROH, mean ROH size and total sum of ROH between data sets using the different technologies for almost all populations.

CONCLUSIONS: By allowing 3 heterozygous SNPs per ROH when dealing with WGS low coverage data, it is possible to establish meaningful comparisons between data using SNP array and WGS low coverage technologies.}, } @article {pmid29378514, year = {2018}, author = {Pokharel, K and Peippo, J and Honkatukia, M and Seppälä, A and Rautiainen, J and Ghanem, N and Hamama, TM and Crowe, MA and Andersson, M and Li, MH and Kantanen, J}, title = {Integrated ovarian mRNA and miRNA transcriptome profiling characterizes the genetic basis of prolificacy traits in sheep (Ovis aries).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {104}, pmid = {29378514}, issn = {1471-2164}, support = {250633//Suomen Akatemia/International ; 250677//Suomen Akatemia/International ; 31272413//National Natural Science Foundation of China/International ; }, mesh = {Animals ; Breeding ; Female ; Gene Expression Profiling/*methods ; MicroRNAs/*genetics ; Ovary/cytology/*metabolism ; Phenotype ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; RNA, Messenger/*genetics ; Reproduction ; Sheep/*genetics/*growth & development ; }, abstract = {BACKGROUND: The highly prolific breeds of domestic sheep (Ovis aries) are globally valuable genetic resources for sheep industry. Genetic, nutritional and other environmental factors affect prolificacy traits in sheep. To improve our knowledge of the sheep prolificacy traits, we conducted mRNA-miRNA integrated profiling of ovarian tissues from two pure breeds with large (Finnsheep) vs. small (Texel) litter sizes and their F1 crosses, half of which were fed a flushing diet.

RESULTS: Among the samples, 16,402 genes (60.6% known ovine genes) were expressed, 79 novel miRNAs were found, and a cluster of miRNAs on chromosome 18 was detected. The majority of the differentially expressed genes between breeds were upregulated in the Texel with low prolificacy, owing to the flushing diet effect, whereas a similar pattern was not detected in the Finnsheep. F1 ewes responded similarly to Finnsheep rather than displaying a performance intermediate between the two pure breeds.

CONCLUSIONS: The identification and characterization of differentially expressed genes and miRNAs in the ovaries of sheep provided insights into genetic and environmental factors affecting prolificacy traits. The three genes (CST6, MEPE and HBB) that were differentially expressed between the group of Finnsheep and Texel ewes kept in normal diet appeared to be candidate genes of prolificacy traits and will require further validation.}, } @article {pmid29378511, year = {2018}, author = {Pan, L and Meng, C and Wang, J and Ma, X and Fan, X and Yang, Z and Zhou, M and Zhang, X}, title = {Integrated omics data of two annual ryegrass (Lolium multiflorum L.) genotypes reveals core metabolic processes under drought stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {26}, pmid = {29378511}, issn = {1471-2229}, support = {CARS-35-05//The earmarked fund for Modern Agro-industry Technology Research System/International ; 2014CB138705//The National Basic Research Program (973 program) in China/International ; NSFC 31372363//The National Natural Science Foundation of China/International ; }, mesh = {*Droughts ; Gene Regulatory Networks ; *Genotype ; Lolium/*physiology ; Plant Proteins/*genetics/metabolism ; Stress, Physiological ; }, abstract = {BACKGROUND: Annual ryegrass (Lolium multiflorum L.) is a commercially important, widely distributed forage crop that is used in the production of hay and silage worldwide. Drought has been a severe environmental constraint in its production. Nevertheless, only a handful of studies have examined the impact of short-term drought stress on annual ryegrass. The aim of this study was to explore how stress-induced core metabolic processes enhance drought tolerance, or adaptation to drought, in annual ryegrass.

RESULTS: We profiled the transcriptomes, proteomes, and metabolomes of two annual ryegrass genotypes: the drought-resistant genotype "Abundant 10" and drought-susceptible genotype "Adrenalin 11." We identified differentially expressed metabolites and their corresponding proteins and transcripts that are involved in 23 core metabolic processes, in response to short-term drought stress. Protein-gene-metabolite correlation networks were built to reveal the relationships between the expression of transcripts, proteins, and metabolites in drought-resistant annual ryegrass. Furthermore, integrated metabolic pathways were used to observe changes in enzymes corresponding with levels of amino acids, lipids, carbohydrate conjugates, nucleosides, alkaloids and their derivatives, and pyridines and their derivatives. The resulting omics data underscored the significance of 23 core metabolic processes on the enhancement of drought tolerance or adaptation to drought in annual ryegrass.

CONCLUSIONS: The regulatory networks were inferred using MCoA and correlation analysis to reveal the relationships among the expression of transcripts, proteins, and metabolites that highlight the corresponding elements of these core metabolic pathways. Our results provide valuable insight into the molecular mechanisms of drought resistance, and represent a promising strategy toward the improvement of drought tolerance in annual ryegrass.}, } @article {pmid29378510, year = {2018}, author = {Klonowska, A and Melkonian, R and Miché, L and Tisseyre, P and Moulin, L}, title = {Transcriptomic profiling of Burkholderia phymatum STM815, Cupriavidus taiwanensis LMG19424 and Rhizobium mesoamericanum STM3625 in response to Mimosa pudica root exudates illuminates the molecular basis of their nodulation competitiveness and symbiotic evolutionary history.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {105}, pmid = {29378510}, issn = {1471-2164}, support = {ANR-09-JCJC-0046//Agence Nationale de la Recherche/International ; }, mesh = {Burkholderia/*genetics/metabolism ; Cupriavidus/*genetics/metabolism ; Gene Expression Profiling ; Genome, Bacterial ; Microbial Interactions ; Mimosa/*microbiology ; Plant Root Nodulation/*genetics ; Plant Roots/physiology ; Rhizobium/*genetics/metabolism ; Symbiosis/genetics ; }, abstract = {BACKGROUND: Rhizobial symbionts belong to the classes Alphaproteobacteria and Betaproteobacteria (called "alpha" and "beta"-rhizobia). Most knowledge on the genetic basis of symbiosis is based on model strains belonging to alpha-rhizobia. Mimosa pudica is a legume that offers an excellent opportunity to study the adaptation toward symbiotic nitrogen fixation in beta-rhizobia compared to alpha-rhizobia. In a previous study (Melkonian et al., Environ Microbiol 16:2099-111, 2014) we described the symbiotic competitiveness of M. pudica symbionts belonging to Burkholderia, Cupriavidus and Rhizobium species.

RESULTS: In this article we present a comparative analysis of the transcriptomes (by RNAseq) of B. phymatum STM815 (BP), C. taiwanensis LMG19424 (CT) and R. mesoamericanum STM3625 (RM) in conditions mimicking the early steps of symbiosis (i.e. perception of root exudates). BP exhibited the strongest transcriptome shift both quantitatively and qualitatively, which mirrors its high competitiveness in the early steps of symbiosis and its ancient evolutionary history as a symbiont, while CT had a minimal response which correlates with its status as a younger symbiont (probably via acquisition of symbiotic genes from a Burkholderia ancestor) and RM had a typical response of Alphaproteobacterial rhizospheric bacteria. Interestingly, the upregulation of nodulation genes was the only common response among the three strains; the exception was an up-regulated gene encoding a putative fatty acid hydroxylase, which appears to be a novel symbiotic gene specific to Mimosa symbionts.

CONCLUSION: The transcriptional response to root exudates was correlated to each strain nodulation competitiveness, with Burkholderia phymatum appearing as the best specialised symbiont of Mimosa pudica.}, } @article {pmid29378509, year = {2018}, author = {Guan, Q and Yan, H and Chen, Y and Zheng, B and Cai, H and He, J and Song, K and Guo, Y and Ao, L and Liu, H and Zhao, W and Wang, X and Guo, Z}, title = {Quantitative or qualitative transcriptional diagnostic signatures? A case study for colorectal cancer.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {99}, pmid = {29378509}, issn = {1471-2164}, support = {81372213//National Natural Science Foundation of China/International ; 81572935//National Natural Science Foundation of China/International ; 21534008//National Natural Science Foundation of China/International ; 61601151//National Natural Science Foundation of China/International ; 81602738//National Natural Science Foundation of China (CN)/International ; 2016Y9044//Joint Scientific and Technology Innovation Fund of Fujian Province/International ; }, mesh = {Algorithms ; Bayes Theorem ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; Colorectal Neoplasms/*diagnosis/*genetics ; Gene Expression Profiling/*methods ; *Gene Expression Regulation, Neoplastic ; Humans ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Due to experimental batch effects, the application of a quantitative transcriptional signature for disease diagnoses commonly requires inter-sample data normalization, which would be hardly applicable under common clinical settings. Many cancers might have qualitative differences with the non-cancer states in the gene expression pattern. Therefore, it is reasonable to explore the power of qualitative diagnostic signatures which are robust against experimental batch effects and other random factors.

RESULTS: Firstly, using data of technical replicate samples from the MicroArray Quality Control (MAQC) project, we demonstrated that the low-throughput PCR-based technologies also exist large measurement variations for gene expression even when the samples were measured in the same test site. Then, we demonstrated the critical limitation of low stability for classifiers based on quantitative transcriptional signatures in applications to individual samples through a case study using a support vector machine and a naïve Bayesian classifier to discriminate colorectal cancer tissues from normal tissues. To address this problem, we identified a signature consisting of three gene pairs for discriminating colorectal cancer tissues from non-cancer (normal and inflammatory bowel disease) tissues based on within-sample relative expression orderings (REOs) of these gene pairs. The signature was well verified using 22 independent datasets measured by different microarray and RNA_seq platforms, obviating the need of inter-sample data normalization.

CONCLUSIONS: Subtle quantitative information of gene expression measurements tends to be unstable under current technical conditions, which will introduce uncertainty to clinical applications of the quantitative transcriptional diagnostic signatures. For diagnosis of disease states with qualitative transcriptional characteristics, the qualitative REO-based signatures could be robustly applied to individual samples measured by different platforms.}, } @article {pmid29378340, year = {2018}, author = {Hu, Y and Cai, Q and Tian, S and Ge, Y and Yuan, Z and Hu, X}, title = {Regulator DegU is required for multicellular behavior in Lysinibacillus sphaericus.}, journal = {Research in microbiology}, volume = {169}, number = {3}, pages = {177-187}, doi = {10.1016/j.resmic.2017.12.006}, pmid = {29378340}, issn = {1769-7123}, mesh = {Bacillus/*physiology ; Bacterial Proteins/*genetics/metabolism ; Bacterial Toxins/genetics/metabolism ; Biofilms/growth & development ; *Gene Expression Regulation, Bacterial ; Mutation ; *Phenotype ; Phosphorylation ; Sequence Deletion ; Signal Transduction ; Spores, Bacterial ; Virulence ; }, abstract = {DegS and DegU make up a two component system belonging to a class of signal transduction systems that play important roles in a broad range of bacterial responses to the environment. However, little study has been done to explore the physiological functions of DegS-DegU in mosquitocidal Lysinibacillus sphaericus. In this study, it was found that deletion of degU or degS-degU inhibited the swarming motility, biofilm formation, sporulation and binary toxin production through regulating the related genes, and phosphorylation was necessary for the functions of DegU. Based on the findings, a regulation network mediated by DegU was delineated. Both DegU-pi and Spo0A-pi positively regulates genes which are linked with the transition from stage Ⅱ to the end of the sporulation process and also influences the production of binary toxins via regulation on sigE. Both DegU-pi and Spo0A-pi negatively regulate abrB/sinR and influence the biofilm formation. DegU-pi can positively regulate the motility via the regulation on sigD. Whether the regulations are directly or indirectly need to be explored. Moreover, Spo0A-pi may indirectly regulate the swarming motility through negatively regulating DegU. It was concluded that DegU is a global transcriptional regulator on cell swarming motility, biofilm formation, sporulation and virulence in L. sphaericus.}, } @article {pmid29378339, year = {2018}, author = {Vester, B}, title = {The cfr and cfr-like multiple resistance genes.}, journal = {Research in microbiology}, volume = {169}, number = {2}, pages = {61-66}, doi = {10.1016/j.resmic.2017.12.003}, pmid = {29378339}, issn = {1769-7123}, mesh = {Animals ; Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/*enzymology/genetics/isolation & purification ; Bacterial Infections/microbiology ; Bacterial Proteins/genetics/*metabolism ; *Drug Resistance, Multiple, Bacterial ; Humans ; Methyltransferases/genetics/*metabolism ; }, abstract = {The Cfr methyl transferase causes an RNA methylation of the bacterial ribosomes impeding reduced or abolished binding of many antibiotics acting at the peptidyl transferase center. It provides multi-resistance to eight classes of antibiotics, most of which are in clinical and veterinary use. The cfr gene is found in various bacteria in many geographical locations and placed on plasmids or associated with transposons. Cfr-related genes providing similar resistance have been identified in Bacillales, and now also in the pathogens Clostridium difficile and Enterococcus faecium. In addition, the presence of the cfr gene has been detected in harbours and food markets.}, } @article {pmid29378338, year = {2018}, author = {Wang, X and Cao, X and Li, S and Ou, Q and Lin, D and Yao, Z and Chen, S and Wu, C and Wen, G and Ye, X}, title = {Phenotypic and molecular characterization of Streptococcus agalactiae colonized in Chinese pregnant women: predominance of ST19/III and ST17/III.}, journal = {Research in microbiology}, volume = {169}, number = {2}, pages = {101-107}, doi = {10.1016/j.resmic.2017.12.004}, pmid = {29378338}, issn = {1769-7123}, mesh = {Adult ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/genetics/metabolism ; Drug Resistance, Bacterial ; Erythromycin/pharmacology ; Female ; Genotype ; Humans ; Microbial Sensitivity Tests ; Phenotype ; Pregnancy ; Pregnancy Complications/*microbiology ; Pregnant Women ; Streptococcal Infections/*microbiology ; Streptococcus agalactiae/classification/drug effects/*genetics/*isolation & purification ; Virulence Factors/genetics/metabolism ; Young Adult ; }, abstract = {Streptococcus agalactiae (GBS) remains a major cause of invasive infections in neonates and pregnant women. Our aim was to evaluate the phenotypic and molecular characteristics of GBS isolates in order to reveal potential relationships among molecular characteristics and differences in genotype-phenotype characteristics between ST17 and ST19. A total of 104 GBS isolates were collected from pregnant women. All isolates were tested for antibiotic susceptibility by disk diffusion method and molecular characteristics, including antibiotic-resistant genes, virulence genes, serotypes and STs. The prevalence of GBS colonization in pregnant women was 4.9%. All isolates were susceptible to penicillin, but a high prevalence of resistance was observed for tetracycline (76.9%) and erythromycin (72.1%), with the predominant resistant genes being tet(M), tet(O), erm(B) and mef (A/E). The most frequent serotypes were III, Ia and V, and the predominant STs were ST19, ST17, ST12, ST10 and ST651. A potential correlation existed between STs, serotypes and alp genes, with ST19/III/rib and ST17/III/rib as the most prevalent clones. Notably, we observed significant differences in phenotypic and genotypic characteristics between ST17 [levofloxacin-susceptible and tet(O)-positive] and ST19 [levofloxacin-resistant and tet(O)-negative]. Our findings reveal a high prevalence of ST19/III and ST17/III and significant characteristic differences between them.}, } @article {pmid29378337, year = {2018}, author = {Lurthy, T and Alloisio, N and Fournier, P and Anchisi, S and Ponsero, A and Normand, P and Pujic, P and Boubakri, H}, title = {Molecular response to nitrogen starvation by Frankia alni ACN14a revealed by transcriptomics and functional analysis with a fosmid library in Escherichia coli.}, journal = {Research in microbiology}, volume = {169}, number = {2}, pages = {90-100}, doi = {10.1016/j.resmic.2017.12.002}, pmid = {29378337}, issn = {1769-7123}, mesh = {Alnus/microbiology ; Bacterial Proteins/genetics/metabolism ; Escherichia coli/*genetics/metabolism ; Frankia/*genetics/physiology ; Gene Expression Regulation, Bacterial ; Gene Library ; Nitrogen/*metabolism ; Symbiosis ; Transcriptome ; }, abstract = {The transcriptome of Frankia alni strain ACN14a was compared between in vitro ammonium-replete (N-replete) and ammonium-free dinitrogen-fixing (N-fixing) conditions using DNA arrays. A Welch-test (p < 0.05) revealed significant upregulation of 252 genes under N-fixing vs. N-replete (fold-change (FC) ≥ 2), as well as significant downregulation of 48 other genes (FC ≤ 0.5). Interestingly, there were 104 Frankia genes upregulated in vitro that were also significantly upregulated in symbiosis with Alnus glutinosa, while the other 148 genes were not, showing that the physiology of in vitro fixation is markedly different from that under symbiotic conditions. In particular,in vitro fixing cells were seen to upregulate genes identified as coding for a nitrite reductase, and amidases that were not upregulated in symbiosis. Confirmatory assays for nitrite reductase showed that Frankia indeed reduced nitrite and used it as a nitrogen source. An Escherichia coli fosmid clone carrying the nirB region was able to grow better in the presence of 5 mM nitrite than without it, confirming the function of the genome region. The physiological pattern that emerges shows that Frankia undergoes nitrogen starvation that induces a molecular response different from that seen in symbiosis.}, } @article {pmid29378247, year = {2018}, author = {Fagua, G and Condamine, FL and Brunet, BMT and Clamens, AL and Laroche, J and Levesque, RC and Cusson, M and Sperling, FAH}, title = {Convergent herbivory on conifers by Choristoneura moths after boreal forest formation.}, journal = {Molecular phylogenetics and evolution}, volume = {123}, number = {}, pages = {35-43}, doi = {10.1016/j.ympev.2018.01.013}, pmid = {29378247}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Calibration ; Coniferophyta/*parasitology ; DNA, Mitochondrial/genetics ; Genome, Mitochondrial ; Herbivory/*physiology ; Moths/genetics/*physiology ; Phylogeny ; *Taiga ; Time Factors ; }, abstract = {Mitogenomes are useful markers for phylogenetic studies across a range of taxonomic levels. Here, we focus on mitogenome variation across the tortricid moth genus Choristoneura and particularly the spruce budworm (Choristoneura fumiferana) species complex, a notorious pest group of North American conifer forests. Phylogenetic relationships of Tortricidae, representing two subfamilies, four tribes and nine genera, were analyzed using 21 mitogenomes. These included six newly-sequenced mitogenomes for species in the spruce budworm complex plus three additional Choristoneura species and 12 previously published mitogenomes from other tortricids and one from the Cossidae. We evaluated the phylogenetic informativeness of the mitogenomes and reconstructed a time-calibrated tree with fossil and secondary calibrations. We found that tortricid mitogenomes had conserved protein and ribosomal regions, and analysis of all protein-coding plus ribosomal genes together provided an efficient marker at any taxonomic rank. The time-calibrated phylogeny showed evolutionary convergence of conifer feeding within Choristoneura, with two independent lineages, the Nearctic spruce budworm complex and the Palearctic species Choristoneura murinana, both shifting onto conifers about 11 million years ago from angiosperms. These two host-plant shifts both occurred after the formation of boreal forest in the late Miocene. Haplotype diversification within the spruce budworm complex occurred in the last 4 million years, and is probably linked to the initial cooling cycles of the Northern Hemisphere in the Pliocene.}, } @article {pmid29378032, year = {2018}, author = {Liang, P and Saqib, HSA and Zhang, X and Zhang, L and Tang, H}, title = {Single-Base Resolution Map of Evolutionary Constraints and Annotation of Conserved Elements across Major Grass Genomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {473-488}, pmid = {29378032}, issn = {1759-6653}, mesh = {Base Sequence ; Conserved Sequence ; DNA, Plant/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Plant ; *Genome, Plant ; Genomics ; Magnoliopsida/genetics ; Phylogeny ; Poaceae/*genetics ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Untranslated Regions ; }, abstract = {Conserved noncoding sequences (CNSs) are evolutionarily conserved DNA sequences that do not encode proteins but may have potential regulatory roles in gene expression. CNS in crop genomes could be linked to many important agronomic traits and ecological adaptations. Compared with the relatively mature exon annotation protocols, efficient methods are lacking to predict the location of noncoding sequences in the plant genomes. We implemented a computational pipeline that is tailored to the comparisons of plant genomes, yielding a large number of conserved sequences using rice genome as the reference. In this study, we used 17 published grass genomes, along with five monocot genomes as well as the basal angiosperm genome of Amborella trichopoda. Genome alignments among these genomes suggest that at least 12.05% of the rice genome appears to be evolving under constraints in the Poaceae lineage, with close to half of the evolutionarily constrained sequences located outside protein-coding regions. We found evidence for purifying selection acting on the conserved sequences by analyzing segregating SNPs within the rice population. Furthermore, we found that known functional motifs were significantly enriched within CNS, with many motifs associated with the preferred binding of ubiquitous transcription factors. The conserved elements that we have curated are accessible through our public database and the JBrowse server. In-depth functional annotations and evolutionary dynamics of the identified conserved sequences provide a solid foundation for studying gene regulation, genome evolution, as well as to inform gene isolation for cereal biologists.}, } @article {pmid29378020, year = {2018}, author = {Hillmann, F and Forbes, G and Novohradská, S and Ferling, I and Riege, K and Groth, M and Westermann, M and Marz, M and Spaller, T and Winckler, T and Schaap, P and Glöckner, G}, title = {Multiple Roots of Fruiting Body Formation in Amoebozoa.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {591-606}, pmid = {29378020}, issn = {1759-6653}, mesh = {Amoebozoa/cytology/*genetics/*growth & development ; Cell Communication ; Dictyostelium/cytology/genetics/growth & development ; Evolution, Molecular ; *Gene Expression Regulation, Developmental ; Phylogeny ; Protozoan Proteins/genetics ; Transcriptome ; }, abstract = {Establishment of multicellularity represents a major transition in eukaryote evolution. A subgroup of Amoebozoa, the dictyosteliids, has evolved a relatively simple aggregative multicellular stage resulting in a fruiting body supported by a stalk. Protosteloid amoeba, which are scattered throughout the amoebozoan tree, differ by producing only one or few single stalked spores. Thus, one obvious difference in the developmental cycle of protosteliids and dictyosteliids seems to be the establishment of multicellularity. To separate spore development from multicellular interactions, we compared the genome and transcriptome of a Protostelium species (Protostelium aurantium var. fungivorum) with those of social and solitary members of the Amoebozoa. During fruiting body formation nearly 4,000 genes, corresponding to specific pathways required for differentiation processes, are upregulated. A comparison with genes involved in the development of dictyosteliids revealed conservation of >500 genes, but most of them are also present in Acanthamoeba castellanii for which fruiting bodies have not been documented. Moreover, expression regulation of those genes differs between P. aurantium and Dictyostelium discoideum. Within Amoebozoa differentiation to fruiting bodies is common, but our current genome analysis suggests that protosteliids and dictyosteliids used different routes to achieve this. Most remarkable is both the large repertoire and diversity between species in genes that mediate environmental sensing and signal processing. This likely reflects an immense adaptability of the single cell stage to varying environmental conditions. We surmise that this signaling repertoire provided sufficient building blocks to accommodate the relatively simple demands for cell-cell communication in the early multicellular forms.}, } @article {pmid29377633, year = {2018}, author = {Flowers, JJ and Richards, MA and Baliga, N and Meyer, B and Stahl, DA}, title = {Constraint-based modelling captures the metabolic versatility of Desulfovibrio vulgaris.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {190-201}, doi = {10.1111/1758-2229.12619}, pmid = {29377633}, issn = {1758-2229}, mesh = {Bacterial Proteins/genetics/metabolism ; Desulfovibrio vulgaris/genetics/*metabolism ; Electron Transport ; Models, Biological ; Mutation ; Oxidation-Reduction ; Sulfates/metabolism ; }, abstract = {A refined Desulfovibrio vulgaris Hildenborough flux balance analysis (FBA) model (iJF744) was developed, incorporating 1016 reactions that include 744 genes and 951 metabolites. A draft model was first developed through automatic model reconstruction using the ModelSeed Server and then curated based on existing literature. The curated model was further refined by incorporating three recently proposed redox reactions involving the Hdr-Flx and Qmo complexes and a lactate dehydrogenase (LdhAB, DVU 3027-3028) indicated by mutation and transcript analyses to serve electron transfer reactions central to syntrophic and respiratory growth. Eight different variations of this model were evaluated by comparing model predictions to experimental data determined for four different growth conditions - three for sulfate respiration (with lactate, pyruvate or H2 /CO2 -acetate) and one for fermentation in syntrophic coculture. The final general model supports (i) a role for Hdr-Flx in the oxidation of DsrC and ferredoxin, and reduction of NAD+ in a flavin-based electron confurcating reaction sequence, (ii) a function of the Qmo complex in receiving electrons from the menaquinone pool and potentially from ferredoxin to reduce APS and (iii) a reduction of the soluble DsrC by LdhAB and a function of DsrC in electron transfer reactions other than sulfite reduction.}, } @article {pmid29377623, year = {2018}, author = {Morales, SE and Meyer, M and Currie, K and Baltar, F}, title = {Are oceanic fronts ecotones? Seasonal changes along the subtropical front show fronts as bacterioplankton transition zones but not diversity hotspots.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {184-189}, doi = {10.1111/1758-2229.12618}, pmid = {29377623}, issn = {1758-2229}, mesh = {Bacteria/classification/genetics/*isolation & purification ; *Biodiversity ; DNA, Bacterial/genetics ; New Zealand ; Oceans and Seas ; Phylogeny ; Plankton/classification/genetics/*isolation & purification ; RNA, Ribosomal, 16S/genetics ; Seasons ; Seawater/*microbiology ; }, abstract = {Ecotones are regarded as diversity hotspots in terrestrial systems, but it is unknown if this 'ecotone effect' occurs in the marine environment. Oceanic fronts are widespread mesoscale features, present in the boundary between different water masses, and are arguably the best potential examples of ecotones in the ocean. Here we performed the first seasonal study along an oceanic front, combining 16S rRNA gene sequencing coupled with a high spatial resolution analysis of the physical properties of the water masses. Using the Subtropical Frontal Zone off New Zealand we demonstrate that fronts delimit shifts in bacterioplankton community composition between water masses, but that the strength of this effect is seasonally dependent. While creating a transition zone where physicochemical parameters and bacterioplankton communities get mixed, this ecotone does not result in increased diversity. Thus unlike terrestrial ecotones, oceanic fronts are boundaries but not hotspots of bacterioplankton diversity in the ocean.}, } @article {pmid29377607, year = {2018}, author = {Bolourian, A and Mojtahedi, Z}, title = {Immunosuppressants produced by Streptomyces: evolution, hygiene hypothesis, tumour rapalog resistance and probiotics.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {123-126}, doi = {10.1111/1758-2229.12617}, pmid = {29377607}, issn = {1758-2229}, mesh = {Biological Evolution ; Drug Resistance ; Humans ; *Hygiene Hypothesis ; Immunosuppressive Agents/*metabolism/pharmacology ; Neoplasms/*drug therapy ; Sirolimus/chemistry/metabolism/pharmacology ; Streptomyces/*metabolism ; Tacrolimus/chemistry/metabolism/pharmacology ; }, abstract = {Resistance to a drug and the suppression of inflammatory disorders with immunosuppressive drugs might have happened upon exposure to natural compounds during evolution. Streptomycetes are soil bacteria, but they produce therapeutic drugs. They have been reported to be the low-abundant members of mucosal microbiomes with a higher prevalence in nonhumans ingesting soil compared with humans. Their lower abundance in the human microbiome might be the representations of our current hygienic lifestyle. We suggest that the Streptomyces bacteria producing antiproliferative/immunosuppressive compounds (e.g., rapamycin and tacrolimus) contribute to the rapalog resistance of certain mucosal tumours (e.g., colon cancer) and the 'hygiene hypothesis'. If so, the shortage of exposure to these compounds in the current lifestyle might be an underlying reason for the increase of inflammatory diseases, such as inflammatory bowel diseases (IBD). An investigation on adding certain Streptomycetes (e.g., S. hygroscopicus and S. tubercidicus) to the list of probiotics against inflammatory diseases would be an interesting research area in the future.}, } @article {pmid29377517, year = {2018}, author = {Rummens, K and De Meester, L and Souffreau, C}, title = {Inoculation history affects community composition in experimental freshwater bacterioplankton communities.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1120-1133}, doi = {10.1111/1462-2920.14053}, pmid = {29377517}, issn = {1462-2920}, abstract = {Priority effects occur when the arrival order of species or genotypes has a lasting effect on community or population structure. For freshwater bacteria, priority effects have been shown experimentally among individual species, but no experiments have been performed using complex natural communities. We investigated experimentally whether a foreign bacterioplankton community influences the community assembly trajectory when inoculated prior to the local community, whether inoculation time lag affects priority effects, and how the individual OTUs responded to time lag. Two bacterioplankton communities from dissimilar ponds were inoculated into one of the natural media with a time lag of 0, 12, 36 or 60 h, giving advantage in time to the foreign community. All three time lags resulted in priority effects, as the final community composition of these treatments differed significantly from that of the treatment with no time lag, but compositional shifts were not linear to inoculation time lag. The responses of individual OTUs to time lag were highly diverse and not predictable based on their immigration history or relative abundance in the inocula or control. The observed impact and complexity of priority effects in multispecies systems emphasize the importance of this process in structuring both natural and industrial bacterial communities.}, } @article {pmid29375807, year = {2018}, author = {Gélin, P and Fauvelot, C and Bigot, L and Baly, J and Magalon, H}, title = {From population connectivity to the art of striping Russian dolls: the lessons from Pocillopora corals.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1411-1426}, pmid = {29375807}, issn = {2045-7758}, abstract = {Here, we examined the genetic variability in the coral genus Pocillopora, in particular within the Primary Species Hypothesis PSH09, identified by Gélin, Postaire, Fauvelot and Magalon (2017) using species delimitation methods [also named Pocillopora eydouxi/meandrina complex sensu, Schmidt-Roach, Miller, Lundgren, & Andreakis (2014)] and which was found to split into three secondary species hypotheses (SSH09a, SSH09b, and SSH09c) according to assignment tests using multi-locus genotypes (13 microsatellites). From a large sampling (2,507 colonies) achieved in three marine provinces [Western Indian Ocean (WIO), Tropical Southwestern Pacific (TSP), and Southeast Polynesia (SEP)], genetic structuring analysis conducted with two clustering analyses (structure and DAPC) using 13 microsatellites revealed that SSH09a was restricted to the WIO while SSH09b and SSH09c were almost exclusively in the TSP and SEP. More surprisingly, each SSH split into two to three genetically differentiated clusters, found in sympatry at the reef scale, leading to a pattern of nested hierarchical levels (PSH > SSH > cluster), each level hiding highly differentiated genetic groups. Thus, rather than structured populations within a single species, these three SSHs, and even the eight clusters, likely represent distinct genetic lineages engaged in a speciation process or real species. The issue is now to understand which hierarchical level (SSH, cluster, or even below) corresponds to the species one. Several hypotheses are discussed on the processes leading to this pattern of mixed clusters in sympatry, evoking formation of reproductive barriers, either by allopatric speciation or habitat selection.}, } @article {pmid29375806, year = {2018}, author = {Kasagi, S and Mizusawa, K and Takahashi, A}, title = {Green-shifting of SWS2A opsin sensitivity and loss of function of RH2-A opsin in flounders, genus Verasper.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1399-1410}, pmid = {29375806}, issn = {2045-7758}, abstract = {We identified visual opsin genes for three flounder species, including the spotted halibut (Verasper variegatus), slime flounder (Microstomus achne), and Japanese flounder (Paralichthys olivaceus). Structure and function of opsins for the three species were characterized together with those of the barfin flounder (V. moseri) that we previously reported. All four flounder species possessed five basic opsin genes, including lws, sws1, sws2, rh1, and rh2. Specific features were observed in rh2 and sws2. The rh2-a, one of the three subtypes of rh2, was absent in the genome of V. variegatus and pseudogenized in V. moseri. Moreover, rh2-a mRNA was not detected in M. achne and P. olivaceus, despite the presence of a functional reading frame. Analyses of the maximum absorption spectra (λmax) estimated by in vitro reconstitution indicated that SWS2A of M. achne (451.9 nm) and P. olivaceus (465.6 nm) were blue-sensitive, whereas in V. variegatus (485.4 nm), it was green-sensitive and comparable to V. moseri (482.3 nm). Our results indicate that although the four flounder species possess a similar opsin gene repertoire, the SWS2A opsin of the genus Verasper is functionally green-sensitive, while its overall structure remains conserved as a blue-sensitive opsin. Further, the rh2-a function seems to have been reduced during the evolution of flounders. λmax values of predicted ancestral SWS2A of Pleuronectiformes and Pleuronectidae was 465.4 and 462.4 nm, respectively, indicating that these were blue-sensitive. Thus, the green-sensitive SWS2A is estimated to be arisen in ancestral Verasper genus. It is suggested that the sensitivity shift of SWS2A from blue to green may have compensated functional reduction in RH2-A.}, } @article {pmid29375805, year = {2018}, author = {Srinivasan, M and Swannack, TM and Grant, WE and Rajan, J and Würsig, B}, title = {To feed or not to feed? Bioenergetic impacts of fear-driven behaviors in lactating dolphins.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1384-1398}, pmid = {29375805}, issn = {2045-7758}, abstract = {In mammals, lactation can be the most energetically expensive part of the reproductive cycle. Thus, when energy needs are compromised due to predation risk, environmental disturbance, or resource scarcity, future reproductive success can be impacted. In marine and terrestrial environments, foraging behavior is inextricably linked to predation risk. But quantification of foraging energetics for lactating animals under predation risk is less understood. In this study, we used a spatially explicit individual-based model to study how changes in physiology (lactating or not) and the environment (predation risk) affect optimal behavior in dolphins. Specifically, we predicted that an adult dolphin without calf would incur lower relative energetic costs compared to a lactating dolphin with calf regardless of predation risk severity, antipredator behavior, or prey quality consumed. Under this state-dependent analysis of risk approach, we found predation risk to be a stronger driver in affecting total energetic costs (foraging plus locomotor costs) than food quality for both dolphin types. Further, contrary to our hypothesis, after accounting for raised energy demands, a lactating dolphin with calf does not necessarily have higher relative-to-baseline costs than a dolphin without calf. Our results indicate that both a lactating (with calf) and non-lactating dolphin incur lowered energetic costs under a risk-averse behavioral scheme, but consequently suffer from lost foraging calories. A lactating dolphin with calf could be particularly worse off in lost foraging calories under elevated predation risk, heightened vigilance, and increased hiding time relative to an adult dolphin without calf. Further, hiding time in refuge could be more consequential than detection distance for both dolphin types in estimated costs and losses incurred. In conclusion, our study found that reproductive status is an important consideration in analyzing risk effects in mammals, especially in animals with lengthy lactation periods and those exposed to both biological and nonbiological stressors.}, } @article {pmid29375804, year = {2018}, author = {Grunst, ML and Grunst, AS and Formica, VA and Gonser, RA and Tuttle, EM}, title = {Multiple signaling functions of song in a polymorphic species with alternative reproductive strategies.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1369-1383}, pmid = {29375804}, issn = {2045-7758}, support = {R01 GM084229/GM/NIGMS NIH HHS/United States ; }, abstract = {Vocal traits can be sexually selected to reflect male quality, but may also evolve to serve additional signaling functions. We used a long-term dataset to examine the signaling potential of song in dimorphic white-throated sparrows (Zonotrichia albicollis). We investigated whether song conveys multifaceted information about the vocalizing individual, including fitness, species identity, individual identity, and morph. We also evaluated whether song traits correlate differently with fitness in the two morphs, as the more promiscuous strategy of white, relative to tan, morph males might impose stronger sexual selection. Males with high song rates achieved higher lifetime reproductive success, and this pattern was driven by white morph males. In addition, males that sang songs with many notes survived longer, but this pattern was less robust. Thus, song traits reflect differences in fitness and may more strongly affect fitness in the white morph. Song frequency was unrelated to fitness, body size, or morph, but was individual specific and could signal individual identity. Songs of the two morphs displayed similar frequency ratios and bandwidths. However, tan morph males sang songs with longer first notes, fewer notes, and higher variability. Thus, song could be used in morph discrimination. Variation in frequency ratios between notes was low and could function in conspecific recognition, but pitch change dynamics did differ between four different song types observed. Our results support a multiple messages model for white-throated sparrow song, in which different song traits communicate discrete information about the vocalizing individual.}, } @article {pmid29375803, year = {2018}, author = {Thongsripong, P and Chandler, JA and Green, AB and Kittayapong, P and Wilcox, BA and Kapan, DD and Bennett, SN}, title = {Mosquito vector-associated microbiota: Metabarcoding bacteria and eukaryotic symbionts across habitat types in Thailand endemic for dengue and other arthropod-borne diseases.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1352-1368}, pmid = {29375803}, issn = {2045-7758}, support = {P20 RR018727/RR/NCRR NIH HHS/United States ; U54 AI065359/AI/NIAID NIH HHS/United States ; }, abstract = {Vector-borne diseases are a major health burden, yet factors affecting their spread are only partially understood. For example, microbial symbionts can impact mosquito reproduction, survival, and vectorial capacity, and hence affect disease transmission. Nonetheless, current knowledge of mosquito-associated microbial communities is limited. To characterize the bacterial and eukaryotic microbial communities of multiple vector species collected from different habitat types in disease endemic areas, we employed next-generation 454 pyrosequencing of 16S and 18S rRNA amplicon libraries, also known as metabarcoding. We investigated pooled whole adult mosquitoes of three medically important vectors, Aedes aegypti, Ae. albopictus, and Culex quinquefasciatus, collected from different habitats across central Thailand where we previously characterized mosquito diversity. Our results indicate that diversity within the mosquito microbiota is low, with the majority of microbes assigned to one or a few taxa. Two of the most common eukaryotic and bacterial genera recovered (Ascogregarina and Wolbachia, respectively) are known mosquito endosymbionts with potentially parasitic and long evolutionary relationships with their hosts. Patterns of microbial composition and diversity appeared to differ by both vector species and habitat for a given species, although high variability between samples suggests a strong stochastic element to microbiota assembly. In general, our findings suggest that multiple factors, such as habitat condition and mosquito species identity, may influence overall microbial community composition, and thus provide a basis for further investigations into the interactions between vectors, their microbial communities, and human-impacted landscapes that may ultimately affect vector-borne disease risk.}, } @article {pmid29375802, year = {2018}, author = {Kwon, E and English, WB and Weiser, EL and Franks, SE and Hodkinson, DJ and Lank, DB and Sandercock, BK}, title = {Delayed egg-laying and shortened incubation duration of Arctic-breeding shorebirds coincide with climate cooling.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1339-1351}, pmid = {29375802}, issn = {2045-7758}, abstract = {Biological impacts of climate change are exemplified by shifts in phenology. As the timing of breeding advances, the within-season relationships between timing of breeding and reproductive traits may change and cause long-term changes in the population mean value of reproductive traits. We investigated long-term changes in the timing of breeding and within-season patterns of clutch size, egg volume, incubation duration, and daily nest survival of three shorebird species between two decades. Based on previously known within-season patterns and assuming a warming trend, we hypothesized that the timing of clutch initiation would advance between decades and would be coupled with increases in mean clutch size, egg volume, and daily nest survival rate. We monitored 1,378 nests of western sandpipers, semipalmated sandpipers, and red-necked phalaropes at a subarctic site during 1993-1996 and 2010-2014. Sandpipers have biparental incubation, whereas phalaropes have uniparental incubation. We found an unexpected long-term cooling trend during the early part of the breeding season. Three species delayed clutch initiation by 5 days in the 2010s relative to the 1990s. Clutch size and daily nest survival showed strong within-season declines in sandpipers, but not in phalaropes. Egg volume showed strong within-season declines in one species of sandpiper, but increased in phalaropes. Despite the within-season patterns in traits and shifts in phenology, clutch size, egg volume, and daily nest survival were similar between decades. In contrast, incubation duration did not show within-season variation, but decreased by 2 days in sandpipers and increased by 2 days in phalaropes. Shorebirds demonstrated variable breeding phenology and incubation duration in relation to climate cooling, but little change in nonphenological components of traits. Our results indicate that the breeding phenology of shorebirds is closely associated with the temperature conditions on breeding ground, the effects of which can vary among reproductive traits and among sympatric species.}, } @article {pmid29375801, year = {2018}, author = {Barnas, A and Newman, R and Felege, CJ and Corcoran, MP and Hervey, SD and Stechmann, TJ and Rockwell, RF and Ellis-Felege, SN}, title = {Evaluating behavioral responses of nesting lesser snow geese to unmanned aircraft surveys.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1328-1338}, pmid = {29375801}, issn = {2045-7758}, abstract = {Unmanned aircraft systems (UAS) are relatively new technologies gaining popularity among wildlife biologists. As with any new tool in wildlife science, operating protocols must be developed through rigorous protocol testing. Few studies have been conducted that quantify the impacts UAS may have on unhabituated individuals in the wild using standard aerial survey protocols. We evaluated impacts of unmanned surveys by measuring UAS-induced behavioral responses during the nesting phase of lesser snow geese (Anser caerulescens caerulescens) in Wapusk National Park, Manitoba, Canada. We conducted surveys with a fixed-wing Trimble UX5 and monitored behavioral changes via discreet surveillance cameras at 25 nests. Days with UAS surveys resulted in decreased resting and increased nest maintenance, low scanning, high scanning, head-cocking and off-nest behaviors when compared to days without UAS surveys. In the group of birds flown over, head-cocking for overhead vigilance was rarely seen prior to launch or after landing (mean estimates 0.03% and 0.02%, respectively) but increased to 0.56% of the time when the aircraft was flying overhead suggesting that birds were able to detect the aircraft during flight. Neither UAS survey altitude nor launch distance alone in this study was strong predictors of nesting behaviors, although our flight altitudes (≥75 m above ground level) were much higher than previously published behavioral studies. Synthesis and applications: The diversity of UAS models makes generalizations on behavioral impacts difficult, and we caution that researchers should design UAS studies with knowledge that some minimal disturbance is likely to occur. We recommend flight designs take potential behavioral impacts into account by increasing survey altitude where data quality requirements permit. Such flight designs should consider a priori knowledge of focal species' behavioral characteristics. Research is needed to determine whether any such disturbance is a result of visual or auditory stimuli.}, } @article {pmid29375800, year = {2018}, author = {Sheridan, JA and Caruso, NM and Apodaca, JJ and Rissler, LJ}, title = {Shifts in frog size and phenology: Testing predictions of climate change on a widespread anuran using data from prior to rapid climate warming.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1316-1327}, pmid = {29375800}, issn = {2045-7758}, abstract = {Changes in body size and breeding phenology have been identified as two major ecological consequences of climate change, yet it remains unclear whether climate acts directly or indirectly on these variables. To better understand the relationship between climate and ecological changes, it is necessary to determine environmental predictors of both size and phenology using data from prior to the onset of rapid climate warming, and then to examine spatially explicit changes in climate, size, and phenology, not just general spatial and temporal trends. We used 100 years of natural history collection data for the wood frog, Lithobates sylvaticus with a range >9 million km2, and spatially explicit environmental data to determine the best predictors of size and phenology prior to rapid climate warming (1901-1960). We then tested how closely size and phenology changes predicted by those environmental variables reflected actual changes from 1961 to 2000. Size, phenology, and climate all changed as expected (smaller, earlier, and warmer, respectively) at broad spatial scales across the entire study range. However, while spatially explicit changes in climate variables accurately predicted changes in phenology, they did not accurately predict size changes during recent climate change (1961-2000), contrary to expectations from numerous recent studies. Our results suggest that changes in climate are directly linked to observed phenological shifts. However, the mechanisms driving observed body size changes are yet to be determined, given the less straightforward relationship between size and climate factors examined in this study. We recommend that caution be used in "space-for-time" studies where measures of a species' traits at lower latitudes or elevations are considered representative of those under future projected climate conditions. Future studies should aim to determine mechanisms driving trends in phenology and body size, as well as the impact of climate on population density, which may influence body size.}, } @article {pmid29375799, year = {2018}, author = {Nicholls, JA and Schönrogge, K and Preuss, S and Stone, GN}, title = {Partitioning of herbivore hosts across time and food plants promotes diversification in the Megastigmus dorsalis oak gall parasitoid complex.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1300-1315}, pmid = {29375799}, issn = {2045-7758}, abstract = {Communities of insect herbivores and their natural enemies are rich and ecologically crucial components of terrestrial biodiversity. Understanding the processes that promote their origin and maintenance is thus of considerable interest. One major proposed mechanism is ecological speciation through host-associated differentiation (HAD), the divergence of a polyphagous species first into ecological host races and eventually into more specialized daughter species. The rich chalcid parasitoid communities attacking cynipid oak gall wasp hosts are structured by multiple host traits, including food plant taxon, host gall phenology, and gall structure. Here, we ask whether the same traits structure genetic diversity within supposedly generalist parasitoid morphospecies. We use mitochondrial DNA sequences and microsatellite genotypes to quantify HAD for Megastigmus (Bootanomyia) dorsalis, a complex of two apparently generalist cryptic parasitoid species attacking oak galls. Ancient Balkan refugial populations showed phenological separation between the cryptic species, one primarily attacking spring galls, and the other mainly attacking autumn galls. The spring species also contained host races specializing on galls developing on different host-plant lineages (sections Cerris vs. Quercus) within the oak genus Quercus. These results indicate more significant host-associated structuring within oak gall parasitoid communities than previously thought and support ecological theory predicting the evolution of specialist lineages within generalist parasitoids. In contrast, UK populations of the autumn cryptic species associated with both native and recently invading oak gall wasps showed no evidence of population differentiation, implying rapid recruitment of native parasitoid populations onto invading hosts, and hence potential for natural biological control. This is of significance given recent rapid range expansion of the economically damaging chestnut gall wasp, Dryocosmus kuriphilus, in Europe.}, } @article {pmid29375798, year = {2018}, author = {Morozov, S and Leinonen, T and Merilä, J and McCairns, RJS}, title = {Selection on the morphology-physiology-performance nexus: Lessons from freshwater stickleback morphs.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1286-1299}, pmid = {29375798}, issn = {2045-7758}, abstract = {Conspecifics inhabiting divergent environments frequently differ in morphology, physiology, and performance, but the interrelationships amongst traits and with Darwinian fitness remains poorly understood. We investigated population differentiation in morphology, metabolic rate, and swimming performance in three-spined sticklebacks (Gasterosteus aculeatus L.), contrasting a marine/ancestral population with two distinct freshwater morphotypes derived from it: the "typical" low-plated morph, and a unique "small-plated" morph. We test the hypothesis that similar to plate loss in other freshwater populations, reduction in lateral plate size also evolved in response to selection. Additionally, we test how morphology, physiology, and performance have evolved in concert as a response to differences in selection between marine and freshwater environments. We raised pure-bred second-generation fish originating from three populations and quantified their lateral plate coverage, burst- and critical swimming speeds, as well as standard and active metabolic rates. Using a multivariate QST-FST framework, we detected signals of directional selection on metabolic physiology and lateral plate coverage, notably demonstrating that selection is responsible for the reduction in lateral plate coverage in a small-plated stickleback population. We also uncovered signals of multivariate selection amongst all bivariate trait combinations except the two metrics of swimming performance. Divergence between the freshwater and marine populations exceeded neutral expectation in morphology and in most physiological and performance traits, indicating that adaptation to freshwater habitats has occurred, but through different combinations of traits in different populations. These results highlight both the complex interplay between morphology, physiology and performance in local adaptation, and a framework for their investigation.}, } @article {pmid29375797, year = {2018}, author = {Tong, GX and Xu, W and Zhang, YQ and Zhang, QY and Yin, JS and Kuang, YY}, title = {De novo assembly and characterization of the Hucho taimen transcriptome.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1271-1285}, pmid = {29375797}, issn = {2045-7758}, abstract = {Taimen (Hucho taimen) is an important ecological and economic species that is classified as vulnerable by the IUCN Red List of Threatened Species; however, limited genomic information is available on this species. RNA-Seq is a useful tool for obtaining genetic information and developing genetic markers for nonmodel species in addition to its application in gene expression profiling. In this study, we performed a comprehensive RNA-Seq analysis of taimen. We obtained 157 M clean reads (14.7 Gb) and used them to de novo assemble a high-quality transcriptome with a N50 size of 1,060 bp. In the assembly, 82% of the transcripts were annotated using several databases, and 14,666 of the transcripts contained a full open reading frame. The assembly covered 75% of the transcripts of Atlantic salmon and 57.3% of the protein-coding genes of rainbow trout. To learn about the genome evolution, we performed a systematic comparative analysis across 11 teleosts including eight salmonids and found 313 unique gene families in taimen. Using Atlantic salmon and rainbow trout transcriptomes as the background, we identified 250 positive selection transcripts. The pathway enrichment analysis revealed a unique characteristic of taimen: It possesses more immune-related genes than Atlantic salmon and rainbow trout; moreover, some genes have undergone strong positive selection. We also developed a pipeline for identifying microsatellite marker genotypes in samples and successfully identified 24 polymorphic microsatellite markers for taimen. These data and tools are useful for studying conservation genetics, phylogenetics, evolution among salmonids, and selective breeding for threatened taimen.}, } @article {pmid29375796, year = {2018}, author = {Zhang, QP and Hu, WF and Zhou, TT and Kong, SS and Liu, ZF and Zheng, RQ}, title = {Interspecies introgressive hybridization in spiny frogs Quasipaa (Family Dicroglossidae) revealed by analyses on multiple mitochondrial and nuclear genes.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1260-1270}, pmid = {29375796}, issn = {2045-7758}, abstract = {Introgression may lead to discordant patterns of variation among loci and traits. For example, previous phylogeographic studies on the genus Quasipaa detected signs of genetic introgression from genetically and morphologically divergent Quasipaa shini or Quasipaa spinosa. In this study, we used mitochondrial and nuclear DNA sequence data to verify the widespread introgressive hybridization in the closely related species of the genus Quasipaa, evaluate the level of genetic diversity, and reveal the formation mechanism of introgressive hybridization. In Longsheng, Guangxi Province, signs of asymmetrical nuclear introgression were detected between Quasipaa boulengeri and Q. shini. Unidirectional mitochondrial introgression was revealed from Q. spinosa to Q. shini. By contrast, bidirectional mitochondrial gene introgression was detected between Q. spinosa and Q. shini in Lushan, Jiangxi Province. Our study also detected ancient hybridizations between a female Q. spinosa and a male Q. jiulongensis in Zhejiang Province. Analyses on mitochondrial and nuclear genes verified three candidate cryptic species in Q. spinosa, and a cryptic species may also exist in Q. boulengeri. However, no evidence of introgressive hybridization was found between Q. spinosa and Q. boulengeri. Quasipaa exilispinosa from all the sampling localities appeared to be deeply divergent from other communities. Our results suggest widespread introgressive hybridization in closely related species of Quasipaa and provide a fundamental basis for illumination of the forming mechanism of introgressive hybridization, classification of species, and biodiversity assessment in Quasipaa.}, } @article {pmid29375795, year = {2018}, author = {Mehrparvar, M and Zytynska, SE and Balog, A and Weisser, WW}, title = {Coexistence through mutualist-dependent reversal of competitive hierarchies.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1247-1259}, pmid = {29375795}, issn = {2045-7758}, abstract = {Mechanisms that allow for the coexistence of two competing species that share a trophic level can be broadly divided into those that prevent competitive exclusion of one species within a local area, and those that allow for coexistence only at a regional level. While the presence of aphid-tending ants can change the distribution of aphids among host plants, the role of mutualistic ants has not been fully explored to understand coexistence of multiple aphid species in a community. The tansy plant (Tanacetum vulgare) hosts three common and specialized aphid species, with only one being tended by ants. Often, these aphids species will not coexist on the same plant but will coexist across multiple plant hosts in a field. In this study, we aim to understand how interactions with mutualistic ants and predators affect the coexistence of multiple species of aphid herbivores on tansy. We show that the presence of ants drives community assembly at the level of individual plant, that is, the local community, by favoring one ant-tended species, Metopeurum fuscoviride, while preying on the untended Macrosiphoniella tanacetaria and, to a lesser extent, Uroleucon tanaceti. Competitive hierarchies without ants were very different from those with ants. At the regional level, multiple tansy plants provide a habitat across which all aphid species can coexist at the larger spatial scale, while being competitively excluded at the local scale. In this case, ant mutualist-dependent reversal of the competitive hierarchy can drive community dynamics in a plant-aphid system.}, } @article {pmid29375794, year = {2018}, author = {Kawatsu, K}, title = {Ecological effects of sex differ with trophic positions in a simple food web.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1239-1246}, pmid = {29375794}, issn = {2045-7758}, abstract = {Sexual differences in parental investment, predation pressure, and foraging efforts are common in nature and affect the trophic flow in food webs. Specifically, the sexual differences in predator and prey behavior change in trophic inflow and outflow, respectively, while those in parental investment alter the reproductive allocation of acquired resources in the population. Consequently, these factors may play an important role in determining the system structure and persistence. However, few studies have examined how sexual differences in trophic flow affect food web dynamics. In this study, I show the ecological role of sex by explicitly incorporating sexual differences in trophic flow into a three-species food web model. The results demonstrated that the ecological waste of males, that is, the amount of trophic inflow into males with less parental investment, plays an important role in system persistence and structure. In particular, the synergy between sexual differences in parental investment and trophic inflows and outflows is important in determining web persistence: Significant impacts of male-biased trophic flows require the condition of anisogamy. In addition, the dynamic effects of the ecological waste of males differ with trophic level: The coexistence of a food web occurs more frequently with biased inflows into predator males, but occurs less frequently with biased inflows into consumer males. The model analysis indicates that investigating the pattern of sexual differences among trophic positions can enrich our understanding of food web persistence and structure in the real world.}, } @article {pmid29375793, year = {2018}, author = {Matthews, AE and Larkin, JL and Raybuck, DW and Slevin, MC and Stoleson, SH and Boves, TJ}, title = {Feather mite abundance varies but symbiotic nature of mite-host relationship does not differ between two ecologically dissimilar warblers.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1227-1238}, pmid = {29375793}, issn = {2045-7758}, abstract = {Feather mites are obligatory ectosymbionts of birds that primarily feed on the oily secretions from the uropygial gland. Feather mite abundance varies within and among host species and has various effects on host condition and fitness, but there is little consensus on factors that drive variation of this symbiotic system. We tested hypotheses regarding how within-species and among-species traits explain variation in both (1) mite abundance and (2) relationships between mite abundance and host body condition and components of host fitness (reproductive performance and apparent annual survival). We focused on two closely related (Parulidae), but ecologically distinct, species: Setophaga cerulea (Cerulean Warbler), a canopy dwelling open-cup nester, and Protonotaria citrea (Prothonotary Warbler), an understory dwelling, cavity nester. We predicted that feather mites would be more abundant on and have a more parasitic relationship with P. citrea, and within P. citrea, females and older individuals would harbor greater mite abundances. We captured, took body measurements, quantified feather mite abundance on individuals' primaries and rectrices, and monitored individuals and their nests to estimate fitness. Feather mite abundance differed by species, but in the opposite direction of our prediction. There was no relationship between mite abundance and any measure of body condition or fitness for either species or sex (also contrary to our predictions). Our results suggest that species biology and ecological context may influence mite abundance on hosts. However, this pattern does not extend to differential effects of mites on measures of host body condition or fitness.}, } @article {pmid29375792, year = {2018}, author = {Nolet, P and Kneeshaw, D and Messier, C and Béland, M}, title = {Comparing the effects of even- and uneven-aged silviculture on ecological diversity and processes: A review.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1217-1226}, pmid = {29375792}, issn = {2045-7758}, abstract = {With an increasing pressure on forested landscapes, conservation areas may fail to maintain biodiversity if they are not supported by the surrounding managed forest matrix. Worldwide, forests are managed by one of two broad approaches-even- and uneven-aged silviculture. In recent decades, there has been rising public pressure against the systematic use of even-aged silviculture (especially clear-cutting) because of its perceived negative esthetic and ecological impacts. This led to an increased interest for uneven-aged silviculture. However, to date, there has been no worldwide ecological comparison of the two approaches, based on multiple indicators. Overall, for the 99 combinations of properties or processes verified (one study may have evaluated more than one property or process), we found nineteen (23) combinations that clearly showed uneven-aged silviculture improved the evaluated metrics compared to even-aged silviculture, eleven (16) combinations that showed the opposite, and 60 combinations that were equivocal. Furthermore, many studies were based on a limited study design without either a timescale (44 of the 76) or spatial (54 of the 76) scale consideration. Current views that uneven-aged silviculture is better suited than even-aged silviculture for maintaining ecological diversity and processes are not substantiated by our analyses. Our review, by studying a large range of indicators and many different taxonomic groups, also clearly demonstrates that no single approach can be relied on and that both approaches are needed to ensure a greater number of positive impacts. Moreover, the review clearly highlights the importance of maintaining protected areas as some taxonomic groups were found to be negatively affected no matter the management approach used. Finally, our review points to a lack of knowledge for determining the use of even- or uneven-aged silviculture in terms of both their respective proportion in the landscape and their spatial agency.}, } @article {pmid29375791, year = {2018}, author = {Schrago, CG and Mello, B and Pereira, AG and Furtado, C and Seuánez, HN}, title = {Impact of long-term chromosomal shuffling on the multispecies coalescent analysis of two anthropoid primate lineages.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1206-1216}, pmid = {29375791}, issn = {2045-7758}, abstract = {Multispecies coalescent (MSC) theory assumes that gene trees inferred from individual loci are independent trials of the MSC process. As genes might be physically close in syntenic associations spanning along chromosome regions, these assumptions might be flawed in evolutionary lineages with substantial karyotypic shuffling. Neotropical primates (NP) represent an ideal case for assessing the performance of MSC methods in such scenarios because chromosome diploid number varies significantly in this lineage. To this end, we investigated the effect of sequence length on the theoretical expectations of MSC model, as well as the results of coalescent-based tree inference methods. This was carried out by comparing NP with hominids, a lineage in which chromosome macrostructure has been stable for at least 15 million years. We found that departure from the MSC model in Neotropical primates decreased with smaller sequence fragments, where sites sharing the same evolutionary history were more frequently found than in longer fragments. This scenario probably resulted from extensive karyotypic rearrangement occurring during the radiation of NP, contrary to the comparatively stable chromosome evolution in hominids.}, } @article {pmid29375790, year = {2018}, author = {Reese, AT and Lulow, K and David, LA and Wright, JP}, title = {Plant community and soil conditions individually affect soil microbial community assembly in experimental mesocosms.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1196-1205}, pmid = {29375790}, issn = {2045-7758}, abstract = {Soils harbor large, diverse microbial communities critical for local and global ecosystem functioning that are controlled by multiple and poorly understood processes. In particular, while there is observational evidence of relationships between both biotic and abiotic conditions and microbial composition and diversity, there have been few experimental tests to determine the relative importance of these two sets of factors at local scales. Here, we report the results of a fully factorial experiment manipulating soil conditions and plant cover on old-field mesocosms across a latitudinal gradient. The largest contributor to beta diversity was site-to-site variation, but, having corrected for that, we observed significant effects of both plant and soil treatments on microbial composition. Separate phyla were associated with each treatment type, and no interactions between soil and plant treatment were observed. Individual soil characteristics and biotic parameters were also associated with overall beta-diversity patterns and phyla abundance. In contrast, soil microbial diversity was only associated with site and not experimental treatment. Overall, plant community treatment explained more variation than soil treatment, a result not previously appreciated because it is difficult to dissociate plant community composition and soil conditions in observational studies across gradients. This work highlights the need for more nuanced, multifactorial experiments in microbial ecology and in particular indicates a greater focus on relationships between plant composition and microbial composition during community assembly.}, } @article {pmid29375789, year = {2018}, author = {Garzón-Orduña, IJ and Brower, AVZ}, title = {Quantified reproductive isolation in Heliconius butterflies: Implications for introgression and hybrid speciation.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1186-1195}, pmid = {29375789}, issn = {2045-7758}, abstract = {Heliconius butterflies have become a model for the study of speciation with gene flow. For adaptive introgression to take place, there must be incomplete barriers to gene exchange that allow interspecific hybridization and multiple generations of backcrossing. The recent publication of estimates of individual components of reproductive isolation between several species of butterflies in the Heliconius melpomene-H. cydno clade allowed us to calculate total reproductive isolation estimates for these species. According to these estimates, the butterflies are not as promiscuous as has been implied. Differences between species are maintained by intrinsic mechanisms, while reproductive isolation of geographical races within species is mainly due to allopatry. We discuss the implications of this strong isolation for basic aspects of the hybrid speciation with introgression hypothesis.}, } @article {pmid29375788, year = {2018}, author = {Latif, QS and Ellis, MM and Saab, VA and Mellen-McLean, K}, title = {Simulations inform design of regional occupancy-based monitoring for a sparsely distributed, territorial species.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1171-1185}, pmid = {29375788}, issn = {2045-7758}, abstract = {Sparsely distributed species attract conservation concern, but insufficient information on population trends challenges conservation and funding prioritization. Occupancy-based monitoring is attractive for these species, but appropriate sampling design and inference depend on particulars of the study system. We employed spatially explicit simulations to identify minimum levels of sampling effort for a regional occupancy monitoring study design, using white-headed woodpeckers (Picoides albolvartus), a sparsely distributed, territorial species threatened by habitat decline and degradation, as a case study. We compared the original design with commonly proposed alternatives with varying targets of inference (i.e., species range, space use, or abundance) and spatial extent of sampling. Sampling effort needed to achieve adequate power to observe a long-term population trend (≥80% chance to observe a 2% yearly decline over 20 years) with the previously used study design consisted of annually monitoring ≥120 transects using a single-survey approach or ≥90 transects surveyed twice per year using a repeat-survey approach. Designs that shifted inference toward finer-resolution trends in abundance and extended the spatial extent of sampling by shortening transects, employing a single-survey approach to monitoring, and incorporating a panel design (33% of units surveyed per year) improved power and reduced error in estimating abundance trends. In contrast, efforts to monitor coarse-scale trends in species range or space use with repeat surveys provided extremely limited statistical power. Synthesis and applications. Sampling resolutions that approximate home range size, spatially extensive sampling, and designs that target inference of abundance trends rather than range dynamics are probably best suited and most feasible for broad-scale occupancy-based monitoring of sparsely distributed territorial animal species.}, } @article {pmid29375787, year = {2018}, author = {Nakahara, T and Fukano, Y and Hirota, SK and Yahara, T}, title = {Size advantage for male function and size-dependent sex allocation in Ambrosia artemisiifolia, a wind-pollinated plant.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1159-1170}, pmid = {29375787}, issn = {2045-7758}, abstract = {In wind-pollinated plants, male-biased sex allocation is often positively associated with plant size and height. However, effects of size (biomass or reproductive investment) and height were not separated in most previous studies. Here, using experimental populations of monoecious plants, Ambrosia altemisiifolia, we examined (1) how male and female reproductive investments (MRI and FRI) change with biomass and height, (2) how MRI and height affect male reproductive success (MRS) and pollen dispersal, and (3) how height affects seed production. Pollen dispersal kernel and selection gradients on MRS were estimated by 2,102 seeds using six microsatellite markers. First, MRI increased with height, but FRI did not, suggesting that sex allocation is more male-biased with increasing plant height. On the other hand, both MRI and FRI increased with biomass but often more greatly for FRI, and consequently, sex allocation was often female-biased with biomass. Second, MRS increased with both height and MRI, the latter having the same or larger effect on MRS. Estimated pollen dispersal kernel was fat-tailed, with the maximum distance between mates tending to increase with MRI but not with height. Third, the number of seeds did not increase with height. Those findings showed that the male-biased sex allocation in taller plants of A. artemisiifolia is explained by a direct effect of height on MRS.}, } @article {pmid29375786, year = {2018}, author = {Bucher, SF and König, P and Menzel, A and Migliavacca, M and Ewald, J and Römermann, C}, title = {Traits and climate are associated with first flowering day in herbaceous species along elevational gradients.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1147-1158}, pmid = {29375786}, issn = {2045-7758}, abstract = {Phenological responses to changing temperatures are known as "fingerprints of climate change," yet these reactions are highly species specific. To assess whether different plant characteristics are related to these species-specific responses in flowering phenology, we observed the first flowering day (FFD) of ten herbaceous species along two elevational gradients, representing temperature gradients. On the same populations, we measured traits being associated with (1) plant performance (specific leaf area), (2) leaf biochemistry (leaf C, N, P, K, and Mg content), and (3) water-use efficiency (stomatal pore area index and stable carbon isotopes concentration). We found that as elevation increased, FFD was delayed for all species with a highly species-specific rate. Populations at higher elevations needed less temperature accumulation to start flowering than populations of the same species at lower elevations. Surprisingly, traits explained a higher proportion of variance in the phenological data than elevation. Earlier flowering was associated with higher water-use efficiency, higher leaf C, and lower leaf P content. In addition to that, the intensity of shifts in FFD was related to leaf N and K. These results propose that traits have a high potential in explaining phenological variations, which even surpassed the effect of temperature changes in our study. Therefore, they have a high potential to be included in future analyses studying the effects of climate change and will help to improve predictions of vegetation changes.}, } @article {pmid29375785, year = {2018}, author = {Niu, YT and Ye, JF and Zhang, JL and Wan, JZ and Yang, T and Wei, XX and Lu, LM and Li, JH and Chen, ZD}, title = {Long-distance dispersal or postglacial contraction? Insights into disjunction between Himalaya-Hengduan Mountains and Taiwan in a cold-adapted herbaceous genus, Triplostegia.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1131-1146}, pmid = {29375785}, issn = {2045-7758}, abstract = {Current disjunct patterns can result from long-distance dispersal or postglacial contraction. We herein investigate the evolutionary history of Triplostegia to elucidate the disjunction between the Himalaya-Hengduan Mountain region (HHM) and Taiwan (TW). Genetic structure of Triplostegia was investigated for 48 populations using sequences from five chloroplast loci and the ribosomal nuclear internal transcribed spacer. Divergence time estimation, ancestral area reconstruction, and species distribution modeling (SDM) were employed to examine the biogeographic history of Triplostegia. Substantial genetic differentiation among populations from southwestern China (SW), Central China (CC), and TW was detected. Triplostegia was inferred to have originated in SW, and diversification began during the late Miocene; CC was colonized in the mid-Pliocene, and TW was finally colonized in the early Pleistocene. SDM suggested an expansion of climatically suitable areas during the Last Glacial Maximum and range contraction during the Last interglacial in Triplostegia. Disjunction between HHM and TW in Triplostegia is most likely the consequence of topographic isolation and postglacial contraction. The potential climatic suitability areas for Triplostegia by 2070s (2061-2080) are predicted to slightly shrink and move northward. With continued global warming and human-induced deforestation, extinction risk may increase for the cold-adapted species, and appropriate strategies should be employed for ecosystem conservation.}, } @article {pmid29375784, year = {2018}, author = {Wam, HK and Felton, AM and Stolter, C and Nybakken, L and Hjeljord, O}, title = {Moose selecting for specific nutritional composition of birch places limits on food acceptability.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1117-1130}, pmid = {29375784}, issn = {2045-7758}, abstract = {Despite decades of intense research, it remains largely unsolved which nutritional factors underpin food selection by large herbivores in the wild. We measured nutritional composition of birch foliage (Betula pubescens) available to, and used by, moose (Alces alces) in natural settings in two neighboring regions with contrasting animal body mass. This readily available food source is a staple food item in the diet of moose in the high-fitness region, but apparently underutilized by moose in the low-fitness region. Available birch foliage in the two regions had similar concentrations of macronutrients (crude protein [CP], fiber fractions, and water-soluble carbohydrates [WSC]), although a notably lower variation of WSC in the low-fitness region. For minerals, there were several area differences: available birch foliage in the low-fitness region had less Mg (depending on year) and P, but more Ca, Zn, Cu, and Mn. It also had higher concentrations of some plant secondary metabolites: chlorogenic acids, quercetins, and especially MeOH-soluble condensed tannins. Despite the area differences in available foliage, we found the same nutritional composition of birch foliage used in the two regions. Compared to available birch foliage, moose consistently used birch foliage with more CP, more structural fiber (mainly hemicellulose), less WSC, higher concentrations of several minerals (Ca, Zn, K, Mn, Cu), and lower concentrations of some secondary metabolites (most importantly, MeOH-soluble condensed tannins). Our study conceptually supports the nutrient-balancing hypothesis for a large herbivore: within a given temporal frame, moose select for plant material that matches a specific nutritional composition. As our data illustrate, different moose populations may select for the same composition even when the nutritional composition available in a given food source varies between their living areas. Such fastidiousness limits the proportion of available food that is acceptable to the animal and has bearings on our understanding and application of the concept of carrying capacity.}, } @article {pmid29375783, year = {2018}, author = {Jiang, F and Xun, Y and Cai, H and Jin, G}, title = {What factors potentially influence the ability of phylogenetic distance to predict trait dispersion in a temperate forest?.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1107-1116}, pmid = {29375783}, issn = {2045-7758}, abstract = {Although phylogenetic-based approaches have been frequently used to infer ecological processes, they have been increasingly criticized in recent years. To date, the factors that affect phylogenetic signals and further the ability of phylogenetic distance to predict trait dispersion have been assumed but not empirically tested. Therefore, we investigate which factors potentially influence the ability of phylogenetic distance to predict trait dispersion. We quantified the phylogenetic and trait dispersions across size classes and spatial scales in a 9-ha old-growth temperate forest dynamics plot in northeastern China. Phylogenetic signals at the community level were generally lower than those at the species pool level, and phylogenetically clustered communities showed lower phylogenetic signals than did overdispersed communities. This pattern might explain the other three findings of our study. First, phylogenetically overdispersed communities performed better at predicting trait dispersion than did clustered communities. Second, the mean pairwise distance (MPD)-based metric exhibited a stronger correlation with trait dispersion than did the mean nearest taxon distance (MNTD)-based metric. Finally, the MNTD-based metric showed that the prediction accuracy for trait dispersion decreased with increasing spatial scales, whereas its effects were weak on the MPD-based metric. In addition, phylogeny could not determine the dispersions of all functional axes but was able to predict certain traits depending on whether they were evolutionarily conserved. These results were conserved when we removed the effects of space and environment. Our findings highlighted that using phylogenetic distance as a proxy of trait similarity might work in a temperate forest depending on the species in local communities sampled from total pool as well as the traits measured. Utilizing these rules, we should rethink the conclusions of previous studies that were based on phylogenetic-based approaches.}, } @article {pmid29375782, year = {2018}, author = {Lebel, M and Obolski, U and Hadany, L and Sapir, Y}, title = {Pollinator-mediated selection on floral size and tube color in Linum pubescens: Can differential behavior and preference in different times of the day maintain dimorphism?.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1096-1106}, pmid = {29375782}, issn = {2045-7758}, abstract = {Diversity of flower traits is often proposed as the outcome of selection exerted by pollinators. Positive directional pollinator-mediated selection on floral size has been widely shown to reduce phenotypic variance. However, the underlying mechanism of maintaining within-population floral color polymorphism is poorly understood. Divergent selection, mediated by different pollinators or by both mutualists and antagonists, may create and maintain such polymorphism, but it has rarely been shown to result from differential behavior of one pollinator. We tested whether different behaviors of the same pollinators in morning and evening are associated with dimorphic floral trait in Linum pubescens, a Mediterranean annual plant that exhibits variable within-population frequencies of dark- and light-colored flower tubes. Usia bicolor bee-flies, the major pollinators of L. pubescens, are mostly feeding in the flower in the morning, while in the evening they are mostly visiting the flowers for mating. In 2 years of studying L. pubescens in a single large population in the Carmel, Israel, we found in one year that dark-centered flowers received significantly higher fraction of visits in the morning. Fitness was positively affected by number of visits, but no fitness differences were found between tube-color morphs, suggesting that both morphs have similar pollination success. Using mediation analysis, we found that flower size was under positive directional pollinator-mediated selection in both years, but pollinator behavior did not explain entirely this selection, which was possibly mediated also by other agents, such as florivores or a-biotic stresses. While most pollinator-mediated selection studies show that flower size signals food reward, in L. pubescens, it may also signal for mating place, which may drive positive selection. While flower size found to be under pollinator-mediated selection in L. pubescens, differential behavior of the pollinators in morning and evening did not seem to explain flower color polymorphism.}, } @article {pmid29375781, year = {2018}, author = {Schull, Q and Robin, JP and Dobson, FS and Saadaoui, H and Viblanc, VA and Bize, P}, title = {Experimental stress during molt suggests the evolution of condition-dependent and condition-independent ornaments in the king penguin.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1084-1095}, pmid = {29375781}, issn = {2045-7758}, abstract = {Sexual selection and social selection are two important theories proposed for explaining the evolution of colorful ornamental traits in animals. Understanding signal honesty requires studying how environmental and physiological factors during development influence the showy nature of sexual and social ornaments. We experimentally manipulated physiological stress and immunity status during the molt in adult king penguins (Aptenodytes patagonicus), and studied the consequences of our treatments on colourful ornaments (yellow-orange and UV beak spots and yellow-orange auricular feather patches) known to be used in sexual and social contexts in this species. Whereas some ornamental features showed strong condition-dependence (yellow auricular feather chroma, yellow and UV chroma of the beak), others were condition-independent and remained highly correlated before and after the molt (auricular patch size and beak UV hue). Our study provides a rare examination of the links between ornament determinism and selection processes in the wild. We highlight the coexistence of ornaments costly to produce that may be honest signals used in mate choice, and ornaments for which honesty may be enforced by social mediation or rely on genetic constraints.}, } @article {pmid29375780, year = {2018}, author = {Lough-Stevens, M and Schultz, NG and Dean, MD}, title = {The baubellum is more developmentally and evolutionarily labile than the baculum.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1073-1083}, pmid = {29375780}, issn = {2045-7758}, support = {R01 GM098536/GM/NIGMS NIH HHS/United States ; }, abstract = {Understanding the evolutionary forces that influence sexual dimorphism is a fundamental goal in biology. Here, we focus on one particularly extreme example of sexual dimorphism. Many mammal species possess a bone in their penis called a baculum. The female equivalent of this bone is called the baubellum and occurs in the clitoris, which is developmentally homologous to the male penis. To understand the potential linkage between these two structures, we scored baculum/baubellum presence/absence across 163 species and analyzed their distribution in a phylogenetic framework. The majority of species (N = 134) shared the same state in males and females (both baculum and baubellum present or absent). However, the baubellum has experienced significantly more transitions, and more recent transitions, so that the remaining 29 species have a baculum but not a well-developed baubellum. Even in species where both bones are present, the baubellum shows more ontogenetic variability and harbors more morphological variation than the baculum. Our study demonstrates that the baculum and baubellum are generally correlated across mammals, but that the baubellum is more evolutionarily and developmentally labile than the baculum. The accumulation of more evolutionary transitions, especially losses in the baubellum, as well as noisier developmental patterns, suggests that the baubellum may be nonfunctional, and lost over time.}, } @article {pmid29375779, year = {2018}, author = {Weiss, M and Weigand, H and Weigand, AM and Leese, F}, title = {Genome-wide single-nucleotide polymorphism data reveal cryptic species within cryptic freshwater snail species-The case of the Ancylus fluviatilis species complex.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1063-1072}, pmid = {29375779}, issn = {2045-7758}, abstract = {DNA barcoding utilizes short standardized DNA sequences to identify species and is increasingly used in biodiversity assessments. The technique has unveiled an unforeseeably high number of morphologically cryptic species. However, if speciation has occurred relatively recently and rapidly, the use of single gene markers, and especially the exclusive use of mitochondrial markers, will presumably fail in delimitating species. Therefore, the true number of biological species might be even higher. One mechanism that can result in rapid speciation is hybridization of different species in combination with polyploidization, that is, allopolyploid speciation. In this study, we analyzed the population genetic structure of the polyploid freshwater snail Ancylus fluviatilis, for which allopolyploidization was postulated as a speciation mechanism. DNA barcoding has already revealed four cryptic species within A. fluviatilis (i.e., A. fluviatilis s. str., Ancylus sp. A-C), but early allozyme data even hint at the presence of additional cryptic lineages in Central Europe. We combined COI sequencing with high-resolution genome-wide SNP data (ddRAD data) to analyze the genetic structure of A. fluviatilis populations in a Central German low mountain range (Sauerland). The ddRAD data results indicate the presence of three cryptic species within A. fluviatilis s. str. occurring in sympatry and even syntopy, whereas mitochondrial sequence data only support the existence of one species, with shared haplotypes between species. Our study hence points to the limitations of DNA barcoding when dealing with organismal groups where speciation is assumed to have occurred rapidly, for example, through the process of allopolyploidization. We therefore emphasize that single marker DNA barcoding can underestimate the true species diversity and argue in strong favor of using genome-wide data for species delimitation in such groups.}, } @article {pmid29375778, year = {2018}, author = {Oberprieler, C and Zimmer, C and Bog, M}, title = {Are there morphological and life-history traits under climate-dependent differential selection in S Tunesian Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) populations?.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1047-1062}, pmid = {29375778}, issn = {2045-7758}, abstract = {Adaptation of morphological, physiological, or life-history traits of a plant species to heterogeneous habitats through the process of natural selection is a paramount process in evolutionary biology. We have used a population genomic approach to disentangle selection-based and demography-based variation in morphological and life-history traits in the crucifer Diplotaxis harra (Forssk.) Boiss. (Brassicaceae) encountered in populations along aridity gradients in S Tunisia. We have genotyped 182 individuals from 12 populations of the species ranging from coastal to semidesert habitats using amplified fragment length polymorphism (AFLP) fingerprinting and assessed a range of morphological and life-history traits from their progeny cultivated under common-garden conditions. Application of three different statistical approaches for searching AFLP loci under selection allowed us to characterize candidate loci, for which their association with the traits assessed was tested for statistical significance and correlation with climate data. As a key result of this study, we find that only the shape of cauline leaves seems to be under differential selection along the aridity gradient in S Tunisian populations of Diplotaxis harra, while for all other traits studied neutral biogeographical and/or random factors could not be excluded as explanation for the variation observed. The counter-intuitive finding that plants from populations with more arid habitats produce broader leaves under optimal conditions of cultivation than those from more mesic habitats is interpreted as being ascribable to selection for a higher plasticity in this trait under more unpredictable semidesert conditions compared to the more predictable ones in coastal habitats.}, } @article {pmid29375777, year = {2018}, author = {Sitters, J and Olde Venterink, H}, title = {A stoichiometric perspective of the effect of herbivore dung on ecosystem functioning.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1043-1046}, pmid = {29375777}, issn = {2045-7758}, abstract = {Ungulate herbivores play a prominent role in maintaining the tree-grass balance in African savannas. Their top-down role through selective feeding on either trees or grasses is well studied, but their bottom-up role through deposition of nutrients in dung and urine has been overlooked. Here, we propose a novel concept of savanna ecosystem functioning in which the balance between trees and grasses is maintained through stoichiometric differences in dung of herbivores that feed on them. We describe a framework in which N2-fixing trees and grasses, as well as ungulate browsing and grazing herbivores, occupy opposite positions in an interconnected cycle of processes. The framework makes the testable assumption that the differences in dung N:P ratio among browsers and grazers are large enough to influence competitive interactions between N2-fixing trees and grasses. Other key elements of our concept are supported with field data from a Kenyan savanna.}, } @article {pmid29375776, year = {2018}, author = {Iglesias-Carrasco, M and Head, ML and Martín, J and Cabido, C}, title = {Increased temperature disrupts chemical communication in some species but not others: The importance of local adaptation and distribution.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1031-1042}, pmid = {29375776}, issn = {2045-7758}, abstract = {Environmental conditions experienced by a species during its evolutionary history may shape the signals it uses for communication. Consequently, rapid environmental changes may lead to less effective signals, which interfere with communication between individuals, altering life history traits such as predator detection and mate searching. Increased temperature can reduce the efficacy of scent marks released by male lizards, but the extent to which this negative effect is related to specific biological traits and evolutionary histories across species and populations have not been explored. We experimentally tested how increased temperature affects the efficacy of chemical signals of high- and low-altitude populations of three lizard species that differ in their ecological requirements and altitudinal distributions. We tested the behavioral chemosensory responses of males from each species and population to male scent marks that had been incubated at one of two temperatures (cold 16°C or hot 20°C). In high-altitude populations of a mountain species (Iberolacerta monticola), the efficacy of chemical signals (i.e., latency time and number of tongue flicks) was lower after scent marks had been exposed to a hot temperature. The temperature that scent marks were incubated at did not affect the efficacy of chemical signals in a ubiquitous species (Podarcis muralis) or another mountain species (I. bonalli). Our results suggest that specific ecological traits arising through local adaptation to restricted distributions may be important in determining species vulnerability to climatic change.}, } @article {pmid29375775, year = {2018}, author = {Vowles, T and Lindwall, F and Ekblad, A and Bahram, M and Furneaux, BR and Ryberg, M and Björk, RG}, title = {Complex effects of mammalian grazing on extramatrical mycelial biomass in the Scandes forest-tundra ecotone.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1019-1030}, pmid = {29375775}, issn = {2045-7758}, abstract = {Mycorrhizal associations are widespread in high-latitude ecosystems and are potentially of great importance for global carbon dynamics. Although large herbivores play a key part in shaping subarctic plant communities, their impact on mycorrhizal dynamics is largely unknown. We measured extramatrical mycelial (EMM) biomass during one growing season in 16-year-old herbivore exclosures and unenclosed control plots (ambient), at three mountain birch forests and two shrub heath sites, in the Scandes forest-tundra ecotone. We also used high-throughput amplicon sequencing for taxonomic identification to investigate differences in fungal species composition. At the birch forest sites, EMM biomass was significantly higher in exclosures (1.36 ± 0.43 g C/m2) than in ambient conditions (0.66 ± 0.17 g C/m2) and was positively influenced by soil thawing degree-days. At the shrub heath sites, there was no significant effect on EMM biomass (exclosures: 0.72 ± 0.09 g C/m2; ambient plots: 1.43 ± 0.94). However, EMM biomass was negatively related to Betula nana abundance, which was greater in exclosures, suggesting that grazing affected EMM biomass positively. We found no significant treatment effects on fungal diversity but the most abundant ectomycorrhizal lineage/cortinarius, showed a near-significant positive effect of herbivore exclusion (p = .08), indicating that herbivory also affects fungal community composition. These results suggest that herbivory can influence fungal biomass in highly context-dependent ways in subarctic ecosystems. Considering the importance of root-associated fungi for ecosystem carbon balance, these findings could have far-reaching implications.}, } @article {pmid29375774, year = {2018}, author = {Hrovatin, K and Kunej, T}, title = {Genetic sex determination assays in 53 mammalian species: Literature analysis and guidelines for reporting standardization.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {1009-1018}, pmid = {29375774}, issn = {2045-7758}, abstract = {Erstwhile, sex was determined by observation, which is not always feasible. Nowadays, genetic methods are prevailing due to their accuracy, simplicity, low costs, and time-efficiency. However, there is no comprehensive review enabling overview and development of the field. The studies are heterogeneous, lacking a standardized reporting strategy. Therefore, our aim was to collect genetic sexing assays for mammals and assemble them in a catalogue with unified terminology. Publications were extracted from online databases using key words such as sexing and molecular. The collected data were supplemented with species and gene IDs and the type of sex-specific sequence variant (SSSV). We developed a catalogue and graphic presentation of diagnostic tests for molecular sex determination of mammals, based on 58 papers published from 2/1991 to 10/2016. The catalogue consists of five categories: species, genes, SSSVs, methods, and references. Based on the analysis of published literature, we propose minimal requirements for reporting, consisting of: species scientific name and ID, genetic sequence with name and ID, SSSV, methodology, genomic coordinates (e.g., restriction sites, SSSVs), amplification system, and description of detected amplicon and controls. The present study summarizes vast knowledge that has up to now been scattered across databases, representing the first step toward standardization regarding molecular sexing, enabling a better overview of existing tests and facilitating planned designs of novel tests. The project is ongoing; collecting additional publications, optimizing field development, and standardizing data presentation are needed.}, } @article {pmid29375773, year = {2018}, author = {Graf, PM and Wilson, RP and Sanchez, LC and Hacklӓnder, K and Rosell, F}, title = {Diving behavior in a free-living, semi-aquatic herbivore, the Eurasian beaver Castor fiber.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {997-1008}, pmid = {29375773}, issn = {2045-7758}, abstract = {Semi-aquatic mammals have secondarily returned to the aquatic environment, although they spend a major part of their life operating in air. Moving both on land, as well as in, and under water is challenging because such species are considered to be imperfectly adapted to both environments. We deployed accelerometers combined with a depth sensor to study the diving behavior of 12 free-living Eurasian beavers Castor fiber in southeast Norway between 2009 and 2011 to examine the extent to which beavers conformed with mass-dependent dive capacities, expecting them to be poorer than wholly aquatic species. Dives were generally shallow (<1 m) and of short duration (<30 s), suggesting that the majority of dives were aerobic. Dive parameters such as maximum diving depth, dive duration, and bottom phase duration were related to the effort during different dive phases and the maximum depth reached. During the descent, mean vectorial dynamic body acceleration (VeDBA-a proxy for movement power) was highest near the surface, probably due to increased upthrust linked to fur- and lung-associated air. Inconsistently though, mean VeDBA underwater was highest during the ascent when this air would be expected to help drive the animals back to the surface. Higher movement costs during ascents may arise from transporting materials up, the air bubbling out of the fur, and/or the animals' exhaling during the bottom phase of the dive. In a manner similar to other homeotherms, beavers extended both dive and bottom phase durations with diving depth. Deeper dives tended to have a longer bottom phase, although its duration was shortened with increased VeDBA during the bottom phase. Water temperature did not affect diving behavior. Overall, the beavers' dive profile (depth, duration) was similar to other semi-aquatic freshwater divers. However, beavers dived for only 2.8% of their active time, presumably because they do not rely on diving for food acquisition.}, } @article {pmid29375772, year = {2018}, author = {Hasegawa, M and Arai, E}, title = {Sexually dimorphic swallows have higher extinction risk.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {992-996}, pmid = {29375772}, issn = {2045-7758}, abstract = {The effect of sexual selection on extinction risk remains unclear. In theory, sexual selection can lead to both increase and decrease extinction probability depending on the ecology of the study system. Thus, combining different groups might obscure patterns that can be found in groups that share similar ecological features. Using phylogenetic comparative analysis, we studied sexual plumage dimorphism in relation to the perceived risk of extinction in hirundines (subfamily: Hirundininae), in which all species are socially monogamous aerial foragers. Among the 72 species studied, five species are facing a perceived threat of extinction. Species with sexually dimorphic plumage had a higher risk of extinction than did species with sexually monomorphic plumage. Likewise, when focusing solely on tail ornamentation, species that exhibit a sexual dimorphism in tail length had a higher risk of extinction than did other species. In Hirundininae, which are affected a great deal by severe weather, sexual selection and the resultant sexual dimorphism would increase extinction risk.}, } @article {pmid29375771, year = {2018}, author = {Toman, J and Flegr, J}, title = {General environmental heterogeneity as the explanation of sexuality? Comparative study shows that ancient asexual taxa are associated with both biotically and abiotically homogeneous environments.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {973-991}, pmid = {29375771}, issn = {2045-7758}, abstract = {Ecological theories of sexual reproduction assume that sexuality is advantageous in certain conditions, for example, in biotically or abiotically more heterogeneous environments. Such theories thus could be tested by comparative studies. However, the published results of these studies are rather unconvincing. Here, we present the results of a new comparative study based exclusively on the ancient asexual clades. The association with biotically or abiotically homogeneous environments in these asexual clades was compared with the same association in their sister, or closely related, sexual clades. Using the conservative definition of ancient asexuals (i.e., age >1 million years), we found eight pairs of taxa of sexual and asexual species, six differing in the heterogeneity of their inhabited environment on the basis of available data. The difference between the environmental type associated with the sexual and asexual species was then compared in an exact binomial test. The results showed that the majority of ancient asexual clades tend to be associated with biotically, abiotically, or both biotically and abiotically more homogeneous environments than their sexual controls. In the exploratory part of the study, we found that the ancient asexuals often have durable resting stages, enabling life in subjectively homogeneous environments, live in the absence of intense biotic interactions, and are very often sedentary, inhabiting benthos, and soil. The consequences of these findings for the ecological theories of sexual reproduction are discussed.}, } @article {pmid29375770, year = {2018}, author = {Behney, AC and O'Shaughnessy, R and Eichholz, MW and Stafford, JD}, title = {Indirect risk effects reduce feeding efficiency of ducks during spring.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {961-972}, pmid = {29375770}, issn = {2045-7758}, abstract = {Indirect risk effects of predators on prey behavior can have more of an impact on prey populations than direct consumptive effects. Predation risk can elicit more vigilance behavior in prey, reducing the amount of time available for other activities, such as foraging, which could potentially reduce foraging efficiency. Understanding the conditions associated with predation risk and the specific effects predation risk have on prey behavior is important because it has direct influences on the profitability of food items found under various conditions and states of the forager. The goals of this study were to assess how ducks perceived predation risk in various habitat types and how strongly perceived risk versus energetic demand affected foraging behavior. We manipulated food abundance in different wetland types in Illinois, USA to reduce confounding between food abundance and vegetation structure. We conducted focal-animal behavioral samples on five duck species in treatment and control plots and used generalized linear mixed-effects models to compare the effects of vegetation structure versus other factors on the intensity with which ducks fed and the duration of feeding stints. Mallards fed more intensively and, along with blue-winged teal, used longer feeding stints in open habitats, consistent with the hypothesis that limited visibility was perceived to have a greater predation risk than unlimited visibility. The species temporally nearest to nesting, wood ducks, were willing to take more risks for a greater food reward, consistent with an increase in a marginal value of energy as they approached nesting. Our results indicate that some duck species value energy differently based on the surrounding vegetation structure and density. Furthermore, increases in the marginal value of energy can be more influential than perceived risk in shaping foraging behavior patterns. Based on these findings, we conclude that the value of various food items is not solely determined by energy contained in the item but by conditions in which it is found and the state of the forager.}, } @article {pmid29375769, year = {2018}, author = {McCulloch, GA and Waters, JM}, title = {Does wing reduction influence the relationship between altitude and insect body size? A case study using New Zealand's diverse stonefly fauna.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {953-960}, pmid = {29375769}, issn = {2045-7758}, abstract = {Researchers have long been intrigued by evolutionary processes that explain biological diversity. Numerous studies have reported strong associations between animal body size and altitude, but insect analyses have often yielded equivocal results. Here, we analyze a collection database of New Zealand's diverse endemic stonefly fauna (106 species across 21 genera) to test for relationships between altitude and plecopteran body size. This insect assemblage includes a variety of wing-reduced (26 spp) and fully winged (80 spp) taxa and covers a broad range of altitudes (0-2,000 m). We detected significant relationships between altitude and body size for wing-reduced, but not fully winged, stonefly taxa. These results suggest that, while the maintenance of flight apparatus might place a constraint on body size in some fully winged species, the loss of flight may free insects from this evolutionary constraint. We suggest that rapid switches in insect dispersal ability may facilitate rapid evolutionary shifts across a number of biological attributes and may explain the inconsistent results from previous macroecological analyses of insect assemblages.}, } @article {pmid29375768, year = {2018}, author = {Planillo, A and Malo, JE}, title = {Infrastructure features outperform environmental variables explaining rabbit abundance around motorways.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {942-952}, pmid = {29375768}, issn = {2045-7758}, abstract = {Human disturbance is widespread across landscapes in the form of roads that alter wildlife populations. Knowing which road features are responsible for the species response and their relevance in comparison with environmental variables will provide useful information for effective conservation measures. We sampled relative abundance of European rabbits, a very widespread species, in motorway verges at regional scale, in an area with large variability in environmental and infrastructure conditions. Environmental variables included vegetation structure, plant productivity, distance to water sources, and altitude. Infrastructure characteristics were the type of vegetation in verges, verge width, traffic volume, and the presence of embankments. We performed a variance partitioning analysis to determine the relative importance of two sets of variables on rabbit abundance. Additionally, we identified the most important variables and their effects model averaging after model selection by AICc on hypothesis-based models. As a group, infrastructure features explained four times more variability in rabbit abundance than environmental variables, being the effects of the former critical in motorway stretches located in altered landscapes with no available habitat for rabbits, such as agricultural fields. Model selection and Akaike weights showed that verge width and traffic volume are the most important variables explaining rabbit abundance index, with positive and negative effects, respectively. In the light of these results, the response of species to the infrastructure can be modulated through the modification of motorway features, being some of them manageable in the design phase. The identification of such features leads to suggestions for improvement through low-cost corrective measures and conservation plans. As a general indication, keeping motorway verges less than 10 m wide will prevent high densities of rabbits and avoid the unwanted effects that rabbit populations can generate in some areas.}, } @article {pmid29375767, year = {2018}, author = {Lintott, PR and Davison, S and van Breda, J and Kubasiewicz, L and Dowse, D and Daisley, J and Haddy, E and Mathews, F}, title = {Ecobat: An online resource to facilitate transparent, evidence-based interpretation of bat activity data.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {935-941}, pmid = {29375767}, issn = {2045-7758}, abstract = {Acoustic surveys of bats are one of the techniques most commonly used by ecological practitioners. The results are used in Ecological Impact Assessments to assess the likely impacts of future developments on species that are widely protected in law, and to monitor developments' postconstruction. However, there is no standardized methodology for analyzing or interpreting these data, which can make the assessment of the ecological value of a site very subjective. Comparisons of sites and projects are therefore difficult for ecologists and decision-makers, for example, when trying to identify the best location for a new road based on relative bat activity levels along alternative routes. Here, we present a new web-based, data-driven tool, Ecobat, which addresses the need for a more robust way of interpreting ecological data. Ecobat offers users an easy, standardized, and objective method for analyzing bat activity data. It allows ecological practitioners to compare bat activity data at regional and national scales and to generate a numerical indicator of the relative importance of a night's worth of bat activity. The tool is free and open-source; because the underlying algorithms are already developed, it could easily be expanded to new geographical regions and species. Data donation is required to ensure the robustness of the analyses; we use a positive feedback mechanism to encourage ecological practitioners to share data by providing in return high quality, contextualized data analysis, and graphical visualizations for direct use in ecological reports.}, } @article {pmid29375766, year = {2018}, author = {Meik, JM and Makowsky, R}, title = {Minimum area thresholds for rattlesnakes and colubrid snakes on islands in the Gulf of California, Mexico.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {928-934}, pmid = {29375766}, issn = {2045-7758}, support = {T32 HL072757/HL/NHLBI NIH HHS/United States ; }, abstract = {We expand a framework for estimating minimum area thresholds to elaborate biogeographic patterns between two groups of snakes (rattlesnakes and colubrid snakes) on islands in the western Gulf of California, Mexico. The minimum area thresholds for supporting single species versus coexistence of two or more species relate to hypotheses of the relative importance of energetic efficiency and competitive interactions within groups, respectively. We used ordinal logistic regression probability functions to estimate minimum area thresholds after evaluating the influence of island area, isolation, and age on rattlesnake and colubrid occupancy patterns across 83 islands. Minimum area thresholds for islands supporting one species were nearly identical for rattlesnakes and colubrids (~1.7 km2), suggesting that selective tradeoffs for distinctive life history traits between rattlesnakes and colubrids did not result in any clear advantage of one life history strategy over the other on islands. However, the minimum area threshold for supporting two or more species of rattlesnakes (37.1 km2) was over five times greater than it was for supporting two or more species of colubrids (6.7 km2). The great differences between rattlesnakes and colubrids in minimum area required to support more than one species imply that for islands in the Gulf of California relative extinction risks are higher for coexistence of multiple species of rattlesnakes and that competition within and between species of rattlesnakes is likely much more intense than it is within and between species of colubrids.}, } @article {pmid29375765, year = {2018}, author = {Zhang, Z and Shan, L and Li, Y}, title = {Prolonged dry periods between rainfall events shorten the growth period of the resurrection plant Reaumuria soongorica.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {920-927}, pmid = {29375765}, issn = {2045-7758}, abstract = {The resurrection plant Reaumuria soongorica is widespread across Asia, southern Europe, and North Africa and is considered to be a constructive keystone species in desert ecosystems, but the impacts of climate change on this species in desert ecosystems are unclear. Here, the morphological responses of R. soongorica to changes in rainfall quantity (30% reduction and 30% increase in rainfall quantity) and interval (50% longer drought interval between rainfall events) were tested. Stage-specific changes in growth were monitored by sampling at the beginning, middle, and end of the growing season. Reduced rainfall decreased the aboveground and total biomass, while additional precipitation generally advanced R. soongorica growth and biomass accumulation. An increased interval between rainfall events resulted in an increase in root biomass in the middle of the growing season, followed by a decrease toward the end. The response to the combination of increased rainfall quantity and interval was similar to the response to increased interval alone, suggesting that the effects of changes in rainfall patterns exert a greater influence than increased rainfall quantity. Thus, despite the short duration of this experiment, consequences of changes in rainfall regime on seedling growth were observed. In particular, a prolonged rainfall interval shortened the growth period, suggesting that climate change-induced rainfall variability may have significant effects on the structure and functioning of desert ecosystems.}, } @article {pmid29375764, year = {2018}, author = {Kilroy, C and Novis, P}, title = {Is Didymosphenia geminata an introduced species in New Zealand? Evidence from trends in water chemistry, and chloroplast DNA.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {904-919}, pmid = {29375764}, issn = {2045-7758}, abstract = {Defining the geographic origins of free-living aquatic microorganisms can be problematic because many such organisms have ubiquitous distributions, and proving absence from a region is practically impossible. Geographic origins become important if microorganisms have invasive characteristics. The freshwater diatom Didymosphenia geminata is a potentially ubiquitous microorganism for which the recent global expansion of nuisance proliferations has been attributed to environmental change. The changes may include declines in dissolved reactive phosphorus (DRP) to low levels (e.g., <2 mg/m3) and increases in dissolved inorganic nitrogen (DIN) to >10 mg/m3 because both these nutrient conditions are associated with nuisance proliferations of D. geminata. Proliferations of D. geminata have been observed in South Island, New Zealand, since 2004. We aimed to address the ubiquity hypothesis for D. geminata in New Zealand using historical river water nutrient data and new molecular analyses. We used 15 years of data at 77 river sites to assess whether trends in DRP or DIN prior to the spread of D. geminata were consistent with a transition from a rare, undetected, species to a nuisance species. We used new sequences of chloroplast regions to examine the genetic similarity of D. geminata populations from New Zealand and six overseas locations. We found no evidence for declines in DRP concentrations since 1989 that could explain the spread of proliferations since 2004. At some affected sites, lowest DRP occurred before 2004. Trends in DIN also did not indicate enhanced suitability for D. geminata. Lack of diversity in the chloroplast intergenic regions of New Zealand populations and populations from western North America is consistent with recent dispersal to New Zealand. Our analyses did not support the proposal that D. geminata was historically present in New Zealand rivers. These results provide further evidence countering proposals of general ubiquity in freshwater diatoms and indicate that, as assumed in 2004, D. geminata is a recent arrival in New Zealand.}, } @article {pmid29375763, year = {2018}, author = {Rivest, S and Vellend, M}, title = {Herbivory and pollen limitation at the upper elevational range limit of two forest understory plants of eastern North America.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {892-903}, pmid = {29375763}, issn = {2045-7758}, abstract = {Studies of species' range limits focus most often on abiotic factors, although the strength of biotic interactions might also vary along environmental gradients and have strong demographic effects. For example, pollinator abundance might decrease at range limits due to harsh environmental conditions, and reduced plant density can reduce attractiveness to pollinators and increase or decrease herbivory. We tested for variation in the strength of pollen limitation and herbivory by ungulates along a gradient leading to the upper elevational range limits of Trillium erectum (Melanthiaceae) and Erythronium americanum (Liliaceae) in Mont Mégantic National Park, Québec, Canada. In T. erectum, pollen limitation was higher at the range limit, but seed set decreased only slightly with elevation and only in one of two years. In contrast, herbivory of T. erectum increased from <10% at low elevations to >60% at the upper elevational range limit. In E. americanum, we found no evidence of pollen limitation despite a significant decrease in seed set with elevation, and herbivory was low across the entire gradient. Overall, our results demonstrate the potential for relatively strong negative interactions (herbivory) and weak positive interactions (pollination) at plant range edges, although this was clearly species specific. To the extent that these interactions have important demographic consequences-highly likely for herbivory on Trillium, based on previous studies-such interactions might play a role in determining plant species' range limits along putatively climatic gradients.}, } @article {pmid29375762, year = {2018}, author = {Tang, Z and Sun, X and Luo, Z and He, N and Sun, OJ}, title = {Effects of temperature, soil substrate, and microbial community on carbon mineralization across three climatically contrasting forest sites.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {879-891}, pmid = {29375762}, issn = {2045-7758}, abstract = {How biotic and abiotic factors influence soil carbon (C) mineralization rate (RS) has recently emerged as one of the focal interests in ecological studies. To determine the relative effects of temperature, soil substrate and microbial community on Rs, we conducted a laboratory experiment involving reciprocal microbial inoculations of three zonal forest soils, and measured RS over a 61-day period at three temperatures (5, 15, and 25°C). Results show that both Rs and the cumulative emission of C (Rcum), normalized to per unit soil organic C (SOC), were significantly affected by incubation temperature, soil substrate, microbial inoculum treatment, and their interactions (p < .05). Overall, the incubation temperature had the strongest effect on the RS; at given temperatures, soil substrate, microbial inoculum treatment, and their interaction all significantly affected both Rs (p < .001) and Rcum (p ≤ .01), but the effect of soil substrate was much stronger than others. There was no consistent pattern of thermal adaptation in microbial decomposition of SOC in the reciprocal inoculations. Moreover, when different sources of microbial inocula were introduced to the same soil substrate, the microbial community structure converged with incubation without altering the overall soil enzyme activities; when different types of soil substrate were inoculated with the same sources of microbial inocula, both the microbial community structure and soil enzyme activities diverged. Overall, temperature plays a predominant role in affecting Rs and Rcum, while soil substrate determines the mineralizable SOC under given conditions. The role of microbial community in driving SOC mineralization is weaker than that of climate and soil substrate, because soil microbial community is both affected, and adapts to, climatic factors and soil matrix.}, } @article {pmid29375761, year = {2018}, author = {Christensen-Dalsgaard, S and May, R and Lorentsen, SH}, title = {Taking a trip to the shelf: Behavioral decisions are mediated by the proximity to foraging habitats in the black-legged kittiwake.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {866-878}, pmid = {29375761}, issn = {2045-7758}, abstract = {For marine top predators like seabirds, the oceans represent a multitude of habitats regarding oceanographic conditions and food availability. Worldwide, these marine habitats are being altered by changes in climate and increased anthropogenic impact. This is causing a growing concern on how seabird populations might adapt to these changes. Understanding how seabird populations respond to fluctuating environmental conditions and to what extent behavioral flexibility can buffer variations in food availability can help predict how seabirds may cope with changes in the marine environment. Such knowledge is important to implement proper long-term conservation measures intended to protect marine predators. We explored behavioral flexibility in choice of foraging habitat of chick-rearing black-legged kittiwakes Rissa tridactyla during multiple years. By comparing foraging behavior of individuals from two colonies with large differences in oceanographic conditions and distances to predictable feeding areas at the Norwegian shelf break, we investigated how foraging decisions are related to intrinsic and extrinsic factors. We found that proximity to the shelf break determined which factors drove the decision to forage there. At the colony near the shelf break, time of departure from the colony and wind speed were most important in driving the choice of habitat. At the colony farther from the shelf break, the decision to forage there was driven by adult body condition. Birds furthermore adjusted foraging behavior metrics according to time of the day, weather conditions, body condition, and the age of the chicks. The study shows that kittiwakes have high degree of flexibility in their behavioral response to a variable marine environment, which might help them buffer changes in prey distribution around the colonies. The flexibility is, however, dependent on the availability of foraging habitats near the colony.}, } @article {pmid29375760, year = {2018}, author = {Park, JS and Post, DM}, title = {Evolutionary history of Daphnia drives divergence in grazing selectivity and alters temporal community dynamics of producers.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {859-865}, pmid = {29375760}, issn = {2045-7758}, abstract = {Consumers with different seasonal life histories encounter different communities of producers during specific seasonal phases. If consumers evolve to prefer the producers that they encounter, then consumers may reciprocally influence the temporal composition of producer communities. Here, we study the keystone consumer Daphnia ambigua, whose seasonal life history has diverged due to intraspecific predator divergence across lakes of New England. We ask whether grazing preferences of Daphnia have diverged also and test whether any grazing differences influence temporal composition patterns of producers. We reared clonal populations of Daphnia from natural populations representing the two diverged life history types for multiple generations. We conducted short-term (24 hr) and long-term (27 days) grazing experiments in equal polycultures consisting of three diatom and two green algae species, treated with no consumer, Daphnia from lakes with anadromous alewife, or from lakes with landlocked alewife. After 24 hr, life history and grazing preference divergence in Daphnia ambigua drove significant differences in producer composition. However, those differences disappeared at the end of the 27-day experiment. Our results illustrate that, despite potentially more complex long-term dynamics, a multitrophic cascade of evolutionary divergence from a predator can influence temporal community dynamics at the producer level.}, } @article {pmid29375759, year = {2018}, author = {Albuquerque, F and Beier, P}, title = {Improving the use of environmental diversity as a surrogate for species representation.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {852-858}, pmid = {29375759}, issn = {2045-7758}, abstract = {The continuous p-median approach to environmental diversity (ED) is a reliable way to identify sites that efficiently represent species. A recently developed maximum dispersion (maxdisp) approach to ED is computationally simpler, does not require the user to reduce environmental space to two dimensions, and performed better than continuous p-median for datasets of South African animals. We tested whether maxdisp performs as well as continuous p-median for 12 datasets that included plants and other continents, and whether particular types of environmental variables produced consistently better models of ED. We selected 12 species inventories and atlases to span a broad range of taxa (plants, birds, mammals, reptiles, and amphibians), spatial extents, and resolutions. For each dataset, we used continuous p-median ED and maxdisp ED in combination with five sets of environmental variables (five combinations of temperature, precipitation, insolation, NDVI, and topographic variables) to select environmentally diverse sites. We used the species accumulation index (SAI) to evaluate the efficiency of ED in representing species for each approach and set of environmental variables. Maxdisp ED represented species better than continuous p-median ED in five of 12 biodiversity datasets, and about the same for the other seven biodiversity datasets. Efficiency of ED also varied with type of variables used to define environmental space, but no particular combination of variables consistently performed best. We conclude that maxdisp ED performs at least as well as continuous p-median ED, and has the advantage of faster and simpler computation. Surprisingly, using all 38 environmental variables was not consistently better than using subsets of variables, nor did any subset emerge as consistently best or worst; further work is needed to identify the best variables to define environmental space. Results can help ecologists and conservationists select sites for species representation and assist in conservation planning.}, } @article {pmid29375758, year = {2018}, author = {Sánchez-Mercado, A and Rodríguez-Clark, KM and Miranda, J and Ferrer-Paris, JR and Coyle, B and Toro, S and Cardozo-Urdaneta, A and Braun, MJ}, title = {How to deal with ground truthing affected by human-induced habitat change?: Identifying high-quality habitats for the Critically Endangered Red Siskin.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {841-851}, pmid = {29375758}, issn = {2045-7758}, abstract = {Species distribution models (SDM) can be valuable for identifying key habitats for conservation management of threatened taxa, but anthropogenic habitat change can undermine SDM accuracy. We used data for the Red Siskin (Spinus cucullatus), a critically endangered bird and ground truthing to examine anthropogenic habitat change as a source of SDM inaccuracy. We aimed to estimate: (1) the Red Siskin's historic distribution in Venezuela; (2) the portion of this historic distribution lost to vegetation degradation; and (3) the location of key habitats or areas with both, a high probability of historic occurrence and a low probability of vegetation degradation. We ground-truthed 191 locations and used expert opinion as well as landscape characteristics to classify species' habitat suitability as excellent, good, acceptable, or poor. We fit a Random Forest model (RF) and Enhanced Vegetation Index (EVI) time series to evaluate the accuracy and precision of the expert categorization of habitat suitability. We estimated the probability of historic occurrence by fitting a MaxLike model using 88 presence records (1960-2013) and data on forest cover and aridity index. Of the entire study area, 23% (20,696 km2) had a historic probability of Red Siskin occurrence over 0.743. Furthermore, 85% of ground-truthed locations had substantial reductions in mean EVI, resulting in key habitats totaling just 976 km2, in small blocks in the western and central regions. Decline in Area of Occupancy over 15 years was between 40% and 95%, corresponding to an extinction risk category between Vulnerable and Critically Endangered. Relating key habitats with other landscape features revealed significant risks and opportunities for proposed conservation interventions, including the fact that ongoing vegetation degradation could limit the establishment of reintroduced populations in eastern areas, while the conservation of remaining key habitats on private lands could be improved with biodiversity-friendly agri- and silviculture programs.}, } @article {pmid29375757, year = {2018}, author = {Miller, MA and Kinsella, JM and Snow, RW and Hayes, MM and Falk, BG and Reed, RN and Mazzotti, FJ and Guyer, C and Romagosa, CM}, title = {Parasite spillover: indirect effects of invasive Burmese pythons.}, journal = {Ecology and evolution}, volume = {8}, number = {2}, pages = {830-840}, pmid = {29375757}, issn = {2045-7758}, abstract = {Identification of the origin of parasites of nonindigenous species (NIS) can be complex. NIS may introduce parasites from their native range and acquire parasites from within their invaded range. Determination of whether parasites are non-native or native can be complicated when parasite genera occur within both the NIS' native range and its introduced range. We explored potential for spillover and spillback of lung parasites infecting Burmese pythons (Python bivittatus) in their invasive range (Florida). We collected 498 indigenous snakes of 26 species and 805 Burmese pythons during 2004-2016 and examined them for lung parasites. We used morphology to identify three genera of pentastome parasites, Raillietiella, a cosmopolitan form, and Porocephalus and Kiricephalus, both New World forms. We sequenced these parasites at one mitochondrial and one nuclear locus and showed that each genus is represented by a single species, R. orientalis, P. crotali, and K. coarctatus. Pythons are host to R. orientalis and P. crotali, but not K. coarctatus; native snakes are host to all three species. Sequence data show that pythons introduced R. orientalis to North America, where this parasite now infects native snakes. Additionally, our data suggest that pythons are competent hosts to P. crotali, a widespread parasite native to North and South America that was previously hypothesized to infect only viperid snakes. Our results indicate invasive Burmese pythons have affected parasite-host dynamics of native snakes in ways that are consistent with parasite spillover and demonstrate the potential for indirect effects during invasions. Additionally, we show that pythons have acquired a parasite native to their introduced range, which is the initial condition necessary for parasite spillback.}, } @article {pmid29374497, year = {2018}, author = {Lewis, CC and Puspitasari, A and Boyd, MR and Scott, K and Marriott, BR and Hoffman, M and Navarro, E and Kassab, H}, title = {Implementing measurement based care in community mental health: a description of tailored and standardized methods.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {76}, pmid = {29374497}, issn = {1756-0500}, support = {R01 MH103310/MH/NIMH NIH HHS/United States ; R01MH103310//National Institute of Mental Health/ ; }, mesh = {Community Mental Health Services/*methods ; Depression/therapy ; Electronic Health Records ; Health Plan Implementation/*methods ; Health Services Research/*methods ; Humans ; Randomized Controlled Trials as Topic/methods ; *Research Design ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: Although tailored implementation methods are touted as superior to standardized, few researchers have directly compared the two and little guidance regarding the specific details of each method exist. Our study compares these methods in a dynamic cluster randomized trial seeking to optimize implementation of measurement based care (MBC) for depression in community behavioral health. This specific manuscript provides a detailed, replicable account of the components of each multi-faceted implementation method.

RESULTS: The standardized best practice method includes training, consultation, a clinical guideline, and electronic health record enhancements with the goal to optimize the delivery of MBC with fidelity. Conversely, the tailored, customized and collaborative method is informed by recent implementation science advancements and begins with a needs assessment, followed by tailored training that feeds back barriers data to clinicians, the formation of an implementation team, a clinician-driven clinic-specific guideline, and the use of fidelity data to inform implementation team activities; the goal of the tailored condition is to ensure the intervention and implementation strategies address unique factors of the context. The description of these methods will inform others seeking to implement MBC, as well as those planning to use standardized or tailored implementation methods for interventions beyond behavioral health.}, } @article {pmid29374496, year = {2018}, author = {Reveillaud, J and Anderson, R and Reves-Sohn, S and Cavanaugh, C and Huber, JA}, title = {Metagenomic investigation of vestimentiferan tubeworm endosymbionts from Mid-Cayman Rise reveals new insights into metabolism and diversity.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {19}, pmid = {29374496}, issn = {2049-2618}, support = {grant NNX-32709AB75G/NASA/NASA/United States ; C-DEBI//National Science Foundation/International ; }, mesh = {Animals ; Autotrophic Processes ; Bacteria/*classification/genetics/isolation & purification ; Genes, Bacterial ; Hydrothermal Vents ; Metagenomics/*methods ; Phylogeny ; Polychaeta/*microbiology ; RNA, Ribosomal, 16S/*genetics ; Symbiosis ; }, abstract = {BACKGROUND: The microbial endosymbionts of two species of vestimentiferan tubeworms (Escarpia sp. and Lamellibrachia sp.2) collected from an area of low-temperature hydrothermal diffuse vent flow at the Mid-Cayman Rise (MCR) in the Caribbean Sea were characterized using microscopy, phylogenetic analyses, and a metagenomic approach.

RESULTS: Bacteria, with a typical Gram negative cell envelope contained within membrane-bound vacuoles, were observed within the trophosome of both tubeworm species. Phylogenetic analysis of the 16S rRNA gene and ITS region suggested MCR individuals harbored highly similar endosymbionts that were > 98% identical, with the exception of two symbionts that showed a 60 bp insertion within the ITS region. All sequences from MCR endosymbionts formed a separate well-supported clade that diverged from those of symbionts of seep and vent vestimentiferans from the Pacific, Gulf of Mexico, and Mediterranean Sea. The metagenomes of the symbionts of two specimens of each tubeworm species were sequenced, and two distinct Gammaproteobacteria metagenome-assembled genomes (MAGs) of more than 4 Mbp assembled. An Average Nucleotide Identity (ANI) of 86.5% between these MAGs, together with distinct 16S rRNA gene and ITS sequences, indicate the presence of multiple endosymbiont phylotypes at the MCR, with one MAG shared between one Escarpia and two Lamellibrachia individuals, indicating these endosymbionts are not specific to either host species. Genes for sulfur and hydrogen oxidation, nitrate reduction (assimilatory and dissimilatory), glycolysis and the Krebs cycle, peptide, sugar, and lipid transporters, and both rTCA and CBB carbon fixation cycles were detected in the MAGs, highlighting key and shared functions with symbiont metagenomes of the vestimentiferans Riftia, Tevnia, and Ridgeia from the Pacific. The potential for a second hydrogen oxidation pathway (via a bidirectional hydrogenase), formate dehydrogenase, a catalase, and several additional peptide transporters were found exclusively in the MCR endosymbiont MAGs.

CONCLUSIONS: The present study adds new evidence that tubeworm endosymbionts can potentially switch from autotrophic to heterotrophic metabolism, or may be mixotrophic, presumably while free-living, and also suggests their versatile metabolic potential may enable both the host and symbionts to exploit a wide range of environmental conditions. Together, the marked gene content and sequence dissimilarity at the rRNA operon and whole genome level between vent and seep symbionts suggest these newly described endosymbionts from the MCR belong to a novel tubeworm endosymbiont genera, introduced as Candidatus Vondammii.}, } @article {pmid29374494, year = {2018}, author = {Clarke, M and McAneney, H and Chan, F and Maguire, L}, title = {Inconsistencies in the drawing and interpretation of smiley faces: an observational study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {77}, pmid = {29374494}, issn = {1756-0500}, support = {G0901530//Medical Research Council/United Kingdom ; G0902112//Medical Research Council/United Kingdom ; }, mesh = {Adult ; Age Factors ; *Face ; *Facial Expression ; Female ; Humans ; Male ; Pattern Recognition, Visual/*physiology ; *Self Concept ; Sex Factors ; }, abstract = {OBJECTIVES: Pre-prepared smiley face symbols are used widely to gather information on, for example, satisfaction with services or health and well-being. We investigated how women and men of different ages respond when asked to draw a smiley face for themselves. Our objectives were to investigate how they differ by generating a unique set of data to explore this simple human behaviour and to illustrate the importance of considering gender and age mix in any study.

RESULTS: We collected 723 drawings, in a variety of settings. Gender and age were provided for 676 drawings (women: 511; men: 165; ≤ 30 years: 335; > 30 years: 341). Although similar proportions of women and men drew some features, such as closed mouths; women and those aged ≤ 30 were less likely to draw noses and outlines around the faces, and more likely to draw a classic smiley face. Our analyses provide a novel way to highlight that whenever self-reported outcomes are compared between groups, the group composition for characteristics such as gender and age may need to be considered carefully to explore whether differences in outcomes might simply arise from imbalances in those characteristics.}, } @article {pmid29374492, year = {2018}, author = {Olesen, AE and Grønlund, D and Gram, M and Skorpen, F and Drewes, AM and Klepstad, P}, title = {Prediction of opioid dose in cancer pain patients using genetic profiling: not yet an option with support vector machine learning.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {78}, pmid = {29374492}, issn = {1756-0500}, mesh = {Aged ; Analgesics, Opioid/administration & dosage/*therapeutic use ; Cancer Pain/*drug therapy/*genetics ; Catechol O-Methyltransferase/genetics ; Dose-Response Relationship, Drug ; Female ; Gene Frequency ; Genotype ; Humans ; Male ; Middle Aged ; Morphine/administration & dosage/therapeutic use ; Polymorphism, Single Nucleotide ; Receptors, Opioid, delta/genetics ; Receptors, Opioid, mu/genetics ; *Support Vector Machine ; }, abstract = {OBJECTIVE: Use of opioids for pain management has increased over the past decade; however, inadequate analgesic response is common. Genetic variability may be related to opioid efficacy, but due to the many possible combinations and variables, statistical computations may be difficult. This study investigated whether data processing with support vector machine learning could predict required opioid dose in cancer pain patients, using genetic profiling. Eighteen single nucleotide polymorphisms (SNPs) within the µ and δ opioid receptor genes and the catechol-O-methyltransferase gene were selected for analysis.

RESULTS: Data from 1237 cancer pain patients were included in the analysis. Support vector machine learning did not find any associations between the assessed SNPs and opioid dose in cancer pain patients, and hence, did not provide additional information regarding prediction of required opioid dose using genetic profiling.}, } @article {pmid29374490, year = {2018}, author = {Liu, J and Abdelfattah, A and Norelli, J and Burchard, E and Schena, L and Droby, S and Wisniewski, M}, title = {Apple endophytic microbiota of different rootstock/scion combinations suggests a genotype-specific influence.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {18}, pmid = {29374490}, issn = {2049-2618}, support = {2017YFD0201100//National Key Research and Development Program of China/International ; IS 2513-16//U.S. - Israel Binational Agricultural Research and Development Fund/International ; R2016LX01//Foundation for High-level Talents of Chongqing University of Arts and Sciences/International ; }, mesh = {Actinobacteria/classification/genetics/isolation & purification ; Ascomycota/classification/genetics/isolation & purification ; Bacteria/*classification/genetics/isolation & purification ; Basidiomycota/classification/genetics/isolation & purification ; Endophytes ; Firmicutes/classification/genetics/isolation & purification ; Fungi/*classification/genetics/isolation & purification ; Fusobacteria/classification/genetics/isolation & purification ; Genotype ; High-Throughput Nucleotide Sequencing/*methods ; Malus/*genetics/microbiology ; Microbiota ; Phylogeny ; Plant Roots/microbiology ; Proteobacteria/classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/*genetics ; }, abstract = {BACKGROUND: High-throughput amplicon sequencing spanning conserved portions of microbial genomes (16s rRNA and ITS) was used in the present study to describe the endophytic microbiota associated with three apple varieties, "Royal Gala," "Golden Delicious," and "Honey Crisp," and two rootstocks, M.9 and M.M.111. The objectives were to (1) determine if the microbiota differs in different rootstocks and apple varieties and (2) determine if specific rootstock-scion combinations influence the microbiota composition of either component.

RESULTS: Results indicated that Ascomycota (47.8%), Zygomycota (31.1%), and Basidiomycota (11.6%) were the dominant fungal phyla across all samples. The majority of bacterial sequences were assigned to Proteobacteria (58.4%), Firmicutes (23.8%), Actinobacteria (7.7%), Bacteroidetes (2%), and Fusobacteria (0.4%). Rootstocks appeared to influence the microbiota of associated grafted scion, but the effect was not statistically significant. Pedigree also had an impact on the composition of the endophytic microbiota, where closely-related cultivars had a microbial community that was more similar to each other than it was to a scion cultivar that was more distantly-related by pedigree. The more vigorous rootstock (M.M.111) was observed to possess a greater number of growth-promoting bacterial taxa, relative to the dwarfing rootstock (M.9).

CONCLUSIONS: The mechanism by which an apple genotype, either rootstock or scion, has a determinant effect on the composition of a microbial community is not known. The similarity of the microbiota in samples with a similar pedigree suggests the possibility of some level of co-evolution or selection as proposed by the "holobiont" concept in which metaorganisms have co-evolved. Clearly, however, the present information is only suggestive, and a more comprehensive analysis is needed.}, } @article {pmid29374474, year = {2018}, author = {Koile, D and Cordoba, M and de Sousa Serro, M and Kauffman, MA and Yankilevich, P}, title = {GenIO: a phenotype-genotype analysis web server for clinical genomics of rare diseases.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {25}, pmid = {29374474}, issn = {1471-2105}, mesh = {Genetic Association Studies ; Genotype ; Humans ; Internet ; Phenotype ; Rare Diseases/*genetics/pathology ; *User-Computer Interface ; }, abstract = {BACKGROUND: GenIO is a novel web-server, designed to assist clinical genomics researchers and medical doctors in the diagnostic process of rare genetic diseases. The tool identifies the most probable variants causing a rare disease, using the genomic and clinical information provided by a medical practitioner. Variants identified in a whole-genome, whole-exome or target sequencing studies are annotated, classified and filtered by clinical significance. Candidate genes associated with the patient's symptoms, suspected disease and complementary findings are identified to obtain a small manageable number of the most probable recessive and dominant candidate gene variants associated with the rare disease case. Additionally, following the American College of Medical Genetics and Genomics and the Association of Molecular Pathology (ACMG-AMP) guidelines and recommendations, all potentially pathogenic variants that might be contributing to disease and secondary findings are identified.

RESULTS: A retrospective study was performed on 40 patients with a diagnostic rate of 40%. All the known genes that were previously considered as disease causing were correctly identified in the final inherit model output lists. In previously undiagnosed cases, we had no additional yield.

CONCLUSION: This unique, intuitive and user-friendly tool to assists medical doctors in the clinical genomics diagnostic process is openly available at https://bioinformatics.ibioba-mpsp-conicet.gov.ar/GenIO/ .}, } @article {pmid29374461, year = {2018}, author = {Eriksson, JS and de Sousa, F and Bertrand, YJK and Antonelli, A and Oxelman, B and Pfeil, BE}, title = {Allele phasing is critical to revealing a shared allopolyploid origin of Medicago arborea and M. strasseri (Fabaceae).}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {9}, pmid = {29374461}, issn = {1471-2148}, support = {331024//European Research Council/International ; 2009-5206//Royal Swedish Academy of Sciences/International ; }, mesh = {*Alleles ; Base Sequence ; Evolution, Molecular ; Genes, Plant ; Hybridization, Genetic ; Medicago/*genetics ; Phylogeny ; *Polyploidy ; Population Density ; Species Specificity ; }, abstract = {BACKGROUND: Whole genome duplication plays a central role in plant evolution. There are two main classes of polyploid formation: autopolyploids which arise within one species by doubling of similar homologous genomes; in contrast, allopolyploidy (hybrid polyploidy) arise via hybridization and subsequent doubling of nonhomologous (homoeologous) genomes. The distinction between polyploid origins can be made using gene phylogenies, if alleles from each genome can be correctly retrieved. We examined whether two closely related tetraploid Mediterranean shrubs (Medicago arborea and M. strasseri) have an allopolyploid origin - a question that has remained unsolved despite substantial previous research. We sequenced and analyzed ten low-copy nuclear genes from these and related species, phasing all alleles. To test the efficacy of allele phasing on the ability to recover the evolutionary origin of polyploids, we compared these results to analyses using unphased sequences.

RESULTS: In eight of the gene trees the alleles inferred from the tetraploids formed two clades, in a non-sister relationship. Each of these clades was more closely related to alleles sampled from other species of Medicago, a pattern typical of allopolyploids. However, we also observed that alleles from one of the remaining genes formed two clades that were sister to one another, as is expected for autopolyploids. Trees inferred from unphased sequences were very different, with the tetraploids often placed in poorly supported and different positions compared to results obtained using phased alleles.

CONCLUSIONS: The complex phylogenetic history of M. arborea and M. strasseri is explained predominantly by shared allotetraploidy. We also observed that an increase in woodiness is correlated with polyploidy in this group of species and present a new possibility that woodiness could be a transgressive phenotype. Correctly phased homoeologues are likely to be critical for inferring the hybrid origin of allopolyploid species, when most genes retain more than one homoeologue. Ignoring homoeologous variation by merging the homoeologues can obscure the signal of hybrid polyploid origins and produce inaccurate results.}, } @article {pmid29374456, year = {2018}, author = {Forutan, M and Ansari Mahyari, S and Baes, C and Melzer, N and Schenkel, FS and Sargolzaei, M}, title = {Inbreeding and runs of homozygosity before and after genomic selection in North American Holstein cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {98}, pmid = {29374456}, issn = {1471-2164}, support = {051573//Dairy Research Cluster Initiative/International ; }, mesh = {Animals ; Cattle/*genetics ; Female ; Gene Frequency ; Genome ; *Homozygote ; *Inbreeding ; Male ; North America ; Pedigree ; Polymorphism, Single Nucleotide ; Population Dynamics ; *Selection, Genetic ; }, abstract = {BACKGROUND: While autozygosity as a consequence of selection is well understood, there is limited information on the ability of different methods to measure true inbreeding. In the present study, a gene dropping simulation was performed and inbreeding estimates based on runs of homozygosity (ROH), pedigree, and the genomic relationship matrix were compared to true inbreeding. Inbreeding based on ROH was estimated using SNP1101, PLINK, and BCFtools software with different threshold parameters. The effects of different selection methods on ROH patterns were also compared. Furthermore, inbreeding coefficients were estimated in a sample of genotyped North American Holstein animals born from 1990 to 2016 using 50 k chip data and ROH patterns were assessed before and after genomic selection.

RESULTS: Using ROH with a minimum window size of 20 to 50 using SNP1101 provided the closest estimates to true inbreeding in simulation study. Pedigree inbreeding tended to underestimate true inbreeding, and results for genomic inbreeding varied depending on assumptions about base allele frequencies. Using an ROH approach also made it possible to assess the effect of population structure and selection on distribution of runs of autozygosity across the genome. In the simulation, the longest individual ROH and the largest average length of ROH were observed when selection was based on best linear unbiased prediction (BLUP), whereas genomic selection showed the largest number of small ROH compared to BLUP estimated breeding values (BLUP-EBV). In North American Holsteins, the average number of ROH segments of 1 Mb or more per individual increased from 57 in 1990 to 82 in 2016. The rate of increase in the last 5 years was almost double that of previous 5 year periods. Genomic selection results in less autozygosity per generation, but more per year given the reduced generation interval.

CONCLUSIONS: This study shows that existing software based on the measurement of ROH can accurately identify autozygosity across the genome, provided appropriate threshold parameters are used. Our results show how different selection strategies affect the distribution of ROH, and how the distribution of ROH has changed in the North American dairy cattle population over the last 25 years.}, } @article {pmid29374454, year = {2018}, author = {Zuriaga, E and Romero, C and Blanca, JM and Badenes, ML}, title = {Resistance to Plum Pox Virus (PPV) in apricot (Prunus armeniaca L.) is associated with down-regulation of two MATHd genes.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {25}, pmid = {29374454}, issn = {1471-2229}, support = {RTA2013-00026-C03-01//Secretaría de Estado de Investigación, Desarrollo e Innovación/International ; }, mesh = {*Disease Resistance ; *Down-Regulation ; Genomics ; Plant Diseases/*virology ; Plant Proteins/*genetics/metabolism ; Plum Pox Virus/*physiology ; Prunus armeniaca/*genetics/metabolism/virology ; *Transcriptome ; }, abstract = {BACKGROUND: Plum pox virus (PPV), causing Sharka disease, is one of the main limiting factors for Prunus production worldwide. In apricot (Prunus armeniaca L.) the major PPV resistance locus (PPVres), comprising ~ 196 kb, has been mapped to the upper part of linkage group 1. Within the PPVres, 68 genomic variants linked in coupling to PPV resistance were identified within 23 predicted transcripts according to peach genome annotation. Taking into account the predicted functions inferred from sequence homology, some members of a cluster of meprin and TRAF-C homology domain (MATHd)-containing genes were pointed as PPV resistance candidate genes.

RESULTS: Here, we have characterized the global apricot transcriptome response to PPV-D infection identifying six PPVres locus genes (ParP-1 to ParP-6) differentially expressed in resistant/susceptible cultivars. Two of them (ParP-3 and ParP-4), that encode MATHd proteins, appear clearly down-regulated in resistant cultivars, as confirmed by qRT-PCR. Concurrently, variant calling was performed using whole-genome sequencing data of 24 apricot cultivars (10 PPV-resistant and 14 PPV-susceptible) and 2 wild relatives (PPV-susceptible). ParP-3 and ParP-4, named as Prunus armeniaca PPVres MATHd-containing genes (ParPMC), are the only 2 genes having allelic variants linked in coupling to PPV resistance. ParPMC1 has 1 nsSNP, while ParPMC2 has 15 variants, including a 5-bp deletion within the second exon that produces a frameshift mutation. ParPMC1 and ParPMC2 are adjacent and highly homologous (87.5% identity) suggesting they are paralogs originated from a tandem duplication. Cultivars carrying the ParPMC2 resistant (mutated) allele show lack of expression in both ParPMC2 and especially ParPMC1.

CONCLUSIONS: Accordingly, we hypothesize that ParPMC2 is a pseudogene that mediates down-regulation of its functional paralog ParPMC1 by silencing. As a whole, results strongly support ParPMC1 and/or ParPMC2 as host susceptibility genes required for PPV infection which silencing may confer PPV resistance trait. This finding may facilitate resistance breeding by marker-assisted selection and pave the way for gene edition approaches in Prunus.}, } @article {pmid29374255, year = {2018}, author = {}, title = {Our shared history.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {159}, doi = {10.1038/s41588-018-0049-4}, pmid = {29374255}, issn = {1546-1718}, } @article {pmid29374254, year = {2018}, author = {Barroso, I}, title = {ADCY3, neuronal primary cilia and obesity.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {166-167}, doi = {10.1038/s41588-018-0043-x}, pmid = {29374254}, issn = {1546-1718}, } @article {pmid29374253, year = {2018}, author = {Yuan, J and Gordon, A and Speyer, D and Aufrichtig, R and Zielinski, D and Pickrell, J and Erlich, Y}, title = {DNA.Land is a framework to collect genomes and phenomes in the era of abundant genetic information.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {160-165}, doi = {10.1038/s41588-017-0021-8}, pmid = {29374253}, issn = {1546-1718}, } @article {pmid29374252, year = {2018}, author = {Zaret, KS}, title = {Pioneering the chromatin landscape.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {167-169}, doi = {10.1038/s41588-017-0038-z}, pmid = {29374252}, issn = {1546-1718}, support = {R01 GM036477/GM/NIGMS NIH HHS/United States ; }, } @article {pmid29374247, year = {2018}, author = {Berdugo, M and Kéfi, S and Soliveres, S and Maestre, FT}, title = {Author Correction: Plant spatial patterns identify alternative ecosystem multifunctionality states in global drylands.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {574-576}, doi = {10.1038/s41559-017-0382-5}, pmid = {29374247}, issn = {2397-334X}, abstract = {In the version of this Article originally published, the values of two of the functions used to calculate the multifunctionality index were incorrect, which affected Figs 3,4 of the main article and Supplementary Figs 3,4,5,6,9. Please see the correction notice for full details.}, } @article {pmid29374092, year = {2018}, author = {Dzieran, J and Rodriguez Garcia, A and Westermark, UK and Henley, AB and Eyre Sánchez, E and Träger, C and Johansson, HJ and Lehtiö, J and Arsenian-Henriksson, M}, title = {MYCN-amplified neuroblastoma maintains an aggressive and undifferentiated phenotype by deregulation of estrogen and NGF signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1229-E1238}, pmid = {29374092}, issn = {1091-6490}, mesh = {Animals ; Cell Differentiation ; Estrogen Receptor alpha/genetics/*metabolism ; Estrogens/*pharmacology ; Gene Amplification ; Gene Expression Regulation, Neoplastic/*drug effects ; Humans ; Mice ; N-Myc Proto-Oncogene Protein/*genetics/metabolism ; Nerve Growth Factor/*pharmacology ; Neuroblastoma/genetics/metabolism/*pathology ; Phenotype ; Receptors, Cytoplasmic and Nuclear/genetics/metabolism ; Signal Transduction ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays ; }, abstract = {Neuroblastoma (NB) is a remarkably heterogenic childhood tumor of the sympathetic nervous system with clinical behavior ranging from spontaneous regression to poorly differentiated tumors and metastasis. MYCN is amplified in 20% of cases and correlates with an undifferentiated, aggressive phenotype and poor prognosis. Estrogen receptor alpha (ERα) and the nerve growth factor (NGF) receptors TrkA and p75NTR are involved in neuronal differentiation and survival. We have previously shown that MYCN, via miR-18a, targets ERα in NB cells. Here, we demonstrate that interference with miR-18a or overexpression of ERα is sufficient to induce NGF signaling and to modulate both basal and NGF-induced neuronal differentiation in MYCN-amplified NB cells. Proteomic analysis confirmed an increase of neuronal features and showed that processes linked to tumor initiation and progression were inhibited upon ERα overexpression. Indeed, ectopic ERα expression was sufficient to inhibit metabolic activity and tumorigenic processes, including glycolysis, oxidative phosphorylation, cell viability, migration, and anchorage independent growth. Importantly, ERα overexpression reduced tumor burden in NB mouse models and high ERα levels were linked to improved survival in patients. In addition to ERα, several other nuclear hormone receptors (NHRs), including the glucocorticoid and the retinoic acid receptors, correlated with clinical markers for favorable and low-stage NB disease. Our data suggest that MYCN targets ERα and thereby NGF signaling to maintain an undifferentiated and aggressive phenotype. Notably, we identified the estrogen-NGF crosstalk, as well as a set of other NHRs, as potential prognostic markers and targets for therapeutic strategies against NB.}, } @article {pmid29373999, year = {2018}, author = {Fuks, G and Elgart, M and Amir, A and Zeisel, A and Turnbaugh, PJ and Soen, Y and Shental, N}, title = {Combining 16S rRNA gene variable regions enables high-resolution microbial community profiling.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {17}, pmid = {29373999}, issn = {2049-2618}, support = {R01 HL122593/HL/NHLBI NIH HHS/United States ; 3-11174//Ministry of Science and Technology, Israel/International ; }, mesh = {Algorithms ; Animals ; Bacteria/classification ; Computer Simulation ; DNA Probes/genetics ; DNA, Bacterial/genetics ; Drosophila melanogaster/*microbiology ; Microbiota ; Phylogeny ; Polymerase Chain Reaction/*methods ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Most of our knowledge about the remarkable microbial diversity on Earth comes from sequencing the 16S rRNA gene. The use of next-generation sequencing methods has increased sample number and sequencing depth, but the read length of the most widely used sequencing platforms today is quite short, requiring the researcher to choose a subset of the gene to sequence (typically 16-33% of the total length). Thus, many bacteria may share the same amplified region, and the resolution of profiling is inherently limited. Platforms that offer ultra-long read lengths, whole genome shotgun sequencing approaches, and computational frameworks formerly suggested by us and by others all allow different ways to circumvent this problem yet suffer various shortcomings. There is a need for a simple and low-cost 16S rRNA gene-based profiling approach that harnesses the short read length to provide a much larger coverage of the gene to allow for high resolution, even in harsh conditions of low bacterial biomass and fragmented DNA.

RESULTS: This manuscript suggests Short MUltiple Regions Framework (SMURF), a method to combine sequencing results from different PCR-amplified regions to provide one coherent profiling. The de facto amplicon length is the total length of all amplified regions, thus providing much higher resolution compared to current techniques. Computationally, the method solves a convex optimization problem that allows extremely fast reconstruction and requires only moderate memory. We demonstrate the increase in resolution by in silico simulations and by profiling two mock mixtures and real-world biological samples. Reanalyzing a mock mixture from the Human Microbiome Project achieved about twofold improvement in resolution when combing two independent regions. Using a custom set of six primer pairs spanning about 1200 bp (80%) of the 16S rRNA gene, we were able to achieve ~ 100-fold improvement in resolution compared to a single region, over a mock mixture of common human gut bacterial isolates. Finally, the profiling of a Drosophila melanogaster microbiome using the set of six primer pairs provided a ~ 100-fold increase in resolution and thus enabling efficient downstream analysis.

CONCLUSIONS: SMURF enables the identification of near full-length 16S rRNA gene sequences in microbial communities, having resolution superior compared to current techniques. It may be applied to standard sample preparation protocols with very little modifications. SMURF also paves the way to high-resolution profiling of low-biomass and fragmented DNA, e.g., in the case of formalin-fixed and paraffin-embedded samples, fossil-derived DNA, or DNA exposed to other degrading conditions. The approach is not restricted to combining amplicons of the 16S rRNA gene and may be applied to any set of amplicons, e.g., in multilocus sequence typing (MLST).}, } @article {pmid29373972, year = {2018}, author = {Grapputo, A and Thrimawithana, AH and Steinwender, B and Newcomb, RD}, title = {Differential gene expression in the evolution of sex pheromone communication in New Zealand's endemic leafroller moths of the genera Ctenopseustis and Planotortrix.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {94}, pmid = {29373972}, issn = {1471-2164}, support = {Ex-60% 2016//Ministero dell'Istruzione, dell'Università e della Ricerca (IT)/International ; }, mesh = {Animals ; *Biological Evolution ; Fatty Acid Desaturases/genetics/metabolism ; Female ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; Male ; Moths/classification/*genetics ; New Zealand ; Receptors, Odorant/genetics/metabolism ; Sex Attractants/*metabolism ; Species Specificity ; Transcriptome ; }, abstract = {BACKGROUND: Sex pheromone communication in moths has attracted the attention of evolutionary biologists due to the vast array of pheromone compounds used, addressing questions of how this diversity arose and how male reception has evolved in step with the female signal. Here we examine the role of changing gene expression in the evolution of mate recognition systems in leafroller moths, particularly focusing on genes involved in the biosynthetic pathways of sex pheromones in female pheromone glands and the peripheral reception repertoire in the antennae of males. From tissue-specific transcriptomes we mined and compared a database of genes expressed in the pheromone glands and antennae of males and females of four closely related species of leafroller moths endemic to New Zealand, Ctenopseutis herana and C. obliquana, and Planotortrix excessana and P. octo. The peculiarity of this group, compared to other Lepidoptera, is the use of (Z)-5-tetradecenyl acetate, (Z)-7-tetradecenyl acetate, and (Z)-8-tetradecenyl acetate as sex pheromone components.

RESULTS: We identify orthologues of candidate genes from the pheromone biosynthesis pathway, degradation and transport, as well as genes of the periphery olfactory repertoire, including large families of binding proteins, receptors and odorant degrading enzymes. The production of distinct pheromone blends in the sibling species is associated with the differential expression of two desaturase genes, deast5 and desat7, in the pheromone glands. In male antennae, three odorant receptors, OR74, OR76a and OR30 are over-expressed, but their expression could not be clearly associated with the detection of species-specific pheromones components. In addition these species contain duplications of all three pheromone binding proteins (PBPs) that are also differentially expressed among species.

CONCLUSIONS: While in females differences in the expression of desaturases may be sufficient to explain pheromone blend differences among these New Zealand leafroller species, in males differential expression of several genes, including pheromone binding proteins, may underpin differences in the response by males to changing pheromone components among the species.}, } @article {pmid29373957, year = {2018}, author = {Naidoo, T and Sjödin, P and Schlebusch, C and Jakobsson, M}, title = {Patterns of variation in cis-regulatory regions: examining evidence of purifying selection.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {95}, pmid = {29373957}, issn = {1471-2164}, mesh = {Evolution, Molecular ; Gene Expression Regulation ; *Genetic Variation ; *Genetics, Population ; *Genome, Human ; Humans ; *Open Reading Frames ; Polymorphism, Single Nucleotide ; *Regulatory Sequences, Nucleic Acid ; *Selection, Genetic ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: With only 2 % of the human genome consisting of protein coding genes, functionality across the rest of the genome has been the subject of much debate. This has gained further impetus in recent years due to a rapidly growing catalogue of genomic elements, based primarily on biochemical signatures (e.g. the ENCODE project). While the assessment of functionality is a complex task, the presence of selection acting on a genomic region is a strong indicator of importance. In this study, we apply population genetic methods to investigate signals overlaying several classes of regulatory elements.

RESULTS: We disentangle signals of purifying selection acting directly on regulatory elements from the confounding factors of demography and purifying selection linked to e.g. nearby protein coding regions. We confirm the importance of regulatory regions proximal to coding sequence, while also finding differential levels of selection at distal regions. We note differences in purifying selection among transcription factor families. Signals of constraint at some genomic classes were also strongly dependent on their physical location relative to coding sequence. In addition, levels of selection efficacy across genomic classes differed between African and non-African populations.

CONCLUSIONS: In order to assign a valid signal of selection to a particular class of genomic sequence, we show that it is crucial to isolate the signal by accounting for the effects of demography and linked-purifying selection. Our study highlights the intricate interplay of factors affecting signals of selection on functional elements.}, } @article {pmid29373955, year = {2018}, author = {Prytuliak, R and Pfeiffer, F and Habermann, BH}, title = {SLALOM, a flexible method for the identification and statistical analysis of overlapping continuous sequence elements in sequence- and time-series data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {24}, pmid = {29373955}, issn = {1471-2105}, mesh = {Archaea/genetics ; Computational Biology/*methods ; Molecular Sequence Annotation ; Open Reading Frames/genetics ; Proteins/chemistry ; }, abstract = {BACKGROUND: Protein or nucleic acid sequences contain a multitude of associated annotations representing continuous sequence elements (CSEs). Comparing these CSEs is needed, whenever we want to match identical annotations or integrate distinctive ones. Currently, there is no ready-to-use software available that provides comprehensive statistical readout for comparing two annotations of the same type with each other, which can be adapted to the application logic of the scientific question.

RESULTS: We have developed a method, SLALOM (for StatisticaL Analysis of Locus Overlap Method), to perform comparative analysis of sequence annotations in a highly flexible way. SLALOM implements six major operation modes and a number of additional options that can answer a variety of statistical questions about a pair of input annotations of a given sequence collection. We demonstrate the results of SLALOM on three different examples from biology and economics and compare our method to already existing software. We discuss the importance of carefully choosing the application logic to address specific scientific questions.

CONCLUSION: SLALOM is a highly versatile, command-line based method for comparing annotations in a collection of sequences, with a statistical read-out for performance evaluation and benchmarking of predictors and gene annotation pipelines. Abstraction from sequence content even allows SLALOM to compare other kinds of positional data including, for example, data coming from time series.}, } @article {pmid29373953, year = {2018}, author = {Zhang, Q and Oh, DH and DiTusa, SF and RamanaRao, MV and Baisakh, N and Dassanayake, M and Smith, AP}, title = {Rice nucleosome patterns undergo remodeling coincident with stress-induced gene expression.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {97}, pmid = {29373953}, issn = {1471-2164}, support = {IOS-1127051//Directorate for Biological Sciences/International ; MCB-1616827//Directorate for Biological Sciences/International ; PJ011379//Rural Development Administration/International ; }, mesh = {*Chromatin Assembly and Disassembly ; *Gene Expression Regulation, Plant ; *Nucleosomes ; Oryza/*genetics/physiology ; Sequence Analysis, RNA/methods ; Stress, Physiological ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Formation of nucleosomes along eukaryotic DNA has an impact on transcription. Major transcriptional changes occur in response to low external phosphate (Pi) in plants, but the involvement of chromatin-level mechanisms in Pi starvation responses have not been investigated.

RESULTS: We mapped nucleosomes along with transcriptional changes after 24-h of Pi starvation in rice (Oryza sativa) by deep sequencing of micrococcal nuclease digested chromatin and ribosome-depleted RNA. We demonstrated that nucleosome patterns at rice genes were affected by both cis- and trans-determinants, including GC content and transcription. Also, categorizing rice genes by nucleosome patterns across the transcription start site (TSS) revealed nucleosome patterns that correlated with distinct functional categories of genes. We further demonstrated that Pi starvation resulted in numerous dynamic nucleosomes, which were enhanced at genes differentially expressed in response to Pi starvation.

CONCLUSIONS: We demonstrate that rice nucleosome patterns are suggestive of gene functions, and reveal a link between chromatin remodeling and transcriptional changes in response to deficiency of a major macronutrient. Our findings help to enhance the understanding towards eukaryotic gene regulation at the chromatin level.}, } @article {pmid29373712, year = {2018}, author = {Achim, K and Eling, N and Vergara, HM and Bertucci, PY and Musser, J and Vopalensky, P and Brunet, T and Collier, P and Benes, V and Marioni, JC and Arendt, D}, title = {Whole-Body Single-Cell Sequencing Reveals Transcriptional Domains in the Annelid Larval Body.}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1047-1062}, pmid = {29373712}, issn = {1537-1719}, abstract = {Animal bodies comprise diverse arrays of cells. To characterize cellular identities across an entire body, we have compared the transcriptomes of single cells randomly picked from dissociated whole larvae of the marine annelid Platynereis dumerilii. We identify five transcriptionally distinct groups of differentiated cells, each expressing a unique set of transcription factors and effector genes that implement cellular phenotypes. Spatial mapping of cells into a cellular expression atlas, and wholemount in situ hybridization of group-specific genes reveals spatially coherent transcriptional domains in the larval body, comprising, for example, apical sensory-neurosecretory cells versus neural/epidermal surface cells. These domains represent new, basic subdivisions of the annelid body based entirely on differential gene expression, and are composed of multiple, transcriptionally similar cell types. They do not represent clonal domains, as revealed by developmental lineage analysis. We propose that the transcriptional domains that subdivide the annelid larval body represent families of related cell types that have arisen by evolutionary diversification. Their possible evolutionary conservation makes them a promising tool for evo-devo research.}, } @article {pmid29373668, year = {2018}, author = {Liang, C and Musser, JM and Cloutier, A and Prum, RO and Wagner, GP}, title = {Pervasive Correlated Evolution in Gene Expression Shapes Cell and Tissue Type Transcriptomes.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {538-552}, pmid = {29373668}, issn = {1759-6653}, mesh = {Animals ; Cattle ; Chickens ; Cluster Analysis ; Computer Simulation ; *Evolution, Molecular ; *Gene Expression Profiling ; Macaca mulatta ; Mice ; Models, Genetic ; Phylogeny ; Rats ; Stochastic Processes ; *Transcriptome ; }, abstract = {The evolution and diversification of cell types is a key means by which animal complexity evolves. Recently, hierarchical clustering and phylogenetic methods have been applied to RNA-seq data to infer cell type evolutionary history and homology. A major challenge for interpreting this data is that cell type transcriptomes may not evolve independently due to correlated changes in gene expression. This nonindependence can arise for several reasons, such as common regulatory sequences for genes expressed in multiple tissues, that is, pleiotropic effects of mutations. We develop a model to estimate the level of correlated transcriptome evolution (LCE) and apply it to different data sets. The results reveal pervasive correlated transcriptome evolution among different cell and tissue types. In general, tissues related by morphology or developmental lineage exhibit higher LCE than more distantly related tissues. Analyzing new data collected from bird skin appendages suggests that LCE decreases with the phylogenetic age of tissues compared, with recently evolved tissues exhibiting the highest LCE. Furthermore, we show correlated evolution can alter patterns of hierarchical clustering, causing different tissue types from the same species to cluster together. To identify genes that most strongly contribute to the correlated evolution signal, we performed a gene-wise estimation of LCE on a data set with ten species. Removing genes with high LCE allows for accurate reconstruction of evolutionary relationships among tissue types. Our study provides a statistical method to measure and account for correlated gene expression evolution when interpreting comparative transcriptome data.}, } @article {pmid29373257, year = {2018}, author = {Klemm, C and Boergeling, Y and Ludwig, S and Ehrhardt, C}, title = {Immunomodulatory Nonstructural Proteins of Influenza A Viruses.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {624-636}, doi = {10.1016/j.tim.2017.12.006}, pmid = {29373257}, issn = {1878-4380}, abstract = {Influenza epidemics and pandemics still represent a severe public health threat and cause significant morbidity and mortality worldwide. As intracellular parasites, influenza viruses are strongly dependent on the host cell machinery. To ensure efficient production of progeny viruses, viral proteins extensively interfere with cellular signalling pathways to inhibit antiviral responses or to activate virus-supportive functions. Here, we review various functions of the influenza virus nonstructural proteins NS1, PB1-F2, and PA-X in infected cells and how post-transcriptional modifications of these proteins affect the viral life cycle. Furthermore, we discuss newly discovered interactions between these proteins and the antiviral interferon response.}, } @article {pmid29372584, year = {2018}, author = {Rice, G and Barmina, O and Hu, K and Kopp, A}, title = {Evolving doublesex expression correlates with the origin and diversification of male sexual ornaments in the Drosophila immigrans species group.}, journal = {Evolution & development}, volume = {20}, number = {2}, pages = {78-88}, doi = {10.1111/ede.12249}, pmid = {29372584}, issn = {1525-142X}, support = {R01 GM105726/GM/NIGMS NIH HHS/United States ; R35 GM122592/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Biological Evolution ; DNA-Binding Proteins/genetics/*metabolism ; Drosophila/*classification/*physiology ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/physiology ; Extremities/physiology ; Female ; *Gene Expression Regulation ; Male ; Phylogeny ; Sexual Behavior, Animal ; }, abstract = {Male ornaments and other sex-specific traits present some of the most dramatic examples of evolutionary innovations. Comparative studies of similar but independently evolved traits are particularly important for identifying repeated patterns in the evolution of these traits. Male-specific modifications of the front legs have evolved repeatedly in Drosophilidae and other Diptera. The best understood of these novel structures is the sex comb of Drosophila melanogaster and its close relatives. Here, we examine the evolution of another male foreleg modification, the sex brush, found in the distantly related Drosophila immigrans species group. Similar to the sex comb, we find that the origin of the sex brush correlates with novel, spatially restricted expression of the doublesex (dsx) transcription factor, the primary effector of the Drosophila sex determination pathway. The diversity of Dsx expression patterns in the immigrans species group closely reflects the differences in the presence, position, and size of the sex brush. Together with previous work on sex comb evolution, these observations suggest that tissue-specific activation of dsx expression may be a common mechanism responsible for the evolution of sexual dimorphism and particularly for the origin of novel male-specific ornaments.}, } @article {pmid29371910, year = {2018}, author = {Harunari, E and Komaki, H and Ichikawa, N and Hosoyama, A and Kimura, A and Hamada, M and Igarashi, Y}, title = {Draft genome sequence of Streptomyces hyaluromycini MB-PO13T, a hyaluromycin producer.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {2}, pmid = {29371910}, issn = {1944-3277}, abstract = {Streptomyces hyaluromycini MB-PO13T (=NBRC 110483T = DSM 100105T) is type strain of the species, which produces a hyaluronidase inhibitor, hyaluromycin. Here, we report the draft genome sequence of this strain together with features of the organism and generation, annotation and analysis of the genome sequence. The 11.5 Mb genome of Streptomyces hyaluromycini MB-PO13T encoded 10,098 putative ORFs, of which 5317 were assigned with COG categories. The genome harbored at least six type I PKS clusters, three type II PKS gene clusters, two type III PKS gene clusters, six NRPS gene clusters, and one hybrid PKS/NRPS gene cluster. The type II PKS gene cluster including 2-amino-3-hydroxycyclopent-2-enone synthetic genes was identified to be responsible for hyaluromycin synthesis. We propose the biosynthetic pathway based on bioinformatic analysis.}, } @article {pmid29371472, year = {2018}, author = {Boehnke, KF}, title = {Cheating on my mentor.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {486}, doi = {10.1126/science.359.6374.486}, pmid = {29371472}, issn = {1095-9203}, } @article {pmid29371471, year = {2018}, author = {Tucker, MA and Böhning-Gaese, K and Fagan, WF and Fryxell, JM and Van Moorter, B and Alberts, SC and Ali, AH and Allen, AM and Attias, N and Avgar, T and Bartlam-Brooks, H and Bayarbaatar, B and Belant, JL and Bertassoni, A and Beyer, D and Bidner, L and van Beest, FM and Blake, S and Blaum, N and Bracis, C and Brown, D and de Bruyn, PJN and Cagnacci, F and Calabrese, JM and Camilo-Alves, C and Chamaillé-Jammes, S and Chiaradia, A and Davidson, SC and Dennis, T and DeStefano, S and Diefenbach, D and Douglas-Hamilton, I and Fennessy, J and Fichtel, C and Fiedler, W and Fischer, C and Fischhoff, I and Fleming, CH and Ford, AT and Fritz, SA and Gehr, B and Goheen, JR and Gurarie, E and Hebblewhite, M and Heurich, M and Hewison, AJM and Hof, C and Hurme, E and Isbell, LA and Janssen, R and Jeltsch, F and Kaczensky, P and Kane, A and Kappeler, PM and Kauffman, M and Kays, R and Kimuyu, D and Koch, F and Kranstauber, B and LaPoint, S and Leimgruber, P and Linnell, JDC and López-López, P and Markham, AC and Mattisson, J and Medici, EP and Mellone, U and Merrill, E and de Miranda Mourão, G and Morato, RG and Morellet, N and Morrison, TA and Díaz-Muñoz, SL and Mysterud, A and Nandintsetseg, D and Nathan, R and Niamir, A and Odden, J and O'Hara, RB and Oliveira-Santos, LGR and Olson, KA and Patterson, BD and Cunha de Paula, R and Pedrotti, L and Reineking, B and Rimmler, M and Rogers, TL and Rolandsen, CM and Rosenberry, CS and Rubenstein, DI and Safi, K and Saïd, S and Sapir, N and Sawyer, H and Schmidt, NM and Selva, N and Sergiel, A and Shiilegdamba, E and Silva, JP and Singh, N and Solberg, EJ and Spiegel, O and Strand, O and Sundaresan, S and Ullmann, W and Voigt, U and Wall, J and Wattles, D and Wikelski, M and Wilmers, CC and Wilson, JW and Wittemyer, G and Zięba, F and Zwijacz-Kozica, T and Mueller, T}, title = {Moving in the Anthropocene: Global reductions in terrestrial mammalian movements.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {466-469}, doi = {10.1126/science.aam9712}, pmid = {29371471}, issn = {1095-9203}, mesh = {*Animal Migration ; Animals ; Geographic Information Systems ; *Human Activities ; Humans ; *Mammals ; }, abstract = {Animal movement is fundamental for ecosystem functioning and species survival, yet the effects of the anthropogenic footprint on animal movements have not been estimated across species. Using a unique GPS-tracking database of 803 individuals across 57 species, we found that movements of mammals in areas with a comparatively high human footprint were on average one-half to one-third the extent of their movements in areas with a low human footprint. We attribute this reduction to behavioral changes of individual animals and to the exclusion of species with long-range movements from areas with higher human impact. Global loss of vagility alters a key ecological trait of animals that affects not only population persistence but also ecosystem processes such as predator-prey interactions, nutrient cycling, and disease transmission.}, } @article {pmid29371470, year = {2018}, author = {Ni, AM and Ruff, DA and Alberts, JJ and Symmonds, J and Cohen, MR}, title = {Learning and attention reveal a general relationship between population activity and behavior.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {463-465}, doi = {10.1126/science.aao0284}, pmid = {29371470}, issn = {1095-9203}, support = {R00 EY020844/EY/NEI NIH HHS/United States ; R01 EY022930/EY/NEI NIH HHS/United States ; P30 EY008098/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; Attention/*physiology ; Behavior/*physiology ; Evoked Potentials ; Haplorhini ; Learning/*physiology ; Male ; Neurons/*physiology ; Perception/*physiology ; }, abstract = {Prior studies have demonstrated that correlated variability changes with cognitive processes that improve perceptual performance. We tested whether correlated variability covaries with subjects' performance-whether performance improves quickly with attention or slowly with perceptual learning. We found a single, consistent relationship between correlated variability and behavioral performance, regardless of the time frame of correlated variability change. This correlated variability was oriented along the dimensions in population space used by the animal on a trial-by-trial basis to make decisions. That subjects' choices were predicted by specific dimensions that were aligned with the correlated variability axis clarifies long-standing paradoxes about the relationship between shared variability and behavior.}, } @article {pmid29371469, year = {2018}, author = {Lamb, JB and Willis, BL and Fiorenza, EA and Couch, CS and Howard, R and Rader, DN and True, JD and Kelly, LA and Ahmad, A and Jompa, J and Harvell, CD}, title = {Plastic waste associated with disease on coral reefs.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {460-462}, doi = {10.1126/science.aar3320}, pmid = {29371469}, issn = {1095-9203}, mesh = {*Coral Reefs ; *Plastics ; *Refuse Disposal ; }, abstract = {Plastic waste can promote microbial colonization by pathogens implicated in outbreaks of disease in the ocean. We assessed the influence of plastic waste on disease risk in 124,000 reef-building corals from 159 reefs in the Asia-Pacific region. The likelihood of disease increases from 4% to 89% when corals are in contact with plastic. Structurally complex corals are eight times more likely to be affected by plastic, suggesting that microhabitats for reef-associated organisms and valuable fisheries will be disproportionately affected. Plastic levels on coral reefs correspond to estimates of terrestrial mismanaged plastic waste entering the ocean. We estimate that 11.1 billion plastic items are entangled on coral reefs across the Asia-Pacific and project this number to increase 40% by 2025. Plastic waste management is critical for reducing diseases that threaten ecosystem health and human livelihoods.}, } @article {pmid29371468, year = {2018}, author = {Hershkovitz, I and Weber, GW and Quam, R and Duval, M and Grün, R and Kinsley, L and Ayalon, A and Bar-Matthews, M and Valladas, H and Mercier, N and Arsuaga, JL and Martinón-Torres, M and Bermúdez de Castro, JM and Fornai, C and Martín-Francés, L and Sarig, R and May, H and Krenn, VA and Slon, V and Rodríguez, L and García, R and Lorenzo, C and Carretero, JM and Frumkin, A and Shahack-Gross, R and Bar-Yosef Mayer, DE and Cui, Y and Wu, X and Peled, N and Groman-Yaroslavski, I and Weissbrod, L and Yeshurun, R and Tsatskin, A and Zaidner, Y and Weinstein-Evron, M}, title = {The earliest modern humans outside Africa.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {456-459}, doi = {10.1126/science.aap8369}, pmid = {29371468}, issn = {1095-9203}, mesh = {Africa ; *Biological Evolution ; Caves ; Dentition ; Fossils ; History, Ancient ; Human Migration/*history ; Humans ; Israel ; Maxilla ; Technology/history ; }, abstract = {To date, the earliest modern human fossils found outside of Africa are dated to around 90,000 to 120,000 years ago at the Levantine sites of Skhul and Qafzeh. A maxilla and associated dentition recently discovered at Misliya Cave, Israel, was dated to 177,000 to 194,000 years ago, suggesting that members of the Homo sapiens clade left Africa earlier than previously thought. This finding changes our view on modern human dispersal and is consistent with recent genetic studies, which have posited the possibility of an earlier dispersal of Homo sapiens around 220,000 years ago. The Misliya maxilla is associated with full-fledged Levallois technology in the Levant, suggesting that the emergence of this technology is linked to the appearance of Homo sapiens in the region, as has been documented in Africa.}, } @article {pmid29371467, year = {2018}, author = {Wu, Z and Ahmad, R and Yin, B and Sandlöbes, S and Curtin, WA}, title = {Mechanistic origin and prediction of enhanced ductility in magnesium alloys.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {447-452}, doi = {10.1126/science.aap8716}, pmid = {29371467}, issn = {1095-9203}, abstract = {Pure magnesium exhibits poor ductility owing to pyramidal [Formula: see text] dislocation transformations to immobile structures, making this lowest-density structural metal unusable for many applications where it could enhance energy efficiency. We show why magnesium can be made ductile by specific dilute solute additions, which increase the [Formula: see text] cross-slip and multiplication rates to levels much faster than the deleterious [Formula: see text] transformation, enabling both favorable texture during processing and continued plastic straining during deformation. A quantitative theory establishes the conditions for ductility as a function of alloy composition in very good agreement with experiments on many existing magnesium alloys, and the solute-enhanced cross-slip mechanism is confirmed by transmission electron microscopy observations in magnesium-yttrium. The mechanistic theory can quickly screen for alloy compositions favoring conditions for high ductility and may help in the development of high-formability magnesium alloys.}, } @article {pmid29371466, year = {2018}, author = {Gong, SH and Alpeggiani, F and Sciacca, B and Garnett, EC and Kuipers, L}, title = {Nanoscale chiral valley-photon interface through optical spin-orbit coupling.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {443-447}, doi = {10.1126/science.aan8010}, pmid = {29371466}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The emergence of two-dimensional transition metal dichalcogenide materials has sparked intense activity in valleytronics, as their valley information can be encoded and detected with the spin angular momentum of light. We demonstrate the valley-dependent directional coupling of light using a plasmonic nanowire-tungsten disulfide (WS2) layers system. We show that the valley pseudospin in WS2 couples to transverse optical spin of the same handedness with a directional coupling efficiency of 90 ± 1%. Our results provide a platform for controlling, detecting, and processing valley and spin information with precise optical control at the nanoscale.}, } @article {pmid29371465, year = {2018}, author = {Koga, Y and Kaneda, T and Saito, Y and Murakami, K and Itami, K}, title = {Synthesis of partially and fully fused polyaromatics by annulative chlorophenylene dimerization.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {435-439}, doi = {10.1126/science.aap9801}, pmid = {29371465}, issn = {1095-9203}, abstract = {Since the discovery by Ullmann and Bielecki in 1901, reductive dimerization (or homocoupling) of aryl halides has been extensively exploited for the generation of a range of biaryl-based functional molecules. In contrast to the single-point connection in these products, edge-sharing fused aromatic systems have not generally been accessible from simple aryl halides via annulation cascades. Here we report a single-step synthesis of fused aromatics with a triphenylene core by the palladium-catalyzed annulative dimerization of structurally and functionally diverse chlorophenylenes through double carbon-hydrogen bond activation. The partially fused polyaromatics can be transformed into fully fused, small graphene nanoribbons, which are otherwise difficult to synthesize. This simple, yet powerful, method allows access to functional π-systems of interest in optoelectronics research.}, } @article {pmid29371464, year = {2018}, author = {Perera, D and Tucker, JW and Brahmbhatt, S and Helal, CJ and Chong, A and Farrell, W and Richardson, P and Sach, NW}, title = {A platform for automated nanomole-scale reaction screening and micromole-scale synthesis in flow.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {429-434}, doi = {10.1126/science.aap9112}, pmid = {29371464}, issn = {1095-9203}, abstract = {The scarcity of complex intermediates in pharmaceutical research motivates the pursuit of reaction optimization protocols on submilligram scales. We report here the development of an automated flow-based synthesis platform, designed from commercially available components, that integrates both rapid nanomole-scale reaction screening and micromole-scale synthesis into a single modular unit. This system was validated by exploring a diverse range of reaction variables in a Suzuki-Miyaura coupling on nanomole scale at elevated temperatures, generating liquid chromatography-mass spectrometry data points for 5760 reactions at a rate of >1500 reactions per 24 hours. Through multiple injections of the same segment, the system directly produced micromole quantities of desired material. The optimal conditions were also replicated in traditional flow and batch mode at 50- to 200-milligram scale to provide good to excellent yields.}, } @article {pmid29371463, year = {2018}, author = {Kong, A and Thorleifsson, G and Frigge, ML and Vilhjalmsson, BJ and Young, AI and Thorgeirsson, TE and Benonisdottir, S and Oddsson, A and Halldorsson, BV and Masson, G and Gudbjartsson, DF and Helgason, A and Bjornsdottir, G and Thorsteinsdottir, U and Stefansson, K}, title = {The nature of nurture: Effects of parental genotypes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {424-428}, doi = {10.1126/science.aan6877}, pmid = {29371463}, issn = {1095-9203}, mesh = {Alleles ; Child ; *Child Development ; Educational Status ; Fathers/*psychology ; Female ; Genomics ; Genotype ; Humans ; Male ; *Maternal Behavior ; Mothers/*psychology ; *Multifactorial Inheritance ; Parent-Child Relations ; *Paternal Behavior ; }, abstract = {Sequence variants in the parental genomes that are not transmitted to a child (the proband) are often ignored in genetic studies. Here we show that nontransmitted alleles can affect a child through their impacts on the parents and other relatives, a phenomenon we call "genetic nurture." Using results from a meta-analysis of educational attainment, we find that the polygenic score computed for the nontransmitted alleles of 21,637 probands with at least one parent genotyped has an estimated effect on the educational attainment of the proband that is 29.9% (P = 1.6 × 10-14) of that of the transmitted polygenic score. Genetic nurturing effects of this polygenic score extend to other traits. Paternal and maternal polygenic scores have similar effects on educational attainment, but mothers contribute more than fathers to nutrition- and heath-related traits.}, } @article {pmid29371462, year = {2018}, author = {Fan, J and Rosenfeld, D and Zhang, Y and Giangrande, SE and Li, Z and Machado, LAT and Martin, ST and Yang, Y and Wang, J and Artaxo, P and Barbosa, HMJ and Braga, RC and Comstock, JM and Feng, Z and Gao, W and Gomes, HB and Mei, F and Pöhlker, C and Pöhlker, ML and Pöschl, U and de Souza, RAF}, title = {Substantial convection and precipitation enhancements by ultrafine aerosol particles.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {411-418}, doi = {10.1126/science.aan8461}, pmid = {29371462}, issn = {1095-9203}, abstract = {Aerosol-cloud interactions remain the largest uncertainty in climate projections. Ultrafine aerosol particles smaller than 50 nanometers (UAP<50) can be abundant in the troposphere but are conventionally considered too small to affect cloud formation. Observational evidence and numerical simulations of deep convective clouds (DCCs) over the Amazon show that DCCs forming in a low-aerosol environment can develop very large vapor supersaturation because fast droplet coalescence reduces integrated droplet surface area and subsequent condensation. UAP<50 from pollution plumes that are ingested into such clouds can be activated to form additional cloud droplets on which excess supersaturation condenses and forms additional cloud water and latent heating, thus intensifying convective strength. This mechanism suggests a strong anthropogenic invigoration of DCCs in previously pristine regions of the world.}, } @article {pmid29371461, year = {2018}, author = {Dehaene, S and Lau, H and Kouider, S}, title = {Response.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {400-402}, doi = {10.1126/science.aar8639}, pmid = {29371461}, issn = {1095-9203}, } @article {pmid29371460, year = {2018}, author = {Spatola, N and Urbanska, K}, title = {Conscious machines: Robot rights.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {400}, doi = {10.1126/science.aar5059}, pmid = {29371460}, issn = {1095-9203}, mesh = {*Consciousness ; Humans ; *Robotics ; }, } @article {pmid29371459, year = {2018}, author = {Carter, O and Hohwy, J and van Boxtel, J and Lamme, V and Block, N and Koch, C and Tsuchiya, N}, title = {Conscious machines: Defining questions.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {400}, doi = {10.1126/science.aar4163}, pmid = {29371459}, issn = {1095-9203}, mesh = {*Consciousness ; Humans ; }, } @article {pmid29371458, year = {2018}, author = {Brantley, SL and Vidic, RD and Brasier, K and Yoxtheimer, D and Pollak, J and Wilderman, C and Wen, T}, title = {Engaging over data on fracking and water quality.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {395-397}, doi = {10.1126/science.aan6520}, pmid = {29371458}, issn = {1095-9203}, mesh = {Humans ; *Hydraulic Fracking ; Methane/*analysis ; Water/*chemistry ; *Water Quality ; }, } @article {pmid29371457, year = {2018}, author = {Schreiber, LR and Bluhm, H}, title = {Toward a silicon-based quantum computer.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {393-394}, doi = {10.1126/science.aar6209}, pmid = {29371457}, issn = {1095-9203}, mesh = {Computers ; *Equipment Design ; Quantum Dots ; *Silicon ; }, } @article {pmid29371456, year = {2018}, author = {Geldmann, J and González-Varo, JP}, title = {Conserving honey bees does not help wildlife.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {392-393}, doi = {10.1126/science.aar2269}, pmid = {29371456}, issn = {1095-9203}, mesh = {Animals ; Beekeeping/*methods ; *Bees ; *Conservation of Natural Resources ; Crops, Agricultural ; Pollination ; Population ; }, } @article {pmid29371455, year = {2018}, author = {Fry, MY and Clemons, WM}, title = {Complexity in targeting membrane proteins.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {390-391}, doi = {10.1126/science.aar5992}, pmid = {29371455}, issn = {1095-9203}, support = {R01 GM097572/GM/NIGMS NIH HHS/United States ; }, mesh = {*Cell Membrane ; *Membrane Proteins ; Recombinant Fusion Proteins ; }, } @article {pmid29371454, year = {2018}, author = {Stringer, C and Galway-Witham, J}, title = {When did modern humans leave Africa?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {389-390}, doi = {10.1126/science.aas8954}, pmid = {29371454}, issn = {1095-9203}, mesh = {Africa ; Animals ; *Biological Evolution ; *Hominidae ; Humans ; }, } @article {pmid29371453, year = {2018}, author = {Saliba, M}, title = {Perovskite solar cells must come of age.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {388-389}, doi = {10.1126/science.aar5684}, pmid = {29371453}, issn = {1095-9203}, } @article {pmid29371452, year = {2018}, author = {Koellinger, PD and Harden, KP}, title = {Using nature to understand nurture.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {386-387}, doi = {10.1126/science.aar6429}, pmid = {29371452}, issn = {1095-9203}, support = {647648//European Research Council/International ; }, mesh = {*Environment ; Humans ; }, } @article {pmid29371451, year = {2018}, author = {Cartlidge, E}, title = {The light fantastic.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {382-385}, doi = {10.1126/science.359.6374.382}, pmid = {29371451}, issn = {1095-9203}, } @article {pmid29371450, year = {2018}, author = {Cho, A}, title = {Muon's magnetism could point to new physics.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {381}, doi = {10.1126/science.359.6374.381}, pmid = {29371450}, issn = {1095-9203}, } @article {pmid29371449, year = {2018}, author = {Kornei, K}, title = {Australian state forecasts deadly thunderstorm asthma.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {380}, doi = {10.1126/science.359.6374.380}, pmid = {29371449}, issn = {1095-9203}, mesh = {Asthma/*etiology ; Australia ; Humans ; Pollen/*adverse effects ; *Wind ; }, } @article {pmid29371448, year = {2018}, author = {McTighe, K}, title = {Crackdown threatens science in Turkey.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {378-379}, doi = {10.1126/science.359.6374.378}, pmid = {29371448}, issn = {1095-9203}, } @article {pmid29371447, year = {2018}, author = {Guglielmi, G}, title = {In thousands of brain scans, group seeks clues to diseases.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {377-378}, doi = {10.1126/science.359.6374.377}, pmid = {29371447}, issn = {1095-9203}, mesh = {Brain/*diagnostic imaging ; Epilepsy/*diagnostic imaging ; Humans ; *Magnetic Resonance Imaging ; *Neuroimaging ; }, } @article {pmid29371446, year = {2018}, author = {Mann, A}, title = {Heavy-lift rocket poised to boost space science.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {376-377}, doi = {10.1126/science.359.6374.376}, pmid = {29371446}, issn = {1095-9203}, } @article {pmid29371445, year = {2018}, author = {Kupferschmidt, K}, title = {Critics see only risks, no benefits in horsepox paper.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {375-376}, doi = {10.1126/science.359.6374.375}, pmid = {29371445}, issn = {1095-9203}, mesh = {Humans ; Orthopoxvirus/*immunology ; Risk ; Smallpox/*prevention & control ; Smallpox Vaccine/*adverse effects/*immunology ; }, } @article {pmid29371444, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {372-374}, doi = {10.1126/science.359.6374.372}, pmid = {29371444}, issn = {1095-9203}, } @article {pmid29371443, year = {2018}, author = {Holt, R}, title = {A tale of two cultures.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {371}, doi = {10.1126/science.aat0588}, pmid = {29371443}, issn = {1095-9203}, } @article {pmid29371442, year = {2018}, author = {Siepielski, AM and Morrissey, MB and Buoro, M and Carlson, SM and Caruso, CM and Clegg, SM and Coulson, T and DiBattista, J and Gotanda, KM and Francis, CD and Hereford, J and Kingsolver, JG and Augustine, KE and Kruuk, LEB and Martin, RA and Sheldon, BC and Sletvold, N and Svensson, EI and Wade, MJ and MacColl, ADC}, title = {Response to Comment on "Precipitation drives global variation in natural selection".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {}, doi = {10.1126/science.aan5760}, pmid = {29371442}, issn = {1095-9203}, mesh = {*Climate ; Climate Change ; *Selection, Genetic ; }, abstract = {The comment by Myers-Smith and Myers focuses on three main points: (i) the lack of a mechanistic explanation for climate-selection relationships, (ii) the appropriateness of the climate data used in our analysis, and (iii) our focus on estimating climate-selection relationships across (rather than within) taxonomic groups. We address these critiques in our response.}, } @article {pmid29371441, year = {2018}, author = {Myers-Smith, IH and Myers, JH}, title = {Comment on "Precipitation drives global variation in natural selection".}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {}, doi = {10.1126/science.aan5028}, pmid = {29371441}, issn = {1095-9203}, mesh = {Animals ; *Climate ; Invertebrates ; Plants ; *Selection, Genetic ; Vertebrates ; }, abstract = {Siepielski et al (Reports, 3 March 2017, p. 959) claim that "precipitation drives global variation in natural selection." This conclusion is based on a meta-analysis of the relationship between climate variables and natural selection measured in wild populations of invertebrates, plants, and vertebrates. Three aspects of this analysis cause concern: (i) lack of within-year climate variables, (ii) low and variable estimates of covariance relationships across taxa, and (iii) a lack of mechanistic explanations for the patterns observed; association is not causation.}, } @article {pmid29371440, year = {2018}, author = {Madeo, F and Eisenberg, T and Pietrocola, F and Kroemer, G}, title = {Spermidine in health and disease.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {}, doi = {10.1126/science.aan2788}, pmid = {29371440}, issn = {1095-9203}, mesh = {*Aging ; Animals ; Anti-Inflammatory Agents, Non-Steroidal/pharmacology ; Autophagy/drug effects/*physiology ; Biological Transport ; *Caloric Restriction ; Carcinogenesis/metabolism ; Cardiovascular Diseases/prevention & control ; *Dietary Supplements ; Humans ; Metabolic Syndrome/prevention & control ; Neuroprotective Agents/pharmacology ; *Spermidine/administration & dosage/metabolism/pharmacology ; }, abstract = {Interventions that delay aging and protect from age-associated disease are slowly approaching clinical implementation. Such interventions include caloric restriction mimetics, which are defined as agents that mimic the beneficial effects of dietary restriction while limiting its detrimental effects. One such agent, the natural polyamine spermidine, has prominent cardioprotective and neuroprotective effects and stimulates anticancer immunosurveillance in rodent models. Moreover, dietary polyamine uptake correlates with reduced cardiovascular and cancer-related mortality in human epidemiological studies. Spermidine preserves mitochondrial function, exhibits anti-inflammatory properties, and prevents stem cell senescence. Mechanistically, it shares the molecular pathways engaged by other caloric restriction mimetics: It induces protein deacetylation and depends on functional autophagy. Because spermidine is already present in daily human nutrition, clinical trials aiming at increasing the uptake of this polyamine appear feasible.}, } @article {pmid29371429, year = {2018}, author = {Kim, Y and Chen, J}, title = {Molecular structure of human P-glycoprotein in the ATP-bound, outward-facing conformation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {915-919}, doi = {10.1126/science.aar7389}, pmid = {29371429}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {ATP Binding Cassette Transporter, Subfamily B/chemistry/genetics/ultrastructure ; Adenosine Triphosphate/*chemistry ; Crystallography, X-Ray ; Humans ; Hydrolysis ; Mutation ; Protein Domains ; Recombinant Proteins/chemistry/genetics/ultrastructure ; Substrate Specificity ; }, abstract = {The multidrug transporter permeability (P)-glycoprotein is an adenosine triphosphate (ATP)-binding cassette exporter responsible for clinical resistance to chemotherapy. P-glycoprotein extrudes toxic molecules and drugs from cells through ATP-powered conformational changes. Despite decades of effort, only the structures of the inward-facing conformation of P-glycoprotein are available. Here we present the structure of human P-glycoprotein in the outward-facing conformation, determined by cryo-electron microscopy at 3.4-angstrom resolution. The two nucleotide-binding domains form a closed dimer occluding two ATP molecules. The drug-binding cavity observed in the inward-facing structures is reorientated toward the extracellular space and compressed to preclude substrate binding. This observation indicates that ATP binding, not hydrolysis, promotes substrate release. The structure evokes a model in which the dynamic nature of P-glycoprotein enables translocation of a large variety of substrates.}, } @article {pmid29371428, year = {2018}, author = {Tu, YH and Cooper, AJ and Teng, B and Chang, RB and Artiga, DJ and Turner, HN and Mulhall, EM and Ye, W and Smith, AD and Liman, ER}, title = {An evolutionarily conserved gene family encodes proton-selective ion channels.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1047-1050}, pmid = {29371428}, issn = {1095-9203}, support = {R01 DC013741/DC/NIDCD NIH HHS/United States ; R01 HG006015/HG/NHGRI NIH HHS/United States ; R21 DC012747/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Conserved Sequence ; Drosophila melanogaster ; Evolution, Molecular ; HEK293 Cells ; Humans ; Ion Channels/classification/*genetics/*metabolism ; Membrane Proteins/classification/*genetics/*metabolism ; Mice ; Otolithic Membrane/growth & development ; Phylogeny ; Protons ; Taste Buds/*metabolism ; Tissue Distribution ; Transcriptome ; }, abstract = {Ion channels form the basis for cellular electrical signaling. Despite the scores of genetically identified ion channels selective for other monatomic ions, only one type of proton-selective ion channel has been found in eukaryotic cells. By comparative transcriptome analysis of mouse taste receptor cells, we identified Otopetrin1 (OTOP1), a protein required for development of gravity-sensing otoconia in the vestibular system, as forming a proton-selective ion channel. We found that murine OTOP1 is enriched in acid-detecting taste receptor cells and is required for their zinc-sensitive proton conductance. Two related murine genes, Otop2 and Otop3, and a Drosophila ortholog also encode proton channels. Evolutionary conservation of the gene family and its widespread tissue distribution suggest a broad role for proton channels in physiology and pathophysiology.}, } @article {pmid29371427, year = {2018}, author = {Samkharadze, N and Zheng, G and Kalhor, N and Brousse, D and Sammak, A and Mendes, UC and Blais, A and Scappucci, G and Vandersypen, LMK}, title = {Strong spin-photon coupling in silicon.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1123-1127}, doi = {10.1126/science.aar4054}, pmid = {29371427}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Long coherence times of single spins in silicon quantum dots make these systems highly attractive for quantum computation, but how to scale up spin qubit systems remains an open question. As a first step to address this issue, we demonstrate the strong coupling of a single electron spin and a single microwave photon. The electron spin is trapped in a silicon double quantum dot, and the microwave photon is stored in an on-chip high-impedance superconducting resonator. The electric field component of the cavity photon couples directly to the charge dipole of the electron in the double dot, and indirectly to the electron spin, through a strong local magnetic field gradient from a nearby micromagnet. Our results provide a route to realizing large networks of quantum dot-based spin qubit registers.}, } @article {pmid29371426, year = {2018}, author = {Gu, B and Swigut, T and Spencley, A and Bauer, MR and Chung, M and Meyer, T and Wysocka, J}, title = {Transcription-coupled changes in nuclear mobility of mammalian cis-regulatory elements.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1050-1055}, doi = {10.1126/science.aao3136}, pmid = {29371426}, issn = {1095-9203}, support = {P50 GM107615/GM/NIGMS NIH HHS/United States ; T32 CA009302/CA/NCI NIH HHS/United States ; R01 GM112720/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Bacterial Proteins ; CRISPR-Associated Protein 9 ; Cell Line ; Cell Nucleus/genetics ; Endonucleases ; Mice ; Oligonucleotide Array Sequence Analysis ; RNA Polymerase II/metabolism ; RNA, Guide/*genetics ; *Regulatory Sequences, Nucleic Acid ; Single Molecule Imaging/*methods ; Single-Cell Analysis/*methods ; *Transcription, Genetic ; Transcriptional Activation ; }, abstract = {To achieve guide RNA (gRNA) multiplexing and an efficient delivery of tens of distinct gRNAs into single cells, we developed a molecular assembly strategy termed chimeric array of gRNA oligonucleotides (CARGO). We coupled CARGO with dCas9 (catalytically dead Cas9) imaging to quantitatively measure the movement of enhancers and promoters that undergo differentiation-associated activity changes in live embryonic stem cells. Whereas all examined functional elements exhibited subdiffusive behavior, their relative mobility increased concurrently with transcriptional activation. Furthermore, acute perturbation of RNA polymerase II activity can reverse these activity-linked increases in loci mobility. Through quantitative CARGO-dCas9 imaging, we provide direct measurements of cis-regulatory element dynamics in living cells and distinct cellular and activity states and uncover an intrinsic connection between cis-regulatory element mobility and transcription.}, } @article {pmid29371425, year = {2018}, author = {Lescroart, F and Wang, X and Lin, X and Swedlund, B and Gargouri, S and Sànchez-Dànes, A and Moignard, V and Dubois, C and Paulissen, C and Kinston, S and Göttgens, B and Blanpain, C}, title = {Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6380}, pages = {1177-1181}, doi = {10.1126/science.aao4174}, pmid = {29371425}, issn = {1095-9203}, support = {MR/M008975/1//Medical Research Council/United Kingdom ; R24 DK106766/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Cell Division ; Cell Lineage/genetics ; Gene Expression Regulation, Developmental ; Heart/*embryology ; Hematopoietic Stem Cells/cytology/metabolism ; Mesoderm/cytology ; Mice ; Mice, Mutant Strains ; RNA/genetics ; Sequence Analysis, RNA ; Stem Cells/*cytology/metabolism ; }, abstract = {Mouse heart development arises from Mesp1-expressing cardiovascular progenitors (CPs) that are specified during gastrulation. The molecular processes that control early regional and lineage segregation of CPs have been unclear. We performed single-cell RNA sequencing of wild-type and Mesp1-null CPs in mice. We showed that populations of Mesp1 CPs are molecularly distinct and span the continuum between epiblast and later mesodermal cells, including hematopoietic progenitors. Single-cell transcriptome analysis of Mesp1-deficient CPs showed that Mesp1 is required for the exit from the pluripotent state and the induction of the cardiovascular gene expression program. We identified distinct populations of Mesp1 CPs that correspond to progenitors committed to different cell lineages and regions of the heart, identifying the molecular features associated with early lineage restriction and regional segregation of the heart at the early stage of mouse gastrulation.}, } @article {pmid29371424, year = {2018}, author = {Doron, S and Melamed, S and Ofir, G and Leavitt, A and Lopatina, A and Keren, M and Amitai, G and Sorek, R}, title = {Systematic discovery of antiphage defense systems in the microbial pangenome.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {}, doi = {10.1126/science.aar4120}, pmid = {29371424}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Bacillus subtilis/genetics/*immunology/*virology ; Bacteriophages/*immunology/*pathogenicity ; Escherichia coli/genetics/*immunology/*virology ; Genes, Bacterial/*physiology ; Genome, Bacterial ; Multigene Family ; }, abstract = {The arms race between bacteria and phages led to the development of sophisticated antiphage defense systems, including CRISPR-Cas and restriction-modification systems. Evidence suggests that known and unknown defense systems are located in "defense islands" in microbial genomes. Here, we comprehensively characterized the bacterial defensive arsenal by examining gene families that are clustered next to known defense genes in prokaryotic genomes. Candidate defense systems were systematically engineered and validated in model bacteria for their antiphage activities. We report nine previously unknown antiphage systems and one antiplasmid system that are widespread in microbes and strongly protect against foreign invaders. These include systems that adopted components of the bacterial flagella and condensin complexes. Our data also suggest a common, ancient ancestry of innate immunity components shared between animals, plants, and bacteria.}, } @article {pmid29371032, year = {2018}, author = {McGovern, M and Castaneda, PG and Pekar, O and Vallier, LG and Cram, EJ and Hubbard, EJA}, title = {The DSL ligand APX-1 is required for normal ovulation in C. elegans.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {162-169}, pmid = {29371032}, issn = {1095-564X}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 GM061706/GM/NIGMS NIH HHS/United States ; R01 GM110268/GM/NIGMS NIH HHS/United States ; }, mesh = {Animal Structures/abnormalities/physiology ; Animals ; Caenorhabditis elegans/*genetics/physiology ; Caenorhabditis elegans Proteins/genetics/*physiology ; Calcium Signaling ; Endoreduplication/*genetics ; Hermaphroditic Organisms/*genetics/physiology ; Membrane Proteins/physiology ; Mitosis ; Oocytes ; Ovulation/*genetics/physiology ; Phenotype ; Receptors, Notch/deficiency/physiology ; Sodium Channels/deficiency/genetics/*physiology ; }, abstract = {DSL ligands activate the Notch receptor in many cellular contexts across metazoa to specify cell fate. In addition, Notch receptor activity is implicated in post-mitotic morphogenesis and neuronal function. In C. elegans, the DSL family ligand APX-1 is expressed in a subset of cells of the proximal gonad lineage, where it can act as a latent proliferation-promoting signal to maintain proximal germline tumors. Here we examine apx-1 in the proximal gonad and uncover a role in the maintenance of normal ovulation. Depletion of apx-1 causes an endomitotic oocyte (Emo) phenotype and ovulation defects. We find that lag-2 can substitute for apx-1 in this role, that the ovulation defect is partially suppressed by loss of ipp-5, and that lin-12 depletion causes a similar phenotype. In addition, we find that the ovulation defects are often accompanied by a delay of spermathecal distal neck closure after oocyte entry. Although calcium oscillations occur in the spermatheca, calcium signals are abnormal when the distal neck does not close completely. Moreover, oocytes sometimes cannot properly transit through the spermatheca, leading to fragmentation of oocytes once the neck closes. Finally, abnormal oocytes and neck closure defects are seen occasionally when apx-1 or lin-12 activity is reduced in adult animals, suggesting a possible post-developmental role for APX-1 and LIN-12 signaling in ovulation.}, } @article {pmid29371027, year = {2018}, author = {Machado, AFP and Rønsted, N and Bruun-Lund, S and Pereira, RAS and Paganucci de Queiroz, L}, title = {Atlantic forests to the all Americas: Biogeographical history and divergence times of Neotropical Ficus (Moraceae).}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {46-58}, doi = {10.1016/j.ympev.2018.01.015}, pmid = {29371027}, issn = {1095-9513}, mesh = {Americas ; Animals ; Bayes Theorem ; Biodiversity ; Ficus/*classification ; Forests ; Phylogeny ; Phylogeography ; }, abstract = {Ficus (Moraceae) is well diversified in the Neotropics with two lineages inhabiting the wet forests of this region. The hemiepiphytes of section Americanae are the most diversified with c. 120 species, whereas section Pharmacosycea includes about 20 species mostly with a terrestrial habit. To reconstruct the biogeographical history and diversification of Ficus in the Americas, we produced a dated Bayesian phylogenetic hypothesis of Neotropical Ficus including two thirds of the species sequenced for five nuclear regions (At103, ETS, G3pdh, ITS/5.8S and Tpi). Ancestral range was estimated using all models available in Biogeobears and Binary State Speciation and Extinction analysis was used to evaluate the role of the initial habit and propagule size in diversification. The phylogenetic analyses resolved both Neotropical sections as monophyletic but the internal relationships between species in section Americanae remain unclear. Ficus started their diversification in the Neotropics between the Oligocene and Miocene. The genus experienced two bursts of diversification: in the middle Miocene and the Pliocene. Colonization events from the Amazon to adjacent areas coincide with the end of the Pebas system (10 Mya) and the connection of landmasses. Divergence of endemic species in the Atlantic forest is inferred to have happened after its isolation and the opening and consolidation of the Cerrado. Our results suggest a complex diversification in the Atlantic forest differing between postulated refuges and more instable areas in the South distribution of the forest. Finally the selection for initial hemiepiphytic habit and small to medium propagule size influenced the diversification and current distribution of the species at Neotropical forests marked by the historical instability and long-distance dispersal.}, } @article {pmid29370947, year = {2018}, author = {Vilas, CK and Emery, LE and Denchi, EL and Miller, KM}, title = {Caught with One's Zinc Fingers in the Genome Integrity Cookie Jar.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {313-325}, pmid = {29370947}, issn = {0168-9525}, support = {R01 CA198279/CA/NCI NIH HHS/United States ; R01 CA201268/CA/NCI NIH HHS/United States ; R01 GM122987/GM/NIGMS NIH HHS/United States ; }, mesh = {Aging/*genetics/metabolism ; DNA/genetics/metabolism ; DNA Breaks, Double-Stranded ; *DNA Repair ; DNA-Binding Proteins/classification/*genetics/metabolism ; Genome, Human ; Genomic Instability ; Histones/genetics/metabolism ; Humans ; Neoplasms/*genetics/metabolism/pathology ; Protein Binding ; *Protein Processing, Post-Translational ; RNA/genetics/metabolism ; *Telomere Homeostasis ; Zinc Fingers/*genetics ; }, abstract = {Zinc finger (ZnF) domains are present in at least 5% of human proteins. First characterized as binding to DNA, ZnFs display extraordinary binding plasticity and can bind to RNA, lipids, proteins, and protein post-translational modifications (PTMs). The diverse binding properties of ZnFs have made their functional characterization challenging. While once confined to large and poorly characterized protein families, proteomic, cellular, and molecular studies have begun to shed light on their involvement as protectors of the genome. We focus here on the emergent roles of ZnF domain-containing proteins in promoting genome integrity, including their involvement in telomere maintenance and DNA repair. These findings have highlighted the need for further characterization of ZnF proteins, which can reveal the functions of this large gene class in normal cell function and human diseases, including those involving genome instability such as aging and cancer.}, } @article {pmid29370866, year = {2018}, author = {Dishon, N and Oldmeadow, JA and Kaufman, J}, title = {Trait self-awareness predicts perceptions of choice meaningfulness in a decision-making task.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {75}, pmid = {29370866}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Choice Behavior/*physiology ; Decision Making/*physiology ; Feedback, Psychological/physiology ; Female ; Humans ; Male ; Middle Aged ; Perception/*physiology ; Personality Inventory ; *Self Concept ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: Seminal theorists such as Erikson, Bruner, Frankl and Rogers have underscored the importance of meaning in psychological life. However contemporary scholars interested in meaning have noted that further investigation of the individual differences associated with meaning-making is still needed. In the present study we explored whether individual differences in trait self-awareness were associated with perceptions of choice meaningfulness in a decision-making task.

RESULTS: All participants engaged in a decision-making task wherein they were asked to choose their preferred painting out of pairs of sequentially presented abstract paintings. Participants in the experimental condition were provided with feedback that their choices had been diagnostic of important personality characteristics whereas those in the control condition were not. All participants were then prompted to reflect on their choices before rating the subjective meaningfulness that they associated with their choices and completing measures to assess trait self-awareness. As anticipated, persons with higher levels of trait self-awareness tended to seek out and find more meaning compared to those lower in trait self-awareness. However contrary to expectations, feedback about the self-relevance of choices did not moderate perceptions of choice meaningfulness. Implications of these findings as well as directions for future research are also discussed.}, } @article {pmid29370828, year = {2018}, author = {Marami, D and Hailu, K and Tolera, M}, title = {Prevalence and antimicrobial susceptibility pattern of Salmonella and Shigella species among asymptomatic food handlers working in Haramaya University cafeterias, Eastern Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {74}, pmid = {29370828}, issn = {1756-0500}, mesh = {Adult ; Anti-Infective Agents/*pharmacology ; Cross-Sectional Studies ; Dysentery, Bacillary/epidemiology/microbiology ; Ethiopia/epidemiology ; Feces/microbiology ; Female ; *Food Handling ; Food Services ; Humans ; Hygiene/standards ; Male ; Microbial Sensitivity Tests ; Prevalence ; Salmonella/*drug effects/physiology ; Salmonella Infections/epidemiology/microbiology ; Shigella/*drug effects/physiology ; Universities ; }, abstract = {OBJECTIVE: Salmonellosis and Shigellosis remain a major public health problem across the globe, particularly in developing countries like Ethiopia, where hand hygiene and food microbiology are still below the required standards. The growing problem of antimicrobial resistance species also continues to pose public health challenges. This study assessed the prevalence and antimicrobial susceptibility pattern of Salmonella and Shigella species among asymptomatic food handlers. A cross-sectional study was conducted among 417 randomly selected asymptomatic food handlers. Data were collected using a structured questionnaire. The stool specimens collected were examined for Salmonella and Shigella species using standard bacteriological methods. Descriptive statistics were used to describe the basic features of the data.

RESULTS: The overall prevalence of Salmonella and Shigella species was 5.04%. Salmonella and Shigella species were 76.2% resistant to both co-trimoxazole and tetracycline, 71.4% to amoxicillin and 66.7% to chloramphenicol. Moreover, 85.7% of Salmonella and Shigella species were multidrug resistant. The findings highlighted the food handlers as potential sources of food borne infections, which demands the establishment of appropriate hygiene and sanitary control measures at the University cafeterias.}, } @article {pmid29370802, year = {2018}, author = {Julca, I and Marcet-Houben, M and Vargas, P and Gabaldón, T}, title = {Phylogenomics of the olive tree (Olea europaea) reveals the relative contribution of ancient allo- and autopolyploidization events.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {15}, pmid = {29370802}, issn = {1741-7007}, abstract = {BACKGROUND: Polyploidization is one of the major evolutionary processes that shape eukaryotic genomes, being particularly common in plants. Polyploids can arise through direct genome doubling within a species (autopolyploidization) or through the merging of genomes from distinct species after hybridization (allopolyploidization). The relative contribution of both mechanisms in plant evolution is debated. Here we used phylogenomics to dissect the tempo and mode of duplications in the genome of the olive tree (Olea europaea), one of the first domesticated Mediterranean fruit trees.

RESULTS: Our results depict a complex scenario involving at least three past polyploidization events, of which two-at the bases of the family Oleaceae and the tribe Oleeae, respectively-are likely to be the result of ancient allopolyploidization. A more recent polyploidization involves specifically the olive tree and relatives.

CONCLUSION: Our results show the power of phylogenomics to distinguish between allo- and auto polyploidization events and clarify the contributions of duplications in the evolutionary history of the olive tree.}, } @article {pmid29370772, year = {2018}, author = {Boschiero, C and Moreira, GCM and Gheyas, AA and Godoy, TF and Gasparin, G and Mariani, PDSC and Paduan, M and Cesar, ASM and Ledur, MC and Coutinho, LL}, title = {Genome-wide characterization of genetic variants and putative regions under selection in meat and egg-type chicken lines.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {83}, pmid = {29370772}, issn = {1471-2164}, support = {2014/08704-0//Fundação de Amparo à Pesquisa do Estado de São Paulo (BR)/International ; 370620/2013-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; 14/21380-9//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 15/00616-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; }, mesh = {Animals ; Avian Proteins/*genetics ; Brazil ; Chickens/*classification/*genetics ; Eggs ; Genome ; Genomics ; High-Throughput Nucleotide Sequencing ; INDEL Mutation ; Meat/*analysis ; Phenotype ; *Polymorphism, Single Nucleotide ; Quantitative Trait Loci ; *Selection, Genetic ; }, abstract = {BACKGROUND: Meat and egg-type chickens have been selected for several generations for different traits. Artificial and natural selection for different phenotypes can change frequency of genetic variants, leaving particular genomic footprints throghtout the genome. Thus, the aims of this study were to sequence 28 chickens from two Brazilian lines (meat and white egg-type) and use this information to characterize genome-wide genetic variations, identify putative regions under selection using Fst method, and find putative pathways under selection.

RESULTS: A total of 13.93 million SNPs and 1.36 million INDELs were identified, with more variants detected from the broiler (meat-type) line. Although most were located in non-coding regions, we identified 7255 intolerant non-synonymous SNPs, 512 stopgain/loss SNPs, 1381 frameshift and 1094 non-frameshift INDELs that may alter protein functions. Genes harboring intolerant non-synonymous SNPs affected metabolic pathways related mainly to reproduction and endocrine systems in the white-egg layer line, and lipid metabolism and metabolic diseases in the broiler line. Fst analysis in sliding windows, using SNPs and INDELs separately, identified over 300 putative regions of selection overlapping with more than 250 genes. For the first time in chicken, INDEL variants were considered for selection signature analysis, showing high level of correlation in results between SNP and INDEL data. The putative regions of selection signatures revealed interesting candidate genes and pathways related to important phenotypic traits in chicken, such as lipid metabolism, growth, reproduction, and cardiac development.

CONCLUSIONS: In this study, Fst method was applied to identify high confidence putative regions under selection, providing novel insights into selection footprints that can help elucidate the functional mechanisms underlying different phenotypic traits relevant to meat and egg-type chicken lines. In addition, we generated a large catalog of line-specific and common genetic variants from a Brazilian broiler and a white egg layer line that can be used for genomic studies involving association analysis with phenotypes of economic interest to the poultry industry.}, } @article {pmid29370763, year = {2018}, author = {Brinton, J and Simmonds, J and Uauy, C}, title = {Ubiquitin-related genes are differentially expressed in isogenic lines contrasting for pericarp cell size and grain weight in hexaploid wheat.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {22}, pmid = {29370763}, issn = {1471-2229}, support = {BBS/E/J/000C0628//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P013511/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/P016855/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; IWYP76//International Wheat Yield Partnership/International ; }, mesh = {Edible Grain/*growth & development/metabolism ; Plant Proteins/*genetics/metabolism ; Polyploidy ; *Quantitative Trait Loci ; Sequence Analysis, RNA ; Triticum/*genetics/*growth & development ; Ubiquitins/*genetics/metabolism ; }, abstract = {BACKGROUND: There is an urgent need to increase global crop production. Identifying and combining specific genes controlling distinct biological processes holds the potential to enhance crop yields. Transcriptomics is a powerful tool to gain insights into the complex gene regulatory networks that underlie such traits, but relies on the availability of a high-quality reference sequence and accurate gene models. Previously, we identified a grain weight QTL on wheat chromosome 5A (5A QTL) which acts during early grain development to increase grain length through cell expansion in the pericarp. In this study, we performed RNA-sequencing on near isogenic lines (NILs) segregating for the 5A QTL and used the latest gene models to identify differentially regulated genes and pathways that potentially influence pericarp cell size and grain weight in wheat.

RESULTS: We sampled grains at 4 and 8 days post anthesis and found that genes associated with metabolism, biosynthesis, proteolysis and the defence response are upregulated during this stage of grain development in both NILs. We identified a specific set of 112 transcripts differentially expressed (DE) between 5A NILs at either time point, including eight potential candidates for the causal 5A gene and its downstream targets. The 112 DE transcripts had functional annotations including non-coding RNA, transposon-associated, cell-cycle control, ubiquitin-related, heat-shock, transcription and histone-related. Many of the genes identified belong to families that have been previously associated with seed/grain development in other species. Notably, we identified DE transcripts at almost all steps of the pathway associated with ubiquitin-mediated protein degradation. In the promoters of a subset of DE transcripts we identified enrichment of binding sites associated with C2H2, MYB/SANT, YABBY, AT-HOOK and Trihelix transcription factor families.

CONCLUSIONS: In this study, we identified DE transcripts with a diverse range of predicted biological functions, reflecting the complex nature of the pathways that control early grain development. Few of these are the direct orthologues of grain size genes in other species and none have been previously characterised in wheat. Further functional characterisation of these candidates and how they interact will provide novel insights into the control of grain size in cereals.}, } @article {pmid29370760, year = {2018}, author = {Zampieri, G and Tran, DV and Donini, M and Navarin, N and Aiolli, F and Sperduti, A and Valle, G}, title = {Scuba: scalable kernel-based gene prioritization.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {23}, pmid = {29370760}, issn = {1471-2105}, support = {Bioinfogen Strategic Project//Università degli Studi di Padova/International ; }, mesh = {Algorithms ; Databases, Factual ; Genome-Wide Association Study ; Humans ; Internet ; *User-Computer Interface ; }, abstract = {BACKGROUND: The uncovering of genes linked to human diseases is a pressing challenge in molecular biology and precision medicine. This task is often hindered by the large number of candidate genes and by the heterogeneity of the available information. Computational methods for the prioritization of candidate genes can help to cope with these problems. In particular, kernel-based methods are a powerful resource for the integration of heterogeneous biological knowledge, however, their practical implementation is often precluded by their limited scalability.

RESULTS: We propose Scuba, a scalable kernel-based method for gene prioritization. It implements a novel multiple kernel learning approach, based on a semi-supervised perspective and on the optimization of the margin distribution. Scuba is optimized to cope with strongly unbalanced settings where known disease genes are few and large scale predictions are required. Importantly, it is able to efficiently deal both with a large amount of candidate genes and with an arbitrary number of data sources. As a direct consequence of scalability, Scuba integrates also a new efficient strategy to select optimal kernel parameters for each data source. We performed cross-validation experiments and simulated a realistic usage setting, showing that Scuba outperforms a wide range of state-of-the-art methods.

CONCLUSIONS: Scuba achieves state-of-the-art performance and has enhanced scalability compared to existing kernel-based approaches for genomic data. This method can be useful to prioritize candidate genes, particularly when their number is large or when input data is highly heterogeneous. The code is freely available at https://github.com/gzampieri/Scuba .}, } @article {pmid29370759, year = {2018}, author = {Deng, F and Zhang, X and Wang, W and Yuan, R and Shen, F}, title = {Identification of Gossypium hirsutum long non-coding RNAs (lncRNAs) under salt stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {23}, pmid = {29370759}, issn = {1471-2229}, support = {2015zx08005-002//China Major Projects for Transgenic Breeding/International ; }, mesh = {Gossypium/genetics/*physiology ; RNA, Long Noncoding/*genetics/metabolism ; RNA, Plant/*genetics/metabolism ; Real-Time Polymerase Chain Reaction ; *Stress, Physiological ; }, abstract = {BACKGROUND: Long non-coding RNAs (lncRNAs) represent a class of riboregulators that either directly act in long form or are processed into shorter microRNAs (miRNAs) and small interfering RNAs. Long noncoding RNAs (lncRNAs) are arbitrarily defined as RNA genes larger than 200 nt in length that have no apparent coding potential. lncRNAs have emerged as playing important roles in various biological regulatory processes and are expressed in a more tissue-specific manner than mRNA. Emerging evidence shows that lncRNAs participate in stress-responsive regulation.

RESULTS: In this study, in order to develop a comprehensive catalogue of lncRNAs in upland cotton under salt stress, we performed whole-transcriptome strand-specific RNA sequencing for three-leaf stage cotton seedlings treated with salt stress (S_NaCl) and controls (S_CK). In total we identified 1117 unique lncRNAs in this study and 44 differentially expressed RNAs were identified as potential non-coding RNAs. For the differentially expressed lncRNAs that were identified as intergenic lncRNAs (lincRNA), we analysed the gene ontology enrichment of cis targets and found that cis target protein-coding genes were mainly enriched in stress-related categories. Real-time quantitative PCR confirmed that all selected lincRNAs responsive to salt stress. We found lnc_388 was likely as regulator of Gh_A09G1182. And lnc_883 may participate in regulating tolerance to salt stress by modulating the expression of Gh_D03G0339 MS_channel. We then predicted the target mimics for miRNA in Gossypium. six miRNAs were identified, and the result of RT-qPCR with lncRNA and miRNA suggested that lnc_973 and lnc_253 may regulate the expression of ghr-miR399 and ghr-156e as a target mimic under salt stress.

CONCLUSIONS: We identified 44 lincRNAs that were differentially expressed under salt stress. These lincRNAs may target protein-coding genes via cis-acting regulation. We also discovered that specifically-expressed lincRNAs under salt stress may act as endogenous target mimics for conserved miRNAs. These findings extend the current view on lincRNAs as ubiquitous regulators under stress stress.}, } @article {pmid29370758, year = {2018}, author = {Wittchen, M and Busche, T and Gaspar, AH and Lee, JH and Ton-That, H and Kalinowski, J and Tauch, A}, title = {Transcriptome sequencing of the human pathogen Corynebacterium diphtheriae NCTC 13129 provides detailed insights into its transcriptional landscape and into DtxR-mediated transcriptional regulation.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {82}, pmid = {29370758}, issn = {1471-2164}, support = {R01 DE017382/DE/NIDCR NIH HHS/United States ; R01 DE025015/DE/NIDCR NIH HHS/United States ; DE025015/NH/NIH HHS/United States ; DE017382/NH/NIH HHS/United States ; }, mesh = {Bacterial Proteins/antagonists & inhibitors/*genetics/metabolism ; Corynebacterium diphtheriae/*genetics/isolation & purification ; DNA-Binding Proteins/antagonists & inhibitors/*genetics/metabolism ; Diphtheria/*microbiology ; Diphtheria Toxin/metabolism ; *Gene Expression Regulation, Bacterial ; Genetic Variation ; Genome, Bacterial ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Iron/metabolism ; Operon ; Promoter Regions, Genetic ; Transcriptome ; }, abstract = {BACKGROUND: The human pathogen Corynebacterium diphtheriae is the causative agent of diphtheria. In the 1990s a large diphtheria outbreak in Eastern Europe was caused by the strain C. diphtheriae NCTC 13129. Although the genome was sequenced more than a decade ago, not much is known about its transcriptome. Our aim was to use transcriptome sequencing (RNA-Seq) to close this knowledge gap and gain insights into the transcriptional landscape of a C. diphtheriae tox+ strain.

RESULTS: We applied two different RNA-Seq techniques, one to retrieve 5'-ends of primary transcripts and the other to characterize the whole transcriptional landscape in order to gain insights into various features of the C. diphtheriae NCTC 13129 transcriptome. By examining the data we identified 1656 transcription start sites (TSS), of which 1202 were assigned to genes and 454 to putative novel transcripts. By using the TSS data promoter regions recognized by the housekeeping sigma factor σA and its motifs were analyzed in detail, revealing a well conserved -10 but an only weakly conserved -35 motif, respectively. Furthermore, with the TSS data 5'-UTR lengths were explored. The observed 5'-UTRs range from zero length (leaderless transcripts), which make up 20% of all genes, up to over 450 nt long leaders, which may harbor regulatory functions. The C. diphtheriae transcriptome consists of 471 operons which are further divided into 167 sub-operon structures. In a differential expression analysis approach, we discovered that genetic disruption of the iron-sensing transcription regulator DtxR, which controls expression of diphtheria toxin (DT), causes a strong influence on general gene expression. Nearly 15% of the genome is differentially transcribed, indicating that DtxR might have other regulatory functions in addition to regulation of iron metabolism and DT. Furthermore, our findings shed light on the transcriptional landscape of the DT encoding gene tox and present evidence for two tox antisense RNAs, which point to a new way of transcriptional regulation of toxin production.

CONCLUSIONS: This study presents extensive insights into the transcriptome of C. diphtheriae and provides a basis for future studies regarding gene characterization, transcriptional regulatory networks, and regulation of the tox gene in particular.}, } @article {pmid29370757, year = {2018}, author = {Hamza, R and Pérez-Hedo, M and Urbaneja, A and Rambla, JL and Granell, A and Gaddour, K and Beltrán, JP and Cañas, LA}, title = {Expression of two barley proteinase inhibitors in tomato promotes endogenous defensive response and enhances resistance to Tuta absoluta.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {24}, pmid = {29370757}, issn = {1471-2229}, support = {BIO2013-40747-R//Ministerio de Economía y Competitividad/International ; AGL2014-55616-C3//Ministerio de Economía y Competitividad/International ; }, mesh = {Animals ; Antibiosis/*genetics ; Cysteine Proteinase Inhibitors/metabolism ; Hordeum/*genetics ; Larva/growth & development/physiology ; Lycopersicon esculentum/genetics/*physiology ; Moths/growth & development/*physiology ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified/genetics/physiology ; *Protease Inhibitors/metabolism ; Serine Proteinase Inhibitors/genetics/metabolism ; }, abstract = {BACKGROUND: Plants and insects have coexisted for million years and evolved a set of interactions which affect both organisms at different levels. Plants have developed various morphological and biochemical adaptations to cope with herbivores attacks. However, Tuta absoluta (Meyrick) (Lepidoptera: Gelechiidae) has become the major pest threatening tomato crops worldwide and without the appropriated management it can cause production losses between 80 to 100%.

RESULTS: The aim of this study was to investigate the in vivo effect of a serine proteinase inhibitor (BTI-CMe) and a cysteine proteinase inhibitor (Hv-CPI2) from barley on this insect and to examine the effect their expression has on tomato defensive responses. We found that larvae fed on tomato transgenic plants co-expressing both proteinase inhibitors showed a notable reduction in weight. Moreover, only 56% of these larvae reached the adult stage. The emerged adults showed wings deformities and reduced fertility. We also investigated the effect of proteinase inhibitors ingestion on the insect digestive enzymes. Our results showed a decrease in larval trypsin activity. Transgenes expression had no harmful effect on Nesidiocoris tenuis (Reuter) (Heteroptera: Miridae), a predator of Tuta absoluta, despite transgenic tomato plants attracted the mirid. We also found that barley cystatin expression promoted plant defense by inducing the expression of the tomato endogenous wound inducible Proteinase inhibitor 2 (Pin2) gene, increasing the production of glandular trichomes and altering the emission of volatile organic compounds.

CONCLUSION: Our results demonstrate the usefulness of the co-expression of different proteinase inhibitors for the enhancement of plant resistance to Tuta absoluta.}, } @article {pmid29370753, year = {2018}, author = {Zhao, X and Luo, L and Cao, Y and Liu, Y and Li, Y and Wu, W and Lan, Y and Jiang, Y and Gao, S and Zhang, Z and Shen, Y and Pan, G and Lin, H}, title = {Genome-wide association analysis and QTL mapping reveal the genetic control of cadmium accumulation in maize leaf.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {91}, pmid = {29370753}, issn = {1471-2164}, support = {31471513//National Natural Science Foundation of China/International ; 31601236//National Natural Science Foundation of China/International ; }, mesh = {Cadmium/*metabolism ; Chromosome Mapping ; Chromosomes, Plant ; *Gene Expression Regulation, Plant ; Genetic Markers ; *Genome-Wide Association Study ; Genotype ; Phenotype ; Plant Leaves/*genetics/metabolism ; Plant Proteins/genetics ; *Quantitative Trait Loci ; Zea mays/*genetics/metabolism ; }, abstract = {BACKGROUND: Accumulation of cadmium (Cd) in maize (Zea mays L.) poses a significant risk to human health as it is ingested via the food chain. A genome-wide association study (GWAS) was conducted in a population of 269 maize accessions with 43,737 single nucleotide polymorphisms (SNPs) to identify candidate genes and favorable alleles for controlling Cd accumulation in maize.

RESULTS: When grown in contaminated soil, accessions varied significantly in leaf Cd concentration at both the seeding and maturing stages with phenotypic variation and the coefficient of variation all above 48%. The co-localized region between SYN27837 (147,034,650 bp) and SYN36598 (168,551,327 bp) on chromosome 2 was associated with leaf Cd under three soil conditions varying in Cd content in 2015 and 2016. The significant SNP (SYN25051) at position 161,275,547 could explained 27.1% of the phenotype variation. Through QTL mapping using the IBMSyn10 double haploid (DH) population, we validated the existence of a major QTL identified by GWAS; qLCd2 could explain the 39.8% average phenotype variation across the experiments. Expression of GRMZM2G175576 encoding a cadmium/zinc-transporting ATPase underlying the QTL was significantly increased in roots, stems and leaves of B73, a low Cd accumulation line in response to Cd stress.

CONCLUSIONS: Our findings provide new insights into the genetic control of Cd accumulation and could aid rapid development of maize genotypes with low-Cd accumulation by manipulation of the favorable alleles.}, } @article {pmid29370752, year = {2018}, author = {Ando, T and Fujiwara, H and Kojima, T}, title = {The pivotal role of aristaless in development and evolution of diverse antennal morphologies in moths and butterflies.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {8}, pmid = {29370752}, issn = {1471-2148}, support = {08J08820//Japan Society for the Promotion of Science/International ; 20570198//Japan Society for the Promotion of Science/International ; 24570230//Japan Society for the Promotion of Science/International ; 20017007//Ministry of Education, Culture, Sports, Science and Technology/International ; 22128005//Ministry of Education, Culture, Sports, Science and Technology/International ; 15H05778//Ministry of Education, Culture, Sports, Science and Technology/International ; }, mesh = {Animals ; Arthropod Antennae/*anatomy & histology ; *Biological Evolution ; Body Patterning/genetics ; Bombyx/anatomy & histology/genetics ; Butterflies/*anatomy & histology/*embryology/genetics ; Female ; Gene Expression Regulation, Developmental ; *Genes, Homeobox ; Male ; Metamorphosis, Biological/genetics ; Moths/*anatomy & histology/*embryology/genetics ; Receptors, Notch/metabolism ; Signal Transduction/genetics ; Wnt Proteins/metabolism ; }, abstract = {BACKGROUND: Antennae are multi-segmented appendages and main odor-sensing organs in insects. In Lepidoptera (moths and butterflies), antennal morphologies have diversified according to their ecological requirements. While diurnal butterflies have simple, rod-shaped antennae, nocturnal moths have antennae with protrusions or lateral branches on each antennal segment for high-sensitive pheromone detection. A previous study on the Bombyx mori (silk moth) antenna, forming two lateral branches per segment, during metamorphosis has revealed the dramatic change in expression of antennal patterning genes to segmentally reiterated, branch-associated pattern and abundant proliferation of cells contributing almost all the dorsal half of the lateral branch. Thus, localized cell proliferation possibly controlled by the branch-associated expression of antennal patterning genes is implicated in lateral branch formation. Yet, actual gene function in lateral branch formation in Bombyx mori and evolutionary mechanism of various antennal morphologies in Lepidoptera remain elusive.

RESULTS: We investigated the function of several genes and signaling specifically in lateral branch formation in Bombyx mori by the electroporation-mediated incorporation of siRNAs or morpholino oligomers. Knock down of aristaless, a homeobox gene expressed specifically in the region of abundant cell proliferation within each antennal segment, during metamorphosis resulted in missing or substantial shortening of lateral branches, indicating its importance for lateral branch formation. aristaless expression during metamorphosis was lost by knock down of Distal-less and WNT signaling but derepressed by knock down of Notch signaling, suggesting the strict determination of the aristaless expression domain within each antennal segment by the combinatorial action of them. In addition, analyses of pupal aristaless expression in antennae with various morphologies of several lepidopteran species revealed that the aristaless expression pattern has a striking correlation with antennal shapes, whereas the segmentally reiterated expression pattern was observed irrespective of antennal morphologies.

CONCLUSIONS: Our results presented here indicate the significance of aristaless function in lateral branch formation in B. mori and imply that the diversification in the aristaless expression pattern within each antennal segment during metamorphosis is one of the significant determinants of antennal morphologies. According to these findings, we propose a mechanism underlying development and evolution of lepidopteran antennae with various morphologies.}, } @article {pmid29370751, year = {2018}, author = {Han, Z and Zhang, J and Cai, S and Chen, X and Quan, X and Zhang, G}, title = {Association mapping for total polyphenol content, total flavonoid content and antioxidant activity in barley.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {81}, pmid = {29370751}, issn = {1471-2164}, support = {31620103912, 31471480, and 31401369//National Natural Science Foundation of China/International ; }, mesh = {Antioxidants/*metabolism ; Flavonoids/*metabolism ; *Genetic Markers ; Genome-Wide Association Study ; Genotype ; Hordeum/*genetics/growth & development/metabolism ; Phylogeny ; Plant Proteins/*genetics ; Polymorphism, Genetic ; Polyphenols/*metabolism ; *Quantitative Trait Loci ; }, abstract = {BACKGROUND: The interest has been increasing on the phenolic compounds in plants because of their nutritive function as food and the roles regulating plant growth. However, their underlying genetic mechanism in barley is still not clear.

RESULTS: A genome-wide association study (GWAS) was conducted for total phenolic content (TPC), total flavonoid content (FLC) and antioxidant activity (AOA) in 67 cultivated and 156 Tibetan wild barley genotypes. Most markers associated with phenolic content were different in cultivated and wild barleys. The markers bPb-0572 and bPb-4531 were identified as the major QTLs controlling phenolic compounds in Tibetan wild barley. Moreover, the marker bPb-4531 was co-located with the UDP- glycosyltransferase gene (HvUGT), which is a homolog to Arabidopsis UGTs and involved in biosynthesis of flavonoid glycosides .

CONCLUSIONS: GWAS is an efficient tool for exploring the genetic architecture of phenolic compounds in the cultivated and Tibetan wild barleys. The DArT markers applied in this study can be used in barley breeding for developing new barley cultivars with higher phenolics content. The candidate gene (HvUGT) provides a potential route for deep understanding of the molecular mechanism of flavonoid synthesis.}, } @article {pmid29370750, year = {2018}, author = {Adhikari, B and Cheng, J}, title = {CONFOLD2: improved contact-driven ab initio protein structure modeling.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {22}, pmid = {29370750}, issn = {1471-2105}, support = {R01 GM093123/GM/NIGMS NIH HHS/United States ; R01GM093123/NH/NIH HHS/United States ; }, mesh = {Algorithms ; Databases, Protein ; Internet ; Protein Conformation ; Protein Folding ; Proteins/*chemistry/metabolism ; *User-Computer Interface ; }, abstract = {BACKGROUND: Contact-guided protein structure prediction methods are becoming more and more successful because of the latest advances in residue-residue contact prediction. To support contact-driven structure prediction, effective tools that can quickly build tertiary structural models of good quality from predicted contacts need to be developed.

RESULTS: We develop an improved contact-driven protein modelling method, CONFOLD2, and study how it may be effectively used for ab initio protein structure prediction with predicted contacts as input. It builds models using various subsets of input contacts to explore the fold space under the guidance of a soft square energy function, and then clusters the models to obtain the top five models. CONFOLD2 obtains an average reconstruction accuracy of 0.57 TM-score for the 150 proteins in the PSICOV contact prediction dataset. When benchmarked on the CASP11 contacts predicted using CONSIP2 and CASP12 contacts predicted using Raptor-X, CONFOLD2 achieves a mean TM-score of 0.41 on both datasets.

CONCLUSION: CONFOLD2 allows to quickly generate top five structural models for a protein sequence when its secondary structures and contacts predictions at hand. The source code of CONFOLD2 is publicly available at https://github.com/multicom-toolbox/CONFOLD2/ .}, } @article {pmid29370748, year = {2018}, author = {Yousefi, S and Abbassi-Daloii, T and Kraaijenbrink, T and Vermaat, M and Mei, H and van 't Hof, P and van Iterson, M and Zhernakova, DV and Claringbould, A and Franke, L and 't Hart, LM and Slieker, RC and van der Heijden, A and de Knijff, P and , and 't Hoen, PAC}, title = {A SNP panel for identification of DNA and RNA specimens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {90}, pmid = {29370748}, issn = {1471-2164}, support = {184.021.007//The Netherlands Organization for Scientific Research/International ; }, mesh = {DNA/*analysis/genetics ; DNA Fingerprinting ; Ethnic Groups/*genetics ; Gene Frequency ; Genetic Testing ; *Genetics, Population ; Genotype ; High-Throughput Nucleotide Sequencing ; Humans ; Individuality ; Linkage Disequilibrium ; Patient Identification Systems/*methods ; *Polymorphism, Single Nucleotide ; RNA/*analysis/genetics ; }, abstract = {BACKGROUND: SNP panels that uniquely identify an individual are useful for genetic and forensic research. Previously recommended SNP panels are based on DNA profiles and mostly contain intragenic SNPs. With the increasing interest in RNA expression profiles, we aimed for establishing a SNP panel for both DNA and RNA-based genotyping.

RESULTS: To determine a small set of SNPs with maximally discriminative power, genotype calls were obtained from DNA and blood-derived RNA sequencing data belonging to healthy, geographically dispersed, Dutch individuals. SNPs were selected based on different criteria like genotype call rate, minor allele frequency, Hardy-Weinberg equilibrium and linkage disequilibrium. A panel of 50 SNPs was sufficient to identify an individual uniquely: the probability of identity was 6.9 × 10- 20 when assuming no family relations and 1.2 × 10- 10 when accounting for the presence of full sibs. The ability of the SNP panel to uniquely identify individuals on DNA and RNA level was validated in an independent population dataset. The panel is applicable to individuals from European descent, with slightly lower power in non-Europeans. Whereas most of the genes containing the 50 SNPs are expressed in various tissues, our SNP panel needs optimization for other tissues than blood.

CONCLUSIONS: This first DNA/RNA SNP panel will be useful to identify sample mix-ups in biomedical research and for assigning DNA and RNA stains in crime scenes to unique individuals.}, } @article {pmid29368740, year = {2018}, author = {Nordling, L}, title = {Calestous Juma (1953-2017).}, journal = {Nature}, volume = {553}, number = {7689}, pages = {406}, doi = {10.1038/d41586-018-00627-z}, pmid = {29368740}, issn = {1476-4687}, } @article {pmid29368739, year = {2018}, author = {Blundell, BG}, title = {Trapped particle makes 3D images.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {408-409}, doi = {10.1038/d41586-018-00859-z}, pmid = {29368739}, issn = {1476-4687}, mesh = {Humans ; *Image Processing, Computer-Assisted ; *Imaging, Three-Dimensional ; }, } @article {pmid29368738, year = {2018}, author = {Kuro-O, M}, title = {Ageing-related receptors resolved.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {409-410}, doi = {10.1038/d41586-017-09032-4}, pmid = {29368738}, issn = {1476-4687}, mesh = {*Aging ; Humans ; }, } @article {pmid29368737, year = {2018}, author = {Walker, TR}, title = {China's ban on imported plastic waste could be a game changer.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {405}, doi = {10.1038/d41586-018-00933-6}, pmid = {29368737}, issn = {1476-4687}, mesh = {China ; Humans ; *Plastics ; }, } @article {pmid29368736, year = {2018}, author = {}, title = {Vaccine boosters.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {392}, doi = {10.1038/d41586-018-01073-7}, pmid = {29368736}, issn = {1476-4687}, } @article {pmid29368734, year = {2018}, author = {Schiermeier, Q}, title = {German scientists hope for windfall from incoming government.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {388}, doi = {10.1038/d41586-018-01026-0}, pmid = {29368734}, issn = {1476-4687}, mesh = {*Federal Government ; *Financing, Government ; Germany ; Gross Domestic Product ; *Research Support as Topic ; Science/*economics/*legislation & jurisprudence/trends ; }, } @article {pmid29368733, year = {2018}, author = {Morello, L and Reardon, S and Ledford, H}, title = {US researchers relieved as government shutdown ends.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {389}, doi = {10.1038/d41586-018-01069-3}, pmid = {29368733}, issn = {1476-4687}, mesh = {Budgets/*legislation & jurisprudence ; Emigration and Immigration/legislation & jurisprudence ; *Federal Government ; Research/economics/*legislation & jurisprudence ; Research Personnel/economics/*psychology ; Uncertainty ; United States ; }, } @article {pmid29368732, year = {2018}, author = {Powell, K}, title = {Technology to watch in 2018.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {531-534}, doi = {10.1038/d41586-018-01021-5}, pmid = {29368732}, issn = {1476-4687}, mesh = {Animals ; Antigens, Neoplasm/immunology ; Artificial Intelligence ; Biological Science Disciplines/*trends ; Biomedical Research/*trends ; Cancer Vaccines/immunology/therapeutic use ; Codon/genetics ; Columbidae/genetics/physiology ; Data Mining ; Female ; Fertility/genetics ; Genetic Code/genetics ; Humans ; Information Dissemination ; Male ; Multiprotein Complexes/genetics/metabolism ; Neoplasms/genetics/metabolism/pathology ; Organ Specificity/genetics ; Reproduction/genetics ; Stress, Psychological/genetics ; Transcriptome/genetics ; Viruses/pathogenicity ; }, } @article {pmid29368731, year = {2018}, author = {Ledford, H}, title = {The lost art of looking at plants.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {396-398}, doi = {10.1038/d41586-018-01075-5}, pmid = {29368731}, issn = {1476-4687}, mesh = {Botany/*history/*methods/trends ; Evolution, Molecular ; Flowers/anatomy & histology/genetics ; Gene Expression Regulation, Plant ; History, 18th Century ; History, 21st Century ; Imaging, Three-Dimensional ; Phylogeny ; Plant Breeding ; Plants/*anatomy & histology/classification/*genetics ; Tomography Scanners, X-Ray Computed ; }, } @article {pmid29368730, year = {2018}, author = {Xu, Z and Fang, L and Pan, D}, title = {Regulate prescription of Chinese medicines.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {405}, doi = {10.1038/d41586-018-01079-1}, pmid = {29368730}, issn = {1476-4687}, mesh = {Humans ; *Medicine, Chinese Traditional ; }, } @article {pmid29368729, year = {2018}, author = {}, title = {US ecologists earn more in government than in academia.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {537}, doi = {10.1038/d41586-018-01019-z}, pmid = {29368729}, issn = {1476-4687}, } @article {pmid29368728, year = {2018}, author = {Halperin, WP}, title = {Eighty years of superfluidity.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {413-414}, doi = {10.1038/d41586-018-00417-7}, pmid = {29368728}, issn = {1476-4687}, } @article {pmid29368727, year = {2018}, author = {}, title = {Brief US shutdown, harassment data and electric fishing.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {384-385}, doi = {10.1038/d41586-018-01072-8}, pmid = {29368727}, issn = {1476-4687}, } @article {pmid29368725, year = {2018}, author = {}, title = {Undergraduate physics labs don't improve US students' exam scores.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {537}, doi = {10.1038/d41586-018-01020-6}, pmid = {29368725}, issn = {1476-4687}, } @article {pmid29368724, year = {2018}, author = {Tollefson, J}, title = {China declared world's largest producer of scientific articles.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {390}, doi = {10.1038/d41586-018-00927-4}, pmid = {29368724}, issn = {1476-4687}, mesh = {*Authorship ; Bibliometrics ; China ; Inventions/statistics & numerical data ; Research Report/standards/*trends ; Science/economics/standards/*statistics & numerical data ; Technology Transfer ; United States ; }, } @article {pmid29368723, year = {2018}, author = {}, title = {Science has a gambling problem.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {379}, doi = {10.1038/d41586-018-01051-z}, pmid = {29368723}, issn = {1476-4687}, mesh = {Behavior, Addictive/*prevention & control/*psychology/rehabilitation ; Behavioral Research/*trends ; Female ; Gambling/*prevention & control/*psychology/rehabilitation ; Humans ; Public Health ; }, } @article {pmid29368722, year = {2018}, author = {Macias-Fauria, M}, title = {Satellite images show China going green.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {411-413}, doi = {10.1038/d41586-018-00996-5}, pmid = {29368722}, issn = {1476-4687}, mesh = {China ; Conservation of Natural Resources/*trends ; Desert Climate ; Droughts ; *Environmental Monitoring ; Forestry/*methods/*trends ; *Satellite Imagery ; Soil ; Trees/*growth & development ; }, } @article {pmid29368721, year = {2018}, author = {Munafò, MR and Davey Smith, G}, title = {Robust research needs many lines of evidence.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {399-401}, doi = {10.1038/d41586-018-01023-3}, pmid = {29368721}, issn = {1476-4687}, mesh = {Animals ; Artifacts ; Confounding Factors (Epidemiology) ; Humans ; Interdisciplinary Research ; *Reproducibility of Results ; Research/*standards ; *Research Design ; Uncertainty ; }, } @article {pmid29368720, year = {2018}, author = {Cyranoski, D}, title = {First monkeys cloned with technique that made Dolly the sheep.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {387-388}, doi = {10.1038/d41586-018-01027-z}, pmid = {29368720}, issn = {1476-4687}, mesh = {Animals ; *Cloning, Organism ; *Haplorhini ; Sheep ; }, } @article {pmid29368719, year = {2018}, author = {Barron, AR and Parker, BJ}, title = {Test proxy carbon prices as decision-making tools.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {405}, doi = {10.1038/d41586-018-01078-2}, pmid = {29368719}, issn = {1476-4687}, } @article {pmid29368718, year = {2018}, author = {Url, B}, title = {Don't attack science agencies for political gain.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {381}, doi = {10.1038/d41586-018-01071-9}, pmid = {29368718}, issn = {1476-4687}, mesh = {*European Union ; *Food Safety ; Glycine/adverse effects/analogs & derivatives ; Government Agencies/*legislation & jurisprudence/standards ; Policy Making ; *Politics ; Science/*legislation & jurisprudence/standards ; }, } @article {pmid29368717, year = {2018}, author = {Watson, T}, title = {Meet the street animals that stole scientists' hearts.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {535-537}, doi = {10.1038/d41586-018-01018-0}, pmid = {29368717}, issn = {1476-4687}, mesh = {*Animal Welfare/economics ; Animals ; Cats ; Dogs ; Expeditions ; *Love ; Pets/economics/*psychology ; Research Personnel/economics/*psychology ; Travel/economics ; }, } @article {pmid29368716, year = {2018}, author = {}, title = {Science must get ready for the next global flu crisis.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {380}, doi = {10.1038/d41586-018-01070-w}, pmid = {29368716}, issn = {1476-4687}, mesh = {*Disease Outbreaks ; Humans ; Influenza, Human/*epidemiology ; }, } @article {pmid29368715, year = {2018}, author = {Le Bot, N and Marte, B and Weiss, U}, title = {Frontiers in biology.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {417}, doi = {10.1038/d41586-018-00620-6}, pmid = {29368715}, issn = {1476-4687}, mesh = {Biology/*trends ; Biomedical Research/*trends ; Hematopoiesis ; Humans ; Lung Neoplasms/immunology/metabolism/therapy ; Organoids/growth & development ; Skin/immunology/microbiology ; }, } @article {pmid29368714, year = {2018}, author = {Gerstein, MB and Navarro, FCP}, title = {Gene names can confound most-searched listings.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {405}, doi = {10.1038/d41586-018-01077-3}, pmid = {29368714}, issn = {1476-4687}, } @article {pmid29368713, year = {2018}, author = {Callaway, E}, title = {Controversial femur could belong to ancient human relative.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {391-392}, doi = {10.1038/d41586-018-00972-z}, pmid = {29368713}, issn = {1476-4687}, mesh = {Femur/*anatomy & histology ; *Fossils ; History, Ancient ; Humans ; }, } @article {pmid29368712, year = {2018}, author = {Glikman, E}, title = {A beacon at the dawn of the Universe.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {410-411}, doi = {10.1038/d41586-018-00818-8}, pmid = {29368712}, issn = {1476-4687}, } @article {pmid29368711, year = {2018}, author = {Huang, KL}, title = {Most popular public searches on gene names.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {405}, doi = {10.1038/d41586-018-01076-4}, pmid = {29368711}, issn = {1476-4687}, mesh = {*Genes ; Humans ; Information Seeking Behavior ; *Search Engine ; }, } @article {pmid29368710, year = {2018}, author = {}, title = {Science after a year of President Trump.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {380}, doi = {10.1038/d41586-018-01001-9}, pmid = {29368710}, issn = {1476-4687}, mesh = {Budgets/legislation & jurisprudence ; Censorship, Research ; Emigration and Immigration/legislation & jurisprudence ; Environmental Policy/legislation & jurisprudence ; Islam ; *Politics ; Precision Medicine ; Science/economics/*legislation & jurisprudence/*trends ; Stem Cell Research ; United States ; Workforce ; }, } @article {pmid29368708, year = {2018}, author = {Mann, A}, title = {Bashing holes in the tale of Earth's troubled youth.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {393-395}, doi = {10.1038/d41586-018-01074-6}, pmid = {29368708}, issn = {1476-4687}, mesh = {Astronauts ; *Earth (Planet) ; Extraterrestrial Environment/chemistry ; History, Ancient ; *Minor Planets ; *Models, Theoretical ; Moon ; Origin of Life ; Radiometric Dating ; Reproducibility of Results ; Solar System ; Time Factors ; Uncertainty ; }, } @article {pmid29368706, year = {2018}, author = {Esser-Kahn, AP}, title = {Kiss-and-tell way to track cell contacts.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {414-415}, doi = {10.1038/d41586-018-00488-6}, pmid = {29368706}, issn = {1476-4687}, } @article {pmid29368705, year = {2018}, author = {Jackson, CRM and Bennett, NR and Du, Z and Cottrell, E and Fei, Y}, title = {Early episodes of high-pressure core formation preserved in plume mantle.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {491-495}, pmid = {29368705}, issn = {1476-4687}, abstract = {The decay of short-lived iodine (I) and plutonium (Pu) results in xenon (Xe) isotopic anomalies in the mantle that record Earth's earliest stages of formation. Xe isotopic anomalies have been linked to degassing during accretion, but degassing alone cannot account for the co-occurrence of Xe and tungsten (W) isotopic heterogeneity in plume-derived basalts and their long-term preservation in the mantle. Here we describe measurements of I partitioning between liquid Fe alloys and liquid silicates at high pressure and temperature and propose that Xe isotopic anomalies found in modern plume rocks (that is, rocks with elevated 3He/4He ratios) result from I/Pu fractionations during early, high-pressure episodes of core formation. Our measurements demonstrate that I becomes progressively more siderophile as pressure increases, so that portions of mantle that experienced high-pressure core formation will have large I/Pu depletions not related to volatility. These portions of mantle could be the source of Xe and W anomalies observed in modern plume-derived basalts. Portions of mantle involved in early high-pressure core formation would also be rich in FeO, and hence denser than ambient mantle. This would aid the long-term preservation of these mantle portions, and potentially points to their modern manifestation within seismically slow, deep mantle reservoirs with high 3He/4He ratios.}, } @article {pmid29368704, year = {2018}, author = {Smalley, DE and Nygaard, E and Squire, K and Van Wagoner, J and Rasmussen, J and Gneiting, S and Qaderi, K and Goodsell, J and Rogers, W and Lindsey, M and Costner, K and Monk, A and Pearson, M and Haymore, B and Peatross, J}, title = {A photophoretic-trap volumetric display.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {486-490}, pmid = {29368704}, issn = {1476-4687}, abstract = {Free-space volumetric displays, or displays that create luminous image points in space, are the technology that most closely resembles the three-dimensional displays of popular fiction. Such displays are capable of producing images in 'thin air' that are visible from almost any direction and are not subject to clipping. Clipping restricts the utility of all three-dimensional displays that modulate light at a two-dimensional surface with an edge boundary; these include holographic displays, nanophotonic arrays, plasmonic displays, lenticular or lenslet displays and all technologies in which the light scattering surface and the image point are physically separate. Here we present a free-space volumetric display based on photophoretic optical trapping that produces full-colour graphics in free space with ten-micrometre image points using persistence of vision. This display works by first isolating a cellulose particle in a photophoretic trap created by spherical and astigmatic aberrations. The trap and particle are then scanned through a display volume while being illuminated with red, green and blue light. The result is a three-dimensional image in free space with a large colour gamut, fine detail and low apparent speckle. This platform, named the Optical Trap Display, is capable of producing image geometries that are currently unobtainable with holographic and light-field technologies, such as long-throw projections, tall sandtables and 'wrap-around' displays.}, } @article {pmid29368703, year = {2018}, author = {Görg, F and Messer, M and Sandholzer, K and Jotzu, G and Desbuquois, R and Esslinger, T}, title = {Enhancement and sign change of magnetic correlations in a driven quantum many-body system.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {481-485}, pmid = {29368703}, issn = {1476-4687}, abstract = {Periodic driving can be used to control the properties of a many-body state coherently and to realize phases that are not accessible in static systems. For example, exposing materials to intense laser pulses makes it possible to induce metal-insulator transitions, to control magnetic order and to generate transient superconducting behaviour well above the static transition temperature. However, pinning down the mechanisms underlying these phenomena is often difficult because the response of a material to irradiation is governed by complex, many-body dynamics. For static systems, extensive calculations have been performed to explain phenomena such as high-temperature superconductivity. Theoretical analyses of driven many-body Hamiltonians are more challenging, but approaches have now been developed, motivated by recent observations. Here we report an experimental quantum simulation in a periodically modulated hexagonal lattice and show that antiferromagnetic correlations in a fermionic many-body system can be reduced, enhanced or even switched to ferromagnetic correlations (sign reversal). We demonstrate that the description of the many-body system using an effective Floquet-Hamiltonian with a renormalized tunnelling energy remains valid in the high-frequency regime by comparing the results to measurements in an equivalent static lattice. For near-resonant driving, the enhancement and sign reversal of correlations is explained by a microscopic model of the system in which the particle tunnelling and magnetic exchange energies can be controlled independently. In combination with the observed sufficiently long lifetimes of the correlations in this system, periodic driving thus provides an alternative way of investigating unconventional pairing in strongly correlated systems experimentally.}, } @article {pmid29368660, year = {2018}, author = {Boldeanu, I and Perreault Bishop, J and Nepveu, S and Stevens, LM and Soulez, G and Kieser, TM and Lamy, A and Noiseux, N and Chartrand-Lefebvre, C}, title = {Incidental findings in CT imaging of coronary artery bypass grafts: results from a Canadian multicenter prospective cohort.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {72}, pmid = {29368660}, issn = {1756-0500}, support = {27357//Fonds de Recherche du Québec - Santé/ ; 29075//Fonds de Recherche du Québec - Santé/ ; Cycle no 4//Programme de support professoral du département de radiologie, radio-oncologie et médecine nucléaire, Université de Montréal/ ; September 2014//Programme de support professoral du département de radiologie, radio-oncologie et médecine nucléaire, Université de Montréal/ ; }, mesh = {Aged ; Canada/epidemiology ; Coronary Angiography/*methods ; Coronary Artery Bypass/*methods ; Coronary Artery Disease/diagnostic imaging/surgery ; Female ; Humans ; *Incidental Findings ; Lung Neoplasms/diagnostic imaging/epidemiology ; Male ; Middle Aged ; Prevalence ; Prospective Studies ; Pulmonary Emphysema/diagnostic imaging/epidemiology ; Tomography, X-Ray Computed/*methods ; }, abstract = {OBJECTIVE: To assess the prevalence and clinical significance of incidental findings identified during computed tomography imaging of coronary artery bypass grafts.

RESULTS: This prospective study includes 144 patients undergoing coronary graft patency assessment using computed tomography. Incidental findings were classified as significant if they were considered to need an immediate action or treatment, short-term work-up or follow-up, or minor. A total of 211 incidental findings were present in 109 (75.7%) patients. Seventy-one incidental findings (33.6%) were cardiac and 140 (66.4%) were extracardiac. Most common cardiac incidental findings were atrial dilatation [39 patients, 48 incidental findings (67.6%)] and aortic valve calcifications (7 patients, 9.9%). Among the 140 extracardiac incidental findings, the most common were lung nodules (51 patients, 54 nodules, 38.6%), and emphysema (21 patients, 15%). Thirty-six (25.7%) extracardiac incidental findings were significant and notably, 23 (63.9%) were lung nodules. Follow-up was recommended in 37 cases, among which all patients with significant lung nodules (23 patients, 62.2%). In conclusion, most common computed tomography incidental findings in patients with coronary grafts were lung nodules and emphysema.}, } @article {pmid29368646, year = {2018}, author = {Barton, DBH and Georghiou, D and Dave, N and Alghamdi, M and Walsh, TA and Louis, EJ and Foster, SS}, title = {PHENOS: a high-throughput and flexible tool for microorganism growth phenotyping on solid media.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {9}, pmid = {29368646}, issn = {1471-2180}, support = {//Wellcome Trust/United Kingdom ; BB/L022508/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Agar ; Cell Culture Techniques/instrumentation/methods ; Colony Count, Microbial/*instrumentation/*methods ; Culture Media ; Genomics/methods ; Genotype ; High-Throughput Screening Assays/*instrumentation/*methods ; Image Processing, Computer-Assisted/methods ; Phenotype ; Saccharomyces cerevisiae/cytology/*growth & development ; Software ; }, abstract = {BACKGROUND: Microbial arrays, with a large number of different strains on a single plate printed with robotic precision, underpin an increasing number of genetic and genomic approaches. These include Synthetic Genetic Array analysis, high-throughput Quantitative Trait Loci (QTL) analysis and 2-hybrid techniques. Measuring the growth of individual colonies within these arrays is an essential part of many of these techniques but is useful for any work with arrays. Measurement is typically done using intermittent imagery fed into complex image analysis software, which is not especially accurate and is challenging to use effectively. We have developed a simple and fast alternative technique that uses a pinning robot and a commonplace microplate reader to continuously measure the thickness of colonies growing on solid agar, complemented by a technique for normalizing the amount of cells initially printed to each spot of the array in the first place. We have developed software to automate the process of combining multiple sets of readings, subtracting agar absorbance, and visualizing colony thickness changes in a number of informative ways.

RESULTS: The "PHENOS" pipeline (PHENotyping On Solid media), optimized for Saccharomyces yeasts, produces highly reproducible growth curves and is particularly sensitive to low-level growth. We have empirically determined a formula to estimate colony cell count from an absorbance measurement, and shown this to be comparable with estimates from measurements in liquid. We have also validated the technique by reproducing the results of an earlier QTL study done with conventional liquid phenotyping, and found PHENOS to be considerably more sensitive.

CONCLUSIONS: "PHENOS" is a cost effective and reliable high-throughput technique for quantifying growth of yeast arrays, and is likely to be equally very useful for a range of other types of microbial arrays. A detailed guide to the pipeline and software is provided with the installation files at https://github.com/gact/phenos .}, } @article {pmid29368627, year = {2018}, author = {Raynal, JT and Bastos, BL and Vilas-Boas, PCB and Sousa, TJ and Costa-Silva, M and de Sá, MDCA and Portela, RW and Moura-Costa, LF and Azevedo, V and Meyer, R}, title = {Identification of membrane-associated proteins with pathogenic potential expressed by Corynebacterium pseudotuberculosis grown in animal serum.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {73}, pmid = {29368627}, issn = {1756-0500}, mesh = {Animals ; Bacterial Proteins/isolation & purification/*metabolism ; Cattle ; Chromatography, Liquid ; Computational Biology/methods ; Corynebacterium pseudotuberculosis/growth & development/*metabolism ; Culture Media/chemistry ; Fetal Blood ; Goats ; Membrane Proteins/isolation & purification/*metabolism ; Protein Interaction Maps ; Proteome/*metabolism ; Proteomics/*methods ; Sheep ; Tandem Mass Spectrometry ; }, abstract = {OBJECTIVE: Previous works defining antigens that might be used as vaccine targets against Corynebacterium pseudotuberculosis, which is the causative agent of sheep and goat caseous lymphadenitis, have focused on secreted proteins produced in a chemically defined culture media. Considering that such antigens might not reflect the repertoire of proteins expressed during infection conditions, this experiment aimed to investigate the membrane-associated proteins with pathogenic potential expressed by C. pseudotuberculosis grown directly in animal serum.

RESULTS: Its membrane-associated proteins have been extracted using an organic solvent enrichment methodology, followed by LC-MS/MS and bioinformatics analysis for protein identification and classification. The results revealed 22 membrane-associated proteins characterized as potentially pathogenic. An interaction network analysis indicated that the four potentially pathogenic proteins ciuA, fagA, OppA4 and OppCD were biologically connected within two distinct network pathways, which were both associated with the ABC Transporters KEGG pathway. These results suggest that C. pseudotuberculosis pathogenesis might be associated with the transport and uptake of nutrients; other seven identified potentially pathogenic membrane proteins also suggest that pathogenesis might involve events of bacterial resistance and adhesion. The proteins herein reported potentially reflect part of the protein repertoire expressed during real infection conditions and might be tested as vaccine antigens.}, } @article {pmid29368597, year = {2018}, author = {Lee, K and Kim, B and Choi, Y and Kim, S and Shin, W and Lee, S and Park, S and Kim, S and Tan, AC and Kang, J}, title = {Deep learning of mutation-gene-drug relations from the literature.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {21}, pmid = {29368597}, issn = {1471-2105}, support = {P30 CA046934/CA/NCI NIH HHS/United States ; NRF-2016M3A9A7916996//National Research Foundation of Korea/International ; NRF-2014R1A2A1A10051238//National Research Foundation of Korea/International ; }, mesh = {Antineoplastic Agents/therapeutic use ; Databases, Factual ; Drug Resistance, Neoplasm/*genetics ; Humans ; Mutation ; Neoplasms/drug therapy/genetics/pathology ; Neural Networks (Computer) ; Precision Medicine ; *Search Engine ; }, abstract = {BACKGROUND: Molecular biomarkers that can predict drug efficacy in cancer patients are crucial components for the advancement of precision medicine. However, identifying these molecular biomarkers remains a laborious and challenging task. Next-generation sequencing of patients and preclinical models have increasingly led to the identification of novel gene-mutation-drug relations, and these results have been reported and published in the scientific literature.

RESULTS: Here, we present two new computational methods that utilize all the PubMed articles as domain specific background knowledge to assist in the extraction and curation of gene-mutation-drug relations from the literature. The first method uses the Biomedical Entity Search Tool (BEST) scoring results as some of the features to train the machine learning classifiers. The second method uses not only the BEST scoring results, but also word vectors in a deep convolutional neural network model that are constructed from and trained on numerous documents such as PubMed abstracts and Google News articles. Using the features obtained from both the BEST search engine scores and word vectors, we extract mutation-gene and mutation-drug relations from the literature using machine learning classifiers such as random forest and deep convolutional neural networks. Our methods achieved better results compared with the state-of-the-art methods. We used our proposed features in a simple machine learning model, and obtained F1-scores of 0.96 and 0.82 for mutation-gene and mutation-drug relation classification, respectively. We also developed a deep learning classification model using convolutional neural networks, BEST scores, and the word embeddings that are pre-trained on PubMed or Google News data. Using deep learning, the classification accuracy improved, and F1-scores of 0.96 and 0.86 were obtained for the mutation-gene and mutation-drug relations, respectively.

CONCLUSION: We believe that our computational methods described in this research could be used as an important tool in identifying molecular biomarkers that predict drug responses in cancer patients. We also built a database of these mutation-gene-drug relations that were extracted from all the PubMed abstracts. We believe that our database can prove to be a valuable resource for precision medicine researchers.}, } @article {pmid29368592, year = {2018}, author = {Ramakrishnan Varadarajan, A and Mopuri, R and Streelman, JT and McGrath, PT}, title = {Genome-wide protein phylogenies for four African cichlid species.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {1}, pmid = {29368592}, issn = {1471-2148}, support = {R01 GM114170/GM/NIGMS NIH HHS/United States ; 1R01GM101095/GM/NIGMS NIH HHS/United States ; R21 AG050304/AG/NIA NIH HHS/United States ; R21AG050304/AG/NIA NIH HHS/United States ; R01GM114170/GM/NIGMS NIH HHS/United States ; R01 GM101095/GM/NIGMS NIH HHS/United States ; R01 DE019637/DE/NIDCR NIH HHS/United States ; 2R01DE019637/GM/NIGMS NIH HHS/United States ; }, mesh = {Africa, Eastern ; Animals ; Base Sequence ; Cichlids/*genetics ; Evolution, Molecular ; Fish Proteins/genetics ; *Genome ; Humans ; Lakes ; Phenotype ; *Phylogeny ; Receptors, Vasopressin/genetics ; Transforming Growth Factor beta/genetics ; Zebrafish/genetics ; }, abstract = {BACKGROUND: The thousands of species of closely related cichlid fishes in the great lakes of East Africa are a powerful model for understanding speciation and the genetic basis of trait variation. Recently, the genomes of five species of African cichlids representing five distinct lineages were sequenced and used to predict protein products at a genome-wide level. Here we characterize the evolutionary relationship of each cichlid protein to previously sequenced animal species.

RESULTS: We used the Treefam database, a set of preexisting protein phylogenies built using 109 previously sequenced genomes, to identify Treefam families for each protein annotated from four cichlid species: Metriaclima zebra, Astatotilapia burtoni, Pundamilia nyererei and Neolamporologus brichardi. For each of these Treefam families, we built new protein phylogenies containing each of the cichlid protein hits. Using these new phylogenies we identified the evolutionary relationship of each cichlid protein to its nearest human and zebrafish protein. This data is available either through download or through a webserver we have implemented.

CONCLUSION: These phylogenies will be useful for any cichlid researchers trying to predict biological and protein function for a given cichlid gene, understanding the evolutionary history of a given cichlid gene, identifying recently duplicated cichlid genes, or performing genome-wide analysis in cichlids that relies on using databases generated from other species.}, } @article {pmid29368590, year = {2018}, author = {Niu, J and Bi, Q and Deng, S and Chen, H and Yu, H and Wang, L and Lin, S}, title = {Identification of AUXIN RESPONSE FACTOR gene family from Prunus sibirica and its expression analysis during mesocarp and kernel development.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {21}, pmid = {29368590}, issn = {1471-2229}, support = {CAFYBB2016QA001//Central Public Interest Scientific Institution Basal Research Fund/International ; 31700586//National Natural Science Foundation of China/International ; KYQD(ZR)1701//Hainan university research funded projects/International ; }, mesh = {Amino Acid Sequence ; Fruit/genetics/growth & development ; *Gene Expression Regulation, Plant ; Multigene Family/*genetics ; Open Reading Frames ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Prunus/*genetics/metabolism ; Transcription Factors/chemistry/*genetics/metabolism ; }, abstract = {BACKGROUND: Auxin response factors (ARFs) in auxin signaling pathway are an important component that can regulate the transcription of auxin-responsive genes involved in almost all aspects of plant growth and development. To our knowledge, the comprehensive and systematic characterization of ARF genes has never been reported in Prunus sibirica, a novel woody biodiesel feedstock in China.

RESULTS: In this study, we identified 14 PsARF genes with a perfect open reading frame (ORF) in P. sibirica by using its previous transcriptomic data. Conserved motif analysis showed that all identified PsARF proteins had typical DNA-binding and ARF domain, but 5 members (PsARF3, 8 10, 16 and 17) lacked the dimerization domain. Phylogenetic analysis of the ARF proteins generated from various plant species indicated that ARFs could be categorized into 4 major groups (Class I, II, III and IV), in which all identified ARFs from P. sibirica showed a closest relationship with those from P. mume. Comparison of the expression profiles of 14 PsARF genes in different developmental stages of Siberian apricot mesocarp (SAM) and kernel (SAK) reflected distinct temporal or spatial expression patterns for PsARF genes. Additionally, based on the expressed data from fruit and seed development of multiple plant species, we identified 1514 ARF-correlated genes using weighted gene co-expression network analysis (WGCNA). And the major portion of ARF-correlated gene was characterized to be involved in protein, nucleic acid and carbohydrate metabolic, transport and regulatory processes.

CONCLUSIONS: In summary, we systematically and comprehensively analyzed the structure, expression pattern and co-expression network of ARF gene family in P. sibirica. All our findings provide theoretical foundation for the PsARF gene family and will pave the way for elucidating the precise role of PsARF genes in SAM and SAK development.}, } @article {pmid29368587, year = {2018}, author = {Krishnan, P and Ma, X and McDonald, BA and Brunner, PC}, title = {Widespread signatures of selection for secreted peptidases in a fungal plant pathogen.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {7}, pmid = {29368587}, issn = {1471-2148}, mesh = {Ascomycota/*enzymology/*genetics/pathogenicity ; Evolution, Molecular ; Gene Expression Regulation, Enzymologic ; Gene Expression Regulation, Fungal ; Genes, Fungal ; Peptide Hydrolases/*metabolism ; Phylogeny ; Plant Diseases/*microbiology ; *Selection, Genetic ; Transcriptome/genetics ; Triticum/*microbiology ; Virulence ; }, abstract = {BACKGROUND: Fungal plant pathogens secrete a large arsenal of hydrolytic enzymes during the course of infection, including peptidases. Secreted peptidases have been extensively studied for their role as effectors. In this study, we combined transcriptomics, comparative genomics and evolutionary analyses to investigate all 39 secreted peptidases in the fungal wheat pathogen Zymoseptoria tritici and its close relatives Z. pseudotritici and Z. ardabiliae.

RESULTS: RNA-seq data revealed that a majority of the secreted peptidases displayed differential transcription during the course of Z. tritici infection, indicative of specialization for different stages in the life cycle. Evolutionary analyses detected widespread evidence of adaptive evolution acting on at least 28 of the peptidases. A few peptidases displayed lineage-specific rates of molecular evolution, suggesting altered selection pressure in Z. tritici following host specialization on domesticated wheat. The peptidases belonging to MEROPS families A1 and G1 emerged as a particularly interesting group that may play key roles in host-pathogen co-evolution, host adaptation and pathogenicity. Sister genes in the A1 and G1 families showed accelerated substitution rates after gene duplications.

CONCLUSIONS: These results suggest widespread evolution of secreted peptidases leading to novel gene functions, consistent with predicted models of "escape from adaptive conflict" and "neo-functionalization". Our analyses identified candidate genes worthy of functional analyses that may encode effector functions, for example by suppressing plant defenses during the biotrophic phase of infection.}, } @article {pmid29368026, year = {2018}, author = {Borges, FM and de Paula, TO and Sarmiento, MRA and de Oliveira, MG and Pereira, MLM and Toledo, IV and Nascimento, TC and Ferreira-Machado, AB and Silva, VL and Diniz, CG}, title = {Fungal Diversity of Human Gut Microbiota Among Eutrophic, Overweight, and Obese Individuals Based on Aerobic Culture-Dependent Approach.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {726-735}, pmid = {29368026}, issn = {1432-0991}, mesh = {Ascomycota/genetics/*isolation & purification ; Aspergillus/genetics/*isolation & purification ; Basidiomycota/genetics/*isolation & purification ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*physiology ; Humans ; Obesity/genetics/*microbiology ; Overweight/genetics/*microbiology ; Penicillium/genetics/*isolation & purification ; }, abstract = {Fungi have a complex role in the intestinal tract, influencing health and disease, with dysbiosis contributing to obesity. Our objectives were to investigate fungal diversity in human gut microbiota among eutrophic, overweight, and obese. Epidemiological and nutritional information were collected from adult individuals, as well as stool samples processed for selective fungi isolation and identification by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (yeasts) or microculture (filamentous fungi). Further 18S rDNA sequencing was performed to confirm identification. The mean count of fungi was 241 CFU/g of feces. Differences in the population level of the filamentous fungi were observed within eutrophic and obese groups. Overall, 34 genera were identified. The predominant phylum was Ascomycota with 20 different genera, followed by Basidiomycota and Zygomycota. As for Ascomycota, the most prevalent species were Paecilomyces sp., Penicillium sp., Candida sp., Aspergillus sp., Fonsecaea sp., and Geotrichum sp. (76.39, 65.28, 59.72, 58.33, 12.50, and 9.72%, respectively). As for Basidiomycota, Trichosporon sp. and Rhodotorula sp. were the most prevalent (30.56 and 15.28%, respectively), and for Zygomycota, Rhizopus sp. and Mucor sp. were the most numerous (15.28 and 9.72%, respectively). As expected there is a mycobiota shift towards obesity, with slightly higher diversity associated to eutrophic individuals. This mycobiota shift seems also to be related to the nutritional behavior of the individuals, as observed that the macronutrients intake may be positively related to the different fungi occurrences. Other studies are needed to better understand relationships between mycobiota and obesity, which could be used in future obesity treatments.}, } @article {pmid29368025, year = {2018}, author = {Shi, C and Zhu, Y and Niu, Q and Wang, J and Wang, J and Zhu, W}, title = {The Changes of Colonic Bacterial Composition and Bacterial Metabolism Induced by an Early Food Introduction in a Neonatal Porcine Model.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {745-751}, pmid = {29368025}, issn = {1432-0991}, support = {2017YFD0500505//National Key R&D Program of China/ ; KYZ201722//The Fundamental Research Funds for the Central Universities, China/ ; }, mesh = {Acetates/metabolism ; Animals ; Butyrates/metabolism ; Clostridium/*metabolism ; Colon/*microbiology ; Lactobacillus/*metabolism ; Propionates/metabolism ; Swine ; Toll-Like Receptor 4/metabolism ; Valerates/metabolism ; }, abstract = {The impact of an early food introduction on the microbiota composition and microbial metabolism in colon was investigated using a new-born piglet model. At day 4 after birth, 10 litters of piglets were randomly allocated to a sow-rearing group (SR group) and a milk-replacer supplementing group (MRS group) (n = 5). A commercial milk replacer was given to the suckling piglets in the MRS group from the 4th day to the 28th day. Pyrosequencing of the V3-V4 region of the 16S rRNA genes showed that the milk replacer supplementation significantly decreased the relative abundance of Lactobacillus, Clostridium XI, Blautia, Clostridium sensustricto and Escherichia (p = 0.08) in the colon of the piglets, but significantly increased the relative abundance of Paraprevotella on the 28th day. In addition, the abundance of Rumminococcus, Clostridium XlVa, Succiniclasticum, Clostridium IV tended to increase in the MRS group. The concentrations of acetate, propionate, butyrate, valerate and branch-chain fatty acids (BCFAs) in the colonic digesta increased with the milk replacer supplementary in the MRS group. In addition, the milk replacer supplementary increased the expression level of Toll-like receptor 4 (TLR4), but decreased the expression level of interleukin-6 (IL-6) in the colonic mucosa of the piglets. In conclusion, an early food introduction can influence the gut bacterial composition and metabolism, and may further affect the intestinal health by modifying the gene transcription related to the colonic function. These findings may provide some guidelines for the early nutrition supplementation for infants during the lactation period.}, } @article {pmid29368024, year = {2018}, author = {Zhao, L and Niu, Y and Lu, T and Yin, H and Zhang, Y and Xu, L and Wang, Y and Chen, H}, title = {Metagenomic Analysis of the Jinding Duck Fecal Virome.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {658-665}, pmid = {29368024}, issn = {1432-0991}, support = {2016YFD0500800//The National Key Research and Development Program of China/ ; Y2016PT41//Chinese Academy of Agricultural Sciences Fundamental Scientific Research Funds/ ; }, mesh = {Animals ; DNA Viruses/genetics/isolation & purification ; Ducks ; Feces/*virology ; Genome, Viral/genetics ; Metagenomics/*methods ; RNA Viruses/genetics/isolation & purification ; Viruses/*genetics/*isolation & purification ; }, abstract = {Ducks play an important role in transmitting and maintaining mammalian viruses in nature, and are a reservoir host of many animal viruses. We analyzed the fecal virome of four strains (A, B, C, and D) of ducks living in isolation by using metagenomic analysis. The feces of the ducks tested contained 18 animal virus families. The percentage values of RNA virus reads, compared to the total animal virus reads in each of the four strains were 96.96% (A), 97.30% (B), 98.01 (C), and 67.49% (D), and were mainly from Orthomyxoviridae, Mimiviridae, Bunyaviridae, Picobirnaviridae, and Reoviridae. Meanwhile, the minority of DNA virus reads were related to Herpesviridae, Adenoviridae, Iridoviridae, and other, low abundance viral families. The percentage values of Orthomyxoviridae, Mimiviridae, Bunyaviridae, Picobirnaviridae, and Herpesviridae reads were not significantly different among strains A, B, and C; however, there were marked differences in the abundance of these reads in strain D. In summary, this study provides an unbiased examination of the viral diversity in the feces of four strains of ducks in specific-pathogen-free periods, and highlights the variation in the percentage of viral families present. These results can be used as a reference for detecting duck viral pathogens and predicting zoonotic potential.}, } @article {pmid29367423, year = {2018}, author = {Samanta, D and Park, Y and Ni, X and Li, H and Zahnow, CA and Gabrielson, E and Pan, F and Semenza, GL}, title = {Chemotherapy induces enrichment of CD47+/CD73+/PDL1+ immune evasive triple-negative breast cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1239-E1248}, pmid = {29367423}, issn = {1091-6490}, mesh = {5'-Nucleotidase/genetics/*metabolism ; Animals ; Antineoplastic Agents/*pharmacology ; Apoptosis ; B7-H1 Antigen/genetics/*metabolism ; CD47 Antigen/genetics/*metabolism ; Female ; GPI-Linked Proteins/genetics/metabolism ; Gene Expression Regulation, Neoplastic/drug effects ; Humans ; Hypoxia-Inducible Factor 1/genetics/*metabolism ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; T-Lymphocytes/immunology/metabolism/pathology ; Triple Negative Breast Neoplasms/drug therapy/*immunology/metabolism ; Tumor Cells, Cultured ; Tumor Escape/*immunology ; Xenograft Model Antitumor Assays ; }, abstract = {Triple-negative breast cancer (TNBC) is treated with cytotoxic chemotherapy and is often characterized by early relapse and metastasis. To form a secondary (recurrent and/or metastatic) tumor, a breast cancer cell must evade the innate and adaptive immune systems. CD47 enables cancer cells to evade killing by macrophages, whereas CD73 and PDL1 mediate independent mechanisms of evasion of cytotoxic T lymphocytes. Here, we report that treatment of human or murine TNBC cells with carboplatin, doxorubicin, gemcitabine, or paclitaxel induces the coordinate transcriptional induction of CD47, CD73, and PDL1 mRNA and protein expression, leading to a marked increase in the percentage of CD47+CD73+PDL1+ breast cancer cells. Genetic or pharmacological inhibition of hypoxia-inducible factors (HIFs) blocked chemotherapy-induced enrichment of CD47+CD73+PDL1+ TNBC cells, which were also enriched in the absence of chemotherapy by incubation under hypoxic conditions, leading to T cell anergy or death. Treatment of mice with cytotoxic chemotherapy markedly increased the intratumoral ratio of regulatory/effector T cells, an effect that was abrogated by HIF inhibition. Our results delineate an HIF-dependent transcriptional mechanism contributing to TNBC progression and suggest that combining chemotherapy with an HIF inhibitor may prevent countertherapeutic induction of proteins that mediate evasion of innate and adaptive antitumor immunity.}, } @article {pmid29367422, year = {2018}, author = {Beer, KB and Rivas-Castillo, J and Kuhn, K and Fazeli, G and Karmann, B and Nance, JF and Stigloher, C and Wehman, AM}, title = {Extracellular vesicle budding is inhibited by redundant regulators of TAT-5 flippase localization and phospholipid asymmetry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1127-E1136}, pmid = {29367422}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; R03 AI099555/AI/NIAID NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/genetics/*metabolism ; Adenosine Triphosphate/metabolism ; Animals ; Animals, Genetically Modified/genetics/growth & development/*metabolism ; Caenorhabditis elegans/embryology/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Membrane/*metabolism ; Embryo, Nonmammalian/cytology/*metabolism ; Endocytosis/physiology ; Extracellular Vesicles/*metabolism ; Phosphatidylethanolamines/*metabolism ; }, abstract = {Cells release extracellular vesicles (EVs) that mediate intercellular communication and repair damaged membranes. Despite the pleiotropic functions of EVs in vitro, their in vivo function is debated, largely because it is unclear how to induce or inhibit their formation. In particular, the mechanisms of EV release by plasma membrane budding or ectocytosis are poorly understood. We previously showed that TAT-5 phospholipid flippase activity maintains the asymmetric localization of the lipid phosphatidylethanolamine (PE) in the plasma membrane and inhibits EV budding by ectocytosis in Caenorhabditis elegans However, no proteins that inhibit ectocytosis upstream of TAT-5 were known. Here, we identify TAT-5 regulators associated with retrograde endosomal recycling: PI3Kinase VPS-34, Beclin1 homolog BEC-1, DnaJ protein RME-8, and the uncharacterized Dopey homolog PAD-1. PI3Kinase, RME-8, and semiredundant sorting nexins are required for the plasma membrane localization of TAT-5, which is important to maintain PE asymmetry and inhibit EV release. PAD-1 does not directly regulate TAT-5 localization, but is required for the lipid flipping activity of TAT-5. PAD-1 also has roles in endosomal trafficking with the GEF-like protein MON-2, which regulates PE asymmetry and EV release redundantly with sorting nexins independent of the core retromer. Thus, in addition to uncovering redundant intracellular trafficking pathways, our study identifies additional proteins that regulate EV release. This work pinpoints TAT-5 and PE as key regulators of plasma membrane budding, further supporting the model that PE externalization drives ectocytosis.}, } @article {pmid29367421, year = {2018}, author = {Stewart, MD and Zelin, E and Dhall, A and Walsh, T and Upadhyay, E and Corn, JE and Chatterjee, C and King, MC and Klevit, RE}, title = {BARD1 is necessary for ubiquitylation of nucleosomal histone H2A and for transcriptional regulation of estrogen metabolism genes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1316-1321}, pmid = {29367421}, issn = {1091-6490}, support = {R01 CA175716/CA/NCI NIH HHS/United States ; R35 CA197458/CA/NCI NIH HHS/United States ; R01 GM110430/GM/NIGMS NIH HHS/United States ; R01 GM088055/GM/NIGMS NIH HHS/United States ; T32 CA080416/CA/NCI NIH HHS/United States ; }, mesh = {BRCA1 Protein/genetics/metabolism ; Breast Neoplasms/genetics ; Cytochrome P-450 CYP1A1/genetics/metabolism ; Cytochrome P-450 CYP3A/genetics/metabolism ; Estrogens/genetics/*metabolism ; Female ; Gene Expression Regulation ; Histones/genetics/*metabolism ; Humans ; Male ; Mutation, Missense ; Nucleosomes/metabolism ; Protein Domains ; Tumor Suppressor Proteins/chemistry/*genetics/*metabolism ; Ubiquitin-Protein Ligases/chemistry/*genetics/*metabolism ; Ubiquitination ; }, abstract = {Missense mutations that disrupt the RING domain of the tumor suppressor gene BRCA1 lead to increased risk of breast and ovarian cancer. The BRCA1 RING domain is a ubiquitin ligase, whose structure and function rely critically on forming a heterodimer with BARD1, which also harbors a RING domain. The function of the BARD1 RING domain is unknown. In families severely affected with breast cancer, we identified inherited BARD1 missense mutations Cys53Trp, Cys71Tyr, and Cys83Arg that alter three zinc-binding residues of the BARD1 RING domain. Each of these mutant BARD1 proteins retained the ability to form heterodimeric complexes with BRCA1 to make an active ubiquitin ligase, but the mutant BRCA1/BARD1 complexes were deficient in binding to nucleosomes and in ubiquitylating histone H2A. The BARD1 mutations also caused loss of transcriptional repression of BRCA1-regulated estrogen metabolism genes CYP1A1 and CYP3A4; breast epithelial cells edited to create heterozygous loss of BARD1 showed significantly higher expression of CYP1A1 and CYP3A4 Reintroduction of wild-type BARD1 into these cells restored CYP1A1 and CYP3A4 transcription to normal levels, but introduction of the cancer-predisposing BARD1 RING mutants failed to do so. These results indicate that an intact BARD1 RING domain is critical to BRCA1/BARD1 binding to nucleosomes and hence to ubiquitylation of histone H2A and also critical to transcriptional repression of BRCA1-regulated genes active in estrogen metabolism.}, } @article {pmid29367420, year = {2018}, author = {Bocanegra Evans, H and Hamed, AM and Gorumlu, S and Doosttalab, A and Aksak, B and Chamorro, LP and Castillo, L}, title = {Engineered bio-inspired coating for passive flow control.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1210-1214}, pmid = {29367420}, issn = {1091-6490}, abstract = {Flow separation and vortex shedding are some of the most common phenomena experienced by bluff bodies under relative motion with the surrounding medium. They often result in a recirculation bubble in regions with adverse pressure gradient, which typically reduces efficiency in vehicles and increases loading on structures. Here, the ability of an engineered coating to manipulate the large-scale recirculation region was tested in a separated flow at moderate momentum thickness Reynolds number, [Formula: see text] We show that the coating, composed of uniformly distributed cylindrical pillars with diverging tips, successfully reduces the size of, and shifts downstream, the separation bubble. Despite the so-called roughness parameter, [Formula: see text], falling within the hydrodynamic smooth regime, the coating is able to modulate the large-scale recirculating motion. Remarkably, this modulation does not induce noticeable changes in the near-wall turbulence levels. Supported with experimental data and theoretical arguments based on the averaged equations of motion, we suggest that the inherent mechanism responsible for the bubble modulation is essentially unsteady suction and blowing controlled by the increasing cross-section of the tips. The coating can be easily fabricated and installed and works under dry and wet conditions, increasing its potential impact on a diverse range of applications.}, } @article {pmid29367419, year = {2018}, author = {Raison, CL and Raichlen, DA}, title = {An evolutionary perspective on nutrition and social decision making.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1331}, pmid = {29367419}, issn = {1091-6490}, mesh = {*Decision Making ; *Nutritional Status ; }, } @article {pmid29367418, year = {2018}, author = {Park, SQ and Schmid, SM}, title = {Reply to Raison and Raichlen: Why does nutrition impact social decision making?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1332-E1333}, pmid = {29367418}, issn = {1091-6490}, mesh = {*Decision Making ; *Nutritional Status ; }, } @article {pmid29367175, year = {2018}, author = {Yang, L and Yurkovich, JT and King, ZA and Palsson, BO}, title = {Modeling the multi-scale mechanisms of macromolecular resource allocation.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {8-15}, doi = {10.1016/j.mib.2018.01.002}, pmid = {29367175}, issn = {1879-0364}, abstract = {As microbes face changing environments, they dynamically allocate macromolecular resources to produce a particular phenotypic state. Broad 'omics' data sets have revealed several interesting phenomena regarding how the proteome is allocated under differing conditions, but the functional consequences of these states and how they are achieved remain open questions. Various types of multi-scale mathematical models have been used to elucidate the genetic basis for systems-level adaptations. In this review, we outline several different strategies by which microbes accomplish resource allocation and detail how mathematical models have aided in our understanding of these processes. Ultimately, such modeling efforts have helped elucidate the principles of proteome allocation and hold promise for further discovery.}, } @article {pmid29366937, year = {2018}, author = {Strous, M and Sharp, C}, title = {Designer microbiomes for environmental, energy and health biotechnology.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {117-123}, doi = {10.1016/j.mib.2017.12.007}, pmid = {29366937}, issn = {1879-0364}, mesh = {*Biotechnology ; *Environmental Microbiology ; Gastrointestinal Microbiome ; Genomics/methods ; Humans ; Intestines/*microbiology ; *Microbiota ; Proteomics ; Waste Water/microbiology ; }, abstract = {Biotechnology conventionally uses pure strains of microorganisms to realize a desired conversion. The design of functional microbiomes is becoming a powerful alternative for when an aseptic environment is not an option, either for economic reasons or if the environment is intrinsically open. Rapid technological developments in combined -omics approaches is enabling the engineering and optimization of highly complex microbiomes. This review outlines emerging principles of design and provides examples of successful approaches and interventions in wastewater treatment, bioenergy production and the human intestinal microbiome.}, } @article {pmid29366829, year = {2018}, author = {Sharma, PP and Baker, CM and Cosgrove, JG and Johnson, JE and Oberski, JT and Raven, RJ and Harvey, MS and Boyer, SL and Giribet, G}, title = {A revised dated phylogeny of scorpions: Phylogenomic support for ancient divergence of the temperate Gondwanan family Bothriuridae.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {37-45}, doi = {10.1016/j.ympev.2018.01.003}, pmid = {29366829}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Biodiversity ; Biological Evolution ; Fossils ; Genetic Loci ; Phylogeny ; Scorpions/*classification/genetics ; }, abstract = {The scorpion family Bothriuridae occupies a subset of landmasses formerly constituting East and West temperate Gondwana, but its relationship to other scorpion families is in question. Whereas morphological data have strongly supported a sister group relationship of Bothriuridae and the superfamily Scorpionoidea, a recent phylogenomic analysis recovered a basal placement of bothriurids within Iurida, albeit sampling only a single exemplar. Here we reexamined the phylogenetic placement of the family Bothriuridae, sampling six bothriurid exemplars representing both East and West Gondwana, using transcriptomic data. Our results demonstrate that the sister group relationship of Bothriuridae to the clade ("Chactoidea" + Scorpionoidea) is supported by the inclusion of additional bothriurid taxa, and that this placement is insensitive to matrix completeness or partitioning by evolutionary rate. We also estimated divergence times within the order Scorpiones using multiple fossil calibrations, to infer whether the family Bothriuridae is sufficiently old to be characterized as a true Gondwanan lineage. We show that scorpions underwent ancient diversification between the Devonian and early Carboniferous. The age interval of the bothriurids sampled (a derived group that excludes exemplars from South Africa) spans the timing of breakup of temperate Gondwana.}, } @article {pmid29366821, year = {2018}, author = {Merchant, B and Edelstein-Keshet, L and Feng, JJ}, title = {A Rho-GTPase based model explains spontaneous collective migration of neural crest cell clusters.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, doi = {10.1016/j.ydbio.2018.01.013}, pmid = {29366821}, issn = {1095-564X}, abstract = {We propose a model to explain the spontaneous collective migration of neural crest cells in the absence of an external gradient of chemoattractants. The model is based on the dynamical interaction between Rac1 and RhoA that is known to regulate the polarization, contact inhibition and co-attraction of neural crest cells. Coupling the reaction-diffusion equations for active and inactive Rac1 and RhoA on the cell membrane with a mechanical model for the overdamped motion of membrane vertices, we show that co-attraction and contact inhibition cooperate to produce persistence of polarity in a cluster of neural crest cells by suppressing the random onset of Rac1 hotspots that may mature into new protrusion fronts. This produces persistent directional migration of cell clusters in corridors. Our model confirms a prior hypothesis that co-attraction and contact inhibition are key to spontaneous collective migration, and provides an explanation of their cooperative working mechanism in terms of Rho GTPase signaling. The model shows that the spontaneous migration is more robust for larger clusters, and is most efficient in a corridor of optimal confinement.}, } @article {pmid29366606, year = {2018}, author = {Paigen, K and Petkov, PM}, title = {PRDM9 and Its Role in Genetic Recombination.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {291-300}, pmid = {29366606}, issn = {0168-9525}, support = {P01 GM099640/GM/NIGMS NIH HHS/United States ; P30 CA034196/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; DNA Breaks, Double-Stranded ; Eukaryotic Cells/cytology/enzymology ; *Genome ; Histone-Lysine N-Methyltransferase/*genetics/metabolism ; Histones/*genetics/metabolism ; Humans ; Isoenzymes/genetics/metabolism ; *Meiosis ; Methylation ; Mice ; Nucleosomes/enzymology/genetics ; Protein Domains ; *Recombination, Genetic ; }, abstract = {PRDM9 is a zinc finger protein that binds DNA at specific locations in the genome where it trimethylates histone H3 at lysines 4 and 36 at surrounding nucleosomes. During meiosis in many species, including humans and mice where PRDM9 has been most intensely studied, these actions determine the location of recombination hotspots, where genetic recombination occurs. In addition, PRDM9 facilitates the association of hotspots with the chromosome axis, the site of the programmed DNA double-strand breaks (DSBs) that give rise to genetic exchange between chromosomes. In the absence of PRDM9 DSBs are not properly repaired. Collectively, these actions determine patterns of genetic linkage and the possibilities for chromosome reorganization over successive generations.}, } @article {pmid29366605, year = {2018}, author = {Sieber, P and Platzer, M and Schuster, S}, title = {The Definition of Open Reading Frame Revisited.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {167-170}, doi = {10.1016/j.tig.2017.12.009}, pmid = {29366605}, issn = {0168-9525}, mesh = {5' Untranslated Regions/*genetics ; Codon, Initiator/*genetics ; Codon, Terminator/*genetics ; Computational Biology/methods ; DNA/genetics ; Eukaryotic Cells/metabolism ; Exons/genetics ; Open Reading Frames/*genetics ; Prokaryotic Cells/metabolism ; }, abstract = {The term open reading frame (ORF) is of central importance to gene finding. Surprisingly, at least three definitions are in use. We discuss several molecular biological and bioinformatics aspects, and we recommend using the definition in which an ORF is bounded by stop codons.}, } @article {pmid29365173, year = {2018}, author = {Gou, X and Bian, Y and Zhang, A and Zhang, H and Wang, B and Lv, R and Li, J and Zhu, B and Gong, L and Liu, B}, title = {Transgenerationally Precipitated Meiotic Chromosome Instability Fuels Rapid Karyotypic Evolution and Phenotypic Diversity in an Artificially Constructed Allotetraploid Wheat (AADD).}, journal = {Molecular biology and evolution}, volume = {35}, number = {5}, pages = {1078-1091}, pmid = {29365173}, issn = {1537-1719}, abstract = {Although a distinct karyotype with defined chromosome number and structure characterizes each biological species, it is intrinsically labile. Polyploidy or whole-genome duplication has played a pervasive and ongoing role in the evolution of all eukaryotes, and is the most dramatic force known to cause rapid karyotypic reconfiguration, especially at the initial stage. However, issues concerning transgenerational propagation of karyotypic heterogeneity and its translation to phenotypic diversity in nascent allopolyploidy, at the population level, have yet to be studied in detail. Here, we report a large-scale examination of transgenerationally propagated karyotypic heterogeneity and its phenotypic manifestation in an artificially constructed allotetraploid with a genome composition of AADD, that is, involving two of the three progenitor genomes of polyploid wheat. Specifically, we show that 1) massive organismal karyotypic heterogeneity is precipitated after 12 consecutive generations of selfing from a single euploid founder individual, 2) there exist dramatic differences in aptitudes between subgenomes and among chromosomes for whole-chromosome gain and/or loss and structural variations, 3) majority of the numerical and structural chromosomal variations are concurrent due to mutual contingency and possible functional constraint, 4) purposed and continuous selection and propagation for euploidy over generations did not result in enhanced karyotype stabilization, and 5) extent of karyotypic variation correlates with variability of phenotypic manifestation. Together, our results document that allopolyploidization catalyzes rampant and transgenerationally heritable organismal karyotypic heterogeneity that drives population-level phenotypic diversification, which lends fresh empirical support to the still contentious notion that whole-genome duplication enhances organismal evolvability.}, } @article {pmid29365169, year = {2018}, author = {Kasinathan, S and Henikoff, S}, title = {Non-B-Form DNA Is Enriched at Centromeres.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {949-962}, pmid = {29365169}, issn = {1537-1719}, support = {T32 GM007266/GM/NIGMS NIH HHS/United States ; }, abstract = {Animal and plant centromeres are embedded in repetitive "satellite" DNA, but are thought to be epigenetically specified. To define genetic characteristics of centromeres, we surveyed satellite DNA from diverse eukaryotes and identified variation in <10-bp dyad symmetries predicted to adopt non-B-form conformations. Organisms lacking centromeric dyad symmetries had binding sites for sequence-specific DNA-binding proteins with DNA-bending activity. For example, human and mouse centromeres are depleted for dyad symmetries, but are enriched for non-B-form DNA and are associated with binding sites for the conserved DNA-binding protein CENP-B, which is required for artificial centromere function but is paradoxically nonessential. We also detected dyad symmetries and predicted non-B-form DNA structures at neocentromeres, which form at ectopic loci. We propose that centromeres form at non-B-form DNA because of dyad symmetries or are strengthened by sequence-specific DNA binding proteins. This may resolve the CENP-B paradox and provide a general basis for centromere specification.}, } @article {pmid29365145, year = {2018}, author = {Cerón-Romero, MA and Nwaka, E and Owoade, Z and Katz, LA}, title = {PhyloChromoMap, a Tool for Mapping Phylogenomic History along Chromosomes, Reveals the Dynamic Nature of Karyotype Evolution in Plasmodium falciparum.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {553-561}, pmid = {29365145}, issn = {1759-6653}, support = {R15 GM113177/GM/NIGMS NIH HHS/United States ; }, mesh = {Chromosome Mapping/*methods ; *Evolution, Molecular ; *Genes, Protozoan ; Humans ; Karyotype ; Karyotyping/methods ; Malaria, Falciparum/*parasitology ; *Phylogeny ; Plasmodium falciparum/*genetics ; Protozoan Proteins/genetics ; }, abstract = {The genome of Plasmodium falciparum, the causative agent of malaria in Africa, has been extensively studied since it was first fully sequenced in 2002. However, many open questions remain, including understanding the chromosomal context of molecular evolutionary changes (e.g., relationship between chromosome map and phylogenetic conservation, patterns of gene duplication, and patterns of selection). Here, we present PhyloChromoMap, a method that generates a phylogenomic map of chromosomes from a custom-built bioinformatics pipeline. Using P. falciparum 3D7 as a model, we analyze 2,116 genes with homologs in up to 941 diverse eukaryotic, bacterial and archaeal lineages. We estimate the level of conservation along chromosomes based on conservation across clades, and identify "young" regions (i.e., those with recent or fast evolving genes) that are enriched in subtelomeric regions as compared with internal regions. We also demonstrate that patterns of molecular evolution for paralogous genes differ significantly depending on their location as younger paralogs tend to be found in subtelomeric regions whereas older paralogs are enriched in internal regions. Combining these observations with analyses of synteny, we demonstrate that subtelomeric regions are actively shuffled among chromosome ends, which is consistent with the hypothesis that these regions are prone to ectopic recombination. We also assess patterns of selection by comparing dN/dS ratios of gene family members in subtelomeric versus internal regions, and we include the important antigenic gene family var. These analyses illustrate the highly dynamic nature of the karyotype of P. falciparum, and provide a method for exploring genome dynamics in other lineages.}, } @article {pmid29365084, year = {2018}, author = {Dewachter, L and Verstraeten, N and Fauvart, M and Michiels, J}, title = {An integrative view of cell cycle control in Escherichia coli.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {2}, pages = {116-136}, doi = {10.1093/femsre/fuy005}, pmid = {29365084}, issn = {1574-6976}, mesh = {Cell Cycle/genetics/*physiology ; Escherichia coli/cytology/genetics/*physiology ; Genome, Bacterial ; }, abstract = {Bacterial proliferation depends on the cells' capability to proceed through consecutive rounds of the cell cycle. The cell cycle consists of a series of events during which cells grow, copy their genome, partition the duplicated DNA into different cell halves and, ultimately, divide to produce two newly formed daughter cells. Cell cycle control is of the utmost importance to maintain the correct order of events and safeguard the integrity of the cell and its genomic information. This review covers insights into the regulation of individual key cell cycle events in Escherichia coli. The control of initiation of DNA replication, chromosome segregation and cell division is discussed. Furthermore, we highlight connections between these processes. Although detailed mechanistic insight into these connections is largely still emerging, it is clear that the different processes of the bacterial cell cycle are coordinated to one another. This careful coordination of events ensures that every daughter cell ends up with one complete and intact copy of the genome, which is vital for bacterial survival.}, } @article {pmid29364880, year = {2018}, author = {Tetarenko, BE and Lasota, JP and Heinke, CO and Dubus, G and Sivakoff, GR}, title = {Strong disk winds traced throughout outbursts in black-hole X-ray binaries.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {69-72}, doi = {10.1038/nature25159}, pmid = {29364880}, issn = {1476-4687}, abstract = {Recurring outbursts associated with matter flowing onto compact stellar remnants (such as black holes, neutron stars and white dwarfs) in close binary systems provide a way of constraining the poorly understood accretion process. The light curves of these outbursts are shaped by the efficiency of angular-momentum (and thus mass) transport in the accretion disks, which has traditionally been encoded in a viscosity parameter, α. Numerical simulations of the magneto-rotational instability that is believed to be the physical mechanism behind this transport yield values of α of roughly 0.1-0.2, consistent with values determined from observations of accreting white dwarfs. Equivalent viscosity parameters have hitherto not been estimated for disks around neutron stars or black holes. Here we report the results of an analysis of archival X-ray light curves of 21 outbursts in black-hole X-ray binaries. By applying a Bayesian approach to a model of accretion, we determine corresponding values of α of around 0.2-1.0. These high values may be interpreted as an indication either of a very high intrinsic rate of angular-momentum transport in the disk, which could be sustained by the magneto-rotational instability only if a large-scale magnetic field threads the disk, or that mass is being lost from the disk through substantial outflows, which strongly shape the outburst in the black-hole X-ray binary. The lack of correlation between our estimates of α and the accretion state of the binaries implies that such outflows can remove a substantial fraction of the disk mass in all accretion states and therefore suggests that the outflows correspond to magnetically driven disk winds rather than thermally driven ones, which require specific radiative conditions.}, } @article {pmid29364879, year = {2018}, author = {Morscher, RJ and Ducker, GS and Li, SH and Mayer, JA and Gitai, Z and Sperl, W and Rabinowitz, JD}, title = {Mitochondrial translation requires folate-dependent tRNA methylation.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {128-132}, pmid = {29364879}, issn = {1476-4687}, support = {DP1 DK113643/DK/NIDDK NIH HHS/United States ; F31 DK113653/DK/NIDDK NIH HHS/United States ; R01 CA163591/CA/NCI NIH HHS/United States ; R01 GM107384/GM/NIGMS NIH HHS/United States ; DP1 AI124669/AI/NIAID NIH HHS/United States ; }, mesh = {Aminohydrolases/metabolism ; Biocatalysis ; Carrier Proteins/metabolism ; Codon/genetics ; Electron Transport ; Folic Acid/*metabolism ; Folic Acid Antagonists/pharmacology ; GTP-Binding Proteins/metabolism ; Glycine Hydroxymethyltransferase/deficiency/metabolism ; Guanosine/metabolism ; HCT116 Cells ; HEK293 Cells ; Humans ; Leucine/genetics ; Lysine/genetics ; Methylation/drug effects ; Methylenetetrahydrofolate Dehydrogenase (NADP)/metabolism ; Mitochondria/drug effects/enzymology/*metabolism ; Multifunctional Enzymes/metabolism ; Oxidative Phosphorylation/drug effects ; *Protein Biosynthesis ; RNA, Transfer/*chemistry/genetics/*metabolism ; Ribosomes/metabolism ; Sarcosine/metabolism ; Tetrahydrofolates/metabolism ; Thymine Nucleotides/biosynthesis ; }, abstract = {Folates enable the activation and transfer of one-carbon units for the biosynthesis of purines, thymidine and methionine. Antifolates are important immunosuppressive and anticancer agents. In proliferating lymphocytes and human cancers, mitochondrial folate enzymes are particularly strongly upregulated. This in part reflects the need for mitochondria to generate one-carbon units and export them to the cytosol for anabolic metabolism. The full range of uses of folate-bound one-carbon units in the mitochondrial compartment itself, however, has not been thoroughly explored. Here we show that loss of the catalytic activity of the mitochondrial folate enzyme serine hydroxymethyltransferase 2 (SHMT2), but not of other folate enzymes, leads to defective oxidative phosphorylation in human cells due to impaired mitochondrial translation. We find that SHMT2, presumably by generating mitochondrial 5,10-methylenetetrahydrofolate, provides methyl donors to produce the taurinomethyluridine base at the wobble position of select mitochondrial tRNAs. Mitochondrial ribosome profiling in SHMT2-knockout human cells reveals that the lack of this modified base causes defective translation, with preferential mitochondrial ribosome stalling at certain lysine (AAG) and leucine (UUG) codons. This results in the impaired expression of respiratory chain enzymes. Stalling at these specific codons also occurs in certain inborn errors of mitochondrial metabolism. Disruption of whole-cell folate metabolism, by either folate deficiency or antifolate treatment, also impairs the respiratory chain. In summary, mammalian mitochondria use folate-bound one-carbon units to methylate tRNA, and this modification is required for mitochondrial translation and thus oxidative phosphorylation.}, } @article {pmid29364878, year = {2018}, author = {Mao, K and Baptista, AP and Tamoutounour, S and Zhuang, L and Bouladoux, N and Martins, AJ and Huang, Y and Gerner, MY and Belkaid, Y and Germain, RN}, title = {Innate and adaptive lymphocytes sequentially shape the gut microbiota and lipid metabolism.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {255-259}, pmid = {29364878}, issn = {1476-4687}, support = {1K99AI123350-01A1/AO/NIAID NIH HHS/United States ; }, mesh = {*Adaptive Immunity ; Animals ; CD4-Positive T-Lymphocytes/immunology ; Epithelial Cells/cytology/immunology ; Gastrointestinal Microbiome/*immunology ; Homeodomain Proteins/genetics ; Homeostasis ; *Immunity, Innate ; Inflammation/immunology/microbiology/pathology ; Interleukin-23/immunology ; Interleukins/biosynthesis/immunology ; Intestine, Small/*immunology/metabolism/*microbiology ; *Lipid Metabolism ; Lymphocyte Activation ; Lymphocytes/*immunology ; Male ; Mice ; Monocytes/metabolism ; Phosphorylation ; Receptors, CCR2/metabolism ; STAT3 Transcription Factor/metabolism ; Symbiosis ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; Weaning ; }, abstract = {The mammalian gut is colonized by numerous microorganisms collectively termed the microbiota, which have a mutually beneficial relationship with their host. Normally, the gut microbiota matures during ontogeny to a state of balanced commensalism marked by the absence of adverse inflammation. Subsets of innate lymphoid cells (ILCs) and conventional T cells are considered to have redundant functions in containment and clearance of microbial pathogens, but how these two major lymphoid-cell populations each contribute to shaping the mature commensal microbiome and help to maintain tissue homeostasis has not been determined. Here we identify, using advanced multiplex quantitative imaging methods, an extensive and persistent phosphorylated-STAT3 signature in group 3 ILCs and intestinal epithelial cells that is induced by interleukin (IL)-23 and IL-22 in mice that lack CD4+ T cells. By contrast, in immune-competent mice, phosphorylated-STAT3 activation is induced only transiently by microbial colonization at weaning. This early signature is extinguished as CD4+ T cell immunity develops in response to the expanding commensal burden. Physiologically, the persistent IL-22 production from group 3 ILCs that occurs in the absence of adaptive CD4+ T-cell activity results in impaired host lipid metabolism by decreasing lipid transporter expression in the small bowel. These findings provide new insights into how innate and adaptive lymphocytes operate sequentially and in distinct ways during normal development to establish steady-state commensalism and tissue metabolic homeostasis.}, } @article {pmid29364877, year = {2018}, author = {Shen, Q and Zhang, Q and Shi, Y and Shi, Q and Jiang, Y and Gu, Y and Li, Z and Li, X and Zhao, K and Wang, C and Li, N and Cao, X}, title = {Tet2 promotes pathogen infection-induced myelopoiesis through mRNA oxidation.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {123-127}, doi = {10.1038/nature25434}, pmid = {29364877}, issn = {1476-4687}, mesh = {3' Untranslated Regions/genetics ; 5-Methylcytosine/analogs & derivatives/metabolism ; Adenosine Deaminase/metabolism ; Animals ; Bone Marrow Cells/immunology ; DNA-Binding Proteins/deficiency/*metabolism ; Epigenesis, Genetic ; Female ; Gene Expression Regulation ; Immunity, Innate ; Mice ; *Myelopoiesis/genetics ; Nucleic Acid Conformation ; Oxidation-Reduction ; Proto-Oncogene Proteins/deficiency/*metabolism ; RNA, Double-Stranded/chemistry/genetics/metabolism ; RNA, Messenger/*chemistry/genetics/*metabolism ; Sepsis/*genetics/*microbiology ; Suppressor of Cytokine Signaling 3 Protein/genetics ; Transcriptome/genetics ; }, abstract = {Varieties of RNA modification form the epitranscriptome for post-transcriptional regulation. 5-Methylcytosine (5-mC) is a sparse RNA modification in messenger RNA (mRNA) under physiological conditions. The function of RNA 5-hydroxymethylcytosine (5-hmC) oxidized by ten-eleven translocation (Tet) proteins in Drosophila has been revealed more recently. However, the turnover and function of 5-mC in mammalian mRNA have been largely unknown. Tet2 suppresses myeloid malignancies mostly in an enzymatic activity-dependent manner, and is important in resolving inflammatory response in an enzymatic activity-independent way. Myelopoiesis is a common host immune response in acute and chronic infections; however, its epigenetic mechanism needs to be identified. Here we demonstrate that Tet2 promotes infection-induced myelopoiesis in an mRNA oxidation-dependent manner through Adar1-mediated repression of Socs3 expression at the post-transcription level. Tet2 promotes both abdominal sepsis-induced emergency myelopoiesis and parasite-induced mast cell expansion through decreasing mRNA levels of Socs3, a key negative regulator of the JAK-STAT pathway that is critical for cytokine-induced myelopoiesis. Tet2 represses Socs3 expression through Adar1, which binds and destabilizes Socs3 mRNA in a RNA editing-independent manner. For the underlying mechanism of Tet2 regulation at the mRNA level, Tet2 mediates oxidation of 5-mC in mRNA. Tet2 deficiency leads to the transcriptome-wide appearance of methylated cytosines, including ones in the 3' untranslated region of Socs3, which influences double-stranded RNA formation for Adar1 binding, probably through cytosine methylation-specific readers, such as RNA helicases. Our study reveals a previously unknown regulatory role of Tet2 at the epitranscriptomic level, promoting myelopoiesis during infection in the mammalian system by decreasing 5-mCs in mRNAs. Moreover, the inhibitory function of cytosine methylation on double-stranded RNA formation and Adar1 binding in mRNA reveals its new physiological role in the mammalian system.}, } @article {pmid29364876, year = {2018}, author = {Kauffman, KM and Hussain, FA and Yang, J and Arevalo, P and Brown, JM and Chang, WK and VanInsberghe, D and Elsherbini, J and Sharma, RS and Cutler, MB and Kelly, L and Polz, MF}, title = {A major lineage of non-tailed dsDNA viruses as unrecognized killers of marine bacteria.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {118-122}, doi = {10.1038/nature25474}, pmid = {29364876}, issn = {1476-4687}, mesh = {Aquatic Organisms/*virology ; Archaea/virology ; Bacteria/*virology ; Bias ; Capsid Proteins/metabolism ; DNA Viruses/*classification/genetics/isolation & purification/*pathogenicity ; Metagenomics ; *Phylogeny ; Vibrio/virology ; }, abstract = {The most abundant viruses on Earth are thought to be double-stranded DNA (dsDNA) viruses that infect bacteria. However, tailed bacterial dsDNA viruses (Caudovirales), which dominate sequence and culture collections, are not representative of the environmental diversity of viruses. In fact, non-tailed viruses often dominate ocean samples numerically, raising the fundamental question of the nature of these viruses. Here we characterize a group of marine dsDNA non-tailed viruses with short 10-kb genomes isolated during a study that quantified the diversity of viruses infecting Vibrionaceae bacteria. These viruses, which we propose to name the Autolykiviridae, represent a novel family within the ancient lineage of double jelly roll (DJR) capsid viruses. Ecologically, members of the Autolykiviridae have a broad host range, killing on average 34 hosts in four Vibrio species, in contrast to tailed viruses which kill on average only two hosts in one species. Biochemical and physical characterization of autolykiviruses reveals multiple virion features that cause systematic loss of DJR viruses in sequencing and culture-based studies, and we describe simple procedural adjustments to recover them. We identify DJR viruses in the genomes of diverse major bacterial and archaeal phyla, and in marine water column and sediment metagenomes, and find that their diversity greatly exceeds the diversity that is currently captured by the three recognized families of such viruses. Overall, these data suggest that viruses of the non-tailed dsDNA DJR lineage are important but often overlooked predators of bacteria and archaea that impose fundamentally different predation and gene transfer regimes on microbial systems than on tailed viruses, which form the basis of all environmental models of bacteria-virus interactions.}, } @article {pmid29364875, year = {2018}, author = {Calo, E and Gu, B and Bowen, ME and Aryan, F and Zalc, A and Liang, J and Flynn, RA and Swigut, T and Chang, HY and Attardi, LD and Wysocka, J}, title = {Tissue-selective effects of nucleolar stress and rDNA damage in developmental disorders.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {112-117}, pmid = {29364875}, issn = {1476-4687}, support = {T32 CA009302/CA/NCI NIH HHS/United States ; R01 GM112720/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R35 CA197591/CA/NCI NIH HHS/United States ; P50 HG007735/HG/NHGRI NIH HHS/United States ; R01 ES023168/ES/NIEHS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Benzothiazoles/pharmacology ; Cell Nucleolus/drug effects/genetics/*metabolism/*pathology ; Cell Nucleus/drug effects/metabolism/pathology ; Chromatin/metabolism ; DEAD-box RNA Helicases/deficiency/genetics/metabolism ; *DNA Damage ; DNA, Ribosomal/genetics/*metabolism ; DNA-Directed RNA Polymerases/deficiency ; Embryonic Stem Cells/cytology/metabolism ; HeLa Cells ; Humans ; Mandibulofacial Dysostosis/embryology/*genetics/*pathology ; Mice ; Naphthyridines/pharmacology ; Neural Crest/enzymology/pathology ; Nuclear Proteins/deficiency/genetics/metabolism ; Organ Specificity ; Phenotype ; Phosphoproteins/deficiency/genetics/metabolism ; Protein Transport/drug effects ; RNA Helicases/metabolism ; RNA Polymerase I/antagonists & inhibitors ; RNA, Ribosomal/biosynthesis/genetics/metabolism ; Ribosomal Proteins/biosynthesis/genetics ; Ribosomes/genetics/metabolism ; Skull/pathology ; *Stress, Physiological/drug effects ; Tumor Suppressor Protein p53/metabolism ; Xenopus ; Zebrafish/embryology ; Zebrafish Proteins/deficiency ; }, abstract = {Many craniofacial disorders are caused by heterozygous mutations in general regulators of housekeeping cellular functions such as transcription or ribosome biogenesis. Although it is understood that many of these malformations are a consequence of defects in cranial neural crest cells, a cell type that gives rise to most of the facial structures during embryogenesis, the mechanism underlying cell-type selectivity of these defects remains largely unknown. By exploring molecular functions of DDX21, a DEAD-box RNA helicase involved in control of both RNA polymerase (Pol) I- and II-dependent transcriptional arms of ribosome biogenesis, we uncovered a previously unappreciated mechanism linking nucleolar dysfunction, ribosomal DNA (rDNA) damage, and craniofacial malformations. Here we demonstrate that genetic perturbations associated with Treacher Collins syndrome, a craniofacial disorder caused by heterozygous mutations in components of the Pol I transcriptional machinery or its cofactor TCOF1 (ref. 1), lead to relocalization of DDX21 from the nucleolus to the nucleoplasm, its loss from the chromatin targets, as well as inhibition of rRNA processing and downregulation of ribosomal protein gene transcription. These effects are cell-type-selective, cell-autonomous, and involve activation of p53 tumour-suppressor protein. We further show that cranial neural crest cells are sensitized to p53-mediated apoptosis, but blocking DDX21 loss from the nucleolus and chromatin rescues both the susceptibility to apoptosis and the craniofacial phenotypes associated with Treacher Collins syndrome. This mechanism is not restricted to cranial neural crest cells, as blood formation is also hypersensitive to loss of DDX21 functions. Accordingly, ribosomal gene perturbations associated with Diamond-Blackfan anaemia disrupt DDX21 localization. At the molecular level, we demonstrate that impaired rRNA synthesis elicits a DNA damage response, and that rDNA damage results in tissue-selective and dosage-dependent effects on craniofacial development. Taken together, our findings illustrate how disruption in general regulators that compromise nucleolar homeostasis can result in tissue-selective malformations.}, } @article {pmid29364874, year = {2018}, author = {Wilson, AM and Hubel, TY and Wilshin, SD and Lowe, JC and Lorenc, M and Dewhirst, OP and Bartlam-Brooks, HLA and Diack, R and Bennitt, E and Golabek, KA and Woledge, RC and McNutt, JW and Curtin, NA and West, TG}, title = {Biomechanics of predator-prey arms race in lion, zebra, cheetah and impala.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {183-188}, pmid = {29364874}, issn = {1476-4687}, support = {BB/J018007/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Acceleration ; Acinonyx/*psychology ; Animals ; Botswana ; Equidae/*physiology ; Female ; Lions/*physiology ; Male ; Muscle, Skeletal/physiology ; Predatory Behavior/*physiology ; Ruminants/*physiology ; Running/physiology ; }, abstract = {The fastest and most manoeuvrable terrestrial animals are found in savannah habitats, where predators chase and capture running prey. Hunt outcome and success rate are critical to survival, so both predator and prey should evolve to be faster and/or more manoeuvrable. Here we compare locomotor characteristics in two pursuit predator-prey pairs, lion-zebra and cheetah-impala, in their natural savannah habitat in Botswana. We show that although cheetahs and impalas were universally more athletic than lions and zebras in terms of speed, acceleration and turning, within each predator-prey pair, the predators had 20% higher muscle fibre power than prey, 37% greater acceleration and 72% greater deceleration capacity than their prey. We simulated hunt dynamics with these data and showed that hunts at lower speeds enable prey to use their maximum manoeuvring capacity and favour prey survival, and that the predator needs to be more athletic than its prey to sustain a viable success rate.}, } @article {pmid29364873, year = {2018}, author = {Hu, W and Lum, GZ and Mastrangeli, M and Sitti, M}, title = {Small-scale soft-bodied robot with multimodal locomotion.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {81-85}, doi = {10.1038/nature25443}, pmid = {29364873}, issn = {1476-4687}, mesh = {Biomimetics/*methods ; Elasticity ; *Equipment Design ; *Locomotion ; Robotics/*instrumentation ; Rotation ; Swimming ; Walking ; }, abstract = {Untethered small-scale (from several millimetres down to a few micrometres in all dimensions) robots that can non-invasively access confined, enclosed spaces may enable applications in microfactories such as the construction of tissue scaffolds by robotic assembly, in bioengineering such as single-cell manipulation and biosensing, and in healthcare such as targeted drug delivery and minimally invasive surgery. Existing small-scale robots, however, have very limited mobility because they are unable to negotiate obstacles and changes in texture or material in unstructured environments. Of these small-scale robots, soft robots have greater potential to realize high mobility via multimodal locomotion, because such machines have higher degrees of freedom than their rigid counterparts. Here we demonstrate magneto-elastic soft millimetre-scale robots that can swim inside and on the surface of liquids, climb liquid menisci, roll and walk on solid surfaces, jump over obstacles, and crawl within narrow tunnels. These robots can transit reversibly between different liquid and solid terrains, as well as switch between locomotive modes. They can additionally execute pick-and-place and cargo-release tasks. We also present theoretical models to explain how the robots move. Like the large-scale robots that can be used to study locomotion, these soft small-scale robots could be used to study soft-bodied locomotion produced by small organisms.}, } @article {pmid29364872, year = {2018}, author = {Nowoshilow, S and Schloissnig, S and Fei, JF and Dahl, A and Pang, AWC and Pippel, M and Winkler, S and Hastie, AR and Young, G and Roscito, JG and Falcon, F and Knapp, D and Powell, S and Cruz, A and Cao, H and Habermann, B and Hiller, M and Tanaka, EM and Myers, EW}, title = {The axolotl genome and the evolution of key tissue formation regulators.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {50-55}, doi = {10.1038/nature25458}, pmid = {29364872}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Ambystoma mexicanum/*genetics ; Animals ; DNA, Intergenic/genetics ; *Evolution, Molecular ; Genes, Essential/genetics ; Genome/*genetics ; *Genomics ; Homeodomain Proteins/genetics ; Introns/genetics ; Male ; Mice ; PAX3 Transcription Factor/genetics ; PAX7 Transcription Factor/genetics ; Picea/genetics ; Pinus/genetics ; Regeneration/genetics ; Retroelements/genetics ; Terminal Repeat Sequences/genetics ; }, abstract = {Salamanders serve as important tetrapod models for developmental, regeneration and evolutionary studies. An extensive molecular toolkit makes the Mexican axolotl (Ambystoma mexicanum) a key representative salamander for molecular investigations. Here we report the sequencing and assembly of the 32-gigabase-pair axolotl genome using an approach that combined long-read sequencing, optical mapping and development of a new genome assembler (MARVEL). We observed a size expansion of introns and intergenic regions, largely attributable to multiplication of long terminal repeat retroelements. We provide evidence that intron size in developmental genes is under constraint and that species-restricted genes may contribute to limb regeneration. The axolotl genome assembly does not contain the essential developmental gene Pax3. However, mutation of the axolotl Pax3 paralogue Pax7 resulted in an axolotl phenotype that was similar to those seen in Pax3-/- and Pax7-/- mutant mice. The axolotl genome provides a rich biological resource for developmental and evolutionary studies.}, } @article {pmid29364871, year = {2018}, author = {Grohme, MA and Schloissnig, S and Rozanski, A and Pippel, M and Young, GR and Winkler, S and Brandl, H and Henry, I and Dahl, A and Powell, S and Hiller, M and Myers, E and Rink, JC}, title = {The genome of Schmidtea mediterranea and the evolution of core cellular mechanisms.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {56-61}, pmid = {29364871}, issn = {1476-4687}, support = {FC001162//Medical Research Council/United Kingdom ; FC001162//Cancer Research UK/United Kingdom ; 649024//European Research Council/International ; FC001162//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Cycle Proteins/deficiency ; *Evolution, Molecular ; Genome/*genetics ; Genomics ; M Phase Cell Cycle Checkpoints/genetics/physiology ; Mad2 Proteins/deficiency ; Planarians/*cytology/*genetics/physiology ; Regeneration/genetics ; Reproduction, Asexual/genetics ; Retroelements/genetics ; }, abstract = {The planarian Schmidtea mediterranea is an important model for stem cell research and regeneration, but adequate genome resources for this species have been lacking. Here we report a highly contiguous genome assembly of S. mediterranea, using long-read sequencing and a de novo assembler (MARVEL) enhanced for low-complexity reads. The S. mediterranea genome is highly polymorphic and repetitive, and harbours a novel class of giant retroelements. Furthermore, the genome assembly lacks a number of highly conserved genes, including critical components of the mitotic spindle assembly checkpoint, but planarians maintain checkpoint function. Our genome assembly provides a key model system resource that will be useful for studying regeneration and the evolutionary plasticity of core cell biological mechanisms.}, } @article {pmid29364870, year = {2018}, author = {McLeod, AF and Reiter, M and Kuiper, R and Klaassen, PD and Evans, CJ}, title = {A parsec-scale optical jet from a massive young star in the Large Magellanic Cloud.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {334-336}, doi = {10.1038/nature25189}, pmid = {29364870}, issn = {1476-4687}, abstract = {Highly collimated parsec-scale jets, which are generally linked to the presence of an accretion disk, are commonly observed in low-mass young stellar objects. In the past two decades, a few of these jets have been directly (or indirectly) observed from higher-mass (larger than eight solar masses) young stellar objects, adding to the growing evidence that disk-mediated accretion also occurs in high-mass stars, the formation mechanism of which is still poorly understood. Of the observed jets from massive young stars, none is in the optical regime (massive young stars are typically highly obscured by their natal material), and none is found outside of the Milky Way. Here we report observations of HH 1177, an optical ionized jet that originates from a massive young stellar object located in the Large Magellanic Cloud. The jet is highly collimated over its entire measured length of at least ten parsecs and has a bipolar geometry. The presence of a jet indicates ongoing, disk-mediated accretion and, together with the high degree of collimation, implies that this system is probably formed through a scaled-up version of the formation mechanism of low-mass stars. We conclude that the physics that govern jet launching and collimation is independent of stellar mass.}, } @article {pmid29364869, year = {2018}, author = {Wood, RA and Bauza, M and Krupic, J and Burton, S and Delekate, A and Chan, D and O'Keefe, J}, title = {The honeycomb maze provides a novel test to study hippocampal-dependent spatial navigation.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {102-105}, doi = {10.1038/nature25433}, pmid = {29364869}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; MR/M018067/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Electrophysiology/instrumentation ; Entorhinal Cortex/pathology/physiopathology/surgery ; *Goals ; Hippocampus/pathology/*physiology/physiopathology/surgery ; Male ; Maze Learning/*physiology ; Rats ; Single-Cell Analysis/instrumentation ; Spatial Navigation/*physiology ; }, abstract = {Here we describe the honeycomb maze, a behavioural paradigm for the study of spatial navigation in rats. The maze consists of 37 platforms that can be raised or lowered independently. Place navigation requires an animal to go to a goal platform from any of several start platforms via a series of sequential choices. For each, the animal is confined to a raised platform and allowed to choose between two of the six adjacent platforms, the correct one being the platform with the smallest angle to the goal-heading direction. Rats learn rapidly and their choices are influenced by three factors: the angle between the two choice platforms, the distance from the goal, and the angle between the correct platform and the direction of the goal. Rats with hippocampal damage are impaired in learning and their performance is affected by all three factors. The honeycomb maze represents a marked improvement over current spatial navigation tests, such as the Morris water maze, because it controls the choices of the animal at each point in the maze, provides the ability to assess knowledge of the goal direction from any location, enables the identification of factors influencing task performance and provides the possibility for concomitant single-cell recording.}, } @article {pmid29364868, year = {2018}, author = {Wong, YC and Ysselstein, D and Krainc, D}, title = {Mitochondria-lysosome contacts regulate mitochondrial fission via RAB7 GTP hydrolysis.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {382-386}, pmid = {29364868}, issn = {1476-4687}, support = {1S10OD016342-01/NH/NIH HHS/United States ; T32 NS041234/NS/NINDS NIH HHS/United States ; S10 OD016342/OD/NIH HHS/United States ; F32 NS101778/NS/NINDS NIH HHS/United States ; R01 NS076054/NS/NINDS NIH HHS/United States ; P30 CA060553/CA/NCI NIH HHS/United States ; S10 RR031680/RR/NCRR NIH HHS/United States ; }, mesh = {Binding Sites ; GTPase-Activating Proteins/metabolism ; Guanosine Triphosphate/metabolism ; HeLa Cells ; Humans ; Hydrolysis ; Intracellular Membranes/metabolism ; Lysosomes/*metabolism ; Membrane Proteins/metabolism ; Mitochondria/*metabolism ; Mitochondrial Degradation ; *Mitochondrial Dynamics ; Mitochondrial Proteins/metabolism ; rab GTP-Binding Proteins/*metabolism ; }, abstract = {Both mitochondria and lysosomes are essential for maintaining cellular homeostasis, and dysfunction of both organelles has been observed in multiple diseases. Mitochondria are highly dynamic and undergo fission and fusion to maintain a functional mitochondrial network, which drives cellular metabolism. Lysosomes similarly undergo constant dynamic regulation by the RAB7 GTPase, which cycles from an active GTP-bound state into an inactive GDP-bound state upon GTP hydrolysis. Here we have identified the formation and regulation of mitochondria-lysosome membrane contact sites using electron microscopy, structured illumination microscopy and high spatial and temporal resolution confocal live cell imaging. Mitochondria-lysosome contacts formed dynamically in healthy untreated cells and were distinct from damaged mitochondria that were targeted into lysosomes for degradation. Contact formation was promoted by active GTP-bound lysosomal RAB7, and contact untethering was mediated by recruitment of the RAB7 GTPase-activating protein TBC1D15 to mitochondria by FIS1 to drive RAB7 GTP hydrolysis and thereby release contacts. Functionally, lysosomal contacts mark sites of mitochondrial fission, allowing regulation of mitochondrial networks by lysosomes, whereas conversely, mitochondrial contacts regulate lysosomal RAB7 hydrolysis via TBC1D15. Mitochondria-lysosome contacts thus allow bidirectional regulation of mitochondrial and lysosomal dynamics, and may explain the dysfunction observed in both organelles in various human diseases.}, } @article {pmid29364867, year = {2018}, author = {Mueller, S and Engleitner, T and Maresch, R and Zukowska, M and Lange, S and Kaltenbacher, T and Konukiewitz, B and Öllinger, R and Zwiebel, M and Strong, A and Yen, HY and Banerjee, R and Louzada, S and Fu, B and Seidler, B and Götzfried, J and Schuck, K and Hassan, Z and Arbeiter, A and Schönhuber, N and Klein, S and Veltkamp, C and Friedrich, M and Rad, L and Barenboim, M and Ziegenhain, C and Hess, J and Dovey, OM and Eser, S and Parekh, S and Constantino-Casas, F and de la Rosa, J and Sierra, MI and Fraga, M and Mayerle, J and Klöppel, G and Cadiñanos, J and Liu, P and Vassiliou, G and Weichert, W and Steiger, K and Enard, W and Schmid, RM and Yang, F and Unger, K and Schneider, G and Varela, I and Bradley, A and Saur, D and Rad, R}, title = {Evolutionary routes and KRAS dosage define pancreatic cancer phenotypes.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {62-68}, pmid = {29364867}, issn = {1476-4687}, support = {648521//European Research Council/International ; }, mesh = {Adaptor Proteins, Signal Transducing/genetics ; Alleles ; Animals ; Carcinogenesis/genetics ; Carcinoma, Pancreatic Ductal/*genetics/*pathology ; Cyclin-Dependent Kinase Inhibitor p16/genetics ; Disease Progression ; *Evolution, Molecular ; Female ; *Gene Dosage ; Genes, myc ; Genes, p53 ; Humans ; Male ; Mice ; Mutation ; NF-kappa B p52 Subunit/genetics ; Neoplasm Metastasis/genetics ; Nuclear Proteins/genetics ; Pancreatic Neoplasms/*genetics/*pathology ; Phenotype ; Phosphoproteins/genetics ; Proto-Oncogene Proteins p21(ras)/*genetics ; Transcription Factors/genetics ; Transcriptome/genetics ; Transforming Growth Factor beta1/genetics ; }, abstract = {The poor correlation of mutational landscapes with phenotypes limits our understanding of the pathogenesis and metastasis of pancreatic ductal adenocarcinoma (PDAC). Here we show that oncogenic dosage-variation has a critical role in PDAC biology and phenotypic diversification. We find an increase in gene dosage of mutant KRAS in human PDAC precursors, which drives both early tumorigenesis and metastasis and thus rationalizes early PDAC dissemination. To overcome the limitations posed to gene dosage studies by the stromal richness of PDAC, we have developed large cell culture resources of metastatic mouse PDAC. Integration of cell culture genomes, transcriptomes and tumour phenotypes with functional studies and human data reveals additional widespread effects of oncogenic dosage variation on cell morphology and plasticity, histopathology and clinical outcome, with the highest KrasMUT levels underlying aggressive undifferentiated phenotypes. We also identify alternative oncogenic gains (Myc, Yap1 or Nfkb2), which collaborate with heterozygous KrasMUT in driving tumorigenesis, but have lower metastatic potential. Mechanistically, different oncogenic gains and dosages evolve along distinct evolutionary routes, licensed by defined allelic states and/or combinations of hallmark tumour suppressor alterations (Cdkn2a, Trp53, Tgfβ-pathway). Thus, evolutionary constraints and contingencies direct oncogenic dosage gain and variation along defined routes to drive the early progression of PDAC and shape its downstream biology. Our study uncovers universal principles of Ras-driven oncogenesis that have potential relevance beyond pancreatic cancer.}, } @article {pmid29364288, year = {2018}, author = {Pașca, SP}, title = {The rise of three-dimensional human brain cultures.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {437-445}, pmid = {29364288}, issn = {1476-4687}, mesh = {Biological Evolution ; Brain/*cytology/embryology/growth & development ; Cell Differentiation ; Humans ; Models, Biological ; Neurons/cytology ; Organ Culture Techniques/*methods/standards ; Organogenesis ; Pluripotent Stem Cells/cytology ; Quality Control ; }, abstract = {Pluripotent stem cells show a remarkable ability to self-organize and differentiate in vitro in three-dimensional aggregates, known as organoids or organ spheroids, and to recapitulate aspects of human brain development and function. Region-specific 3D brain cultures can be derived from any individual and assembled to model complex cell-cell interactions and to generate circuits in human brain assembloids. Here I discuss how this approach can be used to understand unique features of the human brain and to gain insights into neuropsychiatric disorders. In addition, I consider the challenges faced by researchers in further improving and developing methods to probe and manipulate patient-derived 3D brain cultures.}, } @article {pmid29364287, year = {2018}, author = {Herbst, RS and Morgensztern, D and Boshoff, C}, title = {The biology and management of non-small cell lung cancer.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {446-454}, pmid = {29364287}, issn = {1476-4687}, mesh = {Carcinoma, Non-Small-Cell Lung/genetics/*metabolism/pathology/*therapy ; Clinical Trials as Topic ; Humans ; Immunotherapy ; Lung Neoplasms/genetics/*metabolism/pathology/*therapy ; Molecular Targeted Therapy ; Precision Medicine ; Survival Rate ; Tumor Microenvironment/genetics ; }, abstract = {Important advancements in the treatment of non-small cell lung cancer (NSCLC) have been achieved over the past two decades, increasing our understanding of the disease biology and mechanisms of tumour progression, and advancing early detection and multimodal care. The use of small molecule tyrosine kinase inhibitors and immunotherapy has led to unprecedented survival benefits in selected patients. However, the overall cure and survival rates for NSCLC remain low, particularly in metastatic disease. Therefore, continued research into new drugs and combination therapies is required to expand the clinical benefit to a broader patient population and to improve outcomes in NSCLC.}, } @article {pmid29364286, year = {2018}, author = {Chen, YE and Fischbach, MA and Belkaid, Y}, title = {Skin microbiota-host interactions.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {427-436}, pmid = {29364286}, issn = {1476-4687}, support = {DP1 DK113598/DK/NIDDK NIH HHS/United States ; R01 DK110174/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Health ; Host-Pathogen Interactions/genetics/immunology/*physiology ; Humans ; Microbial Interactions ; Microbiota/*immunology/*physiology ; Skin/chemistry/*immunology/*microbiology ; Symbiosis ; }, abstract = {The skin is a complex and dynamic ecosystem that is inhabited by bacteria, archaea, fungi and viruses. These microbes-collectively referred to as the skin microbiota-are fundamental to skin physiology and immunity. Interactions between skin microbes and the host can fall anywhere along the continuum between mutualism and pathogenicity. In this Review, we highlight how host-microbe interactions depend heavily on context, including the state of immune activation, host genetic predisposition, barrier status, microbe localization, and microbe-microbe interactions. We focus on how context shapes the complex dialogue between skin microbes and the host, and the consequences of this dialogue for health and disease.}, } @article {pmid29364285, year = {2018}, author = {Laurenti, E and Göttgens, B}, title = {From haematopoietic stem cells to complex differentiation landscapes.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {418-426}, pmid = {29364285}, issn = {1476-4687}, support = {G0900951//Medical Research Council/United Kingdom ; MR/M008975/1//Medical Research Council/United Kingdom ; R24 DK106766/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, mesh = {Adult Stem Cells/cytology ; Animals ; Cell Cycle ; Cell Lineage ; Cell Self Renewal ; Gene Expression Profiling ; Hematologic Diseases/therapy ; *Hematopoiesis/genetics ; Hematopoietic Stem Cells/*cytology ; Humans ; Multipotent Stem Cells/cytology ; Single-Cell Analysis ; }, abstract = {The development of mature blood cells from haematopoietic stem cells has long served as a model for stem-cell research, with the haematopoietic differentiation tree being widely used as a model for the maintenance of hierarchically organized tissues. Recent results and new technologies have challenged the demarcations between stem and progenitor cell populations, the timing of cell-fate choices and the contribution of stem and multipotent progenitor cells to the maintenance of steady-state blood production. These evolving views of haematopoiesis have broad implications for our understanding of the functions of adult stem cells, as well as the development of new therapies for malignant and non-malignant haematopoietic diseases.}, } @article {pmid29363614, year = {2018}, author = {Beans, C}, title = {Science and Culture: Painting with invasive pigments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {627-629}, doi = {10.1073/pnas.1721721115}, pmid = {29363614}, issn = {1091-6490}, } @article {pmid29363607, year = {2018}, author = {Lund, J}, title = {Weighing the evidence for a body mass-regulating gravitostat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1334}, pmid = {29363607}, issn = {1091-6490}, mesh = {*Body Weight ; Humans ; }, } @article {pmid29363606, year = {2018}, author = {Ohlsson, C and Jansson, JO}, title = {Reply to Lund: Where does the gravitostat fit in?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1335}, pmid = {29363606}, issn = {1091-6490}, mesh = {*Tomography, X-Ray Computed ; }, } @article {pmid29363605, year = {2018}, author = {Safra, L and Baumard, N and Chevallier, C}, title = {No strong evidence that authoritarian attitudes are driven by a lack of control.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1076-E1077}, pmid = {29363605}, issn = {1091-6490}, mesh = {*Attitude ; *Parenting ; }, } @article {pmid29363604, year = {2018}, author = {Kakkar, H and Sivanathan, N}, title = {Reply to Safra et al.: Lack of theoretical rationale and selective analysis does not imply no strong evidence.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1078-E1079}, pmid = {29363604}, issn = {1091-6490}, } @article {pmid29363603, year = {2018}, author = {Gruters, KG and Murphy, DLK and Jenson, CD and Smith, DW and Shera, CA and Groh, JM}, title = {The eardrums move when the eyes move: A multisensory effect on the mechanics of hearing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1309-E1318}, pmid = {29363603}, issn = {1091-6490}, support = {R01 DC003687/DC/NIDCD NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Animals ; Auditory Pathways/*physiology ; Brain/*physiology ; Female ; Hearing/*physiology ; Humans ; Macaca mulatta ; Male ; Photic Stimulation ; Saccades/*physiology ; Tympanic Membrane/*physiology ; Young Adult ; }, abstract = {Interactions between sensory pathways such as the visual and auditory systems are known to occur in the brain, but where they first occur is uncertain. Here, we show a multimodal interaction evident at the eardrum. Ear canal microphone measurements in humans (n = 19 ears in 16 subjects) and monkeys (n = 5 ears in three subjects) performing a saccadic eye movement task to visual targets indicated that the eardrum moves in conjunction with the eye movement. The eardrum motion was oscillatory and began as early as 10 ms before saccade onset in humans or with saccade onset in monkeys. These eardrum movements, which we dub eye movement-related eardrum oscillations (EMREOs), occurred in the absence of a sound stimulus. The amplitude and phase of the EMREOs depended on the direction and horizontal amplitude of the saccade. They lasted throughout the saccade and well into subsequent periods of steady fixation. We discuss the possibility that the mechanisms underlying EMREOs create eye movement-related binaural cues that may aid the brain in evaluating the relationship between visual and auditory stimulus locations as the eyes move.}, } @article {pmid29363602, year = {2018}, author = {Ram, Y and Liberman, U and Feldman, MW}, title = {Evolution of vertical and oblique transmission under fluctuating selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1174-E1183}, pmid = {29363602}, issn = {1091-6490}, mesh = {Adaptation, Physiological ; *Biological Evolution ; *Environment ; *Genetics, Population ; Humans ; *Models, Genetic ; Mutation ; Phenotype ; *Selection, Genetic ; }, abstract = {The evolution and maintenance of social learning, in competition with individual learning, under fluctuating selection have been well-studied in the theory of cultural evolution. Here, we study competition between vertical and oblique cultural transmission of a dichotomous phenotype under constant, periodically cycling, and randomly fluctuating selection. Conditions are derived for the existence of a stable polymorphism in a periodically cycling selection regime. Under such a selection regime, the fate of a genetic modifier of the rate of vertical transmission depends on the length of the cycle and the strength of selection. In general, the evolutionarily stable rate of vertical transmission differs markedly from the rate that maximizes the geometric mean fitness of the population. The evolution of rules of transmission has dramatically different dynamics from the more frequently studied modifiers of recombination, mutation, or migration.}, } @article {pmid29363601, year = {2018}, author = {Burger, JR and Fristoe, TS}, title = {Hunter-gatherer populations inform modern ecology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1137-1139}, pmid = {29363601}, issn = {1091-6490}, mesh = {*Ecology ; Humans ; *Population Groups ; }, } @article {pmid29363600, year = {2018}, author = {Sato, Y and Kasahara, S and Taniguchi, T and Xing, X and Kasahara, Y and Tokiwa, Y and Yamakawa, Y and Kontani, H and Shibauchi, T and Matsuda, Y}, title = {Abrupt change of the superconducting gap structure at the nematic critical point in FeSe1-xSx.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1227-1231}, pmid = {29363600}, issn = {1091-6490}, abstract = {The emergence of the nematic electronic state that breaks rotational symmetry is one of the most fascinating properties of the iron-based superconductors, and has relevance to cuprates as well. FeSe has a unique ground state in which superconductivity coexists with a nematic order without long-range magnetic ordering, providing a significant opportunity to investigate the role of nematicity in the superconducting pairing interaction. Here, to reveal how the superconducting gap evolves with nematicity, we measure the thermal conductivity and specific heat of FeSe1 - x S x , in which the nematicity is suppressed by isoelectronic sulfur substitution and a nematic critical point (NCP) appears at [Formula: see text] We find that, in the whole nematic regime ([Formula: see text]), the field dependence of two quantities consistently shows two-gap behavior; one gap is small but highly anisotropic with deep minima or line nodes, and the other is larger and more isotropic. In stark contrast, in the tetragonal regime ([Formula: see text]), the larger gap becomes strongly anisotropic, demonstrating an abrupt change in the superconducting gap structure at the NCP. Near the NCP, charge fluctuations of [Formula: see text] and [Formula: see text] orbitals are enhanced equally in the tetragonal side, whereas they develop differently in the orthorhombic side. Our observation therefore directly implies that the orbital-dependent nature of the nematic fluctuations has a strong impact on the superconducting gap structure and hence on the pairing interaction.}, } @article {pmid29363599, year = {2018}, author = {Marturano-Kruik, A and Nava, MM and Yeager, K and Chramiec, A and Hao, L and Robinson, S and Guo, E and Raimondi, MT and Vunjak-Novakovic, G}, title = {Human bone perivascular niche-on-a-chip for studying metastatic colonization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1256-1261}, pmid = {29363599}, issn = {1091-6490}, support = {UH2 EB017103/EB/NIBIB NIH HHS/United States ; 646990//European Research Council/International ; UG3 EB025765/EB/NIBIB NIH HHS/United States ; UH3 EB017103/EB/NIBIB NIH HHS/United States ; P41 EB002520/EB/NIBIB NIH HHS/United States ; }, mesh = {Bone Matrix/pathology ; Bone Neoplasms/drug therapy/pathology/*secondary ; Breast Neoplasms/drug therapy/*pathology ; Cell Line, Tumor ; Coculture Techniques/*instrumentation/methods ; Drug Resistance, Neoplasm ; Female ; Humans ; *Lab-On-A-Chip Devices ; Mesenchymal Stem Cells/cytology ; Oxygen ; Perfusion ; Tissue Scaffolds ; }, abstract = {Eight out of 10 breast cancer patients die within 5 years after the primary tumor has spread to the bones. Tumor cells disseminated from the breast roam the vasculature, colonizing perivascular niches around blood capillaries. Slow flows support the niche maintenance by driving the oxygen, nutrients, and signaling factors from the blood into the interstitial tissue, while extracellular matrix, endothelial cells, and mesenchymal stem cells regulate metastatic homing. Here, we show the feasibility of developing a perfused bone perivascular niche-on-a-chip to investigate the progression and drug resistance of breast cancer cells colonizing the bone. The model is a functional human triculture with stable vascular networks within a 3D native bone matrix cultured on a microfluidic chip. Providing the niche-on-a-chip with controlled flow velocities, shear stresses, and oxygen gradients, we established a long-lasting, self-assembled vascular network without supplementation of angiogenic factors. We further show that human bone marrow-derived mesenchymal stem cells, which have undergone phenotypical transition toward perivascular cell lineages, support the formation of capillary-like structures lining the vascular lumen. Finally, breast cancer cells exposed to interstitial flow within the bone perivascular niche-on-a-chip persist in a slow-proliferative state associated with increased drug resistance. We propose that the bone perivascular niche-on-a-chip with interstitial flow promotes the formation of stable vasculature and mediates cancer cell colonization.}, } @article {pmid29363598, year = {2018}, author = {Bouton, S and Chambon, V and Tyrand, R and Guggisberg, AG and Seeck, M and Karkar, S and van de Ville, D and Giraud, AL}, title = {Focal versus distributed temporal cortex activity for speech sound category assignment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1299-E1308}, pmid = {29363598}, issn = {1091-6490}, mesh = {Acoustic Stimulation ; Adult ; Aged ; Brain Mapping ; Case-Control Studies ; Epilepsy/*physiopathology ; Female ; Humans ; Magnetic Resonance Imaging ; Magnetoencephalography ; Male ; *Phonetics ; Speech Perception/*physiology ; Temporal Lobe/*physiology ; Young Adult ; }, abstract = {Percepts and words can be decoded from distributed neural activity measures. However, the existence of widespread representations might conflict with the more classical notions of hierarchical processing and efficient coding, which are especially relevant in speech processing. Using fMRI and magnetoencephalography during syllable identification, we show that sensory and decisional activity colocalize to a restricted part of the posterior superior temporal gyrus (pSTG). Next, using intracortical recordings, we demonstrate that early and focal neural activity in this region distinguishes correct from incorrect decisions and can be machine-decoded to classify syllables. Crucially, significant machine decoding was possible from neuronal activity sampled across different regions of the temporal and frontal lobes, despite weak or absent sensory or decision-related responses. These findings show that speech-sound categorization relies on an efficient readout of focal pSTG neural activity, while more distributed activity patterns, although classifiable by machine learning, instead reflect collateral processes of sensory perception and decision.}, } @article {pmid29363597, year = {2018}, author = {Liao, DA and Ghazanfar, AA}, title = {Ephemeral connections for reaching and grasping.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1143-1144}, pmid = {29363597}, issn = {1091-6490}, mesh = {*Hand Strength ; Movement ; *Psychomotor Performance ; }, } @article {pmid29363596, year = {2018}, author = {Landrein, B and Formosa-Jordan, P and Malivert, A and Schuster, C and Melnyk, CW and Yang, W and Turnbull, C and Meyerowitz, EM and Locke, JCW and Jönsson, H}, title = {Nitrate modulates stem cell dynamics in Arabidopsis shoot meristems through cytokinins.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1382-1387}, pmid = {29363596}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/*cytology/genetics/metabolism ; Arabidopsis Proteins/genetics/metabolism ; Cytokinins/*metabolism ; Flowers/physiology ; Gene Expression Regulation, Plant ; Homeodomain Proteins/metabolism ; Meristem/*cytology/metabolism/physiology ; Nitrates/*metabolism ; Plant Cells/metabolism ; Plant Shoots/*cytology/metabolism ; Plant Stems/cytology/metabolism ; Plants, Genetically Modified ; Signal Transduction ; Soil/chemistry ; }, abstract = {The shoot apical meristem (SAM) is responsible for the generation of all the aerial parts of plants. Given its critical role, dynamical changes in SAM activity should play a central role in the adaptation of plant architecture to the environment. Using quantitative microscopy, grafting experiments, and genetic perturbations, we connect the plant environment to the SAM by describing the molecular mechanism by which cytokinins signal the level of nutrient availability to the SAM. We show that a systemic signal of cytokinin precursors mediates the adaptation of SAM size and organogenesis rate to the availability of mineral nutrients by modulating the expression of WUSCHEL, a key regulator of stem cell homeostasis. In time-lapse experiments, we further show that this mechanism allows meristems to adapt to rapid changes in nitrate concentration, and thereby modulate their rate of organ production to the availability of mineral nutrients within a few days. Our work sheds light on the role of the stem cell regulatory network by showing that it not only maintains meristem homeostasis but also allows plants to adapt to rapid changes in the environment.}, } @article {pmid29363595, year = {2018}, author = {Nair, J and Klaassen, AL and Arato, J and Vyssotski, AL and Harvey, M and Rainer, G}, title = {Basal forebrain contributes to default mode network regulation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1352-1357}, pmid = {29363595}, issn = {1091-6490}, mesh = {Animals ; Basal Forebrain/*physiology ; Behavior, Animal ; Exploratory Behavior/*physiology ; Gyrus Cinguli/physiology ; Locomotion ; Male ; Nerve Net ; Rats, Long-Evans ; Task Performance and Analysis ; Wakefulness ; }, abstract = {The default mode network (DMN) is a collection of cortical brain regions that is active during states of rest or quiet wakefulness in humans and other mammalian species. A pertinent characteristic of the DMN is a suppression of local field potential gamma activity during cognitive task performance as well as during engagement with external sensory stimuli. Conversely, gamma activity is elevated in the DMN during rest. Here, we document that the rat basal forebrain (BF) exhibits the same pattern of responses, namely pronounced gamma oscillations during quiet wakefulness in the home cage and suppression of this activity during active exploration of an unfamiliar environment. We show that gamma oscillations are localized to the BF and that gamma-band activity in the BF has a directional influence on a hub of the rat DMN, the anterior cingulate cortex, during DMN-dominated brain states. The BF is well known as an ascending, activating, neuromodulatory system involved in wake-sleep regulation, memory formation, and regulation of sensory information processing. Our findings suggest a hitherto undocumented role of the BF as a subcortical node of the DMN, which we speculate may be important for switching between internally and externally directed brain states. We discuss potential BF projection circuits that could underlie its role in DMN regulation and highlight that certain BF nuclei may provide potential target regions for up- or down-regulation of DMN activity that might prove useful for treatment of DMN dysfunction in conditions such as epilepsy or major depressive disorder.}, } @article {pmid29363594, year = {2018}, author = {Rosas-Diaz, T and Zhang, D and Fan, P and Wang, L and Ding, X and Jiang, Y and Jimenez-Gongora, T and Medina-Puche, L and Zhao, X and Feng, Z and Zhang, G and Liu, X and Bejarano, ER and Tan, L and Zhang, H and Zhu, JK and Xing, W and Faulkner, C and Nagawa, S and Lozano-Duran, R}, title = {A virus-targeted plant receptor-like kinase promotes cell-to-cell spread of RNAi.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1388-1393}, pmid = {29363594}, issn = {1091-6490}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Arabidopsis/*genetics/virology ; Arabidopsis Proteins/genetics/*metabolism ; Begomovirus/chemistry ; Host-Pathogen Interactions/genetics ; Plant Cells ; Plants, Genetically Modified ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; *RNA Interference ; Tobacco/genetics ; Viral Proteins/*genetics/metabolism ; }, abstract = {RNA interference (RNAi) in plants can move from cell to cell, allowing for systemic spread of an antiviral immune response. How this cell-to-cell spread of silencing is regulated is currently unknown. Here, we describe that the C4 protein from Tomato yellow leaf curl virus can inhibit the intercellular spread of RNAi. Using this viral protein as a probe, we have identified the receptor-like kinase (RLK) BARELY ANY MERISTEM 1 (BAM1) as a positive regulator of the cell-to-cell movement of RNAi, and determined that BAM1 and its closest homolog, BAM2, play a redundant role in this process. C4 interacts with the intracellular domain of BAM1 and BAM2 at the plasma membrane and plasmodesmata, the cytoplasmic connections between plant cells, interfering with the function of these RLKs in the cell-to-cell spread of RNAi. Our results identify BAM1 as an element required for the cell-to-cell spread of RNAi and highlight that signaling components have been coopted to play multiple functions in plants.}, } @article {pmid29363593, year = {2018}, author = {Campiglio, M and Costé de Bagneaux, P and Ortner, NJ and Tuluc, P and Van Petegem, F and Flucher, BE}, title = {STAC proteins associate to the IQ domain of CaV1.2 and inhibit calcium-dependent inactivation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1376-1381}, pmid = {29363593}, issn = {1091-6490}, mesh = {Amino Acid Motifs ; Animals ; Calcium/*metabolism ; Calcium Channels, L-Type/genetics/*metabolism ; Calmodulin/metabolism ; Green Fluorescent Proteins/genetics/metabolism ; Houseflies ; Humans ; Mice ; Muscle Fibers, Skeletal/cytology ; Nerve Tissue Proteins/genetics/*metabolism ; Patch-Clamp Techniques ; Protein Domains ; *Protein Interaction Domains and Motifs ; Recombinant Proteins/genetics/metabolism ; }, abstract = {The adaptor proteins STAC1, STAC2, and STAC3 represent a newly identified family of regulators of voltage-gated calcium channel (CaV) trafficking and function. The skeletal muscle isoform STAC3 is essential for excitation-contraction coupling and its mutation causes severe muscle disease. Recently, two distinct molecular domains in STAC3 were identified, necessary for its functional interaction with CaV1.1: the C1 domain, which recruits STAC proteins to the calcium channel complex in skeletal muscle triads, and the SH3-1 domain, involved in excitation-contraction coupling. These interaction sites are conserved in the three STAC proteins. However, the molecular domain in CaV1 channels interacting with the STAC C1 domain and the possible role of this interaction in neuronal CaV1 channels remained unknown. Using CaV1.2/2.1 chimeras expressed in dysgenic (CaV1.1-/-) myotubes, we identified the amino acids 1,641-1,668 in the C terminus of CaV1.2 as necessary for association of STAC proteins. This sequence contains the IQ domain and alanine mutagenesis revealed that the amino acids important for STAC association overlap with those making contacts with the C-lobe of calcium-calmodulin (Ca/CaM) and mediating calcium-dependent inactivation of CaV1.2. Indeed, patch-clamp analysis demonstrated that coexpression of either one of the three STAC proteins with CaV1.2 opposed calcium-dependent inactivation, although to different degrees, and that substitution of the CaV1.2 IQ domain with that of CaV2.1, which does not interact with STAC, abolished this effect. These results suggest that STAC proteins associate with the CaV1.2 C terminus at the IQ domain and thus inhibit calcium-dependent feedback regulation of CaV1.2 currents.}, } @article {pmid29363592, year = {2018}, author = {Yaniv, SP and Schuldiner, O}, title = {Pebbled makes ripples: A transcription factor primes glutamatergic but not cholinergic neurons for degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1140-1142}, pmid = {29363592}, issn = {1091-6490}, mesh = {Choline O-Acetyltransferase ; *Cholinergic Neurons ; *Transcription Factors ; }, } @article {pmid29363433, year = {2018}, author = {Wang, X and Lin, P and Ho, JWK}, title = {Discovery of cell-type specific DNA motif grammar in cis-regulatory elements using random Forest.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {929}, pmid = {29363433}, issn = {1471-2164}, mesh = {*Algorithms ; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/classification/genetics ; Computational Biology/*methods ; Gene Expression Regulation, Neoplastic ; Humans ; Neoplasms/classification/*genetics ; *Nucleotide Motifs ; *Regulatory Elements, Transcriptional ; Software ; Transcription Factor 7-Like 2 Protein/classification/genetics ; Tumor Cells, Cultured ; }, abstract = {BACKGROUND: It has been observed that many transcription factors (TFs) can bind to different genomic loci depending on the cell type in which a TF is expressed in, even though the individual TF usually binds to the same core motif in different cell types. How a TF can bind to the genome in such a highly cell-type specific manner, is a critical research question. One hypothesis is that a TF requires co-binding of different TFs in different cell types. If this is the case, it may be possible to observe different combinations of TF motifs - a motif grammar - located at the TF binding sites in different cell types. In this study, we develop a bioinformatics method to systematically identify DNA motifs in TF binding sites across multiple cell types based on published ChIP-seq data, and address two questions: (1) can we build a machine learning classifier to predict cell-type specificity based on motif combinations alone, and (2) can we extract meaningful cell-type specific motif grammars from this classifier model.

RESULTS: We present a Random Forest (RF) based approach to build a multi-class classifier to predict the cell-type specificity of a TF binding site given its motif content. We applied this RF classifier to two published ChIP-seq datasets of TF (TCF7L2 and MAX) across multiple cell types. Using cross-validation, we show that motif combinations alone are indeed predictive of cell types. Furthermore, we present a rule mining approach to extract the most discriminatory rules in the RF classifier, thus allowing us to discover the underlying cell-type specific motif grammar.

CONCLUSIONS: Our bioinformatics analysis supports the hypothesis that combinatorial TF motif patterns are cell-type specific.}, } @article {pmid29363432, year = {2018}, author = {Schönbach, C and Li, J and Ma, L and Horton, P and Sjaugi, MF and Ranganathan, S}, title = {A bioinformatics potpourri.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {920}, pmid = {29363432}, issn = {1471-2164}, mesh = {Animals ; *Computational Biology ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Systems Biology/*methods ; }, abstract = {The 16th International Conference on Bioinformatics (InCoB) was held at Tsinghua University, Shenzhen from September 20 to 22, 2017. The annual conference of the Asia-Pacific Bioinformatics Network featured six keynotes, two invited talks, a panel discussion on big data driven bioinformatics and precision medicine, and 66 oral presentations of accepted research articles or posters. Fifty-seven articles comprising a topic assortment of algorithms, biomolecular networks, cancer and disease informatics, drug-target interactions and drug efficacy, gene regulation and expression, imaging, immunoinformatics, metagenomics, next generation sequencing for genomics and transcriptomics, ontologies, post-translational modification, and structural bioinformatics are the subject of this editorial for the InCoB2017 supplement issues in BMC Genomics, BMC Bioinformatics, BMC Systems Biology and BMC Medical Genomics. New Delhi will be the location of InCoB2018, scheduled for September 26-28, 2018.}, } @article {pmid29363431, year = {2018}, author = {Zhao, Y and Sun, C and Zhao, D and Zhang, Y and You, Y and Jia, X and Yang, J and Wang, L and Wang, J and Fu, H and Kang, Y and Chen, F and Yu, J and Wu, J and Xiao, J}, title = {PGAP-X: extension on pan-genome analysis pipeline.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {36}, pmid = {29363431}, issn = {1471-2164}, mesh = {Chlamydia trachomatis/classification/*genetics ; Computer Graphics ; *Evolution, Molecular ; *Genetic Variation ; *Genome, Bacterial ; High-Throughput Nucleotide Sequencing ; *Software ; Streptococcus pneumoniae/classification/*genetics ; }, abstract = {BACKGROUND: Since PGAP (pan-genome analysis pipeline) was published in 2012, it has been widely employed in bacterial genomics research. Though PGAP has integrated several modules for pan-genomics analysis, how to properly and effectively interpret and visualize the results data is still a challenge.

RESULT: To well present bacterial genomic characteristics, a novel cross-platform software was developed, named PGAP-X. Four kinds of data analysis modules were developed and integrated: whole genome sequences alignment, orthologous genes clustering, pan-genome profile analysis, and genetic variants analysis. The results from these analyses can be directly visualized in PGAP-X. The modules for data visualization in PGAP-X include: comparison of genome structure, gene distribution by conservation, pan-genome profile curve and variation on genic and genomic region. Meanwhile, result data produced by other programs with similar function can be imported to be further analyzed and visualized in PGAP-X. To test the performance of PGAP-X, we comprehensively analyzed 14 Streptococcus pneumonia strains and 14 Chlamydia trachomatis. The results show that, S. pneumonia strains have higher diversity on genome structure and gene contents than C. trachomatis strains. In addition, S. pneumonia strains might have suffered many evolutionary events, such genomic rearrangements, frequent horizontal gene transfer, homologous recombination, and other evolutionary process.

CONCLUSION: Briefly, PGAP-X directly presents the characteristics of bacterial genomic diversity with different visualization methods, which could help us to intuitively understand dynamics and evolution in bacterial genomes. The source code and the pre-complied executable programs are freely available from http://pgapx.ybzhao.com .}, } @article {pmid29363430, year = {2018}, author = {Cao, Y and Cao, R and Huang, Y and Zhou, H and Liu, Y and Li, X and Zhong, W and Hao, P}, title = {A comprehensive study on cellular RNA editing activity in response to infections with different subtypes of influenza a viruses.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {925}, pmid = {29363430}, issn = {1471-2164}, mesh = {Animals ; Birds/*genetics/physiology/virology ; Cells, Cultured ; Computational Biology/*methods ; Epithelial Cells/virology ; Gene Expression Regulation ; Humans ; Influenza A virus/classification/*genetics ; Influenza in Birds/*genetics/virology ; Influenza, Human/*genetics/virology ; RNA Editing/*genetics ; RNA-Binding Proteins/genetics/metabolism ; Virus Replication ; }, abstract = {BACKGROUND: RNA editing is an important mechanism that expands the diversity and complexity of genetic codes. The conversions of adenosine (A) to inosine (I) and cytosine (C) to uridine (U) are two prominent types of RNA editing in animals. The roles of RNA editing events have been implicated in important biological pathways. Cellular RNA editing activity in response to influenza A virus infection has not been fully characterized in human and avian hosts. This study was designed as a big data analysis to investigate the role and response of RNA editing in epithelial cells during the course of infection with various subtypes of influenza A viruses.

RESULTS: Using a bioinformatics pipeline modified from our previous study, we characterized the profiles of A-to-I and C-to-U RNA editing events in human epithelial cells during the course of influenza A virus infection. Our results revealed a striking diversity of A-to-I RNA editing activities in human epithelial cells in responses to different subtypes of influenza A viruses. The infection of H1N1 and H3N2 significantly up-regulated normalized A-to-I RNA editing levels in human epithelial cells, whereas that of H5N1 did not change it and H7N9 infection significantly down-regulated normalized A-to-I editing level in A549 cells. Next, the expression levels of ADAR and APOBEC enzymes responsible for A-to-I and C-to-U RNA editing during the course of virus infection were examined. The increase of A-to-I RNA editing activities in infections with some influenza A viruses (H1N1 and H3N2) is linked to the up-regulation of ADAR1 but not ADAR2. Further, the pattern recognition receptors of human epithelial cells infected with H1N1, H3N2, H5N1 and H7N9 were examined. Variable responsive changes in gene expression were observed with RIG-I like receptors and Toll like receptors. Finally, the effect of influenza A virus infection on cellular RNA editing activity was also analyzed in avian hosts.

CONCLUSION: This work represents the first comprehensive study of cellular RNA editing activity in response to different influenza A virus infections in human and avian hosts, highlighting the critical role of RNA editing in innate immune response and the pathogenicity of different subtypes of influenza A viruses.}, } @article {pmid29363429, year = {2018}, author = {Osato, N}, title = {Characteristics of functional enrichment and gene expression level of human putative transcriptional target genes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {957}, pmid = {29363429}, issn = {1471-2164}, mesh = {CCCTC-Binding Factor/*genetics/metabolism ; Cells, Cultured ; DNA-Binding Proteins/*genetics ; *Gene Expression Regulation ; Gene Ontology ; Humans ; Monocytes/cytology/metabolism ; Regulatory Elements, Transcriptional/*genetics ; T-Lymphocytes/cytology/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {BACKGROUND: Transcriptional target genes show functional enrichment of genes. However, how many and how significantly transcriptional target genes include functional enrichments are still unclear. To address these issues, I predicted human transcriptional target genes using open chromatin regions, ChIP-seq data and DNA binding sequences of transcription factors in databases, and examined functional enrichment and gene expression level of putative transcriptional target genes.

RESULTS: Gene Ontology annotations showed four times larger numbers of functional enrichments in putative transcriptional target genes than gene expression information alone, independent of transcriptional target genes. To compare the number of functional enrichments of putative transcriptional target genes between cells or search conditions, I normalized the number of functional enrichment by calculating its ratios in the total number of transcriptional target genes. With this analysis, native putative transcriptional target genes showed the largest normalized number of functional enrichments, compared with target genes including 5-60% of randomly selected genes. The normalized number of functional enrichments was changed according to the criteria of enhancer-promoter interactions such as distance from transcriptional start sites and orientation of CTCF-binding sites. Forward-reverse orientation of CTCF-binding sites showed significantly higher normalized number of functional enrichments than the other orientations. Journal papers showed that the top five frequent functional enrichments were related to the cellular functions in the three cell types. The median expression level of transcriptional target genes changed according to the criteria of enhancer-promoter assignments (i.e. interactions) and was correlated with the changes of the normalized number of functional enrichments of transcriptional target genes.

CONCLUSIONS: Human putative transcriptional target genes showed significant functional enrichments. Functional enrichments were related to the cellular functions. The normalized number of functional enrichments of human putative transcriptional target genes changed according to the criteria of enhancer-promoter assignments and correlated with the median expression level of the target genes. These analyses and characters of human putative transcriptional target genes would be useful to examine the criteria of enhancer-promoter assignments and to predict the novel mechanisms and factors such as DNA binding proteins and DNA sequences of enhancer-promoter interactions.}, } @article {pmid29363428, year = {2018}, author = {Huang, Y and Cao, Y and Li, J and Liu, Y and Zhong, W and Li, X and Chen, C and Hao, P}, title = {A survey on cellular RNA editing activity in response to Candida albicans infections.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {43}, pmid = {29363428}, issn = {1471-2164}, mesh = {Adenosine/genetics/metabolism ; Alu Elements/genetics ; Animals ; Candida albicans/*genetics ; Candidiasis/*genetics/virology ; Cells, Cultured ; Epithelial Cells/cytology/*metabolism ; *Gene Expression Regulation ; Human Umbilical Vein Endothelial Cells/cytology/*metabolism ; Humans ; Inosine/genetics/metabolism ; Mice ; *RNA Editing ; RNA-Binding Proteins/genetics/*metabolism ; Sequence Analysis, RNA/methods ; Signal Transduction ; }, abstract = {BACKGROUND: Adenosine-to-Inosine (A-to-I) RNA editing is catalyzed by the adenosine deaminase acting on RNA (ADAR) family of enzymes, which induces alterations in mRNA sequence. It has been shown that A-to-I RNA editing events are of significance in the cell's innate immunity and cellular response to viral infections. However, whether RNA editing plays a role in cellular response to microorganism/fungi infection has not been determined. Candida albicans, one of the most prevalent human pathogenic fungi, usually act as a commensal on skin and superficial mucosal, but has been found to cause candidiasis in immunosuppression patients. Previously, we have revealed the up-regulation of A-to-I RNA editing activity in response to different types of influenza virus infections. The current work is designed to study the effect of microorganism/fungi infection on the activity of A-to-I RNA editing in infected hosts.

RESULTS: We first detected and characterized the A-to-I RNA editing events in oral epithelial cells (OKF6) and primary human umbilical vein endothelial cells (HUVEC), under normal growth condition or with C. albicans infection. Eighty nine thousand six hundred forty eight and 60,872 A-to-I editing sites were detected in normal OKF6 and HUVEC cells, respectively. They were validated against the RNA editing databases, DARNED, RADAR, and REDIportal with 50, 80, and 80% success rates, respectively. While over 95% editing sites were detected in Alu regions, among the rest of the editing sites in non repetitive regions, the majority was located in introns and UTRs. The distributions of A-to-I editing activity and editing depth were analyzed during the course of C. albicans infection. While the normalized editing levels of common editing sites exhibited a significant increase, especially in Alu regions, no significant change in the expression of ADAR1 or ADAR2 was observed. Second, we performed further analysis on data from in vivo mouse study with C. albicans infection. One thousand one hundred thirty three and 955 A-to-I editing sites were identified in mouse tongue and kidney tissues, respectively. The number of A-to-I editing events was much smaller than in human epithelial or endothelial cells, due to the lack of Alu elements in mouse genome. Furthermore, during the course of C. albicans infection we observed stable level of A-to-I editing activity in 131 and 190 common editing sites in the mouse tongue and kidney tissues, and found no significant change in ADAR1 or ADAR2 expression (with the exception of ADAR2 displaying a significant increase at 12 h after infection in mouse kidney tissue before returning to normal).

CONCLUSIONS: This work represents the first comprehensive analysis of A-to-I RNA editome in human epithelial and endothelial cells. C. albicans infection of human epithelial and endothelial cells led to the up-regulation of A-to-I editing activities, through a mechanism different from that of viral infections in human hosts. However, the in vivo mouse model with C. albicans infection did not show significant changes in A-to-I editing activities in tongue and kidney tissues. The different results in the mouse model were likely due to the presence of more complex in vivo environments, e.g. circulation and mixed cell types.}, } @article {pmid29363427, year = {2018}, author = {Wang, Y and Li, G and Ma, M and He, F and Song, Z and Zhang, W and Wu, C}, title = {GT-WGS: an efficient and economic tool for large-scale WGS analyses based on the AWS cloud service.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {959}, pmid = {29363427}, issn = {1471-2164}, mesh = {Cloud Computing/*economics ; Cluster Analysis ; *Genome, Human ; Genomics/*methods ; Humans ; Sequence Analysis, DNA/economics/*methods ; *Software ; Whole Genome Sequencing/economics/*methods ; }, abstract = {BACKGROUND: Whole-genome sequencing (WGS) plays an increasingly important role in clinical practice and public health. Due to the big data size, WGS data analysis is usually compute-intensive and IO-intensive. Currently it usually takes 30 to 40 h to finish a 50× WGS analysis task, which is far from the ideal speed required by the industry. Furthermore, the high-end infrastructure required by WGS computing is costly in terms of time and money. In this paper, we aim to improve the time efficiency of WGS analysis and minimize the cost by elastic cloud computing.

RESULTS: We developed a distributed system, GT-WGS, for large-scale WGS analyses utilizing the Amazon Web Services (AWS). Our system won the first prize on the Wind and Cloud challenge held by Genomics and Cloud Technology Alliance conference (GCTA) committee. The system makes full use of the dynamic pricing mechanism of AWS. We evaluate the performance of GT-WGS with a 55× WGS dataset (400GB fastq) provided by the GCTA 2017 competition. In the best case, it only took 18.4 min to finish the analysis and the AWS cost of the whole process is only 16.5 US dollars. The accuracy of GT-WGS is 99.9% consistent with that of the Genome Analysis Toolkit (GATK) best practice. We also evaluated the performance of GT-WGS performance on a real-world dataset provided by the XiangYa hospital, which consists of 5× whole-genome dataset with 500 samples, and on average GT-WGS managed to finish one 5× WGS analysis task in 2.4 min at a cost of $3.6.

CONCLUSIONS: WGS is already playing an important role in guiding therapeutic intervention. However, its application is limited by the time cost and computing cost. GT-WGS excelled as an efficient and affordable WGS analyses tool to address this problem. The demo video and supplementary materials of GT-WGS can be accessed at https://github.com/Genetalks/wgs_analysis_demo .}, } @article {pmid29363426, year = {2018}, author = {Guo, WF and Zhang, SW and Shi, QQ and Zhang, CM and Zeng, T and Chen, L}, title = {A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {924}, pmid = {29363426}, issn = {1471-2164}, mesh = {*Algorithms ; Computational Biology/methods ; Drug Design ; Drug Discovery/*methods ; Humans ; Metabolic Networks and Pathways/*drug effects ; *Models, Biological ; Pharmaceutical Preparations/*analysis ; *Software ; Systems Biology/methods ; }, abstract = {BACKGROUND: The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes).

RESULTS: Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng .

CONCLUSIONS: In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the practical strategic utility of TCOA to incorporate prior drug information into potential drug-target forecasts. Thus applicably, our method paves a novel and efficient way to identify the drug targets for leading the phenotype transitions of underlying biological networks.}, } @article {pmid29363425, year = {2018}, author = {Wu, YW}, title = {ezTree: an automated pipeline for identifying phylogenetic marker genes and inferring evolutionary relationships among uncultivated prokaryotic draft genomes.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {921}, pmid = {29363425}, issn = {1471-2164}, mesh = {Bacteria/*classification/*genetics ; *Biological Evolution ; Biomarkers/*analysis ; Computational Biology/methods ; Genome, Bacterial ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Software ; }, abstract = {BACKGROUND: Inferring phylogenetic trees for newly recovered genomes from metagenomic samples is very useful in determining the identities of uncultivated microorganisms. Even though 16S ribosomal RNA small subunit genes have been established as "gold standard" markers for inferring phylogenetic trees, they usually cannot be assembled very well in metagenomes due to shared regions among 16S genes. Using single-copy marker genes to build genome trees has become increasingly popular for uncultivated species. Predefined marker gene sets were discovered and have been applied in various genomic studies; however these gene sets might not be adequate for novel, uncultivated, draft, or incomplete genomes. The automatic identification of marker gene sets among a set of genomes with different assembly qualities has thus become a very important task for inferring reliable phylogenetic relationships for microbial populations.

RESULTS: A computational pipeline, ezTree, was developed to automatically identify single-copy marker genes for a group of genomes and build phylogenetic trees from the marker genes. Testing ezTree on a group of proteobacteria species revealed that ezTree was highly effective in pinpointing marker genes and constructing reliable trees for different groups of bacterial genomes. Applying ezTree to genomes that were recently recovered from metagenomes also showed that ezTree can help elucidate taxonomic relationships among newly recovered genomes and existing ones.

CONCLUSIONS: The development of ezTree can help scientists build reliable phylogenetic trees for uncultivated species retrieved from environmental samples. The uncovered single-copy marker genes may also provide crucial hints for understanding shared features of a group of microbes. The ezTree pipeline is freely available at https://github.com/yuwwu/ezTree under a GNU GPLv3 license.}, } @article {pmid29363424, year = {2018}, author = {López, Y and Sharma, A and Dehzangi, A and Lal, SP and Taherzadeh, G and Sattar, A and Tsunoda, T}, title = {Success: evolutionary and structural properties of amino acids prove effective for succinylation site prediction.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {923}, pmid = {29363424}, issn = {1471-2164}, mesh = {*Algorithms ; Amino Acid Sequence ; Amino Acids/*chemistry/metabolism ; Computational Biology/methods ; *Evolution, Molecular ; Lysine/*chemistry/metabolism ; *Protein Processing, Post-Translational ; Succinic Acid/*metabolism ; }, abstract = {BACKGROUND: Post-translational modification is considered an important biological mechanism with critical impact on the diversification of the proteome. Although a long list of such modifications has been studied, succinylation of lysine residues has recently attracted the interest of the scientific community. The experimental detection of succinylation sites is an expensive process, which consumes a lot of time and resources. Therefore, computational predictors of this covalent modification have emerged as a last resort to tackling lysine succinylation.

RESULTS: In this paper, we propose a novel computational predictor called 'Success', which efficiently uses the structural and evolutionary information of amino acids for predicting succinylation sites. To do this, each lysine was described as a vector that combined the above information of surrounding amino acids. We then designed a support vector machine with a radial basis function kernel for discriminating between succinylated and non-succinylated residues. We finally compared the Success predictor with three state-of-the-art predictors in the literature. As a result, our proposed predictor showed a significant improvement over the compared predictors in statistical metrics, such as sensitivity (0.866), accuracy (0.838) and Matthews correlation coefficient (0.677) on a benchmark dataset.

CONCLUSIONS: The proposed predictor effectively uses the structural and evolutionary information of the amino acids surrounding a lysine. The bigram feature extraction approach, while retaining the same number of features, facilitates a better description of lysines. A support vector machine with a radial basis function kernel was used to discriminate between modified and unmodified lysines. The aforementioned aspects make the Success predictor outperform three state-of-the-art predictors in succinylation detection.}, } @article {pmid29363423, year = {2018}, author = {Cheng, L and Jiang, Y and Ju, H and Sun, J and Peng, J and Zhou, M and Hu, Y}, title = {InfAcrOnt: calculating cross-ontology term similarities using information flow by a random walk.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {919}, pmid = {29363423}, issn = {1471-2164}, mesh = {Computational Biology/*methods ; Gene Expression Profiling ; *Gene Ontology ; *Gene Regulatory Networks ; Genomics/*methods ; Humans ; *Models, Biological ; Protein Interaction Domains and Motifs ; *Software ; Yeasts/genetics ; }, abstract = {BACKGROUND: Since the establishment of the first biomedical ontology Gene Ontology (GO), the number of biomedical ontology has increased dramatically. Nowadays over 300 ontologies have been built including extensively used Disease Ontology (DO) and Human Phenotype Ontology (HPO). Because of the advantage of identifying novel relationships between terms, calculating similarity between ontology terms is one of the major tasks in this research area. Though similarities between terms within each ontology have been studied with in silico methods, term similarities across different ontologies were not investigated as deeply. The latest method took advantage of gene functional interaction network (GFIN) to explore such inter-ontology similarities of terms. However, it only used gene interactions and failed to make full use of the connectivity among gene nodes of the network. In addition, all existent methods are particularly designed for GO and their performances on the extended ontology community remain unknown.

RESULTS: We proposed a method InfAcrOnt to infer similarities between terms across ontologies utilizing the entire GFIN. InfAcrOnt builds a term-gene-gene network which comprised ontology annotations and GFIN, and acquires similarities between terms across ontologies through modeling the information flow within the network by random walk. In our benchmark experiments on sub-ontologies of GO, InfAcrOnt achieves a high average area under the receiver operating characteristic curve (AUC) (0.9322 and 0.9309) and low standard deviations (1.8746e-6 and 3.0977e-6) in both human and yeast benchmark datasets exhibiting superior performance. Meanwhile, comparisons of InfAcrOnt results and prior knowledge on pair-wise DO-HPO terms and pair-wise DO-GO terms show high correlations.

CONCLUSIONS: The experiment results show that InfAcrOnt significantly improves the performance of inferring similarities between terms across ontologies in benchmark set.}, } @article {pmid29363422, year = {2018}, author = {Makita, Y and Kawashima, M and Lau, NS and Othman, AS and Matsui, M}, title = {Construction of Pará rubber tree genome and multi-transcriptome database accelerates rubber researches.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {922}, pmid = {29363422}, issn = {1471-2164}, mesh = {Biomedical Research ; *Databases, Nucleic Acid ; *Gene Expression Regulation, Plant ; *Genome, Plant ; Hevea/classification/*genetics ; High-Throughput Nucleotide Sequencing/methods ; Molecular Sequence Annotation ; Plant Proteins/*genetics ; RNA, Plant/genetics ; Sequence Analysis, RNA/methods ; *Transcriptome ; }, abstract = {BACKGROUND: Natural rubber is an economically important material. Currently the Pará rubber tree, Hevea brasiliensis is the main commercial source. Little is known about rubber biosynthesis at the molecular level. Next-generation sequencing (NGS) technologies brought draft genomes of three rubber cultivars and a variety of RNA sequencing (RNA-seq) data. However, no current genome or transcriptome databases (DB) are organized by gene.

RESULTS: A gene-oriented database is a valuable support for rubber research. Based on our original draft genome sequence of H. brasiliensis RRIM600, we constructed a rubber tree genome and transcriptome DB. Our DB provides genome information including gene functional annotations and multi-transcriptome data of RNA-seq, full-length cDNAs including PacBio Isoform sequencing (Iso-Seq), ESTs and genome wide transcription start sites (TSSs) derived from CAGE technology. Using our original and publically available RNA-seq data, we calculated co-expressed genes for identifying functionally related gene sets and/or genes regulated by the same transcription factor (TF). Users can access multi-transcriptome data through both a gene-oriented web page and a genome browser. For the gene searching system, we provide keyword search, sequence homology search and gene expression search; users can also select their expression threshold easily.

CONCLUSION: The rubber genome and transcriptome DB provides rubber tree genome sequence and multi-transcriptomics data. This DB is useful for comprehensive understanding of the rubber transcriptome. This will assist both industrial and academic researchers for rubber and economically important close relatives such as R. communis, M. esculenta and J. curcas. The Rubber Transcriptome DB release 2017.03 is accessible at http://matsui-lab.riken.jp/rubber/ .}, } @article {pmid29363421, year = {2018}, author = {Lim, WC and Khan, AM}, title = {Mapping HLA-A2, -A3 and -B7 supertype-restricted T-cell epitopes in the ebolavirus proteome.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {42}, pmid = {29363421}, issn = {1471-2164}, mesh = {Ebolavirus/*immunology/isolation & purification ; Epitope Mapping/*methods ; Epitopes, T-Lymphocyte/*immunology ; Genetic Variation ; HLA-A2 Antigen/genetics/immunology/metabolism ; HLA-A3 Antigen/genetics/immunology/metabolism ; HLA-B7 Antigen/genetics/immunology/metabolism ; Hemorrhagic Fever, Ebola/*immunology/metabolism/virology ; Humans ; Proteome/*immunology/metabolism ; T-Lymphocytes, Cytotoxic/immunology ; Viral Proteins/*immunology ; }, abstract = {BACKGROUND: Ebolavirus (EBOV) is responsible for one of the most fatal diseases encountered by mankind. Cellular T-cell responses have been implicated to be important in providing protection against the virus. Antigenic variation can result in viral escape from immune recognition. Mapping targets of immune responses among the sequence of viral proteins is, thus, an important first step towards understanding the immune responses to viral variants and can aid in the identification of vaccine targets. Herein, we performed a large-scale, proteome-wide mapping and diversity analyses of putative HLA supertype-restricted T-cell epitopes of Zaire ebolavirus (ZEBOV), the most pathogenic species among the EBOV family.

METHODS: All publicly available ZEBOV sequences (14,098) for each of the nine viral proteins were retrieved, removed of irrelevant and duplicate sequences, and aligned. The overall proteome diversity of the non-redundant sequences was studied by use of Shannon's entropy. The sequences were predicted, by use of the NetCTLpan server, for HLA-A2, -A3, and -B7 supertype-restricted epitopes, which are relevant to African and other ethnicities and provide for large (~86%) population coverage. The predicted epitopes were mapped to the alignment of each protein for analyses of antigenic sequence diversity and relevance to structure and function. The putative epitopes were validated by comparison with experimentally confirmed epitopes.

RESULTS & DISCUSSION: ZEBOV proteome was generally conserved, with an average entropy of 0.16. The 185 HLA supertype-restricted T-cell epitopes predicted (82 (A2), 37 (A3) and 66 (B7)) mapped to 125 alignment positions and covered ~24% of the proteome length. Many of the epitopes showed a propensity to co-localize at select positions of the alignment. Thirty (30) of the mapped positions were completely conserved and may be attractive for vaccine design. The remaining (95) positions had one or more epitopes, with or without non-epitope variants. A significant number (24) of the putative epitopes matched reported experimentally validated HLA ligands/T-cell epitopes of A2, A3 and/or B7 supertype representative allele restrictions. The epitopes generally corresponded to functional motifs/domains and there was no correlation to localization on the protein 3D structure. These data and the epitope map provide important insights into the interaction between EBOV and the host immune system.}, } @article {pmid29363420, year = {2018}, author = {Liu, YC and Chiu, YJ and Li, JR and Sun, CH and Liu, CC and Huang, HD}, title = {Biclustering of transcriptome sequencing data reveals human tissue-specific circular RNAs.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {958}, pmid = {29363420}, issn = {1471-2164}, mesh = {*Algorithms ; Biomarkers/*metabolism ; Brain/metabolism ; Cluster Analysis ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Organ Specificity ; RNA/*genetics ; *Transcriptome ; }, abstract = {BACKGROUND: Emerging evidence has been experimentally confirmed the tissue-specific expression of circRNAs (circRNAs). Global identification of human tissue-specific circRNAs is crucial for the functionality study, which facilitates the discovery of circRNAs for potential diagnostic biomarkers.

RESULTS: In this study, circRNA back-splicing junctions were identified from 465 publicly available transcriptome sequencing samples. The number of reads aligned to these identified junctions was normalized with the read length and sequence depth for each sample. We generated 66 models representing enriched circRNAs among human tissue transcriptome through biclustering algorithm. The result provides thousands of newly identified human tissue-specific circRNAs.

CONCLUSIONS: This result suggests that expression of circRNAs is not prompted by random splicing error but serving molecular functional roles. We also identified circRNAs enriched within circulating system, which, along with identified tissue-specific circRNAs, can serve as potential diagnostic biomarkers.}, } @article {pmid29363419, year = {2018}, author = {Chen, K and Liu, L and Zhang, X and Yuan, Y and Ren, S and Guo, J and Wang, Q and Liao, P and Li, S and Cui, X and Li, YF and Zheng, Y}, title = {Phased secondary small interfering RNAs in Panaxnotoginseng.}, journal = {BMC genomics}, volume = {19}, number = {Suppl 1}, pages = {41}, pmid = {29363419}, issn = {1471-2164}, mesh = {Gene Expression Regulation, Plant ; *Genome, Plant ; High-Throughput Nucleotide Sequencing/*methods ; Panax notoginseng/*genetics ; Plant Proteins/*genetics ; RNA, Small Interfering/classification/*genetics ; Sequence Analysis, RNA/*methods ; }, abstract = {BACKGROUND: Recent results demonstrated that either non-coding or coding genes generate phased secondary small interfering RNAs (phasiRNAs) guided by specific miRNAs. Till now, there is no studies for phasiRNAs in Panax notoginseng (Burk.) F.H. Chen (P. notoginseng), an important traditional Chinese herbal medicinal plant species.

METHODS: Here we performed a genome-wide discovery of phasiRNAs and its host PHAS loci in P. notoginseng by analyzing small RNA sequencing profiles. Degradome sequencing profile was used to identify the trigger miRNAs of these phasiRNAs and potential targets of phasiRNAs. We also used RLM 5'-RACE to validate some of the identified phasiRNA targets.

RESULTS: After analyzing 24 small RNA sequencing profiles of P. notoginseng, 204 and 90 PHAS loci that encoded 21 and 24 nucleotide (nt) phasiRNAs, respectively, were identified. Furthermore, we found that phasiRNAs produced from some pentatricopeptide repeat-contain (PPR) genes target another layer of PPR genes as validated by both the degradome sequencing profile and RLM 5'-RACE analysis. We also found that miR171 with 21 nt triggers the generations of 21 nt phasiRNAs from its conserved targets.

CONCLUSIONS: We validated that some phasiRNAs generated from PPRs and TASL genes are functional by targeting other PPRs in trans. These results provide the first set of PHAS loci and phasiRNAs in P. notoginseng, and enhance our understanding of PHAS in plants.}, } @article {pmid29363112, year = {2018}, author = {Esteve-Altava, B and Molnar, JL and Johnston, P and Hutchinson, JR and Diogo, R}, title = {Anatomical network analysis of the musculoskeletal system reveals integration loss and parcellation boost during the fins-to-limbs transition.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {601-618}, doi = {10.1111/evo.13430}, pmid = {29363112}, issn = {1558-5646}, abstract = {Tetrapods evolved from within the lobe-finned fishes around 370 Ma. The evolution of limbs from lobe-fins entailed a major reorganization of the skeletal and muscular anatomy of appendages in early tetrapods. Concurrently, a degree of similarity between pectoral and pelvic appendages also evolved. Here, we compared the anatomy of appendages in extant lobe-finned fishes (Latimeria and Neoceratodus) and anatomically plesiomorphic amphibians (Ambystoma, Salamandra) and amniotes (Sphenodon) to trace and reconstruct the musculoskeletal changes that took place during the fins-to-limbs transition. We quantified the anatomy of appendages using network analysis. First, we built network models-in which nodes represent bones and muscles, and links represent their anatomical connections-and then we measured network parameters related to their anatomical integration, heterogeneity, and modularity. Our results reveal an evolutionary transition toward less integrated, more modular appendages. We interpret this transition as a diversification of muscle functions in tetrapods compared to lobe-finned fishes. Limbs and lobe-fins show also a greater similarity between their pectoral and pelvic appendages than ray-fins do. These findings on extant species provide a basis for future quantitative and comprehensive reconstructions of the anatomy of limbs in early tetrapod fossils, and a way to better understand the fins-to-limbs transition.}, } @article {pmid29363111, year = {2018}, author = {Blankers, T and Vilaça, ST and Waurick, I and Gray, DA and Hennig, RM and Mazzoni, CJ and Mayer, F and Berdan, EL}, title = {Demography and selection shape transcriptomic divergence in field crickets.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {553-567}, doi = {10.1111/evo.13435}, pmid = {29363111}, issn = {1558-5646}, abstract = {Gene flow, demography, and selection can result in similar patterns of genomic variation and disentangling their effects is key to understanding speciation. Here, we assess transcriptomic variation to unravel the evolutionary history of Gryllus rubens and Gryllus texensis, cryptic field cricket species with highly divergent mating behavior. We infer their demographic history and screen their transcriptomes for footprints of selection in the context of the inferred demography. We find strong support for a long history of bidirectional gene flow, which ceased during the late Pleistocene, and a bottleneck in G. rubens consistent with a peripatric origin of this species. Importantly, the demographic history has likely strongly shaped patterns of genetic differentiation (empirical FST distribution). Concordantly, FST -based selection detection uncovers a large number of outliers, likely comprising many false positives, echoing recent theoretical insights. Alternative genetic signatures of positive selection, informed by the demographic history of the sibling species, highlighted a smaller set of loci; many of these are candidates for controlling variation in mating behavior. Our results underscore the importance of demography in shaping overall patterns of genetic divergence and highlight that examining both demography and selection facilitates a more complete understanding of genetic divergence during speciation.}, } @article {pmid29362894, year = {2018}, author = {Haug, C and Rötzer, MAIN}, title = {The ontogeny of the 300 million year old xiphosuran Euproops danae (Euchelicerata) and implications for resolving the Euproops species complex.}, journal = {Development genes and evolution}, volume = {228}, number = {1}, pages = {63-74}, pmid = {29362894}, issn = {1432-041X}, support = {DFG HA 7066/3-1//Deutsche Forschungsgemeinschaft/International ; none//Bayerische Gleichstellungsförderung LMU/International ; }, mesh = {Animals ; Arthropods/*anatomy & histology/*genetics/growth & development ; *Fossils ; Morphogenesis ; }, abstract = {Xiphosurans have often been considered as archaic appearing cheliceratan arthropods, with a rich fossil record. We describe here parts of the post-embryonic ontogeny of the 300 million year old xiphosuran Euproops danae (Xiphosura sensu stricto, Euchelicerata), from the Mazon Creek Lagerstätte (Upper Carboniferous), USA. Recently, the ontogeny of a closely related species, Euproops sp. from the Upper Carboniferous Piesberg quarry, Osnabrück, Germany (informally called 'Piesproops'), has been reconstructed. This analysis has drawn characters into question that were used to differentiate E. danae from another species occurring at the same time, Euproops rotundatus from the British Middle Coal Measures. More precisely, early post-embryonic stages of Piesproops resemble E. danae; later stages resemble E. rotundatus. Based on this earlier study, the here-described reinvestigation of E. danae has been performed as the ontogenetic sequence itself may yield more reliable characters for differentiating species of Euproops. We could identify eight different growth stages for E. danae. This ontogenetic sequence shows a comparable growth to that of Piesproops, but differs markedly in the development of the opisthosomal flange. This character may serve as a basis for reliably differentiating these species. Additionally, analysing the ontogeny of further species may offer the basis for identifying heterochronic shifts in the evolution of xiphosurans.}, } @article {pmid29362880, year = {2018}, author = {Li, W and Lee, SY and Kang, IK and Ten, LN and Jung, HY}, title = {Spirosoma agri sp. nov., Isolated from Apple Orchard Soil.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {694-700}, pmid = {29362880}, issn = {1432-0991}, support = {162S-4-3-1727//The Brain Pool Program of 2016 through the Korean Federation of Science and Technology Societies (KOFST) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea/ ; }, mesh = {Base Composition/genetics ; Cytophagaceae/classification/*genetics/*isolation & purification/metabolism ; DNA, Bacterial/genetics ; *Malus ; Phenotype ; Phospholipids/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Soil Microbiology ; }, abstract = {A Gram-negative, non-motile, rod-shaped, aerobic bacterial strain, designated S7-3-3T, was isolated from apple orchard soil in Gyeongsangnam-do province, South Korea, and was characterized taxonomically using a polyphasic approach. Phylogenetic analysis based on 16S rRNA gene sequence showed that strain S7-3-3T belonged to the family Cytophagaceae in the phylum Bacteroidetes was most closely related to Spirosoma rigui WPCB118T (94.3%), Spirosoma pulveris JSH5-14T (93.9%), and Spirosoma linguale DSM 74T (93.7%). The strain showed typical chemotaxonomic characteristics of the genus Spirosoma with a predominant respiratory quinone of menaquinone MK-7 and the major fatty acids of summed feature 3 (C16:1 ω7c/C16:1 ω6c; 43.9%) and C16:1 ω5c (25.6%). The G+C content of genomic DNA was 49.6 mol%. The polar lipid profile contained major amounts of phosphatidylethanolamine, an unidentified aminophospholipid, and an unidentified polar lipid. Phenotypic and chemotaxonomic data supported the affiliation of strain S7-3-3T with the genus Spirosoma. The results of physiological and biochemical tests showed the genotypic and phenotypic differentiation of the isolate from recognized Spirosoma species. On the basis of its phenotypic properties, genotypic distinctiveness, and chemotaxonomic features, strain S7-3-3T represents a novel species of the genus Spirosoma, for which the name Spirosoma agri sp. nov. is proposed. The type strain is S7-3-3T (= KCTC 52727T = JCM 32199T).}, } @article {pmid29362879, year = {2018}, author = {Zha, GD and Yang, DH and Wang, JJ and Yang, B and Yu, HS}, title = {Infection Function of Adhesin-Like Protein ALP609 from Spiroplasma melliferum CH-1.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {701-708}, pmid = {29362879}, issn = {1432-0991}, support = {30870002//National Natural Science Foundation of China/ ; }, mesh = {Adhesins, Bacterial/*chemistry ; Animals ; Bees ; DNA, Bacterial/genetics ; Microscopy, Fluorescence ; Spiroplasma/*chemistry/pathogenicity ; }, abstract = {Spiroplasma melliferum is the causative agent of spiroplasmosis in honeybees. During infection, adhesion of spiroplasmas to the host cells through adhesion factors is a crucial step. In this study, we identified an adhesin-like protein (ALP609) in S. melliferum CH-1 and investigated its role in the infection. To determine whether ALP609 is an adhesion factor, we performed indirect immunofluorescence microscopy to visualize its adhesion properties. Subsequently, an infection model of S. melliferum CH-1 was established using primary midgut cells of Apis mellifera to examine the adhesion and invasion of spiroplasma using anti-ALP609 antibodies inhibition assays and competition assays with recombinant ALP609 in vitro. We found that anti-ALP609 antibodies could inhibit the adhesion and invasion of spiroplasma to the midgut cells of A. mellifera and reduce midgut cell invasion on increased exposure to recombinant ALP609. To the best of our knowledge, this is the first report identifying adhesion-related factors in S. melliferum. Our results suggested that ALP609 is an adhesin-like protein critical for invasion of S. melliferum CH-1 into midgut cells of A. mellifera.}, } @article {pmid29361986, year = {2018}, author = {Anokye, R and Acheampong, E and Mprah, WK and Sarpong, E}, title = {Perceived causes and risk factors of Buruli ulcer among patients at Agogo Presbyterian hospital in Ashanti Region of Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {64}, pmid = {29361986}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Buruli Ulcer/*diagnosis/*epidemiology ; Female ; Ghana/epidemiology ; *Hospitals ; Humans ; Incidence ; Male ; Patients/*statistics & numerical data ; Protestantism ; Risk Factors ; Surveys and Questionnaires ; Young Adult ; }, abstract = {OBJECTIVE: The incidence of Buruli ulcer has been recorded in about 30 countries globally and Africa seems to be the most affected area. The study sought to determine perceived causes and risk factors of Buruli ulcer among patients who visit the Agogo hospital in Asante-Akim North District in the Ashanti region of Ghana. A descriptive study design was adopted using a simple random sampling technique to select 400 patients attending The Presbyterian Hospital at Agogo. Data was collected using a structured questionnaire and analysed using SPSS version 16.0.

RESULTS: Buruli ulcer was perceived as a disease caused by witchcraft (38%), enemies (15%), as well as not pouring libation or praying (16%). Also, increased appetite (30%), oedema or swelling on the skin (29%) and over weight (23%) was perceived as signs and symptoms of Buruli ulcer and a section of the respondents (53%) did not know any risk factor. The age of respondents, gender and level of education were found to determine knowledge of Buruli ulcer (P ≤ .05). Public Educations and campaigns should focus on causes and risk factors to ensure that there is adequate knowledge among the general public on Buruli ulcer.}, } @article {pmid29361980, year = {2018}, author = {Ndzo, JA and Jackson, A}, title = {Outcomes of children aged 6-59 months with severe acute malnutrition at the GADO Outpatient Therapeutic Center in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {68}, pmid = {29361980}, issn = {1756-0500}, mesh = {Cameroon ; Child, Preschool ; Female ; Hospitalization/statistics & numerical data ; Humans ; Infant ; Length of Stay/statistics & numerical data ; Male ; Outcome Assessment (Health Care)/methods/*statistics & numerical data ; Outpatients/*statistics & numerical data ; Patient Discharge/statistics & numerical data ; Protein-Energy Malnutrition/physiopathology/therapy ; Retrospective Studies ; Severe Acute Malnutrition/physiopathology/*therapy ; *Weight Gain ; }, abstract = {OBJECTIVE: We aimed to assess outcomes [rates of recovery, default, case fatality; rate of weight gain and rate of Mean Upper Arm Circumference (MUAC) gain] of children aged 6-59 months with severe acute malnutrition (SAM) at the Outpatient Therapeutic Center at Gado Refugee Camp, Cameroon, in relation to international standards. We retrospectively analysed files of 254 children with SAM aged 6-59 months admitted from April 2015 to August 2016.

RESULTS: 72.8% got discharged as recovered, 0.8% died and none defaulted. 26.8% got referred to stabilization center, mostly for poor weight gain (44.1%). Mean rate of weight gain was 4.4 g/kg/day and MUAC gain 0.3 mm/cm/day; median duration of treatment 44.5 days. Amongst those with marasmus, kwashiorkor and marasmic kwashiorkor, median duration of stay was 48, 24.5 and 36.3 days (p = 0.002); recovery rates were similar 73, 71.4, 71.4% respectively (p = 0.7); Median rates of weight gain, 4.4, 6.7 and 8.1 g/kg/day (p = 0.05). 49 children had been incorrectly diagnosed and treated as SAM. International Standards were met in terms of case fatality rate and default rate but not rates of recovery and weight gain. Separate gender charts must be used to calculate weight for height z scores as combined charts cause significant errors.}, } @article {pmid29361978, year = {2018}, author = {Ma, H and Gao, G and Weber, GM}, title = {Use of DAVID algorithms for clustering custom annotated gene lists in a non-model organism, rainbow trout.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {63}, pmid = {29361978}, issn = {1756-0500}, support = {8082-31000-012//USDA-ARS CRIS/ ; }, mesh = {*Algorithms ; Animals ; Cluster Analysis ; Computational Biology/methods ; Fish Proteins/classification/*genetics ; Gene Expression Profiling/*methods ; Gene Ontology ; Molecular Sequence Annotation/*methods ; Oncorhynchus mykiss/*genetics ; Reproducibility of Results ; }, abstract = {OBJECTIVE: The DAVID gene functional classification tool requires adaptations for use in non-model species and there is little available information to guide selection of a kappa score. Our objective was to develop an R-script that allows custom gene identifiers and novel annotation information to be incorporated into analyses, then use such data to evaluate the number of differentially expressed genes (DEGs) in a comparison based on kappa score selection.

RESULTS: Using an R-script we developed and multiple data sets ranging from 555 to 3340 annotated DEGs from a study in rainbow trout, we found the percentage of DEGs harbored within a module and the number of genes shared among multiple modules decreased with increasing kappa score regardless of the number of DEGs in the comparison. The number of genes in enriched modules peaked at a kappa score of 0.5 for the comparisons with 3340 and 1313 DEGs and 0.3 for 555 DEGs. The number of genes harbored within enriched modules generally decreased with increasing kappa score; however, this was affected by whether the largest modules were significantly enriched. Large non-enriched modules can be reanalyzed using a higher kappa score resulting in some of the genes clustering in smaller enriched modules.}, } @article {pmid29361977, year = {2018}, author = {Pinceel, T and Buschke, F and Weckx, M and Brendonck, L and Vanschoenwinkel, B}, title = {Climate change jeopardizes the persistence of freshwater zooplankton by reducing both habitat suitability and demographic resilience.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {2}, pmid = {29361977}, issn = {1472-6785}, support = {12F0716N//FWO/International ; }, abstract = {BACKGROUND: Higher temperatures and increased environmental variability under climate change could jeopardize the persistence of species. Organisms that rely on short windows of rainfall to complete their life-cycles, like desert annual plants or temporary pool animals, may be particularly at risk. Although some could tolerate environmental changes by building-up banks of propagules (seeds or eggs) that buffer against catastrophes, climate change will threaten this resilience mechanism if higher temperatures reduce propagule survival. Using a crustacean model species from temporary waters, we quantified experimentally the survival and dormancy of propagules under anticipated climate change and used these demographic parameters to simulate long term population dynamics.

RESULTS: By exposing propagules to present-day and projected daily temperature cycles in an 8 month laboratory experiment, we showed how increased temperatures reduce survival rates in the propagule bank. Integrating these reduced survival rates into population models demonstrated the inability of the bank to maintain populations; thereby exacerbating extinction risk caused by shortened growing seasons.

CONCLUSIONS: Overall, our study demonstrates that climate change could threaten the persistence of populations by both reducing habitat suitability and eroding life-history strategies that support demographic resilience.}, } @article {pmid29361976, year = {2018}, author = {Morgan, MJ and Lurie, DM and Villamil, AJ}, title = {Evaluation of tumor volume reduction of nasal carcinomas versus sarcomas in dogs treated with definitive fractionated megavoltage radiation: 15 cases (2010-2016).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {70}, pmid = {29361976}, issn = {1756-0500}, mesh = {Animals ; Carcinoma/diagnostic imaging/radiotherapy/*veterinary ; Dog Diseases/diagnostic imaging/*radiotherapy ; Dogs ; Dose Fractionation, Radiation ; Female ; Male ; Nose Neoplasms/diagnostic imaging/radiotherapy/*veterinary ; Outcome Assessment (Health Care)/methods/statistics & numerical data ; Sarcoma/diagnostic imaging/radiotherapy/*veterinary ; Tomography, X-Ray Computed/methods ; Tumor Burden/radiation effects ; }, abstract = {OBJECTIVE: Local control is a major challenge in treating canine nasal tumors, and cytoreduction following radiation therapy has been recommended to extend survival and to delay local recurrence. Our objective was to compare the effect of definitive radiotherapy on the tumor volume of intranasal carcinomas compared to sarcomas. We evaluated 15 dogs that received radiotherapy within 1 month of initial CT scan, and post radiation CT scans performed within 3 months of completing full course definitive megavoltage radiation. Tumor reduction volume based on CT scans were obtained and compared between carcinoma and sarcoma groups.

RESULTS: The following tumor types were treated; carcinoma (8/15), sarcoma (7/15). The mean nasal tumor size before radiation therapy was 24.5 cm3 and tumor size after radiation therapy was 13.5 cm3 resulting in a mean reduction of 55.1% reduction in tumor size for both carcinomas and sarcomas. The carcinoma group displayed a volume reduction of 67.1% (SD ± 16.9) and the sarcoma group displayed a volume reduction of 21.3% (SD ± 39.7). Within the study period carcinomas were more responsive in the reduction of volume than sarcomas with fractionated megavoltage radiation.}, } @article {pmid29361974, year = {2018}, author = {Ranjan, P and Kateriya, S}, title = {Localization and dimer stability of a newly identified microbial rhodopsin from a polar, non-motile green algae.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {65}, pmid = {29361974}, issn = {1756-0500}, support = {JRF//University Grants Commission/ ; }, mesh = {Algal Proteins/chemistry/genetics/*metabolism ; Amino Acid Sequence ; Antarctic Regions ; Cell Membrane/*metabolism/radiation effects ; Chlorophyta/genetics/*metabolism ; Immunoblotting ; Light ; Protein Multimerization ; Protein Stability ; Proton Pumps/genetics/metabolism ; Rhodopsin/chemistry/genetics/*metabolism ; Sequence Homology, Amino Acid ; }, abstract = {OBJECTIVE: The eukaryotic plasma membrane localized light-gated proton-pumping rhodopsins possesses great optogenetic applications for repolarization (silencing) of the neuronal activity simply by light illumination. Very few plasma membrane localized proton-pumping rhodopsins of a eukaryotic origin are known that have optogenetic potential. Our objective was to identify and characterize microbial rhodopsin of an eukaryotic origin that expresses on plasma membrane. The plasma membrane localized light-gated proton pump of an eukaryotic origin hold great promise to be used as an optogenetic tools for the neurobiology.

RESULTS: Here, we had characterized the cellular expression and membrane localization of a new rhodopsin in Antarctican algae Coccomyxa subellipsoidea. It is the first algal ion pumping rhodopsin that localizes to the plasma membrane of the eukaryotic cells. Coccomyxa subellipsoidea rhodopsin exists in the monomeric and dimeric state both the in vivo and in vitro. The dimeric form of the Coccomyxa subellipsoidea rhodopsin is resistant to heat and detergent denaturants.}, } @article {pmid29361972, year = {2018}, author = {Popis, MC and Wagner, RE and Constantino-Casas, F and Blanco, S and Frye, M}, title = {Considerations for skin carcinogenesis experiments using inducible transgenic mouse models.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {67}, pmid = {29361972}, issn = {1756-0500}, support = {C10701/A15181//Cancer Research UK/United Kingdom ; MR/M01939X/1//Medical Research Council/United Kingdom ; G0801904//Medical Research Council/United Kingdom ; 15-0168//Worldwide Cancer Research/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Carcinoma, Squamous Cell/genetics/*pathology ; Cell Transformation, Neoplastic/genetics/pathology ; Disease Progression ; Gene Expression Regulation, Neoplastic/drug effects ; Genes, ras/genetics ; Mice, Transgenic ; Papilloma/genetics/*pathology ; Skin/drug effects/metabolism/*pathology ; Skin Neoplasms/genetics/*pathology ; Tamoxifen/administration & dosage ; Tumor Suppressor Protein p53/genetics ; }, abstract = {OBJECTIVE: This study was designed to estimate the percentage of non-malignant skin tumours (papillomas) progressing to malignant squamous cell carcinomas (SCCs) in a carcinogenesis study using established transgenic mouse models. In our skin cancer model, we conditionally induced oncogenic point mutant alleles of p53 and k-ras in undifferentiated, basal cells of the epidermis.

RESULTS: Upon activation of the transgenes through administration of tamoxifen, the vast majority of mice (> 80%) developed skin papillomas, yet primarily around the mouth. Since these tumours hindered the mice eating, they rapidly lost weight and needed to be culled before the papillomas progressed to SCCs. The mouth papillomas formed regardless of the route of application, including intraperitoneal injections, local application to the back skin, or subcutaneous insertion of a tamoxifen pellet. Implantation of a slow releasing tamoxifen pellet into 18 mice consistently led to papilloma formation, of which only one progressed to a malignant SCC. Thus, the challenges for skin carcinogenesis studies using this particular cancer mouse model are low conversion rates of papillomas to SCCs and high frequencies of mouth papilloma formation.}, } @article {pmid29361970, year = {2018}, author = {Neelapaijit, A and Pinyopornpanish, M and Simcharoen, S and Kuntawong, P and Wongpakaran, N and Wongpakaran, T}, title = {Psychometric properties of a Thai version internet addiction test.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {69}, pmid = {29361970}, issn = {1756-0500}, mesh = {Behavior, Addictive/*diagnosis ; Female ; Humans ; Internet ; Male ; Psychometrics/*methods ; Reproducibility of Results ; *Surveys and Questionnaires ; Thailand ; *Translations ; Young Adult ; }, abstract = {OBJECTIVE: The aim was to assess the reliability and validity of a Thai version internet addiction test.

RESULTS: Cronbach's alpha for the Thai version of the internet addiction test was 0.89. A three-factor model showed the best fit with the data for the whole sample, whereas the hypothesized six-factor model, as well as a unidimensional model of the internet addiction test, failed to demonstrate acceptable fit with the data. Three factors, namely functional impairment, withdrawal symptoms and loss of control, exhibited Cronbach's alphas of 0.81, 0.81, and 0.70, respectively. Item 4, 'to form new relationships with online users', yielded the lowest loading coefficient of all items. Positive correlations between the internet addiction test and UCLA loneliness scores were found. The Thai version of the internet addiction test was considered reliable and valid, and has sufficient unidimensionality to calculate for total score in screening for excessive internet use.}, } @article {pmid29361969, year = {2018}, author = {Wilson, MAG and Kurrle, S and Wilson, I}, title = {Medical student attitudes towards older people: a critical review of quantitative measures.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {71}, pmid = {29361969}, issn = {1756-0500}, mesh = {Aged ; *Attitude of Health Personnel ; Female ; Geriatrics/education ; Health Knowledge, Attitudes, Practice ; *Health Services for the Aged ; Humans ; Male ; Students, Medical/*psychology ; *Surveys and Questionnaires ; }, abstract = {OBJECTIVES: Further research into medical student attitudes towards older people is important, and requires accurate and detailed evaluative methodology. The two objectives for this paper are: (1) From the literature, to critically review instruments of measure for medical student attitudes towards older people, and (2) To recommend the most appropriate quantitative instrument for future research into medical student attitudes towards older people.

RESULTS: A SCOPUS and Ovid cross search was performed using the keywords Attitude and medical student and aged or older or elderly. This search was supplemented by manual searching, guided by citations in articles identified by the initial literature search, using the SCOPUS and PubMed databases. International studies quantifying medical student attitudes have demonstrated neutral to positive attitudes towards older people, using various instruments. The most commonly used instruments are the Ageing Semantic Differential (ASD) and the University of California Los Angeles Geriatric Attitudes Scale, with several other measures occasionally used. All instruments used to date have inherent weaknesses. A reliable and valid instrument with which to quantify modern medical student attitudes towards older people has not yet been developed. Adaptation of the ASD for contemporary usage is recommended.}, } @article {pmid29361966, year = {2018}, author = {Amoah, VMK and Anokye, R and Acheampong, E and Dadson, HR and Osei, M and Nadutey, A}, title = {The experiences of people with diabetes-related lower limb amputation at the Komfo Anokye Teaching Hospital (KATH) in Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {66}, pmid = {29361966}, issn = {1756-0500}, mesh = {Adult ; *Amputation ; Amputees/*psychology/rehabilitation ; Diabetes Complications/*surgery ; Female ; Ghana ; *Hospitals, Teaching ; Humans ; Interviews as Topic ; Lower Extremity/*surgery ; Male ; Middle Aged ; Qualitative Research ; Quality of Life ; }, abstract = {OBJECTIVE: Lower limb amputation not only causes major disfigurement, but renders people less mobile and at risk of loss of independence. Yet with appropriate rehabilitation, many people can learn to walk or function again and live high quality lives. This study sought to explore the experiences of patients with diabetes-related lower limb amputation at the Komfo Anokye Teaching Hospital. An exploratory study design was adopted using a qualitative approach and a purposive sampling to select 10 participants for the study. A semi-structured interview guide was used with an in-depth face-to-face interview. The interview was tape-recorded with an audio recorder while notes were taken in addition to the audio recording.

RESULTS: There were varying degrees of experiences ranging from physical as well as psychological and economic challenges. Amputees had to cope with playing entirely new roles after the amputation. They also experienced some economic challenges which were as a result of their inability to work. Some of the amputees consoled themselves with the fact that, despite their condition, they were better than other people. Others believed that whatever happened was Gods doing and nothing could be done about it. This self-consolation and the belief in God helped them to cope.}, } @article {pmid29361957, year = {2018}, author = {Mchedlishvili, N and Matthews, HK and Corrigan, A and Baum, B}, title = {Two-step interphase microtubule disassembly aids spindle morphogenesis.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {14}, pmid = {29361957}, issn = {1741-7007}, support = {9786//Cancer Research UK/United Kingdom ; C1529/A17343//Cancer Research UK/United Kingdom ; MC_U12266B//Medical Research Council/United Kingdom ; }, abstract = {BACKGROUND: Entry into mitosis triggers profound changes in cell shape and cytoskeletal organisation. Here, by studying microtubule remodelling in human flat mitotic cells, we identify a two-step process of interphase microtubule disassembly.

RESULTS: First, a microtubule-stabilising protein, Ensconsin/MAP7, is inactivated in prophase as a consequence of its phosphorylation downstream of Cdk1/cyclin B. This leads to a reduction in interphase microtubule stability that may help to fuel the growth of centrosomally nucleated microtubules. The peripheral interphase microtubules that remain are then rapidly lost as the concentration of tubulin heterodimers falls following dissolution of the nuclear compartment boundary. Finally, we show that a failure to destabilise microtubules in prophase leads to the formation of microtubule clumps, which interfere with spindle assembly.

CONCLUSIONS: This analysis highlights the importance of the step-wise remodelling of the microtubule cytoskeleton and the significance of permeabilisation of the nuclear envelope in coordinating the changes in cellular organisation and biochemistry that accompany mitotic entry.}, } @article {pmid29361930, year = {2018}, author = {Piao, DR and Liu, X and Di, DD and Xiao, P and Zhao, ZZ and Xu, LQ and Tian, GZ and Zhao, HY and Fan, WX and Cui, BY and Jiang, H}, title = {Genetic polymorphisms identify in species/biovars of Brucella isolated in China between 1953 and 2013 by MLST.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {7}, pmid = {29361930}, issn = {1471-2180}, support = {2013ZX10004805-005//National Key Program for Infectious Diseases of China/International ; 81271900//The National Nature Science Foundation/International ; }, mesh = {Animals ; Brucella/*classification/*genetics/*isolation & purification/pathogenicity ; Brucellosis/diagnosis/*epidemiology/*microbiology/veterinary ; China/epidemiology ; Cluster Analysis ; DNA, Bacterial/genetics ; Endemic Diseases ; Genes, Bacterial/*genetics ; Genetic Variation ; Genotype ; Humans ; Molecular Epidemiology ; Multilocus Sequence Typing/*methods ; Phylogeny ; *Polymorphism, Genetic ; }, abstract = {BACKGROUND: Brucellosis incidence in China is divided into three stages: high incidence (1950s-1960s), decline (1970s-1980s), and re-emergence (1990s-2010s). At the re-emergence stage, Brucellosis incidence grew exponentially and spread to all 32 provinces. We describe the magnitude and the etiological distribution changes in mainland China by genotyping data and emphasize its recent reemergence. We also provide the genetic diversity and molecular epidemiological characteristics of Brucella.

RESULTS: From a total of 206 Brucella isolates, 19 MLST genotypes (STs) were identified and 13 new STs(ST71-83)were found. MLST grouped the population into three clusters. B. melitensis, B. abortus and B. suis were grouped into cluster 1, 2 and 3 respectively. The predominant genotype in the first cluster by MLST, remained unchanged during the three stages. However, the proportion of genotypes in the three stages had changed. More isolates were clustered in ST8 at the re-emergence stage. STs71-74, which were not found in the two former stages, appeared at the re-emergence stage.

CONCLUSIONS: The changing molecular epidemiology of brucellosis improve our understanding of apparent geographic expansion from the historically affected north of China to southern provinces in recent reemergence.}, } @article {pmid29361928, year = {2018}, author = {Hu, CW and Li, H and Qutub, AA}, title = {Shrinkage Clustering: a fast and size-constrained clustering algorithm for biomedical applications.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {19}, pmid = {29361928}, issn = {1471-2105}, support = {R01 GM106027/GM/NIGMS NIH HHS/United States ; CAREER 1150645//National Science Foundation/International ; R01 GM106027/NH/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Algorithms ; Brain/metabolism ; Breast Neoplasms/diagnosis ; Cluster Analysis ; Databases, Factual ; Female ; Gene Expression Regulation ; Humans ; Neoplasms/classification/genetics/pathology ; }, abstract = {BACKGROUND: Many common clustering algorithms require a two-step process that limits their efficiency. The algorithms need to be performed repetitively and need to be implemented together with a model selection criterion. These two steps are needed in order to determine both the number of clusters present in the data and the corresponding cluster memberships. As biomedical datasets increase in size and prevalence, there is a growing need for new methods that are more convenient to implement and are more computationally efficient. In addition, it is often essential to obtain clusters of sufficient sample size to make the clustering result meaningful and interpretable for subsequent analysis.

RESULTS: We introduce Shrinkage Clustering, a novel clustering algorithm based on matrix factorization that simultaneously finds the optimal number of clusters while partitioning the data. We report its performances across multiple simulated and actual datasets, and demonstrate its strength in accuracy and speed applied to subtyping cancer and brain tissues. In addition, the algorithm offers a straightforward solution to clustering with cluster size constraints.

CONCLUSIONS: Given its ease of implementation, computing efficiency and extensible structure, Shrinkage Clustering can be applied broadly to solve biomedical clustering tasks especially when dealing with large datasets.}, } @article {pmid29361913, year = {2018}, author = {Zhu, G and Li, W and Zhang, F and Guo, W}, title = {RNA-seq analysis reveals alternative splicing under salt stress in cotton, Gossypium davidsonii.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {73}, pmid = {29361913}, issn = {1471-2164}, support = {2016ZX08005-004//National Transgenic Program/International ; BE2015360//Key R D program in Jiangsu Province/International ; 2015-NY-002//Six talent peaks project in Jiangsu province/International ; No.10//JCIC-MCP project/International ; KYYJ201701//the Fundamental Research Funds for the Central Universities/International ; }, mesh = {*Alternative Splicing ; Gene Expression Profiling ; Gossypium/*genetics/metabolism ; RNA Isoforms/metabolism ; *Salinity ; Sequence Analysis, RNA ; Serine-Arginine Splicing Factors/genetics/metabolism ; Stress, Physiological/genetics ; }, abstract = {BACKGROUND: Numerous studies have focused on the regulation of gene expression in response to salt stress at the transcriptional level; however, little is known about this process at the post-transcriptional level.

RESULTS: Using a diploid D genome wild salinity-tolerant cotton species, Gossypium davidsonii, we analyzed alternative splicing (AS) of genes related to salt stress by comparing high-throughput transcriptomes from salt-treated and well-watered roots and leaves. A total of 14,172 AS events were identified involving 6798 genes, of which intron retention (35.73%) was the most frequent, being detected in 3492 genes. Under salt stress, 1287 and 1228 differential alternative splicing (DAS) events were identified in roots and leaves, respectively. These DAS genes were associated with specific functional pathways, such as "responses to stress", "metabolic process" and "RNA splicing", implying that AS represents an important pathway of gene regulation in response to salt stress. Several salt response genes, such as pyrroline-5-carboxylate synthase (P5CS), K+ channel outward (KCO1), plasma membrane intrinsic protein (PIP) and WRKY33 which were involved in osmotic balance, ion homeostasis, water transportation and transcriptional regulation, respectively, were identified with differential alternative splicing under salt stress. Moreover, we revealed that 13 genes encoding Ser/Arg-rich (SR) proteins related to AS regulation were differentially alternatively spliced under salt stress.

CONCLUSION: This study first provide a comprehensive view of AS in G. davidsonii, and highlight novel insights into the potential roles of AS in plant responses to salt stress.}, } @article {pmid29361909, year = {2018}, author = {Sivley, RM and Sheehan, JH and Kropski, JA and Cogan, J and Blackwell, TS and Phillips, JA and Bush, WS and Meiler, J and Capra, JA}, title = {Three-dimensional spatial analysis of missense variants in RTEL1 identifies pathogenic variants in patients with Familial Interstitial Pneumonia.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {18}, pmid = {29361909}, issn = {1471-2105}, support = {R01 GM099842/GM/NIGMS NIH HHS/United States ; P01 HL092870/HL/NHLBI NIH HHS/United States ; K08 HL130595/HL/NHLBI NIH HHS/United States ; U01HG007674/NH/NIH HHS/United States ; R01 GM080403/GM/NIGMS NIH HHS/United States ; T32 EY021453/EY/NEI NIH HHS/United States ; U01 HG007674/HG/NHGRI NIH HHS/United States ; U54 HL127672/HL/NHLBI NIH HHS/United States ; K08HL130595/HL/NHLBI NIH HHS/United States ; U54HL127672/HL/NHLBI NIH HHS/United States ; P01HL92870//National Heart, Lung, and Blood Institute (US)/International ; HL122010/HL/NHLBI NIH HHS/United States ; R01 HL085317/HL/NHLBI NIH HHS/United States ; R01 HL122010/HL/NHLBI NIH HHS/United States ; R01HL085317/HL/NHLBI NIH HHS/United States ; GM099842/GM/NIGMS NIH HHS/United States ; GM080403//National Institute of General Medical Sciences (US)/International ; Ambassadors Discovery Grant in Cancer Research//Vanderbilt-Ingram Cancer Center/International ; NIH T32 EY021453/EY/NEI NIH HHS/United States ; }, mesh = {*Algorithms ; Area Under Curve ; DNA Helicases/chemistry/*genetics/metabolism ; Humans ; Lung Diseases, Interstitial/genetics/*pathology ; Mutation, Missense ; Protein Structure, Tertiary ; ROC Curve ; *Spatial Analysis ; }, abstract = {BACKGROUND: Next-generation sequencing of individuals with genetic diseases often detects candidate rare variants in numerous genes, but determining which are causal remains challenging. We hypothesized that the spatial distribution of missense variants in protein structures contains information about function and pathogenicity that can help prioritize variants of unknown significance (VUS) and elucidate the structural mechanisms leading to disease.

RESULTS: To illustrate this approach in a clinical application, we analyzed 13 candidate missense variants in regulator of telomere elongation helicase 1 (RTEL1) identified in patients with Familial Interstitial Pneumonia (FIP). We curated pathogenic and neutral RTEL1 variants from the literature and public databases. We then used homology modeling to construct a 3D structural model of RTEL1 and mapped known variants into this structure. We next developed a pathogenicity prediction algorithm based on proximity to known disease causing and neutral variants and evaluated its performance with leave-one-out cross-validation. We further validated our predictions with segregation analyses, telomere lengths, and mutagenesis data from the homologous XPD protein. Our algorithm for classifying RTEL1 VUS based on spatial proximity to pathogenic and neutral variation accurately distinguished 7 known pathogenic from 29 neutral variants (ROC AUC = 0.85) in the N-terminal domains of RTEL1. Pathogenic proximity scores were also significantly correlated with effects on ATPase activity (Pearson r = -0.65, p = 0.0004) in XPD, a related helicase. Applying the algorithm to 13 VUS identified from sequencing of RTEL1 from patients predicted five out of six disease-segregating VUS to be pathogenic. We provide structural hypotheses regarding how these mutations may disrupt RTEL1 ATPase and helicase function.

CONCLUSIONS: Spatial analysis of missense variation accurately classified candidate VUS in RTEL1 and suggests how such variants cause disease. Incorporating spatial proximity analyses into other pathogenicity prediction tools may improve accuracy for other genes and genetic diseases.}, } @article {pmid29361908, year = {2018}, author = {Acharjee, A and Chibon, PY and Kloosterman, B and America, T and Renaut, J and Maliepaard, C and Visser, RGF}, title = {Genetical genomics of quality related traits in potato tubers using proteomics.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {20}, pmid = {29361908}, issn = {1471-2229}, mesh = {*Carbohydrate Metabolism ; Food Quality ; Genomics ; Phenotype ; Plant Tubers/genetics/*physiology ; Proteomics ; Solanum tuberosum/genetics/*physiology ; Starch/*metabolism ; }, abstract = {BACKGROUND: Recent advances in ~omics technologies such as transcriptomics, metabolomics and proteomics along with genotypic profiling have permitted the genetic dissection of complex traits such as quality traits in non-model species. To get more insight into the genetic factors underlying variation in quality traits related to carbohydrate and starch metabolism and cold sweetening, we determined the protein content and composition in potato tubers using 2D-gel electrophoresis in a diploid potato mapping population. Upon analyzing we made sure that the proteins from the patatin family were excluded to ensure a better representation of the other proteins.

RESULTS: We subsequently performed pQTL analyses for all other proteins with a sufficient representation in the population and established a relationship between proteins and 26 potato tuber quality traits (e.g. flesh colour, enzymatic discoloration) by co-localization on the genetic map and a direct correlation study of protein abundances and phenotypic traits. Over 1643 unique protein spots were detected in total over the two harvests. We were able to map pQTLs for over 300 different protein spots some of which co-localized with traits such as starch content and cold sweetening. pQTLs were observed on every chromosome although not evenly distributed over the chromosomes. The largest number of pQTLs was found for chromosome 8 and the lowest for chromosome number 10. For some 20 protein spots multiple QTLs were observed.

CONCLUSIONS: From this analysis, hotspot areas for protein QTLs were identified on chromosomes three, five, eight and nine. The hotspot on chromosome 3 coincided with a QTL previously identified for total protein content and had more than 23 pQTLs in the region from 70 to 80 cM. Some of the co-localizing protein spots associated with some of the most interesting tuber quality traits were identified, albeit far less than we had anticipated at the onset of the experiments.}, } @article {pmid29361907, year = {2018}, author = {Johnsson, M and Henriksen, R and Höglund, A and Fogelholm, J and Jensen, P and Wright, D}, title = {Genetical genomics of growth in a chicken model.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {72}, pmid = {29361907}, issn = {1471-2164}, support = {621-2011-4802//Vetenskapsrådet/International ; 221-2012-667//Svenska Forskningsrådet Formas/International ; 322206//European Research Council/International ; 12:546//Carl Tryggers Stiftelse för Vetenskaplig Forskning/International ; }, mesh = {Animals ; Body Mass Index ; Body Weight/genetics ; Chickens/*genetics/*growth & development ; Female ; Genomics ; Liver/metabolism ; Male ; Models, Genetic ; *Quantitative Trait Loci ; Transcriptome ; }, abstract = {BACKGROUND: The genetics underlying body mass and growth are key to understanding a wide range of topics in biology, both evolutionary and developmental. Body mass and growth traits are affected by many genetic variants of small effect. This complicates genetic mapping of growth and body mass. Experimental intercrosses between individuals from divergent populations allows us to map naturally occurring genetic variants for selected traits, such as body mass by linkage mapping. By simultaneously measuring traits and intermediary molecular phenotypes, such as gene expression, one can use integrative genomics to search for potential causative genes.

RESULTS: In this study, we use linkage mapping approach to map growth traits (N = 471) and liver gene expression (N = 130) in an advanced intercross of wild Red Junglefowl and domestic White Leghorn layer chickens. We find 16 loci for growth traits, and 1463 loci for liver gene expression, as measured by microarrays. Of these, the genes TRAK1, OSBPL8, YEATS4, CEP55, and PIP4K2B are identified as strong candidates for growth loci in the chicken. We also show a high degree of sex-specific gene-regulation, with almost every gene expression locus exhibiting sex-interactions. Finally, several trans-regulatory hotspots were found, one of which coincides with a major growth locus.

CONCLUSIONS: These findings not only serve to identify several strong candidates affecting growth, but also show how sex-specificity and local gene-regulation affect growth regulation in the chicken.}, } @article {pmid29361906, year = {2018}, author = {Yaish, MW and Al-Lawati, A and Al-Harrasi, I and Patankar, HV}, title = {Genome-wide DNA Methylation analysis in response to salinity in the model plant caliph medic (Medicago truncatula).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {78}, pmid = {29361906}, issn = {1471-2164}, mesh = {*DNA Methylation ; Epigenomics ; *Gene Expression Regulation, Plant ; *Genome, Plant ; Medicago truncatula/*genetics/growth & development ; *Models, Biological ; Molecular Sequence Annotation/methods ; Plant Roots/genetics/growth & development ; *Salinity ; Sequence Analysis, DNA ; Stress, Physiological ; }, abstract = {BACKGROUND: DNA methylation has a potential role in controlling gene expression and may, therefore, contribute to salinity adaptation in plants. Caliph medic (Medicago truncatula) is a model legume of moderate salinity tolerance capacity; however, a base-resolution DNA methylome map is not yet available for this plant.

RESULTS: In this report, a differential whole-genome bisulfite sequencing (WGBS) was carried out using DNA samples extracted from root tissues exposed to either control or saline conditions. Around 50 million differentially methylated sites (DMSs) were recognized, 7% of which were significantly (p < 0.05, FDR < 0.05) altered in response to salinity. This analysis showed that 77.0% of the contexts of DMSs were mCHH, while only 9.1% and 13.9% were mCHG and mCG, respectively. The average change in methylation level was increased in all sequence contexts, ranging from 3.8 to 10.2% due to salinity stress. However, collectively, the level of the DNA methylation in the gene body slightly decreased in response to salinity treatment. The global increase in DNA methylation due to salinity was confirmed by mass spectrometry analysis. Gene expression analysis using qPCR did not reveal a constant relationship between the level of mCG methylation and the transcription abundance of some genes of potential importance in salinity tolerance, such as the potassium channel KAT3, the vacuolar H+-pyrophosphatase (V-PPase), and the AP2/ERF and bZIP transcription factors, implying the involvement of other epigenetic gene expression controllers. Computational functional prediction of the annotated genes that embrace DMSs revealed the presence of enzymes with potential cellular functions in biological processes associated with salinity tolerance mechanisms.

CONCLUSIONS: The information obtained from this study illustrates the effect of salinity on DNA methylation and shows how plants can remodel the landscape of 5-methylcytosine nucleotide (5-mC) in the DNA across gene structures, in response to salinity. This remodeling varies between gene regions and between 5-mC sequence contexts. The mCG has a vague impact on the expression levels of a few selected potentially important genes in salt tolerant mechanisms.}, } @article {pmid29361905, year = {2018}, author = {Ruiz, C and Nadal, A and Foix, L and Montesinos, L and Montesinos, E and Pla, M}, title = {Diversity of plant defense elicitor peptides within the Rosaceae.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {11}, pmid = {29361905}, issn = {1471-2156}, mesh = {Peptides/*genetics/*immunology ; *Plant Immunity ; Plant Proteins/genetics/immunology ; Rosaceae/classification/*genetics/*immunology/microbiology ; }, abstract = {BACKGROUND: Plant elicitor peptides (Peps) are endogenous molecules that induce and amplify the first line of inducible plant defense, known as pattern-triggered immunity, contributing to protect plants against attack by bacteria, fungi and herbivores. Pep topic application and transgenic expression have been found to enhance disease resistance in a small number of model plant-pathogen systems. The action of Peps relies on perception by specific receptors, so displaying a family-specific activity. Recently, the presence and activity of Peps within the Rosaceae has been demonstrated. Here we characterized the population of Pep sequences within the economically important plant family of Rosaceae, with special emphasis on the Amygdaleae and Pyreae tribes, which include the most relevant edible species such as apple, pear and peach, and numerous ornamental and wild species (e.g. photinia, firethorn and hawthorn).

RESULTS: The systematic experimental search for Pep and the corresponding precursor PROPEP sequences within 36 Amygdaleae and Pyreae species, and 100 cultivars had a highly homogeneous pattern, with two tribe-specific Pep types per plant, i.e. Pep1 and Pep2 (Amygdaleae) or Pep3 and Pep4 (Pyreae). Pep2 and Pep3 are highly conserved, reaching identity percentages similar to those of genes used in plant phylogenetic analyses, while Pep1 and Pep4 are somewhat more variable, with similar values to the corresponding PROPEPs. In contrast to Pep3 and Pep4, Pep1 and Pep2 sequences of different species paralleled their phylogenetic relationships, and putative ancestor sequences were identified. The large amount of sequences allowed refining of a C-terminal consensus sequence that would support the protective activity of Pep1-4 in a Prunus spp. and Xanthomonas arboricola pv. pruni system. Moreover, tribe-specific consensus sequences were deduced at the center and C-terminal regions of Peps, which might explain the higher protection efficiencies described upon topic treatments with Peps from the same tribe.

CONCLUSIONS: The present study substantially enhances the knowledge on Peps within the Amygdaleae and Pyreae species. It can be the basis to design and fine-tune new control tools against important plant pathogens affecting Prunus, Pyrus and Malus species.}, } @article {pmid29361904, year = {2018}, author = {Hitch, TCA and Creevey, CJ}, title = {Spherical: an iterative workflow for assembling metagenomic datasets.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {20}, pmid = {29361904}, issn = {1471-2105}, support = {BB/E/W/10964A01//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Cecum/microbiology ; Chickens ; Groundwater/microbiology ; Humans ; Internet ; *Metagenome ; Mouth/microbiology ; *User-Computer Interface ; }, abstract = {BACKGROUND: The consensus emerging from the study of microbiomes is that they are far more complex than previously thought, requiring better assemblies and increasingly deeper sequencing. However, current metagenomic assembly techniques regularly fail to incorporate all, or even the majority in some cases, of the sequence information generated for many microbiomes, negating this effort. This can especially bias the information gathered and the perceived importance of the minor taxa in a microbiome.

RESULTS: We propose a simple but effective approach, implemented in Python, to address this problem. Based on an iterative methodology, our workflow (called Spherical) carries out successive rounds of assemblies with the sequencing reads not yet utilised. This approach also allows the user to reduce the resources required for very large datasets, by assembling random subsets of the whole in a "divide and conquer" manner.

CONCLUSIONS: We demonstrate the accuracy of Spherical using simulated data based on completely sequenced genomes and the effectiveness of the workflow at retrieving lost information for taxa in three published metagenomics studies of varying sizes. Our results show that Spherical increased the amount of reads utilized in the assembly by up to 109% compared to the base assembly. The additional contigs assembled by the Spherical workflow resulted in a significant (P < 0.05) changes in the predicted taxonomic profile of all datasets analysed. Spherical is implemented in Python 2.7 and freely available for use under the MIT license. Source code and documentation is hosted publically at: https://github.com/thh32/Spherical .}, } @article {pmid29361847, year = {2018}, author = {Polo, P and Fernandez, A and Muñoz-Reyes, JA and Dufey, M and Buunk, AP}, title = {Intrasexual Competition and Height in Adolescents and Adults.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704917749172}, doi = {10.1177/1474704917749172}, pmid = {29361847}, issn = {1474-7049}, mesh = {Adolescent ; Adult ; Body Height/*physiology ; Chile ; Competitive Behavior/*physiology ; Female ; Humans ; Male ; Middle Aged ; Sexual Behavior/physiology/*psychology ; Young Adult ; }, abstract = {Intrasexual competition can be defined as the struggle between members of one sex to increase their access to members of the other sex as sexual partners. In our species, height is a sexually dimorphic trait probably involved in both intrasexual and intersexual selective processes. In the present research, we examined the relationship between height and individual differences in intrasexual competitiveness (i.e., the tendency to view same-sex interactions in general in competitive terms) in two populations of adolescents and adults of both sexes in Chile. According to our first prediction, among both adolescent and adult men, height was negatively associated with intrasexual competitiveness. In contrast, among women, height was not linearly nor quadratically related with intrasexual competitiveness as previously reported. Finally, adolescent men and women showed increased levels of intrasexual competitiveness compared to adult same-sex counterparts. Our results suggest that height is a relevant trait in mating competition among men. The lack of relationship between height and intrasexual competitiveness in women may suggest that the role of height in women mating competition may be more complex and mediated by other variables.}, } @article {pmid29361313, year = {2018}, author = {Halushka, MK and Fromm, B and Peterson, KJ and McCall, MN}, title = {Big Strides in Cellular MicroRNA Expression.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {165-167}, pmid = {29361313}, issn = {0168-9525}, support = {R01 HL137811/HL/NHLBI NIH HHS/United States ; UL1 TR002001/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Eukaryotic Cells/cytology/metabolism ; Gene Expression Profiling/*methods ; *Gene Expression Regulation ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; MicroRNAs/*genetics ; Organ Specificity/genetics ; RNA, Messenger/genetics ; }, abstract = {A lack of knowledge of the cellular origin of miRNAs has greatly confounded functional and biomarkers studies. Recently, three studies characterized miRNA expression patterns across >78 human cell types. These combined data expand our knowledge of miRNA expression localization and confirm that many miRNAs show cell type-specific expression patterns.}, } @article {pmid29361159, year = {2018}, author = {Ramos-Morales, E and Rossi, G and Cattin, M and Jones, E and Braganca, R and Newbold, CJ}, title = {The effect of an isoflavonid-rich liquorice extract on fermentation, methanogenesis and the microbiome in the rumen simulation technique.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, pmid = {29361159}, issn = {1574-6941}, support = {BB/J0013/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Due to the antimicrobial activity of flavonoids, it has been suggested that they may provide a possible alternative to antibiotics to stimulate productivity and reduce the environmental load of ruminant agriculture. We hypothesised that an extract of liquorice, rich in prenylated isoflavonoids and particularly glabridin, might potentially improve the efficiency of nitrogen utilisation and reduce methane production in the rumen. When added to a long-term rumen simulating fermentor (RUSITEC), liquorice extract at 1 g L-1 decreased ammonia production (-51%; P < 0.001) without affecting the overall fermentation process. When added at 2 g L-1, decreases in not only ammonia production (-77%; P < 0.001), but also methane (-27%; P = 0.039) and total VFA production (-15%; P = 0.003) were observed. These effects in fermentation were probably related to a decrease in protozoa numbers, a less diverse bacteria population as well as changes in the structure of both the bacterial and archaeal communities. The inclusion of an isoflavonoid-rich extract from liquorice in the diet may potentially improve the efficiency of the feed utilisation by ruminants.}, } @article {pmid29361128, year = {2018}, author = {Wei, KH and Lower, SE and Caldas, IV and Sless, TJS and Barbash, DA and Clark, AG}, title = {Variable Rates of Simple Satellite Gains across the Drosophila Phylogeny.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {925-941}, pmid = {29361128}, issn = {1537-1719}, support = {R01 GM074737/GM/NIGMS NIH HHS/United States ; R01 GM119125/GM/NIGMS NIH HHS/United States ; }, abstract = {Simple satellites are tandemly repeating short DNA motifs that can span megabases in eukaryotic genomes. Because they can cause genomic instability through nonallelic homologous exchange, they are primarily found in the repressive heterochromatin near centromeres and telomeres where recombination is minimal, and on the Y chromosome, where they accumulate as the chromosome degenerates. Interestingly, the types and abundances of simple satellites often vary dramatically between closely related species, suggesting that they turn over rapidly. However, limited sampling has prevented detailed understanding of their evolutionary dynamics. Here, we characterize simple satellites from whole-genome sequences generated from males and females of nine Drosophila species, spanning 40 Ma of evolution. We show that PCR-free library preparation and postsequencing GC-correction better capture satellite quantities than conventional methods. We find that over half of the 207 simple satellites identified are species-specific, consistent with previous descriptions of their rapid evolution. Based on a maximum parsimony framework, we determined that most interspecific differences are due to lineage-specific gains. Simple satellites gained within a species are typically a single mutation away from abundant existing satellites, suggesting that they likely emerge from existing satellites, especially in the genomes of satellite-rich species. Interestingly, unlike most of the other lineages which experience various degrees of gains, the lineage leading up to the satellite-poor D. pseudoobscura and D. persimilis appears to be recalcitrant to gains, providing a counterpoint to the notion that simple satellites are universally rapidly evolving.}, } @article {pmid29361041, year = {2018}, author = {Ligat, G and Cazal, R and Hantz, S and Alain, S}, title = {The human cytomegalovirus terminase complex as an antiviral target: a close-up view.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {2}, pages = {137-145}, pmid = {29361041}, issn = {1574-6976}, mesh = {Antiviral Agents/administration & dosage/pharmacology ; Cytomegalovirus/drug effects/*enzymology ; Cytomegalovirus Infections/drug therapy ; *Drug Delivery Systems ; Endodeoxyribonucleases/*antagonists & inhibitors/metabolism ; }, abstract = {Human cytomegalovirus (HCMV) is responsible for life-threatening infections in immunocompromised individuals and can cause serious congenital malformations. Available antivirals target the viral polymerase but are subject to cross-resistance and toxicity. New antivirals targeting other replication steps and inducing fewer adverse effects are therefore needed. During HCMV replication, DNA maturation and packaging are performed by the terminase complex, which cleaves DNA to package the genome into the capsid. Identified in herpesviruses and bacteriophages, and with no counterpart in mammalian cells, these terminase proteins are ideal targets for highly specific antivirals. A new terminase inhibitor, letermovir, recently proved effective against HCMV in phase III clinical trials, but the mechanism of action is unclear. Letermovir has no significant activity against other herpesvirus or non-human CMV. This review focuses on the highly conserved mechanism of HCMV DNA-packaging and the potential of the terminase complex to serve as an antiviral target. We describe the intrinsic mechanism of DNA-packaging, highlighting the structure-function relationship of HCMV terminase complex components.}, } @article {pmid29361025, year = {2018}, author = {Smith, J and Coop, G and Stephens, M and Novembre, J}, title = {Estimating Time to the Common Ancestor for a Beneficial Allele.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {1003-1017}, pmid = {29361025}, issn = {1537-1719}, support = {R01 GM083098/GM/NIGMS NIH HHS/United States ; R01 GM108779/GM/NIGMS NIH HHS/United States ; R01 HG007089/HG/NHGRI NIH HHS/United States ; T32 GM007197/GM/NIGMS NIH HHS/United States ; }, abstract = {The haplotypes of a beneficial allele carry information about its history that can shed light on its age and the putative cause for its increase in frequency. Specifically, the signature of an allele's age is contained in the pattern of variation that mutation and recombination impose on its haplotypic background. We provide a method to exploit this pattern and infer the time to the common ancestor of a positively selected allele following a rapid increase in frequency. We do so using a hidden Markov model which leverages the length distribution of the shared ancestral haplotype, the accumulation of derived mutations on the ancestral background, and the surrounding background haplotype diversity. Using simulations, we demonstrate how the inclusion of information from both mutation and recombination events increases accuracy relative to approaches that only consider a single type of event. We also show the behavior of the estimator in cases where data do not conform to model assumptions, and provide some diagnostics for assessing and improving inference. Using the method, we analyze population-specific patterns in the 1000 Genomes Project data to estimate the timing of adaptation for several variants which show evidence of recent selection and functional relevance to diet, skin pigmentation, and morphology in humans.}, } @article {pmid29360978, year = {2018}, author = {Tollis, M and Hutchins, ED and Stapley, J and Rupp, SM and Eckalbar, WL and Maayan, I and Lasku, E and Infante, CR and Dennis, SR and Robertson, JA and May, CM and Crusoe, MR and Bermingham, E and DeNardo, DF and Hsieh, ST and Kulathinal, RJ and McMillan, WO and Menke, DB and Pratt, SC and Rawls, JA and Sanjur, O and Wilson-Rawls, J and Wilson Sayres, MA and Fisher, RE and Kusumi, K}, title = {Comparative Genomics Reveals Accelerated Evolution in Conserved Pathways during the Diversification of Anole Lizards.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {489-506}, pmid = {29360978}, issn = {1759-6653}, mesh = {Animals ; Biological Evolution ; DNA/genetics ; *Evolution, Molecular ; Genetic Variation ; Genomics ; Lizards/anatomy & histology/*genetics/physiology ; Molecular Sequence Annotation ; Phylogeny ; Selection, Genetic ; }, abstract = {Squamates include all lizards and snakes, and display some of the most diverse and extreme morphological adaptations among vertebrates. However, compared with birds and mammals, relatively few resources exist for comparative genomic analyses of squamates, hampering efforts to understand the molecular bases of phenotypic diversification in such a speciose clade. In particular, the ∼400 species of anole lizard represent an extensive squamate radiation. Here, we sequence and assemble the draft genomes of three anole species-Anolis frenatus, Anolis auratus, and Anolis apletophallus-for comparison with the available reference genome of Anolis carolinensis. Comparative analyses reveal a rapid background rate of molecular evolution consistent with a model of punctuated equilibrium, and strong purifying selection on functional genomic elements in anoles. We find evidence for accelerated evolution in genes involved in behavior, sensory perception, and reproduction, as well as in genes regulating limb bud development and hindlimb specification. Morphometric analyses of anole fore and hindlimbs corroborated these findings. We detect signatures of positive selection across several genes related to the development and regulation of the forebrain, hormones, and the iguanian lizard dewlap, suggesting molecular changes underlying behavioral adaptations known to reinforce species boundaries were a key component in the diversification of anole lizards.}, } @article {pmid29360975, year = {2018}, author = {Bridel, S and Olsen, AB and Nilsen, H and Bernardet, JF and Achaz, G and Avendaño-Herrera, R and Duchaud, E}, title = {Comparative Genomics of Tenacibaculum dicentrarchi and "Tenacibaculum finnmarkense" Highlights Intricate Evolution of Fish-Pathogenic Species.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {452-457}, pmid = {29360975}, issn = {1759-6653}, mesh = {Animals ; Fish Diseases/*microbiology ; Fishes/*microbiology ; Flavobacteriaceae Infections/*veterinary ; Genome, Bacterial ; Genomics ; Phylogeny ; Tenacibaculum/*genetics ; }, abstract = {The genus Tenacibaculum encompasses several species pathogenic for marine fish. Tenacibaculum dicentrarchi and "Tenacibaculum finnmarkense" (Quotation marks denote species that have not been validly named.) were retrieved from skin lesions of farmed fish such as European sea bass or Atlantic salmon. They cause a condition referred to as tenacibaculosis and severe outbreaks and important fish losses have been reported in Spanish, Norwegian, and Chilean marine farms. We report here the draft genomes of the T. dicentrarchi and "T. finnmarkense" type strains. These genomes were compared with draft genomes from field isolates retrieved from Chile and Norway and with previously published Tenacibaculum genomes. We used Average Nucleotide Identity and core genome-based phylogeny as a proxy index for species boundary delineation. This work highlights evolution of closely related fish-pathogenic species and suggests that homologous recombination likely contributes to genome evolution. It also corrects the species affiliation of strain AYD7486TD claimed by Grothusen et al. (2016).}, } @article {pmid29360967, year = {2018}, author = {Brown, MW and Heiss, AA and Kamikawa, R and Inagaki, Y and Yabuki, A and Tice, AK and Shiratori, T and Ishida, KI and Hashimoto, T and Simpson, AGB and Roger, AJ}, title = {Phylogenomics Places Orphan Protistan Lineages in a Novel Eukaryotic Super-Group.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {427-433}, pmid = {29360967}, issn = {1759-6653}, mesh = {Eukaryota/classification/*genetics ; Genomics/methods ; High-Throughput Nucleotide Sequencing ; *Phylogeny ; Transcriptome ; }, abstract = {Recent phylogenetic analyses position certain "orphan" protist lineages deep in the tree of eukaryotic life, but their exact placements are poorly resolved. We conducted phylogenomic analyses that incorporate deeply sequenced transcriptomes from representatives of collodictyonids (diphylleids), rigifilids, Mantamonas, and ancyromonads (planomonads). Analyses of 351 genes, using site-heterogeneous mixture models, strongly support a novel super-group-level clade that includes collodictyonids, rigifilids, and Mantamonas, which we name "CRuMs". Further, they robustly place CRuMs as the closest branch to Amorphea (including animals and fungi). Ancyromonads are strongly inferred to be more distantly related to Amorphea than are CRuMs. They emerge either as sister to malawimonads, or as a separate deeper branch. CRuMs and ancyromonads represent two distinct major groups that branch deeply on the lineage that includes animals, near the most commonly inferred root of the eukaryote tree. This makes both groups crucial in examinations of the deepest-level history of extant eukaryotes.}, } @article {pmid29360964, year = {2018}, author = {Capt, C and Renaut, S and Ghiselli, F and Milani, L and Johnson, NA and Sietman, BE and Stewart, DT and Breton, S}, title = {Deciphering the Link between Doubly Uniparental Inheritance of mtDNA and Sex Determination in Bivalves: Clues from Comparative Transcriptomics.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {577-590}, pmid = {29360964}, issn = {1759-6653}, mesh = {Animals ; Bivalvia/*genetics/*growth & development ; DNA, Mitochondrial/*genetics ; Female ; Genome, Mitochondrial ; Inheritance Patterns ; Male ; Mitochondria/genetics ; Sex Determination Processes ; Transcriptome ; }, abstract = {Bivalves exhibit an astonishing diversity of sexual systems and sex-determining mechanisms. They can be gonochoric, hermaphroditic or androgenetic, with both genetic and environmental factors known to determine or influence sex. One unique sex-determining system involving the mitochondrial genome has also been hypothesized to exist in bivalves with doubly uniparental inheritance (DUI) of mtDNA. However, the link between DUI and sex determination remains obscure. In this study, we performed a comparative gonad transcriptomics analysis for two DUI-possessing freshwater mussel species to better understand the mechanisms underlying sex determination and DUI in these bivalves. We used a BLAST reciprocal analysis to identify orthologs between Venustaconcha ellipsiformis and Utterbackia peninsularis and compared our results with previously published sex-specific bivalve transcriptomes to identify conserved sex-determining genes. We also compared our data with other DUI species to identify candidate genes possibly involved in the regulation of DUI. A total of ∼12,000 orthologous relationships were found, with 2,583 genes differentially expressed in both species. Among these genes, key sex-determining factors previously reported in vertebrates and in bivalves (e.g., Sry, Dmrt1, Foxl2) were identified, suggesting that some steps of the sex-determination pathway may be deeply conserved in metazoans. Our results also support the hypothesis that a modified ubiquitination mechanism could be responsible for the retention of the paternal mtDNA in male bivalves, and revealed that DNA methylation could also be involved in the regulation of DUI. Globally, our results suggest that sets of genes associated with sex determination and DUI are similar in distantly-related DUI species.}, } @article {pmid29360963, year = {2018}, author = {Giguere, AT and Taylor, AE and Myrold, DD and Mellbye, BL and Sayavedra-Soto, LA and Bottomley, PJ}, title = {Nitrite-oxidizing activity responds to nitrite accumulation in soil.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy008}, pmid = {29360963}, issn = {1574-6941}, abstract = {The factors influencing how soil nitrite (NO2-)- and ammonia (NH3)-oxidizing activities remain coupled are unknown. A short-term study (<48 h) was conducted to examine the dynamics of NO2--oxidizing activity and the accumulation of NO2- in three Oregon soils stimulated by the addition of 1 mM NH4+ in soil slurry. Nitrite initially accumulated in all three soils; its subsequent decline or slowing of the accumulation of the NO2- pool by 24 h was accompanied by an increase in the size of the nitrate (NO3-) pool, indicating a change in NO2- oxidation kinetics. Bacterial protein synthesis inhibitors prevented the NO2- pool decline, resulting in a larger accumulation in all three soils. Although no significant increases in NO2--oxidizing bacteria nxrA (Nitrobacter) and nxrB (Nitrospira) gene abundances were detected over the time course, maximum NO2- consumption rates increased 2-fold in the treatment without antibiotics compared to no change with antibiotics. No changes were observed in the apparent half saturation constant (Km) values for NO2- consumption. This study demonstrates phenotypic flexibility among soil NO2- oxidizers, which can undergo protein synthesis-dependent increases in NO2- consumption rates to match NH3 oxidation rates and recouple nitrification.}, } @article {pmid29360961, year = {2018}, author = {McKinney, CW and Dungan, RS and Moore, A and Leytem, AB}, title = {Occurrence and abundance of antibiotic resistance genes in agricultural soil receiving dairy manure.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy010}, pmid = {29360961}, issn = {1574-6941}, abstract = {Animal manures are commonly used to enhance soil fertility, but there are growing concerns over the impact of this practice on the development and dissemination of antibiotic resistance. The aim of this field study was to determine the effect of annual dairy manure applications on the occurrence and abundance of antibiotic resistance genes (ARGs) in an agricultural soil during four years of crop production. Treatments included (i) control (no fertilizer or manure), (ii) inorganic fertilizer and (iii) dairy manure at three application rates. Quantitative PCR was used to determine absolute (per g dry soil) and relative (per 16S rRNA gene) abundances of ARGs in DNA extracted from soils. Six ARGs and one class 1 integron were targeted. This study found that (i) manure application increases ARG abundances above background soil levels; (ii) the higher the manure application rate, the higher the ARG abundance in soil; (iii) the amount of manure applied is more important than reoccurring annual applications of the same amount of manure; (iv) absolute abundance and occurrence of ARGs decreases with increasing soil depth, but relative abundances remained constant. This study demonstrated that dairy manure applications to soil significantly increase the abundance of clinically relevant ARGs when compared to control and inorganic fertilized plots.}, } @article {pmid29360960, year = {2018}, author = {Shi, X and Li, S and Liu, C and Zhang, M and Liu, M}, title = {Community structure of photosynthetic picoeukaryotes differs in lakes with different trophic statuses along the middle-lower reaches of the Yangtze River.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, doi = {10.1093/femsec/fiy011}, pmid = {29360960}, issn = {1574-6941}, abstract = {Photosynthetic picoeukaryotes (PPEs) play an important role in aquatic ecosystem functioning. There is still a relative lack of information on freshwater PPEs, especially in eutrophic lakes. We used a combination of flow cytometric sorting and pyrosequencing to investigate the PPEs community structure in more than 20 mesotrophic and eutrophic lakes along the middle-lower reaches of the Yangtze River in China. The abundance of PPEs ranged between 2.04 × 103 and 5.92 × 103 cells mL-1. The contribution of PPEs to total picophytoplankton abundance was generally higher in eutrophic lakes than in mesotrophic lakes. The sequencing results indicated that the Shannon diversity of PPEs was significantly higher in mesotrophic lakes than in eutrophic lakes. At the class level, PPEs were mainly dominated by three taxonomic groups, including Cryptophyceae, Coscinodiscophyceae and Chlorophyceae, and 15 additional known phytoplankton classes, including Synurophyceae, Dinophyceae, Chrysophyceae, Trebouxiophyceae and Prymnesiophyceae, were identified. Coscinodiscophyceae dominated in the most eutrophic lakes, while Chrysophyceae, Dinophyceae and other classes of PPEs were more abundant in the mesotrophic lakes. We also observed several PPEs operational taxonomic units, and those affiliated with Cyclotella atomus, Chlamydomonas sp. and Poterioochromonas malhamensis tended to be more prevalent in the eutrophic lakes. The canonical correspondence analysis and Mantel analysis highlighted the importance of environmental parameters as key drivers of PPEs community composition.}, } @article {pmid29360959, year = {2018}, author = {Jaquiéry, J and Peccoud, J and Ouisse, T and Legeai, F and Prunier-Leterme, N and Gouin, A and Nouhaud, P and Brisson, JA and Bickel, R and Purandare, S and Poulain, J and Battail, C and Lemaitre, C and Mieuzet, L and Le Trionnaire, G and Simon, JC and Rispe, C}, title = {Disentangling the Causes for Faster-X Evolution in Aphids.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {507-520}, pmid = {29360959}, issn = {1759-6653}, mesh = {Animals ; Aphids/*genetics/physiology ; Biological Evolution ; *Chromosomes, Insect ; *Evolution, Molecular ; Female ; Gene Expression Profiling ; Genes, X-Linked ; Genetic Drift ; Genome, Insect ; Male ; Polymorphism, Genetic ; Reproduction ; Reproduction, Asexual ; Sex Chromosomes/genetics ; X Chromosome/*genetics ; }, abstract = {The faster evolution of X chromosomes has been documented in several species, and results from the increased efficiency of selection on recessive alleles in hemizygous males and/or from increased drift due to the smaller effective population size of X chromosomes. Aphids are excellent models for evaluating the importance of selection in faster-X evolution because their peculiar life cycle and unusual inheritance of sex chromosomes should generally lead to equivalent effective population sizes for X and autosomes. Because we lack a high-density genetic map for the pea aphid, whose complete genome has been sequenced, we first assigned its entire genome to the X or autosomes based on ratios of sequencing depth in males (X0) to females (XX). Then, we computed nonsynonymous to synonymous substitutions ratios (dN/dS) for the pea aphid gene set and found faster evolution of X-linked genes. Our analyses of substitution rates, together with polymorphism and expression data, showed that relaxed selection is likely to be the greatest contributor to faster-X because a large fraction of X-linked genes are expressed at low rates and thus escape selection. Yet, a minor role for positive selection is also suggested by the difference between substitution rates for X and autosomes for male-biased genes (but not for asexual female-biased genes) and by lower Tajima's D for X-linked compared with autosomal genes with highly male-biased expression patterns. This study highlights the relevance of organisms displaying alternative chromosomal inheritance to the understanding of forces shaping genome evolution.}, } @article {pmid29360618, year = {2018}, author = {Yan, M and Fritsch, PW and Moore, MJ and Feng, T and Meng, A and Yang, J and Deng, T and Zhao, C and Yao, X and Sun, H and Wang, H}, title = {Plastid phylogenomics resolves infrafamilial relationships of the Styracaceae and sheds light on the backbone relationships of the Ericales.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {198-211}, doi = {10.1016/j.ympev.2018.01.004}, pmid = {29360618}, issn = {1095-9513}, mesh = {Base Sequence ; Ericales/*classification ; Evolution, Molecular ; Genome, Plastid ; *Genomics ; Introns/genetics ; Likelihood Functions ; *Phylogeny ; Plastids/*genetics ; Polymorphism, Single Nucleotide/genetics ; Repetitive Sequences, Nucleic Acid/genetics ; Styracaceae/*classification/*genetics ; }, abstract = {Relationships among the genera of the small, woody family Styracaceae and among families of the large, diverse order Ericales have resisted complete resolution with sequences from one or a few genes. We used plastome sequencing to attempt to resolve the backbone relationships of Styracaceae and Ericales and to explore plastome structural evolution. Complete plastomes for 23 species are newly reported here, including 18 taxa of Styracaceae and five of Ericales (including species of Sapotaceae, Clethraceae, Symplocaceae, and Diapensiaceae). Combined with publicly available complete plastome data, this resulted in a data set of 60 plastomes, including 11 of the 12 genera of Styracaceae and 12 of 22 families of Ericales. Styracaceae plastomes were found to possess the quadripartite structure typical of angiosperms, with sizes ranging from 155 to 159 kb. Most of the plastomes were found to possess the full complement of typical angiosperm plastome genes. Unusual structural features were detected in plastomes of Alniphyllum and Bruinsmia, including the presence of a large 20-kb inversion (14 genes) in the Large Single-Copy region, the loss or pseudogenization of the clpP and accD genes in Bruinsmia, and the loss of the first exon of rps16 in B. styracoides. Likewise, the second intron from clpP was found to be lost in Alniphyllum and Huodendron. Phylogenomic analyses including all 79 plastid protein-coding genes provided improved resolution for relationships among the genera of Styracaceae and families of Ericales. Styracaceae was strongly supported as monophyletic, with Styrax, Huodendron, and a clade of Alniphyllum + Bruinsmia successively sister to the remainder of the family, all with strong support. All genera of Styracaceae were recovered as monophyletic, except for Halesia and Pterostyrax, which were each recovered as polyphyletic with strong support. Within Ericales, all families were recovered as monophyletic with strong support, with Balsaminaceae sister to remaining Ericales. Most relationships recovered in plastome analyses are congruent with previous analyses based on smaller data sets. Our results demonstrate the power of plastid phylogenomics to improve phylogenetic hypotheses among genera and families, and provide new insight into plastome evolution across Ericales.}, } @article {pmid29360617, year = {2018}, author = {Simon, A and Goffinet, B and Magain, N and Sérusiaux, E}, title = {High diversity, high insular endemism and recent origin in the lichen genus Sticta (lichenized Ascomycota, Peltigerales) in Madagascar and the Mascarenes.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {15-28}, doi = {10.1016/j.ympev.2018.01.012}, pmid = {29360617}, issn = {1095-9513}, mesh = {Ascomycota/*classification/genetics ; Biodiversity ; Biological Evolution ; DNA, Mitochondrial/chemistry/classification/genetics ; Fungal Proteins/chemistry/classification/genetics ; Haplotypes ; Madagascar ; Phylogeny ; RNA Polymerase II/chemistry/classification/genetics ; }, abstract = {Lichen biodiversity and its generative evolutionary processes are practically unknown in the MIOI (Madagascar and Indian Ocean Islands) biodiversity hotspot. We sought to test the hypothesis that lichenized fungi in this region have undergone a rapid radiation, following a single colonization event, giving rise to narrow endemics, as is characteristic of other lineages of plants. We extensively sampled specimens of the lichen genus Sticta in the Mascarene archipelago (mainly Réunion) and in Madagascar, mainly in the northern range (Amber Mt and Marojejy Mt) and produced the fungal ITS barcode sequence for 148 thalli. We further produced a four-loci data matrix for 68 of them, representing the diversity and geographical distribution of ITS haplotypes. We reconstructed the phylogenetic relationships within this group, established species boundaries with morphological context, and estimated the date of the most recent common ancestor. Our inferences resolve a robust clade comprising 31 endemic species of Sticta that arose from the diversification following a single recent (c. 11 Mya) colonization event. All but three species have a very restricted range, endemic to either the Mascarene archipelago or a single massif in Madagascar. The first genus of lichens to be studied with molecular data in this region underwent a recent radiation, exhibits micro-endemism, and thus exemplifies the biodiversity characteristics found in other taxa in Madagascar and the Mascarenes.}, } @article {pmid29360434, year = {2018}, author = {Niethamer, TK and Bush, JO}, title = {Getting direction(s): The Eph/ephrin signaling system in cell positioning.}, journal = {Developmental biology}, volume = {}, number = {}, pages = {}, pmid = {29360434}, issn = {1095-564X}, support = {F31 DE026059/DE/NIDCR NIH HHS/United States ; R01 DE023337/DE/NIDCR NIH HHS/United States ; R01 DE025877/DE/NIDCR NIH HHS/United States ; R21 DE025923/DE/NIDCR NIH HHS/United States ; }, abstract = {In vertebrates, the Eph/ephrin family of signaling molecules is a large group of membrane-bound proteins that signal through a myriad of mechanisms and effectors to play diverse roles in almost every tissue and organ system. Though Eph/ephrin signaling has functions in diverse biological processes, one core developmental function is in the regulation of cell position and tissue morphology by regulating cell migration and guidance, cell segregation, and boundary formation. Often, the role of Eph/ephrin signaling is to translate patterning information into physical movement of cells and changes in morphology that define tissue and organ systems. In this review, we focus on recent advances in the regulation of these processes, and our evolving understanding of the in vivo signaling mechanisms utilized in distinct developmental contexts.}, } @article {pmid29360433, year = {2018}, author = {Dineen, A and Osborne Nishimura, E and Goszczynski, B and Rothman, JH and McGhee, JD}, title = {Quantitating transcription factor redundancy: The relative roles of the ELT-2 and ELT-7 GATA factors in the C. elegans endoderm.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {150-161}, doi = {10.1016/j.ydbio.2017.12.023}, pmid = {29360433}, issn = {1095-564X}, support = {R01 HD081266/HD/NICHD NIH HHS/United States ; R01 HD082347/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/embryology/*genetics/growth & development ; Caenorhabditis elegans Proteins/genetics/*physiology ; Cell Differentiation ; Endoderm/*metabolism ; GATA Transcription Factors/deficiency/genetics/*physiology ; *Gene Expression Regulation, Developmental ; Genes, Helminth ; Genes, Reporter ; Genetic Association Studies ; Intestinal Mucosa/*metabolism ; Intestines/cytology ; Larva ; Promoter Regions, Genetic ; Transcription, Genetic ; Transcriptome ; }, abstract = {The two GATA transcription factors ELT-2 and ELT-7 function in the differentiation of the C. elegans intestine. ELT-2 loss causes lethality. ELT-7 loss causes no obvious phenotype but enhances the elt-2(-) intestinal phenotype. Thus, ELT-2 and ELT-7 appear partially redundant, with ELT-2 being more influential. To investigate the different regulatory roles of ELT-2 and ELT-7, we compared the transcriptional profiles of pure populations of wild-type, elt-2(-), elt-7(-), and elt-7(-); elt-2(-) double mutant L1-stage larvae. Consistent with the mutant phenotypes, loss of ELT-2 had a>25 fold greater influence on the number of significantly altered transcripts compared to the loss of ELT-7; nonetheless, the levels of numerous transcripts changed upon loss of ELT-7 in the elt-2(-) background. The quantitative responses of individual genes revealed a more complicated behaviour than simple redundancy/partial redundancy. In particular, genes expressed only in the intestine showed three distinguishable classes of response in the different mutant backgrounds. One class of genes responded as if ELT-2 is the major transcriptional activator and ELT-7 provides variable compensatory input. For a second class, transcript levels increased upon loss of ELT-2 but decreased upon further loss of ELT-7, suggesting that ELT-7 actually overcompensates for the loss of ELT-2. For a third class, transcript levels also increased upon loss of ELT-2 but remained elevated upon further loss of ELT-7, suggesting overcompensation by some other intestinal transcription factor(s). In spite of its minor loss-of-function phenotype and its limited sequence similarity to ELT-2, ELT-7 expressed under control of the elt-2 promoter is able to rescue elt-2(-) lethality. Indeed, appropriately expressed ELT-7, like appropriately expressed ELT-2, is able to replace all other core GATA factors in the C. elegans endodermal pathway. Overall, this study focuses attention on the quantitative intricacies behind apparent redundancy or partial redundancy of two related transcription factors.}, } @article {pmid29360179, year = {2018}, author = {Allman, BE and Weissman, DB}, title = {Hitchhiking in space: Ancestry in adapting, spatially extended populations.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {4}, pages = {722-734}, doi = {10.1111/evo.13431}, pmid = {29360179}, issn = {1558-5646}, support = {R25 GM099644/GM/NIGMS NIH HHS/United States ; }, abstract = {Selective sweeps reduce neutral genetic diversity. In sexual populations, this "hitchhiking" effect is thought to be limited to the local genomic region of the sweeping allele. While this is true in panmictic populations, we find that in spatially extended populations the combined effects of many unlinked sweeps can affect patterns of ancestry (and therefore neutral genetic diversity) across the whole genome. Even low rates of sweeps can be enough to skew the spatial locations of ancestors such that neutral mutations that occur in an individual living outside a small region in the center of the range have virtually no chance of fixing in the population. The fact that nearly all ancestry rapidly traces back to a small spatial region also means that relatedness between individuals falls off very slowly as a function of the spatial distance between them.}, } @article {pmid29359333, year = {2018}, author = {Mazer, SJ and Hendrickson, BT and Chellew, JP and Kim, LJ and Liu, JW and Shu, J and Sharma, MV}, title = {Divergence in pollen performance between Clarkia sister species with contrasting mating systems supports predictions of sexual selection.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {453-472}, doi = {10.1111/evo.13429}, pmid = {29359333}, issn = {1558-5646}, abstract = {Animal taxa that differ in the intensity of sperm competition often differ in sperm production or swimming speed, arguably due to sexual selection on postcopulatory male traits affecting siring success. In plants, closely related self- and cross-pollinated taxa similarly differ in the opportunity for sexual selection among male gametophytes after pollination, so traits such as the proportion of pollen on the stigma that rapidly enters the style and mean pollen tube growth rate (PTGR) are predicted to diverge between them. To date, no studies have tested this prediction in multiple plant populations under uniform conditions. We tested for differences in pollen performance in greenhouse-raised populations of two Clarkia sister species: the predominantly outcrossing C. unguiculata and the facultatively self-pollinating C. exilis. Within populations of each taxon, groups of individuals were reciprocally pollinated (n = 1153 pollinations) and their styles examined four hours later. We tested for the effects of species, population, pollen type (self vs. outcross), the number of competing pollen grains, and temperature on pollen performance. Clarkia unguiculata exhibited higher mean PTGR than C. exilis; pollen type had no effect on performance in either taxon. The difference between these species in PTGR is consistent with predictions of sexual selection theory.}, } @article {pmid29359326, year = {2018}, author = {Villamil, CI}, title = {Phenotypic integration of the cervical vertebrae in the Hominoidea (Primates).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {490-517}, doi = {10.1111/evo.13433}, pmid = {29359326}, issn = {1558-5646}, abstract = {Phenotypic integration and modularity represent important factors influencing evolutionary change. The mammalian cervical vertebral column is particularly interesting in regards to integration and modularity because it is highly constrained to seven elements, despite widely variable morphology. Previous research has found a common pattern of integration among quadrupedal mammals, but integration patterns also evolve in response to locomotor selective pressures like those associated with hominin bipedalism. Here, I test patterns of covariation in the cervical vertebrae of three hominoid primates (Hylobates, Pan, Homo) who engage in upright postures and locomotion. Patterns of integration in the hominoid cervical vertebrae correspond generally to those previously found in other mammals, suggesting that integration in this region is highly conserved, even among taxa that engage in novel positional behaviors. These integration patterns reflect underlying developmental as well as functional modules. The strong integration between vertebrae suggests that the functional morphology of the cervical vertebral column should be considered as a whole, rather than in individual vertebrae. Taxa that display highly derived morphologies in the cervical vertebrae are likely exploiting these integration patterns, rather than reorganizing them. Future work on vertebrates without cervical vertebral number constraints will further clarify the evolution of integration in this region.}, } @article {pmid29358742, year = {2018}, author = {Gurevich, A and Mikheenko, A and Shlemov, A and Korobeynikov, A and Mohimani, H and Pevzner, PA}, title = {Increased diversity of peptidic natural products revealed by modification-tolerant database search of mass spectra.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {319-327}, pmid = {29358742}, issn = {2058-5276}, support = {P41 GM103484/GM/NIGMS NIH HHS/United States ; }, abstract = {Peptidic natural products (PNPs) include many antibiotics and other bioactive compounds. While the recent launch of the Global Natural Products Social (GNPS) molecular networking infrastructure is transforming PNP discovery into a high-throughput technology, PNP identification algorithms are needed to realize the potential of the GNPS project. GNPS relies on the assumption that each connected component of a molecular network (representing related metabolites) illuminates the 'dark matter of metabolomics' as long as it contains a known metabolite present in a database. We reveal a surprising diversity of PNPs produced by related bacteria and show that, contrary to the 'comparative metabolomics' assumption, two related bacteria are unlikely to produce identical PNPs (even though they are likely to produce similar PNPs). Since this observation undermines the utility of GNPS, we developed a PNP identification tool, VarQuest, that illuminates the connected components in a molecular network even if they do not contain known PNPs and only contain their variants. VarQuest reveals an order of magnitude more PNP variants than all previous PNP discovery efforts and demonstrates that GNPS already contains spectra from 41% of the currently known PNP families. The enormous diversity of PNPs suggests that biosynthetic gene clusters in various microorganisms constantly evolve to generate a unique spectrum of PNP variants that differ from PNPs in other species.}, } @article {pmid29358741, year = {2018}, author = {Zoll, S and Lane-Serff, H and Mehmood, S and Schneider, J and Robinson, CV and Carrington, M and Higgins, MK}, title = {The structure of serum resistance-associated protein and its implications for human African trypanosomiasis.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {295-301}, doi = {10.1038/s41564-017-0085-3}, pmid = {29358741}, issn = {2058-5276}, abstract = {Only two trypanosome subspecies are able to cause human African trypanosomiasis. To establish an infection in human blood, they must overcome the innate immune system by resisting the toxic effects of trypanolytic factor 1 and trypanolytic factor 2 (refs. 1,2). These lipoprotein complexes contain an active, pore-forming component, apolipoprotein L1 (ApoL1), that causes trypanosome cell death 3 . One of the two human-infective subspecies, Trypanosoma brucei rhodesiense, differs from non-infective trypanosomes solely by the presence of the serum resistance-associated protein, which binds directly to ApoL1 and blocks its pore-forming capacity3-5. Since this interaction is the single critical event that renders T. b. rhodesiense human- infective, detailed structural information that allows identification of binding determinants is crucial to understand immune escape by the parasite. Here, we present the structure of serum resistance-associated protein and reveal the adaptations that occurred as it diverged from other trypanosome surface molecules to neutralize ApoL1. We also present our mapping of residues important for ApoL1 binding, giving molecular insight into this interaction at the heart of human sleeping sickness.}, } @article {pmid29358683, year = {2018}, author = {Mullineaux-Sanders, C and Suez, J and Elinav, E and Frankel, G}, title = {Sieving through gut models of colonization resistance.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {132-140}, doi = {10.1038/s41564-017-0095-1}, pmid = {29358683}, issn = {2058-5276}, abstract = {The development of innovative high-throughput genomics and metabolomics technologies has considerably expanded our understanding of the commensal microorganisms residing within the human body, collectively termed the microbiota. In recent years, the microbiota has been reported to have important roles in multiple aspects of human health, pathology and host-pathogen interactions. One function of commensals that has attracted particular interest is their role in protection against pathogens and pathobionts, a concept known as colonization resistance. However, pathogens are also able to sense and exploit the microbiota during infection. Therefore, obtaining a holistic understanding of colonization resistance mechanisms is essential for the development of microbiome-based and microbiome-targeting therapies for humans and animals. Achieving this is dependent on utilizing physiologically relevant animal models. In this Perspective, we discuss the colonization resistance functions of the gut microbiota and sieve through the advantages and limitations of murine models commonly used to study such mechanisms within the context of enteric bacterial infection.}, } @article {pmid29358682, year = {2018}, author = {Bieniasz, PD}, title = {A multimodal antiretroviral protein.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {122-123}, doi = {10.1038/s41564-017-0104-4}, pmid = {29358682}, issn = {2058-5276}, } @article {pmid29358681, year = {2018}, author = {Bourdoulous, S and Lemichez, E}, title = {Decoding glycan recognition by bacterial toxins.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {124-126}, doi = {10.1038/s41564-018-0107-9}, pmid = {29358681}, issn = {2058-5276}, } @article {pmid29358680, year = {2018}, author = {Mackie, RI and Cann, I}, title = {Let them eat fruit.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {127-129}, doi = {10.1038/s41564-018-0108-8}, pmid = {29358680}, issn = {2058-5276}, } @article {pmid29358679, year = {2018}, author = {Williamson, KC and Levine, RL and Miller, LH}, title = {Even malaria parasites watch their host's diet.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {130-131}, doi = {10.1038/s41564-017-0105-3}, pmid = {29358679}, issn = {2058-5276}, support = {R01 AI069314/AI/NIAID NIH HHS/United States ; }, } @article {pmid29358678, year = {2018}, author = {}, title = {Microbiology needs champions on-screen.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {121}, doi = {10.1038/s41564-018-0112-z}, pmid = {29358678}, issn = {2058-5276}, } @article {pmid29358654, year = {2018}, author = {Donaghey, J and Thakurela, S and Charlton, J and Chen, JS and Smith, ZD and Gu, H and Pop, R and Clement, K and Stamenova, EK and Karnik, R and Kelley, DR and Gifford, CA and Cacchiarelli, D and Rinn, JL and Gnirke, A and Ziller, MJ and Meissner, A}, title = {Genetic determinants and epigenetic effects of pioneer-factor occupancy.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {250-258}, doi = {10.1038/s41588-017-0034-3}, pmid = {29358654}, issn = {1546-1718}, support = {RM1 HG006193/HG/NHGRI NIH HHS/United States ; }, abstract = {Transcription factors (TFs) direct developmental transitions by binding to target DNA sequences, influencing gene expression and establishing complex gene-regultory networks. To systematically determine the molecular components that enable or constrain TF activity, we investigated the genomic occupancy of FOXA2, GATA4 and OCT4 in several cell types. Despite their classification as pioneer factors, all three TFs exhibit cell-type-specific binding, even when supraphysiologically and ectopically expressed. However, FOXA2 and GATA4 can be distinguished by low enrichment at loci that are highly occupied by these factors in alternative cell types. We find that expression of additional cofactors increases enrichment at a subset of these sites. Finally, FOXA2 occupancy and changes to DNA accessibility can occur in G1-arrested cells, but subsequent loss of DNA methylation requires DNA replication.}, } @article {pmid29358653, year = {2018}, author = {Guo, J and Xu, C and Wu, D and Zhao, Y and Qiu, Y and Wang, X and Ouyang, Y and Cai, B and Liu, X and Jing, S and Shangguan, X and Wang, H and Ma, Y and Hu, L and Wu, Y and Shi, S and Wang, W and Zhu, L and Xu, X and Chen, R and Feng, Y and Du, B and He, G}, title = {Bph6 encodes an exocyst-localized protein and confers broad resistance to planthoppers in rice.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {297-306}, doi = {10.1038/s41588-018-0039-6}, pmid = {29358653}, issn = {1546-1718}, abstract = {The brown planthopper (BPH) and white-backed planthopper (WBPH) are the most destructive insect pests of rice, and they pose serious threats to rice production throughout Asia. Thus, there are urgent needs to identify resistance-conferring genes and to breed planthopper-resistant rice varieties. Here we report the map-based cloning and functional analysis of Bph6, a gene that confers resistance to planthoppers in rice. Bph6 encodes a previously uncharacterized protein that localizes to exocysts and interacts with the exocyst subunit OsEXO70E1. Bph6 expression increases exocytosis and participates in cell wall maintenance and reinforcement. A coordinated cytokinin, salicylic acid and jasmonic acid signaling pathway is activated in Bph6-carrying plants, which display broad resistance to all tested BPH biotypes and to WBPH without sacrificing yield, as these plants were found to maintain a high level of performance in a field that was heavily infested with BPH. Our results suggest that a superior resistance gene that evolved long ago in a region where planthoppers are found year round could be very valuable for controlling agricultural insect pests.}, } @article {pmid29358652, year = {2018}, author = {Smith, JJ and Timoshevskaya, N and Ye, C and Holt, C and Keinath, MC and Parker, HJ and Cook, ME and Hess, JE and Narum, SR and Lamanna, F and Kaessmann, H and Timoshevskiy, VA and Waterbury, CKM and Saraceno, C and Wiedemann, LM and Robb, SMC and Baker, C and Eichler, EE and Hockman, D and Sauka-Spengler, T and Yandell, M and Krumlauf, R and Elgar, G and Amemiya, CT}, title = {The sea lamprey germline genome provides insights into programmed genome rearrangement and vertebrate evolution.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {270-277}, pmid = {29358652}, issn = {1546-1718}, support = {F32 GM087919/GM/NIGMS NIH HHS/United States ; R01 GM104123/GM/NIGMS NIH HHS/United States ; }, abstract = {The sea lamprey (Petromyzon marinus) serves as a comparative model for reconstructing vertebrate evolution. To enable more informed analyses, we developed a new assembly of the lamprey germline genome that integrates several complementary data sets. Analysis of this highly contiguous (chromosome-scale) assembly shows that both chromosomal and whole-genome duplications have played significant roles in the evolution of ancestral vertebrate and lamprey genomes, including chromosomes that carry the six lamprey HOX clusters. The assembly also contains several hundred genes that are reproducibly eliminated from somatic cells during early development in lamprey. Comparative analyses show that gnathostome (mouse) homologs of these genes are frequently marked by polycomb repressive complexes (PRCs) in embryonic stem cells, suggesting overlaps in the regulatory logic of somatic DNA elimination and bivalent states that are regulated by early embryonic PRCs. This new assembly will enhance diverse studies that are informed by lampreys' unique biology and evolutionary/comparative perspective.}, } @article {pmid29358651, year = {2018}, author = {Stein, JC and Yu, Y and Copetti, D and Zwickl, DJ and Zhang, L and Zhang, C and Chougule, K and Gao, D and Iwata, A and Goicoechea, JL and Wei, S and Wang, J and Liao, Y and Wang, M and Jacquemin, J and Becker, C and Kudrna, D and Zhang, J and Londono, CEM and Song, X and Lee, S and Sanchez, P and Zuccolo, A and Ammiraju, JSS and Talag, J and Danowitz, A and Rivera, LF and Gschwend, AR and Noutsos, C and Wu, CC and Kao, SM and Zeng, JW and Wei, FJ and Zhao, Q and Feng, Q and El Baidouri, M and Carpentier, MC and Lasserre, E and Cooke, R and Rosa Farias, DD and da Maia, LC and Dos Santos, RS and Nyberg, KG and McNally, KL and Mauleon, R and Alexandrov, N and Schmutz, J and Flowers, D and Fan, C and Weigel, D and Jena, KK and Wicker, T and Chen, M and Han, B and Henry, R and Hsing, YC and Kurata, N and de Oliveira, AC and Panaud, O and Jackson, SA and Machado, CA and Sanderson, MJ and Long, M and Ware, D and Wing, RA}, title = {Genomes of 13 domesticated and wild rice relatives highlight genetic conservation, turnover and innovation across the genus Oryza.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {285-296}, doi = {10.1038/s41588-018-0040-0}, pmid = {29358651}, issn = {1546-1718}, abstract = {The genus Oryza is a model system for the study of molecular evolution over time scales ranging from a few thousand to 15 million years. Using 13 reference genomes spanning the Oryza species tree, we show that despite few large-scale chromosomal rearrangements rapid species diversification is mirrored by lineage-specific emergence and turnover of many novel elements, including transposons, and potential new coding and noncoding genes. Our study resolves controversial areas of the Oryza phylogeny, showing a complex history of introgression among different chromosomes in the young 'AA' subclade containing the two domesticated species. This study highlights the prevalence of functionally coupled disease resistance genes and identifies many new haplotypes of potential use for future crop protection. Finally, this study marks a milestone in modern rice research with the release of a complete long-read assembly of IR 8 'Miracle Rice', which relieved famine and drove the Green Revolution in Asia 50 years ago.}, } @article {pmid29358650, year = {2018}, author = {Mayran, A and Khetchoumian, K and Hariri, F and Pastinen, T and Gauthier, Y and Balsalobre, A and Drouin, J}, title = {Pioneer factor Pax7 deploys a stable enhancer repertoire for specification of cell fate.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {259-269}, doi = {10.1038/s41588-017-0035-2}, pmid = {29358650}, issn = {1546-1718}, abstract = {Pioneer transcription factors establish new cell-fate competence by triggering chromatin remodeling. However, many features of pioneer action, such as their kinetics and stability, remain poorly defined. Here, we show that Pax7, by opening a unique repertoire of enhancers, is necessary and sufficient for specification of one pituitary lineage. Pax7 binds its targeted enhancers rapidly, but chromatin remodeling and gene activation are slower. Enhancers opened by Pax7 show a loss of DNA methylation and acquire stable epigenetic memory, as evidenced by binding of nonpioneer factors after Pax7 withdrawal. This work shows that transient Pax7 expression is sufficient for stable specification of cell identity.}, } @article {pmid29358649, year = {2018}, author = {Coll, F and Phelan, J and Hill-Cawthorne, GA and Nair, MB and Mallard, K and Ali, S and Abdallah, AM and Alghamdi, S and Alsomali, M and Ahmed, AO and Portelli, S and Oppong, Y and Alves, A and Bessa, TB and Campino, S and Caws, M and Chatterjee, A and Crampin, AC and Dheda, K and Furnham, N and Glynn, JR and Grandjean, L and Minh Ha, D and Hasan, R and Hasan, Z and Hibberd, ML and Joloba, M and Jones-López, EC and Matsumoto, T and Miranda, A and Moore, DJ and Mocillo, N and Panaiotov, S and Parkhill, J and Penha, C and Perdigão, J and Portugal, I and Rchiad, Z and Robledo, J and Sheen, P and Shesha, NT and Sirgel, FA and Sola, C and Oliveira Sousa, E and Streicher, EM and Helden, PV and Viveiros, M and Warren, RM and McNerney, R and Pain, A and Clark, TG}, title = {Genome-wide analysis of multi- and extensively drug-resistant Mycobacterium tuberculosis.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {307-316}, doi = {10.1038/s41588-017-0029-0}, pmid = {29358649}, issn = {1546-1718}, support = {098610//Wellcome Trust/United Kingdom ; MR/K020420/1//Medical Research Council/United Kingdom ; }, abstract = {To characterize the genetic determinants of resistance to antituberculosis drugs, we performed a genome-wide association study (GWAS) of 6,465 Mycobacterium tuberculosis clinical isolates from more than 30 countries. A GWAS approach within a mixed-regression framework was followed by a phylogenetics-based test for independent mutations. In addition to mutations in established and recently described resistance-associated genes, novel mutations were discovered for resistance to cycloserine, ethionamide and para-aminosalicylic acid. The capacity to detect mutations associated with resistance to ethionamide, pyrazinamide, capreomycin, cycloserine and para-aminosalicylic acid was enhanced by inclusion of insertions and deletions. Odds ratios for mutations within candidate genes were found to reflect levels of resistance. New epistatic relationships between candidate drug-resistance-associated genes were identified. Findings also suggest the involvement of efflux pumps (drrA and Rv2688c) in the emergence of resistance. This study will inform the design of new diagnostic tests and expedite the investigation of resistance and compensatory epistatic mechanisms.}, } @article {pmid29358610, year = {2018}, author = {Pedersen, CT and Albrechtsen, A and Etter, PD and Johnson, EA and Orlando, L and Chikhi, L and Siegismund, HR and Heller, R}, title = {A southern African origin and cryptic structure in the highly mobile plains zebra.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {491-498}, doi = {10.1038/s41559-017-0453-7}, pmid = {29358610}, issn = {2397-334X}, abstract = {The plains zebra (Equus quagga) is an ecologically important species of the African savannah. It is also one of the most numerous and widely distributed ungulates, and six subspecies have been described based on morphological variation. However, the within-species evolutionary processes have been difficult to resolve due to its high mobility and a lack of consensus regarding the population structure. We obtained genome-wide DNA polymorphism data from more than 167,000 loci for 59 plains zebras from across the species range, encompassing all recognized extant subspecies, as well as three mountain zebras (Equus zebra) and three Grevy's zebras (Equus grevyi). Surprisingly, the population genetic structure does not mirror the morphology-based subspecies delineation, underlining the dangers of basing management units exclusively on morphological variation. We use demographic modelling to provide insights into the past phylogeography of the species. The results identify a southern African location as the most likely source region from which all extant populations expanded around 370,000 years ago. We show evidence for inclusion of the extinct and phenotypically divergent quagga (Equus quagga quagga) in the plains zebra variation and reveal that it was less divergent from the other subspecies than the northernmost (Ugandan) extant population.}, } @article {pmid29358609, year = {2018}, author = {Williamson, P}, title = {Biodiversity risks of climate control.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {416-417}, doi = {10.1038/s41559-017-0460-8}, pmid = {29358609}, issn = {2397-334X}, } @article {pmid29358608, year = {2018}, author = {Trisos, CH and Amatulli, G and Gurevitch, J and Robock, A and Xia, L and Zambri, B}, title = {Potentially dangerous consequences for biodiversity of solar geoengineering implementation and termination.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {475-482}, doi = {10.1038/s41559-017-0431-0}, pmid = {29358608}, issn = {2397-334X}, abstract = {Solar geoengineering is receiving increased policy attention as a potential tool to offset climate warming. While climate responses to geoengineering have been studied in detail, the potential biodiversity consequences are largely unknown. To avoid extinction, species must either adapt or move to track shifting climates. Here, we assess the effects of the rapid implementation, continuation and sudden termination of geoengineering on climate velocities-the speeds and directions that species would need to move to track changes in climate. Compared to a moderate climate change scenario (RCP4.5), rapid geoengineering implementation reduces temperature velocities towards zero in terrestrial biodiversity hotspots. In contrast, sudden termination increases both ocean and land temperature velocities to unprecedented speeds (global medians >10 km yr-1) that are more than double the temperature velocities for recent and future climate change in global biodiversity hotspots. Furthermore, as climate velocities more than double in speed, rapid climate fragmentation occurs in biomes such as temperate grasslands and forests where temperature and precipitation velocity vectors diverge spatially by >90°. Rapid geoengineering termination would significantly increase the threats to biodiversity from climate change.}, } @article {pmid29358607, year = {2018}, author = {Yao, Q and Li, Z and Song, Y and Wright, SJ and Guo, X and Tringe, SG and Tfaily, MM and Paša-Tolić, L and Hazen, TC and Turner, BL and Mayes, MA and Pan, C}, title = {Community proteogenomics reveals the systemic impact of phosphorus availability on microbial functions in tropical soil.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {499-509}, doi = {10.1038/s41559-017-0463-5}, pmid = {29358607}, issn = {2397-334X}, abstract = {Phosphorus is a scarce nutrient in many tropical ecosystems, yet how soil microbial communities cope with growth-limiting phosphorus deficiency at the gene and protein levels remains unknown. Here, we report a metagenomic and metaproteomic comparison of microbial communities in phosphorus-deficient and phosphorus-rich soils in a 17-year fertilization experiment in a tropical forest. The large-scale proteogenomics analyses provided extensive coverage of many microbial functions and taxa in the complex soil communities. A greater than fourfold increase in the gene abundance of 3-phytase was the strongest response of soil communities to phosphorus deficiency. Phytase catalyses the release of phosphate from phytate, the most recalcitrant phosphorus-containing compound in soil organic matter. Genes and proteins for the degradation of phosphorus-containing nucleic acids and phospholipids, as well as the decomposition of labile carbon and nitrogen, were also enhanced in the phosphorus-deficient soils. In contrast, microbial communities in the phosphorus-rich soils showed increased gene abundances for the degradation of recalcitrant aromatic compounds, transformation of nitrogenous compounds and assimilation of sulfur. Overall, these results demonstrate the adaptive allocation of genes and proteins in soil microbial communities in response to shifting nutrient constraints.}, } @article {pmid29358606, year = {2018}, author = {St Clair, JJH and Klump, BC and Sugasawa, S and Higgott, CG and Colegrave, N and Rutz, C}, title = {Hook innovation boosts foraging efficiency in tool-using crows.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {441-444}, doi = {10.1038/s41559-017-0429-7}, pmid = {29358606}, issn = {2397-334X}, abstract = {The New Caledonian crow is the only non-human animal known to craft hooked tools in the wild, but the ecological benefit of these relatively complex tools remains unknown. Here, we show that crows acquire food several times faster when using hooked rather than non-hooked tools, regardless of tool material, prey type and extraction context. This implies that small changes to tool shape can strongly affect energy-intake rates, highlighting a powerful driver for technological advancement.}, } @article {pmid29358605, year = {2018}, author = {Bobrovskiy, I and Hope, JM and Krasnova, A and Ivantsov, A and Brocks, JJ}, title = {Molecular fossils from organically preserved Ediacara biota reveal cyanobacterial origin for Beltanelliformis.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {437-440}, doi = {10.1038/s41559-017-0438-6}, pmid = {29358605}, issn = {2397-334X}, abstract = {The Ediacara biota (~575-541 million years ago) mark the emergence of large, complex organisms in the palaeontological record, preluding the radiation of modern animal phyla. However, their phylogenetic relationships, even at the domain level, remain controversial. We report the discovery of molecular fossils from organically preserved specimens of Beltanelliformis, demonstrating that they represent large spherical colonies of cyanobacteria. The conservation of molecular remains in organically preserved Ediacaran organisms opens a new path for unravelling the natures of the Ediacara biota.}, } @article {pmid29358410, year = {2018}, author = {Metzler, H and Müller, M and Sierra, CA}, title = {Transit-time and age distributions for nonlinear time-dependent compartmental systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1150-1155}, pmid = {29358410}, issn = {1091-6490}, abstract = {Many processes in nature are modeled using compartmental systems (reservoir/pool/box systems). Usually, they are expressed as a set of first-order differential equations describing the transfer of matter across a network of compartments. The concepts of age of matter in compartments and the time required for particles to transit the system are important diagnostics of these models with applications to a wide range of scientific questions. Until now, explicit formulas for transit-time and age distributions of nonlinear time-dependent compartmental systems were not available. We compute densities for these types of systems under the assumption of well-mixed compartments. Assuming that a solution of the nonlinear system is available at least numerically, we show how to construct a linear time-dependent system with the same solution trajectory. We demonstrate how to exploit this solution to compute transit-time and age distributions in dependence on given start values and initial age distributions. Furthermore, we derive equations for the time evolution of quantiles and moments of the age distributions. Our results generalize available density formulas for the linear time-independent case and mean-age formulas for the linear time-dependent case. As an example, we apply our formulas to a nonlinear and a linear version of a simple global carbon cycle model driven by a time-dependent input signal which represents fossil fuel additions. We derive time-dependent age distributions for all compartments and calculate the time it takes to remove fossil carbon in a business-as-usual scenario.}, } @article {pmid29358409, year = {2018}, author = {Quax, TEF and Altegoer, F and Rossi, F and Li, Z and Rodriguez-Franco, M and Kraus, F and Bange, G and Albers, SV}, title = {Structure and function of the archaeal response regulator CheY.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1259-E1268}, pmid = {29358409}, issn = {1091-6490}, support = {311523//European Research Council/International ; }, mesh = {Amino Acid Sequence ; Archaea/*physiology ; Archaeal Proteins/*chemistry/*metabolism ; Chemotaxis/*physiology ; Crystallography, X-Ray ; Models, Molecular ; Protein Conformation ; Sequence Homology ; }, abstract = {Motility is a central feature of many microorganisms and provides an efficient strategy to respond to environmental changes. Bacteria and archaea have developed fundamentally different rotary motors enabling their motility, termed flagellum and archaellum, respectively. Bacterial motility along chemical gradients, called chemotaxis, critically relies on the response regulator CheY, which, when phosphorylated, inverses the rotational direction of the flagellum via a switch complex at the base of the motor. The structural difference between archaellum and flagellum and the presence of functional CheY in archaea raises the question of how the CheY protein changed to allow communication with the archaeal motility machinery. Here we show that archaeal CheY shares the overall structure and mechanism of magnesium-dependent phosphorylation with its bacterial counterpart. However, bacterial and archaeal CheY differ in the electrostatic potential of the helix α4. The helix α4 is important in bacteria for interaction with the flagellar switch complex, a structure that is absent in archaea. We demonstrated that phosphorylation-dependent activation, and conserved residues in the archaeal CheY helix α4, are important for interaction with the archaeal-specific adaptor protein CheF. This forms a bridge between the chemotaxis system and the archaeal motility machinery. Conclusively, archaeal CheY proteins conserved the central mechanistic features between bacteria and archaea, but differ in the helix α4 to allow binding to an archaellum-specific interaction partner.}, } @article {pmid29358408, year = {2018}, author = {Mahgoub, M and Yasunaga, JI and Iwami, S and Nakaoka, S and Koizumi, Y and Shimura, K and Matsuoka, M}, title = {Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1269-E1278}, pmid = {29358408}, issn = {1091-6490}, mesh = {*Gene Expression Regulation, Viral ; Gene Products, tax/genetics/*metabolism ; HTLV-I Infections/genetics/metabolism/*virology ; Human T-lymphotropic virus 1/*pathogenicity ; Humans ; Leukemia-Lymphoma, Adult T-Cell/genetics/metabolism/*virology ; Single-Cell Analysis ; T-Lymphocytes/*virology ; Virus Activation ; *Virus Replication ; }, abstract = {Viruses causing chronic infection artfully manipulate infected cells to enable viral persistence in vivo under the pressure of immunity. Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infection mainly in CD4+ T cells in vivo and induces leukemia in this subset. HTLV-1-encoded Tax is a critical transactivator of viral replication and a potent oncoprotein, but its significance in pathogenesis remains obscure due to its very low level of expression in vivo. Here, we show that Tax is expressed in a minor fraction of leukemic cells at any given time, and importantly, its expression spontaneously switches between on and off states. Live cell imaging revealed that the average duration of one episode of Tax expression is ∼19 hours. Knockdown of Tax rapidly induced apoptosis in most cells, indicating that Tax is critical for maintaining the population, even if its short-term expression is limited to a small subpopulation. Single-cell analysis and computational simulation suggest that transient Tax expression triggers antiapoptotic machinery, and this effect continues even after Tax expression is diminished; this activation of the antiapoptotic machinery is the critical event for maintaining the population. In addition, Tax is induced by various cytotoxic stresses and also promotes HTLV-1 replication. Thus, it seems that Tax protects infected cells from apoptosis and increases the chance of viral transmission at a critical moment. Keeping the expression of Tax minimal but inducible on demand is, therefore, a fundamental strategy of HTLV-1 to promote persistent infection and leukemogenesis.}, } @article {pmid29358407, year = {2018}, author = {Mao, S and Shah, AS and Moninger, TO and Ostedgaard, LS and Lu, L and Tang, XX and Thornell, IM and Reznikov, LR and Ernst, SE and Karp, PH and Tan, P and Keshavjee, S and Abou Alaiwa, MH and Welsh, MJ}, title = {Motile cilia of human airway epithelia contain hedgehog signaling components that mediate noncanonical hedgehog signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1370-1375}, pmid = {29358407}, issn = {1091-6490}, support = {P01 HL051670/HL/NHLBI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; F32 HL009184/HL/NHLBI NIH HHS/United States ; P30 DK054759/DK/NIDDK NIH HHS/United States ; K99 HL119560/HL/NHLBI NIH HHS/United States ; }, mesh = {Bronchi/*cytology ; Cells, Cultured ; Cilia/metabolism/physiology ; Cyclic AMP/metabolism ; Epithelial Cells/cytology/*metabolism ; Hedgehog Proteins/*metabolism ; Humans ; Nuclear Proteins/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; Signal Transduction ; Smoothened Receptor/genetics/metabolism ; Trachea/*cytology ; Zinc Finger Protein Gli2/genetics/metabolism ; }, abstract = {Differentiated airway epithelia produce sonic hedgehog (SHH), which is found in the thin layer of liquid covering the airway surface. Although previous studies showed that vertebrate HH signaling requires primary cilia, as airway epithelia mature, the cells lose primary cilia and produce hundreds of motile cilia. Thus, whether airway epithelia have apical receptors for SHH has remained unknown. We discovered that motile cilia on airway epithelial cells have HH signaling proteins, including patched and smoothened. These cilia also have proteins affecting cAMP-dependent signaling, including Gαi and adenylyl cyclase 5/6. Apical SHH decreases intracellular levels of cAMP, which reduces ciliary beat frequency and pH in airway surface liquid. These results suggest that apical SHH may mediate noncanonical HH signaling through motile cilia to dampen respiratory defenses at the contact point between the environment and the lung, perhaps counterbalancing processes that stimulate airway defenses.}, } @article {pmid29358406, year = {2018}, author = {Bennett, M and Cantini, M and Reboud, J and Cooper, JM and Roca-Cusachs, P and Salmeron-Sanchez, M}, title = {Molecular clutch drives cell response to surface viscosity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1192-1197}, pmid = {29358406}, issn = {1091-6490}, mesh = {Actins/metabolism ; Adaptor Proteins, Signal Transducing/*metabolism ; Animals ; Cell Line ; Cell Shape ; Extracellular Matrix/chemistry/metabolism ; Fibronectins/chemistry ; Focal Adhesion Kinase 1/*metabolism ; Focal Adhesions ; Lipid Bilayers/*chemistry/metabolism ; Mice ; Microscopy, Atomic Force ; Myoblasts/*cytology/metabolism ; Oligopeptides/chemistry/metabolism ; Phosphatidylcholines/chemistry ; Phosphoproteins/*metabolism ; Surface Properties ; Viscosity ; }, abstract = {Cell response to matrix rigidity has been explained by the mechanical properties of the actin-talin-integrin-fibronectin clutch. Here the molecular clutch model is extended to account for cell interactions with purely viscous surfaces (i.e., without an elastic component). Supported lipid bilayers present an idealized and controllable system through which to study this concept. Using lipids of different diffusion coefficients, the mobility (i.e., surface viscosity) of the presented ligands (in this case RGD) was altered by an order of magnitude. Cell size and cytoskeletal organization were proportional to viscosity. Furthermore, there was a higher number of focal adhesions and a higher phosphorylation of FAK on less-mobile (more-viscous) surfaces. Actin retrograde flow, an indicator of the force exerted on surfaces, was also seen to be faster on more mobile surfaces. This has consequential effects on downstream molecules; the mechanosensitive YAP protein localized to the nucleus more on less-mobile (more-viscous) surfaces and differentiation of myoblast cells was enhanced on higher viscosity. This behavior was explained within the framework of the molecular clutch model, with lower viscosity leading to a low force loading rate, preventing the exposure of mechanosensitive proteins, and with a higher viscosity causing a higher force loading rate exposing these sites, activating downstream pathways. Consequently, the understanding of how viscosity (regardless of matrix stiffness) influences cell response adds a further tool to engineer materials that control cell behavior.}, } @article {pmid29358405, year = {2018}, author = {Fitzpatrick, CR and Copeland, J and Wang, PW and Guttman, DS and Kotanen, PM and Johnson, MTJ}, title = {Assembly and ecological function of the root microbiome across angiosperm plant species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1157-E1165}, pmid = {29358405}, issn = {1091-6490}, mesh = {Bacteria/*genetics ; Droughts ; *Ecology ; Magnoliopsida/*microbiology ; *Microbiota ; Phylogeny ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S ; *Rhizosphere ; Soil Microbiology ; Symbiosis/*genetics ; }, abstract = {Across plants and animals, host-associated microbial communities play fundamental roles in host nutrition, development, and immunity. The factors that shape host-microbiome interactions are poorly understood, yet essential for understanding the evolution and ecology of these symbioses. Plant roots assemble two distinct microbial compartments from surrounding soil: the rhizosphere (microbes surrounding roots) and the endosphere (microbes within roots). Root-associated microbes were key for the evolution of land plants and underlie fundamental ecosystem processes. However, it is largely unknown how plant evolution has shaped root microbial communities, and in turn, how these microbes affect plant ecology, such as the ability to mitigate biotic and abiotic stressors. Here we show that variation among 30 angiosperm species, which have diverged for up to 140 million years, affects root bacterial diversity and composition. Greater similarity in root microbiomes between hosts leads to negative effects on plant performance through soil feedback, with specific microbial taxa in the endosphere and rhizosphere potentially affecting competitive interactions among plant species. Drought also shifts the composition of root microbiomes, most notably by increasing the relative abundance of the Actinobacteria. However, this drought response varies across host plant species, and host-specific changes in the relative abundance of endosphere Streptomyces are associated with host drought tolerance. Our results emphasize the causes of variation in root microbiomes and their ecological importance for plant performance in response to biotic and abiotic stressors.}, } @article {pmid29358404, year = {2018}, author = {Siracusa, F and McGrath, MA and Maschmeyer, P and Bardua, M and Lehmann, K and Heinz, G and Durek, P and Heinrich, FF and Mashreghi, MF and Chang, HD and Tokoyoda, K and Radbruch, A}, title = {Nonfollicular reactivation of bone marrow resident memory CD4 T cells in immune clusters of the bone marrow.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1334-1339}, pmid = {29358404}, issn = {1091-6490}, support = {268987//European Research Council/International ; }, mesh = {Animals ; B-Lymphocytes/immunology ; Bone Marrow/drug effects/*immunology ; CD4-Positive T-Lymphocytes/cytology/*immunology ; Cell Movement ; Cell Proliferation ; Fingolimod Hydrochloride/immunology/pharmacology ; Gene Expression Regulation/immunology ; Immunization, Secondary ; *Immunologic Memory ; Immunosuppressive Agents/pharmacology ; Lymphocyte Activation ; Male ; Mice, Inbred C57BL ; Receptors, CXCR5/genetics/immunology ; Spleen/cytology/immunology ; }, abstract = {The bone marrow maintains memory CD4 T cells, which provide memory to systemic antigens. Here we demonstrate that memory CD4 T cells are reactivated by antigen in the bone marrow. In a secondary immune response, antigen-specific T cells of the bone marrow mobilize and aggregate in immune clusters together with MHC class II-expressing cells, mostly B lymphocytes. They proliferate vigorously and express effector cytokines, but they do not develop into follicular T-helper cells. Neither do the B lymphocytes develop into germinal center B cells in the bone marrow. Within 10 days, the immune clusters disappear again. Within 30 days, the expanded antigen-specific memory CD4 T cells return to memory niches and are maintained again individually as resting cells. Thus, in secondary immune responses in the bone marrow T-cell memory is amplified, while in germinal center reactions of secondary lymphoid organs humoral memory is adapted by affinity maturation.}, } @article {pmid29358403, year = {2018}, author = {Lerdkrai, C and Asavapanumas, N and Brawek, B and Kovalchuk, Y and Mojtahedi, N and Olmedillas Del Moral, M and Garaschuk, O}, title = {Intracellular Ca2+ stores control in vivo neuronal hyperactivity in a mouse model of Alzheimer's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1279-E1288}, pmid = {29358403}, issn = {1091-6490}, mesh = {Aging ; Alzheimer Disease/metabolism/*pathology ; Animals ; Calcium/*metabolism ; Calcium Channels/*metabolism ; *Disease Models, Animal ; Humans ; Inflammation/metabolism/*pathology ; Mice ; Neurons/metabolism/*pathology ; Plaque, Amyloid/metabolism/pathology ; Presenilin-1/*physiology ; Presynaptic Terminals/metabolism/pathology ; Signal Transduction ; }, abstract = {Neuronal hyperactivity is the emerging functional hallmark of Alzheimer's disease (AD) in both humans and different mouse models, mediating an impairment of memory and cognition. The mechanisms underlying neuronal hyperactivity remain, however, elusive. In vivo Ca2+ imaging of somatic, dendritic, and axonal activity patterns of cortical neurons revealed that both healthy aging and AD-related mutations augment neuronal hyperactivity. The AD-related enhancement occurred even without amyloid deposition and neuroinflammation, mainly due to presenilin-mediated dysfunction of intracellular Ca2+ stores in presynaptic boutons, likely causing more frequent activation of synaptic NMDA receptors. In mutant but not wild-type mice, store emptying reduced both the frequency and amplitude of presynaptic Ca2+ transients and, most importantly, normalized neuronal network activity. Postsynaptically, the store dysfunction was minor and largely restricted to hyperactive cells. These findings identify presynaptic Ca2+ stores as a key element controlling AD-related neuronal hyperactivity and as a target for disease-modifying treatments.}, } @article {pmid29358402, year = {2018}, author = {}, title = {Correction for Droog et al., Estrogen receptor α wields treatment-specific enhancers between morphologically similar endometrial tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1075}, doi = {10.1073/pnas.1800091115}, pmid = {29358402}, issn = {1091-6490}, } @article {pmid29358401, year = {2018}, author = {Horani, A and Ustione, A and Huang, T and Firth, AL and Pan, J and Gunsten, SP and Haspel, JA and Piston, DW and Brody, SL}, title = {Establishment of the early cilia preassembly protein complex during motile ciliogenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1221-E1228}, pmid = {29358401}, issn = {1091-6490}, support = {R01 HL128370/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Antigens, Surface/genetics/*metabolism ; Cells, Cultured ; Cilia/*physiology ; GTP-Binding Proteins/genetics/*metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/*physiology ; Mice ; Microtubule-Associated Proteins/genetics/*metabolism ; Mutation ; Phenotype ; Proteins/genetics/*metabolism ; Respiratory Mucosa/cytology/*physiology ; }, abstract = {Motile cilia are characterized by dynein motor units, which preassemble in the cytoplasm before trafficking into the cilia. Proteins required for dynein preassembly were discovered by finding human mutations that result in absent ciliary motors, but little is known about their expression, function, or interactions. By monitoring ciliogenesis in primary airway epithelial cells and MCIDAS-regulated induced pluripotent stem cells, we uncovered two phases of expression of preassembly proteins. An early phase, composed of HEATR2, SPAG1, and DNAAF2, preceded other preassembly proteins and was independent of MCIDAS regulation. The early preassembly proteins colocalized within perinuclear foci that also contained dynein arm proteins. These proteins also interacted based on immunoprecipitation and Förster resonance energy transfer (FRET) studies. FRET analysis of HEAT domain deletions and human mutations showed that HEATR2 interacted with itself and SPAG1 at multiple HEAT domains, while DNAAF2 interacted with SPAG1. Human mutations in HEATR2 did not affect this interaction, but triggered the formation of p62/Sequestosome-1-positive aggregates containing the early preassembly proteins, suggesting that degradation of an early preassembly complex is responsible for disease and pointing to key regions required for HEATR2 scaffold stability. We speculate that HEATR2 is an early scaffold for the initiation of dynein complex assembly in motile cilia.}, } @article {pmid29358400, year = {2018}, author = {Li, S and Guo, J and Reva, A and Huang, F and Xiong, B and Liu, Y and Deng, Z and Leadlay, PF and Sun, Y}, title = {Methyltransferases of gentamicin biosynthesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1340-1345}, pmid = {29358400}, issn = {1091-6490}, support = {G1001687//Medical Research Council/United Kingdom ; MR/M019020/1//Medical Research Council/United Kingdom ; 1343325//Medical Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/genetics/metabolism ; Gene Deletion ; Gentamicins/*biosynthesis/metabolism ; Methylation ; Methyltransferases/genetics/*metabolism ; Micromonospora/*enzymology/*genetics/metabolism ; Multigene Family ; Mutation ; Spectrometry, Mass, Electrospray Ionization ; Substrate Specificity ; }, abstract = {Gentamicin C complex from Micromonospora echinospora remains a globally important antibiotic, and there is revived interest in the semisynthesis of analogs that might show improved therapeutic properties. The complex consists of five components differing in their methylation pattern at one or more sites in the molecule. We show here, using specific gene deletion and chemical complementation, that the gentamicin pathway up to the branch point is defined by the selectivity of the methyltransferases GenN, GenD1, and GenK. Unexpectedly, they comprise a methylation network in which early intermediates are ectopically modified. Using whole-genome sequence, we have also discovered the terminal 6'-N-methyltransfer required to produce gentamicin C2b from C1a or gentamicin C1 from C2, an example of an essential biosynthetic enzyme being located not in the biosynthetic gene cluster but far removed on the chromosome. These findings fully account for the methylation pattern in gentamicins and open the way to production of individual gentamicins by fermentation, as starting materials for semisynthesis.}, } @article {pmid29358399, year = {2018}, author = {Bennett, RE and Robbins, AB and Hu, M and Cao, X and Betensky, RA and Clark, T and Das, S and Hyman, BT}, title = {Tau induces blood vessel abnormalities and angiogenesis-related gene expression in P301L transgenic mice and human Alzheimer's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1289-E1298}, pmid = {29358399}, issn = {1091-6490}, support = {U01 AG046152/AG/NIA NIH HHS/United States ; T32 AG000222/AG/NIA NIH HHS/United States ; U01 AG032984/AG/NIA NIH HHS/United States ; R01 AG030146/AG/NIA NIH HHS/United States ; R01 AG017917/AG/NIA NIH HHS/United States ; P50 AG005134/AG/NIA NIH HHS/United States ; P30 AG010161/AG/NIA NIH HHS/United States ; R01 AG026249/AG/NIA NIH HHS/United States ; R01 AG036836/AG/NIA NIH HHS/United States ; R01 AG015819/AG/NIA NIH HHS/United States ; }, mesh = {Aging ; Alzheimer Disease/genetics/metabolism/*pathology ; Amyloid beta-Peptides/*metabolism ; Angiogenesis Inducing Agents/*metabolism ; Animals ; Brain/*blood supply/metabolism/pathology ; Cells, Cultured ; Cerebrovascular Circulation/*physiology ; Humans ; Mice ; Mice, Transgenic ; Neurons/metabolism/*pathology ; tau Proteins/genetics/*metabolism ; }, abstract = {Mixed pathology, with both Alzheimer's disease and vascular abnormalities, is the most common cause of clinical dementia in the elderly. While usually thought to be concurrent diseases, the fact that changes in cerebral blood flow are a prominent early and persistent alteration in Alzheimer's disease raises the possibility that vascular alterations and Alzheimer pathology are more directly linked. Here, we report that aged tau-overexpressing mice develop changes to blood vessels including abnormal, spiraling morphologies; reduced blood vessel diameters; and increased overall blood vessel density in cortex. Blood flow in these vessels was altered, with periods of obstructed flow rarely observed in normal capillaries. These changes were accompanied by cortical atrophy as well as increased expression of angiogenesis-related genes such as Vegfa, Serpine1, and Plau in CD31-positive endothelial cells. Interestingly, mice overexpressing nonmutant forms of tau in the absence of frank neurodegeneration also demonstrated similar changes. Furthermore, many of the genes we observe in mice are also altered in human RNA datasets from Alzheimer patients, particularly in brain regions classically associated with tau pathology such as the temporal lobe and limbic system regions. Together these data indicate that tau pathological changes in neurons can impact brain endothelial cell biology, altering the integrity of the brain's microvasculature.}, } @article {pmid29358398, year = {2018}, author = {Son, M and Wickner, RB}, title = {Nonsense-mediated mRNA decay factors cure most [PSI+] prion variants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1184-E1193}, pmid = {29358398}, issn = {1091-6490}, mesh = {Adaptor Proteins, Signal Transducing/genetics/metabolism ; Codon, Nonsense ; Gene Expression Regulation, Fungal ; Nonsense Mediated mRNA Decay/*genetics ; Peptide Termination Factors/genetics/metabolism ; Prions/genetics/*metabolism ; Protein Biosynthesis ; RNA Helicases/genetics/metabolism ; RNA, Messenger/genetics/*metabolism ; RNA-Binding Proteins/genetics/metabolism ; Saccharomyces cerevisiae/genetics/growth & development/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; Transcription, Genetic ; }, abstract = {The yeast prion [PSI+] is a self-propagating amyloid of Sup35p with a folded in-register parallel β-sheet architecture. In a genetic screen for antiprion genes, using the yeast knockout collection, UPF1/NAM7 and UPF3, encoding nonsense-mediated mRNA decay (NMD) factors, were frequently detected. Almost all [PSI+] variants arising in the absence of Upf proteins were eliminated by restored normal levels of these proteins, and [PSI+] arises more frequently in upf mutants. Upf1p, complexed with Upf2p and Upf3p, is a multifunctional protein with helicase, ATP-binding, and RNA-binding activities promoting efficient translation termination and degradation of mRNAs with premature nonsense codons. We find that the curing ability of Upf proteins is uncorrelated with these previously reported functions but does depend on their interaction with Sup35p and formation of the Upf1p-Upf2p-Upf3p complex (i.e., the Upf complex). Indeed, Sup35p amyloid formation in vitro is inhibited by substoichiometric Upf1p. Inhibition of [PSI+] prion generation and propagation by Upf proteins may be due to the monomeric Upf proteins and the Upf complex competing with Sup35p amyloid fibers for available Sup35p monomers. Alternatively, the association of the Upf complex with amyloid filaments may block the addition of new monomers. Our results suggest that maintenance of normal protein-protein interactions prevents prion formation and can even reverse the process.}, } @article {pmid29358397, year = {2018}, author = {Kapnick, SB and Yang, X and Vecchi, GA and Delworth, TL and Gudgel, R and Malyshev, S and Milly, PCD and Shevliakova, E and Underwood, S and Margulis, SA}, title = {Potential for western US seasonal snowpack prediction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1180-1185}, pmid = {29358397}, issn = {1091-6490}, abstract = {Western US snowpack-snow that accumulates on the ground in the mountains-plays a critical role in regional hydroclimate and water supply, with 80% of snowmelt runoff being used for agriculture. While climate projections provide estimates of snowpack loss by the end of the century and weather forecasts provide predictions of weather conditions out to 2 weeks, less progress has been made for snow predictions at seasonal timescales (months to 2 years), crucial for regional agricultural decisions (e.g., plant choice and quantity). Seasonal predictions with climate models first took the form of El Niño predictions 3 decades ago, with hydroclimate predictions emerging more recently. While the field has been focused on single-season predictions (3 months or less), we are now poised to advance our predictions beyond this timeframe. Utilizing observations, climate indices, and a suite of global climate models, we demonstrate the feasibility of seasonal snowpack predictions and quantify the limits of predictive skill 8 months in advance. This physically based dynamic system outperforms observation-based statistical predictions made on July 1 for March snowpack everywhere except the southern Sierra Nevada, a region where prediction skill is nonexistent for every predictor presently tested. Additionally, in the absence of externally forced negative trends in snowpack, narrow maritime mountain ranges with high hydroclimate variability pose a challenge for seasonal prediction in our present system; natural snowpack variability may inherently be unpredictable at this timescale. This work highlights present prediction system successes and gives cause for optimism for developing seasonal predictions for societal needs.}, } @article {pmid29358396, year = {2018}, author = {Luo, L and Li, B and Wang, S and Wu, F and Wang, X and Liang, P and Ombati, R and Chen, J and Lu, X and Cui, J and Lu, Q and Zhang, L and Zhou, M and Tian, C and Yang, S and Lai, R}, title = {Centipedes subdue giant prey by blocking KCNQ channels.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1646-1651}, pmid = {29358396}, issn = {1091-6490}, mesh = {Animals ; Anticonvulsants/pharmacology ; Arthropod Venoms/*toxicity ; Arthropods/*physiology ; Carbamates/pharmacology ; KCNQ Potassium Channels/*antagonists & inhibitors ; Mice ; Nervous System Diseases/*chemically induced/drug therapy/metabolism ; Phenylenediamines/pharmacology ; Predatory Behavior/*drug effects ; Respiratory System Abnormalities/*chemically induced/drug therapy/metabolism ; }, abstract = {Centipedes can subdue giant prey by using venom, which is metabolically expensive to synthesize and thus used frugally through efficiently disrupting essential physiological systems. Here, we show that a centipede (Scolopendra subspinipes mutilans, ∼3 g) can subdue a mouse (∼45 g) within 30 seconds. We found that this observation is largely due to a peptide toxin in the venom, SsTx, and further established that SsTx blocks KCNQ potassium channels to exert the lethal toxicity. We also demonstrated that a KCNQ opener, retigabine, neutralizes the toxicity of a centipede's venom. The study indicates that centipedes' venom has evolved to simultaneously disrupt cardiovascular, respiratory, muscular, and nervous systems by targeting the broadly distributed KCNQ channels, thus providing a therapeutic strategy for centipede envenomation.}, } @article {pmid29358395, year = {2018}, author = {Yamashita, S and Kishino, T and Takahashi, T and Shimazu, T and Charvat, H and Kakugawa, Y and Nakajima, T and Lee, YC and Iida, N and Maeda, M and Hattori, N and Takeshima, H and Nagano, R and Oda, I and Tsugane, S and Wu, MS and Ushijima, T}, title = {Genetic and epigenetic alterations in normal tissues have differential impacts on cancer risk among tissues.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1328-1333}, pmid = {29358395}, issn = {1091-6490}, mesh = {Biomarkers, Tumor/genetics ; Carcinoma, Squamous Cell/*genetics ; DNA Methylation ; *Epigenesis, Genetic ; Esophageal Neoplasms/*genetics ; Esophageal Squamous Cell Carcinoma ; Female ; Gastric Mucosa/*physiology ; Genome-Wide Association Study ; Helicobacter Infections/complications ; Humans ; Male ; Mutation Rate ; Point Mutation ; Risk Factors ; Stomach Neoplasms/*genetics ; Transcription Factor AP-2/genetics ; }, abstract = {Genetic and epigenetic alterations are both involved in carcinogenesis, and their low-level accumulation in normal tissues constitutes cancer risk. However, their relative importance has never been examined, as measurement of low-level mutations has been difficult. Here, we measured low-level accumulations of genetic and epigenetic alterations in normal tissues with low, intermediate, and high cancer risk and analyzed their relative effects on cancer risk in the esophagus and stomach. Accumulation of genetic alterations, estimated as a frequency of rare base substitution mutations, significantly increased according to cancer risk in esophageal mucosae, but not in gastric mucosae. The mutation patterns reflected the exposure to lifestyle risk factors. In contrast, the accumulation of epigenetic alterations, measured as DNA methylation levels of marker genes, significantly increased according to cancer risk in both tissues. Patients with cancer (high-risk individuals) were precisely discriminated from healthy individuals with exposure to risk factors (intermediate-risk individuals) by a combination of alterations in the esophagus (odds ratio, 18.2; 95% confidence interval, 3.69-89.9) and by only epigenetic alterations in the stomach (odds ratio, 7.67; 95% confidence interval, 2.52-23.3). The relative importance of epigenetic alterations upon genetic alterations was 1.04 in the esophagus and 2.31 in the stomach. The differential impacts among tissues will be critically important for effective cancer prevention and precision cancer risk diagnosis.}, } @article {pmid29358394, year = {2018}, author = {Scanlon, BR and Zhang, Z and Save, H and Sun, AY and Müller Schmied, H and van Beek, LPH and Wiese, DN and Wada, Y and Long, D and Reedy, RC and Longuevergne, L and Döll, P and Bierkens, MFP}, title = {Global models underestimate large decadal declining and rising water storage trends relative to GRACE satellite data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1080-E1089}, pmid = {29358394}, issn = {1091-6490}, abstract = {Assessing reliability of global models is critical because of increasing reliance on these models to address past and projected future climate and human stresses on global water resources. Here, we evaluate model reliability based on a comprehensive comparison of decadal trends (2002-2014) in land water storage from seven global models (WGHM, PCR-GLOBWB, GLDAS NOAH, MOSAIC, VIC, CLM, and CLSM) to trends from three Gravity Recovery and Climate Experiment (GRACE) satellite solutions in 186 river basins (∼60% of global land area). Medians of modeled basin water storage trends greatly underestimate GRACE-derived large decreasing (≤-0.5 km3/y) and increasing (≥0.5 km3/y) trends. Decreasing trends from GRACE are mostly related to human use (irrigation) and climate variations, whereas increasing trends reflect climate variations. For example, in the Amazon, GRACE estimates a large increasing trend of ∼43 km3/y, whereas most models estimate decreasing trends (-71 to 11 km3/y). Land water storage trends, summed over all basins, are positive for GRACE (∼71-82 km3/y) but negative for models (-450 to -12 km3/y), contributing opposing trends to global mean sea level change. Impacts of climate forcing on decadal land water storage trends exceed those of modeled human intervention by about a factor of 2. The model-GRACE comparison highlights potential areas of future model development, particularly simulated water storage. The inability of models to capture large decadal water storage trends based on GRACE indicates that model projections of climate and human-induced water storage changes may be underestimated.}, } @article {pmid29358393, year = {2018}, author = {Banfi, S and Gusarova, V and Gromada, J and Cohen, JC and Hobbs, HH}, title = {Increased thermogenesis by a noncanonical pathway in ANGPTL3/8-deficient mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1249-E1258}, pmid = {29358393}, issn = {1091-6490}, support = {P01 HL020948/HL/NHLBI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adipose Tissue, Brown/*metabolism ; Adipose Tissue, White/*metabolism ; Angiopoietin-like Proteins/*physiology ; Animals ; Dietary Fats ; Female ; Lipid Metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Oxygen Consumption ; Receptors, Adrenergic, beta-3/metabolism ; Thermogenesis/*physiology ; Triglycerides/*metabolism ; }, abstract = {Dietary triglyceride (TG) is the most efficient energy substrate. It is processed and stored at substantially lower metabolic cost than is protein or carbohydrate. In fed animals, circulating TGs are preferentially routed for storage to white adipose tissue (WAT) by angiopoietin-like proteins 3 (A3) and 8 (A8). Here, we show that mice lacking A3 and A8 (A3-/- A8-/- mice) have decreased fat mass and a striking increase in temperature (+1 °C) in the fed (but not fasted) state, without alterations in food intake or physical activity. Subcutaneous WAT (WAT-SQ) from these animals had morphologic and metabolic changes characteristic of beiging. O2 consumption rates (OCRs) and expression of genes involved in both fatty acid synthesis and fatty acid oxidation were increased in WAT-SQ of A3-/- A8-/- mice, but not in their epididymal or brown adipose tissue (BAT). The hyperthermic response to feeding was blocked by maintaining A3-/- A8-/- mice at thermoneutrality or by treating with a β3-adrenergic receptor (AR) antagonist. To determine if sympathetic stimulation was sufficient to increase body temperature in A3-/- A8-/- mice, WT and A3-/- A8-/- animals were maintained at thermoneutrality and then treated with a β3-AR agonist; treatment induced hyperthermia in A3-/- A8-/- , but not WT, mice. Antibody-mediated inactivation of both circulating A3 and A8 induced hyperthermia in WT mice. Together, these data indicate that A3 and A8 are essential for efficient storage of dietary TG and that disruption of these genes increases feeding-induced thermogenesis and energy utilization.}, } @article {pmid29358392, year = {2018}, author = {Paré, A and Mailhot, B and Lévesque, SA and Juzwik, C and Ignatius Arokia Doss, PM and Lécuyer, MA and Prat, A and Rangachari, M and Fournier, A and Lacroix, S}, title = {IL-1β enables CNS access to CCR2hi monocytes and the generation of pathogenic cells through GM-CSF released by CNS endothelial cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1194-E1203}, pmid = {29358392}, issn = {1091-6490}, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology/metabolism/*pathology ; Central Nervous System/immunology/metabolism/*pathology ; Encephalomyelitis, Autoimmune, Experimental/etiology/metabolism/*pathology ; Endothelial Cells/immunology/metabolism/*pathology ; Granulocyte-Macrophage Colony-Stimulating Factor/metabolism ; Inflammation/etiology/metabolism/pathology ; Interleukin-1beta/*physiology ; Mice ; Mice, Knockout ; Monocytes/immunology/metabolism/*pathology ; Myeloid Cells/immunology/metabolism/pathology ; Neurons/immunology/metabolism/*pathology ; Receptors, CCR2/metabolism ; }, abstract = {Molecular interventions that limit pathogenic CNS inflammation are used to treat autoimmune conditions such as multiple sclerosis (MS). Remarkably, IL-1β-knockout mice are highly resistant to experimental autoimmune encephalomyelitis (EAE), an animal model of MS. Here, we show that interfering with the IL-1β/IL-1R1 axis severely impairs the transmigration of myeloid cells across central nervous system (CNS) endothelial cells (ECs). Notably, we report that IL-1β expression by inflammatory CCR2hi monocytes favors their entry into the spinal cord before EAE onset. Following activation with IL-1β, CNS ECs release GM-CSF, which in turn converts monocytes into antigen-presenting cells (APCs). Accordingly, spinal cord-infiltrated monocyte-derived APCs are associated with dividing CD4+ T cells. Factors released from the interaction between IL-1β-competent myeloid cells and CD4+ T cells are highly toxic to neurons. Together, our results suggest that IL-1β signaling is an entry point for targeting both the initiation and exacerbation of neuroinflammation.}, } @article {pmid29358391, year = {2018}, author = {Adam, PS and Borrel, G and Gribaldo, S}, title = {Evolutionary history of carbon monoxide dehydrogenase/acetyl-CoA synthase, one of the oldest enzymatic complexes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1166-E1173}, pmid = {29358391}, issn = {1091-6490}, mesh = {Acetate-CoA Ligase/*genetics/metabolism ; Aldehyde Oxidoreductases/*genetics/metabolism ; Archaea/*enzymology/genetics ; Bacteria/*enzymology/genetics ; *Biological Evolution ; Carbon Cycle ; Carbon Monoxide/metabolism ; Genome, Archaeal ; Genome, Bacterial ; Multienzyme Complexes/*genetics/metabolism ; *Phylogeny ; }, abstract = {Carbon monoxide dehydrogenase/acetyl-CoA synthase (CODH/ACS) is a five-subunit enzyme complex responsible for the carbonyl branch of the Wood-Ljungdahl (WL) pathway, considered one of the most ancient metabolisms for anaerobic carbon fixation, but its origin and evolutionary history have been unclear. While traditionally associated with methanogens and acetogens, the presence of CODH/ACS homologs has been reported in a large number of uncultured anaerobic lineages. Here, we have carried out an exhaustive phylogenomic study of CODH/ACS in over 6,400 archaeal and bacterial genomes. The identification of complete and likely functional CODH/ACS complexes in these genomes significantly expands its distribution in microbial lineages. The CODH/ACS complex displays astounding conservation and vertical inheritance over geological times. Rare intradomain and interdomain transfer events might tie into important functional transitions, including the acquisition of CODH/ACS in some archaeal methanogens not known to fix carbon, the tinkering of the complex in a clade of model bacterial acetogens, or emergence of archaeal-bacterial hybrid complexes. Once these transfers were clearly identified, our results allowed us to infer the presence of a CODH/ACS complex with at least four subunits in the last universal common ancestor (LUCA). Different scenarios on the possible role of ancestral CODH/ACS are discussed. Despite common assumptions, all are equally compatible with an autotrophic, mixotrophic, or heterotrophic LUCA. Functional characterization of CODH/ACS from a larger spectrum of bacterial and archaeal lineages and detailed evolutionary analysis of the WL methyl branch will help resolve this issue.}, } @article {pmid29358390, year = {2018}, author = {Wutz, A and Melcher, D and Samaha, J}, title = {Frequency modulation of neural oscillations according to visual task demands.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1346-1351}, pmid = {29358390}, issn = {1091-6490}, mesh = {Adult ; Algorithms ; Attention/physiology ; Cerebral Cortex/*physiology ; Female ; Fourier Analysis ; Humans ; *Magnetoencephalography ; Male ; Nontherapeutic Human Experimentation ; Periodicity ; Photic Stimulation ; Psychometrics ; Signal Processing, Computer-Assisted ; Visual Perception/*physiology ; }, abstract = {Temporal integration in visual perception is thought to occur within cycles of occipital alpha-band (8-12 Hz) oscillations. Successive stimuli may be integrated when they fall within the same alpha cycle and segregated for different alpha cycles. Consequently, the speed of alpha oscillations correlates with the temporal resolution of perception, such that lower alpha frequencies provide longer time windows for perceptual integration and higher alpha frequencies correspond to faster sampling and segregation. Can the brain's rhythmic activity be dynamically controlled to adjust its processing speed according to different visual task demands? We recorded magnetoencephalography (MEG) while participants switched between task instructions for temporal integration and segregation, holding stimuli and task difficulty constant. We found that the peak frequency of alpha oscillations decreased when visual task demands required temporal integration compared with segregation. Alpha frequency was strategically modulated immediately before and during stimulus processing, suggesting a preparatory top-down source of modulation. Its neural generators were located in occipital and inferotemporal cortex. The frequency modulation was specific to alpha oscillations and did not occur in the delta (1-3 Hz), theta (3-7 Hz), beta (15-30 Hz), or gamma (30-50 Hz) frequency range. These results show that alpha frequency is under top-down control to increase or decrease the temporal resolution of visual perception.}, } @article {pmid29358389, year = {2018}, author = {Le Bris, A and Mills, KE and Wahle, RA and Chen, Y and Alexander, MA and Allyn, AJ and Schuetz, JG and Scott, JD and Pershing, AJ}, title = {Climate vulnerability and resilience in the most valuable North American fishery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1831-1836}, pmid = {29358389}, issn = {1091-6490}, mesh = {Animals ; Atlantic Ocean ; Climate Change/*economics ; Fisheries/*economics ; *Nephropidae ; North America ; }, abstract = {Managing natural resources in an era of increasing climate impacts requires accounting for the synergistic effects of climate, ecosystem changes, and harvesting on resource productivity. Coincident with recent exceptional warming of the northwest Atlantic Ocean and removal of large predatory fish, the American lobster has become the most valuable fishery resource in North America. Using a model that links ocean temperature, predator density, and fishing to population productivity, we show that harvester-driven conservation efforts to protect large lobsters prepared the Gulf of Maine lobster fishery to capitalize on favorable ecosystem conditions, resulting in the record-breaking landings recently observed in the region. In contrast, in the warmer southern New England region, the absence of similar conservation efforts precipitated warming-induced recruitment failure that led to the collapse of the fishery. Population projections under expected warming suggest that the American lobster fishery is vulnerable to future temperature increases, but continued efforts to preserve the stock's reproductive potential can dampen the negative impacts of warming. This study demonstrates that, even though global climate change is severely impacting marine ecosystems, widely adopted, proactive conservation measures can increase the resilience of commercial fisheries to climate change.}, } @article {pmid29358388, year = {2018}, author = {Meindl, RS and Chaney, ME and Lovejoy, CO}, title = {Early hominids may have been weed species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1244-1249}, pmid = {29358388}, issn = {1091-6490}, mesh = {Africa ; Animals ; Behavior, Animal ; Ecosystem ; Female ; Fertility/*physiology ; Forests ; Fossils ; Haplorhini/physiology ; Hominidae/anatomy & histology/*physiology ; Macaca/physiology ; Male ; Mortality ; Social Behavior ; }, abstract = {Panid, gorillid, and hominid social structures appear to have diverged as dramatically as did their locomotor patterns as they emerged from a late Miocene last common ancestor (LCA). Despite their elimination of the sectorial canine complex and adoption of bipedality with its attendant removal of their ready access to the arboreal canopy, Australopithecus was able to easily invade novel habitats after florescence from its likely ancestral genus, Ardipithecus sp. Other hominoids, unable to sustain sufficient population growth, began an inexorable decline, culminating in their restriction to modern refugia. Success similar to that of earliest hominids also characterizes several species of macaques, often termed "weed species." We here review their most salient demographic features and find that a key element is irregularly elevated female survival. It is reasonable to conclude that a similar feature characterized early hominids, most likely made possible by the adoption of social monogamy. Reduced female mortality is a more probable key to early hominid success than a reduction in birth space, which would have been physiologically more difficult.}, } @article {pmid29358387, year = {2018}, author = {French, JR and Friedrich, K and Tessendorf, SA and Rauber, RM and Geerts, B and Rasmussen, RM and Xue, L and Kunkel, ML and Blestrud, DR}, title = {Precipitation formation from orographic cloud seeding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1168-1173}, pmid = {29358387}, issn = {1091-6490}, abstract = {Throughout the western United States and other semiarid mountainous regions across the globe, water supplies are fed primarily through the melting of snowpack. Growing populations place higher demands on water, while warmer winters and earlier springs reduce its supply. Water managers are tantalized by the prospect of cloud seeding as a way to increase winter snowfall, thereby shifting the balance between water supply and demand. Little direct scientific evidence exists that confirms even the basic physical hypothesis upon which cloud seeding relies. The intent of glaciogenic seeding of orographic clouds is to introduce aerosol into a cloud to alter the natural development of cloud particles and enhance wintertime precipitation in a targeted region. The hypothesized chain of events begins with the introduction of silver iodide aerosol into cloud regions containing supercooled liquid water, leading to the nucleation of ice crystals, followed by ice particle growth to sizes sufficiently large such that snow falls to the ground. Despite numerous experiments spanning several decades, no direct observations of this process exist. Here, measurements from radars and aircraft-mounted cloud physics probes are presented that together show the initiation, growth, and fallout to the mountain surface of ice crystals resulting from glaciogenic seeding. These data, by themselves, do not address the question of cloud seeding efficacy, but rather form a critical set of observations necessary for such investigations. These observations are unambiguous and provide details of the physical chain of events following the introduction of glaciogenic cloud seeding aerosol into supercooled liquid orographic clouds.}, } @article {pmid29358386, year = {2018}, author = {Ravindran, S}, title = {Profile of Steve Granick.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1400-1402}, pmid = {29358386}, issn = {1091-6490}, } @article {pmid29358385, year = {2018}, author = {Brooks, AM and Sabrina, S and Bishop, KJM}, title = {Shape-directed dynamics of active colloids powered by induced-charge electrophoresis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1090-E1099}, pmid = {29358385}, issn = {1091-6490}, abstract = {The symmetry and shape of colloidal particles can direct complex particle motions through fluid environments powered by simple energy inputs. The ability to rationally design or "program" the dynamics of such active colloids is an important step toward the realization of colloidal machines, in which components assemble spontaneously in space and time to perform dynamic (dissipative) functions such as actuation and transport. Here, we systematically investigate the dynamics of polarizable particles of different shapes moving in an oscillating electric field via induced-charge electrophoresis (ICEP). We consider particles from each point group in three dimensions (3D) and identify the different rotational and translational motions allowed by symmetry. We describe how the 3D shape of rigid particles can be tailored to achieve desired dynamics including oscillatory motions, helical trajectories, and complex periodic orbits. The methodology we develop is generally applicable to the design of shape-directed particle motions powered by other energy inputs.}, } @article {pmid29358384, year = {2018}, author = {Harpold, AA and Brooks, PD}, title = {Humidity determines snowpack ablation under a warming climate.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1215-1220}, pmid = {29358384}, issn = {1091-6490}, abstract = {Climate change is altering historical patterns of snow accumulation and melt, threatening societal frameworks for water supply. However, decreases in spring snow water equivalent (SWE) and changes in snowmelt are not ubiquitous despite widespread warming in the western United States, highlighting the importance of latent and radiant energy fluxes in snow ablation. Here we demonstrate how atmospheric humidity and solar radiation interact with warming temperature to control snowpack ablation at 462 sites spanning a gradient in mean winter temperature from -8.9 to +2.9 °C. The most widespread response to warming was an increase in episodic, midwinter ablation events. Under humid conditions these ablation events were dominated by melt, averaging 21% (202 mm/year) of SWE. Winter ablation under dry atmospheric conditions at similar temperatures was smaller, averaging 12% (58 mm/year) of SWE and likely dominated by sublimation fluxes. These contrasting patterns result from the critical role that atmospheric humidity plays in local energy balance, with latent and longwave radiant fluxes cooling the snowpack under dry conditions and warming it under humid conditions. Similarly, spring melt rates were faster under humid conditions, yet the second most common trend was a reduction in spring melt rates associated with earlier initiation when solar radiation inputs are smaller. Our analyses demonstrate that regional differences in atmospheric humidity are a major cause of the spatial variability in snowpack response to warming. Better constraints on humidity will be critical to predicting both the amount and timing of surface water supplies under climate change.}, } @article {pmid29358383, year = {2018}, author = {Karl, T and Striednig, M and Graus, M and Hammerle, A and Wohlfahrt, G}, title = {Urban flux measurements reveal a large pool of oxygenated volatile organic compound emissions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1186-1191}, pmid = {29358383}, issn = {1091-6490}, abstract = {Atmospheric chemistry is fueled by a large annual influx of nonmethane volatile organic compounds (NMVOC). These compounds influence ozone formation, lead to secondary organic aerosol production, and play a significant role for the oxidizing capacity of the atmosphere. The anthropogenic NMVOC budget is considerably uncertain due to the diversity of urban emission sources. Here, we present comprehensive observations of urban NMVOC eddy covariance fluxes using a newly designed proton-transfer-reaction quadrupole interface time-of-flight mass spectrometer. We found emission fluxes of a surprisingly large pool of oxygenated NMVOCs (OVOCs) with an appreciable fraction of higher oxidized OVOCs that cannot be explained by known fast photochemical turnaround or current primary emission estimates. Measured OVOC/NMVOC bulk flux ratios are two to four times higher than inferred from aggregated anthropogenic emission inventories. Extrapolating these results would double the global anthropogenic NMVOC flux. In view of globally accelerating urbanization, our study highlights the need to reevaluate the influence of anthropogenic NMVOC on atmospheric chemistry, human health, and the climate system.}, } @article {pmid29358382, year = {2018}, author = {Kim, BJ and Kim, SH}, title = {Prediction of inherited genomic susceptibility to 20 common cancer types by a supervised machine-learning method.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1322-1327}, pmid = {29358382}, issn = {1091-6490}, mesh = {*Genetic Predisposition to Disease ; Genome, Human ; Humans ; Life Style ; *Machine Learning ; Neoplasms/*genetics ; *Polymorphism, Single Nucleotide ; Probability ; }, abstract = {Prevention and early intervention are the most effective ways of avoiding or minimizing psychological, physical, and financial suffering from cancer. However, such proactive action requires the ability to predict the individual's susceptibility to cancer with a measure of probability. Of the triad of cancer-causing factors (inherited genomic susceptibility, environmental factors, and lifestyle factors), the inherited genomic component may be derivable from the recent public availability of a large body of whole-genome variation data. However, genome-wide association studies have so far showed limited success in predicting the inherited susceptibility to common cancers. We present here a multiple classification approach for predicting individuals' inherited genomic susceptibility to acquire the most likely phenotype among a panel of 20 major common cancer types plus 1 "healthy" type by application of a supervised machine-learning method under competing conditions among the cohorts of the 21 types. This approach suggests that, depending on the phenotypes of 5,919 individuals of "white" ethnic population in this study, (i) the portion of the cohort of a cancer type who acquired the observed type due to mostly inherited genomic susceptibility factors ranges from about 33 to 88% (or its corollary: the portion due to mostly environmental and lifestyle factors ranges from 12 to 67%), and (ii) on an individual level, the method also predicts individuals' inherited genomic susceptibility to acquire the other types ranked with associated probabilities. These probabilities may provide practical information for individuals, heath professionals, and health policymakers related to prevention and/or early intervention of cancer.}, } @article {pmid29358381, year = {2018}, author = {Dong, YW and Liao, ML and Meng, XL and Somero, GN}, title = {Structural flexibility and protein adaptation to temperature: Molecular dynamics analysis of malate dehydrogenases of marine molluscs.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1274-1279}, pmid = {29358381}, issn = {1091-6490}, mesh = {Animals ; Binding Sites ; Malate Dehydrogenase/*chemistry/metabolism ; Molecular Dynamics Simulation ; Mollusca/*enzymology ; Protein Denaturation ; Temperature ; }, abstract = {Orthologous proteins of species adapted to different temperatures exhibit differences in stability and function that are interpreted to reflect adaptive variation in structural "flexibility." However, quantifying flexibility and comparing flexibility across proteins has remained a challenge. To address this issue, we examined temperature effects on cytosolic malate dehydrogenase (cMDH) orthologs from differently thermally adapted congeners of five genera of marine molluscs whose field body temperatures span a range of ∼60 °C. We describe consistent patterns of convergent evolution in adaptation of function [temperature effects on KM of cofactor (NADH)] and structural stability (rate of heat denaturation of activity). To determine how these differences depend on flexibilities of overall structure and of regions known to be important in binding and catalysis, we performed molecular dynamics simulation (MDS) analyses. MDS analyses revealed a significant negative correlation between adaptation temperature and heat-induced increase of backbone atom movements [root mean square deviation (rmsd) of main-chain atoms]. Root mean square fluctuations (RMSFs) of movement by individual amino acid residues varied across the sequence in a qualitatively similar pattern among orthologs. Regions of sequence involved in ligand binding and catalysis-termed mobile regions 1 and 2 (MR1 and MR2), respectively-showed the largest values for RMSF. Heat-induced changes in RMSF values across the sequence and, importantly, in MR1 and MR2 were greatest in cold-adapted species. MDS methods are shown to provide powerful tools for examining adaptation of enzymes by providing a quantitative index of protein flexibility and identifying sequence regions where adaptive change in flexibility occurs.}, } @article {pmid29358380, year = {2018}, author = {Faoro, R and Bassu, M and Mejia, YX and Stephan, T and Dudani, N and Boeker, C and Jakobs, S and Burg, TP}, title = {Aberration-corrected cryoimmersion light microscopy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1204-1209}, pmid = {29358380}, issn = {1091-6490}, mesh = {Cell Line ; Equipment Design ; Escherichia coli/cytology/genetics ; Fluorescent Dyes/chemistry ; Freezing ; Green Fluorescent Proteins/genetics/metabolism ; Histological Techniques/*methods ; Humans ; Image Processing, Computer-Assisted ; Microscopy/instrumentation/*methods ; Microscopy, Fluorescence/methods ; Photobleaching ; Refractometry ; Yeasts/cytology/genetics ; }, abstract = {Cryogenic fluorescent light microscopy of flash-frozen cells stands out by artifact-free fixation and very little photobleaching of the fluorophores used. To attain the highest level of resolution, aberration-free immersion objectives with accurately matched immersion media are required, but both do not exist for imaging below the glass-transition temperature of water. Here, we resolve this challenge by combining a cryoimmersion medium, HFE-7200, which matches the refractive index of room-temperature water, with a technological concept in which the body of the objective and the front lens are not in thermal equilibrium. We implemented this concept by replacing the metallic front-lens mount of a standard bioimaging water immersion objective with an insulating ceramic mount heated around its perimeter. In this way, the objective metal housing can be maintained at room temperature, while creating a thermally shielded cold microenvironment around the sample and front lens. To demonstrate the range of potential applications, we show that our method can provide superior contrast in Escherichia coli and yeast cells expressing fluorescent proteins and resolve submicrometer structures in multicolor immunolabeled human bone osteosarcoma epithelial (U2OS) cells at [Formula: see text]C.}, } @article {pmid29358379, year = {2018}, author = {Souma, T and Thomson, BR and Heinen, S and Carota, IA and Yamaguchi, S and Onay, T and Liu, P and Ghosh, AK and Li, C and Eremina, V and Hong, YK and Economides, AN and Vestweber, D and Peters, KG and Jin, J and Quaggin, SE}, title = {Context-dependent functions of angiopoietin 2 are determined by the endothelial phosphatase VEPTP.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1298-1303}, pmid = {29358379}, issn = {1091-6490}, support = {P30 CA060553/CA/NCI NIH HHS/United States ; R01 EY025799/EY/NEI NIH HHS/United States ; R01 HL124120/HL/NHLBI NIH HHS/United States ; T32 DK108738/DK/NIDDK NIH HHS/United States ; }, mesh = {Angiopoietin-1/genetics/metabolism ; Angiopoietin-2/genetics/*metabolism ; Animals ; Endothelium, Lymphatic/embryology/metabolism ; Endothelium, Vascular/metabolism ; HEK293 Cells ; Humans ; Mice, Knockout ; Mice, Transgenic ; Receptor, TIE-2/metabolism ; Receptor-Like Protein Tyrosine Phosphatases, Class 3/genetics/*metabolism ; Signal Transduction ; }, abstract = {The angiopoietin (ANGPT)-TIE2/TEK signaling pathway is essential for blood and lymphatic vascular homeostasis. ANGPT1 is a potent TIE2 activator, whereas ANGPT2 functions as a context-dependent agonist/antagonist. In disease, ANGPT2-mediated inhibition of TIE2 in blood vessels is linked to vascular leak, inflammation, and metastasis. Using conditional knockout studies in mice, we show TIE2 is predominantly activated by ANGPT1 in the cardiovascular system and by ANGPT2 in the lymphatic vasculature. Mechanisms underlying opposing actions of ANGPT2 in blood vs. lymphatic endothelium are poorly understood. Here we show the endothelial-specific phosphatase VEPTP (vascular endothelial protein tyrosine phosphatase) determines TIE2 response to ANGPT2. VEPTP is absent from lymphatic endothelium in mouse in vivo, permitting ANGPT2/TIE2-mediated lymphangiogenesis. Inhibition of VEPTP converts ANGPT2 into a potent TIE2 activator in blood endothelium. Our data support a model whereby VEPTP functions as a rheostat to modulate ANGPT2 ligand effect on TIE2.}, } @article {pmid29358378, year = {2018}, author = {Ferreira, R and Teixeira, PG and Siewers, V and Nielsen, J}, title = {Redirection of lipid flux toward phospholipids in yeast increases fatty acid turnover and secretion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1262-1267}, pmid = {29358378}, issn = {1091-6490}, mesh = {Acyl Coenzyme A/genetics/metabolism ; Acyl-CoA Oxidase/genetics/metabolism ; Coenzyme A Ligases/genetics/metabolism ; Fatty Acids/*metabolism ; Gene Deletion ; Gene Expression Regulation, Fungal ; *Lipid Metabolism/genetics ; Lysophospholipase/genetics/metabolism ; Membrane Lipids/biosynthesis/genetics ; Membrane Proteins/genetics/metabolism ; Phosphatidate Phosphatase/genetics/metabolism ; Phospholipids/metabolism ; Saccharomyces cerevisiae/genetics/*metabolism ; Saccharomyces cerevisiae Proteins/genetics/metabolism ; }, abstract = {Bio-based production of fatty acids and fatty acid-derived products can enable sustainable substitution of petroleum-derived fuels and chemicals. However, developing new microbial cell factories for producing high levels of fatty acids requires extensive engineering of lipid metabolism, a complex and tightly regulated metabolic network. Here we generated a Saccharomyces cerevisiae platform strain with a simplified lipid metabolism network with high-level production of free fatty acids (FFAs) due to redirected fatty acid metabolism and reduced feedback regulation. Deletion of the main fatty acid activation genes (the first step in β-oxidation), main storage lipid formation genes, and phosphatidate phosphatase genes resulted in a constrained lipid metabolic network in which fatty acid flux was directed to a large extent toward phospholipids. This resulted in simultaneous increases of phospholipids by up to 2.8-fold and of FFAs by up to 40-fold compared with wild-type levels. Further deletion of phospholipase genes PLB1 and PLB2 resulted in a 46% decrease in FFA levels and 105% increase in phospholipid levels, suggesting that phospholipid hydrolysis plays an important role in FFA production when phospholipid levels are increased. The multiple deletion mutant generated allowed for a study of fatty acid dynamics in lipid metabolism and represents a platform strain with interesting properties that provide insight into the future development of lipid-related cell factories.}, } @article {pmid29358377, year = {2018}, author = {Wang, Y and Wang, L and Xu, Q and Liu, D and Chen, L and Troje, NF and He, S and Jiang, Y}, title = {Heritable aspects of biological motion perception and its covariation with autistic traits.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1937-1942}, pmid = {29358377}, issn = {1091-6490}, mesh = {Autism Spectrum Disorder/*genetics ; Humans ; Motion Perception/*physiology ; Twins ; }, abstract = {The ability to detect biological motion (BM) and decipher the meaning therein is essential to human survival and social interaction. However, at the individual level, we are not equally equipped with this ability. In particular, impaired BM perception and abnormal neural responses to BM have been observed in autism spectrum disorder (ASD), a highly heritable neurodevelopmental disorder characterized by devastating social deficits. Here, we examined the underlying sources of individual differences in two abilities fundamental to BM perception (i.e., the abilities to process local kinematic and global configurational information of BM) and explored whether BM perception shares a common genetic origin with autistic traits. Using the classical twin method, we found reliable genetic influences on BM perception and revealed a clear dissociation between its two components-whereas genes account for about 50% of the individual variation in local BM processing, global BM processing is largely shaped by environment. Critically, participants' sensitivity to local BM cues was negatively correlated with their autistic traits through the dimension of social communication, with the covariation largely mediated by shared genetic effects. These findings demonstrate that the ability to process BM, especially with regard to its inherent kinetics, is heritable. They also advance our understanding of the sources of the linkage between autistic symptoms and BM perception deficits, opening up the possibility of treating the ability to process local BM information as a distinct hallmark of social cognition.}, } @article {pmid29358376, year = {2018}, author = {Mentes, A and Huehn, A and Liu, X and Zwolak, A and Dominguez, R and Shuman, H and Ostap, EM and Sindelar, CV}, title = {High-resolution cryo-EM structures of actin-bound myosin states reveal the mechanism of myosin force sensing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1292-1297}, pmid = {29358376}, issn = {1091-6490}, support = {R01 GM073791/GM/NIGMS NIH HHS/United States ; R01 GM110530/GM/NIGMS NIH HHS/United States ; R37 GM057247/GM/NIGMS NIH HHS/United States ; T32 GM008283/GM/NIGMS NIH HHS/United States ; }, mesh = {Actins/*chemistry/*metabolism ; Actomyosin/chemistry/metabolism ; Adenosine Diphosphate/metabolism ; Binding Sites ; Catalytic Domain ; Cryoelectron Microscopy/*methods ; Crystallography, X-Ray ; Models, Molecular ; Molecular Dynamics Simulation ; Myosin Type I/*chemistry/*metabolism ; Phalloidine/chemistry/metabolism ; Protein Conformation ; }, abstract = {Myosins adjust their power outputs in response to mechanical loads in an isoform-dependent manner, resulting in their ability to dynamically adapt to a range of motile challenges. Here, we reveal the structural basis for force-sensing based on near-atomic resolution structures of one rigor and two ADP-bound states of myosin-IB (myo1b) bound to actin, determined by cryo-electron microscopy. The two ADP-bound states are separated by a 25° rotation of the lever. The lever of the first ADP state is rotated toward the pointed end of the actin filament and forms a previously unidentified interface with the N-terminal subdomain, which constitutes the upper half of the nucleotide-binding cleft. This pointed-end orientation of the lever blocks ADP release by preventing the N-terminal subdomain from the pivoting required to open the nucleotide binding site, thus revealing how myo1b is inhibited by mechanical loads that restrain lever rotation. The lever of the second ADP state adopts a rigor-like orientation, stabilized by class-specific elements of myo1b. We identify a role for this conformation as an intermediate in the ADP release pathway. Moreover, comparison of our structures with other myosins reveals structural diversity in the actomyosin binding site, and we reveal the high-resolution structure of actin-bound phalloidin, a potent stabilizer of filamentous actin. These results provide a framework to understand the spectrum of force-sensing capacities among the myosin superfamily.}, } @article {pmid29358375, year = {2018}, author = {Raanan, H and Pike, DH and Moore, EK and Falkowski, PG and Nanda, V}, title = {Modular origins of biological electron transfer chains.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1280-1285}, pmid = {29358375}, issn = {1091-6490}, mesh = {Bacterial Proteins/chemistry/metabolism ; Coenzymes/chemistry/*metabolism ; Cytochromes c/chemistry/metabolism ; Electron Transport ; *Evolution, Molecular ; Ferredoxins/chemistry/metabolism ; Metals/chemistry/metabolism ; Models, Molecular ; Oxidoreductases/*chemistry/*metabolism ; Plastocyanin/chemistry/metabolism ; Protein Conformation ; Structural Homology, Protein ; }, abstract = {Oxidoreductases catalyze electron transfer reactions that ultimately provide the energy for life. A limited set of ancestral protein-metal modules are presumably the building blocks that evolved into this diverse protein family. However, the identity of these modules and their path to modern oxidoreductases is unknown. Using a comparative structural analysis approach, we identify a set of fundamental electron transfer modules that have evolved to form the extant oxidoreductases. Using transition metal-containing cofactors as fiducial markers, it is possible to cluster cofactor microenvironments into as few as four major modules: bacterial ferredoxin, cytochrome c, symerythrin, and plastocyanin-type folds. From structural alignments, it is challenging to ascertain whether modules evolved from a single common ancestor (homology) or arose by independent convergence on a limited set of structural forms (analogy). Additional insight into common origins is contained in the spatial adjacency network (SPAN), which is based on proximity of modules in oxidoreductases containing multiple cofactor electron transfer chains. Electron transfer chains within complex modern oxidoreductases likely evolved through repeated duplication and diversification of ancient modular units that arose in the Archean eon.}, } @article {pmid29358374, year = {2018}, author = {Evans, D and Sagoo, N and Renema, W and Cotton, LJ and Müller, W and Todd, JA and Saraswati, PK and Stassen, P and Ziegler, M and Pearson, PN and Valdes, PJ and Affek, HP}, title = {Eocene greenhouse climate revealed by coupled clumped isotope-Mg/Ca thermometry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1174-1179}, pmid = {29358374}, issn = {1091-6490}, abstract = {Past greenhouse periods with elevated atmospheric CO2 were characterized by globally warmer sea-surface temperatures (SST). However, the extent to which the high latitudes warmed to a greater degree than the tropics (polar amplification) remains poorly constrained, in particular because there are only a few temperature reconstructions from the tropics. Consequently, the relationship between increased CO2, the degree of tropical warming, and the resulting latitudinal SST gradient is not well known. Here, we present coupled clumped isotope (Δ47)-Mg/Ca measurements of foraminifera from a set of globally distributed sites in the tropics and midlatitudes. Δ47 is insensitive to seawater chemistry and therefore provides a robust constraint on tropical SST. Crucially, coupling these data with Mg/Ca measurements allows the precise reconstruction of Mg/Casw throughout the Eocene, enabling the reinterpretation of all planktonic foraminifera Mg/Ca data. The combined dataset constrains the range in Eocene tropical SST to 30-36 °C (from sites in all basins). We compare these accurate tropical SST to deep-ocean temperatures, serving as a minimum constraint on high-latitude SST. This results in a robust conservative reconstruction of the early Eocene latitudinal gradient, which was reduced by at least 32 ± 10% compared with present day, demonstrating greater polar amplification than captured by most climate models.}, } @article {pmid29358373, year = {2018}, author = {Ghosh, A and Garee, G and Sweeny, EA and Nakamura, Y and Stuehr, DJ}, title = {Hsp90 chaperones hemoglobin maturation in erythroid and nonerythroid cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1117-E1126}, pmid = {29358373}, issn = {1091-6490}, support = {P01 HL081064/HL/NHLBI NIH HHS/United States ; R01 GM051491/GM/NIGMS NIH HHS/United States ; R01 GM097041/GM/NIGMS NIH HHS/United States ; }, mesh = {Blood Proteins/metabolism ; Cell Differentiation ; Cell Proliferation ; Cells, Cultured ; Erythroid Precursor Cells/cytology/*metabolism ; Erythropoiesis/*physiology ; HSP90 Heat-Shock Proteins/*metabolism ; Heme/chemistry/*metabolism ; Hemoglobins/*biosynthesis/chemistry ; Humans ; Lung/cytology/*metabolism ; Macrophages/cytology/*metabolism ; Molecular Chaperones/metabolism ; Protein Binding ; }, abstract = {Maturation of adult (α2β2) and fetal hemoglobin (α2γ2) tetramers requires that heme be incorporated into each globin. While hemoglobin alpha (Hb-α) relies on a specific erythroid chaperone (alpha Hb-stabilizing protein, AHSP), the other chaperones that may help mature the partner globins (Hb-γ or Hb-β) in erythroid cells, or may enable nonerythroid cells to express mature Hb, are unknown. We investigated a role for heat-shock protein 90 (hsp90) in Hb maturation in erythroid precursor cells that naturally express Hb-α with either Hb-γ (K562 and HiDEP-1 cells) or Hb-β (HUDEP-2) and in nonerythroid cell lines that either endogenously express Hb-αβ (RAW and A549) or that we transfected to express the globins. We found the following: (i) AHSP and hsp90 associate with distinct globin partners in their immature heme-free states (AHSP with apo-Hbα, and hsp90 with apo-Hbβ or Hb-γ) and that hsp90 does not associate with mature Hb. (ii) Hsp90 stabilizes the apo-globins and helps to drive their heme insertion reactions, as judged by pharmacologic hsp90 inhibition or by coexpression of an ATP-ase defective hsp90. (iii) In nonerythroid cells, heme insertion into all globins became hsp90-dependent, which may explain how mixed Hb tetramers can mature in cells that do not express AHSP. Together, our findings uncover a process in which hsp90 first binds to immature, heme-free Hb-γ or Hb-β, drives their heme insertion process, and then dissociates to allow their heterotetramer formation with Hb-α. Thus, in driving heme insertion, hsp90 works in concert with AHSP to generate functional Hb tetramers during erythropoiesis.}, } @article {pmid29358372, year = {2018}, author = {Haddad, J and Pontoni, D and Murphy, BM and Festersen, S and Runge, B and Magnussen, OM and Steinrück, HG and Reichert, H and Ocko, BM and Deutsch, M}, title = {Surface structure evolution in a homologous series of ionic liquids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1100-E1107}, pmid = {29358372}, issn = {1091-6490}, abstract = {Interfaces of room temperature ionic liquids (RTILs) are important for both applications and basic science and are therefore intensely studied. However, the evolution of their interface structure with the cation's alkyl chain length [Formula: see text] from Coulomb to van der Waals interaction domination has not yet been studied for even a single broad homologous RTIL series. We present here such a study of the liquid-air interface for [Formula: see text], using angstrom-resolution X-ray methods. For [Formula: see text], a typical "simple liquid" monotonic surface-normal electron density profile [Formula: see text] is obtained, like those of water and organic solvents. For [Formula: see text], increasingly more pronounced nanoscale self-segregation of the molecules' charged moieties and apolar chains yields surface layering with alternating regions of headgroups and chains. The layering decays into the bulk over a few, to a few tens, of nanometers. The layering periods and decay lengths, their linear [Formula: see text] dependence, and slopes are discussed within two models, one with partial-chain interdigitation and the other with liquid-like chains. No surface-parallel long-range order is found within the surface layer. For [Formula: see text], a different surface phase is observed above melting. Our results also impact general liquid-phase issues like supramolecular self-aggregation and bulk-surface structure relations.}, } @article {pmid29358371, year = {2018}, author = {Fiori, F and Longo, MR}, title = {Tactile distance illusions reflect a coherent stretch of tactile space.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1238-1243}, pmid = {29358371}, issn = {1091-6490}, mesh = {Forehead ; Hand ; Humans ; Illusions/*physiology ; Models, Biological ; Nontherapeutic Human Experimentation ; Skin ; Space Perception ; Touch/*physiology ; Touch Perception/*physiology ; }, abstract = {Illusions of the perception of distance between two touches on the skin have been described since the classic work of Weber in the 19th century. The perceptual mechanisms underlying such spatial distortions, however, remain poorly understood. One potential interpretation is that the representational space of touch is related to the true structure of the skin by a geometrically simple stretch. If distortions of tactile distance perception reflect a simple stretch of tactile space, perceived distance should vary predictably as a function of the orientation of the stimulus on the skin, showing a sinusoidal pattern. Here, we tested this prediction by obtained judgments of perceived tactile distance for pairs of touches aligned with eight orientations on the skin. Across four experiments, the results were highly consistent with this prediction, showing no apparent deviation from a model of simple stretch of tactile space. Similar results were apparent on both the dorsum and palm of the hand, as well as the forehead. These results show that spatial distortions of touch are well characterized by a geometrically simple stretch of tactile space.}, } @article {pmid29358370, year = {2018}, author = {Higa, M and Oka, M and Fujihara, Y and Masuda, K and Yoneda, Y and Kishimoto, T}, title = {Regulation of inflammatory responses by dynamic subcellular localization of RNA-binding protein Arid5a.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1214-E1220}, pmid = {29358370}, issn = {1091-6490}, mesh = {Active Transport, Cell Nucleus ; Animals ; Cell Nucleus/*metabolism ; Cytokines/*metabolism ; Cytoplasm/*metabolism ; DNA-Binding Proteins/*physiology ; Female ; HeLa Cells ; Humans ; Inflammation/chemically induced/*immunology/metabolism/pathology ; Lipopolysaccharides/pharmacology ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; Ribonucleases/*metabolism ; Subcellular Fractions ; Transcription Factors/*physiology ; }, abstract = {Adenine-thymine (AT)-rich interactive domain 5a (Arid5a) is an RNA-binding protein found in the cytoplasm and nucleus of normally growing cells. Although Arid5a is known to play an important role in immune regulation, whether and how Arid5a subcellular localization impacts immune regulation has remained unclear. In this study, we generated Arid5a transgenic (TG) mice to address this question. While ectopic Arid5a overexpression did not affect expression of inflammatory cytokines under unstimulated conditions, significantly higher levels of inflammatory cytokines, such as IL-6, were produced in response to lipopolysaccharide (LPS) stimulation. Consistent with this, TG mice were more sensitive to LPS treatment than wild-type mice. We also found that Arid5a is imported into the nucleus via a classical importin-α/β1-mediated pathway. On stimulation, nuclear Arid5a levels were decreased, while there was a concomitant increase in cytoplasmic Arid5a. Arid5a is associated with up-frameshift protein 1, and its nuclear export is regulated by a nuclear export receptor, chromosomal region maintenance 1. Taken together, these data indicate that Arid5a is a dynamic protein that translocates to the cytoplasm from the nucleus so as to properly exert its dual function in mRNA stabilization and transcriptional regulation during inflammatory conditions.}, } @article {pmid29358369, year = {2018}, author = {Raghanti, MA and Edler, MK and Stephenson, AR and Munger, EL and Jacobs, B and Hof, PR and Sherwood, CC and Holloway, RL and Lovejoy, CO}, title = {A neurochemical hypothesis for the origin of hominids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1108-E1116}, pmid = {29358369}, issn = {1091-6490}, support = {P30 AG013854/AG/NIA NIH HHS/United States ; R24 NS092988/NS/NINDS NIH HHS/United States ; P51 RR000166/RR/NCRR NIH HHS/United States ; R44 AG014308/AG/NIA NIH HHS/United States ; U42 OD011158/OD/NIH HHS/United States ; }, mesh = {Altruism ; Animals ; *Biological Evolution ; Corpus Striatum/*physiology ; Dogs ; Humans ; *Neurochemistry ; Personality ; Primates ; *Selection, Genetic ; *Social Behavior ; Social Conformity ; }, abstract = {It has always been difficult to account for the evolution of certain human characters such as language, empathy, and altruism via individual reproductive success. However, the striatum, a subcortical region originally thought to be exclusively motor, is now known to contribute to social behaviors and "personality styles" that may link such complexities with natural selection. We here report that the human striatum exhibits a unique neurochemical profile that differs dramatically from those of other primates. The human signature of elevated striatal dopamine, serotonin, and neuropeptide Y, coupled with lowered acetylcholine, systematically favors externally driven behavior and greatly amplifies sensitivity to social cues that promote social conformity, empathy, and altruism. We propose that selection induced an initial form of this profile in early hominids, which increased their affiliative behavior, and that this shift either preceded or accompanied the adoption of bipedality and elimination of the sectorial canine. We further hypothesize that these changes were critical for increased individual fitness and promoted the adoption of social monogamy, which progressively increased cooperation as well as a dependence on tradition-based cultural transmission. These eventually facilitated the acquisition of language by elevating the reproductive advantage afforded those most sensitive to social cues.}, } @article {pmid29358368, year = {2018}, author = {Tsai, CT and Robinson, PV and Cortez, FJ and Elma, MLB and Seftel, D and Pourmandi, N and Pandori, MW and Bertozzi, CR}, title = {Antibody detection by agglutination-PCR (ADAP) enables early diagnosis of HIV infection by oral fluid analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1250-1255}, pmid = {29358368}, issn = {1091-6490}, support = {R21 DK108781/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Agglutination ; DNA/chemistry ; Early Diagnosis ; HIV Antibodies/analysis/*genetics ; HIV Core Protein p24/genetics ; HIV Envelope Protein gp120/genetics ; HIV Envelope Protein gp41/genetics ; HIV Infections/*diagnosis/prevention & control ; Humans ; Mass Screening/methods ; Polymerase Chain Reaction/*methods ; Saliva/*virology ; Sensitivity and Specificity ; Workflow ; }, abstract = {Oral fluid (OF) is a highly effective substrate for population-based HIV screening efforts, as it is noninfectious and significantly easier to collect than blood. However, anti-HIV antibodies are found at far lower concentrations in OF compared with blood, leading to poor sensitivity and a longer period of time from infection to detection threshold. Thus, despite its inherent advantages in sample collection, OF is not widely used for population screening. Here we report the development of an HIV OF assay based on Antibody Detection by Agglutination-PCR (ADAP) technology. This assay is 1,000-10,000 times more analytically sensitive than clinical enzyme-linked immunoassays (EIAs), displaying both 100% clinical sensitivity and 100% specificity for detecting HIV antibodies within OF samples. We show that the enhanced analytical sensitivity enables this assay to correctly identify HIV-infected individuals otherwise missed by current OF assays. We envision that the attributes of this improved HIV OF assay can increase testing rates of at-risk individuals while enabling diagnosis and treatment at an earlier time point.}, } @article {pmid29358040, year = {2018}, author = {Mohd Zain, SN and Basáñez, MG}, title = {Collaborate or Collapse: Capacity Building in Zoonotic and Neglected Tropical Disease Modelling.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {356-358}, doi = {10.1016/j.pt.2017.12.009}, pmid = {29358040}, issn = {1471-5007}, mesh = {Animals ; Asia, Southeastern ; *Capacity Building ; Humans ; *Models, Theoretical ; Neglected Diseases/epidemiology ; Tropical Medicine/*trends ; Zoonoses/epidemiology ; }, abstract = {We share the insights from a successful collaboration in organizing and implementing an international scientific capacity-building workshop in Malaysia titled Mathematical Modelling of Neglected Infectious Diseases: Capacity Building in Southeast Asia. This workshop focused on the delivery of technical know-how and on essential soft skills related to effective grant proposal writing and networking.}, } @article {pmid29357945, year = {2018}, author = {Hainz, N and Beckmann, A and Schubert, M and Haase, A and Martin, U and Tschernig, T and Meier, C}, title = {Human stem cells express pannexins.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {54}, pmid = {29357945}, issn = {1756-0500}, mesh = {Cell Line ; Connexins/*genetics ; Endothelial Progenitor Cells/cytology/metabolism ; Fetal Blood/cytology ; *Gene Expression ; Human Embryonic Stem Cells/cytology/metabolism ; Humans ; Induced Pluripotent Stem Cells/cytology/metabolism ; Nerve Tissue Proteins/*genetics ; Reverse Transcriptase Polymerase Chain Reaction ; Stem Cells/cytology/*metabolism ; }, abstract = {OBJECTIVE: Pannexins are channel proteins important for the release of calcium and adenosine triphosphate, which are among other functions involved in early development. Here, the expression of pannexins was investigated in induced pluripotent stem cells derived from human cord blood endothelial cells (hCBiPS2), in hematopoietic stem cell-derived induced pluripotent stem cells (HSC_F1285_T-iPS2) and in human embryonic stem cells (HES-3). The expression of pannexin (Panx) 1-3 mRNAs was analyzed in all three undifferentiated stem cell lines. Stem cells then underwent undirected differentiation into embryoid bodies and were analyzed regarding expression of germ layer-specific genes.

RESULTS: Panx1, Panx2, and Panx3 mRNAs were expressed in all undifferentiated stem cell lines investigated. In comparison, Panx1 showed the highest expression among all pannexins. The undirected differentiation resulted in a mixed germ layer genotype in all three stem cell lines. Whereas the expression of Panx1 was not affected by differentiation, the expression of Panx2 was slightly increased in differentiated hCBiPS2 cells, HSC_F1285_T-iPS2 as well as HES3 cells as compared to their undifferentiated counterparts. A slight increase of Panx3 expression was observed in differentiated hCBiPS2 cells only. In conclusion, pluripotent stem cells express all three pannexin genes.}, } @article {pmid29357944, year = {2018}, author = {Takaya, Y and Matsubayashi, H and Kitaya, K and Nishiyama, R and Yamaguchi, K and Takeuchi, T and Ishikawa, T}, title = {Minimum values for midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {61}, pmid = {29357944}, issn = {1756-0500}, mesh = {Adult ; Coitus ; Estradiol/*blood ; Female ; Humans ; Insemination ; Luteal Phase ; Menotropins/administration & dosage ; Ovulation/drug effects ; Pregnancy ; Pregnancy Outcome ; Progesterone/*blood ; }, abstract = {OBJECTIVE: The aim of the study was to assess the lower limits of midluteal plasma progesterone and estradiol concentrations in patients who achieved pregnancy with timed intercourse or intrauterine insemination without a human menopausal gonadotropin stimulation.

RESULTS: We included 297 pregnant cycles of 297 women and assessed midluteal plasma progesterone and estradiol concentrations and pregnancy outcomes, retrospectively. These cycles were compared with the non-pregnant cycles (406 cycles) of the same women who became pregnant. Mean midluteal plasma P4 and E2 concentrations were significantly (P < 0.01) higher in pregnant cycles (14.5 and 188.5 pg/mL) than in non-pregnant cycles (10.7 and 162.6 pg/mL). The 5 percentiles of progesterone and estradiol in pregnant cycles were 5.6 and 70.2 pg/mL, respectively. The lowest progesterone and estradiol levels in pregnant cycles were 2.3 and 23.4 pg/mL, respectively. In non-pregnant cycles, many women had low P4 levels that were less than 5.6 ng/mL. Subgroup analyses showed slight differences among the four groups, which may have been due to the ovarian function of each group. Miscarriage was not related to progesterone and estradiol concentrations. These values may be useful for the evaluation of necessary values for pregnancy with timed intercourse or intrauterine insemination.}, } @article {pmid29357942, year = {2018}, author = {Pujol, V and Wissuwa, M}, title = {Contrasting development of lysigenous aerenchyma in two rice genotypes under phosphorus deficiency.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {60}, pmid = {29357942}, issn = {1756-0500}, support = {FY2014 JSPS Postdoctoral Fellowship for Foreign Researchers//Japan Society for the Promotion of Science/ ; }, mesh = {Adaptation, Physiological ; Biomass ; Genotype ; Oryza/genetics/growth & development/*metabolism ; Phosphorus/*metabolism ; Plant Roots/genetics/growth & development/*metabolism ; }, abstract = {OBJECTIVES: Phosphorus (P) deficiency is a major limitation to plant growth. Under several abiotic stresses, including P deficiency, upland cereal crops, such as maize, are well known to develop lysigenous aerenchyma, a root tissue containing gas spaces. Contrary to upland species, rice develops aerenchyma constitutively. Nevertheless, aerenchyma in rice is also enhanced by several abiotic stresses, including P deficiency. However, studies are limited and genotypic differences are not clear.

RESULTS: The formation of inducible aerenchyma in response to P deficiency was evaluated in two rice genotypes, DJ123 and Nerica4. Whole root porosity increased for both genotypes in low P conditions, but was more pronounced in DJ123. Direct aerenchyma measurements, at 20 and 30 mm from the seminal root tip, revealed that aerenchyma in low P conditions was only enhanced in DJ123. These results confirm that P deficiency in rice induces the formation of aerenchyma, and further show that genotypic differences exist. Interestingly, DJ123 is considered tolerant to P deficiency, whereas Nerica4 is sensitive, pointing towards a potential role of aerenchyma in tolerance to P deficiency.}, } @article {pmid29357920, year = {2018}, author = {Siraj, N and Issac, J and Anwar, M and Mehari, Y and Russom, S and Kahsay, S and Frezghi, H}, title = {Establishment of hematological reference intervals for healthy adults in Asmara.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {55}, pmid = {29357920}, issn = {1756-0500}, mesh = {Adult ; Cross-Sectional Studies ; Eritrea ; Erythrocyte Count ; Erythrocyte Indices ; Female ; *Health Status ; Hematocrit ; Hematologic Tests/methods/*standards ; Hemoglobins ; Humans ; Leukocyte Count ; Male ; *Reference Values ; }, abstract = {OBJECTIVES: Clinical laboratory reference intervals used in a specific area should be derived from the local population as they are influenced by many factors. The purpose of this quantitative cross sectional study was to establish hematological reference intervals for healthy adults in Asmara and to determine whether the currently used reference interval do represent the adult population in the city. In addition, the established reference intervals were compared to findings from similar studies conducted in selected countries in Africa.

RESULTS: There was a significant difference between males and females in the reference intervals for erythrocyte count, hemoglobin, hematocrit, mean cell volume, mean cell hemoglobin, mean cell hemoglobin concentration and differential white blood cell count. All the evaluated hematological analytes were found to be higher in males than in females except for platelet count. The out of range percentage for the parameters extends from 3.5 to 46.7%; with red blood cell count having the lowest while mean cell volume having the highest out of range percentage. The results indicated that the currently used reference interval does not represent the population in Asmara and are different from those obtained elsewhere in Africa.}, } @article {pmid29357917, year = {2018}, author = {Zemene, T and Shiferaw, MB}, title = {Prevalence of intestinal parasitic infections in children under the age of 5 years attending the Debre Birhan referral hospital, North Shoa, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {58}, pmid = {29357917}, issn = {1756-0500}, mesh = {Animals ; Ascaris lumbricoides/isolation & purification ; Child, Preschool ; Cross-Sectional Studies ; Entamoeba histolytica/isolation & purification ; Ethiopia/epidemiology ; Feces/*parasitology ; Giardia lamblia/isolation & purification ; Hand Disinfection ; Humans ; Hygiene/standards ; Infant ; Infant, Newborn ; Intestinal Diseases, Parasitic/*epidemiology ; Parasites/classification/*isolation & purification ; Prevalence ; *Referral and Consultation ; Trichuris/isolation & purification ; }, abstract = {OBJECTIVE: Intestinal parasitic infection is one of the major childhood health problems in developing countries. In Ethiopia, epidemiological data for several localities is limited. Hence, the aim of this study is to assess intestinal parasitic infections among under-five children attending in Debre Birhan referral hospital, which could help to decrease morbidity and mortality in children. A cross-sectional study was conducted in February, 2014. Stool specimens were collected and examined using concentration method.

RESULTS: Out of the 247 under-five children participated, 17.4% (95% CI 12.7-22.1%) of the children were infected with at least one or more protozoa parasites (14.2% [95% CI 9.9-18.5%]) and helminthes (3.2% [95% CI 1.0-5.4%]). Giardia lamblia (8.5%), Entamoeba histolytica/dispar (5.7%), Trichuris trichiura (1.6%) and Ascaris lumbricoides (1.2%) were the most identified parasites. Parasitic infection was higher in children who had source of drinking water from the river (36.8%), among children from mothers with poor hand washing practice (31.7%), and among children born from illiterate mothers (27.5%). This revealed that intestinal parasites affect the health of under-five children in the setting. Hence, improving environmental hygiene and inadequate water sanitation, and health education for behavioral changes to personal hygiene would be crucial for effective control of the parasite infections.}, } @article {pmid29357913, year = {2018}, author = {Nelwan, EJ and Sinto, R and Subekti, D and Adiwinata, R and Waslia, L and Loho, T and Safari, D and Widodo, D}, title = {Screening of methicillin-resistant Staphylococcus aureus nasal colonization among elective surgery patients in referral hospital in Indonesia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {56}, pmid = {29357913}, issn = {1756-0500}, support = {Operational Research 2015//Cipto Mangunkusumo Hospital/ ; }, mesh = {Adult ; Cross-Sectional Studies ; Elective Surgical Procedures/*methods ; Female ; Humans ; Indonesia/epidemiology ; Male ; Methicillin-Resistant Staphylococcus aureus/genetics/*isolation & purification ; Middle Aged ; Nose/*microbiology ; Preoperative Period ; Prevalence ; *Referral and Consultation ; Staphylococcal Infections/epidemiology/*microbiology ; Staphylococcus aureus/genetics/isolation & purification ; }, abstract = {OBJECTIVE: Methicillin-resistant Staphylococcus aureus (MRSA) colonization is associated with serious surgical site infection in high-risk patients. High prevalence of MRSA colonization was reported in many settings, nonetheless local data is required. The purpose of this study is to identify the prevalence and risk factor of MRSA nasal carriage in adult patients in National Referral Hospital in Indonesia before underwent elective surgical procedure.

RESULTS: From 384 patients, 16.9% patients of them had undergone orthopaedic surgery, 51.3% had received antibiotics within the previous 3-month and 41.1% patients had history of hospitalization within the previous 1 year. Total of 21.6% patients were on invasive devices for at least 48 h before the operation; 24.2% had an open wound; 19.3% patients were referred from other hospital/ward. Of these patients, solid tumor without metastasis was the most common factor identified by the Charlson index (38.3%). Nasal colonization of Gram-positive bacteria was detected in 76.8%; S. aureus in 15.6% of patients (n = 60). MRSA was identified in three isolates (0.8%) by both culture and polymerase chain reaction (PCR) tests. Due to low prevalence of MRSA nasal carriage, this finding supports the recommendation to not routinely apply mupirocin for nasal decolonization on patient planned for surgery in Indonesia.}, } @article {pmid29357907, year = {2018}, author = {Lix, LM and Leslie, WD and Majumdar, SR}, title = {Measuring improvement in fracture risk prediction for a new risk factor: a simulation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {62}, pmid = {29357907}, issn = {1756-0500}, mesh = {Aged ; *Bone Density ; Cohort Studies ; Computer Simulation ; Female ; Humans ; Manitoba/epidemiology ; Middle Aged ; Models, Theoretical ; Osteoporotic Fractures/epidemiology/*metabolism ; Prevalence ; Registries/*statistics & numerical data ; Risk Assessment/methods/*statistics & numerical data ; Risk Factors ; }, abstract = {OBJECTIVE: Improvements in clinical risk prediction models for osteoporosis-related fracture can be evaluated using area under the receiver operating characteristic (AUROC) curve and calibration, as well as reclassification statistics such as the net reclassification improvement (NRI) and integrated discrimination improvement (IDI) statistics. Our objective was to compare the performance of these measures for assessing improvements to an existing fracture risk prediction model. We simulated the effect of a new, randomly-generated risk factor on prediction of major osteoporotic fracture (MOF) for the internationally-validated FRAX® model in a cohort from the Manitoba Bone Mineral Density (BMD) Registry.

RESULTS: The study cohort was comprised of 31,999 women 50+ years of age; 9.9% sustained at least one MOF in a mean follow-up of 8.4 years. The original prediction model had good discriminative performance, with AUROC = 0.706 and calibration (ratio of observed to predicted risk) of 0.990. The addition of the simulated risk factor resulted in improvements in NRI and IDI for most investigated conditions, while AUROC decreased and changes in calibration were negative. Reclassification measures may give different information than discrimination and calibration about the performance of new clinical risk factors.}, } @article {pmid29357904, year = {2018}, author = {Kaleem, T and Miller, D and Waddle, MR and Yanez, M and Gianforti, B and Buskirk, S}, title = {Implementation of patient pagers in radiation oncology waiting rooms for patient privacy and satisfaction.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {59}, pmid = {29357904}, issn = {1756-0500}, mesh = {Female ; *Hospital Communication Systems ; Hospital Departments ; Humans ; Male ; Middle Aged ; *Patient Satisfaction ; Patients/*psychology/statistics & numerical data ; *Privacy ; Prospective Studies ; *Radiation Oncology ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: In order to improve privacy, quality, and coordination of care, a patient pager system was introduced to notify patients of daily treatment in the Department of Radiation Oncology. One hundred patients undergoing daily radiation therapy prospectively participated in a six-question survey addressing the paging service, privacy prior to pager use, and demographics. Twelve radiation therapists also participated in a survey addressing privacy and workflow.

RESULTS: Survey results from all patient participants revealed that convenience, privacy, ease of use, desire for use for consults and return visits were highly rated as very good to excellent. The top three categories were "ease of use," "convenience" and "privacy." Nineteen patients had the experience of our waiting room prior to introduction of the patient pagers and highly rated "privacy," "efficiency," and "satisfaction." Twelve radiation therapists participated and rated workflow related categories fair to good. Only patient privacy was rated as very good to excellent. Thus, patients and staff highly rated the paging system for privacy protection and satisfaction. However, it did not change overall workflow. Our study shows clinics should prioritize privacy in the waiting room to address the emotional needs of patients and improve satisfaction.}, } @article {pmid29357899, year = {2018}, author = {Jouego, CG and Agbor, VN and Noeske, J and Manuel, NA and Ayuk, LN}, title = {Pediatric multi-drug resistant-tuberculosis and HIV co-infection in a resource-limited setting: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {57}, pmid = {29357899}, issn = {1756-0500}, mesh = {Cameroon ; Child ; *Coinfection ; HIV Infections/*virology ; Health Resources/*supply & distribution ; Humans ; Male ; Mycobacterium tuberculosis/isolation & purification ; Sputum/microbiology ; Tuberculosis, Multidrug-Resistant/*microbiology ; }, abstract = {BACKGROUND: Tuberculosis remains a major cause of morbidity and mortality worldwide, especially in developing countries. The diagnosis and treatment of multi-drug resistant tuberculosis (MDR-TB) in children remain a major limitation in this setting, largely due to difficulties in isolating Mycobacterium tuberculosis from pediatric specimens, management with toxic second line drugs, and practically the inexistence of contact tracing. In 2016, the World Health Organization (WHO) recommended a standardized 9-month regimen for adults and children in zones which are highly endemic for the human immunodeficiency virus (HIV). Herein, we present a case of pediatric MDR-TB/HIV co-infection highlighting the difficulties in treatment and the importance of contact tracing.

CASE PRESENTATION: A 6-year old male infant from the West Region of Cameroon infected with HIV who presented at a local health center with a 10 days history of productive cough associated with nocturnal fever and abdominal pains non responsive to broad spectrum antibiotics. A sputum sample analysis requested was smear positive for acid-fast bacilli, and he was initiated on quadritherapy for drug sensitive pulmonary tuberculosis. Since he was a household contact of the mother who was being managed in a referral hospital for MDR-TB at 1 month of treatment, and given his critical clinical situation, a gastric aspirate was repeated and sent for Xpert MTB/RIF to the Tuberculosis Reference Laboratory which was positive for a Rifampicin resistant strain of M. tuberculosis. The short 9 months regimen against MDR-TB was then initiated. During the course of his management, he developed minor side effects of the drugs which were managed symptomatically.

CONCLUSION: Even though pediatric MDR-TB is difficult to confirm, it can be treated with favorable clinical outcomes using the short regimen recommended by the WHO. Experts involved in the control of tuberculosis over the national territory should consider adopting routine contact tracing for all cases of tuberculosis particularly amongst children.}, } @article {pmid29357852, year = {2018}, author = {Leibovich, A and Kot-Leibovich, H and Ben-Zvi, D and Fainsod, A}, title = {ADMP controls the size of Spemann's organizer through a network of self-regulating expansion-restriction signals.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {13}, pmid = {29357852}, issn = {1741-7007}, abstract = {BACKGROUND: The bone morphogenetic protein (BMP) signaling gradient is central for dorsoventral patterning in amphibian embryos. This gradient is established through the interaction of several BMPs and BMP antagonists and modulators, some secreted by Spemann's organizer, a cluster of cells coordinating embryonic development. Anti-dorsalizing morphogenetic protein (ADMP), a BMP-like transforming growth factor beta ligand, negatively affects the formation of the organizer, although it is robustly expressed within the organizer itself. Previously, we proposed that this apparent discrepancy may be important for the ability of ADMP to scale the BMP gradient with embryo size, but how this is achieved is unclear.

RESULTS: Here we report that ADMP acts in the establishment of the organizer via temporally and mechanistically distinct signals. At the onset of gastrulation, ADMP is required to establish normal organizer-specific gene expression domains, thus displaying a dorsal, organizer-promoting function. The organizer-restricting, BMP-like function of ADMP becomes apparent slightly later, from mid-gastrula. The organizer-promoting signal of ADMP is mediated by the activin A type I receptor, ACVR1 (also known as activin receptor-like kinase-2, ALK2). ALK2 is expressed in the organizer and is required for organizer establishment. The anti-organizer function of ADMP is mediated by ACVRL1 (ALK1), a putative ADMP receptor expressed in the lateral regions flanking the organizer that blocks expansion of the organizer. Truncated ALK1 prevents the organizer-restricting effects of ADMP overexpression, suggesting a ligand-receptor interaction. We also present a mathematical model of the regulatory network controlling the size of the organizer.

CONCLUSIONS: We show that the opposed, organizer-promoting and organizer-restricting roles of ADMP are mediated by different receptors. A self-regulating network is proposed in which ADMP functions early through ALK2 to expand its own expression domain, the organizer, and later functions through ALK1 to restrict this domain. These effects are dependent on ADMP concentration, timing, and the spatial localization of the two receptors. This self-regulating temporal switch may control the size of the organizer and the genes expressed within in response to genetic and external stimuli during gastrulation.}, } @article {pmid29357837, year = {2018}, author = {Maulik, U and Sen, S and Mallik, S and Bandyopadhyay, S}, title = {Detecting TF-miRNA-gene network based modules for 5hmC and 5mC brain samples: a intra- and inter-species case-study between human and rhesus.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {9}, pmid = {29357837}, issn = {1471-2156}, mesh = {5-Methylcytosine/*analogs & derivatives/*analysis ; Animals ; Brain/*metabolism ; *DNA Methylation ; *Gene Regulatory Networks ; Humans ; Macaca mulatta/*genetics ; Species Specificity ; }, abstract = {BACKGROUND: Study of epigenetics is currently a high-impact research topic. Multi stage methylation is also an area of high-dimensional prospect. In this article, we provide a new study (intra and inter-species study) on brain tissue between human and rhesus on two methylation cytosine variants based data-profiles (viz., 5-hydroxymethylcytosine (5hmC) and 5-methylcytosine (5mC) samples) through TF-miRNA-gene network based module detection.

RESULTS: First of all, we determine differentially 5hmC methylated genes for human as well as rhesus for intra-species analysis, and differentially multi-stage methylated genes for inter-species analysis. Thereafter, we utilize weighted topological overlap matrix (TOM) measure and average linkage clustering consecutively on these genesets for intra- and inter-species study.We identify co-methylated and multi-stage co-methylated gene modules by using dynamic tree cut, for intra-and inter-species cases, respectively. Each module is represented by individual color in the dendrogram. Gene Ontology and KEGG pathway based analysis are then performed to identify biological functionalities of the identified modules. Finally, top ten regulator TFs and targeter miRNAs that are associated with the maximum number of gene modules, are determined for both intra-and inter-species analysis.

CONCLUSIONS: The novel TFs and miRNAs obtained from the analysis are: MYST3 and ZNF771 as TFs (for human intra-species analysis), BAZ2B, RCOR3 and ATF1 as TFs (for rhesus intra-species analysis), and mml-miR-768-3p and mml-miR-561 as miRs (for rhesus intra-species analysis); and MYST3 and ZNF771 as miRs(for inter-species study). Furthermore, the genes/TFs/miRNAs that are already found to be liable for several brain-related dreadful diseases as well as rare neglected diseases (e.g., wolf Hirschhorn syndrome, Joubarts Syndrome, Huntington's disease, Simian Immunodeficiency Virus(SIV) mediated enchaphilits, Parkinsons Disease, Bipolar disorder and Schizophenia etc.) are mentioned.}, } @article {pmid29357834, year = {2018}, author = {Rochus, CM and Tortereau, F and Plisson-Petit, F and Restoux, G and Moreno-Romieux, C and Tosser-Klopp, G and Servin, B}, title = {Revealing the selection history of adaptive loci using genome-wide scans for selection: an example from domestic sheep.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {71}, pmid = {29357834}, issn = {1471-2164}, support = {ANR-11-INBS-0003//Agence Nationale de la Recherche/International ; }, mesh = {Alleles ; Animals ; *Evolution, Molecular ; Genetic Loci ; Genomics ; Genotyping Techniques ; Haplotypes ; *Mutation ; Polymorphism, Single Nucleotide ; *Selection, Genetic ; Sheep, Domestic/*genetics ; }, abstract = {BACKGROUND: One of the approaches to detect genetics variants affecting fitness traits is to identify their surrounding genomic signatures of past selection. With established methods for detecting selection signatures and the current and future availability of large datasets, such studies should have the power to not only detect these signatures but also to infer their selective histories. Domesticated animals offer a powerful model for these approaches as they adapted rapidly to environmental and human-mediated constraints in a relatively short time. We investigated this question by studying a large dataset of 542 individuals from 27 domestic sheep populations raised in France, genotyped for more than 500,000 SNPs.

RESULTS: Population structure analysis revealed that this set of populations harbour a large part of European sheep diversity in a small geographical area, offering a powerful model for the study of adaptation. Identification of extreme SNP and haplotype frequency differences between populations listed 126 genomic regions likely affected by selection. These signatures revealed selection at loci commonly identified as selection targets in many species ("selection hotspots") including ABCG2, LCORL/NCAPG, MSTN, and coat colour genes such as ASIP, MC1R, MITF, and TYRP1. For one of these regions (ABCG2, LCORL/NCAPG), we could propose a historical scenario leading to the introgression of an adaptive allele into a new genetic background. Among selection signatures, we found clear evidence for parallel selection events in different genetic backgrounds, most likely for different mutations. We confirmed this allelic heterogeneity in one case by resequencing the MC1R gene in three black-faced breeds.

CONCLUSIONS: Our study illustrates how dense genetic data in multiple populations allows the deciphering of evolutionary history of populations and of their adaptive mutations.}, } @article {pmid29357833, year = {2018}, author = {Gerring, ZF and McRae, AF and Montgomery, GW and Nyholt, DR}, title = {Genome-wide DNA methylation profiling in whole blood reveals epigenetic signatures associated with migraine.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {69}, pmid = {29357833}, issn = {1471-2164}, support = {APP1046880//National Health and Medical Research Council/International ; APP1075175//National Health and Medical Research Council/International ; APP1083405//National Health and Medical Research Council/International ; 602633//EUROHEADPAIN/International ; }, mesh = {Adolescent ; Adult ; Aged ; Case-Control Studies ; Child ; *DNA Methylation ; *Epigenomics ; Female ; *Genetic Markers ; *Genome, Human ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Migraine Disorders/blood/*diagnosis/*genetics ; Polymorphism, Single Nucleotide ; Regulatory Sequences, Nucleic Acid ; Young Adult ; }, abstract = {BACKGROUND: Migraine is a common heritable neurovascular disorder typically characterised by episodic attacks of severe pulsating headache and nausea, often accompanied by visual, auditory or other sensory symptoms. Although genome-wide association studies have identified over 40 single nucleotide polymorphisms associated with migraine, there remains uncertainty about the casual genes involved in disease pathogenesis and how their function is regulated.

RESULTS: We performed an epigenome-wide association study, quantifying genome-wide patterns of DNA methylation in 67 migraine cases and 67 controls with a matching age and sex distribution. Association analyses between migraine and methylation probe expression, after adjustment for cell type proportions, indicated an excess of small P values, but there was no significant single-probe association after correction for multiple testing (P < 1.09 × 10- 7). However, utilising a 1 kb sliding window approach to combine adjacent migraine-methylation association P values, we identified 62 independent differentially methylated regions (DMRs) underlying migraine (false discovery rate < 0.05). Migraine association signals were subtle but consistent in effect direction across the length of each DMR. Subsequent analyses showed that the migraine-associated DMRs were enriched in regulatory elements of the genome and were in close proximity to genes involved in solute transportation and haemostasis.

CONCLUSIONS: This study represents the first genome-wide analysis of DNA methylation in migraine. We have identified DNA methylation in the whole blood of subjects associated with migraine, highlighting novel loci that provide insight into the biological pathways and mechanisms underlying migraine pathogenesis.}, } @article {pmid29357832, year = {2018}, author = {Liu, S and Feuerstein, U and Luesink, W and Schulze, S and Asp, T and Studer, B and Becker, HC and Dehmer, KJ}, title = {DArT, SNP, and SSR analyses of genetic diversity in Lolium perenne L. using bulk sampling.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {10}, pmid = {29357832}, issn = {1471-2156}, mesh = {Breeding ; *Genetic Variation ; Hybrid Vigor ; Lolium/classification/*genetics/physiology ; Microsatellite Repeats ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Lolium perenne L. is the most important forage grass species in temperate regions. It is also considered as a sustainable source of biomass for energy production. However, improvement in biomass yield has been limited by comparison with other major crops. More efficient utilisation of genetic resources and improved breeding schemes are required to advance L. perenne breeding. In an attempt to elucidate the extent of genetic diversity in L. perenne, 1384 DArT, 182 SNP and 48 SSR markers were applied to 297 accessions (Set I) contributed by three German breeding companies and the IPK Genebank. Due to the heterogeneous nature of Lolium accessions, bulk samples were used. Apart from germplasm set I, additional set II and set III was used to determine the reproducibility of marker system and judge the feasibility of bulk strategy in this study.

RESULTS: By assessing different bulk sizes, 24 individuals per sample were shown to be a representative number of plants to discriminate different accessions. Among the 297 accessions, all marker types revealed a high polymorphism rate; 1.99, 2.00 and 8.19 alleles, were obtained per locus on average using DArTs, SNPs and SSRs, respectively. The Jaccard distance for DArT markers ranged from 0.00 to 0.73, the Modified Roger's distance (MRD) for SNP markers ranged from 0.03 to 0.52, and for SSR markers from 0.26 to 0.76. Gene diversity for dominant DArT and co-dominant SNP and SSR markers was found to be 0.26, 0.32 and 0.45, respectively. DArT markers showed the highest consistency and reproducibility.

CONCLUSION: The resulting data were evaluated using a number of different classification methods, but none of the methods showed a clear differentiation into distinct genetic pools. With regard to hybrid breeding, this will possibly impede substantial progress towards increased biomass yields of L. perenne by utilising heterosis.}, } @article {pmid29357827, year = {2018}, author = {Xu, Y and Huang, B}, title = {Transcriptomic analysis reveals unique molecular factors for lipid hydrolysis, secondary cell-walls and oxidative protection associated with thermotolerance in perennial grass.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {70}, pmid = {29357827}, issn = {1471-2164}, mesh = {Adaptation, Physiological ; Cell Wall/*genetics ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Heat-Shock Response ; High-Throughput Nucleotide Sequencing ; Hydrolysis ; Lipids/*genetics/physiology ; *Oxidative Stress ; Plant Proteins/*genetics ; Poaceae/*genetics/physiology ; *Thermotolerance ; }, abstract = {BACKGROUND: Heat stress is the primary abiotic stress limiting growth of cool-season grass species. The objective of this study was to determine molecular factors and metabolic pathways associated with superior heat tolerance in thermal bentgrass (Agrostis scabra) by comparative analysis of transcriptomic profiles with its co-generic heat-sensitive species creeping bentgrass (A. stolonifera).

RESULTS: Transcriptomic profiling by RNA-seq in both heat-sensitive A. stolonifera (cv. 'Penncross') and heat-tolerant A. scabra exposed to heat stress found 1393 (675 up- and 718 down-regulated) and 1508 (777 up- and 731 down-regulated) differentially-expressed genes, respectively. The superior heat tolerance in A. scabra was associated with more up-regulation of genes in oxidative protection, proline biosynthesis, lipid hydrolysis, hemicellulose and lignin biosynthesis, compared to heat-sensitive A. stolonifera. Several transcriptional factors (TFs), such as high mobility group B protein 7 (HMGB7), dehydration-responsive element-binding factor 1a (DREB1a), multiprotein-bridging factor 1c (MBF1c), CCCH-domain containing protein 47 (CCCH47), were also found to be up-regulated in A. scabra under heat stress.

CONCLUSIONS: The unique TFs and genes identified in thermal A. scabra could be potential candidate genes for genetic modification of cultivated grass species for improving heat tolerance, and the associated pathways could contribute to the transcriptional regulation for superior heat tolerance in bentgrass species.}, } @article {pmid29357825, year = {2018}, author = {Xu, Z and Ge, Y and Zhang, W and Zhao, Y and Yang, G}, title = {The walnut JrVHAG1 gene is involved in cadmium stress response through ABA-signal pathway and MYB transcription regulation.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {19}, pmid = {29357825}, issn = {1471-2229}, support = {XKL201731//Forestry Science and Technology Project of Hunan Province/International ; 2016TP2007/2016TP1014//Science and Technology Project of Hunan Province/International ; 2017T100782//Special Financial Grant from the China Postdoctoral Science Foundation/International ; 2016BSHEDZZ117//Postdoctoral Science Foundation Project of Shaanxi Province/International ; }, mesh = {Abscisic Acid/metabolism ; Arabidopsis/*genetics/metabolism ; Cadmium/adverse effects ; Cadmium Chloride/*adverse effects ; *Gene Expression Regulation, Plant ; Juglans/genetics/*physiology ; Plant Leaves/metabolism ; Plant Proteins/*genetics/metabolism ; Plant Roots/metabolism ; Plants, Genetically Modified/genetics/metabolism ; Signal Transduction ; Trans-Activators/genetics/metabolism ; Vacuolar Proton-Translocating ATPases/*genetics/metabolism ; }, abstract = {BACKGROUND: Vacuolar H+-ATPase (V-ATPase) is a vital protein complex involved in abiotic stress response in plants. The G subunit of Juglans regia (JrVHAG1) was previously identified as a drought tolerance-related gene involved in the ABA (abscisic acid)-signal pathway. Heavy metal stress is becoming a major detriment for plant growth, development, and production. In order to understand the role of JrVHAG1, the potential function mechanism of JrVHAG1 exposed to CdCl2 stress was confirmed in this study.

RESULTS: Transcription of JrVHAG1 was induced by ABA and increased to 58.89-fold (roots) and 7.38-fold (leaves) and by CdCl2 to 2.65- (roots) and 11.42-fold (leaves) relative to control, respectively. Moreover, when treated simultaneously with ABA and CdCl2 (ABA+CdCl2), JrVHAG1 was up-regulated to 110.13- as well as 165.42-fold relative to control in the roots and leaves, accordingly. Compared to the wild type (WT) Arabidopsis plants, the transgenic plants with overexpression of JrVHAG1 (G2, G6, and G9) exhibited increased seed germination rate, biomass accumulation, proline content, and activities of superoxide dismutase (SOD) and peroxidase (POD) under ABA, CdCl2, and ABA+CdCl2 treatments. In contrast, the reactive oxygen species (ROS) staining, malondialdehyde (MDA) content, hydrogen dioxide (H2O2) content, as well as electrolyte leakage (EL) rates of transgenic seedlings were all lower than those of WT exposed to ABA, CdCl2 and ABA+CdCl2 stresses. Furthermore, a 1200 bp promoter fragment of JrVHAG1 was isolated by analyzing the genome of J. regia, in which the cis-elements were identified. This JrVHAG1 promoter fragment showed expression activity that was enhanced significantly when subjected to the above treatments. Yeast one-hybrid assay and transient expression analysis demonstrated that JrMYB2 specifically bound to the MYBCORE motif and shared similar expression patterns with JrVHAG1 under ABA, CdCl2 and ABA+CdCl2 stress conditions.

CONCLUSIONS: Our results suggested that the JrVHAG1 gene functions as a CdCl2 stress response regulator by participating in ABA-signal pathway and MYB transcription regulation network. JrVHAG1 gene is a useful candidate gene for heavy metal stress tolerance in plant molecular breeding.}, } @article {pmid29357822, year = {2018}, author = {Chen, S and Huang, T and Wen, T and Li, H and Xu, M and Gu, J}, title = {MutScan: fast detection and visualization of target mutations by scanning FASTQ data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {16}, pmid = {29357822}, issn = {1471-2105}, support = {61472411//National Natural Science Foundation of China/International ; 2015AA043203//The national 863 Program of China/International ; KC2015JSJS0028A//Technology Development and Creative Design Program of Nanshan Shenzhen/International ; JSGG20160229123927512//Special Funds for Future Industries of Shenzhen/International ; CYZZ20150527145115656//SZSTI Entrepreneurship Funds of Shenzhen/International ; }, mesh = {*Algorithms ; Circulating Tumor DNA/chemistry/genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Neoplasms/genetics/pathology ; *Search Engine ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Some types of clinical genetic tests, such as cancer testing using circulating tumor DNA (ctDNA), require sensitive detection of known target mutations. However, conventional next-generation sequencing (NGS) data analysis pipelines typically involve different steps of filtering, which may cause miss-detection of key mutations with low frequencies. Variant validation is also indicated for key mutations detected by bioinformatics pipelines. Typically, this process can be executed using alignment visualization tools such as IGV or GenomeBrowse. However, these tools are too heavy and therefore unsuitable for validating mutations in ultra-deep sequencing data.

RESULT: We developed MutScan to address problems of sensitive detection and efficient validation for target mutations. MutScan involves highly optimized string-searching algorithms, which can scan input FASTQ files to grab all reads that support target mutations. The collected supporting reads for each target mutation will be piled up and visualized using web technologies such as HTML and JavaScript. Algorithms such as rolling hash and bloom filter are applied to accelerate scanning and make MutScan applicable to detect or visualize target mutations in a very fast way.

CONCLUSION: MutScan is a tool for the detection and visualization of target mutations by only scanning FASTQ raw data directly. Compared to conventional pipelines, this offers a very high performance, executing about 20 times faster, and offering maximal sensitivity since it can grab mutations with even one single supporting read. MutScan visualizes detected mutations by generating interactive pile-ups using web technologies. These can serve to validate target mutations, thus avoiding false positives. Furthermore, MutScan can visualize all mutation records in a VCF file to HTML pages for cloud-friendly VCF validation. MutScan is an open source tool available at GitHub: https://github.com/OpenGene/MutScan.}, } @article {pmid29357817, year = {2018}, author = {Tsagris, M and Lagani, V and Tsamardinos, I}, title = {Feature selection for high-dimensional temporal data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {17}, pmid = {29357817}, issn = {1471-2105}, support = {617393//European Research Council/International ; }, mesh = {*Algorithms ; Genomics ; Linear Models ; }, abstract = {BACKGROUND: Feature selection is commonly employed for identifying collectively-predictive biomarkers and biosignatures; it facilitates the construction of small statistical models that are easier to verify, visualize, and comprehend while providing insight to the human expert. In this work we extend established constrained-based, feature-selection methods to high-dimensional "omics" temporal data, where the number of measurements is orders of magnitude larger than the sample size. The extension required the development of conditional independence tests for temporal and/or static variables conditioned on a set of temporal variables.

RESULTS: The algorithm is able to return multiple, equivalent solution subsets of variables, scale to tens of thousands of features, and outperform or be on par with existing methods depending on the analysis task specifics.

CONCLUSIONS: The use of this algorithm is suggested for variable selection with high-dimensional temporal data.}, } @article {pmid29357813, year = {2018}, author = {Zurn, JD and Rouse, MN and Chao, S and Aoun, M and Macharia, G and Hiebert, CW and Pretorius, ZA and Bonman, JM and Acevedo, M}, title = {Dissection of the multigenic wheat stem rust resistance present in the Montenegrin spring wheat accession PI 362698.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {67}, pmid = {29357813}, issn = {1471-2164}, support = {2050-21000-029-00D//USDA-ARS National Plant Disease Recovery System/International ; }, mesh = {Basidiomycota/*pathogenicity ; Chromosome Mapping ; Chromosomes, Plant ; *Disease Resistance ; Plant Diseases/*genetics/microbiology ; Plant Proteins/*genetics ; Plant Stems/*genetics/microbiology ; Polymorphism, Single Nucleotide ; *Quantitative Trait Loci ; Seasons ; Triticum/*genetics/microbiology ; }, abstract = {BACKGROUND: Research to identify and characterize stem rust resistance genes in common wheat, Triticum aestivum, has been stimulated by the emergence of Ug99-lineage races of the wheat stem rust pathogen, Puccinia graminis f. sp. tritici (Pgt), in Eastern Africa. The Montenegrin spring wheat landrace PI 362698 was identified as a source of Pgt resistance. This accession exhibits resistance to multiple Ug99-lineage and North American Pgt races at seedling and adult-plant stages. A recombinant inbred population was developed by crossing the susceptible line LMPG-6 with a single plant selection of PI 362698. A genetic map was constructed using the Illumina iSelect 90 K wheat assay and the markers csLv34, NB-LRR3, and wMAS000003 and quantitative trait locus (QTL) analysis was performed.

RESULTS: QTL analysis identified five significant QTLs (α = 0.05) on chromosomes 2B, 3B, 6A, 6D, and 7A associated with wheat stem rust resistance. The QTL on chromosome 3B was identified using both field data from Kenya (Pgt Ug99-lineage races) and seedling data from Pgt race MCCF. This QTL potentially corresponds to Sr12 or a new allele of Sr12. The multi-pathogen resistance gene Sr57 located on chromosome 7D is present in PI 362698 according to the diagnostic markers csLv34 and wMAS000003, however a significant QTL was not detected at this locus. The QTLs on chromosomes 2B, 6A, and 6D were identified during seedling trials and are thought to correspond to Sr16, Sr8a, and Sr5, respectively. The QTL identified on chromosome 7A was detected using MCCF seedling data and may be Sr15 or a potentially novel allele of recently detected Ug99 resistance QTLs.

CONCLUSIONS: The combination of resistance QTLs found in PI 362698 is like the resistance gene combination present in the broadly resistant cultivar Thatcher. As such, PI 362698 may not be a landrace as previously thought. PI 362698 has been crossed with North Dakota wheat germplasm for future breeding efforts. Additional work is needed to fully understand why the combination of genes present in PI 362698 and 'Thatcher' provide such durable resistance.}, } @article {pmid29357812, year = {2018}, author = {Xie, W and Yang, X and Chen, C and Yang, Z and Guo, L and Wang, D and Huang, J and Zhang, H and Wen, Y and Zhao, J and Wu, Q and Wang, S and Coates, BS and Zhou, X and Zhang, Y}, title = {The invasive MED/Q Bemisia tabaci genome: a tale of gene loss and gene gain.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {68}, pmid = {29357812}, issn = {1471-2164}, mesh = {Animals ; Crops, Agricultural/parasitology ; Cytochrome P-450 Enzyme System/genetics ; *Genome, Insect ; Glucuronosyltransferase/genetics ; Hemiptera/*classification/*genetics ; Host Specificity ; Insect Proteins/*genetics ; *Insecticide Resistance ; Multigene Family ; Phylogeny ; Symbiosis ; Transcriptome ; }, abstract = {BACKGROUND: Sweetpotato whitefly, Bemisia tabaci MED/Q and MEAM1/B, are two economically important invasive species that cause considerable damages to agriculture crops through direct feeding and indirect vectoring of plant pathogens. Recently, a draft genome of B. tabaci MED/Q has been assembled. In this study, we focus on the genomic comparison between MED/Q and MEAM1/B, with a special interest in MED/Q's genomic signatures that may contribute to the highly invasive nature of this emerging insect pest.

RESULTS: The genomes of both species share similarity in syntenic blocks, but have significant divergence in the gene coding sequence. Expansion of cytochrome P450 monooxygenases and UDP glycosyltransferases in MED/Q and MEAM1/B genome is functionally validated for mediating insecticide resistance in MED/Q using in vivo RNAi. The amino acid biosynthesis pathways in MED/Q genome are partitioned among the host and endosymbiont genomes in a manner distinct from other hemipterans. Evidence of horizontal gene transfer to the host genome may explain their obligate relationship. Putative loss-of-function in the immune deficiency-signaling pathway due to the gene loss is a shared ancestral trait among hemipteran insects.

CONCLUSIONS: The expansion of detoxification genes families, such as P450s, may contribute to the development of insecticide resistance traits and a broad host range in MED/Q and MEAM1/B, and facilitate species' invasions into intensively managed cropping systems. Numerical and compositional changes in multiple gene families (gene loss and gene gain) in the MED/Q genome sets a foundation for future hypothesis testing that will advance our understanding of adaptation, viral transmission, symbiosis, and plant-insect-pathogen tritrophic interactions.}, } @article {pmid29356878, year = {2018}, author = {Zhang, Y and Chen, P and Ye, G and Lin, H and Ren, D and Guo, L and Zhu, B and Wang, Z}, title = {Complete Genome Sequence of Pseudomonas Parafulva PRS09-11288, a Biocontrol Strain Produces the Antibiotic Phenazine-1-carboxylic Acid.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-018-1441-0}, pmid = {29356878}, issn = {1432-0991}, support = {31521064//National Natural Science Fund of China/ ; }, abstract = {Rhizoctonia solani is a plant pathogenic fungus, which can infect a wide range of economic crops including rice. In this case, biological control of this pathogen is one of the fundmental way to effectively control this pathogen. The Pseudomonas parafulva strain PRS09-11288 was isolated from rice rhizosphere and shows biocontrol ability against R. solani. Here, we analyzed the P. parafulva genome, which is ~ 4.7 Mb, with 4310 coding sequences, 76 tRNAs, and 7 rRNAs. Genome analysis identified a phenazine biosynthetic pathway, which can produce antibiotic phenazine-1-carboxylic acid (PCA). This compound is responsible for biocontrol ability against R. solani Kühn, which is one of the most serious fungus disease on rice. Analysis of the phenazine biosynthesis gene mutant, ΔphzF, which is very important in this pathway, confirmed the relationship between the pathway and PCA production using LC-MS profiles. The annotated full genome sequence of this strain sheds light on the role of P. parafulva PRS09-11288 as a biocontrol bacterium.}, } @article {pmid29356877, year = {2018}, author = {Karim, S and Souho, T and Benlemlih, M and Bennani, B}, title = {Cervical Cancer Induction Enhancement Potential of Chlamydia Trachomatis: A Systematic Review.}, journal = {Current microbiology}, volume = {75}, number = {12}, pages = {1667-1674}, pmid = {29356877}, issn = {1432-0991}, mesh = {Chlamydia Infections/*complications ; Chlamydia trachomatis/*pathogenicity ; Coinfection/microbiology/virology ; Female ; Humans ; Papillomavirus Infections/complications ; Uterine Cervical Neoplasms/*etiology/*microbiology/virology ; }, abstract = {Human papillomavirus (HPV) persistent infection is the necessary but not sufficient cause of cervical cancer. Other co-factors are required to induce cell transformation that will evolve to malignant cervical cancer. These co-factors include physical elements, other sexually transmitted infections, and immune response. Chlamydia trachomatis the most common bacterial sexually transmitted infection is often asymptomatic but causes various syndromes such as cervicitis, endometritis, pelvic inflammatory disease, and infertility. It is established that this bacterium is involved in cell proliferation process and inhibit apoptosis. Furthermore, C. trachomatis may induce chronic inflammation, interfere with immune response by decreasing the number of antigen presenting cells, and reduce the cell-mediated immunity allowing the persistence of HPV. However, it is unclear whether this bacterium plays a particular role in cervical cancer induction. We therefore aimed at enlightening the actual knowledge about the relationship between C. trachomatis and cervical cancer or precursor lesions through a systematic literature review. We summarized and analyzed the epidemiological data on C. trachomatis and its co-infection with HPV and their association to cervical cancer.}, } @article {pmid29356848, year = {2018}, author = {Hoegler, KJ and Hecht, MH}, title = {Artificial Gene Amplification in Escherichia coli Reveals Numerous Determinants for Resistance to Metal Toxicity.}, journal = {Journal of molecular evolution}, volume = {86}, number = {2}, pages = {103-110}, pmid = {29356848}, issn = {1432-1432}, support = {T32 GM007388/GM/NIGMS NIH HHS/United States ; MCB-1409402//Division of Molecular and Cellular Biosciences/ ; }, abstract = {When organisms are subjected to environmental challenges, including growth inhibitors and toxins, evolution often selects for the duplication of endogenous genes, whose overexpression can provide a selective advantage. Such events occur both in natural environments and in clinical settings. Microbial cells-with their large populations and short generation times-frequently evolve resistance to a range of antimicrobials. While microbial resistance to antibiotic drugs is well documented, less attention has been given to the genetic elements responsible for resistance to metal toxicity. To assess which overexpressed genes can endow gram-negative bacteria with resistance to metal toxicity, we transformed a collection of plasmids overexpressing all E. coli open reading frames (ORFs) into naive cells, and selected for survival in toxic concentrations of six transition metals: Cd, Co, Cu, Ni, Ag, Zn. These selections identified 48 hits. In each of these hits, the overexpression of an endogenous E. coli gene provided a selective advantage in the presence of at least one of the toxic metals. Surprisingly, the majority of these cases (28/48) were not previously known to function in metal resistance or homeostasis. These findings highlight the diverse mechanisms that biological systems can deploy to adapt to environments containing toxic concentrations of metals.}, } @article {pmid29356358, year = {2018}, author = {Laubach, ZM and Perng, W and Dolinoy, DC and Faulk, CD and Holekamp, KE and Getty, T}, title = {Epigenetics and the maintenance of developmental plasticity: extending the signalling theory framework.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {3}, pages = {1323-1338}, doi = {10.1111/brv.12396}, pmid = {29356358}, issn = {1469-185X}, abstract = {Developmental plasticity, a phenomenon of importance in both evolutionary biology and human studies of the developmental origins of health and disease (DOHaD), enables organisms to respond to their environment based on previous experience without changes to the underlying nucleotide sequence. Although such phenotypic responses should theoretically improve an organism's fitness and performance in its future environment, this is not always the case. Herein, we first discuss epigenetics as an adaptive mechanism of developmental plasticity and use signaling theory to provide an evolutionary context for DOHaD phenomena within a generation. Next, we utilize signalling theory to identify determinants of adaptive developmental plasticity, detect sources of random variability - also known as process errors that affect maintenance of an epigenetic signal (DNA methylation) over time, and discuss implications of these errors for an organism's health and fitness. Finally, we apply life-course epidemiology conceptual models to inform study design and analytical strategies that are capable of parsing out the potential effects of process errors in the relationships among an organism's early environment, DNA methylation, and phenotype in a future environment. Ultimately, we hope to foster cross-talk and interdisciplinary collaboration between evolutionary biology and DOHaD epidemiology, which have historically remained separate despite a shared interest in developmental plasticity.}, } @article {pmid29356321, year = {2018}, author = {Laubichler, MD and Prohaska, SJ and Stadler, PF}, title = {Toward a mechanistic explanation of phenotypic evolution: The need for a theory of theory integration.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {1}, pages = {5-14}, doi = {10.1002/jez.b.22785}, pmid = {29356321}, issn = {1552-5015}, mesh = {Animals ; *Biological Evolution ; Informatics ; Logic ; *Models, Biological ; }, abstract = {Reconciling different underlying ontologies and explanatory contexts has been one of the main challenges and impediments for theory integration in biology. Here, we analyze the challenge of developing an inclusive and integrative theory of phenotypic evolution as an example for the broader challenge of developing a theory of theory integration within the life sciences and suggest a number of necessary formal steps toward the resolution of often incompatible (hidden) assumptions. Theory integration in biology requires a better formal understanding of the structure of biological theories The strategy for integrating theories crucially depends on the relationships of the underlying ontologies.}, } @article {pmid29356270, year = {2018}, author = {Pančić, M and Kiørboe, T}, title = {Phytoplankton defence mechanisms: traits and trade-offs.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1269-1303}, doi = {10.1111/brv.12395}, pmid = {29356270}, issn = {1469-185X}, abstract = {In aquatic ecosystems, unicellular algae form the basis of the food webs. Theoretical and experimental studies have demonstrated that one of the mechanisms that maintain high diversity of phytoplankton is through predation and the consequent evolution of defence mechanisms. Proposed defence mechanisms in phytoplankton are diverse and include physiological (e.g. toxicity, bioluminescence), morphological (e.g. silica shell, colony formation), and behavioural (e.g. escape response) traits. However, the function of many of the proposed defence mechanisms remains elusive, and the costs and benefits (trade-offs) are often unquantified or undocumented. Here, we provide an overview of suggested phytoplankton defensive traits and review their experimental support. Wherever possible we quantify the trade-offs from experimental evidence and theoretical considerations. In many instances, experimental evidence suggests that defences are costless. However, we argue that (i) some costs materialize only under natural conditions, for example, sinking losses, or dependency on the availability of specific nutrients, and (ii) other costs become evident only under resource-deficient conditions where a rivalry for limiting resources between growth and defence occurs. Based on these findings, we suggest two strategies for quantifying the costs of defence mechanisms in phytoplankton: (i) for the evaluation of defence costs that are realized under natural conditions, a mechanistic understanding of the hypothesized component processes is required; and (ii) the magnitude of the costs (i.e. growth reduction) must be assessed under conditions of resource limitation.}, } @article {pmid29355854, year = {2018}, author = {Wagstaff, J and Löwe, J}, title = {Prokaryotic cytoskeletons: protein filaments organizing small cells.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {4}, pages = {187-201}, pmid = {29355854}, issn = {1740-1534}, support = {MC_U105184326//Medical Research Council/United Kingdom ; }, abstract = {Most, if not all, bacterial and archaeal cells contain at least one protein filament system. Although these filament systems in some cases form structures that are very similar to eukaryotic cytoskeletons, the term 'prokaryotic cytoskeletons' is used to refer to many different kinds of protein filaments. Cytoskeletons achieve their functions through polymerization of protein monomers and the resulting ability to access length scales larger than the size of the monomer. Prokaryotic cytoskeletons are involved in many fundamental aspects of prokaryotic cell biology and have important roles in cell shape determination, cell division and nonchromosomal DNA segregation. Some of the filament-forming proteins have been classified into a small number of conserved protein families, for example, the almost ubiquitous tubulin and actin superfamilies. To understand what makes filaments special and how the cytoskeletons they form enable cells to perform essential functions, the structure and function of cytoskeletal molecules and their filaments have been investigated in diverse bacteria and archaea. In this Review, we bring these data together to highlight the diverse ways that linear protein polymers can be used to organize other molecules and structures in bacteria and archaea.}, } @article {pmid29355853, year = {2018}, author = {York, A}, title = {Microbiome: Gut microbiota sways response to cancer immunotherapy.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {121}, pmid = {29355853}, issn = {1740-1534}, } @article {pmid29355852, year = {2018}, author = {Haldar, K and Bhattacharjee, S and Safeukui, I}, title = {Drug resistance in Plasmodium.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {156-170}, pmid = {29355852}, issn = {1740-1534}, support = {R01 HL130330/HL/NHLBI NIH HHS/United States ; }, abstract = {A marked decrease in malaria-related deaths worldwide has been attributed to the administration of effective antimalarials against Plasmodium falciparum, in particular, artemisinin-based combination therapies (ACTs). Increasingly, ACTs are also used to treat Plasmodium vivax, the second major human malaria parasite. However, resistance to frontline artemisinins and partner drugs is now causing the failure of P. falciparum ACTs in southeast Asia. In this Review, we discuss our current knowledge of markers and mechanisms of resistance to artemisinins and ACTs. In particular, we describe the identification of mutations in the propeller domains of Kelch 13 as the primary marker for artemisinin resistance in P. falciparum and explore two major mechanisms of resistance that have been independently proposed: the activation of the unfolded protein response and proteostatic dysregulation of parasite phosphatidylinositol 3- kinase. We emphasize the continuing challenges and the imminent need to understand mechanisms of resistance to improve parasite detection strategies, develop new combinations to eliminate resistant parasites and prevent their global spread.}, } @article {pmid29355604, year = {2018}, author = {Durães-Carvalho, R and Salemi, M}, title = {In-depth phylodynamics, evolutionary analysis and in silico predictions of universal epitopes of Influenza A subtypes and Influenza B viruses.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {174-182}, doi = {10.1016/j.ympev.2018.01.008}, pmid = {29355604}, issn = {1095-9513}, mesh = {Amino Acid Sequence ; Bayes Theorem ; *Computer Simulation ; Epitopes/chemistry/*genetics ; *Evolution, Molecular ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Host-Parasite Interactions ; Humans ; Influenza A virus/*genetics ; Influenza B virus/*genetics ; Influenza, Human/virology ; Likelihood Functions ; Neuraminidase/chemistry ; Peptides/chemistry ; *Phylogeny ; Phylogeography ; }, abstract = {This study applied High-Performance Computing to explore the high-resolution phylodynamics and the evolutionary dynamics of Influenza viruses (IVs) A and B and their subtypes in-depth to identify peptide-based candidates for broad-spectrum vaccine targets. For this purpose, we collected all the available Hemagglutinin (HA) and Neuraminidase (NA) nucleotide and amino acid sequences (more than 100,000) of IVs isolated from all the reservoirs and intermediate hosts species, from all geographic ranges and from different isolation sources, covering a period of almost one century of sampling years. We highlight that despite the constant changes in Influenza evolutionary dynamics over time, which are responsible for the generation of novel strains, our study identified the presence of highly conserved peptides distributed in all the HA and NA found in H1-H18 and N1-N11 IAV subtypes and IBVs. Additionally, predictions through computational methods showed that these peptides could have a strong affinity to bind to HLA-A∗02:01/HLA-DRB1∗01:01 major histocompatibility complex (MHC) class I and II molecules, therefore acting as a double ligand. Moreover, epitope prediction in antigens from pathogens responsible for secondary bacterial infection was also studied. These findings show that the regions mapped here may potentially be explored as universal epitope-based candidates to develop therapies leading to a broader response against the infection induced by all circulating IAVs, IBVs and Influenza-associated bacterial infections.}, } @article {pmid29355523, year = {2018}, author = {Gou, Y and Vemaraju, S and Sweet, EM and Kwon, HJ and Riley, BB}, title = {sox2 and sox3 Play unique roles in development of hair cells and neurons in the zebrafish inner ear.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {73-83}, pmid = {29355523}, issn = {1095-564X}, support = {R01 DC003806/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Fibroblast Growth Factors/genetics/metabolism ; Gene Expression Regulation, Developmental/*physiology ; Hair Cells, Auditory, Inner/cytology/*metabolism ; Neurogenesis/*physiology ; PAX2 Transcription Factor/genetics/metabolism ; Receptors, Notch/genetics/metabolism ; SOX Transcription Factors/*biosynthesis/genetics ; Zebrafish/*embryology ; Zebrafish Proteins/*biosynthesis/genetics/metabolism ; }, abstract = {Formation of neural and sensory progenitors in the inner ear requires Sox2 in mammals, and in other species is thought to rely on both Sox2 and Sox3. How Sox2 and/or Sox3 promote different fates is poorly understood. Our mutant analysis in zebrafish showed that sox2 is uniquely required for sensory development while sox3 is uniquely required for neurogenesis. Moderate misexpression of sox2 during placodal stages led to development of otic vesicles with expanded sensory and reduced neurogenic domains. However, high-level misexpression of sox2 or sox3 expanded both sensory and neurogenic domains to fill the medial and lateral halves of the otic vesicle, respectively. Disruption of medial factor pax2a eliminated the ability of sox2/3 misexpression to expand sensory but not neurogenic domains. Additionally, mild misexpression of fgf8 during placodal development was sufficient to specifically expand the zone of prosensory competence. Later, cross-repression between atoh1a and neurog1 helps maintain the sensory-neural boundary, but unlike mouse this does not require Notch activity. Together, these data show that sox2 and sox3 exhibit intrinsic differences in promoting sensory vs. neural competence, but at high levels these factors can mimic each other to enhance both states. Regional cofactors like pax2a and fgf8 also modify sox2/3 functions.}, } @article {pmid29355522, year = {2018}, author = {Gou, Y and Guo, J and Maulding, K and Riley, BB}, title = {sox2 and sox3 cooperate to regulate otic/epibranchial placode induction in zebrafish.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {84-95}, pmid = {29355522}, issn = {1095-564X}, support = {R01 DC003806/DC/NIDCD NIH HHS/United States ; }, mesh = {Animals ; Ear, Inner/*embryology ; *Mutation ; Organogenesis/*physiology ; PAX8 Transcription Factor/genetics/metabolism ; SOX Transcription Factors/genetics/*metabolism ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Expression of sox3 is one of the earliest markers of Fgf-dependent otic/epibranchial placode induction. We report here that sox2 is also expressed in the early otic/epibranchial placode in zebrafish. To address functions of sox2 and sox3, we generated knockouts and heat shock-inducible transgenes. Mutant analysis, and low-level misexpression, showed that sox2 and sox3 act redundantly to establish a full complement of otic/epibranchial cells. Disruption of pax8, another early regulator, caused similar placodal deficiencies to sox3 mutants or pax8-sox3 double mutants, suggesting that sox3 and pax8 operate in the same pathway. High-level misexpression of sox2 or sox3 during early stages cell-autonomously blocked placode induction, whereas misexpression several hours later could not reverse placodal differentiation. In an assay for ectopic placode-induction, we previously showed that misexpression of fgf8 induces a high level of ectopic sox3, but not pax8. Partial knockdown of sox3 significantly enhanced ectopic induction of pax8, whereas full knockdown of sox3 inhibited this process. Together these findings show that sox2 and sox3 are together required for proper otic induction, but the level of expression must be tightly regulated to avoid suppression of differentiation and maintenance of pluripotency.}, } @article {pmid29355521, year = {2018}, author = {Lacal Romero, J and Shen, Z and Baumgardner, K and Wei, J and Briggs, SP and Firtel, RA}, title = {The Dictyostelium GSK3 kinase GlkA coordinates signal relay and chemotaxis in response to growth conditions.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {56-72}, doi = {10.1016/j.ydbio.2018.01.007}, pmid = {29355521}, issn = {1095-564X}, support = {R01 GM033080/GM/NIGMS NIH HHS/United States ; R01 GM084227/GM/NIGMS NIH HHS/United States ; }, mesh = {Chemotaxis/*physiology ; Dictyostelium/*enzymology/genetics ; Gene Expression Regulation, Enzymologic/*physiology ; Glycogen Synthase Kinase 3/*biosynthesis/genetics ; Protozoan Proteins/*biosynthesis/genetics ; Signal Transduction/*physiology ; }, abstract = {GSK3 plays a central role in orchestrating key biological signaling pathways, including cell migration. Here, we identify GlkA as a GSK3 family kinase with functions that overlap with and are distinct from those of GskA. We show that GlkA, as previously shown for GskA, regulates the cell's cytoskeleton through MyoII assembly and control of Ras and Rap1 function, leading to aberrant cell migration. However, there are both qualitative and quantitative differences in the regulation of Ras and Rap1 and their downstream effectors, including PKB, PKBR1, and PI3K, with glkA- cells exhibiting a more severe chemotaxis phenotype than gskA- cells. Unexpectedly, the severe glkA- phenotypes, but not those of gskA-, are only exhibited when cells are grown attached to a substratum but not in suspension, suggesting that GlkA functions as a key kinase of cell attachment signaling. Using proteomic iTRAQ analysis we show that there are quantitative differences in the pattern of protein expression depending on the growth conditions in wild-type cells. We find that GlkA expression affects the cell's proteome during vegetative growth and development, with many of these changes depending on whether the cells are grown attached to a substratum or in suspension. These changes include key cytoskeletal and signaling proteins known to be essential for proper chemotaxis and signal relay during the aggregation stage of Dictyostelium development.}, } @article {pmid29353875, year = {2018}, author = {Payne, K and Gavan, SP and Wright, SJ and Thompson, AJ}, title = {Cost-effectiveness analyses of genetic and genomic diagnostic tests.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {235-246}, pmid = {29353875}, issn = {1471-0064}, support = {MR/N00583X/1//Medical Research Council/United Kingdom ; }, abstract = {Developments in next-generation sequencing technologies have driven the clinical application of diagnostic tests that interrogate the whole genome, which offer the chance to diagnose rare inherited diseases or inform the targeting of therapies. New genomic diagnostic tests compete with traditional approaches to diagnosis, including the genetic testing of single genes and other clinical strategies, for finite health-care budgets. In this context, decision analytic model-based cost-effectiveness analysis is a useful method to help evaluate the costs versus consequences of introducing new health-care interventions. This Perspective presents key methodological, technical, practical and organizational challenges that must be considered by decision-makers responsible for the allocation of health-care resources to obtain robust and timely information about the relative cost-effectiveness of the increasing numbers of emerging genomic tests.}, } @article {pmid29353874, year = {2018}, author = {Cloney, R}, title = {Technique: SNP-CLINGing onto your post in the genome.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {126-127}, pmid = {29353874}, issn = {1471-0064}, } @article {pmid29353873, year = {2018}, author = {Burgess, DJ}, title = {Functional genomics: A drop in an ocean of gene variants.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {126-127}, pmid = {29353873}, issn = {1471-0064}, } @article {pmid29353493, year = {2018}, author = {Winking, J}, title = {Exploring the Great Schism in the Social Sciences: Confirmation Bias and the Interpretation of Results Relating to Biological Influences on Human Behavior and Psychology.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704917752691}, doi = {10.1177/1474704917752691}, pmid = {29353493}, issn = {1474-7049}, mesh = {Bias ; Humans ; *Psychology ; *Social Sciences ; }, abstract = {The nature-nurture debate is one that biologists often dismiss as a false dichotomy, as all phenotypic traits are the results of complex processes of gene and environment interactions. However, such dismissiveness belies the ongoing debate that is unmistakable throughout the biological and social sciences concerning the role of biological influences in the development of psychological and behavioral traits in humans. Many have proposed that this debate is due to ideologically driven biases in the interpretation of results. Those favoring biological approaches have been accused of a greater willingness to accept biological explanations so as to rationalize or justify the status quo of inequality. Those rejecting biological approaches have been accused of an unwillingness to accept biological explanations so as to attribute inequalities solely to social and institutional factors, ultimately allowing for the possibility of social equality. While it is important to continue to investigate this topic through further research and debate, another approach is to examine the degree to which the allegations of bias are indeed valid. To accomplish this, a convenience sample of individuals with relevant postgraduate degrees was recruited from Mechanical Turk and social media. Participants were asked to rate the inferential power of different research designs and of mock results that varied in the degree to which they supported different ideologies. Results were suggestive that researchers harbor sincere differences of opinion concerning the inferential value of relevant research. There was no suggestion that ideological confirmation biases drive these differences. However, challenges associated with recruiting a large enough sample of experts as well as identifying believable mock scenarios limit the study's inferential scope.}, } @article {pmid29353439, year = {2018}, author = {Namai, S and Sugimoto, A}, title = {Transgenesis by microparticle bombardment for live imaging of fluorescent proteins in Pristionchus pacificus germline and early embryos.}, journal = {Development genes and evolution}, volume = {228}, number = {1}, pages = {75-82}, pmid = {29353439}, issn = {1432-041X}, support = {JP15K14503//Ministry of Education, Culture, Sports, Science and Technology/International ; JP15H04369//Ministry of Education, Culture, Sports, Science and Technology/International ; JP16932051//Japan Society for the Promotion of Science/International ; }, mesh = {3' Untranslated Regions ; Animals ; Chromadorea/embryology/*genetics ; *Gene Transfer Techniques ; Green Fluorescent Proteins/chemistry ; Hygromycin B/chemistry ; }, abstract = {Pristionchus pacificus is a free-living nematode used as a model organism for evolutionary developmental and ecological biology. Although a transgenic technique to form complex arrays by microinjection has been established in P. pacificus, transgene expression from the array in the germline and early embryos tends to be silenced. Here, we established a method to integrate transgenes into the genome of P. pacificus using microparticle bombardment with hygromycin B selection. Additionally, we isolated a mutant exhibiting significantly lower autofluorescence in the germline and early embryos, facilitating visualization of transgene-derived fluorescent proteins for live imaging. Transgenic lines constructed using these tools successfully expressed GFP-tagged proteins in the germline and early embryos and enabled live imaging of chromosomes, microtubules, and centrosomes.}, } @article {pmid29353421, year = {2018}, author = {Su, T and Liu, R and Long, Y and Quan, S and Lai, S and Wang, L and Si, J and Chen, S}, title = {1-Day or 5-Day Fecal Samples, Which One is More Beneficial to be Used for DNA-Based Gut Microbiota Study.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {288-295}, pmid = {29353421}, issn = {1432-0991}, support = {81472214//National Natural Science Foundation of China/ ; 2013TD13//Zhejiang province key science and technology innovation team/ ; }, mesh = {Adult ; Bacteria/classification/genetics/*isolation & purification ; Biodiversity ; DNA, Bacterial/*genetics ; Feces/*microbiology ; Female ; *Gastrointestinal Microbiome ; Humans ; Male ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Time Factors ; }, abstract = {Fecal sample collection is an important influential factor for DNA-based gut microbiota study. It is controversial whether the microbiome detected in fecal sample collected at one random day could fully represent the gut microbial community. The aim of the study is to figure out whether the use of fecal sample mixture collected at consecutive 5 days could more accurately represent gut microbial community. 1- and 5-day fecal samples were collected from 8 healthy adults and analyzed by 16S rRNA sequence. Our results indicated that both 1-day fecal samples and 5-day samples exhibited relatively high repeatability. The relative abundance of majority of bacterial taxa did not changed between 1-day fecal samples and 5-day fecal samples. However, the alpha diversity of 5-day fecal samples was higher than that of 1-day fecal samples. When the aims of studies are to analyze the relative abundance of specific OTUs among subjects, fecal samples collected at one day could be used. When microbial diversity is one of essential factors to be analyzed, the use of 5-day fecal samples may be more recommended.}, } @article {pmid29353420, year = {2018}, author = {Jałowiecki, Ł and Żur, J and Chojniak, J and Ejhed, H and Płaza, G}, title = {Properties of Antibiotic-Resistant Bacteria Isolated from Onsite Wastewater Treatment Plant in Relation to Biofilm Formation.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {639-649}, pmid = {29353420}, issn = {1432-0991}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/classification/*drug effects/*isolation & purification ; Bacterial Physiological Phenomena ; *Biofilms ; Waste Water/*microbiology ; Water Purification/*instrumentation ; }, abstract = {The aim of the present study was to determine some properties of antibiotic-resistant bacterial strains isolated from onsite wastewater technology in relation to biofilm formation, e.g., autoaggregation and motility. Additionally, biosurfactant production by the isolates was also evaluated. The ability of selected strains to develop a biofilm was assessed by using the crystal violet method, which allows to indirectly quantify the attached bacterial biomass (live, dead cells, and polysaccharides as well). Obtained results showed that 19 of the analyzed strains were able to produce biofilm after 72 h of incubation. The low values of surface tension in the range between 28 and 36 mN/m were observed in the bacteria, which are not able to produce biofilm or be classified as weak biofilm producers. Among biofilm-forming strains the highest autoaggregation index was observed for Mycobacterium brumae and Bacillus alcalophilus. Noteworthy, that some strains capable of biofilm formation showed no aggregation abilities or were characterized by low autoaggregative properties. The results of visual autoaggregation assay showed no visible flocs after given time of incubation. The results from motility test demonstrated that most of the analyzed strains were motile. Noteworthy, that up to now literature data about physiology, biofilm formation, and autoaggregative capabilities of bacteria isolated from onsite wastewater technology are very limited and this paper gives the information on the antibiotic-resistant bacteria with ability to form biofilm. Thus, the present study points to develop novel bioinocula in antibiotic degradation and to reach novel biofilm-dispersing agents produced by various bacteria that can be used as disinfectants or surface-coating agents to prevent microbial surface colonization and biofilm development.}, } @article {pmid29352963, year = {2018}, author = {Acuna, A and Drakopoulos, MA and Leng, Y and Goergen, CJ and Calve, S}, title = {Three-dimensional visualization of extracellular matrix networks during murine development.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {122-129}, pmid = {29352963}, issn = {1095-564X}, support = {DP2 AT009833/AT/NCCIH NIH HHS/United States ; R01 AR071359/AR/NIAMS NIH HHS/United States ; R03 AR065201/AR/NIAMS NIH HHS/United States ; R21 AR069248/AR/NIAMS NIH HHS/United States ; }, mesh = {Acrylic Resins ; Animals ; Detergents/pharmacology ; *Embryonic Development ; Epidermis/ultrastructure ; Extracellular Matrix/*ultrastructure ; Extracellular Matrix Proteins/drug effects/ultrastructure ; Fluorescent Dyes ; Forelimb/embryology/ultrastructure ; Formaldehyde ; Hydrogels ; Mice ; Mice, Inbred C57BL ; Microscopy, Confocal/*methods ; Morphogenesis ; Polymers ; Proteoglycans/analysis ; Sodium Dodecyl Sulfate/pharmacology ; Specimen Handling ; Staining and Labeling/methods ; Tendons/embryology/ultrastructure ; Tissue Embedding/*methods ; Tissue Fixation ; }, abstract = {The extracellular matrix (ECM) plays a crucial role in embryogenesis, serving both as a substrate to which cells attach and as an active regulator of cell behavior. However, little is known about the spatiotemporal expression patterns and 3D structure of ECM proteins during embryonic development. The lack of suitable methods to visualize the embryonic ECM is largely responsible for this gap, posing a major technical challenge for biologists and tissue engineers. Here, we describe a method of viewing the 3D organization of the ECM using a polyacrylamide-based hydrogel to provide a 3D framework within developing murine embryos. After removal of soluble proteins using sodium dodecyl sulfate, confocal microscopy was used to visualize the 3D distribution of independent ECM networks in multiple developing tissues, including the forelimb, eye, and spinal cord. Comparative analysis of E12.5 and E14.5 autopods revealed proteoglycan-rich fibrils maintain connections between the epidermis and the underlying tendon and cartilage, indicating a role for the ECM during musculoskeletal assembly and demonstrating that our method can be a powerful tool for defining the spatiotemporal distribution of the ECM during embryogenesis.}, } @article {pmid29352811, year = {2018}, author = {Misawa, K and Tarumoto, N and Tamura, S and Osa, M and Hamamoto, T and Yuki, A and Kouzaki, Y and Imai, K and Ronald, RL and Yamaguchi, T and Murakami, T and Maesaki, S and Suzuki, Y and Kawana, A and Maeda, T}, title = {Single nucleotide polymorphisms in genes encoding penicillin-binding proteins in β-lactamase-negative ampicillin-resistant Haemophilus influenzae in Japan.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {53}, pmid = {29352811}, issn = {1756-0500}, mesh = {Ampicillin/*pharmacology ; Ampicillin Resistance/genetics ; Anti-Bacterial Agents/pharmacology ; Bacterial Proteins/*genetics ; Genotype ; Haemophilus Infections/microbiology ; Haemophilus influenzae/drug effects/*genetics/metabolism ; Humans ; Microbial Sensitivity Tests ; Penicillin-Binding Proteins/*genetics ; *Polymorphism, Single Nucleotide ; beta-Lactamases/metabolism ; }, abstract = {OBJECTIVE: β-Lactamase-negative ampicillin-resistant Haemophilus influenzae is a common opportunistic pathogen of hospital- and community-acquired infections, harboring multiple single nucleotide polymorphisms in the ftsI gene, which codes for penicillin-binding protein-3. The objectives of this study were to perform comprehensive genetic analyses of whole regions of the penicillin-binding proteins in H. influenzae and to identify additional single nucleotide polymorphisms related to antibiotic resistance, especially to ampicillin and other cephalosporins.

RESULTS: In this genome analysis of the ftsI gene in 27 strains of H. influenzae, 10 of 23 (43.5%) specimens of group III genotype β-lactamase-negative ampicillin-resistant H. influenzae were paradoxically classified as ampicillin-sensitive phenotypes. Unfortunately, we could not identify any novel mutations that were significantly associated with ampicillin minimum inhibitory concentrations in other regions of the penicillin-binding proteins, and we reconfirmed that susceptibility to β-lactam antibiotics was mainly defined by previously reported SNPs in the ftsI gene. We should also consider detailed changes in expression that lead to antibiotic resistance in the future because the acquisition of resistance to antimicrobials can be predicted by the expression levels of a small number of genes.}, } @article {pmid29352810, year = {2018}, author = {Yu, JQ and Wang, JH and Sun, CH and Zhang, QY and Hu, DG and Hao, YJ}, title = {Ectopic expression of the apple nucleus-encoded thylakoid protein MdY3IP1 triggers early-flowering and enhanced salt-tolerance in Arabidopsis thaliana.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {18}, pmid = {29352810}, issn = {1471-2229}, support = {31601728//National Natural Science Foundation of China/International ; 31325024 and 31430074//National Natural Science Foundation of China/International ; ZR2016CQ13 and SDAIT-06-03//Natural Science Foundation of Shandong Province/International ; 564024//Young Scientists Funds of Shandong Agricultural University/International ; 24024//Youth Science and Technology Innovation Fund of Shandong Agricultural University/International ; IRT15R42//Changjiang Scholar Program of Chinese Ministry of Education/International ; }, mesh = {Arabidopsis/*genetics/metabolism ; *Ectopic Gene Expression ; Flowers/genetics/growth & development/*physiology ; Malus/*genetics ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified/genetics/metabolism ; Salt Tolerance/*genetics ; Thylakoids/metabolism ; }, abstract = {BACKGROUND: The roles in photosystem I (PSI) assembly of the nucleus-encoded thylakoid protein Y3IP1 who interacts with the plastid-encoded Ycf3 protein that has been well-characterized in plants. However, its function and potential mechanisms in other aspects remain poorly understood.

RESULTS: We identified the apple MdY3IP1 gene, which encodes a protein highly homologous to the Arabidopsis Y3IP1 (AtY3IP1). Ectopic expression of MdY3IP1 triggered early-flowering and enhanced salt tolerance in Arabidopsis plants. MdY3IP1 controlled floral transition by accelerating sugar metabolism process in plant cells, thereby influencing the expression of flowering-associated genes. The increase in salt stress tolerance in MdY3IP1-expressing plants correlated with reduced reactive oxygen species (ROS) accumulation, and an increase in lateral root development by regulating both auxin biosynthesis and transport, as followed by enhancement of salt tolerance in Arabidopsis. Overall, these findings provide new evidences for additional functions of Y3IP1-like proteins and their underlying mechanisms of which Y3IP1 confers early-flowering and salt tolerance phenotypes in plants.

CONCLUSIONS: These observations suggest that plant growth and stress resistance can be affected by the regulation of the MdY3IP1 gene. Further molecular and genetic approaches will accelerate our knowledge of MdY3IP1 functions in PSI complex formation and plants stress resistance, and inform strategies for creating transgenic crop varieties with early maturity and high-resistant to adverse environmental conditions.}, } @article {pmid29352613, year = {2018}, author = {Kapur, M and Ackerman, SL}, title = {mRNA Translation Gone Awry: Translation Fidelity and Neurological Disease.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {218-231}, pmid = {29352613}, issn = {0168-9525}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 NS094637/NS/NINDS NIH HHS/United States ; R21 NS096600/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; Models, Genetic ; *Mutation ; Nervous System Diseases/*genetics ; Protein Biosynthesis/*genetics ; RNA, Messenger/*genetics ; Saccharomyces cerevisiae/genetics ; Transfer RNA Aminoacylation/genetics ; }, abstract = {Errors during mRNA translation can lead to a reduction in the levels of functional proteins and an increase in deleterious molecules. Advances in next-generation sequencing have led to the discovery of rare genetic disorders, many caused by mutations in genes encoding the mRNA translation machinery, as well as to a better understanding of translational dynamics through ribosome profiling. We discuss here multiple neurological disorders that are linked to errors in tRNA aminoacylation and ribosome decoding. We draw on studies from genetic models, including yeast and mice, to enhance our understanding of the translational defects observed in these diseases. Finally, we emphasize the importance of tRNA, their associated enzymes, and the inextricable link between accuracy and efficiency in the maintenance of translational fidelity.}, } @article {pmid29352037, year = {2018}, author = {Frith, U}, title = {Preface.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, doi = {10.1098/rstb.2017.0361}, pmid = {29352037}, issn = {1471-2970}, mesh = {Animals ; Humans ; Mental Disorders/*therapy ; *Mental Health ; Mice/*psychology ; *Translational Medical Research ; }, } @article {pmid29352036, year = {2018}, author = {Visser, RM and Lau-Zhu, A and Henson, RN and Holmes, EA}, title = {Multiple memory systems, multiple time points: how science can inform treatment to control the expression of unwanted emotional memories.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352036}, issn = {1471-2970}, support = {MC_U105579226//Medical Research Council/United Kingdom ; MC_UP_0901/1//Medical Research Council/United Kingdom ; SUAI/010/ RG91365//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Anxiety Disorders/*therapy ; *Emotions ; Humans ; *Memory ; }, abstract = {Memories that have strong emotions associated with them are particularly resilient to forgetting. This is not necessarily problematic, however some aspects of memory can be. In particular, the involuntary expression of those memories, e.g. intrusive memories after trauma, are core to certain psychological disorders. Since the beginning of this century, research using animal models shows that it is possible to change the underlying memory, for example by interfering with its consolidation or reconsolidation. While the idea of targeting maladaptive memories is promising for the treatment of stress and anxiety disorders, a direct application of the procedures used in non-human animals to humans in clinical settings is not straightforward. In translational research, more attention needs to be paid to specifying what aspect of memory (i) can be modified and (ii) should be modified. This requires a clear conceptualization of what aspect of memory is being targeted, and how different memory expressions may map onto clinical symptoms. Furthermore, memory processes are dynamic, so procedural details concerning timing are crucial when implementing a treatment and when assessing its effectiveness. To target emotional memory in its full complexity, including its malleability, science cannot rely on a single method, species or paradigm. Rather, a constructive dialogue is needed between multiple levels of research, all the way 'from mice to mental health'.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352035, year = {2018}, author = {St Clair, D and Johnstone, M}, title = {Using mouse transgenic and human stem cell technologies to model genetic mutations associated with schizophrenia and autism.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352035}, issn = {1471-2970}, support = {100135//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Animals, Genetically Modified ; Autistic Disorder/*genetics ; *Disease Models, Animal ; Humans ; Induced Pluripotent Stem Cells/*physiology ; Mice ; *Mutation ; Schizophrenia/*genetics ; }, abstract = {Solid progress has occurred over the last decade in our understanding of the molecular genetic basis of neurodevelopmental disorders, and of schizophrenia and autism in particular. Although the genetic architecture of both disorders is far more complex than previously imagined, many key loci have at last been identified. This has allowed in vivo and in vitro technologies to be refined to model specific high-penetrant genetic loci involved in both disorders. Using the DISC1/NDE1 and CYFIP1/EIF4E loci as exemplars, we explore the opportunities and challenges of using animal models and human-induced pluripotent stem cell technologies to further understand/treat and potentially reverse the worst consequences of these debilitating disorders.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352034, year = {2018}, author = {Robinson, ESJ}, title = {Translational new approaches for investigating mood disorders in rodents and what they may reveal about the underlying neurobiology of major depressive disorder.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352034}, issn = {1471-2970}, support = {MR/L011212/1//Medical Research Council/United Kingdom ; 095029//Wellcome Trust/United Kingdom ; BB/N015762/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L009137/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Depressive Disorder, Major/physiopathology/psychology ; Disease Models, Animal ; Mice ; Mood Disorders/*physiopathology/*psychology ; Rats ; *Translational Medical Research ; }, abstract = {Mood disorders represent one of society's most costly and challenging health burdens. The drug treatments used today were initially discovered serendipitously in the 1950s. Animal models were then developed based on the ability of these drugs to alter specific behaviours. These models have played a major role in the development of the second generation of antidepressants. However, their use has been heavily criticized, particularly in relation to whether they recapitulate similar underlying biology to the psychiatric disorder they are proposed to represent. This article considers our work in the field of affective bias and the development of a translational research programme to try to develop and validate better animal models. We discuss whether the new data that have arisen from these studies support an alternative perspective on the underlying neurobiological processes that lead to major depressive disorder (MDD). Specifically, this article will consider whether a neuropsychological mechanism involving affective biases plays a causal role in the development of MDD and its associated emotional and behavioural symptoms. These animal studies also raise the possibility that neuropsychological mechanisms involving affective biases are a precursor to, rather than a consequence of, the neurotrophic changes linked to MDD.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352033, year = {2018}, author = {Shumake, J and Jones, C and Auchter, A and Monfils, MH}, title = {Data-driven criteria to assess fear remission and phenotypic variability of extinction in rats.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352033}, issn = {1471-2970}, mesh = {Animals ; *Biological Variation, Population ; *Conditioning (Psychology) ; *Extinction, Psychological ; Fear/*psychology ; Female ; Individuality ; Male ; Rats ; Rats, Long-Evans ; Rats, Sprague-Dawley ; }, abstract = {Fear conditioning is widely employed to examine the mechanisms that underlie dysregulations of the fear system. Various manipulations are often used following fear acquisition to attenuate fear memories. In rodent studies, freezing is often the main output measure to quantify 'fear'. Here, we developed data-driven criteria for defining a standard benchmark that indicates remission from conditioned fear and for identifying subgroups with differential treatment responses. These analyses will enable a better understanding of individual differences in treatment responding.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352032, year = {2018}, author = {Kindt, M}, title = {The surprising subtleties of changing fear memory: a challenge for translational science.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352032}, issn = {1471-2970}, mesh = {Animals ; *Fear ; Humans ; *Memory ; Memory Consolidation ; *Translational Medical Research ; }, abstract = {Current pharmacological and psychological treatments for disorders of emotional memory only dampen the affective response while leaving the original fear memory intact. Under adverse circumstances, these original memories regain prominence, causing relapses in many patients. The (re)discovery in neuroscience that after reactivation consolidated fear memories may return to a transient labile state, requiring a process of restabilization in order to persist, offers a window of opportunity for modifying fear memories with amnestic agents. This process, known as memory reconsolidation, opens avenues for developing a revolutionary treatment for emotional memory disorders. The reconsolidation intervention challenges the dominant pharmacological and psychological models of treatment: it is only effective when the amnestic drug is given in conjunction with memory reactivation during a specific time window, and a modification of cognitive processes is a boundary condition for changing fear. Notwithstanding the dramatic effects of targeting memory reconsolidation in the laboratory (i.e. proof of principle), the greatest hurdle to overcome is that the success of the manipulation depends on subtle differences in the reactivation procedure. These experimental parameters cannot be easily controlled in clinical practice. In harnessing the clinical potential of memory reconsolidation, a heuristic for bi-directionally translating behavioural neuroscience and clinical science is proposed.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352031, year = {2018}, author = {Canetta, S and Kellendonk, C}, title = {Can we use mice to study schizophrenia?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352031}, issn = {1471-2970}, support = {K01 MH107760/MH/NIMH NIH HHS/United States ; R01 MH093672/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; *Disease Models, Animal ; Humans ; *Mice ; Schizophrenia/*etiology/genetics/physiopathology ; }, abstract = {The validity of rodent models for the study of psychiatric disorders is controversial. Despite great efforts from academic institutions and pharmaceutical companies, as of today, no major therapeutic intervention has been developed for the treatment of psychiatric disorders based on mechanistic insights from rodent models. Here, we argue that despite these historical shortcomings, rodent studies are nevertheless instrumental for identifying neuronal circuit mechanisms underlying behaviours that are affected in psychiatric disorders. Focusing on schizophrenia, we will give four examples of rodent models that were generated based on genetic and environmental risk factors or pathophysiological evidence as entry points. We will then discuss how circuit analysis in these specific examples can be used for testing hypotheses about neuronal mechanisms underlying symptoms of schizophrenia, which will then guide the development of new therapies.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352030, year = {2018}, author = {Hyman, SE}, title = {The daunting polygenicity of mental illness: making a new map.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352030}, issn = {1471-2970}, mesh = {Genomics ; Humans ; Mental Disorders/*genetics ; Multifactorial Inheritance/*genetics ; *Phenotype ; }, abstract = {An epochal opportunity to elucidate the pathogenic mechanisms of psychiatric disorders has emerged from advances in genomic technology, new computational tools and the growth of international consortia committed to data sharing. The resulting large-scale, unbiased genetic studies have begun to yield new biological insights and with them the hope that a half century of stasis in psychiatric therapeutics will come to an end. Yet a sobering picture is coming into view; it reveals daunting genetic and phenotypic complexity portending enormous challenges for neurobiology. Successful exploitation of results from genetics will require eschewal of long-successful reductionist approaches to investigation of gene function, a commitment to supplanting much research now conducted in model organisms with human biology, and development of new experimental systems and computational models to analyse polygenic causal influences. In short, psychiatric neuroscience must develop a new scientific map to guide investigation through a polygenic terra incognitaThis article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352029, year = {2018}, author = {Walsh, AEL and Browning, M and Drevets, WC and Furey, M and Harmer, CJ}, title = {Dissociable temporal effects of bupropion on behavioural measures of emotional and reward processing in depression.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352029}, issn = {1471-2970}, mesh = {Adult ; Antidepressive Agents, Second-Generation/administration & dosage/*pharmacology ; Bupropion/administration & dosage/*pharmacology ; Depression/*drug therapy ; Emotions/*drug effects ; Female ; Humans ; Male ; *Reward ; Time Factors ; Young Adult ; }, abstract = {Antidepressants remediate negative biases in emotional processing early in treatment, prior to mood improvement. However, the effects on reward processing potentially relevant to the treatment of anhedonia are less clear. Here we investigate the early and sustained effects of the dopamine and noradrenaline reuptake inhibitor bupropion on behavioural measures of emotional and reward processing in currently depressed individuals. Forty-six currently depressed patients and 42 healthy controls participated in a repeated measures study, during which open-label bupropion was administered to only the patient group over a six week period without a placebo group. All participants completed the Emotional Test Battery and a probabilistic instrumental learning task at week 0, week 2 and week 6. Currently depressed patients displayed negative biases in emotional processing and blunted response bias for high-probability wins compared to the healthy controls at baseline. Bupropion was found to reduce the negative biases in emotional processing early in treatment, including a significant decrease in the percentage misclassification of other face emotions as sad and the number of negative self-referent words falsely recalled between baseline and week 2. Conversely, bupropion was found to initially further reduce the response bias for high-probability wins between baseline and week 2. This effect reversed with six weeks' bupropion treatment and reward processing was normalized compared to the healthy controls. Early in treatment, bupropion acts to reduce negative biases in emotional processing but exacerbates impaired reward processing. The beneficial actions of bupropion on reward processing then occur later in treatment. Such dissociation in the temporal effects of bupropion on emotional and reward processing has implications for the treatment of the different symptom domains of negative affect and anhedonia in depression.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352028, year = {2018}, author = {Albo, Z and Gräff, J}, title = {The mysteries of remote memory.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352028}, issn = {1471-2970}, support = {678832//European Research Council/International ; }, mesh = {Animals ; Cell Nucleus/*physiology ; Memory, Long-Term/*physiology ; Mice ; Synapses/*physiology ; }, abstract = {Long-lasting memories form the basis of our identity as individuals and lie central in shaping future behaviours that guide survival. Surprisingly, however, our current knowledge of how such memories are stored in the brain and retrieved, as well as the dynamics of the circuits involved, remains scarce despite seminal technical and experimental breakthroughs in recent years. Traditionally, it has been proposed that, over time, information initially learnt in the hippocampus is stored in distributed cortical networks. This process-the standard theory of memory consolidation-would stabilize the newly encoded information into a lasting memory, become independent of the hippocampus, and remain essentially unmodifiable throughout the lifetime of the individual. In recent years, several pieces of evidence have started to challenge this view and indicate that long-lasting memories might already ab ovo be encoded, and subsequently stored in distributed cortical networks, akin to the multiple trace theory of memory consolidation. In this review, we summarize these recent findings and attempt to identify the biologically plausible mechanisms based on which a contextual memory becomes remote by integrating different levels of analysis: from neural circuits to cell ensembles across synaptic remodelling and epigenetic modifications. From these studies, remote memory formation and maintenance appear to occur through a multi-trace, dynamic and integrative cellular process ranging from the synapse to the nucleus, and represent an exciting field of research primed to change quickly as new experimental evidence emerges.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352027, year = {2018}, author = {Huang, AS and Mitchell, JA and Haber, SN and Alia-Klein, N and Goldstein, RZ}, title = {The thalamus in drug addiction: from rodents to humans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352027}, issn = {1471-2970}, support = {R01 DA041528/DA/NIDA NIH HHS/United States ; R21 DA040046/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Drug-Seeking Behavior/*physiology ; Humans ; Rodentia/*physiology ; Substance-Related Disorders/diagnostic imaging/*physiopathology ; Thalamus/diagnostic imaging/*physiopathology ; }, abstract = {Impairments in response inhibition and salience attribution (iRISA) have been proposed to underlie the clinical symptoms of drug addiction as mediated by cortico-striatal-thalamo-cortical networks. The bulk of evidence supporting the iRISA model comes from neuroimaging research that has focused on cortical and striatal influences with less emphasis on the role of the thalamus. Here, we highlight the importance of the thalamus in drug addiction, focusing on animal literature findings on thalamic nuclei in the context of drug-seeking, structural and functional changes of the thalamus as measured by imaging studies in human drug addiction, particularly during drug cue and non-drug reward processing, and response inhibition tasks. Findings from the animal literature suggest that the paraventricular nucleus of the thalamus, the lateral habenula and the mediodorsal nucleus may be involved in the reinstatement, extinction and expression of drug-seeking behaviours. In support of the iRISA model, the human addiction imaging literature demonstrates enhanced thalamus activation when reacting to drug cues and reduced thalamus activation during response inhibition. This pattern of response was further associated with the severity of, and relapse in, drug addiction. Future animal studies could widen their field of focus by investigating the specific role(s) of different thalamic nuclei in different phases of the addiction cycle. Similarly, future human imaging studies should aim to specifically delineate the structure and function of different thalamic nuclei, for example, through the application of advanced imaging protocols at higher magnetic fields (7 Tesla).This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352026, year = {2018}, author = {Everitt, BJ and Giuliano, C and Belin, D}, title = {Addictive behaviour in experimental animals: prospects for translation.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352026}, issn = {1471-2970}, support = {RG82507//Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Behavior, Addictive ; Cocaine ; *Conditioning, Operant ; *Cues ; Disease Models, Animal ; Humans ; Memory ; Mice/*psychology ; Pharmaceutical Preparations ; Primates/*psychology ; Rats/*psychology ; Reinforcement (Psychology) ; Reward ; *Translational Medical Research ; }, abstract = {Since the introduction of intravenous drug self-administration methodology over 50 years ago, experimental investigation of addictive behaviour has delivered an enormous body of data on the neural, psychological and molecular mechanisms of drug reward and reinforcement and the neuroadaptations to chronic use. Whether or not these behavioural and molecular studies are viewed as modelling the underpinnings of addiction in humans, the discussion presented here highlights two areas-the impact of drug-associated conditioned stimuli-or drug cues-on drug seeking and relapse, and compulsive cocaine seeking. The degree to which these findings translate to the clinical state of addiction is considered in terms of the underlying neural circuitry and also the ways in which this understanding has helped develop new treatments for addiction. The psychological and neural mechanisms underlying drug memory reconsolidation and extinction established in animal experiments show particular promise in delivering new treatments for relapse prevention to the clinic.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352025, year = {2018}, author = {Craske, MG and Hermans, D and Vervliet, B}, title = {State-of-the-art and future directions for extinction as a translational model for fear and anxiety.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352025}, issn = {1471-2970}, mesh = {Animals ; Anxiety Disorders/*therapy ; *Conditioning, Classical ; *Extinction, Psychological ; Fear/*physiology/*psychology ; Humans ; Mice ; Translational Medical Research ; }, abstract = {Through advances in both basic and clinical scientific research, Pavlovian fear conditioning and extinction have become an exemplary translational model for understanding and treating anxiety disorders. Discoveries in associative and neurobiological mechanisms underlying extinction have informed techniques for optimizing exposure therapy that enhance the formation of inhibitory associations and their consolidation and retrieval over time and context. Strategies that enhance formation include maximizing prediction-error correction by violating expectancies, deepened extinction, occasional reinforced extinction, attentional control and removal of safety signals/behaviours. Strategies that enhance consolidation include pharmacological agonists of NMDA (i.e. d-cycloserine) and mental rehearsal. Strategies that enhance retrieval include multiple contexts, retrieval cues, and pharmacological blockade of contextual encoding. Stimulus variability and positive affect are posited to influence the formation and the retrieval of inhibitory associations. Inhibitory regulation through affect labelling is considered a complement to extinction. The translational value of extinction will be increased by more investigation of elements central to extinction itself, such as extinction generalization, and interactions with other learning processes, such as instrumental avoidance reward learning, and with other clinically relevant cognitive-emotional processes, such as self-efficacy, threat appraisal and emotion regulation, will add translational value. Moreover, framing fear extinction and related processes within a developmental context will increase their clinical relevance.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352024, year = {2018}, author = {Moore, CF and Panciera, JI and Sabino, V and Cottone, P}, title = {Neuropharmacology of compulsive eating.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352024}, issn = {1471-2970}, support = {F31 DA044664/DA/NIDA NIH HHS/United States ; }, mesh = {Food Addiction/etiology/*physiopathology ; Humans ; Neuropharmacology ; }, abstract = {Compulsive eating behaviour is a transdiagnostic construct observed in certain forms of obesity and eating disorders, as well as in the proposed construct of 'food addiction'. Compulsive eating can be conceptualized as comprising three elements: (i) habitual overeating, (ii) overeating to relieve a negative emotional state, and (iii) overeating despite adverse consequences. Neurobiological processes that include maladaptive habit formation, the emergence of a negative affect, and dysfunctions in inhibitory control are thought to drive the development and persistence of compulsive eating behaviour. These complex psychobehavioural processes are under the control of various neuropharmacological systems. Here, we describe the current evidence implicating these systems in compulsive eating behaviour, and contextualize them within the three elements. A better understanding of the neuropharmacological substrates of compulsive eating behaviour has the potential to significantly advance the pharmacotherapy for feeding-related pathologies.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352023, year = {2018}, author = {Wood, J and LaPalombara, Z and Ahmari, SE}, title = {Monoamine abnormalities in the SAPAP3 knockout model of obsessive-compulsive disorder-related behaviour.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352023}, issn = {1471-2970}, support = {R01 MH104255/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Biogenic Monoamines/*metabolism ; Chromatography, High Pressure Liquid ; Disease Models, Animal ; Female ; Humans ; Male ; Mice ; Mice, Knockout ; Obsessive-Compulsive Disorder/metabolism/*physiopathology ; Prefrontal Cortex/metabolism ; Serotonin/*metabolism ; Ventral Striatum/metabolism ; }, abstract = {Obsessive-compulsive disorder (OCD) is a leading cause of illness-related disability, but the neural mechanisms underlying OCD symptoms are unclear. One potential mechanism of OCD pathology is monoamine dysregulation. Because of the difficulty of studying monoamine signalling in patients, animal models offer a viable alternative to understanding this aspect of OCD pathophysiology. We used HPLC to characterize post-mortem monoamine levels in lateral orbitofrontal cortex (OFC), medial OFC, medial prefrontal cortex and dorsal and ventral striatum of SAPAP-3 knockout (KO) mice, a well-validated model of compulsive-like behaviours in OCD. As predicted from previous studies, excessive grooming was significantly increased in SAPAP-3 KO mice. Overall levels of the serotonin metabolite 5-hydroxyindoleacetic acid (HIAA) and the ratio of 5HIAA/serotonin (serotonin turnover) were increased in all cortical and striatal regions examined. In addition, dihydroxyphenylacetic acid/dopamine ratio was increased in lateral OFC, and HVA/dopamine ratio was increased in lateral and medial OFC. No baseline differences in serotonin or dopamine tissue content were observed. These data provide evidence of monoaminergic dysregulation in a translational model of OCD symptoms and are consistent with aberrant cortical and striatal serotonin and dopamine release/metabolism in SAPAP-3 KO mice. These results are guiding ongoing experiments using circuit and cell-type specific manipulations of dopamine and serotonin to determine the contributions of these monoaminergic systems to compulsive behaviours, and serve here as a touchstone for an expanded discussion of these techniques for precise circuit dissection.This article is part of the discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29352022, year = {2018}, author = {Milton, AL and Holmes, EA}, title = {Of mice and mental health: facilitating dialogue and seeing further.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1742}, pages = {}, pmid = {29352022}, issn = {1471-2970}, support = {MR/N02530X/1//Medical Research Council/United Kingdom ; 200710/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Mental Disorders/*therapy ; *Mental Health ; Mice/*psychology ; *Translational Medical Research ; }, abstract = {The science of mental life is critical for understanding both how we function, and impairments in our functioning. However, understanding the causal mechanisms underlying mental health disorders and developing new treatments are challenges too great to be solved by any individual approach. There is a growing awareness that translational research-from laboratory to patient and back again to animal models-will be critical for the improved understanding and treatment of mental health disorders. The motivation and intention to pursue translational approaches is therefore strong in mental health research, but critically, opportunities for interaction between basic scientists and clinicians are relatively limited, and vary depending on the institution in which researchers are working. This has promoted the development of a 'culture gap' between basic and clinical scientists that limits interaction and sharing of knowledge. Here, we provide 14 examples of contemporary translational research and call for an increased collaborative approach to mental health research that spans clinical diagnoses, levels of analysis and bridges between basic to clinical mental health sciences, including, but not limited to, psychology and neuroscience. What is needed is an inclusive and integrated approach, bringing together scientists working at all levels of enquiry with clinicians providing insights on what works (and what does not). To stimulate the much-needed innovation in therapeutic techniques, an analysis of component parts is critical. Our approach suggests simplifying complex behaviours into distinct psychological components. Asking collaboratively driven scientific questions about dysfunction will also benefit our fundamental understanding of mental life.This article is part of a discussion meeting issue 'Of mice and mental health: facilitating dialogue between basic and clinical neuroscientists'.}, } @article {pmid29351994, year = {2018}, author = {Righini, M and Lee, A and Cañari-Chumpitaz, C and Lionberger, T and Gabizon, R and Coello, Y and Tinoco, I and Bustamante, C}, title = {Full molecular trajectories of RNA polymerase at single base-pair resolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1286-1291}, pmid = {29351994}, issn = {1091-6490}, support = {R01 GM032543/GM/NIGMS NIH HHS/United States ; R01 GM071552/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {*Algorithms ; Base Pairing ; DNA-Directed RNA Polymerases/*chemistry/genetics ; Diphosphates/chemistry ; Escherichia coli Proteins/chemistry/genetics ; Markov Chains ; *Optical Tweezers ; }, abstract = {In recent years, highly stable optical tweezers systems have enabled the characterization of the dynamics of molecular motors at very high resolution. However, the motion of many motors with angstrom-scale dynamics cannot be consistently resolved due to poor signal-to-noise ratio. Using an acousto-optic deflector to generate a "time-shared" dual-optical trap, we decreased low-frequency noise by more than one order of magnitude compared with conventional dual-trap optical tweezers. Using this instrument, we implemented a protocol that synthesizes single base-pair trajectories, which are used to test a Large State Space Hidden Markov Model algorithm to recover their individual steps. We then used this algorithm on real transcription data obtained in the same instrument to fully uncover the molecular trajectories of Escherichia coli RNA polymerase. We applied this procedure to reveal the effect of pyrophosphate on the distribution of dwell times between consecutive polymerase steps.}, } @article {pmid29351993, year = {2018}, author = {Suo, L and Xue, W and Gobet, M and Greenbaum, SG and Wang, C and Chen, Y and Yang, W and Li, Y and Li, J}, title = {Fluorine-donating electrolytes enable highly reversible 5-V-class Li metal batteries.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1156-1161}, pmid = {29351993}, issn = {1091-6490}, support = {G12 MD007599/MD/NIMHD NIH HHS/United States ; }, mesh = {*Electric Power Supplies ; Electrodes ; Electrolytes/*chemistry ; Fluorine/*chemistry ; *Lithium ; Oxidation-Reduction ; Photoelectron Spectroscopy ; }, abstract = {Lithium metal has gravimetric capacity ∼10× that of graphite which incentivizes rechargeable Li metal batteries (RLMB) development. A key factor that limits practical use of RLMB is morphological instability of Li metal anode upon electrodeposition, reflected by the uncontrolled area growth of solid-electrolyte interphase that traps cyclable Li, quantified by the Coulombic inefficiency (CI). Here we show that CI decreases approximately exponentially with increasing donatable fluorine concentration of the electrolyte. By using up to 7 m of Li bis(fluorosulfonyl)imide in fluoroethylene carbonate, where both the solvent and the salt donate F, we can significantly suppress anode porosity and improve the Coulombic efficiency to 99.64%. The electrolyte demonstrates excellent compatibility with 5-V LiNi0.5Mn1.5O4 cathode and Al current collector beyond 5 V. As a result, an RLMB full cell with only 1.4× excess lithium as the anode was demonstrated to cycle above 130 times, at industrially significant loading of 1.83 mAh/cm2 and 0.36 C. This is attributed to the formation of a protective LiF nanolayer, which has a wide bandgap, high surface energy, and small Burgers vector, making it ductile at room temperature and less likely to rupture in electrodeposition.}, } @article {pmid29351992, year = {2018}, author = {Shackleford, G and Sampathkumar, NK and Hichor, M and Weill, L and Meffre, D and Juricek, L and Laurendeau, I and Chevallier, A and Ortonne, N and Larousserie, F and Herbin, M and Bièche, I and Coumoul, X and Beraneck, M and Baulieu, EE and Charbonnier, F and Pasmant, E and Massaad, C}, title = {Involvement of Aryl hydrocarbon receptor in myelination and in human nerve sheath tumorigenesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1319-E1328}, pmid = {29351992}, issn = {1091-6490}, mesh = {Animals ; Apoptosis ; Basic Helix-Loop-Helix Transcription Factors/*physiology ; Cell Transformation, Neoplastic/genetics/metabolism/*pathology ; Cells, Cultured ; *Gene Expression Regulation, Neoplastic ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Myelin Sheath/metabolism/*pathology ; Nerve Sheath Neoplasms/genetics/metabolism/*pathology ; Receptors, Aryl Hydrocarbon/*physiology ; Signal Transduction ; }, abstract = {Aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor involved in xenobiotic metabolism. Plexiform neurofibromas (PNFs) can transform into malignant peripheral nerve sheath tumors (MPNSTs) that are resistant to existing therapies. These tumors are primarily composed of Schwann cells. In addition to neurofibromatosis type 1 (NF1) gene inactivation, further genetic lesions are required for malignant transformation. We have quantified the mRNA expression levels of AHR and its associated genes in 38 human samples. We report that AHR and the biosynthetic enzymes of its endogenous ligand are overexpressed in human biopsies of PNFs and MPNSTs. We also detect a strong nuclear AHR staining in MPNSTs. The inhibition of AHR by siRNA or antagonists, CH-223191 and trimethoxyflavone, induces apoptosis in human MPNST cells. Since AHR dysregulation is observed in these tumors, we investigate AHR involvement in Schwann cell physiology. Hence, we studied the role of AHR in myelin structure and myelin gene regulation in Ahr-/- mice during myelin development. AHR ablation leads to locomotion defects and provokes thinner myelin sheaths around the axons. We observe a dysregulation of myelin gene expression and myelin developmental markers in Ahr-/- mice. Interestingly, AHR does not directly bind to myelin gene promoters. The inhibition of AHR in vitro and in vivo increased β-catenin levels and stimulated the binding of β-catenin on myelin gene promoters. Taken together, our findings reveal an endogenous role of AHR in peripheral myelination and in peripheral nerve sheath tumors. Finally, we suggest a potential therapeutic approach by targeting AHR in nerve tumors.}, } @article {pmid29351991, year = {2018}, author = {Sundararaj, S and Zhang, J and Krovi, SH and Bedel, R and Tuttle, KD and Veerapen, N and Besra, GS and Khandokar, Y and Praveena, T and Le Nours, J and Matsuda, JL and Rossjohn, J and Gapin, L}, title = {Differing roles of CD1d2 and CD1d1 proteins in type I natural killer T cell development and function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1204-E1213}, pmid = {29351991}, issn = {1091-6490}, support = {P30 CA046934/CA/NCI NIH HHS/United States ; R21 AI121761/AI/NIAID NIH HHS/United States ; R21 AI124076/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antigen Presentation/*immunology ; Antigens, CD1d/*physiology ; *Cell Differentiation ; Cells, Cultured ; Crystallography, X-Ray ; Glycolipids/*immunology ; Killer Cells, Natural/cytology/*immunology ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Protein Conformation ; Protein Isoforms ; Thymus Gland/cytology/*immunology ; }, abstract = {MHC class I-like CD1 molecules have evolved to present lipid-based antigens to T cells. Differences in the antigen-binding clefts of the CD1 family members determine the conformation and size of the lipids that are presented, although the factors that shape CD1 diversity remain unclear. In mice, two homologous genes, CD1D1 and CD1D2, encode the CD1d protein, which is essential to the development and function of natural killer T (NKT) cells. However, it remains unclear whether both CD1d isoforms are equivalent in their antigen presentation capacity and functions. Here, we report that CD1d2 molecules are expressed in the thymus of some mouse strains, where they select functional type I NKT cells. Intriguingly, the T cell antigen receptor repertoire and phenotype of CD1d2-selected type I NKT cells in CD1D1-/- mice differed from CD1d1-selected type I NKT cells. The structures of CD1d2 in complex with endogenous lipids and a truncated acyl-chain analog of α-galactosylceramide revealed that its A'-pocket was restricted in size compared with CD1d1. Accordingly, CD1d2 molecules could not present glycolipid antigens with long acyl chains efficiently, favoring the presentation of short acyl chain antigens. These results indicate that the two CD1d molecules present different sets of self-antigen(s) in the mouse thymus, thereby impacting the development of invariant NKT cells.}, } @article {pmid29351990, year = {2018}, author = {Djurec, M and Graña, O and Lee, A and Troulé, K and Espinet, E and Cabras, L and Navas, C and Blasco, MT and Martín-Díaz, L and Burdiel, M and Li, J and Liu, Z and Vallespinós, M and Sanchez-Bueno, F and Sprick, MR and Trumpp, A and Sainz, B and Al-Shahrour, F and Rabadan, R and Guerra, C and Barbacid, M}, title = {Saa3 is a key mediator of the protumorigenic properties of cancer-associated fibroblasts in pancreatic tumors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1147-E1156}, pmid = {29351990}, issn = {1091-6490}, support = {250297//European Research Council/International ; }, mesh = {Animals ; Cancer-Associated Fibroblasts/metabolism/*pathology ; Carcinoma, Pancreatic Ductal/genetics/metabolism/*pathology ; Cell Movement ; Cell Proliferation ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Pancreas/metabolism/*pathology ; Pancreatic Neoplasms/genetics/metabolism/*pathology ; Serum Amyloid A Protein/genetics/*metabolism/*physiology ; Stromal Cells/metabolism/*pathology ; Tumor Microenvironment ; }, abstract = {Pancreatic ductal adenocarcinoma (PDAC) is characterized by the presence of abundant desmoplastic stroma primarily composed of cancer-associated fibroblasts (CAFs). It is generally accepted that CAFs stimulate tumor progression and might be implicated in drug resistance and immunosuppression. Here, we have compared the transcriptional profile of PDGFRα+ CAFs isolated from genetically engineered mouse PDAC tumors with that of normal pancreatic fibroblasts to identify genes potentially implicated in their protumorigenic properties. We report that the most differentially expressed gene, Saa3, a member of the serum amyloid A (SAA) apolipoprotein family, is a key mediator of the protumorigenic activity of PDGFRα+ CAFs. Whereas Saa3-competent CAFs stimulate the growth of tumor cells in an orthotopic model, Saa3-null CAFs inhibit tumor growth. Saa3 also plays a role in the cross talk between CAFs and tumor cells. Ablation of Saa3 in pancreatic tumor cells makes them insensitive to the inhibitory effect of Saa3-null CAFs. As a consequence, germline ablation of Saa3 does not prevent PDAC development in mice. The protumorigenic activity of Saa3 in CAFs is mediated by Mpp6, a member of the palmitoylated membrane protein subfamily of the peripheral membrane-associated guanylate kinases (MAGUK). Finally, we interrogated whether these observations could be translated to a human scenario. Indeed, SAA1, the ortholog of murine Saa3, is overexpressed in human CAFs. Moreover, high levels of SAA1 in the stromal component correlate with worse survival. These findings support the concept that selective inhibition of SAA1 in CAFs may provide potential therapeutic benefit to PDAC patients.}, } @article {pmid29351989, year = {2018}, author = {Basu, S and Kumbier, K and Brown, JB and Yu, B}, title = {Iterative random forests to discover predictive and stable high-order interactions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1943-1948}, pmid = {29351989}, issn = {1091-6490}, support = {R00 HG006698/HG/NHGRI NIH HHS/United States ; T32 LM012417/LM/NLM NIH HHS/United States ; U01 HG007031/HG/NHGRI NIH HHS/United States ; }, mesh = {Algorithms ; Alternative Splicing ; Animals ; Computational Biology ; Drosophila/*genetics ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Genome-Wide Association Study ; *Models, Genetic ; }, abstract = {Genomics has revolutionized biology, enabling the interrogation of whole transcriptomes, genome-wide binding sites for proteins, and many other molecular processes. However, individual genomic assays measure elements that interact in vivo as components of larger molecular machines. Understanding how these high-order interactions drive gene expression presents a substantial statistical challenge. Building on random forests (RFs) and random intersection trees (RITs) and through extensive, biologically inspired simulations, we developed the iterative random forest algorithm (iRF). iRF trains a feature-weighted ensemble of decision trees to detect stable, high-order interactions with the same order of computational cost as the RF. We demonstrate the utility of iRF for high-order interaction discovery in two prediction problems: enhancer activity in the early Drosophila embryo and alternative splicing of primary transcripts in human-derived cell lines. In Drosophila, among the 20 pairwise transcription factor interactions iRF identifies as stable (returned in more than half of bootstrap replicates), 80% have been previously reported as physical interactions. Moreover, third-order interactions, e.g., between Zelda (Zld), Giant (Gt), and Twist (Twi), suggest high-order relationships that are candidates for follow-up experiments. In human-derived cells, iRF rediscovered a central role of H3K36me3 in chromatin-mediated splicing regulation and identified interesting fifth- and sixth-order interactions, indicative of multivalent nucleosomes with specific roles in splicing regulation. By decoupling the order of interactions from the computational cost of identification, iRF opens additional avenues of inquiry into the molecular mechanisms underlying genome biology.}, } @article {pmid29351988, year = {2018}, author = {Sahasrabuddhe, A and Hsia, Y and Busch, F and Sheffler, W and King, NP and Baker, D and Wysocki, VH}, title = {Confirmation of intersubunit connectivity and topology of designed protein complexes by native MS.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1268-1273}, pmid = {29351988}, issn = {1091-6490}, support = {R01 GM113658/GM/NIGMS NIH HHS/United States ; }, mesh = {Avidin/chemistry ; Lactoglobulins/chemistry ; Mass Spectrometry/*methods ; Models, Molecular ; Multiprotein Complexes/*chemistry/metabolism ; Prealbumin/chemistry ; Protein Engineering/methods ; Protein Interaction Domains and Motifs ; Recombinant Proteins/chemistry ; }, abstract = {Computational protein design provides the tools to expand the diversity of protein complexes beyond those found in nature. Understanding the rules that drive proteins to interact with each other enables the design of protein-protein interactions to generate specific protein assemblies. In this work, we designed protein-protein interfaces between dimers and trimers to generate dodecameric protein assemblies with dihedral point group symmetry. We subsequently analyzed the designed protein complexes by native MS. We show that the use of ion mobility MS in combination with surface-induced dissociation (SID) allows for the rapid determination of the stoichiometry and topology of designed complexes. The information collected along with the speed of data acquisition and processing make SID ion mobility MS well-suited to determine key structural features of designed protein complexes, thereby circumventing the requirement for more time- and sample-consuming structural biology approaches.}, } @article {pmid29351813, year = {2018}, author = {Liu, T and Zhang, AN and Wang, J and Liu, S and Jiang, X and Dang, C and Ma, T and Liu, S and Chen, Q and Xie, S and Zhang, T and Ni, J}, title = {Integrated biogeography of planktonic and sedimentary bacterial communities in the Yangtze River.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {16}, pmid = {29351813}, issn = {2049-2618}, support = {No.51721006 and 91647211//National Natural Science Foundation of China (CN)/International ; }, mesh = {Asia ; Bacteria/*classification/genetics/isolation & purification ; Ecosystem ; Environmental Monitoring ; Geologic Sediments/*microbiology ; Phylogeny ; Phylogeography ; Plankton/*microbiology ; RNA, Ribosomal, 16S/*genetics ; Rivers/microbiology ; Seasons ; Sequence Analysis, DNA/*methods ; Water Microbiology ; }, abstract = {BACKGROUND: Bacterial communities are essential to the biogeochemical cycle in riverine ecosystems. However, little is presently known about the integrated biogeography of planktonic and sedimentary bacterial communities in large rivers.

RESULTS: This study provides the first spatiotemporal pattern of bacterial communities in the Yangtze River, the largest river in Asia with a catchment area of 1,800,000 km2. We find that sedimentary bacteria made larger contributions than planktonic bacteria to the bacterial diversity of the Yangzte River ecosystem with the sediment subgroup providing 98.8% of 38,906 operational taxonomic units (OTUs) observed in 280 samples of synchronous flowing water and sediment at 50 national monitoring stations covering a 4300 km reach. OTUs within the same phylum displayed uniform seasonal variations, and many phyla demonstrated autumn preference throughout the length of the river. Seasonal differences in bacterial communities were statistically significant in water, whereas bacterial communities in both water and sediment were geographically clustered according to five types of landforms: mountain, foothill, basin, foothill-mountain, and plain. Interestingly, the presence of two huge dams resulted in a drastic fall of bacterial taxa in sediment immediately downstream due to severe riverbed scouring. The integrity of the biogeography is satisfactorily interpreted by the combination of neutral and species sorting perspectives in meta-community theory for bacterial communities in flowing water and sediment.

CONCLUSIONS: Our study fills a gap in understanding of bacterial communities in one of the world's largest river and highlights the importance of both planktonic and sedimentary communities to the integrity of bacterial biogeographic patterns in a river subject to varying natural and anthropogenic impacts.}, } @article {pmid29351808, year = {2018}, author = {Hashmi, AA and Hashmi, SK and Ali, N and Thara, K and Ali, R and Edhi, MM and Faridi, N and Khan, A}, title = {Clinicopathologic features of colorectal carcinoma: features predicting higher T-stage and nodal metastasis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {52}, pmid = {29351808}, issn = {1756-0500}, mesh = {Adenocarcinoma/genetics/*pathology ; Adenocarcinoma, Mucinous/genetics/*pathology ; Adult ; Aged ; Aged, 80 and over ; Colorectal Neoplasms/genetics/*pathology ; Female ; Humans ; Lymphatic Metastasis ; Male ; Microsatellite Instability ; Middle Aged ; Neoplasm Staging ; Pakistan ; Prognosis ; Young Adult ; }, abstract = {OBJECTIVES: A rising frequency of colorectal carcinoma has been noted in recent years in Pakistan. In the present study, we aimed to evaluate clinicopathologic features of colorectal carcinoma in our population so that protocols could be developed to stratify patients that may require further biomarker/molecular testing. Furthermore, histological features which predict higher T and N stage were also evaluated.

RESULTS: Median age at diagnosis was 54.5 (19-85) years. 79% cases were of conventional adenocarcinoma while 13% cases were of mucinous carcinoma. Most of the cases were at T3 stage (81%), while 27 and 68% of cases revealed lymphovascular invasion and nodal metastasis respectively. Mucinous and signet ring tumors were associated with a higher N stage. Pre-existing polyp was associated with lower T and N stage. We found a high proportion of our cases to present at advanced T-stage. Tumor grade and lymphovascular invasion were found to be associated with higher N-stage while tumor infiltrating lymphocytes was associated with lower T and N-stage. Moreover, a high frequency of mucinous differentiation may be linked to microsatellite instability in our cases of colorectal carcinoma; therefore, we suggest that microsatellite instability testing in colorectal carcinoma should be evaluated in our setup.}, } @article {pmid29351807, year = {2018}, author = {Björkhem-Bergman, L and Lehtihet, M and Rane, A and Ekström, L}, title = {Vitamin D receptor rs2228570 polymorphism is associated with LH levels in men exposed to anabolic androgenic steroids.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {51}, pmid = {29351807}, issn = {1756-0500}, mesh = {Adult ; Anabolic Agents/administration & dosage ; Cohort Studies ; Follicle Stimulating Hormone/blood ; Gene Frequency ; Genotype ; Humans ; Linkage Disequilibrium ; Luteinizing Hormone/*blood ; Male ; Pilot Projects ; *Polymorphism, Single Nucleotide ; Receptors, Calcitriol/*genetics ; Testosterone Congeners/*administration & dosage ; }, abstract = {OBJECTIVE: The primary aim of this study was to investigate the association between the vitamin D receptor polymorphisms rs2228570 (Fok1) and rs731236 (TaqI) and LH and FSH levels in relation to anabolic androgenic steroid (AAS) use.

RESULTS: Two cohorts were analyzed. Cohort 1 comprised healthy volunteers given single supra-physiological doses of 500 mg testosterone (n = 25). Cohort 2 comprised 45 self-reporting AAS users. Healthy volunteers homozygous for the C-allele of the Fok1 polymorphism exhibited 30% higher LH levels than T-carriers at baseline (p = 0.04) and twice the levels 14 days after testosterone administration (p = 0.01). AAS users homozygous for the C-allele had four times higher LH levels than TT-individuals (p < 0.05). FSH levels were not associated with Fok1 polymorphism, nor were LH and FSH levels associated with the TaqI polymorphism. In conclusion, there is an association between LH levels and the Fok1 VDR polymorphism and this difference is even more pronounced in AAS users and subjects with suppressed LH levels.}, } @article {pmid29351806, year = {2018}, author = {Weerasinghe, NP and Herath, HMM and Liyanage, TMU}, title = {Isolated septic arthritis of hip joint: a rare presentation of melioidosis. A case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {50}, pmid = {29351806}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/therapeutic use ; Arthritis, Infectious/*diagnosis/drug therapy/microbiology ; Burkholderia pseudomallei/drug effects/isolation & purification ; Doxycycline/therapeutic use ; Female ; Hip Joint/drug effects/microbiology/*pathology ; Humans ; Imipenem/therapeutic use ; Melioidosis/*diagnosis/drug therapy/microbiology ; Middle Aged ; Sri Lanka ; Trimethoprim, Sulfamethoxazole Drug Combination/therapeutic use ; }, abstract = {BACKGROUND: Despite, Sri Lanka lies in the melioidosis endemic belt between 5°N and 10°N surrounded by countries known to have endemic melioidosis for many years, comparatively fewer cases of melioidosis infection have been reported in Sri Lanka. Melioidosis has a wide spectrum of clinical presentation, ranging from severe pneumonia to abscess formation in various organs. Isolated septic arthritis, which is a rare but well-recognized manifestation of melioidosis, could be the sole presenting problem in some patients with melioidosis.

CASE PRESENTATION: We report a middle aged diabetic female who has been on azathioprine for autoimmune hepatitis, presenting with pain and swelling of left hip joint. Investigations confirmed the clinical suspicion of septic arthritis, but all relevant microbiological investigations failed to isolate a causative organism. Due to the history of diabetes, possible immunosuppression with azathioprine, and failure to recognise the possible causative organism by initial investigations prompted us to investigate for melioidosis. Diagnosis of melioidosis was made by presence high titre of antibodies to melioidin antigen, and rapid response to appropriate treatment. The patient was treated with intravenous imipenem 1000 mg 6 hourly and oral cotrimoxazole (1920 mg 12 hourly) for 4 weeks followed by eradication therapy with cotrimoxazole and doxycycline.

CONCLUSION: Given that melioidosis-induced septic arthritis share common features with septic arthritis due to other common pyogenic bacteria, differentiation of these two conditions is extremely difficult. Therefore, melioidosis needs to be considered as a possibility, when a patient with risk factors for melioidosis such as diabetes or immunosuppression presents with isolated septic arthritis. This case report has been presented to raise the awareness of an unusual presentation of melioidosis; isolated septic arthritis.}, } @article {pmid29351805, year = {2018}, author = {Chen, B and Li, J and Borgens, RB}, title = {Neuroprotection by chitosan nanoparticles in oxidative stress-mediated injury.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {49}, pmid = {29351805}, issn = {1756-0500}, mesh = {Animals ; Apoptosis/drug effects/*physiology ; Cell Death/drug effects/physiology ; Cell Line ; Cell Proliferation/drug effects ; Chitosan/administration & dosage/*chemistry ; Hydrogen Peroxide/pharmacology ; Mice ; Microscopy, Electron, Transmission ; Nanoparticles/administration & dosage/*chemistry/ultrastructure ; Necrosis ; Neuroprotection/drug effects ; Oxidants/pharmacology ; Oxidative Stress/drug effects/*physiology ; }, abstract = {OBJECTIVE: Oxidative stress is a critical component of nervous system secondary injury. Oxidative stress produces toxic chemical byproducts including reactive aldehydes that traverse intact membranes and attack neighboring healthy cells. This secondary damage often leads to further patho-biochemical cascades that exacerbate the original insult. In this work, we investigate the therapeutic effects of chitosan nanoparticles on cell cultures exposed to oxidative stress.

RESULTS: We found chitosan nanoparticles can rescue BV-2 glial cells from death, but only for cells undergoing necrosis. Necrosis occurred when cultures were challenged with high concentrations of H2O2 (> 110 μM) whereas a slow and progressive loss of cultures was observed in more dilute (50-100 μM) peroxide applications. In the latter case, the primary mode of cell death was apoptosis. These studies revealed that while rescue of H2O2 challenged cultures was achieved for necrotic cell death, no such sparing was observed in apoptotic cells. Based on the current and cumulative data regarding the membrane fusogenic properties of chitosan, we conclude that chitosan neuroprotection arises from its membrane sealing effects. Consistent with this hypothesis is the observation that apoptotic cells did not exhibit early stage membrane damage. These in vitro results elucidate mechanisms by which membrane fusogens may provide therapeutic benefit.}, } @article {pmid29351743, year = {2018}, author = {Vuppada, RK and Hansen, CR and Strickland, KAP and Kelly, KM and McCleary, WR}, title = {Phosphate signaling through alternate conformations of the PstSCAB phosphate transporter.}, journal = {BMC microbiology}, volume = {18}, number = {1}, pages = {8}, pmid = {29351743}, issn = {1471-2180}, support = {R15 GM096222/GM/NIGMS NIH HHS/United States ; R15GM96222//U.S. Public Health Service/International ; }, mesh = {Alkaline Phosphatase/analysis/metabolism ; Amino Acid Sequence ; Bacterial Proteins/genetics/metabolism ; Escherichia coli/*genetics/*metabolism ; Escherichia coli Proteins/genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial/genetics ; Histidine Kinase/genetics/metabolism ; Homeostasis/genetics/physiology ; Membrane Transport Proteins/genetics/metabolism ; Mutation ; Phosphate Transport Proteins/*metabolism ; Phosphates/*metabolism ; Protein Kinases ; Sequence Alignment ; Signal Transduction/*genetics ; Starvation ; Transcription Factors/genetics/metabolism ; }, abstract = {BACKGROUND: Phosphate is an essential compound for life. Escherichia coli employs a signal transduction pathway that controls the expression of genes that are required for the high-affinity acquisition of phosphate and the utilization of alternate sources of phosphorous. These genes are only expressed when environmental phosphate is limiting. The seven genes for this signaling pathway encode the two-component regulatory proteins PhoB and PhoR, as well as the high-affinity phosphate transporter PstSCAB and an auxiliary protein called PhoU. As the sensor kinase PhoR has no periplasmic sensory domain, the mechanism by which these cells sense environmental phosphate is not known. This paper explores the hypothesis that it is the alternating conformations of the PstSCAB transporter which are formed as part of the normal phosphate transport cycle that signal phosphate sufficiency or phosphate limitation.

RESULTS: We tested two variants of PstB that are predicted to lock the protein in either of two conformations for their signaling output. We observed that the pstBQ160K mutant, predicted to reside in an inward-facing, open conformation signaled phosphate sufficiency whereas the pstBE179Q mutant, predicted to reside in an outward-facing, closed conformation signaled phosphate starvation. Neither mutant showed phosphate transport.

CONCLUSIONS: These results support the hypothesis that the alternating conformations of the PstSCAB transporter are sensed by PhoR and PhoU. This sensory mechanism thus controls the alternate autokinase and phospho-PhoB phosphatase activities of PhoR, which ultimately control the signaling state of the response regulator PhoB.}, } @article {pmid29351742, year = {2018}, author = {Grandi, N and Cadeddu, M and Blomberg, J and Mayer, J and Tramontano, E}, title = {HERV-W group evolutionary history in non-human primates: characterization of ERV-W orthologs in Catarrhini and related ERV groups in Platyrrhini.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {6}, pmid = {29351742}, issn = {1471-2148}, mesh = {Animals ; Base Sequence ; *Biological Evolution ; Catarrhini/*virology ; Endogenous Retroviruses/*genetics ; Evolution, Molecular ; Genome ; Humans ; Phylogeny ; Platyrrhini/*virology ; *Sequence Homology, Nucleic Acid ; Species Specificity ; }, abstract = {BACKGROUND: The genomes of all vertebrates harbor remnants of ancient retroviral infections, having affected the germ line cells during the last 100 million years. These sequences, named Endogenous Retroviruses (ERVs), have been transmitted to the offspring in a Mendelian way, being relatively stable components of the host genome even long after their exogenous counterparts went extinct. Among human ERVs (HERVs), the HERV-W group is of particular interest for our physiology and pathology. A HERV-W provirus in locus 7q21.2 has been coopted during evolution to exert an essential role in placenta, and the group expression has been tentatively linked to Multiple Sclerosis and other diseases. Following up on a detailed analysis of 213 HERV-W insertions in the human genome, we now investigated the ERV-W group genomic spread within primate lineages.

RESULTS: We analyzed HERV-W orthologous loci in the genome sequences of 12 non-human primate species belonging to Simiiformes (parvorders Catarrhini and Platyrrhini), Tarsiiformes and to the most primitive Prosimians. Analysis of HERV-W orthologous loci in non-human Catarrhini primates revealed species-specific insertions in the genomes of Chimpanzee (3), Gorilla (4), Orangutan (6), Gibbon (2) and especially Rhesus Macaque (66). Such sequences were acquired in a retroviral fashion and, in the majority of cases, by L1-mediated formation of processed pseudogenes. There were also a number of LTR-LTR homologous recombination events that occurred subsequent to separation of Catarrhini sub-lineages. Moreover, we retrieved 130 sequences in Marmoset and Squirrel Monkeys (family Cebidae, Platyrrhini parvorder), identified as ERV1-1_CJa based on RepBase annotations, which appear closely related to the ERV-W group. Such sequences were also identified in Atelidae and Pitheciidae, representative of the other Platyrrhini families. In contrast, no ERV-W-related sequences were found in genome sequence assemblies of Tarsiiformes and Prosimians.

CONCLUSIONS: Overall, our analysis now provides a detailed picture of the ERV-W sequences colonization of the primate lineages genomes, revealing the exact dynamics of ERV-W locus formations as well as novel insights into the evolution and origin of the group.}, } @article {pmid29351740, year = {2018}, author = {Chen, J and Ni, P and Li, X and Han, J and Jakovlić, I and Zhang, C and Zhao, S}, title = {Population size may shape the accumulation of functional mutations following domestication.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {4}, pmid = {29351740}, issn = {1471-2148}, support = {31361140365//NSFC-CGIAR Cooperation project/International ; 863 Program, 2013AA102502 to SZ//National High Technology Research and Development Program of China/International ; }, mesh = {Animals ; Animals, Domestic/*genetics ; Animals, Wild/genetics ; *Domestication ; Evolution, Molecular ; Mutation/*genetics ; Phenotype ; *Population Density ; Selection, Genetic ; Species Specificity ; }, abstract = {BACKGROUND: Population genetics theory predicts an important role of differences in the effective population size (N e) among species on shaping the accumulation of functional mutations by regulating the selection efficiency. However, this correlation has never been tested in domesticated animals.

RESULTS: Here, we synthesized 62 whole genome data in eight domesticated species (cat, dog, pig, goat, sheep, chicken, cattle and horse) and compared domesticates with their wild (or ancient) relatives. Genes with significantly different selection pressures (revealed by nonsynonymous/synonymous substitution rate ratios, Ka/Ks or ω) between domesticated (Dω) and wild animals (Wω) were determined by likelihood-ratio tests. Species-level effective population sizes (N e) were evaluated by the pairwise sequentially Markovian coalescent (PSMC) model, and Dω/Wω were calculated for each species to evaluate the changes in accumulation of functional mutations after domestication relative to pre-domestication period. Correlation analysis revealed that the most recent (~ 10.000 years ago) N e (s) are positively correlated with Dω/Wω. This result is consistent with the corollary of the nearly neutral theory, that higher N e could boost the efficiency of positive selection, which might facilitate the overall accumulation of functional mutations. In addition, we also evaluated the accumulation of radical and conservative mutations during the domestication transition as: Dradical/Wradical and Dconservative/Wconservative, respectively. Surprisingly, only Dradical/Wradical ratio exhibited a positive correlation with N e (p < 0.05), suggesting that domestication process might magnify the accumulation of radical mutations in species with larger N e .

CONCLUSIONS: Our results confirm the classical population genetics theory prediction and highlight the important role of species' N e in shaping the patterns of accumulation of functional mutations, especially radical mutations, in domesticated animals. The results aid our understanding of the mechanisms underlying the accumulation of functional mutations after domestication, which is critical for understanding the phenotypic diversification associated with this process.}, } @article {pmid29351737, year = {2018}, author = {Elbers, JP and Brown, MB and Taylor, SS}, title = {Identifying genome-wide immune gene variation underlying infectious disease in wildlife populations - a next generation sequencing approach in the gopher tortoise.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {64}, pmid = {29351737}, issn = {1471-2164}, support = {LAB04066//U.S. Department of Agriculture, McIntire Stennis/International ; K08 AI057722/AI/NIAID NIH HHS/United States ; P30 DK072476/DK/NIDDK NIH HHS/United States ; 5K08AI57722/NH/NIH HHS/United States ; LAB94169//U.S. Department of Agriculture, McIntire Stennis/International ; P20 GM103528/GM/NIGMS NIH HHS/United States ; DEB-0224953//Division of Environmental Biology/International ; 8P20GM103528/NH/NIH HHS/United States ; 2P30DK072476/NH/NIH HHS/United States ; }, mesh = {Animals ; Genetic Predisposition to Disease ; *Genetic Variation ; Genome-Wide Association Study ; High-Throughput Nucleotide Sequencing ; Immunogenetic Phenomena ; Mycoplasma Infections/genetics/veterinary ; Respiratory Tract Infections/genetics/veterinary ; Turtles/*genetics ; }, abstract = {BACKGROUND: Infectious disease is the single greatest threat to taxa such as amphibians (chytrid fungus), bats (white nose syndrome), Tasmanian devils (devil facial tumor disease), and black-footed ferrets (canine distemper virus, plague). Although understanding the genetic basis to disease susceptibility is important for the long-term persistence of these groups, most research has been limited to major-histocompatibility and Toll-like receptor genes. To better understand the genetic basis of infectious disease susceptibility in a species of conservation concern, we sequenced all known/predicted immune response genes (i.e., the immunomes) in 16 Florida gopher tortoises, Gopherus polyphemus. All tortoises produced antibodies against Mycoplasma agassizii (an etiologic agent of infectious upper respiratory tract disease; URTD) and, at the time of sampling, either had (n = 10) or lacked (n = 6) clinical signs.

RESULTS: We found several variants associated with URTD clinical status in complement and lectin genes, which may play a role in Mycoplasma immunity. Thirty-five genes deviated from neutrality according to Tajima's D. These genes were enriched in functions relating to macromolecule and protein modifications, which are vital to immune system functioning.

CONCLUSIONS: These results are suggestive of genetic differences that might contribute to disease severity, a finding that is consistent with other mycoplasmal diseases. This has implications for management because tortoises across their range may possess genetic variation associated with a more severe response to URTD. More generally: 1) this approach demonstrates that a broader consideration of immune genes is better able to identify important variants, and; 2) this data pipeline can be adopted to identify alleles associated with disease susceptibility or resistance in other taxa, and therefore provide information on a population's risk of succumbing to disease, inform translocations to increase genetic variation for disease resistance, and help to identify potential treatments.}, } @article {pmid29351734, year = {2018}, author = {Wang, RL and Miao, W and Wang, W and Xiong, J and Liang, AH}, title = {EOGD: the Euplotes octocarinatus genome database.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {63}, pmid = {29351734}, issn = {1471-2164}, support = {31372199//National Natural Science Foundation of China/International ; 31471999//National Natural Science Foundation of China/International ; 31372168//National Natural Science Foundation of China/International ; 31301930//Natural Science Foundation of China/International ; }, mesh = {*Databases, Genetic ; Euplotes/*genetics ; Gene Expression Profiling ; *Genome ; }, abstract = {BACKGROUND: Euplotes, a ciliated protozoan, is a useful unicellular model organism. Studies on Euplotes have provided excellent insights into various basic biological principles. We have recently sequenced the macronuclear genome of the common freshwater species Euplotes octocarinatus to provide novel insights into Euplotes genetics and molecular biology.

RESULTS: In this study, we present the E. octocarinatus Genome Database (EOGD), a functional annotation and analysis platform for the global study of the Euplotes genome. EOGD includes macronuclear genomic and transcriptomic data, predicted gene models, coding sequences, protein sequences, and functional annotations. The GBrowser and BLAST tools are embedded in EOGD to enable the search, visualization and analysis of E. octocarinatus genomic and transcriptomic data.

CONCLUSIONS: EOGD is a useful resource for the research community, particularly for researchers who conduct genome-scale analysis and molecular biology studies of Euplotes or other ciliates. EOGD will be continuously updated to integrate more datasets and analytical tools. EOGD is freely available at http://ciliates.ihb.ac.cn/database/home/#eo .}, } @article {pmid29351733, year = {2018}, author = {García-Gutiérrez, Á and Cánovas, FM and Ávila, C}, title = {Glutamate synthases from conifers: gene structure and phylogenetic studies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {65}, pmid = {29351733}, issn = {1471-2164}, support = {PLE2009-0016//Plant KBBE program/International ; FP7-KBBE-289841//FP7-KBBE/International ; BIO2015-69285-R//Spanish Ministerio de Economía y Competitividad/International ; BIO-474//Consejería de Economía, Innovación, Ciencia y Empleo, Junta de Andalucía/International ; }, mesh = {Coniferophyta/*enzymology/*genetics ; Exons ; Gene Dosage ; Genes, Plant ; Genome, Plant ; Glutamate Synthase/chemistry/classification/*genetics ; Introns ; Phylogeny ; Plant Proteins/chemistry/classification/*genetics ; Protein Domains ; Retroelements ; }, abstract = {BACKGROUND: Plants synthesize glutamate from ammonium by the combined activity of the enzymes glutamine synthetase (GS) and glutamate synthase (GOGAT) through the glutamate synthase cycle. In plants, there are two forms of glutamate synthases that differ in their electron donors, NADH-GOGAT (EC 1.4.1.14) and Fd-GOGAT (EC 1.4.7.1), which have differential roles either in primary ammonia assimilation or in the reassimilation of ammonium from different catabolic processes. Glutamate synthases are complex iron-sulfur flavoproteins containing functional domains involved in the control and coordination of their catalytic activities in annual plants. In conifers, partial cDNA sequences for GOGATs have been isolated and used for gene expression studies. However, knowledge of the gene structure and of phylogenetic relationships with other plant enzymes is quite scant.

RESULTS: Technological advances in conifer megagenomes sequencing have made it possible to obtain full-length cDNA sequences encoding Fd- and NADH-GOGAT from maritime pine, as well as BAC clones containing sequences for NADH-GOGAT and Fd-GOGAT genes. In the current study, we studied the genomic organization of pine GOGAT genes, the size of their exons/introns, copy numbers in the pine genome and relationships with other plant genes. Phylogenetic analysis was performed, and the degree of preservation and dissimilarity of key domains for the catalytic activities of these enzymes in different taxa were determined.

CONCLUSIONS: Fd- and NADH-GOGAT are encoded by single-copy genes in the maritime pine genome. The Fd-GOGAT gene is extremely large spanning more than 330 kb and the presence of very long introns highlights the important contribution of LTR retrotransposons to the gene size in conifers. In contrast, the structure of the NADH-GOGAT gene is similar to the orthologous genes in angiosperms. Our phylogenetic analysis indicates that these two genes had different origins during plant evolution. The results provide new insights into the structure and molecular evolution of these essential genes.}, } @article {pmid29351732, year = {2018}, author = {Fleischmann, J and Rocha, MA}, title = {Nutrient depletion and TOR inhibition induce 18S and 25S ribosomal RNAs resistant to a 5'-phosphate-dependent exonuclease in Candida albicans and other yeasts.}, journal = {BMC molecular biology}, volume = {19}, number = {1}, pages = {1}, pmid = {29351732}, issn = {1471-2199}, mesh = {Alkaline Phosphatase/metabolism ; Candida albicans/genetics/*growth & development/metabolism ; Phosphodiesterase I/*metabolism ; Protein Kinase Inhibitors/*pharmacology ; Pyrophosphatases/metabolism ; RNA, Fungal/metabolism ; RNA, Ribosomal/*metabolism ; RNA, Ribosomal, 18S/*metabolism ; Sirolimus/pharmacology ; Stress, Physiological ; TOR Serine-Threonine Kinases/antagonists & inhibitors ; }, abstract = {BACKGROUND: Messenger RNA (mRNA) represents a small percentage of RNAs in a cell, with ribosomal RNA (rRNA) making up the bulk of it. To isolate mRNA from eukaryotes, typically poly-A selection is carried out. Recently, a 5´-phosphate-dependent, 5´→3´ processive exonuclease called Terminator has become available. It will digest only RNA that has a 5´-monophosphate end and therefore it is very useful to eliminate most of rRNAs in cell.

RESULTS: We have found that in the pathogenic yeast Candida albicans, while 18S and 25S components isolated from yeast in robust growth phase are easily eliminated by Terminator, those isolated from cells in the nutritionally diminished stationary phase, become resistant to digestion by this enzyme. Additional digestions with alkaline phosphatase, tobacco pyrophosphatase combined with Terminator point toward the 5'-prime end of 18S and 25S as the source of this resistance. Inhibition of TOR by rapamycin also induces resistance by these molecules. We also find that these molecules are incorporated into the ribosome and are not just produced incidentally. Finally, we show that three other yeasts show the same behavior.

CONCLUSIONS: Digestion of RNA by Terminator has revealed 18S and 25S rRNA molecules different from the accepted processed ones seen in ribosome generation. The reason for these molecules and the underlying mechanism for their formation is unknown. The preservation of this behavior across these yeasts suggests a useful biological role for it, worthy of further inquiry.}, } @article {pmid29351731, year = {2018}, author = {Cao, G and Shi, Y and Zhang, J and Ma, H and Hou, S and Dong, H and Hong, W and Chen, S and Li, H and Wu, Y and Guo, P and Shao, X and Xu, B and Shi, F and Meng, Y and Jin, Y}, title = {A chelicerate-specific burst of nonclassical Dscam diversity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {66}, pmid = {29351731}, issn = {1471-2164}, support = {31630089, 31430050, 91740104//the National Natural Science Foundation of China/International ; }, mesh = {Animals ; Arthropod Proteins/classification/*genetics/metabolism ; Arthropods/classification/*genetics/metabolism ; Cell Adhesion Molecules/classification/*genetics/metabolism ; Gene Expression ; Genes, Duplicate ; Genetic Variation ; Genome ; Phylogeny ; Protein Isoforms/genetics/metabolism ; }, abstract = {BACKGROUND: The immunoglobulin (Ig) superfamily receptor Down syndrome cell adhesion molecule (Dscam) gene can generate tens of thousands of isoforms via alternative splicing, which is essential for both nervous and immune systems in insects. However, further information is required to develop a comprehensive view of Dscam diversification across the broad spectrum of Chelicerata clades, a basal branch of arthropods and the second largest group of terrestrial animals.

RESULTS: In this study, a genome-wide comprehensive analysis of Dscam genes across Chelicerata species revealed a burst of nonclassical Dscams, categorised into four types-mDscam, sDscamα, sDscamβ, and sDscamγ-based on their size and structure. Although the mDscam gene class includes the highest number of Dscam genes, the sDscam genes utilise alternative promoters to expand protein diversity. Furthermore, we indicated that the 5' cassette duplicate is inversely correlated with the sDscam gene duplicate. We showed differential and sDscam- biased expression of nonclassical Dscam isoforms. Thus, the Dscam isoform repertoire across Chelicerata is entirely dominated by the number and expression levels of nonclassical Dscams. Taken together, these data show that Chelicerata evolved a large conserved and lineage-specific repertoire of nonclassical Dscams.

CONCLUSIONS: This study showed that arthropods have a large diversified Chelicerata-specific repertoire of nonclassical Dscam isoforms, which are structurally and mechanistically distinct from those of insects. These findings provide a global framework for the evolution of Dscam diversity in arthropods and offer mechanistic insights into the diversification of the clade-specific Ig superfamily repertoire.}, } @article {pmid29351730, year = {2018}, author = {Michalecka, M and Masny, S and Leroy, T and Puławska, J}, title = {Population structure of Venturia inaequalis, a causal agent of apple scab, in response to heterogeneous apple tree cultivation.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {5}, pmid = {29351730}, issn = {1471-2148}, support = {UMO-2013/09/B/NZ9/02343//Narodowe Centrum Nauki/International ; }, mesh = {Ascomycota/genetics/pathogenicity/*physiology ; Cluster Analysis ; Databases, Genetic ; Gene Frequency/genetics ; Genetic Variation ; Geography ; Haplotypes/genetics ; Malus/*growth & development/*microbiology ; Microsatellite Repeats/genetics ; Plant Diseases/*microbiology ; Poland ; Polymorphism, Genetic ; Principal Component Analysis ; Trees/*growth & development/*microbiology ; Virulence ; }, abstract = {BACKGROUND: Tracking newly emergent virulent populations in agroecosystems provides an opportunity to increase our understanding of the co-evolution dynamics of pathogens and their hosts. On the one hand host plants exert selective pressure on pathogen populations, thus dividing them into subpopulations of different virulence, while on the other hand they create an opportunity for secondary contact between the two divergent populations on one tree. The main objectives of the study were to explore whether the previously reported structure between two Venturia inaequalis population types, virulent or avirulent towards Malus x domestica cultivars carrying Rvi6 gene, is maintained or broken several years after the first emergence of new virulent strains in Poland, and to investigate the relationship between 'new' and 'native' populations derived from the same commercial orchards. For this purpose, we investigated the genetic structure of populations of the apple scab fungus, occurring on apple tree cultivars containing Rvi6, Rvi1 or Rvi17 resistance gene or no resistance at all, based on microsatellite data obtained from 606 strains sampled in 10 orchards composed of various host cultivars.

RESULTS: Application of genetic distance inferring and clustering methods allowed us to observe clear genetic distinctness of the populations virulent towards cultivars carrying Rvi6 gene from the Rvi6-avirulent populations and substructures within the Rvi6-group as a consequence of independent immigration events followed by rare, long-distance dispersals. We did not observe such a structuring effect of other genes determining apple scab resistance on any other populations, which in turn were genetically homogenous. However, in two orchards the co-occurrence of strains of different virulence pattern on the same trees was detected, blurring the genetic boundaries between populations.

CONCLUSIONS: Among several resistance genes studied, only Rvi6 exerted selective pressure on pathogens populations: those virulent toward Rvi6 hosts show unique and clear genetic and virulence pattern. For the first time in commercial Malus x domestica orchards, we reported secondary contacts between populations virulent and avirulent toward Rvi6 hosts. These two populations, first diverged in allopatry, second came into contact and subsequently began interbreeding, in such way that they show unambiguous footprints of gene flow today.}, } @article {pmid29351669, year = {2018}, author = {Figliuzzi, M and Barrat-Charlaix, P and Weigt, M}, title = {How Pairwise Coevolutionary Models Capture the Collective Residue Variability in Proteins?.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {1018-1027}, doi = {10.1093/molbev/msy007}, pmid = {29351669}, issn = {1537-1719}, abstract = {Global coevolutionary models of homologous protein families, as constructed by direct coupling analysis (DCA), have recently gained popularity in particular due to their capacity to accurately predict residue-residue contacts from sequence information alone, and thereby to facilitate tertiary and quaternary protein structure prediction. More recently, they have also been used to predict fitness effects of amino-acid substitutions in proteins, and to predict evolutionary conserved protein-protein interactions. These models are based on two currently unjustified hypotheses: 1) correlations in the amino-acid usage of different positions are resulting collectively from networks of direct couplings; and 2) pairwise couplings are sufficient to capture the amino-acid variability. Here, we propose a highly precise inference scheme based on Boltzmann-machine learning, which allows us to systematically address these hypotheses. We show how correlations are built up in a highly collective way by a large number of coupling paths, which are based on the proteins three-dimensional structure. We further find that pairwise coevolutionary models capture the collective residue variability across homologous proteins even for quantities which are not imposed by the inference procedure, like three-residue correlations, the clustered structure of protein families in sequence space or the sequence distances between homologs. These findings strongly suggest that pairwise coevolutionary models are actually sufficient to accurately capture the residue variability in homologous protein families.}, } @article {pmid29351633, year = {2018}, author = {Lindsey, ARI and Rice, DW and Bordenstein, SR and Brooks, AW and Bordenstein, SR and Newton, ILG}, title = {Evolutionary Genetics of Cytoplasmic Incompatibility Genes cifA and cifB in Prophage WO of Wolbachia.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {434-451}, pmid = {29351633}, issn = {1759-6653}, support = {P30 DK058404/DK/NIDDK NIH HHS/United States ; R01 AI132581/AI/NIAID NIH HHS/United States ; R21 HD086833/HD/NICHD NIH HHS/United States ; T32 GM080178/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Arthropods/*microbiology/physiology ; Evolution, Molecular ; *Genes, Viral ; Male ; Prophages/*genetics ; Reproduction ; Symbiosis ; Transcriptome ; Wolbachia/genetics/physiology/*virology ; }, abstract = {The bacterial endosymbiont Wolbachia manipulates arthropod reproduction to facilitate its maternal spread through host populations. The most common manipulation is cytoplasmic incompatibility (CI): Wolbachia-infected males produce modified sperm that cause embryonic mortality, unless rescued by embryos harboring the same Wolbachia. The genes underlying CI, cifA and cifB, were recently identified in the eukaryotic association module of Wolbachia's prophage WO. Here, we use transcriptomic and genomic approaches to address three important evolutionary facets of the cif genes. First, we assess whether or not cifA and cifB comprise a classic toxin-antitoxin operon in wMel and show that the two genes exhibit striking, transcriptional differences across host development. They can produce a bicistronic message despite a predicted hairpin termination element in their intergenic region. Second, cifA and cifB strongly coevolve across the diversity of phage WO. Third, we provide new domain and functional predictions across homologs within Wolbachia, and show that amino acid sequences vary substantially across the genus. Finally, we investigate conservation of cifA and cifB and find frequent degradation and loss of the genes in strains that no longer induce CI. Taken together, we demonstrate that cifA and cifB exhibit complex transcriptional regulation in wMel, provide functional annotations that broaden the potential mechanisms of CI induction, and report recurrent erosion of cifA and cifB in non-CI strains, thus expanding our understanding of the most widespread form of reproductive parasitism.}, } @article {pmid29351021, year = {2018}, author = {Butlin, RK and Smadja, CM}, title = {Coupling, Reinforcement, and Speciation.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {155-172}, doi = {10.1086/695136}, pmid = {29351021}, issn = {1537-5323}, abstract = {During the process of speciation, populations may diverge for traits and at their underlying loci that contribute barriers to gene flow. These barrier traits and barrier loci underlie individual barrier effects, by which we mean the contribution that a barrier locus or trait-or some combination of barrier loci or traits-makes to overall isolation. The evolution of strong reproductive isolation typically requires the origin of multiple barrier effects. Critically, it also requires the coincidence of barrier effects; for example, two barrier effects, one due to assortative mating and the other due to hybrid inviability, create a stronger overall barrier to gene flow if they coincide than if they distinguish independent pairs of populations. Here, we define "coupling" as any process that generates coincidence of barrier effects, resulting in a stronger overall barrier to gene flow. We argue that speciation research, both empirical and theoretical, needs to consider both the origin of barrier effects and the ways in which they are coupled. Coincidence of barrier effects can occur either as a by-product of selection on individual barrier effects or of population processes, or as an adaptive response to indirect selection. Adaptive coupling may be accompanied by further evolution that enhances individual barrier effects. Reinforcement, classically viewed as the evolution of prezygotic barriers to gene flow in response to costs of hybridization, is an example of this type of process. However, we argue for an extended view of reinforcement that includes coupling processes involving enhancement of any type of additional barrier effect as a result of an existing barrier. This view of coupling and reinforcement may help to guide development of both theoretical and empirical research on the process of speciation.}, } @article {pmid29351020, year = {2018}, author = {Pirotta, E and Mangel, M and Costa, DP and Mate, B and Goldbogen, JA and Palacios, DM and Hückstädt, LA and McHuron, EA and Schwarz, L and New, L}, title = {A Dynamic State Model of Migratory Behavior and Physiology to Assess the Consequences of Environmental Variation and Anthropogenic Disturbance on Marine Vertebrates.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {E40-E56}, doi = {10.1086/695135}, pmid = {29351020}, issn = {1537-5323}, abstract = {Integrating behavior and physiology is critical to formulating new hypotheses on the evolution of animal life-history strategies. Migratory capital breeders acquire most of the energy they need to sustain migration, gestation, and lactation before parturition. Therefore, when predicting the impact of environmental variation on such species, a mechanistic understanding of the physiology of their migratory behavior is required. Using baleen whales as a model system, we developed a dynamic state variable model that captures the interplay among behavioral decisions, energy, reproductive needs, and the environment. We applied the framework to blue whales (Balaenoptera musculus) in the eastern North Pacific Ocean and explored the effects of environmental and anthropogenic perturbations on female reproductive success. We demonstrate the emergence of migration to track prey resources, enabling us to quantify the trade-offs among capital breeding, body condition, and metabolic expenses. We predict that periodic climatic oscillations affect reproductive success less than unprecedented environmental changes do. The effect of localized, acute anthropogenic impacts depended on whales' behavioral response to the disturbance; chronic, but weaker, disturbances had little effect on reproductive success. Because we link behavior and vital rates by modeling individuals' energetic budgets, we provide a general framework to investigate the ecology of migration and assess the population consequences of disturbance, while identifying critical knowledge gaps.}, } @article {pmid29351019, year = {2018}, author = {Start, D}, title = {Keystone Individuals Alter Ecological and Evolutionary Consumer-Resource Dynamics.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {277-286}, doi = {10.1086/695322}, pmid = {29351019}, issn = {1537-5323}, abstract = {Intraspecific variation is central to our understanding of evolution and ecology, but these fields generally consider either the mean trait value or its variance. Alternatively, the keystone individual concept from behavioral ecology posits that a single individual with an extreme phenotype can have disproportionate and irreplaceable effects on group dynamics. Here, I generalize this concept to include nonbehavioral traits and broader ecological and evolutionary dynamics. I test for the effects of individuals with extreme phenotypes on the ecology and evolution of a gall-forming fly and its natural enemies that select for opposite gall sizes. Specifically, I introduce a putatively keystone predator-attracting individual gall-maker, hypothesizing that the presence of such an individual should (1) increase gall maker population-level mortality, (2) cause consumer communities to be dominated by species that are most attracted to the keystone individual, (3) increase selection for traits conferring defense against the most common consumer, and (4) weaken patterns of stabilizing selection. I find support for both the ecological and evolutionary consequences of single individuals with extreme phenotypes, suggesting that they can be considered keystone individuals. I discuss the generality of the keystone individual concept, suggesting likely consequences for ecology and evolution.}, } @article {pmid29351018, year = {2018}, author = {Kelstrup, HC and Hartfelder, K and Lopes, TF and Wossler, TC}, title = {The Behavior and Reproductive Physiology of a Solitary Progressive Provisioning Vespid Wasp: Evidence for a Solitary-Cycle Origin of Reproductive Castes.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {E27-E39}, doi = {10.1086/695336}, pmid = {29351018}, issn = {1537-5323}, abstract = {The emergence of queens and workers from solitary antecedents mark a major evolutionary transition in the history of life. The solitary progressive provisioning wasp Synagris cornuta, a member of the subfamily Eumeninae (basal to eusocial vespid wasps), alternates between behavioral states characterized as queenlike and worker-like. Akin to a queen in eusocial wasps, a S. cornuta female initiates construction of a cell into which she oviposits and then, similar to a worker, cares for the brood as it develops. The ovarian groundplan (OGP) hypothesis for caste origins predicts that these behavioral states are associated with cyclical changes in ovarian status, where females performing queenlike tasks have eggs and those performing worker-like tasks possess only small oocytes. Our findings show strong support for the OGP hypothesis: the ovaries of S. cornuta females undergo differential oogenesis depending on the behavioral phase: the largest oocyte in the ovaries of females building a cell progresses faster compared to that of females attending brood. Yet contrary to the OGP hypothesis, neither juvenile hormone nor ecdysteroids is associated with the reproductive cycle. Finally, the cuticular hydrocarbon profile showed no link with ovarian status, suggesting that fertility signals evolved subsequent to the emergence of group living.}, } @article {pmid29351017, year = {2018}, author = {Grainger, TN and Rego, AI and Gilbert, B}, title = {Temperature-Dependent Species Interactions Shape Priority Effects and the Persistence of Unequal Competitors.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {197-209}, doi = {10.1086/695688}, pmid = {29351017}, issn = {1537-5323}, abstract = {The order of species arrival at a site can determine the outcome of competitive interactions when early arrivers alter the environment or deplete shared resources. These priority effects are predicted to be stronger at high temperatures, as higher vital rates caused by warming allow early arrivers to more rapidly impact a shared environment. We tested this prediction using a pair of congeneric aphid species that specialize on milkweed plants. We manipulated temperature and arrival order of the two aphid species and measured aphid population dynamics and milkweed survival and defensive traits. We found that warming increased the impact of aphids on the quantity and quality of milkweed, which amplified the importance of priority effects by increasing the competitive exclusion of the inferior competitor when it arrived late. Warming also enhanced interspecific differences in dispersal, which could alter relative arrival times at a regional scale. Our experiment provides a first link between temperature-dependent trophic interactions, priority effects, and dispersal. This study suggests that the indirect and cascading effects of temperature observed here may be important determinants of diversity in the temporally and spatially complex landscapes that characterize ecological communities.}, } @article {pmid29351016, year = {2018}, author = {Wiens, JJ}, title = {Patterns of Local Community Composition Are Linked to Large-Scale Diversification and Dispersal of Clades.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {184-196}, doi = {10.1086/695495}, pmid = {29351016}, issn = {1537-5323}, abstract = {At any location, a group of organisms may be represented by several clades. What determines which clades will dominate local communities in terms of their species richness? Here, this relatively neglected question is addressed by analyzing 166 local assemblages of snakes distributed globally. For most regions, local assemblages are dominated by clades with higher global-scale diversification rates and more frequent dispersal into each region, and not by clades that have been present in that region longer. This result contrasts with many other studies of local richness (in other organisms), which show strong impacts of regional colonization time on overall local species richness of clades. Furthermore, even though local assemblages are assembled independently on different continents, most regions have converged on similar patterns of proportional richness. Specifically, a few rapidly diversifying clades dominate most communities around the world. The high diversification rates of these clades are then linked to their high dispersal rates. Similar patterns may occur in many groups, such as plants, frogs, salamanders, birds, and mammals.}, } @article {pmid29351015, year = {2018}, author = {Ryan, WH}, title = {Temperature-Dependent Growth and Fission Rate Plasticity Drive Seasonal and Geographic Changes in Body Size in a Clonal Sea Anemone.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {210-219}, doi = {10.1086/695496}, pmid = {29351015}, issn = {1537-5323}, abstract = {The temperature-size rule is a commonly observed pattern where adult body size is negatively correlated with developmental temperature. In part, this may occur as a consequence of allometric scaling, where changes in the ratio of surface area to mass limit oxygen diffusion as body size increases. As oxygen demand increases with temperature, a smaller body should be favored as temperature increases. For clonal animals, small changes in growth and/or fission rate can rapidly alter the average body size of clonal descendants. Here I test the hypothesis that the clonal sea anemone Diadumene lineata is able to track an optimal body size through seasonal temperature changes using fission rate plasticity. Individuals from three regions (Florida, Georgia, and Massachusetts) across the species' latitudinal range were grown in a year-long reciprocal common garden experiment mimicking seasonal temperature changes at three sites. Average body size was found to be smaller and fission rates higher in warmer conditions, consistent with the temperature-size rule pattern. However, seasonal size and fission patterns reflect a complex interaction between region-specific thermal reaction norms and the local temperature regime. These details provide insight into both the range of conditions required for oxygen limitation to contribute to a negative correlation between body size and temperature and the role that fission rate plasticity can play in tracking a rapidly changing optimal phenotype.}, } @article {pmid29351014, year = {2018}, author = {Marchetto, KM and Power, AG}, title = {Coinfection Timing Drives Host Population Dynamics through Changes in Virulence.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {173-183}, doi = {10.1086/695316}, pmid = {29351014}, issn = {1537-5323}, abstract = {Infections of one host by multiple parasites are common, and several studies have found that the order of parasite invasion can affect both within-host competition and disease severity. However, it is unclear to what extent coinfection timing might be important to consider when modeling parasite impacts on host populations. Using a model system of two viruses infecting barley, we found that simultaneous infections of the two viruses were significantly more damaging to hosts than sequential coinfections. While priority effects were evident in within-host concentrations of sequential coinfections, priority did not influence any parameters (such as virulence or transmission rate) that affect host population dynamics. We built a susceptible-infected model to examine whether the observed difference in coinfection virulence could impact host population dynamics under a range of scenarios. We found that coinfection timing can have an important but context-dependent effect on projected host population dynamics. Studies that examine only simultaneous coinfections could inflate disease impact predictions.}, } @article {pmid29351013, year = {2018}, author = {Spriggs, EL and Schmerler, SB and Edwards, EJ and Donoghue, MJ}, title = {Leaf Form Evolution in Viburnum Parallels Variation within Individual Plants.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {235-249}, doi = {10.1086/695337}, pmid = {29351013}, issn = {1537-5323}, abstract = {Few studies have critically evaluated how morphological variation within individual organisms corresponds to variation within and among species. Subindividual variation in plants facilitates such studies because their indeterminate modular growth generates multiple serially homologous structures along growing axes. Focusing on leaf form, we evaluate how subindividual trait variation relates to leaf evolution across Viburnum, a clade of woody angiosperms. In Viburnum we infer multiple independent origins of wide/lobed leaves with toothed margins from ancestors with elliptical, smooth-margined leaves. We document leaf variation along the branches of individual plants of 28 species and among populations across the wide range of Viburnum dentatum. We conclude that when novel leaf forms evolved in Viburnum, they were intercalated at the beginning of the seasonal leaf sequence, which then generated a repeated spectrum of leaf forms along each branch (seasonal heteroblasty). We hypothesize that the existence of such a spectrum then facilitated additional evolutionary shifts, including reversions to more ancestral forms. We argue that the recurrent production of alternative phenotypes provides opportunities to canalize the production of particular forms and that this phenomenon has played an important role in generating macroscale patterns.}, } @article {pmid29351012, year = {2018}, author = {Becker, FS and Tolley, KA and Measey, GJ and Altwegg, R}, title = {Extreme Climate-Induced Life-History Plasticity in an Amphibian.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {250-258}, doi = {10.1086/695315}, pmid = {29351012}, issn = {1537-5323}, abstract = {Age-specific survival and reproduction are closely linked to fitness and therefore subject to strong selection that typically limits their variability within species. Furthermore, adult survival rate in vertebrate populations is typically less variable over time than other life-history traits, such as fecundity or recruitment. Hence, adult survival is often conserved within a population over time, compared to the variation in survival found across taxa. In stark contrast to this general pattern, we report evidence of extreme short-term variation of adult survival in Rose's mountain toadlet (Capensibufo rosei), which is apparently climate induced. Over 7 years, annual survival rate varied between 0.04 and 0.92, and 94% of this variation was explained by variation in breeding-season rainfall. Preliminary results suggest that this variation reflects adaptive life-history plasticity to a degree thus far unrecorded for any vertebrate, rather than direct rainfall-induced mortality. In wet years, these toads appeared to achieve increased reproduction at the expense of their own survival, whereas in dry years, their survival increased at the expense of reproduction. Such environmentally induced plasticity may reflect a diversity of life-history strategies not previously appreciated among vertebrates.}, } @article {pmid29351011, year = {2018}, author = {Battey, CJ and Linck, EB and Epperly, KL and French, C and Slager, DL and Sykes, PW and Klicka, J}, title = {A Migratory Divide in the Painted Bunting (Passerina ciris).}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {259-268}, doi = {10.1086/695439}, pmid = {29351011}, issn = {1537-5323}, abstract = {In the painted bunting (Passerina ciris), a North American songbird, populations on the Atlantic coast and interior southern United States are known to be allopatric during the breeding season, but efforts to map connectivity with wintering ranges have been largely inconclusive. Using genomic and morphological data from museum specimens and banded birds, we found evidence of three genetically differentiated painted bunting populations with distinct wintering ranges and molt-migration phenologies. In addition to confirming that the Atlantic coast population remains allopatric throughout the annual cycle, we identified an unexpected migratory divide within the interior breeding range. Populations breeding in Louisiana winter on the Yucatán Peninsula and are parapatric with other interior populations that winter in mainland Mexico and Central America. Across the interior breeding range, genetic ancestry is also associated with variation in wing length, suggesting that selection may be promoting morphological divergence in populations with different migration strategies.}, } @article {pmid29351010, year = {2018}, author = {Bergeron, ZT and Fuller, RC}, title = {Using Human Vision to Detect Variation in Avian Coloration: How Bad Is It?.}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {269-276}, doi = {10.1086/695282}, pmid = {29351010}, issn = {1537-5323}, abstract = {Assessing variation in animal coloration is difficult, as animals differ in their visual system properties. This has led some to propose that human vision can never be used to evaluate coloration, yet many studies have a long history of relying on human vision. To reconcile these views, we compared the reflectance spectra of preserved avian plumage elements with two measures that are human biased: RGB values from digital photographs and the corresponding reflectance spectra from a field guide. We measured 73 plumage elements across 14 bird species. The field guide reflectance spectra were drastically different from that of the actual birds, particularly for blue elements. However, principal component analyses on all three data sets indicated remarkably similar data structure. We conclude that human vision can detect much of the variation in coloration in the visible range, providing fodder for subsequent studies in ecology, evolution, behavior, and visual ecology.}, } @article {pmid29351009, year = {2018}, author = {Tonnabel, J and Schurr, FM and Boucher, F and Thuiller, W and Renaud, J and Douzery, EJP and Ronce, O}, title = {Life-History Traits Evolved Jointly with Climatic Niche and Disturbance Regime in the Genus Leucadendron (Proteaceae).}, journal = {The American naturalist}, volume = {191}, number = {2}, pages = {220-234}, doi = {10.1086/695283}, pmid = {29351009}, issn = {1537-5323}, abstract = {Organisms have evolved a diversity of life-history strategies to cope with variation in their environment. Persistence as adults and/or seeds across recruitment events allows species to dampen the effects of environmental fluctuations. The evolution of life cycles with overlapping generations should thus permit the colonization of environments with uncertain recruitment. We tested this hypothesis in Leucadendron (Proteaceae), a genus with high functional diversity native to fire-prone habitats in the South African fynbos. We analyzed the joint evolution of life-history traits (adult survival and seed-bank strategies) and ecological niches (climate and fire regime), using comparative methods and accounting for various sources of uncertainty. In the fynbos, species with canopy seed banks that are unable to survive fire as adults display nonoverlapping generations. In contrast, resprouters with an underground seed bank may be less threatened by extreme climatic events and fire intervals, given their iteroparity and long-lasting seed bank. Life cycles with nonoverlapping generations indeed jointly evolved with niches with less exposure to frost but not with those with less exposure to drought. Canopy seed banks jointly evolved with niches with more predictable fire return, compared to underground seed banks. The evolution of extraordinary functional diversity among fynbos plants thus reflects, at least in part, the diversity of both climates and fire regimes in this region.}, } @article {pmid29349925, year = {2018}, author = {Nawrocki, KL and Wetzel, D and Jones, JB and Woods, EC and McBride, SM}, title = {Ethanolamine is a valuable nutrient source that impacts Clostridium difficile pathogenesis.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1419-1435}, pmid = {29349925}, issn = {1462-2920}, support = {T32 GM008169/GM/NIGMS NIH HHS/United States ; T32 AI106699/AI/NIAID NIH HHS/United States ; R03 DK101870/DK/NIDDK NIH HHS/United States ; K01 DK087763/DK/NIDDK NIH HHS/United States ; R56 AI109526/AI/NIAID NIH HHS/United States ; R01 AI116933/AI/NIAID NIH HHS/United States ; }, abstract = {Clostridium (Clostridioides) difficile is a gastrointestinal pathogen that colonizes the intestinal tract of mammals and can cause severe diarrheal disease. Although C. difficile growth is confined to the intestinal tract, our understanding of the specific metabolites and host factors that are important for the growth of the bacterium is limited. In other enteric pathogens, the membrane-derived metabolite, ethanolamine (EA), is utilized as a nutrient source and can function as a signal to initiate the production of virulence factors. In this study, we investigated the effects of ethanolamine and the role of the predicted ethanolamine gene cluster (CD1907-CD1925) on C. difficile growth. Using targeted mutagenesis, we disrupted genes within the eut cluster and assessed their roles in ethanolamine utilization, and the impact of eut disruption on the outcome of infection in a hamster model of disease. Our results indicate that the eut gene cluster is required for the growth of C. difficile on ethanolamine as a primary nutrient source. Further, the inability to utilize ethanolamine resulted in greater virulence and a shorter time to morbidity in the animal model. Overall, these data suggest that ethanolamine is an important nutrient source within the host and that, in contrast to other intestinal pathogens, the metabolism of ethanolamine by C. difficile can delay the onset of disease.}, } @article {pmid29349913, year = {2018}, author = {Gong, W and Paerl, H and Marchetti, A}, title = {Eukaryotic phytoplankton community spatiotemporal dynamics as identified through gene expression within a eutrophic estuary.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1095-1111}, doi = {10.1111/1462-2920.14049}, pmid = {29349913}, issn = {1462-2920}, abstract = {Over the span of a year, we investigated the interactions between biotic and abiotic factors within the eutrophic Neuse River Estuary (NRE). Through metatranscriptomic sequencing in combination with water quality measurements, we show that there are different metabolic strategies deployed along the NRE. In the upper estuary, taxonomically resolved phytoplankton groups express more transcripts of genes for synthesis of cellular components and carbon metabolism whereas in the lower estuary, transcripts allocated to nutrient metabolism and transport were more highly expressed. Metabolisms for polysaccharide synthesis and transportation were elevated in the lower estuary and could be reflective of unbalanced growth and/or interactions with their surrounding microbial consortia. Our results indicate phytoplankton have high metabolic activity, suggestive of increased growth rates in the upper estuary and display patterns reflective of nutrient limitation in the lower estuary. Among all the environmental parameters varying along the NRE, nitrogen availability is found to be the main driving factor for the observed spatial divergence.}, } @article {pmid29349886, year = {2018}, author = {Urdaneta, V and Casadesús, J}, title = {Adaptation of Salmonella enterica to bile: essential role of AcrAB-mediated efflux.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1405-1418}, doi = {10.1111/1462-2920.14047}, pmid = {29349886}, issn = {1462-2920}, abstract = {Adaptation to bile is the ability to endure the lethal effects of bile salts after growth on sublethal concentrations. Surveys of adaptation to bile in Salmonella enterica ser. Tyhimurium reveal that active efflux is essential for adaptation while other bacterial functions involved in bile resistance are not. Among S. enterica mutants lacking one or more efflux systems, only strains lacking AcrAB are unable to adapt, thus revealing an essential role for AcrAB. Transcription of the acrAB operon is upregulated in the presence of a sublethal concentration of sodium deoxycholate (DOC) while other efflux loci are either weakly upregulated or irresponsive. Upregulation of acrAB transcription is strong during exponential growth, and weak in stationary cultures. Single cell analysis of ethidium bromide accumulation indicates that DOC-induced AcrAB-mediated efflux occurs in both exponential and stationary cultures. Upregulation of acrAB expression may thus be crucial at early stages of adaptation, while sustained AcrAB activity may be sufficient to confer bile resistance in nondividing cells.}, } @article {pmid29349600, year = {2018}, author = {Sezmis, AL and Malerba, ME and Marshall, DJ and McDonald, MJ}, title = {Beneficial Mutations from Evolution Experiments Increase Rates of Growth and Fermentation.}, journal = {Journal of molecular evolution}, volume = {86}, number = {2}, pages = {111-117}, doi = {10.1007/s00239-018-9829-9}, pmid = {29349600}, issn = {1432-1432}, support = {FT170100441//Australian Research Council/ ; }, abstract = {A major goal of evolutionary biology is to understand how beneficial mutations translate into increased fitness. Here, we study beneficial mutations that arise in experimental populations of yeast evolved in glucose-rich media. We find that fitness increases are caused by enhanced maximum growth rate (R) that come at the cost of reduced yield (K). We show that for some of these mutants, high R coincides with higher rates of ethanol secretion, suggesting that higher growth rates are due to an increased preference to utilize glucose through the fermentation pathway, instead of respiration. We examine the performance of mutants across gradients of glucose and nitrogen concentrations and show that the preference for fermentation over respiration is influenced by the availability of glucose and nitrogen. Overall, our data show that selection for high growth rates can lead to an enhanced Crabtree phenotype by the way of beneficial mutations that permit aerobic fermentation at a greater range of glucose concentrations.}, } @article {pmid29349599, year = {2018}, author = {Fitzek, E and Joardar, A and Gupta, R and Geisler, M}, title = {Evolution of Eukaryal and Archaeal Pseudouridine Synthase Pus10.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {77-89}, pmid = {29349599}, issn = {1432-1432}, support = {R15 GM055945/GM/NIGMS NIH HHS/United States ; GM55045//National Institutes of Health/ ; }, abstract = {In archaea, pseudouridine (Ψ) synthase Pus10 modifies uridine (U) to Ψ at positions 54 and 55 of tRNA. In contrast, Pus10 is not found in bacteria, where modifications at those two positions are carried out by TrmA (U54 to m5U54) and TruB (U55 to Ψ55). Many eukaryotes have an apparent redundancy; their genomes contain orthologs of archaeal Pus10 and bacterial TrmA and TruB. Although eukaryal Pus10 genes share a conserved catalytic domain with archaeal Pus10 genes, their biological roles are not clear for the two reasons. First, experimental evidence suggests that human Pus10 participates in apoptosis induced by the tumor necrosis factor-related apoptosis-inducing ligand. Whether the function of human Pus10 is in place or in addition to of Ψ synthesis in tRNA is unknown. Second, Pus10 is found in earlier evolutionary branches of fungi (such as chytrid Batrachochytrium) but is absent in all dikaryon fungi surveyed (Ascomycetes and Basidiomycetes). We did a comprehensive analysis of sequenced genomes and found that orthologs of Pus10, TrmA, and TruB were present in all the animals, plants, and protozoa surveyed. This indicates that the common eukaryotic ancestor possesses all the three genes. Next, we examined 116 archaeal and eukaryotic Pus10 protein sequences to find that Pus10 existed as a single copy gene in all the surveyed genomes despite ancestral whole genome duplications had occurred. This indicates a possible deleterious gene dosage effect. Our results suggest that functional redundancy result in gene loss or neofunctionalization in different evolutionary lineages.}, } @article {pmid29348708, year = {2018}, author = {Fér, T and Schmickl, RE}, title = {HybPhyloMaker: Target Enrichment Data Analysis From Raw Reads to Species Trees.}, journal = {Evolutionary bioinformatics online}, volume = {14}, number = {}, pages = {1176934317742613}, pmid = {29348708}, issn = {1176-9343}, abstract = {Summary: Hybridization-based target enrichment in combination with genome skimming (Hyb-Seq) is becoming a standard method of phylogenomics. We developed HybPhyloMaker, a bioinformatics pipeline that performs target enrichment data analysis from raw reads to supermatrix-, supertree-, and multispecies coalescent-based species tree reconstruction. HybPhyloMaker is written in BASH and integrates common bioinformatics tools. It can be launched both locally and on a high-performance computer cluster. Compared with existing target enrichment data analysis pipelines, HybPhyloMaker offers the following main advantages: implementation of all steps of data analysis from raw reads to species tree reconstruction, calculation and summary of alignment and gene tree properties that assist the user in the selection of "quality-filtered" genes, implementation of several species tree reconstruction methods, and analysis of the coding regions of organellar genomes.

Availability: The HybPhyloMaker scripts, manual as well as a test data set, are available in https://github.com/tomas-fer/HybPhyloMaker/. HybPhyloMaker is licensed under open-source license GPL v.3 allowing further modifications.}, } @article {pmid29348647, year = {2018}, author = {O'Bryan, CJ and Braczkowski, AR and Beyer, HL and Carter, NH and Watson, JEM and McDonald-Madden, E}, title = {The contribution of predators and scavengers to human well-being.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {229-236}, doi = {10.1038/s41559-017-0421-2}, pmid = {29348647}, issn = {2397-334X}, abstract = {Predators and scavengers are frequently persecuted for their negative effects on property, livestock and human life. Research has shown that these species play important regulatory roles in intact ecosystems including regulating herbivore and mesopredator populations that in turn affect floral, soil and hydrological systems. Yet predators and scavengers receive surprisingly little recognition for their benefits to humans in the landscapes they share. We review these benefits, highlighting the most recent studies that have documented their positive effects across a range of environments. Indeed, the benefits of predators and scavengers can be far reaching, affecting human health and well-being through disease mitigation, agricultural production and waste-disposal services. As many predators and scavengers are in a state of rapid decline, we argue that researchers must work in concert with the media, managers and policymakers to highlight benefits of these species and the need to ensure their long-term conservation. Furthermore, instead of assessing the costs of predators and scavengers only in economic terms, it is critical to recognize their beneficial contributions to human health and well-being. Given the ever-expanding human footprint, it is essential that we construct conservation solutions that allow a wide variety of species to persist in shared landscapes. Identifying, evaluating and communicating the benefits provided by species that are often considered problem animals is an important step for establishing tolerance in these shared spaces.}, } @article {pmid29348646, year = {2018}, author = {Treves, A and Artelle, KA and Darimont, CT and Lynn, WS and Paquet, P and Santiago-Ávila, FJ and Shaw, R and Wood, MC}, title = {Intergenerational equity can help to prevent climate change and extinction.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {204-207}, doi = {10.1038/s41559-018-0465-y}, pmid = {29348646}, issn = {2397-334X}, } @article {pmid29348645, year = {2018}, author = {Bird, CS and Veríssimo, A and Magozzi, S and Abrantes, KG and Aguilar, A and Al-Reasi, H and Barnett, A and Bethea, DM and Biais, G and Borrell, A and Bouchoucha, M and Boyle, M and Brooks, EJ and Brunnschweiler, J and Bustamante, P and Carlisle, A and Catarino, D and Caut, S and Cherel, Y and Chouvelon, T and Churchill, D and Ciancio, J and Claes, J and Colaço, A and Courtney, DL and Cresson, P and Daly, R and de Necker, L and Endo, T and Figueiredo, I and Frisch, AJ and Hansen, JH and Heithaus, M and Hussey, NE and Iitembu, J and Juanes, F and Kinney, MJ and Kiszka, JJ and Klarian, SA and Kopp, D and Leaf, R and Li, Y and Lorrain, A and Madigan, DJ and Maljković, A and Malpica-Cruz, L and Matich, P and Meekan, MG and Ménard, F and Menezes, GM and Munroe, SEM and Newman, MC and Papastamatiou, YP and Pethybridge, H and Plumlee, JD and Polo-Silva, C and Quaeck-Davies, K and Raoult, V and Reum, J and Torres-Rojas, YE and Shiffman, DS and Shipley, ON and Speed, CW and Staudinger, MD and Teffer, AK and Tilley, A and Valls, M and Vaudo, JJ and Wai, TC and Wells, RJD and Wyatt, ASJ and Yool, A and Trueman, CN}, title = {A global perspective on the trophic geography of sharks.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {299-305}, doi = {10.1038/s41559-017-0432-z}, pmid = {29348645}, issn = {2397-334X}, abstract = {Sharks are a diverse group of mobile predators that forage across varied spatial scales and have the potential to influence food web dynamics. The ecological consequences of recent declines in shark biomass may extend across broader geographic ranges if shark taxa display common behavioural traits. By tracking the original site of photosynthetic fixation of carbon atoms that were ultimately assimilated into muscle tissues of 5,394 sharks from 114 species, we identify globally consistent biogeographic traits in trophic interactions between sharks found in different habitats. We show that populations of shelf-dwelling sharks derive a substantial proportion of their carbon from regional pelagic sources, but contain individuals that forage within additional isotopically diverse local food webs, such as those supported by terrestrial plant sources, benthic production and macrophytes. In contrast, oceanic sharks seem to use carbon derived from between 30° and 50° of latitude. Global-scale compilations of stable isotope data combined with biogeochemical modelling generate hypotheses regarding animal behaviours that can be tested with other methodological approaches.}, } @article {pmid29348644, year = {2018}, author = {Stein, RW and Mull, CG and Kuhn, TS and Aschliman, NC and Davidson, LNK and Joy, JB and Smith, GJ and Dulvy, NK and Mooers, AO}, title = {Global priorities for conserving the evolutionary history of sharks, rays and chimaeras.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {288-298}, doi = {10.1038/s41559-017-0448-4}, pmid = {29348644}, issn = {2397-334X}, abstract = {In an era of accelerated biodiversity loss and limited conservation resources, systematic prioritization of species and places is essential. In terrestrial vertebrates, evolutionary distinctness has been used to identify species and locations that embody the greatest share of evolutionary history. We estimate evolutionary distinctness for a large marine vertebrate radiation on a dated taxon-complete tree for all 1,192 chondrichthyan fishes (sharks, rays and chimaeras) by augmenting a new 610-species molecular phylogeny using taxonomic constraints. Chondrichthyans are by far the most evolutionarily distinct of all major radiations of jawed vertebrates-the average species embodies 26 million years of unique evolutionary history. With this metric, we identify 21 countries with the highest richness, endemism and evolutionary distinctness of threatened species as targets for conservation prioritization. On average, threatened chondrichthyans are more evolutionarily distinct-further motivating improved conservation, fisheries management and trade regulation to avoid significant pruning of the chondrichthyan tree of life.}, } @article {pmid29348643, year = {2018}, author = {Goymer, P}, title = {A trillion trees.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {208-209}, doi = {10.1038/s41559-018-0464-z}, pmid = {29348643}, issn = {2397-334X}, } @article {pmid29348642, year = {2018}, author = {Rabett, RJ}, title = {The success of failed Homo sapiens dispersals out of Africa and into Asia.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {212-219}, doi = {10.1038/s41559-017-0436-8}, pmid = {29348642}, issn = {2397-334X}, abstract = {The evidence for an early dispersal of Homo sapiens from Africa into the Levant during Marine Isotope Stage 5 (MIS-5) 126-74 ka (thousand years ago) was characterized for many years as an 'abortive' expansion: a precursor to a sustained dispersal from which all extant human populations can be traced. Recent archaeological and genetic data from both western and eastern parts of Eurasia and from Australia are starting to challenge that interpretation. This Perspective reviews the current evidence for a scenario where the MIS-5 dispersal encompassed a much greater geographic distribution and temporal duration. The implications of this for tracking and understanding early human dispersal in Southeast Asia specifically are considered, and the validity of measuring dispersal success only through genetic continuity into the present is examined.}, } @article {pmid29348641, year = {2018}, author = {Hammarlund, EU and von Stedingk, K and Påhlman, S}, title = {Refined control of cell stemness allowed animal evolution in the oxic realm.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {220-228}, doi = {10.1038/s41559-017-0410-5}, pmid = {29348641}, issn = {2397-334X}, abstract = {Animal diversification on Earth has long been presumed to be associated with the increasing extent of oxic niches. Here, we challenge that view. We start with the fact that hypoxia (<1-3% O2) maintains cellular immaturity (stemness), whereas adult stem cells continuously-and paradoxically-regenerate animal tissue in oxygenated settings. Novel insights from tumour biology illuminate how cell stemness nevertheless can be achieved through the action of oxygen-sensing transcription factors in oxygenated, regenerating tissue. We suggest that these hypoxia-inducible transcription factors provided animals with unprecedented control over cell stemness that allowed them to cope with fluctuating oxygen concentrations. Thus, a refinement of the cellular hypoxia-response machinery enabled cell stemness at oxic conditions and, then, animals to evolve into the oxic realm. This view on the onset of animal diversification is consistent with geological evidence and provides a new perspective on the challenges and evolution of multicellular life.}, } @article {pmid29348640, year = {2018}, author = {}, title = {Predators on top.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {199}, doi = {10.1038/s41559-018-0472-z}, pmid = {29348640}, issn = {2397-334X}, } @article {pmid29348368, year = {2018}, author = {Costa, EA and Subramanian, K and Nunnari, J and Weissman, JS}, title = {Defining the physiological role of SRP in protein-targeting efficiency and specificity.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {689-692}, pmid = {29348368}, issn = {1095-9203}, support = {/HHMI/Howard Hughes Medical Institute/United States ; P50 GM102706/GM/NIGMS NIH HHS/United States ; R01 GM097432/GM/NIGMS NIH HHS/United States ; R01 AG041826/AG/NIA NIH HHS/United States ; R01 GM062942/GM/NIGMS NIH HHS/United States ; R01 GM106019/GM/NIGMS NIH HHS/United States ; }, mesh = {Endoplasmic Reticulum/metabolism ; Indoleacetic Acids/pharmacology ; Mitochondria/metabolism ; *Protein Sorting Signals ; Protein Transport ; Proteolysis/drug effects ; RNA, Messenger/metabolism ; Ribosomes/metabolism ; Saccharomyces cerevisiae/drug effects/*metabolism ; Signal Recognition Particle/*metabolism ; }, abstract = {The signal recognition particle (SRP) enables cotranslational delivery of proteins for translocation into the endoplasmic reticulum (ER), but its full in vivo role remains incompletely explored. We combined rapid auxin-induced SRP degradation with proximity-specific ribosome profiling to define SRP's in vivo function in yeast. Despite the classic view that SRP recognizes amino-terminal signal sequences, we show that SRP was generally essential for targeting transmembrane domains regardless of their position relative to the amino terminus. By contrast, many proteins containing cleavable amino-terminal signal peptides were efficiently cotranslationally targeted in SRP's absence. We also reveal an unanticipated consequence of SRP loss: Transcripts normally targeted to the ER were mistargeted to mitochondria, leading to mitochondrial defects. These results elucidate SRP's essential roles in maintaining the efficiency and specificity of protein targeting.}, } @article {pmid29348367, year = {2018}, author = {Gibcus, JH and Samejima, K and Goloborodko, A and Samejima, I and Naumova, N and Nuebler, J and Kanemaki, MT and Xie, L and Paulson, JR and Earnshaw, WC and Mirny, LA and Dekker, J}, title = {A pathway for mitotic chromosome formation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {}, pmid = {29348367}, issn = {1095-9203}, support = {R01 GM114190/GM/NIGMS NIH HHS/United States ; R01 HG003143/HG/NHGRI NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; U54 DK107980/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; U54 CA193419/CA/NCI NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/metabolism ; Animals ; Cell Line ; Chromosomes/*chemistry/*genetics ; Computational Biology ; DNA-Binding Proteins/metabolism ; Genomics ; Interphase ; *Mitosis ; Multiprotein Complexes/metabolism ; Prometaphase ; Prophase ; Xenopus laevis ; }, abstract = {Mitotic chromosomes fold as compact arrays of chromatin loops. To identify the pathway of mitotic chromosome formation, we combined imaging and Hi-C analysis of synchronous DT40 cell cultures with polymer simulations. Here we show that in prophase, the interphase organization is rapidly lost in a condensin-dependent manner, and arrays of consecutive 60-kilobase (kb) loops are formed. During prometaphase, ~80-kb inner loops are nested within ~400-kb outer loops. The loop array acquires a helical arrangement with consecutive loops emanating from a central "spiral staircase" condensin scaffold. The size of helical turns progressively increases to ~12 megabases during prometaphase. Acute depletion of condensin I or II shows that nested loops form by differential action of the two condensins, whereas condensin II is required for helical winding.}, } @article {pmid29348366, year = {2018}, author = {Kasinath, V and Faini, M and Poepsel, S and Reif, D and Feng, XA and Stjepanovic, G and Aebersold, R and Nogales, E}, title = {Structures of human PRC2 with its cofactors AEBP2 and JARID2.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {940-944}, pmid = {29348366}, issn = {1095-9203}, support = {233226//European Research Council/International ; /HHMI/Howard Hughes Medical Institute/United States ; //Howard Hughes Medical Institute/United States ; 670821//European Research Council/International ; //European Research Council/International ; }, mesh = {Cryoelectron Microscopy ; Histones/chemistry ; Humans ; Methylation ; Polycomb Repressive Complex 2/*chemistry/ultrastructure ; Protein Binding ; Protein Conformation ; Repressor Proteins/*chemistry/ultrastructure ; }, abstract = {Transcriptionally repressive histone H3 lysine 27 methylation by Polycomb repressive complex 2 (PRC2) is essential for cellular differentiation and development. Here we report cryo-electron microscopy structures of human PRC2 in a basal state and two distinct active states while in complex with its cofactors JARID2 and AEBP2. Both cofactors mimic the binding of histone H3 tails. JARID2, methylated by PRC2, mimics a methylated H3 tail to stimulate PRC2 activity, whereas AEBP2 interacts with the RBAP48 subunit, mimicking an unmodified H3 tail. SUZ12 interacts with all other subunits within the assembly and thus contributes to the stability of the complex. Our analysis defines the complete architecture of a functionally relevant PRC2 and provides a structural framework to understand its regulation by cofactors, histone tails, and RNA.}, } @article {pmid29348365, year = {2018}, author = {Cohen, JD and Li, L and Wang, Y and Thoburn, C and Afsari, B and Danilova, L and Douville, C and Javed, AA and Wong, F and Mattox, A and Hruban, RH and Wolfgang, CL and Goggins, MG and Dal Molin, M and Wang, TL and Roden, R and Klein, AP and Ptak, J and Dobbyn, L and Schaefer, J and Silliman, N and Popoli, M and Vogelstein, JT and Browne, JD and Schoen, RE and Brand, RE and Tie, J and Gibbs, P and Wong, HL and Mansfield, AS and Jen, J and Hanash, SM and Falconi, M and Allen, PJ and Zhou, S and Bettegowda, C and Diaz, LA and Tomasetti, C and Kinzler, KW and Vogelstein, B and Lennon, AM and Papadopoulos, N}, title = {Detection and localization of surgically resectable cancers with a multi-analyte blood test.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6378}, pages = {926-930}, pmid = {29348365}, issn = {1095-9203}, support = {U01 CA200469/CA/NCI NIH HHS/United States ; T32 GM007309/GM/NIGMS NIH HHS/United States ; P50 CA062924/CA/NCI NIH HHS/United States ; P30 CA006973/CA/NCI NIH HHS/United States ; U01 CA152753/CA/NCI NIH HHS/United States ; F32 CA069731/CA/NCI NIH HHS/United States ; P50 CA102701/CA/NCI NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; R01 GM073095/GM/NIGMS NIH HHS/United States ; T32 GM008752/GM/NIGMS NIH HHS/United States ; }, mesh = {Circulating Tumor DNA/*genetics ; Costs and Cost Analysis ; Early Detection of Cancer/economics/*methods ; *Hematologic Tests/economics ; Humans ; Mutation ; Neoplasm Proteins/*blood ; Neoplasms/blood/*diagnosis/genetics/*surgery ; Polymerase Chain Reaction/methods ; }, abstract = {Earlier detection is key to reducing cancer deaths. Here, we describe a blood test that can detect eight common cancer types through assessment of the levels of circulating proteins and mutations in cell-free DNA. We applied this test, called CancerSEEK, to 1005 patients with nonmetastatic, clinically detected cancers of the ovary, liver, stomach, pancreas, esophagus, colorectum, lung, or breast. CancerSEEK tests were positive in a median of 70% of the eight cancer types. The sensitivities ranged from 69 to 98% for the detection of five cancer types (ovary, liver, stomach, pancreas, and esophagus) for which there are no screening tests available for average-risk individuals. The specificity of CancerSEEK was greater than 99%: only 7 of 812 healthy controls scored positive. In addition, CancerSEEK localized the cancer to a small number of anatomic sites in a median of 83% of the patients.}, } @article {pmid29348364, year = {2018}, author = {Lin, QY and Mason, JA and Li, Z and Zhou, W and O'Brien, MN and Brown, KA and Jones, MR and Butun, S and Lee, B and Dravid, VP and Aydin, K and Mirkin, CA}, title = {Building superlattices from individual nanoparticles via template-confined DNA-mediated assembly.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {669-672}, doi = {10.1126/science.aaq0591}, pmid = {29348364}, issn = {1095-9203}, abstract = {DNA programmable assembly has been combined with top-down lithography to construct superlattices of discrete, reconfigurable nanoparticle architectures on a gold surface over large areas. Specifically, the assembly of individual colloidal plasmonic nanoparticles with different shapes and sizes is controlled by oligonucleotides containing "locked" nucleic acids and confined environments provided by polymer pores to yield oriented architectures that feature tunable arrangements and independently controllable distances at both nanometer- and micrometer-length scales. These structures, which would be difficult to construct by other common assembly methods, provide a platform to systematically study and control light-matter interactions in nanoparticle-based optical materials. The generality and potential of this approach are explored by identifying a broadband absorber with a solvent polarity response that allows dynamic tuning of visible light absorption.}, } @article {pmid29348363, year = {2018}, author = {Zhang, D and Zhu, Y and Liu, L and Ying, X and Hsiung, CE and Sougrat, R and Li, K and Han, Y}, title = {Atomic-resolution transmission electron microscopy of electron beam-sensitive crystalline materials.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {675-679}, doi = {10.1126/science.aao0865}, pmid = {29348363}, issn = {1095-9203}, abstract = {High-resolution imaging of electron beam-sensitive materials is one of the most difficult applications of transmission electron microscopy (TEM). The challenges are manifold, including the acquisition of images with extremely low beam doses, the time-constrained search for crystal zone axes, the precise image alignment, and the accurate determination of the defocus value. We develop a suite of methods to fulfill these requirements and acquire atomic-resolution TEM images of several metal organic frameworks that are generally recognized as highly sensitive to electron beams. The high image resolution allows us to identify individual metal atomic columns, various types of surface termination, and benzene rings in the organic linkers. We also apply our methods to other electron beam-sensitive materials, including the organic-inorganic hybrid perovskite CH3NH3PbBr3.}, } @article {pmid29348239, year = {2018}, author = {Tregoning, J}, title = {From parade ground to PI.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {362}, doi = {10.1126/science.359.6373.362}, pmid = {29348239}, issn = {1095-9203}, } @article {pmid29348238, year = {2018}, author = {Thongsomboon, W and Serra, DO and Possling, A and Hadjineophytou, C and Hengge, R and Cegelski, L}, title = {Phosphoethanolamine cellulose: A naturally produced chemically modified cellulose.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {334-338}, doi = {10.1126/science.aao4096}, pmid = {29348238}, issn = {1095-9203}, mesh = {Biofilms ; Cellulose/*biosynthesis/*chemistry/genetics ; Escherichia coli/*enzymology/genetics ; Escherichia coli Proteins/genetics/*metabolism ; Ethanolamines/chemistry/*metabolism ; Operon/genetics/*physiology ; }, abstract = {Cellulose is a major contributor to the chemical and mechanical properties of plants and assumes structural roles in bacterial communities termed biofilms. We find that Escherichia coli produces chemically modified cellulose that is required for extracellular matrix assembly and biofilm architecture. Solid-state nuclear magnetic resonance spectroscopy of the intact and insoluble material elucidates the zwitterionic phosphoethanolamine modification that had evaded detection by conventional methods. Installation of the phosphoethanolamine group requires BcsG, a proposed phosphoethanolamine transferase, with biofilm-promoting cyclic diguanylate monophosphate input through a BcsE-BcsF-BcsG transmembrane signaling pathway. The bcsEFG operon is present in many bacteria, including Salmonella species, that also produce the modified cellulose. The discovery of phosphoethanolamine cellulose and the genetic and molecular basis for its production offers opportunities to modulate its production in bacteria and inspires efforts to biosynthetically engineer alternatively modified cellulosic materials.}, } @article {pmid29348237, year = {2018}, author = {Bansak, K and Ferwerda, J and Hainmueller, J and Dillon, A and Hangartner, D and Lawrence, D and Weinstein, J}, title = {Improving refugee integration through data-driven algorithmic assignment.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {325-329}, doi = {10.1126/science.aao4408}, pmid = {29348237}, issn = {1095-9203}, mesh = {Algorithms ; *Community Integration ; *Emigration and Immigration ; Employment ; Humans ; *Refugees ; Switzerland ; United States ; }, abstract = {Developed democracies are settling an increased number of refugees, many of whom face challenges integrating into host societies. We developed a flexible data-driven algorithm that assigns refugees across resettlement locations to improve integration outcomes. The algorithm uses a combination of supervised machine learning and optimal matching to discover and leverage synergies between refugee characteristics and resettlement sites. The algorithm was tested on historical registry data from two countries with different assignment regimes and refugee populations, the United States and Switzerland. Our approach led to gains of roughly 40 to 70%, on average, in refugees' employment outcomes relative to current assignment practices. This approach can provide governments with a practical and cost-efficient policy tool that can be immediately implemented within existing institutional structures.}, } @article {pmid29348236, year = {2018}, author = {Delgado-Baquerizo, M and Oliverio, AM and Brewer, TE and Benavent-González, A and Eldridge, DJ and Bardgett, RD and Maestre, FT and Singh, BK and Fierer, N}, title = {A global atlas of the dominant bacteria found in soil.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {320-325}, doi = {10.1126/science.aap9516}, pmid = {29348236}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Atlases as Topic ; Bacteria/*classification/isolation & purification ; *Microbial Consortia ; Phylogeny ; *Soil Microbiology ; }, abstract = {The immense diversity of soil bacterial communities has stymied efforts to characterize individual taxa and document their global distributions. We analyzed soils from 237 locations across six continents and found that only 2% of bacterial phylotypes (~500 phylotypes) consistently accounted for almost half of the soil bacterial communities worldwide. Despite the overwhelming diversity of bacterial communities, relatively few bacterial taxa are abundant in soils globally. We clustered these dominant taxa into ecological groups to build the first global atlas of soil bacterial taxa. Our study narrows down the immense number of bacterial taxa to a "most wanted" list that will be fruitful targets for genomic and cultivation-based efforts aimed at improving our understanding of soil microbes and their contributions to ecosystem functioning.}, } @article {pmid29348235, year = {2018}, author = {Kitson, PJ and Marie, G and Francoia, JP and Zalesskiy, SS and Sigerson, RC and Mathieson, JS and Cronin, L}, title = {Digitization of multistep organic synthesis in reactionware for on-demand pharmaceuticals.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {314-319}, doi = {10.1126/science.aao3466}, pmid = {29348235}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Baclofen/chemical synthesis ; Chemistry Techniques, Synthetic/*instrumentation/*methods ; GABA-B Receptor Agonists/chemical synthesis ; Pharmaceutical Preparations/*chemical synthesis ; Plastics ; *Printing, Three-Dimensional ; }, abstract = {Chemical manufacturing is often done at large facilities that require a sizable capital investment and then produce key compounds for a finite period. We present an approach to the manufacturing of fine chemicals and pharmaceuticals in a self-contained plastic reactionware device. The device was designed and constructed by using a chemical to computer-automated design (ChemCAD) approach that enables the translation of traditional bench-scale synthesis into a platform-independent digital code. This in turn guides production of a three-dimensional printed device that encloses the entire synthetic route internally via simple operations. We demonstrate the approach for the γ-aminobutyric acid receptor agonist, (±)-baclofen, establishing a concept that paves the way for the local manufacture of drugs outside of specialist facilities.}, } @article {pmid29348234, year = {2018}, author = {Yeom, J and Santos, US and Chekini, M and Cha, M and de Moura, AF and Kotov, NA}, title = {Chiromagnetic nanoparticles and gels.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {309-314}, doi = {10.1126/science.aao7172}, pmid = {29348234}, issn = {1095-9203}, abstract = {Chiral inorganic nanostructures have high circular dichroism, but real-time control of their optical activity has so far been achieved only by irreversible chemical changes. Field modulation is a far more desirable path to chiroptical devices. We hypothesized that magnetic field modulation can be attained for chiral nanostructures with large contributions of the magnetic transition dipole moments to polarization rotation. We found that dispersions and gels of paramagnetic Co3O4 nanoparticles with chiral distortions of the crystal lattices exhibited chiroptical activity in the visible range that was 10 times as strong as that of nonparamagnetic nanoparticles of comparable size. Transparency of the nanoparticle gels to circularly polarized light beams in the ultraviolet range was reversibly modulated by magnetic fields. These phenomena were also observed for other nanoscale metal oxides with lattice distortions from imprinted amino acids and other chiral ligands. The large family of chiral ceramic nanostructures and gels can be pivotal for new technologies and knowledge at the nexus of chirality and magnetism.}, } @article {pmid29348233, year = {2018}, author = {Schultz, R and Atkinson, G and Eaton, DW and Gu, YJ and Kao, H}, title = {Hydraulic fracturing volume is associated with induced earthquake productivity in the Duvernay play.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {304-308}, doi = {10.1126/science.aao0159}, pmid = {29348233}, issn = {1095-9203}, abstract = {A sharp increase in the frequency of earthquakes near Fox Creek, Alberta, began in December 2013 in response to hydraulic fracturing. Using a hydraulic fracturing database, we explore relationships between injection parameters and seismicity response. We show that induced earthquakes are associated with completions that used larger injection volumes (104 to 105 cubic meters) and that seismic productivity scales linearly with injection volume. Injection pressure and rate have an insignificant association with seismic response. Further findings suggest that geological factors play a prominent role in seismic productivity, as evidenced by spatial correlations. Together, volume and geological factors account for ~96% of the variability in the induced earthquake rate near Fox Creek. This result is quantified by a seismogenic index-modified frequency-magnitude distribution, providing a framework to forecast induced seismicity.}, } @article {pmid29348232, year = {2018}, author = {Kopperger, E and List, J and Madhira, S and Rothfischer, F and Lamb, DC and Simmel, FC}, title = {A self-assembled nanoscale robotic arm controlled by electric fields.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {296-301}, doi = {10.1126/science.aao4284}, pmid = {29348232}, issn = {1095-9203}, abstract = {The use of dynamic, self-assembled DNA nanostructures in the context of nanorobotics requires fast and reliable actuation mechanisms. We therefore created a 55-nanometer-by-55-nanometer DNA-based molecular platform with an integrated robotic arm of length 25 nanometers, which can be extended to more than 400 nanometers and actuated with externally applied electrical fields. Precise, computer-controlled switching of the arm between arbitrary positions on the platform can be achieved within milliseconds, as demonstrated with single-pair Förster resonance energy transfer experiments and fluorescence microscopy. The arm can be used for electrically driven transport of molecules or nanoparticles over tens of nanometers, which is useful for the control of photonic and plasmonic processes. Application of piconewton forces by the robot arm is demonstrated in force-induced DNA duplex melting experiments.}, } @article {pmid29348231, year = {2018}, author = {Du, Y and Xin, L and Shi, Y and Zhang, TH and Wu, NC and Dai, L and Gong, D and Brar, G and Shu, S and Luo, J and Reiley, W and Tseng, YW and Bai, H and Wu, TT and Wang, J and Shu, Y and Sun, R}, title = {Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {290-296}, doi = {10.1126/science.aan8806}, pmid = {29348231}, issn = {1095-9203}, support = {R01 HL113655/HL/NHLBI NIH HHS/United States ; P01 CA177322/CA/NCI NIH HHS/United States ; R01 DE023591/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Ferrets ; Genetic Fitness ; Genome, Viral ; Genome-Wide Association Study ; Humans ; Immunity, Cellular ; Immunogenicity, Vaccine/*genetics ; Influenza A virus/drug effects/*genetics/*immunology ; Influenza Vaccines/*genetics/*immunology ; Influenza, Human/*prevention & control ; Interferons/*immunology/pharmacology ; Mice ; Mutation ; Orthomyxoviridae Infections/prevention & control ; Virus Replication/genetics ; }, abstract = {In conventional attenuated viral vaccines, immunogenicity is often suboptimal. Here we present a systematic approach for vaccine development that eliminates interferon (IFN)-modulating functions genome-wide while maintaining virus replication fitness. We applied a quantitative high-throughput genomics system to influenza A virus that simultaneously measured the replication fitness and IFN sensitivity of mutations across the entire genome. By incorporating eight IFN-sensitive mutations, we generated a hyper-interferon-sensitive (HIS) virus as a vaccine candidate. HIS virus is highly attenuated in IFN-competent hosts but able to induce transient IFN responses, elicits robust humoral and cellular immune responses, and provides protection against homologous and heterologous viral challenges. Our approach, which attenuates the virus and promotes immune responses concurrently, is broadly applicable for vaccine development against other pathogens.}, } @article {pmid29348230, year = {2018}, author = {Specker Sullivan, LE}, title = {Have your momos and eat them, too.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {284}, doi = {10.1126/science.aar8472}, pmid = {29348230}, issn = {1095-9203}, mesh = {*Buddhism ; Diet, Vegetarian/*ethics ; Eating ; India ; *Meat ; Monks/*ethics ; Vegetarians ; }, } @article {pmid29348229, year = {2018}, author = {Plotkin, SA and Offit, P and Bégué, P}, title = {Vaccine mandates in France will save lives.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {283-284}, doi = {10.1126/science.aar4422}, pmid = {29348229}, issn = {1095-9203}, mesh = {France ; Humans ; *Vaccines ; }, } @article {pmid29348228, year = {2018}, author = {Antonelli, A and Perrigo, A}, title = {The pitfalls of taking science to the public.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {283}, doi = {10.1126/science.aar8468}, pmid = {29348228}, issn = {1095-9203}, } @article {pmid29348227, year = {2018}, author = {Raff, M}, title = {Ben Barres (1954-2017).}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {280}, doi = {10.1126/science.aas9270}, pmid = {29348227}, issn = {1095-9203}, mesh = {*Brain ; History, 20th Century ; History, 21st Century ; *Neuroglia ; Neurosciences/*history ; United States ; }, } @article {pmid29348226, year = {2018}, author = {Högberg, B}, title = {Remote control of nanoscale devices.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {279}, doi = {10.1126/science.aar6580}, pmid = {29348226}, issn = {1095-9203}, } @article {pmid29348225, year = {2018}, author = {Teijaro, JR and Burton, DR}, title = {Taking down defenses to improve vaccines.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {277-278}, doi = {10.1126/science.aar5421}, pmid = {29348225}, issn = {1095-9203}, mesh = {Humans ; *Vaccines ; }, } @article {pmid29348224, year = {2018}, author = {Galperin, MY and Shalaeva, DN}, title = {A bacterial coat that is not pure cotton.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {276-277}, doi = {10.1126/science.aar5253}, pmid = {29348224}, issn = {1095-9203}, mesh = {*Bacteria ; Bacterial Proteins ; Cellulose ; Humans ; }, } @article {pmid29348223, year = {2018}, author = {Ferrier-Barbut, I and Pfau, T}, title = {Quantum liquids get thin.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {274-275}, doi = {10.1126/science.aar3785}, pmid = {29348223}, issn = {1095-9203}, mesh = {*Deglutition ; *Quantum Theory ; }, } @article {pmid29348222, year = {2018}, author = {Hornung, CH}, title = {The art of manufacturing molecules.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {273-274}, doi = {10.1126/science.aar4543}, pmid = {29348222}, issn = {1095-9203}, mesh = {Chemical Engineering ; *Computer-Aided Design ; Drug Utilization ; Humans ; *Printing, Three-Dimensional ; }, } @article {pmid29348221, year = {2018}, author = {Díaz, S and Pascual, U and Stenseke, M and Martín-López, B and Watson, RT and Molnár, Z and Hill, R and Chan, KMA and Baste, IA and Brauman, KA and Polasky, S and Church, A and Lonsdale, M and Larigauderie, A and Leadley, PW and van Oudenhoven, APE and van der Plaat, F and Schröter, M and Lavorel, S and Aumeeruddy-Thomas, Y and Bukvareva, E and Davies, K and Demissew, S and Erpul, G and Failler, P and Guerra, CA and Hewitt, CL and Keune, H and Lindley, S and Shirayama, Y}, title = {Assessing nature's contributions to people.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {270-272}, doi = {10.1126/science.aap8826}, pmid = {29348221}, issn = {1095-9203}, mesh = {*Biodiversity ; Humans ; Natural Science Disciplines/*trends ; Public Policy ; }, } @article {pmid29348220, year = {2018}, author = {Wade, L}, title = {The believer.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {264-268}, doi = {10.1126/science.359.6373.264}, pmid = {29348220}, issn = {1095-9203}, } @article {pmid29348219, year = {2018}, author = {Matacic, C}, title = {Are algorithms good judges?.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {263}, doi = {10.1126/science.359.6373.263}, pmid = {29348219}, issn = {1095-9203}, mesh = {*Algorithms ; *Criminal Law ; Humans ; Risk Assessment ; }, } @article {pmid29348218, year = {2018}, author = {Wadman, M}, title = {Rochester roiled by fallout from sexual harassment case.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {262-263}, doi = {10.1126/science.359.6373.262}, pmid = {29348218}, issn = {1095-9203}, } @article {pmid29348217, year = {2018}, author = {Stokstad, E}, title = {Tensions flare over electric fishing in European waters.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {261}, doi = {10.1126/science.359.6373.261}, pmid = {29348217}, issn = {1095-9203}, mesh = {Animals ; *Aquatic Organisms ; Conservation of Natural Resources/*legislation & jurisprudence/*methods ; Electricity ; Fisheries/*legislation & jurisprudence ; Netherlands ; }, } @article {pmid29348216, year = {2018}, author = {Pennisi, E}, title = {Tamed immune reaction aids pregnancy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {260}, doi = {10.1126/science.359.6373.260}, pmid = {29348216}, issn = {1095-9203}, mesh = {Abortion, Spontaneous/immunology ; Animals ; Biological Evolution ; Decidua/immunology ; Embryo Implantation/*immunology ; Female ; Humans ; Infertility/immunology/therapy ; Inflammation/*immunology ; Opossums ; Parturition/*immunology ; Pregnancy ; }, } @article {pmid29348215, year = {2018}, author = {Kaiser, J}, title = {'Liquid biopsy' for cancer promises early detection.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {259}, doi = {10.1126/science.359.6373.259}, pmid = {29348215}, issn = {1095-9203}, mesh = {Biomarkers, Tumor/*blood ; Early Detection of Cancer/*methods ; Hematologic Tests ; Humans ; *Liquid Biopsy ; Neoplasms/*blood/*diagnosis ; }, } @article {pmid29348214, year = {2018}, author = {Clery, D}, title = {Newborn exoplanet eyed for moons and rings.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {258}, doi = {10.1126/science.359.6373.258}, pmid = {29348214}, issn = {1095-9203}, } @article {pmid29348213, year = {2018}, author = {}, title = {News at a glance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {256-257}, doi = {10.1126/science.359.6373.256}, pmid = {29348213}, issn = {1095-9203}, } @article {pmid29348212, year = {2018}, author = {Belser, JA and Tumpey, TM}, title = {The 1918 flu, 100 years later.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {255}, doi = {10.1126/science.aas9565}, pmid = {29348212}, issn = {1095-9203}, mesh = {Epidemics/*prevention & control ; History, 20th Century ; Humans ; Influenza Pandemic, 1918-1919/*history ; Influenza Vaccines/immunology ; Influenza, Human/epidemiology/*prevention & control/virology ; Orthomyxoviridae/genetics ; }, } @article {pmid29348211, year = {2018}, author = {Höhr, AIC and Lindau, C and Wirth, C and Qiu, J and Stroud, DA and Kutik, S and Guiard, B and Hunte, C and Becker, T and Pfanner, N and Wiedemann, N}, title = {Membrane protein insertion through a mitochondrial β-barrel gate.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {}, pmid = {29348211}, issn = {1095-9203}, support = {648235//European Research Council/International ; //European Research Council/International ; }, mesh = {Mitochondria/*metabolism ; Mitochondrial Membrane Transport Proteins/genetics/*metabolism ; Mitochondrial Membranes/*metabolism ; Mitochondrial Proteins/chemistry/genetics/*metabolism ; Porins/genetics/*metabolism ; Protein Conformation, beta-Strand ; Protein Folding ; Protein Transport ; Saccharomyces cerevisiae/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/genetics/*metabolism ; Voltage-Dependent Anion Channel 1/genetics/*metabolism ; }, abstract = {The biogenesis of mitochondria, chloroplasts, and Gram-negative bacteria requires the insertion of β-barrel proteins into the outer membranes. Homologous Omp85 proteins are essential for membrane insertion of β-barrel precursors. It is unknown if precursors are threaded through the Omp85-channel interior and exit laterally or if they are translocated into the membrane at the Omp85-lipid interface. We have mapped the interaction of a precursor in transit with the mitochondrial Omp85-channel Sam50 in the native membrane environment. The precursor is translocated into the channel interior, interacts with an internal loop, and inserts into the lateral gate by β-signal exchange. Transport through the Omp85-channel interior followed by release through the lateral gate into the lipid phase may represent a basic mechanism for membrane insertion of β-barrel proteins.}, } @article {pmid29348210, year = {2018}, author = {Lerner, E and Cordes, T and Ingargiola, A and Alhadid, Y and Chung, S and Michalet, X and Weiss, S}, title = {Toward dynamic structural biology: Two decades of single-molecule Förster resonance energy transfer.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {}, pmid = {29348210}, issn = {1095-9203}, support = {R01 GM069709/GM/NIGMS NIH HHS/United States ; R01 GM095904/GM/NIGMS NIH HHS/United States ; }, mesh = {Fluorescence Resonance Energy Transfer/history/*methods ; History, 20th Century ; History, 21st Century ; Molecular Biology/trends ; *Nucleic Acid Conformation ; *Protein Conformation ; Single Molecule Imaging/history/*methods ; }, abstract = {Classical structural biology can only provide static snapshots of biomacromolecules. Single-molecule Förster resonance energy transfer (smFRET) paved the way for studying dynamics in macromolecular structures under biologically relevant conditions. Since its first implementation in 1996, smFRET experiments have confirmed previously hypothesized mechanisms and provided new insights into many fundamental biological processes, such as DNA maintenance and repair, transcription, translation, and membrane transport. We review 22 years of contributions of smFRET to our understanding of basic mechanisms in biochemistry, molecular biology, and structural biology. Additionally, building on current state-of-the-art implementations of smFRET, we highlight possible future directions for smFRET in applications such as biosensing, high-throughput screening, and molecular diagnostics.}, } @article {pmid29348209, year = {2018}, author = {Yang, Z and Yang, S and Yu, P and Li, Y and Doubleday, C and Park, J and Patel, A and Jeon, BS and Russell, WK and Liu, HW and Russell, DH and Houk, KN}, title = {Influence of water and enzyme SpnF on the dynamics and energetics of the ambimodal [6+4]/[4+2] cycloaddition.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E848-E855}, pmid = {29348209}, issn = {1091-6490}, support = {R01 GM040541/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*metabolism ; Catalysis ; Cycloaddition Reaction ; Hydrogen Bonding ; Hydrophobic and Hydrophilic Interactions ; Kinetics ; Macrolides/*metabolism ; Models, Chemical ; Molecular Conformation ; Molecular Dynamics Simulation ; Quantum Theory ; Saccharopolyspora/enzymology ; Software ; Water/*chemistry ; }, abstract = {SpnF is the first monofunctional Diels-Alder/[6+4]-ase that catalyzes a reaction leading to both Diels-Alder and [6+4] adducts through a single transition state. The environment-perturbed transition-state sampling method has been developed to calculate free energies, kinetic isotope effects, and quasi-classical reaction trajectories of enzyme-catalyzed reactions and the uncatalyzed reaction in water. Energetics calculated in this way reproduce the experiment and show that the normal Diels-Alder transition state is stabilized by H bonds with water molecules, while the ambimodal transition state is favored in the enzyme SpnF by both intramolecular hydrogen bonding and hydrophobic binding. Molecular dynamics simulations show that trajectories passing through the ambimodal transition state bifurcate to the [6+4] adduct and the Diels-Alder adduct with a ratio of 1:1 in the gas phase, 1:1.6 in water, and 1:11 in the enzyme. This example shows how an enzyme acts on a vibrational time scale to steer post-transition state trajectories toward the Diels-Alder adduct.}, } @article {pmid29348208, year = {2018}, author = {Sederberg, AJ and MacLean, JN and Palmer, SE}, title = {Learning to make external sensory stimulus predictions using internal correlations in populations of neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1105-1110}, pmid = {29348208}, issn = {1091-6490}, mesh = {Action Potentials/*physiology ; Animals ; Computer Simulation ; Electrodes ; Learning ; *Models, Neurological ; Models, Statistical ; Nerve Net/physiology ; Neural Networks (Computer) ; Neurons/*physiology ; Retina/*physiology ; Retinal Ganglion Cells/*physiology ; Urodela ; Video Recording ; Vision, Ocular ; }, abstract = {To compensate for sensory processing delays, the visual system must make predictions to ensure timely and appropriate behaviors. Recent work has found predictive information about the stimulus in neural populations early in vision processing, starting in the retina. However, to utilize this information, cells downstream must be able to read out the predictive information from the spiking activity of retinal ganglion cells. Here we investigate whether a downstream cell could learn efficient encoding of predictive information in its inputs from the correlations in the inputs themselves, in the absence of other instructive signals. We simulate learning driven by spiking activity recorded in salamander retina. We model a downstream cell as a binary neuron receiving a small group of weighted inputs and quantify the predictive information between activity in the binary neuron and future input. Input weights change according to spike timing-dependent learning rules during a training period. We characterize the readouts learned under spike timing-dependent synaptic update rules, finding that although the fixed points of learning dynamics are not associated with absolute optimal readouts they convey nearly all of the information conveyed by the optimal readout. Moreover, we find that learned perceptrons transmit position and velocity information of a moving-bar stimulus nearly as efficiently as optimal perceptrons. We conclude that predictive information is, in principle, readable from the perspective of downstream neurons in the absence of other inputs. This suggests an important role for feedforward prediction in sensory encoding.}, } @article {pmid29348207, year = {2018}, author = {Gabrielsen, P}, title = {QnAs with Frank S. Bates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1135-1136}, pmid = {29348207}, issn = {1091-6490}, } @article {pmid29348206, year = {2018}, author = {Raney, JR and Compton, BG and Mueller, J and Ober, TJ and Shea, K and Lewis, JA}, title = {Rotational 3D printing of damage-tolerant composites with programmable mechanics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1198-1203}, pmid = {29348206}, issn = {1091-6490}, abstract = {Natural composites exhibit exceptional mechanical performance that often arises from complex fiber arrangements within continuous matrices. Inspired by these natural systems, we developed a rotational 3D printing method that enables spatially controlled orientation of short fibers in polymer matrices solely by varying the nozzle rotation speed relative to the printing speed. Using this method, we fabricated carbon fiber-epoxy composites composed of volume elements (voxels) with programmably defined fiber arrangements, including adjacent regions with orthogonally and helically oriented fibers that lead to nonuniform strain and failure as well as those with purely helical fiber orientations akin to natural composites that exhibit enhanced damage tolerance. Our approach broadens the design, microstructural complexity, and performance space for fiber-reinforced composites through site-specific optimization of their fiber orientation, strain, failure, and damage tolerance.}, } @article {pmid29348205, year = {2018}, author = {Swulius, MT and Nguyen, LT and Ladinsky, MS and Ortega, DR and Aich, S and Mishra, M and Jensen, GJ}, title = {Structure of the fission yeast actomyosin ring during constriction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1455-E1464}, pmid = {29348205}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; P50 GM082545/GM/NIGMS NIH HHS/United States ; R35 GM122588/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Actin Cytoskeleton/*metabolism ; Actins/*metabolism ; Actomyosin/*metabolism ; Cytokinesis/*physiology ; Protein Conformation ; Schizosaccharomyces/growth & development/*metabolism ; Schizosaccharomyces pombe Proteins/*chemistry/*metabolism ; }, abstract = {Cell division in many eukaryotes is driven by a ring containing actin and myosin. While much is known about the main proteins involved, the precise arrangement of actin filaments within the contractile machinery, and how force is transmitted to the membrane, remains unclear. Here we use cryosectioning and cryofocused ion beam milling to gain access to cryopreserved actomyosin rings in Schizosaccharomyces pombe for direct 3D imaging by electron cryotomography. Our results show that straight, overlapping actin filaments, running nearly parallel to each other and to the membrane, form a loose bundle of ∼150 nm in diameter that "saddles" the inward-bending membrane at the leading edge of the division septum. The filaments do not make direct contact with the membrane. Our analysis of the actin filaments reveals the variability in filament number, nearest-neighbor distances between filaments within the bundle, their distance from the membrane, and angular distribution with respect to the membrane.}, } @article {pmid29348204, year = {2018}, author = {Sugioka, K and Fielmich, LE and Mizumoto, K and Bowerman, B and van den Heuvel, S and Kimura, A and Sawa, H}, title = {Tumor suppressor APC is an attenuator of spindle-pulling forces during C. elegans asymmetric cell division.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E954-E963}, pmid = {29348204}, issn = {1091-6490}, support = {P40 OD010440/OD/NIH HHS/United States ; R01 GM049869/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenomatous Polyposis Coli Protein/*metabolism ; Animals ; *Asymmetric Cell Division ; CRISPR-Cas Systems ; Caenorhabditis elegans/*cytology ; Caenorhabditis elegans Proteins/*metabolism ; Cell Cycle Proteins/metabolism ; Cell Polarity ; Centrosome/metabolism ; Computer Simulation ; Cytoplasm/metabolism ; Green Fluorescent Proteins/metabolism ; Microtubules/metabolism ; Models, Theoretical ; Mutation ; RNA Interference ; *Spindle Apparatus ; Stress, Mechanical ; Tubulin/metabolism ; Zygote ; }, abstract = {The adenomatous polyposis coli (APC) tumor suppressor has dual functions in Wnt/β-catenin signaling and accurate chromosome segregation and is frequently mutated in colorectal cancers. Although APC contributes to proper cell division, the underlying mechanisms remain poorly understood. Here we show that Caenorhabditis elegans APR-1/APC is an attenuator of the pulling forces acting on the mitotic spindle. During asymmetric cell division of the C. elegans zygote, a LIN-5/NuMA protein complex localizes dynein to the cell cortex to generate pulling forces on astral microtubules that position the mitotic spindle. We found that APR-1 localizes to the anterior cell cortex in a Par-aPKC polarity-dependent manner and suppresses anterior centrosome movements. Our combined cell biological and mathematical analyses support the conclusion that cortical APR-1 reduces force generation by stabilizing microtubule plus-ends at the cell cortex. Furthermore, APR-1 functions in coordination with LIN-5 phosphorylation to attenuate spindle-pulling forces. Our results document a physical basis for the attenuation of spindle-pulling force, which may be generally used in asymmetric cell division and, when disrupted, potentially contributes to division defects in cancer.}, } @article {pmid29348203, year = {2018}, author = {Yan, J and Grantham, M and Pantelic, J and Bueno de Mesquita, PJ and Albert, B and Liu, F and Ehrman, S and Milton, DK and , }, title = {Infectious virus in exhaled breath of symptomatic seasonal influenza cases from a college community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1081-1086}, pmid = {29348203}, issn = {1091-6490}, support = {RC1 AI086900/AI/NIAID NIH HHS/United States ; }, mesh = {Aerosols ; *Air Microbiology ; Body Mass Index ; Cough ; *Exhalation ; Female ; Humans ; Influenza, Human/*transmission/*virology ; Male ; Models, Theoretical ; Prevalence ; RNA, Viral/genetics ; Respiratory System ; Respiratory Tract Infections/*virology ; Seasons ; Students ; Temperature ; Universities ; Vaccination ; Young Adult ; }, abstract = {Little is known about the amount and infectiousness of influenza virus shed into exhaled breath. This contributes to uncertainty about the importance of airborne influenza transmission. We screened 355 symptomatic volunteers with acute respiratory illness and report 142 cases with confirmed influenza infection who provided 218 paired nasopharyngeal (NP) and 30-minute breath samples (coarse >5-µm and fine ≤5-µm fractions) on days 1-3 after symptom onset. We assessed viral RNA copy number for all samples and cultured NP swabs and fine aerosols. We recovered infectious virus from 52 (39%) of the fine aerosols and 150 (89%) of the NP swabs with valid cultures. The geometric mean RNA copy numbers were 3.8 × 104/30-minutes fine-, 1.2 × 104/30-minutes coarse-aerosol sample, and 8.2 × 108 per NP swab. Fine- and coarse-aerosol viral RNA were positively associated with body mass index and number of coughs and negatively associated with increasing days since symptom onset in adjusted models. Fine-aerosol viral RNA was also positively associated with having influenza vaccination for both the current and prior season. NP swab viral RNA was positively associated with upper respiratory symptoms and negatively associated with age but was not significantly associated with fine- or coarse-aerosol viral RNA or their predictors. Sneezing was rare, and sneezing and coughing were not necessary for infectious aerosol generation. Our observations suggest that influenza infection in the upper and lower airways are compartmentalized and independent.}, } @article {pmid29348202, year = {2018}, author = {Walker, RG and McCoy, JC and Czepnik, M and Mills, MJ and Hagg, A and Walton, KL and Cotton, TR and Hyvönen, M and Lee, RT and Gregorevic, P and Harrison, CA and Thompson, TB}, title = {Molecular characterization of latent GDF8 reveals mechanisms of activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E866-E875}, pmid = {29348202}, issn = {1091-6490}, support = {R01 AG040019/AG/NIA NIH HHS/United States ; R01 AG047131/AG/NIA NIH HHS/United States ; R01 GM114640/GM/NIGMS NIH HHS/United States ; R03 AG049657/AG/NIA NIH HHS/United States ; }, mesh = {Activins/chemistry ; Animals ; Atrophy/pathology ; Cell Differentiation ; Dependovirus ; Growth Differentiation Factors/chemistry ; HEK293 Cells ; Humans ; Hydrogen-Ion Concentration ; Ligands ; Male ; Mice ; Mice, Inbred C57BL ; Mutagenesis ; Mutation ; Myostatin/*chemistry/genetics ; Protein Domains ; Scattering, Small Angle ; Signal Transduction ; Transforming Growth Factor beta/metabolism ; }, abstract = {Growth/differentiation factor 8 (GDF8), or myostatin, negatively regulates muscle mass. GDF8 is held in a latent state through interactions with its N-terminal prodomain, much like TGF-β. Using a combination of small-angle X-ray scattering and mutagenesis, we characterized the interactions of GDF8 with its prodomain. Our results show that the prodomain:GDF8 complex can exist in a fully latent state and an activated or "triggered" state where the prodomain remains in complex with the mature domain. However, these states are not reversible, indicating the latent GDF8 is "spring-loaded." Structural analysis shows that the prodomain:GDF8 complex adopts an "open" configuration, distinct from the latency state of TGF-β and more similar to the open state of Activin A and BMP9 (nonlatent complexes). We determined that GDF8 maintains similar features for latency, including the alpha-1 helix and fastener elements, and identified a series of mutations in the prodomain of GDF8 that alleviate latency, including I56E, which does not require activation by the protease Tolloid. In vivo, active GDF8 variants were potent negative regulators of muscle mass, compared with WT GDF8. Collectively, these results help characterize the latency and activation mechanisms of GDF8.}, } @article {pmid29348201, year = {2018}, author = {Wilburn, DB and Tuttle, LM and Klevit, RE and Swanson, WJ}, title = {Solution structure of sperm lysin yields novel insights into molecular dynamics of rapid protein evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1310-1315}, pmid = {29348201}, issn = {1091-6490}, support = {F32 GM116298/GM/NIGMS NIH HHS/United States ; R01 HD076862/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; *Evolution, Molecular ; Gastropoda/chemistry ; Magnetic Resonance Spectroscopy ; Male ; Models, Molecular ; Molecular Dynamics Simulation ; Mucoproteins/*chemistry/genetics/metabolism ; Mutagenesis, Site-Directed ; Protein Multimerization ; Spermatozoa/*chemistry ; }, abstract = {Protein evolution is driven by the sum of different physiochemical and genetic processes that usually results in strong purifying selection to maintain biochemical functions. However, proteins that are part of systems under arms race dynamics often evolve at unparalleled rates that can produce atypical biochemical properties. In the marine mollusk abalone, lysin and vitelline envelope receptor for lysin (VERL) are a pair of rapidly coevolving proteins that are essential for species-specific interactions between sperm and egg. Despite extensive biochemical characterization of lysin-including crystal structures of multiple orthologs-it was unclear how sites under positive selection may facilitate recognition of VERL. Using a combination of targeted mutagenesis and multidimensional NMR, we present a high-definition solution structure of sperm lysin from red abalone (Haliotis rufescens). Unapparent from the crystallography data, multiple NMR-based analyses conducted in solution reveal clustering of the N and C termini to form a nexus of 13 positively selected sites that constitute a VERL binding interface. Evolutionary rate was found to be a significant predictor of backbone flexibility, which may be critical for lysin bioactivity and/or accelerated evolution. Flexible, rapidly evolving segments that constitute the VERL binding interface were also the most distorted regions of the crystal structure relative to what was observed in solution. While lysin has been the subject of extensive biochemical and evolutionary analyses for more than 30 years, this study highlights the enhanced insights gained from applying NMR approaches to rapidly evolving proteins.}, } @article {pmid29348200, year = {2018}, author = {Melnikov, AA and Poulsen Nautrup, H and Krenn, M and Dunjko, V and Tiersch, M and Zeilinger, A and Briegel, HJ}, title = {Active learning machine learns to create new quantum experiments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1221-1226}, pmid = {29348200}, issn = {1091-6490}, abstract = {How useful can machine learning be in a quantum laboratory? Here we raise the question of the potential of intelligent machines in the context of scientific research. A major motivation for the present work is the unknown reachability of various entanglement classes in quantum experiments. We investigate this question by using the projective simulation model, a physics-oriented approach to artificial intelligence. In our approach, the projective simulation system is challenged to design complex photonic quantum experiments that produce high-dimensional entangled multiphoton states, which are of high interest in modern quantum experiments. The artificial intelligence system learns to create a variety of entangled states and improves the efficiency of their realization. In the process, the system autonomously (re)discovers experimental techniques which are only now becoming standard in modern quantum optical experiments-a trait which was not explicitly demanded from the system but emerged through the process of learning. Such features highlight the possibility that machines could have a significantly more creative role in future research.}, } @article {pmid29348199, year = {2018}, author = {Kim, K and Arora, A and Lewis, RM and Liu, M and Li, W and Shi, AC and Dorfman, KD and Bates, FS}, title = {Origins of low-symmetry phases in asymmetric diblock copolymer melts.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {847-854}, pmid = {29348199}, issn = {1091-6490}, abstract = {Cooling disordered compositionally asymmetric diblock copolymers leads to the formation of nearly spherical particles, each containing hundreds of molecules, which crystallize upon cooling below the order-disorder transition temperature (TODT). Self-consistent field theory (SCFT) reveals that dispersity in the block degrees of polymerization stabilizes various Frank-Kasper phases, including the C14 and C15 Laves phases, which have been accessed experimentally in low-molar-mass poly(isoprene)-b-poly(lactide) (PI-PLA) diblock copolymers using thermal processing strategies. Heating and cooling a specimen containing 15% PLA above and below the TODT from the body-centered cubic (BCC) or C14 states regenerates the same crystalline order established at lower temperatures. This memory effect is also demonstrated with a specimen containing 20% PLA, which recrystallizes to either C15 or hexagonally ordered cylinders (HEXC) upon heating and cooling. The process-path-dependent formation of crystalline order shapes the number of particles per unit volume, n/V, which is retained in the highly structured disordered liquid as revealed by small-angle X-ray scattering (SAXS) experiments. We hypothesize that symmetry breaking during crystallization is governed by the particle number density imprinted in the liquid during ordering at lower temperature, and this metastable liquid is kinetically constrained from equilibrating due to prohibitively large free energy barriers for micelle fusion and fission. Ordering at fixed n/V is enabled by facile chain exchange, which redistributes mass as required to meet the multiple particle sizes and packing associated with specific low-symmetry Frank-Kasper phases. This discovery exposes universal concepts related to order and disorder in self-assembled soft materials.}, } @article {pmid29347979, year = {2018}, author = {Schweikert, LE and Grace, MS}, title = {Altered environmental light drives retinal change in the Atlantic Tarpon (Megalops atlanticus) over timescales relevant to marine environmental disturbance.}, journal = {BMC ecology}, volume = {18}, number = {1}, pages = {1}, pmid = {29347979}, issn = {1472-6785}, support = {2013169376//National Science Foundation/International ; }, abstract = {BACKGROUND: For many fish species, retinal function changes between life history stages as part of an encoded developmental program. Retinal change is also known to exhibit plasticity because retinal form and function can be influenced by light exposure over the course of development. Aside from studies of gene expression, it remains largely unknown whether retinal plasticity can provide functional responses to short-term changes in environmental light quality. The aim of this study was to determine whether the structure and function of the fish retina can change in response to altered light intensity and spectrum-not over the course of a developmental regime, but over shorter time periods relevant to marine habitat disturbance.

RESULTS: The effects of light environment on sensitivity of the retina, as well as on cone photoreceptor distribution were examined in the Atlantic tarpon (Megalops atlanticus) on 2- and 4-month timescales. In a spectral experiment, juvenile M. atlanticus were placed in either 'red' or 'blue' light conditions (with near identical irradiance), and in an intensity experiment, juveniles were placed in either 'bright' or 'dim' light conditions (with near identical spectra). Analysis of the retina by electroretinography and anti-opsin immunofluorescence revealed that relative to fish held in the blue condition, those in the red condition exhibited longer-wavelength peak sensitivity and greater abundance of long-wavelength-sensitive (LWS) cone photoreceptors over time. Following pre-test dark adaption of the retina, fish held in the dim light required less irradiance to produce a standard retinal response than fish held in bright light, developing a greater sensitivity to white light over time.

CONCLUSIONS: The results show that structure and function of the M. atlanticus retina can rapidly adjust to changes in environmental light within a given developmental stage, and that such changes are dependent on light quality and the length of exposure. These findings suggest that the fish retina may be resilient to disturbances in environmental light, using retinal plasticity to compensate for changes in light quality over short timescales.}, } @article {pmid29347977, year = {2018}, author = {Bansal, R and Michel, A}, title = {Expansion of cytochrome P450 and cathepsin genes in the generalist herbivore brown marmorated stink bug.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {60}, pmid = {29347977}, issn = {1471-2164}, mesh = {Amino Acid Sequence ; Animals ; Cathepsins/*genetics ; Cytochrome P-450 Enzyme System/*genetics ; *Gene Regulatory Networks ; *Herbivory ; Heteroptera/*genetics/physiology ; High-Throughput Nucleotide Sequencing ; Insect Proteins/*genetics ; Phylogeny ; Sequence Homology ; Soybeans/growth & development ; Transcriptome ; }, abstract = {BACKGROUND: The brown marmorated stink bug (Halyomorpha halys) is an invasive pest in North America which causes severe economic losses on tree fruits, ornamentals, vegetables, and field crops. The H. halys is an extreme generalist and this feeding behaviour may have been a major contributor behind its establishment and successful adaptation in invasive habitats of North America. To develop an understanding into the mechanism of H. halys' generalist herbivory, here we specifically focused on genes putatively facilitating its adaptation on diverse host plants.

RESULTS: We generated over 142 million reads via sequencing eight RNA-Seq libraries, each representing an individual H. halys adult. The de novo assembly contained 79,855 high quality transcripts, totalling 39,600,178 bases. Following a comprehensive transcriptome analysis, H. halys had an expanded suite of cytochrome P450 and cathepsin-L genes compared to other insects. Detailed characterization of P450 genes from the CYP6 family, known for herbivore adaptation on host plants, strongly hinted towards H. halys-specific expansions involving gene duplications. In subsequent RT-PCR experiments, both P450 and cathepsin genes exhibited tissue-specific or distinct expression patterns which supported their principal roles of detoxification and/or digestion in a particular tissue.

CONCLUSIONS: Our analysis into P450 and cathepsin genes in H. halys offers new insights into potential mechanisms for understanding generalist herbivory and adaptation success in invasive habitats. Additionally, the large-scale transcriptomic resource developed here provides highly useful data for gene discovery; functional, population and comparative genomics as well as efforts to assemble and annotate the H. halys genome.}, } @article {pmid29347972, year = {2018}, author = {Faleye, TOC and Adewumi, MO and Ozegbe, NP and Ogunsakin, OE and Ariyo, G and Adeshina, FW and Ogunga, OS and Oluwadare, SD and Adeniji, JA}, title = {Extending the utility of the WHO recommended assay for direct detection of enteroviruses from clinical specimen for resolving poliovirus co-infection.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {47}, pmid = {29347972}, issn = {1756-0500}, mesh = {Algorithms ; Coinfection/*diagnosis/virology ; Enterovirus/genetics/physiology ; Enterovirus Infections/*diagnosis/virology ; Feces/virology ; Humans ; Poliomyelitis/*diagnosis/virology ; Poliovirus/genetics/physiology ; Polymerase Chain Reaction/*methods ; Population Surveillance/methods ; Reproducibility of Results ; Reverse Transcriptase Polymerase Chain Reaction/*methods ; Sensitivity and Specificity ; World Health Organization ; }, abstract = {OBJECTIVES: In a polio-free world there might be reduced funding for poliovirus surveillance. There is therefore the need to ensure that enterovirologist globally, especially those outside the global polio laboratory network, can participate in poliovirus surveillance without neglecting their enterovirus type of interest. To accomplish this, assays are needed that allow such active participation.

RESULTS: In this study we describes a sensitive and specific utility extension of the recently recommended WHO RT-snPCR assay that enables independent detection of the three poliovirus types especially in cases of co-infection. More importantly, it piggy-backs on the first round PCR product of the WHO recommended assay and consequently ensures that enterovirologists interested in nonpolio enteroviruses can continue their investigations, and contribute significantly and specifically to poliovirus surveillance, by using the excess of their first round PCR product.}, } @article {pmid29347970, year = {2018}, author = {Hassani Idrissi, H and Hmimech, W and Khorb, NE and Akoudad, H and Habbal, R and Nadifi, S}, title = {A synergic effect between CYP2C19*2, CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function alleles is associated with Clopidogrel resistance among Moroccan Acute Coronary Syndromes patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {46}, pmid = {29347970}, issn = {1756-0500}, mesh = {Acute Coronary Syndrome/*drug therapy/genetics ; Aged ; Alleles ; Clopidogrel ; Cytochrome P-450 CYP2C19/*genetics ; Drug Resistance/*genetics ; Female ; Gene Frequency ; *Genetic Variation ; Genotype ; Humans ; Male ; Middle Aged ; Morocco ; Platelet Aggregation Inhibitors/therapeutic use ; Ticlopidine/*analogs & derivatives/therapeutic use ; }, abstract = {OBJECTIVE: The main objective of our study was to investigate the association of CYP2C19*2 and CYP2C19*3 loss-of-function and CYP2C19*17 gain-of-function variants of CYP2C19 gene with Clopidogrel resistance in a sample of Moroccan Acute Coronary Syndromes patients.

RESULTS: Our results showed the existence of a synergic effect between the three alleles, statistically very significant, on Clopidogrel resistance among the treated patients (P = 0.0033). For the three variants of the CYP2C19 gene, the heterozygous and homozygous mutant genotypes were the most frequent among ACS patients (CYP2C19*2: 82.76% GA and 10.35% AA; CYP2C19*3: 76.67% GA and 18.33% AA; CYP2C19*17: 66.67% CT and 18.66% TT). Allelic frequencies were 51.73% vs 48.27% (P < 0.001); 56.67% vs 43.33% (P < 0.001); and 52% vs 48% (P = 0.01) for the mutant and wild type alleles of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 variants respectively. Our results support a role of CYP2C19 gene variants as a potential marker of Clopidogrel response. Understanding the functional and clinical consequences of these variants may help for treating patients more effectively, they could be genetically screened and appropriate dose adjustments could be made on the basis of their CYP2C19 genotype.}, } @article {pmid29347966, year = {2018}, author = {Zhou, W and Gay, N and Oh, J}, title = {ReprDB and panDB: minimalist databases with maximal microbial representation.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {15}, pmid = {29347966}, issn = {2049-2618}, support = {K22 AI119231/AI/NIAID NIH HHS/United States ; }, mesh = {Access to Information ; Algorithms ; Computational Biology/methods ; *Databases, Genetic ; *Gastrointestinal Microbiome ; Humans ; Metagenomics/*methods ; Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {BACKGROUND: Profiling of shotgun metagenomic samples is hindered by a lack of unified microbial reference genome databases that (i) assemble genomic information from all open access microbial genomes, (ii) have relatively small sizes, and (iii) are compatible to various metagenomic read mapping tools. Moreover, computational tools to rapidly compile and update such databases to accommodate the rapid increase in new reference genomes do not exist. As a result, database-guided analyses often fail to profile a substantial fraction of metagenomic shotgun sequencing reads from complex microbiomes.

RESULTS: We report pipelines that efficiently traverse all open access microbial genomes and assemble non-redundant genomic information. The pipelines result in two species-resolution microbial reference databases of relatively small sizes: reprDB, which assembles microbial representative or reference genomes, and panDB, for which we developed a novel iterative alignment algorithm to identify and assemble non-redundant genomic regions in multiple sequenced strains. With the databases, we managed to assign taxonomic labels and genome positions to the majority of metagenomic reads from human skin and gut microbiomes, demonstrating a significant improvement over a previous database-guided analysis on the same datasets.

CONCLUSIONS: reprDB and panDB leverage the rapid increases in the number of open access microbial genomes to more fully profile metagenomic samples. Additionally, the databases exclude redundant sequence information to avoid inflated storage or memory space and indexing or analyzing time. Finally, the novel iterative alignment algorithm significantly increases efficiency in pan-genome identification and can be useful in comparative genomic analyses.}, } @article {pmid29347965, year = {2018}, author = {Feglo, PK and Sewurah, M}, title = {Characterization of highly virulent multidrug resistant Vibrio cholerae isolated from a large cholera outbreak in Ghana.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {45}, pmid = {29347965}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/pharmacology ; Cholera/*epidemiology/microbiology ; Cholera Toxin/genetics ; *Disease Outbreaks ; Drug Resistance, Multiple, Bacterial/*drug effects/genetics ; Genotype ; Ghana/epidemiology ; Humans ; Microbial Sensitivity Tests ; Vibrio cholerae O1/genetics/*isolation & purification/pathogenicity ; Virulence/genetics ; }, abstract = {OBJECTIVE: The purpose of this study was to investigate the virulent factors of Vibrio cholerae which caused an unprecedented large cholera outbreak in Ghana in 2014 and progressed into 2015, affected 28,975 people with 243 deaths.

RESULTS: The V. cholerae isolates were identified to be the classical V. cholerae 01 biotype El Tor, serotype Ogawa, responsible for the large cholera outbreak in Ghana. These El Tor strains bear CtxAB and Tcp virulent genes, making the strains highly virulent. The strains also bear SXT transmissible element coding their resistance to antibiotics, causing high proportions of the strains to be multidrug resistant, with resistant proportions of 95, 90 and 75% to trimethoprim/sulfamethoxazole, ampicillin and ceftriaxone respectively. PFGE patterns indicated that the isolates clustered together with the same pattern and showed clusters similar to strains circulating in DR Congo, Cameroun, Ivory Coast and Togo. The strains carried virulence genes which facilitated the disease causation and spread. This is the first time these virulent genes were determined on the Ghanaian Vibrio strains.}, } @article {pmid29347962, year = {2018}, author = {Zavala, J and Montalvo-Parra, MD and Guerrero-Ramírez, GI and Rodríguez-Barrientos, CA and Treviño, V and Valdez-García, JE}, title = {Primary explant culture and collagen I substrate enhances corneal endothelial cell morphology.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {48}, pmid = {29347962}, issn = {1756-0500}, mesh = {Antigens, CD/genetics ; Cell Culture Techniques/*methods ; Cell Proliferation ; Cells, Cultured ; Collagen ; Collagen Type I/*metabolism ; Drug Combinations ; Endothelial Cells/*cytology/metabolism ; Endothelium, Corneal/*cytology ; Gene Expression ; Glypicans/genetics/metabolism ; Humans ; Immunohistochemistry ; Laminin ; Proteoglycans ; Reverse Transcriptase Polymerase Chain Reaction ; Sodium-Potassium-Exchanging ATPase/metabolism ; Zonula Occludens-1 Protein/genetics ; }, abstract = {OBJECTIVES: Corneal endothelial cell (CEC) isolation and harvest aim to produce engineered grafts to solve donor corneal tissue shortage. To yield high amounts of CEC maintaining morphological and molecular characteristics, several isolation and culture conditions are reported. Here, we combined direct explant culture, with three different coating conditions and a two-step media approach to compare confluence efficiency, morphology, and specific molecular markers expression.

DATA DESCRIPTION: Confluence was reached after 2 weeks in the three coating conditions (Matrigel, collagen I, and in uncoated plates) using a two-step approach (proliferative medium without pituitary extract, followed by stabilizer basal medium). Na/K-ATPase and GPC4 markers were detected by immunocytochemistry while GPC4, CD200, and TJP1 by RT-PCR in the three CEC coating culture conditions. CEC in proliferative medium showed spindle morphology in the three conditions. Polygonal morphology was seen in CEC cultures using basal medium under uncoated and collagen I coated plates. CEC cultured in Matrigel-coated plates remained with spindle morphology in basal medium.}, } @article {pmid29347925, year = {2018}, author = {Moine, F and Brechbühl, J and Nenniger Tosato, M and Beaumann, M and Broillet, MC}, title = {Alarm pheromone and kairomone detection via bitter taste receptors in the mouse Grueneberg ganglion.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {12}, pmid = {29347925}, issn = {1741-7007}, abstract = {BACKGROUND: The mouse Grueneberg ganglion (GG) is an olfactory subsystem specialized in the detection of volatile heterocyclic compounds signalling danger. The signalling pathways transducing the danger signals are only beginning to be characterized.

RESULTS: Screening chemical libraries for compounds structurally resembling the already-identified GG ligands, we found a new category of chemicals previously identified as bitter tastants that initiated fear-related behaviours in mice depending on their volatility and evoked neuronal responses in mouse GG neurons. Screening for the expression of signalling receptors of these compounds in the mouse GG yielded transcripts of the taste receptors Tas2r115, Tas2r131, Tas2r143 and their associated G protein α-gustducin (Gnat3). We were further able to confirm their expression at the protein level. Challenging these three G protein-coupled receptors in a heterologous system with the known GG ligands, we identified TAS2R143 as a chemical danger receptor transducing both alarm pheromone and predator-derived kairomone signals.

CONCLUSIONS: These results demonstrate that similar molecular elements might be used by the GG and by the taste system to detect chemical danger signals present in the environment.}, } @article {pmid29347914, year = {2018}, author = {Feugang, JM and Liao, SF and Willard, ST and Ryan, PL}, title = {In-depth proteomic analysis of boar spermatozoa through shotgun and gel-based methods.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {62}, pmid = {29347914}, issn = {1471-2164}, support = {8-6402-3-018//Agricultural Research Service/International ; }, mesh = {Animals ; Computational Biology ; Electrophoresis, Gel, Two-Dimensional/*methods ; Gene Ontology ; Male ; Mass Spectrometry/*methods ; Proteome/*analysis ; Proteomics/*methods ; Reproduction ; Semen/chemistry ; Seminal Plasma Proteins/*analysis/genetics ; Spermatozoa/*chemistry/cytology ; Swine ; }, abstract = {BACKGROUND: Mature spermatozoa contain numerous epididymal and seminal plasma proteins, which full identification through high-throughput technologies may allow for a better understanding of the sperm biology. Therefore, we conducted a global proteomic analysis of boar spermatozoa through shotgun and gel-based methodologies.

RESULTS: The total proteins were extracted from mature spermatozoa and subjecsted to proteome analyses. Functional analyses of gene ontology representations and pathway enrichments were conducted on the shotgun dataset, followed by immunology and gene expression validations. Shotgun and gel-based approaches allowed the detection of 2728 proteins and 2123 spots, respectively. Approximately 38% and 59% of total proteins were respectively fully and partially annotated, and 3% were unknown. Gene ontology analysis indicated high proportions of proteins associated with intracellular and cytoplasm localizations, protein and nucleic acid binding, hydrolase and transferase activities, and cellular, metabolic, and regulation of biological processes. Proteins associated with phosphorylation processes and mitochondrial membranes, nucleic acid binding, and phosphate and phosphorous metabolics represented 77% of the dataset. Pathways associated with oxidative phosphorylation, citrate cycle, and extra-cellular matrix-receptor interaction were significantly enriched. Protein complex, intracellular organelle, cytoskeletal parts, fertilization and reproduction, and gap junction pathway were significantly enriched within the top 116 highly abundant proteins. Nine randomly selected protein candidates were confirmed with gel-based identification, immunofluorescence detection, and mRNA expression.

CONCLUSIONS: This study offers an in-depth proteomic mapping of mature boar spermatozoa that will enable comparative and discovery research for the improvement of male fertility.}, } @article {pmid29347912, year = {2018}, author = {Zhao, P and Wang, D and Wang, R and Kong, N and Zhang, C and Yang, C and Wu, W and Ma, H and Chen, Q}, title = {Genome-wide analysis of the potato Hsp20 gene family: identification, genomic organization and expression profiles in response to heat stress.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {61}, pmid = {29347912}, issn = {1471-2164}, support = {31500159//National Natural Science Foundation of China (CN)/International ; 2016CXY-05//Science and Technology Innovation Program of Agriculture Department of Shaanxi Province/International ; 2016JQ3029//Natural Science Foundation of Shaanxi Province/International ; 1201610712119//Undergraduate Innovation Foundation of Northwest A&F University/International ; }, mesh = {Chromosome Mapping ; Chromosomes, Plant ; Droughts ; Gene Duplication ; Gene Expression Regulation, Plant ; *Genome, Plant ; Genomics ; HSP20 Heat-Shock Proteins/*genetics ; High-Throughput Nucleotide Sequencing ; Multigene Family ; Phylogeny ; Plant Proteins/*genetics ; Promoter Regions, Genetic ; Solanum tuberosum/*genetics/growth & development ; Stress, Physiological ; *Transcriptome ; }, abstract = {BACKGROUND: Heat shock proteins (Hsps) are essential components in plant tolerance mechanism under various abiotic stresses. Hsp20 is the major family of heat shock proteins, but little of Hsp20 family is known in potato (Solanum tuberosum), which is an important vegetable crop that is thermosensitive.

RESULTS: To reveal the mechanisms of potato Hsp20s coping with abiotic stresses, analyses of the potato Hsp20 gene family were conducted using bioinformatics-based methods. In total, 48 putative potato Hsp20 genes (StHsp20s) were identified and named according to their chromosomal locations. A sequence analysis revealed that most StHsp20 genes (89.6%) possessed no, or only one, intron. A phylogenetic analysis indicated that all of the StHsp20 genes, except 10, were grouped into 12 subfamilies. The 48 StHsp20 genes were randomly distributed on 12 chromosomes. Nineteen tandem duplicated StHsp20s and one pair of segmental duplicated genes (StHsp20-15 and StHsp20-48) were identified. A cis-element analysis inferred that StHsp20s, except for StHsp20-41, possessed at least one stress response cis-element. A heatmap of the StHsp20 gene family showed that the genes, except for StHsp20-2 and StHsp20-45, were expressed in various tissues and organs. Real-time quantitative PCR was used to detect the expression level of StHsp20 genes and demonstrated that the genes responded to multiple abiotic stresses, such as heat, salt or drought stress. The relative expression levels of 14 StHsp20 genes (StHsp20-4, 6, 7, 9, 20, 21, 33, 34, 35, 37, 41, 43, 44 and 46) were significantly up-regulated (more than 100-fold) under heat stress.

CONCLUSIONS: These results provide valuable information for clarifying the evolutionary relationship of the StHsp20 family and in aiding functional characterization of StHsp20 genes in further research.}, } @article {pmid29347911, year = {2018}, author = {Ward, NJ and Green, D and Higgins, J and Dalmay, T and Münsterberg, A and Moxon, S and Wheeler, GN}, title = {microRNAs associated with early neural crest development in Xenopus laevis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {59}, pmid = {29347911}, issn = {1471-2164}, support = {BB/H003525/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBSRC DTP Studentship (BB/J014524/1)//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Base Sequence ; Blastula/cytology/metabolism ; Cells, Cultured ; Embryo, Nonmammalian/*cytology/metabolism ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; MicroRNAs/*genetics ; Neural Crest/*growth & development/metabolism ; Neurogenesis ; Organ Specificity ; Sequence Homology ; Stem Cells/cytology/metabolism ; Xenopus Proteins/genetics/metabolism ; Xenopus laevis/*embryology/genetics ; }, abstract = {BACKGROUND: The neural crest (NC) is a class of transitory stem cell-like cells unique to vertebrate embryos. NC cells arise within the dorsal neural tube where they undergo an epithelial to mesenchymal transition in order to migrate and differentiate throughout the developing embryo. The derivative cell types give rise to multiple tissues, including the craniofacial skeleton, peripheral nervous system and skin pigment cells. Several well-studied gene regulatory networks underpin NC development, which when disrupted can lead to various neurocristopathies such as craniofrontonasal dysplasia, DiGeorge syndrome and some forms of cancer. Small RNAs, such as microRNAs (miRNAs) are non-coding RNA molecules important in post-transcriptional gene silencing and critical for cellular regulation of gene expression.

RESULTS: To uncover novel small RNAs in NC development we used high definition adapters and next generation sequencing of libraries derived from ectodermal explants of Xenopus laevis embryos induced to form neural and NC tissue. Ectodermal and blastula animal pole (blastula) stage tissues were also sequenced. We show that miR-427 is highly abundant in all four tissue types though in an isoform specific manner and we define a set of 11 miRNAs that are enriched in the NC. In addition, we show miR-301a and miR-338 are highly expressed in both the NC and blastula suggesting a role for these miRNAs in maintaining the stem cell-like phenotype of NC cells.

CONCLUSION: We have characterised the miRNAs expressed in Xenopus embryonic explants treated to form ectoderm, neural or NC tissue. This has identified novel tissue specific miRNAs and highlighted differential expression of miR-427 isoforms.}, } @article {pmid29347909, year = {2018}, author = {Wang, B and Liu, H and Liu, Z and Dong, X and Guo, J and Li, W and Chen, J and Gao, C and Zhu, Y and Zheng, X and Chen, Z and Chen, J and Song, W and Hauck, A and Lai, J}, title = {Identification of minor effect QTLs for plant architecture related traits using super high density genotyping and large recombinant inbred population in maize (Zea mays).}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {17}, pmid = {29347909}, issn = {1471-2229}, support = {91435206; 31421005//National Natural Science Foundation of China/International ; 2016YFD0100404; 2016YFD0101803//National Key Technologies Research & Development Program-Seven Major Crops Breeding Project/International ; 2011-G15//948 Project/International ; }, mesh = {Genotyping Techniques/*methods ; Plant Breeding ; *Quantitative Trait Loci ; Zea mays/anatomy & histology/*genetics ; }, abstract = {BACKGROUND: Plant Architecture Related Traits (PATs) are of great importance for maize breeding, and mainly controlled by minor effect quantitative trait loci (QTLs). However, cloning or even fine-mapping of minor effect QTLs is very difficult in maize. Theoretically, large population and high density genetic map can be helpful for increasing QTL mapping resolution and accuracy, but such a possibility have not been actually tested.

RESULTS: Here, we employed a genotyping-by-sequencing (GBS) strategy to construct a linkage map with 16,769 marker bins for 1021 recombinant inbred lines (RILs). Accurately mapping of well studied genes P1, pl1 and r1 underlying silk color demonstrated the map quality. After QTL analysis, a total of 51 loci were mapped for six PATs. Although all of them belong to minor effect alleles, the lengths of the QTL intervals, with a minimum and median of 1.03 and 3.40 Mb respectively, were remarkably reduced as compared with previous reports using smaller size of population or small number of markers. Several genes with known function in maize were shown to be overlapping with or close neighboring to these QTL peaks, including na1, td1, d3 for plant height, ra1 for tassel branch number, and zfl2 for tassel length. To further confirm our mapping results, a plant height QTL, qPH1a, was verified by an introgression lines (ILs).

CONCLUSIONS: We demonstrated a method for high resolution mapping of minor effect QTLs in maize, and the resulted comprehensive QTLs for PATs are valuable for maize molecular breeding in the future.}, } @article {pmid29347906, year = {2018}, author = {Liu, C and Qin, Z and Zhou, X and Xin, M and Wang, C and Liu, D and Li, S}, title = {Expression and functional analysis of the Propamocarb-related gene CsDIR16 in cucumbers.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {16}, pmid = {29347906}, issn = {1471-2229}, support = {31272158//National Natural Science Foundation of China/International ; 31401863//National Natural Science Foundation of China/International ; UNPYSCT-2016007//Young University Innovative Talent Training Program of Heilongjiang Province/International ; }, mesh = {Amino Acid Sequence ; Base Sequence ; Carbamates/*metabolism ; Cucumis sativus/*genetics/metabolism ; Disease Resistance/genetics ; Fungicides, Industrial/*metabolism ; Oomycetes/*physiology ; Plant Diseases/*genetics/microbiology ; Plant Proteins/chemistry/*genetics/metabolism ; }, abstract = {BACKGROUND: Cucumber downy mildew is among the most important diseases that can disrupt cucumber production. Propamocarb, also known as propyl-[3-(dimethylamino)propyl]carbamate (PM), is a systemic carbamate fungicide pesticide that is widely applied in agricultural production because of its high efficiency of pathogens control, especially cucumber downy mildew. However, residual PM can remain in cucumbers after the disease has been controlled. To explore the molecular mechanisms of PM retention, cucumber cultivars 'D9320' (with the highest residual PM content) and 'D0351' (lowest residual PM content) were studied. High-throughput tag-sequencing (Tag-Seq) results showed that the CsDIR16 gene was related to PM residue, which was verified using transgenic technology.

RESULTS: We investigated the activity of a dirigent cucumber protein encoded by the CsDIR16 in gene response to stress induced by PM treatment. Gene-expression levels of CsDIR16 were up-regulated in the fruits, leaves, and stems of 'D0351' plants in response to PM treatment. However, in cultivar 'D9320', CsDIR16 levels were down-regulated in the leaves and stems after PM treatment, with no statistically significant differences observed in the fruits. Induction by jasmonic acid, abscisic acid, polyethylene glycol 4000, NaCl, and Corynespora cassiicola Wei (Cor) resulted in CsDIR16 up-regulation in 'D0351' and 'D9320'. Expression after salicylic acid treatment was up-regulated in 'D0351', but was down-regulated in 'D9320'. CsDIR16 overexpression lowered PM residues, and these were more rapidly reduced in CsDIR16(+) transgenic 'D9320' plants than in wild-type 'D9320' and CsDIR16(-) transgenic plants.

CONCLUSIONS: Analyses of the CsDIR16-expression patterns in the cucumber cultivars with the highest and lowest levels of PM residue, and transgenic validation indicated that CsDIR16 plays a positive role in reducing PM residues. The findings of this study help understand the regulatory mechanisms occurring in response to PM stress in cucumbers and in establishing the genetic basis for developing low-pesticide residue cucumber cultivars.}, } @article {pmid29347841, year = {2018}, author = {Zhang, W and Tang, X and He, X and Chen, G}, title = {Evolutionary Effect on the Embodied Beauty of Landscape Architectures.}, journal = {Evolutionary psychology : an international journal of evolutionary approaches to psychology and behavior}, volume = {16}, number = {1}, pages = {1474704917749742}, doi = {10.1177/1474704917749742}, pmid = {29347841}, issn = {1474-7049}, mesh = {Adolescent ; *Beauty ; *Biological Evolution ; *Esthetics ; Female ; Humans ; *Judgment ; Male ; Visual Perception ; Young Adult ; }, abstract = {According to the framework of evolutionary aesthetics, a sense of beauty is related to environmental adaptation and plasticity of human beings, which has adaptive value and biological foundations. Prior studies have demonstrated that organisms derive benefits from the landscape. In this study, we investigated whether the benefits of landscape might elicit a stronger sense of beauty and what the nature of this sense of beauty is. In two experiments, when viewing classical landscape and nonlandscape architectures photographs, participants rated the aesthetic scores (Experiment 1) and had a two-alternative forced choice aesthetic judgment by pressing the reaction button located near to (15 cm) or far from (45 cm) the presenting stimuli (Experiment 2). The results showed that reaction of aesthetic ratings for classical landscape architectures was faster than those of classical nonlandscape architectures. Furthermore, only the reaction of beautiful judgment of classical landscape architecture photograph was significantly faster when the reaction button was in the near position to the presenting photograph than those in the position of far away from the presenting photograph. This finding suggests a facilitated effect for the aesthetic perception of classical landscape architectures due to their corresponding components including water and green plants with strong evolutionary implications. Furthermore, this sense of beauty for classical landscape architectures might be the embodied approach to beauty based on the viewpoint of evolutionary aesthetics and embodied cognition.}, } @article {pmid29346651, year = {2018}, author = {Corel, E and Méheust, R and Watson, AK and McInerney, JO and Lopez, P and Bapteste, E}, title = {Bipartite Network Analysis of Gene Sharings in the Microbial World.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {899-913}, pmid = {29346651}, issn = {1537-1719}, abstract = {Extensive microbial gene flows affect how we understand virology, microbiology, medical sciences, genetic modification, and evolutionary biology. Phylogenies only provide a narrow view of these gene flows: plasmids and viruses, lacking core genes, cannot be attached to cellular life on phylogenetic trees. Yet viruses and plasmids have a major impact on cellular evolution, affecting both the gene content and the dynamics of microbial communities. Using bipartite graphs that connect up to 149,000 clusters of homologous genes with 8,217 related and unrelated genomes, we can in particular show patterns of gene sharing that do not map neatly with the organismal phylogeny. Homologous genes are recycled by lateral gene transfer, and multiple copies of homologous genes are carried by otherwise completely unrelated (and possibly nested) genomes, that is, viruses, plasmids and prokaryotes. When a homologous gene is present on at least one plasmid or virus and at least one chromosome, a process of "gene externalization," affected by a postprocessed selected functional bias, takes place, especially in Bacteria. Bipartite graphs give us a view of vertical and horizontal gene flow beyond classic taxonomy on a single very large, analytically tractable, graph that goes beyond the cellular Web of Life.}, } @article {pmid29346646, year = {2018}, author = {Pfeifer, SP and Laurent, S and Sousa, VC and Linnen, CR and Foll, M and Excoffier, L and Hoekstra, HE and Jensen, JD}, title = {The Evolutionary History of Nebraska Deer Mice: Local Adaptation in the Face of Strong Gene Flow.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {792-806}, pmid = {29346646}, issn = {1537-1719}, abstract = {The interplay of gene flow, genetic drift, and local selective pressure is a dynamic process that has been well studied from a theoretical perspective over the last century. Wright and Haldane laid the foundation for expectations under an island-continent model, demonstrating that an island-specific beneficial allele may be maintained locally if the selection coefficient is larger than the rate of migration of the ancestral allele from the continent. Subsequent extensions of this model have provided considerably more insight. Yet, connecting theoretical results with empirical data has proven challenging, owing to a lack of information on the relationship between genotype, phenotype, and fitness. Here, we examine the demographic and selective history of deer mice in and around the Nebraska Sand Hills, a system in which variation at the Agouti locus affects cryptic coloration that in turn affects the survival of mice in their local habitat. We first genotyped 250 individuals from 11 sites along a transect spanning the Sand Hills at 660,000 single nucleotide polymorphisms across the genome. Using these genomic data, we found that deer mice first colonized the Sand Hills following the last glacial period. Subsequent high rates of gene flow have served to homogenize the majority of the genome between populations on and off the Sand Hills, with the exception of the Agouti pigmentation locus. Furthermore, mutations at this locus are strongly associated with the pigment traits that are strongly correlated with local soil coloration and thus responsible for cryptic coloration.}, } @article {pmid29346623, year = {2018}, author = {Fakhour, S and Ambroise, J and Renoz, F and Foray, V and Gala, JL and Hance, T}, title = {A large-scale field study of bacterial communities in cereal aphid populations across Morocco.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy003}, pmid = {29346623}, issn = {1574-6941}, abstract = {Insects are frequently associated with bacteria that can have significant ecological and evolutionary impacts on their hosts. To date, few studies have examined the influence of environmental factors to microbiome composition of aphids. The current work assessed the diversity of bacterial communities of five cereal aphid species (Sitobion avenae, Rhopalosiphum padi, R. maidis, Sipha maydis and Diuraphis noxia) collected across Morocco, covering a wide range of environmental conditions. We aimed to test whether symbiont combinations are host or environment specific. Deep 16S rRNA sequencing enabled us to identify 17 bacterial operational taxonomic units (OTUs). The obligate symbiont Buchnera aphidicola was represented by five OTUs with multiple haplotypes in many single samples. Facultative endosymbionts were presented by a high prevalence of Regiella insecticola and Serratia symbiotica in S. avenae and Si. maydis, respectively. In addition to these symbiotic partners, Pseudomonas, Acinetobacter, Pantoea, Erwinia and Staphyloccocus were also identified in aphids, suggesting that the aphid microbiome is not limited to the presence of endosymbiotic bacteria. Beside a significant association between host species and bacterial communities, an inverse correlation was also found between altitude and α-diversity. Overall, our results support that symbiont combinations are mainly host specific.}, } @article {pmid29346618, year = {2018}, author = {Congrains, C and Campanini, EB and Torres, FR and Rezende, VB and Nakamura, AM and de Oliveira, JL and Lima, ALA and Chahad-Ehlers, S and Sobrinho, IS and de Brito, RA}, title = {Evidence of Adaptive Evolution and Relaxed Constraints in Sex-Biased Genes of South American and West Indies Fruit Flies (Diptera: Tephritidae).}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {380-395}, pmid = {29346618}, issn = {1759-6653}, mesh = {Animals ; *Evolution, Molecular ; Female ; Gene Flow ; *Genes, Insect ; Male ; Reproductive Isolation ; Selection, Genetic ; Sex Characteristics ; Tephritidae/*genetics/physiology ; Transcriptome ; }, abstract = {Several studies have demonstrated that genes differentially expressed between sexes (sex-biased genes) tend to evolve faster than unbiased genes, particularly in males. The reason for this accelerated evolution is not clear, but several explanations have involved adaptive and nonadaptive mechanisms. Furthermore, the differences of sex-biased expression patterns of closely related species are also little explored out of Drosophila. To address the evolutionary processes involved with sex-biased expression in species with incipient differentiation, we analyzed male and female transcriptomes of Anastrepha fraterculus and Anastrepha obliqua, a pair of species that have diverged recently, likely in the presence of gene flow. Using these data, we inferred differentiation indexes and evolutionary rates and tested for signals of selection in thousands of genes expressed in head and reproductive transcriptomes from both species. Our results indicate that sex-biased and reproductive-biased genes evolve faster than unbiased genes in both species, which is due to both adaptive pressure and relaxed constraints. Furthermore, among male-biased genes evolving under positive selection, we identified some related to sexual functions such as courtship behavior and fertility. These findings suggest that sex-biased genes may have played important roles in the establishment of reproductive isolation between these species, due to a combination of selection and drift, and unveil a plethora of genetic markers useful for more studies in these species and their differentiation.}, } @article {pmid29346601, year = {2018}, author = {Willi, Y and Fracassetti, M and Zoller, S and Van Buskirk, J}, title = {Accumulation of Mutational Load at the Edges of a Species Range.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {781-791}, doi = {10.1093/molbev/msy003}, pmid = {29346601}, issn = {1537-1719}, abstract = {Why species have geographically restricted distributions is an unresolved question in ecology and evolutionary biology. Here, we test a new explanation that mutation accumulation due to small population size or a history of range expansion can contribute to restricting distributions by reducing population growth rate at the edge. We examined genomic diversity and mutational load across the entire geographic range of the North American plant Arabidopsis lyrata, including old, isolated populations predominantly at the southern edge and regions of postglacial range expansion at the northern and southern edges. Genomic diversity in intergenic regions declined toward distribution edges and signatures of mutational load in exon regions increased. Genomic signatures of mutational load were highly linked to phenotypically expressed load, measured as reduced performance of individual plants and lower estimated rate of population growth. The geographic pattern of load and the connection between load and population growth demonstrate that mutation accumulation reduces fitness at the edge and helps restrict species' distributions.}, } @article {pmid29346588, year = {2018}, author = {Cridland, JM and Ramirez, SR and Dean, CA and Sciligo, A and Tsutsui, ND}, title = {Genome Sequencing of Museum Specimens Reveals Rapid Changes in the Genetic Composition of Honey Bees in California.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {458-472}, pmid = {29346588}, issn = {1759-6653}, support = {S10 RR027303/RR/NCRR NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Bees/*genetics ; California ; Chromosome Mapping ; *Evolution, Molecular ; Genetics, Population ; *Genome, Insect ; Introduced Species ; Metagenomics ; Pollination ; Polymorphism, Single Nucleotide ; Population Dynamics ; }, abstract = {The western honey bee, Apis mellifera, is an enormously influential pollinator in both natural and managed ecosystems. In North America, this species has been introduced numerous times from a variety of different source populations in Europe and Africa. Since then, feral populations have expanded into many different environments across their broad introduced range. Here, we used whole genome sequencing of historical museum specimens and newly collected modern populations from California (USA) to analyze the impact of demography and selection on introduced populations during the past 105 years. We find that populations from both northern and southern California exhibit pronounced genetic changes, but have changed in different ways. In northern populations, honey bees underwent a substantial shift from western European to eastern European ancestry since the 1960s, whereas southern populations are dominated by the introgression of Africanized genomes during the past two decades. Additionally, we identify an isolated island population that has experienced comparatively little change over a large time span. Fine-scale comparison of different populations and time points also revealed SNPs that differ in frequency, highlighting a number of genes that may be important for recent adaptations in these introduced populations.}, } @article {pmid29346541, year = {2018}, author = {Choi, J and Rieke, EL and Moorman, TB and Soupir, ML and Allen, HK and Smith, SD and Howe, A}, title = {Practical implications of erythromycin resistance gene diversity on surveillance and monitoring of resistance.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {4}, pages = {}, pmid = {29346541}, issn = {1574-6941}, abstract = {Use of antibiotics in human and animal medicine has applied selective pressure for the global dissemination of antibiotic-resistant bacteria. Therefore, it is of interest to develop strategies to mitigate the continued amplification and transmission of resistance genes in environmental reservoirs such as farms, hospitals and watersheds. However, the efficacy of mitigation strategies is difficult to evaluate because it is unclear which resistance genes are important to monitor, and which primers to use to detect those genes. Here, we evaluated the diversity of one type of macrolide antibiotic resistance gene (erm) in one type of environment (manure) to determine which primers would be most informative to use in a mitigation study of that environment. We analyzed all known erm genes and assessed the ability of previously published erm primers to detect the diversity. The results showed that all known erm resistance genes group into 66 clusters, and 25 of these clusters (40%) can be targeted with primers found in the literature. These primers can target 74%-85% of the erm gene diversity in the manures analyzed.}, } @article {pmid29346534, year = {2018}, author = {Graham, KE and Prussin, AJ and Marr, LC and Sassoubre, LM and Boehm, AB}, title = {Microbial community structure of sea spray aerosols at three California beaches.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy005}, pmid = {29346534}, issn = {1574-6941}, abstract = {We characterized the microbial communities in sea spray aerosols (SSA), water and sand of three beaches in central California (Cowell Beach, Baker Beach and Lovers Point) by sequencing the V4 region of the 16S rRNA gene. Average concentrations of 16S rRNA genes in SSA ranged from 2.4 × 104 to 1.4 × 105 gene copies per m3 of air. A total of 9781 distinct OTUs were identified in SSA and of these, 1042 OTUs were found in SSA of all beaches. SSA microbial communities included marine taxa, as well as some associated with the terrestrial environment. SSA taxa included organisms that play important roles in biogeochemical cycling of elements such as Planctomyces and Synechococcus, as well as those representing potential pathogens and fecal indicator bacteria including Staphylococcus epidermidis and Enterococcus spp. There were a large number of shared OTUs among SSA and water, and there was relatively high similarity between SSA and water communities. Results are consistent with a conceptual model where SSA is generated by breaking waves and bubble bursting in marine waters and that enables the transport of microorganisms from the sea to sand or other environments.}, } @article {pmid29346532, year = {2018}, author = {Dial, RJ and Ganey, GQ and Skiles, SM}, title = {What color should glacier algae be? An ecological role for red carbon in the cryosphere.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fiy007}, pmid = {29346532}, issn = {1574-6941}, abstract = {Red-colored secondary pigments in glacier algae play an adaptive role in melting snow and ice. We advance this hypothesis using a model of color-based absorption of irradiance, an experiment with colored particles in snow, and the natural history of glacier algae. Carotenoids and phenols-astaxanthin in snow-algae and purpurogallin in ice-algae-shield photosynthetic apparatus by absorbing overabundant visible wavelengths, then dissipating the excess radiant energy as heat. This heat melts proximal ice crystals, providing liquid-water in a 0°C environment and freeing up nutrients bound in frozen water. We show that purple-colored particles transfer 87%-89% of solar energy absorbed by black particles. However, red-colored particles transfer nearly as much (85%-87%) by absorbing peak solar wavelengths and reflecting the visible wavelengths most absorbed by nearby ice and snow crystals; this latter process may reduce potential cellular overheating when snow insulates cells. Blue and green particles transfer only 80%-82% of black particle absorption. In the experiment, red-colored particles melted 87% as much snow as black particles, while blue particles melted 77%. Green-colored snow-algae naturally occupy saturated snow where water is non-limiting; red-colored snow-algae occupy drier, water-limited snow. In addition to increasing melt, we suggest that esterified astaxanthin in snow-alga cells increases hydrophobicity to remain surficial.}, } @article {pmid29346530, year = {2018}, author = {Aguilar, P and Dorador, C and Vila, I and Sommaruga, R}, title = {Bacterioplankton composition in tropical high-elevation lakes of the Andean plateau.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, pmid = {29346530}, issn = {1574-6941}, abstract = {High-elevation lakes in the tropics are subject to extreme environmental fluctuations and microbes may harbor a unique genomic repertoire, but their composition and diversity are largely unknown. Here, we compared the planktonic bacterial community composition (BCC) and diversity of three tropical lakes located in the high Andean plateau (≥4400 m above sea level) during the dry and wet season. Diversity in these lakes was higher in the cool and wet season than in the warm and dry one. Operational taxonomic units (OTUs) composition was significantly different among lakes and between seasons. Members of the class Opitutae, Spartobacteria, Burkholderiales and Actinobacteria were dominant, but only the hgcI clade (Actinobacteria) and the Comamonadaceae family (Burkholderiales) were shared between seasons among the three lakes. In general, a large percentage (up to 42%) of the rare OTUs was unclassified even at the family level. In one lake, a pycnocline and an anoxic water layer with high abundance of Thiocapsa sp. was found in the wet season indicating that the known polymictic thermal condition is not always given. Our study highlights the particular BCC of tropical high-elevation lakes and also how little is known about the variability in physico-chemical conditions of these ecosystems.}, } @article {pmid29345683, year = {2018}, author = {Forster, P}, title = {Homing in on a key factor of climate change.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {288-289}, doi = {10.1038/d41586-018-00480-0}, pmid = {29345683}, issn = {1476-4687}, mesh = {Animals ; *Climate Change ; Ecosystem ; Humans ; }, } @article {pmid29345681, year = {2018}, author = {Ellis, S}, title = {Biotech booms in China.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S19-S22}, doi = {10.1038/d41586-018-00542-3}, pmid = {29345681}, issn = {1476-4687}, mesh = {Biological Science Disciplines/economics/trends ; Biotechnology/*economics/trends ; China ; Drug Discovery/economics/trends ; Drug Industry/economics/trends ; Economic Recession ; Entrepreneurship/economics/organization & administration ; Humans ; Internationality ; Investments ; *Personnel Selection ; Research Personnel/economics ; Translational Medical Research/economics/trends ; Workforce ; }, } @article {pmid29345680, year = {2018}, author = {Powell, K}, title = {Should we steer clear of the winner-takes-all approach?.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {367-369}, doi = {10.1038/d41586-018-00482-y}, pmid = {29345680}, issn = {1476-4687}, } @article {pmid29345679, year = {2018}, author = {Saltelli, A and Stark, P}, title = {Fixing statistics is more than a technical issue.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {281}, doi = {10.1038/d41586-018-00647-9}, pmid = {29345679}, issn = {1476-4687}, } @article {pmid29345678, year = {2018}, author = {}, title = {China needs to listen to its researchers to become a scientific superpower.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {249}, doi = {10.1038/d41586-018-00659-5}, pmid = {29345678}, issn = {1476-4687}, mesh = {Artificial Intelligence/economics/trends ; China ; Humans ; International Cooperation ; Internet/legislation & jurisprudence/statistics & numerical data ; Investments/trends ; Medicine, Chinese Traditional ; Research/economics/instrumentation/*standards/*trends ; *Research Personnel/supply & distribution ; }, } @article {pmid29345677, year = {2018}, author = {Rennie, SM and Platt, ML}, title = {Mice learn to avoid the rat race.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {284-285}, doi = {10.1038/d41586-017-08835-9}, pmid = {29345677}, issn = {1476-4687}, } @article {pmid29345676, year = {2018}, author = {Caro, T and Dall, SRX}, title = {Research kudos does not need a price tag.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {281}, doi = {10.1038/d41586-018-00644-y}, pmid = {29345676}, issn = {1476-4687}, mesh = {*Achievement ; Career Mobility ; Financing, Organized/*economics/*organization & administration ; Research Personnel/*economics/*standards ; Universities/economics ; }, } @article {pmid29345675, year = {2018}, author = {Barany, M}, title = {The Fields Medal should return to its roots.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {271-273}, doi = {10.1038/d41586-018-00513-8}, pmid = {29345675}, issn = {1476-4687}, } @article {pmid29345674, year = {2018}, author = {O'Meara, S}, title = {Career guide: China.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S1}, doi = {10.1038/d41586-018-00535-2}, pmid = {29345674}, issn = {1476-4687}, mesh = {Career Choice ; China ; Gross Domestic Product ; *Personnel Selection ; Science/economics/*trends ; Workforce ; }, } @article {pmid29345673, year = {2018}, author = {Churchill, O}, title = {China's AI dreams.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S10-S12}, doi = {10.1038/d41586-018-00539-y}, pmid = {29345673}, issn = {1476-4687}, } @article {pmid29345672, year = {2018}, author = {Robu, V and Flynn, D and Lane, D}, title = {Train robots to self-certify their safe operation.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {281}, doi = {10.1038/d41586-018-00646-w}, pmid = {29345672}, issn = {1476-4687}, mesh = {*Certification ; Robotics/instrumentation/*methods/*standards ; *Safety ; }, } @article {pmid29345671, year = {2018}, author = {Fullerton, J}, title = {Why an Italian astrophysicist decided to move to Shanghai.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S31}, doi = {10.1038/d41586-018-00549-w}, pmid = {29345671}, issn = {1476-4687}, } @article {pmid29345669, year = {2018}, author = {Hruby, D}, title = {Why China needs your scientific expertise.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S2-S3}, doi = {10.1038/d41586-018-00536-1}, pmid = {29345669}, issn = {1476-4687}, mesh = {China ; Entrepreneurship/statistics & numerical data/trends ; Goals ; Inventions/economics/trends ; Investments ; *Personnel Selection ; Research/economics/*trends ; Research Support as Topic ; Workforce ; }, } @article {pmid29345668, year = {2018}, author = {Jia, H}, title = {The ups and downs of moving to China.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S14-S16}, doi = {10.1038/d41586-018-00540-5}, pmid = {29345668}, issn = {1476-4687}, mesh = {Acculturation ; China/ethnology ; Communication Barriers ; *Emigrants and Immigrants/psychology ; *Internationality ; *Research Personnel/psychology ; }, } @article {pmid29345667, year = {2018}, author = {Rochmyaningsih, D}, title = {Showcase scientists from the global south.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {251}, doi = {10.1038/d41586-018-00662-w}, pmid = {29345667}, issn = {1476-4687}, } @article {pmid29345666, year = {2018}, author = {Van Damme, P}, title = {Limitless translation limits translation.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {289-290}, doi = {10.1038/d41586-017-08785-2}, pmid = {29345666}, issn = {1476-4687}, mesh = {*Gene Expression Regulation ; *Protein Biosynthesis ; Ribosomes ; }, } @article {pmid29345665, year = {2018}, author = {Jia, H}, title = {How to find a job in China.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S4-S7}, doi = {10.1038/d41586-018-00537-0}, pmid = {29345665}, issn = {1476-4687}, mesh = {China ; *Employment/economics ; *Internationality ; *Job Application ; Leadership ; *Personnel Selection/economics/trends ; *Research/economics ; *Research Personnel/economics ; Salaries and Fringe Benefits ; Workforce ; }, } @article {pmid29345664, year = {2018}, author = {Willyard, C}, title = {Could baby's first bacteria take root before birth?.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {264-266}, doi = {10.1038/d41586-018-00664-8}, pmid = {29345664}, issn = {1476-4687}, mesh = {Amniotic Fluid/microbiology ; Animals ; Cesarean Section ; DNA, Bacterial/analysis/*isolation & purification ; Female ; Fetus/immunology/*microbiology ; Germ-Free Life ; Healthy Volunteers ; Humans ; Infant, Newborn ; Meconium/microbiology ; Mice ; *Microbiota ; *Parturition/immunology ; Placenta/immunology/*microbiology ; Pregnancy ; Pregnancy Complications/immunology/microbiology/prevention & control ; Reproducibility of Results ; Uncertainty ; Vagina/microbiology ; }, } @article {pmid29345663, year = {2018}, author = {Racey, PA and Fenton, B and Mubareka, S and Simmons, N and Tuttle, M}, title = {Don't misrepresent link between bats and SARS.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {281}, doi = {10.1038/d41586-018-00603-7}, pmid = {29345663}, issn = {1476-4687}, mesh = {Animals ; *Chiroptera ; Humans ; SARS Virus ; *Severe Acute Respiratory Syndrome ; }, } @article {pmid29345662, year = {2018}, author = {}, title = {Maths strikes a blow for democracy.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {250}, doi = {10.1038/d41586-018-00661-x}, pmid = {29345662}, issn = {1476-4687}, } @article {pmid29345661, year = {2018}, author = {Murphy, F}, title = {How private-sector research is changing China.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S28-S30}, doi = {10.1038/d41586-018-00546-z}, pmid = {29345661}, issn = {1476-4687}, mesh = {Artificial Intelligence/trends ; China ; Cities ; Entrepreneurship/economics/trends ; Internet/economics/statistics & numerical data/trends ; Inventions/*economics/*trends ; Investments ; *Private Sector ; Research/*economics/*trends ; Technology Transfer ; }, } @article {pmid29345660, year = {2018}, author = {Ballard, JD}, title = {Pathogens boosted by food additive.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {285-286}, doi = {10.1038/d41586-017-08775-4}, pmid = {29345660}, issn = {1476-4687}, mesh = {*Food Additives ; Humans ; }, } @article {pmid29345659, year = {2018}, author = {O'Meara, S}, title = {Returning to a revitalized China after research abroad.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S26}, doi = {10.1038/d41586-018-00545-0}, pmid = {29345659}, issn = {1476-4687}, } @article {pmid29345658, year = {2018}, author = {O'Meara, S}, title = {How a biotech entrepreneur benefits from splitting time between China and the United States.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S21}, doi = {10.1038/d41586-018-00543-2}, pmid = {29345658}, issn = {1476-4687}, } @article {pmid29345657, year = {2018}, author = {Hruby, D}, title = {Putting China's science on the map.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S24-S26}, doi = {10.1038/d41586-018-00544-1}, pmid = {29345657}, issn = {1476-4687}, mesh = {Astronomy/standards/trends ; China ; Moon ; Photons ; Quantum Theory ; Research/standards/trends ; Science/*standards/*trends ; Space Flight ; Spacecraft ; Telescopes ; }, } @article {pmid29345656, year = {2018}, author = {}, title = {Intelligence conference, rainforest park and oil-spill fears.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {254-255}, doi = {10.1038/d41586-018-00663-9}, pmid = {29345656}, issn = {1476-4687}, } @article {pmid29345655, year = {2018}, author = {Cyranoski, D}, title = {China enters the battle for AI talent.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {260-261}, doi = {10.1038/d41586-018-00604-6}, pmid = {29345655}, issn = {1476-4687}, } @article {pmid29345654, year = {2018}, author = {Huberman, AD}, title = {Ben Barres (1954-2017).}, journal = {Nature}, volume = {553}, number = {7688}, pages = {282}, doi = {10.1038/d41586-017-08964-1}, pmid = {29345654}, issn = {1476-4687}, mesh = {History, 20th Century ; History, 21st Century ; Mentoring ; Neurobiology/*history ; Neuroglia/cytology/pathology/*physiology ; Transgender Persons/history ; United States ; Women's Rights/history ; }, } @article {pmid29345653, year = {2018}, author = {Zielinska-Dabkowska, KM}, title = {Make lighting healthier.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {274-276}, doi = {10.1038/d41586-018-00568-7}, pmid = {29345653}, issn = {1476-4687}, mesh = {Animal Migration/radiation effects ; Animals ; Circadian Rhythm/physiology/*radiation effects ; Fluorescence ; Health Policy/trends ; Humans ; Insecta/radiation effects ; Lighting/*adverse effects ; Mercury/adverse effects/analysis ; Plant Development/radiation effects ; Public Health/methods/trends ; Risk Assessment ; Rod Opsins/metabolism ; Sleep Initiation and Maintenance Disorders/etiology ; *Sunlight ; }, } @article {pmid29345652, year = {2018}, author = {Gibney, E}, title = {Revamped collider hunts for cracks in the fundamental theory of physics.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {257-258}, doi = {10.1038/d41586-018-00162-x}, pmid = {29345652}, issn = {1476-4687}, } @article {pmid29345651, year = {2018}, author = {Woolston, C}, title = {US immigration fight heightens legal limbo for young 'Dreamer' scientists.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {258-259}, doi = {10.1038/d41586-018-00489-5}, pmid = {29345651}, issn = {1476-4687}, mesh = {Adolescent ; Emigrants and Immigrants/*legislation & jurisprudence ; Emigration and Immigration/*legislation & jurisprudence ; *Federal Government ; Female ; Humans ; Infant ; Politics ; Research Personnel/*legislation & jurisprudence/*psychology ; *Uncertainty ; United States ; Young Adult ; }, } @article {pmid29345650, year = {2018}, author = {Callaway, E}, title = {Synthetic species made to shun sex with wild organisms.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {259-260}, doi = {10.1038/d41586-018-00625-1}, pmid = {29345650}, issn = {1476-4687}, } @article {pmid29345649, year = {2018}, author = {Witze, A}, title = {NASA test proves pulsars can function as a celestial GPS.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {261-262}, doi = {10.1038/d41586-018-00478-8}, pmid = {29345649}, issn = {1476-4687}, } @article {pmid29345648, year = {2018}, author = {Fullerton, J}, title = {Fossilized pregnant dinosaur discovered in southern China.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S15}, doi = {10.1038/d41586-018-00541-4}, pmid = {29345648}, issn = {1476-4687}, mesh = {Animals ; Biological Evolution ; China ; Dinosaurs/*anatomy & histology ; *Fossils ; Pregnancy ; }, } @article {pmid29345647, year = {2018}, author = {}, title = {Laws are not the only way to boost immunization.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {249-250}, doi = {10.1038/d41586-018-00660-y}, pmid = {29345647}, issn = {1476-4687}, mesh = {Child, Preschool ; France ; *Health Policy ; Humans ; Immunity, Herd ; Immunization, Secondary ; Infant ; Measles-Mumps-Rubella Vaccine/administration & dosage/immunology ; Public Health/education/*legislation & jurisprudence/*methods/standards ; *Public Opinion ; Risk Reduction Behavior ; Treatment Adherence and Compliance ; Vaccination/adverse effects/*legislation & jurisprudence/psychology ; Vaccines/*administration & dosage/adverse effects/immunology ; }, } @article {pmid29345646, year = {2018}, author = {Fullerton, J}, title = {Scientists in China regenerate lens in human eye.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S30}, doi = {10.1038/d41586-018-00548-x}, pmid = {29345646}, issn = {1476-4687}, mesh = {China ; Eye ; Humans ; *Lens, Crystalline ; *Regeneration ; }, } @article {pmid29345645, year = {2018}, author = {Ravetz, J}, title = {Integrity must underpin quality of statistics.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {281}, doi = {10.1038/d41586-018-00648-8}, pmid = {29345645}, issn = {1476-4687}, } @article {pmid29345644, year = {2018}, author = {Jia, H}, title = {China's plan to recruit talented researchers.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {S8}, doi = {10.1038/d41586-018-00538-z}, pmid = {29345644}, issn = {1476-4687}, mesh = {China/ethnology ; *Emigration and Immigration ; *Internationality ; *Job Application ; *Personnel Selection ; Research Personnel/economics/*standards ; }, } @article {pmid29345642, year = {2018}, author = {}, title = {Support for US postdocs is growing slowly.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {369}, doi = {10.1038/d41586-018-00559-8}, pmid = {29345642}, issn = {1476-4687}, } @article {pmid29345641, year = {2018}, author = {Irwin, A}, title = {The dark side of light: how artificial lighting is harming the natural world.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {268-270}, doi = {10.1038/d41586-018-00665-7}, pmid = {29345641}, issn = {1476-4687}, mesh = {Animal Diseases/transmission ; Animal Migration ; Animals ; Animals, Wild/physiology ; *Behavior, Animal ; *Darkness ; *Ecosystem ; Female ; Germany ; Humans ; Insecta/physiology ; Lighting/*adverse effects ; Male ; Netherlands ; Plant Development ; Reproduction/physiology ; United Kingdom ; }, } @article {pmid29345640, year = {2018}, author = {Majumdar, S and Devi, LA}, title = {Strategy for making safer opioids bolstered.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {286-288}, doi = {10.1038/d41586-018-00045-1}, pmid = {29345640}, issn = {1476-4687}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {*Analgesics, Opioid ; *Drug Design ; Humans ; *Pain ; }, } @article {pmid29345639, year = {2018}, author = {Cox, PM and Huntingford, C and Williamson, MS}, title = {Emergent constraint on equilibrium climate sensitivity from global temperature variability.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {319-322}, doi = {10.1038/nature25450}, pmid = {29345639}, issn = {1476-4687}, mesh = {Carbon Dioxide/analysis ; Global Warming/history/*statistics & numerical data ; History, 19th Century ; History, 20th Century ; History, 21st Century ; *Models, Theoretical ; Observation ; Probability ; *Temperature ; }, abstract = {Equilibrium climate sensitivity (ECS) remains one of the most important unknowns in climate change science. ECS is defined as the global mean warming that would occur if the atmospheric carbon dioxide (CO2) concentration were instantly doubled and the climate were then brought to equilibrium with that new level of CO2. Despite its rather idealized definition, ECS has continuing relevance for international climate change agreements, which are often framed in terms of stabilization of global warming relative to the pre-industrial climate. However, the 'likely' range of ECS as stated by the Intergovernmental Panel on Climate Change (IPCC) has remained at 1.5-4.5 degrees Celsius for more than 25 years. The possibility of a value of ECS towards the upper end of this range reduces the feasibility of avoiding 2 degrees Celsius of global warming, as required by the Paris Agreement. Here we present a new emergent constraint on ECS that yields a central estimate of 2.8 degrees Celsius with 66 per cent confidence limits (equivalent to the IPCC 'likely' range) of 2.2-3.4 degrees Celsius. Our approach is to focus on the variability of temperature about long-term historical warming, rather than on the warming trend itself. We use an ensemble of climate models to define an emergent relationship between ECS and a theoretically informed metric of global temperature variability. This metric of variability can also be calculated from observational records of global warming, which enables tighter constraints to be placed on ECS, reducing the probability of ECS being less than 1.5 degrees Celsius to less than 3 per cent, and the probability of ECS exceeding 4.5 degrees Celsius to less than 1 per cent.}, } @article {pmid29345638, year = {2018}, author = {Vorländer, MK and Khatter, H and Wetzel, R and Hagen, WJH and Müller, CW}, title = {Molecular mechanism of promoter opening by RNA polymerase III.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {295-300}, pmid = {29345638}, issn = {1476-4687}, support = {340964//European Research Council/International ; }, mesh = {Binding Sites ; Catalytic Domain ; *Cryoelectron Microscopy ; DNA/chemistry/*metabolism/*ultrastructure ; Models, Biological ; Models, Molecular ; *Nucleic Acid Conformation ; *Promoter Regions, Genetic ; Protein Binding ; RNA Polymerase III/chemistry/*metabolism/*ultrastructure ; Saccharomyces cerevisiae/chemistry/ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/metabolism/ultrastructure ; Transcription Factor TFIIIB/chemistry/metabolism/ultrastructure ; Transcription Factors, TFII/chemistry ; Transcription Initiation, Genetic ; }, abstract = {RNA polymerase III (Pol III) and transcription factor IIIB (TFIIIB) assemble together on different promoter types to initiate the transcription of small, structured RNAs. Here we present structures of Pol III preinitiation complexes, comprising the 17-subunit Pol III and the heterotrimeric transcription factor TFIIIB, bound to a natural promoter in different functional states. Electron cryo-microscopy reconstructions, varying from 3.7 Å to 5.5 Å resolution, include two early intermediates in which the DNA duplex is closed, an open DNA complex, and an initially transcribing complex with RNA in the active site. Our structures reveal an extremely tight, multivalent interaction between TFIIIB and promoter DNA, and explain how TFIIIB recruits Pol III. Together, TFIIIB and Pol III subunit C37 activate the intrinsic transcription factor-like activity of the Pol III-specific heterotrimer to initiate the melting of double-stranded DNA, in a mechanism similar to that of the Pol II system.}, } @article {pmid29345637, year = {2018}, author = {Abascal-Palacios, G and Ramsay, EP and Beuron, F and Morris, E and Vannini, A}, title = {Structural basis of RNA polymerase III transcription initiation.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {301-306}, doi = {10.1038/nature25441}, pmid = {29345637}, issn = {1476-4687}, support = {PG/07/076/23480//British Heart Foundation/United Kingdom ; 200818/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Cryoelectron Microscopy ; DNA/chemistry/metabolism/ultrastructure ; Models, Molecular ; Nucleic Acid Conformation ; Promoter Regions, Genetic ; Protein Subunits/chemistry/metabolism ; RNA Polymerase I/chemistry ; RNA Polymerase II/chemistry ; RNA Polymerase III/chemistry/*metabolism/*ultrastructure ; Saccharomyces cerevisiae/chemistry/ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/metabolism/ultrastructure ; Templates, Genetic ; Transcription Factor TFIIIB/chemistry/metabolism/ultrastructure ; Transcription Factors, TFII/chemistry ; *Transcription Initiation, Genetic ; }, abstract = {RNA polymerase (Pol) III transcribes essential non-coding RNAs, including the entire pool of transfer RNAs, the 5S ribosomal RNA and the U6 spliceosomal RNA, and is often deregulated in cancer cells. The initiation of gene transcription by Pol III requires the activity of the transcription factor TFIIIB to form a transcriptionally active Pol III preinitiation complex (PIC). Here we present electron microscopy reconstructions of Pol III PICs at 3.4-4.0 Å and a reconstruction of unbound apo-Pol III at 3.1 Å. TFIIIB fully encircles the DNA and restructures Pol III. In particular, binding of the TFIIIB subunit Bdp1 rearranges the Pol III-specific subunits C37 and C34, thereby promoting DNA opening. The unwound DNA directly contacts both sides of the Pol III cleft. Topologically, the Pol III PIC resembles the Pol II PIC, whereas the Pol I PIC is more divergent. The structures presented unravel the molecular mechanisms underlying the first steps of Pol III transcription and also the general conserved mechanisms of gene transcription initiation.}, } @article {pmid29345312, year = {2018}, author = {Relyea, RA and Stephens, PR and Barrow, LN and Blaustein, AR and Bradley, PW and Buck, JC and Chang, A and Collins, JP and Crother, B and Earl, J and Gervasi, SS and Hoverman, JT and Hyman, O and Lemmon, EM and Luhring, TM and Michelson, M and Murray, C and Price, S and Semlitsch, RD and Sih, A and Stoler, AB and VandenBroek, N and Warwick, A and Wengert, G and Hammond, JI}, title = {Phylogenetic patterns of trait and trait plasticity evolution: Insights from amphibian embryos.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {663-678}, pmid = {29345312}, issn = {1558-5646}, support = {K12 GM088021/GM/NIGMS NIH HHS/United States ; }, abstract = {Environmental variation favors the evolution of phenotypic plasticity. For many species, we understand the costs and benefits of different phenotypes, but we lack a broad understanding of how plastic traits evolve across large clades. Using identical experiments conducted across North America, we examined prey responses to predator cues. We quantified five life-history traits and the magnitude of their plasticity for 23 amphibian species/populations (spanning three families and five genera) when exposed to no cues, crushed-egg cues, and predatory crayfish cues. Embryonic responses varied considerably among species and phylogenetic signal was common among the traits, whereas phylogenetic signal was rare for trait plasticities. Among trait-evolution models, the Ornstein-Uhlenbeck (OU) model provided the best fit or was essentially tied with Brownian motion. Using the best fitting model, evolutionary rates for plasticities were higher than traits for three life-history traits and lower for two. These data suggest that the evolution of life-history traits in amphibian embryos is more constrained by a species' position in the phylogeny than is the evolution of life history plasticities. The fact that an OU model of trait evolution was often a good fit to patterns of trait variation may indicate adaptive optima for traits and their plasticities.}, } @article {pmid29345308, year = {2018}, author = {Seed, CE and Tomkins, JL}, title = {Positive size-speed relationships in gametes and vegetative cells of Chlamydomonas reinhardtii; implications for the evolution of sperm.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {440-452}, doi = {10.1111/evo.13427}, pmid = {29345308}, issn = {1558-5646}, abstract = {It is commonly held that differences in gametes of the two sexes (anisogamy) evolved from ancestors whose gametes were similar in size and behavior (isogamy). Underlying many hypotheses explaining anisogamy are assumed relationships between cell size and speed in the ancestral isogamous population. Using the isogamous alga Chlamydomonas reinhardtii, we explored size-speed distributions in vegetative and gamete cells of 10 cell lines, and clonal data from within two cell lines. We applied an independent speed selection approach to gamete populations of C. reinhardtii, monitoring correlated responses in size following selection for high speed. We demonstrate positive size-speed relationships in clones, cell lines, and artificially selected speed selection lines. We found different size-speed relationships in the two cell types of C. reinhardtii even though they overlap in size, suggesting that cell composition and/or programs of gene expression are capable of altering this relationship, and that the relationship is evolvable. The positive genetic size-speed correlation means that the division of parent vegetative cells into numerous gametes trades off against not only size, but also speed, a trade-off that has not received previous attention. Our results support reevaluating the role of speed selection in the evolution of anisogamy.}, } @article {pmid29345115, year = {2018}, author = {Ji, N and Lin, L and Li, L and Yu, L and Zhang, Y and Luo, H and Li, M and Shi, X and Wang, DZ and Lin, S}, title = {Metatranscriptome analysis reveals environmental and diel regulation of a Heterosigma akashiwo (raphidophyceae) bloom.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1078-1094}, doi = {10.1111/1462-2920.14045}, pmid = {29345115}, issn = {1462-2920}, abstract = {Despite numerous laboratory studies on physiologies of harmful algal bloom (HAB) species, physiologies of these algae during a natural bloom are understudied. Here, we investigated a bloom of the raphidophyte Heterosigma akashiwo in the East China Sea in 2014 using metabarcode (18S rDNA) and metatranscriptome sequencing. Based on 18S rDNA analyses, the phytoplankton community shifted from high diversity in the pre-bloom stage to H. akashiwo predominance during the bloom. A sharp decrease in ambient dissolved inorganic phosphate and strong up-regulation of phosphate and dissolved organic phosphorus (DOP) uptake genes, including the rarely documented (ppGpp)ase, in H. akashiwo from pre-bloom to bloom was indicative of rapid phosphorus uptake and efficient utilization of DOP that might be a driver of the H. akashiwo bloom. Furthermore, observed up-regulated expression of mixotrophy-related genes suggests potential contribution of mixotrophy to the bloom. Accelerating photosynthetic carbon fixation was also implied by the up-regulation of carbonic anhydrase genes during the bloom. Notably, we also observed a strong morning-to-afternoon shift in the expression of many genes. Our findings provide insights into metabolic processes likely important for H. akashiwo bloom formation, and suggest the need to consider timing of sampling in field studies on this alga.}, } @article {pmid29345102, year = {2018}, author = {Martin, E and Varotto Boccazzi, I and De Marco, L and Bongiorno, G and Montagna, M and Sacchi, L and Mensah, P and Ricci, I and Gradoni, L and Bandi, C and Epis, S}, title = {The mycobiota of the sand fly Phlebotomus perniciosus: Involvement of yeast symbionts in uric acid metabolism.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1064-1077}, doi = {10.1111/1462-2920.14044}, pmid = {29345102}, issn = {1462-2920}, abstract = {The knowledge of the fungal mycobiota of arthropods, including the vectors of human and animal diseases, is still limited. Here, the mycobiota associated with the sand fly Phlebotomus perniciosus, the main vector of leishmaniasis in the western Mediterranean area, by a culture-dependent approach (microbiological analyses and sequencing of the 26S rRNA gene), internal transcribed spacer (ITS) rRNA amplicon-based next-generation sequencing, fluorescence in situ hybridisation (FISH), and genome sequencing of the dominant yeast species was investigated. The dominant species was Meyerozyma guilliermondii, known for its biotechnological applications. The focus was on this yeast and its prevalence in adults, pupae and larvae of reared sand flies (overall prevalence: 57.5%) and of field-collected individuals (overall prevalence: 9%) was investigated. Using whole-mount FISH and microscopic examination, it was further showed that M. guilliermondii colonizes the midgut of females, males and larvae and the distal part of Malpighian tubules of female sand flies, suggesting a possible role in urate degradation. Finally, the sequencing and analysis of the genome of M. guilliermondii allowed predicting the complete uric acid degradation pathway, suggesting that the yeast could contribute to the removal of the excess of nitrogenous wastes after the blood meal of the insect host.}, } @article {pmid29345052, year = {2018}, author = {Cui, P and Li, RF and Zhang, DP and Tang, JL and Lu, GT}, title = {HpaP, a novel regulatory protein with ATPase and phosphatase activity, contributes to full virulence in Xanthomonas campestris pv. campestris.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1389-1404}, doi = {10.1111/1462-2920.14046}, pmid = {29345052}, issn = {1462-2920}, abstract = {The ability of the bacterial phytopathogen Xanthomonas campestris pv. campestris (Xcc) to cause disease is dependent on the type III secretion system (T3SS). Proteins of the Xcc T3SS are encoded by hrp (hypersensitive response and pathogenicity) genes and whose expression is mainly controlled by the regulators HrpG and HrpX. Here, we describe the identification and characterization of a previously unknown regulatory protein (named HpaP), which plays important role in hrp gene expression and virulence in Xcc. Clean deletion of hpaP demonstrated reduced virulence and HR (hypersensitive response) induction of Xcc and alterations in cell motility and stress tolerance. Global transcriptome analyses revealed that most hrp genes were down regulated in the hpaP mutant, suggesting HpaP positively regulates hrp genes. GUS activity assays implied that HpaP regulates the expression of hrp genes via controlling the expression of hrpX. Biochemical analyses revealed that HpaP protein had both ATPase and phosphatase activity. While further site-directed mutagenesis of conserved residues in the PTP loop (a protein tyrosine phosphatase signature) of HpaP resulted in the loss of both phosphatase activity and regulatory activity in virulence and HR. Taken together, the findings identify a new regulatory protein that controls hrp gene expression and virulence in Xcc.}, } @article {pmid29345026, year = {2018}, author = {Yang, Y and Dugas, MB and Sudekum, HJ and Murphy, SN and Richards-Zawacki, CL}, title = {Male-male aggression is unlikely to stabilize a poison frog polymorphism.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {457-468}, doi = {10.1111/jeb.13243}, pmid = {29345026}, issn = {1420-9101}, abstract = {Phenotypic polymorphism is common in animals, and the maintenance of multiple phenotypes in a population requires forces that act against homogenizing drift and selection. Male-male competition can contribute to the stability of a polymorphism when males compete primarily with males of the same phenotype. In and around a contact zone between red and blue lineages of the poison frog Oophaga pumilio, we used simulated territorial intrusions to test the nonexclusive predictions that males would direct more aggression towards males of (i) their own phenotype and/or (ii) the phenotype that is most common in their population. Males in the monomorphic red and blue populations that flank the contact zone were more aggressive towards simulated intruders that matched the local coloration. However, males in the two polymorphic populations biased aggression towards neither their own colour nor the colour most common in their population. In sympatry, the rarer colour morph gains no advantage via reduced male-male aggression from territorial males in these O. pumilio populations, and so male aggression seems unlikely to stabilize colour polymorphism on its own. More broadly, these results suggest that the potential for divergent male aggression biases to maintain phenotypic diversity depends on the mechanism(s) that generate the biases and the degree to which these mechanisms persist in sympatry.}, } @article {pmid29345015, year = {2018}, author = {Nielsen, SV and Banks, JL and Diaz, RE and Trainor, PA and Gamble, T}, title = {Dynamic sex chromosomes in Old World chameleons (Squamata: Chamaeleonidae).}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {484-490}, doi = {10.1111/jeb.13242}, pmid = {29345015}, issn = {1420-9101}, abstract = {Much of our current state of knowledge concerning sex chromosome evolution is based on a handful of 'exceptional' taxa with heteromorphic sex chromosomes. However, classifying the sex chromosome systems of additional species lacking easily identifiable, heteromorphic sex chromosomes is indispensable if we wish to fully understand the genesis, degeneration and turnover of vertebrate sex chromosomes. Squamate reptiles (lizards and snakes) are a potential model clade for studying sex chromosome evolution as they exhibit a suite of sex-determining modes yet most species lack heteromorphic sex chromosomes. Only three (of 203) chameleon species have identified sex chromosome systems (all with female heterogamety, ZZ/ZW). This study uses a recently developed method to identify sex-specific genetic markers from restriction site-associated DNA sequence (RADseq) data, which enables the identification of sex chromosome systems in species lacking heteromorphic sex chromosomes. We used RADseq and subsequent PCR validation to identify an XX/XY sex chromosome system in the veiled chameleon (Chamaeleo calyptratus), revealing a novel transition in sex chromosome systems within the Chamaeleonidae. The sex-specific genetic markers identified here will be essential in research focused on sex-specific, comparative, functional and developmental evolutionary questions, further promoting C. calyptratus' utility as an emerging model organism.}, } @article {pmid29345010, year = {2018}, author = {Teets, NM and Hahn, DA}, title = {Genetic variation in the shape of cold-survival curves in a single fly population suggests potential for selection from climate variability.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {543-555}, doi = {10.1111/jeb.13244}, pmid = {29345010}, issn = {1420-9101}, abstract = {Temperature variation is one of the primary challenges facing ectotherms, and the ability to tolerate a range of thermal environments is critical for setting current and future species distributions. Low temperature is particularly challenging for ectotherms because winter conditions have strong latitudinal and temporal variation. Lower lethal temperature (LLT) is a common metric of cold tolerance used in studies of local adaptation and plasticity. Comparisons of LLT across groups typically assume parallel S-shaped survival curves, but genetic variation in the shape of survival vs. temperature curves has not been assessed. Here, we measured the ability of 36 lines of the Drosophila Genetic Reference Panel (DGRP) to survive a 1-h cold shock at seven ecologically relevant low temperatures (-1 to -7 °C) to create a high-resolution response curve for each genotype. We observed surprising variation both in the magnitude of survival and in the shapes of the response curves, with the curves clustering into four distinct shapes. To encompass variation in the shapes of these survival curves, we developed a new cold tolerance metric, cumulative cold tolerance (CCT). By comparing our survival data with climatological data, we propose that variation in the shapes of cold-survival curves arose from weak selection pressure to survive intermediate subzero temperatures in this mid-latitude population of flies. Using publicly available genome sequence and transcript expression data for these lines, we identified several candidate genes associated with CCT, and using transgenic RNAi, we confirmed a functional role for many of these genes.}, } @article {pmid29344709, year = {2018}, author = {de Lima E Silva, MR and Correa, RC and Sakamoto, IK and Varesche, MBA}, title = {Microbial Characterization of Methanogenic and Iron-reducing Consortium in Reactors with Polychlorinated Biphenyls.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {666-676}, pmid = {29344709}, issn = {1432-0991}, mesh = {Bioreactors/*microbiology ; Chloroflexi/metabolism ; Firmicutes/metabolism ; Iron/*metabolism ; Methanol/*metabolism ; Polychlorinated Biphenyls/*metabolism ; Proteobacteria/metabolism ; }, abstract = {Recent papers have confirmed current environmental pollution and the continuous release of polychlorinated biphenyls (PCBs) despite the prohibition of its manufacture worldwide. As the dehalogenating microorganisms are able to remove halogens from various analogous compounds, the characterization of PCB metabolisms can improve the degradation of similar compounds. Thus, this study extensively evaluated the microbial community developed in methanogenic and iron-reducing reactors. The horizontal-flow anaerobic reactor (HAIB) with real waste of Aroclor (1 mL L-1) was fed with mineral medium, ethanol, and sodium formate. Bacteria belonging to Thermotogaceae (Thermotogae), Geobacteraceae, Chloroflexi, Proteobacteria, and Firmicutes (Clostridium) were identified in the HAIB reactor. Bacteria belonging to the Chloroflexi, Firmicutes, and Geobacteraceae are associated with the degradation of hydrocarbons and could be related to the Aroclor waste in this paper. Furthermore, 5.26 × 1012 cells gTVS-1 of iron-reducing bacteria were quantified by the most probable number method in the HAIB reactor, suggesting that this group has an important role in aromatic degradation. Moreover, the evaluation of methanogenic and iron-reducing microorganisms in batch reactors with Aroclor 1260 was performed and the biomass growth was not affected by the addition of PCB. The methane production reached 0.38 µmol CH4 gTVS-1 and the iron reduction attained 90% in batch reactors. Through microbial analyses from HAIB and batch reactors, lower diversity was evidenced in the presence of PCB. This paper indicates the relevant role of iron-reducing organisms and Chloroflexi, Geobacteraceae, and Firmicutes group in PCB metabolism.}, } @article {pmid29344693, year = {2018}, author = {Babbitt, GA and Coppola, EE and Mortensen, JS and Ekeren, PX and Viola, C and Goldblatt, D and Hudson, AO}, title = {Triplet-Based Codon Organization Optimizes the Impact of Synonymous Mutation on Nucleic Acid Molecular Dynamics.}, journal = {Journal of molecular evolution}, volume = {86}, number = {2}, pages = {91-102}, pmid = {29344693}, issn = {1432-1432}, abstract = {Since the elucidation of the genetic code almost 50 years ago, many nonrandom aspects of its codon organization remain only partly resolved. Here, we investigate the recent hypothesis of 'dual-use' codons which proposes that in addition to allowing adjustment of codon optimization to tRNA abundance, the degeneracy in the triplet-based genetic code also multiplexes information regarding DNA's helical shape and protein-binding dynamics while avoiding interference with other protein-level characteristics determined by amino acid properties. How such structural optimization of the code within eukaryotic chromatin could have arisen from an RNA world is a mystery, but would imply some preadaptation in an RNA context. We analyzed synonymous (protein-silent) and nonsynonymous (protein-altering) mutational impacts on molecular dynamics in 13823 identically degenerate alternative codon reorganizations, defined by codon transitions in 7680 GPU-accelerated molecular dynamic simulations of implicitly and explicitly solvated double-stranded aRNA and bDNA structures. When compared to all possible alternative codon assignments, the standard genetic code minimized the impact of synonymous mutations on the random atomic fluctuations and correlations of carbon backbone vector trajectories while facilitating the specific movements that contribute to DNA polymer flexibility. This trend was notably stronger in the context of RNA supporting the idea that dual-use codon optimization and informational multiplexing in DNA resulted from the preadaptation of the RNA duplex to resist changes to thermostability. The nonrandom and divergent molecular dynamics of synonymous mutations also imply that the triplet-based code may have resulted from adaptive functional expansion enabling a primordial doublet code to multiplex gene regulatory information via the shape and charge of the minor groove.}, } @article {pmid29343649, year = {2018}, author = {Tai, JB and Ackerman, PJ and Smalyukh, II}, title = {Topological transformations of Hopf solitons in chiral ferromagnets and liquid crystals.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {921-926}, pmid = {29343649}, issn = {1091-6490}, abstract = {Liquid crystals are widely known for their facile responses to external fields, which forms a basis of the modern information display technology. However, switching of molecular alignment field configurations typically involves topologically trivial structures, although singular line and point defects often appear as short-lived transient states. Here, we demonstrate electric and magnetic switching of nonsingular solitonic structures in chiral nematic and ferromagnetic liquid crystals. These topological soliton structures are characterized by Hopf indices, integers corresponding to the numbers of times that closed-loop-like spatial regions (dubbed "preimages") of two different single orientations of rod-like molecules or magnetization are linked with each other. We show that both dielectric and ferromagnetic response of the studied material systems allow for stabilizing a host of topological solitons with different Hopf indices. The field transformations during such switching are continuous when Hopf indices remain unchanged, even when involving transformations of preimages, but discontinuous otherwise.}, } @article {pmid29343648, year = {2018}, author = {De Ceunynck, K and Peters, CG and Jain, A and Higgins, SJ and Aisiku, O and Fitch-Tewfik, JL and Chaudhry, SA and Dockendorff, C and Parikh, SM and Ingber, DE and Flaumenhaft, R}, title = {PAR1 agonists stimulate APC-like endothelial cytoprotection and confer resistance to thromboinflammatory injury.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E982-E991}, pmid = {29343648}, issn = {1091-6490}, support = {R35 HL135775/HL/NHLBI NIH HHS/United States ; R35 HL139424/HL/NHLBI NIH HHS/United States ; R01 HL112809/HL/NHLBI NIH HHS/United States ; T32 HL116324/HL/NHLBI NIH HHS/United States ; R01 HL093234/HL/NHLBI NIH HHS/United States ; R01 HL125275/HL/NHLBI NIH HHS/United States ; T32 HL007917/HL/NHLBI NIH HHS/United States ; R15 HL127636/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis ; Endothelial Cells/*metabolism ; Factor Xa/metabolism ; Gene Knockdown Techniques ; Glycoproteins/genetics/metabolism ; Human Umbilical Vein Endothelial Cells ; Humans ; Inflammation/*metabolism ; Lipopolysaccharides ; Male ; Mice ; Mice, Inbred C57BL ; Microcirculation ; Peptide Hydrolases/metabolism ; Receptor, PAR-1/*agonists ; Receptors, G-Protein-Coupled/metabolism ; Signal Transduction ; Thrombosis/*metabolism ; Transcription, Genetic ; Up-Regulation ; }, abstract = {Stimulation of protease-activated receptor 1 (PAR1) on endothelium by activated protein C (APC) is protective in several animal models of disease, and APC has been used clinically in severe sepsis and wound healing. Clinical use of APC, however, is limited by its immunogenicity and its anticoagulant activity. We show that a class of small molecules termed "parmodulins" that act at the cytosolic face of PAR1 stimulates APC-like cytoprotective signaling in endothelium. Parmodulins block thrombin generation in response to inflammatory mediators and inhibit platelet accumulation on endothelium cultured under flow. Evaluation of the antithrombotic mechanism showed that parmodulins induce cytoprotective signaling through Gβγ, activating a PI3K/Akt pathway and eliciting a genetic program that includes suppression of NF-κB-mediated transcriptional activation and up-regulation of select cytoprotective transcripts. STC1 is among the up-regulated transcripts, and knockdown of stanniocalin-1 blocks the protective effects of both parmodulins and APC. Induction of this signaling pathway in vivo protects against thromboinflammatory injury in blood vessels. Small-molecule activation of endothelial cytoprotection through PAR1 represents an approach for treatment of thromboinflammatory disease and provides proof-of-principle for the strategy of targeting the cytoplasmic surface of GPCRs to achieve pathway selective signaling.}, } @article {pmid29343647, year = {2018}, author = {Giri Rao, VVH and Gosavi, S}, title = {On the folding of a structurally complex protein to its metastable active state.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {9}, pages = {1998-2003}, pmid = {29343647}, issn = {1091-6490}, mesh = {Catalytic Domain ; Computer Simulation ; Models, Chemical ; Models, Molecular ; Protein Conformation ; *Protein Folding ; alpha 1-Antitrypsin/*chemistry ; }, abstract = {For successful protease inhibition, the reactive center loop (RCL) of the two-domain serine protease inhibitor, α1-antitrypsin (α1-AT), needs to remain exposed in a metastable active conformation. The α1-AT RCL is sequestered in a β-sheet in the stable latent conformation. Thus, to be functional, α1-AT must always fold to a metastable conformation while avoiding folding to a stable conformation. We explore the structural basis of this choice using folding simulations of coarse-grained structure-based models of the two α1-AT conformations. Our simulations capture the key features of folding experiments performed on both conformations. The simulations also show that the free energy barrier to fold to the latent conformation is much larger than the barrier to fold to the active conformation. An entropically stabilized on-pathway intermediate lowers the barrier for folding to the active conformation. In this intermediate, the RCL is in an exposed configuration, and only one of the two α1-AT domains is folded. In contrast, early conversion of the RCL into a β-strand increases the coupling between the two α1-AT domains in the transition state and creates a larger barrier for folding to the latent conformation. Thus, unlike what happens in several proteins, where separate regions promote folding and function, the structure of the RCL, formed early during folding, determines both the conformational and the functional fate of α1-AT. Further, the short 12-residue RCL modulates the free energy barrier and the folding cooperativity of the large 370-residue α1-AT. Finally, we suggest experiments to test the predicted folding mechanism for the latent state.}, } @article {pmid29343646, year = {2018}, author = {Chen, K and Vigliotti, A and Bacca, M and McMeeking, RM and Deshpande, VS and Holmes, JW}, title = {Role of boundary conditions in determining cell alignment in response to stretch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {986-991}, pmid = {29343646}, issn = {1091-6490}, support = {T32 GM008715/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena ; *Cell Physiological Phenomena ; Cells, Cultured ; Collagen ; Fibroblasts/cytology/physiology ; Gels ; Imaging, Three-Dimensional ; Models, Biological ; Rats ; Stress, Mechanical ; }, abstract = {The ability of cells to orient in response to mechanical stimuli is essential to embryonic development, cell migration, mechanotransduction, and other critical physiologic functions in a range of organs. Endothelial cells, fibroblasts, mesenchymal stem cells, and osteoblasts all orient perpendicular to an applied cyclic stretch when plated on stretchable elastic substrates, suggesting a common underlying mechanism. However, many of these same cells orient parallel to stretch in vivo and in 3D culture, and a compelling explanation for the different orientation responses in 2D and 3D has remained elusive. Here, we conducted a series of experiments designed specifically to test the hypothesis that differences in strains transverse to the primary loading direction give rise to the different alignment patterns observed in 2D and 3D cyclic stretch experiments ("strain avoidance"). We found that, in static or low-frequency stretch conditions, cell alignment in fibroblast-populated collagen gels correlated with the presence or absence of a restraining boundary condition rather than with compaction strains. Cyclic stretch could induce perpendicular alignment in 3D culture but only at frequencies an order of magnitude greater than reported to induce perpendicular alignment in 2D. We modified a published model of stress fiber dynamics and were able to reproduce our experimental findings across all conditions tested as well as published data from 2D cyclic stretch experiments. These experimental and model results suggest an explanation for the apparently contradictory alignment responses of cells subjected to cyclic stretch on 2D membranes and in 3D gels.}, } @article {pmid29343645, year = {2018}, author = {Gorelik, A and Illes, K and Nagar, B}, title = {Crystal structure of the mammalian lipopolysaccharide detoxifier.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E896-E905}, pmid = {29343645}, issn = {1091-6490}, support = {P41 GM103485/GM/NIGMS NIH HHS/United States ; MOP-133535//CIHR/Canada ; }, mesh = {Animals ; Calcium/chemistry ; Carboxylic Ester Hydrolases/*chemistry ; Catalytic Domain ; Cell Membrane/metabolism ; Crystallography, X-Ray ; Endosomes/metabolism ; Humans ; Hydrophobic and Hydrophilic Interactions ; Immune System ; Lipopolysaccharides/*chemistry ; Mice ; Protein Binding ; Protein Domains ; Protein Structure, Secondary ; Rabbits ; Saposins/chemistry ; Scattering, Radiation ; Surface Properties ; X-Rays ; }, abstract = {LPS is a potent bacterial endotoxin that triggers the innate immune system. Proper recognition of LPS by pattern-recognition receptors requires a full complement of typically six acyl chains in the lipid portion. Acyloxyacyl hydrolase (AOAH) is a host enzyme that removes secondary (acyloxyacyl-linked) fatty acids from LPS, rendering it immunologically inert. This activity is critical for recovery from immune tolerance that follows Gram-negative infection. To understand the molecular mechanism of AOAH function, we determined its crystal structure and its complex with LPS. The substrate's lipid moiety is accommodated in a large hydrophobic pocket formed by the saposin and catalytic domains with a secondary acyl chain inserted into a narrow lateral hydrophobic tunnel at the active site. The enzyme establishes dispensable contacts with the phosphate groups of LPS but does not interact with its oligosaccharide portion. Proteolytic processing allows movement of an amphipathic helix possibly involved in substrate access at membranes.}, } @article {pmid29343644, year = {2018}, author = {Laencina, L and Dubois, V and Le Moigne, V and Viljoen, A and Majlessi, L and Pritchard, J and Bernut, A and Piel, L and Roux, AL and Gaillard, JL and Lombard, B and Loew, D and Rubin, EJ and Brosch, R and Kremer, L and Herrmann, JL and Girard-Misguich, F}, title = {Identification of genes required for Mycobacterium abscessus growth in vivo with a prominent role of the ESX-4 locus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1002-E1011}, pmid = {29343644}, issn = {1091-6490}, mesh = {Amoeba/*microbiology ; Bacterial Proteins/genetics ; Caspase 1/metabolism ; Chromatography, Thin Layer ; Cytosol/metabolism ; Enzyme Activation ; Flow Cytometry ; Galectin 3/metabolism ; Gene Deletion ; Genomics ; Humans ; Lipids/chemistry ; Macrophages/microbiology ; Mutation ; Mycobacterium abscessus/genetics/*pathogenicity ; Mycobacterium tuberculosis/pathogenicity ; Phagosomes/*microbiology ; THP-1 Cells ; Type IV Secretion Systems/*genetics ; Virulence ; Virulence Factors/*genetics ; }, abstract = {Mycobacterium abscessus, a rapidly growing mycobacterium (RGM) and an opportunistic human pathogen, is responsible for a wide spectrum of clinical manifestations ranging from pulmonary to skin and soft tissue infections. This intracellular organism can resist the bactericidal defense mechanisms of amoebae and macrophages, an ability that has not been observed in other RGM. M. abscessus can up-regulate several virulence factors during transient infection of amoebae, thereby becoming more virulent in subsequent respiratory infections in mice. Here, we sought to identify the M. abscessus genes required for replication within amoebae. To this end, we constructed and screened a transposon (Tn) insertion library of an M. abscessus subspecies massiliense clinical isolate for attenuated clones. This approach identified five genes within the ESX-4 locus, which in M. abscessus encodes an ESX-4 type VII secretion system that exceptionally also includes the ESX conserved EccE component. To confirm the screening results and to get further insight into the contribution of ESX-4 to M. abscessus growth and survival in amoebae and macrophages, we generated a deletion mutant of eccB4 that encodes a core structural element of ESX-4. This mutant was less efficient at blocking phagosomal acidification than its parental strain. Importantly, and in contrast to the wild-type strain, it also failed to damage phagosomes and showed reduced signs of phagosome-to-cytosol contact, as demonstrated by a combination of cellular and immunological assays. This study attributes an unexpected and genuine biological role to the underexplored mycobacterial ESX-4 system and its substrates.}, } @article {pmid29343643, year = {2018}, author = {Huang, Y and Liu, X and Cui, Z and Wiegmann, D and Niro, G and Ducho, C and Song, Y and Yang, Z and Van Lanen, SG}, title = {Pyridoxal-5'-phosphate as an oxygenase cofactor: Discovery of a carboxamide-forming, α-amino acid monooxygenase-decarboxylase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {974-979}, pmid = {29343643}, issn = {1091-6490}, support = {R01 AI087849/AI/NIAID NIH HHS/United States ; R01 AI128862/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Amino Acid Substitution ; Aminoglycosides/chemistry/metabolism ; Anti-Bacterial Agents/chemistry/metabolism ; Bacterial Proteins/genetics/metabolism ; Coenzymes/metabolism ; Genes, Bacterial ; Mixed Function Oxygenases/genetics/metabolism ; Models, Molecular ; Mutagenesis, Site-Directed ; Oxygenases/genetics/*metabolism ; Pyridoxal Phosphate/*metabolism ; Recombinant Proteins/genetics/metabolism ; Sequence Homology, Amino Acid ; }, abstract = {Capuramycins are antimycobacterial antibiotics that consist of a modified nucleoside named uridine-5'-carboxamide (CarU). Previous biochemical studies have revealed that CarU is derived from UMP, which is first converted to uridine-5'-aldehyde in a reaction catalyzed by the dioxygenase CapA and subsequently to 5'-C-glycyluridine (GlyU), an unusual β-hydroxy-α-amino acid, in a reaction catalyzed by the pyridoxal-5'-phosphate (PLP)-dependent transaldolase CapH. The remaining steps that are necessary to furnish CarU include decarboxylation, O atom insertion, and oxidation. We demonstrate that Cap15, which has sequence similarity to proteins annotated as bacterial, PLP-dependent l-seryl-tRNA(Sec) selenium transferases, is the sole catalyst responsible for complete conversion of GlyU to CarU. Using a complementary panel of in vitro assays, Cap15 is shown to be dependent upon substrates O2 and (5'S,6'R)-GlyU, the latter of which was unexpected given that (5'S,6'S)-GlyU is the isomeric product of the transaldolase CapH. The two products of Cap15 are identified as the carboxamide-containing CarU and CO2 While known enzymes that catalyze this type of chemistry, namely α-amino acid 2-monooxygenase, utilize flavin adenine dinucleotide as the redox cofactor, Cap15 remarkably requires only PLP. Furthermore, Cap15 does not produce hydrogen peroxide and is shown to directly incorporate a single O atom from O2 into the product CarU and thus is an authentic PLP-dependent monooxygenase. In addition to these unusual discoveries, Cap15 activity is revealed to be dependent upon the inclusion of phosphate. The biochemical characteristics along with initiatory mechanistic studies of Cap15 are reported, which has allowed us to assign Cap15 as a PLP-dependent (5'S,6'R)-GlyU:O2 monooxygenase-decarboxylase.}, } @article {pmid29343642, year = {2018}, author = {Pan, Y and Yoon, S and Sun, J and Huang, Z and Lee, C and Allen, M and Wu, Y and Chang, YJ and Sadelain, M and Shung, KK and Chien, S and Wang, Y}, title = {Mechanogenetics for the remote and noninvasive control of cancer immunotherapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {992-997}, pmid = {29343642}, issn = {1091-6490}, support = {R01 GM125379/GM/NIGMS NIH HHS/United States ; R33 CA204704/CA/NCI NIH HHS/United States ; T32 HL105373/HL/NHLBI NIH HHS/United States ; R01 HL121365/HL/NHLBI NIH HHS/United States ; K99 GM120493/GM/NIGMS NIH HHS/United States ; R21 CA209629/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Biomechanical Phenomena ; Calcium Signaling ; Genes, Synthetic ; Genetic Engineering ; Genetic Techniques ; HEK293 Cells ; Humans ; Immunotherapy/*methods ; Ion Channels/genetics/immunology ; Jurkat Cells ; Mechanotransduction, Cellular/genetics/immunology ; NFATC Transcription Factors/genetics/metabolism ; Neoplasms/genetics/immunology/*therapy ; Synthetic Biology ; T-Lymphocytes/immunology ; Ultrasonics ; }, abstract = {While cell-based immunotherapy, especially chimeric antigen receptor (CAR)-expressing T cells, is becoming a paradigm-shifting therapeutic approach for cancer treatment, there is a lack of general methods to remotely and noninvasively regulate genetics in live mammalian cells and animals for cancer immunotherapy within confined local tissue space. To address this limitation, we have identified a mechanically sensitive Piezo1 ion channel (mechanosensor) that is activatable by ultrasound stimulation and integrated it with engineered genetic circuits (genetic transducer) in live HEK293T cells to convert the ultrasound-activated Piezo1 into transcriptional activities. We have further engineered the Jurkat T-cell line and primary T cells (peripheral blood mononuclear cells) to remotely sense the ultrasound wave and transduce it into transcriptional activation for the CAR expression to recognize and eradicate target tumor cells. This approach is modular and can be extended for remote-controlled activation of different cell types with high spatiotemporal precision for therapeutic applications.}, } @article {pmid29343641, year = {2018}, author = {Choppara, S and Malonia, SK and Sankaran, G and Green, MR and Santra, MK}, title = {Degradation of FBXO31 by APC/C is regulated by AKT- and ATM-mediated phosphorylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {998-1003}, pmid = {29343641}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Anaphase-Promoting Complex-Cyclosome/antagonists & inhibitors/genetics/*metabolism ; Antigens, CD ; Ataxia Telangiectasia Mutated Proteins/*metabolism ; Cadherins/antagonists & inhibitors/genetics/metabolism ; Cdc20 Proteins/antagonists & inhibitors/genetics/metabolism ; Cell Cycle Checkpoints ; DNA Damage ; F-Box Proteins/chemistry/*metabolism ; Gene Knockdown Techniques ; HEK293 Cells ; Humans ; Models, Biological ; Phosphorylation ; Proteasome Endopeptidase Complex/metabolism ; Proteolysis ; Proto-Oncogene Proteins c-akt/*metabolism ; RNA, Small Interfering/genetics ; Tumor Suppressor Proteins/chemistry/*metabolism ; Ubiquitination ; }, abstract = {The F-box protein FBXO31 is a tumor suppressor that is encoded in 16q24.3, for which there is loss of heterozygosity in various solid tumors. FBXO31 serves as the substrate-recognition component of the SKP/Cullin/F-box protein class of E3 ubiquitin ligases and has been shown to direct degradation of pivotal cell-cycle regulatory proteins including cyclin D1 and the p53 antagonist MDM2. FBXO31 levels are normally low but increase substantially following genotoxic stress through a mechanism that remains to be determined. Here we show that the low levels of FBXO31 are maintained through proteasomal degradation by anaphase-promoting complex/cyclosome (APC/C). We find that the APC/C coactivators CDH1 and CDC20 bind to a destruction-box (D-box) motif present in FBXO31 to promote its polyubiquitination and degradation in a cell-cycle-regulated manner, which requires phosphorylation of FBXO31 on serine-33 by the prosurvival kinase AKT. Following genotoxic stress, phosphorylation of FBXO31 on serine-278 by another kinase, the DNA damage kinase ATM, results in disruption of its interaction with CDH1 and CDC20, thereby preventing FBXO31 degradation. Collectively, our results reveal how alterations in FBXO31 phosphorylation, mediated by AKT and ATM, underlie physiological regulation of FBXO31 levels in unstressed and genotoxically stressed cells.}, } @article {pmid29343640, year = {2018}, author = {Kalish, BT and Cheadle, L and Hrvatin, S and Nagy, MA and Rivera, S and Crow, M and Gillis, J and Kirchner, R and Greenberg, ME}, title = {Single-cell transcriptomics of the developing lateral geniculate nucleus reveals insights into circuit assembly and refinement.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1051-E1060}, pmid = {29343640}, issn = {1091-6490}, support = {R37 NS028829/NS/NINDS NIH HHS/United States ; T32 AG000222/AG/NIA NIH HHS/United States ; R01 MH113005/MH/NIMH NIH HHS/United States ; K12 HD000850/HD/NICHD NIH HHS/United States ; U54 HD090255/HD/NICHD NIH HHS/United States ; F32 MH114501/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Axons/physiology ; Brain/embryology ; Gene Expression Profiling ; *Gene Expression Regulation, Developmental ; Geniculate Bodies/*embryology/*physiology ; Mice ; Microscopy, Electron, Scanning ; Neurogenesis ; Neurons/*physiology ; Retina/physiology ; Sequence Analysis, RNA ; Software ; Synapses/*physiology ; *Transcriptome ; Visual Pathways/physiology ; }, abstract = {Coordinated changes in gene expression underlie the early patterning and cell-type specification of the central nervous system. However, much less is known about how such changes contribute to later stages of circuit assembly and refinement. In this study, we employ single-cell RNA sequencing to develop a detailed, whole-transcriptome resource of gene expression across four time points in the developing dorsal lateral geniculate nucleus (LGN), a visual structure in the brain that undergoes a well-characterized program of postnatal circuit development. This approach identifies markers defining the major LGN cell types, including excitatory relay neurons, oligodendrocytes, astrocytes, microglia, and endothelial cells. Most cell types exhibit significant transcriptional changes across development, dynamically expressing genes involved in distinct processes including retinotopic mapping, synaptogenesis, myelination, and synaptic refinement. Our data suggest that genes associated with synapse and circuit development are expressed in a larger proportion of nonneuronal cell types than previously appreciated. Furthermore, we used this single-cell expression atlas to identify the Prkcd-Cre mouse line as a tool for selective manipulation of relay neurons during a late stage of sensory-driven synaptic refinement. This transcriptomic resource provides a cellular map of gene expression across several cell types of the LGN, and offers insight into the molecular mechanisms of circuit development in the postnatal brain.}, } @article {pmid29343300, year = {2018}, author = {Wirth, JP and Ansumana, R and Woodruff, BA and Koroma, AS and Hodges, MH}, title = {Association between sickle cell and β-thalassemia genes and hemoglobin concentration and anemia in children and non-pregnant women in Sierra Leone: ancillary analysis of data from Sierra Leone's 2013 National Micronutrient Survey.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {43}, pmid = {29343300}, issn = {1756-0500}, support = {HKI-1502//Irish Aid/ ; AID-OAA-A-11-00031//USAID/ ; }, mesh = {Adult ; Anemia/*epidemiology/*genetics ; Anemia, Sickle Cell/*genetics ; Child, Preschool ; Female ; Hemoglobins/*analysis/*genetics ; Humans ; Male ; Sierra Leone/epidemiology ; beta-Thalassemia/*genetics ; }, abstract = {OBJECTIVE: By measuring the associations between the presence of sickle cell and β-thalassemia genes, we assessed the extent to which these hemoglobinopathies contribute to the high prevalence of anemia observed in preschool-aged children and women of reproductive age in Sierra Leone.

RESULTS: The prevalence of anemia was statistically significantly higher in children with homozygous sickle cell genes (HbSS) than in children with normal hemoglobin genes (HbAA or HbAC), but there was no difference in anemia prevalence in those with heterozygous sickle cell trait (HbAS or HbSC) compared with those with normal hemoglobin genes. In women, there was no difference in anemia prevalence by sickle cell status. In both children and women, there was no difference in the anemia prevalence for individuals with or without the β-thalassemia gene. For both sickle cell and β-thalassemia, there was no significant difference in hemoglobin concentrations by sickle cell or β-thalassemia status. Anemia prevalence was higher in children and women with homozygous sickle cell (HbSS). However, as the prevalence of HbSS children (5.4%) and women (1.6%) was quite small, it is unlikely that these hemoglobinopathies substantially contributed to the high anemia prevalence found in the 2013 national micronutrient survey.}, } @article {pmid29343295, year = {2018}, author = {Steinaa, L and Svitek, N and Awino, E and Saya, R and Toye, P}, title = {Cytotoxic T lymphocytes from cattle sharing the same MHC class I haplotype and immunized with live Theileria parva sporozoites differ in antigenic specificity.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {44}, pmid = {29343295}, issn = {1756-0500}, mesh = {Animals ; Antigens, Protozoan/*immunology ; *Cattle/blood/genetics/immunology ; Cattle Diseases/*prevention & control ; Epitopes/*immunology ; Genes, MHC Class I/*genetics ; Haplotypes ; Kenya ; Male ; T-Lymphocytes, Cytotoxic/*immunology ; Theileria parva/*immunology ; Theileriasis/*prevention & control ; }, abstract = {OBJECTIVES: The objective of this study was to assess whether cytotoxic T cells (CTL) generated by the live vaccine, known as "ITM Muguga cocktail", which is used for the cattle disease East Cost fever (ECF) in Sub-Saharan Africa, showed a broad reactivity against many different strains of the causative parasite Theileria parva. We also assessed whether immune responses were similar in cattle expressing the same MHC class I haplotypes.

RESULTS: The antigenic specificity of CTL from MHC class I-matched cattle vaccinated with the Muguga cocktail were different. Three cattle of MHC class I haplotype A18, one A18/A19 and two haploidentical (A18v/A12) animals, showed differential recognition of autologous cells infected with a panel of T. parva isolates. This could have implications in the field where certain strains could break through the vaccine. Furthermore, neither of the haploidentical cattle recognized the CTL epitope (Tp1214-224), presented by the A18 haplotype, in contrast to the third animal, showing differences in immunodominance in animals of the same haplotype A18. This suggests that the CTL specificities following immunization with the Muguga cocktail can vary even between haploidentical individuals and that some parasite strains may break through immunity generated by the Muguga cocktail.}, } @article {pmid29343278, year = {2018}, author = {Abdul-Ghafar, J and Ahmad, Z and Tariq, MU and Kayani, N and Uddin, N}, title = {Lipoblastoma: a clinicopathologic review of 23 cases from a major tertiary care center plus detailed review of literature.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {42}, pmid = {29343278}, issn = {1756-0500}, mesh = {Adolescent ; Child ; Child, Preschool ; Female ; Follow-Up Studies ; Humans ; Infant ; Lipoblastoma/*pathology/surgery ; Male ; Neoplasm Recurrence, Local/*pathology/surgery ; Prognosis ; Tertiary Care Centers ; }, abstract = {OBJECTIVE: Lipoblastoma is a rare neoplasm that occurs mostly in infants and children. Although benign, it has a tendency for local recurrence.

RESULTS: Clinical and pathological features of 23 cases of lipoblastoma described. Patients' age ranged from 8 months to 18 years with mean and median age 4.1 and 2.5 years, respectively. Male:female ratio was 2.8:1. Most common sites were lower extremities (9 cases), followed by abdominal cavity and retroperitoneum (4 cases), and scrotum/groin (3 cases). Grossly, 22 tumors were well circumscribed and multi nodular. All cases showed lobules composed of adipocytes and lipoblasts with intervening fibrous septa and fine vascular network. Myxoid change, capsule formation and septation were seen in all cases. Zonation was seen in 2 cases. Follow-up was available in 14 out of 23 patients. Of these, 13 were alive and free of disease with no evidence of any recurrent lesion. One patient with a mediastinal infiltrating lipoblastoma experienced 4 recurrences. Lipoblastoma is a benign adipocytic neoplasm of infants and young children. Correlation of clinical and histological features helps in reaching a correct diagnosis. Owing to a high recurrence rate following incomplete resection, a complete resection is essential. Prognosis is excellent after complete resection.}, } @article {pmid29343244, year = {2018}, author = {Craig, EA}, title = {Hsp70 at the membrane: driving protein translocation.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {11}, pmid = {29343244}, issn = {1741-7007}, support = {R01 GM027870/GM/NIGMS NIH HHS/United States ; }, abstract = {Efficient movement of proteins across membranes is required for cell health. The translocation process is particularly challenging when the channel in the membrane through which proteins must pass is narrow-such as those in the membranes of the endoplasmic reticulum and mitochondria. Hsp70 molecular chaperones play roles on both sides of these membranes, ensuring efficient translocation of proteins synthesized on cytosolic ribosomes into the interior of these organelles. The "import motor" in the mitochondrial matrix, which is essential for driving the movement of proteins across the mitochondrial inner membrane, is arguably the most complex Hsp70-based system in the cell.}, } @article {pmid29343239, year = {2018}, author = {Gao, W and Xu, FC and Guo, DD and Zhao, JR and Liu, J and Guo, YW and Singh, PK and Ma, XN and Long, L and Botella, JR and Song, CP}, title = {Calcium-dependent protein kinases in cotton: insights into early plant responses to salt stress.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {15}, pmid = {29343239}, issn = {1471-2229}, support = {31601344//National Natural Science Foundation of China/International ; 31701473//National Natural Science Foundation of China/International ; 2016ZX08009-003//Ministry of Agriculture of the People's Republic of China (CN)/International ; 2016YFD0101006//National Key R&D Project for Crop Breeding/International ; }, mesh = {Gene Silencing ; Gossypium/genetics/*physiology ; Multigene Family ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Protein Kinases/*genetics/metabolism ; *Salinity ; Stress, Physiological ; }, abstract = {BACKGROUND: Soil salinization is one of the major environmental constraints to plant growth and agricultural production worldwide. Signaling components involving calcium (Ca2+) and the downstream calcium-dependent protein kinases (CPKs) play key roles in the perception and transduction of stress signals. However, the study of CPKs in cotton and their functions in response to salt stress remain unexplored.

RESULTS: A total of 98 predicted CPKs were identified from upland cotton (Gossypium hirsutum L. 'TM-1'), and phylogenetic analyses classified them into four groups. Gene family distribution studies have revealed the substantial impacts of the genome duplication events to the total number of GhCPKs. Transcriptome analyses showed a wide distribution of CPKs' expression among different organs. A total of 19 CPKs were selected for their rapid responses to salt stress at the transcriptional level, most of which were also incduced by the thylene-releasing chemical ethephon, suggesting a partal overlap of the salinity and ethylene responses. Silencing of 4 of the 19 CPKs (GhCPK8, GhCPK38, GhCPK54, and GhCPK55) severely compromised the basal cotton resistance to salt stress.

CONCLUSIONS: Our genome-wide expression analysis of CPK genes from up-land cotton suggests that CPKs are involved in multiple developmental responses as well as the response to different abiotic stresses. A cluster of the cotton CPKs was shown to participate in the early signaling events in cotton responses to salt stress. Our results provide significant insights on functional analysis of CPKs in cotton, especially in the context of cotton adaptions to salt stress.}, } @article {pmid29343235, year = {2018}, author = {Patel, S and Lu, Z and Jin, X and Swaminathan, P and Zeng, E and Fennell, AY}, title = {Comparison of three assembly strategies for a heterozygous seedless grapevine genome assembly.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {57}, pmid = {29343235}, issn = {1471-2164}, support = {IIA1355423//National Science Foundation/International ; 2011-501181-30635//National Institute of Food and Agriculture/International ; SDRIC//State of South Dakota/International ; }, mesh = {Amino Acid Sequence ; Chromosome Mapping/*methods ; Gene Order ; *Genome, Plant ; Genomics/*methods ; Molecular Sequence Annotation/*methods ; Phylogeny ; Plant Proteins/*genetics ; Polymorphism, Single Nucleotide ; Sequence Homology ; *Transcriptome ; Vitis/classification/*genetics ; }, abstract = {BACKGROUND: De novo heterozygous assembly is an ongoing challenge requiring improved assembly approaches. In this study, three strategies were used to develop de novo Vitis vinifera 'Sultanina' genome assemblies for comparison with the inbred V. vinifera (PN40024 12X.v2) reference genome and a published Sultanina ALLPATHS-LG assembly (AP). The strategies were: 1) a default PLATANUS assembly (PLAT_d) for direct comparison with AP assembly, 2) an iterative merging strategy using METASSEMBLER to combine PLAT_d and AP assemblies (MERGE) and 3) PLATANUS parameter modifications plus GapCloser (PLAT*_GC).

RESULTS: The three new assemblies were greater in size than the AP assembly. PLAT*_GC had the greatest number of scaffolds aligning with a minimum of 95% identity and ≥1000 bp alignment length to V. vinifera (PN40024 12X.v2) reference genome. SNP analysis also identified additional high quality SNPs. A greater number of sequence reads mapped back with zero-mismatch to the PLAT_d, MERGE, and PLAT*_GC (>94%) than was found in the AP assembly (87%) indicating a greater fidelity to the original sequence data in the new assemblies than in AP assembly. A de novo gene prediction conducted using seedless RNA-seq data predicted > 30,000 coding sequences for the three new de novo assemblies, with the greatest number (30,544) in PLAT*_GC and only 26,515 for the AP assembly. Transcription factor analysis indicated good family coverage, but some genes found in the VCOST.v3 annotation were not identified in any of the de novo assemblies, particularly some from the MYB and ERF families.

CONCLUSIONS: The PLAT_d and PLAT*_GC had a greater number of synteny blocks with the V. vinifera (PN40024 12X.v2) reference genome than AP or MERGE. PLAT*_GC provided the most contiguous assembly with only 1.2% scaffold N, in contrast to AP (10.7% N), PLAT_d (6.6% N) and Merge (6.4% N). A PLAT*_GC pseudo-chromosome assembly with chromosome alignment to the reference genome V. vinifera, (PN40024 12X.v2) provides new information for use in seedless grape genetic mapping studies. An annotated de novo gene prediction for the PLAT*_GC assembly, aligned with VitisNet pathways provides new seedless grapevine specific transcriptomic resource that has excellent fidelity with the seedless short read sequence data.}, } @article {pmid29343218, year = {2018}, author = {Cejuela, JM and Vinchurkar, S and Goldberg, T and Prabhu Shankar, MS and Baghudana, A and Bojchevski, A and Uhlig, C and Ofner, A and Raharja-Liu, P and Jensen, LJ and Rost, B}, title = {LocText: relation extraction of protein localizations to assist database curation.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {15}, pmid = {29343218}, issn = {1471-2105}, support = {NNF14CC0001//Novo Nordisk/International ; }, mesh = {*Data Mining ; *Databases, Protein ; Gene Ontology ; Humans ; Molecular Sequence Annotation ; Proteins/*metabolism ; *Software ; }, abstract = {BACKGROUND: The subcellular localization of a protein is an important aspect of its function. However, the experimental annotation of locations is not even complete for well-studied model organisms. Text mining might aid database curators to add experimental annotations from the scientific literature. Existing extraction methods have difficulties to distinguish relationships between proteins and cellular locations co-mentioned in the same sentence.

RESULTS: LocText was created as a new method to extract protein locations from abstracts and full texts. LocText learned patterns from syntax parse trees and was trained and evaluated on a newly improved LocTextCorpus. Combined with an automatic named-entity recognizer, LocText achieved high precision (P = 86%±4). After completing development, we mined the latest research publications for three organisms: human (Homo sapiens), budding yeast (Saccharomyces cerevisiae), and thale cress (Arabidopsis thaliana). Examining 60 novel, text-mined annotations, we found that 65% (human), 85% (yeast), and 80% (cress) were correct. Of all validated annotations, 40% were completely novel, i.e. did neither appear in the annotations nor the text descriptions of Swiss-Prot.

CONCLUSIONS: LocText provides a cost-effective, semi-automated workflow to assist database curators in identifying novel protein localization annotations. The annotations suggested through text-mining would be verified by experts to guarantee high-quality standards of manually-curated databases such as Swiss-Prot.}, } @article {pmid29343217, year = {2018}, author = {Molano, EPL and Cabrera, OG and Jose, J and do Nascimento, LC and Carazzolle, MF and Teixeira, PJPL and Alvarez, JC and Tiburcio, RA and Tokimatu Filho, PM and de Lima, GMA and Guido, RVC and Corrêa, TLR and Leme, AFP and Mieczkowski, P and Pereira, GAG}, title = {Ceratocystis cacaofunesta genome analysis reveals a large expansion of extracellular phosphatidylinositol-specific phospholipase-C genes (PI-PLC).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {58}, pmid = {29343217}, issn = {1471-2164}, support = {2009/50119-9//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 2009/18467-7//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; 142357/2014-6//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; 2013/08293-7//Center for Computational Engineering and Sciences - FAPESP/Cepid/International ; }, mesh = {Ascomycota/*genetics/metabolism ; Cacao/*microbiology ; Evolution, Molecular ; Fungal Proteins/*genetics/metabolism ; *Gene Expression Regulation, Plant ; *Genome, Fungal ; Genomics/*methods ; Phosphatidylinositols/chemistry/metabolism ; Phosphoinositide Phospholipase C/chemistry/*genetics/metabolism ; Phylogeny ; Protein Conformation ; }, abstract = {BACKGROUND: The Ceratocystis genus harbors a large number of phytopathogenic fungi that cause xylem parenchyma degradation and vascular destruction on a broad range of economically important plants. Ceratocystis cacaofunesta is a necrotrophic fungus responsible for lethal wilt disease in cacao. The aim of this work is to analyze the genome of C. cacaofunesta through a comparative approach with genomes of other Sordariomycetes in order to better understand the molecular basis of pathogenicity in the Ceratocystis genus.

RESULTS: We present an analysis of the C. cacaofunesta genome focusing on secreted proteins that might constitute pathogenicity factors. Comparative genome analyses among five Ceratocystidaceae species and 23 other Sordariomycetes fungi showed a strong reduction in gene content of the Ceratocystis genus. However, some gene families displayed a remarkable expansion, in particular, the Phosphatidylinositol specific phospholipases-C (PI-PLC) family. Also, evolutionary rate calculations suggest that the evolution process of this family was guided by positive selection. Interestingly, among the 82 PI-PLCs genes identified in the C. cacaofunesta genome, 70 genes encoding extracellular PI-PLCs are grouped in eight small scaffolds surrounded by transposon fragments and scars that could be involved in the rapid evolution of the PI-PLC family. Experimental secretome using LC-MS/MS validated 24% (86 proteins) of the total predicted secretome (342 proteins), including four PI-PLCs and other important pathogenicity factors.

CONCLUSION: Analysis of the Ceratocystis cacaofunesta genome provides evidence that PI-PLCs may play a role in pathogenicity. Subsequent functional studies will be aimed at evaluating this hypothesis. The observed genetic arsenals, together with the analysis of the PI-PLC family shown in this work, reveal significant differences in the Ceratocystis genome compared to the classical vascular fungi, Verticillium and Fusarium. Altogether, our analyses provide new insights into the evolution and the molecular basis of plant pathogenicity.}, } @article {pmid29342280, year = {2018}, author = {Zoldoš, V and Biruš, I and Muratovic, E and Šatovic, Z and Vojta, A and Robin, O and Pustahija, F and Bogunic, F and Vicic Bockor, V and Siljak-Yakovlev, S}, title = {Epigenetic Differentiation of Natural Populations of Lilium bosniacum Associated with Contrasting Habitat Conditions.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {291-303}, pmid = {29342280}, issn = {1759-6653}, mesh = {Adaptation, Physiological ; Altitude ; Amplified Fragment Length Polymorphism Analysis ; *DNA Methylation ; DNA, Plant/genetics ; DNA, Ribosomal/genetics ; Ecosystem ; *Epigenesis, Genetic ; *Gene Expression Regulation, Plant ; Genetic Loci ; Genetic Variation ; Lilium/*genetics/physiology ; }, abstract = {Epigenetic variation in natural populations with contrasting habitats might be an important element, in addition to the genetic variation, in plant adaptation to environmental stress. Here, we assessed genetic, epigenetic, and cytogenetic structure of the three Lilium bosniacum populations growing on distinct habitats. One population was growing under habitual ecological conditions for this species and the other two were growing under stress associated with high altitude and serpentine soil. Amplified fragment length polymorphism and methylation-sensitive amplification polymorphism analyses revealed that the three populations did not differentiate genetically, but were clearly separated in three distinct clusters according to DNA methylation profiles. Principal coordinate analysis showed that overall epigenetic variation was closely related to habitat conditions. A new methylation-sensitive amplification polymorphism scoring approach allowed identification of mainly unmethylated (φST = 0.190) and fully CpG methylated (φST = 0.118) subepiloci playing a role in overall population differentiation, in comparison with hemimethylated sites (φST = 0.073). In addition, unusual rDNA repatterning and the presence of B chromosomes bearing 5S rDNA loci were recorded in the population growing on serpentine soil, suggesting dynamic chromosome rearrangements probably linked to global genome demethylation, which might have reactivated some mobile elements. We discuss our results considering our earlier data on morphology and leaf anatomy of several L. bosniacum populations, and suggest a possible role of epigenetics as a key element in population differentiation associated with environmental stress in these particular lily populations.}, } @article {pmid29342144, year = {2018}, author = {Surana, NK and Kasper, DL}, title = {Erratum: Moving beyond microbiome-wide associations to causal microbe identification.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {392}, pmid = {29342144}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature25019.}, } @article {pmid29342143, year = {2018}, author = {Vo, LT and Kinney, MA and Liu, X and Zhang, Y and Barragan, J and Sousa, PM and Jha, DK and Han, A and Cesana, M and Shao, Z and North, TE and Orkin, SH and Doulatov, S and Xu, J and Daley, GQ}, title = {Regulation of embryonic haematopoietic multipotency by EZH1.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {506-510}, pmid = {29342143}, issn = {1476-4687}, support = {K99 HL123484/HL/NHLBI NIH HHS/United States ; R24 OD017870/OD/NIH HHS/United States ; U01 HL134812/HL/NHLBI NIH HHS/United States ; R01 DK098241/DK/NIDDK NIH HHS/United States ; P30 DK049216/DK/NIDDK NIH HHS/United States ; U01 HL100001/HL/NHLBI NIH HHS/United States ; U54 DK110805/DK/NIDDK NIH HHS/United States ; R24 DK092760/DK/NIDDK NIH HHS/United States ; /Howard Hughes Medical Institute/Howard Hughes Medical Institute/United States ; R01HL04880/HL/NHLBI NIH HHS/United States ; K01 DK093543/DK/NIDDK NIH HHS/United States ; R00 HL123484/HL/NHLBI NIH HHS/United States ; R01 DK111430/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Cell Lineage ; Chromatin/genetics/metabolism ; Embryonic Development ; Embryonic Stem Cells/*cytology ; Female ; *Gene Silencing ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology ; Humans ; Lymphocytes/*cytology/metabolism ; Mice ; Multipotent Stem Cells/*cytology ; Pluripotent Stem Cells/cytology ; Polycomb Repressive Complex 2/chemistry/deficiency/genetics/*metabolism ; }, abstract = {All haematopoietic cell lineages that circulate in the blood of adult mammals derive from multipotent haematopoietic stem cells (HSCs). By contrast, in the blood of mammalian embryos, lineage-restricted progenitors arise first, independently of HSCs, which only emerge later in gestation. As best defined in the mouse, 'primitive' progenitors first appear in the yolk sac at 7.5 days post-coitum. Subsequently, erythroid-myeloid progenitors that express fetal haemoglobin, as well as fetal lymphoid progenitors, develop in the yolk sac and the embryo proper, but these cells lack HSC potential. Ultimately, 'definitive' HSCs with long-term, multilineage potential and the ability to engraft irradiated adults emerge at 10.5 days post-coitum from arterial endothelium in the aorta-gonad-mesonephros and other haemogenic vasculature. The molecular mechanisms of this reverse progression of haematopoietic ontogeny remain unexplained. We hypothesized that the definitive haematopoietic program might be actively repressed in early embryogenesis through epigenetic silencing, and that alleviating this repression would elicit multipotency in otherwise lineage-restricted haematopoietic progenitors. Here we show that reduced expression of the Polycomb group protein EZH1 enhances multi-lymphoid output from human pluripotent stem cells. In addition, Ezh1 deficiency in mouse embryos results in precocious emergence of functional definitive HSCs in vivo. Thus, we identify EZH1 as a repressor of haematopoietic multipotency in the early mammalian embryo.}, } @article {pmid29342142, year = {2018}, author = {Caggiano, V and Leiras, R and Goñi-Erro, H and Masini, D and Bellardita, C and Bouvier, J and Caldeira, V and Fisone, G and Kiehn, O}, title = {Midbrain circuits that set locomotor speed and gait selection.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {455-460}, pmid = {29342142}, issn = {1476-4687}, support = {693038//European Research Council/International ; R01 NS090919/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Exploratory Behavior ; Gait/*physiology ; Glutamic Acid/metabolism ; Mesencephalon/*cytology/*physiology ; Mice ; Neural Pathways/*physiology ; Neurons/metabolism ; Time Factors ; }, abstract = {Locomotion is a fundamental motor function common to the animal kingdom. It is implemented episodically and adapted to behavioural needs, including exploration, which requires slow locomotion, and escape behaviour, which necessitates faster speeds. The control of these functions originates in brainstem structures, although the neuronal substrate(s) that support them have not yet been elucidated. Here we show in mice that speed and gait selection are controlled by glutamatergic excitatory neurons (GlutNs) segregated in two distinct midbrain nuclei: the cuneiform nucleus (CnF) and the pedunculopontine nucleus (PPN). GlutNs in both of these regions contribute to the control of slower, alternating-gait locomotion, whereas only GlutNs in the CnF are able to elicit high-speed, synchronous-gait locomotion. Additionally, both the activation dynamics and the input and output connectivity matrices of GlutNs in the PPN and the CnF support explorative and escape locomotion, respectively. Our results identify two regions in the midbrain that act in conjunction to select context-dependent locomotor behaviours.}, } @article {pmid29342141, year = {2018}, author = {Pasqual, G and Chudnovskiy, A and Tas, JMJ and Agudelo, M and Schweitzer, LD and Cui, A and Hacohen, N and Victora, GD}, title = {Monitoring T cell-dendritic cell interactions in vivo by intercellular enzymatic labelling.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {496-500}, pmid = {29342141}, issn = {1476-4687}, support = {DP5 OD012146/OD/NIH HHS/United States ; R01 AI119006/AI/NIAID NIH HHS/United States ; }, mesh = {Aminoacyltransferases/metabolism ; Animals ; Bacterial Proteins/metabolism ; CD4 Lymphocyte Count ; CD40 Antigens/immunology/metabolism ; CD40 Ligand/immunology/metabolism ; *Cell Communication ; Cysteine Endopeptidases/metabolism ; Dendritic Cells/*cytology/*immunology ; Female ; Flow Cytometry ; HEK293 Cells ; Humans ; Immunological Synapses/immunology/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Receptors, Antigen, T-Cell/immunology/metabolism ; Staining and Labeling/*methods ; T-Lymphocytes/*cytology/*immunology ; }, abstract = {Interactions between different cell types are essential for multiple biological processes, including immunity, embryonic development and neuronal signalling. Although the dynamics of cell-cell interactions can be monitored in vivo by intravital microscopy, this approach does not provide any information on the receptors and ligands involved or enable the isolation of interacting cells for downstream analysis. Here we describe a complementary approach that uses bacterial sortase A-mediated cell labelling across synapses of immune cells to identify receptor-ligand interactions between cells in living mice, by generating a signal that can subsequently be detected ex vivo by flow cytometry. We call this approach for the labelling of 'kiss-and-run' interactions between immune cells 'Labelling Immune Partnerships by SorTagging Intercellular Contacts' (LIPSTIC). Using LIPSTIC, we show that interactions between dendritic cells and CD4+ T cells during T-cell priming in vivo occur in two distinct modalities: an early, cognate stage, during which CD40-CD40L interactions occur specifically between T cells and antigen-loaded dendritic cells; and a later, non-cognate stage during which these interactions no longer require prior engagement of the T-cell receptor. Therefore, LIPSTIC enables the direct measurement of dynamic cell-cell interactions both in vitro and in vivo. Given its flexibility for use with different receptor-ligand pairs and a range of detectable labels, we expect that this approach will be of use to any field of biology requiring quantification of intercellular communication.}, } @article {pmid29342140, year = {2018}, author = {Diver, MM and Pedi, L and Koide, A and Koide, S and Long, SB}, title = {Atomic structure of the eukaryotic intramembrane RAS methyltransferase ICMT.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {526-529}, pmid = {29342140}, issn = {1476-4687}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; U54 GM087519/GM/NIGMS NIH HHS/United States ; ACB-12002/NH/NIH HHS/United States ; AGM-12006/NH/NIH HHS/United States ; }, mesh = {Animals ; Catalytic Domain ; Coenzymes/chemistry/metabolism ; Crystallography, X-Ray ; Cysteine/analogs & derivatives/chemistry/metabolism ; Drug Design ; Endoplasmic Reticulum/chemistry/metabolism ; Membrane Lipids/chemistry/metabolism ; Models, Molecular ; Protein Methyltransferases/antagonists & inhibitors/*chemistry/*metabolism ; S-Adenosylmethionine/chemistry/metabolism ; Substrate Specificity ; Tribolium/*enzymology ; }, abstract = {The maturation of RAS GTPases and approximately 200 other cellular CAAX proteins involves three enzymatic steps: addition of a farnesyl or geranylgeranyl prenyl lipid to the cysteine (C) in the C-terminal CAAX motif, proteolytic cleavage of the AAX residues and methylation of the exposed prenylcysteine residue at its terminal carboxylate. This final step is catalysed by isoprenylcysteine carboxyl methyltransferase (ICMT), a eukaryote-specific integral membrane enzyme that resides in the endoplasmic reticulum. ICMT is the only cellular enzyme that is known to methylate prenylcysteine substrates; methylation is important for the biological functions of these substrates, such as the membrane localization and subsequent activity of RAS, prelamin A and RAB. Inhibition of ICMT has potential for combating progeria and cancer. Here we present an X-ray structure of ICMT, in complex with its cofactor, an ordered lipid molecule and a monobody inhibitor, at 2.3 Å resolution. The active site spans cytosolic and membrane-exposed regions, indicating distinct entry routes for the cytosolic methyl donor, S-adenosyl-l-methionine, and for prenylcysteine substrates, which are associated with the endoplasmic reticulum membrane. The structure suggests how ICMT overcomes the topographical challenge and unfavourable energetics of bringing two reactants that have different cellular localizations together in a membrane environment-a relatively uncharacterized but defining feature of many integral membrane enzymes.}, } @article {pmid29342139, year = {2018}, author = {Dai, X and Gong, D and Lim, H and Jih, J and Wu, TT and Sun, R and Zhou, ZH}, title = {Structure and mutagenesis reveal essential capsid protein interactions for KSHV replication.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {521-525}, pmid = {29342139}, issn = {1476-4687}, support = {1U24GM116792/NH/NIH HHS/United States ; R01 AI094386/AI/NIAID NIH HHS/United States ; UL1 TR000124/TR/NCATS NIH HHS/United States ; CA177322/NH/NIH HHS/United States ; S10 OD018111/OD/NIH HHS/United States ; CA091791/NH/NIH HHS/United States ; U24 GM116792/GM/NIGMS NIH HHS/United States ; R01 GM071940/GM/NIGMS NIH HHS/United States ; DE025567/NH/NIH HHS/United States ; R01 DE025567/DE/NIDCR NIH HHS/United States ; GM071940/NH/NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; 1S10OD018111/NH/NIH HHS/United States ; AI094386/NH/NIH HHS/United States ; P01 CA177322/CA/NCI NIH HHS/United States ; R01 CA091791/CA/NCI NIH HHS/United States ; }, mesh = {Capsid/chemistry/metabolism/ultrastructure ; Capsid Proteins/chemistry/*genetics/*metabolism/ultrastructure ; *Cryoelectron Microscopy ; Disulfides/metabolism ; Drug Design ; Herpesvirus 8, Human/chemistry/genetics/*growth & development/*ultrastructure ; Hydrophobic and Hydrophilic Interactions ; Models, Molecular ; *Mutagenesis ; Mutant Proteins/chemistry/genetics/metabolism/ultrastructure ; Mutation ; Protein Binding ; Protein Domains ; Protein Multimerization ; Protein Stability ; *Virus Replication/genetics ; }, abstract = {Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma, a cancer that commonly affects patients with AIDS and which is endemic in sub-Saharan Africa. The KSHV capsid is highly pressurized by its double-stranded DNA genome, as are the capsids of the eight other human herpesviruses. Capsid assembly and genome packaging of herpesviruses are prone to interruption and can therefore be targeted for the structure-guided development of antiviral agents. However, herpesvirus capsids-comprising nearly 3,000 proteins and over 1,300 Å in diameter-present a formidable challenge to atomic structure determination and functional mapping of molecular interactions. Here we report a 4.2 Å resolution structure of the KSHV capsid, determined by electron-counting cryo-electron microscopy, and its atomic model, which contains 46 unique conformers of the major capsid protein (MCP), the smallest capsid protein (SCP) and the triplex proteins Tri1 and Tri2. Our structure and mutagenesis results reveal a groove in the upper domain of the MCP that contains hydrophobic residues that interact with the SCP, which in turn crosslinks with neighbouring MCPs in the same hexon to stabilize the capsid. Multiple levels of MCP-MCP interaction-including six sets of stacked hairpins lining the hexon channel, disulfide bonds across channel and buttress domains in neighbouring MCPs, and an interaction network forged by the N-lasso domain and secured by the dimerization domain-define a robust capsid that is resistant to the pressure exerted by the enclosed genome. The triplexes, each composed of two Tri2 molecules and a Tri1 molecule, anchor to the capsid floor via a Tri1 N-anchor to plug holes in the MCP network and rivet the capsid floor. These essential roles of the MCP N-lasso and Tri1 N-anchor are verified by serial-truncation mutageneses. Our proof-of-concept demonstration of the use of polypeptides that mimic the smallest capsid protein to inhibit KSHV lytic replication highlights the potential for exploiting the interaction hotspots revealed in our atomic structure to develop antiviral agents.}, } @article {pmid29342138, year = {2018}, author = {Chen, G and Liu, Y and Goetz, R and Fu, L and Jayaraman, S and Hu, MC and Moe, OW and Liang, G and Li, X and Mohammadi, M}, title = {α-Klotho is a non-enzymatic molecular scaffold for FGF23 hormone signalling.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {461-466}, pmid = {29342138}, issn = {1476-4687}, support = {P30 DK079328/DK/NIDDK NIH HHS/United States ; R01 DE013686/DE/NIDCR NIH HHS/United States ; R01 DK091392/DK/NIDDK NIH HHS/United States ; R01 DK092461/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Binding Sites/genetics ; Body Fluids/metabolism ; Female ; Fibroblast Growth Factors/*chemistry/genetics/*metabolism ; Glucuronidase/*chemistry/genetics/*metabolism ; Heparitin Sulfate/metabolism ; Humans ; Ligands ; Male ; Mice ; Models, Molecular ; Multiprotein Complexes/chemistry/genetics/metabolism ; Mutation ; *Paracrine Communication ; Protein Binding ; Protein Domains ; Protein Multimerization ; Receptor, Fibroblast Growth Factor, Type 1/*chemistry/*metabolism ; *Signal Transduction ; Solubility ; }, abstract = {The ageing suppressor α-klotho binds to the fibroblast growth factor receptor (FGFR). This commits FGFR to respond to FGF23, a key hormone in the regulation of mineral ion and vitamin D homeostasis. The role and mechanism of this co-receptor are unknown. Here we present the atomic structure of a 1:1:1 ternary complex that consists of the shed extracellular domain of α-klotho, the FGFR1c ligand-binding domain, and FGF23. In this complex, α-klotho simultaneously tethers FGFR1c by its D3 domain and FGF23 by its C-terminal tail, thus implementing FGF23-FGFR1c proximity and conferring stability. Dimerization of the stabilized ternary complexes and receptor activation remain dependent on the binding of heparan sulfate, a mandatory cofactor of paracrine FGF signalling. The structure of α-klotho is incompatible with its purported glycosidase activity. Thus, shed α-klotho functions as an on-demand non-enzymatic scaffold protein that promotes FGF23 signalling.}, } @article {pmid29342137, year = {2018}, author = {Zabala-Letona, A and Arruabarrena-Aristorena, A and Martín-Martín, N and Fernandez-Ruiz, S and Sutherland, JD and Clasquin, M and Tomas-Cortazar, J and Jimenez, J and Torres, I and Quang, P and Ximenez-Embun, P and Bago, R and Ugalde-Olano, A and Loizaga-Iriarte, A and Lacasa-Viscasillas, I and Unda, M and Torrano, V and Cabrera, D and van Liempd, SM and Cendon, Y and Castro, E and Murray, S and Revandkar, A and Alimonti, A and Zhang, Y and Barnett, A and Lein, G and Pirman, D and Cortazar, AR and Arreal, L and Prudkin, L and Astobiza, I and Valcarcel-Jimenez, L and Zuñiga-García, P and Fernandez-Dominguez, I and Piva, M and Caro-Maldonado, A and Sánchez-Mosquera, P and Castillo-Martín, M and Serra, V and Beraza, N and Gentilella, A and Thomas, G and Azkargorta, M and Elortza, F and Farràs, R and Olmos, D and Efeyan, A and Anguita, J and Muñoz, J and Falcón-Pérez, JM and Barrio, R and Macarulla, T and Mato, JM and Martinez-Chantar, ML and Cordon-Cardo, C and Aransay, AM and Marks, K and Baselga, J and Tabernero, J and Nuciforo, P and Manning, BD and Marjon, K and Carracedo, A}, title = {Corrigendum: mTORC1-dependent AMD1 regulation sustains polyamine metabolism in prostate cancer.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {554}, pmid = {29342137}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature22964.}, } @article {pmid29342136, year = {2018}, author = {Tzoneva, G and Dieck, CL and Oshima, K and Ambesi-Impiombato, A and Sánchez-Martín, M and Madubata, CJ and Khiabanian, H and Yu, J and Waanders, E and Iacobucci, I and Sulis, ML and Kato, M and Koh, K and Paganin, M and Basso, G and Gastier-Foster, JM and Loh, ML and Kirschner-Schwabe, R and Mullighan, CG and Rabadan, R and Ferrando, AA}, title = {Clonal evolution mechanisms in NT5C2 mutant-relapsed acute lymphoblastic leukaemia.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {511-514}, pmid = {29342136}, issn = {1476-4687}, support = {R35 CA210065/CA/NCI NIH HHS/United States ; R01 CA185486/CA/NCI NIH HHS/United States ; U54 CA209997/CA/NCI NIH HHS/United States ; U24 CA114766/CA/NCI NIH HHS/United States ; T32 CA009503/CA/NCI NIH HHS/United States ; R01 CA216981/CA/NCI NIH HHS/United States ; R01 CA200651/CA/NCI NIH HHS/United States ; U54 CA193313/CA/NCI NIH HHS/United States ; P30 CA013696/CA/NCI NIH HHS/United States ; P30 CA016058/CA/NCI NIH HHS/United States ; U10 CA098543/CA/NCI NIH HHS/United States ; T32 GM008224/GM/NIGMS NIH HHS/United States ; F31 CA210607/CA/NCI NIH HHS/United States ; }, mesh = {5'-Nucleotidase/*genetics/*metabolism ; Animals ; Cell Proliferation ; *Clonal Evolution ; Disease Models, Animal ; Drug Resistance, Neoplasm/*genetics ; Female ; Gain of Function Mutation/genetics ; Guanosine/biosynthesis ; HEK293 Cells ; Humans ; IMP Dehydrogenase/antagonists & inhibitors/metabolism ; Male ; Mercaptopurine/pharmacology/therapeutic use ; Mice ; Mutation/*genetics ; Precursor Cell Lymphoblastic Leukemia-Lymphoma/*drug therapy/*genetics/metabolism/pathology ; Purines/metabolism ; Receptor, Notch1/metabolism ; Recurrence ; Xenograft Model Antitumor Assays ; }, abstract = {Relapsed acute lymphoblastic leukaemia (ALL) is associated with resistance to chemotherapy and poor prognosis. Gain-of-function mutations in the 5'-nucleotidase, cytosolic II (NT5C2) gene induce resistance to 6-mercaptopurine and are selectively present in relapsed ALL. Yet, the mechanisms involved in NT5C2 mutation-driven clonal evolution during the initiation of leukaemia, disease progression and relapse remain unknown. Here we use a conditional-and-inducible leukaemia model to demonstrate that expression of NT5C2(R367Q), a highly prevalent relapsed-ALL NT5C2 mutation, induces resistance to chemotherapy with 6-mercaptopurine at the cost of impaired leukaemia cell growth and leukaemia-initiating cell activity. The loss-of-fitness phenotype of NT5C2+/R367Q mutant cells is associated with excess export of purines to the extracellular space and depletion of the intracellular purine-nucleotide pool. Consequently, blocking guanosine synthesis by inhibition of inosine-5'-monophosphate dehydrogenase (IMPDH) induced increased cytotoxicity against NT5C2-mutant leukaemia lymphoblasts. These results identify the fitness cost of NT5C2 mutation and resistance to chemotherapy as key evolutionary drivers that shape clonal evolution in relapsed ALL and support a role for IMPDH inhibition in the treatment of ALL.}, } @article {pmid29342135, year = {2018}, author = {Lee, S and Choi, J and Mohanty, J and Sousa, LP and Tome, F and Pardon, E and Steyaert, J and Lemmon, MA and Lax, I and Schlessinger, J}, title = {Structures of β-klotho reveal a 'zip code'-like mechanism for endocrine FGF signalling.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {501-505}, pmid = {29342135}, issn = {1476-4687}, support = {1S10OD018007/NH/NIH HHS/United States ; }, mesh = {Binding Sites ; Crystallography, X-Ray ; Extracellular Space/metabolism ; Fibroblast Growth Factors/*chemistry/*metabolism ; Glycoside Hydrolases/chemistry/metabolism ; HEK293 Cells ; Humans ; Ligands ; Membrane Proteins/*chemistry/*metabolism ; Models, Molecular ; Protein Binding ; Protein Domains ; Receptors, Fibroblast Growth Factor/metabolism ; *Signal Transduction ; Substrate Specificity ; }, abstract = {Canonical fibroblast growth factors (FGFs) activate FGF receptors (FGFRs) through paracrine or autocrine mechanisms in a process that requires cooperation with heparan sulfate proteoglycans, which function as co-receptors for FGFR activation. By contrast, endocrine FGFs (FGF19, FGF21 and FGF23) are circulating hormones that regulate critical metabolic processes in a variety of tissues. FGF19 regulates bile acid synthesis and lipogenesis, whereas FGF21 stimulates insulin sensitivity, energy expenditure and weight loss. Endocrine FGFs signal through FGFRs in a manner that requires klothos, which are cell-surface proteins that possess tandem glycosidase domains. Here we describe the crystal structures of free and ligand-bound β-klotho extracellular regions that reveal the molecular mechanism that underlies the specificity of FGF21 towards β-klotho and demonstrate how the FGFR is activated in a klotho-dependent manner. β-Klotho serves as a primary 'zip code'-like receptor that acts as a targeting signal for FGF21, and FGFR functions as a catalytic subunit that mediates intracellular signalling. Our structures also show how the sugar-cutting enzyme glycosidase has evolved to become a specific receptor for hormones that regulate metabolic processes, including the lowering of blood sugar levels. Finally, we describe an agonistic variant of FGF21 with enhanced biological activity and present structural insights into the potential development of therapeutic agents for diseases linked to endocrine FGFs.}, } @article {pmid29342134, year = {2018}, author = {Bakhoum, SF and Ngo, B and Laughney, AM and Cavallo, JA and Murphy, CJ and Ly, P and Shah, P and Sriram, RK and Watkins, TBK and Taunk, NK and Duran, M and Pauli, C and Shaw, C and Chadalavada, K and Rajasekhar, VK and Genovese, G and Venkatesan, S and Birkbak, NJ and McGranahan, N and Lundquist, M and LaPlant, Q and Healey, JH and Elemento, O and Chung, CH and Lee, NY and Imielenski, M and Nanjangud, G and Pe'er, D and Cleveland, DW and Powell, SN and Lammerding, J and Swanton, C and Cantley, LC}, title = {Chromosomal instability drives metastasis through a cytosolic DNA response.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {467-472}, pmid = {29342134}, issn = {1476-4687}, support = {G0701935//Medical Research Council/United Kingdom ; K99 CA218871/CA/NCI NIH HHS/United States ; U54 CA210184/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R35 CA197588/CA/NCI NIH HHS/United States ; R35 GM122476/GM/NIGMS NIH HHS/United States ; R01 HL082792/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Brain Neoplasms/genetics/pathology/secondary ; Breast Neoplasms/genetics/pathology/secondary ; Carcinoma, Squamous Cell/genetics/pathology ; Cell Line ; *Chromosomal Instability/genetics ; Chromosome Segregation ; Cytosol/enzymology/*metabolism ; DNA, Neoplasm/*metabolism ; Female ; Head and Neck Neoplasms/genetics/pathology ; Humans ; Inflammation/genetics/metabolism ; Membrane Proteins/metabolism ; Mesoderm/metabolism ; Mice ; Micronuclei, Chromosome-Defective ; NF-kappa B/metabolism ; Neoplasm Metastasis/*genetics ; Nucleotidyltransferases/metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling. Genetic suppression of chromosomal instability markedly delays metastasis even in highly aneuploid tumour models, whereas continuous chromosome segregation errors promote cellular invasion and metastasis in a STING-dependent manner. By subverting lethal epithelial responses to cytosolic DNA, chromosomally unstable tumour cells co-opt chronic activation of innate immune pathways to spread to distant organs.}, } @article {pmid29342133, year = {2018}, author = {Bahr, C and von Paleske, L and Uslu, VV and Remeseiro, S and Takayama, N and Ng, SW and Murison, A and Langenfeld, K and Petretich, M and Scognamiglio, R and Zeisberger, P and Benk, AS and Amit, I and Zandstra, PW and Lupien, M and Dick, JE and Trumpp, A and Spitz, F}, title = {A Myc enhancer cluster regulates normal and leukaemic haematopoietic stem cell hierarchies.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {515-520}, pmid = {29342133}, issn = {1476-4687}, mesh = {Animals ; B-Lymphocytes/cytology ; Cell Differentiation ; Cell Lineage/genetics ; Chromatin/genetics/metabolism ; Down-Regulation ; Enhancer Elements, Genetic/*genetics ; Female ; Gene Deletion ; *Gene Expression Regulation ; Genes, myc/*genetics ; Hematopoietic Stem Cells/*cytology/*metabolism/pathology ; Humans ; Leukemia/*genetics/*pathology ; Leukemia, Myeloid, Acute/genetics/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Multigene Family/*genetics ; Multipotent Stem Cells/cytology ; Myeloid Cells/cytology ; Neoplastic Stem Cells/metabolism/pathology ; Prognosis ; Sequence Deletion ; Survival Analysis ; Transcription Factors/metabolism ; }, abstract = {The transcription factor Myc is essential for the regulation of haematopoietic stem cells and progenitors and has a critical function in haematopoietic malignancies. Here we show that an evolutionarily conserved region located 1.7 megabases downstream of the Myc gene that has previously been labelled as a 'super-enhancer' is essential for the regulation of Myc expression levels in both normal haematopoietic and leukaemic stem cell hierarchies in mice and humans. Deletion of this region in mice leads to a complete loss of Myc expression in haematopoietic stem cells and progenitors. This caused an accumulation of differentiation-arrested multipotent progenitors and loss of myeloid and B cells, mimicking the phenotype caused by Mx1-Cre-mediated conditional deletion of the Myc gene in haematopoietic stem cells. This super-enhancer comprises multiple enhancer modules with selective activity that recruits a compendium of transcription factors, including GFI1b, RUNX1 and MYB. Analysis of mice carrying deletions of individual enhancer modules suggests that specific Myc expression levels throughout most of the haematopoietic hierarchy are controlled by the combinatorial and additive activity of individual enhancer modules, which collectively function as a 'blood enhancer cluster' (BENC). We show that BENC is also essential for the maintenance of MLL-AF9-driven leukaemia in mice. Furthermore, a BENC module, which controls Myc expression in mouse haematopoietic stem cells and progenitors, shows increased chromatin accessibility in human acute myeloid leukaemia stem cells compared to blasts. This difference correlates with MYC expression and patient outcome. We propose that clusters of enhancers, such as BENC, form highly combinatorial systems that allow precise control of gene expression across normal cellular hierarchies and which also can be hijacked in malignancies.}, } @article {pmid29342132, year = {2018}, author = {Burlingame, Q and Coburn, C and Che, X and Panda, A and Qu, Y and Forrest, SR}, title = {Centimetre-scale electron diffusion in photoactive organic heterostructures.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {77-80}, doi = {10.1038/nature25148}, pmid = {29342132}, issn = {1476-4687}, abstract = {The unique properties of organic semiconductors, such as flexibility and lightness, are increasingly important for information displays, lighting and energy generation. But organics suffer from both static and dynamic disorder, and this can lead to variable-range carrier hopping, which results in notoriously poor electrical properties, with low electron and hole mobilities and correspondingly short charge-diffusion lengths of less than a micrometre. Here we demonstrate a photoactive (light-responsive) organic heterostructure comprising a thin fullerene channel sandwiched between an electron-blocking layer and a blended donor:C70 fullerene heterojunction that generates charges by dissociating excitons. Centimetre-scale diffusion of electrons is observed in the fullerene channel, and this can be fitted with a simple electron diffusion model. Our experiments enable the direct measurement of charge diffusivity in organic semiconductors, which is as high as 0.83 ± 0.07 square centimetres per second in a C60 channel at room temperature. The high diffusivity of the fullerene combined with the extraordinarily long charge-recombination time yields diffusion lengths of more than 3.5 centimetres, orders of magnitude larger than expected for an organic system.}, } @article {pmid29341896, year = {2018}, author = {Egbert, JR and Yee, SP and Jaffe, LA}, title = {Luteinizing hormone signaling phosphorylates and activates the cyclic GMP phosphodiesterase PDE5 in mouse ovarian follicles, contributing an additional component to the hormonally induced decrease in cyclic GMP that reinitiates meiosis.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {6-14}, pmid = {29341896}, issn = {1095-564X}, support = {R37 HD014939/HD/NICHD NIH HHS/United States ; }, mesh = {Amino Acid Substitution ; Animals ; Cyclic Nucleotide Phosphodiesterases, Type 5/genetics/*metabolism ; Female ; Luteinizing Hormone/genetics/*metabolism ; Meiosis/*physiology ; Mice ; Mice, Transgenic ; Mutation, Missense ; Ovarian Follicle/cytology/*metabolism ; Phosphorylation/genetics ; Rats ; Second Messenger Systems/*physiology ; }, abstract = {Prior to birth, oocytes within mammalian ovarian follicles initiate meiosis, but then arrest in prophase until puberty, when with each reproductive cycle, one or more follicles are stimulated by luteinizing hormone (LH) to resume meiosis in preparation for fertilization. Within preovulatory follicles, granulosa cells produce high levels of cGMP, which diffuses into the oocyte to maintain meiotic arrest. LH signaling restarts meiosis by rapidly lowering the levels of cGMP in the follicle and oocyte. Part of this decrease is mediated by the dephosphorylation and inactivation the NPR2 guanylyl cyclase in response to LH, but the mechanism for the remainder of the cGMP decrease is unknown. At least one cGMP phosphodiesterase, PDE5, is activated by LH signaling, which would contribute to lowering cGMP. PDE5 exhibits increased cGMP-hydrolytic activity when phosphorylated on serine 92, and we recently demonstrated that LH signaling phosphorylates PDE5 on this serine and increases its activity in rat follicles. To test the extent to which this mechanism contributes to the cGMP decrease that restarts meiosis, we generated a mouse line in which serine 92 was mutated to alanine (Pde5-S92A), such that it cannot be phosphorylated. Here we show that PDE5 phosphorylation is required for the LH-induced increase in cGMP-hydrolytic activity, but that this increase has only a modest effect on the LH-induced cGMP decrease in mouse follicles, and does not affect the timing of meiotic resumption. Though we show that the activation of PDE5 is among the mechanisms contributing to the cGMP decrease, these results suggest that another cGMP phosphodiesterase is also activated by LH signaling.}, } @article {pmid29341390, year = {2018}, author = {Pennell, TM and Holman, L and Morrow, EH and Field, J}, title = {Building a new research framework for social evolution: intralocus caste antagonism.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1251-1268}, pmid = {29341390}, issn = {1469-185X}, support = {695744//European Research Council/International ; }, abstract = {The breeding and non-breeding 'castes' of eusocial insects provide a striking example of role-specific selection, where each caste maximises fitness through different morphological, behavioural and physiological trait values. Typically, queens are long-lived egg-layers, while workers are short-lived, largely sterile foragers. Remarkably, the two castes are nevertheless produced by the same genome. The existence of inter-caste genetic correlations is a neglected consequence of this shared genome, potentially hindering the evolution of caste dimorphism: alleles that increase the productivity of queens may decrease the productivity of workers and vice versa, such that each caste is prevented from reaching optimal trait values. A likely consequence of this 'intralocus caste antagonism' should be the maintenance of genetic variation for fitness and maladaptation within castes (termed 'caste load'), analogous to the result of intralocus sexual antagonism. The aim of this review is to create a research framework for understanding caste antagonism, drawing in part upon conceptual similarities with sexual antagonism. By reviewing both the social insect and sexual antagonism literature, we highlight the current empirical evidence for caste antagonism, discuss social systems of interest, how antagonism might be resolved, and challenges for future research. We also introduce the idea that sexual and caste antagonism could interact, creating a three-way antagonism over gene expression. This includes unpacking the implications of haplodiploidy for the outcome of this complex interaction.}, } @article {pmid29340700, year = {2018}, author = {Caspermeyer, J}, title = {Finding Their Inner Bird: Using Modern Genomics to Turn Alligator Scales into Birdlike Feathers.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {523-524}, doi = {10.1093/molbev/msx330}, pmid = {29340700}, issn = {1537-1719}, mesh = {*Alligators and Crocodiles ; Animals ; Biological Evolution ; Birds ; *Feathers ; Genomics ; }, } @article {pmid29340696, year = {2018}, author = {Caspermeyer, J}, title = {From Southeast Asia to the Sewers: Study Determines New Geographic Origins of Brown Rats.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msx331}, pmid = {29340696}, issn = {1537-1719}, } @article {pmid29340608, year = {2018}, author = {Caspermeyer, J}, title = {Could Increasing Cancer Incidence Be Tied to Human Adaptation of Living in Extreme Environments?.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, doi = {10.1093/molbev/msx329}, pmid = {29340608}, issn = {1537-1719}, } @article {pmid29340582, year = {2018}, author = {Pawluk, RJ and Uren Webster, TM and Cable, J and Garcia de Leaniz, C and Consuegra, S}, title = {Immune-Related Transcriptional Responses to Parasitic Infection in a Naturally Inbred Fish: Roles of Genotype and Individual Variation.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {319-327}, pmid = {29340582}, issn = {1759-6653}, mesh = {Adaptive Immunity ; Animals ; Cyprinodontiformes/*genetics/immunology/*parasitology ; Fish Diseases/*genetics/immunology/*parasitology ; Gene Expression Profiling ; Gene Expression Regulation ; Gene Ontology ; Genotype ; Host-Parasite Interactions ; *Inbreeding ; *Transcriptome ; }, abstract = {Parasites are strong drivers of evolutionary change and the genetic variation of both host and parasite populations can co-evolve as a function of parasite virulence and host resistance. The role of transcriptome variation in specific interactions between host and parasite genotypes has been less studied and can be confounded by differences in genetic variation. We employed two naturally inbred lines of a self-fertilizing fish to estimate the role of host genotype in the transcriptome response to parasite infection using RNA-seq. In addition, we targeted several differentially expressed immune-related genes to further investigate the relative role of individual variation in the immune response using RT-qPCR, taking advantage of the genomic uniformity of the self-fertilizing lines. We found significant differences in gene expression between lines in response to infection both in the transcriptome and in individual gene RT-qPCR analyses. Individual RT-qPCR analyses of gene expression identified significant variance differences between lines for six genes but only for three genes between infected and control fish. Our results indicate that although the genetic background plays an important role in the transcriptome response to parasites, it cannot fully explain individual differences within genetically homogeneous lines, which can be important for determining the response to parasites.}, } @article {pmid29340581, year = {2018}, author = {Hoffmann, FG and Vandewege, MW and Storz, JF and Opazo, JC}, title = {Gene Turnover and Diversification of the α- and β-Globin Gene Families in Sauropsid Vertebrates.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {344-358}, pmid = {29340581}, issn = {1759-6653}, support = {R01 HL087216/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; Gene Duplication ; Genome ; *Multigene Family ; *Phylogeny ; Reptiles/genetics ; Vertebrates/genetics ; alpha-Globins/*genetics ; beta-Globins/*genetics ; }, abstract = {The genes that encode the α- and β-chain subunits of vertebrate hemoglobin have served as a model system for elucidating general principles of gene family evolution, but little is known about patterns of evolution in amniotes other than mammals and birds. Here, we report a comparative genomic analysis of the α- and β-globin gene clusters in sauropsids (archosaurs and nonavian reptiles). The objectives were to characterize changes in the size and membership composition of the α- and β-globin gene families within and among the major sauropsid lineages, to reconstruct the evolutionary history of the sauropsid α- and β-globin genes, to resolve orthologous relationships, and to reconstruct evolutionary changes in the developmental regulation of gene expression. Our comparisons revealed contrasting patterns of evolution in the unlinked α- and β-globin gene clusters. In the α-globin gene cluster, which has remained in the ancestral chromosomal location, evolutionary changes in gene content are attributable to the differential retention of paralogous gene copies that were present in the common ancestor of tetrapods. In the β-globin gene cluster, which was translocated to a new chromosomal location, evolutionary changes in gene content are attributable to differential gene gains (via lineage-specific duplication events) and gene losses (via lineage-specific deletions and inactivations). Consequently, all major groups of amniotes possess unique repertoires of embryonic and postnatally expressed β-type globin genes that diversified independently in each lineage. These independently derived β-type globins descend from a pair of tandemly linked paralogs in the most recent common ancestor of sauropsids.}, } @article {pmid29340007, year = {2018}, author = {Steffani-Vallejo, JL and Brunck, ME and Acosta-Cruz, EY and Montiel, R and Barona-Gómez, F}, title = {Genomic insights into Mycobacterium simiae human colonization.}, journal = {Standards in genomic sciences}, volume = {13}, number = {}, pages = {1}, pmid = {29340007}, issn = {1944-3277}, abstract = {Mycobacterium simiae (Karassova V, Weissfeiler J, Kraszanay E, Acta Microbiol Acad Sci Hung 12:275-82, 1965) is a slow-growing nontuberculous Mycobacterium species found in environmental niches, and recently evidenced as an opportunistic Human pathogen. We report here the genome of a clinical isolate of M. simiae (MsiGto) obtained from a patient in Guanajuato, Mexico. With a size of 6,684,413 bp, the genomic sequence of strain MsiGto is the largest of the three M. simiae genomes reported to date. Gene prediction revealed 6409 CDSs in total, including 6354 protein-coding genes and 52 RNA genes. Comparative genomic analysis identified shared features between strain MsiGto and the other two reported M. simiae genomes, as well as unique genes. Our data reveals that M. simiae MsiGto harbors virulence-related genes, such as arcD, ESAT-6, and those belonging to the antigen 85 complex and mce clusters, which may explain its successful transition to the human host. We expect the genome information of strain MsiGto will provide a better understanding of infective mechanisms and virulence of this emergent pathogen.}, } @article {pmid29339667, year = {2018}, author = {Hannema, SE and de Rijke, YB}, title = {Improving Laboratory Assessment in Disorders of Sex Development through a Multidisciplinary Network.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {135-139}, pmid = {29339667}, issn = {1661-5433}, mesh = {Clinical Laboratory Techniques/*methods ; Disorders of Sex Development/blood/*diagnosis ; Hormones/blood ; Humans ; *Interdisciplinary Studies ; }, abstract = {The aim of the European Reference Network for Rare Endocrine Disorders (Endo-ERN) is to ensure equal access to high-quality care for all those affected by a rare endocrine condition across Europe, such as a disorder/difference of sex development (DSD), both for children and adults. Although differences in resources, health care systems, and health insurances between the European countries are challenging and require political action, a European laboratory network within Endo-ERN could improve the diagnostic process in individuals with DSD, building on the work done by previous European collaborations such as the COST action DSDnet. In close collaboration, clinicians and laboratory specialists must make every effort to standardize diagnostic protocols, achieve necessary harmonization of various laboratory tests, e.g., the hCG stimulation test, and implement an external quality control system. This should ideally result in comparable quality across the network centers allowing the sharing of reference values. This would not only improve patient care but also greatly facilitate research.}, } @article {pmid29339547, year = {2018}, author = {Goldman, DP and Chen, C and Zissimopoulos, J and Rowe, JW and , }, title = {Opinion: Measuring how countries adapt to societal aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {435-437}, pmid = {29339547}, issn = {1091-6490}, mesh = {Aged ; Aged, 80 and over ; Aging/*psychology ; Attitude ; Cross-Cultural Comparison ; Female ; Humans ; Male ; Quality of Life ; }, } @article {pmid29339525, year = {2018}, author = {Fischer, C and Luttge, A}, title = {Pulsating dissolution of crystalline matter.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {897-902}, pmid = {29339525}, issn = {1091-6490}, abstract = {Fluid-solid reactions result in material flux from or to the solid surface. The prediction of the flux, its variations, and changes with time are of interest to a wide array of disciplines, ranging from the material and earth sciences to pharmaceutical sciences. Reaction rate maps that are derived from sequences of topography maps illustrate the spatial distribution of reaction rates across the crystal surface. Here, we present highly spatially resolved rate maps that reveal the existence of rhythmic pulses of the material flux from the crystal surface. This observation leads to a change in our understanding of the way crystalline matter dissolves. Rhythmic fluctuations of the reactive surface site density and potentially concomitant oscillations in the fluid saturation imply spatial and temporal variability in surface reaction rates. Knowledge of such variability could aid attempts to upscale microscopic rates and predict reactive transport through changing porous media.}, } @article {pmid29339524, year = {2018}, author = {Casella, A and Kartik, N and Sanchez, L and Turban, S}, title = {Communication in context: Interpreting promises in an experiment on competition and trust.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {933-938}, pmid = {29339524}, issn = {1091-6490}, mesh = {*Communication ; Competitive Behavior ; Games, Experimental ; Humans ; Models, Psychological ; *Trust ; }, abstract = {How much do people lie, and how much do people trust communication when lying is possible? An important step toward answering these questions is understanding how communication is interpreted. This paper establishes in a canonical experiment that competition can alter the shared communication code: the commonly understood meaning of messages. We study a sender-receiver game in which the sender dictates how to share $10 with the receiver, if the receiver participates. The receiver has an outside option and decides whether to participate after receiving a nonbinding offer from the sender. Competition for play between senders leads to higher offers but has no effect on actual transfers, expected transfers, or receivers' willingness to play. The higher offers signal that sharing will be equitable without the expectation that they should be followed literally: Under competition "6 is the new 5."}, } @article {pmid29339523, year = {2018}, author = {Burke, CR and Lupták, A}, title = {DNA synthesis from diphosphate substrates by DNA polymerases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {980-985}, pmid = {29339523}, issn = {1091-6490}, support = {R01 GM094929/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; DNA Replication ; DNA, Bacterial/*biosynthesis/genetics ; DNA-Directed DNA Polymerase/genetics/*metabolism ; Deoxyribonucleotides/metabolism ; Kinetics ; Substrate Specificity ; Taq Polymerase/genetics/metabolism ; }, abstract = {The activity of DNA polymerase underlies numerous biotechnologies, cell division, and therapeutics, yet the enzyme remains incompletely understood. We demonstrate that both thermostable and mesophilic DNA polymerases readily utilize deoxyribonucleoside diphosphates (dNDPs) for DNA synthesis and inorganic phosphate for the reverse reaction, that is, phosphorolysis of DNA. For Taq DNA polymerase, the KMs of the dNDP and phosphate substrates are ∼20 and 200 times higher than for dNTP and pyrophosphate, respectively. DNA synthesis from dNDPs is about 17 times slower than from dNTPs, and DNA phosphorolysis about 200 times less efficient than pyrophosphorolysis. Such parameters allow DNA replication without requiring coupled metabolism to sequester the phosphate products, which consequently do not pose a threat to genome stability. This mechanism contrasts with DNA synthesis from dNTPs, which yield high-energy pyrophosphates that have to be hydrolyzed to phosphates to prevent the reverse reaction. Because the last common ancestor was likely a thermophile, dNDPs are plausible substrates for genome replication on early Earth and may represent metabolic intermediates later replaced by the higher-energy triphosphates.}, } @article {pmid29339522, year = {2018}, author = {Le, K and Steagall, WK and Stylianou, M and Pacheco-Rodriguez, G and Darling, TN and Vaughan, M and Moss, J}, title = {Effect of beta-agonists on LAM progression and treatment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E944-E953}, pmid = {29339522}, issn = {1091-6490}, mesh = {Adrenergic beta-Agonists/*pharmacology ; Adult ; Aged ; Bronchodilator Agents/pharmacology ; Catalytic Domain ; Cell Proliferation/drug effects ; Cyclic AMP/metabolism ; Cyclic AMP-Dependent Protein Kinases/metabolism ; Disease Progression ; Female ; Fibroblasts/cytology/metabolism ; Humans ; Isoproterenol/pharmacology ; Lymphangioleiomyomatosis/*drug therapy/*metabolism ; Middle Aged ; Multivariate Analysis ; Phosphorylation ; Respiratory Function Tests ; Retrospective Studies ; Signal Transduction/drug effects ; Sirolimus/pharmacology ; Skin/metabolism ; TOR Serine-Threonine Kinases/metabolism ; Tuberous Sclerosis Complex 1 Protein ; Tuberous Sclerosis Complex 2 Protein ; Tumor Suppressor Proteins/*genetics/metabolism ; }, abstract = {Lymphangioleiomyomatosis (LAM), a rare disease of women, is associated with cystic lung destruction resulting from the proliferation of abnormal smooth muscle-like LAM cells with mutations in the tuberous sclerosis complex (TSC) genes TSC1 and/or TSC2 The mutant genes and encoded proteins are responsible for activation of the mechanistic target of rapamycin (mTOR), which is inhibited by sirolimus (rapamycin), a drug used to treat LAM. Patients who have LAM may also be treated with bronchodilators for asthma-like symptoms due to LAM. We observed stabilization of forced expiratory volume in 1 s over time in patients receiving sirolimus and long-acting beta-agonists with short-acting rescue inhalers compared with patients receiving only sirolimus. Because beta-agonists increase cAMP and PKA activity, we investigated effects of PKA activation on the mTOR pathway. Human skin TSC2+/- fibroblasts or LAM lung cells incubated short-term with isoproterenol (beta-agonist) showed a sirolimus-independent increase in phosphorylation of S6, a downstream effector of the mTOR pathway, and increased cell growth. Cells incubated long-term with isoproterenol, which may lead to beta-adrenergic receptor desensitization, did not show increased S6 phosphorylation. Inhibition of PKA blocked the isoproterenol effect on S6 phosphorylation. Thus, activation of PKA by beta-agonists increased phospho-S6 independent of mTOR, an effect abrogated by beta-agonist-driven receptor desensitization. In agreement, retrospective clinical data from patients with LAM suggested that a combination of bronchodilators in conjunction with sirolimus may be preferable to sirolimus alone for stabilization of pulmonary function.}, } @article {pmid29339521, year = {2018}, author = {Phillips, KP and Cable, J and Mohammed, RS and Herdegen-Radwan, M and Raubic, J and Przesmycka, KJ and van Oosterhout, C and Radwan, J}, title = {Immunogenetic novelty confers a selective advantage in host-pathogen coevolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {1552-1557}, pmid = {29339521}, issn = {1091-6490}, mesh = {Animals ; Ectoparasitic Infestations/immunology/parasitology/*veterinary ; *Evolution, Molecular ; Fish Diseases/immunology/parasitology ; Host-Parasite Interactions/*genetics ; *Immunogenetics ; Major Histocompatibility Complex/genetics/*immunology ; Poecilia/*genetics/parasitology ; *Selection, Genetic ; }, abstract = {The major histocompatibility complex (MHC) is crucial to the adaptive immune response of vertebrates and is among the most polymorphic gene families known. Its high diversity is usually attributed to selection imposed by fast-evolving pathogens. Pathogens are thought to evolve to escape recognition by common immune alleles, and, hence, novel MHC alleles, introduced through mutation, recombination, or gene flow, are predicted to give hosts superior resistance. Although this theoretical prediction underpins host-pathogen "Red Queen" coevolution, it has not been demonstrated in the context of natural MHC diversity. Here, we experimentally tested whether novel MHC variants (both alleles and functional "supertypes") increased resistance of guppies (Poecilia reticulata) to a common ectoparasite (Gyrodactylus turnbulli). We used exposure-controlled infection trials with wild-sourced parasites, and Gyrodactylus-naïve host fish that were F2 descendants of crossed wild populations. Hosts carrying MHC variants (alleles or supertypes) that were new to a given parasite population experienced a 35-37% reduction in infection intensity, but the number of MHC variants carried by an individual, analogous to heterozygosity in single-locus systems, was not a significant predictor. Our results provide direct evidence of novel MHC variant advantage, confirming a fundamental mechanism underpinning the exceptional polymorphism of this gene family and highlighting the role of immunogenetic novelty in host-pathogen coevolution.}, } @article {pmid29339520, year = {2018}, author = {Choi, JH and Jeong, YM and Kim, S and Lee, B and Ariyasiri, K and Kim, HT and Jung, SH and Hwang, KS and Choi, TI and Park, CO and Huh, WK and Carl, M and Rosenfeld, JA and Raskin, S and Ma, A and Gecz, J and Kim, HG and Kim, JS and Shin, HC and Park, DS and Gerlai, R and Jamieson, BB and Kim, JS and Iremonger, KJ and Lee, SH and Shin, HS and Kim, CH}, title = {Targeted knockout of a chemokine-like gene increases anxiety and fear responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1041-E1050}, pmid = {29339520}, issn = {1091-6490}, mesh = {Animals ; Anxiety/*genetics ; Anxiety Disorders ; Autism Spectrum Disorder/*genetics ; Behavior, Animal ; Chemokines/*genetics ; Conditioning (Psychology)/physiology ; Disease Models, Animal ; *Fear ; Female ; Gene Deletion ; Genetic Variation ; Green Fluorescent Proteins/metabolism ; Homozygote ; Humans ; Male ; Mice ; Mice, Knockout ; *Mutation ; RNA, Messenger/metabolism ; Social Behavior ; Zebrafish ; }, abstract = {Emotional responses, such as fear and anxiety, are fundamentally important behavioral phenomena with strong fitness components in most animal species. Anxiety-related disorders continue to represent a major unmet medical need in our society, mostly because we still do not fully understand the mechanisms of these diseases. Animal models may speed up discovery of these mechanisms. The zebrafish is a highly promising model organism in this field. Here, we report the identification of a chemokine-like gene family, samdori (sam), and present functional characterization of one of its members, sam2 We show exclusive mRNA expression of sam2 in the CNS, predominantly in the dorsal habenula, telencephalon, and hypothalamus. We found knockout (KO) zebrafish to exhibit altered anxiety-related responses in the tank, scototaxis and shoaling assays, and increased crh mRNA expression in their hypothalamus compared with wild-type fish. To investigate generalizability of our findings to mammals, we developed a Sam2 KO mouse and compared it to wild-type littermates. Consistent with zebrafish findings, homozygous KO mice exhibited signs of elevated anxiety. We also found bath application of purified SAM2 protein to increase inhibitory postsynaptic transmission onto CRH neurons of the paraventricular nucleus. Finally, we identified a human homolog of SAM2, and were able to refine a candidate gene region encompassing SAM2, among 21 annotated genes, which is associated with intellectual disability and autism spectrum disorder in the 12q14.1 deletion syndrome. Taken together, these results suggest a crucial and evolutionarily conserved role of sam2 in regulating mechanisms associated with anxiety.}, } @article {pmid29339519, year = {2018}, author = {Lucas, BA and Lavi, E and Shiue, L and Cho, H and Katzman, S and Miyoshi, K and Siomi, MC and Carmel, L and Ares, M and Maquat, LE}, title = {Evidence for convergent evolution of SINE-directed Staufen-mediated mRNA decay.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {968-973}, pmid = {29339519}, issn = {1091-6490}, support = {R01 GM040478/GM/NIGMS NIH HHS/United States ; }, mesh = {3' Untranslated Regions ; AT Rich Sequence ; Animals ; *Evolution, Molecular ; Humans ; Mice ; Protein-Serine-Threonine Kinases/genetics/metabolism ; RNA Stability/*genetics ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/*metabolism ; *Short Interspersed Nucleotide Elements ; }, abstract = {Primate-specific Alu short interspersed elements (SINEs) as well as rodent-specific B and ID (B/ID) SINEs can promote Staufen-mediated decay (SMD) when present in mRNA 3'-untranslated regions (3'-UTRs). The transposable nature of SINEs, their presence in long noncoding RNAs, their interactions with Staufen, and their rapid divergence in different evolutionary lineages suggest they could have generated substantial modification of posttranscriptional gene-control networks during mammalian evolution. Some of the variation in SMD regulation produced by SINE insertion might have had a similar regulatory effect in separate mammalian lineages, leading to parallel evolution of the Staufen network by independent expansion of lineage-specific SINEs. To explore this possibility, we searched for orthologous gene pairs, each carrying a species-specific 3'-UTR SINE and each regulated by SMD, by measuring changes in mRNA abundance after individual depletion of two SMD factors, Staufen1 (STAU1) and UPF1, in both human and mouse myoblasts. We identified and confirmed orthologous gene pairs with 3'-UTR SINEs that independently function in SMD control of myoblast metabolism. Expanding to other species, we demonstrated that SINE-directed SMD likely emerged in both primate and rodent lineages >20-25 million years ago. Our work reveals a mechanism for the convergent evolution of posttranscriptional gene regulatory networks in mammals by species-specific SINE transposition and SMD.}, } @article {pmid29339518, year = {2018}, author = {Rezaei Araghi, R and Bird, GH and Ryan, JA and Jenson, JM and Godes, M and Pritz, JR and Grant, RA and Letai, A and Walensky, LD and Keating, AE}, title = {Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E886-E895}, pmid = {29339518}, issn = {1091-6490}, support = {R01 GM110048/GM/NIGMS NIH HHS/United States ; R21 CA209358/CA/NCI NIH HHS/United States ; R35 CA197583/CA/NCI NIH HHS/United States ; R50 CA211399/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; Cell Line ; Cell Survival ; Circular Dichroism ; Crystallography, X-Ray ; Cytoplasm/metabolism ; Drug Design ; Humans ; Hydrophobic and Hydrophilic Interactions ; Inhibitory Concentration 50 ; Mice ; Mutation ; Myeloid Cell Leukemia Sequence 1 Protein/*metabolism ; Neoplasms/*metabolism ; Peptides/*chemistry ; Protein Binding ; Protein Interaction Mapping ; Spectrometry, Fluorescence ; }, abstract = {Bcl-2 family proteins regulate apoptosis, and aberrant interactions of overexpressed antiapoptotic family members such as Mcl-1 promote cell transformation, cancer survival, and resistance to chemotherapy. Discovering potent and selective Mcl-1 inhibitors that can relieve apoptotic blockades is thus a high priority for cancer research. An attractive strategy for disabling Mcl-1 involves using designer peptides to competitively engage its binding groove, mimicking the structural mechanism of action of native sensitizer BH3-only proteins. We transformed Mcl-1-binding peptides into α-helical, cell-penetrating constructs that are selectively cytotoxic to Mcl-1-dependent cancer cells. Critical to the design of effective inhibitors was our introduction of an all-hydrocarbon cross-link or "staple" that stabilizes α-helical structure, increases target binding affinity, and independently confers binding specificity for Mcl-1 over related Bcl-2 family paralogs. Two crystal structures of complexes at 1.4 Å and 1.9 Å resolution demonstrate how the hydrophobic staple induces an unanticipated structural rearrangement in Mcl-1 upon binding. Systematic sampling of staple location and iterative optimization of peptide sequence in accordance with established design principles provided peptides that target intracellular Mcl-1. This work provides proof of concept for the development of potent, selective, and cell-permeable stapled peptides for therapeutic targeting of Mcl-1 in cancer, applying a design and validation workflow applicable to a host of challenging biomedical targets.}, } @article {pmid29339517, year = {2018}, author = {Azasi, Y and Lindergard, G and Ghumra, A and Mu, J and Miller, LH and Rowe, JA}, title = {Infected erythrocytes expressing DC13 PfEMP1 differ from recombinant proteins in EPCR-binding function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1063-1068}, pmid = {29339517}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 084226//Wellcome Trust/United Kingdom ; 095831//Wellcome Trust/United Kingdom ; }, mesh = {Brain/metabolism/pathology ; Cell Adhesion ; Cell Line ; Endothelial Protein C Receptor/metabolism ; Epitopes/chemistry ; Erythrocytes/*parasitology ; Humans ; Malaria, Cerebral/*parasitology ; Malaria, Falciparum/*parasitology ; Microcirculation ; Molecular Weight ; Oligopeptides/*metabolism ; Plasmodium falciparum/*metabolism ; Protein Binding ; Protozoan Proteins/*metabolism ; RNA, Small Interfering/metabolism ; Receptors, Cell Surface/metabolism ; Recombinant Proteins/metabolism ; }, abstract = {Recent advances have identified a new paradigm for cerebral malaria pathogenesis in which endothelial protein C receptor (EPCR) is a major host receptor for sequestration of Plasmodium falciparum-infected erythrocytes (IEs) in the brain and other vital organs. The parasite adhesins that bind EPCR are members of the IE variant surface antigen family Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) containing specific adhesion domains called domain cassette (DC) 8 and DC13. The binding interaction site between PfEMP1 and EPCR has been mapped by biophysical and crystallography studies using recombinant proteins. However, studies examining the interaction of native PfEMP1 on the IE surface with EPCR are few. We aimed to study binding to EPCR by IEs expressing DC8 and DC13 PfEMP1 variants whose recombinant proteins have been used in key prior functional and structural studies. IE binding to EPCR immobilized on plastic and on human brain endothelial cells was examined in static and flow adhesion assays. Unexpectedly, we found that IEs expressing the DC13 PfEMP1 variant HB3var03 or IT4var07 did not bind to EPCR on plastic and the binding of these variants to brain endothelial cells was not dependent on EPCR. IEs expressing the DC8 variant IT4var19 did bind to EPCR, but this interaction was inhibited if normal human serum or plasma was present, raising the possibility that IE-EPCR interaction may be prevented by plasma components under physiological conditions. These data highlight a discrepancy in EPCR-binding activity between PfEMP1 recombinant proteins and IEs, and indicate the critical need for further research to understand the pathophysiological significance of the PfEMP1-EPCR interaction.}, } @article {pmid29339516, year = {2018}, author = {Smith, BM and Traboulsi, H and Austin, JHM and Manichaikul, A and Hoffman, EA and Bleecker, ER and Cardoso, WV and Cooper, C and Couper, DJ and Dashnaw, SM and Guo, J and Han, MK and Hansel, NN and Hughes, EW and Jacobs, DR and Kanner, RE and Kaufman, JD and Kleerup, E and Lin, CL and Liu, K and Lo Cascio, CM and Martinez, FJ and Nguyen, JN and Prince, MR and Rennard, S and Rich, SS and Simon, L and Sun, Y and Watson, KE and Woodruff, PG and Baglole, CJ and Barr, RG and , }, title = {Human airway branch variation and chronic obstructive pulmonary disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E974-E981}, pmid = {29339516}, issn = {1091-6490}, support = {HHSN268200900019C/HL/NHLBI NIH HHS/United States ; N01HC95160/HL/NHLBI NIH HHS/United States ; N01HC95161/HL/NHLBI NIH HHS/United States ; R01 HL112986/HL/NHLBI NIH HHS/United States ; P30 ES005605/ES/NIEHS NIH HHS/United States ; N01HC95168/HL/NHLBI NIH HHS/United States ; N01HC95169/HL/NHLBI NIH HHS/United States ; R01 HL077612/HL/NHLBI NIH HHS/United States ; RC1 HL100543/HL/NHLBI NIH HHS/United States ; K24 HL137013/HL/NHLBI NIH HHS/United States ; N01HC95164/HL/NHLBI NIH HHS/United States ; N01HC95162/HL/NHLBI NIH HHS/United States ; R01 HL093081/HL/NHLBI NIH HHS/United States ; HHSN268200900015C/HL/NHLBI NIH HHS/United States ; N01HC95165/HL/NHLBI NIH HHS/United States ; HHSN268200900016C/HL/NHLBI NIH HHS/United States ; U01 HL114494/HL/NHLBI NIH HHS/United States ; N01HC95167/HL/NHLBI NIH HHS/United States ; HHSN268200900018C/HL/NHLBI NIH HHS/United States ; R01 HL121270/HL/NHLBI NIH HHS/United States ; N01HC95163/HL/NHLBI NIH HHS/United States ; U01 HL137880/HL/NHLBI NIH HHS/United States ; N01HC95159/HL/NHLBI NIH HHS/United States ; P30 DK054759/DK/NIDDK NIH HHS/United States ; R01 HL130506/HL/NHLBI NIH HHS/United States ; HHSN268200900017C/HL/NHLBI NIH HHS/United States ; HHSN268200900020C/HL/NHLBI NIH HHS/United States ; HHSN268200900013C/HL/NHLBI NIH HHS/United States ; N01HC95166/HL/NHLBI NIH HHS/United States ; HHSN268200900014C/HL/NHLBI NIH HHS/United States ; R35 HL135834/HL/NHLBI NIH HHS/United States ; P30 ES009089/ES/NIEHS NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Bronchi/anatomy & histology/*physiopathology ; Disease Susceptibility ; Female ; Fibroblast Growth Factor 10/*genetics ; Genotype ; Humans ; Image Processing, Computer-Assisted ; Lung/physiopathology ; Male ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide ; Prospective Studies ; Pulmonary Disease, Chronic Obstructive/genetics/*physiopathology ; Pulmonary Emphysema/physiopathology ; Respiration ; Smoking ; Tomography, X-Ray Computed ; Trachea/anatomy & histology/*physiopathology ; }, abstract = {Susceptibility to chronic obstructive pulmonary disease (COPD) beyond cigarette smoking is incompletely understood, although several genetic variants associated with COPD are known to regulate airway branch development. We demonstrate that in vivo central airway branch variants are present in 26.5% of the general population, are unchanged over 10 y, and exhibit strong familial aggregation. The most common airway branch variant is associated with COPD in two cohorts (n = 5,054), with greater central airway bifurcation density, and with emphysema throughout the lung. The second most common airway branch variant is associated with COPD among smokers, with narrower airway lumens in all lobes, and with genetic polymorphisms within the FGF10 gene. We conclude that central airway branch variation, readily detected by computed tomography, is a biomarker of widely altered lung structure with a genetic basis and represents a COPD susceptibility factor.}, } @article {pmid29339515, year = {2018}, author = {Menachery, VD and Schäfer, A and Burnum-Johnson, KE and Mitchell, HD and Eisfeld, AJ and Walters, KB and Nicora, CD and Purvine, SO and Casey, CP and Monroe, ME and Weitz, KK and Stratton, KG and Webb-Robertson, BM and Gralinski, LE and Metz, TO and Smith, RD and Waters, KM and Sims, AC and Kawaoka, Y and Baric, RS}, title = {MERS-CoV and H5N1 influenza virus antagonize antigen presentation by altering the epigenetic landscape.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1012-E1021}, pmid = {29339515}, issn = {1091-6490}, support = {P41 GM103493/GM/NIGMS NIH HHS/United States ; R00 AG049092/AG/NIA NIH HHS/United States ; K99 AG049092/AG/NIA NIH HHS/United States ; U19 AI106772/AI/NIAID NIH HHS/United States ; U19 AI100625/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Antigen Presentation ; Antigenic Variation ; Cell Line ; Cercopithecus aethiops ; DNA Methylation ; Dogs ; Down-Regulation ; *Epigenesis, Genetic ; Histones/chemistry ; Humans ; Influenza A Virus, H5N1 Subtype/*pathogenicity ; Madin Darby Canine Kidney Cells ; Major Histocompatibility Complex ; Middle East Respiratory Syndrome Coronavirus/*pathogenicity ; Mutation ; Open Reading Frames ; Proteomics ; Vero Cells ; }, abstract = {Convergent evolution dictates that diverse groups of viruses will target both similar and distinct host pathways to manipulate the immune response and improve infection. In this study, we sought to leverage this uneven viral antagonism to identify critical host factors that govern disease outcome. Utilizing a systems-based approach, we examined differential regulation of IFN-γ-dependent genes following infection with robust respiratory viruses including influenza viruses [A/influenza/Vietnam/1203/2004 (H5N1-VN1203) and A/influenza/California/04/2009 (H1N1-CA04)] and coronaviruses [severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome CoV (MERS-CoV)]. Categorizing by function, we observed down-regulation of gene expression associated with antigen presentation following both H5N1-VN1203 and MERS-CoV infection. Further examination revealed global down-regulation of antigen-presentation gene expression, which was confirmed by proteomics for both H5N1-VN1203 and MERS-CoV infection. Importantly, epigenetic analysis suggested that DNA methylation, rather than histone modification, plays a crucial role in MERS-CoV-mediated antagonism of antigen-presentation gene expression; in contrast, H5N1-VN1203 likely utilizes a combination of epigenetic mechanisms to target antigen presentation. Together, the results indicate a common mechanism utilized by H5N1-VN1203 and MERS-CoV to modulate antigen presentation and the host adaptive immune response.}, } @article {pmid29339514, year = {2018}, author = {Kenett, YN and Levy, O and Kenett, DY and Stanley, HE and Faust, M and Havlin, S}, title = {Flexibility of thought in high creative individuals represented by percolation analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {867-872}, pmid = {29339514}, issn = {1091-6490}, mesh = {Cognition ; *Creativity ; Humans ; Memory ; *Models, Psychological ; Semantic Web ; *Thinking ; }, abstract = {Flexibility of thought is theorized to play a critical role in the ability of high creative individuals to generate novel and innovative ideas. However, this has been examined only through indirect behavioral measures. Here we use network percolation analysis (removal of links in a network whose strength is below an increasing threshold) to computationally examine the robustness of the semantic memory networks of low and high creative individuals. Robustness of a network indicates its flexibility and thus can be used to quantify flexibility of thought as related to creativity. This is based on the assumption that the higher the robustness of the semantic network, the higher its flexibility. Our analysis reveals that the semantic network of high creative individuals is more robust to network percolation compared with the network of low creative individuals and that this higher robustness is related to differences in the structure of the networks. Specifically, we find that this higher robustness is related to stronger links connecting between different components of similar semantic words in the network, which may also help to facilitate spread of activation over their network. Thus, we directly and quantitatively examine the relation between flexibility of thought and creative ability. Our findings support the associative theory of creativity, which posits that high creative ability is related to a flexible structure of semantic memory. Finally, this approach may have further implications, by enabling a quantitative examination of flexibility of thought, in both healthy and clinical populations.}, } @article {pmid29339513, year = {2018}, author = {Bio, BJ and Webb, TW and Graziano, MSA}, title = {Projecting one's own spatial bias onto others during a theory-of-mind task.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1684-E1689}, pmid = {29339513}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Attention ; Bias ; Cognition ; Female ; Humans ; Middle Aged ; *Space Perception ; Young Adult ; }, abstract = {Many people show a left-right bias in visual processing. We measured spatial bias in neurotypical participants using a variant of the line bisection task. In the same participants, we measured performance in a social cognition task. This theory-of-mind task measured whether each participant had a processing-speed bias toward the right of, or left of, a cartoon agent about which the participant was thinking. Crucially, the cartoon was rotated such that what was left and right with respect to the cartoon was up and down with respect to the participant. Thus, a person's own left-right bias could not align directly onto left and right with respect to the cartoon head. Performance on the two tasks was significantly correlated. People who had a natural bias toward processing their own left side of space were quicker to process how the cartoon might think about objects to the left side of its face, and likewise for a rightward bias. One possible interpretation of these results is that the act of processing one's own personal space shares some of the same underlying mechanisms as the social cognitive act of reconstructing someone else's processing of their space.}, } @article {pmid29339512, year = {2018}, author = {Feng, G and Ingvalson, EM and Grieco-Calub, TM and Roberts, MY and Ryan, ME and Birmingham, P and Burrowes, D and Young, NM and Wong, PCM}, title = {Neural preservation underlies speech improvement from auditory deprivation in young cochlear implant recipients.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1022-E1031}, pmid = {29339512}, issn = {1091-6490}, mesh = {Brain Mapping ; Child ; Child, Preschool ; *Cochlear Implantation ; *Cochlear Implants ; Deafness/rehabilitation ; Female ; Hearing ; Humans ; Language Development ; Machine Learning ; Magnetic Resonance Imaging ; Male ; Models, Neurological ; Multivariate Analysis ; Nerve Net ; Neuroanatomy ; Neurons/*physiology ; Speech/*physiology ; Speech Perception ; Speech Therapy/methods ; }, abstract = {Although cochlear implantation enables some children to attain age-appropriate speech and language development, communicative delays persist in others, and outcomes are quite variable and difficult to predict, even for children implanted early in life. To understand the neurobiological basis of this variability, we used presurgical neural morphological data obtained from MRI of individual pediatric cochlear implant (CI) candidates implanted younger than 3.5 years to predict variability of their speech-perception improvement after surgery. We first compared neuroanatomical density and spatial pattern similarity of CI candidates to that of age-matched children with normal hearing, which allowed us to detail neuroanatomical networks that were either affected or unaffected by auditory deprivation. This information enables us to build machine-learning models to predict the individual children's speech development following CI. We found that regions of the brain that were unaffected by auditory deprivation, in particular the auditory association and cognitive brain regions, produced the highest accuracy, specificity, and sensitivity in patient classification and the most precise prediction results. These findings suggest that brain areas unaffected by auditory deprivation are critical to developing closer to typical speech outcomes. Moreover, the findings suggest that determination of the type of neural reorganization caused by auditory deprivation before implantation is valuable for predicting post-CI language outcomes for young children.}, } @article {pmid29339511, year = {2018}, author = {Preston, SH and Vierboom, YC and Stokes, A}, title = {The role of obesity in exceptionally slow US mortality improvement.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {957-961}, pmid = {29339511}, issn = {1091-6490}, support = {R01 AG040212/AG/NIA NIH HHS/United States ; R03 SH000037/SH/NCHS CDC HHS/United States ; T32 HD007242/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Aged ; Aged, 80 and over ; Body Mass Index ; Female ; Humans ; Life Expectancy/trends ; Male ; Middle Aged ; Mortality/*trends ; Nutrition Surveys ; Obesity/epidemiology/*mortality ; Prevalence ; United States/epidemiology ; }, abstract = {Recent studies have described a reduction in the rate of improvement in American mortality. The pace of improvement is also slow by international standards. This paper attempts to identify the extent to which rising body mass index (BMI) is responsible for reductions in the rate of mortality improvement in the United States. The data for this study were obtained from subsequent cohorts of the National Health and Nutrition Examination Survey (NHANES III, 1988-1994; NHANES continuous, 1999-2010) and from the NHANES linked mortality files, which include follow-up into death records through December 2011. The role of BMI was estimated using Cox models comparing mortality trends in the presence and absence of adjustment for maximum lifetime BMI (Max BMI). Introducing Max BMI into a Cox model controlling for age and sex raised the annual rate of mortality decline by 0.54% (95% confidence interval 0.45-0.64%). Results were robust to the inclusion of other variables in the model, to differences in how Max BMI was measured, and to how trends were evaluated. The effect of rising Max BMI is large relative to international mortality trends and to alternative mortality futures simulated by the Social Security Administration. The increase in Max BMI over the period 1988-2011 is estimated to have reduced life expectancy at age 40 by 0.9 years in 2011 (95% confidence interval 0.7-1.1 years) and accounted for 186,000 excess deaths that year. Rising levels of BMI have prevented the United States from enjoying the full benefits of factors working to improve mortality.}, } @article {pmid29339510, year = {2018}, author = {Points, LJ and Taylor, JW and Grizou, J and Donkers, K and Cronin, L}, title = {Artificial intelligence exploration of unstable protocells leads to predictable properties and discovery of collective behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {885-890}, pmid = {29339510}, issn = {1091-6490}, support = {BB/M011267/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Algorithms ; *Artificial Cells ; *Artificial Intelligence ; Automation ; Machine Learning ; Models, Biological ; Models, Chemical ; Oils ; *Origin of Life ; Phase Transition ; Robotics ; Water ; }, abstract = {Protocell models are used to investigate how cells might have first assembled on Earth. Some, like oil-in-water droplets, can be seemingly simple models, while able to exhibit complex and unpredictable behaviors. How such simple oil-in-water systems can come together to yield complex and life-like behaviors remains a key question. Herein, we illustrate how the combination of automated experimentation and image processing, physicochemical analysis, and machine learning allows significant advances to be made in understanding the driving forces behind oil-in-water droplet behaviors. Utilizing >7,000 experiments collected using an autonomous robotic platform, we illustrate how smart automation cannot only help with exploration, optimization, and discovery of new behaviors, but can also be core to developing fundamental understanding of such systems. Using this process, we were able to relate droplet formulation to behavior via predicted physical properties, and to identify and predict more occurrences of a rare collective droplet behavior, droplet swarming. Proton NMR spectroscopic and qualitative pH methods enabled us to better understand oil dissolution, chemical change, phase transitions, and droplet and aqueous phase flows, illustrating the utility of the combination of smart-automation and traditional analytical chemistry techniques. We further extended our study for the simultaneous exploration of both the oil and aqueous phases using a robotic platform. Overall, this work shows that the combination of chemistry, robotics, and artificial intelligence enables discovery, prediction, and mechanistic understanding in ways that no one approach could achieve alone.}, } @article {pmid29339509, year = {2018}, author = {Curry, EJ and Ke, K and Chorsi, MT and Wrobel, KS and Miller, AN and Patel, A and Kim, I and Feng, J and Yue, L and Wu, Q and Kuo, CL and Lo, KW and Laurencin, CT and Ilies, H and Purohit, PK and Nguyen, TD}, title = {Biodegradable Piezoelectric Force Sensor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {909-914}, pmid = {29339509}, issn = {1091-6490}, support = {R01 HL078960/HL/NHLBI NIH HHS/United States ; R21 EB024787/EB/NIBIB NIH HHS/United States ; }, mesh = {*Absorbable Implants ; Animals ; Biomechanical Phenomena ; Electricity ; Humans ; Mice ; Monitoring, Physiologic/*instrumentation ; Polyesters ; *Pressure ; }, abstract = {Measuring vital physiological pressures is important for monitoring health status, preventing the buildup of dangerous internal forces in impaired organs, and enabling novel approaches of using mechanical stimulation for tissue regeneration. Pressure sensors are often required to be implanted and directly integrated with native soft biological systems. Therefore, the devices should be flexible and at the same time biodegradable to avoid invasive removal surgery that can damage directly interfaced tissues. Despite recent achievements in degradable electronic devices, there is still a tremendous need to develop a force sensor which only relies on safe medical materials and requires no complex fabrication process to provide accurate information on important biophysiological forces. Here, we present a strategy for material processing, electromechanical analysis, device fabrication, and assessment of a piezoelectric Poly-l-lactide (PLLA) polymer to create a biodegradable, biocompatible piezoelectric force sensor, which only employs medical materials used commonly in Food and Drug Administration-approved implants, for the monitoring of biological forces. We show the sensor can precisely measure pressures in a wide range of 0-18 kPa and sustain a reliable performance for a period of 4 d in an aqueous environment. We also demonstrate this PLLA piezoelectric sensor can be implanted inside the abdominal cavity of a mouse to monitor the pressure of diaphragmatic contraction. This piezoelectric sensor offers an appealing alternative to present biodegradable electronic devices for the monitoring of intraorgan pressures. The sensor can be integrated with tissues and organs, forming self-sensing bionic systems to enable many exciting applications in regenerative medicine, drug delivery, and medical devices.}, } @article {pmid29339508, year = {2018}, author = {Dean, KR and Krauer, F and Walløe, L and Lingjærde, OC and Bramanti, B and Stenseth, NC and Schmid, BV}, title = {Human ectoparasites and the spread of plague in Europe during the Second Pandemic.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1304-1309}, pmid = {29339508}, issn = {1091-6490}, mesh = {Animals ; Bayes Theorem ; Disease Vectors ; Ectoparasitic Infestations ; Epidemiologic Methods ; Europe/epidemiology ; Humans ; Markov Chains ; *Models, Statistical ; Pandemics ; *Pediculus/microbiology ; Plague/*epidemiology/mortality/parasitology/*transmission ; Rodentia ; *Siphonaptera/microbiology ; Yersinia pestis/pathogenicity ; }, abstract = {Plague, caused by the bacterium Yersinia pestis, can spread through human populations by multiple transmission pathways. Today, most human plague cases are bubonic, caused by spillover of infected fleas from rodent epizootics, or pneumonic, caused by inhalation of infectious droplets. However, little is known about the historical spread of plague in Europe during the Second Pandemic (14-19th centuries), including the Black Death, which led to high mortality and recurrent epidemics for hundreds of years. Several studies have suggested that human ectoparasite vectors, such as human fleas (Pulex irritans) or body lice (Pediculus humanus humanus), caused the rapidly spreading epidemics. Here, we describe a compartmental model for plague transmission by a human ectoparasite vector. Using Bayesian inference, we found that this model fits mortality curves from nine outbreaks in Europe better than models for pneumonic or rodent transmission. Our results support that human ectoparasites were primary vectors for plague during the Second Pandemic, including the Black Death (1346-1353), ultimately challenging the assumption that plague in Europe was predominantly spread by rats.}, } @article {pmid29339507, year = {2018}, author = {Zhang, Y and Harris, CJ and Liu, Q and Liu, W and Ausin, I and Long, Y and Xiao, L and Feng, L and Chen, X and Xie, Y and Chen, X and Zhan, L and Feng, S and Li, JJ and Wang, H and Zhai, J and Jacobsen, SE}, title = {Large-scale comparative epigenomics reveals hierarchical regulation of non-CG methylation in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1069-E1074}, pmid = {29339507}, issn = {1091-6490}, support = {R01 GM060398/GM/NIGMS NIH HHS/United States ; R37 GM060398/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/*genetics ; Cluster Analysis ; Computational Biology ; CpG Islands ; *DNA Methylation ; Epigenesis, Genetic ; *Epigenomics ; *Gene Expression Regulation, Plant ; Gene Library ; Genome, Plant ; Heterochromatin/chemistry ; High-Throughput Nucleotide Sequencing ; Plants, Genetically Modified ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Software ; }, abstract = {Genome-wide characterization by next-generation sequencing has greatly improved our understanding of the landscape of epigenetic modifications. Since 2008, whole-genome bisulfite sequencing (WGBS) has become the gold standard for DNA methylation analysis, and a tremendous amount of WGBS data has been generated by the research community. However, the systematic comparison of DNA methylation profiles to identify regulatory mechanisms has yet to be fully explored. Here we reprocessed the raw data of over 500 publicly available Arabidopsis WGBS libraries from various mutant backgrounds, tissue types, and stress treatments and also filtered them based on sequencing depth and efficiency of bisulfite conversion. This enabled us to identify high-confidence differentially methylated regions (hcDMRs) by comparing each test library to over 50 high-quality wild-type controls. We developed statistical and quantitative measurements to analyze the overlapping of DMRs and to cluster libraries based on their effect on DNA methylation. In addition to confirming existing relationships, we revealed unanticipated connections between well-known genes. For instance, MET1 and CMT3 were found to be required for the maintenance of asymmetric CHH methylation at nonoverlapping regions of CMT2 targeted heterochromatin. Our comparative methylome approach has established a framework for extracting biological insights via large-scale comparison of methylomes and can also be adopted for other genomics datasets.}, } @article {pmid29339506, year = {2018}, author = {Cao, X and Hong, Y and Zhu, L and Hu, Y and Cronan, JE}, title = {Development and retention of a primordial moonlighting pathway of protein modification in the absence of selection presents a puzzle.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {647-655}, pmid = {29339506}, issn = {1091-6490}, mesh = {Acyltransferases/metabolism ; Amino Acid Oxidoreductases/metabolism ; Amino Acid Sequence ; Bacillus subtilis/metabolism ; Bacterial Proteins/genetics/*metabolism ; Biological Evolution ; Carrier Proteins/metabolism ; Escherichia coli/metabolism ; Evolution, Molecular ; Gram-Negative Bacteria/genetics/metabolism ; Gram-Positive Bacteria/genetics/metabolism ; Lipoylation ; Multienzyme Complexes/metabolism ; Peptide Synthases/metabolism ; Protein Processing, Post-Translational ; Thioctic Acid/*biosynthesis/genetics ; Transferases/genetics/metabolism ; }, abstract = {Lipoic acid is synthesized by a remarkably atypical pathway in which the cofactor is assembled on its cognate proteins. An octanoyl moiety diverted from fatty acid synthesis is covalently attached to the acceptor protein, and sulfur insertion at carbons 6 and 8 of the octanoyl moiety form the lipoyl cofactor. Covalent attachment of this cofactor is required for function of several central metabolism enzymes, including the glycine cleavage H protein (GcvH). In Bacillus subtilis, GcvH is the sole substrate for lipoate assembly. Hence lipoic acid-requiring 2-oxoacid dehydrogenase (OADH) proteins acquire the cofactor only by transfer from lipoylated GcvH. Lipoyl transfer has been argued to be the primordial pathway of OADH lipoylation. The Escherichia coli pathway where lipoate is directly assembled on both its GcvH and OADH proteins, is proposed to have arisen later. Because roughly 3 billion years separate the divergence of these bacteria, it is surprising that E. coli GcvH functionally substitutes for the B. subtilis protein in lipoyl transfer. Known and putative GcvHs from other bacteria and eukaryotes also substitute for B. subtilis GcvH in OADH modification. Because glycine cleavage is the primary GcvH role in ancestral bacteria that lack OADH enzymes, lipoyl transfer is a "moonlighting" function: that is, development of a new function while retaining the original function. This moonlighting has been conserved in the absence of selection by some, but not all, GcvH proteins. Moreover, Aquifex aeolicus encodes five putative GcvHs, two of which have the moonlighting function, whereas others function only in glycine cleavage.}, } @article {pmid29339505, year = {2018}, author = {Barbado, C and Córdoba-Cañero, D and Ariza, RR and Roldán-Arjona, T}, title = {Nonenzymatic release of N7-methylguanine channels repair of abasic sites into an AP endonuclease-independent pathway in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E916-E924}, pmid = {29339505}, issn = {1091-6490}, mesh = {Arabidopsis/*enzymology/*genetics ; Arabidopsis Proteins/*genetics ; Binding Sites ; Catalysis ; Cell-Free System ; DNA Damage ; *DNA Methylation ; DNA Repair ; DNA-(Apurinic or Apyrimidinic Site) Lyase/*genetics ; Endonucleases/*genetics ; Gene Expression Regulation, Plant ; Guanine/analogs & derivatives/chemistry ; Mutation ; Protein Domains ; }, abstract = {Abasic (apurinic/apyrimidinic, AP) sites in DNA arise from spontaneous base loss or by enzymatic removal during base excision repair. It is commonly accepted that both classes of AP site have analogous biochemical properties and are equivalent substrates for AP endonucleases and AP lyases, although the relative roles of these two types of enzymes are not well understood. We provide here genetic and biochemical evidence that, in Arabidopsis, AP sites generated by spontaneous loss of N7-methylguanine (N7-meG) are exclusively repaired through an AP endonuclease-independent pathway initiated by FPG, a bifunctional DNA glycosylase with AP lyase activity. Abasic site incision catalyzed by FPG generates a single-nucleotide gap with a 3'-phosphate terminus that is processed by the DNA 3'-phosphatase ZDP before repair is completed. We further show that the major AP endonuclease in Arabidopsis (ARP) incises AP sites generated by enzymatic N7-meG excision but, unexpectedly, not those resulting from spontaneous N7-meG loss. These findings, which reveal previously undetected differences between products of enzymatic and nonenzymatic base release, may shed light on the evolution and biological roles of AP endonucleases and AP lyases.}, } @article {pmid29339504, year = {2018}, author = {Esmail, H and Lai, RP and Lesosky, M and Wilkinson, KA and Graham, CM and Horswell, S and Coussens, AK and Barry, CE and O'Garra, A and Wilkinson, RJ}, title = {Complement pathway gene activation and rising circulating immune complexes characterize early disease in HIV-associated tuberculosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E964-E973}, pmid = {29339504}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; MC_U117588499//Medical Research Council/United Kingdom ; R01 HL106804/HL/NHLBI NIH HHS/United States ; U19 AI111276/AI/NIAID NIH HHS/United States ; 090170//Wellcome Trust/United Kingdom ; 203135//Wellcome Trust/United Kingdom ; 104803//Wellcome Trust/United Kingdom ; 37822//Wellcome Trust/United Kingdom ; FC00110218//Cancer Research UK/United Kingdom ; FC00110218//Medical Research Council/United Kingdom ; FC00110218//Wellcome Trust/United Kingdom ; }, mesh = {Antibodies/blood ; Antigen-Antibody Complex/*blood ; Cluster Analysis ; Coinfection ; Comorbidity ; Complement System Proteins/*genetics ; Disease Progression ; Fluorodeoxyglucose F18 ; HIV Infections/complications/*immunology ; Humans ; Interferons/immunology ; Oligonucleotide Array Sequence Analysis ; Positron Emission Tomography Computed Tomography ; Signal Transduction ; Transcription, Genetic ; Transcriptional Activation ; Transcriptome ; Tuberculosis/complications/*immunology ; }, abstract = {The transition between latent and active tuberculosis (TB) occurs before symptom onset. Better understanding of the early events in subclinical disease will facilitate the development of diagnostics and interventions that improve TB control. This is particularly relevant in the context of HIV-1 coinfection where progression of TB is more likely. In a recent study using [18F]-fluoro-2-deoxy-d-glucose positron emission/computed tomography (FDG-PET/CT) on 35 asymptomatic, HIV-1-infected adults, we identified 10 participants with radiographic evidence of subclinical disease, significantly more likely to progress than the 25 participants without. To gain insight into the biological events in early disease, we performed blood-based whole genome transcriptomic analysis on these participants and 15 active patients with TB. We found transcripts representing the classical complement pathway and Fcγ receptor 1 overabundant from subclinical stages of disease. Levels of circulating immune (antibody/antigen) complexes also increased in subclinical disease and were highly correlated with C1q transcript abundance. To validate our findings, we analyzed transcriptomic data from a publicly available dataset where samples were available in the 2 y before TB disease presentation. Transcripts representing the classical complement pathway and Fcγ receptor 1 were also differentially expressed in the 12 mo before disease presentation. Our results indicate that levels of antibody/antigen complexes increase early in disease, associated with increased gene expression of C1q and Fcγ receptors that bind them. Understanding the role this plays in disease progression may facilitate development of interventions that prevent this, leading to a more favorable outcome and may also be important to diagnostic development.}, } @article {pmid29339503, year = {2018}, author = {Vantourout, P and Laing, A and Woodward, MJ and Zlatareva, I and Apolonia, L and Jones, AW and Snijders, AP and Malim, MH and Hayday, AC}, title = {Heteromeric interactions regulate butyrophilin (BTN) and BTN-like molecules governing γδ T cell biology.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1039-1044}, pmid = {29339503}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 106292/Z/14/Z//Wellcome Trust/United Kingdom ; 100156/Z/12/Z//Wellcome Trust/United Kingdom ; 106223/Z/14/Z//Wellcome Trust/United Kingdom ; FC001093//Cancer Research UK/United Kingdom ; FC001093//Medical Research Council/United Kingdom ; FC001093//Department of Health/United Kingdom ; }, mesh = {Amino Acid Motifs ; Animals ; Antigens, CD/chemistry/immunology/metabolism ; Butyrophilins/chemistry/*immunology/*metabolism ; Endoplasmic Reticulum/immunology/metabolism ; HEK293 Cells ; Humans ; Lymphocyte Activation ; Mice ; Protein Multimerization ; Receptors, Antigen, T-Cell, gamma-delta/*metabolism ; T-Lymphocyte Subsets/*immunology/*metabolism ; }, abstract = {The long-held view that gamma delta (γδ) T cells in mice and humans are fundamentally dissimilar, as are γδ cells in blood and peripheral tissues, has been challenged by emerging evidence of the cells' regulation by butyrophilin (BTN) and butyrophilin-like (BTNL) molecules. Thus, murine Btnl1 and the related gene, Skint1, mediate T cell receptor (TCR)-dependent selection of murine intraepithelial γδ T cell repertoires in gut and skin, respectively; BTNL3 and BTNL8 are TCR-dependent regulators of human gut γδ cells; and BTN3A1 is essential for TCR-dependent activation of human peripheral blood Vγ9Vδ2+ T cells. However, some observations concerning BTN/Btnl molecules continue to question the extent of mechanistic conservation. In particular, murine and human gut γδ cell regulation depends on pairings of Btnl1 and Btnl6 and BTNL3 and BTNL8, respectively, whereas blood γδ cells are reported to be regulated by BTN3A1 independent of other BTNs. Addressing this paradox, we show that BTN3A2 regulates the subcellular localization of BTN3A1, including functionally important associations with the endoplasmic reticulum (ER), and is specifically required for optimal BTN3A1-mediated activation of Vγ9Vδ2+ T cells. Evidence that BTNL3/BTNL8 and Btnl1/Btnl6 likewise associate with the ER reinforces the prospect of broadly conserved mechanisms underpinning the selection and activation of γδ cells in mice and humans, and in blood and extralymphoid sites.}, } @article {pmid29339502, year = {2018}, author = {Russo, C and Osterburg, C and Sirico, A and Antonini, D and Ambrosio, R and Würz, JM and Rinnenthal, J and Ferniani, M and Kehrloesser, S and Schäfer, B and Güntert, P and Sinha, S and Dötsch, V and Missero, C}, title = {Protein aggregation of the p63 transcription factor underlies severe skin fragility in AEC syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E906-E915}, pmid = {29339502}, issn = {1091-6490}, mesh = {Animals ; Cleft Lip/*genetics ; Cleft Palate/*genetics ; Ectoderm/metabolism ; Eye Abnormalities/*genetics ; Frameshift Mutation ; HEK293 Cells ; Heterozygote ; Humans ; Mice ; Mutation ; Mutation, Missense ; Phosphoproteins/*genetics ; Protein Binding ; Protein Denaturation ; Skin/*pathology ; Trans-Activators/*genetics ; Transcription Factors/*genetics/*metabolism ; Transcription, Genetic ; Tumor Suppressor Proteins/*genetics/*metabolism ; }, abstract = {The p63 gene encodes a master regulator of epidermal commitment, development, and differentiation. Heterozygous mutations in the C-terminal domain of the p63 gene can cause ankyloblepharon-ectodermal defects-cleft lip/palate (AEC) syndrome, a life-threatening disorder characterized by skin fragility and severe, long-lasting skin erosions. Despite deep knowledge of p63 functions, little is known about mechanisms underlying disease pathology and possible treatments. Here, we show that multiple AEC-associated p63 mutations, but not those causative of other diseases, lead to thermodynamic protein destabilization, misfolding, and aggregation, similar to the known p53 gain-of-function mutants found in cancer. AEC mutant proteins exhibit impaired DNA binding and transcriptional activity, leading to dominant negative effects due to coaggregation with wild-type p63 and p73. Importantly, p63 aggregation occurs also in a conditional knock-in mouse model for the disorder, in which the misfolded p63 mutant protein leads to severe epidermal defects. Variants of p63 that abolish aggregation of the mutant proteins are able to rescue p63's transcriptional function in reporter assays as well as in a human fibroblast-to-keratinocyte conversion assay. Our studies reveal that AEC syndrome is a protein aggregation disorder and opens avenues for therapeutic intervention.}, } @article {pmid29339501, year = {2018}, author = {}, title = {Correction to Supporting Information for Carlson et al., Effect of oil palm sustainability certification on deforestation and fire in Indonesia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E842-E843}, doi = {10.1073/pnas.1722311115}, pmid = {29339501}, issn = {1091-6490}, } @article {pmid29339500, year = {2018}, author = {An, Z and Liu, Y and Ou, Y and Li, J and Zhang, B and Sun, D and Sun, Y and Tang, W}, title = {Regulation of the stability of RGF1 receptor by the ubiquitin-specific proteases UBP12/UBP13 is critical for root meristem maintenance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1123-1128}, pmid = {29339500}, issn = {1091-6490}, mesh = {Arabidopsis/physiology ; Arabidopsis Proteins/*metabolism ; Cell Membrane/metabolism ; Endopeptidases/*metabolism ; Gene Expression Regulation, Plant ; Ligands ; Meristem/*physiology ; Peptide Hormones/metabolism ; Peptides/*metabolism ; Phenotype ; Phosphorylation ; Plant Roots/*physiology ; Plants, Genetically Modified/physiology ; Proteasome Endopeptidase Complex/*metabolism ; Protein Interaction Mapping ; Signal Transduction ; Ubiquitin-Specific Proteases/metabolism ; Ubiquitination ; }, abstract = {ROOT MERISTEM GROWTH FACTOR (RGF) 1 is an important peptide hormone that regulates root growth. Upon binding to its receptor, RGFR1, RGF1 regulates the expression of two transcription factors, PLETHORA 1 and 2 (PLT1/2), to influence root meristem development. Here, we show that the ubiquitin-specific proteases UBP12 and UBP13 are positive regulators of root meristem development and that UBP13 interacts directly with RGF1 receptor (RGFR1) and its close homolog RGFR2. The ubp12,13 double-mutant root is completely insensitive to exogenous applied RGF1. Consistent with this result, RGF1-induced ubiquitination and turnover of RGFR1 protein were accelerated in ubp12,13-mutant plants but were delayed in transgenic plants overexpressing UBP13 Genetic analysis showed that PLT2 or RGFR1 overexpression partially rescued the short-root phenotype and the reduced cortical root meristem cell number in ubp12,13 plants. Together, our results demonstrate that UBP12/13 are regulators of the RGF1-RGFR1-PLT1/2 signaling pathway and that UBP12/13 can counteract RGF1-induced RGFR1 ubiquitination, stabilize RGFR1, and maintain root cell sensitivity to RGF1.}, } @article {pmid29339499, year = {2018}, author = {Wan, J and Tokunaga, TK and Ashby, PD and Kim, Y and Voltolini, M and Gilbert, B and DePaolo, DJ}, title = {Supercritical CO2 uptake by nonswelling phyllosilicates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {873-878}, pmid = {29339499}, issn = {1091-6490}, abstract = {Interactions between supercritical (sc) CO2 and minerals are important when CO2 is injected into geologic formations for storage and as working fluids for enhanced oil recovery, hydraulic fracturing, and geothermal energy extraction. It has previously been shown that at the elevated pressures and temperatures of the deep subsurface, scCO2 alters smectites (typical swelling phyllosilicates). However, less is known about the effects of scCO2 on nonswelling phyllosilicates (illite and muscovite), despite the fact that the latter are the dominant clay minerals in deep subsurface shales and mudstones. Our studies conducted by using single crystals, combining reaction (incubation with scCO2), visualization [atomic force microscopy (AFM)], and quantifications (AFM, X-ray photoelectron spectroscopy, X-ray diffraction, and off-gassing measurements) revealed unexpectedly high CO2 uptake that far exceeded its macroscopic surface area. Results from different methods collectively suggest that CO2 partially entered the muscovite interlayers, although the pathways remain to be determined. We hypothesize that preferential dissolution at weaker surface defects and frayed edges allows CO2 to enter the interlayers under elevated pressure and temperature, rather than by diffusing solely from edges deeply into interlayers. This unexpected uptake of CO2, can increase CO2 storage capacity by up to ∼30% relative to the capacity associated with residual trapping in a 0.2-porosity sandstone reservoir containing up to 18 mass % of illite/muscovite. This excess CO2 uptake constitutes a previously unrecognized potential trapping mechanism.}, } @article {pmid29339498, year = {2018}, author = {Iacovazzo, D and Flanagan, SE and Walker, E and Quezado, R and de Sousa Barros, FA and Caswell, R and Johnson, MB and Wakeling, M and Brändle, M and Guo, M and Dang, MN and Gabrovska, P and Niederle, B and Christ, E and Jenni, S and Sipos, B and Nieser, M and Frilling, A and Dhatariya, K and Chanson, P and de Herder, WW and Konukiewitz, B and Klöppel, G and Stein, R and Korbonits, M and Ellard, S}, title = {MAFA missense mutation causes familial insulinomatosis and diabetes mellitus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1027-1032}, pmid = {29339498}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; F32 DK109577/DK/NIDDK NIH HHS/United States ; R01 DK090570/DK/NIDDK NIH HHS/United States ; //Department of Health/United Kingdom ; 105636/Z/14/Z//Wellcome Trust/United Kingdom ; 098395/Z/12/A//Wellcome Trust/United Kingdom ; }, mesh = {Diabetes Mellitus/*genetics/metabolism/pathology ; Female ; Genes, Dominant ; Humans ; Hyperinsulinism/*genetics/metabolism/pathology ; Insulinoma/*genetics/metabolism/pathology ; Maf Transcription Factors, Large/*genetics/metabolism ; Male ; Mutant Proteins/*genetics/metabolism ; *Mutation, Missense ; Neuroendocrine Tumors/*genetics/metabolism/pathology ; Pancreatic Neoplasms/*genetics/metabolism/pathology ; Pedigree ; Protein Stability ; Transcriptional Activation ; Whole Exome Sequencing ; }, abstract = {The β-cell-enriched MAFA transcription factor plays a central role in regulating glucose-stimulated insulin secretion while also demonstrating oncogenic transformation potential in vitro. No disease-causing MAFA variants have been previously described. We investigated a large pedigree with autosomal dominant inheritance of diabetes mellitus or insulinomatosis, an adult-onset condition of recurrent hyperinsulinemic hypoglycemia caused by multiple insulin-secreting neuroendocrine tumors of the pancreas. Using exome sequencing, we identified a missense MAFA mutation (p.Ser64Phe, c.191C>T) segregating with both phenotypes of insulinomatosis and diabetes. This mutation was also found in a second unrelated family with the same clinical phenotype, while no germline or somatic MAFA mutations were identified in nine patients with sporadic insulinomatosis. In the two families, insulinomatosis presented more frequently in females (eight females/two males) and diabetes more often in males (12 males/four females). Four patients from the index family, including two homozygotes, had a history of congenital cataract and/or glaucoma. The p.Ser64Phe mutation was found to impair phosphorylation within the transactivation domain of MAFA and profoundly increased MAFA protein stability under both high and low glucose concentrations in β-cell lines. In addition, the transactivation potential of p.Ser64Phe MAFA in β-cell lines was enhanced compared with wild-type MAFA. In summary, the p.Ser64Phe missense MAFA mutation leads to familial insulinomatosis or diabetes by impacting MAFA protein stability and transactivation ability. The human phenotypes associated with the p.Ser64Phe MAFA missense mutation reflect both the oncogenic capacity of MAFA and its key role in islet β-cell activity.}, } @article {pmid29339497, year = {2018}, author = {D'Asaro, EA and Shcherbina, AY and Klymak, JM and Molemaker, J and Novelli, G and Guigand, CM and Haza, AC and Haus, BK and Ryan, EH and Jacobs, GA and Huntley, HS and Laxague, NJM and Chen, S and Judt, F and McWilliams, JC and Barkan, R and Kirwan, AD and Poje, AC and Özgökmen, TM}, title = {Ocean convergence and the dispersion of flotsam.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1162-1167}, pmid = {29339497}, issn = {1091-6490}, abstract = {Floating oil, plastics, and marine organisms are continually redistributed by ocean surface currents. Prediction of their resulting distribution on the surface is a fundamental, long-standing, and practically important problem. The dominant paradigm is dispersion within the dynamical context of a nondivergent flow: objects initially close together will on average spread apart but the area of surface patches of material does not change. Although this paradigm is likely valid at mesoscales, larger than 100 km in horizontal scale, recent theoretical studies of submesoscales (less than ∼10 km) predict strong surface convergences and downwelling associated with horizontal density fronts and cyclonic vortices. Here we show that such structures can dramatically concentrate floating material. More than half of an array of ∼200 surface drifters covering ∼20 × 20 km2 converged into a 60 × 60 m region within a week, a factor of more than 105 decrease in area, before slowly dispersing. As predicted, the convergence occurred at density fronts and with cyclonic vorticity. A zipperlike structure may play an important role. Cyclonic vorticity and vertical velocity reached 0.001 s-1 and 0.01 ms-1, respectively, which is much larger than usually inferred. This suggests a paradigm in which nearby objects form submesoscale clusters, and these clusters then spread apart. Together, these effects set both the overall extent and the finescale texture of a patch of floating material. Material concentrated at submesoscale convergences can create unique communities of organisms, amplify impacts of toxic material, and create opportunities to more efficiently recover such material.}, } @article {pmid29339496, year = {2018}, author = {Ochiai, S and Jagot, F and Kyle, RL and Hyde, E and White, RF and Prout, M and Schmidt, AJ and Yamane, H and Lamiable, O and Le Gros, G and Ronchese, F}, title = {Thymic stromal lymphopoietin drives the development of IL-13+ Th2 cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1033-1038}, pmid = {29339496}, issn = {1091-6490}, mesh = {Adoptive Transfer ; Animals ; Cell Differentiation/immunology ; Cytokines/deficiency/genetics/*immunology ; Female ; Humans ; Interleukin-13/genetics/metabolism ; Interleukin-4/genetics/metabolism ; Male ; Mice ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Receptors, Interleukin-7/metabolism ; Th2 Cells/classification/cytology/*immunology ; }, abstract = {T helper 2 (Th2) cells are pivotal in the development of allergy. Allergen exposure primes IL-4+ Th2 cells in lymph node, but production of effector cytokines including IL-5 and IL-13 is thought to require additional signals from antigen and the environment. Here we report that a substantial proportion of naive CD4+ T cells in spleen and lymph node express receptors for the epithelium-derived inflammatory cytokine thymic stromal lymphopoietin (TSLP). Culture of naive CD4+ T cells in anti-(a)CD3, aCD28, and TSLP-supplemented Th2 conditions enabled the development of a unique population of IL-13-single positive (IL-13-SP) CD4+ T cells; TSLP and Th2 conditions were both required for their development. Sorting experiments revealed that IL-13-SP Th2 cells originated from IL-4-negative precursors and coexpressed transcripts for the Th2 cytokines IL-5 and IL-9. In vivo, high TSLP levels acted directly on CD4+ T cells to induce the development of IL-13-SP and IL-4+IL-13+ double-positive populations in lymph node. These cells were phenotypically similar to Th2 effector cells and were CXCR5lowPD1low and expressed low levels of Bcl6 and Il21 transcripts and high levels of Gata3, Il3, and Il5 Our findings suggest a role of TSLP in directly promoting Th2 cell effector function and support the notion of TSLP as a key driver of Th2 inflammation.}, } @article {pmid29339495, year = {2018}, author = {Jalili, R and Horecka, J and Swartz, JR and Davis, RW and Persson, HHJ}, title = {Streamlined circular proximity ligation assay provides high stringency and compatibility with low-affinity antibodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E925-E933}, pmid = {29339495}, issn = {1091-6490}, support = {F32 HG000205/HG/NHGRI NIH HHS/United States ; P01 HG000205/HG/NHGRI NIH HHS/United States ; }, mesh = {Antibodies/*chemistry ; Antibody Affinity ; Biomarkers/*chemistry ; Blood Proteins/*chemistry ; DNA, Single-Stranded/chemistry ; Dose-Response Relationship, Drug ; Humans ; Immunoassay ; Oligonucleotides ; Phosphorylation ; Polymerase Chain Reaction ; Protein Binding ; Protein Interaction Mapping/*methods ; Proteomics ; Reproducibility of Results ; }, abstract = {Proximity ligation assay (PLA) is a powerful tool for quantitative detection of protein biomarkers in biological fluids and tissues. Here, we present the circular proximity ligation assay (c-PLA), a highly specific protein detection method that outperforms traditional PLA in stringency, ease of use, and compatibility with low-affinity reagents. In c-PLA, two proximity probes bind to an analyte, providing a scaffolding that positions two free oligonucleotides such that they can be ligated into a circular DNA molecule. This assay format stabilizes antigen proximity probe complexes and enhances stringency by reducing the probability of random background ligation events. Circle formation also increases selectivity, since the uncircularized DNA can be removed enzymatically. We compare this method with traditional PLA on several biomarkers and show that the higher stringency for c-PLA improves reproducibility and enhances sensitivity in both buffer and human plasma. The limit of detection ranges from femtomolar to nanomolar concentrations for both methods. Kinetic analyses using surface plasmon resonance (SPR) and biolayer interferometry (BLI) reveal that the variation in limit of detection is due to the variation in antibody affinity and that c-PLA outperforms traditional PLA for low-affinity antibodies. The lower background signal can be used to increase proximity probe concentration while maintaining a high signal-to-noise ratio, thereby enabling the use of low-affinity reagents in a homogeneous assay format. We anticipate that the advantages of c-PLA will be useful in a variety of clinical protein detection applications where high-affinity reagents are lacking.}, } @article {pmid29339494, year = {2018}, author = {Gregor, C and Gwosch, KC and Sahl, SJ and Hell, SW}, title = {Strongly enhanced bacterial bioluminescence with the ilux operon for single-cell imaging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {962-967}, pmid = {29339494}, issn = {1091-6490}, mesh = {Anti-Bacterial Agents/pharmacology ; Escherichia coli/drug effects/genetics/metabolism ; Genes, Bacterial ; Luciferases, Bacterial/*genetics/*metabolism ; Luminescent Measurements ; Mutagenesis, Site-Directed ; Operon ; Photorhabdus/enzymology/genetics ; Recombinant Proteins/genetics/metabolism ; Single-Cell Analysis ; }, abstract = {Bioluminescence imaging of single cells is often complicated by the requirement of exogenous luciferins that can be poorly cell-permeable or produce high background signal. Bacterial bioluminescence is unique in that it uses reduced flavin mononucleotide as a luciferin, which is abundant in all cells, making this system purely genetically encodable by the lux operon. Unfortunately, the use of bacterial bioluminescence has been limited by its low brightness compared with other luciferases. Here, we report the generation of an improved lux operon named ilux with an approximately sevenfold increased brightness when expressed in Escherichia coli; ilux can be used to image single E. coli cells with enhanced spatiotemporal resolution over several days. In addition, since only metabolically active cells produce bioluminescent signal, we show that ilux can be used to observe the effect of different antibiotics on cell viability on the single-cell level.}, } @article {pmid29339493, year = {2018}, author = {Shafer, P and García-Fernández, P and Aguado-Puente, P and Damodaran, AR and Yadav, AK and Nelson, CT and Hsu, SL and Wojdeł, JC and Íñiguez, J and Martin, LW and Arenholz, E and Junquera, J and Ramesh, R}, title = {Emergent chirality in the electric polarization texture of titanate superlattices.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {915-920}, pmid = {29339493}, issn = {1091-6490}, abstract = {Chirality is a geometrical property by which an object is not superimposable onto its mirror image, thereby imparting a handedness. Chirality determines many important properties in nature-from the strength of the weak interactions according to the electroweak theory in particle physics to the binding of enzymes with naturally occurring amino acids or sugars, reactions that are fundamental for life. In condensed matter physics, the prediction of topologically protected magnetic skyrmions and related spin textures in chiral magnets has stimulated significant research. If the magnetic dipoles were replaced by their electrical counterparts, then electrically controllable chiral devices could be designed. Complex oxide BaTiO3/SrTiO3 nanocomposites and PbTiO3/SrTiO3 superlattices are perfect candidates, since "polar vortices," in which a continuous rotation of ferroelectric polarization spontaneously forms, have been recently discovered. Using resonant soft X-ray diffraction, we report the observation of a strong circular dichroism from the interaction between circularly polarized light and the chiral electric polarization texture that emerges in PbTiO3/SrTiO3 superlattices. This hallmark of chirality is explained by a helical rotation of electric polarization that second-principles simulations predict to reside within complex 3D polarization textures comprising ordered topological line defects. The handedness of the texture can be topologically characterized by the sign of the helicity number of the chiral line defects. This coupling between the optical and novel polar properties could be exploited to encode chiral signatures into photon or electron beams for information processing.}, } @article {pmid29339492, year = {2018}, author = {Yi, T and Wagner, G}, title = {Cytocapsular tubes conduct cell translocation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {E1137-E1146}, pmid = {29339492}, issn = {1091-6490}, support = {R01 CA200913/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Cell Membrane/*metabolism/ultrastructure ; Cell Movement/*physiology ; Cell Surface Extensions/*metabolism/ultrastructure ; Cells, Cultured ; Eukaryotic Initiation Factor-4E/*metabolism ; Female ; Humans ; Mammary Glands, Animal/cytology/*physiology ; Mammary Glands, Human/cytology/*physiology ; Mice ; Mice, Inbred NOD ; Mice, SCID ; Microscopy, Electron, Scanning ; Organelles/metabolism/ultrastructure ; Protein Biosynthesis ; }, abstract = {Cell locomotion is essential for multicellular organism embryo development, organ homeostasis, tissue regeneration, immune responses, and tumor metastasis. Here we report that single mammalian cells can generate two extracellular membranous compartments: cytocapsulae and cytocapsular tubes. Cells migrate in cytocapsulae and engender cytocapsular tubes, which exhibit pleiotropic biological functions and provide tubular routes for directed cell transportation. Ultrastructural analysis by electron microscope revealed that nanoprotrusions surround and anchor cytocapsular tubes in place. Multiple cytocapsular tubes interconnect and form networks supporting directed cell transportation in diverse directions. Enhanced translation initiation factor eIF4E up-regulates translation of transcripts encoding proteins important for organelle development. Thus, this study proposes a mechanism of directed cell translocation in cytocapsular tubes, which may facilitate the management of diseases, including tumor metastasis.}, } @article {pmid29339491, year = {2018}, author = {Geng, Y and Michowski, W and Chick, JM and Wang, YE and Jecrois, ME and Sweeney, KE and Liu, L and Han, RC and Ke, N and Zagozdzon, A and Sicinska, E and Bronson, RT and Gygi, SP and Sicinski, P}, title = {Kinase-independent function of E-type cyclins in liver cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1015-1020}, pmid = {29339491}, issn = {1091-6490}, support = {R01 CA083688/CA/NCI NIH HHS/United States ; R01 CA132740/CA/NCI NIH HHS/United States ; R01 CA190509/CA/NCI NIH HHS/United States ; R01 CA202634/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Carcinogenesis/genetics/metabolism ; Cell Line, Tumor ; Cell Proliferation ; Cyclin E/deficiency/genetics/*metabolism ; Cyclin-Dependent Kinase 2/metabolism ; Cyclins/deficiency/genetics/metabolism ; Disease Progression ; Female ; Humans ; Liver Neoplasms/genetics/*metabolism ; Liver Neoplasms, Experimental/genetics/metabolism/pathology ; Male ; Mice ; Mice, Knockout ; Oncogene Proteins/deficiency/genetics/metabolism ; }, abstract = {E-type cyclins (cyclins E1 and E2) are components of the core cell cycle machinery and are overexpressed in many human tumor types. E cyclins are thought to drive tumor cell proliferation by activating the cyclin-dependent kinase 2 (CDK2). The cyclin E1 gene represents the site of recurrent integration of the hepatitis B virus in the pathogenesis of hepatocellular carcinoma, and this event is associated with strong up-regulation of cyclin E1 expression. Regardless of the underlying mechanism of tumorigenesis, the majority of liver cancers overexpress E-type cyclins. Here we used conditional cyclin E knockout mice and a liver cancer model to test the requirement for the function of E cyclins in liver tumorigenesis. We show that a ubiquitous, global shutdown of E cyclins did not visibly affect postnatal development or physiology of adult mice. However, an acute ablation of E cyclins halted liver cancer progression. We demonstrated that also human liver cancer cells critically depend on E cyclins for proliferation. In contrast, we found that the function of the cyclin E catalytic partner, CDK2, is dispensable in liver cancer cells. We observed that E cyclins drive proliferation of tumor cells in a CDK2- and kinase-independent mechanism. Our study suggests that compounds which degrade or inhibit cyclin E might represent a highly selective therapeutic strategy for patients with liver cancer, as these compounds would selectively cripple proliferation of tumor cells, while sparing normal tissues.}, } @article {pmid29339490, year = {2018}, author = {Tong, J and Manik, MK and Im, YJ}, title = {Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E856-E865}, pmid = {29339490}, issn = {1091-6490}, mesh = {Animals ; Binding Sites ; Biological Transport ; Carrier Proteins/*metabolism ; Cell Membrane/*metabolism ; Crystallography, X-Ray ; Endoplasmic Reticulum/metabolism ; Ergosterol/chemistry ; Escherichia coli/metabolism ; Green Fluorescent Proteins/metabolism ; Hydrophobic and Hydrophilic Interactions ; Ligands ; Lipids/chemistry ; Liposomes/chemistry ; Mice ; Mitochondria ; Mitochondrial Membranes/metabolism ; Pleckstrin Homology Domains ; Protein Binding ; Protein Domains ; Protein Structure, Secondary ; Sterols/*chemistry ; Yeasts/metabolism ; }, abstract = {Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal α-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Ω1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Ω1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites.}, } @article {pmid29339489, year = {2018}, author = {Dematteis, G and Grafke, T and Vanden-Eijnden, E}, title = {Rogue waves and large deviations in deep sea.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {855-860}, pmid = {29339489}, issn = {1091-6490}, abstract = {The appearance of rogue waves in deep sea is investigated by using the modified nonlinear Schrödinger (MNLS) equation in one spatial dimension with random initial conditions that are assumed to be normally distributed, with a spectrum approximating realistic conditions of a unidirectional sea state. It is shown that one can use the incomplete information contained in this spectrum as prior and supplement this information with the MNLS dynamics to reliably estimate the probability distribution of the sea surface elevation far in the tail at later times. Our results indicate that rogue waves occur when the system hits unlikely pockets of wave configurations that trigger large disturbances of the surface height. The rogue wave precursors in these pockets are wave patterns of regular height, but with a very specific shape that is identified explicitly, thereby allowing for early detection. The method proposed here combines Monte Carlo sampling with tools from large deviations theory that reduce the calculation of the most likely rogue wave precursors to an optimization problem that can be solved efficiently. This approach is transferable to other problems in which the system's governing equations contain random initial conditions and/or parameters.}, } @article {pmid29339488, year = {2018}, author = {Grasland-Mongrain, P and Zorgani, A and Nakagawa, S and Bernard, S and Paim, LG and Fitzharris, G and Catheline, S and Cloutier, G}, title = {Ultrafast imaging of cell elasticity with optical microelastography.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {861-866}, pmid = {29339488}, issn = {1091-6490}, support = {MOP-84358//CIHR/Canada ; MOP-142334//CIHR/Canada ; }, mesh = {Algorithms ; Animals ; Biomechanical Phenomena ; Computer Simulation ; Elastic Modulus ; Elasticity/*physiology ; Elasticity Imaging Techniques/instrumentation/*methods ; Female ; Finite Element Analysis ; Image Processing, Computer-Assisted/methods ; Mice ; Models, Biological ; Oocytes/cytology/physiology ; Vibration ; }, abstract = {Elasticity is a fundamental cellular property that is related to the anatomy, functionality, and pathological state of cells and tissues. However, current techniques based on cell deformation, atomic force microscopy, or Brillouin scattering are rather slow and do not always accurately represent cell elasticity. Here, we have developed an alternative technique by applying shear wave elastography to the micrometer scale. Elastic waves were mechanically induced in live mammalian oocytes using a vibrating micropipette. These audible frequency waves were observed optically at 200,000 frames per second and tracked with an optical flow algorithm. Whole-cell elasticity was then mapped using an elastography method inspired by the seismology field. Using this approach we show that the elasticity of mouse oocytes is decreased when the oocyte cytoskeleton is disrupted with cytochalasin B. The technique is fast (less than 1 ms for data acquisition), precise (spatial resolution of a few micrometers), able to map internal cell structures, and robust and thus represents a tractable option for interrogating biomechanical properties of diverse cell types.}, } @article {pmid29339487, year = {2018}, author = {Zhang, W and Villarini, G}, title = {Uncovering the role of the East Asian jet stream and heterogeneities in atmospheric rivers affecting the western United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {891-896}, doi = {10.1073/pnas.1717883115}, pmid = {29339487}, issn = {1091-6490}, abstract = {Atmospheric rivers (ARs) exert major socioeconomic repercussions along the US West Coast by inducing heavy rainfall, flooding, strong winds, and storm surge. Despite the significant societal and economic repercussions of these storms, our understanding of the physical drivers responsible for their interannual variability is limited, with different climate modes identified as possible mechanisms. Here we show that the Pacific-Japan (PJ) teleconnections/patterns and the East Asian subtropical jet (EASJ) exhibit a strong linkage with the total frequency of ARs making landfall over the western United States, much stronger than the other potential climate modes previously considered. While our findings indicate that the PJ pattern and EASJ are the most relevant climate modes driving the overall AR activity, we also uncover heterogeneities in AR tracks. Specifically, we show that not all ARs making landfall along the West Coast come from a single population, but rather that it is possible to stratify these storms into three clusters. While the PJ pattern and EASJ are major drivers of AR activity for two clusters, the cluster that primarily affects the US Southwest is largely driven by other climate modes [El Niño Southern Oscillation (ENSO), the Atlantic meridional mode (AMM), the Pacific-North America (PNA) teleconnection pattern, and the North Pacific Gyre Oscillation (NPGO)]. Therefore, important regional differences exist and this information can substantially enhance our ability to predict and prepare for these storms and their impacts.}, } @article {pmid29339486, year = {2018}, author = {Heshmati, M and Aleyasin, H and Menard, C and Christoffel, DJ and Flanigan, ME and Pfau, ML and Hodes, GE and Lepack, AE and Bicks, LK and Takahashi, A and Chandra, R and Turecki, G and Lobo, MK and Maze, I and Golden, SA and Russo, SJ}, title = {Cell-type-specific role for nucleus accumbens neuroligin-2 in depression and stress susceptibility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1111-1116}, pmid = {29339486}, issn = {1091-6490}, support = {FI2 GM117583/GM/NIGMS NIH HHS/United States ; F31 MH105217/MH/NIMH NIH HHS/United States ; F30 MH100835/MH/NIMH NIH HHS/United States ; T32 MH087004/MH/NIMH NIH HHS/United States ; P50 MH096890/MH/NIMH NIH HHS/United States ; R01 MH114882/MH/NIMH NIH HHS/United States ; R01 MH090264/MH/NIMH NIH HHS/United States ; P50 AT008661/AT/NCCIH NIH HHS/United States ; R01 MH106500/MH/NIMH NIH HHS/United States ; T32 MH096678/MH/NIMH NIH HHS/United States ; }, mesh = {Aggression ; Animals ; Antidepressive Agents/pharmacology ; Behavior, Animal ; Cell Adhesion Molecules, Neuronal/*metabolism ; Cell Line ; Depressive Disorder, Major/*physiopathology ; Disease Models, Animal ; *Dominance-Subordination ; Heterozygote ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Transgenic ; MicroRNAs/metabolism ; Nerve Tissue Proteins/*metabolism ; Nucleus Accumbens/*metabolism ; RNA, Messenger/metabolism ; Receptors, Dopamine D1/metabolism ; Receptors, Dopamine D2/metabolism ; Social Behavior ; Stress, Psychological/*physiopathology ; Synapses/metabolism ; }, abstract = {Behavioral coping strategies are critical for active resilience to stress and depression; here we describe a role for neuroligin-2 (NLGN-2) in the nucleus accumbens (NAc). Neuroligins (NLGN) are a family of neuronal postsynaptic cell adhesion proteins that are constituents of the excitatory and inhibitory synapse. Importantly, NLGN-3 and NLGN-4 mutations are strongly implicated as candidates underlying the development of neuropsychiatric disorders with social disturbances such as autism, but the role of NLGN-2 in neuropsychiatric disease states is unclear. Here we show a reduction in NLGN-2 gene expression in the NAc of patients with major depressive disorder. Chronic social defeat stress in mice also decreases NLGN-2 selectively in dopamine D1-positive cells, but not dopamine D2-positive cells, within the NAc of stress-susceptible mice. Functional NLGN-2 knockdown produces bidirectional, cell-type-specific effects: knockdown in dopamine D1-positive cells promotes subordination and stress susceptibility, whereas knockdown in dopamine D2-positive cells mediates active defensive behavior. These findings establish a behavioral role for NAc NLGN-2 in stress and depression; provide a basis for targeted, cell-type specific therapy; and highlight the role of active behavioral coping mechanisms in stress susceptibility.}, } @article {pmid29339485, year = {2018}, author = {Han, J and Jackson, D and Holm, J and Turner, K and Ashcraft, P and Wang, X and Cook, B and Arning, E and Genta, RM and Venuprasad, K and Souza, RF and Sweetman, L and Theiss, AL}, title = {Elevated d-2-hydroxyglutarate during colitis drives progression to colorectal cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1057-1062}, pmid = {29339485}, issn = {1091-6490}, mesh = {Animals ; Apoptosis ; Azoxymethane/chemistry ; Biomarkers, Tumor/metabolism ; Biopsy ; Caco-2 Cells ; Cell Movement ; Cell Proliferation ; Cell Survival ; Colitis/*metabolism/*pathology ; Colitis, Ulcerative/metabolism/pathology ; Colorectal Neoplasms/*metabolism/*pathology ; Dextran Sulfate/chemistry ; Disease Progression ; Glutarates/*metabolism ; Humans ; Hypoxia-Inducible Factor 1, alpha Subunit/metabolism ; Inflammation ; Intestinal Mucosa/pathology ; Mice ; Risk ; }, abstract = {d-2-hydroxyglutarate (D2HG) is produced in the tricarboxylic acid cycle and is quickly converted to α-ketoglutarate by d-2-hydroxyglutarate dehydrogenase (D2HGDH). In a mouse model of colitis-associated colon cancer (CAC), urine level of D2HG during colitis correlates positively with subsequent polyp counts and severity of dysplasia. The i.p. injection of D2HG results in delayed recovery from colitis and severe tumorigenesis. The colonic expression of D2HGDH is decreased in ulcerative colitis (UC) patients at baseline who progress to cancer. Hypoxia-inducible factor (Hif)-1α is a key regulator of D2HGDH transcription. Our study identifies urine D2HG and tissue D2HGDH expression as biomarkers to identify patients at risk for progressing from colitis to cancer. The D2HG/D2HGDH pathway provides potential therapeutic targets for the treatment of CAC.}, } @article {pmid29339484, year = {2018}, author = {Wilhelm, D and Bruck, J and Qian, L}, title = {Probabilistic switching circuits in DNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {903-908}, pmid = {29339484}, issn = {1091-6490}, abstract = {A natural feature of molecular systems is their inherent stochastic behavior. A fundamental challenge related to the programming of molecular information processing systems is to develop a circuit architecture that controls the stochastic states of individual molecular events. Here we present a systematic implementation of probabilistic switching circuits, using DNA strand displacement reactions. Exploiting the intrinsic stochasticity of molecular interactions, we developed a simple, unbiased DNA switch: An input signal strand binds to the switch and releases an output signal strand with probability one-half. Using this unbiased switch as a molecular building block, we designed DNA circuits that convert an input signal to an output signal with any desired probability. Further, this probability can be switched between 2 n different values by simply varying the presence or absence of n distinct DNA molecules. We demonstrated several DNA circuits that have multiple layers and feedback, including a circuit that converts an input strand to an output strand with eight different probabilities, controlled by the combination of three DNA molecules. These circuits combine the advantages of digital and analog computation: They allow a small number of distinct input molecules to control a diverse signal range of output molecules, while keeping the inputs robust to noise and the outputs at precise values. Moreover, arbitrarily complex circuit behaviors can be implemented with just a single type of molecular building block.}, } @article {pmid29339483, year = {2018}, author = {Jenness, C and Giunta, S and Müller, MM and Kimura, H and Muir, TW and Funabiki, H}, title = {HELLS and CDCA7 comprise a bipartite nucleosome remodeling complex defective in ICF syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E876-E885}, pmid = {29339483}, issn = {1091-6490}, support = {R01 GM075249/GM/NIGMS NIH HHS/United States ; R01 GM107047/GM/NIGMS NIH HHS/United States ; R37 GM086868/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Aurora Kinase B/metabolism ; Cell Cycle ; Chromatin/chemistry ; Cluster Analysis ; DNA (Cytosine-5-)-Methyltransferases/genetics ; DNA Helicases/genetics/*metabolism ; DNA Methylation ; Face/*abnormalities ; HeLa Cells ; Histones/metabolism ; Humans ; Immunologic Deficiency Syndromes/*genetics ; *Mutation ; Nuclear Proteins/genetics/*metabolism ; Nucleosomes/chemistry ; Ovum/metabolism ; Peptides/chemistry ; Protein Binding ; Protein Domains ; Proteomics ; RNA Interference ; Xenopus laevis ; }, abstract = {Mutations in CDCA7, the SNF2 family protein HELLS (LSH), or the DNA methyltransferase DNMT3b cause immunodeficiency-centromeric instability-facial anomalies (ICF) syndrome. While it has been speculated that DNA methylation defects cause this disease, little is known about the molecular function of CDCA7 and its functional relationship to HELLS and DNMT3b. Systematic analysis of how the cell cycle, H3K9 methylation, and the mitotic kinase Aurora B affect proteomic profiles of chromatin in Xenopus egg extracts revealed that HELLS and CDCA7 form a stoichiometric complex on chromatin, in a manner sensitive to Aurora B. Although HELLS alone fails to remodel nucleosomes, we demonstrate that the HELLS-CDCA7 complex possesses nucleosome remodeling activity. Furthermore, CDCA7 is essential for loading HELLS onto chromatin, and CDCA7 harboring patient ICF mutations fails to recruit the complex to chromatin. Together, our study identifies a unique bipartite nucleosome remodeling complex where the functional remodeling activity is split between two proteins and thus delineates the defective pathway in ICF syndrome.}, } @article {pmid29339482, year = {2018}, author = {Liu, F and Choi, D and Xie, L and Roeder, K}, title = {Global spectral clustering in dynamic networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {927-932}, pmid = {29339482}, issn = {1091-6490}, support = {R01 MH109900/MH/NIMH NIH HHS/United States ; R37 MH057881/MH/NIMH NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; *Cluster Analysis ; Computer Simulation ; Gene Expression Regulation, Developmental ; *Gene Regulatory Networks ; Macaca mulatta ; Models, Genetic ; Models, Neurological ; Models, Statistical ; Prefrontal Cortex/embryology/growth & development/metabolism ; }, abstract = {Community detection is challenging when the network structure is estimated with uncertainty. Dynamic networks present additional challenges but also add information across time periods. We propose a global community detection method, persistent communities by eigenvector smoothing (PisCES), that combines information across a series of networks, longitudinally, to strengthen the inference for each period. Our method is derived from evolutionary spectral clustering and degree correction methods. Data-driven solutions to the problem of tuning parameter selection are provided. In simulations we find that PisCES performs better than competing methods designed for a low signal-to-noise ratio. Recently obtained gene expression data from rhesus monkey brains provide samples from finely partitioned brain regions over a broad time span including pre- and postnatal periods. Of interest is how gene communities develop over space and time; however, once the data are divided into homogeneous spatial and temporal periods, sample sizes are very small, making inference quite challenging. Applying PisCES to medial prefrontal cortex in monkey rhesus brains from near conception to adulthood reveals dense communities that persist, merge, and diverge over time and others that are loosely organized and short lived, illustrating how dynamic community detection can yield interesting insights into processes such as brain development.}, } @article {pmid29339481, year = {2018}, author = {Kim, YK and Saver, M and Simon, J and Kent, CF and Shao, L and Eddison, M and Agrawal, P and Texada, M and Truman, JW and Heberlein, U}, title = {Repetitive aggressive encounters generate a long-lasting internal state in Drosophila melanogaster males.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1099-1104}, pmid = {29339481}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Aggression/*physiology ; Animals ; Behavior, Animal/*physiology ; Cluster Analysis ; Competitive Behavior ; Crosses, Genetic ; Drosophila melanogaster/*physiology ; Female ; Male ; Memory ; Movement ; Neurons/metabolism ; Odorants ; Olfactory Bulb ; Risk-Taking ; Sexual Behavior, Animal/*physiology ; Time Factors ; }, abstract = {Multiple studies have investigated the mechanisms of aggressive behavior in Drosophila; however, little is known about the effects of chronic fighting experience. Here, we investigated if repeated fighting encounters would induce an internal state that could affect the expression of subsequent behavior. We trained wild-type males to become winners or losers by repeatedly pairing them with hypoaggressive or hyperaggressive opponents, respectively. As described previously, we observed that chronic losers tend to lose subsequent fights, while chronic winners tend to win them. Olfactory conditioning experiments showed that winning is perceived as rewarding, while losing is perceived as aversive. Moreover, the effect of chronic fighting experience generalized to other behaviors, such as gap-crossing and courtship. We propose that in response to repeatedly winning or losing aggressive encounters, male flies form an internal state that displays persistence and generalization; fight outcomes can also have positive or negative valence. Furthermore, we show that the activities of the PPL1-γ1pedc dopaminergic neuron and the MBON-γ1pedc>α/β mushroom body output neuron are required for aversion to an olfactory cue associated with losing fights.}, } @article {pmid29339480, year = {2018}, author = {Huo, YJ and Dovidio, JF and Jiménez, TR and Schildkraut, DJ}, title = {Local policy proposals can bridge Latino and (most) white Americans' response to immigration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {945-950}, pmid = {29339480}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Arizona ; Attitude ; Emigrants and Immigrants/*legislation & jurisprudence/*psychology ; Emigration and Immigration/*legislation & jurisprudence ; European Continental Ancestry Group/psychology ; Female ; Hispanic Americans/psychology ; Humans ; Male ; Middle Aged ; New Mexico ; *Public Policy ; Surveys and Questionnaires ; United States ; Young Adult ; }, abstract = {In the past 15 years, the adoption of subnational immigration policies in the United States, such as those established by individual states, has gone from nearly zero to over 300 per year. These include welcoming policies aimed at attracting and incorporating immigrants, as well as unwelcoming policies directed at denying immigrants access to public resources and services. Using data from a 2016 random digit-dialing telephone survey with an embedded experiment, we examine whether institutional support for policies that are either welcoming or hostile toward immigrants differentially shape Latinos' and whites' feelings of belonging in their state (Arizona/New Mexico, adjacent states with contrasting immigration policies). We randomly assigned individuals from the representative sample (n = 1,903) of Latinos (US and foreign born) and whites (all US born) to consider policies that were either welcoming of or hostile toward immigrants. Across both states of residence, Latinos, especially those foreign born, regardless of citizenship, expressed more positive affect and greater belonging when primed with a welcoming (vs. hostile) policy. Demonstrating the importance of local norms, these patterns held among US-born whites, except among self-identified politically conservative whites, who showed more negative affect and lower levels of belonging in response to welcoming policies. Thus, welcoming immigration policies, supported by institutional authorities, can create a sense of belonging not only among newcomers that is vital to successful integration but also among a large segment of the population that is not a direct beneficiary of such policies-US-born whites.}, } @article {pmid29339479, year = {2018}, author = {Devignes, CS and Aslan, Y and Brenot, A and Devillers, A and Schepers, K and Fabre, S and Chou, J and Casbon, AJ and Werb, Z and Provot, S}, title = {HIF signaling in osteoblast-lineage cells promotes systemic breast cancer growth and metastasis in mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E992-E1001}, pmid = {29339479}, issn = {1091-6490}, support = {T32 GM007618/GM/NIGMS NIH HHS/United States ; R01 CA180039/CA/NCI NIH HHS/United States ; U01 CA199315/CA/NCI NIH HHS/United States ; T32 CA108462/CA/NCI NIH HHS/United States ; R01 CA057621/CA/NCI NIH HHS/United States ; }, mesh = {Alleles ; Amino Acid Motifs ; Animals ; Bone Neoplasms/secondary ; Bone and Bones/metabolism ; Cell Lineage ; Chemokine CXCL12/blood ; Disease Progression ; Female ; Green Fluorescent Proteins/metabolism ; Hypoxia ; Hypoxia-Inducible Factor 1, alpha Subunit/*genetics/*metabolism ; Ligands ; Mammary Neoplasms, Experimental/*genetics/*metabolism ; Mice ; Mice, Transgenic ; Neoplasm Metastasis ; Osteoblasts/*metabolism ; Osteoclasts/metabolism ; Signal Transduction ; }, abstract = {Bone metastasis involves dynamic interplay between tumor cells and the local stromal environment. In bones, local hypoxia and activation of the hypoxia-inducible factor (HIF)-1α in osteoblasts are essential to maintain skeletal homeostasis. However, the role of osteoblast-specific HIF signaling in cancer metastasis is unknown. Here, we show that osteoprogenitor cells (OPCs) are located in hypoxic niches in the bone marrow and that activation of HIF signaling in these cells increases bone mass and favors breast cancer metastasis to bone locally. Remarkably, HIF signaling in osteoblast-lineage cells also promotes breast cancer growth and dissemination remotely, in the lungs and in other tissues distant from bones. Mechanistically, we found that activation of HIF signaling in OPCs increases blood levels of the chemokine C-X-C motif ligand 12 (CXCL12), which leads to a systemic increase of breast cancer cell proliferation and dissemination through direct activation of the CXCR4 receptor. Hence, our data reveal a previously unrecognized role of the hypoxic osteogenic niche in promoting tumorigenesis beyond the local bone microenvironment. They also support the concept that the skeleton is an important regulator of the systemic tumor environment.}, } @article {pmid29339478, year = {2018}, author = {Melamed, D and Harrell, A and Simpson, B}, title = {Cooperation, clustering, and assortative mixing in dynamic networks.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {951-956}, pmid = {29339478}, issn = {1091-6490}, mesh = {Altruism ; Choice Behavior ; Cluster Analysis ; *Cooperative Behavior ; Female ; Humans ; Interpersonal Relations ; Linear Models ; Male ; Prisoner Dilemma ; *Social Networking ; }, abstract = {Humans' propensity to cooperate is driven by our embeddedness in social networks. A key mechanism through which networks promote cooperation is clustering. Within clusters, conditional cooperators are insulated from exploitation by noncooperators, allowing them to reap the benefits of cooperation. Dynamic networks, where ties can be shed and new ties formed, allow for the endogenous emergence of clusters of cooperators. Although past work suggests that either reputation processes or network dynamics can increase clustering and cooperation, existing work on network dynamics conflates reputations and dynamics. Here we report results from a large-scale experiment (total n = 2,675) that embedded participants in clustered or random networks that were static or dynamic, with varying levels of reputational information. Results show that initial network clustering predicts cooperation in static networks, but not in dynamic ones. Further, our experiment shows that while reputations are important for partner choice, cooperation levels are driven purely by dynamics. Supplemental conditions confirmed this lack of a reputation effect. Importantly, we find that when participants make individual choices to cooperate or defect with each partner, as opposed to a single decision that applies to all partners (as is standard in the literature on cooperation in networks), cooperation rates in static networks are as high as cooperation rates in dynamic networks. This finding highlights the importance of structured relations for sustained cooperation, and shows how giving experimental participants more realistic choices has important consequences for whether dynamic networks promote higher levels of cooperation than static networks.}, } @article {pmid29339477, year = {2018}, author = {Takamatsu, Y and Kolesnikova, L and Becker, S}, title = {Ebola virus proteins NP, VP35, and VP24 are essential and sufficient to mediate nucleocapsid transport.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1075-1080}, pmid = {29339477}, issn = {1091-6490}, mesh = {Antiviral Agents/chemistry ; Cell Line, Tumor ; Cytoplasm/metabolism ; Ebolavirus/metabolism ; Glycoproteins/metabolism ; Green Fluorescent Proteins/metabolism ; HEK293 Cells ; Humans ; Luminescent Proteins/metabolism ; Nucleocapsid/*metabolism ; Viral Proteins/*metabolism ; Viral Regulatory and Accessory Proteins/*metabolism ; }, abstract = {The intracytoplasmic movement of nucleocapsids is a crucial step in the life cycle of enveloped viruses. Determination of the viral components necessary for viral nucleocapsid transport competency is complicated by the dynamic and complex nature of nucleocapsid assembly and the lack of appropriate model systems. Here, we established a live-cell imaging system based on the ectopic expression of fluorescent Ebola virus (EBOV) fusion proteins, allowing the visualization and analysis of the movement of EBOV nucleocapsid-like structures with different protein compositions. Only three of the five EBOV nucleocapsid proteins-nucleoprotein, VP35, and VP24-were necessary and sufficient to form transport-competent nucleocapsid-like structures. The transport of these structures was found to be dependent on actin polymerization and to have dynamics that were undistinguishable from those of nucleocapsids in EBOV-infected cells. The intracytoplasmic movement of nucleocapsid-like structures was completely independent of the viral matrix protein VP40 and the viral surface glycoprotein GP. However, VP40 greatly enhanced the efficiency of nucleocapsid recruitment into filopodia, the sites of EBOV budding.}, } @article {pmid29339476, year = {2018}, author = {Wixted, JT and Goldinger, SD and Squire, LR and Kuhn, JR and Papesh, MH and Smith, KA and Treiman, DM and Steinmetz, PN}, title = {Coding of episodic memory in the human hippocampus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1093-1098}, pmid = {29339476}, issn = {1091-6490}, support = {F31 DC009781/DC/NIDCD NIH HHS/United States ; I01 CX000359/CX/CSRD VA/United States ; R01 HD075800/HD/NICHD NIH HHS/United States ; }, mesh = {Action Potentials/physiology ; Adult ; Amygdala/physiology ; Behavior ; Brain Mapping ; Computer Simulation ; Epilepsy/*physiopathology ; Female ; Hippocampus/*anatomy & histology/*physiology ; Humans ; Male ; *Memory, Episodic ; Middle Aged ; Neurons/metabolism/physiology ; Neurosciences ; Temporal Lobe/physiology ; Young Adult ; }, abstract = {Neurocomputational models have long posited that episodic memories in the human hippocampus are represented by sparse, stimulus-specific neural codes. A concomitant proposal is that when sparse-distributed neural assemblies become active, they suppress the activity of competing neurons (neural sharpening). We investigated episodic memory coding in the hippocampus and amygdala by measuring single-neuron responses from 20 epilepsy patients (12 female) undergoing intracranial monitoring while they completed a continuous recognition memory task. In the left hippocampus, the distribution of single-neuron activity indicated that only a small fraction of neurons exhibited strong responding to a given repeated word and that each repeated word elicited strong responding in a different small fraction of neurons. This finding reflects sparse distributed coding. The remaining large fraction of neurons exhibited a concurrent reduction in firing rates relative to novel words. The observed pattern accords with longstanding predictions that have previously received scant support from single-cell recordings from human hippocampus.}, } @article {pmid29339475, year = {2018}, author = {Liu, TH and Zhou, J and Li, M and Ding, Z and Song, Q and Liao, B and Fu, L and Chen, G}, title = {Electron mean-free-path filtering in Dirac material for improved thermoelectric performance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {879-884}, pmid = {29339475}, issn = {1091-6490}, abstract = {Recent advancements in thermoelectric materials have largely benefited from various approaches, including band engineering and defect optimization, among which the nanostructuring technique presents a promising way to improve the thermoelectric figure of merit (zT) by means of reducing the characteristic length of the nanostructure, which relies on the belief that phonons' mean free paths (MFPs) are typically much longer than electrons'. Pushing the nanostructure sizes down to the length scale dictated by electron MFPs, however, has hitherto been overlooked as it inevitably sacrifices electrical conduction. Here we report through ab initio simulations that Dirac material can overcome this limitation. The monotonically decreasing trend of the electron MFP allows filtering of long-MFP electrons that are detrimental to the Seebeck coefficient, leading to a dramatically enhanced power factor. Using SnTe as a material platform, we uncover this MFP filtering effect as arising from its unique nonparabolic Dirac band dispersion. Room-temperature zT can be enhanced by nearly a factor of 3 if one designs nanostructures with grain sizes of ∼10 nm. Our work broadens the scope of the nanostructuring approach for improving the thermoelectric performance, especially for materials with topologically nontrivial electronic dynamics.}, } @article {pmid29339474, year = {2018}, author = {Beaty, RE and Kenett, YN and Christensen, AP and Rosenberg, MD and Benedek, M and Chen, Q and Fink, A and Qiu, J and Kwapil, TR and Kane, MJ and Silvia, PJ}, title = {Robust prediction of individual creative ability from brain functional connectivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1087-1092}, pmid = {29339474}, issn = {1091-6490}, mesh = {Adult ; Behavior ; Brain/anatomy & histology/*physiology ; Brain Mapping/*methods ; Cognition ; Connectome/*methods ; *Creativity ; Female ; Humans ; Linear Models ; Magnetic Resonance Imaging ; Male ; Nerve Net ; *Thinking ; Young Adult ; }, abstract = {People's ability to think creatively is a primary means of technological and cultural progress, yet the neural architecture of the highly creative brain remains largely undefined. Here, we employed a recently developed method in functional brain imaging analysis-connectome-based predictive modeling-to identify a brain network associated with high-creative ability, using functional magnetic resonance imaging (fMRI) data acquired from 163 participants engaged in a classic divergent thinking task. At the behavioral level, we found a strong correlation between creative thinking ability and self-reported creative behavior and accomplishment in the arts and sciences (r = 0.54). At the neural level, we found a pattern of functional brain connectivity related to high-creative thinking ability consisting of frontal and parietal regions within default, salience, and executive brain systems. In a leave-one-out cross-validation analysis, we show that this neural model can reliably predict the creative quality of ideas generated by novel participants within the sample. Furthermore, in a series of external validation analyses using data from two independent task fMRI samples and a large task-free resting-state fMRI sample, we demonstrate robust prediction of individual creative thinking ability from the same pattern of brain connectivity. The findings thus reveal a whole-brain network associated with high-creative ability comprised of cortical hubs within default, salience, and executive systems-intrinsic functional networks that tend to work in opposition-suggesting that highly creative people are characterized by the ability to simultaneously engage these large-scale brain networks.}, } @article {pmid29339473, year = {2018}, author = {Nagaraj, K and Lapkina-Gendler, L and Sarfstein, R and Gurwitz, D and Pasmanik-Chor, M and Laron, Z and Yakar, S and Werner, H}, title = {Identification of thioredoxin-interacting protein (TXNIP) as a downstream target for IGF1 action.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1045-1050}, pmid = {29339473}, issn = {1091-6490}, mesh = {Animals ; Carrier Proteins/genetics/*metabolism ; Cell Line ; Gene Expression ; Glucose/metabolism ; Humans ; Insulin/metabolism ; Insulin-Like Growth Factor I/genetics/*metabolism ; Laron Syndrome/genetics/*metabolism ; Male ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Neoplasms/genetics/metabolism/prevention & control ; Oxidative Stress ; Promoter Regions, Genetic ; RNA, Messenger/genetics/metabolism ; }, abstract = {Laron syndrome (LS), or primary growth hormone (GH) insensitivity, is the best-characterized entity among the congenital insulin-like growth factor 1 (IGF1) deficiencies. Life-long exposure to minute endogenous IGF1 levels is linked to low stature as well as a number of endocrine and metabolic abnormalities. While elevated IGF1 is correlated with increased cancer incidence, epidemiological studies revealed that patients with LS do not develop tumors. The mechanisms associated with cancer protection in LS are yet to be discovered. Recent genomic analyses identified a series of metabolic genes that are overrepresented in patients with LS. Given the augmented expression of these genes in a low IGF1 milieu, we hypothesized that they may constitute targets for IGF1 action. Thioredoxin-interacting protein (TXNIP) plays a critical role in cellular redox control by thioredoxin. TXNIP serves as a glucose and oxidative stress sensor, being commonly silenced by genetic or epigenetic events in cancer cells. Consistent with its enhanced expression in LS, we provide evidence that TXNIP gene expression is negatively regulated by IGF1. These results were corroborated in animal studies. In addition, we show that oxidative and glucose stresses led to marked increases in TXNIP expression. Supplementation of IGF1 attenuated TXNIP levels, suggesting that IGF1 exerts its antiapoptotic effect via inhibition of TXNIP Augmented TXNIP expression in LS may account for cancer protection in this condition. Finally, TXNIP levels could be potentially useful in the clinic as a predictive or diagnostic biomarker for IGF1R-targeted therapies.}, } @article {pmid29339472, year = {2018}, author = {Møller, R and Schwarz, TM and Noriega, VM and Panis, M and Sachs, D and Tortorella, D and tenOever, BR}, title = {miRNA-mediated targeting of human cytomegalovirus reveals biological host and viral targets of IE2.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1069-1074}, pmid = {29339472}, issn = {1091-6490}, support = {R01 AI110575/AI/NIAID NIH HHS/United States ; R21 AI133717/AI/NIAID NIH HHS/United States ; R21 AI136553/AI/NIAID NIH HHS/United States ; }, mesh = {Computational Biology ; Cytomegalovirus/*genetics ; Fibroblasts/metabolism ; Gene Expression Regulation, Viral ; Gene Silencing ; Hematopoietic Stem Cells/cytology ; Humans ; Immediate-Early Proteins/*metabolism ; Macrophages/metabolism ; Membrane Glycoproteins/genetics ; MicroRNAs/*metabolism ; Mutation ; Myeloid Cells/metabolism ; Trans-Activators/*metabolism ; Transcriptional Activation ; Transcriptome ; Viral Envelope Proteins/genetics ; Virus Replication ; }, abstract = {Human cytomegalovirus (HCMV) impacts more than one-half of the human population owing to its capacity to manipulate the cell and create latent reservoirs in the host. Despite an extensive understanding of HCMV biology during acute infection in fibroblasts, the molecular basis for latency in myeloid cells remains incomplete. This knowledge gap is due largely to the fact that the existing genetic systems require virus rescue in fibroblasts, precluding the study of genes that are essential during acute infection, yet likely play unique roles in myeloid cells or the establishment of latency. Here we present a solution to address this restriction. Through the exploitation of a hematopoietic-specific microRNA, we demonstrate a one-step recombineering approach that enables gene silencing only in cells associated with latency. As a proof of concept, here we describe a TB40/E variant that undergoes hematopoietic targeting of the Immediate Early-2 (IE2) gene to explore its function during infection of myeloid cells. While virus replication of the hematopoietic-targeted IE2 variant was unimpaired in fibroblasts, we observed a >100-fold increase in virus titers in myeloid cells. Virus replication in myeloid cells demonstrated that IE2 has a significant transcriptional footprint on both viral and host genes. These data implicate IE2 as an essential mediator of virus biology in myeloid cells and illustrate the utility of cell-specific microRNA-based targeting.}, } @article {pmid29339471, year = {2018}, author = {Bastos, AM and Loonis, R and Kornblith, S and Lundqvist, M and Miller, EK}, title = {Laminar recordings in frontal cortex suggest distinct layers for maintenance and control of working memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1117-1122}, pmid = {29339471}, issn = {1091-6490}, support = {R37 MH087027/MH/NIMH NIH HHS/United States ; }, mesh = {Action Potentials/physiology ; Animals ; Brain Mapping/methods ; *Cognition ; Electrodes ; Frontal Lobe/*physiology ; Macaca mulatta ; *Memory, Short-Term ; Neurons/physiology ; Oscillometry ; Prefrontal Cortex/*physiology ; Visual Cortex/physiology ; }, abstract = {All of the cerebral cortex has some degree of laminar organization. These different layers are composed of neurons with distinct connectivity patterns, embryonic origins, and molecular profiles. There are little data on the laminar specificity of cognitive functions in the frontal cortex, however. We recorded neuronal spiking/local field potentials (LFPs) using laminar probes in the frontal cortex (PMd, 8A, 8B, SMA/ACC, DLPFC, and VLPFC) of monkeys performing working memory (WM) tasks. LFP power in the gamma band (50-250 Hz) was strongest in superficial layers, and LFP power in the alpha/beta band (4-22 Hz) was strongest in deep layers. Memory delay activity, including spiking and stimulus-specific gamma bursting, was predominately in superficial layers. LFPs from superficial and deep layers were synchronized in the alpha/beta bands. This was primarily unidirectional, with alpha/beta bands in deep layers driving superficial layer activity. The phase of deep layer alpha/beta modulated superficial gamma bursting associated with WM encoding. Thus, alpha/beta rhythms in deep layers may regulate the superficial layer gamma bands and hence maintenance of the contents of WM.}, } @article {pmid29339470, year = {2018}, author = {Hainmueller, J and Lawrence, D and Gest, J and Hotard, M and Koslowski, R and Laitin, DD}, title = {A randomized controlled design reveals barriers to citizenship for low-income immigrants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {939-944}, pmid = {29339470}, issn = {1091-6490}, mesh = {Costs and Cost Analysis ; *Emigrants and Immigrants/statistics & numerical data ; Emigration and Immigration/legislation & jurisprudence/statistics & numerical data ; Humans ; New York ; *Poverty/statistics & numerical data ; Public Policy/economics ; United States ; }, abstract = {Citizenship endows legal protections and is associated with economic and social gains for immigrants and their communities. In the United States, however, naturalization rates are relatively low. Yet we lack reliable knowledge as to what constrains immigrants from applying. Drawing on data from a public/private naturalization program in New York, this research provides a randomized controlled study of policy interventions that address these constraints. The study tested two programmatic interventions among low-income immigrants who are eligible for citizenship. The first randomly assigned a voucher that covers the naturalization application fee among immigrants who otherwise would have to pay the full cost of the fee. The second randomly assigned a set of behavioral nudges, similar to outreach efforts used by service providers, among immigrants whose incomes were low enough to qualify them for a federal waiver that eliminates the application fee. Offering the fee voucher increased naturalization application rates by about 41%, suggesting that application fees act as a barrier for low-income immigrants who want to become US citizens. The nudges to encourage the very poor to apply had no discernible effect, indicating the presence of nonfinancial barriers to naturalization.}, } @article {pmid29339469, year = {2018}, author = {Liu, P and Lechtreck, KF}, title = {The Bardet-Biedl syndrome protein complex is an adapter expanding the cargo range of intraflagellar transport trains for ciliary export.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E934-E943}, pmid = {29339469}, issn = {1091-6490}, support = {R01 GM110413/GM/NIGMS NIH HHS/United States ; }, mesh = {Bardet-Biedl Syndrome/*genetics/*metabolism ; Biological Transport ; Cell Membrane/metabolism ; Chlamydomonas reinhardtii/genetics/physiology ; Cilia/*metabolism ; Flagella/metabolism ; Fluorescence Recovery After Photobleaching ; Humans ; *Mutation ; Phospholipase D/metabolism ; Photochemical Processes ; Phototaxis ; Protein Domains ; Protein Transport/*genetics ; Proteins/metabolism ; Transgenes ; }, abstract = {Bardet-Biedl syndrome (BBS) is a ciliopathy resulting from defects in the BBSome, a conserved protein complex. BBSome mutations affect ciliary membrane composition, impairing cilia-based signaling. The mechanism by which the BBSome regulates ciliary membrane content remains unknown. Chlamydomonas bbs mutants lack phototaxis and accumulate phospholipase D (PLD) in the ciliary membrane. Single particle imaging revealed that PLD comigrates with BBS4 by intraflagellar transport (IFT) while IFT of PLD is abolished in bbs mutants. BBSome deficiency did not alter the rate of PLD entry into cilia. Membrane association and the N-terminal 58 residues of PLD are sufficient and necessary for BBSome-dependent transport and ciliary export. The replacement of PLD's ciliary export sequence (CES) caused PLD to accumulate in cilia of cells with intact BBSomes and IFT. The buildup of PLD inside cilia impaired phototaxis, revealing that PLD is a negative regulator of phototactic behavior. We conclude that the BBSome is a cargo adapter ensuring ciliary export of PLD on IFT trains to regulate phototaxis.}, } @article {pmid29339468, year = {2018}, author = {Vasylyeva, TI and Liulchuk, M and Friedman, SR and Sazonova, I and Faria, NR and Katzourakis, A and Babii, N and Scherbinska, A and Thézé, J and Pybus, OG and Smyrnov, P and Mbisa, JL and Paraskevis, D and Hatzakis, A and Magiorkinis, G}, title = {Molecular epidemiology reveals the role of war in the spread of HIV in Ukraine.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1051-1056}, pmid = {29339468}, issn = {1091-6490}, support = {P30 DA011041/DA/NIDA NIH HHS/United States ; DP1 DA034989/DA/NIDA NIH HHS/United States ; MR/K010565/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; MC_PC_15100/ZK/16-078//Medical Research Council/United Kingdom ; }, mesh = {Communicable Disease Control ; Epidemics ; Female ; Geography ; HIV Infections/complications/*epidemiology ; HIV-1/genetics ; Humans ; Likelihood Functions ; Male ; *Molecular Epidemiology ; Phylogeny ; Risk-Taking ; Sexual Behavior ; Substance Abuse, Intravenous/complications ; Ukraine/epidemiology ; *Warfare ; }, abstract = {Ukraine has one of the largest HIV epidemics in Europe, historically driven by people who inject drugs (PWID). The epidemic showed signs of stabilization in 2012, but the recent war in eastern Ukraine may be reigniting virus spread. We investigated the movement of HIV-infected people within Ukraine before and during the conflict. We analyzed HIV-1 subtype-A pol nucleotide sequences sampled during 2012-2015 from 427 patients of 24 regional AIDS centers and used phylogeographic analysis to reconstruct virus movement among different locations in Ukraine. We then tested for correlations between reported PWID behaviors and reconstructed patterns of virus spread. Our analyses suggest that Donetsk and Lugansk, two cities not controlled by the Ukrainian government in eastern Ukraine, were significant exporters of the virus to the rest of the country. Additional analyses showed that viral dissemination within the country changed after 2013. Spearman correlation analysis showed that incoming virus flow was correlated with the number of HIV-infected internally displaced people. Additionally, there was a correlation between more intensive virus movement and locations with a higher proportion of PWID practicing risky sexual behaviors. Our findings suggest that effective prevention responses should involve internally displaced people and people who frequently travel to war-affected regions. Scale-up of harm reduction services for PWID will be an important factor in preventing new local HIV outbreaks in Ukraine.}, } @article {pmid29339467, year = {2018}, author = {Ravindran, S}, title = {Profile of Scott W. Lowe.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {630-632}, pmid = {29339467}, issn = {1091-6490}, mesh = {Genes, Neoplasm ; Genes, p53 ; Genetics/*history ; History, 20th Century ; History, 21st Century ; Humans ; Medical Oncology/*history/methods ; Oncogenes ; }, } @article {pmid29339095, year = {2018}, author = {Thompson, CA and DeLaForest, A and Battle, MA}, title = {Patterning the gastrointestinal epithelium to confer regional-specific functions.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {97-108}, doi = {10.1016/j.ydbio.2018.01.006}, pmid = {29339095}, issn = {1095-564X}, support = {R01 DK087873/DK/NIDDK NIH HHS/United States ; R01 DK111822/DK/NIDDK NIH HHS/United States ; R56 DK087873/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation ; Epithelial Cells/*cytology/physiology ; Gastrointestinal Tract/*cytology/embryology/physiology ; Gene Expression Regulation, Developmental ; Homeodomain Proteins/physiology ; Humans ; Intestinal Absorption ; Intestinal Mucosa/*cytology ; Intestine, Small/cytology ; Intracellular Signaling Peptides and Proteins/physiology ; Mice ; Morphogenesis ; Multigene Family ; Organ Specificity ; Signal Transduction/physiology ; Stomach/cytology ; Transcription Factors/physiology ; }, abstract = {The gastrointestinal (GI) tract, in simplest terms, can be described as an epithelial-lined muscular tube extending along the cephalocaudal axis from the oral cavity to the anus. Although the general architecture of the GI tract organs is conserved from end to end, the presence of different epithelial tissue structures and unique epithelial cell types within each organ enables each to perform the distinct digestive functions required for efficient nutrient assimilation. Spatiotemporal regulation of signaling pathways and downstream transcription factors controls GI epithelial morphogenesis during development to confer essential regional-specific epithelial structures and functions. Here, we discuss the fundamental functions of each GI tract organ and summarize the diversity of epithelial structures present along the cephalocaudal axis of the GI tract. Next, we discuss findings, primarily from genetic mouse models, that have defined the roles of key transcription factors during epithelial morphogenesis, including p63, SOX2, SOX15, GATA4, GATA6, HNF4A, and HNF4G. Additionally, we examine how the Hedgehog, WNT, and BMP signaling pathways contribute to defining unique epithelial features along the cephalocaudal axis of the GI tract. Lastly, we examine the molecular mechanisms controlling regionalized cytodifferentiation of organ-specific epithelial cell types within the GI tract, concentrating on the stomach and small intestine. The delineation of GI epithelial patterning mechanisms in mice has provided fundamental knowledge to guide the development and refinement of three-dimensional GI organotypic culture models such as those derived from directed differentiation of human pluripotent stem cells and those derived directly from human tissue samples. Continued examination of these pathways will undoubtedly provide vital insights into the mechanisms of GI development and disease and may afford new avenues for innovative tissue engineering and personalized medicine approaches to treating GI diseases.}, } @article {pmid29339033, year = {2018}, author = {Schwartz, C and Hams, E and Fallon, PG}, title = {Helminth Modulation of Lung Inflammation.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {388-403}, doi = {10.1016/j.pt.2017.12.007}, pmid = {29339033}, issn = {1471-5007}, support = {092530/Z/10/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Disease Susceptibility/*parasitology ; Helminthiasis/*complications/immunology ; Helminths/*immunology ; Host-Parasite Interactions/*immunology ; Humans ; Pneumonia/*complications ; }, abstract = {Parasitic helminths must establish chronic infections to complete their life cycle and therefore are potent modulators of multiple facets of host physiology. Parasitic helminths have coevolved with humans to become arguably master selectors of our immune system, whereby they have impacted on the selection of genes with beneficial mutations for both host and parasite. While helminth infections of humans are a significant health burden, studies have shown that helminths or helminth products can alter susceptibility to unrelated infectious or inflammatory diseases. This has generated interest in the use of helminth infections or molecules as therapeutics. In this review, we focus on the impact of helminth infections on pulmonary immunity, especially with regard to homeostatic lung function, pulmonary viral and bacterial (co)infections, and asthma.}, } @article {pmid29338887, year = {2018}, author = {Kret, ME and Straffon, LM}, title = {Reply to Crivelli et al.: The different faces of fear and threat. Evolutionary and cultural insights.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {193-197}, doi = {10.1016/j.jhevol.2017.11.006}, pmid = {29338887}, issn = {1095-8606}, } @article {pmid29338875, year = {2018}, author = {Gao, Y and Zhao, F}, title = {Computational Strategies for Exploring Circular RNAs.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {389-400}, doi = {10.1016/j.tig.2017.12.016}, pmid = {29338875}, issn = {0168-9525}, mesh = {Computational Biology/trends ; MicroRNAs/*genetics ; RNA/*genetics ; Sequence Analysis, RNA ; Transcriptome/*genetics ; }, abstract = {Recent studies have demonstrated that circular RNAs (circRNAs) are ubiquitous and have diverse functions and mechanisms of biogenesis. In these studies, computational profiling of circRNAs has been prevalently used as an indispensable method to provide high-throughput approaches to detect and analyze circRNAs. However, without an overall understanding of the underlying strategies, these computational methods may not be appropriately selected or used for a specific research purpose, and some misconceptions may result in biases in the analyses. In this review we attempt to illustrate the key steps and summarize tradeoff of different strategies, covering all popular algorithms for circRNA detection and various downstream analyses. We also clarify some common misconceptions and put emphasis on the fields of application for these computational methods.}, } @article {pmid29338790, year = {2018}, author = {Premakumar, Y and Griffin, MF and Szarko, M}, title = {Morphometric characterisation of human tracheas: focus on cartilaginous ring variation.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {32}, pmid = {29338790}, issn = {1756-0500}, support = {GN2339//Medical Research Council/United Kingdom ; gn2339//Action Medical Research/ ; }, mesh = {Aged ; Aged, 80 and over ; Biomechanical Phenomena ; Cadaver ; Cartilage/*anatomy & histology/physiology ; Female ; Humans ; Male ; *Models, Anatomic ; Prostheses and Implants ; Trachea/*anatomy & histology/physiology ; }, abstract = {PURPOSE: Details regarding tracheal anatomy are currently lacking, with existing literature focussing mainly on the cricoid-tracheal region or the carina. External gross anatomy and internal morphology throughout the entire trachea is important for normal physiological functioning and various clinical applications such as designs for tracheal implants or endotracheal devices.

OBJECTIVE: To determine quantitative and qualitative characteristics of gross tracheal and individual tracheal ring anatomy.

METHOD: 10 tracheas were harvested from formaldehyde-fixed cadavers. Tracheal length, height and inter-ring distance were measured from complete tracheas. Individual rings were excised and the following measurements were taken at three points on the ring: thickness, width, and antero-posterior (A-P) length.

RESULTS: The average tracheal length was 10.38 ± 0.85 cm with a mean of 19 ± 3 rings per trachea. The average width and A-P diameter of tracheal lumens were 17.31 ± 2.57 and 17.27 ± 2.56 mm, with a width-AP ratio of 1.00 ('C' shaped ring). The A-P diameter shows a trend of narrowing slightly from the upper 1/3 to the lower 1/3 of the trachea. While majority of tracheal rings consisted of the expected 'C' shape, more than 41% of the 147 counted rings consisted of abnormally shaped rings which were further analysed.

CONCLUSION: This study provides further details regarding tracheal anatomy which will be useful for implant design. Of interest for anatomists, is the marked variability in tracheal ring morphology which could be further characterised in larger studies.}, } @article {pmid29338781, year = {2018}, author = {Yamada, K and Asai, K and Okamoto, A and Watanabe, T and Kanazawa, H and Ohata, M and Ohsawa, M and Hirata, K}, title = {Correlation between disease activity and serum ferritin in clinically amyopathic dermatomyositis with rapidly-progressive interstitial lung disease: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {34}, pmid = {29338781}, issn = {1756-0500}, mesh = {Anti-Inflammatory Agents/therapeutic use ; Cyclophosphamide/therapeutic use ; Dermatomyositis/complications/drug therapy/*pathology ; Disease Progression ; Drug Therapy, Combination ; Fatal Outcome ; Ferritins/*blood ; Humans ; Immunosuppressive Agents/therapeutic use ; Lung Diseases, Interstitial/complications/drug therapy/*pathology ; Male ; Methylprednisolone/therapeutic use ; Middle Aged ; Severity of Illness Index ; Tacrolimus/therapeutic use ; }, abstract = {BACKGROUND: Clinically amyopathic dermatomyositis with anti-Melanoma Differentiation-Associated gene 5 (MDA5) antibody often presents with severe interstitial lung disease. Although serum ferritin level is known to reflect interstitial lung disease activity, there are few case reports describing this association.

CASE PRESENTATION: A 58-year-old man was referred to our outpatient clinic with a 3-week history of cough and respiratory distress. He had erythema over the V area of the neck and a Gottron's sign. Chest computed tomography revealed diffuse ground-glass opacities and reticular shadows in both lungs. Test for anti-MDA5 antibody was positive. After admission, he received triple combination therapy (methylprednisolone pulse therapy, tacrolimus, and cyclophosphamide). However, his respiratory condition worsened as the serum ferritin level increased. Despite no apparent deterioration on chest radiography, he ultimately died due to respiratory failure.

CONCLUSIONS: In this case, triple combination therapy was not effective for the patient's respiratory condition. The serum ferritin level was correlated with disease activity and was more useful than chest radiography for monitoring clinical status.}, } @article {pmid29338778, year = {2018}, author = {Carr, ZJ and Van De Louw, A and Fehr, G and Li, JD and Kunselman, A and Ruiz-Velasco, V}, title = {Increased whole blood FFA2/GPR43 receptor expression is associated with increased 30-day survival in patients with sepsis.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {41}, pmid = {29338778}, issn = {1756-0500}, support = {Study 5927//Penn State Milton S. Hershey Medical Center, Department of Anesthesiology & Perioperative Medicine/ ; }, mesh = {Adult ; Aged ; Female ; *Gene Expression ; Humans ; *Intensive Care Units ; Linear Models ; Logistic Models ; Male ; Middle Aged ; Receptors, Cell Surface/blood/*genetics ; Retrospective Studies ; Sepsis/blood/*genetics/mortality ; Survival Analysis ; Survival Rate ; Time Factors ; }, abstract = {OBJECTIVE: Sepsis is a condition associated with a dysregulated inflammatory response to infection with significant morbidity. Recent advances have elucidated the vital role that the short chain fatty acid glycoprotein receptor 43 (FFA2/GPR43) plays in inflammatory and immunomodulatory pathways. We hypothesized that elevated whole blood GPR43 RNA expression would be associated with increased 30-day survival in patients admitted with sepsis. Patients (n = 93) admitted to the intensive care unit with the diagnosis of sepsis underwent quantitative real time PCR within 48 h of intensive care unit admission. Clinical and demographical parameters were retrospectively extracted from the chart and compared to quantitative measurements of GPR43 RNA expression.

RESULTS: Utilizing logistic regression, we found that the odds of mortality decreased for every one-unit increase in GPR43 RNA expression for patients that survived to 30 days [OR = 0.71; 95% CI (0.50, 0.99) p = 0.049]. Using linear regression, we determined that the increase in whole blood GPR43 expression was not associated with whole blood white cell count [r = 0.04; 95% CI (-0.16, 0.24); p = 0.70] or body mass index [r = - 0.07; 95% CI (- 0.23, 0.18); p = 0.81]. We conclude that the GPR43 receptor plays an integral role in survival during and after sepsis.}, } @article {pmid29338777, year = {2018}, author = {Ali, SM and Anjum, N and Kamel Boulos, MN and Ishaq, M and Aamir, J and Haider, GR}, title = {Measuring management's perspective of data quality in Pakistan's Tuberculosis control programme: a test-based approach to identify data quality dimensions.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {40}, pmid = {29338777}, issn = {1756-0500}, mesh = {*Data Accuracy ; Delivery of Health Care/methods/standards/statistics & numerical data ; Humans ; Pakistan ; Program Evaluation/methods/standards/*statistics & numerical data ; Public Health/methods/standards/statistics & numerical data ; Quality Control ; Quality Improvement/standards/*statistics & numerical data ; Tuberculosis/*prevention & control ; }, abstract = {BACKGROUND: Data quality is core theme of programme's performance assessment and many organizations do not have any data quality improvement strategy, wherein data quality dimensions and data quality assessment framework are important constituents. As there is limited published research about the data quality specifics that are relevant to the context of Pakistan's Tuberculosis control programme, this study aims at identifying the applicable data quality dimensions by using the 'fitness-for-purpose' perspective.

RESULTS: Forty-two respondents pooled a total of 473 years of professional experience, out of which 223 years (47%) were in TB control related programmes. Based on the responses against 11 practical cases, adopted from the routine recording and reporting system of Pakistan's TB control programme (real identities of patient were masked), completeness, accuracy, consistency, vagueness, uniqueness and timeliness are the applicable data quality dimensions relevant to the programme's context, i.e. work settings and field of practice.

CONCLUSION: Based on a 'fitness-for-purpose' approach to data quality, this study used a test-based approach to measure management's perspective and identified data quality dimensions pertinent to the programme and country specific requirements. Implementation of a data quality improvement strategy and achieving enhanced data quality would greatly help organizations in promoting data use for informed decision making.}, } @article {pmid29338774, year = {2018}, author = {Góis, C and Duarte, TA and Paulino, S and Raposo, JF and do Carmo, I and Barbosa, A}, title = {Depressive symptoms are associated with poor glycemic control among women with type 2 diabetes mellitus.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {38}, pmid = {29338774}, issn = {1756-0500}, mesh = {Comorbidity ; Depressive Disorder/*epidemiology/psychology ; Diabetes Mellitus, Type 2/blood/*epidemiology ; Female ; Glycated Hemoglobin A/analysis ; Humans ; Hyperglycemia/blood/*epidemiology ; Linear Models ; Male ; Middle Aged ; Outpatients/*statistics & numerical data ; Portugal/epidemiology ; Sex Factors ; Surveys and Questionnaires ; }, abstract = {OBJECTIVE: In patients with type 2 diabetes mellitus, depressive symptoms may be associated with metabolic deterioration. The impact of sex on this association is unclear. The aim of this study is to analyze the relationship between depression and metabolic control by sex. The data presented is the side product of the clinical investigation by Rui Duarte, MD, Treatment Response in Type 2 Diabetes Patients with Major Depression from 2007.

RESULTS: A sample of 628 outpatients with type 2 diabetes mellitus was taken from a specialized diabetes outpatient clinic. In a univariate analysis: women's glycohemoglobin mean levels were 8.99% whereas men's were 8.41% and the difference was statistically significant. The proportion of women (34.3%) with pathological levels of depression (Hospital Anxiety Depression Scale score ≥ 8) was significantly higher than men's (15.2%). A linear regression analysis performed by sex and controlling for demographic, clinical and psychological variables, showed poorer metabolic control in women with depressive symptoms. No association was observed in men. These results support depression as a predictor for poor metabolic control in women and the need for detecting depressive symptoms when glycemic levels deteriorate.}, } @article {pmid29338770, year = {2018}, author = {Cheng, T and Small, W and Nosova, E and Hogg, B and Hayashi, K and Kerr, T and DeBeck, K}, title = {Nonmedical prescription opioid use and illegal drug use: initiation trajectory and related risks among people who use illegal drugs in Vancouver, Canada.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {35}, pmid = {29338770}, issn = {1756-0500}, support = {U01 DA038886/DA/NIDA NIH HHS/United States ; U01DA038886//Foundation for the National Institutes of Health/ ; MOP-286532//Canadian Institutes of Health Research (CA)/ ; }, mesh = {Adolescent ; Adult ; Analgesics, Opioid/*administration & dosage ; Canada/epidemiology ; Cohort Studies ; Cross-Sectional Studies ; Female ; Homeless Youth/statistics & numerical data ; Humans ; Male ; Middle Aged ; Prescription Drug Misuse/*statistics & numerical data ; Prevalence ; Risk Factors ; Street Drugs/*poisoning ; Substance-Related Disorders/*epidemiology/etiology ; }, abstract = {OBJECTIVE: We investigated the prevalence of and risk factors associated with initiating nonmedical prescription opioid use (NMPOU) before and after illegal drugs using data from two linked cohort studies of street youth and adults who use illegal drugs in Vancouver, Canada. All participants who attended a study visit between 2013 and 2016 were eligible for the primary analyses.

RESULTS: Among 512 youth and 833 adult participants, the prevalence of NMPOU was extremely high (88% among street youth; 90% among adults), and over one-third of those who reported engaging in NMPOU had initiated NMPOU before illegal drug use (vs. transitioning from illegal drugs to NMPOU). Participants who reported either transitioning to or from NMPOU had higher risk profiles, particularly related to substance use, when compared with those who reported never engaging in NMPOU. Sub-analyses restricted to only those who engaged in NMPOU found few statistically significant differences between those who initiated NMPOU prior to illegal drugs versus those who initiated illegal drugs prior to NMPOU. Findings suggest that among people who use illegal drugs, early NMPOU trajectories do not appear to critically shape future patterns and practices.}, } @article {pmid29338769, year = {2018}, author = {Komagamine, J and Kobayashi, M}, title = {Publication rate of abstracts presented at Japan Geriatrics Society Annual Meetings (2011-2012): a retrospective observational study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {36}, pmid = {29338769}, issn = {1756-0500}, abstract = {OBJECTIVE: We aimed to determine the publication rate of abstracts presented at Japan Geriatrics Society Annual Meetings. Publication rates were determined by searching for full-text publications up to September 2017 in the MEDLINE database. Factors associated with publication were determined.

RESULTS: In total, 618 abstracts presented at Japan Geriatrics Society Annual Meetings (2011-2012) were included. Of those, 146 (23.6% [95% CI 20.3-27.0%]) were published in peer-reviewed journals indexed in MEDLINE. The median time to publication was 13.0 months (interquartile range 6.0-25.8 months). More than 90% were published within 4 years. The publications appeared in 64 different journals, and 87.0% were published in English-language journals. Multivariable analysis revealed more frequent publication of oral presentations (25.4% vs 16.9% of poster presentations; adjusted OR 1.79 [95% CI 1.05-3.06]), randomized controlled trials (66.7% vs 22.8% for other study designs; adjusted OR 10.79 [95% CI 3.02-38.53]) and studies with n ≥ 100 (28.7% vs 18.4% of studies with n < 100; adjusted OR 1.97 [95% CI 1.32-2.95]). Because more than three-fourths of the abstracts presented at Japan Geriatrics Society Annual Meetings remained unpublished within 5 years after the conferences, additional efforts may be needed to promote their publication.}, } @article {pmid29338766, year = {2018}, author = {Cui, H and Zheng, M and Zhao, G and Liu, R and Wen, J}, title = {Identification of differentially expressed genes and pathways for intramuscular fat metabolism between breast and thigh tissues of chickens.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {55}, pmid = {29338766}, issn = {1471-2164}, support = {31372305//National Natural Science Foundation of China/International ; }, mesh = {Adipose Tissue/*metabolism ; Animals ; Chickens/genetics/*metabolism ; Female ; Gene Expression Profiling ; Mammary Glands, Animal/*metabolism ; Muscles ; Oligonucleotide Array Sequence Analysis ; Signal Transduction ; Thigh ; }, abstract = {BACKGROUND: Intramuscular fat (IMF) is one of the important factors influencing meat quality, however, for chickens, the molecular regulatory mechanisms underlying this trait have not yet been clear. In this study, a systematic identification of differentially expressed genes (DEGs) and molecular regulatory mechanism related to IMF metabolism between Beijing-you chicken breast and thigh at 42 and 90 days of age was performed.

RESULTS: IMF contents, Gene Ontology (GO) terms, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways were analyzed, The results showed that both IMF contents in breast at 42 and 90 d were significantly lower (P < 0.05 or P < 0.01) than those in thigh. By microarray, 515 common known DEGs and 36 DEGs related to IMF metabolism were identified between the breast and thigh at 42 and 90 d. Compared to thigh, the expression levels of PPARG had significantly down-regulated (P < 0.01) in breast, but the expression levels of RXRA and CEBPB had significantly up-regulated (P < 0.01). However, the expression levels of LPL, FABP4, THRSP, RBP7, LDLR, FABP3, CPT2 and PPARGC1A had significantly down-regulated in breast (P < 0.01), supporting that PPARG and its down-stream genes had the important regulatory function to IMF deposition. In addition, based on of DEGs, KEGG analysis revealed that PPAR signaling pathway and cell junction-related pathways (focal adhesion and ECM-receptor interaction, which play a prominent role in maintaining the integrity of tissues), might contribute to the IMF metabolism in chicken.

CONCLUSIONS: Our data had screened the potential candidate genes associated with chicken IMF metabolism, and imply that IMF metabolism in chicken is regulated and mediated not only by related functional genes and PPAR pathway, but also by others involved in cell junctions. These findings establish the groundwork and provide new clues for deciphering the molecular mechanisms underlying IMF deposition in poultry. Further studies at the translational and posttranslational level are now required to validate the genes and pathways identified here.}, } @article {pmid29338765, year = {2018}, author = {Ndongo, R and Tolefac, PN and Tambo, FFM and Abanda, MH and Ngowe, MN and Fola, O and Dzekem, B and Weledji, PE and Sosso, MA and Minkande, JZ}, title = {Infantile hypertrophic pyloric stenosis: a 4-year experience from two tertiary care centres in Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {33}, pmid = {29338765}, issn = {1756-0500}, mesh = {Cameroon ; Female ; Humans ; Infant ; Infant, Newborn ; Length of Stay/statistics & numerical data ; Logistic Models ; Male ; Nausea/etiology ; Postoperative Complications/etiology ; Pyloric Stenosis, Hypertrophic/diagnosis/*surgery ; Pyloromyotomy/adverse effects/*methods ; *Tertiary Care Centers ; Vomiting/etiology ; }, abstract = {OBJECTIVE: This study aimed to describe the clinical characteristics of patients with infantile hypertrophic stenosis, management and its outcome in two tertiary care centres in Cameroon.

RESULTS: A total of 21 patients were included from the two centres. The mean age at presentation was 5.2 ± 1.2 weeks, predominantly male with a male-to-female ratio of 4.25:1. The triad of vomiting, visible peristalsis and palpable mass was present in only 7 (33.3%) of the participants. The diagnosis was confirmed with ultrasounds in all participants. Ramstedt pyloromyotomy was done in all participants and in 9.5% of the participants it was complicated by intra-operative duodenal perforation whereas in the postoperative period the most common complications were vomiting (6, 28.6%), sepsis (2, 9.5%), and paralytic ileus (2, 9.5%). The mortality rate from the series is 9.5%. According to univariate logistic regression: severe dehydration [OR = 5.41, 95% CI = (3.11-6.97), p = 0.002], hypokalaemia [OR = 2.63, 95% CI = (1.02-5.91), p = 0.042] and surgical site infection [OR = 3.12, 95% CI (1.22-5.64), p = 0.023] were the main predictors of mortality whereas postoperative hospital length of stay > 5 days was significantly associated with surgical site infection [OR = 2.44, 95% CI = (1.12-6.44), p = 0.002] and postoperative nausea and vomiting [OR = 3.64, 95% CI = (1.18-6.64), p = 0.022].}, } @article {pmid29338764, year = {2018}, author = {Hartman, K and van der Heijden, MGA and Wittwer, RA and Banerjee, S and Walser, JC and Schlaeppi, K}, title = {Cropping practices manipulate abundance patterns of root and soil microbiome members paving the way to smart farming.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {14}, pmid = {29338764}, issn = {2049-2618}, support = {PDFMP3_137136//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; 31003A_165891//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; }, mesh = {Bacteria/*classification/genetics/isolation & purification ; Crop Production/*methods ; Fungi/*classification/genetics/isolation & purification ; Microbiota ; Phylogeny ; Plant Roots/microbiology ; *Soil Microbiology ; Triticum/*microbiology ; }, abstract = {BACKGROUND: Harnessing beneficial microbes presents a promising strategy to optimize plant growth and agricultural sustainability. Little is known to which extent and how specifically soil and plant microbiomes can be manipulated through different cropping practices. Here, we investigated soil and wheat root microbial communities in a cropping system experiment consisting of conventional and organic managements, both with different tillage intensities.

RESULTS: While microbial richness was marginally affected, we found pronounced cropping effects on community composition, which were specific for the respective microbiomes. Soil bacterial communities were primarily structured by tillage, whereas soil fungal communities responded mainly to management type with additional effects by tillage. In roots, management type was also the driving factor for bacteria but not for fungi, which were generally determined by changes in tillage intensity. To quantify an "effect size" for microbiota manipulation, we found that about 10% of variation in microbial communities was explained by the tested cropping practices. Cropping sensitive microbes were taxonomically diverse, and they responded in guilds of taxa to the specific practices. These microbes also included frequent community members or members co-occurring with many other microbes in the community, suggesting that cropping practices may allow manipulation of influential community members.

CONCLUSIONS: Understanding the abundance patterns of cropping sensitive microbes presents the basis towards developing microbiota management strategies for smart farming. For future targeted microbiota management-e.g., to foster certain microbes with specific agricultural practices-a next step will be to identify the functional traits of the cropping sensitive microbes.}, } @article {pmid29338763, year = {2018}, author = {Molu, JP and Essome, MCN and Monamele, CG and Njouom, R}, title = {Sero-prevalence of HBsAg in naive HIV-infected patients in a rural locality of Cameroon.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {39}, pmid = {29338763}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Cameroon/epidemiology ; Child ; Child, Preschool ; Coinfection/blood/epidemiology/virology ; Cross-Sectional Studies ; Female ; HIV Infections/*blood/epidemiology/virology ; Hepatitis B/*blood/epidemiology/virology ; Hepatitis B Surface Antigens/*blood ; Hepatitis B virus/*immunology/physiology ; Humans ; Male ; Middle Aged ; Prevalence ; Retrospective Studies ; Rural Population/*statistics & numerical data ; Seroepidemiologic Studies ; Young Adult ; }, abstract = {OBJECTIVE: This study was performed in order to fill the gap of knowledge regarding sero-epidemiology of hepatitis B virus (HBV) amongst Human Immunodeficiency virus (HIV)-infected patients and to assess the risk factors associated with HBV co-infection in a rural locality of Cameroon. A retrospective and cross-sectional study was carried out from January 2008 to April 2014 within the Mfou District Hospital. Naive HIV-infected patients were enrolled in the study and tested for hepatitis B surface antigen (HBsAg). Preliminary pre-therapeutic data essential for follow-up was collected from the participants.

RESULTS: Overall, the sample size was constituted of 712 HIV-infected patients. The prevalence of HBsAg was 8.99%. A significant difference was observed in the proportion of HBsAg positive subjects with respect to the year of inclusion; higher proportions were observed between 2011 and 2014 (P-value = 0.007). Majority of HBV co-infected participants had severe immuno-suppression with CD4 counts lower than 100 cells/µL as compared to HIV mono-infected population but the difference was not statistically significant. Our results confirm the high prevalence for HBV infection among HIV-infected patients in the Mfou District Hospital. These findings will enable stake holders to be better armed in the elimination of viral hepatitis as a public health problem.}, } @article {pmid29338757, year = {2018}, author = {Mitchenall, LA and Hipkin, RE and Piperakis, MM and Burton, NP and Maxwell, A}, title = {A rapid high-resolution method for resolving DNA topoisomers.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {37}, pmid = {29338757}, issn = {1756-0500}, support = {BBS/E/J/00000201//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004561/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {DNA/*analysis/genetics ; DNA Gyrase/metabolism ; DNA Topoisomerases/metabolism ; DNA, Superhelical/*analysis/genetics/metabolism ; Electrophoresis, Agar Gel/*methods ; Electrophoresis, Capillary/*methods ; Plasmids/genetics ; Reproducibility of Results ; }, abstract = {OBJECTIVE: Agarose gel electrophoresis has been the mainstay technique for the analysis of DNA samples of moderate size. In addition to separating linear DNA molecules, it can also resolve different topological forms of plasmid DNAs, an application useful for the analysis of the reactions of DNA topoisomerases. However, gel electrophoresis is an intrinsically low-throughput technique and suffers from other potential disadvantages. We describe the application of the QIAxcel Advanced System, a high-throughput capillary electrophoresis system, to separate DNA topoisomers, and compare this technique with gel electrophoresis.

RESULTS: We prepared a range of topoisomers of plasmids pBR322 and pUC19, and a 339 bp DNA minicircle, and compared their separation by gel electrophoresis and the QIAxcel System. We found superior resolution with the QIAxcel System, and that quantitative analysis of topoisomer distributions was straightforward. We show that the QIAxcel system has advantages in terms of speed, resolution and cost, and can be applied to DNA circles of various sizes. It can readily be adapted for use in compound screening against topoisomerase targets.}, } @article {pmid29338718, year = {2018}, author = {Ballister, ER and Rodgers, J and Martial, F and Lucas, RJ}, title = {A live cell assay of GPCR coupling allows identification of optogenetic tools for controlling Go and Gi signaling.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {10}, pmid = {29338718}, issn = {1741-7007}, support = {//Wellcome Trust/United Kingdom ; BB/K002252/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Animal opsins are light-sensitive G-protein-coupled receptors (GPCRs) that enable optogenetic control over the major heterotrimeric G-protein signaling pathways in animal cells. As such, opsins have potential applications in both biomedical research and therapy. Selecting the opsin with the best balance of activity and selectivity for a given application requires knowing their ability to couple to a full range of relevant Gα subunits. We present the GsX assay, a set of tools based on chimeric Gs subunits that transduce coupling of opsins to diverse G proteins into increases in cAMP levels, measured with a real-time reporter in living cells. We use this assay to compare coupling to Gi/o/t across a panel of natural and chimeric opsins selected for potential application in gene therapy for retinal degeneration.

RESULTS: Of the opsins tested, wild-type human rod opsin had the highest activity for chimeric Gs proxies for Gi and Gt (Gsi and Gst) and was matched in Go proxy (Gso) activity only by a human rod opsin/scallop opsin chimera. Rod opsin drove roughly equivalent responses via Gsi, Gso, and Gst, while cone opsins showed much lower activities with Gso than Gsi or Gst, and a human rod opsin/amphioxus opsin chimera demonstrated higher activity with Gso than with Gsi or Gst. We failed to detect activity for opsin chimeras bearing three intracellular fragments of mGluR6, and observed unexpectedly complex response profiles for scallop and amphioxus opsins thought to be specialized for Go.

CONCLUSIONS: These results identify rod opsin as the most potent non-selective Gi/o/t-coupled opsin, long-wave sensitive cone opsin as the best for selectively activating Gi/t over Go, and a rod opsin/amphioxus opsin chimera as the best choice for selectively activating Go over Gi/t.}, } @article {pmid29338715, year = {2018}, author = {Ramos, B and González-Acuña, D and Loyola, DE and Johnson, WE and Parker, PG and Massaro, M and Dantas, GPM and Miranda, MD and Vianna, JA}, title = {Landscape genomics: natural selection drives the evolution of mitogenome in penguins.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {53}, pmid = {29338715}, issn = {1471-2164}, support = {11110060 and 1150517//Fondo Nacional de Desarrollo Científico y Tecnológico (CL)/International ; INACH T12-13//Instituto Antártico Chileno/International ; DI-410-13/I//Universidad Andres Bello/International ; 482501/2013-8 and 490403/2008-5//Conselho Nacional de Desenvolvimento Científico e Tecnológico (BR)/International ; 2009/08624//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; ANT 0944411//Directorate for Biological Sciences/International ; C01X1001//Ministry of Science and Innovation, New Zealand/International ; }, mesh = {Animals ; DNA, Mitochondrial/chemistry ; *Evolution, Molecular ; Gene-Environment Interaction ; *Genome, Mitochondrial ; Genomics ; *Selection, Genetic ; Spheniscidae/*genetics ; }, abstract = {BACKGROUND: Mitochondria play a key role in the balance of energy and heat production, and therefore the mitochondrial genome is under natural selection by environmental temperature and food availability, since starvation can generate more efficient coupling of energy production. However, selection over mitochondrial DNA (mtDNA) genes has usually been evaluated at the population level. We sequenced by NGS 12 mitogenomes and with four published genomes, assessed genetic variation in ten penguin species distributed from the equator to Antarctica. Signatures of selection of 13 mitochondrial protein-coding genes were evaluated by comparing among species within and among genera (Spheniscus, Pygoscelis, Eudyptula, Eudyptes and Aptenodytes). The genetic data were correlated with environmental data obtained through remote sensing (sea surface temperature [SST], chlorophyll levels [Chl] and a combination of SST and Chl [COM]) through the distribution of these species.

RESULTS: We identified the complete mtDNA genomes of several penguin species, including ND6 and 8 tRNAs on the light strand and 12 protein coding genes, 14 tRNAs and two rRNAs positioned on the heavy strand. The highest diversity was found in NADH dehydrogenase genes and the lowest in COX genes. The lowest evolutionary divergence among species was between Humboldt (Spheniscus humboldti) and Galapagos (S. mendiculus) penguins (0.004), while the highest was observed between little penguin (Eudyptula minor) and Adélie penguin (Pygoscelis adeliae) (0.097). We identified a signature of purifying selection (Ka/Ks < 1) across the mitochondrial genome, which is consistent with the hypothesis that purifying selection is constraining mitogenome evolution to maintain Oxidative phosphorylation (OXPHOS) proteins and functionality. Pairwise species maximum-likelihood analyses of selection at codon sites suggest positive selection has occurred on ATP8 (Fixed-Effects Likelihood, FEL) and ND4 (Single Likelihood Ancestral Counting, SLAC) in all penguins. In contrast, COX1 had a signature of strong negative selection. ND4 Ka/Ks ratios were highly correlated with SST (Mantel, p-value: 0.0001; GLM, p-value: 0.00001) and thus may be related to climate adaptation throughout penguin speciation.

CONCLUSIONS: These results identify mtDNA candidate genes under selection which could be involved in broad-scale adaptations of penguins to their environment. Such knowledge may be particularly useful for developing predictive models of how these species may respond to severe climatic changes in the future.}, } @article {pmid29338710, year = {2018}, author = {Shen, Y and Dana, H and Abdelfattah, AS and Patel, R and Shea, J and Molina, RS and Rawal, B and Rancic, V and Chang, YF and Wu, L and Chen, Y and Qian, Y and Wiens, MD and Hambleton, N and Ballanyi, K and Hughes, TE and Drobizhev, M and Kim, DS and Koyama, M and Schreiter, ER and Campbell, RE}, title = {A genetically encoded Ca2+ indicator based on circularly permutated sea anemone red fluorescent protein eqFP578.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {9}, pmid = {29338710}, issn = {1741-7007}, support = {U01 NS094246/NS/NINDS NIH HHS/United States ; U01 NS094246/NH/NIH HHS/United States ; U01 NS090565/NS/NINDS NIH HHS/United States ; MOP-123514//CIHR/Canada ; }, abstract = {BACKGROUND: Genetically encoded calcium ion (Ca2+) indicators (GECIs) are indispensable tools for measuring Ca2+ dynamics and neuronal activities in vitro and in vivo. Red fluorescent protein (RFP)-based GECIs have inherent advantages relative to green fluorescent protein-based GECIs due to the longer wavelength light used for excitation. Longer wavelength light is associated with decreased phototoxicity and deeper penetration through tissue. Red GECI can also enable multicolor visualization with blue- or cyan-excitable fluorophores.

RESULTS: Here we report the development, structure, and validation of a new RFP-based GECI, K-GECO1, based on a circularly permutated RFP derived from the sea anemone Entacmaea quadricolor. We have characterized the performance of K-GECO1 in cultured HeLa cells, dissociated neurons, stem-cell-derived cardiomyocytes, organotypic brain slices, zebrafish spinal cord in vivo, and mouse brain in vivo.

CONCLUSION: K-GECO1 is the archetype of a new lineage of GECIs based on the RFP eqFP578 scaffold. It offers high sensitivity and fast kinetics, similar or better than those of current state-of-the-art indicators, with diminished lysosomal accumulation and minimal blue-light photoactivation. Further refinements of the K-GECO1 lineage could lead to further improved variants with overall performance that exceeds that of the most highly optimized red GECIs.}, } @article {pmid29338709, year = {2018}, author = {Hakim, A and Mor, Y and Toker, IA and Levine, A and Neuhof, M and Markovitz, Y and Rechavi, O}, title = {WorMachine: machine learning-based phenotypic analysis tool for worms.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {8}, pmid = {29338709}, issn = {1741-7007}, support = {P40 OD010440/OD/NIH HHS/United States ; }, abstract = {BACKGROUND: Caenorhabditis elegans nematodes are powerful model organisms, yet quantification of visible phenotypes is still often labor-intensive, biased, and error-prone. We developed WorMachine, a three-step MATLAB-based image analysis software that allows (1) automated identification of C. elegans worms, (2) extraction of morphological features and quantification of fluorescent signals, and (3) machine learning techniques for high-level analysis.

RESULTS: We examined the power of WorMachine using five separate representative assays: supervised classification of binary-sex phenotype, scoring continuous-sexual phenotypes, quantifying the effects of two different RNA interference treatments, and measuring intracellular protein aggregation.

CONCLUSIONS: WorMachine is suitable for analysis of a variety of biological questions and provides an accurate and reproducible analysis tool for measuring diverse phenotypes. It serves as a "quick and easy," convenient, high-throughput, and automated solution for nematode research.}, } @article {pmid29338696, year = {2018}, author = {LaVoie, SP and Summers, AO}, title = {Transcriptional responses of Escherichia coli during recovery from inorganic or organic mercury exposure.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {52}, pmid = {29338696}, issn = {1471-2164}, support = {ER64408//U.S. Department of Energy/International ; ER65286//U.S. Department of Energy/International ; }, mesh = {Electron Transport/genetics ; Escherichia coli K12/*drug effects/*genetics/metabolism ; Gene Expression Regulation, Bacterial/drug effects ; Mercuric Chloride/*toxicity ; Phenylmercuric Acetate/*toxicity ; Stress, Physiological/genetics ; Transcriptome/*drug effects ; }, abstract = {BACKGROUND: The protean chemical properties of mercury have long made it attractive for diverse applications, but its toxicity requires great care in its use, disposal, and recycling. Mercury occurs in multiple chemical forms, and the molecular basis for the distinct toxicity of its various forms is only partly understood. Global transcriptomics applied over time can reveal how a cell recognizes a toxicant and what cellular subsystems it marshals to repair and recover from the damage. The longitudinal effects on the transcriptome of exponential phase E. coli were compared during sub-acute exposure to mercuric chloride (HgCl2) or to phenylmercuric acetate (PMA) using RNA-Seq.

RESULTS: Differential gene expression revealed common and distinct responses to the mercurials throughout recovery. Cultures exhibited growth stasis immediately after each mercurial exposure but returned to normal growth more quickly after PMA exposure than after HgCl2 exposure. Correspondingly, PMA rapidly elicited up-regulation of a large number of genes which continued for 30 min, whereas fewer genes were up-regulated early after HgCl2 exposure only some of which overlapped with PMA up-regulated genes. By 60 min gene expression in PMA-exposed cells was almost indistinguishable from unexposed cells, but HgCl2 exposed cells still had many differentially expressed genes. Relative expression of energy production and most metabolite uptake pathways declined with both compounds, but nearly all stress response systems were up-regulated by one or the other mercurial during recovery.

CONCLUSIONS: Sub-acute exposure influenced expression of ~45% of all genes with many distinct responses for each compound, reflecting differential biochemical damage by each mercurial and the corresponding resources available for repair. This study is the first global, high-resolution view of the transcriptional responses to any common toxicant in a prokaryotic model system from exposure to recovery of active growth. The responses provoked by these two mercurials in this model bacterium also provide insights about how higher organisms may respond to these ubiquitous metal toxicants.}, } @article {pmid29338691, year = {2018}, author = {Diaz-Del-Pino, S and Trelles, O and Falgueras, J}, title = {mORCA: ubiquitous access to life science web services.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {56}, pmid = {29338691}, issn = {1471-2164}, mesh = {*Computational Biology ; *Computers, Handheld ; Internet ; *Software ; User-Computer Interface ; Workflow ; }, abstract = {BACKGROUND: Technical advances in mobile devices such as smartphones and tablets have produced an extraordinary increase in their use around the world and have become part of our daily lives. The possibility of carrying these devices in a pocket, particularly mobile phones, has enabled ubiquitous access to Internet resources. Furthermore, in the life sciences world there has been a vast proliferation of data types and services that finish as Web Services. This suggests the need for research into mobile clients to deal with life sciences applications for effective usage and exploitation.

RESULTS: Analysing the current features in existing bioinformatics applications managing Web Services, we have devised, implemented, and deployed an easy-to-use web-based lightweight mobile client. This client is able to browse, select, compose parameters, invoke, and monitor the execution of Web Services stored in catalogues or central repositories. The client is also able to deal with huge amounts of data between external storage mounts. In addition, we also present a validation use case, which illustrates the usage of the application while executing, monitoring, and exploring the results of a registered workflow. The software its available in the Apple Store and Android Market and the source code is publicly available in Github.

CONCLUSIONS: Mobile devices are becoming increasingly important in the scientific world due to their strong potential impact on scientific applications. Bioinformatics should not fall behind this trend. We present an original software client that deals with the intrinsic limitations of such devices and propose different guidelines to provide location-independent access to computational resources in bioinformatics and biomedicine. Its modular design makes it easily expandable with the inclusion of new repositories, tools, types of visualization, etc.}, } @article {pmid29338687, year = {2018}, author = {Tagliotti, ME and Deperi, SI and Bedogni, MC and Zhang, R and Manrique Carpintero, NC and Coombs, J and Douches, D and Huarte, MA}, title = {Use of easy measurable phenotypic traits as a complementary approach to evaluate the population structure and diversity in a high heterozygous panel of tetraploid clones and cultivars.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {8}, pmid = {29338687}, issn = {1471-2156}, mesh = {Bayes Theorem ; *Breeding ; Phenotype ; Phylogeny ; Polymorphism, Single Nucleotide ; Solanum tuberosum/*genetics ; }, abstract = {BACKGROUND: Diversity in crops is fundamental for plant breeding efforts. An accurate assessment of genetic diversity, using molecular markers, such as single nucleotide polymorphism (SNP), must be able to reveal the structure of the population under study. A characterization of population structure using easy measurable phenotypic traits could be a preliminary and low-cost approach to elucidate the genetic structure of a population. A potato population of 183 genotypes was evaluated using 4859 high-quality SNPs and 19 phenotypic traits commonly recorded in potato breeding programs. A Bayesian approach, Minimum Spanning Tree (MST) and diversity estimator, as well as multivariate analysis based on phenotypic traits, were adopted to assess the population structure.

RESULTS: Analysis based on molecular markers showed groups linked to the phylogenetic relationship among the germplasm as well as the link with the breeding program that provided the material. Diversity estimators consistently structured the population according to a priori group estimation. The phenotypic traits only discriminated main groups with contrasting characteristics, as different subspecies, ploidy level or membership in a breeding program, but were not able to discriminate within groups. A joint molecular and phenotypic characterization analysis discriminated groups based on phenotypic classification, taxonomic category, provenance source of genotypes and genetic background.

CONCLUSIONS: This paper shows the significant level of diversity existing in a parental population of potato as well as the putative phylogenetic relationships among the genotypes. The use of easily measurable phenotypic traits among highly contrasting genotypes could be a reasonable approach to estimate population structure in the initial phases of a potato breeding program.}, } @article {pmid29338683, year = {2018}, author = {Acuña-Amador, L and Primot, A and Cadieu, E and Roulet, A and Barloy-Hubler, F}, title = {Genomic repeats, misassembly and reannotation: a case study with long-read resequencing of Porphyromonas gingivalis reference strains.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {54}, pmid = {29338683}, issn = {1471-2164}, mesh = {Bacteroidetes/genetics ; DNA, Bacterial/chemistry ; *Genome, Bacterial ; *Genomics/standards ; Molecular Sequence Annotation ; Porphyromonas gingivalis/*genetics ; Reference Standards ; *Repetitive Sequences, Nucleic Acid ; Whole Genome Sequencing/standards ; }, abstract = {BACKGROUND: Without knowledge of their genomic sequences, it is impossible to make functional models of the bacteria that make up human and animal microbiota. Unfortunately, the vast majority of publicly available genomes are only working drafts, an incompleteness that causes numerous problems and constitutes a major obstacle to genotypic and phenotypic interpretation. In this work, we began with an example from the class Bacteroidia in the phylum Bacteroidetes, which is preponderant among human orodigestive microbiota. We successfully identify the genetic loci responsible for assembly breaks and misassemblies and demonstrate the importance and usefulness of long-read sequencing and curated reannotation.

RESULTS: We showed that the fragmentation in Bacteroidia draft genomes assembled from massively parallel sequencing linearly correlates with genomic repeats of the same or greater size than the reads. We also demonstrated that some of these repeats, especially the long ones, correspond to misassembled loci in three reference Porphyromonas gingivalis genomes marked as circularized (thus complete or finished). We prove that even at modest coverage (30X), long-read resequencing together with PCR contiguity verification (rrn operons and an integrative and conjugative element or ICE) can be used to identify and correct the wrongly combined or assembled regions. Finally, although time-consuming and labor-intensive, consistent manual biocuration of three P. gingivalis strains allowed us to compare and correct the existing genomic annotations, resulting in a more accurate interpretation of the genomic differences among these strains.

CONCLUSIONS: In this study, we demonstrate the usefulness and importance of long-read sequencing in verifying published genomes (even when complete) and generating assemblies for new bacterial strains/species with high genomic plasticity. We also show that when combined with biological validation processes and diligent biocurated annotation, this strategy helps reduce the propagation of errors in shared databases, thus limiting false conclusions based on incomplete or misleading information.}, } @article {pmid29338682, year = {2018}, author = {Zeng, X and Liu, H and Du, H and Wang, S and Yang, W and Chi, Y and Wang, J and Huang, F and Yu, D}, title = {Soybean MADS-box gene GmAGL1 promotes flowering via the photoperiod pathway.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {51}, pmid = {29338682}, issn = {1471-2164}, support = {2016ZX08004-003;2016ZX08009003-004//Key Transgenic Breeding Program of China/International ; 31371644;31601324//National Natural Science Foundation of China/International ; JCIC-MCP//Jiangsu Collaborative Innovation Center for Modern Crop Production/International ; }, mesh = {Circadian Rhythm/genetics ; Flowers/*genetics/*growth & development ; Gene Expression Regulation, Plant ; *Genes, Plant ; *Photoperiod ; Plants, Genetically Modified/genetics/growth & development/metabolism ; Protein Biosynthesis ; Soybeans/*genetics/*growth & development/metabolism ; Transcription Factors/genetics/*metabolism/physiology ; Transcription, Genetic ; Transcriptome ; }, abstract = {BACKGROUND: The MADS-box transcription factors are an ancient family of genes that regulate numerous physiological and biochemical processes in plants and facilitate the development of floral organs. However, the functions of most of these transcription factors in soybean remain unknown.

RESULTS: In this work, a MADS-box gene, GmAGL1, was overexpressed in soybean. Phenotypic analysis showed that GmAGL1 overexpression not only resulted in early maturation but also promoted flowering and affected petal development. Furthermore, the GmAGL1 was much more effective at promoting flowering under long-day conditions than under short-day conditions. Transcriptome sequencing analysis showed that before flowering, the photoperiod pathway photoreceptor CRY2 and several circadian rhythm genes, such as SPA1, were significantly down-regulated, while some other flowering-promoting circadian genes, such as GI and LHY, and downstream genes related to flower development, such as FT, LEAFY, SEP1, SEP3, FUL, and AP1, were up-regulated compared with the control. Other genes related to the flowering pathway were not noticeably affected.

CONCLUSIONS: The findings reported herein indicate that GmAGL1 may promote flowering mainly through the photoperiod pathway. Interestingly, while overexpression of GmAGL1 promoted plant maturity, no reduction in seed production or oil and protein contents was observed.}, } @article {pmid29338681, year = {2018}, author = {Katsura, Y and Kondo, HX and Ryan, J and Harley, V and Satta, Y}, title = {The evolutionary process of mammalian sex determination genes focusing on marsupial SRYs.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {3}, pmid = {29338681}, issn = {1471-2148}, support = {24770225//Grant-in-Aid for Scientific Research of the Ministry of Education, Culture, Sports, Science and Technology of Japan/International ; 2013//Yamada Science Foundation/International ; 24-429//The Japan Science Society/International ; 24177//Japan Society for the Promotion of Science/International ; JPMJCR14M3//Core Research for Evolutional Science and Technology/International ; }, mesh = {Amino Acid Sequence ; Animals ; DNA/metabolism ; *Evolution, Molecular ; Genes, Reporter ; *Genes, sry ; Luciferases/metabolism ; Male ; Marsupialia/*genetics ; Phylogeny ; Protein Binding ; Sex Determination Processes/*genetics ; Thermodynamics ; }, abstract = {BACKGROUND: Maleness in mammals is genetically determined by the Y chromosome. On the Y chromosome SRY is known as the mammalian male-determining gene. Both placental mammals (Eutheria) and marsupial mammals (Metatheria) have SRY genes. However, only eutherian SRY genes have been empirically examined by functional analyses, and the involvement of marsupial SRY in male gonad development remains speculative.

RESULTS: In order to demonstrate that the marsupial SRY gene is similar to the eutherian SRY gene in function, we first examined the sequence differences between marsupial and eutherian SRY genes. Then, using a parsimony method, we identify 7 marsupial-specific ancestral substitutions, 13 eutherian-specific ancestral substitutions, and 4 substitutions that occurred at the stem lineage of therian SRY genes. A literature search and molecular dynamics computational simulations support that the lineage-specific ancestral substitutions might be involved with the functional differentiation between marsupial and eutherian SRY genes. To address the function of the marsupial SRY gene in male determination, we performed luciferase assays on the testis enhancer of Sox9 core (TESCO) using the marsupial SRY. The functional assay shows that marsupial SRY gene can weakly up-regulate the luciferase expression via TESCO.

CONCLUSIONS: Despite the sequence differences between the marsupial and eutherian SRY genes, our functional assay indicates that the marsupial SRY gene regulates SOX9 as a transcription factor in a similar way to the eutherian SRY gene. Our results suggest that SRY genes obtained the function of male determination in the common ancestor of Theria (placental mammals and marsupials). This suggests that the marsupial SRY gene has a function in male determination, but additional experiments are needed to be conclusive.}, } @article {pmid29337356, year = {2018}, author = {Cattelan, S and Di Nisio, A and Pilastro, A}, title = {Stabilizing selection on sperm number revealed by artificial selection and experimental evolution.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {698-706}, doi = {10.1111/evo.13425}, pmid = {29337356}, issn = {1558-5646}, abstract = {Sperm competition is taxonomically widespread in animals and is usually associated with large sperm production, being the number of sperm in the competing pool the prime predictor of fertilization success. Despite the strong postcopulatory selection acting directionally on sperm production, its genetic variance is often very high. This can be explained by trade-offs between sperm production and traits associated with mate acquisition or survival, that may contribute to generate an overall stabilizing selection. To investigate this hypothesis, we first artificially selected male guppies (Poecilia reticulata) for high and low sperm production for three generations, while simultaneously removing sexual selection. Then, we interrupted artificial selection and restored sexual selection. Sperm production responded to divergent selection in one generation, and when we restored sexual selection, both high and low lines converged back to the mean sperm production of the original population within two generations, indicating that sperm number is subject to strong stabilizing total sexual selection (i.e., selection acting simultaneously on all traits associated with reproductive success). We discuss the possible mechanisms responsible for the maintenance of high genetic variability in sperm production despite strong selection acting on it.}, } @article {pmid29337274, year = {2018}, author = {Ballesteros, JA and Hormiga, G}, title = {Species delimitation of the North American orchard-spider Leucauge venusta (Walckenaer, 1841) (Araneae, Tetragnathidae).}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {183-197}, doi = {10.1016/j.ympev.2018.01.002}, pmid = {29337274}, issn = {1095-9513}, mesh = {Animals ; Brazil ; Calibration ; Canada ; Ecosystem ; Florida ; Geography ; Male ; Mexico ; Mitochondria/genetics ; North America ; *Phylogeny ; Probability ; Species Specificity ; Spiders/classification/*genetics ; Time Factors ; United States ; }, abstract = {The orchard spider, Leucauge venusta (Walckenaer, 1841) is one of the most common and abundant orb-weavers in North America. This species has a broad geographic distribution extending across tropical and temperate regions of the Americas from Canada to Brazil. Guided by a preliminary observation of the barcode gap between sequences from specimens of L. venusta collected in Florida and other North American localities, we collected across a transect through the southeastern USA to investigate the observed genetic divide. The dataset, complemented with additional samples from Mexico, and Brazil was analyzed for species delimitation using STACEY and bGMYC based on sequences from one nuclear (ITS2) and one mitochondrial marker (COI). The analyses clearly separate USA samples into two deeply divergent and geographically structured groups (north-south) which we interpret as two different species. We generated ecological niche models for these two groups rejecting a niche equivalence hypothesis for these lineages. Taxonomic changes are proposed based on these findings, Leucauge venusta is restricted to denote the northern clade, and its known distribution restricted to the USA. Leucauge argyrobapta (White, 1841) is removed from synonymy to denote the populations in Florida, Mexico and Brazil. Although the delimitation analyses suggest each of these geographic clusters within the L. argyrobapta samples represent different species, more specimens from Central and South America are needed to properly test the cohesion of L. argyrobapta populations.}, } @article {pmid29337273, year = {2018}, author = {Akand, EH and Downard, KM}, title = {Identification of epistatic mutations and insights into the evolution of the influenza virus using a mass-based protein phylogenetic approach.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {132-138}, doi = {10.1016/j.ympev.2018.01.009}, pmid = {29337273}, issn = {1095-9513}, mesh = {*Epistasis, Genetic ; *Evolution, Molecular ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Humans ; Influenza, Human/genetics/virology ; Molecular Weight ; Mutation/*genetics ; Mutation Rate ; Orthomyxoviridae/*metabolism ; *Phylogeny ; Viral Proteins/*metabolism ; }, abstract = {A mass-based protein phylogenetic approach developed in this laboratory has been applied to study mutation trends and identify consecutive or near-consecutive mutations typically associated with positive epistasis. While epistasis is thought to occur commonly during the evolution of viruses, the extent of epistasis in influenza, and its role in the evolution of immune escape and drug resistant mutants, remains to be systematically investigated. Here putative epistatic mutations within H3 hemagglutinin in type A influenza are identified where leading parent mutations were found to predominate within reported antigenic sites of the protein. Frequent subsequent mutations resided exclusively in different antigenic regions, providing the virus with a possible immune escape mechanism, or at other remote sites that drive beneficial protein structural and functional change. The results also enable a "small steps" evolutionary model to be proposed where the more frequent consecutive, or near-consecutive, non-conservative mutations exhibited less structural, and thus functional, change. This favours the evolutionary survival of the virus over mutations associated with more substantive change that may cause or risk its own extinction.}, } @article {pmid29337130, year = {2018}, author = {Lanza, AR and Seaver, EC}, title = {An organizing role for the TGF-β signaling pathway in axes formation of the annelid Capitella teleta.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {26-40}, doi = {10.1016/j.ydbio.2018.01.004}, pmid = {29337130}, issn = {1095-564X}, mesh = {Animals ; Benzamides/pharmacology ; Dioxoles/pharmacology ; Embryo, Nonmammalian/cytology/*embryology ; Polychaeta/cytology/*embryology ; Signal Transduction/drug effects/*physiology ; Transforming Growth Factor beta/*metabolism ; }, abstract = {Embryonic organizers are signaling centers that coordinate developmental events within an embryo. Localized to either an individual cell or group of cells, embryonic organizing activity induces the specification of other cells in the embryo and can influence formation of body axes. In the spiralian Capitella teleta, previous cell deletion studies have shown that organizing activity is localized to a single cell, 2d, and this cell induces the formation of the dorsal-ventral axis and bilateral symmetry. In this study, we attempt to identify the signaling pathway responsible for the organizing activity of 2d. Embryos at stages when organizing activity is occurring were exposed to various small molecule inhibitors that selectively inhibited either the Activin/Nodal or the BMP branch of the TGF-β signaling pathway. Embryos were then raised to larval stages, and scored for axial anomalies analogous to 2d ablated phenotypes. Our results show that interference with the Activin/Nodal pathway through a short three hour exposure to the inhibitor SB431542 results in larvae that lack bilateral symmetry and a detectable dorsal-ventral axis. However, interference with the BMP signaling pathway through exposure to the inhibitors DMH1 and dorsomorphin dihydrochloride does not appear to play a role in specification by 2d of the dorsal-ventral axis or bilateral symmetry. Our findings highlight species differences in how the molecular architecture of the conserved TGF-β superfamily signaling pathway components was utilized to mediate the organizing activity signal during early spiralian development.}, } @article {pmid29337129, year = {2018}, author = {Tominaga-Wada, R and Wada, T}, title = {Effect of amino acid substitution of CAPRICE on cell-to-cell movement ability in Arabidopsis root epidermis.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {1-5}, doi = {10.1016/j.ydbio.2018.01.002}, pmid = {29337129}, issn = {1095-564X}, mesh = {Amino Acid Motifs ; Amino Acid Substitution ; Arabidopsis/cytology/genetics/*metabolism ; Arabidopsis Proteins/genetics/*metabolism ; Cell Movement/*physiology ; *Mutation, Missense ; Plant Epidermis/cytology/genetics/*metabolism ; Plant Roots/cytology/genetics/*metabolism ; Proto-Oncogene Proteins c-myb/genetics/*metabolism ; }, abstract = {An R3-type MYB transcription factor, CAPRICE (CPC), is known to promote root hair cell differentiation in Arabidopsis root epidermis. The CPC protein moves from non-hair cells to the neighboring cells, and acts as an inducer of root hair formation. In contrast, we previously showed that the CPC homolog, ENHANCER OF TRY AND CPC1 (ETC1), does not move between the root epidermal cells. To clarify the critical difference in the cell-to-cell movement ability of CPC and ETC1 proteins, we generated five different chimeras of CPC and ETC1. As expected, four of the five chimeric proteins with substitution of CPC amino acids with those of ETC1 induced many root hair and no-trichome phenotype, like CPC. These chimeric proteins essentially maintained the cell-to-cell movement ability of CPC. However, one chimeric protein in which ETC1 was sandwiched between the CPC-specific movement motifs of S1 and S2 did not induce ectopic root hair formation. This chimeric protein did not move between the cells. These results indicate that the maintenance of not only the S1 and S2 motifs but also the precise structure of CPC protein might be necessary for the cell-to-cell movement of CPC. Our results should help in further unraveling of the roles of these MYB transcription factors in root hair formation.}, } @article {pmid29336985, year = {2018}, author = {Eisen, RJ and Eisen, L}, title = {The Blacklegged Tick, Ixodes scapularis: An Increasing Public Health Concern.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {295-309}, pmid = {29336985}, issn = {1471-5007}, support = {CC999999/ImCDC/Intramural CDC HHS/United States ; }, mesh = {Animal Distribution ; Animals ; Humans ; Incidence ; Ixodes/*parasitology/*physiology ; Tick-Borne Diseases/epidemiology/parasitology/*prevention & control/transmission ; United States ; }, abstract = {In the United States, the blacklegged tick, Ixodes scapularis, is a vector of seven human pathogens, including those causing Lyme disease, anaplasmosis, babesiosis, Borrelia miyamotoi disease, Powassan virus disease, and ehrlichiosis associated with Ehrlichia muris eauclarensis. In addition to an accelerated rate of discovery of I. scapularis-borne pathogens over the past two decades, the geographic range of the tick, and incidence and range of I. scapularis-borne disease cases, have increased. Despite knowledge of when and where humans are most at risk of exposure to infected ticks, control of I. scapularis-borne diseases remains a challenge. Human vaccines are not available, and we lack solid evidence for other prevention and control methods to reduce human disease. The way forward is discussed.}, } @article {pmid29336845, year = {2018}, author = {Boller, S and Li, R and Grosschedl, R}, title = {Defining B Cell Chromatin: Lessons from EBF1.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {257-269}, doi = {10.1016/j.tig.2017.12.014}, pmid = {29336845}, issn = {0168-9525}, mesh = {Animals ; B-Lymphocytes/cytology/*immunology ; Cell Differentiation ; Cell Lineage/genetics/immunology ; Chromatin/*chemistry/metabolism ; *Epigenesis, Genetic ; Gene Expression ; *Gene Regulatory Networks ; Histones/genetics/immunology ; Humans ; Lymphopoiesis/*genetics ; Stem Cells/cytology/immunology ; Trans-Activators/*genetics/immunology ; V(D)J Recombination ; }, abstract = {Hematopoiesis is regulated by signals from the microenvironment, transcription factor networks, and changes of the epigenetic landscape. Transcription factors interact with and shape chromatin to allow for lineage- and cell type-specific changes in gene expression. During B lymphopoiesis, epigenetic regulation is observed in multilineage progenitors in which a specific chromatin context is established, at the onset of the B cell differentiation when early B cell factor 1 (EBF1) induces lineage-specific changes in chromatin, during V(D)J recombination and after antigen-driven activation of B cells and terminal differentiation. In this review, we discuss the epigenetic changes underlying B cell differentiation, focusing on the role of transcription factor EBF1 in B cell lineage priming.}, } @article {pmid29336844, year = {2018}, author = {Song, AJ and Palmiter, RD}, title = {Detecting and Avoiding Problems When Using the Cre-lox System.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {5}, pages = {333-340}, pmid = {29336844}, issn = {0168-9525}, support = {/HHMI/Howard Hughes Medical Institute/United States ; P50 MH106428/MH/NIMH NIH HHS/United States ; R01 DA024908/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Embryonic Development/*genetics ; Gene Expression Regulation, Developmental/genetics ; Germ Cells/growth & development ; Integrases/*genetics ; Mice ; Mice, Transgenic/genetics ; *Recombination, Genetic ; }, abstract = {The Cre-lox recombination approach is commonly used to generate cell-specific gene inactivation (or activation). We have noticed that the breeding and genotyping sections of papers utilizing Cre-lox techniques are frequently incomplete. While seemingly straightforward, there are important considerations that need to be implemented in the breeding and genotyping methods to prevent the introduction of experimental confounds. Germline recombination and transient expression of Cre recombinase during development are some examples of the complications that can occur, and conventional genotyping methods may fail to identify these events. In this opinion article, we highlight the importance of testing for unexpected recombination events, suggest strategies to isolate and minimize adverse recombination events, and encourage editors and reviewers to expect more definitive statements regarding the validation of genotyping.}, } @article {pmid29336511, year = {2018}, author = {Hasegawa, M and Arai, E}, title = {Differential visual ornamentation between brood parasitic and parental cuckoos.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {446-456}, doi = {10.1111/jeb.13240}, pmid = {29336511}, issn = {1420-9101}, abstract = {The evolution of brood parasitism should affect adult phenotypic traits due to sexual selection as well as the parasite-host interactions, although it is rarely focused on. Sexual selection theory predicts extravagant secondary sexual characteristics in brood parasites whereas immature-like modest sexual characteristics in parental species. This is because juvenile-like immature traits can attract mates by exploiting parental care for young (i.e. attraction to young), and because the good parent process, which favours traits that signal parental care ability, would constrain the evolution of costly secondary sexual characteristics due to evolutionary trade-offs between parental investment and sexually selected traits. Using a phylogenetic comparative approach, we studied plumage and bare-part characteristics of adults in relation to brood parasitism in cuckoos (family Cuculidae), in which brood parasitism together with loss of parental care has evolved three times. As predicted, we found that nonparasitic cuckoos had plumage more similar to the juveniles than did brood parasitic cuckoos. Furthermore, nonparasitic cuckoos had a higher probability of having additional bare skin, that is a seemingly less costly, hatchling-like trait, than did brood parasitic cuckoos. This finding further supports the link between parental care and sexual selection, although the influence of a parasite-host interaction cannot be excluded. The analysis of evolutionary pathways suggested interdependent evolution of additional bare skin and brood parasitism. Brood parasitism together with the loss of parental care may prevent the maintenance of a modest phenotype similar to the young, and vice versa in some cases.}, } @article {pmid29336481, year = {2018}, author = {Sultanova, Z and Andic, M and Carazo, P}, title = {The "unguarded-X" and the genetic architecture of lifespan: Inbreeding results in a potentially maladaptive sex-specific reduction of female lifespan in Drosophila melanogaster.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {540-552}, doi = {10.1111/evo.13426}, pmid = {29336481}, issn = {1558-5646}, abstract = {Sex differences in ageing and lifespan are ubiquitous in nature. The "unguarded-X" hypothesis (UXh) suggests they may be partly due to the expression of recessive mutations in the hemizygous sex chromosomes of the heterogametic sex, which could help explain sex-specific ageing in a broad array of taxa. A prediction central to the UX hypothesis is that inbreeding will decrease the lifespan of the homogametic sex more than the heterogametic sex, because only in the former does inbreeding increase the expression of recessive deleterious mutations. In this study, we test this prediction by examining the effects of inbreeding on the lifespan and fitness of male and female Drosophila melanogaster across different social environments. We found that, across social environments, inbreeding resulted in a greater reduction of female than male lifespan, and that inbreeding effects on fitness did not seem to counterbalance sex-specific effects on lifespan, suggesting the former are maladaptative. Inter- and intra-sexual correlation analyses also allowed us to identify evidence of an underlying joint genetic architecture for inbreeding effects on lifespan. We discuss these results in light of the UXh and other alternative explanations, and suggest that more attention should be paid to the possibility that the "unguarded-X" may play an important role in the evolution of sex-specific lifespan.}, } @article {pmid29336088, year = {2018}, author = {Kasumovic, MM and Seebacher, F}, title = {Casual movement speed but not maximal locomotor capacity predicts mate searching success.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {438-445}, doi = {10.1111/jeb.13239}, pmid = {29336088}, issn = {1420-9101}, abstract = {Maximal locomotor performance is often used as a proxy for fitness. Maximal speed may be important under high-threat conditions, such as during predator escape. However, animals do not always move at a speed that reflects their maximal physiological capacities when undisturbed. The physiological factors that determine the movement speed chosen by animals, such as minimization of energy use, may be independent from maximal performance. As a result, the casual speed at which individuals move when undisturbed in a given context may better represent an individual's motivation to move. The casual speed may therefore be a better predictor of fitness in natural contexts than maximal performance capacity. We tested the hypothesis that casual movement speed rather than maximal speed predicts fitness in the golden orb-web spider, Nephila plumipes. We measured fitness in two separate contexts, mate-searching success and the positional rank near a female. We show that casual but not maximal locomotor speed predicted both aspects of fitness. Casual speed was linearly related to maximal speed, indicating that casual speed is determined by physiological optimization. Size and metabolic scope were not related to either maximal or chosen speeds, indicating that the supply of ATP does not limit locomotor performance in this species. Overall, our results demonstrate that locomotor performance is related to fitness, but suggest that different types of performance and not necessarily maximal physiological capacities are most relevant for particular ecologically relevant tasks.}, } @article {pmid29335803, year = {2018}, author = {Glinsky, GV}, title = {Contribution of transposable elements and distal enhancers to evolution of human-specific features of interphase chromatin architecture in embryonic stem cells.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {1-2}, pages = {61-84}, pmid = {29335803}, issn = {1573-6849}, mesh = {Chromatin/metabolism/*ultrastructure ; DNA Transposable Elements/*genetics ; Enhancer Elements, Genetic/*genetics ; *Evolution, Molecular ; Gene Regulatory Networks ; Genome, Human ; Human Embryonic Stem Cells/*ultrastructure ; Humans ; Interphase ; }, abstract = {Transposable elements have made major evolutionary impacts on creation of primate-specific and human-specific genomic regulatory loci and species-specific genomic regulatory networks (GRNs). Molecular and genetic definitions of human-specific changes to GRNs contributing to development of unique to human phenotypes remain a highly significant challenge. Genome-wide proximity placement analysis of diverse families of human-specific genomic regulatory loci (HSGRL) identified topologically associating domains (TADs) that are significantly enriched for HSGRL and designated rapidly evolving in human TADs. Here, the analysis of HSGRL, hESC-enriched enhancers, super-enhancers (SEs), and specific sub-TAD structures termed super-enhancer domains (SEDs) has been performed. In the hESC genome, 331 of 504 (66%) of SED-harboring TADs contain HSGRL and 68% of SEDs co-localize with HSGRL, suggesting that emergence of HSGRL may have rewired SED-associated GRNs within specific TADs by inserting novel and/or erasing existing non-coding regulatory sequences. Consequently, markedly distinct features of the principal regulatory structures of interphase chromatin evolved in the hESC genome compared to mouse: the SED quantity is 3-fold higher and the median SED size is significantly larger. Concomitantly, the overall TAD quantity is increased by 42% while the median TAD size is significantly decreased (p = 9.11E-37) in the hESC genome. Present analyses illustrate a putative global role for transposable elements and HSGRL in shaping the human-specific features of the interphase chromatin organization and functions, which are facilitated by accelerated creation of novel transcription factor binding sites and new enhancers driven by targeted placement of HSGRL at defined genomic coordinates. A trend toward the convergence of TAD and SED architectures of interphase chromatin in the hESC genome may reflect changes of 3D-folding patterns of linear chromatin fibers designed to enhance both regulatory complexity and functional precision of GRNs by creating predominantly a single gene (or a set of functionally linked genes) per regulatory domain structures. Collectively, present analyses reveal critical evolutionary contributions of transposable elements and distal enhancers to creation of thousands primate- and human-specific elements of a chromatin folding code, which defines the 3D context of interphase chromatin both restricting and facilitating biological functions of GRNs.}, } @article {pmid29335645, year = {2018}, author = {Plomin, R and von Stumm, S}, title = {The new genetics of intelligence.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {148-159}, pmid = {29335645}, issn = {1471-0064}, support = {R01 AG046938/AG/NIA NIH HHS/United States ; G0901245//Medical Research Council/United Kingdom ; G19/2//Medical Research Council/United Kingdom ; 295366//European Research Council/International ; MR/M021475/1//Medical Research Council/United Kingdom ; }, abstract = {Intelligence - the ability to learn, reason and solve problems - is at the forefront of behavioural genetic research. Intelligence is highly heritable and predicts important educational, occupational and health outcomes better than any other trait. Recent genome-wide association studies have successfully identified inherited genome sequence differences that account for 20% of the 50% heritability of intelligence. These findings open new avenues for research into the causes and consequences of intelligence using genome-wide polygenic scores that aggregate the effects of thousands of genetic variants.}, } @article {pmid29335644, year = {2018}, author = {Ceballos, FC and Joshi, PK and Clark, DW and Ramsay, M and Wilson, JF}, title = {Runs of homozygosity: windows into population history and trait architecture.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {220-234}, pmid = {29335644}, issn = {1471-0064}, abstract = {Long runs of homozygosity (ROH) arise when identical haplotypes are inherited from each parent and thus a long tract of genotypes is homozygous. Cousin marriage or inbreeding gives rise to such autozygosity; however, genome-wide data reveal that ROH are universally common in human genomes even among outbred individuals. The number and length of ROH reflect individual demographic history, while the homozygosity burden can be used to investigate the genetic architecture of complex disease. We discuss how to identify ROH in genome-wide microarray and sequence data, their distribution in human populations and their application to the understanding of inbreeding depression and disease risk.}, } @article {pmid29335578, year = {2018}, author = {Kaya, F and Bibi, F and Žliobaitė, I and Eronen, JT and Hui, T and Fortelius, M}, title = {Author Correction: The rise and fall of the Old World savannah fauna and the origins of the African savannah biome.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {402}, doi = {10.1038/s41559-018-0468-8}, pmid = {29335578}, issn = {2397-334X}, abstract = {In the version of this Article originally published, each of the five panels in Fig. 5 incorrectly contained a black diagonal line across the plot. This has now been corrected.}, } @article {pmid29335577, year = {2018}, author = {Vågene, ÅJ and Herbig, A and Campana, MG and Robles García, NM and Warinner, C and Sabin, S and Spyrou, MA and Andrades Valtueña, A and Huson, D and Tuross, N and Bos, KI and Krause, J}, title = {Salmonella enterica genomes from victims of a major sixteenth-century epidemic in Mexico.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {520-528}, doi = {10.1038/s41559-017-0446-6}, pmid = {29335577}, issn = {2397-334X}, abstract = {Indigenous populations of the Americas experienced high mortality rates during the early contact period as a result of infectious diseases, many of which were introduced by Europeans. Most of the pathogenic agents that caused these outbreaks remain unknown. Through the introduction of a new metagenomic analysis tool called MALT, applied here to search for traces of ancient pathogen DNA, we were able to identify Salmonella enterica in individuals buried in an early contact era epidemic cemetery at Teposcolula-Yucundaa, Oaxaca in southern Mexico. This cemetery is linked, based on historical and archaeological evidence, to the 1545-1550 CE epidemic that affected large parts of Mexico. Locally, this epidemic was known as 'cocoliztli', the pathogenic cause of which has been debated for more than a century. Here, we present genome-wide data from ten individuals for Salmonella enterica subsp. enterica serovar Paratyphi C, a bacterial cause of enteric fever. We propose that S. Paratyphi C be considered a strong candidate for the epidemic population decline during the 1545 cocoliztli outbreak at Teposcolula-Yucundaa.}, } @article {pmid29335576, year = {2018}, author = {Sano, EB and Wall, CA and Hutchins, PR and Miller, SR}, title = {Ancient balancing selection on heterocyst function in a cosmopolitan cyanobacterium.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {510-519}, doi = {10.1038/s41559-017-0435-9}, pmid = {29335576}, issn = {2397-334X}, abstract = {The conventional view of bacterial adaptation emphasizes the importance of rapidly evolved changes that are highly repeatable in response to similar environments and subject to loss in the absence of selection. Consequently, genetic variation is not expected to persist over long time scales for these organisms. Here, we show that a geographically widespread gene content polymorphism has surprisingly been maintained for tens of millions of years of diversification of the multicellular cyanobacterium Fischerella thermalis. The polymorphism affects gas permeability of the heterocyst-the oxygen-sensitive, nitrogen-fixing cell produced by these bacteria-and spatial variation in temperature favours alternative alleles due to thermodynamic effects on both heterocyst function and organism fitness at physiological temperature extremes. Whether or not ancient balancing selection plays a generally important role in the maintenance of microbial diversity remains to be investigated.}, } @article {pmid29335575, year = {2018}, author = {Milcu, A and Puga-Freitas, R and Ellison, AM and Blouin, M and Scheu, S and Freschet, GT and Rose, L and Barot, S and Cesarz, S and Eisenhauer, N and Girin, T and Assandri, D and Bonkowski, M and Buchmann, N and Butenschoen, O and Devidal, S and Gleixner, G and Gessler, A and Gigon, A and Greiner, A and Grignani, C and Hansart, A and Kayler, Z and Lange, M and Lata, JC and Le Galliard, JF and Lukac, M and Mannerheim, N and Müller, MEH and Pando, A and Rotter, P and Scherer-Lorenzen, M and Seyhun, R and Urban-Mead, K and Weigelt, A and Zavattaro, L and Roy, J}, title = {Genotypic variability enhances the reproducibility of an ecological study.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {279-287}, doi = {10.1038/s41559-017-0434-x}, pmid = {29335575}, issn = {2397-334X}, abstract = {Many scientific disciplines are currently experiencing a 'reproducibility crisis' because numerous scientific findings cannot be repeated consistently. A novel but controversial hypothesis postulates that stringent levels of environmental and biotic standardization in experimental studies reduce reproducibility by amplifying the impacts of laboratory-specific environmental factors not accounted for in study designs. A corollary to this hypothesis is that a deliberate introduction of controlled systematic variability (CSV) in experimental designs may lead to increased reproducibility. To test this hypothesis, we had 14 European laboratories run a simple microcosm experiment using grass (Brachypodium distachyon L.) monocultures and grass and legume (Medicago truncatula Gaertn.) mixtures. Each laboratory introduced environmental and genotypic CSV within and among replicated microcosms established in either growth chambers (with stringent control of environmental conditions) or glasshouses (with more variable environmental conditions). The introduction of genotypic CSV led to 18% lower among-laboratory variability in growth chambers, indicating increased reproducibility, but had no significant effect in glasshouses where reproducibility was generally lower. Environmental CSV had little effect on reproducibility. Although there are multiple causes for the 'reproducibility crisis', deliberately including genetic variability may be a simple solution for increasing the reproducibility of ecological studies performed under stringently controlled environmental conditions.}, } @article {pmid29335574, year = {2018}, author = {Muralidhar, P and Veller, C}, title = {Sexual antagonism and the instability of environmental sex determination.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {343-351}, doi = {10.1038/s41559-017-0427-9}, pmid = {29335574}, issn = {2397-334X}, abstract = {The sex of an organism can be determined by its genetics or its early environment. Across the animal kingdom, genetic sex determination (GSD) is far more common than environmental sex determination (ESD). Here, we propose an explanation for this pattern: the coupling of genes that bias offspring sex ratios towards one sex with genes that are beneficial in that sex but costly in the other. Gradual strengthening of the sex-specific tendency of this association eventuates in a neo-sex chromosome; that is, GSD. Our model predicts to which system of heterogamety ESD will evolve when nesting behaviour is an important determinant of brood sex ratios. It explains the puzzling observation in some GSD species of sex reversal induced by extreme environments. The model also suggests an approach to discovering sex-determining genes in ESD species.}, } @article {pmid29335573, year = {2018}, author = {Ringma, J and Legge, S and Woinarski, J and Radford, J and Wintle, B and Bode, M}, title = {Australia's mammal fauna requires a strategic and enhanced network of predator-free havens.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {410-411}, doi = {10.1038/s41559-017-0456-4}, pmid = {29335573}, issn = {2397-334X}, } @article {pmid29335572, year = {2018}, author = {Runemark, A and Trier, CN and Eroukhmanoff, F and Hermansen, JS and Matschiner, M and Ravinet, M and Elgvin, TO and Sætre, GP}, title = {Variation and constraints in hybrid genome formation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {549-556}, doi = {10.1038/s41559-017-0437-7}, pmid = {29335572}, issn = {2397-334X}, abstract = {Hybridization is an important source of variation; it transfers adaptive genetic variation across species boundaries and generates new species. Yet, the limits to viable hybrid genome formation are poorly understood. Here we investigated to what extent hybrid genomes are free to evolve by sequencing the genomes of four island populations of the homoploid hybrid Italian sparrow Passer italiae. We report that a variety of novel and fully functional hybrid genomic combinations are likely to have arisen independently on Crete, Corsica, Sicily and Malta, with differentiation in candidate genes for beak shape and plumage colour. However, certain genomic regions are invariably inherited from the same parent species, limiting variation. These regions are over-represented on the Z chromosome and harbour candidate incompatibility loci, including DNA-repair and mitonuclear genes. These gene classes may contribute to the general reduction of introgression on sex chromosomes. This study demonstrates that hybrid genomes may vary, and identifies new candidate reproductive isolation genes.}, } @article {pmid29335571, year = {2018}, author = {Lechner, AM and Chan, FKS and Campos-Arceiz, A}, title = {Biodiversity conservation should be a core value of China's Belt and Road Initiative.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {408-409}, doi = {10.1038/s41559-017-0452-8}, pmid = {29335571}, issn = {2397-334X}, } @article {pmid29335570, year = {2018}, author = {Di Minin, E and Fink, C and Tenkanen, H and Hiippala, T}, title = {Machine learning for tracking illegal wildlife trade on social media.}, journal = {Nature ecology & evolution}, volume = {2}, number = {3}, pages = {406-407}, doi = {10.1038/s41559-018-0466-x}, pmid = {29335570}, issn = {2397-334X}, } @article {pmid29335555, year = {2018}, author = {Abu-Ali, GS and Mehta, RS and Lloyd-Price, J and Mallick, H and Branck, T and Ivey, KL and Drew, DA and DuLong, C and Rimm, E and Izard, J and Chan, AT and Huttenhower, C}, title = {Metatranscriptome of human faecal microbial communities in a cohort of adult men.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {356-366}, doi = {10.1038/s41564-017-0084-4}, pmid = {29335555}, issn = {2058-5276}, abstract = {The gut microbiome is intimately related to human health, but it is not yet known which functional activities are driven by specific microorganisms' ecological configurations or transcription. We report a large-scale investigation of 372 human faecal metatranscriptomes and 929 metagenomes from a subset of 308 men in the Health Professionals Follow-Up Study. We identified a metatranscriptomic 'core' universally transcribed over time and across participants, often by different microorganisms. In contrast to the housekeeping functions enriched in this core, a 'variable' metatranscriptome included specialized pathways that were differentially expressed both across participants and among microorganisms. Finally, longitudinal metagenomic profiles allowed ecological interaction network reconstruction, which remained stable over the six-month timespan, as did strain tracking within and between participants. These results provide an initial characterization of human faecal microbial ecology into core, subject-specific, microorganism-specific and temporally variable transcription, and they differentiate metagenomically versus metatranscriptomically informative aspects of the human faecal microbiome.}, } @article {pmid29335554, year = {2018}, author = {Mehta, RS and Abu-Ali, GS and Drew, DA and Lloyd-Price, J and Subramanian, A and Lochhead, P and Joshi, AD and Ivey, KL and Khalili, H and Brown, GT and DuLong, C and Song, M and Nguyen, LH and Mallick, H and Rimm, EB and Izard, J and Huttenhower, C and Chan, AT}, title = {Stability of the human faecal microbiome in a cohort of adult men.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {347-355}, pmid = {29335554}, issn = {2058-5276}, support = {P30 DK043351/DK/NIDDK NIH HHS/United States ; K01 DK110267/DK/NIDDK NIH HHS/United States ; R01 CA202704/CA/NCI NIH HHS/United States ; U01 CA152904/CA/NCI NIH HHS/United States ; K24 DK098311/DK/NIDDK NIH HHS/United States ; U54 DE023798/DE/NIDCR NIH HHS/United States ; UM1 CA167552/CA/NCI NIH HHS/United States ; R01 HL035464/HL/NHLBI NIH HHS/United States ; }, abstract = {Characterizing the stability of the gut microbiome is important to exploit it as a therapeutic target and diagnostic biomarker. We metagenomically and metatranscriptomically sequenced the faecal microbiomes of 308 participants in the Health Professionals Follow-Up Study. Participants provided four stool samples-one pair collected 24-72 h apart and a second pair ~6 months later. Within-person taxonomic and functional variation was consistently lower than between-person variation over time. In contrast, metatranscriptomic profiles were comparably variable within and between subjects due to higher within-subject longitudinal variation. Metagenomic instability accounted for ~74% of corresponding metatranscriptomic instability. The rest was probably attributable to sources such as regulation. Among the pathways that were differentially regulated, most were consistently over- or under-transcribed at each time point. Together, these results suggest that a single measurement of the faecal microbiome can provide long-term information regarding organismal composition and functional potential, but repeated or short-term measures may be necessary for dynamic features identified by metatranscriptomics.}, } @article {pmid29335553, year = {2018}, author = {Ates, LS and Dippenaar, A and Ummels, R and Piersma, SR and van der Woude, AD and van der Kuij, K and Le Chevalier, F and Mata-Espinosa, D and Barrios-Payán, J and Marquina-Castillo, B and Guapillo, C and Jiménez, CR and Pain, A and Houben, ENG and Warren, RM and Brosch, R and Hernández-Pando, R and Bitter, W}, title = {Mutations in ppe38 block PE_PGRS secretion and increase virulence of Mycobacterium tuberculosis.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {181-188}, doi = {10.1038/s41564-017-0090-6}, pmid = {29335553}, issn = {2058-5276}, abstract = {Mycobacterium tuberculosis requires a large number of secreted and exported proteins for its virulence, immune modulation and nutrient uptake. Most of these proteins are transported by the different type VII secretion systems1,2. The most recently evolved type VII secretion system, ESX-5, secretes dozens of substrates belonging to the PE and PPE families, which are named for conserved proline and glutamic acid residues close to the amino terminus3,4. However, the role of these proteins remains largely elusive 1 . Here, we show that mutations of ppe38 completely block the secretion of two large subsets of ESX-5 substrates, that is, PPE-MPTR and PE_PGRS, together comprising >80 proteins. Importantly, hypervirulent clinical M. tuberculosis strains of the Beijing lineage have such a mutation and a concomitant loss of secretion 5 . Restoration of PPE38-dependent secretion partially reverted the hypervirulence phenotype of a Beijing strain, and deletion of ppe38 in moderately virulent M. tuberculosis increased virulence. This indicates that these ESX-5 substrates have an important role in virulence attenuation. Phylogenetic analysis revealed that deletion of ppe38 occurred at the branching point of the 'modern' Beijing sublineage and is shared by Beijing outbreak strains worldwide, suggesting that this deletion may have contributed to their success and global distribution6,7.}, } @article {pmid29335552, year = {2018}, author = {Zheng, Y and Harris, DF and Yu, Z and Fu, Y and Poudel, S and Ledbetter, RN and Fixen, KR and Yang, ZY and Boyd, ES and Lidstrom, ME and Seefeldt, LC and Harwood, CS}, title = {A pathway for biological methane production using bacterial iron-only nitrogenase.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {281-286}, doi = {10.1038/s41564-017-0091-5}, pmid = {29335552}, issn = {2058-5276}, abstract = {Methane (CH4) is a potent greenhouse gas that is released from fossil fuels and is also produced by microbial activity, with at least one billion tonnes of CH4 being formed and consumed by microorganisms in a single year 1 . Complex methanogenesis pathways used by archaea are the main route for bioconversion of carbon dioxide (CO2) to CH4 in nature2-4. Here, we report that wild-type iron-iron (Fe-only) nitrogenase from the bacterium Rhodopseudomonas palustris reduces CO2 simultaneously with nitrogen gas (N2) and protons to yield CH4, ammonia (NH3) and hydrogen gas (H2) in a single enzymatic step. The amount of CH4 produced by purified Fe-only nitrogenase was low compared to its other products, but CH4 production by this enzyme in R. palustris was sufficient to support the growth of an obligate CH4-utilizing Methylomonas strain when the two microorganisms were grown in co-culture, with oxygen (O2) added at intervals. Other nitrogen-fixing bacteria that we tested also formed CH4 when expressing Fe-only nitrogenase, suggesting that this is a general property of this enzyme. The genomes of 9% of diverse nitrogen-fixing microorganisms from a range of environments encode Fe-only nitrogenase. Our data suggest that active Fe-only nitrogenase, present in diverse microorganisms, contributes CH4 that could shape microbial community interactions.}, } @article {pmid29335549, year = {2018}, author = {Jagadeesan, A and Gunnarsdóttir, ED and Ebenesersdóttir, SS and Guðmundsdóttir, VB and Thordardottir, EL and Einarsdóttir, MS and Jónsson, H and Dugoujon, JM and Fortes-Lima, C and Migot-Nabias, F and Massougbodji, A and Bellis, G and Pereira, L and Másson, G and Kong, A and Stefánsson, K and Helgason, A}, title = {Reconstructing an African haploid genome from the 18th century.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {199-205}, doi = {10.1038/s41588-017-0031-6}, pmid = {29335549}, issn = {1546-1718}, abstract = {A genome is a mosaic of chromosome fragments from ancestors who existed some arbitrary number of generations earlier. Here, we reconstruct the genome of Hans Jonatan (HJ), born in the Caribbean in 1784 to an enslaved African mother and European father. HJ migrated to Iceland in 1802, married and had two children. We genotyped 182 of his 788 descendants using single-nucleotide polymorphism (SNP) chips and whole-genome sequenced (WGS) 20 of them. Using these data, we reconstructed 38% of HJ's maternal genome and inferred that his mother was from the region spanned by Benin, Nigeria and Cameroon.}, } @article {pmid29335548, year = {2018}, author = {Martinez, G and Wolff, P and Wang, Z and Moreno-Romero, J and Santos-González, J and Conze, LL and DeFraia, C and Slotkin, RK and Köhler, C}, title = {Paternal easiRNAs regulate parental genome dosage in Arabidopsis.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {193-198}, doi = {10.1038/s41588-017-0033-4}, pmid = {29335548}, issn = {1546-1718}, abstract = {The regulation of parental genome dosage is of fundamental importance in animals and plants, as exemplified by X-chromosome inactivation and dosage compensation. The 'triploid block' is a classic example of dosage regulation in plants that establishes a reproductive barrier between species differing in chromosome number1,2. This barrier acts in the embryo-nourishing endosperm tissue and induces the abortion of hybrid seeds through a yet unknown mechanism 3 . Here we show that depletion of paternal epigenetically activated small interfering RNAs (easiRNAs) bypasses the triploid block in response to increased paternal ploidy in Arabidopsis thaliana. Paternal loss of the plant-specific RNA polymerase IV suppressed easiRNA formation and rescued triploid seeds by restoring small-RNA-directed DNA methylation at transposable elements (TEs), correlating with reduced expression of paternally expressed imprinted genes (PEGs). Our data suggest that easiRNAs form a quantitative signal for paternal chromosome number and that their balanced dosage is required for post-fertilization genome stability and seed viability.}, } @article {pmid29335547, year = {2018}, author = {Zhao, Q and Feng, Q and Lu, H and Li, Y and Wang, A and Tian, Q and Zhan, Q and Lu, Y and Zhang, L and Huang, T and Wang, Y and Fan, D and Zhao, Y and Wang, Z and Zhou, C and Chen, J and Zhu, C and Li, W and Weng, Q and Xu, Q and Wang, ZX and Wei, X and Han, B and Huang, X}, title = {Pan-genome analysis highlights the extent of genomic variation in cultivated and wild rice.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {278-284}, doi = {10.1038/s41588-018-0041-z}, pmid = {29335547}, issn = {1546-1718}, abstract = {The rich genetic diversity in Oryza sativa and Oryza rufipogon serves as the main sources in rice breeding. Large-scale resequencing has been undertaken to discover allelic variants in rice, but much of the information for genetic variation is often lost by direct mapping of short sequence reads onto the O. sativa japonica Nipponbare reference genome. Here we constructed a pan-genome dataset of the O. sativa-O. rufipogon species complex through deep sequencing and de novo assembly of 66 divergent accessions. Intergenomic comparisons identified 23 million sequence variants in the rice genome. This catalog of sequence variations includes many known quantitative trait nucleotides and will be helpful in pinpointing new causal variants that underlie complex traits. In particular, we systemically investigated the whole set of coding genes using this pan-genome data, which revealed extensive presence and absence of variation among rice accessions. This pan-genome resource will further promote evolutionary and functional studies in rice.}, } @article {pmid29335546, year = {2018}, author = {Stadhouders, R and Vidal, E and Serra, F and Di Stefano, B and Le Dily, F and Quilez, J and Gomez, A and Collombet, S and Berenguer, C and Cuartero, Y and Hecht, J and Filion, GJ and Beato, M and Marti-Renom, MA and Graf, T}, title = {Transcription factors orchestrate dynamic interplay between genome topology and gene regulation during cell reprogramming.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {238-249}, pmid = {29335546}, issn = {1546-1718}, support = {609989//European Research Council/International ; }, abstract = {Chromosomal architecture is known to influence gene expression, yet its role in controlling cell fate remains poorly understood. Reprogramming of somatic cells into pluripotent stem cells (PSCs) by the transcription factors (TFs) OCT4, SOX2, KLF4 and MYC offers an opportunity to address this question but is severely limited by the low proportion of responding cells. We have recently developed a highly efficient reprogramming protocol that synchronously converts somatic into pluripotent stem cells. Here, we used this system to integrate time-resolved changes in genome topology with gene expression, TF binding and chromatin-state dynamics. The results showed that TFs drive topological genome reorganization at multiple architectural levels, often before changes in gene expression. Removal of locus-specific topological barriers can explain why pluripotency genes are activated sequentially, instead of simultaneously, during reprogramming. Together, our results implicate genome topology as an instructive force for implementing transcriptional programs and cell fate in mammals.}, } @article {pmid29335545, year = {2018}, author = {Chen, M and Zhang, J and Sampieri, K and Clohessy, JG and Mendez, L and Gonzalez-Billalabeitia, E and Liu, XS and Lee, YR and Fung, J and Katon, JM and Menon, AV and Webster, KA and Ng, C and Palumbieri, MD and Diolombi, MS and Breitkopf, SB and Teruya-Feldstein, J and Signoretti, S and Bronson, RT and Asara, JM and Castillo-Martin, M and Cordon-Cardo, C and Pandolfi, PP}, title = {An aberrant SREBP-dependent lipogenic program promotes metastatic prostate cancer.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {206-218}, doi = {10.1038/s41588-017-0027-2}, pmid = {29335545}, issn = {1546-1718}, abstract = {Lipids, either endogenously synthesized or exogenous, have been linked to human cancer. Here we found that PML is frequently co-deleted with PTEN in metastatic human prostate cancer (CaP). We demonstrated that conditional inactivation of Pml in the mouse prostate morphs indolent Pten-null tumors into lethal metastatic disease. We identified MAPK reactivation, subsequent hyperactivation of an aberrant SREBP prometastatic lipogenic program, and a distinctive lipidomic profile as key characteristic features of metastatic Pml and Pten double-null CaP. Furthermore, targeting SREBP in vivo by fatostatin blocked both tumor growth and distant metastasis. Importantly, a high-fat diet (HFD) induced lipid accumulation in prostate tumors and was sufficient to drive metastasis in a nonmetastatic Pten-null mouse model of CaP, and an SREBP signature was highly enriched in metastatic human CaP. Thus, our findings uncover a prometastatic lipogenic program and lend direct genetic and experimental support to the notion that a Western HFD can promote metastasis.}, } @article {pmid29335544, year = {2018}, author = {Borges, F and Parent, JS and van Ex, F and Wolff, P and Martínez, G and Köhler, C and Martienssen, RA}, title = {Transposon-derived small RNAs triggered by miR845 mediate genome dosage response in Arabidopsis.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {186-192}, pmid = {29335544}, issn = {1546-1718}, support = {//Howard Hughes Medical Institute/United States ; P30 CA045508/CA/NCI NIH HHS/United States ; R01 GM067014/GM/NIGMS NIH HHS/United States ; S10 OD020122/OD/NIH HHS/United States ; }, abstract = {Chromosome dosage has substantial effects on reproductive isolation and speciation in both plants and animals, but the underlying mechanisms are largely obscure 1 . Transposable elements in animals can regulate hybridity through maternal small RNA 2 , whereas small RNAs in plants have been postulated to regulate dosage response via neighboring imprinted genes3,4. Here we show that a highly conserved microRNA in plants, miR845, targets the tRNAMet primer-binding site (PBS) of long terminal repeat (LTR) retrotransposons in Arabidopsis pollen, and triggers the accumulation of 21-22-nucleotide (nt) small RNAs in a dose-dependent fashion via RNA polymerase IV. We show that these epigenetically activated small interfering RNAs (easiRNAs) mediate hybridization barriers between diploid seed parents and tetraploid pollen parents (the 'triploid block'), and that natural variation for miR845 may account for 'endosperm balance' allowing the formation of triploid seeds. Targeting of the PBS with small RNA is a common mechanism for transposon control in mammals and plants, and provides a uniquely sensitive means to monitor chromosome dosage and imprinting in the developing seed.}, } @article {pmid29335543, year = {2018}, author = {Poulose, N and Amoroso, F and Steele, RE and Singh, R and Ong, CW and Mills, IG}, title = {Genetics of lipid metabolism in prostate cancer.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {169-171}, doi = {10.1038/s41588-017-0037-0}, pmid = {29335543}, issn = {1546-1718}, } @article {pmid29335542, year = {2018}, author = {Chen, J and Guccini, I and Di Mitri, D and Brina, D and Revandkar, A and Sarti, M and Pasquini, E and Alajati, A and Pinton, S and Losa, M and Civenni, G and Catapano, CV and Sgrignani, J and Cavalli, A and D'Antuono, R and Asara, JM and Morandi, A and Chiarugi, P and Crotti, S and Agostini, M and Montopoli, M and Masgras, I and Rasola, A and Garcia-Escudero, R and Delaleu, N and Rinaldi, A and Bertoni, F and Bono, J and Carracedo, A and Alimonti, A}, title = {Compartmentalized activities of the pyruvate dehydrogenase complex sustain lipogenesis in prostate cancer.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {219-228}, pmid = {29335542}, issn = {1546-1718}, support = {261342//European Research Council/International ; 336343//European Research Council/International ; P01 CA120964/CA/NCI NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; }, abstract = {The mechanisms by which mitochondrial metabolism supports cancer anabolism remain unclear. Here, we found that genetic and pharmacological inactivation of pyruvate dehydrogenase A1 (PDHA1), a subunit of the pyruvate dehydrogenase complex (PDC), inhibits prostate cancer development in mouse and human xenograft tumor models by affecting lipid biosynthesis. Mechanistically, we show that in prostate cancer, PDC localizes in both the mitochondria and the nucleus. Whereas nuclear PDC controls the expression of sterol regulatory element-binding transcription factor (SREBF)-target genes by mediating histone acetylation, mitochondrial PDC provides cytosolic citrate for lipid synthesis in a coordinated manner, thereby sustaining anabolism. Additionally, we found that PDHA1 and the PDC activator pyruvate dehydrogenase phosphatase 1 (PDP1) are frequently amplified and overexpressed at both the gene and protein levels in prostate tumors. Together, these findings demonstrate that both mitochondrial and nuclear PDC sustain prostate tumorigenesis by controlling lipid biosynthesis, thus suggesting this complex as a potential target for cancer therapy.}, } @article {pmid29335383, year = {2018}, author = {Speijer, D}, title = {Response to Ghiselli F et al. (2018).}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335383}, issn = {1471-2970}, mesh = {*Eukaryota ; }, } @article {pmid29335382, year = {2018}, author = {Aviv, A}, title = {The mitochondrial genome, paternal age and telomere length in humans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335382}, issn = {1471-2970}, support = {R01 HL116446/HL/NHLBI NIH HHS/United States ; R01 HD071180/HD/NICHD NIH HHS/United States ; R01 HL134840/HL/NHLBI NIH HHS/United States ; }, mesh = {Biological Evolution ; *Genome, Mitochondrial ; Humans ; Male ; *Paternal Age ; Polymorphism, Genetic ; Reactive Oxygen Species/metabolism ; Spermatozoa/metabolism ; Stem Cells ; Telomere/*metabolism ; *Telomere Homeostasis ; }, abstract = {Telomere length (TL) in humans is highly heritable and undergoes progressive age-dependent shortening in somatic cells. By contrast, sperm donated by older men display comparatively long telomeres, presumably because in the male germline, telomeres become longer with age. This puzzling phenomenon might explain why TL in the offspring correlates positively with paternal age. The present communication proposes that mitochondrial DNA polymorphisms and heteroplasmy cause variation in the production of reactive oxygen species, which, in turn, mediate age-dependent selection of germ stem cells with long telomeres and hence sperm with long telomeres. These long telomeres are then inherited by the offspring. The effect of paternal age on the offspring TL might be an evolutionarily driven mechanism that helps regulate TL across the human population.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335381, year = {2018}, author = {Entringer, S and de Punder, K and Buss, C and Wadhwa, PD}, title = {The fetal programming of telomere biology hypothesis: an update.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335381}, issn = {1471-2970}, support = {R01 AG050455/AG/NIA NIH HHS/United States ; R01 HD060628/HD/NICHD NIH HHS/United States ; R01 HD065825/HD/NICHD NIH HHS/United States ; UG3 OD023349/OD/NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Disease Susceptibility ; Female ; *Fetal Development ; Humans ; Infant, Newborn ; Oxidative Stress ; Placenta/metabolism ; Pregnancy ; Risk Factors ; Stress, Psychological ; Telomerase/*metabolism ; Telomere/*metabolism ; *Telomere Homeostasis ; }, abstract = {Research on mechanisms underlying fetal programming of health and disease risk has focused primarily on processes that are specific to cell types, organs or phenotypes of interest. However, the observation that developmental conditions concomitantly influence a diverse set of phenotypes, the majority of which are implicated in age-related disorders, raises the possibility that such developmental conditions may additionally exert effects via a common underlying mechanism that involves cellular/molecular ageing-related processes. In this context, we submit that telomere biology represents a process of particular interest in humans because, firstly, this system represents among the most salient antecedent cellular phenotypes for common age-related disorders; secondly, its initial (newborn) setting appears to be particularly important for its long-term effects; and thirdly, its initial setting appears to be plastic and under developmental regulation. We propose that the effects of suboptimal intrauterine conditions on the initial setting of telomere length and telomerase expression/activity capacity may be mediated by the programming actions of stress-related maternal-placental-fetal oxidative, immune, endocrine and metabolic pathways in a manner that may ultimately accelerate cellular dysfunction, ageing and disease susceptibility over the lifespan. This perspectives paper provides an overview of each of the elements underlying this hypothesis, with an emphasis on recent developments, findings and future directions.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335380, year = {2018}, author = {Ghiselli, F and Breton, S and Milani, L}, title = {Mitochondrial activity in gametes and uniparental inheritance: a comment on 'What can we infer about the origin of sex in early eukaryotes?'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335380}, issn = {1471-2970}, mesh = {DNA, Mitochondrial ; Eukaryota/*genetics ; Germ Cells ; Mitochondria/*genetics ; }, } @article {pmid29335379, year = {2018}, author = {Young, AJ}, title = {The role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335379}, issn = {1471-2970}, support = {BB/H022716/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adaptation, Physiological ; Aging/*genetics ; Animals ; *Biological Evolution ; Cellular Senescence ; Humans ; Telomere/*physiology ; *Telomere Homeostasis ; Telomere Shortening ; }, abstract = {Evolutionary biology and biomedicine have seen a surge of recent interest in the possibility that telomeres play a role in life-history trade-offs and ageing. Here, I evaluate alternative hypotheses for the role of telomeres in the mechanisms and evolution of life-history trade-offs and ageing, and highlight outstanding challenges. First, while recent findings underscore the possibility of a proximate causal role for telomeres in current-future trade-offs and ageing, it is currently unclear (i) whether telomeres ever play a causal role in either and (ii) whether any causal role for telomeres arises via shortening or length-independent mechanisms. Second, I consider why, if telomeres do play a proximate causal role, selection has not decoupled such a telomere-mediated trade-off between current and future performance. Evidence suggests that evolutionary constraints have not rendered such decoupling impossible. Instead, a causal role for telomeres would more plausibly reflect an adaptive strategy, born of telomere maintenance costs and/or a function for telomere attrition (e.g. in countering cancer), the relative importance of which is currently unclear. Finally, I consider the potential for telomere biology to clarify the constraints at play in life-history evolution, and to explain the form of the current-future trade-offs and ageing trajectories that we observe today.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335378, year = {2018}, author = {Lai, TP and Wright, WE and Shay, JW}, title = {Comparison of telomere length measurement methods.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335378}, issn = {1471-2970}, mesh = {Animals ; Cellular Senescence/genetics ; Humans ; *In Situ Hybridization, Fluorescence ; *Real-Time Polymerase Chain Reaction ; Reproducibility of Results ; Sensitivity and Specificity ; Telomere/*genetics ; *Telomere Homeostasis ; Validation Studies as Topic ; }, abstract = {The strengths and limitations of the major methods developed to measure telomere lengths (TLs) in cells and tissues are presented in this review. These include Q-PCR (Quantitative Polymerase Chain Reaction), TRF (Terminal Restriction Fragment) analysis, a variety of Q-FISH (Quantitative Fluorescence In Situ Hybridization) methods, STELA (Single TElomere Length Analysis) and TeSLA (Telomere Shortest Length Assay). For each method, we will cover information about validation studies, including reproducibility in independent laboratories, accuracy, reliability and sensitivity for measuring not only the average but also the shortest telomeres. There is substantial evidence that it is the shortest telomeres that trigger DNA damage responses leading to replicative senescence in mammals. However, the most commonly used TL measurement methods generally provide information on average or relative TL, but it is the shortest telomeres that leads to telomere dysfunction (identified by TIF, Telomere dysfunction Induced Foci) and limit cell proliferation in the absence of a telomere maintenance mechanism, such as telomerase. As the length of the shortest telomeres is a key biomarker determining cell fate and the onset of senescence, a new technique (TeSLA) that provides quantitative information about all the shortest telomeres will be highlighted.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335377, year = {2018}, author = {Dugdale, HL and Richardson, DS}, title = {Heritability of telomere variation: it is all about the environment!.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335377}, issn = {1471-2970}, mesh = {Age Factors ; Animals ; Biological Evolution ; *Environment ; *Genetic Variation ; Humans ; Linear Models ; Telomere/*genetics ; *Telomere Homeostasis ; Time Factors ; }, abstract = {Individual differences in telomere length have been linked to survival and senescence. Understanding the heritability of telomere length can provide important insight into individual differences and facilitate our understanding of the evolution of telomeres. However, to gain accurate and meaningful estimates of telomere heritability it is vital that the impact of the environment, and how this may vary, is understood and accounted for. The aim of this review is to raise awareness of this important, but much under-appreciated point. We outline the factors known to impact telomere length and discuss the fact that telomere length is a trait that changes with age. We highlight statistical methods that can separate genetic from environmental effects and control for confounding variables. We then review how well previous studies in vertebrate populations including humans have taken these factors into account. We argue that studies to date either use methodological techniques that confound environmental and genetic effects, or use appropriate methods but lack sufficient power to fully separate these components. We discuss potential solutions. We conclude that we need larger studies, which also span longer time periods, to account for changing environmental effects, if we are to determine meaningful estimates of the genetic component of telomere length.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335376, year = {2018}, author = {Baird, DM}, title = {Telomeres and genomic evolution.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335376}, issn = {1471-2970}, support = {C17199/A18246//Cancer Research UK/International ; }, mesh = {Chromosomal Instability ; Chromosomes/genetics ; *Evolution, Molecular ; Genetic Variation ; Humans ; Neoplasms/genetics ; Recombinational DNA Repair ; Telomere/*genetics ; *Telomere Homeostasis ; }, abstract = {The terminal regions of eukaryotic chromosomes, composed of telomere repeat sequences and sub-telomeric sequences, represent some of the most variable and rapidly evolving regions of the genome. The sub-telomeric regions are characterized by segmentally duplicated repetitive DNA elements, interstitial telomere repeat sequences and families of variable genes. Sub-telomeric repeat sequence families are shared among multiple chromosome ends, often rendering detailed sequence characterization difficult. These regions are composed of constitutive heterochromatin and are subjected to high levels of meiotic recombination. Dysfunction within telomere repeat arrays, either due to disruption in the chromatin structure or because of telomere shortening, can lead to chromosomal fusion and the generation of large-scale genomic rearrangements across the genome. The dynamic nature of telomeric regions, therefore, provides functionally useful variation to create genetic diversity, but also provides a mechanism for rapid genomic evolution that can lead to reproductive isolation and speciation. This article is part of the theme issue 'Understanding diversity in telomere dynamics'.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335375, year = {2018}, author = {Aviv, A and Shay, JW}, title = {Reflections on telomere dynamics and ageing-related diseases in humans.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335375}, issn = {1471-2970}, mesh = {Aging/*genetics ; Animals ; Cardiovascular Diseases/*genetics ; Child ; Female ; Humans ; Infant, Newborn ; Longevity ; Male ; Mice ; Neoplasms/*genetics ; Paternal Age ; Race Factors ; Sex Factors ; Telomere/*genetics ; *Telomere Homeostasis ; }, abstract = {Epidemiological studies have principally relied on measurements of telomere length (TL) in leucocytes, which reflects TL in other somatic cells. Leucocyte TL (LTL) displays vast variation across individuals-a phenomenon already observed in newborns. It is highly heritable, longer in females than males and in individuals of African ancestry than European ancestry. LTL is also longer in offspring conceived by older men. The traditional view regards LTL as a passive biomarker of human ageing. However, new evidence suggests that a dynamic interplay between selective evolutionary forces and TL might result in trade-offs for specific health outcomes. From a biological perspective, an active role of TL in ageing-related human diseases could occur because short telomeres increase the risk of a category of diseases related to restricted cell proliferation and tissue degeneration, including cardiovascular disease, whereas long telomeres increase the risk of another category of diseases related to increased proliferative growth, including major cancers. To understand the role of telomere biology in ageing-related diseases, it is essential to expand telomere research to newborns and children and seek further insight into the underlying causes of the variation in TL due to ancestry and geographical location.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335374, year = {2018}, author = {Monaghan, P and Eisenberg, DTA and Harrington, L and Nussey, D}, title = {Understanding diversity in telomere dynamics.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335374}, issn = {1471-2970}, support = {BB/H021868/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Biological Evolution ; Chromosomal Instability ; *Genetic Variation ; Humans ; Longevity ; Mutation ; Telomerase/metabolism ; Telomere/*genetics ; *Telomere Homeostasis ; Telomere Shortening ; }, } @article {pmid29335373, year = {2018}, author = {Olsson, M and Wapstra, E and Friesen, C}, title = {Ectothermic telomeres: it's time they came in from the cold.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335373}, issn = {1471-2970}, mesh = {Animals ; *Body Temperature ; Fishes/genetics ; Neoplasms/metabolism ; Plants/genetics ; Reptiles/genetics ; Risk Factors ; Telomerase/metabolism ; Telomere/*genetics/metabolism ; *Telomere Homeostasis ; }, abstract = {We review the evolutionary ecology and genetics of telomeres in taxa that cannot elevate their body temperature to a preferred level through metabolism but do so by basking or seeking out a warm environment. This group of organisms contains all living things on earth, apart from birds and mammals. One reason for our interest in this synthetic group is the argument that high, stable body temperature increases the risk of malignant tumours if long, telomerase-restored telomeres make cells 'live forever'. If this holds true, ectotherms should have significantly lower cancer frequencies. We discuss to what degree there is support for this 'anti-cancer' hypothesis in the current literature. Importantly, we suggest that ectothermic taxa, with variation in somatic telomerase expression across tissue and taxa, may hold the key to understanding ongoing selection and evolution of telomerase dynamics in the wild. We further review endotherm-specific effects of growth on telomeres, effects of autotomy ('tail dropping') on telomere attrition, and costs of maintaining sexual displays measured in telomere attrition. Finally, we cover plant ectotherm telomeres and life histories in a separate 'mini review'.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335372, year = {2018}, author = {Risques, RA and Promislow, DEL}, title = {All's well that ends well: why large species have short telomeres.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335372}, issn = {1471-2970}, support = {R01 CA181308/CA/NCI NIH HHS/United States ; }, mesh = {Age Factors ; Animals ; Biological Evolution ; *Body Size ; Cellular Senescence ; Female ; Humans ; Male ; Mammals/genetics/*growth & development ; Models, Theoretical ; Neoplasms/*mortality ; Telomerase/metabolism ; Telomere/*metabolism ; *Telomere Shortening ; }, abstract = {Among mammal species, almost all life-history traits are strongly size dependent. This size dependence even occurs at a molecular level. For example, both telomere length and telomerase expression show a size-dependent threshold. With some exceptions, species smaller than approximately 2 kg express telomerase, while species larger than that do not. Among species greater than approximately 5 kg, telomeres tend to be short-less than 25 kb-while among smaller species, some species have short and some have long telomeres. Here, we present a model to explore the role of body size-dependent trade-offs in shaping this threshold. We assume that selection favours short telomeres as a mechanism to protect against cancer. At the same time, selection favours long telomeres as a protective mechanism against DNA damage and replicative senescence. The relative importance of these two selective forces will depend on underlying intrinsic mortality and risk of cancer, both of which are size-dependent. Results from this model suggest that a cost-benefit model for the evolution of telomere length could explain phylogenetic patterns observed within the Class Mammalia. In addition, the model suggests a general conceptual framework to think about the role that body size plays in the evolution of tumour suppressor mechanisms.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335371, year = {2018}, author = {Wilbourn, RV and Moatt, JP and Froy, H and Walling, CA and Nussey, DH and Boonekamp, JJ}, title = {The relationship between telomere length and mortality risk in non-model vertebrate systems: a meta-analysis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335371}, issn = {1471-2970}, support = {BB/H021868/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L020769/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J01446X/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Age Factors ; Animals ; Birds/genetics/*physiology ; Longevity/*physiology ; Models, Statistical ; Mortality ; Odds Ratio ; Regression Analysis ; Risk Factors ; Sex Factors ; Telomere/genetics/*physiology ; *Telomere Shortening ; }, abstract = {Telomere length (TL) has become a biomarker of increasing interest within ecology and evolutionary biology, and has been found to predict subsequent survival in some recent avian studies but not others. Here, we undertake the first formal meta-analysis to test whether there is an overall association between TL and subsequent mortality risk in vertebrates other than humans and model laboratory rodents. We identified 27 suitable studies and obtained standardized estimates of the hazard ratio associated with TL from each. We performed a meta-analysis on these estimates and found an overall significant negative association implying that short telomeres are associated with increased mortality risk, which was robust to evident publication bias. While we found that heterogeneity in the hazard ratios was not explained by sex, follow-up period, maximum lifespan or the age group of the study animals, the TL-mortality risk association was stronger in studies using qPCR compared to terminal restriction fragment methodologies. Our results provide support for a consistent association between short telomeres and increased mortality risk in birds, but also highlight the need for more research into non-avian vertebrates and the reasons why different telomere measurement methods may yield different results.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335370, year = {2018}, author = {Monaghan, P and Ozanne, SE}, title = {Somatic growth and telomere dynamics in vertebrates: relationships, mechanisms and consequences.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335370}, issn = {1471-2970}, mesh = {Adult Stem Cells/*physiology ; Animals ; Birds/growth & development ; Body Size ; Humans ; Longevity ; Mice ; Oxidative Stress ; Rats ; Telomere/*physiology ; Telomere Shortening/*physiology ; }, abstract = {Much telomere loss takes place during the period of most rapid growth when cell proliferation and potentially energy expenditure are high. Fast growth is linked to reduced longevity. Therefore, the effects of somatic cell proliferation on telomere loss and cell senescence might play a significant role in driving the growth-lifespan trade-off. While different species will have evolved a growth strategy that maximizes lifetime fitness, environmental conditions encountered during periods of growth will influence individual optima. In this review, we first discuss the routes by which altered cellular conditions could influence telomere loss in vertebrates, with a focus on oxidative stress in both in vitro and in vivo studies. We discuss the relationship between body growth and telomere length, and evaluate the empirical evidence that this relationship is generally negative. We further discuss the potentially conflicting hypotheses that arise when other factors are taken into account, and the further work that needs to be undertaken to disentangle confounding variables.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335369, year = {2018}, author = {Tricola, GM and Simons, MJP and Atema, E and Boughton, RK and Brown, JL and Dearborn, DC and Divoky, G and Eimes, JA and Huntington, CE and Kitaysky, AS and Juola, FA and Lank, DB and Litwa, HP and Mulder, EGA and Nisbet, ICT and Okanoya, K and Safran, RJ and Schoech, SJ and Schreiber, EA and Thompson, PM and Verhulst, S and Wheelwright, NT and Winkler, DW and Young, R and Vleck, CM and Haussmann, MF}, title = {The rate of telomere loss is related to maximum lifespan in birds.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335369}, issn = {1471-2970}, support = {WT107400MA//Wellcome Trust/United Kingdom ; }, mesh = {Aging/genetics/*physiology ; Animals ; Biological Variation, Population ; Birds/genetics/*physiology ; Cellular Senescence ; Cross-Sectional Studies ; Female ; Longevity/genetics/*physiology ; Male ; Phylogeny ; Telomere/genetics/*physiology ; Telomere Shortening/genetics/*physiology ; }, abstract = {Telomeres are highly conserved regions of DNA that protect the ends of linear chromosomes. The loss of telomeres can signal an irreversible change to a cell's state, including cellular senescence. Senescent cells no longer divide and can damage nearby healthy cells, thus potentially placing them at the crossroads of cancer and ageing. While the epidemiology, cellular and molecular biology of telomeres are well studied, a newer field exploring telomere biology in the context of ecology and evolution is just emerging. With work to date focusing on how telomere shortening relates to individual mortality, less is known about how telomeres relate to ageing rates across species. Here, we investigated telomere length in cross-sectional samples from 19 bird species to determine how rates of telomere loss relate to interspecific variation in maximum lifespan. We found that bird species with longer lifespans lose fewer telomeric repeats each year compared with species with shorter lifespans. In addition, phylogenetic analysis revealed that the rate of telomere loss is evolutionarily conserved within bird families. This suggests that the physiological causes of telomere shortening, or the ability to maintain telomeres, are features that may be responsible for, or co-evolved with, different lifespans observed across species.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335368, year = {2018}, author = {Harrington, L and Pucci, F}, title = {In medio stat virtus: unanticipated consequences of telomere dysequilibrium.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335368}, issn = {1471-2970}, support = {//Wellcome Trust/United Kingdom ; 086580//Wellcome Trust/United Kingdom ; 084637//Wellcome Trust/United Kingdom ; 133573//Canadian Institutes of Health Research/International ; 148936//Canadian Institutes of Health Research/International ; }, mesh = {Animals ; Cell Differentiation/genetics/*physiology ; Cellular Senescence/genetics/*physiology ; DNA Methylation/genetics/*physiology ; Epigenesis, Genetic ; Histones/metabolism ; Humans ; Primary Cell Culture ; Protein Processing, Post-Translational/genetics/*physiology ; Stem Cells ; Telomere/genetics/*physiology ; *Telomere Homeostasis ; Telomere-Binding Proteins/metabolism ; }, abstract = {The integrity of chromosome ends, or telomeres, depends on myriad processes that must balance the need to compact and protect the telomeric, G-rich DNA from detection as a double-stranded DNA break, and yet still permit access to enzymes that process, replicate and maintain a sufficient reserve of telomeric DNA. When unable to maintain this equilibrium, erosion of telomeres leads to perturbations at or near the telomeres themselves, including loss of binding by the telomere protective complex, shelterin, and alterations in transcription and post-translational modifications of histones. Although the catastrophic consequences of full telomere de-protection are well described, recent evidence points to other, less obvious perturbations that arise when telomere length equilibrium is altered. For example, critically short telomeres also perturb DNA methylation and histone post-translational modifications at distal sites throughout the genome. In murine stem cells for example, this dysregulated chromatin leads to inappropriate suppression of pluripotency regulator factors such as Nanog This review summarizes these recent findings, with an emphasis on how these genome-wide, telomere-induced perturbations can have profound consequences on cell function and fate.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335367, year = {2018}, author = {Tian, X and Doerig, K and Park, R and Can Ran Qin, A and Hwang, C and Neary, A and Gilbert, M and Seluanov, A and Gorbunova, V}, title = {Evolution of telomere maintenance and tumour suppressor mechanisms across mammals.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335367}, issn = {1471-2970}, support = {P01 AG047200/AG/NIA NIH HHS/United States ; R03 AG052365/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Carcinogenesis/*genetics ; Cellular Senescence/genetics ; *Evolution, Molecular ; Fibroblasts/cytology ; Genes, Retinoblastoma/genetics ; Genes, p53/genetics ; Genes, ras/genetics ; Humans ; Mice, Nude ; Primary Cell Culture ; Rodentia/*genetics ; Skin/cytology ; Telomerase/metabolism ; Telomere/*metabolism ; *Telomere Homeostasis ; Xenograft Model Antitumor Assays ; }, abstract = {Mammalian species differ dramatically in telomere biology. Species larger than 5-10 kg repress somatic telomerase activity and have shorter telomeres, leading to replicative senescence. It has been proposed that evolution of replicative senescence in large-bodied species is an anti-tumour mechanism counteracting increased risk of cancer due to increased cell numbers. By contrast, small-bodied species express high telomerase activity and have longer telomeres. To counteract cancer risk due to longer lifespan, long-lived small-bodied species evolved additional telomere-independent tumour suppressor mechanisms. Here, we tested the connection between telomere biology and tumorigenesis by analysing the propensity of fibroblasts from 18 rodent species to form tumours. We found a negative correlation between species lifespan and anchorage-independent growth. Small-bodied species required inactivation of Rb and/or p53 and expression of oncogenic H-Ras to form tumours. Large-bodied species displayed a continuum of phenotypes requiring additional genetic 'hits' for malignant transformation. Based on these data we refine the model of the evolution of tumour suppressor mechanisms and telomeres. We propose that two different strategies evolved in small and large species because small-bodied species cannot tolerate small tumours that form prior to activation of the telomere barrier, and must instead use telomere-independent strategies that act earlier, at the hyperplasia stage.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335366, year = {2018}, author = {Eisenberg, DTA and Kuzawa, CW}, title = {The paternal age at conception effect on offspring telomere length: mechanistic, comparative and adaptive perspectives.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335366}, issn = {1471-2970}, mesh = {Adaptation, Physiological/*physiology ; Aging ; Animals ; Child ; Fertilization/*physiology ; Humans ; Male ; *Paternal Age ; Spermatozoa/metabolism ; Telomerase/metabolism ; Telomere/*metabolism ; *Telomere Homeostasis ; }, abstract = {Telomeres are repeating DNA found at the ends of chromosomes that, in the absence of restorative processes, shorten with cell replications and are implicated as a cause of senescence. It appears that sperm telomere length (TL) increases with age in humans, and as a result offspring of older fathers inherit longer telomeres. We review possible mechanisms underlying this paternal age at conception (PAC) effect on TL, including sperm telomere extension due to telomerase activity, age-dependent changes in the spermatogonial stem cell population (possibly driven by 'selfish' spermatogonia) and non-causal confounding. In contrast to the lengthening of TL with PAC, higher maternal age at conception appears to predict shorter offspring TL in humans. We review evidence for heterogeneity across species in the PAC effect on TL, which could relate to differences in statistical power, sperm production rates or testicular telomerase activity. Finally, we review the hypothesis that the PAC effect on TL may allow a gradual multi-generational adaptive calibration of maintenance effort, and reproductive lifespan, to local demographic conditions: descendants of males who reproduced at a later age are likely to find themselves in an environment where increased maintenance effort, allowing later reproduction, represents a fitness improving resource allocation.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335365, year = {2018}, author = {de Punder, K and Heim, C and Przesdzing, I and Wadhwa, PD and Entringer, S}, title = {Characterization in humans of in vitro leucocyte maximal telomerase activity capacity and association with stress.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335365}, issn = {1471-2970}, support = {R01 HD065825/HD/NICHD NIH HHS/United States ; R01 HD060628/HD/NICHD NIH HHS/United States ; R01 AG050455/AG/NIA NIH HHS/United States ; }, mesh = {Adrenocorticotropic Hormone/blood ; Adult ; Biological Variation, Population ; Body Mass Index ; Female ; Humans ; Hydrocortisone/blood ; Leukocytes/*drug effects ; Male ; Mitogens/pharmacology ; Phytohemagglutinins/pharmacology ; Saliva/drug effects ; *Stress, Psychological ; Surveys and Questionnaires ; Telomerase/*metabolism ; Telomere/metabolism ; }, abstract = {The goal of this study was to develop and validate a measure of maximal telomerase activity capacity (mTAC) for use in human studies of telomere biology, and to determine its association with measures of stress and stress responsivity. The study was conducted in a population of 28 healthy young women and men who were assessed serially across two separate days, at multiple time points, and in response to a standardized laboratory stressor. Venous blood was collected at each of these multiple assessments, and an in vitro mitogen challenge (phytohaemagglutinin supplemented with interleukin-2) was used to stimulate telomerase activity in leucocytes. After first establishing the optimal post-stimulation time course to characterize mTAC, we determined the within-subject stability and the between-subject variability of mTAC. The major findings of our study are as follows: (i) the optimal time point to quantify human leucocyte mTAC appears to be at 72 h after mitogen stimulation; (ii) mTAC exhibits substantial within-subject stability (correlations were in the range of r 0.68-0.82) and between-subject variability, with a high intra-class coefficient (0.70), indicating greater between-subject relative to within-subject variability; (iii) mTAC is not influenced by situational factors including time of day, cortisol, acute stress exposure and immune cell distribution in the pre-stimulation blood sample; and (iv) a significant proportion of the between-subject variability in mTAC is associated with measures of stress and stress responsivity (mTAC is lower in subjects reporting higher levels of perceived (chronic) stress and exhibiting higher psychophysiological stress reactivity). Based collectively on these findings, it appears that mTAC, as proposed and operationalized, empirically meets the key criteria to represent a potentially useful individual difference measure of telomerase activity capacity of human leucocytes.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335364, year = {2018}, author = {Criscuolo, F and Smith, S and Zahn, S and Heidinger, BJ and Haussmann, MF}, title = {Experimental manipulation of telomere length: does it reveal a corner-stone role for telomerase in the natural variability of individual fitness?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335364}, issn = {1471-2970}, mesh = {*Animal Experimentation ; Animals ; Biological Evolution ; *Biological Variation, Individual ; Environment ; *Genetic Fitness ; Humans ; *Physical Fitness ; Telomerase/genetics/*physiology ; Telomere/genetics/*physiology ; *Telomere Homeostasis ; }, abstract = {Telomeres, the non-coding ends of linear chromosomes, are thought to be an important mechanism of individual variability in performance. Research suggests that longer telomeres are indicative of better health and increased fitness; however, many of these data are correlational and whether these effects are causal are poorly understood. Experimental tests are emerging in medical and laboratory-based studies, but these types of experiments are rare in natural populations, which precludes conclusions at an evolutionary level. At the crossroads between telomere length and fitness is telomerase, an enzyme that can lengthen telomeres. Experimental modulation of telomerase activity is a powerful tool to manipulate telomere length, and to look at the covariation of telomerase, telomeres and individual life-history traits. Here, we review studies that manipulate telomerase activity in laboratory conditions and emphasize the associated physiological and fitness consequences. We then discuss how telomerase's impact on ageing may go beyond telomere maintenance. Based on this overview, we then propose several research avenues for future studies to explore how individual variability in health, reproduction and survival may have coevolved with different patterns of telomerase activity and expression. Such knowledge is of prime importance to fully understand the role that telomere dynamics play in the evolution of animal ageing.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335363, year = {2018}, author = {Bateson, M and Nettle, D}, title = {Why are there associations between telomere length and behaviour?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1741}, pages = {}, pmid = {29335363}, issn = {1471-2970}, mesh = {Animals ; Behavior/*physiology ; Birds ; Humans ; Leukocytes ; Longitudinal Studies ; Models, Theoretical ; Smoking ; Telomere/genetics/*physiology ; Telomere Shortening/genetics/*physiology ; }, abstract = {Individual differences in telomere length are associated with individual differences in behaviour in humans and birds. Within the human epidemiological literature this association is assumed to result from specific behaviour patterns causing changes in telomere dynamics. We argue that selective adoption-the hypothesis that individuals with short telomeres are more likely to adopt specific behaviours-is an alternative worthy of consideration. Selective adoption could occur either because telomere length directly affects behaviour or because behaviour and telomere length are both affected by a third variable, such as exposure to early-life adversity. We present differential predictions of the causation and selective adoption hypotheses and describe how these could be tested with longitudinal data on telomere length. Crucially, if behaviour is causal then it should be associated with differential rates of telomere attrition. Using smoking behaviour as an example, we show that the evidence that smoking accelerates the rate of telomere attrition within individuals is currently weak. We conclude that the selective adoption hypothesis for the association between behaviour and telomere length is both mechanistically plausible and, if anything, more compatible with existing empirical evidence than the hypothesis that behaviour is causal.This article is part of the theme issue 'Understanding diversity in telomere dynamics'.}, } @article {pmid29335029, year = {2018}, author = {Tedla, M and Gebreselassie, M}, title = {Estimating the proportion of clinically diagnosed infectious and non-infectious animal diseases in Ganta Afeshum woreda, Eastern Tigray zone, Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {29}, pmid = {29335029}, issn = {1756-0500}, mesh = {Animals ; Cattle ; Cattle Diseases/diagnosis/*epidemiology ; Cross-Sectional Studies ; Ethiopia/epidemiology ; Female ; Goat Diseases/diagnosis/*epidemiology ; Goats ; Horse Diseases/diagnosis/*epidemiology ; Horses ; Male ; Sheep ; Sheep Diseases/diagnosis/*epidemiology ; }, abstract = {OBJECTIVE: This study was performed with the objective of identifying the proportion of emerging and endemic livestock diseases using cross sectional survey.

RESULT: A total of 285 clinically diseased animals were presented to a veterinary clinic and diagnosed tentatively based on history, clinical sign, and simple laboratory diagnostics and from the study, actinomycosis (15.83%), mastitis (15%), tick infestation (10%), respiratory diseases (9.16%) and gastro intestinal parasitism (9.16%) were confirmed with higher proportion in large animals. Pasteurollosis (38, 31%), contagious ecthyma (12, 10%), tick infestation (9, 0%), mite infestation (9, 10%), sheep and goat pox (9, 10%), and gastrointestinal parasitism (9, 17%) were frequently encountered diseases in sheep and goat respectively. In equids, back sore, epizootic lymphangitis and lameness accounted a proportion of 22.95, 21.31, and 13.11% respectively. In conclusion, result of the present study showed that the proportion of livestock disease is high, and it affects the socioeconomic status of the local community in the study area as a result of mortality and production loss.}, } @article {pmid29335027, year = {2018}, author = {Tipton, L and Müller, CL and Kurtz, ZD and Huang, L and Kleerup, E and Morris, A and Bonneau, R and Ghedin, E}, title = {Fungi stabilize connectivity in the lung and skin microbial ecosystems.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {12}, pmid = {29335027}, issn = {2049-2618}, support = {K24 HL123342/HL/NHLBI NIH HHS/United States ; PN2 EY016586/EY/NEI NIH HHS/United States ; U01 HL098962/HL/NHLBI NIH HHS/United States ; GM32877-21/22//National Institutes of Health (US)/International ; EY016586-06/NH/NIH HHS/United States ; U54 CA143907/CA/NCI NIH HHS/United States ; K24 HL123342/NH/NIH HHS/United States ; PN2-EY016586/NH/NIH HHS/United States ; U01HL098962//National Institutes of Health (US)/International ; IU54CA143907-01/NH/NIH HHS/United States ; K24 HL087713/HL/NHLBI NIH HHS/United States ; IOS-1126971//National Science Foundation/International ; R01 HL090339/HL/NHLBI NIH HHS/United States ; R01 GM032877/GM/NIGMS NIH HHS/United States ; PN1 EY016586/EY/NEI NIH HHS/United States ; R01HL090339/NH/NIH HHS/United States ; }, mesh = {Adult ; Bacteria/*classification/genetics/isolation & purification ; Computational Biology/*methods ; Female ; Fungi/*classification/genetics/isolation & purification ; Humans ; Lung/*microbiology ; Male ; Microbial Consortia ; Middle Aged ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Skin/*microbiology ; }, abstract = {BACKGROUND: No microbe exists in isolation, and few live in environments with only members of their own kingdom or domain. As microbiome studies become increasingly more interested in the interactions between microbes than in cataloging which microbes are present, the variety of microbes in the community should be considered. However, the majority of ecological interaction networks for microbiomes built to date have included only bacteria. Joint association inference across multiple domains of life, e.g., fungal communities (the mycobiome) and bacterial communities, has remained largely elusive.

RESULTS: Here, we present a novel extension of the SParse InversE Covariance estimation for Ecological ASsociation Inference (SPIEC-EASI) framework that allows statistical inference of cross-domain associations from targeted amplicon sequencing data. For human lung and skin micro- and mycobiomes, we show that cross-domain networks exhibit higher connectivity, increased network stability, and similar topological re-organization patterns compared to single-domain networks. We also validate in vitro a small number of cross-domain interactions predicted by the skin association network.

CONCLUSIONS: For the human lung and skin micro- and mycobiomes, our findings suggest that fungi play a stabilizing role in ecological network organization. Our study suggests that computational efforts to infer association networks that include all forms of microbial life, paired with large-scale culture-based association validation experiments, will help formulate concrete hypotheses about the underlying biological mechanisms of species interactions and, ultimately, help understand microbial communities as a whole.}, } @article {pmid29335025, year = {2018}, author = {Basode, VK and Abdulhaq, A and Alamoudi, MUA and Tohari, HM and Quhal, WA and Madkhali, AM and Hobani, YH and Hershan, AA}, title = {Prevalence of a carbapenem-resistance gene (KPC), vancomycin-resistance genes (van A/B) and a methicillin-resistance gene (mecA) in hospital and municipal sewage in a southwestern province of Saudi Arabia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {30}, pmid = {29335025}, issn = {1756-0500}, support = {FS3-053//under the program future scientist 3, Deanship of Scientific Affairs and Research, Jazan University, Jazan, Saudi Arabia/ ; }, mesh = {Animals ; Bacterial Proteins/genetics ; Carbapenems/pharmacology ; Carbon-Oxygen Ligases/genetics ; Gram-Negative Bacteria/*genetics ; Gram-Positive Bacteria/*genetics ; Hospitals ; Humans ; Methicillin Resistance/genetics ; Prevalence ; Saudi Arabia ; Sewage/*microbiology ; Vancomycin Resistance/*genetics ; beta-Lactam Resistance/*genetics ; }, abstract = {OBJECTIVE: According to the World Health Organization, the increasing antibiotic resistance of pathogens is one of the most important threats to human health. Prevalence of a carbapenem-resistance gene (KPC), vancomycin-resistance genes (van A/B) and a methicillin-resistance gene (mecA) in hospital and municipal sewages will be potential threat to public health.

RESULTS: Vancomycin-resistance genes were detected in the sewage of community tank-II, sewage tank of the tertiary and general hospital. Carbapenem-resistance gene was detected in sewage of community tank-II and sewage from tertiary hospital. Methicillin-resistance gene was detected in sewage of community tank-II, sewage from a fish market sewage tank and sewage from an animal slaughter house sewage tank. The detection of a KPC, van A/B and a mecA in sewages will help further the process to take the appropriate measures to prevent the spread of such bacteria in the environment.}, } @article {pmid29335009, year = {2018}, author = {Ratnayake, GM and Weerathunga, PN and Ruwanpura, LP and Wickramasinghe, A and Katulanda, P}, title = {Isolated follicle stimulated hormone deficiency in male: case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {24}, pmid = {29335009}, issn = {1756-0500}, mesh = {Adult ; Azoospermia/*diagnosis/etiology ; Follicle Stimulating Hormone/*deficiency ; Humans ; Male ; Oligospermia/complications/*diagnosis/drug therapy ; }, abstract = {BACKGROUND: Recent rapid advances in assisted reproductive health technologies enables couples with subfertility to conceive through various intervention. Majority of treatment modalities target the female partner. However it is important to identify and treat male factor subfertility right at the outset. We report a case of isolated follicle stimulating hormone deficiency resulting in azoospermia and primary subfertility.

CASE PRESENTATION: A 28 year otherwise healthy male presented with primary subfertility with a healthy female counterpart. He was found to have non obstructive azoospermia with low seminal fluid volume. He had normal external genitalia and potency with increased libido. Further evaluation revealed an isolated deficiency of follicle stimulating hormone with elevated testosterone levels. His luteinizing hormone and prolactin levels were normal. Contrast enhanced CT scan of chest, abdomen and pelvis and MRI scan of the pituitary fossa were normal too.

CONCLUSION: In the era of modern reproductive technology it is important to further evaluate males with non-obstructive azoospermia to detect underlying gonadotropin deficiency.}, } @article {pmid29335008, year = {2018}, author = {Douglas, GM and Hansen, R and Jones, CMA and Dunn, KA and Comeau, AM and Bielawski, JP and Tayler, R and El-Omar, EM and Russell, RK and Hold, GL and Langille, MGI and Van Limbergen, J}, title = {Multi-omics differentially classify disease state and treatment outcome in pediatric Crohn's disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {13}, pmid = {29335008}, issn = {2049-2618}, support = {CAF/08/01//Clinical Academic Fellowship from the Chief Scientist Office (Scotland)/International ; }, mesh = {Adolescent ; Child ; Child, Preschool ; Crohn Disease/*genetics/microbiology ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Dysbiosis/*complications ; Feces/microbiology ; Female ; Genetic Predisposition to Disease ; *Genetic Variation ; Humans ; Machine Learning ; Male ; Metagenomics/*methods ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {BACKGROUND: Crohn's disease (CD) has an unclear etiology, but there is growing evidence of a direct link with a dysbiotic microbiome. Many gut microbes have previously been associated with CD, but these have mainly been confounded with patients' ongoing treatments. Additionally, most analyses of CD patients' microbiomes have focused on microbes in stool samples, which yield different insights than profiling biopsy samples.

RESULTS: We sequenced the 16S rRNA gene (16S) and carried out shotgun metagenomics (MGS) from the intestinal biopsies of 20 treatment-naïve CD and 20 control pediatric patients. We identified the abundances of microbial taxa and inferred functional categories within each dataset. We also identified known human genetic variants from the MGS data. We then used a machine learning approach to determine the classification accuracy when these datasets, collapsed to different hierarchical groupings, were used independently to classify patients by disease state and by CD patients' response to treatment. We found that 16S-identified microbes could classify patients with higher accuracy in both cases. Based on follow-ups with these patients, we identified which microbes and functions were best for predicting disease state and response to treatment, including several previously identified markers. By combining the top features from all significant models into a single model, we could compare the relative importance of these predictive features. We found that 16S-identified microbes are the best predictors of CD state whereas MGS-identified markers perform best for classifying treatment response.

CONCLUSIONS: We demonstrate for the first time that useful predictors of CD treatment response can be produced from shotgun MGS sequencing of biopsy samples despite the complications related to large proportions of host DNA. The top predictive features that we identified in this study could be useful for building an improved classifier for CD and treatment response based on sufferers' microbiome in the future. The BISCUIT project is funded by a Clinical Academic Fellowship from the Chief Scientist Office (Scotland)-CAF/08/01.}, } @article {pmid29335005, year = {2018}, author = {Lanza, VF and Baquero, F and Martínez, JL and Ramos-Ruíz, R and González-Zorn, B and Andremont, A and Sánchez-Valenzuela, A and Ehrlich, SD and Kennedy, S and Ruppé, E and van Schaik, W and Willems, RJ and de la Cruz, F and Coque, TM}, title = {In-depth resistome analysis by targeted metagenomics.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {11}, pmid = {29335005}, issn = {2049-2618}, support = {282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; 282004//EVOTARFP7-HEALTH/International ; JPIW2013-089-C02-01//JPI WATER STARE/International ; BIO2014-54507-R//Ministry of Economy and Competitiveness of Spa/International ; PLASWIRES-612146/FP7-ICT- 2013-10//Ministry of Economy and Competitiveness of Spain/International ; BFU2014-55534-C2-1-P//Ministry of Economy and Competitiveness of Spain/International ; BIO2014-54507-R//Spanish R&D National Plan 2012-2019/International ; PI15-0512//Spanish R&D National Plan 2012-2019/International ; PI15-00818//Spanish R&D National Plan 2012-2019/International ; BFU2014-55534- C2-1-P//Spanish R&D National Plan 2012-2019/International ; CB06/02/0053//CIBER in Epidemiology and Public Health, CIBERESP/International ; RD12/0015//Spanish Network for Research on Infectious Diseases (REIPI)/International ; PROMPT-S2010/BMD2414//Regional Government of Madrid/International ; ANR-11-DPBS-0001//Metagenopolis grant/International ; }, mesh = {Animals ; Computational Biology/*methods ; DNA Probes/genetics ; *Drug Resistance, Microbial ; Feces ; Genes, Bacterial ; Humans ; Metagenomics/*methods ; Swine ; }, abstract = {BACKGROUND: Antimicrobial resistance is a major global health challenge. Metagenomics allows analyzing the presence and dynamics of "resistomes" (the ensemble of genes encoding antimicrobial resistance in a given microbiome) in disparate microbial ecosystems. However, the low sensitivity and specificity of available metagenomic methods preclude the detection of minority populations (often present below their detection threshold) and/or the identification of allelic variants that differ in the resulting phenotype. Here, we describe a novel strategy that combines targeted metagenomics using last generation in-solution capture platforms, with novel bioinformatics tools to establish a standardized framework that allows both quantitative and qualitative analyses of resistomes.

METHODS: We developed ResCap, a targeted sequence capture platform based on SeqCapEZ (NimbleGene) technology, which includes probes for 8667 canonical resistance genes (7963 antibiotic resistance genes and 704 genes conferring resistance to metals or biocides), and 2517 relaxase genes (plasmid markers) and 78,600 genes homologous to the previous identified targets (47,806 for antibiotics and 30,794 for biocides or metals). Its performance was compared with metagenomic shotgun sequencing (MSS) for 17 fecal samples (9 humans, 8 swine). ResCap significantly improves MSS to detect "gene abundance" (from 2.0 to 83.2%) and "gene diversity" (26 versus 14.9 genes unequivocally detected per sample per million of reads; the number of reads unequivocally mapped increasing up to 300-fold by using ResCap), which were calculated using novel bioinformatic tools. ResCap also facilitated the analysis of novel genes potentially involved in the resistance to antibiotics, metals, biocides, or any combination thereof.

CONCLUSIONS: ResCap, the first targeted sequence capture, specifically developed to analyze resistomes, greatly enhances the sensitivity and specificity of available metagenomic methods and offers the possibility to analyze genes related to the selection and transfer of antimicrobial resistance (biocides, heavy metals, plasmids). The model opens the possibility to study other complex microbial systems in which minority populations play a relevant role.}, } @article {pmid29335004, year = {2018}, author = {Melese, A and Zeleke, B}, title = {Factors associated with poor treatment outcome of tuberculosis in Debre Tabor, northwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {25}, pmid = {29335004}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Aged ; Antitubercular Agents/administration & dosage/*pharmacology ; Ethiopia ; Female ; Humans ; Male ; Middle Aged ; *Outcome Assessment (Health Care) ; Retrospective Studies ; Tuberculosis/*drug therapy ; Young Adult ; }, abstract = {OBJECTIVE: Directly observed treatment short course has been implemented as part of the national tuberculosis control program in Ethiopia. The strategy, as evidenced by different studies, has improved the survival and treatment success rate of tuberculosis patients. However, some patients failed to complete their treatments and the factors for this failure were not assessed in the study area. We, therefore sought to identify factors associated with poor treatment outcome of tuberculosis in Debre Tabor, northwest Ethiopia.

RESULTS: We included 303 patients (173 males, 130 females) with mean age of 34.9 years in the study and 39 (12.9%) patients were with poor treatment outcome over the period of 5 years (2008-2013). Being male, urban residency, positive and unknown smear result at the 2nd month of treatment and patients in the age of 35-44 years were more likely to have poor treatment outcomes than their counterparts. Patients in the new treatment category were less likely to have poor treatment outcome compared to the retreated cases. Further studies are recommended to explore the association of poor treatment outcome with other important factors which are not investigated by this study.}, } @article {pmid29335003, year = {2018}, author = {Asgedom, SW and Atey, TM and Desse, TA}, title = {Antihypertensive medication adherence and associated factors among adult hypertensive patients at Jimma University Specialized Hospital, southwest Ethiopia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {27}, pmid = {29335003}, issn = {1756-0500}, mesh = {Adult ; Aged ; Antihypertensive Agents/*administration & dosage ; Cross-Sectional Studies ; Ethiopia ; Female ; Hospitals, University/statistics & numerical data ; Humans ; Hypertension/*drug therapy ; Male ; Medication Adherence/*statistics & numerical data ; Middle Aged ; }, abstract = {BACKGROUND: Adherence to antihypertensive medications is a key component to control blood pressure levels. Poor adherence to these medications leads to the development of hypertensive complications and increase risk of cardiovascular events which in turn reduces the ultimate clinical outcome. The purpose of this study was to assess antihypertensive medication adherence and associated factors among adult hypertensive patients. A hospital-based cross-sectional study among adult hypertensive patients was conducted at hypertensive follow-up clinic of Jimma University Specialized Hospital from March 4, 2015 to April 3, 2015. A simple random sampling technique was used to select the study participants from the study population. The study patients were interviewed and their medical charts were reviewed using a pretested structured questionnaire. Adherence was assessed using Morisky Medication Adherence Scale-8 (MMAS-8) and MMAS-8 score less than 6 was considered as non-adherent and MMAS-8 score was ≥ 6 was declared as adherence. Factors associated with adherence were identified using binary and multivariate logistic regression analysis. Crude odds ratio, adjusted odds ratio (AOR) and 95% confidence interval of the odds ratio were calculated using SPSS version 21. Variables with p-value less than 0.05 were assumed as statistically significant factors.

RESULTS: Among 280 hypertensive patients, 61.8% of the study participants were found to be adherent. More than half (53.2%) of the participants were males and the mean age of the participants was 55.0 ± 12.7 years. Co-morbidity (AOR = 0.083, 95% CI = 0.033-0.207, p < 0.001), alcohol intake (AOR = 0.011, 95% CI = 0.002-0.079, p < 0.001), getting medications freely (AOR = 0.020, 95% CI = 0.003-0.117, p < 0.001), and combination of antihypertensive medications (AOR = 0.32, 95% CI = 0.144-0.712, p < 0.005) were inversely associated with antihypertensive medication adherence.

CONCLUSION: The adherence level to the prescribed antihypertensive medications was found to be sub-optimal according to the MMAS-8, and influenced by co morbidity, alcohol intake, self-purchasing of the medications and combination of antihypertensive medications.}, } @article {pmid29334998, year = {2018}, author = {Morter, R and Adetifa, I and Antonio, M and Touray, F and de Jong, BC and Gower, CM and Gehre, F}, title = {Examining human paragonimiasis as a differential diagnosis to tuberculosis in The Gambia.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {31}, pmid = {29334998}, issn = {1756-0500}, support = {311725//European Research Council/International ; GMB-T-MRC//Global Fund to Fight AIDS, Tuberculosis and Malaria/ ; }, mesh = {Adolescent ; Adult ; Aged ; Child ; Diagnosis, Differential ; Female ; Gambia/epidemiology ; Humans ; Male ; Middle Aged ; Paragonimiasis/*diagnosis/epidemiology ; Polymerase Chain Reaction ; Tuberculosis/*diagnosis/epidemiology ; Young Adult ; }, abstract = {OBJECTIVE: Paragonimiasis is a foodborne trematode infection of the lungs caused by Paragonimus spp., presenting clinically with similar symptoms to active tuberculosis (TB). Worldwide, an estimated 20.7 million people are infected with paragonimiasis, but relatively little epidemiological data exists for Africa. Given a recently reported case, we sought to establish whether paragonimiasis should be considered as an important differential diagnosis for human TB in The Gambia, West Africa.

RESULTS: We developed a novel PCR-based diagnostic test for Paragonimus species known to be found in West Africa, which we used to examine archived TB negative sputum samples from a cross-sectional study of volunteers with tuberculosis-like symptoms from communities in the Western coastal region of The Gambia. Based on a "zero patient" design for detection of rare diseases, 300 anonymised AFB smear negative sputum samples, randomly selected from 25 villages, were screened for active paragonimiasis by molecular detection of Paragonimus spp. DNA. No parasite DNA was found in any of the sputa of our patient group. Despite the recent case report, we found no evidence of active paragonimiasis infection masking as TB in the Western region of The Gambia.}, } @article {pmid29334997, year = {2018}, author = {Hortensius, J and Kleefstra, N and Landman, GWD and Houweling, BT and Groenier, KH and van der Bijl, JJ and Bilo, H}, title = {Effects of three frequencies of self-monitored blood glucose on HbA1c and quality of life in patients with type 2 diabetes with once daily insulin and stable control: a randomized trial.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {26}, pmid = {29334997}, issn = {1756-0500}, mesh = {Aged ; Blood Glucose Self-Monitoring/*methods ; Diabetes Mellitus, Type 2/*blood/*drug therapy ; Female ; Glycated Hemoglobin A/*analysis ; Humans ; Hypoglycemic Agents/administration & dosage/*pharmacology ; Insulin/administration & dosage/*pharmacology ; Male ; Middle Aged ; *Outcome Assessment (Health Care) ; *Quality of Life ; }, abstract = {OBJECTIVE: The optimal frequency of self-monitoring of blood glucose (SMBG) in patients with type 2 diabetes (T2DM) with stable glycemic control is unknown. This study investigated effects of 3 frequencies of SMBG on glycemic control and quality of life after 9 months in patients using one long-acting insulin injection a day. In an open-label, multi-center, primary-care, parallel (1:1:1) randomized trial in the Netherlands including patients with T2DM, HbA1c ≤ 58 mmol/mol (≤ 7.5%), stable glycemic control, treated with one insulin injection daily, three frequencies of 4-point glucose measurements (before meals and bedtime) were weekly (n = 22), every 2 weeks (n = 16) and monthly (n = 20) were compared.

RESULTS: A total of 58 patients with T2DM were included by 38 general practitioners, which was lower then anticipated. There were no significant between group differences in HbA1c (mmol/mol); group C compared to A and B; - 2.7 (95% CI - 6.4, 1.0) and - 1.0 (95% CI - 4.9, 3.0) and quality of life. Baring in mind the lower than anticipated inclusion rate, there were no significant differences in HbA1c and quality of life between three different frequencies of SMBG in patients with stable glycemic control using one long-acting insulin injection. Trial registration NCT01460459, registered 10-2011, recruitment between 05-2011 and 12-2011.}, } @article {pmid29334993, year = {2018}, author = {Oliveira, MR and Schwartz, I and Costa, LS and Maia, H and Ribeiro, M and Guerreiro, LB and Acosta, A and Rocha, NS}, title = {Quality of life in mucopolysaccharidoses: construction of a specific measure using the focus group technique.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {28}, pmid = {29334993}, issn = {1756-0500}, mesh = {Adolescent ; Adult ; Brazil ; Caregivers ; Child ; Female ; Focus Groups ; Health Personnel ; Humans ; Male ; Middle Aged ; Mucopolysaccharidoses/*psychology ; Psychometrics/instrumentation/*methods ; Quality of Life/*psychology ; Young Adult ; }, abstract = {OBJECTIVE: To describe the perceptions of patients, their caregivers, and their healthcare providers to the development of a new specific instrument for assessment of the quality of life (QoL) in patients with mucopolysaccharidoses (MPS) using a qualitative focus group (FG) design. FGs were held in two Brazilian states (Rio Grande do Sul and Rio de Janeiro).

RESULTS: Three versions of the new instrument were developed, each for a different age group: children (age 8-12 years), adolescents (age 13-17), and adults (age ≥ 18). The FGs mostly confirmed the relevance of items. All FGs unanimously agreed on the facets: School, Happiness, Life Prospects, Religiosity, Pain, Continuity of Treatment, Trust in Treatment, Relationship with Family, Relationship with Healthcare Providers, Acceptance, and Meaning of Life. The overall concept of QoL (as proposed by the WHO-World Health Organization) and its facets apply to this patient population. However, other specific facets-particularly concerning clinical manifestations and the reality of the disease-were suggested, confirming the need for the development of a specific QoL instrument for MPS.}, } @article {pmid29334950, year = {2018}, author = {Pelletier, F and Coltman, DW}, title = {Will human influences on evolutionary dynamics in the wild pervade the Anthropocene?.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {7}, pmid = {29334950}, issn = {1741-7007}, abstract = {The five most pervasive anthropogenic threats to biodiversity are over-exploitation, habitat changes, climate change, invasive species, and pollution. Since all of these threats can affect intraspecific biodiversity-including genetic variation within populations-humans have the potential to induce contemporary microevolution in wild populations. We highlight recent empirical studies that have explored the effects of these anthropogenic threats to intraspecific biodiversity in the wild. We conclude that it is critical that we move towards a predictive framework that integrates a better understanding of contemporary microevolution to multiple threats to forecast the fate of natural populations in a changing world.}, } @article {pmid29334940, year = {2018}, author = {Dukowic-Schulze, S and Sundararajan, A and Mudge, J and Ramaraj, T and Farmer, AD and Wang, M and Sun, Q and Pillardy, J and Kianian, S and Retzel, EF and Pawlowski, WP and Chen, C}, title = {Correction to: The transcriptome landscape of early maize meiosis.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {12}, pmid = {29334940}, issn = {1471-2229}, abstract = {CORRECTION: Following publication of the original article [1], the authors reported that the number of genes overlaying the bar graph in Fig. 3A were incorrectly counted and inserted (i.e. including a title tile, and in inverse order). The corrected numbers are below and match with the listed genes supplied in Additional File: Table S2.}, } @article {pmid29334916, year = {2018}, author = {Liu, Y and Wu, Q and Ge, G and Han, G and Jia, Y}, title = {Influence of drought stress on afalfa yields and nutritional composition.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {13}, pmid = {29334916}, issn = {1471-2229}, support = {31360585//National Natural Science Foundation of China/International ; }, mesh = {Carbohydrates/analysis ; China ; *Droughts ; Medicago sativa/*chemistry/genetics/*physiology ; Plant Proteins/analysis ; }, abstract = {BACKGROUND: It is predicted that climate change may increase the risk of local droughts, with severe consequences for agricultural practices.

METHODS: Here we report the influence of drought on alfalfa yields and nutritional composition, based on artificially induced drought conditions during two field experiments. Two types of alfalfa cultivars were compared, Gold Queen and Suntory. The severity and timing of drought periods were varied, and the crop was harvested either early during flowering, or late at full bloom.

RESULTS: The obtained dry mass yields of Gold Queen were higher than Suntory, and the first was also more resistant to drought. Early harvest resulted in higher yields. Decreases in yields due to water shortage were observed with both cultivars, and the fraction of crude protein (CP) decreased as a result of drought stress; this fraction was higher in Gold Queen than in Suntory and higher in early harvest compared to late harvest. Severe drought late in spring had the highest effect on CP content. The fraction of fibre, split up into neutral detergent fibre (NDF) and acid detergent fibre (ADF) increased as a result of drought and was lower in early compared to late harvested plants. Suntory alfalfa produced higher fibre fractions than Gold Queen. The fraction of water-soluble carbohydrates (WSC) was least affected by drought. It was consistently higher in Gold Queen compared to Suntory alfalfa, and late harvest resulted in higher WSC content.

CONCLUSIONS: In combination, these results suggest that the nutritive value of alfalfa will likely decrease after a period of drought. These effects can be partly overcome by choosing the Gold Queen cultivar over Suntory, by targeted irrigation, in particular in late spring, and by harvesting at an earlier time.}, } @article {pmid29334902, year = {2018}, author = {Gonzalez, DO and Church, JB and Robinson, A and Connell, JP and Sopko, M and Rowland, B and Woodall, K and Larsen, CM and Davies, JP}, title = {Expression characterization of the herbicide tolerance gene Aryloxyalkanoate Dioxygenase (aad-1) controlled by seven combinations of regulatory elements.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {14}, pmid = {29334902}, issn = {1471-2229}, mesh = {Dioxygenases/*genetics/metabolism ; Gene Expression Regulation, Plant/*drug effects ; Herbicide Resistance/*genetics ; Herbicides/*pharmacology ; Plant Proteins/*genetics/metabolism ; Plants, Genetically Modified/drug effects/genetics/metabolism ; Regulatory Sequences, Nucleic Acid/*genetics ; Zea mays/drug effects/*genetics/metabolism ; }, abstract = {BACKGROUND: Availability of well characterized maize regulatory elements for gene expression in a variety of tissues and developmental stages provides effective alternatives for single and multigene transgenic concepts. We studied the expression of the herbicide tolerance gene aryloxyalkanoate dioxygenase (aad-1) driven by seven different regulatory element construct designs including the ubiquitin promoters of maize and rice, the actin promoters of melon and rice, three different versions of the Sugarcane Bacilliform Badnavirus promoters in association with other regulatory elements of gene expression.

RESULTS: Gene expression of aad-1 was characterized at the transcript and protein levels in a collection of maize tissues and developmental stages. Protein activity against its target herbicide was characterized by herbicide dosage response. Although differences in transcript and protein accumulation were observed among the different constructs tested, all events were tolerant to commercially relevant rates of quizalafop-P-ethyl compared to non-traited maize under greenhouse conditions.

DISCUSSION: The data reported demonstrate how different regulatory elements affect transcript and protein accumulation and how these molecular characteristics translate into the level of herbicide tolerance. The level of transcript detected did not reflect the amount of protein quantified in a particular tissue since protein accumulation may be influenced not only by levels of transcript produced but also by translation rate, post-translational regulation mechanisms and protein stability. The amount of AAD-1 enzyme produced with all constructs tested showed sufficient enzymatic activity to detoxify the herbicide and prevent most herbicidal damage at field-relevant levels without having a negative effect on plant health.

CONCLUSIONS: Distinctive profiles of aad-1 transcript and protein accumulation were observed when different regulatory elements were utilized in the constructs under study. The ZmUbi and the SCBV constructs showed the most consistent robust tolerance, while the melon actin construct provided the lowest level of tolerance compared to the other regulatory elements used in this study. These data provide insights into the effects of differing levels of gene expression and how these molecular characteristics translate into the level of herbicide tolerance. Furthermore, these data provide valuable information to optimize future designs of single and multiple gene constructs for maize research and crop improvement.}, } @article {pmid29334899, year = {2018}, author = {Jang, S and Lee, Y and Lee, G and Seo, J and Lee, D and Yu, Y and Chin, JH and Koh, HJ}, title = {Association between sequence variants in panicle development genes and the number of spikelets per panicle in rice.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {5}, pmid = {29334899}, issn = {1471-2156}, mesh = {DNA, Plant ; *Genetic Variation ; Haplotypes ; Inflorescence/*anatomy & histology/genetics ; Oryza/*anatomy & histology/*genetics/physiology ; Phenotype ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Balancing panicle-related traits such as panicle length and the numbers of primary and secondary branches per panicle, is key to improving the number of spikelets per panicle in rice. Identifying genetic information contributes to a broader understanding of the roles of gene and provides candidate alleles for use as DNA markers. Discovering relations between panicle-related traits and sequence variants allows opportunity for molecular application in rice breeding to improve the number of spikelets per panicle.

RESULTS: In total, 142 polymorphic sites, which constructed 58 haplotypes, were detected in coding regions of ten panicle development gene and 35 sequence variants in six genes were significantly associated with panicle-related traits. Rice cultivars were clustered according to their sequence variant profiles. One of the four resultant clusters, which contained only indica and tong-il varieties, exhibited the largest average number of favorable alleles and highest average number of spikelets per panicle, suggesting that the favorable allele combination found in this cluster was beneficial in increasing the number of spikelets per panicle.

CONCLUSIONS: Favorable alleles identified in this study can be used to develop functional markers for rice breeding programs. Furthermore, stacking several favorable alleles has the potential to substantially improve the number of spikelets per panicle in rice.}, } @article {pmid29334898, year = {2018}, author = {Jandrasits, C and Dabrowski, PW and Fuchs, S and Renard, BY}, title = {seq-seq-pan: building a computational pan-genome data structure on whole genome alignment.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {47}, pmid = {29334898}, issn = {1471-2164}, mesh = {Genomics/*methods ; Phylogeny ; Sequence Alignment/*methods ; Software ; }, abstract = {BACKGROUND: The increasing application of next generation sequencing technologies has led to the availability of thousands of reference genomes, often providing multiple genomes for the same or closely related species. The current approach to represent a species or a population with a single reference sequence and a set of variations cannot represent their full diversity and introduces bias towards the chosen reference. There is a need for the representation of multiple sequences in a composite way that is compatible with existing data sources for annotation and suitable for established sequence analysis methods. At the same time, this representation needs to be easily accessible and extendable to account for the constant change of available genomes.

RESULTS: We introduce seq-seq-pan, a framework that provides methods for adding or removing new genomes from a set of aligned genomes and uses these to construct a whole genome alignment. Throughout the sequential workflow the alignment is optimized for generating a representative linear presentation of the aligned set of genomes, that enables its usage for annotation and in downstream analyses.

CONCLUSIONS: By providing dynamic updates and optimized processing, our approach enables the usage of whole genome alignment in the field of pan-genomics. In addition, the sequential workflow can be used as a fast alternative to existing whole genome aligners for aligning closely related genomes. seq-seq-pan is freely available at https://gitlab.com/rki_bioinformatics.}, } @article {pmid29334897, year = {2018}, author = {Gupta, DK and Rühl, M and Mishra, B and Kleofas, V and Hofrichter, M and Herzog, R and Pecyna, MJ and Sharma, R and Kellner, H and Hennicke, F and Thines, M}, title = {The genome sequence of the commercially cultivated mushroom Agrocybe aegerita reveals a conserved repertoire of fruiting-related genes and a versatile suite of biopolymer-degrading enzymes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {48}, pmid = {29334897}, issn = {1471-2164}, mesh = {Agrocybe/cytology/enzymology/*genetics ; Amino Acid Sequence ; Biopolymers/metabolism ; Conserved Sequence ; Fruiting Bodies, Fungal/cytology/*genetics ; Genes, Fungal ; *Genome, Fungal ; Genomics ; Oxidoreductases/genetics ; }, abstract = {BACKGROUND: Agrocybe aegerita is an agaricomycete fungus with typical mushroom features, which is commercially cultivated for its culinary use. In nature, it is a saprotrophic or facultative pathogenic fungus causing a white-rot of hardwood in forests of warm and mild climate. The ease of cultivation and fructification on solidified media as well as its archetypal mushroom fruit body morphology render A. aegerita a well-suited model for investigating mushroom developmental biology.

RESULTS: Here, the genome of the species is reported and analysed with respect to carbohydrate active genes and genes known to play a role during fruit body formation. In terms of fruit body development, our analyses revealed a conserved repertoire of fruiting-related genes, which corresponds well to the archetypal fruit body morphology of this mushroom. For some genes involved in fruit body formation, paralogisation was observed, but not all fruit body maturation-associated genes known from other agaricomycetes seem to be conserved in the genome sequence of A. aegerita. In terms of lytic enzymes, our analyses suggest a versatile arsenal of biopolymer-degrading enzymes that likely account for the flexible life style of this species. Regarding the amount of genes encoding CAZymes relevant for lignin degradation, A. aegerita shows more similarity to white-rot fungi than to litter decomposers, including 18 genes coding for unspecific peroxygenases and three dye-decolourising peroxidase genes expanding its lignocellulolytic machinery.

CONCLUSIONS: The genome resource will be useful for developing strategies towards genetic manipulation of A. aegerita, which will subsequently allow functional genetics approaches to elucidate fundamentals of fruiting and vegetative growth including lignocellulolysis.}, } @article {pmid29334896, year = {2018}, author = {Skinnider, MA and Johnston, CW and Merwin, NJ and Dejong, CA and Magarvey, NA}, title = {Global analysis of prokaryotic tRNA-derived cyclodipeptide biosynthesis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {45}, pmid = {29334896}, issn = {1471-2164}, mesh = {Algorithms ; Bacteria/*genetics ; Dipeptides/*biosynthesis ; Genomics ; Open Reading Frames ; Peptides, Cyclic/*biosynthesis ; RNA, Transfer/*metabolism ; }, abstract = {BACKGROUND: Among naturally occurring small molecules, tRNA-derived cyclodipeptides are a class that have attracted attention for their diverse and desirable biological activities. However, no tools are available to link cyclodipeptide synthases identified within prokaryotic genome sequences to their chemical products. Consequently, it is unclear how many genetically encoded cyclodipeptides represent novel products, and which producing organisms should be targeted for discovery.

RESULTS: We developed a pipeline for identification and classification of cyclodipeptide biosynthetic gene clusters and prediction of aminoacyl-tRNA substrates and complete chemical structures. We leveraged this tool to conduct a global analysis of tRNA-derived cyclodipeptide biosynthesis in 93,107 prokaryotic genomes, and compared predicted cyclodipeptides to known cyclodipeptide synthase products and all known chemically characterized cyclodipeptides. By integrating predicted chemical structures and gene cluster architectures, we created a unified map of known and unknown genetically encoded cyclodipeptides.

CONCLUSIONS: Our analysis suggests that sizeable regions of the chemical space encoded within sequenced prokaryotic genomes remain unexplored. Our map of the landscape of genetically encoded cyclodipeptides provides candidates for targeted discovery of novel compounds. The integration of our pipeline into a user-friendly web application provides a resource for further discovery of cyclodipeptides in newly sequenced prokaryotic genomes.}, } @article {pmid29334895, year = {2018}, author = {Koko, M and Abdallah, MOE and Amin, M and Ibrahim, M}, title = {Challenges imposed by minor reference alleles on the identification and reporting of clinical variants from exome data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {46}, pmid = {29334895}, issn = {1471-2164}, mesh = {*Alleles ; Gene Frequency ; *Genetic Variation ; Genome, Human ; Humans ; Reference Standards ; Venous Thrombosis/genetics ; *Whole Exome Sequencing/standards ; }, abstract = {BACKGROUND: The conventional variant calling of pathogenic alleles in exome and genome sequencing requires the presence of the non-pathogenic alleles as genome references. This hinders the correct identification of variants with minor and/or pathogenic reference alleles warranting additional approaches for variant calling.

RESULTS: More than 26,000 Exome Aggregation Consortium (ExAC) variants have a minor reference allele including variants with known ClinVar disease alleles. For instance, in a number of variants related to clotting disorders, the phenotype-associated allele is a human genome reference allele (rs6025, rs6003, rs1799983, and rs2227564 using the assembly hg19). We highlighted how the current variant calling standards miss homozygous reference disease variants in these sites and provided a bioinformatic panel that can be used to screen these variants using commonly available variant callers. We present exome sequencing results from an individual with venous thrombosis to emphasize how pathogenic alleles in clinically relevant variants escape variant calling while non-pathogenic alleles are detected.

CONCLUSIONS: This article highlights the importance of specialized variant calling strategies in clinical variants with minor reference alleles especially in the context of personal genomes and exomes. We provide here a simple strategy to screen potential disease-causing variants when present in homozygous reference state.}, } @article {pmid29334894, year = {2018}, author = {Li, Y and Xiang, Y and Xu, C and Shen, H and Deng, H}, title = {Rare variant association analysis in case-parents studies by allowing for missing parental genotypes.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {7}, pmid = {29334894}, issn = {1471-2156}, support = {R01 AR059781/AR/NIAMS NIH HHS/United States ; R01 AR069055/AR/NIAMS NIH HHS/United States ; D43 TW009107/TW/FIC NIH HHS/United States ; R01 GM109068/GM/NIGMS NIH HHS/United States ; R01 AR057049/AR/NIAMS NIH HHS/United States ; P20 GM109036/GM/NIGMS NIH HHS/United States ; R01 MH104680/MH/NIMH NIH HHS/United States ; R01 MH107354/MH/NIMH NIH HHS/United States ; }, mesh = {Computer Simulation ; Gene Frequency ; *Genetic Association Studies ; Genetic Predisposition to Disease ; *Genotype ; Humans ; Models, Genetic ; *Pedigree ; }, abstract = {BACKGROUND: The development of next-generation sequencing technologies has facilitated the identification of rare variants. Family-based design is commonly used to effectively control for population admixture and substructure, which is more prominent for rare variants. Case-parents studies, as typical strategies in family-based design, are widely used in rare variant-disease association analysis. Current methods in case-parents studies are based on complete case-parents data; however, parental genotypes may be missing in case-parents trios, and removing these data may lead to a loss in statistical power. The present study focuses on testing for rare variant-disease association in case-parents study by allowing for missing parental genotypes.

RESULTS: In this report, we extended the collapsing method for rare variant association analysis in case-parents studies to allow for missing parental genotypes, and investigated the performance of two methods by using the difference of genotypes between affected offspring and their corresponding "complements" in case-parent trios and TDT framework. Using simulations, we showed that, compared with the methods just only using complete case-parents data, the proposed strategy allowing for missing parental genotypes, or even adding unrelated affected individuals, can greatly improve the statistical power and meanwhile is not affected by population stratification.

CONCLUSIONS: We conclude that adding case-parents data with missing parental genotypes to complete case-parents data set can greatly improve the power of our strategy for rare variant-disease association.}, } @article {pmid29334893, year = {2018}, author = {Jiao, Y and Li, R and Wu, C and Ding, Y and Liu, Y and Jia, D and Wang, L and Xu, X and Zhu, J and Zheng, M and Jia, J}, title = {High-sensitivity HLA typing by Saturated Tiling Capture Sequencing (STC-Seq).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {50}, pmid = {29334893}, issn = {1471-2164}, support = {No.2016YFC0902702//National Program on Key Research Project of China/International ; 2017YFA0104901//National Program on Key Research Project of China/International ; LR15C060001//Nature Science Foundation of Zhejiang Province/International ; }, mesh = {HLA Antigens/genetics ; *High-Throughput Nucleotide Sequencing ; Histocompatibility Testing/*methods ; Humans ; *Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Highly polymorphic human leukocyte antigen (HLA) genes are responsible for fine-tuning the adaptive immune system. High-resolution HLA typing is important for the treatment of autoimmune and infectious diseases. Additionally, it is routinely performed for identifying matched donors in transplantation medicine. Although many HLA typing approaches have been developed, the complexity, low-efficiency and high-cost of current HLA-typing assays limit their application in population-based high-throughput HLA typing for donors, which is required for creating large-scale databases for transplantation and precision medicine.

RESULTS: Here, we present a cost-efficient Saturated Tiling Capture Sequencing (STC-Seq) approach to capturing 14 HLA class I and II genes. The highly efficient capture (an approximately 23,000-fold enrichment) of these genes allows for simplified allele calling. Tests on five genes (HLA-A/B/C/DRB1/DQB1) from 31 human samples and 351 datasets using STC-Seq showed results that were 98% consistent with the known two sets of digitals (field1 and field2) genotypes. Additionally, STC can capture genomic DNA fragments longer than 3 kb from HLA loci, making the library compatible with the third-generation sequencing.

CONCLUSIONS: STC-Seq is a highly accurate and cost-efficient method for HLA typing which can be used to facilitate the establishment of population-based HLA databases for the precision and transplantation medicine.}, } @article {pmid29334892, year = {2018}, author = {Chen, H and Zhang, W and Li, X and Pan, Y and Yan, S and Wang, Y}, title = {The genome of a prasinoviruses-related freshwater virus reveals unusual diversity of phycodnaviruses.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {49}, pmid = {29334892}, issn = {1471-2164}, support = {41376135//National Natural Science Foundation of China/International ; 31570112//National Natural Science Foundation of China/International ; }, mesh = {Biodiversity ; Fresh Water/virology ; Genes, Viral ; *Genome, Viral ; Histones/genetics ; Phycodnaviridae/classification/*genetics ; Phylogeny ; }, abstract = {BACKGROUND: Phycodnaviruses are widespread algae-infecting large dsDNA viruses and presently contain six genera: Chlorovirus, Prasinovirus, Prymnesiovirus, Phaeovirus, Coccolithovirus and Raphidovirus. The members in Prasinovirus are identified as marine viruses due to their marine algal hosts, while prasinovirus freshwater relatives remain rarely reported.

RESULTS: Here we present the complete genomic sequence of a novel phycodnavirus, Dishui Lake Phycodnavirus 1 (DSLPV1), which was assembled from Dishui Lake metagenomic datasets. DSLPV1 harbors a linear genome of 181,035 bp in length (G + C content: 52.7%), with 227 predicted genes and 2 tRNA encoding regions. Both comparative genomic and phylogenetic analyses indicate that the freshwater algal virus DSLPV1 is closely related to the members in Prasinovirus, a group of marine algae infecting viruses. In addition, a complete eukaryotic histone H3 variant was identified in the genome of DSLPV1, which is firstly detected in phycodnaviruses and contributes to understand the interaction between algal virus and its eukaryotic hosts.

CONCLUSION: It is in a freshwater ecosystem that a novel Prasinovirus-related viral complete genomic sequence is discovered, which sheds new light on the evolution and diversity of the algae infecting Phycodnaviridae.}, } @article {pmid29334891, year = {2018}, author = {Palkowski, M and Bielecki, W}, title = {Tuning iteration space slicing based tiled multi-core code implementing Nussinov's RNA folding.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {12}, pmid = {29334891}, issn = {1471-2105}, mesh = {*Algorithms ; Computational Biology/*methods ; Nucleic Acid Conformation ; RNA/chemistry ; *RNA Folding ; Time Factors ; }, abstract = {BACKGROUND: RNA folding is an ongoing compute-intensive task of bioinformatics. Parallelization and improving code locality for this kind of algorithms is one of the most relevant areas in computational biology. Fortunately, RNA secondary structure approaches, such as Nussinov's recurrence, involve mathematical operations over affine control loops whose iteration space can be represented by the polyhedral model. This allows us to apply powerful polyhedral compilation techniques based on the transitive closure of dependence graphs to generate parallel tiled code implementing Nussinov's RNA folding. Such techniques are within the iteration space slicing framework - the transitive dependences are applied to the statement instances of interest to produce valid tiles. The main problem at generating parallel tiled code is defining a proper tile size and tile dimension which impact parallelism degree and code locality.

RESULTS: To choose the best tile size and tile dimension, we first construct parallel parametric tiled code (parameters are variables defining tile size). With this purpose, we first generate two nonparametric tiled codes with different fixed tile sizes but with the same code structure and then derive a general affine model, which describes all integer factors available in expressions of those codes. Using this model and known integer factors present in the mentioned expressions (they define the left-hand side of the model), we find unknown integers in this model for each integer factor available in the same fixed tiled code position and replace in this code expressions, including integer factors, with those including parameters. Then we use this parallel parametric tiled code to implement the well-known tile size selection (TSS) technique, which allows us to discover in a given search space the best tile size and tile dimension maximizing target code performance.

CONCLUSIONS: For a given search space, the presented approach allows us to choose the best tile size and tile dimension in parallel tiled code implementing Nussinov's RNA folding. Experimental results, received on modern Intel multi-core processors, demonstrate that this code outperforms known closely related implementations when the length of RNA strands is bigger than 2500.}, } @article {pmid29334890, year = {2018}, author = {Magwanga, RO and Lu, P and Kirungu, JN and Lu, H and Wang, X and Cai, X and Zhou, Z and Zhang, Z and Salih, H and Wang, K and Liu, F}, title = {Characterization of the late embryogenesis abundant (LEA) proteins family and their role in drought stress tolerance in upland cotton.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {6}, pmid = {29334890}, issn = {1471-2156}, mesh = {Droughts ; Gene Duplication ; Gossypium/chemistry/classification/*genetics/*physiology ; Phylogeny ; Plant Proteins/*genetics/metabolism ; Seeds/chemistry/*genetics ; Synteny ; *Transcriptome ; }, abstract = {BACKGROUND: Late embryogenesis abundant (LEA) proteins are large groups of hydrophilic proteins with major role in drought and other abiotic stresses tolerance in plants. In-depth study and characterization of LEA protein families have been carried out in other plants, but not in upland cotton. The main aim of this research work was to characterize the late embryogenesis abundant (LEA) protein families and to carry out gene expression analysis to determine their potential role in drought stress tolerance in upland cotton. Increased cotton production in the face of declining precipitation and availability of fresh water for agriculture use is the focus for breeders, cotton being the backbone of textile industries and a cash crop for many countries globally.

RESULTS: In this work, a total of 242, 136 and 142 LEA genes were identified in G. hirsutum, G. arboreum and G. raimondii respectively. The identified genes were classified into eight groups based on their conserved domain and phylogenetic tree analysis. LEA 2 were the most abundant, this could be attributed to their hydrophobic character. Upland cotton LEA genes have fewer introns and are distributed in all chromosomes. Majority of the duplicated LEA genes were segmental. Syntenic analysis showed that greater percentages of LEA genes are conserved. Segmental gene duplication played a key role in the expansion of LEA genes. Sixty three miRNAs were found to target 89 genes, such as miR164, ghr-miR394 among others. Gene ontology analysis revealed that LEA genes are involved in desiccation and defense responses. Almost all the LEA genes in their promoters contained ABRE, MBS, W-Box and TAC-elements, functionally known to be involved in drought stress and other stress responses. Majority of the LEA genes were involved in secretory pathways. Expression profile analysis indicated that most of the LEA genes were highly expressed in drought tolerant cultivars Gossypium tomentosum as opposed to drought susceptible, G. hirsutum. The tolerant genotypes have a greater ability to modulate genes under drought stress than the more susceptible upland cotton cultivars.

CONCLUSION: The finding provides comprehensive information on LEA genes in upland cotton, G. hirsutum and possible function in plants under drought stress.}, } @article {pmid29334889, year = {2018}, author = {Qiao, Y and Xiong, Y and Gao, H and Zhu, X and Chen, P}, title = {Protein-protein interface hot spots prediction based on a hybrid feature selection strategy.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {14}, pmid = {29334889}, issn = {1471-2105}, support = {21403002//National Natural Science Foundation of China (CN)/International ; 31601074//National Natural Science Foundation of China/International ; 11626052//National Natural Science Foundation of China/International ; 61672035//National Natural Science Foundation of China/International ; 61300058//National Natural Science Foundation of China/International ; 201601296//Doctoral Fund of Liaoning Province/International ; }, mesh = {*Algorithms ; Computational Biology/*methods ; Databases, Protein ; Humans ; Proteins/*chemistry ; Support Vector Machine ; }, abstract = {BACKGROUND: Hot spots are interface residues that contribute most binding affinity to protein-protein interaction. A compact and relevant feature subset is important for building machine learning methods to predict hot spots on protein-protein interfaces. Although different methods have been used to detect the relevant feature subset from a variety of features related to interface residues, it is still a challenge to detect the optimal feature subset for building the final model.

RESULTS: In this study, three different feature selection methods were compared to propose a new hybrid feature selection strategy. This new strategy was proved to effectively reduce the feature space when we were building the prediction models for identifying hotspot residues. It was tested on eighty-two features, both conventional and newly proposed. According to the strategy, combining the feature subsets selected by decision tree and mRMR (maximum Relevance Minimum Redundancy) individually, we were able to build a model with 6 features by using a PSFS (Pseudo Sequential Forward Selection) process. Compared with other state-of-art methods for the independent test set, our model had shown better or comparable predictive performances (with F-measure 0.622 and recall 0.821). Analysis of the 6 features confirmed that our newly proposed feature CNSV_REL1 was important for our model. The analysis also showed that the complementarity between features should be considered as an important aspect when conducting the feature selection.

CONCLUSION: In this study, most important of all, a new strategy for feature selection was proposed and proved to be effective in selecting the optimal feature subset for building prediction models, which can be used to predict hot spot residues on protein-protein interfaces. Moreover, two aspects, the generalization of the single feature and the complementarity between features, were proved to be of great importance and should be considered in feature selection methods. Finally, our newly proposed feature CNSV_REL1 had been proved an alternative and effective feature in predicting hot spots by our study. Our model is available for users through a webserver: http://zhulab.ahu.edu.cn/iPPHOT/ .}, } @article {pmid29334888, year = {2018}, author = {Chiu, DS and Talhouk, A}, title = {diceR: an R package for class discovery using an ensemble driven approach.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {11}, pmid = {29334888}, issn = {1471-2105}, mesh = {*Algorithms ; Cluster Analysis ; Databases as Topic ; Humans ; *Software ; }, abstract = {BACKGROUND: Given a set of features, researchers are often interested in partitioning objects into homogeneous clusters. In health research, cancer research in particular, high-throughput data is collected with the aim of segmenting patients into sub-populations to aid in disease diagnosis, prognosis or response to therapy. Cluster analysis, a class of unsupervised learning techniques, is often used for class discovery. Cluster analysis suffers from some limitations, including the need to select up-front the algorithm to be used as well as the number of clusters to generate, in addition, there may exist several groupings consistent with the data, making it very difficult to validate a final solution. Ensemble clustering is a technique used to mitigate these limitations and facilitate the generalization and reproducibility of findings in new cohorts of patients.

RESULTS: We introduce diceR (diverse cluster ensemble in R), a software package available on CRAN: https://CRAN.R-project.org/package=diceR CONCLUSIONS: diceR is designed to provide a set of tools to guide researchers through a general cluster analysis process that relies on minimizing subjective decision-making. Although developed in a biological context, the tools in diceR are data-agnostic and thus can be applied in different contexts.}, } @article {pmid29334887, year = {2018}, author = {Legendre, A and Angel, E and Tahi, F}, title = {Bi-objective integer programming for RNA secondary structure prediction with pseudoknots.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {13}, pmid = {29334887}, issn = {1471-2105}, mesh = {Algorithms ; Computational Biology/*methods ; Databases, Genetic ; Models, Molecular ; *Nucleic Acid Conformation ; RNA/*chemistry ; Time Factors ; }, abstract = {BACKGROUND: RNA structure prediction is an important field in bioinformatics, and numerous methods and tools have been proposed. Pseudoknots are specific motifs of RNA secondary structures that are difficult to predict. Almost all existing methods are based on a single model and return one solution, often missing the real structure. An alternative approach would be to combine different models and return a (small) set of solutions, maximizing its quality and diversity in order to increase the probability that it contains the real structure.

RESULTS: We propose here an original method for predicting RNA secondary structures with pseudoknots, based on integer programming. We developed a generic bi-objective integer programming algorithm allowing to return optimal and sub-optimal solutions optimizing simultaneously two models. This algorithm was then applied to the combination of two known models of RNA secondary structure prediction, namely MEA and MFE. The resulting tool, called BiokoP, is compared with the other methods in the literature. The results show that the best solution (structure with the highest F1-score) is, in most cases, given by BiokoP. Moreover, the results of BiokoP are homogeneous, regardless of the pseudoknot type or the presence or not of pseudoknots. Indeed, the F1-scores are always higher than 70% for any number of solutions returned.

CONCLUSION: The results obtained by BiokoP show that combining the MEA and the MFE models, as well as returning several optimal and several sub-optimal solutions, allow to improve the prediction of secondary structures. One perspective of our work is to combine better mono-criterion models, in particular to combine a model based on the comparative approach with the MEA and the MFE models. This leads to develop in the future a new multi-objective algorithm to combine more than two models. BiokoP is available on the EvryRNA platform: https://EvryRNA.ibisc.univ-evry.fr .}, } @article {pmid29334685, year = {2018}, author = {Serra-Garcia, M and Peri, V and Süsstrunk, R and Bilal, OR and Larsen, T and Villanueva, LG and Huber, SD}, title = {Observation of a phononic quadrupole topological insulator.}, journal = {Nature}, volume = {555}, number = {7696}, pages = {342-345}, pmid = {29334685}, issn = {1476-4687}, abstract = {The modern theory of charge polarization in solids is based on a generalization of Berry's phase. The possibility of the quantization of this phase arising from parallel transport in momentum space is essential to our understanding of systems with topological band structures. Although based on the concept of charge polarization, this same theory can also be used to characterize the Bloch bands of neutral bosonic systems such as photonic or phononic crystals. The theory of this quantized polarization has recently been extended from the dipole moment to higher multipole moments. In particular, a two-dimensional quantized quadrupole insulator is predicted to have gapped yet topological one-dimensional edge modes, which stabilize zero-dimensional in-gap corner states. However, such a state of matter has not previously been observed experimentally. Here we report measurements of a phononic quadrupole topological insulator. We experimentally characterize the bulk, edge and corner physics of a mechanical metamaterial (a material with tailored mechanical properties) and find the predicted gapped edge and in-gap corner states. We corroborate our findings by comparing the mechanical properties of a topologically non-trivial system to samples in other phases that are predicted by the quadrupole theory. These topological corner states are an important stepping stone to the experimental realization of topologically protected wave guides in higher dimensions, and thereby open up a new path for the design of metamaterials.}, } @article {pmid29334655, year = {2018}, author = {Ewald, JC}, title = {How yeast coordinates metabolism, growth and division.}, journal = {Current opinion in microbiology}, volume = {45}, number = {}, pages = {1-7}, doi = {10.1016/j.mib.2017.12.012}, pmid = {29334655}, issn = {1879-0364}, abstract = {All cells, especially single cell organisms, need to adapt their metabolism, growth and division coordinately to the available nutrients. This coordination is mediated by extensive cross-talk between nutrient signaling, metabolism, growth, and the cell division cycle, which is only gradually being uncovered: Nutrient signaling not only controls entry into the cell cycle at the G1/S transition, but all phases of the cell cycle. Metabolites are even sensed directly by cell cycle regulators to prevent cell cycle progression in absence of sufficient metabolic fluxes. In turn, cell cycle regulators such as the cyclin-dependent kinase directly control metabolic fluxes during cell cycle progression. In this review, I highlight some recent advances in our understanding of how metabolism and the cell division cycle are coordinated in the model organism Saccharomyces cerevisiae.}, } @article {pmid29333060, year = {2018}, author = {Dunbar, RIM and Sosis, R}, title = {Optimising human community sizes.}, journal = {Evolution and human behavior : official journal of the Human Behavior and Evolution Society}, volume = {39}, number = {1}, pages = {106-111}, pmid = {29333060}, issn = {1090-5138}, support = {295663//European Research Council/International ; }, abstract = {We examine community longevity as a function of group size in three historical, small scale agricultural samples. Community sizes of 50, 150 and 500 are disproportionately more common than other sizes; they also have greater longevity. These values mirror the natural layerings in hunter-gatherer societies and contemporary personal networks. In addition, a religious ideology seems to play an important role in allowing larger communities to maintain greater cohesion for longer than a strictly secular ideology does. The differences in optimal community size may reflect the demands of different ecologies, economies and social contexts, but, as yet, we have no explanation as to why these numbers seem to function socially so much more effectively than other values.}, } @article {pmid29332945, year = {2018}, author = {Byrd, AL and Belkaid, Y and Segre, JA}, title = {The human skin microbiome.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {143-155}, pmid = {29332945}, issn = {1740-1534}, abstract = {Functioning as the exterior interface of the human body with the environment, skin acts as a physical barrier to prevent the invasion of foreign pathogens while providing a home to the commensal microbiota. The harsh physical landscape of skin, particularly the desiccated, nutrient-poor, acidic environment, also contributes to the adversity that pathogens face when colonizing human skin. Despite this, the skin is colonized by a diverse microbiota. In this Review, we describe amplicon and shotgun metagenomic DNA sequencing studies that have been used to assess the taxonomic diversity of microorganisms that are associated with skin from the kingdom to the strain level. We discuss recent insights into skin microbial communities, including their composition in health and disease, the dynamics between species and interactions with the immune system, with a focus on Propionibacterium acnes, Staphylococcus epidermidis and Staphylococcus aureus.}, } @article {pmid29332944, year = {2018}, author = {Hofer, U}, title = {Fungal pathogenesis: Wheat stem rust effectors revealed.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {65}, pmid = {29332944}, issn = {1740-1534}, } @article {pmid29332943, year = {2018}, author = {Hofer, U}, title = {Bacterial physiology: It's a wrap for Burkholderia flagella.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {65}, pmid = {29332943}, issn = {1740-1534}, } @article {pmid29332942, year = {2018}, author = {Medina, RA}, title = {1918 influenza virus: 100 years on, are we prepared against the next influenza pandemic?.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {61-62}, pmid = {29332942}, issn = {1740-1534}, } @article {pmid29332941, year = {2018}, author = {Du Toit, A}, title = {Bacterial pathogenesis: Clostridium difficile is sweet on trehalose.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {64}, pmid = {29332941}, issn = {1740-1534}, } @article {pmid29332940, year = {2018}, author = {Du Toit, A}, title = {Cellular microbiology: Many pathogens, one host receptor.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {64}, pmid = {29332940}, issn = {1740-1534}, } @article {pmid29332939, year = {2018}, author = {Hofer, U}, title = {Metagenomics: Setting the bar for mycobiome analysis.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {65}, pmid = {29332939}, issn = {1740-1534}, } @article {pmid29332159, year = {2018}, author = {Klein, SJ and O'Neill, RJ}, title = {Transposable elements: genome innovation, chromosome diversity, and centromere conflict.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {1-2}, pages = {5-23}, pmid = {29332159}, issn = {1573-6849}, support = {1613806//Directorate for Biological Sciences/International ; }, mesh = {Centromere/genetics ; DNA Transposable Elements/*genetics ; DNA, Satellite ; Genome/*genetics ; Humans ; Retroelements/genetics ; }, abstract = {Although it was nearly 70 years ago when transposable elements (TEs) were first discovered "jumping" from one genomic location to another, TEs are now recognized as contributors to genomic innovations as well as genome instability across a wide variety of species. In this review, we illustrate the ways in which active TEs, specifically retroelements, can create novel chromosome rearrangements and impact gene expression, leading to disease in some cases and species-specific diversity in others. We explore the ways in which eukaryotic genomes have evolved defense mechanisms to temper TE activity and the ways in which TEs continue to influence genome structure despite being rendered transpositionally inactive. Finally, we focus on the role of TEs in the establishment, maintenance, and stabilization of critical, yet rapidly evolving, chromosome features: eukaryotic centromeres. Across centromeres, specific types of TEs participate in genomic conflict, a balancing act wherein they are actively inserting into centromeric domains yet are harnessed for the recruitment of centromeric histones and potentially new centromere formation.}, } @article {pmid29332140, year = {2018}, author = {Sharma, A and Ponmariappan, S and Sarita, R and Alam, SI and Kamboj, DV and Shukla, S}, title = {Identification of Cross Reactive Antigens of C. botulinum Types A, B, E & F by Immunoproteomic Approach.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {531-540}, pmid = {29332140}, issn = {1432-0991}, support = {F .2-1/2010 (SA-1)//University Grants Commission/ ; }, mesh = {Animals ; Bacterial Proteins/chemistry/immunology ; Botulinum Toxins/*chemistry/immunology ; Botulism/immunology/*microbiology ; Clostridium botulinum/*chemistry/genetics/immunology ; Electrophoresis, Gel, Two-Dimensional ; Enzyme-Linked Immunosorbent Assay ; Humans ; Mice ; Mice, Inbred BALB C ; }, abstract = {Diseases triggered by microorganisms can be controlled by vaccines, which need neutralizing antigens. Hence, it is very crucial to identify extremely efficient immunogens for immune prevention. Botulism, a fatal neuroparalytic disease, is caused by botulinum neurotoxins produced by the anaerobic, Gram-positive spore-forming bacteria, Clostridium botulinum. Food-borne botulism and iatrogenic botulism are caused by botulinum toxin. Wound botulism, infant botulism, and adult intestinal botulism are caused by primarily C. botulinum followed by secondary intoxication. To identify protective antigens, whole cell proteome of C. botulinum type B was separated by two-dimensional gel electrophoresis. 2-D gel of whole cell proteins was probed with hyper immune sera of whole cell proteins of C. botulinum types A, E, and F. Six cross immunoreactive proteins were identified. These immunoreactive proteins will be further tested for developing vaccines and serodiagnostic markers against botulism.}, } @article {pmid29332139, year = {2018}, author = {Quinn, B and Traglia, GM and Nguyen, M and Martinez, J and Liu, C and Fernandez, JS and Ramirez, MS}, title = {Effect of Host Human Products on Natural Transformation in Acinetobacter baumannii.}, journal = {Current microbiology}, volume = {}, number = {}, pages = {}, doi = {10.1007/s00284-017-1417-5}, pmid = {29332139}, issn = {1432-0991}, support = {MHIRT 2T37MD001368//National Institute on Minority Health and Health Disparities, National Institute of Health/ ; }, abstract = {Our previous data show that serum albumin can trigger natural transformation in Acinetobacter baumannii. However, extracellular matrix/basal membrane components, norepinephrine, and mucin did not have a significant effect on this process. Therefore, the effect of human products appears to be albumin specific, as both BSA and HSA have been shown to increase of natural transformation.}, } @article {pmid29331767, year = {2018}, author = {Woznica, A and King, N}, title = {Lessons from simple marine models on the bacterial regulation of eukaryotic development.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {108-116}, pmid = {29331767}, issn = {1879-0364}, support = {/HHMI/Howard Hughes Medical Institute/United States ; R01 GM099533/GM/NIGMS NIH HHS/United States ; }, mesh = {Aquatic Organisms/genetics/growth & development/physiology ; Bacteria/*genetics ; Environment ; Eukaryota/*genetics/growth & development/physiology ; *Gene Expression Regulation ; Lipids/physiology ; Macromolecular Substances/metabolism ; }, abstract = {Molecular cues from environmental bacteria influence important developmental decisions in diverse marine eukaryotes. Yet, relatively little is understood about the mechanisms underlying these interactions, in part because marine ecosystems are dynamic and complex. With the help of simple model systems, including the choanoflagellate Salpingoeca rosetta, we have begun to uncover the bacterial cues that shape eukaryotic development in the ocean. Here, we review how diverse bacterial cues-from lipids to macromolecules-regulate development in marine eukaryotes. It is becoming clear that there are networks of chemical information circulating in the ocean, with both eukaryotes and bacteria acting as nodes; one eukaryote can precisely respond to cues from several diverse environmental bacteria, and a single environmental bacterium can regulate the development of different eukaryotes.}, } @article {pmid29331683, year = {2018}, author = {Springer, MS and Murphy, WJ and Roca, AL}, title = {Appropriate fossil calibrations and tree constraints uphold the Mesozoic divergence of solenodons from other extant mammals.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {158-165}, doi = {10.1016/j.ympev.2018.01.007}, pmid = {29331683}, issn = {1095-9513}, mesh = {Animals ; Calibration ; Cuba ; Evolution, Molecular ; *Fossils ; Mammals/*classification ; *Phylogeny ; Time Factors ; }, abstract = {The mammalian order Eulipotyphla includes four extant families of insectivorans: Solenodontidae (solenodons); Talpidae (moles); Soricidae (shrews); and Erinaceidae (hedgehogs). Of these, Solenodontidae includes only two extant species, which are endemic to the largest islands of the Greater Antilles: Cuba and Hispaniola. Most molecular studies suggest that eulipotyphlan families diverged from each other across several million years, with the basal split between Solenodontidae and other families occurring in the Late Cretaceous. By contrast, Sato et al. (2016) suggest that eulipotyphlan families diverged from each other in a polytomy ∼58.6 million years ago (Mya). This more recent divergence estimate for Solenodontidae versus other extant eulipotyphlans suggests that solenodons must have arrived in the Greater Antilles via overwater dispersal rather than vicariance. Here, we show that the young timetree estimates for eulipotyphlan families and the polytomy are due to an inverted ingroup-outgroup arrangement of the tree, the result of using Tracer rather than TreeAnnotator to compile interfamilial divergence times, and of not enforcing the monophly of well-established clades such as Laurasiatheria and Eulipotyphla. Finally, Sato et al.'s (2016) timetree includes several zombie lineages where estimated divergence times are much younger than minimum ages that are implied by the fossil record. We reanalyzed Sato et al.'s (2016) original data with enforced monophyly for well-established clades and updated fossil calibrations that eliminate the inference of zombie lineages. Our resulting timetrees, which were compiled with TreeAnnotator rather than Tracer, produce dates that are in good agreement with other recent studies and place the basal split between Solenodontidae and other eulipotyphlans in the Late Cretaceous.}, } @article {pmid29331499, year = {2018}, author = {Mercer, EJ and Lin, YF and Cohen-Gould, L and Evans, T}, title = {Hspb7 is a cardioprotective chaperone facilitating sarcomeric proteostasis.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {41-55}, pmid = {29331499}, issn = {1095-564X}, support = {R01 HL111400/HL/NHLBI NIH HHS/United States ; R35 HL135778/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Autophagy/genetics ; Cardiomyopathies/*embryology/genetics/pathology ; Filamins/genetics/metabolism ; HSP27 Heat-Shock Proteins/genetics/*metabolism ; Humans ; Myocytes, Cardiac/metabolism/pathology ; *Proteostasis ; Sarcomeres/genetics/*metabolism ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Small heat shock proteins are chaperones with variable mechanisms of action. The function of cardiac family member Hspb7 is unknown, despite being identified through GWAS as a potential cardiomyopathy risk gene. We discovered that zebrafish hspb7 mutants display mild focal cardiac fibrosis and sarcomeric abnormalities. Significant mortality was observed in adult hspb7 mutants subjected to exercise stress, demonstrating a genetic and environmental interaction that determines disease outcome. We identified large sarcomeric proteins FilaminC and Titin as Hspb7 binding partners in cardiac cells. Damaged FilaminC undergoes autophagic processing to maintain sarcomeric homeostasis. Loss of Hspb7 in zebrafish or human cardiomyocytes stimulated autophagic pathways and expression of the sister gene encoding Hspb5. Inhibiting autophagy caused FilaminC aggregation in HSPB7 mutant human cardiomyocytes and developmental cardiomyopathy in hspb7 mutant zebrafish embryos. These studies highlight the importance of damage-processing networks in cardiomyocytes, and a previously unrecognized role in this context for Hspb7.}, } @article {pmid29331498, year = {2018}, author = {Slota, LA and McClay, DR}, title = {Identification of neural transcription factors required for the differentiation of three neuronal subtypes in the sea urchin embryo.}, journal = {Developmental biology}, volume = {435}, number = {2}, pages = {138-149}, pmid = {29331498}, issn = {1095-564X}, support = {P01 HD037105/HD/NICHD NIH HHS/United States ; P01 HD039948/HD/NICHD NIH HHS/United States ; R01 HD014483/HD/NICHD NIH HHS/United States ; }, mesh = {Achaete-Scute Complex Genome Region/physiology ; Animals ; Ectoderm/*cytology ; *Gene Expression Regulation, Developmental ; Gene Regulatory Networks/*genetics ; Intracellular Signaling Peptides and Proteins/physiology ; Lytechinus/cytology/*embryology ; Membrane Proteins/physiology ; Morpholinos/pharmacology ; Nerve Tissue Proteins/*physiology ; Neurogenesis/*physiology ; Neurons/classification/*cytology ; RNA, Antisense/pharmacology ; Receptors, Notch/physiology ; Transcription Factors/*physiology ; }, abstract = {Correct patterning of the nervous system is essential for an organism's survival and complex behavior. Embryologists have used the sea urchin as a model for decades, but our understanding of sea urchin nervous system patterning is incomplete. Previous histochemical studies identified multiple neurotransmitters in the pluteus larvae of several sea urchin species. However, little is known about how, where and when neural subtypes are differentially specified during development. Here, we examine the molecular mechanisms of neuronal subtype specification in 3 distinct neural subtypes in the Lytechinus variegatus larva. We show that these subtypes are specified through Delta/Notch signaling and identify a different transcription factor required for the development of each neural subtype. Our results show achaete-scute and neurogenin are proneural for the serotonergic neurons of the apical organ and cholinergic neurons of the ciliary band, respectively. We also show that orthopedia is not proneural but is necessary for the differentiation of the cholinergic/catecholaminergic postoral neurons. Interestingly, these transcription factors are used similarly during vertebrate neurogenesis. We believe this study is a starting point for building a neural gene regulatory network in the sea urchin and for finding conserved deuterostome neurogenic mechanisms.}, } @article {pmid29331490, year = {2018}, author = {Schrider, DR and Kern, AD}, title = {Supervised Machine Learning for Population Genetics: A New Paradigm.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {301-312}, pmid = {29331490}, issn = {0168-9525}, support = {K99 HG008696/HG/NHGRI NIH HHS/United States ; R01 GM117241/GM/NIGMS NIH HHS/United States ; }, mesh = {Biological Evolution ; Data Mining/*methods ; Datasets as Topic ; *Genetics, Population ; *Genome, Human ; Humans ; Selection, Genetic ; *Supervised Machine Learning ; }, abstract = {As population genomic datasets grow in size, researchers are faced with the daunting task of making sense of a flood of information. To keep pace with this explosion of data, computational methodologies for population genetic inference are rapidly being developed to best utilize genomic sequence data. In this review we discuss a new paradigm that has emerged in computational population genomics: that of supervised machine learning (ML). We review the fundamentals of ML, discuss recent applications of supervised ML to population genetics that outperform competing methods, and describe promising future directions in this area. Ultimately, we argue that supervised ML is an important and underutilized tool that has considerable potential for the world of evolutionary genomics.}, } @article {pmid29331268, year = {2018}, author = {Whittaker, C and Walker, M and Pion, SDS and Chesnais, CB and Boussinesq, M and Basáñez, MG}, title = {The Population Biology and Transmission Dynamics of Loa loa.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {335-350}, doi = {10.1016/j.pt.2017.12.003}, pmid = {29331268}, issn = {1471-5007}, mesh = {Animals ; Anthelmintics/therapeutic use ; Humans ; Loa/*physiology ; Loiasis/drug therapy/*parasitology/prevention & control/*transmission ; *Models, Biological ; }, abstract = {Endemic to Central Africa, loiasis - or African eye worm (caused by the filarial nematode Loa loa) - affects more than 10 million people. Despite causing ocular and systemic symptoms, it has typically been considered a benign condition, only of public health relevance because it impedes mass drug administration-based interventions against onchocerciasis and lymphatic filariasis in co-endemic areas. Recent research has challenged this conception, demonstrating excess mortality associated with high levels of infection, implying that loiasis warrants attention as an intrinsic public health problem. This review summarises available information on the key parasitological, entomological, and epidemiological characteristics of the infection and argues for the mobilisation of resources to control the disease, and the development of a mathematical transmission model to guide deployment of interventions.}, } @article {pmid29331230, year = {2018}, author = {Ruff, CB and Burgess, ML and Squyres, N and Junno, JA and Trinkaus, E}, title = {Lower limb articular scaling and body mass estimation in Pliocene and Pleistocene hominins.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {85-111}, doi = {10.1016/j.jhevol.2017.10.014}, pmid = {29331230}, issn = {1095-8606}, abstract = {Previous attempts to estimate body mass in pre-Holocene hominins have relied on prediction equations derived from relatively limited extant samples. Here we derive new equations to predict body mass from femoral head breadth and proximal tibial plateau breadth based on a large and diverse sample of modern humans (avoiding the problems associated with using diaphyseal dimensions and/or cadaveric reference samples). In addition, an adjustment for the relatively small femoral heads of non-Homo taxa is developed based on observed differences in hip to knee joint scaling. Body mass is then estimated for 214 terminal Miocene through Pleistocene hominin specimens. Mean body masses for non-Homo taxa range between 39 and 49 kg (39-45 kg if sex-specific means are averaged), with no consistent temporal trend (6-1.85 Ma). Mean body mass increases in early Homo (2.04-1.77 Ma) to 55-59 kg, and then again dramatically in Homo erectus and later archaic middle Pleistocene Homo, to about 70 kg. The same average body mass is maintained in late Pleistocene archaic Homo and early anatomically modern humans through the early/middle Upper Paleolithic (0.024 Ma), only declining in the late Upper Paleolithic, with regional variation. Sexual dimorphism in body mass is greatest in Australopithecus afarensis (log[male/female] = 1.54), declines in Australopithecus africanus and Paranthropus robustus (log ratio 1.36), and then again in early Homo and middle and late Pleistocene archaic Homo (log ratio 1.20-1.27), although it remains somewhat elevated above that of living and middle/late Pleistocene anatomically modern humans (log ratio about 1.15).}, } @article {pmid29331229, year = {2018}, author = {McHenry, LJ and de la Torre, I}, title = {Hominin raw material procurement in the Oldowan-Acheulean transition at Olduvai Gorge.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {378-401}, doi = {10.1016/j.jhevol.2017.11.010}, pmid = {29331229}, issn = {1095-8606}, abstract = {The lithic assemblages at the Oldowan-Acheulean transition in Bed II of Olduvai Gorge, Tanzania, represent a wide variety of raw materials reflecting both the diversity of volcanic, metamorphic, and sedimentary source materials available in the Olduvai basin and surroundings and the preferences of the tool-makers. A geochemical and petrographic systematic analysis of lava-derived archaeological stone tools, combined with textural and mineralogical characterization of quartzite, chert, and other metamorphic and sedimentary raw materials from two Middle and Upper Bed II sites, has enabled us to produce a comprehensive dataset and characterization of the rocks employed by Olduvai hominins, which is used here to establish a referential framework for future studies on Early Stone Age raw material provenancing. The use of rounded blanks for most lava-derived artifacts demonstrates that hominins were accessing lava in local stream channels. Most quartzite artifacts appear to derive from angular blocks, likely acquired at the source (predominantly Naibor Soit hill), though some do appear to be manufactured from stream-transported quartzite blanks. Raw material composition of the EF-HR assemblage indicates that Acheulean hominins selected high-quality lavas for the production of Large Cutting Tools. On the other hand, the HWK EE lithic assemblage suggests that raw material selectivity was not entirely based on rock texture, and other factors, such as blank shape and availability of natural angles suitable for flaking, played a major role in Oldowan reduction sequences.}, } @article {pmid29331038, year = {2018}, author = {Turnell, BR and Shaw, KL and Reeve, HK}, title = {Modeling strategic sperm allocation: Tailoring the predictions to the species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {414-425}, doi = {10.1111/evo.13423}, pmid = {29331038}, issn = {1558-5646}, abstract = {Two major challenges exist when empirically testing the predictions of sperm allocation theory. First, the study species must adhere to the assumptions of the model being tested. Unfortunately, the common assumption of sperm allocation models that females mate a maximum of once or twice does not hold for many, if not most, multiply and sequentially mating animals. Second, a model's parameters, which dictate its predictions, must be measured in the study species. Common examples of such parameters, female mating frequency and sperm precedence patterns, are unknown for many species used in empirical tests. Here, we present a broadly applicable model, appropriate for multiply, sequentially mating animals, and test it in three species for which data on all the relevant parameter values are available. The model predicts that relative allocation to virgin females, compared to nonvirgins, depends on the interaction between female mating rate and the sperm precedence pattern: relative allocation to virgins increases with female mating rate under first-male precedence, while the opposite is true under later-male precedence. Our model is moderately successful in predicting actual allocation patterns in the three species, including a cricket in which we measured the parameter values and performed an empirical test of allocation.}, } @article {pmid29331019, year = {2018}, author = {Fyon, F and Lenormand, T}, title = {Cis-regulator runaway and divergence in asexuals.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {426-439}, doi = {10.1111/evo.13424}, pmid = {29331019}, issn = {1558-5646}, abstract = {With the advent of new sequencing technologies, the evolution of gene expression is becoming a subject of intensive genomic research, with sparking debates upon the role played by these kinds of changes in adaptive evolution and speciation. In this article, we model expression evolution in species differing by their reproductive systems. We consider different rates of sexual versus asexual reproduction and the different type of parthenogenesis (apomixis and the various modes of automixis). We show that competition for expression leads to two selective processes on cis-regulatory regions that act independently to organism-level adaptation. Coevolution within regulatory networks allows these processes to occur without strongly modifying expression levels. First, cis-regulatory regions such as enhancers evolve in a runaway fashion because they automatically become associated to chromosomes purged from deleterious mutations ("Enhancer Runaway process"). Second, in clonal or nearly clonal species, homologous cis-regulatory regions tend to diverge, which leads to haploidization of expression, when they are sufficiently isolated from one another ("Enhancer Divergence process"). We show how these two processes cooccur and vary depending on the level of outcrossing, gene conversion, mitotic recombination, or recombination in automictic species. This study offers thus a baseline to understand patterns of expression evolution across the diversity of eukaryotic species.}, } @article {pmid29330556, year = {2018}, author = {Hirashima, T and Toyoshima, M and Moriyama, T and Sato, N}, title = {Evolution of the Phosphatidylcholine Biosynthesis Pathways in Green Algae: Combinatorial Diversity of Methyltransferases.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {68-76}, pmid = {29330556}, issn = {1432-1432}, abstract = {Phosphatidylcholine (PC) is one of the most common phospholipids in eukaryotes, although some green algae such as Chlamydomonas reinhardtii are known to lack PC. Recently, we detected PC in four species in the genus Chlamydomonas: C. applanata NIES-2202, C. asymmetrica NIES-2207, C. debaryana NIES-2212, and C. sphaeroides NIES-2242. To reveal the PC biosynthesis pathways in green algae and the evolutionary scenario involved in their diversity, we analyzed the PC biosynthesis genes in these four algae using draft genome sequences. Homology searches suggested that PC in these species is synthesized by phosphoethanolamine-N-methyltransferase (PEAMT) and/or phosphatidylethanolamine-N-methyltransferase (PEMT), both of which are absent in C. reinhardtii. Recombinant PEAMTs from these algae showed methyltransferase activity for phosphoethanolamine but not for monomethyl phosphoethanolamine in vitro, in contrast to land plant PEAMT, which catalyzes the three methylations from phosphoethanolamine to phosphocholine. This suggested an involvement of other methyltransferases in PC biosynthesis. Here, we characterized the putative phospholipid-N-methyltransferase (PLMT) genes of these species by genetic and phylogenetic analysis. Complementation assays using a PC biosynthesis-deficient yeast suggested that the PLMTs of these algae can synthesize PC from phosphatidylethanolamine. These results indicated that the PC biosynthesis pathways in green algae differ from those of land plants, although the enzymes involved are homologous. Phylogenetic analysis suggested that the PEAMTs and PLMTs in these algae were inherited from the common ancestor of green algae. The absence of PC biosynthesis in many Chlamydomonas species is likely a result of parallel losses of PEAMT and PLMT in this genus.}, } @article {pmid29330331, year = {2018}, author = {Armbruster, PA}, title = {Molecular pathways to nonbiting mosquitoes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {836-838}, pmid = {29330331}, issn = {1091-6490}, mesh = {Animals ; *Culicidae ; }, } @article {pmid29330330, year = {2018}, author = {Vandvik, V and Halbritter, AH and Telford, RJ}, title = {Greening up the mountain.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {833-835}, pmid = {29330330}, issn = {1091-6490}, mesh = {Chlorophyll ; *Ecosystem ; Hordeum ; Light ; Plant Leaves ; *Temperature ; }, } @article {pmid29330329, year = {2018}, author = {Paliou, C and Andrey, G}, title = {Large genomic insertion at the Shh locus results in hammer toes through enhancer adoption.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {839-841}, pmid = {29330329}, issn = {1091-6490}, mesh = {*Enhancer Elements, Genetic ; Genomics ; *Hammer Toe Syndrome ; Hedgehog Proteins/genetics ; Humans ; Toes ; }, } @article {pmid29330139, year = {2018}, author = {Kocot, KM and Tassia, MG and Halanych, KM and Swalla, BJ}, title = {Phylogenomics offers resolution of major tunicate relationships.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {166-173}, doi = {10.1016/j.ympev.2018.01.005}, pmid = {29330139}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Genomics ; Likelihood Functions ; *Phylogeny ; Urochordata/*classification/*genetics ; }, abstract = {Tunicata, a diverse clade of approximately 3000 described species of marine, filter-feeding chordates, is of great interest to researchers because tunicates are the closest living relatives of vertebrates and they facilitate comparative studies of our own biology. The group also includes numerous invasive species that cause considerable economic damage and some species of tunicates are edible. Despite their diversity and importance, relationships among major lineages of Tunicata are not completely resolved. Here, we supplemented public data with transcriptomes from seven species spanning the diversity of Tunicata and conducted phylogenomic analyses on data sets of up to 798 genes. Sensitivity analyses were employed to examine the influences of reducing compositional heterogeneity and branch-length heterogeneity. All analyses maximally supported a monophyletic Tunicata within Olfactores (Vertebrata + Tunicata). Within Tunicata, all analyses recovered Appendicularia sister to the rest of Tunicata and confirmed (with maximal support) that Thaliacea is nested within Ascidiacea. Stolidobranchia is the sister taxon to all other tunicates except Appendicularia. In most analyses, phlebobranch tunicates were recovered paraphyletic with respect to Aplousobranchia. Support for this topology varied but was strong in some cases. However, when only the 50 best genes based on compositional heterogeneity were analysed, we recovered Phlebobranchia and Aplousobranchia reciprocally monophyletic with strong support, consistent with most traditional morphology-based hypotheses. Examination of internode certainty also cast doubt on results of phlebobranch paraphyly, which may be due to limited taxon sampling. Taken together, these results provide a higher-level phylogenetic framework for our closest living invertebrate relatives.}, } @article {pmid29330138, year = {2018}, author = {Kieren, S and Sparreboom, M and Hochkirch, A and Veith, M}, title = {A biogeographic and ecological perspective to the evolution of reproductive behaviour in the family Salamandridae.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {98-109}, doi = {10.1016/j.ympev.2018.01.006}, pmid = {29330138}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; *Ecosystem ; Phylogeny ; *Phylogeography ; Salamandridae/classification/*physiology ; *Sexual Behavior, Animal ; Species Specificity ; Time Factors ; }, abstract = {Amphibians have a complex reproductive behaviour, which shows the highest diversity among tetrapodes. The family Salamandridae, distributed across the entire Holarctic, is one of the most diverse groups of extant salamanders comprising 114 species in 21 genera. The family has a remarkable diversity of courtship modes, amplexus and sperm transfer. It is often hypothesised that this diversity has evolved in adaptation to a specific mating and/or breeding habitat. We test this hypothesis based upon a phylogenetic reconstruction using the complete mitochondrial genome sequences of 45 Salamandridae species, representing all existing genera. We used ancestral character state reconstruction methods and geographic range models and applied relaxed Bayesian molecular clock models to discuss the results in a temporal framework of Salamandridae evolution. Our results show that the family Salamandridae started to diversify in the Late Cretaceous (ca. 87 mya) and is of Western Palearctic origin. Ancestral character state reconstruction predicts that its common ancestor was oviparous, mated on land without amplexus and probably showed a pin wheel spermatophore transfer, which is still found in the Italian endemic Salamandrina terdigidata. Our results suggest that several colonization of continents with subsequent radiations took place, once to the Nearctic and twice into Eastern Asian realms. However, these events were only in one case associated with a change in mating behaviour (dorsal amplexus in Nearctic newts). Around the Cretaceous-Paleogene boundary (K-Pg boundary) several Salamandridae lineages further diverged, again with no obvious changes in mating behaviour. Overall, there is no significant signal for mating character evolution being caused by changes in habitat type, with only a slight tendency that changes in mating habitat might have led to changes in the type of sperm transfer which in turn was associated with changes in the presence or absence of amplexus.}, } @article {pmid29329912, year = {2018}, author = {Angelo, JR and Tremblay, KD}, title = {Identification and fate mapping of the pancreatic mesenchyme.}, journal = {Developmental biology}, volume = {435}, number = {1}, pages = {15-25}, pmid = {29329912}, issn = {1095-564X}, support = {R01 DK087753/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Embryo, Mammalian/cytology/*embryology ; Mesoderm/cytology/*embryology ; Mice ; Organogenesis/*physiology ; Pancreas/cytology/*embryology ; }, abstract = {The murine pancreas buds from the ventral embryonic endoderm at approximately 8.75 dpc and a second pancreas bud emerges from the dorsal endoderm by 9.0 dpc. Although it is clear that secreted signals from adjacent mesoderm-derived sources are required for both the appropriate emergence and further refinement of the pancreatic endoderm, neither the exact signals nor the requisite tissue sources have been defined in mammalian systems. Herein we use DiI fate mapping of cultured murine embryos to identify the embryonic sources of both the early inductive and later condensed pancreatic mesenchyme. Despite being capable of supporting pancreas induction from dorsal endoderm in co-culture experiments, we find that in the context of the developing embryo, the dorsal aortae as well as the paraxial, intermediate, and lateral mesoderm derivatives only transiently associate with the dorsal pancreas bud, producing descendants that are decidedly anterior to the pancreas bud. Unlike these other mesoderm derivatives, the axial (notochord) descendants maintain association with the dorsal pre-pancreatic endoderm and early pancreas bud. This fate mapping data points to the notochord as the likely inductive source in vivo while also revealing dynamic morphogenetic movements displayed by individual mesodermal subtypes. Because none of the mesoderm examined above produced the pancreatic mesenchyme that condenses around the induced bud to support exocrine and endocrine differentiation, we also sought to identify the mesodermal origins of this mesenchyme. We identify a portion of the coelomic mesoderm that contributes to the condensed pancreatic mesenchyme. In conclusion, we identify a portion of the notochord as a likely source of the signals required to induce and maintain the early dorsal pancreas bud, demonstrate that the coelomic mesothelium contributes to the dorsal and ventral pancreatic mesenchyme, and provide insight into the dynamic morphological rearrangements of mesoderm-derived tissues during early organogenesis stages of mammalian development.}, } @article {pmid29329720, year = {2018}, author = {Paulsen, T and Kumar, P and Koseoglu, MM and Dutta, A}, title = {Discoveries of Extrachromosomal Circles of DNA in Normal and Tumor Cells.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {270-278}, pmid = {29329720}, issn = {0168-9525}, support = {R01 CA060499/CA/NCI NIH HHS/United States ; R01 CA166054/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Chromosomes, Human/chemistry/metabolism ; DNA, Chloroplast/chemistry/genetics/metabolism ; DNA, Circular/chemistry/*genetics/metabolism ; DNA, Kinetoplast/chemistry/genetics/metabolism ; DNA, Mitochondrial/chemistry/*genetics/metabolism ; DNA, Neoplasm/chemistry/*genetics/metabolism ; Eukaryotic Cells/chemistry/metabolism ; Humans ; Kinetoplastida/genetics/metabolism ; Neoplasms/*genetics/metabolism/pathology ; Neoplastic Cells, Circulating/*chemistry/metabolism ; Plants/genetics/metabolism ; Plasmids/chemistry/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Telomere/chemistry/metabolism ; }, abstract = {While the vast majority of cellular DNA in eukaryotes is contained in long linear strands in chromosomes, we have long recognized some exceptions like mitochondrial DNA, plasmids in yeasts, and double minutes (DMs) in cancer cells where the DNA is present in extrachromosomal circles. In addition, specialized extrachromosomal circles of DNA (eccDNA) have been noted to arise from repetitive genomic sequences like telomeric DNA or rDNA. Recently eccDNA arising from unique (nonrepetitive) DNA have been discovered in normal and malignant cells, raising interesting questions about their biogenesis, function and clinical utility. Here, we review recent results and future directions of inquiry on these new forms of eccDNA.}, } @article {pmid29329719, year = {2018}, author = {Carey, KT and Wickramasinghe, VO}, title = {Regulatory Potential of the RNA Processing Machinery: Implications for Human Disease.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {4}, pages = {279-290}, doi = {10.1016/j.tig.2017.12.012}, pmid = {29329719}, issn = {0168-9525}, mesh = {Active Transport, Cell Nucleus ; Carcinogenesis/*genetics/metabolism/pathology ; Cytoplasm/genetics/metabolism ; DNA Damage ; Eukaryotic Cells/metabolism ; Genome, Human ; Genomic Instability ; Humans ; Neoplasms/*genetics/metabolism/pathology ; Neurodegenerative Diseases/*genetics/metabolism/pathology ; *RNA Splicing ; RNA, Messenger/*genetics/metabolism ; RNA, Small Nuclear/genetics/metabolism ; Spliceosomes/*genetics/metabolism ; }, abstract = {Splicing and nuclear export of mRNA are critical steps in the gene expression pathway. While RNA processing factors can perform general, essential functions for intron removal and bulk export of mRNA, emerging evidence highlights that the core RNA splicing and export machineries also display regulatory potential. Here, we discuss recent insights into how this regulatory potential can selectively alter gene expression and regulate important biological processes. We also highlight the participation of RNA processing pathways in the cellular response to DNA damage at multiple levels. These findings have important implications for the contribution of selective mRNA processing and export to the development of human cancers and neurodegenerative disorders.}, } @article {pmid29329603, year = {2018}, author = {da Mota E Silva, MS and da Glória da Costa Carvalho, M and Moreira, JC and de Oliveira Barreto, E and de Farias, KF and Nascimento, CA and da Silva, FMN and de Andrade, TG and Luiz, RR and de Moura Neto, RS and Ribeiro, FL}, title = {Green Tobacco Sickness among Brazilian farm workers and genetic polymorphisms.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {20}, pmid = {29329603}, issn = {1756-0500}, support = {402311/2010-8//The National Counsel of Technological and Scientific Development - CNPq/ ; PROEX-311/2008//Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES/ ; }, mesh = {Adult ; Aged ; Agricultural Workers' Diseases/*epidemiology/*genetics ; Brazil/epidemiology ; Female ; Humans ; Male ; Middle Aged ; Nicotine/*poisoning ; Occupational Exposure/*statistics & numerical data ; Polymorphism, Genetic ; Prevalence ; Sex Factors ; Skin Absorption ; Tobacco/*poisoning ; Tobacco Industry/*statistics & numerical data ; Young Adult ; }, abstract = {OBJECTIVE: Green Tobacco Sickness (GTS) is an occupational illness caused by dermal absorption of nicotine from tobacco leaves. It affects thousands of farm workers worldwide. Brazil is the second tobacco producer in the world; despite this, there are few studies on GTS among Brazilian harvesters. This study aimed to determine the prevalence of GTS among a population of tobacco workers from a producing area in northeastern Brazil and investigate whether the occurrence of the disease was influenced by factors such age, gender and smoking status. In addition, it was investigated if there was association between the onset of GTS and genetic polymorphisms in genes that encode some detoxification enzymes. A semi-structured questionnaire was used to collect demographic, behavioral and occupational data from the referred workers. Polymorphisms were tested through the Polymerase Chain Reaction technique.

RESULTS: The total prevalence of GTS found was 56.9%, with a significant difference between genders (71.7% for women and 35.3% for men, p < 0.0001). No association was identified between the investigated polymorphisms and GTS. This study confirms the occurrence of GTS among tobacco harvesters in Brazil with high prevalence. The investigation suggests the need to take preventive measures to protect tobacco workers against this disease.}, } @article {pmid29329601, year = {2018}, author = {Khafizova, G and Dobrynin, P and Polev, D and Matveeva, T}, title = {Nicotiana glauca whole-genome investigation for cT-DNA study.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {18}, pmid = {29329601}, issn = {1756-0500}, support = {16-16-10010//Russian Science Foundation/ ; 1.52.1647.2016//Saint Petersburg State University/ ; }, mesh = {DNA, Bacterial/*genetics ; Gene Transfer, Horizontal/*genetics ; Genome, Plant/*genetics ; High-Throughput Nucleotide Sequencing/*methods ; Sequence Analysis, DNA/*methods ; Tobacco/*genetics ; }, abstract = {OBJECTIVE: Nicotiana glauca (tree tobacco) is a naturally transgenic plant, containing sequences acquired from Agrobacterium rhizogenes by horizontal gene transfer. Besides, N. glauca contains a wide profile of alkaloids of medical interest.

DATA DESCRIPTION: We report a high-depth sequencing and de novo assembly of N. glauca full genome and analysis of genome elements with bacterial origin. The draft genome assembly is 3.2 Gb, with N50 size of 31.1 kbp. Comparative analysis confirmed the presence of single, previously described gT insertion. No evidence was acquired to support idea of multiple T-DNA insertions in the N. glauca genome. Our data is the first comprehensive de novo assembly of tree tobacco and provide valuable information for researches in pharmacological and in phylogenetic fields.}, } @article {pmid29329600, year = {2018}, author = {Owolabi, EO and Ter Goon, D and Adeniyi, OV and Ajayi, AI}, title = {Optimal waist circumference cut-off points for predicting metabolic syndrome among low-income black South African adults.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {22}, pmid = {29329600}, issn = {1756-0500}, support = {P838//Health and Welfare Sector Education and Training Authority/ ; SFH15071612676//National Research Foundation/ ; }, mesh = {Adolescent ; Adult ; African Continental Ancestry Group/*ethnology ; Aged ; Female ; Humans ; Male ; Metabolic Syndrome/*diagnosis ; Middle Aged ; Poverty/*ethnology ; Reference Values ; South Africa/ethnology ; Waist Circumference/*ethnology ; Young Adult ; }, abstract = {OBJECTIVE: Waist circumference has been identified as one of the strongest predictive tool for metabolic syndrome. This study determines the optimal cut-off point of waist circumference for metabolic syndrome among low-income earning South African black population, in Eastern Cape, South Africa. The optimal waist circumference cut-off point was determined through receiver operating characteristics analysis using the maximum Youden index.

RESULTS: Among men, waist circumference at a cut-off value of 95.25 cm yielded the highest Youden index of 0.773 (sensitivity = 98%, specificity = 79%, area under curve 0.893). For women, waist circumference of 89.45 cm yielded the highest Youden index of 0.339 (sensitivity = 88%, specificity = 46%, area under curve 0.713). The prevalence of metabolic syndrome among men, women and both sexes using the new cut-off points were: 17.8, 20.8 and 17.7%, respectively, compared to; 15.6, 24.8 and 21.8%, using the traditional cut-off values of 94 and 80 cm for men and women, respectively. The traditional waist circumference value slightly under-estimated the prevalence of metabolic syndrome among men and over-estimated among women and the overall population. A specific waist circumference cut-off point for South African blacks is needed for correct identification of the metabolic state of the populace in order to develop appropriate interventions.}, } @article {pmid29329598, year = {2018}, author = {Mawalla, B and Yuan, X and Luo, X and Chalya, PL}, title = {Treatment outcome of anti-angiogenesis through VEGF-pathway in the management of gastric cancer: a systematic review of phase II and III clinical trials.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {21}, pmid = {29329598}, issn = {1756-0500}, mesh = {Angiogenesis Inhibitors/*pharmacology ; *Clinical Trials, Phase II as Topic ; *Clinical Trials, Phase III as Topic ; Humans ; *Outcome Assessment (Health Care) ; Stomach Neoplasms/*drug therapy ; Vascular Endothelial Growth Factors/*antagonists & inhibitors ; }, abstract = {OBJECTIVES: Advanced gastric cancer poses a therapeutic challenge worldwide. In randomised clinical trials, anti-VEGF has been reported as an essential agent for the treatment of advanced gastric cancer. This review aims at assessing the treatment outcome of anti-angiogenesis therapy through the VEGF pathway in the management of patients with advanced gastric cancer.

RESULTS: During this review, 38 clinical trials were identified. Of these, 30 clinical trials were excluded, leaving eight trials of phase II and III. Ramucirumab, as a second line treatment of advanced gastric cancer, decreases the risk of disease progression (37-52%) and death (19-22%). Compare ramucirumab and bevacizumab in combination with traditional chemotherapy; ramucirumab has shown to improve progression-free survival and overall survival. Apatinib tyrosine kinase inhibitor combined with traditional chemotherapy has shown to improve overall response rate and progression-free survival with marginal improvements in overall survival. Chemotherapy, in combination with anti-VEGF drugs, in the management of advanced gastric cancer significantly improves the outcome of overall response rate, progression-free survival and overall survival when compared to chemotherapy alone. Therefore, we recommend that anti-VEGF drugs are the drugs of choice in the management of patients with advanced gastric cancer.}, } @article {pmid29329597, year = {2018}, author = {Nagata, S and Seki, Y and Shibuya, T and Yokoo, M and Murata, T and Hiramatsu, Y and Yamada, F and Ibuki, H and Minamitani, N and Yoshinaga, N and Kusunoki, M and Inada, Y and Kawasoe, N and Adachi, S and Oshiro, K and Matsuzawa, D and Hirano, Y and Yoshimura, K and Nakazato, M and Iyo, M and Nakagawa, A and Shimizu, E}, title = {Does cognitive behavioral therapy alter mental defeat and cognitive flexibility in patients with panic disorder?.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {23}, pmid = {29329597}, issn = {1756-0500}, support = {JP15H06090//JSPS KAKENHI Grant/ ; }, mesh = {Adult ; Aged ; Cognitive Behavioral Therapy/*methods ; Executive Function/*physiology ; Female ; Humans ; Male ; Middle Aged ; *Outcome Assessment (Health Care) ; Panic Disorder/*physiopathology/*therapy ; *Self Concept ; Thinking/*physiology ; Young Adult ; }, abstract = {OBJECTIVE: Mental defeat and cognitive flexibility have been studied as explanatory factors for depression and posttraumatic stress disorder. This study examined mental defeat and cognitive flexibility scores in patients with panic disorder (PD) before and after cognitive behavioral therapy (CBT), and compared them to those of a gender- and age-matched healthy control group.

RESULTS: Patients with PD (n = 15) received 16 weekly individual CBT sessions, and the control group (n = 35) received no treatment. Patients completed the Mental Defeat Scale and the Cognitive Flexibility Scale before the intervention, following eight CBT sessions, and following 16 CBT sessions, while the control group did so only prior to receiving CBT (baseline). The patients' pre-CBT Mental Defeat and Cognitive Flexibility Scale scores were significantly higher on the Mental Defeat Scale and lower on the Cognitive Flexibility Scale than those of the control group participants were. In addition, the average Mental Defeat Scale scores of the patients decreased significantly, from 22.2 to 12.4, while their average Cognitive Flexibility Scale scores increased significantly, from 42.8 to 49.5. These results suggest that CBT can reduce mental defeat and increase cognitive flexibility in patients with PD Trial registration The study was registered retrospectively in the national UMIN Clinical Trials Registry on June 10, 2016 (registration ID: UMIN000022693).}, } @article {pmid29329594, year = {2018}, author = {Robinson, JM and Henderson, WA}, title = {Modelling the structure of a ceRNA-theoretical, bipartite microRNA-mRNA interaction network regulating intestinal epithelial cellular pathways using R programming.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {19}, pmid = {29329594}, issn = {1756-0500}, mesh = {Adherens Junctions/*metabolism ; Databases, Genetic ; Epithelial Cells/*metabolism ; Humans ; Intestinal Mucosa/*metabolism ; MicroRNAs/*metabolism ; *Models, Genetic ; RNA, Messenger/*metabolism ; *Signal Transduction ; Tight Junctions/*metabolism ; }, abstract = {OBJECTIVE: We report a method using functional-molecular databases and network modelling to identify hypothetical mRNA-miRNA interaction networks regulating intestinal epithelial barrier function. The model forms a data-analysis component of our cell culture experiments, which produce RNA expression data from Nanostring Technologies nCounter® system. The epithelial tight-junction (TJ) and actin cytoskeleton interact as molecular components of the intestinal epithelial barrier. Upstream regulation of TJ-cytoskeleton interaction is effected by the Rac/Rock/Rho signaling pathway and other associated pathways which may be activated or suppressed by extracellular signaling from growth factors, hormones, and immune receptors. Pathway activations affect epithelial homeostasis, contributing to degradation of the epithelial barrier associated with osmotic dysregulation, inflammation, and tumor development. The complexity underlying miRNA-mRNA interaction networks represents a roadblock for prediction and validation of competing-endogenous RNA network function.

RESULTS: We developed a network model to identify hypothetical co-regulatory motifs in a miRNA-mRNA interaction network related to epithelial function. A mRNA-miRNA interaction list was generated using KEGG and miRWalk2.0 databases. R-code was developed to quantify and visualize inherent network structures. We identified a sub-network with a high number of shared, targeting miRNAs, of genes associated with cellular proliferation and cancer, including c-MYC and Cyclin D.}, } @article {pmid29329541, year = {2018}, author = {Peñarando, J and López-Sánchez, LM and Mena, R and Guil-Luna, S and Conde, F and Hernández, V and Toledano, M and Gudiño, V and Raponi, M and Billard, C and Villar, C and Díaz, C and Gómez-Barbadillo, J and De la Haba-Rodríguez, J and Myant, K and Aranda, E and Rodríguez-Ariza, A}, title = {A role for endothelial nitric oxide synthase in intestinal stem cell proliferation and mesenchymal colorectal cancer.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {3}, pmid = {29329541}, issn = {1741-7007}, abstract = {BACKGROUND: Nitric oxide (NO) has been highlighted as an important agent in cancer-related events. Although the inducible nitric oxide synthase (iNOS) isoform has received most attention, recent studies in the literature indicate that the endothelial isoenzyme (eNOS) can also modulate different tumor processes including resistance, angiogenesis, invasion, and metastasis. However, the role of eNOS in cancer stem cell (CSC) biology and mesenchymal tumors is unknown.

RESULTS: Here, we show that eNOS was significantly upregulated in VilCre ERT2 Apc fl/+ and VilCre ERT2 Apc fl/fl mouse intestinal tissue, with intense immunostaining in hyperproliferative crypts. Similarly, the more invasive VilCre ERT2 Apc fl/+ Pten fl/+ mouse model showed an overexpression of eNOS in intestinal tumors whereas this isoform was not expressed in normal tissue. However, none of the three models showed iNOS expression. Notably, when 40 human colorectal tumors were classified into different clinically relevant molecular subtypes, high eNOS expression was found in the poor relapse-free and overall survival mesenchymal subtype, whereas iNOS was absent. Furthermore, Apc fl/fl organoids overexpressed eNOS compared with wild-type organoids and NO depletion with the scavenger carboxy-PTIO (c-PTIO) decreased the proliferation and the expression of stem-cell markers, such as Lgr5, Troy, Vav3, and Slc14a1, in these intestinal organoids. Moreover, specific NO depletion also decreased the expression of CSC-related proteins in human colorectal cancer cells such as β-catenin and Bmi1, impairing the CSC phenotype. To rule out the contribution of iNOS in this effect, we established an iNOS-knockdown colorectal cancer cell line. NO-depleted cells showed a decreased capacity to form tumors and c-PTIO treatment in vivo showed an antitumoral effect in a xenograft mouse model.

CONCLUSION: Our data support that eNOS upregulation occurs after Apc loss, emerging as an unexpected potential new target in poor-prognosis mesenchymal colorectal tumors, where NO scavenging could represent an interesting therapeutic alternative to targeting the CSC subpopulation.}, } @article {pmid29329524, year = {2018}, author = {Palacios-Gimenez, OM and Milani, D and Lemos, B and Castillo, ER and Martí, DA and Ramos, E and Martins, C and Cabral-de-Mello, DC}, title = {Uncovering the evolutionary history of neo-XY sex chromosomes in the grasshopper Ronderosia bergii (Orthoptera, Melanoplinae) through satellite DNA analysis.}, journal = {BMC evolutionary biology}, volume = {18}, number = {1}, pages = {2}, pmid = {29329524}, issn = {1471-2148}, support = {2014/11763-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/International ; }, mesh = {Animals ; DNA, Satellite/*genetics ; *Evolution, Molecular ; Female ; Grasshoppers/*genetics ; In Situ Hybridization, Fluorescence ; Male ; Metaphase/genetics ; *Sequence Analysis, DNA ; X Chromosome/*genetics ; Y Chromosome/*genetics ; }, abstract = {BACKGROUND: Neo-sex chromosome systems arose independently multiple times in evolution, presenting the remarkable characteristic of repetitive DNAs accumulation. Among grasshoppers, occurrence of neo-XY was repeatedly noticed in Melanoplinae. Here we analyzed the most abundant tandem repeats of R. bergii (2n = 22, neo-XY♂) using deep Illumina sequencing and graph-based clustering in order to address the neo-sex chromosomes evolution.

RESULTS: The analyses revealed ten families of satDNAs comprising about ~1% of the male genome, which occupied mainly C-positive regions of autosomes. Regarding the sex chromosomes, satDNAs were recorded within centromeric or interstitial regions of the neo-X chromosome and four satDNAs occurred in the neo-Y, two of them being exclusive (Rber248 and Rber299). Using a combination of probes we uncovered five well-defined cytological variants for neo-Y, originated by multiple paracentric inversions and satDNA amplification, besides fragmented neo-Y. These neo-Y variants were distinct in frequency between embryos and adult males.

CONCLUSIONS: The genomic data together with cytogenetic mapping enabled us to better understand the neo-sex chromosome dynamics in grasshoppers, reinforcing differentiation of neo-X and neo-Y and revealing the occurrence of multiple additional rearrangements involved in the neo-Y evolution of R. bergii. We discussed the possible causes that led to differences in frequency for the neo-Y variants between embryos and adults. Finally we hypothesize about the role of DNA satellites in R. bergii as well as putative historical events involved in the evolution of the R. bergii neo-XY.}, } @article {pmid29329522, year = {2018}, author = {Chiara, M and Placido, A and Picardi, E and Ceci, LR and Horner, DS and Pesole, G}, title = {A-GAME: improving the assembly of pooled functional metagenomics sequence data.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {44}, pmid = {29329522}, issn = {1471-2164}, support = {H2020-BG-2014-2, GA 634486//H2020 European Research Council/International ; H2020-INFRADEV-1-2014-1, GA 654008//H2020 European Research Council/International ; H2020-INFRADEV-1-2015-1, GA 676559//H2020 European Research Council/International ; }, mesh = {Computational Biology/methods ; Databases, Genetic ; *Gene Library ; *Genome, Microbial ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; *Internet ; Metagenomics/*methods ; Molecular Sequence Annotation ; *Software ; Workflow ; }, abstract = {BACKGROUND: Expression screening of environmental DNA (eDNA) libraries is a popular approach for the identification and characterization of novel microbial enzymes with promising biotechnological properties. In such "functional metagenomics" experiments, inserts, selected on the basis of activity assays, are sequenced with high throughput sequencing technologies. Assembly is followed by gene prediction, annotation and identification of candidate genes that are subsequently evaluated for biotechnological applications.

RESULTS: Here we present A-GAME (A GAlaxy suite for functional MEtagenomics), a web service incorporating state of the art tools and workflows for the analysis of eDNA sequence data. We illustrate the potential of A-GAME workflows using real functional metagenomics data, showing that they outperform alternative metagenomics assemblers. Dedicated tools available in A-GAME allow efficient analysis of pooled libraries and rapid identification of candidate genes, reducing sequencing costs and saving the need for laborious manual annotation.

CONCLUSION: In conclusion, we believe A-GAME will constitute a valuable resource for the functional metagenomics community. A-GAME is publicly available at http://beaconlab.it/agame.}, } @article {pmid29329517, year = {2018}, author = {Chung, PJ and Jung, H and Choi, YD and Kim, JK}, title = {Genome-wide analyses of direct target genes of four rice NAC-domain transcription factors involved in drought tolerance.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {40}, pmid = {29329517}, issn = {1471-2164}, support = {NRF-2013R1A6A3A04060627//the National Research Foundation of Korea/International ; PJ011829012016//the Rural Development Administration under the Next-Generation Biogreen 21 program/International ; }, mesh = {Chromatin Immunoprecipitation/methods ; *Droughts ; *Gene Expression Regulation, Plant ; Genome-Wide Association Study/*methods ; Oryza/*genetics/growth & development/metabolism ; Plant Proteins/genetics/*metabolism ; Plants, Genetically Modified/*genetics/growth & development/metabolism ; Protein Domains ; Sequence Analysis, RNA/methods ; Stress, Physiological ; Transcription Factors/genetics/*metabolism ; }, abstract = {BACKGROUND: Plant stress responses and mechanisms determining tolerance are controlled by diverse sets of genes. Transcription factors (TFs) have been implicated in conferring drought tolerance under drought stress conditions, and the identification of their target genes can elucidate molecular regulatory networks that orchestrate tolerance mechanisms.

RESULTS: We generated transgenic rice plants overexpressing the 4 rice TFs, OsNAC5, 6, 9, and 10, under the control of the root-specific RCc3 promoter. We showed that they were tolerant to drought stress with reduced loss of grain yield under drought conditions compared with wild type plants. To understand the molecular mechanisms underlying this tolerance, we here performed chromatin immunoprecipitation (ChIP)-Seq and RNA-Seq analyses to identify the direct target genes of the OsNAC proteins using the RCc3:6MYC-OsNAC expressing roots. A total of 475 binding loci for the 4 OsNAC proteins were identified by cross-referencing their binding to promoter regions and the expression levels of the corresponding genes. The binding loci were distributed among the promoter regions of 391 target genes that were directly up-regulated by one of the OsNAC proteins in four RCc3:6MYC-OsNAC transgenic lines. Based on gene ontology (GO) analysis, the direct target genes were related to transmembrane/transporter activity, vesicle, plant hormones, carbohydrate metabolism, and TFs. The direct targets of each OsNAC range from 4.0-8.7% of the total number of up-regulated genes found in the RNA-Seq data sets. Thus, each OsNAC up-regulates a set of direct target genes that alter root system architecture in the RCc3:OsNAC plants to confer drought tolerance. Our results provide a valuable resource for functional dissection of the molecular mechanisms of drought tolerance.

CONCLUSIONS: Many of the target genes, including transmembrane/transporter, vesicle related, auxin/hormone related, carbohydrate metabolic processes, and transcription factor genes, that are up-regulated by OsNACs act as the cellular components which would alter the root architectures of RCc3:OsNACs for drought tolerance.}, } @article {pmid29329439, year = {2018}, author = {Lee, SJ and Kong, M and Harrison, P and Hijri, M}, title = {Conserved Proteins of the RNA Interference System in the Arbuscular Mycorrhizal Fungus Rhizoglomus irregulare Provide New Insight into the Evolutionary History of Glomeromycota.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {328-343}, pmid = {29329439}, issn = {1759-6653}, mesh = {Amino Acid Sequence ; Cyanobacteria/chemistry/genetics ; *Evolution, Molecular ; Fungal Proteins/chemistry/genetics ; Gene Transfer, Horizontal ; Genes, Fungal ; Glomeromycota/chemistry/*genetics ; Mycorrhizae/chemistry/*genetics ; *Phylogeny ; RNA Interference ; Ribonuclease III/chemistry/genetics ; Sequence Alignment ; Symbiosis ; Transcriptome ; }, abstract = {Horizontal gene transfer (HGT) is an important mechanism in the evolution of many living organisms particularly in Prokaryotes where genes are frequently dispersed between taxa. Although, HGT has been reported in Eukaryotes, its accumulative effect and its frequency has been questioned. Arbuscular mycorrhizal fungi (AMF) are an early diverged fungal lineage belonging to phylum Glomeromycota, whose phylogenetic position is still under debate. The history of AMF and land plant symbiosis dates back to at least 460 Ma. However, Glomeromycota are estimated to have emerged much earlier than land plants. In this study, we surveyed genomic and transcriptomic data of the model arbuscular mycorrhizal fungus Rhizoglomus irregulare (synonym Rhizophagus irregularis) and its relatives to search for evidence of HGT that occurred during AMF evolution. Surprisingly, we found a signature of putative HGT of class I ribonuclease III protein-coding genes that occurred from autotrophic cyanobacteria genomes to R. irregulare. At least one of two HGTs was conserved among AMF species with high levels of sequence similarity. Previously, an example of intimate symbiosis between AM fungus and cyanobacteria was reported in the literature. Ribonuclease III family enzymes are important in small RNA regulation in Fungi together with two additional core proteins (Argonaute/piwi and RdRP). The eukaryotic RNA interference system found in AMF was conserved and showed homology with high sequence similarity in Mucoromycotina, a group of fungi closely related to Glomeromycota. Prior to this analysis, class I ribonuclease III has not been identified in any eukaryotes. Our results indicate that a unique acquisition of class I ribonuclease III in AMF is due to a HGT event that occurred from cyanobacteria to Glomeromycota, at the latest before the divergence of the two Glomeromycota orders Diversisporales and Glomerales.}, } @article {pmid29329426, year = {2018}, author = {Mitov, V and Stadler, T}, title = {A Practical Guide to Estimating the Heritability of Pathogen Traits.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29329426}, issn = {1537-1719}, abstract = {Pathogen traits, such as the virulence of an infection, can vary significantly between patients. A major challenge is to measure the extent to which genetic differences between infecting strains explain the observed variation of the trait. This is quantified by the trait's broad-sense heritability, H2. A recent discrepancy between estimates of the heritability of HIV-virulence has opened a debate on the estimators' accuracy. Here, we show that the discrepancy originates from model limitations and important lifecycle differences between sexually reproducing organisms and transmittable pathogens. In particular, current quantitative genetics methods, such as donor-recipient regression (DR) of surveyed serodiscordant couples and the phylogenetic mixed model (PMM), are prone to underestimate H2, because they neglect or do not fit to the loss of resemblance between transmission partners caused by within-host evolution. In a phylogenetic analysis of 8,483 HIV patients from the UK, we show that the phenotypic correlation between transmission partners decays with the amount of within-host evolution of the virus. We reproduce this pattern in toy-model simulations and show that a phylogenetic Ornstein-Uhlenbeck model (POUMM) outperforms the PMM in capturing this correlation pattern and in quantifying H2. In particular, we show that POUMM outperforms PMM even in simulations without selection - as it captures the mentioned correlation pattern - which has not been appreciated until now. By cross-validating the POUMM estimates with ANOVA on closest phylogenetic pairs (ANOVA-CPP), we obtain H2≈0.2, meaning about 20% of the variation in HIV-virulence is explained by the virus genome both for European and African data.}, } @article {pmid29329419, year = {2018}, author = {Whittington, AC and Mason, AJ and Rokyta, DR}, title = {A Single Mutation Unlocks Cascading Exaptations in the Origin of a Potent Pitviper Neurotoxin.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {887-898}, doi = {10.1093/molbev/msx334}, pmid = {29329419}, issn = {1537-1719}, abstract = {Evolutionary innovations and complex phenotypes seemingly require an improbable amount of genetic change to evolve. Rattlesnakes display two dramatically different venom phenotypes. Type I venoms are hemorrhagic with low systemic toxicity and high expression of tissue-destroying snake venom metalloproteinases. Type II venoms are highly neurotoxic and lack snake venom metalloproteinase expression and associated hemorrhagic activity. This dichotomy hinges on Mojave toxin (MTx), a phospholipase A2 (PLA2) based β-neurotoxin expressed in Type II venoms. MTx is comprised of a nontoxic acidic subunit that undergoes extensive proteolytic processing and allosterically regulates activity of a neurotoxic basic subunit. Evolution of the acidic subunit presents an evolutionary challenge because the need for high expression of a nontoxic venom component and the proteolytic machinery required for processing suggests genetic changes of seemingly little immediate benefit to fitness. We showed that MTx evolved through a cascading series of exaptations unlocked by a single nucleotide change. The evolution of one new cleavage site in the acidic subunit unmasked buried cleavage sites already present in ancestral PLA2s, enabling proteolytic processing. Snake venom serine proteases, already present in the venom to disrupt prey hemostasis, possess the requisite specificities for MTx acidic subunit proteolysis. The dimerization interface between MTx subunits evolved by exploiting a latent, but masked, hydrophobic interaction between ancestral PLA2s. The evolution of MTx through exaptation of existing functional and structural features suggests complex phenotypes that depend on evolutionary innovations can arise from minimal genetic change enabled by prior evolution.}, } @article {pmid29328957, year = {2018}, author = {Heaver, SL and Johnson, EL and Ley, RE}, title = {Sphingolipids in host-microbial interactions.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {92-99}, doi = {10.1016/j.mib.2017.12.011}, pmid = {29328957}, issn = {1879-0364}, mesh = {Animals ; Bacteria/chemistry/*metabolism ; Eukaryota/chemistry/metabolism ; Host Microbial Interactions/*physiology ; Humans ; Mice ; *Microbial Interactions ; Signal Transduction ; Sphingolipids/biosynthesis/chemistry/*metabolism ; }, abstract = {Sphingolipids, a lipid class characterized by a long-chain amino alcohol backbone, serve vital structural and signaling roles in eukaryotes. Though eukaryotes produce sphingolipids, this capacity is phylogenetically highly restricted in Bacteria. Intriguingly, bacterial species commonly associated in high abundance with eukaryotic hosts include sphingolipid producers, such as the Bacteroidetes in the mammalian gut. To date, a role for bacterial sphingolipids in immune system maturation has been described, but their fate and impact in host physiology and metabolism remain to be elucidated. The structural conservation of bacterial sphingolipids with those produced by their mammalian hosts offer clues about which aspects of mammalian biology may be modulated by these intriguing lipids.}, } @article {pmid29328784, year = {2018}, author = {Neri, D and Lerner, RA}, title = {DNA-Encoded Chemical Libraries: A Selection System Based on Endowing Organic Compounds with Amplifiable Information.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {479-502}, pmid = {29328784}, issn = {1545-4509}, support = {163479//Swiss National Science Foundation/Switzerland ; 670603//European Research Council/International ; }, abstract = {The discovery of organic ligands that bind specifically to proteins is a central problem in chemistry, biology, and the biomedical sciences. The encoding of individual organic molecules with distinctive DNA tags, serving as amplifiable identification bar codes, allows the construction and screening of combinatorial libraries of unprecedented size, thus facilitating the discovery of ligands to many different protein targets. Fundamentally, one links powers of genetics and chemical synthesis. After the initial description of DNA-encoded chemical libraries in 1992, several experimental embodiments of the technology have been reduced to practice. This review provides a historical account of important milestones in the development of DNA-encoded chemical libraries, a survey of relevant ongoing research activities, and a glimpse into the future.}, } @article {pmid29328783, year = {2018}, author = {Willis, IM and Moir, RD}, title = {Signaling to and from the RNA Polymerase III Transcription and Processing Machinery.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {75-100}, pmid = {29328783}, issn = {1545-4509}, support = {R01 GM120358/GM/NIGMS NIH HHS/United States ; }, abstract = {RNA polymerase (Pol) III has a specialized role in transcribing the most abundant RNAs in eukaryotic cells, transfer RNAs (tRNAs), along with other ubiquitous small noncoding RNAs, many of which have functions related to the ribosome and protein synthesis. The high energetic cost of producing these RNAs and their central role in protein synthesis underlie the robust regulation of Pol III transcription in response to nutrients and stress by growth regulatory pathways. Downstream of Pol III, signaling impacts posttranscriptional processes affecting tRNA function in translation and tRNA cleavage into smaller fragments that are increasingly attributed with novel cellular activities. In this review, we consider how nutrients and stress control Pol III transcription via its factors and its negative regulator, Maf1. We highlight recent work showing that the composition of the tRNA population and the function of individual tRNAs is dynamically controlled and that unrestrained Pol III transcription can reprogram central metabolic pathways.}, } @article {pmid29327508, year = {2018}, author = {Perez-Sepulveda, B and Pitt, F and N'Guyen, AN and Ratin, M and Garczarek, L and Millard, A and Scanlan, DJ}, title = {Relative stability of ploidy in a marine Synechococcus across various growth conditions.}, journal = {Environmental microbiology reports}, volume = {10}, number = {4}, pages = {428-432}, doi = {10.1111/1758-2229.12614}, pmid = {29327508}, issn = {1758-2229}, abstract = {Marine picocyanobacteria of the genus Synechococcus are ubiquitous phototrophs in oceanic systems. Consistent with these organisms occupying vast tracts of the nutrient impoverished ocean, most marine Synechococcus so far studied are monoploid, i.e., contain a single chromosome copy. The exception is the oligoploid strain Synechococcus sp. WH7803, which on average possesses around 4 chromosome copies. Here, we set out to understand the role of resource availability (through nutrient deplete growth) and physical stressors (UV, exposure to low and high temperature) in regulating ploidy level in this strain. Using qPCR to assay ploidy status we demonstrate the relative stability of chromosome copy number in Synechococcus sp. WH7803. Such robustness in maintaining an oligoploid status even under nutrient and physical stress is indicative of a fundamental role, perhaps facilitating recombination of damaged DNA regions as a result of prolonged exposure to oxidative stress, or allowing added flexibility in gene expression via possessing multiple alleles.}, } @article {pmid29327481, year = {2018}, author = {Bahram, M and Vanderpool, D and Pent, M and Hiltunen, M and Ryberg, M}, title = {The genome and microbiome of a dikaryotic fungus (Inocybe terrigena, Inocybaceae) revealed by metagenomics.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {155-166}, doi = {10.1111/1758-2229.12612}, pmid = {29327481}, issn = {1758-2229}, mesh = {Agaricales/classification/*genetics/isolation & purification/physiology ; Bacteria/classification/genetics/*isolation & purification ; Bacterial Physiological Phenomena ; Fruiting Bodies, Fungal/classification/genetics/isolation & purification/physiology ; Genome, Fungal ; Metagenomics ; *Microbiota ; Phylogeny ; Symbiosis ; }, abstract = {Recent advances in molecular methods have increased our understanding of various fungal symbioses. However, little is known about genomic and microbiome features of most uncultured symbiotic fungal clades. Here, we analysed the genome and microbiome of Inocybaceae (Agaricales, Basidiomycota), a largely uncultured ectomycorrhizal clade known to form symbiotic associations with a wide variety of plant species. We used metagenomic sequencing and assembly of dikaryotic fruiting-body tissues from Inocybe terrigena (Fr.) Kuyper, to classify fungal and bacterial genomic sequences, and obtained a nearly complete fungal genome containing 93% of core eukaryotic genes. Comparative genomics reveals that I. terrigena is more similar to ectomycorrhizal and brown rot fungi than to white rot fungi. The reduction in lignin degradation capacity has been independent from and significantly faster than in closely related ectomycorrhizal clades supporting that ectomycorrhizal symbiosis evolved independently in Inocybe. The microbiome of I. terrigena fruiting-bodies includes bacteria with known symbiotic functions in other fungal and non-fungal host environments, suggesting potential symbiotic functions of these bacteria in fungal tissues regardless of habitat conditions. Our study demonstrates the usefulness of direct metagenomics analysis of fruiting-body tissues for characterizing fungal genomes and microbiome.}, } @article {pmid29327471, year = {2018}, author = {Conthe, M and Kuenen, JG and Kleerebezem, R and van Loosdrecht, MCM}, title = {Exploring microbial N2 O reduction: a continuous enrichment in nitrogen free medium.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {102-107}, doi = {10.1111/1758-2229.12615}, pmid = {29327471}, issn = {1758-2229}, abstract = {N2 O is a potent greenhouse gas, but also a potent electron acceptor. In search of thermodynamically favourable - yet undescribed - metabolic pathways involving N2 O reduction, we set up a continuous microbial enrichment, inoculated with activated sludge, fed with N2 O as the sole electron acceptor and acetate as an electron donor. A nitrogen-free mineral medium was used with the intention of creating a selective pressure towards organisms that would use N2 O directly as source of nitrogen for cell synthesis. Instead, we obtained a culture dominated by microorganisms of the Rhodocyclaceae family growing by N2 O reduction to N2 coupled to N2 fixation. Biomass yields of this culture were 40% lower than those of a previously reported culture grown under comparable conditions but with an NH4+-amended medium, as expected from the extra energy expense of N2 fixation. Interestingly, we found no significant difference in yields whether N2 O or acetate was the growth-limiting substrate in the chemostat in contrast to the study with NH4+-amended medium, in which biomass yields were roughly 30% lower during acetate limiting conditions.}, } @article {pmid29327437, year = {2018}, author = {Zhang, CJ and Delgado-Baquerizo, M and Drake, JE and Reich, PB and Tjoelker, MG and Tissue, DT and Wang, JT and He, JZ and Singh, BK}, title = {Intraspecies variation in a widely distributed tree species regulates the responses of soil microbiome to different temperature regimes.}, journal = {Environmental microbiology reports}, volume = {10}, number = {2}, pages = {167-178}, doi = {10.1111/1758-2229.12613}, pmid = {29327437}, issn = {1758-2229}, mesh = {Bacteria/classification/genetics/*isolation & purification ; Ecosystem ; Fungi/classification/genetics/*isolation & purification ; Microbiota ; Soil/chemistry ; *Soil Microbiology ; Temperature ; Trees/classification/*growth & development/microbiology ; }, abstract = {Plant characteristics in different provenances within a single species may vary in response to climate change, which might alter soil microbial communities and ecosystem functions. We conducted a glasshouse experiment and grew seedlings of three provenances (temperate, subtropical and tropical origins) of a tree species (i.e., Eucalyptus tereticornis) at different growth temperatures (18, 21.5, 25, 28.5, 32 and 35.5°C) for 54 days. At the end of the experiment, bacterial and fungal community composition, diversity and abundance were characterized. Measured soil functions included surrogates of microbial respiration, enzyme activities and nutrient cycling. Using Permutation multivariate analysis of variance (PerMANOVA) and network analysis, we found that the identity of tree provenances regulated both structure and function of soil microbiomes. In some cases, tree provenances substantially affected the response of microbial communities to the temperature treatments. For example, we found significant interactions of temperature and tree provenance on bacterial community and relative abundances of Chloroflexi and Zygomycota, and inorganic nitrogen. Microbial abundance was altered in response to increasing temperature, but was not affected by tree provenances. Our study provides novel evidence that even a small variation in biotic components (i.e., intraspecies tree variation) can significantly influence the response of soil microbial community composition and specific soil functions to global warming.}, } @article {pmid29327410, year = {2018}, author = {Eichorst, SA and Trojan, D and Roux, S and Herbold, C and Rattei, T and Woebken, D}, title = {Genomic insights into the Acidobacteria reveal strategies for their success in terrestrial environments.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1041-1063}, pmid = {29327410}, issn = {1462-2920}, abstract = {Members of the phylum Acidobacteria are abundant and ubiquitous across soils. We performed a large-scale comparative genome analysis spanning subdivisions 1, 3, 4, 6, 8 and 23 (n = 24) with the goal to identify features to help explain their prevalence in soils and understand their ecophysiology. Our analysis revealed that bacteriophage integration events along with transposable and mobile elements influenced the structure and plasticity of these genomes. Low- and high-affinity respiratory oxygen reductases were detected in multiple genomes, suggesting the capacity for growing across different oxygen gradients. Among many genomes, the capacity to use a diverse collection of carbohydrates, as well as inorganic and organic nitrogen sources (such as via extracellular peptidases), was detected - both advantageous traits in environments with fluctuating nutrient environments. We also identified multiple soil acidobacteria with the potential to scavenge atmospheric concentrations of H2 , now encompassing mesophilic soil strains within the subdivision 1 and 3, in addition to a previously identified thermophilic strain in subdivision 4. This large-scale acidobacteria genome analysis reveal traits that provide genomic, physiological and metabolic versatility, presumably allowing flexibility and versatility in the challenging and fluctuating soil environment.}, } @article {pmid29326276, year = {2018}, author = {Waller, WH}, title = {My second life as a teacher.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {246}, doi = {10.1126/science.359.6372.246}, pmid = {29326276}, issn = {1095-9203}, } @article {pmid29326275, year = {2018}, author = {Leonardi, I and Li, X and Semon, A and Li, D and Doron, I and Putzel, G and Bar, A and Prieto, D and Rescigno, M and McGovern, DPB and Pla, J and Iliev, ID}, title = {CX3CR1+ mononuclear phagocytes control immunity to intestinal fungi.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {232-236}, pmid = {29326275}, issn = {1095-9203}, support = {R00 DK098310/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; R21 AI123819/AI/NIAID NIH HHS/United States ; K99 DK098310/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; R01 DK113136/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Fungal/biosynthesis/blood ; CX3C Chemokine Receptor 1/*analysis/*genetics ; Candida albicans/growth & development/*immunology ; Colitis/drug therapy/microbiology ; Crohn Disease/genetics/immunology ; Dendritic Cells/immunology ; Gastrointestinal Microbiome/*immunology/physiology ; Humans ; Immunity, Mucosal ; Immunoglobulin G/biosynthesis/blood ; Intestines/immunology/*microbiology ; Mice ; Mutation, Missense ; Mycobiome/*immunology/physiology ; Phagocytes/*immunology/microbiology ; T-Lymphocytes, Regulatory/immunology ; Th17 Cells/immunology ; }, abstract = {Intestinal fungi are an important component of the microbiota, and recent studies have unveiled their potential in modulating host immune homeostasis and inflammatory disease. Nonetheless, the mechanisms governing immunity to gut fungal communities (mycobiota) remain unknown. We identified CX3CR1+ mononuclear phagocytes (MNPs) as being essential for the initiation of innate and adaptive immune responses to intestinal fungi. CX3CR1+ MNPs express antifungal receptors and activate antifungal responses in a Syk-dependent manner. Genetic ablation of CX3CR1+ MNPs in mice led to changes in gut fungal communities and to severe colitis that was rescued by antifungal treatment. In Crohn's disease patients, a missense mutation in the gene encoding CX3CR1 was identified and found to be associated with impaired antifungal responses. These results unravel a role of CX3CR1+ MNPs in mediating interactions between intestinal mycobiota and host immunity at steady state and during inflammatory disease.}, } @article {pmid29326274, year = {2018}, author = {Omer, DB and Maimon, SR and Las, L and Ulanovsky, N}, title = {Social place-cells in the bat hippocampus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {218-224}, doi = {10.1126/science.aao3474}, pmid = {29326274}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Action Potentials ; Animals ; CA1 Region, Hippocampal/cytology/*physiology ; Chiroptera/*physiology ; Flight, Animal ; Male ; Neurons/*physiology ; Place Cells/*physiology ; *Space Perception ; *Spatial Behavior ; Spatial Learning ; }, abstract = {Social animals have to know the spatial positions of conspecifics. However, it is unknown how the position of others is represented in the brain. We designed a spatial observational-learning task, in which an observer bat mimicked a demonstrator bat while we recorded hippocampal dorsal-CA1 neurons from the observer bat. A neuronal subpopulation represented the position of the other bat, in allocentric coordinates. About half of these "social place-cells" represented also the observer's own position-that is, were place cells. The representation of the demonstrator bat did not reflect self-movement or trajectory planning by the observer. Some neurons represented also the position of inanimate moving objects; however, their representation differed from the representation of the demonstrator bat. This suggests a role for hippocampal CA1 neurons in social-spatial cognition.}, } @article {pmid29326273, year = {2018}, author = {Danjo, T and Toyoizumi, T and Fujisawa, S}, title = {Spatial representations of self and other in the hippocampus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {213-218}, doi = {10.1126/science.aao3898}, pmid = {29326273}, issn = {1095-9203}, mesh = {Action Potentials ; Animals ; CA1 Region, Hippocampal/cytology/*physiology ; Male ; Maze Learning ; Models, Biological ; Place Cells/*physiology ; Pyramidal Cells/*physiology ; Rats ; Rats, Long-Evans ; *Space Perception ; *Spatial Behavior ; Spatial Processing ; }, abstract = {An animal's awareness of its location in space depends on the activity of place cells in the hippocampus. How the brain encodes the spatial position of others has not yet been identified. We investigated neuronal representations of other animals' locations in the dorsal CA1 region of the hippocampus with an observational T-maze task in which one rat was required to observe another rat's trajectory to successfully retrieve a reward. Information reflecting the spatial location of both the self and the other was jointly and discretely encoded by CA1 pyramidal cells in the observer rat. A subset of CA1 pyramidal cells exhibited spatial receptive fields that were identical for the self and the other. These findings demonstrate that hippocampal spatial representations include dimensions for both self and nonself.}, } @article {pmid29326272, year = {2018}, author = {Zhao, W and Caro, F and Robins, W and Mekalanos, JJ}, title = {Antagonism toward the intestinal microbiota and its effect on Vibrio cholerae virulence.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {210-213}, doi = {10.1126/science.aap8775}, pmid = {29326272}, issn = {1095-9203}, support = {R01 AI018045/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Antibiosis ; Cholera/immunology/metabolism/*microbiology ; Cytokines/genetics/metabolism ; Escherichia coli/growth & development ; Gastrointestinal Microbiome/*physiology ; Gene Expression Regulation ; Gene Expression Regulation, Bacterial ; Genetic Fitness ; Intestinal Mucosa/metabolism ; Intestines/immunology/microbiology ; Mice ; Mutation ; Symbiosis ; Transcription, Genetic ; Type VI Secretion Systems/genetics/*metabolism ; Vibrio cholerae/genetics/growth & development/*pathogenicity/*physiology ; Virulence ; }, abstract = {The bacterial type VI secretion system (T6SS) is a nanomachine that delivers toxic effector proteins into target cells, killing them. In mice, we found that the Vibrio cholerae T6SS attacks members of the host commensal microbiota in vivo, facilitating the pathogen's colonization of the gut. This microbial antagonistic interaction drives measurable changes in the pathogenicity of V. cholerae through enhanced intestinal colonization, expression of bacterial virulence genes, and activation of host innate immune genes. Because ablation of mouse commensals by this enteric pathogen correlated with more severe diarrheal symptoms, we conclude that antagonism toward the gut microbiota could improve the fitness of V. cholerae as a pathogen by elevating its transmission to new susceptible hosts.}, } @article {pmid29326271, year = {2018}, author = {Shen, K and Zhang, L and Chen, X and Liu, L and Zhang, D and Han, Y and Chen, J and Long, J and Luque, R and Li, Y and Chen, B}, title = {Ordered macro-microporous metal-organic framework single crystals.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {206-210}, doi = {10.1126/science.aao3403}, pmid = {29326271}, issn = {1095-9203}, abstract = {We constructed highly oriented and ordered macropores within metal-organic framework (MOF) single crystals, opening up the area of three-dimensional-ordered macro-microporous materials (that is, materials containing both macro- and micropores) in single-crystalline form. Our methodology relies on the strong shaping effects of a polystyrene nanosphere monolith template and a double-solvent-induced heterogeneous nucleation approach. This process synergistically enabled the in situ growth of MOFs within ordered voids, rendering a single crystal with oriented and ordered macro-microporous structure. The improved mass diffusion properties of such hierarchical frameworks, together with their robust single-crystalline nature, endow them with superior catalytic activity and recyclability for bulky-molecule reactions, as compared with conventional, polycrystalline hollow, and disordered macroporous ZIF-8.}, } @article {pmid29326270, year = {2018}, author = {McGuire, BA and Burkhardt, AM and Kalenskii, S and Shingledecker, CN and Remijan, AJ and Herbst, E and McCarthy, MC}, title = {Detection of the aromatic molecule benzonitrile (c-C6H5CN) in the interstellar medium.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {202-205}, doi = {10.1126/science.aao4890}, pmid = {29326270}, issn = {1095-9203}, abstract = {Polycyclic aromatic hydrocarbons and polycyclic aromatic nitrogen heterocycles are thought to be widespread throughout the universe, because these classes of molecules are probably responsible for the unidentified infrared bands, a set of emission features seen in numerous Galactic and extragalactic sources. Despite their expected ubiquity, astronomical identification of specific aromatic molecules has proven elusive. We present the discovery of benzonitrile (c-C6H5CN), one of the simplest nitrogen-bearing aromatic molecules, in the interstellar medium. We observed hyperfine-resolved transitions of benzonitrile in emission from the molecular cloud TMC-1. Simple aromatic molecules such as benzonitrile may be precursors for polycyclic aromatic hydrocarbon formation, providing a chemical link to the carriers of the unidentified infrared bands.}, } @article {pmid29326269, year = {2018}, author = {Dundas, CM and Bramson, AM and Ojha, L and Wray, JJ and Mellon, MT and Byrne, S and McEwen, AS and Putzig, NE and Viola, D and Sutton, S and Clark, E and Holt, JW}, title = {Exposed subsurface ice sheets in the Martian mid-latitudes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {199-201}, doi = {10.1126/science.aao1619}, pmid = {29326269}, issn = {1095-9203}, mesh = {*Extraterrestrial Environment ; *Ice Cover ; *Mars ; }, abstract = {Thick deposits cover broad regions of the Martian mid-latitudes with a smooth mantle; erosion in these regions creates scarps that expose the internal structure of the mantle. We investigated eight of these locations and found that they expose deposits of water ice that can be >100 meters thick, extending downward from depths as shallow as 1 to 2 meters below the surface. The scarps are actively retreating because of sublimation of the exposed water ice. The ice deposits likely originated as snowfall during Mars' high-obliquity periods and have now compacted into massive, fractured, and layered ice. We expect the vertical structure of Martian ice-rich deposits to preserve a record of ice deposition and past climate.}, } @article {pmid29326268, year = {2018}, author = {Cowell, AN and Istvan, ES and Lukens, AK and Gomez-Lorenzo, MG and Vanaerschot, M and Sakata-Kato, T and Flannery, EL and Magistrado, P and Owen, E and Abraham, M and LaMonte, G and Painter, HJ and Williams, RM and Franco, V and Linares, M and Arriaga, I and Bopp, S and Corey, VC and Gnädig, NF and Coburn-Flynn, O and Reimer, C and Gupta, P and Murithi, JM and Moura, PA and Fuchs, O and Sasaki, E and Kim, SW and Teng, CH and Wang, LT and Akidil, A and Adjalley, S and Willis, PA and Siegel, D and Tanaseichuk, O and Zhong, Y and Zhou, Y and Llinás, M and Ottilie, S and Gamo, FJ and Lee, MCS and Goldberg, DE and Fidock, DA and Wirth, DF and Winzeler, EA}, title = {Mapping the malaria parasite druggable genome by using in vitro evolution and chemogenomics.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {191-199}, pmid = {29326268}, issn = {1095-9203}, support = {R01 AI050234/AI/NIAID NIH HHS/United States ; T32 AI007036/AI/NIAID NIH HHS/United States ; R01 AI090141/AI/NIAID NIH HHS/United States ; R01 AI103058/AI/NIAID NIH HHS/United States ; R01 AI099105/AI/NIAID NIH HHS/United States ; R37 AI050234/AI/NIAID NIH HHS/United States ; T32 GM008666/GM/NIGMS NIH HHS/United States ; P50 GM085764/GM/NIGMS NIH HHS/United States ; T32 GM007198/GM/NIGMS NIH HHS/United States ; }, mesh = {Activation, Metabolic ; Alleles ; Antimalarials/*pharmacology ; DNA Copy Number Variations ; Directed Molecular Evolution ; Drug Resistance/*genetics ; Drug Resistance, Multiple/genetics ; Genes, Protozoan ; *Genome, Protozoan ; Metabolomics ; Mutation ; Plasmodium falciparum/*drug effects/*genetics/growth & development ; Selection, Genetic ; Transcription Factors/chemistry/genetics/metabolism ; }, abstract = {Chemogenetic characterization through in vitro evolution combined with whole-genome analysis can identify antimalarial drug targets and drug-resistance genes. We performed a genome analysis of 262 Plasmodium falciparum parasites resistant to 37 diverse compounds. We found 159 gene amplifications and 148 nonsynonymous changes in 83 genes associated with drug-resistance acquisition, where gene amplifications contributed to one-third of resistance acquisition events. Beyond confirming previously identified multidrug-resistance mechanisms, we discovered hitherto unrecognized drug target-inhibitor pairs, including thymidylate synthase and a benzoquinazolinone, farnesyltransferase and a pyrimidinedione, and a dipeptidylpeptidase and an arylurea. This exploration of the P. falciparum resistome and druggable genome will likely guide drug discovery and structural biology efforts, while also advancing our understanding of resistance mechanisms available to the malaria parasite.}, } @article {pmid29326267, year = {2018}, author = {Goremychkin, EA and Park, H and Osborn, R and Rosenkranz, S and Castellan, JP and Fanelli, VR and Christianson, AD and Stone, MB and Bauer, ED and McClellan, KJ and Byler, DD and Lawrence, JM}, title = {Coherent band excitations in CePd3: A comparison of neutron scattering and ab initio theory.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {186-191}, doi = {10.1126/science.aan0593}, pmid = {29326267}, issn = {1095-9203}, abstract = {In common with many strongly correlated electron systems, intermediate valence compounds are believed to display a crossover from a high-temperature regime of incoherently fluctuating local moments to a low-temperature regime of coherent hybridized bands. We show that inelastic neutron scattering measurements of the dynamic magnetic susceptibility of CePd3 provides a benchmark for ab initio calculations based on dynamical mean field theory. The magnetic response is strongly momentum dependent thanks to the formation of coherent f-electron bands at low temperature, with an amplitude that is strongly enhanced by local particle-hole interactions. The agreement between experiment and theory shows that we have a robust first-principles understanding of the temperature dependence of f-electron coherence.}, } @article {pmid29326266, year = {2018}, author = {Pace, L and Goudot, C and Zueva, E and Gueguen, P and Burgdorf, N and Waterfall, JJ and Quivy, JP and Almouzni, G and Amigorena, S}, title = {The epigenetic control of stemness in CD8+ T cell fate commitment.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {177-186}, doi = {10.1126/science.aah6499}, pmid = {29326266}, issn = {1095-9203}, mesh = {Animals ; CD8-Positive T-Lymphocytes/*immunology/*metabolism ; Cell Differentiation ; Cells, Cultured ; Chromatin/metabolism ; Epigenesis, Genetic ; Female ; *Gene Silencing ; Histone-Lysine N-Methyltransferase/genetics/*metabolism ; Histones/metabolism ; *Immunologic Memory ; Listeria monocytogenes/immunology ; Listeriosis/*immunology ; Male ; Methylation ; Methyltransferases/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Mice, Knockout ; RNA, Messenger/genetics/metabolism ; Repressor Proteins/genetics/*metabolism ; }, abstract = {After priming, naïve CD8+ T lymphocytes establish specific heritable transcription programs that define progression to long-lasting memory cells or to short-lived effector cells. Although lineage specification is critical for protection, it remains unclear how chromatin dynamics contributes to the control of gene expression programs. We explored the role of gene silencing by the histone methyltransferase Suv39h1. In murine CD8+ T cells activated after Listeria monocytogenes infection, Suv39h1-dependent trimethylation of histone H3 lysine 9 controls the expression of a set of stem cell-related memory genes. Single-cell RNA sequencing revealed a defect in silencing of stem/memory genes selectively in Suv39h1-defective T cell effectors. As a result, Suv39h1-defective CD8+ T cells show sustained survival and increased long-term memory reprogramming capacity. Thus, Suv39h1 plays a critical role in marking chromatin to silence stem/memory genes during CD8+ T effector terminal differentiation.}, } @article {pmid29326265, year = {2018}, author = {Nguyen, J and Newton, MS and Strong, M and Pačesa, M and Cao, B and Winter, KA and Dutton-Regester, K and Kingsley, LJ}, title = {The next generation's Frankenstein films.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {170-171}, doi = {10.1126/science.aas9105}, pmid = {29326265}, issn = {1095-9203}, mesh = {*Artificial Intelligence ; Gene Editing ; *Genetic Engineering ; Humans ; *Motion Pictures ; *Science in the Arts ; *Transplantation, Heterologous ; }, } @article {pmid29326264, year = {2018}, author = {Acuto, M}, title = {Global science for city policy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {165-166}, doi = {10.1126/science.aao2728}, pmid = {29326264}, issn = {1095-9203}, mesh = {*Cities ; Humans ; *Local Government ; *Public Policy ; *Science ; United Nations ; }, } @article {pmid29326263, year = {2018}, author = {Henning, AN and Klebanoff, CA and Restifo, NP}, title = {Silencing stemness in T cell differentiation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {163-164}, doi = {10.1126/science.aar5541}, pmid = {29326263}, issn = {1095-9203}, support = {Z01 BC010763-03/NULL/Intramural NIH HHS/United States ; }, mesh = {*Cell Differentiation ; Humans ; *Neoplastic Stem Cells ; }, } @article {pmid29326262, year = {2018}, author = {Georges, A}, title = {Coherent excitations revealed and calculated.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {162-163}, doi = {10.1126/science.aar2325}, pmid = {29326262}, issn = {1095-9203}, } @article {pmid29326261, year = {2018}, author = {Bae, C and Jara-Oseguera, A and Swartz, KJ}, title = {TRPM channels come into focus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {160-161}, doi = {10.1126/science.aar6205}, pmid = {29326261}, issn = {1095-9203}, mesh = {Humans ; *TRPM Cation Channels ; }, } @article {pmid29326260, year = {2018}, author = {Carlton, JM}, title = {Malaria parasite evolution in a test tube.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {159-160}, pmid = {29326260}, issn = {1095-9203}, support = {U19 AI089676/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Biological Evolution ; Host-Parasite Interactions ; Humans ; Malaria/parasitology ; *Parasites ; *Plasmodium ; }, } @article {pmid29326259, year = {2018}, author = {Wagner, CE}, title = {Improbable Big Birds.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {157-159}, doi = {10.1126/science.aar4796}, pmid = {29326259}, issn = {1095-9203}, } @article {pmid29326258, year = {2018}, author = {Joblin, C and Cernicharo, J}, title = {Detecting the building blocks of aromatics.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {156-157}, doi = {10.1126/science.aar4541}, pmid = {29326258}, issn = {1095-9203}, } @article {pmid29326257, year = {2018}, author = {Cohen, J}, title = {A glossary of Frankenwords.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {154}, doi = {10.1126/science.359.6372.154}, pmid = {29326257}, issn = {1095-9203}, mesh = {*Literature, Modern ; *Science in Literature ; *Terminology as Topic ; }, } @article {pmid29326256, year = {2018}, author = {Kupferschmidt, K}, title = {Taming the monsters of tomorrow.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {152-155}, doi = {10.1126/science.359.6372.152}, pmid = {29326256}, issn = {1095-9203}, mesh = {*Artificial Intelligence ; *Biological Science Disciplines ; Humans ; Philosophy ; Risk ; *Science ; *Technology ; }, } @article {pmid29326255, year = {2018}, author = {Shultz, D}, title = {Creating a modern monster.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {151}, doi = {10.1126/science.359.6372.151}, pmid = {29326255}, issn = {1095-9203}, mesh = {*Artificial Organs ; *Bionics ; *Cloning, Organism ; Humans ; *Organ Culture Techniques ; *Transplants ; }, } @article {pmid29326254, year = {2018}, author = {Cohen, J}, title = {How a horror story haunts science.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {148-150}, doi = {10.1126/science.359.6372.148}, pmid = {29326254}, issn = {1095-9203}, mesh = {*Biomedical Research/ethics ; Ethics, Research ; History, 19th Century ; *Literature, Modern/history ; *Publishing ; *Science in Literature/history ; Synthetic Biology ; }, } @article {pmid29326253, year = {2018}, author = {Kupferschmidt, K}, title = {The long shadow of Frankenstein.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {146-147}, doi = {10.1126/science.359.6372.146}, pmid = {29326253}, issn = {1095-9203}, mesh = {History, 19th Century ; Literature, Modern/*history ; Science in Literature/*history ; }, } @article {pmid29326252, year = {2018}, author = {Voosen, P}, title = {Cliffs of ice spied on Mars.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {145}, doi = {10.1126/science.359.6372.145}, pmid = {29326252}, issn = {1095-9203}, } @article {pmid29326251, year = {2018}, author = {Stone, R}, title = {Cuba's 100-year plan for climate change.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {144-145}, doi = {10.1126/science.359.6372.144}, pmid = {29326251}, issn = {1095-9203}, mesh = {*Climate Change ; Conservation of Natural Resources ; Cuba ; Ecosystem ; *Government Programs ; }, } @article {pmid29326250, year = {2018}, author = {Voosen, P}, title = {Earth scientists list top priorities for space missions.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {143}, doi = {10.1126/science.359.6372.143}, pmid = {29326250}, issn = {1095-9203}, } @article {pmid29326249, year = {2018}, author = {Roberts, L}, title = {In Pakistan, surveillance for polio reveals a paradox.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {142-143}, doi = {10.1126/science.359.6372.142}, pmid = {29326249}, issn = {1095-9203}, mesh = {Catchment Area (Health) ; Child ; Child, Preschool ; Disease Eradication ; *Epidemiological Monitoring ; Humans ; Immunization Programs ; Infant ; Pakistan/epidemiology ; Paralysis ; Poliomyelitis/*epidemiology/immunology/prevention & control ; Poliovirus/immunology/*isolation & purification/physiology ; Poliovirus Vaccines/administration & dosage ; Sewage/*virology ; }, } @article {pmid29326248, year = {2018}, author = {Cho, A}, title = {DOE pushes for useful quantum computing.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {141-142}, doi = {10.1126/science.359.6372.141}, pmid = {29326248}, issn = {1095-9203}, } @article {pmid29326246, year = {2018}, author = {van den Belt, H}, title = {Frankenstein lives on.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {137}, doi = {10.1126/science.aas9167}, pmid = {29326246}, issn = {1095-9203}, mesh = {Literature, Modern ; *Moral Obligations ; *Science ; *Science in Literature ; *Technology ; }, } @article {pmid29326245, year = {2018}, author = {Rana, MS and Kumar, P and Lee, CJ and Verardi, R and Rajashankar, KR and Banerjee, A}, title = {Fatty acyl recognition and transfer by an integral membrane S-acyltransferase.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {}, doi = {10.1126/science.aao6326}, pmid = {29326245}, issn = {1095-9203}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 OD012289/OD/NIH HHS/United States ; P30 GM124165/GM/NIGMS NIH HHS/United States ; Z99 HD999999/NULL/Intramural NIH HHS/United States ; ZIA HD008928/HD/NICHD NIH HHS/United States ; }, mesh = {Acyl Coenzyme A/*metabolism ; Acyltransferases/*chemistry/genetics/metabolism ; Animals ; Catalytic Domain ; Crystallization ; Crystallography, X-Ray ; Cysteine/chemistry ; Humans ; Lipoylation ; Models, Molecular ; Mutation ; Protein Domains ; Protein Structure, Secondary ; Substrate Specificity ; Zebrafish Proteins/*chemistry/genetics/metabolism ; }, abstract = {DHHC (Asp-His-His-Cys) palmitoyltransferases are eukaryotic integral membrane enzymes that catalyze protein palmitoylation, which is important in a range of physiological processes, including small guanosine triphosphatase (GTPase) signaling, cell adhesion, and neuronal receptor scaffolding. We present crystal structures of two DHHC palmitoyltransferases and a covalent intermediate mimic. The active site resides at the membrane-cytosol interface, which allows the enzyme to catalyze thioester-exchange chemistry by using fatty acyl-coenzyme A and explains why membrane-proximal cysteines are candidates for palmitoylation. The acyl chain binds in a cavity formed by the transmembrane domain. We propose a mechanism for acyl chain-length selectivity in DHHC enzymes on the basis of cavity mutants with preferences for shorter and longer acyl chains.}, } @article {pmid29326244, year = {2018}, author = {Dunbar, CE and High, KA and Joung, JK and Kohn, DB and Ozawa, K and Sadelain, M}, title = {Gene therapy comes of age.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {}, doi = {10.1126/science.aan4672}, pmid = {29326244}, issn = {1095-9203}, mesh = {Animals ; Gene Editing ; Gene Transfer Techniques ; Genetic Diseases, Inborn/therapy ; Genetic Engineering ; *Genetic Therapy/adverse effects ; Genetic Vectors ; Hematologic Diseases/therapy ; Humans ; Neoplasms/therapy ; Neuromuscular Diseases/therapy ; Translational Medical Research ; }, abstract = {After almost 30 years of promise tempered by setbacks, gene therapies are rapidly becoming a critical component of the therapeutic armamentarium for a variety of inherited and acquired human diseases. Gene therapies for inherited immune disorders, hemophilia, eye and neurodegenerative disorders, and lymphoid cancers recently progressed to approved drug status in the United States and Europe, or are anticipated to receive approval in the near future. In this Review, we discuss milestones in the development of gene therapies, focusing on direct in vivo administration of viral vectors and adoptive transfer of genetically engineered T cells or hematopoietic stem cells. We also discuss emerging genome editing technologies that should further advance the scope and efficacy of gene therapy approaches.}, } @article {pmid29326235, year = {2018}, author = {Moore, JC}, title = {Predicting tipping points in complex environmental systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {635-636}, pmid = {29326235}, issn = {1091-6490}, mesh = {*Conservation of Natural Resources ; *Ecosystem ; }, } @article {pmid29326234, year = {2018}, author = {Scheffer, M and van Nes, EH and Vergnon, R}, title = {Toward a unifying theory of biodiversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {639-641}, pmid = {29326234}, issn = {1091-6490}, mesh = {*Biodiversity ; *Ecology ; Models, Biological ; }, } @article {pmid29326233, year = {2018}, author = {Daly, M}, title = {Partitioning aggression.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {633-634}, pmid = {29326233}, issn = {1091-6490}, mesh = {*Aggression ; Animals ; *Behavior, Animal ; }, } @article {pmid29326232, year = {2018}, author = {Sluis-Cremer, N}, title = {Future of nonnucleoside reverse transcriptase inhibitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {637-638}, pmid = {29326232}, issn = {1091-6490}, support = {R01 AI081571/AI/NIAID NIH HHS/United States ; R01 GM068406/GM/NIGMS NIH HHS/United States ; }, mesh = {*Anti-HIV Agents ; Drug Resistance, Viral/drug effects ; HIV Infections ; HIV Reverse Transcriptase ; *Reverse Transcriptase Inhibitors ; }, } @article {pmid29326231, year = {2018}, author = {Suarez-Jimenez, B and Bisby, JA and Horner, AJ and King, JA and Pine, DS and Burgess, N}, title = {Linked networks for learning and expressing location-specific threat.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1032-E1040}, pmid = {29326231}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; T32 MH015144/MH/NIMH NIH HHS/United States ; 202805/Z/16/Z//Wellcome Trust/United Kingdom ; 203147/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Adult ; Amygdala/*physiology ; Anxiety/*physiopathology ; Brain Mapping/*methods ; *Fear ; Female ; Healthy Volunteers ; Hippocampus/*physiology ; Humans ; *Learning ; Magnetic Resonance Imaging ; Male ; Prefrontal Cortex/*physiology ; Skin/metabolism ; Skin Physiological Phenomena ; Young Adult ; }, abstract = {Learning locations of danger within our environment is a vital adaptive ability whose neural bases are only partially understood. We examined fMRI brain activity while participants navigated a virtual environment in which flowers appeared and were "picked." Picking flowers in the danger zone (one-half of the environment) predicted an electric shock to the wrist (or "bee sting"); flowers in the safe zone never predicted shock; and household objects served as controls for neutral spatial memory. Participants demonstrated learning with shock expectancy ratings and skin conductance increases for flowers in the danger zone. Patterns of brain activity shifted between overlapping networks during different task stages. Learning about environmental threats, during flower approach in either zone, engaged the anterior hippocampus, amygdala, and ventromedial prefrontal cortex (vmPFC), with vmPFC-hippocampal functional connectivity increasing with experience. Threat appraisal, during approach in the danger zone, engaged the insula and dorsal anterior cingulate (dACC), with insula-hippocampal functional connectivity. During imminent threat, after picking a flower, this pattern was supplemented by activity in periaqueductal gray (PAG), insula-dACC coupling, and posterior hippocampal activity that increased with experience. We interpret these patterns in terms of multiple representations of spatial context (anterior hippocampus); specific locations (posterior hippocampus); stimuli (amygdala); value (vmPFC); threat, both visceral (insula) and cognitive (dACC); and defensive behaviors (PAG), interacting in different combinations to perform the functions required at each task stage. Our findings illuminate how we learn about location-specific threats and suggest how they might break down into overgeneralization or hypervigilance in anxiety disorders.}, } @article {pmid29326118, year = {2018}, author = {Zhou, H and Peng, C and Yoon, Y and Hsu, CW and Nelson, KA and Fu, L and Joannopoulos, JD and Soljačić, M and Zhen, B}, title = {Observation of bulk Fermi arc and polarization half charge from paired exceptional points.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1009-1012}, doi = {10.1126/science.aap9859}, pmid = {29326118}, issn = {1095-9203}, abstract = {The ideas of topology have found tremendous success in closed physical systems, but even richer properties exist in the more general open or dissipative framework. We theoretically propose and experimentally demonstrate a bulk Fermi arc that develops from non-Hermitian radiative losses in an open system of photonic crystal slabs. Moreover, we discover half-integer topological charges in the polarization of far-field radiation around the bulk Fermi arc. Both phenomena are shown to be direct consequences of the non-Hermitian topological properties of exceptional points, where resonances coincide in their frequencies and linewidths. Our work connects the fields of topological photonics, non-Hermitian physics, and singular optics, providing a framework to explore more complex non-Hermitian topological systems.}, } @article {pmid29326117, year = {2018}, author = {Yang, B and Guo, Q and Tremain, B and Liu, R and Barr, LE and Yan, Q and Gao, W and Liu, H and Xiang, Y and Chen, J and Fang, C and Hibbins, A and Lu, L and Zhang, S}, title = {Ideal Weyl points and helicoid surface states in artificial photonic crystal structures.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6379}, pages = {1013-1016}, doi = {10.1126/science.aaq1221}, pmid = {29326117}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {Weyl points are the crossings of linearly dispersing energy bands of three-dimensional crystals, providing the opportunity to explore a variety of intriguing phenomena such as topologically protected surface states and chiral anomalies. However, the lack of an ideal Weyl system in which the Weyl points all exist at the same energy and are separated from any other bands poses a serious limitation to the further development of Weyl physics and potential applications. By experimentally characterizing a microwave photonic crystal of saddle-shaped metallic coils, we observed ideal Weyl points that are related to each other through symmetry operations. Topological surface states exhibiting helicoidal structure have also been demonstrated. Our system provides a photonic platform for exploring ideal Weyl systems and developing possible topological devices.}, } @article {pmid29325921, year = {2018}, author = {Barnes, AD and Jochum, M and Lefcheck, JS and Eisenhauer, N and Scherber, C and O'Connor, MI and de Ruiter, P and Brose, U}, title = {Energy Flux: The Link between Multitrophic Biodiversity and Ecosystem Functioning.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {186-197}, pmid = {29325921}, issn = {1872-8383}, support = {677232//European Research Council/International ; }, mesh = {*Biodiversity ; Ecosystem ; *Food Chain ; Models, Biological ; }, abstract = {Relating biodiversity to ecosystem functioning in natural communities has become a paramount challenge as links between trophic complexity and multiple ecosystem functions become increasingly apparent. Yet, there is still no generalised approach to address such complexity in biodiversity-ecosystem functioning (BEF) studies. Energy flux dynamics in ecological networks provide the theoretical underpinning of multitrophic BEF relationships. Accordingly, we propose the quantification of energy fluxes in food webs as a powerful, universal tool for understanding ecosystem functioning in multitrophic systems spanning different ecological scales. Although the concept of energy flux in food webs is not novel, its application to BEF research remains virtually untapped, providing a framework to foster new discoveries into the determinants of ecosystem functioning in complex systems.}, } @article {pmid29325587, year = {2018}, author = {Sah, R and Khadka, S and Hamal, R and Poudyal, S}, title = {Human echinostomiasis: a case report.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {17}, pmid = {29325587}, issn = {1756-0500}, mesh = {Echinostomiasis/*diagnosis ; Humans ; Male ; Middle Aged ; Nepal ; }, abstract = {BACKGROUND: Echinostomiasis is a food-borne infection caused by an intestinal trematodes belonging to the family Echinostomatidae. They infect the gastrointestinal tract of humans. Patients are usually asymptomatic. However, with heavy infections, the worms can produce catarrhal inflammation with mild ulceration and the patient may experience abdominal pain, anorexia, nausea, vomiting, diarrhea and weight loss. Infection are associated with common sociocultural practices of eating raw or insufficiently cooked mollusks and fish.

CASE PRESENTATION: We report a first case of echinostomiasis from Nepal in a 62 years old, hindu male who presented to Tribhuvan University Teaching Hospital, Kathmandu with a complaint of abdominal pain and distension with vomiting on and off for 3-4 months. He had history of consumption of insufficiently cooked fish and snail with alcohol. During endoscopy, an adult flat worm was seen with mild portal hypertensive gastropathy (McCormack's classification) and erosive duodenopathy. The adult worm was identified as Echinostoma species based on its morphology and characteristic ova found on stool routine microscopic examination of the patient. Patient was treated with praziquantel 40 mg/kg (single dose) which is the drug of choice for Echinostoma species infection by which he got improved and on follow up stool examination after 2 weeks revealed no ova of Echinostoma species.

CONCLUSIONS: The patients having history of consumption of insufficiently cooked snail and fish with suggestive clinical features of echinostomiasis should be suspected by physicians and ova of Echinostoma species should be searched by trained microscopists. An epidemiological survey is required to know the exact burden of Echinostoma species infection in the place where people have habit of eating insufficiently cooked fish and snails, as it can be endemic in that community or geographical area.}, } @article {pmid29325581, year = {2018}, author = {Ederveen, THA and Ferwerda, G and Ahout, IM and Vissers, M and de Groot, R and Boekhorst, J and Timmerman, HM and Huynen, MA and van Hijum, SAFT and de Jonge, MI}, title = {Haemophilus is overrepresented in the nasopharynx of infants hospitalized with RSV infection and associated with increased viral load and enhanced mucosal CXCL8 responses.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {10}, pmid = {29325581}, issn = {2049-2618}, support = {FES0908//VIRGO consortium (Netherlands Genomics Initiative and the Dutch Government)/International ; 634415//PoC-ID consortium (EU Horizon2020)/International ; }, mesh = {DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Female ; Haemophilus/*classification/genetics/isolation & purification ; Hospitalization ; Humans ; Infant ; Infant, Newborn ; Interleukin-8/*metabolism ; Male ; Nasopharynx/*microbiology ; RNA, Ribosomal, 16S/genetics ; Respiratory Syncytial Virus Infections/immunology/*virology ; Respiratory Syncytial Viruses/*physiology ; Sequence Analysis, DNA/methods ; Up-Regulation ; Viral Load ; }, abstract = {BACKGROUND: While almost all infants are infected with respiratory syncytial virus (RSV) before the age of 2 years, only a small percentage develops severe disease. Previous studies suggest that the nasopharyngeal microbiome affects disease development. We therefore studied the effect of the nasopharyngeal microbiome on viral load and mucosal cytokine responses, two important factors influencing the pathophysiology of RSV disease. To determine the relation between (i) the microbiome of the upper respiratory tract, (ii) viral load, and (iii) host mucosal inflammation during an RSV infection, nasopharyngeal microbiota profiles of RSV infected infants (< 6 months) with different levels of disease severity and age-matched healthy controls were determined by 16S rRNA marker gene sequencing. The viral load was measured using qPCR. Nasopharyngeal CCL5, CXCL10, MMP9, IL6, and CXCL8 levels were determined with ELISA.

RESULTS: Viral load in nasopharyngeal aspirates of patients associates significantly to total nasopharyngeal microbiota composition. Healthy infants (n = 21) and RSV patients (n = 54) display very distinct microbial patterns, primarily characterized by a loss in commensals like Veillonella and overrepresentation of opportunistic organisms like Haemophilus and Achromobacter in RSV-infected individuals. Furthermore, nasopharyngeal microbiota profiles are significantly different based on CXCL8 levels. CXCL8 is a chemokine that was previously found to be indicative for disease severity and for which we find Haemophilus abundance as the strongest predictor for CXCL8 levels.

CONCLUSIONS: The nasopharyngeal microbiota in young infants with RSV infection is marked by an overrepresentation of the genus Haemophilus. We present that this bacterium is associated with viral load and mucosal CXCL8 responses, both which are involved in RSV disease pathogenesis.}, } @article {pmid29325576, year = {2018}, author = {Strouhal, M and Oppelt, J and Mikalová, L and Arora, N and Nieselt, K and González-Candelas, F and Šmajs, D}, title = {Reanalysis of Chinese Treponema pallidum samples: all Chinese samples cluster with SS14-like group of syphilis-causing treponemes.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {16}, pmid = {29325576}, issn = {1756-0500}, support = {GA17-25455S//Grantová Agentura České Republiky/ ; GJ17-25589Y//Grantová Agentura České Republiky/ ; 17-31333A//Czech Health Research Council/ ; }, mesh = {China ; Genome, Bacterial/*genetics ; Humans ; *Phylogeny ; Polymorphism, Single Nucleotide/*genetics ; *Sequence Analysis, DNA ; Treponema pallidum/*genetics ; }, abstract = {OBJECTIVE: Treponema pallidum subsp. pallidum (TPA) is the causative agent of syphilis. Genetic analyses of TPA reference strains and human clinical isolates have revealed two genetically distinct groups of syphilis-causing treponemes, called Nichols-like and SS14-like groups. So far, no genetic intermediates, i.e. strains containing a mixed pattern of Nichols-like and SS14-like genomic sequences, have been identified. Recently, Sun et al. (Oncotarget 2016. https://doi.org/10.18632/oncotarget.10154) described a new "phylogenetic group" (called Lineage 2) among Chinese TPA strains. This lineage exhibited a "mosaic genomic structure" of Nichols-like and SS14-like lineages.

RESULTS: We reanalyzed the primary sequencing data (Project Number PRJNA305961) from the Sun et al. publication with respect to the molecular basis of Lineage 2. While Sun et al. based the analysis on several selected genomic single nucleotide variants (SNVs) and a subset of highly variable but phylogenetically poorly informative genes, which may confound the phylogenetic analysis, our reanalysis primarily focused on a complete set of whole genomic SNVs. Based on our reanalysis, only two separate TPA clusters were identified: one consisted of Nichols-like TPA strains, the other was formed by the SS14-like TPA strains, including all Chinese strains.}, } @article {pmid29325570, year = {2018}, author = {Eccles, D and Chandler, J and Camberis, M and Henrissat, B and Koren, S and Le Gros, G and Ewbank, JJ}, title = {De novo assembly of the complex genome of Nippostrongylus brasiliensis using MinION long reads.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {6}, pmid = {29325570}, issn = {1741-7007}, abstract = {BACKGROUND: Eukaryotic genome assembly remains a challenge in part due to the prevalence of complex DNA repeats. This is a particularly acute problem for holocentric nematodes because of the large number of satellite DNA sequences found throughout their genomes. These have been recalcitrant to most genome sequencing methods. At the same time, many nematodes are parasites and some represent a serious threat to human health. There is a pressing need for better molecular characterization of animal and plant parasitic nematodes. The advent of long-read DNA sequencing methods offers the promise of resolving complex genomes.

RESULTS: Using Nippostrongylus brasiliensis as a test case, applying improved base-calling algorithms and assembly methods, we demonstrate the feasibility of de novo genome assembly matching current community standards using only MinION long reads. In doing so, we uncovered an unexpected diversity of very long and complex DNA sequences repeated throughout the N. brasiliensis genome, including massive tandem repeats of tRNA genes.

CONCLUSION: Base-calling and assembly methods have improved sufficiently that de novo genome assembly of large complex genomes is possible using only long reads. The method has the added advantage of preserving haplotypic variants and so has the potential to be used in population analyses.}, } @article {pmid29325568, year = {2018}, author = {Sekine, S and Youle, RJ}, title = {PINK1 import regulation; a fine system to convey mitochondrial stress to the cytosol.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {2}, pmid = {29325568}, issn = {1741-7007}, abstract = {Insights from inherited forms of parkinsonism suggest that insufficient mitophagy may be one etiology of the disease. PINK1/Parkin-dependent mitophagy, which helps maintain a healthy mitochondrial network, is initiated by activation of the PINK1 kinase specifically on damaged mitochondria. Recent investigation of this process reveals that import of PINK1 into mitochondria is regulated and yields a stress-sensing mechanism. In this review, we focus on the mechanisms of mitochondrial stress-dependent PINK1 activation that is exerted by regulated import of PINK1 into different mitochondrial compartments and how this offers strategies to pharmacologically activate the PINK1/Parkin pathway.}, } @article {pmid29325559, year = {2018}, author = {Plissonneau, C and Hartmann, FE and Croll, D}, title = {Pangenome analyses of the wheat pathogen Zymoseptoria tritici reveal the structural basis of a highly plastic eukaryotic genome.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {5}, pmid = {29325559}, issn = {1741-7007}, abstract = {BACKGROUND: Structural variation contributes substantially to polymorphism within species. Chromosomal rearrangements that impact genes can lead to functional variation among individuals and influence the expression of phenotypic traits. Genomes of fungal pathogens show substantial chromosomal polymorphism that can drive virulence evolution on host plants. Assessing the adaptive significance of structural variation is challenging, because most studies rely on inferences based on a single reference genome sequence.

RESULTS: We constructed and analyzed the pangenome of Zymoseptoria tritici, a major pathogen of wheat that evolved host specialization by chromosomal rearrangements and gene deletions. We used single-molecule real-time sequencing and high-density genetic maps to assemble multiple genomes. We annotated the gene space based on transcriptomics data that covered the infection life cycle of each strain. Based on a total of five telomere-to-telomere genomes, we constructed a pangenome for the species and identified a core set of 9149 genes. However, an additional 6600 genes were exclusive to a subset of the isolates. The substantial accessory genome encoded on average fewer expressed genes but a larger fraction of the candidate effector genes that may interact with the host during infection. We expanded our analyses of the pangenome to a worldwide collection of 123 isolates of the same species. We confirmed that accessory genes were indeed more likely to show deletion polymorphisms and loss-of-function mutations compared to core genes.

CONCLUSIONS: The pangenome construction of a highly polymorphic eukaryotic pathogen showed that a single reference genome significantly underestimates the gene space of a species. The substantial accessory genome provides a cradle for adaptive evolution.}, } @article {pmid29325558, year = {2018}, author = {Li, YF and Altman, RB}, title = {Systematic target function annotation of human transcription factors.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {4}, pmid = {29325558}, issn = {1741-7007}, support = {R24 GM061374/GM/NIGMS NIH HHS/United States ; GM61374/NH/NIH HHS/United States ; HL117798/NH/NIH HHS/United States ; }, abstract = {BACKGROUND: Transcription factors (TFs), the key players in transcriptional regulation, have attracted great experimental attention, yet the functions of most human TFs remain poorly understood. Recent capabilities in genome-wide protein binding profiling have stimulated systematic studies of the hierarchical organization of human gene regulatory network and DNA-binding specificity of TFs, shedding light on combinatorial gene regulation. We show here that these data also enable a systematic annotation of the biological functions and functional diversity of TFs.

RESULT: We compiled a human gene regulatory network for 384 TFs covering the 146,096 TF-target gene (TF-TG) relationships, extracted from over 850 ChIP-seq experiments as well as the literature. By integrating this network of TF-TF and TF-TG relationships with 3715 functional concepts from six sources of gene function annotations, we obtained over 9000 confident functional annotations for 279 TFs. We observe extensive connectivity between TFs and Mendelian diseases, GWAS phenotypes, and pharmacogenetic pathways. Further, we show that TFs link apparently unrelated functions, even when the two functions do not share common genes. Finally, we analyze the pleiotropic functions of TFs and suggest that the increased number of upstream regulators contributes to the functional pleiotropy of TFs.

CONCLUSION: Our computational approach is complementary to focused experimental studies on TF functions, and the resulting knowledge can guide experimental design for the discovery of unknown roles of TFs in human disease and drug response.}, } @article {pmid29325545, year = {2018}, author = {Lerner, TR and Queval, CJ and Fearns, A and Repnik, U and Griffiths, G and Gutierrez, MG}, title = {Phthiocerol dimycocerosates promote access to the cytosol and intracellular burden of Mycobacterium tuberculosis in lymphatic endothelial cells.}, journal = {BMC biology}, volume = {16}, number = {1}, pages = {1}, pmid = {29325545}, issn = {1741-7007}, support = {MC_UP_1202/11//Medical Research Council/United Kingdom ; FC001092//Medical Research Council/United Kingdom ; FC001092//Wellcome Trust/United Kingdom ; FC001092//Cancer Research UK/United Kingdom ; }, abstract = {BACKGROUND: Phthiocerol dimycocerosates (PDIM), glycolipids found on the outer surface of virulent members of the Mycobacterium tuberculosis (Mtb) complex, are a major contributing factor to the pathogenesis of Mtb. Myelocytic cells, such as macrophages and dendritic cells, are the primary hosts for Mtb after infection and previous studies have shown multiple roles for PDIM in supporting Mtb in these cells. However, Mtb can infect other cell types. We previously showed that Mtb efficiently replicates in human lymphatic endothelial cells (hLECs) and that the hLEC cytosol acts as a reservoir for Mtb in humans. Here, we examined the role of PDIM in Mtb translocation to the cytosol in hLECs.

RESULTS: Analysis of a Mtb mutant unable to produce PDIM showed less co-localisation of bacteria with the membrane damage marker Galectin-8 (Gal8), indicating that PDIM strongly contribute to phagosomal membrane damage. Lack of this Mtb lipid also leads to a reduction in the proportion of Mtb co-localising with markers of macroautophagic removal of intracellular bacteria (xenophagy) such as ubiquitin, p62 and NDP52. hLEC imaging with transmission electron microscopy shows that Mtb mutants lacking PDIM are much less frequently localised in the cytosol, leading to a lower intracellular burden.

CONCLUSIONS: PDIM is needed for the disruption of the phagosome membrane in hLEC, helping Mtb avoid the hydrolytic phagolysosomal milieu. It facilitates the translocation of Mtb into the cytosol, and the decreased intracellular burden of Mtb lacking PDIM indicates that the cytosol is the preferred replicative niche for Mtb in these cells. We hypothesise that pharmacological targeting of PDIM synthesis in Mtb would reduce the formation of a lymphatic reservoir of Mtb in humans.}, } @article {pmid29325522, year = {2018}, author = {Zhang, P and Dimont, E and Ha, T and Swanson, DJ and Itoh, M and Kawaji, H and Lassmann, T and Daub, CO and Arner, E and , and Carninci, P and Hayashizaki, Y and Forrest, ARR and Hide, W and Goldowitz, D}, title = {Correction to: Relatively frequent switching of transcription start sites during cerebellar development.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {39}, pmid = {29325522}, issn = {1471-2164}, abstract = {CORRECTION: The authors of the original article [1] would like to recognize the critical contribution of core members of the FANTOM5 Consortium, who played the critical role of HeliScopeCAGE sequencing experiments, quality control of tag reads and processing of the raw sequencing data.}, } @article {pmid29325130, year = {2018}, author = {Ren, Y and Wang, C and Chen, Z and Allan, E and van der Mei, HC and Busscher, HJ}, title = {Emergent heterogeneous microenvironments in biofilms: substratum surface heterogeneity and bacterial adhesion force-sensing.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {259-272}, doi = {10.1093/femsre/fuy001}, pmid = {29325130}, issn = {1574-6976}, mesh = {Bacterial Adhesion/*physiology ; *Biofilms ; *Environment ; Quorum Sensing ; }, abstract = {Phenotypically heterogeneous microenvironments emerge as biofilms mature across different environments. Phenotypic heterogeneity in biofilm sub-populations not obeying quorum sensing-dictated, collective group behavior may be considered as a strategy allowing non-conformists to survive hostile conditions. Heterogeneous phenotype development has been amply studied with respect to gene expression and genotypic changes, but 'biofilm genes' responsible for preprogrammed development of heterogeneous microenvironments in biofilms have never been discovered. Moreover, the question of what triggers the development of phenotypically heterogeneous microenvironments has never been addressed. The definition of biofilms as 'surface-adhering and surface-adapted' microbial communities contains the word 'surface' twice. This leads us to hypothesize that phenotypically heterogeneous microenvironments in biofilms develop as an adaptive response of initial colonizers to their adhering state, governed by the forces through which they adhere to a substratum surface. No surface is entirely homogeneous, while adhering bacteria can substantially contribute to stochastically occurring surface heterogeneity. Accordingly, bacterial adhesion forces sensed by initial colonizers differ across a substratum surface, leading to differential mechanical deformation of the cell wall and membrane, where many environmental sensors are located. Bacteria directly adhering to heterogeneous substratum domains therewith formulate their own local responses to their adhering state and command non-conformist behavior, leading to phenotypically heterogeneous microenvironments in biofilms.}, } @article {pmid29325123, year = {2018}, author = {Tomasch, J and Wang, H and Hall, ATK and Patzelt, D and Preusse, M and Petersen, J and Brinkmann, H and Bunk, B and Bhuju, S and Jarek, M and Geffers, R and Lang, AS and Wagner-Döbler, I}, title = {Packaging of Dinoroseobacter shibae DNA into Gene Transfer Agent Particles Is Not Random.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {359-369}, pmid = {29325123}, issn = {1759-6653}, mesh = {Bacterial Proteins/genetics ; Base Composition ; DNA, Bacterial/*genetics ; *Gene Transfer, Horizontal ; Multigene Family ; Oceans and Seas ; Rhodobacteraceae/*genetics ; }, abstract = {Gene transfer agents (GTAs) are phage-like particles which contain a fragment of genomic DNA of the bacterial or archaeal producer and deliver this to a recipient cell. GTA gene clusters are present in the genomes of almost all marine Rhodobacteraceae (Roseobacters) and might be important contributors to horizontal gene transfer in the world's oceans. For all organisms studied so far, no obvious evidence of sequence specificity or other nonrandom process responsible for packaging genomic DNA into GTAs has been found. Here, we show that knock-out of an autoinducer synthase gene of Dinoroseobacter shibae resulted in overproduction and release of functional GTA particles (DsGTA). Next-generation sequencing of the 4.2-kb DNA fragments isolated from DsGTAs revealed that packaging was not random. DNA from low-GC conjugative plasmids but not from high-GC chromids was excluded from packaging. Seven chromosomal regions were strongly overrepresented in DNA isolated from DsGTA. These packaging peaks lacked identifiable conserved sequence motifs that might represent recognition sites for the GTA terminase complex. Low-GC regions of the chromosome, including the origin and terminus of replication, were underrepresented in DNA isolated from DsGTAs. DNA methylation reduced packaging frequency while the level of gene expression had no influence. Chromosomal regions found to be over- and underrepresented in DsGTA-DNA were regularly spaced. We propose that a "headful" type of packaging is initiated at the sites of coverage peaks and, after linearization of the chromosomal DNA, proceeds in both directions from the initiation site. GC-content, DNA-modifications, and chromatin structure might influence at which sides GTA packaging can be initiated.}, } @article {pmid29325122, year = {2018}, author = {Kojima, KK}, title = {LINEs Contribute to the Origins of Middle Bodies of SINEs besides 3' Tails.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {370-379}, pmid = {29325122}, issn = {1759-6653}, mesh = {Animals ; Base Sequence ; *Evolution, Molecular ; *Long Interspersed Nucleotide Elements ; Sequence Alignment ; *Short Interspersed Nucleotide Elements ; }, abstract = {Short interspersed elements (SINEs), which are nonautonomous transposable elements, require the transposition machinery of long interspersed elements (LINEs) to mobilize. SINEs are composed of two or more independently originating parts. The 5' region is called the "head" and is derived mainly from small RNAs, and the 3' region ("tail") originates from the 3' region of LINEs and is responsible for being recognized by counterpart LINE proteins. The origin of the middle "body" of SINEs is enigmatic, although significant sequence similarities among SINEs from very diverse species have been observed. Here, a systematic analysis of the similarities among SINEs and LINEs deposited on Repbase, a comprehensive database of eukaryotic repeat sequences was performed. Three primary findings are described: 1) The 5' regions of only two clades of LINEs, RTE and Vingi, were revealed to have contributed to the middle parts of SINEs; 2) The linkage of the 5' and 3' parts of LINEs can be lost due to occasional tail exchange of SINEs; and 3) The previously proposed Ceph-domain was revealed to be a fusion of a CORE-domain and a 5' part of RTE clade of LINE. Based on these findings, a hypothesis that the 5' parts of bipartite nonautonomous LINEs, which possess only the 5' and 3' regions of the original LINEs, can contribute to the undefined middle part of SINEs is proposed.}, } @article {pmid29325102, year = {2018}, author = {Makino, T and Rubin, CJ and Carneiro, M and Axelsson, E and Andersson, L and Webster, MT}, title = {Elevated Proportions of Deleterious Genetic Variation in Domestic Animals and Plants.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {276-290}, pmid = {29325102}, issn = {1759-6653}, mesh = {Animals ; Animals, Domestic/*genetics ; Bombyx/genetics ; Chickens/genetics ; Crops, Agricultural/*genetics ; Dogs/genetics ; *Domestication ; Gene Frequency ; *Genetic Variation ; Oryza/genetics ; Polymorphism, Single Nucleotide ; Rabbits/genetics ; Selection, Genetic ; Soybeans/genetics ; Swine/genetics ; }, abstract = {A fraction of genetic variants segregating in any population are deleterious, which negatively impacts individual fitness. The domestication of animals and plants is associated with population bottlenecks and artificial selection, which are predicted to increase the proportion of deleterious variants. However, the extent to which this is a general feature of domestic species is unclear. Here, we examine the effects of domestication on the prevalence of deleterious variation using pooled whole-genome resequencing data from five domestic animal species (dog, pig, rabbit, chicken, and silkworm) and two domestic plant species (rice and soybean) compared with their wild ancestors. We find significantly reduced genetic variation and increased proportion of nonsynonymous amino acid changes in all but one of the domestic species. These differences are observable across a range of allele frequencies, both common and rare. We find proportionally more single nucleotide polymorphisms in highly conserved elements in domestic species and a tendency for domestic species to harbor a higher proportion of changes classified as damaging. Our findings most likely reflect an increased incidence of deleterious variants in domestic species, which is most likely attributable to population bottlenecks that lead to a reduction in the efficacy of selection. An exception to this pattern is displayed by European domestic pigs, which do not show traces of a strong population bottleneck and probably continued to exchange genes with wild boar populations after domestication. The results presented here indicate that an elevated proportion of deleterious variants is a common, but not ubiquitous, feature of domestic species.}, } @article {pmid29325042, year = {2018}, author = {Ndeh, D and Gilbert, HJ}, title = {Biochemistry of complex glycan depolymerisation by the human gut microbiota.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {2}, pages = {146-164}, doi = {10.1093/femsre/fuy002}, pmid = {29325042}, issn = {1574-6976}, mesh = {Bacteria/enzymology/metabolism ; Diet ; Gastrointestinal Microbiome/*physiology ; Humans ; Polysaccharides/*metabolism ; }, abstract = {The human gut microbiota (HGM) makes an important contribution to health and disease. It is a complex microbial community of trillions of microbes with a majority of its members represented within two phyla, the Bacteroidetes and Firmicutes, although it also contains species of Actinobacteria and Proteobacteria. Reflecting its importance, the HGM is sometimes referred to as an 'organ' as it performs functions analogous to systemic tissues within the human host. The major nutrients available to the HGM are host and dietary complex carbohydrates. To utilise these nutrient sources, the HGM has developed elaborate, variable and sophisticated systems for the sensing, capture and utilisation of these glycans. Understanding nutrient acquisition by the HGM can thus provide mechanistic insights into the dynamics of this ecosystem, and how it impacts human health. Dietary nutrient sources include a wide variety of simple and complex plant and animal-derived glycans most of which are not degraded by enzymes in the digestive tract of the host. Here we review how various adaptive mechanisms that operate across the major phyla of the HGM contribute to glycan utilisation, focusing on the most complex carbohydrates presented to this ecosystem.}, } @article {pmid29325030, year = {2018}, author = {Patiño Galindo, JÁ and González Candelas, F and Pybus, OG}, title = {The effect of RNA substitution models on viroid and RNA virus phylogenies.}, journal = {Genome biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29325030}, issn = {1759-6653}, abstract = {Many viroids and RNA viruses have genomes that exhibit secondary structure, with paired nucleotides forming stems and loops. Such structures violate a key assumption of most methods of phylogenetic reconstruction, that sequence change is independent among sites. However, phylogenetic analyses of these transmissible agents rarely use evolutionary models that account for RNA secondary structure. Here we assess the effect of using RNA-specific nucleotide substitution models on the phylogenetic inference of viroids and RNA viruses. We obtained data sets comprising full-genome nucleotide sequences from 6 viroid and 10 single-stranded RNA virus species. For each alignment, we inferred consensus RNA secondary structures, then evaluated different DNA and RNA substitution models. We used model selection to choose the best-fitting model and evaluate estimated Bayesian phylogenies. Further, for each data set we generated and compared Robinson-Foulds (RF) statistics in order to test whether the distributions of trees generated under alternative models are notably different to each other. In all alignments, the best-fitting model was one that considers RNA secondary structure: RNA models that allow a non-zero rate of double substitution (RNA16A, RNA16C) fitted best for both viral and viroid data sets. In 14 of 16 data sets, the use of an RNA-specific model led to significantly longer tree lengths, but only in 3 cases did it have a significant effect on RFs. In conclusion, using RNA model when undertaking phylogenetic inference of viroids and RNA viruses can provide a better model fit than standard approaches and model choice can significantly affect branch length estimates.}, } @article {pmid29325027, year = {2018}, author = {Vonaesch, P and Anderson, M and Sansonetti, PJ}, title = {Pathogens, microbiome and the host: emergence of the ecological Koch's postulates.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {3}, pages = {273-292}, doi = {10.1093/femsre/fuy003}, pmid = {29325027}, issn = {1574-6976}, mesh = {Ecology ; *Ecosystem ; Gastrointestinal Microbiome/*physiology ; Host-Pathogen Interactions/*physiology ; Humans ; }, abstract = {Even though tremendous progress has been made in the last decades to elucidate the mechanisms of intestinal homeostasis, dysbiosis and disease, we are only at the beginning of understanding the complexity of the gut ecosystem and the underlying interaction networks. We are also only starting to unravel the mechanisms that pathogens have evolved to overcome the barriers imposed by the microbiota and host to exploit the system to their own benefit. Recent work in these domains clearly indicates that the 'traditional Koch's postulates', which state that a given pathogen leads to a distinct disease, are not valid for all 'infectious' diseases, but that a more complete and complex interpretation of Koch's postulates is needed in order to understand and explain them. This review summarises the current understanding of what defines a healthy gut ecosystem and highlights recent progress in uncovering the interplay between the host, its microbiota and invading intestinal pathogens. Based on these recent findings, we propose a new interpretation of Koch's postulates that we term 'ecological Koch's postulates'.}, } @article {pmid29325015, year = {2018}, author = {Waring, B and Hawkes, CV}, title = {Ecological mechanisms underlying soil bacterial responses to rainfall along a steep natural precipitation gradient.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fiy001}, pmid = {29325015}, issn = {1574-6941}, abstract = {Changes in the structure and function of soil microbial communities can drive substantial ecosystem feedbacks to altered precipitation. However, the ecological mechanisms underlying community responses to environmental change are not well understood. We used an 18-month soil reciprocal transplant experiment along a steep precipitation gradient to quantify how changes in rainfall affected bacterial community structure. We also conducted an enhanced dispersal treatment to ask whether higher immigration rates of taxa from the surrounding environment would accelerate community responses to climate change. Finally, we addressed how the composition of soil bacteria communities was related to the functional response of soil respiration to moisture in these treatments. Bacterial community structure (OTU abundance) and function (respiration rates) changed little in response to manipulation of either rainfall environment or dispersal rates. Although most bacteria were ecological generalists, a subset of specialist taxa, over 40% of which were Actinobacteria, tended to be more abundant in the rainfall environment that matched their original conditions. Bacteria community composition was an important predictor of the respiration response to moisture. Thus, the high compositional resistance of microbial communities dictated respiration responses to altered rainfall in this system.}, } @article {pmid29325007, year = {2018}, author = {Rosas, T and García-Ferris, C and Domínguez-Santos, R and Llop, P and Latorre, A and Moya, A}, title = {Rifampicin treatment of Blattella germanica evidences a fecal transmission route of their gut microbiota.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fiy002}, pmid = {29325007}, issn = {1574-6941}, abstract = {Eukaryotes have established symbiotic relationship with microorganisms, which enables them to accomplish functions that they cannot perform alone. In the German cockroach, Blattella germanica, the obligate endosymbiont Blattabacterium coexists with a rich gut microbiota. The transmission of Blattabacterium is vertical, but little is known about how the gut microbiota colonizes newborn individuals. In this study, we treated B. germanica populations with rifampicin, a broad-spectrum antibiotic, during two generations and analyzed gut bacterial composition and the Blattabacterium load in control and rifampicin-treated populations. Rifampicin exerted a drastic effect on gut microbiota composition, which recovered in the second generation in the case where the antibiotic was not added to the diet. Furthermore, we observed that bacterial species present in the diet, and particularly in the feces, contribute significantly to establishing the gut microbiota. Finally, the Blattabacterium population remained unaffected by the antibiotic treatment of adults during the first generation but was strongly reduced in the second generation, suggesting that this intracellular symbiont is sensitive to rifampicin only during the infection of the mature oocytes, when it is in an extracellular stage.}, } @article {pmid29324330, year = {2018}, author = {Holden, S}, title = {Probing the mechanistic principles of bacterial cell division with super-resolution microscopy.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {84-91}, doi = {10.1016/j.mib.2017.12.005}, pmid = {29324330}, issn = {1879-0364}, support = {206670/Z/17/Z//Wellcome Trust/United Kingdom ; }, mesh = {Bacteria/cytology/*ultrastructure ; *Bacterial Physiological Phenomena ; Bacterial Proteins/genetics/ultrastructure ; *Cell Division ; Cytoskeletal Proteins/genetics/ultrastructure ; Humans ; Microscopy/instrumentation/*methods ; }, abstract = {Bacterial cell division takes place almost entirely below the diffraction limit of light microscopy, making super-resolution microscopy ideally suited to interrogating this process. I review how super-resolution microscopy has advanced our understanding of bacterial cell division. I discuss the mechanistic implications of these findings, propose physical models for cell division compatible with recent data, and discuss key outstanding questions and future research directions.}, } @article {pmid29323331, year = {2018}, author = {Stephan, DW}, title = {Dogma-breaking catalysis.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {160-162}, doi = {10.1038/d41586-017-09006-6}, pmid = {29323331}, issn = {1476-4687}, } @article {pmid29323330, year = {2018}, author = {Popkin, G}, title = {Step aside CERN: There's a cheaper way to break open physics.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {142-144}, doi = {10.1038/d41586-018-00106-5}, pmid = {29323330}, issn = {1476-4687}, } @article {pmid29323329, year = {2018}, author = {Agarwal, J}, title = {Cometary spin-down.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {158-159}, doi = {10.1038/d41586-018-00008-6}, pmid = {29323329}, issn = {1476-4687}, mesh = {*Extraterrestrial Environment ; *Meteoroids ; }, } @article {pmid29323328, year = {2018}, author = {Scharf, C and Fischer, D and Meadows, V}, title = {Exoplanet science 2.0.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {149-151}, doi = {10.1038/d41586-018-00108-3}, pmid = {29323328}, issn = {1476-4687}, mesh = {Earth (Planet) ; Evolution, Chemical ; *Exobiology/economics/methods ; Extraterrestrial Environment/*chemistry ; Interdisciplinary Research ; Jupiter ; Mars ; Neptune ; *Planets ; Telescopes ; United States ; United States National Aeronautics and Space Administration ; }, } @article {pmid29323327, year = {2018}, author = {Shih, I}, title = {Indonesian scientists embrace preprint server.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {139}, doi = {10.1038/d41586-017-08838-6}, pmid = {29323327}, issn = {1476-4687}, mesh = {Bibliometrics ; Indonesia ; Internet/*statistics & numerical data ; Language ; *Open Access Publishing ; *Research/standards ; *Research Personnel/standards ; *Research Report/standards ; *Software ; }, } @article {pmid29323326, year = {2018}, author = {}, title = {Male scientists given more opportunities to address colloquia.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {241}, doi = {10.1038/d41586-018-00115-4}, pmid = {29323326}, issn = {1476-4687}, } @article {pmid29323325, year = {2018}, author = {Urnov, F}, title = {An ode to gene edits that prevent deafness.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {162-163}, doi = {10.1038/d41586-017-08645-z}, pmid = {29323325}, issn = {1476-4687}, mesh = {*Deafness ; *Gene Editing ; Humans ; }, } @article {pmid29323323, year = {2018}, author = {Saba, M}, title = {Rule-breaking perovskites.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {163-164}, doi = {10.1038/d41586-018-00012-w}, pmid = {29323323}, issn = {1476-4687}, } @article {pmid29323322, year = {2018}, author = {Emmons, SW}, title = {Neuronal plasticity in nematode worms.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {159-160}, doi = {10.1038/d41586-017-09031-5}, pmid = {29323322}, issn = {1476-4687}, mesh = {Animals ; Caenorhabditis elegans ; *Helminths ; Nematoda ; *Neuronal Plasticity ; }, } @article {pmid29323321, year = {2018}, author = {Sohn, E}, title = {When sickness interrupts science.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {239-241}, doi = {10.1038/d41586-018-00112-7}, pmid = {29323321}, issn = {1476-4687}, mesh = {Adaptation, Psychological ; Chronic Disease ; *Disabled Persons/psychology ; *Efficiency ; Female ; Humans ; *Research Personnel/psychology ; Self Care ; *Workload/psychology ; }, } @article {pmid29323320, year = {2018}, author = {Abderrahman, B and Jordan, VC}, title = {Telling details of breast-cancer recurrence.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {155}, doi = {10.1038/d41586-018-00399-6}, pmid = {29323320}, issn = {1476-4687}, mesh = {Breast ; Breast Neoplasms ; Humans ; *Neoplasm Recurrence, Local ; Recurrence ; }, } @article {pmid29323319, year = {2018}, author = {Castelvecchi, D}, title = {Silicon gains ground in quantum-computing race.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {136-137}, doi = {10.1038/d41586-018-00213-3}, pmid = {29323319}, issn = {1476-4687}, } @article {pmid29323318, year = {2018}, author = {}, title = {Protect the high seas from harm.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {127-128}, doi = {10.1038/d41586-018-00102-9}, pmid = {29323318}, issn = {1476-4687}, } @article {pmid29323317, year = {2018}, author = {Shotton, D}, title = {Funders should mandate open citations.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {129}, doi = {10.1038/d41586-018-00104-7}, pmid = {29323317}, issn = {1476-4687}, mesh = {Authorship ; *Bibliometrics ; Open Access Publishing/*economics/*trends ; *Research Support as Topic ; }, } @article {pmid29323316, year = {2018}, author = {Goodman, SN}, title = {A quality-control test for predatory journals.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {155}, doi = {10.1038/d41586-018-00403-z}, pmid = {29323316}, issn = {1476-4687}, mesh = {Open Access Publishing/legislation & jurisprudence/*standards ; Periodicals as Topic/legislation & jurisprudence/*standards ; *Quality Control ; Research/*standards ; }, } @article {pmid29323315, year = {2018}, author = {}, title = {Tumour lymph vessels boost immunotherapy.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {164}, doi = {10.1038/d41586-018-00414-w}, pmid = {29323315}, issn = {1476-4687}, } @article {pmid29323314, year = {2018}, author = {}, title = {Gender pay gap persists.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {241}, doi = {10.1038/d41586-018-00113-6}, pmid = {29323314}, issn = {1476-4687}, } @article {pmid29323313, year = {2018}, author = {}, title = {Mystery funders of Arecibo radio telescope can celebrate an early success.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {127}, doi = {10.1038/d41586-018-00100-x}, pmid = {29323313}, issn = {1476-4687}, } @article {pmid29323312, year = {2018}, author = {Palomo, I}, title = {Test climate targets using fragile ecosystems.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {155}, doi = {10.1038/d41586-018-00402-0}, pmid = {29323312}, issn = {1476-4687}, mesh = {*Climate ; Climate Change ; *Ecosystem ; }, } @article {pmid29323311, year = {2018}, author = {Schiermeier, Q}, title = {Germany vs Elsevier: universities win temporary journal access after refusing to pay fees.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {137}, doi = {10.1038/d41586-018-00093-7}, pmid = {29323311}, issn = {1476-4687}, mesh = {Access to Information/*legislation & jurisprudence ; Fees and Charges/*legislation & jurisprudence ; Germany ; Open Access Publishing/*legislation & jurisprudence ; Periodicals as Topic/*economics ; Universities/*economics ; }, } @article {pmid29323309, year = {2018}, author = {Thomas, J}, title = {Gene-drive e-mails were legally requested.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {155}, doi = {10.1038/d41586-017-08827-9}, pmid = {29323309}, issn = {1476-4687}, mesh = {*Electronic Mail ; Humans ; *Postal Service ; }, } @article {pmid29323308, year = {2018}, author = {Tollefson, J}, title = {Climate scientists unlock secrets of 'blue carbon'.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {139-140}, doi = {10.1038/d41586-018-00018-4}, pmid = {29323308}, issn = {1476-4687}, mesh = {Africa ; Carbon/*analysis ; Carbon Dioxide/analysis/chemistry ; *Carbon Sequestration ; Conservation of Natural Resources/economics/trends ; *Environmental Monitoring ; Soil/*chemistry ; United States ; United States Department of Agriculture ; United States National Aeronautics and Space Administration ; *Wetlands ; }, } @article {pmid29323307, year = {2018}, author = {}, title = {Images of the year.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {140}, doi = {10.1038/d41586-018-00384-z}, pmid = {29323307}, issn = {1476-4687}, } @article {pmid29323306, year = {2018}, author = {}, title = {Combinations on trial.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {155}, doi = {10.1038/d41586-018-00415-9}, pmid = {29323306}, issn = {1476-4687}, } @article {pmid29323304, year = {2018}, author = {Pickrell, J}, title = {Tooth scratches reveal new clues to pterosaur diets.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {138}, doi = {10.1038/d41586-018-00080-y}, pmid = {29323304}, issn = {1476-4687}, mesh = {Animals ; Diet/history/*veterinary ; Dinosaurs/*anatomy & histology/physiology ; Extinction, Biological ; Flight, Animal ; *Fossils ; History, Ancient ; Insecta ; Models, Biological ; *Tooth/anatomy & histology/diagnostic imaging ; Vertebrates ; }, } @article {pmid29323303, year = {2018}, author = {Shen, H}, title = {How to see a memory.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {146-148}, doi = {10.1038/d41586-018-00107-4}, pmid = {29323303}, issn = {1476-4687}, mesh = {Action Potentials ; Algorithms ; Amygdala/cytology/physiology ; Animals ; Brain/anatomy & histology/*cytology/*physiology ; Cyclic AMP Response Element-Binding Protein/metabolism ; Electric Stimulation ; Fear ; Hippocampus/cytology/physiology ; Humans ; Magnetic Resonance Imaging ; Memory Consolidation/*physiology ; Mice ; *Neuroimaging ; *Neuronal Plasticity ; Neurons/*metabolism ; Pattern Recognition, Automated ; Time Factors ; }, } @article {pmid29323302, year = {2018}, author = {}, title = {Typhoid vaccine, dementia research and discrimination in science.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {132-133}, doi = {10.1038/d41586-018-00105-6}, pmid = {29323302}, issn = {1476-4687}, } @article {pmid29323301, year = {2018}, author = {Witze, A}, title = {Scientific ballooning takes off.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {135-136}, doi = {10.1038/d41586-018-00017-5}, pmid = {29323301}, issn = {1476-4687}, } @article {pmid29323300, year = {2018}, author = {}, title = {Chemists go green to make better blue jeans.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {128}, doi = {10.1038/d41586-018-00103-8}, pmid = {29323300}, issn = {1476-4687}, } @article {pmid29323299, year = {2018}, author = {Smit, R and Bouwens, RJ and Carniani, S and Oesch, PA and Labbé, I and Illingworth, GD and van der Werf, P and Bradley, LD and Gonzalez, V and Hodge, JA and Holwerda, BW and Maiolino, R and Zheng, W}, title = {Rotation in [C ii]-emitting gas in two galaxies at a redshift of 6.8.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {178-181}, pmid = {29323299}, issn = {1476-4687}, abstract = {The earliest galaxies are thought to have emerged during the first billion years of cosmic history, initiating the ionization of the neutral hydrogen that pervaded the Universe at this time. Studying this 'epoch of reionization' involves looking for the spectral signatures of ancient galaxies that are, owing to the expansion of the Universe, now very distant from Earth and therefore exhibit large redshifts. However, finding these spectral fingerprints is challenging. One spectral characteristic of ancient and distant galaxies is strong hydrogen-emission lines (known as Lyman-α lines), but the neutral intergalactic medium that was present early in the epoch of reionization scatters such Lyman-α photons. Another potential spectral identifier is the line at wavelength 157.4 micrometres of the singly ionized state of carbon (the [C ii] λ = 157.74 μm line), which signifies cooling gas and is expected to have been bright in the early Universe. However, so far Lyman-α-emitting galaxies from the epoch of reionization have demonstrated much fainter [C ii] luminosities than would be expected from local scaling relations, and searches for the [C ii] line in sources without Lyman-α emission but with photometric redshifts greater than 6 (corresponding to the first billion years of the Universe) have been unsuccessful. Here we identify [C ii] λ = 157.74 μm emission from two sources that we selected as high-redshift candidates on the basis of near-infrared photometry; we confirm that these sources are two galaxies at redshifts of z = 6.8540 ± 0.0003 and z = 6.8076 ± 0.0002. Notably, the luminosity of the [C ii] line from these galaxies is higher than that found previously in star-forming galaxies with redshifts greater than 6.5. The luminous and extended [C ii] lines reveal clear velocity gradients that, if interpreted as rotation, would indicate that these galaxies have similar dynamic properties to the turbulent yet rotation-dominated disks that have been observed in Hα-emitting galaxies two billion years later, at 'cosmic noon'.}, } @article {pmid29323298, year = {2018}, author = {Frattini, V and Pagnotta, SM and Tala, and Fan, JJ and Russo, MV and Lee, SB and Garofano, L and Zhang, J and Shi, P and Lewis, G and Sanson, H and Frederick, V and Castano, AM and Cerulo, L and Rolland, DCM and Mall, R and Mokhtari, K and Elenitoba-Johnson, KSJ and Sanson, M and Huang, X and Ceccarelli, M and Lasorella, A and Iavarone, A}, title = {A metabolic function of FGFR3-TACC3 gene fusions in cancer.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {222-227}, pmid = {29323298}, issn = {1476-4687}, support = {R01 CA179044/CA/NCI NIH HHS/United States ; R01 CA131126/CA/NCI NIH HHS/United States ; R01 CA178546/CA/NCI NIH HHS/United States ; R01 CA190891/CA/NCI NIH HHS/United States ; R01 CA101644/CA/NCI NIH HHS/United States ; T32 CA009503/CA/NCI NIH HHS/United States ; U54 CA193313/CA/NCI NIH HHS/United States ; R01 NS061776/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Brain/drug effects/metabolism/pathology ; Cell Line, Tumor ; *Cell Respiration/drug effects ; Cell Transformation, Neoplastic/drug effects ; Female ; Glioblastoma/drug therapy/genetics/metabolism/pathology ; Humans ; Male ; Mice ; Microtubule-Associated Proteins/*genetics ; Mitochondria/drug effects/genetics/*metabolism ; NIMA-Interacting Peptidylprolyl Isomerase/chemistry/metabolism ; Neoplasms/drug therapy/*genetics/*metabolism/pathology ; Oncogene Proteins, Fusion/*genetics ; Organelle Biogenesis ; Oxidative Phosphorylation/drug effects ; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha/metabolism ; Peroxisomes/drug effects/metabolism ; Phosphorylation ; Protein Biosynthesis ; Reactive Oxygen Species/metabolism ; Receptor, Fibroblast Growth Factor, Type 3/*genetics ; Receptors, Estrogen/metabolism ; Transcription, Genetic ; Xenograft Model Antitumor Assays ; }, abstract = {Chromosomal translocations that generate in-frame oncogenic gene fusions are notable examples of the success of targeted cancer therapies. We have previously described gene fusions of FGFR3-TACC3 (F3-T3) in 3% of human glioblastoma cases. Subsequent studies have reported similar frequencies of F3-T3 in many other cancers, indicating that F3-T3 is a commonly occuring fusion across all tumour types. F3-T3 fusions are potent oncogenes that confer sensitivity to FGFR inhibitors, but the downstream oncogenic signalling pathways remain unknown. Here we show that human tumours with F3-T3 fusions cluster within transcriptional subgroups that are characterized by the activation of mitochondrial functions. F3-T3 activates oxidative phosphorylation and mitochondrial biogenesis and induces sensitivity to inhibitors of oxidative metabolism. Phosphorylation of the phosphopeptide PIN4 is an intermediate step in the signalling pathway of the activation of mitochondrial metabolism. The F3-T3-PIN4 axis triggers the biogenesis of peroxisomes and the synthesis of new proteins. The anabolic response converges on the PGC1α coactivator through the production of intracellular reactive oxygen species, which enables mitochondrial respiration and tumour growth. These data illustrate the oncogenic circuit engaged by F3-T3 and show that F3-T3-positive tumours rely on mitochondrial respiration, highlighting this pathway as a therapeutic opportunity for the treatment of tumours with F3-T3 fusions. We also provide insights into the genetic alterations that initiate the chain of metabolic responses that drive mitochondrial metabolism in cancer.}, } @article {pmid29323297, year = {2018}, author = {Michilli, D and Seymour, A and Hessels, JWT and Spitler, LG and Gajjar, V and Archibald, AM and Bower, GC and Chatterjee, S and Cordes, JM and Gourdji, K and Heald, GH and Kaspi, VM and Law, CJ and Sobey, C and Adams, EAK and Bassa, CG and Bogdanov, S and Brinkman, C and Demorest, P and Fernandez, F and Hellbourg, G and Lazio, TJW and Lynch, RS and Maddox, N and Marcote, B and McLaughlin, MA and Paragi, Z and Ransom, SM and Scholz, P and Siemion, APV and Tendulkar, SP and Van Rooy, P and Wharton, RS and Whitlow, D}, title = {An extreme magneto-ionic environment associated with the fast radio burst source FRB 121102.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {182-185}, pmid = {29323297}, issn = {1476-4687}, abstract = {Fast radio bursts are millisecond-duration, extragalactic radio flashes of unknown physical origin. The only known repeating fast radio burst source-FRB 121102-has been localized to a star-forming region in a dwarf galaxy at redshift 0.193 and is spatially coincident with a compact, persistent radio source. The origin of the bursts, the nature of the persistent source and the properties of the local environment are still unclear. Here we report observations of FRB 121102 that show almost 100 per cent linearly polarized emission at a very high and variable Faraday rotation measure in the source frame (varying from +1.46 × 105 radians per square metre to +1.33 × 105 radians per square metre at epochs separated by seven months) and narrow (below 30 microseconds) temporal structure. The large and variable rotation measure demonstrates that FRB 121102 is in an extreme and dynamic magneto-ionic environment, and the short durations of the bursts suggest a neutron star origin. Such large rotation measures have hitherto been observed only in the vicinities of massive black holes (larger than about 10,000 solar masses). Indeed, the properties of the persistent radio source are compatible with those of a low-luminosity, accreting massive black hole. The bursts may therefore come from a neutron star in such an environment or could be explained by other models, such as a highly magnetized wind nebula or supernova remnant surrounding a young neutron star.}, } @article {pmid29323296, year = {2018}, author = {Bodewits, D and Farnham, TL and Kelley, MSP and Knight, MM}, title = {A rapid decrease in the rotation rate of comet 41P/Tuttle-Giacobini-Kresák.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {186-188}, pmid = {29323296}, issn = {1476-4687}, abstract = {Cometary outgassing can produce torques that change the spin state of the cometary nucleus, which in turn influences the evolution and lifetime of the comet. If these torques increase the rate of rotation to the extent that centripetal forces exceed the material strength of the nucleus, the comet can fragment. Torques that slow down the rotation can cause the spin state to become unstable, but if the torques persist the nucleus can eventually reorient itself and the rotation rate can increase again. Simulations predict that most comets go through a short phase of rapid changes in spin state, after which changes occur gradually over longer times. Here we report observations of comet 41P/Tuttle-Giacobini-Kresák during its close approach to Earth (0.142 astronomical units, approximately 21 million kilometres, on 1 April 2017) that reveal a rapid decrease in rotation rate. Between March and May 2017, the apparent rotation period of the nucleus increased from 20 hours to more than 46 hours-a rate of change of more than an order of magnitude larger than has hitherto been measured. This phenomenon must have been caused by the gas emission from the comet aligning in such a way that it produced an anomalously strong torque that slowed the spin rate of the nucleus. The behaviour of comet 41P/Tuttle-Giacobini-Kresák suggests that it is in a distinct evolutionary state and that its rotation may be approaching the point of instability.}, } @article {pmid29323295, year = {2018}, author = {Garaycoechea, JI and Crossan, GP and Langevin, F and Mulderrig, L and Louzada, S and Yang, F and Guilbaud, G and Park, N and Roerink, S and Nik-Zainal, S and Stratton, MR and Patel, KJ}, title = {Alcohol and endogenous aldehydes damage chromosomes and mutate stem cells.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {171-177}, pmid = {29323295}, issn = {1476-4687}, support = {//Wellcome Trust/United Kingdom ; MC_U105178811//Medical Research Council/United Kingdom ; }, mesh = {Acetaldehyde/*metabolism ; Alcohol Dehydrogenase/deficiency/genetics/metabolism ; Animals ; Cell Survival/drug effects ; DNA Breaks, Double-Stranded/*drug effects ; DNA End-Joining Repair ; Ethanol/administration & dosage/*metabolism/*pharmacology ; Fanconi Anemia/genetics/metabolism/pathology ; Fanconi Anemia Complementation Group D2 Protein/deficiency/genetics/metabolism ; Female ; Gene Deletion ; Genes, p53/genetics ; Genomic Instability/*drug effects ; Hematopoietic Stem Cell Transplantation ; Hematopoietic Stem Cells/*drug effects/metabolism/*pathology ; Ku Autoantigen/metabolism ; Male ; Mice ; Mice, Inbred C57BL ; *Mutation ; Recombinational DNA Repair/drug effects ; Tumor Suppressor Protein p53/deficiency/genetics/metabolism ; Whole Genome Sequencing ; }, abstract = {Haematopoietic stem cells renew blood. Accumulation of DNA damage in these cells promotes their decline, while misrepair of this damage initiates malignancies. Here we describe the features and mutational landscape of DNA damage caused by acetaldehyde, an endogenous and alcohol-derived metabolite. This damage results in DNA double-stranded breaks that, despite stimulating recombination repair, also cause chromosome rearrangements. We combined transplantation of single haematopoietic stem cells with whole-genome sequencing to show that this damage occurs in stem cells, leading to deletions and rearrangements that are indicative of microhomology-mediated end-joining repair. Moreover, deletion of p53 completely rescues the survival of aldehyde-stressed and mutated haematopoietic stem cells, but does not change the pattern or the intensity of genome instability within individual stem cells. These findings characterize the mutation of the stem-cell genome by an alcohol-derived and endogenous source of DNA damage. Furthermore, we identify how the choice of DNA-repair pathway and a stringent p53 response limit the transmission of aldehyde-induced mutations in stem cells.}, } @article {pmid29323294, year = {2018}, author = {Moreno-Mayar, JV and Potter, BA and Vinner, L and Steinrücken, M and Rasmussen, S and Terhorst, J and Kamm, JA and Albrechtsen, A and Malaspinas, AS and Sikora, M and Reuther, JD and Irish, JD and Malhi, RS and Orlando, L and Song, YS and Nielsen, R and Meltzer, DJ and Willerslev, E}, title = {Terminal Pleistocene Alaskan genome reveals first founding population of Native Americans.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {203-207}, pmid = {29323294}, issn = {1476-4687}, support = {R01 GM094402/GM/NIGMS NIH HHS/United States ; }, mesh = {Alaska ; Far East/ethnology ; *Founder Effect ; Gene Flow ; Genetics, Population ; Genome, Human/*genetics ; History, Ancient ; Human Migration ; Humans ; Indians, North American/*genetics ; Infant ; *Models, Genetic ; *Phylogeny ; Rivers ; Siberia/ethnology ; Time Factors ; }, abstract = {Despite broad agreement that the Americas were initially populated via Beringia, the land bridge that connected far northeast Asia with northwestern North America during the Pleistocene epoch, when and how the peopling of the Americas occurred remains unresolved. Analyses of human remains from Late Pleistocene Alaska are important to resolving the timing and dispersal of these populations. The remains of two infants were recovered at Upward Sun River (USR), and have been dated to around 11.5 thousand years ago (ka). Here, by sequencing the USR1 genome to an average coverage of approximately 17 times, we show that USR1 is most closely related to Native Americans, but falls basal to all previously sequenced contemporary and ancient Native Americans. As such, USR1 represents a distinct Ancient Beringian population. Using demographic modelling, we infer that the Ancient Beringian population and ancestors of other Native Americans descended from a single founding population that initially split from East Asians around 36 ± 1.5 ka, with gene flow persisting until around 25 ± 1.1 ka. Gene flow from ancient north Eurasians into all Native Americans took place 25-20 ka, with Ancient Beringians branching off around 22-18.1 ka. Our findings support a long-term genetic structure in ancestral Native Americans, consistent with the Beringian 'standstill model'. We show that the basal northern and southern Native American branches, to which all other Native Americans belong, diverged around 17.5-14.6 ka, and that this probably occurred south of the North American ice sheets. We also show that after 11.5 ka, some of the northern Native American populations received gene flow from a Siberian population most closely related to Koryaks, but not Palaeo-Eskimos, Inuits or Kets, and that Native American gene flow into Inuits was through northern and not southern Native American groups. Our findings further suggest that the far-northern North American presence of northern Native Americans is from a back migration that replaced or absorbed the initial founding population of Ancient Beringians.}, } @article {pmid29323293, year = {2018}, author = {Zhu, W and Winter, MG and Byndloss, MX and Spiga, L and Duerkop, BA and Hughes, ER and Büttner, L and de Lima Romão, E and Behrendt, CL and Lopez, CA and Sifuentes-Dominguez, L and Huff-Hardy, K and Wilson, RP and Gillis, CC and Tükel, Ç and Koh, AY and Burstein, E and Hooper, LV and Bäumler, AJ and Winter, SE}, title = {Precision editing of the gut microbiota ameliorates colitis.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {208-211}, pmid = {29323293}, issn = {1476-4687}, support = {R01 AI118807/AI/NIAID NIH HHS/United States ; K01 DK102436/DK/NIDDK NIH HHS/United States ; R21 AI128151/AI/NIAID NIH HHS/United States ; R01 DK070855/DK/NIDDK NIH HHS/United States ; T32 DK007745/DK/NIDDK NIH HHS/United States ; T32 AI007520/AI/NIAID NIH HHS/United States ; R01 AI112445/AI/NIAID NIH HHS/United States ; K12 HD068369/HD/NICHD NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Anaerobiosis/drug effects ; Animals ; Cell Respiration/drug effects ; Colitis/*drug therapy/*microbiology ; Dysbiosis/drug therapy/microbiology ; Enterobacteriaceae/drug effects/growth & development/metabolism ; Female ; Gastrointestinal Microbiome/*drug effects ; Inflammation/drug therapy/microbiology/pathology ; Intestinal Mucosa/drug effects/microbiology/pathology ; Intestines/*drug effects/*microbiology/pathology ; Male ; Mice ; Mice, Inbred C57BL ; Molybdenum/metabolism ; Tungsten Compounds/pharmacology/therapeutic use ; }, abstract = {Inflammatory diseases of the gastrointestinal tract are frequently associated with dysbiosis, characterized by changes in gut microbial communities that include an expansion of facultative anaerobic bacteria of the Enterobacteriaceae family (phylum Proteobacteria). Here we show that a dysbiotic expansion of Enterobacteriaceae during gut inflammation could be prevented by tungstate treatment, which selectively inhibited molybdenum-cofactor-dependent microbial respiratory pathways that are operational only during episodes of inflammation. By contrast, we found that tungstate treatment caused minimal changes in the microbiota composition under homeostatic conditions. Notably, tungstate-mediated microbiota editing reduced the severity of intestinal inflammation in mouse models of colitis. We conclude that precision editing of the microbiota composition by tungstate treatment ameliorates the adverse effects of dysbiosis in the inflamed gut.}, } @article {pmid29323292, year = {2018}, author = {Becker, MA and Vaxenburg, R and Nedelcu, G and Sercel, PC and Shabaev, A and Mehl, MJ and Michopoulos, JG and Lambrakos, SG and Bernstein, N and Lyons, JL and Stöferle, T and Mahrt, RF and Kovalenko, MV and Norris, DJ and Rainò, G and Efros, AL}, title = {Bright triplet excitons in caesium lead halide perovskites.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {189-193}, pmid = {29323292}, issn = {1476-4687}, abstract = {Nanostructured semiconductors emit light from electronic states known as excitons. For organic materials, Hund's rules state that the lowest-energy exciton is a poorly emitting triplet state. For inorganic semiconductors, similar rules predict an analogue of this triplet state known as the 'dark exciton'. Because dark excitons release photons slowly, hindering emission from inorganic nanostructures, materials that disobey these rules have been sought. However, despite considerable experimental and theoretical efforts, no inorganic semiconductors have been identified in which the lowest exciton is bright. Here we show that the lowest exciton in caesium lead halide perovskites (CsPbX3, with X = Cl, Br or I) involves a highly emissive triplet state. We first use an effective-mass model and group theory to demonstrate the possibility of such a state existing, which can occur when the strong spin-orbit coupling in the conduction band of a perovskite is combined with the Rashba effect. We then apply our model to CsPbX3 nanocrystals, and measure size- and composition-dependent fluorescence at the single-nanocrystal level. The bright triplet character of the lowest exciton explains the anomalous photon-emission rates of these materials, which emit about 20 and 1,000 times faster than any other semiconductor nanocrystal at room and cryogenic temperatures, respectively. The existence of this bright triplet exciton is further confirmed by analysis of the fine structure in low-temperature fluorescence spectra. For semiconductor nanocrystals, which are already used in lighting, lasers and displays, these excitons could lead to materials with brighter emission. More generally, our results provide criteria for identifying other semiconductors that exhibit bright excitons, with potential implications for optoelectronic devices.}, } @article {pmid29323291, year = {2018}, author = {Hart, MP and Hobert, O}, title = {Neurexin controls plasticity of a mature, sexually dimorphic neuron.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {165-170}, pmid = {29323291}, issn = {1476-4687}, support = {2R37NS039996/NH/NIH HHS/United States ; F32 NS086285/NS/NINDS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R37 NS039996/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*cytology/*physiology ; Caenorhabditis elegans Proteins/*metabolism ; Cell Adhesion Molecules, Neuronal/*metabolism ; GABAergic Neurons/cytology/*metabolism ; Hermaphroditic Organisms/physiology ; Male ; Neurites/metabolism ; Neuronal Plasticity/*physiology ; *Sex Characteristics ; Sexual Behavior, Animal/physiology ; Synapses/metabolism ; gamma-Aminobutyric Acid/metabolism ; }, abstract = {During development and adulthood, brain plasticity is evident at several levels, from synaptic structure and function to the outgrowth of dendrites and axons. Whether and how sex impinges on neuronal plasticity is poorly understood. Here we show that the sex-shared GABA (γ-aminobutyric acid)-releasing DVB neuron in Caenorhabditis elegans displays experience-dependent and sexually dimorphic morphological plasticity, characterized by the stochastic and dynamic addition of multiple neurites in adult males. These added neurites enable synaptic rewiring of the DVB neuron and instruct a functional switch of the neuron that directly modifies a step of male mating behaviour. Both DVB neuron function and male mating behaviour can be altered by experience and by manipulation of postsynaptic activity. The outgrowth of DVB neurites is promoted by presynaptic neurexin and antagonized by postsynaptic neuroligin, revealing a non-conventional activity and mode of interaction of these conserved, human-disease-relevant factors.}, } @article {pmid29323290, year = {2018}, author = {Rodriguez-Fraticelli, AE and Wolock, SL and Weinreb, CS and Panero, R and Patel, SH and Jankovic, M and Sun, J and Calogero, RA and Klein, AM and Camargo, FD}, title = {Clonal analysis of lineage fate in native haematopoiesis.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {212-216}, pmid = {29323290}, issn = {1476-4687}, support = {/HHMI/Howard Hughes Medical Institute/United States ; T32 GM080177/GM/NIGMS NIH HHS/United States ; R01 HL128850/HL/NHLBI NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; P01 HL131477/HL/NHLBI NIH HHS/United States ; U54 DK110805/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; *Cell Lineage ; Clone Cells/*cytology/metabolism ; Female ; *Hematopoiesis ; Hematopoietic Stem Cells/cytology/metabolism ; Male ; Megakaryocytes/cytology/metabolism ; Mice ; Multipotent Stem Cells/cytology/metabolism ; Sequence Analysis, RNA ; Single-Cell Analysis ; Transcriptome/genetics ; }, abstract = {Haematopoiesis, the process of mature blood and immune cell production, is functionally organized as a hierarchy, with self-renewing haematopoietic stem cells and multipotent progenitor cells sitting at the very top. Multiple models have been proposed as to what the earliest lineage choices are in these primitive haematopoietic compartments, the cellular intermediates, and the resulting lineage trees that emerge from them. Given that the bulk of studies addressing lineage outcomes have been performed in the context of haematopoietic transplantation, current models of lineage branching are more likely to represent roadmaps of lineage potential than native fate. Here we use transposon tagging to clonally trace the fates of progenitors and stem cells in unperturbed haematopoiesis. Our results describe a distinct clonal roadmap in which the megakaryocyte lineage arises largely independently of other haematopoietic fates. Our data, combined with single-cell RNA sequencing, identify a functional hierarchy of unilineage- and oligolineage-producing clones within the multipotent progenitor population. Finally, our results demonstrate that traditionally defined long-term haematopoietic stem cells are a significant source of megakaryocyte-restricted progenitors, suggesting that the megakaryocyte lineage is the predominant native fate of long-term haematopoietic stem cells. Our study provides evidence for a substantially revised roadmap for unperturbed haematopoiesis, and highlights unique properties of multipotent progenitors and haematopoietic stem cells in situ.}, } @article {pmid29322681, year = {2018}, author = {Maji, A and Misra, R and Dhakan, DB and Gupta, V and Mahato, NK and Saxena, R and Mittal, P and Thukral, N and Sharma, E and Singh, A and Virmani, R and Gaur, M and Singh, H and Hasija, Y and Arora, G and Agrawal, A and Chaudhry, A and Khurana, JP and Sharma, VK and Lal, R and Singh, Y}, title = {Gut microbiome contributes to impairment of immunity in pulmonary tuberculosis patients by alteration of butyrate and propionate producers.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {402-419}, doi = {10.1111/1462-2920.14015}, pmid = {29322681}, issn = {1462-2920}, abstract = {Tuberculosis (TB) is primarily associated with decline in immune health status. As gut microbiome (GM) is implicated in the regulation of host immunity and metabolism, here we investigate GM alteration in TB patients by 16S rRNA gene and whole-genome shotgun sequencing. The study group constituted of patients with pulmonary TB and their healthy household contacts as controls (HCs). Significant alteration of microbial taxonomic and functional capacity was observed in patients with active TB as compared to the HCs. We observed that Prevotella and Bifidobacterium abundance were associated with HCs, whereas butyrate and propionate-producing bacteria like Faecalibacterium, Roseburia, Eubacterium and Phascolarctobacterium were significantly enriched in TB patients. Functional analysis showed reduced biosynthesis of vitamins and amino acids in favour of enriched metabolism of butyrate and propionate in TB subjects. The TB subjects were also investigated during the course of treatment, to analyse the variation of GM. Although perturbation in microbial composition was still evident after a month's administration of anti-TB drugs, significant changes were observed in metagenome gene pool that pointed towards recovery in functional capacity. Therefore, the findings from this pilot study suggest that microbial dysbiosis may contribute to pathophysiology of TB by enhancing the anti-inflammatory milieu in the host.}, } @article {pmid29322680, year = {2018}, author = {Wackett, LP}, title = {Microbial chemotaxis in the environment: An annotated selection of World Wide Web sites relevant to the topics in environmental microbiology.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {420-421}, doi = {10.1111/1462-2920.14038}, pmid = {29322680}, issn = {1462-2920}, } @article {pmid29322640, year = {2018}, author = {Smith, CR and Morandin, C and Noureddine, M and Pant, S}, title = {Conserved roles of Osiris genes in insect development, polymorphism and protection.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {516-529}, doi = {10.1111/jeb.13238}, pmid = {29322640}, issn = {1420-9101}, abstract = {Much of the variation among insects is derived from the different ways that chitin has been moulded to form rigid structures, both internal and external. In this study, we identify a highly conserved expression pattern in an insect-only gene family, the Osiris genes, that is essential for development, but also plays a significant role in phenotypic plasticity and in immunity/toxicity responses. The majority of Osiris genes exist in a highly syntenic cluster, and the cluster itself appears to have arisen very early in the evolution of insects. We used developmental gene expression in the fruit fly, Drosophila melanogaster, the bumble bee, Bombus terrestris, the harvester ant, Pogonomyrmex barbatus, and the wood ant, Formica exsecta, to compare patterns of Osiris gene expression both during development and between alternate caste phenotypes in the polymorphic social insects. Developmental gene expression of Osiris genes is highly conserved across species and correlated with gene location and evolutionary history. The social insect castes are highly divergent in pupal Osiris gene expression. Sets of co-expressed genes that include Osiris genes are enriched in gene ontology terms related to chitin/cuticle and peptidase activity. Osiris genes are essential for cuticle formation in both embryos and pupae, and genes co-expressed with Osiris genes affect wing development. Additionally, Osiris genes and those co-expressed seem to play a conserved role in insect toxicology defences and digestion. Given their role in development, plasticity, and protection, we propose that the Osiris genes play a central role in insect adaptive evolution.}, } @article {pmid29322618, year = {2018}, author = {Kato, S and Shibuya, T and Takaki, Y and Hirai, M and Nunoura, T and Suzuki, K}, title = {Genome-enabled metabolic reconstruction of dominant chemosynthetic colonizers in deep-sea massive sulfide deposits.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {862-877}, doi = {10.1111/1462-2920.14032}, pmid = {29322618}, issn = {1462-2920}, abstract = {Deep-sea massive sulfide deposits remaining after ceasing of hydrothermal activity potentially provide energy for a chemosynthetic ecosystem in the dark, cold marine environments. Although yet-uncultivated bacteria in the phylum Nitrospirae and the class Deltaproteobacteria are known to dominate the microbial communities of sulfide deposits at and below the seafloor, their metabolic capabilities remain largely elusive. Here, we reveal the metabolic potential of these yet-uncultivated bacteria in hydrothermally inactive sulfide deposits collected at the Southern Mariana Trough by seafloor drilling. Near-complete genomes of the predominant bacterial members were recovered from shotgun metagenomic sequences. The genomic capabilities for CO2 and N2 fixation suggest that these bacteria are primary producers in the microbial ecosystem. Their genomes also encode versatile chemolithotrophic energy metabolisms, such as the oxidation of H2 , sulfide and intermediate sulfur species including thiosulfate, all of which can be supplied by chemical reactions between seawater and metal sulfides. Notably, the presence of genes involved in thiosulfate oxidation in Nitrospirae and Deltaproteobacteria genomes is unusual. Our study strongly support the presence of a chemosynthetic ecosystem fuelled by the Earth's internal energy in the deep-sea massive sulfide deposits, and illustrates the unexpected metabolic capability of known bacterial taxonomic groups.}, } @article {pmid29322241, year = {2018}, author = {Chen, S and Sun, S and Xu, Y and Lv, J and Chen, L and Liu, L}, title = {Halorubrum depositum sp. nov., a Novel Halophilic Archaeon Isolated from a Salt Deposit.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {677-683}, pmid = {29322241}, issn = {1432-0991}, support = {31460003//the National Natural Science Foundation of China/ ; 591601//Anhui Provincial Key Lab. of the Conservation and Exploitation of Biological Resources (P. R. China)/ ; KJ2017A318//Anhui Provincial Natural Science Research Project (P. R. China)/ ; gxyqZD2017011//the Education Department of Anhui province (P. R. China)/ ; }, mesh = {Base Composition/genetics ; DNA, Archaeal/genetics ; Halorubrum/genetics/*isolation & purification/*metabolism ; Hydrogen-Ion Concentration ; Phosphatidylglycerols/metabolism ; RNA, Ribosomal, 16S/genetics ; Temperature ; }, abstract = {A non-motile, pleomorphic rod-shaped or oval, red-pigmented (nearly scarlet), extremely halophilic archaeon, strain Y78T, was isolated from a salt deposit of Yunnan salt mine, China. Analysis of the 16S rRNA gene sequence showed that it was phylogenetically related to species of the genus Halorubrum, with a close relationship to Halorubrum rutilum YJ-18-S1T (98.6%), Halorubrum yunnanense Q85T (98.3%), and Halorubrum lipolyticum 9-3T (98.1%). The temperature, NaCl, and pH ranges for growth were 25-50 °C, 12-30% (w/v), and 6.5-9.0, respectively. Mg2+ was required for growth. The polar lipids of strain Y78T were phosphatidylglycerol, phosphatidylglycerol phosphate methyl ester, phosphatidylglycerol sulfate, and a sulfated diglycosyl diether. The DNA G+C content was 66.6 mol%. DNA-DNA hybridization values between strain Y78T and two closely related species of the genus Halorubrum were far below 70%. Based on the data presented in this study, strain Y78T represents a novel species for which the name Halorubrum depositum sp. nov. is proposed; the type strain is Y78T (= CGMCC 1.15456T = JCM 31272T).}, } @article {pmid29321917, year = {2018}, author = {}, title = {Corrigendum.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {826}, doi = {10.1002/ece3.3769}, pmid = {29321917}, issn = {2045-7758}, abstract = {[This corrects the article DOI: 10.1002/ece3.1879.].}, } @article {pmid29321916, year = {2018}, author = {Suzuki, R and Matsubayashi, S and Saito, F and Murate, T and Masuda, T and Yamamoto, K and Kojima, R and Nakadai, K and Okuno, HG}, title = {A spatiotemporal analysis of acoustic interactions between great reed warblers (Acrocephalus arundinaceus) using microphone arrays and robot audition software HARK.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {812-825}, pmid = {29321916}, issn = {2045-7758}, abstract = {Acoustic interactions are important for understanding intra- and interspecific communication in songbird communities from the viewpoint of soundscape ecology. It has been suggested that birds may divide up sound space to increase communication efficiency in such a manner that they tend to avoid overlap with other birds when they sing. We are interested in clarifying the dynamics underlying the process as an example of complex systems based on short-term behavioral plasticity. However, it is very problematic to manually collect spatiotemporal patterns of acoustic events in natural habitats using data derived from a standard single-channel recording of several species singing simultaneously. Our purpose here was to investigate fine-scale spatiotemporal acoustic interactions of the great reed warbler. We surveyed spatial and temporal patterns of several vocalizing color-banded great reed warblers (Acrocephalus arundinaceus) using an open-source software for robot audition HARK (Honda Research Institute Japan Audition for Robots with Kyoto University) and three new 16-channel, stand-alone, and water-resistant microphone arrays, named DACHO spread out in the bird's habitat. We first show that our system estimated the location of two color-banded individuals' song posts with mean error distance of 5.5 ± 4.5 m from the location of observed song posts. We then evaluated the temporal localization accuracy of the songs by comparing the duration of localized songs around the song posts with those annotated by human observers, with an accuracy score of average 0.89 for one bird that stayed at one song post. We further found significant temporal overlap avoidance and an asymmetric relationship between songs of the two singing individuals, using transfer entropy. We believe that our system and analytical approach contribute to a better understanding of fine-scale acoustic interactions in time and space in bird communities.}, } @article {pmid29321915, year = {2018}, author = {Andersen, JC and Mills, NJ}, title = {Comparative genetics of invasive populations of walnut aphid, Chromaphis juglandicola, and its introduced parasitoid, Trioxys pallidus, in California.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {801-811}, pmid = {29321915}, issn = {2045-7758}, abstract = {Coevolution may be an important component of the sustainability of importation biological control, but how frequently introduced natural enemies coevolve with their target pests is unclear. Here we explore whether comparative population genetics of the invasive walnut aphid, Chromaphis juglandicola, and its introduced parasitoid, Trioxys pallidus, provide insights into the localized breakdown of biological control services in walnut orchards in California. We found that sampled populations of C. juglandicola exhibited higher estimates of genetic differentiation (FST) than co-occurring populations of T. pallidus. In contrast, estimates of both the inbreeding coefficient (GIS) and contemporary gene flow were higher for T. pallidus than for C. juglandicola. We also found evidence of reciprocal outlier loci in some locations, but none showed significant signatures of selection. Synthesis and applications. Understanding the importance of coevolutionary interactions for the sustainability of biological control remains an important and understudied component of biological control research. Given the observed differences in gene flow and genetic differentiation among populations of T. pallidus and C. juglandicola, we suspect that temporary local disruption of biological control services may occur more frequently than expected while remaining stable at broader regional scales. Further research that combines genomewide single nucleotide polymorphism genotyping with measurements of phenotypic traits is needed to provide more conclusive evidence of whether the occurrence of outlier loci that display significant signatures of selection can be interpreted as evidence of the presence of a geographic mosaic of coevolution in this system.}, } @article {pmid29321914, year = {2018}, author = {McDermott, PL and Wikle, CK and Millspaugh, J}, title = {A hierarchical spatiotemporal analog forecasting model for count data.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {790-800}, pmid = {29321914}, issn = {2045-7758}, abstract = {Analog forecasting is a mechanism-free nonlinear method that forecasts a system forward in time by examining how past states deemed similar to the current state moved forward. Previous applications of analog forecasting has been successful at producing robust forecasts for a variety of ecological and physical processes, but it has typically been presented in an empirical or heuristic procedure, rather than as a formal statistical model. The methodology presented here extends the model-based analog method of McDermott and Wikle (Environmetrics, 27, 2016, 70) by placing analog forecasting within a fully hierarchical statistical framework that can accommodate count observations. Using a Bayesian approach, the hierarchical analog model is able to quantify rigorously the uncertainty associated with forecasts. Forecasting waterfowl settling patterns in the northwestern United States and Canada is conducted by applying the hierarchical analog model to a breeding population survey dataset. Sea surface temperature (SST) in the Pacific Ocean is used to help identify potential analogs for the waterfowl settling patterns.}, } @article {pmid29321913, year = {2018}, author = {Cogliati, KM and Unrein, JR and Stewart, HA and Schreck, CB and Noakes, DLG}, title = {Egg size and emergence timing affect morphology and behavior in juvenile Chinook Salmon, Oncorhynchus tshawytscha.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {778-789}, pmid = {29321913}, issn = {2045-7758}, abstract = {Variation in early life history traits often leads to differentially expressed morphological and behavioral phenotypes. We investigated whether variation in egg size and emergence timing influence subsequent morphology associated with migration timing in juvenile spring Chinook Salmon, Oncorhynchus tshawytscha. Based on evidence for a positive relationship between growth rate and migration timing, we predicted that fish from small eggs and fish that emerged earlier would have similar morphology to fall migrants, while fish from large eggs and individuals that emerged later would be more similar to older spring yearling migrants. We sorted eyed embryos within females into two size categories: small and large. We collected early and late-emerging juveniles from each egg size category. We used landmark-based geometric morphometrics and found that egg size appears to drive morphological differences. Egg size shows evidence for an absolute rather than relative effect on body morphology. Fish from small eggs were morphologically more similar to fall migrants, while fish from large eggs were morphologically more similar to older spring yearling migrants. Previous research has shown that the body morphology of fish that prefer the surface or bottom location in a tank soon after emergence also correlates with the morphological variations between wild fall and spring migrants, respectively. We found that late-emerging fish spent more time near the surface. Our study shows that subtle differences in early life history characteristics may correlate with a diversity of future phenotypes.}, } @article {pmid29321912, year = {2018}, author = {Bloom, TDS and Flower, A and DeChaine, EG}, title = {Why georeferencing matters: Introducing a practical protocol to prepare species occurrence records for spatial analysis.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {765-777}, pmid = {29321912}, issn = {2045-7758}, abstract = {Species Distribution Models (SDMs) are widely used to understand environmental controls on species' ranges and to forecast species range shifts in response to climatic changes. The quality of input data is crucial determinant of the model's accuracy. While museum records can be useful sources of presence data for many species, they do not always include accurate geographic coordinates. Therefore, actual locations must be verified through the process of georeferencing. We present a practical, standardized manual georeferencing method (the Spatial Analysis Georeferencing Accuracy (SAGA) protocol) to classify the spatial resolution of museum records specifically for building improved SDMs. We used the high-elevation plant Saxifraga austromontana Wiegand (Saxifragaceae) as a case study to test the effect of using this protocol when developing an SDM. In MAXENT, we generated and compared SDMs using a comprehensive occurrence dataset that had undergone three different levels of georeferencing: (1) trained using all publicly available herbarium records of the species, minus outliers (2) trained using herbarium records claimed to be previously georeferenced, and (3) trained using herbarium records that we have manually georeferenced to a ≤ 1-km resolution using the SAGA protocol. Model predictions of suitable habitat for S. austromontana differed greatly depending on georeferencing level. The SDMs fitted with presence locations georeferenced using SAGA outperformed all others. Differences among models were exacerbated for future distribution predictions. Under rapid climate change, accurately forecasting the response of species becomes increasingly important. Failure to georeference location data and cull inaccurate samples leads to erroneous model output, limiting the utility of spatial analyses. We present a simple, standardized georeferencing method to be adopted by curators, ecologists, and modelers to improve the geographic accuracy of museum records and SDM predictions.}, } @article {pmid29321911, year = {2018}, author = {Holm, AK and Elameen, A and Oliver, BW and Brandsæter, LO and Fløistad, IS and Brurberg, MB}, title = {Low genetic variation of invasive Fallopia spp. in their northernmost European distribution range.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {755-764}, pmid = {29321911}, issn = {2045-7758}, abstract = {Knowledge about the reproduction strategies of invasive species is fundamental for effective control. The invasive Fallopia taxa (Japanese knotweed s.l.) reproduce mainly clonally in Europe, and preventing spread of vegetative fragments is the most important control measure. However, high levels of genetic variation within the hybrid F. × bohemica indicate that hybridization and seed dispersal could be important. In Norway in northern Europe, it is assumed that these taxa do not reproduce sexually due to low temperatures in the autumn when the plants are flowering. The main objective of this study was to examine the genetic variation of invasive Fallopia taxa in selected areas in Norway in order to evaluate whether the taxa may reproduce by seeds in their most northerly distribution range in Europe. Fallopia stands from different localities in Norway were analyzed with respect to prevalence of taxa, and genetic variation within and between taxa was studied using amplified fragment length polymorphism (AFLP). Taxonomic identification based on morphology corresponded with identification based on simple sequence repeats (SSR) and DNA ploidy levels (8× F. japonica, 6× F. × bohemica and 4× F. sachalinensis). No genetic variation within F. japonica was detected. All F. × bohemica samples belonged to a single AFLP genotype, but one sample had a different SSR genotype. Two SSR genotypes of F. sachalinensis were also detected. Extremely low genetic variation within the invasive Fallopia taxa indicates that these taxa do not reproduce sexually in the region, suggesting that control efforts can be focused on preventing clonal spread. Climate warming may increase sexual reproduction of invasive Fallopia taxa in northern regions. The hermaphrodite F. × bohemica is a potential pollen source for the male-sterile parental species. Targeted eradication of the hybrid can therefore reduce the risk of increased sexual reproduction under future warmer climate.}, } @article {pmid29321910, year = {2018}, author = {Chen, X and Tang, M and Zhang, X and Hamel, C and Li, W and Sheng, M}, title = {Why does oriental arborvitae grow better when mixed with black locust: Insight on nutrient cycling?.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {744-754}, pmid = {29321910}, issn = {2045-7758}, abstract = {To identify why tree growth differs by afforestation type is a matter of prime concern in forestry. A study was conducted to determine why oriental arborvitae (Platycladus orientalis) grows better in the presence of black locust (Robinia pseudoacacia) than in monoculture. Different types of stands (i.e., monocultures and mixture of black locust and oriental arborvitae, and native grassland as a control) were selected in the Loess Plateau, China. The height and diameter at breast height of each tree species were measured, and soil, shoot, and root samples were sampled. The arbuscular mycorrhizal (AM) attributes, shoot and root nutrient status, height and diameter of black locust were not influenced by the presence of oriental arborvitae. For oriental arborvitae, however, growing in mixture increased height and diameter and reduced shoot Mn, Ca, and Mg contents, AM fungal spore density, and colonization rate. Major changes in soil properties also occurred, primarily in soil water, NO 3-N, and available K levels and in soil enzyme activity. The increase in soil water, N, and K availability in the presence of black locust stimulated oriental arborvitae growth, and black locust in the mixed stand seems to suppress the development of AM symbiosis in oriental arborvitae roots, especially the production of AM fungal spores and vesicles, through improving soil water and N levels, thus freeing up carbon to fuel plant growth. Overall, the presence of black locust favored oriental arborvitae growth directly by improving soil water and fertility and indirectly by repressing AM symbiosis in oriental arborvitae roots.}, } @article {pmid29321909, year = {2018}, author = {Ramsey, DSL and Barclay, C and Campbell, CD and Dewar, E and MacDonald, AJ and Modave, E and Quasim, S and Sarre, SD}, title = {Detecting rare carnivores using scats: Implications for monitoring a fox incursion into Tasmania.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {732-743}, pmid = {29321909}, issn = {2045-7758}, abstract = {The ability to detect the incursion of an invasive species or destroy the last individuals during an eradication program are some of the most difficult aspects of invasive species management. The presence of foxes in Tasmania is a contentious issue with recent structured monitoring efforts, involving collection of carnivore scats and testing for fox DNA, failing to detect any evidence of foxes. Understanding the likelihood that monitoring efforts would detect fox presence, given at least one is present, is therefore critical for understanding the role of scat monitoring for informing the response to an incursion. We undertook trials to estimate the probability of fox scat detection through monitoring by scat-detector dogs and person searches and used this information to critically evaluate the power of scat monitoring efforts for detecting foxes in the Tasmanian landscape. The probability of detecting a single scat present in a 1-km2 survey unit was highest for scat-detector dogs searches (0.053) compared with person searches (x¯≅0.015) for each 10 km of search effort. Simulation of the power of recent scat monitoring efforts undertaken in Tasmania from 2011 to 2015 suggested that single foxes would have to be present in at least 20 different locations or fox breeding groups present in at least six different locations, in order to be detected with a high level of confidence (>0.80). We have shown that highly structured detection trials can provide managers with the quantitative tools needed to make judgments about the power of large-scale scat monitoring programs. Results suggest that a fox population, if present in Tasmania, could remain undetected by a large-scale, structured scat monitoring program. Therefore, it is likely that other forms of surveillance, in conjunction with scat monitoring, will be necessary to demonstrate that foxes are absent from Tasmania with high confidence.}, } @article {pmid29321908, year = {2018}, author = {Nwankwo, EC and Pallari, CT and Hadjioannou, L and Ioannou, A and Mulwa, RK and Kirschel, ANG}, title = {Rapid song divergence leads to discordance between genetic distance and phenotypic characters important in reproductive isolation.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {716-731}, pmid = {29321908}, issn = {2045-7758}, abstract = {The criteria for species delimitation in birds have long been debated, and several recent studies have proposed new methods for such delimitation. On one side, there is a large consensus of investigators who believe that the only evidence that can be used to delimit species is molecular phylogenetics, and with increasing numbers of markers to gain better support, whereas on the other, there are investigators adopting alternative approaches based largely on phenotypic differences, including in morphology and communication signals. Yet, these methods have little to say about rapid differentiation in specific traits shown to be important in reproductive isolation. Here, we examine variation in phenotypic (morphology, plumage, and song) and genotypic (mitochondrial and nuclear DNA) traits among populations of yellow-rumped tinkerbird Pogoniulus bilineatus in East Africa. Strikingly, song divergence between the P. b. fischeri subspecies from Kenya and Zanzibar and P. b. bilineatus from Tanzania is discordant with genetic distance, having occurred over a short time frame, and playback experiments show that adjacent populations of P. b. bilineatus and P. b. fischeri do not recognize one another's songs. While such rapid divergence might suggest a founder effect following invasion of Zanzibar, molecular evidence suggests otherwise, with insular P. b. fischeri nested within mainland P. b. fischeri. Populations from the Eastern Arc Mountains are genetically more distant, yet share the same song with P. b. bilineatus from Coastal Tanzania and Southern Africa, suggesting they would interbreed. We believe investigators ought to examine potentially rapid divergence in traits important in species recognition and sexual selection when delimiting species, rather than relying entirely on arbitrary quantitative characters or molecular markers.}, } @article {pmid29321907, year = {2018}, author = {Lortie, CJ and Gruber, E and Filazzola, A and Noble, T and Westphal, M}, title = {The Groot Effect: Plant facilitation and desert shrub regrowth following extensive damage.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {706-715}, pmid = {29321907}, issn = {2045-7758}, abstract = {Deserts are increasing in extent globally, but existing deserts are decreasing in health. The basic biology and ecology of foundation plant species in deserts are limited. This is a direct study that provides an estimate of the capacity for a locally dominant foundation shrub species in California to recover from damage. Desert shrubs are cleared and damaged by humans for many purposes including agriculture, oil and gas production, and sustainable energy developments; we need to know whether foundation species consistently facilitate the abundance and diversity of other plants in high-stress ecosystems and whether they can recover. A total of 20 Ephedra californica shrubs were clipped to the ground at a single site and systematically resampled for regrowth 2 years later. These shrubs were damaged once and regrew rapidly, and relatively, larger shrubs were not more resilient. This study provides evidence for what we termed the "Groot Effect" because smaller individuals of this shrub species can recover from significant aboveground damage and continue to have positive effects on other plant species (similar to the popular culture reference to a benefactor tree species). The density of other plant species was consistently facilitated while effects on diversity varied with season. These findings confirm that E. californica is a foundation species that can be an important restoration tool within the deserts of California in spite of extreme cycles of drought and physical damage to its canopy.}, } @article {pmid29321906, year = {2018}, author = {Capp, E and Liebl, AL and Cones, AG and Russell, AF}, title = {Advancing breeding phenology does not affect incubation schedules in chestnut-crowned babblers: Opposing effects of temperature and wind.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {696-705}, pmid = {29321906}, issn = {2045-7758}, abstract = {Projecting population responses to climate change requires an understanding of climatic impacts on key components of reproduction. Here, we investigate the associations among breeding phenology, climate and incubation schedules in the chestnut-crowned babbler (Pomatostomus ruficeps), a 50 g passerine with female-only, intermittent incubation that typically breeds from late winter (July) to early summer (November). During daylight hours, breeding females spent an average of 33 min on the nest incubating (hereafter on-bouts) followed by 24-min foraging (hereafter off-bouts), leading to an average daytime nest attentiveness of 60%. Nest attentiveness was 25% shorter than expected from allometric calculations, largely because off-bout durations were double the expected value for a species with 16 g clutches (4 eggs × 4 g/egg). On-bout durations and daily attentiveness were both negatively related to ambient temperature, presumably because increasing temperatures allowed more time to be allocated to foraging with reduced detriment to egg cooling. By contrast, on-bout durations were positively associated with wind speed, in this case because increasing wind speed exacerbated egg cooling during off-bouts. Despite an average temperature change of 12°C across the breeding season, breeding phenology had no effect on incubation schedules. This surprising result arose because of a positive relationship between temperature and wind speed across the breeding season: Any benefit of increasing temperatures was canceled by apparently detrimental consequences of increasing wind speed on egg cooling. Our results indicate that a greater appreciation for the associations among climatic variables and their independent effects on reproductive investment are necessary to understand the effects of changing climates on breeding phenology.}, } @article {pmid29321905, year = {2018}, author = {Williams, KE and Huyvaert, KP and Vercauteren, KC and Davis, AJ and Piaggio, AJ}, title = {Detection and persistence of environmental DNA from an invasive, terrestrial mammal.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {688-695}, pmid = {29321905}, issn = {2045-7758}, abstract = {Invasive Sus scrofa, a species commonly referred to as wild pig or feral swine, is a destructive invasive species with a rapidly expanding distribution across the United States. We used artificial wallows and small waterers to determine the minimum amount of time needed for pig eDNA to accumulate in the water source to a detectable level. We removed water from the artificial wallows and tested eDNA detection over the course of 2 weeks to understand eDNA persistence. We show that our method is sensitive enough to detect very low quantities of eDNA shed by a terrestrial mammal that has limited interaction with water. Our experiments suggest that the number of individuals shedding into a water system can affect persistence of eDNA. Use of an eDNA detection technique can benefit management efforts by providing a sensitive method for finding even small numbers of individuals that may be elusive using other methods.}, } @article {pmid29321904, year = {2018}, author = {Ankutowicz, EJ and Laird, RA}, title = {Offspring of older parents are smaller-but no less bilaterally symmetrical-than offspring of younger parents in the aquatic plant Lemna turionifera.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {679-687}, pmid = {29321904}, issn = {2045-7758}, abstract = {Offspring quality decreases with parental age in many taxa, with offspring of older parents exhibiting reduced life span, reproductive capacity, and fitness, compared to offspring of younger parents. These "parental age effects," whose consequences arise in the next generation, can be considered as manifestations of parental senescence, in addition to the more familiar age-related declines in parent-generation survival and reproduction. Parental age effects are important because they may have feedback effects on the evolution of demographic trajectories and longevity. In addition to altering the timing of offspring life-history milestones, parental age effects can also have a negative impact on offspring size, with offspring of older parents being smaller than offspring of younger parents. Here, we consider the effects of advancing parental age on a different aspect of offspring morphology, body symmetry. In this study, we followed all 403 offspring of 30 parents of a bilaterally symmetrical, clonally reproducing aquatic plant species, Lemna turionifera, to test the hypothesis that successive offspring become less symmetrical as their parent ages, using the "Continuous Symmetry Measure" as an index. Although successive offspring of aging parents older than one week became smaller and smaller, we found scant evidence for any reduction in bilateral symmetry.}, } @article {pmid29321903, year = {2018}, author = {Li, H and Kalcounis-Rueppell, M}, title = {Separating the effects of water quality and urbanization on temperate insectivorous bats at the landscape scale.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {667-678}, pmid = {29321903}, issn = {2045-7758}, abstract = {Many local scale studies have shown that bats respond to water quality degradation or urbanization in a species-specific manner. However, few have separated the effects of urbanization versus water quality degradation on bats, in single city or single watershed case studies. Across North Carolina, USA, we used the standardized North American Bat Monitoring Program mobile transect protocol to survey bat activity in 2015 and 2016 at 41 sites. We collected statewide water quality and urban land cover data to disentangle the effects of urbanization and water quality degradation on bats at the landscape scale. We found that statewide, water quality degradation and urbanization were not correlated. We found that bats responded to water quality degradation and urbanization independently at the landscape scale. Eptesicus fuscus and Lasiurus cinereus negatively responded to water quality degradation. Lasiurus borealis and Perimyotis subflavus positively responded to water quality degradation. Lasionycteris noctivagans did not respond to water quality degradation but was more active in more urbanized areas. Tadarida brasiliensis positively responded to urbanization and was less active in areas with degraded water quality. We show that bat-water quality relationships found at the local scale are evident at a landscape scale. We confirm that bats are useful bioindicators for both urbanization and water quality degradation. We suggest that water quality can be used to predict the presence of bat species of conservation concern, such as P. subflavus, in areas where it has not been studied locally.}, } @article {pmid29321902, year = {2018}, author = {Wachowiak, W and Perry, A and Donnelly, K and Cavers, S}, title = {Early phenology and growth trait variation in closely related European pine species.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {655-666}, pmid = {29321902}, issn = {2045-7758}, abstract = {Closely related taxa occupying different environments are valuable systems for studying evolution. In this study, we examined differences in early phenology (bud set, bud burst) and early growth in a common garden trial of closely related pine species: Pinus sylvestris, P. mugo, and P. uncinata. Seeds for the trial were sourced from populations across the ranges of each species in Europe. Over first 4 years of development, clear differences were observed between species, while the most significant intraspecific differentiation was observed among plants from P. sylvestris populations from continental European locations. Trait differences within P. sylvestris were highly correlated with altitude and latitude of the site of origin. Meanwhile, P. mugo populations from the Carpathians had the earliest bud set and bud flush compared to other populations of the species. Overall, populations from the P. mugo complex from heterogeneous mountain environments and P. sylvestris from the Scottish Highlands showed the highest within-population variation for the focal traits. Although the three species have been shown to be genetically highly similar, this study reveals large differences in key adaptive traits both among and within species.}, } @article {pmid29321901, year = {2018}, author = {Lu, HL and Xu, CX and Jin, YT and Hero, JM and Du, WG}, title = {Proximate causes of altitudinal differences in body size in an agamid lizard.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {645-654}, pmid = {29321901}, issn = {2045-7758}, abstract = {Body size is directly linked to key life history traits such as growth, fecundity, and survivorship. Identifying the causes of body size variation is a critical task in ecological and evolutionary research. Body size variation along altitudinal gradients has received considerable attention; however, the underlying mechanisms are poorly understood. Here, we compared the growth rate and age structure of toad-headed lizards (Phrynocephalus vlangalii) from two populations found at different elevations in the Qinghai-Tibetan Plateau. We used mark-recapture and skeletochronological analysis to identify the potential proximate causes of altitudinal variation in body size. Lizards from the high-elevation site had higher growth rates and attained slightly larger adult body sizes than lizards from the low-elevation site. However, newborns produced by high-elevation females were smaller than those by low-elevation females. Von Bertalanffy growth estimates predicted high-elevation individuals would reach sexual maturity at an earlier age and have a lower mean age than low-elevation individuals. Relatively lower mean age for the high-elevation population was confirmed using the skeletochronological analysis. These results support the prediction that a larger adult body size of high-elevation P. vlangalii results from higher growth rates, associated with higher resource availability.}, } @article {pmid29321900, year = {2018}, author = {Rapson, GL}, title = {Changing methodology results in operational drift in the meaning of leaf area index, necessitating implementation of foliage layer index.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {638-644}, pmid = {29321900}, issn = {2045-7758}, abstract = {Leaf area index (LAI) was developed to describe the number of layers of foliage in a monoculture. Subsequent expansion into measurement by remote-sensing methods has resulted in misrepresentation of LAI. The new name foliage layer index (FLI) is applied to a more simply estimated version of Goodall's "cover repetition," that is, the number of layers of foliage a single species has, either within a community or in monoculture. The relationship of FLI with cover is demonstrated in model communities, and some potential relationships between FLI and species' habit are suggested. FLI comm is a new formulation for the number of layers of foliage in a mixed-species' community. LAI should now be reserved for remote-sensing applications in mixed communities, where it is probably a nonlinear measure of the density of light-absorbing pigments.}, } @article {pmid29321899, year = {2018}, author = {Yang, L and Li, P and Li, F and Ali, S and Sun, X and Hou, M}, title = {Silicon amendment to rice plants contributes to reduced feeding in a phloem-sucking insect through modulation of callose deposition.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {631-637}, pmid = {29321899}, issn = {2045-7758}, abstract = {Silicon (Si) uptake by Poaceae plants has beneficial effects on herbivore defense. Increased plant physical barrier and altered herbivorous feeding behaviors are documented to reduce herbivorous arthropod feeding and contribute to enhanced plant defense. Here, we show that Si amendment to rice (Oryza sativa) plants contributes to reduced feeding in a phloem feeder, the brown planthopper (Nilaparvata lugens, BPH), through modulation of callose deposition. We associated the temporal dynamics of BPH feeding with callose deposition on sieve plates and further with callose synthase and hydrolase gene expression in plants amended with Si. Biological assays revealed that BPH feeding was lower in Si-amended than in nonamended plants in the early stages post-BPH infestation. Histological observation showed that BPH infestation triggered fast and strong callose deposition in Si-amended plants compared with nonamended plants. Analysis using qRT-PCR revealed that expression of the callose synthase gene OsGSL1 was up-regulated more and that the callose hydrolase (β-1,3-glucanase) gene Gns5 was up-regulated less in Si-amended than in nonamended plants during the initial stages of BPH infestation. These dynamic expression levels of OsGSL1 and Gns5 in response to BPH infestation correspond to callose deposition patterns in Si-amended versus nonamended plants. It is demonstrated here that BPH infestation triggers differential gene expression associated with callose synthesis and hydrolysis in Si-amended and nonamended rice plants, which allows callose to be deposited more on sieve tubes and sieve tube occlusions to be maintained more thus contributing to reduced BPH feeding on Si-amended plants.}, } @article {pmid29321898, year = {2018}, author = {Wu, X and Tang, Y and Chen, Y and Wen, J and Xie, Y and Lu, S}, title = {Sap flow characteristics and responses to summer rainfall for Pinus tabulaeformis and Hippophae rhamnoides in the Loess hilly region of China.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {617-630}, pmid = {29321898}, issn = {2045-7758}, abstract = {As a major driving element of the structure and function of arid and semiarid ecosystems, rainfall is the essential factor limiting plant biological processes. To clarify the characteristics of transpiration and responses to summer rainfall, sap flow density (Fd) of Pinus tabulaeformis and Hippophae rhamnoides was monitored using thermal dissipation probes. In addition, midday leaf water potential (ψm) and leaf stomatal conductance (Gs) were also analyzed to determine water use strategies. The results indicated that the diurnal variation in the normalized Fd values exhibited a single-peak curve for P. tabulaeformis, while H. rhamnoides showed multiple peaks. The normalized Fd for P. tabulaeformis remained relatively stable regardless of rainfall events. However, there was also a significant increase in the normalized Fd for H. rhamnoides in response to rainfall in June and August (p < .05), although no significant differences were observed in July. The normalized Fd values for P. tabulaeformis and H. rhamnoides fitted well with the derived variable of transpiration, an integrated index calculated from the vapor pressure deficit and solar radiation (Rs), using an exponential saturation function. The differences in fitting coefficients suggested that H. rhamnoides showed more sensitivity to summer rainfall (p < .01) than P. tabulaeformis. Furthermore, during the study period, P. tabulaeformis reduced Gs as soil water decreased, maintaining a relatively constant ψm; while H. rhamnoides allowed large fluctuations in ψm to maintain Gs. Therefore, P. tabulaeformis and H. rhamnoides should be considered isohydric and anisohydric species, respectively. And more consideration should be taken for H. rhamnoides in the afforestation activities and the local plantation management under the context of the frequently seasonal drought in the loess hilly region.}, } @article {pmid29321897, year = {2018}, author = {Busch, V and Klaus, VH and Penone, C and Schäfer, D and Boch, S and Prati, D and Müller, J and Socher, SA and Niinemets, Ü and Peñuelas, J and Hölzel, N and Fischer, M and Kleinebecker, T}, title = {Nutrient stoichiometry and land use rather than species richness determine plant functional diversity.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {601-616}, pmid = {29321897}, issn = {2045-7758}, abstract = {Plant functional traits reflect individual and community ecological strategies. They allow the detection of directional changes in community dynamics and ecosystemic processes, being an additional tool to assess biodiversity than species richness. Analysis of functional patterns in plant communities provides mechanistic insight into biodiversity alterations due to anthropogenic activity. Although studies have consi-dered of either anthropogenic management or nutrient availability on functional traits in temperate grasslands, studies combining effects of both drivers are scarce. Here, we assessed the impacts of management intensity (fertilization, mowing, grazing), nutrient stoichiometry (C, N, P, K), and vegetation composition on community-weighted means (CWMs) and functional diversity (Rao's Q) from seven plant traits in 150 grasslands in three regions in Germany, using data of 6 years. Land use and nutrient stoichiometry accounted for larger proportions of model variance of CWM and Rao's Q than species richness and productivity. Grazing affected all analyzed trait groups; fertilization and mowing only impacted generative traits. Grazing was clearly associated with nutrient retention strategies, that is, investing in durable structures and production of fewer, less variable seed. Phenological variability was increased. Fertilization and mowing decreased seed number/mass variability, indicating competition-related effects. Impacts of nutrient stoichiometry on trait syndromes varied. Nutrient limitation (large N:P, C:N ratios) promoted species with conservative strategies, that is, investment in durable plant structures rather than fast growth, fewer seed, and delayed flowering onset. In contrast to seed mass, leaf-economics variability was reduced under P shortage. Species diversity was positively associated with the variability of generative traits. Synthesis. Here, land use, nutrient availability, species richness, and plant functional strategies have been shown to interact complexly, driving community composition, and vegetation responses to management intensity. We suggest that deeper understanding of underlying mechanisms shaping community assembly and biodiversity will require analyzing all these parameters.}, } @article {pmid29321896, year = {2018}, author = {Wódkiewicz, M and Chwedorzewska, KJ and Bednarek, PT and Znój, A and Androsiuk, P and Galera, H}, title = {How much of the invader's genetic variability can slip between our fingers? A case study of secondary dispersal of Poa annua on King George Island (Antarctica).}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {592-600}, pmid = {29321896}, issn = {2045-7758}, abstract = {We studied an invasion of Poa annua on King George Island (Maritime Antarctic). The remoteness of this location, its geographic isolation, and its limited human traffic provided an opportunity to trace the history of an invasion of the species. Poa annua was recorded for the first time at H. Arctowski Polish Antarctic Station in the austral summer of 1985/6. In 2008/9, the species was observed in a new locality at the Ecology Glacier Forefield (1.5 km from "Arctowski"). We used AFLP to analyze the genetic differences among three populations of P. annua: the two mentioned above (Station and Forefield) and the putative origin of the introduction, Warsaw (Poland). There was 38% genetic variance among the populations. Pairwise ФPT was 0.498 between the Forefield and Warsaw populations and 0.283 between Warsaw and Station. There were 15 unique bands in the Warsaw population (frequency from 6% to 100%) and one in the Station/Forefield populations (which appears in all analyzed individuals from both populations). The Δ(K) parameter indicated two groups of samples: Warsaw/Station and Forefield. As indicated by Fu's Fs statistics and an analysis of mismatch distribution, the Forefield population underwent a bottleneck and/or founder effect. The Forefield population was likely introduced by secondary dispersal from the Station population.}, } @article {pmid29321895, year = {2018}, author = {Jeffery, E and Córdoba-Aguilar, A and Roitberg, B}, title = {Impact of male alternative reproductive tactics on female costs of sexual conflict under variation in operational sex ratio and population density.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {584-591}, pmid = {29321895}, issn = {2045-7758}, abstract = {Sexual conflict over mating rate is both pervasive and evolutionarily costly. For females, the lifetime reproductive fitness costs that arise through interactions with potential mates will be influenced by the frequency of such interactions, and the fitness cost of each interaction. Both of these factors are likely to be influenced by variation in operational sex ratio (OSR) and population density. Variation in OSR- and density-dependent male alternative reproductive tactics (ARTs) may be particularly important if the fitness costs that females experience vary with the reproductive tactics that males express. Using a simple model, we consider several examples of OSR- and/or density-dependent variation in male ARTs and the frequency of male-female interactions, and find that variation in the expression of male ARTs has the potential to augment or diminish the costs of frequent male interactions for females. Accurately documenting variation in the expression of male ARTs and associated female fitness costs will benefit future work in this area.}, } @article {pmid29321894, year = {2018}, author = {Donaldson, ME and Rico, Y and Hueffer, K and Rando, HM and Kukekova, AV and Kyle, CJ}, title = {Development of a genotype-by-sequencing immunogenetic assay as exemplified by screening for variation in red fox with and without endemic rabies exposure.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {572-583}, pmid = {29321894}, issn = {2045-7758}, support = {R01 GM120782/GM/NIGMS NIH HHS/United States ; }, abstract = {Pathogens are recognized as major drivers of local adaptation in wildlife systems. By determining which gene variants are favored in local interactions among populations with and without disease, spatially explicit adaptive responses to pathogens can be elucidated. Much of our current understanding of host responses to disease comes from a small number of genes associated with an immune response. High-throughput sequencing (HTS) technologies, such as genotype-by-sequencing (GBS), facilitate expanded explorations of genomic variation among populations. Hybridization-based GBS techniques can be leveraged in systems not well characterized for specific variants associated with disease outcome to "capture" specific genes and regulatory regions known to influence expression and disease outcome. We developed a multiplexed, sequence capture assay for red foxes to simultaneously assess ~300-kbp of genomic sequence from 116 adaptive, intrinsic, and innate immunity genes of predicted adaptive significance and their putative upstream regulatory regions along with 23 neutral microsatellite regions to control for demographic effects. The assay was applied to 45 fox DNA samples from Alaska, where three arctic rabies strains are geographically restricted and endemic to coastal tundra regions, yet absent from the boreal interior. The assay provided 61.5% on-target enrichment with relatively even sequence coverage across all targeted loci and samples (mean = 50×), which allowed us to elucidate genetic variation across introns, exons, and potential regulatory regions (4,819 SNPs). Challenges remained in accurately describing microsatellite variation using this technique; however, longer-read HTS technologies should overcome these issues. We used these data to conduct preliminary analyses and detected genetic structure in a subset of red fox immune-related genes between regions with and without endemic arctic rabies. This assay provides a template to assess immunogenetic variation in wildlife disease systems.}, } @article {pmid29321893, year = {2018}, author = {Godfrey, RK and Yerger, EH and Nuttle, TJ}, title = {Opposing deer and caterpillar foraging preferences may prevent reductions in songbird prey biomass in historically overbrowsed forests.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {560-571}, pmid = {29321893}, issn = {2045-7758}, abstract = {Overbrowsing by ungulates decimates plant populations and reduces diversity in a variety of ecosystems, but the mechanisms by which changes to plant community composition influence other trophic levels are poorly understood. In addition to removal of avian nesting habitat, browsing is hypothesized to reduce bird density and diversity through reduction of insect prey on browse-tolerant hosts left behind by deer. In this study, we excluded birds from branches of six tree species to quantify differences in songbird prey removal across trees that vary in deer browse preference. Early in the breeding season, birds preyed on caterpillars at levels proportional to their abundance on each host. Combining these data with tree species composition data from stands exposed to experimentally controlled deer densities over 30 years ago, we tested whether overbrowsing by white-tailed deer reduces prey biomass long after deer densities are reduced. Our analysis predicts total prey availability in the canopy of regenerating forests is fairly robust to historic exposure to high deer densities, though distribution of prey available from host species changes dramatically. This predicted compensatory effect was unexpected and is driven by high prey abundance on a single host tree species avoided by browsing deer, Prunus serotina. Thus, while we confirm that prey abundance on host trees can act as a reliable predictor for relative prey availability, this study shows that quantifying prey abundance across host trees is essential to understanding how changes in tree species composition interact with ungulate browse preference to determine prey availability for songbirds.}, } @article {pmid29321892, year = {2018}, author = {Morin, RS and Gottschalk, KW and Ostry, ME and Liebhold, AM}, title = {Regional patterns of declining butternut (Juglans cinerea L.) suggest site characteristics for restoration.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {546-559}, pmid = {29321892}, issn = {2045-7758}, abstract = {Butternut trees dying from a canker disease were first reported in southwestern Wisconsin in 1967. Since then, the disease has caused extensive mortality of butternut throughout its North American range. The objectives of this study were to quantify changes in butternut populations and density across its range and identify habitat characteristics of sites where butternut is surviving in order to locate regions for potential butternut restoration. The natural range of butternut (Juglans cinerea L.) extends over a large region of eastern N. America encompassing New Brunswick south to North Carolina, north to Minnesota, and southwest to Missouri. Despite the species' large range, it is typically not a common tree, comprising a relatively minor component of several different forest types. We evaluated change in butternut abundance and volume from current and historic data from 21 states in the eastern United States. We related abundance and volume at two time periods to a suite of ecological and site factors in order to characterize site conditions where butternut survived. We also assessed the current level of butternut mortality across its range. Since the 1980s, the number of butternut trees and butternut volume have decreased by 58% and 44%, respectively, across its US range. Substantial relative decreases in tree numbers and volume occurred in most ecoregion sections. Five environmental variables were found to be significant predictors of butternut presence. The potential impacts of butternut canker are particularly acute as the canker pathogen invasion pushes a rare tree species toward extinction, at least at a local scale. Based on the results presented here, large-diameter maple/beech/birch stands in dry, upland sites in eastern Minnesota, western Wisconsin, and upstate New York appear to offer the most favorable conditions for butternut growth and survival and thus may be the best stands for planting resistant butternut trees.}, } @article {pmid29321891, year = {2018}, author = {Hartvig, I and So, T and Changtragoon, S and Tran, HT and Bouamanivong, S and Theilade, I and Kjær, ED and Nielsen, LR}, title = {Population genetic structure of the endemic rosewoods Dalbergia cochinchinensis and D. oliveri at a regional scale reflects the Indochinese landscape and life-history traits.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {530-545}, pmid = {29321891}, issn = {2045-7758}, abstract = {Indochina is a biodiversity hot spot and harbors a high number of endemic species, most of which are poorly studied. This study explores the genetic structure and reproductive system of the threatened endemic timber species Dalbergia cochinchinensis and Dalbergia oliveri using microsatellite data from populations across Indochina and relates it to landscape characteristics and life-history traits. We found that the major water bodies in the region, Mekong and Tonle Sap, represented barriers to gene flow and that higher levels of genetic diversity were found in populations in the center of the distribution area, particularly in Cambodia. We suggest that this pattern is ancient, reflecting the demographic history of the species and possible location of refugia during earlier time periods with limited forest cover, which was supported by signs of old genetic bottlenecks. The D. oliveri populations had generally high levels of genetic diversity (mean He = 0.73), but also strong genetic differentiation among populations (global GST = 0.13), while D. cochinchinensis had a moderate level of genetic diversity (mean He = 0.55), and an even stronger level of differentiation (global GST = 0.25). These differences in genetic structure can be accounted for by a higher level of gene flow in D. oliveri due to a higher dispersal capacity, but also by the broader distribution area for D. oliveri, and the pioneer characteristics of D. cochinchinensis. This study represents the first detailed analysis of landscape genetics for tree species in Indochina, and the found patterns might be common for other species with similar ecology.}, } @article {pmid29321890, year = {2018}, author = {Horreo, JL and Valiente, AG and Ardura, A and Blanco, A and Garcia-Gonzalez, C and Garcia-Vazquez, E}, title = {Nature versus nurture? Consequences of short captivity in early stages.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {521-529}, pmid = {29321890}, issn = {2045-7758}, abstract = {Biological changes occurring as a consequence of domestication and/or captivity are not still deeply known. In Atlantic salmon (Salmo salar), endangered (Southern Europe) populations are enhanced by supportive breeding, which involves only 6 months of captive rearing following artificial spawning of wild-collected adults. In this work, we assess whether several fitness-correlated life-history traits (migratory behavior, straying rate, age at maturity, and growth) are affected by early exposure to the captive environment within a generation, before reproduction thus before genetic selection. Results showed significant differences in growth and migratory behavior (including straying), associated with this very short period of captivity in natural fish populations, changing even genetic variability (decreased in hatchery-reared adults) and the native population structure within and between rivers of the species. These changes appeared within a single generation, suggesting very short time of captivity is enough for initiating changes normally attributed to domestication. These results may have potential implications for the long-term population stability/viability of species subjected to restoration and enhancement processes and could be also considered for the management of zoo populations.}, } @article {pmid29321889, year = {2018}, author = {Walsh, DP and Norton, AS and Storm, DJ and Van Deelen, TR and Heisey, DM}, title = {Using expert knowledge to incorporate uncertainty in cause-of-death assignments for modeling of cause-specific mortality.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {509-520}, pmid = {29321889}, issn = {2045-7758}, abstract = {Implicit and explicit use of expert knowledge to inform ecological analyses is becoming increasingly common because it often represents the sole source of information in many circumstances. Thus, there is a need to develop statistical methods that explicitly incorporate expert knowledge, and can successfully leverage this information while properly accounting for associated uncertainty during analysis. Studies of cause-specific mortality provide an example of implicit use of expert knowledge when causes-of-death are uncertain and assigned based on the observer's knowledge of the most likely cause. To explicitly incorporate this use of expert knowledge and the associated uncertainty, we developed a statistical model for estimating cause-specific mortality using a data augmentation approach within a Bayesian hierarchical framework. Specifically, for each mortality event, we elicited the observer's belief of cause-of-death by having them specify the probability that the death was due to each potential cause. These probabilities were then used as prior predictive values within our framework. This hierarchical framework permitted a simple and rigorous estimation method that was easily modified to include covariate effects and regularizing terms. Although applied to survival analysis, this method can be extended to any event-time analysis with multiple event types, for which there is uncertainty regarding the true outcome. We conducted simulations to determine how our framework compared to traditional approaches that use expert knowledge implicitly and assume that cause-of-death is specified accurately. Simulation results supported the inclusion of observer uncertainty in cause-of-death assignment in modeling of cause-specific mortality to improve model performance and inference. Finally, we applied the statistical model we developed and a traditional method to cause-specific survival data for white-tailed deer, and compared results. We demonstrate that model selection results changed between the two approaches, and incorporating observer knowledge in cause-of-death increased the variability associated with parameter estimates when compared to the traditional approach. These differences between the two approaches can impact reported results, and therefore, it is critical to explicitly incorporate expert knowledge in statistical methods to ensure rigorous inference.}, } @article {pmid29321888, year = {2018}, author = {Sample, C and Fryxell, JM and Bieri, JA and Federico, P and Earl, JE and Wiederholt, R and Mattsson, BJ and Flockhart, DTT and Nicol, S and Diffendorfer, JE and Thogmartin, WE and Erickson, RA and Norris, DR}, title = {A general modeling framework for describing spatially structured population dynamics.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {493-508}, pmid = {29321888}, issn = {2045-7758}, abstract = {Variation in movement across time and space fundamentally shapes the abundance and distribution of populations. Although a variety of approaches model structured population dynamics, they are limited to specific types of spatially structured populations and lack a unifying framework. Here, we propose a unified network-based framework sufficiently novel in its flexibility to capture a wide variety of spatiotemporal processes including metapopulations and a range of migratory patterns. It can accommodate different kinds of age structures, forms of population growth, dispersal, nomadism and migration, and alternative life-history strategies. Our objective was to link three general elements common to all spatially structured populations (space, time and movement) under a single mathematical framework. To do this, we adopt a network modeling approach. The spatial structure of a population is represented by a weighted and directed network. Each node and each edge has a set of attributes which vary through time. The dynamics of our network-based population is modeled with discrete time steps. Using both theoretical and real-world examples, we show how common elements recur across species with disparate movement strategies and how they can be combined under a unified mathematical framework. We illustrate how metapopulations, various migratory patterns, and nomadism can be represented with this modeling approach. We also apply our network-based framework to four organisms spanning a wide range of life histories, movement patterns, and carrying capacities. General computer code to implement our framework is provided, which can be applied to almost any spatially structured population. This framework contributes to our theoretical understanding of population dynamics and has practical management applications, including understanding the impact of perturbations on population size, distribution, and movement patterns. By working within a common framework, there is less chance that comparative analyses are colored by model details rather than general principles.}, } @article {pmid29321887, year = {2018}, author = {Leclerc, JC and Viard, F}, title = {Habitat formation prevails over predation in influencing fouling communities.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {477-492}, pmid = {29321887}, issn = {2045-7758}, abstract = {Coastal human-made structures, such as marinas and harbors, are expanding worldwide. Species assemblages described from these artificial habitats are novel relative to natural reefs, particularly in terms of the abundance of nonindigenous species (NIS). Although these fouling assemblages are clearly distinctive, the ecosystem functioning and species interactions taking place there are little understood. For instance, large predators may influence the fouling community development either directly (feeding on sessile fauna) or indirectly (feeding on small predators associated with these assemblages). In addition, by providing refuges, habitat complexity may modify the outcome of species interactions and the extent of biotic resistance (e.g., by increasing the abundance of niche-specific competitors and predators of NIS). Using experimental settlement panels deployed in the field for 2.5 months, we tested the influence of predation (i.e., caging experiment), artificial structural complexity (i.e., mimics of turf-forming species), and their interactions (i.e., refuge effects) on the development of sessile and mobile fauna in two marinas. In addition, we tested the role of biotic complexity-arising from the habitat-forming species that grew on the panels during the trial-on the richness and abundance of mobile fauna. The effect of predation and artificial habitat complexity was negligible, regardless of assemblage status (i.e., native, cryptogenic, and nonindigenous). Conversely, habitat-forming species and associated epibionts, responsible for biotic complexity, had a significant effect on mobile invertebrates (richness, abundance, and community structure). In particular, the richness and abundance of mobile NIS were positively affected by biotic complexity, with site-dependent relationships. Altogether, our results indicate that biotic complexity prevails over artificial habitat complexity in determining the distribution of mobile species under low predation pressure. Facilitation of native and non-native species thus seems to act upon diversity and community development: This process deserves further consideration in models of biotic resistance to invasion in urban marine habitats.}, } @article {pmid29321886, year = {2018}, author = {Nygaard, PH and Strand, LT and Stuanes, AO}, title = {Gap formation and dynamics after long-term steady state in an old-growth Picea abies stand in Norway: Above- and belowground interactions.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {462-476}, pmid = {29321886}, issn = {2045-7758}, abstract = {Stand dynamics and the gap initiation prior to gap formation are not well-understood because of its long-term nature and the scarcity of late-successional stands. Reconstruction of such disturbance is normally based on historical records and dendroecological methods. We investigated gap initiation and formation at the fine-scale stand level in the old-growth reserve of Karlshaugen in Norway. Given its long-term conservation history, and thorough mapping in permanent marked plots with spatially referenced trees, it provides an opportunity to present stand development before, during, and after gap formation. Late-successional decline in biomass was recorded after more than 50 years of close to steady state. Gaps in the canopy were mainly created by large old trees that had been killed by spruce bark beetles. Snapping by wind was the main reason for treefall. Long-term dominance of Norway spruce excluded downy birch and Scots pine from the stand. Comparisons of the forest floor soil properties between the gap and nongap area showed significantly higher concentrations of plant available Ca within the gap area. Plant root simulator (PRS™) probes showed significantly higher supply rates for Ca and Mg, but significantly lower K for the gap compared to the nongap area. Soil water from the gap area had significantly higher C:N ratios compared to the nongap area. Fine-scale variation with increasing distance to logs indicated that CWD is important for leaking of DOC and Ca. Our long-term study from Karlshaugen documents gap dynamics after more than 50 years of steady state and a multiscale disturbance regime in an old-growth forest. The observed disturbance dynamic caused higher aboveground and belowground heterogeneity in plots, coarse woody debris, and nutrients. Our study of the nutrient levels of the forest floor suggest that natural gaps of old-growth forest provide a long-lasting biogeochemical feedback system particularly with respect to Ca and probably also N. Norway spruce trees near the gap edge responded with high plasticity to reduced competition, showing the importance of the edge zone as hot spots for establishing heterogeneity, but also the potential for carbon sequestration in old-growth forest.}, } @article {pmid29321885, year = {2018}, author = {Paterson, RRM and Lima, N}, title = {Climate change affecting oil palm agronomy, and oil palm cultivation increasing climate change, require amelioration.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {452-461}, pmid = {29321885}, issn = {2045-7758}, abstract = {Palm oil is used in various valued commodities and is a large global industry worth over US$ 50 billion annually. Oil palms (OP) are grown commercially in Indonesia and Malaysia and other countries within Latin America and Africa. The large-scale land-use change has high ecological, economic, and social impacts. Tropical countries in particular are affected negatively by climate change (CC) which also has a detrimental impact on OP agronomy, whereas the cultivation of OP increases CC. Amelioration of both is required. The reduced ability to grow OP will reduce CC, which may allow more cultivation tending to increase CC, in a decreasing cycle. OP could be increasingly grown in more suitable regions occurring under CC. Enhancing the soil fauna may compensate for the effect of CC on OP agriculture to some extent. The effect of OP cultivation on CC may be reduced by employing reduced emissions from deforestation and forest degradation plans, for example, by avoiding illegal fire land clearing. Other ameliorating methods are reported herein. More research is required involving good management practices that can offset the increases in CC by OP plantations. Overall, OP-growing countries should support the Paris convention on reducing CC as the most feasible scheme for reducing CC.}, } @article {pmid29321884, year = {2018}, author = {Jones, JC and Fruciano, C and Hildebrand, F and Al Toufalilia, H and Balfour, NJ and Bork, P and Engel, P and Ratnieks, FL and Hughes, WO}, title = {Gut microbiota composition is associated with environmental landscape in honey bees.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {441-451}, pmid = {29321884}, issn = {2045-7758}, abstract = {There is growing recognition that the gut microbial community regulates a wide variety of important functions in its animal hosts, including host health. However, the complex interactions between gut microbes and environment are still unclear. Honey bees are ecologically and economically important pollinators that host a core gut microbial community that is thought to be constant across populations. Here, we examined whether the composition of the gut microbial community of honey bees is affected by the environmental landscape the bees are exposed to. We placed honey bee colonies reared under identical conditions in two main landscape types for 6 weeks: either oilseed rape farmland or agricultural farmland distant to fields of flowering oilseed rape. The gut bacterial communities of adult bees from the colonies were then characterized and compared based on amplicon sequencing of the 16S rRNA gene. While previous studies have delineated a characteristic core set of bacteria inhabiting the honey bee gut, our results suggest that the broad environment that bees are exposed to has some influence on the relative abundance of some members of that microbial community. This includes known dominant taxa thought to have functions in nutrition and health. Our results provide evidence for an influence of landscape exposure on honey bee microbial community and highlight the potential effect of exposure to different environmental parameters, such as forage type and neonicotinoid pesticides, on key honey bee gut bacteria. This work emphasizes the complexity of the relationship between the host, its gut bacteria, and the environment and identifies target microbial taxa for functional analyses.}, } @article {pmid29321883, year = {2018}, author = {Ottaviani, G and Tsakalos, JL and Keppel, G and Mucina, L}, title = {Quantifying the effects of ecological constraints on trait expression using novel trait-gradient analysis parameters.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {435-440}, pmid = {29321883}, issn = {2045-7758}, abstract = {Complex processes related to biotic and abiotic forces can impose limitations to assembly and composition of plant communities. Quantifying the effects of these constraints on plant functional traits across environmental gradients, and among communities, remains challenging. We define ecological constraint (Ci) as the combined, limiting effect of biotic interactions and environmental filtering on trait expression (i.e., the mean value and range of functional traits). Here, we propose a set of novel parameters to quantify this constraint by extending the trait-gradient analysis (TGA) methodology. The key parameter is ecological constraint, which is dimensionless and can be measured at various scales, for example, on population and community levels. It facilitates comparing the effects of ecological constraints on trait expressions across environmental gradients, as well as within and among communities. We illustrate the implementation of the proposed parameters using the bark thickness of 14 woody species along an aridity gradient on granite outcrops in southwestern Australia. We found a positive correlation between increasing environmental stress and strength of ecological constraint on bark thickness expression. Also, plants from more stressful habitats (shrublands on shallow soils and in sun-exposed locations) displayed higher ecological constraint for bark thickness than plants in more benign habitats (woodlands on deep soils and in sheltered locations). The relative ease of calculation and dimensionless nature of Ci allow it to be readily implemented at various scales and make it widely applicable. It therefore has the potential to advance the mechanistic understanding of the ecological processes shaping trait expression. Some future applications of the new parameters could be investigating the patterns of ecological constraints (1) among communities from different regions, (2) on different traits across similar environmental gradients, and (3) for the same trait across different gradient types.}, } @article {pmid29321882, year = {2018}, author = {Montagnani, L and Zanotelli, D and Tagliavini, M and Tomelleri, E}, title = {Timescale effects on the environmental control of carbon and water fluxes of an apple orchard.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {416-434}, pmid = {29321882}, issn = {2045-7758}, abstract = {Model parameterization and validation of earth-atmosphere interactions are generally performed using a single timescale (e.g., nearly instantaneous, daily, and annual), although both delayed responses and hysteretic effects have been widely recognized. The lack of consideration of these effects hampers our capability to represent them in empirical- or process-based models. Here we explore, using an apple orchard ecosystem in the North of Italy as a simplified case study, how the considered timescale impacts the relative importance of the single environmental variables in explaining observed net ecosystem exchange (NEE) and evapotranspiration (ET). Using 6 years of eddy covariance and meteorological information as input data, we found a decay of the relative importance of the modeling capability of photosynthetically active radiation in explaining both NEE and ET moving from half-hourly to seasonal timescale and an increase in the relative importance of air temperature (T) and VPD. Satellite NDVI, used as proxy of leaf development, added little improvement to overall modeling capability. Increasing the timescale, the number of variables needed for parameterization decreased (from 5 to 1), while the proportion of variance explained by the model increased (r2 from 0.56-0.78 to 0.85-0.90 for NEE and ET respectively). The wavelet coherence and the phase analyses showed that the two variables that increased their relative importance when the scale increased (T, VPD) were not in phase at the correlation peak of both ET and NEE. This phase shift in the time domain corresponds to a hysteretic response in the meteorological variables domain. This work confirms that the model parameterization should be performed using parameters calculated at the appropriate scale. It suggests that in managed ecosystems, where the interannual variability is minimized by the agronomic practices, the use of timescales large enough to include hysteretic and delayed responses reduces the number of required input variables and improves their explanatory capacity.}, } @article {pmid29321881, year = {2018}, author = {Bevilacqua, S and Ugland, KI and Plicanti, A and Scuderi, D and Terlizzi, A}, title = {An approach based on the total-species accumulation curve and higher taxon richness to estimate realistic upper limits in regional species richness.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {405-415}, pmid = {29321881}, issn = {2045-7758}, abstract = {Most of accumulation curves tend to underestimate species richness, as they do not consider spatial heterogeneity in species distribution, or are structured to provide lower bound estimates and limited extrapolations. The total-species (T-S) curve allows extrapolations over large areas while taking into account spatial heterogeneity, making this estimator more prone to attempt upper bound estimates of regional species richness. However, the T-S curve may overestimate species richness due to (1) the mismatch among the spatial units used in the accumulation model and the actual units of variation in β-diversity across the region, (2) small-scale patchiness, and/or (3) patterns of rarity of species. We propose a new framework allowing the T-S curve to limit overestimation and give an application to a large dataset of marine mollusks spanning over 11 km2 of subtidal bottom (W Mediterranean). As accumulation patterns are closely related across the taxonomic hierarchy up to family level, improvements of the T-S curve leading to more realistic estimates of family richness, that is, not exceeding the maximum number of known families potentially present in the area, can be considered as conducive to more realistic estimates of species richness. Results on real data showed that improvements of the T-S curve to accounts for true variations in β-diversity within the sampled areas, small-scale patchiness, and rarity of families led to the most plausible richness when all aspects were considered in the model. Data on simulated communities indicated that in the presence of high heterogeneity, and when the proportion of rare species was not excessive (>2/3), the procedure led to almost unbiased estimates. Our findings highlighted the central role of variations in β-diversity within the region when attempting to estimate species richness, providing a general framework exploiting the properties of the T-S curve and known family richness to estimate plausible upper bounds in γ-diversity.}, } @article {pmid29321880, year = {2018}, author = {Pedersen, SA and Hanssen, AE}, title = {Ocean acidification ameliorates harmful effects of warming in primary consumer.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {396-404}, pmid = {29321880}, issn = {2045-7758}, abstract = {Climate change-induced warming and ocean acidification are considered two imminent threats to marine biodiversity and current ecosystem structures. Here, we have for the first time examined an animal's response to a complete life cycle of exposure to co-occurring warming (+3°C) and ocean acidification (+1,600 μatm CO 2), using the key subarctic planktonic copepod, Calanus finmarchicus, as a model species. The animals were generally negatively affected by warming, which significantly reduced the females' energy status and reproductive parameters (respectively, 95% and 69%-87% vs. control). Unexpectedly, simultaneous acidification partially offset the negative effect of warming in an antagonistic manner, significantly improving reproductive parameters and hatching success (233%-340% improvement vs. single warming exposure). The results provide proof of concept that ocean acidification may partially offset negative effects caused by warming in some species. Possible explanations and ecological implications for the observed antagonistic effect are discussed.}, } @article {pmid29321879, year = {2018}, author = {Kermish-Wells, J and Massolo, A and Stenhouse, GB and Larsen, TA and Musiani, M}, title = {Space-time clusters for early detection of grizzly bear predation.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {382-395}, pmid = {29321879}, issn = {2045-7758}, abstract = {Accurate detection and classification of predation events is important to determine predation and consumption rates by predators. However, obtaining this information for large predators is constrained by the speed at which carcasses disappear and the cost of field data collection. To accurately detect predation events, researchers have used GPS collar technology combined with targeted site visits. However, kill sites are often investigated well after the predation event due to limited data retrieval options on GPS collars (VHF or UHF downloading) and to ensure crew safety when working with large predators. This can lead to missing information from small-prey (including young ungulates) kill sites due to scavenging and general site deterioration (e.g., vegetation growth). We used a space-time permutation scan statistic (STPSS) clustering method (SaTScan) to detect predation events of grizzly bears (Ursus arctos) fitted with satellite transmitting GPS collars. We used generalized linear mixed models to verify predation events and the size of carcasses using spatiotemporal characteristics as predictors. STPSS uses a probability model to compare expected cluster size (space and time) with the observed size. We applied this method retrospectively to data from 2006 to 2007 to compare our method to random GPS site selection. In 2013-2014, we applied our detection method to visit sites one week after their occupation. Both datasets were collected in the same study area. Our approach detected 23 of 27 predation sites verified by visiting 464 random grizzly bear locations in 2006-2007, 187 of which were within space-time clusters and 277 outside. Predation site detection increased by 2.75 times (54 predation events of 335 visited clusters) using 2013-2014 data. Our GLMMs showed that cluster size and duration predicted predation events and carcass size with high sensitivity (0.72 and 0.94, respectively). Coupling GPS satellite technology with clusters using a program based on space-time probability models allows for prompt visits to predation sites. This enables accurate identification of the carcass size and increases fieldwork efficiency in predation studies.}, } @article {pmid29321878, year = {2018}, author = {Dobeš, C and Scheffknecht, S and Fenko, Y and Prohaska, D and Sykora, C and Hülber, K}, title = {Asymmetric reproductive interference: The consequences of cross-pollination on reproductive success in sexual-apomictic populations of Potentilla puberula (Rosaceae).}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {365-381}, pmid = {29321878}, issn = {2045-7758}, abstract = {Apomixis evolves from a sexual background and usually is linked to polyploidization. Pseudogamous gametophytic apomicts, which require a fertilization to initiate seed development, of various ploidy levels frequently co-occur with their lower-ploid sexual ancestors, but the stability of such mixed populations is affected by reproductive interferences mediated by cross-pollination. Thereby, reproductive success of crosses depends on the difference in ploidy levels of mating partners, that is, on tolerance of deviation from the balanced ratio of maternal versus paternal genomes. Quality of pollen can further affect reproductive success in intercytotype pollinations. Cross-fertilization, however, can be avoided by selfing which may be induced upon pollination with mixtures of self- and cross-pollen (i.e., mentor effects). We tested for reproductive compatibility of naturally co-occurring tetraploid sexuals and penta- to octoploid apomicts in the rosaceous species Potentilla puberula by means of controlled crosses. We estimated the role of selfing as a crossing barrier and effects of self- and cross-pollen quality as well as maternal: paternal genomic ratios in the endosperm on reproductive success. Cross-fertilization of sexuals by apomicts was not blocked by selfing, and seed set was reduced in hetero- compared to homoploid crosses. Thereby, seed set was negatively related to deviations from balanced parental genomic ratios in the endosperm. In contrast, seed set in the apomictic cytotypes was not reduced in hetero- compared to homoploid crosses. Thus, apomictic cytotypes either avoided intercytotype cross-fertilization through selfing, tolerated intercytotype cross-fertilizations without negative effects on reproductive success, or even benefitted from higher pollen quality in intercytotype pollinations. Our experiment provides evidence for asymmetric reproductive interference, in favor of the apomicts, with significantly reduced seed set of sexuals in cytologically mixed populations, whereas seed set in apomicts was not affected. Incompleteness of crossing barriers further indicated at least partial losses of a parental genomic endosperm balance requirement.}, } @article {pmid29321877, year = {2018}, author = {Smith, JT and Tack, JD and Doherty, KE and Allred, BW and Maestas, JD and Berkeley, LI and Dettenmaier, SJ and Messmer, TA and Naugle, DE}, title = {Phenology largely explains taller grass at successful nests in greater sage-grouse.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {356-364}, pmid = {29321877}, issn = {2045-7758}, abstract = {Much interest lies in the identification of manageable habitat variables that affect key vital rates for species of concern. For ground-nesting birds, vegetation surrounding the nest may play an important role in mediating nest success by providing concealment from predators. Height of grasses surrounding the nest is thought to be a driver of nest survival in greater sage-grouse (Centrocercus urophasianus; sage-grouse), a species that has experienced widespread population declines throughout their range. However, a growing body of the literature has found that widely used field methods can produce misleading inference on the relationship between grass height and nest success. Specifically, it has been demonstrated that measuring concealment following nest fate (failure or hatch) introduces a temporal bias whereby successful nests are measured later in the season, on average, than failed nests. This sampling bias can produce inference suggesting a positive effect of grass height on nest survival, though the relationship arises due to the confounding effect of plant phenology, not an effect on predation risk. To test the generality of this finding for sage-grouse, we reanalyzed existing datasets comprising >800 sage-grouse nests from three independent studies across the range where there was a positive relationship found between grass height and nest survival, including two using methods now known to be biased. Correcting for phenology produced equivocal relationships between grass height and sage-grouse nest survival. Viewed in total, evidence for a ubiquitous biological effect of grass height on sage-grouse nest success across time and space is lacking. In light of these findings, a reevaluation of land management guidelines emphasizing specific grass height targets to promote nest success may be merited.}, } @article {pmid29321876, year = {2018}, author = {Cory, AL and Schneider, JM}, title = {Effects of social information on life history and mating tactics of males in the orb-web spider Argiope bruennichi.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {344-355}, pmid = {29321876}, issn = {2045-7758}, abstract = {Informed mating decisions are often based on social cues providing information about prospective mating opportunities. Social information early in life can trigger developmental modifications and influence later mating decisions. A high adaptive value of such adjustments is particularly obvious in systems where potential mating rates are extremely limited and have to be carried out in a short time window. Males of the sexually cannibalistic spider Argiope bruennichi can achieve maximally two copulations which they can use for one (monogyny) or two females (bigyny). The choice between these male mating tactics should rely on female availability that males might assess through volatile sex pheromones emitted by virgin females. We predict that in response to those female cues, males of A. bruennichi should mature earlier and at a smaller body size and favor a bigynous mating tactic in comparison with controls. We sampled spiders from two areas close to the Southern and Northern species range to account for differences in mate quality and seasonality. In a fully factorial design, half of the subadult males from both areas obtained silk cues of females, while the other half remained without female exposure. Adult males were subjected to no-choice mating tests and could either monopolize the female or leave her (bigyny). We found that Southern males matured later and at a larger size than Northern males. Regardless of their origin, males also shortened the subadult stage in response to female cues, which, however, had no effects on male body mass. Contrary to our prediction, the frequencies of mating tactics were unaffected by the treatment. We conclude that while social cues during late development elicit adaptive life history adjustments, they are less important for the adjustment of mating decisions. We suggest that male tactics mostly rely on local information at the time of mate search.}, } @article {pmid29321875, year = {2018}, author = {Lintunen, A and Mayr, S and Salmon, Y and Cochard, H and Hölttä, T}, title = {Drivers of apoplastic freezing in gymnosperm and angiosperm branches.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {333-343}, pmid = {29321875}, issn = {2045-7758}, abstract = {It is not well understood what determines the degree of supercooling of apoplastic sap in trees, although it determines the number and duration of annual freeze-thaw cycles in a given environment. We studied the linkage between apoplastic ice nucleation temperature, tree water status, and conduit size. We used branches of 10 gymnosperms and 16 angiosperms collected from an arboretum in Helsinki (Finland) in winter and spring. Branches with lower relative water content froze at lower temperatures, and branch water content was lower in winter than in spring. A bench drying experiment with Picea abies confirmed that decreasing branch water potential decreases apoplastic ice nucleation temperature. The studied angiosperms froze on average 2.0 and 1.8°C closer to zero Celsius than the studied gymnosperms during winter and spring, respectively. This was caused by higher relative water content in angiosperms; when branches were saturated with water, apoplastic ice nucleation temperature of gymnosperms increased to slightly higher temperature than that of angiosperms. Apoplastic ice nucleation temperature in sampled branches was positively correlated with xylem conduit diameter as shown before, but saturating the branches removed the correlation. Decrease in ice nucleation temperature decreased the duration of freezing, which could have an effect on winter embolism formation via the time available for gas escape during ice propagation. The apoplastic ice nucleation temperature varied not only between branches but also within a branch between consecutive freeze-thaw cycles demonstrating the stochastic nature of ice nucleation.}, } @article {pmid29321874, year = {2018}, author = {Gosselin, JL and Zabel, RW and Anderson, JJ and Faulkner, JR and Baptista, AM and Sandford, BP}, title = {Conservation planning for freshwater-marine carryover effects on Chinook salmon survival.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {319-332}, pmid = {29321874}, issn = {2045-7758}, abstract = {Experiences of migratory species in one habitat may affect their survival in the next habitat, in what is known as carryover effects. These effects are especially relevant for understanding how freshwater experience affects survival in anadromous fishes. Here, we study the carryover effects of juvenile salmon passage through a hydropower system (Snake and Columbia rivers, northwestern United States). To reduce the direct effect of hydrosystem passage on juveniles, some fishes are transported through the hydrosystem in barges, while the others are allowed to migrate in-river. Although hydrosystem survival of transported fishes is greater than that of their run-of-river counterparts, their relative juvenile-to-adult survival (hereafter survival) can be less. We tested for carryover effects using generalized linear mixed effects models of survival with over 1 million tagged Chinook salmon, Oncorhynchus tshawytscha (Walbaum) (Salmonidae), migrating in 1999-2013. Carryover effects were identified with rear-type (wild vs. hatchery), passage-type (run-of-river vs. transported), and freshwater and marine covariates. Importantly, the Pacific Decadal Oscillation (PDO) index characterizing cool/warm (i.e., productive/nonproductive) ocean phases had a strong influence on the relative survival of rear- and passage-types. Specifically, transportation benefited wild Chinook salmon more in cool PDO years, while hatchery counterparts benefited more in warm PDO years. Transportation was detrimental for wild Chinook salmon migrating early in the season, but beneficial for later season migrants. Hatchery counterparts benefited from transportation throughout the season. Altogether, wild fish could benefit from transportation approximately 2 weeks earlier during cool PDO years, with still a benefit to hatchery counterparts. Furthermore, we found some support for hypotheses related to higher survival with increased river flow, high predation in the estuary and plume areas, and faster migration and development-related increased survival with temperature. Thus, pre- and within-season information on local- and broad-scale conditions across habitats can be useful for planning and implementing real-time conservation programs.}, } @article {pmid29321873, year = {2018}, author = {Zhao, L and Zhang, H and Tian, W and Xu, X}, title = {Identifying compartments in ecological networks based on energy channels.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {309-318}, pmid = {29321873}, issn = {2045-7758}, abstract = {It has been confirmed in many food webs that the interactions between species are divided into "compartments," that is, subgroups of highly interacting taxa with few weak interactions between the subgroups. Many of the current methods for detecting compartments in food webs are borrowed from network theory, which do little to improve our understanding of the mechanisms underpinning them. Therefore, a method based on ecological context is needed. Here, we develop a new method for detecting compartments in food webs based on the reliance of each node on energy derived from basal resources (i.e., producers or decomposers). Additional Monte Carlo simulations were conducted to test the significance of the compartmentalization. Further, we applied a food web dynamics model to test whether the effects of permutation would be retained within a single compartment. The proposed method identified significant compartments in 23 of the 28 empirical food webs that were investigated. We further demonstrated that the effects of node removal were significantly higher within compartments than between compartments. Our methods and results emphasize the importance of energy channels in forming food web structures, which sheds light on the mechanisms of self-organization within food webs.}, } @article {pmid29321872, year = {2018}, author = {Aduse-Poku, K and Molleman, F and Oduro, W and Oppong, SK and Lohman, DJ and Etienne, RS}, title = {Relative contribution of neutral and deterministic processes in shaping fruit-feeding butterfly assemblages in Afrotropical forests.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {296-308}, pmid = {29321872}, issn = {2045-7758}, abstract = {The unified neutral theory of biodiversity and biogeography has gained the status of a quantitative null model for explaining patterns in ecological (meta)communities. The theory assumes that individuals of trophically similar species are functionally equivalent. We empirically evaluate the relative contribution of neutral and deterministic processes in shaping fruit-feeding butterfly assemblages in three tropical forests in Africa, using both direct (confronting the neutral model with species abundance data) and indirect approaches (testing the predictions of neutral theory using data other than species abundance distributions). Abundance data were obtained by sampling butterflies using banana baited traps set at the forest canopy and understorey strata. Our results indicate a clear consistency in the kind of species or species groups observed at either the canopy or understorey in the three studied communities. Furthermore, we found significant correlation between some flight-related morphological traits and species abundance at the forest canopy, but not at the understorey. Neutral theory's contribution to explaining our data lies largely in identifying dispersal limitation as a key process regulating fruit-feeding butterfly community structure. Our study illustrates that using species abundance data alone in evaluating neutral theory can be informative, but is insufficient. Species-level information such as habitat preference, host plants, geographical distribution, and phylogeny is essential in elucidating the processes that regulate biodiversity community structures and patterns.}, } @article {pmid29321871, year = {2018}, author = {Geekiyanage, N and Goodale, UM and Cao, K and Kitajima, K}, title = {Leaf trait variations associated with habitat affinity of tropical karst tree species.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {286-295}, pmid = {29321871}, issn = {2045-7758}, abstract = {Karst hills, that is, jagged topography created by dissolution of limestone and other soluble rocks, are distributed extensively in tropical forest regions, including southern parts of China. They are characterized by a sharp mosaic of water and nutrient availability, from exposed hilltops with poor soil development to valleys with occasional flooding, to which trees show species-specific distributions. Here we report the relationship of leaf functional traits to habitat preference of tropical karst trees. We described leaf traits of 19 tropical tree species in a seasonal karst rainforest in Guangxi Province, China, 12 species in situ and 13 ex situ in a non-karst arboretum, which served as a common garden, with six species sampled in both. We examined how the measured leaf traits differed in relation to species' habitat affinity and evaluated trait consistency between natural habitats vs. the arboretum. Leaf mass per area (LMA) and optical traits (light absorption and reflectance characteristics between 400 and 1,050 nm) showed significant associations with each other and habitats, with hilltop species showing high values of LMA and low values of photochemical reflectance index (PRI). For the six species sampled in both the karst forest and the arboretum, LMA, leaf dry matter content, stomatal density, and vein length per area showed inconsistent within-species variations, whereas some traits (stomatal pore index and lamina thickness) were similar between the two sites. In conclusion, trees specialized in exposed karst hilltops with little soils are characterized by thick leaves with high tissue density indicative of conservative resources use, and this trait syndrome could potentially be sensed remotely with PRI.}, } @article {pmid29321870, year = {2018}, author = {Canales-Aguirre, CB and Seeb, LW and Seeb, JE and Cádiz, MI and Musleh, SS and Arismendi, I and Gajardo, G and Galleguillos, R and Gomez-Uchida, D}, title = {Contrasting genetic metrics and patterns among naturalized rainbow trout (Oncorhynchus mykiss) in two Patagonian lakes differentially impacted by trout aquaculture.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {273-285}, pmid = {29321870}, issn = {2045-7758}, abstract = {Different pathways of propagation and dispersal of non-native species into new environments may have contrasting demographic and genetic impacts on established populations. Repeated introductions of rainbow trout (Oncorhynchus mykiss) to Chile in South America, initially through stocking and later through aquaculture escapes, provide a unique setting to contrast these two pathways. Using a panel of single nucleotide polymorphisms, we found contrasting genetic metrics and patterns among naturalized trout in Lake Llanquihue, Chile's largest producer of salmonid smolts for nearly 50 years, and Lake Todos Los Santos (TLS), a reference lake where aquaculture has been prohibited by law. Trout from Lake Llanquihue showed higher genetic diversity, weaker genetic structure, and larger estimates for the effective number of breeders (Nb) than trout from Lake TLS. Trout from Lake TLS were divergent from Lake Llanquihue and showed marked genetic structure and a significant isolation-by-distance pattern consistent with secondary contact between documented and undocumented stocking events in opposite shores of the lake. Multiple factors, including differences in propagule pressure, origin of donor populations, lake geomorphology, habitat quality or quantity, and life history, may help explain contrasting genetic metrics and patterns for trout between lakes. We contend that high propagule pressure from aquaculture may not only increase genetic diversity and Nb via demographic effects and admixture, but also may impact the evolution of genetic structure and increase gene flow, consistent with findings from artificially propagated salmonid populations in their native and naturalized ranges.}, } @article {pmid29321869, year = {2018}, author = {Leung, C and Angers, B}, title = {Imitating the cost of males: A hypothesis for coexistence of all-female sperm-dependent species and their sexual host.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {266-272}, pmid = {29321869}, issn = {2045-7758}, abstract = {All-female sperm-dependent species are particular asexual organisms that must coexist with a closely related sexual host for reproduction. However, demographic advantages of asexual over sexual species that have to produce male individuals could lead both to extinction. The unresolved question of their coexistence still challenges and fascinates evolutionary biologists. As an alternative hypothesis, we propose those asexual organisms are afflicted by a demographic cost analogous to the production of males to prevent exclusion of the host. Previously proposed hypotheses stated that asexual individuals relied on a lower fecundity than sexual females to cope with demographic advantage. In contrast, we propose that both sexual and asexual species display the same number of offspring, but half of asexual individuals imitate the cost of sex by occupying ecological niches but producing no offspring. Simulations of population growth in closed systems under different demographic scenarios revealed that only the presence of nonreproductive individuals in asexual females can result in long-term coexistence. This hypothesis is supported by the fact that half of the females in some sperm-dependent organisms did not reproduce clonally.}, } @article {pmid29321868, year = {2018}, author = {Luo, Y and Agnarsson, I}, title = {Global mtDNA genetic structure and hypothesized invasion history of a major pest of citrus, Diaphorina citri (Hemiptera: Liviidae).}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {257-265}, pmid = {29321868}, issn = {2045-7758}, abstract = {The Asian citrus psyllid Diaphorina citri Kuwayama is a key pest of citrus as the vector of the bacterium causing the "huanglongbing" disease (HLB). To assess the global mtDNA population genetic structure, and possible dispersal history of the pest, we investigated genetic variation at the COI gene collating newly collected samples with all previously published data. Our dataset consists of 356 colonies from 106 geographic sites worldwide. High haplotype diversity (H-mean = 0.702 ± 0.017), low nucleotide diversity (π-mean = 0.003), and significant positive selection (Ka/Ks = 32.92) were observed. Forty-four haplotypes (Hap) were identified, clustered into two matrilines: Both occur in southeastern and southern Asia, North and South America, and Africa; lineages A and B also occur in eastern and western Asia, respectively. The most abundant haplotypes were Hap4 in lineage A (35.67%), and Hap9 in lineage B (41.29%). The haplotype network identified them as the ancestral haplotypes within their respective lineages. Analysis of molecular variance showed significant genetic structure (FST = 0.62, p < .0001) between the lineages, and population genetic analysis suggests geographic structuring. We hypothesize a southern and/or southeastern Asia origin, three dispersal routes, and parallel expansions of two lineages. The hypothesized first route involved the expansion of lineage B from southern Asia into North America via West Asia. The second, the expansion of some lineage A individuals from Southeast Asia into East Asia, and the third involved both lineages from Southeast Asia spreading westward into Africa and subsequently into South America. To test these hypotheses and gain a deeper understanding of the global history of D. citri, more data-rich approaches will be necessary from the ample toolkit of next-generation sequencing (NGS). However, this study may serve to guide such sampling and in the development of biological control programs against the global pest D. citri.}, } @article {pmid29321867, year = {2018}, author = {Passadore, C and Möller, L and Diaz-Aguirre, F and Parra, GJ}, title = {High site fidelity and restricted ranging patterns in southern Australian bottlenose dolphins.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {242-256}, pmid = {29321867}, issn = {2045-7758}, abstract = {Information on site fidelity and ranging patterns of wild animals is critical to understand how they use their environment and guide conservation and management strategies. Delphinids show a wide variety of site fidelity and ranging patterns. Between September 2013 and October 2015, we used boat-based surveys, photographic identification, biopsy sampling, clustering analysis, and geographic information systems to determine the site-fidelity patterns and representative ranges of southern Australian bottlenose dolphins (Tursiops cf. australis) inhabiting the inner area of Coffin Bay, a highly productive inverse estuary located within Thorny Passage Marine Park, South Australia. Agglomerative hierarchical clustering (AHC) of individuals' site-fidelity index and sighting rates indicated that the majority of dolphins within the inner area of Coffin Bay are "regular residents" (n = 125), followed by "occasional residents" (n = 28), and "occasional visitors" (n = 26). The low standard distance deviation indicated that resident dolphins remained close to their main center of use (range = 0.7-4.7 km, X ± SD = 2.3 ± 0.9 km). Representative ranges of resident dolphins were small (range = 3.9-33.5 km2, X ± SD = 15.2 ± 6.8 km2), with no significant differences between males and females (Kruskal-Wallis, χ2 = 0.426, p = .808). The representative range of 56% of the resident dolphins was restricted to a particular bay within the study area. The strong site fidelity and restricted ranging patterns among individuals could be linked to the high population density of this species in the inner area of Coffin Bay, coupled with differences in social structure and feeding habits. Our results emphasize the importance of productive habitats as a major factor driving site fidelity and restricted movement patterns in highly mobile marine mammals and the high conservation value of the inner area of Coffin Bay for southern Australian bottlenose dolphins.}, } @article {pmid29321866, year = {2018}, author = {Ren, H and Taube, F and Stein, C and Zhang, Y and Bai, Y and Hu, S}, title = {Grazing weakens temporal stabilizing effects of diversity in the Eurasian steppe.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {231-241}, pmid = {29321866}, issn = {2045-7758}, abstract = {Many biodiversity experiments have demonstrated that plant diversity can stabilize productivity in experimental grasslands. However, less is known about how diversity-stability relationships are mediated by grazing. Grazing is known for causing species losses, but its effects on plant functional groups (PFGs) composition and species asynchrony, which are closely correlated with ecosystem stability, remain unclear. We conducted a six-year grazing experiment in a semi-arid steppe, using seven levels of grazing intensity (0, 1.5, 3.0, 4.5, 6.0, 7.5, and 9.0 sheep per hectare) and two grazing systems (i.e., a traditional, continuous grazing system during the growing period (TGS), and a mixed one rotating grazing and mowing annually (MGS)), to examine the effects of grazing system and grazing intensity on the abundance and composition of PFGs and diversity-stability relationships. Ecosystem stability was similar between mixed and continuous grazing treatments. However, within the two grazing systems, stability was maintained through different pathways, that is, along with grazing intensity, persistence biomass variations in MGS, and compensatory interactions of PFGs in their biomass variations in TGS. Ecosystem temporal stability was not decreased by species loss but rather remain unchanged by the strong compensatory effects between PFGs, or a higher grazing-induced decrease in species asynchrony at higher diversity, and a higher grazing-induced increase in the temporal variation of productivity in diverse communities. Ecosystem stability of aboveground net primary production was not related to species richness in both grazing systems. High grazing intensity weakened the temporal stabilizing effects of diversity in this semi-arid grassland. Our results demonstrate that the productivity of dominant PFGs is more important than species richness for maximizing stability in this system. This study distinguishes grazing intensity and grazing system from diversity effects on the temporal stability, highlighting the need to better understand how grazing regulates ecosystem stability, plant diversity, and their synergic relationships.}, } @article {pmid29321865, year = {2018}, author = {Xue, H and Tang, H}, title = {Responses of soil respiration to soil management changes in an agropastoral ecotone in Inner Mongolia, China.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {220-230}, pmid = {29321865}, issn = {2045-7758}, abstract = {Studying the responses of soil respiration (Rs) to soil management changes is critical for enhancing our understanding of the global carbon cycle and has practical implications for grassland management. Therefore, the objectives of this study were (1) quantify daily and seasonal patterns of Rs, (2) evaluate the influence of abiotic factors on Rs, and (3) detect the effects of soil management changes on Rs. We hypothesized that (1) most of daily and seasonal variation in Rs could be explained by soil temperature (Ts) and soil water content (Sw), (2) soil management changes could significantly affect Rs, and (3) soil management changes affected Rs via the significant change in abiotic and biotic factors. In situ Rs values were monitored in an agropastoral ecotone in Inner Mongolia, China, during the growing seasons in 2009 (August to October) and 2010 (May to October). The soil management changes sequences included free grazing grassland (FG), cropland (CL), grazing enclosure grassland (GE), and abandoned cultivated grassland (AC). During the growing season in 2010, cumulative Rs for FG, CL, GE, and AC averaged 265.97, 344.74, 236.70, and 226.42 gC m-2 year-1, respectively. The Ts and Sw significantly influenced Rs and explained 66%-86% of the variability in daily Rs. Monthly mean temperature and precipitation explained 78%-96% of the variability in monthly Rs. The results clearly showed that Rs was increased by 29% with the conversion of FG to CL and decreased by 35% and 11% with the conversion of CL to AC and FG to GE. The factors impacting the change in Rs under different soil management changes sequences varied. Our results confirm the tested hypotheses. The increase in Q10 and litter biomass induced by conversion of FG to GE could lead to increased Rs if the climate warming. We suggest that after proper natural restoration period, grasslands should be utilized properly to decrease Rs.}, } @article {pmid29321864, year = {2018}, author = {da Silva, J}, title = {The evolution of sexes: A specific test of the disruptive selection theory.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {207-219}, pmid = {29321864}, issn = {2045-7758}, abstract = {The disruptive selection theory of the evolution of anisogamy posits that the evolution of a larger body or greater organismal complexity selects for a larger zygote, which in turn selects for larger gametes. This may provide the opportunity for one mating type to produce more numerous, small gametes, forcing the other mating type to produce fewer, large gametes. Predictions common to this and related theories have been partially upheld. Here, a prediction specific to the disruptive selection theory is derived from a previously published game-theoretic model that represents the most complete description of the theory. The prediction, that the ratio of macrogamete to microgamete size should be above three for anisogamous species, is supported for the volvocine algae. A fully population genetic implementation of the model, involving mutation, genetic drift, and selection, is used to verify the game-theoretic approach and accurately simulates the evolution of gamete sizes in anisogamous species. This model was extended to include a locus for gamete motility and shows that oogamy should evolve whenever there is costly motility. The classic twofold cost of sex may be derived from the fitness functions of these models, showing that this cost is ultimately due to genetic conflict.}, } @article {pmid29321863, year = {2018}, author = {Lee, SG and Kim, SK and Lee, HJ and Lee, HS and Lee, JH}, title = {Impact of moderate and extreme climate change scenarios on growth, morphological features, photosynthesis, and fruit production of hot pepper.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {197-206}, pmid = {29321863}, issn = {2045-7758}, abstract = {Horticultural crop production and changes in physiological aspects during the growing season may be affected by climate change factors (CC), which include increased temperature and the associated doubling or tripling of atmospheric CO2 concentrations. However, the potential effects are complex and many parameters might impact on the observed effects. To evaluate the effects of CC, the growth, yield, fruit characteristics, photosynthetic traits, and morphological characteristics of hot peppers were investigated. The hot peppers were grown under two CC scenarios, with the Representative Concentration Pathway (RCP) of 4.5 (Temp.; +3.4°C, CO2 conc.; 540 μmol/mol, Precipitation +17.3%) and RCP 8.5 (Temp.; +6.0°C and CO2 conc.; 940 μmol/mol, Precipitation +20.3%), respectively, using extreme weather simulators. This was compared with existing weather conditions occurring in Jeonju, South Korea in terms of air temperature, relative humidity, radiation, and precipitation. Overall, the plant height showed the highest under moderate CC conditions (RCP 4.5) among all the treatments tested. The number of leaves in the RCP 8.5 condition showed 7,739/plants, which was 2.2 times higher than that of the control. In addition, fruit shape was shortened and percentage dry matter was also the highest. The yield of hot pepper in the CC RCP 4.5 and 8.5 conditions were decreased by 21.5% and 89.2% when compared with that of the control, respectively. The days to harvest in the condition of CC scenarios were shortened from 5 to 13 compared with that of control, predominantly due to the increased air temperature. The results indicated that the severe RCP CC scenarios made reduction in the yields and negative affection on the fruit qualities. Overall, hot pepper was tolerant of mild CC scenarios of temperature × CO2 but was significantly affected by more extreme CC interacting parameter concentrations (or similar).}, } @article {pmid29321862, year = {2018}, author = {Robeson, MS and Khanipov, K and Golovko, G and Wisely, SM and White, MD and Bodenchuck, M and Smyser, TJ and Fofanov, Y and Fierer, N and Piaggio, AJ}, title = {Assessing the utility of metabarcoding for diet analyses of the omnivorous wild pig (Sus scrofa).}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {185-196}, pmid = {29321862}, issn = {2045-7758}, abstract = {Wild pigs (Sus scrofa) are an invasive species descended from both domestic swine and Eurasian wild boar that was introduced to North America during the early 1500s. Wild pigs have since become the most abundant free-ranging exotic ungulate in the United States. Large and ever-increasing populations of wild pigs negatively impact agriculture, sport hunting, and native ecosystems with costs estimated to exceed $1.5 billion/year within the United States. Wild pigs are recognized as generalist feeders, able to exploit a broad array of locally available food resources, yet their feeding behaviors remain poorly understood as partially digested material is often unidentifiable through traditional stomach content analyses. To overcome the limitation of stomach content analyses, we developed a DNA sequencing-based protocol to describe the plant and animal diet composition of wild pigs. Additionally, we developed and evaluated blocking primers to reduce the amplification and sequencing of host DNA, thus providing greater returns of sequences from diet items. We demonstrate that the use of blocking primers produces significantly more sequencing reads per sample from diet items, which increases the robustness of ascertaining animal diet composition with molecular tools. Further, we show that the overall plant and animal diet composition is significantly different between the three areas sampled, demonstrating this approach is suitable for describing differences in diet composition among the locations.}, } @article {pmid29321861, year = {2018}, author = {Bialic-Murphy, L and Gaoue, OG}, title = {Low interannual precipitation has a greater negative effect than seedling herbivory on the population dynamics of a short-lived shrub, Schiedea obovata.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {176-184}, pmid = {29321861}, issn = {2045-7758}, abstract = {Climate projections forecast more extreme interannual climate variability over time, with an increase in the severity and duration of extreme drought and rainfall events. Based on bioclimatic envelope models, it is projected that changing precipitation patterns will drastically alter the spatial distributions and density of plants and be a primary driver of biodiversity loss. However, many other underlying mechanisms can impact plant vital rates (i.e., survival, growth, and reproduction) and population dynamics. In this study, we developed a size-dependent integral projection model (IPM) to evaluate how interannual precipitation and mollusk herbivory influence the dynamics of a Hawaii endemic short-lived shrub, Schiedea obovata (Caryophyllaceae). Assessing how wet season precipitation effects population dynamics it critical, as it is the timeframe when most of the foliar growth occurs, plants flower and fruit, and seedlings establish. Temporal variation in wet season precipitation had a greater effect than mollusk herbivory on S. obovata population growth rate λ, and the impact of interannual precipitation on vital rates shifted across plant ontogeny. Furthermore, wet season precipitation influenced multiple vital rates in contrasting ways and the effect of precipitation on the survival of larger vegetative and reproductively mature individuals contributed the most to variation in the population growth rate. Among all combination of wet season precipitation and herbivory intensities, the only scenario that led to a growing population was when high wet precipitation was associated with low herbivory. Our study highlights the importance of evaluating how abiotic factors and plant-consumer interactions influence an organism across its life cycle to fully understand the underpinning mechanisms that structure its spatial and temporal distribution and abundance. Our results also illustrate that for short-lived species, like S. obovata, seedling herbivory can have less of an effect on the dynamics of plant populations than decreased interannual precipitation.}, } @article {pmid29321860, year = {2018}, author = {Goodsman, DW and Aukema, BH and McDowell, NG and Middleton, RS and Xu, C}, title = {Incorporating variability in simulations of seasonally forced phenology using integral projection models.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {162-175}, pmid = {29321860}, issn = {2045-7758}, abstract = {Phenology models are becoming increasingly important tools to accurately predict how climate change will impact the life histories of organisms. We propose a class of integral projection phenology models derived from stochastic individual-based models of insect development and demography. Our derivation, which is based on the rate summation concept, produces integral projection models that capture the effect of phenotypic rate variability on insect phenology, but which are typically more computationally frugal than equivalent individual-based phenology models. We demonstrate our approach using a temperature-dependent model of the demography of the mountain pine beetle (Dendroctonus ponderosae Hopkins), an insect that kills mature pine trees. This work illustrates how a wide range of stochastic phenology models can be reformulated as integral projection models. Due to their computational efficiency, these integral projection models are suitable for deployment in large-scale simulations, such as studies of altered pest distributions under climate change.}, } @article {pmid29321859, year = {2018}, author = {Tudela-Isanta, M and Fernández-Pascual, E and Wijayasinghe, M and Orsenigo, S and Rossi, G and Pritchard, HW and Mondoni, A}, title = {Habitat-related seed germination traits in alpine habitats.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {150-161}, pmid = {29321859}, issn = {2045-7758}, abstract = {Understanding the key aspects of plant regeneration from seeds is crucial in assessing species assembly to their habitats. However, the regenerative traits of seed dormancy and germination are underrepresented in this context. In the alpine zone, the large species and microhabitat diversity provide an ideal context to assess habitat-related regenerative strategies. To this end, seeds of 53 species growing in alpine siliceous and calcareous habitats (6230 and 6170 of EU Directive 92/43, respectively) were exposed to different temperature treatments under controlled laboratory conditions. Germination strategies in each habitat were identified by clustering with k-means. Then, phylogenetic least squares correlations (PGLS) were fitted to assess germination and dormancy differences between species' main habitat (calcareous and siliceous), microhabitat (grasslands, heaths, rocky, and species with no specific microhabitats), and chorology (arctic-alpine and continental). Calcareous and siliceous grasslands significantly differ in their germination behaviour with a slow, mostly overwinter germination and high germination under all conditions, respectively. Species with high overwinter germination occurs mostly in heaths and have an arctic-alpine distribution. Meanwhile, species with low or high germinability in general inhabit in grasslands or have no specific microhabitat (they belong to generalist), respectively. Alpine species use different germination strategies depending on habitat provenance, species' main microhabitat, and chorotype. Such differences may reflect adaptations to local environmental conditions and highlight the functional role of germination and dormancy in community ecology.}, } @article {pmid29321858, year = {2018}, author = {Ait Mouheb, H and Kadik, L and Albert, CH and Berrached, R and Prinzing, A}, title = {How do steppe plants follow their optimal environmental conditions or persist under suboptimal conditions? The differing strategies of annuals and perennials.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {135-149}, pmid = {29321858}, issn = {2045-7758}, abstract = {For a species to be able to respond to environmental change, it must either succeed in following its optimal environmental conditions or in persisting under suboptimal conditions, but we know very little about what controls these capacities. We parameterized species distribution models (SDMs) for 135 plant species from the Algerian steppes. We interpreted low false-positive rates as reflecting a high capacity to follow optimal environmental conditions and high false-negative rates as a high capacity to persist under suboptimal environmental conditions. We also measured functional traits in the field and built a unique plant trait database for the North-African steppe. For both perennial and annual species, we explored how these two capacities can be explained by species traits and whether relevant trait values reflect species strategies or biases in SDMs. We found low false-positive rates in species with small seeds, flowers attracting specialist pollinators, and specialized distributions (among annuals and perennials), low root:shoot ratios, wide root-systems, and large leaves (perennials only) (R2 = .52-58). We found high false-negative rates in species with marginal environmental distribution (among annuals and perennials), small seeds, relatively deep roots, and specialized distributions (annuals) or large leaves, wide root-systems, and monocarpic life cycle (perennials) (R2 = .38 for annuals and 0.65 for perennials). Overall, relevant traits are rarely indicative of the possible biases of SDMs, but rather reflect the species' reproductive strategy, dispersal ability, stress tolerance, and pollination strategies. Our results suggest that wide undirected dispersal in annual species and efficient resource acquisition in perennial species favor both capacities, whereas short life spans in perennial species favor persistence in suboptimal environmental conditions and flowers attracting specialist pollinators in perennial and annual species favor following optimal environmental conditions. Species that neither follow nor persist will be at risk under future environmental change.}, } @article {pmid29321857, year = {2018}, author = {Seidel, D}, title = {A holistic approach to determine tree structural complexity based on laser scanning data and fractal analysis.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {128-134}, pmid = {29321857}, issn = {2045-7758}, abstract = {The three-dimensional forest structure affects many ecosystem functions and services provided by forests. As forests are made of trees it seems reasonable to approach their structure by investigating individual tree structure. Based on three-dimensional point clouds from laser scanning, a newly developed holistic approach is presented that enables to calculate the box dimension as a measure of structural complexity of individual trees using fractal analysis. It was found that the box dimension of trees was significantly different among the tested species, among trees belonging to the same species but exposed to different growing conditions (at gap vs. forest interior) or to different kinds of competition (intraspecific vs. interspecific). Furthermore, it was shown that the box dimension is positively related to the trees' growth rate. The box dimension was identified as an easy to calculate measure that integrates the effect of several external drivers of tree structure, such as competition strength and type, while simultaneously providing information on structure-related properties, like tree growth.}, } @article {pmid29321856, year = {2018}, author = {Wang, Y and Wen, S and Farnon Ellwood, MD and Miller, AD and Chu, C}, title = {Temporal effects of disturbance on community composition in simulated stage-structured plant communities.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {120-127}, pmid = {29321856}, issn = {2045-7758}, abstract = {In an era of global environmental change, understanding how disturbance affects the dynamics of ecological communities is crucial. However, few studies have theoretically explored the potential influence of disturbance including both intensity and frequency on compositional change over time in communities with stage structure. A spatially explicit, individual-based model was constructed incorporating the various demographic responses to disturbance of plants at two different growth stages: seedlings and adults. In the model, we assumed that individuals within each stage were demographically equivalent (neutral) but differed between stages. We simulated a common phenomenon that seedlings suffered more from disturbance such as grazing and fire than adults. We showed how stage-structured communities of seedlings and adults responded to disturbance with various levels of disturbance frequency and intensity. In "undisturbed" simulations, the relationship between average species abundance (defined here as the total number of individuals divided by species richness) and community composition turnover (measured by the Bray-Curtis similarity index) was asymptotic. However, in strongly "disturbed" simulations with the between-disturbance intervals greater than one, this relationship became unimodal. Stage-dependent response to disturbance underlay the above discrepancy between undisturbed and disturbed communities.}, } @article {pmid29321855, year = {2018}, author = {Gehr, B and Hofer, EJ and Pewsner, M and Ryser, A and Vimercati, E and Vogt, K and Keller, LF}, title = {Hunting-mediated predator facilitation and superadditive mortality in a European ungulate.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {109-119}, pmid = {29321855}, issn = {2045-7758}, abstract = {Predator-prey theory predicts that in the presence of multiple types of predators using a common prey, predator facilitation may result as a consequence of contrasting prey defense mechanisms, where reducing the risk from one predator increases the risk from the other. While predator facilitation is well established in natural predator-prey systems, little attention has been paid to situations where human hunters compete with natural predators for the same prey. Here, we investigate hunting-mediated predator facilitation in a hunter-predator-prey system. We found that hunter avoidance by roe deer (Capreolus capreolus) exposed them to increase predation risk by Eurasian lynx (Lynx lynx). Lynx responded by increasing their activity and predation on deer, providing evidence that superadditive hunting mortality may be occurring through predator facilitation. Our results reveal a new pathway through which human hunters, in their role as top predators, may affect species interactions at lower trophic levels and thus drive ecosystem processes.}, } @article {pmid29321854, year = {2018}, author = {Menezes, T and Romeiras, MM and de Sequeira, MM and Moura, M}, title = {Phylogenetic relationships and phylogeography of relevant lineages within the complex Campanulaceae family in Macaronesia.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {88-108}, pmid = {29321854}, issn = {2045-7758}, abstract = {Macaronesia has long been recognized as a natural model for studying evolutionary processes in plant diversification. Several studies have attempted to focus on single lineages, and few have covered the diversification of a family across all the archipelagos. We used a comprehensive sample to clarify the phylogenetic relationships and the biogeographic history of the Macaronesian Campanulaceae. Hypotheses related to the colonization of these archipelagos will be used to examine the diversification patterns of different lineages. We sequenced the ITS region and six cpDNA markers (atpB, matK, petD, rbcL, trnL-F, and psbA-trnH) from 10 Campanulaceae species, including seven endemic species in Macaronesia. The phylogeny of these taxa was reconstructed using maximum parsimony, maximum likelihood, and Bayesian inference. To study the relationships within each lineage, haplotype networks were calculated using NeighborNet and TCS algorithms. Moreover, data were combined with fossil information to construct time-calibrated trees for the Macaronesian Campanulaceae species. The phylogenetic analyses are largely congruent with current taxon circumscriptions, and all the endemic genera formed monophyletic clades, namely Azorina in Azores; Musschia in Madeira; and Campanula in Cape Verde. The Azorina clade and the Cape Verde endemic Campanula may share a common ancestor in North Africa, and the divergence was dated ca. 12.3 million years ago (Mya). The divergence of the Musschia clade began in the Pliocene ca. 3.4 Mya. Moreover, several examples of intraspecific variation were revealed among the native species with a clear geographic structured patterns, suggesting that cryptic diversity might exist within the native Macaronesian Campanulaceae when compared to the close mainland taxa (e.g., Campanula erinus, Trachelium caeruleum), but additional studies are needed to support the molecular data. This study highlights the power of combining data (e.g., phylogeny and divergence times, with species distribution data) for testing diversification hypotheses within the unique Macaronesian flora, providing useful information for future conservation efforts.}, } @article {pmid29321853, year = {2018}, author = {Werner, GDA and Zhou, Y and Pieterse, CMJ and Kiers, ET}, title = {Tracking plant preference for higher-quality mycorrhizal symbionts under varying CO2 conditions over multiple generations.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {78-87}, pmid = {29321853}, issn = {2045-7758}, abstract = {The symbiosis between plants and root-colonizing arbuscular mycorrhizal (AM) fungi is one of the most ecologically important examples of interspecific cooperation in the world. AM fungi provide benefits to plants; in return plants allocate carbon resources to fungi, preferentially allocating more resources to higher-quality fungi. However, preferential allocations from plants to symbionts may vary with environmental context, particularly when resource availability affects the relative value of symbiotic services. We ask how differences in atmospheric CO 2-levels influence root colonization dynamics between AMF species that differ in their quality as symbiotic partners. We find that with increasing CO 2-conditions and over multiple plant generations, the more beneficial fungal species is able to achieve a relatively higher abundance. This suggests that increasing atmospheric carbon supply enables plants to more effectively allocate carbon to higher-quality mutualists, and over time helps reduce lower-quality AM abundance. Our results illustrate how environmental context may affect the extent to which organisms structure interactions with their mutualistic partners and have potential implications for mutualism stability and persistence under global change.}, } @article {pmid29321852, year = {2018}, author = {Field, JM and Bonsall, MB}, title = {Ignorance can be evolutionarily beneficial.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {71-77}, pmid = {29321852}, issn = {2045-7758}, abstract = {Information is increasingly being viewed as a resource used by organisms to increase their fitness. Indeed, it has been formally shown that there is a sensible way to assign a reproductive value to information and it is non-negative. However, all of this work assumed that information collection is cost-free. Here, we account for such a cost and provide conditions for when the reproductive value of information will be negative. In these instances, counterintuitively, it is in the interest of the organism to remain ignorant. We link our results to empirical studies where Bayesian behavior appears to break down in complex environments and provide an alternative explanation of lowered arousal thresholds in the evolution of sleep.}, } @article {pmid29321851, year = {2018}, author = {Liu, M and Zhou, F and Pan, X and Zhang, Z and Traw, MB and Li, B}, title = {Specificity of herbivore-induced responses in an invasive species, Alternanthera philoxeroides (alligator weed).}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {59-70}, pmid = {29321851}, issn = {2045-7758}, abstract = {Herbivory-induced responses in plants can both negatively affect subsequently colonizing herbivores and mitigate the effect of herbivory on the host. However, it is still less known whether plants exhibit specific responses to specialist and generalist herbivores in non-secondary metabolite traits and how specificity to specialists and generalists differs between invasive and native plant populations. We exposed an invasive plant, Alternanthera philoxeroides, to Agasicles hygrophila (Coleoptera, Chrysomelidae; specialist), Spodoptera litura (Lepidoptera, Noctuidae; generalist), manual clipping, or application of exogenous jasmonic acid and examined both the specificity of elicitation in traits of fitness (e.g., aboveground biomass), morphology (e.g., root:shoot ratio), and chemistry (e.g., C/N ratio and lignin), and specificity of effect on the subsequent performance of A. hygrophila and S. litura. Then, we assessed variation of the specificity between invasive and native populations (USA and Argentina, respectively). The results showed S. litura induced higher branching intensity and specific leaf area but lower C/N ratio than A. hygrophila, whereas A. hygrophila induced higher trichome density than S. litura. The negative effect of induction on subsequent larval growth was greater for S. litura than for A. hygrophila. Invasive populations had a weaker response to S. litura than to A. hygrophila in triterpenoid saponins and C/N ratio, while native populations responded similarly to these two herbivores. The specific effect on the two herbivores feeding on induced plants did not vary between invasive and native populations. Overall, we demonstrate specificity of elicitation to specialist and generalist herbivores in non-secondary metabolite traits, and that the generalist is more susceptible to induction than the specialist. Furthermore, chemical responses specific to specialist and generalist herbivores only exist in the invasive populations, consistent with an evolutionary change in specificity in the invasive populations.}, } @article {pmid29321850, year = {2018}, author = {Liang, C and Feng, G and Si, X and Mao, L and Yang, G and Svenning, JC and Yang, J}, title = {Bird species richness is associated with phylogenetic relatedness, plant species richness, and altitudinal range in Inner Mongolia.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {53-58}, pmid = {29321850}, issn = {2045-7758}, support = {310886//European Research Council/International ; }, abstract = {Bird species richness is mediated by local, regional, and historical factors, for example, competition, environmental heterogeneity, contemporary, and historical climate. Here, we related bird species richness with phylogenetic relatedness of bird assemblages, plant species richness, topography, contemporary climate, and glacial-interglacial climate change to investigate the relative importance of these factors. This study was conducted in Inner Mongolia, an arid and semiarid region with diverse vegetation types and strong species richness gradients. The following associated variables were included as follows: phylogenetic relatedness of bird assemblages (Net Relatedness Index, NRI), plant species richness, altitudinal range, contemporary climate (mean annual temperature and precipitation, MAT and MAP), and contemporary-Last Glacial Maximum (LGM) change in climate (change in MAT and change in MAP). Ordinary least squares linear, simultaneous autoregressive linear, and Random Forest models were used to assess the associations between these variables and bird species richness across this region. We found that bird species richness was correlated negatively with NRI and positively with plant species richness and altitudinal range, with no significant correlations with contemporary climate and glacial-interglacial climate change. The six best combinations of variables ranked by Random Forest models consistently included NRI, plant species richness, and contemporary-LGM change in MAT. Our results suggest important roles of local ecological factors in shaping the distribution of bird species richness across this semiarid region. Our findings highlight the potential importance of these local ecological factors, for example, environmental heterogeneity, habitat filtering, and biotic interactions, in biodiversity maintenance.}, } @article {pmid29321849, year = {2018}, author = {Burns, M and Hedin, M and Tsurusaki, N}, title = {Population genomics and geographical parthenogenesis in Japanese harvestmen (Opiliones, Sclerosomatidae, Leiobunum).}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {36-52}, pmid = {29321849}, issn = {2045-7758}, abstract = {Naturally occurring population variation in reproductive mode presents an opportunity for researchers to test hypotheses regarding the evolution of sex. Asexual reproduction frequently assumes a geographical pattern, in which parthenogenesis-dominated populations are more broadly dispersed than their sexual conspecifics. We evaluate the geographical distribution of genomic signatures associated with parthenogenesis using nuclear and mitochondrial DNA sequence data from two Japanese harvestman sister taxa, Leiobunum manubriatum and Leiobunum globosum. Asexual reproduction is putatively facultative in these species, and female-biased localities are common in habitat margins. Past karyotypic and current cytometric work indicates L. globosum is entirely tetraploid, while L. manubriatum may be either diploid or tetraploid. We estimated species phylogeny, genetic differentiation, diversity, and mitonuclear discordance in females collected across the species range in order to identify range expansion toward marginal habitat, potential for hybrid origin, and persistence of asexual lineages. Our results point to northward expansion of a tetraploid ancestor of L. manubriatum and L. globosum, coupled with support for greater male gene flow in southern L. manubriatum localities. Specimens from localities in the Tohoku and Hokkaido regions were indistinct, particularly those of L. globosum, potentially due to little mitochondrial differentiation or haplotypic variation. Although L. manubriatum overlaps with L. globosum across its entire range, L. globosum was reconstructed as monophyletic with strong support using mtDNA, and marginal support with nuclear loci. Ultimately, we find evidence for continued sexual reproduction in both species and describe opportunities to clarify the rate and mechanism of parthenogenesis.}, } @article {pmid29321848, year = {2018}, author = {Winchell, KM and Carlen, EJ and Puente-Rolón, AR and Revell, LJ}, title = {Divergent habitat use of two urban lizard species.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {25-35}, pmid = {29321848}, issn = {2045-7758}, abstract = {Faunal responses to anthropogenic habitat modification represent an important aspect of global change. In Puerto Rico, two species of arboreal lizard, Anolis cristatellus and A. stratulus, are commonly encountered in urban areas, yet seem to use the urban habitat in different ways. In this study, we quantified differences in habitat use between these two species in an urban setting. For each species, we measured habitat use and preference, and the niche space of each taxon, with respect to manmade features of the urban environment. To measure niche space of these species in an urban environment, we collected data from a total of six urban sites across four different municipalities on the island of Puerto Rico. We quantified relative abundance of both species, their habitat use, and the available habitat in the environment to measure both microhabitat preference in an urban setting, as well as niche partitioning between the two different lizards. Overall, we found that the two species utilize different portions of the urban habitat. Anolis stratulus tends to use more "natural" portions of the urban environment (i.e., trees and other cultivated vegetation), whereas A. cristatellus more frequently uses anthropogenic structures. We also found that aspects of habitat discrimination in urban areas mirror a pattern measured in prior studies for forested sites in which A. stratulus was found to perch higher than A. cristatellus and preferred lower temperatures and greater canopy cover. In our study, we found that the multivariate niche space occupied by A. stratulus did not differ from the available niche space in natural portions of the urban environment and in turn represented a subset of the niche space occupied by A. cristatellus. The unique niche space occupied by A. cristatellus corresponds to manmade aspects of the urban environment generally not utilized by A. stratulus. Our results demonstrate that some species are merely tolerant of urbanization while others utilize urban habitats in novel ways. This finding has implications for long-term persistence in urban habitats and suggests that loss of natural habitat elements may lead to nonrandom species extirpations as urbanization intensifies.}, } @article {pmid29321847, year = {2018}, author = {Bennison, A and Bearhop, S and Bodey, TW and Votier, SC and Grecian, WJ and Wakefield, ED and Hamer, KC and Jessopp, M}, title = {Search and foraging behaviors from movement data: A comparison of methods.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {13-24}, pmid = {29321847}, issn = {2045-7758}, abstract = {Search behavior is often used as a proxy for foraging effort within studies of animal movement, despite it being only one part of the foraging process, which also includes prey capture. While methods for validating prey capture exist, many studies rely solely on behavioral annotation of animal movement data to identify search and infer prey capture attempts. However, the degree to which search correlates with prey capture is largely untested. This study applied seven behavioral annotation methods to identify search behavior from GPS tracks of northern gannets (Morus bassanus), and compared outputs to the occurrence of dives recorded by simultaneously deployed time-depth recorders. We tested how behavioral annotation methods vary in their ability to identify search behavior leading to dive events. There was considerable variation in the number of dives occurring within search areas across methods. Hidden Markov models proved to be the most successful, with 81% of all dives occurring within areas identified as search. k-Means clustering and first passage time had the highest rates of dives occurring outside identified search behavior. First passage time and hidden Markov models had the lowest rates of false positives, identifying fewer search areas with no dives. All behavioral annotation methods had advantages and drawbacks in terms of the complexity of analysis and ability to reflect prey capture events while minimizing the number of false positives and false negatives. We used these results, with consideration of analytical difficulty, to provide advice on the most appropriate methods for use where prey capture behavior is not available. This study highlights a need to critically assess and carefully choose a behavioral annotation method suitable for the research question being addressed, or resulting species management frameworks established.}, } @article {pmid29321846, year = {2018}, author = {Silva, JLA and Souza, AF and Caliman, A and Voigt, EL and Lichston, JE}, title = {Weak whole-plant trait coordination in a seasonally dry South American stressful environment.}, journal = {Ecology and evolution}, volume = {8}, number = {1}, pages = {4-12}, pmid = {29321846}, issn = {2045-7758}, abstract = {A core question involving both plant physiology and community ecology is whether traits from different organs are coordinated across species, beyond pairwise trait correlations. The strength of within-community trait coordination has been hypothesized to increase along gradients of environmental harshness, due to the cost of adopting ecological strategies out of the viable niche space supported by the abiotic conditions. We evaluated the strength of trait relationship and coordination in a stressful environment using 21 leaf and stem traits of 21 deciduous and evergreen woody species from a heath vegetation growing on coastal sandy plain in northeastern South America. The study region faces marked dry season, high soil salinity and acidity, and poor nutritional conditions. Results from multiple factor analyses supported two weak and independent axes of trait coordination, which accounted for 25%-29% of the trait variance using phylogenetically independent contrasts. Trait correlations on the multiple factor analyses main axis fit well with the global plant economic spectrum, with species investing in small leaves and dense stems as opposed to species with softer stems and large leaves. The species' positions on the main functional axis corresponded to the competitor-stress-tolerant side of Grime's CSR triangle of plant strategies. The weak degree of trait coordination displayed by the heath vegetation species contradicted our expectation of high trait coordination in stressful environmental habitats. The distinct biogeographic origins of the species occurring in the study region and the prevalence of a regional environmental filter coupled with local homogeneous conditions could account for prevalence of trait independence we observed.}, } @article {pmid29321060, year = {2018}, author = {Langille, MGI and Ravel, J and Fricke, WF}, title = {"Available upon request": not good enough for microbiome data!.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {8}, pmid = {29321060}, issn = {2049-2618}, mesh = {Biomedical Research ; Genomics ; Humans ; *Information Dissemination ; *Microbiota ; }, } @article {pmid29321059, year = {2018}, author = {Habets, B and Staal, JB and Tijssen, M and van Cingel, R}, title = {Intrarater reliability of the Humac NORM isokinetic dynamometer for strength measurements of the knee and shoulder muscles.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {15}, pmid = {29321059}, issn = {1756-0500}, mesh = {Adult ; Biomechanical Phenomena/*physiology ; Female ; Humans ; Knee/*physiology ; Male ; Muscle Strength/*physiology ; Muscle Strength Dynamometer/*standards ; Muscle, Skeletal/*physiology ; Reproducibility of Results ; Shoulder/*physiology ; Young Adult ; }, abstract = {OBJECTIVE: To determine the intrarater reliability of the Humac NORM isokinetic dynamometer for concentric and eccentric strength tests of knee and shoulder muscles.

RESULTS: 54 participants (50% female, average age 20.9 ± 3.1 years) performed concentric and eccentric strength measures of the knee extensors and flexors, and the shoulder internal and external rotators on two different Humac NORM isokinetic dynamometers, which were situated at two different centers. The knee extensors and flexors were tested concentrically at 60° and 180°/s, and eccentrically at 60° s. Concentric strength of the shoulder internal and external rotators, and eccentric strength of the external rotators were measured at 60° and 120°/s. We calculated intraclass correlation coefficients (ICCs), standard error of measurement, standard error of measurement expressed as a %, and the smallest detectable change to determine reliability and measurement error. ICCs for the knee tests ranged from 0.74 to 0.89, whereas ICC values for the shoulder tests ranged from 0.72 to 0.94. Measurement error was highest for the concentric test of the knee extensors and lowest for the concentric test of shoulder external rotators.}, } @article {pmid29321057, year = {2018}, author = {Yildiz, S and Mazel-Sanchez, B and Kandasamy, M and Manicassamy, B and Schmolke, M}, title = {Influenza A virus infection impacts systemic microbiota dynamics and causes quantitative enteric dysbiosis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {9}, pmid = {29321057}, issn = {2049-2618}, support = {R01 AI123359/AI/NIAID NIH HHS/United States ; n/a//Fondation Ernst et Lucie Schmidheiny/International ; AI12335//National Institute of Allergy and Infectious Diseases/International ; R00 AI095320/AI/NIAID NIH HHS/United States ; AI095320//National Institute of Allergy and Infectious Diseases/International ; SNF310030_155949//Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung/International ; n/a//Foundation Novartis Consumer Health/International ; K99 AI095320/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Disease Models, Animal ; Dysbiosis/microbiology ; Female ; Gastrointestinal Microbiome ; Influenza A virus/pathogenicity ; Mice ; Orthomyxoviridae Infections/*microbiology ; Paneth Cells/*microbiology ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Microbiota integrity is essential for a growing number of physiological processes. Consequently, disruption of microbiota homeostasis correlates with a variety of pathological states. Importantly, commensal microbiota provide a shield against invading bacterial pathogens, probably by direct competition. The impact of viral infections on host microbiota composition and dynamics is poorly understood. Influenza A viruses (IAV) are common respiratory pathogens causing acute infections. Here, we show dynamic changes in respiratory and intestinal microbiota over the course of a sublethal IAV infection in a mouse model.

RESULTS: Using a combination of 16S rRNA gene-specific next generation sequencing and qPCR as well as culturing of bacterial organ content, we found body site-specific and transient microbiota responses. In the lower respiratory tract, we observed only minor qualitative changes in microbiota composition. No quantitative impact on bacterial colonization after IAV infection was detectable, despite a robust antimicrobial host response and increased sensitivity to bacterial super infection. In contrast, in the intestine, IAV induced robust depletion of bacterial content, disruption of mucus layer integrity, and higher levels of antimicrobial peptides in Paneth cells. As a functional consequence of IAV-mediated microbiota depletion, we demonstrated that the small intestine is rendered more susceptible to bacterial pathogen invasion, in a Salmonella typhimurium super infection model.

CONCLUSION: We show for the first time the consequences of IAV infection for lower respiratory tract and intestinal microbiobiota in a qualitative and quantitative fashion. The discrepancy of relative 16S rRNA gene next-generation sequencing (NGS) and normalized 16S rRNA gene-specific qPCR stresses the importance of combining qualitative and quantitative approaches to correctly analyze composition of organ associated microbial communities. The transiently induced dysbiosis underlines the overall stability of microbial communities to effects of acute infection. However, during a short-time window, specific ecological niches might lose their microbiota shield and remain vulnerable to bacterial invasion.}, } @article {pmid29321038, year = {2018}, author = {Cole, AM and Pflugeisen, B and Schwartz, MR and Miller, SC}, title = {Cross sectional study to assess the accuracy of electronic health record data to identify patients in need of lung cancer screening.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {14}, pmid = {29321038}, issn = {1756-0500}, support = {UL1 RR025014/RR/NCRR NIH HHS/United States ; UL1 TR000423/TR/NCATS NIH HHS/United States ; UL1 TR002319/TR/NCATS NIH HHS/United States ; UL1TR000423//National Center for Advancing Translational Sciences/ ; }, mesh = {Aged ; Aged, 80 and over ; Cross-Sectional Studies ; Early Detection of Cancer/*standards ; *Electronic Health Records ; Female ; Humans ; Lung Neoplasms/*diagnosis/diagnostic imaging ; Male ; Middle Aged ; Predictive Value of Tests ; Self Report/*standards ; Sensitivity and Specificity ; *Smoking ; }, abstract = {OBJECTIVE: Lung cancer is the leading cause of cancer death in the United States [Siegel et al. in CA Cancer J Clin 66:7-30, 1]. However, evidence from clinical trials indicates that annual low-dose computed tomography screening reduces lung cancer mortality [Humphrey et al. in Ann Intern Med 159:411-420, 2]. The objective of this study is to report results of a study designed to assess the sensitivity, specificity, and positive and negative predictive value of an electronic health record (EHR) query in comparison to patient self-report, to identify patients who may benefit from lung cancer screening. Cross sectional study comparing patient self report to EHR derived assessment of tobacco status and need for lung cancer screening. We invited 200 current or former smokers, ages 55-80 to complete a brief paper survey. 26 responded and 24 were included in the analysis.

RESULTS: For 30% of respondents, there was not adequate EHR data to make a lung cancer screening determination. Compared to patient self-report, EHR derived data has a 67% sensitivity and 82% specificity for identifying patients that meet criteria for lung cancer screening. While the degree of accuracy may be insufficient to make a final lung cancer screening determination, EHR data may be useful in prompting clinicians to initiate conversations with patients in regards to lung cancer screening.}, } @article {pmid29321020, year = {2018}, author = {Wang, Z and Arat, S and Magid-Slav, M and Brown, JR}, title = {Meta-analysis of human gene expression in response to Mycobacterium tuberculosis infection reveals potential therapeutic targets.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {3}, pmid = {29321020}, issn = {1752-0509}, abstract = {BACKGROUND: With the global emergence of multi-drug resistant strains of Mycobacterium tuberculosis, new strategies to treat tuberculosis are urgently needed such as therapeutics targeting potential human host factors.

RESULTS: Here we performed a statistical meta-analysis of human gene expression in response to both latent and active pulmonary tuberculosis infections from nine published datasets. We found 1655 genes that were significantly differentially expressed during active tuberculosis infection. In contrast, no gene was significant for latent tuberculosis. Pathway enrichment analysis identified 90 significant canonical human pathways, including several pathways more commonly related to non-infectious diseases such as the LRRK2 pathway in Parkinson's disease, and PD-1/PD-L1 signaling pathway important for new immuno-oncology therapies. The analysis of human genome-wide association studies datasets revealed tuberculosis-associated genetic variants proximal to several genes in major histocompatibility complex for antigen presentation. We propose several new targets and drug-repurposing opportunities including intravenous immunoglobulin, ion-channel blockers and cancer immuno-therapeutics for development as combination therapeutics with anti-mycobacterial agents.

CONCLUSIONS: Our meta-analysis provides novel insights into host genes and pathways important for tuberculosis and brings forth potential drug repurposing opportunities for host-directed therapies.}, } @article {pmid29321003, year = {2018}, author = {Komseli, ES and Pateras, IS and Krejsgaard, T and Stawiski, K and Rizou, SV and Polyzos, A and Roumelioti, FM and Chiourea, M and Mourkioti, I and Paparouna, E and Zampetidis, CP and Gumeni, S and Trougakos, IP and Pefani, DE and O'Neill, E and Gagos, S and Eliopoulos, AG and Fendler, W and Chowdhury, D and Bartek, J and Gorgoulis, VG}, title = {A prototypical non-malignant epithelial model to study genome dynamics and concurrently monitor micro-RNAs and proteins in situ during oncogene-induced senescence.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {37}, pmid = {29321003}, issn = {1471-2164}, support = {722729//Horizon 2020 Framework Programme/International ; DFF-4092-00122//Sapera Aude Talent Grant/International ; 722729//Horizon 2020/International ; 3081//National Scholarships Foundation-Siemens Aristeia Fellowship/International ; }, mesh = {Carcinogenesis ; Cell Cycle Proteins/metabolism ; Cells, Cultured ; Cellular Senescence/*genetics ; Epithelial Cells/metabolism ; Gene Expression Profiling ; Genome ; Humans ; MicroRNAs/metabolism ; Neoplasms, Glandular and Epithelial/*genetics/pathology/ultrastructure ; Nuclear Proteins/metabolism ; *Oncogenes ; Proteins/metabolism ; }, abstract = {BACKGROUND: Senescence is a fundamental biological process implicated in various pathologies, including cancer. Regarding carcinogenesis, senescence signifies, at least in its initial phases, an anti-tumor response that needs to be circumvented for cancer to progress. Micro-RNAs, a subclass of regulatory, non-coding RNAs, participate in senescence regulation. At the subcellular level micro-RNAs, similar to proteins, have been shown to traffic between organelles influencing cellular behavior. The differential function of micro-RNAs relative to their subcellular localization and their role in senescence biology raises concurrent in situ analysis of coding and non-coding gene products in senescent cells as a necessity. However, technical challenges have rendered in situ co-detection unfeasible until now.

METHODS: In the present report we describe a methodology that bypasses these technical limitations achieving for the first time simultaneous detection of both a micro-RNA and a protein in the biological context of cellular senescence, utilizing the new commercially available SenTraGorTM compound. The method was applied in a prototypical human non-malignant epithelial model of oncogene-induced senescence that we generated for the purposes of the study. For the characterization of this novel system, we applied a wide range of cellular and molecular techniques, as well as high-throughput analysis of the transcriptome and micro-RNAs.

RESULTS: This experimental setting has three advantages that are presented and discussed: i) it covers a "gap" in the molecular carcinogenesis field, as almost all corresponding in vitro models are fibroblast-based, even though the majority of neoplasms have epithelial origin, ii) it recapitulates the precancerous and cancerous phases of epithelial tumorigenesis within a short time frame under the light of natural selection and iii) it uses as an oncogenic signal, the replication licensing factor CDC6, implicated in both DNA replication and transcription when over-expressed, a characteristic that can be exploited to monitor RNA dynamics.

CONCLUSIONS: Consequently, we demonstrate that our model is optimal for studying the molecular basis of epithelial carcinogenesis shedding light on the tumor-initiating events. The latter may reveal novel molecular targets with clinical benefit. Besides, since this method can be incorporated in a wide range of low, medium or high-throughput image-based approaches, we expect it to be broadly applicable.}, } @article {pmid29320989, year = {2018}, author = {Rile, N and Liu, Z and Gao, L and Qi, J and Zhao, M and Xie, Y and Su, R and Zhang, Y and Wang, R and Li, J and Xiao, H and Li, J}, title = {Expression of Vimentin in hair follicle growth cycle of inner Mongolian Cashmere goats.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {38}, pmid = {29320989}, issn = {1471-2164}, support = {2013AA102506//National "863" Project/International ; 31360537, 31660640//National Natural Science Foundation of China/International ; 2017MS0356//Natural Science Foundation of Inner Mongolia/International ; 2016ZD02//Major projects of Inner Mongolia Natural Science Foundation/International ; }, mesh = {Amino Acid Sequence ; Animals ; China ; Female ; Gene Expression ; Goats/genetics/*growth & development/metabolism ; Hair Follicle/*growth & development/metabolism ; RNA, Messenger/chemistry ; Sequence Alignment ; Sequence Analysis, RNA ; Vimentin/chemistry/genetics/*metabolism ; }, abstract = {BACKGROUND: The growth of Inner Mongolian Cashmere goat skin hair follicle exhibits a periodic growth pattern. The hair growth cycle is distinguished as telogen, anagen, and catagen stages. The role of vimentin in the growth process of hair follicles is evident. To elucidate the mechanism underlying the vimentin activity in the growth cycle of hair follicles, transcriptome sequencing and liquid chromatography-tandem mass spectrometry were used to obtain the nucleic acid and amino acid sequences of VIIM gene and vimentin. The amino acid and nucleic acid sequences were analyzed by comparison. Real-time quantitative PCR, Western blot, and immunohistochemistry analyzed the expression level and sites of vimentin in the three growth stages of the Inner Mongolia Cashmere goat skin samples.

RESULTS: VIM gene cDNA, obtained by transcriptome sequencing, was aligned against that of the Capra hircus VIM gene. The amino acid sequence of vimentin revealed a high similarity rate across other species. The expressions of both VIM gene and vimentin were highest during the growth period and lowest in the rest period. Furthermore, vimentin was primarily expressed in the outer root sheath of the hair follicle as assessed by staining.

CONCLUSIONS: The sequences of the gene and protein are similar to that of other species and identical to Capra hircus. However, the expression of VIM and vimentin was proportional to that of the growth of hair follicles. And vimentin expressed only in the outer root sheath of hair follicles. Thus, vimentin was speculated to participate in the regulation of the hair follicle growth cycle by affecting the outer root sheath.}, } @article {pmid29320985, year = {2018}, author = {Chen, J and Burke, JJ and Xin, Z}, title = {Chlorophyll fluorescence analysis revealed essential roles of FtsH11 protease in regulation of the adaptive responses of photosynthetic systems to high temperature.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {11}, pmid = {29320985}, issn = {1471-2229}, support = {US-422-09//United States - Israel Binational Agricultural Research and Development Fund/International ; }, mesh = {Arabidopsis/*genetics/metabolism ; Arabidopsis Proteins/*genetics/metabolism ; Chlorophyll/*metabolism ; Fluorescence ; *Hot Temperature ; *Light ; Metalloproteases/*genetics/metabolism ; Mutation ; Photosynthesis/genetics/*physiology ; }, abstract = {BACKGROUND: Photosynthetic systems are known to be sensitive to high temperature stress. To maintain a relatively "normal" level of photosynthetic activities, plants employ a variety of adaptive mechanisms in response to environmental temperature fluctuations. Previously, we reported that the chloroplast-targeted AtFtsH11 protease played an essential role for Arabidopsis plants to survive at high temperatures and to maintain normal photosynthetic efficiency at moderately elevated temperature. To investigate the factors contributing to the photosynthetic changes in FtsH11 mutant, we performed detailed chlorophyll fluorescence analyses of dark-adapted mutant plants and compared them to Col-0 WT plants under normal, two moderate high temperatures, and a high light conditions.

RESULTS: We found that mutation of FtsH11 gene caused significant decreases in photosynthetic efficiency of photosystems when environmental temperature raised above optimal. Under moderately high temperatures, the FtsH11 mutant showed significant 1) decreases in electron transfer rates of photosystem II (PSII) and photosystem I (PSI), 2) decreases in photosynthetic capabilities of PSII and PSI, 3) increases in non-photochemical quenching, and a host of other chlorophyll fluorescence parameter changes. We also found that the degrees of these negative changes for utilizing the absorbed light energy for photosynthesis in FtsH11 mutant were correlated with the level and duration of the heat treatments. For plants grown under normal temperature and subjected to the high light treatment, no significant difference in chlorophyll fluorescence parameters was found between the FtsH11 mutant and Col-0 WT plants.

CONCLUSIONS: The results of this study show that AtFtsH11 is essential for normal photosynthetic function under moderately elevated temperatures. The results also suggest that the network mediated by AtFtsH11 protease plays critical roles for maintaining the thermostability and possibly structural integrity of both photosystems under elevated temperatures. Elucidating the underlying mechanisms of FtsH11 protease in photosystems may lead to improvement of photosynthetic efficiency under heat stress conditions, hence, plant productivity.}, } @article {pmid29320982, year = {2018}, author = {Wei, K and Chen, H}, title = {Global identification, structural analysis and expression characterization of cytochrome P450 monooxygenase superfamily in rice.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {35}, pmid = {29320982}, issn = {1471-2164}, support = {Grant No.2015I0006//The project was supported by the Science and Technology Cooperation Project of Fujian Province, China/International ; }, mesh = {Cytochrome P-450 Enzyme System/chemistry/classification/*genetics/metabolism ; Droughts ; Evolution, Molecular ; Exons ; Gene Duplication ; Gene Expression Profiling ; Introns ; MicroRNAs/metabolism ; *Multigene Family ; Oryza/embryology/*enzymology/genetics/growth & development ; Phylogeny ; Plant Proteins/chemistry/*genetics/metabolism ; Regulatory Elements, Transcriptional ; Sequence Analysis, Protein ; Structural Homology, Protein ; }, abstract = {BACKGROUND: The cytochrome P450 monooxygenases (CYP450, CYP, P450) catalyze numerous monooxygenation/hydroxylation reactions in biochemical pathways. Although CYP superfamily has been systematically studied in a few species, the genome-scale research about it in rice has not been done.

RESULTS: In this study, a total of 355 CYPs encoded by 326 genes were identified in japonica genome. The OsCYP genes are classified into 10 clans including 45 families according to phylogenetic analysis. More than half of the genes are distributed in 53 tandem duplicated gene clusters. Intron-exon structure of OsCYPs exhibits highly conserved and specificity within a family, and divergences of duplicate genes in gene structure result in non-functionalization, neo-functionalization or sub-functionalization. Selection pressure analysis showed that rice CYPs are under purifying selection. The microarray data analysis shows that some genes are tissue-specific expression, such as OsCYP710A5 and OsCYP71X14 in endosperm, OsCYP99A3 and OsCYP78A16 in root and OsCYP93G2 and OsCYP97D7 in leaf. Analysis of RNA-seq data derived from rice leaf developmental gradient indicates that some OsCYPs exhibit zone-specific expression patterns. OsCYP87C2, OsCYP96B5, OsCYP96B8 and OsCYP84A5 were specifically expressed in leaf base and transitional zone. The transcripts of lineages II and IV-1 members were highly abundant in maturing zone. Eighty three OsCYPs are differentially expressed in response to drought stress, of which OsCYP51G3, OsCYP709C9, OsCYP709C5, OsCYP81A6, OsCYP72A18 and OsCYP704A5 are strongly induced and OsCYP78A16, OsCYP89C9 and OsCYP704A5 are down-regulated significantly, and some of the results were validated by qPCR. And 23 up-regulated and 17 down-regulated genes are specific to Osbhlh148 mutation under drought stress. Compared to those in wild type, the changes in transcript levels of several genes are slight in the mutant, such as OsCYP51G3, OsCYP94C2, OsCYP709C9 and OsCYP709C5.

CONCLUSION: The whole-genomic analysis of rice P450 superfamily provides a clue to understanding biological function of OsCYPs in development regulation and drought stress response, and is helpful to rice molecular breeding.}, } @article {pmid29320481, year = {2018}, author = {Bi, Y and Mann, E and Whitfield, C and Zimmer, J}, title = {Architecture of a channel-forming O-antigen polysaccharide ABC transporter.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {361-365}, pmid = {29320481}, issn = {1476-4687}, support = {P30 EB009998/EB/NIBIB NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 GM110143/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; }, mesh = {ATP-Binding Cassette Transporters/*chemistry/genetics/metabolism ; Bacterial Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Escherichia coli/chemistry ; Hydrolysis ; Models, Molecular ; O Antigens/*metabolism ; Polysaccharides/metabolism ; Protein Domains ; Structure-Activity Relationship ; }, abstract = {O-antigens are cell surface polysaccharides of many Gram-negative pathogens that aid in escaping innate immune responses. A widespread O-antigen biosynthesis mechanism involves the synthesis of the lipid-anchored polymer on the cytosolic face of the inner membrane, followed by transport to the periplasmic side where it is ligated to the lipid A core to complete a lipopolysaccharide molecule. In this pathway, transport to the periplasm is mediated by an ATP-binding cassette (ABC) transporter, called Wzm-Wzt. Here we present the crystal structure of the Wzm-Wzt homologue from Aquifex aeolicus in an open conformation. The transporter forms a transmembrane channel that is sufficiently wide to accommodate a linear polysaccharide. Its nucleotide-binding domain and a periplasmic extension form 'gate helices' at the cytosolic and periplasmic membrane interfaces that probably serve as substrate entry and exit points. Site-directed mutagenesis of the gates impairs in vivo O-antigen secretion in the Escherichia coli prototype. Combined with a closed structure of the isolated nucleotide-binding domains, our structural and functional analyses suggest a processive O-antigen translocation mechanism, which stands in contrast to the classical alternating access mechanism of ABC transporters.}, } @article {pmid29320480, year = {2018}, author = {Sulli, G and Rommel, A and Wang, X and Kolar, MJ and Puca, F and Saghatelian, A and Plikus, MV and Verma, IM and Panda, S}, title = {Pharmacological activation of REV-ERBs is lethal in cancer and oncogene-induced senescence.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {351-355}, pmid = {29320480}, issn = {1476-4687}, support = {R01 AR067273/AR/NIAMS NIH HHS/United States ; F30 DK112604/DK/NIDDK NIH HHS/United States ; R01 AR069653/AR/NIAMS NIH HHS/United States ; T32 GM007198/GM/NIGMS NIH HHS/United States ; P30 CA014195/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/drug effects ; Autophagy/drug effects ; Cell Line, Tumor ; Cell Survival/drug effects ; Circadian Clocks/genetics/physiology ; Female ; GTP Phosphohydrolases/genetics/metabolism ; Glioblastoma/drug therapy/pathology ; Humans ; Lipogenesis/drug effects ; Male ; Membrane Proteins/genetics/metabolism ; Mice, Inbred C57BL ; Neoplasms/*drug therapy/genetics/*pathology ; Nevus/drug therapy/pathology ; Nuclear Receptor Subfamily 1, Group D, Member 1/*agonists/metabolism ; Oncogenes/*genetics ; Pyrrolidines/pharmacology ; Signal Transduction/drug effects ; Thiophenes/pharmacology ; }, abstract = {The circadian clock imposes daily rhythms in cell proliferation, metabolism, inflammation and DNA damage response. Perturbations of these processes are hallmarks of cancer and chronic circadian rhythm disruption predisposes individuals to tumour development. This raises the hypothesis that pharmacological modulation of the circadian machinery may be an effective therapeutic strategy for combating cancer. REV-ERBs, the nuclear hormone receptors REV-ERBα (also known as NR1D1) and REV-ERBβ (also known as NR1D2), are essential components of the circadian clock. Here we show that two agonists of REV-ERBs-SR9009 and SR9011-are specifically lethal to cancer cells and oncogene-induced senescent cells, including melanocytic naevi, and have no effect on the viability of normal cells or tissues. The anticancer activity of SR9009 and SR9011 affects a number of oncogenic drivers (such as HRAS, BRAF, PIK3CA and others) and persists in the absence of p53 and under hypoxic conditions. The regulation of autophagy and de novo lipogenesis by SR9009 and SR9011 has a critical role in evoking an apoptotic response in malignant cells. Notably, the selective anticancer properties of these REV-ERB agonists impair glioblastoma growth in vivo and improve survival without causing overt toxicity in mice. These results indicate that pharmacological modulation of circadian regulators is an effective antitumour strategy, identifying a class of anticancer agents with a wide therapeutic window. We propose that REV-ERB agonists are inhibitors of autophagy and de novo lipogenesis, with selective activity towards malignant and benign neoplasms.}, } @article {pmid29320479, year = {2018}, author = {Gibeaux, R and Acker, R and Kitaoka, M and Georgiou, G and van Kruijsbergen, I and Ford, B and Marcotte, EM and Nomura, DK and Kwon, T and Veenstra, GJC and Heald, R}, title = {Paternal chromosome loss and metabolic crisis contribute to hybrid inviability in Xenopus.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {337-341}, pmid = {29320479}, issn = {1476-4687}, support = {DP1 GM106408/GM/NIGMS NIH HHS/United States ; R35 GM118183/GM/NIGMS NIH HHS/United States ; T32 GM007232/GM/NIGMS NIH HHS/United States ; R01 CA172667/CA/NCI NIH HHS/United States ; 4T32GM007232-40/NH/NIH HHS/United States ; R01 HD069344/HD/NICHD NIH HHS/United States ; S10 OD018174/OD/NIH HHS/United States ; R35 GM122480/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chromosome Segregation ; Chromosomes/*genetics/metabolism ; Cytoplasm/genetics/metabolism ; Embryo Loss/veterinary ; Evolution, Molecular ; Female ; Genetic Speciation ; *Hybridization, Genetic ; Male ; Mitosis ; Paternal Inheritance/*genetics ; Xenopus/*genetics/*metabolism ; Xenopus laevis/genetics ; }, abstract = {Hybridization of eggs and sperm from closely related species can give rise to genetic diversity, or can lead to embryo inviability owing to incompatibility. Although central to evolution, the cellular and molecular mechanisms underlying post-zygotic barriers that drive reproductive isolation and speciation remain largely unknown. Species of the African clawed frog Xenopus provide an ideal system to study hybridization and genome evolution. Xenopus laevis is an allotetraploid with 36 chromosomes that arose through interspecific hybridization of diploid progenitors, whereas Xenopus tropicalis is a diploid with 20 chromosomes that diverged from a common ancestor approximately 48 million years ago. Differences in genome size between the two species are accompanied by organism size differences, and size scaling of the egg and subcellular structures such as nuclei and spindles formed in egg extracts. Nevertheless, early development transcriptional programs, gene expression patterns, and protein sequences are generally conserved. Whereas the hybrid produced when X. laevis eggs are fertilized by X. tropicalis sperm is viable, the reverse hybrid dies before gastrulation. Here we apply cell biological tools and high-throughput methods to study the mechanisms underlying hybrid inviability. We reveal that two specific X. laevis chromosomes are incompatible with the X. tropicalis cytoplasm and are mis-segregated during mitosis, leading to unbalanced gene expression at the maternal to zygotic transition, followed by cell-autonomous catastrophic embryo death. These results reveal a cellular mechanism underlying hybrid incompatibility that is driven by genome evolution and contributes to the process by which biological populations become distinct species.}, } @article {pmid29320478, year = {2018}, author = {Smakowska-Luzan, E and Mott, GA and Parys, K and Stegmann, M and Howton, TC and Layeghifard, M and Neuhold, J and Lehner, A and Kong, J and Grünwald, K and Weinberger, N and Satbhai, SB and Mayer, D and Busch, W and Madalinski, M and Stolt-Bergner, P and Provart, NJ and Mukhtar, MS and Zipfel, C and Desveaux, D and Guttman, DS and Belkhadir, Y}, title = {An extracellular network of Arabidopsis leucine-rich repeat receptor kinases.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {342-346}, doi = {10.1038/nature25184}, pmid = {29320478}, issn = {1476-4687}, mesh = {Arabidopsis/cytology/*enzymology/immunology/microbiology ; Arabidopsis Proteins/*chemistry/*metabolism ; Leucine/*metabolism ; Protein Binding ; Protein Domains ; Protein Kinases/*chemistry/*metabolism ; Protein-Serine-Threonine Kinases/chemistry/metabolism ; Receptors, Cell Surface/chemistry/metabolism ; Reproducibility of Results ; Signal Transduction ; }, abstract = {The cells of multicellular organisms receive extracellular signals using surface receptors. The extracellular domains (ECDs) of cell surface receptors function as interaction platforms, and as regulatory modules of receptor activation. Understanding how interactions between ECDs produce signal-competent receptor complexes is challenging because of their low biochemical tractability. In plants, the discovery of ECD interactions is complicated by the massive expansion of receptor families, which creates tremendous potential for changeover in receptor interactions. The largest of these families in Arabidopsis thaliana consists of 225 evolutionarily related leucine-rich repeat receptor kinases (LRR-RKs), which function in the sensing of microorganisms, cell expansion, stomata development and stem-cell maintenance. Although the principles that govern LRR-RK signalling activation are emerging, the systems-level organization of this family of proteins is unknown. Here, to address this, we investigated 40,000 potential ECD interactions using a sensitized high-throughput interaction assay, and produced an LRR-based cell surface interaction network (CSILRR) that consists of 567 interactions. To demonstrate the power of CSILRR for detecting biologically relevant interactions, we predicted and validated the functions of uncharacterized LRR-RKs in plant growth and immunity. In addition, we show that CSILRR operates as a unified regulatory network in which the LRR-RKs most crucial for its overall structure are required to prevent the aberrant signalling of receptors that are several network-steps away. Thus, plants have evolved LRR-RK networks to process extracellular signals into carefully balanced responses.}, } @article {pmid29320477, year = {2018}, author = {Weiss, DJ and Nelson, A and Gibson, HS and Temperley, W and Peedell, S and Lieber, A and Hancher, M and Poyart, E and Belchior, S and Fullman, N and Mappin, B and Dalrymple, U and Rozier, J and Lucas, TCD and Howes, RE and Tusting, LS and Kang, SY and Cameron, E and Bisanzio, D and Battle, KE and Bhatt, S and Gething, PW}, title = {A global map of travel time to cities to assess inequalities in accessibility in 2015.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {333-336}, doi = {10.1038/nature25181}, pmid = {29320477}, issn = {1476-4687}, support = {MR/K00669X/1//Medical Research Council/United Kingdom ; }, mesh = {*Cities/statistics & numerical data ; Educational Status ; Geography ; Health Status ; Healthcare Disparities/statistics & numerical data ; Humans ; *Internationality ; *Maps as Topic ; *Socioeconomic Factors ; *Spatio-Temporal Analysis ; Time Factors ; *Travel/statistics & numerical data ; Urban Population/statistics & numerical data ; }, abstract = {The economic and man-made resources that sustain human wellbeing are not distributed evenly across the world, but are instead heavily concentrated in cities. Poor access to opportunities and services offered by urban centres (a function of distance, transport infrastructure, and the spatial distribution of cities) is a major barrier to improved livelihoods and overall development. Advancing accessibility worldwide underpins the equity agenda of 'leaving no one behind' established by the Sustainable Development Goals of the United Nations. This has renewed international efforts to accurately measure accessibility and generate a metric that can inform the design and implementation of development policies. The only previous attempt to reliably map accessibility worldwide, which was published nearly a decade ago, predated the baseline for the Sustainable Development Goals and excluded the recent expansion in infrastructure networks, particularly in lower-resource settings. In parallel, new data sources provided by Open Street Map and Google now capture transportation networks with unprecedented detail and precision. Here we develop and validate a map that quantifies travel time to cities for 2015 at a spatial resolution of approximately one by one kilometre by integrating ten global-scale surfaces that characterize factors affecting human movement rates and 13,840 high-density urban centres within an established geospatial-modelling framework. Our results highlight disparities in accessibility relative to wealth as 50.9% of individuals living in low-income settings (concentrated in sub-Saharan Africa) reside within an hour of a city compared to 90.7% of individuals in high-income settings. By further triangulating this map against socioeconomic datasets, we demonstrate how access to urban centres stratifies the economic, educational, and health status of humanity.}, } @article {pmid29320476, year = {2018}, author = {Milner, JJ and Toma, C and Yu, B and Zhang, K and Omilusik, K and Phan, AT and Wang, D and Getzler, AJ and Nguyen, T and Crotty, S and Wang, W and Pipkin, ME and Goldrath, AW}, title = {Erratum: Runx3 programs CD8+ T cell residency in non-lymphoid tissues and tumours.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {392}, pmid = {29320476}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24993.}, } @article {pmid29320475, year = {2018}, author = {Daskin, JH and Pringle, RM}, title = {Warfare and wildlife declines in Africa's protected areas.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {328-332}, doi = {10.1038/nature25194}, pmid = {29320475}, issn = {1476-4687}, mesh = {Africa ; Animals ; *Animals, Wild ; *Biodiversity ; *Conservation of Natural Resources ; Herbivory ; Mammals/physiology ; Population Dynamics ; *Warfare and Armed Conflicts ; Wilderness ; }, abstract = {Large-mammal populations are ecological linchpins, and their worldwide decline and extinction disrupts many ecosystem functions and services. Reversal of this trend will require an understanding of the determinants of population decline, to enable more accurate predictions of when and where collapses will occur and to guide the development of effective conservation and restoration policies. Many correlates of large-mammal declines are known, including low reproductive rates, overhunting, and habitat destruction. However, persistent uncertainty about the effects of one widespread factor-armed conflict-complicates conservation-planning and priority-setting efforts. Case studies have revealed that conflict can have either positive or negative local impacts on wildlife, but the direction and magnitude of its net effect over large spatiotemporal scales have not previously been quantified. Here we show that conflict frequency predicts the occurrence and severity of population declines among wild large herbivores in African protected areas from 1946 to 2010. Conflict was extensive during this period, occurring in 71% of protected areas, and conflict frequency was the single most important predictor of wildlife population trends among the variables that we analysed. Population trajectories were stable in peacetime, fell significantly below replacement with only slight increases in conflict frequency (one conflict-year per two-to-five decades), and were almost invariably negative in high-conflict sites, both in the full 65-year dataset and in an analysis restricted to recent decades (1989-2010). Yet total population collapse was infrequent, indicating that war-torn faunas can often recover. Human population density was also correlated (positively) with wildlife population trajectories in recent years; however, we found no significant effect, in either timespan, of species body mass, protected-area size, conflict intensity (human fatalities), drought frequency, presence of extractable mineral resources, or various metrics of development and governance. Our results suggest that sustained conservation activity in conflict zones-and rapid interventions following ceasefires-may help to save many at-risk populations and species.}, } @article {pmid29320474, year = {2018}, author = {Eroglu, Z and Zaretsky, JM and Hu-Lieskovan, S and Kim, DW and Algazi, A and Johnson, DB and Liniker, E and Ben Kong, and Munhoz, R and Rapisuwon, S and Gherardini, PF and Chmielowski, B and Wang, X and Shintaku, IP and Wei, C and Sosman, JA and Joseph, RW and Postow, MA and Carlino, MS and Hwu, WJ and Scolyer, RA and Messina, J and Cochran, AJ and Long, GV and Ribas, A}, title = {High response rate to PD-1 blockade in desmoplastic melanomas.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {347-350}, pmid = {29320474}, issn = {1476-4687}, support = {T32 GM008042/GM/NIGMS NIH HHS/United States ; R35 CA197633/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; P30 CA076292/CA/NCI NIH HHS/United States ; P01 CA168585/CA/NCI NIH HHS/United States ; P50 CA168536/CA/NCI NIH HHS/United States ; }, mesh = {B7-H1 Antigen/antagonists & inhibitors/metabolism ; Biopsy ; CD8-Positive T-Lymphocytes/cytology/immunology ; Cell Cycle Checkpoints ; Humans ; *Immunotherapy ; Melanoma/genetics/*immunology/metabolism/*therapy ; Mutation/genetics ; Neurofibromin 1/genetics ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors/metabolism ; Retrospective Studies ; }, abstract = {Desmoplastic melanoma is a rare subtype of melanoma characterized by dense fibrous stroma, resistance to chemotherapy and a lack of actionable driver mutations, and is highly associated with ultraviolet light-induced DNA damage. We analysed sixty patients with advanced desmoplastic melanoma who had been treated with antibodies to block programmed cell death 1 (PD-1) or PD-1 ligand (PD-L1). Objective tumour responses were observed in forty-two of the sixty patients (70%; 95% confidence interval 57-81%), including nineteen patients (32%) with a complete response. Whole-exome sequencing revealed a high mutational load and frequent NF1 mutations (fourteen out of seventeen cases) in these tumours. Immunohistochemistry analysis from nineteen desmoplastic melanomas and thirteen non-desmoplastic melanomas revealed a higher percentage of PD-L1-positive cells in the tumour parenchyma in desmoplastic melanomas (P = 0.04); these cells were highly associated with increased CD8 density and PD-L1 expression in the tumour invasive margin. Therefore, patients with advanced desmoplastic melanoma derive substantial clinical benefit from PD-1 or PD-L1 immune checkpoint blockade therapy, even though desmoplastic melanoma is defined by its dense desmoplastic fibrous stroma. The benefit is likely to result from the high mutational burden and a frequent pre-existing adaptive immune response limited by PD-L1 expression.}, } @article {pmid29320473, year = {2018}, author = {Yang, Z and Wei, J and Sobolev, YI and Grzybowski, BA}, title = {Systems of mechanized and reactive droplets powered by multi-responsive surfactants.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {313-318}, doi = {10.1038/nature25137}, pmid = {29320473}, issn = {1476-4687}, abstract = {Although 'active' surfactants, which are responsive to individual external stimuli such as temperature, electric or magnetic fields, light, redox processes or chemical agents, are well known, it would be interesting to combine several of these properties within one surfactant species. Such multi-responsive surfactants could provide ways of manipulating individual droplets and possibly assembling them into larger systems of dynamic reactors. Here we describe surfactants based on functionalized nanoparticle dimers that combine all of these and several other characteristics. These surfactants and therefore the droplets that they cover are simultaneously addressable by magnetic, optical and electric fields. As a result, the surfactant-covered droplets can be assembled into various hierarchical structures, including dynamic ones, in which light powers the rapid rotation of the droplets. Such rotating droplets can transfer mechanical torques to their non-nearest neighbours, thus acting like systems of mechanical gears. Furthermore, droplets of different types can be merged by applying electric fields and, owing to interfacial jamming, can form complex, non-spherical, 'patchy' structures with different surface regions covered with different surfactants. In systems of droplets that carry different chemicals, combinations of multiple stimuli can be used to control the orientations of the droplets, inter-droplet transport, mixing of contents and, ultimately, sequences of chemical reactions. Overall, the multi-responsive active surfactants that we describe provide an unprecedented level of flexibility with which liquid droplets can be manipulated, assembled and reacted.}, } @article {pmid29319883, year = {2018}, author = {McLean, BS and Helgen, KM and Goodwin, HT and Cook, JA}, title = {Trait-specific processes of convergence and conservatism shape ecomorphological evolution in ground-dwelling squirrels.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {473-489}, doi = {10.1111/evo.13422}, pmid = {29319883}, issn = {1558-5646}, abstract = {Our understanding of mechanisms operating over deep timescales to shape phenotypic diversity often hinges on linking variation in one or few trait(s) to specific evolutionary processes. When distinct processes are capable of similar phenotypic signatures, however, identifying these drivers is difficult. We explored ecomorphological evolution across a radiation of ground-dwelling squirrels whose history includes convergence and constraint, two processes that can yield similar signatures of standing phenotypic diversity. Using four ecologically relevant trait datasets (body size, cranial, mandibular, and molariform tooth shape), we compared and contrasted variation, covariation, and disparity patterns in a new phylogenetic framework. Strong correlations existed between body size and two skull traits (allometry) and among skull traits themselves (integration). Inferred evolutionary modes were also concordant across traits (Ornstein-Uhlenbeck with two adaptive regimes). However, despite these broad similarities, we found divergent dynamics on the macroevolutionary landscape, with phenotypic disparity being differentially shaped by convergence and conservatism. Such among-trait heterogeneity in process (but not always pattern) reiterates the mosaic nature of morphological evolution, and suggests ground squirrel evolution is poorly captured by single process descriptors. Our results also highlight how use of single traits can bias macroevolutionary inference, affirming the importance of broader trait-bases in understanding phenotypic evolutionary dynamics.}, } @article {pmid29319812, year = {2018}, author = {Inoue, J and Satoh, N}, title = {Deuterostome Genomics: Lineage-Specific Protein Expansions That Enabled Chordate Muscle Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {914-924}, pmid = {29319812}, issn = {1537-1719}, abstract = {Fish-like larvae were foundational to the chordate body plan, given the basal placement of free-living lancelets. That body plan probably made it possible for chordate ancestors to swim by beating a tail formed of notochord and bilateral paraxial muscles. In order to investigate the molecular genetic basis of the origin and evolution of paraxial muscle, we deduced the evolutionary histories of 16 contractile protein genes from paraxial muscle, based on genomic data from all five deuterostome lineages, using a newly developed orthology identification pipeline and a species tree. As a result, we found that more than twice as many orthologs of paraxial muscle genes are present in chordates, as in nonchordate deuterostomes (ambulacrarians). Orthologs of paraxial-type actin and troponin C genes are absent in ambulacrarians and most paraxial muscle protein isoforms diversified via gene duplications that occurred in each chordate lineage. Analyses of genes with known expression sites indicated that some isoforms were reutilized in specific muscles of nonvertebrate chordates via gene duplications. As orthologs of most paraxial muscle genes were present in ambulacrarians, in addition to expression patterns of related genes and functions of the two protein isoforms, regulatory mechanisms of muscle genes should also be considered in future studies of the origin of paraxial muscle.}, } @article {pmid29319806, year = {2018}, author = {Versluis, D and Nijsse, B and Naim, MA and Koehorst, JJ and Wiese, J and Imhoff, JF and Schaap, PJ and van Passel, MWJ and Smidt, H and Sipkema, D}, title = {Comparative Genomics Highlights Symbiotic Capacities and High Metabolic Flexibility of the Marine Genus Pseudovibrio.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {125-142}, pmid = {29319806}, issn = {1759-6653}, mesh = {Animals ; Drug Resistance, Bacterial ; Genome, Bacterial ; Genomics ; Multigene Family ; Porifera/*microbiology/physiology ; Quorum Sensing ; Rhodobacteraceae/*genetics/physiology ; Secondary Metabolism ; *Symbiosis ; }, abstract = {Pseudovibrio is a marine bacterial genus members of which are predominantly isolated from sessile marine animals, and particularly sponges. It has been hypothesized that Pseudovibrio spp. form mutualistic relationships with their hosts. Here, we studied Pseudovibrio phylogeny and genetic adaptations that may play a role in host colonization by comparative genomics of 31 Pseudovibrio strains, including 25 sponge isolates. All genomes were highly similar in terms of encoded core metabolic pathways, albeit with substantial differences in overall gene content. Based on gene composition, Pseudovibrio spp. clustered by geographic region, indicating geographic speciation. Furthermore, the fact that isolates from the Mediterranean Sea clustered by sponge species suggested host-specific adaptation or colonization. Genome analyses suggest that Pseudovibrio hongkongensis UST20140214-015BT is only distantly related to other Pseudovibrio spp., thereby challenging its status as typical Pseudovibrio member. All Pseudovibrio genomes were found to encode numerous proteins with SEL1 and tetratricopeptide repeats, which have been suggested to play a role in host colonization. For evasion of the host immune system, Pseudovibrio spp. may depend on type III, IV, and VI secretion systems that can inject effector molecules into eukaryotic cells. Furthermore, Pseudovibrio genomes carry on average seven secondary metabolite biosynthesis clusters, reinforcing the role of Pseudovibrio spp. as potential producers of novel bioactive compounds. Tropodithietic acid, bacteriocin, and terpene biosynthesis clusters were highly conserved within the genus, suggesting an essential role in survival, for example through growth inhibition of bacterial competitors. Taken together, these results support the hypothesis that Pseudovibrio spp. have mutualistic relations with sponges.}, } @article {pmid29319231, year = {2018}, author = {Venditti, M and Donizetti, A and Fiengo, M and Fasano, C and Santillo, A and Aniello, F and Minucci, S}, title = {Temporal and spatial expression of insulin-like peptide (insl5a and insl5b) paralog genes during the embryogenesis of Danio rerio.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {1}, pages = {33-40}, doi = {10.1002/jez.b.22787}, pmid = {29319231}, issn = {1552-5015}, mesh = {Amino Acid Sequence ; Animals ; Computational Biology ; Embryonic Development/*physiology ; Gene Expression Regulation, Developmental/*physiology ; Insulin ; Protein Isoforms ; Proteins ; RNA, Messenger/genetics/metabolism ; Zebrafish ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Relaxin (RLN) and insulin (INSL)-like peptides are member of the INSL/RLN superfamily, which are encoded by seven genes in humans and can activate the G-protein coupled receptor RXFP 1-4. These peptides evolved from a common ancestor, RLN3-like gene. Two rounds of whole genome duplication (WGD) in early vertebrate evolution, together with an additional WGD in the teleost lineage, caused an expansion of RLN genes set in the genome of Danio rerio. In particular, six RLN genes are present: a single copy of rln and insl3 genes, and two paralogs for the rln3 gene (rln3a and rln3b), and the insl5 gene (insl5a and insl5b). We have already reported the presence of rln3a and rln3b genes in the developing zebrafish brain, as well as the expression of rln gene in the developing zebrafish brain and extraneural territories, such as thyroid gland and pancreas. Here, we report for the first time the expression of the two parologs genes for insl5, insl5a, and insl5b in D. rerio embryonic development. The corresponding transcripts of both the paralogs are present in all embryonic stages analyzed by RT-qPCR. In situ hybridization analyses showed a restricted signal in intestinal cells and the pancreatic region at 72 hpf for insl5a, while at 96 hpf both genes are expressed in specific intestinal cells. Furthermore, in adult zebrafish intestine tissue, in situ hybridation experiments showed that insl5a transcript is specifically localized in the goblet cells, while insl5b transcript is in enteroendocrine cells. These data revealed a high degree of gene expression pattern conservation for such genes in vertebrate evolution.}, } @article {pmid29319173, year = {2018}, author = {Pérez-Escobar, OA and Cass, S and Dodsworth, S}, title = {Digest: Drivers of coral diversification in a major marine biodiversity hotspot.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {406-408}, doi = {10.1111/evo.13419}, pmid = {29319173}, issn = {1558-5646}, } @article {pmid29318754, year = {2018}, author = {Grieco, TM and Richman, JM}, title = {Coordination of bilateral tooth replacement in the juvenile gecko is continuous with in ovo patterning.}, journal = {Evolution & development}, volume = {20}, number = {2}, pages = {51-64}, pmid = {29318754}, issn = {1525-142X}, support = {F32 DE024948/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Body Patterning ; Dentition ; Jaw/*physiology ; Lizards/embryology/*growth & development ; Odontogenesis/*physiology ; Ovum/growth & development ; Tooth/embryology/*growth & development ; }, abstract = {We performed a test of how function impacts a genetically programmed process that continues into postnatal life. Using the dentition of the polyphyodont gecko as our model, tooth shedding was recorded longitudinally across the jaw. We compared two time periods: one in which teeth were patterned symmetrically in ovo and a later period when teeth were initiated post-hatching. By pairing shedding events on the right and left sides, we found the patterns of tooth loss are symmetrical and stable between periods, with only subtle deviations. Contralateral tooth positions shed within 3-4 days of each other in most animals (7/10). A minority of animals (3/10) had systematic tooth position shifts between right and left sides, likely due to changes in functional tooth number. Our results suggest that in addition to reproducible organogenesis of individual teeth, there is also a neotenic retention of jaw-wide dental patterning in reptiles. Finer analysis of regional asymmetries revealed changes to which contralateral position shed first, affecting up to one quarter of the jaw (10 tooth positions). Once established, these patterns were retained longitudinally. Taken together, the data support regional and global mechanisms of coordinating tooth cycling post-hatching.}, } @article {pmid29318727, year = {2018}, author = {Kaur, B and Valach, M and Peña-Diaz, P and Moreira, S and Keeling, PJ and Burger, G and Lukeš, J and Faktorová, D}, title = {Transformation of Diplonema papillatum, the type species of the highly diverse and abundant marine microeukaryotes Diplonemida (Euglenozoa).}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1030-1040}, doi = {10.1111/1462-2920.14041}, pmid = {29318727}, issn = {1462-2920}, abstract = {Diplonema papillatum is the type species of diplonemids, which are among the most abundant and diverse heterotrophic microeukaryotes in the world's oceans. Diplonemids are also known for a unique form of post-transcriptional processing in mitochondria. However, the lack of reverse genetics methodologies in these protists has hampered elucidation of their cellular and molecular biology. Here we report a protocol for D. papillatum transformation. We have identified several antibiotics to which D. papillatum is sensitive and thus are suitable selectable markers, and focus in particular on puromycin. Constructs were designed encoding antibiotic resistance markers, fluorescent tags, and additional genomic sequences from D. papillatum to facilitate vector integration into chromosomes. We established conditions for effective electroporation, and demonstrate that electroporated constructs can be stably integrated in the D. papillatum nuclear genome. In D. papillatum transformants, the heterologous puromycin resistance gene is transcribed into mRNA and translated into protein, as determined by Southern hybridization, reverse transcription, and Western blot analyses. This is the first documented case of transformation in a euglenozoan protist outside the well-studied kinetoplastids, making D. papillatum a genetically tractable organism and potentially a model system for marine microeukaryotes.}, } @article {pmid29318721, year = {2018}, author = {van der Stel, AX and van de Lest, CHA and Huynh, S and Parker, CT and van Putten, JPM and Wösten, MMSM}, title = {Catabolite repression in Campylobacter jejuni correlates with intracellular succinate levels.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1374-1388}, doi = {10.1111/1462-2920.14042}, pmid = {29318721}, issn = {1462-2920}, abstract = {Bacteria have evolved different mechanisms to catabolize carbon sources from nutrient mixtures. They first consume their preferred carbon source, before others are used. Regulatory mechanisms adapt the metabolism accordingly to maximize growth and to outcompete other organisms. The human pathogen Campylobacter jejuni is an asaccharolytic Gram-negative bacterium that catabolizes amino acids and organic acids for growth. It prefers serine and aspartate as carbon sources, however it lacks all regulators known to be involved in regulating carbon source utilization in other organisms. In which manner C. jejuni adapts its metabolism towards the presence or absence of preferred carbon sources is unknown. In this study, we show with transcriptomic analysis and enzyme assays how C. jejuni adapts its metabolism in response to its preferred carbon sources. In the presence of serine as well as lactate and pyruvate C. jejuni inhibits the utilization of other carbon sources, by repressing the expression of a number of central metabolic enzymes. The regulatory proteins RacR, Cj1000 and CsrA play a role in the regulation of these metabolic enzymes. This metabolism dependent transcriptional repression correlates with an accumulation of intracellular succinate. Hence, we propose a demand-based catabolite repression mechanism in C. jejuni, depended on intracellular succinate levels.}, } @article {pmid29318340, year = {2018}, author = {Muiños-Bühl, A and González-Recio, O and Muñoz, M and Óvilo, C and García-Casco, J and Fernández, AI}, title = {Evaluating Protocols for Porcine Faecal Microbiome Recollection, Storage and DNA Extraction: from the Farm to the Lab.}, journal = {Current microbiology}, volume = {75}, number = {6}, pages = {651-657}, pmid = {29318340}, issn = {1432-0991}, support = {AGL2014-56369-C2//Ministerio de Economía y Competitividad/ ; Treasure//Horizon 2020 Framework Programme/ ; }, mesh = {Animals ; DNA, Bacterial/genetics ; Feces/*microbiology ; Gastrointestinal Microbiome/genetics ; Microbiota/*genetics ; RNA, Ribosomal, 16S/genetics ; Swine ; }, abstract = {There is a growing interest in understanding the role of the gut microbiome on productive and meat quality-related traits in livestock species in order to develop new useful tools for improving pig production systems and industry. Faecal samples are analysed as a proxy of gut microbiota and here the selection of suitable protocols for faecal sampling and DNA isolation is a critical first step in order to obtain reliable results, even more to compare results obtained from different studies. The aim of the current study was to establish in a cost-effective way, using automated ribosomal intergenic spacer analysis technique, a protocol for porcine faecal sampling and storage at farm and slaughterhouse and to determine the most efficient microbiota DNA isolation kit among those most widely used. Operational Taxonomic Unit profiles were compared from Iberian pig faecal samples collected from rectum or ground, stored with liquid N2, room temperature or RNAlater, and processed with QIAamp DNA Stool (Qiagen), PowerFecal DNA Isolation (Mobio) or SpeedTools Tissue DNA extraction (Biotools) commercial kits. The results, focused on prokaryote sampling, based on DNA yield and quality, OTU number and Sørensen similarity Indexes, indicate that the recommended protocol for porcine faecal microbiome sampling at farm should include: the collection from porcine rectum to avoid contamination; the storage in liquid N2 or even at room temperature, but not in RNAlater; and the isolation of microbiota DNA using PowerFecal DNA Isolation kit. These conditions provide more reliable DNA samples for further microbiome analysis.}, } @article {pmid29317543, year = {2018}, author = {Watson, T}, title = {Inner Workings: Fishing for artifacts beneath the waves.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {231-233}, pmid = {29317543}, issn = {1091-6490}, mesh = {Animals ; Archaeology/*methods ; Artifacts ; DNA, Ancient/analysis ; Fossils ; *Geological Phenomena ; Humans ; Oceans and Seas ; Seawater ; *Water Movements ; }, } @article {pmid29317540, year = {2018}, author = {De Dreu, CKW}, title = {Giving decision-makers nondiagnostic person information promotes trust within and across nations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E844-E845}, pmid = {29317540}, issn = {1091-6490}, mesh = {*Decision Making ; Personally Identifiable Information ; *Trust ; }, } @article {pmid29317539, year = {2018}, author = {Romano, A and Balliet, D and Yamagishi, T and Liu, JH}, title = {Reply to De Dreu: Shared partner nationality promotes ingroup favoritism in cooperation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E846-E847}, pmid = {29317539}, issn = {1091-6490}, mesh = {*Ethnic Groups ; Group Processes ; Humans ; *Interpersonal Relations ; Social Identification ; }, } @article {pmid29317538, year = {2018}, author = {Robbins, NE and Dinneny, JR}, title = {Growth is required for perception of water availability to pattern root branches in plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E822-E831}, pmid = {29317538}, issn = {1091-6490}, support = {T32 GM007276/GM/NIGMS NIH HHS/United States ; }, mesh = {Gene Expression Regulation, Plant ; *Models, Biological ; Plant Development ; Plant Roots/*growth & development ; Water/*physiology ; Zea mays ; }, abstract = {Water availability is a potent regulator of plant development and induces root branching through a process termed hydropatterning. Hydropatterning enables roots to position lateral branches toward regions of high water availability, such as wet soil or agar media, while preventing their emergence where water is less available, such as in air. The mechanism by which roots perceive the spatial distribution of water during hydropatterning is unknown. Using primary roots of Zea mays (maize) we reveal that developmental competence for hydropatterning is limited to the growth zone of the root tip. Past work has shown that growth generates gradients in water potential across an organ when asymmetries exist in the distribution of available water. Using mathematical modeling, we predict that substantial growth-sustained water potential gradients are also generated in the hydropatterning competent zone and that such biophysical cues inform the patterning of lateral roots. Using diverse chemical and environmental treatments we experimentally demonstrate that growth is necessary for normal hydropatterning of lateral roots. Transcriptomic characterization of the local response of tissues to a moist surface or air revealed extensive regulation of signaling and physiological pathways, some of which we show are growth-dependent. Our work supports a "sense-by-growth" mechanism governing hydropatterning, by which water availability cues are rendered interpretable through growth-sustained water movement.}, } @article {pmid29317537, year = {2018}, author = {Linz, DM and Tomoyasu, Y}, title = {Dual evolutionary origin of insect wings supported by an investigation of the abdominal wing serial homologs in Tribolium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E658-E667}, pmid = {29317537}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; Genes, Homeobox ; *Genes, Insect ; Tribolium/*genetics ; *Wings, Animal ; }, abstract = {The origin of insect wings is still a highly debated mystery in biology, despite the importance of this evolutionary innovation. There are currently two prominent, but contrasting wing origin hypotheses (the tergal origin hypothesis and the pleural origin hypothesis). Through studies in the Tribolium beetle, we have previously obtained functional evidence supporting a third hypothesis, the dual origin hypothesis. Although this hypothesis can potentially unify the two competing hypotheses, it requires further testing from various fields. Here, we investigated the genetic regulation of the tissues serially homologous to wings in the abdomen, outside of the appendage-bearing segments, in Tribolium We found that the formation of ectopic wings in the abdomen upon homeotic transformation relies not only on the previously identified abdominal wing serial homolog (gin-trap), but also on a secondary tissue in the pleural location. Using an enhancer trap line of nubbin (a wing lineage marker), we were able to visualize both of these two tissues (of tergal and pleural nature) contributing to form a complete wing. These results support the idea that the presence of two distinct sets of wing serial homologs per segment represents an ancestral state of the wing serial homologs, and can therefore further support a dual evolutionary origin of insect wings. Our analyses also uncovered detailed Hox regulation of abdominal wing serial homologs, which can be used as a foundation to elucidate the molecular mechanisms that have facilitated the evolution of bona fide insect wings, as well as the diversification of other wing serial homologs.}, } @article {pmid29317536, year = {2018}, author = {Sbodio, JI and Snyder, SH and Paul, BD}, title = {Golgi stress response reprograms cysteine metabolism to confer cytoprotection in Huntington's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {780-785}, pmid = {29317536}, issn = {1091-6490}, support = {R01 MH018501/MH/NIMH NIH HHS/United States ; R37 MH018501/MH/NIMH NIH HHS/United States ; }, mesh = {Activating Transcription Factor 4/*metabolism ; Animals ; Cell Line ; Cystathionine gamma-Lyase/*metabolism ; Cysteine/metabolism ; Golgi Apparatus/*metabolism ; Huntington Disease/*metabolism ; Mice ; Monensin ; Stress, Physiological ; }, abstract = {Golgi stress response is emerging as a physiologic process of comparable importance to endoplasmic reticulum (ER) and mitochondrial stress responses. However, unlike ER stress, the identity of the signal transduction pathway involved in the Golgi stress response has been elusive. We show that the Golgi stressor monensin acts via the PKR-like ER kinase/Activating Transcription Factor 4 pathway. ATF4 is the master regulator of amino acid metabolism, which is induced during amino acid depletion and other forms of stress. One of the genes regulated by ATF4 is the biosynthetic enzyme for cysteine, cystathionine γ-lyase (CSE), which also plays central roles in maintenance of redox homeostasis. Huntington's disease (HD), a neurodegenerative disorder, is associated with disrupted cysteine metabolism caused by depletion of CSE leading to abnormal redox balance and stress response. Thus, restoring CSE function and cysteine disposition may be beneficial in HD. Accordingly, we harnessed the monensin-ATF4-signaling cascade to stimulate CSE expression by preconditioning cells with monensin, which restores cysteine metabolism and an optimal stress response in HD. These findings have implications for treatment of HD and other diseases associated with redox imbalance and dysregulated ATF4 signaling.}, } @article {pmid29317535, year = {2018}, author = {Rengachari, S and Groiss, S and Devos, JM and Caron, E and Grandvaux, N and Panne, D}, title = {Structural basis of STAT2 recognition by IRF9 reveals molecular insights into ISGF3 function.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E601-E609}, pmid = {29317535}, issn = {1091-6490}, mesh = {Animals ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Interferon-Stimulated Gene Factor 3, gamma Subunit/genetics/*metabolism ; Janus Kinases/metabolism ; Mice ; Point Mutation ; Protein Domains ; STAT2 Transcription Factor/genetics/*metabolism ; Signal Transduction ; }, abstract = {Cytokine signaling through the JAK/STAT pathway controls multiple cellular responses including growth, survival, differentiation, and pathogen resistance. An expansion in the gene regulatory repertoire controlled by JAK/STAT signaling occurs through the interaction of STATs with IRF transcription factors to form ISGF3, a complex that contains STAT1, STAT2, and IRF9 and regulates expression of IFN-stimulated genes. ISGF3 function depends on selective interaction between IRF9, through its IRF-association domain (IAD), with the coiled-coil domain (CCD) of STAT2. Here, we report the crystal structures of the IRF9-IAD alone and in a complex with STAT2-CCD. Despite similarity in the overall structure among respective paralogs, the surface features of the IRF9-IAD and STAT2-CCD have diverged to enable specific interaction between these family members. We derive a model for the ISGF3 complex bound to an ISRE DNA element and demonstrate that the observed interface between STAT2 and IRF9 is required for ISGF3 function in cells.}, } @article {pmid29317534, year = {2018}, author = {Kjærbølling, I and Vesth, TC and Frisvad, JC and Nybo, JL and Theobald, S and Kuo, A and Bowyer, P and Matsuda, Y and Mondo, S and Lyhne, EK and Kogle, ME and Clum, A and Lipzen, A and Salamov, A and Ngan, CY and Daum, C and Chiniquy, J and Barry, K and LaButti, K and Haridas, S and Simmons, BA and Magnuson, JK and Mortensen, UH and Larsen, TO and Grigoriev, IV and Baker, SE and Andersen, MR}, title = {Linking secondary metabolites to gene clusters through genome sequencing of six diverse Aspergillus species.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E753-E761}, pmid = {29317534}, issn = {1091-6490}, mesh = {Aflatoxins/biosynthesis/*genetics ; Allergens/genetics ; Aspergillus/*genetics/*metabolism/pathogenicity ; DNA Methylation ; Evolution, Molecular ; Flavonoids/biosynthesis ; Genome, Fungal ; Indole Alkaloids/metabolism ; *Multigene Family ; Phylogeny ; Secondary Metabolism/*genetics ; Terpenes/metabolism ; Whole Genome Sequencing ; }, abstract = {The fungal genus of Aspergillus is highly interesting, containing everything from industrial cell factories, model organisms, and human pathogens. In particular, this group has a prolific production of bioactive secondary metabolites (SMs). In this work, four diverse Aspergillus species (A. campestris, A. novofumigatus, A. ochraceoroseus, and A. steynii) have been whole-genome PacBio sequenced to provide genetic references in three Aspergillus sections. A. taichungensis and A. candidus also were sequenced for SM elucidation. Thirteen Aspergillus genomes were analyzed with comparative genomics to determine phylogeny and genetic diversity, showing that each presented genome contains 15-27% genes not found in other sequenced Aspergilli. In particular, A. novofumigatus was compared with the pathogenic species A. fumigatus This suggests that A. novofumigatus can produce most of the same allergens, virulence, and pathogenicity factors as A. fumigatus, suggesting that A. novofumigatus could be as pathogenic as A. fumigatus Furthermore, SMs were linked to gene clusters based on biological and chemical knowledge and analysis, genome sequences, and predictive algorithms. We thus identify putative SM clusters for aflatoxin, chlorflavonin, and ochrindol in A. ochraceoroseus, A. campestris, and A. steynii, respectively, and novofumigatonin, ent-cycloechinulin, and epi-aszonalenins in A. novofumigatus Our study delivers six fungal genomes, showing the large diversity found in the Aspergillus genus; highlights the potential for discovery of beneficial or harmful SMs; and supports reports of A. novofumigatus pathogenicity. It also shows how biological, biochemical, and genomic information can be combined to identify genes involved in the biosynthesis of specific SMs.}, } @article {pmid29317533, year = {2018}, author = {Domingue, BW and Belsky, DW and Fletcher, JM and Conley, D and Boardman, JD and Harris, KM}, title = {The social genome of friends and schoolmates in the National Longitudinal Study of Adolescent to Adult Health.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {702-707}, pmid = {29317533}, issn = {1091-6490}, support = {P01 HD031921/HD/NICHD NIH HHS/United States ; R01 HD060726/HD/NICHD NIH HHS/United States ; R01 HD073342/HD/NICHD NIH HHS/United States ; P30 AG034424/AG/NIA NIH HHS/United States ; P2C HD047879/HD/NICHD NIH HHS/United States ; P2C HD047873/HD/NICHD NIH HHS/United States ; P30 AG028716/AG/NIA NIH HHS/United States ; P2C HD066613/HD/NICHD NIH HHS/United States ; R01 AG032282/AG/NIA NIH HHS/United States ; }, mesh = {Adolescent ; Adolescent Behavior/psychology ; Adult ; Female ; Friends/psychology ; Genome-Wide Association Study/methods ; Genotype ; Humans ; Interpersonal Relations ; Longitudinal Studies ; Male ; *Peer Group ; Schools ; *Social Behavior ; Social Environment ; Social Support ; Sociobiology/*methods ; United States ; Young Adult ; }, abstract = {Humans tend to form social relationships with others who resemble them. Whether this sorting of like with like arises from historical patterns of migration, meso-level social structures in modern society, or individual-level selection of similar peers remains unsettled. Recent research has evaluated the possibility that unobserved genotypes may play an important role in the creation of homophilous relationships. We extend this work by using data from 5,500 adolescents from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to examine genetic similarities among pairs of friends. Although there is some evidence that friends have correlated genotypes, both at the whole-genome level as well as at trait-associated loci (via polygenic scores), further analysis suggests that meso-level forces, such as school assignment, are a principal source of genetic similarity between friends. We also observe apparent social-genetic effects in which polygenic scores of an individual's friends and schoolmates predict the individual's own educational attainment. In contrast, an individual's height is unassociated with the height genetics of peers.}, } @article {pmid29317532, year = {2018}, author = {Fadeev, A and Mendoza-Garcia, P and Irion, U and Guan, J and Pfeifer, K and Wiessner, S and Serluca, F and Singh, AP and Nüsslein-Volhard, C and Palmer, RH}, title = {ALKALs are in vivo ligands for ALK family receptor tyrosine kinases in the neural crest and derived cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E630-E638}, pmid = {29317532}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Anaplastic Lymphoma Kinase ; Animals ; Cell Line, Tumor ; Cytokines/*metabolism ; Drosophila ; Eye/metabolism ; Humans ; Lymphoma/enzymology ; Neural Crest/enzymology ; PC12 Cells ; Pigmentation ; Protein-Tyrosine Kinases/*metabolism ; Rats ; Receptor Protein-Tyrosine Kinases/*metabolism ; Zebrafish ; Zebrafish Proteins/*metabolism ; }, abstract = {Mutations in anaplastic lymphoma kinase (ALK) are implicated in somatic and familial neuroblastoma, a pediatric tumor of neural crest-derived tissues. Recently, biochemical analyses have identified secreted small ALKAL proteins (FAM150, AUG) as potential ligands for human ALK and the related leukocyte tyrosine kinase (LTK). In the zebrafish Danio rerio, DrLtk, which is similar to human ALK in sequence and domain structure, controls the development of iridophores, neural crest-derived pigment cells. Hence, the zebrafish system allows studying Alk/Ltk and Alkals involvement in neural crest regulation in vivo. Using zebrafish pigment pattern formation, Drosophila eye patterning, and cell culture-based assays, we show that zebrafish Alkals potently activate zebrafish Ltk and human ALK driving downstream signaling events. Overexpression of the three DrAlkals cause ectopic iridophore development, whereas loss-of-function alleles lead to spatially distinct patterns of iridophore loss in zebrafish larvae and adults. alkal loss-of-function triple mutants completely lack iridophores and are larval lethal as is the case for ltk null mutants. Our results provide in vivo evidence of (i) activation of ALK/LTK family receptors by ALKALs and (ii) an involvement of these ligand-receptor complexes in neural crest development.}, } @article {pmid29316977, year = {2018}, author = {Pragman, AA and Lyu, T and Baller, JA and Gould, TJ and Kelly, RF and Reilly, CS and Isaacson, RE and Wendt, CH}, title = {The lung tissue microbiota of mild and moderate chronic obstructive pulmonary disease.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {7}, pmid = {29316977}, issn = {2049-2618}, support = {1IK2CX001095//U.S. Department of Veterans Affairs/International ; NA//Minnesota Veterans Medical Research and Education Foundation/International ; UL1 TR002494/TR/NCATS NIH HHS/United States ; UL1 TR000114/TR/NCATS NIH HHS/United States ; 348261//American Lung Association/International ; IK2 CX001095/CX/CSRD VA/United States ; T32 AI055433/AI/NIAID NIH HHS/United States ; 5T32AI055433//National Institute of Allergy and Infectious Diseases/International ; 8UL1TR000114/TR/NCATS NIH HHS/United States ; }, mesh = {Aged ; Aged, 80 and over ; Animals ; Bacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Female ; Humans ; Lung/*microbiology ; Male ; Microbiota ; Middle Aged ; Moths/microbiology ; Nose/microbiology ; Pulmonary Disease, Chronic Obstructive/*microbiology/*surgery ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Oral taxa are often found in the chronic obstructive pulmonary disease (COPD) lung microbiota, but it is not clear if this is due to a physiologic process such as aspiration or experimental contamination at the time of specimen collection.

METHODS: Microbiota samples were obtained from nine subjects with mild or moderate COPD by swabbing lung tissue and upper airway sites during lung lobectomy. Lung specimens were not contaminated with upper airway taxa since they were obtained surgically. The microbiota were analyzed with 16S rRNA gene qPCR and 16S rRNA gene hypervariable region 3 (V3) sequencing. Data analyses were performed using QIIME, SourceTracker, and R.

RESULTS: Streptococcus was the most common genus in the oral, bronchial, and lung tissue samples, and multiple other taxa were present in both the upper and lower airways. Each subject's own bronchial and lung tissue microbiota were more similar to each other than were the bronchial and lung tissue microbiota of two different subjects (permutation test, p = 0.0139), indicating more within-subject similarity than between-subject similarity at these two lung sites. Principal coordinate analysis of all subject samples revealed clustering by anatomic sampling site (PERMANOVA, p = 0.001), but not by subject. SourceTracker analysis found that the sources of the lung tissue microbiota were 21.1% (mean) oral microbiota, 8.7% nasal microbiota, and 70.1% unknown. An analysis using the neutral theory of community ecology revealed that the lung tissue microbiota closely reflects the bronchial, oral, and nasal microbiota (immigration parameter estimates 0.69, 0.62, and 0.74, respectively), with some evidence of ecologic drift occurring in the lung tissue.

CONCLUSION: This is the first study to evaluate the mild-moderate COPD lung tissue microbiota without potential for upper airway contamination of the lung samples. In our small study of subjects with COPD, we found oral and nasal bacteria in the lung tissue microbiota, confirming that aspiration is a source of the COPD lung microbiota.}, } @article {pmid29316966, year = {2018}, author = {Volodina, EV and Volodin, IA and Chelysheva, EV and Frey, R}, title = {Hiss and snort call types of wild-living giraffes Giraffa camelopardalis: acoustic structure and context.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {12}, pmid = {29316966}, issn = {1756-0500}, support = {14-14-00237//Russian Science Foundation/ ; }, mesh = {Acoustics ; Animals ; Female ; Giraffes/*physiology ; Kenya ; Male ; Namibia ; Sound Spectrography ; Vocalization, Animal/*physiology ; }, abstract = {OBJECTIVES: Vocalization as part of vigilance behaviour is widespread across animal taxa, including ruminants. Calls of wild-living giraffes have never been recorded and spectrographically investigated. This study reports the acoustic structure of vigilance-related hiss and snort calls of wild-living giraffes Giraffa camelopardalis.

RESULTS: The hiss and snort calls were emitted during five recording sessions produced by nine individual giraffes (8 adults and 1 subadult) in their natural environment in Namibia (3 individuals) and Kenya (6 individuals). These calls attended vigilance behaviour toward humans in hides or in vehicles and cheetahs as natural predators of giraffe young. This study provides spectrographic analyses of 22 hiss and 20 snort calls. The giraffe hisses were broadband vocalizations of an average duration of 0.72 s (from 0.24 to 1.04 s) and a peak frequency of 0.69 kHz. The giraffe snorts were broadband pulsed calls of an average duration of 0.28 s (from 0.13 to 0.55 s), a peak frequency at 0.20 kHz and comprised a prominent low-frequency pulsation of 23.7 pulses/s. The acoustic structure of giraffe hisses is reminiscent of vigilance-related hisses of musk deer Moschus moschiferus. Giraffe snorts differ from snorts of other ruminants by their prominent pulsed pattern.}, } @article {pmid29316964, year = {2018}, author = {Mastrangelo, S and Biscarini, F and Auzino, B and Ragatzu, M and Spaterna, A and Ciampolini, R}, title = {Genome-wide diversity and runs of homozygosity in the "Braque Français, type Pyrénées" dog breed.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {13}, pmid = {29316964}, issn = {1756-0500}, mesh = {Animals ; Dogs/*genetics ; Female ; France ; Genetic Markers/*genetics ; Genetic Variation/*genetics ; Genome/*genetics ; *Heterozygote ; *Homozygote ; *Inbreeding ; Male ; Polymorphism, Single Nucleotide/*genetics ; }, abstract = {OBJECTIVE: Braque Français, type Pyrénées is a French hunting-dog breed whose origin is traced back to old pointing gun-dogs used to assist hunters in finding and retrieving game. This breed is popular in France, but seldom seen elsewhere. Despite the ancient background, the literature on its genetic characterization is surprisingly scarce. A recent study looked into the demography and inbreeding using pedigree records, but there is yet no report on the use of molecular markers in this breed. The aim of this work was to genotype a population of Braque Français, type Pyrénées dogs with the high-density SNP array to study the genomic diversity of the breed.

RESULTS: The average observed ([Formula: see text]) and expected ([Formula: see text]) heterozygosity were 0.371 ([Formula: see text]) and 0.359 ([Formula: see text]). Effective population size ([Formula: see text]) was 27.5635 runs of homozygosity (ROH) were identified with average length of 2.16 MB. A ROH shared by [Formula: see text] of the dogs was detected at the beginning of chromosome 22. Inbreeding coefficients from marker genotypes were in the range [Formula: see text]. Inbreeding estimated from ROH ([Formula: see text]) had mean [Formula: see text]), with range [0.0526, 0.225]. These results show that the Braque Français, type Pyrénées breed is a relatively inbred population, but with still sufficient genetic variability for conservation and genetic improvement.}, } @article {pmid29316882, year = {2018}, author = {Yang, H and Wang, X and Wei, Y and Deng, Z and Liu, H and Chen, J and Dai, L and Xia, Z and He, G and Li, D}, title = {Transcriptomic analyses reveal molecular mechanisms underlying growth heterosis and weakness of rubber tree seedlings.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {10}, pmid = {29316882}, issn = {1471-2229}, support = {31270651,31570684//National Natural Science Foundation of China/International ; 31200514//National Natural Science Foundation of China/International ; 1630022015003//Fundamental Research Funds for Rubber Research Institute, CATAS/International ; 1630022014006//Fundamental Research Funds for Rubber Research Institute, CATAS/International ; }, mesh = {Gene Expression Profiling ; *Gene Expression Regulation, Plant ; *Genes, Plant ; Hevea/*genetics/growth & development ; *Hybrid Vigor ; Hybridization, Genetic ; Plant Breeding ; Seedlings/genetics/growth & development ; *Transcriptome ; }, abstract = {BACKGROUND: Breeding rubber tree seedling with growth heterosis is vital for natural rubber production. It is the prerequisites for effectively utilizing growth heterosis to elucidate its molecular mechanisms, but the molecular mechanisms remain poorly understood in rubber tree. To elucidate seedling growth heterosis, we conducted comparative transcriptomic analyses between the two hybrids and their parents.

RESULTS: By identifying and comparing differently expressed genes (DEGs), we found that the hybrids (BT 3410 and WC 11) show significantly differential expression profiles from their parents (PR 107 and RRIM 600). In BT 3410-parent triad, 1092 (49.95%) and 1094 (50.05%) DEGs indicated clear underdominance or overdominance, respectively. Whereas in WC 11-parent triad, most DEGs (78.2%, 721) showed low- or high-parent dominance; 160 (17.35%) exhibited expression patterns that are not statistically distinguishable from additivity, and 8 (0.87%) and 33 (3.58%) DEGs exhibited underdominance and overdominance, respectively. Furthermore, some biological processes are differentially regulated between two hybrids. Interestingly, the pathway in response to stimulus is significantly downregulated and metabolic pathways are more highly regulated in BT 3410.

CONCLUSIONS: Taken together, the genotypes, transcriptomes and biological pathways (especially, carbohydrate metabolism) are highly divergent between two hybrids, which may be associated with growth heterosis and weakness. Analyzing gene action models in hybrid-parent triads, we propose that overdominance may play important roles on growth heterosis, whereas dominance on hybrid weakness in rubber tree seedlings. These findings bring new insights into our understanding of growth heterosis of rubber tree seedling.}, } @article {pmid29316879, year = {2018}, author = {Peripolli, E and Stafuzza, NB and Munari, DP and Lima, ALF and Irgang, R and Machado, MA and Panetto, JCDC and Ventura, RV and Baldi, F and da Silva, MVGB}, title = {Assessment of runs of homozygosity islands and estimates of genomic inbreeding in Gyr (Bos indicus) dairy cattle.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {34}, pmid = {29316879}, issn = {1471-2164}, support = {SEG 02.09.07.008.00.00//Empresa Brasileira de Pesquisa Agropecuária/International ; }, mesh = {Animals ; Cattle/*genetics ; Female ; Genomics/*methods ; *Homozygote ; *Inbreeding ; Lactation/*genetics ; Milk ; Phenotype ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Runs of homozygosity (ROH) are continuous homozygous segments of the DNA sequence. They have been applied to quantify individual autozygosity and used as a potential inbreeding measure in livestock species. The aim of the present study was (i) to investigate genome-wide autozygosity to identify and characterize ROH patterns in Gyr dairy cattle genome; (ii) identify ROH islands for gene content and enrichment in segments shared by more than 50% of the samples, and (iii) compare estimates of molecular inbreeding calculated from ROH (FROH), genomic relationship matrix approach (FGRM) and based on the observed versus expected number of homozygous genotypes (FHOM), and from pedigree-based coefficient (FPED).

RESULTS: ROH were identified in all animals, with an average number of 55.12 ± 10.37 segments and a mean length of 3.17 Mb. Short segments (ROH1-2 Mb) were abundant through the genomes, which accounted for 60% of all segments identified, even though the proportion of the genome covered by them was relatively small. The findings obtained in this study suggest that on average 7.01% (175.28 Mb) of the genome of this population is autozygous. Overlapping ROH were evident across the genomes and 14 regions were identified with ROH frequencies exceeding 50% of the whole population. Genes associated with lactation (TRAPPC9), milk yield and composition (IRS2 and ANG), and heat adaptation (HSF1, HSPB1, and HSPE1), were identified. Inbreeding coefficients were estimated through the application of FROH, FGRM, FHOM, and FPED approaches. FPED estimates ranged from 0.00 to 0.327 and FROH from 0.001 to 0.201. Low to moderate correlations were observed between FPED-FROH and FGRM-FROH, with values ranging from -0.11 to 0.51. Low to high correlations were observed between FROH-FHOM and moderate between FPED-FHOM and FGRM-FHOM. Correlations between FROH from different lengths and FPED gradually increased with ROH length.

CONCLUSIONS: Genes inside ROH islands suggest a strong selection for dairy traits and enrichment for Gyr cattle environmental adaptation. Furthermore, low FPED-FROH correlations for small segments indicate that FPED estimates are not the most suitable method to capture ancient inbreeding. The existence of a moderate correlation between larger ROH indicates that FROH can be used as an alternative to inbreeding estimates in the absence of pedigree records.}, } @article {pmid29316496, year = {2018}, author = {Sousa, FL and Preiner, M and Martin, WF}, title = {Native metals, electron bifurcation, and CO2 reduction in early biochemical evolution.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {77-83}, doi = {10.1016/j.mib.2017.12.010}, pmid = {29316496}, issn = {1879-0364}, mesh = {Anaerobiosis ; Autotrophic Processes/physiology ; Bacteria/genetics/growth & development ; *Bacterial Physiological Phenomena ; Carbon Dioxide/*metabolism ; *Electrons ; Energy Metabolism ; Hydrogen/metabolism ; Metals/chemistry/*metabolism ; Oxidation-Reduction ; }, abstract = {Molecular hydrogen is an ancient source of energy and electrons. Anaerobic autotrophs that harness the H2/CO2 redox couple harbour ancient biochemical traits that trace back to the universal common ancestor. Aspects of their physiology, including the abundance of transition metals, radical reaction mechanisms, and their main exergonic bioenergetic reactions, forge links between ancient microbes and geochemical reactions at hydrothermal vents. The midpoint potential of H2 however requires anaerobes that reduce CO2 with H2 to use flavin based electron bifurcation-a mechanism to conserve energy as low potential reduced ferredoxins via soluble proteins-for CO2 fixation. This presents a paradox. At the onset of biochemical evolution, before there were proteins, how was CO2 reduced using H2? FeS minerals alone are probably not the solution, because biological CO2 reduction is a two electron reaction. Physiology can provide clues. Some acetogens and some methanogens can grow using native iron (Fe0) instead of H2 as the electron donor. In the laboratory, Fe0 efficiently reduces CO2 to acetate and methanol. Hydrothermal vents harbour awaruite, Ni3Fe, a natural compound of native metals. Native metals might have been the precursors of electron bifurcation in biochemical evolution.}, } @article {pmid29316210, year = {2018}, author = {Shbailat, SJ and Aslan, IO}, title = {Fate of egg proteins during the development of Columba livia domestica embryo.}, journal = {Journal of experimental zoology. Part B, Molecular and developmental evolution}, volume = {330}, number = {1}, pages = {23-32}, doi = {10.1002/jez.b.22786}, pmid = {29316210}, issn = {1552-5015}, mesh = {Animals ; Columbidae/*embryology ; Egg Proteins/*metabolism ; Electrophoresis ; Embryo, Nonmammalian/*physiology ; Embryonic Development ; Peptide Hydrolases/metabolism ; }, abstract = {The transfer of egg white into the yolk and consumption of yolk proteins by the embryo are largely unexplored in the pigeon Columba livia domestica. Here, we investigated the route of egg white transfer as well as the degradation and uptake of yolk proteins by the pigeon embryo. Initially, we tested the electrophoretic patterns of proteins in different egg compartments throughout development. Then, we used lysozyme as a reference protein to follow the egg white transfer, and we measured its activity using Micrococcus lysodeikticus as a substrate. Moreover, we determined the general protease activity during different developmental stages in the yolk using casein. Finally, we examined the expression of aminopeptidase-N (APN) and oligopeptide transporter PepT1 genes in the yolk sac membrane (YSM) from incubation day 8 until day 17. Several electrophoretic bands of presumptive egg white proteins appeared in different egg compartments. Also, lysozyme activity was detected chronologically in the egg compartments. It appeared on day 12 in the amniotic and intestinal fluids and on day 14 in the yolk. Moreover, protease activity in the yolk increased significantly on day 14 and thereafter. APN expression was largest on day 8 and reduced generally afterward, whereas PepT1 expression peaked between days 13 and 15 but then reduced substantially. Our results suggest that the egg white proteins move through the amnion and intestine into the yolk where they undergo degradation by the activated proteases. Furthermore, the YSM appears to have a role in protein consumption, and this role decreases toward hatch.}, } @article {pmid29315531, year = {2018}, author = {Smithwick, FM and Stubbs, TL}, title = {Phanerozoic survivors: Actinopterygian evolution through the Permo-Triassic and Triassic-Jurassic mass extinction events.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {348-362}, pmid = {29315531}, issn = {1558-5646}, abstract = {Actinopterygians (ray-finned fishes) successfully passed through four of the big five mass extinction events of the Phanerozoic, but the effects of these crises on the group are poorly understood. Many researchers have assumed that the Permo-Triassic mass extinction (PTME) and end-Triassic extinction (ETE) had little impact on actinopterygians, despite devastating many other groups. Here, two morphometric techniques, geometric (body shape) and functional (jaw morphology), are used to assess the effects of these two extinction events on the group. The PTME elicits no significant shifts in functional disparity while body shape disparity increases. An expansion of body shape and functional disparity coincides with the neopterygian radiation and evolution of novel feeding adaptations in the Middle-Late Triassic. Through the ETE, small decreases are seen in shape and functional disparity, but are unlikely to represent major changes brought about by the extinction event. In the Early Jurassic, further expansions into novel areas of ecospace indicative of durophagy occur, potentially linked to losses in the ETE. As no evidence is found for major perturbations in actinopterygian evolution through either extinction event, the group appears to have been immune to two major environmental crises that were disastrous to most other organisms.}, } @article {pmid29315523, year = {2018}, author = {Vincent, AM}, title = {Digest: Going solo: Self-fertilization in haploid algae may not lead to evolutionary decline.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {409-410}, doi = {10.1111/evo.13420}, pmid = {29315523}, issn = {1558-5646}, } @article {pmid29315521, year = {2018}, author = {Jayaswal, V and Jimenez, J and Magie, R and Nguyen, K and Clifton, B and Yeh, S and Ranz, JM}, title = {A species-specific multigene family mediates differential sperm displacement in Drosophila melanogaster.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {399-403}, doi = {10.1111/evo.13417}, pmid = {29315521}, issn = {1558-5646}, abstract = {Sperm competition is a postcopulatory sexual selection mechanism in species in which females mate with multiple males. Despite its evolutionary relevance in shaping male traits, the genetic mechanisms underlying sperm competition are poorly understood. A recently originated multigene family specific to Drosophila melanogaster, Sdic, is important for the outcome of sperm competition in doubly mated females, although the mechanistic nature of this phenotype remained unresolved. Here, we compared doubly mated females, second mated to either Sdic knockout or nonknockout males, and directly visualize sperm dynamics in the female reproductive tract. We found that a less effective removal of first-to-mate male's sperm within the female's sperm storage organs is consistent with a reduced sperm competitive ability of the Sdic knockout males. Our results highlight the role young genes can play in driving the evolution of sperm competition.}, } @article {pmid29315519, year = {2018}, author = {Kazemi, B and Gamberale-Stille, G and Wåtz, T and Wiklund, C and Leimar, O}, title = {Learning of salient prey traits explains Batesian mimicry evolution.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {531-539}, doi = {10.1111/evo.13418}, pmid = {29315519}, issn = {1558-5646}, abstract = {Batesian mimicry evolution involves an initial major mutation that produces a rough resemblance to the model, followed by smaller improving changes. To examine the learning psychology of this process, we applied established ideas about mimicry in Papilio polyxenes asterius of the model Battus philenor. We performed experiments with wild birds as predators and butterfly wings as semiartificial prey. Wings of hybrids of P. p. asterius and Papilio machaon were used to approximate the first mutant, with melanism as the hypothesized first mimetic trait. Based on previous results about learning psychology and imperfect mimicry, we predicted that: melanism should have high salience (i.e., being noticeable and prominent), meaning that predators readily discriminate a melanistic mutant from appearances similar to P. machaon; the difference between the first mutant and the model should have intermediate salience to allow further improvement of mimicry; and the final difference in appearance between P. p. asterius and B. philenor should have very low salience, causing improvement to level off. Our results supported both the traditional hypothesis and all our predictions about relative salience. We conclude that there is good agreement between long-held ideas about how Batesian mimicry evolves and recent insights from learning psychology about the role of salience in mimicry evolution.}, } @article {pmid29314644, year = {2018}, author = {Fowler, SJ and Palomo, A and Dechesne, A and Mines, PD and Smets, BF}, title = {Comammox Nitrospira are abundant ammonia oxidizers in diverse groundwater-fed rapid sand filter communities.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1002-1015}, doi = {10.1111/1462-2920.14033}, pmid = {29314644}, issn = {1462-2920}, abstract = {The recent discovery of completely nitrifying Nitrospira demands a re-examination of nitrifying environments to evaluate their contribution to nitrogen cycling. To approach this challenge, tools are needed to detect and quantify comammox Nitrospira. We present primers for the simultaneous quantification and diversity assessement of both comammox Nitrospira clades. The primers cover a wide range of comammox diversity, spanning all available high quality sequences. We applied these primers to 12 groundwater-fed rapid sand filters, and found comammox Nitrospira to be abundant in all filters. Clade B comammox comprise the majority (∼75%) of comammox abundance in all filters. Nitrosomonadaceae were present in all filters, although at low abundance (mean = 1.8%). Ordination suggests that temperature impacts the structure of nitrifying communities, and in particular that increasing temperature favours Nitrospira. The nitrogen content of the filter material, sulfate concentration and surface ammonium loading rates shape the structure of the comammox guild in the filters. This work provides an assay for simultaneous detection and diversity assessment of clades A and B comammox Nitrospira, expands our current knowledge of comammox Nitrospira diversity and demonstrates a key role for comammox Nitrospira in nitrification in groundwater-fed biofilters.}, } @article {pmid29314604, year = {2018}, author = {Pratscher, J and Vollmers, J and Wiegand, S and Dumont, MG and Kaster, AK}, title = {Unravelling the Identity, Metabolic Potential and Global Biogeography of the Atmospheric Methane-Oxidizing Upland Soil Cluster α.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {1016-1029}, doi = {10.1111/1462-2920.14036}, pmid = {29314604}, issn = {1462-2920}, abstract = {Understanding of global methane sources and sinks is a prerequisite for the design of strategies to counteract global warming. Microbial methane oxidation in soils represents the largest biological sink for atmospheric methane. However, still very little is known about the identity, metabolic properties and distribution of the microbial group proposed to be responsible for most of this uptake, the uncultivated upland soil cluster α (USCα). Here, we reconstructed a draft genome of USCα from a combination of targeted cell sorting and metagenomes from forest soil, providing the first insights into its metabolic potential and environmental adaptation strategies. The 16S rRNA gene sequence recovered was distinctive and suggests this crucial group as a new genus within the Beijerinckiaceae, close to Methylocapsa. Application of a fluorescently labelled suicide substrate for the particulate methane monooxygenase enzyme (pMMO) coupled to 16S rRNA fluorescence in situ hybridisation (FISH) allowed for the first time a direct link of the high-affinity activity of methane oxidation to USCα cells in situ. Analysis of the global biogeography of this group further revealed its presence in previously unrecognized habitats, such as subterranean and volcanic biofilm environments, indicating a potential role of these environments in the biological sink for atmospheric methane.}, } @article {pmid29314504, year = {2018}, author = {Yang, Z and Zhou, X and Ma, Y and Zhou, M and Waldor, MK and Zhang, Y and Wang, Q}, title = {Serine/threonine kinase PpkA coordinates the interplay between T6SS2 activation and quorum sensing in the marine pathogen Vibrio alginolyticus.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {903-919}, doi = {10.1111/1462-2920.14039}, pmid = {29314504}, issn = {1462-2920}, abstract = {Type VI secretion systems (T6SS) are multiprotein secretion machines that can mediate killing of bacterial cells and thereby modify the composition of bacterial communities. The mechanisms that control the production of and secretion of these killing machines are incompletely understood, although quorum sensing (QS) and the PpkA kinase modulate T6SS activity in some organisms. Here we investigated control the T6S in the marine organism Vibrio alginolyticus EPGS, which encodes two T6SS systems (T6SS1 and T6SS2). We found that the organism principally relies on T6SS2 for interbacterial competition. We further carried out a phosphoproteomic screen to identify substrates of the T6SS2-linked PpkA2 kinase. Substrates of PpkA2 encoded within the T6SS2 cluster as well proteins that are apparently not linked to T6SS-related processes were identified. Similar to other organisms, PpkA2 autophosphorylation was critical for T6SS2 function. Notably, phosphorylation of a polypeptide encoded outside of the T6SS2 cluster, VtsR, was critical for T6SS2 expression and function because it augments the expression of luxR, a key regulator of QS that also promotes T6SS2 gene expression. Thus, PpkA2 controls a phosphorylation cascade that mediates a positive regulatory loop entwining T6SS and QS, thereby coordinating these pathways to enhance the competitive fitness of V. alginolyticus.}, } @article {pmid29313868, year = {2018}, author = {Dotto, G and Berlanda, M and Pasotto, D and Mondin, A and Zambotto, G and Menandro, ML}, title = {Pets as potential carriers of multidrug-resistant Enterococcus faecium of significance to public health.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {168-172}, pmid = {29313868}, issn = {1121-7138}, mesh = {Animals ; Carrier State ; Cat Diseases/*microbiology ; Cats ; *Drug Resistance, Multiple, Bacterial ; Enterococcus faecium/*drug effects/*isolation & purification ; Gram-Positive Bacterial Infections/microbiology/*veterinary ; *Pets ; Public Health ; Urinary Tract Infections/microbiology/veterinary ; Zoonoses/microbiology ; }, abstract = {Enterococci are important opportunistic pathogens for humans and animals and have recently become one of the leading causes of nosocomial infections, raising concerns about their virulence and antimicrobial traits. This study describes a multidrug-resistant Enterococcus faecium isolated from a case of feline urinary tract infection. This strain was characterized for virulence and antimicrobial resistance markers, phylogenetic group and sensitivity to antimicrobial agents used routinely in veterinary and human practice. Other than virulence traits, the isolate harboured a variety of antimicrobial-resistance genes and chromosomal mutations, the combination of which conferred resistance to almost all of the antimicrobial compounds tested. Interestingly, this strain harboured mutations in the quinolone resistance-determining regions never been described in E. faecium and conferring resistance to all the quinolones tested. The combination of these resistance features, together with its virulence traits, makes this strain an example of a potentially dangerous pathogen that could easily spread in veterinary hospitals and perhaps to the environment and to humans, seriously compromising patient outcomes.}, } @article {pmid29313867, year = {2018}, author = {Di Pietro, M and Filardo, S and Porpora, MG and Recine, N and Latino, MA and Sessa, R}, title = {HPV/Chlamydia trachomatis co-infection: metagenomic analysis of cervical microbiota in asymptomatic women.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {34-41}, pmid = {29313867}, issn = {1121-7138}, mesh = {Adult ; Chlamydia Infections/*complications/microbiology ; *Chlamydia trachomatis ; *Coinfection ; Female ; Humans ; *Papillomaviridae ; Papillomavirus Infections/*complications/virology ; RNA, Bacterial/genetics ; RNA, Ribosomal, 16S/genetics ; Uterine Cervical Diseases/*microbiology/pathology ; }, abstract = {HPV and Chlamydia trachomatis are the most common causes of sexually transmitted diseases worldwide. Most infections are asymptomatic and left untreated lead to severe reproductive tract sequelae such as cervical cancer and infertility. Interestingly, C. trachomatis may also increase the susceptibility to HPV infection as well as contribute to viral persistence. Recently, a growing body of evidence has suggested that the composition of the cervico-vaginal microbiota plays a key role in the susceptibility and outcome of genital infections caused by several pathogens, including HPV and C. trachomatis. The aim of our study was to undertake a metagenomic analysis of sequenced 16s rRNA gene amplicons to characterize the cervical microbiota from asymptomatic women with HPV/C. trachomatis co-infection. The composition of the cervical microbiota from HPV-positive or C. trachomatis-positive women was also analysed. The main finding of our study showed that the cervical microbiota in HPV/C. trachomatis co-infected women had a higher microbial diversity than the cervical microbiota in healthy controls (p<0.05). In addition, Aerococcus christensenii was associated with C. trachomatis infection. In conclusion, the increased cervical microbial diversity observed in HPV/C. trachomatis co-infected women and the detection of potential microbiological biomarkers of C. trachomatis infection will open the way to innovative approaches that may be helpful to identify women at risk of co-infection.}, } @article {pmid29313866, year = {2018}, author = {Caio, C and Maugeri, G and Zingali, T and Gona, F and Stefani, S and Mezzatesta, ML}, title = {Extensively drug-resistant ArmA-producing Acinetobacter baumannii in an Italian intensive care unit.}, journal = {The new microbiologica}, volume = {41}, number = {2}, pages = {159-161}, pmid = {29313866}, issn = {1121-7138}, mesh = {Acinetobacter Infections/*microbiology ; Acinetobacter baumannii/*drug effects/genetics ; Anti-Bacterial Agents/*pharmacology/therapeutic use ; Bacterial Proteins/genetics/*metabolism ; Carbapenems/pharmacology ; Cross Infection/microbiology ; Drug Resistance, Multiple, Bacterial/*genetics ; Humans ; Intensive Care Units ; Italy/epidemiology ; Microbial Sensitivity Tests ; }, abstract = {We describe the spread of 12 carbapenem-resistant Acinetobacter baumannii isolates in hospitalized patients. All strains showed an extensively drug-resistant phenotype and high-level of aminoglycoside resistance, harboring the ArmA gene and blaoxa-23 downstream of ISAba1 (transposon Tn2008 arrangement) where both were located on the chromosome. These strains carry a class 1 integron containing the gene cassette aacA4-catB8-aadA1. Molecular analysis revealed that all isolates belonged to the same sequence type (ST) 2 clone. The spread of ArmA-producing A. baumannii strains limit the treatment options showing the dramatic situation which requires novel therapies to limit high mortality rates.}, } @article {pmid29313865, year = {2018}, author = {Lasserre, J and Toma, S and Dos Santos-Gonçalvez, AM and Leprince, J and Leloup, G and Brecx, M}, title = {Evaluation of Emdogain® antimicrobial effectiveness against biofilms containing the keystone pathogen Porphyromonas gingivalis.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {73-76}, pmid = {29313865}, issn = {1121-7138}, mesh = {Biofilms/*drug effects/growth & development ; Culture Media ; Dental Enamel Proteins/*pharmacology ; Porphyromonas gingivalis/*drug effects/physiology ; }, abstract = {This study aimed to evaluate the antimicrobial activity of Emdogain® (EMD) against biofilms containing the periopathogen Porphyromonas gingivalis. A brain-Heart infusion broth inoculated with S. gordonii and P. gingivalis was perfused (7-d, anaerobiosis) through a closed circuit containing two Robbins devices as to form biofilms. The latter were then treated for 2 min with various antimicrobials (Chlorhexidine (CHX) 0.2%, Povidone iodine (PVI) 5%, PVI 10%, essential oils (EO), EO ZeroTM or EMD) (n=8) and cell densities were calculated and compared. In the present in vitro model, Emdogain® was not statistically effective (p>0.05) in killing biofilm bacteria unlike the other tested molecules.}, } @article {pmid29313864, year = {2018}, author = {La Fauci, V and Costa, GB and Arena, A and Ventura Spagnolo, E and Genovese, C and Palamara, MA and Squeri, R}, title = {Trend of MDR-microorganisms isolated from the biological samples of patients with HAI and from the surfaces around that patient.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {42-46}, pmid = {29313864}, issn = {1121-7138}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/*drug effects ; Bacterial Infections/*microbiology ; Cross Infection/*microbiology ; *Drug Resistance, Multiple, Bacterial ; Environmental Microbiology ; Female ; Humans ; Italy ; Male ; Retrospective Studies ; }, abstract = {Healthcare-associated infections (HAI) continue to be a major public health concern. A number of epidemiologically relevant HAI microorganisms are multidrug-resistant (MDR) germs that can spread rapidly and/or carry multiple resistance to antibiotics. They are the cause of high mortality and possible nosocomial epidemics. For this reason, we implemented microbiological surveillance acquiring samples from patients with HAI and environmental samples from the surfaces surrounding those patients. A retrospective study was carried out from January 2014 to December 2016 in two departments of the University Hospital in Messina, Italy: the Microbiology and the Hygiene Laboratories. A comparison was made between the microbiological isolates found on the patients and the microorganisms typed further to environmental sampling on the surfaces adjacent to the patient with HAI. There was a 24% match in 2014, 22% in 2015 and 20% in 2016 on total isolates. The most common isolates belonged to the Enterobacteriacae family: in particular, an ever-increasing trend has been registered for Klebsiella spp; Acinetobacter baumannii and multiresistant Pseudomonas aeruginosa have seen a growing trend for both patient and environmental samples. During the three years, the highest infection prevalence rate was found in Anaesthesia and Resuscitation, followed by Thoracic and Vascular Surgery.}, } @article {pmid29313863, year = {2018}, author = {Delfino, E and Fucile, C and Del Bono, V and Marchese, A and Marini, V and Coppo, E and Casciaro, R and Minicucci, L and Giacobbe, DR and Martelli, A and Viscoli, C and Mattioli, F}, title = {Pharmacokinetics of high-dose extended-infusion meropenem during pulmonary exacerbation in adult cystic fibrosis patients: a case series.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {47-51}, pmid = {29313863}, issn = {1121-7138}, mesh = {Adult ; Anti-Bacterial Agents/administration & dosage/pharmacokinetics/therapeutic use ; Cystic Fibrosis/*drug therapy ; Dose-Response Relationship, Drug ; Drug Administration Schedule ; Drug Resistance, Bacterial ; Female ; Humans ; Male ; Meropenem ; Microbial Sensitivity Tests ; Middle Aged ; Pseudomonas Infections/blood/*drug therapy ; Pseudomonas aeruginosa/drug effects ; Thienamycins/administration & dosage/blood/*pharmacokinetics/*therapeutic use ; }, abstract = {This case series explored the pharmacokinetic/pharmacodynamic (PK/PD) characteristics of meropenem (MEM) in adult cystic fibrosis (CF) patients hospitalized for a pulmonary exacerbation. From January 2015 to June 2016, all adult patients with cystic fibrosis (CF) and chronic pulmonary infection due to meropenem (MEM)-susceptible/intermediate Pseudomonas aeruginosa who received at least 48 h of MEM as an extended 3-hour infusion for treating a pulmonary exacerbation were enrolled. MEM plasma concentrations were determined by high-performance liquid chromatography. Six adult CF patients with a median age of 47 years were included in the study. MEM showed a high Vd (mean 45.98 L, standard deviation [SD] ±34.45). A minimal PK/PD target of 40% T > minimum inhibitory concentration (MIC) with respect to the MEM MIC of P. aeruginosa strains isolated from sputum during exacerbation was achieved in 5/6 patients (83%). MEM failed to achieve this target only in one patient, whose strain showed the highest MEM MIC in our cohort (8 mg/L). In all patients, MEM was well tolerated, and no adverse events were reported. In conclusion, high-dose, extended-infusion MEM during pulmonary exacerbation showed a high Vd in six adult CF patients with high median age, and was well tolerated.}, } @article {pmid29311701, year = {2018}, author = {Brown, JH and Hall, CAS and Sibly, RM}, title = {Equal fitness paradigm explained by a trade-off between generation time and energy production rate.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {262-268}, doi = {10.1038/s41559-017-0430-1}, pmid = {29311701}, issn = {2397-334X}, abstract = {Most plant, animal and microbial species of widely varying body size and lifestyle are nearly equally fit as evidenced by their coexistence and persistence through millions of years. All organisms compete for a limited supply of organic chemical energy, derived mostly from photosynthesis, to invest in the two components of fitness: survival and production. All organisms are mortal because molecular and cellular damage accumulates over the lifetime; life persists only because parents produce offspring. We call this the equal fitness paradigm. The equal fitness paradigm occurs because: (1) there is a trade-off between generation time and productive power, which have equal-but-opposite scalings with body size and temperature; smaller and warmer organisms have shorter lifespans but produce biomass at higher rates than larger and colder organisms; (2) the energy content of biomass is essentially constant, ~22.4 kJ g-1 dry body weight; and (3) the fraction of biomass production incorporated into surviving offspring is also roughly constant, ~10-50%. As organisms transmit approximately the same quantity of energy per gram to offspring in the next generation, no species has an inherent lasting advantage in the struggle for existence. The equal fitness paradigm emphasizes the central importance of energy, biological scaling relations and power-time trade-offs in life history, ecology and evolution.}, } @article {pmid29311700, year = {2018}, author = {Pleška, M and Lang, M and Refardt, D and Levin, BR and Guet, CC}, title = {Phage-host population dynamics promotes prophage acquisition in bacteria with innate immunity.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {359-366}, doi = {10.1038/s41559-017-0424-z}, pmid = {29311700}, issn = {2397-334X}, abstract = {Temperate bacteriophages integrate in bacterial genomes as prophages and represent an important source of genetic variation for bacterial evolution, frequently transmitting fitness-augmenting genes such as toxins responsible for virulence of major pathogens. However, only a fraction of bacteriophage infections are lysogenic and lead to prophage acquisition, whereas the majority are lytic and kill the infected bacteria. Unless able to discriminate lytic from lysogenic infections, mechanisms of immunity to bacteriophages are expected to act as a double-edged sword and increase the odds of survival at the cost of depriving bacteria of potentially beneficial prophages. We show that although restriction-modification systems as mechanisms of innate immunity prevent both lytic and lysogenic infections indiscriminately in individual bacteria, they increase the number of prophage-acquiring individuals at the population level. We find that this counterintuitive result is a consequence of phage-host population dynamics, in which restriction-modification systems delay infection onset until bacteria reach densities at which the probability of lysogeny increases. These results underscore the importance of population-level dynamics as a key factor modulating costs and benefits of immunity to temperate bacteriophages.}, } @article {pmid29311699, year = {2018}, author = {Mead, R and Hejmadi, M and Hurst, LD}, title = {Scientific aptitude better explains poor responses to teaching of evolution than psychological conflicts.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {388-394}, doi = {10.1038/s41559-017-0442-x}, pmid = {29311699}, issn = {2397-334X}, abstract = {It is considered a myth that non-acceptance of scientific consensus on emotive topics is owing to difficulties processing scientific information and is, instead, owing to belief-associated psychological conflicts, the strongest non-acceptors being highly educated. It has been unclear whether these results from adults explain variation in response to school-level teaching. We studied a cohort of UK secondary school students (aged 14-16) and assessed their acceptance and understanding of evolution. In addition, to address their aptitude for science we assessed their understanding of genetics and their teacher-derived assessment of science aptitude. As both models predict, students with low initial evolution acceptance scores showed lower increases in the understanding of evolution. Contrary to conventional wisdom, this effect is better explained by lack of aptitude: before teaching, students with low acceptance had lower understanding of both evolution and of genetics; the low-acceptance students sat disproportionately in the foundation (rather than higher) science classes; low-acceptance students showed lower increments in the understanding of genetics; and student gain in the understanding of evolution correlated positively with gain in the understanding of genetics. We find no evidence either for a role for psychological conflict in determining response to teaching or that strong rejectors are more commonly of a higher ability. From qualitative data we hypothesize that religious students can avoid psychological conflict by adopting a compatibilist attitude. We conclude that there are students recalcitrant to the teaching of science (as currently taught) and that these students are more likely to not accept the scientific consensus. Optimizing methods to teach recalcitrant students is an important avenue for research.}, } @article {pmid29311645, year = {2018}, author = {Kuru, E and Lambert, C and Rittichier, J and Till, R and Ducret, A and Derouaux, A and Gray, J and Biboy, J and Vollmer, W and VanNieuwenhze, M and Brun, YV and Sockett, RE}, title = {Author Correction: Fluorescent D-amino-acids reveal bi-cellular cell wall modifications important for Bdellovibrio bacteriovorus predation.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {254}, doi = {10.1038/s41564-017-0087-1}, pmid = {29311645}, issn = {2058-5276}, abstract = {In the original version of this Article, a grant number and acknowledgement were omitted. The Acknowledgements section should have stated that one of the 3D SIM microscopes used for this research was supported by Medical Research Council UK grant (MR/K015753/1) to S. Foster, University of Sheffield, UK, and that the authors thank C. Walther and S. Foster for the access and their kind help with this. This has now been corrected in all versions of the Article.}, } @article {pmid29311644, year = {2018}, author = {Schirmer, M and Franzosa, EA and Lloyd-Price, J and McIver, LJ and Schwager, R and Poon, TW and Ananthakrishnan, AN and Andrews, E and Barron, G and Lake, K and Prasad, M and Sauk, J and Stevens, B and Wilson, RG and Braun, J and Denson, LA and Kugathasan, S and McGovern, DPB and Vlamakis, H and Xavier, RJ and Huttenhower, C}, title = {Dynamics of metatranscription in the inflammatory bowel disease gut microbiome.}, journal = {Nature microbiology}, volume = {3}, number = {3}, pages = {337-346}, pmid = {29311644}, issn = {2058-5276}, support = {U54 DK102557/DK/NIDDK NIH HHS/United States ; U01 DK062413/DK/NIDDK NIH HHS/United States ; P30 DK043351/DK/NIDDK NIH HHS/United States ; R01 DK092405/DK/NIDDK NIH HHS/United States ; P01 DK046763/DK/NIDDK NIH HHS/United States ; UL1 TR001881/TR/NCATS NIH HHS/United States ; }, abstract = {Inflammatory bowel disease (IBD) is a group of chronic diseases of the digestive tract that affects millions of people worldwide. Genetic, environmental and microbial factors have been implicated in the onset and exacerbation of IBD. However, the mechanisms associating gut microbial dysbioses and aberrant immune responses remain largely unknown. The integrative Human Microbiome Project seeks to close these gaps by examining the dynamics of microbiome functionality in disease by profiling the gut microbiomes of >100 individuals sampled over a 1-year period. Here, we present the first results based on 78 paired faecal metagenomes and metatranscriptomes, and 222 additional metagenomes from 59 patients with Crohn's disease, 34 with ulcerative colitis and 24 non-IBD control patients. We demonstrate several cases in which measures of microbial gene expression in the inflamed gut can be informative relative to metagenomic profiles of functional potential. First, although many microbial organisms exhibited concordant DNA and RNA abundances, we also detected species-specific biases in transcriptional activity, revealing predominant transcription of pathways by individual microorganisms per host (for example, by Faecalibacterium prausnitzii). Thus, a loss of these organisms in disease may have more far-reaching consequences than suggested by their genomic abundances. Furthermore, we identified organisms that were metagenomically abundant but inactive or dormant in the gut with little or no expression (for example, Dialister invisus). Last, certain disease-specific microbial characteristics were more pronounced or only detectable at the transcript level, such as pathways that were predominantly expressed by different organisms in patients with IBD (for example, Bacteroides vulgatus and Alistipes putredinis). This provides potential insights into gut microbial pathway transcription that can vary over time, inducing phenotypical changes that are complementary to those linked to metagenomic abundances. The study's results highlight the strength of analysing both the activity and the presence of gut microorganisms to provide insight into the role of the microbiome in IBD.}, } @article {pmid29311637, year = {2018}, author = {Saeed, S and Bonnefond, A and Tamanini, F and Mirza, MU and Manzoor, J and Janjua, QM and Din, SM and Gaitan, J and Milochau, A and Durand, E and Vaillant, E and Haseeb, A and De Graeve, F and Rabearivelo, I and Sand, O and Queniat, G and Boutry, R and Schott, DA and Ayesha, H and Ali, M and Khan, WI and Butt, TA and Rinne, T and Stumpel, C and Abderrahmani, A and Lang, J and Arslan, M and Froguel, P}, title = {Loss-of-function mutations in ADCY3 cause monogenic severe obesity.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {175-179}, doi = {10.1038/s41588-017-0023-6}, pmid = {29311637}, issn = {1546-1718}, abstract = {Study of monogenic forms of obesity has demonstrated the pivotal role of the central leptin-melanocortin pathway in controlling energy balance, appetite and body weight 1 . The majority of loss-of-function mutations (mostly recessive or co-dominant) have been identified in genes that are directly involved in leptin-melanocortin signaling. These genes, however, only explain obesity in <5% of cases, predominantly from outbred populations 2 . We previously showed that, in a consanguineous population in Pakistan, recessive mutations in known obesity-related genes explain ~30% of cases with severe obesity3-5. These data suggested that new monogenic forms of obesity could also be identified in this population. Here we identify and functionally characterize homozygous mutations in the ADCY3 gene encoding adenylate cyclase 3 in children with severe obesity from consanguineous Pakistani families, as well as compound heterozygous mutations in a severely obese child of European-American descent. These findings highlight ADCY3 as an important mediator of energy homeostasis and an attractive pharmacological target in the treatment of obesity.}, } @article {pmid29311636, year = {2018}, author = {Grarup, N and Moltke, I and Andersen, MK and Dalby, M and Vitting-Seerup, K and Kern, T and Mahendran, Y and Jørsboe, E and Larsen, CVL and Dahl-Petersen, IK and Gilly, A and Suveges, D and Dedoussis, G and Zeggini, E and Pedersen, O and Andersson, R and Bjerregaard, P and Jørgensen, ME and Albrechtsen, A and Hansen, T}, title = {Loss-of-function variants in ADCY3 increase risk of obesity and type 2 diabetes.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {172-174}, pmid = {29311636}, issn = {1546-1718}, support = {638273//European Research Council/International ; }, abstract = {We have identified a variant in ADCY3 (encoding adenylate cyclase 3) associated with markedly increased risk of obesity and type 2 diabetes in the Greenlandic population. The variant disrupts a splice acceptor site, and carriers have decreased ADCY3 RNA expression. Additionally, we observe an enrichment of rare ADCY3 loss-of-function variants among individuals with type 2 diabetes in trans-ancestry cohorts. These findings provide new information on disease etiology relevant for future treatment strategies.}, } @article {pmid29311635, year = {2018}, author = {Siljee, JE and Wang, Y and Bernard, AA and Ersoy, BA and Zhang, S and Marley, A and Von Zastrow, M and Reiter, JF and Vaisse, C}, title = {Subcellular localization of MC4R with ADCY3 at neuronal primary cilia underlies a common pathway for genetic predisposition to obesity.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {180-185}, pmid = {29311635}, issn = {1546-1718}, support = {R01 GM095941/GM/NIGMS NIH HHS/United States ; P01 DA010154/DA/NIDA NIH HHS/United States ; P30 DK063720/DK/NIDDK NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; R01 DK060540/DK/NIDDK NIH HHS/United States ; R01 DK106404/DK/NIDDK NIH HHS/United States ; R01 DA012864/DA/NIDA NIH HHS/United States ; R01 DA010711/DA/NIDA NIH HHS/United States ; R01 AR054396/AR/NIAMS NIH HHS/United States ; }, abstract = {Most monogenic cases of obesity in humans have been linked to mutations in genes encoding members of the leptin-melanocortin pathway. Specifically, mutations in MC4R, the melanocortin-4 receptor gene, account for 3-5% of all severe obesity cases in humans1-3. Recently, ADCY3 (adenylyl cyclase 3) gene mutations have been implicated in obesity4,5. ADCY3 localizes to the primary cilia of neurons 6 , organelles that function as hubs for select signaling pathways. Mutations that disrupt the functions of primary cilia cause ciliopathies, rare recessive pleiotropic diseases in which obesity is a cardinal manifestation 7 . We demonstrate that MC4R colocalizes with ADCY3 at the primary cilia of a subset of hypothalamic neurons, that obesity-associated MC4R mutations impair ciliary localization and that inhibition of adenylyl cyclase signaling at the primary cilia of these neurons increases body weight. These data suggest that impaired signaling from the primary cilia of MC4R neurons is a common pathway underlying genetic causes of obesity in humans.}, } @article {pmid29311343, year = {2018}, author = {Heck, AM and Wilusz, J}, title = {The Interplay between the RNA Decay and Translation Machinery in Eukaryotes.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a032839}, pmid = {29311343}, issn = {1943-0264}, abstract = {RNA decay plays a major role in regulating gene expression and is tightly networked with other aspects of gene expression to effectively coordinate post-transcriptional regulation. The goal of this work is to provide an overview of the major factors and pathways of general messenger RNA (mRNA) decay in eukaryotic cells, and then discuss the effective interplay of this cytoplasmic process with the protein synthesis machinery. Given the transcript-specific and fluid nature of mRNA stability in response to changing cellular conditions, understanding the fundamental networking between RNA decay and translation will provide a foundation for a complete mechanistic understanding of this important aspect of cell biology.}, } @article {pmid29311342, year = {2018}, author = {Mitteldorf, J and Fahy, GM}, title = {Questioning the inevitability of aging.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E558}, pmid = {29311342}, issn = {1091-6490}, } @article {pmid29311341, year = {2018}, author = {Nelson, P and Masel, J}, title = {Reply to Mitteldorf and Fahy: Aging is still inevitable.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E559}, pmid = {29311341}, issn = {1091-6490}, } @article {pmid29311340, year = {2018}, author = {Edemir, B}, title = {Considering hypertonicity in the interpretation and analysis of cell type-specific gene expression pattern in the collecting duct.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E349-E350}, pmid = {29311340}, issn = {1091-6490}, mesh = {*Gene Expression ; *Kidney Tubules, Collecting ; }, } @article {pmid29311339, year = {2018}, author = {Chen, L and Lee, JW and Chou, CL and Nair, AV and Battistone, MA and Păunescu, TG and Merkulova, M and Breton, S and Verlander, JW and Wall, SM and Brown, D and Burg, MB and Knepper, MA}, title = {Reply to Edemir: Physiological regulation and single-cell RNA sequencing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E351-E352}, pmid = {29311339}, issn = {1091-6490}, mesh = {*Base Sequence ; High-Throughput Nucleotide Sequencing ; RNA ; *Sequence Analysis, RNA ; Single-Cell Analysis ; }, } @article {pmid29311338, year = {2018}, author = {Conforti, P and Besusso, D and Bocchi, VD and Faedo, A and Cesana, E and Rossetti, G and Ranzani, V and Svendsen, CN and Thompson, LM and Toselli, M and Biella, G and Pagani, M and Cattaneo, E}, title = {Faulty neuronal determination and cell polarization are reverted by modulating HD early phenotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E762-E771}, pmid = {29311338}, issn = {1091-6490}, mesh = {Cell Line ; Cell Polarity ; Humans ; Huntington Disease/genetics/*physiopathology ; Induced Pluripotent Stem Cells ; *Neurogenesis ; Telencephalon/cytology ; }, abstract = {Increasing evidence suggests that early neurodevelopmental defects in Huntington's disease (HD) patients could contribute to the later adult neurodegenerative phenotype. Here, by using HD-derived induced pluripotent stem cell lines, we report that early telencephalic induction and late neural identity are affected in cortical and striatal populations. We show that a large CAG expansion causes complete failure of the neuro-ectodermal acquisition, while cells carrying shorter CAGs repeats show gross abnormalities in neural rosette formation as well as disrupted cytoarchitecture in cortical organoids. Gene-expression analysis showed that control organoid overlapped with mature human fetal cortical areas, while HD organoids correlated with the immature ventricular zone/subventricular zone. We also report that defects in neuroectoderm and rosette formation could be rescued by molecular and pharmacological approaches leading to a recovery of striatal identity. These results show that mutant huntingtin precludes normal neuronal fate acquisition and highlights a possible connection between mutant huntingtin and abnormal neural development in HD.}, } @article {pmid29311337, year = {2018}, author = {Rubin, H and Rubin, AL}, title = {Phenotypic selection as the biological mode of epigenetic conversion and reversion in cell transformation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E725-E732}, pmid = {29311337}, issn = {1091-6490}, mesh = {Adaptation, Biological ; Animals ; *Cell Transformation, Neoplastic ; Cellular Microenvironment ; *Epigenesis, Genetic ; Phenotype ; *Selection, Genetic ; }, abstract = {Exposure of certain cell lines to methylcholanthrene, X-rays, or physiological growth constraint leads to preneoplastic transformation in all or most of the treated cells. After attaining confluence, a fraction in those cells progress to full transformation, as evidenced by their ability to form discrete foci distinguishable from the surrounding cells by virtue of their higher density. Transformation induced by suspension in agar, an even stronger growth-selective condition than confluence, is reminiscent of all but the final differentiated stage of a normal developmental process, epithelial-mesenchymal transition. Changes associated with transformation are not restricted to focus-forming cells, as the permissiveness for focus formation provided by confluent cells surrounding transformed foci is greater than that of nonselected cells. The neoplastic process can also be reversed in culture. Transformed cells passaged at low density in high serum revert to normal morphology and growth behavior in vitro and lose the capacity for tumor formation in vivo. We propose that transformation and its reversal are driven by a process of phenotypic selection that involves entire heterogeneous populations of cells responding to microenvironmental changes. Because of the involvement of whole cell populations, we view this process as fundamentally adaptive and epigenetic in nature.}, } @article {pmid29311336, year = {2018}, author = {Basak, O and Krieger, TG and Muraro, MJ and Wiebrands, K and Stange, DE and Frias-Aldeguer, J and Rivron, NC and van de Wetering, M and van Es, JH and van Oudenaarden, A and Simons, BD and Clevers, H}, title = {Troy+ brain stem cells cycle through quiescence and regulate their number by sensing niche occupancy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E610-E619}, pmid = {29311336}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 294325//European Research Council/International ; 098357/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Cell Lineage ; Cell Proliferation ; Lateral Ventricles/*cytology ; Mice ; Neural Stem Cells/*physiology ; Neurogenesis ; Receptors, Tumor Necrosis Factor/metabolism ; Single-Cell Analysis ; *Stem Cell Niche ; Transcriptome ; }, abstract = {The adult mouse subependymal zone provides a niche for mammalian neural stem cells (NSCs). However, the molecular signature, self-renewal potential, and fate behavior of NSCs remain poorly defined. Here we propose a model in which the fate of active NSCs is coupled to the total number of neighboring NSCs in a shared niche. Using knock-in reporter alleles and single-cell RNA sequencing, we show that the Wnt target Tnfrsf19/Troy identifies both active and quiescent NSCs. Quantitative analysis of genetic lineage tracing of individual NSCs under homeostasis or in response to injury reveals rapid expansion of stem-cell number before some return to quiescence. This behavior is best explained by stochastic fate decisions, where stem-cell number within a shared niche fluctuates over time. Fate mapping proliferating cells using a Ki67iresCreER allele confirms that active NSCs reversibly return to quiescence, achieving long-term self-renewal. Our findings suggest a niche-based mechanism for the regulation of NSC fate and number.}, } @article {pmid29311335, year = {2018}, author = {Woelders, T and Leenheers, T and Gordijn, MCM and Hut, RA and Beersma, DGM and Wams, EJ}, title = {Melanopsin- and L-cone-induced pupil constriction is inhibited by S- and M-cones in humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {792-797}, pmid = {29311335}, issn = {1091-6490}, mesh = {Adult ; Female ; Humans ; Male ; Pupil/*physiology ; Retinal Cone Photoreceptor Cells/*physiology ; Visual Perception ; Young Adult ; }, abstract = {The human retina contains five photoreceptor types: rods; short (S)-, mid (M)-, and long (L)-wavelength-sensitive cones; and melanopsin-expressing ganglion cells. Recently, it has been shown that selective increments in M-cone activation are paradoxically perceived as brightness decrements, as opposed to L-cone increments. Here we show that similar effects are also observed in the pupillary light response, whereby M-cone or S-cone increments lead to pupil dilation whereas L-cone or melanopic illuminance increments resulted in pupil constriction. Additionally, intermittent photoreceptor activation increased pupil constriction over a 30-min interval. Modulation of L-cone or melanopic illuminance within the 0.25-4-Hz frequency range resulted in more sustained pupillary constriction than light of constant intensity. Opposite results were found for S-cone and M-cone modulations (2 Hz), mirroring the dichotomy observed in the transient responses. The transient and sustained pupillary light responses therefore suggest that S- and M-cones provide inhibitory input to the pupillary control system when selectively activated, whereas L-cones and melanopsin response fulfill an excitatory role. These findings provide insight into functional networks in the human retina and the effect of color-coding in nonvisual responses to light, and imply that nonvisual and visual brightness discrimination may share a common pathway that starts in the retina.}, } @article {pmid29311334, year = {2018}, author = {Bai, Y and Olivier, JH and Bullard, G and Liu, C and Therien, MJ}, title = {Dynamics of charged excitons in electronically and morphologically homogeneous single-walled carbon nanotubes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {674-679}, pmid = {29311334}, issn = {1091-6490}, abstract = {The trion, a three-body charge-exciton bound state, offers unique opportunities to simultaneously manipulate charge, spin, and excitation in one-dimensional single-walled carbon nanotubes (SWNTs) at room temperature. Effective exploitation of trion quasi-particles requires fundamental insight into their creation and decay dynamics. Such knowledge, however, remains elusive for SWNT trion states, due to the electronic and morphological heterogeneity of commonly interrogated SWNT samples, and the fact that transient spectroscopic signals uniquely associated with the trion state have not been identified. Here, we prepare length-sorted SWNTs and precisely control charge-carrier-doping densities to determine trion dynamics using femtosecond pump-probe spectroscopy. Identification of the trion transient absorptive hallmark enables us to demonstrate that trions (i) derive from a precursor excitonic state, (ii) are produced via migration of excitons to stationary hole-polaron sites, and (iii) decay in a first-order manner. Importantly, under appropriate carrier-doping densities, exciton-to-trion conversion in SWNTs can approach 100% at ambient temperature. Our findings open up possibilities for exploiting trions in SWNT optoelectronics, ranging from photovoltaics and photodetectors to spintronics.}, } @article {pmid29311333, year = {2018}, author = {Nordbotten, JM and Levin, SA and Szathmáry, E and Stenseth, NC}, title = {Ecological and evolutionary dynamics of interconnectedness and modularity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {750-755}, pmid = {29311333}, issn = {1091-6490}, support = {294332//European Research Council/International ; }, mesh = {Biodiversity ; *Biological Evolution ; Ecology/*methods ; Ecosystem ; Environment ; Models, Theoretical ; Phenotype ; Population Dynamics/*statistics & numerical data ; Selection, Genetic/physiology ; }, abstract = {In this contribution, we develop a theoretical framework for linking microprocesses (i.e., population dynamics and evolution through natural selection) with macrophenomena (such as interconnectedness and modularity within an ecological system). This is achieved by developing a measure of interconnectedness for population distributions defined on a trait space (generalizing the notion of modularity on graphs), in combination with an evolution equation for the population distribution. With this contribution, we provide a platform for understanding under what environmental, ecological, and evolutionary conditions ecosystems evolve toward being more or less modular. A major contribution of this work is that we are able to decompose the overall driver of changes at the macro level (such as interconnectedness) into three components: (i) ecologically driven change, (ii) evolutionarily driven change, and (iii) environmentally driven change.}, } @article {pmid29311332, year = {2018}, author = {Zhang, K and Pitner, XB and Yang, R and Nix, WD and Plummer, JD and Fan, JA}, title = {Single-crystal metal growth on amorphous insulating substrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {685-689}, pmid = {29311332}, issn = {1091-6490}, abstract = {Metal structures on insulators are essential components in advanced electronic and nanooptical systems. Their electronic and optical properties are closely tied to their crystal quality, due to the strong dependence of carrier transport and band structure on defects and grain boundaries. Here we report a method for creating patterned single-crystal metal microstructures on amorphous insulating substrates, using liquid phase epitaxy. In this process, the patterned metal microstructures are encapsulated in an insulating crucible, together with a small seed of a differing material. The system is heated to temperatures above the metal melting point, followed by cooling and metal crystallization. During the heating process, the metal and seed form a high-melting-point solid solution, which directs liquid epitaxial metal growth. High yield of single-crystal metal with different sizes is confirmed with electron backscatter diffraction images, after removing the insulating crucible. Unexpectedly, the metal microstructures crystallize with the [Formula: see text] direction normal to the plane of the film. This platform technology will enable the large-scale integration of high-performance plasmonic and electronic nanosystems.}, } @article {pmid29311331, year = {2018}, author = {Joswiak, MN and Doherty, MF and Peters, B}, title = {Ion dissolution mechanism and kinetics at kink sites on NaCl surfaces.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {656-661}, pmid = {29311331}, issn = {1091-6490}, abstract = {Desolvation barriers are present for solute-solvent exchange events, such as ligand binding to an enzyme active site, during protein folding, and at battery electrodes. For solution-grown crystals, desolvation at kink sites can be the rate-limiting step for growth. However, desolvation and the associated kinetic barriers are poorly understood. In this work, we use rare-event simulation techniques to investigate attachment/detachment events at kink sites of a NaCl crystal in water. We elucidate the desolvation mechanism and present an optimized reaction coordinate, which involves one solute collective variable and one solvent collective variable. The attachment/detachment pathways for Na+ and Cl- are qualitatively similar, with quantitative differences that we attribute to different ion sizes and solvent coordination. The attachment barriers primarily result from kink site desolvation, while detachment barriers largely result from breaking ion-crystal bonds. We compute ion detachment rates from kink sites and compare with results from an independent study. We anticipate that the reaction coordinate and desolvation mechanism identified in this work may be applicable to other alkali halides.}, } @article {pmid29311330, year = {2018}, author = {Kim, S and Yun, SP and Lee, S and Umanah, GE and Bandaru, VVR and Yin, X and Rhee, P and Karuppagounder, SS and Kwon, SH and Lee, H and Mao, X and Kim, D and Pandey, A and Lee, G and Dawson, VL and Dawson, TM and Ko, HS}, title = {GBA1 deficiency negatively affects physiological α-synuclein tetramers and related multimers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {798-803}, pmid = {29311330}, issn = {1091-6490}, support = {U54 HD079123/HD/NICHD NIH HHS/United States ; P50 AG005146/AG/NIA NIH HHS/United States ; P30 DK089502/DK/NIDDK NIH HHS/United States ; R01 NS082205/NS/NINDS NIH HHS/United States ; R21 NS098006/NS/NINDS NIH HHS/United States ; R01 NS093213/NS/NINDS NIH HHS/United States ; R01 AR070751/AR/NIAMS NIH HHS/United States ; P50 NS038377/NS/NINDS NIH HHS/United States ; U24 NS078338/NS/NINDS NIH HHS/United States ; }, mesh = {1-Deoxynojirimycin/analogs & derivatives ; Cell Line, Tumor ; Dopaminergic Neurons/*metabolism ; Glucosylceramidase/*deficiency/genetics ; Glycosphingolipids/*metabolism ; Humans ; Parkinson Disease/*metabolism ; Protein Multimerization ; alpha-Synuclein/*metabolism ; }, abstract = {Accumulating evidence suggests that α-synuclein (α-syn) occurs physiologically as a helically folded tetramer that resists aggregation. However, the mechanisms underlying the regulation of formation of α-syn tetramers are still mostly unknown. Cellular membrane lipids are thought to play an important role in the regulation of α-syn tetramer formation. Since glucocerebrosidase 1 (GBA1) deficiency contributes to the aggregation of α-syn and leads to changes in neuronal glycosphingolipids (GSLs) including gangliosides, we hypothesized that GBA1 deficiency may affect the formation of α-syn tetramers. Here, we show that accumulation of GSLs due to GBA1 deficiency decreases α-syn tetramers and related multimers and increases α-syn monomers in CRISPR-GBA1 knockout (KO) SH-SY5Y cells. Moreover, α-syn tetramers and related multimers are decreased in N370S GBA1 Parkinson's disease (PD) induced pluripotent stem cell (iPSC)-derived human dopaminergic (hDA) neurons and murine neurons carrying the heterozygous L444P GBA1 mutation. Treatment with miglustat to reduce GSL accumulation and overexpression of GBA1 to augment GBA1 activity reverse the destabilization of α-syn tetramers and protect against α-syn preformed fibril-induced toxicity in hDA neurons. Taken together, these studies provide mechanistic insights into how GBA1 regulates the transition from monomeric α-syn to α-syn tetramers and multimers and suggest unique therapeutic opportunities for PD and dementia with Lewy bodies.}, } @article {pmid29311329, year = {2018}, author = {Bélanger, C and Bérubé-Simard, FA and Leduc, E and Bernas, G and Campeau, PM and Lalani, SR and Martin, DM and Bielas, S and Moccia, A and Srivastava, A and Silversides, DW and Pilon, N}, title = {Dysregulation of cotranscriptional alternative splicing underlies CHARGE syndrome.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E620-E629}, pmid = {29311329}, issn = {1091-6490}, support = {R01 DC009410/DC/NIDCD NIH HHS/United States ; R01 DC014456/DC/NIDCD NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; 376482//CIHR/Canada ; }, mesh = {*Alternative Splicing ; Animals ; Antibiotics, Antineoplastic/therapeutic use ; Argonaute Proteins/metabolism ; CHARGE Syndrome/*etiology/metabolism ; COS Cells ; Cercopithecus aethiops ; DNA-Binding Proteins/genetics/metabolism ; *Disease Models, Animal ; Drug Evaluation, Preclinical ; Female ; Humans ; Male ; Mice ; Mice, Transgenic ; Neural Crest/embryology ; Pregnancy ; Proteins/*genetics ; Rabbits ; Rats ; Sirolimus/therapeutic use ; }, abstract = {CHARGE syndrome-which stands for coloboma of the eye, heart defects, atresia of choanae, retardation of growth/development, genital abnormalities, and ear anomalies-is a severe developmental disorder with wide phenotypic variability, caused mainly by mutations in CHD7 (chromodomain helicase DNA-binding protein 7), known to encode a chromatin remodeler. The genetic lesions responsible for CHD7 mutation-negative cases are unknown, at least in part because the pathogenic mechanisms underlying CHARGE syndrome remain poorly defined. Here, we report the characterization of a mouse model for CHD7 mutation-negative cases of CHARGE syndrome generated by insertional mutagenesis of Fam172a (family with sequence similarity 172, member A). We show that Fam172a plays a key role in the regulation of cotranscriptional alternative splicing, notably by interacting with Ago2 (Argonaute-2) and Chd7. Validation studies in a human cohort allow us to propose that dysregulation of cotranscriptional alternative splicing is a unifying pathogenic mechanism for both CHD7 mutation-positive and CHD7 mutation-negative cases. We also present evidence that such splicing defects can be corrected in vitro by acute rapamycin treatment.}, } @article {pmid29311328, year = {2018}, author = {Matsunari, H and Watanabe, M and Nakano, K and Enosawa, S and Umeyama, K and Uchikura, A and Yashima, S and Fukuda, T and Klymiuk, N and Kurome, M and Kessler, B and Wuensch, A and Zakhartchenko, V and Wolf, E and Hanazono, Y and Nagaya, M and Umezawa, A and Nakauchi, H and Nagashima, H}, title = {Modeling lethal X-linked genetic disorders in pigs with ensured fertility.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {708-713}, pmid = {29311328}, issn = {1091-6490}, mesh = {Animals ; Animals, Genetically Modified/genetics ; Breeding ; Chimera ; Cloning, Organism/methods ; Disease Models, Animal ; Embryo Culture Techniques/*methods ; Fertility ; Gene Knockout Techniques/methods ; Genetic Diseases, X-Linked/*genetics ; Genetic Engineering/methods ; Male ; Nuclear Transfer Techniques ; Reproduction/*genetics ; Swine/genetics ; }, abstract = {Genetically engineered pigs play an indispensable role in the study of rare monogenic diseases. Pigs harboring a gene responsible for a specific disease can be efficiently generated via somatic cell cloning. The generation of somatic cell-cloned pigs from male cells with mutation(s) in an X chromosomal gene is a reliable and straightforward method for reproducing X-linked genetic diseases (XLGDs) in pigs. However, the severe symptoms of XLGDs are often accompanied by impaired growth and reproductive disorders, which hinder the reproduction of these valuable model animals. Here, we generated unique chimeric boars composed of mutant cells harboring a lethal XLGD and normal cells. The chimeric boars exhibited the cured phenotype with fertility while carrying and transmitting the genotype of the XLGD. This unique reproduction system permits routine production of XLGD model pigs through the male-based breeding, thereby opening an avenue for translational research using disease model pigs.}, } @article {pmid29311327, year = {2018}, author = {Dubaissi, E and Rousseau, K and Hughes, GW and Ridley, C and Grencis, RK and Roberts, IS and Thornton, DJ}, title = {Functional characterization of the mucus barrier on the Xenopus tropicalis skin surface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {726-731}, pmid = {29311327}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; BB/M021688/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 203128/Z/16/Z//Wellcome Trust/United Kingdom ; }, mesh = {Aeromonas/pathogenicity ; Animals ; Membrane Proteins/metabolism ; Mucins/*metabolism/physiology ; Mucous Membrane/*metabolism/physiology ; Mucus/metabolism/physiology ; Skin/metabolism ; Xenopus/immunology/*metabolism/physiology ; Xenopus Proteins/metabolism ; }, abstract = {Mucosal surfaces represent critical routes for entry and exit of pathogens. As such, animals have evolved strategies to combat infection at these sites, in particular the production of mucus to prevent attachment and to promote subsequent movement of the mucus/microbe away from the underlying epithelial surface. Using biochemical, biophysical, and infection studies, we have investigated the host protective properties of the skin mucus barrier of the Xenopus tropicalis tadpole. Specifically, we have characterized the major structural component of the barrier and shown that it is a mucin glycoprotein (Otogelin-like or Otogl) with similar sequence, domain organization, and structural properties to human gel-forming mucins. This mucin forms the structural basis of a surface barrier (∼6 μm thick), which is depleted through knockdown of Otogl. Crucially, Otogl knockdown leads to susceptibility to infection by the opportunistic pathogen Aeromonas hydrophila To more accurately reflect its structure, tissue localization, and function, we have renamed Otogl as Xenopus Skin Mucin, or MucXS. Our findings characterize an accessible and tractable model system to define mucus barrier function and host-microbe interactions.}, } @article {pmid29311326, year = {2018}, author = {Louie, RHY and Kaczorowski, KJ and Barton, JP and Chakraborty, AK and McKay, MR}, title = {Fitness landscape of the human immunodeficiency virus envelope protein that is targeted by antibodies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E564-E573}, pmid = {29311326}, issn = {1091-6490}, mesh = {Antibodies, Neutralizing/metabolism ; Binding Sites, Antibody/genetics ; CD4 Antigens/genetics/metabolism ; Computer Simulation ; *Genetic Fitness ; HIV Envelope Protein gp160/*genetics/immunology ; Immune Evasion/*genetics ; *Models, Genetic ; *Mutation ; }, abstract = {HIV is a highly mutable virus, and over 30 years after its discovery, a vaccine or cure is still not available. The isolation of broadly neutralizing antibodies (bnAbs) from HIV-infected patients has led to renewed hope for a prophylactic vaccine capable of combating the scourge of HIV. A major challenge is the design of immunogens and vaccination protocols that can elicit bnAbs that target regions of the virus's spike proteins where the likelihood of mutational escape is low due to the high fitness cost of mutations. Related challenges include the choice of combinations of bnAbs for therapy. An accurate representation of viral fitness as a function of its protein sequences (a fitness landscape), with explicit accounting of the effects of coupling between mutations, could help address these challenges. We describe a computational approach that has allowed us to infer a fitness landscape for gp160, the HIV polyprotein that comprises the viral spike that is targeted by antibodies. We validate the inferred landscape through comparisons with experimental fitness measurements, and various other metrics. We show that an effective antibody that prevents immune escape must selectively bind to high escape cost residues that are surrounded by those where mutations incur a low fitness cost, motivating future applications of our landscape for immunogen design.}, } @article {pmid29311325, year = {2018}, author = {Jiang, J and Huang, ZG and Seager, TP and Lin, W and Grebogi, C and Hastings, A and Lai, YC}, title = {Predicting tipping points in mutualistic networks through dimension reduction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E639-E647}, pmid = {29311325}, issn = {1091-6490}, abstract = {Complex networked systems ranging from ecosystems and the climate to economic, social, and infrastructure systems can exhibit a tipping point (a "point of no return") at which a total collapse of the system occurs. To understand the dynamical mechanism of a tipping point and to predict its occurrence as a system parameter varies are of uttermost importance, tasks that are hindered by the often extremely high dimensionality of the underlying system. Using complex mutualistic networks in ecology as a prototype class of systems, we carry out a dimension reduction process to arrive at an effective 2D system with the two dynamical variables corresponding to the average pollinator and plant abundances. We show, using 59 empirical mutualistic networks extracted from real data, that our 2D model can accurately predict the occurrence of a tipping point, even in the presence of stochastic disturbances. We also find that, because of the lack of sufficient randomness in the structure of the real networks, weighted averaging is necessary in the dimension reduction process. Our reduced model can serve as a paradigm for understanding and predicting the tipping point dynamics in real world mutualistic networks for safeguarding pollinators, and the general principle can be extended to a broad range of disciplines to address the issues of resilience and sustainability.}, } @article {pmid29311324, year = {2018}, author = {Gehman, AM and Hall, RJ and Byers, JE}, title = {Host and parasite thermal ecology jointly determine the effect of climate warming on epidemic dynamics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {744-749}, pmid = {29311324}, issn = {1091-6490}, mesh = {Acclimatization/physiology ; Animals ; Climate Change ; Ecology ; Epidemics ; Host-Parasite Interactions/genetics/*physiology ; Hot Temperature/*adverse effects ; Life Cycle Stages/physiology ; Models, Biological ; Parasites/*physiology ; Temperature ; }, abstract = {Host-parasite systems have intricately coupled life cycles, but each interactor can respond differently to changes in environmental variables like temperature. Although vital to predicting how parasitism will respond to climate change, thermal responses of both host and parasite in key traits affecting infection dynamics have rarely been quantified. Through temperature-controlled experiments on an ectothermic host-parasite system, we demonstrate an offset in the thermal optima for survival of infected and uninfected hosts and parasite production. We combine experimentally derived thermal performance curves with field data on seasonal host abundance and parasite prevalence to parameterize an epidemiological model and forecast the dynamical responses to plausible future climate-warming scenarios. In warming scenarios within the coastal southeastern United States, the model predicts sharp declines in parasite prevalence, with local parasite extinction occurring with as little as 2 °C warming. The northern portion of the parasite's current range could experience local increases in transmission, but assuming no thermal adaptation of the parasite, we find no evidence that the parasite will expand its range northward under warming. This work exemplifies that some host populations may experience reduced parasitism in a warming world and highlights the need to measure host and parasite thermal performance to predict infection responses to climate change.}, } @article {pmid29311323, year = {2018}, author = {Mirpour, K and Bolandnazar, Z and Bisley, JW}, title = {Suppression of frontal eye field neuronal responses with maintained fixation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {804-809}, pmid = {29311323}, issn = {1091-6490}, support = {R01 EY019273/EY/NEI NIH HHS/United States ; }, mesh = {Animals ; *Fixation, Ocular ; Frontal Lobe/*physiology ; Macaca mulatta ; *Saccades ; }, abstract = {The decision of where to make an eye movement is thought to be driven primarily by responses to stimuli in neurons' receptive fields (RFs) in oculomotor areas, including the frontal eye field (FEF) of prefrontal cortex. It is also thought that a saccade may be generated when the accumulation of this activity in favor of one location or another reaches a threshold. However, in the reading and scene perception fields, it is well known that the properties of the stimulus at the fovea often affect when the eyes leave that stimulus. We propose that if FEF plays a role in generating eye movements, then the identity of the stimulus at fixation should affect the FEF responses so as to reduce the probability of making a saccade when fixating an item of interest. Using a visual foraging task in which animals could make multiple eye movements within a single trial, we found that responses were strongly modulated by the identity of the stimulus at the fovea. Specifically, responses to the stimulus in the RF were suppressed when the animal maintained fixation for longer durations on a stimulus that could be associated with a reward. We suggest that this suppression, which was predicted by models of eye movement behavior, could be a mechanism by which FEF can modulate the temporal flow of saccades based on the importance of the stimulus at the fovea.}, } @article {pmid29311322, year = {2018}, author = {Li, R and Goswami, U and King, M and Chen, J and Cesario, TC and Rentzepis, PM}, title = {In situ detection of live-to-dead bacteria ratio after inactivation by means of synchronous fluorescence and PCA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {668-673}, pmid = {29311322}, issn = {1091-6490}, mesh = {Bacteria/metabolism ; Cell Count/*methods ; Fluorescence ; Microbial Viability/drug effects ; Principal Component Analysis/methods ; Spectrometry, Fluorescence/*methods/statistics & numerical data ; Ultraviolet Therapy/methods ; }, abstract = {The determination of live and dead bacteria is of considerable significance for preventing health care-associated infection in hospitals, field clinics, and other areas. In this study, the viable (live) and nonviable (dead) bacteria in a sample were determined by means of their fluorescence spectra and principal component analysis (PCA). Data obtained in this study show that it is possible to identify bacteria strains and determine the live/dead ratio after UV light inactivation and antibiotic treatment, in situ, within minutes. In addition, synchronous fluorescence scans enable the identification of bacterial components such as tryptophan, tyrosine, and DNA. Compared with the time-consuming plating and culturing methods, this study renders a means for rapid detection and determination of live and dead bacteria.}, } @article {pmid29311321, year = {2018}, author = {Zarulli, V and Barthold Jones, JA and Oksuzyan, A and Lindahl-Jacobsen, R and Christensen, K and Vaupel, JW}, title = {Women live longer than men even during severe famines and epidemics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E832-E840}, pmid = {29311321}, issn = {1091-6490}, support = {P01 AG031719/AG/NIA NIH HHS/United States ; P30 AG034424/AG/NIA NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Child ; Child, Preschool ; *Enslavement ; Female ; Humans ; Iceland/epidemiology ; Infant ; *Life Expectancy ; Longevity ; Male ; Measles/mortality ; Middle Aged ; *Sex Characteristics ; Starvation/*mortality ; Young Adult ; }, abstract = {Women in almost all modern populations live longer than men. Research to date provides evidence for both biological and social factors influencing this gender gap. Conditions when both men and women experience extremely high levels of mortality risk are unexplored sources of information. We investigate the survival of both sexes in seven populations under extreme conditions from famines, epidemics, and slavery. Women survived better than men: In all populations, they had lower mortality across almost all ages, and, with the exception of one slave population, they lived longer on average than men. Gender differences in infant mortality contributed the most to the gender gap in life expectancy, indicating that newborn girls were able to survive extreme mortality hazards better than newborn boys. Our results confirm the ubiquity of a female survival advantage even when mortality is extraordinarily high. The hypothesis that the survival advantage of women has fundamental biological underpinnings is supported by the fact that under very harsh conditions females survive better than males even at infant ages when behavioral and social differences may be minimal or favor males. Our findings also indicate that the female advantage differs across environments and is modulated by social factors.}, } @article {pmid29311320, year = {2018}, author = {Qin, C and Colwell, LJ}, title = {Power law tails in phylogenetic systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {690-695}, pmid = {29311320}, issn = {1091-6490}, mesh = {Algorithms ; Evolution, Molecular ; Models, Theoretical ; Multivariate Analysis ; Phylogeny ; Proteins/chemistry ; Sequence Alignment/*methods/statistics & numerical data ; Sequence Analysis, Protein/*methods ; }, abstract = {Covariance analysis of protein sequence alignments uses coevolving pairs of sequence positions to predict features of protein structure and function. However, current methods ignore the phylogenetic relationships between sequences, potentially corrupting the identification of covarying positions. Here, we use random matrix theory to demonstrate the existence of a power law tail that distinguishes the spectrum of covariance caused by phylogeny from that caused by structural interactions. The power law is essentially independent of the phylogenetic tree topology, depending on just two parameters-the sequence length and the average branch length. We demonstrate that these power law tails are ubiquitous in the large protein sequence alignments used to predict contacts in 3D structure, as predicted by our theory. This suggests that to decouple phylogenetic effects from the interactions between sequence distal sites that control biological function, it is necessary to remove or down-weight the eigenvectors of the covariance matrix with largest eigenvalues. We confirm that truncating these eigenvectors improves contact prediction.}, } @article {pmid29311319, year = {2018}, author = {Melnikoff, DE and Bailey, AH}, title = {Preferences for moral vs. immoral traits in others are conditional.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E592-E600}, pmid = {29311319}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Aged ; Aged, 80 and over ; Altruism ; Female ; *Goals ; Humans ; Male ; Middle Aged ; *Morals ; Motivation ; Perception ; *Social Desirability ; Trust ; Young Adult ; }, abstract = {The preference for morality in others is regarded as a dominant factor in person perception. Moral traits are thought to foster liking, and immoral traits are thought to foster disliking, irrespective of the context in which they are embedded. We report the results of four studies that oppose this view. Using both explicit and implicit measures, we found that the preference for morality vs. immorality in others is conditional on the evaluator's current goals. Specifically, when immorality was conducive to participants' current goals, the preference for moral vs. immoral traits in others was eliminated or reversed. The preferences for mercifulness vs. mercilessness (experiment 1), honesty vs. dishonesty (experiment 2), sexual fidelity vs. infidelity (experiment 3), and altruism vs. selfishness (experiment 4) were all found to be conditional. These findings oppose the consensus view that people have a dominant preference for moral vs. immoral traits in others. Our findings also speak to nativist and empiricist theories of social preferences and the stability of the "social contract" underlying productive human societies.}, } @article {pmid29311318, year = {2018}, author = {Kaushal, SS and Likens, GE and Pace, ML and Utz, RM and Haq, S and Gorman, J and Grese, M}, title = {Freshwater salinization syndrome on a continental scale.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E574-E583}, pmid = {29311318}, issn = {1091-6490}, mesh = {Hydrogen-Ion Concentration ; Rivers/*chemistry ; *Salinity ; United States ; *Water Pollution ; }, abstract = {Salt pollution and human-accelerated weathering are shifting the chemical composition of major ions in fresh water and increasing salinization and alkalinization across North America. We propose a concept, the freshwater salinization syndrome, which links salinization and alkalinization processes. This syndrome manifests as concurrent trends in specific conductance, pH, alkalinity, and base cations. Although individual trends can vary in strength, changes in salinization and alkalinization have affected 37% and 90%, respectively, of the drainage area of the contiguous United States over the past century. Across 232 United States Geological Survey (USGS) monitoring sites, 66% of stream and river sites showed a statistical increase in pH, which often began decades before acid rain regulations. The syndrome is most prominent in the densely populated eastern and midwestern United States, where salinity and alkalinity have increased most rapidly. The syndrome is caused by salt pollution (e.g., road deicers, irrigation runoff, sewage, potash), accelerated weathering and soil cation exchange, mining and resource extraction, and the presence of easily weathered minerals used in agriculture (lime) and urbanization (concrete). Increasing salts with strong bases and carbonates elevate acid neutralizing capacity and pH, and increasing sodium from salt pollution eventually displaces base cations on soil exchange sites, which further increases pH and alkalinization. Symptoms of the syndrome can include: infrastructure corrosion, contaminant mobilization, and variations in coastal ocean acidification caused by increasingly alkaline river inputs. Unless regulated and managed, the freshwater salinization syndrome can have significant impacts on ecosystem services such as safe drinking water, contaminant retention, and biodiversity.}, } @article {pmid29311317, year = {2018}, author = {Mazor, R and King, EM and Onda, M and Cuburu, N and Addissie, S and Crown, D and Liu, XF and Kishimoto, TK and Pastan, I}, title = {Tolerogenic nanoparticles restore the antitumor activity of recombinant immunotoxins by mitigating immunogenicity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E733-E742}, pmid = {29311317}, issn = {1091-6490}, mesh = {Animals ; Antibodies, Neutralizing ; GPI-Linked Proteins/immunology ; Humans ; *Immunomodulation ; Immunosuppressive Agents/*administration & dosage ; Immunotoxins/*administration & dosage/immunology ; Leukemia/*therapy ; Nanoparticles ; Sirolimus/*administration & dosage ; Time Factors ; }, abstract = {Protein-based drugs are very active in treating cancer, but their efficacy can be limited by the formation of neutralizing antidrug antibodies (ADAs). Recombinant immunotoxins are proteins that are very effective in patients with leukemia, where immunity is suppressed, but induce ADAs, which compromise their activity, in patients with intact immunity. Here we induced a specific, durable, and transferable immune tolerance to recombinant immunotoxins by combining them with nanoparticles containing rapamycin (SVP-R). SVP-R mitigated the formation of inhibitory ADAs in naïve and sensitized mice, resulting in restoration of antitumor activity. The immune tolerance is mediated by colocalization of the SVP-R and immunotoxin to dendritic cells and macrophages in the spleen and is abrogated by depletion of regulatory T cells. Tolerance induced by SVPs was not blocked by checkpoint inhibitors or costimulatory agonist monoclonal antibodies that by themselves enhance ADA formation.}, } @article {pmid29311316, year = {2018}, author = {Choo, YM and Xu, P and Hwang, JK and Zeng, F and Tan, K and Bhagavathy, G and Chauhan, KR and Leal, WS}, title = {Reverse chemical ecology approach for the identification of an oviposition attractant for Culex quinquefasciatus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {714-719}, pmid = {29311316}, issn = {1091-6490}, support = {R01 AI095514/AI/NIAID NIH HHS/United States ; }, mesh = {Acetaldehyde/chemistry/*metabolism ; Animals ; Culex/genetics/*physiology ; Culicidae/metabolism ; Ecology ; Female ; Mosquito Vectors/metabolism ; Odorants ; Oviposition/physiology ; Pheromones/metabolism/physiology ; Receptors, Odorant/genetics/*metabolism ; Smell ; }, abstract = {Pheromones and other semiochemicals play a crucial role in today's integrated pest and vector management strategies. These semiochemicals are typically discovered by bioassay-guided approaches. Here, we applied a reverse chemical ecology approach; that is, we used olfactory proteins to lead us to putative semiochemicals. Specifically, we used 7 of the top 10 odorant receptors (ORs) most expressed in the antennae of the southern house mosquito, Culex quinquefasciatus, and which are yet to be deorphanized. We expressed these receptors in the Xenopus oocyte recording system and challenged them with a panel of 230 odorants, including physiologically and behaviorally active compounds. Six of the ORs were silent either because they are not functional or a key odorant was missing. CquiOR36, which showed the highest transcript levels of all OR genes in female antennae, was also silent to all odorants in the tested panel, but yielded robust responses when it was accidentally challenged with an old sample of nonanal in ethanol. After confirming that fresh samples were inactive and through a careful investigation of all possible "contaminants" in the old nonanal samples, we identified the active ligand as acetaldehyde. That acetaldehyde is activating CquiOR36 was further confirmed by electroantennogram recordings from antennae of fruit flies engineered to carry CquiOR36. Antennae of female mosquitoes also responded to acetaldehyde. Cage oviposition and dual-choice assays demonstrated that acetaldehyde is an oviposition attractant in a wide range of concentrations and thus of potential practical applications.}, } @article {pmid29311315, year = {2018}, author = {}, title = {Correction for Boxell et al., Greater Internet use is not associated with faster growth in political polarization among US demographic groups.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E556}, doi = {10.1073/pnas.1721401115}, pmid = {29311315}, issn = {1091-6490}, } @article {pmid29311314, year = {2018}, author = {Saker, P and Farrell, MJ and Egan, GF and McKinley, MJ and Denton, DA}, title = {Influence of anterior midcingulate cortex on drinking behavior during thirst and following satiation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {786-791}, pmid = {29311314}, issn = {1091-6490}, mesh = {Adult ; Deglutition ; Drinking Behavior/*physiology ; Female ; Gyrus Cinguli/*physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Middle Aged ; Thirst/*physiology ; }, abstract = {In humans, activity in the anterior midcingulate cortex (aMCC) is associated with both subjective thirst and swallowing. This region is therefore likely to play a prominent role in the regulation of drinking in response to dehydration. Using functional MRI, we investigated this possibility during a period of "drinking behavior" represented by a conjunction of preswallow and swallowing events. These events were examined in the context of a thirsty condition and an "oversated" condition, the latter induced by compliant ingestion of excess fluid. Brain regions associated with swallowing showed increased activity for drinking behavior in the thirsty condition relative to the oversated condition. These regions included the cingulate cortex, premotor areas, primary sensorimotor cortices, the parietal operculum, and the supplementary motor area. Psychophysical interaction analyses revealed increased functional connectivity between the same regions and the aMCC during drinking behavior in the thirsty condition. Functional connectivity during drinking behavior was also greater for the thirsty condition relative to the oversated condition between the aMCC and two subcortical regions, the cerebellum and the rostroventral medulla, the latter containing nuclei responsible for the swallowing reflex. Finally, during drinking behavior in the oversated condition, ratings of swallowing effort showed a negative association with functional connectivity between the aMCC and two cortical regions, the sensorimotor cortex and the supramarginal gyrus. The results of this study provide evidence that the aMCC helps facilitate swallowing during a state of thirst and is therefore likely to contribute to the regulation of drinking after dehydration.}, } @article {pmid29311313, year = {2018}, author = {Almitairi, JOM and Venkatraman Girija, U and Furze, CM and Simpson-Gray, X and Badakshi, F and Marshall, JE and Schwaeble, WJ and Mitchell, DA and Moody, PCE and Wallis, R}, title = {Structure of the C1r-C1s interaction of the C1 complex of complement activation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {768-773}, pmid = {29311313}, issn = {1091-6490}, support = {G1000191//Medical Research Council/United Kingdom ; }, mesh = {Animals ; CHO Cells ; Complement C1r/*metabolism ; Complement C1s/*metabolism ; Cricetulus ; Dimerization ; Protein Domains ; }, abstract = {The multiprotein complex C1 initiates the classical pathway of complement activation on binding to antibody-antigen complexes, pathogen surfaces, apoptotic cells, and polyanionic structures. It is formed from the recognition subcomponent C1q and a tetramer of proteases C1r2C1s2 as a Ca2+-dependent complex. Here we have determined the structure of a complex between the CUB1-EGF-CUB2 fragments of C1r and C1s to reveal the C1r-C1s interaction that forms the core of C1. Both fragments are L-shaped and interlock to form a compact antiparallel heterodimer with a Ca2+ from each subcomponent at the interface. Contacts, involving all three domains of each protease, are more extensive than those of C1r or C1s homodimers, explaining why heterocomplexes form preferentially. The available structural and biophysical data support a model of C1r2C1s2 in which two C1r-C1s dimers are linked via the catalytic domains of C1r. They are incompatible with a recent model in which the N-terminal domains of C1r and C1s form a fixed tetramer. On binding to C1q, the proteases become more compact, with the C1r-C1s dimers at the center and the six collagenous stems of C1q arranged around the perimeter. Activation is likely driven by separation of the C1r-C1s dimer pairs when C1q binds to a surface. Considerable flexibility in C1s likely facilitates C1 complex formation, activation of C1s by C1r, and binding and activation of downstream substrates C4 and C4b-bound C2 to initiate the reaction cascade.}, } @article {pmid29311312, year = {2018}, author = {Ueki, N and Wakabayashi, KI}, title = {Detergent-extracted Volvox model exhibits an anterior-posterior gradient in flagellar Ca2+ sensitivity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {E1061-E1068}, pmid = {29311312}, issn = {1091-6490}, mesh = {Adenosine Triphosphate/chemistry ; Axoneme/physiology ; Calcium/*physiology ; Detergents/*chemistry ; Flagella/*physiology ; Microscopy, Phase-Contrast ; Movement ; Photosynthesis ; *Phototaxis ; Video Recording ; Volvox/*physiology ; }, abstract = {Volvox rousseletii is a multicellular spheroidal green alga containing ∼5,000 cells, each equipped with two flagella (cilia). This organism shows striking photobehavior without any known intercellular communication. To help understand how the behavior of flagella is regulated, we developed a method to extract the whole organism with detergent and reactivate its flagellar motility. Upon addition of ATP, demembranated flagella (axonemes) in the spheroids actively beat and the spheroids swam as if they were alive. Under Ca2+-free conditions, the axonemes assumed planar and asymmetrical waveforms and beat toward the posterior pole, as do live spheroids in the absence of light stimulation. In the presence of 10-6 M Ca2+, however, most axonemes beat three-dimensionally toward the anterior pole, similar to flagella in photostimulated live spheroids. This Ca2+-dependent change in flagellar beating direction was more conspicuous near the anterior pole of the spheroid, but was not observed near the posterior pole. This anterior-posterior gradient of flagellar Ca2+ sensitivity may explain the mechanism of V. rousseletii photobehavior.}, } @article {pmid29311311, year = {2018}, author = {Condello, C and Lemmin, T and Stöhr, J and Nick, M and Wu, Y and Maxwell, AM and Watts, JC and Caro, CD and Oehler, A and Keene, CD and Bird, TD and van Duinen, SG and Lannfelt, L and Ingelsson, M and Graff, C and Giles, K and DeGrado, WF and Prusiner, SB}, title = {Structural heterogeneity and intersubject variability of Aβ in familial and sporadic Alzheimer's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E782-E791}, pmid = {29311311}, issn = {1091-6490}, support = {P01 AG002132/AG/NIA NIH HHS/United States ; R37 AG031220/AG/NIA NIH HHS/United States ; P01 AG010770/AG/NIA NIH HHS/United States ; P50 AG005136/AG/NIA NIH HHS/United States ; P50 NS062684/NS/NINDS NIH HHS/United States ; U01 AG006781/AG/NIA NIH HHS/United States ; }, mesh = {Alzheimer Disease/*etiology ; Amyloid beta-Peptides/genetics/*metabolism ; Animals ; Mice, Transgenic ; Point Mutation ; *Protein Conformation ; *Protein Folding ; }, abstract = {Point mutations in the amyloid-β (Aβ) coding region produce a combination of mutant and WT Aβ isoforms that yield unique clinicopathologies in familial Alzheimer's disease (fAD) and cerebral amyloid angiopathy (fCAA) patients. Here, we report a method to investigate the structural variability of amyloid deposits found in fAD, fCAA, and sporadic AD (sAD). Using this approach, we demonstrate that mutant Aβ determines WT Aβ conformation through prion template-directed misfolding. Using principal component analysis of multiple structure-sensitive fluorescent amyloid-binding dyes, we assessed the conformational variability of Aβ deposits in fAD, fCAA, and sAD patients. Comparing many deposits from a given patient with the overall population, we found that intrapatient variability is much lower than interpatient variability for both disease types. In a given brain, we observed one or two structurally distinct forms. When two forms coexist, they segregate between the parenchyma and cerebrovasculature, particularly in fAD patients. Compared with sAD samples, deposits from fAD patients show less intersubject variability, and little overlap exists between fAD and sAD deposits. Finally, we examined whether E22G (Arctic) or E22Q (Dutch) mutants direct the misfolding of WT Aβ, leading to fAD-like plaques in vivo. Intracerebrally injecting mutant Aβ40 fibrils into transgenic mice expressing only WT Aβ induced the deposition of plaques with many biochemical hallmarks of fAD. Thus, mutant Aβ40 prions induce a conformation of WT Aβ similar to that found in fAD deposits. These findings indicate that diverse AD phenotypes likely arise from one or more initial Aβ prion conformations, which kinetically dominate the spread of prions in the brain.}, } @article {pmid29311310, year = {2018}, author = {}, title = {Correction for Alonso-Mora et al., On-demand high-capacity ride-sharing via dynamic trip-vehicle assignment.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E555}, doi = {10.1073/pnas.1721622115}, pmid = {29311310}, issn = {1091-6490}, } @article {pmid29311309, year = {2018}, author = {Choi, IK and Wang, Z and Ke, Q and Hong, M and Qian, Y and Zhao, X and Liu, Y and Kim, HJ and Ritz, J and Cantor, H and Rajewsky, K and Wucherpfennig, KW and Zhang, B}, title = {Signaling by the Epstein-Barr virus LMP1 protein induces potent cytotoxic CD4+ and CD8+ T cell responses.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E686-E695}, pmid = {29311309}, issn = {1091-6490}, mesh = {4-1BB Ligand/metabolism ; Animals ; B-Lymphocytes/metabolism ; CD27 Ligand/metabolism ; CD4-Positive T-Lymphocytes/*physiology ; CD8-Positive T-Lymphocytes/*physiology ; Herpesvirus 4, Human/*immunology ; Lymphoma/*immunology/virology ; Mice, Inbred BALB C ; Mice, Inbred C57BL ; OX40 Ligand/metabolism ; T-Box Domain Proteins/metabolism ; Viral Matrix Proteins/*immunology ; }, abstract = {The B-lymphotropic Epstein-Barr virus (EBV), pandemic in humans, is rapidly controlled on initial infection by T cell surveillance; thereafter, the virus establishes a lifelong latent infection in the host. If surveillance fails, fatal lymphoproliferation and lymphomagenesis ensue. The initial T cell response consists of predominantly CD8+ cytotoxic T cells and a smaller expansion of CD4+ cells. A major approach to treating EBV-associated lymphomas is adoptive transfer of autologous or allogeneic T cells that are stimulated/expanded on EBV-transformed B cells. Strikingly, the clinical response correlates with the frequency of CD4 cells in the infused T cells. Although in vitro studies suggested that EBV-specific CD4 cells develop cytotoxicity, they have not been comprehensively characterized and the molecular mechanism underlying their formation remains unknown. Our recent work, using a transgenic approach in mice, has revealed a central role for the EBV signaling molecule LMP1 in immune surveillance and transformation of EBV-infected B cells. The mouse model offers a unique tool for uncovering basic features of EBV immunity. Here, we show that LMP1 expression in B cells induces potent cytotoxic CD4 and CD8 T cell responses, by enhancing antigen presentation and costimulation by CD70, OX40 ligand, and 4-1BB ligand. Our data further suggest that cytotoxic CD4 cells hold superior therapeutic value for LMP1 (EBV)-driven lymphomas. These findings provide insights into EBV immunity, demonstrating that LMP1 signaling alone is sufficient to induce a prominent cytotoxic CD4 response, and suggest strategies for immunotherapy in EBV-related and other cancers.}, } @article {pmid29311308, year = {2018}, author = {Panchakshari, RA and Zhang, X and Kumar, V and Du, Z and Wei, PC and Kao, J and Dong, J and Alt, FW}, title = {DNA double-strand break response factors influence end-joining features of IgH class switch and general translocation junctions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {762-767}, pmid = {29311308}, issn = {1091-6490}, support = {F30 CA189740/CA/NCI NIH HHS/United States ; R01 AI077595/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Cell Line ; *DNA Breaks, Double-Stranded ; *DNA End-Joining Repair ; High-Throughput Nucleotide Sequencing ; *Immunoglobulin Class Switching ; Mice ; *Translocation, Genetic ; }, abstract = {Ig heavy chain (IgH) class switch recombination (CSR) in B lymphocytes switches IgH constant regions to change antibody functions. CSR is initiated by DNA double-strand breaks (DSBs) within a donor IgH switch (S) region and a downstream acceptor S region. CSR is completed by fusing donor and acceptor S region DSB ends by classical nonhomologous end-joining (C-NHEJ) and, in its absence, by alternative end-joining that is more biased to use longer junctional microhomologies (MHs). Deficiency for DSB response (DSBR) factors, including ataxia telangiectasia-mutated (ATM) and 53BP1, variably impair CSR end-joining, with 53BP1 deficiency having the greatest impact. However, studies of potential impact of DSBR factor deficiencies on MH-mediated CSR end-joining have been technically limited. We now use a robust DSB joining assay to elucidate impacts of deficiencies for DSBR factors on CSR and chromosomal translocation junctions in primary mouse B cells and CH12F3 B-lymphoma cells. Compared with wild-type, CSR and c-myc to S region translocation junctions in the absence of 53BP1, and, to a lesser extent, other DSBR factors, have increased MH utilization; indeed, 53BP1-deficient MH profiles resemble those associated with C-NHEJ deficiency. However, translocation junctions between c-myc DSB and general DSBs genome-wide are not MH-biased in ATM-deficient versus wild-type CH12F3 cells and are less biased in 53BP1- and C-NHEJ-deficient cells than CSR junctions or c-myc to S region translocation junctions. We discuss potential roles of DSBR factors in suppressing increased MH-mediated DSB end-joining and features of S regions that may render their DSBs prone to MH-biased end-joining in the absence of DSBR factors.}, } @article {pmid29311307, year = {2018}, author = {Brahma, A and Mandal, S and Gadagkar, R}, title = {Emergence of cooperation and division of labor in the primitively eusocial wasp Ropalidia marginata.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {756-761}, pmid = {29311307}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal/physiology ; *Cooperative Behavior ; Female ; Reproduction/physiology ; Sexual Behavior, Animal/*physiology ; Social Behavior ; Social Dominance ; Wasps/*physiology ; }, abstract = {In most primitively eusocial wasps new nests are initiated by a single female or by small groups of females. To study the emergence of division of labor (DOL) among the nest foundresses and to determine its possible effect on nest productivity we maintained newly eclosed females of Ropalidia marginata in small boxes with one, two, or three nestmate wasps of the same age per box. Only one wasp developed her ovaries and laid eggs in each box, while the other wasp(s) built the nest, brought food, and fed larvae, demonstrating the spontaneous emergence of reproductive DOL in the presence of more than one wasp. In nests with three wasps there was also a strong negative correlation between intranidal and extranidal work performed by the two nonreproductive workers, suggesting the spontaneous emergence of nonreproductive DOL; such nonreproductive DOL was absent in nests with two wasps. Both reproductive and nonreproductive DOL were modulated by dominance behavior (DB). In nests with two wasps the egg layer showed significantly more DB than the non-egg layer before nest initiation; in nests with three wasps queens showed significantly more DB than intranidal workers, which in turn showed significantly more DB than extranidal workers. Productivities of nests (as measured by total brood on the day of eclosion of the first adult) initiated by one or two wasps were not different from each other but were significantly lower than that of three wasps. Thus, nonreproductive DOL, and not merely reproductive DOL, is necessary for increase in productivity.}, } @article {pmid29311306, year = {2018}, author = {Chernov-Rogan, T and Li, T and Lu, G and Verschoof, H and Khakh, K and Jones, SW and Beresini, MH and Liu, C and Ortwine, DF and McKerrall, SJ and Hackos, DH and Sutherlin, D and Cohen, CJ and Chen, J}, title = {Mechanism-specific assay design facilitates the discovery of Nav1.7-selective inhibitors.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E792-E801}, pmid = {29311306}, issn = {1091-6490}, mesh = {Animals ; Drug Discovery/*methods ; High-Throughput Screening Assays ; Humans ; Insect Proteins ; Membrane Potentials ; *Molecular Targeted Therapy ; NAV1.7 Voltage-Gated Sodium Channel/drug effects/genetics ; Rats ; Veratridine ; Voltage-Gated Sodium Channel Blockers/*analysis ; Wasp Venoms ; }, abstract = {Many ion channels, including Nav1.7, Cav1.3, and Kv1.3, are linked to human pathologies and are important therapeutic targets. To develop efficacious and safe drugs, subtype-selective modulation is essential, but has been extremely difficult to achieve. We postulate that this challenge is caused by the poor assay design, and investigate the Nav1.7 membrane potential assay, one of the most extensively employed screening assays in modern drug discovery. The assay uses veratridine to activate channels, and compounds are identified based on the inhibition of veratridine-evoked activities. We show that this assay is biased toward nonselective pore blockers and fails to detect the most potent, selective voltage-sensing domain 4 (VSD4) blockers, including PF-05089771 (PF-771) and GX-936. By eliminating a key binding site for pore blockers and replacing veratridine with a VSD-4 binding activator, we directed the assay toward non-pore-blocking mechanisms and discovered Nav1.7-selective chemical scaffolds. Hence, we address a major hurdle in Nav1.7 drug discovery, and this mechanistic approach to assay design is applicable to Cav3.1, Kv1.3, and many other ion channels to facilitate drug discovery.}, } @article {pmid29311305, year = {2018}, author = {Poulin, RX and Lavoie, S and Siegel, K and Gaul, DA and Weissburg, MJ and Kubanek, J}, title = {Chemical encoding of risk perception and predator detection among estuarine invertebrates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {662-667}, pmid = {29311305}, issn = {1091-6490}, mesh = {Animals ; Aquatic Organisms/metabolism ; Brachyura/metabolism/physiology ; Cues ; Ecology ; Ecosystem ; Fear/*physiology ; Feeding Behavior/*physiology ; Marine Biology ; Metabolomics/methods ; Predatory Behavior/*physiology ; Risk Reduction Behavior ; Urine/chemistry ; }, abstract = {An effective strategy for prey to survive in habitats rich in predators is to avoid being noticed. Thus, prey are under selection pressure to recognize predators and adjust their behavior, which can impact numerous community-wide interactions. Many animals in murky and turbulent aquatic environments rely on waterborne chemical cues. Previous research showed that the mud crab, Panopeus herbstii, recognizes the predatory blue crab, Callinectus sapidus, via a cue in blue crab urine. This cue is strongest if blue crabs recently preyed upon mud crabs. Subsequently, mud crabs suppress their foraging activity, reducing predation by blue crabs. Using NMR spectroscopy- and mass spectrometry-based metabolomics, chemical variation in urine from blue crabs fed different diets was related to prey behavior. We identified the urinary metabolites trigonelline and homarine as components of the cue that mud crabs use to detect blue crabs, with concentrations of each metabolite dependent on the blue crab's diet. At concentrations found naturally in blue crab urine, trigonelline and homarine, alone as well as in a mixture, alerted mud crabs to the presence of blue crabs, leading to decreased foraging by mud crabs. Risk perception by waterborne cues has been widely observed by ecologists, but the molecular nature of these cues has not been previously identified. Metabolomics provides an opportunity to study waterborne cues where other approaches have historically failed, advancing our understanding of the chemical nature of a wide range of ecological interactions.}, } @article {pmid29311304, year = {2018}, author = {Kleist, NJ and Guralnick, RP and Cruz, A and Lowry, CA and Francis, CD}, title = {Chronic anthropogenic noise disrupts glucocorticoid signaling and has multiple effects on fitness in an avian community.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E648-E657}, pmid = {29311304}, issn = {1091-6490}, mesh = {Animals ; Body Size ; Corticosterone/*blood ; Feathers/growth & development ; Female ; *Genetic Fitness ; *Nesting Behavior ; Noise/*adverse effects ; Songbirds/*blood ; }, abstract = {Anthropogenic noise is a pervasive pollutant that decreases environmental quality by disrupting a suite of behaviors vital to perception and communication. However, even within populations of noise-sensitive species, individuals still select breeding sites located within areas exposed to high noise levels, with largely unknown physiological and fitness consequences. We use a study system in the natural gas fields of northern New Mexico to test the prediction that exposure to noise causes glucocorticoid-signaling dysfunction and decreases fitness in a community of secondary cavity-nesting birds. In accordance with these predictions, and across all species, we find strong support for noise exposure decreasing baseline corticosterone in adults and nestlings and, conversely, increasing acute stressor-induced corticosterone in nestlings. We also document fitness consequences with increased noise in the form of reduced hatching success in the western bluebird (Sialia mexicana), the species most likely to nest in noisiest environments. Nestlings of all three species exhibited accelerated growth of both feathers and body size at intermediate noise amplitudes compared with lower or higher amplitudes. Our results are consistent with recent experimental laboratory studies and show that noise functions as a chronic, inescapable stressor. Anthropogenic noise likely impairs environmental risk perception by species relying on acoustic cues and ultimately leads to impacts on fitness. Our work, when taken together with recent efforts to document noise across the landscape, implies potential widespread, noise-induced chronic stress coupled with reduced fitness for many species reliant on acoustic cues.}, } @article {pmid29311303, year = {2018}, author = {Soto, M and Orliaguet, L and Reyzer, ML and Manier, ML and Caprioli, RM and Kahn, CR}, title = {Pyruvate induces torpor in obese mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {810-815}, pmid = {29311303}, issn = {1091-6490}, support = {P30 DK036836/DK/NIDDK NIH HHS/United States ; P41 GM103391/GM/NIGMS NIH HHS/United States ; R01 DK082659/DK/NIDDK NIH HHS/United States ; R37 DK031036/DK/NIDDK NIH HHS/United States ; }, mesh = {Adenosine/metabolism ; Adipose Tissue, Brown/*metabolism ; Animals ; Brain/metabolism ; Insulin Resistance ; Male ; Mice, Inbred C57BL ; Mice, Obese ; Obesity/*physiopathology ; *Pyruvic Acid ; Torpor/*physiology ; Uncoupling Protein 1/*metabolism ; }, abstract = {Mice subjected to cold or caloric deprivation can reduce body temperature and metabolic rate and enter a state of torpor. Here we show that administration of pyruvate, an energy-rich metabolic intermediate, can induce torpor in mice with diet-induced or genetic obesity. This is associated with marked hypothermia, decreased activity, and decreased metabolic rate. The drop in body temperature correlates with the degree of obesity and is blunted by housing mice at thermoneutrality. Induction of torpor by pyruvate in obese mice relies on adenosine signaling and is accompanied by changes in brain levels of hexose bisphosphate and GABA as detected by mass spectroscopy-based imaging. Pyruvate does not induce torpor in lean mice but results in the activation of brown adipose tissue (BAT) with an increase in the level of uncoupling protein-1 (UCP1). Denervation of BAT in lean mice blocks this increase in UCP1 and allows the pyruvate-induced torpor phenotype. Thus, pyruvate administration induces torpor in obese mice by pathways involving adenosine and GABA signaling and a failure of normal activation of BAT.}, } @article {pmid29311302, year = {2018}, author = {Goncalves, MD and Hwang, SK and Pauli, C and Murphy, CJ and Cheng, Z and Hopkins, BD and Wu, D and Loughran, RM and Emerling, BM and Zhang, G and Fearon, DT and Cantley, LC}, title = {Fenofibrate prevents skeletal muscle loss in mice with lung cancer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E743-E752}, pmid = {29311302}, issn = {1091-6490}, support = {P30 CA045508/CA/NCI NIH HHS/United States ; R35 CA197588/CA/NCI NIH HHS/United States ; U54 CA210184/CA/NCI NIH HHS/United States ; }, mesh = {Amino Acids/metabolism ; Animals ; Cachexia/blood/etiology/*prevention & control ; Carcinoma, Non-Small-Cell Lung/*complications ; Drug Evaluation, Preclinical ; Fenofibrate/pharmacology/*therapeutic use ; Gluconeogenesis ; Ketone Bodies/deficiency ; Lipid Metabolism/drug effects ; Liver/drug effects/metabolism ; Lung Neoplasms/*complications ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice ; Muscle, Skeletal/drug effects/metabolism/pathology ; PPAR gamma/*agonists/metabolism ; }, abstract = {The cancer anorexia cachexia syndrome is a systemic metabolic disorder characterized by the catabolism of stored nutrients in skeletal muscle and adipose tissue that is particularly prevalent in nonsmall cell lung cancer (NSCLC). Loss of skeletal muscle results in functional impairments and increased mortality. The aim of the present study was to characterize the changes in systemic metabolism in a genetically engineered mouse model of NSCLC. We show that a portion of these animals develop loss of skeletal muscle, loss of adipose tissue, and increased inflammatory markers mirroring the human cachexia syndrome. Using noncachexic and fasted animals as controls, we report a unique cachexia metabolite phenotype that includes the loss of peroxisome proliferator-activated receptor-α (PPARα) -dependent ketone production by the liver. In this setting, glucocorticoid levels rise and correlate with skeletal muscle degradation and hepatic markers of gluconeogenesis. Restoring ketone production using the PPARα agonist, fenofibrate, prevents the loss of skeletal muscle mass and body weight. These results demonstrate how targeting hepatic metabolism can prevent muscle wasting in lung cancer, and provide evidence for a therapeutic strategy.}, } @article {pmid29311301, year = {2018}, author = {Dutta Banik, D and Martin, LE and Freichel, M and Torregrossa, AM and Medler, KF}, title = {TRPM4 and TRPM5 are both required for normal signaling in taste receptor cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E772-E781}, pmid = {29311301}, issn = {1091-6490}, mesh = {Animals ; Calcium/metabolism ; Endoplasmic Reticulum/metabolism ; Food Preferences ; Male ; Mice, Inbred C57BL ; Mice, Knockout ; Phospholipase C beta/metabolism ; Sodium/metabolism ; TRPM Cation Channels/*metabolism ; Taste Buds/*metabolism ; }, abstract = {Peripheral taste receptor cells use multiple signaling pathways to transduce taste stimuli into output signals that are sent to the brain. Transient receptor potential melastatin 5 (TRPM5), a sodium-selective TRP channel, functions as a common downstream component in sweet, bitter, and umami signaling pathways. In the absence of TRPM5, mice have a reduced, but not abolished, ability to detect stimuli, suggesting that a TRPM5-independent pathway also contributes to these signals. Here, we identify a critical role for the sodium-selective TRP channel TRPM4 in taste transduction. Using live cell imaging and behavioral studies in KO mice, we show that TRPM4 and TRPM5 are both involved in taste-evoked signaling. Loss of either channel significantly impairs taste, and loss of both channels completely abolishes the ability to detect bitter, sweet, or umami stimuli. Thus, both TRPM4 and TRPM5 are required for transduction of taste stimuli.}, } @article {pmid29311300, year = {2018}, author = {}, title = {Correction for Liu et al., Earliest hydraulic enterprise in China, 5,100 years ago.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E841}, doi = {10.1073/pnas.1722309115}, pmid = {29311300}, issn = {1091-6490}, } @article {pmid29311299, year = {2018}, author = {Goldenberg, A and Cohen-Chen, S and Goyer, JP and Dweck, CS and Gross, JJ and Halperin, E}, title = {Testing the impact and durability of a group malleability intervention in the context of the Israeli-Palestinian conflict.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {696-701}, pmid = {29311299}, issn = {1091-6490}, mesh = {Arabs ; Attitude ; Conflict (Psychology) ; Ethnic Groups/*psychology ; Female ; Humans ; Israel ; Jews ; Male ; Negotiating/*psychology ; Peer Group ; *Peer Influence ; Violence/prevention & control/psychology ; Warfare ; }, abstract = {Fostering perceptions of group malleability (teaching people that groups are capable of change and improvement) has been shown to lead to short-term improvements in intergroup attitudes and willingness to make concessions in intractable conflicts. The present study, a field intervention involving 508 Israelis from three locations in Israel, replicated and substantially extended those findings by testing the durability of a group malleability intervention during a 6-month period of frequent violence. Three different 5-hour-long interventions were administered as leadership workshops. The group malleability intervention was compared with a neutral coping intervention and, importantly, with a state-of-the-art perspective-taking intervention. The group malleability intervention proved superior to the coping intervention in improving attitudes, hope, and willingness to make concessions, and maintained this advantage during a 6-month period of intense intergroup conflict. Moreover, it was as good as, and in some respects superior to, the perspective-taking intervention. These findings provide a naturalistic examination of the potential of group malleability interventions to increase openness to conflict resolution.}, } @article {pmid29311298, year = {2018}, author = {Song, NY and Zhu, F and Wang, Z and Willette-Brown, J and Xi, S and Sun, Z and Su, L and Wu, X and Ma, B and Nussinov, R and Xia, X and Schrump, DS and Johnson, PF and Karin, M and Hu, Y}, title = {IKKα inactivation promotes Kras-initiated lung adenocarcinoma development through disrupting major redox regulatory pathways.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E812-E821}, pmid = {29311298}, issn = {1091-6490}, support = {ZIA BC011212/BC/NCI NIH HHS/United States ; ZIA BC011391/BC/NCI NIH HHS/United States ; P42 ES010337/ES/NIEHS NIH HHS/United States ; R01 CA163798/CA/NCI NIH HHS/United States ; HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; }, mesh = {Acetophenones ; Acetylcysteine ; Adenocarcinoma/*genetics/metabolism ; Animals ; Cell Proliferation ; Cellular Senescence ; Cyclin-Dependent Kinase Inhibitor p21/metabolism ; Epigenesis, Genetic ; Humans ; I-kappa B Kinase/*physiology ; Lung Neoplasms/*genetics/metabolism ; Mice ; NADPH Oxidase 2/metabolism ; NF-E2-Related Factor 2/metabolism ; Proto-Oncogene Proteins p21(ras)/metabolism ; Reactive Oxygen Species/metabolism ; Tumor Suppressor Protein p53/metabolism ; }, abstract = {Lung adenocarcinoma (ADC) and squamous cell carcinoma (SCC) are two distinct and predominant types of human lung cancer. IκB kinase α (IKKα) has been shown to suppress lung SCC development, but its role in ADC is unknown. We found inactivating mutations and homologous or hemizygous deletions in the CHUK locus, which encodes IKKα, in human lung ADCs. The CHUK deletions significantly reduced the survival time of patients with lung ADCs harboring KRAS mutations. In mice, lung-specific Ikkα ablation (IkkαΔLu) induces spontaneous ADCs and promotes KrasG12D-initiated ADC development, accompanied by increased cell proliferation, decreased cell senescence, and reactive oxygen species (ROS) accumulation. IKKα deletion up-regulates NOX2 and down-regulates NRF2, leading to ROS accumulation and blockade of cell senescence induction, which together accelerate ADC development. Pharmacologic inhibition of NADPH oxidase or ROS impairs KrasG12D-mediated ADC development in IkkαΔLu mice. Therefore, IKKα modulates lung ADC development by controlling redox regulatory pathways. This study demonstrates that IKKα functions as a suppressor of lung ADC in human and mice through a unique mechanism that regulates tumor cell-associated ROS metabolism.}, } @article {pmid29311297, year = {2018}, author = {Kandratsenka, A and Jiang, H and Dorenkamp, Y and Janke, SM and Kammler, M and Wodtke, AM and Bünermann, O}, title = {Unified description of H-atom-induced chemicurrents and inelastic scattering.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {680-684}, pmid = {29311297}, issn = {1091-6490}, abstract = {The Born-Oppenheimer approximation (BOA) provides the foundation for virtually all computational studies of chemical binding and reactivity, and it is the justification for the widely used "balls and springs" picture of molecules. The BOA assumes that nuclei effectively stand still on the timescale of electronic motion, due to their large masses relative to electrons. This implies electrons never change their energy quantum state. When molecules react, atoms must move, meaning that electrons may become excited in violation of the BOA. Such electronic excitation is clearly seen for: (i) Schottky diodes where H adsorption at Ag surfaces produces electrical "chemicurrent;" (ii) Au-based metal-insulator-metal (MIM) devices, where chemicurrents arise from H-H surface recombination; and (iii) Inelastic energy transfer, where H collisions with Au surfaces show H-atom translation excites the metal's electrons. As part of this work, we report isotopically selective hydrogen/deuterium (H/D) translational inelasticity measurements in collisions with Ag and Au. Together, these experiments provide an opportunity to test new theories that simultaneously describe both nuclear and electronic motion, a standing challenge to the field. Here, we show results of a recently developed first-principles theory that quantitatively explains both inelastic scattering experiments that probe nuclear motion and chemicurrent experiments that probe electronic excitation. The theory explains the magnitude of chemicurrents on Ag Schottky diodes and resolves an apparent paradox--chemicurrents exhibit a much larger isotope effect than does H/D inelastic scattering. It also explains why, unlike Ag-based Schottky diodes, Au-based MIM devices are insensitive to H adsorption.}, } @article {pmid29311296, year = {2018}, author = {Kristensen, DM and Desdoits-Lethimonier, C and Mackey, AL and Dalgaard, MD and De Masi, F and Munkbøl, CH and Styrishave, B and Antignac, JP and Le Bizec, B and Platel, C and Hay-Schmidt, A and Jensen, TK and Lesné, L and Mazaud-Guittot, S and Kristiansen, K and Brunak, S and Kjaer, M and Juul, A and Jégou, B}, title = {Ibuprofen alters human testicular physiology to produce a state of compensated hypogonadism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E715-E724}, pmid = {29311296}, issn = {1091-6490}, mesh = {Adult ; Analgesics, Non-Narcotic/*adverse effects/blood ; Cell Line ; Gene Expression/drug effects ; Humans ; Hypogonadism/blood/*chemically induced ; Ibuprofen/*adverse effects/blood ; In Vitro Techniques ; Leydig Cells/drug effects/metabolism ; Luteinizing Hormone/*blood ; Male ; Middle Aged ; Prostaglandins/biosynthesis ; Sertoli Cells/drug effects ; Testosterone/*blood ; }, abstract = {Concern has been raised over increased male reproductive disorders in the Western world, and the disruption of male endocrinology has been suggested to play a central role. Several studies have shown that mild analgesics exposure during fetal life is associated with antiandrogenic effects and congenital malformations, but the effects on the adult man remain largely unknown. Through a clinical trial with young men exposed to ibuprofen, we show that the analgesic resulted in the clinical condition named "compensated hypogonadism," a condition prevalent among elderly men and associated with reproductive and physical disorders. In the men, luteinizing hormone (LH) and ibuprofen plasma levels were positively correlated, and the testosterone/LH ratio decreased. Using adult testis explants exposed or not exposed to ibuprofen, we demonstrate that the endocrine capabilities from testicular Leydig and Sertoli cells, including testosterone production, were suppressed through transcriptional repression. This effect was also observed in a human steroidogenic cell line. Our data demonstrate that ibuprofen alters the endocrine system via selective transcriptional repression in the human testes, thereby inducing compensated hypogonadism.}, } @article {pmid29311295, year = {2018}, author = {Vavvas, DG and Small, KW and Awh, CC and Zanke, BW and Tibshirani, RJ and Kustra, R}, title = {CFH and ARMS2 genetic risk determines progression to neovascular age-related macular degeneration after antioxidant and zinc supplementation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E696-E704}, pmid = {29311295}, issn = {1091-6490}, mesh = {Antioxidants/*therapeutic use ; Complement Factor H/genetics ; Disease Progression ; Humans ; Macular Degeneration/*genetics/*prevention & control ; Proteins/*genetics ; Zinc/*therapeutic use ; }, abstract = {We evaluated the influence of an antioxidant and zinc nutritional supplement [the Age-Related Eye Disease Study (AREDS) formulation] on delaying or preventing progression to neovascular AMD (NV) in persons with age-related macular degeneration (AMD). AREDS subjects (n = 802) with category 3 or 4 AMD at baseline who had been treated with placebo or the AREDS formulation were evaluated for differences in the risk of progression to NV as a function of complement factor H (CFH) and age-related maculopathy susceptibility 2 (ARMS2) genotype groups. We used published genetic grouping: a two-SNP haplotype risk-calling algorithm to assess CFH, and either the single SNP rs10490924 or 372_815del443ins54 to mark ARMS2 risk. Progression risk was determined using the Cox proportional hazard model. Genetics-treatment interaction on NV risk was assessed using a multiiterative bootstrap validation analysis. We identified strong interaction of genetics with AREDS formulation treatment on the development of NV. Individuals with high CFH and no ARMS2 risk alleles and taking the AREDS formulation had increased progression to NV compared with placebo. Those with low CFH risk and high ARMS2 risk had decreased progression risk. Analysis of CFH and ARMS2 genotype groups from a validation dataset reinforces this conclusion. Bootstrapping analysis confirms the presence of a genetics-treatment interaction and suggests that individual treatment response to the AREDS formulation is largely determined by genetics. The AREDS formulation modifies the risk of progression to NV based on individual genetics. Its use should be based on patient-specific genotype.}, } @article {pmid29311294, year = {2018}, author = {Liu, CP and Tsai, TI and Cheng, T and Shivatare, VS and Wu, CY and Wu, CY and Wong, CH}, title = {Glycoengineering of antibody (Herceptin) through yeast expression and in vitro enzymatic glycosylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {720-725}, pmid = {29311294}, issn = {1091-6490}, mesh = {Antibodies, Monoclonal/metabolism ; Antibody-Dependent Cell Cytotoxicity/physiology ; Glycoproteins/metabolism/*pharmacology ; Glycoside Hydrolases/*metabolism/pharmacology ; Glycosylation ; Humans ; Pichia/metabolism ; Polysaccharides/metabolism ; Saccharomyces cerevisiae/metabolism ; Trastuzumab/*chemistry/metabolism ; }, abstract = {Monoclonal antibodies (mAbs) have been developed as therapeutics, especially for the treatment of cancer, inflammation, and infectious diseases. Because the glycosylation of mAbs in the Fc region influences their interaction with effector cells that kill antibody-targeted cells, and the current method of antibody production is relatively expensive, efforts have been directed toward the development of alternative expressing systems capable of large-scale production of mAbs with desirable glycoforms. In this study, we demonstrate that the mAb trastuzumab expressed in glycoengineered P. pastoris can be remodeled through deglycosylation by endoglycosidases identified from the Carbohydrate Active Enzymes database and through transglycosylation using glycans with a stable leaving group to generate a homogeneous antibody designed to optimize the effector functions. The 10 newly identified recombinant bacterial endoglycosidases are complementary to existing endoglycosidases (EndoA, EndoH, EndoS), two of which can even accept sialylated tri- and tetraantennary glycans as substrates.}, } @article {pmid29311293, year = {2018}, author = {Bansal, A and Molina-Cruz, A and Brzostowski, J and Liu, P and Luo, Y and Gunalan, K and Li, Y and Ribeiro, JMC and Miller, LH}, title = {PfCDPK1 is critical for malaria parasite gametogenesis and mosquito infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {774-779}, pmid = {29311293}, issn = {1091-6490}, mesh = {Animals ; CRISPR-Cas Systems ; Culicidae/*parasitology ; *Gametogenesis ; Gene Editing ; Gene Expression Regulation ; Plasmodium falciparum ; Protein Kinases/*physiology ; Protozoan Proteins/*physiology ; }, abstract = {Efforts to knock out Plasmodium falciparum calcium-dependent protein kinase 1 (PfCDPK1) from asexual erythrocytic stage have not been successful, indicating an indispensable role of the enzyme in asexual growth. We recently reported generation of a transgenic parasite with mutant CDPK1 [Bansal A, et al. (2016) MBio 7:e02011-16]. The mutant CDPK1 (T145M) had reduced activity of transphosphorylation. We reasoned that CDPK1 could be disrupted in the mutant parasites. Consistent with this assumption, CDPK1 was successfully disrupted in the mutant parasites using CRISPR/Cas9. We and others could not disrupt PfCDPK1 in the WT parasites. The CDPK1 KO parasites show a slow growth rate compared with the WT and the CDPK1 T145M parasites. Additionally, the CDPK1 KO parasites show a defect in both male and female gametogenesis and could not establish an infection in mosquitoes. Complementation of the KO parasite with full-length PfCDPK1 partially rescued the asexual growth defect and mosquito infection. Comparative global transcriptomics of WT and the CDPK1 KO schizonts using RNA-seq show significantly high transcript expression of gametocyte-specific genes in the CDPK1 KO parasites. This study conclusively demonstrates that CDPK1 is a good target for developing transmission-blocking drugs.}, } @article {pmid29311292, year = {2018}, author = {}, title = {Retraction for Chanmanee et al., Solar photothermochemical alkane reverse combustion.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E557}, doi = {10.1073/pnas.1721878115}, pmid = {29311292}, issn = {1091-6490}, } @article {pmid29311031, year = {2018}, author = {}, title = {Stephanie Thomas: Modeling Disease Transmission in a Changing World.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {173-174}, doi = {10.1016/j.pt.2017.12.005}, pmid = {29311031}, issn = {1471-5007}, mesh = {Animals ; Arbovirus Infections/*prevention & control/*transmission ; Environment ; Humans ; Introduced Species ; *Models, Biological ; Mosquito Vectors/*virology ; }, } @article {pmid29310721, year = {2018}, author = {Bruinsma, FJ and Joo, JE and Wong, EM and Giles, GG and Southey, MC}, title = {The utility of DNA extracted from saliva for genome-wide molecular research platforms.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {8}, pmid = {29310721}, issn = {1756-0500}, support = {APP1061177//National Health and Medical Research Council/ ; 1074383//National Health and Medical Research Council/ ; 623204//National Health and Medical Research Council/ ; 1011626//National Health and Medical Research Council/ ; }, mesh = {Blood/*metabolism ; *DNA Methylation ; *Epigenesis, Genetic ; High-Throughput Nucleotide Sequencing/*standards ; Humans ; Saliva/*metabolism ; Sequence Analysis, DNA/*standards ; }, abstract = {OBJECTIVE: The study aimed to investigate the suitability of DNA extracted from saliva for high throughput molecular genotyping and DNA methylation platforms by comparing its performance with that of DNA extracted from blood. The genome-wide methylation profile, using the Infinium HumanMethylation450 Beadchip array® (Illumina, San Diego, CA), was measured for 20 DNA samples. Common genetic variation was measured, using the Infinium HumanCore Beadchip® (Illumina, San Diego, CA) for 4 samples (matching samples from 2 people).

RESULTS: DNA from blood and saliva returned genotyping call rates and reproducibility frequencies of > 99%. High-quality DNA methylation data was obtained from both saliva and blood DNA, with average detection p-values for each sample ranging from 0.001 to 0.006. Slightly higher global DNA methylation levels were observed in whole blood DNA than saliva DNA. Correlations between individuals for each sample type were generally greater than correlations between two sample types from the same individual (Pearson's correlation, r = 0.9696 in 10 pairs of matched blood and saliva derived DNA, r = 0.9702 between saliva samples, and r = 0.9769 between blood derived DNA). Saliva yields DNA of sufficient quantity and quality to compare favourably with blood as a source of DNA for genetic and epigenetic research purposes.}, } @article {pmid29310715, year = {2018}, author = {Bisconti, R and Tenchini, R and Belfiore, C and Nascetti, G and Canestrelli, D}, title = {Fast and accurate identification of cryptic and sympatric mayfly species of the Baetis rhodani group.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {7}, pmid = {29310715}, issn = {1756-0500}, mesh = {Animals ; Ephemeroptera/*classification/genetics ; Mediterranean Islands ; Polymerase Chain Reaction ; }, abstract = {OBJECTIVE: Species of the Baetis rhodani group are among the most widespread mayflies of the Palearctic region. However, frequent occurrence of morphologically cryptic species complicates the identification of sympatric species. Here, we proposed and tested a method for the fast, accurate, and cost-effective assignment of a large number of individuals to their putative species, based on high resolution melting profiles of a standard mitochondrial gene fragment. We tested this method using a system of three recently identified cryptic species inhabiting the Tyrrhenian Islands (western Mediterranean basin).

RESULTS: Highly species-specific high resolution melting profiles were obtained, allowing the unequivocal attribution of each individual to the respective species. This assay provides a convenient and easily customizable alternative to traditional barcoding approaches, provided that the mayfly taxa occurring within the geographic area of interest have been previously identified and their high resolution melting profiles assessed.}, } @article {pmid29310713, year = {2018}, author = {Maire, J and Vincent-Monégat, C and Masson, F and Zaidman-Rémy, A and Heddi, A}, title = {An IMD-like pathway mediates both endosymbiont control and host immunity in the cereal weevil Sitophilus spp.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {6}, pmid = {29310713}, issn = {2049-2618}, support = {ANR-13-BSV7-0016-01//ANR/International ; }, mesh = {Animals ; Antimicrobial Cationic Peptides/*metabolism ; Bacterial Proteins/metabolism ; Cytotoxins/adverse effects ; Edible Grain/*parasitology ; Enterobacteriaceae/*metabolism ; Gene Expression Regulation ; Host Specificity ; Host-Pathogen Interactions ; Immunity, Innate ; Insect Proteins/*genetics/metabolism ; Symbiosis ; Transcription Factors/genetics/metabolism ; Weevils/*genetics/immunology/microbiology ; }, abstract = {Many insects developing on nutritionally unbalanced diets have evolved symbiotic associations with vertically transmitted intracellular bacteria (endosymbionts) that provide them with metabolic components, thereby improving the host's abilities to thrive on such poor ecological niches. While host-endosymbiont coevolutionary constraints are known to entail massive genomic changes in the microbial partner, host's genomic evolution remains elusive, particularly with regard to the immune system. In the cereal weevil Sitophilus spp., which houses Sodalis pierantonius, endosymbionts are secluded in specialized host cells, the bacteriocytes that group together as an organ, the bacteriome. We previously reported that at standard conditions, the bacteriome highly expresses the coleoptericin A (colA) antimicrobial peptide (AMP), which was shown to prevent endosymbiont escape from the bacteriocytes. However, following the insect systemic infection by pathogens, the bacteriome upregulates a cocktail of AMP encoding genes, including colA. The regulations that allow these contrasted immune responses remain unknown. In this short report, we provide evidence that an IMD-like pathway is conserved in two sibling species of cereal weevils, Sitophilus oryzae and Sitophilus zeamais. RNA interference (RNAi) experiments showed that imd and relish genes are essential for (i) colA expression in the bacteriome under standard conditions, (ii) AMP up-regulation in the bacteriome following a systemic immune challenge, and (iii) AMP systemic induction following an immune challenge. Histological analyses also showed that relish inhibition by RNAi resulted in endosymbiont escape from the bacteriome, strengthening the involvement of an IMD-like pathway in endosymbiont control. We conclude that Sitophilus' IMD-like pathway mediates both the bacteriome immune program involved in endosymbiont seclusion within the bacteriocytes and the systemic and local immune responses to exogenous challenges. This work provides a striking example of how a conserved immune pathway, initially described as essential in pathogen clearance, also functions in the control of mutualistic associations.}, } @article {pmid29310708, year = {2018}, author = {Walsh, E and Sahm, LJ and Kearney, PM and Smithson, H and Kerins, DM and Ngwa, C and Fitzgerald, C and Mc Carthy, S and Connolly, E and Dalton, K and Byrne, D and Carey, M and Bradley, C}, title = {The PHARMS (Patient Held Active Record of Medication Status) feasibility study: a research proposal.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {6}, pmid = {29310708}, issn = {1756-0500}, mesh = {Aged ; *Electronic Health Records ; Feasibility Studies ; Female ; Health Services Research ; Humans ; Male ; Medication Reconciliation/*methods/*standards ; *Outcome and Process Assessment (Health Care) ; Patient Admission/*standards ; Patient Discharge/*standards ; Primary Health Care/*standards ; Qualitative Research ; Secondary Care/*standards ; Transitional Care/*standards ; }, abstract = {OBJECTIVE: Medication errors are a major source of preventable morbidity, mortality and cost and many occur at the times of hospital admission and discharge. Novel interventions (such as new methods of recording medication information and conducting medication reconciliation) are required to facilitate accurate transfer of medication information. With existing evidence supporting the use of information technology and the patient representing the one constant in the care process, an electronic patient held medication record may provide a solution. This study will assess the feasibility of introducing a patient held electronic medication record in primary and secondary care using the Consolidated Framework for Implementation Research (CFIR).This feasibility study is a mixed method study of community dwelling older adult patients admitted to an urban secondary care facility comprising a non-randomised intervention and qualitative interviews with key stakeholders. Outcomes of interest include clinical outcomes and process evaluation.This study will yield insights pertaining to feasibility, acceptability and participation for a more definitive evaluation of the intervention. The study also has the potential to contribute to knowledge of implementation of technology in a healthcare context and to the broader area of implementation science.}, } @article {pmid29310707, year = {2018}, author = {Gayathri, M and Shirasawa, K and Varshney, RK and Pandey, MK and Bhat, RS}, title = {Development of AhMITE1 markers through genome-wide analysis in peanut (Arachis hypogaea L.).}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {10}, pmid = {29310707}, issn = {1756-0500}, mesh = {Arachis/*genetics ; DNA, Plant/*genetics ; Genetic Markers/*genetics ; Genome, Plant/*genetics ; Polymorphism, Genetic/*genetics ; Sequence Analysis, DNA/*methods ; }, abstract = {OBJECTIVE: In peanut, the DNA polymorphism is very low despite enormous phenotypic variations. This limits the use of genomics-assisted breeding to enhance peanut productivity. This study aimed to develop and validate new AhMITE1 and cleaved amplified polymorphic sequences (CAPS) markers.

RESULTS: In total, 2957 new AhMITE1 markers were developed in addition to identifying 465 already reported markers from the whole genome re-sequencing data (WGRS) of 33 diverse genotypes of peanut. The B sub-genome (1620) showed more number of markers than the A sub-genome (1337). Distribution also varied among the chromosomes of both the sub-genomes. Further, 52.6% of the markers were from genic regions; where 31.0% were from intronic regions and 5.2% were from exonic regions. Of the 343 randomly selected markers, 82.2% showed amplification validation, with up to 35.5% polymorphism. From the SNPs on the A03, B01, B02 and B03 chromosomes, 11,730 snip-SNPs (potential CAPS sites) were identified, and 500 CAPS markers were developed from chromosome A03. Of these markers, 30.0% showed validation and high polymorphism. This study demonstrated the potential of the WGRS data to develop AhMITE1 and CAPS markers, which showed high level of validation and polymorphism. These marker resources will be useful for various genetic studies and mapping in peanut.}, } @article {pmid29310699, year = {2018}, author = {Kumyaito, N and Yupapin, P and Tamee, K}, title = {Planning a sports training program using Adaptive Particle Swarm Optimization with emphasis on physiological constraints.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {9}, pmid = {29310699}, issn = {1756-0500}, mesh = {Adult ; Athletic Performance/*physiology ; Bicycling/*physiology ; Exercise/*physiology ; Humans ; Male ; *Models, Theoretical ; *Practice (Psychology) ; }, abstract = {OBJECTIVE: An effective training plan is an important factor in sports training to enhance athletic performance. A poorly considered training plan may result in injury to the athlete, and overtraining. Good training plans normally require expert input, which may have a cost too great for many athletes, particularly amateur athletes. The objectives of this research were to create a practical cycling training plan that substantially improves athletic performance while satisfying essential physiological constraints. Adaptive Particle Swarm Optimization using ɛ-constraint methods were used to formulate such a plan and simulate the likely performance outcomes. The physiological constraints considered in this study were monotony, chronic training load ramp rate and daily training impulse.

RESULTS: A comparison of results from our simulations against a training plan from British Cycling, which we used as our standard, showed that our training plan outperformed the benchmark in terms of both athletic performance and satisfying all physiological constraints.}, } @article {pmid29310696, year = {2018}, author = {Christen, JR and Edmond, E and Drancourt, M}, title = {Methods for detecting Gemmata spp. bacteremia in the microbiology laboratory.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {11}, pmid = {29310696}, issn = {1756-0500}, mesh = {Bacteremia/*blood/*microbiology ; Humans ; Planctomycetales/*isolation & purification ; Real-Time Polymerase Chain Reaction ; }, abstract = {OBJECTIVE: Gemmata bacteria are fastidious, Gram-negative and aerobic. The only representatives are Gemmata obscuriglobus and Gemmata massiliana. These Planctomycetes appear to be a part of human digestive tract microbiome, and G. massiliana has been isolated from water. Further specific detection in the blood of two patients with febrile neutropenia suggests that Gemmata bacteremia may remain under-documented. The objective of this study was to develop an effective protocol to document Gemmata spp. bacteremia in the laboratory. Using mock-infected and control blood specimens, three methods for detecting Gemmata bacteremia, namely, automated microbial detection, culture on solid medium, and quantitative polymerase chain reaction (PCR), have been developed and studied.

RESULTS: Gemmata spp. were undetected by automated blood culture system but culturing mock-infected blood on Caulobacter agar detected ≥ 102 G. obscuriglobus bacteria/mL and ≥ 104 G. massiliana bacteria/mL. Specific real-time PCR detected 102 Gemmata bacteria/mL. These protocols may be used to investigate the epidemiology of Gemmata spp. bacteremia.}, } @article {pmid29310597, year = {2018}, author = {Carruthers, M and Yurchenko, AA and Augley, JJ and Adams, CE and Herzyk, P and Elmer, KR}, title = {De novo transcriptome assembly, annotation and comparison of four ecological and evolutionary model salmonid fish species.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {32}, pmid = {29310597}, issn = {1471-2164}, support = {//Wellcome Trust/United Kingdom ; BB/J013854/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; CIG-321999//FP7 People: Marie-Curie Actions/International ; 097821/Z/11/Z//Wellcome Trust/United Kingdom ; }, abstract = {BACKGROUND: Salmonid fishes exhibit high levels of phenotypic and ecological variation and are thus ideal model systems for studying evolutionary processes of adaptive divergence and speciation. Furthermore, salmonids are of major interest in fisheries, aquaculture, and conservation research. Improving understanding of the genetic mechanisms underlying traits in these species would significantly progress research in these fields. Here we generate high quality de novo transcriptomes for four salmonid species: Atlantic salmon (Salmo salar), brown trout (Salmo trutta), Arctic charr (Salvelinus alpinus), and European whitefish (Coregonus lavaretus). All species except Atlantic salmon have no reference genome publicly available and few if any genomic studies to date.

RESULTS: We used paired-end RNA-seq on Illumina to generate high coverage sequencing of multiple individuals, yielding between 180 and 210 M reads per species. After initial assembly, strict filtering was used to remove duplicated, redundant, and low confidence transcripts. The final assemblies consisted of 36,505 protein-coding transcripts for Atlantic salmon, 35,736 for brown trout, 33,126 for Arctic charr, and 33,697 for European whitefish and are made publicly available. Assembly completeness was assessed using three approaches, all of which supported high quality of the assemblies: 1) ~78% of Actinopterygian single-copy orthologs were successfully captured in our assemblies, 2) orthogroup inference identified high overlap in the protein sequences present across all four species (40% shared across all four and 84% shared by at least two), and 3) comparison with the published Atlantic salmon genome suggests that our assemblies represent well covered (~98%) protein-coding transcriptomes. Thorough comparison of the generated assemblies found that 84-90% of transcripts in each assembly were orthologous with at least one of the other three species. We also identified 34-37% of transcripts in each assembly as paralogs. We further compare completeness and annotation statistics of our new assemblies to available related species.

CONCLUSION: New, high-confidence protein-coding transcriptomes were generated for four ecologically and economically important species of salmonids. This offers a high quality pipeline for such complex genomes, represents a valuable contribution to the existing genomic resources for these species and provides robust tools for future investigation of gene expression and sequence evolution in these and other salmonid species.}, } @article {pmid29310588, year = {2018}, author = {Purcell, CM and Seetharam, AS and Snodgrass, O and Ortega-García, S and Hyde, JR and Severin, AJ}, title = {Insights into teleost sex determination from the Seriola dorsalis genome assembly.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {31}, pmid = {29310588}, issn = {1471-2164}, support = {Office of Aquaculture, ICAF Program//National Oceanic and Atmospheric Administration/International ; Saltonstall Kennedy 15WCR013//National Oceanic and Atmospheric Administration/International ; MCB140217//XSEDE/International ; }, mesh = {Animals ; Binding Sites ; Computational Biology/methods ; Databases, Genetic ; Fishes/*genetics/metabolism ; Genetic Markers ; *Genome ; Genome-Wide Association Study ; *Genomics/methods ; INDEL Mutation ; Molecular Sequence Annotation ; Nucleotide Motifs ; Protein Binding ; Sex Determination Processes/*genetics ; Transcription Factors ; }, abstract = {BACKGROUND: The assembly and annotation of a genome is a valuable resource for a species, with applications ranging from conservation genomics to gene discovery. Genomic resource development is especially important for species in culture, such as the California Yellowtail (Seriola dorsalis), the likely candidate for the establishment of commercial offshore aquaculture production in southern California. Genomic resource development for this species will improve the understanding of sex and other phenotypic traits, and allow for rapid increases in genetic improvement for and economic gain in culture production.

RESULTS: We describe the assembly and annotation of the S. dorsalis genome, and present resequencing data from 45 male and 45 female wild-caught S. dorsalis used to identify a sex-determining region and marker in this species. The genome assembly captured approximately 93% of the total 685 MB genome with an average coverage depth of 180×. Using the assembled genome, resequencing data from the 90 fish were aligned to place boundaries on the sex-determining region. Sex-specific markers were developed based on a female-specific, 61 nucleotide deletion identified in that region. We hypothesize that Estradiol 17-beta-dehydrogenase is the putative sex-determining gene and propose a plausible genetic mechanism for ZW sex determination in S. dorsalis involving a female-specific deletion of a transcription factor binding motif that may be targeted by Sox3.

CONCLUSIONS: Understanding the mechanism of sex determination and development of assays to determine sex is critical both for management of wild fisheries and for development of efficient and sustainable aquaculture practices. In addition, this genome assembly for S. dorsalis will be a substantial resource for a variety of future research applications.}, } @article {pmid29310587, year = {2018}, author = {MacConaill, LE and Burns, RT and Nag, A and Coleman, HA and Slevin, MK and Giorda, K and Light, M and Lai, K and Jarosz, M and McNeill, MS and Ducar, MD and Meyerson, M and Thorner, AR}, title = {Unique, dual-indexed sequencing adapters with UMIs effectively eliminate index cross-talk and significantly improve sensitivity of massively parallel sequencing.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {30}, pmid = {29310587}, issn = {1471-2164}, mesh = {Computational Biology/*methods ; *High-Throughput Nucleotide Sequencing/methods/standards ; Humans ; Sensitivity and Specificity ; *Sequence Analysis, DNA/methods/standards ; }, abstract = {BACKGROUND: Sample index cross-talk can result in false positive calls when massively parallel sequencing (MPS) is used for sensitive applications such as low-frequency somatic variant discovery, ancient DNA investigations, microbial detection in human samples, or circulating cell-free tumor DNA (ctDNA) variant detection. Therefore, the limit-of-detection of an MPS assay is directly related to the degree of index cross-talk.

RESULTS: Cross-talk rates up to 0.29% were observed when using standard, combinatorial adapters, resulting in 110,180 (0.1% cross-talk rate) or 1,121,074 (0.29% cross-talk rate) misassigned reads per lane in non-patterned and patterned Illumina flow cells, respectively. Here, we demonstrate that using unique, dual-matched indexed adapters dramatically reduces index cross-talk to ≤1 misassigned reads per flow cell lane. While the current study was performed using dual-matched indices, using unique, dual-unrelated indices would also be an effective alternative.

CONCLUSIONS: For sensitive downstream analyses, the use of combinatorial indices for multiplexed hybrid capture and sequencing is inappropriate, as it results in an unacceptable number of misassigned reads. Cross-talk can be virtually eliminated using dual-matched indexed adapters. These results suggest that use of such adapters is critical to reduce false positive rates in assays that aim to identify low allele frequency events, and strongly indicate that dual-matched adapters be implemented for all sensitive MPS applications.}, } @article {pmid29310584, year = {2018}, author = {Pan, T and Lin, L and Wang, J and Liu, Q and Wei, C}, title = {Long branch-chains of amylopectin with B-type crystallinity in rice seed with inhibition of starch branching enzyme I and IIb resist in situ degradation and inhibit plant growth during seedling development : Degradation of rice starch with inhibition of SBEI/IIb during seedling development.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {9}, pmid = {29310584}, issn = {1471-2229}, support = {31270221//National Natural Science Foundation of China/International ; BK20160457//Natural Science Foundation of Jiangsu Province/International ; }, mesh = {1,4-alpha-Glucan Branching Enzyme/genetics/metabolism ; Amylopectin/*metabolism ; Oryza/genetics/growth & development/*metabolism ; Plant Proteins/genetics/metabolism ; Seedlings/growth & development/*metabolism ; }, abstract = {BACKGROUND: Endosperm starch provides prime energy for cereal seedling growth. Cereal endosperm with repression of starch branching enzyme (SBE) has been widely studied for its high resistant starch content and health benefit. However, in barley and maize, the repression of SBE changes starch component and amylopectin structure which affects grain germination and seedling establishment. A high resistant starch rice line (TRS) has been developed through inhibiting SBEI/IIb, and its starch has very high resistance to in vitro hydrolysis and digestion. However, it is unclear whether the starch resists in situ degradation in seed and influences seedling growth after grain germination.

RESULTS: In this study, TRS and its wild-type rice cultivar Te-qing (TQ) were used to investigate the seedling growth, starch property changes, and in situ starch degradation during seedling growth. The slow degradation of starch in TRS seed restrained the seedling growth. The starch components including amylose and amylopectin were simultaneously degraded in TQ seeds during seedling growth, but in TRS seeds, the amylose was degraded faster than amylopectin and the amylopectin long branch-chains with B-type crystallinity had high resistance to in situ degradation. TQ starch was gradually degraded from the proximal to distal region of embryo and from the outer to inner in endosperm. However, TRS endosperm contained polygonal, aggregate, elongated and hollow starch from inner to outer. The polygonal starch similar to TQ starch was completely degraded, and the other starches with long branch-chains of amylopectin and B-type crystallinity were degraded faster at the early stage of seedling growth but had high resistance to in situ degradation during TRS seedling growth.

CONCLUSIONS: The B-type crystallinity and long branch-chains of amylopectin in TRS seed had high resistance to in situ degradation, which inhibited TRS seedling growth.}, } @article {pmid29310583, year = {2018}, author = {Peng, M and Li, S and He, Q and Zhao, J and Li, L and Ma, H}, title = {Proteomics reveals changes in hepatic proteins during chicken embryonic development: an alternative model to study human obesity.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {29}, pmid = {29310583}, issn = {1471-2164}, support = {31572483//the National Natural Science Foundation of China/International ; }, mesh = {Animals ; Chick Embryo ; Chromatography, Liquid ; Computational Biology/methods ; Disease Models, Animal ; *Embryonic Development/genetics ; Humans ; Liver/*embryology/*metabolism ; Obesity/etiology/metabolism ; Protein Interaction Mapping ; Protein Interaction Maps ; *Proteome ; *Proteomics/methods ; Signal Transduction ; Spectrometry, Mass, Electrospray Ionization ; Tandem Mass Spectrometry ; }, abstract = {BACKGROUND: Chicken embryos are widely used as a model for studies of obesity; however, no detailed information is available about the dynamic changes of proteins during the regulation of adipose biology and metabolism. Thus, the present study used an isobaric tags for relative and absolute quantitation (iTRAQ)-based proteomic approach to identify the changes in protein abundance at different stages of chicken embryonic development.

RESULTS: In this study, the abundances of 293 hepatic proteins in 19-day old of chicken embryos compared with 14-day old and 160 hepatic proteins at hatching compared with 19-day old embryos were significantly changed. Pathway analysis showed that fatty acid degradation (upregulated ACAA2, CPT1A, and ACOX1), protein folding (upregulated PDIs, CALR3, LMAN1, and UBQLN1) and gluconeogenesis (upregulated ACSS1, AKR1A1, ALDH3A2, ALDH7A1, and FBP2) were enhanced from embryonic day 14 (E14) to E19 of chicken embryo development. Analysis of the differentially abundant proteins indicated that glycolysis was not the main way to produce energy from E19 to hatching day during chicken embryo development. In addition, purine metabolism was enhanced, as deduced from increased IMPDH2, NT5C, PGM2, and XDH abundances, and the decrease of growth rate could be overcome by increasing the abundance of ribosomal proteins from E19 to the hatching day.

CONCLUSION: The levels of certain proteins were coordinated with each other to regulate the changes in metabolic pathways to satisfy the requirement for growth and development at different stages of chicken embryo development. Importantly, ACAA2, CPT1A, and ACOX1 might be key factors to control fat deposition during chicken embryonic development. These results provided information showing that chicken is a useful model to further investigate the mechanism of obesity and insulin resistance in humans.}, } @article {pmid29310579, year = {2018}, author = {Arboleya, S and Bottacini, F and O'Connell-Motherway, M and Ryan, CA and Ross, RP and van Sinderen, D and Stanton, C}, title = {Gene-trait matching across the Bifidobacterium longum pan-genome reveals considerable diversity in carbohydrate catabolism among human infant strains.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {33}, pmid = {29310579}, issn = {1471-2164}, support = {SFI/12/RC/2273//Science Foundation Ireland/Ireland ; 10FDairy//Department of Agriculture, Food and the Marine/International ; }, mesh = {Bifidobacterium longum/*genetics/*metabolism ; Biodiversity ; *Carbohydrate Metabolism ; Databases, Genetic ; Gastrointestinal Microbiome ; *Genes, Bacterial ; *Genome, Bacterial ; Humans ; Infant ; Infant, Newborn ; Phylogeny ; Probiotics ; Quantitative Trait Loci ; *Quantitative Trait, Heritable ; }, abstract = {BACKGROUND: Bifidobacterium longum is a common member of the human gut microbiota and is frequently present at high numbers in the gut microbiota of humans throughout life, thus indicative of a close symbiotic host-microbe relationship. Different mechanisms may be responsible for the high competitiveness of this taxon in its human host to allow stable establishment in the complex and dynamic intestinal microbiota environment. The objective of this study was to assess the genetic and metabolic diversity in a set of 20 B. longum strains, most of which had previously been isolated from infants, by performing whole genome sequencing and comparative analysis, and to analyse their carbohydrate utilization abilities using a gene-trait matching approach.

RESULTS: We analysed their pan-genome and their phylogenetic relatedness. All strains clustered in the B. longum ssp. longum phylogenetic subgroup, except for one individual strain which was found to cluster in the B. longum ssp. suis phylogenetic group. The examined strains exhibit genomic diversity, while they also varied in their sugar utilization profiles. This allowed us to perform a gene-trait matching exercise enabling the identification of five gene clusters involved in the utilization of xylo-oligosaccharides, arabinan, arabinoxylan, galactan and fucosyllactose, the latter of which is an abundant human milk oligosaccharide (HMO).

CONCLUSIONS: The results showed high diversity in terms of genes and predicted glycosyl-hydrolases, as well as the ability to metabolize a large range of sugars. Moreover, we corroborate the capability of B. longum ssp. longum to metabolise HMOs. Ultimately, their intraspecific genomic diversity and the ability to consume a wide assortment of carbohydrates, ranging from plant-derived carbohydrates to HMOs, may provide an explanation for the competitive advantage and persistence of B. longum in the human gut microbiome.}, } @article {pmid29310578, year = {2018}, author = {Zaidan, H and Ramaswami, G and Golumbic, YN and Sher, N and Malik, A and Barak, M and Galiani, D and Dekel, N and Li, JB and Gaisler-Salomon, I}, title = {A-to-I RNA editing in the rat brain is age-dependent, region-specific and sensitive to environmental stress across generations.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {28}, pmid = {29310578}, issn = {1471-2164}, support = {R01GM102484/NH/NIH HHS/United States ; 484/10//Israel Science Foundation/International ; T32 HG000044/HG/NHGRI NIH HHS/United States ; R01 GM102484/GM/NIGMS NIH HHS/United States ; 2015036//United States - Israel Binational Agricultural Research and Development Fund/International ; T-2014227//United States - Israel Binational Science Foundation/International ; }, mesh = {Adenosine/*metabolism ; Adenosine Deaminase/genetics/metabolism ; Age Factors ; Animals ; Brain/*metabolism ; *Environment ; Epigenesis, Genetic ; Female ; Gene Expression Profiling ; Gene Expression Regulation ; *Gene-Environment Interaction ; Inosine/*metabolism ; Organ Specificity/genetics ; RNA/*genetics/*metabolism ; *RNA Editing ; Rats ; Receptor, Serotonin, 5-HT2C/genetics/metabolism ; Stress, Physiological/*genetics ; }, abstract = {BACKGROUND: Adenosine-to-inosine (A-to-I) RNA editing is an epigenetic modification catalyzed by adenosine deaminases acting on RNA (ADARs), and is especially prevalent in the brain. We used the highly accurate microfluidics-based multiplex PCR sequencing (mmPCR-seq) technique to assess the effects of development and environmental stress on A-to-I editing at 146 pre-selected, conserved sites in the rat prefrontal cortex and amygdala. Furthermore, we asked whether changes in editing can be observed in offspring of stress-exposed rats. In parallel, we assessed changes in ADARs expression levels.

RESULTS: In agreement with previous studies, we found editing to be generally higher in adult compared to neonatal rat brain. At birth, editing was generally lower in prefrontal cortex than in amygdala. Stress affected editing at the serotonin receptor 2c (Htr2c), and editing at this site was significantly altered in offspring of rats exposed to prereproductive stress across two generations. Stress-induced changes in Htr2c editing measured with mmPCR-seq were comparable to changes measured with Sanger and Illumina sequencing. Developmental and stress-induced changes in Adar and Adarb1 mRNA expression were observed but did not correlate with editing changes.

CONCLUSIONS: Our findings indicate that mmPCR-seq can accurately detect A-to-I RNA editing in rat brain samples, and confirm previous accounts of a developmental increase in RNA editing rates. Our findings also point to stress in adolescence as an environmental factor that alters RNA editing patterns several generations forward, joining a growing body of literature describing the transgenerational effects of stress.}, } @article {pmid29310570, year = {2018}, author = {Wang, M and Abrams, ZB and Kornblau, SM and Coombes, KR}, title = {Thresher: determining the number of clusters while removing outliers.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {9}, pmid = {29310570}, issn = {1471-2105}, support = {P50 CA168505/CA/NCI NIH HHS/United States ; P50 CA070907//NIH/NCI/International ; P30 CA016058//NIH/NCI/International ; P50 CA168505//NIH/NCI/International ; P30 CA016058/CA/NCI NIH HHS/United States ; P50 CA070907/CA/NCI NIH HHS/United States ; DMS-1440386//National Science Foundation/International ; R01 CA182905/CA/NCI NIH HHS/United States ; T15 LM011270/LM/NLM NIH HHS/United States ; R01 CA182905//NIH/NCI/International ; }, mesh = {Algorithms ; Breast Neoplasms/metabolism/pathology ; *Cluster Analysis ; Female ; Humans ; Monte Carlo Method ; Principal Component Analysis ; }, abstract = {BACKGROUND: Cluster analysis is the most common unsupervised method for finding hidden groups in data. Clustering presents two main challenges: (1) finding the optimal number of clusters, and (2) removing "outliers" among the objects being clustered. Few clustering algorithms currently deal directly with the outlier problem. Furthermore, existing methods for identifying the number of clusters still have some drawbacks. Thus, there is a need for a better algorithm to tackle both challenges.

RESULTS: We present a new approach, implemented in an R package called Thresher, to cluster objects in general datasets. Thresher combines ideas from principal component analysis, outlier filtering, and von Mises-Fisher mixture models in order to select the optimal number of clusters. We performed a large Monte Carlo simulation study to compare Thresher with other methods for detecting outliers and determining the number of clusters. We found that Thresher had good sensitivity and specificity for detecting and removing outliers. We also found that Thresher is the best method for estimating the optimal number of clusters when the number of objects being clustered is smaller than the number of variables used for clustering. Finally, we applied Thresher and eleven other methods to 25 sets of breast cancer data downloaded from the Gene Expression Omnibus; only Thresher consistently estimated the number of clusters to lie in the range of 4-7 that is consistent with the literature.

CONCLUSIONS: Thresher is effective at automatically detecting and removing outliers. By thus cleaning the data, it produces better estimates of the optimal number of clusters when there are more variables than objects. When we applied Thresher to a variety of breast cancer datasets, it produced estimates that were both self-consistent and consistent with the literature. We expect Thresher to be useful for studying a wide variety of biological datasets.}, } @article {pmid29310567, year = {2018}, author = {Zheng, Y and Janke, A}, title = {Gene flow analysis method, the D-statistic, is robust in a wide parameter space.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {10}, pmid = {29310567}, issn = {1471-2105}, mesh = {Animals ; *Gene Flow ; Genomics/*methods ; Models, Genetic ; Population Density ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: We evaluated the sensitivity of the D-statistic, a parsimony-like method widely used to detect gene flow between closely related species. This method has been applied to a variety of taxa with a wide range of divergence times. However, its parameter space and thus its applicability to a wide taxonomic range has not been systematically studied. Divergence time, population size, time of gene flow, distance of outgroup and number of loci were examined in a sensitivity analysis.

RESULT: The sensitivity study shows that the primary determinant of the D-statistic is the relative population size, i.e. the population size scaled by the number of generations since divergence. This is consistent with the fact that the main confounding factor in gene flow detection is incomplete lineage sorting by diluting the signal. The sensitivity of the D-statistic is also affected by the direction of gene flow, size and number of loci. In addition, we examined the ability of the f-statistics, [Formula: see text] and [Formula: see text], to estimate the fraction of a genome affected by gene flow; while these statistics are difficult to implement to practical questions in biology due to lack of knowledge of when the gene flow happened, they can be used to compare datasets with identical or similar demographic background.

CONCLUSIONS: The D-statistic, as a method to detect gene flow, is robust against a wide range of genetic distances (divergence times) but it is sensitive to population size. The D-statistic should only be applied with critical reservation to taxa where population sizes are large relative to branch lengths in generations.}, } @article {pmid29310123, year = {2018}, author = {Giammichele, N and Charpinet, S and Fontaine, G and Brassard, P and Green, EM and Van Grootel, V and Bergeron, P and Zong, W and Dupret, MA}, title = {A large oxygen-dominated core from the seismic cartography of a pulsating white dwarf.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {73-76}, doi = {10.1038/nature25136}, pmid = {29310123}, issn = {1476-4687}, abstract = {White-dwarf stars are the end product of stellar evolution for most stars in the Universe. Their interiors bear the imprint of fundamental mechanisms that occur during stellar evolution. Moreover, they are important chronometers for dating galactic stellar populations, and their mergers with other white dwarfs now appear to be responsible for producing the type Ia supernovae that are used as standard cosmological candles. However, the internal structure of white-dwarf stars-in particular their oxygen content and the stratification of their cores-is still poorly known, because of remaining uncertainties in the physics involved in stellar modelling codes. Here we report a measurement of the radial chemical stratification (of oxygen, carbon and helium) in the hydrogen-deficient white-dwarf star KIC08626021 (J192904.6+444708), independently of stellar-evolution calculations. We use archival data coupled with asteroseismic sounding techniques to determine the internal constitution of this star. We find that the oxygen content and extent of its core exceed the predictions of existing models of stellar evolution. The central homogeneous core has a mass of 0.45 solar masses, and is composed of about 86 per cent oxygen by mass. These values are respectively 40 per cent and 15 per cent greater than those expected from typical white-dwarf models. These findings challenge present theories of stellar evolution and their constitutive physics, and open up an avenue for calibrating white-dwarf cosmochronology.}, } @article {pmid29310122, year = {2018}, author = {Collins, J and Robinson, C and Danhof, H and Knetsch, CW and van Leeuwen, HC and Lawley, TD and Auchtung, JM and Britton, RA}, title = {Dietary trehalose enhances virulence of epidemic Clostridium difficile.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {291-294}, pmid = {29310122}, issn = {1476-4687}, support = {P30 DK056338/DK/NIDDK NIH HHS/United States ; R01 AI123278/AI/NIAID NIH HHS/United States ; U01 AI124290/AI/NIAID NIH HHS/United States ; 5U19AI09087202/NH/NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Clostridium Infections/*epidemiology/*microbiology ; Clostridium difficile/*drug effects/genetics/metabolism/*pathogenicity ; Dietary Sugars/administration & dosage/metabolism/*pharmacology ; Female ; Gastrointestinal Microbiome ; Humans ; Male ; Mice ; Mice, Inbred C57BL ; Multigene Family ; Phosphoenolpyruvate Sugar Phosphotransferase System/genetics/metabolism ; Point Mutation ; Repressor Proteins/genetics/metabolism ; Ribotyping ; Trehalose/administration & dosage/metabolism/*pharmacology ; Virulence/*drug effects ; }, abstract = {Clostridium difficile disease has recently increased to become a dominant nosocomial pathogen in North America and Europe, although little is known about what has driven this emergence. Here we show that two epidemic ribotypes (RT027 and RT078) have acquired unique mechanisms to metabolize low concentrations of the disaccharide trehalose. RT027 strains contain a single point mutation in the trehalose repressor that increases the sensitivity of this ribotype to trehalose by more than 500-fold. Furthermore, dietary trehalose increases the virulence of a RT027 strain in a mouse model of infection. RT078 strains acquired a cluster of four genes involved in trehalose metabolism, including a PTS permease that is both necessary and sufficient for growth on low concentrations of trehalose. We propose that the implementation of trehalose as a food additive into the human diet, shortly before the emergence of these two epidemic lineages, helped select for their emergence and contributed to hypervirulence.}, } @article {pmid29310121, year = {2018}, author = {Stolper, DA and Keller, CB}, title = {A record of deep-ocean dissolved O2 from the oxidation state of iron in submarine basalts.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {323-327}, doi = {10.1038/nature25009}, pmid = {29310121}, issn = {1476-4687}, mesh = {Animals ; Geologic Sediments/*chemistry ; History, Ancient ; Iron/*chemistry ; Oceans and Seas ; Oxidation-Reduction ; Oxygen/*analysis ; Seawater/*chemistry ; Silicates/*chemistry ; }, abstract = {The oxygenation of the deep ocean in the geological past has been associated with a rise in the partial pressure of atmospheric molecular oxygen (O2) to near-present levels and the emergence of modern marine biogeochemical cycles. It has also been linked to the origination and diversification of early animals. It is generally thought that the deep ocean was largely anoxic from about 2,500 to 800 million years ago, with estimates of the occurrence of deep-ocean oxygenation and the linked increase in the partial pressure of atmospheric oxygen to levels sufficient for this oxygenation ranging from about 800 to 400 million years ago. Deep-ocean dissolved oxygen concentrations over this interval are typically estimated using geochemical signatures preserved in ancient continental shelf or slope sediments, which only indirectly reflect the geochemical state of the deep ocean. Here we present a record that more directly reflects deep-ocean oxygen concentrations, based on the ratio of Fe3+ to total Fe in hydrothermally altered basalts formed in ocean basins. Our data allow for quantitative estimates of deep-ocean dissolved oxygen concentrations from 3.5 billion years ago to 14 million years ago and suggest that deep-ocean oxygenation occurred in the Phanerozoic (541 million years ago to the present) and potentially not until the late Palaeozoic (less than 420 million years ago).}, } @article {pmid29310120, year = {2018}, author = {Yordanova, MM and Loughran, G and Zhdanov, AV and Mariotti, M and Kiniry, SJ and O'Connor, PBF and Andreev, DE and Tzani, I and Saffert, P and Michel, AM and Gladyshev, VN and Papkovsky, DB and Atkins, JF and Baranov, PV}, title = {AMD1 mRNA employs ribosome stalling as a mechanism for molecular memory formation.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {356-360}, doi = {10.1038/nature25174}, pmid = {29310120}, issn = {1476-4687}, support = {CA080946/NH/NIH HHS/United States ; GM065204/NH/NIH HHS/United States ; }, mesh = {Adenosylmethionine Decarboxylase/*genetics ; Codon, Terminator/*genetics ; HEK293 Cells ; Humans ; Lysosomes/metabolism ; *Models, Genetic ; Open Reading Frames/genetics ; Phylogeny ; Proteasome Endopeptidase Complex/metabolism ; *Protein Biosynthesis ; RNA, Messenger/*genetics ; Ribosomes/*metabolism ; Stochastic Processes ; Templates, Genetic ; }, abstract = {In addition to acting as template for protein synthesis, messenger RNA (mRNA) often contains sensory sequence elements that regulate this process. Here we report a new mechanism that limits the number of complete protein molecules that can be synthesized from a single mRNA molecule of the human AMD1 gene encoding adenosylmethionine decarboxylase 1 (AdoMetDC). A small proportion of ribosomes translating AMD1 mRNA stochastically read through the stop codon of the main coding region. These readthrough ribosomes then stall close to the next in-frame stop codon, eventually forming a ribosome queue, the length of which is proportional to the number of AdoMetDC molecules that were synthesized from the same AMD1 mRNA. Once the entire spacer region between the two stop codons is filled with queueing ribosomes, the queue impinges upon the main AMD1 coding region halting its translation. Phylogenetic analysis suggests that this mechanism is highly conserved in vertebrates and existed in their common ancestor. We propose that this mechanism is used to count and limit the number of protein molecules that can be synthesized from a single mRNA template. It could serve to safeguard from dysregulated translation that may occur owing to errors in transcription or mRNA damage.}, } @article {pmid29309997, year = {2018}, author = {Bonilla-Rosso, G and Engel, P}, title = {Functional roles and metabolic niches in the honey bee gut microbiota.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {69-76}, doi = {10.1016/j.mib.2017.12.009}, pmid = {29309997}, issn = {1879-0364}, mesh = {Animals ; Bacteria/genetics/*metabolism ; Bees/*microbiology ; Body Weight ; Fermentation ; Gastrointestinal Microbiome/genetics/*physiology ; Gastrointestinal Tract/microbiology/physiology ; Genomics/methods ; Germ-Free Life ; Pollen/metabolism ; }, abstract = {Gut microbiota studies on diverse animals facilitate our understanding of the general principles governing microbiota-host interactions. The honey bee adds a relevant study system due to the simplicity and experimental tractability of its gut microbiota, but also because bees are important pollinators that suffer from population declines worldwide. The use of gnotobiotic bees combined with genetic tools, 'omics' analysis, and experimental microbiology has recently provided important insights about the impact of the microbiota on bee health and the general functioning of gut ecosystems.}, } @article {pmid29309848, year = {2018}, author = {Li, YC and Zhong, DL and Rao, GY and Wen, J and Ren, Y and Zhang, JQ}, title = {Gone with the trees: Phylogeography of Rhodiola sect. Trifida (Crassulaceae) reveals multiple refugia on the Qinghai-Tibetan Plateau.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {110-120}, doi = {10.1016/j.ympev.2018.01.001}, pmid = {29309848}, issn = {1095-9513}, mesh = {Base Sequence ; Cell Nucleus/genetics ; DNA, Chloroplast/genetics ; Ecosystem ; Genetic Variation ; Genetics, Population ; Haplotypes/genetics ; Phylogeny ; *Phylogeography ; *Refugium ; Rhodiola/*genetics ; Ribotyping ; Tibet ; Trees/*genetics ; }, abstract = {Quaternary climatic oscillations have had tremendous effects on current distribution of species. Previous studies unraveled multiple microrefugia on the Qinghai-Tibetan Plateau (QTP) in two woody plants. Still we know little whether herbs growing in forests responded to climatic oscillations similarly. We herein conducted a phylogeographic study on Rhodiola sect. Trifida, an herbaceous group endemic to the QTP, which mainly growing on the forest floors, using plastid and ITS sequences as well as ecological niche modeling. The origin and divergence of major clades of sect. Trifida were in accordance with the last phase of the QTP uplifts. Mismatch distribution analysis indicated a range expansion dated to ca. 135 thousand years ago. A high frequency and an even distribution of private haplotypes in both plastid and ITS data sets throughout the distribution of sect. Trifida were detected. The ecological niche modeling results showed that there were suitable habitats on the QTP platform during the LGM. Our results found that multiple microrefugia existed on the QTP platform, supporting the hypothesis that species with similar geographic distribution and inhabiting the same community had similar responses to the Quaternary climatic oscillations. Furthermore, species delimitations in sect. Trifida need to be tested based on integrative evidence from morphological, ecological and genetic data.}, } @article {pmid29309689, year = {2018}, author = {Kumar, S and Rowe, H}, title = {MBE Citation Classics (2018 Edition).}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {1-2}, doi = {10.1093/molbev/msx313}, pmid = {29309689}, issn = {1537-1719}, } @article {pmid29309688, year = {2018}, author = {Hardy, CM and Burke, MK and Everett, LJ and Han, MV and Lantz, KM and Gibbs, AG}, title = {Genome-Wide Analysis of Starvation-Selected Drosophila melanogaster-A Genetic Model of Obesity.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {50-65}, pmid = {29309688}, issn = {1537-1719}, abstract = {Experimental evolution affords the opportunity to investigate adaptation to stressful environments. Studies combining experimental evolution with whole-genome resequencing have provided insight into the dynamics of adaptation and a new tool to uncover genes associated with polygenic traits. Here, we selected for starvation resistance in populations of Drosophila melanogaster for over 80 generations. In response, the starvation-selected lines developed an obese condition, storing nearly twice the level of total lipids than their unselected controls. Although these fats provide a ∼3-fold increase in starvation resistance, the imbalance in lipid homeostasis incurs evolutionary cost. Some of these tradeoffs resemble obesity-associated pathologies in mammals including metabolic depression, low activity levels, dilated cardiomyopathy, and disrupted sleeping patterns. To determine the genetic basis of these traits, we resequenced genomic DNA from the selected lines and their controls. We found 1,046,373 polymorphic sites, many of which diverged between selection treatments. In addition, we found a wide range of genetic heterogeneity between the replicates of the selected lines, suggesting multiple mechanisms of adaptation. Genome-wide heterozygosity was low in the selected populations, with many large blocks of SNPs nearing fixation. We found candidate loci under selection by using an algorithm to control for the effects of genetic drift. These loci were mapped to a set of 382 genes, which associated with many processes including nutrient response, catabolic metabolism, and lipid droplet function. The results of our study speak to the evolutionary origins of obesity and provide new targets to understand the polygenic nature of obesity in a unique model system.}, } @article {pmid29309580, year = {2018}, author = {Topp, E and Larsson, DGJ and Miller, DN and Van den Eede, C and Virta, MPJ}, title = {Antimicrobial resistance and the environment: assessment of advances, gaps and recommendations for agriculture, aquaculture and pharmaceutical manufacturing.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fix185}, pmid = {29309580}, issn = {1574-6941}, abstract = {A roundtable discussion held at the fourth International Symposium on the Environmental Dimension of Antibiotic Resistance (EDAR4) considered key issues concerning the impact on the environment of antibiotic use in agriculture and aquaculture, and emissions from antibiotic manufacturing. The critical control points for reducing emissions of antibiotics from agriculture are antibiotic stewardship and the pre-treatment of manure and sludge to abate antibiotic-resistant bacteria. Antibiotics are sometimes added to fish and shellfish production sites via the feed, representing a direct route of contamination of the aquatic environment. Vaccination reduces the need for antibiotic use in high value (e.g. salmon) production systems. Consumer and regulatory pressure will over time contribute to reducing the emission of very high concentrations of antibiotics from manufacturing. Research priorities include the development of technologies, practices and incentives that will allow effective reduction in antibiotic use, together with evidence-based standards for antibiotic residues in effluents. All relevant stakeholders need to be aware of the threat of antimicrobial resistance and apply best practice in agriculture, aquaculture and pharmaceutical manufacturing in order to mitigate antibiotic resistance development. Research and policy development on antimicrobial resistance mitigation must be cognizant of the varied challenges facing high and low income countries.}, } @article {pmid29307890, year = {2018}, author = {Byndloss, MX and Bäumler, AJ}, title = {The germ-organ theory of non-communicable diseases.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {103-110}, pmid = {29307890}, issn = {1740-1534}, abstract = {Gut dysbiosis is associated with many non-communicable human diseases, but the mechanisms maintaining homeostasis remain incompletely understood. Recent insights suggest that during homeostasis, epithelial hypoxia limits oxygen availability in the colon, thereby maintaining a balanced microbiota that functions as a microbial organ, producing metabolites contributing to host nutrition, immune education and niche protection. Dysbiosis is characterized by a shift in the microbial community structure from obligate to facultative anaerobes, suggesting oxygen as an important ecological driver of microbial organ dysfunction. The ensuing disruption of gut homeostasis can lead to non- communicable disease because microbiota-derived metabolites are either depleted or generated at harmful concentrations. This Opinion article describes the concept that host control over the microbial ecosystem in the colon is critical for the composition and function of our microbial organ, which provides a theoretical framework for linking microorganisms to non-communicable diseases.}, } @article {pmid29307889, year = {2018}, author = {Brown, JM and Hazen, SL}, title = {Microbial modulation of cardiovascular disease.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {3}, pages = {171-181}, pmid = {29307889}, issn = {1740-1534}, support = {R01 DK106000/DK/NIDDK NIH HHS/United States ; R01 HL103866/HL/NHLBI NIH HHS/United States ; R01 HL126827/HL/NHLBI NIH HHS/United States ; P01 HL076491/HL/NHLBI NIH HHS/United States ; R01 HL122283/HL/NHLBI NIH HHS/United States ; P50 AA024333/AA/NIAAA NIH HHS/United States ; }, abstract = {Although diet has long been known to contribute to the pathogenesis of cardiovascular disease (CVD), research over the past decade has revealed an unexpected interplay between nutrient intake, gut microbial metabolism and the host to modify the risk of developing CVD. Microbial-associated molecular patterns are sensed by host pattern recognition receptors and have been suggested to drive CVD pathogenesis. In addition, the host microbiota produces various metabolites, such as trimethylamine-N-oxide, short-chain fatty acids and secondary bile acids, that affect CVD pathogenesis. These recent advances support the notion that targeting the interactions between the host and microorganisms may hold promise for the prevention or treatment of CVD. In this Review, we summarize our current knowledge of the gut microbial mechanisms that drive CVD, with special emphasis on therapeutic interventions, and we highlight the need to establish causal links between microbial pathways and CVD pathogenesis.}, } @article {pmid29307730, year = {2018}, author = {Wolf, B and Balestra, FR and Spahr, A and Gönczy, P}, title = {ZYG-1 promotes limited centriole amplification in the C. elegans seam lineage.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {221-230}, doi = {10.1016/j.ydbio.2018.01.001}, pmid = {29307730}, issn = {1095-564X}, mesh = {Animals ; Caenorhabditis elegans/genetics/*metabolism ; Caenorhabditis elegans Proteins/genetics/*metabolism ; *Cell Division ; Centrioles/genetics/*metabolism ; *Genomic Instability ; Protein Kinases/genetics/*metabolism ; }, abstract = {Genome stability relies notably on the integrity of centrosomes and on the mitotic spindle they organize. Structural and numerical centrosome aberrations are frequently observed in human cancer, and there is increasing evidence that centrosome amplification can promote tumorigenesis. Here, we use C. elegans seam cells as a model system to analyze centrosome homeostasis in the context of a stereotyped stem like lineage. We found that overexpression of the Plk4-related kinase ZYG-1 leads to the formation of one supernumerary centriolar focus per parental centriole during the cell cycle that leads to the sole symmetric division in the seam lineage. In the following cell cycle, such supernumerary foci function as microtubule organizing centers, but do not cluster during mitosis, resulting in the formation of a multipolar spindle and then aneuploid daughter cells. Intriguingly, we found also that supernumerary centriolar foci do not assemble in the asymmetric cell divisions that precedes or that follows the symmetric seam cell division, despite the similar presence of GFP::ZYG-1. Furthermore, we established that supernumerary centrioles form earlier during development in animals depleted of the heterochronic gene lin-14, in which the symmetric division is precocious. Conversely, supernumerary centrioles are essentially not observed in animals depleted of lin-28, in which the symmetric division is lacking. These findings lead us to conclude that ZYG-1 promotes limited centriole amplification solely during the symmetric division in the C. elegans seam lineage.}, } @article {pmid29307507, year = {2018}, author = {Tavera, J and Acero P, A and Wainwright, PC}, title = {Multilocus phylogeny, divergence times, and a major role for the benthic-to-pelagic axis in the diversification of grunts (Haemulidae).}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {212-223}, doi = {10.1016/j.ympev.2017.12.032}, pmid = {29307507}, issn = {1095-9513}, mesh = {Analysis of Variance ; Animals ; *Biodiversity ; Feeding Behavior ; Fishes/anatomy & histology/*classification ; Least-Squares Analysis ; Phenotype ; *Phylogeny ; Principal Component Analysis ; Time Factors ; }, abstract = {We present a phylogenetic analysis with divergence time estimates, and an ecomorphological assessment of the role of the benthic-to-pelagic axis of diversification in the history of haemulid fishes. Phylogenetic analyses were performed on 97 grunt species based on sequence data collected from seven loci. Divergence time estimation indicates that Haemulidae originated during the mid Eocene (54.7-42.3 Ma) but that the major lineages were formed during the mid-Oligocene 30-25 Ma. We propose a new classification that reflects the phylogenetic history of grunts. Overall the pattern of morphological and functional diversification in grunts appears to be strongly linked with feeding ecology. Feeding traits and the first principal component of body shape strongly separate species that feed in benthic and pelagic habitats. The benthic-to-pelagic axis has been the major axis of ecomorphological diversification in this important group of tropical shoreline fishes, with about 13 transitions between feeding habitats that have had major consequences for head and body morphology.}, } @article {pmid29307051, year = {2018}, author = {Chen, Y and Sun, E and Song, J and Yang, L and Wu, B}, title = {Complete Genome Sequence of a Novel T7-Like Bacteriophage from a Pasteurella multocida Capsular Type A Isolate.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {574-579}, pmid = {29307051}, issn = {1432-0991}, support = {201403054//Research projects of agricultural public welfare industry of China/ ; 2014BBB010//National Science supported planning projects of Hubei Province of China/ ; }, mesh = {Animals ; Bacteriophages/classification/*genetics/isolation & purification ; Base Composition ; China ; *Genome, Viral ; Open Reading Frames ; Pasteurella multocida/*virology ; Podoviridae/classification/*genetics/isolation & purification ; Sequence Analysis, DNA ; Sewage/virology ; Swine ; Viral Proteins/genetics ; }, abstract = {A novel virulent bacteriophage, vB_PmuP_PHB02 (phage PHB02), infecting Pasteurella multocida capsular type A strains, was isolated from wastewater from a swine farm in China. Phage PHB02 has a linear double-stranded DNA genome consisting of 38,670 base pairs (bp), with a G+C content of 40.8% and a 127-bp terminal redundancy. Forty-eight putative open reading frames were identified, and no transfer RNA-encoding genes were detected. The morphology and genomic structure of phage PHB02 resemble those of T7-like phages belonging to the family Podoviridae, of the order Caudovirales. Phage PHB02 was stable over a wide range of temperatures (4-50 °C) and pH values (5.0-9.0), and lysed 30 of the 31 capsular-type-A P. multocida strains tested. Phage PHB02 had no effect on other bacterial species or on P. multocida strains belonging to capsular types D or F.}, } @article {pmid29306861, year = {2018}, author = {Entcheva, E}, title = {Uncovering an electrically heterogeneous cardiomyocyte by FRAP-quantified diffusion in the T-tubules.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E560-E561}, pmid = {29306861}, issn = {1091-6490}, mesh = {Diffusion ; *Fluorescence Recovery After Photobleaching ; *Myocytes, Cardiac ; Sarcolemma ; }, } @article {pmid29306562, year = {2018}, author = {Grabenstein, KC and Taylor, SA}, title = {Breaking Barriers: Causes, Consequences, and Experimental Utility of Human-Mediated Hybridization.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {198-212}, doi = {10.1016/j.tree.2017.12.008}, pmid = {29306562}, issn = {1872-8383}, mesh = {Animals ; *Biodiversity ; *Conservation of Natural Resources ; Ecosystem ; Humans ; *Hybridization, Genetic ; Plants ; }, abstract = {Hybridization between naturally co-occurring species that normally do not interbreed is being documented following anthropogenic habitat modifications for an increasing number of taxa. Here, we evaluate the mechanisms by which disturbance promotes hybridization and highlight the utility of human-caused hybridization for understanding evolution. Monitoring hybridization dynamics before, and following, disturbance over multiple timescales offers a unique opportunity to understand how disturbances alter species interactions and to pinpoint the mechanisms that cause species barriers to fail. Identifying the conditions promoting hybridization in disturbed habitats, the generality of these conditions across taxa, and the taxa most affected by human-mediated change is critical for furthering our understanding of human impacts on evolution and for informing management.}, } @article {pmid29306554, year = {2018}, author = {Pratama, AA and van Elsas, JD}, title = {The 'Neglected' Soil Virome - Potential Role and Impact.}, journal = {Trends in microbiology}, volume = {26}, number = {8}, pages = {649-662}, doi = {10.1016/j.tim.2017.12.004}, pmid = {29306554}, issn = {1878-4380}, abstract = {Bacteriophages are among the most abundant and diverse biological units in the biosphere. They have contributed to our understanding of the central dogma of biology and have been instrumental in the evolutionary success of bacterial pathogens. In contrast to our current understanding of marine viral communities, the soil virome and its function in terrestrial ecosystems has remained relatively understudied. Here, we examine, in a comparative fashion, the knowledge gathered from studies performed in soil versus marine settings. We address the information with respect to the abundance, diversity, ecological significance, and effects of, in particular, bacteriophages on their host's evolutionary trajectories. We also identify the main challenges that soil virology faces and the studies that are required to accompany the current developments in marine settings.}, } @article {pmid29306330, year = {2018}, author = {Liu, J and Sharma, A and Niewiara, MJ and Singh, R and Ming, R and Yu, Q}, title = {Papain-like cysteine proteases in Carica papaya: lineage-specific gene duplication and expansion.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {26}, pmid = {29306330}, issn = {1471-2164}, support = {2015N20002-1//Department of Science and Technology of Fujian Province/International ; 31628013//National Natural Science Foundation of China/International ; TEX0-1-9374//National Institute of Food and Agriculture/International ; 201608350085//China Scholarship Council/International ; }, mesh = {Carica/*enzymology/genetics ; *Cell Lineage ; *Gene Duplication ; Genome, Plant ; High-Throughput Nucleotide Sequencing/methods ; Multigene Family ; Papain/classification/*genetics ; Phylogeny ; Plant Proteins/*genetics ; }, abstract = {BACKGROUND: Papain-like cysteine proteases (PLCPs), a large group of cysteine proteases structurally related to papain, play important roles in plant development, senescence, and defense responses. Papain, the first cysteine protease whose structure was determined by X-ray crystallography, plays a crucial role in protecting papaya from herbivorous insects. Except the four major PLCPs purified and characterized in papaya latex, the rest of the PLCPs in papaya genome are largely unknown.

RESULTS: We identified 33 PLCP genes in papaya genome. Phylogenetic analysis clearly separated plant PLCP genes into nine subfamilies. PLCP genes are not equally distributed among the nine subfamilies and the number of PLCPs in each subfamily does not increase or decrease proportionally among the seven selected plant species. Papaya showed clear lineage-specific gene expansion in the subfamily III. Interestingly, all four major PLCPs purified from papaya latex, including papain, chymopapain, glycyl endopeptidase and caricain, were grouped into the lineage-specific expansion branch in the subfamily III. Mapping PLCP genes on chromosomes of five plant species revealed that lineage-specific expansions of PLCP genes were mostly derived from tandem duplications. We estimated divergence time of papaya PLCP genes of subfamily III. The major duplication events leading to lineage-specific expansion of papaya PLCP genes in subfamily III were estimated at 48 MYA, 34 MYA, and 16 MYA. The gene expression patterns of the papaya PLCP genes in different tissues were assessed by transcriptome sequencing and qRT-PCR. Most of the papaya PLCP genes of subfamily III expressed at high levels in leaf and green fruit tissues.

CONCLUSIONS: Tandem duplications played the dominant role in affecting copy number of PLCPs in plants. Significant variations in size of the PLCP subfamilies among species may reflect genetic adaptation of plant species to different environments. The lineage-specific expansion of papaya PLCPs of subfamily III might have been promoted by the continuous reciprocal selective effects of herbivore attack and plant defense.}, } @article {pmid29306326, year = {2018}, author = {Ruocco, M and Baroncelli, R and Cacciola, SO and Pane, C and Monti, MM and Firrao, G and Vergara, M and Magnano di San Lio, G and Vannacci, G and Scala, F}, title = {Polyketide synthases of Diaporthe helianthi and involvement of DhPKS1 in virulence on sunflower.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {27}, pmid = {29306326}, issn = {1471-2164}, support = {B25C13000290007//Regione Campania/International ; B25B09000080007//Regione Campania/International ; }, mesh = {Agrobacterium tumefaciens/genetics/growth & development ; Ascomycota/*enzymology/genetics/isolation & purification/pathogenicity ; Gene Silencing ; Genetic Engineering ; Genome, Fungal ; Helianthus/growth & development/metabolism/*microbiology ; *Host-Pathogen Interactions ; Phylogeny ; Plant Diseases/genetics/*microbiology ; Polyketide Synthases/antagonists & inhibitors/genetics/*metabolism ; *Virulence ; }, abstract = {BACKGROUND: The early phases of Diaporthe helianthi pathogenesis on sunflower are characterized by the production of phytotoxins that may play a role in host colonisation. In previous studies, phytotoxins of a polyketidic nature were isolated and purified from culture filtrates of virulent strains of D. helianthi isolated from sunflower. A highly aggressive isolate (7/96) from France contained a gene fragment of a putative nonaketide synthase (lovB) which was conserved in a virulent D. helianthi population.

RESULTS: In order to investigate the role of polyketide synthases in D. helianthi 7/96, a draft genome of this isolate was examined. We were able to find and phylogenetically analyse 40 genes putatively coding for polyketide synthases (PKSs). Analysis of their domains revealed that most PKS genes of D. helianthi are reducing PKSs, whereas only eight lacked reducing domains. Most of the identified PKSs have orthologs shown to be virulence factors or genetic determinants for toxin production in other pathogenic fungi. One of the genes (DhPKS1) corresponded to the previously cloned D. helianthi lovB gene fragment and clustered with a nonribosomal peptide synthetase (NRPS) -PKS hybrid/lovastatin nonaketide like A. nidulans LovB. We used DhPKS1 as a case study and carried out its disruption through Agrobacterium-mediated transformation in the isolate 7/96. D. helianthi DhPKS1 deleted mutants were less virulent to sunflower compared to the wild type, indicating a role for this gene in the pathogenesis of the fungus.

CONCLUSION: The PKS sequences analysed and reported here constitute a new genomic resource that will be useful for further research on the biology, ecology and evolution of D. helianthi and generally of fungal plant pathogens.}, } @article {pmid29305558, year = {2018}, author = {Brenker, C and Schiffer, C and Wagner, IV and Tüttelmann, F and Röpke, A and Rennhack, A and Kaupp, UB and Strünker, T}, title = {Action of steroids and plant triterpenoids on CatSper Ca2+ channels in human sperm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E344-E346}, pmid = {29305558}, issn = {1091-6490}, mesh = {Calcium ; *Calcium Channels ; Humans ; Male ; Sperm Motility ; *Spermatozoa ; Steroids ; }, } @article {pmid29305557, year = {2018}, author = {Mannowetz, N and Mundt, N and Lishko, PV}, title = {Reply to Brenker et al.: The plant triterpenoid pristimerin inhibits calcium influx into human spermatozoa via CatSper.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E347-E348}, pmid = {29305557}, issn = {1091-6490}, support = {R01 GM111802/GM/NIGMS NIH HHS/United States ; R21 HD081403/HD/NICHD NIH HHS/United States ; }, mesh = {*Calcium ; Humans ; Male ; Sperm Motility/drug effects ; Spermatozoa/*drug effects ; Triterpenes ; }, } @article {pmid29305556, year = {2018}, author = {Edie, SM and Jablonski, D and Valentine, JW}, title = {Contrasting responses of functional diversity to major losses in taxonomic diversity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {732-737}, pmid = {29305556}, issn = {1091-6490}, mesh = {Animals ; *Biodiversity ; Bivalvia/classification ; Classification/*methods ; Computer Simulation ; Databases, Factual ; Extinction, Biological ; Fossils ; Genetic Speciation ; Geography ; History, Ancient ; Invertebrates ; Models, Biological ; Phylogeography/methods ; }, abstract = {Taxonomic diversity of benthic marine invertebrate shelf species declines at present by nearly an order of magnitude from the tropics to the poles in each hemisphere along the latitudinal diversity gradient (LDG), most steeply along the western Pacific where shallow-sea diversity is at its tropical maximum. In the Bivalvia, a model system for macroevolution and macroecology, this taxonomic trend is accompanied by a decline in the number of functional groups and an increase in the evenness of taxa distributed among those groups, with maximum functional evenness (FE) in polar waters of both hemispheres. In contrast, analyses of this model system across the two era-defining events of the Phanerozoic, the Permian-Triassic and Cretaceous-Paleogene mass extinctions, show only minor declines in functional richness despite high extinction intensities, resulting in a rise in FE owing to the persistence of functional groups. We hypothesize that the spatial decline of taxonomic diversity and increase in FE along the present-day LDG primarily reflect diversity-dependent factors, whereas retention of almost all functional groups through the two mass extinctions suggests the operation of diversity-independent factors. Comparative analyses of different aspects of biodiversity thus reveal strongly contrasting biological consequences of similarly severe declines in taxonomic diversity and can help predict the consequences for functional diversity among different drivers of past, present, and future biodiversity loss.}, } @article {pmid29305555, year = {2018}, author = {Nyström, A and Bornert, O and Kühl, T and Gretzmeier, C and Thriene, K and Dengjel, J and Pfister-Wartha, A and Kiritsi, D and Bruckner-Tuderman, L}, title = {Impaired lymphoid extracellular matrix impedes antibacterial immunity in epidermolysis bullosa.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E705-E714}, pmid = {29305555}, issn = {1091-6490}, mesh = {Animals ; Collagen Type VII/*physiology ; Disease Models, Animal ; Epidermolysis Bullosa Dystrophica/*immunology ; Extracellular Matrix/immunology ; Extracellular Matrix Proteins/*metabolism ; Humans ; *Immunity, Innate ; Lymphoid Tissue/*metabolism ; Mice, Knockout ; Skin/microbiology ; }, abstract = {Genetic loss of collagen VII causes recessive dystrophic epidermolysis bullosa (RDEB), a skin fragility disorder that, unexpectedly, manifests also with elevated colonization of commensal bacteria and frequent wound infections. Here, we describe an unprecedented systemic function of collagen VII as a member of a unique innate immune-supporting multiprotein complex in spleen and lymph nodes. In this complex, collagen VII specifically binds and sequesters the innate immune activator cochlin in the lumen of lymphoid conduits. In genetic mouse models, loss of collagen VII increased bacterial colonization by diminishing levels of circulating cochlin LCCL domain. Intraperitoneal injection of collagen VII, which restored cochlin in the spleen, but not in the skin, reactivated peripheral innate immune cells via cochlin and reduced bacterial skin colonization. Systemic administration of the cochlin LCCL domain was alone sufficient to diminish bacterial supercolonization of RDEB mouse skin. Human validation demonstrated that RDEB patients displayed lower levels of systemic cochlin LCCL domain with subsequently impaired macrophage response in infected wounds. This study identifies an intrinsic innate immune dysfunction in RDEB and uncovers a unique role of the lymphoid extracellular matrix in systemic defense against bacteria.}, } @article {pmid29305385, year = {2018}, author = {Scardigli, M and Crocini, C and Ferrantini, C and Gabbrielli, T and Silvestri, L and Coppini, R and Tesi, C and Rog-Zielinska, EA and Kohl, P and Cerbai, E and Poggesi, C and Pavone, FS and Sacconi, L}, title = {Reply to Entcheva: The impact of T-tubules on action potential propagation in cardiac tissue.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E562-E563}, pmid = {29305385}, issn = {1091-6490}, support = {FS/15/3/31047//British Heart Foundation/United Kingdom ; }, mesh = {*Action Potentials ; *Heart ; Myocytes, Cardiac ; Sarcolemma ; }, } @article {pmid29305244, year = {2018}, author = {Martin, RP and Olson, EE and Girard, MG and Smith, WL and Davis, MP}, title = {Light in the darkness: New perspective on lanternfish relationships and classification using genomic and morphological data.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {71-85}, doi = {10.1016/j.ympev.2017.12.029}, pmid = {29305244}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Ecosystem ; Fishes/*anatomy & histology/*classification/genetics ; *Genomics ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Massive parallel sequencing allows scientists to gather DNA sequences composed of millions of base pairs that can be combined into large datasets and analyzed to infer organismal relationships at a genome-wide scale in non-model organisms. Although the use of these large datasets is becoming more widespread, little to no work has been done in estimating phylogenetic relationships using UCEs in deep-sea fishes. Among deep-sea animals, the 257 species of lanternfishes (Myctophiformes) are among the most important open-ocean lineages, representing half of all mesopelagic vertebrate biomass. With this relative abundance, they are key members of the midwater food web where they feed on smaller invertebrates and fishes in addition to being a primary prey item for other open-ocean animals. Understanding the evolution and relationships of midwater organisms generally, and this dominant group of fishes in particular, is necessary for understanding and preserving the underexplored deep-sea ecosystem. Despite substantial congruence in the evolutionary relationships among deep-sea lanternfishes at higher classification levels in previous studies, the relationships among tribes, genera, and species within Myctophidae often conflict across phylogenetic studies or lack resolution and support. Herein we provide the first genome-scale phylogenetic analysis of lanternfishes, and we integrate these data from across the nuclear genome with additional protein-coding gene sequences and morphological data to further test evolutionary relationships among lanternfishes. Our phylogenetic hypotheses of relationships among lanternfishes are entirely congruent across a diversity of analyses that vary in methods, taxonomic sampling, and data analyzed. Within the Myctophiformes, the Neoscopelidae is inferred to be monophyletic and sister to a monophyletic Myctophidae. The current classification of lanternfishes is incongruent with our phylogenetic tree, so we recommend revisions that retain much of the traditional tribal structure and recognize five subfamilies instead of the traditional two subfamilies. The revised monophyletic taxonomy of myctophids includes the elevation of three former lampanyctine tribes to subfamilies. A restricted Lampanyctinae was recovered sister to Notolychninae. These two clades together were recovered as the sister group to the Gymnoscopelinae. Combined, these three subfamilies were recovered as the sister group to a clade composed of a monophyletic Diaphinae sister to the traditional Myctophinae. Our results corroborate recent multilocus molecular studies that infer a polyphyletic Myctophum in Myctophinae, and a para- or polyphyletic Lampanyctus and Nannobrachium within Lampanyctinae. We resurrect Dasyscopelus and Ctenoscopelus for the independent clades traditionally classified as species of Myctophum, and we place Nannobrachium into the synonymy of Lampanyctus.}, } @article {pmid29305243, year = {2018}, author = {Kyriazis, CC and Alam, B and Wjodyla, M and Hackett, S and Hosner, P and Mays, HL and Heaney, LR and Reddy, S}, title = {Colonization and diversification of the white-browed shortwing (Aves: Muscicapidae: Brachypteryx montana) in the Philippines.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {121-131}, doi = {10.1016/j.ympev.2017.12.025}, pmid = {29305243}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Biodiversity ; Calibration ; DNA, Mitochondrial/genetics ; Genetics, Population ; Geography ; Haplotypes/genetics ; Islands ; Likelihood Functions ; Philippines ; Phylogeny ; Sequence Analysis, DNA ; Songbirds/*genetics ; Time Factors ; }, abstract = {Molecular phylogenetic approaches have greatly improved our knowledge of the pattern and process of biological diversification across the globe; however, many regions remain poorly documented, even for well-studied vertebrate taxa. The Philippine archipelago, one of the least-studied 'biodiversity hotspots', is an ideal natural laboratory for investigating the factors driving diversification in an insular and geologically dynamic setting. We investigated the history and geography of diversification of the Philippine populations of a widespread montane bird, the White-browed Shortwing (Brachypteryx montana). Leveraging dense archipelago-wide sampling, we generated a multi-locus genetic dataset (one nuclear and two mtDNA markers), which we analyzed using phylogenetic, population genetic, and coalescent-based methods. Our results demonstrate that Philippine shortwings (1) likely colonized the Philippines from the Sunda Shelf to Mindanao in the late Miocene or Pliocene, (2) diversified across inter-island barriers into three divergent lineages during the Pliocene and early Pleistocene, (3) have not diversified within the largest island, Luzon, contrary to patterns observed in other montane taxa, and (4) colonized Palawan from the oceanic Philippines rather than from Borneo, challenging the assumption of Palawan functioning exclusively as a biogeographic extension of the Sunda Shelf. Additionally, our finding that divergent (c. 4.0 mya) lineages are coexisting in secondary sympatry on Mindanao without apparent gene flow suggests that the speciation process is likely complete for these shortwing lineages. Overall, these investigations provide insight into how topography and island boundaries influence diversification within remote oceanic archipelagos and echo the results of many other studies in demonstrating that taxonomic diversity continues to be underestimated in the Philippines.}, } @article {pmid29305158, year = {2018}, author = {Massimino, L and Flores-Garcia, L and Di Stefano, B and Colasante, G and Icoresi-Mazzeo, C and Zaghi, M and Hamilton, BA and Sessa, A}, title = {TBR2 antagonizes retinoic acid dependent neuronal differentiation by repressing Zfp423 during corticogenesis.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {231-248}, doi = {10.1016/j.ydbio.2017.12.020}, pmid = {29305158}, issn = {1095-564X}, support = {R01 NS060109/NS/NINDS NIH HHS/United States ; R01 NS097534/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*drug effects/genetics ; Cell Line, Tumor ; Cerebral Cortex/cytology/*embryology ; DNA-Binding Proteins/genetics/*metabolism ; Mice ; Neural Stem Cells/cytology/*metabolism ; Organogenesis/*drug effects/genetics ; Signal Transduction/drug effects/genetics ; T-Box Domain Proteins/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; Tretinoin/*pharmacology ; }, abstract = {During cerebral cortex development, neural progenitors are required to elaborate a variety of cell differentiation signals to which they are continuously exposed. RA acid is a potent inducer of neuronal differentiation as it was found to influence cortical development. We report herein that TBR2, a transcription factor specific to Intermediate (Basal) Neural Progenitors (INPs), represses activation of the RA responsive element and expression of RA target genes in cell lines. This repressive action on RA signaling was functionally confirmed by the decrease of RA-mediated neuronal differentiation in neural stem cells stably overexpressing TBR2. In vivo mapping of RA activity in the developing cortex indicated that RA activity is detected in radial glial cells and subsequently downregulated in INPs, revealing a fine cell-type specific regulation of its signaling. Thus, TBR2 might be a molecular player in opposing RA signaling in INPs. Interestingly, this negative regulation is achieved at least in part by directly repressing the critical nuclear RA co-factor ZFP423. Indeed, we found ZFP423 to be expressed in the developing cortex and promote RA-dependent neuronal differentiation. These data indicate that TBR2 contributes to suppressing RA signaling in INPs, thereby enabling them to re-enter the cell cycle and delay neuronal differentiation.}, } @article {pmid29305089, year = {2018}, author = {Rückert, C and Ebel, GD}, title = {How Do Virus-Mosquito Interactions Lead to Viral Emergence?.}, journal = {Trends in parasitology}, volume = {34}, number = {4}, pages = {310-321}, pmid = {29305089}, issn = {1471-5007}, support = {R01 AI067380/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Arbovirus Infections/*transmission/*virology ; Arboviruses/*physiology ; Host-Pathogen Interactions/*physiology ; Humans ; Mosquito Vectors/*virology ; }, abstract = {Arboviruses such as West Nile, Zika, chikungunya, dengue, and yellow fever viruses have become highly significant global pathogens through unexpected, explosive outbreaks. While the rapid progression and frequency of recent arbovirus outbreaks is associated with long-term changes in human behavior (globalization, urbanization, climate change), there are direct mosquito-virus interactions which drive shifts in host range and alter virus transmission. This review summarizes how virus-mosquito interactions are critical for these viruses to become global pathogens at molecular, physiological, evolutionary, and epidemiological scales. Integrated proactive approaches are required in order to effectively manage the emergence of mosquito-borne arboviruses, which appears likely to continue into the indefinite future.}, } @article {pmid29304850, year = {2018}, author = {Liu, YF and Galzerani, DD and Mbadinga, SM and Zaramela, LS and Gu, JD and Mu, BZ and Zengler, K}, title = {Metabolic capability and in situ activity of microorganisms in an oil reservoir.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {5}, pmid = {29304850}, issn = {2049-2618}, support = {41530318//National Natural Science Foundation of China/International ; 41373070//National Natural Science Foundation of China/International ; 41373070//National Natural Science Foundation of China/International ; 41161160560//NSFC/RGC Joint Research Fund/International ; 201011/2014-0//CNPq under the Brazilian Scientific Mobility Program, Ciências sem Fronteiras/International ; DE-SC0012586//Biological and Environmental Research (US)/International ; }, mesh = {Acinetobacter/classification/genetics/isolation & purification ; Archaea/*classification/genetics/isolation & purification ; Archaeoglobus/classification/genetics/isolation & purification ; Bacteria/*classification/genetics/isolation & purification ; Bacterial Proteins/genetics ; China ; Gene Expression Profiling/*methods ; Metabolic Networks and Pathways ; Metagenomics/*methods ; Methanosarcinales/classification/genetics/isolation & purification ; Oil and Gas Fields/*microbiology ; Phylogeny ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Microorganisms have long been associated with oxic and anoxic degradation of hydrocarbons in oil reservoirs and oil production facilities. While we can readily determine the abundance of microorganisms in the reservoir and study their activity in the laboratory, it has been challenging to resolve what microbes are actively participating in crude oil degradation in situ and to gain insight into what metabolic pathways they deploy.

RESULTS: Here, we describe the metabolic potential and in situ activity of microbial communities obtained from the Jiangsu Oil Reservoir (China) by an integrated metagenomics and metatranscriptomics approach. Almost complete genome sequences obtained by differential binning highlight the distinct capability of different community members to degrade hydrocarbons under oxic or anoxic condition. Transcriptomic data delineate active members of the community and give insights that Acinetobacter species completely oxidize alkanes into carbon dioxide with the involvement of oxygen, and Archaeoglobus species mainly ferment alkanes to generate acetate which could be consumed by Methanosaeta species. Furthermore, nutritional requirements based on amino acid and vitamin auxotrophies suggest a complex network of interactions and dependencies among active community members that go beyond classical syntrophic exchanges; this network defines community composition and microbial ecology in oil reservoirs undergoing secondary recovery.

CONCLUSION: Our data expand current knowledge of the metabolic potential and role in hydrocarbon metabolism of individual members of thermophilic microbial communities from an oil reservoir. The study also reveals potential metabolic exchanges based on vitamin and amino acid auxotrophies indicating the presence of complex network of interactions between microbial taxa within the community.}, } @article {pmid29304830, year = {2018}, author = {Moure, UAE and Banga-Mingo, V and Gody, JC and Mwenda, JM and Fandema, J and Waku-Kouomou, D and Manengu, C and Koyazegbe, TD and Esona, MD and Bowen, MD and Gouandijka-Vasilache, I}, title = {Emergence of G12 and G9 rotavirus genotypes in the Central African Republic, January 2014 to February 2016.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {5}, pmid = {29304830}, issn = {1756-0500}, support = {001//World Health Organization/International ; }, mesh = {Central African Republic/epidemiology ; Child, Preschool ; Female ; Gastroenteritis/epidemiology/*virology ; Genotype ; Humans ; Infant ; Male ; Rotavirus/genetics/*isolation & purification ; Rotavirus Infections/epidemiology/*virology ; }, abstract = {OBJECTIVES: Rotavirus gastroenteritis is a major cause of death among children under 5 years globally. A rotavirus gastroenteritis surveillance program started in October 2011 in the Central African Republic (CAR) with the Surveillance Epidémiologique en Afrique Centrale (SURVAC) project. We present here genotyping results showing the emergence of G9 and G12 genotypes in Central African Republic.

RESULTS: Among 222 children hospitalized with acute gastroenteritis who had a stool sample collected at the sentinel site, Complexe Pédiatrique de Bangui (CPB), Bangui, Central African Republic, 100 (45%) were positive for rotavirus between January 2014 and February 2016. During this period the most common rotavirus strains were G1P[8] (37%), G12P[6] (27%) and G9P[8] (18%).}, } @article {pmid29304755, year = {2018}, author = {Callari, M and Batra, AS and Batra, RN and Sammut, SJ and Greenwood, W and Clifford, H and Hercus, C and Chin, SF and Bruna, A and Rueda, OM and Caldas, C}, title = {Computational approach to discriminate human and mouse sequences in patient-derived tumour xenografts.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {19}, pmid = {29304755}, issn = {1471-2164}, support = {260791//EUROCAN Network of Excellence/International ; 660060//H2020 Marie Skłodowska-Curie Actions/International ; //Cancer Research UK/United Kingdom ; }, mesh = {Animals ; Breast Neoplasms/genetics/metabolism ; Gene Expression Profiling ; Genomics/*methods ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Mice ; Mutation ; Sequence Alignment ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; *Xenograft Model Antitumor Assays ; }, abstract = {BACKGROUND: Patient-Derived Tumour Xenografts (PDTXs) have emerged as the pre-clinical models that best represent clinical tumour diversity and intra-tumour heterogeneity. The molecular characterization of PDTXs using High-Throughput Sequencing (HTS) is essential; however, the presence of mouse stroma is challenging for HTS data analysis. Indeed, the high homology between the two genomes results in a proportion of mouse reads being mapped as human.

RESULTS: In this study we generated Whole Exome Sequencing (WES), Reduced Representation Bisulfite Sequencing (RRBS) and RNA sequencing (RNA-seq) data from samples with known mixtures of mouse and human DNA or RNA and from a cohort of human breast cancers and their derived PDTXs. We show that using an In silico Combined human-mouse Reference Genome (ICRG) for alignment discriminates between human and mouse reads with up to 99.9% accuracy and decreases the number of false positive somatic mutations caused by misalignment by >99.9%. We also derived a model to estimate the human DNA content in independent PDTX samples. For RNA-seq and RRBS data analysis, the use of the ICRG allows dissecting computationally the transcriptome and methylome of human tumour cells and mouse stroma. In a direct comparison with previously reported approaches, our method showed similar or higher accuracy while requiring significantly less computing time.

CONCLUSIONS: The computational pipeline we describe here is a valuable tool for the molecular analysis of PDTXs as well as any other mixture of DNA or RNA species.}, } @article {pmid29304754, year = {2018}, author = {Cava, C and Bertoli, G and Colaprico, A and Olsen, C and Bontempi, G and Castiglioni, I}, title = {Integration of multiple networks and pathways identifies cancer driver genes in pan-cancer analysis.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {25}, pmid = {29304754}, issn = {1471-2164}, support = {CUP Grant B91J12000190001//INTEROMICS flagship project/International ; }, mesh = {Algorithms ; Biomarkers, Tumor/*genetics ; Case-Control Studies ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; *Gene Regulatory Networks ; Genomics/*methods ; Humans ; Neoplasms/*genetics ; *Signal Transduction ; }, abstract = {BACKGROUND: Modern high-throughput genomic technologies represent a comprehensive hallmark of molecular changes in pan-cancer studies. Although different cancer gene signatures have been revealed, the mechanism of tumourigenesis has yet to be completely understood. Pathways and networks are important tools to explain the role of genes in functional genomic studies. However, few methods consider the functional non-equal roles of genes in pathways and the complex gene-gene interactions in a network.

RESULTS: We present a novel method in pan-cancer analysis that identifies de-regulated genes with a functional role by integrating pathway and network data. A pan-cancer analysis of 7158 tumour/normal samples from 16 cancer types identified 895 genes with a central role in pathways and de-regulated in cancer. Comparing our approach with 15 current tools that identify cancer driver genes, we found that 35.6% of the 895 genes identified by our method have been found as cancer driver genes with at least 2/15 tools. Finally, we applied a machine learning algorithm on 16 independent GEO cancer datasets to validate the diagnostic role of cancer driver genes for each cancer. We obtained a list of the top-ten cancer driver genes for each cancer considered in this study.

CONCLUSIONS: Our analysis 1) confirmed that there are several known cancer driver genes in common among different types of cancer, 2) highlighted that cancer driver genes are able to regulate crucial pathways.}, } @article {pmid29304753, year = {2018}, author = {Chang, LY and Toghiani, S and Ling, A and Aggrey, SE and Rekaya, R}, title = {High density marker panels, SNPs prioritizing and accuracy of genomic selection.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {4}, pmid = {29304753}, issn = {1471-2156}, mesh = {Animals ; Breeding ; Female ; Genetics, Population ; Humans ; Male ; *Models, Genetic ; Plants/genetics ; *Polymorphism, Single Nucleotide ; Quantitative Trait, Heritable ; *Selection, Genetic ; }, abstract = {BACKGROUND: The availability of high-density (HD) marker panels, genome wide variants and sequence data creates an unprecedented opportunity to dissect the genetic basis of complex traits, enhance genomic selection (GS) and identify causal variants of disease. The disproportional increase in the number of parameters in the genetic association model compared to the number of phenotypes has led to further deterioration in statistical power and an increase in co-linearity and false positive rates. At best, HD panels do not significantly improve GS accuracy and, at worst, reduce accuracy. This is true for both regression and variance component approaches. To remedy this situation, some form of single nucleotide polymorphisms (SNP) filtering or external information is needed. Current methods for prioritizing SNP markers (i.e. BayesB, BayesCπ) are sensitive to the increased co-linearity in HD panels which could limit their performance.

RESULTS: In this study, the usefulness of FST, a measure of allele frequency variation among populations, as an external source of information in GS was evaluated. A simulation was carried out for a trait with heritability of 0.4. Data was divided into three subpopulations based on phenotype distribution (bottom 5%, middle 90%, top 5%). Marker data were simulated to mimic a 770 K and 1.5 million SNP marker panel. A ten-chromosome genome with 200 K and 400 K SNPs was simulated. Several scenarios with varying distributions for the quantitative trait loci (QTL) effects were simulated. Using all 200 K markers and no filtering, the accuracy of genomic prediction was 0.77. When marker effects were simulated from a gamma distribution, SNPs pre-selected based on the 99.5, 99.0 and 97.5% quantile of the FST score distribution resulted in an accuracy of 0.725, 0.797, and 0.853, respectively. Similar results were observed under other simulation scenarios. Clearly, the accuracy obtained using all SNPs can be easily achieved using only 0.5 to 1% of all markers.

CONCLUSIONS: These results indicate that SNP filtering using already available external information could increase the accuracy of GS. This is especially important as next-generation sequencing technology becomes more affordable and accessible to human, animal and plant applications.}, } @article {pmid29304743, year = {2018}, author = {Zou, QL and You, XP and Li, JL and Fung, WK and Zhou, JY}, title = {A powerful parent-of-origin effects test for qualitative traits on X chromosome in general pedigrees.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {8}, pmid = {29304743}, issn = {1471-2105}, support = {R01 AR044422/AR/NIAMS NIH HHS/United States ; 81773544//National Natural Science Foundation of China/International ; R01-AR-44422/NH/NIH HHS/United States ; N01-AR-2-2263/NH/NIH HHS/United States ; R01 GM031575/GM/NIGMS NIH HHS/United States ; 2013B021800038//Science and Technology Planning Project of Guangdong Province, China/International ; 17301715//The Hong Kong Research Grants Council GRF Grant/International ; R01 GM031575/NH/NIH HHS/United States ; 81573207//National Natural Science Foundation of China/International ; 81373098//National Natural Science Foundation of China/International ; }, mesh = {Arthritis, Rheumatoid/genetics/pathology ; *Chromosomes, Human, X ; *Genomic Imprinting ; Genotype ; Humans ; Monte Carlo Method ; Pedigree ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Genomic imprinting is one of the well-known epigenetic factors causing the association between traits and genes, and has generally been examined by detecting parent-of-origin effects of alleles. A lot of methods have been proposed to test for parent-of-origin effects on autosomes based on nuclear families and general pedigrees. Although these parent-of-origin effects tests on autosomes have been available for more than 15 years, there has been no statistical test developed to test for parent-of-origin effects on X chromosome, until the parental-asymmetry test on X chromosome (XPAT) and its extensions were recently proposed. However, these methods on X chromosome are only applicable to nuclear families and thus are not suitable for general pedigrees.

RESULTS: In this article, we propose the pedigree parental-asymmetry test on X chromosome (XPPAT) statistic to test for parent-of-origin effects in the presence of association, which can accommodate general pedigrees. When there are missing genotypes in some pedigrees, we further develop the Monte Carlo pedigree parental-asymmetry test on X chromosome (XMCPPAT) to test for parent-of-origin effects, by inferring the missing genotypes given the observed genotypes based on a Monte Carlo estimation. An extensive simulation study has been carried out to investigate the type I error rates and the powers of the proposed tests. Our simulation results show that the proposed methods control the size well under the null hypothesis of no parent-of-origin effects. Moreover, XMCPPAT substantially outperforms the existing tests and has a much higher power than XPPAT which only uses complete nuclear families (with both parents) from pedigrees. We also apply the proposed methods to analyze rheumatoid arthritis data for their practical use.

CONCLUSIONS: The proposed XPPAT and XMCPPAT test statistics are valid and powerful in detecting parent-of-origin effects on X chromosome for qualitative traits based on general pedigrees and thus are recommended.}, } @article {pmid29304741, year = {2018}, author = {Rodríguez-García, MÁ and Hoehndorf, R}, title = {Inferring ontology graph structures using OWL reasoning.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {7}, pmid = {29304741}, issn = {1471-2105}, mesh = {*Algorithms ; Animals ; Area Under Curve ; Caenorhabditis elegans/genetics ; Drosophila/genetics ; Gene Ontology ; Mice ; Protein Interaction Maps/genetics ; ROC Curve ; Saccharomyces cerevisiae/genetics ; Zebrafish/genetics ; }, abstract = {BACKGROUND: Ontologies are representations of a conceptualization of a domain. Traditionally, ontologies in biology were represented as directed acyclic graphs (DAG) which represent the backbone taxonomy and additional relations between classes. These graphs are widely exploited for data analysis in the form of ontology enrichment or computation of semantic similarity. More recently, ontologies are developed in a formal language such as the Web Ontology Language (OWL) and consist of a set of axioms through which classes are defined or constrained. While the taxonomy of an ontology can be inferred directly from the axioms of an ontology as one of the standard OWL reasoning tasks, creating general graph structures from OWL ontologies that exploit the ontologies' semantic content remains a challenge.

RESULTS: We developed a method to transform ontologies into graphs using an automated reasoner while taking into account all relations between classes. Searching for (existential) patterns in the deductive closure of ontologies, we can identify relations between classes that are implied but not asserted and generate graph structures that encode for a large part of the ontologies' semantic content. We demonstrate the advantages of our method by applying it to inference of protein-protein interactions through semantic similarity over the Gene Ontology and demonstrate that performance is increased when graph structures are inferred using deductive inference according to our method. Our software and experiment results are available at http://github.com/bio-ontology-research-group/Onto2Graph .

CONCLUSIONS: Onto2Graph is a method to generate graph structures from OWL ontologies using automated reasoning. The resulting graphs can be used for improved ontology visualization and ontology-based data analysis.}, } @article {pmid29304740, year = {2018}, author = {Pfeiffer, F and Zamora-Lagos, MA and Blettinger, M and Yeroslaviz, A and Dahl, A and Gruber, S and Habermann, BH}, title = {The complete and fully assembled genome sequence of Aeromonas salmonicida subsp. pectinolytica and its comparative analysis with other Aeromonas species: investigation of the mobilome in environmental and pathogenic strains.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {20}, pmid = {29304740}, issn = {1471-2164}, mesh = {Aeromonas/genetics ; Aeromonas salmonicida/*genetics/isolation & purification/pathogenicity ; DNA Transposable Elements ; Environmental Microbiology ; Genes, Bacterial ; *Genome, Bacterial ; Genomics ; High-Throughput Nucleotide Sequencing ; *Interspersed Repetitive Sequences ; }, abstract = {BACKGROUND: Due to the predominant usage of short-read sequencing to date, most bacterial genome sequences reported in the last years remain at the draft level. This precludes certain types of analyses, such as the in-depth analysis of genome plasticity.

RESULTS: Here we report the finalized genome sequence of the environmental strain Aeromonas salmonicida subsp. pectinolytica 34mel, for which only a draft genome with 253 contigs is currently available. Successful completion of the transposon-rich genome critically depended on the PacBio long read sequencing technology. Using finalized genome sequences of A. salmonicida subsp. pectinolytica and other Aeromonads, we report the detailed analysis of the transposon composition of these bacterial species. Mobilome evolution is exemplified by a complex transposon, which has shifted from pathogenicity-related to environmental-related gene content in A. salmonicida subsp. pectinolytica 34mel.

CONCLUSION: Obtaining the complete, circular genome of A. salmonicida subsp. pectinolytica allowed us to perform an in-depth analysis of its mobilome. We demonstrate the mobilome-dependent evolution of this strain's genetic profile from pathogenic to environmental.}, } @article {pmid29304739, year = {2018}, author = {Ullah, F and Hamilton, M and Reddy, ASN and Ben-Hur, A}, title = {Exploring the relationship between intron retention and chromatin accessibility in plants.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {21}, pmid = {29304739}, issn = {1471-2164}, support = {DE-SC0010733//U.S. Department of Energy/International ; }, mesh = {Alternative Splicing ; Arabidopsis/*genetics ; Chromatin/*chemistry/metabolism ; DNA-Binding Proteins/metabolism ; Deoxyribonuclease I ; *Introns ; Oryza/*genetics ; Protein Footprinting ; }, abstract = {BACKGROUND: Intron retention (IR) is the most prevalent form of alternative splicing in plants. IR, like other forms of alternative splicing, has an important role in increasing gene product diversity and regulating transcript functionality. Splicing is known to occur co-transcriptionally and is influenced by the speed of transcription which in turn, is affected by chromatin structure. It follows that chromatin structure may have an important role in the regulation of splicing, and there is preliminary evidence in metazoans to suggest that this is indeed the case; however, nothing is known about the role of chromatin structure in regulating IR in plants. DNase I-seq is a useful experimental tool for genome-wide interrogation of chromatin accessibility, providing information on regions of chromatin with very high likelihood of cleavage by the enzyme DNase I, known as DNase I Hypersensitive Sites (DHSs). While it is well-established that promoter regions are highly accessible and are over-represented with DHSs, not much is known about DHSs in the bodies of genes, and their relationship to splicing in general, and IR in particular.

RESULTS: In this study we use publicly available DNase I-seq data in arabidopsis and rice to investigate the relationship between IR and chromatin structure. We find that IR events are highly enriched in DHSs in both species. This implies that chromatin is more open in retained introns, which is consistent with a kinetic model of the process whereby higher speeds of transcription in those regions give less time for the spliceosomal machinery to recognize and splice out those introns co-transcriptionally. The more open chromatin in IR can also be the result of regulation mediated by DNA-binding proteins. To test this, we performed an exhaustive search for footprints left by DNA-binding proteins that are associated with IR. We identified several hundred short sequence elements that exhibit footprints in their DNase I-seq coverage, the telltale sign for binding events of a regulatory protein, protecting its binding site from cleavage by DNase I. A highly significant fraction of those sequence elements are conserved between arabidopsis and rice, a strong indication of their functional importance.

CONCLUSIONS: In this study we have established an association between IR and chromatin accessibility, and presented a mechanistic hypothesis that explains the observed association from the perspective of the co-transcriptional nature of splicing. Furthermore, we identified conserved sequence elements for DNA-binding proteins that affect splicing.}, } @article {pmid29304738, year = {2018}, author = {Liu, H and Zhang, G and Wang, J and Li, J and Song, Y and Qiao, L and Niu, N and Wang, J and Ma, S and Li, L}, title = {Chemical hybridizing agent SQ-1-induced male sterility in Triticum aestivum L.: a comparative analysis of the anther proteome.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {7}, pmid = {29304738}, issn = {1471-2229}, support = {No. 2015BAD27B01//National Support Program of China/International ; No.31371697//the National Natural Science Foundation of China/International ; No.2014KTZB02-01-02//the Technological Innovation and Over Planning Projects of Shaanxi Province/International ; No.172102110165//Department of Science and Technology Planning Project of Henan Province/International ; No.15A210015//The Key Scientific Research Project in Colleges and Universities of Henan Province/International ; No.ZKNU2014111//Doctoral Scientific Research Starting Foundation of Zhoukou Normal University/International ; No.ZKNUB115103//School-based projects of Zhoukou Normal University/International ; }, mesh = {Electrophoresis, Gel, Two-Dimensional ; Flowers/*metabolism ; *Plant Breeding ; Plant Infertility/drug effects/*physiology ; Plant Proteins/*genetics/metabolism ; *Proteome ; Triticum/drug effects/*physiology ; }, abstract = {BACKGROUND: Heterosis is widely used to increase the yield of many crops. However, as wheat is a self-pollinating crop, hybrid breeding is not so successful in this organism. Even though male sterility induced by chemical hybridizing agents is an important aspect of crossbreeding, the mechanisms by which these agents induce male sterility in wheat is not well understood.

RESULTS: We performed proteomic analyses using the wheat Triticum aestivum L.to identify those proteins involved in physiological male sterility (PHYMS) induced by the chemical hybridizing agent CHA SQ-1. A total of 103 differentially expressed proteins were found by 2D-PAGE and subsequently identified by MALDI-TOF/TOF MS/MS. In general, these proteins had obvious functional tendencies implicated in carbohydrate metabolism, oxidative stress and resistance, protein metabolism, photosynthesis, and cytoskeleton and cell structure. In combination with phenotypic, tissue section, and bioinformatics analyses, the identified differentially expressed proteins revealed a complex network behind the regulation of PHYMS and pollen development. Accordingly, we constructed a protein network of male sterility in wheat, drawing relationships between the 103 differentially expressed proteins and their annotated biological pathways. To further validate our proposed protein network, we determined relevant physiological values and performed real-time PCR assays.

CONCLUSIONS: Our proteomics based approach has enabled us to identify certain tendencies in PHYMS anthers. Anomalies in carbohydrate metabolism and oxidative stress, together with premature tapetum degradation, may be the cause behind carbohydrate starvation and male sterility in CHA SQ-1 treated plants. Here, we provide important insight into the mechanisms underlying CHA SQ-1-induced male sterility. Our findings have practical implications for the application of hybrid breeding in wheat.}, } @article {pmid29304737, year = {2018}, author = {Kranz, A and Busche, T and Vogel, A and Usadel, B and Kalinowski, J and Bott, M and Polen, T}, title = {RNAseq analysis of α-proteobacterium Gluconobacter oxydans 621H.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {24}, pmid = {29304737}, issn = {1471-2164}, support = {BioSC No. 313/323-400-002 13//Ministry of Innovation, Science and Research/International ; BioSC No. 313/323-400-002 13//Ministry of Innovation, Science and Research/International ; }, mesh = {Bacterial Proteins/genetics ; *Genome, Bacterial ; Gluconobacter oxydans/*genetics/growth & development ; High-Throughput Nucleotide Sequencing/*methods ; Operon ; Promoter Regions, Genetic ; Regulatory Elements, Transcriptional ; Sequence Analysis, RNA/*methods ; Transcription Initiation Site ; *Transcriptome ; }, abstract = {BACKGROUND: The acetic acid bacterium Gluconobacter oxydans 621H is characterized by its exceptional ability to incompletely oxidize a great variety of carbohydrates in the periplasm. The metabolism of this α-proteobacterium has been characterized to some extent, yet little is known about its transcriptomes and related data. In this study, we applied two different RNAseq approaches. Primary transcriptomes enriched for 5'-ends of transcripts were sequenced to detect transcription start sites, which allow subsequent analysis of promoter motifs, ribosome binding sites, and 5´-UTRs. Whole transcriptomes were sequenced to identify expressed genes and operon structures.

RESULTS: Sequencing of primary transcriptomes of G. oxydans revealed 2449 TSSs, which were classified according to their genomic context followed by identification of promoter and ribosome binding site motifs, analysis of 5´-UTRs including validation of predicted cis-regulatory elements and correction of start codons. 1144 (41%) of all genes were found to be expressed monocistronically, whereas 1634 genes were organized in 571 operons. Together, TSSs and whole transcriptome data were also used to identify novel intergenic (18), intragenic (328), and antisense transcripts (313).

CONCLUSIONS: This study provides deep insights into the transcriptional landscapes of G. oxydans. The comprehensive transcriptome data, which we made publicly available, facilitate further analysis of promoters and other regulatory elements. This will support future approaches for rational strain development and targeted gene expression in G. oxydans. The corrections of start codons further improve the high quality genome reference and support future proteome analysis.}, } @article {pmid29304736, year = {2018}, author = {Irani, S and Trost, B and Waldner, M and Nayidu, N and Tu, J and Kusalik, AJ and Todd, CD and Wei, Y and Bonham-Smith, PC}, title = {Transcriptome analysis of response to Plasmodiophora brassicae infection in the Arabidopsis shoot and root.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {23}, pmid = {29304736}, issn = {1471-2164}, support = {20100098//Ministry of Agriculture - Saskatchewan/International ; 20100098//Saskatchewan Canola Commission/International ; }, mesh = {Arabidopsis/anatomy & histology/*genetics/metabolism/*parasitology ; Gene Expression Profiling ; *Gene Expression Regulation, Plant ; Plant Diseases/genetics/*parasitology ; Plant Growth Regulators/biosynthesis ; Plant Roots/genetics/metabolism/parasitology ; Plant Shoots/genetics/metabolism/parasitology ; *Plasmodiophorida ; Transcription Factors/genetics/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Clubroot is an important disease caused by the obligate parasite Plasmodiophora brassicae that infects the Brassicaceae. As a soil-borne pathogen, P. brassicae induces the generation of abnormal tissue in the root, resulting in the formation of galls. Root infection negatively affects the uptake of water and nutrients in host plants, severely reducing their growth and productivity. Many studies have emphasized the molecular and physiological effects of the clubroot disease on root tissues. The aim of the present study is to better understand the effect of P. brassicae on the transcriptome of both shoot and root tissues of Arabidopsis thaliana.

RESULTS: Transcriptome profiling using RNA-seq was performed on both shoot and root tissues at 17, 20 and 24 days post inoculation (dpi) of A. thaliana, a model plant host for P. brassicae. The number of differentially expressed genes (DEGs) between infected and uninfected samples was larger in shoot than in root. In both shoot and root, more genes were differentially regulated at 24 dpi than the two earlier time points. Genes that were highly regulated in response to infection in both shoot and root primarily were involved in the metabolism of cell wall compounds, lipids, and shikimate pathway metabolites. Among hormone-related pathways, several jasmonic acid biosynthesis genes were upregulated in both shoot and root tissue. Genes encoding enzymes involved in cell wall modification, biosynthesis of sucrose and starch, and several classes of transcription factors were generally differently regulated in shoot and root.

CONCLUSIONS: These results highlight the similarities and differences in the transcriptomic response of above- and below-ground tissues of the model host Arabidopsis following P. brassicae infection. The main transcriptomic changes in root metabolism during clubroot disease progression were identified. An overview of DEGs in the shoot underlined the physiological changes in above-ground tissues following pathogen establishment and disease progression. This study provides insights into host tissue-specific molecular responses to clubroot development and may have applications in the development of clubroot markers for more effective breeding strategies.}, } @article {pmid29304732, year = {2018}, author = {Gao, W and Qu, J and Zhang, J and Sonnenberg, A and Chen, Q and Zhang, Y and Huang, C}, title = {A genetic linkage map of Pleurotus tuoliensis integrated with physical mapping of the de novo sequenced genome and the mating type loci.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {18}, pmid = {29304732}, issn = {1471-2164}, support = {2014CB138305//National Basic Research Program of China/International ; CAAS, IARRP-647-46//National Nonprofit Institute Research Grant of Chinese Academy of Agricultural Sciences/International ; CARS20//China Agriculture Research System/International ; }, mesh = {*Chromosome Mapping ; *Genes, Mating Type, Fungal ; Genetic Linkage ; *Genetic Loci ; *Genome, Fungal ; Genomics ; Genotyping Techniques ; Physical Chromosome Mapping ; Pleurotus/*genetics ; }, abstract = {BACKGROUND: Pleurotus tuoliensis (Bailinggu) is a commercially cultivated mushroom species with an increasing popularity in China and other Asian countries. Commercial profits are now low, mainly due to a low yield, long cultivation period and sensitivity to diseases. Breeding efforts are thus required to improve agronomical important traits. Developing saturated genetic linkage and physical maps is a start for applying genetic and molecular approaches to accelerate the precise breeding programs.

RESULTS: Here we present a genetic linkage map for P. tuoliensis constructed by using 115 haploid monokaryons derived from a hybrid strain H6. One thousand one hundred and eighty-two SNP markers developed by 2b-RAD (type IIB restriction-site associated DNA) approach were mapped to 12 linkage groups. The map covers 1073 cM with an average marker spacing of 1.0 cM. The genome of P. tuoliensis was de novo sequenced as 40.8 Mb and consisted of 500 scaffolds (>500 bp), which showed a high level of colinearity to the genome of P. eryngii var. eryngii. A total of 97.4% SNP markers (1151) were physically localized on 78 scaffolds, and the physical length of these anchored scaffolds were 33.9 Mb representing 83.1% of the whole genome. Mating type loci A and B were mapped on separate linkage groups and identified physically on the assembled genomes. Five putative pheromone receptors and two putative pheromone precursors were identified for the mating type B locus.

CONCLUSIONS: This study reported a first genetic linkage map integrated with physical mapping of the de novo sequenced genome and the mating type loci of an important cultivated mushroom in China, P. tuoliensis. The de novo sequenced and annotated genome, assembled using a 2b-RAD generated linkage map, provides a basis for marker-assisted breeding of this economic important mushroom species.}, } @article {pmid29304730, year = {2018}, author = {Qiu, F and Ungerer, MC}, title = {Genomic abundance and transcriptional activity of diverse gypsy and copia long terminal repeat retrotransposons in three wild sunflower species.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {6}, pmid = {29304730}, issn = {1471-2229}, support = {17-217-J//Kansas Agricultural Experiment Station, Kansas State University/International ; }, mesh = {Genome Size ; *Genome, Plant ; Helianthus/*genetics/metabolism ; High-Throughput Nucleotide Sequencing ; Retroelements/*genetics ; Species Specificity ; Terminal Repeat Sequences/*genetics ; }, abstract = {BACKGROUND: Long terminal repeat (LTR) retrotransposons are highly abundant in plant genomes and require transcriptional activity for their proliferative mode of replication. These sequences exist in plant genomes as diverse sublineages within the main element superfamilies (i.e., gypsy and copia). While transcriptional activity of these elements is increasingly recognized as a regular attribute of plant transcriptomes, it is currently unknown the extent to which different sublineages of these elements are transcriptionally active both within and across species. In the current report, we utilize next generation sequencing methods to examine genomic copy number abundance of diverse LTR retrotransposon sublineages and their corresponding levels of transcriptional activity in three diploid wild sunflower species, Helianthus agrestis, H. carnosus and H. porteri.

RESULTS: The diploid sunflower species under investigation differ in genome size 2.75-fold, with 2C values of 22.93 for H. agrestis, 12.31 for H. carnosus and 8.33 for H. porteri. The same diverse gypsy and copia sublineages of LTR retrotransposons were identified across species, but with gypsy sequences consistently more abundant than copia and with global gypsy sequence abundance positively correlated with nuclear genome size. Transcriptional activity was detected for multiple copia and gypsy sequences, with significantly higher activity levels detected for copia versus gypsy. Interestingly, of 11 elements identified as transcriptionally active, 5 exhibited detectable expression in all three species and 3 exhibited detectable expression in two species.

CONCLUSIONS: Combined analyses of LTR retrotransposon genomic abundance and transcriptional activity across three sunflower species provides novel insights into genome size evolution and transposable element dynamics in this group. Despite considerable variation in nuclear genome size among species, relatively conserved patterns of LTR retrotransposon transcriptional activity were observed, with a highly overlapping set of copia and gypsy sequences observed to be transcriptionally active across species. A higher proportion of copia versus gypsy elements were found to be transcriptionally active and these sequences also were expressed at higher levels.}, } @article {pmid29304728, year = {2018}, author = {Liu, YJ and Wang, GL and Ma, J and Xu, ZS and Wang, F and Xiong, AS}, title = {Transcript profiling of sucrose synthase genes involved in sucrose metabolism among four carrot (Daucus carota L.) cultivars reveals distinct patterns.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {8}, pmid = {29304728}, issn = {1471-2229}, support = {FT201402-07//Shanxi Province Coal Based Key Scientific and Technological Project ()/International ; NCET-11-0670//New Century Excellent Talents in University ()/International ; BK20130027//Natural Science Foundation of Jiangsu Province/International ; PAPD//Priority Academic Program Development of Jiangsu Higher Education Institutions ()./International ; }, mesh = {Daucus carota/*genetics/metabolism ; Glucosyltransferases/*genetics/metabolism ; Sucrose/*metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Carrot which contains lots of nutrients has a large demand around the world. The soluble sugar content in fleshy root of carrot directly influences its taste and quality. Sucrose, as an important member of soluble sugar, is the main product of photosynthesis in higher plants and it plays pivotal roles in physiological processes including energy supply, signal transduction, transcriptional regulation, starch and cellulose synthesis, and stress tolerance. Sucrose synthase is a key enzyme involved in sucrose metabolism and is closely related to sucrose content. However, the molecular mechanism involved in sucrose metabolism in carrot has lagged behind.

RESULTS: Here, carrot roots of five developmental stages from four carrot cultivars were collected, and the contents of soluble sugar and sucrose in different stages and cultivars were surveyed. Three DcSus genes (DcSus1, DcSus2, and DcSus3), with lengths of 2427 bp, 2454 bp and 2628 bp, respectively, were identified and cloned in carrot. Phylogenetic analysis from the deduced amino acid sequences suggested that three DcSus were clustered into three distinct groups (SUSI, II and III). Results of enzymatic profiles demonstrated that the DcSus activities showed decrease trends during taproot development. Correlation analysis indicated that the DcSus activity showed negative correlation with soluble sugar content and strong negative correlation with sucrose concentration. Quantitative real-time PCR analysis showed that the expression profiles of the DcSus genes are significantly different in carrot tissues (root, leaf blade, and petiole), and the expression levels of the DcSus genes in the leaf blade were much higher than that in the root and petiole. The expression profiles of DcSus genes showed strong negative correlation with both sucrose content and soluble sugar content.

CONCLUSIONS: During carrot root development, the soluble sugar content and sucrose content showed increasing trends, while DcSus activities had persisting declinations, which may be due to the decreasing expression levels of genes encoding sucrose synthase. Our data demonstrate that synthesis of sucrose in carrot tissue is closely related with DcSus genes. The results from our study would not only provide effective insights of sucrose metabolism in carrot, but also are beneficial for biologists to improve carrot quality.}, } @article {pmid29304727, year = {2018}, author = {Malomane, DK and Reimer, C and Weigend, S and Weigend, A and Sharifi, AR and Simianer, H}, title = {Efficiency of different strategies to mitigate ascertainment bias when using SNP panels in diversity studies.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {22}, pmid = {29304727}, issn = {1471-2164}, support = {FKZ 0315528E//German Federal Ministry of Education and Research/International ; }, mesh = {Animals ; Chickens/genetics ; Gene Frequency ; *Genotyping Techniques ; Oligonucleotide Array Sequence Analysis ; *Polymorphism, Single Nucleotide ; *Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Single nucleotide polymorphism (SNP) panels have been widely used to study genomic variations within and between populations. Methods of SNP discovery have been a matter of debate for their potential of introducing ascertainment bias, and genetic diversity results obtained from the SNP genotype data can be misleading. We used a total of 42 chicken populations where both individual genotyped array data and pool whole genome resequencing (WGS) data were available. We compared allele frequency distributions and genetic diversity measures (expected heterozygosity (H e), fixation index (F ST) values, genetic distances and principal components analysis (PCA)) between the two data types. With the array data, we applied different filtering options (SNPs polymorphic in samples of two Gallus gallus wild populations, linkage disequilibrium (LD) based pruning and minor allele frequency (MAF) filtering, and combinations thereof) to assess their potential to mitigate the ascertainment bias.

RESULTS: Rare SNPs were underrepresented in the array data. Array data consistently overestimated H e compared to WGS data, however, with a similar ranking of the breeds, as demonstrated by Spearman's rank correlations ranging between 0.956 and 0.985. LD based pruning resulted in a reduced overestimation of H e compared to the other filters and slightly improved the relationship with the WGS results. The raw array data and those with polymorphic SNPs in the wild samples underestimated pairwise F ST values between breeds which had low F ST (<0.15) in the WGS, and overestimated this parameter for high WGS F ST (>0.15). LD based pruned data underestimated F ST in a consistent manner. The genetic distance matrix from LD pruned data was more closely related to that of WGS than the other array versions. PCA was rather robust in all array versions, since the population structure on the PCA plot was generally well captured in comparison to the WGS data.

CONCLUSIONS: Among the tested filtering strategies, LD based pruning was found to account for the effects of ascertainment bias in the relatively best way, producing results which are most comparable to those obtained from WGS data and therefore is recommended for practical use.}, } @article {pmid29304726, year = {2018}, author = {Zhu, Q and Fisher, SA and Dueck, H and Middleton, S and Khaladkar, M and Kim, J}, title = {PIVOT: platform for interactive analysis and visualization of transcriptomics data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {6}, pmid = {29304726}, issn = {1471-2105}, support = {U01 MH098953/MH/NIMH NIH HHS/United States ; U01MH098953/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cell Transdifferentiation/genetics ; Databases, Factual ; Embryonic Stem Cells/cytology/metabolism ; Fibroblasts/cytology/metabolism ; Gene Expression Profiling/*methods ; Internet ; Transcription Factors/genetics/metabolism ; *User-Computer Interface ; }, abstract = {BACKGROUND: Many R packages have been developed for transcriptome analysis but their use often requires familiarity with R and integrating results of different packages requires scripts to wrangle the datatypes. Furthermore, exploratory data analyses often generate multiple derived datasets such as data subsets or data transformations, which can be difficult to track.

RESULTS: Here we present PIVOT, an R-based platform that wraps open source transcriptome analysis packages with a uniform user interface and graphical data management that allows non-programmers to interactively explore transcriptomics data. PIVOT supports more than 40 popular open source packages for transcriptome analysis and provides an extensive set of tools for statistical data manipulations. A graph-based visual interface is used to represent the links between derived datasets, allowing easy tracking of data versions. PIVOT further supports automatic report generation, publication-quality plots, and program/data state saving, such that all analysis can be saved, shared and reproduced.

CONCLUSIONS: PIVOT will allow researchers with broad background to easily access sophisticated transcriptome analysis tools and interactively explore transcriptome datasets.}, } @article {pmid29303698, year = {2018}, author = {Adhikary, S and Bisgaard, M and Nicklas, W and Christensen, H}, title = {Reclassification of Bisgaard taxon 5 as Caviibacterium pharyngocola gen. nov., sp. nov. and Bisgaard taxon 7 as Conservatibacter flavescens gen. nov., sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {643-650}, doi = {10.1099/ijsem.0.002558}, pmid = {29303698}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Guinea Pigs/*microbiology ; Nucleic Acid Hybridization ; Pasteurellaceae/*classification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A total of 29 strains mainly from guinea pigs were investigated by a polyphasic approach that included previously published data. The strains were classified as Bisgaard taxa 5 and 7 by comparison of phenotypic characteristics and the strains showed typical cultural characteristics for members of family Pasteurellaceae and the strains formed two monophyletic groups based on 16S rRNA gene sequence comparison. Partial rpoB sequence analysis as well as published data on DNA-DNA hybridization showed high genotypic relationships within both groups. A new genus with one species, Caviibacterium pharyngocola gen. nov., sp. nov., is proposed to accommodate members of taxon 5 of Bisgaard, whereas members of taxon 7 are proposed as Conservatibacter flavescens gen. nov., sp. nov. The two genera are clearly separated by phenotype from each other and from existing genera of the family Pasteurellaceae. The type strain of Caviibacterium pharyngocola is 7.3T (=CCUG 16493T=DSM 105478T) and the type strain of Conservatibacter flavescens is 7.4T (=CCUG 24852T=DSM 105479T=HIM 794-7T), both were isolated from the pharynx of guinea pigs.}, } @article {pmid29303697, year = {2018}, author = {Park, S and Choi, J and Choi, SJ and Yoon, JH}, title = {Flavobacterium sediminilitoris sp. nov., isolated from a tidal flat.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {630-635}, doi = {10.1099/ijsem.0.002555}, pmid = {29303697}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, facultatively aerobic, motile-by-gliding, non-flagellated and rod-shaped bacterial strain, designated YSM-43T, was isolated from a tidal flat in Yeosu on the South Sea in the Republic of Korea. Strain YSM-43T grew optimally at 30 °C and in the presence of 1.0-2.0 % (w/v) NaCl. A neighbour-joining phylogenetic tree based on 16S rRNA gene sequences showed that strain YSM-43T fell within the clade comprising type strains of Flavobacterium species, clustering with the type strains of Flavobacterium jejuense and Flavobacterium jumunjinense. It exhibited 16S rRNA gene sequence similarity values of 97.20 and 97.15 % to the type strains of F. jejuense and F. jumunjinense, respectively, and of less than 96.59 % to the type strains of the other Flavobacterium species. Strain YSM-43T contained menaquinone-6 as the predominant menaquinone and iso-C15 : 0, iso-C17 : 0 3-OH, iso-C15 : 1 G and iso-C15 : 0 3-OH as the major fatty acids. The major polar lipids were phosphatidylethanolamine and one unidentified lipid. The DNA G+C content of strain YSM-43T was 29.8 mol% and its DNA-DNA relatedness values with type strains of F. jejuense and F. jumunjinense were 13 and 11 %, respectively. The differential phenotypic properties, together with the phylogenetic and genetic data, revealed that strain YSM-43T is separate from other recognized species of the genus Flavobacterium. On the basis of the data presented, strain YSM-43T is considered to represent a novel species of the genus Flavobacterium, for which the name Flavobacteriumsediminilitoris sp. nov. is proposed. The type strain is YSM-43T (=KACC 19435T=KCTC 62142T=NBRC 113020T).}, } @article {pmid29303696, year = {2018}, author = {Bu, JH and Cha, CJ}, title = {Flavobacterium foetidum sp. nov., isolated from ginseng soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {616-622}, doi = {10.1099/ijsem.0.002553}, pmid = {29303696}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Panax/*microbiology ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-staining-negative bacterial strain, designated CJ42T, was isolated from ginseng soil in Anseong, Republic of Korea. Cells were rod-shaped, yellow-pigmented, aerobic and devoid of flagella but showed gliding motility. Strain CJ42T grew optimally at 30 °C and pH 7.0 in the absence of NaCl on tryptic soy agar. Phylogenetic analysis based on the 16S rRNA gene sequence showed that strain CJ42T belonged to the genus Flavobacterium within the family Flavobacteriaceae and was most closely related to Flavobacterium tistrianum KCTC 42679T (97.3 % similarity). Flexirubin-type pigments were produced. The only respiratory quinone was menaquinone 6. The predominant polar lipids were phosphatidylethanolamine, an unknown aminolipid and two unknown lipids. The major fatty acids of strain CJ42T were iso-C15 : 0 and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The G+C content of the genomic DNA was 30.7 mol%. Based on the polyphasic analyses, strain CJ42T represents a novel species in the genus Flavobacterium, for which the name Flavobacteriumfoetidum sp. nov. is proposed. The type strain is CJ42T (=KACC 19302=JCM 32085).}, } @article {pmid29303695, year = {2018}, author = {Chaudhary, DK and Kim, J}, title = {Sphingobacterium terrae sp. nov., isolated from oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {609-615}, doi = {10.1099/ijsem.0.002552}, pmid = {29303695}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nepal ; Nucleic Acid Hybridization ; *Petroleum Pollution ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Sphingobacterium/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A cream-coloured, Gram-stain-negative, non-motile and rod-shaped bacterium, designated strain Brt-FT, was isolated from oil-contaminated soil. Strain Brt-FT was able to grow from 15 to 45 °C, pH 6.5-10.5 and 0-4.5 % (w/v) NaCl concentration. This strain was taxonomically characterized by a polyphasic approach. Based on 16S rRNA gene sequence analysis, strain Brt-FT represented a member of the genus Sphingobacterium and shared highest sequence similarity with Sphingobacterium chuzhouense DH-5T (99.4 %); Sphingobacterium gobiense H7T (95.7 %) and Sphingobacterium arenae H-12T (94.3 %). The only respiratory quinone was menaquinone-7, the major polar lipid was phosphatidylethanolamine and the predominant fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0, and iso-C17 : 0 3-OH. The DNA G+C content was 43.4 mol%. The DNA-DNA relatedness value between strain Brt-FT and S. chuzhouense KCTC 42746T was 35.7 %, which falls below the threshold value of 70 % for the strain to be considered as novel. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain Brt-FT represents a novel species of the genus Sphingobacterium, for which the name Sphingobacteriumterrae sp. nov. is proposed. The type strain is Brt-FT (=KEMB 9005-691T=KACC 19392T=JCM 32159T).}, } @article {pmid29303694, year = {2018}, author = {Bae, SS and Jung, J and Chung, D and Baek, K}, title = {Marinobacterium aestuarii sp. nov., a benzene-degrading marine bacterium isolated from estuary sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {651-656}, doi = {10.1099/ijsem.0.002561}, pmid = {29303694}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Benzene ; DNA, Bacterial/genetics ; *Estuaries ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Oceanospirillaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, motile, flagellated rod-shaped bacterium, designated ST58-10T, was isolated from an estuarine sediment in the Republic of Korea. The strain was able to degrade benzene. Growth of strain ST58-10T was observed at 4-35 °C (optimum, 20-25 °C), pH 5-9 (optimum, pH 7-8) and 1-8 % NaCl (optimum, 3 %). Phylogenetic analyses based on 16S rRNA gene sequences showed that strain ST58-10T formed a phyletic lineage within the genus Marinobacterium of the family Oceanospirillaceae. Strain ST58-10T was most closely related to Marinobacterium profundum PAMC 27536T (99.6 %) and Marinobacterium rhizophilum CL-YJ9T (98.3 %), and to other members of the genus Marinobacterium(94.5-91.5 %). However, the mean value estimated by using the Genome-to-Genome Distance Calculator was 50.6±7.4 % with M. profundum PAMC 27536T and 30.9±2.8 with M. rhizophilum CL-YJ9T, respectively. An average nucleotide identity value was 89.0 % with M. profundum PAMC 27536T and 85.6 % with M. rhizophilum CL-YJ9T, respectively. The major fatty acids of strain ST58-10T were summed feature 3 (comprising C16 : 1ω7c/C16 : 1ω6c), summed feature 8 (comprising C18 : 1 ω7c/C18 : 1ω6c), C16 : 0 and C10 : 0 3-OH, and contained ubiquinone (Q-8) as the sole isoprenoid quinone. Phosphatidylethanolamine, phosphatidylglycerol, three unidentified aminolipids, an unidentified glycolipid and an unidentified lipid were detected as polar lipids. The DNA G+C content of strain ST58-10T was 58.78 mol%. On the basis of the phenotypic, chemotaxonomic and molecular properties, strain ST58-10T represents a novel species of the genus Marinobacterium, for which the name Marinobacterium aestuarii sp. nov. is proposed. The type strain is ST58-10T (=KCTC 52193T=NBRC 112103T).}, } @article {pmid29303693, year = {2018}, author = {Nedashkovskaya, OI and Kim, SG and Balabanova, LA and Zhukova, NV and Bakunina, IY and Mikhailov, VV}, title = {Polaribacter staleyi sp. nov., a polysaccharide-degrading marine bacterium isolated from the red alga Ahnfeltia tobuchiensis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {623-629}, doi = {10.1099/ijsem.0.002554}, pmid = {29303693}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; Polysaccharides ; RNA, Ribosomal, 16S/genetics ; Rhodophyta/*microbiology ; Russia ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, motile by gliding and yellow-pigmented bacterium, designated strain 10Alg 139T, was isolated from the Pacific red alga Ahnfeltiato buchiensis. The phylogenetic analysis based on 16S rRNA gene sequences showed that the novel strain belonged to the genus Polaribacter, a member of the family Flavobacteriaceae, the phylum Bacteroidetes, with highest sequence similarity to Polaribacter butkevichii KMM 3938T (99.3 %) and 93.3-98.6 % to other recognized Polaribacter species. The prevalent fatty acids of strain 10Alg 139T were iso-C15 : 0 3-OH, C15 : 0 3-OH, iso-C15:0, iso-C13 : 0, C15 : 0 and C15 : 1ω6c. The polar lipid profile consisted of the major lipids phosphatidylethanolamine, two unidentified aminolipids and four unidentified lipids. The main respiratory quinone was menaquinone 6. The DNA G+C content of the type strain is 31.8 mol%. The new isolate and the type strains of recognized species of the genus Polaribacter were readily distinguished based on a number of phenotypic characteristics. A combination of the genotypic and phenotypic data showed that the isolate from alga represents a novel species of the genus Polaribacter, for which the name Polaribacterstaleyi sp. nov. is proposed. The type strain is 10Alg 139T (=KCTC 52773T=KMM 6729T).}, } @article {pmid29303692, year = {2018}, author = {Pérez-López, E and Omar, AF and Al-Jamhan, KM and Dumonceaux, TJ}, title = {Molecular identification and characterization of the new 16SrIX-J and cpn60 UT IX-J phytoplasma subgroup associated with chicory bushy stunt disease in Saudi Arabia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {518-522}, doi = {10.1099/ijsem.0.002530}, pmid = {29303692}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Chicory/*microbiology ; DNA, Bacterial/genetics ; *Phylogeny ; Phytoplasma/*classification/genetics/isolation & purification ; Plant Diseases/*microbiology ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S/genetics ; Saudi Arabia ; Sequence Analysis, DNA ; }, abstract = {Chicory (Cichorium intybus) is a perennial plant (Asteraceae) that grows wild in pasture fields in Saudi Arabia. Chicory plants displaying symptoms typically induced by phytoplasmas, such as bushy phenotype and stunt, were observed in the Mulayda region, Qassim governorate, Saudi Arabia. In this study we examined samples taken from three symptomatic chicory plants and confirmed the presence of phytoplasma DNA. Analysis of the 16S rRNA-encoding sequences showed that the plants were infected with a phytoplasma from the pigeon pea witches'-broom group (16SrIX). Sequencing of the 16S rRNA-encoding gene and the partial cpn60 sequence, computer-simulated RFLP analysis, and phylogenetic analysis of both markers revealed that the phytoplasma identified was representative of a new 16SrIX-J and cpn60 UT IX-IJ subgroup. The present study identified chicory plants as a novel host for phytoplasma strains within the pigeon pea witches'-broom phytoplasma group, and expanded the known diversity of this group.}, } @article {pmid29302276, year = {2018}, author = {Cuenca Cambronero, M and Zeis, B and Orsini, L}, title = {Haemoglobin-mediated response to hyper-thermal stress in the keystone species Daphnia magna.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {112-120}, pmid = {29302276}, issn = {1752-4571}, abstract = {Anthropogenic global warming has become a major geological and environmental force driving drastic changes in natural ecosystems. Due to the high thermal conductivity of water and the effects of temperature on metabolic processes, freshwater ecosystems are among the most impacted by these changes. The ability to tolerate changes in temperature may determine species long-term survival and fitness. Therefore, it is critical to identify coping mechanisms to thermal and hyper-thermal stress in aquatic organisms. A central regulatory element compensating for changes in oxygen supply and ambient temperature is the respiratory protein haemoglobin (Hb). Here, we quantify Hb plastic and evolutionary response in Daphnia magna subpopulations resurrected from the sedimentary archive of a lake with known history of increase in average temperature and recurrence of heat waves. By measuring constitutive changes in crude Hb protein content among subpopulations, we assessed evolution of the Hb gene family in response to temperature increase. To quantify the contribution of plasticity in the response of this gene family to hyper-thermal stress, we quantified changes in Hb content in all subpopulations under hyper-thermal stress as compared to nonstressful temperature. Further, we tested competitive abilities of genotypes as a function of their Hb content, constitutive and induced. We found that Hb-rich genotypes have superior competitive abilities as compared to Hb-poor genotypes under hyper-thermal stress after a period of acclimation. These findings suggest that whereas long-term adjustment to higher occurrence of heat waves may require a combination of plasticity and genetic adaptation, plasticity is most likely the coping mechanism to hyper-thermal stress in the short term. Our study suggests that with higher occurrence of heat waves, Hb-rich genotypes may be favoured with potential long-term impact on population genetic diversity.}, } @article {pmid29302275, year = {2018}, author = {Goitom, E and Kilsdonk, LJ and Brans, K and Jansen, M and Lemmens, P and De Meester, L}, title = {Rapid evolution leads to differential population dynamics and top-down control in resurrected Daphnia populations.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {96-111}, pmid = {29302275}, issn = {1752-4571}, abstract = {There is growing evidence of rapid genetic adaptation of natural populations to environmental change, opening the perspective that evolutionary trait change may subsequently impact ecological processes such as population dynamics, community composition, and ecosystem functioning. To study such eco-evolutionary feedbacks in natural populations, however, requires samples across time. Here, we capitalize on a resurrection ecology study that documented rapid and adaptive evolution in a natural population of the water flea Daphnia magna in response to strong changes in predation pressure by fish, and carry out a follow-up mesocosm experiment to test whether the observed genetic changes influence population dynamics and top-down control of phytoplankton. We inoculated populations of the water flea D. magna derived from three time periods of the same natural population known to have genetically adapted to changes in predation pressure in replicate mesocosms and monitored both Daphnia population densities and phytoplankton biomass in the presence and absence of fish. Our results revealed differences in population dynamics and top-down control of algae between mesocosms harboring populations from the time period before, during, and after a peak in fish predation pressure caused by human fish stocking. The differences, however, deviated from our a priori expectations. An S-map approach on time series revealed that the interactions between adults and juveniles strongly impacted the dynamics of populations and their top-down control on algae in the mesocosms, and that the strength of these interactions was modulated by rapid evolution as it occurred in nature. Our study provides an example of an evolutionary response that fundamentally alters the processes structuring population dynamics and impacts ecosystem features.}, } @article {pmid29302274, year = {2018}, author = {Weis, AE}, title = {Detecting the "invisible fraction" bias in resurrection experiments.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {88-95}, pmid = {29302274}, issn = {1752-4571}, abstract = {The resurrection approach is a powerful tool for estimating phenotypic evolution in response to global change. Ancestral generations, revived from dormant propagules, are grown side by side with descendent generations in the same environment. Phenotypic differences between the generations can be attributed to genetic change over time. Project Baseline was established to capitalize on this potential in flowering plants. Project participants collected, froze, and stored seed from 10 or more natural populations of 61 North American plant species. These will be made available in the future for resurrection experiments. One problem with this approach can arise if nonrandom mortality during storage biases the estimate of ancestral mean phenotype, which in turn would bias the estimate of evolutionary change. This bias-known as the "invisible fraction" problem-can arise if seed traits that affect survival during storage and revival are genetically correlated to postemergence traits of interest. The bias is trivial if seed survival is high. Here, I show that with low seed survival, bias can be either trivial or catastrophic. Serious bias arises when (i) most seeds deaths are selective with regard to the seed traits, and (ii) the genetic correlations between the seed and postemergence traits are strong. An invisible fraction bias can be diagnosed in seed collections that are family structured. A correlation between the family mean survival rate and the family mean of a focal postemergence trait indicates that seed mortality was not random with respect to genes affecting the focal trait, biasing the sample mean. Fortunately, family structure was incorporated into the sampling scheme for the Project Baseline collection, which will allow bias detection. New and developing statistical procedures that can incorporate genealogical information into the analysis of resurrection experiments may enable bias correction.}, } @article {pmid29302273, year = {2018}, author = {Lenormand, T and Nougué, O and Jabbour-Zahab, R and Arnaud, F and Dezileau, L and Chevin, LM and Sánchez, MI}, title = {Resurrection ecology in Artemia.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {76-87}, pmid = {29302273}, issn = {1752-4571}, abstract = {Resurrection ecology (RE) is a very powerful approach to address a wide range of question in ecology and evolution. This approach rests on using appropriate model systems, and only few are known to be available. In this study, we show that Artemia has multiple attractive features (short generation time, cyst bank and collections, well-documented phylogeography, and ecology) for a good RE model. We show in detail with a case study how cysts can be recovered from sediments to document the history and dynamics of a biological invasion. We finally discuss with precise examples the many RE possibilities with this model system: adaptation to climate change, to pollution, to parasites, to invaders and evolution of reproductive systems.}, } @article {pmid29302272, year = {2018}, author = {Shoemaker, WR and Lennon, JT}, title = {Evolution with a seed bank: The population genetic consequences of microbial dormancy.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {60-75}, pmid = {29302272}, issn = {1752-4571}, abstract = {Dormancy is a bet-hedging strategy that allows organisms to persist through conditions that are suboptimal for growth and reproduction by entering a reversible state of reduced metabolic activity. Dormancy allows a population to maintain a reservoir of genetic and phenotypic diversity (i.e., a seed bank) that can contribute to the long-term survival of a population. This strategy can be potentially adaptive and has long been of interest to ecologists and evolutionary biologists. However, comparatively little is known about how dormancy influences the fundamental evolutionary forces of genetic drift, mutation, selection, recombination, and gene flow. Here, we investigate how seed banks affect the processes underpinning evolution by reviewing existing theory, implementing novel simulations, and determining how and when dormancy can influence evolution as a population genetic process. We extend our analysis to examine how seed banks can alter macroevolutionary processes, including rates of speciation and extinction. Through the lens of population genetic theory, we can understand the extent that seed banks influence the evolutionary dynamics of microorganisms as well as other taxa.}, } @article {pmid29302271, year = {2018}, author = {Burge, DRL and Edlund, MB and Frisch, D}, title = {Paleolimnology and resurrection ecology: The future of reconstructing the past.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {42-59}, pmid = {29302271}, issn = {1752-4571}, abstract = {Paleolimnologists have utilized lake sediment records to understand historical lake and landscape development, timing and magnitude of environmental change at lake, watershed, regional and global scales, and as historical datasets to target watershed and lake management. Resurrection ecologists have long recognized lake sediments as sources of viable propagules ("seed or egg banks") with which to explore questions of community ecology, ecological response, and evolutionary ecology. Most researchers consider Daphnia as the primary model organism in these efforts, but many other aquatic biota, from viruses to macrophytes, similarly produce viable propagules that are incorporated in the sediment record but have been underutilized in resurrection ecology. The common goals shared by these two disciplines have led to mutualistic and synergistic collaborations-a development that must be encouraged to expand. We give an overview of the achievements of paleolimnology and the reconstruction of environmental history of lakes, review the untapped diversity of aquatic organisms that produce dormant propagules, compare Daphnia as a model of resurrection ecology with other organisms amenable to resurrection studies, especially diatoms, and consider new research directions that represent the nexus of these two fields.}, } @article {pmid29302270, year = {2018}, author = {Houwenhuyse, S and Macke, E and Reyserhove, L and Bulteel, L and Decaestecker, E}, title = {Back to the future in a petri dish: Origin and impact of resurrected microbes in natural populations.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {29-41}, pmid = {29302270}, issn = {1752-4571}, abstract = {Current natural populations face new interactions because of the re-emergence of ancient microbes and viruses. These risks come from the re-emergence of pathogens kept in laboratories or from pathogens that are retained in the permafrost, which become available upon thawing due to climate change. We here focus on the effects of such re-emergence in natural host populations based on evolutionary theory of virulence and long-term studies, which investigate host-pathogen adaptations. Pathogens tend to be locally and temporally adapted to their co-occurring hosts, but when pathogens from a different environment or different time enter the host community, the degree to which a new host-pathogen interaction is a threat will depend on the specific genotypic associations, the time lag between the host and the pathogen, and the interactions with native or recent host and pathogen species. Some insights can be obtained from long-term studies using a resurrection ecology approach. These long-term studies based on time-shift experiments are essential to obtain insight into the mechanisms underlying host-pathogen coevolution at several ecological and temporal scales. As past pathogens and their corresponding host(s) can differ in infectivity and susceptibility, strong reciprocal selective pressures can be induced by the pathogen. These strong selective pressures often result in an escalating arms race, but do not necessarily result in increased infectivity over time. Human health can also be impacted by these resurrected pathogens as the majority of emerging infectious diseases are zoonoses, which are infectious diseases originating from animal populations naturally transmitted to humans. The sanitary risk associated with pathogen emergence from different environments (spatial or temporal) depends on a combination of socioeconomic, environmental, and ecological factors that affect the virulence or the pathogenic potential of microbes and their ability to infect susceptible host populations.}, } @article {pmid29302269, year = {2018}, author = {Franks, SJ and Hamann, E and Weis, AE}, title = {Using the resurrection approach to understand contemporary evolution in changing environments.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {17-28}, pmid = {29302269}, issn = {1752-4571}, abstract = {The resurrection approach of reviving ancestors from stored propagules and comparing them with descendants under common conditions has emerged as a powerful method of detecting and characterizing contemporary evolution. As climatic and other environmental conditions continue to change at a rapid pace, this approach is becoming particularly useful for predicting and monitoring evolutionary responses. We evaluate this approach, explain the advantages and limitations, suggest best practices for implementation, review studies in which this approach has been used, and explore how it can be incorporated into conservation and management efforts. We find that although the approach has thus far been used in a limited number of cases, these studies have provided strong evidence for rapid contemporary adaptive evolution in a variety of systems, particularly in response to anthropogenic environmental change, although it is far from clear that evolution will be able to rescue many populations from extinction given current rates of global changes. We also highlight one effort, known as Project Baseline, to create a collection of stored seeds that can take advantage of the resurrection approach to examine evolutionary responses to environmental change over the coming decades. We conclude that the resurrection approach is a useful tool that could be more widely employed to examine basic questions about evolution in natural populations and to assist in the conservation and management of these populations as they face continued environmental change.}, } @article {pmid29302268, year = {2018}, author = {Ellegaard, M and Godhe, A and Ribeiro, S}, title = {Time capsules in natural sediment archives-Tracking phytoplankton population genetic diversity and adaptation over multidecadal timescales in the face of environmental change.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {11-16}, pmid = {29302268}, issn = {1752-4571}, abstract = {Undisturbed records of resting stages produced in the past and stored in coastal sediments are very valuable to science, because they may provide unique insights into past evolutionary and ecological trajectories. Within marine phytoplankton, multidecadal time series of monoclonal strains germinated from resting stages have been established for diatoms (Skeletonema marinoi) and dinoflagellates (Pentapharsodinium dalei), spanning ca. a century. Phenotypic and genotypic analyses of these time series have revealed effects of past environmental changes on population genetic structure. Future perspectives include direct comparisons of phenotypes and genotypic data of populations, for example, by genomewide assays that can correlate phenotypic trends with genotypes and allele frequencies in temporally separated strains. Besides their usefulness as historical records, "seed" banks of phytoplankton resting stages also have the potential to provide an inoculum that influences present populations through "dispersal from the past" (the storage effect) and are important for adaptation to future environments through their standing genetic diversity.}, } @article {pmid29302267, year = {2018}, author = {Weider, LJ and Jeyasingh, PD and Frisch, D}, title = {Evolutionary aspects of resurrection ecology: Progress, scope, and applications-An overview.}, journal = {Evolutionary applications}, volume = {11}, number = {1}, pages = {3-10}, pmid = {29302267}, issn = {1752-4571}, abstract = {This perspective provides an overview to the Special Issue on Resurrection Ecology (RE). It summarizes the contributions to this Special Issue, and provides background information and future prospects for the use of RE in both basic and applied evolutionary studies.}, } @article {pmid29302016, year = {2018}, author = {Zepeda, L}, title = {The harassment tax.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {126}, doi = {10.1126/science.359.6371.126}, pmid = {29302016}, issn = {1095-9203}, } @article {pmid29302015, year = {2018}, author = {Huang, Y and Mao, K and Chen, X and Sun, MA and Kawabe, T and Li, W and Usher, N and Zhu, J and Urban, JF and Paul, WE and Germain, RN}, title = {S1P-dependent interorgan trafficking of group 2 innate lymphoid cells supports host defense.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {114-119}, doi = {10.1126/science.aam5809}, pmid = {29302015}, issn = {1095-9203}, mesh = {Adaptive Immunity ; Animals ; Cell Proliferation ; Chemotaxis/*immunology ; Female ; Fingolimod Hydrochloride/pharmacology ; Homeodomain Proteins/genetics ; Homeostasis ; *Immunity, Innate ; Immunosuppressive Agents/pharmacology ; Interleukin-17/*immunology ; Intestines/immunology ; Lung/immunology ; Lymphocytes/*immunology ; Lysophospholipids/*immunology ; Mice ; Mice, Inbred C57BL ; Mice, Mutant Strains ; Mucous Membrane/immunology ; Nippostrongylus/*immunology ; Sphingosine/*analogs & derivatives/immunology ; Strongylida Infections/*immunology ; T-Lymphocytes/immunology ; }, abstract = {Innate lymphoid cells (ILCs) are innate counterparts of adaptive T lymphocytes, contributing to host defense, tissue repair, metabolic homeostasis, and inflammatory diseases. ILCs have been considered to be tissue-resident cells, but whether ILCs move between tissue sites during infection has been unclear. We show here that interleukin-25- or helminth-induced inflammatory ILC2s are circulating cells that arise from resting ILC2s residing in intestinal lamina propria. They migrate to diverse tissues based on sphingosine 1-phosphate (S1P)-mediated chemotaxis that promotes lymphatic entry, blood circulation, and accumulation in peripheral sites, including the lung, where they contribute to anti-helminth defense and tissue repair. This ILC2 expansion and migration is a behavioral parallel to the antigen-driven proliferation and migration of adaptive lymphocytes to effector sites and indicates that ILCs complement adaptive immunity by providing both local and distant tissue protection during infection.}, } @article {pmid29302014, year = {2018}, author = {Matson, V and Fessler, J and Bao, R and Chongsuwat, T and Zha, Y and Alegre, ML and Luke, JJ and Gajewski, TF}, title = {The commensal microbiome is associated with anti-PD-1 efficacy in metastatic melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {104-108}, doi = {10.1126/science.aao3290}, pmid = {29302014}, issn = {1095-9203}, support = {R35 CA210098/CA/NCI NIH HHS/United States ; T32 CA009594/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Monoclonal/therapeutic use ; Bifidobacterium longum/classification/genetics/immunology/isolation & purification ; Enterococcus faecium/classification/genetics/immunology/isolation & purification ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; Immunotherapy/*methods ; Melanoma/immunology/*therapy ; Mice ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; RNA, Ribosomal, 16S/genetics ; Skin Neoplasms/immunology/*therapy ; T-Lymphocytes/immunology ; }, abstract = {Anti-PD-1-based immunotherapy has had a major impact on cancer treatment but has only benefited a subset of patients. Among the variables that could contribute to interpatient heterogeneity is differential composition of the patients' microbiome, which has been shown to affect antitumor immunity and immunotherapy efficacy in preclinical mouse models. We analyzed baseline stool samples from metastatic melanoma patients before immunotherapy treatment, through an integration of 16S ribosomal RNA gene sequencing, metagenomic shotgun sequencing, and quantitative polymerase chain reaction for selected bacteria. A significant association was observed between commensal microbial composition and clinical response. Bacterial species more abundant in responders included Bifidobacterium longum, Collinsella aerofaciens, and Enterococcus faecium. Reconstitution of germ-free mice with fecal material from responding patients could lead to improved tumor control, augmented T cell responses, and greater efficacy of anti-PD-L1 therapy. Our results suggest that the commensal microbiome may have a mechanistic impact on antitumor immunity in human cancer patients.}, } @article {pmid29302013, year = {2018}, author = {Ramsuran, V and Naranbhai, V and Horowitz, A and Qi, Y and Martin, MP and Yuki, Y and Gao, X and Walker-Sperling, V and Del Prete, GQ and Schneider, DK and Lifson, JD and Fellay, J and Deeks, SG and Martin, JN and Goedert, JJ and Wolinsky, SM and Michael, NL and Kirk, GD and Buchbinder, S and Haas, D and Ndung'u, T and Goulder, P and Parham, P and Walker, BD and Carlson, JM and Carrington, M}, title = {Elevated HLA-A expression impairs HIV control through inhibition of NKG2A-expressing cells.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {86-90}, pmid = {29302013}, issn = {1095-9203}, support = {U01 AI035039/AI/NIAID NIH HHS/United States ; UM1 AI068636/AI/NIAID NIH HHS/United States ; UM1 AI069496/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Alleles ; CD4 Lymphocyte Count ; Cohort Studies ; HIV/*immunology ; HIV Infections/drug therapy/genetics/*immunology ; HLA Antigens/genetics/*metabolism ; Humans ; Killer Cells, Natural/*immunology ; Ligands ; NK Cell Lectin-Like Receptor Subfamily C/antagonists & inhibitors/genetics/*metabolism ; Protein Sorting Signals ; Viremia/immunology ; }, abstract = {The highly polymorphic human leukocyte antigen (HLA) locus encodes cell surface proteins that are critical for immunity. HLA-A expression levels vary in an allele-dependent manner, diversifying allele-specific effects beyond peptide-binding preference. Analysis of 9763 HIV-infected individuals from 21 cohorts shows that higher HLA-A levels confer poorer control of HIV. Elevated HLA-A expression provides enhanced levels of an HLA-A-derived signal peptide that specifically binds and determines expression levels of HLA-E, the ligand for the inhibitory NKG2A natural killer (NK) cell receptor. HLA-B haplotypes that favor NKG2A-mediated NK cell licensing (i.e., education) exacerbate the deleterious effect of high HLA-A on HIV control, consistent with NKG2A-mediated inhibition impairing NK cell clearance of HIV-infected targets. Therapeutic blockade of HLA-E:NKG2A interaction may yield benefit in HIV disease.}, } @article {pmid29302012, year = {2018}, author = {Bay, RA and Harrigan, RJ and Underwood, VL and Gibbs, HL and Smith, TB and Ruegg, K}, title = {Genomic signals of selection predict climate-driven population declines in a migratory bird.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {83-86}, doi = {10.1126/science.aan4380}, pmid = {29302012}, issn = {1095-9203}, mesh = {Acclimatization/*genetics ; *Animal Migration ; Animals ; Biodiversity ; Breeding ; *Climate Change ; Genome ; Passeriformes/*genetics ; Population Dynamics ; Songbirds/*genetics ; }, abstract = {The ongoing loss of biodiversity caused by rapid climatic shifts requires accurate models for predicting species' responses. Despite evidence that evolutionary adaptation could mitigate climate change impacts, evolution is rarely integrated into predictive models. Integrating population genomics and environmental data, we identified genomic variation associated with climate across the breeding range of the migratory songbird, yellow warbler (Setophaga petechia). Populations requiring the greatest shifts in allele frequencies to keep pace with future climate change have experienced the largest population declines, suggesting that failure to adapt may have already negatively affected populations. Broadly, our study suggests that the integration of genomic adaptation can increase the accuracy of future species distribution models and ultimately guide more effective mitigation efforts.}, } @article {pmid29302011, year = {2018}, author = {Hughes, TP and Anderson, KD and Connolly, SR and Heron, SF and Kerry, JT and Lough, JM and Baird, AH and Baum, JK and Berumen, ML and Bridge, TC and Claar, DC and Eakin, CM and Gilmour, JP and Graham, NAJ and Harrison, H and Hobbs, JA and Hoey, AS and Hoogenboom, M and Lowe, RJ and McCulloch, MT and Pandolfi, JM and Pratchett, M and Schoepf, V and Torda, G and Wilson, SK}, title = {Spatial and temporal patterns of mass bleaching of corals in the Anthropocene.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {80-83}, doi = {10.1126/science.aan8048}, pmid = {29302011}, issn = {1095-9203}, mesh = {Animals ; *Anthozoa ; *Coral Reefs ; *El Nino-Southern Oscillation ; *Global Warming ; Seawater ; }, abstract = {Tropical reef systems are transitioning to a new era in which the interval between recurrent bouts of coral bleaching is too short for a full recovery of mature assemblages. We analyzed bleaching records at 100 globally distributed reef locations from 1980 to 2016. The median return time between pairs of severe bleaching events has diminished steadily since 1980 and is now only 6 years. As global warming has progressed, tropical sea surface temperatures are warmer now during current La Niña conditions than they were during El Niño events three decades ago. Consequently, as we transition to the Anthropocene, coral bleaching is occurring more frequently in all El Niño-Southern Oscillation phases, increasing the likelihood of annual bleaching in the coming decades.}, } @article {pmid29302010, year = {2018}, author = {Wu, S and Fatemi, V and Gibson, QD and Watanabe, K and Taniguchi, T and Cava, RJ and Jarillo-Herrero, P}, title = {Observation of the quantum spin Hall effect up to 100 kelvin in a monolayer crystal.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {76-79}, doi = {10.1126/science.aan6003}, pmid = {29302010}, issn = {1095-9203}, abstract = {A variety of monolayer crystals have been proposed to be two-dimensional topological insulators exhibiting the quantum spin Hall effect (QSHE), possibly even at high temperatures. Here we report the observation of the QSHE in monolayer tungsten ditelluride (WTe2) at temperatures up to 100 kelvin. In the short-edge limit, the monolayer exhibits the hallmark transport conductance, ~e2/h per edge, where e is the electron charge and h is Planck's constant. Moreover, a magnetic field suppresses the conductance, and the observed Zeeman-type gap indicates the existence of a Kramers degenerate point and the importance of time-reversal symmetry for protection from elastic backscattering. Our results establish the QSHE at temperatures much higher than in semiconductor heterostructures and allow for exploring topological phases in atomically thin crystals.}, } @article {pmid29302009, year = {2018}, author = {Schneider, FRN and Sana, H and Evans, CJ and Bestenlehner, JM and Castro, N and Fossati, L and Gräfener, G and Langer, N and Ramírez-Agudelo, OH and Sabín-Sanjulián, C and Simón-Díaz, S and Tramper, F and Crowther, PA and de Koter, A and de Mink, SE and Dufton, PL and Garcia, M and Gieles, M and Hénault-Brunet, V and Herrero, A and Izzard, RG and Kalari, V and Lennon, DJ and Maíz Apellániz, J and Markova, N and Najarro, F and Podsiadlowski, P and Puls, J and Taylor, WD and van Loon, JT and Vink, JS and Norman, C}, title = {An excess of massive stars in the local 30 Doradus starburst.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {69-71}, doi = {10.1126/science.aan0106}, pmid = {29302009}, issn = {1095-9203}, support = {//European Research Council/International ; }, abstract = {The 30 Doradus star-forming region in the Large Magellanic Cloud is a nearby analog of large star-formation events in the distant universe. We determined the recent formation history and the initial mass function (IMF) of massive stars in 30 Doradus on the basis of spectroscopic observations of 247 stars more massive than 15 solar masses ([Formula: see text]). The main episode of massive star formation began about 8 million years (My) ago, and the star-formation rate seems to have declined in the last 1 My. The IMF is densely sampled up to 200 [Formula: see text] and contains 32 ± 12% more stars above 30 [Formula: see text] than predicted by a standard Salpeter IMF. In the mass range of 15 to 200 [Formula: see text], the IMF power-law exponent is [Formula: see text], shallower than the Salpeter value of 2.35.}, } @article {pmid29302008, year = {2018}, author = {Acome, E and Mitchell, SK and Morrissey, TG and Emmett, MB and Benjamin, C and King, M and Radakovitz, M and Keplinger, C}, title = {Hydraulically amplified self-healing electrostatic actuators with muscle-like performance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {61-65}, doi = {10.1126/science.aao6139}, pmid = {29302008}, issn = {1095-9203}, abstract = {Existing soft actuators have persistent challenges that restrain the potential of soft robotics, highlighting a need for soft transducers that are powerful, high-speed, efficient, and robust. We describe a class of soft actuators, termed hydraulically amplified self-healing electrostatic (HASEL) actuators, which harness a mechanism that couples electrostatic and hydraulic forces to achieve a variety of actuation modes. We introduce prototypical designs of HASEL actuators and demonstrate their robust, muscle-like performance as well as their ability to repeatedly self-heal after dielectric breakdown-all using widely available materials and common fabrication techniques. A soft gripper handling delicate objects and a self-sensing artificial muscle powering a robotic arm illustrate the wide potential of HASEL actuators for next-generation soft robotic devices.}, } @article {pmid29302007, year = {2018}, author = {Yin, D and Schwarz, EM and Thomas, CG and Felde, RL and Korf, IF and Cutter, AD and Schartner, CM and Ralston, EJ and Meyer, BJ and Haag, ES}, title = {Rapid genome shrinkage in a self-fertile nematode reveals sperm competition proteins.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {55-61}, pmid = {29302007}, issn = {1095-9203}, support = {R01 GM030702/GM/NIGMS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; R37 GM030702/GM/NIGMS NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; R01 GM079414/GM/NIGMS NIH HHS/United States ; R21 AI111173/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis/classification/*genetics ; Exons ; Genome, Helminth ; Glycoproteins/*genetics ; Helminth Proteins/*genetics ; Hermaphroditic Organisms/*genetics ; INDEL Mutation ; Introns ; Male ; Phylogeny ; Proteome/genetics ; Self-Fertilization/*genetics ; Spermatozoa/*metabolism ; }, abstract = {To reveal impacts of sexual mode on genome content, we compared chromosome-scale assemblies of the outcrossing nematode Caenorhabditis nigoni to its self-fertile sibling species, C. briggsaeC. nigoni's genome resembles that of outcrossing relatives but encodes 31% more protein-coding genes than C. briggsaeC. nigoni genes lacking C. briggsae orthologs were disproportionately small and male-biased in expression. These include the male secreted short (mss) gene family, which encodes sperm surface glycoproteins conserved only in outcrossing species. Sperm from mss-null males of outcrossing C. remanei failed to compete with wild-type sperm, despite normal fertility in noncompetitive mating. Restoring mss to C. briggsae males was sufficient to enhance sperm competitiveness. Thus, sex has a pervasive influence on genome content that can be used to identify sperm competition factors.}, } @article {pmid29302006, year = {2018}, author = {Gruszczyk, J and Kanjee, U and Chan, LJ and Menant, S and Malleret, B and Lim, NTY and Schmidt, CQ and Mok, YF and Lin, KM and Pearson, RD and Rangel, G and Smith, BJ and Call, MJ and Weekes, MP and Griffin, MDW and Murphy, JM and Abraham, J and Sriprawat, K and Menezes, MJ and Ferreira, MU and Russell, B and Renia, L and Duraisingh, MT and Tham, WH}, title = {Transferrin receptor 1 is a reticulocyte-specific receptor for Plasmodium vivax.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {48-55}, pmid = {29302006}, issn = {1095-9203}, support = {208693//Wellcome Trust/United Kingdom ; /HHMI/Howard Hughes Medical Institute/United States ; 108070//Wellcome Trust/United Kingdom ; 206194//Wellcome Trust/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; //CIHR/Canada ; 090770//Wellcome Trust/United Kingdom ; //Wellcome Trust/United Kingdom ; }, mesh = {Antigens, CD/genetics/*metabolism ; Crystallography, X-Ray ; Gene Knockdown Techniques ; Host-Parasite Interactions ; Humans ; Malaria, Vivax/*metabolism/*parasitology ; Membrane Proteins/*chemistry/genetics/metabolism/ultrastructure ; Plasmodium vivax/metabolism/*pathogenicity ; Protein Domains ; Protozoan Proteins/*chemistry/genetics/metabolism/ultrastructure ; Receptors, Transferrin/genetics/*metabolism ; Reticulocytes/*parasitology ; }, abstract = {Plasmodium vivax shows a strict host tropism for reticulocytes. We identified transferrin receptor 1 (TfR1) as the receptor for P. vivax reticulocyte-binding protein 2b (PvRBP2b). We determined the structure of the N-terminal domain of PvRBP2b involved in red blood cell binding, elucidating the molecular basis for TfR1 recognition. We validated TfR1 as the biological target of PvRBP2b engagement by means of TfR1 expression knockdown analysis. TfR1 mutant cells deficient in PvRBP2b binding were refractory to invasion of P. vivax but not to invasion of P. falciparum Using Brazilian and Thai clinical isolates, we show that PvRBP2b monoclonal antibodies that inhibit reticulocyte binding also block P. vivax entry into reticulocytes. These data show that TfR1-PvRBP2b invasion pathway is critical for the recognition of reticulocytes during P. vivax invasion.}, } @article {pmid29302005, year = {2018}, author = {Zivin, JG and Neidell, M}, title = {Air pollution's hidden impacts.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {39-40}, doi = {10.1126/science.aap7711}, pmid = {29302005}, issn = {1095-9203}, mesh = {Air Pollution/*economics ; Humans ; }, } @article {pmid29302004, year = {2018}, author = {Carpick, RW}, title = {The contact sport of rough surfaces.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {38}, doi = {10.1126/science.aaq1814}, pmid = {29302004}, issn = {1095-9203}, } @article {pmid29302003, year = {2018}, author = {Mjösberg, J and Rao, A}, title = {Lung inflammation originating in the gut.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {36-37}, doi = {10.1126/science.aar4301}, pmid = {29302003}, issn = {1095-9203}, mesh = {*Gastrointestinal Tract ; Inflammation ; *Lung ; *Pneumonia ; }, } @article {pmid29302002, year = {2018}, author = {Boetius, A and Haeckel, M}, title = {Mind the seafloor.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {34-36}, doi = {10.1126/science.aap7301}, pmid = {29302002}, issn = {1095-9203}, mesh = {*Biota ; *Conservation of Natural Resources ; *Mining ; Oceans and Seas ; }, } @article {pmid29302001, year = {2018}, author = {Jobin, C}, title = {Precision medicine using microbiota.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {32-34}, doi = {10.1126/science.aar2946}, pmid = {29302001}, issn = {1095-9203}, support = {R01 DK073338/DK/NIDDK NIH HHS/United States ; }, mesh = {Humans ; *Microbiota ; *Precision Medicine ; }, } @article {pmid29302000, year = {2018}, author = {Saldivar, JC and Cimprich, KA}, title = {A new mitotic activity comes into focus.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {30-31}, doi = {10.1126/science.aar4799}, pmid = {29302000}, issn = {1095-9203}, support = {R01 ES016486/ES/NIEHS NIH HHS/United States ; R01 GM119334/GM/NIGMS NIH HHS/United States ; }, mesh = {Humans ; *Mitosis ; *Spindle Apparatus ; }, } @article {pmid29301999, year = {2018}, author = {Fitzpatrick, MJ and Edelsparre, AH}, title = {The genomics of climate change.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {29-30}, doi = {10.1126/science.aar3920}, pmid = {29301999}, issn = {1095-9203}, mesh = {*Climate Change ; *Genomics ; Humans ; }, } @article {pmid29301998, year = {2018}, author = {Olmeta-Schult, F and Segal, LM and Tyner, S and Moon, TA and Chow, RD and Chakrabarty, P and Pacesa, M and Podgornaia, AI and Chen, J and Singh, B and Cao, B and Sidhu, RRS and Tan, BWQ and Sood, P and Parker, S and Scult, MA and Van Haute, D and Konstantinides, N and Schwendimann, BA and Srivastava, S and Fiorenza, R and Dutton-Regester, K and Hale, R and Polat, EO and Lau, E and Mayer, AL and White, ER}, title = {NextGen VOICES: Research resolutions.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {26-28}, doi = {10.1126/science.aar7504}, pmid = {29301998}, issn = {1095-9203}, support = {F32 HL139045/HL/NHLBI NIH HHS/United States ; }, } @article {pmid29301997, year = {2018}, author = {Stone, R}, title = {Weapons in waiting.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {24}, doi = {10.1126/science.359.6371.24}, pmid = {29301997}, issn = {1095-9203}, mesh = {Antidotes/*chemistry ; *Chemical Terrorism ; Chemical Warfare Agents/chemistry/*poisoning ; *Drug Design ; Fentanyl/analogs & derivatives/poisoning ; Humans ; Moscow ; Piperidines/poisoning ; Remifentanil ; United States ; }, } @article {pmid29301996, year = {2018}, author = {Stone, R}, title = {How to defeat a nerve agent.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {23}, doi = {10.1126/science.359.6371.23}, pmid = {29301996}, issn = {1095-9203}, mesh = {Anticonvulsants ; Antidotes/administration & dosage/*chemistry ; Humans ; Military Personnel ; Nerve Agents/*chemistry/toxicity ; Oximes/administration & dosage/*chemistry ; Seizures/chemically induced/drug therapy ; United States ; }, } @article {pmid29301995, year = {2018}, author = {Stone, R}, title = {Chemical martyrs.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {20-25}, doi = {10.1126/science.359.6371.20}, pmid = {29301995}, issn = {1095-9203}, mesh = {Chemical Warfare Agents/*toxicity ; Humans ; Iran ; Iraq ; }, } @article {pmid29301994, year = {2018}, author = {Clery, D}, title = {Earth-based planet finders power up.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {18-19}, doi = {10.1126/science.359.6371.18}, pmid = {29301994}, issn = {1095-9203}, } @article {pmid29301993, year = {2018}, author = {Kupferschmidt, K}, title = {Germany steps up to the plate in global health.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {17-18}, doi = {10.1126/science.359.6371.17}, pmid = {29301993}, issn = {1095-9203}, mesh = {Germany ; Global Health/*trends ; Humans ; }, } @article {pmid29301992, year = {2018}, author = {Hand, E}, title = {Mars methane rises and falls with the seasons.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {16-17}, doi = {10.1126/science.359.6371.16}, pmid = {29301992}, issn = {1095-9203}, } @article {pmid29301991, year = {2018}, author = {Kaiser, J}, title = {Cancer institute head touts big data and basic research.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {15}, doi = {10.1126/science.359.6371.15}, pmid = {29301991}, issn = {1095-9203}, mesh = {Biomedical Research/*trends ; Budgets ; Data Mining/*trends ; Humans ; Machine Learning ; *National Cancer Institute (U.S.) ; Neoplasms/*therapy ; United States ; }, } @article {pmid29301990, year = {2018}, author = {Price, M}, title = {Americas peopled in a single wave, ancient genome reveals.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {14}, doi = {10.1126/science.359.6371.14}, pmid = {29301990}, issn = {1095-9203}, mesh = {Alaska ; Asia ; *DNA, Ancient ; *Genome, Human ; *Human Migration ; Humans ; Infant ; }, } @article {pmid29301989, year = {2018}, author = {Wadman, M}, title = {Watching the teen brain grow.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {13-14}, doi = {10.1126/science.359.6371.13}, pmid = {29301989}, issn = {1095-9203}, mesh = {Adolescent ; *Adolescent Development ; Brain/anatomy & histology/diagnostic imaging/*growth & development ; Child ; *Child Development ; Humans ; Magnetic Resonance Imaging ; }, } @article {pmid29301988, year = {2018}, author = {}, title = {What's coming up in 2018.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {10-12}, doi = {10.1126/science.359.6371.10}, pmid = {29301988}, issn = {1095-9203}, } @article {pmid29301987, year = {2018}, author = {Berg, J}, title = {Progress on reproducibility.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {9}, doi = {10.1126/science.aar8654}, pmid = {29301987}, issn = {1095-9203}, } @article {pmid29301986, year = {2018}, author = {Breitburg, D and Levin, LA and Oschlies, A and Grégoire, M and Chavez, FP and Conley, DJ and Garçon, V and Gilbert, D and Gutiérrez, D and Isensee, K and Jacinto, GS and Limburg, KE and Montes, I and Naqvi, SWA and Pitcher, GC and Rabalais, NN and Roman, MR and Rose, KA and Seibel, BA and Telszewski, M and Yasuhara, M and Zhang, J}, title = {Declining oxygen in the global ocean and coastal waters.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {}, doi = {10.1126/science.aam7240}, pmid = {29301986}, issn = {1095-9203}, mesh = {Adaptation, Biological ; Animals ; Aquatic Organisms ; Conservation of Natural Resources ; *Environmental Monitoring ; Fisheries ; *Global Warming ; Oceans and Seas ; Oxygen/*analysis ; Seawater/*chemistry ; }, abstract = {Oxygen is fundamental to life. Not only is it essential for the survival of individual animals, but it regulates global cycles of major nutrients and carbon. The oxygen content of the open ocean and coastal waters has been declining for at least the past half-century, largely because of human activities that have increased global temperatures and nutrients discharged to coastal waters. These changes have accelerated consumption of oxygen by microbial respiration, reduced solubility of oxygen in water, and reduced the rate of oxygen resupply from the atmosphere to the ocean interior, with a wide range of biological and ecological consequences. Further research is needed to understand and predict long-term, global- and regional-scale oxygen changes and their effects on marine and estuarine fisheries and ecosystems.}, } @article {pmid29301985, year = {2018}, author = {Franzmann, TM and Jahnel, M and Pozniakovsky, A and Mahamid, J and Holehouse, AS and Nüske, E and Richter, D and Baumeister, W and Grill, SW and Pappu, RV and Hyman, AA and Alberti, S}, title = {Phase separation of a yeast prion protein promotes cellular fitness.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {}, doi = {10.1126/science.aao5654}, pmid = {29301985}, issn = {1095-9203}, support = {R01 NS056114/NS/NINDS NIH HHS/United States ; }, mesh = {Catalytic Domain ; Hydrogen-Ion Concentration ; Peptide Termination Factors/chemistry/*metabolism ; Phase Transition ; Prion Proteins/chemistry/*metabolism ; Saccharomyces cerevisiae/cytology/*metabolism ; Saccharomyces cerevisiae Proteins/chemistry/*metabolism ; *Stress, Physiological ; }, abstract = {Despite the important role of prion domains in neurodegenerative disease, their physiological function has remained enigmatic. Previous work with yeast prions has defined prion domains as sequences that form self-propagating aggregates. Here, we uncovered an unexpected function of the canonical yeast prion protein Sup35. In stressed conditions, Sup35 formed protective gels via pH-regulated liquid-like phase separation followed by gelation. Phase separation was mediated by the N-terminal prion domain and regulated by the adjacent pH sensor domain. Phase separation promoted yeast cell survival by rescuing the essential Sup35 translation factor from stress-induced damage. Thus, prion-like domains represent conserved environmental stress sensors that facilitate rapid adaptation in unstable environments by modifying protein phase behavior.}, } @article {pmid29301968, year = {2018}, author = {Kunjapur, AM and Stork, DA and Kuru, E and Vargas-Rodriguez, O and Landon, M and Söll, D and Church, GM}, title = {Engineering posttranslational proofreading to discriminate nonstandard amino acids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {619-624}, pmid = {29301968}, issn = {1091-6490}, support = {R01 GM022854/GM/NIGMS NIH HHS/United States ; R35 GM122560/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acids/*metabolism ; Aminobiphenyl Compounds/metabolism ; Archaeal Proteins/genetics/*metabolism ; Escherichia coli/genetics/metabolism ; Methanocaldococcus/*enzymology/genetics ; *Protein Biosynthesis ; Protein Engineering ; Protein Processing, Post-Translational ; Proteolysis ; Tyrosine-tRNA Ligase/genetics/*metabolism ; }, abstract = {Incorporation of nonstandard amino acids (nsAAs) leads to chemical diversification of proteins, which is an important tool for the investigation and engineering of biological processes. However, the aminoacyl-tRNA synthetases crucial for this process are polyspecific in regard to nsAAs and standard amino acids. Here, we develop a quality control system called "posttranslational proofreading" to more accurately and rapidly evaluate nsAA incorporation. We achieve this proofreading by hijacking a natural pathway of protein degradation known as the N-end rule, which regulates the lifespan of a protein based on its amino-terminal residue. We find that proteins containing certain desired N-terminal nsAAs have much longer half-lives compared with those proteins containing undesired amino acids. We use the posttranslational proofreading system to further evolve a Methanocaldococcus jannaschii tyrosyl-tRNA synthetase (TyrRS) variant and a tRNATyr species for improved specificity of the nsAA biphenylalanine in vitro and in vivo. Our newly evolved biphenylalanine incorporation machinery enhances the biocontainment and growth of genetically engineered Escherichia coli strains that depend on biphenylalanine incorporation. Finally, we show that our posttranslational proofreading system can be designed for incorporation of other nsAAs by rational engineering of the ClpS protein, which mediates the N-end rule. Taken together, our posttranslational proofreading system for in vivo protein sequence verification presents an alternative paradigm for molecular recognition of amino acids and is a major advance in our ability to accurately expand the genetic code.}, } @article {pmid29301967, year = {2018}, author = {Laenen, B and Tedder, A and Nowak, MD and Toräng, P and Wunder, J and Wötzel, S and Steige, KA and Kourmpetis, Y and Odong, T and Drouzas, AD and Bink, MCAM and Ågren, J and Coupland, G and Slotte, T}, title = {Demography and mating system shape the genome-wide impact of purifying selection in Arabis alpina.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {816-821}, pmid = {29301967}, issn = {1091-6490}, mesh = {Arabis/*genetics ; Europe ; Geography ; Mutation ; Polymorphism, Single Nucleotide ; *Selection, Genetic ; *Self-Fertilization ; Whole Genome Sequencing ; }, abstract = {Plant mating systems have profound effects on levels and structuring of genetic variation and can affect the impact of natural selection. Although theory predicts that intermediate outcrossing rates may allow plants to prevent accumulation of deleterious alleles, few studies have empirically tested this prediction using genomic data. Here, we study the effect of mating system on purifying selection by conducting population-genomic analyses on whole-genome resequencing data from 38 European individuals of the arctic-alpine crucifer Arabis alpina We find that outcrossing and mixed-mating populations maintain genetic diversity at similar levels, whereas highly self-fertilizing Scandinavian A. alpina show a strong reduction in genetic diversity, most likely as a result of a postglacial colonization bottleneck. We further find evidence for accumulation of genetic load in highly self-fertilizing populations, whereas the genome-wide impact of purifying selection does not differ greatly between mixed-mating and outcrossing populations. Our results demonstrate that intermediate levels of outcrossing may allow efficient selection against harmful alleles, whereas demographic effects can be important for relaxed purifying selection in highly selfing populations. Thus, mating system and demography shape the impact of purifying selection on genomic variation in A. alpina These results are important for an improved understanding of the evolutionary consequences of mating system variation and the maintenance of mixed-mating strategies.}, } @article {pmid29301966, year = {2018}, author = {Dunn, CW and Zapata, F and Munro, C and Siebert, S and Hejnol, A}, title = {Pairwise comparisons across species are problematic when analyzing functional genomic data.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E409-E417}, pmid = {29301966}, issn = {1091-6490}, mesh = {Algorithms ; Animals ; Evolution, Molecular ; Gene Expression/*physiology ; Genomics/*methods ; Phylogeny ; Software ; Species Specificity ; Vertebrates/genetics/*metabolism ; }, abstract = {There is considerable interest in comparing functional genomic data across species. One goal of such work is to provide an integrated understanding of genome and phenotype evolution. Most comparative functional genomic studies have relied on multiple pairwise comparisons between species, an approach that does not incorporate information about the evolutionary relationships among species. The statistical problems that arise from not considering these relationships can lead pairwise approaches to the wrong conclusions and are a missed opportunity to learn about biology that can only be understood in an explicit phylogenetic context. Here, we examine two recently published studies that compare gene expression across species with pairwise methods, and find reason to question the original conclusions of both. One study interpreted pairwise comparisons of gene expression as support for the ortholog conjecture, the hypothesis that orthologs tend to have more similar attributes (expression in this case) than paralogs. The other study interpreted pairwise comparisons of embryonic gene expression across distantly related animals as evidence for a distinct evolutionary process that gave rise to phyla. In each study, distinct patterns of pairwise similarity among species were originally interpreted as evidence of particular evolutionary processes, but instead, we find that they reflect species relationships. These reanalyses concretely show the inadequacy of pairwise comparisons for analyzing functional genomic data across species. It will be critical to adopt phylogenetic comparative methods in future functional genomic work. Fortunately, phylogenetic comparative biology is also a rapidly advancing field with many methods that can be directly applied to functional genomic data.}, } @article {pmid29301965, year = {2018}, author = {Crouch, DJM and Winney, B and Koppen, WP and Christmas, WJ and Hutnik, K and Day, T and Meena, D and Boumertit, A and Hysi, P and Nessa, A and Spector, TD and Kittler, J and Bodmer, WF}, title = {Genetics of the human face: Identification of large-effect single gene variants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E676-E685}, pmid = {29301965}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 088262/Z/09/Z//Wellcome Trust/United Kingdom ; //Department of Health/United Kingdom ; }, mesh = {Cadherins/*genetics ; *Face ; Female ; Humans ; Male ; Membrane Proteins/*genetics ; Polymorphism, Single Nucleotide ; Principal Component Analysis ; Proprotein Convertases/*genetics ; Quantitative Trait, Heritable ; Serine Endopeptidases/*genetics ; }, abstract = {To discover specific variants with relatively large effects on the human face, we have devised an approach to identifying facial features with high heritability. This is based on using twin data to estimate the additive genetic value of each point on a face, as provided by a 3D camera system. In addition, we have used the ethnic difference between East Asian and European faces as a further source of face genetic variation. We use principal components (PCs) analysis to provide a fine definition of the surface features of human faces around the eyes and of the profile, and chose upper and lower 10% extremes of the most heritable PCs for looking for genetic associations. Using this strategy for the analysis of 3D images of 1,832 unique volunteers from the well-characterized People of the British Isles study and 1,567 unique twin images from the TwinsUK cohort, together with genetic data for 500,000 SNPs, we have identified three specific genetic variants with notable effects on facial profiles and eyes.}, } @article {pmid29301964, year = {2018}, author = {Lo, NC and Gurarie, D and Yoon, N and Coulibaly, JT and Bendavid, E and Andrews, JR and King, CH}, title = {Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E584-E591}, pmid = {29301964}, issn = {1091-6490}, mesh = {Animals ; Computer Simulation ; Cost-Benefit Analysis ; Humans ; Kenya ; *Models, Economic ; Schistosomiasis/economics/*prevention & control/transmission ; *Snails ; }, abstract = {Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA.}, } @article {pmid29301962, year = {2018}, author = {Wild, R and Kowal, J and Eyring, J and Ngwa, EM and Aebi, M and Locher, KP}, title = {Structure of the yeast oligosaccharyltransferase complex gives insight into eukaryotic N-glycosylation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {545-550}, doi = {10.1126/science.aar5140}, pmid = {29301962}, issn = {1095-9203}, mesh = {Catalytic Domain ; Conserved Sequence ; Cryoelectron Microscopy ; Glycosylation ; Hexosyltransferases/*chemistry/ultrastructure ; Membrane Proteins/*chemistry/ultrastructure ; Multienzyme Complexes/*chemistry/ultrastructure ; Oxidation-Reduction ; Saccharomyces cerevisiae Proteins/*chemistry/ultrastructure ; Substrate Specificity ; }, abstract = {Oligosaccharyltransferase (OST) is an essential membrane protein complex in the endoplasmic reticulum, where it transfers an oligosaccharide from a dolichol-pyrophosphate-activated donor to glycosylation sites of secretory proteins. Here we describe the atomic structure of yeast OST determined by cryo-electron microscopy, revealing a conserved subunit arrangement. The active site of the catalytic STT3 subunit points away from the center of the complex, allowing unhindered access to substrates. The dolichol-pyrophosphate moiety binds to a lipid-exposed groove of STT3, whereas two noncatalytic subunits and an ordered N-glycan form a membrane-proximal pocket for the oligosaccharide. The acceptor polypeptide site faces an oxidoreductase domain in stand-alone OST complexes or is immediately adjacent to the translocon, suggesting how eukaryotic OSTs efficiently glycosylate a large number of polypeptides before their folding.}, } @article {pmid29301961, year = {2018}, author = {Zhan, X and Yan, C and Zhang, X and Lei, J and Shi, Y}, title = {Structure of a human catalytic step I spliceosome.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {537-545}, doi = {10.1126/science.aar6401}, pmid = {29301961}, issn = {1095-9203}, mesh = {Amino Acid Sequence ; Biocatalysis ; Catalytic Domain ; Cryoelectron Microscopy ; DEAD-box RNA Helicases/*chemistry/ultrastructure ; Humans ; Models, Molecular ; *RNA Splicing ; RNA Splicing Factors/*chemistry/ultrastructure ; Saccharomyces cerevisiae Proteins/chemistry/ultrastructure ; Spliceosomes/*chemistry/ultrastructure ; }, abstract = {Splicing by the spliceosome involves branching and exon ligation. The branching reaction leads to the formation of the catalytic step I spliceosome (C complex). Here we report the cryo-electron microscopy structure of the human C complex at an average resolution of 4.1 angstroms. Compared with the Saccharomyces cerevisiae C complex, the human complex contains 11 additional proteins. The step I splicing factors CCDC49 and CCDC94 (Cwc25 and Yju2 in S. cerevisiae, respectively) closely interact with the DEAH-family adenosine triphosphatase/helicase Prp16 and bridge the gap between Prp16 and the active-site RNA elements. These features, together with structural comparison of the human C and C* complexes, provide mechanistic insights into ribonucleoprotein remodeling and allow the proposition of a working mechanism for the C-to-C* transition.}, } @article {pmid29301960, year = {2018}, author = {Miao, D and Margolis, CA and Gao, W and Voss, MH and Li, W and Martini, DJ and Norton, C and Bossé, D and Wankowicz, SM and Cullen, D and Horak, C and Wind-Rotolo, M and Tracy, A and Giannakis, M and Hodi, FS and Drake, CG and Ball, MW and Allaf, ME and Snyder, A and Hellmann, MD and Ho, T and Motzer, RJ and Signoretti, S and Kaelin, WG and Choueiri, TK and Van Allen, EM}, title = {Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {801-806}, pmid = {29301960}, issn = {1095-9203}, support = {KL2 TR001100/TR/NCATS NIH HHS/United States ; K08 CA188615/CA/NCI NIH HHS/United States ; K12 CA090628/CA/NCI NIH HHS/United States ; U24 CA224316/CA/NCI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {B7-H1 Antigen/*antagonists & inhibitors ; CTLA-4 Antigen/antagonists & inhibitors ; Carcinoma, Renal Cell/*genetics/*therapy ; Chromosomal Proteins, Non-Histone/genetics ; Cohort Studies ; Exome/genetics ; Gene Expression Profiling ; Genomics ; Humans ; Immunotherapy/*methods ; Kidney Neoplasms/*genetics/*therapy ; Mutation ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; Transcription Factors/genetics ; }, abstract = {Immune checkpoint inhibitors targeting the programmed cell death 1 receptor (PD-1) improve survival in a subset of patients with clear cell renal cell carcinoma (ccRCC). To identify genomic alterations in ccRCC that correlate with response to anti-PD-1 monotherapy, we performed whole-exome sequencing of metastatic ccRCC from 35 patients. We found that clinical benefit was associated with loss-of-function mutations in the PBRM1 gene (P = 0.012), which encodes a subunit of the PBAF switch-sucrose nonfermentable (SWI/SNF) chromatin remodeling complex. We confirmed this finding in an independent validation cohort of 63 ccRCC patients treated with PD-1 or PD-L1 (PD-1 ligand) blockade therapy alone or in combination with anti-CTLA-4 (cytotoxic T lymphocyte-associated protein 4) therapies (P = 0.0071). Gene-expression analysis of PBAF-deficient ccRCC cell lines and PBRM1-deficient tumors revealed altered transcriptional output in JAK-STAT (Janus kinase-signal transducers and activators of transcription), hypoxia, and immune signaling pathways. PBRM1 loss in ccRCC may alter global tumor-cell expression profiles to influence responsiveness to immune checkpoint therapy.}, } @article {pmid29301959, year = {2018}, author = {Plesa, C and Sidore, AM and Lubock, NB and Zhang, D and Kosuri, S}, title = {Multiplexed gene synthesis in emulsions for exploring protein functional landscapes.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {343-347}, pmid = {29301959}, issn = {1095-9203}, support = {DP2 GM114829/GM/NIGMS NIH HHS/United States ; T32 GM007185/GM/NIGMS NIH HHS/United States ; }, mesh = {Emulsions ; Escherichia coli/genetics ; Gene Knockout Techniques ; Genes, Essential ; *Genes, Synthetic ; Genetic Complementation Test ; Oligonucleotides/chemical synthesis/chemistry/genetics ; Proteins/genetics/*physiology ; Synthetic Biology/methods ; }, abstract = {Improving our ability to construct and functionally characterize DNA sequences would broadly accelerate progress in biology. Here, we introduce DropSynth, a scalable, low-cost method to build thousands of defined gene-length constructs in a pooled (multiplexed) manner. DropSynth uses a library of barcoded beads that pull down the oligonucleotides necessary for a gene's assembly, which are then processed and assembled in water-in-oil emulsions. We used DropSynth to successfully build more than 7000 synthetic genes that encode phylogenetically diverse homologs of two essential genes in Escherichia coli We tested the ability of phosphopantetheine adenylyltransferase homologs to complement a knockout E. coli strain in multiplex, revealing core functional motifs and reasons underlying homolog incompatibility. DropSynth coupled with multiplexed functional assays allows us to rationally explore sequence-function relationships at an unprecedented scale.}, } @article {pmid29301958, year = {2018}, author = {Pan, D and Kobayashi, A and Jiang, P and Ferrari de Andrade, L and Tay, RE and Luoma, AM and Tsoucas, D and Qiu, X and Lim, K and Rao, P and Long, HW and Yuan, GC and Doench, J and Brown, M and Liu, XS and Wucherpfennig, KW}, title = {A major chromatin regulator determines resistance of tumor cells to T cell-mediated killing.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6377}, pages = {770-775}, pmid = {29301958}, issn = {1095-9203}, support = {R01 CA173750/CA/NCI NIH HHS/United States ; U24 CA224316/CA/NCI NIH HHS/United States ; T32 GM074897/GM/NIGMS NIH HHS/United States ; R01 HG008927/HG/NHGRI NIH HHS/United States ; T32 CA207021/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins ; CRISPR-Associated Protein 9 ; CRISPR-Cas Systems ; Cell Line, Tumor ; Chromosomal Proteins, Non-Histone/genetics/*metabolism ; Cytotoxicity, Immunologic/*genetics ; Endonucleases ; Genetic Testing ; HMGB Proteins/genetics/metabolism ; Humans ; Immunotherapy ; Interferon-gamma/therapeutic use ; Melanoma, Experimental/genetics/*immunology/*therapy ; Mice ; Skin Neoplasms/genetics/*immunology/*therapy ; T-Lymphocytes, Cytotoxic/*immunology ; Transcription Factors/genetics/*metabolism ; }, abstract = {Many human cancers are resistant to immunotherapy, for reasons that are poorly understood. We used a genome-scale CRISPR-Cas9 screen to identify mechanisms of tumor cell resistance to killing by cytotoxic T cells, the central effectors of antitumor immunity. Inactivation of >100 genes-including Pbrm1, Arid2, and Brd7, which encode components of the PBAF form of the SWI/SNF chromatin remodeling complex-sensitized mouse B16F10 melanoma cells to killing by T cells. Loss of PBAF function increased tumor cell sensitivity to interferon-γ, resulting in enhanced secretion of chemokines that recruit effector T cells. Treatment-resistant tumors became responsive to immunotherapy when Pbrm1 was inactivated. In many human cancers, expression of PBRM1 and ARID2 inversely correlated with expression of T cell cytotoxicity genes, and Pbrm1-deficient murine melanomas were more strongly infiltrated by cytotoxic T cells.}, } @article {pmid29301957, year = {2018}, author = {Cantuti-Castelvetri, L and Fitzner, D and Bosch-Queralt, M and Weil, MT and Su, M and Sen, P and Ruhwedel, T and Mitkovski, M and Trendelenburg, G and Lütjohann, D and Möbius, W and Simons, M}, title = {Defective cholesterol clearance limits remyelination in the aged central nervous system.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {684-688}, doi = {10.1126/science.aan4183}, pmid = {29301957}, issn = {1095-9203}, support = {//European Research Council/International ; }, mesh = {Aging/metabolism/*physiology ; Animals ; Apolipoproteins E/genetics/metabolism ; Central Nervous System/metabolism/*physiology ; Cholesterol/*metabolism ; Crystallization ; Demyelinating Diseases/*metabolism ; Lysosome-Associated Membrane Glycoproteins/metabolism ; Mice ; Mice, Knockout ; Myelin Sheath/*metabolism/pathology ; Phagocytes/metabolism ; *Remyelination ; }, abstract = {Age-associated decline in regeneration capacity limits the restoration of nervous system functionality after injury. In a model for demyelination, we found that old mice fail to resolve the inflammatory response initiated after myelin damage. Aged phagocytes accumulated excessive amounts of myelin debris, which triggered cholesterol crystal formation and phagolysosomal membrane rupture and stimulated inflammasomes. Myelin debris clearance required cholesterol transporters, including apolipoprotein E. Stimulation of reverse cholesterol transport was sufficient to restore the capacity of old mice to remyelinate lesioned tissue. Thus, cholesterol-rich myelin debris can overwhelm the efflux capacity of phagocytes, resulting in a phase transition of cholesterol into crystals and thereby inducing a maladaptive immune response that impedes tissue regeneration.}, } @article {pmid29301722, year = {2018}, author = {Fouet, C and Atkinson, P and Kamdem, C}, title = {Human Interventions: Driving Forces of Mosquito Evolution.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {127-139}, doi = {10.1016/j.pt.2017.10.012}, pmid = {29301722}, issn = {1471-5007}, support = {R01 AI113248/AI/NIAID NIH HHS/United States ; }, mesh = {Africa South of the Sahara ; Animals ; *Biological Evolution ; Culicidae/*genetics ; Genome, Insect/*genetics ; Humans ; Insecticide Resistance/*genetics ; *Insecticides ; Mosquito Vectors/genetics ; }, abstract = {One of the most common strategies for controlling mosquito-borne diseases relies on the use of chemical pesticides to repel or kill the mosquito vector. Pesticide exposure interferes with several key biological functions in the mosquito and triggers a variety of adaptive responses whose underlying mechanisms are only partially elucidated. The availability of reference genome sequences opens up the possibility of tracking signatures of evolutionary changes, including the most recent, across the genomes of many vector species. In this review, we highlight the recent genomic changes, which contribute to the fascinating adaptation of malaria vectors of the sub-Saharan African region to intensive insecticide-based interventions. We emphasize the operational significance of detailed genomic knowledge for current monitoring and decision-making.}, } @article {pmid29301573, year = {2018}, author = {Shahen, M and Guo, Z and Shar, AH and Ebaid, R and Tao, Q and Zhang, W and Wu, Z and Bai, Y and Fu, Y and Zheng, C and Wang, H and Shar, PA and Liu, J and Wang, Z and Xiao, W and Wang, Y}, title = {Dengue virus causes changes of MicroRNA-genes regulatory network revealing potential targets for antiviral drugs.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {2}, pmid = {29301573}, issn = {1752-0509}, support = {31170796//Northwest A and F University (CN)/ ; 81373892//National Natural Science Foundation of China/ ; 31540008//National Natural Science Foundation of China/ ; }, abstract = {BACKGROUND: Dengue virus (DENV) is an increasing global health threat and associated with induction of both a long-lived protective immune response and immune-suppression. So far, the potency of treatment of DENV via antiviral drugs is still under investigation. Recently, increasing evidences suggest the potential role of microRNAs (miRNAs) in regulating DENV. The present study focused on the function of miRNAs in innate insusceptible reactions and organization of various types of immune cells and inflammatory responses for DENV. Three drugs were tested including antiviral herbal medicine ReDuNing (RDN), Loratadine (LRD) and Acetaminophen.

RESULTS: By the microarray expression of miRNAs in 165 Patients. Results showed that 89 active miRNAs interacted with 499 potential target genes, during antiviral treatment throughout the critical stage of DENV. Interestingly, reduction of the illness threats using RDN combined with LRD treatment showed better results than Acetaminophen alone. The inhibitions of DENV was confirmed by decrease concentrations of cytokines and interleukin parameters; like TNF-α, IFN-γ, TGF-β1, IL-4, IL-6, IL-12, and IL-17; after treatment and some coagulants factors increased.

CONCLUSIONS: This study showed a preliminary support to suggest that the herbal medicine RDN combined with LRD can reduce both susceptibility and the severity of DENV.}, } @article {pmid29301569, year = {2018}, author = {Lu, D and Tiezzi, F and Schillebeeckx, C and McNulty, NP and Schwab, C and Shull, C and Maltecca, C}, title = {Host contributes to longitudinal diversity of fecal microbiota in swine selected for lean growth.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {4}, pmid = {29301569}, issn = {2049-2618}, mesh = {Animals ; Bacteria/*classification/genetics/isolation & purification ; Breeding ; Feces/microbiology ; Female ; *Gastrointestinal Microbiome ; Male ; Phylogeny ; Quantitative Trait Loci ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; Swine ; Weaning ; }, abstract = {BACKGROUND: In pigs, gut bacteria have been shown to play important roles in nutritional, physiological, and immunological processes in the host. However, the contribution of their metagenomes or part of them, which are normally reflected by fragments of 16S rRNA-encoding genes, has yet to be fully investigated.

RESULTS: Fecal samples, collected from a population of crossbred pigs at three time points, including weaning, week 15 post weaning (hereafter "week 15"), and end-of-feeding test (hereafter "off-test"), were used to evaluate changes in the composition of the fecal microbiome of each animal over time. This study used 1205, 1295, and 1283 samples collected at weaning, week 15, and off-test, respectively. There were 1039 animals that had samples collected at all three time points and also had phenotypic records on back fat thickness (BF) and average daily body weight gain (ADG). Firmicutes and Bacteroidetes were the most abundant phyla at all three time points. The most abundant genera at all three time points included Clostridium, Escherichia, Bacteroides, Prevotella, Ruminococcus, Fusobacterium, Campylobacter, Eubacterium, and Lactobacillus. Two enterotypes were identified at each time point. However, only enterotypes at week 15 and off-test were significantly associated with BF. We report herein two novel findings: (i) alpha diversity and operational taxonomic unit (OTU) richness were moderately heritable at week 15, h2 of 0.15 ± 0.06 to 0.16 ± 0.07 and 0.23 ± 0.09 to 0.26 ± 0.08, respectively, as well as at off-test, h2 of 0.20 ± 0.09 to 0.33 ± 0.10 and 0.17 ± 0.08 to 0.24 ± 0.08, respectively, whereas very low heritability estimates for both measures were detected at weaning; and (ii) alpha diversity at week 15 had strong and negative genetic correlations with BF, - 0.53 ± 0.23 to - 0.45 ± 0.25, as well as with ADG, - 0.53 ± 0.32 to - 0.53 ± 0.29.

CONCLUSIONS: These results are important for efforts to genetically improve the domesticated pig because they suggest fecal microbiota diversity can be used as an indicator trait to improve traits that are expensive to measure.}, } @article {pmid29301510, year = {2018}, author = {Jang, SW and Kim, Y and Khan, AL and Na, CI and Lee, IJ}, title = {Exogenous short-term silicon application regulates macro-nutrients, endogenous phytohormones, and protein expression in Oryza sativa L.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {4}, pmid = {29301510}, issn = {1471-2229}, support = {716001-7//Korea Institute of Planning and Evaluation for Technology in Food, Agriculture, Forestry and Fisheries/International ; 2017R1D1A3B03030917//National Research Foundation of Korea/International ; }, mesh = {Calcium/metabolism ; Cyclopentanes/metabolism ; *Gene Expression Regulation, Plant ; Gibberellins/metabolism ; Nitrogen/metabolism ; Oryza/*drug effects/genetics/*physiology ; Oxylipins/metabolism ; Plant Growth Regulators/*metabolism/*pharmacology ; Plant Proteins/*genetics ; Salicylic Acid/metabolism ; Silicon/*pharmacology ; }, abstract = {BACKGROUND: Silicon (Si) has been known to regulate plant growth; however, the underlying mechanisms of short-term exogenous Si application on the regulation of calcium (Ca) and nitrogen (N), endogenous phytohormones, and expression of essential proteins have been little understood.

RESULTS: Exogenous Si application significantly increased Si content as compared to the control. Among Si treatments, 1.0 mM Si application showed increased phosphorus content as compared to other Si treatments (0.5, 2.0, and 4.0 mM). However, Ca accumulation was significantly reduced (1.8- to 2.0-fold) at the third-leaf stage in the control, whereas all Si treatments exhibited a dose-dependent increase in Ca as determined by radioisotope 45Ca analysis. Similarly, the radioisotope 15N for nitrogen localization and uptake showed a varying but reduced response (ranging from 1.03-10.8%) to different Si concentrations as compared to 15N application alone. Physiologically active endogenous gibberellin (GA1) was also significantly higher with exogenous Si (1.0 mM) as compared to GA20 and the control plants. A similar response was noted for endogenous jasmonic and salicylic acid synthesis in rice plants with Si application. Proteomic analysis revealed the activation of several essential proteins, such as Fe-S precursor protein, putative thioredoxin, Ser/Thr phosphatase, glucose-6-phosphate isomerase (G6P), and importin alpha-1b (Imp3), with Si application. Among the most-expressed proteins, confirmatory gene expression analysis for G6P and Imp3 showed a similar response to those of the Si treatments.

CONCLUSIONS: In conclusion, the current results suggest that short-term exogenous Si can significantly regulate rice plant physiology by influencing Ca, N, endogenous phytohormones, and proteins, and that 1.0 mM Si application is more beneficial to plants than higher concentrations.}, } @article {pmid29301494, year = {2018}, author = {Wang, Y and Feng, S and Li, S and Tang, D and Chen, Y and Chen, Y and Zhou, B}, title = {Inducement and identification of chromosome introgression and translocation of Gossypium australe on Gossypium hirsutum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {15}, pmid = {29301494}, issn = {1471-2164}, support = {2016YFD0102000//the National Key Research and Development Program of China/International ; 2013BAD01B03-04//the National Key Technology Support Program of China during the Twelfth Five-year Plan Period/International ; 31271771//the National Natural Science Foundation of China/International ; 31771845//the National Natural Science Foundation of China/International ; }, mesh = {Chromosome Aberrations ; *Chromosomes, Plant/radiation effects ; Germination/radiation effects ; Gossypium/*genetics/radiation effects ; *Translocation, Genetic ; }, abstract = {BACKGROUND: We previously reported the development of a set of Gossypium hirsutum-G. australe alien chromosome addition lines. Naturally, however, G. hirsutum-G. australe chromosome exchanges were very limited, impeding the stable transference of useful genes from G. australe (G2G2 genome) into the most cultivated cotton, G. hirsutum (AADD).

RESULTS: In the present report, the pollen from a pentaploid (2n = AADDG2) of G. hirsutum-G. australe was irradiated with seven different doses ranging from 10 to 40 Grays and used to pollinate emasculated flowers of G. hirsutum over three consecutive years. Irradiation greatly increased the genetic recombination rates of the G. hirsutum and G. australe chromosomes and a total of 107 chromosome introgression individuals in 192 GISH-negative (with no GISH signal on chromosome) survived individuals, 11 chromosome translocation individuals (containing 12 chromosome translocation events) and 67 chromosome addition individuals were obtained in 70 GISH-positive (with GISH signal(s) on chromosome(s)) survived individuals, which are invaluable for mining desirable genes from G. australe. Multicolor genomic in situ hybridization results showed that there were three types of translocation, whole arm translocation, large alien segment translocation and small alien segment translocation, and that all translocations occurred between the G2-genome and the A-subgenome chromosomes in G. hirsutum. We also found that higher doses induced much higher rates of chromosome variation but also greatly lowered the seed viability and seedling survivability.

CONCLUSIONS: Irradiation has been successfully employed to induce chromosome introgressions and chromosome translocations and promote chromosome exchanges between cultivated and wild species. In addition, by balancing the rates of chromosome introgression and translocation to those of seed set, seed germination, and seedling rates in the M1 generation, we conclude that the dosage of 20 Grays is the most suitable. The established methodology may guide the utilization of the tertiary gene pool of Gossypium species such as G. australe in cotton breeding in the future.}, } @article {pmid29301493, year = {2018}, author = {Gochez, AM and Huguet-Tapia, JC and Minsavage, GV and Shantaraj, D and Jalan, N and Strauß, A and Lahaye, T and Wang, N and Canteros, BI and Jones, JB and Potnis, N}, title = {Pacbio sequencing of copper-tolerant Xanthomonas citri reveals presence of a chimeric plasmid structure and provides insights into reassortment and shuffling of transcription activator-like effectors among X. citri strains.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {16}, pmid = {29301493}, issn = {1471-2164}, mesh = {Chromosomes, Bacterial ; Copper/pharmacology ; DNA Transposable Elements ; Genome, Bacterial ; Plasmids/*genetics ; *Recombination, Genetic ; Sequence Analysis, DNA ; Transcription Activator-Like Effectors/*genetics ; Xanthomonas/drug effects/*genetics ; }, abstract = {BACKGROUND: Xanthomonas citri, a causal agent of citrus canker, has been a well-studied model system due to recent availability of whole genome sequences of multiple strains from different geographical regions. Major limitations in our understanding of the evolution of pathogenicity factors in X. citri strains sequenced by short-read sequencing methods have been tracking plasmid reshuffling among strains due to inability to accurately assign reads to plasmids, and analyzing repeat regions among strains. X. citri harbors major pathogenicity determinants, including variable DNA-binding repeat region containing Transcription Activator-like Effectors (TALEs) on plasmids. The long-read sequencing method, PacBio, has allowed the ability to obtain complete and accurate sequences of TALEs in xanthomonads. We recently sequenced Xanthomonas citri str. Xc-03-1638-1-1, a copper tolerant A group strain isolated from grapefruit in 2003 from Argentina using PacBio RS II chemistry. We analyzed plasmid profiles, copy number and location of TALEs in complete genome sequences of X. citri strains.

RESULTS: We utilized the power of long reads obtained by PacBio sequencing to enable assembly of a complete genome sequence of strain Xc-03-1638-1-1, including sequences of two plasmids, 249 kb (plasmid harboring copper resistance genes) and 99 kb (pathogenicity plasmid containing TALEs). The pathogenicity plasmid in this strain is a hybrid plasmid containing four TALEs. Due to the intriguing nature of this pathogenicity plasmid with Tn3-like transposon association, repetitive elements and multiple putative sites for origins of replication, we might expect alternative structures of this plasmid in nature, illustrating the strong adaptive potential of X. citri strains. Analysis of the pathogenicity plasmid among completely sequenced X. citri strains, coupled with Southern hybridization of the pathogenicity plasmids, revealed clues to rearrangements of plasmids and resulting reshuffling of TALEs among strains.

CONCLUSIONS: We demonstrate in this study the importance of long-read sequencing for obtaining intact sequences of TALEs and plasmids, as well as for identifying rearrangement events including plasmid reshuffling. Rearrangement events, such as the hybrid plasmid in this case, could be a frequent phenomenon in the evolution of X. citri strains, although so far it is undetected due to the inability to obtain complete plasmid sequences with short-read sequencing methods.}, } @article {pmid29301490, year = {2018}, author = {Strader, ME and Aglyamova, GV and Matz, MV}, title = {Molecular characterization of larval development from fertilization to metamorphosis in a reef-building coral.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {17}, pmid = {29301490}, issn = {1471-2164}, support = {DEB-1501463//National Science Foundation/International ; }, mesh = {Animals ; Anthozoa/anatomy & histology/embryology/*genetics/*growth & development ; Behavior, Animal/drug effects ; Fertilization ; Larva/genetics/growth & development/metabolism ; Luminescent Proteins/metabolism ; Metamorphosis, Biological/genetics ; Transcriptome ; }, abstract = {BACKGROUND: Molecular mechanisms underlying coral larval competence, the ability of larvae to respond to settlement cues, determine their dispersal potential and are potential targets of natural selection. Here, we profiled competence, fluorescence and genome-wide gene expression in embryos and larvae of the reef-building coral Acropora millepora daily throughout 12 days post-fertilization.

RESULTS: Gene expression associated with competence was positively correlated with transcriptomic response to the natural settlement cue, confirming that mature coral larvae are "primed" for settlement. Rise of competence through development was accompanied by up-regulation of sensory and signal transduction genes such as ion channels, genes involved in neuropeptide signaling, and G-protein coupled receptor (GPCRs). A drug screen targeting components of GPCR signaling pathways confirmed a role in larval settlement behavior and metamorphosis.

CONCLUSIONS: These results gives insight into the molecular complexity underlying these transitions and reveals receptors and pathways that, if altered by changing environments, could affect dispersal capabilities of reef-building corals. In addition, this dataset provides a toolkit for asking broad questions about sensory capacity in multicellular animals and the evolution of development.}, } @article {pmid29301488, year = {2018}, author = {Sun, Y and Hou, H and Song, H and Lin, K and Zhang, Z and Hu, J and Pang, E}, title = {The comparison of alternative splicing among the multiple tissues in cucumber.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {5}, pmid = {29301488}, issn = {1471-2229}, support = {31571361//the National Natural Science Foundation of China/International ; 31421063//the National Natural Science Foundation of China/International ; }, mesh = {*Alternative Splicing ; Cucumis sativus/*genetics/metabolism ; Gene Expression Profiling ; *Transcriptome ; }, abstract = {BACKGROUND: Alternative splicing (AS) is an important post-transcriptional process. It has been suggested that most AS events are subject to tissue-specific regulation. However, the global dynamics of AS in different tissues are poorly explored.

RESULTS: To analyse global changes in AS in multiple tissues, we identified the AS events and constructed a comprehensive catalogue of AS events within each tissue based on the genome-wide RNA-seq reads from ten tissues in cucumber. First, we found that 58% of the multi-exon genes underwent AS. We further obtained 565 genes with significantly more AS events compared with random genes. These genes were found significant enrichment in biological processes related to the regulation of actin filament length. Second, significantly different AS event profiles among ten tissues were found. The tissues with the same origin of development are more likely to have a relatively similar AS profile. Moreover, 7370 genes showed tissue-specific AS events and were highly enriched in biological processes related to the positive regulation of cellular component organization. Root-specificity AS genes were related to the cellular response to DNA damage stimulus. Third, the genes with different intron retention (IR) patterns among the ten tissues showed significant difference in GC percentages of the retained intron, and the number of exons and FPKM of the major transcripts.

CONCLUSIONS: Our study provided a comprehensive view of AS in multiple tissues. We revealed novel insights into the patterns of AS in multiple tissues and the tissue-specific AS in cucumber.}, } @article {pmid29301485, year = {2018}, author = {Deshpande, A and Lang, W and McDowell, T and Sivakumar, S and Zhang, J and Wang, J and San Lucas, FA and Fowler, J and Kadara, H and Scheet, P}, title = {Strategies for identification of somatic variants using the Ion Torrent deep targeted sequencing platform.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {5}, pmid = {29301485}, issn = {1471-2105}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; P30CA016677/CA/NCI NIH HHS/United States ; R01HG005859/CA/NCI NIH HHS/United States ; R01 HG005859/HG/NHGRI NIH HHS/United States ; R01 CA205608/CA/NCI NIH HHS/United States ; RP150079//Cancer Prevention and Research Institute of Texas (US)/International ; }, mesh = {Carcinoma, Non-Small-Cell Lung/genetics/pathology ; High-Throughput Nucleotide Sequencing/*methods ; Humans ; Lung Neoplasms/genetics/pathology ; Mutation ; Sequence Analysis, DNA ; Software ; }, abstract = {BACKGROUND: 'Next-generation' (NGS) sequencing has wide application in medical genetics, including the detection of somatic variation in cancer. The Ion Torrent-based (IONT) platform is among NGS technologies employed in clinical, research and diagnostic settings. However, identifying mutations from IONT deep sequencing with high confidence has remained a challenge. We compared various computational variant-calling methods to derive a variant identification pipeline that may improve the molecular diagnostic and research utility of IONT.

RESULTS: Using IONT, we surveyed variants from the 409-gene Comprehensive Cancer Panel in whole-section tumors, intra-tumoral biopsies and matched normal samples obtained from frozen tissues and blood from four early-stage non-small cell lung cancer (NSCLC) patients. We used MuTect, Varscan2, IONT's proprietary Ion Reporter, and a simple subtraction we called "Poor Man's Caller." Together these produced calls at 637 loci across all samples. Visual validation of 434 called variants was performed, and performance of the methods assessed individually and in combination. Of the subset of inspected putative variant calls (n=223) in genomic regions that were not intronic or intergenic, 68 variants (30%) were deemed valid after visual inspection. Among the individual methods, the Ion Reporter method offered perhaps the most reasonable tradeoffs. Ion Reporter captured 83% of all discovered variants; 50% of its variants were visually validated. Aggregating results from multiple packages offered varied improvements in performance.

CONCLUSIONS: Overall, Ion Reporter offered the most attractive performance among the individual callers. This study suggests combined strategies to maximize sensitivity and positive predictive value in variant calling using IONT deep sequencing.}, } @article {pmid29301006, year = {2018}, author = {Weaver, S and Shank, SD and Spielman, SJ and Li, M and Muse, SV and Kosakovsky Pond, SL}, title = {Datamonkey 2.0: a modern web application for characterizing selective and other evolutionary processes.}, journal = {Molecular biology and evolution}, volume = {}, number = {}, pages = {}, pmid = {29301006}, issn = {1537-1719}, support = {R01 GM093939/GM/NIGMS NIH HHS/United States ; U01 GM110749/GM/NIGMS NIH HHS/United States ; }, abstract = {Inference of how evolutionary forces have shaped extant genetic diversity is a cornerstone of modern comparative sequence analysis. Advances in sequence generation and increased statistical sophistication of relevant methods now allow researchers to extract ever more evolutionary signal from the data, albeit at an increased computational cost. Here, we announce the release of Datamonkey 2.0, a completely re-engineered version of the Datamonkey web-server for analyzing evolutionary signatures in sequence data. For this endeavor, we leveraged recent developments in open-source libraries that facilitate interactive, robust, and scalable web application development. Datamonkey 2.0 provides a carefully curated collection of methods for interrogating coding-sequence alignments for imprints of natural selection, packaged as a responsive (i.e. can be viewed on tablet and mobile devices), fully interactive, and API-enabled web application. To complement Datamonkey 2.0, we additionally release HyPhy Vision, an accompanying JavaScript application for visualizing analysis results. HyPhy Vision can also be used separately from Datamonkey 2.0 to visualize locally-executed HyPhy analyses. Together, Datamonkey 2.0 and HyPhy Vision showcase how scientific software development can benefit from general-purpose open-source frameworks. Datamonkey 2.0 is freely and publicly available at http://www.datamonkey. org, and the underlying codebase is available from https://github.com/veg/datamonkey-js.}, } @article {pmid29301001, year = {2018}, author = {Pugach, I and Duggan, AT and Merriwether, DA and Friedlaender, FR and Friedlaender, JS and Stoneking, M}, title = {The Gateway from Near into Remote Oceania: New Insights from Genome-Wide Data.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {871-886}, pmid = {29301001}, issn = {1537-1719}, abstract = {A widely accepted two-wave scenario of human settlement of Oceania involves the first out-of-Africa migration circa 50,000 years ago (ya), and the more recent Austronesian expansion, which reached the Bismarck Archipelago by 3,450 ya. Whereas earlier genetic studies provided evidence for extensive sex-biased admixture between the incoming and the indigenous populations, some archaeological, linguistic, and genetic evidence indicates a more complicated picture of settlement. To study regional variation in Oceania in more detail, we have compiled a genome-wide data set of 823 individuals from 72 populations (including 50 populations from Oceania) and over 620,000 autosomal single nucleotide polymorphisms (SNPs). We show that the initial dispersal of people from the Bismarck Archipelago into Remote Oceania occurred in a "leapfrog" fashion, completely by-passing the main chain of the Solomon Islands, and that the colonization of the Solomon Islands proceeded in a bidirectional manner. Our results also support a divergence between western and eastern Solomons, in agreement with the sharp linguistic divide known as the Tryon-Hackman line. We also report substantial post-Austronesian gene flow across the Solomons. In particular, Santa Cruz (in Remote Oceania) exhibits extraordinarily high levels of Papuan ancestry that cannot be explained by a simple bottleneck/founder event scenario. Finally, we use simulations to show that discrepancies between different methods for dating admixture likely reflect different sensitivities of the methods to multiple admixture events from the same (or similar) sources. Overall, this study points to the importance of fine-scale sampling to understand the complexities of human population history.}, } @article {pmid29300951, year = {2018}, author = {Bulgheresi, S}, title = {All the microbiology nematodes can teach us.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix170}, pmid = {29300951}, issn = {1574-6941}, } @article {pmid29300936, year = {2018}, author = {Martini, MC and Quiroga, MP and Pistorio, M and Lagares, A and Centrón, D and Del Papa, MF}, title = {Novel environmental class 1 integrons and cassette arrays recovered from an on-farm bio-purification plant.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fix190}, pmid = {29300936}, issn = {1574-6941}, abstract = {Rapid dissemination and emergence of novel antibiotic resistance genes among bacteria are rising problems worldwide. Since their discovery in clinical isolates in the late 1980s, class 1 integrons have been found in a wide range of bacterial genera and have been extensively studied as contributors to dissemination of antibiotic resistance. The present study aimed to investigate the presence and structure of class 1 integrons in plasmid-carrying bacterial isolates obtained from a biopurification system used for decontamination of pesticide-contaminated water as well as their possible role as reservoir of antimicrobial resistance gene cassettes. A total of 35 representative isolates were screened for the presence of class 1 integron integrase encoded by intI1. PCR and DNA sequencing revealed the presence of six class 1 integrons with four variable regions: 5΄CS-aadA1b-3΄CS, 5΄CS-aadA2-3΄CS, 5΄CS-aadA11cΔ-3΄CS and 5΄CS-dfrB3-aadA1di-catB2-aadA6k-3΄CS, the last two being unseen arrays of antimicrobial resistance gene cassettes associated with novel environmental alleles of intI1. These four class 1 integrons were identified as being present in four different genera, including Ochrobactrum, and Variovorax, where class 1 integrons have not been previously reported. The results provide evidence of the biopurification systems as a tank of class 1 integron carrying strains and novel environmental class 1 integron integrases associated with antimicrobial resistance gene cassette arrays.}, } @article {pmid29300934, year = {2018}, author = {Li, AD and Metch, JW and Wang, Y and Garner, E and Zhang, AN and Riquelme, MV and Vikesland, PJ and Pruden, A and Zhang, T}, title = {Effects of sample preservation and DNA extraction on enumeration of antibiotic resistance genes in wastewater.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix189}, pmid = {29300934}, issn = {1574-6941}, abstract = {With the growing application of high-throughput sequencing-based metagenomics for profiling antibiotic resistance genes (ARGs) in wastewater treatment plants (WWTPs), comparison of sample pretreatment and DNA extraction methods are needed to move toward standardized comparisons among laboratories. Three widely employed DNA extraction methods (FastDNA® Spin Kit for Soil, PowerSoil® DNA Isolation Kit and ZR Fecal DNA MiniPrep), with and without preservation in 50% ethanol and freezing, were applied to the influent, activated sludge and effluent of two WWTPs, in Hong Kong and in the USA. Annotated sequences obtained from the DNA extracted using the three kits shared similar taxonomy and ARG profiles. Overall, it was found that the DNA yield and purity, and diversity of ARGs captured were all highest when applying the FastDNA SPIN Kit for Soil for all three WWTP sample types investigated here (influent, activated sludge, effluent). Quantitative polymerase chain reaction of 16S rRNA genes confirmed the same trend as DNA extraction yields and similar recovery of a representative Gram-negative bacterium (Escherichia coli). Moreover, sample fixation in ethanol, deep-freezing and overseas shipment had no discernable effect on ARG profiles, as compared to fresh samples. This approach serves to inform future efforts toward global comparisons of ARG distributions in WWTPs.}, } @article {pmid29300161, year = {2018}, author = {Jeon, J and Ten, LN and Lee, JJ and Lee, SY and Park, S and Cho, YJ and Kim, MK and Jung, HY}, title = {Larkinella knui sp. nov., isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {582-588}, doi = {10.1099/ijsem.0.002550}, pmid = {29300161}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, motile by gliding, rod-shaped, aerobic bacterium, designated 15J6-3T6T, was isolated from a soil sample collected from Jeju Island, South Korea, and characterized taxonomically using a polyphasic approach. Comparative 16S rRNA gene sequence analysis showed that strain 15J6-3T6T belongs to the family Cytophagaceae and is related to Larkinella harenae 15J9-9T (93.9 % similarity), Larkinella arboricola Z0532T (93.6 %), Larkinella bovis M2TB15T (93.3 %), and Larkinella insperata LMG 22510T (93.3 %). The DNA G+C content of strain 15J6-3T6T was 50.6 mol%. The detection of phosphatidylethanolamine and an unidentified polar lipid as major polar lipids, menaquinone-7 as the predominant quinone, and C16 : 1ω5c, iso-C15 : 0, and iso-C17 : 0 3-OH as the major fatty acids also supports the affiliation of the isolate to the genus Larkinella. Based on its phenotypic properties and phylogenetic distinctiveness, we propose that strain 15J6-3T6T should be classified in the genus Larkinella as a representative of a novel species, for which the name Larkinella knui sp. nov. is proposed. The type strain is 15J6-3T6T (=KCTC 42998T=JCM 31989T).}, } @article {pmid29300160, year = {2018}, author = {Gan, L and Zhang, H and Tian, J and Li, X and Long, X and Zhang, Y and Dai, Y and Tian, Y}, title = {Planococcus salinus sp. nov., a moderately halophilic bacterium isolated from a saline-alkali soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {589-595}, doi = {10.1099/ijsem.0.002548}, pmid = {29300160}, issn = {1466-5034}, mesh = {Alkalies ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Planococcus Bacteria/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Salinity ; Sequence Analysis, DNA ; Soil/chemistry ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel aerobic, Gram-stain-positive, motile, moderately halophilic and coccoid bacterial strain, designated LCB217T, was isolated from a saline-alkali soil in north-western China and identified using a polyphasic taxonomic approach. Growth occurred with 3-15 % (w/v) NaCl (optimum 3-5 %), at 10-45 °C (optimum 30 °C) and at pH 7.0-9.0 (optimum pH 9.0). Strain LCB217T contained MK-7 and MK-8 as the predominant menaquinones and anteiso-C15 : 0, iso-C14 : 0 and iso-C16 : 0 as the major fatty acids. The polar lipids from strain LCB217T consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylcholine, one unidentified phospholipid, one unidentified aminophospholipid and one unidentified lipid. The peptidoglycan type was A4α (l-Lys-d-Glu). Phylogenetic analysis of the 16S rRNA gene sequence showed that strain LCB217T belonged to the genus Planococcus and was closely related to the type strains Planococcus plakortidis AS/ASP6 (II)T (98.2 % similarity), Planococcus maitriensis S1T (97.7 %) and Planococcus salinarum ISL-16T (97.2 %). The G+C content of the genomic DNA was 49.4 mol%. DNA-DNA relatedness values between strain LCB217T andPlanococcusplakortidis AS/ASP6 (II)T, Planococcusmaitriensis S1T andPlanococcussalinarum ISL-16T were 29.5, 38.1 and 39.5 %, respectively. On the basis of the phenotypic, phylogenetic and genomic data, strain LCB217T represents a novel species of the genus Planococcus, for which the name Planococcus salinus sp. nov. is proposed. The type strain is LCB217T (=CGMCC 1.15685T=KCTC 33861T).}, } @article {pmid29300157, year = {2018}, author = {Yuki, M and Sakamoto, M and Nishimura, Y and Ohkuma, M}, title = {Lactococcus reticulitermitis sp. nov., isolated from the gut of the subterranean termite Reticulitermes speratus.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {596-601}, doi = {10.1099/ijsem.0.002549}, pmid = {29300157}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gastrointestinal Tract/*microbiology ; Isoptera/*microbiology ; Lactococcus/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Strain Rs-Y01T was isolated from the gut of the wood-feeding subterranean termite Reticulitermes speratus. Phylogenetic analysis based on 16S rRNA gene sequence indicated that the strain Rs-Y01T belonged to the genus Lactococcus and was most closely related to Lactococcus raffinolactis JCM 5706T with 98.1 % similarity in the 16S rRNA gene, followed by Lactococcus piscium JCM 16647T (97.2 %). Genomic comparisons of strain Rs-Y01T with L. raffinolactis JCM 5706Twere made using the Genome-to-Genome Distance Calculator and average nucleotide identity analysis (values indicated 29.2 and 84.6 %, respectively). Strain Rs-Y01T was a Gram-stain-positive, facultatively anaerobic, non-motile coco-bacilli and formed l-lactic acid. The sugar fermentation and enzyme reactions of strain Rs-Y01T differed from those of other species of the genus Lactococcus. The major cellular fatty acids were summed feature 8 (C18 : 1ω7c/C18 : 1ω6c; 32.0 %), C16 : 0 (29.7 %) and C14 : 0 (18.1 %). Based on these characteristics, strain Rs-Y01T represents a novel species of the genus Lactococcus, for which the name Lactococcusreticulitermitis sp. nov. is proposed. The type strain is Rs-Y01T (=JCM 32106T=DSM 105715T).}, } @article {pmid29300153, year = {2018}, author = {Modesto, M and Michelini, S and Oki, K and Biavati, B and Watanabe, K and Mattarelli, P}, title = {Bifidobacterium catulorum sp. nov., a novel taxon from the faeces of the baby common marmoset (Callithrix jacchus).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {575-581}, doi = {10.1099/ijsem.0.002545}, pmid = {29300153}, issn = {1466-5034}, mesh = {Aldehyde-Lyases/genetics ; Animals ; Bacterial Typing Techniques ; Base Composition ; Bifidobacterium/*classification/genetics/isolation & purification ; Callithrix/*microbiology ; Chaperonin 60/genetics ; DNA, Bacterial/genetics ; Feces/microbiology ; Genes, Bacterial ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {In our previous study based on hsp60 PCR-restriction fragment length polymorphism and 16S rRNA gene sequencing, we stated that the bifidobacterial strains isolated from the individual faecal samples of five baby common marmosets constituted different phylogenetically isolated groups of the genus Bifidobacterium. In that study, we also proposed that these isolated groups potentially represented novel species of the genus Bifidobacterium. Out of them, Bifidobacterium aesculapii, Bifidobacterium myosotis, Bifidobacterium tissieri and Bifidobacterium hapali, have been described recently. Another strain, designated MRM 8.19T, has been classified as member of the genus Bifidobacterium on the basis of positive results for fructose-6-phosphate phosphoketolase activity and analysis of partial 16S rRNA, hsp60, clpC, dnaJ, dnaG and rpoB gene sequences. Analysis of 16S rRNA and hsp60 gene sequences revealed that strain MRM 8.19T was related to B. tissieri DSM 100201T (95.8 %) and to Bifidobacterium bifidum ATCC 29521T (93.7 %), respectively. The DNA G+C composition was 63.7 mol% and the peptidoglycan structure was l-Orn(Lys)-l-Ser. Based on the phylogenetic, genotypic and phenotypic data reported, strain MRM 8.19T represents a novel taxon within the genus Bifidobacterium for which the name Bifidobacterium catulorum sp. nov. (type strain MRM 8.19T=DSM 103154T=JCM 31794T) is proposed.}, } @article {pmid29300151, year = {2018}, author = {Niu, L and Xiong, M and Zhang, J and Xiang, Y and Song, L and Hua, Z and Li, W}, title = {Bacillus camelliae sp. nov., isolated from Pu'er tea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {564-569}, doi = {10.1099/ijsem.0.002542}, pmid = {29300151}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; *Food Microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Tea/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel aerobic, Gram-stain-positive, sporogenous, rod-shaped bacterial strain, 7578-1T, was isolated from ripened Pu'er tea. Based on 16S rRNA gene sequence similarity comparisons, strain 7578-1T was grouped into the genus Bacillus and appeared to be closely related to the type strains Bacillus shackletoniiLMG 18435T (98.4 %), Bacillus acidicolaDSM 14745T (97.6 %), Bacillus paralicheniformis KACC 18426T (97.2 %) and Bacillus ginsengihumi KCTC 13944T (96.7 %). The fatty acid profile containing the major fatty acids, iso-C15 : 0, anteiso-C15 : 0 and anteiso-C17 : 0 supported the allocation of strain 7578-1T to the genus Bacillus. The strain had a cell-wall type A1γ peptidoglycan with meso-diaminopimelic acid as the diagnostic diamino acid. The major menaquinone was MK-7 (95 %). The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, one unidentified phospholipid and one unidentified lipid. The average nucleotide identity values between strain 7578-1T and its most closely related species were 67.8-82.4 % by OrthoANIu analysis. The DNA-DNA relatedness value between strain 7578-1T and the type strains of closely related species were 17-39 %, again indicating that strain 7578-1T represented a novel species in the genus Bacillus. The DNA G+C content of strain 7578-1T was 36.0 mol%. On the basis of the presented polyphasic evidence, strain 7578-1T is considered to represent a novel species of the genus Bacillus, for which we propose the name Bacillus camelliae sp. nov. The type strain is 7578-1T (=CGMCC 1.15374T=KCTC 33845T).}, } @article {pmid29300044, year = {2018}, author = {Silk, J}, title = {Put telescopes on the far side of the Moon.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {6}, doi = {10.1038/d41586-017-08941-8}, pmid = {29300044}, issn = {1476-4687}, mesh = {Astronauts ; Europe ; Microwaves ; *Moon ; Radio Waves ; Space Flight/*instrumentation ; Spacecraft/instrumentation ; *Telescopes ; United States ; United States National Aeronautics and Space Administration ; }, } @article {pmid29300043, year = {2018}, author = {}, title = {A bag of surprises.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {27}, doi = {10.1038/d41586-018-00003-x}, pmid = {29300043}, issn = {1476-4687}, } @article {pmid29300042, year = {2018}, author = {Medema, JP}, title = {Escape from senescence boosts tumour growth.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {37-38}, doi = {10.1038/d41586-017-08652-0}, pmid = {29300042}, issn = {1476-4687}, mesh = {*Cellular Senescence ; Humans ; *Neoplasms ; }, } @article {pmid29300041, year = {2018}, author = {}, title = {Medical research often ignores differing health outcomes for men and women.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {119}, doi = {10.1038/d41586-017-08993-w}, pmid = {29300041}, issn = {1476-4687}, mesh = {*Authorship ; Biomedical Research/*methods ; Female ; Humans ; Male ; Research Personnel/*statistics & numerical data ; *Sex Characteristics ; Sex Factors ; Treatment Outcome ; *Women's Health ; }, } @article {pmid29300040, year = {2018}, author = {Gibney, E}, title = {What to expect in 2018: science in the new year.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {12-13}, doi = {10.1038/d41586-018-00009-5}, pmid = {29300040}, issn = {1476-4687}, mesh = {Astronauts ; Astronomy/trends ; Climate Change ; Clinical Trials as Topic ; DNA, Ancient ; Drug Resistance, Microbial ; European Union/organization & administration ; Gene Editing/trends ; Genomics/trends ; Human Migration ; Humans ; Indians, North American/genetics ; Induced Pluripotent Stem Cells/transplantation ; Moon ; Neoplasms/genetics ; Open Access Publishing/trends ; Parkinson Disease/pathology/therapy ; Phage Therapy/trends ; Physics ; Politics ; Science/*trends ; Space Flight/trends ; Synchrotrons ; }, } @article {pmid29300039, year = {2018}, author = {Reardon, S}, title = {US government lifts ban on risky pathogen research.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {11}, doi = {10.1038/d41586-017-08837-7}, pmid = {29300039}, issn = {1476-4687}, mesh = {*Censorship, Research ; Containment of Biohazards/methods ; Dual Use Research/*legislation & jurisprudence ; Epidemiological Monitoring ; Financing, Organized/*legislation & jurisprudence ; *Gain of Function Mutation ; Humans ; Middle East Respiratory Syndrome Coronavirus/genetics/pathogenicity ; National Institutes of Health (U.S.)/economics/*legislation & jurisprudence ; Orthomyxoviridae/genetics/pathogenicity ; Pandemics/prevention & control ; Research Support as Topic/legislation & jurisprudence ; Risk Assessment/methods ; SARS Virus/genetics/pathogenicity ; Uncertainty ; United States ; Viral Vaccines ; Viruses/*genetics/immunology/*pathogenicity ; }, } @article {pmid29300038, year = {2018}, author = {}, title = {Ben Barres, NASA missions and compulsory vaccines.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {7}, doi = {10.1038/d41586-017-08944-5}, pmid = {29300038}, issn = {1476-4687}, } @article {pmid29300037, year = {2018}, author = {Stanley, RHR}, title = {Ocean thermometer from the past.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {30-31}, doi = {10.1038/d41586-017-08721-4}, pmid = {29300037}, issn = {1476-4687}, } @article {pmid29300036, year = {2018}, author = {Maxmen, A}, title = {A reboot for chronic fatigue syndrome research.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {14-17}, doi = {10.1038/d41586-017-08965-0}, pmid = {29300036}, issn = {1476-4687}, mesh = {Adult ; Biomedical Research/economics/*trends ; Exercise ; Fatigue Syndrome, Chronic/*etiology/metabolism/psychology/*therapy ; Female ; Humans ; Male ; Microbiota ; Suicide ; Xenotropic murine leukemia virus-related virus/pathogenicity ; }, } @article {pmid29300035, year = {2018}, author = {}, title = {Need a paper? Get a plug-in.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {116}, doi = {10.1038/d41586-017-08995-8}, pmid = {29300035}, issn = {1476-4687}, } @article {pmid29300034, year = {2018}, author = {Kulmala, M}, title = {Build a global Earth observatory.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {21-23}, doi = {10.1038/d41586-017-08967-y}, pmid = {29300034}, issn = {1476-4687}, mesh = {Atmosphere/*chemistry ; Cities ; Cost-Benefit Analysis ; *Earth (Planet) ; *Ecosystem ; Environmental Monitoring/economics/*instrumentation/*methods ; *International Cooperation ; Remote Sensing Technology/economics/instrumentation/methods ; Satellite Imagery/economics/instrumentation ; South America ; }, } @article {pmid29300033, year = {2018}, author = {Vivian, C and Williamson, P and Boyd, P}, title = {Climate engineering is not just about the atmosphere.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {27}, doi = {10.1038/d41586-017-09009-3}, pmid = {29300033}, issn = {1476-4687}, mesh = {*Atmosphere ; Carbon Dioxide ; *Climate ; Engineering ; }, } @article {pmid29300032, year = {2018}, author = {}, title = {US universities to provide tools for post-PhD life.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {119}, doi = {10.1038/d41586-017-08991-y}, pmid = {29300032}, issn = {1476-4687}, } @article {pmid29300031, year = {2018}, author = {Albertin, CB and Ragsdale, CW}, title = {More than one way to a central nervous system.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {34-36}, doi = {10.1038/d41586-017-08195-4}, pmid = {29300031}, issn = {1476-4687}, mesh = {*Central Nervous System ; Humans ; }, } @article {pmid29300030, year = {2018}, author = {Zhao, W and Xiong, Q}, title = {Nanoscale interfaces made easily.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {32-34}, doi = {10.1038/d41586-017-08755-8}, pmid = {29300030}, issn = {1476-4687}, mesh = {*Nanostructures ; }, } @article {pmid29300028, year = {2018}, author = {Bargmann, C}, title = {How the Chan Zuckerberg Science Initiative plans to solve disease by 2100.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {19-21}, doi = {10.1038/d41586-017-08966-z}, pmid = {29300028}, issn = {1476-4687}, } @article {pmid29300027, year = {2018}, author = {}, title = {'Gourmet investigator' and 'Super catalysts'.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {119}, doi = {10.1038/d41586-018-00001-z}, pmid = {29300027}, issn = {1476-4687}, } @article {pmid29300026, year = {2018}, author = {Rumpel, C and Lehmann, J and Chabbi, A}, title = {'4 per 1,000' initiative will boost soil carbon for climate and food security.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {27}, doi = {10.1038/d41586-017-09010-w}, pmid = {29300026}, issn = {1476-4687}, mesh = {Agriculture/*methods/trends ; Carbon/*analysis ; *Carbon Sequestration ; Congresses as Topic ; *Conservation of Natural Resources/trends ; *Food Supply/methods ; France ; Global Warming/prevention & control ; Goals ; Humans ; Soil/*chemistry ; }, } @article {pmid29300024, year = {2018}, author = {Brierley, A}, title = {Poaching Lake Victoria's fish for traditional Chinese medicine.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {27}, doi = {10.1038/d41586-017-09011-9}, pmid = {29300024}, issn = {1476-4687}, mesh = {Animals ; Fishes ; *Lakes ; *Medicine, Chinese Traditional ; }, } @article {pmid29300023, year = {2018}, author = {Maxmen, A}, title = {Deep learning sharpens views of cells and genes.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {9-10}, doi = {10.1038/d41586-018-00004-w}, pmid = {29300023}, issn = {1476-4687}, mesh = {Gene Expression Profiling ; Humans ; Image Processing, Computer-Assisted/*methods ; *Machine Learning ; Myocardial Infarction/diagnosis/pathology ; Neoplasms/diagnosis/pathology ; *Neural Networks (Computer) ; Retina/anatomy & histology/pathology ; }, } @article {pmid29300022, year = {2018}, author = {Kwok, R}, title = {Put it on camera: How to get into scientific film- and video-making.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {117-119}, doi = {10.1038/d41586-017-08862-6}, pmid = {29300022}, issn = {1476-4687}, mesh = {Aquatic Organisms ; Job Satisfaction ; *Motion Pictures/statistics & numerical data/supply & distribution ; *Research Personnel ; *Science/education ; Social Media/statistics & numerical data/supply & distribution ; *Video Recording/instrumentation/methods/statistics & numerical data/supply & distribution ; }, } @article {pmid29300020, year = {2018}, author = {Callaway, E}, title = {Facebook billionaire pours funds into high-risk research.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {10-11}, doi = {10.1038/d41586-017-08795-0}, pmid = {29300020}, issn = {1476-4687}, mesh = {Animal Welfare/economics ; Animals ; Cancer Vaccines/immunology ; Clinical Trials as Topic/economics ; Dog Diseases/immunology/prevention & control ; Dogs ; Entrepreneurship/economics ; Foundations/economics ; Fund Raising/*economics ; Gene Drive Technology ; Global Health/economics ; Humans ; Malaria/prevention & control/transmission ; Neoplasms/immunology/prevention & control/veterinary ; Research/*economics ; Research Support as Topic/*economics ; *Risk-Taking ; San Francisco ; }, } @article {pmid29300019, year = {2018}, author = {Nave, KA and Ehrenreich, H}, title = {A bloody brake on myelin repair.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {31-32}, doi = {10.1038/d41586-017-08232-2}, pmid = {29300019}, issn = {1476-4687}, mesh = {*Fibrinogen ; Humans ; *Myelin Sheath ; Oligodendroglioma ; Signal Transduction ; }, } @article {pmid29300018, year = {2018}, author = {}, title = {Reward research that changes society.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {5}, doi = {10.1038/d41586-017-08943-6}, pmid = {29300018}, issn = {1476-4687}, mesh = {Databases, Factual ; Humans ; Periodicals as Topic/*trends ; *Research/economics/standards ; Research Support as Topic/*trends ; *Reward ; *Social Change ; Water Quality ; }, } @article {pmid29300017, year = {2018}, author = {Solé, R and Conde-Pueyo, N}, title = {Ultrasound approach tracks gut microbes.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {36-37}, doi = {10.1038/d41586-017-08911-0}, pmid = {29300017}, issn = {1476-4687}, mesh = {*Gastrointestinal Tract ; Humans ; *Ultrasonography ; }, } @article {pmid29300016, year = {2018}, author = {Stock, G}, title = {Brexit must protect UK-EU research collaborations.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {27}, doi = {10.1038/d41586-017-09005-7}, pmid = {29300016}, issn = {1476-4687}, mesh = {*European Union ; Politics ; *Research ; United Kingdom ; }, } @article {pmid29300015, year = {2018}, author = {Nowogrodzki, A}, title = {The research hardware in your video-game system.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {115-116}, doi = {10.1038/d41586-017-08968-x}, pmid = {29300015}, issn = {1476-4687}, mesh = {Accidental Falls ; Aged ; Algorithms ; Animals ; *Computers ; Dinosaurs/anatomy & histology ; Gait ; Geology/instrumentation ; Humans ; Ice Cover/chemistry ; Imaging, Three-Dimensional/instrumentation ; Paleontology/instrumentation ; Research/*instrumentation ; Robotics/instrumentation ; *Software ; *Video Games ; }, } @article {pmid29300014, year = {2018}, author = {Shahid, S and Kim, G and Johnson, NR and Wafula, E and Wang, F and Coruh, C and Bernal-Galeano, V and Phifer, T and dePamphilis, CW and Westwood, JH and Axtell, MJ}, title = {MicroRNAs from the parasitic plant Cuscuta campestris target host messenger RNAs.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {82-85}, pmid = {29300014}, issn = {1476-4687}, mesh = {Arabidopsis/*genetics/parasitology ; Base Sequence ; Cuscuta/*genetics/growth & development ; Gene Expression Regulation, Plant ; Host Specificity ; Host-Parasite Interactions/*genetics ; MicroRNAs/genetics/*metabolism ; Mutation ; *RNA Cleavage ; RNA, Messenger/genetics/*metabolism ; RNA, Plant/genetics/*metabolism ; RNA, Small Interfering/biosynthesis/genetics/metabolism ; Tobacco/*genetics/parasitology ; Virulence Factors/genetics/metabolism ; }, abstract = {Dodders (Cuscuta spp.) are obligate parasitic plants that obtain water and nutrients from the stems of host plants via specialized feeding structures called haustoria. Dodder haustoria facilitate bidirectional movement of viruses, proteins and mRNAs between host and parasite, but the functional effects of these movements are not known. Here we show that Cuscuta campestris haustoria accumulate high levels of many novel microRNAs (miRNAs) while parasitizing Arabidopsis thaliana. Many of these miRNAs are 22 nucleotides in length. Plant miRNAs of this length are uncommon, and are associated with amplification of target silencing through secondary short interfering RNA (siRNA) production. Several A. thaliana mRNAs are targeted by 22-nucleotide C. campestris miRNAs during parasitism, resulting in mRNA cleavage, secondary siRNA production, and decreased mRNA accumulation. Hosts with mutations in two of the loci that encode target mRNAs supported significantly higher growth of C. campestris. The same miRNAs that are expressed and active when C. campestris parasitizes A. thaliana are also expressed and active when it infects Nicotiana benthamiana. Homologues of target mRNAs from many other plant species also contain the predicted target sites for the induced C. campestris miRNAs. These data show that C. campestris miRNAs act as trans-species regulators of host-gene expression, and suggest that they may act as virulence factors during parasitism.}, } @article {pmid29300013, year = {2018}, author = {Zhang, H and Qiao, A and Yang, L and Van Eps, N and Frederiksen, KS and Yang, D and Dai, A and Cai, X and Zhang, H and Yi, C and Cao, C and He, L and Yang, H and Lau, J and Ernst, OP and Hanson, MA and Stevens, RC and Wang, MW and Reedtz-Runge, S and Jiang, H and Zhao, Q and Wu, B}, title = {Structure of the glucagon receptor in complex with a glucagon analogue.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {106-110}, pmid = {29300013}, issn = {1476-4687}, mesh = {Crystallography, X-Ray ; Drug Partial Agonism ; Glucagon/*analogs & derivatives ; Humans ; Ligands ; Models, Molecular ; Protein Binding ; Protein Conformation ; Receptors, Glucagon/*chemistry/*metabolism ; }, abstract = {Class B G-protein-coupled receptors (GPCRs), which consist of an extracellular domain (ECD) and a transmembrane domain (TMD), respond to secretin peptides to play a key part in hormonal homeostasis, and are important therapeutic targets for a variety of diseases. Previous work has suggested that peptide ligands bind to class B GPCRs according to a two-domain binding model, in which the C-terminal region of the peptide targets the ECD and the N-terminal region of the peptide binds to the TMD binding pocket. Recently, three structures of class B GPCRs in complex with peptide ligands have been solved. These structures provide essential insights into peptide ligand recognition by class B GPCRs. However, owing to resolution limitations, the specific molecular interactions for peptide binding to class B GPCRs remain ambiguous. Moreover, these previously solved structures have different ECD conformations relative to the TMD, which introduces questions regarding inter-domain conformational flexibility and the changes required for receptor activation. Here we report the 3.0 Å-resolution crystal structure of the full-length human glucagon receptor (GCGR) in complex with a glucagon analogue and partial agonist, NNC1702. This structure provides molecular details of the interactions between GCGR and the peptide ligand. It reveals a marked change in the relative orientation between the ECD and TMD of GCGR compared to the previously solved structure of the inactive GCGR-NNC0640-mAb1 complex. Notably, the stalk region and the first extracellular loop undergo major conformational changes in secondary structure during peptide binding, forming key interactions with the peptide. We further propose a dual-binding-site trigger model for GCGR activation-which requires conformational changes of the stalk, first extracellular loop and TMD-that extends our understanding of the previously established two-domain peptide-binding model of class B GPCRs.}, } @article {pmid29300012, year = {2018}, author = {Sahoo, PK and Memaran, S and Xin, Y and Balicas, L and Gutiérrez, HR}, title = {One-pot growth of two-dimensional lateral heterostructures via sequential edge-epitaxy.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {63-67}, pmid = {29300012}, issn = {1476-4687}, abstract = {Two-dimensional heterojunctions of transition-metal dichalcogenides have great potential for application in low-power, high-performance and flexible electro-optical devices, such as tunnelling transistors, light-emitting diodes, photodetectors and photovoltaic cells. Although complex heterostructures have been fabricated via the van der Waals stacking of different two-dimensional materials, the in situ fabrication of high-quality lateral heterostructures with multiple junctions remains a challenge. Transition-metal-dichalcogenide lateral heterostructures have been synthesized via single-step, two-step or multi-step growth processes. However, these methods lack the flexibility to control, in situ, the growth of individual domains. In situ synthesis of multi-junction lateral heterostructures does not require multiple exchanges of sources or reactors, a limitation in previous approaches as it exposes the edges to ambient contamination, compromises the homogeneity of domain size in periodic structures, and results in long processing times. Here we report a one-pot synthetic approach, using a single heterogeneous solid source, for the continuous fabrication of lateral multi-junction heterostructures consisting of monolayers of transition-metal dichalcogenides. The sequential formation of heterojunctions is achieved solely by changing the composition of the reactive gas environment in the presence of water vapour. This enables selective control of the water-induced oxidation and volatilization of each transition-metal precursor, as well as its nucleation on the substrate, leading to sequential edge-epitaxy of distinct transition-metal dichalcogenides. Photoluminescence maps confirm the sequential spatial modulation of the bandgap, and atomic-resolution images reveal defect-free lateral connectivity between the different transition-metal-dichalcogenide domains within a single crystal structure. Electrical transport measurements revealed diode-like responses across the junctions. Our new approach offers greater flexibility and control than previous methods for continuous growth of transition-metal-dichalcogenide-based multi-junction lateral heterostructures. These findings could be extended to other families of two-dimensional materials, and establish a foundation for the development of complex and atomically thin in-plane superlattices, devices and integrated circuits.}, } @article {pmid29300011, year = {2018}, author = {Zilberberg, O and Huang, S and Guglielmon, J and Wang, M and Chen, KP and Kraus, YE and Rechtsman, MC}, title = {Photonic topological boundary pumping as a probe of 4D quantum Hall physics.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {59-62}, pmid = {29300011}, issn = {1476-4687}, abstract = {When a two-dimensional (2D) electron gas is placed in a perpendicular magnetic field, its in-plane transverse conductance becomes quantized; this is known as the quantum Hall effect. It arises from the non-trivial topology of the electronic band structure of the system, where an integer topological invariant (the first Chern number) leads to quantized Hall conductance. It has been shown theoretically that the quantum Hall effect can be generalized to four spatial dimensions, but so far this has not been realized experimentally because experimental systems are limited to three spatial dimensions. Here we use tunable 2D arrays of photonic waveguides to realize a dynamically generated four-dimensional (4D) quantum Hall system experimentally. The inter-waveguide separation in the array is constructed in such a way that the propagation of light through the device samples over momenta in two additional synthetic dimensions, thus realizing a 2D topological pump. As a result, the band structure has 4D topological invariants (known as second Chern numbers) that support a quantized bulk Hall response with 4D symmetry. In a finite-sized system, the 4D topological bulk response is carried by localized edge modes that cross the sample when the synthetic momenta are modulated. We observe this crossing directly through photon pumping of our system from edge to edge and corner to corner. These crossings are equivalent to charge pumping across a 4D system from one three-dimensional hypersurface to the spatially opposite one and from one 2D hyperedge to another. Our results provide a platform for the study of higher-dimensional topological physics.}, } @article {pmid29300010, year = {2018}, author = {Bourdeau, RW and Lee-Gosselin, A and Lakshmanan, A and Farhadi, A and Kumar, SR and Nety, SP and Shapiro, MG}, title = {Acoustic reporter genes for noninvasive imaging of microorganisms in mammalian hosts.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {86-90}, pmid = {29300010}, issn = {1476-4687}, support = {R01 EB018975/EB/NIBIB NIH HHS/United States ; }, mesh = {*Acoustics ; Animals ; Escherichia coli/genetics/isolation & purification ; Female ; Gases/analysis ; Gastrointestinal Tract/*microbiology ; Gene Expression Regulation, Bacterial ; *Genes, Bacterial ; Genes, Reporter/*genetics ; Genetic Engineering ; Heterografts ; High-Throughput Screening Assays ; Humans ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Mice, SCID ; Multigene Family/genetics ; Nanostructures/analysis ; Neoplasm Transplantation ; Ovarian Neoplasms/*microbiology ; Photosynthesis ; Proteins/*genetics/metabolism ; Salmonella typhimurium/genetics/isolation & purification ; Ultrasonography/*methods ; }, abstract = {The mammalian microbiome has many important roles in health and disease, and genetic engineering is enabling the development of microbial therapeutics and diagnostics. A key determinant of the activity of both natural and engineered microorganisms in vivo is their location within the host organism. However, existing methods for imaging cellular location and function, primarily based on optical reporter genes, have limited deep tissue performance owing to light scattering or require radioactive tracers. Here we introduce acoustic reporter genes, which are genetic constructs that allow bacterial gene expression to be visualized in vivo using ultrasound, a widely available inexpensive technique with deep tissue penetration and high spatial resolution. These constructs are based on gas vesicles, a unique class of gas-filled protein nanostructures that are expressed primarily in water-dwelling photosynthetic organisms as a means to regulate buoyancy. Heterologous expression of engineered gene clusters encoding gas vesicles allows Escherichia coli and Salmonella typhimurium to be imaged noninvasively at volumetric densities below 0.01% with a resolution of less than 100 μm. We demonstrate the imaging of engineered cells in vivo in proof-of-concept models of gastrointestinal and tumour localization, and develop acoustically distinct reporters that enable multiplexed imaging of cellular populations. This technology equips microbial cells with a means to be visualized deep inside mammalian hosts, facilitating the study of the mammalian microbiome and the development of diagnostic and therapeutic cellular agents.}, } @article {pmid29300009, year = {2018}, author = {Robertson, N and Rappas, M and Doré, AS and Brown, J and Bottegoni, G and Koglin, M and Cansfield, J and Jazayeri, A and Cooke, RM and Marshall, FH}, title = {Structure of the complement C5a receptor bound to the extra-helical antagonist NDT9513727.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {111-114}, pmid = {29300009}, issn = {1476-4687}, mesh = {Animals ; Benzodioxoles/*chemistry/*metabolism/pharmacology ; Binding Sites ; Crystallography, X-Ray ; Drug Inverse Agonism ; HEK293 Cells ; Humans ; Imidazoles/*chemistry/*metabolism/pharmacology ; Models, Molecular ; Mutation ; Protein Stability ; Protein Structure, Secondary ; Receptor, Anaphylatoxin C5a/*antagonists & inhibitors/*chemistry/genetics/metabolism ; Receptors, Adrenergic, beta-2/chemistry/metabolism ; Receptors, G-Protein-Coupled/chemistry/metabolism ; }, abstract = {The complement system is a crucial component of the host response to infection and tissue damage. Activation of the complement cascade generates anaphylatoxins including C5a and C3a. C5a exerts a pro-inflammatory effect via the G-protein-coupled receptor C5a anaphylatoxin chemotactic receptor 1 (C5aR1, also known as CD88) that is expressed on cells of myeloid origin. Inhibitors of the complement system have long been of interest as potential drugs for the treatment of diseases such as sepsis, rheumatoid arthritis, Crohn's disease and ischaemia-reperfusion injuries. More recently, a role of C5a in neurodegenerative conditions such as Alzheimer's disease has been identified. Peptide antagonists based on the C5a ligand have progressed to phase 2 trials in psoriasis and rheumatoid arthritis; however, these compounds exhibited problems with off-target activity, production costs, potential immunogenicity and poor oral bioavailability. Several small-molecule competitive antagonists for C5aR1, such as W-54011 and NDT9513727, have been identified by C5a radioligand-binding assays. NDT9513727 is a non-peptide inverse agonist of C5aR1, and is highly selective for the primate and gerbil receptors over those of other species. Here, to study the mechanism of action of C5a antagonists, we determine the structure of a thermostabilized C5aR1 (known as C5aR1 StaR) in complex with NDT9513727. We found that the small molecule bound between transmembrane helices 3, 4 and 5, outside the helical bundle. One key interaction between the small molecule and residue Trp2135.49 seems to determine the species selectivity of the compound. The structure demonstrates that NDT9513727 exerts its inverse-agonist activity through an extra-helical mode of action.}, } @article {pmid29300008, year = {2018}, author = {Bereiter, B and Shackleton, S and Baggenstos, D and Kawamura, K and Severinghaus, J}, title = {Mean global ocean temperatures during the last glacial transition.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {39-44}, pmid = {29300008}, issn = {1476-4687}, mesh = {Antarctic Regions ; Atmosphere/chemistry ; Carbon Dioxide/analysis ; Climate ; History, 21st Century ; History, Ancient ; Hot Temperature ; Ice Cover/*chemistry ; Noble Gases/analysis ; *Oceans and Seas ; Seasons ; *Temperature ; }, abstract = {Little is known about the ocean temperature's long-term response to climate perturbations owing to limited observations and a lack of robust reconstructions. Although most of the anthropogenic heat added to the climate system has been taken up by the ocean up until now, its role in a century and beyond is uncertain. Here, using noble gases trapped in ice cores, we show that the mean global ocean temperature increased by 2.57 ± 0.24 degrees Celsius over the last glacial transition (20,000 to 10,000 years ago). Our reconstruction provides unprecedented precision and temporal resolution for the integrated global ocean, in contrast to the depth-, region-, organism- and season-specific estimates provided by other methods. We find that the mean global ocean temperature is closely correlated with Antarctic temperature and has no lead or lag with atmospheric CO2, thereby confirming the important role of Southern Hemisphere climate in global climate trends. We also reveal an enigmatic 700-year warming during the early Younger Dryas period (about 12,000 years ago) that surpasses estimates of modern ocean heat uptake.}, } @article {pmid29300007, year = {2018}, author = {Palesch, D and Bosinger, SE and Tharp, GK and Vanderford, TH and Paiardini, M and Chahroudi, A and Johnson, ZP and Kirchhoff, F and Hahn, BH and Norgren, RB and Patel, NB and Sodora, DL and Dawoud, RA and Stewart, CB and Seepo, SM and Harris, RA and Liu, Y and Raveendran, M and Han, Y and English, A and Thomas, GWC and Hahn, MW and Pipes, L and Mason, CE and Muzny, DM and Gibbs, RA and Sauter, D and Worley, K and Rogers, J and Silvestri, G}, title = {Sooty mangabey genome sequence provides insight into AIDS resistance in a natural SIV host.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {77-81}, pmid = {29300007}, issn = {1476-4687}, support = {P30 AI050409/AI/NIAID NIH HHS/United States ; R24 OD010445/OD/NIH HHS/United States ; P51 OD011132/OD/NIH HHS/United States ; U54 HG003273/HG/NHGRI NIH HHS/United States ; U54-HG006484-01/NH/NIH HHS/United States ; R37 AI066998/AI/NIAID NIH HHS/United States ; R37 AI050529/AI/NIAID NIH HHS/United States ; R01 AI066998/AI/NIAID NIH HHS/United States ; }, mesh = {Acquired Immunodeficiency Syndrome/*genetics/virology ; Amino Acid Sequence ; Animals ; Cell Adhesion Molecules/chemistry/genetics/metabolism ; Cercocebus atys/*genetics/immunology/*virology ; Exons/genetics ; Female ; Frameshift Mutation/genetics ; *Genetic Predisposition to Disease ; Genetic Variation ; Genome/*genetics ; Genomics ; HIV/pathogenicity ; Host Specificity/*genetics ; Humans ; Macaca/virology ; Sequence Deletion ; Simian Acquired Immunodeficiency Syndrome/genetics/virology ; *Simian Immunodeficiency Virus/pathogenicity ; Species Specificity ; Toll-Like Receptor 4/chemistry/genetics/immunology ; Transcriptome/genetics ; Whole Genome Sequencing ; }, abstract = {In contrast to infections with human immunodeficiency virus (HIV) in humans and simian immunodeficiency virus (SIV) in macaques, SIV infection of a natural host, sooty mangabeys (Cercocebus atys), is non-pathogenic despite high viraemia. Here we sequenced and assembled the genome of a captive sooty mangabey. We conducted genome-wide comparative analyses of transcript assemblies from C. atys and AIDS-susceptible species, such as humans and macaques, to identify candidates for host genetic factors that influence susceptibility. We identified several immune-related genes in the genome of C. atys that show substantial sequence divergence from macaques or humans. One of these sequence divergences, a C-terminal frameshift in the toll-like receptor-4 (TLR4) gene of C. atys, is associated with a blunted in vitro response to TLR-4 ligands. In addition, we found a major structural change in exons 3-4 of the immune-regulatory protein intercellular adhesion molecule 2 (ICAM-2); expression of this variant leads to reduced cell surface expression of ICAM-2. These data provide a resource for comparative genomic studies of HIV and/or SIV pathogenesis and may help to elucidate the mechanisms by which SIV-infected sooty mangabeys avoid AIDS.}, } @article {pmid29300006, year = {2018}, author = {Lohse, M and Schweizer, C and Price, HM and Zilberberg, O and Bloch, I}, title = {Exploring 4D quantum Hall physics with a 2D topological charge pump.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {55-58}, pmid = {29300006}, issn = {1476-4687}, abstract = {The discovery of topological states of matter has greatly improved our understanding of phase transitions in physical systems. Instead of being described by local order parameters, topological phases are described by global topological invariants and are therefore robust against perturbations. A prominent example is the two-dimensional (2D) integer quantum Hall effect: it is characterized by the first Chern number, which manifests in the quantized Hall response that is induced by an external electric field. Generalizing the quantum Hall effect to four-dimensional (4D) systems leads to the appearance of an additional quantized Hall response, but one that is nonlinear and described by a 4D topological invariant-the second Chern number. Here we report the observation of a bulk response with intrinsic 4D topology and demonstrate its quantization by measuring the associated second Chern number. By implementing a 2D topological charge pump using ultracold bosonic atoms in an angled optical superlattice, we realize a dynamical version of the 4D integer quantum Hall effect. Using a small cloud of atoms as a local probe, we fully characterize the nonlinear response of the system via in situ imaging and site-resolved band mapping. Our findings pave the way to experimentally probing higher-dimensional quantum Hall systems, in which additional strongly correlated topological phases, exotic collective excitations and boundary phenomena such as isolated Weyl fermions are predicted.}, } @article {pmid29299623, year = {2018}, author = {da Silva Ribeiro, A and Polonio, JC and Costa, AT and Dos Santos, CM and Rhoden, SA and Azevedo, JL and Pamphile, JA}, title = {Bioprospection of Culturable Endophytic Fungi Associated with the Ornamental Plant Pachystachys lutea.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {588-596}, pmid = {29299623}, issn = {1432-0991}, support = {311534/2014-7//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 447265/2014-8//Conselho Nacional de Desenvolvimento Científico e Tecnológico/ ; 276/2014//Fundação Araucária/ ; }, mesh = {Antibiosis ; Colletotrichum/physiology ; Endophytes/classification/genetics/*isolation & purification/*physiology ; Fungi/classification/genetics/*isolation & purification/*physiology ; Fusarium/physiology ; Magnoliopsida/growth & development/*microbiology ; Phylogeny ; Plant Diseases/microbiology/*prevention & control ; Plant Leaves/microbiology ; }, abstract = {Endophytes are fungi and bacteria that inhabit plant tissues without causing disease. Endophytes have characteristics that are important for the health of the plant and have been isolated from several plants of economic and medicinal interest but rarely from ornamental plants. The current study isolates and identifies endophytic fungi from the leaves of Pachystachys lutea and evaluates the antagonistic activity of these endophytes as well as cellulase production by the endophytes. Fungi were isolated by fragmentation from surface-disinfected leaves and were identified by the sequencing of the ITS gene and the genes coding for EF 1-α and β-tubulin followed by multilocus sequence analysis. Molecular taxonomic analysis revealed that 78% of the identified fungi belonged to the genus Diaporthe. We also identified strains belonging to the genera Colletotrichum, Phyllosticta, Xylaria, Nemania, and Alternaria. Most of the strains tested were able to inhibit the growth of pathogenic fungi, especially PL09 (Diaporthe sp.), which inhibited the growth of Colletotrichum sp., and PL03 (Diaporthe sp.), which inhibited the growth of Fusarium oxysporum. The production of cellulase ranged from 0.87 to 1.60 μmol/min. Foliar endophytic fungal isolates from P. lutea showed promising results for the in vitro control of plant pathogens and for cellulase production. This paper is the first report on culturable endophytic fungi isolated from the ornamental plant P. lutea.}, } @article {pmid29298915, year = {2018}, author = {Valzania, L and Coon, KL and Vogel, KJ and Brown, MR and Strand, MR}, title = {Hypoxia-induced transcription factor signaling is essential for larval growth of the mosquito Aedes aegypti.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {457-465}, pmid = {29298915}, issn = {1091-6490}, support = {R01 AI106892/AI/NIAID NIH HHS/United States ; T32 GM007103/GM/NIGMS NIH HHS/United States ; }, mesh = {AMP-Activated Protein Kinases/genetics/metabolism ; Aedes/genetics/growth & development/*metabolism ; Animals ; Aryl Hydrocarbon Receptor Nuclear Translocator/genetics/*metabolism ; Fat Body/growth & development/metabolism ; Female ; Hypoxia-Inducible Factor 1, alpha Subunit/genetics/*metabolism ; Insect Proteins/genetics/*metabolism ; Larva/genetics/*growth & development/metabolism ; Male ; Oxygen/metabolism ; Signal Transduction ; }, abstract = {Gut microbes positively affect the physiology of many animals, but the molecular mechanisms underlying these benefits remain poorly understood. We recently reported that bacteria-induced gut hypoxia functions as a signal for growth and molting of the mosquito Aedes aegypti In this study, we tested the hypothesis that transduction of a gut hypoxia signal requires hypoxia-induced transcription factors (HIFs). Expression studies showed that HIF-α was stabilized in larvae containing bacteria that induce gut hypoxia but was destabilized in larvae that exhibit normoxia. However, we could rescue growth of larvae exhibiting gut normoxia by treating them with a prolyl hydroxylase inhibitor, FG-4592, that stabilized HIF-α, and inhibit growth of larvae exhibiting gut hypoxia by treating them with an inhibitor, PX-478, that destabilized HIF-α. Using these tools, we determined that HIF signaling activated the insulin/insulin growth factor pathway plus select mitogen-activated kinases and inhibited the adenosine monophosphate-activated protein kinase pathway. HIF signaling was also required for growth of the larval midgut and storage of neutral lipids by the fat body. Altogether, our results indicate that gut hypoxia and HIF signaling activate multiple processes in A. aegypti larvae, with conserved functions in growth and metabolism.}, } @article {pmid29298914, year = {2018}, author = {Hoernes, TP and Clementi, N and Juen, MA and Shi, X and Faserl, K and Willi, J and Gasser, C and Kreutz, C and Joseph, S and Lindner, H and Hüttenhofer, A and Erlacher, MD}, title = {Atomic mutagenesis of stop codon nucleotides reveals the chemical prerequisites for release factor-mediated peptide release.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E382-E389}, pmid = {29298914}, issn = {1091-6490}, mesh = {Codon, Terminator/*genetics ; Escherichia coli/*metabolism ; Escherichia coli Proteins/metabolism ; Mutagenesis, Site-Directed ; Nucleotides ; Peptide Chain Termination, Translational ; Peptide Termination Factors/*physiology ; Protein Biosynthesis ; }, abstract = {Termination of protein synthesis is triggered by the recognition of a stop codon at the ribosomal A site and is mediated by class I release factors (RFs). Whereas in bacteria, RF1 and RF2 promote termination at UAA/UAG and UAA/UGA stop codons, respectively, eukaryotes only depend on one RF (eRF1) to initiate peptide release at all three stop codons. Based on several structural as well as biochemical studies, interactions between mRNA, tRNA, and rRNA have been proposed to be required for stop codon recognition. In this study, the influence of these interactions was investigated by using chemically modified stop codons. Single functional groups within stop codon nucleotides were substituted to weaken or completely eliminate specific interactions between the respective mRNA and RFs. Our findings provide detailed insight into the recognition mode of bacterial and eukaryotic RFs, thereby revealing the chemical groups of nucleotides that define the identity of stop codons and provide the means to discriminate against noncognate stop codons or UGG sense codons.}, } @article {pmid29298913, year = {2018}, author = {Kilcher, S and Studer, P and Muessner, C and Klumpp, J and Loessner, MJ}, title = {Cross-genus rebooting of custom-made, synthetic bacteriophage genomes in L-form bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {567-572}, pmid = {29298913}, issn = {1091-6490}, mesh = {Bacteriophages/classification/*genetics/physiology ; Genome, Viral ; Gram-Positive Bacteria/physiology/virology ; Listeria monocytogenes/physiology/*virology ; Synthetic Biology ; }, abstract = {Engineered bacteriophages provide powerful tools for biotechnology, diagnostics, pathogen control, and therapy. However, current techniques for phage editing are experimentally challenging and limited to few phages and host organisms. Viruses that target Gram-positive bacteria are particularly difficult to modify. Here, we present a platform technology that enables rapid, accurate, and selection-free construction of synthetic, tailor-made phages that infect Gram-positive bacteria. To this end, custom-designed, synthetic phage genomes were assembled in vitro from smaller DNA fragments. We show that replicating, cell wall-deficient Listeria monocytogenes L-form bacteria can reboot synthetic phage genomes upon transfection, i.e., produce virus particles from naked, synthetic DNA. Surprisingly, Listeria L-form cells not only support rebooting of native and synthetic Listeria phage genomes but also enable cross-genus reactivation of Bacillus and Staphylococcus phages from their DNA, thereby broadening the approach to phages that infect other important Gram-positive pathogens. We then used this platform to generate virulent phages by targeted modification of temperate phage genomes and demonstrated their superior killing efficacy. These synthetic, virulent phages were further armed by incorporation of enzybiotics into their genomes as a genetic payload, which allowed targeting of phage-resistant bystander cells. In conclusion, this straightforward and robust synthetic biology approach redefines the possibilities for the development of improved and completely new phage applications, including phage therapy.}, } @article {pmid29298912, year = {2018}, author = {Mundinano, IC and Fox, DM and Kwan, WC and Vidaurre, D and Teo, L and Homman-Ludiye, J and Goodale, MA and Leopold, DA and Bourne, JA}, title = {Transient visual pathway critical for normal development of primate grasping behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1364-1369}, pmid = {29298912}, issn = {1091-6490}, support = {ZIA MH002838/MH/NIMH NIH HHS/United States ; ZIA MH002898/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Animals, Newborn ; Callithrix/*physiology ; Diffusion Magnetic Resonance Imaging/methods ; Female ; Hand Strength/*physiology ; Male ; Neurons/physiology ; Parietal Lobe/anatomy & histology/physiology ; Pulvinar/*physiology ; Visual Pathways/*physiology ; }, abstract = {An evolutionary hallmark of anthropoid primates, including humans, is the use of vision to guide precise manual movements. These behaviors are reliant on a specialized visual input to the posterior parietal cortex. Here, we show that normal primate reaching-and-grasping behavior depends critically on a visual pathway through the thalamic pulvinar, which is thought to relay information to the middle temporal (MT) area during early life and then swiftly withdraws. Small MRI-guided lesions to a subdivision of the inferior pulvinar subnucleus (PIm) in the infant marmoset monkey led to permanent deficits in reaching-and-grasping behavior in the adult. This functional loss coincided with the abnormal anatomical development of multiple cortical areas responsible for the guidance of actions. Our study reveals that the transient retino-pulvinar-MT pathway underpins the development of visually guided manual behaviors in primates that are crucial for interacting with complex features in the environment.}, } @article {pmid29298911, year = {2018}, author = {Grossman-Haham, I and Rosenblum, G and Namani, T and Hofmann, H}, title = {Slow domain reconfiguration causes power-law kinetics in a two-state enzyme.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {513-518}, pmid = {29298911}, issn = {1091-6490}, mesh = {Electron Transport ; Kinetics ; Oxidoreductases/*chemistry/metabolism ; Protein Conformation ; Protein Domains ; Protozoan Proteins/*chemistry/metabolism ; Trypanosoma brucei brucei/chemistry/*enzymology ; }, abstract = {Protein dynamics are typically captured well by rate equations that predict exponential decays for two-state reactions. Here, we describe a remarkable exception. The electron-transfer enzyme quiescin sulfhydryl oxidase (QSOX), a natural fusion of two functionally distinct domains, switches between open- and closed-domain arrangements with apparent power-law kinetics. Using single-molecule FRET experiments on time scales from nanoseconds to milliseconds, we show that the unusual open-close kinetics results from slow sampling of an ensemble of disordered domain orientations. While substrate accelerates the kinetics, thus suggesting a substrate-induced switch to an alternative free energy landscape of the enzyme, the power-law behavior is also preserved upon electron load. Our results show that the slow sampling of open conformers is caused by a variety of interdomain interactions that imply a rugged free energy landscape, thus providing a generic mechanism for dynamic disorder in multidomain enzymes.}, } @article {pmid29298732, year = {2018}, author = {Luna, PN and Hasegawa, K and Ajami, NJ and Espinola, JA and Henke, DM and Petrosino, JF and Piedra, PA and Sullivan, AF and Camargo, CA and Shaw, CA and Mansbach, JM}, title = {The association between anterior nares and nasopharyngeal microbiota in infants hospitalized for bronchiolitis.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {2}, pmid = {29298732}, issn = {2049-2618}, support = {R01 AI-114552/NH/NIH HHS/United States ; UG3 OD-023253/NH/NIH HHS/United States ; R01 AI-108588/NH/NIH HHS/United States ; R01 AI108588/AI/NIAID NIH HHS/United States ; UG3 OD023253/OD/NIH HHS/United States ; U01 AI-087881/NH/NIH HHS/United States ; }, mesh = {Bronchiolitis/*microbiology ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Female ; Hospitalization ; Humans ; Infant ; Longitudinal Studies ; Male ; Microbiota ; Nasal Cavity/*microbiology ; Nasopharynx/*microbiology ; RNA, Ribosomal, 16S/*genetics ; Sequence Analysis, DNA/*methods ; Staphylococcus/classification/genetics/*isolation & purification ; }, abstract = {BACKGROUND: The airway microbiome is a subject of great interest for the study of respiratory disease. Anterior nare samples are more accessible than samples from deeper within the nasopharynx. However, the correlation between the microbiota found in the anterior nares and the microbiota found within the nasopharynx is unknown. We assessed the anterior nares and nasopharyngeal microbiota to determine (1) the relation of the microbiota from these two upper airway sites and (2) if associations were maintained between the microbiota from these two sites and two bronchiolitis severity outcomes.

RESULTS: Among 815 infants hospitalized at 17 US centers for bronchiolitis with optimal 16S rRNA gene sequence reads from both nasal swab and nasopharyngeal aspirate samples, there were strong intra-individual correlations in the microbial communities between the two sample types, especially relating to Haemophilus and Moraxella genera. By contrast, we found a high abundance of Staphylococcus genus in the nasal swabs-a pattern not found in the nasopharyngeal samples and not informative when predicting the dominant nasopharyngeal genera. While these disparities may have been due to sample processing differences (i.e., nasal swabs were mailed at ambient temperature to emulate processing of future parent collected swabs while nasopharyngeal aspirates were mailed on dry ice), a previously reported association between Haemophilus-dominant nasopharyngeal microbiota and the increased severity of bronchiolitis was replicated utilizing the nasal swab microbiota and the same outcome measures: intensive care use (adjusted OR 6.43; 95% CI 2.25-20.51; P < 0.001) and hospital length-of-stay (adjusted OR 4.31; 95% CI, 1.73-11.11; P = 0.002). Additionally, Moraxella-dominant nasopharyngeal microbiota was previously identified as protective against intensive care use, a result that was replicated when analyzing the nasal swab microbiota (adjusted OR 0.30; 95% CI, 0.11-0.64; P = 0.01).

CONCLUSIONS: While the microbiota of the anterior nares and the nasopharynx are distinct, there is considerable overlap between the bacterial community compositions from these two anatomic sites. Despite processing differences between the samples, these results indicate that microbiota severity associations from the nasopharynx are recapitulated in the anterior nares, suggesting that nasal swab samples not only are effective sample types, but also can be used to detect microbial risk markers.}, } @article {pmid29298731, year = {2018}, author = {Ravignani, A}, title = {Spontaneous rhythms in a harbor seal pup calls.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {3}, pmid = {29298731}, issn = {1756-0500}, support = {Marie Skłodowska-Curie grant agreement No 665501//Horizon 2020/ ; }, mesh = {Animals ; Female ; Phoca/*physiology ; Sound Spectrography ; Time Factors ; Vocalization, Animal/*physiology ; }, abstract = {OBJECTIVES: Timing and rhythm (i.e. temporal structure) are crucial, though historically neglected, dimensions of animal communication. When investigating these in non-human animals, it is often difficult to balance experimental control and ecological validity. Here I present the first step of an attempt to balance the two, focusing on the timing of vocal rhythms in a harbor seal pup (Phoca vitulina). Collection of this data had a clear aim: To find spontaneous vocal rhythms in this individual in order to design individually-adapted and ecologically-relevant stimuli for a later playback experiment.

DATA DESCRIPTION: The calls of one seal pup were recorded. The audio recordings were annotated using Praat, a free software to analyze vocalizations in humans and other animals. The annotated onsets and offsets of vocalizations were then imported in a Python script. The script extracted three types of timing information: the duration of calls, the intervals between calls' onsets, and the intervals between calls' maximum-intensity peaks. Based on the annotated data, available to download, I provide simple descriptive statistics for these temporal measures, and compare their distributions.}, } @article {pmid29298729, year = {2018}, author = {Marasco, R and Rolli, E and Fusi, M and Michoud, G and Daffonchio, D}, title = {Grapevine rootstocks shape underground bacterial microbiome and networking but not potential functionality.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {3}, pmid = {29298729}, issn = {2049-2618}, mesh = {Bacteria/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; High-Throughput Nucleotide Sequencing/*methods ; Microbiota ; Phylogeny ; Plant Roots/microbiology ; RNA, Ribosomal, 16S/*genetics ; Rhizosphere ; Sequence Analysis, DNA/*methods ; Soil Microbiology ; Vitis/*microbiology ; }, abstract = {BACKGROUND: The plant compartments of Vitis vinifera, including the rhizosphere, rhizoplane, root endosphere, phyllosphere and carposphere, provide unique niches that drive specific bacterial microbiome associations. The majority of phyllosphere endophytes originate from the soil and migrate up to the aerial compartments through the root endosphere. Thus, the soil and root endosphere partially define the aerial endosphere in the leaves and berries, contributing to the terroir of the fruit. However, V. vinifera cultivars are invariably grafted onto the rootstocks of other Vitis species and hybrids. It has been hypothesized that the plant species determines the microbiome of the root endosphere and, as a consequence, the aerial endosphere. In this work, we test the first part of this hypothesis. We investigate whether different rootstocks influence the bacteria selected from the surrounding soil, affecting the bacterial diversity and potential functionality of the rhizosphere and root endosphere.

METHODS: Bacterial microbiomes from both the root tissues and the rhizosphere of Barbera cultivars, both ungrafted and grafted on four different rootstocks, cultivated in the same soil from the same vineyard, were characterized by 16S rRNA high-throughput sequencing. To assess the influence of the root genotype on the bacterial communities' recruitment in the root system, (i) the phylogenetic diversity coupled with the predicted functional profiles and (ii) the co-occurrence bacterial networks were determined. Cultivation-dependent approaches were used to reveal the plant-growth promoting (PGP) potential associated with the grafted and ungrafted root systems.

RESULTS: Richness, diversity and bacterial community networking in the root compartments were significantly influenced by the rootstocks. Complementary to a shared bacterial microbiome, different subsets of soil bacteria, including those endowed with PGP traits, were selected by the root system compartments of different rootstocks. The interaction between the root compartments and the rootstock exerted a unique selective pressure that enhanced niche differentiation, but rootstock-specific bacterial communities were still recruited with conserved PGP traits.

CONCLUSION: While the rootstock significantly influences the taxonomy, structure and network properties of the bacterial community in grapevine roots, a homeostatic effect on the distribution of the predicted and potential functional PGP traits was found.}, } @article {pmid29298721, year = {2018}, author = {Nabbe, P and Le Reste, JY and Guillou-Landreat, M and Beck-Robert, E and Assenova, R and Lazic, D and Czachowski, S and Stojanović-Špehar, S and Hasanagic, M and Lingner, H and Clavería, A and Fernandez San Martin, MI and Sowinska, A and Argyriadou, S and Lygidakis, C and Le Floch, B and Doerr, C and Montier, T and Van Marwijk, H and Van Royen, P}, title = {One consensual depression diagnosis tool to serve many countries: a challenge! A RAND/UCLA methodology.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {4}, pmid = {29298721}, issn = {1756-0500}, support = {8000//EGPRN/ ; }, mesh = {*Consensus ; *Delphi Technique ; Depression/*diagnosis ; Depressive Disorder/*diagnosis ; Europe ; Humans ; Psychiatric Status Rating Scales/*standards ; }, abstract = {OBJECTIVE: From a systematic literature review (SLR), it became clear that a consensually validated tool was needed by European General Practitioner (GP) researchers in order to allow multi-centred collaborative research, in daily practice, throughout Europe. Which diagnostic tool for depression, validated against psychiatric examination according to the DSM, would GPs select as the best for use in clinical research, taking into account the combination of effectiveness, reliability and ergonomics? A RAND/UCLA, which combines the qualities of the Delphi process and of the nominal group, was used. GP researchers from different European countries were selected. The SLR extracted tools were validated against the DSM. The Youden index was used as an effectiveness criterion and Cronbach's alpha as a reliability criterion. Ergonomics data were extracted from the literature. Ergonomics were tested face-to-face.

RESULTS: The SLR extracted 7 tools. Two instruments were considered sufficiently effective and reliable for use: the Hospital Anxiety and Depression Scale and the Hopkins Symptoms Checklist-25 (HSCL-25). After testing face-to-face, HSCL-25 was selected. A multicultural consensus on one diagnostic tool for depression was obtained for the HSCL-25. This tool will provide the opportunity to select homogeneous populations for European collaborative research in daily practice.}, } @article {pmid29298685, year = {2018}, author = {Kuno, A and Nishimura, K and Takahashi, S}, title = {Time-course transcriptome analysis of human cellular reprogramming from multiple cell types reveals the drastic change occurs between the mid phase and the late phase.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {9}, pmid = {29298685}, issn = {1471-2164}, mesh = {Cellular Reprogramming/*genetics ; Gene Expression Profiling ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Kinetics ; Transcription Factors/metabolism ; *Transcriptome ; }, abstract = {BACKGROUND: Human induced pluripotent stem cells (hiPSCs) have been attempted for clinical application with diverse iPSCs sources derived from various cell types. This proposes that there would be a shared reprogramming route regardless of different starting cell types. However, the insights of reprogramming process are mostly restricted to only fibroblasts of both human and mouse. To understand molecular mechanisms of cellular reprogramming, the investigation of the conserved reprogramming routes from various cell types is needed. Particularly, the maturation, belonging to the mid phase of reprogramming, was reported as the main roadblock of reprogramming from human dermal fibroblasts to hiPSCs. Therefore, we investigated first whether the shared reprogramming routes exists across various human cell types and second whether the maturation is also a major blockage of reprogramming in various cell types.

RESULTS: We selected 3615 genes with dynamic expressions during reprogramming from five human starting cell types by using time-course microarray dataset. Then, we analyzed transcriptomic variances, which were clustered into 3 distinct transcriptomic phases (early, mid and late phase); and greatest difference lied in the late phase. Moreover, functional annotation of gene clusters classified by gene expression patterns showed the mesenchymal-epithelial transition from day 0 to 3, transient upregulation of epidermis related genes from day 7 to 15, and upregulation of pluripotent genes from day 20, which were partially similar to the reprogramming process of mouse embryonic fibroblasts. We lastly illustrated variations of transcription factor activity at each time point of the reprogramming process and a major differential transition of transcriptome in between day 15 to 20 regardless of cell types. Therefore, the results implied that the maturation would be a major roadblock across multiple cell types in the human reprogramming process.

CONCLUSIONS: Human cellular reprogramming process could be traced into three different phases across various cell types. As the late phase exhibited the greatest dissimilarity, the maturation step could be suggested as the common major roadblock during human cellular reprogramming. To understand further molecular mechanisms of the maturation would enhance reprogramming efficiency by overcoming the roadblock during hiPSCs generation.}, } @article {pmid29298683, year = {2018}, author = {Cortés-López, M and Gruner, MR and Cooper, DA and Gruner, HN and Voda, AI and van der Linden, AM and Miura, P}, title = {Global accumulation of circRNAs during aging in Caenorhabditis elegans.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {8}, pmid = {29298683}, issn = {1471-2164}, support = {P40 OD010440/OD/NIH HHS/United States ; P20 GM103650/GM/NIGMS NIH HHS/United States ; R15AG052931/AG/NIA NIH HHS/United States ; R15 AG052931/AG/NIA NIH HHS/United States ; P20GM103650//National Institute of General Medical Sciences (US)/International ; }, mesh = {Aging/*genetics ; Animals ; Caenorhabditis elegans/*genetics/metabolism ; Gene Expression Profiling ; Genomics ; High-Throughput Nucleotide Sequencing ; RNA/*metabolism ; Sequence Analysis, RNA ; }, abstract = {BACKGROUND: Circular RNAs (CircRNAs) are a newly appreciated class of RNAs that lack free 5' and 3' ends, are expressed by the thousands in diverse forms of life, and are mostly of enigmatic function. Ostensibly due to their resistance to exonucleases, circRNAs are known to be exceptionally stable. Previous work in Drosophila and mice have shown that circRNAs increase during aging in neural tissues.

RESULTS: Here, we examined the global profile of circRNAs in C. elegans during aging by performing ribo-depleted total RNA-seq from the fourth larval stage (L4) through 10-day old adults. Using stringent bioinformatic criteria and experimental validation, we annotated a high-confidence set of 1166 circRNAs, including 575 newly discovered circRNAs. These circRNAs were derived from 797 genes with diverse functions, including genes involved in the determination of lifespan. A massive accumulation of circRNAs during aging was uncovered. Many hundreds of circRNAs were significantly increased among the aging time-points and increases of select circRNAs by over 40-fold during aging were quantified by RT-qPCR. The expression of 459 circRNAs was determined to be distinct from the expression of linear RNAs from the same host genes, demonstrating host gene independence of circRNA age-accumulation.

CONCLUSIONS: We attribute the global scale of circRNA age-accumulation to the high composition of post-mitotic cells in adult C. elegans, coupled with the high resistance of circRNAs to decay. These findings suggest that the exceptional stability of circRNAs might explain age-accumulation trends observed from neural tissues of other organisms, which also have a high composition of post-mitotic cells. Given the suitability of C. elegans for aging research, it is now poised as an excellent model system to determine whether there are functional consequences of circRNA accumulation during aging.}, } @article {pmid29298680, year = {2018}, author = {Schedina, IM and Groth, D and Schlupp, I and Tiedemann, R}, title = {The gonadal transcriptome of the unisexual Amazon molly Poecilia formosa in comparison to its sexual ancestors, Poecilia mexicana and Poecilia latipinna.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {12}, pmid = {29298680}, issn = {1471-2164}, support = {NA//Universität Potsdam/International ; NA//Universität Potsdam/International ; NA//Alexander von Humboldt-Stiftung/International ; }, mesh = {Animals ; Gene Expression Profiling ; Gonads/*metabolism ; High-Throughput Nucleotide Sequencing ; Meiosis/genetics ; Parthenogenesis/genetics ; Poecilia/*genetics/metabolism ; Sequence Analysis, RNA ; *Transcriptome ; }, abstract = {BACKGROUND: The unisexual Amazon molly (Poecilia formosa) originated from a hybridization between two sexual species, the sailfin molly (Poecilia latipinna) and the Atlantic molly (Poecilia mexicana). The Amazon molly reproduces clonally via sperm-dependent parthenogenesis (gynogenesis), in which the sperm of closely related species triggers embryogenesis of the apomictic oocytes, but typically does not contribute genetic material to the next generation. We compare for the first time the gonadal transcriptome of the Amazon molly to those of both ancestral species, P. mexicana and P. latipinna.

RESULTS: We sequenced the gonadal transcriptomes of the P. formosa and its parental species P. mexicana and P. latipinna using Illumina RNA-sequencing techniques (paired-end, 100 bp). De novo assembly of about 50 million raw read pairs for each species was performed using Trinity, yielding 106,922 transcripts for P. formosa, 115,175 for P. latipinna, and 133,025 for P. mexicana after eliminating contaminations. On the basis of sequence similarity comparisons to other teleost species and the UniProt databases, functional annotation, and differential expression analysis, we demonstrate the similarity of the transcriptomes among the three species. More than 40% of the transcripts for each species were functionally annotated and about 70% were assigned to orthologous genes of a closely related species. Differential expression analysis between the sexual and unisexual species uncovered 2035 up-regulated and 564 down-regulated genes in P. formosa. This was exemplary validated for six genes by qRT-PCR.

CONCLUSIONS: We identified more than 130 genes related to meiosis and reproduction within the apomictically reproducing P. formosa. Overall expression of these genes seems to be down-regulated in the P. formosa transcriptome compared to both ancestral species (i.e., 106 genes down-regulated, 29 up-regulated). A further 35 meiosis and reproduction related genes were not found in the P. formosa transcriptome, but were only expressed in the sexual species. Our data support the hypothesis of general down-regulation of meiosis-related genes in the apomictic Amazon molly. Furthermore, the obtained dataset and identified gene catalog will serve as a resource for future research on the molecular mechanisms behind the reproductive mode of this unisexual species.}, } @article {pmid29298679, year = {2018}, author = {Caldonazzo Garbelini, JM and Kashiwabara, AY and Sanches, DS}, title = {Sequence motif finder using memetic algorithm.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {4}, pmid = {29298679}, issn = {1471-2105}, support = {458598/2014-3//Conselho Nacional de Desenvolvimento Científico e Tecnológico/International ; }, mesh = {*Algorithms ; Base Sequence ; Binding Sites ; Internet ; Transcription Factors/chemistry/genetics/*metabolism ; User-Computer Interface ; }, abstract = {BACKGROUND: De novo prediction of Transcription Factor Binding Sites (TFBS) using computational methods is a difficult task and it is an important problem in Bioinformatics. The correct recognition of TFBS plays an important role in understanding the mechanisms of gene regulation and helps to develop new drugs.

RESULTS: We here present Memetic Framework for Motif Discovery (MFMD), an algorithm that uses semi-greedy constructive heuristics as a local optimizer. In addition, we used a hybridization of the classic genetic algorithm as a global optimizer to refine the solutions initially found. MFMD can find and classify overrepresented patterns in DNA sequences and predict their respective initial positions. MFMD performance was assessed using ChIP-seq data retrieved from the JASPAR site, promoter sequences extracted from the ABS site, and artificially generated synthetic data. The MFMD was evaluated and compared with well-known approaches in the literature, called MEME and Gibbs Motif Sampler, achieving a higher f-score in the most datasets used in this work.

CONCLUSIONS: We have developed an approach for detecting motifs in biopolymers sequences. MFMD is a freely available software that can be promising as an alternative to the development of new tools for de novo motif discovery. Its open-source software can be downloaded at https://github.com/jadermcg/mfmd .}, } @article {pmid29298677, year = {2018}, author = {Gámez, G and Castro, A and Gómez-Mejia, A and Gallego, M and Bedoya, A and Camargo, M and Hammerschmidt, S}, title = {The variome of pneumococcal virulence factors and regulators.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {10}, pmid = {29298677}, issn = {1471-2164}, support = {CIEMB-097-13//Committee for Development of Research (CODI)/International ; }, mesh = {Bacterial Proteins/genetics ; Chromosome Mapping ; Genes, Bacterial ; Genes, Regulator ; *Genetic Variation ; Genome, Bacterial ; Phylogeny ; Streptococcus pneumoniae/classification/*genetics/pathogenicity ; Virulence Factors/*genetics ; }, abstract = {BACKGROUND: In recent years, the idea of a highly immunogenic protein-based vaccine to combat Streptococcus pneumoniae and its severe invasive infectious diseases has gained considerable interest. However, the target proteins to be included in a vaccine formulation have to accomplish several genetic and immunological characteristics, (such as conservation, distribution, immunogenicity and protective effect), in order to ensure its suitability and effectiveness. This study aimed to get comprehensive insights into the genomic organization, population distribution and genetic conservation of all pneumococcal surface-exposed proteins, genetic regulators and other virulence factors, whose important function and role in pathogenesis has been demonstrated or hypothesized.

RESULTS: After retrieving the complete set of DNA and protein sequences reported in the databases GenBank, KEGG, VFDB, P2CS and Uniprot for pneumococcal strains whose genomes have been fully sequenced and annotated, a comprehensive bioinformatic analysis and systematic comparison has been performed for each virulence factor, stand-alone regulator and two-component regulatory system (TCS) encoded in the pan-genome of S. pneumoniae. A total of 25 S. pneumoniae strains, representing different pneumococcal phylogenetic lineages and serotypes, were considered. A set of 92 different genes and proteins were identified, classified and studied to construct a pan-genomic variability map (variome) for S. pneumoniae. Both, pneumococcal virulence factors and regulatory genes, were well-distributed in the pneumococcal genome and exhibited a conserved feature of genome organization, where replication and transcription are co-oriented. The analysis of the population distribution for each gene and protein showed that 49 of them are part of the core genome in pneumococci, while 43 belong to the accessory-genome. Estimating the genetic variability revealed that pneumolysin, enolase and Usp45 (SP_2216 in S. p. TIGR4) are the pneumococcal virulence factors with the highest conservation, while TCS08, TCS05, and TCS02 represent the most conserved pneumococcal genetic regulators.

CONCLUSIONS: The results identified well-distributed and highly conserved pneumococcal virulence factors as well as regulators, representing promising candidates for a new generation of serotype-independent protein-based vaccine(s) to combat pneumococcal infections.}, } @article {pmid29298676, year = {2018}, author = {Obudulu, O and Mähler, N and Skotare, T and Bygdell, J and Abreu, IN and Ahnlund, M and Latha Gandla, M and Petterle, A and Moritz, T and Hvidsten, TR and Jönsson, LJ and Wingsle, G and Trygg, J and Tuominen, H}, title = {A multi-omics approach reveals function of Secretory Carrier-Associated Membrane Proteins in wood formation of​ ​​Populus​​ ​trees.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {11}, pmid = {29298676}, issn = {1471-2164}, support = {232-2009-1698//Svenska Forskningsrådet Formas/International ; RBP14-0011//Stiftelsen för Strategisk Forskning/International ; 2015-02290//VINNOVA (SE)/International ; SMK-1443//Kempestiftelserna/International ; }, mesh = {Biosynthetic Pathways/genetics ; Cell Wall/metabolism ; Gene Expression Profiling ; Membrane Proteins/genetics/metabolism/*physiology ; Metabolome ; Metabolomics ; Monosaccharides/metabolism ; Multigene Family ; Phenols/metabolism ; Plant Proteins/genetics/metabolism/*physiology ; Populus/*genetics/*metabolism ; Proteomics ; Trees ; Wood/genetics/*metabolism ; Xylem/metabolism ; }, abstract = {BACKGROUND: Secretory Carrier-Associated Membrane Proteins (SCAMPs) are highly conserved 32-38 kDa proteins that are involved in membrane trafficking. A systems approach was taken to elucidate function of SCAMPs in wood formation of Populus trees. Phenotypic and multi-omics analyses were performed in woody tissues of transgenic Populus trees carrying an RNAi construct for Populus tremula x tremuloides SCAMP3 (PttSCAMP3; Potri.019G104000).

RESULTS: The woody tissues of the transgenic trees displayed increased amounts of both polysaccharides and lignin oligomers, indicating increased deposition of both the carbohydrate and lignin components of the secondary cell walls. This coincided with a tendency towards increased wood density as well as significantly increased thickness of the suberized cork in the transgenic lines. Multivariate OnPLS (orthogonal projections to latent structures) modeling of five different omics datasets (the transcriptome, proteome, GC-MS metabolome, LC-MS metabolome and pyrolysis-GC/MS metabolome) collected from the secondary xylem tissues of the stem revealed systemic variation in the different variables in the transgenic lines, including changes that correlated with the changes in the secondary cell wall composition. The OnPLS model also identified a rather large number of proteins that were more abundant in the transgenic lines than in the wild type. Several of these were related to secretion and/or endocytosis as well as both primary and secondary cell wall biosynthesis.

CONCLUSIONS: Populus SCAMP proteins were shown to influence accumulation of secondary cell wall components, including polysaccharides and phenolic compounds, in the woody tissues of Populus tree stems. Our multi-omics analyses combined with the OnPLS modelling suggest that this function is mediated by changes in membrane trafficking to fine-tune the abundance of cell wall precursors and/or proteins involved in cell wall biosynthesis and transport. The data provides a multi-level source of information for future studies on the function of the SCAMP proteins in plant stem tissues.}, } @article {pmid29298675, year = {2018}, author = {Mizuno, H and Kasuga, S and Kawahigashi, H}, title = {Root lodging is a physical stress that changes gene expression from sucrose accumulation to degradation in sorghum.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {2}, pmid = {29298675}, issn = {1471-2229}, mesh = {*Gene Expression ; Plant Proteins/*genetics/metabolism ; Plant Roots/*physiology ; Plant Stems/*metabolism ; Sorghum/genetics/*physiology ; Stress, Physiological ; Sucrose/*metabolism ; }, abstract = {BACKGROUND: Sorghum (Sorghum bicolor L.) is used as a raw material for biofuels because it accumulates sugars at high levels in the stem. Lodging of sorghum occurs when the soil is wet and very high winds blow across the field. In root lodging, the roots are pulled loose from the soil, causing the plant to fall over. Lodging reduces the yield of nonstructural carbohydrates. It is not yet clear which genes show changes in expression when sorghum falls over. We compared whole-gene expression in the mature stems of intact and lodged sorghum plants, with a focus on comparisons from the perspective of differences in sugar accumulation or degradation.

RESULTS: Lodging decreased sucrose content, starch content, and ratio of sucrose to total sugars in the stems of the sorghum cultivar SIL-05. Particular paralogs of SWEET and TMT family genes, which encode sucrose or hexose transporters, or both, were significantly highly expressed in intact or lodged sorghum stems. In intact stems, genes encoding the glucose-6-phosphate translocator, aquaporins, and enzymes involved in photosynthesis and starch synthesis were highly expressed. In lodged sorghum stems, expression of genes associated with sucrose or starch degradation or energy production was increased. Notably, expression of genes encoding enzymes catalyzing irreversible reactions and associated with the first steps of these metabolic pathways (e.g. INV, SUS, and hexokinase- and fructokinase-encoding genes) was significantly increased by lodging. Expression of SUT, SPS, and SPP was almost the same in intact and lodged sorghum.

CONCLUSIONS: Specific paralogs of sucrose-associated genes involved in metabolic pathways and in membrane transport were expressed in the stems of sorghum SIL-05 at the full-ripe stage. Root lodging drastically changed the expression of these genes from sucrose accumulation to degradation. The changes in gene expression resulted in decreases in sugar content and in the proportion of sucrose to hexoses in the stems of lodged plants.}, } @article {pmid29298673, year = {2018}, author = {Fogelqvist, J and Tzelepis, G and Bejai, S and Ilbäck, J and Schwelm, A and Dixelius, C}, title = {Analysis of the hybrid genomes of two field isolates of the soil-borne fungal species Verticillium longisporum.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {14}, pmid = {29298673}, issn = {1471-2164}, mesh = {Carbohydrate Metabolism ; Evolution, Molecular ; Fungal Proteins/genetics ; Genes, Mating Type, Fungal ; *Genome, Fungal ; Phylogeny ; Polymorphism, Single Nucleotide ; Soil Microbiology ; Verticillium/classification/enzymology/*genetics/isolation & purification ; }, abstract = {BACKGROUND: Brassica plant species are attacked by a number of pathogens; among them, the ones with a soil-borne lifestyle have become increasingly important. Verticillium stem stripe caused by Verticillium longisporum is one example. This fungal species is thought to be of a hybrid origin, having a genome composed of combinations of lineages denominated A and D. In this study we report the draft genomes of 2 V. longisporum field isolates sequenced using the Illumina technology. Genomic characterization and lineage composition, followed by selected gene analysis to facilitate the comprehension of its genomic features and potential effector categories were performed.

RESULTS: The draft genomes of 2 Verticillium longisporum single spore isolates (VL1 and VL2) have an estimated ungapped size of about 70 Mb. The total number of protein encoding genes identified in VL1 was 20,793, whereas 21,072 gene models were predicted in VL2. The predicted genome size, gene contents, including the gene families coding for carbohydrate active enzymes were almost double the numbers found in V. dahliae and V. albo-atrum. Single nucleotide polymorphisms (SNPs) were frequently distributed in the two genomes but the distribution of heterozygosity and depth was not independent. Further analysis of potential parental lineages suggests that the V. longisporum genome is composed of two parts, A1 and D1, where A1 is more ancient than the parental lineage genome D1, the latter being more closer related to V. dahliae. Presence of the mating-type genes MAT1-1-1 and MAT1-2-1 in the V. longisporum genomes were confirmed. However, the MAT genes in V. dahliae, V. albo-atrum and V. longisporum have experienced extensive nucleotide changes at least partly explaining the present asexual nature of these fungal species.

CONCLUSIONS: The established draft genome of V. longisporum is comparatively large compared to other studied ascomycete fungi. Consequently, high numbers of genes were predicted in the two V. longisporum genomes, among them many secreted proteins and carbohydrate active enzyme (CAZy) encoding genes. The genome is composed of two parts, where one lineage is more ancient than the part being more closely related to V. dahliae. Dissimilar mating-type sequences were identified indicating possible ancient hybridization events.}, } @article {pmid29298672, year = {2018}, author = {Papadimitriou, ID and Lockey, SJ and Voisin, S and Herbert, AJ and Garton, F and Houweling, PJ and Cieszczyk, P and Maciejewska-Skrendo, A and Sawczuk, M and Massidda, M and Calò, CM and Astratenkova, IV and Kouvatsi, A and Druzhevskaya, AM and Jacques, M and Ahmetov, II and Stebbings, GK and Heffernan, S and Day, SH and Erskine, R and Pedlar, C and Kipps, C and North, KN and Williams, AG and Eynon, N}, title = {No association between ACTN3 R577X and ACE I/D polymorphisms and endurance running times in 698 Caucasian athletes.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {13}, pmid = {29298672}, issn = {1471-2164}, mesh = {Actinin/*genetics ; *Athletes ; European Continental Ancestry Group/genetics ; Female ; Genotype ; Humans ; Male ; Peptidyl-Dipeptidase A/*genetics ; Physical Endurance/*genetics ; *Polymorphism, Genetic ; Running/*physiology ; }, abstract = {BACKGROUND: Studies investigating associations between ACTN3 R577X and ACE I/D genotypes and endurance athletic status have been limited by small sample sizes from mixed sport disciplines and lack quantitative measures of performance.

AIM: To examine the association between ACTN3 R577X and ACE I/D genotypes and best personal running times in a large homogeneous cohort of endurance runners.

METHODS: We collected a total of 1064 personal best 1500, 3000, 5000 m and marathon running times of 698 male and female Caucasian endurance athletes from six countries (Australia, Greece, Italy, Poland, Russia and UK). Athletes were genotyped for ACTN3 R577X and ACE ID variants.

RESULTS: There was no association between ACTN3 R577X or ACE I/D genotype and running performance at any distance in men or women. Mean (SD) marathon times (in s) were for men: ACTN3 RR 9149 (593), RX 9221 (582), XX 9129 (582) p = 0.94; ACE DD 9182 (665), ID 9214 (549), II 9155 (492) p = 0.85; for women: ACTN3 RR 10796 (818), RX 10667 (695), XX 10675 (553) p = 0.36; ACE DD 10604 (561), ID 10766 (740), II 10771 (708) p = 0.21. Furthermore, there were no associations between these variants and running time for any distance in a sub-analysis of athletes with personal records within 20% of world records.

CONCLUSIONS: Thus, consistent with most case-control studies, this multi-cohort quantitative analysis demonstrates it is unlikely that ACTN3 XX genotype provides an advantage in competitive endurance running performance. For ACE II genotype, some prior studies show an association but others do not. Our data indicate it is also unlikely that ACE II genotype provides an advantage in endurance running.}, } @article {pmid29298668, year = {2018}, author = {Chen, CS and Chen, CY and Ravinath, DM and Bungahot, A and Cheng, CP and You, RI}, title = {Functional characterization of chitin-binding lectin from Solanum integrifolium containing anti-fungal and insecticidal activities.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {3}, pmid = {29298668}, issn = {1471-2229}, support = {TCMMP104-03 and TCIRP101005//Buddhist Tzu Chi Medical Foundation/International ; }, mesh = {Amino Acid Sequence ; Animals ; Base Sequence ; Chitin/metabolism ; Chromatography, Ion Exchange ; Colletotrichum/*drug effects ; Fungicides, Industrial/*pharmacology ; Insecticides/*pharmacology ; Larva/growth & development/physiology ; Plant Lectins/*genetics/metabolism ; Rhizoctonia/*drug effects ; Solanum/*genetics/metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization ; Spodoptera/*drug effects/growth & development ; }, abstract = {BACKGROUND: Along with the rapid development of glycomic tools, the study of lectin-carbohydrate interactions has expanded, opening the way for applications in the fields of analytic, diagnostic, and drug delivery. Chitin-binding lectins (CBLs) play roles in immune defense against chitin-containing pathogens. CBLs from species of the Solanaceae family, such as tomato, potato and jimsonweed, display different binding specificities to sugar chains containing poly-N-acetyllactosamine.

RESULTS: In this report, CBLs from Solanum integrifolium were isolated by ion exchange chromatography. The fractions showed hemagglutination activity (HA). The recombinant CBL in the 293F cell culture supernatant was able to inhibit the growth of Rhizoctonia solani and Colletotrichum gloeosporioide. Furthermore, the carbohydrate-binding property of CBLs was confirmed with the inhibition of HA. Binding of CBL to Spodoptera frugiperda (sf21) insect cells can partly be inhibited by N-Acetylglucosamine (GlcNAc), which is related to decrease mitochondrial membrane potential of sf21 cells.

CONCLUSIONS: The results showed that CBL exhibited antifungal properties and inhibited insect cell growth, which is directly correlated to the lectin-carbohydrate interaction. Further identification and characterization of CBLs will help to broaden their scope of application in plant defense and in biomedical applications.}, } @article {pmid29298667, year = {2018}, author = {Batayeva, D and Labaco, B and Ye, C and Li, X and Usenbekov, B and Rysbekova, A and Dyuskalieva, G and Vergara, G and Reinke, R and Leung, H}, title = {Genome-wide association study of seedling stage salinity tolerance in temperate japonica rice germplasm.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {2}, pmid = {29298667}, issn = {1471-2156}, mesh = {*Genome-Wide Association Study ; Oryza/classification/*genetics/physiology ; Polymorphism, Single Nucleotide ; Potassium/analysis ; Quantitative Trait Loci ; *Salt Tolerance ; Seedlings/genetics/physiology ; Sodium/analysis ; }, abstract = {BACKGROUND: Salinity has a significant impact on rice production in coastal, arid and semi-arid areas in many countries, including countries growing temperate rice, such as Kazakhstan. Recently, the complete genomes of 3000 rice accessions were sequenced through the 3 K rice genome project, and this set included 203 temperate japonica rice accessions. To identify salinity-tolerant germplasm and related genes for developing new salinity-tolerant breeding lines for the temperate japonica rice growing regions, we evaluated the seedling stage salinity tolerance of these sequenced temperate japonica rice accessions, and conducted genome-wide association studies (GWAS) for a series of salinity tolerance related traits.

RESULTS: There were 27 accessions performed well (SES < 5.0) under moderate salinity stress (EC12), and 5 accessions were tolerant under both EC12 and EC18. A total of 26 QTLs were identified for 9 measured traits. Eleven of these QTLs were co-located with known salinity tolerance genes. QTL/gene clusters were observed on chromosome 1, 2, 3, 6, 8 and 9. Six candidate genes were identified for five promising QTLs. The alleles of major QTL Saltol and gene O S HKT1;5 (SKC1) for Na+/K+ ratio identified in indica rice accessions were different from those in the temperate japonica rice accessions used in this study.

CONCLUSION: Salinity tolerant temperate japonica rice accessions were identified in this study, these accessions are important resources for breeding programs. SNPs located in the promising QTLs and candidate genes could be used for future gene validation and marker assisted selection. This study provided useful information for future studies on genetics and breeding of salinity tolerance in temperate japonica rice.}, } @article {pmid29298666, year = {2018}, author = {Guo, P and Zhu, B and Niu, H and Wang, Z and Liang, Y and Chen, Y and Zhang, L and Ni, H and Guo, Y and Hay, EHA and Gao, X and Gao, H and Wu, X and Xu, L and Li, J}, title = {Fast genomic prediction of breeding values using parallel Markov chain Monte Carlo with convergence diagnosis.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {3}, pmid = {29298666}, issn = {1471-2105}, mesh = {Animals ; Bayes Theorem ; Cattle ; China ; *Genome ; Markov Chains ; *Models, Genetic ; Monte Carlo Method ; Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: Running multiple-chain Markov Chain Monte Carlo (MCMC) provides an efficient parallel computing method for complex Bayesian models, although the efficiency of the approach critically depends on the length of the non-parallelizable burn-in period, for which all simulated data are discarded. In practice, this burn-in period is set arbitrarily and often leads to the performance of far more iterations than required. In addition, the accuracy of genomic predictions does not improve after the MCMC reaches equilibrium.

RESULTS: Automatic tuning of the burn-in length for running multiple-chain MCMC was proposed in the context of genomic predictions using BayesA and BayesCπ models. The performance of parallel computing versus sequential computing and tunable burn-in MCMC versus fixed burn-in MCMC was assessed using simulation data sets as well by applying these methods to genomic predictions of a Chinese Simmental beef cattle population. The results showed that tunable burn-in parallel MCMC had greater speedups than fixed burn-in parallel MCMC, and both had greater speedups relative to sequential (single-chain) MCMC. Nevertheless, genomic estimated breeding values (GEBVs) and genomic prediction accuracies were highly comparable between the various computing approaches. When applied to the genomic predictions of four quantitative traits in a Chinese Simmental population of 1217 beef cattle genotyped by an Illumina Bovine 770 K SNP BeadChip, tunable burn-in multiple-chain BayesCπ (TBM-BayesCπ) outperformed tunable burn-in multiple-chain BayesCπ (TBM-BayesA) and Genomic Best Linear Unbiased Prediction (GBLUP) in terms of the prediction accuracy, although the differences were not necessarily caused by computational factors and could have been intrinsic to the statistical models per se.

CONCLUSIONS: Automatically tunable burn-in multiple-chain MCMC provides an accurate and cost-effective tool for high-performance computing of Bayesian genomic prediction models, and this algorithm is generally applicable to high-performance computing of any complex Bayesian statistical model.}, } @article {pmid29298661, year = {2018}, author = {Wang, Z and Sun, L and Guan, W and Zhou, C and Tang, B and Cheng, Y and Huang, J and Xuan, F}, title = {De novo transcriptome sequencing and analysis of male and female swimming crab (Portunus trituberculatus) reproductive systems during mating embrace (stage II).}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {3}, pmid = {29298661}, issn = {1471-2156}, mesh = {Animals ; Brachyura/*genetics/growth & development/*physiology ; Female ; *Gene Expression Profiling ; Male ; Reproduction ; Sex Characteristics ; Sexual Maturation ; *Transcriptome ; }, abstract = {BACKGROUND: The swimming crab Portunus trituberculatus is one of the most commonly farmed crustaceans in China. As one of the most widely known and high-value edible crabs, it crab supports large crab fishery and aquaculture in China. Only large and sexually mature crabs can provide the greatest economic benefits, suggesting the considerable effect of reproductive system development on fishery. Studies are rarely conducted on the molecular regulatory mechanism underlying the development of the reproductive system during the mating embrace stage in this species. In this study, we used high-throughput sequencing to sequence all transcriptomes of the P. trituberculatus reproductive system.

RESULTS: Transcriptome sequencing of the reproductive system produced 81,688,878 raw reads (38,801,152 and 42,887,726 reads from female and male crabs, respectively). Low-quality (quality <20) reads were trimmed and removed, leaving only high-quality reads (37,020,664 and 41,021,030 from female and male crabs, respectively). A total of 126,188 (female) and 164,616 (male) transcripts were then generated by de novo transcriptome assembly using Trinity. Functional annotation of the obtained unigenes revealed that a large number of key genes and some important pathways may participate in cell proliferation and signal transduction. On the basis of our transcriptome analyses and as confirmed by quantitative real-time PCR, a number of genes potentially involved in the regulation of gonadal development and reproduction of P. trituberculatus were identified: ADRA1B, BAP1, ARL3, and TRPA1.

CONCLUSION: This study is the first to report on the whole reproductive system transcriptome information in stage II of P. trituberculatus gonadal development and provides rich resources for further studies to elucidate the molecular basis of the development of reproductive systems and reproduction in crabs. The current study can be used to further investigate functional genomics in this species.}, } @article {pmid29298288, year = {2018}, author = {Carrelha, J and Meng, Y and Kettyle, LM and Luis, TC and Norfo, R and Alcolea, V and Boukarabila, H and Grasso, F and Gambardella, A and Grover, A and Högstrand, K and Lord, AM and Sanjuan-Pla, A and Woll, PS and Nerlov, C and Jacobsen, SEW}, title = {Hierarchically related lineage-restricted fates of multipotent haematopoietic stem cells.}, journal = {Nature}, volume = {554}, number = {7690}, pages = {106-111}, doi = {10.1038/nature25455}, pmid = {29298288}, issn = {1476-4687}, support = {G0701761//Medical Research Council/United Kingdom ; G0801073//Medical Research Council/United Kingdom ; MC_UU_12009/5//Medical Research Council/United Kingdom ; G0501838//Medical Research Council/United Kingdom ; MC_UU_12009/7//Medical Research Council/United Kingdom ; G0900892//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Antigens, CD34 ; B-Lymphocytes/cytology ; Blood Platelets/cytology ; CD48 Antigen/deficiency ; *Cell Lineage ; Cell Self Renewal ; Erythroid Cells/cytology ; Female ; *Hematopoiesis ; Hematopoietic Stem Cells/*cytology/metabolism ; Male ; Megakaryocytes/cytology ; Mice ; Multipotent Stem Cells/*cytology/metabolism ; Myeloid Cells/cytology ; Signaling Lymphocytic Activation Molecule Family Member 1/metabolism ; T-Lymphocytes/cytology ; }, abstract = {Rare multipotent haematopoietic stem cells (HSCs) in adult bone marrow with extensive self-renewal potential can efficiently replenish all myeloid and lymphoid blood cells, securing long-term multilineage reconstitution after physiological and clinical challenges such as chemotherapy and haematopoietic transplantations. HSC transplantation remains the only curative treatment for many haematological malignancies, but inefficient blood-lineage replenishment remains a major cause of morbidity and mortality. Single-cell transplantation has uncovered considerable heterogeneity among reconstituting HSCs, a finding that is supported by studies of unperturbed haematopoiesis and may reflect different propensities for lineage-fate decisions by distinct myeloid-, lymphoid- and platelet-biased HSCs. Other studies suggested that such lineage bias might reflect generation of unipotent or oligopotent self-renewing progenitors within the phenotypic HSC compartment, and implicated uncoupling of the defining HSC properties of self-renewal and multipotency. Here we use highly sensitive tracking of progenitors and mature cells of the megakaryocyte/platelet, erythroid, myeloid and B and T cell lineages, produced from singly transplanted HSCs, to reveal a highly organized, predictable and stable framework for lineage-restricted fates of long-term self-renewing HSCs. Most notably, a distinct class of HSCs adopts a fate towards effective and stable replenishment of a megakaryocyte/platelet-lineage tree but not of other blood cell lineages, despite sustained multipotency. No HSCs contribute exclusively to any other single blood-cell lineage. Single multipotent HSCs can also fully restrict towards simultaneous replenishment of megakaryocyte, erythroid and myeloid lineages without executing their sustained lymphoid lineage potential. Genetic lineage-tracing analysis also provides evidence for an important role of platelet-biased HSCs in unperturbed adult haematopoiesis. These findings uncover a limited repertoire of distinct HSC subsets, defined by a predictable and hierarchical propensity to adopt a fate towards replenishment of a restricted set of blood lineages, before loss of self-renewal and multipotency.}, } @article {pmid29298140, year = {2018}, author = {Pethybridge, HR and Choy, CA and Polovina, JJ and Fulton, EA}, title = {Improving Marine Ecosystem Models with Biochemical Tracers.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {199-228}, doi = {10.1146/annurev-marine-121916-063256}, pmid = {29298140}, issn = {1941-0611}, abstract = {Empirical data on food web dynamics and predator-prey interactions underpin ecosystem models, which are increasingly used to support strategic management of marine resources. These data have traditionally derived from stomach content analysis, but new and complementary forms of ecological data are increasingly available from biochemical tracer techniques. Extensive opportunities exist to improve the empirical robustness of ecosystem models through the incorporation of biochemical tracer data and derived indices, an area that is rapidly expanding because of advances in analytical developments and sophisticated statistical techniques. Here, we explore the trophic information required by ecosystem model frameworks (species, individual, and size based) and match them to the most commonly used biochemical tracers (bulk tissue and compound-specific stable isotopes, fatty acids, and trace elements). Key quantitative parameters derived from biochemical tracers include estimates of diet composition, niche width, and trophic position. Biochemical tracers also provide powerful insight into the spatial and temporal variability of food web structure and the characterization of dominant basal and microbial food web groups. A major challenge in incorporating biochemical tracer data into ecosystem models is scale and data type mismatches, which can be overcome with greater knowledge exchange and numerical approaches that transform, integrate, and visualize data.}, } @article {pmid29298139, year = {2018}, author = {Trowbridge, JH and Lentz, SJ}, title = {The Bottom Boundary Layer.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {397-420}, doi = {10.1146/annurev-marine-121916-063351}, pmid = {29298139}, issn = {1941-0611}, abstract = {The oceanic bottom boundary layer extracts energy and momentum from the overlying flow, mediates the fate of near-bottom substances, and generates bedforms that retard the flow and affect benthic processes. The bottom boundary layer is forced by winds, waves, tides, and buoyancy and is influenced by surface waves, internal waves, and stratification by heat, salt, and suspended sediments. This review focuses on the coastal ocean. The main points are that (a) classical turbulence concepts and modern turbulence parameterizations provide accurate representations of the structure and turbulent fluxes under conditions in which the underlying assumptions hold, (b) modern sensors and analyses enable high-quality direct or near-direct measurements of the turbulent fluxes and dissipation rates, and}, } @article {pmid29298138, year = {2018}, author = {Balch, WM}, title = {The Ecology, Biogeochemistry, and Optical Properties of Coccolithophores.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {71-98}, doi = {10.1146/annurev-marine-121916-063319}, pmid = {29298138}, issn = {1941-0611}, abstract = {Coccolithophores are major contributors to phytoplankton communities and ocean biogeochemistry and are strong modulators of the optical field in the sea. New discoveries are changing paradigms about these calcifiers. A new role for silicon in coccolithophore calcification is coupling carbonate and silicon cycles. Phosphorus and iron play key roles in regulating coccolithophore growth. Comparing molecular phylogenies with coccolith morphometrics is forcing the reconciliation of biological and geological observations. Mixotrophy may be a possible life strategy for deep-dwelling species, which has ramifications for biological pump and alkalinity pump paradigms. Climate, ocean temperatures, and pH appear to be affecting coccolithophores in unexpected ways. Global calcification is approximately 1-3% of primary productivity and affects CO2 budgets. New measurements of the backscattering cross section of coccolithophores have improved satellite-based algorithms and their application in case I and case II optical waters. Remote sensing has allowed the detection of basin-scale coccolithophore features in the Southern Ocean.}, } @article {pmid29298137, year = {2018}, author = {Beaugrand, G and Kirby, RR}, title = {How Do Marine Pelagic Species Respond to Climate Change? Theories and Observations.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {169-197}, doi = {10.1146/annurev-marine-121916-063304}, pmid = {29298137}, issn = {1941-0611}, abstract = {In this review, we show how climate affects species, communities, and ecosystems, and why many responses from the species to the biome level originate from the interaction between the species' ecological niche and changes in the environmental regime in both space and time. We describe a theory that allows us to understand and predict how marine species react to climate-induced changes in ecological conditions, how communities form and are reconfigured, and so how biodiversity is arranged and may respond to climate change. Our study shows that the responses of species to climate change are therefore intelligible-that is, they have a strong deterministic component and can be predicted.}, } @article {pmid29298136, year = {2018}, author = {Dugdale, RC}, title = {A Biogeochemical Oceanographer at Sea: My Life with Nitrogen and a Nod to Silica.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {1-18}, doi = {10.1146/annurev-marine-121916-063655}, pmid = {29298136}, issn = {1941-0611}, abstract = {My evolution from electrical engineering student to limnologist and then to oceanographer was a consequence of generous mentoring, which led to my use of the 15N tracer technique to measure nitrogen fixation in aquatic systems. The concept of new and regenerated production arose when I applied this method to measure nitrate and ammonium uptake in marine ecosystems. I then showed that enzyme kinetics could be applied to algal nitrogen uptake and used a silicate pump to explain silicate limitation of diatoms in coastal and equatorial upwelling systems. These concepts are now recognized as modern nutrient paradigms in biogeochemical oceanography. My interest in nutrients required field studies and led to my passion for the study of upwelling ecosystems and the establishment of two major international programs, with numerous advisors, collaborators, and students helping along the way.}, } @article {pmid29298135, year = {2018}, author = {}, title = {Introduction.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {i}, doi = {10.1146/annurev-ma-10-112517-100001}, pmid = {29298135}, issn = {1941-0611}, } @article {pmid29298091, year = {2018}, author = {Marians, KJ}, title = {Lesion Bypass and the Reactivation of Stalled Replication Forks.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {217-238}, doi = {10.1146/annurev-biochem-062917-011921}, pmid = {29298091}, issn = {1545-4509}, abstract = {Accurate transmission of the genetic information requires complete duplication of the chromosomal DNA each cell division cycle. However, the idea that replication forks would form at origins of DNA replication and proceed without impairment to copy the chromosomes has proven naive. It is now clear that replication forks stall frequently as a result of encounters between the replication machinery and template damage, slow-moving or paused transcription complexes, unrelieved positive superhelical tension, covalent protein-DNA complexes, and as a result of cellular stress responses. These stalled forks are a major source of genome instability. The cell has developed many strategies for ensuring that these obstructions to DNA replication do not result in loss of genetic information, including DNA damage tolerance mechanisms such as lesion skipping, whereby the replisome jumps the lesion and continues downstream; template switching both behind template damage and at the stalled fork; and the error-prone pathway of translesion synthesis.}, } @article {pmid29297953, year = {2018}, author = {Citadini, JM and Brandt, R and Williams, CR and Gomes, FR}, title = {Evolution of morphology and locomotor performance in anurans: relationships with microhabitat diversification.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {371-381}, doi = {10.1111/jeb.13228}, pmid = {29297953}, issn = {1420-9101}, abstract = {The relationships between morphology, performance, behavior and ecology provide evidence for multiple and complex phenotypic adaptations. The anuran body plan, for example, is evolutionarily conserved and shows clear specializations to jumping performance back at least to the early Jurassic. However, there are instances of more recent adaptation to habit diversity in the post-cranial skeleton, including relative limb length. The present study tested adaptive models of morphological evolution in anurans associated with the diversity of microhabitat use (semi-aquatic arboreal, fossorial, torrent, and terrestrial) in species of anuran amphibians from Brazil and Australia. We use phylogenetic comparative methods to determine which evolutionary models, including Brownian motion (BM) and Ornstein-Uhlenbeck (OU) are consistent with morphological variation observed across anuran species. Furthermore, this study investigated the relationship of maximum distance jumped as a function of components of morphological variables and microhabitat use. We found there are multiple optima of limb lengths associated to different microhabitats with a trend of increasing hindlimbs in torrent, arboreal, semi-aquatic whereas fossorial and terrestrial species evolve toward optima with shorter hindlimbs. Moreover, arboreal, semi-aquatic and torrent anurans have higher jumping performance and longer hindlimbs, when compared to terrestrial and fossorial species. We corroborate the hypothesis that evolutionary modifications of overall limb morphology have been important in the diversification of locomotor performance along the anuran phylogeny. Such evolutionary changes converged in different phylogenetic groups adapted to similar microhabitat use in two different zoogeographical regions.}, } @article {pmid29297849, year = {2018}, author = {Chaudhary, DK and Kim, J}, title = {Tessaracoccus terricola sp. nov., isolated from oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {529-535}, doi = {10.1099/ijsem.0.002537}, pmid = {29297849}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nepal ; Nucleic Acid Hybridization ; *Petroleum Pollution ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Propionibacteriaceae/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Spermidine/chemistry ; Spermine/chemistry ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, non-motile, yellow and rod-shaped actinobacterium, designated strain Brt-AT, isolated from oil-contaminated soil, grew at 15-40 °C, at pH 5.5-10.0 and at 0-2 % (w/v) NaCl concentration. This strain was characterized by a polyphasic approach. The 16S rRNA gene sequence analysis showed that strain Brt-AT belonged to the genus Tessaracoccus and is closely related to Tessaracoccus rhinocerotis YIM 101269T, Tessaracoccus flavescens SST-39T, Tessaracoccus defluvii LNB-140T and Tessaracoccus flavus RP1T (99.03, 97.00, 96.88, and 96.46 % gene sequence similarity, respectively). The predominant respiratory quinone was MK-9(H4); the major polar lipids were phosphatidylglycerol and diphosphatidylglycerol; the predominant polyamines were spermine and spermidine; and the major fatty acids were anteiso-C15 : 0 and iso-C15 : 0. The cell-wall peptidoglycan contained ll-diaminopimelic acid; and glucose and ribose were detected as diagnostic sugars from whole-cell hydrolysates. The DNA G+C content was 68.1 mol%. The DNA-DNA relatedness between strain Brt-AT and its closely related species of the genus Tessaracoccus were between 55.0-44.0 %, which fall below the threshold value of 70 % for the strain to be considered as novel. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain Brt-AT represents a novel species of the genus Tessaracoccus, for which the name Tessaracoccus terricola sp. nov. is proposed. The type strain is Brt-AT (=KEMB 9005-690T=KACC 19391T=JCM 32157T).}, } @article {pmid29297848, year = {2018}, author = {Siddiqi, MZ and Choi, GM and Im, WT}, title = {Ciceribacter azotifigens sp. nov., a nitrogen-fixing bacterium isolated from activated sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {482-486}, doi = {10.1099/ijsem.0.002438}, pmid = {29297848}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Ginsenosides ; *Nitrogen Fixation ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhizobiaceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Sewage/*microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-reaction-negative, catalase- and oxidase-positive, aerobic, transparent, motile and rod-shaped bacterium that was capable of fixing dinitrogen (designated strain A.slu09T), isolated from activated sludge, was characterized by a polyphasic approach to clarify its taxonomic position. Strain A.slu09T was observed to grow optimally at 30 °C and at pH 7.0 on R2A agar medium. Strain A.slu09T showed β-glucosidase activity, converting the major ginsenoside Rd to ginsenoside F2. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain A.slu09T belongs to the genus Ciceribacter of the family Rhizobiaceae and was most closely related to Ciceribacter lividus MSSRFBL1T (97.8 % similarity). The DNA G+C content was 67.2 mol%. The DNA-DNA hybridization value between strain A.slu09T and C. lividus KCTC 32403T was 16.9±1.17 %. The major polar lipids were phosphatidylcholine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylmethylethanolamine, phosphatidylethanolamine, aminophospholipid and two glycolipids, and one unknown phospholipid as a minor lipid. The predominant quinone was ubiquinone-10 (Q-10). The major fatty acids were C19 : 0 cyclo ω8c, C18 : 1 ω7c and/or C18 : 1ω6c (summed feature 8) and C18 : 0, a profile that supported the affiliation of A.slu09T to the genus Ciceribacter. Moreover, the physiological and biochemical characteristics and low level of DNA-DNA relatedness allowed the phenotypic and genotypic differentiation of strain A.slu09T from the recognized species of the genus Ciceribacter. Therefore, strain A.slu09T represents a novel species of the genus Ciceribacter, for which the name Ciceribacter azotifigens sp. nov. is proposed. The type strain is A.slu09T (=KACC 19080T=LMG 29962T).}, } @article {pmid29297847, year = {2018}, author = {Yang, SH and Oh, JH and Seo, HS and Lee, JH and Kwon, KK}, title = {Marinirhabdus citrea sp. nov., a marine bacterium isolated from a seaweed.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {547-551}, doi = {10.1099/ijsem.0.002539}, pmid = {29297847}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seaweed/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A gram-stain-negative, aerobic, rod-shaped (1.3-1.9×0.3-0.5 µm) and non-motile marine bacterium, designated MEBiC09412T, was isolated from seaweed collected at Yeonggwang County, South Korea. 16S rRNA gene sequence analysis demonstrated that strain MEBiC09412T shared high sequence similarity with Marinirhabdus gelatinilytica NH83T (95.4 %). Growth was observed at 17-38 °C (optimum 30 °C), at pH 4.0-8.5 (optimum pH 7.0) and with 0.5-6.0 % (w/v; optimum 2.5 %) NaCl. The predominant cellular fatty acids were iso-C15 : 0 (27.4 %), iso-C15 : 1 G (9.6 %), anteiso-C15 : 0 (14.6 %), iso-C16 : 0 (6.2 %), iso-C17 : 0 3OH (13.2 %) and summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c; 7.4 %). The DNA G+C content was determined to be 43.1 mol%, while the major respiratory quinone was menaquinone-6. Several phenotypic characteristics such as indole production, the oxidizing patterns of several carbohydrtaes (of glucose, fructose, sucrose, maltose, mannose etc.) and organic acids, and the enzyme activities of α-chymotrypsin and α-glucosidase differentiated strain MEBiC09412T from M. gelatinilytica NH83T. On the basis of this polyphasic taxonomic data, strain MEBiC09412T should be classified as a novel species of the genus Marinirhabduswith the suggested name Marinirhabdus citrea sp. nov. The type strain is MEBiC09412T (=KCCM 43216T=JCM 31588T).}, } @article {pmid29297846, year = {2018}, author = {Zhang, YG and Zhou, XK and Guo, JW and Xiao, M and Wang, HF and Wang, Y and Bobodzhanova, K and Li, WJ}, title = {Bacillus tamaricis sp. nov., an alkaliphilic bacterium isolated from a Tamarix cone soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {558-563}, doi = {10.1099/ijsem.0.002543}, pmid = {29297846}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Tamaricaceae/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, alkaliphilic bacterium, designated EGI 80668T, was isolated from a Tamarix cone soil in Xinjiang, north-west China. Cells were facultatively anaerobic, terminal endospore-forming and motile by means of peritrichous flagella. Colonies were yellowish and the cells showed oxidase-negative and catalase-positive reactions. Strain EGI 80668T grew at pH 8.0-10.0 and with 0-10 % (w/v) NaCl (optimally at pH 9.0 and with 1-2 % NaCl) on marine agar 2216. The predominant menaquinone was MK-7. The major fatty acids were anteiso-C17 : 0 and anteiso-C15 : 0. The cellular polar lipids contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, four unknown phospholipids and one unknown aminophospholipid. The G+C content of the genomic DNA was 38.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain EGI 80668T was affiliated to the genus Bacillus. The highest 16S rRNA gene sequence similarity between strain EGI 80668T and a member of the genus Bacillus was 96.83 % with Bacillus cellulosilyticus JCM 9156T. A polyphasic taxonomic study based on morphological, physiological, biochemical and phylogenetic data indicated that strain EGI 80668T represents a novel species of the genus Bacillus, for which the name Bacillus tamaricis sp. nov. (type strain EGI 80668T=KCTC 33703T=CGMCC 1.15917T) is proposed.}, } @article {pmid29297845, year = {2018}, author = {Dai, H and Wang, Y and Fang, Y and Xiao, T and Huang, Z and Kan, B and Wang, D}, title = {Proteus columbae sp. nov., isolated from a pigeon in Ma'anshan, China.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {552-557}, doi = {10.1099/ijsem.0.002541}, pmid = {29297845}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; China ; Columbidae/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Nucleic Acid Hybridization ; *Phylogeny ; Proteus/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-negative, facultatively anaerobic bacillus, strain 08MAS2615T, was isolated from the flesh of a pigeon specimen collected in Ma'anshan, Anhui province, China. Phylogenetic analysis of 16S rRNA gene sequences confirmed that strain 08MAS2615T belonged to the genus Proteus, and formed an independent branch which was clearly separated from the other six known species of Proteus. Strain 08MAS2615T was more closely related to Proteus vulgaris ATCC 29905T and Proteus penneri NCTC 12737T than other Proteus species. Similar independent phylogenetic results were obtained using rpoB gene sequence analysis, whereas strain 08MAS2615T clustered near the species of Proteus cibarius JS9T and Proteus terrae N5/687T. Furthermore, the genome-wide core-single nucleotide polymorphism-based phylogenetic tree confirmed that strain 08MAS2615T formed a monophyletic and robust clade. Based on whole-genome sequences, the range of in silico DNA-DNA hybridization and average nucleotide identity between strain 08MAS2615T and the six Proteus species were 25.5-48.8 % and 82.8-92.9 %, respectively, less than the proposed cutoff level for species delineation, i.e. 70 and 95 %. In addition, the major cellular fatty acid profile of strain 08MAS2615T was C14 : 0 (12.4 %), C16 : 0 (23.8 %), C17 : 0cyclo (14.4 %), summed feature 2 (C16 : 1iso I/C14 : 0 3-OH) (11.0 %), summed feature 3 (C16 : 1ω7c/16 : 1ω6c) (18.5 %) and summed feature 8 (C18 : 1ω6c) (18.6 %). On the basis of these results, strain 08MAS2615T represents a novel species of the genus Proteus, for which the name Proteuscolumbae sp. nov. is proposed with strain 08MAS2615T (=DSM 104686T=CGMCC 1.15982T) designated as the species type strain.}, } @article {pmid29297095, year = {2018}, author = {Garstang, MG and Ferrier, DEK}, title = {Amphioxus SYCP1: a case of retrogene replacement and co-option of regulatory elements adjacent to the ParaHox cluster.}, journal = {Development genes and evolution}, volume = {228}, number = {1}, pages = {13-30}, pmid = {29297095}, issn = {1432-041X}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {5' Untranslated Regions ; Amino Acid Sequence ; Animals ; DNA-Binding Proteins/genetics ; *Evolution, Molecular ; Gene Expression Regulation, Developmental ; Gonads/metabolism ; Homeodomain Proteins/genetics ; Lancelets/classification/embryology/*genetics ; Nuclear Proteins/*genetics ; Phylogeny ; Promoter Regions, Genetic ; Sequence Alignment ; Synaptonemal Complex/chemistry/genetics ; }, abstract = {Retrogenes are formed when an mRNA is reverse-transcribed and reinserted into the genome in a location unrelated to the original locus. If this retrocopy inserts into a transcriptionally favourable locus and is able to carry out its original function, it can, in rare cases, lead to retrogene replacement. This involves the original, often multi-exonic, parental copy being lost whilst the newer single-exon retrogene copy 'replaces' the role of the ancestral parent gene. One example of this is amphioxus SYCP1, a gene that encodes a protein used in synaptonemal complex formation during meiosis and which offers the opportunity to examine how a retrogene evolves after the retrogene replacement event. SYCP1 genes exist as large multi-exonic genes in most animals. AmphiSYCP1, however, contains a single coding exon of ~ 3200 bp and has inserted next to the ParaHox cluster of amphioxus, whilst the multi-exonic ancestral parental copy has been lost. Here, we show that AmphiSYCP1 has not only replaced its parental copy, but also has evolved additional regulatory function by co-opting a bidirectional promoter from the nearby AmphiCHIC gene. AmphiSYCP1 has also evolved a de novo, multi-exonic 5'untranslated region that displays distinct regulatory states, in the form of two different isoforms, and has evolved novel expression patterns during amphioxus embryogenesis in addition to its ancestral role in meiosis. The absence of ParaHox-like expression of AmphiSYCP1, despite its proximity to the ParaHox cluster, also suggests that this gene is not influenced by any potential pan-cluster regulatory mechanisms, which are seemingly restricted to only the ParaHox genes themselves.}, } @article {pmid29295964, year = {2018}, author = {Beans, C}, title = {News Feature: Can microbes keep time for forensic investigators?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {3-6}, pmid = {29295964}, issn = {1091-6490}, mesh = {*Autopsy ; Forensic Medicine/*methods ; Humans ; *Microbiota ; }, } @article {pmid29295939, year = {2018}, author = {Tian, L and Kim, MS and Li, H and Wang, J and Yang, W}, title = {Structure of HIV-1 reverse transcriptase cleaving RNA in an RNA/DNA hybrid.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {507-512}, pmid = {29295939}, issn = {1091-6490}, support = {Z01 DK036144/DK/NIDDK NIH HHS/United States ; }, mesh = {Catalytic Domain ; Crystallography, X-Ray ; DNA, Viral/chemistry/*genetics/metabolism ; HIV Infections/virology ; HIV Reverse Transcriptase/*chemistry/genetics/*metabolism ; HIV-1/chemistry/*enzymology/genetics ; Humans ; Models, Molecular ; Nucleic Acid Conformation ; RNA, Viral/chemistry/*genetics/metabolism ; Ribonuclease H/chemistry/genetics/metabolism ; Substrate Specificity ; }, abstract = {HIV-1 reverse transcriptase (RT) contains both DNA polymerase and RNase H activities to convert the viral genomic RNA to dsDNA in infected host cells. Here we report the 2.65-Å resolution structure of HIV-1 RT engaging in cleaving RNA in an RNA/DNA hybrid. A preferred substrate sequence is absolutely required to enable the RNA/DNA hybrid to adopt the distorted conformation needed to interact properly with the RNase H active site in RT. Substituting two nucleotides 4 bp upstream from the cleavage site results in scissile-phosphate displacement by 4 Å. We also have determined the structure of HIV-1 RT complexed with an RNase H-resistant polypurine tract sequence, which adopts a rigid structure and is accommodated outside of the nuclease active site. Based on this newly gained structural information and a virtual drug screen, we have identified an inhibitor specific for the viral RNase H but not for its cellular homologs.}, } @article {pmid29295938, year = {2018}, author = {}, title = {Correction for Singh et al., Increasing potential for intense tropical and subtropical thunderstorms under global warming.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E342}, doi = {10.1073/pnas.1721679115}, pmid = {29295938}, issn = {1091-6490}, } @article {pmid29295937, year = {2018}, author = {Wang, C and Lu, X}, title = {Hamilton's inclusive fitness maintains heritable altruism polymorphism through rb = c.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {8}, pages = {1860-1864}, pmid = {29295937}, issn = {1091-6490}, mesh = {*Altruism ; Animals ; Behavior, Animal ; Birds/*genetics ; Female ; *Genetic Fitness ; Genotype ; Male ; *Models, Genetic ; *Polymorphism, Genetic ; Social Behavior ; }, abstract = {How can altruism evolve or be maintained in a selfish world? Hamilton's rule shows that the former process will occur when rb > c-the benefits to the recipients of an altruistic act b, weighted by the relatedness between the social partners r, exceed the costs to the altruists c-drives altruistic genotypes spreading against nonaltruistic ones. From this rule, we infer that altruistic genotypes will persist in a population by forming a stable heritable polymorphism with nonaltruistic genotypes if rb = c makes inclusive fitness of the two morphs equal. We test this prediction using the data of 12 years of study on a cooperatively breeding bird, the Tibetan ground tit Pseudopodoces humilis, where helping is performed by males only and kin-directed. Individual variation in ever acting as a helper was heritable (h2 = 0.47), and the resultant altruism polymorphism remained stable as indicated by low-level annual fluctuation of the percentage of helpers among all adult males (24-28%). Helpers' indirect fitness gains from increased lifetime reproductive success of related breeders statistically fully compensated for their lifetime direct fitness losses, suggesting that rb = c holds. While our work provides a fundamental support for Hamilton's idea, it highlights the equivalent inclusive fitness returns to altruists and nonaltruists mediated by rb = c as a theoretically and realistically important mechanism to maintain social polymorphism.}, } @article {pmid29295936, year = {2018}, author = {Lu, L and Zhu, F and Zhang, M and Li, Y and Drennan, AC and Kimpara, S and Rumball, I and Selzer, C and Cameron, H and Kellicut, A and Kelm, A and Wang, F and Waldmann, TA and Rui, L}, title = {Gene regulation and suppression of type I interferon signaling by STAT3 in diffuse large B cell lymphoma.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E498-E505}, pmid = {29295936}, issn = {1091-6490}, support = {KL2 TR000428/TR/NCATS NIH HHS/United States ; R01 CA187299/CA/NCI NIH HHS/United States ; T32 HL007899/HL/NHLBI NIH HHS/United States ; UL1 TR000427/TR/NCATS NIH HHS/United States ; }, mesh = {Cell Differentiation ; Cell Line, Tumor ; Cell Movement ; Cell Proliferation ; Cell Survival ; Cytokines/genetics/metabolism ; Gene Expression Regulation, Neoplastic/*drug effects ; Genome-Wide Association Study ; Humans ; Immunologic Factors/administration & dosage/pharmacology ; Interferon Type I/genetics/*metabolism ; Lenalidomide ; Lymphoma, Large B-Cell, Diffuse/*metabolism ; Pyrazoles/administration & dosage/*pharmacology ; STAT3 Transcription Factor/antagonists & inhibitors/genetics/*metabolism ; Signal Transduction/*physiology ; Thalidomide/administration & dosage/analogs & derivatives/pharmacology ; }, abstract = {STAT3 is constitutively activated in many cancers and regulates gene expression to promote cancer cell survival, proliferation, invasion, and migration. In diffuse large B cell lymphoma (DLBCL), activation of STAT3 and its kinase JAK1 is caused by autocrine production of IL-6 and IL-10 in the activated B cell-like subtype (ABC). However, the gene regulatory mechanisms underlying the pathogenesis of this aggressive lymphoma by STAT3 are not well characterized. Here we performed genome-wide analysis and identified 2,251 STAT3 direct target genes, which involve B cell activation, survival, proliferation, differentiation, and migration. Whole-transcriptome profiling revealed that STAT3 acts as both a transcriptional activator and a suppressor, with a comparable number of up- and down-regulated genes. STAT3 regulates multiple oncogenic signaling pathways, including NF-κB, a cell-cycle checkpoint, PI3K/AKT/mTORC1, and STAT3 itself. In addition, STAT3 negatively regulates the lethal type I IFN signaling pathway by inhibiting expression of IRF7, IRF9, STAT1, and STAT2 Inhibition of STAT3 activity by ruxolitinib synergizes with the type I IFN inducer lenalidomide in growth inhibition of ABC DLBCL cells in vitro and in a xenograft mouse model. Therefore, this study provides a mechanistic rationale for clinical trials to evaluate ruxolitinib or a specific JAK1 inhibitor combined with lenalidomide in ABC DLBCL.}, } @article {pmid29295935, year = {2018}, author = {Yang, YM and Sun, D and Kandhi, S and Froogh, G and Zhuge, J and Huang, W and Hammock, BD and Huang, A}, title = {Estrogen-dependent epigenetic regulation of soluble epoxide hydrolase via DNA methylation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {613-618}, pmid = {29295935}, issn = {1091-6490}, support = {P42 ES004699/ES/NIEHS NIH HHS/United States ; R01 ES002710/ES/NIEHS NIH HHS/United States ; R01 HL070653/HL/NHLBI NIH HHS/United States ; R01 HL129797/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; DNA Methylation ; *Epigenesis, Genetic ; Epoxide Hydrolases/*genetics/metabolism ; Estradiol/*metabolism ; Estrogens/*metabolism ; Female ; Gene Silencing ; HEK293 Cells ; Humans ; Male ; Mesenteric Arteries/metabolism ; Mice ; Promoter Regions, Genetic ; Receptors, Estrogen/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {To elucidate molecular mechanisms responsible for the sexually dimorphic phenotype of soluble epoxide hydrolase (sEH) expression, we tested the hypothesis that female-specific down-regulation of sEH expression is driven by estrogen-dependent methylation of the Ephx2 gene. Mesenteric arteries isolated from male, female, ovariectomized female (OV), and OV with estrogen replacement (OVE) mice, as well as the human cell line (HEK293T) were used. Methylation-specific PCR and bisulfite genomic sequencing analysis indicate significant increases in DNA/CG methylation in vessels of female and OVE compared with those of male and OV mice. The same increase in CG methylation was also observed in male vessels incubated with a physiological concentration of 17β-estradiol (17β-E2) for 48 hours. All vessels that displayed increases in CG methylation were concomitantly associated with decreases in their Ephx2 mRNA and protein, suggesting a methylation-induced gene silencing. Transient transfection assays indicate that the activity of Ephx2 promoter-coding luciferase was significantly attenuated in HEK293T cells treated with 17β-E2, which was prevented by additional treatment with an estrogen receptor antagonist (ICI). ChIP analysis indicates significantly reduced binding activities of transcription factors (including SP1, AP-1, and NF-κB with their binding elements located in the Ephx2 promoter) in vessels of female mice and human cells treated with 17β-E2, responses that were prevented by ICI and Decitabine (DNA methyltransferase inhibitor), respectively. In conclusion, estrogen/estrogen receptor-dependent methylation of the promoter of Ephx2 gene silences sEH expression, which is involved in specific transcription factor-directed regulatory pathways.}, } @article {pmid29295934, year = {2018}, author = {Kim, MC and Silberberg, YR and Abeyaratne, R and Kamm, RD and Asada, HH}, title = {Computational modeling of three-dimensional ECM-rigidity sensing to guide directed cell migration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E390-E399}, pmid = {29295934}, issn = {1091-6490}, mesh = {Biomechanical Phenomena ; Cell Adhesion ; Cell Movement/*physiology ; *Computer Simulation ; Cytoskeleton/physiology ; Elasticity ; Extracellular Matrix/*physiology ; Focal Adhesions ; *Models, Biological ; Pseudopodia ; }, abstract = {Filopodia have a key role in sensing both chemical and mechanical cues in surrounding extracellular matrix (ECM). However, quantitative understanding is still missing in the filopodial mechanosensing of local ECM stiffness, resulting from dynamic interactions between filopodia and the surrounding 3D ECM fibers. Here we present a method for characterizing the stiffness of ECM that is sensed by filopodia based on the theory of elasticity and discrete ECM fiber. We have applied this method to a filopodial mechanosensing model for predicting directed cell migration toward stiffer ECM. This model provides us with a distribution of force and displacement as well as their time rate of changes near the tip of a filopodium when it is bound to the surrounding ECM fibers. Aggregating these effects in each local region of 3D ECM, we express the local ECM stiffness sensed by the cell and explain polarity in the cellular durotaxis mechanism.}, } @article {pmid29295933, year = {2018}, author = {Farley, JE and Burdett, TC and Barria, R and Neukomm, LJ and Kenna, KP and Landers, JE and Freeman, MR}, title = {Transcription factor Pebbled/RREB1 regulates injury-induced axon degeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1358-1363}, pmid = {29295933}, issn = {1091-6490}, support = {R01 NS053538/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Armadillo Domain Proteins/genetics/metabolism ; Axons/metabolism/*pathology ; Cholinergic Neurons/pathology ; Cytoskeletal Proteins/genetics/metabolism ; DNA-Binding Proteins/genetics/metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster/genetics ; Nuclear Proteins/genetics/*metabolism ; Transcription Factors/genetics/*metabolism ; Wallerian Degeneration/genetics/metabolism/*pathology ; Wings, Animal/innervation/metabolism ; Zinc Fingers/genetics ; }, abstract = {Genetic studies of Wallerian degeneration have led to the identification of signaling molecules (e.g., dSarm/Sarm1, Axundead, and Highwire) that function locally in axons to drive degeneration. Here we identify a role for the Drosophila C2H2 zinc finger transcription factor Pebbled [Peb, Ras-responsive element binding protein 1 (RREB1) in mammals] in axon death. Loss of Peb in Drosophila glutamatergic sensory neurons results in either complete preservation of severed axons, or an axon death phenotype where axons fragment into large, continuous segments, rather than completely disintegrate. Peb is expressed in developing and mature sensory neurons, suggesting it is required to establish or maintain their competence to undergo axon death. peb mutant phenotypes can be rescued by human RREB1, and they exhibit dominant genetic interactions with dsarm mutants, linking peb/RREB1 to the axon death signaling cascade. Surprisingly, Peb is only able to fully block axon death signaling in glutamatergic, but not cholinergic sensory neurons, arguing for genetic diversity in axon death signaling programs in different neuronal subtypes. Our findings identify a transcription factor that regulates axon death signaling, and peb mutant phenotypes of partial fragmentation reveal a genetically accessible step in axon death signaling.}, } @article {pmid29295932, year = {2018}, author = {Khandekar, MJ and Banks, AS and Laznik-Bogoslavski, D and White, JP and Choi, JH and Kazak, L and Lo, JC and Cohen, P and Wong, KK and Kamenecka, TM and Griffin, PR and Spiegelman, BM}, title = {Noncanonical agonist PPARγ ligands modulate the response to DNA damage and sensitize cancer cells to cytotoxic chemotherapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {561-566}, pmid = {29295932}, issn = {1091-6490}, support = {R01 DK105825/DK/NIDDK NIH HHS/United States ; R01 DK107717/DK/NIDDK NIH HHS/United States ; C06 CA059267/CA/NCI NIH HHS/United States ; K08 DK097303/DK/NIDDK NIH HHS/United States ; P30 DK034854/DK/NIDDK NIH HHS/United States ; R37 DK031405/DK/NIDDK NIH HHS/United States ; R01 DK031405/DK/NIDDK NIH HHS/United States ; }, mesh = {Amino Acid Motifs ; Animals ; Antineoplastic Agents/*administration & dosage ; Apoptosis/drug effects ; Carboplatin/administration & dosage ; Cell Line, Tumor ; *DNA Damage/drug effects ; Humans ; Ligands ; Lung Neoplasms/*drug therapy/genetics/metabolism ; Male ; Mice ; Mice, Nude ; PPAR gamma/agonists/chemistry/genetics/*metabolism ; Phosphorylation ; Thiazolidinediones/*administration & dosage ; Tumor Suppressor Protein p53/genetics/metabolism ; }, abstract = {The peroxisome-proliferator receptor-γ (PPARγ) is expressed in multiple cancer types. Recently, our group has shown that PPARγ is phosphorylated on serine 273 (S273), which selectively modulates the transcriptional program controlled by this protein. PPARγ ligands, including thiazolidinediones (TZDs), block S273 phosphorylation. This activity is chemically separable from the canonical activation of the receptor by agonist ligands and, importantly, these noncanonical agonist ligands do not cause some of the known side effects of TZDs. Here, we show that phosphorylation of S273 of PPARγ occurs in cancer cells on exposure to DNA damaging agents. Blocking this phosphorylation genetically or pharmacologically increases accumulation of DNA damage, resulting in apoptotic cell death. A genetic signature of PPARγ phosphorylation is associated with worse outcomes in response to chemotherapy in human patients. Noncanonical agonist ligands sensitize lung cancer xenografts and genetically induced lung tumors to carboplatin therapy. Moreover, inhibition of this phosphorylation results in deregulation of p53 signaling, and biochemical studies show that PPARγ physically interacts with p53 in a manner dependent on S273 phosphorylation. These data implicate a role for PPARγ in modifying the p53 response to cytotoxic therapy, which can be modulated for therapeutic gain using these compounds.}, } @article {pmid29295931, year = {2018}, author = {Horn, ME and Nicoll, RA}, title = {Somatostatin and parvalbumin inhibitory synapses onto hippocampal pyramidal neurons are regulated by distinct mechanisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {589-594}, pmid = {29295931}, issn = {1091-6490}, support = {R01 MH070957/MH/NIMH NIH HHS/United States ; R37 MH038256/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Cell Adhesion Molecules, Neuronal/metabolism ; Excitatory Postsynaptic Potentials ; Hippocampus/*cytology/metabolism ; Inhibitory Postsynaptic Potentials ; Interneurons/metabolism ; Membrane Proteins/metabolism ; Mice ; Mice, Transgenic ; Nerve Tissue Proteins/metabolism ; Parvalbumins/genetics/*metabolism ; Pyramidal Cells/*metabolism ; Somatostatin/genetics/*metabolism ; Synapses/genetics/*metabolism ; }, abstract = {Excitation-inhibition balance is critical for optimal brain function, yet the mechanisms underlying the tuning of inhibition from different populations of inhibitory neurons are unclear. Here, we found evidence for two distinct pathways through which excitatory neurons cell-autonomously modulate inhibitory synapses. Synapses from parvalbumin-expressing interneurons onto hippocampal pyramidal neurons are regulated by neuronal firing, signaling through L-type calcium channels. Synapses from somatostatin-expressing interneurons are regulated by NMDA receptors, signaling through R-type calcium channels. Thus, excitatory neurons can cell-autonomously regulate their inhibition onto different subcellular compartments through their input (glutamatergic signaling) and their output (firing). Separately, while somatostatin and parvalbumin synapses onto excitatory neurons are both dependent on a common set of postsynaptic proteins, including gephyrin, collybistin, and neuroligin-2, decreasing neuroligin-3 expression selectively decreases inhibition from somatostatin interneurons, and overexpression of neuroligin-3 selectively enhances somatostatin inhibition. These results provide evidence that excitatory neurons can selectively regulate two distinct sets of inhibitory synapses.}, } @article {pmid29295930, year = {2018}, author = {Tessmer, MH and Anderson, DM and Pickrum, AM and Riegert, MO and Moretti, R and Meiler, J and Feix, JB and Frank, DW}, title = {Identification of a ubiquitin-binding interface using Rosetta and DEER.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {525-530}, pmid = {29295930}, issn = {1091-6490}, support = {R01 GM080403/GM/NIGMS NIH HHS/United States ; S10 OD011937/OD/NIH HHS/United States ; R01 GM073151/GM/NIGMS NIH HHS/United States ; R01 AI104922/AI/NIAID NIH HHS/United States ; S10 RR022422/RR/NCRR NIH HHS/United States ; P41 EB001980/EB/NIBIB NIH HHS/United States ; R01 GM114234/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacterial Proteins/*chemistry/genetics/metabolism ; Crystallography, X-Ray ; Electron Spin Resonance Spectroscopy/*methods ; Models, Molecular ; Protein Binding ; Protein Domains ; Pseudomonas aeruginosa/*enzymology/genetics/metabolism ; Ubiquitin/*chemistry/metabolism ; }, abstract = {ExoU is a type III-secreted cytotoxin expressing A2 phospholipase activity when injected into eukaryotic target cells by the bacterium Pseudomonas aeruginosa The enzymatic activity of ExoU is undetectable in vitro unless ubiquitin, a required cofactor, is added to the reaction. The role of ubiquitin in facilitating ExoU enzymatic activity is poorly understood but of significance for designing inhibitors to prevent tissue injury during infections with strains of P. aeruginosa producing this toxin. Most ubiquitin-binding proteins, including ExoU, demonstrate a low (micromolar) affinity for monoubiquitin (monoUb). Additionally, ExoU is a large and dynamic protein, limiting the applicability of traditional structural techniques such as NMR and X-ray crystallography to define this protein-protein interaction. Recent advancements in computational methods, however, have allowed high-resolution protein modeling using sparse data. In this study, we combine double electron-electron resonance (DEER) spectroscopy and Rosetta modeling to identify potential binding interfaces of ExoU and monoUb. The lowest-energy scoring model was tested using biochemical, biophysical, and biological techniques. To verify the binding interface, Rosetta was used to design a panel of mutations to modulate binding, including one variant with enhanced binding affinity. Our analyses show the utility of computational modeling when combined with sensitive biological assays and biophysical approaches that are exquisitely suited for large dynamic proteins.}, } @article {pmid29295929, year = {2018}, author = {Chen, C and Wang, Z and Zhang, Z and Liu, X and Kang, SS and Zhang, Y and Ye, K}, title = {The prodrug of 7,8-dihydroxyflavone development and therapeutic efficacy for treating Alzheimer's disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {578-583}, pmid = {29295929}, issn = {1091-6490}, support = {R01 DC010204/DC/NIDCD NIH HHS/United States ; RF1 AG051538/AG/NIA NIH HHS/United States ; }, mesh = {Alzheimer Disease/*drug therapy/genetics/metabolism ; Amyloid beta-Protein Precursor/genetics/metabolism ; Animals ; Brain/drug effects/metabolism ; Disease Models, Animal ; Flavones/*administration & dosage/chemical synthesis/chemistry/pharmacokinetics ; Humans ; Male ; Membrane Glycoproteins/genetics/metabolism ; Mice ; Mice, Transgenic ; Prodrugs/*administration & dosage/chemical synthesis/chemistry/pharmacokinetics ; Protein-Tyrosine Kinases/genetics/metabolism ; }, abstract = {The BDNF mimetic compound 7,8-dihydroxyflavone (7,8-DHF), a potent small molecular TrkB agonist, displays prominent therapeutic efficacy against Alzheimer's disease (AD). However, 7,8-DHF has only modest oral bioavailability and a moderate pharmacokinetic (PK) profile. To alleviate these preclinical obstacles, we used a prodrug strategy for elevating 7,8-DHF oral bioavailability and brain exposure, and found that the optimal prodrug R13 has favorable properties and dose-dependently reverses the cognitive defects in an AD mouse model. We synthesized a large number of 7,8-DHF derivatives via ester or carbamate group modification on the catechol ring in the parent compound. Using in vitro absorption, distribution, metabolism, and excretion assays, combined with in vivo PK studies, we identified a prodrug, R13, that prominently up-regulates 7,8-DHF PK profiles. Chronic oral administration of R13 activated TrkB signaling and prevented Aβ deposition in 5XFAD AD mice, inhibiting the pathological cleavage of APP and Tau by AEP. Moreover, R13 inhibited the loss of hippocampal synapses and ameliorated memory deficits in a dose-dependent manner. These results suggest that the prodrug R13 is an optimal therapeutic agent for treating AD.}, } @article {pmid29295928, year = {2018}, author = {Bergman, JP and Bovyn, MJ and Doval, FF and Sharma, A and Gudheti, MV and Gross, SP and Allard, JF and Vershinin, MD}, title = {Cargo navigation across 3D microtubule intersections.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {537-542}, pmid = {29295928}, issn = {1091-6490}, support = {R01 GM123068/GM/NIGMS NIH HHS/United States ; T32 EB009418/EB/NIBIB NIH HHS/United States ; }, mesh = {Biological Transport ; Cytoskeleton/metabolism ; Humans ; Imaging, Three-Dimensional ; Kinesin/chemistry/metabolism ; Kinetics ; Microtubules/*chemistry/*metabolism ; Models, Biological ; Models, Theoretical ; Protein Binding ; }, abstract = {The eukaryotic cell's microtubule cytoskeleton is a complex 3D filament network. Microtubules cross at a wide variety of separation distances and angles. Prior studies in vivo and in vitro suggest that cargo transport is affected by intersection geometry. However, geometric complexity is not yet widely appreciated as a regulatory factor in its own right, and mechanisms that underlie this mode of regulation are not well understood. We have used our recently reported 3D microtubule manipulation system to build filament crossings de novo in a purified in vitro environment and used them to assay kinesin-1-driven model cargo navigation. We found that 3D microtubule network geometry indeed significantly influences cargo routing, and in particular that it is possible to bias a cargo to pass or switch just by changing either filament spacing or angle. Furthermore, we captured our experimental results in a model which accounts for full 3D geometry, stochastic motion of the cargo and associated motors, as well as motor force production and force-dependent behavior. We used a combination of experimental and theoretical analysis to establish the detailed mechanisms underlying cargo navigation at microtubule crossings.}, } @article {pmid29295927, year = {2018}, author = {Qiu, M and Wang, D and Liang, W and Liu, L and Zhang, Y and Chen, X and Sang, DK and Xing, C and Li, Z and Dong, B and Xing, F and Fan, D and Bao, S and Zhang, H and Cao, Y}, title = {Novel concept of the smart NIR-light-controlled drug release of black phosphorus nanostructure for cancer therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {501-506}, pmid = {29295927}, issn = {1091-6490}, mesh = {Animals ; Antineoplastic Agents/*administration & dosage/chemistry ; Cell Line, Tumor ; Delayed-Action Preparations/*administration & dosage/chemistry ; Drug Carriers/chemistry/*radiation effects ; Drug Delivery Systems/instrumentation/*methods ; Humans ; Hydrogels/chemistry/radiation effects ; Infrared Rays ; Mice ; Mice, Nude ; Nanostructures/chemistry/*radiation effects ; Neoplasms/*drug therapy ; Phosphorus/chemistry ; }, abstract = {A biodegradable drug delivery system (DDS) is one the most promising therapeutic strategies for cancer therapy. Here, we propose a unique concept of light activation of black phosphorus (BP) at hydrogel nanostructures for cancer therapy. A photosensitizer converts light into heat that softens and melts drug-loaded hydrogel-based nanostructures. Drug release rates can be accurately controlled by light intensity, exposure duration, BP concentration, and hydrogel composition. Owing to sufficiently deep penetration of near-infrared (NIR) light through tissues, our BP-based system shows high therapeutic efficacy for treatment of s.c. cancers. Importantly, our drug delivery system is completely harmless and degradable in vivo. Together, our work proposes a unique concept for precision cancer therapy by external light excitation to release cancer drugs. If these findings are successfully translated into the clinic, millions of patients with cancer will benefit from our work.}, } @article {pmid29295926, year = {2018}, author = {Ren, W and Hu, L and Guo, L and Zhang, J and Tang, L and Zhang, E and Zhang, J and Luo, S and Tang, J and Chen, X}, title = {Preservation of the genetic diversity of a local common carp in the agricultural heritage rice-fish system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E546-E554}, pmid = {29295926}, issn = {1091-6490}, mesh = {Agriculture/*methods ; Animals ; Carps/*genetics ; China ; *Genetic Variation ; Microsatellite Repeats ; Oryza/physiology ; Phylogeny ; }, abstract = {We examined how traditional farmers preserve the genetic diversity of a local common carp (Cyprinus carpio), which is locally referred to as "paddy field carp" (PF-carp), in a "globally important agricultural heritage system" (GIAHS), i.e., the 1,200-y-old rice-fish coculture system in Zhejiang Province, China. Our molecular and morphological analysis showed that the PF-carp has changed into a distinct local population with higher genetic diversity and diverse color types. Within this GIAHS region, PF-carps exist as a continuous metapopulation, although three genetic groups could be identified by microsatellite markers. Thousands of small farmer households interdependently obtained fry and parental carps for their own rice-fish production, resulting in a high gene flow and large numbers of parent carps distributing in a mosaic pattern in the region. Landscape genetic analysis indicated that farmers' connectivity was one of the major factors that shaped this genetic pattern. Population viability analysis further revealed that the numbers of these interconnected small farmer households and their connection intensity affect the carps' inherent genetic diversity. The practice of mixed culturing of carps with diverse color types helped to preserve a wide range of genetic resources in the paddy field. This widespread traditional practice increases fish yield and resource use, which, in return, encourages famers to continue their practice of selecting and conserving diverse color types of PF-carp. Our results suggested that traditional farmers secure the genetic diversity of PF-carp and its viability over generations in this region through interdependently incubating and mixed-culturing practices within the rice-fish system.}, } @article {pmid29295925, year = {2018}, author = {Sahli, R and Pallares, G and Ducottet, C and Ben Ali, IE and Al Akhrass, S and Guibert, M and Scheibert, J}, title = {Evolution of real contact area under shear and the value of static friction of soft materials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {471-476}, pmid = {29295925}, issn = {1091-6490}, abstract = {The frictional properties of a rough contact interface are controlled by its area of real contact, the dynamical variations of which underlie our modern understanding of the ubiquitous rate-and-state friction law. In particular, the real contact area is proportional to the normal load, slowly increases at rest through aging, and drops at slip inception. Here, through direct measurements on various contacts involving elastomers or human fingertips, we show that the real contact area also decreases under shear, with reductions as large as 30[Formula: see text], starting well before macroscopic sliding. All data are captured by a single reduction law enabling excellent predictions of the static friction force. In elastomers, the area-reduction rate of individual contacts obeys a scaling law valid from micrometer-sized junctions in rough contacts to millimeter-sized smooth sphere/plane contacts. For the class of soft materials used here, our results should motivate first-order improvements of current contact mechanics models and prompt reinterpretation of the rate-and-state parameters.}, } @article {pmid29295924, year = {2018}, author = {Pedraja, F and Hofmann, V and Lucas, KM and Young, C and Engelmann, J and Lewis, JE}, title = {Motion parallax in electric sensing.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {573-577}, pmid = {29295924}, issn = {1091-6490}, abstract = {A crucial step in forming spatial representations of the environment involves the estimation of relative distance. Active sampling through specific movements is considered essential for optimizing the sensory flow that enables the extraction of distance cues. However, in electric sensing, direct evidence for the generation and exploitation of sensory flow is lacking. Weakly electric fish rely on a self-generated electric field to navigate and capture prey in the dark. This electric sense provides a blurred representation of the environment, making the exquisite sensory abilities of electric fish enigmatic. Stereotyped back-and-forth swimming patterns reminiscent of visual peering movements are suggestive of the active generation of sensory flow, but how motion contributes to the disambiguation of the electrosensory world remains unclear. Here, we show that a dipole-like electric field geometry coupled to motion provides the physical basis for a nonvisual parallax. We then show in a behavioral assay that this cue is used for electrosensory distance perception across phylogenetically distant taxa of weakly electric fish. Notably, these species electrically sample the environment in temporally distinct ways (using discrete pulses or quasisinusoidal waves), suggesting a ubiquitous role for parallax in electric sensing. Our results demonstrate that electrosensory information is extracted from sensory flow and used in a behaviorally relevant context. A better understanding of motion-based electric sensing will provide insight into the sensorimotor coordination required for active sensing in general and may lead to improved electric field-based imaging applications in a variety of contexts.}, } @article {pmid29295923, year = {2018}, author = {Ye, X and Mayne, L and Kan, ZY and Englander, SW}, title = {Folding of maltose binding protein outside of and in GroEL.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {519-524}, pmid = {29295923}, issn = {1091-6490}, support = {R01 GM031847/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/metabolism ; Chaperonin 60/chemistry/genetics/*metabolism ; Escherichia coli/*chemistry/genetics/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Kinetics ; Maltose-Binding Proteins/*chemistry/genetics/metabolism ; Protein Binding ; Protein Conformation ; *Protein Folding ; }, abstract = {We used hydrogen exchange-mass spectrometry (HX MS) and fluorescence to compare the folding of maltose binding protein (MBP) in free solution and in the GroEL/ES cavity. Upon refolding, MBP initially collapses into a dynamic molten globule-like ensemble, then forms an obligatory on-pathway native-like folding intermediate (1.2 seconds) that brings together sequentially remote segments and then folds globally after a long delay (30 seconds). A single valine to glycine mutation imposes a definable folding defect, slows early intermediate formation by 20-fold, and therefore subsequent global folding by approximately twofold. Simple encapsulation within GroEL repairs the folding defect and reestablishes fast folding, with or without ATP-driven cycling. Further examination exposes the structural mechanism. The early folding intermediate is stabilized by an organized cluster of 24 hydrophobic side chains. The cluster preexists in the collapsed ensemble before the H-bond formation seen by HX MS. The V9G mutation slows folding by disrupting the preintermediate cluster. GroEL restores wild-type folding rates by restabilizing the preintermediate, perhaps by a nonspecific equilibrium compression effect within its tightly confining central cavity. These results reveal an active GroEL function other than previously proposed mechanisms, suggesting that GroEL possesses different functionalities that are able to relieve different folding problems. The discovery of the preintermediate, its mutational destabilization, and its restoration by GroEL encapsulation was made possible by the measurement of a previously unexpected type of low-level HX protection, apparently not dependent on H-bonding, that may be characteristic of proteins in confined spaces.}, } @article {pmid29295922, year = {2018}, author = {Ha, BH and Boggon, TJ}, title = {CDC42 binds PAK4 via an extended GTPase-effector interface.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {531-536}, pmid = {29295922}, issn = {1091-6490}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 OD012331/OD/NIH HHS/United States ; S10 OD018007/OD/NIH HHS/United States ; P41 GM111244/GM/NIGMS NIH HHS/United States ; R01 GM102262/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Binding Sites ; Crystallography, X-Ray ; Humans ; Models, Molecular ; Molecular Sequence Data ; Protein Binding ; Protein Domains ; cdc42 GTP-Binding Protein/*chemistry/genetics/*metabolism ; p21-Activated Kinases/*chemistry/genetics/*metabolism ; }, abstract = {The p21-activated kinase (PAK) group of serine/threonine kinases are downstream effectors of RHO GTPases and play important roles in regulation of the actin cytoskeleton, cell growth, survival, polarity, and development. Here we probe the interaction of the type II PAK, PAK4, with RHO GTPases. Using solution scattering we find that the full-length PAK4 heterodimer with CDC42 adopts primarily a compact organization. X-ray crystallography reveals the molecular nature of the interaction between PAK4 and CDC42 and shows that in addition to the canonical PAK4 CDC42/RAC interactive binding (CRIB) domain binding to CDC42 there are unexpected contacts involving the PAK4 kinase C-lobe, CDC42, and the PAK4 polybasic region. These additional interactions modulate kinase activity and increase the binding affinity of CDC42 for full-length PAK4 compared with the CRIB domain alone. We therefore show that the interaction of CDC42 with PAK4 can influence kinase activity in a previously unappreciated manner.}, } @article {pmid29295921, year = {2018}, author = {Ingelsson, B and Söderberg, D and Strid, T and Söderberg, A and Bergh, AC and Loitto, V and Lotfi, K and Segelmark, M and Spyrou, G and Rosén, A}, title = {Lymphocytes eject interferogenic mitochondrial DNA webs in response to CpG and non-CpG oligodeoxynucleotides of class C.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E478-E487}, pmid = {29295921}, issn = {1091-6490}, mesh = {Animals ; Cell Death ; Cells, Cultured ; CpG Islands/*physiology ; DNA, Mitochondrial/*metabolism ; DNA-Binding Proteins ; Humans ; Lymphocyte Activation ; Lymphocytes/*physiology ; Membrane Proteins ; Monocytes ; Neutrons ; Oligodeoxyribonucleotides/*classification ; Reactive Nitrogen Species ; Reactive Oxygen Species ; Receptors, Antigen, B-Cell ; Toll-Like Receptor 9 ; }, abstract = {Circulating mitochondrial DNA (mtDNA) is receiving increasing attention as a danger-associated molecular pattern in conditions such as autoimmunity, cancer, and trauma. We report here that human lymphocytes [B cells, T cells, natural killer (NK) cells], monocytes, and neutrophils derived from healthy blood donors, as well as B cells from chronic lymphocytic leukemia patients, rapidly eject mtDNA as web filament structures upon recognition of CpG and non-CpG oligodeoxynucleotides of class C. The release was quenched by ZnCl2, independent of cell death (apoptosis, necrosis, necroptosis, autophagy), and continued in the presence of TLR9 signaling inhibitors. B-cell mtDNA webs were distinct from neutrophil extracellular traps concerning structure, reactive oxygen species (ROS) dependence, and were devoid of antibacterial proteins. mtDNA webs acted as rapid (within minutes) messengers, priming antiviral type I IFN production. In summary, our findings point at a previously unrecognized role for lymphocytes in antimicrobial defense, utilizing mtDNA webs as signals in synergy with cytokines and natural antibodies, and cast light on the interplay between mitochondria and the immune system.}, } @article {pmid29295920, year = {2018}, author = {Han, KH and Arlian, BM and Macauley, MS and Paulson, JC and Lerner, RA}, title = {Migration-based selections of antibodies that convert bone marrow into trafficking microglia-like cells that reduce brain amyloid β.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E372-E381}, pmid = {29295920}, issn = {1091-6490}, mesh = {Alzheimer Disease ; Amyloid beta-Peptides/*physiology ; Animals ; Antibodies/*physiology ; Bone Marrow Cells/*physiology ; Brain/pathology/*physiology ; Cell Differentiation ; Cell Line ; Cell Movement ; Disease Models, Animal ; Humans ; Luminescent Measurements ; Mice ; Mice, Inbred Strains ; Mice, Transgenic ; Microglia/*cytology/physiology ; }, abstract = {One goal of regenerative medicine is to repair damaged tissue. This requires not only generating new cells of the proper phenotype, but also selecting for those that properly integrate into sites of injury. In our laboratory we are using a cell-migration-based in vivo selection system to generate antibodies that induce cells to both differentiate and selectively localize to different tissues. Here we describe an antibody that induces bone marrow stem cells to differentiate into microglia-like cells that traffic to the brain where they organize into typical networks. Interestingly, in the APP/PS1 Alzheimer's disease mouse model, these induced microglia-like cells are found at sites of plaque formation and significantly reduce their number. These results raise the intriguing question as to whether one can use such antibody-induced differentiation of stem cells to essentially recapitulate embryogenesis in adults to discover cells that can regenerate damaged organ systems.}, } @article {pmid29295919, year = {2018}, author = {Bauters, M and Drake, TW and Verbeeck, H and Bodé, S and Hervé-Fernández, P and Zito, P and Podgorski, DC and Boyemba, F and Makelele, I and Cizungu Ntaboba, L and Spencer, RGM and Boeckx, P}, title = {High fire-derived nitrogen deposition on central African forests.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {549-554}, pmid = {29295919}, issn = {1091-6490}, mesh = {Air/*analysis ; Congo ; Forests ; Mass Spectrometry ; Nitrogen/*analysis/metabolism ; Trees/growth & development/*metabolism ; }, abstract = {Atmospheric nitrogen (N) deposition is an important determinant of N availability for natural ecosystems worldwide. Increased anthropogenic N deposition shifts the stoichiometric equilibrium of ecosystems, with direct and indirect impacts on ecosystem functioning and biogeochemical cycles. Current simulation data suggest that remote tropical forests still receive low atmospheric N deposition due to a lack of proximate industry, low rates of fossil fuel combustion, and absence of intensive agriculture. We present field-based N deposition data for forests of the central Congo Basin, and use ultrahigh-resolution mass spectrometry to characterize the organic N fraction. Additionally, we use satellite data and modeling for atmospheric N source apportionment. Our results indicate that these forests receive 18.2 kg N hectare-1 years-1 as wet deposition, with dry deposition via canopy interception adding considerably to this flux. We also show that roughly half of the N deposition is organic, which is often ignored in N deposition measurements and simulations. The source of atmospheric N is predominantly derived from intensive seasonal burning of biomass on the continent. This high N deposition has important implications for the ecology of the Congo Basin and for global biogeochemical cycles more broadly.}, } @article {pmid29295918, year = {2018}, author = {Stevens, CF}, title = {Conserved features of the primate face code.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {584-588}, pmid = {29295918}, issn = {1091-6490}, mesh = {Animals ; *Face ; Humans ; Models, Neurological ; Neurons/chemistry/*physiology ; *Pattern Recognition, Visual ; Visual Cortex/physiology ; }, abstract = {A recent paper demonstrated that the pattern of firing rates across ∼100 neurons in the anterior medial face patch is closely related to which human face (of 2,000) had been presented to a monkey [Chang L, Tsao DY (2017) Cell 169:1013-1028]. In addition, the firing rates for these neurons can be predicted for a novel human face. Although it is clear from this work that the firing rates of these face patch neurons encode faces, the properties of the face code have not yet been fully described. Based on an analysis of 98 neurons responding to 2,000 faces, I conclude that the anterior medial face patch uses a combinatorial rate code, one with an exponential distribution of neuron rates that has a mean rate conserved across faces. Thus, the face code is maximally informative (technically, maximum entropy) and is very similar to the code used by the fruit fly olfactory system.}, } @article {pmid29295917, year = {2018}, author = {Miskin, MZ and Dorsey, KJ and Bircan, B and Han, Y and Muller, DA and McEuen, PL and Cohen, I}, title = {Graphene-based bimorphs for micron-sized, autonomous origami machines.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {466-470}, pmid = {29295917}, issn = {1091-6490}, abstract = {Origami-inspired fabrication presents an attractive platform for miniaturizing machines: thinner layers of folding material lead to smaller devices, provided that key functional aspects, such as conductivity, stiffness, and flexibility, are persevered. Here, we show origami fabrication at its ultimate limit by using 2D atomic membranes as a folding material. As a prototype, we bond graphene sheets to nanometer-thick layers of glass to make ultrathin bimorph actuators that bend to micrometer radii of curvature in response to small strain differentials. These strains are two orders of magnitude lower than the fracture threshold for the device, thus maintaining conductivity across the structure. By patterning 2-[Formula: see text]m-thick rigid panels on top of bimorphs, we localize bending to the unpatterned regions to produce folds. Although the graphene bimorphs are only nanometers thick, they can lift these panels, the weight equivalent of a 500-nm-thick silicon chip. Using panels and bimorphs, we can scale down existing origami patterns to produce a wide range of machines. These machines change shape in fractions of a second when crossing a tunable pH threshold, showing that they sense their environments, respond, and perform useful functions on time and length scales comparable with microscale biological organisms. With the incorporation of electronic, photonic, and chemical payloads, these basic elements will become a powerful platform for robotics at the micrometer scale.}, } @article {pmid29295889, year = {2018}, author = {Svitkina, T}, title = {The Actin Cytoskeleton and Actin-Based Motility.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, doi = {10.1101/cshperspect.a018267}, pmid = {29295889}, issn = {1943-0264}, support = {R01 GM095977/GM/NIGMS NIH HHS/United States ; }, abstract = {The actin cytoskeleton-a collection of actin filaments with their accessory and regulatory proteins-is the primary force-generating machinery in the cell. It can produce pushing (protrusive) forces through coordinated polymerization of multiple actin filaments or pulling (contractile) forces through sliding actin filaments along bipolar filaments of myosin II. Both force types are particularly important for whole-cell migration, but they also define and change the cell shape and mechanical properties of the cell surface, drive the intracellular motility and morphogenesis of membrane organelles, and allow cells to form adhesions with each other and with the extracellular matrix.}, } @article {pmid29295774, year = {2018}, author = {Erslev, T}, title = {A brain worth keeping? Waste, value and time in contemporary brain banking.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {67}, number = {}, pages = {16-23}, doi = {10.1016/j.shpsc.2017.12.002}, pmid = {29295774}, issn = {1879-2499}, mesh = {*Brain ; Humans ; Tissue Banks/*economics/statistics & numerical data ; }, abstract = {If a temporal rather than spatial concept of waste is adopted, novel categories emerge which are useful for identifying and understanding logics of temporality at play in determining what is kept in contemporary brain banks, and reveal that brain banks are constituted by more than stored materials. First, I apply the categories analytically on a recent UK brain banking discussion among professionals. This analysis highlights the importance of data in brain banks, as well as the centrality of ideas about pasts and futures in the discussions. Secondly, I investigate the case of a seven decades old, Danish brain bank which had been reduced to its physically stored material for 24 years, before being reinstituted in 2006. This case demonstrates the importance of material and conceptual infrastructures that co-constitute a collection, as they make up an experimental system that is crucial to maintaining the collection's continued relevance and usefulness as a scientific institution.}, } @article {pmid29295714, year = {2018}, author = {Meng, F and Wang, C and Kurgan, L}, title = {fDETECT webserver: fast predictor of propensity for protein production, purification, and crystallization.}, journal = {BMC bioinformatics}, volume = {18}, number = {1}, pages = {580}, doi = {10.1186/s12859-017-1995-z}, pmid = {29295714}, issn = {1471-2105}, mesh = {Amino Acid Sequence ; Crystallization ; Crystallography, X-Ray ; Databases, Protein ; Humans ; *Internet ; Proteins/*chemistry/*isolation & purification ; ROC Curve ; Time Factors ; }, abstract = {BACKGROUND: Development of predictors of propensity of protein sequences for successful crystallization has been actively pursued for over a decade. A few novel methods that expanded the scope of these predictions to address additional steps of protein production and structure determination pipelines were released in recent years. The predictive performance of the current methods is modest. This is because the only input that they use is the protein sequence and since the experimental annotations of these data might be inconsistent given that they were collected across many laboratories and centers. However, even these modest levels of predictive quality are still practical compared to the reported low success rates of crystallization, which are below 10%. We focus on another important aspect related to a high computational cost of running the predictors that offer the expanded scope.

RESULTS: We introduce a novel fDETECT webserver that provides very fast and modestly accurate predictions of the success of protein production, purification, crystallization, and structure determination. Empirical tests on two datasets demonstrate that fDETECT is more accurate than the only other similarly fast method, and similarly accurate and three orders of magnitude faster than the currently most accurate predictors. Our method predicts a single protein in about 120 milliseconds and needs less than an hour to generate the four predictions for an entire human proteome. Moreover, we empirically show that fDETECT secures similar levels of predictive performance when compared with four representative methods that only predict success of crystallization, while it also provides the other three predictions. A webserver that implements fDETECT is available at http://biomine.cs.vcu.edu/servers/fDETECT/ .

CONCLUSIONS: fDETECT is a computational tool that supports target selection for protein production and X-ray crystallography-based structure determination. It offers predictive quality that matches or exceeds other state-of-the-art tools and is especially suitable for the analysis of large protein sets.}, } @article {pmid29295711, year = {2018}, author = {Zhao, C and Zhao, G and Geng, Z and Wang, Z and Wang, K and Liu, S and Zhang, H and Guo, B and Geng, J}, title = {Physical mapping and candidate gene prediction of fertility restorer gene of cytoplasmic male sterility in cotton.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {6}, pmid = {29295711}, issn = {1471-2164}, support = {2016ZX08005-005-009//Genetically Modified Organisms Breeding Major Projects of The Ministry of Science and Technology of China/International ; 16226321D//Science and Technology Plan Projects of Hebei Province of China/International ; }, mesh = {Fertility ; *Genes, Plant ; Gossypium/*genetics ; High-Throughput Nucleotide Sequencing ; INDEL Mutation ; Physical Chromosome Mapping ; *Plant Infertility ; *Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Cytoplasmic male sterility (CMS) is a maternally inherited trait failing to produce functional pollen. It plays a pivotal role in the exploitation of crop heterosis. The specific locus amplified fragment sequencing (SLAF-seq) as a high-resolution strategy for the identification of new SNPs on a large-scale is gradually applied for functional gene mining. The current study combined the bulked segregant analysis (BSA) with SLAF-seq to identify the candidate genes associated with fertility restorer gene (Rf) in CMS cotton.

METHODS: Illumina sequencing systematically investigated the parents. A segregating population comprising of 30 + 30 F2 individuals was developed using 3096A (female parent) as sterile and 866R (male parent) as a restorer. The original data obtained by dual-index sequencing were analyzed to obtain the reads of each sample that were compared to the reference genome in order to identify the SLAF tag with a polymorphism in parent lines and the SNP with read-associated coverage. Based on SLAF tags, SNP-index analysis, Euclidean distance (ED) correlation analysis, and whole genome resequencing, the hot regions were annotated.

RESULTS: A total of 165,007 high-quality SLAF tags, with an average depth of 47.90× in the parents and 50.78× in F2 individuals, were sequenced. In addition, a total of 137,741 SNPs were detected: 113,311 and 98,861 SNPs in the male and female parent, respectively. A correlation analysis by SNP-index and ED initially located the candidate gene on 1.35 Mb of chrD05, and 20 candidate genes were identified. These genes were involved in genetic variations, single base mutations, insertions, and deletions. Moreover, 42 InDel markers of the whole genome resequencing were also detected.

CONCLUSIONS: In this study, associated markers identified by super-BSA could accelerate the study of CMS in cotton, and as well as in other crops. Some of the 20 genes' preliminary characteristics provided useful information for further studies on CMS crops.}, } @article {pmid29295707, year = {2018}, author = {Lee, BY and Kim, DH and Kim, HS and Kim, BM and Han, J and Lee, JS}, title = {Identification of 74 cytochrome P450 genes and co-localized cytochrome P450 genes of the CYP2K, CYP5A, and CYP46A subfamilies in the mangrove killifish Kryptolebias marmoratus.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {7}, pmid = {29295707}, issn = {1471-2164}, support = {20140428//Collaborative Genome Program/International ; 2017R1D1A1B03036026//National Research Foundation of Korea/International ; }, mesh = {Animals ; Cytochrome P-450 Enzyme System/classification/*genetics ; Cytochrome P450 Family 46/genetics ; Fish Proteins/classification/*genetics ; Genes, Duplicate ; Killifishes/*genetics ; *Multigene Family ; Phylogeny ; Synteny ; }, abstract = {BACKGROUND: The mangrove killifish Kryptolebias marmoratus is the only vertebrate that reproduces by self-fertilizing and is an important model species in genetics and marine ecotoxicology. Using whole-genome and transcriptome sequences, we identified all members of the cytochrome P450 (CYP) family in this model teleost and compared them with those of other teleosts.

RESULTS: A total of 74 cytochrome P450 genes and one pseudogene were identified in K. marmoratus. Phylogenetic analysis indicated that the CYP genes in clan 2 were most expanded, while synteny analysis with other species showed orthologous relationships of CYP subfamilies among teleosts. In addition to the CYP2K expansions, five tandem duplicated gene copies of CYP5A were observed. These features were unique to K. marmoratus.

CONCLUSIONS: These results shed a light on CYP gene evolution, particularly the co-localized CYP2K, CYP5A, and CYP46A subfamilies in fish. Future studies of CYP expression could identify specific endogenous and exogenous environmental factors that triggered the evolution of tandem CYP duplication in K. marmoratus.}, } @article {pmid29295704, year = {2018}, author = {Nie, Z and Wang, Y and Wu, C and Li, Y and Kang, G and Qin, H and Zeng, R}, title = {Acyl-CoA-binding protein family members in laticifers are possibly involved in lipid and latex metabolism of Hevea brasiliensis (the Para rubber tree).}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {5}, pmid = {29295704}, issn = {1471-2164}, support = {ZDKJ2016020//Major Scientific & Technological Projects of Hainan Province/International ; 31770642//National Natural Science Foundation of China/International ; 1630022015001//Central Public-interest Scientific Institution Basal Research Fund for Chinese Academy of Tropical Agricultural Sciences/International ; }, mesh = {Carrier Proteins/chemistry/classification/genetics/*metabolism ; Gene Expression ; Hevea/genetics/*metabolism ; Latex/*metabolism ; Lipid Metabolism ; Multigene Family ; Phylogeny ; Plant Proteins/chemistry/classification/genetics/*metabolism ; Protein Domains ; }, abstract = {BACKGROUND: Acyl-CoA-binding proteins (ACBPs) are mainly involved in acyl-CoA ester binding and trafficking in eukaryotic cells, and their various functions have been characterized in model plants, such as Arabidopsis thaliana (A. thaliana), Oryza sativa (rice), and other plant species. In the present study, genome-wide mining and expression analysis of ACBP genes was performed on Hevea brasiliensis (the para rubber tree), the most important latex-producing crop in the world.

RESULTS: Six members of the H. brasiliensis ACBP family genes, designated HbACBP1-HbACBP6, were identified from the H. brasiliensis genome. They can be categorized into four classes with different amino acid sequences and domain structures based on the categorization of their A. thaliana counterparts. Phylogenetic analysis shows that the HbACBPs were clustered with those of other closely related species, such as Manihot esculenta, Ricinus communis, and Jatropha carcas, but were further from those of A. thaliana, a distantly related species. Expression analysis demonstrated that the HbACBP1 and HbACBP2 genes are more prominently expressed in H. brasiliensis latex, and their expression can be significantly enhanced by bark tapping (a mechanical wound) and jasmonic acid stimulation, whereas HbACBP3-HbACBP6 had almost the same expression patterns with relatively high levels in mature leaves and male flowers, but a markedly low abundance in the latex. HbACBP1 and HbACBP2 may have crucial roles in lipid and latex metabolism in laticifers, so their subcellular location was further investigated and the results indicated that HbACBP1 is a cytosol protein, whereas HbACBP2 is an endoplasmic reticulum-associated ACBP.

CONCLUSIONS: In this study, the H. brasiliensis ACBP family genes were identified. Phylogenetic analyses of the HbABCPs indicate that there is a high conservation and evolutionary relationship between ACBPs in land plants. The HbACBPs are organ/tissue-specifically expressed and have different expression patterns in response to stimulation by bark tapping or ethrel/jasmonic acid. HbACBP1 and HbACBP2 are two important latex ACBPs that might be involved in the lipid and latex metabolism. The results may provide valuable information for further investigations into the biological functions of HbACBPs during latex metabolism and stress responses in H. brasiliensis.}, } @article {pmid29295702, year = {2018}, author = {Islam, MT and Sarkar, SK and Sultana, N and Begum, MN and Bhuyan, GS and Talukder, S and Muraduzzaman, AKM and Alauddin, M and Islam, MS and Biswas, PP and Biswas, A and Qadri, SK and Shirin, T and Banu, B and Sadya, S and Hussain, M and Sarwardi, G and Khan, WA and Mannan, MA and Shekhar, HU and Chowdhury, EK and Sajib, AA and Akhteruzzaman, S and Qadri, SS and Qadri, F and Mannoor, K}, title = {High resolution melting curve analysis targeting the HBB gene mutational hot-spot offers a reliable screening approach for all common as well as most of the rare beta-globin gene mutations in Bangladesh.}, journal = {BMC genetics}, volume = {19}, number = {1}, pages = {1}, pmid = {29295702}, issn = {1471-2156}, mesh = {Adolescent ; Bangladesh ; Child ; Child, Preschool ; Genetic Carrier Screening/economics/*methods ; Hemoglobin E/genetics ; Humans ; Infant ; Mutation ; Nucleic Acid Hybridization/*methods ; beta-Globins/*genetics ; beta-Thalassemia/*diagnosis/genetics ; }, abstract = {BACKGROUND: Bangladesh lies in the global thalassemia belt, which has a defined mutational hot-spot in the beta-globin gene. The high carrier frequencies of beta-thalassemia trait and hemoglobin E-trait in Bangladesh necessitate a reliable DNA-based carrier screening approach that could supplement the use of hematological and electrophoretic indices to overcome the barriers of carrier screening. With this view in mind, the study aimed to establish a high resolution melting (HRM) curve-based rapid and reliable mutation screening method targeting the mutational hot-spot of South Asian and Southeast Asian countries that encompasses exon-1 (c.1 - c.92), intron-1 (c.92 + 1 - c.92 + 130) and a portion of exon-2 (c.93 - c.217) of the HBB gene which harbors more than 95% of mutant alleles responsible for beta-thalassemia in Bangladesh.

RESULTS: Our HRM approach could successfully differentiate ten beta-globin gene mutations, namely c.79G > A, c.92 + 5G > C, c.126_129delCTTT, c.27_28insG, c.46delT, c.47G > A, c.92G > C, c.92 + 130G > C, c.126delC and c.135delC in heterozygous states from the wild type alleles, implying the significance of the approach for carrier screening as the first three of these mutations account for ~85% of total mutant alleles in Bangladesh. Moreover, different combinations of compound heterozygous mutations were found to generate melt curves that were distinct from the wild type alleles and from one another. Based on the findings, sixteen reference samples were run in parallel to 41 unknown specimens to perform direct genotyping of the beta-thalassemia specimens using HRM. The HRM-based genotyping of the unknown specimens showed 100% consistency with the sequencing result.

CONCLUSIONS: Targeting the mutational hot-spot, the HRM approach could be successfully applied for screening of beta-thalassemia carriers in Bangladesh as well as in other countries of South Asia and Southeast Asia. The approach could be a useful supplement of hematological and electrophortic indices in order to avoid false positive and false negative results.}, } @article {pmid29294405, year = {2018}, author = {Gray, HWI and Nishida, S and Welch, AJ and Moura, AE and Tanabe, S and Kiani, MS and Culloch, R and Möller, L and Natoli, A and Ponnampalam, LS and Minton, G and Gore, M and Collins, T and Willson, A and Baldwin, R and Hoelzel, AR}, title = {Cryptic lineage differentiation among Indo-Pacific bottlenose dolphins (Tursiops aduncus) in the northwest Indian Ocean.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {1-14}, doi = {10.1016/j.ympev.2017.12.027}, pmid = {29294405}, issn = {1095-9513}, mesh = {Animals ; Bottle-Nosed Dolphin/*classification/genetics ; DNA, Mitochondrial/chemistry/classification/genetics ; Genetic Loci ; Genetic Variation ; Indian Ocean ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; }, abstract = {Phylogeography can provide insight into the potential for speciation and identify geographic regions and evolutionary processes associated with species richness and evolutionary endemism. In the marine environment, highly mobile species sometimes show structured patterns of diversity, but the processes isolating populations and promoting differentiation are often unclear. The Delphinidae (oceanic dolphins) are a striking case in point and, in particular, bottlenose dolphins (Tursiops spp.). Understanding the radiation of species in this genus is likely to provide broader inference about the processes that determine patterns of biogeography and speciation, because both fine-scale structure over a range of kilometers and relative panmixia over an oceanic range are known for Tursiops populations. In our study, novel Tursiops spp. sequences from the northwest Indian Ocean (including mitogenomes and two nuDNA loci) are included in a worldwide Tursiops spp. phylogeographic analysis. We discover a new 'aduncus' type lineage in the Arabian Sea (off India, Pakistan and Oman) that diverged from the Australasian lineage ∼261 Ka. Effective management of coastal dolphins in the region will need to consider this new lineage as an evolutionarily significant unit. We propose that the establishment of this lineage could have been in response to climate change during the Pleistocene and show data supporting hypotheses for multiple divergence events, including vicariance across the Indo-Pacific barrier and in the northwest Indian Ocean. These data provide valuable transferable inference on the potential mechanisms for population and species differentiation across this geographic range.}, } @article {pmid29294404, year = {2018}, author = {Qu, M and Tang, W and Liu, Q and Wang, D and Ding, S}, title = {Genetic diversity within grouper species and a method for interspecific hybrid identification using DNA barcoding and RYR3 marker.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {46-51}, doi = {10.1016/j.ympev.2017.12.031}, pmid = {29294404}, issn = {1095-9513}, mesh = {Animals ; Biomarkers/*metabolism ; Cell Nucleus/genetics ; China ; DNA Barcoding, Taxonomic/*methods ; Electron Transport Complex IV/genetics ; Fishes/*genetics ; *Genetic Variation ; Geography ; *Hybridization, Genetic ; Mitochondria/genetics ; Oceans and Seas ; Phylogeny ; Ryanodine Receptor Calcium Release Channel/*genetics ; Species Specificity ; }, abstract = {Groupers (family Epinephelidae) are an assemblage of coral reef fishes comprising more than 160 species in 16 genera, many of which are both environmentally and economically valuable. Because of their similar morphology, variable color patterns, and tendency for interspecies hybridization, morphological identification of groupers usually leads to taxonomic confusion. To find an effective method for identifying different grouper species and hybrids, evaluate genetic diversity and uncover any synonymous or cryptic species, we sampled a total of 221 specimens representing 57 species in 9 genera in the China Seas. Both mitochondrial (mt) cytochrome oxidase subunit I (COI) and NADH dehydrogenase subunit 2 (ND2) were found to be effective barcoding genes. We also developed an efficient protocol for identifying hybrid groupers using mt markers and the nuclear RYR3 gene and found the first record of wide interspecies hybridization in genus Epinephelus. This barcoding study revealed high genetic divergence in many widespread species and possible synonyms. In addition to providing a molecular method for identifying grouper species, this study offers important resources for the further study of grouper conservation genetics, speciation, hybridization and other evolutionary traits.}, } @article {pmid29294306, year = {2018}, author = {Tasnim, S and Kelleher, ES}, title = {p53 is required for female germline stem cell maintenance in P-element hybrid dysgenesis.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {215-220}, doi = {10.1016/j.ydbio.2017.12.021}, pmid = {29294306}, issn = {1095-564X}, mesh = {Animals ; *Cell Cycle Checkpoints ; *Cellular Senescence ; *DNA Damage ; *DNA Transposable Elements ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Female ; Germ Cells/*metabolism ; *Mutation ; Tumor Suppressor Protein p53/genetics/*metabolism ; }, abstract = {Hybrid dysgenesis is a sterility syndrome resulting from the mobilization of certain transposable elements in the Drosophila germline. Particularly extreme is the hybrid dysgenesis syndrome caused by P-element DNA transposons, in which dysgenic female ovaries often contain few or no germline cells. Those offspring that are produced from dysgenic germlines exhibit high rates of de novo mutation and recombination, implicating transposition-associated DNA damage as the cause of germline loss. However, how this loss occurs, in terms of the particular cellular response that is triggered (cell cycle arrest, senescence, or cell death) remains poorly understood. We demonstrate that two components of the DNA damage response, Checkpoint kinase 2 and its downstream target p53, determine the frequency of ovarian atrophy that is associated with P-element hybrid dysgenesis. We further show that p53 is strongly induced in the germline stem cells (GSCs) of dysgenic females, and is required for their maintenance. Our observations support the critical role for p53 in conferring tolerance of transposable element activity in stem cells.}, } @article {pmid29294063, year = {2018}, author = {Featherston, J and Arakaki, Y and Hanschen, ER and Ferris, PJ and Michod, RE and Olson, BJSC and Nozaki, H and Durand, PM}, title = {The 4-Celled Tetrabaena socialis Nuclear Genome Reveals the Essential Components for Genetic Control of Cell Number at the Origin of Multicellularity in the Volvocine Lineage.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {855-870}, doi = {10.1093/molbev/msx332}, pmid = {29294063}, issn = {1537-1719}, abstract = {Multicellularity is the premier example of a major evolutionary transition in individuality and was a foundational event in the evolution of macroscopic biodiversity. The volvocine chlorophyte lineage is well suited for studying this process. Extant members span unicellular, simple colonial, and obligate multicellular taxa with germ-soma differentiation. Here, we report the nuclear genome sequence of one of the most morphologically simple organisms in this lineage-the 4-celled colonial Tetrabaena socialis and compare this to the three other complete volvocine nuclear genomes. Using conservative estimates of gene family expansions a minimal set of expanded gene families was identified that associate with the origin of multicellularity. These families are rich in genes related to developmental processes. A subset of these families is lineage specific, which suggests that at a genomic level the evolution of multicellularity also includes lineage-specific molecular developments. Multiple points of evidence associate modifications to the ubiquitin proteasomal pathway (UPP) with the beginning of coloniality. Genes undergoing positive or accelerating selection in the multicellular volvocines were found to be enriched in components of the UPP and gene families gained at the origin of multicellularity include components of the UPP. A defining feature of colonial/multicellular life cycles is the genetic control of cell number. The genomic data presented here, which includes diversification of cell cycle genes and modifications to the UPP, align the genetic components with the evolution of this trait.}, } @article {pmid29294021, year = {2018}, author = {Shin, S and Clarke, DJ and Lemmon, AR and Moriarty Lemmon, E and Aitken, AL and Haddad, S and Farrell, BD and Marvaldi, AE and Oberprieler, RG and McKenna, DD}, title = {Phylogenomic Data Yield New and Robust Insights into the Phylogeny and Evolution of Weevils.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {823-836}, doi = {10.1093/molbev/msx324}, pmid = {29294021}, issn = {1537-1719}, abstract = {The phylogeny and evolution of weevils (the beetle superfamily Curculionoidea) has been extensively studied, but many relationships, especially in the large family Curculionidae (true weevils; > 50,000 species), remain uncertain. We used phylogenomic methods to obtain DNA sequences from 522 protein-coding genes for representatives of all families of weevils and all subfamilies of Curculionidae. Most of our phylogenomic results had strong statistical support, and the inferred relationships were generally congruent with those reported in previous studies, but with some interesting exceptions. Notably, the backbone relationships of the weevil phylogeny were consistently strongly supported, and the former Nemonychidae (pine flower snout beetles) were polyphyletic, with the subfamily Cimberidinae (here elevated to Cimberididae) placed as sister group of all other weevils. The clade comprising the sister families Brentidae (straight-snouted weevils) and Curculionidae was maximally supported and the composition of both families was firmly established. The contributions of substitution modeling, codon usage and/or mutational bias to differences between trees reconstructed from amino acid and nucleotide sequences were explored. A reconstructed timetree for weevils is consistent with a Mesozoic radiation of gymnosperm-associated taxa to form most extant families and diversification of Curculionidae alongside flowering plants-first monocots, then other groups-beginning in the Cretaceous.}, } @article {pmid29294013, year = {2018}, author = {Hung, LY and Chen, YJ and Mai, TL and Chen, CY and Yang, MY and Chiang, TW and Wang, YD and Chuang, TJ}, title = {An Evolutionary Landscape of A-to-I RNA Editome across Metazoan Species.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {521-537}, pmid = {29294013}, issn = {1759-6653}, mesh = {Adenosine/*genetics ; Animals ; Cluster Analysis ; Evolution, Molecular ; Humans ; Inosine/*genetics ; RNA/*genetics ; *RNA Editing ; Sequence Analysis, RNA ; }, abstract = {Adenosine-to-inosine (A-to-I) editing is widespread across the kingdom Metazoa. However, for the lack of comprehensive analysis in nonmodel animals, the evolutionary history of A-to-I editing remains largely unexplored. Here, we detect high-confidence editing sites using clustering and conservation strategies based on RNA sequencing data alone, without using single-nucleotide polymorphism information or genome sequencing data from the same sample. We thereby unveil the first evolutionary landscape of A-to-I editing maps across 20 metazoan species (from worm to human), providing unprecedented evidence on how the editing mechanism gradually expands its territory and increases its influence along the history of evolution. Our result revealed that highly clustered and conserved editing sites tended to have a higher editing level and a higher magnitude of the ADAR motif. The ratio of the frequencies of nonsynonymous editing to that of synonymous editing remarkably increased with increasing the conservation level of A-to-I editing. These results thus suggest potentially functional benefit of highly clustered and conserved editing sites. In addition, spatiotemporal dynamics analyses reveal a conserved enrichment of editing and ADAR expression in the central nervous system throughout more than 300 Myr of divergent evolution in complex animals and the comparability of editing patterns between invertebrates and between vertebrates during development. This study provides evolutionary and dynamic aspects of A-to-I editome across metazoan species, expanding this important but understudied class of nongenomically encoded events for comprehensive characterization.}, } @article {pmid29294012, year = {2018}, author = {Baldwin-Brown, JG and Weeks, SC and Long, AD}, title = {A New Standard for Crustacean Genomes: The Highly Contiguous, Annotated Genome Assembly of the Clam Shrimp Eulimnadia texana Reveals HOX Gene Order and Identifies the Sex Chromosome.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {143-156}, pmid = {29294012}, issn = {1759-6653}, support = {R01 GM115562/GM/NIGMS NIH HHS/United States ; R01 OD010974/OD/NIH HHS/United States ; R21 AI126037/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Arthropod Proteins/*genetics ; Crustacea/*genetics ; Female ; Gene Order ; Genes, Homeobox ; Genetic Linkage ; Genome ; *Genomics/methods ; Homeodomain Proteins/*genetics ; Male ; Microsatellite Repeats ; Sex Chromosomes ; }, abstract = {Vernal pool clam shrimp (Eulimnadia texana) are a promising model system due to their ease of lab culture, short generation time, modest sized genome, a somewhat rare stable androdioecious sex determination system, and a requirement to reproduce via desiccated diapaused eggs. We generated a highly contiguous genome assembly using 46× of PacBio long read data and 216× of Illumina short reads, and annotated using Illumina RNAseq obtained from adult males or hermaphrodites. Of the 120 Mb genome 85% is contained in the largest eight contigs, the smallest of which is 4.6 Mb. The assembly contains 98% of transcripts predicted via RNAseq. This assembly is qualitatively different from scaffolded Illumina assemblies: It is produced from long reads that contain sequence data along their entire length, and is thus gap free. The contiguity of the assembly allows us to order the HOX genes within the genome, identifying two loci that contain HOX gene orthologs, and which approximately maintain the order observed in other arthropods. We identified a partial duplication of the Antennapedia complex adjacent to the few genes homologous to the Bithorax locus. Because the sex chromosome of an androdioecious species is of special interest, we used existing allozyme and microsatellite markers to identify the E. texana sex chromosome, and find that it comprises nearly half of the genome of this species. Linkage patterns indicate that recombination is extremely rare and perhaps absent in hermaphrodites, and as a result the location of the sex determining locus will be difficult to refine using recombination mapping.}, } @article {pmid29294010, year = {2018}, author = {Baldo, L and Riera, JL and Mitsi, K and Pretus, JL}, title = {Processes shaping gut microbiota diversity in allopatric populations of the endemic lizard Podarcis lilfordi from Menorcan islets (Balearic Islands).}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix186}, pmid = {29294010}, issn = {1574-6941}, abstract = {Compositional variation of the gut microbiota across host allopatric populations can reflect both adaptation and stochasticity since the time of separation. Major factors shaping this variation include the host phylogeographic and demographic history, the microbiota inheritance, environmental inputs and dispersal of bacteria. Here we explored the impact of these factors in driving gut community diversity in seven allopatric populations of the omnivorous lizard Podarcis lilfordi from the Menorcan coastal islets, all descending from an ancestral mainland population. Using 16S rRNA Illumina sequencing, we showed that 'islet' and 'age' (time since islet separation from mainland) were the only significant variables in microbial community clustering, suggesting a partial islet-restricted diversification following these lizards phylogeography. Despite a significant variation, islets/populations were characterized by a remarkably low bacterial uniqueness (2.4% of total OTUs) and a minor differential enrichment of taxa, indicating a negligible impact of local inputs and important host common constraints. Overall, the extant pattern of similarity/dissimilarity among islets is compatible with partial retention of the ancestral mainland microbial pool, with differences among islets potentially explained by a differential loss of bacteria following population fragmentation and bottlenecks (i.e. ecological drift). While more quantitative data are needed to validate this hypothesis, this study unveils the importance of considering both neutral and niche-driven processes in driving contemporary patterns of gut metacommunity diversity.}, } @article {pmid29294004, year = {2018}, author = {Nishihara, H and Stanyon, R and Kusumi, J and Hirai, H and Koga, A}, title = {Evolutionary Origin of OwlRep, a Megasatellite DNA Associated with Adaptation of Owl Monkeys to Nocturnal Lifestyle.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {157-165}, pmid = {29294004}, issn = {1759-6653}, mesh = {*Adaptation, Physiological ; Animals ; Aotidae/*genetics/physiology ; Base Sequence ; DNA, Satellite/*genetics ; *Evolution, Molecular ; Heterochromatin/genetics ; Night Vision ; Phylogeny ; Repetitive Sequences, Nucleic Acid ; }, abstract = {Rod cells of many nocturnal mammals have a "non-standard" nuclear architecture, which is called the inverted nuclear architecture. Heterochromatin localizes to the central region of the nucleus. This leads to an efficient light transmission to the outer segments of photoreceptors. Rod cells of diurnal mammals have the conventional nuclear architecture. Owl monkeys (genus Aotus) are the only taxon of simian primates that has a nocturnal or cathemeral lifestyle, and this adaptation is widely thought to be secondary. Their rod cells were shown to exhibit an intermediate chromatin distribution: a spherical heterochromatin block was found in the central region of the nucleus although it was less complete than that of typical nocturnal mammals. We recently demonstrated that the primary DNA component of this heterochromatin block was OwlRep, a megasatellite DNA consisting of 187-bp-long repeat units. However, the origin of OwlRep was not known. Here we show that OwlRep was derived from HSAT6, a simple repeat sequence found in the centromere regions of human chromosomes. HSAT6 occurs widely in primates, suggesting that it was already present in the last common ancestor of extant primates. Notably, Strepsirrhini and Tarsiformes apparently carry a single HSAT6 copy, whereas many species of Simiiformes contain multiple copies. Comparison of nucleotide sequences of these copies revealed the entire process of the OwlRep formation. HSAT6, with or without flanking sequences, was segmentally duplicated in New World monkeys. Then, in the owl monkey linage after its divergence from other New World monkeys, a copy of HSAT6 was tandemly amplified, eventually forming a megasatellite DNA.}, } @article {pmid29293993, year = {2018}, author = {Mäkinen, H and Sävilammi, T and Papakostas, S and Leder, E and Vøllestad, LA and Primmer, CR}, title = {Modularity Facilitates Flexible Tuning of Plastic and Evolutionary Gene Expression Responses during Early Divergence.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {77-93}, pmid = {29293993}, issn = {1759-6653}, mesh = {Acclimatization ; Animals ; *Biological Evolution ; *Gene Expression Regulation ; Gene Regulatory Networks ; Genetic Drift ; Genetics, Population ; Salmonidae/*genetics/physiology ; Selection, Genetic ; Temperature ; }, abstract = {Gene expression changes have been recognized as important drivers of adaptation to changing environmental conditions. Little is known about the relative roles of plastic and evolutionary responses in complex gene expression networks during the early stages of divergence. Large gene expression data sets coupled with in silico methods for identifying coexpressed modules now enable systems genetics approaches also in nonmodel species for better understanding of gene expression responses during early divergence. Here, we combined gene coexpression analyses with population genetics to separate plastic and population (evolutionary) effects in expression networks using small salmonid populations as a model system. We show that plastic and population effects were highly variable among the six identified modules and that the plastic effects explained larger proportion of the total eigengene expression than population effects. A more detailed analysis of the population effects using a QST - FST comparison across 16,622 annotated transcripts revealed that gene expression followed neutral expectations within modules and at the global level. Furthermore, two modules showed enrichment for genes coding for early developmental traits that have been previously identified as important phenotypic traits in thermal responses in the same model system indicating that coexpression analysis can capture expression patterns underlying ecologically important traits. We suggest that module-specific responses may facilitate the flexible tuning of expression levels to local thermal conditions. Overall, our study indicates that plasticity and neutral evolution are the main drivers of gene expression variance in the early stages of thermal adaptation in this system.}, } @article {pmid29293976, year = {2018}, author = {Verdes, A and Simpson, D and Holford, M}, title = {Are Fireworms Venomous? Evidence for the Convergent Evolution of Toxin Homologs in Three Species of Fireworms (Annelida, Amphinomidae).}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {249-268}, pmid = {29293976}, issn = {1759-6653}, support = {G12 MD007599/MD/NIMHD NIH HHS/United States ; UL1 TR000457/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Annelida/*genetics ; Cystatins/genetics ; Lectins, C-Type/genetics ; Lipocalins/genetics ; Neurotoxins/genetics ; Peptide Hydrolases/genetics ; Phospholipases/genetics ; Phylogeny ; Serpins/genetics ; *Transcriptome ; Venoms/*genetics ; }, abstract = {Amphinomids, more commonly known as fireworms, are a basal lineage of marine annelids characterized by the presence of defensive dorsal calcareous chaetae, which break off upon contact. It has long been hypothesized that amphinomids are venomous and use the chaetae to inject a toxic substance. However, studies investigating fireworm venom from a morphological or molecular perspective are scarce and no venom gland has been identified to date, nor any toxin characterized at the molecular level. To investigate this question, we analyzed the transcriptomes of three species of fireworms-Eurythoe complanata, Hermodice carunculata, and Paramphinome jeffreysii-following a venomics approach to identify putative venom compounds. Our venomics pipeline involved de novo transcriptome assembly, open reading frame, and signal sequence prediction, followed by three different homology search strategies: BLAST, HMMER sequence, and HMMER domain. Following this pipeline, we identified 34 clusters of orthologous genes, representing 13 known toxin classes that have been repeatedly recruited into animal venoms. Specifically, the three species share a similar toxin profile with C-type lectins, peptidases, metalloproteinases, spider toxins, and CAP proteins found among the most highly expressed toxin homologs. Despite their great diversity, the putative toxins identified are predominantly involved in three major biological processes: hemostasis, inflammatory response, and allergic reactions, all of which are commonly disrupted after fireworm stings. Although the putative fireworm toxins identified here need to be further validated, our results strongly suggest that fireworms are venomous animals that use a complex mixture of toxins for defense against predators.}, } @article {pmid29293959, year = {2018}, author = {Liang, Z and Siegert, M and Fang, W and Sun, Y and Jiang, F and Lu, H and Chen, GH and Wang, S}, title = {Blackening and odorization of urban rivers: a bio-geochemical process.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fix180}, pmid = {29293959}, issn = {1574-6941}, abstract = {Urban rivers constitute a major part of urban drainage systems, and play critical roles in connecting other surface waters in urban areas. Black-odorous urban rivers are widely found in developing countries experiencing rapid urbanization, and the mismatch between urbanization and sewage treatment is thought to be the reason. The phenomena of blackening and odorization are likely complex bio-geochemical processes of which the microbial interactions with the environment are not fully understood. Here, we provide an overview of the major chemical compounds, such as iron and sulfur, and their bio-geochemical conversions during blackening and odorization of urban rivers. Scenarios explaining the formation of black-odorous urban rivers are proposed. Finally, we point out knowledge gaps in mechanisms and microbial ecology that need to be addressed to better understand the development of black-odorous urban rivers.}, } @article {pmid29293955, year = {2018}, author = {Lai, JYH and Zhang, H and Chiang, MHY and Lun, CHI and Zhang, R and Lau, SCK}, title = {The putative functions of lysogeny in mediating the survivorship of Escherichia coli in seawater and marine sediment.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix187}, pmid = {29293955}, issn = {1574-6941}, abstract = {Escherichia coli colonizes various body parts of animal hosts as a commensal and a pathogen. It can also persist in the external environment in the absence of fecal pollution. It remains unclear how this species has evolved to adapt to such contrasting habitats. Lysogeny plays pivotal roles in the diversification of the phenotypic and ecologic characters of E. coli as a symbiont. We hypothesized that lysogeny could also confer fitness to survival in the external environment. To test this hypothesis, we used the induced phages of an E. coli strain originating from marine sediment to infect a fecal E. coli strain to obtain an isogenic lysogen of the latter. The three strains were tested for survivorship in microcosms of seawater, marine sediment and sediment interstitial water as well as swimming motility, glycogen accumulation, biofilm formation, substrate utilization and stress resistance. The results indicate that lysogenic infection led to tractable changes in many of the ecophysiological attributes tested. Particularly, the lysogen had better survivorship in the microcosms and had a substrate utilization profile resembling the sediment strain more than the wild type fecal strain. Our findings provide new insights into the understanding of how E. coli survives in the natural environment.}, } @article {pmid29292690, year = {2018}, author = {Oren, A and Garrity, GM}, title = {List of new names and new combinations previously effectively, but not validly, published.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {1-2}, doi = {10.1099/ijsem.0.002501}, pmid = {29292690}, issn = {1466-5034}, } @article {pmid29292689, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification that new names of prokaryotes, new combinations and new taxonomic opinions have appeared in volume 67, part 10, of the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {3-6}, doi = {10.1099/ijsem.0.002462}, pmid = {29292689}, issn = {1466-5034}, } @article {pmid29292688, year = {2018}, author = {Oren, A and Garrity, GM}, title = {Notification of changes in taxonomic opinion previously published outside the IJSEM.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {7-8}, doi = {10.1099/ijsem.0.002502}, pmid = {29292688}, issn = {1466-5034}, } @article {pmid29292687, year = {2018}, author = {Chun, J and Oren, A and Ventosa, A and Christensen, H and Arahal, DR and da Costa, MS and Rooney, AP and Yi, H and Xu, XW and De Meyer, S and Trujillo, ME}, title = {Proposed minimal standards for the use of genome data for the taxonomy of prokaryotes.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {461-466}, doi = {10.1099/ijsem.0.002516}, pmid = {29292687}, issn = {1466-5034}, mesh = {Genomics/*standards ; *Phylogeny ; Prokaryotic Cells/*classification ; Sequence Analysis, DNA/*standards ; Terminology as Topic ; }, abstract = {Advancement of DNA sequencing technology allows the routine use of genome sequences in the various fields of microbiology. The information held in genome sequences proved to provide objective and reliable means in the taxonomy of prokaryotes. Here, we describe the minimal standards for the quality of genome sequences and how they can be applied for taxonomic purposes.}, } @article {pmid29292397, year = {2018}, author = {Long, H and Sung, W and Kucukyildirim, S and Williams, E and Miller, SF and Guo, W and Patterson, C and Gregory, C and Strauss, C and Stone, C and Berne, C and Kysela, D and Shoemaker, WR and Muscarella, ME and Luo, H and Lennon, JT and Brun, YV and Lynch, M}, title = {Evolutionary determinants of genome-wide nucleotide composition.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {237-240}, doi = {10.1038/s41559-017-0425-y}, pmid = {29292397}, issn = {2397-334X}, support = {R01 GM036827/GM/NIGMS NIH HHS/United States ; R01 GM101672/GM/NIGMS NIH HHS/United States ; R35 GM122566/GM/NIGMS NIH HHS/United States ; }, abstract = {One of the long-standing mysteries of evolutionary genomics is the source of the wide phylogenetic diversity in genome nucleotide composition (G + C versus A + T), which must be a consequence of interspecific differences in mutation bias, the efficiency of selection for different nucleotides or a combination of the two. We demonstrate that although genomic G + C composition is strongly driven by mutation bias, it is also substantially modified by direct selection and/or as a by-product of biased gene conversion. Moreover, G + C composition at fourfold redundant sites is consistently elevated above the neutral expectation-more so than for any other class of sites.}, } @article {pmid29292396, year = {2018}, author = {Kaya, F and Bibi, F and Žliobaitė, I and Eronen, JT and Hui, T and Fortelius, M}, title = {The rise and fall of the Old World savannah fauna and the origins of the African savannah biome.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {241-246}, doi = {10.1038/s41559-017-0414-1}, pmid = {29292396}, issn = {2397-334X}, abstract = {Despite much interest in the ecology and origins of the extensive grassland ecosystems of the modern world, the biogeographic relationships of savannah palaeobiomes of Africa, India and mainland Eurasia have remained unclear. Here we assemble the most recent data from the Neogene mammal fossil record in order to map the biogeographic development of Old World mammalian faunas in relation to palaeoenvironmental conditions. Using genus-level faunal similarity and mean ordinated hypsodonty in combination with palaeoclimate modelling, we show that savannah faunas developed as a spatially and temporally connected entity that we term the Old World savannah palaeobiome. The Old World savannah palaeobiome flourished under the influence of middle and late Miocene global cooling and aridification, which resulted in the spread of open habitats across vast continental areas. This extensive biome fragmented into Eurasian and African branches due to increased aridification in North Africa and Arabia during the late Miocene. Its Eurasian branches had mostly disappeared by the end of the Miocene, but the African branch survived and eventually contributed to the development of Plio-Pleistocene African savannah faunas, including their early hominins. The modern African savannah fauna is thus a continuation of the extensive Old World savannah palaeobiome.}, } @article {pmid29292395, year = {2018}, author = {Cote, S}, title = {Savannah savvy.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {210-211}, doi = {10.1038/s41559-017-0450-x}, pmid = {29292395}, issn = {2397-334X}, } @article {pmid29292390, year = {2018}, author = {Du Toit, A}, title = {Parasite biology: Keeping Plasmodium awake.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {63}, pmid = {29292390}, issn = {1740-1534}, } @article {pmid29292389, year = {2018}, author = {York, A}, title = {Viral infection: A fungus boosts dengue virus in the mosquito gut.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {64-65}, pmid = {29292389}, issn = {1740-1534}, } @article {pmid29292388, year = {2018}, author = {Pike, LJ and Viciani, E and Kumar, N}, title = {Genome watch: Microbial diversity knows no borders.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {66}, pmid = {29292388}, issn = {1740-1534}, } @article {pmid29292387, year = {2018}, author = {Turley, P and Walters, RK and Maghzian, O and Okbay, A and Lee, JJ and Fontana, MA and Nguyen-Viet, TA and Wedow, R and Zacher, M and Furlotte, NA and Magnusson, P and Oskarsson, S and Johannesson, M and Visscher, PM and Laibson, D and Cesarini, D and Neale, BM and Benjamin, DJ and , and , }, title = {Multi-trait analysis of genome-wide association summary statistics using MTAG.}, journal = {Nature genetics}, volume = {50}, number = {2}, pages = {229-237}, pmid = {29292387}, issn = {1546-1718}, support = {P01 HD031921/HD/NICHD NIH HHS/United States ; R01 HD060726/HD/NICHD NIH HHS/United States ; MC_QA137853//Medical Research Council/United Kingdom ; R01 HD073342/HD/NICHD NIH HHS/United States ; R01 MH107649/MH/NIMH NIH HHS/United States ; U01 MH109539/MH/NIMH NIH HHS/United States ; P30 AG034532/AG/NIA NIH HHS/United States ; R01 MH101244/MH/NIMH NIH HHS/United States ; P01 AG005842/AG/NIA NIH HHS/United States ; P30 AG012810/AG/NIA NIH HHS/United States ; R01 AG042568/AG/NIA NIH HHS/United States ; T32 AG000186/AG/NIA NIH HHS/United States ; 647648//European Research Council/International ; }, abstract = {We introduce multi-trait analysis of GWAS (MTAG), a method for joint analysis of summary statistics from genome-wide association studies (GWAS) of different traits, possibly from overlapping samples. We apply MTAG to summary statistics for depressive symptoms (N eff = 354,862), neuroticism (N = 168,105), and subjective well-being (N = 388,538). As compared to the 32, 9, and 13 genome-wide significant loci identified in the single-trait GWAS (most of which are themselves novel), MTAG increases the number of associated loci to 64, 37, and 49, respectively. Moreover, association statistics from MTAG yield more informative bioinformatics analyses and increase the variance explained by polygenic scores by approximately 25%, matching theoretical expectations.}, } @article {pmid29292384, year = {2018}, author = {Chen, J and Sathiyamoorthy, K and Zhang, X and Schaller, S and Perez White, BE and Jardetzky, TS and Longnecker, R}, title = {Ephrin receptor A2 is a functional entry receptor for Epstein-Barr virus.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {172-180}, pmid = {29292384}, issn = {2058-5276}, support = {R01 AI076183/AI/NIAID NIH HHS/United States ; R01 AI137267/AI/NIAID NIH HHS/United States ; R01 CA117794/CA/NCI NIH HHS/United States ; R21 AI119480/AI/NIAID NIH HHS/United States ; }, abstract = {Epstein-Barr virus (EBV) is an oncogenic virus that infects more than 90% of the world's population 1 . EBV predominantly infects human B cells and epithelial cells, which is initiated by fusion of the viral envelope with a host cellular membrane 2 . The mechanism of EBV entry into B cells has been well characterized 3 . However, the mechanism for epithelial cell entry remains elusive. Here, we show that the integrins αvβ5, αvβ6 and αvβ8 do not function as entry and fusion receptors for epithelial cells, whereas Ephrin receptor tyrosine kinase A2 (EphA2) functions well for both. EphA2 overexpression significantly increased EBV infection of HEK293 cells. Using a virus-free cell-cell fusion assay, we found that EphA2 dramatically promoted EBV but not herpes simplex virus (HSV) fusion with HEK293 cells. EphA2 silencing using small hairpin RNA (shRNA) or knockout by CRISPR-Cas9 blocked fusion with epithelial cells. This inhibitory effect was rescued by the expression of EphA2. Antibody against EphA2 blocked epithelial cell infection. Using label-free surface plasmon resonance binding studies, we confirmed that EphA2 but not EphA4 specifically bound to EBV gHgL and this interaction is through the EphA2 extracellular domain (ECD). The discovery of EphA2 as an EBV epithelial cell receptor has important implications for EBV pathogenesis and may uncover new potential targets that can be used for the development of novel intervention strategies.}, } @article {pmid29292383, year = {2018}, author = {Zhang, H and Li, Y and Wang, HB and Zhang, A and Chen, ML and Fang, ZX and Dong, XD and Li, SB and Du, Y and Xiong, D and He, JY and Li, MZ and Liu, YM and Zhou, AJ and Zhong, Q and Zeng, YX and Kieff, E and Zhang, Z and Gewurz, BE and Zhao, B and Zeng, MS}, title = {Ephrin receptor A2 is an epithelial cell receptor for Epstein-Barr virus entry.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {1-8}, doi = {10.1038/s41564-017-0080-8}, pmid = {29292383}, issn = {2058-5276}, abstract = {Epstein-Barr virus (EBV) is causally associated with nasopharyngeal carcinoma, 10% of gastric carcinoma and various B cell lymphomas 1 . EBV infects both B cells and epithelial cells 2 . Recently, we reported that epidermal growth factor and Neuropilin 1 markedly enhanced EBV entry into nasopharyngeal epithelial cells 3 . However, knowledge of how EBV infects epithelial cells remains incomplete. To understand the mechanisms through which EBV infects epithelial cells, we integrated microarray and RNA interference screen analyses and found that Ephrin receptor A2 (EphA2) is important for EBV entry into the epithelial cells. EphA2 short interfering RNA knockdown or CRISPR-Cas9 knockout markedly reduced EBV epithelial cell infection, which was mostly restored by EphA2 complementary DNA rescue. EphA2 overexpression increased epithelial cell EBV infection. Soluble EphA2 protein, antibodies against EphA2, soluble EphA2 ligand EphrinA1, or the EphA2 inhibitor 2,5-dimethylpyrrolyl benzoic acid efficiently blocked EBV epithelial cell infection. Mechanistically, EphA2 interacted with EBV entry proteins gH/gL and gB to facilitate EBV internalization and fusion. The EphA2 Ephrin-binding domain and fibronectin type III repeats domain were essential for EphA2-mediated EBV infection, while the intracellular domain was dispensable. This is distinct from Kaposi's sarcoma-associated herpesvirus infection through EphA2 4 . Taken together, our results identify EphA2 as a critical player for EBV epithelial cell entry.}, } @article {pmid29291984, year = {2018}, author = {Sato, K and Umesono, Y and Mochii, M}, title = {A transgenic reporter under control of an es1 promoter/enhancer marks wound epidermis and apical epithelial cap during tail regeneration in Xenopus laevis tadpole.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {404-415}, doi = {10.1016/j.ydbio.2017.08.012}, pmid = {29291984}, issn = {1095-564X}, mesh = {Amputation ; Animals ; Animals, Genetically Modified ; Carboxylesterase/*genetics ; Drug Evaluation, Preclinical ; Enhancer Elements, Genetic/*genetics ; Epidermal Cells ; Epidermis/*physiology ; Gene Expression Regulation ; *Genes, Reporter ; Green Fluorescent Proteins/analysis/*genetics ; Larva ; Promoter Regions, Genetic/*genetics ; Recombinant Fusion Proteins/genetics/metabolism ; Regeneration/*physiology ; Signal Transduction ; Tail/injuries/*physiology ; *Transgenes ; Wound Healing/drug effects/physiology ; Xenopus Proteins/genetics/*physiology ; Xenopus laevis/genetics/growth & development/*physiology ; }, abstract = {Rapid wound healing and subsequent formation of the apical epithelial cap (AEC) are believed to be required for successful appendage regeneration in amphibians. Despite the significant role of AEC in limb regeneration, its role in tail regeneration and the mechanisms that regulate the wound healing and AEC formation are not well understood. We previously identified Xenopus laevis es1, which is preferentially expressed in wounded regions, including the AEC after tail regeneration. In this study we established and characterized transgenic Xenopus laevis lines harboring the enhanced green fluorescent protein (EGFP) gene under control of an es1 gene regulatory sequence (es1:egfp). The EGFP reporter expression was clearly seen in several regions of the embryo and then declined to an undetectable level in larvae, recapitulating the endogenous es1 expression. After amputation of the tadpole tail, EGFP expression was re-activated at the edge of the stump epidermis and then increased in the wound epidermis (WE) covering the amputation surface. As the stump started to regenerate, the EGFP expression became restricted to the most distal epidermal region, including the AEC. EGFP was preferentially expressed in the basal or deep cells but not in the superficial cells of the WE and AEC. We performed a small-scale pharmacological screening for chemicals that affected the expression of EGFP in the stump epidermis after tail amputation. The EGFP expression was attenuated by treatment with an inhibitor for ERK, TGF-β or reactive oxygen species (ROS) signaling. These treatments also impaired wound closure of the amputation surface, suggesting that the three signaling activities are required for es1 expression in the WE and successful wound healing after tail amputation. These findings showed that es1:egfp Xenopus laevis should be a useful tool to analyze molecular mechanisms regulating wound healing and appendage regeneration.}, } @article {pmid29291983, year = {2018}, author = {Echeverri-Ruiz, N and Haynes, T and Landers, J and Woods, J and Gemma, MJ and Hughes, M and Del Rio-Tsonis, K}, title = {A biochemical basis for induction of retina regeneration by antioxidants.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {394-403}, pmid = {29291983}, issn = {1095-564X}, support = {R01 EY026816/EY/NEI NIH HHS/United States ; R21 EY023925/EY/NEI NIH HHS/United States ; }, mesh = {Acetylcysteine/*pharmacology ; Animals ; Antioxidants/*pharmacology ; Cell Differentiation/drug effects ; Chick Embryo ; Ciliary Body/cytology ; Disulfides/metabolism ; Fibroblast Growth Factor 2/pharmacology ; Glutathione/metabolism ; Glutathione Peroxidase/metabolism ; MAP Kinase Signaling System/drug effects ; Oxidation-Reduction ; Regeneration/*drug effects/physiology ; Retina/drug effects/*physiology ; Stem Cells/cytology/*drug effects ; Sulfhydryl Compounds/metabolism ; }, abstract = {The use of antioxidants in tissue regeneration has been studied, but their mechanism of action is not well understood. Here, we analyze the role of the antioxidant N-acetylcysteine (NAC) in retina regeneration. Embryonic chicks are able to regenerate their retina after its complete removal from retinal stem/progenitor cells present in the ciliary margin (CM) of the eye only if a source of exogenous factors, such as FGF2, is present. This study shows that NAC modifies the redox status of the CM, initiates self-renewal of the stem/progenitor cells, and induces regeneration in the absence of FGF2. NAC works as an antioxidant by scavenging free radicals either independently or through the synthesis of glutathione (GSH), and/or by reducing oxidized proteins through a thiol disulfide exchange activity. We dissected the mechanism used by NAC to induce regeneration through the use of inhibitors of GSH synthesis and the use of other antioxidants with different biochemical structures and modes of action, and found that NAC induces regeneration through its thiol disulfide exchange activity. Thus, our results provide, for the first time, a biochemical basis for induction of retina regeneration. Furthermore, NAC induction was independent of FGF receptor signaling, but dependent on the MAPK (pErk1/2) pathway.}, } @article {pmid29291982, year = {2018}, author = {Kawamura, K and Yoshida, T and Sekida, S}, title = {Autophagic dedifferentiation induced by cooperation between TOR inhibitor and retinoic acid signals in budding tunicates.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {384-393}, doi = {10.1016/j.ydbio.2017.08.023}, pmid = {29291982}, issn = {1095-564X}, mesh = {Animals ; Autophagosomes/physiology ; Autophagy/*drug effects ; Autophagy-Related Protein 7/genetics/metabolism ; Cell Dedifferentiation/*drug effects ; Cell Transdifferentiation/*drug effects ; Exosomes/physiology ; Gene Expression Regulation, Developmental/drug effects ; Indoles/pharmacology ; Lysosomes/physiology ; Mitochondria/physiology ; Proton Pumps/genetics/metabolism ; Purines/pharmacology ; Reproduction, Asexual ; Retinoid X Receptors/physiology ; Sirolimus/pharmacology ; TOR Serine-Threonine Kinases/*antagonists & inhibitors/physiology ; Tretinoin/*pharmacology ; Urochordata/drug effects/*physiology ; }, abstract = {Asexual bud development in the budding tunicate Polyandrocarpa misakiensis involves transdifferentiation of multipotent epithelial cells, which is triggered by retinoic acid (RA), and thrives under starvation after bud isolation from the parent. This study aimed to determine cell and molecular mechanisms of dedifferentiation that occur during the early stage of transdifferentiation. During dedifferentiation, the numbers of autophagosomes, lysosomes, and secondary lysosomes increased remarkably. Mitochondrial degradation and exosome discharge also occurred in the atrial epithelium. Autophagy-related gene 7 (Atg7) and lysosomal proton pump A gene (PumpA) were activated during the dedifferentiation stage. When target of rapamycin (TOR) inhibitor was administered to growing buds without isolating them from the parent, phagosomes and secondary lysosomes became prominent. TOR inhibitor induced Atg7 only in the presence of RA. In contrast, when growing buds were treated with RA, lysosomes, secondary lysosomes, and mitochondrial degradation were prematurely induced. RA significantly activated PumpA in a retinoid X receptor-dependent manner. Our results indicate that in P. misakiensis, TOR inhibition and RA signals act in synergy to accomplish cytoplasmic clearance for dedifferentiation.}, } @article {pmid29291981, year = {2018}, author = {Brown, DDR and Molinaro, AM and Pearson, BJ}, title = {The planarian TCF/LEF factor Smed-tcf1 is required for the regeneration of dorsal-lateral neuronal subtypes.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {374-383}, doi = {10.1016/j.ydbio.2017.08.024}, pmid = {29291981}, issn = {1095-564X}, mesh = {Animals ; GABAergic Neurons/physiology ; Ganglia, Invertebrate/physiology ; Gene Expression Regulation ; Genes, Helminth ; Genetic Association Studies ; Head/physiology ; Helminth Proteins/genetics/*physiology ; Nerve Regeneration/genetics/*physiology ; Nerve Tissue Proteins/*physiology ; Neurons/*physiology ; Organ Specificity ; Phototaxis ; Planarians/genetics/*physiology ; TCF Transcription Factors/*physiology ; Tail/physiology ; Transcriptome ; }, abstract = {The adult brain of the planarian Schmidtea mediterranea (a freshwater flatworm) is a dynamic structure with constant cell turnover as well as the ability to completely regenerate de novo. Despite this, function and pattern is achieved in a reproducible manner from individual to individual in terms of the correct spatial and temporal production of specific neuronal subtypes. Although several signaling molecules have been found to be key to scaling and cell turnover, the mechanisms by which specific neural subtypes are specified remain largely unknown. Here we performed a 6 day RNAseq time course on planarians that were regenerating either 0, 1, or 2 heads in order to identify novel regulators of brain regeneration. Focusing on transcription factors, we identified a TCF/LEF factor, Smed-tcf1, which was required to correctly pattern the dorsal-lateral cell types of the regenerating brain. The most severely affected neurons in Smed-tcf1(RNAi) animals were the dorsal GABAergic neurons, which failed to regenerate, leading to an inability of the animals to phototaxis away from light. Together, Smed-tcf1 is a critical regulator, required to pattern the dorsal-lateral region of the regenerating planarian brain.}, } @article {pmid29291980, year = {2018}, author = {Palade, J and Djordjevic, D and Hutchins, ED and George, RM and Cornelius, JA and Rawls, A and Ho, JWK and Kusumi, K and Wilson-Rawls, J}, title = {Identification of satellite cells from anole lizard skeletal muscle and demonstration of expanded musculoskeletal potential.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {344-356}, pmid = {29291980}, issn = {1095-564X}, support = {R21 AR064935/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Bone Morphogenetic Protein 2/genetics/physiology ; Cell Lineage ; Cells, Cultured ; Chondrogenesis/genetics ; Gene Expression Regulation ; Gene Ontology ; Humans ; Intracellular Signaling Peptides and Proteins/genetics/physiology ; Lizards/*physiology ; Mice ; Muscle Development/genetics ; Muscle Proteins/genetics/physiology ; Muscle, Skeletal/*cytology/physiology ; Myoblasts/cytology ; PAX7 Transcription Factor/analysis ; Satellite Cells, Skeletal Muscle/*physiology ; Signal Transduction ; Species Specificity ; Transcriptome ; }, abstract = {The lizards are evolutionarily the closest vertebrates to humans that demonstrate the ability to regenerate entire appendages containing cartilage, muscle, skin, and nervous tissue. We previously isolated PAX7-positive cells from muscle of the green anole lizard, Anolis carolinensis, that can differentiate into multinucleated myotubes and express the muscle structural protein, myosin heavy chain. Studying gene expression in these satellite/progenitor cell populations from A. carolinensis can provide insight into the mechanisms regulating tissue regeneration. We generated a transcriptome from proliferating lizard myoprogenitor cells and compared them to transcriptomes from the mouse and human tissues from the ENCODE project using XGSA, a statistical method for cross-species gene set analysis. These analyses determined that the lizard progenitor cell transcriptome was most similar to mammalian satellite cells. Further examination of specific GO categories of genes demonstrated that among genes with the highest level of expression in lizard satellite cells were an increased number of genetic regulators of chondrogenesis, as compared to mouse satellite cells. In micromass culture, lizard PAX7-positive cells formed Alcian blue and collagen 2a1 positive nodules, without the addition of exogenous morphogens, unlike their mouse counterparts. Subsequent quantitative RT-PCR confirmed up-regulation of expression of chondrogenic regulatory genes in lizard cells, including bmp2, sox9, runx2, and cartilage specific structural genes, aggrecan and collagen 2a1. Taken together, these data suggest that tail regeneration in lizards involves significant alterations in gene regulation with expanded musculoskeletal potency.}, } @article {pmid29291979, year = {2018}, author = {Ferrario, C and Ben Khadra, Y and Czarkwiani, A and Zakrzewski, A and Martinez, P and Colombo, G and Bonasoro, F and Candia Carnevali, MD and Oliveri, P and Sugni, M}, title = {Fundamental aspects of arm repair phase in two echinoderm models.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {297-309}, doi = {10.1016/j.ydbio.2017.09.035}, pmid = {29291979}, issn = {1095-564X}, support = {099745/Z/12/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Collagen/metabolism ; Epidermis/ultrastructure ; Extracellular Matrix Proteins/metabolism ; Extremities/*physiology ; Gene Expression Regulation ; Genetic Association Studies ; Microscopy, Electron ; Regeneration/genetics/immunology/*physiology ; Species Specificity ; Starfish/genetics/immunology/*physiology ; Transcription Factors/physiology ; Wound Healing/physiology ; }, abstract = {Regeneration is a post-embryonic developmental process that ensures complete morphological and functional restoration of lost body parts. The repair phase is a key step for the effectiveness of the subsequent regenerative process: in vertebrates, efficient re-epithelialisation, rapid inflammatory/immune response and post-injury tissue remodelling are fundamental aspects for the success of this phase, their impairment leading to an inhibition or total prevention of regeneration. Among deuterostomes, echinoderms display a unique combination of striking regenerative abilities and diversity of useful experimental models, although still largely unexplored. Therefore, the brittle star Amphiura filiformis and the starfish Echinaster sepositus were here used to comparatively investigate the main repair phase events after injury as well as the presence and expression of immune system and extracellular matrix (i.e. collagen) molecules using both microscopy and molecular tools. Our results showed that emergency reaction and re-epithelialisation are similar in both echinoderm models, being faster and more effective than in mammals. Moreover, in comparison to the latter, both echinoderms showed delayed and less abundant collagen deposition at the wound site (absence of fibrosis). The gene expression patterns of molecules related to the immune response, such as Ese-fib-like (starfishes) and Afi-ficolin (brittle stars), were described for the first time during echinoderm regeneration providing promising starting points to investigate the immune system role in these regeneration models. Overall, the similarities in repair events and timing within the echinoderms and the differences with what has been reported in mammals suggest that effective repair processes in echinoderms play an important role for their subsequent ability to regenerate. Targeted molecular and functional analyses will shed light on the evolution of these abilities in the deuterostomian lineage.}, } @article {pmid29291978, year = {2018}, author = {Tokuyama, MA and Xu, C and Fisher, RE and Wilson-Rawls, J and Kusumi, K and Newbern, JM}, title = {Developmental and adult-specific processes contribute to de novo neuromuscular regeneration in the lizard tail.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {287-296}, pmid = {29291978}, issn = {1095-564X}, support = {R00 NS076661/NS/NINDS NIH HHS/United States ; R01 NS097537/NS/NINDS NIH HHS/United States ; R21 AR064935/AR/NIAMS NIH HHS/United States ; R21 RR031305/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Axons/physiology ; Bungarotoxins/pharmacology ; Fluorescent Dyes ; Lizards/*physiology ; Motor Neurons/physiology ; Muscle, Skeletal/physiology ; Myelin Sheath/physiology ; Nerve Regeneration ; Neuromuscular Junction/physiology ; Regeneration/*physiology ; Schwann Cells/physiology ; Tail/innervation/*physiology ; }, abstract = {Peripheral nerves exhibit robust regenerative capabilities in response to selective injury among amniotes, but the regeneration of entire muscle groups following volumetric muscle loss is limited in birds and mammals. In contrast, lizards possess the remarkable ability to regenerate extensive de novo muscle after tail loss. However, the mechanisms underlying reformation of the entire neuromuscular system in the regenerating lizard tail are not completely understood. We have tested whether the regeneration of the peripheral nerve and neuromuscular junctions (NMJs) recapitulate processes observed during normal neuromuscular development in the green anole, Anolis carolinensis. Our data confirm robust axonal outgrowth during early stages of tail regeneration and subsequent NMJ formation within weeks of autotomy. Interestingly, NMJs are overproduced as evidenced by a persistent increase in NMJ density 120 and 250 days post autotomy (DPA). Substantial Myelin Basic Protein (MBP) expression could also be detected along regenerating nerves indicating that the ability of Schwann cells to myelinate newly formed axons remained intact. Overall, our data suggest that the mechanism of de novo nerve and NMJ reformation parallel, in part, those observed during neuromuscular development. However, the prolonged increase in NMJ number and aberrant muscle differentiation hint at processes specific to the adult response. An examination of the coordinated exchange between peripheral nerves, Schwann cells, and newly synthesized muscle of the regenerating neuromuscular system may assist in the identification of candidate molecules that promote neuromuscular recovery in organisms incapable of a robust regenerative response.}, } @article {pmid29291977, year = {2018}, author = {Mitogawa, K and Makanae, A and Satoh, A}, title = {Hyperinnervation improves Xenopus laevis limb regeneration.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {276-286}, doi = {10.1016/j.ydbio.2017.10.007}, pmid = {29291977}, issn = {1095-564X}, mesh = {Amputation ; Animals ; Cells, Cultured ; Denervation ; Extremities/innervation/*physiology ; *Gene Expression Regulation ; *Nerve Transfer ; Predatory Behavior ; Regeneration/genetics/*physiology ; Sciatic Nerve/injuries/physiology ; Swimming ; Wound Healing/genetics/physiology ; Xenopus Proteins/biosynthesis/genetics ; Xenopus laevis/genetics/*physiology ; }, abstract = {Xenopus laevis (an anuran amphibian) shows limb regeneration ability between that of urodele amphibians and that of amniotes. Xenopus frogs can initiate limb regeneration but fail to form patterned limbs. Regenerated limbs mainly consist of cone-shaped cartilage without any joints or branches. These pattern defects are thought to be caused by loss of proper expressions of patterning-related genes. This study shows that hyperinnervation surgery resulted in the induction of a branching regenerate. The hyperinnervated blastema allows the identification and functional analysis of the molecules controlling this patterning of limb regeneration. This paper focuses on the nerve affects to improve Xenopus limb patterning ability during regeneration. The nerve molecules, which regulate limb patterning, were also investigated. Blastemas grown in a hyperinnervated forelimb upregulate limb patterning-related genes (shh, lmx1b, and hoxa13). Nerves projecting their axons to limbs express some growth factors (bmp7, fgf2, fgf8, and shh). Inputs of these factors to a blastema upregulated some limb patterning-related genes and resulted in changes in the cartilage patterns in the regenerates. These results indicate that additional nerve factors enhance Xenopus limb patterning-related gene expressions and limb regeneration ability, and that bmp, fgf, and shh are candidate nerve substitute factors.}, } @article {pmid29291976, year = {2018}, author = {Buzgariu, W and Wenger, Y and Tcaciuc, N and Catunda-Lemos, AP and Galliot, B}, title = {Impact of cycling cells and cell cycle regulation on Hydra regeneration.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {240-253}, doi = {10.1016/j.ydbio.2017.11.003}, pmid = {29291976}, issn = {1095-564X}, mesh = {Animals ; Cell Cycle/genetics/*physiology ; Cell Division ; Flow Cytometry ; Gene Expression Profiling ; Gene Expression Regulation ; Genes, cdc ; Hydra/cytology/drug effects/genetics/*physiology ; Hydroxyurea/pharmacology ; Nocodazole/pharmacology ; Regeneration/drug effects/genetics/*physiology ; S Phase ; Stem Cells/*physiology ; Transcriptome ; }, abstract = {Hydra tissues are made from three distinct populations of stem cells that continuously cycle and pause in G2 instead of G1. To characterize the role of cell proliferation after mid-gastric bisection, we have (i) used flow cytometry and classical markers to monitor cell cycle modulations, (ii) quantified the transcriptomic regulations of 202 genes associated with cell proliferation during head and foot regeneration, and (iii) compared the impact of anti-proliferative treatments on regeneration efficiency. We confirm two previously reported events: an early mitotic wave in head-regenerating tips, when few cell cycle genes are up-regulated, and an early-late wave of proliferation on the second day, preceded by the up-regulation of 17 cell cycle genes. These regulations appear more intense after mid-gastric bisection than after decapitation, suggesting a position-dependent regulation of cell proliferation during head regeneration. Hydroxyurea, which blocks S-phase progression, delays head regeneration when applied before but not after bisection. This result is consistent with the fact that the Hydra central region is enriched in G2-paused adult stem cells, poised to divide upon injury, thus forming a necessary constitutive pro-blastema. However a prolonged exposure to hydroxyurea does not block regeneration as cells can differentiate apical structures without traversing S-phase, and also escape in few days the hydroxyurea-induced S-phase blockade. Thus Hydra head regeneration, which is a fast event, is highly plastic, relying on large stocks of adult stem cells paused in G2 at amputation time, which immediately divide to proliferate and/or differentiate apical structures even when S-phase is blocked.}, } @article {pmid29291975, year = {2018}, author = {Caballero-Pérez, J and Espinal-Centeno, A and Falcon, F and García-Ortega, LF and Curiel-Quesada, E and Cruz-Hernández, A and Bako, L and Chen, X and Martínez, O and Alberto Arteaga-Vázquez, M and Herrera-Estrella, L and Cruz-Ramírez, A}, title = {Transcriptional landscapes of Axolotl (Ambystoma mexicanum).}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {227-239}, doi = {10.1016/j.ydbio.2017.08.022}, pmid = {29291975}, issn = {1095-564X}, mesh = {Ambystoma mexicanum/*genetics/physiology ; Animals ; Female ; *Gene Expression Regulation ; Gene Library ; Gene Ontology ; Humans ; MicroRNAs/biosynthesis/genetics ; Organ Specificity ; Principal Component Analysis ; RNA, Messenger/biosynthesis/*genetics ; RNA, Small Interfering/genetics ; Regeneration/*genetics ; Sequence Analysis, RNA ; Species Specificity ; *Transcription, Genetic ; *Transcriptome ; }, abstract = {The axolotl (Ambystoma mexicanum) is the vertebrate model system with the highest regeneration capacity. Experimental tools established over the past 100 years have been fundamental to start unraveling the cellular and molecular basis of tissue and limb regeneration. In the absence of a reference genome for the Axolotl, transcriptomic analysis become fundamental to understand the genetic basis of regeneration. Here we present one of the most diverse transcriptomic data sets for Axolotl by profiling coding and non-coding RNAs from diverse tissues. We reconstructed a population of 115,906 putative protein coding mRNAs as full ORFs (including isoforms). We also identified 352 conserved miRNAs and 297 novel putative mature miRNAs. Systematic enrichment analysis of gene expression allowed us to identify tissue-specific protein-coding transcripts. We also found putative novel and conserved microRNAs which potentially target mRNAs which are reported as important disease candidates in heart and liver.}, } @article {pmid29291974, year = {2018}, author = {Strand, NS and Allen, JM and Ghulam, M and Taylor, MR and Munday, RK and Carrillo, M and Movsesyan, A and Zayas, RM}, title = {Dissecting the function of Cullin-RING ubiquitin ligase complex genes in planarian regeneration.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {210-217}, doi = {10.1016/j.ydbio.2017.10.011}, pmid = {29291974}, issn = {1095-564X}, mesh = {Animals ; Cullin Proteins/genetics/*physiology ; F-Box Motifs ; F-Box Proteins/*physiology ; Gene Expression Regulation ; Genes, Helminth ; Genetic Pleiotropy ; Helminth Proteins/*physiology ; Multiprotein Complexes ; Phenotype ; Planarians/genetics/*physiology ; RNA Interference ; RNA, Double-Stranded/genetics ; RNA, Helminth/genetics ; RNA, Small Interfering/genetics ; Regeneration/*physiology ; Stem Cells/physiology ; Ubiquitin/physiology ; Ubiquitin-Protein Ligases/*physiology ; }, abstract = {The ubiquitin system plays a role in nearly every aspect of eukaryotic cell biology. The enzymes responsible for transferring ubiquitin onto specific substrates are the E3 ubiquitin ligases, a large and diverse family of proteins, for which biological roles and target substrates remain largely undefined. Studies using model organisms indicate that ubiquitin signaling mediates key steps in developmental processes and tissue regeneration. Here, we used the freshwater planarian, Schmidtea mediterranea, to investigate the role of Cullin-RING ubiquitin ligase (CRL) complexes in stem cell regulation during regeneration. We identified six S. mediterranea cullin genes, and used RNAi to uncover roles for homologs of Cullin-1, -3 and -4 in planarian regeneration. The cullin-1 RNAi phenotype included defects in blastema formation, organ regeneration, lesions, and lysis. To further investigate the function of cullin-1-mediated cellular processes in planarians, we examined genes encoding the adaptor protein Skp1 and F-box substrate-recognition proteins that are predicted to partner with Cullin-1. RNAi against skp1 resulted in phenotypes similar to cullin-1 RNAi, and an RNAi screen of the F-box genes identified 19 genes that recapitulated aspects of cullin-1 RNAi, including ones that in mammals are involved in stem cell regulation and cancer biology. Our data provides evidence that CRLs play discrete roles in regenerative processes and provide a platform to investigate how CRLs regulate stem cells in vivo.}, } @article {pmid29291973, year = {2018}, author = {Seifert, AW and Muneoka, K}, title = {The blastema and epimorphic regeneration in mammals.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {190-199}, pmid = {29291973}, issn = {1095-564X}, support = {R01 AR070313/AR/NIAMS NIH HHS/United States ; }, mesh = {Amputation ; Animals ; Antlers/physiology ; Deer/physiology ; Ear Auricle/injuries/physiology ; Finger Injuries/physiopathology ; Fingers/physiology ; Humans ; Mammals/*physiology ; Mice ; Morphogenesis ; Murinae/physiology ; Regeneration/*physiology ; Stem Cells/physiology ; Toes/physiology ; Wound Healing/physiology ; }, abstract = {Studying regeneration in animals where and when it occurs is inherently interesting and a challenging research topic within developmental biology. Historically, vertebrate regeneration has been investigated in animals that display enhanced regenerative abilities and we have learned much from studying organ regeneration in amphibians and fish. From an applied perspective, while regeneration biologists will undoubtedly continue to study poikilothermic animals (i.e., amphibians and fish), studies focused on homeotherms (i.e., mammals and birds) are also necessary to advance regeneration biology. Emerging mammalian models of epimorphic regeneration are poised to help link regenerative biology and regenerative medicine. The regenerating rodent digit tip, which parallels human fingertip regeneration, and the regeneration of large circular defects through the ear pinna in spiny mice and rabbits, provide tractable, experimental systems where complex tissue structures are regrown through blastema formation and morphogenesis. Using these models as examples, we detail similarities and differences between the mammalian blastema and its classical counterpart to arrive at a broad working definition of a vertebrate regeneration blastema. This comparison leads us to conclude that regenerative failure is not related to the availability of regeneration-competent progenitor cells, but is most likely a function of the cellular response to the microenvironment that forms following traumatic injury. Recent studies demonstrating that targeted modification of this microenvironment can restrict or enhance regenerative capabilities in mammals helps provide a roadmap for eventually pushing the limits of human regeneration.}, } @article {pmid29291972, year = {2018}, author = {McLaughlin, KA and Levin, M}, title = {Bioelectric signaling in regeneration: Mechanisms of ionic controls of growth and form.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {177-189}, pmid = {29291972}, issn = {1095-564X}, support = {R01 AR055993/AR/NIAMS NIH HHS/United States ; R01 AR061988/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/physiology ; *Biophysical Phenomena ; Body Patterning/physiology ; Cell Division ; Cell Movement ; *Electromagnetic Phenomena ; Gap Junctions/physiology ; Humans ; Intracellular Signaling Peptides and Proteins/physiology ; Ion Channels/physiology ; Ions/*metabolism ; Membrane Potentials ; Organ Size ; Plant Physiological Phenomena ; Regeneration/*physiology ; Second Messenger Systems ; }, abstract = {The ability to control pattern formation is critical for the both the embryonic development of complex structures as well as for the regeneration/repair of damaged or missing tissues and organs. In addition to chemical gradients and gene regulatory networks, endogenous ion flows are key regulators of cell behavior. Not only do bioelectric cues provide information needed for the initial development of structures, they also enable the robust restoration of normal pattern after injury. In order to expand our basic understanding of morphogenetic processes responsible for the repair of complex anatomy, we need to identify the roles of endogenous voltage gradients, ion flows, and electric fields. In complement to the current focus on molecular genetics, decoding the information transduced by bioelectric cues enhances our knowledge of the dynamic control of growth and pattern formation. Recent advances in science and technology place us in an exciting time to elucidate the interplay between molecular-genetic inputs and important biophysical cues that direct the creation of tissues and organs. Moving forward, these new insights enable additional approaches to direct cell behavior and may result in profound advances in augmentation of regenerative capacity.}, } @article {pmid29291971, year = {2018}, author = {Lee, JH and Rawlins, EL}, title = {Developmental mechanisms and adult stem cells for therapeutic lung regeneration.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {166-176}, doi = {10.1016/j.ydbio.2017.09.016}, pmid = {29291971}, issn = {1095-564X}, support = {107633/Z/15/Z//Wellcome Trust/United Kingdom ; C6946/A14492//Cancer Research UK/United Kingdom ; 092096//Wellcome Trust/United Kingdom ; 07922/Z/11/Z//Wellcome Trust/United Kingdom ; MR/P009581/1//Medical Research Council/United Kingdom ; MC_PC_12009//Medical Research Council/United Kingdom ; }, mesh = {Adult ; Adult Stem Cells/*transplantation ; Alveolar Epithelial Cells/physiology ; Animals ; Disease Models, Animal ; Fibroblasts/physiology ; Humans ; Lung/blood supply/cytology/embryology/*physiology ; Lung Diseases/*therapy ; Macrophages/physiology ; Mesoderm/physiology ; Mice ; Organogenesis ; Organoids/transplantation ; Pneumonectomy ; Regeneration/*physiology ; Respiratory System/cytology ; }, abstract = {Chronic degenerative lung diseases are essentially untreatable pathological conditions. By contrast, the healthy lung has numerous mechanisms that allow for rapid repair and restoration of function following minor acute injuries. We discuss the normal endogenous processes of lung development, homeostatic maintenance and repair and consider the research strategies required for the development of methods for human therapeutic lung regeneration.}, } @article {pmid29291970, year = {2018}, author = {Llonch, S and Carido, M and Ader, M}, title = {Organoid technology for retinal repair.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {132-143}, doi = {10.1016/j.ydbio.2017.09.028}, pmid = {29291970}, issn = {1095-564X}, mesh = {Animals ; Cellular Reprogramming Techniques ; Culture Media, Serum-Free/pharmacology ; Embryonic Stem Cells/cytology/drug effects ; Humans ; Induced Pluripotent Stem Cells/transplantation ; Mice ; Morphogenesis ; Organoids/*transplantation ; Photoreceptor Cells, Vertebrate/transplantation ; Pluripotent Stem Cells/*transplantation ; Retina/cytology ; Retinal Degeneration/*therapy ; Species Specificity ; *Tissue Culture Techniques ; Translational Medical Research ; }, abstract = {A major cause for vision impairment and blindness in industrialized countries is the loss of the light-sensing retinal tissue in the eye. Photoreceptor damage is one of the main characteristics found in retinal degeneration diseases, such as Retinitis Pigmentosa or age-related macular degeneration. The lack of effective therapies to stop photoreceptor loss together with the absence of significant intrinsic regeneration in the human retina converts such degenerative diseases into permanent conditions that are currently irreversible. Cell replacement by means of photoreceptor transplantation has been proposed as a potential approach to tackle cell loss in the retina. Since the first attempt of photoreceptor transplantation in humans, about twenty years ago, several research groups have focused in the development and improvement of technologies necessary to bring cell transplantation for retinal degeneration diseases to reality. Progress in recent years in the generation of human tissue derived from pluripotent stem cells (PSCs) has significantly improved our tools to study human development and disease in the dish. Particularly the availability of 3D culture systems for the generation of PSC-derived organoids, including the human retina, has dramatically increased access to human material for basic and medical research. In this review, we focus on important milestones towards the generation of transplantable photoreceptor precursors from PSC-derived retinal organoids and discuss recent pre-clinical transplantation studies using organoid-derived photoreceptors in context to related in vivo work using primary photoreceptors as donor material. Additionally, we summarize remaining challenges for developing photoreceptor transplantation towards clinical application.}, } @article {pmid29291969, year = {2018}, author = {Echeverri, K and Zayas, RM}, title = {Regeneration: From cells to tissues to organisms.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {109-110}, pmid = {29291969}, issn = {1095-564X}, support = {R01 HD092451/HD/NICHD NIH HHS/United States ; }, } @article {pmid29291903, year = {2018}, author = {}, title = {How Do You Incorporate 21st Century Genetics into Your Undergraduate Course?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {79-82}, doi = {10.1016/j.tig.2017.12.002}, pmid = {29291903}, issn = {0168-9525}, mesh = {Education, Medical, Undergraduate/*methods ; Faculty/*education ; Genetic Engineering/ethics/methods ; Genetics, Medical/*education/instrumentation/methods ; Humans ; Problem-Based Learning/trends ; }, } @article {pmid29291902, year = {2018}, author = {}, title = {What Are Some of the Major Challenges in Teaching/Designing Genetics Courses Today?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {82-85}, doi = {10.1016/j.tig.2017.12.003}, pmid = {29291902}, issn = {0168-9525}, mesh = {Education, Medical, Undergraduate/*methods ; Faculty/*education ; Genetics, Medical/*education/instrumentation/methods ; Humans ; Knowledge of Results (Psychology) ; Problem-Based Learning/trends ; }, } @article {pmid29291750, year = {2018}, author = {Vernon, I and Liu, J and Goldstein, M and Rowe, J and Topping, J and Lindsey, K}, title = {Bayesian uncertainty analysis for complex systems biology models: emulation, global parameter searches and evaluation of gene functions.}, journal = {BMC systems biology}, volume = {12}, number = {1}, pages = {1}, pmid = {29291750}, issn = {1752-0509}, support = {BB/E006531/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {BACKGROUND: Many mathematical models have now been employed across every area of systems biology. These models increasingly involve large numbers of unknown parameters, have complex structure which can result in substantial evaluation time relative to the needs of the analysis, and need to be compared to observed data of various forms. The correct analysis of such models usually requires a global parameter search, over a high dimensional parameter space, that incorporates and respects the most important sources of uncertainty. This can be an extremely difficult task, but it is essential for any meaningful inference or prediction to be made about any biological system. It hence represents a fundamental challenge for the whole of systems biology.

METHODS: Bayesian statistical methodology for the uncertainty analysis of complex models is introduced, which is designed to address the high dimensional global parameter search problem. Bayesian emulators that mimic the systems biology model but which are extremely fast to evaluate are embeded within an iterative history match: an efficient method to search high dimensional spaces within a more formal statistical setting, while incorporating major sources of uncertainty.

RESULTS: The approach is demonstrated via application to a model of hormonal crosstalk in Arabidopsis root development, which has 32 rate parameters, for which we identify the sets of rate parameter values that lead to acceptable matches between model output and observed trend data. The multiple insights into the model's structure that this analysis provides are discussed. The methodology is applied to a second related model, and the biological consequences of the resulting comparison, including the evaluation of gene functions, are described.

CONCLUSIONS: Bayesian uncertainty analysis for complex models using both emulators and history matching is shown to be a powerful technique that can greatly aid the study of a large class of systems biology models. It both provides insight into model behaviour and identifies the sets of rate parameters of interest.}, } @article {pmid29291749, year = {2018}, author = {Shokoohizadeh, L and Ekrami, A and Labibzadeh, M and Ali, L and Alavi, SM}, title = {Antimicrobial resistance patterns and virulence factors of enterococci isolates in hospitalized burn patients.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {1}, pmid = {29291749}, issn = {1756-0500}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/genetics ; *Burn Units ; Burns/*microbiology ; Carbon-Oxygen Ligases/genetics ; Drug Resistance, Bacterial/*genetics ; *Enterococcus faecalis/genetics/isolation & purification/pathogenicity ; *Enterococcus faecium/genetics/isolation & purification/pathogenicity ; Humans ; Iran ; Microbial Sensitivity Tests ; Polymerase Chain Reaction ; Vancomycin/pharmacology ; Vancomycin Resistance/*genetics ; *Virulence Factors/genetics/isolation & purification ; }, abstract = {OBJECTIVE: The objective of this study was to determine the frequency of the antimicrobial resistance and genes encoding virulence factors of enterococci isolated in hospitalized burn patients in a major burn center in Ahvaz, southwest of Iran. A total of 340 bacterial isolates were collected from the burn center from February 2014 to February 2015. The antimicrobial susceptibility and MIC of vancomycin were determined using the disk diffusion and micro-agar dilution techniques. The genus and species-specific genes, potential virulence genes, and vanA and vanB genes were detected by polymerase chain reaction.

RESULTS: According to our results, out of the 340 bacterial isolates, 16.4% (n = 56) were identified as enterococci. Out of the 56 enterococcal isolates, 35 (62.5%) were Enterococcus faecalis and 21 (37.5%) were Enterococcus faecium. More than 20% (n = 5) of E. faecium demonstrated resistance to vancomycin. The gelE and asa genes were the most prevalent virulence genes in E. faecalis (48.5%) and E. faecium (43%) isolates. The emergence of vancomycin resistant E. faecium strains which have several virulence factors should be considered as a major cause of concern for burn centers. Control and management of infections induced by enterococci should be regarded as highly important in burn patients.}, } @article {pmid29291746, year = {2018}, author = {Kumaresan, D and Stephenson, J and Doxey, AC and Bandukwala, H and Brooks, E and Hillebrand-Voiculescu, A and Whiteley, AS and Murrell, JC}, title = {Aerobic proteobacterial methylotrophs in Movile Cave: genomic and metagenomic analyses.}, journal = {Microbiome}, volume = {6}, number = {1}, pages = {1}, pmid = {29291746}, issn = {2049-2618}, support = {NE/G017956//Natural Environment Research Council/International ; }, mesh = {Aerobiosis ; Genomics/*methods ; Geologic Sediments/microbiology ; Metagenomics ; Methane/*chemistry ; Phylogeny ; Proteobacteria/*classification/genetics/*isolation & purification ; Romania ; Sequence Analysis, DNA ; }, abstract = {BACKGROUND: Movile Cave (Mangalia, Romania) is a unique ecosystem where the food web is sustained by microbial primary production, analogous to deep-sea hydrothermal vents. Specifically, chemoautotrophic microbes deriving energy from the oxidation of hydrogen sulphide and methane form the basis of the food web.

RESULTS: Here, we report the isolation of the first methane-oxidizing bacterium from the Movile Cave ecosystem, Candidatus Methylomonas sp. LWB, a new species and representative of Movile Cave microbial mat samples. While previous research has suggested a prevalence of anoxic conditions in deeper lake water and sediment, using small-scale shotgun metagenome sequencing, we show that metabolic genes encoding enzymes for aerobic methylotrophy are prevalent in sediment metagenomes possibly indicating the presence of microoxic conditions. Moreover, this study also indicates that members within the family Gallionellaceae (Sideroxydans and Gallionella) were the dominant taxa within the sediment microbial community, thus suggesting a major role for microaerophilic iron-oxidising bacteria in nutrient cycling within the Movile Cave sediments.

CONCLUSIONS: In this study, based on phylogenetic and metabolic gene surveys of metagenome sequences, the possibility of aerobic microbial processes (i.e., methylotrophy and iron oxidation) within the sediment is indicated. We also highlight significant gaps in our knowledge on biogeochemical cycles within the Movile Cave ecosystem, and the need to further investigate potential feedback mechanisms between microbial communities in both lake sediment and lake water.}, } @article {pmid29291742, year = {2018}, author = {Scharnagl, K and Sanchez, V and von Wettberg, E}, title = {The impact of salinity on mycorrhizal colonization of a rare legume, Galactia smallii, in South Florida pine rocklands.}, journal = {BMC research notes}, volume = {11}, number = {1}, pages = {2}, pmid = {29291742}, issn = {1756-0500}, support = {2011-38420-20053//USDA NIFA NNF/ ; }, mesh = {Biomass ; *Fabaceae/anatomy & histology/metabolism/microbiology ; Florida ; Mycorrhizae/*physiology ; *Plant Roots/anatomy & histology/metabolism/microbiology ; *Salinity ; *Soil/chemistry ; *Soil Microbiology ; Symbiosis/*physiology ; }, abstract = {OBJECTIVES: The success of restoration plantings depends on the capacity of transplanted individuals or seeds to establish and reproduce. It is increasingly recognized that restoration success depends quite heavily upon biotic interactions and belowground processes. Under stressful abiotic conditions, such as soils salinized by storm surge and sea level rise, symbiotic interactions with soil microbes such as mycorrhizae may be critically important. In this study, we investigate the impact of salinity on percent colonization of roots by arbuscular mycorrhizal fungi, in addition to the impacts of this colonization on plant fitness under saline conditions. Fifty Galactia smallii plants from an ex situ collection were subjected to a salinity treatment for 6 weeks, and 50 plants were untreated. Plants were harvested and assessed for percent colonization by arbuscular mycorrhizal fungi, nodule number, shoot and root dry biomass, and micronutrient content.

RESULTS: Colonization by arbuscular mycorrhizae was higher in plants in the salinity treatment than in untreated plants; plants in the salinity treatment were also found to have a lower root:shoot ratio, and higher phosphorus and nitrogen levels. These results support the importance of arbuscular mycorrhizal fungi in restoration efforts of endangered plants in fragmented and threatened ecosystems, such as pine rocklands.}, } @article {pmid29291734, year = {2018}, author = {Alam, Z and Roncal, J and Peña-Castillo, L}, title = {Genetic variation associated with healthy traits and environmental conditions in Vaccinium vitis-idaea.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {4}, pmid = {29291734}, issn = {1471-2164}, support = {5404.1722.101//Research and Development Corporation of Newfoundland and Labrador/International ; }, mesh = {Antioxidants/analysis ; Environment ; Gene Library ; Phenols/analysis ; Phenotype ; Phylogeny ; Plant Proteins/genetics ; *Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; Vaccinium vitis-idaea/chemistry/*genetics ; }, abstract = {BACKGROUND: Lingonberry (Vaccinium vitis-idaea L.), one of the least studied fruit crops in the Ericaceae family, has a dramatically increased worldwide demand due to its numerous health benefits. Genetic markers can facilitate the selection of berries with desirable climatic adaptations, agronomic and nutritious characteristics to improve cultivation programs. However, no genomic resources are available for this species.

RESULTS: We used Genotyping-by-Sequencing (GBS) to analyze the genetic variation of 56 lingonberry samples from across Newfoundland and Labrador, Canada. To elucidate a potential adaptation to environmental conditions we searched for genotype-environment associations by applying three distinct approaches to screen the identified single nucleotide polymorphisms (SNPs) for correlation with six environmental variables. We also searched for an association between the identified SNPs and two phenotypic traits: the total phenolic content (TPC) and antioxidant capacity (AC) of fruit. We identified 1586 high-quality putative SNPs using the UNEAK pipeline available in TASSEL. We found 132 SNPs likely associated with at least one of the environmental or phenotypic variables. To obtain insights on the function of the genomic sequences containing the SNPs likely to be associated with the environmental or phenotypic variables, we performed a sequence-based functional annotation and identified homologous protein-coding sequences with functional roles related to abiotic stress response, pathogen defense, RNA metabolism, and, most interestingly, phenolic compound biosynthesis.

CONCLUSIONS: The putative SNPs discovered are the first genomic resource for lingonberry. This resource might prove useful in high-density quantitative trait locus analysis, and association mapping. The identified candidate genes containing the SNPs need further studies on their potential role in local adaptation of lingonberry. Altogether, the present study provides new resources that can be used to breed for desirable traits in lingonberry.}, } @article {pmid29291729, year = {2018}, author = {Behr, M and Sergeant, K and Leclercq, CC and Planchon, S and Guignard, C and Lenouvel, A and Renaut, J and Hausman, JF and Lutts, S and Guerriero, G}, title = {Insights into the molecular regulation of monolignol-derived product biosynthesis in the growing hemp hypocotyl.}, journal = {BMC plant biology}, volume = {18}, number = {1}, pages = {1}, pmid = {29291729}, issn = {1471-2229}, support = {C13/SR/5774202//Fonds National de la Recherche Luxembourg/International ; }, mesh = {Cannabis/genetics/*metabolism ; *Gene Expression ; Hypocotyl/*metabolism ; Laccase/genetics/metabolism ; Lignans/*biosynthesis ; Lignin/*biosynthesis ; Peroxidase/genetics/metabolism ; Proteomics ; }, abstract = {BACKGROUND: Lignin and lignans are both derived from the monolignol pathway. Despite the similarity of their building blocks, they fulfil different functions in planta. Lignin strengthens the tissues of the plant, while lignans are involved in plant defence and growth regulation. Their biosyntheses are tuned both spatially and temporally to suit the development of the plant (water conduction, reaction to stresses). We propose to study the general molecular events related to monolignol-derived product biosynthesis, especially lignin. It was previously shown that the growing hemp hypocotyl (between 6 and 20 days after sowing) is a valid system to study secondary growth and the molecular events accompanying lignification. The present work confirms the validity of this system, by using it to study the regulation of lignin and lignan biosynthesis. Microscopic observations, lignin analysis, proteomics, together with in situ laccase and peroxidase activity assays were carried out to understand the dynamics of lignin synthesis during the development of the hemp hypocotyl.

RESULTS: Based on phylogenetic analysis and targeted gene expression, we suggest a role for the hemp dirigent and dirigent-like proteins in lignan biosynthesis. The transdisciplinary approach adopted resulted in the gene- and protein-level quantification of the main enzymes involved in the biosynthesis of monolignols and their oxidative coupling (laccases and class III peroxidases), in lignin deposition (dirigent-like proteins) and in the determination of the stereoconformation of lignans (dirigent proteins).

CONCLUSIONS: Our work sheds light on how, in the growing hemp hypocotyl, the provision of the precursors needed to synthesize the aromatic biomolecules lignin and lignans is regulated at the transcriptional and proteomic level.}, } @article {pmid29291727, year = {2018}, author = {Lasserre, M and Fresia, P and Greif, G and Iraola, G and Castro-Ramos, M and Juambeltz, A and Nuñez, Á and Naya, H and Robello, C and Berná, L}, title = {Whole genome sequencing of the monomorphic pathogen Mycobacterium bovis reveals local differentiation of cattle clinical isolates.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {2}, pmid = {29291727}, issn = {1471-2164}, support = {POS_NAC_2015_1_109466//Agencia Nacional de Investigación e Innovación (UY)/International ; 328//Fondo de Promoción de Tecnología Agropecuaria (FPTA)/International ; DCI-ALA/2011/023-502//Agencia Nacional de Investigación e Innovación/International ; COF 03/11//FOCEM (MERCOSUR Structural Convergence Fund)/International ; Fondo Caldeyro Barcia//Agencia Nacional de Investigación e Innovación (UY)/International ; }, mesh = {Animals ; Cattle/*microbiology ; *Genome, Bacterial ; Genomics ; Genotype ; Mycobacterium bovis/classification/*genetics/isolation & purification ; Phylogeny ; Uruguay ; }, abstract = {BACKGROUND: Bovine tuberculosis (bTB) poses serious risks to animal welfare and economy, as well as to public health as a zoonosis. Its etiological agent, Mycobacterium bovis, belongs to the Mycobacterium tuberculosis complex (MTBC), a group of genetically monomorphic organisms featured by a remarkably high overall nucleotide identity (99.9%). Indeed, this characteristic is of major concern for correct typing and determination of strain-specific traits based on sequence diversity. Due to its historical economic dependence on cattle production, Uruguay is deeply affected by the prevailing incidence of Mycobacterium bovis. With the world's highest number of cattle per human, and its intensive cattle production, Uruguay represents a particularly suited setting to evaluate genomic variability among isolates, and the diversity traits associated to this pathogen.

RESULTS: We compared 186 genomes from MTBC strains isolated worldwide, and found a highly structured population in M. bovis. The analysis of 23 new M. bovis genomes, belonging to strains isolated in Uruguay evidenced three groups present in the country. Despite presenting an expected highly conserved genomic structure and sequence, these strains segregate into a clustered manner within the worldwide phylogeny. Analysis of the non-pe/ppe differential areas against a reference genome defined four main sources of variability, namely: regions of difference (RD), variable genes, duplications and novel genes. RDs and variant analysis segregated the strains into clusters that are concordant with their spoligotype identities. Due to its high homoplasy rate, spoligotyping failed to reflect the true genomic diversity among worldwide representative strains, however, it remains a good indicator for closely related populations.

CONCLUSIONS: This study introduces a comprehensive population structure analysis of worldwide M. bovis isolates. The incorporation and analysis of 23 novel Uruguayan M. bovis genomes, sheds light onto the genomic diversity of this pathogen, evidencing the existence of greater genetic variability among strains than previously contemplated.}, } @article {pmid29291722, year = {2018}, author = {Marco-Ramell, A and Palau-Rodriguez, M and Alay, A and Tulipani, S and Urpi-Sarda, M and Sanchez-Pla, A and Andres-Lacueva, C}, title = {Evaluation and comparison of bioinformatic tools for the enrichment analysis of metabolomics data.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {1}, pmid = {29291722}, issn = {1471-2105}, support = {PI13/01172//ISCII-Subdirección General de Evaluación y Fomento de la Investigación/International ; 2014SGR1566//Generalitat de Catalunya's Agency AGAUR/International ; 2014 SGR 464//Generalitat de Catalunya's Agency AGAUR/International ; Juan de la Cierva postdoctoral fellowship//MINECO/International ; Juan de la Cierva postdoctoral fellowship//MINECO/International ; Ramon y Cajal postdoctoral fellowship//MINECO/International ; MTM2015-64465-C2-1-R//MINECO/International ; APIF predoctoral fellowship//Universitat de Barcelona/International ; }, mesh = {Computational Biology/*methods ; *Databases, Factual ; Humans ; *Metabolome ; Metabolomics/*methods ; }, abstract = {BACKGROUND: Bioinformatic tools for the enrichment of 'omics' datasets facilitate interpretation and understanding of data. To date few are suitable for metabolomics datasets. The main objective of this work is to give a critical overview, for the first time, of the performance of these tools. To that aim, datasets from metabolomic repositories were selected and enriched data were created. Both types of data were analysed with these tools and outputs were thoroughly examined.

RESULTS: An exploratory multivariate analysis of the most used tools for the enrichment of metabolite sets, based on a non-metric multidimensional scaling (NMDS) of Jaccard's distances, was performed and mirrored their diversity. Codes (identifiers) of the metabolites of the datasets were searched in different metabolite databases (HMDB, KEGG, PubChem, ChEBI, BioCyc/HumanCyc, LipidMAPS, ChemSpider, METLIN and Recon2). The databases that presented more identifiers of the metabolites of the dataset were PubChem, followed by METLIN and ChEBI. However, these databases had duplicated entries and might present false positives. The performance of over-representation analysis (ORA) tools, including BioCyc/HumanCyc, ConsensusPathDB, IMPaLA, MBRole, MetaboAnalyst, Metabox, MetExplore, MPEA, PathVisio and Reactome and the mapping tool KEGGREST, was examined. Results were mostly consistent among tools and between real and enriched data despite the variability of the tools. Nevertheless, a few controversial results such as differences in the total number of metabolites were also found. Disease-based enrichment analyses were also assessed, but they were not found to be accurate probably due to the fact that metabolite disease sets are not up-to-date and the difficulty of predicting diseases from a list of metabolites.

CONCLUSIONS: We have extensively reviewed the state-of-the-art of the available range of tools for metabolomic datasets, the completeness of metabolite databases, the performance of ORA methods and disease-based analyses. Despite the variability of the tools, they provided consistent results independent of their analytic approach. However, more work on the completeness of metabolite and pathway databases is required, which strongly affects the accuracy of enrichment analyses. Improvements will be translated into more accurate and global insights of the metabolome.}, } @article {pmid29291715, year = {2018}, author = {Groß, U and Brzuszkiewicz, E and Gunka, K and Starke, J and Riedel, T and Bunk, B and Spröer, C and Wetzel, D and Poehlein, A and Chibani, C and Bohne, W and Overmann, J and Zimmermann, O and Daniel, R and Liesegang, H}, title = {Comparative genome and phenotypic analysis of three Clostridioides difficile strains isolated from a single patient provide insight into multiple infection of C. difficile.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {1}, pmid = {29291715}, issn = {1471-2164}, support = {VWZN2889/3215//Niedersächsisches Vorab/International ; }, mesh = {Clostridiales/classification/cytology/*genetics/isolation & purification ; Flagella/genetics/ultrastructure ; Gene Transfer, Horizontal ; *Genome, Bacterial ; Genomics ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Phenotype ; Phylogeny ; }, } @article {pmid29291710, year = {2018}, author = {Shi, M and Umbach, DM and Wise, AS and Weinberg, CR}, title = {Simulating autosomal genotypes with realistic linkage disequilibrium and a spiked-in genetic effect.}, journal = {BMC bioinformatics}, volume = {19}, number = {1}, pages = {2}, pmid = {29291710}, issn = {1471-2105}, support = {Z01 ES040007/ES/NIEHS NIH HHS/United States ; }, mesh = {Algorithms ; Alleles ; Case-Control Studies ; *Computer Simulation ; Gene Frequency ; Genetic Association Studies ; Genome-Wide Association Study/*methods ; *Genotype ; Humans ; *Linkage Disequilibrium ; *Models, Genetic ; Phenotype ; *Polymorphism, Single Nucleotide ; }, abstract = {BACKGROUND: To evaluate statistical methods for genome-wide genetic analyses, one needs to be able to simulate realistic genotypes. We here describe a method, applicable to a broad range of association study designs, that can simulate autosome-wide single-nucleotide polymorphism data with realistic linkage disequilibrium and with spiked in, user-specified, single or multi-SNP causal effects.

RESULTS: Our construction uses existing genome-wide association data from unrelated case-parent triads, augmented by including a hypothetical complement triad for each triad (same parents but with a hypothetical offspring who carries the non-transmitted parental alleles). We assign offspring qualitative or quantitative traits probabilistically through a specified risk model and show that our approach destroys the risk signals from the original data. Our method can simulate genetically homogeneous or stratified populations and can simulate case-parents studies, case-control studies, case-only studies, or studies of quantitative traits. We show that allele frequencies and linkage disequilibrium structure in the original genome-wide association sample are preserved in the simulated data. We have implemented our method in an R package (TriadSim) which is freely available at the comprehensive R archive network.

CONCLUSION: We have proposed a method for simulating genome-wide SNP data with realistic linkage disequilibrium. Our method will be useful for developing statistical methods for studying genetic associations, including higher order effects like epistasis and gene by environment interactions.}, } @article {pmid29291709, year = {2018}, author = {Zhao, L and Ning, S and Yi, Y and Zhang, L and Yuan, Z and Wang, J and Zheng, Y and Hao, M and Liu, D}, title = {Fluorescence in situ hybridization karyotyping reveals the presence of two distinct genomes in the taxon Aegilops tauschii.}, journal = {BMC genomics}, volume = {19}, number = {1}, pages = {3}, pmid = {29291709}, issn = {1471-2164}, mesh = {*Genome, Plant ; In Situ Hybridization, Fluorescence ; Karyotyping ; Oligonucleotide Probes ; Poaceae/anatomy & histology/classification/*genetics ; }, abstract = {BACKGROUND: Aegilops tauschii is the donor of the bread wheat D genome. Based on spike morphology, the taxon has conventionally been subdivided into ssp. tauschii and ssp. strangulata. The present study was intended to address the poor match between this whole plant morphology-based subdivision and genetic relationships inferred from genotyping by fluorescence in situ hybridization karyotyping a set of 31 Ae. tauschii accessions.

RESULTS: The distribution of sites hybridizing to the two probes oligo-pTa-535 and (CTT)10 split the Ae. tauschii accessions into two clades, designated Dt and Ds, which corresponded perfectly with a previously assembled phylogeny based on marker genotype. The Dt cluster was populated exclusively by ssp. tauschii accessions, while the Ds cluster harbored both ssp. strangulata and morphologically intermediate accessions. As a result, it is proposed that Ae. tauschii ssp. tauschii is restricted to carriers of the Dt karyotype: their spikelets are regularly spaced along the rachis, at least in the central portion of their spike. Accessions classified as Ae. tauschii ssp. strangulata carry the Ds karyotype; their spikelets are irregularly spaced. Based on this criterion, forms formerly classified as ssp. tauschii var. meyeri have been re-designated ssp. strangulata var. meyeri.

CONCLUSIONS: According to the reworking of the taxon, the bread wheat D genome was most probably donated by ssp. strangulata var. meyeri. Chromosomal differentiation reveals intra-species taxon of Ae. tauschii. Ae. tauschii ssp. tauschii has more distant relationship with breed wheat than ssp. strangulata and can be used for breeding improving effectively.}, } @article {pmid29291597, year = {2018}, author = {Martín-Navarro, I and Brodie, JP and Romanowsky, AJ and Ruiz-Lara, T and van de Ven, G}, title = {Black-hole-regulated star formation in massive galaxies.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {307-309}, doi = {10.1038/nature24999}, pmid = {29291597}, issn = {1476-4687}, abstract = {Supermassive black holes, with masses more than a million times that of the Sun, seem to inhabit the centres of all massive galaxies. Cosmologically motivated theories of galaxy formation require feedback from these supermassive black holes to regulate star formation. In the absence of such feedback, state-of-the-art numerical simulations fail to reproduce the number density and properties of massive galaxies in the local Universe. There is, however, no observational evidence of this strongly coupled coevolution between supermassive black holes and star formation, impeding our understanding of baryonic processes within galaxies. Here we report that the star formation histories of nearby massive galaxies, as measured from their integrated optical spectra, depend on the mass of the central supermassive black hole. Our results indicate that the black-hole mass scales with the gas cooling rate in the early Universe. The subsequent quenching of star formation takes place earlier and more efficiently in galaxies that host higher-mass central black holes. The observed relation between black-hole mass and star formation efficiency applies to all generations of stars formed throughout the life of a galaxy, revealing a continuous interplay between black-hole activity and baryon cooling.}, } @article {pmid29291450, year = {2018}, author = {Medeiros, JM and Böck, D and Pilhofer, M}, title = {Imaging bacteria inside their host by cryo-focused ion beam milling and electron cryotomography.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {62-68}, doi = {10.1016/j.mib.2017.12.006}, pmid = {29291450}, issn = {1879-0364}, mesh = {Bacteria/*ultrastructure ; Cryoelectron Microscopy/instrumentation/*methods ; Electron Microscope Tomography/instrumentation/methods ; *Host Microbial Interactions ; Macromolecular Substances/ultrastructure ; Molecular Imaging/instrumentation/*methods ; }, abstract = {Bacterium-host interactions are important for diverse ecological settings including pathogenicity and symbiosis. Electron cryotomography is a powerful method for studying the macromolecular complexes that mediate such interactions in situ. The main limitation of electron cryotomography is its restriction to relatively thin samples such as individual bacterial cells. Cryo-focused ion beam milling was recently proposed as a solution to the thickness limitation. This approach allows the artifact-free thinning of biological specimens for subsequent imaging in the transmission electron microscope. By enabling near-native imaging of bacteria inside their eukaryotic host, this combination of techniques promotes the integration of data from structural biology and infection biology. Therefore, electron cryotomography associated with cryo-focused ion beam milling holds great potential for establishing multiscale models of cell-cell interactions from the atomic, to the cellular and to the intercellular scale.}, } @article {pmid29290403, year = {2018}, author = {Gao, J and Colaiácovo, MP}, title = {Zipping and Unzipping: Protein Modifications Regulating Synaptonemal Complex Dynamics.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {232-245}, pmid = {29290403}, issn = {0168-9525}, support = {R01 GM072551/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Chromosome Segregation/*genetics ; Crossing Over, Genetic/*genetics ; *DNA Breaks, Double-Stranded ; Humans ; Models, Genetic ; *Protein Processing, Post-Translational ; Saccharomyces cerevisiae/genetics/metabolism ; Synaptonemal Complex/*genetics/metabolism ; }, abstract = {The proteinaceous zipper-like structure known as the synaptonemal complex (SC), which forms between pairs of homologous chromosomes during meiosis from yeast to humans, plays important roles in promoting interhomolog crossover formation, regulating cessation of DNA double-strand break (DSB) formation following crossover designation, and ensuring accurate meiotic chromosome segregation. Recent studies are starting to reveal critical roles for different protein modifications in regulating SC dynamics. Protein SUMOylation, N-terminal acetylation, and phosphorylation have been shown to be essential for the regulated assembly and disassembly of the SC. Moreover, phosphorylation of specific SC components has been found to link changes in SC dynamics with meiotic recombination. This review highlights the latest findings on how protein modifications regulate SC dynamics and functions.}, } @article {pmid29290402, year = {2018}, author = {Ballinger, MA and Noor, MAF}, title = {Are Lethal Alleles Too Abundant in Humans?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {87-89}, doi = {10.1016/j.tig.2017.12.013}, pmid = {29290402}, issn = {0168-9525}, support = {S10 OD018164/OD/NIH HHS/United States ; }, mesh = {Alleles ; *Genes, Lethal ; Genes, Recessive ; Humans ; *Mutation ; }, abstract = {Across species, many individuals carry one or more recessive lethal alleles, posing an evolutionary conundrum for their persistence. Using a population genomic approach, Amorim et al. studied the abundance of lethal disease-causing mutations in humans and found that, while appearing more common than expected, most may nonetheless persist at frequencies predicted by mutation-selection balance.}, } @article {pmid29289979, year = {2018}, author = {Pietryczuk, A and Cudowski, A and Hauschild, T and Świsłocka, M and Więcko, A and Karpowicz, M}, title = {Abundance and Species Diversity of Fungi in Rivers with Various Contaminations.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {630-638}, pmid = {29289979}, issn = {1432-0991}, mesh = {*Biodiversity ; Fungi/classification/genetics/*isolation & purification/metabolism ; Phylogeny ; Rivers/*microbiology ; Water Pollutants, Chemical/*analysis/metabolism ; }, abstract = {The main objective of this work was to determine the abundance and species diversity of fungi in the waters of selected rivers of Central Europe, NE Poland (Augustów Lakeland), differing in size, physical and chemical properties, and streamflow rate. The minimum abundance of fungi in the analysed rivers was recorded for a river with low concentration of organic matter (8200 CFU/mL, Czarna Hańcza River), and maximum for a strongly anthropogenically polluted river (24,800 CFU/mL, Kamienny Bród River). A total of 49 fungal species were identified based on PCR ITS-RFLP and DNA sequencing methods. However, RFLP-PCR method has proved to be sufficient to determine the species of 34 fungi. The highest taxonomic diversity was determined for the waters abundant in organic matter (Piecówka and Rospuda Rivers), and the lowest for rivers poor in organic matter (Netta and Czarna Hańcza Rivers). From the 49 identified species, 47% were aquatic hyphomycetes, and 18% were potentially pathogenic fungi mainly occurring in the waters of polluted rivers with increased organic matter concentrations. Moreover, a higher number of fungal taxa were recorded in fluvial waters distinguished by higher streamflow rate, and therefore, stronger water turbulence. The study results suggest that the most important factors influencing the structure of mycoplankton in rivers include pH of water, content of organic matter, degree of anthropogenic pollution, and streamflow rate.}, } @article {pmid29289978, year = {2018}, author = {Siddiqi, MZ and Lee, SY and Choi, KD and Im, WT}, title = {Aeromicrobium panacisoli sp. nov. Isolated from Soil of Ginseng Cultivating Field.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {624-629}, pmid = {29289978}, issn = {1432-0991}, support = {2014M3A6A8066437//and by the Intelligent Synthetic Biology Center of Global Frontier Project funded by the Ministry of Education, Science and Technology/ ; }, mesh = {Actinomycetales/classification/genetics/*isolation & purification/metabolism ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry/metabolism ; Panax/*growth & development ; Phylogeny ; Republic of Korea ; *Soil Microbiology ; }, abstract = {A Gram-positive, rod-shaped, non-spore-forming, and aerobic bacterium (Gsoil 137T) was isolated from soil of a ginseng field of Pocheon province in South Korea and subjected to a polyphasic approach in order to determine its taxonomic position. On the basis of 16S rRNA gene sequence similarity, strain Gsoil 137T was shown to belong to the family Nocardioidaceae and was closely related to Aeromicrobium ginsengisoli Gsoil 098T (96.7%), Aeromicrobium panaciterrae (96.7%), and Aeromicrobium halocynthiae JCM 15749T (96.6%). Being phylogenetic, it was most closely related to Aeromicrobium halocynthiae JCM 15749T. The G+C content of the genomic DNA was 70.3 mol%. The diagnostic diamino acid of the cell wall peptidoglycan was LL-diaminopimelic acid. The predominant menaquinone was menaquinone MK-8 (H4) and MK-7 (H4) was a minor compound. The major cellular fatty acids were C14:0, C16:0, C18:1 ω9c and summed feature 4 (C16:1 ω7c/C15:0 iso 2-OH). All these data supported the affiliation of strain Gsoil 137T to the genus Aeromicrobium. The results of physiological and biochemical tests enabled strain Gsoil 137T to be differentiated genotypically and phenotypically from currently known Aeromicrobium species. Therefore, strain Gsoil 137T represents a novel species of the genus Aeromicrobium, for which the name Aeromicrobium panacisoli sp. nov. is proposed. The type strain is Gsoil 137T (= KCTC 19130T = DSM 17940T = CCUG 52475T).}, } @article {pmid29289545, year = {2018}, author = {Rodgers, R and Roach, JL and Reid, NM and Whitehead, A and Duvernell, DD}, title = {Phylogenomic analysis of Fundulidae (Teleostei: Cyprinodotiformes) using RNA-sequencing data.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {150-157}, doi = {10.1016/j.ympev.2017.12.030}, pmid = {29289545}, issn = {1095-9513}, support = {S10 RR029668/RR/NCRR NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Fundulidae/*genetics ; Genomics/*methods ; Likelihood Functions ; *Phylogeny ; RNA/genetics ; Sequence Analysis, RNA/*methods ; }, abstract = {Fishes of the New World cyprinodontiform family Fundulidae display a wide variety of tolerance to environmental conditions, making them a valuable model system for comparative, evolutionary, and environmental studies. Despite numerous attempts to resolve the phylogenetic relationships of family Fundulidae, the basal structure of the phylogeny remains unresolved. The lack of a robust and fully resolved phylogeny for family Fundulidae and its most speciose genus Fundulus is an impediment to future research. This study utilized novel RNA-sequencing data for phylogenetic inference among16 members of Fundulidae to better refine the basal nodes of the family and confront long-standing questions regarding (1) the monophyletic status of genus Fundulus, and validity of the Lucania and recently synonymized Adinia genera; (2) the relationship of the west coast endemic Fundulus parvipinnis and F. lima to other Fundulus species; and (3) the validity of subgeneric classifications. In addition, previously published nuclear gene sequences for 32 Fundulidae species were re-analyzed in combination with novel RNA-sequencing data. Maximum likelihood and Bayesian analyses generated identical phylogenies with strong statistical support at nearly all nodes, demonstrating the utility of RNA-sequencing data in constructing robust phylogenies not achievable by previous methods. While many past hypothesized evolutionary relationships for Fundulidae were reinforced, several alternative relationships are hypothesized at basal nodes resulting in a re-analysis of the deeper structure of family Fundulidae. These results reveal family Fundulidae as a paraphyletic grouping of members of genus Fundulus and Lucania and supports the previous synonymy of genus Adinia with genus Fundulus.}, } @article {pmid29289544, year = {2018}, author = {Wainwright, PC and Santini, F and Bellwood, DR and Robertson, DR and Rocha, LA and Alfaro, ME}, title = {Phylogenetics and geography of speciation in New World Halichoeres wrasses.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {35-45}, doi = {10.1016/j.ympev.2017.12.028}, pmid = {29289544}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Ecosystem ; *Genetic Speciation ; *Geography ; Models, Biological ; Panama ; Perciformes/*classification/*genetics ; *Phylogeny ; Phylogeography ; Species Specificity ; Time Factors ; }, abstract = {The New World Halichoeres comprises about 30 small to medium sized wrasse species that are prominent members of reef communities throughout the tropical Western Atlantic and Eastern Pacific. We conducted a phylogenetic analysis of this group and related lineages using new and previously published sequence data. We estimated divergence times, evaluated the monophyly of this group, their relationship to other labrids, as well as the time-course and geography of speciation. These analyses show that all members of New World Halichoeres form a monophyletic group that includes Oxyjulis and Sagittalarva. New World Halichoeres is one of numerous labrid groups that appear to have radiated rapidly about 32 Ma and form a large polytomy within the julidine wrasses. We reconstruct the tropical Western Atlantic to be the ancestral area of New World Halichoeres, with four invasions of the Eastern Pacific and one reversal from East Pacific to Western Atlantic. These five speciation events were spread across the history of the group, with none corresponding closely to the time of the closure of the Isthmus of Panama. Three speciation events within the Atlantic occurred across the Orinoco-Amazon outflow and within the Pacific, five involve splits between lineages that occupy coastal reef systems and offshore islands. Of eight sister species pairs, seven show complete allopatry and one is fully sympatric.}, } @article {pmid29289422, year = {2018}, author = {Zhong, G}, title = {Chlamydia Spreading from the Genital Tract to the Gastrointestinal Tract - A Two-Hit Hypothesis.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {611-623}, pmid = {29289422}, issn = {1878-4380}, support = {R01 AI047997/AI/NIAID NIH HHS/United States ; R01 AI121989/AI/NIAID NIH HHS/United States ; R21 AI105712/AI/NIAID NIH HHS/United States ; }, abstract = {Chlamydia trachomatis, a leading bacterial cause of sexually transmitted infection-induced infertility, is frequently detected in the gastrointestinal tract. Chlamydia muridarum, a model pathogen for investigating C. trachomatis pathogenesis, readily spreads from the mouse genital tract to the gastrointestinal tract, establishing long-lasting colonization. C. muridarum mutants, despite their ability to activate acute oviduct inflammation, are attenuated in inducing tubal fibrosis and are no longer able to colonize the gastrointestinal tract, suggesting that the spread of C. muridarum to the gastrointestinal tract may contribute to its pathogenicity in the upper genital tract. However, gastrointestinal C. muridarum cannot directly autoinoculate the genital tract. Both antigen-specific CD8+ T cells and profibrotic cytokines, such as TNFα and IL-13, are essential for C. muridarum to induce tubal fibrosis; this may be induced by the gastrointestinal C. muridarum, as a second hit, to transmucosally convert tubal repairing - initiated by C. muridarum infection of tubal epithelial cells (serving as the first hit) - into pathogenic fibrosis. Testing the two-hit mouse model should both add new knowledge to the growing list of mechanisms by which gastrointestinal microbes contribute to pathologies in extragastrointestinal tissues and provide information for investigating the potential role of gastrointestinal C. trachomatis in human chlamydial pathogenesis.}, } @article {pmid29289355, year = {2018}, author = {Díez-Del-Molino, D and Sánchez-Barreiro, F and Barnes, I and Gilbert, MTP and Dalén, L}, title = {Quantifying Temporal Genomic Erosion in Endangered Species.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {176-185}, doi = {10.1016/j.tree.2017.12.002}, pmid = {29289355}, issn = {1872-8383}, mesh = {*Endangered Species ; Extinction, Biological ; *Genetic Variation ; *Genome ; Genomics/*methods ; Inbreeding ; }, abstract = {Many species have undergone dramatic population size declines over the past centuries. Although stochastic genetic processes during and after such declines are thought to elevate the risk of extinction, comparative analyses of genomic data from several endangered species suggest little concordance between genome-wide diversity and current population sizes. This is likely because species-specific life-history traits and ancient bottlenecks overshadow the genetic effect of recent demographic declines. Therefore, we advocate that temporal sampling of genomic data provides a more accurate approach to quantify genetic threats in endangered species. Specifically, genomic data from predecline museum specimens will provide valuable baseline data that enable accurate estimation of recent decreases in genome-wide diversity, increases in inbreeding levels, and accumulation of deleterious genetic variation.}, } @article {pmid29289354, year = {2018}, author = {Turbek, SP and Scordato, ESC and Safran, RJ}, title = {The Role of Seasonal Migration in Population Divergence and Reproductive Isolation.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {164-175}, doi = {10.1016/j.tree.2017.11.008}, pmid = {29289354}, issn = {1872-8383}, mesh = {*Animal Migration ; Animals ; Biological Evolution ; *Gene Flow ; Invertebrates/genetics/*physiology ; Phenotype ; *Reproductive Isolation ; Seasons ; Vertebrates/genetics/*physiology ; }, abstract = {Seasonal journeys between breeding and non-breeding habitat are undertaken by a diverse array of animals. Parallel developments in tracking and genomic methods are enabling finer resolution of these movements and their role in the evolutionary process. Evidence from allopatric and co-occurring breeding populations indicates that variation in migratory behavior is often associated with genetic differentiation. While assortative mating and selection against hybrids due to divergent migratory phenotypes can contribute to reproductive isolation, the details of these mechanisms remain unclear. Here we identify gaps in our understanding of the role of seasonal migration in the speciation process and propose a framework to test the relative significance of reproductive barriers associated with variation in migratory behavior that might underlie population differentiation.}, } @article {pmid29289347, year = {2018}, author = {Lasek, AW and Chen, H and Chen, WY}, title = {Releasing Addiction Memories Trapped in Perineuronal Nets.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {197-208}, pmid = {29289347}, issn = {0168-9525}, support = {P50 AA022538/AA/NIAAA NIH HHS/United States ; R01 DA033429/DA/NIDA NIH HHS/United States ; U01 AA020912/AA/NIAAA NIH HHS/United States ; }, mesh = {Animals ; Brain/physiopathology ; Extracellular Matrix/physiology ; Humans ; Memory/*physiology ; Models, Neurological ; Nerve Net/*physiopathology ; Neuronal Plasticity/physiology ; Neurons/*physiology ; Substance-Related Disorders/*physiopathology ; }, abstract = {Drug addiction can be conceptualized at a basic level as maladaptive learning and memory. Addictive substances elicit changes in brain circuitry involved in reward, cognition, and emotional state, leading to the formation and persistence of strong drug-associated memories that lead to craving and relapse. Recently, perineuronal nets (PNNs), extracellular matrix (ECM) structures surrounding neurons, have emerged as regulators of learning, memory, and addiction behaviors. PNNs do not merely provide structural support to neurons but are dynamically remodeled in an experience-dependent manner by metalloproteinases. They function in various brain regions through constituent proteins such as brevican that are implicated in neural plasticity. Understanding the function of PNN components in memory processes may lead to new therapeutic approaches to treating addiction.}, } @article {pmid29288798, year = {2018}, author = {Li, H and He, Y and Jiang, J and Liu, Z and Li, C}, title = {Molecular systematics and phylogenetic analysis of the Asian endemic freshwater sleepers (Gobiiformes: Odontobutidae).}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {1-11}, doi = {10.1016/j.ympev.2017.12.026}, pmid = {29288798}, issn = {1095-9513}, mesh = {Animals ; Bone and Bones/anatomy & histology ; Calibration ; China ; Fossils ; *Fresh Water ; Likelihood Functions ; Perciformes/anatomy & histology/*classification ; *Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Species Specificity ; Time Factors ; }, abstract = {The Odontobutidae is a group of freshwater sleepers endemic to East and Southeast Asia. The composition of the Odontobutidae is controversial and the systematics position of some species (e.g. Philypnus chalmersi) remains unknown. Phylogenetic relationship among the odontobutids has never been really tested due to the lack of informative morphological characters, and that molecular data have not been collected in many species. Here, we sampled 41 specimens, representing all known genera of the Odontobutidae except the Laotian genus Terateleotris, in addition to a disputable odontobutid species, Philypnus chalmersi and 14 outgroups (six families). We collected sequence data of 4434 single-copy nuclear coding loci using gene capture and Illumina sequencing. A robust phylogeny of the odontobutids and outgroups was built, confirming that the Odontobutidae is monophyletic and sister to the Rhyacichthyidae. We verified that Neodontobutis, Sineleotris and Philypnus chalmersi are members of the Odontobutidae based on the resulting phylogeny as well as patterns of pectoral girdle examined by X-ray microtomography. We proposed a new genus Microdous for Philypnus chalmersi based on the new morphological and molecular evidences. The family of the Odontobutidae can be divided into two clades: Microdous (=Philypnus) sister to a group consisting of Micropercops and Sineleotris, and Odontobutis sister to a group unifying Perccottus and Neodontobutis. Divergence time among the odontobutids was estimated based on 100 most clock-like loci and three fossil calibration points using BEAST. Ancestral range of the family was reconstructed using Reconstruct Ancestral States in Phylogenies (RASP) and BioGeoBEARS. The results suggest that the common ancestor of the odontobutids originated around 30.8 Ma (20.7-42.0 Ma, 95% HPDs) in South China. Orogeny, climatic change and river capture might account for diversification and current distribution of the odontobutids.}, } @article {pmid29288562, year = {2018}, author = {Gipson, SAY and Hall, MD}, title = {Interactions between host sex and age of exposure modify the virulence-transmission trade-off.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {428-437}, doi = {10.1111/jeb.13237}, pmid = {29288562}, issn = {1420-9101}, abstract = {The patterns of immunity conferred by host sex or age represent two sources of host heterogeneity that can potentially shape the evolutionary trajectory of disease. With each host sex or age encountered, a pathogen's optimal exploitative strategy may change, leading to considerable variation in expression of pathogen transmission and virulence. To date, these host characteristics have been studied in the context of host fitness alone, overlooking the effects of host sex and age on the fundamental virulence-transmission trade-off faced by pathogens. Here, we explicitly address the interaction of these characteristics and find that host sex and age at exposure to a pathogen affect age-specific patterns of mortality and the balance between pathogen transmission and virulence. When infecting age-structured male and female Daphnia magna with different genotypes of Pasteuria ramosa, we found that infection increased mortality rates across all age classes for females, whereas mortality only increased in the earliest age class for males. Female hosts allowed a variety of trade-offs between transmission and virulence to arise with each age and pathogen genotype. In contrast, this variation was dampened in males, with pathogens exhibiting declines in both virulence and transmission with increasing host age. Our results suggest that differences in exploitation potential of males and females to a pathogen can interact with host age to allow different virulence strategies to coexist, and illustrate the potential for these widespread sources of host heterogeneity to direct the evolution of disease in natural populations.}, } @article {pmid29288541, year = {2018}, author = {Sofonea, MT and Aldakak, L and Boullosa, LFVV and Alizon, S}, title = {Can Ebola virus evolve to be less virulent in humans?.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {382-392}, doi = {10.1111/jeb.13229}, pmid = {29288541}, issn = {1420-9101}, abstract = {Understanding Ebola virus (EBOV) virulence evolution not only is timely but also raises specific questions because it causes one of the most virulent human infections and it is capable of transmission after the death of its host. Using a compartmental epidemiological model that captures three transmission routes (by regular contact, via dead bodies and by sexual contact), we infer the evolutionary dynamics of case fatality ratio on the scale of an outbreak and in the long term. Our major finding is that the virus's specific life cycle imposes selection for high levels of virulence and that this pattern is robust to parameter variations in biological ranges. In addition to shedding a new light on the ultimate causes of EBOV's high virulence, these results generate testable predictions and contribute to informing public health policies. In particular, burial management stands out as the most appropriate intervention since it decreases the R0 of the epidemics, while imposing selection for less virulent strains.}, } @article {pmid29288225, year = {2018}, author = {Risk, BB and Zhu, H}, title = {Note on bias from averaging repeated measurements in heritability studies.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E122}, pmid = {29288225}, issn = {1091-6490}, support = {R01 MH086633/MH/NIMH NIH HHS/United States ; T32 MH106440/MH/NIMH NIH HHS/United States ; }, mesh = {*Bias ; *Wills ; }, } @article {pmid29288224, year = {2018}, author = {Ge, T and Holmes, AJ and Buckner, RL and Smoller, JW and Sabuncu, MR}, title = {Reply to Risk and Zhu: Mixed-effects modeling as a principled approach to heritability analysis with repeat measurements.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E123}, pmid = {29288224}, issn = {1091-6490}, support = {K01 MH099232/MH/NIMH NIH HHS/United States ; }, mesh = {*Phenotype ; *Wills ; }, } @article {pmid29288223, year = {2018}, author = {Plewis, I}, title = {Analyzing Indian farmer suicide rates.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E117}, pmid = {29288223}, issn = {1091-6490}, mesh = {Asian Continental Ancestry Group ; *Farmers ; Humans ; Indians, North American ; Risk Factors ; *Suicide ; }, } @article {pmid29288222, year = {2018}, author = {Das, S}, title = {Unfounded assumptions in linking crop-damaging temperature and suicide in India.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E116}, pmid = {29288222}, issn = {1091-6490}, mesh = {Crops, Agricultural ; India ; *Suicide ; *Temperature ; }, } @article {pmid29288221, year = {2018}, author = {Murari, KK and Jayaraman, T and Swaminathan, M}, title = {Climate change and agricultural suicides in India.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E115}, pmid = {29288221}, issn = {1091-6490}, mesh = {*Agriculture ; *Climate Change ; Crops, Agricultural ; India ; Suicide ; }, } @article {pmid29288220, year = {2018}, author = {Carleton, TA}, title = {Reply to Plewis, Murari et al., and Das: The suicide-temperature link in India and the evidence of an agricultural channel are robust.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E118-E121}, pmid = {29288220}, issn = {1091-6490}, mesh = {Agriculture ; India ; *Suicide ; *Temperature ; }, } @article {pmid29288219, year = {2018}, author = {Field, DJ}, title = {Endless skulls most beautiful.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {448-450}, pmid = {29288219}, issn = {1091-6490}, mesh = {*Beauty ; *Skull ; }, } @article {pmid29288218, year = {2018}, author = {Willer Gold, J and Arsenijević, B and Batinić, M and Becker, M and Čordalija, N and Kresić, M and Leko, N and Marušič, FL and Milićev, T and Milićević, N and Mitić, I and Peti-Stantić, A and Stanković, B and Šuligoj, T and Tušek, J and Nevins, A}, title = {When linearity prevails over hierarchy in syntax.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {495-500}, pmid = {29288218}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Female ; Humans ; *Language ; Linguistics ; Male ; Psycholinguistics ; Young Adult ; }, abstract = {Hierarchical structure has been cherished as a grammatical universal. We use experimental methods to show where linear order is also a relevant syntactic relation. An identical methodology and design were used across six research sites on South Slavic languages. Experimental results show that in certain configurations, grammatical production can in fact favor linear order over hierarchical structure. However, these findings are limited to coordinate structures and distinct from the kind of production errors found with comparable configurations such as "attraction" errors. The results demonstrate that agreement morphology may be computed in a series of steps, one of which is partly independent from syntactic hierarchy.}, } @article {pmid29288217, year = {2018}, author = {Adolphs, R and Gläscher, J and Tranel, D}, title = {Searching for the neural causes of criminal behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {451-452}, pmid = {29288217}, issn = {1091-6490}, support = {P50 MH094258/MH/NIMH NIH HHS/United States ; }, mesh = {*Crime ; *Criminal Behavior ; }, } @article {pmid29288216, year = {2018}, author = {Kirchman, DL}, title = {Microbial proteins for organic material degradation in the deep ocean.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {445-447}, pmid = {29288216}, issn = {1091-6490}, mesh = {Carbon/*analysis ; Oceans and Seas ; *Seawater ; }, } @article {pmid29288215, year = {2018}, author = {Zhao, L and Cai, H and Su, Z and Wang, L and Huang, X and Zhang, M and Chen, P and Dai, X and Zhao, H and Palanivelu, R and Chen, X and Qin, Y}, title = {KLU suppresses megasporocyte cell fate through SWR1-mediated activation of WRKY28 expression in Arabidopsis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E526-E535}, pmid = {29288215}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Arabidopsis/genetics/*physiology ; Arabidopsis Proteins/genetics/*metabolism ; Cytochrome P-450 Enzyme System/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Gene Expression Regulation, Plant/*physiology ; Histones/genetics/metabolism ; Mutation ; Ovule/growth & development/metabolism ; Plant Components, Aerial/physiology ; Plant Roots/physiology ; RNA, Plant/genetics/metabolism ; Transcription Factors/genetics/*metabolism ; }, abstract = {Germ-line specification is essential for sexual reproduction. In the ovules of most flowering plants, only a single hypodermal cell enlarges and differentiates into a megaspore mother cell (MMC), the founder cell of the female germ-line lineage. The molecular mechanisms restricting MMC specification to a single cell remain elusive. We show that the Arabidopsis transcription factor WRKY28 is exclusively expressed in hypodermal somatic cells surrounding the MMC and is required to repress these cells from acquiring MMC-like cell identity. In this process, the SWR1 chromatin remodeling complex mediates the incorporation of the histone variant H2A.Z at the WRKY28 locus. Moreover, the cytochrome P450 gene KLU, expressed in inner integument primordia, non-cell-autonomously promotes WRKY28 expression through H2A.Z deposition at WRKY28. Taken together, our findings show how somatic cells in ovule primordia cooperatively use chromatin remodeling to restrict germ-line cell specification to a single cell.}, } @article {pmid29288080, year = {2018}, author = {Colebunders, R and Nelson Siewe, FJ and Hotterbeekx, A}, title = {Onchocerciasis-Associated Epilepsy, an Additional Reason for Strengthening Onchocerciasis Elimination Programs.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {208-216}, doi = {10.1016/j.pt.2017.11.009}, pmid = {29288080}, issn = {1471-5007}, mesh = {Animals ; *Disease Eradication ; Epilepsy/*etiology ; Humans ; Onchocerca volvulus ; Onchocerciasis/*complications/pathology ; Seizures ; }, abstract = {A high prevalence of epilepsy has been observed in onchocerciasis-endemic regions with high onchocerciasis transmission. Recent epidemiological studies suggest that Onchocerca volvulus infection is the trigger causing the seizures, which appear in previously healthy children between the ages of 3 and 18 years. Persons with onchocerciasis-associated epilepsy present with a wide spectrum of seizures, including atonic and myoclonic neck seizures; but also absences and most frequently generalized tonic-clonic seizures. Often individuals present with intellectual disabilities and psychiatric disorders and occasionally with 'Nakalanga' features such as severe stunting with delayed or absent external signs of sexual development. Onchocerciasis-associated epilepsy, because of its importance as a public health problem, is an additional reason for strengthening onchocerciasis elimination programs.}, } @article {pmid29287898, year = {2018}, author = {Scheele, BC and Foster, CN and Banks, SC and Lindenmayer, DB}, title = {The Role of Biotic Interactions in the Niche Reduction Hypothesis: A Reply to Doherty and Driscoll.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {148-149}, doi = {10.1016/j.tree.2017.12.001}, pmid = {29287898}, issn = {1872-8383}, mesh = {*Ecosystem ; *Models, Biological ; }, } @article {pmid29287897, year = {2018}, author = {Bernatchez, L and Wellenreuther, M}, title = {Synergistic Integration of Genomics and Ecoevolutionary Dynamics for Sustainable Fisheries: A Reply to Kuparinen and Uusi-Heikkilä.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {308-310}, doi = {10.1016/j.tree.2017.12.005}, pmid = {29287897}, issn = {1872-8383}, mesh = {Conservation of Natural Resources ; Ecosystem ; *Fisheries ; Fishes ; *Genomics ; Population Dynamics ; }, } @article {pmid29287832, year = {2018}, author = {Eckerle, S and Ringler, M and Lecaudey, V and Nitschke, R and Driever, W}, title = {Progesterone modulates microtubule dynamics and epiboly progression during zebrafish gastrulation.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {249-266}, doi = {10.1016/j.ydbio.2017.12.016}, pmid = {29287832}, issn = {1095-564X}, mesh = {Animals ; Gastrula/*embryology ; Gastrulation/*drug effects/physiology ; Microtubules/genetics/*metabolism ; Progesterone/*pharmacology ; Zebrafish/*embryology/genetics ; }, abstract = {Control of microtubule dynamics is crucial for cell migration. We analyzed regulation of microtubule network dynamics in the zebrafish yolk cell during epiboly, the earliest coordinated gastrulation movement. We labeled microtubules with EMTB-3GFP and EB3-mCherry to visualize and measure microtubule dynamics by TIRF microscopy live imaging. Yolk cell microtubules dynamics is temporally modulated during epiboly progression. We used maternal zygotic Pou5f3 mutant (MZspg) embryos, which develop strong distortions of microtubule network organization and epiboly retardation, to investigate genetic control of microtubule dynamics. In MZspg embryos, microtubule plus-end growth tracks move slower and are less straight compared to wild-type. MZspg embryos have altered steroidogenic enzyme expression, resulting in increased pregnenolone and reduced progesterone levels. We show that progesterone positively affects microtubule plus-end growth and track straightness. Progesterone may thus act as a non-cell-autonomous regulator of microtubule dynamics across the large yolk cell, and may adjust differing demands on microtubule dynamics and stability during initiation and progression phases of epiboly.}, } @article {pmid29287128, year = {2018}, author = {Wang, JY and Liao, WB}, title = {Digest: Ontogenesis and evolutionary allometry shape divergent evolution of genitalia in female cetaceans.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {404-405}, doi = {10.1111/evo.13414}, pmid = {29287128}, issn = {1558-5646}, } @article {pmid29285829, year = {2018}, author = {de Villemereuil, P and Morrissey, MB and Nakagawa, S and Schielzeth, H}, title = {Fixed-effect variance and the estimation of repeatabilities and heritabilities: issues and solutions.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {621-632}, doi = {10.1111/jeb.13232}, pmid = {29285829}, issn = {1420-9101}, abstract = {Linear mixed-effects models are frequently used for estimating quantitative genetic parameters, including the heritability, as well as the repeatability, of traits. Heritability acts as a filter that determines how efficiently phenotypic selection translates into evolutionary change, whereas repeatability informs us about the individual consistency of phenotypic traits. As quantities of biological interest, it is important that the denominator, the phenotypic variance in both cases, reflects the amount of phenotypic variance in the relevant ecological setting. The current practice of quantifying heritabilities and repeatabilities from mixed-effects models frequently deprives their denominator of variance explained by fixed effects (often leading to upward bias of heritabilities and repeatabilities), and it has been suggested to omit fixed effects when estimating heritabilities in particular. We advocate an alternative option of fitting models incorporating all relevant effects, while including the variance explained by fixed effects into the estimation of the phenotypic variance. The approach is easily implemented and allows optimizing the estimation of phenotypic variance, for example by the exclusion of variance arising from experimental design effects while still including all biologically relevant sources of variation. We address the estimation and interpretation of heritabilities in situations in which potential covariates are themselves heritable traits of the organism. Furthermore, we discuss complications that arise in generalized and nonlinear mixed models with fixed effects. In these cases, the variance parameters on the data scale depend on the location of the intercept and hence on the scaling of the fixed effects. Integration over the biologically relevant range of fixed effects offers a preferred solution in those situations.}, } @article {pmid29285828, year = {2018}, author = {Puttick, MN}, title = {Mixed evidence for early bursts of morphological evolution in extant clades.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {502-515}, doi = {10.1111/jeb.13236}, pmid = {29285828}, issn = {1420-9101}, abstract = {Macroevolutionary theory predicts high rates of evolution should occur early in a clade's history as species exploit ecological opportunity. Evidence from the fossil record has shown a high prevalence of early bursts in morphological evolution, but recent work has provided little evidence for early high rates in the evolution of extant clades. Here, I test the prevalence of early bursts in extant data using phylogenetic comparative methods. Existing models are extended to allow a shift from a background Brownian motion (BM) process to an early burst process within subclades of phylogenies, rather than an early burst being applied to an entire phylogenetic tree. This nested early burst model is compared to other modes of evolution that can occur within subclades, such as evolution with a constraint (Ornstein-Uhlenbeck model) and nested BM rate shift models. These relaxed models are validated using simulations and then are applied to body size evolution of three major clades of amniotes (mammals, squamates and aves) at different levels of taxonomic organization (order, family). Applying these unconstrained models greatly increases the support for early bursts within nested subclades, and so early bursts are the most common model of evolution when only one shift is analysed. However, the relative fit of early burst models is worse than models that allow for multiple shifts of the BM or OU process. No single-shift or homogenous model is superior to models of multiple shifts in BM or OU evolution, but the patterns shown by these multirate models are generally congruent with patterns expected from early bursts.}, } @article {pmid29284755, year = {2018}, author = {Dong, S and Xie, JW and Zhou, JL and Zheng, Z and Luo, A}, title = {LAMOST telescope reveals that Neptunian cousins of hot Jupiters are mostly single offspring of stars that are rich in heavy elements.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {266-271}, pmid = {29284755}, issn = {1091-6490}, abstract = {We discover a population of short-period, Neptune-size planets sharing key similarities with hot Jupiters: both populations are preferentially hosted by metal-rich stars, and both are preferentially found in Kepler systems with single-transiting planets. We use accurate Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) Data Release 4 (DR4) stellar parameters for main-sequence stars to study the distributions of short-period [Formula: see text] Kepler planets as a function of host star metallicity. The radius distribution of planets around metal-rich stars is more "puffed up" compared with that around metal-poor hosts. In two period-radius regimes, planets preferentially reside around metal-rich stars, while there are hardly any planets around metal-poor stars. One is the well-known hot Jupiters, and the other one is a population of Neptune-size planets ([Formula: see text]), dubbed "Hoptunes." Also like hot Jupiters, Hoptunes occur more frequently in systems with single-transiting planets although the fraction of Hoptunes occurring in multiples is larger than that of hot Jupiters. About [Formula: see text] of solar-type stars host Hoptunes, and the frequencies of Hoptunes and hot Jupiters increase with consistent trends as a function of [Fe/H]. In the planet radius distribution, hot Jupiters and Hoptunes are separated by a "valley" at approximately Saturn size (in the range of [Formula: see text]), and this "hot-Saturn valley" represents approximately an order-of-magnitude decrease in planet frequency compared with hot Jupiters and Hoptunes. The empirical "kinship" between Hoptunes and hot Jupiters suggests likely common processes (migration and/or formation) responsible for their existence.}, } @article {pmid29284754, year = {2018}, author = {Grybchuk, D and Akopyants, NS and Kostygov, AY and Konovalovas, A and Lye, LF and Dobson, DE and Zangger, H and Fasel, N and Butenko, A and Frolov, AO and Votýpka, J and d'Avila-Levy, CM and Kulich, P and Moravcová, J and Plevka, P and Rogozin, IB and Serva, S and Lukeš, J and Beverley, SM and Yurchenko, V}, title = {Viral discovery and diversity in trypanosomatid protozoa with a focus on relatives of the human parasite Leishmania.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E506-E515}, pmid = {29284754}, issn = {1091-6490}, support = {R01 AI029646/AI/NIAID NIH HHS/United States ; R56 AI099364/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Euglenozoa Infections/parasitology/veterinary ; Genetic Variation ; Host Specificity ; Host-Pathogen Interactions ; Humans ; Phylogeny ; RNA Viruses/*genetics/*isolation & purification ; Trypanosomatina/*virology ; }, abstract = {Knowledge of viral diversity is expanding greatly, but many lineages remain underexplored. We surveyed RNA viruses in 52 cultured monoxenous relatives of the human parasite Leishmania (Crithidia and Leptomonas), as well as plant-infecting PhytomonasLeptomonas pyrrhocoris was a hotbed for viral discovery, carrying a virus (Leptomonas pyrrhocoris ostravirus 1) with a highly divergent RNA-dependent RNA polymerase missed by conventional BLAST searches, an emergent clade of tombus-like viruses, and an example of viral endogenization. A deep-branching clade of trypanosomatid narnaviruses was found, notable as Leptomonas seymouri bearing Narna-like virus 1 (LepseyNLV1) have been reported in cultures recovered from patients with visceral leishmaniasis. A deep-branching trypanosomatid viral lineage showing strong affinities to bunyaviruses was termed "Leishbunyavirus" (LBV) and judged sufficiently distinct to warrant assignment within a proposed family termed "Leishbunyaviridae" Numerous relatives of trypanosomatid viruses were found in insect metatranscriptomic surveys, which likely arise from trypanosomatid microbiota. Despite extensive sampling we found no relatives of the totivirus Leishmaniavirus (LRV1/2), implying that it was acquired at about the same time the Leishmania became able to parasitize vertebrates. As viruses were found in over a quarter of isolates tested, many more are likely to be found in the >600 unsurveyed trypanosomatid species. Viral loss was occasionally observed in culture, providing potentially isogenic virus-free lines enabling studies probing the biological role of trypanosomatid viruses. These data shed important insights on the emergence of viruses within an important trypanosomatid clade relevant to human disease.}, } @article {pmid29284753, year = {2018}, author = {Zhang, R and Kumar, N and Ross, JL and Gardel, ML and de Pablo, JJ}, title = {Interplay of structure, elasticity, and dynamics in actin-based nematic materials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E124-E133}, pmid = {29284753}, issn = {1091-6490}, mesh = {Actin Cytoskeleton/*chemistry ; Actins/*chemistry ; Algorithms ; Animals ; Biopolymers/*chemistry ; *Elasticity ; Hydrodynamics ; Liquid Crystals/*chemistry ; Models, Chemical ; Muscle, Skeletal/chemistry ; Rabbits ; Thermodynamics ; }, abstract = {Achieving control and tunability of lyotropic materials has been a long-standing goal of liquid crystal research. Here we show that the elasticity of a liquid crystal system consisting of a dense suspension of semiflexible biopolymers can be manipulated over a relatively wide range of elastic moduli. Specifically, thin films of actin filaments are assembled at an oil-water interface. At sufficiently high concentrations, one observes the formation of a nematic phase riddled with [Formula: see text] topological defects, characteristic of a two-dimensional nematic system. As the average filament length increases, the defect morphology transitions from a U shape into a V shape, indicating the relative increase of the material's bend over splay modulus. Furthermore, through the sparse addition of rigid microtubule filaments, one can gain additional control over the liquid crystal's elasticity. We show how the material's bend constant can be raised linearly as a function of microtubule filament density, and present a simple means to extract absolute values of the elastic moduli from purely optical observations. Finally, we demonstrate that it is possible to predict not only the static structure of the material, including its topological defects, but also the evolution of the system into dynamically arrested states. Despite the nonequilibrium nature of the system, our continuum model, which couples structure and hydrodynamics, is able to capture the annihilation and movement of defects over long time scales. Thus, we have experimentally realized a lyotropic liquid crystal system that can be truly engineered, with tunable mechanical properties, and a theoretical framework to capture its structure, mechanics, and dynamics.}, } @article {pmid29284752, year = {2018}, author = {Baggen, J and Hurdiss, DL and Zocher, G and Mistry, N and Roberts, RW and Slager, JJ and Guo, H and van Vliet, ALW and Wahedi, M and Benschop, K and Duizer, E and de Haan, CAM and de Vries, E and Casasnovas, JM and de Groot, RJ and Arnberg, N and Stehle, T and Ranson, NA and Thibaut, HJ and van Kuppeveld, FJM}, title = {Role of enhanced receptor engagement in the evolution of a pandemic acute hemorrhagic conjunctivitis virus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {397-402}, pmid = {29284752}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 102572/B/13/Z//Wellcome Trust/United Kingdom ; 108466/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Amino Acid Sequence ; Capsid Proteins/genetics/metabolism ; Conjunctivitis, Acute Hemorrhagic/epidemiology/*metabolism/virology ; Cryoelectron Microscopy ; Disease Outbreaks ; Enterovirus C, Human/genetics/*metabolism/physiology ; Humans ; Intercellular Adhesion Molecule-1/chemistry/*metabolism ; Mutation ; N-Acetylneuraminic Acid/metabolism ; Pandemics ; Phylogeny ; Protein Binding ; Receptors, Virus/chemistry/*metabolism ; Sequence Homology, Amino Acid ; Viral Tropism/physiology ; }, abstract = {Acute hemorrhagic conjunctivitis (AHC) is a painful, contagious eye disease, with millions of cases in the last decades. Coxsackievirus A24 (CV-A24) was not originally associated with human disease, but in 1970 a pathogenic "variant" (CV-A24v) emerged, which is now the main cause of AHC. Initially, this variant circulated only in Southeast Asia, but it later spread worldwide, accounting for numerous AHC outbreaks and two pandemics. While both CV-A24 variant and nonvariant strains still circulate in humans, only variant strains cause AHC for reasons that are yet unknown. Since receptors are important determinants of viral tropism, we set out to map the CV-A24 receptor repertoire and establish whether changes in receptor preference have led to the increased pathogenicity and rapid spread of CV-A24v. Here, we identify ICAM-1 as an essential receptor for both AHC-causing and non-AHC strains. We provide a high-resolution cryo-EM structure of a virus-ICAM-1 complex, which revealed critical ICAM-1-binding residues. These data could help identify a possible conserved mode of receptor engagement among ICAM-1-binding enteroviruses and rhinoviruses. Moreover, we identify a single capsid substitution that has been adopted by all pandemic CV-A24v strains and we reveal that this adaptation enhances the capacity of CV-A24v to bind sialic acid. Our data elucidate the CV-A24v receptor repertoire and point to a role of enhanced receptor engagement in the adaptation to the eye, possibly enabling pandemic spread.}, } @article {pmid29284751, year = {2018}, author = {Li, R and Xie, Q and Wang, YD and Liu, W and Wang, M and Wu, G and Li, X and Zhang, M and Lu, Z and Geng, C and Zhu, T}, title = {Unraveling submicron-scale mechanical heterogeneity by three-dimensional X-ray microdiffraction.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {483-488}, pmid = {29284751}, issn = {1091-6490}, abstract = {Shear banding is a ubiquitous phenomenon of severe plastic deformation, and damage accumulation in shear bands often results in the catastrophic failure of a material. Despite extensive studies, the microscopic mechanisms of strain localization and deformation damage in shear bands remain elusive due to their spatial-temporal complexities embedded in bulk materials. Here we conducted synchrotron-based X-ray microdiffraction (μXRD) experiments to map out the 3D lattice strain field with a submicron resolution around fatigue shear bands in a stainless steel. Both in situ and postmortem μXRD results revealed large lattice strain gradients at intersections of the primary and secondary shear bands. Such strain gradients resulted in severe mechanical heterogeneities across the fatigue shear bands, leading to reduced fatigue limits in the high-cycle regime. The ability to spatially quantify the localized strain gradients with submicron resolution through μXRD opens opportunities for understanding the microscopic mechanisms of damage and failure in bulk materials.}, } @article {pmid29284750, year = {2018}, author = {Louis, T and Stahl, A and Boto, T and Tomchik, SM}, title = {Cyclic AMP-dependent plasticity underlies rapid changes in odor coding associated with reward learning.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E448-E457}, pmid = {29284750}, issn = {1091-6490}, support = {R00 MH092294/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Conditioning, Classical/*physiology ; Cyclic AMP/*physiology ; Drosophila/physiology ; Drosophila Proteins/genetics/metabolism ; Learning/physiology ; Mushroom Bodies/*physiology ; Neuronal Plasticity/*physiology ; Odorants ; Smell/*physiology ; }, abstract = {Learning and memory rely on dopamine and downstream cAMP-dependent plasticity across diverse organisms. Despite the central role of cAMP signaling, it is not known how cAMP-dependent plasticity drives coherent changes in neuronal physiology that encode the memory trace, or engram. In Drosophila, the mushroom body (MB) is critically involved in olfactory classical conditioning, and cAMP signaling molecules are necessary and sufficient for normal memory in intrinsic MB neurons. To evaluate the role of cAMP-dependent plasticity in learning, we examined how cAMP manipulations and olfactory classical conditioning modulate olfactory responses in the MB with in vivo imaging. Elevating cAMP pharmacologically or optogenetically produced plasticity in MB neurons, altering their responses to odorants. Odor-evoked Ca2+ responses showed net facilitation across anatomical regions. At the single-cell level, neurons exhibited heterogeneous responses to cAMP elevation, suggesting that cAMP drives plasticity to discrete subsets of MB neurons. Olfactory appetitive conditioning enhanced MB odor responses, mimicking the cAMP-dependent plasticity in directionality and magnitude. Elevating cAMP to equivalent levels as appetitive conditioning also produced plasticity, suggesting that the cAMP generated during conditioning affects odor-evoked responses in the MB. Finally, we found that this plasticity was dependent on the Rutabaga type I adenylyl cyclase, linking cAMP-dependent plasticity to behavioral modification. Overall, these data demonstrate that learning produces robust cAMP-dependent plasticity in intrinsic MB neurons, which is biased toward naturalistic reward learning. This suggests that cAMP signaling may serve to modulate intrinsic MB responses toward salient stimuli.}, } @article {pmid29284749, year = {2018}, author = {Liu, H and Dong, P and Ioannou, MS and Li, L and Shea, J and Pasolli, HA and Grimm, JB and Rivlin, PK and Lavis, LD and Koyama, M and Liu, Z}, title = {Visualizing long-term single-molecule dynamics in vivo by stochastic protein labeling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {343-348}, pmid = {29284749}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Binding Sites ; Cell Line, Tumor ; Cell Tracking/*methods ; Cells, Cultured ; Humans ; Kinetics ; Neurons/cytology/*metabolism ; Synaptic Vesicles/*metabolism ; Time-Lapse Imaging/methods ; Transcription Factors/*metabolism ; Zebrafish ; }, abstract = {Our ability to unambiguously image and track individual molecules in live cells is limited by packing of multiple copies of labeled molecules within the resolution limit. Here we devise a universal genetic strategy to precisely control copy number of fluorescently labeled molecules in a cell. This system has a dynamic range of ∼10,000-fold, enabling sparse labeling of proteins expressed at different abundance levels. Combined with photostable labels, this system extends the duration of automated single-molecule tracking by two orders of magnitude. We demonstrate long-term imaging of synaptic vesicle dynamics in cultured neurons as well as in intact zebrafish. We found axon initial segment utilizes a "waterfall" mechanism gating synaptic vesicle transport polarity by promoting anterograde transport processivity. Long-time observation also reveals that transcription factor hops between clustered binding sites in spatially restricted subnuclear regions, suggesting that topological structures in the nucleus shape local gene activities by a sequestering mechanism. This strategy thus greatly expands the spatiotemporal length scales of live-cell single-molecule measurements, enabling new experiments to quantitatively understand complex control of molecular dynamics in vivo.}, } @article {pmid29284748, year = {2018}, author = {Louthan, AM and Pringle, RM and Goheen, JR and Palmer, TM and Morris, WF and Doak, DF}, title = {Aridity weakens population-level effects of multiple species interactions on Hibiscus meyeri.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {543-548}, pmid = {29284748}, issn = {1091-6490}, mesh = {Africa ; Animals ; Climate Change ; Desert Climate ; *Ecosystem ; Herbivory/physiology ; Hibiscus/chemistry/*growth & development/physiology ; Kinetics ; }, abstract = {Predicting how species' abundances and ranges will shift in response to climate change requires a mechanistic understanding of how multiple factors interact to limit population growth. Both abiotic stress and species interactions can limit populations and potentially set range boundaries, but we have a poor understanding of when and where each is most critical. A commonly cited hypothesis, first proposed by Darwin, posits that abiotic factors (e.g., temperature, precipitation) are stronger determinants of range boundaries in apparently abiotically stressful areas ("stress" indicates abiotic factors that reduce population growth), including desert, polar, or high-elevation environments, whereas species interactions (e.g., herbivory, competition) play a stronger role in apparently less stressful environments. We tested a core tenet of this hypothesis-that population growth rate is more strongly affected by species interactions in less stressful areas-using experimental manipulations of species interactions affecting a common herbaceous plant, Hibiscus meyeri (Malvaceae), across an aridity gradient in a semiarid African savanna. Population growth was more strongly affected by four distinct species interactions (competition with herbaceous and shrubby neighbors, herbivory, and pollination) in less stressful mesic areas than in more stressful arid sites. However, contrary to common assumptions, this effect did not arise because of greater density or diversity of interacting species in less stressful areas, but rather because aridity reduced sensitivity of population growth to these interactions. Our work supports classic predictions about the relative strength of factors regulating population growth across stress gradients, but suggests that this pattern results from a previously unappreciated mechanism that may apply to many species worldwide.}, } @article {pmid29284747, year = {2018}, author = {Rinne, P and Hassan, M and Fernandes, C and Han, E and Hennessy, E and Waldman, A and Sharma, P and Soto, D and Leech, R and Malhotra, PA and Bentley, P}, title = {Motor dexterity and strength depend upon integrity of the attention-control system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E536-E545}, pmid = {29284747}, issn = {1091-6490}, support = {//Department of Health/United Kingdom ; }, mesh = {Aged ; Attention/*physiology ; Case-Control Studies ; *Executive Function ; Female ; Humans ; Male ; Memory/physiology ; Middle Aged ; Motor Activity/*physiology ; Psychomotor Performance/*physiology ; Stroke/*physiopathology ; }, abstract = {Attention control (or executive control) is a higher cognitive function involved in response selection and inhibition, through close interactions with the motor system. Here, we tested whether influences of attention control are also seen on lower level motor functions of dexterity and strength-by examining relationships between attention control and motor performance in healthy-aged and hemiparetic-stroke subjects (n = 93 and 167, respectively). Subjects undertook simple-tracking, precision-hold, and maximum force-generation tasks, with each hand. Performance across all tasks correlated strongly with attention control (measured as distractor resistance), independently of factors such as baseline performance, hand use, lesion size, mood, fatigue, or whether distraction was tested during motor or nonmotor cognitive tasks. Critically, asymmetric dissociations occurred in all tasks, in that severe motor impairment coexisted with normal (or impaired) attention control whereas normal motor performance was never associated with impaired attention control (below a task-dependent threshold). This implies that dexterity and force generation require intact attention control. Subsequently, we examined how motor and attention-control performance mapped to lesion location and cerebral functional connectivity. One component of motor performance (common to both arms), as well as attention control, correlated with the anatomical and functional integrity of a cingulo-opercular "salience" network. Independently of this, motor performance difference between arms correlated negatively with the integrity of the primary sensorimotor network and corticospinal tract. These results suggest that the salience network, and its attention-control function, are necessary for virtually all volitional motor acts while its damage contributes significantly to the cardinal motor deficits of stroke.}, } @article {pmid29284746, year = {2018}, author = {Dong, C and Jin, M and Lingam, M and Airapetian, VS and Ma, Y and van der Holst, B}, title = {Atmospheric escape from the TRAPPIST-1 planets and implications for habitability.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {260-265}, pmid = {29284746}, issn = {1091-6490}, abstract = {The presence of an atmosphere over sufficiently long timescales is widely perceived as one of the most prominent criteria associated with planetary surface habitability. We address the crucial question of whether the seven Earth-sized planets transiting the recently discovered ultracool dwarf star TRAPPIST-1 are capable of retaining their atmospheres. To this effect, we carry out numerical simulations to characterize the stellar wind of TRAPPIST-1 and the atmospheric ion escape rates for all of the seven planets. We also estimate the escape rates analytically and demonstrate that they are in good agreement with the numerical results. We conclude that the outer planets of the TRAPPIST-1 system are capable of retaining their atmospheres over billion-year timescales. The consequences arising from our results are also explored in the context of abiogenesis, biodiversity, and searches for future exoplanets. In light of the many unknowns and assumptions involved, we recommend that these conclusions must be interpreted with due caution.}, } @article {pmid29284745, year = {2018}, author = {Baardink, G and Souslov, A and Paulose, J and Vitelli, V}, title = {Localizing softness and stress along loops in 3D topological metamaterials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {489-494}, pmid = {29284745}, issn = {1091-6490}, abstract = {Topological states can be used to control the mechanical properties of a material along an edge or around a localized defect. The rigidity of elastic networks is characterized by a topological invariant called the polarization; materials with a well-defined uniform polarization display a dramatic range of edge softness depending on the orientation of the polarization relative to the terminating surface. However, in all 3D mechanical metamaterials proposed to date, the topological modes are mixed with bulk soft modes, which organize themselves in Weyl loops. Here, we report the design of a 3D topological metamaterial without Weyl lines and with a uniform polarization that leads to an asymmetry between the number of soft modes on opposing surfaces. We then use this construction to localize topological soft modes in interior regions of the material by including defect lines-dislocation loops-that are unique to three dimensions. We derive a general formula that relates the difference in the number of soft modes and states of self-stress localized along the dislocation loop to the handedness of the vector triad formed by the lattice polarization, Burgers vector, and dislocation-line direction. Our findings suggest a strategy for preprogramming failure and softness localized along lines in 3D, while avoiding extended soft Weyl modes.}, } @article {pmid29284187, year = {2018}, author = {Cavoto, E and Neuenschwander, S and Goudet, J and Perrin, N}, title = {Sex-antagonistic genes, XY recombination and feminized Y chromosomes.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {416-427}, doi = {10.1111/jeb.13235}, pmid = {29284187}, issn = {1420-9101}, abstract = {The canonical model of sex-chromosome evolution predicts that sex-antagonistic (SA) genes play an instrumental role in the arrest of XY recombination and ensuing Y chromosome degeneration. Although this model might account for the highly differentiated sex chromosomes of birds and mammals, it does not fit the situation of many lineages of fish, amphibians or nonavian reptiles, where sex chromosomes are maintained homomorphic through occasional XY recombination and/or high turnover rates. Such situations call for alternative explanatory frameworks. A crucial issue at stake is the effect of XY recombination on the dynamics of SA genes and deleterious mutations. Using individual-based simulations, we show that a complete arrest of XY recombination actually benefits females, not males. Male fitness is maximized at different XY recombination rates depending on SA selection, but never at zero XY recombination. This should consistently favour some level of XY recombination, which in turn generates a recombination load at sex-linked SA genes. Hill-Robertson interferences with deleterious mutations also impede the differentiation of sex-linked SA genes, to the point that males may actually fix feminized phenotypes when SA selection and XY recombination are low. We argue that sex chromosomes might not be a good localization for SA genes, and sex conflicts seem better solved through the differential expression of autosomal genes.}, } @article {pmid29284184, year = {2018}, author = {Lockwood, BL and Gupta, T and Scavotto, R}, title = {Disparate patterns of thermal adaptation between life stages in temperate vs. tropical Drosophila melanogaster.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {323-331}, doi = {10.1111/jeb.13234}, pmid = {29284184}, issn = {1420-9101}, abstract = {Many terrestrial ectothermic species exhibit limited variation in upper thermal tolerance across latitude. However, these trends may not signify limited adaptive capacity to increase thermal tolerance in the face of climate change. Instead, thermal tolerance may be similar among populations because behavioural thermoregulation by mobile organisms or life stages may buffer natural selection for thermal tolerance. We compared thermal tolerance of adults and embryos among natural populations of Drosophila melanogaster from a broad range of thermal habitats around the globe to assess natural variation of thermal tolerance in mobile vs. immobile life stages. We found no variation among populations in adult thermal tolerance, but embryonic thermal tolerance was higher in tropical strains than in temperate strains. We further report that embryos live closer to their upper thermal limits than adults - that is, thermal safety margins are smaller for embryos than adults. F1 hybrid embryos from crosses between temperate and tropical populations had thermal tolerance that matched that of tropical embryos, suggesting the dominance of heat-tolerant alleles. Together, our findings suggest that thermal selection has led to divergence in embryonic thermal tolerance but that selection for divergent thermal tolerance may be limited in adults. Further, our results suggest that thermal traits should be measured across life stages to better predict adaptive limits.}, } @article {pmid29282842, year = {2018}, author = {Shi-Kunne, X and Faino, L and van den Berg, GCM and Thomma, BPHJ and Seidl, MF}, title = {Evolution within the fungal genus Verticillium is characterized by chromosomal rearrangement and gene loss.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1362-1373}, doi = {10.1111/1462-2920.14037}, pmid = {29282842}, issn = {1462-2920}, abstract = {The fungal genus Verticillium contains ten species, some of which are notorious plant pathogens causing vascular wilt diseases in host plants, while others are known as saprophytes and opportunistic plant pathogens. Whereas the genome of V. dahliae, the most notorious plant pathogen of the genus, has been well characterized, evolution and speciation of other members of the genus received little attention thus far. Here, we sequenced the genomes of the nine haploid Verticillium spp. to study evolutionary trajectories of their divergence from a last common ancestor. Frequent occurrence of chromosomal rearrangement and gene family loss was identified. In addition to ∼11 000 genes that are shared at least between two species, only 200-600 species-specific genes occur. Intriguingly, these species-specific genes show different features than the shared genes.}, } @article {pmid29282838, year = {2018}, author = {Chakraborty, A}, title = {The inositol pyrophosphate pathway in health and diseases.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1203-1227}, doi = {10.1111/brv.12392}, pmid = {29282838}, issn = {1469-185X}, support = {R01 DK103746/DK/NIDDK NIH HHS/United States ; }, abstract = {Inositol pyrophosphates (IPPs) are present in organisms ranging from plants, slime moulds and fungi to mammals. Distinct classes of kinases generate different forms of energetic diphosphate-containing IPPs from inositol phosphates (IPs). Conversely, polyphosphate phosphohydrolase enzymes dephosphorylate IPPs to regenerate the respective IPs. IPPs and/or their metabolizing enzymes regulate various cell biological processes by modulating many proteins via diverse mechanisms. In the last decade, extensive research has been conducted in mammalian systems, particularly in knockout mouse models of relevant enzymes. Results obtained from these studies suggest impacts of the IPP pathway on organ development, especially of brain and testis. Conversely, deletion of specific enzymes in the pathway protects mice from various diseases such as diet-induced obesity (DIO), type-2 diabetes (T2D), fatty liver, bacterial infection, thromboembolism, cancer metastasis and aging. Furthermore, pharmacological inhibition of the same class of enzymes in mice validates the therapeutic importance of this pathway in cardio-metabolic diseases. This review critically analyses these findings and summarizes the significance of the IPP pathway in mammalian health and diseases. It also evaluates benefits and risks of targeting this pathway in disease therapies. Finally, future directions of mammalian IPP research are discussed.}, } @article {pmid29282837, year = {2018}, author = {Bythell, JC and Brown, BE and Kirkwood, TBL}, title = {Do reef corals age?.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1192-1202}, doi = {10.1111/brv.12391}, pmid = {29282837}, issn = {1469-185X}, abstract = {Hydra is emerging as a model organism for studies of ageing in early metazoan animals, but reef corals offer an equally ancient evolutionary perspective as well as several advantages, not least being the hard exoskeleton which provides a rich fossil record as well as a record of growth and means of ageing of individual coral polyps. Reef corals are also widely regarded as potentially immortal at the level of the asexual lineage and are assumed not to undergo an intrinsic ageing process. However, putative molecular indicators of ageing have recently been detected in reef corals. While many of the large massive coral species attain considerable ages (>600 years) there are other much shorter-lived species where older members of some populations show catastrophic mortality, compared to juveniles, under environmental stress. Other studies suggestive of ageing include those demonstrating decreased reproduction, increased susceptibility to oxidative stress and disease, reduced regeneration potential and declining growth rate in mature colonies. This review aims to promote interest and research in reef coral ageing, both as a useful model for the early evolution of ageing and as a factor in studies of ecological impacts on reef systems in light of the enhanced effects of environmental stress on ageing in other organisms.}, } @article {pmid29282821, year = {2018}, author = {Durkin, ES and Luong, LT}, title = {Experimental evolution of infectious behaviour in a facultative ectoparasite.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {362-370}, doi = {10.1111/jeb.13227}, pmid = {29282821}, issn = {1420-9101}, abstract = {Parasitic lifestyles have evolved many times in animals, but how such life-history strategies evolved from free-living ancestors remains a great puzzle. Transitional symbiotic strategies, such as facultative parasitism, are hypothesized evolutionary stepping stones towards obligate parasitism. However, to consider this hypothesis, heritable genetic variation in infectious behaviour of transitional symbiotic strategies must exist. In this study, we experimentally evolved infectivity and estimated the additive genetic variation in a facultative parasite. We performed artificial selection experiments in which we selected for either increased or decreased propensity to infect in a facultatively parasitic mite (Macrocheles muscaedomesticae). Here, infectiousness was expressed in terms of mite attachment to a host (Drosophila hydei) and modelled as a threshold trait. Mites responded positively to selection for increased infectivity; realized heritability of infectious behaviour was significantly different from zero and estimated to be 16.6% (±4.4% SE). Further, infection prevalence was monitored for 20 generations post-selection. Selected lines continued to display relatively high levels of infection, demonstrating a degree of genetic stability in infectiousness. Our study is the first to provide an estimate of heritability and additive genetic variation for infectious behaviour in a facultative parasite, which suggests natural selection can act upon facultative strategies with important implications for the evolution of parasitism.}, } @article {pmid29282789, year = {2018}, author = {de Vries, LJ and van Langevelde, F}, title = {Two different strategies of host manipulation allow parasites to persist in intermediate-definitive host systems.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {393-404}, doi = {10.1111/jeb.13230}, pmid = {29282789}, issn = {1420-9101}, abstract = {Trophically transmitted parasites start their development in an intermediate host, before they finish the development in their definitive host when the definitive host preys on the intermediate host. In intermediate-definitive host systems, two strategies of host manipulation have been evolved: increasing the rate of transmission to the definitive host by increasing the chance that the definitive host will prey on the intermediate host, or increasing the lifespan of the parasite in the intermediate host by decreasing the predation chance when the intermediate host is not yet infectious. As the second strategy is less well studied than the first, it is unknown under what conditions each of these strategies is prevailed and evolved. We analysed the effect of both strategies on the presence of parasites in intermediate-definitive host systems with a structured population model. We show that the parasite can increase the parameter space where it can persist in the intermediate-definitive host system using one of these two strategies of host manipulation. We found that when the intermediate host or the definitive host has life-history traits that allow the definitive host to reach large population densities, that is high reproduction rate of the intermediate host or high conversion efficiency of the definitive host (efficiency at which the uninfected definitive host converts caught intermediate hosts into offspring), respectively, evolving manipulation to decrease the predation chance of the intermediate host will be more beneficial than manipulation to increase the predation chance to enhance transmission. Furthermore, manipulation to decrease the predation chance of the intermediate host results in higher population densities of infected intermediate hosts than manipulation that increases the predation chance to enhance transmission. Our study shows that host manipulation in early stages of the parasite development to decrease predation might be a more frequently evolved way of host manipulation than is currently assumed.}, } @article {pmid29282784, year = {2018}, author = {Saxon, AD and O'Brien, EK and Bridle, JR}, title = {Temperature fluctuations during development reduce male fitness and may limit adaptive potential in tropical rainforest Drosophila.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {405-415}, doi = {10.1111/jeb.13231}, pmid = {29282784}, issn = {1420-9101}, abstract = {Understanding the potential for organisms to tolerate thermal stress through physiological or evolutionary responses is crucial given rapid climate change. Although climate models predict increases in both temperature mean and variance, such tolerances are typically assessed under constant conditions. We tested the effects of temperature variability during development on male fitness in the rainforest fly Drosophila birchii, by simulating thermal variation typical of the warm and cool margins of its elevational distribution, and estimated heritabilities and genetic correlations of fitness traits. Reproductive success was reduced for males reared in warm (mean 24 °C) fluctuating (±3 °C) vs. constant conditions but not in cool fluctuating conditions (mean 17 °C), although fluctuations reduced body size at both temperatures. Male reproductive success under warm fluctuating conditions was similar to that at constant 27 °C, indicating that briefly exceeding critical thermal limits has similar fitness costs to continuously stressful conditions. There was substantial heritable variation in all traits. However, reproductive success traits showed no genetic correlation between treatments reflecting temperature variation at elevational extremes, which may constrain evolutionary responses at these ecological margins. Our data suggest that even small increases in temperature variability will threaten tropical ectotherms living close to their upper thermal limits, both through direct effects on fitness and by limiting their adaptive potential.}, } @article {pmid29282504, year = {2018}, author = {Le, TS and Southgate, PC and O'Connor, W and Poole, S and Kurtbӧke, DI}, title = {Bacteriophages as Biological Control Agents of Enteric Bacteria Contaminating Edible Oysters.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {611-619}, pmid = {29282504}, issn = {1432-0991}, mesh = {Animals ; Bacteriophages/genetics/isolation & purification/*physiology ; Biological Control Agents/isolation & purification/pharmacology ; Escherichia coli/growth & development/virology ; Food Contamination/analysis/*prevention & control ; Ostreidae/*microbiology ; Salmonella enterica/growth & development/virology ; Sewage/virology ; Shellfish/*microbiology ; }, abstract = {Bacterial contamination on seafood resulting from unhygienic food-handling practices causes foodborne diseases and significant revenue losses. Moreover, control measures are complicated by a high prevalence of antibiotic-resistant bacteria. Alternative measures such as the phage therapy, therefore, is considered as an environmental and consumer-friendly biological control strategy for controlling such bacterial contamination. In this study, we determined the effectiveness of a bacteriophage cocktail in controlling E. coli strains [JM 109, ATCC 13706 and the, extended spectrum beta-lactamase resistant strain (ATCC BAA 196)] and S. enterica subsp. enterica (ATCC 13311) as single and combined contaminants of the edible oysters. Five different E. coli-specific phages (belonging to the Siphoviridae family) and a Salmonella phage (belonging to the Tectiviridae family) were successfully isolated from sewage water samples taken from a local sewage treatment plan in the Sunshine Coast region of Australia. Phage treatments applied to the pathogens when they were presented on the oysters as either single or combined hosts, resulted in significant decrease of the number of these bacteria on edible oysters. Results obtained indicated that bacteriophages could have beneficial applications in oyster-processing plants in controlling pathogenic bacterial infestations. This study thus contributes towards ongoing international efforts into the effective use of bacteriophages for biological control purposes.}, } @article {pmid29282325, year = {2018}, author = {Porras, AM and Westlund, JA and Evans, AD and Masters, KS}, title = {Creation of disease-inspired biomaterial environments to mimic pathological events in early calcific aortic valve disease.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E363-E371}, pmid = {29282325}, issn = {1091-6490}, support = {R01 HL093281/HL/NHLBI NIH HHS/United States ; R21 EB019508/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Aortic Valve/*cytology/metabolism/*pathology ; Aortic Valve Stenosis/*pathology ; Biocompatible Materials ; Calcinosis/*pathology ; *Cell Culture Techniques ; Cells, Cultured ; Cholesterol, LDL ; Culture Media ; Cytokines/genetics/metabolism ; Gelatin ; Gene Expression Regulation/drug effects ; Glycosaminoglycans/pharmacology ; Hydrogels ; Lipoproteins, LDL ; Swine ; Tissue Culture Techniques ; }, abstract = {An insufficient understanding of calcific aortic valve disease (CAVD) pathogenesis remains a major obstacle in developing treatment strategies for this disease. The aim of the present study was to create engineered environments that mimic the earliest known features of CAVD and apply this in vitro platform to decipher relationships relevant to early valve lesion pathobiology. Glycosaminoglycan (GAG) enrichment is a dominant hallmark of early CAVD, but culture of valvular interstitial cells (VICs) in biomaterial environments containing pathological amounts of hyaluronic acid (HA) or chondroitin sulfate (CS) did not directly increase indicators of disease progression such as VIC activation or inflammatory cytokine production. However, HA-enriched matrices increased production of vascular endothelial growth factor (VEGF), while matrices displaying pathological levels of CS were effective at retaining lipoproteins, whose deposition is also found in early CAVD. Retained oxidized low-density lipoprotein (oxLDL), in turn, stimulated myofibroblastic VIC differentiation and secretion of numerous inflammatory cytokines. OxLDL also increased VIC deposition of GAGs, thereby creating a positive feedback loop to further enrich GAG content and promote disease progression. Using this disease-inspired in vitro platform, we were able to model a complex, multistep pathological sequence, with our findings suggesting distinct roles for individual GAGs in outcomes related to valve lesion progression, as well as key differences in cell-lipoprotein interactions compared with atherosclerosis. We propose a pathogenesis cascade that may be relevant to understanding early CAVD and envision the extension of such models to investigate other tissue pathologies or test pharmacological treatments.}, } @article {pmid29282324, year = {2018}, author = {Donnelly, CR and Shah, AA and Mistretta, CM and Bradley, RM and Pierchala, BA}, title = {Biphasic functions for the GDNF-Ret signaling pathway in chemosensory neuron development and diversification.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E516-E525}, pmid = {29282324}, issn = {1091-6490}, support = {R01 DC014428/DC/NIDCD NIH HHS/United States ; R01 DC015799/DC/NIDCD NIH HHS/United States ; R01 NS089585/NS/NINDS NIH HHS/United States ; F30 DE023479/DE/NIDCR NIH HHS/United States ; T32 DE007057/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*physiology ; Chemoreceptor Cells/*physiology ; Gene Expression Regulation, Developmental/*drug effects ; Geniculate Ganglion ; Glial Cell Line-Derived Neurotrophic Factor/genetics/*metabolism ; Homeodomain Proteins/genetics/metabolism ; Membrane Glycoproteins/genetics/metabolism ; Mice ; Mice, Knockout ; Protein-Tyrosine Kinases/genetics/metabolism ; Proto-Oncogene Proteins c-ret/genetics/*metabolism ; Pyrazoles/pharmacology ; Pyrimidines/pharmacology ; RNA, Untranslated/genetics/metabolism ; Signal Transduction ; Tamoxifen ; Taste/*physiology ; Temperature ; Tongue/innervation ; Touch ; Transcription Factor Brn-3A ; Transcription Factors/genetics/metabolism ; }, abstract = {The development of the taste system relies on the coordinated regulation of cues that direct the simultaneous development of both peripheral taste organs and innervating sensory ganglia, but the underlying mechanisms remain poorly understood. In this study, we describe a novel, biphasic function for glial cell line-derived neurotrophic factor (GDNF) in the development and subsequent diversification of chemosensory neurons within the geniculate ganglion (GG). GDNF, acting through the receptor tyrosine kinase Ret, regulates the expression of the chemosensory fate determinant Phox2b early in GG development. Ret-/- mice, but not Retfx/fx ; Phox2b-Cre mice, display a profound loss of Phox2b expression with subsequent chemosensory innervation deficits, indicating that Ret is required for the initial amplification of Phox2b expression but not its maintenance. Ret expression is extinguished perinatally but reemerges postnatally in a subpopulation of large-diameter GG neurons expressing the mechanoreceptor marker NF200 and the GDNF coreceptor GFRα1. Intriguingly, we observed that ablation of these neurons in adult Ret-Cre/ERT2; Rosa26LSL-DTA mice caused a specific loss of tactile, but not chemical or thermal, electrophysiological responses. Overall, the GDNF-Ret pathway exerts two critical and distinct functions in the peripheral taste system: embryonic chemosensory cell fate determination and the specification of lingual mechanoreceptors.}, } @article {pmid29282323, year = {2018}, author = {Peled, M and Tocheva, AS and Sandigursky, S and Nayak, S and Philips, EA and Nichols, KE and Strazza, M and Azoulay-Alfaguter, I and Askenazi, M and Neel, BG and Pelzek, AJ and Ueberheide, B and Mor, A}, title = {Affinity purification mass spectrometry analysis of PD-1 uncovers SAP as a new checkpoint inhibitor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E468-E477}, pmid = {29282323}, issn = {1091-6490}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; R01 AI125640/AI/NIAID NIH HHS/United States ; R01 CA049152/CA/NCI NIH HHS/United States ; T32 AI100853/AI/NIAID NIH HHS/United States ; T32 AR069515/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Biomarkers, Tumor ; Cell Cycle Checkpoints/*physiology ; Cell Proliferation/physiology ; Cytokines/genetics/metabolism ; Gene Expression Regulation, Enzymologic ; Gene Silencing ; HEK293 Cells ; Humans ; Jurkat Cells ; Male ; Mass Spectrometry/*methods ; Mice ; Mice, Knockout ; Programmed Cell Death 1 Receptor/genetics/*metabolism ; Protein Tyrosine Phosphatase, Non-Receptor Type 11/genetics/metabolism ; Signaling Lymphocytic Activation Molecule Family/genetics/*metabolism ; T-Lymphocytes/*metabolism ; }, abstract = {Programmed cell death-1 (PD-1) is an essential inhibitory receptor in T cells. Antibodies targeting PD-1 elicit durable clinical responses in patients with multiple tumor indications. Nevertheless, a significant proportion of patients do not respond to anti-PD-1 treatment, and a better understanding of the signaling pathways downstream of PD-1 could provide biomarkers for those whose tumors respond and new therapeutic approaches for those whose tumors do not. We used affinity purification mass spectrometry to uncover multiple proteins associated with PD-1. Among these proteins, signaling lymphocytic activation molecule-associated protein (SAP) was functionally and mechanistically analyzed for its contribution to PD-1 inhibitory responses. Silencing of SAP augmented and overexpression blocked PD-1 function. T cells from patients with X-linked lymphoproliferative disease (XLP), who lack functional SAP, were hyperresponsive to PD-1 signaling, confirming its inhibitory role downstream of PD-1. Strikingly, signaling downstream of PD-1 in purified T cell subsets did not correlate with PD-1 surface expression but was inversely correlated with intracellular SAP levels. Mechanistically, SAP opposed PD-1 function by acting as a molecular shield of key tyrosine residues that are targets for the tyrosine phosphatase SHP2, which mediates PD-1 inhibitory properties. Our results identify SAP as an inhibitor of PD-1 function and SHP2 as a potential therapeutic target in patients with XLP.}, } @article {pmid29282322, year = {2018}, author = {Martínez-Velázquez, LA and Ringstad, N}, title = {Antagonistic regulation of trafficking to Caenorhabditis elegans sensory cilia by a Retinal Degeneration 3 homolog and retromer.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E438-E447}, pmid = {29282322}, issn = {1091-6490}, support = {T32 NS086750/NS/NINDS NIH HHS/United States ; P40 OD010440/OD/NIH HHS/United States ; F31 EY024836/EY/NEI NIH HHS/United States ; R35 GM122573/GM/NIGMS NIH HHS/United States ; T32 GM007308/GM/NIGMS NIH HHS/United States ; R01 GM113182/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans/*physiology ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cilia/*physiology ; Eye Proteins/classification/genetics/*metabolism ; Gene Expression Regulation ; Protein Transport/*physiology ; Sensory Receptor Cells/physiology ; }, abstract = {Sensory neurons often possess cilia with elaborate membrane structures that are adapted to the sensory modality of the host cell. Mechanisms that target sensory transduction proteins to these specialized membrane domains remain poorly understood. Here, we show that a homolog of the human retinal dystrophy gene Retinal Degeneration 3 (RD3) is a Golgi-associated protein required for efficient trafficking of a sensory receptor, the receptor-type guanylate cyclase GCY-9, to cilia in chemosensory neurons of the nematode Caenorhabditis elegans The trafficking defect caused by mutation of the nematode RD3 homolog is suppressed in vivo by mutation of key components of the retromer complex, which mediates recycling of cargo from endosomes to the Golgi. Our data show that there exists a critical balance in sensory neurons between the rates of anterograde and retrograde trafficking of cargo destined for the sensory cilium and this balance requires molecular specialization at an early stage of the secretory pathway.}, } @article {pmid29282321, year = {2018}, author = {Carrette, LLG and Wang, CY and Wei, C and Press, W and Ma, W and Kelleher, RJ and Lee, JT}, title = {A mixed modality approach towards Xi reactivation for Rett syndrome and other X-linked disorders.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E668-E675}, pmid = {29282321}, issn = {1091-6490}, support = {R01 DA036895/DA/NIDA NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Azacitidine/*analogs & derivatives/pharmacology/therapeutic use ; Brain/metabolism ; Cell Line ; DNA Methylation/drug effects ; Decitabine ; Female ; Gene Expression Profiling ; Genetic Therapy/*methods ; Male ; Methyl-CpG-Binding Protein 2/*genetics ; Mice ; Oligonucleotides, Antisense/*therapeutic use ; Rett Syndrome/genetics/*therapy ; X Chromosome Inactivation ; }, abstract = {The X-chromosome harbors hundreds of disease genes whose associated diseases predominantly affect males. However, a subset, including neurodevelopmental disorders, Rett syndrome (RTT), fragile X syndrome, and CDKL5 syndrome, also affects females. These disorders lack disease-specific treatment. Because female cells carry two X chromosomes, an emerging treatment strategy has been to reawaken the healthy allele on the inactive X (Xi). Here, we focus on methyl-CpG binding protein 2 (MECP2) restoration for RTT and combinatorially target factors in the interactome of Xist, the noncoding RNA responsible for X inactivation. We identify a mixed modality approach combining an Xist antisense oligonucleotide and a small-molecule inhibitor of DNA methylation, which, together, achieve 30,000-fold MECP2 up-regulation from the Xi in cultured cells. Combining a brain-specific genetic Xist ablation with short-term 5-aza-2'-deoxycytidine (Aza) treatment models the synergy in vivo without evident toxicity. The Xi is selectively reactivated. These experiments provide proof of concept for a mixed modality approach for treating X-linked disorders in females.}, } @article {pmid29282320, year = {2018}, author = {Ding, Z and Huang, Y and Bailey, SK and Gao, Y and Cutting, LE and Rogers, BP and Newton, AT and Gore, JC}, title = {Detection of synchronous brain activity in white matter tracts at rest and under functional loading.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {595-600}, pmid = {29282320}, issn = {1091-6490}, support = {R01 HD067254/HD/NICHD NIH HHS/United States ; U54 HD083211/HD/NICHD NIH HHS/United States ; R01 HD044073/HD/NICHD NIH HHS/United States ; R01 NS093669/NS/NINDS NIH HHS/United States ; F31 HD090923/HD/NICHD NIH HHS/United States ; }, mesh = {Adult ; Female ; Gray Matter/chemistry/diagnostic imaging/physiology ; Humans ; Magnetic Resonance Imaging ; Male ; Oxygen/metabolism ; Rest ; White Matter/chemistry/diagnostic imaging/*physiology ; Young Adult ; }, abstract = {Functional MRI based on blood oxygenation level-dependent (BOLD) contrast is well established as a neuroimaging technique for detecting neural activity in the cortex of the human brain. While detection and characterization of BOLD signals, as well as their electrophysiological and hemodynamic/metabolic origins, have been extensively studied in gray matter (GM), the detection and interpretation of BOLD signals in white matter (WM) remain controversial. We have previously observed that BOLD signals in a resting state reveal structure-specific anisotropic temporal correlations in WM and that external stimuli alter these correlations and permit visualization of task-specific fiber pathways, suggesting variations in WM BOLD signals are related to neural activity. In this study, we provide further strong evidence that BOLD signals in WM reflect neural activities both in a resting state and under functional loading. We demonstrate that BOLD signal waveforms in stimulus-relevant WM pathways are synchronous with the applied stimuli but with various degrees of time delay and that signals in WM pathways exhibit clear task specificity. Furthermore, resting-state signal fluctuations in WM tracts show significant correlations with specific parcellated GM volumes. These observations support the notion that neural activities are encoded in WM circuits similarly to cortical responses.}, } @article {pmid29282319, year = {2018}, author = {Zhao, X and Deng, P and Iglesias-Bartolome, R and Amornphimoltham, P and Steffen, DJ and Jin, Y and Molinolo, AA and de Castro, LF and Ovejero, D and Yuan, Q and Chen, Q and Han, X and Bai, D and Taylor, SS and Yang, Y and Collins, MT and Gutkind, JS}, title = {Expression of an active Gαs mutant in skeletal stem cells is sufficient and necessary for fibrous dysplasia initiation and maintenance.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E428-E437}, pmid = {29282319}, issn = {1091-6490}, support = {R01 DE025866/DE/NIDCR NIH HHS/United States ; T32 GM007752/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/toxicity ; Bone Development/drug effects ; Bone and Bones/pathology ; Cell Differentiation ; Doxycycline/toxicity ; Fibrous Dysplasia of Bone/*metabolism ; GTP-Binding Protein alpha Subunits, Gs/genetics/*metabolism ; Gene Expression Regulation ; Gene Expression Regulation, Developmental/drug effects ; Mesenchymal Stem Cells/*metabolism ; Mice ; Mutation ; }, abstract = {Fibrous dysplasia (FD) is a disease caused by postzygotic activating mutations of GNAS (R201C and R201H) that encode the α-subunit of the Gs stimulatory protein. FD is characterized by the development of areas of abnormal fibroosseous tissue in the bones, resulting in skeletal deformities, fractures, and pain. Despite the well-defined genetic alterations underlying FD, whether GNAS activation is sufficient for FD initiation and the molecular and cellular consequences of GNAS mutations remains largely unresolved, and there are no currently available targeted therapeutic options for FD. Here, we have developed a conditional tetracycline (Tet)-inducible animal model expressing the GαsR201C in the skeletal stem cell (SSC) lineage (Tet-GαsR201C/Prrx1-Cre/LSL-rtTA-IRES-GFP mice), which develops typical FD bone lesions in both embryos and adult mice in less than 2 weeks following doxycycline (Dox) administration. Conditional GαsR201C expression promoted PKA activation and proliferation of SSCs along the osteogenic lineage but halted their differentiation to mature osteoblasts. Rather, as is seen clinically, areas of woven bone admixed with fibrous tissue were formed. GαsR201C caused the concomitant expression of receptor activator of nuclear factor kappa-B ligand (Rankl) that led to marked osteoclastogenesis and bone resorption. GαsR201C expression ablation by Dox withdrawal resulted in FD-like lesion regression, supporting the rationale for Gαs-targeted drugs to attempt FD cure. This model, which develops FD-like lesions that can form rapidly and revert on cessation of mutant Gαs expression, provides an opportunity to identify the molecular mechanism underlying FD initiation and progression and accelerate the development of new treatment options.}, } @article {pmid29282318, year = {2018}, author = {Sen, S and Wang, F and Zhang, J and He, Z and Ma, J and Gwack, Y and Xu, J and Sun, Z}, title = {SRC1 promotes Th17 differentiation by overriding Foxp3 suppression to stimulate RORγt activity in a PKC-θ-dependent manner.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E458-E467}, pmid = {29282318}, issn = {1091-6490}, support = {P30 CA033572/CA/NCI NIH HHS/United States ; R01 AI053147/AI/NIAID NIH HHS/United States ; R01 AI083432/AI/NIAID NIH HHS/United States ; R01 AI109644/AI/NIAID NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Cell Differentiation/*physiology ; Forkhead Transcription Factors/genetics/*metabolism ; Gene Deletion ; Gene Expression Regulation, Enzymologic/physiology ; Interleukins/genetics/metabolism ; Mice ; Nuclear Receptor Coactivator 1/chemistry/genetics/*metabolism ; Nuclear Receptor Subfamily 1, Group F, Member 3/genetics/*metabolism ; Protein Kinase C-theta/genetics/*metabolism ; Th17 Cells/*physiology ; }, abstract = {Th17 cells are major players in multiple autoimmune diseases and are developmentally contingent on reciprocal functionality between the transcription factor Retineic acid receptor-related orphan nuclear receptor gamma (RORγt) and Forkhead box protein P3 (Foxp3). Here we deciphered a previously unappreciated role of Steroid receptor coactivator 1 (SRC1) in defining the lineage decision for the development of Th17 versus induced T-regulatory (iTreg) cells. We demonstrate that SRC1 functions as a critical coactivator for RORγt in vivo to promote the functional dominance of RORγt over Foxp3 and thus establishing an unopposed Th17 differentiation program. In the absence of SRC1, T cell polarization resulted in decreased IL-17+ and increased Foxp3+ cells during both in vitro differentiation and in vivo development of experimental autoimmune encephalomyelitis. Mechanistically, T cell receptor (TCR) signaling molecule protein kinase C theta (PKC-θ)-mediated phosphorylation of SRC1 is important for inducing enhanced RORγt-SRC1 interaction, stable DNA binding, and resultant IL-17A transcription. Furthermore, phospho-SRC1-mediated recruitment of CARM1 induced prominent asymmetric dimethylation of H3R17 while preventing repressive H3K9 trimethylation and hence further modifying the IL-17 locus for optimal transcription. Moreover, binding of phospho-SRC1 to RORγt displaced bound Foxp3, leading to prompt degradation of the dissociated Foxp3 via a ubiquitin-proteosomal pathway and hence reversing the inhibitory action of Foxp3 on RORγt activity. Thus, SRC1 acts as a crucial molecular mediator to integrate positive PKC-θ-dependent TCR signals to induce peak RORγt activity and establish phenotypic dominance of Th17 over the iTreg pathway.}, } @article {pmid29282317, year = {2018}, author = {Piasecka, B and Duffy, D and Urrutia, A and Quach, H and Patin, E and Posseme, C and Bergstedt, J and Charbit, B and Rouilly, V and MacPherson, CR and Hasan, M and Albaud, B and Gentien, D and Fellay, J and Albert, ML and Quintana-Murci, L and , }, title = {Distinctive roles of age, sex, and genetics in shaping transcriptional variation of human immune responses to microbial challenges.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E488-E497}, pmid = {29282317}, issn = {1091-6490}, mesh = {Adult ; Aged ; *Aging ; Bacteria/immunology ; Cohort Studies ; Enterotoxins/immunology ; Female ; Fungi/immunology ; Gene Expression Regulation/*immunology ; *Genetic Variation ; Genotype ; Humans ; Influenza A virus/immunology ; Male ; Middle Aged ; Quantitative Trait Loci ; Young Adult ; }, abstract = {The contribution of host genetic and nongenetic factors to immunological differences in humans remains largely undefined. Here, we generated bacterial-, fungal-, and viral-induced immune transcriptional profiles in an age- and sex-balanced cohort of 1,000 healthy individuals and searched for the determinants of immune response variation. We found that age and sex affected the transcriptional response of most immune-related genes, with age effects being more stimulus-specific relative to sex effects, which were largely shared across conditions. Although specific cell populations mediated the effects of age and sex on gene expression, including CD8+ T cells for age and CD4+ T cells and monocytes for sex, we detected a direct effect of these intrinsic factors for the majority of immune genes. The mapping of expression quantitative trait loci (eQTLs) revealed that genetic factors had a stronger effect on immune gene regulation than age and sex, yet they affected a smaller number of genes. Importantly, we identified numerous genetic variants that manifested their regulatory effects exclusively on immune stimulation, including a Candida albicans-specific master regulator at the CR1 locus. These response eQTLs were enriched in disease-associated variants, particularly for autoimmune and inflammatory disorders, indicating that differences in disease risk may result from regulatory variants exerting their effects only in the presence of immune stress. Together, this study quantifies the respective effects of age, sex, genetics, and cellular heterogeneity on the interindividual variability of immune responses and constitutes a valuable resource for further exploration in the context of different infection risks or disease outcomes.}, } @article {pmid29282316, year = {2018}, author = {Bhunia, BK and Kaplan, DL and Mandal, BB}, title = {Silk-based multilayered angle-ply annulus fibrosus construct to recapitulate form and function of the intervertebral disc.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {477-482}, pmid = {29282316}, issn = {1091-6490}, mesh = {Animals ; Annulus Fibrosus/chemistry/*cytology/metabolism ; Biomechanical Phenomena ; Cell Proliferation ; Cells, Cultured ; Collagen/metabolism ; Extracellular Matrix/metabolism ; Humans ; Intervertebral Disc/chemistry/*cytology/metabolism ; Mesenchymal Stem Cells/cytology/metabolism ; Silk/*chemistry ; Swine ; Tissue Engineering/*instrumentation ; Tissue Scaffolds/chemistry ; }, abstract = {Recapitulation of the form and function of complex tissue organization using appropriate biomaterials impacts success in tissue engineering endeavors. The annulus fibrosus (AF) represents a complex, multilamellar, hierarchical structure consisting of collagen, proteoglycans, and elastic fibers. To mimic the intricacy of AF anatomy, a silk protein-based multilayered, disc-like angle-ply construct was fabricated, consisting of concentric layers of lamellar sheets. Scanning electron microscopy and fluorescence image analysis revealed cross-aligned and lamellar characteristics of the construct, mimicking the native hierarchical architecture of the AF. Induction of secondary structure in the silk constructs was confirmed by infrared spectroscopy and X-ray diffraction. The constructs showed a compressive modulus of 499.18 ± 86.45 kPa. Constructs seeded with porcine AF cells and human mesenchymal stem cells (hMSCs) showed ∼2.2-fold and ∼1.7-fold increases in proliferation on day 14, respectively, compared with initial seeding. Biochemical analysis, histology, and immunohistochemistry results showed the deposition of AF-specific extracellular matrix (sulfated glycosaminoglycan and collagen type I), indicating a favorable environment for both cell types, which was further validated by the expression of AF tissue-specific genes. The constructs seeded with porcine AF cells showed ∼11-, ∼5.1-, and ∼6.7-fold increases in col Iα 1, sox 9, and aggrecan genes, respectively. The differentiation of hMSCs to AF-like tissue was evident from the enhanced expression of the AF-specific genes. Overall, the constructs supported cell proliferation, differentiation, and ECM deposition resulting in AF-like tissue features based on ECM deposition and morphology, indicating potential for future studies related to intervertebral disc replacement therapy.}, } @article {pmid29282315, year = {2018}, author = {Li, F and Yang, C and Yuan, F and Liao, D and Li, T and Guilak, F and Zhong, P}, title = {Dynamics and mechanisms of intracellular calcium waves elicited by tandem bubble-induced jetting flow.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E353-E362}, pmid = {29282315}, issn = {1091-6490}, support = {R01 AR048182/AR/NIAMS NIH HHS/United States ; R03 EB017886/EB/NIBIB NIH HHS/United States ; R37 DK052985/DK/NIDDK NIH HHS/United States ; S10 RR016802/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Calcium Signaling/*physiology ; Cell Membrane/*physiology ; HeLa Cells ; Humans ; Mechanotransduction, Cellular/*physiology ; Microfluidics ; Shear Strength ; }, abstract = {One of the earliest events in cellular mechanotransduction is often an increase in intracellular calcium concentration associated with intracellular calcium waves (ICWs) in various physiologic or pathophysiologic processes. Although cavitation-induced calcium responses are believed to be important for modulating downstream bioeffects such as cell injury and mechanotransduction in ultrasound therapy, the fundamental mechanisms of these responses have not been elucidated. In this study, we investigated mechanistically the ICWs elicited in single HeLa cells by the tandem bubble-induced jetting flow in a microfluidic system. We identified two distinct (fast and slow) types of ICWs at varying degrees of flow shear stress-induced membrane deformation, as determined by different bubble standoff distances. We showed that ICWs were initiated by an extracellular calcium influx across the cell membrane nearest to the jetting flow, either primarily through poration sites for fast ICWs or opening of mechanosensitive ion channels for slow ICWs, which then propagated in the cytosol via a reaction-diffusion process from the endoplasmic reticulum. The speed of ICW (CICW) was found to correlate strongly with the severity of cell injury, with CICW in the range of 33 μm/s to 93 μm/s for fast ICWs and 1.4 μm/s to 12 μm/s for slow ICWs. Finally, we demonstrated that micrometer-sized beads attached to the cell membrane integrin could trigger ICWs under mild cavitation conditions without collateral injury. The relation between the characteristics of ICW and cell injury, and potential strategies to mitigate cavitation-induced injury while evoking an intracellular calcium response, may be particularly useful for exploiting ultrasound-stimulated mechanotransduction applications in the future.}, } @article {pmid29282314, year = {2018}, author = {Tallavaara, M and Eronen, JT and Luoto, M}, title = {Productivity, biodiversity, and pathogens influence the global hunter-gatherer population density.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {6}, pages = {1232-1237}, pmid = {29282314}, issn = {1091-6490}, mesh = {Altitude ; Animals ; Australia ; *Biodiversity ; Birds ; Forests ; Host-Pathogen Interactions/*physiology ; Humans ; Mammals ; Models, Biological ; North America ; Plants ; *Population Density ; }, abstract = {The environmental drivers of species distributions and abundances are at the core of ecological research. However, the effects of these drivers on human abundance are not well-known. Here, we report how net primary productivity, biodiversity, and pathogen stress affect human population density using global ethnographic hunter-gatherer data. Our results show that productivity has significant effects on population density globally. The most important direct drivers, however, depend on environmental conditions: biodiversity influences population density exclusively in low-productivity regions, whereas pathogen stress does so in high-productivity regions. Our results also indicate that subtropical and temperate forest biomes provide the highest carrying capacity for hunter-gatherer populations. These findings document that environmental factors play a key role in shaping global population density patterns of preagricultural humans.}, } @article {pmid29281028, year = {2018}, author = {Gunišová, S and Hronová, V and Mohammad, MP and Hinnebusch, AG and Valášek, LS}, title = {Please do not recycle! Translation reinitiation in microbes and higher eukaryotes.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {2}, pages = {165-192}, pmid = {29281028}, issn = {1574-6976}, support = {090812/B/09/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Bacteria/*genetics/metabolism ; Eukaryota/*genetics ; Humans ; Open Reading Frames/genetics ; Protein Biosynthesis/genetics/*physiology ; }, abstract = {Protein production must be strictly controlled at its beginning and end to synthesize a polypeptide that faithfully copies genetic information carried in the encoding mRNA. In contrast to viruses and prokaryotes, the majority of mRNAs in eukaryotes contain only one coding sequence, resulting in production of a single protein. There are, however, many exceptional mRNAs that either carry short open reading frames upstream of the main coding sequence (uORFs) or even contain multiple long ORFs. A wide variety of mechanisms have evolved in microbes and higher eukaryotes to prevent recycling of some or all translational components upon termination of the first translated ORF in such mRNAs and thereby enable subsequent translation of the next uORF or downstream coding sequence. These specialized reinitiation mechanisms are often regulated to couple translation of the downstream ORF to various stimuli. Here we review all known instances of both short uORF-mediated and long ORF-mediated reinitiation and present our current understanding of the underlying molecular mechanisms of these intriguing modes of translational control.}, } @article {pmid29281015, year = {2018}, author = {Stritt, C and Gordon, SP and Wicker, T and Vogel, JP and Roulin, AC}, title = {Recent Activity in Expanding Populations and Purifying Selection Have Shaped Transposable Element Landscapes across Natural Accessions of the Mediterranean Grass Brachypodium distachyon.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {304-318}, pmid = {29281015}, issn = {1759-6653}, mesh = {Brachypodium/*genetics ; *DNA Transposable Elements ; DNA, Plant/*genetics ; Ecosystem ; Evolution, Molecular ; Gene Frequency ; Genetic Drift ; Genetic Variation ; Genome, Plant ; Mediterranean Region ; Phylogeny ; Polymorphism, Genetic ; *Selection, Genetic ; }, abstract = {Transposable element (TE) activity has emerged as a major cause of variation in genome size and structure among species. To what extent TEs contribute to genetic variation and divergence within species, however, is much less clear, mainly because population genomic data have so far only been available for the classical model organisms. In this study, we use the annual Mediterranean grass Brachypodium distachyon to investigate TE dynamics in natural populations. Using whole-genome sequencing data for 53 natural accessions, we identified more than 5,400 TE polymorphisms across the studied genomes. We found, first, that while population bottlenecks and expansions have shaped genetic diversity in B. distachyon, these events did not lead to lineage-specific activations of TE families, as observed in other species. Instead, the same families have been active across the species range and TE activity is homogeneous across populations, indicating the presence of conserved regulatory mechanisms. Second, almost half of the TE insertion polymorphisms are accession-specific, most likely because of recent activity in expanding populations and the action of purifying selection. And finally, although TE insertion polymorphisms are underrepresented in and around genes, more than 1,000 of them occur in genic regions and could thus contribute to functional divergence. Our study shows that while TEs in B. distachyon are "well-behaved" compared with TEs in other species with larger genomes, they are an abundant source of lineage-specific genetic variation and may play an important role in population divergence and adaptation.}, } @article {pmid29280478, year = {2018}, author = {Smith, SD and Kriebel, R}, title = {Convergent evolution of floral shape tied to pollinator shifts in Iochrominae (Solanaceae).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {688-697}, doi = {10.1111/evo.13416}, pmid = {29280478}, issn = {1558-5646}, abstract = {Flower form is one of many floral features thought to be shaped by pollinator-mediated selection. Although the drivers of variation in flower shape have often been examined in microevolutionary studies, relatively few have tested the relationship between shape evolution and shifts in pollination system across clades. In the present study, we use morphometric approaches to quantify shape variation across the Andean clade Iochrominae and estimate the relationship between changes in shape and shifts in pollination system using phylogenetic comparative methods. We infer multiple shifts from an ancestral state of narrow, tubular flowers toward open, bowl-shaped, or campanulate flowers as well as one reversal to the tubular form. These transitions in flower shape are significantly correlated with changes in pollination system. Specifically, tubular forms tend to be hummingbird-pollinated and the open forms tend to be insect-pollinated, a pattern consistent with experimental work as well as classical floral syndromes. Nonetheless, our study provides one of the few empirical demonstrations of the relationship between flower shape and pollination system at a macroevolutionary scale.}, } @article {pmid29280149, year = {2018}, author = {Adams, DC and Nason, JD}, title = {A phylogenetic comparative method for evaluating trait coevolution across two phylogenies for sets of interacting species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {234-243}, doi = {10.1111/evo.13415}, pmid = {29280149}, issn = {1558-5646}, abstract = {Evaluating trait correlations across species within a lineage via phylogenetic regression is fundamental to comparative evolutionary biology, but when traits of interest are derived from two sets of lineages that coevolve with one another, methods for evaluating such patterns in a dual-phylogenetic context remain underdeveloped. Here, we extend multivariate permutation-based phylogenetic regression to evaluate trait correlations in two sets of interacting species while accounting for their respective phylogenies. This extension is appropriate for both univariate and multivariate response data, and may use one or more independent variables, including environmental covariates. Imperfect correspondence between species in the interacting lineages can also be accommodated, such as when species in one lineage associate with multiple species in the other, or when there are unmatched taxa in one or both lineages. For both univariate and multivariate data, the method displays appropriate type I error, and statistical power increases with the strength of the trait covariation and the number of species in the phylogeny. These properties are retained even when there is not a 1:1 correspondence between lineages. Finally, we demonstrate the approach by evaluating the evolutionary correlation between traits in fig species and traits in their agaonid wasp pollinators. R computer code is provided.}, } @article {pmid29279978, year = {2018}, author = {Jiang, Y and Liu, J and Dong, W and Zhang, W and Fang, Y and Ma, J and Jiang, M and Xin, F}, title = {The Draft Genome Sequence of Thermophilic Thermoanaerobacterium thermosaccharolyticum M5 Capable of Directly Producing Butanol from Hemicellulose.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {620-623}, pmid = {29279978}, issn = {1432-0991}, support = {No. BK20170993//the Jiangsu Province Natural Science Foundation for Youths/ ; 21706125//the National Natural Science Foundation of China/ ; 21727818//the National Natural Science Foundation of China/ ; 21706124//the National Natural Science Foundation of China/ ; 31700092//the National Natural Science Foundation of China/ ; KL16-08//the Project of State Key Laboratory of Materials-Oriented Chemical Engineering/ ; }, mesh = {Archaeal Proteins/genetics ; Base Composition ; Butanols/*metabolism ; Ethanol ; *Genome, Archaeal ; Phylogeny ; Polysaccharides/*metabolism ; Thermoanaerobacterium/classification/*genetics/isolation & purification/metabolism ; }, abstract = {A novel thermophilic and butanogenic Thermoanaerobacterium thermosaccharolyticum M5 was successfully isolated and characterized, which could produce butanol from hemicellulose via a unique ethanol-butanol (EB) pathway through consolidated bioprocessing (CBP). This represents the first wild-type bacterium which could produce butanol from hemicellulose via CBP under thermophilic conditions. The assembled draft genome of strain M5 is 2.64 Mp, which contains 2638 genes and 2465 protein-coding sequences with 33.90% G + C content. Among these annotated proteins, xylanases, xylosidases, and bifunctional alcohol/aldehyde dehydrogenase (AdhE) play key roles in the achievement of EB production from hemicellulose through CBP.}, } @article {pmid29279607, year = {2018}, author = {Koch, L}, title = {Technique: Single-cell transcriptomes in space.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {64-65}, pmid = {29279607}, issn = {1471-0064}, } @article {pmid29279606, year = {2018}, author = {Dhiman, VK and Bolt, MJ and White, KP}, title = {Nuclear receptors in cancer - uncovering new and evolving roles through genomic analysis.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {160-174}, pmid = {29279606}, issn = {1471-0064}, abstract = {Nuclear receptors (NRs) have historically been at the forefront of cancer research, where they are known to act as critical regulators of disease. They also serve as biomarkers for tumour subclassification and targets for hormone therapy. However, most tumour types express extensive repertoires of NRs, whose interactions provide multiple paths for disease progression and offer potentially untapped mechanisms for therapeutic interventions. Recently, next-generation sequencing technologies have provided genome-wide insights into the complex interplay of NR transcriptional networks and their contribution to the development and progression of cancer. These findings have altered the traditional understanding of NR activities in oncogenesis.}, } @article {pmid29279605, year = {2018}, author = {Cieślik, M and Chinnaiyan, AM}, title = {Cancer transcriptome profiling at the juncture of clinical translation.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {93-109}, pmid = {29279605}, issn = {1471-0064}, abstract = {Methodological breakthroughs over the past four decades have repeatedly revolutionized transcriptome profiling. Using RNA sequencing (RNA-seq), it has now become possible to sequence and quantify the transcriptional outputs of individual cells or thousands of samples. These transcriptomes provide a link between cellular phenotypes and their molecular underpinnings, such as mutations. In the context of cancer, this link represents an opportunity to dissect the complexity and heterogeneity of tumours and to discover new biomarkers or therapeutic strategies. Here, we review the rationale, methodology and translational impact of transcriptome profiling in cancer.}, } @article {pmid29279411, year = {2018}, author = {Thompson, EH and Lensjø, KK and Wigestrand, MB and Malthe-Sørenssen, A and Hafting, T and Fyhn, M}, title = {Removal of perineuronal nets disrupts recall of a remote fear memory.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {607-612}, pmid = {29279411}, issn = {1091-6490}, mesh = {Animals ; Behavior, Animal ; *Fear ; Male ; *Memory ; Mental Recall ; Neuronal Plasticity ; Rats ; Rats, Sprague-Dawley ; Visual Cortex/chemistry/*physiology ; }, abstract = {Throughout life animals learn to recognize cues that signal danger and instantaneously initiate an adequate threat response. Memories of such associations may last a lifetime and far outlast the intracellular molecules currently found to be important for memory processing. The memory engram may be supported by other more stable molecular components, such as the extracellular matrix structure of perineuronal nets (PNNs). Here, we show that recall of remote, but not recent, visual fear memories in rats depend on intact PNNs in the secondary visual cortex (V2L). Supporting our behavioral findings, increased synchronized theta oscillations between V2L and basolateral amygdala, a physiological correlate of successful recall, was absent in rats with degraded PNNs in V2L. Together, our findings suggest a role for PNNs in remote memory processing by stabilizing the neural network of the engram.}, } @article {pmid29279410, year = {2018}, author = {Tang, C and Klukovich, R and Peng, H and Wang, Z and Yu, T and Zhang, Y and Zheng, H and Klungland, A and Yan, W}, title = {ALKBH5-dependent m6A demethylation controls splicing and stability of long 3'-UTR mRNAs in male germ cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E325-E333}, pmid = {29279410}, issn = {1091-6490}, support = {P30 GM110767/GM/NIGMS NIH HHS/United States ; R01 HD060858/HD/NICHD NIH HHS/United States ; R01 HD085506/HD/NICHD NIH HHS/United States ; R21 HD071736/HD/NICHD NIH HHS/United States ; }, mesh = {3' Untranslated Regions ; AlkB Homolog 5, RNA Demethylase/genetics/*metabolism ; Animals ; Demethylation ; Germ Cells ; Male ; Membrane Glycoproteins/genetics/*metabolism ; Mice ; Mice, Knockout ; Nerve Tissue Proteins/genetics/*metabolism ; RNA Splicing/*physiology ; RNA, Messenger/genetics/metabolism ; Spermatocytes/*physiology ; }, abstract = {N6-methyladenosine (m6A) represents one of the most common RNA modifications in eukaryotes. Specific m6A writer, eraser, and reader proteins have been identified. As an m6A eraser, ALKBH5 specifically removes m6A from target mRNAs and inactivation of Alkbh5 leads to male infertility in mice. However, the underlying molecular mechanism remains unknown. Here, we report that ALKBH5-mediated m6A erasure in the nuclei of spermatocytes and round spermatids is essential for correct splicing and the production of longer 3'-UTR mRNAs, and failure to do so leads to aberrant splicing and production of shorter transcripts with elevated levels of m6A that are rapidly degraded. Our study identified reversible m6A modification as a critical mechanism of posttranscriptional control of mRNA fate in late meiotic and haploid spermatogenic cells.}, } @article {pmid29279409, year = {2018}, author = {Mitchell, G and Cheng, MI and Chen, C and Nguyen, BN and Whiteley, AT and Kianian, S and Cox, JS and Green, DR and McDonald, KL and Portnoy, DA}, title = {Listeria monocytogenes triggers noncanonical autophagy upon phagocytosis, but avoids subsequent growth-restricting xenophagy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E210-E217}, pmid = {29279409}, issn = {1091-6490}, support = {P01 AI063302/AI/NIAID NIH HHS/United States ; R01 AI027655/AI/NIAID NIH HHS/United States ; R01 AI040646/AI/NIAID NIH HHS/United States ; R01 AI120694/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Autophagy ; Bacterial Proteins/genetics/metabolism ; Cells, Cultured ; Cytosol/metabolism/microbiology ; Host-Pathogen Interactions ; Listeria monocytogenes/genetics/*physiology ; Macrophages/metabolism/*microbiology ; Membrane Proteins/genetics/metabolism ; Mice, Knockout ; Mice, Transgenic ; Microscopy, Fluorescence ; Mutation ; *Phagocytosis ; Phagosomes/metabolism/microbiology ; Time-Lapse Imaging/methods ; Type C Phospholipases/genetics/metabolism ; }, abstract = {Xenophagy is a selective macroautophagic process that protects the host cytosol by entrapping and delivering microbes to a degradative compartment. Both noncanonical autophagic pathways and xenophagy are activated by microbes during infection, but the relative importance and function of these distinct processes are not clear. In this study, we used bacterial and host mutants to dissect the contribution of autophagic processes responsible for bacterial growth restriction of Listeria monocytogenesL. monocytogenes is a facultative intracellular pathogen that escapes from phagosomes, grows in the host cytosol, and avoids autophagy by expressing three determinants of pathogenesis: two secreted phospholipases C (PLCs; PlcA and PlcB) and a surface protein (ActA). We found that shortly after phagocytosis, wild-type (WT) L. monocytogenes escaped from a noncanonical autophagic process that targets damaged vacuoles. During this process, the autophagy marker LC3 localized to single-membrane phagosomes independently of the ULK complex, which is required for initiation of macroautophagy. However, growth restriction of bacteria lacking PlcA, PlcB, and ActA required FIP200 and TBK1, both involved in the engulfment of microbes by xenophagy. Time-lapse video microscopy revealed that deposition of LC3 on L. monocytogenes-containing vacuoles via noncanonical autophagy had no apparent role in restricting bacterial growth and that, upon access to the host cytosol, WT L. monocytogenes utilized PLCs and ActA to avoid subsequent xenophagy. In conclusion, although noncanonical autophagy targets phagosomes, xenophagy was required to restrict the growth of L. monocytogenes, an intracellular pathogen that damages the entry vacuole.}, } @article {pmid29279408, year = {2018}, author = {Beulig, F and Røy, H and Glombitza, C and Jørgensen, BB}, title = {Control on rate and pathway of anaerobic organic carbon degradation in the seabed.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {367-372}, pmid = {29279408}, issn = {1091-6490}, support = {294200//European Research Council/International ; }, mesh = {Acetates/metabolism ; Anaerobiosis ; Baltic States ; Carbon/*metabolism ; Carbon Dioxide/metabolism ; Geologic Sediments/chemistry/microbiology ; Hydrogen/metabolism ; Methane/metabolism ; Oceans and Seas ; Organic Chemicals/*metabolism ; Oxidation-Reduction ; Seawater/*microbiology ; Sulfates/metabolism ; *Water Microbiology ; }, abstract = {The degradation of organic matter in the anoxic seabed proceeds through a complex microbial network in which the terminal steps are dominated by oxidation with sulfate or conversion into methane and CO2 The controls on pathway and rate of the degradation process in different geochemical zones remain elusive. Radiotracer techniques were used to perform measurements of sulfate reduction, methanogenesis, and acetate oxidation with unprecedented sensitivity throughout Holocene sediment columns from the Baltic Sea. We found that degradation rates transition continuously from the sulfate to the methane zone, thereby demonstrating that terminal steps do not exert feedback control on upstream hydrolytic and fermentative processes, as previously suspected. Acetate was a key intermediate for carbon mineralization in both zones. However, acetate was not directly converted into methane. Instead, an additional subterminal step converted acetate to CO2 and reducing equivalents, such as H2, which then fed autotrophic reduction of CO2 to methane.}, } @article {pmid29279407, year = {2018}, author = {Łukasik, P and Nazario, K and Van Leuven, JT and Campbell, MA and Meyer, M and Michalik, A and Pessacq, P and Simon, C and Veloso, C and McCutcheon, JP}, title = {Multiple origins of interdependent endosymbiotic complexes in a genus of cicadas.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E226-E235}, pmid = {29279407}, issn = {1091-6490}, mesh = {Animals ; Bacteria/*classification/*genetics ; Bacterial Physiological Phenomena/*genetics ; Biological Evolution ; Chile ; Genetic Variation ; Genome, Bacterial ; Hemiptera/*microbiology ; Phylogeny ; Symbiosis/*physiology ; }, abstract = {Bacterial endosymbionts that provide nutrients to hosts often have genomes that are extremely stable in structure and gene content. In contrast, the genome of the endosymbiont Hodgkinia cicadicola has fractured into multiple distinct lineages in some species of the cicada genus Tettigades To better understand the frequency, timing, and outcomes of Hodgkinia lineage splitting throughout this cicada genus, we sampled cicadas over three field seasons in Chile and performed genomics and microscopy on representative samples. We found that a single ancestral Hodgkinia lineage has split at least six independent times in Tettigades over the last 4 million years, resulting in complexes of between two and six distinct Hodgkinia lineages per host. Individual genomes in these symbiotic complexes differ dramatically in relative abundance, genome size, organization, and gene content. Each Hodgkinia lineage retains a small set of core genes involved in genetic information processing, but the high level of gene loss experienced by all genomes suggests that extensive sharing of gene products among symbiont cells must occur. In total, Hodgkinia complexes that consist of multiple lineages encode nearly complete sets of genes present on the ancestral single lineage and presumably perform the same functions as symbionts that have not undergone splitting. However, differences in the timing of the splits, along with dissimilar gene loss patterns on the resulting genomes, have led to very different outcomes of lineage splitting in extant cicadas.}, } @article {pmid29279406, year = {2018}, author = {}, title = {Correction for Isik et al., Perceiving social interactions in the posterior superior temporal sulcus.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E113-E114}, doi = {10.1073/pnas.1721071115}, pmid = {29279406}, issn = {1091-6490}, } @article {pmid29279405, year = {2018}, author = {Sachan, AK and Zasadzinski, JA}, title = {Interfacial curvature effects on the monolayer morphology and dynamics of a clinical lung surfactant.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E134-E143}, pmid = {29279405}, issn = {1091-6490}, support = {R01 HL051177/HL/NHLBI NIH HHS/United States ; R01 HL135065/HL/NHLBI NIH HHS/United States ; }, mesh = {Adsorption ; Algorithms ; Animals ; Anisotropy ; Biological Products/chemistry ; Biophysical Phenomena ; Humans ; Lung/*chemistry ; *Membranes, Artificial ; Microscopy, Confocal ; Phospholipids/chemistry ; Pulmonary Surfactants/*chemistry ; Surface Properties ; Water/*chemistry ; }, abstract = {The morphology of surfactant monolayers is typically studied on the planar surface of a Langmuir trough, even though most physiological interfaces are curved at the micrometer scale. Here, we show that, as the radius of a clinical lung surfactant monolayer-covered bubble decreases to ∼100 µm, the monolayer morphology changes from dispersed circular liquid-condensed (LC) domains in a continuous liquid-expanded (LE) matrix to a continuous LC linear mesh separating discontinuous LE domains. The curvature-associated morphological transition cannot be readily explained by current liquid crystal theories based on isotropic domains. It is likely due to the anisotropic bending energy of the LC phase of the saturated phospholipids that are common to all natural and clinical lung surfactants. This continuous LC linear mesh morphology is also present on bilayer vesicles in solution. Surfactant adsorption and the dilatational modulus are also strongly influenced by the changes in morphology induced by interfacial curvature. The changes in morphology and dynamics may have physiological consequences for lung stability and function as the morphological transition occurs at alveolar dimensions.}, } @article {pmid29279404, year = {2018}, author = {Huang, C and Sun, H and Xu, D and Chen, Q and Liang, Y and Wang, X and Xu, G and Tian, J and Wang, C and Li, D and Wu, L and Yang, X and Jin, W and Doebley, JF and Tian, F}, title = {ZmCCT9 enhances maize adaptation to higher latitudes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E334-E341}, pmid = {29279404}, issn = {1091-6490}, mesh = {Adaptation, Physiological/*genetics ; Cloning, Molecular ; Flowers/genetics/physiology ; Gene Deletion ; Gene Expression Regulation, Plant/*physiology ; Genome, Plant ; Plant Proteins/genetics/*metabolism ; Transcription Factors/*metabolism ; Zea mays/*genetics/*physiology ; }, abstract = {From its tropical origin in southwestern Mexico, maize spread over a wide latitudinal cline in the Americas. This feat defies the rule that crops are inhibited from spreading easily across latitudes. How the widespread latitudinal adaptation of maize was accomplished is largely unknown. Through positional cloning and association mapping, we resolved a flowering-time quantitative trait locus to a Harbinger-like transposable element positioned 57 kb upstream of a CCT transcription factor (ZmCCT9). The Harbinger-like element acts in cis to repress ZmCCT9 expression to promote flowering under long days. Knockout of ZmCCT9 by CRISPR/Cas9 causes early flowering under long days. ZmCCT9 is diurnally regulated and negatively regulates the expression of the florigen ZCN8, thereby resulting in late flowering under long days. Population genetics analyses revealed that the Harbinger-like transposon insertion at ZmCCT9 and the CACTA-like transposon insertion at another CCT paralog, ZmCCT10, arose sequentially following domestication and were targeted by selection for maize adaptation to higher latitudes. Our findings help explain how the dynamic maize genome with abundant transposon activity enabled maize to adapt over 90° of latitude during the pre-Columbian era.}, } @article {pmid29279403, year = {2018}, author = {Pelt, DM and Sethian, JA}, title = {A mixed-scale dense convolutional neural network for image analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {254-259}, pmid = {29279403}, issn = {1091-6490}, support = {P41 GM103445/GM/NIGMS NIH HHS/United States ; U01 DA040582/DA/NIDA NIH HHS/United States ; }, mesh = {Algorithms ; Computer Simulation ; Diagnostic Imaging/*methods ; *Machine Learning ; *Models, Theoretical ; *Neural Networks (Computer) ; }, abstract = {Deep convolutional neural networks have been successfully applied to many image-processing problems in recent works. Popular network architectures often add additional operations and connections to the standard architecture to enable training deeper networks. To achieve accurate results in practice, a large number of trainable parameters are often required. Here, we introduce a network architecture based on using dilated convolutions to capture features at different image scales and densely connecting all feature maps with each other. The resulting architecture is able to achieve accurate results with relatively few parameters and consists of a single set of operations, making it easier to implement, train, and apply in practice, and automatically adapts to different problems. We compare results of the proposed network architecture with popular existing architectures for several segmentation problems, showing that the proposed architecture is able to achieve accurate results with fewer parameters, with a reduced risk of overfitting the training data.}, } @article {pmid29279402, year = {2018}, author = {Aymeric, L and Donnadieu, F and Mulet, C and du Merle, L and Nigro, G and Saffarian, A and Bérard, M and Poyart, C and Robine, S and Regnault, B and Trieu-Cuot, P and Sansonetti, PJ and Dramsi, S}, title = {Colorectal cancer specific conditions promote Streptococcus gallolyticus gut colonization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E283-E291}, pmid = {29279402}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Adenoma ; Animals ; Bacteriocins/genetics/metabolism ; Bile Acids and Salts/metabolism ; Colorectal Neoplasms/*metabolism ; Gastrointestinal Tract/*microbiology ; Gene Expression Regulation ; Humans ; Mice ; Organic Anion Transporters, Sodium-Dependent/genetics/metabolism ; Receptors, Notch/genetics/metabolism ; Streptococcus gallolyticus/*physiology ; Symporters/genetics/metabolism ; }, abstract = {Colonization by Streptococcus gallolyticus subsp. gallolyticus (SGG) is strongly associated with the occurrence of colorectal cancer (CRC). However, the factors leading to its successful colonization are unknown, and whether SGG influences the oncogenic process or benefits from the tumor-prone environment to prevail remains an open question. Here, we elucidate crucial steps that explain how CRC favors SGG colonization. By using mice genetically prone to CRC, we show that SGG colonization is 1,000-fold higher in tumor-bearing mice than in normal mice. This selective advantage occurs at the expense of resident intestinal enterococci. An SGG-specific locus encoding a bacteriocin ("gallocin") is shown to kill enterococci in vitro. Importantly, bile acids strongly enhance this bacteriocin activity in vivo, leading to greater SGG colonization. Constitutive activation of the Wnt pathway, one of the earliest signaling alterations in CRC, and the decreased expression of the bile acid apical transporter gene Slc10A2, as an effect of the Apc founding mutation, may thereby sustain intestinal colonization by SGG. We conclude that CRC-specific conditions promote SGG colonization of the gut by replacing commensal enterococci in their niche.}, } @article {pmid29279401, year = {2018}, author = {Lu, WJ and Mann, RK and Nguyen, A and Bi, T and Silverstein, M and Tang, JY and Chen, X and Beachy, PA}, title = {Neuronal delivery of Hedgehog directs spatial patterning of taste organ regeneration.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E200-E209}, pmid = {29279401}, issn = {1091-6490}, support = {R21 NS093556/NS/NINDS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Epithelium/growth & development/*metabolism/physiology ; Gene Expression Regulation, Developmental ; Hedgehog Proteins/genetics/*metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Organogenesis/genetics ; Regeneration/genetics ; Signal Transduction/genetics ; Taste/genetics ; Taste Buds/cytology/growth & development/*metabolism ; Time Factors ; Tongue/cytology/growth & development/*metabolism ; }, abstract = {How organs maintain and restore functional integrity during ordinary tissue turnover or following injury represents a central biological problem. The maintenance of taste sensory organs in the tongue was shown 140 years ago to depend on innervation from distant ganglion neurons, but the underlying mechanism has remained unknown. Here, we show that Sonic hedgehog (Shh), which encodes a secreted protein signal, is expressed in these sensory neurons, and that experimental ablation of neuronal Shh expression causes loss of taste receptor cells (TRCs). TRCs are also lost upon pharmacologic blockade of Hedgehog pathway response, accounting for the loss of taste sensation experienced by cancer patients undergoing Hedgehog inhibitor treatment. We find that TRC regeneration following such pharmacologic ablation requires neuronal expression of Shh and can be substantially enhanced by pharmacologic activation of Hedgehog response. Such pharmacologic enhancement of Hedgehog response, however, results in additional TRC formation at many ectopic sites, unlike the site-restricted regeneration specified by the projection pattern of Shh-expressing neurons. Stable regeneration of TRCs thus requires neuronal Shh, illustrating the principle that neuronal delivery of cues such as the Shh signal can pattern distant cellular responses to assure functional integrity during tissue maintenance and regeneration.}, } @article {pmid29279400, year = {2018}, author = {Ma, T and Wang, K and Hu, Q and Xi, Z and Wan, D and Wang, Q and Feng, J and Jiang, D and Ahani, H and Abbott, RJ and Lascoux, M and Nevo, E and Liu, J}, title = {Ancient polymorphisms and divergence hitchhiking contribute to genomic islands of divergence within a poplar species complex.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E236-E243}, pmid = {29279400}, issn = {1091-6490}, mesh = {*Biological Evolution ; Chromosome Mapping ; Chromosomes, Plant/genetics ; *Genetic Speciation ; Genome, Plant ; *Genomic Islands ; *Polymorphism, Genetic ; Populus/*genetics ; }, abstract = {How genome divergence eventually leads to speciation is a topic of prime evolutionary interest. Genomic islands of elevated divergence are frequently reported between diverging lineages, and their size is expected to increase with time and gene flow under the speciation-with-gene-flow model. However, such islands can also result from divergent sorting of ancient polymorphisms, recent ecological selection regardless of gene flow, and/or recurrent background selection and selective sweeps in low-recombination regions. It is challenging to disentangle these nonexclusive alternatives, but here we attempt to do this in an analysis of what drove genomic divergence between four lineages comprising a species complex of desert poplar trees. Within this complex we found that two morphologically delimited species, Populus euphratica and Populus pruinosa, were paraphyletic while the four lineages exhibited contrasting levels of gene flow and divergence times, providing a good system for testing hypotheses on the origin of divergence islands. We show that the size and number of genomic islands that distinguish lineages are not associated with either rate of recent gene flow or time of divergence. Instead, they are most likely derived from divergent sorting of ancient polymorphisms and divergence hitchhiking. We found that highly diverged genes under lineage-specific selection and putatively involved in ecological and morphological divergence occur both within and outside these islands. Our results highlight the need to incorporate demography, absolute divergence measurement, and gene flow rate to explain the formation of genomic islands and to identify potential genomic regions involved in speciation.}, } @article {pmid29279399, year = {2018}, author = {Felice, RN and Goswami, A}, title = {Developmental origins of mosaic evolution in the avian cranium.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {555-560}, pmid = {29279399}, issn = {1091-6490}, mesh = {Animals ; *Biological Evolution ; Birds/anatomy & histology/classification/*genetics/growth & development ; *Mosaicism ; Phenotype ; Phylogeny ; Skull/anatomy & histology/*growth & development ; }, abstract = {Mosaic evolution, which results from multiple influences shaping morphological traits and can lead to the presence of a mixture of ancestral and derived characteristics, has been frequently invoked in describing evolutionary patterns in birds. Mosaicism implies the hierarchical organization of organismal traits into semiautonomous subsets, or modules, which reflect differential genetic and developmental origins. Here, we analyze mosaic evolution in the avian skull using high-dimensional 3D surface morphometric data across a broad phylogenetic sample encompassing nearly all extant families. We find that the avian cranium is highly modular, consisting of seven independently evolving anatomical regions. The face and cranial vault evolve faster than other regions, showing several bursts of rapid evolution. Other modules evolve more slowly following an early burst. Both the evolutionary rate and disparity of skull modules are associated with their developmental origin, with regions derived from the anterior mandibular-stream cranial neural crest or from multiple embryonic cell populations evolving most quickly and into a greater variety of forms. Strong integration of traits is also associated with low evolutionary rate and low disparity. Individual clades are characterized by disparate evolutionary rates among cranial regions. For example, Psittaciformes (parrots) exhibit high evolutionary rates throughout the skull, but their close relatives, Falconiformes, exhibit rapid evolution in only the rostrum. Our dense sampling of cranial shape variation demonstrates that the bird skull has evolved in a mosaic fashion reflecting the developmental origins of cranial regions, with a semi-independent tempo and mode of evolution across phenotypic modules facilitating this hyperdiverse evolutionary radiation.}, } @article {pmid29279398, year = {2018}, author = {Barrera-Guzmán, AO and Aleixo, A and Shawkey, MD and Weir, JT}, title = {Hybrid speciation leads to novel male secondary sexual ornamentation of an Amazonian bird.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E218-E225}, pmid = {29279398}, issn = {1091-6490}, mesh = {Animal Distribution ; Animals ; Carotenoids/metabolism ; Feathers/physiology ; Female ; *Genetic Speciation ; Genome-Wide Association Study ; *Hybridization, Genetic ; Keratins/physiology ; Male ; Passeriformes/*genetics/physiology ; Polymorphism, Single Nucleotide ; Sex Characteristics ; South Africa ; South America ; }, abstract = {Hybrid speciation is rare in vertebrates, and reproductive isolation arising from hybridization is infrequently demonstrated. Here, we present evidence supporting a hybrid-speciation event involving the genetic admixture of the snow-capped (Lepidothrix nattereri) and opal-crowned (Lepidothrix iris) manakins of the Amazon basin, leading to the formation of the hybrid species, the golden-crowned manakin (Lepidothrix vilasboasi). We used a genome-wide SNP dataset together with analysis of admixture, population structure, and coalescent modeling to demonstrate that the golden-crowned manakin is genetically an admixture of these species and does not represent a hybrid zone but instead formed through ancient genetic admixture. We used spectrophotometry to quantify the coloration of the species-specific male crown patches. Crown patches are highly reflective white (snow-capped manakin) or iridescent whitish-blue to pink (opal-crowned manakin) in parental species but are a much less reflective yellow in the hybrid species. The brilliant coloration of the parental species results from nanostructural organization of the keratin matrix feather barbs of the crown. However, using electron microscopy, we demonstrate that the structural organization of this matrix is different in the two parental species and that the hybrid species is intermediate. The intermediate nature of the crown barbs, resulting from past admixture appears to have rendered a duller structural coloration. To compensate for reduced brightness, selection apparently resulted in extensive thickening of the carotenoid-laden barb cortex, producing the yellow crown coloration. The evolution of this unique crown-color signal likely culminated in premating isolation of the hybrid species from both parental species.}, } @article {pmid29279397, year = {2018}, author = {Viegas, J}, title = {Profile of David M. Sabatini.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {438-440}, pmid = {29279397}, issn = {1091-6490}, mesh = {Cell Biology/*history ; History, 20th Century ; History, 21st Century ; Humans ; Signal Transduction ; Sirolimus/pharmacology ; Streptomyces/drug effects/genetics/metabolism ; TOR Serine-Threonine Kinases/genetics/*metabolism ; United States ; }, } @article {pmid29279396, year = {2018}, author = {Bergdoll, LA and Lerch, MT and Patrick, JW and Belardo, K and Altenbach, C and Bisignano, P and Laganowsky, A and Grabe, M and Hubbell, WL and Abramson, J}, title = {Protonation state of glutamate 73 regulates the formation of a specific dimeric association of mVDAC1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E172-E179}, pmid = {29279396}, issn = {1091-6490}, support = {P30 EY000331/EY/NEI NIH HHS/United States ; R25 GM055052/GM/NIGMS NIH HHS/United States ; R01 GM089740/GM/NIGMS NIH HHS/United States ; R01 EY005216/EY/NEI NIH HHS/United States ; DP2 GM123486/GM/NIGMS NIH HHS/United States ; R01 GM078844/GM/NIGMS NIH HHS/United States ; }, mesh = {Algorithms ; Animals ; Glutamates/*chemistry/genetics/metabolism ; Hydrogen-Ion Concentration ; Kinetics ; Mice ; Models, Molecular ; Mutation ; Protein Conformation ; *Protein Multimerization ; *Protons ; Voltage-Dependent Anion Channel 1/*chemistry/genetics/metabolism ; }, abstract = {The voltage-dependent anion channel (VDAC) is the most abundant protein in the outer mitochondrial membrane and constitutes the primary pathway for the exchange of ions and metabolites between the cytosol and the mitochondria. There is accumulating evidence supporting VDAC's role in mitochondrial metabolic regulation and apoptosis, where VDAC oligomerization has been implicated with these processes. Herein, we report a specific pH-dependent dimerization of murine VDAC1 (mVDAC1) identified by double electron-electron resonance and native mass spectrometry. Intermolecular distances on four singly spin-labeled mVDAC1 mutants were used to generate a model of the low-pH dimer, establishing the presence of residue E73 at the interface. This dimer arrangement is different from any oligomeric state previously described, and it forms as a steep function of pH with an apparent pKa of 7.4. Moreover, the monomer-dimer equilibrium affinity constant was determined using native MS, revealing a nearly eightfold enhancement in dimerization affinity at low pH. Mutation of E73 to either alanine or glutamine severely reduces oligomerization, demonstrating the role of protonated E73 in enhancing dimer formation. Based on these results, and the known importance of E73 in VDAC physiology, VDAC dimerization likely plays a significant role in mitochondrial metabolic regulation and apoptosis in response to cytosolic acidification during cellular stress.}, } @article {pmid29279395, year = {2018}, author = {Ferron, F and Subissi, L and Silveira De Morais, AT and Le, NTT and Sevajol, M and Gluais, L and Decroly, E and Vonrhein, C and Bricogne, G and Canard, B and Imbert, I}, title = {Structural and molecular basis of mismatch correction and ribavirin excision from coronavirus RNA.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E162-E171}, pmid = {29279395}, issn = {1091-6490}, mesh = {Antiviral Agents/metabolism/pharmacology ; Coronavirus/drug effects/genetics/*metabolism ; Crystallography, X-Ray ; Exoribonucleases/chemistry/genetics/metabolism ; Humans ; Methyltransferases/chemistry/genetics/metabolism ; Models, Molecular ; Protein Binding ; Protein Domains ; RNA, Viral/genetics/*metabolism ; Ribavirin/*metabolism/pharmacology ; Severe Acute Respiratory Syndrome/virology ; Viral Nonstructural Proteins/chemistry/genetics/metabolism ; *Virus Replication ; }, abstract = {Coronaviruses (CoVs) stand out among RNA viruses because of their unusually large genomes (∼30 kb) associated with low mutation rates. CoVs code for nsp14, a bifunctional enzyme carrying RNA cap guanine N7-methyltransferase (MTase) and 3'-5' exoribonuclease (ExoN) activities. ExoN excises nucleotide mismatches at the RNA 3'-end in vitro, and its inactivation in vivo jeopardizes viral genetic stability. Here, we demonstrate for severe acute respiratory syndrome (SARS)-CoV an RNA synthesis and proofreading pathway through association of nsp14 with the low-fidelity nsp12 viral RNA polymerase. Through this pathway, the antiviral compound ribavirin 5'-monophosphate is significantly incorporated but also readily excised from RNA, which may explain its limited efficacy in vivo. The crystal structure at 3.38 Å resolution of SARS-CoV nsp14 in complex with its cofactor nsp10 adds to the uniqueness of CoVs among RNA viruses: The MTase domain presents a new fold that differs sharply from the canonical Rossmann fold.}, } @article {pmid29279394, year = {2018}, author = {Woerman, AL and Kazmi, SA and Patel, S and Aoyagi, A and Oehler, A and Widjaja, K and Mordes, DA and Olson, SH and Prusiner, SB}, title = {Familial Parkinson's point mutation abolishes multiple system atrophy prion replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {409-414}, pmid = {29279394}, issn = {1091-6490}, support = {P01 AG002132/AG/NIA NIH HHS/United States ; P50 AG005134/AG/NIA NIH HHS/United States ; R37 AG031220/AG/NIA NIH HHS/United States ; }, mesh = {Animals ; Cell Line ; HEK293 Cells ; Humans ; Mice, Transgenic ; Multiple System Atrophy/*genetics ; Parkinson Disease/*genetics ; *Point Mutation ; Prions/*genetics/metabolism/pathogenicity ; Protein Folding ; alpha-Synuclein/chemistry/genetics/metabolism ; }, abstract = {In the neurodegenerative disease multiple system atrophy (MSA), α-synuclein misfolds into a self-templating conformation to become a prion. To compare the biological activity of α-synuclein prions in MSA and Parkinson's disease (PD), we developed nine α-synuclein-YFP cell lines expressing point mutations responsible for inherited PD. MSA prions robustly infected wild-type, A30P, and A53T α-synuclein-YFP cells, but they were unable to replicate in cells expressing the E46K mutation. Coexpression of the A53T and E46K mutations was unable to rescue MSA prion infection in vitro, establishing that MSA α-synuclein prions are conformationally distinct from the misfolded α-synuclein in PD patients. This observation may have profound implications for developing treatments for neurodegenerative diseases.}, } @article {pmid29279393, year = {2018}, author = {An, D and Chiu, A and Flanders, JA and Song, W and Shou, D and Lu, YC and Grunnet, LG and Winkel, L and Ingvorsen, C and Christophersen, NS and Fels, JJ and Sand, FW and Ji, Y and Qi, L and Pardo, Y and Luo, D and Silberstein, M and Fan, J and Ma, M}, title = {Designing a retrievable and scalable cell encapsulation device for potential treatment of type 1 diabetes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E263-E272}, pmid = {29279393}, issn = {1091-6490}, support = {P30 DK020572/DK/NIDDK NIH HHS/United States ; }, mesh = {Alginates ; Animals ; *Cell- and Tissue-Based Therapy ; Diabetes Mellitus, Experimental/therapy ; Dimethylformamide ; Dogs ; Glucuronic Acid ; Hexuronic Acids ; Humans ; Hydrogels ; Islets of Langerhans/*physiology ; Islets of Langerhans Transplantation/*methods ; Mice ; Mice, SCID ; Polymethyl Methacrylate ; Rats ; }, abstract = {Cell encapsulation has been shown to hold promise for effective, long-term treatment of type 1 diabetes (T1D). However, challenges remain for its clinical applications. For example, there is an unmet need for an encapsulation system that is capable of delivering sufficient cell mass while still allowing convenient retrieval or replacement. Here, we report a simple cell encapsulation design that is readily scalable and conveniently retrievable. The key to this design was to engineer a highly wettable, Ca2+-releasing nanoporous polymer thread that promoted uniform in situ cross-linking and strong adhesion of a thin layer of alginate hydrogel around the thread. The device provided immunoprotection of rat islets in immunocompetent C57BL/6 mice in a short-term (1-mo) study, similar to neat alginate fibers. However, the mechanical property of the device, critical for handling and retrieval, was much more robust than the neat alginate fibers due to the reinforcement of the central thread. It also had facile mass transfer due to the short diffusion distance. We demonstrated the therapeutic potential of the device through the correction of chemically induced diabetes in C57BL/6 mice using rat islets for 3 mo as well as in immunodeficient SCID-Beige mice using human islets for 4 mo. We further showed, as a proof of concept, the scalability and retrievability in dogs. After 1 mo of implantation in dogs, the device could be rapidly retrieved through a minimally invasive laparoscopic procedure. This encapsulation device may contribute to a cellular therapy for T1D because of its retrievability and scale-up potential.}, } @article {pmid29279392, year = {2018}, author = {Jiang, YL and Wang, XP and Sun, H and Han, SJ and Li, WF and Cui, N and Lin, GM and Zhang, JY and Cheng, W and Cao, DD and Zhang, ZY and Zhang, CC and Chen, Y and Zhou, CZ}, title = {Coordinating carbon and nitrogen metabolic signaling through the cyanobacterial global repressor NdhR.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {403-408}, pmid = {29279392}, issn = {1091-6490}, mesh = {Bacterial Proteins/genetics/metabolism ; Carbon/*metabolism ; Carbon Dioxide/metabolism ; Cyanobacteria/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; *Genes, Regulator ; Glycolates/metabolism ; Ketoglutaric Acids/metabolism ; NAD(P)H Dehydrogenase (Quinone)/genetics/*metabolism ; Nitrogen/*metabolism ; Ribulose-Bisphosphate Carboxylase/genetics/metabolism ; Signal Transduction ; }, abstract = {The coordination of carbon and nitrogen metabolism is essential for bacteria to adapt to nutritional variations in the environment, but the underlying mechanism remains poorly understood. In autotrophic cyanobacteria, high CO2 levels favor the carboxylase activity of ribulose 1,5 bisphosphate carboxylase/oxygenase (RuBisCO) to produce 3-phosphoglycerate, whereas low CO2 levels promote the oxygenase activity of RuBisCO, leading to 2-phosphoglycolate (2-PG) production. Thus, the 2-PG level is reversely correlated with that of 2-oxoglutarate (2-OG), which accumulates under a high carbon/nitrogen ratio and acts as a nitrogen-starvation signal. The LysR-type transcriptional repressor NAD(P)H dehydrogenase regulator (NdhR) controls the expression of genes related to carbon metabolism. Based on genetic and biochemical studies, we report here that 2-PG is an inducer of NdhR, while 2-OG is a corepressor, as found previously. Furthermore, structural analyses indicate that binding of 2-OG at the interface between the two regulatory domains (RD) allows the NdhR tetramer to adopt a repressor conformation, whereas 2-PG binding to an intradomain cleft of each RD triggers drastic conformational changes leading to the dissociation of NdhR from its target DNA. We further confirmed the effect of 2-PG or 2-OG levels on the transcription of the NdhR regulon. Together with previous findings, we propose that NdhR can sense 2-OG from the Krebs cycle and 2-PG from photorespiration, two key metabolites that function together as indicators of intracellular carbon/nitrogen status, thus representing a fine sensor for the coordination of carbon and nitrogen metabolism in cyanobacteria.}, } @article {pmid29279391, year = {2018}, author = {Whyte, JJ and Meyer, AE and Spate, LD and Benne, JA and Cecil, R and Samuel, MS and Murphy, CN and Prather, RS and Geisert, RD}, title = {Inactivation of porcine interleukin-1β results in failure of rapid conceptus elongation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {307-312}, pmid = {29279391}, issn = {1091-6490}, support = {U42 OD011140/OD/NIH HHS/United States ; }, mesh = {Animals ; CRISPR-Cas Systems ; Cell Proliferation/*genetics ; Cyclooxygenase 2/genetics/metabolism ; Endometrium/metabolism ; Estrogens/metabolism ; Female ; Gene Expression Regulation, Developmental ; Interleukin-1beta/*genetics/metabolism ; Pregnancy ; Swine ; Time Factors ; Trophoblasts/cytology/*metabolism ; Uterus/*metabolism ; }, abstract = {Conceptus expansion throughout the uterus of mammalian species with a noninvasive epitheliochorial type of placentation is critical establishing an adequate uterine surface area for nutrient support during gestation. Pig conceptuses undergo a unique rapid morphological transformation to elongate into filamentous threads within 1 h, which provides the uterine surface to support development and maintain functional corpora lutea through the production of estrogen. Conceptus production of a unique interleukin 1β, IL1B2, temporally increases during the period of trophoblast remodeling during elongation. CRISPR/Cas9 gene editing was used to knock out pig conceptus IL1B2 expression and the secretion of IL1B2 during the time of conceptus elongation. Trophoblast elongation occurred on day 14 in wild-type (IL1B2+/+) conceptuses but did not occur in ILB2-null (IL1B2-/-) conceptuses. Although the morphological transition of IL1B2-/- conceptuses was inhibited, expression of a number of conceptus developmental genes was not altered. However, conceptus aromatase expression and estrogen secretion were decreased, indicating that IL1B2 may be involved in the spatiotemporal increase in conceptus estrogen synthesis needed for the establishment of pregnancy in the pig and may serve to regulate the proinflammatory response of endometrium to IL1B2 during conceptus elongation and attachment to the uterine surface.}, } @article {pmid29279390, year = {2018}, author = {Wagatsuma, A and Okuyama, T and Sun, C and Smith, LM and Abe, K and Tonegawa, S}, title = {Locus coeruleus input to hippocampal CA3 drives single-trial learning of a novel context.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E310-E316}, pmid = {29279390}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Behavior, Animal ; Calcium/metabolism ; Dentate Gyrus ; Hippocampus/*physiology ; Locus Coeruleus/*physiology ; Male ; Memory/*physiology ; Mice ; Neural Pathways/physiology ; Neurons/physiology ; Temporal Lobe ; }, abstract = {The memory for a new episode is formed immediately upon experience and can last up to a lifetime. It has been shown that the hippocampal network plays a fundamental role in the rapid acquisition of a memory of a one-time experience, in which the novelty component of the experience promotes the prompt formation of the memory. However, it remains unclear which neural circuits convey the novelty signal to the hippocampus for the single-trial learning. Here, we show that during encoding neuromodulatory input from locus coeruleus (LC) to CA3, but not CA1 or to the dentate gyrus, is necessary to facilitate novel contextual learning. Silencing LC activity during exposure to a novel context reduced subsequent reactivation of the engram cell ensembles in CA3 neurons and in downstream CA1 upon reexposure to the same context. Calcium imaging of the cells reactivated in both novel and familiar contexts revealed that suppression of LC inputs at the time of encoding resulted in more variable place fields in CA3 neurons. These results suggest that neuromodulatory input from LC to CA3 is crucial for the formation of a persistent memory in the hippocampus.}, } @article {pmid29279389, year = {2018}, author = {Shi, GX and Yang, WS and Jin, L and Matter, ML and Ramos, JW}, title = {RSK2 drives cell motility by serine phosphorylation of LARG and activation of Rho GTPases.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E190-E199}, pmid = {29279389}, issn = {1091-6490}, support = {P30 CA071789/CA/NCI NIH HHS/United States ; R01 GM088266/GM/NIGMS NIH HHS/United States ; R01 GM104984/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; *Cell Movement ; Enzyme Activation ; HEK293 Cells ; Humans ; Mutation ; Phosphorylation ; RNA Interference ; Rho Guanine Nucleotide Exchange Factors/genetics/*metabolism ; Ribosomal Protein S6 Kinases, 90-kDa/genetics/*metabolism ; Serine/genetics/*metabolism ; Signal Transduction/genetics ; Threonine/metabolism ; rho GTP-Binding Proteins/genetics/*metabolism ; }, abstract = {Directed migration is essential for cell motility in many processes, including development and cancer cell invasion. RSKs (p90 ribosomal S6 kinases) have emerged as central regulators of cell migration; however, the mechanisms mediating RSK-dependent motility remain incompletely understood. We have identified a unique signaling mechanism by which RSK2 promotes cell motility through leukemia-associated RhoGEF (LARG)-dependent Rho GTPase activation. RSK2 directly interacts with LARG and nucleotide-bound Rho isoforms, but not Rac1 or Cdc42. We further show that epidermal growth factor or FBS stimulation induces association of endogenous RSK2 with LARG and LARG with RhoA. In response to these stimuli, RSK2 phosphorylates LARG at Ser1288 and thereby activates RhoA. Phosphorylation of RSK2 at threonine 577 is essential for activation of LARG-RhoA. Moreover, RSK2-mediated motility signaling depends on RhoA and -B, but not RhoC. These results establish a unique RSK2-dependent LARG-RhoA signaling module as a central organizer of directed cell migration and invasion.}, } @article {pmid29279388, year = {2018}, author = {Zhang, F and Jara-Oseguera, A and Chang, TH and Bae, C and Hanson, SM and Swartz, KJ}, title = {Heat activation is intrinsic to the pore domain of TRPV1.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E317-E324}, pmid = {29279388}, issn = {1091-6490}, mesh = {Amino Acid Sequence ; Animals ; Binding Sites ; Gene Expression Regulation ; HEK293 Cells ; Humans ; Mice ; Models, Molecular ; Protein Conformation ; Protein Domains ; Rats ; Recombinant Fusion Proteins ; Shaker Superfamily of Potassium Channels/*metabolism ; TRPV Cation Channels/*metabolism ; }, abstract = {The TRPV1 channel is a sensitive detector of pain-producing stimuli, including noxious heat, acid, inflammatory mediators, and vanilloid compounds. Although binding sites for some activators have been identified, the location of the temperature sensor remains elusive. Using available structures of TRPV1 and voltage-activated potassium channels, we engineered chimeras wherein transmembrane regions of TRPV1 were transplanted into the Shaker Kv channel. Here we show that transplanting the pore domain of TRPV1 into Shaker gives rise to functional channels that can be activated by a TRPV1-selective tarantula toxin that binds to the outer pore of the channel. This pore-domain chimera is permeable to Na+, K+, and Ca2+ ions, and remarkably, is also robustly activated by noxious heat. Our results demonstrate that the pore of TRPV1 is a transportable domain that contains the structural elements sufficient for activation by noxious heat.}, } @article {pmid29279387, year = {2018}, author = {}, title = {Retraction for Jayandharan et al., Activation of the NF-κB pathway by adeno-associated virus (AAV) vectors and its implications in immune response and gene therapy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E343}, doi = {10.1073/pnas.1720655115}, pmid = {29279387}, issn = {1091-6490}, } @article {pmid29279386, year = {2018}, author = {Wang, Y and Wang, D and Dares, CJ and Marquard, SL and Sheridan, MV and Meyer, TJ}, title = {CO2 reduction to acetate in mixtures of ultrasmall (Cu) n ,(Ag) m bimetallic nanoparticles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {278-283}, pmid = {29279386}, issn = {1091-6490}, abstract = {Monodispersed mixtures of 6-nm Cu and Ag nanoparticles were prepared by electrochemical reduction on electrochemically polymerized poly-Fe(vbpy)3(PF6)2 film electrodes on glassy carbon. Conversion of the complex to poly-Fe(vbpy)2(CN)2 followed by surface binding of salts of the cations and electrochemical reduction gave a mixture of chemically distinct clusters on the surface, (Cu) m ,(Ag) n |polymer|glassy carbon electrode (GCE), as shown by X-ray photoelectron spectroscopy (XPS) measurements. A (Cu)2,(Ag)3|(80-monolayer-poly-Fe(vbpy)32+|GCE electrode at -1.33 V vs. reversible hydrogen electrode (RHE) in 0.5 M KHCO3, with 8 ppm added benzotriazole (BTA) at 0 °C, gave acetate with a faradaic efficiency of 21.2%.}, } @article {pmid29279385, year = {2018}, author = {Liang, L and Zhao, H and An, B and Tang, L}, title = {High-resolution structure of podovirus tail adaptor suggests repositioning of an octad motif that mediates the sequential tail assembly.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {313-318}, pmid = {29279385}, issn = {1091-6490}, support = {P30 GM103326/GM/NIGMS NIH HHS/United States ; R01 GM090010/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Motifs/genetics ; Amino Acid Sequence ; Bacteriophage P22/genetics/metabolism ; Crystallography, X-Ray ; Models, Molecular ; Podoviridae/genetics/*metabolism ; Protein Conformation ; Sequence Homology, Amino Acid ; Viral Tail Proteins/*chemistry/genetics/*metabolism ; *Virus Assembly ; }, abstract = {The sophisticated tail structures of DNA bacteriophages play essential roles in life cycles. Podoviruses P22 and Sf6 have short tails consisting of multiple proteins, among which is a tail adaptor protein that connects the portal protein to the other tail proteins. Assembly of the tail has been shown to occur in a sequential manner to ensure proper molecular interactions, but the underlying mechanism remains to be understood. Here, we report the high-resolution structure of the tail adaptor protein gp7 from phage Sf6. The structure exhibits distinct distribution of opposite charges on two sides of the molecule. A gp7 dodecameric ring model shows an entirely negatively charged surface, suggesting that the assembly of the dodecamer occurs through head-to-tail interactions of the bipolar monomers. The N-terminal helix-loop structure undergoes rearrangement compared with that of the P22 homolog complexed with the portal, which is achieved by repositioning of two consecutive repeats of a conserved octad sequence motif. We propose that the conformation of the N-terminal helix-loop observed in the Sf6-gp7 and P22 portal:gp4 complex represents the pre- and postassembly state, respectively. Such motif repositioning may serve as a conformational switch that creates the docking site for the tail nozzle only after the assembly of adaptor protein to the portal. In addition, the C-terminal portion of gp7 shows conformational flexibility, indicating an induced fit on binding to the portal. These results provide insight into the mechanistic role of the adaptor protein in mediating the sequential assembly of the phage tail.}, } @article {pmid29279384, year = {2018}, author = {Sluysmans, D and Devaux, F and Bruns, CJ and Stoddart, JF and Duwez, AS}, title = {Dynamic force spectroscopy of synthetic oligorotaxane foldamers.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9362-9366}, pmid = {29279384}, issn = {1091-6490}, abstract = {Wholly synthetic molecules involving both mechanical bonds and a folded secondary structure are one of the most promising architectures for the design of functional molecular machines with unprecedented properties. Here, we report dynamic single-molecule force spectroscopy experiments that explore the energetic details of donor-acceptor oligorotaxane foldamers, a class of molecular switches. The mechanical breaking of the donor-acceptor interactions responsible for the folded structure shows a high constant rupture force over a broad range of loading rates, covering three orders of magnitude. In comparison with dynamic force spectroscopy performed during the past 20 y on various (bio)molecules, the near-equilibrium regime of oligorotaxanes persists at much higher loading rates, at which biomolecules have reached their kinetic regime, illustrating the very fast dynamics and remarkable rebinding capabilities of the intramolecular donor-acceptor interactions. We focused on one single interaction at a time and probed the stochastic rupture and rebinding paths. Using the Crooks fluctuation theorem, we measured the mechanical work produced during the breaking and rebinding to determine a free-energy difference, ΔG, of 6 kcal·mol-1 between the two local conformations around a single bond.}, } @article {pmid29279383, year = {2018}, author = {Schout, G and Hartog, N and Hassanizadeh, SM and Griffioen, J}, title = {Impact of an historic underground gas well blowout on the current methane chemistry in a shallow groundwater system.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {296-301}, pmid = {29279383}, issn = {1091-6490}, abstract = {Blowouts present a small but genuine risk when drilling into the deep subsurface and can have an immediate and significant impact on the surrounding environment. Nevertheless, studies that document their long-term impact are scarce. In 1965, a catastrophic underground blowout occurred during the drilling of a gas well in The Netherlands, which led to the uncontrolled release of large amounts of natural gas from the reservoir to the surface. In this study, the remaining impact on methane chemistry in the overlying aquifers was investigated. Methane concentrations higher than 10 mg/L (n = 12) were all found to have δ13C-CH4 values larger than -30‰, typical of a thermogenic origin. Both δ13C-CH4 and δD-CH4 correspond to the isotopic composition of the gas reservoir. Based on analysis of local groundwater flow conditions, this methane is not a remnant but most likely the result of ongoing leakage from the reservoir as a result of the blowout. Progressive enrichment of both δ13C-CH4 and δD-CH4 is observed with increasing distance and decreasing methane concentrations. The calculated isotopic fractionation factors of εC = 3 and εD = 54 suggest anaerobic methane oxidation is partly responsible for the observed decrease in concentrations. Elevated dissolved iron and manganese concentrations at the fringe of the methane plume show that oxidation is primarily mediated by the reduction of iron and manganese oxides. Combined, the data reveal the long-term impact that underground gas well blowouts may have on groundwater chemistry, as well as the important role of anaerobic oxidation in controlling the fate of dissolved methane.}, } @article {pmid29279382, year = {2018}, author = {Li, Y and Jin, K and Bunker, E and Zhang, X and Luo, X and Liu, X and Hao, B}, title = {Structural basis of the phosphorylation-independent recognition of cyclin D1 by the SCFFBXO31 ubiquitin ligase.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {319-324}, pmid = {29279382}, issn = {1091-6490}, support = {S10 RR026680/RR/NCRR NIH HHS/United States ; S10 OD021601/OD/NIH HHS/United States ; T32 GM008759/GM/NIGMS NIH HHS/United States ; R01 GM099948/GM/NIGMS NIH HHS/United States ; R01 GM113141/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Crystallography, X-Ray ; Cyclin D1/*chemistry/genetics/metabolism ; F-Box Proteins/*chemistry/genetics/metabolism ; HeLa Cells ; Humans ; Models, Molecular ; Multiprotein Complexes/*chemistry/metabolism ; Phosphorylation ; Protein Binding ; *Protein Domains ; Proteolysis ; Sequence Homology, Amino Acid ; Substrate Specificity ; Tumor Suppressor Proteins/*chemistry/genetics/metabolism ; Ubiquitination ; }, abstract = {Ubiquitin-dependent proteolysis of cyclin D1 is associated with normal and tumor cell proliferation and survival. The SCFFBXO31 (Skp1-Cul1-Rbx1-FBXO31) ubiquitin ligase complex mediates genotoxic stress-induced cyclin D1 degradation. Previous studies have suggested that cyclin D1 levels are maintained at steady state by phosphorylation-dependent nuclear export and subsequent proteolysis in the cytoplasm. Here we present the crystal structures of the Skp1-FBXO31 complex alone and bound to a phosphorylated cyclin D1 C-terminal peptide. FBXO31 possesses a unique substrate-binding domain consisting of two β-barrel motifs, whereas cyclin D1 binds to FBXO31 by tucking its free C-terminal carboxylate tail into an open cavity of the C-terminal FBXO31 β-barrel. Biophysical and functional studies demonstrate that SCFFBXO31 is capable of recruiting and ubiquitinating cyclin D1 in a phosphorylation-independent manner. Our findings provide a conceptual framework for understanding the substrate specificity of the F-box protein FBXO31 and the mechanism of FBXO31-regulated cyclin D1 protein turnover.}, } @article {pmid29279381, year = {2018}, author = {Vitasse, Y and Signarbieux, C and Fu, YH}, title = {Global warming leads to more uniform spring phenology across elevations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1004-1008}, pmid = {29279381}, issn = {1091-6490}, mesh = {*Altitude ; Ecosystem ; Forests ; *Global Warming ; Models, Biological ; Plant Leaves/*growth & development/*physiology ; *Seasons ; Switzerland ; Temperature ; Trees/*growth & development/*physiology ; }, abstract = {One hundred years ago, Andrew D. Hopkins estimated the progressive delay in tree leaf-out with increasing latitude, longitude, and elevation, referred to as "Hopkins' bioclimatic law." What if global warming is altering this well-known law? Here, based on ∼20,000 observations of the leaf-out date of four common temperate tree species located in 128 sites at various elevations in the European Alps, we found that the elevation-induced phenological shift (EPS) has significantly declined from 34 d⋅1,000 m-1 conforming to Hopkins' bioclimatic law in 1960, to 22 d⋅1,000 m-1 in 2016, i.e., -35%. The stronger phenological advance at higher elevations, responsible for the reduction in EPS, is most likely to be connected to stronger warming during late spring as well as to warmer winter temperatures. Indeed, under similar spring temperatures, we found that the EPS was substantially reduced in years when the previous winter was warmer. Our results provide empirical evidence for a declining EPS over the last six decades. Future climate warming may further reduce the EPS with consequences for the structure and function of mountain forest ecosystems, in particular through changes in plant-animal interactions, but the actual impact of such ongoing change is today largely unknown.}, } @article {pmid29279380, year = {2018}, author = {Cheng, A and Zhao, T and Tse, KH and Chow, HM and Cui, Y and Jiang, L and Du, S and Loy, MMT and Herrup, K}, title = {ATM and ATR play complementary roles in the behavior of excitatory and inhibitory vesicle populations.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E292-E301}, pmid = {29279380}, issn = {1091-6490}, mesh = {Animals ; Ataxia Telangiectasia Mutated Proteins/genetics/metabolism ; Cells, Cultured ; Gene Expression Regulation ; Mice ; Mice, Knockout ; Neurons/*physiology ; Synapses/physiology ; Transport Vesicles/*physiology ; Vesicle-Associated Membrane Protein 2 ; }, abstract = {ATM (ataxia-telangiectasia mutated) and ATR (ATM and Rad3-related) are large PI3 kinases whose human mutations result in complex syndromes that include a compromised DNA damage response (DDR) and prominent nervous system phenotypes. Both proteins are nuclear-localized in keeping with their DDR functions, yet both are also found in cytoplasm, including on neuronal synaptic vesicles. In ATM- or ATR-deficient neurons, spontaneous vesicle release is reduced, but a drop in ATM or ATR level also slows FM4-64 dye uptake. In keeping with this, both proteins bind to AP-2 complex components as well as to clathrin, suggesting roles in endocytosis and vesicle recycling. The two proteins play complementary roles in the DDR; ATM is engaged in the repair of double-strand breaks, while ATR deals mainly with single-strand damage. Unexpectedly, this complementarity extends to these proteins' synaptic function as well. Superresolution microscopy and coimmunoprecipitation reveal that ATM associates exclusively with excitatory (VGLUT1+) vesicles, while ATR associates only with inhibitory (VGAT+) vesicles. The levels of ATM and ATR respond to each other; when ATM is deficient, ATR levels rise, and vice versa. Finally, blocking NMDA, but not GABA, receptors causes ATM levels to rise while ATR levels respond to GABA, but not NMDA, receptor blockade. Taken together, our data suggest that ATM and ATR are part of the cellular "infrastructure" that maintains the excitatory/inhibitory balance of the nervous system. This idea has important implications for the human diseases resulting from their genetic deficiency.}, } @article {pmid29279379, year = {2018}, author = {Wrangham, RW}, title = {Two types of aggression in human evolution.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {245-253}, pmid = {29279379}, issn = {1091-6490}, mesh = {Adaptation, Physiological/physiology ; Aggression/physiology/*psychology ; Biological Evolution ; *Competitive Behavior ; Female ; Humans ; Male ; Neural Pathways/physiology ; Reward ; *Social Behavior ; Violence/*psychology ; }, abstract = {Two major types of aggression, proactive and reactive, are associated with contrasting expression, eliciting factors, neural pathways, development, and function. The distinction is useful for understanding the nature and evolution of human aggression. Compared with many primates, humans have a high propensity for proactive aggression, a trait shared with chimpanzees but not bonobos. By contrast, humans have a low propensity for reactive aggression compared with chimpanzees, and in this respect humans are more bonobo-like. The bimodal classification of human aggression helps solve two important puzzles. First, a long-standing debate about the significance of aggression in human nature is misconceived, because both positions are partly correct. The Hobbes-Huxley position rightly recognizes the high potential for proactive violence, while the Rousseau-Kropotkin position correctly notes the low frequency of reactive aggression. Second, the occurrence of two major types of human aggression solves the execution paradox, concerned with the hypothesized effects of capital punishment on self-domestication in the Pleistocene. The puzzle is that the propensity for aggressive behavior was supposedly reduced as a result of being selected against by capital punishment, but capital punishment is itself an aggressive behavior. Since the aggression used by executioners is proactive, the execution paradox is solved to the extent that the aggressive behavior of which victims were accused was frequently reactive, as has been reported. Both types of killing are important in humans, although proactive killing appears to be typically more frequent in war. The biology of proactive aggression is less well known and merits increased attention.}, } @article {pmid29279378, year = {2018}, author = {Ahmed, F}, title = {Q&As with Marsha I. Lester.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {831-832}, pmid = {29279378}, issn = {1091-6490}, } @article {pmid29279377, year = {2018}, author = {Chen, B and Jiang, L and Zhong, ML and Li, JF and Li, BS and Peng, LJ and Dai, YT and Cui, BW and Yan, TQ and Zhang, WN and Weng, XQ and Xie, YY and Lu, J and Ren, RB and Chen, SN and Hu, JD and Wu, DP and Chen, Z and Tang, JY and Huang, JY and Mi, JQ and Chen, SJ}, title = {Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {373-378}, pmid = {29279377}, issn = {1091-6490}, mesh = {Adult ; Child ; Cohort Studies ; Gene Expression Profiling/methods ; *Gene Expression Regulation, Leukemic ; Gene Ontology ; HEK293 Cells ; Humans ; Jurkat Cells ; Kaplan-Meier Estimate ; Mutation ; Oncogene Proteins, Fusion/*genetics ; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma/*genetics ; *Transcriptome ; }, abstract = {T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1, TRA-SALL2, and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates >3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1, which predicted a poor prognosis in the adult group. Up-regulation of HOXA, MEF2C, and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.}, } @article {pmid29279376, year = {2018}, author = {Mets, DG and Brainard, MS}, title = {Genetic variation interacts with experience to determine interindividual differences in learned song.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {421-426}, pmid = {29279376}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Acoustic Stimulation/methods ; Animals ; Finches/genetics/*physiology ; *Genetic Variation ; Learning/*physiology ; Male ; Sound Spectrography/methods ; Vocalization, Animal/*physiology ; }, abstract = {Learning reflects the influence of experience on genetically determined circuitry, but little is known about how experience and genetics interact to determine complex learned phenotypes. Here, we used vocal learning in songbirds to study how experience and genetics contribute to interindividual differences in learned song. Previous work has established that such differences in song within a species depend on learning, but in principle some of these differences could also depend on genetic variation. We focused on song tempo, a learned and quantifiable feature that is controlled by central neural circuitry. To identify genetic contributions to tempo we computer-tutored juvenile Bengalese finches (Lonchura striata domestica) from different genetic backgrounds with synthetic songs in which tempo was systematically varied. Computer-tutored birds exhibited unexpectedly strong heritability for song tempo and comparatively weak influence of experience. We then tested whether heritability was fixed and independent of experience by providing a second group of birds with enriched instruction via live social tutoring. Live tutoring resulted in not only a significant increase in the influence of experience on tempo but also a dramatic decrease in the influence of genetics, indicating that enriched instruction could overcome genetic biases evident under computer tutoring. Our results reveal strong heritable genetic contributions to interindividual variation in song tempo but that the degree of heritability depends profoundly on the quality of instruction. They suggest that for more complex learned phenotypes, where it can be difficult to identify and control relevant experiential variables, heritability may similarly be contingent on the specifics of experience.}, } @article {pmid29279375, year = {2018}, author = {Carrington, LB and Tran, BCN and Le, NTH and Luong, TTH and Nguyen, TT and Nguyen, PT and Nguyen, CVV and Nguyen, HTC and Vu, TT and Vo, LT and Le, DT and Vu, NT and Nguyen, GT and Luu, HQ and Dang, AD and Hurst, TP and O'Neill, SL and Tran, VT and Kien, DTH and Nguyen, NM and Wolbers, M and Wills, B and Simmons, CP}, title = {Field- and clinically derived estimates of Wolbachia-mediated blocking of dengue virus transmission potential in Aedes aegypti mosquitoes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {361-366}, pmid = {29279375}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Aedes/microbiology/*virology ; Animals ; Dengue/blood/transmission/*virology ; Dengue Virus/*physiology ; Humans ; Logistic Models ; Mosquito Vectors/microbiology/*virology ; Pest Control, Biological/methods ; Time Factors ; Viremia/blood/virology ; Wolbachia/*physiology ; }, abstract = {The wMel strain of Wolbachia can reduce the permissiveness of Aedes aegypti mosquitoes to disseminated arboviral infections. Here, we report that wMel-infected Ae. aegypti (Ho Chi Minh City background), when directly blood-fed on 141 viremic dengue patients, have lower dengue virus (DENV) transmission potential and have a longer extrinsic incubation period than their wild-type counterparts. The wMel-infected mosquitoes that are field-reared have even greater relative resistance to DENV infection when fed on patient-derived viremic blood meals. This is explained by an increased susceptibility of field-reared wild-type mosquitoes to infection than laboratory-reared counterparts. Collectively, these field- and clinically relevant findings support the continued careful field-testing of wMel introgression for the biocontrol of Ae. aegypti-born arboviruses.}, } @article {pmid29279374, year = {2018}, author = {Jun, G and Manning, A and Almeida, M and Zawistowski, M and Wood, AR and Teslovich, TM and Fuchsberger, C and Feng, S and Cingolani, P and Gaulton, KJ and Dyer, T and Blackwell, TW and Chen, H and Chines, PS and Choi, S and Churchhouse, C and Fontanillas, P and King, R and Lee, S and Lincoln, SE and Trubetskoy, V and DePristo, M and Fingerlin, T and Grossman, R and Grundstad, J and Heath, A and Kim, J and Kim, YJ and Laramie, J and Lee, J and Li, H and Liu, X and Livne, O and Locke, AE and Maller, J and Mazur, A and Morris, AP and Pollin, TI and Ragona, D and Reich, D and Rivas, MA and Scott, LJ and Sim, X and Tearle, RG and Teo, YY and Williams, AL and Zöllner, S and Curran, JE and Peralta, J and Akolkar, B and Bell, GI and Burtt, NP and Cox, NJ and Florez, JC and Hanis, CL and McKeon, C and Mohlke, KL and Seielstad, M and Wilson, JG and Atzmon, G and Below, JE and Dupuis, J and Nicolae, DL and Lehman, D and Park, T and Won, S and Sladek, R and Altshuler, D and McCarthy, MI and Duggirala, R and Boehnke, M and Frayling, TM and Abecasis, GR and Blangero, J}, title = {Evaluating the contribution of rare variants to type 2 diabetes and related traits using pedigrees.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {379-384}, pmid = {29279374}, issn = {1091-6490}, support = {U01 DK085501/DK/NIDDK NIH HHS/United States ; R01 DK078616/DK/NIDDK NIH HHS/United States ; R01 HL113323/HL/NHLBI NIH HHS/United States ; 090532//Wellcome Trust/United Kingdom ; U01 DK085524/DK/NIDDK NIH HHS/United States ; U01 DK085545/DK/NIDDK NIH HHS/United States ; R01 DK098032/DK/NIDDK NIH HHS/United States ; //Department of Health/United Kingdom ; R01 DK047482/DK/NIDDK NIH HHS/United States ; U01 DK105535/DK/NIDDK NIH HHS/United States ; P30 DK098722/DK/NIDDK NIH HHS/United States ; U01 DK085526/DK/NIDDK NIH HHS/United States ; P30 DK020541/DK/NIDDK NIH HHS/United States ; 090367//Wellcome Trust/United Kingdom ; U01 DK085584/DK/NIDDK NIH HHS/United States ; U01 DK078616/DK/NIDDK NIH HHS/United States ; C06 RR020547/RR/NCRR NIH HHS/United States ; P30 DK020572/DK/NIDDK NIH HHS/United States ; //Wellcome Trust/United Kingdom ; 098381//Wellcome Trust/United Kingdom ; U54 GM115428/GM/NIGMS NIH HHS/United States ; G0601261//Medical Research Council/United Kingdom ; P30 DK020595/DK/NIDDK NIH HHS/United States ; R01 DK053889/DK/NIDDK NIH HHS/United States ; }, mesh = {Diabetes Mellitus, Type 2/ethnology/*genetics/pathology ; Family Health ; Female ; Gene Frequency ; Genetic Predisposition to Disease/ethnology/*genetics ; *Genetic Variation ; Genome-Wide Association Study/methods ; Genotype ; Humans ; Male ; Mexican Americans/*genetics ; Pedigree ; Phenotype ; Quantitative Trait Loci/genetics ; Whole Genome Sequencing/methods ; }, abstract = {A major challenge in evaluating the contribution of rare variants to complex disease is identifying enough copies of the rare alleles to permit informative statistical analysis. To investigate the contribution of rare variants to the risk of type 2 diabetes (T2D) and related traits, we performed deep whole-genome analysis of 1,034 members of 20 large Mexican-American families with high prevalence of T2D. If rare variants of large effect accounted for much of the diabetes risk in these families, our experiment was powered to detect association. Using gene expression data on 21,677 transcripts for 643 pedigree members, we identified evidence for large-effect rare-variant cis-expression quantitative trait loci that could not be detected in population studies, validating our approach. However, we did not identify any rare variants of large effect associated with T2D, or the related traits of fasting glucose and insulin, suggesting that large-effect rare variants account for only a modest fraction of the genetic risk of these traits in this sample of families. Reliable identification of large-effect rare variants will require larger samples of extended pedigrees or different study designs that further enrich for such variants.}, } @article {pmid29279373, year = {2018}, author = {Rangel, T and Rinn, A and Sharifzadeh, S and da Jornada, FH and Pick, A and Louie, SG and Witte, G and Kronik, L and Neaton, JB and Chatterjee, S}, title = {Low-lying excited states in crystalline perylene.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {284-289}, pmid = {29279373}, issn = {1091-6490}, abstract = {Organic materials are promising candidates for advanced optoelectronics and are used in light-emitting diodes and photovoltaics. However, the underlying mechanisms allowing the formation of excited states responsible for device functionality, such as exciton generation and charge separation, are insufficiently understood. This is partly due to the wide range of existing crystalline polymorphs depending on sample preparation conditions. Here, we determine the linear optical response of thin-film single-crystal perylene samples of distinct polymorphs in transmission and reflection geometries. The sample quality allows for unprecedented high-resolution spectroscopy, which offers an ideal opportunity for judicious comparison between theory and experiment. Excellent agreement with first-principles calculations for the absorption based on the GW plus Bethe-Salpeter equation (GW-BSE) approach of many-body perturbation theory (MBPT) is obtained, from which a clear picture of the low-lying excitations in perylene emerges, including evidence of an exciton-polariton stopband, as well as an assessment of the commonly used Tamm-Dancoff approximation to the GW-BSE approach. Our findings on this well-controlled system can guide understanding and development of advanced molecular solids and functionalization for applications.}, } @article {pmid29279372, year = {2018}, author = {Jansson, JO and Palsdottir, V and Hägg, DA and Schéle, E and Dickson, SL and Anesten, F and Bake, T and Montelius, M and Bellman, J and Johansson, ME and Cone, RD and Drucker, DJ and Wu, J and Aleksic, B and Törnqvist, AE and Sjögren, K and Gustafsson, JÅ and Windahl, SH and Ohlsson, C}, title = {Body weight homeostat that regulates fat mass independently of leptin in rats and mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {427-432}, pmid = {29279372}, issn = {1091-6490}, support = {P30 DK020572/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipose Tissue/*metabolism ; Animals ; Body Weight/*physiology ; Diet, High-Fat/adverse effects ; Energy Intake/drug effects/physiology ; Energy Metabolism/drug effects/physiology ; Gene Expression Regulation/drug effects ; Homeostasis/*drug effects/physiology ; Leptin/administration & dosage/*pharmacology ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Obese ; Obesity/etiology/genetics/*metabolism ; Osteocytes/metabolism ; Rats, Sprague-Dawley ; Weight Loss/drug effects/physiology ; }, abstract = {Subjects spending much time sitting have increased risk of obesity but the mechanism for the antiobesity effect of standing is unknown. We hypothesized that there is a homeostatic regulation of body weight. We demonstrate that increased loading of rodents, achieved using capsules with different weights implanted in the abdomen or s.c. on the back, reversibly decreases the biological body weight via reduced food intake. Importantly, loading relieves diet-induced obesity and improves glucose tolerance. The identified homeostat for body weight regulates body fat mass independently of fat-derived leptin, revealing two independent negative feedback systems for fat mass regulation. It is known that osteocytes can sense changes in bone strain. In this study, the body weight-reducing effect of increased loading was lost in mice depleted of osteocytes. We propose that increased body weight activates a sensor dependent on osteocytes of the weight-bearing bones. This induces an afferent signal, which reduces body weight. These findings demonstrate a leptin-independent body weight homeostat ("gravitostat") that regulates fat mass.}, } @article {pmid29279371, year = {2018}, author = {Soria, LR and Allegri, G and Melck, D and Pastore, N and Annunziata, P and Paris, D and Polishchuk, E and Nusco, E and Thöny, B and Motta, A and Häberle, J and Ballabio, A and Brunetti-Pierri, N}, title = {Enhancement of hepatic autophagy increases ureagenesis and protects against hyperammonemia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {391-396}, pmid = {29279371}, issn = {1091-6490}, mesh = {Ammonia/metabolism ; Animals ; *Autophagy ; Humans ; Hyperammonemia/*metabolism ; Liver/*metabolism ; Male ; Mechanistic Target of Rapamycin Complex 1/metabolism ; Mice, Inbred C57BL ; Mice, Knockout ; Mice, Transgenic ; Urea/*metabolism ; }, abstract = {Ammonia is a potent neurotoxin that is detoxified mainly by the urea cycle in the liver. Hyperammonemia is a common complication of a wide variety of both inherited and acquired liver diseases. If not treated early and thoroughly, it results in encephalopathy and death. Here, we found that hepatic autophagy is critically involved in systemic ammonia homeostasis by providing key urea-cycle intermediates and ATP. Hepatic autophagy is triggered in vivo by hyperammonemia through an α-ketoglutarate-dependent inhibition of the mammalian target of rapamycin complex 1, and deficiency of autophagy impairs ammonia detoxification. In contrast, autophagy enhancement by means of hepatic gene transfer of the master regulator of autophagy transcription factor EB or treatments with the autophagy enhancers rapamycin and Tat-Beclin-1 increased ureagenesis and protected against hyperammonemia in a variety of acute and chronic hyperammonemia animal models, including acute liver failure and ornithine transcarbamylase deficiency, the most frequent urea-cycle disorder. In conclusion, hepatic autophagy is an important mechanism for ammonia detoxification because of its support of urea synthesis, and its enhancement has potential for therapy of both primary and secondary causes of hyperammonemia.}, } @article {pmid29279370, year = {2018}, author = {Uhm, H and Kang, W and Ha, KS and Kang, C and Hohng, S}, title = {Single-molecule FRET studies on the cotranscriptional folding of a thiamine pyrophosphate riboswitch.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {331-336}, pmid = {29279370}, issn = {1091-6490}, mesh = {Aptamers, Nucleotide/chemistry/genetics/metabolism ; Base Sequence ; Escherichia coli/genetics/metabolism ; Fluorescence Resonance Energy Transfer ; Gene Expression Regulation, Bacterial ; Nucleic Acid Conformation ; *RNA Folding ; RNA, Bacterial/chemistry/genetics/metabolism ; *Riboswitch ; Thiamine Pyrophosphate/chemistry/*metabolism ; *Transcription, Genetic ; }, abstract = {Because RNAs fold as they are being synthesized, their transcription rate can affect their folding. Here, we report the results of single-molecule fluorescence studies that characterize the ligand-dependent cotranscriptional folding of the Escherichia coli thiM riboswitch that regulates translation. We found that the riboswitch aptamer folds into the "off" conformation independent of its ligand, but switches to the "on" conformation during transcriptional pausing near the translational start codon. Ligand binding maintains the riboswitch in the off conformation during transcriptional pauses. We expect our assay will permit the controlled study of the two main physical mechanisms that regulate cotranscriptional folding: transcriptional pausing and transcriptional speed.}, } @article {pmid29279369, year = {2018}, author = {Ridley, DA and Heald, CL and Ridley, KJ and Kroll, JH}, title = {Causes and consequences of decreasing atmospheric organic aerosol in the United States.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {290-295}, pmid = {29279369}, issn = {1091-6490}, mesh = {Aerosols/*analysis/chemistry ; Air Pollutants/*analysis ; Air Pollution/*analysis ; Carbon/chemistry ; Environmental Monitoring/legislation & jurisprudence/methods ; Fossil Fuels/analysis ; Geography ; Particulate Matter/*analysis ; United States ; United States Environmental Protection Agency/legislation & jurisprudence ; Vehicle Emissions/prevention & control ; }, abstract = {Exposure to atmospheric particulate matter (PM) exacerbates respiratory and cardiovascular conditions and is a leading source of premature mortality globally. Organic aerosol contributes a significant fraction of PM in the United States. Here, using surface observations between 1990 and 2012, we show that organic carbon has declined dramatically across the entire United States by 25-50%; accounting for more than 30% of the US-wide decline in PM. The decline is in contrast with the increasing organic aerosol due to wildfires and no clear trend in biogenic emissions. By developing a carbonaceous emissions database for the United States, we show that at least two-thirds of the decline in organic aerosol can be explained by changes in anthropogenic emissions, primarily from vehicle emissions and residential fuel burning. We estimate that the decrease in anthropogenic organic aerosol is responsible for averting 180,000 (117,000-389,000) premature deaths between 1990 and 2012. The unexpected decrease in organic aerosol, likely a consequence of the implementation of Clean Air Act Amendments, results in 84,000 (30,000-164,000) more lives saved than anticipated by the EPA between 2000 and 2010.}, } @article {pmid29279368, year = {2018}, author = {Kudalkar, SN and Beloor, J and Quijano, E and Spasov, KA and Lee, WG and Cisneros, JA and Saltzman, WM and Kumar, P and Jorgensen, WL and Anderson, KS}, title = {From in silico hit to long-acting late-stage preclinical candidate to combat HIV-1 infection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {E802-E811}, pmid = {29279368}, issn = {1091-6490}, support = {T32 GM007223/GM/NIGMS NIH HHS/United States ; UL1 TR001863/TR/NCATS NIH HHS/United States ; R21 AI122384/AI/NIAID NIH HHS/United States ; R01 AI044616/AI/NIAID NIH HHS/United States ; R33 AI122384/AI/NIAID NIH HHS/United States ; R01 AI112443/AI/NIAID NIH HHS/United States ; R01 EB000487/EB/NIBIB NIH HHS/United States ; R01 GM049551/GM/NIGMS NIH HHS/United States ; T32 GM007205/GM/NIGMS NIH HHS/United States ; R56 EB000487/EB/NIBIB NIH HHS/United States ; }, mesh = {Animals ; Anti-HIV Agents/*administration & dosage/pharmacokinetics ; Computer Simulation ; Disease Models, Animal ; *Drug Delivery Systems ; Drug Evaluation, Preclinical ; Drug Synergism ; HIV Infections/*drug therapy ; *HIV-1 ; Mice ; Mice, Inbred BALB C ; Nanoparticles ; }, abstract = {The HIV-1 pandemic affecting over 37 million people worldwide continues, with nearly one-half of the infected population on highly active antiretroviral therapy (HAART). Major therapeutic challenges remain because of the emergence of drug-resistant HIV-1 strains, limitations because of safety and toxicity with current HIV-1 drugs, and patient compliance for lifelong, daily treatment regimens. Nonnucleoside reverse transcriptase inhibitors (NNRTIs) that target the viral polymerase have been a key component of the current HIV-1 combination drug regimens; however, these issues hamper them. Thus, the development of novel more effective NNRTIs as anti-HIV-1 agents with fewer long-term liabilities, efficacy on new drug-resistant HIV-1 strains, and less frequent dosing is crucial. Using a computational and structure-based design strategy to guide lead optimization, a 5 µM virtual screening hit was transformed to a series of very potent nanomolar to picomolar catechol diethers. One representative, compound I, was shown to have nanomolar activity in HIV-1-infected T cells, potency on clinically relevant HIV-1 drug-resistant strains, lack of cytotoxicity and off-target effects, and excellent in vivo pharmacokinetic behavior. In this report, we show the feasibility of compound I as a late-stage preclinical candidate by establishing synergistic antiviral activity with existing HIV-1 drugs and clinical candidates and efficacy in HIV-1-infected humanized [human peripheral blood lymphocyte (Hu-PBL)] mice by completely suppressing viral loads and preventing human CD4+ T-cell loss. Moreover, a long-acting nanoformulation of compound I [compound I nanoparticle (compound I-NP)] in poly(lactide-coglycolide) (PLGA) was developed that shows sustained maintenance of plasma drug concentrations and drug efficacy for almost 3 weeks after a single dose.}, } @article {pmid29279367, year = {2018}, author = {Itoh, N and Itoh, Y and Tassoni, A and Ren, E and Kaito, M and Ohno, A and Ao, Y and Farkhondeh, V and Johnsonbaugh, H and Burda, J and Sofroniew, MV and Voskuhl, RR}, title = {Cell-specific and region-specific transcriptomics in the multiple sclerosis model: Focus on astrocytes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E302-E309}, pmid = {29279367}, issn = {1091-6490}, support = {R01 NS096748/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Astrocytes/*physiology ; Cholesterol/biosynthesis ; Down-Regulation ; Encephalomyelitis, Autoimmune, Experimental/*metabolism/pathology ; Gene Expression Regulation ; Homeostasis/physiology ; Mice ; Mice, Inbred C57BL ; Multiple Sclerosis/*pathology ; RNA, Messenger/genetics/metabolism ; Transcriptome/*physiology ; Up-Regulation ; }, abstract = {Changes in gene expression that occur across the central nervous system (CNS) during neurological diseases do not address the heterogeneity of cell types from one CNS region to another and are complicated by alterations in cellular composition during disease. Multiple sclerosis (MS) is multifocal by definition. Here, a cell-specific and region-specific transcriptomics approach was used to determine gene expression changes in astrocytes in the most widely used MS model, experimental autoimmune encephalomyelitis (EAE). Astrocyte-specific RNAs from various neuroanatomic regions were attained using RiboTag technology. Sequencing and bioinformatics analyses showed that EAE-induced gene expression changes differed between neuroanatomic regions when comparing astrocytes from spinal cord, cerebellum, cerebral cortex, and hippocampus. The top gene pathways that were changed in astrocytes from spinal cord during chronic EAE involved decreases in expression of cholesterol synthesis genes while immune pathway gene expression in astrocytes was increased. Optic nerve from EAE and optic chiasm from MS also showed decreased cholesterol synthesis gene expression. The potential role of cholesterol synthesized by astrocytes during EAE and MS is discussed. Together, this provides proof-of-concept that a cell-specific and region-specific gene expression approach can provide potential treatment targets in distinct neuroanatomic regions during multifocal neurological diseases.}, } @article {pmid29279296, year = {2018}, author = {Connolly, SR and Keith, SA and Colwell, RK and Rahbek, C}, title = {Mechanism, Process, and Causation in Ecological Models: A Reply to McGill and Potochnik.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {305-306}, doi = {10.1016/j.tree.2017.11.009}, pmid = {29279296}, issn = {1872-8383}, mesh = {*Causality ; *Models, Theoretical ; }, } @article {pmid29278721, year = {2018}, author = {Blom-Dahl, D and Azpiazu, N}, title = {The Pax protein Eyegone (Eyg) interacts with the pi-RNA component Aubergine (Aub) and controls egg chamber development in Drosophila.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {267-277}, doi = {10.1016/j.ydbio.2017.12.012}, pmid = {29278721}, issn = {1095-564X}, mesh = {Animals ; Cytoplasm/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Female ; Heterochromatin/genetics/metabolism ; Nuclear Proteins/genetics/metabolism ; Ovary/*metabolism ; Ovum/*metabolism ; Paxillin/genetics/metabolism ; Peptide Initiation Factors/genetics/*metabolism ; RNA, Messenger/genetics/metabolism ; RNA-Binding Proteins/genetics/metabolism ; Retroelements ; }, abstract = {The eyegone (eyg) gene encodes Eyg, a transcription factor of the Pax family with multiple roles during Drosophila development. Eyg has been shown to be nuclear in the cells where it functions. In this report we describe a new functional cytoplasmic distribution of Eyg during egg chamber development in the female ovarioles. The protein is present from the germarium until stage 10 of cyst development. The majority of egg chambers that develop in the absence of Eyg arrest their development before stage 10, show augmented levels of the telomeric retro-transposon TART-A and low levels of heterochromatin marks in the oocyte nucleus. During the maternal to zygotic transition (MTZ) Eyg seems to play a role in destabilizing germ cell less (gcl) and oo 16 RNA binding protein (orb) mRNAs. We were able to show that Eyg interacts with Aubergine (Aub), a component of the pi-RNA pathway during egg chamber development. This interaction could be essential for Eyg to be retained in the cytoplasm and fulfill its functions there.}, } @article {pmid29277542, year = {2018}, author = {Springer, MS and Gatesy, J}, title = {Evolution of the MC5R gene in placental mammals with evidence for its inactivation in multiple lineages that lack sebaceous glands.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {364-374}, doi = {10.1016/j.ympev.2017.12.010}, pmid = {29277542}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Databases, Genetic ; *Evolution, Molecular ; Female ; Mammals/classification/*metabolism ; Phylogeny ; Placenta/metabolism ; Pregnancy ; Receptors, Melanocortin/classification/*genetics ; Sebaceous Glands/*physiology ; Sequence Alignment ; }, abstract = {MC5R is one of five melanocortin receptor genes found in placental mammals. MC5R plays an important role in energy homeostasis and is also expressed in the terminal differentiation of sebaceous glands. Among placental mammals there are multiple lineages that either lack or have degenerative sebaceous glands including Cetacea (whales, dolphins, and porpoises), Hippopotamidae (hippopotamuses), Sirenia (manatees and dugongs), Proboscidea (elephants), Rhinocerotidae (rhinos), and Heterocephalus glaber (naked mole rat). Given the loss or diminution of sebaceous glands in these taxa, we procured MC5R sequences from publicly available genomes and transcriptomes, supplemented by a newly generated sequence for Choeropsis liberiensis (pygmy hippopotamus), to determine if this gene remains intact or is inactivated in association with loss/reduction of sebaceous glands. Our data set includes complete MC5R sequences for 114 placental mammal species including two individuals of Mammuthus primigenius (woolly mammoth) from Oimyakon and Wrangel Island. Complete loss or inactivation of the MC5R gene occurs in multiple placental lineages that have lost sebaceous glands (Cetacea, West Indian manatee, African elephant, white rhinoceros) or are characterized by unusual skin (pangolins, aardvarks). Both M. primigenius individuals share inactivating mutations with the African elephant even though sebaceous glands have been reported in the former. MC5R remains intact in hippopotamuses and the naked mole rat, although slightly elevated dN/dS ratios in these lineages allow for the possibility that the accumulation of inactivating mutations in MC5R may lag behind the relaxation of purifying selection. For Cetacea and Hippopotamidae, the absence of shared inactivating mutations in two different skin genes (MC5R, PSORS1C2) is consistent with the hypothesis that semi-aquatic lifestyles were acquired independently in these clades following divergence from a common ancestor.}, } @article {pmid29277455, year = {2018}, author = {Vitale, I and Galluzzi, L}, title = {Everybody In! No Bouncers at Tumor Gates.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {85-87}, doi = {10.1016/j.tig.2017.12.006}, pmid = {29277455}, issn = {0168-9525}, mesh = {DNA Repair ; Humans ; *Microsatellite Repeats ; Neoplasms/*genetics ; }, abstract = {Two recent genomic studies suggest that a large fraction of human tumors evolves in the presence of limited negative selection against somatic mutations. In this context, specific genetic defects enable the establishment of a hypermutant state that may constitute a target for immunotherapeutic interventions.}, } @article {pmid29277454, year = {2018}, author = {Darabi-Darestani, K and Sari, A and Sarafrazi, A and Utevsky, S}, title = {Entrapped by the uneven central and Middle Eastern terrains: Genetic status of populations of Hirudo orientalis (Annelida, Clitellata, Hirudinida) with a phylogenetic review of the genus Hirudo.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {52-60}, doi = {10.1016/j.ympev.2017.12.024}, pmid = {29277454}, issn = {1095-9513}, mesh = {Animal Migration ; Animals ; Annelida/*classification/*genetics ; Base Sequence ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Genetic Variation ; *Genetics, Population ; Geography ; Haplotypes/genetics ; Middle East ; *Phylogeny ; }, abstract = {Phylogenetic relationships between species of the genus Hirudo plus genetic variation in the entire distribution range of Hirudo orientalis were investigated based on mitochondrial (COI and 12S rDNA) and nuclear (ITS1+5.8S+ITS2) genome regions. The sister relationship of Hirudo orientalis and H. medicinalis was revealed with a high posterior probability. A broad and patchy distribution with minor genetic differences was observed in populations of H. orientalis along the central and Middle Eastern parts of Asia. The known distribution range occurred in topographically heterogeneous landscapes around the Caspian Sea. The demographic analysis suggests the selection of the COI locus under unfavourable respiratory conditions, but population size expansion cannot be fully rejected. The genetic variation trend indicated northward dispersal. Higher haplotype diversity in the South Caspian region potentially suggests the area as a historical refugium for the species. The vast dispersal is assumed to occur after the Pleistocene glaciations via vertebrate hosts.}, } @article {pmid29277278, year = {2018}, author = {Kuparinen, A and Uusi-Heikkilä, S}, title = {Sustainability of Fishing Is about Abundance: A Response to Bernatchez et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {307-308}, doi = {10.1016/j.tree.2017.12.003}, pmid = {29277278}, issn = {1872-8383}, mesh = {*Conservation of Natural Resources ; *Fisheries ; Fishes ; }, } @article {pmid29277086, year = {2018}, author = {Hagström, E and Andersson, SG}, title = {The challenges of integrating two genomes in one cell.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {89-94}, doi = {10.1016/j.mib.2017.12.003}, pmid = {29277086}, issn = {1879-0364}, mesh = {Bacteria/*genetics/metabolism/pathogenicity ; Cell Nucleus/genetics ; *Evolution, Molecular ; *Genome ; Genome, Mitochondrial ; Humans ; Mitochondria/*genetics ; Oxygen/metabolism ; Phylogeny ; Respiration ; Symbiosis/genetics ; }, abstract = {Mutualistic bacteria and mitochondria have small genomes that harbor host-essential genes. A major question is why a distinct bacterial or mitochondrial genome is needed to encode these functions. The dual location of genes demand two sets of information processing systems, coordination of gene expression and elaborate transport systems. A simpler solution would be to harbor all genes in a single genome. Functional gene transfers to the host nuclear genome is uncommon in mutualistic bacteria and lost gene functions are rather rescued by co-symbiotic bacteria. Recent findings suggest that the mitochondrial genome is retained to avoid conflicting signals between protein targeting pathways in the cell. However, if the selective pressure for oxygenic respiration is lost, the mitochondrial genome will start to deteriorate and soon be lost.}, } @article {pmid29276074, year = {2018}, author = {Grevelding, CG and Langner, S and Dissous, C}, title = {Kinases: Molecular Stage Directors for Schistosome Development and Differentiation.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {246-260}, doi = {10.1016/j.pt.2017.12.001}, pmid = {29276074}, issn = {1471-5007}, support = {107475/Z/15/Z//Wellcome Trust/United Kingdom ; }, mesh = {Animals ; Female ; Humans ; Male ; Protein Kinases/*metabolism ; Schistosoma/*enzymology/*growth & development ; Schistosomiasis/*parasitology ; }, abstract = {Understanding schistosome biology is still a challenging mission. The reproductive biology of this parasitic trematode is closely associated with the pathologic consequences of schistosomiasis, the devastating infectious disease caused by members of the family Schistosomatidae worldwide. Recent studies of signaling mechanisms confirmed the prominent roles of protein kinases (PKs) in directing schistosome biology, and first evidence was obtained for an additional contribution of kinases with substrates different from proteins (non-PKs). This review provides an overview of the Schistosoma mansoni kinome in the context of male-female interaction and summarizes recent studies of kinases controlling development and differentiation. Due to their importance for schistosome biology, kinases represent Achilles' heels and are therefore of high value also for translational research.}, } @article {pmid29275982, year = {2018}, author = {McGill, BJ and Potochnik, A}, title = {Mechanisms Are Causes, Not Components: A Response to Connolly et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {5}, pages = {304-305}, doi = {10.1016/j.tree.2017.11.010}, pmid = {29275982}, issn = {1872-8383}, } @article {pmid29275009, year = {2018}, author = {Morley, NJ}, title = {Paramphistomosis of Ruminants: The Role of Free-Living Metacercariae.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {97-98}, doi = {10.1016/j.pt.2017.10.005}, pmid = {29275009}, issn = {1471-5007}, mesh = {Animals ; Fasciola hepatica ; Fascioliasis ; Humans ; *Metacercariae ; Ruminants ; *Trematode Infections ; }, } @article {pmid29275008, year = {2018}, author = {Huson, KM and Oliver, NAM and Robinson, MW}, title = {Response to Morley: The Influence of Climate on Survival of Paramphistome Metacercariae.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {98-99}, doi = {10.1016/j.pt.2017.10.006}, pmid = {29275008}, issn = {1471-5007}, mesh = {Animals ; *Climate ; *Metacercariae ; }, } @article {pmid29275007, year = {2018}, author = {Pollastri, MP}, title = {Fexinidazole: A New Drug for African Sleeping Sickness on the Horizon.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {178-179}, pmid = {29275007}, issn = {1471-5007}, support = {R01 AI114685/AI/NIAID NIH HHS/United States ; R01 AI124046/AI/NIAID NIH HHS/United States ; R21 AI127594/AI/NIAID NIH HHS/United States ; }, mesh = {Clinical Trials as Topic ; Drug Approval ; Humans ; Nitroimidazoles/*therapeutic use ; Trypanocidal Agents/*therapeutic use ; *Trypanosoma brucei gambiense ; Trypanosomiasis, African/*drug therapy ; }, abstract = {Decades after the last new chemical entity was added to the pharmacopeia for human African trypanosomiasis (or sleeping sickness), orally dosed fexinidazole stands poised to replace the current treatment regimen for Trypanosoma brucei gambiense infections, following a positive Phase 2/3 clinical trial.}, } @article {pmid29274739, year = {2018}, author = {Martin, MD and Quiroz-Claros, E and Brush, GS and Zimmer, EA}, title = {Herbarium collection-based phylogenetics of the ragweeds (Ambrosia, Asteraceae).}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {335-341}, doi = {10.1016/j.ympev.2017.12.023}, pmid = {29274739}, issn = {1095-9513}, mesh = {Ambrosia/*classification/genetics ; Bayes Theorem ; DNA, Chloroplast/classification/genetics ; DNA, Plant/chemistry/isolation & purification/metabolism ; Evolution, Molecular ; Genetic Variation ; Hybridization, Genetic ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Ambrosia (Asteraceae) is a taxonomically difficult genus of weedy, wind-pollinated plants with an apparent center of diversity in the Sonoran Desert of North America. Determining Ambrosia's evolutionary relationships has been the subject of much interest, with numerous studies using morphological characters, cytology, comparative phytochemistry, and chloroplast restriction site variation to produce conflicting accounts the relationships between Ambrosia species, as well as the classification of their close relatives in Franseria and Hymenoclea. To resolve undetermined intra-generic relationships within Ambrosia, we used DNA extracted from tissues obtained from seed banks and herbarium collections to generate multi-locus genetic data representing nearly all putative species, including four from South America. We performed Bayesian and Maximum-Likelihood phylogenetic analyses of six chloroplast-genome and two nuclear-genome markers, enabling us to infer monophyly for the genus, resolve major infra-generic species clusters, as well as to resolve open questions about the evolutionary relationships of several Ambrosia species and former members of Franseria. We also provide molecular data supporting the hypothesis that A. sandersonii formed through the hybridization of A. eriocentra and A. salsola. The topology of our chloroplast DNA phylogeny is almost entirely congruent with the most recent molecular work based on chloroplast restriction site variation of a much more limited sampling of 14 North American species of Ambrosia, although our improved sampling of global Ambrosia diversity enables us to draw additional conclusions. As our study is the first direct DNA sequence-based phylogenetic analyses of Ambrosia, we analyze the data in relation to previous taxonomic studies and discuss several instances of chloroplast/nuclear incongruence that leave the precise geographic center of origin of Ambrosia in question.}, } @article {pmid29274664, year = {2018}, author = {Doherty, TS and Driscoll, DA}, title = {Competition in the Historical Niche: A Response to Scheele et al.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {147-148}, doi = {10.1016/j.tree.2017.12.004}, pmid = {29274664}, issn = {1872-8383}, mesh = {*Ecosystem ; }, } @article {pmid29274498, year = {2018}, author = {Kajtoch, Ł and Montagna, M and Wanat, M}, title = {Species delimitation within the Bothryorrhynchapion weevils: Multiple evidence from genetics, morphology and ecological associations.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {354-363}, doi = {10.1016/j.ympev.2017.12.022}, pmid = {29274498}, issn = {1095-9513}, mesh = {Animals ; DNA/chemistry/isolation & purification/metabolism ; Electron Transport Complex IV/classification/genetics ; Female ; Genetic Variation ; Male ; Peptide Elongation Factor 1/classification/genetics ; Phylogeny ; Sequence Analysis, DNA ; Weevils/*classification/genetics/parasitology ; Wolbachia/genetics/physiology ; }, abstract = {Curculionidae is a hyperdiverse group of beetles, whose taxonomy and phylogenetics are still poorly understood, especially at the genus level. The latest work on the evolution of Apionini showed a noticeable "mess" in the subtribe Oxystomatina, where most of the morphology-based genera were found to be polyphyletic or paraphyletic. These discrepancies between classical taxonomy and molecular phylogenetics implied the need for further taxonomic revision of these groups. Here, we used sets of morphological, molecular and ecological characters to verify the taxonomic statuses and disentangle the phylogenetic relations among the Bothryorrhynchapion apionids, which are classified as a subgenus of Cyanapion. Morphological data including morphometrics, and multilocus molecular analyses confirmed the monophyly of the Bothryorrhynchapion and species statuses of five species. The morphological analyses showed that Cyanapion (Bothryorrhynchapion) protractum (Sharp, 1891) from the southeast Palaearctic is a synonym of C. (B.) gyllenhalii (Kirby). Moreover, ecological features (host plant use and presence/absence of the endosymbiotic bacteria Wolbachia) helped to unravel the relations among the examined weevils. The speciation of Bothryorrhynchapion apionids was probably affected by allopatric distribution, shifts in the preferred host plants (Vicia sp. or Lathyrus sp.) of sympatric taxa, and infection by different strains of Wolbachia. The paper presents the first comprehensive description of the species' morphology, biology and ecology, and includes a key to the species.}, } @article {pmid29274497, year = {2018}, author = {Scott Chialvo, CH and Chialvo, P and Holland, JD and Anderson, TJ and Breinholt, JW and Kawahara, AY and Zhou, X and Liu, S and Zaspel, JM}, title = {A phylogenomic analysis of lichen-feeding tiger moths uncovers evolutionary origins of host chemical sequestration.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {23-34}, pmid = {29274497}, issn = {1095-9513}, support = {R01 GM098856/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Evolution, Molecular ; *Genomics ; Lichens/*physiology ; Metabolic Networks and Pathways ; Metabolomics ; Moths/*classification/*genetics ; Phenols/chemistry/metabolism ; *Phylogeny ; Species Specificity ; Statistics as Topic ; }, abstract = {Host species utilize a variety of defenses to deter feeding, including secondary chemicals. Some phytophagous insects have evolved tolerance to these chemical defenses, and can sequester secondary defense compounds for use against their own predators and parasitoids. While numerous studies have examined plant-insect interactions, little is known about lichen-insect interactions. Our study focused on reconstructing the evolution of lichen phenolic sequestration in the tiger moth tribe Lithosiini (Lepidoptera: Erebidae: Arctiinae), the most diverse lineage of lichen-feeding moths, with 3000 described species. We built an RNA-Seq dataset and examined the adult metabolome for the presence of lichen-derived phenolics. Using the transcriptomic dataset, we recover a well-resolved phylogeny of the Lithosiini, and determine that the metabolomes within species are more similar than those among species. Results from an initial ancestral state reconstruction suggest that the ability to sequester phenolics produced by a single chemical pathway preceded generalist sequestration of phenolics produced by multiple chemical pathways. We conclude that phenolics are consistently and selectively sequestered within Lithosiini. Furthermore, sequestration of compounds from a single chemical pathway may represent a synapomorphy of the tribe, and the ability to sequester phenolics produced by multiple pathways arose later. These findings expand on our understanding of the interactions between Lepidoptera and their lichen hosts.}, } @article {pmid29274496, year = {2018}, author = {Paladini, A and Takiya, DM and Urban, JM and Cryan, JR}, title = {New World spittlebugs (Hemiptera: Cercopidae: Ischnorhininae): Dated molecular phylogeny, classification, and evolution of aposematic coloration.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {321-334}, doi = {10.1016/j.ympev.2017.12.020}, pmid = {29274496}, issn = {1095-9513}, mesh = {Animals ; Biodiversity ; Electron Transport Complex IV/classification/genetics/metabolism ; *Evolution, Molecular ; Fossils ; Hemiptera/*classification/genetics ; Histones/classification/genetics/metabolism ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 18S/chemistry/classification/genetics ; }, abstract = {The spittlebug family Cercopidae (Hemiptera: Auchenorrhyncha: Cicadomorpha: Cercopoidea) is distributed worldwide, with highest species diversity in the tropics. Several included species are economically important pests of major agricultural crops and cultivated pasture grasses. Taxonomically, Cercopidae is divided into two subfamilies: the paraphyletic Old World Cercopinae and the monophyletic New World Ischnorhininae. Results are here presented from an investigation of phylogenetic relationships within Ischnorhininae based on DNA sequences from seven loci (18S rDNA, 28S rDNA, Histone 2A, Histone 3, Wingless, Cytochrome Oxidase I, and Cytochrome Oxidase II) generated from exemplars of 119 spittlebug species. The resulting topology is used to test alternative higher-level classification hypotheses of Ischnorhininae and, with fossil-calibration, dates were estimated for major events in the evolutionary history of Cercopidae, including a much earlier divergence date (around 68-50 Mya) than previously reported in the literature. In addition, for the first time in Cercopidae, ancestral states of some predation avoidances strategies were reconstructed, with results suggesting an origin of aposematic coloration in the Cercopidae ancestor, with subsequent independent losses of aposematic coloration in multiple lineages.}, } @article {pmid29274495, year = {2018}, author = {Huang, XC and Wu, RW and An, CT and Xie, GL and Su, JH and Ouyang, S and Zhou, CH and Wu, XP}, title = {Reclassification of Lamprotula rochechouartii as Margaritifera rochechouartiicomb. nov. (Bivalvia: Margaritiferidae) revealed by time-calibrated multi-locus phylogenetic analyses and mitochondrial phylogenomics of Unionoida.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {297-306}, doi = {10.1016/j.ympev.2017.12.017}, pmid = {29274495}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Bivalvia/*classification/*genetics ; DNA, Mitochondrial/chemistry/isolation & purification/metabolism ; Electron Transport Complex IV/chemistry/classification/genetics ; Fossils ; Genome, Mitochondrial/*genetics ; Haplotypes ; *Phylogeny ; Phylogeography ; RNA, Ribosomal, 16S/chemistry/classification/genetics ; }, abstract = {The family Margaritiferidae encompasses 12 valid species, which are distributed widely but disjunctively in the Northern Hemisphere. A lack of a well resolved and temporally calibrated phylogenetic framework of Margaritiferidae has made it difficult to discuss the evolutionary pattern and process. Phylogenetic relationships between five major clades, which were revealed in earlier studies, remain elusive and unresolved. Lamprotula rochechouartii has long been classified within the family Unionidae based on shell morphology, but our preliminary molecular study on this species made us hypothesize that it has an affinity with margaritiferids. Hence, five loci (COI, 16S, 18S, 28S and histone H3) were used to investigate the phylogenetic position of L. rochechouartii and intra-familial relationships within Margaritiferidae using various partitioning strategies. Moreover, two mitochondrial genomes were newly obtained to further resolve and validate the five-clade relationships within Margaritiferidae in a broad view of Unionoida evolution. Both five-gene and mitogenome datasets strongly advocated treating Lamprotula rochechouartii as Margaritifera rochechouartiicomb. nov. Maximum likelihood and Bayesian inference analyses using partitioned five-gene dataset resulted in various topologies, but five well-supported clades were obtained. The most probable cladistic relationships generated by five-gene dataset analyses were identical to subsequent whole mitogenome analyses except the position of M. monodonta. M. rochechouartii and M. laosensis had a well-supported sister relationship and formed a basal clade splitting from the rest of the family. Based on six reliable fossils, crown age of the extant Margaritiferidae was estimated during the Late Cretaceous at 88.3 Ma (95% HPD = 66.2-117.4). But we hypothesized a much earlier origin of this family due to the Permian stem age (mean = 257 Ma, 95% HPD = 230.0-296.0) and a high extinction rate in the whole order. Biogeographic scenarios supported a Laurasian origin of extant Margaritiferidae during the Late Cretaceous, and suggested that Asian margaritiferids may have had two origins, having either Asia (M. rochechouartii, M. laosensis) or North America (M. dahurica, M. laevis, and M. middendorffi) as ancestral. The newly added Margaritiferidae species M. rochechouartii expands our recognized distribution range of modern margaritiferids. Our results indicate that whole mitogenome sequences can be used to reconstruct robust phylogenetic relationships for freshwater mussels, especially with the help of adding M-type mitogenomes.}, } @article {pmid29274320, year = {2018}, author = {Firmani, LD and Uliasz, TF and Mehlmann, LM}, title = {The switch from cAMP-independent to cAMP-dependent arrest of meiotic prophase is associated with coordinated GPR3 and CDK1 expression in mouse oocytes.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {196-205}, doi = {10.1016/j.ydbio.2017.12.014}, pmid = {29274320}, issn = {1095-564X}, mesh = {Animals ; CDC2 Protein Kinase/*biosynthesis/genetics ; Cell Cycle Checkpoints/*physiology ; Cyclic AMP/genetics/*metabolism ; Female ; Gene Expression Regulation/*physiology ; Meiotic Prophase I/*physiology ; Mice ; Mice, Knockout ; Oocytes/cytology/*metabolism ; Receptors, G-Protein-Coupled/*biosynthesis/genetics ; Second Messenger Systems/*physiology ; }, abstract = {Mammalian oocytes are arrested in meiotic prophase from around the time of birth until just before ovulation. Following an extended period of growth, they are stimulated to mature to the metaphase II stage by a preovulatory luteinizing hormone (LH) surge that occurs with each reproductive cycle. Small, growing oocytes are not competent to mature into fertilizable eggs because they do not possess adequate amounts of cell cycle regulatory proteins, particularly cyclin-dependent kinase 1 (CDK1). As oocytes grow, they synthesize CDK1 and acquire the ability to mature. After oocytes achieve meiotic competence, meiotic arrest at the prophase stage is dependent on high levels of cAMP that are generated in the oocyte under the control of the constitutively active Gs-coupled receptor, GPR3. In this study, we examined the switch between GPR3-independent and GPR3-dependent meiotic arrest. We found that the ability of oocytes to mature, as well as oocyte CDK1 levels, were dependent on follicle size, but CDK1 expression in oocytes from preantral follicles was not acutely altered by the activity of follicle stimulating hormone (FSH). Gpr3 was expressed and active in incompetent oocytes within early stage follicles, well before cAMP is required to maintain meiotic arrest. Oocytes from Gpr3-/- mice were less competent to mature than oocytes from Gpr3+/+ mice, as assessed by the time course of germinal vesicle breakdown. Correspondingly, Gpr3-/- oocytes contained significantly lower CDK1 levels than their Gpr3+/+ counterparts that were at the same stage of follicle development. These results demonstrate that GPR3 potentiates meiotic competence, most likely by raising cAMP.}, } @article {pmid29274113, year = {2018}, author = {Simonet, C and Scherrer, R and Rego-Costa, A and Etienne, RS}, title = {Robustness of the approximate likelihood of the protracted speciation model.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {469-479}, doi = {10.1111/jeb.13233}, pmid = {29274113}, issn = {1420-9101}, abstract = {The protracted speciation model presents a realistic and parsimonious explanation for the observed slowdown in lineage accumulation through time, by accounting for the fact that speciation takes time. A method to compute the likelihood for this model given a phylogeny is available and allows estimation of its parameters (rate of initiation of speciation, rate of completion of speciation and extinction rate) and statistical comparison of this model to other proposed models of diversification. However, this likelihood computation method makes an approximation of the protracted speciation model to be mathematically tractable: it sometimes counts fewer species than one would do from a biological perspective. This approximation may have large consequences for likelihood-based inferences: it may render any conclusions based on this method completely irrelevant. Here, we study to what extent this approximation affects parameter estimations. We simulated phylogenies from which we reconstructed the tree of extant species according to the original, biologically meaningful protracted speciation model and according to the approximation. We then compared the resulting parameter estimates. We found that the differences were larger for high values of extinction rates and small values of speciation-completion rates. Indeed, a long speciation-completion time and a high extinction rate promote the appearance of cases to which the approximation applies. However, surprisingly, the deviation introduced is largely negligible over the parameter space explored, suggesting that this approximate likelihood can be applied reliably in practice to estimate biologically relevant parameters under the original protracted speciation model.}, } @article {pmid29273807, year = {2018}, author = {Turcot, V and Lu, Y and Highland, HM and Schurmann, C and Justice, AE and Fine, RS and Bradfield, JP and Esko, T and Giri, A and Graff, M and Guo, X and Hendricks, AE and Karaderi, T and Lempradl, A and Locke, AE and Mahajan, A and Marouli, E and Sivapalaratnam, S and Young, KL and Alfred, T and Feitosa, MF and Masca, NGD and Manning, AK and Medina-Gomez, C and Mudgal, P and Ng, MCY and Reiner, AP and Vedantam, S and Willems, SM and Winkler, TW and Abecasis, G and Aben, KK and Alam, DS and Alharthi, SE and Allison, M and Amouyel, P and Asselbergs, FW and Auer, PL and Balkau, B and Bang, LE and Barroso, I and Bastarache, L and Benn, M and Bergmann, S and Bielak, LF and Blüher, M and Boehnke, M and Boeing, H and Boerwinkle, E and Böger, CA and Bork-Jensen, J and Bots, ML and Bottinger, EP and Bowden, DW and Brandslund, I and Breen, G and Brilliant, MH and Broer, L and Brumat, M and Burt, AA and Butterworth, AS and Campbell, PT and Cappellani, S and Carey, DJ and Catamo, E and Caulfield, MJ and Chambers, JC and Chasman, DI and Chen, YI and Chowdhury, R and Christensen, C and Chu, AY and Cocca, M and Collins, FS and Cook, JP and Corley, J and Corominas Galbany, J and Cox, AJ and Crosslin, DS and Cuellar-Partida, G and D'Eustacchio, A and Danesh, J and Davies, G and Bakker, PIW and Groot, MCH and Mutsert, R and Deary, IJ and Dedoussis, G and Demerath, EW and Heijer, M and Hollander, AI and Ruijter, HM and Dennis, JG and Denny, JC and Di Angelantonio, E and Drenos, F and Du, M and Dubé, MP and Dunning, AM and Easton, DF and Edwards, TL and Ellinghaus, D and Ellinor, PT and Elliott, P and Evangelou, E and Farmaki, AE and Farooqi, IS and Faul, JD and Fauser, S and Feng, S and Ferrannini, E and Ferrieres, J and Florez, JC and Ford, I and Fornage, M and Franco, OH and Franke, A and Franks, PW and Friedrich, N and Frikke-Schmidt, R and Galesloot, TE and Gan, W and Gandin, I and Gasparini, P and Gibson, J and Giedraitis, V and Gjesing, AP and Gordon-Larsen, P and Gorski, M and Grabe, HJ and Grant, SFA and Grarup, N and Griffiths, HL and Grove, ML and Gudnason, V and Gustafsson, S and Haessler, J and Hakonarson, H and Hammerschlag, AR and Hansen, T and Harris, KM and Harris, TB and Hattersley, AT and Have, CT and Hayward, C and He, L and Heard-Costa, NL and Heath, AC and Heid, IM and Helgeland, Ø and Hernesniemi, J and Hewitt, AW and Holmen, OL and Hovingh, GK and Howson, JMM and Hu, Y and Huang, PL and Huffman, JE and Ikram, MA and Ingelsson, E and Jackson, AU and Jansson, JH and Jarvik, GP and Jensen, GB and Jia, Y and Johansson, S and Jørgensen, ME and Jørgensen, T and Jukema, JW and Kahali, B and Kahn, RS and Kähönen, M and Kamstrup, PR and Kanoni, S and Kaprio, J and Karaleftheri, M and Kardia, SLR and Karpe, F and Kathiresan, S and Kee, F and Kiemeney, LA and Kim, E and Kitajima, H and Komulainen, P and Kooner, JS and Kooperberg, C and Korhonen, T and Kovacs, P and Kuivaniemi, H and Kutalik, Z and Kuulasmaa, K and Kuusisto, J and Laakso, M and Lakka, TA and Lamparter, D and Lange, EM and Lange, LA and Langenberg, C and Larson, EB and Lee, NR and Lehtimäki, T and Lewis, CE and Li, H and Li, J and Li-Gao, R and Lin, H and Lin, KH and Lin, LA and Lin, X and Lind, L and Lindström, J and Linneberg, A and Liu, CT and Liu, DJ and Liu, Y and Lo, KS and Lophatananon, A and Lotery, AJ and Loukola, A and Luan, J and Lubitz, SA and Lyytikäinen, LP and Männistö, S and Marenne, G and Mazul, AL and McCarthy, MI and McKean-Cowdin, R and Medland, SE and Meidtner, K and Milani, L and Mistry, V and Mitchell, P and Mohlke, KL and Moilanen, L and Moitry, M and Montgomery, GW and Mook-Kanamori, DO and Moore, C and Mori, TA and Morris, AD and Morris, AP and Müller-Nurasyid, M and Munroe, PB and Nalls, MA and Narisu, N and Nelson, CP and Neville, M and Nielsen, SF and Nikus, K and Njølstad, PR and Nordestgaard, BG and Nyholt, DR and O'Connel, JR and O'Donoghue, ML and Olde Loohuis, LM and Ophoff, RA and Owen, KR and Packard, CJ and Padmanabhan, S and Palmer, CNA and Palmer, ND and Pasterkamp, G and Patel, AP and Pattie, A and Pedersen, O and Peissig, PL and Peloso, GM and Pennell, CE and Perola, M and Perry, JA and Perry, JRB and Pers, TH and Person, TN and Peters, A and Petersen, ERB and Peyser, PA and Pirie, A and Polasek, O and Polderman, TJ and Puolijoki, H and Raitakari, OT and Rasheed, A and Rauramaa, R and Reilly, DF and Renström, F and Rheinberger, M and Ridker, PM and Rioux, JD and Rivas, MA and Roberts, DJ and Robertson, NR and Robino, A and Rolandsson, O and Rudan, I and Ruth, KS and Saleheen, D and Salomaa, V and Samani, NJ and Sapkota, Y and Sattar, N and Schoen, RE and Schreiner, PJ and Schulze, MB and Scott, RA and Segura-Lepe, MP and Shah, SH and Sheu, WH and Sim, X and Slater, AJ and Small, KS and Smith, AV and Southam, L and Spector, TD and Speliotes, EK and Starr, JM and Stefansson, K and Steinthorsdottir, V and Stirrups, KE and Strauch, K and Stringham, HM and Stumvoll, M and Sun, L and Surendran, P and Swift, AJ and Tada, H and Tansey, KE and Tardif, JC and Taylor, KD and Teumer, A and Thompson, DJ and Thorleifsson, G and Thorsteinsdottir, U and Thuesen, BH and Tönjes, A and Tromp, G and Trompet, S and Tsafantakis, E and Tuomilehto, J and Tybjaerg-Hansen, A and Tyrer, JP and Uher, R and Uitterlinden, AG and Uusitupa, M and Laan, SW and Duijn, CM and Leeuwen, N and van Setten, J and Vanhala, M and Varbo, A and Varga, TV and Varma, R and Velez Edwards, DR and Vermeulen, SH and Veronesi, G and Vestergaard, H and Vitart, V and Vogt, TF and Völker, U and Vuckovic, D and Wagenknecht, LE and Walker, M and Wallentin, L and Wang, F and Wang, CA and Wang, S and Wang, Y and Ware, EB and Wareham, NJ and Warren, HR and Waterworth, DM and Wessel, J and White, HD and Willer, CJ and Wilson, JG and Witte, DR and Wood, AR and Wu, Y and Yaghootkar, H and Yao, J and Yao, P and Yerges-Armstrong, LM and Young, R and Zeggini, E and Zhan, X and Zhang, W and Zhao, JH and Zhao, W and Zhao, W and Zhou, W and Zondervan, KT and Rotter, JI and Pospisilik, JA and Rivadeneira, F and Borecki, IB and Deloukas, P and Frayling, TM and Lettre, G and North, KE and Lindgren, CM and Hirschhorn, JN and Loos, RJF and , and , and , and , and , and , and , and , and , and , and , }, title = {Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure in obesity.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {26-41}, pmid = {29273807}, issn = {1546-1718}, support = {R01 DK093757/DK/NIDDK NIH HHS/United States ; U01 HG007417/HG/NHGRI NIH HHS/United States ; G9521010//Medical Research Council/United Kingdom ; K99 HL130580/HL/NHLBI NIH HHS/United States ; R01 DK106621/DK/NIDDK NIH HHS/United States ; RG/13/13/30194//British Heart Foundation/United Kingdom ; K24 HL105780/HL/NHLBI NIH HHS/United States ; R01 HL109946/HL/NHLBI NIH HHS/United States ; R01 HL057818/HL/NHLBI NIH HHS/United States ; R01 DK106236/DK/NIDDK NIH HHS/United States ; R01 HL092577/HL/NHLBI NIH HHS/United States ; U01 HG007416/HG/NHGRI NIH HHS/United States ; K01 DK107836/DK/NIDDK NIH HHS/United States ; T32 CA009156/CA/NCI NIH HHS/United States ; SP/13/2/30111//British Heart Foundation/United Kingdom ; R21 DA040177/DA/NIDA NIH HHS/United States ; RG/08/014/24067//British Heart Foundation/United Kingdom ; KL2 TR001109/TR/NCATS NIH HHS/United States ; R00 HL130580/HL/NHLBI NIH HHS/United States ; MR/L01632X/1//Medical Research Council/United Kingdom ; MC_UU_12015/7//Medical Research Council/United Kingdom ; R25 CA094880/CA/NCI NIH HHS/United States ; R01 DK110113/DK/NIDDK NIH HHS/United States ; R01 DK107786/DK/NIDDK NIH HHS/United States ; R01 DK075787/DK/NIDDK NIH HHS/United States ; F31 HG009850/HG/NHGRI NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; MR/L01341X/1//Medical Research Council/United Kingdom ; MR/K026992/1//Medical Research Council/United Kingdom ; MR/L003120/1//Medical Research Council/United Kingdom ; S10 OD018522/OD/NIH HHS/United States ; R01 HL128914/HL/NHLBI NIH HHS/United States ; G0601966//Medical Research Council/United Kingdom ; MC_UU_12015/1//Medical Research Council/United Kingdom ; K99 HL094535/HL/NHLBI NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 HG008983/HG/NHGRI NIH HHS/United States ; P30 DK063491/DK/NIDDK NIH HHS/United States ; MC_UU_12015/2//Medical Research Council/United Kingdom ; R01 DK101855/DK/NIDDK NIH HHS/United States ; R00 HL094535/HL/NHLBI NIH HHS/United States ; MC_PC_U127561128//Medical Research Council/United Kingdom ; MR/M501633/2//Medical Research Council/United Kingdom ; U01 DK062370/DK/NIDDK NIH HHS/United States ; T32 GM096911/GM/NIGMS NIH HHS/United States ; R01 DK107904/DK/NIDDK NIH HHS/United States ; R01 DK089256/DK/NIDDK NIH HHS/United States ; MR/K006584/1//Medical Research Council/United Kingdom ; P30 DK020572/DK/NIDDK NIH HHS/United States ; RG/14/5/30893//British Heart Foundation/United Kingdom ; MR/K007017/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; 323195//European Research Council/International ; R01 HD057194/HD/NICHD NIH HHS/United States ; BB/F019394/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; Z99 AG999999/NULL/Intramural NIH HHS/United States ; MC_PC_13040//Medical Research Council/United Kingdom ; UL1 TR001881/TR/NCATS NIH HHS/United States ; T32 HL007055/HL/NHLBI NIH HHS/United States ; G0600237//Medical Research Council/United Kingdom ; 293574//European Research Council/International ; R01 NS033335/NS/NINDS NIH HHS/United States ; L30 HL140353/HL/NHLBI NIH HHS/United States ; K23 HL114724/HL/NHLBI NIH HHS/United States ; Z01 AG000932-01/NULL/Intramural NIH HHS/United States ; R21 HL121422/HL/NHLBI NIH HHS/United States ; MR/M501633/1//Medical Research Council/United Kingdom ; }, abstract = {Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.}, } @article {pmid29273806, year = {2018}, author = {Demenais, F and Margaritte-Jeannin, P and Barnes, KC and Cookson, WOC and Altmüller, J and Ang, W and Barr, RG and Beaty, TH and Becker, AB and Beilby, J and Bisgaard, H and Bjornsdottir, US and Bleecker, E and Bønnelykke, K and Boomsma, DI and Bouzigon, E and Brightling, CE and Brossard, M and Brusselle, GG and Burchard, E and Burkart, KM and Bush, A and Chan-Yeung, M and Chung, KF and Couto Alves, A and Curtin, JA and Custovic, A and Daley, D and de Jongste, JC and Del-Rio-Navarro, BE and Donohue, KM and Duijts, L and Eng, C and Eriksson, JG and Farrall, M and Fedorova, Y and Feenstra, B and Ferreira, MA and , and Freidin, MB and Gajdos, Z and Gauderman, J and Gehring, U and Geller, F and Genuneit, J and Gharib, SA and Gilliland, F and Granell, R and Graves, PE and Gudbjartsson, DF and Haahtela, T and Heckbert, SR and Heederik, D and Heinrich, J and Heliövaara, M and Henderson, J and Himes, BE and Hirose, H and Hirschhorn, JN and Hofman, A and Holt, P and Hottenga, J and Hudson, TJ and Hui, J and Imboden, M and Ivanov, V and Jaddoe, VWV and James, A and Janson, C and Jarvelin, MR and Jarvis, D and Jones, G and Jonsdottir, I and Jousilahti, P and Kabesch, M and Kähönen, M and Kantor, DB and Karunas, AS and Khusnutdinova, E and Koppelman, GH and Kozyrskyj, AL and Kreiner, E and Kubo, M and Kumar, R and Kumar, A and Kuokkanen, M and Lahousse, L and Laitinen, T and Laprise, C and Lathrop, M and Lau, S and Lee, YA and Lehtimäki, T and Letort, S and Levin, AM and Li, G and Liang, L and Loehr, LR and London, SJ and Loth, DW and Manichaikul, A and Marenholz, I and Martinez, FJ and Matheson, MC and Mathias, RA and Matsumoto, K and Mbarek, H and McArdle, WL and Melbye, M and Melén, E and Meyers, D and Michel, S and Mohamdi, H and Musk, AW and Myers, RA and Nieuwenhuis, MAE and Noguchi, E and O'Connor, GT and Ogorodova, LM and Palmer, CD and Palotie, A and Park, JE and Pennell, CE and Pershagen, G and Polonikov, A and Postma, DS and Probst-Hensch, N and Puzyrev, VP and Raby, BA and Raitakari, OT and Ramasamy, A and Rich, SS and Robertson, CF and Romieu, I and Salam, MT and Salomaa, V and Schlünssen, V and Scott, R and Selivanova, PA and Sigsgaard, T and Simpson, A and Siroux, V and Smith, LJ and Solodilova, M and Standl, M and Stefansson, K and Strachan, DP and Stricker, BH and Takahashi, A and Thompson, PJ and Thorleifsson, G and Thorsteinsdottir, U and Tiesler, CMT and Torgerson, DG and Tsunoda, T and Uitterlinden, AG and van der Valk, RJP and Vaysse, A and Vedantam, S and von Berg, A and von Mutius, E and Vonk, JM and Waage, J and Wareham, NJ and Weiss, ST and White, WB and Wickman, M and Widén, E and Willemsen, G and Williams, LK and Wouters, IM and Yang, JJ and Zhao, JH and Moffatt, MF and Ober, C and Nicolae, DL}, title = {Multiancestry association study identifies new asthma risk loci that colocalize with immune-cell enhancer marks.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {42-53}, pmid = {29273806}, issn = {1546-1718}, support = {G0401540//Medical Research Council/United Kingdom ; P30 ES006694/ES/NIEHS NIH HHS/United States ; U01 HL130114/HL/NHLBI NIH HHS/United States ; R01 HL077612/HL/NHLBI NIH HHS/United States ; MR/K002449/1//Medical Research Council/United Kingdom ; G0601361//Medical Research Council/United Kingdom ; MC_UU_12015/1//Medical Research Council/United Kingdom ; RC2 HL101651/HL/NHLBI NIH HHS/United States ; 648916//European Research Council/International ; G0902125//Medical Research Council/United Kingdom ; G9815508//Medical Research Council/United Kingdom ; P30 ES009089/ES/NIEHS NIH HHS/United States ; }, abstract = {We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.}, } @article {pmid29273805, year = {2018}, author = {Melnyk, RA and Haney, CH}, title = {Bacterial genomics of plant adaptation.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {2-4}, doi = {10.1038/s41588-017-0019-2}, pmid = {29273805}, issn = {1546-1718}, } @article {pmid29273804, year = {2018}, author = {Rada-Iglesias, A}, title = {Is H3K4me1 at enhancers correlative or causative?.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {4-5}, doi = {10.1038/s41588-017-0018-3}, pmid = {29273804}, issn = {1546-1718}, } @article {pmid29273803, year = {2018}, author = {Hoffman, GE and Brennand, KJ}, title = {Mapping regulatory variants in hiPSC models.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {1-2}, doi = {10.1038/s41588-017-0017-4}, pmid = {29273803}, issn = {1546-1718}, } @article {pmid29273440, year = {2018}, author = {Wang, JS and Infante, CR and Park, S and Menke, DB}, title = {PITX1 promotes chondrogenesis and myogenesis in mouse hindlimbs through conserved regulatory targets.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {186-195}, pmid = {29273440}, issn = {1095-564X}, support = {R01 HD081034/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Chondrogenesis/*physiology ; Hindlimb/cytology/*embryology ; Homeodomain Proteins/genetics/metabolism ; Lizards/embryology ; Mice ; Mice, Inbred ICR ; Mice, Knockout ; Muscle Development/*physiology ; Paired Box Transcription Factors/genetics/*metabolism ; Reptilian Proteins/genetics/metabolism ; SOX9 Transcription Factor/genetics/metabolism ; Transcription, Genetic/*physiology ; }, abstract = {The PITX1 transcription factor is expressed during hindlimb development, where it plays a critical role in directing hindlimb growth and the specification of hindlimb morphology. While it is known that PITX1 regulates hindlimb formation, in part, through activation of the Tbx4 gene, other transcriptional targets remain to be elucidated. We have used a combination of ChIP-seq and RNA-seq to investigate enhancer regions and target genes that are directly regulated by PITX1 in embryonic mouse hindlimbs. In addition, we have analyzed PITX1 binding sites in hindlimbs of Anolis lizards to identify ancient PITX1 regulatory targets. We find that PITX1-bound regions in both mouse and Anolis hindlimbs are strongly associated with genes implicated in limb and skeletal system development. Gene expression analyses reveal a large number of misexpressed genes in the hindlimbs of Pitx1-/- mouse embryos. By intersecting misexpressed genes with genes that have neighboring mouse PITX1 binding sites, we identified 440 candidate targets of PITX1. Of these candidates, 68 exhibit ultra-conserved PITX1 binding events that are shared between mouse and Anolis hindlimbs. Among the ancient targets of PITX1 are important regulators of cartilage and skeletal muscle development, including Sox9 and Six1. Our data suggest that PITX1 promotes chondrogenesis and myogenesis in the hindlimb by direct regulation of several key members of the cartilage and muscle transcriptional networks.}, } @article {pmid29272536, year = {2018}, author = {Alexandre, CM and Urton, JR and Jean-Baptiste, K and Huddleston, J and Dorrity, MW and Cuperus, JT and Sullivan, AM and Bemm, F and Jolic, D and Arsovski, AA and Thompson, A and Nemhauser, JL and Fields, S and Weigel, D and Bubb, KL and Queitsch, C}, title = {Complex Relationships between Chromatin Accessibility, Sequence Divergence, and Gene Expression in Arabidopsis thaliana.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {837-854}, pmid = {29272536}, issn = {1537-1719}, support = {T32 CA206089/CA/NCI NIH HHS/United States ; }, abstract = {Variation in regulatory DNA is thought to drive phenotypic variation, evolution, and disease. Prior studies of regulatory DNA and transcription factors across animal species highlighted a fundamental conundrum: Transcription factor binding domains and cognate binding sites are conserved, while regulatory DNA sequences are not. It remains unclear how conserved transcription factors and dynamic regulatory sites produce conserved expression patterns across species. Here, we explore regulatory DNA variation and its functional consequences within Arabidopsis thaliana, using chromatin accessibility to delineate regulatory DNA genome-wide. Unlike in previous cross-species comparisons, the positional homology of regulatory DNA is maintained among A. thaliana ecotypes and less nucleotide divergence has occurred. Of the ∼50,000 regulatory sites in A. thaliana, we found that 15% varied in accessibility among ecotypes. Some of these accessibility differences were associated with extensive, previously unannotated sequence variation, encompassing many deletions and ancient hypervariable alleles. Unexpectedly, for the majority of such regulatory sites, nearby gene expression was unaffected. Nevertheless, regulatory sites with high levels of sequence variation and differential chromatin accessibility were the most likely to be associated with differential gene expression. Finally, and most surprising, we found that the vast majority of differentially accessible sites show no underlying sequence variation. We argue that these surprising results highlight the necessity to consider higher-order regulatory context in evaluating regulatory variation and predicting its phenotypic consequences.}, } @article {pmid29272453, year = {2018}, author = {Pérez-Brocal, V and Andremont, A and Moya, A}, title = {Isolation in small populations of Wayampi Amerindians promotes endemicity and homogenisation of their faecal virome, but its distribution is not entirely random.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix184}, pmid = {29272453}, issn = {1574-6941}, abstract = {The isolated community of the Wayampi Amerindians has been extensively studied for the presence of beta lactamase-producing enterobacteria and their gut microbiota. However, no information about their virome was available. This study tries to establish potential associations between the virome and diverse epidemiological data, through the metagenomic study of the faecal prophages and DNA viruses from 31 samples collected in 2010. Taxonomic assignments, composition, abundance and diversity analyses were obtained to characterise the virome and were compared between groups according to several demographic, environmental and medical data. Prophages outnumbered viruses. Composition and abundance of virome indicated relatively low variability. Diversity within samples showed no significant differences, regardless of the group comparison. Significant differences were observed in the beta diversity among samples according to hospitalisation and gender, but not by extended spectrum β-lactamase carriage, antibiotic intake or possession of pets, although some viruses differed in some cases (e.g. immunodeficiency-associated stool virus associated with antibiotic intake). The faecal virome of adult Wayampi is more homogeneous than that from western populations. Not a single factor analysed can explain alone the observed distribution of the virome, but differences by gender (fewer variability in females than males) may reflect differences in life habits and work.}, } @article {pmid29272410, year = {2018}, author = {Brito, PH and Chevreux, B and Serra, CR and Schyns, G and Henriques, AO and Pereira-Leal, JB}, title = {Genetic Competence Drives Genome Diversity in Bacillus subtilis.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {108-124}, pmid = {29272410}, issn = {1759-6653}, mesh = {Bacillus subtilis/*genetics ; Bacterial Proteins/genetics ; Evolution, Molecular ; Gene Transfer, Horizontal ; Genes, Bacterial ; *Genetic Variation ; Genome, Bacterial ; Phylogeny ; }, abstract = {Prokaryote genomes are the result of a dynamic flux of genes, with increases achieved via horizontal gene transfer and reductions occurring through gene loss. The ecological and selective forces that drive this genomic flexibility vary across species. Bacillus subtilis is a naturally competent bacterium that occupies various environments, including plant-associated, soil, and marine niches, and the gut of both invertebrates and vertebrates. Here, we quantify the genomic diversity of B. subtilis and infer the genome dynamics that explain the high genetic and phenotypic diversity observed. Phylogenomic and comparative genomic analyses of 42 B. subtilis genomes uncover a remarkable genome diversity that translates into a core genome of 1,659 genes and an asymptotic pangenome growth rate of 57 new genes per new genome added. This diversity is due to a large proportion of low-frequency genes that are acquired from closely related species. We find no gene-loss bias among wild isolates, which explains why the cloud genome, 43% of the species pangenome, represents only a small proportion of each genome. We show that B. subtilis can acquire xenologous copies of core genes that propagate laterally among strains within a niche. While not excluding the contributions of other mechanisms, our results strongly suggest a process of gene acquisition that is largely driven by competence, where the long-term maintenance of acquired genes depends on local and global fitness effects. This competence-driven genomic diversity provides B. subtilis with its generalist character, enabling it to occupy a wide range of ecological niches and cycle through them.}, } @article {pmid29272407, year = {2018}, author = {Sazinas, P and Redgwell, T and Rihtman, B and Grigonyte, A and Michniewski, S and Scanlan, DJ and Hobman, J and Millard, A}, title = {Comparative Genomics of Bacteriophage of the Genus Seuratvirus.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {72-76}, pmid = {29272407}, issn = {1759-6653}, support = {MR/L015080/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Bacteriophages/*genetics ; Cattle/*virology ; Genetic Variation ; Genome, Viral ; Genomics/*methods ; Phylogeny ; }, abstract = {Despite being more abundant and having smaller genomes than their bacterial host, relatively few bacteriophages have had their genomes sequenced. Here, we isolated 14 bacteriophages from cattle slurry and performed de novo genome sequencing, assembly, and annotation. The commonly used marker genes polB and terL showed these bacteriophages to be closely related to members of the genus Seuratvirus. We performed a core-gene analysis using the 14 new and four closely related genomes. A total of 58 core genes were identified, the majority of which has no known function. These genes were used to construct a core-gene phylogeny, the results of which confirmed the new isolates to be part of the genus Seuratvirus and expanded the number of species within this genus to four. All bacteriophages within the genus contained the genes queCDE encoding enzymes involved in queuosine biosynthesis. We suggest these genes are carried as a mechanism to modify DNA in order to protect these bacteriophages against host endonucleases.}, } @article {pmid29272394, year = {2018}, author = {Mollion, M and Ehlers, BK and Figuet, E and Santoni, S and Lenormand, T and Maurice, S and Galtier, N and Bataillon, T}, title = {Patterns of Genome-Wide Nucleotide Diversity in the Gynodioecious Plant Thymus vulgaris Are Compatible with Recent Sweeps of Cytoplasmic Genes.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {239-248}, pmid = {29272394}, issn = {1759-6653}, mesh = {Cell Nucleus/genetics ; Cytoplasm/genetics ; Evolution, Molecular ; *Genetic Variation ; Genome, Plant ; *Polymorphism, Single Nucleotide ; Selection, Genetic ; Thymus Plant/*genetics ; Transcriptome ; }, abstract = {Gynodioecy is a sexual dimorphism where females coexist with hermaphrodite individuals. In most cases, this dimorphism involves the interaction of cytoplasmic male sterility (CMS) genes and nuclear restorer genes. Two scenarios can account for how these interactions maintain gynodioecy. Either CMS genes recurrently enter populations at low frequency via mutation or migration and go to fixation unimpeded (successive sweeps), or CMS genes maintain polymorphism over evolutionary time through interactions with a nuclear restorer allele (balanced polymorphism). To distinguish between these scenarios, we used transcriptome sequencing in gynodioecious Thymus vulgaris and surveyed genome-wide diversity in 18 naturally occurring individuals sampled from populations at a local geographic scale. We contrast the amount and patterns of nucleotide diversity in the nuclear and cytoplasmic genome, and find ample diversity at the nuclear level (π = 0.019 at synonymous sites) but reduced genetic diversity and an excess of rare polymorphisms in the cytoplasmic genome relative to the nuclear genome. Our finding is incompatible with the maintenance of gynodioecy via scenarios invoking long-term balancing selection, and instead suggests the recent fixation of CMS lineages in the populations studied.}, } @article {pmid29272384, year = {2018}, author = {Viana, F and Paz, LC and Methling, K and Damgaard, CF and Lalk, M and Schramm, A and Lund, MB}, title = {Distinct effects of the nephridial symbionts Verminephrobacter and Candidatus Nephrothrix on reproduction and maturation of its earthworm host Eisenia andrei.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix178}, pmid = {29272384}, issn = {1574-6941}, abstract = {Verminephrobacter, the most common specific symbionts in the nephridia (excretory organs) of lumbricid earthworms, have been shown to improve reproduction of the garden earthworm Aporrectodea tuberculata under nutrient limitation. It is unknown how general this beneficial trait is in the Verminephrobacter-earthworm symbiosis, whether other nephridial symbionts also affect host fitness and what the mechanism of the fitness increase is. Here we report beneficial effects of Verminephrobacter and Candidatus Nephrothrix on life history traits of the compost worm Eisenia andrei, which in addition to these two symbionts also hosts Agromyces-like bacteria in its mixed nephridial community: while growth was identical between control, Verminephrobacter-free and aposymbiotic worms, control worms produced significantly more cocoons and offspring than both Verminephrobacter-free and aposymbiotic worms, confirming the reproductive benefit of Verminephrobacter in a second host with different ecology and feeding behavior. Furthermore, worms with Verminephrobacter and Ca. Nephrothrix, or with only Ca. Nephrothrix present, reached sexual maturity significantly earlier than aposymbiotic worms; this is the first evidence for a beneficial role of Ca. Nephrothrix in earthworms. Riboflavin content in cocoons and whole earthworms was unaffected by the presence or absence of nephridial symbionts, suggesting that nutritional supplementation with this vitamin does not play a major role in this symbiosis.}, } @article {pmid29272370, year = {2018}, author = {Laenen, L and Vergote, V and Kafetzopoulou, LE and Wawina, TB and Vassou, D and Cook, JA and Hugot, JP and Deboutte, W and Kang, HJ and Witkowski, PT and Köppen-Rung, P and Krüger, DH and Licková, M and Stang, A and Striešková, L and Szemeš, T and Markowski, J and Hejduk, J and Kafetzopoulos, D and Van Ranst, M and Yanagihara, R and Klempa, B and Maes, P}, title = {A Novel Hantavirus of the European Mole, Bruges Virus, Is Involved in Frequent Nova Virus Coinfections.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {45-55}, pmid = {29272370}, issn = {1759-6653}, support = {P20 GM103516/GM/NIGMS NIH HHS/United States ; R01 AI075057/AI/NIAID NIH HHS/United States ; U54 MD007601/MD/NIMHD NIH HHS/United States ; }, mesh = {Animals ; Coinfection ; Europe/epidemiology ; Evolution, Molecular ; Genome, Viral ; Hantavirus/*genetics/physiology ; Hantavirus Infections/epidemiology/*virology ; Host-Pathogen Interactions ; Humans ; Moles/*virology ; *Phylogeny ; }, abstract = {Hantaviruses are zoonotic viruses with a complex evolutionary history of virus-host coevolution and cross-species transmission. Although hantaviruses have a broad reservoir host range, virus-host relationships were previously thought to be strict, with a single virus species infecting a single host species. Here, we describe Bruges virus, a novel hantavirus harbored by the European mole (Talpa europaea), which is the well-known host of Nova virus. Phylogenetic analyses of all three genomic segments showed tree topology inconsistencies, suggesting that Bruges virus has emerged from cross-species transmission and ancient reassortment events. A high number of coinfections with Bruges and Nova viruses was detected, but no evidence was found for reassortment between these two hantaviruses. These findings highlight the complexity of hantavirus evolution and the importance of further investigation of hantavirus-reservoir relationships.}, } @article {pmid29272143, year = {2018}, author = {Baddeley, D and Bewersdorf, J}, title = {Biological Insight from Super-Resolution Microscopy: What We Can Learn from Localization-Based Images.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {965-989}, doi = {10.1146/annurev-biochem-060815-014801}, pmid = {29272143}, issn = {1545-4509}, support = {R01 GM118486/GM/NIGMS NIH HHS/United States ; }, abstract = {Super-resolution optical imaging based on the switching and localization of individual fluorescent molecules [photoactivated localization microscopy (PALM), stochastic optical reconstruction microscopy (STORM), etc.] has evolved remarkably over the last decade. Originally driven by pushing technological limits, it has become a tool of biological discovery. The initial demand for impressive pictures showing well-studied biological structures has been replaced by a need for quantitative, reliable data providing dependable evidence for specific unresolved biological hypotheses. In this review, we highlight applications that showcase this development, identify the features that led to their success, and discuss remaining challenges and difficulties. In this context, we consider the complex topic of defining resolution for this imaging modality and address some of the more common analytical methods used with this data.}, } @article {pmid29269423, year = {2018}, author = {Kim, J and Yang, D and Oh, SH and An, K}, title = {Coherent single-atom superradiance.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6376}, pages = {662-666}, doi = {10.1126/science.aar2179}, pmid = {29269423}, issn = {1095-9203}, abstract = {Superradiance is a quantum phenomenon emerging in macroscopic systems whereby correlated single atoms cooperatively emit photons. Demonstration of controlled collective atom-field interactions has resulted from the ability to directly imprint correlations with an atomic ensemble. Here we report cavity-mediated coherent single-atom superradiance: Single atoms with predefined correlation traverse a high-quality factor cavity one by one, emitting photons cooperatively with the N atoms that have already gone through the cavity (N represents the number of atoms). Enhanced collective photoemission of N-squared dependence was observed even when the intracavity atom number was less than unity. The correlation among single atoms was achieved by nanometer-precision position control and phase-aligned state manipulation of atoms by using a nanohole-array aperture. Our results demonstrate a platform for phase-controlled atom-field interactions.}, } @article {pmid29269422, year = {2018}, author = {Sinha, NK and Iwasa, J and Shen, PS and Bass, BL}, title = {Dicer uses distinct modules for recognizing dsRNA termini.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {329-334}, pmid = {29269422}, issn = {1095-9203}, support = {R01 GM121706/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphate/chemistry ; Animals ; Cryoelectron Microscopy ; Drosophila Proteins/*chemistry/ultrastructure ; Protein Binding ; Protein Structure, Tertiary ; RNA Cleavage ; RNA Helicases/*chemistry/ultrastructure ; RNA, Double-Stranded/*chemistry ; RNA, Small Interfering/chemistry/metabolism ; RNA, Viral/chemistry/metabolism ; Ribonuclease III/*chemistry/ultrastructure ; Substrate Specificity ; }, abstract = {Invertebrates rely on Dicer to cleave viral double-stranded RNA (dsRNA), and Drosophila Dicer-2 distinguishes dsRNA substrates by their termini. Blunt termini promote processive cleavage, while 3' overhanging termini are cleaved distributively. To understand this discrimination, we used cryo-electron microscopy to solve structures of Drosophila Dicer-2 alone and in complex with blunt dsRNA. Whereas the Platform-PAZ domains have been considered the only Dicer domains that bind dsRNA termini, unexpectedly, we found that the helicase domain is required for binding blunt, but not 3' overhanging, termini. We further showed that blunt dsRNA is locally unwound and threaded through the helicase domain in an adenosine triphosphate-dependent manner. Our studies reveal a previously unrecognized mechanism for optimizing antiviral defense and set the stage for the discovery of helicase-dependent functions in other Dicers.}, } @article {pmid29269421, year = {2018}, author = {Murthy, PA and Neidig, M and Klemt, R and Bayha, L and Boettcher, I and Enss, T and Holten, M and Zürn, G and Preiss, PM and Jochim, S}, title = {High-temperature pairing in a strongly interacting two-dimensional Fermi gas.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {452-455}, doi = {10.1126/science.aan5950}, pmid = {29269421}, issn = {1095-9203}, abstract = {The nature of the normal phase of strongly correlated fermionic systems is an outstanding question in quantum many-body physics. We used spatially resolved radio-frequency spectroscopy to measure pairing energy of fermions across a wide range of temperatures and interaction strengths in a two-dimensional gas of ultracold fermionic atoms. We observed many-body pairing at temperatures far above the critical temperature for superfluidity. In the strongly interacting regime, the pairing energy in the normal phase considerably exceeds the intrinsic two-body binding energy of the system and shows a clear dependence on local density. This implies that pairing in this regime is driven by many-body correlations, rather than two-body physics. Our findings show that pairing correlations in strongly interacting two-dimensional fermionic systems are remarkably robust against thermal fluctuations.}, } @article {pmid29269420, year = {2018}, author = {Chittori, S and Hong, J and Saunders, H and Feng, H and Ghirlando, R and Kelly, AE and Bai, Y and Subramaniam, S}, title = {Structural mechanisms of centromeric nucleosome recognition by the kinetochore protein CENP-N.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {339-343}, pmid = {29269420}, issn = {1095-9203}, support = {Z01 BC010808-01/NULL/Intramural NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Animals ; Centromere/*metabolism ; Centromere Protein A/*metabolism ; Chromosomal Proteins, Non-Histone/*chemistry/genetics/metabolism/ultrastructure ; Cryoelectron Microscopy ; DNA Mutational Analysis ; Humans ; Kinetochores/metabolism ; Nucleosomes/*metabolism ; Protein Structure, Secondary ; Xenopus ; }, abstract = {Accurate chromosome segregation requires the proper assembly of kinetochore proteins. A key step in this process is the recognition of the histone H3 variant CENP-A in the centromeric nucleosome by the kinetochore protein CENP-N. We report cryo-electron microscopy (cryo-EM), biophysical, biochemical, and cell biological studies of the interaction between the CENP-A nucleosome and CENP-N. We show that human CENP-N confers binding specificity through interactions with the L1 loop of CENP-A, stabilized by electrostatic interactions with the nucleosomal DNA. Mutational analyses demonstrate analogous interactions in Xenopus, which are further supported by residue-swapping experiments involving the L1 loop of CENP-A. Our results are consistent with the coevolution of CENP-N and CENP-A and establish the structural basis for recognition of the CENP-A nucleosome to enable kinetochore assembly and centromeric chromatin organization.}, } @article {pmid29269395, year = {2018}, author = {Turchin, P and Currie, TE and Whitehouse, H and François, P and Feeney, K and Mullins, D and Hoyer, D and Collins, C and Grohmann, S and Savage, P and Mendel-Gleason, G and Turner, E and Dupeyron, A and Cioni, E and Reddish, J and Levine, J and Jordan, G and Brandl, E and Williams, A and Cesaretti, R and Krueger, M and Ceccarelli, A and Figliulo-Rosswurm, J and Tuan, PJ and Peregrine, P and Marciniak, A and Preiser-Kapeller, J and Kradin, N and Korotayev, A and Palmisano, A and Baker, D and Bidmead, J and Bol, P and Christian, D and Cook, C and Covey, A and Feinman, G and Júlíusson, ÁD and Kristinsson, A and Miksic, J and Mostern, R and Petrie, C and Rudiak-Gould, P and Ter Haar, B and Wallace, V and Mair, V and Xie, L and Baines, J and Bridges, E and Manning, J and Lockhart, B and Bogaard, A and Spencer, C}, title = {Quantitative historical analysis uncovers a single dimension of complexity that structures global variation in human social organization.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E144-E151}, pmid = {29269395}, issn = {1091-6490}, mesh = {Algorithms ; Archaeology/methods ; *Biological Evolution ; *Cultural Diversity ; *Cultural Evolution ; Geography ; History, Ancient ; Humans ; Models, Theoretical ; Social Change/*history ; Time Factors ; }, abstract = {Do human societies from around the world exhibit similarities in the way that they are structured, and show commonalities in the ways that they have evolved? These are long-standing questions that have proven difficult to answer. To test between competing hypotheses, we constructed a massive repository of historical and archaeological information known as "Seshat: Global History Databank." We systematically coded data on 414 societies from 30 regions around the world spanning the last 10,000 years. We were able to capture information on 51 variables reflecting nine characteristics of human societies, such as social scale, economy, features of governance, and information systems. Our analyses revealed that these different characteristics show strong relationships with each other and that a single principal component captures around three-quarters of the observed variation. Furthermore, we found that different characteristics of social complexity are highly predictable across different world regions. These results suggest that key aspects of social organization are functionally related and do indeed coevolve in predictable ways. Our findings highlight the power of the sciences and humanities working together to rigorously test hypotheses about general rules that may have shaped human history.}, } @article {pmid29269394, year = {2018}, author = {Zhang, Y and Qiu, Y and Blanchard, AT and Chang, Y and Brockman, JM and Ma, VP and Lam, WA and Salaita, K}, title = {Platelet integrins exhibit anisotropic mechanosensing and harness piconewton forces to mediate platelet aggregation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {325-330}, pmid = {29269394}, issn = {1091-6490}, support = {R01 HL130918/HL/NHLBI NIH HHS/United States ; U54 HL112309/HL/NHLBI NIH HHS/United States ; R21 HL130818/HL/NHLBI NIH HHS/United States ; R01 HL121264/HL/NHLBI NIH HHS/United States ; U01 HL117721/HL/NHLBI NIH HHS/United States ; R01 GM124472/GM/NIGMS NIH HHS/United States ; F99 CA223074/CA/NCI NIH HHS/United States ; }, mesh = {Anisotropy ; Biosensing Techniques ; Blood Platelets/chemistry/*metabolism ; Fibrinogen/metabolism ; Fluorescence Recovery After Photobleaching ; Humans ; Integrins/chemistry/*metabolism ; Ligands ; Lipid Bilayers/metabolism ; *Mechanotransduction, Cellular ; Platelet Activation ; *Platelet Aggregation ; Protein Binding ; Time-Lapse Imaging/methods ; }, abstract = {Platelet aggregation at the site of vascular injury is essential in clotting. During this process, platelets are bridged by soluble fibrinogen that binds surface integrin receptors. One mystery in the mechanism of platelet aggregation pertains to how resting platelets ignore soluble fibrinogen, the third most abundant protein in the bloodstream, and yet avidly bind immobile fibrinogen on the surface of other platelets at the primary injury site. We speculate that platelet integrins are mechanosensors that test their ligands across the platelet-platelet synapse. To investigate this model, we interrogate human platelets using approaches that include the supported lipid bilayer platform as well as DNA tension sensor technologies. Experiments suggest that platelet integrins require lateral forces to mediate platelet-platelet interactions. Mechanically labile ligands dampen platelet activation, and the onset of piconewton integrin tension coincides with calcium flux. Activated platelets display immobilized fibrinogen on their surface, thus mediating further recruitment of resting platelets. The distribution of integrin tension was shown to be spatially regulated through two myosin-signaling pathways, myosin light chain kinase and Rho-associated kinase. Finally, we discovered that the termination of integrin tension is coupled with the exposure of phosphatidylserine. Our work reveals the highest spatial and temporal resolution maps of platelet integrin mechanics and its role in platelet aggregation, suggesting that platelets are physical substrates for one another that establish mechanical feedback loops of activation. The results are reminiscent of mechanical regulation of the T-cell receptor, E-cadherin, and Notch pathways, suggesting a common feature for signaling at cell junctions.}, } @article {pmid29269393, year = {2018}, author = {Little, MS and Pellock, SJ and Walton, WG and Tripathy, A and Redinbo, MR}, title = {Structural basis for the regulation of β-glucuronidase expression by human gut Enterobacteriaceae.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E152-E161}, pmid = {29269393}, issn = {1091-6490}, support = {P30 CA016086/CA/NCI NIH HHS/United States ; P30 ES010126/ES/NIEHS NIH HHS/United States ; T32 GM008570/GM/NIGMS NIH HHS/United States ; }, mesh = {Amino Acid Sequence ; Bacterial Proteins/chemistry/*genetics/metabolism ; Binding Sites ; Crystallography, X-Ray ; DNA/chemistry/genetics/metabolism ; Enterobacteriaceae/enzymology/*genetics ; Escherichia coli/genetics/metabolism ; Gastrointestinal Microbiome/*genetics ; *Gene Expression Regulation, Bacterial ; Genes, Regulator/genetics ; Glucuronic Acid/chemistry/metabolism ; Glucuronidase/chemistry/*genetics/metabolism ; Humans ; Mutation ; Operon/genetics ; Sequence Homology, Amino Acid ; }, abstract = {The gut microbiota harbor diverse β-glucuronidase (GUS) enzymes that liberate glucuronic acid (GlcA) sugars from small-molecule conjugates and complex carbohydrates. However, only the Enterobacteriaceae family of human gut-associated Proteobacteria maintain a GUS operon under the transcriptional control of a glucuronide repressor, GusR. Despite its potential importance in Escherichia, Salmonella, Klebsiella, Shigella, and Yersinia opportunistic pathogens, the structure of GusR has not been examined. Here, we explore the molecular basis for GusR-mediated regulation of GUS expression in response to small-molecule glucuronides. Presented are 2.1-Å-resolution crystal structures of GusRs from Escherichia coli and Salmonella enterica in complexes with a glucuronide ligand. The GusR-specific DNA operator site in the regulatory region of the E. coli GUS operon is identified, and structure-guided GusR mutants pinpoint the residues essential for DNA binding and glucuronide recognition. Interestingly, the endobiotic estradiol-17-glucuronide and the xenobiotic indomethacin-acyl-glucuronide are found to exhibit markedly differential binding to these GusR orthologs. Using structure-guided mutations, we are able to transfer E. coli GusR's preferential DNA and glucuronide binding affinity to S. enterica GusR. Structures of putative GusR orthologs from GUS-encoding Firmicutes species also reveal functionally unique features of the Enterobacteriaceae GusRs. Finally, dominant-negative GusR variants are validated in cell-based studies. These data provide a molecular framework toward understanding the control of glucuronide utilization by opportunistic pathogens in the human gut.}, } @article {pmid29269392, year = {2018}, author = {Potting, C and Crochemore, C and Moretti, F and Nigsch, F and Schmidt, I and Manneville, C and Carbone, W and Knehr, J and DeJesus, R and Lindeman, A and Maher, R and Russ, C and McAllister, G and Reece-Hoyes, JS and Hoffman, GR and Roma, G and Müller, M and Sailer, AW and Helliwell, SB}, title = {Genome-wide CRISPR screen for PARKIN regulators reveals transcriptional repression as a determinant of mitophagy.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E180-E189}, pmid = {29269392}, issn = {1091-6490}, mesh = {*CRISPR-Cas Systems ; Cell Line, Tumor ; Cells, Cultured ; *Gene Expression Regulation ; Genome, Human/*genetics ; HCT116 Cells ; HEK293 Cells ; Humans ; Induced Pluripotent Stem Cells/metabolism ; Infant, Newborn ; Mitochondrial Degradation/*genetics ; Neurons/metabolism ; Phosphorylation ; Protein Kinases/genetics/metabolism ; Repressor Proteins/*genetics/metabolism ; Ubiquitin/metabolism ; Ubiquitin-Protein Ligases/*genetics/metabolism ; }, abstract = {PARKIN, an E3 ligase mutated in familial Parkinson's disease, promotes mitophagy by ubiquitinating mitochondrial proteins for efficient engagement of the autophagy machinery. Specifically, PARKIN-synthesized ubiquitin chains represent targets for the PINK1 kinase generating phosphoS65-ubiquitin (pUb), which constitutes the mitophagy signal. Physiological regulation of PARKIN abundance, however, and the impact on pUb accumulation are poorly understood. Using cells designed to discover physiological regulators of PARKIN abundance, we performed a pooled genome-wide CRISPR/Cas9 knockout screen. Testing identified genes individually resulted in a list of 53 positive and negative regulators. A transcriptional repressor network including THAP11 was identified and negatively regulates endogenous PARKIN abundance. RNAseq analysis revealed the PARKIN-encoding locus as a prime THAP11 target, and THAP11 CRISPR knockout in multiple cell types enhanced pUb accumulation. Thus, our work demonstrates the critical role of PARKIN abundance, identifies regulating genes, and reveals a link between transcriptional repression and mitophagy, which is also apparent in human induced pluripotent stem cell-derived neurons, a disease-relevant cell type.}, } @article {pmid29269391, year = {2018}, author = {Kwon, HK and Chen, HM and Mathis, D and Benoist, C}, title = {FoxP3 scanning mutagenesis reveals functional variegation and mild mutations with atypical autoimmune phenotypes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E253-E262}, pmid = {29269391}, issn = {1091-6490}, support = {R01 AI116834/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Autoimmune Diseases/*genetics/*pathology ; Binding Sites ; Chromosome Mapping ; DNA ; Forkhead Transcription Factors/genetics/*metabolism ; Gene Expression Regulation/*physiology ; Mice ; Models, Molecular ; Mutagenesis ; Mutation ; Nucleic Acid Conformation ; Protein Binding ; Protein Conformation ; }, abstract = {FoxP3+ regulatory T cells (Tregs) are a central element of immunological tolerance. FoxP3 is the key determining transcription factor of the Treg lineage, interacting with numerous cofactors and transcriptional targets to determine the many facets of Treg function. Its absence leads to devastating lymphoproliferation and autoimmunity in scurfy mutant mice and immunodysregulation polyendocrinopathy enteropathy X-linked (IPEX) patients. To finely map transcriptionally active regions of the protein, with respect to disease-causing variation, we performed a systematic alanine-scan mutagenesis of FoxP3, assessing mutational impacts on DNA binding and transcriptional activation or repression. The mutations affected transcriptional activation and repression in a variegated manner involving multiple regions of the protein and varying between different transcriptional targets of FoxP3. There appeared to be different modalities for target genes related to classic immunosuppressive function vs. those related to atypical or tissue-Treg functions. Relevance to in vivo Treg biology was established by introducing some of the subtle Foxp3 mutations into the mouse germline by CRISPR-based genome editing. The resulting mice showed Treg populations in normal numbers and exhibited no overt autoimmune manifestations. However, Treg functional defects were revealed upon competition or by system stress, manifest as a strikingly heightened susceptibility to provoked colitis, and conversely by greater resistance to tumors. These observations suggest that some of the missense mutations that segregate in human populations, but do not induce IPEX manifestations, may have unappreciated consequences in other diseases.}, } @article {pmid29269261, year = {2018}, author = {Mallo, M}, title = {Reassessing the Role of Hox Genes during Vertebrate Development and Evolution.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {209-217}, doi = {10.1016/j.tig.2017.11.007}, pmid = {29269261}, issn = {0168-9525}, mesh = {Animals ; Body Patterning/*genetics ; Evolution, Molecular ; Gene Expression Regulation, Developmental ; Genes, Homeobox/*genetics ; Limb Buds/embryology/*metabolism ; Models, Genetic ; *Multigene Family ; Vertebrates/embryology/*genetics ; }, abstract = {Since their discovery Hox genes have been at the core of the established models explaining the development and evolution of the vertebrate body plan as well as its paired appendages. Recent work brought new light to their role in the patterning processes along the main body axis. These studies show that Hox genes do not control the basic layout of the vertebrate body plan but carry out region-specific patterning instructions loaded on the derivatives of axial progenitors by Hox-independent processes. Furthermore, the finding that Hox clusters are embedded in functional chromatin domains, which critically impacts their expression, has significantly altered our understanding of the mechanisms of Hox gene regulation. This new conceptual framework has broadened our understanding of both limb development and the evolution of vertebrate paired appendages.}, } @article {pmid29269218, year = {2018}, author = {Feitosa, WB and Hwang, K and Morris, PL}, title = {Temporal and SUMO-specific SUMOylation contribute to the dynamics of Polo-like kinase 1 (PLK1) and spindle integrity during mouse oocyte meiosis.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {278-291}, pmid = {29269218}, issn = {1095-564X}, support = {R01 HD039024/HD/NICHD NIH HHS/United States ; R03 HD061471/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Cycle Proteins/*metabolism ; Female ; Kinetochores/metabolism ; Meiosis/*physiology ; Mice ; Oocytes/cytology/*metabolism ; Phosphorylation/physiology ; Protein-Serine-Threonine Kinases/*metabolism ; Proto-Oncogene Proteins/*metabolism ; SUMO-1 Protein/*metabolism ; Spindle Apparatus/*metabolism ; Sumoylation/*physiology ; }, abstract = {During mammalian meiosis, Polo-like kinase 1 (PLK1) is essential during cell cycle progression. In oocyte maturation, PLK1 expression is well characterized but timing of posttranslational modifications regulating its activity and subcellular localization are less clear. Small ubiquitin-related modifier (SUMO) posttranslational modifier proteins have been detected in mammalian gametes but their precise function during gametogenesis is largely unknown. In the present paper we report for mouse oocytes that both PLK1 and phosphorylated PLK1 undergo SUMOylation in meiosis II (MII) oocytes using immunocytochemistry, immunoprecipitation and in vitro SUMOylation assays. At MII, PLK1 is phosphorylated at threonine-210 and serine-137. MII oocyte PLK1 and phosphorylated PLK1 undergo SUMOylation by SUMO-1, -2 and -3 as shown by individual in vitro assays. Using these assays, forms of phosphorylated PLK1 normalized to PLK1 increased significantly and correlated with SUMOylated PLK1 levels. During meiotic progression and maturation, SUMO-1-SUMOylation of PLK1 is involved in spindle formation whereas SUMO-2/3-SUMOylation may regulate PLK1 activity at kinetochore-spindle attachment sites. Microtubule integrity is required for PLK1 localization with SUMO-1 but not with SUMO-2/3. Inhibition of SUMOylation disrupts proper meiotic bipolar spindle organization and spindle-kinetochore attachment. The data show that both temporal and SUMO-specific-SUMOylation play important roles in orchestrating functional dynamics of PLK1 during mouse oocyte meiosis, including subcellular compartmentalization.}, } @article {pmid29269028, year = {2018}, author = {Paul, AS and Duraisingh, MT}, title = {Targeting Plasmodium Proteases to Block Malaria Parasite Escape and Entry.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {95-97}, doi = {10.1016/j.pt.2017.11.012}, pmid = {29269028}, issn = {1471-5007}, support = {R21 AI128480/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Erythrocytes ; Humans ; Malaria ; *Parasites ; Peptide Hydrolases ; Plasmodium ; *Plasmodium falciparum ; Protozoan Proteins ; }, abstract = {Proliferation of malaria parasites in a host requires mechanisms to spread between red blood cells (RBCs). We discuss here the implications for biology and antimalarial drug development of companion studies that establish the requirement of two Plasmodium spp. proteases of the plasmepsin family in parasite egress from, and invasion into, RBCs.}, } @article {pmid29269027, year = {2018}, author = {McVeigh, P and McCusker, P and Robb, E and Wells, D and Gardiner, E and Mousley, A and Marks, NJ and Maule, AG}, title = {Reasons to Be Nervous about Flukicide Discovery.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {184-196}, doi = {10.1016/j.pt.2017.11.010}, pmid = {29269027}, issn = {1471-5007}, support = {BB/H009477/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Anthelmintics/*therapeutic use ; Drug Discovery/*trends ; Fasciola hepatica/physiology ; Fascioliasis/*drug therapy ; Receptors, G-Protein-Coupled/metabolism ; Research/*trends ; }, abstract = {The majority of anthelmintics dysregulate neuromuscular function, a fact most prominent for drugs against nematode parasites. In contrast to the strong knowledge base for nematode neurobiology, resource and tool deficits have prevented similar advances in flatworm parasites since those driven by bioimaging, immunocytochemistry, and neuropeptide biochemistry 20-30 years ago. However, recent developments are encouraging a renaissance in liver fluke neurobiology that can now support flukicide discovery. Emerging data promote neuromuscular signalling components, and especially G protein-coupled receptors (GPCRs), as next-generation targets. Here, we summarise these data and expose some of the new opportunities to accelerate progress towards GPCR-targeted flukicides for Fasciola hepatica.}, } @article {pmid29268982, year = {2018}, author = {Fehr, AR and Jankevicius, G and Ahel, I and Perlman, S}, title = {Viral Macrodomains: Unique Mediators of Viral Replication and Pathogenesis.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {598-610}, pmid = {29268982}, issn = {1878-4380}, support = {R01 NS036592/NS/NINDS NIH HHS/United States ; P30 CA086862/CA/NCI NIH HHS/United States ; R01 AI129269/AI/NIAID NIH HHS/United States ; P01 AI060699/AI/NIAID NIH HHS/United States ; //Wellcome Trust/United Kingdom ; }, abstract = {Viruses from the Coronaviridae, Togaviridae, and Hepeviridae families ​all contain genes that encode a conserved protein domain, called a macrodomain; however, the role of this domain during infection has remained enigmatic. The recent discovery that mammalian macrodomain proteins enzymatically remove ADP-ribose, a common post-translation modification, from proteins has led to an outburst of studies describing both the enzymatic activity and function of viral macrodomains. These new studies have defined these domains as de-ADP-ribosylating enzymes, which indicates that these viruses have evolved to counteract antiviral ADP-ribosylation, likely mediated by poly-ADP-ribose polymerases (PARPs). Here, we comprehensively review this rapidly expanding field, describing the structures and enzymatic activities of viral macrodomains, and discussing their roles in viral replication and pathogenesis.}, } @article {pmid29268981, year = {2018}, author = {Kelman, LM and Kelman, Z}, title = {Do Archaea Need an Origin of Replication?.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {172-174}, doi = {10.1016/j.tim.2017.12.001}, pmid = {29268981}, issn = {1878-4380}, mesh = {Archaea/*genetics/growth & development/metabolism ; Archaeal Proteins/genetics/metabolism ; Chromosomes, Archaeal/genetics ; DNA Replication/genetics/physiology ; DNA, Archaeal/genetics ; Genes, Archaeal/*genetics ; Microbial Viability/genetics ; Replication Origin/*genetics/*physiology ; }, abstract = {Chromosomal DNA replication starts at a specific region called an origin of replication. Until recently, all organisms were thought to require origins to replicate their chromosomes. It was recently discovered that some archaeal species do not utilize origins of replication under laboratory growth conditions.}, } @article {pmid29268980, year = {2018}, author = {Mostafa, A and Pleschka, S}, title = {Influenza H3N2 Vaccines: Recent Challenges.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {87-89}, doi = {10.1016/j.tim.2017.12.003}, pmid = {29268980}, issn = {1878-4380}, mesh = {Antigens, Viral/immunology ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Influenza A Virus, H3N2 Subtype/*immunology ; Influenza Vaccines/*immunology ; Influenza, Human/epidemiology ; }, abstract = {H3N2-subtype influenza A viruses are major causes of seasonal influenza epidemics. Emerging H3N2 variants require the annual adjustment of the vaccine strain. Recently, studies addressing the reduced effectiveness of current H3N2 vaccines have identified production-related substitutions in the viral hemagglutinin antigen as a possible cause for reduced vaccine efficacy.}, } @article {pmid29267960, year = {2018}, author = {Song, Y and Malmuthuge, N and Steele, MA and Guan, LL}, title = {Shift of hindgut microbiota and microbial short chain fatty acids profiles in dairy calves from birth to pre-weaning.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {3}, pages = {}, doi = {10.1093/femsec/fix179}, pmid = {29267960}, issn = {1574-6941}, abstract = {This study aimed to characterize mucosa- and digesta-associated microbiota in the hindgut (cecum, colon and rectum) of newborn (NB, n = 6), day 7 (n = 6), day 21 (n = 6) and day 42 (n = 6) Holstein bull calves using amplicon sequencing. The hindgut microbiota was diverse at birth, and mucosa-attached microbial community had higher individual variation than that of digesta-associated community. In total, 16 phyla were identified with Firmicutes, Bacteroidetes and Proteobacteria being the dominant microbial taxa in the hindgut. Quantitative real-time PCR analysis showed a significant age effect on the proportion of mucosa-attached Escherichia coli, Bifidobacterium, Clostridium cluster XIVa and Faecalibacterium prausnitzii. Especially, high abundance of mucosa-associated Escherichia was detected during the first week of life, suggesting higher chance of the pathogenic infection during this stage. The relative abundances of predicted microbial genes involved in amino acid metabolism, carbohydrate metabolism and energy metabolism were enriched, indicating the importance of hindgut microbiota in fermentation during the pre-weaned period. Moreover, the significant correlation between short-chain fatty acid concentration and mucosa-attached carbohydrate utilizing (Coprococcus 1, Blautia, Lachnospiraceae NC2004 group, etc.) and health-related bacteria (Escherichia-Shigella and Salmonella) suggests the importance of hindgut microbiota in the fermentation and health of dairy calves during pre-weaned period.}, } @article {pmid29267956, year = {2018}, author = {Abed, RMM and Kohls, K and Leloup, J and de Beer, D}, title = {Abundance and diversity of aerobic heterotrophic microorganisms and their interaction with cyanobacteria in the oxic layer of an intertidal hypersaline cyanobacterial mat.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix183}, pmid = {29267956}, issn = {1574-6941}, abstract = {Aerobic heterotrophic microorganisms (AH) play a significant role in carbon cycling in cyanobacterial mats; however, little is known about their abundance, diversity and interaction with cyanobacteria. Using catalyzed reporter deposition fluorescence in situ hybridization (CARD-FISH), bacterial counts in the mat's oxic layer reached a mean of 2.23 ± 0.4 × 1010 cells g-1. Cultivation of AH yielded strains belonging to Actinobacteria, Bacteroidetes, Firmicutes, Gammaproteobacteria and Haloarchaea. 16S rRNA bacterial sequences retrieved from the mat's oxic layer were related to Bacteroidetes, Chloroflexi and Proteobacteria, whereas archaeal sequences belonged to Crenarchaeota and Haloarchaea. Monocultures of cyanobacteria from the same mat were associated with different AH, although Bacteroidetes were found in most cultures. CARD-FISH showed that Bacteroidetes- and Chloroflexi-related bacteria were closely associated with filaments of Microcoleus chthonoplastes. The growth of an axenic culture of M. chthonoplastes PCC7420 was stimulated on the addition of a filtrate obtained from a non-axenic Microcoleus culture and containing only AH and released substances. In contrast, a similar filtrate from a non-axenic Cyanothece-related culture killed Cyanothece PCC 7418. We conclude that a diverse community of AH exist in close association with cyanobacteria in microbial mats and the interactions between AH and cyanobacteria are species-specific and involve the release of substances.}, } @article {pmid29267942, year = {2018}, author = {Doyle, SR and Laing, R and Bartley, DJ and Britton, C and Chaudhry, U and Gilleard, JS and Holroyd, N and Mable, BK and Maitland, K and Morrison, AA and Tait, A and Tracey, A and Berriman, M and Devaney, E and Cotton, JA and Sargison, ND}, title = {A Genome Resequencing-Based Genetic Map Reveals the Recombination Landscape of an Outbred Parasitic Nematode in the Presence of Polyploidy and Polyandry.}, journal = {Genome biology and evolution}, volume = {10}, number = {2}, pages = {396-409}, pmid = {29267942}, issn = {1759-6653}, support = {//Wellcome Trust/United Kingdom ; BB/M003949//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Chromosome Mapping ; Crosses, Genetic ; Female ; Genetic Linkage ; Genetic Variation ; Haemonchiasis/*parasitology/*veterinary ; Haemonchus/*genetics ; Male ; Polyploidy ; *Recombination, Genetic ; }, abstract = {The parasitic nematode Haemonchus contortus is an economically and clinically important pathogen of small ruminants, and a model system for understanding the mechanisms and evolution of traits such as anthelmintic resistance. Anthelmintic resistance is widespread and is a major threat to the sustainability of livestock agriculture globally; however, little is known about the genome architecture and parameters such as recombination that will ultimately influence the rate at which resistance may evolve and spread. Here, we performed a genetic cross between two divergent strains of H. contortus, and subsequently used whole-genome resequencing of a female worm and her brood to identify the distribution of genome-wide variation that characterizes these strains. Using a novel bioinformatic approach to identify variants that segregate as expected in a pseudotestcross, we characterized linkage groups and estimated genetic distances between markers to generate a chromosome-scale F1 genetic map. We exploited this map to reveal the recombination landscape, the first for any helminth species, demonstrating extensive variation in recombination rate within and between chromosomes. Analyses of these data also revealed the extent of polyandry, whereby at least eight males were found to have contributed to the genetic variation of the progeny analyzed. Triploid offspring were also identified, which we hypothesize are the result of nondisjunction during female meiosis or polyspermy. These results expand our knowledge of the genetics of parasitic helminths and the unusual life-history of H. contortus, and enhance ongoing efforts to understand the genetic basis of resistance to the drugs used to control these worms and for related species that infect livestock and humans throughout the world. This study also demonstrates the feasibility of using whole-genome resequencing data to directly construct a genetic map in a single generation cross from a noninbred nonmodel organism with a complex lifecycle.}, } @article {pmid29267902, year = {2018}, author = {Bellini, MI and Kumaresan, D and Tarlera, S and Murrell, JC and Fernández-Scavino, A}, title = {Identification of active denitrifiers by DNA-stable isotope probing and amplicon sequencing reveals Betaproteobacteria as responsible for attenuation of nitrate contamination in a low impacted aquifer.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix181}, pmid = {29267902}, issn = {1574-6941}, abstract = {Groundwater reservoirs constitute important freshwater resources. However, these ecosystems are highly vulnerable to contamination and have to rely on the resident microbiota to attenuate the impact of this contamination. Nitrate is one of the main contaminants found in groundwater, and denitrification is the main process that removes the compound. In this study, the response to nutrient load on indigenous microbial communities in groundwater from a low impacted aquifer in Uruguay was evaluated. Denitrification rates were measured in groundwater samples from three different sites with nitrate, acetate and pyrite amendments. Results showed that denitrification is feasible under in situ nitrate and electron donor concentrations, although the lack of readily available organic energy source would limit the attenuation of higher nitrate concentrations. DNA-stable isotope probing, combined with amplicon sequencing of 16S rRNA, nirS and nirK genes, was used to identify the active denitrifiers. Members of the phylum Betaproteobacteria were the dominant denitrifiers in two of three sites, with different families being observed; members of the genus Vogesella (Neisseriaceae) were key denitrifiers at one site, while the genera Dechloromonas (Rhodocyclaceae) and Comamonas (Comamonadaceae) were the main denitrifiers detected at the other sites.}, } @article {pmid29267881, year = {2018}, author = {Britstein, M and Saurav, K and Teta, R and Sala, GD and Bar-Shalom, R and Stoppelli, N and Zoccarato, L and Costantino, V and Steindler, L}, title = {Identification and chemical characterization of N-acyl-homoserine lactone quorum sensing signals across sponge species and time.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix182}, pmid = {29267881}, issn = {1574-6941}, abstract = {Marine sponges form symbiotic relationships with complex microbial communities, yet little is known about the mechanisms by which these microbes regulate their behavior through gene expression. Many bacterial communities regulate gene expression using chemical signaling termed quorum sensing. While a few previous studies have shown presence of N-acyl-homoserine lactone (AHL)-based quorum sensing in marine sponges, the chemical identity of AHL signals has been published for only two sponge species. In this study, we screened for AHLs in extracts from 15 sponge species (109 specimens in total) from the Mediterranean and Red Sea, using a wide-range AHL biosensor. This is the first time that AHL presence was examined over time in sponges. We detected the presence of AHL in 46% of the sponge species and found that AHL signals differ for certain sponge species in time and across sponge individuals. Furthermore, for the Mediterranean sponge species Sarcotragus fasciculatus, we identified 14 different AHLs. The constant presence of specific AHL molecules in all specimens, together with varying signaling molecules between the different specimens, makes Sa. fasciculatus a good model to further investigate the function of quorum sensing in sponge-associated bacteria. This study extends the knowledge of AHL-based quorum sensing in marine sponges.}, } @article {pmid29267872, year = {2018}, author = {Sherpa, S and Rioux, D and Goindin, D and Fouque, F and François, O and Després, L}, title = {At the Origin of a Worldwide Invasion: Unraveling the Genetic Makeup of the Caribbean Bridgehead Populations of the Dengue Vector Aedes aegypti.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {56-71}, pmid = {29267872}, issn = {1759-6653}, support = {001//World Health Organization/International ; }, mesh = {Aedes/*genetics ; Animals ; Caribbean Region/epidemiology ; Dengue/epidemiology/*transmission ; Genetic Variation ; Humans ; Insecticide Resistance ; Mosquito Vectors/*genetics ; Polymorphism, Single Nucleotide ; }, abstract = {Human-driven global environmental changes have considerably increased the risk of biological invasions, especially the spread of human parasites and their vectors. Among exotic species that have major impacts on public health, the dengue fever mosquito Aedes aegypti originating from Africa has spread worldwide during the last three centuries. Although considerable progress has been recently made in understanding the history of this invasion, the respective roles of human and abiotic factors in shaping patterns of genetic diversity remain largely unexplored. Using a genome-wide sample of genetic variants (3,530 ddRAD SNPs), we analyzed the genetic structure of Ae. aegypti populations in the Caribbean, the first introduced territories in the Americas. Fourteen populations were sampled in Guyane and in four islands of the Antilles that differ in climatic conditions, intensity of urbanization, and vector control history. The genetic diversity in the Caribbean was low (He = 0.14-0.17), as compared with a single African collection from Benin (He = 0.26) and site-frequency spectrum analysis detected an ancient bottleneck dating back ∼300 years ago, supporting a founder event during the introduction of Ae. aegypti. Evidence for a more recent bottleneck may be related to the eradication program undertaken on the American continent in the 1950s. Among 12 loci detected as FST-outliers, two were located in candidate genes for insecticide resistance (cytochrome P450 and voltage-gated sodium channel). Genome-environment association tests identified additional loci associated with human density and/or deltamethrin resistance. Our results highlight the high impact of human pressures on the demographic history and genetic variation of Ae. aegypti Caribbean populations.}, } @article {pmid29266729, year = {2018}, author = {Chen, S and Wang, F and Zhang, Y and Qin, S and Wei, S and Wang, S and Hu, C and Liu, B}, title = {Organic carbon availability limiting microbial denitrification in the deep vadose zone.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {980-992}, doi = {10.1111/1462-2920.14027}, pmid = {29266729}, issn = {1462-2920}, abstract = {Microbes in the deep vadose zone play an essential role in the mitigation of nitrate leaching; however, limited information is available on the mechanisms of microbial denitrification due to sampling difficulties. We experimentally studied the factors that affect denitrification in soils collected down to 10.5 meters deep along the soil profile. After an anoxic pre-incubation, denitrification rates moderately increased and the N2 O/(N2 O + N2) ratios declined while the microbial abundance and diversity did not change significantly in most of the layers. Denitrification rate was significantly enhanced and the abundance of the denitrification genes was simultaneously elevated by the increased availability of organic carbon in all studied layers, to a greater extent in the subsurface layers than in the surface layers, suggesting the severe scarcity of carbon in the deep vadose zone. The genera Pseudomonas and Bacillus, which are made up of a number of species that have been previously identified as denitrifiers in soil, were the major taxa that respond to carbon addition. Overall, our results suggested that the limited denitrification in the deep vadose zone is not because of the lack of denitrifiers, but due to the low abundance of denitrifiers which is caused by low carbon availability.}, } @article {pmid29266706, year = {2018}, author = {Flegontova, O and Flegontov, P and Malviya, S and Poulain, J and de Vargas, C and Bowler, C and Lukeš, J and Horák, A}, title = {Neobodonids are dominant kinetoplastids in the global ocean.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {878-889}, doi = {10.1111/1462-2920.14034}, pmid = {29266706}, issn = {1462-2920}, abstract = {Kinetoplastid flagellates comprise basal mostly free-living bodonids and derived obligatory parasitic trypanosomatids, which belong to the best-studied protists. Due to their omnipresence in aquatic environments and soil, the bodonids are of ecological significance. Here, we present the first global survey of marine kinetoplastids and compare it with the strikingly different patterns of abundance and diversity in their sister clade, the diplonemids. Based on analysis of 18S rDNA V9 ribotypes obtained from 124 sites sampled during the Tara Oceans expedition, our results show generally low to moderate abundance and diversity of planktonic kinetoplastids. Although we have identified all major kinetoplastid lineages, 98% of kinetoplastid reads are represented by neobodonids, namely specimens of the Neobodo and Rhynchomonas genera, which make up 59% and 18% of all reads, respectively. Most kinetoplastids have small cell size (0.8-5 µm) and tend to be more abundant in the mesopelagic as compared to the euphotic zone. Some of the most abundant operational taxonomic units have distinct geographical distributions, and three novel putatively parasitic neobodonids were identified, along with their potential hosts.}, } @article {pmid29266690, year = {2018}, author = {Vader, A and Laughinghouse, HD and Griffiths, C and Jakobsen, KS and Gabrielsen, TM}, title = {Proton-pumping rhodopsins are abundantly expressed by microbial eukaryotes in a high-Arctic fjord.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {890-902}, doi = {10.1111/1462-2920.14035}, pmid = {29266690}, issn = {1462-2920}, abstract = {Proton-pumping rhodopsins provide an alternative pathway to photosynthesis by which solar energy can enter the marine food web. Rhodopsin genes are widely found in marine bacteria, also in the Arctic, and were recently reported from several eukaryotic lineages. So far, little is known about rhodopsin expression in Arctic eukaryotes. In this study, we used metatranscriptomics and 18S rDNA tag sequencing to examine the mid-summer function and composition of marine protists (size 0.45-10 µm) in the high-Arctic Billefjorden (Spitsbergen), especially focussing on the expression of microbial proton-pumping rhodopsins. Rhodopsin transcripts were highly abundant, at a level similar to that of genes involved in photosynthesis. Phylogenetic analyses placed the environmental rhodopsins within disparate eukaryotic lineages, including dinoflagellates, stramenopiles, haptophytes and cryptophytes. Sequence comparison indicated the presence of several functional types, including xanthorhodopsins and a eukaryotic clade of proteorhodopsin. Transcripts belonging to the proteorhodopsin clade were also abundant in published metatranscriptomes from other oceanic regions, suggesting a global distribution. The diversity and abundance of rhodopsins show that these light-driven proton pumps play an important role in Arctic microbial eukaryotes. Understanding this role is imperative to predicting the future of the Arctic marine ecosystem faced by a changing light climate due to diminishing sea-ice.}, } @article {pmid29266683, year = {2018}, author = {Vangchhia, B and Blyton, MDJ and Collignon, P and Kennedy, K and Gordon, DM}, title = {Factors affecting the presence, genetic diversity and antimicrobial sensitivity of Escherichia coli in poultry meat samples collected from Canberra, Australia.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1350-1361}, doi = {10.1111/1462-2920.14030}, pmid = {29266683}, issn = {1462-2920}, abstract = {To investigate the factors determining the clonal composition of Escherichia coli in poultry meat samples, 306 samples were collected from 16 shops, representing three supermarket chains and an independent butchery located in each of the four town centers of Canberra, Australia, during the summer, autumn and winter. A total of 3415 E. coli isolates were recovered and assigned to a phylogenetic group using the Clermont quadruplex PCR method, fingerprinted using repetitive element palindromic (REP) PCR and screened for their antimicrobial susceptibility profiles. The probability of detecting E. coli and the number of fingerprint types detected per sample, as well as the phylogroup membership of the isolates and their antimicrobial sensitivity profiles varied, with one or more of retailer, store, meat type, season and husbandry. The results of this study demonstrate that poultry meat products are likely to be contaminated with a genetically diverse community of E. coli and suggest that factors relating to the nature of the meat product and distribution chain are determinants of the observed diversity.}, } @article {pmid29266662, year = {2018}, author = {Louyakis, AS and Gourlé, H and Casaburi, G and Bonjawo, RME and Duscher, AA and Foster, JS}, title = {A year in the life of a thrombolite: comparative metatranscriptomics reveals dynamic metabolic changes over diel and seasonal cycles.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {842-861}, doi = {10.1111/1462-2920.14029}, pmid = {29266662}, issn = {1462-2920}, abstract = {Microbialites are one of the oldest known ecosystems on Earth and the coordinated metabolisms and activities of these mineral-depositing communities have had a profound impact on the habitability of the planet. Despite efforts to understand the diversity and metabolic potential of these systems, there has not been a systematic molecular analysis of the transcriptional changes that occur within a living microbialite over time. In this study, we generated metatranscriptomic libraries from actively growing thrombolites, a type of microbialite, throughout diel and seasonal cycles and observed dynamic shifts in the population and metabolic transcriptional activity. The most transcribed genes in all seasons were associated with photosynthesis, but only transcripts associated with photosystem II exhibited diel cycling. Photosystem I transcripts were constitutively expressed at all time points including midnight and sunrise. Transcripts associated with nitrogen fixation, methanogenesis and dissimilatory sulfate reduction exhibited diel cycling, and variability between seasons. Networking analysis of the metatranscriptomes showed correlated expression patterns helping to elucidate how metabolic interactions are coordinated within the thrombolite community. These findings have identified distinctive temporal patterns within the thrombolites and will serve an important foundation to understand the mechanisms by which these communities form and respond to changes in their environment.}, } @article {pmid29266651, year = {2018}, author = {Dixit, OVA and O'Brien, CL and Pavli, P and Gordon, DM}, title = {Within-host evolution versus immigration as a determinant of Escherichia coli diversity in the human gastrointestinal tract.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {993-1001}, doi = {10.1111/1462-2920.14028}, pmid = {29266651}, issn = {1462-2920}, abstract = {When a human host harbors two or more strains of Escherichia coli, the second strain is more likely to be a member of the same phylogroup rather than a different phylogroup. This outcome may be the consequence of a within host evolution event or an independent immigration/establishment event. To determine the relative importance of these two events in determining E. coli diversity in a host, a collection of multiple E. coli isolates recovered from each of 67 patients undergoing colonoscopies was used. Whole genome sequence data were available for one example of every REP-fingerprint type identified in a patient. Sequence type (ST) and single-nucleotide polymorphism (SNP) analyses revealed that 83% of strains observed in the host population were a consequence of immigration/establishment events. Restricting the analysis to hosts harboring two or more strains belonging to the same phylogroup revealed that in about half of these cases, the presence of a second strain belonging to the same phylogroup was the consequence of an independent immigration/establishment event. Thus, the results of this study show that despite hosts being exposed to a diversity of E. coli via their food, factors related to the host also determine what E. coli strains succeed in establishing.}, } @article {pmid29266641, year = {2018}, author = {Hamonts, K and Trivedi, P and Garg, A and Janitz, C and Grinyer, J and Holford, P and Botha, FC and Anderson, IC and Singh, BK}, title = {Field study reveals core plant microbiota and relative importance of their drivers.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {124-140}, doi = {10.1111/1462-2920.14031}, pmid = {29266641}, issn = {1462-2920}, abstract = {Harnessing plant microbiota can assist in sustainably increasing primary productivity to meet growing global demands for food and biofuel. However, development of rational microbiome-based approaches for improving crop yield and productivity is currently hindered by a lack of understanding of the major biotic and abiotic factors shaping the crop microbiome under relevant field conditions. We examined bacterial and fungal communities associated with both aerial (leaves, stalks) and belowground (roots, soil) compartments of four commercial sugarcane varieties (Saccharum spp.) grown in several growing regions in Australia. We identified drivers of the sugarcane microbiome under field conditions and evaluated whether the plants shared a core microbiome. Sugarcane-associated microbial assemblages were primarily determined by plant compartment, followed by growing region, crop age, variety and Yellow Canopy Syndrome (YCS). We detected a core set of microbiota and identified members of the core microbiome that were influenced by YCS incidence. Our study revealed key hub microorganisms in the core microbiome networks of sugarcane leaves, stalks, roots and rhizosphere soil despite location and time-associated shifts in the community assemblages. Elucidating their functional roles and identification of the keystone core microbiota that sustain plant health could provide a technological breakthrough for a sustainable increase in crop productivity.}, } @article {pmid29266576, year = {2018}, author = {Cornwall, DH and Kubinak, JL and Zachary, E and Stark, DL and Seipel, D and Potts, WK}, title = {Experimental manipulation of population-level MHC diversity controls pathogen virulence evolution in Mus musculus.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {314-322}, doi = {10.1111/jeb.13225}, pmid = {29266576}, issn = {1420-9101}, support = {R01 GM109500/GM/NIGMS NIH HHS/United States ; }, abstract = {The virulence levels attained by serial passage of pathogens through similar host genotypes are much higher than observed in natural systems; however, it is unknown what keeps natural virulence levels below these empirically demonstrated maximum levels. One hypothesis suggests that host diversity impedes pathogen virulence, because adaptation to one host genotype carries trade-offs in the ability to replicate and cause disease in other host genotypes. To test this hypothesis, with the simplest level of population diversity within the loci of the major histocompatibility complex (MHC), we serially passaged Friend virus complex (FVC) through two rounds, in hosts with either the same MHC genotypes (pure passage) or hosts with different MHC genotypes (alternated passage). Alternated passages showed a significant overall reduction in viral titre (31%) and virulence (54%) when compared to pure passages. Furthermore, a resistant host genotype initially dominated any effects due to MHC diversity; however, when FVC was allowed to adapt to the resistant host genotype, predicted MHC effects emerged; that is, alternated lines show reduced virulence. These data indicate serial exposure to diverse MHC genotypes is an impediment to pathogen adaptation, suggesting genetic variation at MHC loci is important for limiting virulence in a rapidly evolving pathogen and supports negative frequency-dependent selection as a force maintaining MHC diversity in host populations.}, } @article {pmid29266513, year = {2018}, author = {Moody, EK and Lozano-Vilano, ML}, title = {Predation drives morphological convergence in the Gambusia panuco species group among lotic and lentic habitats.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {4}, pages = {491-501}, doi = {10.1111/jeb.13226}, pmid = {29266513}, issn = {1420-9101}, abstract = {Fish morphology is often constrained by a trade-off between optimizing steady vs. unsteady swimming performance due to opposing effects of caudal peduncle size. Lotic environments tend to select for steady swimming performance, leading to smaller caudal peduncles, whereas predators tend to select for unsteady swimming performance, leading to larger caudal peduncles. However, it is unclear which aspect of performance should be optimized across heterogeneous flow and predation environments and how this heterogeneity may affect parallel phenotypic evolution. We investigated this question among four Gambusia species in north-eastern Mexico, specifically the riverine G. panuco, the spring endemics G. alvarezi and G. hurtadoi, and a fourth species, G. marshi, found in a variety of habitats with varying predation pressure in the Cuatro Ciénegas Basin and Río Salado de Nadadores. We employed a geometric morphometric analysis to examine how body shapes of both male and female fish differ among species and habitats and with piscivore presence. We found that high-predation and low-predation species diverged morphologically, with G. marshi exhibiting a variable, intermediate body shape. Within G. marshi, body morphology converged in high-predation environments regardless of flow velocity, and fish from high-predation sites had larger relative caudal peduncle areas. However, we found that G. marshi from low-predation environments diverged in morphology between sub-basins of Cuatro Ciénegas, indicating other differences among these basins that merit further study. Our results suggest that a morphological trade-off promotes parallel evolution of body shape in fishes colonizing high-predation environments and that changing predation pressure can strongly impact morphological evolution in these species.}, } @article {pmid29266503, year = {2018}, author = {Kingston, SE and Martino, P and Melendy, M and Reed, FA and Carlon, DB}, title = {Linking genotype to phenotype in a changing ocean: inferring the genomic architecture of a blue mussel stress response with genome-wide association.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {346-361}, doi = {10.1111/jeb.13224}, pmid = {29266503}, issn = {1420-9101}, abstract = {A key component to understanding the evolutionary response to a changing climate is linking underlying genetic variation to phenotypic variation in stress response. Here, we use a genome-wide association approach (GWAS) to understand the genetic architecture of calcification rates under simulated climate stress. We take advantage of the genomic gradient across the blue mussel hybrid zone (Mytilus edulis and Mytilus trossulus) in the Gulf of Maine (GOM) to link genetic variation with variance in calcification rates in response to simulated climate change. Falling calcium carbonate saturation states are predicted to negatively impact many marine organisms that build calcium carbonate shells - like blue mussels. We sampled wild mussels and measured net calcification phenotypes after exposing mussels to a 'climate change' common garden, where we raised temperature by 3°C, decreased pH by 0.2 units and limited food supply by filtering out planktonic particles >5 μm, compared to ambient GOM conditions in the summer. This climate change exposure greatly increased phenotypic variation in net calcification rates compared to ambient conditions. We then used regression models to link the phenotypic variation with over 170 000 single nucleotide polymorphism loci (SNPs) generated by genotype by sequencing to identify genomic locations associated with calcification phenotype, and estimate heritability and architecture of the trait. We identified at least one of potentially 2-10 genomic regions responsible for 30% of the phenotypic variation in calcification rates that are potential targets of natural selection by climate change. Our simulations suggest a power of 13.7% with our study's average effective sample size of 118 individuals and rare alleles, but a power of >90% when effective sample size is 900.}, } @article {pmid29265998, year = {2018}, author = {Li, Y and Xu, G and Lin, C and Wang, X and Piao, CG}, title = {Aureimonas populi sp. nov., isolated from poplar tree bark.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {487-491}, doi = {10.1099/ijsem.0.002479}, pmid = {29265998}, issn = {1466-5034}, mesh = {Alphaproteobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Plant Bark/*microbiology ; Populus/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Two novel bacterial strains (4M3-2T and 10-107-7) were isolated from poplar tree bark. The strains were Gram-stain-negative facultative aerobes, and produced short rods that were motile because of polar flagella. A phylogenetic tree was reconstructed based on 16S rRNA gene sequences indicating that the two novel strains are related to species of the genus Aureimonas and Aurantimonas. The two novel strains shared the highest 16S rRNA gene sequence similarities with Aureimonasfrigidaquae CW5 7Y-4T (97.1 %) and Aureimonasaltamirensis DSM 21988T (96.6 %)o. The lipids of the novel strain contain diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylcholine and sulfoquinovosyl diacylglycerol. The presence of a distinct glycolipid (sulfoquinovosyl diacylglycerol) is an important chemotaxonomic feature used to distinguish between species of the genera, Aurantimonas and Aureimonas. Additionally, the DNA-DNA hybridization results indicated that the two novel strains represent a novel taxon distinct from Aureimonas frigidaquae. The results of the 16S rRNA gene sequence analysis, as well as the physiological and biochemical characteristics imply that the two novel strains should be assigned to a novel species, with the proposed name Aureimonas populi sp. nov. The type strain is 4M3-2T (=CFCC 11187T=KCTC 42087T).}, } @article {pmid29265369, year = {2018}, author = {Horváth, B and Kalinka, AT}, title = {The genetics of egg retention and fertilization success in Drosophila: One step closer to understanding the transition from facultative to obligate viviparity.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {318-336}, doi = {10.1111/evo.13411}, pmid = {29265369}, issn = {1558-5646}, abstract = {Oviparous, facultative egg retention enables Drosophila females to withhold fertilized eggs in their reproductive tracts until circumstances favor oviposition. The propensity to retain fertilized eggs varies greatly between species, and is correlated with other reproductive traits, such as egg size and ovariole number. While previous studies have described the phenomenon, no study to date has characterized within-species variation or the genetic basis of the trait. Here, we develop a novel microscope-based method for measuring egg retention in Drosophila females and determine the range of phenotypic variation in mated female egg retention in a subset of 91 Drosophila Genetic Reference Panel (DGRP) lines. We inferred the genetic basis of egg retention using a genome-wide association study (GWAS). Further, the scoring of more than 95,000 stained, staged eggs enabled estimates of fertilization success for each line. We found evidence that ovary- and spermathecae-related genes as well as genes affecting olfactory behavior, male mating behavior, male-female attraction and sperm motility may play a crucial role in post-mating physiology. Based on our findings we also propose potential evolutionary routes toward obligate viviparity. In particular, we propose that the loss of fecundity incurred by viviparity could be offset by benefits arising from enhanced mate discrimination, resource specialization, or modified egg morphology.}, } @article {pmid29265367, year = {2018}, author = {Mendelson, TC and Gumm, JM and Martin, MD and Ciccotto, PJ}, title = {Preference for conspecifics evolves earlier in males than females in a sexually dimorphic radiation of fishes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {337-347}, doi = {10.1111/evo.13406}, pmid = {29265367}, issn = {1558-5646}, abstract = {Speciation by sexual selection is generally modeled as the coevolution of female preferences and elaborate male ornaments leading to behavioral (sexual) reproductive isolation. One prediction of these models is that female preference for conspecific males should evolve earlier than male preference for conspecific females in sexually dimorphic species with male ornaments. We tested that prediction in darters, a diverse group of freshwater fishes with sexually dimorphic ornamentation. Focusing on the earliest stages of divergence, we tested preference for conspecific mates in males and females of seven closely related species pairs. Contrary to expectation, male preference for conspecific females was significantly greater than female preference for conspecific males. Males in four of the 14 species significantly preferred conspecific females; whereas, females in no species significantly preferred conspecific males. Relationships between the strength of preference for conspecifics and genetic distance revealed no difference in slope between males and females, but a significant difference in intercept, also suggesting that male preference evolves earlier than females'. Our results are consistent with other recent studies in darters and suggest that the coevolution of female preferences and male ornaments may not best explain the earliest stages of behavioral isolation in this lineage.}, } @article {pmid29264784, year = {2018}, author = {Akhtar, N and Akhtar, K and Ghauri, MA}, title = {Biodesulfurization of Thiophenic Compounds by a 2-Hydroxybiphenyl-Resistant Gordonia sp. HS126-4N Carrying dszABC Genes.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {597-603}, pmid = {29264784}, issn = {1432-0991}, support = {F/5379-1//International Foundation for Science/ ; }, mesh = {Bacterial Proteins/genetics/metabolism ; Biotransformation ; Biphenyl Compounds/*metabolism ; Fossil Fuels/analysis/microbiology ; Gordonia Bacterium/genetics/growth & development/*metabolism ; Mass Spectrometry ; Molecular Structure ; Sulfur/metabolism ; Thiophenes/chemistry/*metabolism ; }, abstract = {Microorganisms can metabolize or transform a range of known chemical compounds present in fossil fuels by naturally having highly specific metabolic activities. In this context, the microbial desulfurization of fuels is an attractive and alternative process to the conventional hydrodesulfurization (HDS) process, since the thiophenic sulfur containing compounds such as dibenzothiophene (DBT) and benzothiophene (BT) cannot be removed by HDS. A DBT desulfurizing mesophilic bacterium, identified on the basis of 16S rRNA gene sequence as Gordonia sp. HS126-4N (source: periphery soil of a coal heap) has been evaluated for its biodesulfurization traits and potential to desulfurize the thiophenic compounds. The HPLC and LC/MS analyses of the metabolites produced from DBT desulfurization and PCR-based nucleotide sequence confirmation of the key desulfurizing genes (dszA/dszB/dszC) proved that HS126-4N could convert DBT to 2-hydroxybiphenyl (2-HBP) via the 4S pathway. The isolate could convert 0.2 mM of DBT to 2-HBP within 48 h and was reasonably tolerant against the inhibitory effect of 2-HBP (retained 70% of growth at 0.5 mM 2-HBP). The isolated biocatalyst desulfurized/degraded 100% of 0.2 mM of 4-methyl DBT, 2,8-dimethyl DBT, BT and 3-methyl BT within 108 h. The capabilities to survive and desulfurize a broad range of thiophenic sulfur containing substrates as well as less inhibition by the 2-HBP suggest that HS126-4N could be a potential candidate for improved biodesulfurization/organic sulfur removal from fossil fuels.}, } @article {pmid29264645, year = {2018}, author = {O'Hanlon, KN and Dam, RA and Archambeault, SL and Berg, CA}, title = {Two Drosophilids exhibit distinct EGF pathway patterns in oogenesis.}, journal = {Development genes and evolution}, volume = {228}, number = {1}, pages = {31-48}, pmid = {29264645}, issn = {1432-041X}, support = {R01 GM079433/GM/NIGMS NIH HHS/United States ; R01-GM079433/NH/NIH HHS/United States ; }, mesh = {Animals ; Body Patterning ; Bone Morphogenetic Proteins/metabolism ; Drosophila Proteins/metabolism ; Drosophila melanogaster/*physiology ; Drosophilidae/classification/*physiology ; Epidermal Growth Factor/metabolism ; Female ; HMGB Proteins/metabolism ; Male ; Oogenesis ; Repressor Proteins/metabolism ; Transcription Factors/metabolism ; Transforming Growth Factor alpha/metabolism ; }, abstract = {Deciphering the evolution of morphological structures is a remaining challenge in the field of developmental biology. The respiratory structures of insect eggshells, called the dorsal appendages, provide an outstanding system for exploring these processes since considerable information is known about their patterning and morphogenesis in Drosophila melanogaster and dorsal appendage number and morphology vary widely across Drosophilid species. We investigated the patterning differences that might facilitate morphogenetic differences between D. melanogaster, which produces two oar-like structures first by wrapping and then elongating the tubes via cell intercalation and cell crawling, and Scaptodrosophila lebanonensis, which produces a variable number of appendages simply by cell intercalation and crawling. Analyses of BMP pathway components thickveins and P-Mad demonstrate that anterior patterning is conserved between these species. In contrast, EGF signaling exhibits significant differences. Transcripts for the ligand encoded by gurken localize similarly in the two species, but this morphogen creates a single dorsolateral primordium in S. lebanonensis as defined by activated MAP kinase and the downstream marker broad. Expression patterns of pointed, argos, and Capicua, early steps in the EGF pathway, exhibit a heterochronic shift in S. lebanonensis relative to those seen in D. melanogaster. We demonstrate that the S. lebanonensis Gurken homolog is active in D. melanogaster but is insufficient to alter downstream patterning responses, indicating that Gurken-EGF receptor interactions do not distinguish the two species' patterning. Altogether, these results differentiate EGF signaling patterns between species and shed light on how changes to the regulation of patterning genes may contribute to different tube-forming mechanisms.}, } @article {pmid29263096, year = {2018}, author = {Wang, J and Saijo, K and Skola, D and Jin, C and Ma, Q and Merkurjev, D and Glass, CK and Rosenfeld, MG}, title = {Histone demethylase LSD1 regulates hematopoietic stem cells homeostasis and protects from death by endotoxic shock.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E244-E252}, pmid = {29263096}, issn = {1091-6490}, support = {R01 CA173903/CA/NCI NIH HHS/United States ; R37 DK039949/DK/NIDDK NIH HHS/United States ; R01 HL065445/HL/NHLBI NIH HHS/United States ; T32 DK007541/DK/NIDDK NIH HHS/United States ; R01 DK018477/DK/NIDDK NIH HHS/United States ; R01 DK039949/DK/NIDDK NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Down-Regulation ; Gene Expression Regulation, Enzymologic ; Hematopoietic Stem Cells/*physiology ; Histone Demethylases/genetics/*metabolism ; Homeostasis/*physiology ; Mice ; Mice, Knockout ; Mice, Transgenic ; MicroRNAs ; Shock, Septic/*pathology ; }, abstract = {Hematopoietic stem cells (HSCs) maintain a quiescent state during homeostasis, but with acute infection, they exit the quiescent state to increase the output of immune cells, the so-called "emergency hematopoiesis." However, HSCs' response to severe infection during septic shock and the pathological impact remain poorly elucidated. Here, we report that the histone demethylase KDM1A/LSD1, serving as a critical regulator of mammalian hematopoiesis, is a negative regulator of the response to inflammation in HSCs during endotoxic shock typically observed during acute bacterial or viral infection. Inflammation-induced LSD1 deficiency results in an acute expansion of a pathological population of hyperproliferative and hyperinflammatory myeloid progenitors, resulting in a septic shock phenotype and acute death. Unexpectedly, in vivo administration of bacterial lipopolysaccharide (LPS) to wild-type mice results in acute suppression of LSD1 in HSCs with a septic shock phenotype that resembles that observed following induced deletion of LSD1 The suppression of LSD1 in HSCs is caused, at least in large part, by a cohort of inflammation-induced microRNAs. Significantly, reconstitution of mice with bone marrow progenitor cells expressing inhibitors of these inflammation-induced microRNAs blocked the suppression of LSD1 in vivo following acute LPS administration and prevented mortality from endotoxic shock. Our results indicate that LSD1 activators or miRNA antagonists could serve as a therapeutic approach for life-threatening septic shock characterized by dysfunction of HSCs.}, } @article {pmid29263095, year = {2018}, author = {Sakavara, A and Tsirtsis, G and Roelke, DL and Mancy, R and Spatharis, S}, title = {Lumpy species coexistence arises robustly in fluctuating resource environments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {4}, pages = {738-743}, pmid = {29263095}, issn = {1091-6490}, mesh = {*Biological Evolution ; Biomass ; Biota/genetics/*physiology ; Competitive Behavior/*physiology ; Ecosystem ; Environment ; Models, Biological ; Natural Resources ; Population Dynamics ; Species Specificity ; }, abstract = {The effect of life-history traits on resource competition outcomes is well understood in the context of a constant resource supply. However, almost all natural systems are subject to fluctuations of resources driven by cyclical processes such as seasonality and tidal hydrology. To understand community composition, it is therefore imperative to study the impact of resource fluctuations on interspecies competition. We adapted a well-established resource-competition model to show that fluctuations in inflow concentrations of two limiting resources lead to the survival of species in clumps along the trait axis, consistent with observations of "lumpy coexistence" [Scheffer M, van Nes EH (2006) Proc Natl Acad Sci USA 103:6230-6235]. A complex dynamic pattern in the available ambient resources arose very early in the self-organization process and dictated the locations of clumps along the trait axis by creating niches that promoted the growth of species with specific traits. This dynamic pattern emerged as the combined result of fluctuations in the inflow of resources and their consumption by the most competitive species that accumulated the bulk of biomass early in assemblage organization. Clumps emerged robustly across a range of periodicities, phase differences, and amplitudes. Given the ubiquity in the real world of asynchronous fluctuations of limiting resources, our findings imply that assemblage organization in clumps should be a common feature in nature.}, } @article {pmid29263094, year = {2018}, author = {Lee, C and Franke, KB and Kamal, SM and Kim, H and Lünsdorf, H and Jäger, J and Nimtz, M and Trček, J and Jänsch, L and Bukau, B and Mogk, A and Römling, U}, title = {Stand-alone ClpG disaggregase confers superior heat tolerance to bacteria.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {E273-E282}, pmid = {29263094}, issn = {1091-6490}, mesh = {*Adaptation, Physiological ; Bacterial Proteins/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; Gene Expression Regulation, Enzymologic ; Gene Transfer, Horizontal ; *Hot Temperature ; Phylogeny ; Pseudomonas aeruginosa/*enzymology/genetics/metabolism ; }, abstract = {AAA+ disaggregases solubilize aggregated proteins and confer heat tolerance to cells. Their disaggregation activities crucially depend on partner proteins, which target the AAA+ disaggregases to protein aggregates while concurrently stimulating their ATPase activities. Here, we report on two potent ClpG disaggregase homologs acquired through horizontal gene transfer by the species Pseudomonas aeruginosa and subsequently abundant P. aeruginosa clone C. ClpG exhibits high, stand-alone disaggregation potential without involving any partner cooperation. Specific molecular features, including high basal ATPase activity, a unique aggregate binding domain, and almost exclusive expression in stationary phase distinguish ClpG from other AAA+ disaggregases. Consequently, ClpG largely contributes to heat tolerance of P. aeruginosa primarily in stationary phase and boosts heat resistance 100-fold when expressed in Escherichia coli This qualifies ClpG as a potential persistence and virulence factor in P. aeruginosa.}, } @article {pmid29261643, year = {2018}, author = {Mooley, KP and Nakar, E and Hotokezaka, K and Hallinan, G and Corsi, A and Frail, DA and Horesh, A and Murphy, T and Lenc, E and Kaplan, DL and De, K and Dobie, D and Chandra, P and Deller, A and Gottlieb, O and Kasliwal, MM and Kulkarni, SR and Myers, ST and Nissanke, S and Piran, T and Lynch, C and Bhalerao, V and Bourke, S and Bannister, KW and Singer, LP}, title = {A mildly relativistic wide-angle outflow in the neutron-star merger event GW170817.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {207-210}, pmid = {29261643}, issn = {1476-4687}, abstract = {GW170817 was the first gravitational-wave detection of a binary neutron-star merger. It was accompanied by radiation across the electromagnetic spectrum and localized to the galaxy NGC 4993 at a distance of 40 megaparsecs. It has been proposed that the observed γ-ray, X-ray and radio emission is due to an ultra-relativistic jet being launched during the merger (and successfully breaking out of the surrounding material), directed away from our line of sight (off-axis). The presence of such a jet is predicted from models that posit neutron-star mergers as the drivers of short hard-γ-ray bursts. Here we report that the radio light curve of GW170817 has no direct signature of the afterglow of an off-axis jet. Although we cannot completely rule out the existence of a jet directed away from the line of sight, the observed γ-ray emission could not have originated from such a jet. Instead, the radio data require the existence of a mildly relativistic wide-angle outflow moving towards us. This outflow could be the high-velocity tail of the neutron-rich material that was ejected dynamically during the merger, or a cocoon of material that breaks out when a jet launched during the merger transfers its energy to the dynamical ejecta. Because the cocoon model explains the radio light curve of GW170817, as well as the γ-ray and X-ray emission (and possibly also the ultraviolet and optical emission), it is the model that is most consistent with the observational data. Cocoons may be a ubiquitous phenomenon produced in neutron-star mergers, giving rise to a hitherto unidentified population of radio, ultraviolet, X-ray and γ-ray transients in the local Universe.}, } @article {pmid29261642, year = {2018}, author = {Saotome, K and Murthy, SE and Kefauver, JM and Whitwam, T and Patapoutian, A and Ward, AB}, title = {Structure of the mechanically activated ion channel Piezo1.}, journal = {Nature}, volume = {554}, number = {7693}, pages = {481-486}, pmid = {29261642}, issn = {1476-4687}, support = {R01 DE022358/DE/NIDCR NIH HHS/United States ; R01 NS083174/NS/NINDS NIH HHS/United States ; S10 OD021634/OD/NIH HHS/United States ; 1-S10OD0211634/NH/NIH HHS/United States ; }, mesh = {Animals ; Binding Sites ; *Cryoelectron Microscopy ; Ion Channel Gating ; Ion Channels/*chemistry/genetics/metabolism/*ultrastructure ; Lipids ; Mice ; Models, Molecular ; Mutation ; Pliability ; Protein Domains ; Solubility ; }, abstract = {Piezo1 and Piezo2 are mechanically activated ion channels that mediate touch perception, proprioception and vascular development. Piezo proteins are distinct from other ion channels and their structure remains poorly defined, which impedes detailed study of their gating and ion permeation properties. Here we report a high-resolution cryo-electron microscopy structure of the mouse Piezo1 trimer. The detergent-solubilized complex adopts a three-bladed propeller shape with a curved transmembrane region containing at least 26 transmembrane helices per protomer. The flexible propeller blades can adopt distinct conformations, and consist of a series of four-transmembrane helical bundles that we term Piezo repeats. Carboxy-terminal domains line the central ion pore, and the channel is closed by constrictions in the cytosol. A kinked helical beam and anchor domain link the Piezo repeats to the pore, and are poised to control gating allosterically. The structure provides a foundation to dissect further how Piezo channels are regulated by mechanical force.}, } @article {pmid29260303, year = {2018}, author = {Xu, X and Liang, K and Niu, Y and Shen, Y and Wan, X and Li, H and Yang, Y}, title = {BAH1 an E3 Ligase from Arabidopsis thaliana Stabilizes Heat Shock Factor σ32 of Escherichia coli by Interacting with DnaK/DnaJ Chaperone Team.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {450-455}, pmid = {29260303}, issn = {1432-0991}, support = {31171586//National Natural Science Foundation of China (CN)/ ; 31271758//National Natural Science Foundation of China/ ; 2015CB755700//National 973 Project/ ; 13480033//Doctoral Starting up Foundation of Henan University of Science and Technology/ ; }, mesh = {Arabidopsis/chemistry/*enzymology/genetics ; Arabidopsis Proteins/chemistry/genetics/*metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; HSP40 Heat-Shock Proteins/genetics/*metabolism ; HSP70 Heat-Shock Proteins/genetics/*metabolism ; Heat-Shock Proteins/genetics/*metabolism ; Molecular Chaperones/genetics/*metabolism ; Protein Binding ; Protein Domains ; Sigma Factor/genetics/*metabolism ; Ubiquitin-Protein Ligases/chemistry/genetics/*metabolism ; }, abstract = {In Escherichia coli, the DnaK/DnaJ chaperone can control the stability and activity of σ32, which is the key factor in heat shock response. Heterologous expression of eukaryotic molecular chaperones protects E. coli from heat stress. Here, we show that BAH1, an E3 ligase from plant that has a similar zinc finger domain to DnaJ, can perform block the effect of DnaK on σ32 in Escherichia coli. By constructing a chimeric DnaJ protein, with the J-domain of DnaJ fused to BAH1, we found BAH1 could partially compensate for the DnaJ' zinc finger domain in vivo, and that it was dependent on the zinc finger domain of BAH1. Furthermore, BAH1 could interact with both σ32 and DnaK to increase the level of HSPs, such as GroEL, DnaK, and σ32. These results suggested that the zinc finger domain was conserved during evolution.}, } @article {pmid29260302, year = {2018}, author = {Saphier, M and Silberstein, E and Shotland, Y and Popov, S and Saphier, O}, title = {Prevalence of Monovalent Copper Over Divalent in Killing Escherichia coli and Staphylococcus aureus.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {426-430}, pmid = {29260302}, issn = {1432-0991}, mesh = {Anti-Infective Agents/chemistry/*pharmacology ; Copper/chemistry/*pharmacology ; Escherichia coli/*drug effects/growth & development ; Microbial Sensitivity Tests ; Microbial Viability/drug effects ; Silver/pharmacology ; Staphylococcus aureus/*drug effects/growth & development ; }, abstract = {This study opens the investigation series focused on antimicrobial effects of copper (Cu) compared to silver (Ag), which is currently used to treat wound infection in burn victims as well as in chronic wounds. Noticeably, in its ionized state, Cu is more commonly present as Cu2+ rather than as Cu+, while electronic configuration similarity of Cu+ and Ag+ indicates that actually it may be the active state. To test this hypothesis, effect of Cu+ and Cu2+, using Ag+ ions and metallic copper as controls on Escherichia coli and Staphylococcus aureus bacteria, was examined under anaerobic conditions. Cu+ was produced by two different methods, and its effect on microorganism growth was tested using a syringe and Petri dish methods. It was found that the presence of Cu+ causes a dramatic depletion in the viability of both microorganisms. Metallic copper did not have any effect on the viability, whereas Cu2+ and Ag+ ions had much lower activity than Cu+ ions. Minimal inhibitory concentration of Cu+ for E. coli was twice lower than that of Cu2+. The obtained results show that Cu+ proves to be a potent antimicrobial agent.}, } @article {pmid29260254, year = {2018}, author = {Böttcher, T}, title = {From Molecules to Life: Quantifying the Complexity of Chemical and Biological Systems in the Universe.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {1-10}, pmid = {29260254}, issn = {1432-1432}, support = {Emmy Noether//DFG/ ; Marie Curie Zukunftskolleg Incoming Fellowship//EU FP7/ ; }, abstract = {Life is a complex phenomenon and much research has been devoted to both understanding its origins from prebiotic chemistry and discovering life beyond Earth. Yet, it has remained elusive how to quantify this complexity and how to compare chemical and biological units on one common scale. Here, a mathematical description of molecular complexity was applied allowing to quantitatively assess complexity of chemical structures. This in combination with the orthogonal measure of information complexity resulted in a two-dimensional complexity space ranging over the entire spectrum from molecules to organisms. Entities with a certain level of information complexity directly require a functionally complex mechanism for their production or replication and are hence indicative for life-like systems. In order to describe entities combining molecular and information complexity, the term biogenic unit was introduced. Exemplified biogenic unit complexities were calculated for ribozymes, protein enzymes, multimeric protein complexes, and even an entire virus particle. Complexities of prokaryotic and eukaryotic cells, as well as multicellular organisms, were estimated. Thereby distinct evolutionary stages in complexity space were identified. The here developed approach to compare the complexity of biogenic units allows for the first time to address the gradual characteristics of prebiotic and life-like systems without the need for a definition of life. This operational concept may guide our search for life in the Universe, and it may direct the investigations of prebiotic trajectories that lead towards the evolution of complexity at the origins of life.}, } @article {pmid29259121, year = {2018}, author = {Walley, JW and Shen, Z and McReynolds, MR and Schmelz, EA and Briggs, SP}, title = {Fungal-induced protein hyperacetylation in maize identified by acetylome profiling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {210-215}, pmid = {29259121}, issn = {1091-6490}, support = {F32 GM096707/GM/NIGMS NIH HHS/United States ; }, mesh = {Acetylation ; *Ascomycota/immunology ; Peptides, Cyclic/*immunology ; *Plant Diseases/immunology/microbiology ; Plant Proteins/*immunology ; *Zea mays/immunology/microbiology ; }, abstract = {Lysine acetylation is a key posttranslational modification that regulates diverse proteins involved in a range of biological processes. The role of histone acetylation in plant defense is well established, and it is known that pathogen effector proteins encoding acetyltransferases can directly acetylate host proteins to alter immunity. However, it is unclear whether endogenous plant enzymes can modulate protein acetylation during an immune response. Here, we investigate how the effector molecule HC-toxin (HCT), a histone deacetylase inhibitor produced by the fungal pathogen Cochliobolus carbonum race 1, promotes virulence in maize through altering protein acetylation. Using mass spectrometry, we globally quantified the abundance of 3,636 proteins and the levels of acetylation at 2,791 sites in maize plants treated with HCT as well as HCT-deficient or HCT-producing strains of C. carbonum Analyses of these data demonstrate that acetylation is a widespread posttranslational modification impacting proteins encoded by many intensively studied maize genes. Furthermore, the application of exogenous HCT enabled us to show that the activity of plant-encoded enzymes (histone deacetylases) can be modulated to alter acetylation of nonhistone proteins during an immune response. Collectively, these results provide a resource for further mechanistic studies examining the regulation of protein function by reversible acetylation and offer insight into the complex immune response triggered by virulent C. carbonum.}, } @article {pmid29259120, year = {2018}, author = {Granold, M and Hajieva, P and Toşa, MI and Irimie, FD and Moosmann, B}, title = {Modern diversification of the amino acid repertoire driven by oxygen.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {41-46}, pmid = {29259120}, issn = {1091-6490}, mesh = {Amino Acids/*chemistry ; *Models, Chemical ; *Origin of Life ; Oxygen/*chemistry ; }, abstract = {All extant life employs the same 20 amino acids for protein biosynthesis. Studies on the number of amino acids necessary to produce a foldable and catalytically active polypeptide have shown that a basis set of 7-13 amino acids is sufficient to build major structural elements of modern proteins. Hence, the reasons for the evolutionary selection of the current 20 amino acids out of a much larger available pool have remained elusive. Here, we have analyzed the quantum chemistry of all proteinogenic and various prebiotic amino acids. We find that the energetic HOMO-LUMO gap, a correlate of chemical reactivity, becomes incrementally closer in modern amino acids, reaching the level of specialized redox cofactors in the late amino acids tryptophan and selenocysteine. We show that the arising prediction of a higher reactivity of the more recently added amino acids is correct as regards various free radicals, particularly oxygen-derived peroxyl radicals. Moreover, we demonstrate an immediate survival benefit conferred by the enhanced redox reactivity of the modern amino acids tyrosine and tryptophan in oxidatively stressed cells. Our data indicate that in demanding building blocks with more versatile redox chemistry, biospheric molecular oxygen triggered the selective fixation of the last amino acids in the genetic code. Thus, functional rather than structural amino acid properties were decisive during the finalization of the universal genetic code.}, } @article {pmid29259119, year = {2018}, author = {Trevers, KE and Prajapati, RS and Hintze, M and Stower, MJ and Strobl, AC and Tambalo, M and Ranganathan, R and Moncaut, N and Khan, MAF and Stern, CD and Streit, A}, title = {Neural induction by the node and placode induction by head mesoderm share an initial state resembling neural plate border and ES cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {355-360}, pmid = {29259119}, issn = {1091-6490}, support = {513:KCL:AS//Action on Hearing Loss/United Kingdom ; G0400559//Medical Research Council/United Kingdom ; R01 DC011577/DC/NIDCD NIH HHS/United States ; R01 DE022065/DE/NIDCR NIH HHS/United States ; BB/K007742/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Central Nervous System/embryology/*metabolism ; Chick Embryo ; *Embryonic Induction ; Embryonic Stem Cells/*metabolism ; Gastrula/embryology/*metabolism ; Gene Expression Profiling/methods ; Gene Expression Regulation, Developmental ; In Situ Hybridization ; Mesoderm/embryology/*metabolism ; Neural Plate/embryology/*metabolism ; }, abstract = {Around the time of gastrulation in higher vertebrate embryos, inductive interactions direct cells to form central nervous system (neural plate) or sensory placodes. Grafts of different tissues into the periphery of a chicken embryo elicit different responses: Hensen's node induces a neural plate whereas the head mesoderm induces placodes. How different are these processes? Transcriptome analysis in time course reveals that both processes start by induction of a common set of genes, which later diverge. These genes are remarkably similar to those induced by an extraembryonic tissue, the hypoblast, and are normally expressed in the pregastrulation stage epiblast. Explants of this epiblast grown in the absence of further signals develop as neural plate border derivatives and eventually express lens markers. We designate this state as "preborder"; its transcriptome resembles embryonic stem cells. Finally, using sequential transplantation experiments, we show that the node, head mesoderm, and hypoblast are interchangeable to begin any of these inductions while the final outcome depends on the tissue emitting the later signals.}, } @article {pmid29259118, year = {2018}, author = {Li, X and Yu, B and Sun, Q and Zhang, Y and Ren, M and Zhang, X and Li, A and Yuan, J and Madisen, L and Luo, Q and Zeng, H and Gong, H and Qiu, Z}, title = {Generation of a whole-brain atlas for the cholinergic system and mesoscopic projectome analysis of basal forebrain cholinergic neurons.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {415-420}, pmid = {29259118}, issn = {1091-6490}, mesh = {Animals ; Basal Forebrain/anatomy & histology/*cytology/diagnostic imaging ; Brain/anatomy & histology/*cytology/diagnostic imaging ; Cell Count ; Cerebral Cortex/anatomy & histology/*cytology/diagnostic imaging ; Cholinergic Neurons/*cytology ; Mesencephalon/anatomy & histology/cytology/diagnostic imaging ; Mice ; Models, Anatomic ; }, abstract = {The cholinergic system in the brain plays crucial roles in regulating sensory and motor functions as well as cognitive behaviors by modulating neuronal activity. Understanding the organization of the cholinergic system requires a complete map of cholinergic neurons and their axon arborizations throughout the entire brain at the level of single neurons. Here, we report a comprehensive whole-brain atlas of the cholinergic system originating from various cortical and subcortical regions of the mouse brain. Using genetically labeled cholinergic neurons together with whole-brain reconstruction of optical images at 2-μm resolution, we obtained quantification of the number and soma volume of cholinergic neurons in 22 brain areas. Furthermore, by reconstructing the complete axonal arbors of fluorescently labeled single neurons from a subregion of the basal forebrain at 1-μm resolution, we found that their projections to the forebrain and midbrain showed neuronal subgroups with distinct projection specificity and diverse arbor distribution within the same projection area. These results suggest the existence of distinct subtypes of cholinergic neurons that serve different regulatory functions in the brain and illustrate the usefulness of complete reconstruction of neuronal distribution and axon projections at the mesoscopic level.}, } @article {pmid29259116, year = {2018}, author = {van der Zwan, A and Bi, K and Norwitz, ER and Crespo, ÂC and Claas, FHJ and Strominger, JL and Tilburgs, T}, title = {Mixed signature of activation and dysfunction allows human decidual CD8+ T cells to provide both tolerance and immunity.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {385-390}, pmid = {29259116}, issn = {1091-6490}, support = {R01 AI053330/AI/NIAID NIH HHS/United States ; R56 AI053330/AI/NIAID NIH HHS/United States ; }, mesh = {CD8-Positive T-Lymphocytes/immunology/*metabolism ; Cytomegalovirus/immunology/physiology ; Cytomegalovirus Infections/genetics/immunology/virology ; Decidua/*metabolism ; Female ; Gene Expression Profiling/*methods ; Granzymes/genetics/metabolism ; Humans ; Immune Tolerance/*genetics/immunology ; Lymphocyte Activation/genetics/immunology ; Perforin/genetics/metabolism ; Time Factors ; }, abstract = {Understanding how decidual CD8+ T cell (CD8+ dT) cytotoxicity is regulated and how these cells integrate the competing needs for maternal-fetal tolerance and immunity to infection is an important research and clinical goal. Gene-expression analysis of effector-memory CD8+ dT demonstrated a mixed transcriptional signature of T cell dysfunction, activation, and effector function. High protein expression of coinhibitory molecules PD1, CTLA4, and LAG3, accompanied by low expression of cytolytic molecules suggests that the decidual microenvironment reduces CD8+ dT effector responses to maintain tolerance to fetal antigens. However, CD8+ dT degranulated, proliferated, and produced IFN-γ, TNF-α, perforin, and granzymes upon in vitro stimulation, demonstrating that CD8+ dT are not permanently suppressed and retain the capacity to respond to proinflammatory events, such as infections. The balance between transient dysfunction of CD8+ dT that are permissive of placental and fetal development, and reversal of this dysfunctional state, is crucial in understanding the etiology of pregnancy complications and prevention of congenital infections.}, } @article {pmid29259115, year = {2018}, author = {Lipper, CH and Karmi, O and Sohn, YS and Darash-Yahana, M and Lammert, H and Song, L and Liu, A and Mittler, R and Nechushtai, R and Onuchic, JN and Jennings, PA}, title = {Structure of the human monomeric NEET protein MiNT and its role in regulating iron and reactive oxygen species in cancer cells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {272-277}, pmid = {29259115}, issn = {1091-6490}, support = {R01 GM101467/GM/NIGMS NIH HHS/United States ; }, mesh = {Cell Line, Tumor ; Crystallography, X-Ray ; Humans ; Iron/*metabolism ; Iron-Sulfur Proteins/chemistry/genetics/*metabolism ; Kinetics ; Mitochondrial Membranes/metabolism ; Mitochondrial Proteins/chemistry/genetics/*metabolism ; Molecular Dynamics Simulation ; Mutation ; Neoplasms/genetics/metabolism/pathology ; Protein Domains ; Protein Folding ; RNA Interference ; Reactive Oxygen Species/*metabolism ; }, abstract = {The NEET family is a relatively new class of three related [2Fe-2S] proteins (CISD1-3), important in human health and disease. While there has been growing interest in the homodimeric gene products of CISD1 (mitoNEET) and CISD2 (NAF-1), the importance of the inner mitochondrial CISD3 protein has only recently been recognized in cancer. The CISD3 gene encodes for a monomeric protein that contains two [2Fe-2S] CDGSH motifs, which we term mitochondrial inner NEET protein (MiNT). It folds with a pseudosymmetrical fold that provides a hydrophobic motif on one side and a relatively hydrophilic surface on the diametrically opposed surface. Interestingly, as shown by molecular dynamics simulation, the protein displays distinct asymmetrical backbone motions, unlike its homodimeric counterparts that face the cytosolic side of the outer mitochondrial membrane/endoplasmic reticulum (ER). However, like its counterparts, our biological studies indicate that knockdown of MiNT leads to increased accumulation of mitochondrial labile iron, as well as increased mitochondrial reactive oxygen production. Taken together, our study suggests that the MiNT protein functions in the same pathway as its homodimeric counterparts (mitoNEET and NAF-1), and could be a key player in this pathway within the mitochondria. As such, it represents a target for anticancer or antidiabetic drug development.}, } @article {pmid29259114, year = {2018}, author = {Jaffe, AM and Liu, Z}, title = {Mathematical picture language program.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {81-86}, pmid = {29259114}, issn = {1091-6490}, abstract = {We give an overview of our philosophy of pictures in mathematics. We emphasize a bidirectional process between picture language and mathematical concepts: abstraction and simulation. This motivates a program to understand different subjects, using virtual and real mathematical concepts simulated by pictures.}, } @article {pmid29259113, year = {2018}, author = {Li, X and Jusup, M and Wang, Z and Li, H and Shi, L and Podobnik, B and Stanley, HE and Havlin, S and Boccaletti, S}, title = {Punishment diminishes the benefits of network reciprocity in social dilemma experiments.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {30-35}, pmid = {29259113}, issn = {1091-6490}, mesh = {*Cooperative Behavior ; Female ; Humans ; Male ; *Models, Theoretical ; *Punishment ; *Social Support ; }, abstract = {Network reciprocity has been widely advertised in theoretical studies as one of the basic cooperation-promoting mechanisms, but experimental evidence favoring this type of reciprocity was published only recently. When organized in an unchanging network of social contacts, human subjects cooperate provided the following strict condition is satisfied: The benefit of cooperation must outweigh the total cost of cooperating with all neighbors. In an attempt to relax this condition, we perform social dilemma experiments wherein network reciprocity is aided with another theoretically hypothesized cooperation-promoting mechanism-costly punishment. The results reveal how networks promote and stabilize cooperation. This stabilizing effect is stronger in a smaller-size neighborhood, as expected from theory and experiments. Contrary to expectations, punishment diminishes the benefits of network reciprocity by lowering assortment, payoff per round, and award for cooperative behavior. This diminishing effect is stronger in a larger-size neighborhood. An immediate implication is that the psychological effects of enduring punishment override the rational response anticipated in quantitative models of cooperation in networks.}, } @article {pmid29259112, year = {2018}, author = {Ragone, F and Wouters, J and Bouchet, F}, title = {Computation of extreme heat waves in climate models using a large deviation algorithm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {24-29}, pmid = {29259112}, issn = {1091-6490}, abstract = {Studying extreme events and how they evolve in a changing climate is one of the most important current scientific challenges. Starting from complex climate models, a key difficulty is to be able to run long enough simulations to observe those extremely rare events. In physics, chemistry, and biology, rare event algorithms have recently been developed to compute probabilities of events that cannot be observed in direct numerical simulations. Here we propose such an algorithm, specifically designed for extreme heat or cold waves, based on statistical physics. This approach gives an improvement of more than two orders of magnitude in the sampling efficiency. We describe the dynamics of events that would not be observed otherwise. We show that European extreme heat waves are related to a global teleconnection pattern involving North America and Asia. This tool opens up a wide range of possible studies to quantitatively assess the impact of climate change.}, } @article {pmid29259111, year = {2018}, author = {Chalk, M and Marre, O and Tkačik, G}, title = {Toward a unified theory of efficient, predictive, and sparse coding.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {186-191}, pmid = {29259111}, issn = {1091-6490}, support = {U01 NS090501/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Humans ; *Models, Neurological ; Sensory Receptor Cells/*physiology ; }, abstract = {A central goal in theoretical neuroscience is to predict the response properties of sensory neurons from first principles. To this end, "efficient coding" posits that sensory neurons encode maximal information about their inputs given internal constraints. There exist, however, many variants of efficient coding (e.g., redundancy reduction, different formulations of predictive coding, robust coding, sparse coding, etc.), differing in their regimes of applicability, in the relevance of signals to be encoded, and in the choice of constraints. It is unclear how these types of efficient coding relate or what is expected when different coding objectives are combined. Here we present a unified framework that encompasses previously proposed efficient coding models and extends to unique regimes. We show that optimizing neural responses to encode predictive information can lead them to either correlate or decorrelate their inputs, depending on the stimulus statistics; in contrast, at low noise, efficiently encoding the past always predicts decorrelation. Later, we investigate coding of naturalistic movies and show that qualitatively different types of visual motion tuning and levels of response sparsity are predicted, depending on whether the objective is to recover the past or predict the future. Our approach promises a way to explain the observed diversity of sensory neural responses, as due to multiple functional goals and constraints fulfilled by different cell types and/or circuits.}, } @article {pmid29259110, year = {2018}, author = {Eriksen, RS and Svenningsen, SL and Sneppen, K and Mitarai, N}, title = {A growing microcolony can survive and support persistent propagation of virulent phages.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {337-342}, pmid = {29259110}, issn = {1091-6490}, mesh = {Bacterial Load ; Bacterial Physiological Phenomena ; Bacteriophage P1/genetics/*pathogenicity ; Ecosystem ; Escherichia coli/genetics/*growth & development/*virology ; Host-Pathogen Interactions ; Microbial Viability/genetics ; Mutation ; Quorum Sensing/genetics ; Virulence/genetics ; }, abstract = {Bacteria form colonies and secrete extracellular polymeric substances that surround the individual cells. These spatial structures are often associated with collaboration and quorum sensing between the bacteria. Here we investigate the mutual protection provided by spherical growth of a monoclonal colony during exposure to phages that proliferate on its surface. As a proof of concept we exposed growing colonies of Escherichia coli to a virulent mutant of phage P1. When the colony consists of less than [Formula: see text]50,000 members it is eliminated, while larger initial colonies allow long-term survival of both phage-resistant mutants and, importantly, colonies of mostly phage-sensitive members. A mathematical model predicts that colonies formed solely by phage-sensitive bacteria can survive because the growth of bacteria throughout the colony exceeds the killing of bacteria on the surface and pinpoints how the critical colony size depends on key parameters in the phage infection cycle.}, } @article {pmid29259109, year = {2018}, author = {Balthazart, J}, title = {Fraternal birth order effect on sexual orientation explained.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {234-236}, pmid = {29259109}, issn = {1091-6490}, mesh = {*Birth Order ; *Sexual Behavior ; }, } @article {pmid29259108, year = {2018}, author = {Yao, NY and O'Donnell, ME}, title = {Replication fork convergence at termination: A multistep process.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {237-239}, pmid = {29259108}, issn = {1091-6490}, support = {R01 GM115809/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {DNA Helicases ; *DNA Replication ; *Genomic Instability ; Humans ; }, } @article {pmid29259107, year = {2018}, author = {Bausch, J and Cubitt, TS and Lucia, A and Perez-Garcia, D and Wolf, MM}, title = {Size-driven quantum phase transitions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {19-23}, pmid = {29259107}, issn = {1091-6490}, abstract = {Can the properties of the thermodynamic limit of a many-body quantum system be extrapolated by analyzing a sequence of finite-size cases? We present models for which such an approach gives completely misleading results: translationally invariant, local Hamiltonians on a square lattice with open boundary conditions and constant spectral gap, which have a classical product ground state for all system sizes smaller than a particular threshold size, but a ground state with topological degeneracy for all system sizes larger than this threshold. Starting from a minimal case with spins of dimension 6 and threshold lattice size [Formula: see text], we show that the latter grows faster than any computable function with increasing local spin dimension. The resulting effect may be viewed as a unique type of quantum phase transition that is driven by the size of the system rather than by an external field or coupling strength. We prove that the construction is thermally robust, showing that these effects are in principle accessible to experimental observation.}, } @article {pmid29258880, year = {2018}, author = {Schön, I and Higuti, J and Patel, T and Martens, K}, title = {Aquatic long-distance dispersal and vicariance shape the evolution of an ostracod species complex (Crustacea) in four major Brazilian floodplains.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {86-97}, doi = {10.1016/j.ympev.2017.12.019}, pmid = {29258880}, issn = {1095-9513}, mesh = {Animal Migration/*physiology ; Animals ; Aquatic Organisms/*physiology ; Bayes Theorem ; Brazil ; Crustacea/*anatomy & histology/*physiology ; Electron Transport Complex IV/genetics ; Evolution, Molecular ; Genetic Speciation ; Geography ; Paraguay ; Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Cladogenesis is often driven by the interplay of dispersal and vicariance. The importance of long-distance dispersal in biogeography and speciation is increasingly recognised, but still ill-understood. Here, we study faunal interconnectivity between four large Brazilian floodplains, namely the Amazon, Araguaia, Pantanal (on Paraguay River) and Upper Paraná River floodplains, investigating a species complex of the non-marine ostracod genus Strandesia. We use DNA sequence data from the mitochondrial COI and the nuclear Elongation Factor 1 alpha genes to construct molecular phylogenies and minimum spanning networks, to identify genetic species, analyse biogeographic histories and provide preliminary age estimates of this species complex. The Strandesia species complex includes five morphological and eleven genetic species, which doubles the known diversity in this lineage. The evolutionary history of this species complex appears to comprise sequences of dispersal and vicariance events. Faunal and genetic patterns of connectivity between floodplains in some genetic species are mirrored in modern hydrological connections. This could explain why we find evidence for (aquatic) long-distance dispersal between floodplains, thousands of kilometres apart. Our phylogenetic reconstructions seem to mostly indicate recent dispersal and vicariance events, but the evolution of the present Strandesia species complex could span up to 25 Myr, which by far exceeds the age of the floodplains and the rivers in their current forms.}, } @article {pmid29258879, year = {2018}, author = {Guerra, D and Bouvet, K and Breton, S}, title = {Mitochondrial gene order evolution in Mollusca: Inference of the ancestral state from the mtDNA of Chaetopleura apiculata (Polyplacophora, Chaetopleuridae).}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {233-239}, doi = {10.1016/j.ympev.2017.12.013}, pmid = {29258879}, issn = {1095-9513}, mesh = {Animals ; DNA, Mitochondrial/chemistry/genetics/metabolism ; *Evolution, Molecular ; Gene Order ; *Genome, Mitochondrial ; High-Throughput Nucleotide Sequencing ; Phylogeny ; Polyplacophora/classification/*genetics ; Sequence Analysis, DNA ; }, abstract = {The mitochondrial genome architecture of polyplacophorans has been usually regarded as being very ancient in comparison to all mollusks. However, even if some complete chiton mtDNAs have been recently sequenced, thorough studies of their evolution are lacking. To further expand the set of complete chiton mtDNAs and perform such analysis, we sequenced the mitochondrial genome of the Eastern beaded chiton Chaetopleura apiculata (Chaetopleuridae) using next-generation sequencing. With mitochondrial sequences from all available chiton mtDNAs, we also built a phylogeny on which we reconstructed the evolution of gene arrangement in this class. The arrangement of C. apiculata proved to be the most primitive known so far for polyplacophorans. Comparing this gene order to those of other molluscan classes, we found that it most probably is the original gene order of the last common ancestor to all extant Mollusca. The ancient mitochondrial genome organization of C. apiculata is an important information that may help reconstructing the phylogeny of Mollusca and their relationship with other lophotrochozoans.}, } @article {pmid29258872, year = {2018}, author = {Goodson, NB and Nahreini, J and Randazzo, G and Uruena, A and Johnson, JE and Brzezinski, JA}, title = {Prdm13 is required for Ebf3+ amacrine cell formation in the retina.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {149-163}, pmid = {29258872}, issn = {1095-564X}, support = {R01 EY024272/EY/NEI NIH HHS/United States ; R01 HD037932/HD/NICHD NIH HHS/United States ; R37 HD091856/HD/NICHD NIH HHS/United States ; }, mesh = {Amacrine Cells/cytology/*metabolism ; Animals ; Apoptosis/*physiology ; Calbindin 2/biosynthesis/genetics ; Cell Survival/physiology ; Gene Expression Regulation, Developmental/*physiology ; Histone-Lysine N-Methyltransferase/*biosynthesis/genetics ; Mice ; Mice, Transgenic ; Stem Cells/cytology/*metabolism ; Transcription Factors/*biosynthesis/genetics ; }, abstract = {Amacrine interneurons play a critical role in the processing of visual signals within the retina. They are highly diverse, representing 30 or more distinct subtypes. Little is known about how amacrine subtypes acquire their unique gene expression and morphological features. We characterized the gene expression pattern of the zinc-finger transcription factor Prdm13 in the mouse. Consistent with a developmental role, Prdm13 was expressed by Ptf1a+ amacrine and horizontal precursors. Over time, Prdm13 expression diverged from the transiently expressed Ptf1a and marked just a subset of amacrine cells in the adult retina. While heterogeneous, we show that most of these Prdm13+ amacrine cells express the transcription factor Ebf3 and the calcium binding protein calretinin. Loss of Prdm13 did not affect the number of amacrine cells formed during development. However, we observed a modest loss of amacrine cells and increased apoptosis that correlated with the onset timing of Ebf3 expression. Adult Prdm13 loss-of-function mice had 25% fewer amacrine cells, altered calretinin expression, and a lack of Ebf3+ amacrines. Forcing Prdm13 expression in retinal progenitor cells did not significantly increase amacrine cell formation, Ebf3 or calretinin expression, and appeared detrimental to the survival of photoreceptors. Our data show that Prdm13 is not required for amacrine fate as a class, but is essential for the formation of Ebf3+ amacrine cell subtypes. Rather than driving subtype identity, Prdm13 may act by restricting competing fate programs to maintain identity and survival.}, } @article {pmid29258714, year = {2018}, author = {Thomson, NM and Rossmann, FM and Ferreira, JL and Matthews-Palmer, TR and Beeby, M and Pallen, MJ}, title = {Bacterial Flagellins: Does Size Matter?.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {575-581}, doi = {10.1016/j.tim.2017.11.010}, pmid = {29258714}, issn = {1878-4380}, support = {MR/L015080/1//Medical Research Council/United Kingdom ; }, abstract = {The bacterial flagellum is the principal organelle of motility in bacteria. Here, we address the question of size when applied to the chief flagellar protein flagellin and the flagellar filament. Surprisingly, nature furnishes multiple examples of 'giant flagellins' greater than a thousand amino acids in length, with large surface-exposed hypervariable domains. We review the contexts in which these giant flagellins occur, speculate as to their functions, and highlight the potential for biotechnology to build on what nature provides.}, } @article {pmid29258300, year = {2018}, author = {Bourrier, V and Lovis, C and Beust, H and Ehrenreich, D and Henry, GW and Astudillo-Defru, N and Allart, R and Bonfils, X and Ségransan, D and Delfosse, X and Cegla, HM and Wyttenbach, A and Heng, K and Lavie, B and Pepe, F}, title = {Orbital misalignment of the Neptune-mass exoplanet GJ 436b with the spin of its cool star.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {477-480}, pmid = {29258300}, issn = {1476-4687}, abstract = {The angle between the spin of a star and the orbital planes of its planets traces the history of the planetary system. Exoplanets orbiting close to cool stars are expected to be on circular, aligned orbits because of strong tidal interactions with the stellar convective envelope. Spin-orbit alignment can be measured when the planet transits its star, but such ground-based spectroscopic measurements are challenging for cool, slowly rotating stars. Here we report the three-dimensional characterization of the trajectory of an exoplanet around an M dwarf star, derived by mapping the spectrum of the stellar photosphere along the chord transited by the planet. We find that the eccentric orbit of the Neptune-mass exoplanet GJ 436b is nearly perpendicular to the stellar equator. Both eccentricity and misalignment, surprising around a cool star, can result from dynamical interactions (via Kozai migration) with a yet-undetected outer companion. This inward migration of GJ 436b could have triggered the atmospheric escape that now sustains its giant exosphere.}, } @article {pmid29258299, year = {2018}, author = {Wang, Y and Small, DL and Stanimirovic, DB and Morley, P and Durkin, JP}, title = {Corrigendum: AMPA receptor-mediated regulation of a Gi-protein in cortical neurons.}, journal = {Nature}, volume = {554}, number = {7692}, pages = {392}, pmid = {29258299}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/39062.}, } @article {pmid29258298, year = {2018}, author = {Paladini, C and Baron, F and Jorissen, A and Le Bouquin, JB and Freytag, B and Van Eck, S and Wittkowski, M and Hron, J and Chiavassa, A and Berger, JP and Siopis, C and Mayer, A and Sadowski, G and Kravchenko, K and Shetye, S and Kerschbaum, F and Kluska, J and Ramstedt, S}, title = {Large granulation cells on the surface of the giant star π1 Gruis.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {310-312}, doi = {10.1038/nature25001}, pmid = {29258298}, issn = {1476-4687}, abstract = {Convection plays a major part in many astrophysical processes, including energy transport, pulsation, dynamos and winds on evolved stars, in dust clouds and on brown dwarfs. Most of our knowledge about stellar convection has come from studying the Sun: about two million convective cells with typical sizes of around 2,000 kilometres across are present on the surface of the Sun-a phenomenon known as granulation. But on the surfaces of giant and supergiant stars there should be only a few large (several tens of thousands of times larger than those on the Sun) convective cells, owing to low surface gravity. Deriving the characteristic properties of convection (such as granule size and contrast) for the most evolved giant and supergiant stars is challenging because their photospheres are obscured by dust, which partially masks the convective patterns. These properties can be inferred from geometric model fitting, but this indirect method does not provide information about the physical origin of the convective cells. Here we report interferometric images of the surface of the evolved giant star π1 Gruis, of spectral type S5,7. Our images show a nearly circular, dust-free atmosphere, which is very compact and only weakly affected by molecular opacity. We find that the stellar surface has a complex convective pattern with an average intensity contrast of 12 per cent, which increases towards shorter wavelengths. We derive a characteristic horizontal granule size of about 1.2 × 1011 metres, which corresponds to 27 per cent of the diameter of the star. Our measurements fall along the scaling relations between granule size, effective temperature and surface gravity that are predicted by simulations of stellar surface convection.}, } @article {pmid29258297, year = {2018}, author = {Gao, X and Tao, Y and Lamas, V and Huang, M and Yeh, WH and Pan, B and Hu, YJ and Hu, JH and Thompson, DB and Shu, Y and Li, Y and Wang, H and Yang, S and Xu, Q and Polley, DB and Liberman, MC and Kong, WJ and Holt, JR and Chen, ZY and Liu, DR}, title = {Treatment of autosomal dominant hearing loss by in vivo delivery of genome editing agents.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {217-221}, pmid = {29258297}, issn = {1476-4687}, support = {F32 DC000138/DC/NIDCD NIH HHS/United States ; R01 DC000188/DC/NIDCD NIH HHS/United States ; R01 DC009836/DC/NIDCD NIH HHS/United States ; R35 GM118062/GM/NIGMS NIH HHS/United States ; R01 DC013521/DC/NIDCD NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; U54 HD090255/HD/NICHD NIH HHS/United States ; P30 DC005209/DC/NIDCD NIH HHS/United States ; R01 DC006908/DC/NIDCD NIH HHS/United States ; R01 EB022376/EB/NIBIB NIH HHS/United States ; }, mesh = {Acoustic Stimulation ; Alleles ; Animals ; Animals, Newborn ; Auditory Threshold ; Base Sequence ; CRISPR-Associated Proteins/*administration & dosage/metabolism/therapeutic use ; CRISPR-Cas Systems ; Cell Survival ; Cochlea/cytology/metabolism ; Disease Models, Animal ; Evoked Potentials, Auditory, Brain Stem ; Female ; Fibroblasts ; Gene Editing/*methods ; Genes, Dominant/*genetics ; Genetic Therapy/*methods ; Hair Cells, Auditory/cytology ; Hearing Loss/*genetics/physiopathology/prevention & control ; Humans ; Liposomes ; Male ; Membrane Proteins/genetics ; Mice ; Reflex, Startle ; }, abstract = {Although genetic factors contribute to almost half of all cases of deafness, treatment options for genetic deafness are limited. We developed a genome-editing approach to target a dominantly inherited form of genetic deafness. Here we show that cationic lipid-mediated in vivo delivery of Cas9-guide RNA complexes can ameliorate hearing loss in a mouse model of human genetic deafness. We designed and validated, both in vitro and in primary fibroblasts, genome editing agents that preferentially disrupt the dominant deafness-associated allele in the Tmc1 (transmembrane channel-like gene family 1) Beethoven (Bth) mouse model, even though the mutant Tmc1Bth allele differs from the wild-type allele at only a single base pair. Injection of Cas9-guide RNA-lipid complexes targeting the Tmc1Bth allele into the cochlea of neonatal Tmc1Bth/+ mice substantially reduced progressive hearing loss. We observed higher hair cell survival rates and lower auditory brainstem response thresholds in injected ears than in uninjected ears or ears injected with control complexes that targeted an unrelated gene. Enhanced acoustic startle responses were observed among injected compared to uninjected Tmc1Bth/+ mice. These findings suggest that protein-RNA complex delivery of target gene-disrupting agents in vivo is a potential strategy for the treatment of some types of autosomal-dominant hearing loss.}, } @article {pmid29258296, year = {2018}, author = {Ahmadi, M and Alves, BXR and Baker, CJ and Bertsche, W and Butler, E and Capra, A and Carruth, C and Cesar, CL and Charlton, M and Cohen, S and Collister, R and Eriksson, S and Evans, A and Evetts, N and Fajans, J and Friesen, T and Fujiwara, MC and Gill, DR and Gutierrez, A and Hangst, JS and Hardy, WN and Hayden, ME and Isaac, CA and Ishida, A and Johnson, MA and Jones, SA and Jonsell, S and Kurchaninov, L and Madsen, N and Mathers, M and Maxwell, D and McKenna, JTK and Menary, S and Michan, JM and Momose, T and Munich, JJ and Nolan, P and Olchanski, K and Olin, A and Pusa, P and Rasmussen, CØ and Robicheaux, F and Sacramento, RL and Sameed, M and Sarid, E and Silveira, DM and Stracka, S and Stutter, G and So, C and Tharp, TD and Thompson, JE and Thompson, RI and van der Werf, DP and Wurtele, JS}, title = {Erratum: Observation of the hyperfine spectrum of antihydrogen.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {530}, pmid = {29258296}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23446.}, } @article {pmid29258295, year = {2018}, author = {Mack, SC and Pajtler, KW and Chavez, L and Okonechnikov, K and Bertrand, KC and Wang, X and Erkek, S and Federation, A and Song, A and Lee, C and Wang, X and McDonald, L and Morrow, JJ and Saiakhova, A and Sin-Chan, P and Wu, Q and Michaelraj, KA and Miller, TE and Hubert, CG and Ryzhova, M and Garzia, L and Donovan, L and Dombrowski, S and Factor, DC and Luu, B and Valentim, CLL and Gimple, RC and Morton, A and Kim, L and Prager, BC and Lee, JJY and Wu, X and Zuccaro, J and Thompson, Y and Holgado, BL and Reimand, J and Ke, SQ and Tropper, A and Lai, S and Vijayarajah, S and Doan, S and Mahadev, V and Miñan, AF and Gröbner, SN and Lienhard, M and Zapatka, M and Huang, Z and Aldape, KD and Carcaboso, AM and Houghton, PJ and Keir, ST and Milde, T and Witt, H and Li, Y and Li, CJ and Bian, XW and Jones, DTW and Scott, I and Singh, SK and Huang, A and Dirks, PB and Bouffet, E and Bradner, JE and Ramaswamy, V and Jabado, N and Rutka, JT and Northcott, PA and Lupien, M and Lichter, P and Korshunov, A and Scacheri, PC and Pfister, SM and Kool, M and Taylor, MD and Rich, JN}, title = {Therapeutic targeting of ependymoma as informed by oncogenic enhancer profiling.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {101-105}, pmid = {29258295}, issn = {1476-4687}, support = {R01 CA148699/CA/NCI NIH HHS/United States ; R01 CA169117/CA/NCI NIH HHS/United States ; R01 CA204279/CA/NCI NIH HHS/United States ; Z99 CA999999/NULL/Intramural NIH HHS/United States ; T32GM00725/NH/NIH HHS/United States ; R01 CA160356/CA/NCI NIH HHS/United States ; R01 CA159859/CA/NCI NIH HHS/United States ; F30 CA217065/CA/NCI NIH HHS/United States ; R01 CA171652/CA/NCI NIH HHS/United States ; R01 NS089272/NS/NINDS NIH HHS/United States ; R01 NS087913/NS/NINDS NIH HHS/United States ; R35 CA197718/CA/NCI NIH HHS/United States ; R01 CA193677/CA/NCI NIH HHS/United States ; R01 CA154130/CA/NCI NIH HHS/United States ; CA154130/NH/NIH HHS/United States ; F30 CA203101/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Base Sequence ; Enhancer Elements, Genetic/*genetics ; Ependymoma/classification/*drug therapy/*genetics/pathology ; Female ; *Gene Expression Regulation, Neoplastic ; Gene Regulatory Networks/*genetics ; Humans ; Mice ; *Molecular Targeted Therapy ; Oncogenes/*genetics ; Precision Medicine ; RNA Interference ; Transcription Factors/*metabolism ; Xenograft Model Antitumor Assays ; }, abstract = {Genomic sequencing has driven precision-based oncology therapy; however, the genetic drivers of many malignancies remain unknown or non-targetable, so alternative approaches to the identification of therapeutic leads are necessary. Ependymomas are chemotherapy-resistant brain tumours, which, despite genomic sequencing, lack effective molecular targets. Intracranial ependymomas are segregated on the basis of anatomical location (supratentorial region or posterior fossa) and further divided into distinct molecular subgroups that reflect differences in the age of onset, gender predominance and response to therapy. The most common and aggressive subgroup, posterior fossa ependymoma group A (PF-EPN-A), occurs in young children and appears to lack recurrent somatic mutations. Conversely, posterior fossa ependymoma group B (PF-EPN-B) tumours display frequent large-scale copy number gains and losses but have favourable clinical outcomes. More than 70% of supratentorial ependymomas are defined by highly recurrent gene fusions in the NF-κB subunit gene RELA (ST-EPN-RELA), and a smaller number involve fusion of the gene encoding the transcriptional activator YAP1 (ST-EPN-YAP1). Subependymomas, a distinct histologic variant, can also be found within the supratetorial and posterior fossa compartments, and account for the majority of tumours in the molecular subgroups ST-EPN-SE and PF-EPN-SE. Here we describe mapping of active chromatin landscapes in 42 primary ependymomas in two non-overlapping primary ependymoma cohorts, with the goal of identifying essential super-enhancer-associated genes on which tumour cells depend. Enhancer regions revealed putative oncogenes, molecular targets and pathways; inhibition of these targets with small molecule inhibitors or short hairpin RNA diminished the proliferation of patient-derived neurospheres and increased survival in mouse models of ependymomas. Through profiling of transcriptional enhancers, our study provides a framework for target and drug discovery in other cancers that lack known genetic drivers and are therefore difficult to treat.}, } @article {pmid29258294, year = {2018}, author = {Milanovic, M and Fan, DNY and Belenki, D and Däbritz, JHM and Zhao, Z and Yu, Y and Dörr, JR and Dimitrova, L and Lenze, D and Monteiro Barbosa, IA and Mendoza-Parra, MA and Kanashova, T and Metzner, M and Pardon, K and Reimann, M and Trumpp, A and Dörken, B and Zuber, J and Gronemeyer, H and Hummel, M and Dittmar, G and Lee, S and Schmitt, CA}, title = {Senescence-associated reprogramming promotes cancer stemness.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {96-100}, pmid = {29258294}, issn = {1476-4687}, mesh = {Animals ; Biomarkers/metabolism ; Cell Cycle Checkpoints/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; *Cellular Reprogramming/drug effects ; *Cellular Senescence/drug effects/genetics ; Clone Cells/drug effects/pathology ; Female ; Humans ; Lymphoma, B-Cell/drug therapy/genetics/*pathology ; Male ; Mice ; Mice, Transgenic ; Neoplastic Stem Cells/drug effects/*pathology ; Phenotype ; Wnt Signaling Pathway/drug effects ; }, abstract = {Cellular senescence is a stress-responsive cell-cycle arrest program that terminates the further expansion of (pre-)malignant cells. Key signalling components of the senescence machinery, such as p16INK4a, p21CIP1 and p53, as well as trimethylation of lysine 9 at histone H3 (H3K9me3), also operate as critical regulators of stem-cell functions (which are collectively termed 'stemness'). In cancer cells, a gain of stemness may have profound implications for tumour aggressiveness and clinical outcome. Here we investigated whether chemotherapy-induced senescence could change stem-cell-related properties of malignant cells. Gene expression and functional analyses comparing senescent and non-senescent B-cell lymphomas from Eμ-Myc transgenic mice revealed substantial upregulation of an adult tissue stem-cell signature, activated Wnt signalling, and distinct stem-cell markers in senescence. Using genetically switchable models of senescence targeting H3K9me3 or p53 to mimic spontaneous escape from the arrested condition, we found that cells released from senescence re-entered the cell cycle with strongly enhanced and Wnt-dependent clonogenic growth potential compared to virtually identical populations that had been equally exposed to chemotherapy but had never been senescent. In vivo, these previously senescent cells presented with a much higher tumour initiation potential. Notably, the temporary enforcement of senescence in p53-regulatable models of acute lymphoblastic leukaemia and acute myeloid leukaemia was found to reprogram non-stem bulk leukaemia cells into self-renewing, leukaemia-initiating stem cells. Our data, which are further supported by consistent results in human cancer cell lines and primary samples of human haematological malignancies, reveal that senescence-associated stemness is an unexpected, cell-autonomous feature that exerts its detrimental, highly aggressive growth potential upon escape from cell-cycle blockade, and is enriched in relapse tumours. These findings have profound implications for cancer therapy, and provide new mechanistic insights into the plasticity of cancer cells.}, } @article {pmid29258293, year = {2018}, author = {Zhang, Z and Schwanz, D and Narayanan, B and Kotiuga, M and Dura, JA and Cherukara, M and Zhou, H and Freeland, JW and Li, J and Sutarto, R and He, F and Wu, C and Zhu, J and Sun, Y and Ramadoss, K and Nonnenmann, SS and Yu, N and Comin, R and Rabe, KM and Sankaranarayanan, SKRS and Ramanathan, S}, title = {Perovskite nickelates as electric-field sensors in salt water.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {68-72}, pmid = {29258293}, issn = {1476-4687}, mesh = {Aquatic Organisms ; Calcium Compounds/*chemistry ; *Electricity ; Hydrogen-Ion Concentration ; Nickel/*chemistry ; Organometallic Compounds/*chemistry ; Oxides/*chemistry ; Phase Transition ; Protons ; Ships ; Sodium Chloride/*chemistry ; Synchrotrons ; Temperature ; Titanium/*chemistry ; Water/*chemistry ; }, abstract = {Designing materials to function in harsh environments, such as conductive aqueous media, is a problem of broad interest to a range of technologies, including energy, ocean monitoring and biological applications. The main challenge is to retain the stability and morphology of the material as it interacts dynamically with the surrounding environment. Materials that respond to mild stimuli through collective phase transitions and amplify signals could open up new avenues for sensing. Here we present the discovery of an electric-field-driven, water-mediated reversible phase change in a perovskite-structured nickelate, SmNiO3. This prototypical strongly correlated quantum material is stable in salt water, does not corrode, and allows exchange of protons with the surrounding water at ambient temperature, with the concurrent modification in electrical resistance and optical properties being capable of multi-modal readout. Besides operating both as thermistors and pH sensors, devices made of this material can detect sub-volt electric potentials in salt water. We postulate that such devices could be used in oceanic environments for monitoring electrical signals from various maritime vessels and sea creatures.}, } @article {pmid29258292, year = {2018}, author = {Abbosh, C and Birkbak, NJ and Wilson, GA and Jamal-Hanjani, M and Constantin, T and Salari, R and Le Quesne, J and Moore, DA and Veeriah, S and Rosenthal, R and Marafioti, T and Kirkizlar, E and Watkins, TBK and McGranahan, N and Ward, S and Martinson, L and Riley, J and Fraioli, F and Al Bakir, M and Grönroos, E and Zambrana, F and Endozo, R and Bi, WL and Fennessy, FM and Sponer, N and Johnson, D and Laycock, J and Shafi, S and Czyzewska-Khan, J and Rowan, A and Chambers, T and Matthews, N and Turajlic, S and Hiley, C and Lee, SM and Forster, MD and Ahmad, T and Falzon, M and Borg, E and Lawrence, D and Hayward, M and Kolvekar, S and Panagiotopoulos, N and Janes, SM and Thakrar, R and Ahmed, A and Blackhall, F and Summers, Y and Hafez, D and Naik, A and Ganguly, A and Kareht, S and Shah, R and Joseph, L and Quinn, AM and Crosbie, PA and Naidu, B and Middleton, G and Langman, G and Trotter, S and Nicolson, M and Remmen, H and Kerr, K and Chetty, M and Gomersall, L and Fennell, DA and Nakas, A and Rathinam, S and Anand, G and Khan, S and Russell, P and Ezhil, V and Ismail, B and Irvin-Sellers, M and Prakash, V and Lester, JF and Kornaszewska, M and Attanoos, R and Adams, H and Davies, H and Oukrif, D and Akarca, AU and Hartley, JA and Lowe, HL and Lock, S and Iles, N and Bell, H and Ngai, Y and Elgar, G and Szallasi, Z and Schwarz, RF and Herrero, J and Stewart, A and Quezada, SA and Peggs, KS and Van Loo, P and Dive, C and Lin, CJ and Rabinowitz, M and Aerts, HJWL and Hackshaw, A and Shaw, JA and Zimmermann, BG and Swanton, C}, title = {Corrigendum: Phylogenetic ctDNA analysis depicts early-stage lung cancer evolution.}, journal = {Nature}, volume = {554}, number = {7691}, pages = {264}, pmid = {29258292}, issn = {1476-4687}, support = {G108/596//Medical Research Council/United Kingdom ; MC_UP_1203/1//Medical Research Council/United Kingdom ; }, abstract = {This corrects the article DOI: 10.1038/nature22364.}, } @article {pmid29258291, year = {2018}, author = {Amano, T and Székely, T and Sandel, B and Nagy, S and Mundkur, T and Langendoen, T and Blanco, D and Soykan, CU and Sutherland, WJ}, title = {Successful conservation of global waterbird populations depends on effective governance.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {199-202}, pmid = {29258291}, issn = {1476-4687}, mesh = {Africa ; Animals ; Asia ; *Biodiversity ; *Birds/classification ; Conservation of Natural Resources/*legislation & jurisprudence ; Geographic Mapping ; *International Cooperation ; Population Density ; South America ; Species Specificity ; *Wetlands ; }, abstract = {Understanding global patterns of biodiversity change is crucial for conservation research, policies and practices. However, for most ecosystems, the lack of systematically collected data at a global level limits our understanding of biodiversity changes and their local-scale drivers. Here we address this challenge by focusing on wetlands, which are among the most biodiverse and productive of any environments and which provide essential ecosystem services, but are also amongst the most seriously threatened ecosystems. Using birds as an indicator taxon of wetland biodiversity, we model time-series abundance data for 461 waterbird species at 25,769 survey sites across the globe. We show that the strongest predictor of changes in waterbird abundance, and of conservation efforts having beneficial effects, is the effective governance of a country. In areas in which governance is on average less effective, such as western and central Asia, sub-Saharan Africa and South America, waterbird declines are particularly pronounced; a higher protected area coverage of wetland environments facilitates waterbird increases, but only in countries with more effective governance. Our findings highlight that sociopolitical instability can lead to biodiversity loss and undermine the benefit of existing conservation efforts, such as the expansion of protected area coverage. Furthermore, data deficiencies in areas with less effective governance could lead to underestimations of the extent of the current biodiversity crisis.}, } @article {pmid29258290, year = {2018}, author = {, }, title = {Erratum: Genetic effects on gene expression across human tissues.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {530}, pmid = {29258290}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24277.}, } @article {pmid29258289, year = {2018}, author = {McGoldrick, LL and Singh, AK and Saotome, K and Yelshanskaya, MV and Twomey, EC and Grassucci, RA and Sobolevsky, AI}, title = {Opening of the human epithelial calcium channel TRPV6.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {233-237}, pmid = {29258289}, issn = {1476-4687}, support = {F31 NS093838/NS/NINDS NIH HHS/United States ; P41 GM103310/GM/NIGMS NIH HHS/United States ; R01 NS083660/NS/NINDS NIH HHS/United States ; T32 GM008224/GM/NIGMS NIH HHS/United States ; R01 CA206573/CA/NCI NIH HHS/United States ; }, mesh = {Alanine/metabolism ; Calcium/metabolism ; Calcium Channels/chemistry/*metabolism/*ultrastructure ; *Cryoelectron Microscopy ; Epithelial Cells/*metabolism ; Humans ; *Ion Channel Gating ; Ion Transport ; Protein Conformation ; Rotation ; TRPV Cation Channels/chemistry/*metabolism/*ultrastructure ; }, abstract = {Calcium-selective transient receptor potential vanilloid subfamily member 6 (TRPV6) channels play a critical role in calcium uptake in epithelial tissues. Altered TRPV6 expression is associated with a variety of human diseases, including cancers. TRPV6 channels are constitutively active and their open probability depends on the lipidic composition of the membrane in which they reside; it increases substantially in the presence of phosphatidylinositol 4,5-bisphosphate. Crystal structures of detergent-solubilized rat TRPV6 in the closed state have previously been solved. Corroborating electrophysiological results, these structures demonstrated that the Ca2+ selectivity of TRPV6 arises from a ring of aspartate side chains in the selectivity filter that binds Ca2+ tightly. However, how TRPV6 channels open and close their pores for ion permeation has remained unclear. Here we present cryo-electron microscopy structures of human TRPV6 in the open and closed states. The channel selectivity filter adopts similar conformations in both states, consistent with its explicit role in ion permeation. The iris-like channel opening is accompanied by an α-to-π-helical transition in the pore-lining transmembrane helix S6 at an alanine hinge just below the selectivity filter. As a result of this transition, the S6 helices bend and rotate, exposing different residues to the ion channel pore in the open and closed states. This gating mechanism, which defines the constitutive activity of TRPV6, is, to our knowledge, unique among tetrameric ion channels and provides structural insights for understanding their diverse roles in physiology and disease.}, } @article {pmid29258288, year = {2018}, author = {Erb, KH and Kastner, T and Plutzar, C and Bais, ALS and Carvalhais, N and Fetzel, T and Gingrich, S and Haberl, H and Lauk, C and Niedertscheider, M and Pongratz, J and Thurner, M and Luyssaert, S}, title = {Unexpectedly large impact of forest management and grazing on global vegetation biomass.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {73-76}, pmid = {29258288}, issn = {1476-4687}, support = {263522//European Research Council/International ; }, mesh = {*Animal Husbandry ; Animals ; *Biomass ; Carbon/analysis ; Carbon Sequestration ; Conservation of Natural Resources/legislation & jurisprudence ; *Forestry ; *Forests ; Global Warming/legislation & jurisprudence/prevention & control ; *Human Activities ; *Internationality ; Plants/chemistry/*metabolism ; Trees/chemistry/metabolism ; Tropical Climate ; Uncertainty ; }, abstract = {Carbon stocks in vegetation have a key role in the climate system. However, the magnitude, patterns and uncertainties of carbon stocks and the effect of land use on the stocks remain poorly quantified. Here we show, using state-of-the-art datasets, that vegetation currently stores around 450 petagrams of carbon. In the hypothetical absence of land use, potential vegetation would store around 916 petagrams of carbon, under current climate conditions. This difference highlights the massive effect of land use on biomass stocks. Deforestation and other land-cover changes are responsible for 53-58% of the difference between current and potential biomass stocks. Land management effects (the biomass stock changes induced by land use within the same land cover) contribute 42-47%, but have been underestimated in the literature. Therefore, avoiding deforestation is necessary but not sufficient for mitigation of climate change. Our results imply that trade-offs exist between conserving carbon stocks on managed land and raising the contribution of biomass to raw material and energy supply for the mitigation of climate change. Efforts to raise biomass stocks are currently verifiable only in temperate forests, where their potential is limited. By contrast, large uncertainties hinder verification in the tropical forest, where the largest potential is located, pointing to challenges for the upcoming stocktaking exercises under the Paris agreement.}, } @article {pmid29258058, year = {2018}, author = {Carlson-Banning, KM and Sperandio, V}, title = {Enterohemorrhagic Escherichia coli outwits hosts through sensing small molecules.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {83-88}, pmid = {29258058}, issn = {1879-0364}, support = {R01 AI114511/AI/NIAID NIH HHS/United States ; R01 AI077613/AI/NIAID NIH HHS/United States ; T32 AI007520/AI/NIAID NIH HHS/United States ; R01 AI105135/AI/NIAID NIH HHS/United States ; R01 AI053067/AI/NIAID NIH HHS/United States ; R37 AI053067/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Enterohemorrhagic Escherichia coli/*genetics/*metabolism/pathogenicity ; Epinephrine/metabolism ; Escherichia coli Infections/microbiology ; Escherichia coli Proteins/genetics/metabolism ; Ethanolamine/metabolism ; Gastrointestinal Tract/*microbiology ; Gene Expression Regulation, Bacterial ; *Host-Pathogen Interactions/physiology ; Humans ; Mice ; Microbiota/physiology ; Mucins/metabolism ; Oxygen/metabolism ; Type III Secretion Systems/genetics/metabolism ; Virulence ; Virulence Factors ; }, abstract = {Small molecules help intestinal pathogens navigate the complex human gastrointestinal tract to exploit favorable microhabitats. These small molecules provide spatial landmarks for pathogens to regulate synthesis of virulence caches and are derived from the host, ingested plant and animal material, and the microbiota. Their concentrations and fluxes vary along the length of the gut and provide molecular signatures that are beginning to be explored through metabolomics and genetics. However, while many small molecules have been identified and are reviewed here, there are undoubtedly others that may also profoundly affect how enteric pathogens infect their hosts.}, } @article {pmid29256852, year = {2018}, author = {Divyasree, B and Suresh, G and Sasikala, C and Ramana, CV}, title = {Chryseobacterium salipaludis sp. nov., isolated at a wild ass sanctuary.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {542-546}, doi = {10.1099/ijsem.0.002536}, pmid = {29256852}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Chryseobacterium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; *Equidae ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; India ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, rod-shaped, non-motile, aerobic bacterium was isolated from a sediment sample obtained from a wild ass sanctuary in Gujarat, India. The strain designated JC490T was oxidase- and catalase-positive. The 16S rRNA gene sequence analysis and sequence comparison data indicated that strain JC490T was a member of the genus Chryseobacterium and was closely related to Chryseobacterium jeonii AT1047T (96.4 %) and with other members of the genus Chryseobacterium (<96.3 %). The DNA G+C content of strain JC490T was 34 mol%. Strain JC490T had phosphatidylethanolamine, two unidentified aminolipids, two unidentified phospholipids and five unidentified polar lipids. Menaquinone-6 was the only respiratory quinone found. Iso-C15 : 0, anteiso-C15 : 0 and iso-C17 : 0 3-OH were the major fatty acids of strain JC490T. On the basis of physiological, genotypic, phylogenetic and chemotaxonomic analyses, it is concluded that strain JC490T constitutes a novel species of the genus Chryseobacterium, for which the name Chryseobacterium salipaludis sp. nov. is proposed. The type strain is JC490T (=KCTC 52835T=LMG 30048T).}, } @article {pmid29256008, year = {2018}, author = {Híreš, M and Rapavá, N and Šimkovič, M and Varečka, Ľ and Berkeš, D and Kryštofová, S}, title = {Development and Optimization of a High-Throughput Screening Assay for Rapid Evaluation of Lipstatin Production by Streptomyces Strains.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {580-587}, pmid = {29256008}, issn = {1432-0991}, support = {26220220093//ITMS/ ; APVV-0719-12//Grant of Science and Technology Assistance Agency/ ; 047STU-4/2016//KEGA/ ; }, mesh = {Culture Media/metabolism ; Enzyme Inhibitors/*chemistry/metabolism ; High-Throughput Screening Assays/*methods ; Lactones/*chemistry/metabolism ; Lipase/antagonists & inhibitors/chemistry ; Streptomyces/*chemistry/metabolism ; }, abstract = {Pancreatic lipase inhibitors, such as tetrahydrolipstatin (orlistat), are used in anti-obesity treatments. Orlistat is the only anti-obesity drug approved by the European Medicines Agency (EMA). The drug is synthesized by saturation of lipstatin, a β-lactone compound, isolated from Streptomyces toxytricini and S. virginiae. To identify producers of novel pancreatic lipase inhibitors or microbial strains with improved lipstatin production and higher chemical purity remains still a priority. In this study, a high-throughput screening method to identify Streptomyces strains producing potent pancreatic lipase inhibitors was established. The assay was optimized and validated using S. toxytricini NRRL 15443 and its mutants. Strains grew in 24-well titer plates. Lipstatin levels were assessed directly in culture medium at the end of cultivation by monitoring lipolytic activity in the presence of a chromogenic substrate, 1,2-Di-O-lauryl-rac-glycero-3-glutaric acid 6-methylresorufin ester (DGGR). The lipase activity decreased in response to lipstatin production, and this was demonstrated by accumulation of red-purple methylresorufin, a product of DGGR digestion. The sensitivity of the assay was achieved by adding a lipase of high lipolytic activity and sensitivity to lipstatin to the reaction mixture. In the assay, the fungal lipase from Mucor javanicus was used as an alternative to the human pancreatic lipase. Many fungal lipases preserve high lipolytic activity in extreme conditions and are not colipase dependent. The assay proved to be reliable in differentiation of strains with high and low lipstatin productivity.}, } @article {pmid29255304, year = {2018}, author = {Rono, MK and Nyonda, MA and Simam, JJ and Ngoi, JM and Mok, S and Kortok, MM and Abdullah, AS and Elfaki, MM and Waitumbi, JN and El-Hassan, IM and Marsh, K and Bozdech, Z and Mackinnon, MJ}, title = {Adaptation of Plasmodium falciparum to its transmission environment.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {377-387}, doi = {10.1038/s41559-017-0419-9}, pmid = {29255304}, issn = {2397-334X}, abstract = {Success in eliminating malaria will depend on whether parasite evolution outpaces control efforts. Here, we show that Plasmodium falciparum parasites (the deadliest of the species causing human malaria) found in low-transmission-intensity areas have evolved to invest more in transmission to new hosts (reproduction) and less in within-host replication (growth) than parasites found in high-transmission areas. At the cellular level, this adaptation manifests as increased production of reproductive forms (gametocytes) early in the infection at the expense of processes associated with multiplication inside red blood cells, especially membrane transport and protein trafficking. At the molecular level, this manifests as changes in the expression levels of genes encoding epigenetic and translational machinery. Specifically, expression levels of the gene encoding AP2-G-the transcription factor that initiates reproduction-increase as transmission intensity decreases. This is accompanied by downregulation and upregulation of genes encoding HDAC1 and HDA1-two histone deacetylases that epigenetically regulate the parasite's replicative and reproductive life-stage programmes, respectively. Parasites in reproductive mode show increased reliance on the prokaryotic translation machinery found inside the plastid-derived organelles. Thus, our dissection of the parasite's adaptive regulatory architecture has identified new potential molecular targets for malaria control.}, } @article {pmid29255303, year = {2018}, author = {Exposito-Alonso, M and Vasseur, F and Ding, W and Wang, G and Burbano, HA and Weigel, D}, title = {Genomic basis and evolutionary potential for extreme drought adaptation in Arabidopsis thaliana.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {352-358}, pmid = {29255303}, issn = {2397-334X}, support = {340602//European Research Council/International ; }, abstract = {As Earth is currently experiencing dramatic climate change, it is of critical interest to understand how species will respond to it. The chance of a species withstanding climate change is likely to depend on the diversity within the species and, particularly, whether there are sub-populations that are already adapted to extreme environments. However, most predictive studies ignore that species comprise genetically diverse individuals. We have identified genetic variants in Arabidopsis thaliana that are associated with survival of an extreme drought event-a major consequence of global warming. Subsequently, we determined how these variants are distributed across the native range of the species. Genetic alleles conferring higher drought survival showed signatures of polygenic adaptation and were more frequently found in Mediterranean and Scandinavian regions. Using geo-environmental models, we predicted that Central European, but not Mediterranean, populations might lag behind in adaptation by the end of the twenty-first century. Further analyses showed that a population decline could nevertheless be compensated by natural selection acting efficiently over standing variation or by migration of adapted individuals from populations at the margins of the species' distribution. These findings highlight the importance of within-species genetic heterogeneity in facilitating an evolutionary response to a changing climate.}, } @article {pmid29255302, year = {2018}, author = {Thorogood, R and Kokko, H and Mappes, J}, title = {Social transmission of avoidance among predators facilitates the spread of novel prey.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {254-261}, doi = {10.1038/s41559-017-0418-x}, pmid = {29255302}, issn = {2397-334X}, abstract = {Warning signals are an effective defence strategy for aposematic prey, but only if they are recognized by potential predators. If predators must eat prey to associate novel warning signals with unpalatability, how can aposematic prey ever evolve? Using experiments with great tits (Parus major) as predators, we show that social transmission enhances the acquisition of avoidance by a predator population. Observing another predator's disgust towards tasting one novel conspicuous prey item led to fewer aposematic than cryptic prey being eaten for the predator population to learn. Despite reduced personal encounters with unpalatable prey, avoidance persisted and increased over subsequent trials. Next we use a mathematical model to show that social transmission can shift the evolutionary trajectory of prey populations from fixation of crypsis to fixation of aposematism more easily than was previously thought. Therefore, social information use by predators has the potential to have evolutionary consequences across ecological communities.}, } @article {pmid29255301, year = {2018}, author = {Brown, LE and Khamis, K and Wilkes, M and Blaen, P and Brittain, JE and Carrivick, JL and Fell, S and Friberg, N and Füreder, L and Gislason, GM and Hainie, S and Hannah, DM and James, WHM and Lencioni, V and Olafsson, JS and Robinson, CT and Saltveit, SJ and Thompson, C and Milner, AM}, title = {Functional diversity and community assembly of river invertebrates show globally consistent responses to decreasing glacier cover.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {325-333}, doi = {10.1038/s41559-017-0426-x}, pmid = {29255301}, issn = {2397-334X}, abstract = {Global change threatens invertebrate biodiversity and its central role in numerous ecosystem functions and services. Functional trait analyses have been advocated to uncover global mechanisms behind biodiversity responses to environmental change, but the application of this approach for invertebrates is underdeveloped relative to other organism groups. From an evaluation of 363 records comprising >1.23 million invertebrates collected from rivers across nine biogeographic regions on three continents, consistent responses of community trait composition and diversity to replicated gradients of reduced glacier cover are demonstrated. After accounting for a systematic regional effect of latitude, the processes shaping river invertebrate functional diversity are globally consistent. Analyses nested within individual regions identified an increase in functional diversity as glacier cover decreases. Community assembly models demonstrated that dispersal limitation was the dominant process underlying these patterns, although environmental filtering was also evident in highly glacierized basins. These findings indicate that predictable mechanisms govern river invertebrate community responses to decreasing glacier cover globally.}, } @article {pmid29255300, year = {2018}, author = {Esin, A and Bergendahl, LT and Savolainen, V and Marsh, JA and Warnecke, T}, title = {The genetic basis and evolution of red blood cell sickling in deer.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {367-376}, pmid = {29255300}, issn = {2397-334X}, support = {MC_UP_1102/7//Medical Research Council/United Kingdom ; MR/M02122X/1//Medical Research Council/United Kingdom ; }, abstract = {Crescent-shaped red blood cells, the hallmark of sickle-cell disease, present a striking departure from the biconcave disc shape normally found in mammals. Characterized by increased mechanical fragility, sickled cells promote haemolytic anaemia and vaso-occlusions and contribute directly to disease in humans. Remarkably, a similar sickle-shaped morphology has been observed in erythrocytes from several deer species, without obvious pathological consequences. The genetic basis of erythrocyte sickling in deer, however, remains unknown. Here, we determine the sequences of human β-globin orthologues in 15 deer species and use protein structural modelling to identify a sickling mechanism distinct from the human disease, coordinated by a derived valine (E22V) that is unique to sickling deer. Evidence for long-term maintenance of a trans-species sickling/non-sickling polymorphism suggests that sickling in deer is adaptive. Our results have implications for understanding the ecological regimes and molecular architectures that have promoted convergent evolution of sickling erythrocytes across vertebrates.}, } @article {pmid29255299, year = {2018}, author = {Fanin, N and Gundale, MJ and Farrell, M and Ciobanu, M and Baldock, JA and Nilsson, MC and Kardol, P and Wardle, DA}, title = {Consistent effects of biodiversity loss on multifunctionality across contrasting ecosystems.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {269-278}, doi = {10.1038/s41559-017-0415-0}, pmid = {29255299}, issn = {2397-334X}, abstract = {Understanding how loss of biodiversity affects ecosystem functioning, and thus the delivery of ecosystem goods and services, has become increasingly necessary in a changing world. Considerable recent attention has focused on predicting how biodiversity loss simultaneously impacts multiple ecosystem functions (that is, ecosystem multifunctionality), but the ways in which these effects vary across ecosystems remain unclear. Here, we report the results of two 19-year plant diversity manipulation experiments, each established across a strong environmental gradient. Although the effects of plant and associated fungal diversity loss on individual functions frequently differed among ecosystems, the consequences of biodiversity loss for multifunctionality were relatively invariant. However, the context-dependency of biodiversity effects also worked in opposing directions for different individual functions, meaning that similar multifunctionality values across contrasting ecosystems could potentially mask important differences in the effects of biodiversity on functioning among ecosystems. Our findings highlight that an understanding of the relative contribution of species or functional groups to individual ecosystem functions among contrasting ecosystems and their interactions (that is, complementarity versus competition) is critical for guiding management efforts aimed at maintaining ecosystem multifunctionality and the delivery of multiple ecosystem services.}, } @article {pmid29255298, year = {2018}, author = {Schunter, C and Welch, MJ and Nilsson, GE and Rummer, JL and Munday, PL and Ravasi, T}, title = {An interplay between plasticity and parental phenotype determines impacts of ocean acidification on a reef fish.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {334-342}, doi = {10.1038/s41559-017-0428-8}, pmid = {29255298}, issn = {2397-334X}, abstract = {The impacts of ocean acidification will depend on the ability of marine organisms to tolerate, acclimate and eventually adapt to changes in ocean chemistry. Here, we use a unique transgenerational experiment to determine the molecular response of a coral reef fish to short-term, developmental and transgenerational exposure to elevated CO2, and to test how these responses are influenced by variations in tolerance to elevated CO2 exhibited by the parents. Within-generation responses in gene expression to end-of-century predicted CO2 levels indicate that a self-amplifying cycle in GABAergic neurotransmission is triggered, explaining previously reported neurological and behavioural impairments. Furthermore, epigenetic regulator genes exhibited a within-generation specific response, but with some divergence due to parental phenotype. Importantly, we find that altered gene expression for the majority of within-generation responses returns to baseline levels following parental exposure to elevated CO2 conditions. Our results show that both parental variation in tolerance and cross-generation exposure to elevated CO2 are crucial factors in determining the response of reef fish to changing ocean chemistry.}, } @article {pmid29255297, year = {2018}, author = {Kimmerling, N and Zuqert, O and Amitai, G and Gurevich, T and Armoza-Zvuloni, R and Kolesnikov, I and Berenshtein, I and Melamed, S and Gilad, S and Benjamin, S and Rivlin, A and Ohavia, M and Paris, CB and Holzman, R and Kiflawi, M and Sorek, R}, title = {Quantitative species-level ecology of reef fish larvae via metabarcoding.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {306-316}, doi = {10.1038/s41559-017-0413-2}, pmid = {29255297}, issn = {2397-334X}, abstract = {The larval pool of coral reef fish has a crucial role in the dynamics of adult fish populations. However, large-scale species-level monitoring of species-rich larval pools has been technically impractical. Here, we use high-throughput metabarcoding to study larval ecology in the Gulf of Aqaba, a region that is inhabited by >500 reef fish species. We analysed 9,933 larvae from 383 samples that were stratified over sites, depth and time. Metagenomic DNA extracted from pooled larvae was matched to a mitochondrial cytochrome c oxidase subunit I barcode database compiled for 77% of known fish species within this region. This yielded species-level reconstruction of the larval community, allowing robust estimation of larval spatio-temporal distributions. We found significant correlations between species abundance in the larval pool and in local adult assemblages, suggesting a major role for larval supply in determining local adult densities. We documented larval flux of species whose adults were never documented in the region, suggesting environmental filtering as the reason for the absence of these species. Larvae of several deep-sea fishes were found in shallow waters, supporting their dispersal over shallow bathymetries, potentially allowing Lessepsian migration into the Mediterranean Sea. Our method is applicable to any larval community and could assist coral reef conservation and fishery management efforts.}, } @article {pmid29255284, year = {2018}, author = {Costea, PI and Hildebrand, F and Arumugam, M and Bäckhed, F and Blaser, MJ and Bushman, FD and de Vos, WM and Ehrlich, SD and Fraser, CM and Hattori, M and Huttenhower, C and Jeffery, IB and Knights, D and Lewis, JD and Ley, RE and Ochman, H and O'Toole, PW and Quince, C and Relman, DA and Shanahan, F and Sunagawa, S and Wang, J and Weinstock, GM and Wu, GD and Zeller, G and Zhao, L and Raes, J and Knight, R and Bork, P}, title = {Enterotypes in the landscape of gut microbial community composition.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {8-16}, pmid = {29255284}, issn = {2058-5276}, support = {MR/M50161X/1//Medical Research Council/United Kingdom ; P30 AI045008/AI/NIAID NIH HHS/United States ; P30 DK050306/DK/NIDDK NIH HHS/United States ; UH2 DK083981/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Bacteria/*classification/genetics ; Bacterial Typing Techniques ; Biodiversity ; Gastrointestinal Microbiome/*genetics ; Gastrointestinal Tract/*microbiology ; Humans ; *Metagenome ; Metagenomics ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Population stratification is a useful approach for a better understanding of complex biological problems in human health and wellbeing. The proposal that such stratification applies to the human gut microbiome, in the form of distinct community composition types termed enterotypes, has been met with both excitement and controversy. In view of accumulated data and re-analyses since the original work, we revisit the concept of enterotypes, discuss different methods of dividing up the landscape of possible microbiome configurations, and put these concepts into functional, ecological and medical contexts. As enterotypes are of use in describing the gut microbial community landscape and may become relevant in clinical practice, we aim to reconcile differing views and encourage a balanced application of the concept.}, } @article {pmid29255283, year = {2018}, author = {Stappenbeck, TS}, title = {Assigning function to symbionts.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {6-7}, doi = {10.1038/s41564-017-0088-0}, pmid = {29255283}, issn = {2058-5276}, } @article {pmid29255282, year = {2018}, author = {Dambuza, IM and Brown, GD}, title = {Sensing fungi at the oral epithelium.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {4-5}, doi = {10.1038/s41564-017-0086-2}, pmid = {29255282}, issn = {2058-5276}, } @article {pmid29255281, year = {2018}, author = {Price, JE and Chapman, MR}, title = {Phaged and confused by biofilm matrix.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {2-3}, doi = {10.1038/s41564-017-0078-2}, pmid = {29255281}, issn = {2058-5276}, support = {R01 GM118651/GM/NIGMS NIH HHS/United States ; }, } @article {pmid29255280, year = {2018}, author = {}, title = {Peer review is not broken.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {1}, doi = {10.1038/s41564-017-0093-3}, pmid = {29255280}, issn = {2058-5276}, } @article {pmid29255266, year = {2018}, author = {Verma, N and Pan, H and Doré, LC and Shukla, A and Li, QV and Pelham-Webb, B and Teijeiro, V and González, F and Krivtsov, A and Chang, CJ and Papapetrou, EP and He, C and Elemento, O and Huangfu, D}, title = {Publisher Correction: TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {764}, doi = {10.1038/s41588-017-0024-5}, pmid = {29255266}, issn = {1546-1718}, abstract = {The version of the Supplementary Text and Figures file initially posted was missing Supplementary Tables 1-6 and the Supplementary Note and used incorrect versions of the supplementary figures.}, } @article {pmid29255265, year = {2018}, author = {Verma, N and Pan, H and Doré, LC and Shukla, A and Li, QV and Pelham-Webb, B and Teijeiro, V and González, F and Krivtsov, A and Chang, CJ and Papapetrou, EP and He, C and Elemento, O and Huangfu, D}, title = {Author Correction: TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells.}, journal = {Nature genetics}, volume = {50}, number = {5}, pages = {764}, doi = {10.1038/s41588-017-0025-4}, pmid = {29255265}, issn = {1546-1718}, abstract = {In the version of this article initially published, in the Methods, the Gene Expression Omnibus accession code for H3K36me3 ChIP-seq data was incorrectly given as GSM1003585 instead of GSM733725. The error has been corrected in the HTML, PDF and print versions of the article.}, } @article {pmid29255264, year = {2018}, author = {Local, A and Huang, H and Albuquerque, CP and Singh, N and Lee, AY and Wang, W and Wang, C and Hsia, JE and Shiau, AK and Ge, K and Corbett, KD and Wang, D and Zhou, H and Ren, B}, title = {Identification of H3K4me1-associated proteins at mammalian enhancers.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {73-82}, pmid = {29255264}, issn = {1546-1718}, support = {R01 GM102362/GM/NIGMS NIH HHS/United States ; R01 GM115961/GM/NIGMS NIH HHS/United States ; R01 GM116897/GM/NIGMS NIH HHS/United States ; T32 CA009523/CA/NCI NIH HHS/United States ; }, abstract = {Enhancers act to regulate cell-type-specific gene expression by facilitating the transcription of target genes. In mammalian cells, active or primed enhancers are commonly marked by monomethylation of histone H3 at lysine 4 (H3K4me1) in a cell-type-specific manner. Whether and how this histone modification regulates enhancer-dependent transcription programs in mammals is unclear. In this study, we conducted SILAC mass spectrometry experiments with mononucleosomes and identified multiple H3K4me1-associated proteins, including many involved in chromatin remodeling. We demonstrate that H3K4me1 augments association of the chromatin-remodeling complex BAF to enhancers in vivo and that, in vitro, H3K4me1-marked nucleosomes are more efficiently remodeled by the BAF complex. Crystal structures of the BAF component BAF45C indicate that monomethylation, but not trimethylation, is accommodated by BAF45C's H3K4-binding site. Our results suggest that H3K4me1 has an active role at enhancers by facilitating binding of the BAF complex and possibly other chromatin regulators.}, } @article {pmid29255263, year = {2018}, author = {Rodriguez-Terrones, D and Gaume, X and Ishiuchi, T and Weiss, A and Kopp, A and Kruse, K and Penning, A and Vaquerizas, JM and Brino, L and Torres-Padilla, ME}, title = {A molecular roadmap for the emergence of early-embryonic-like cells in culture.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {106-119}, pmid = {29255263}, issn = {1546-1718}, support = {280840//European Research Council/International ; }, abstract = {Unlike pluripotent cells, which generate only embryonic tissues, totipotent cells can generate a full organism, including extra-embryonic tissues. A rare population of cells resembling 2-cell-stage embryos arises in pluripotent embryonic stem (ES) cell cultures. These 2-cell-like cells display molecular features of totipotency and broader developmental plasticity. However, their specific nature and the process through which they arise remain outstanding questions. Here we identified intermediate cellular states and molecular determinants during the emergence of 2-cell-like cells. By deploying a quantitative single-cell expression approach, we identified an intermediate population characterized by expression of the transcription factor ZSCAN4 as a precursor of 2-cell-like cells. By using a small interfering RNA (siRNA) screen, we identified epigenetic regulators of 2-cell-like cell emergence, including the non-canonical PRC1 complex PRC1.6 and the EP400-TIP60 complex. Our data shed light on the mechanisms that underlie exit from the ES cell state toward the formation of early-embryonic-like cells in culture and identify key epigenetic pathways that promote this transition.}, } @article {pmid29255262, year = {2018}, author = {Pol, A and Renkema, GH and Tangerman, A and Winkel, EG and Engelke, UF and de Brouwer, APM and Lloyd, KC and Araiza, RS and van den Heuvel, L and Omran, H and Olbrich, H and Oude Elberink, M and Gilissen, C and Rodenburg, RJ and Sass, JO and Schwab, KO and Schäfer, H and Venselaar, H and Sequeira, JS and Op den Camp, HJM and Wevers, RA}, title = {Mutations in SELENBP1, encoding a novel human methanethiol oxidase, cause extraoral halitosis.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {120-129}, pmid = {29255262}, issn = {1546-1718}, support = {BB/H003851/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; P30 CA093373/CA/NCI NIH HHS/United States ; UM1 OD023221/OD/NIH HHS/United States ; U42 OD012210/OD/NIH HHS/United States ; 669371//European Research Council/International ; }, abstract = {Selenium-binding protein 1 (SELENBP1) has been associated with several cancers, although its exact role is unknown. We show that SELENBP1 is a methanethiol oxidase (MTO), related to the MTO in methylotrophic bacteria, that converts methanethiol to H2O2, formaldehyde, and H2S, an activity not previously known to exist in humans. We identified mutations in SELENBP1 in five patients with cabbage-like breath odor. The malodor was attributable to high levels of methanethiol and dimethylsulfide, the main odorous compounds in their breath. Elevated urinary excretion of dimethylsulfoxide was associated with MTO deficiency. Patient fibroblasts had low SELENBP1 protein levels and were deficient in MTO enzymatic activity; these effects were reversed by lentivirus-mediated expression of wild-type SELENBP1. Selenbp1-knockout mice showed biochemical characteristics similar to those in humans. Our data reveal a potentially frequent inborn error of metabolism that results from MTO deficiency and leads to a malodor syndrome.}, } @article {pmid29255261, year = {2018}, author = {Luciano, M and Hagenaars, SP and Davies, G and Hill, WD and Clarke, TK and Shirali, M and Harris, SE and Marioni, RE and Liewald, DC and Fawns-Ritchie, C and Adams, MJ and Howard, DM and Lewis, CM and Gale, CR and McIntosh, AM and Deary, IJ}, title = {Association analysis in over 329,000 individuals identifies 116 independent variants influencing neuroticism.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {6-11}, pmid = {29255261}, issn = {1546-1718}, support = {MC_UP_A620_1015//Medical Research Council/United Kingdom ; MC_QA137853//Medical Research Council/United Kingdom ; MC_UU_12011/2//Medical Research Council/United Kingdom ; MC_U147585819//Medical Research Council/United Kingdom ; MR/K026992/1//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; }, abstract = {Neuroticism is a relatively stable personality trait characterized by negative emotionality (for example, worry and guilt) 1 ; heritability estimated from twin studies ranges from 30 to 50% 2 , and SNP-based heritability ranges from 6 to 15% 3-6 . Increased neuroticism is associated with poorer mental and physical health 7,8 , translating to high economic burden 9 . Genome-wide association studies (GWAS) of neuroticism have identified up to 11 associated genetic loci 3,4 . Here we report 116 significant independent loci from a GWAS of neuroticism in 329,821 UK Biobank participants; 15 of these loci replicated at P < 0.00045 in an unrelated cohort (N = 122,867). Genetic signals were enriched in neuronal genesis and differentiation pathways, and substantial genetic correlations were found between neuroticism and depressive symptoms (r g = 0.82, standard error (s.e.) = 0.03), major depressive disorder (MDD; r g = 0.69, s.e. = 0.07) and subjective well-being (r g = -0.68, s.e. = 0.03) alongside other mental health traits. These discoveries significantly advance understanding of neuroticism and its association with MDD.}, } @article {pmid29255260, year = {2018}, author = {Levy, A and Salas Gonzalez, I and Mittelviefhaus, M and Clingenpeel, S and Herrera Paredes, S and Miao, J and Wang, K and Devescovi, G and Stillman, K and Monteiro, F and Rangel Alvarez, B and Lundberg, DS and Lu, TY and Lebeis, S and Jin, Z and McDonald, M and Klein, AP and Feltcher, ME and Rio, TG and Grant, SR and Doty, SL and Ley, RE and Zhao, B and Venturi, V and Pelletier, DA and Vorholt, JA and Tringe, SG and Woyke, T and Dangl, JL}, title = {Genomic features of bacterial adaptation to plants.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {138-150}, pmid = {29255260}, issn = {1546-1718}, support = {//Howard Hughes Medical Institute/United States ; F32 GM112345/GM/NIGMS NIH HHS/United States ; T32 GM007092/GM/NIGMS NIH HHS/United States ; T32 GM067553/GM/NIGMS NIH HHS/United States ; }, abstract = {Plants intimately associate with diverse bacteria. Plant-associated bacteria have ostensibly evolved genes that enable them to adapt to plant environments. However, the identities of such genes are mostly unknown, and their functions are poorly characterized. We sequenced 484 genomes of bacterial isolates from roots of Brassicaceae, poplar, and maize. We then compared 3,837 bacterial genomes to identify thousands of plant-associated gene clusters. Genomes of plant-associated bacteria encode more carbohydrate metabolism functions and fewer mobile elements than related non-plant-associated genomes do. We experimentally validated candidates from two sets of plant-associated genes: one involved in plant colonization, and the other serving in microbe-microbe competition between plant-associated bacteria. We also identified 64 plant-associated protein domains that potentially mimic plant domains; some are shared with plant-associated fungi and oomycetes. This work expands the genome-based understanding of plant-microbe interactions and provides potential leads for efficient and sustainable agriculture through microbiome engineering.}, } @article {pmid29255259, year = {2018}, author = {Chakraborty, M and VanKuren, NW and Zhao, R and Zhang, X and Kalsow, S and Emerson, JJ}, title = {Hidden genetic variation shapes the structure of functional elements in Drosophila.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {20-25}, pmid = {29255259}, issn = {1546-1718}, support = {S10 OD021718/OD/NIH HHS/United States ; T32 EB009418/EB/NIBIB NIH HHS/United States ; S10 RR025496/RR/NCRR NIH HHS/United States ; R01 GM123303/GM/NIGMS NIH HHS/United States ; T32 GM007197/GM/NIGMS NIH HHS/United States ; P30 CA062203/CA/NCI NIH HHS/United States ; }, abstract = {Mutations that add, subtract, rearrange, or otherwise refashion genome structure often affect phenotypes, although the fragmented nature of most contemporary assemblies obscures them. To discover such mutations, we assembled the first new reference-quality genome of Drosophila melanogaster since its initial sequencing. By comparing this new genome to the existing D. melanogaster assembly, we created a structural variant map of unprecedented resolution and identified extensive genetic variation that has remained hidden until now. Many of these variants constitute candidates underlying phenotypic variation, including tandem duplications and a transposable element insertion that amplifies the expression of detoxification-related genes associated with nicotine resistance. The abundance of important genetic variation that still evades discovery highlights how crucial high-quality reference genomes are to deciphering phenotypes.}, } @article {pmid29255258, year = {2018}, author = {Zhu, P and Guo, H and Ren, Y and Hou, Y and Dong, J and Li, R and Lian, Y and Fan, X and Hu, B and Gao, Y and Wang, X and Wei, Y and Liu, P and Yan, J and Ren, X and Yuan, P and Yuan, Y and Yan, Z and Wen, L and Yan, L and Qiao, J and Tang, F}, title = {Single-cell DNA methylome sequencing of human preimplantation embryos.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {12-19}, doi = {10.1038/s41588-017-0007-6}, pmid = {29255258}, issn = {1546-1718}, abstract = {DNA methylation is a crucial layer of epigenetic regulation during mammalian embryonic development 1-3 . Although the DNA methylome of early human embryos has been analyzed 4-6 , some of the key features have not been addressed thus far. Here we performed single-cell DNA methylome sequencing for human preimplantation embryos and found that tens of thousands of genomic loci exhibited de novo DNA methylation. This finding indicates that genome-wide DNA methylation reprogramming during preimplantation development is a dynamic balance between strong global demethylation and drastic focused remethylation. Furthermore, demethylation of the paternal genome is much faster and thorough than that of the maternal genome. From the two-cell to the postimplantation stage, methylation of the paternal genome is consistently lower than that of the maternal genome. We also show that the genetic lineage of early blastomeres can be traced by DNA methylation analysis. Our work paves the way for deciphering the secrets of DNA methylation reprogramming in early human embryos.}, } @article {pmid29255257, year = {2018}, author = {Walker, J and Gao, H and Zhang, J and Aldridge, B and Vickers, M and Higgins, JD and Feng, X}, title = {Sexual-lineage-specific DNA methylation regulates meiosis in Arabidopsis.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {130-137}, doi = {10.1038/s41588-017-0008-5}, pmid = {29255257}, issn = {1546-1718}, abstract = {DNA methylation regulates eukaryotic gene expression and is extensively reprogrammed during animal development. However, whether developmental methylation reprogramming during the sporophytic life cycle of flowering plants regulates genes is presently unknown. Here we report a distinctive gene-targeted RNA-directed DNA methylation (RdDM) activity in the Arabidopsis thaliana male sexual lineage that regulates gene expression in meiocytes. Loss of sexual-lineage-specific RdDM causes mis-splicing of the MPS1 gene (also known as PRD2), thereby disrupting meiosis. Our results establish a regulatory paradigm in which de novo methylation creates a cell-lineage-specific epigenetic signature that controls gene expression and contributes to cellular function in flowering plants.}, } @article {pmid29255255, year = {2018}, author = {Eun, YJ and Ho, PY and Kim, M and LaRussa, S and Robert, L and Renner, LD and Schmid, A and Garner, E and Amir, A}, title = {Archaeal cells share common size control with bacteria despite noisier growth and division.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {148-154}, doi = {10.1038/s41564-017-0082-6}, pmid = {29255255}, issn = {2058-5276}, abstract = {In nature, microorganisms exhibit different volumes spanning six orders of magnitude 1 . Despite their capability to create different sizes, a clonal population in a given environment maintains a uniform size across individual cells. Recent studies in eukaryotic and bacterial organisms showed that this homogeneity in cell size can be accomplished by growing a constant size between two cell cycle events (that is, the adder model 2-6). Demonstration of the adder model led to the hypothesis that this phenomenon is a consequence of convergent evolution. Given that archaeal cells share characteristics with both bacteria and eukaryotes, we investigated whether and how archaeal cells exhibit control over cell size. To this end, we developed a soft-lithography method of growing the archaeal cells to enable quantitative time-lapse imaging and single-cell analysis, which would be useful for other microorganisms. Using this method, we demonstrated that Halobacterium salinarum, a hypersaline-adapted archaeal organism, grows exponentially at the single-cell level and maintains a narrow-size distribution by adding a constant length between cell division events. Interestingly, the archaeal cells exhibited greater variability in cell division placement and exponential growth rate across individual cells in a population relative to those observed in Escherichia coli 6-9 . Here, we present a theoretical framework that explains how these larger fluctuations in archaeal cell cycle events contribute to cell size variability and control.}, } @article {pmid29255254, year = {2018}, author = {Luis, AS and Briggs, J and Zhang, X and Farnell, B and Ndeh, D and Labourel, A and Baslé, A and Cartmell, A and Terrapon, N and Stott, K and Lowe, EC and McLean, R and Shearer, K and Schückel, J and Venditto, I and Ralet, MC and Henrissat, B and Martens, EC and Mosimann, SC and Abbott, DW and Gilbert, HJ}, title = {Dietary pectic glycans are degraded by coordinated enzyme pathways in human colonic Bacteroides.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {210-219}, pmid = {29255254}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; 097907//Wellcome Trust/United Kingdom ; 322820//European Research Council/International ; }, abstract = {The major nutrients available to human colonic Bacteroides species are glycans, exemplified by pectins, a network of covalently linked plant cell wall polysaccharides containing galacturonic acid (GalA). Metabolism of complex carbohydrates by the Bacteroides genus is orchestrated by polysaccharide utilization loci (PULs). In Bacteroides thetaiotaomicron, a human colonic bacterium, the PULs activated by different pectin domains have been identified; however, the mechanism by which these loci contribute to the degradation of these GalA-containing polysaccharides is poorly understood. Here we show that each PUL orchestrates the metabolism of specific pectin molecules, recruiting enzymes from two previously unknown glycoside hydrolase families. The apparatus that depolymerizes the backbone of rhamnogalacturonan-I is particularly complex. This system contains several glycoside hydrolases that trim the remnants of other pectin domains attached to rhamnogalacturonan-I, and nine enzymes that contribute to the degradation of the backbone that makes up a rhamnose-GalA repeating unit. The catalytic properties of the pectin-degrading enzymes are optimized to protect the glycan cues that activate the specific PULs ensuring a continuous supply of inducing molecules throughout growth. The contribution of Bacteroides spp. to metabolism of the pectic network is illustrated by cross-feeding between organisms.}, } @article {pmid29255057, year = {2018}, author = {Wang, F and Yin, Q and Chen, L and Davis, MM}, title = {Bifidobacterium can mitigate intestinal immunopathology in the context of CTLA-4 blockade.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {157-161}, pmid = {29255057}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Antibodies, Neutralizing/adverse effects/pharmacology ; Bifidobacterium/*immunology ; CTLA-4 Antigen/*antagonists & inhibitors/immunology ; Colitis/chemically induced/genetics/*immunology/*therapy ; Mice ; Mice, Transgenic ; Vancomycin/adverse effects/pharmacology ; }, abstract = {Antibodies that attenuate immune tolerance have been used to effectively treat cancer, but they can also trigger severe autoimmunity. To investigate this, we combined anti-CTLA-4 treatment with a standard colitis model to give mice a more severe form of the disease. Pretreatment with an antibiotic, vancomycin, provoked an even more severe, largely fatal form, suggesting that a Gram-positive component of the microbiota had a mitigating effect. We then found that a commonly used probiotic, Bifidobacterium, could largely rescue the mice from immunopathology without an apparent effect on antitumor immunity, and this effect may be dependent on regulatory T cells.}, } @article {pmid29255056, year = {2018}, author = {Yeh, YT and Serrano, R and François, J and Chiu, JJ and Li, YJ and Del Álamo, JC and Chien, S and Lasheras, JC}, title = {Three-dimensional forces exerted by leukocytes and vascular endothelial cells dynamically facilitate diapedesis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {133-138}, pmid = {29255056}, issn = {1091-6490}, support = {R01 HL108735/HL/NHLBI NIH HHS/United States ; R01 HL106579/HL/NHLBI NIH HHS/United States ; T32 HL105373/HL/NHLBI NIH HHS/United States ; R01 HL121365/HL/NHLBI NIH HHS/United States ; R01 GM084227/GM/NIGMS NIH HHS/United States ; }, mesh = {HL-60 Cells ; Human Umbilical Vein Endothelial Cells/cytology/*metabolism ; Humans ; Intercellular Junctions/*metabolism ; Leukocytes/cytology/*metabolism ; *Models, Biological ; Transendothelial and Transepithelial Migration/*physiology ; }, abstract = {Leukocyte transmigration across vessel walls is a critical step in the innate immune response. Upon their activation and firm adhesion to vascular endothelial cells (VECs), leukocytes preferentially extravasate across junctional gaps in the endothelial monolayer (paracellular diapedesis). It has been hypothesized that VECs facilitate paracellular diapedesis by opening their cell-cell junctions in response to the presence of an adhering leukocyte. However, it is unclear how leukocytes interact mechanically with VECs to open the VEC junctions and migrate across the endothelium. In this study, we measured the spatial and temporal evolution of the 3D traction stresses generated by the leukocytes and VECs to elucidate the sequence of mechanical events involved in paracellular diapedesis. Our measurements suggest that the contractile stresses exerted by the leukocytes and the VECs can separately perturb the junctional tensions of VECs to result in the opening of gaps before the initiation of leukocyte transmigration. Decoupling the stresses exerted by the transmigrating leukocytes and the VECs reveals that the leukocytes actively contract the VECs to open a junctional gap and then push themselves across the gap by generating strong stresses that push into the matrix. In addition, we found that diapedesis is facilitated when the tension fluctuations in the VEC monolayer were increased by proinflammatory thrombin treatment. Our findings demonstrate that diapedesis can be mechanically regulated by the transmigrating leukocytes and by proinflammatory signals that increase VEC contractility.}, } @article {pmid29255055, year = {2018}, author = {Liu, S and Li, K and Gao, Y and Liu, X and Chen, W and Ge, W and Feng, Q and Palli, SR and Li, S}, title = {Antagonistic actions of juvenile hormone and 20-hydroxyecdysone within the ring gland determine developmental transitions in Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {139-144}, pmid = {29255055}, issn = {1091-6490}, support = {R01 GM070559/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Corpora Allata/*embryology ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster ; Ecdysterone/*metabolism ; Gene Expression Regulation, Developmental/*physiology ; Juvenile Hormones/genetics/*metabolism ; Kruppel-Like Transcription Factors/genetics/metabolism ; Metamorphosis, Biological/*physiology ; Signal Transduction/*physiology ; }, abstract = {In both vertebrates and insects, developmental transition from the juvenile stage to adulthood is regulated by steroid hormones. In insects, the steroid hormone, 20-hydroxyecdysone (20E), elicits metamorphosis, thus promoting this transition, while the sesquiterpenoid juvenile hormone (JH) antagonizes 20E signaling to prevent precocious metamorphosis during the larval stages. However, not much is known about the mechanisms involved in cross-talk between these two hormones. In this study, we discovered that in the ring gland (RG) of Drosophila larvae, JH and 20E control each other's biosynthesis. JH induces expression of a Krüppel-like transcription factor gene Kr-h1 in the prothoracic gland (PG), a portion of the RG that produces the 20E precursor ecdysone. By reducing both steroidogenesis autoregulation and PG size, high levels of Kr-h1 in the PG inhibit ecdysteriod biosynthesis, thus maintaining juvenile status. JH biosynthesis is prevented by 20E in the corpus allatum, the other portion of the RG that produces JH, to ensure the occurrence of metamorphosis. Hence, antagonistic actions of JH and 20E within the RG determine developmental transitions in Drosophila Our study proposes a mechanism of cross-talk between the two major hormones in the regulation of insect metamorphosis.}, } @article {pmid29255054, year = {2018}, author = {Inman, CS and Manns, JR and Bijanki, KR and Bass, DI and Hamann, S and Drane, DL and Fasano, RE and Kovach, CK and Gross, RE and Willie, JT}, title = {Direct electrical stimulation of the amygdala enhances declarative memory in humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {98-103}, pmid = {29255054}, issn = {1091-6490}, support = {KL2 TR000455/TR/NCATS NIH HHS/United States ; KL2 TR002381/TR/NCATS NIH HHS/United States ; R01 MH100318/MH/NIMH NIH HHS/United States ; F30 MH095491/MH/NIMH NIH HHS/United States ; R01 NS088748/NS/NINDS NIH HHS/United States ; UL1 TR002378/TR/NCATS NIH HHS/United States ; }, mesh = {Adult ; Amygdala/*physiology ; *Deep Brain Stimulation ; Emotions/physiology ; Female ; Hippocampus/physiology ; Humans ; Male ; Memory/*physiology ; Perirhinal Cortex/physiology ; }, abstract = {Emotional events are often remembered better than neutral events, a benefit that many studies have hypothesized to depend on the amygdala's interactions with memory systems. These studies have indicated that the amygdala can modulate memory-consolidation processes in other brain regions such as the hippocampus and perirhinal cortex. Indeed, rodent studies have demonstrated that direct activation of the amygdala can enhance memory consolidation even during nonemotional events. However, the premise that the amygdala causally enhances declarative memory has not been directly tested in humans. Here we tested whether brief electrical stimulation to the amygdala could enhance declarative memory for specific images of neutral objects without eliciting a subjective emotional response. Fourteen epilepsy patients undergoing monitoring of seizures via intracranial depth electrodes viewed a series of neutral object images, half of which were immediately followed by brief, low-amplitude electrical stimulation to the amygdala. Amygdala stimulation elicited no subjective emotional response but led to reliably improved memory compared with control images when patients were given a recognition-memory test the next day. Neuronal oscillations in the amygdala, hippocampus, and perirhinal cortex during this next-day memory test indicated that a neural correlate of the memory enhancement was increased theta and gamma oscillatory interactions between these regions, consistent with the idea that the amygdala prioritizes consolidation by engaging other memory regions. These results show that the amygdala can initiate endogenous memory prioritization processes in the absence of emotional input, addressing a fundamental question and opening a path to future therapies.}, } @article {pmid29255053, year = {2018}, author = {Schopf, JW and Kitajima, K and Spicuzza, MJ and Kudryavtsev, AB and Valley, JW}, title = {SIMS analyses of the oldest known assemblage of microfossils document their taxon-correlated carbon isotope compositions.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {53-58}, pmid = {29255053}, issn = {1091-6490}, mesh = {Archaea/*chemistry ; Australia ; Carbon Isotopes/*analysis ; *Fossils ; *Radiometric Dating ; }, abstract = {Analyses by secondary ion mass spectroscopy (SIMS) of 11 specimens of five taxa of prokaryotic filamentous kerogenous cellular microfossils permineralized in a petrographic thin section of the ∼3,465 Ma Apex chert of northwestern Western Australia, prepared from the same rock sample from which this earliest known assemblage of cellular fossils was described more than two decades ago, show their δ13C compositions to vary systematically taxon to taxon from -31‰ to -39‰. These morphospecies-correlated carbon isotope compositions confirm the biogenicity of the Apex fossils and validate their morphology-based taxonomic assignments. Perhaps most significantly, the δ13C values of each of the five taxa are lower than those of bulk samples of Apex kerogen (-27‰), those of SIMS-measured fossil-associated dispersed particulate kerogen (-27.6‰), and those typical of modern prokaryotic phototrophs (-25 ± 10‰). The SIMS data for the two highest δ13C Apex taxa are consistent with those of extant phototrophic bacteria; those for a somewhat lower δ13C taxon, with nonbacterial methane-producing Archaea; and those for the two lowest δ13C taxa, with methane-metabolizing γ-proteobacteria. Although the existence of both methanogens and methanotrophs has been inferred from bulk analyses of the carbon isotopic compositions of pre-2,500 Ma kerogens, these in situ SIMS analyses of individual microfossils present data interpretable as evidencing the cellular preservation of such microorganisms and are consistent with the near-basal position of the Archaea in rRNA phylogenies.}, } @article {pmid29255052, year = {2018}, author = {Ossó, A and Sutton, R and Shaffrey, L and Dong, B}, title = {Observational evidence of European summer weather patterns predictable from spring.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {59-63}, pmid = {29255052}, issn = {1091-6490}, abstract = {Forecasts of summer weather patterns months in advance would be of great value for a wide range of applications. However, seasonal dynamical model forecasts for European summers have very little skill, particularly for rainfall. It has not been clear whether this low skill reflects inherent unpredictability of summer weather or, alternatively, is a consequence of weaknesses in current forecast systems. Here we analyze atmosphere and ocean observations and identify evidence that a specific pattern of summertime atmospheric circulation--the summer East Atlantic (SEA) pattern--is predictable from the previous spring. An index of North Atlantic sea-surface temperatures in March-April can predict the SEA pattern in July-August with a cross-validated correlation skill above 0.6. Our analyses show that the sea-surface temperatures influence atmospheric circulation and the position of the jet stream over the North Atlantic. The SEA pattern has a particularly strong influence on rainfall in the British Isles, which we find can also be predicted months ahead with a significant skill of 0.56. Our results have immediate application to empirical forecasts of summer rainfall for the United Kingdom, Ireland, and northern France and also suggest that current dynamical model forecast systems have large potential for improvement.}, } @article {pmid29255050, year = {2018}, author = {Nittrouer, CL and Hebl, MR and Ashburn-Nardo, L and Trump-Steele, RCE and Lane, DM and Valian, V}, title = {Gender disparities in colloquium speakers at top universities.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {104-108}, pmid = {29255050}, issn = {1091-6490}, support = {R01 GM088530/GM/NIGMS NIH HHS/United States ; }, mesh = {*Databases, Factual ; Female ; Humans ; Male ; United States ; *Universities ; *Women's Rights ; }, abstract = {Colloquium talks at prestigious universities both create and reflect academic researchers' reputations. Gender disparities in colloquium talks can arise through a variety of mechanisms. The current study examines gender differences in colloquium speakers at 50 prestigious US colleges and universities in 2013-2014. Using archival data, we analyzed 3,652 talks in six academic disciplines. Men were more likely than women to be colloquium speakers even after controlling for the gender and rank of the available speakers. Eliminating alternative explanations (e.g., women declining invitations more often than men), our follow-up data revealed that female and male faculty at top universities reported no differences in the extent to which they (i) valued and (ii) turned down speaking engagements. Additional data revealed that the presence of women as colloquium chairs (and potentially on colloquium committees) increased the likelihood of women appearing as colloquium speakers. Our data suggest that those who invite and schedule speakers serve as gender gatekeepers with the power to create or reduce gender differences in academic reputations.}, } @article {pmid29255049, year = {2018}, author = {Lachat, C and Raneri, JE and Smith, KW and Kolsteren, P and Van Damme, P and Verzelen, K and Penafiel, D and Vanhove, W and Kennedy, G and Hunter, D and Odhiambo, FO and Ntandou-Bouzitou, G and De Baets, B and Ratnasekera, D and Ky, HT and Remans, R and Termote, C}, title = {Dietary species richness as a measure of food biodiversity and nutritional quality of diets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {127-132}, pmid = {29255049}, issn = {1091-6490}, mesh = {Child ; Child, Preschool ; *Eating ; Female ; *Food Preferences ; Humans ; Infant ; Male ; *Micronutrients ; *Nutritive Value ; *Rural Population ; }, abstract = {Biodiversity is key for human and environmental health. Available dietary and ecological indicators are not designed to assess the intricate relationship between food biodiversity and diet quality. We applied biodiversity indicators to dietary intake data from and assessed associations with diet quality of women and young children. Data from 24-hour diet recalls (55% in the wet season) of n = 6,226 participants (34% women) in rural areas from seven low- and middle-income countries were analyzed. Mean adequacies of vitamin A, vitamin C, folate, calcium, iron, and zinc and diet diversity score (DDS) were used to assess diet quality. Associations of biodiversity indicators with nutrient adequacy were quantified using multilevel models, receiver operating characteristic curves, and test sensitivity and specificity. A total of 234 different species were consumed, of which <30% were consumed in more than one country. Nine species were consumed in all countries and provided, on average, 61% of total energy intake and a significant contribution of micronutrients in the wet season. Compared with Simpson's index of diversity and functional diversity, species richness (SR) showed stronger associations and better diagnostic properties with micronutrient adequacy. For every additional species consumed, dietary nutrient adequacy increased by 0.03 (P < 0.001). Diets with higher nutrient adequacy were mostly obtained when both SR and DDS were maximal. Adding SR to the minimum cutoff for minimum diet diversity improved the ability to detect diets with higher micronutrient adequacy in women but not in children. Dietary SR is recommended as the most appropriate measure of food biodiversity in diets.}, } @article {pmid29255048, year = {2018}, author = {Baek, C and Sageman-Furnas, AO and Jawed, MK and Reis, PM}, title = {Form finding in elastic gridshells.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {75-80}, pmid = {29255048}, issn = {1091-6490}, abstract = {Elastic gridshells comprise an initially planar network of elastic rods that are actuated into a shell-like structure by loading their extremities. The resulting actuated form derives from the elastic buckling of the rods subjected to inextensibility. We study elastic gridshells with a focus on the rational design of the final shapes. Our precision desktop experiments exhibit complex geometries, even from seemingly simple initial configurations and actuation processes. The numerical simulations capture this nonintuitive behavior with excellent quantitative agreement, allowing for an exploration of parameter space that reveals multistable states. We then turn to the theory of smooth Chebyshev nets to address the inverse design of hemispherical elastic gridshells. The results suggest that rod inextensibility, not elastic response, dictates the zeroth-order shape of an actuated elastic gridshell. As it turns out, this is the shape of a common household strainer. Therefore, the geometry of Chebyshev nets can be further used to understand elastic gridshells. In particular, we introduce a way to quantify the intrinsic shape of the empty, but enclosed regions, which we then use to rationalize the nonlocal deformation of elastic gridshells to point loading. This justifies the observed difficulty in form finding. Nevertheless, we close with an exploration of concatenating multiple elastic gridshell building blocks.}, } @article {pmid29255047, year = {2018}, author = {Jee, AY and Dutta, S and Cho, YK and Tlusty, T and Granick, S}, title = {Enzyme leaps fuel antichemotaxis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {14-18}, pmid = {29255047}, issn = {1091-6490}, mesh = {Acetylcholinesterase/*chemistry ; Animals ; *Electrophorus ; Fish Proteins/*chemistry ; Urease/*chemistry ; }, abstract = {There is mounting evidence that enzyme diffusivity is enhanced when the enzyme is catalytically active. Here, using superresolution microscopy [stimulated emission-depletion fluorescence correlation spectroscopy (STED-FCS)], we show that active enzymes migrate spontaneously in the direction of lower substrate concentration ("antichemotaxis") by a process analogous to the run-and-tumble foraging strategy of swimming microorganisms and our theory quantifies the mechanism. The two enzymes studied, urease and acetylcholinesterase, display two families of transit times through subdiffraction-sized focus spots, a diffusive mode and a ballistic mode, and the latter transit time is close to the inverse rate of catalytic turnover. This biochemical information-processing algorithm may be useful to design synthetic self-propelled swimmers and nanoparticles relevant to active materials. Executed by molecules lacking the decision-making circuitry of microorganisms, antichemotaxis by this run-and-tumble process offers the biological function to homogenize product concentration, which could be significant in situations when the reactant concentration varies from spot to spot.}, } @article {pmid29255046, year = {2018}, author = {Branca, RT and McCallister, A and Yuan, H and Aghajanian, A and Faber, JE and Weimer, N and Buchanan, R and Floyd, CS and Antonacci, M and Zhang, L and Burant, A}, title = {Accurate quantification of brown adipose tissue mass by xenon-enhanced computed tomography.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {174-179}, pmid = {29255046}, issn = {1091-6490}, support = {P30 DK056350/DK/NIDDK NIH HHS/United States ; R01 DK108231/DK/NIDDK NIH HHS/United States ; }, mesh = {Adipose Tissue, Brown/*diagnostic imaging ; Animals ; Macaca ; Mice, Obese ; Positron Emission Tomography Computed Tomography/instrumentation/*methods ; *Xenon ; }, abstract = {Detection and quantification of brown adipose tissue (BAT) mass remains a major challenge, as current tomographic imaging techniques are either nonspecific or lack the necessary resolution to quantify BAT mass, especially in obese phenotypes, in which this tissue may be present but inactive. Here, we report quantification of BAT mass by xenon-enhanced computed tomography. We show that, during stimulation of BAT thermogenesis, the lipophilic gas xenon preferentially accumulates in BAT, leading to a radiodensity enhancement comparable to that seen in the lungs. This enhancement is mediated by a selective reduction in BAT vascular resistance, which greatly increases vascular perfusion of BAT. This enhancement enables precise identification and quantification of BAT mass not only in lean, but also in obese, mouse phenotypes, in which this tissue is invisible to conventional tomographic imaging techniques. The method is developed and validated in rodents and then applied in macaques to assess its feasibility in larger species.}, } @article {pmid29255045, year = {2018}, author = {}, title = {Correction for Larsen and Noack, Identifying the landscape drivers of agricultural insecticide use leveraging evidence from 100,000 fields.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E112}, doi = {10.1073/pnas.1721250115}, pmid = {29255045}, issn = {1091-6490}, } @article {pmid29255044, year = {2018}, author = {Sanjak, JS and Sidorenko, J and Robinson, MR and Thornton, KR and Visscher, PM}, title = {Evidence of directional and stabilizing selection in contemporary humans.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {151-156}, pmid = {29255044}, issn = {1091-6490}, support = {MC_QA137853//Medical Research Council/United Kingdom ; R01 GM115564/GM/NIGMS NIH HHS/United States ; }, mesh = {*Biological Evolution ; Female ; Humans ; Male ; Middle Aged ; *Models, Genetic ; *Phenotype ; *Selection, Genetic ; United Kingdom ; }, abstract = {Modern molecular genetic datasets, primarily collected to study the biology of human health and disease, can be used to directly measure the action of natural selection and reveal important features of contemporary human evolution. Here we leverage the UK Biobank data to test for the presence of linear and nonlinear natural selection in a contemporary population of the United Kingdom. We obtain phenotypic and genetic evidence consistent with the action of linear/directional selection. Phenotypic evidence suggests that stabilizing selection, which acts to reduce variance in the population without necessarily modifying the population mean, is widespread and relatively weak in comparison with estimates from other species.}, } @article {pmid29255043, year = {2018}, author = {Wu, H and Miller, KJ and Blumenfeld, Z and Williams, NR and Ravikumar, VK and Lee, KE and Kakusa, B and Sacchet, MD and Wintermark, M and Christoffel, DJ and Rutt, BK and Bronte-Stewart, H and Knutson, B and Malenka, RC and Halpern, CH}, title = {Closing the loop on impulsivity via nucleus accumbens delta-band activity in mice and man.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {192-197}, pmid = {29255043}, issn = {1091-6490}, support = {K12 NS080223/NS/NINDS NIH HHS/United States ; P41 EB015891/EB/NIBIB NIH HHS/United States ; UL1 TR001085/TR/NCATS NIH HHS/United States ; }, mesh = {Animals ; Consummatory Behavior/*physiology ; Delta Rhythm/*physiology ; Female ; Humans ; Male ; Mice ; Nucleus Accumbens/*physiology ; }, abstract = {Reward hypersensitization is a common feature of neuropsychiatric disorders, manifesting as impulsivity for anticipated incentives. Temporally specific changes in activity within the nucleus accumbens (NAc), which occur during anticipatory periods preceding consummatory behavior, represent a critical opportunity for intervention. However, no available therapy is capable of automatically sensing and therapeutically responding to this vulnerable moment in time when anticipation-related neural signals may be present. To identify translatable biomarkers for an off-the-shelf responsive neurostimulation system, we record local field potentials from the NAc of mice and a human anticipating conventional rewards. We find increased power in 1- to 4-Hz oscillations predominate during reward anticipation, which can effectively trigger neurostimulation that reduces consummatory behavior in mice sensitized to highly palatable food. Similar oscillations are present in human NAc during reward anticipation, highlighting the translational potential of our findings in the development of a treatment for a major unmet need.}, } @article {pmid29255042, year = {2018}, author = {Praske, E and Otkjær, RV and Crounse, JD and Hethcox, JC and Stoltz, BM and Kjaergaard, HG and Wennberg, PO}, title = {Atmospheric autoxidation is increasingly important in urban and suburban North America.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {64-69}, pmid = {29255042}, issn = {1091-6490}, abstract = {Gas-phase autoxidation-regenerative peroxy radical formation following intramolecular hydrogen shifts-is known to be important in the combustion of organic materials. The relevance of this chemistry in the oxidation of organics in the atmosphere has received less attention due, in part, to the lack of kinetic data at relevant temperatures. Here, we combine computational and experimental approaches to investigate the rate of autoxidation for organic peroxy radicals (RO2) produced in the oxidation of a prototypical atmospheric pollutant, n-hexane. We find that the reaction rate depends critically on the molecular configuration of the RO2 radical undergoing hydrogen transfer (H-shift). RO2 H-shift rate coefficients via transition states involving six- and seven-membered rings (1,5 and 1,6 H-shifts, respectively) of α-OH hydrogens (HOC-H) formed in this system are of order 0.1 s-1 at 296 K, while the 1,4 H-shift is calculated to be orders of magnitude slower. Consistent with H-shift reactions over a substantial energetic barrier, we find that the rate coefficients of these reactions increase rapidly with temperature and exhibit a large, primary, kinetic isotope effect. The observed H-shift rate coefficients are sufficiently fast that, as a result of ongoing NO x emission reductions, autoxidation is now competing with bimolecular chemistry even in the most polluted North American cities, particularly during summer afternoons when NO levels are low and temperatures are elevated.}, } @article {pmid29255041, year = {2018}, author = {Raymond, DD and Bajic, G and Ferdman, J and Suphaphiphat, P and Settembre, EC and Moody, MA and Schmidt, AG and Harrison, SC}, title = {Conserved epitope on influenza-virus hemagglutinin head defined by a vaccine-induced antibody.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {168-173}, pmid = {29255041}, issn = {1091-6490}, support = {P01 AI089618/AI/NIAID NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; S10 RR029205/RR/NCRR NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Antibodies, Monoclonal/*immunology ; Antibodies, Viral/*immunology ; Epitopes/genetics/*immunology ; Hemagglutinin Glycoproteins, Influenza Virus/genetics/*immunology ; Humans ; *Immunologic Memory ; Influenza Vaccines/administration & dosage/genetics/*immunology ; }, abstract = {Circulating influenza viruses evade neutralization in their human hosts by acquiring escape mutations at epitopes of prevalent antibodies. A goal for next-generation influenza vaccines is to reduce escape likelihood by selectively eliciting antibodies recognizing conserved surfaces on the viral hemagglutinin (HA). The receptor-binding site (RBS) on the HA "head" and a region near the fusion peptide on the HA "stem" are two such sites. We describe here a human antibody clonal lineage, designated CL6649, members of which bind a third conserved site ("lateral patch") on the side of the H1-subtype, HA head. A crystal structure of HA with bound Fab6649 shows the conserved antibody footprint. The site was invariant in isolates from 1977 (seasonal) to 2012 (pdm2009); antibodies in CL6649 recognize HAs from the entire period. In 2013, human H1 viruses acquired mutations in this epitope that were retained in subsequent seasons, prompting modification of the H1 vaccine component in 2017. The mutations inhibit Fab6649 binding. We infer from the rapid spread of these mutations in circulating H1 influenza viruses that the previously subdominant, conserved lateral patch had become immunodominant for individuals with B-cell memory imprinted by earlier H1 exposure. We suggest that introduction of the pdm2009 H1 virus, to which most of the broadly prevalent, neutralizing antibodies did not bind, conferred a selective advantage in the immune systems of infected hosts to recall of memory B cells that recognized the lateral patch, the principal exposed epitope that did not change when pdm2009 displaced previous seasonal H1 viruses.}, } @article {pmid29255040, year = {2018}, author = {Gaydosh, L and Schorpp, KM and Chen, E and Miller, GE and Harris, KM}, title = {College completion predicts lower depression but higher metabolic syndrome among disadvantaged minorities in young adulthood.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {109-114}, pmid = {29255040}, issn = {1091-6490}, support = {F32 HD084117/HD/NICHD NIH HHS/United States ; P01 HD031921/HD/NICHD NIH HHS/United States ; P2C HD050924/HD/NICHD NIH HHS/United States ; T32 HD007168/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Depression/*epidemiology ; *Education, Professional ; Female ; Humans ; Male ; Metabolic Syndrome/*epidemiology ; *Minority Groups ; Young Adult ; }, abstract = {Individuals with higher educational attainment live healthier and longer lives. However, not everyone benefits equally from higher education. In particular, the black-white gap in life expectancy is greater at higher levels of educational attainment. Furthermore, recent research suggests that disadvantaged African Americans in the rural Southeast who attend college have worse physical health than their similarly disadvantaged peers who do not attend college. The extent to which this pattern generalizes to a nationally representative, mixed-race sample is unknown. Using data from the National Longitudinal Study of Adolescent to Adult Health, we test whether the health benefits associated with college completion vary by level of childhood disadvantage for depression and metabolic syndrome in young adulthood, across race/ethnicity. We find uniform lower depression associated with college completion regardless of childhood disadvantage, and across non-Hispanic white, non-Hispanic black, and Hispanic young adults. College completion is associated with lower metabolic syndrome for whites across all levels of childhood disadvantage. In contrast, college completion is associated with higher metabolic syndrome among black and Hispanic young adults from disadvantaged childhood environments. Our findings suggest that, for minorities from disadvantaged backgrounds, finishing college pays substantial dividends for mental health but simultaneously exacts costs with regard to physical health. This pattern contrasts starkly with whites and minorities from more privileged backgrounds, for whom college completion is associated with benefits to both mental and physical health. These results suggest that racial disparities in health may persist in part because the health of upwardly mobile minorities is compromised in young adulthood.}, } @article {pmid29255039, year = {2018}, author = {Shrout, PE and Stadler, G and Lane, SP and McClure, MJ and Jackson, GL and Clavél, FD and Iida, M and Gleason, MEJ and Xu, JH and Bolger, N}, title = {Initial elevation bias in subjective reports.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E15-E23}, pmid = {29255039}, issn = {1091-6490}, mesh = {Adult ; Female ; Humans ; Male ; *Self Report ; *Self-Assessment ; }, abstract = {People's reports of their thoughts, feelings, and behaviors are used in many fields of biomedical and social science. When these states have been studied over time, researchers have often observed an unpredicted and puzzling decrease with repeated assessment. When noted, this pattern has been called an "attenuation effect," suggesting that the effect is due to bias in later reports. However, the pattern could also be consistent with an initial elevation bias. We present systematic, experimental investigations of this effect in four field studies (study 1: n = 870; study 2: n = 246; study 3: n = 870; study 4: n = 141). Findings show clear support for an initial elevation bias rather than a later decline. This bias is larger for reports of internal states than for behaviors and for negative mental states and physical symptoms than for positive states. We encourage increased awareness and investigation of this initial elevation bias in all research using subjective reports.}, } @article {pmid29255037, year = {2018}, author = {Huang, C and Quinn, D and Suresh, S and Hsia, KJ}, title = {Controlled molecular self-assembly of complex three-dimensional structures in soft materials.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {70-74}, pmid = {29255037}, issn = {1091-6490}, support = {R01 HD086325/HD/NICHD NIH HHS/United States ; }, mesh = {*Biomimetic Materials/chemical synthesis/chemistry ; Humans ; *Hydrogels/chemical synthesis/chemistry ; Porosity ; *Tissue Engineering ; Tissue Scaffolds/*chemistry ; }, abstract = {Many applications in tissue engineering, flexible electronics, and soft robotics call for approaches that are capable of producing complex 3D architectures in soft materials. Here we present a method using molecular self-assembly to generate hydrogel-based 3D architectures that resembles the appealing features of the bottom-up process in morphogenesis of living tissues. Our strategy effectively utilizes the three essential components dictating living tissue morphogenesis to produce complex 3D architectures: modulation of local chemistry, material transport, and mechanics, which can be engineered by controlling the local distribution of polymerization inhibitor (i.e., oxygen), diffusion of monomers/cross-linkers through the porous structures of cross-linked polymer network, and mechanical constraints, respectively. We show that oxygen plays a role in hydrogel polymerization which is mechanistically similar to the role of growth factors in tissue growth, and the continued growth of hydrogel enabled by diffusion of monomers/cross-linkers into the porous hydrogel similar to the mechanisms of tissue growth enabled by material transport. The capability and versatility of our strategy are demonstrated through biomimetics of tissue morphogenesis for both plants and animals, and its application to generate other complex 3D architectures. Our technique opens avenues to studying many growth phenomena found in nature and generating complex 3D structures to benefit diverse applications.}, } @article {pmid29255036, year = {2018}, author = {He, X and Sun, Y and Lei, N and Fan, X and Zhang, C and Wang, Y and Zheng, K and Zhang, D and Pan, W}, title = {MicroRNA-351 promotes schistosomiasis-induced hepatic fibrosis by targeting the vitamin D receptor.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {180-185}, pmid = {29255036}, issn = {1091-6490}, mesh = {Animals ; Hepatic Stellate Cells/*immunology/pathology ; Interferon-gamma/immunology ; Liver/*immunology/parasitology/pathology ; Liver Cirrhosis/*immunology/pathology/therapy ; Male ; Mice ; Mice, Inbred BALB C ; MicroRNAs/*immunology ; Receptors, Calcitriol/*immunology ; Schistosoma/*immunology ; Schistosomiasis/*immunology/pathology/therapy ; }, abstract = {Aberrant expression of microRNAs (miRNAs) underlies a spectrum of human diseases including organ fibrosis, and hepatic stellate cells (HSCs) are the main effectors of hepatic fibrosis. Here, we showed that the expression of host miR-351 in HSCs was markedly reduced during the early stage of Schistosoma infection. However, this expression was significantly increased during the later stage of infection (after 52 d of infection). The elevated levels of miR-351 promoted hepatic fibrosis by targeting the vitamin D receptor (VDR), which is an antagonist of SMAD signaling. Importantly, efficient and sustained inhibition of miR-351 in liver tissues using the highly hepatotropic recombinant adeno-associated virus serotype 8 (rAAV8), alleviated the hepatic fibrosis, partially protecting the host from lethal schistosomiasis. In addition, we found that miR-351 is negatively regulated by IFN-γ in HSCs during infection. At the early stage of infection, the elevated levels of IFN-γ inhibited the expression of miR-351 in HSCs through activation of signal transducer and activator of transcription 1 and induction of IFN regulatory factor 2, which binds the promotor of pre-miR-351 Our study provides insights into the mechanisms by which miR-351 regulates schistosomiasis hepatic fibrosis and highlights the potential of rAAV8-mediated miR-351 inhibition as a therapeutic intervention for fibrotic diseases.}, } @article {pmid29255035, year = {2018}, author = {Wang, Y and Sosinowski, T and Novikov, A and Crawford, F and Neau, DB and Yang, J and Kwok, WW and Marrack, P and Kappler, JW and Dai, S}, title = {C-terminal modification of the insulin B:11-23 peptide creates superagonists in mouse and human type 1 diabetes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {162-167}, pmid = {29255035}, issn = {1091-6490}, support = {S10 RR029205/RR/NCRR NIH HHS/United States ; R01 AI018785/AI/NIAID NIH HHS/United States ; P41 GM103403/GM/NIGMS NIH HHS/United States ; R01 DK032083/DK/NIDDK NIH HHS/United States ; KL2 TR001080/TR/NCATS NIH HHS/United States ; R37 AI018785/AI/NIAID NIH HHS/United States ; P30 GM124165/GM/NIGMS NIH HHS/United States ; T32 AI074491/AI/NIAID NIH HHS/United States ; R37 DK032083/DK/NIDDK NIH HHS/United States ; P01 AI118688/AI/NIAID NIH HHS/United States ; R56 AI018785/AI/NIAID NIH HHS/United States ; R01 ES025797/ES/NIEHS NIH HHS/United States ; P30 DK017047/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; *Diabetes Mellitus, Type 1/genetics/immunology ; *Epitopes/chemistry/genetics/immunology ; *HLA-DQ Antigens/chemistry/genetics/immunology ; *Histocompatibility Antigens Class II/chemistry/genetics/immunology ; Humans ; *Insulin/chemistry/genetics/immunology ; Mice ; Mice, Inbred NOD ; Protein Binding ; Protein Processing, Post-Translational/*immunology ; }, abstract = {A polymorphism at β57 in some major histocompatibility complex class II (MHCII) alleles of rodents and humans is associated with a high risk for developing type 1 diabetes (T1D). However, a highly diabetogenic insulin B chain epitope within the B:9-23 peptide is presented poorly by these alleles to a variety of mouse and human CD4 T cells isolated from either nonobese diabetic (NOD) mice or humans with T1D. We have shown for both species that mutations at the C-terminal end of this epitope dramatically improve presentation to these T cells. Here we present the crystal structures of these mutated peptides bound to mouse IAg7 and human HLA-DQ8 that show how the mutations function to improve T-cell activation. In both peptide binding grooves, the mutation of B:22R to E in the peptide changes a highly unfavorable side chain for the p9 pocket to an optimal one that is dependent on the β57 polymorphism, accounting for why these peptides bind much better to these MHCIIs. Furthermore, a second mutation of the adjacent B:21 (E to G) removes a side chain from the surface of the complex that is highly unfavorable for a subset of NOD mouse CD4 cells, thereby greatly enhancing their response to the complex. These results point out the similarities between the mouse and human responses to this B chain epitope in T1D and suggest there may be common posttranslational modifications at the C terminus of the peptide in vivo to create the pathogenic epitopes in both species.}, } @article {pmid29255034, year = {2018}, author = {Yan, GH and Wang, K and Shao, Z and Luo, L and Song, ZM and Chen, J and Jin, R and Deng, X and Wang, H and Cao, Z and Liu, Y and Cao, A}, title = {Artificial antibody created by conformational reconstruction of the complementary-determining region on gold nanoparticles.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E34-E43}, pmid = {29255034}, issn = {1091-6490}, mesh = {Antibodies, Monoclonal/*chemistry ; Complementarity Determining Regions/*chemistry ; Gold/*chemistry ; Metal Nanoparticles/*chemistry ; Protein Conformation ; }, abstract = {To impart biomedical functions to nanoparticles (NPs), the common approach is to conjugate functional groups onto NPs by dint of the functions of those groups per se. It is still beyond current reach to create protein-like specific interactions and functions on NPs by conformational engineering of nonfunctional groups on NPs. Here, we develop a conformational engineering method to create an NP-based artificial antibody, denoted "Goldbody," through conformational reconstruction of the complementary-determining regions (CDRs) of natural antibodies on gold NPs (AuNPs). The seemingly insurmountable task of controlling the conformation of the CDR loops, which are flexible and nonfunctional in the free form, was accomplished unexpectedly in a simple way. Upon anchoring both terminals of the free CDR loops on AuNPs, we managed to reconstruct the "active" conformation of the CDR loops by tuning the span between the two terminals and, as a result, the original specificity was successfully reconstructed on the AuNPs. Two Goldbodies have been created by this strategy to specifically bind with hen egg white lysozyme and epidermal growth factor receptor, with apparent affinities several orders of magnitude stronger than that of the original natural antibodies. Our work demonstrates that it is possible to create protein-like functions on NPs in a protein-like way, namely by tuning flexible surface groups to the correct conformation. Given the apparent merits, including good stability, of Goldbodies, we anticipate that a category of Goldbodies could be created to target different antigens and thus used as substitutes for natural antibodies in various applications.}, } @article {pmid29255033, year = {2018}, author = {Ragazzon, G and Schäfer, C and Franchi, P and Silvi, S and Colasson, B and Lucarini, M and Credi, A}, title = {Remote electrochemical modulation of pKa in a rotaxane by co-conformational allostery.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {38}, pages = {9385-9390}, pmid = {29255033}, issn = {1091-6490}, support = {692981//European Research Council/International ; }, mesh = {Binding Sites ; Electric Stimulation ; Electrochemical Techniques/*methods ; Electron Transport ; Energy Transfer ; *Models, Chemical ; *Molecular Conformation ; Molecular Structure ; Protons ; Rotaxanes/*chemistry ; }, abstract = {Allosteric control, one of Nature's most effective ways to regulate functions in biomolecular machinery, involves the transfer of information between distant sites. The mechanistic details of such a transfer are still an object of intensive investigation and debate, and the idea that intramolecular communication could be enabled by dynamic processes is gaining attention as a complement to traditional explanations. Mechanically interlocked molecules, owing to the particular kind of connection between their components and the resulting dynamic behavior, are attractive systems to investigate allosteric mechanisms and exploit them to develop functionalities with artificial species. We show that the pKa of an ammonium site located on the axle component of a [2]rotaxane can be reversibly modulated by changing the affinity of a remote recognition site for the interlocked crown ether ring through electrochemical stimulation. The use of a reversible ternary redox switch enables us to set the pKa to three different values, encompassing more than seven units. Our results demonstrate that in the axle the two sites do not communicate, and that in the rotaxane the transfer of information between them is made possible by the shuttling of the ring, that is, by a dynamic intramolecular process. The investigated coupling of electron- and proton-transfer reactions is reminiscent of the operation of the protein complex I of the respiratory chain.}, } @article {pmid29255032, year = {2018}, author = {Kim, SE and Behr, MK and Ba, D and Brown, EN}, title = {State-space multitaper time-frequency analysis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E5-E14}, pmid = {29255032}, issn = {1091-6490}, support = {R01 GM104948/GM/NIGMS NIH HHS/United States ; }, mesh = {*Algorithms ; Humans ; *Models, Theoretical ; }, abstract = {Time series are an important data class that includes recordings ranging from radio emissions, seismic activity, global positioning data, and stock prices to EEG measurements, vital signs, and voice recordings. Rapid growth in sensor and recording technologies is increasing the production of time series data and the importance of rapid, accurate analyses. Time series data are commonly analyzed using time-varying spectral methods to characterize their nonstationary and often oscillatory structure. Current methods provide local estimates of data features. However, they do not offer a statistical inference framework that applies to the entire time series. The important advances that we report are state-space multitaper (SS-MT) methods, which provide a statistical inference framework for time-varying spectral analysis of nonstationary time series. We model nonstationary time series as a sequence of second-order stationary Gaussian processes defined on nonoverlapping intervals. We use a frequency-domain random-walk model to relate the spectral representations of the Gaussian processes across intervals. The SS-MT algorithm efficiently computes spectral updates using parallel 1D complex Kalman filters. An expectation-maximization algorithm computes static and dynamic model parameter estimates. We test the framework in time-varying spectral analyses of simulated time series and EEG recordings from patients receiving general anesthesia. Relative to standard multitaper (MT), SS-MT gave enhanced spectral resolution and noise reduction ([Formula: see text]10 dB) and allowed statistical comparisons of spectral properties among arbitrary time series segments. SS-MT also extracts time-domain estimates of signal components. The SS-MT paradigm is a broadly applicable, empirical Bayes' framework for statistical inference that can help ensure accurate, reproducible findings from nonstationary time series analyses.}, } @article {pmid29255031, year = {2018}, author = {Bowling, DL and Purves, D and Gill, KZ}, title = {Vocal similarity predicts the relative attraction of musical chords.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {216-221}, pmid = {29255031}, issn = {1091-6490}, mesh = {Adolescent ; Adult ; Female ; Humans ; Male ; *Music ; Pitch Perception/*physiology ; *Singing ; }, abstract = {Musical chords are combinations of two or more tones played together. While many different chords are used in music, some are heard as more attractive (consonant) than others. We have previously suggested that, for reasons of biological advantage, human tonal preferences can be understood in terms of the spectral similarity of tone combinations to harmonic human vocalizations. Using the chromatic scale, we tested this theory further by assessing the perceived consonance of all possible dyads, triads, and tetrads within a single octave. Our results show that the consonance of chords is predicted by their relative similarity to voiced speech sounds. These observations support the hypothesis that the relative attraction of musical tone combinations is due, at least in part, to the biological advantages that accrue from recognizing and responding to conspecific vocal stimuli.}, } @article {pmid29255029, year = {2018}, author = {Mouri, K and Sagai, T and Maeno, A and Amano, T and Toyoda, A and Shiroishi, T}, title = {Enhancer adoption caused by genomic insertion elicits interdigital Shh expression and syndactyly in mouse.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1021-1026}, pmid = {29255029}, issn = {1091-6490}, mesh = {Animals ; *Enhancer Elements, Genetic ; Gene Expression Regulation, Developmental ; Genetic Linkage ; Glycoproteins/genetics ; Hedgehog Proteins/*genetics/metabolism ; Intercellular Signaling Peptides and Proteins/genetics ; Mice ; Mice, Inbred C57BL ; Mice, Inbred ICR ; Mice, Mutant Strains ; Mice, Transgenic ; Mutagenesis, Insertional ; Mutation ; Phenotype ; Syndactyly/embryology/*genetics/metabolism ; }, abstract = {Acquisition of new cis-regulatory elements (CREs) can cause alteration of developmental gene regulation and may introduce morphological novelty in evolution. Although structural variation in the genome generated by chromosomal rearrangement is one possible source of new CREs, only a few examples are known, except for cases of retrotransposition. In this study, we show the acquisition of novel regulatory sequences as a result of large genomic insertion in the spontaneous mouse mutation Hammer toe (Hm). Hm mice exhibit syndactyly with webbing, due to suppression of interdigital cell death in limb development. We reveal that, in the Hm genome, a 150-kb noncoding DNA fragment from chromosome 14 is inserted into the region upstream of the Sonic hedgehog (Shh) promoter in chromosome 5. Phenotyping of mouse embryos with a series of CRISPR/Cas9-aided partial deletion of the 150-kb insert clearly indicated that two different regions are necessary for the syndactyly phenotype of Hm We found that each of the two regions contains at least one enhancer for interdigital regulation. These results show that a set of enhancers brought by the large genomic insertion elicits the interdigital Shh expression and the Hm phenotype. Transcriptome analysis indicates that ectopic expression of Shh up-regulates Chordin (Chrd) that antagonizes bone morphogenetic protein signaling in the interdigital region. Indeed, Chrd-overexpressing transgenic mice recapitulated syndactyly with webbing. Thus, the Hm mutation provides an insight into enhancer acquisition as a source of creation of novel gene regulation.}, } @article {pmid29255028, year = {2018}, author = {Fletcher, J and Vidal-Fernandez, M and Wolfe, B}, title = {Dynamic and heterogeneous effects of sibling death on children's outcomes.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {115-120}, pmid = {29255028}, issn = {1091-6490}, support = {P2C HD047873/HD/NICHD NIH HHS/United States ; }, mesh = {Adolescent ; *Adolescent Development ; Adult ; *Attitude to Death ; Child ; *Child Development ; *Cognition ; *Death ; *Emotions ; Female ; Humans ; Male ; *Siblings ; United States ; }, abstract = {This paper explores the effects of experiencing the death of a sibling on children's developmental outcomes. Recent work has shown that experiencing a sibling death is common and long-term effects are large. We extend understanding of these effects by estimating dynamic effects on surviving siblings' cognitive and socioemotional outcomes, as well as emotional and cognitive support by parents. Using the Children of the National Longitudinal Survey of Youth 1979 (CNLSY79), we find large initial effects on cognitive and noncognitive outcomes that decline over time. We also provide evidence that the effects are larger if the surviving child is older and less prominent if the deceased child was either disabled or an infant, suggesting sensitive periods of exposure. Auxiliary results show that parental investments in the emotional support of surviving children decline following the death of their child.}, } @article {pmid29255027, year = {2018}, author = {Radl, D and Chiacchiaretta, M and Lewis, RG and Brami-Cherrier, K and Arcuri, L and Borrelli, E}, title = {Differential regulation of striatal motor behavior and related cellular responses by dopamine D2L and D2S isoforms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {198-203}, pmid = {29255027}, issn = {1091-6490}, support = {R21 DA033554/DA/NIDA NIH HHS/United States ; }, mesh = {Animals ; Cocaine-Related Disorders/genetics/*metabolism/physiopathology ; Corpus Striatum/*metabolism/physiopathology ; Dopamine/metabolism ; Mice ; Mice, Knockout ; *Motor Activity ; Protein Isoforms/genetics/metabolism ; Receptors, Dopamine D2/genetics/*metabolism ; *Synaptic Potentials ; }, abstract = {The dopamine D2 receptor (D2R) is a major component of the dopamine system. D2R-mediated signaling in dopamine neurons is involved in the presynaptic regulation of dopamine levels. Postsynaptically, i.e., in striatal neurons, D2R signaling controls complex functions such as motor activity through regulation of cell firing and heterologous neurotransmitter release. The presence of two isoforms, D2L and D2S, which are generated by a mechanism of alternative splicing of the Drd2 gene, raises the question of whether both isoforms may equally control presynaptic and postsynaptic events. Here, we addressed this question by comparing behavioral and cellular responses of mice with the selective ablation of either D2L or D2S isoform. We establish that the presence of either D2L or D2S can support postsynaptic functions related to the control of motor activity in basal conditions. On the contrary, absence of D2S but not D2L prevents the inhibition of tyrosine hydroxylase phosphorylation and, thereby, of dopamine synthesis, supporting a major presynaptic role for D2S. Interestingly, boosting dopamine signaling in the striatum by acute cocaine administration reveals that absence of D2L, but not of D2S, strongly impairs the motor and cellular response to the drug, in a manner similar to the ablation of both isoforms. These results suggest that when the dopamine system is challenged, D2L signaling is required for the control of striatal circuits regulating motor activity. Thus, our findings show that D2L and D2S share similar functions in basal conditions but not in response to stimulation of the dopamine system.}, } @article {pmid29255026, year = {2018}, author = {Strother, JA and Wu, ST and Rogers, EM and Eliason, JLM and Wong, AM and Nern, A and Reiser, MB}, title = {Behavioral state modulates the ON visual motion pathway of Drosophila.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E102-E111}, pmid = {29255026}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Behavior, Animal/*physiology ; Drosophila ; Motor Activity/*physiology ; Neurons/cytology/*metabolism ; Octopamine/*metabolism ; }, abstract = {The behavioral state of an animal can dynamically modulate visual processing. In flies, the behavioral state is known to alter the temporal tuning of neurons that carry visual motion information into the central brain. However, where this modulation occurs and how it tunes the properties of this neural circuit are not well understood. Here, we show that the behavioral state alters the baseline activity levels and the temporal tuning of the first directionally selective neuron in the ON motion pathway (T4) as well as its primary input neurons (Mi1, Tm3, Mi4, Mi9). These effects are especially prominent in the inhibitory neuron Mi4, and we show that central octopaminergic neurons provide input to Mi4 and increase its excitability. We further show that octopamine neurons are required for sustained behavioral responses to fast-moving, but not slow-moving, visual stimuli in walking flies. These results indicate that behavioral-state modulation acts directly on the inputs to the directionally selective neurons and supports efficient neural coding of motion stimuli.}, } @article {pmid29255025, year = {2018}, author = {Nam, I and Nam, HG and Zare, RN}, title = {Abiotic synthesis of purine and pyrimidine ribonucleosides in aqueous microdroplets.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {36-40}, pmid = {29255025}, issn = {1091-6490}, mesh = {Purine Nucleosides/*chemical synthesis/chemistry ; Pyrimidine Nucleosides/*chemical synthesis/chemistry ; }, abstract = {Aqueous microdroplets (<1.3 µm in diameter on average) containing 15 mM d-ribose, 15 mM phosphoric acid, and 5 mM of a nucleobase (uracil, adenine, cytosine, or hypoxanthine) are electrosprayed from a capillary at +5 kV into a mass spectrometer at room temperature and 1 atm pressure with 3 mM divalent magnesium ion (Mg2+) as a catalyst. Mass spectra show the formation of ribonucleosides that comprise a four-letter alphabet of RNA with a yield of 2.5% of uridine (U), 2.5% of adenosine (A), 0.7% of cytidine (C), and 1.7% of inosine (I) during the flight time of ∼50 µs. In the case of uridine, no catalyst is required. An aqueous solution containing guanine cannot be generated under the same conditions given the extreme insolubility of guanine in water. However, inosine can base pair with cytidine and thus substitute for guanosine. Thus, a full set of ribonucleosides to generate the purine-pyrimidine base pairs A-U and I-C are spontaneously generated in aqueous microdroplets under similar mild conditions.}, } @article {pmid29255024, year = {2018}, author = {Singh, N and Schwartzentruber, T}, title = {Nonequilibrium internal energy distributions during dissociation.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {47-52}, pmid = {29255024}, issn = {1091-6490}, abstract = {In this work, we propose a model for nonequilibrium vibrational and rotational energy distributions in nitrogen using surprisal analysis. The model is constructed by using data from direct molecular simulations (DMSs) of rapidly heated nitrogen gas using an ab initio potential energy surface (PES). The surprisal-based model is able to capture the overpopulation of high internal energy levels during the excitation phase and also the depletion of high internal energy levels during the quasi-steady-state (QSS) dissociation phase. Due to strong coupling between internal energy and dissociation chemistry, such non-Boltzmann effects can influence the overall dissociation rate in the gas. Conditions representative of the flow behind strong shockwaves, relevant to hypersonic flight, are analyzed. The surprisal-based model captures important molecular-level nonequilibrium physics, yet the simple functional form leads to a continuum-level expression that now accounts for the underlying energy distributions and their coupling to dissociation.}, } @article {pmid29255023, year = {2018}, author = {Long, CP and Gonzalez, JE and Feist, AM and Palsson, BO and Antoniewicz, MR}, title = {Dissecting the genetic and metabolic mechanisms of adaptation to the knockout of a major metabolic enzyme in Escherichia coli.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {222-227}, pmid = {29255023}, issn = {1091-6490}, mesh = {*Adaptation, Physiological ; *Directed Molecular Evolution ; *Energy Metabolism ; Escherichia coli/genetics/*metabolism ; Escherichia coli Proteins/*genetics/metabolism ; *Gene Knockdown Techniques ; Glucose-6-Phosphate Isomerase/*genetics ; NADP Transhydrogenase, B-Specific/genetics/metabolism ; NADP Transhydrogenases/genetics/metabolism ; }, abstract = {Unraveling the mechanisms of microbial adaptive evolution following genetic or environmental challenges is of fundamental interest in biological science and engineering. When the challenge is the loss of a metabolic enzyme, adaptive responses can also shed significant insight into metabolic robustness, regulation, and areas of kinetic limitation. In this study, whole-genome sequencing and high-resolution 13C-metabolic flux analysis were performed on 10 adaptively evolved pgi knockouts of Escherichia coliPgi catalyzes the first reaction in glycolysis, and its loss results in major physiological and carbon catabolism pathway changes, including an 80% reduction in growth rate. Following adaptive laboratory evolution (ALE), the knockouts increase their growth rate by up to 3.6-fold. Through combined genomic-fluxomic analysis, we characterized the mutations and resulting metabolic fluxes that enabled this fitness recovery. Large increases in pyridine cofactor transhydrogenase flux, correcting imbalanced production of NADPH and NADH, were enabled by direct mutations to the transhydrogenase genes sthA and pntAB The phosphotransferase system component crr was also found to be frequently mutated, which corresponded to elevated flux from pyruvate to phosphoenolpyruvate. The overall energy metabolism was found to be strikingly robust, and what have been previously described as latently activated Entner-Doudoroff and glyoxylate shunt pathways are shown here to represent no real increases in absolute flux relative to the wild type. These results indicate that the dominant mechanism of adaptation was to relieve the rate-limiting steps in cofactor metabolism and substrate uptake and to modulate global transcriptional regulation from stress response to catabolism.}, } @article {pmid29255022, year = {2018}, author = {Gautam, US and Foreman, TW and Bucsan, AN and Veatch, AV and Alvarez, X and Adekambi, T and Golden, NA and Gentry, KM and Doyle-Meyers, LA and Russell-Lodrigue, KE and Didier, PJ and Blanchard, JL and Kousoulas, KG and Lackner, AA and Kalman, D and Rengarajan, J and Khader, SA and Kaushal, D and Mehra, S}, title = {In vivo inhibition of tryptophan catabolism reorganizes the tuberculoma and augments immune-mediated control of Mycobacterium tuberculosis.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E62-E71}, pmid = {29255022}, issn = {1091-6490}, support = {R01 AI123780/AI/NIAID NIH HHS/United States ; UC6 AI058609/AI/NIAID NIH HHS/United States ; R01 HL106790/HL/NHLBI NIH HHS/United States ; R01 AI111914/AI/NIAID NIH HHS/United States ; R21 AI128130/AI/NIAID NIH HHS/United States ; R01 AI123047/AI/NIAID NIH HHS/United States ; R21 AI127222/AI/NIAID NIH HHS/United States ; R01 AI111943/AI/NIAID NIH HHS/United States ; P51 OD011104/OD/NIH HHS/United States ; R21 AI127160/AI/NIAID NIH HHS/United States ; P30 GM110760/GM/NIGMS NIH HHS/United States ; R01 AI089323/AI/NIAID NIH HHS/United States ; R01 AI134240/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; CD4-Positive T-Lymphocytes/immunology ; Cell Proliferation ; Granuloma/immunology/pathology ; Indoleamine-Pyrrole 2,3,-Dioxygenase/*immunology ; Lung/*immunology/pathology ; Macaca mulatta ; Macrophages/immunology/pathology ; Mycobacterium tuberculosis/*immunology/pathogenicity ; Tryptophan/*immunology ; Tuberculoma/*immunology/pathology ; Tuberculosis, Pulmonary/*immunology/pathology ; }, abstract = {Mycobacterium tuberculosis continues to cause devastating levels of mortality due to tuberculosis (TB). The failure to control TB stems from an incomplete understanding of the highly specialized strategies that M. tuberculosis utilizes to modulate host immunity and thereby persist in host lungs. Here, we show that M. tuberculosis induced the expression of indoleamine 2,3-dioxygenase (IDO), an enzyme involved in tryptophan catabolism, in macrophages and in the lungs of animals (mice and macaque) with active disease. In a macaque model of inhalation TB, suppression of IDO activity reduced bacterial burden, pathology, and clinical signs of TB disease, leading to increased host survival. This increased protection was accompanied by increased lung T cell proliferation, induction of inducible bronchus-associated lymphoid tissue and correlates of bacterial killing, reduced checkpoint signaling, and the relocation of effector T cells to the center of the granulomata. The enhanced killing of M. tuberculosis in macrophages in vivo by CD4+ T cells was also replicated in vitro, in cocultures of macaque macrophages and CD4+ T cells. Collectively, these results suggest that there exists a potential for using IDO inhibition as an effective and clinically relevant host-directed therapy for TB.}, } @article {pmid29255021, year = {2018}, author = {Lai, HH and Grefe, SE and Paschen, S and Si, Q}, title = {Weyl-Kondo semimetal in heavy-fermion systems.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {93-97}, pmid = {29255021}, issn = {1091-6490}, abstract = {Insulating states can be topologically nontrivial, a well-established notion that is exemplified by the quantum Hall effect and topological insulators. By contrast, topological metals have not been experimentally evidenced until recently. In systems with strong correlations, they have yet to be identified. Heavy-fermion semimetals are a prototype of strongly correlated systems and, given their strong spin-orbit coupling, present a natural setting to make progress. Here, we advance a Weyl-Kondo semimetal phase in a periodic Anderson model on a noncentrosymmetric lattice. The quasiparticles near the Weyl nodes develop out of the Kondo effect, as do the surface states that feature Fermi arcs. We determine the key signatures of this phase, which are realized in the heavy-fermion semimetal Ce3Bi4Pd3 Our findings provide the much-needed theoretical foundation for the experimental search of topological metals with strong correlations and open up an avenue for systematic studies of such quantum phases that naturally entangle multiple degrees of freedom.}, } @article {pmid29255020, year = {2018}, author = {Janion-Scheepers, C and Phillips, L and Sgrò, CM and Duffy, GA and Hallas, R and Chown, SL}, title = {Basal resistance enhances warming tolerance of alien over indigenous species across latitude.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {145-150}, pmid = {29255020}, issn = {1091-6490}, mesh = {Acclimatization/*physiology ; Australia ; *Ecosystem ; *Global Warming ; *Introduced Species ; *Models, Biological ; *Plant Physiological Phenomena ; *Plants ; }, abstract = {Soil systems are being increasingly exposed to the interactive effects of biological invasions and climate change, with rising temperatures expected to benefit alien over indigenous species. We assessed this expectation for an important soil-dwelling group, the springtails, by determining whether alien species show broader thermal tolerance limits and greater tolerance to climate warming than their indigenous counterparts. We found that, from the tropics to the sub-Antarctic, alien species have the broadest thermal tolerances and greatest tolerance to environmental warming. Both groups of species show little phenotypic plasticity or potential for evolutionary change in tolerance to high temperature. These trait differences between alien and indigenous species suggest that biological invasions will exacerbate the impacts of climate change on soil systems, with profound implications for terrestrial ecosystem functioning.}, } @article {pmid29255019, year = {2018}, author = {Lappe, RR and Baier, JW and Boehlein, SK and Huffman, R and Lin, Q and Wattebled, F and Settles, AM and Hannah, LC and Borisjuk, L and Rolletschek, H and Stewart, JD and Scott, MP and Hennen-Bierwagen, TA and Myers, AM}, title = {Functions of maize genes encoding pyruvate phosphate dikinase in developing endosperm.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E24-E33}, pmid = {29255019}, issn = {1091-6490}, mesh = {Endosperm/*enzymology/genetics ; Energy Metabolism/*physiology ; Mutation ; Plant Proteins/genetics/*metabolism ; Pyruvate, Orthophosphate Dikinase/genetics/*metabolism ; Starch/biosynthesis/genetics ; Transcription Factors/genetics/metabolism ; Zea mays/*enzymology/genetics ; }, abstract = {Maize opaque2 (o2) mutations are beneficial for endosperm nutritional quality but cause negative pleiotropic effects for reasons that are not fully understood. Direct targets of the bZIP transcriptional regulator encoded by o2 include pdk1 and pdk2 that specify pyruvate phosphate dikinase (PPDK). This enzyme reversibly converts AMP, pyrophosphate, and phosphoenolpyruvate to ATP, orthophosphate, and pyruvate and provides diverse functions in plants. This study addressed PPDK function in maize starchy endosperm where it is highly abundant during grain fill. pdk1 and pdk2 were inactivated individually by transposon insertions, and both genes were simultaneously targeted by endosperm-specific RNAi. pdk2 accounts for the large majority of endosperm PPDK, whereas pdk1 specifies the abundant mesophyll form. The pdk1- mutation is seedling-lethal, indicating that C4 photosynthesis is essential in maize. RNAi expression in transgenic endosperm eliminated detectable PPDK protein and enzyme activity. Transgenic kernels weighed the same on average as nontransgenic siblings, with normal endosperm starch and total N contents, indicating that PPDK is not required for net storage compound synthesis. An opaque phenotype resulted from complete PPDK knockout, including loss of vitreous endosperm character similar to the phenotype conditioned by o2-. Concentrations of multiple glycolytic intermediates were elevated in transgenic endosperm, energy charge was altered, and starch granules were more numerous but smaller on average than normal. The data indicate that PPDK modulates endosperm metabolism, potentially through reversible adjustments to energy charge, and reveal that o2- mutations can affect the opaque phenotype through regulation of PPDK in addition to their previously demonstrated effects on storage protein gene expression.}, } @article {pmid29255018, year = {2018}, author = {Mankowski, MC and Kinchen, VJ and Wasilewski, LN and Flyak, AI and Ray, SC and Crowe, JE and Bailey, JR}, title = {Synergistic anti-HCV broadly neutralizing human monoclonal antibodies with independent mechanisms.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E82-E91}, pmid = {29255018}, issn = {1091-6490}, support = {K08 AI102761/AI/NIAID NIH HHS/United States ; P30 AI094189/AI/NIAID NIH HHS/United States ; R01 AI127469/AI/NIAID NIH HHS/United States ; U19 AI088791/AI/NIAID NIH HHS/United States ; }, mesh = {Antibodies, Monoclonal/*immunology ; Antibodies, Neutralizing/*immunology ; HEK293 Cells ; Hepacivirus/*immunology ; Hepatitis Antibodies/*immunology ; Hepatitis C/*immunology/prevention & control ; Humans ; Viral Hepatitis Vaccines/immunology ; }, abstract = {There is an urgent need for a vaccine to combat the hepatitis C virus (HCV) pandemic, and induction of broadly neutralizing monoclonal antibodies (bNAbs) against HCV is a major goal of vaccine development. Even within HCV genotype 1, no single bNAb effectively neutralizes all viral strains, so induction of multiple neutralizing monoclonal antibodies (NAbs) targeting distinct epitopes may be necessary for protective immunity. Therefore, identification of optimal NAb combinations and characterization of NAb interactions can guide vaccine development. We analyzed neutralization profiles of 12 human NAbs across diverse HCV strains, assigning the NAbs to two functionally distinct clusters. We then measured neutralizing breadth of 35 NAb combinations against genotype 1 isolates, with each combination including one NAb from each neutralization cluster. Many NAbs displayed complementary neutralizing breadth, forming combinations with greater neutralization across diverse strains than any individual bNAb. Remarkably, one of the most broadly neutralizing combinations of two NAbs, designated HEPC74/HEPC98, also displayed enhanced potency, with interactions matching the Bliss independence model, suggesting that these NAbs inhibit HCV infection through independent mechanisms. Subsequent experiments showed that HEPC74 primarily blocks HCV envelope protein binding to CD81, while HEPC98 primarily blocks binding to scavenger receptor B1 and heparan sulfate. Together, these data identify a critical vulnerability resulting from the reliance of HCV on multiple cell surface receptors, suggesting that vaccine induction of multiple NAbs with distinct neutralization profiles is likely to enhance the breadth and potency of the humoral immune response against HCV.}, } @article {pmid29255017, year = {2018}, author = {Darby, RR and Horn, A and Cushman, F and Fox, MD}, title = {Lesion network localization of criminal behavior.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {601-606}, pmid = {29255017}, issn = {1091-6490}, support = {K23 NS083741/NS/NINDS NIH HHS/United States ; }, mesh = {Adult ; Brain/diagnostic imaging/pathology/*physiology ; Brain Mapping ; Cohort Studies ; *Criminal Behavior ; Criminals/psychology ; Female ; Humans ; Male ; Young Adult ; }, abstract = {Following brain lesions, previously normal patients sometimes exhibit criminal behavior. Although rare, these cases can lend unique insight into the neurobiological substrate of criminality. Here we present a systematic mapping of lesions with known temporal association to criminal behavior, identifying 17 lesion cases. The lesion sites were spatially heterogeneous, including the medial prefrontal cortex, orbitofrontal cortex, and different locations within the bilateral temporal lobes. No single brain region was damaged in all cases. Because lesion-induced symptoms can come from sites connected to the lesion location and not just the lesion location itself, we also identified brain regions functionally connected to each lesion location. This technique, termed lesion network mapping, has recently identified regions involved in symptom generation across a variety of lesion-induced disorders. All lesions were functionally connected to the same network of brain regions. This criminality-associated connectivity pattern was unique compared with lesions causing four other neuropsychiatric syndromes. This network includes regions involved in morality, value-based decision making, and theory of mind, but not regions involved in cognitive control or empathy. Finally, we replicated our results in a separate cohort of 23 cases in which a temporal relationship between brain lesions and criminal behavior was implied but not definitive. Our results suggest that lesions in criminals occur in different brain locations but localize to a unique resting state network, providing insight into the neurobiology of criminal behavior.}, } @article {pmid29255016, year = {2018}, author = {McDonald, GC and Pizzari, T}, title = {Structure of sexual networks determines the operation of sexual selection.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E53-E61}, pmid = {29255016}, issn = {1091-6490}, support = {//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; *Biological Evolution ; Female ; Male ; Mating Preference, Animal/*physiology ; *Models, Biological ; Selection, Genetic/*physiology ; }, abstract = {Sexual selection is a fundamental evolutionary process but remains debated, particularly in the complexity of polyandrous populations where females mate with multiple males. This lack of resolution is partly because studies have largely ignored the structure of the sexual network, that is, the pattern of mate sharing. Here, we quantify what we call mating assortment with network analysis to specify explicitly the indirect as well as direct relationships between partners. We first review empirical studies, showing that mating assortment varies considerably in nature, due largely to basic properties of the sexual network (size and density) and partly to nonrandom patterns of mate sharing. We then use simulations to show how variation in mating assortment interacts with population-level polyandry to determine the strength of sexual selection on males. Controlling for average polyandry, positive mating assortment, arising when more polygynous males tend to mate with more polyandrous females, drastically decreases the intensity of precopulatory sexual selection on male mating success (Bateman gradient) and the covariance between male mating success and postcopulatory paternity share. Average polyandry independently weakened some measures of sexual selection and crucially also impacted sexual selection indirectly by constraining mating assortment through the saturation of the mating network. Mating assortment therefore represents a key-albeit overlooked-modulator of the strength of sexual selection. Our results show that jointly considering sexual network structure and average polyandry more precisely describes the strength of sexual selection.}, } @article {pmid29255015, year = {2018}, author = {De Castro, C and Klose, T and Speciale, I and Lanzetta, R and Molinaro, A and Van Etten, JL and Rossmann, MG}, title = {Structure of the chlorovirus PBCV-1 major capsid glycoprotein determined by combining crystallographic and carbohydrate molecular modeling approaches.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E44-E52}, pmid = {29255015}, issn = {1091-6490}, support = {P20 RR015635/RR/NCRR NIH HHS/United States ; R01 AI011219/AI/NIAID NIH HHS/United States ; R37 AI011219/AI/NIAID NIH HHS/United States ; }, mesh = {Capsid Proteins/*chemistry ; Carbohydrate Conformation ; Crystallography, X-Ray ; Glycoproteins/*chemistry ; Glycosylation ; *Models, Molecular ; Phycodnaviridae/*chemistry ; }, abstract = {The glycans of the major capsid protein (Vp54) of Paramecium bursaria chlorella virus (PBCV-1) were recently described and found to be unusual. This prompted a reexamination of the previously reported Vp54 X-ray structure. A detailed description of the complete glycoprotein was achieved by combining crystallographic data with molecular modeling. The crystallographic data identified most of the monosaccharides located close to the protein backbone, but failed to detect those further from the glycosylation sites. Molecular modeling complemented this model by adding the missing monosaccharides and examined the conformational preference of the whole molecule, alone or within the crystallographic environment. Thus, combining X-ray crystallography with carbohydrate molecular modeling resulted in determining the complete glycosylated structure of a glycoprotein. In this case, it is the chlorovirus PBCV-1 major capsid protein.}, } @article {pmid29255014, year = {2018}, author = {Bergauer, K and Fernandez-Guerra, A and Garcia, JAL and Sprenger, RR and Stepanauskas, R and Pachiadaki, MG and Jensen, ON and Herndl, GJ}, title = {Organic matter processing by microbial communities throughout the Atlantic water column as revealed by metaproteomics.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E400-E408}, pmid = {29255014}, issn = {1091-6490}, support = {268595//European Research Council/International ; }, mesh = {Archaea/genetics/*metabolism ; Archaeal Proteins/*metabolism ; Atlantic Ocean ; Bacteria/genetics/*metabolism ; Bacterial Proteins/*metabolism ; Biodiversity ; Genome, Archaeal ; Genome, Bacterial ; Metagenomics ; Proteomics/*methods ; Seawater ; *Water Microbiology ; }, abstract = {The phylogenetic composition of the heterotrophic microbial community is depth stratified in the oceanic water column down to abyssopelagic layers. In the layers below the euphotic zone, it has been suggested that heterotrophic microbes rely largely on solubilized particulate organic matter as a carbon and energy source rather than on dissolved organic matter. To decipher whether changes in the phylogenetic composition with depth are reflected in changes in the bacterial and archaeal transporter proteins, we generated an extensive metaproteomic and metagenomic dataset of microbial communities collected from 100- to 5,000-m depth in the Atlantic Ocean. By identifying which compounds of the organic matter pool are absorbed, transported, and incorporated into microbial cells, intriguing insights into organic matter transformation in the deep ocean emerged. On average, solute transporters accounted for 23% of identified protein sequences in the lower euphotic and ∼39% in the bathypelagic layer, indicating the central role of heterotrophy in the dark ocean. In the bathypelagic layer, substrate affinities of expressed transporters suggest that, in addition to amino acids, peptides and carbohydrates, carboxylic acids and compatible solutes may be essential substrates for the microbial community. Key players with highest expression of solute transporters were Alphaproteobacteria, Gammaproteobacteria, and Deltaproteobacteria, accounting for 40%, 11%, and 10%, respectively, of relative protein abundances. The in situ expression of solute transporters indicates that the heterotrophic prokaryotic community is geared toward the utilization of similar organic compounds throughout the water column, with yet higher abundances of transporters targeting aromatic compounds in the bathypelagic realm.}, } @article {pmid29255013, year = {2018}, author = {Bradshaw, WE and Burkhart, J and Colbourne, JK and Borowczak, R and Lopez, J and Denlinger, DL and Reynolds, JA and Pfrender, ME and Holzapfel, CM}, title = {Evolutionary transition from blood feeding to obligate nonbiting in a mosquito.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {5}, pages = {1009-1014}, pmid = {29255013}, issn = {1091-6490}, support = {T15 LM007088/LM/NLM NIH HHS/United States ; }, mesh = {Animals ; Blood ; Blood-Borne Pathogens ; Culicidae/*genetics/*pathogenicity/physiology ; *Evolution, Molecular ; *Feeding Behavior/physiology ; Female ; Gene Expression ; Genes, Insect ; Genetics, Population ; Humans ; Insect Bites and Stings/parasitology ; Insect Proteins/genetics ; Metabolic Networks and Pathways/genetics ; Models, Biological ; Mosquito Vectors/genetics/pathogenicity/physiology ; Rats ; Rats, Inbred SHR ; }, abstract = {The spread of blood-borne pathogens by mosquitoes relies on their taking a blood meal; if there is no bite, there is no disease transmission. Although many species of mosquitoes never take a blood meal, identifying genes that distinguish blood feeding from obligate nonbiting is hampered by the fact that these different lifestyles occur in separate, genetically incompatible species. There is, however, one unique extant species with populations that share a common genetic background but blood feed in one region and are obligate nonbiters in the rest of their range: Wyeomyia smithii Contemporary blood-feeding and obligate nonbiting populations represent end points of divergence between fully interfertile southern and northern populations. This divergence has undoubtedly resulted in genetic changes that are unrelated to blood feeding, and the challenge is to winnow out the unrelated genetic factors to identify those related specifically to the evolutionary transition from blood feeding to obligate nonbiting. Herein, we determine differential gene expression resulting from directional selection on blood feeding within a polymorphic population to isolate genetic differences between blood feeding and obligate nonbiting. We show that the evolution of nonbiting has resulted in a greatly reduced metabolic investment compared with biting populations, a greater reliance on opportunistic metabolic pathways, and greater reliance on visual rather than olfactory sensory input. W. smithii provides a unique starting point to determine if there are universal nonbiting genes in mosquitoes that could be manipulated as a means to control vector-borne disease.}, } @article {pmid29254983, year = {2018}, author = {Sztein, MB}, title = {Is a Human CD8 T-Cell Vaccine Possible, and if So, What Would It Take? CD8 T-Cell-Mediated Protective Immunity and Vaccination against Enteric Bacteria.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a029546}, pmid = {29254983}, issn = {1943-0264}, support = {R01 AI036525/AI/NIAID NIH HHS/United States ; U19 AI082655/AI/NIAID NIH HHS/United States ; U19 AI109776/AI/NIAID NIH HHS/United States ; }, abstract = {Although induction of CD8+ responses is widely accepted as critical in clearing viral infections and necessary for effective vaccines against viruses, much less is known regarding the role of these cells in bacterial and other infections, particularly those that enter the host via the gastrointestinal tract. In this commentary, I discuss the likelihood that CD8+ responses are also important in protection from intestinal Gram-negative bacteria, as well as the many factors that should be taken into consideration during the development of vaccines, based on eliciting long-term protection predominantly mediated by CD8+ responses against these organisms.}, } @article {pmid29254982, year = {2018}, author = {Beura, LK and Jameson, SC and Masopust, D}, title = {Is a Human CD8 T-Cell Vaccine Possible, and if So, What Would It Take? CD8 T-Cell Vaccines: To B or Not to B?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a028910}, pmid = {29254982}, issn = {1943-0264}, abstract = {Although CD8 T-cell vaccines do not have the record of success of humoral-mediated vaccines, they do not receive the same degree of effort. Many diseases, including malaria, tuberculosis, and acquired immune deficiency syndrome (AIDS) have not yielded to vaccines, and intrinsic barriers may impede approaches limited solely to generating antibodies. Moreover, population growth and modernization are driving an increased pace of new emerging global health threats (human immunodeficiency virus [HIV] is a recent example), which will create unpredictable challenges for vaccinologists. Vaccine-elicited CD8 T cells may contribute to protective modalities, although their development will require a more thorough understanding of CD8 T-cell biology, practices for manufacturing and delivering CD8 T-cell-eliciting vectors that have acceptable safety profiles, and, ultimately, the political will and faith of those that make vaccine research funding decisions.}, } @article {pmid29254981, year = {2018}, author = {Kissick, HT}, title = {Is It Possible to Develop Cancer Vaccines to Neoantigens, What Are the Major Challenges, and How Can These Be Overcome? Neoantigens as Vaccine Targets for Cancer.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a033704}, pmid = {29254981}, issn = {1943-0264}, abstract = {Recent work by several groups has undoubtedly shown that we can produce cancer vaccines targeting neoantigens. However, each vaccine is essentially a single-use, patient-specific product, making this approach resource-intensive. For this reason, it is important to ask whether this approach will be any more successful than what has been attempted during the last 30 years using vaccines targeting self-epitopes. Here, we discuss what might be expected from neoantigen vaccines based on our experience in chronic viral infections, and how this new approach may be applied to cancer immunotherapy.}, } @article {pmid29254980, year = {2018}, author = {Finn, OJ and Rammensee, HG}, title = {Is It Possible to Develop Cancer Vaccines to Neoantigens, What Are the Major Challenges, and How Can These Be Overcome? Neoantigens: Nothing New in Spite of the Name.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a028829}, pmid = {29254980}, issn = {1943-0264}, abstract = {The term "neoantigen," as applied to molecules newly expressed on tumor cells, has a long history. The groundbreaking discovery of a cancer causing virus in chickens by Rous over 100 years ago, followed by discoveries of other tumor-causing viruses in animals, suggested a viral etiology of human cancers. The search for other oncogenic viruses in the 1960s and 1970s resulted in the discoveries of Epstein-Barr virus (EBV), hepatitis B virus (HBV), and human papilloma virus (HPV), and continues until the present time. Contemporaneously, the budding field of immunology was posing the question can the immune system of animals or humans recognize a tumor that develops from one's own tissues and what types of antigens would distinguish the tumor from normal cells. Molecules encoded by oncogenic viruses provided the most logical candidates and evidence was quickly gathered for both humoral and cellular recognition of viral antigens, referred to as neoantigens. Often, however, serologic responses to virus-bearing tumors revealed neoantigens unrelated to viral proteins and expressed on multiple tumor types, foreshadowing later findings of multiple changes in other genes in tumor cells creating nonviral neoantigens.}, } @article {pmid29254979, year = {2018}, author = {Sun, JC and Lanier, LL}, title = {Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? NK Cell Memory and Immunization Strategies against Infectious Diseases and Cancer.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, pmid = {29254979}, issn = {1943-0264}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 AI068129/AI/NIAID NIH HHS/United States ; R01 AI100874/AI/NIAID NIH HHS/United States ; }, abstract = {Immunological memory is an evolutionary adaptation of the vertebrate immune system that protects the host from repeated pathogen infection. T and B cells possess the specificity and longevity required to generate immune memory, whereas natural killer (NK) cells make up a component of the immune system that was not thought to possess these features. However, much evidence from the last decade has challenged this dogma. The investigators were asked to address the following questions: Is there NK cell memory? And can NK cell memory be harnessed for vaccination? Thus, this article explores the recent literature showing immune memory in NK cells. Along with highlighting these studies, we speculate how NK cell memory can be harnessed in immunization strategies against infectious diseases and cancer.}, } @article {pmid29254978, year = {2018}, author = {Neely, HR and Mazo, IB and Gerlach, C and von Andrian, UH}, title = {Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Natural Killer Cells in Vaccination.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a029488}, pmid = {29254978}, issn = {1943-0264}, abstract = {Natural killer (NK) cells have historically been considered to be a part of the innate immune system, exerting a rapid response against pathogens and tumors in an antigen (Ag)-independent manner. However, over the past decade, evidence has accumulated suggesting that at least some NK cells display certain characteristics of adaptive immune cells. Indeed, NK cells can learn and remember encounters with a variety of Ags, including chemical haptens and viruses. Upon rechallenge, memory NK cells mount potent recall responses selectively to those Ags. This phenomenon, traditionally termed "immunological memory," has been reported in mice, nonhuman primates, and even humans and appears to be concentrated in discrete NK cell subsets. Because immunological memory protects against recurrent infections and is the central goal of active vaccination, it is crucial to define the mechanisms and consequences of NK cell memory. Here, we summarize the different kinds of memory responses that have been attributed to specific NK cell subsets and discuss the possibility to harness NK cell memory for vaccination purposes.}, } @article {pmid29254977, year = {2018}, author = {McMichael, AJ}, title = {Is a Human CD8 T-Cell Vaccine Possible, and if So, What Would It Take? Could a CD8+ T-Cell Vaccine Prevent Persistent HIV Infection?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, pmid = {29254977}, issn = {1943-0264}, support = {MR/K012037/1//Medical Research Council/United Kingdom ; UM1 AI100645/AI/NIAID NIH HHS/United States ; Z01 AI000645/AI/NIAID NIH HHS/United States ; }, abstract = {Vaccines that stimulate CD8+ T cells could clear early virus infection or control ongoing infection and prevent disease. This could be valuable to combat human immunodeficiency virus type 1 (HIV-1) where it has not yet been possible to generate broadly reacting neutralizing antibodies with a vaccine. However, HIV-1 vaccines aimed at stimulating CD8+ T cells have had no success. In contrast, a cytomegalovirus vectored simian immunodeficiency virus (SIV) vaccine enabled clearance of early SIV infection. This may open the door to the design of an effective HIV vaccine.}, } @article {pmid29254976, year = {2018}, author = {Cooper, MA and Fehniger, TA and Colonna, M}, title = {Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Vaccination Strategies Based on NK Cell and ILC Memory.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a029512}, pmid = {29254976}, issn = {1943-0264}, support = {R01 CA205239/CA/NCI NIH HHS/United States ; }, abstract = {Studies over the last decade have decisively shown that innate immune natural killer (NK) cells exhibit enhanced long-lasting functional responses following a single activation event. With the increased recognition of memory and memory-like properties of NK cells, questions have arisen with regard to their ability to effectively mediate vaccination responses in humans. Moreover, recently discovered innate lymphoid cells (ILCs) could also potentially exhibit memory-like functions. Here, we review different forms of NK cell memory, and speculate about the ability of these cells and ILCs to meaningfully contribute to vaccination responses.}, } @article {pmid29254975, year = {2018}, author = {Biron, CA and Altfeld, M}, title = {Is There Natural Killer Cell Memory and Can It Be Harnessed by Vaccination? Can Natural Killer and CD8 T Cells Switch Jobs?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a029892}, pmid = {29254975}, issn = {1943-0264}, abstract = {Natural killer (NK) cells are components of innate immunity mediating defense at early times after viral infections. Their cytokine production and cell-mediated cytotoxicity functions overlap those of CD8 T cells elicited later during primary adaptive immune responses, but the populations are distinguished by their basal states and activating receptors as well as the kinetics of their responses. Demonstration of long-lived NK cells has led to speculation on the potential for inducing these to contribute to immunological memory. Conversely, activated CD8 T cells can acquire responses to innate cytokines and, as a result, have the potential to contribute to innate immunity. These observations beg the question: what is required to be a player in innate and adaptive immunity?}, } @article {pmid29254974, year = {2018}, author = {Schoenberger, SP}, title = {Is It Possible to Develop Cancer Vaccines to Neoantigens, What Are the Major Challenges, and How Can These Be Overcome? Targeting the Right Antigens in the Right Patients.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a028837}, pmid = {29254974}, issn = {1943-0264}, abstract = {Recent advances in genomic sequencing and bioinformatics have empowered a revolution in immuno-oncology that has led to numerous unambiguous demonstrations of spontaneous and therapy-induced T-cell responses in patients against a subset of immunogenic tumor-specific somatic mutations known as neoantigens. These findings raise the exciting possibility that patients could be therapeutically treated with personalized vaccines against the mutations expressed by their own tumor. A central challenge for the broader clinical application of this approach will be to define the best antigens to target, to determine the subset of patients most likely to derive significant clinical benefit, and, finally, to discover both the best method of vaccine delivery and the optimal time in the disease course to do so. A growing number of translational immunologists believe that these challenges can be overcome and this perspective will discuss strategies to achieve this.}, } @article {pmid29254973, year = {2018}, author = {Edwards, D and Kenrick, P and Dolan, L}, title = {Dedication: Nigel Trewin (1944-2017).}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, doi = {10.1098/rstb.2017.0365}, pmid = {29254973}, issn = {1471-2970}, } @article {pmid29254972, year = {2018}, author = {Raven, JA and Giordano, M}, title = {Correction to 'Acquisition and metabolism of carbon in the Ochrophyta other than diatoms'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, doi = {10.1098/rstb.2017.0363}, pmid = {29254972}, issn = {1471-2970}, } @article {pmid29254971, year = {2018}, author = {Stapley, J and Feulner, PGD and Johnston, SE and Santure, AW and Smadja, CM}, title = {Correction to 'Variation in recombination frequency and distribution across eukaryotes: patterns and processes'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, doi = {10.1098/rstb.2017.0360}, pmid = {29254971}, issn = {1471-2970}, } @article {pmid29254970, year = {2018}, author = {Kenrick, P}, title = {Changing expressions: a hypothesis for the origin of the vascular plant life cycle.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254970}, issn = {1471-2970}, mesh = {*Biological Evolution ; Ecosystem ; Embryophyta/genetics/*physiology ; Gene Expression ; *Life History Traits ; Reproduction ; Scotland ; }, abstract = {Plant life cycles underwent fundamental changes during the initial colonization of the land in the Early Palaeozoic, shaping the direction of evolution. Fossils reveal unanticipated diversity, including new variants of meiotic cell division and leafless gametophytes with mycorrhizal-like symbioses, rhizoids, vascular tissues and stomata. Exceptional fossils from the 407-Ma Rhynie chert (Scotland) play a key role in unlocking this diversity. These fossils are reviewed against progress in our understanding of the plant tree of life and recent advances in developmental genetics. Combining data from different sources sheds light on a switch in life cycle that gave rise to the vascular plants. One crucial step was the establishment of a free-living sporophyte from one that was an obligate matrotroph borne on the gametophyte. It is proposed that this difficult evolutionary transition was achieved through expansion of gene expression primarily from the gametophyte to the sporophyte, establishing a now extinct life cycle variant that was more isomorphic than heteromorphic. These changes also linked for the first time in one developmental system rhizoids, vascular tissues and stomata, putting in place the critical components that regulate transpiration and forming a physiological platform of primary importance to the diversification of vascular plants.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254969, year = {2018}, author = {Honegger, R and Edwards, D and Axe, L and Strullu-Derrien, C}, title = {Fertile Prototaxites taiti: a basal ascomycete with inoperculate, polysporous asci lacking croziers.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254969}, issn = {1471-2970}, mesh = {Ascomycota/*classification/cytology/physiology ; Fossils/*anatomy & histology ; Phylogeny ; Reproduction ; Scotland ; Wales ; }, abstract = {The affinities of Prototaxites have been debated ever since its fossils, some attaining tree-trunk proportions, were discovered in Canadian Lower Devonian rocks in 1859. Putative assignations include conifers, red and brown algae, liverworts and fungi (some lichenised). Detailed anatomical investigation led to the reconstruction of the type species, P. logani, as a giant sporophore (basidioma) of an agaricomycete (= holobasidiomycete), but evidence for its reproduction remained elusive. Tissues associated with P. taiti in the Rhynie chert plus charcoalified fragments from southern Britain are investigated here to describe the reproductive characters and hence affinities of Prototaxites Thin sections and peels (Pragian Rhynie chert, Aberdeenshire) were examined using light and confocal microscopy; Přídolí and Lochkovian charcoalified samples (Welsh Borderland) were liberated from the rock and examined with scanning electron microscopy. Prototaxites taiti possessed a superficial hymenium comprising an epihymenial layer, delicate septate paraphyses, inoperculate polysporic asci lacking croziers and a subhymenial layer composed predominantly of thin-walled hyphae and occasional larger hyphae. Prototaxites taiti combines features of extant Taphrinomycotina (Neolectomycetes lacking croziers) and Pezizomycotina (epihymenial layer secreted by paraphyses) but is not an ancestor of the latter. Brief consideration is given to its nutrition and potential position in the phylogeny of the Ascomycota.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254968, year = {2018}, author = {Hetherington, AJ and Dolan, L}, title = {Bilaterally symmetric axes with rhizoids composed the rooting structure of the common ancestor of vascular plants.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254968}, issn = {1471-2970}, mesh = {*Biological Evolution ; Embryophyta/*anatomy & histology/physiology ; Fossils/*anatomy & histology ; Phylogeny ; Plant Roots/*anatomy & histology/physiology ; Scotland ; }, abstract = {There are two general types of rooting systems in extant land plants: gametophyte rhizoids and sporophyte root axes. These structures carry out the rooting function in the free-living stage of almost all land plant gametophytes and sporophytes, respectively. Extant vascular plants develop a dominant, free-living sporophyte on which roots form, with the exception of a small number of taxa that have secondarily lost roots. However, fossil evidence indicates that early vascular plants did not develop sporophyte roots. We propose that the common ancestor of vascular plants developed a unique rooting system-rhizoidal sporophyte axes. Here we present a synthesis and reinterpretation of the rootless sporophytes of Horneophyton lignieri, Aglaophyton majus, Rhynia gwynne-vaughanii and Nothia aphylla preserved in the Rhynie chert. We show that the sporophyte rooting structures of all four plants comprised regions of plagiotropic (horizontal) axes that developed unicellular rhizoids on their underside. These regions of axes with rhizoids developed bilateral symmetry making them distinct from the other regions which were radially symmetrical. We hypothesize that rhizoidal sporophyte axes constituted the rooting structures in the common ancestor of vascular plants because the phylogenetic positions of these plants span the origin of the vascular lineage.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254967, year = {2018}, author = {Mills, BJW and Batterman, SA and Field, KJ}, title = {Nutrient acquisition by symbiotic fungi governs Palaeozoic climate transition.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254967}, issn = {1471-2970}, mesh = {Atmosphere ; *Biological Evolution ; Carbon Dioxide/metabolism ; *Ecosystem ; Embryophyta/*physiology ; Fossils ; Fungi/*physiology ; Models, Biological ; *Symbiosis ; }, abstract = {Fossil evidence from the Rhynie chert indicates that early land plants, which evolved in a high-CO2 atmosphere during the Palaeozoic Era, hosted diverse fungal symbionts. It is hypothesized that the rise of early non-vascular land plants, and the later evolution of roots and vasculature, drove the long-term shift towards a high-oxygen, low CO2 climate that eventually permitted the evolution of mammals and, ultimately, humans. However, very little is known about the productivity of the early terrestrial biosphere, which depended on the acquisition of the limiting nutrient phosphorus via fungal symbiosis. Recent laboratory experiments have shown that plant-fungal symbiotic function is specific to fungal identity, with carbon-for-phosphorus exchange being either enhanced or suppressed under superambient CO2 By incorporating these experimental findings into a biogeochemical model, we show that the differences in these symbiotic nutrient acquisition strategies could greatly alter the plant-driven changes to climate, allowing drawdown of CO2 to glacial levels, and altering the nature of the rise of oxygen. We conclude that an accurate depiction of plant-fungal symbiotic systems, informed by high-CO2 experiments, is key to resolving the question of how the first terrestrial ecosystems altered our planet.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254966, year = {2018}, author = {Strullu-Derrien, C and Spencer, ART and Goral, T and Dee, J and Honegger, R and Kenrick, P and Longcore, JE and Berbee, ML}, title = {New insights into the evolutionary history of Fungi from a 407 Ma Blastocladiomycota fossil showing a complex hyphal thallus.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254966}, issn = {1471-2970}, mesh = {Biological Evolution ; Blastocladiomycota/*classification/cytology/physiology ; Fossils/*anatomy & histology ; Hyphae/cytology/physiology ; Microscopy ; Microscopy, Confocal ; Phylogeny ; Scotland ; }, abstract = {Zoosporic fungi are key saprotrophs and parasites of plants, animals and other fungi, playing important roles in ecosystems. They comprise at least three phyla, of which two, Chytridiomycota and Blastocladiomycota, developed a range of thallus morphologies including branching hyphae. Here we describe Retesporangicus lyonii gen. et sp. nov., an exceptionally well preserved fossil, which is the earliest known to produce multiple sporangia on an expanded hyphal network. To better characterize the fungus we develop a new method to render surfaces from image stacks generated by confocal laser scanning microscopy. Here, the method helps to reveal thallus structure. Comparisons with cultures of living species and character state reconstructions analysed against recent molecular phylogenies of 24 modern zoosporic fungi indicate an affinity with Blastocladiomycota. We argue that in zoosporic fungi, kinds of filaments such as hyphae, rhizoids and rhizomycelium are developmentally similar structures adapted for varied functions including nutrient absorption and anchorage. The fossil is the earliest known type to develop hyphae which likely served as a saprotrophic adaptation to patchy resource availability. Evidence from the Rhynie chert provides our earliest insights into the biology of fungi and their roles in the environment. It demonstrates that zoosporic fungi were already diverse in 407 million-year-old terrestrial ecosystems.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254965, year = {2018}, author = {Krings, M and Harper, CJ and Taylor, EL}, title = {Fungi and fungal interactions in the Rhynie chert: a review of the evidence, with the description of Perexiflasca tayloriana gen. et sp. nov.†.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254965}, issn = {1471-2970}, mesh = {Chytridiomycota/classification/cytology/physiology ; Ecosystem ; Embryophyta/*microbiology ; *Fossils/anatomy & histology ; Fungi/*classification/cytology/*physiology ; Scotland ; }, abstract = {The Lower Devonian Rhynie chert is one of the most important rock deposits yielding comprehensive information on early continental plant, animal and microbial life. Fungi are especially abundant among the microbial remains, and include representatives of all major fungal lineages except Basidiomycota. This paper surveys the evidence assembled to date of fungal hyphae, mycelial cords and reproductive units (e.g. spores, sporangia, sporocarps), and presents examples of fungal associations and interactions with land plants, other fungi, algae, cyanobacteria and animals from the Rhynie chert. Moreover, a small, chytrid-like organism that occurs singly, in chain-like, linear arrangements, planar assemblages and three-dimensional aggregates of less than 10 to [Formula: see text] individuals in degrading land plant tissue in the Rhynie chert is formally described, and the name Perexiflasca tayloriana proposed for the organism. Perexiflasca tayloriana probably colonized senescent or atrophied plant parts and participated in the process of biological degradation. The fungal fossils described to date from the Rhynie chert constitute the largest body of structurally preserved evidence of fungi and fungal interactions from any rock deposit, and strongly suggest that fungi played important roles in the functioning of the Early Devonian Rhynie ecosystem.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254964, year = {2018}, author = {Abbott, GD and Fletcher, IW and Tardio, S and Hack, E}, title = {Exploring the geochemical distribution of organic carbon in early land plants: a novel approach.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254964}, issn = {1471-2970}, mesh = {Carbon/*analysis ; Embryophyta/*chemistry ; Fossils/*diagnostic imaging ; Organic Chemicals/analysis ; Paleontology/*methods ; Spectrometry, Mass, Secondary Ion/*methods ; }, abstract = {Terrestrialization depended on the evolution of biosynthetic pathways for biopolymers including lignin, cutin and suberin, which were concentrated in specific tissues, layers or organs such as the xylem, cuticle and roots on the submillimetre scale. However, it is often difficult, or even impossible especially for individual cells, to resolve the biomolecular composition of the different components of fossil plants on such a scale using the well-established coupled techniques of gas chromatography/mass spectrometry and liquid chromatography/mass spectrometry. Here, we report the application of techniques for surface analysis to investigate the composition of Rhynia gwynne-vaughanii X-ray photoelectron spectroscopy of two different spots (both 300 µm × 600 µm) confirmed the presence of carbon. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) revealed 'chemical maps' (imaging mode with 300 nm resolution) of aliphatic and aromatic carbon in the intact fossil that correlate with the vascular structures observed in high-resolution optical images. This study shows that imaging ToF-SIMS has value for determining the location of the molecular components of fossil embryophytes while retaining structural information that will help elucidate how terrestrialization shaped the early evolution of land plant cell wall biochemistry.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254963, year = {2018}, author = {Duckett, JG and Pressel, S}, title = {The evolution of the stomatal apparatus: intercellular spaces and sporophyte water relations in bryophytes-two ignored dimensions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254963}, issn = {1471-2970}, mesh = {*Biological Evolution ; Bryophyta/*physiology ; Extracellular Space/*physiology ; Plant Stomata/*physiology ; }, abstract = {Cryo-scanning electron microscopy shows that nascent intercellular spaces (ICSs) in bryophytes are liquid-filled, whereas these are gas-filled from the outset in tracheophytes except in the gametophytes of Lycopodiales. ICSs are absent in moss gametophytes and remain liquid-filled in hornwort gametophytes and in both generations in liverworts. Liquid is replaced by gas following stomatal opening in hornworts and is ubiquitous in moss sporophytes even in astomate taxa. New data on moss water relations and sporophyte weights indicate that the latter are homiohydric while X-ray microanalysis reveals an absence of potassium pumps in the stomatal apparatus. The distribution of ICSs in bryophytes is strongly indicative of very ancient multiple origins. Inherent in this scenario is either the dual or triple evolution of stomata. The absence, in mosses, of any relationship between increases in sporophyte biomass and stomata numbers and absences, suggests that CO2 entry through the stomata, possible only after fluid replacement by gas in the ICSs, makes but a minor contribution to sporophyte nutrition. Save for a single claim of active regulation of aperture dimensions in mosses, all other functional and structural data point to the sporophyte desiccation, leading to spore discharge, as the primeval role of the stomatal apparatus.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254962, year = {2018}, author = {Raven, JA}, title = {Evolution and palaeophysiology of the vascular system and other means of long-distance transport.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254962}, issn = {1471-2970}, mesh = {Biological Transport ; Embryophyta/*physiology ; *Fossils ; Paleontology ; Plant Vascular Bundle/*physiology ; Scotland ; }, abstract = {Photolithotrophic growth on land using atmospheric CO2 inevitably involves H2O vapour loss. Embryophytes greater than or equal to 100 mm tall are homoiohydric and endohydric with mass flow of aqueous solution through the xylem in tracheophytes. Structural details in Rhynie sporophytes enable modelling of the hydraulics of H2O supply to the transpiring surface, and the potential for gas exchange with the Devonian atmosphere. Xylem carrying H2O under tension involves programmed cell death, rigid cell walls and embolism repair; fossils provide little evidence on these functions other than the presence of lignin. The phenylalanine ammonia lyase essential for lignin synthesis came from horizontal gene transfer. Rhynie plants lack endodermes, limiting regulation of the supply of soil nutrients to shoots. The transfer of organic solutes from photosynthetic sites to growing and storage tissues involves mass flow through phloem in extant tracheophytes. Rhynie plants show little evidence of phloem; possible alternatives for transport of organic solutes are discussed. Extant examples of the arbuscular mycorrhizas found in Rhynie plants exchange soil-derived nutrients (especially P) for plant-derived organic matter, involving bidirectional mass flow along the hyphae. The aquatic cyanobacteria and the charalean Palaeonitella at Rhynie also have long-distance (relative to the size of the organism) transport.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254961, year = {2018}, author = {Harrison, CJ and Morris, JL}, title = {The origin and early evolution of vascular plant shoots and leaves.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254961}, issn = {1471-2970}, mesh = {*Biological Evolution ; Fossils/anatomy & histology ; Phylogeny ; Plant Leaves/anatomy & histology/genetics/growth & development ; Plant Shoots/anatomy & histology/genetics/growth & development ; *Tracheophyta/anatomy & histology/genetics/growth & development ; }, abstract = {The morphology of plant fossils from the Rhynie chert has generated longstanding questions about vascular plant shoot and leaf evolution, for instance, which morphologies were ancestral within land plants, when did vascular plants first arise and did leaves have multiple evolutionary origins? Recent advances combining insights from molecular phylogeny, palaeobotany and evo-devo research address these questions and suggest the sequence of morphological innovation during vascular plant shoot and leaf evolution. The evidence pinpoints testable developmental and genetic hypotheses relating to the origin of branching and indeterminate shoot architectures prior to the evolution of leaves, and demonstrates underestimation of polyphyly in the evolution of leaves from branching forms in 'telome theory' hypotheses of leaf evolution. This review discusses fossil, developmental and genetic evidence relating to the evolution of vascular plant shoots and leaves in a phylogenetic framework.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254960, year = {2018}, author = {Kerp, H}, title = {Organs and tissues of Rhynie chert plants.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254960}, issn = {1471-2970}, mesh = {*Biological Evolution ; Embryophyta/*anatomy & histology ; Fossils/*anatomy & histology ; Scotland ; }, abstract = {The Early Devonian Rhynie chert and the nearby Windyfield chert contain the oldest in situ preserved terrestrial ecosystem. Two of the seven species of anatomically preserved land plants had naked axes, one an axis with a more or less regular pattern of short-longitudinal ribs, two species had spiny axes and one species had small leaf-like appendages. All plants mainly consist of parenchymatous tissues. In some species, conducting elements comprise uniformly thickened thick-walled cells resembling hydroids of larger bryophytes, whereas others have real tracheids with annular and/or spiral secondary wall thickenings. True phloem has never been demonstrated but in all species the thick-walled water-conducting cells are encircled by a zone of thin-walled cells without intercellular spaces. The cortex is differentiated into two or three zones and forms the major part of the axes; in one species the cells of the middle cortex are sclerified. Some species have a hypodermis. In all species the epidermis is covered by a well-developed cuticle. Sporangia are known from all species. Sporangia are spindle-shaped, lobed or kidney-shaped and attached terminally or laterally with a short stalk. Gametophytes of four species have been described. Gametophytes are unisexual, isomorphic but much smaller than the sporophytes.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254959, year = {2018}, author = {Kofuji, R and Yagita, Y and Murata, T and Hasebe, M}, title = {Antheridial development in the moss Physcomitrella patens: implications for understanding stem cells in mosses.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254959}, issn = {1471-2970}, mesh = {Biological Evolution ; Bryopsida/*growth & development ; Flowers/*growth & development ; *Gametogenesis, Plant ; Stem Cells/*cytology ; }, abstract = {Stem cells self-renew and produce precursor cells that differentiate to become specialized cell types. Land plants generate several types of stem cells that give rise to most organs of the plant body and whose characters determine the body organization. The moss Physcomitrella patens forms eight types of stem cells throughout its life cycle. Under gametangium-inducing conditions, multiple antheridium apical stem cells are formed at the tip of the gametophore and each antheridium apical stem cell divides to form an antheridium. We found that the gametophore apical stem cell, which typically forms leaf and stem tissues, changes to become a new type of stem cell, which we term the antheridium initial stem cell. This antheridium initial stem cell produces multiple antheridium apical stem cells, resulting in a cluster of antheridia at the tip of gametophore. This is the first report of a land plant stem cell directly producing another type of stem cell during normal development. Notably, the antheridium apical stem cells are distally produced from the antheridium initial stem cell, similar to the root cap stem cells of vascular plants, suggesting the use of similar molecular mechanisms and a possible evolutionary relationship.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254958, year = {2018}, author = {Dunlop, JA and Garwood, RJ}, title = {Terrestrial invertebrates in the Rhynie chert ecosystem.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254958}, issn = {1471-2970}, mesh = {Animals ; *Biological Evolution ; Ecosystem ; *Fossils ; Invertebrates/anatomy & histology/*classification/physiology ; Paleontology ; Scotland ; }, abstract = {The Early Devonian Rhynie and Windyfield cherts remain a key locality for understanding early life and ecology on land. They host the oldest unequivocal nematode worm (Nematoda), which may also offer the earliest evidence for herbivory via plant parasitism. The trigonotarbids (Arachnida: Trigonotarbida) preserve the oldest book lungs and were probably predators that practiced liquid feeding. The oldest mites (Arachnida: Acariformes) are represented by taxa which include mycophages and predators on nematodes today. The earliest harvestman (Arachnida: Opiliones) includes the first preserved tracheae, and male and female genitalia. Myriapods are represented by a scutigeromorph centipede (Chilopoda: Scutigeromorpha), probably a cursorial predator on the substrate, and a putative millipede (Diplopoda). The oldest springtails (Hexapoda: Collembola) were probably mycophages, and another hexapod of uncertain affinities preserves a gut infill of phytodebris. The first true insects (Hexapoda: Insecta) are represented by a species known from chewing (non-carnivorous?) mandibles. Coprolites also provide insights into diet, and we challenge previous assumptions that several taxa were spore-feeders. Rhynie appears to preserve a largely intact community of terrestrial animals, although some expected groups are absent. The known fossils are (ecologically) consistent with at least part of the fauna found around modern Icelandic hot springs.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254957, year = {2018}, author = {Haug, C}, title = {Feeding strategies in arthropods from the Rhynie and Windyfield cherts: ecological diversification in an early non-marine biota.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254957}, issn = {1471-2970}, mesh = {Animals ; Arthropods/*physiology ; *Biological Evolution ; Ecosystem ; Feeding Behavior ; *Fossils ; Scotland ; }, abstract = {The key to understanding fossil ecosystems is to understand the life habits of long extinct organisms. Yet, as direct observations are no longer possible, morphological details are usually the only available data source. One important aspect of lifestyle is feeding strategies, which can be inferred from morphological structures in comparison with those of extant relatives. The Lower Devonian Rhynie and Windyfield cherts preserve even minute structures to a high degree of detail, which allows investigation of the functional morphology of structures possibly involved in feeding. In this contribution, the feeding structures of different arthropods from the Rhynie and Windyfield cherts are described and the corresponding feeding strategies of the animals are discussed. This overview illustrates that in this early non-marine biota, a wide range of feeding strategies already existed.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254956, year = {2018}, author = {Wellman, CH}, title = {Palaeoecology and palaeophytogeography of the Rhynie chert plants: further evidence from integrated analysis of in situ and dispersed spores.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254956}, issn = {1471-2970}, mesh = {*Ecosystem ; Embryophyta/anatomy & histology/*classification/physiology ; Fossils/*anatomy & histology ; *Hot Springs ; Paleontology ; Scotland ; }, abstract = {The remarkably preserved Rhynie chert plants remain pivotal to our understanding of early land plants. The extraordinary anatomical detail they preserve is a consequence of exceptional preservation, by silicification, in the hot-springs environment they inhabited. However, this has prompted questions as to just how typical of early land plants the Rhynie chert plants really are. Some have suggested that they were highly adapted to the unusual hot-springs environment and are unrepresentative of 'normal' plants of the regional flora. New quantitative analysis of dispersed spore assemblages from the stratigraphical sequence of the Rhynie outlier, coupled with characterization of the in situ spores of the Rhynie chert plants, permits investigation of their palaeoecology and palaeophytogeography. It is shown that the Rhynie inland intermontane basin harboured a relatively diverse flora with only a small proportion of these plants actually inhabiting the hot-springs environment. However, the flora of the Rhynie basin differed from coeval lowland floodplain deposits on the same continent, as it was less diverse, lacked some important spore groups and contained some unique elements. At least some of the Rhynie plants (e.g. Horneophyton lignieri) existed outside the hot-springs environment, inhabiting the wider basin, and were indeed palaeogeographically widespread. They probably existed in the hot-springs environment because they were preadapted to this unstable and harsh setting.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254955, year = {2018}, author = {Channing, A}, title = {A review of active hot-spring analogues of Rhynie: environments, habitats and ecosystems.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254955}, issn = {1471-2970}, mesh = {*Ecosystem ; *Hot Springs ; Paleontology ; *Plants/classification ; Wyoming ; }, abstract = {The Lower Devonian Rhynie chert formed as silica sinter entombed an early terrestrial ecosystem. Silica sinter precipitates only from water flowing from alkali-chloride hot springs and geysers, the surface expression of crustal-scale geothermal systems that form low-sulfidation mineral deposits in the shallow subsurface. Active alkali-chloride hot springs at Yellowstone National Park create a suite of geothermally influenced environments; vent pools, sinter aprons, run-off streams, supra-apron terrace pools and geothermal wetlands that are habitats for modern hot-spring ecosystems. The plant-rich chert, which makes Rhynie internationally famous, probably formed in low-temperature environments at the margins of a sinter apron where frequent flooding by geothermal water and less frequent flooding by river waters created ephemeral to permanent wetland conditions. Here, the plants and associated microbes and animals would be immersed in waters with elevated temperature, brackish salinity, high pH and a cocktail of phytotoxic elements which created stresses that the fossil ecosystem must have tolerated. The environment excluded coeval mesophytic plants, creating a low-diversity hot-spring flora. Comparison with Yellowstone suggests the Rhynie plants were preadapted to their environment by life in more common and widespread environments with elevated salinity and pH such as coastal marshes, salt lakes, estuaries and saline seeps.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254954, year = {2018}, author = {Edwards, D and Kenrick, P and Dolan, L}, title = {History and contemporary significance of the Rhynie cherts-our earliest preserved terrestrial ecosystem.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1739}, pages = {}, pmid = {29254954}, issn = {1471-2970}, mesh = {*Biological Evolution ; *Ecosystem ; *Embryophyta ; *Fossils ; Geology ; Paleontology ; Scotland ; }, abstract = {The Rhynie cherts Unit is a 407 million-year old geological site in Scotland that preserves the most ancient known land plant ecosystem, including associated animals, fungi, algae and bacteria. The quality of preservation is astonishing, and the initial description of several plants 100 years ago had a huge impact on botany. Subsequent discoveries provided unparalleled insights into early life on land. These include the earliest records of plant life cycles and fungal symbioses, the nature of soil microorganisms and the diversity of arthropods. Today the Rhynie chert (here including the Rhynie and Windyfield cherts) takes on new relevance, especially in relation to advances in the fields of developmental genetics and Earth systems science. New methods and analytical techniques also contribute to a better understanding of the environment and its organisms. Key discoveries are reviewed, focusing on the geology of the site, the organisms and the palaeoenvironments. The plants and their symbionts are of particular relevance to understanding the early evolution of the plant life cycle and the origins of fundamental organs and tissue systems. The Rhynie chert provides remarkable insights into the structure and interactions of early terrestrial communities, and it has a significant role to play in developing our understanding of their broader impact on Earth systems.This article is part of a discussion meeting issue 'The Rhynie cherts: our earliest terrestrial ecosystem revisited'.}, } @article {pmid29254745, year = {2018}, author = {Che, R and Zhang, J and Nepal, M and Han, B and Fei, P}, title = {Multifaceted Fanconi Anemia Signaling.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {3}, pages = {171-183}, pmid = {29254745}, issn = {0168-9525}, support = {R01 CA136532/CA/NCI NIH HHS/United States ; R01 CA188251/CA/NCI NIH HHS/United States ; }, mesh = {*DNA Damage ; *DNA Repair ; Fanconi Anemia/*genetics/metabolism/pathology ; Fanconi Anemia Complementation Group Proteins/genetics/metabolism ; Humans ; Models, Genetic ; Mutation ; Signal Transduction/*genetics ; }, abstract = {In 1927 Guido Fanconi described a hereditary condition presenting panmyelopathy accompanied by short stature and hyperpigmentation, now better known as Fanconi anemia (FA). With this discovery the genetic and molecular basis underlying FA has emerged as a field of great interest. FA signaling is crucial in the DNA damage response (DDR) to mediate the repair of damaged DNA. This has attracted a diverse range of investigators, especially those interested in aging and cancer. However, recent evidence suggests FA signaling also regulates functions outside the DDR, with implications for many other frontiers of research. We discuss here the characteristics of FA functions and expand upon current perspectives regarding the genetics of FA, indicating that FA plays a role in a myriad of molecular and cellular processes.}, } @article {pmid29253532, year = {2018}, author = {Choi, H and Shin, S and Jung, S and Clarke, DJ and Lee, S}, title = {Molecular phylogeny of Macrosiphini (Hemiptera: Aphididae): An evolutionary hypothesis for the Pterocomma-group habitat adaptation.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {12-22}, doi = {10.1016/j.ympev.2017.12.021}, pmid = {29253532}, issn = {1095-9513}, mesh = {*Adaptation, Physiological ; Animals ; Aphids/*classification ; Base Sequence ; Bayes Theorem ; Databases as Topic ; *Ecosystem ; Likelihood Functions ; *Models, Biological ; *Phylogeny ; }, abstract = {The aphid tribe Macrosiphini Wilson, 1910 (Hemiptera: Aphididae: Aphidinae) is one of the most controversial groups within Aphididae. We sequenced 2876 bp from one nuclear gene (EF-1α) and four mitochondrial genes (COI, tRNA + COII, 16S) from 107 terminal taxa representing 57 genera of Macrosiphini s.l. (the former Macrosiphini + genera in former Pterocommatini), including all of the recognized major genera and outgroups, and reconstructed the phylogeny using maximum likelihood, maximum parsimony and Bayesian methods. The stepping-stone method was used to evaluate various topological hypotheses regarding Macrosiphini s.l. and related groups. Our findings support both the monophyly of Macrosiphini s.l., and of two subordinate groups (Macrosiphini s.str and the Pterocomma-group), as well as the transfer of Capitophorus, Pleotrichophorus, Liosomaphis and Vesiculaphis to the Pterocomma-group-a result not previously suggested by analyses of molecular data. Ancestral state reconstructions for Macrosiphini and the Pterocomma-group suggest an ancestral primary host association with Rosales and Malpighiales, respectively, and other host associations within the tribe. Host transitions independently occurred more than once in Macrosiphini s.str. Furthermore, host-shifts between Rosales and Malpighiales may have occurred at least once in the Pterocomma-group. Additionally, the Macrosiphini phylogeny indicates that host associations are consistent also with host ecology, with a partitioning of aphid-host relationships into riparian and periaquatic habitats versus drier forest/shrubland habitats.}, } @article {pmid29253505, year = {2018}, author = {Lempereur, A and Canto, PY and Richard, C and Martin, S and Thalgott, J and Raymond, K and Lebrin, F and Drevon, C and Jaffredo, T}, title = {The TGFβ pathway is a key player for the endothelial-to-hematopoietic transition in the embryonic aorta.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {292-303}, doi = {10.1016/j.ydbio.2017.12.006}, pmid = {29253505}, issn = {1095-564X}, mesh = {Animals ; Aorta/cytology/*embryology ; Avian Proteins/*metabolism ; Chick Embryo ; Chickens ; Endothelium, Vascular/cytology/*embryology ; Hematopoiesis, Extramedullary/*physiology ; Protein-Serine-Threonine Kinases/metabolism ; Receptor, Transforming Growth Factor-beta Type II ; Receptors, Transforming Growth Factor beta/metabolism ; Signal Transduction/*physiology ; Smad1 Protein/metabolism ; Smad5 Protein/metabolism ; Transforming Growth Factor beta/*metabolism ; }, abstract = {The embryonic aorta produces hematopoietic stem and progenitor cells from a hemogenic endothelium localized in the aortic floor through an endothelial to hematopoietic transition. It has been long proposed that the Bone Morphogenetic Protein (BMP)/Transforming Growth Factor ß (TGFß) signaling pathway was implicated in aortic hematopoiesis but the very nature of the signal was unknown. Here, using thorough expression analysis of the BMP/TGFß signaling pathway members in the endothelial and hematopoietic compartments of the aorta at pre-hematopoietic and hematopoietic stages, we show that the TGFß pathway is preferentially balanced with a prominent role of Alk1/TgfßR2/Smad1 and 5 on both chicken and mouse species. Functional analysis using embryonic stem cells mutated for Acvrl1 revealed an enhanced propensity to produce hematopoietic cells. Collectively, we reveal that TGFß through the Alk1/TgfßR2 receptor axis is acting on endothelial cells to produce hematopoiesis.}, } @article {pmid29253197, year = {2018}, author = {Campitelli, BE and Kenney, AM and Hopkins, R and Soule, J and Lovell, JT and Juenger, TE}, title = {Genetic Mapping Reveals an Anthocyanin Biosynthesis Pathway Gene Potentially Influencing Evolutionary Divergence between Two Subspecies of Scarlet Gilia (Ipomopsis aggregata).}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {807-822}, doi = {10.1093/molbev/msx318}, pmid = {29253197}, issn = {1537-1719}, abstract = {Immense floral trait variation has likely arisen as an adaptation to attract pollinators. Different pollinator syndromes-suites of floral traits that attract specific pollinator functional groups-are repeatedly observed across closely related taxa or divergent populations. The observation of these trait syndromes suggests that pollinators use floral cues to signal the underlying nectar reward, and that complex trait combinations may persist and evolve through genetic correlations. Here, we explore pollinator preferences and the genetic architecture of floral divergence using an extensive genetic mapping study in the hybrid zone of two Ipomopsis aggregata subspecies that exhibit a hummingbird and a hawkmoth pollinator syndrome. We found that natural selection acts on several floral traits, and that hummingbirds and hawkmoths exhibited flower color preferences as predicted by their respective pollinator syndromes. Our quantitative trait loci (QTL) analyses revealed 46 loci affecting floral features, many of which colocalize across the genome. Two of these QTL have large effects explaining >15% of the phenotypic variance. The strongest QTL was associated with flower color and localized to a SNP in the anthocyanin biosynthesis pathway gene, dihydroflavonol-4-reductase (DFR). Further analysis revealed strong associations between DFR SNP variants, gene expression, and flower color across populations from the hybrid zone. Hence, DFR may be a target of pollinator-mediated selection in the hybrid zone of these two subspecies. Together, our findings suggest that hummingbirds and hawkmoths exhibit contrasting flower color preferences, which may drive the divergence of several floral traits through correlated trait evolution.}, } @article {pmid29251590, year = {2018}, author = {Kim, DU and Lee, H and Lee, S and Park, S and Yoon, JH and Ka, JO}, title = {Spirosoma metallilatum sp. nov., isolated from an automotive air conditioning system.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {523-528}, doi = {10.1099/ijsem.0.002533}, pmid = {29251590}, issn = {1466-5034}, mesh = {*Air Conditioning ; Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Motor Vehicles ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, rod-shaped and yellow-pigmented bacterial strain, designated TX0405T, was isolated from an automotive air conditioning system. Colonies were circular, convex, semi-translucent, smooth and yellow. The strain grew at 20-28°C (optimum, 28°C), at pH 6.0-7.5 (optimum, pH 6.5) and in the presence of 0-1 % (w/v) NaCl. Phylogenetic analysis based on 16S rRNA gene sequence indicated that the strain was grouped with the members of the genus Spirosoma, with the sequence similarities of 93.0 and 92.3 % with Spirosoma panaciterrae DSM 21099T and Spirosoma swuense JBM2-3T, respectively. The major fatty acids of the strain were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) (33.2 %), C16 : 1ω5c (25.4 %), iso-C15 : 0 (15.0 %), C16 : 0 (6.5 %) and iso-C17 : 0 3-OH (6.2 %). The predominant menaquinone was MK-7. The polar lipids were phosphatidylethanolamine, an unidentified aminolipid, two unidentified aminophospholipids and three unidentified lipids. The DNA G+C content of the type strain was 51.9 mol%. On the basis of the data presented, strain TX0405T represents a novel species of the genus Spirosoma, for which the name Spirosomametallilatum sp. nov. (=KACC 19012T=NBRC 112493T) is proposed.}, } @article {pmid29251588, year = {2018}, author = {Zhou, MY and Zhang, YJ and Zhang, XY and Yang, XD and He, HL and Ning, D and Du, Z}, title = {Flavobacterium phocarum sp. nov., isolated from soils of a seal habitat in Antarctica.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {536-541}, doi = {10.1099/ijsem.0.002535}, pmid = {29251588}, issn = {1466-5034}, mesh = {Animals ; Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; *Seals, Earless ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, yellow-pigmented, non-flagellated, gliding, rod-shaped, oxidase-negative and catalase-positive bacterium, designated SE14T, was isolated from soil on King George Island, South Shetland Islands, Antarctica. Strain SE14T grew at 4-25 °C (optimum, 20 °C), at pH 6.0-9.0 (optimum, pH 7.0-7.5) and with 0-3.0 % NaCl (optimum, 1.0-1.5 %), and could not produce flexirubin-type pigments. 16S rRNA gene sequence analysis showed the the isolate belonged to the genus Flavobacterium. Strain SE14T had the highest 16S rRNA gene sequence similarity to Flavobacterium antarcticum, F. tegetincola and F. degerlachei with 95.8, 95.5 and 95.2 %, respectively. The strain SE14T consisted of a clade with Flavobacteriumnoncentrifugens (16S rRNA gene sequence similarity 94.9 %) and F. qiangtangense (16S rRNA gene sequence similarity 94.2 %) and simultaneously formed a distinct phyletic lineage in the neighbour-joining phylogenetic tree. Polar lipids of the strain included phosphatidylethanolamine and four unidentified aminolipids. Strain SE14T contained anteiso-C15 : 0, iso-C15 : 0 and a mixture of iso-C15 : 0 2-OH and/or C16 : 1ω7c as the main fatty acids, and the only respiratory quinone was menaquinone-6. The genomic DNA G+C content was 42.3 mol%. The polyphasic taxonomic study revealed that strain SE14T belongs to a novel species within the genus Flavobacterium , and the name Flavobacterium phocarum sp. nov. is proposed. The type strain is SE14T (=CCTCC AB 2017225T=KCTC 52612T).}, } @article {pmid29249815, year = {2018}, author = {Burgess, DJ}, title = {Translational genetics: CRISPR therapies - making the grade not the cut.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {63}, pmid = {29249815}, issn = {1471-0064}, } @article {pmid29249814, year = {2018}, author = {Zlotorynski, E}, title = {Splicing: Going in circles.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {64-65}, pmid = {29249814}, issn = {1471-0064}, } @article {pmid29249813, year = {2018}, author = {Xie, K and Dalbey, RE}, title = {Inserting proteins into the bacterial cytoplasmic membrane using the Sec and YidC translocases.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {120}, pmid = {29249813}, issn = {1740-1534}, abstract = {This corrects the article DOI: 10.1038/nrmicro3595.}, } @article {pmid29249812, year = {2018}, author = {Harding, CM and Hennon, SW and Feldman, MF}, title = {Uncovering the mechanisms of Acinetobacter baumannii virulence.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {91-102}, pmid = {29249812}, issn = {1740-1534}, abstract = {Acinetobacter baumannii is a nosocomial pathogen that causes ventilator-associated as well as bloodstream infections in critically ill patients, and the spread of multidrug-resistant Acinetobacter strains is cause for concern. Much of the success of A. baumannii can be directly attributed to its plastic genome, which rapidly mutates when faced with adversity and stress. However, fundamental virulence mechanisms beyond canonical drug resistance were recently uncovered that enable A. baumannii and, to a limited extent, other medically relevant Acinetobacter species to successfully thrive in the health-care environment. In this Review, we explore the molecular features that promote environmental persistence, including desiccation resistance, biofilm formation and motility, and we discuss the most recently identified virulence factors, such as secretion systems, surface glycoconjugates and micronutrient acquisition systems that collectively enable these pathogens to successfully infect their hosts.}, } @article {pmid29249696, year = {2018}, author = {Brown, N and Sandholm, T}, title = {Superhuman AI for heads-up no-limit poker: Libratus beats top professionals.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {418-424}, doi = {10.1126/science.aao1733}, pmid = {29249696}, issn = {1095-9203}, mesh = {Algorithms ; *Artificial Intelligence ; *Games, Recreational ; Humans ; }, abstract = {No-limit Texas hold'em is the most popular form of poker. Despite artificial intelligence (AI) successes in perfect-information games, the private information and massive game tree have made no-limit poker difficult to tackle. We present Libratus, an AI that, in a 120,000-hand competition, defeated four top human specialist professionals in heads-up no-limit Texas hold'em, the leading benchmark and long-standing challenge problem in imperfect-information game solving. Our game-theoretic approach features application-independent techniques: an algorithm for computing a blueprint for the overall strategy, an algorithm that fleshes out the details of the strategy for subgames that are reached during play, and a self-improver algorithm that fixes potential weaknesses that opponents have identified in the blueprint strategy.}, } @article {pmid29249600, year = {2018}, author = {Cicin-Sain, L and Arens, R}, title = {Exhaustion and Inflation at Antipodes of T Cell Responses to Chronic Virus Infection.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {498-509}, doi = {10.1016/j.tim.2017.11.012}, pmid = {29249600}, issn = {1878-4380}, abstract = {Viruses that have coevolved with their host establish chronic infections that are well tolerated by the host. Other viruses, that are partly adapted to their host, may induce chronic infections where persistent replication and viral antigen expression occur. The former induce highly functional and resilient CD8T cell responses called memory inflation. The latter induce dysfunctional and exhausted responses. The reasons compelling T cell responses towards inflationary or exhausted responses are only partly understood. In this review we compare the two conditions and describe mechanistic similarities and differences. We also provide a list of potential reasons why exhaustion or inflation occur in different virus infections. We propose that T cell-mediated transcriptional repression of viral gene expression provides a critical feature of inflation that allows peaceful virus and host coexistence. The virus is controlled, but its genome is not eradicated. If this mechanism is not available, as in the case of RNA viruses, the virus and the host are compelled to an arms race. If virus proliferation and spread proceed uncontrolled for too long, T cells are forced to strike a balance between viral control and tissue destruction, losing antiviral potency and facilitating virus persistence.}, } @article {pmid29249363, year = {2018}, author = {, and , and Palevich, N and Britton, C and Kamenetzky, L and Mitreva, M and de Moraes Mourão, M and Bennuru, S and Quack, T and Scholte, LLS and Tyagi, R and Slatko, BE}, title = {Tackling Hypotheticals in Helminth Genomes.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {179-183}, doi = {10.1016/j.pt.2017.11.007}, pmid = {29249363}, issn = {1471-5007}, mesh = {Animals ; Genome, Helminth/*genetics ; Genomics/trends ; Helminth Proteins/genetics ; Helminths/*genetics ; Molecular Sequence Annotation ; Sequence Analysis, RNA ; }, abstract = {Advancements in genome sequencing have led to the rapid accumulation of uncharacterized 'hypothetical proteins' in the public databases. Here we provide a community perspective and some best-practice approaches for the accurate functional annotation of uncharacterized genomic sequences.}, } @article {pmid29249333, year = {2018}, author = {Egan, ES}, title = {Beyond Hemoglobin: Screening for Malaria Host Factors.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {133-141}, pmid = {29249333}, issn = {0168-9525}, support = {DP2 HL137186/HL/NHLBI NIH HHS/United States ; }, mesh = {CD55 Antigens/*genetics/immunology ; Cell Differentiation ; Child ; Disease Resistance/*genetics ; Erythrocytes/immunology/metabolism/parasitology ; Female ; Gene Expression ; Genome-Wide Association Study ; Hematopoietic Stem Cells/immunology/metabolism/parasitology ; Host-Pathogen Interactions/*immunology ; Humans ; Hyaluronan Receptors/*genetics/immunology ; Immunity, Innate ; Malaria, Falciparum/*genetics/immunology/parasitology ; Plasmodium falciparum/immunology/*metabolism/pathogenicity ; Pregnancy ; Primary Cell Culture ; Severity of Illness Index ; }, abstract = {Severe malaria is caused by the Apicomplexan parasite Plasmodium falciparum, and results in significant global morbidity and mortality, particularly among young children and pregnant women. P. falciparum exclusively infects human erythrocytes during clinical illness, and several natural erythrocyte polymorphisms are protective against severe malaria. Since erythrocytes are enucleated and lack DNA, genetic approaches to understand erythrocyte determinants of malaria infection have historically been limited. This review highlights recent advances in the use of hematopoietic stem cells to facilitate genetic screening for malaria host factors. While challenges still exist, this approach holds promise for gaining new insights into host-pathogen interactions in malaria.}, } @article {pmid29249332, year = {2018}, author = {Sun, Q and Hao, Q and Prasanth, KV}, title = {Nuclear Long Noncoding RNAs: Key Regulators of Gene Expression.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {142-157}, pmid = {29249332}, issn = {0168-9525}, support = {R01 GM088252/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Nucleus/*genetics/metabolism ; Chromatin/*chemistry/metabolism ; Chromosomal Proteins, Non-Histone/genetics/metabolism ; Humans ; Neoplasms/*genetics/metabolism/pathology ; Polycomb-Group Proteins/genetics/metabolism ; RNA Processing, Post-Transcriptional ; RNA, Long Noncoding/classification/*genetics/metabolism ; Transcription Factors/genetics/metabolism ; *Transcription, Genetic ; X Chromosome Inactivation ; }, abstract = {A significant portion of the human genome encodes genes that transcribe long nonprotein-coding RNAs (lncRNAs). A large number of lncRNAs localize in the nucleus, either enriched on the chromatin or localized to specific subnuclear compartments. Nuclear lncRNAs participate in several biological processes, including chromatin organization, and transcriptional and post-transcriptional gene expression, and also act as structural scaffolds of nuclear domains. Here, we highlight recent studies demonstrating the role of lncRNAs in regulating gene expression and nuclear organization in mammalian cells. In addition, we update current knowledge about the involvement of the most-abundant and conserved lncRNA, metastasis-associated lung adenocarcinoma transcript 1 (MALAT1), in gene expression control.}, } @article {pmid29249002, year = {2018}, author = {Erkenbrack, EM}, title = {Notch-mediated lateral inhibition is an evolutionarily conserved mechanism patterning the ectoderm in echinoids.}, journal = {Development genes and evolution}, volume = {228}, number = {1}, pages = {1-11}, pmid = {29249002}, issn = {1432-041X}, support = {IOS1240626//Division of Integrative Organismal Systems/International ; }, mesh = {Animals ; Body Patterning ; Embryo, Nonmammalian/chemistry/metabolism ; Gastrulation ; Neural Stem Cells/metabolism ; RNA, Messenger/analysis ; Receptors, Notch/metabolism ; Sea Urchins/chemistry/cytology/*embryology ; }, abstract = {Notch signaling is a crucial cog in early development of euechinoid sea urchins, specifying both non-skeletogenic mesodermal lineages and serotonergic neurons in the apical neuroectoderm. Here, the spatial distributions and function of delta, gcm, and hesc, three genes critical to these processes in euechinoids, are examined in the distantly related cidaroid sea urchin Eucidaris tribuloides. Spatial distribution and experimental perturbation of delta and hesc suggest that the function of Notch signaling in ectodermal patterning in early development of E. tr ibuloides is consistent with canonical lateral inhibition. Delta transcripts were observed in t he archenteron, apical ectoderm, and lateral ectoderm in gastrulating e mbryos of E. tribuloides. Perturbation of Notch signaling by either delta morpholino or treatment of DAPT downregulated hesc and upregulated delta and gcm, resulting in ectopic expression of delta and gcm. Similarly, hesc perturbation mirrored the effects of delta perturbation. Interestingly, perturbation of delta or hesc resulted in more cells expressing gcm and supernumerary pigment cells, suggesting that pigment cell proliferation is regulated by Notch in E. tribuloides. These results are consistent with an evolutionary scenario whereby, in the echinoid ancestor, Notch signaling was deployed in the ectoderm to specify neurogenic progenitors and controlled pigment cell proliferation in the dorsal ectoderm.}, } @article {pmid29248948, year = {2018}, author = {Yodsing, N and Lekphrom, R and Sangsopha, W and Aimi, T and Boonlue, S}, title = {Secondary Metabolites and Their Biological Activity from Aspergillus aculeatus KKU-CT2.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {513-518}, pmid = {29248948}, issn = {1432-0991}, mesh = {Anti-Infective Agents/chemistry/metabolism/*pharmacology ; Antimalarials/chemistry/metabolism/*pharmacology ; Antineoplastic Agents/chemistry/metabolism/*pharmacology ; Aspergillus/*chemistry/*metabolism ; Bacteria/drug effects ; Cell Line, Tumor ; Cell Proliferation/drug effects ; Humans ; Inhibitory Concentration 50 ; Molecular Structure ; Plasmodium falciparum/drug effects ; *Secondary Metabolism ; }, abstract = {The bioactive compounds of the fungus Aspergillus aculeatus strain KKU-CT2, have been studied. The crude extracts from this fungus showed good antimicrobial activity against human pathogens, including Gram-positive and Gram-negative bacteria and yeast-like fungi. Its chemical components were isolated and purified by chromatographic methods. The structures of the secondary metabolites were elucidated by spectroscopic methods (IR, 1H, and 13C NMR). They were identified as ergosterol peroxide (1), secalonic acid D (2), secalonic acid F (3), variecolin (4), variecolactone (5), and ergosterol (6). Compounds 1 and 4-6 are reported for the first time as fungal metabolites from this species. Compound 1 displayed inhibitory effects on HSV-1 with an IC50 of 11.01 μg/ml. Compounds 3, 4, and 6 exhibited antimalarial activity against Plasmodium falciparum with IC50 of 1.03, 1.47, and 5.31 µg/ml, respectively. Additionally, all compounds from A. aculeatus KKU-CT2 showed unprecedented anticancer activities against human epidermoid carcinoma in the mouth (KB) (compounds 1-6), human breast cancer (MCF-7) (compounds 2, 4, and 5), and human lung cancer cells (NCI-H187) (compounds 1-4 and 6). These results suggest that secondary metabolites from A. aculeatus KKU-CT2 might be interesting for further derivatization, targeting diseases such as cancer.}, } @article {pmid29248946, year = {2018}, author = {Diaz Ochoa, JG}, title = {Elastic Multi-scale Mechanisms: Computation and Biological Evolution.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {47-57}, pmid = {29248946}, issn = {1432-1432}, abstract = {Explanations based on low-level interacting elements are valuable and powerful since they contribute to identify the key mechanisms of biological functions. However, many dynamic systems based on low-level interacting elements with unambiguous, finite, and complete information of initial states generate future states that cannot be predicted, implying an increase of complexity and open-ended evolution. Such systems are like Turing machines, that overlap with dynamical systems that cannot halt. We argue that organisms find halting conditions by distorting these mechanisms, creating conditions for a constant creativity that drives evolution. We introduce a modulus of elasticity to measure the changes in these mechanisms in response to changes in the computed environment. We test this concept in a population of predators and predated cells with chemotactic mechanisms and demonstrate how the selection of a given mechanism depends on the entire population. We finally explore this concept in different frameworks and postulate that the identification of predictive mechanisms is only successful with small elasticity modulus.}, } @article {pmid29248627, year = {2018}, author = {Van Steenkiste, NWL and Herbert, ER and Leander, BS}, title = {Species diversity in the marine microturbellarian Astrotorhynchus bifidus sensu lato (Platyhelminthes: Rhabdocoela) from the Northeast Pacific Ocean.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {259-273}, doi = {10.1016/j.ympev.2017.12.012}, pmid = {29248627}, issn = {1095-9513}, mesh = {Animals ; DNA, Protozoan/chemistry/isolation & purification/metabolism ; Electron Transport Complex IV/chemistry/classification/genetics ; Gene Flow ; Haplotypes ; Pacific Ocean ; Phylogeny ; Platyhelminths/*classification/genetics ; RNA, Ribosomal, 18S/chemistry/classification/genetics ; RNA, Ribosomal, 28S/chemistry/classification/genetics ; Sequence Analysis, DNA ; Sympatry/genetics ; }, abstract = {Increasing evidence suggests that many widespread species of meiofauna are in fact regional complexes of (pseudo-)cryptic species. This knowledge has challenged the 'Everything is Everywhere' hypothesis and also partly explains the meiofauna paradox of widespread nominal species with limited dispersal abilities. Here, we investigated species diversity within the marine microturbellarian Astrotorhynchus bifidus sensu lato in the Northeast Pacific Ocean. We used a multiple-evidence approach combining multi-gene (18S, 28S, COI) phylogenetic analyses, several single-gene and multi-gene species delimitation methods, haplotype networks and conventional taxonomy to designate Primary Species Hypotheses (PSHs). This included the development of rhabdocoel-specific COI barcode primers, which also have the potential to aid in species identification and delimitation in other rhabdocoels. Secondary Species Hypotheses (SSHs) corresponding to morphospecies and pseudo-cryptic species were then proposed based on the minimum consensus of different PSHs. Our results showed that (a) there are at least five species in the A. bifidus complex in the Northeast Pacific Ocean, four of which can be diagnosed based on stylet morphology, (b) the A. bifidus complex is a mixture of sympatric and allopatric species with regional and/or subglobal distributions, (c) sympatry occurs on local (sample sites), regional (Northeastern Pacific) and subglobal (Northern Atlantic, Arctic, Northeastern Pacific) scales. Mechanisms for this co-occurrence are still poorly understood, but we hypothesize they could include habitat differentiation (spatial and/or seasonal) and life history characteristics such as sexual selection and dispersal abilities. Our results also suggest the need for improved sampling and exploration of molecular markers to accurately map gene flow and broaden our understanding of species diversity and distribution of microturbellarians in particular and meiofauna in general.}, } @article {pmid29248626, year = {2018}, author = {Justi, SA and Cahan, S and Stevens, L and Monroy, C and Lima-Cordón, R and Dorn, PL}, title = {Vectors of diversity: Genome wide diversity across the geographic range of the Chagas disease vector Triatoma dimidiata sensu lato (Hemiptera: Reduviidae).}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {144-150}, pmid = {29248626}, issn = {1095-9513}, support = {R03 AI126268/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Central America ; Chagas Disease/parasitology/pathology ; DNA/chemistry/isolation & purification/metabolism ; Genes, Mitochondrial ; *Genetic Variation ; *Genome ; Humans ; Insect Vectors/genetics ; Phylogeny ; Polymorphism, Single Nucleotide ; Triatoma/classification/*genetics/parasitology ; Trypanosoma cruzi/physiology ; }, abstract = {To date, the phylogeny of Triatoma dimidiata sensu lato (s. l.) (Hemiptera: Reduviidae: Triatominae), the epidemiologically most important Chagas disease vector in Central America and a secondary vector in Mexico and northern South America, has only been investigated by one multi-copy nuclear gene (Internal Transcribed Spacer - 2) and a few mitochondrial genes. We examined 450 specimens sampled across most of its native range from Mexico to Ecuador using reduced representation next-generation sequencing encompassing over 16,000 single nucleotide polymorphisms (SNPs). Using a combined phylogenetic and species delimitation approach we uncovered two distinct species, as well as a well-defined third group that may contain multiple species. The findings are discussed with respect to possible drivers of diversification and the epidemiological importance of the distinct species and groups.}, } @article {pmid29248625, year = {2018}, author = {Pardo-Gandarillas, MC and Torres, FI and Fuchs, D and Ibáñez, CM}, title = {Updated molecular phylogeny of the squid family Ommastrephidae: Insights into the evolution of spawning strategies.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {212-217}, doi = {10.1016/j.ympev.2017.12.014}, pmid = {29248625}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Cytochromes b/classification/genetics ; Decapodiformes/*classification/genetics ; Electron Transport Complex IV/classification/genetics ; *Evolution, Molecular ; Phylogeny ; RNA, Ribosomal, 16S/classification/genetics ; RNA, Ribosomal, 18S/classification/genetics ; }, abstract = {Two types of spawning strategy have been described for ommastrephid squids: coastal and oceanic. It has been suggested that ancestral ommastrephids inhabited coastal waters and expanded their distribution into the open ocean during global changes in ocean circulation in the Oligocene. This hypothesis could explain the different reproductive strategies in oceanic squids, but has never been tested in a phylogenetic context. In the present study, we assess the coastal-to-open-ocean hypothesis through inferring the evolution of reproductive traits (spawning type) of ommastrephid squids using the phylogenetic comparative method to estimate ancestral states and divergence times. This analysis was performed using a robust molecular phylogeny with three mitochondrial genes (COI, CYTB and 16S) and two nuclear genes (RHO and 18S) for nearly all species of ommastrephid squid. Our results support dividing the Ommastrephidae into the three traditional subfamilies, plus the monotypic subfamily Todaropsinae as proposed previously. Divergence times were found to be older than those suggested. Our analyses strongly suggest that early ommastrephid squids spawned in coastal areas, with some species subsequently switching to spawn in oceanic areas, supporting previous non-tested hypotheses. We found evidence of gradual evolution change of spawning type in ommastrephid squids estimated to have occurred since the Cretaceous.}, } @article {pmid29248439, year = {2018}, author = {Zhang, HE and Gall, MG and Gorrell, MD}, title = {Letter to Editor.}, journal = {Developmental biology}, volume = {439}, number = {1}, pages = {1}, doi = {10.1016/j.ydbio.2017.12.009}, pmid = {29248439}, issn = {1095-564X}, } @article {pmid29248438, year = {2018}, author = {Kim, M and Ksiazek, I}, title = {Response to Letter to the Editor.}, journal = {Developmental biology}, volume = {439}, number = {1}, pages = {2}, doi = {10.1016/j.ydbio.2017.12.010}, pmid = {29248438}, issn = {1095-564X}, } @article {pmid29248328, year = {2018}, author = {Snelgrove, PVR and Soetaert, K and Solan, M and Thrush, S and Wei, CL and Danovaro, R and Fulweiler, RW and Kitazato, H and Ingole, B and Norkko, A and Parkes, RJ and Volkenborn, N}, title = {Global Carbon Cycling on a Heterogeneous Seafloor.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {2}, pages = {96-105}, doi = {10.1016/j.tree.2017.11.004}, pmid = {29248328}, issn = {1872-8383}, mesh = {*Carbon Cycle ; Chemistry ; Geology ; Marine Biology ; Models, Biological ; *Oceans and Seas ; }, abstract = {Diverse biological communities mediate the transformation, transport, and storage of elements fundamental to life on Earth, including carbon, nitrogen, and oxygen. However, global biogeochemical model outcomes can vary by orders of magnitude, compromising capacity to project realistic ecosystem responses to planetary changes, including ocean productivity and climate. Here, we compare global carbon turnover rates estimated using models grounded in biological versus geochemical theory and argue that the turnover estimates based on each perspective yield divergent outcomes. Importantly, empirical studies that include sedimentary biological activity vary less than those that ignore it. Improving the relevance of model projections and reducing uncertainty associated with the anticipated consequences of global change requires reconciliation of these perspectives, enabling better societal decisions on mitigation and adaptation.}, } @article {pmid29247849, year = {2018}, author = {Buckner, JC and Ellingson, R and Gold, DA and Jones, TL and Jacobs, DK}, title = {Mitogenomics supports an unexpected taxonomic relationship for the extinct diving duck Chendytes lawi and definitively places the extinct Labrador Duck.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {102-109}, doi = {10.1016/j.ympev.2017.12.008}, pmid = {29247849}, issn = {1095-9513}, support = {T32 HG002536/HG/NHGRI NIH HHS/United States ; }, mesh = {Animals ; Bayes Theorem ; Biological Evolution ; Ducks/*classification/*genetics ; Extinction, Biological ; Feeding Behavior ; Genome, Mitochondrial/*genetics ; *Genomics ; Phylogeny ; }, abstract = {Chendytes lawi, an extinct flightless diving anseriform from coastal California, was traditionally classified as a sea duck, tribe Mergini, based on similarities in osteological characters. We recover and analyze mitochondrial genomes of C. lawi and five additional Mergini species, including the extinct Labrador Duck, Camptorhynchus labradorius. Despite its diving morphology, C. lawi is reconstructed as an ancient relictual lineage basal to the dabbling ducks (tribe Anatini), revealing an additional example of convergent evolution of characters related to feeding behavior among ducks. The Labrador Duck is sister to Steller's Eider which may provide insights into the evolution and ecology of this poorly known extinct species. Our results demonstrate that inclusion of full length mitogenomes, from taxonomically distributed ancient and modern sources can improve phylogeny reconstruction of groups previously assessed with shorter single-gene mitochondrial sequences.}, } @article {pmid29247848, year = {2018}, author = {Sherpa, S and Ansart, A and Madec, L and Martin, MC and Dréano, S and Guiller, A}, title = {Refining the biogeographical scenario of the land snail Cornu aspersum aspersum: Natural spatial expansion and human-mediated dispersal in the Mediterranean basin.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {218-232}, doi = {10.1016/j.ympev.2017.12.018}, pmid = {29247848}, issn = {1095-9513}, mesh = {Africa, Northern ; Animals ; Bayes Theorem ; Cytochromes b/chemistry/classification/genetics ; DNA, Mitochondrial/chemistry/classification/genetics ; Europe ; Genetic Variation ; Haplotypes ; Humans ; Mediterranean Region ; Microsatellite Repeats/genetics ; Phylogeny ; Phylogeography ; Principal Component Analysis ; RNA, Ribosomal, 16S/chemistry/classification/genetics ; Snails/anatomy & histology/*classification/genetics ; }, abstract = {The land snail Cornu aspersum aspersum, native to the Mediterranean region, has been the subject of several anatomical and molecular studies leading to recognize two divergent lineages, named "East" and "West" according to their geographical distribution in North Africa. The first biogeographical scenario proposed the role of Oligocene paleogeographic events and Quaternary glacial refugia to explain spatial patterns of genetic variation. The aim of this study was to refine this scenario using molecular and morphometric data from 169 populations sampled across Mediterranean islands and continents. The two previously described lineages no longer correspond to distinct biogeographical entities. Phylogenetic relationships reveal the existence of seven clades, do not support the Tyrrhenian vicariance hypothesis, and suggest that C. a. aspersum most likely originates from North Africa. We found two contrasted patterns with the seven clades defining spatially well-structured populations in the southern Mediterranean whereas one clade is distributed across the basin. High genetic diversities and rates of endemism in North Africa support the role of this region for the diversification of C. a. aspersum. In referring to divergence times previously estimated, we suggest allopatric differentiation due to geological changes of the Atlas system and multiple refugial areas during Pleistocene glaciations. The new biogeographical scenario implies an initial range expansion from North Africa to the Iberian Peninsula and the peri-Tyrrhenian regions through land bridges connections during the Messinian Salinity Crisis and Pleistocene glaciations. Historical events appear to have also structured morphometric variation but recent dispersal events favored the emergence of secondary contacts between clades. Southern Mediterranean clades are limited to their initial distribution and populations of the recent clade would have rapidly recolonized the whole Mediterranean in the Holocene due to greater adaptive potential and the influence of human transportations.}, } @article {pmid29247847, year = {2018}, author = {Peters, RS and Niehuis, O and Gunkel, S and Bläser, M and Mayer, C and Podsiadlowski, L and Kozlov, A and Donath, A and van Noort, S and Liu, S and Zhou, X and Misof, B and Heraty, J and Krogmann, L}, title = {Transcriptome sequence-based phylogeny of chalcidoid wasps (Hymenoptera: Chalcidoidea) reveals a history of rapid radiations, convergence, and evolutionary success.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {286-296}, doi = {10.1016/j.ympev.2017.12.005}, pmid = {29247847}, issn = {1095-9513}, mesh = {Animals ; Evolution, Molecular ; Fossils ; High-Throughput Nucleotide Sequencing ; Ovum/metabolism ; *Phylogeny ; RNA/chemistry/isolation & purification/metabolism ; Sequence Analysis, RNA ; *Transcriptome ; Wasps/*classification/genetics ; }, abstract = {Chalcidoidea are a megadiverse group of mostly parasitoid wasps of major ecological and economical importance that are omnipresent in almost all extant terrestrial habitats. The timing and pattern of chalcidoid diversification is so far poorly understood and has left many important questions on the evolutionary history of Chalcidoidea unanswered. In this study, we infer the early divergence events within Chalcidoidea and address the question of whether or not ancestral chalcidoids were small egg parasitoids. We also trace the evolution of some key traits: jumping ability, development of enlarged hind femora, and associations with figs. Our phylogenetic inference is based on the analysis of 3,239 single-copy genes across 48 chalcidoid wasps and outgroups representatives. We applied an innovative a posteriori evaluation approach to molecular clock-dating based on nine carefully validated fossils, resulting in the first molecular clock-based estimation of deep Chalcidoidea divergence times. Our results suggest a late Jurassic origin of Chalcidoidea, with a first divergence of morphologically and biologically distinct groups in the early to mid Cretaceous, between 129 and 81 million years ago (mya). Diversification of most extant lineages happened rapidly after the Cretaceous in the early Paleogene, between 75 and 53 mya. The inferred Chalcidoidea tree suggests a transition from ancestral minute egg parasitoids to larger-bodied parasitoids of other host stages during the early history of chalcidoid evolution. The ability to jump evolved independently at least three times, namely in Eupelmidae, Encyrtidae, and Tanaostigmatidae. Furthermore, the large-bodied strongly sclerotized species with enlarged hind femora in Chalcididae and Leucospidae are not closely related. Finally, the close association of some chalcidoid wasps with figs, either as pollinators, or as inquilines/gallers or as parasitoids, likely evolved at least twice independently: in the Eocene, giving rise to fig pollinators, and in the Oligocene or Miocene, resulting in non-pollinating fig-wasps, including gallers and parasitoids. The origins of very speciose lineages (e.g., Mymaridae, Eulophidae, Pteromalinae) are evenly spread across the period of chalcidoid evolution from early Cretaceous to the late Eocene. Several shifts in biology and morphology (e.g., in host exploitation, body shape and size, life history), each followed by rapid radiations, have likely enabled the evolutionary success of Chalcidoidea.}, } @article {pmid29247620, year = {2018}, author = {Ashe, S and Malhotra, V and Raghu, P}, title = {Protein kinase D regulates metabolism and growth by controlling secretion of insulin like peptide.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {175-185}, doi = {10.1016/j.ydbio.2017.12.008}, pmid = {29247620}, issn = {1095-564X}, mesh = {Animals ; Brain/*embryology ; Drosophila Proteins/genetics/*metabolism ; Drosophila melanogaster ; Inhibitor of Apoptosis Proteins/genetics/*metabolism ; Insulin-Like Growth Factor I/genetics/*metabolism ; Larva/genetics/metabolism ; Neurosecretory Systems/*embryology ; Protein Kinase C/genetics/*metabolism ; }, abstract = {Mechanisms coupling growth and metabolism are conserved in Drosophila and mammals. In metazoans, such coupling is achieved across tissue scales through the regulated secretion of chemical messengers such as insulin that control the metabolism and growth of cells. Although the regulated secretion of Insulin like peptide (dILP) is key to normal growth and metabolism in Drosophila, the sub-cellular mechanisms that regulate dILP release remain poorly understood. We find that reduced function of the only protein kinase D in Drosophila (dPKDH) results in delayed larval growth and development associated with abnormal sugar and lipid metabolism, reduced insulin signalling and accumulation of dILP2 in the neurosecretory IPCs of the larval brain. These phenotypes are rescued by tissue-selective reconstitution of dPKD in the neurosecretory cells of dPKDH. Selective downregulation of dPKD activity in the neurosecretory IPCs phenocopies the growth defects, metabolic abnormalities and dILP2 accumulation seen in dPKDH. Thus, dPKD mediated secretion of dILP2 from neurosecretory cells during development is necessary for normal larval growth.}, } @article {pmid29247337, year = {2018}, author = {Di Lodovico, S and Del Vecchio, A and Cataldi, V and Di Campli, E and Di Bartolomeo, S and Cellini, L and Di Giulio, M}, title = {Microbial Contamination of Smartphone Touchscreens of Italian University Students.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {336-342}, pmid = {29247337}, issn = {1432-0991}, mesh = {Adolescent ; Bacteria/classification/genetics/growth & development/*isolation & purification ; Colony Count, Microbial ; Equipment Contamination/*statistics & numerical data ; Female ; Humans ; Italy ; Male ; *Smartphone/instrumentation ; Students ; Universities ; Young Adult ; }, abstract = {In this study, the microbial contamination of smartphones from Italian University students was analyzed. A total of 100 smartphones classified as low, medium, and high emission were examined. Bacteria were isolated on elective and selective media and identified by biochemical tests. The mean values of cfu/cm2 were 0.79 ± 0.01; in particular, a mean of 1.21 ± 0.12, 0.77 ± 0.1 and 0.40 ± 0.10 cfu/cm2 was present on smartphones at low, medium, and high emission, respectively. The vast majority of identified microorganisms came from human skin, mainly Staphylococci, together with Gram-negative and positive bacilli and yeasts. Moreover, the main isolated species and their mixture were exposed for 3 h to turned on and off smartphones to evaluate the effect of the electromagnetic wave emission on the bacterial cultivability, viability, morphology, and genotypic profile in respect to the unexposed broth cultures. A reduction rate of bacterial growth of 79 and 46% was observed in Staphylococcus aureus and Staphylococcus epidermidis broth cultures, respectively, in the presence of turned on smartphone. No differences in viability were observed in all detected conditions. Small colony variants and some differences in DNA fingerprinting were detected on bacteria when the smartphones were turned on in respect to the other conditions. The colonization of smartphones was limited to human skin microorganisms that can acquire phenotype and genotypic modifications when exposed to microwave emissions.}, } @article {pmid29247336, year = {2018}, author = {Roy, S and Nuckles, E and Archbold, DD}, title = {Effects of Phenolic Compounds on Growth of Colletotrichum spp. In Vitro.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {550-556}, pmid = {29247336}, issn = {1432-0991}, mesh = {Colletotrichum/*drug effects/*growth & development ; Fragaria/*chemistry/microbiology ; Fruit/chemistry/microbiology ; Phenols/chemistry/*pharmacology ; Plant Diseases/*microbiology ; Plant Extracts/chemistry/*pharmacology ; }, abstract = {Colletotrichum acutatum is responsible for anthracnose fruit rot, one of the most devastating diseases in strawberry. Phenolic compounds have been described as contributors to anthracnose resistance in strawberry (Fragaria x ananassa, Duch.). Six isolates of Colletotrichum acutatum and four isolates of three other Colletotrichum species, C. gloeosporioides, C. fragariae, and C. graminicola, associated with disease symptoms were investigated in this study. The potential inhibitory effect of phenolic acids (gallic acid, caffeic acid, chlorogenic acid, ferulic acid, trans-cinnamic acid, p-coumaric acid, salicylic acid), flavonoids (catechin, quercetin, naringenin), and ellagic acid, which are naturally found in strawberry, were screened against two different spore suspension concentrations of the Colletotrichum isolates at 5, 10, 50 mM in vitro. Among the phenolic acids and flavonoids tested in this study, only trans-cinnamic acid, ferulic acid, and p-coumaric acid inhibited fungal growth. The inhibitory effects were concentration-dependent but also varied with the spore suspension concentration of the isolates. The results demonstrated that trans-cinnamic acid had the greatest inhibitory effect on all Colletotrichum spp. isolates tested.}, } @article {pmid29247053, year = {2018}, author = {Robinson, JI and Baxter, EW and Owen, RL and Thomsen, M and Tomlinson, DC and Waterhouse, MP and Win, SJ and Nettleship, JE and Tiede, C and Foster, RJ and Owens, RJ and Fishwick, CWG and Harris, SA and Goldman, A and McPherson, MJ and Morgan, AW}, title = {Affimer proteins inhibit immune complex binding to FcγRIIIa with high specificity through competitive and allosteric modes of action.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E72-E81}, pmid = {29247053}, issn = {1091-6490}, support = {//Wellcome Trust/United Kingdom ; 19764//Arthritis Research UK/United Kingdom ; MR/K015346/1//Medical Research Council/United Kingdom ; MR/K018779/1//Medical Research Council/United Kingdom ; 094232/Z/10/Z//Wellcome Trust/United Kingdom ; //Department of Health/United Kingdom ; BB/M021610/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Allosteric Regulation ; Antigen-Antibody Complex/*chemistry/immunology ; Humans ; Immunoglobulin G/*chemistry/immunology ; *Molecular Dynamics Simulation ; Receptors, IgG/*chemistry/immunology ; }, abstract = {Protein-protein interactions are essential for the control of cellular functions and are critical for regulation of the immune system. One example is the binding of Fc regions of IgG to the Fc gamma receptors (FcγRs). High sequence identity (98%) between the genes encoding FcγRIIIa (expressed on macrophages and natural killer cells) and FcγRIIIb (expressed on neutrophils) has prevented the development of monospecific agents against these therapeutic targets. We now report the identification of FcγRIIIa-specific artificial binding proteins called "Affimer" that block IgG binding and abrogate FcγRIIIa-mediated downstream effector functions in macrophages, namely TNF release and phagocytosis. Cocrystal structures and molecular dynamics simulations have revealed the structural basis of this specificity for two Affimer proteins: One binds directly to the Fc binding site, whereas the other acts allosterically.}, } @article {pmid29247052, year = {2018}, author = {Ingebrigtsen, TS and Tanaka, H}, title = {Structural predictor for nonlinear sheared dynamics in simple glass-forming liquids.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {87-92}, pmid = {29247052}, issn = {1091-6490}, abstract = {Glass-forming liquids subjected to sufficiently strong shear universally exhibit striking nonlinear behavior; for example, a power-law decrease of the viscosity with increasing shear rate. This phenomenon has attracted considerable attention over the years from both fundamental and applicational viewpoints. However, the out-of-equilibrium and nonlinear nature of sheared fluids have made theoretical understanding of this phenomenon very challenging and thus slower to progress. We find here that the structural relaxation time as a function of the two-body excess entropy, calculated for the extensional axis of the shear flow, collapses onto the corresponding equilibrium curve for a wide range of pair potentials ranging from harsh repulsive to soft and finite. This two-body excess entropy collapse provides a powerful approach to predicting the dynamics of nonequilibrium liquids from their equilibrium counterparts. Furthermore, the two-body excess entropy scaling suggests that sheared dynamics is controlled purely by the liquid structure captured in the form of the two-body excess entropy along the extensional direction, shedding light on the perplexing mechanism behind shear thinning.}, } @article {pmid29246817, year = {2018}, author = {Jongsma, GFM and Barej, MF and Barratt, CD and Burger, M and Conradie, W and Ernst, R and Greenbaum, E and Hirschfeld, M and Leaché, AD and Penner, J and Portik, DM and Zassi-Boulou, AG and Rödel, MO and Blackburn, DC}, title = {Diversity and biogeography of frogs in the genus Amnirana (Anura: Ranidae) across sub-Saharan Africa.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {274-285}, doi = {10.1016/j.ympev.2017.12.006}, pmid = {29246817}, issn = {1095-9513}, mesh = {Africa South of the Sahara ; Amphibian Proteins/classification/genetics/metabolism ; Animals ; Anura/*classification/genetics ; *Biodiversity ; DNA/classification/isolation & purification/metabolism ; DNA, Mitochondrial/classification/isolation & purification/metabolism ; Evolution, Molecular ; Membrane Proteins/classification/genetics/metabolism ; *Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; }, abstract = {Frogs in the genus Amnirana (family Ranidae) are widely distributed across sub-Saharan Africa and present a model system for exploring the relationship between diversification and geography across the continent. Using multiple loci from the mitochondrial (16S) and nuclear genomes (DISP2, FICD, KIAA2013, REV3L), we generated a strongly supported species-level phylogeny that provides insights into the continental biogeography of African species of Amnirana, which form a monophyletic group within the genus. Species delimitation analyses suggest that there may be as many as seven additional species of Amnirana in Africa. The biogeographic history of Amnirana is marked by several dispersal and vicariance events, including dispersal from the Lower Guinean Forest into the Congo Basin. In addition, phylogeographic patterns within two widespread species, A. albolabris and A. galamensis, reveal undescribed cryptic diversity. Populations assigned to A. albolabris in western Africa are more closely related to A. fonensis and require recognition as a distinct species. Our analyses reveal that the Lower and Upper Guinean Forest regions served as important centers of interspecific and intraspecific diversifications for Amnirana.}, } @article {pmid29246816, year = {2018}, author = {Harris, RB and Alström, P and Ödeen, A and Leaché, AD}, title = {Discordance between genomic divergence and phenotypic variation in a rapidly evolving avian genus (Motacilla).}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {183-195}, doi = {10.1016/j.ympev.2017.11.020}, pmid = {29246816}, issn = {1095-9513}, support = {S10 RR029668/RR/NCRR NIH HHS/United States ; S10 RR027303/RR/NCRR NIH HHS/United States ; }, mesh = {Animals ; Cell Nucleus/genetics ; DNA/chemistry/isolation & purification/metabolism ; DNA, Mitochondrial/chemistry/classification/genetics ; *Genetic Variation ; Genotype ; Passeriformes/classification/*genetics ; Phenotype ; Phylogeny ; Polymorphism, Single Nucleotide ; Sequence Analysis, DNA ; }, abstract = {Generally, genotypes and phenotypes are expected to be spatially congruent; however, in widespread species complexes with few barriers to dispersal, multiple contact zones, and limited reproductive isolation, discordance between phenotypes and phylogeographic groups is more probable. Wagtails (Motacilla) are a genus of birds with striking plumage pattern variation across the Old World. Up to 13 subspecies are recognized within a single species, yet previous studies using mitochondrial DNA have supported polyphyletic phylogeographic groups that are inconsistent with subspecies plumage characteristics. In this study, we investigate the link between phenotypes and genotype by taking a phylogenetic approach. We use genome-wide SNPs, nuclear introns, and mitochondrial DNA to estimate population structure, isolation by distance, and species relationships. Together, our genetic sampling includes complete species-level sampling and comprehensive coverage of the three most phenotypically diverse Palearctic species. Our study provides strong evidence for species-level patterns of differentiation, however population-level differentiation is less pronounced. SNPs provide a robust estimate of species-level relationships, which are mostly corroborated by a combined analysis of mtDNA and nuclear introns (the first time-calibrated species tree for the genus). However, the mtDNA tree is strongly incongruent and is considered to misrepresent the species phylogeny. The extant wagtail lineages originated during the Pliocene and the Eurasian lineage underwent rapid diversification during the Pleistocene. Three of four widespread Eurasian species exhibit an east-west divide that contradicts both subspecies taxonomy and phenotypic variation. Indeed, SNPs fail to distinguish between phenotypically distinct subspecies within the M. alba and M. flava complexes, and instead support geographical regions, each of which is home to two or more different looking subspecies. This is a major step towards our understanding of wagtail phylogeny compared to previous analyses of fewer species and considerably less sequence data.}, } @article {pmid29246815, year = {2018}, author = {Caires, TA and de Mattos Lyra, G and Hentschke, GS and de Gusmão Pedrini, A and Sant'Anna, CL and de Castro Nunes, JM}, title = {Neolyngbya gen. nov. (Cyanobacteria, Oscillatoriaceae): A new filamentous benthic marine taxon widely distributed along the Brazilian coast.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {196-211}, doi = {10.1016/j.ympev.2017.12.009}, pmid = {29246815}, issn = {1095-9513}, mesh = {Biodiversity ; Brazil ; Cyanobacteria/*classification/genetics/ultrastructure ; DNA, Bacterial/chemistry/genetics/metabolism ; Microscopy, Electron, Transmission ; Phylogeny ; RNA, Ribosomal, 16S/chemistry/classification/genetics ; Sequence Analysis, DNA ; }, abstract = {Brazil has an extensive and environmentally diverse coastline, which favors the occurrence of numerous cyanobacterial morpho- and ecotypes. Nevertheless, this coastline is still poorly studied and its diversity is underestimated. Considering the family Oscillatoriaceae, Lyngbya deserves special attention. It includes many clades which are phylogenetically non-related but morphologically similar. Such clades occur in marine and freshwater environments and are traditionally treated as a single genus. In the current study, we sampled both mediolittoral and estuarine zones along the Brazilian coast. Based on a polyphasic characterization, we described a new genus of marine filamentous cyanobacteria: Neolyngbya. It includes six new species sampled in Brazil, which are described in this study (N. maris-brasilis, N. granulosa, N. irregularis, N. nodulosa, N. arenicola and N. tenuis). Additionally, the characterization included a Neolyngbya sp. from Japan in the clade, but only based on molecular data. All species presented irregular arrangement of thylakoids as described for Oscillatoriaceae. The new genus shares morphological characteristics with species in different clades of the Lyngbya complex. The ultrastructural analyses of Neolyngbya, however, showed numerous gas vesicles, especially in the interthylakoid space; such feature is not observed in benthic Lyngbya species. Neolyngbya formed a well-supported clade (16S rRNA phylogeny), however distantly related to L. aestuarii and L. confervoides, both marine species clusters. The Limnoraphis clade is in a sister relationship to the Neolyngbya clade, however the former occurs in freshwater plankton. Secondary structures of 16S-23S rRNA ITS sequences were congruent with the phylogeny. The polyphasic characterization was helpful to clarify the diversity and ecological aspects of benthic filamentous cyanobacteria and the evolutionary history of the group. This favors a better understanding of inter and infrageneric taxa. The number of novel taxa described in this study emphasizes the importance of conducting additional floristic surveys, mainly in underexplored marine environments, to reveal the real cyanobacterial biodiversity in these areas.}, } @article {pmid29244567, year = {2018}, author = {Watts, JC and Jones, TC and Herrig, A and Miller, M and Tenhumberg, B}, title = {Temporal Variation in Predation Risk May Explain Daily Rhythms of Foraging Behavior in an Orb-Weaving Spider.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {74-87}, doi = {10.1086/694775}, pmid = {29244567}, issn = {1537-5323}, mesh = {Animals ; Circadian Rhythm ; Female ; *Food Chain ; Models, Biological ; *Predatory Behavior ; Risk ; Spiders/*physiology ; Time Factors ; }, abstract = {Daily rhythms occur in numerous physiological and behavioral processes across an immense diversity of taxa, but there remain few cases in which mechanistic links between rhythms of trait expression and organismal fitness have been established. We construct a dynamic optimization model to determine whether risk allocation provides an adaptive explanation for the daily foraging rhythm observed in many species using the orb-weaving spider Cyclosa turbinata as a case study. Our model predicts that female C. turbinata should generally start foraging at lower levels of energy reserves (i.e., should be less bold) during midday when predators are most abundant. We also find that individuals' foraging efficacy determines whether daily rates of encounters with predators or prey more strongly influences boldness under high risk. The qualitative model predictions are robust to variation in our parameter estimates and likely apply to a wide range of taxa. The predictions are also consistent with observed patterns of foraging behavior under both laboratory and field conditions. We discuss the implications of our study for understanding the evolution of daily rhythms and the importance of model predictions for interpreting empirical studies and generating additional hypotheses regarding behavioral evolution.}, } @article {pmid29244566, year = {2018}, author = {Lehtonen, J}, title = {The Price Equation, Gradient Dynamics, and Continuous Trait Game Theory.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {146-153}, doi = {10.1086/694891}, pmid = {29244566}, issn = {1537-5323}, mesh = {*Biological Evolution ; *Game Theory ; *Genetic Fitness ; Models, Genetic ; }, abstract = {A recent article convincingly nominated the Price equation as the fundamental theorem of evolution and used it as a foundation to derive several other theorems. A major section of evolutionary theory that was not addressed is that of game theory and gradient dynamics of continuous traits with frequency-dependent fitness. Deriving fundamental results in these fields under the unifying framework of the Price equation illuminates similarities and differences between approaches and allows a simple, unified view of game-theoretical and dynamic concepts. Using Taylor polynomials and the Price equation, I derive a dynamic measure of evolutionary change, a condition for singular points, the convergence stability criterion, and an alternative interpretation of evolutionary stability. Furthermore, by applying the Price equation to a multivariable Taylor polynomial, the direct fitness approach to kin selection emerges. Finally, I compare these results to the mean gradient equation of quantitative genetics and the canonical equation of adaptive dynamics.}, } @article {pmid29244565, year = {2018}, author = {Levitan, DR}, title = {Do Sperm Really Compete and Do Eggs Ever Have a Choice? Adult Distribution and Gamete Mixing Influence Sexual Selection, Sexual Conflict, and the Evolution of Gamete Recognition Proteins in the Sea.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {88-105}, doi = {10.1086/694780}, pmid = {29244565}, issn = {1537-5323}, mesh = {Animals ; Biological Evolution ; *Evolution, Molecular ; Female ; Male ; *Mating Preference, Animal ; Models, Biological ; Ovum/physiology ; *Sperm-Ovum Interactions ; Spermatozoa/physiology ; Strongylocentrotus/*physiology ; }, abstract = {The evolution of gametic compatibility and the effectiveness of compatibility, within and across species, depend on whether sperm from different males directly compete for an egg and whether eggs ever have a choice. Direct sperm competition and egg choice depend on whether sperm from different males arrive at an egg in the brief interval between first sperm contact and fertilization. Although this process may be relevant for all sexually reproducing organisms, it is most easily examined in aquatic external fertilizers. When sperm are released into the sea, packets of seawater at the spatial scale relevant to single eggs might contain sperm from only one male, eliminating the potential for direct sperm competition and egg choice. Field experiments and a simple heuristic model examining the degree of sperm mixing for the sea urchin Strongylocentrotus franciscanus indicate that degree of competitive fertilization depends on density and distribution of competing males and that the nature of this competition influences whether males with high- or low-affinity gamete recognition protein genotypes have higher reproductive success. These results provide a potential explanation for the generation and maintenance of variation in gamete recognition proteins and why effectiveness of conspecific sperm precedence can be density dependent.}, } @article {pmid29244564, year = {2018}, author = {}, title = {2017 American Society of Naturalists Awards.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {vi-viii}, doi = {10.1086/694904}, pmid = {29244564}, issn = {1537-5323}, mesh = {*Awards and Prizes ; Ecology/*history ; Genetics/*history ; History, 20th Century ; History, 21st Century ; Societies, Scientific ; United States ; }, } @article {pmid29244563, year = {2018}, author = {Wiernasz, DC and Cole, BJ}, title = {Offspring Size and Reproductive Allocation in Harvester Ants.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {120-134}, doi = {10.1086/694903}, pmid = {29244563}, issn = {1537-5323}, mesh = {Animals ; Ants/genetics/*physiology ; Body Size ; Colorado ; Diet ; Female ; *Genetic Fitness ; Male ; Models, Biological ; Population Growth ; Reproduction ; Sex Factors ; }, abstract = {A fundamental decision that an organism must make is how to allocate resources to offspring, with respect to both size and number. The two major theoretical approaches to this problem, optimal offspring size and optimistic brood size models, make different predictions that may be reconciled by including how offspring fitness is related to size. We extended the reasoning of Trivers and Willard (1973) to derive a general model of how parents should allocate additional resources with respect to the number of males and females produced, and among individuals of each sex, based on the fitness payoffs of each. We then predicted how harvester ant colonies should invest additional resources and tested three hypotheses derived from our model, using data from 3 years of food supplementation bracketed by 6 years without food addition. All major results were predicted by our model: food supplementation increased the number of reproductives produced. Male, but not female, size increased with food addition; the greatest increases in male size occurred in colonies that made small females. We discuss how use of a fitness landscape improves quantitative predictions about allocation decisions. When parents can invest differentially in offspring of different types, the best strategy will depend on parental state as well as the effect of investment on offspring fitness.}, } @article {pmid29244562, year = {2018}, author = {Dridi, S and Akçay, E}, title = {Learning to Cooperate: The Evolution of Social Rewards in Repeated Interactions.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {58-73}, doi = {10.1086/694822}, pmid = {29244562}, issn = {1537-5323}, mesh = {Animals ; *Biological Evolution ; *Cooperative Behavior ; Game Theory ; Humans ; *Learning ; Models, Biological ; Prisoner Dilemma ; *Reward ; *Social Behavior ; }, abstract = {Understanding the behavioral and psychological mechanisms underlying social behaviors is one of the major goals of social evolutionary theory. In particular, a persistent question about animal cooperation is to what extent it is supported by other-regarding preferences-the motivation to increase the welfare of others. In many situations, animals adjust their behaviors through learning by responding to the rewards they experience as a consequence of their actions. Therefore, we may ask whether learning in social situations can be driven by evolved other-regarding rewards. Here we develop a mathematical model in order to ask whether the mere act of cooperating with a social partner will evolve to be inherently rewarding. Individuals interact repeatedly in pairs and adjust their behaviors through reinforcement learning. We assume that individuals associate with each game outcome an internal reward value. These perceived rewards are genetically evolving traits. We find that conditionally cooperative rewards that value mutual cooperation positively but the sucker's outcome negatively tend to be evolutionarily stable. Purely other-regarding rewards can evolve only under special parameter combinations. On the other hand, selfish rewards that always lead to pure defection are also evolutionarily successful. These findings are consistent with empirical observations showing that humans tend to display conditionally cooperative behavior and also exhibit a diversity of preferences. Our model also demonstrates the need to further integrate multiple levels of biological causation of behavior.}, } @article {pmid29244561, year = {2018}, author = {Kopp, M and Servedio, MR and Mendelson, TC and Safran, RJ and Rodríguez, RL and Hauber, ME and Scordato, EC and Symes, LB and Balakrishnan, CN and Zonana, DM and van Doorn, GS}, title = {Mechanisms of Assortative Mating in Speciation with Gene Flow: Connecting Theory and Empirical Research.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {1-20}, doi = {10.1086/694889}, pmid = {29244561}, issn = {1537-5323}, mesh = {Animals ; Biological Evolution ; *Gene Flow ; *Genetic Speciation ; *Mating Preference, Animal ; Models, Genetic ; *Phenotype ; }, abstract = {The large body of theory on speciation with gene flow has brought to light fundamental differences in the effects of two types of mating rules on speciation: preference/trait rules, in which divergence in both (female) preferences and (male) mating traits is necessary for assortment, and matching rules, in which individuals mate with like individuals on the basis of the presence of traits or alleles that they have in common. These rules can emerge from a variety of behavioral or other mechanisms in ways that are not always obvious. We discuss the theoretical properties of both types of rules and explain why speciation is generally thought to be more likely under matching rather than preference/trait rules. We furthermore discuss whether specific assortative mating mechanisms fall under a preference/trait or matching rule, present empirical evidence for these mechanisms, and propose empirical tests that could distinguish between them. The synthesis of the theoretical literature on these assortative mating rules with empirical studies of the mechanisms by which they act can provide important insights into the occurrence of speciation with gene flow. Finally, by providing a clear framework we hope to inspire greater alignment in the ways that both theoreticians and empiricists study mating rules and how these rules affect speciation through maintaining or eroding barriers to gene flow among closely related species or populations.}, } @article {pmid29244560, year = {2018}, author = {Plard, F and Schindler, S and Arlettaz, R and Schaub, M}, title = {Sex-Specific Heterogeneity in Fixed Morphological Traits Influences Individual Fitness in a Monogamous Bird Population.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {106-119}, doi = {10.1086/694823}, pmid = {29244560}, issn = {1537-5323}, mesh = {Age Factors ; Animals ; Birds/*anatomy & histology/genetics/*physiology ; Female ; *Genetic Fitness ; *Longevity ; Male ; Phenotype ; Population Dynamics ; *Reproduction ; Sex Characteristics ; Switzerland ; }, abstract = {Theoretical work has emphasized the important role of individual traits on population dynamics, but empirical models are often based on average or stage-dependent demographic rates. In this study on a monogamous bird, the Eurasian hoopoe (Upupa epops), we show how the interactions between male and female fixed and dynamic heterogeneity influence demographic rates and population dynamics. We built an integral projection model including individual sex, age, condition (reflecting dynamic heterogeneity), and fixed morphology (reflecting fixed heterogeneity). Fixed morphology was derived from a principal component analysis of six morphological traits. Our results revealed that reproductive success and survival were linked to fixed heterogeneity, whereas dynamic heterogeneity influenced mainly the timing of reproduction. Fixed heterogeneity had major consequences for the population growth rate, but interestingly, its effect on population dynamics differed between the sexes. Female fixed morphology was directly linked to annual reproductive success, whereas male fixed morphology also influenced annual survival, being twice higher in large than in small males. Even in a monogamous bird with shared parental care, large males can reach 10% higher fitness than females. Including the dynamics of male and female individual traits in population models refines our understanding of the individual mechanisms that influence demographic rates and population dynamics and can help in identifying differences in sex-specific strategies.}, } @article {pmid29244559, year = {2018}, author = {Muñoz, MM and Losos, JB}, title = {Thermoregulatory Behavior Simultaneously Promotes and Forestalls Evolution in a Tropical Lizard.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {E15-E26}, doi = {10.1086/694779}, pmid = {29244559}, issn = {1537-5323}, mesh = {Adaptation, Biological ; Altitude ; Animals ; *Behavior, Animal ; *Biological Evolution ; *Body Temperature Regulation ; Dominican Republic ; *Ecosystem ; Lizards/anatomy & histology/*physiology ; Microclimate ; }, abstract = {The role of behavior in evolution has long been discussed, with some arguing that behavior promotes evolution by exposing organisms to selection (behavioral drive) and others proposing that it inhibits evolution by shielding organisms from environmental variation (behavioral inertia). However, this discussion has generally focused on the effects of behavior along a single axis without considering that behavior simultaneously influences selection in various niche dimensions. By examining evolutionary change along two distinct niche axes-structural and thermal-we propose that behavior simultaneously drives and impedes evolution in a group of Anolis lizards from the Caribbean island of Hispaniola. Specifically, a behavioral shift in microhabitat to boulders at high altitude enables thermoregulation, thus forestalling physiological evolution in spite of colder environments. This same behavioral shift drives skull and limb evolution to boulder use. Our results emphasize the multidimensional effects of behavior in evolution. These findings reveal how, rather than being diametrically opposed, niche conservatism and niche lability can occur simultaneously. Furthermore, patterns of niche evolution may vary at different geographic scales: because of thermoregulatory behavior, lizards at high and low elevation share similar microclimatic niches (consistent with niche conservatism) while inhabiting distinct macroclimatic environments (consistent with niche divergence). Together, our results suggest that behavior can connect patterns of niche divergence and conservatism at different geographic scales and among traits.}, } @article {pmid29244558, year = {2018}, author = {Twyford, AD and Caola, AM and Choudhary, P and Raina, R and Friedman, J}, title = {Loss of Color Pigmentation Is Maintained at High Frequency in a Monkey Flower Population.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {135-145}, doi = {10.1086/694853}, pmid = {29244558}, issn = {1537-5323}, mesh = {Anthocyanins/*metabolism ; California ; Color ; *Gene Frequency ; *Genetic Fitness ; Genetic Variation ; Mimulus/genetics/*physiology ; Phenotype ; Pigmentation/genetics ; }, abstract = {Color polymorphisms have long been of evolutionary interest for their diverse roles, including mate choice, predator avoidance, and pollinator attraction. While color variation is often under strong selection, some taxa demonstrate unexpectedly high frequencies of presumed deleterious color forms. Here we show that a genetic variant underlying complete loss of anthocyanin pigmentation has risen to an unexpectedly high frequency of >0.2 in a natural population of the plant Mimulus guttatus. Decreased expression of MYB5 transcription factor is associated with unpigmented morphs. While the allele was found only in heterozygote adults in the wild, suggesting negative selection, experiments were unable to demonstrate a fitness cost for unpigmented plants, suggesting a cryptic selection pressure in the wild. However, life-history differences among morphs suggests that unpigmented individuals benefit from later flowering and clonal growth. Overall, our study highlights the complex interplay of factors maintaining variation in nature, even for genes of major effect.}, } @article {pmid29244557, year = {2018}, author = {Chen, N and Jayaprakash, C and Yu, K and Guttal, V}, title = {Rising Variability, Not Slowing Down, as a Leading Indicator of a Stochastically Driven Abrupt Transition in a Dryland Ecosystem.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {E1-E14}, doi = {10.1086/694821}, pmid = {29244557}, issn = {1537-5323}, mesh = {China ; *Conservation of Natural Resources ; *Desert Climate ; *Ecosystem ; Grassland ; Models, Biological ; Stochastic Processes ; }, abstract = {Complex systems can undergo abrupt state transitions near critical points. Theory and controlled experimental studies suggest that the approach to critical points can be anticipated by critical slowing down (CSD), that is, a characteristic slowdown in the dynamics. The validity of this indicator in field ecosystems, where stochasticity is important in driving transitions, remains unclear. We analyze long-term data from a dryland ecosystem in the Shapotou region of China and show that the ecosystem underwent an abrupt transition from a nearly bare to a moderate grass cover state. Prior to the transition, the system showed no (or weak) signatures of CSD but exhibited expected increasing trends in the variability of the grass cover, quantified by variance and skewness. These surprising results are consistent with the theoretical expectation of stochastically driven abrupt transitions that occur away from critical points; indeed, a driver of vegetation-annual rainfall-showed rising variance prior to the transition. Our study suggests that rising variability can potentially serve as a leading indicator of stochastically driven transitions in real-world ecosystems.}, } @article {pmid29244556, year = {2018}, author = {Pope, NS and Jha, S}, title = {Seasonal Food Scarcity Prompts Long-Distance Foraging by a Wild Social Bee.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {45-57}, doi = {10.1086/694843}, pmid = {29244556}, issn = {1537-5323}, mesh = {Animals ; Bayes Theorem ; Bees/genetics/*physiology ; California ; Feeding Behavior ; Flowers ; *Pollination ; Seasons ; }, abstract = {Foraging is an essential process for mobile animals, and its optimization serves as a foundational theory in ecology and evolution; however, drivers of foraging are rarely investigated across landscapes and seasons. Using a common bumblebee species from the western United States (Bombus vosnesenskii), we ask whether seasonal decreases in food resources prompt changes in foraging behavior and space use. We employ a unique integration of population genetic tools and spatially explicit foraging models to estimate foraging distances and rates of patch visitation for wild bumblebee colonies across three study regions and two seasons. By mapping the locations of 669 wild-caught individual foragers, we find substantial variation in colony-level foraging distances, often exhibiting a 60-fold difference within a study region. Our analysis of visitation rates indicates that foragers display a preference for destination patches with high floral cover and forage significantly farther for these patches, but only in the summer, when landscape-level resources are low. Overall, these results indicate that an increasing proportion of long-distance foraging bouts take place in the summer. Because wild bees are pollinators, their foraging dynamics are of urgent concern, given the potential impacts of global change on their movement and services. The behavioral shift toward long-distance foraging with seasonal declines in food resources suggests a novel, phenologically directed approach to landscape-level pollinator conservation and greater consideration of late-season floral resources in pollinator habitat management.}, } @article {pmid29244555, year = {2018}, author = {Lion, S}, title = {Theoretical Approaches in Evolutionary Ecology: Environmental Feedback as a Unifying Perspective.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {21-44}, doi = {10.1086/694865}, pmid = {29244555}, issn = {1537-5323}, mesh = {Adaptation, Biological ; *Biological Evolution ; Ecology/*methods ; Feedback ; *Game Theory ; Gene Frequency ; Genetic Fitness ; *Models, Genetic ; }, abstract = {Evolutionary biology and ecology have a strong theoretical underpinning, and this has fostered a variety of modeling approaches. A major challenge of this theoretical work has been to unravel the tangled feedback loop between ecology and evolution. This has prompted the development of two main classes of models. While quantitative genetics models jointly consider the ecological and evolutionary dynamics of a focal population, a separation of timescales between ecology and evolution is assumed by evolutionary game theory, adaptive dynamics, and inclusive fitness theory. As a result, theoretical evolutionary ecology tends to be divided among different schools of thought, with different toolboxes and motivations. My aim in this synthesis is to highlight the connections between these different approaches and clarify the current state of theory in evolutionary ecology. Central to this approach is to make explicit the dependence on environmental dynamics of the population and evolutionary dynamics, thereby materializing the eco-evolutionary feedback loop. This perspective sheds light on the interplay between environmental feedback and the timescales of ecological and evolutionary processes. I conclude by discussing some potential extensions and challenges to our current theoretical understanding of eco-evolutionary dynamics.}, } @article {pmid29244554, year = {2018}, author = {Bolnick, DI}, title = {Letter from the Editor.}, journal = {The American naturalist}, volume = {191}, number = {1}, pages = {iii-v}, doi = {10.1086/694918}, pmid = {29244554}, issn = {1537-5323}, mesh = {*Ecology ; *Editorial Policies ; *Ethology ; *Periodicals as Topic ; }, } @article {pmid29243890, year = {2018}, author = {Strelin, MM and Benitez-Vieyra, S and Fornoni, J and Klingenberg, CP and Cocucci, A}, title = {The evolution of floral ontogenetic allometry in the Andean genus Caiophora (Loasaceae, subfam. Loasoideae).}, journal = {Evolution & development}, volume = {20}, number = {1}, pages = {29-39}, doi = {10.1111/ede.12246}, pmid = {29243890}, issn = {1525-142X}, mesh = {Animals ; Bees/*physiology ; *Biological Evolution ; Flowers/*anatomy & histology/*physiology ; Organ Size ; Phylogeny ; Pollination ; }, abstract = {The astounding variety of angiosperm flower morphologies has evolved in response to many selective forces. Flower development is highly coordinated and involves developmental associations between size and shape, ontogenetic allometry, which in turn affect the morphology of mature flowers. Although ontogenetic allometries can act as a developmental constraint and may influence adaptive evolution, allometries can evolve themselves and may change rapidly in response to selection. We explored the evolution of ontogenetic allometry in the flowers of 11 species of Loasoideae. Seven species belong to Caiophora, which radiated recently in the central Andes, and contains species that are pollinated by bees, hummingbirds, and small rodents. According to a previous study, the diversification of Caiophora involved departures from simple allometric scaling, but the changes to allometry that enabled flower diversification have not been explored yet. We characterized the ontogenetic allometry of each species with the methods of geometric morphometrics. We studied the evolution of allometries by constructing allometric spaces, in which the allometry of each species is represented by a point and the arrangement of points indicates the relations among allometric trajectories. To examine the history of changes of ontogenetic allometries, we projected the phylogeny into the allometric spaces. Inspection of allometric spaces suggests that ontogenetic variation is limited to a few dominant features. The allometries of the two main functional flower parts under study differ in their evolutionary labilities, and patterns of variation reflect pollination systems, differences in structural organization, and abiotic environmental factors.}, } @article {pmid29243871, year = {2018}, author = {Redl, E and Scherholz, M and Wollesen, T and Todt, C and Wanninger, A}, title = {Expression of six3 and otx in Solenogastres (Mollusca) supports an ancestral role in bilaterian anterior-posterior axis patterning.}, journal = {Evolution & development}, volume = {20}, number = {1}, pages = {17-28}, pmid = {29243871}, issn = {1525-142X}, mesh = {Animals ; Biological Evolution ; Body Patterning ; Brain/anatomy & histology/embryology/metabolism ; Eye Proteins/*genetics ; Gene Expression Regulation, Developmental ; Head/anatomy & histology/embryology ; Homeodomain Proteins/*genetics ; Mollusca/*anatomy & histology/embryology/*genetics/physiology ; Nerve Tissue Proteins/*genetics ; Otx Transcription Factors/*genetics ; }, abstract = {The homeodomain transcription factors six3 and otx are involved in patterning the anterior body and parts of the central nervous system (CNS) in bilaterians. Their similar expression patterns have been used as an argument for homology of heads, brains, segmentation, and ciliated larvae. We investigated the developmental expression of six3 and otx in the aplacophoran mollusk Wirenia argentea. Six3 is expressed in subepithelial cells delimiting the apical organ of the solenogaster pericalymma larva. Otx is expressed in cells of the prototroch and adjacent regions as well as in posterior extensions of the prototrochal expression domain. Advanced larvae also show pretrochal otx expression in the developing CNS. Comparative analysis of six3 and otx expression in bilaterians argues for an ancestral function in anterior-posterior body axis patterning but, due to its presence in animals lacking a head and/or a brain, not necessarily for the presence of these morphological structures in the last common ancestor (LCA) of bilaterians. Likewise, the hypothesis that the posterior border of otx expression corresponds to the border between the unsegmented head and the segmented trunk of the LCA of protostomes is not supported, since otx is extensively expressed in the trunk in W. argentea and numerous other protostomes.}, } @article {pmid29243391, year = {2018}, author = {Bromham, L and Duchêne, S and Hua, X and Ritchie, AM and Duchêne, DA and Ho, SYW}, title = {Bayesian molecular dating: opening up the black box.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1165-1191}, doi = {10.1111/brv.12390}, pmid = {29243391}, issn = {1469-185X}, abstract = {Molecular dating analyses allow evolutionary timescales to be estimated from genetic data, offering an unprecedented capacity for investigating the evolutionary past of all species. These methods require us to make assumptions about the relationship between genetic change and evolutionary time, often referred to as a 'molecular clock'. Although initially regarded with scepticism, molecular dating has now been adopted in many areas of biology. This broad uptake has been due partly to the development of Bayesian methods that allow complex aspects of molecular evolution, such as variation in rates of change across lineages, to be taken into account. But in order to do this, Bayesian dating methods rely on a range of assumptions about the evolutionary process, which vary in their degree of biological realism and empirical support. These assumptions can have substantial impacts on the estimates produced by molecular dating analyses. The aim of this review is to open the 'black box' of Bayesian molecular dating and have a look at the machinery inside. We explain the components of these dating methods, the important decisions that researchers must make in their analyses, and the factors that need to be considered when interpreting results. We illustrate the effects that the choices of different models and priors can have on the outcome of the analysis, and suggest ways to explore these impacts. We describe some major research directions that may improve the reliability of Bayesian dating. The goal of our review is to help researchers to make informed choices when using Bayesian phylogenetic methods to estimate evolutionary rates and timescales.}, } @article {pmid29243069, year = {2018}, author = {Zhang, XG and Liu, JW and Tang, P and Liu, ZY and Guo, GJ and Sun, QY and Yin, JJ}, title = {Identification of a New Uncompetitive Inhibitor of Adenosine Deaminase from Endophyte Aspergillus niger sp.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {565-573}, pmid = {29243069}, issn = {1432-0991}, support = {31360379//National Natural Science Foundation of China/ ; 17JR5RA128//Gansu province natural science fund/ ; }, mesh = {Adenosine Deaminase/chemistry/metabolism ; Adenosine Deaminase Inhibitors/*chemistry/metabolism ; Aspergillus niger/*chemistry/genetics/isolation & purification/metabolism ; Cell Line ; Endophytes/*chemistry/genetics/isolation & purification/metabolism ; Humans ; Magnetic Resonance Spectroscopy ; Molecular Structure ; Plants/*microbiology ; }, abstract = {Adenosine deaminase (ADA) is an enzyme widely distributed from bacteria to humans. ADA is known as a potential therapeutic target for the treatment of lymphoproliferative disorders and cancer. Endophytes are endosymbionts, often bacteria or fungi, which live within plant tissues and internal organs or intercellular space. Endophytes have a broad variety of bioactive metabolites that are used for the identification of novel natural compounds. Here, 54 morphologically distinct endophyte strains were isolated from six plants such as Peganum harmala Linn., Rheum officinale Baill., Gentiana macrophylla Pall., Radix stephaniae tetrandrae, Myrrha, and Equisetum hyemale Linn. The isolated strains were used for the search of ADA inhibitors that resulted in the identification of the strain with the highest inhibition activity, Aspergillus niger sp. Four compounds were isolated from this strain using three-step chromatography procedure, and compound 2 was determined as the compound with the highest inhibition activity of ADA. Based on the results of 1H and 13C NMR spectroscopies, compound 2 was identified as 3-(4-nitrophenyl)-5-phenyl isoxazole. We showed that compound 2 was a new uncompetitive inhibitor of ADA with high cytotoxic effect on HepG2 and SMCC-7721 cells (the IC50 values were 0.347 and 0.380 mM, respectively). These results suggest that endophyte strains serve as promising sources for the identification of ADA inhibitors, and compound 2 could be an effective drug in the cancer treatment.}, } @article {pmid29242587, year = {2018}, author = {}, title = {Our first year by the numbers.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {1-2}, doi = {10.1038/s41559-017-0440-z}, pmid = {29242587}, issn = {2397-334X}, } @article {pmid29242586, year = {2018}, author = {Barnett, R and Lorenzen, E}, title = {Thylacine tales.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {7-8}, doi = {10.1038/s41559-017-0384-3}, pmid = {29242586}, issn = {2397-334X}, } @article {pmid29242585, year = {2018}, author = {Vanbergen, AJ and Espíndola, A and Aizen, MA}, title = {Risks to pollinators and pollination from invasive alien species.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {16-25}, doi = {10.1038/s41559-017-0412-3}, pmid = {29242585}, issn = {2397-334X}, mesh = {Animals ; *Bees ; Biodiversity ; Biological Evolution ; *Diptera ; Ecosystem ; *Introduced Species ; *Pollination ; Risk ; }, abstract = {Invasive alien species modify pollinator biodiversity and the services they provide that underpin ecosystem function and human well-being. Building on the Intergovernmental Science-Policy Platform for Biodiversity and Ecosystem Services (IPBES) global assessment of pollinators and pollination, we synthesize current understanding of invasive alien impacts on pollinators and pollination. Invasive alien species create risks and opportunities for pollinator nutrition, re-organize species interactions to affect native pollination and community stability, and spread and select for virulent diseases. Risks are complex but substantial, and depend greatly on the ecological function and evolutionary history of both the invader and the recipient ecosystem. We highlight evolutionary implications for pollination from invasive alien species, and identify future research directions, key messages and options for decision-making.}, } @article {pmid29242579, year = {2018}, author = {Ramirez, KS and Berhe, AA and Burt, J and Gil-Romera, G and Johnson, RF and Koltz, AM and Lacher, I and McGlynn, T and Nielsen, KJ and Schmidt, R and Simonis, JL and terHorst, CP and Tuff, K}, title = {The future of ecology is collaborative, inclusive and deconstructs biases.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {200}, doi = {10.1038/s41559-017-0445-7}, pmid = {29242579}, issn = {2397-334X}, } @article {pmid29242578, year = {2018}, author = {Baum, JK and Martin, TG}, title = {It is time to overcome unconscious bias in ecology.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {201}, doi = {10.1038/s41559-017-0441-y}, pmid = {29242578}, issn = {2397-334X}, } @article {pmid29242577, year = {2018}, author = {Bruna, EM}, title = {Editorial board members are a non-random sample of ecological experts.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {202}, doi = {10.1038/s41559-017-0443-9}, pmid = {29242577}, issn = {2397-334X}, } @article {pmid29242576, year = {2018}, author = {Gilbert, GS}, title = {Can 100 must-read papers also reflect 'who' is ecology?.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {203}, doi = {10.1038/s41559-017-0444-8}, pmid = {29242576}, issn = {2397-334X}, } @article {pmid29242235, year = {2018}, author = {Yanagisawa, Y and Nan, Y and Okuro, K and Aida, T}, title = {Mechanically robust, readily repairable polymers via tailored noncovalent cross-linking.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {72-76}, doi = {10.1126/science.aam7588}, pmid = {29242235}, issn = {1095-9203}, abstract = {Expanding the range of healable materials is an important challenge for sustainable societies. Noncrystalline, high-molecular-weight polymers generally form mechanically robust materials, which, however, are difficult to repair once they are fractured. This is because their polymer chains are heavily entangled and diffuse too sluggishly to unite fractured surfaces within reasonable time scales. Here we report that low-molecular-weight polymers, when cross-linked by dense hydrogen bonds, yield mechanically robust yet readily repairable materials, despite their extremely slow diffusion dynamics. A key was to use thiourea, which anomalously forms a zigzag hydrogen-bonded array that does not induce unfavorable crystallization. Another key was to incorporate a structural element for activating the exchange of hydrogen-bonded pairs, which enables the fractured portions to rejoin readily upon compression.}, } @article {pmid29242233, year = {2018}, author = {Cabrera, CR and Tanzi, L and Sanz, J and Naylor, B and Thomas, P and Cheiney, P and Tarruell, L}, title = {Quantum liquid droplets in a mixture of Bose-Einstein condensates.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6373}, pages = {301-304}, doi = {10.1126/science.aao5686}, pmid = {29242233}, issn = {1095-9203}, abstract = {Quantum droplets are small clusters of atoms self-bound by the balance of attractive and repulsive forces. Here, we report on the observation of droplets solely stabilized by contact interactions in a mixture of two Bose-Einstein condensates. We demonstrate that they are several orders of magnitude more dilute than liquid helium by directly measuring their size and density via in situ imaging. We show that the droplets are stablized against collapse by quantum fluctuations and that they require a minimum atom number to be stable. Below that number, quantum pressure drives a liquid-to-gas transition that we map out as a function of interaction strength. These ultradilute isotropic liquids remain weakly interacting and constitute an ideal platform to benchmark quantum many-body theories.}, } @article {pmid29242231, year = {2018}, author = {Guna, A and Volkmar, N and Christianson, JC and Hegde, RS}, title = {The ER membrane protein complex is a transmembrane domain insertase.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {470-473}, pmid = {29242231}, issn = {1095-9203}, support = {MC_UP_A022_1007//Medical Research Council/United Kingdom ; MR/L001209/1//Medical Research Council/United Kingdom ; }, mesh = {Calmodulin/chemistry/metabolism ; Cytosol/metabolism ; Endoplasmic Reticulum/chemistry/*metabolism ; HEK293 Cells ; Humans ; Intracellular Membranes/chemistry/*metabolism ; Membrane Proteins/chemistry/*metabolism ; Protein Domains ; Protein Transport ; }, abstract = {Insertion of proteins into membranes is an essential cellular process. The extensive biophysical and topological diversity of membrane proteins necessitates multiple insertion pathways that remain incompletely defined. Here we found that known membrane insertion pathways fail to effectively engage tail-anchored membrane proteins with moderately hydrophobic transmembrane domains. These proteins are instead shielded in the cytosol by calmodulin. Dynamic release from calmodulin allowed sampling of the endoplasmic reticulum (ER), where the conserved ER membrane protein complex (EMC) was shown to be essential for efficient insertion in vitro and in cells. Purified EMC in synthetic liposomes catalyzed the insertion of its substrates in a reconstituted system. Thus, EMC is a transmembrane domain insertase, a function that may explain its widely pleiotropic membrane-associated phenotypes across organisms.}, } @article {pmid29242213, year = {2018}, author = {Sosa, OA}, title = {Phosphorus redox reactions as pinch hitters in microbial metabolism.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {7-8}, pmid = {29242213}, issn = {1091-6490}, mesh = {*Oxidation-Reduction ; *Phosphorus ; }, } @article {pmid29242212, year = {2018}, author = {Martin, RJ}, title = {Nuclear option prevents hyperinfection in the Strongyloides worm war.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {9-11}, pmid = {29242212}, issn = {1091-6490}, support = {R01 AI047194/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; *Strongyloides ; *Strongyloidiasis ; }, } @article {pmid29242166, year = {2018}, author = {Campillo, LC and Oliveros, CH and Sheldon, FH and Moyle, RG}, title = {Genomic data resolve gene tree discordance in spiderhunters (Nectariniidae, Arachnothera).}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {151-157}, doi = {10.1016/j.ympev.2017.12.011}, pmid = {29242166}, issn = {1095-9513}, mesh = {Animals ; Biological Evolution ; Computational Biology ; DNA/chemistry/isolation & purification/metabolism ; Genetic Loci ; *Genome ; Likelihood Functions ; Passeriformes/*classification/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Reduced representation genomic sequencing methods efficiently gather sequence data from thousands of loci throughout the genome. These data can be used to test previous phylogenetic hypotheses produced from limited numbers of mitochondrial and nuclear loci that often reveal intriguing, but conflicting, results. In this paper, we use phylogenomic data to revisit recent molecular phylogenetic work that clarified many taxonomic relationships within spiderhunters, but also questioned the monophyly of this distinctive genus of sunbirds (AVES: Nectariniidae; Arachnothera). DNA sequence data were produced by target-capture sequencing of ultraconserved elements (UCEs) to infer the evolutionary history of 11 species of Arachnothera and six outgroups, including the Purple-naped Sunbird (Hypogramma hypogrammicum), which previous work suggested might lie within Arachnothera. Although we recovered many different gene tree topologies, concatenated and coalescent methods of analysis converged on a species tree that strongly supports the monophyly of Arachnothera, with Hypogramma as its sister taxon.}, } @article {pmid29242165, year = {2018}, author = {Thomson, RC and Spinks, PQ and Shaffer, HB}, title = {Molecular phylogeny and divergence of the map turtles (Emydidae: Graptemys).}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {61-70}, doi = {10.1016/j.ympev.2017.11.012}, pmid = {29242165}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Genetic Variation ; Geography ; *Phylogeny ; Species Specificity ; Time Factors ; Turtles/*classification/*genetics ; }, abstract = {The map turtles (genus Graptemys) comprise a morphologically diverse clade that forms a major component of the southeastern US hotspot of chelonian diversity. Map turtles have experienced both recent and rapid diversification resulting in long-standing uncertainty regarding species boundaries and phylogenetic relationships within the genus as well as timing of their divergence. We present a phylogeny for the group that includes geographically representative sampling for all described species and subspecies. We make use of an empirical prior on rates of molecular evolution to estimate divergence times with a molecular clock under a coalescent framework. Together, the phylogeny and divergence time estimates suggest that diversification has been both more recent and more rapid than has so far been suspected. We provide a well-supported evolutionary framework for Graptemys that is necessary for understanding map turtle diversity, biogeography, and for conservation of this threatened clade of turtles.}, } @article {pmid29242164, year = {2018}, author = {Dauphin, B and Grant, JR and Farrar, DR and Rothfels, CJ}, title = {Rapid allopolyploid radiation of moonwort ferns (Botrychium; Ophioglossaceae) revealed by PacBio sequencing of homologous and homeologous nuclear regions.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {342-353}, doi = {10.1016/j.ympev.2017.11.025}, pmid = {29242164}, issn = {1095-9513}, mesh = {Bayes Theorem ; Cell Nucleus/genetics ; Computational Biology ; Cryptochromes/chemistry/classification/genetics ; DNA, Plant/chemistry/isolation & purification/metabolism ; Ferns/*classification/genetics ; Phylogeny ; Polyploidy ; Sequence Analysis, DNA ; }, abstract = {Polyploidy is a major speciation process in vascular plants, and is postulated to be particularly important in shaping the diversity of extant ferns. However, limitations in the availability of bi-parental markers for ferns have greatly limited phylogenetic investigation of polyploidy in this group. With a large number of allopolyploid species, the genus Botrychium is a classic example in ferns where recurrent polyploidy is postulated to have driven frequent speciation events. Here, we use PacBio sequencing and the PURC bioinformatics pipeline to capture all homeologous or allelic copies of four long (∼1 kb) low-copy nuclear regions from a sample of 45 specimens (25 diploids and 20 polyploids) representing 37 Botrychium taxa, and three outgroups. This sample includes most currently recognized Botrychium species in Europe and North America, and the majority of our specimens were genotyped with co-dominant nuclear allozymes to ensure species identification. We analyzed the sequence data using maximum likelihood (ML) and Bayesian inference (BI) concatenated-data ("gene tree") approaches to explore the relationships among Botrychium species. Finally, we estimated divergence times among Botrychium lineages and inferred the multi-labeled polyploid species tree showing the origins of the polyploid taxa, and their relationships to each other and to their diploid progenitors. We found strong support for the monophyly of the major lineages within Botrychium and identified most of the parental donors of the polyploids; these results largely corroborate earlier morphological and allozyme-based investigations. Each polyploid had at least two distinct homeologs, indicating that all sampled polyploids are likely allopolyploids (rather than autopolyploids). Our divergence-time analyses revealed that these allopolyploid lineages originated recently-within the last two million years-and thus that the genus has undergone a recent radiation, correlated with multiple independent allopolyploidizations across the phylogeny. Also, we found strong parental biases in the formation of allopolyploids, with individual diploid species participating multiple times as either the maternal or paternal donor (but not both). Finally, we discuss the role of polyploidy in the evolutionary history of Botrychium and the interspecific reproductive barriers possibly involved in these parental biases.}, } @article {pmid29241941, year = {2018}, author = {Struck, TH and Feder, JL and Bendiksby, M and Birkeland, S and Cerca, J and Gusarov, VI and Kistenich, S and Larsson, KH and Liow, LH and Nowak, MD and Stedje, B and Bachmann, L and Dimitrov, D}, title = {Finding Evolutionary Processes Hidden in Cryptic Species.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {3}, pages = {153-163}, doi = {10.1016/j.tree.2017.11.007}, pmid = {29241941}, issn = {1872-8383}, mesh = {*Biodiversity ; *Genetic Speciation ; *Genetic Variation ; }, abstract = {Cryptic species could represent a substantial fraction of biodiversity. However, inconsistent definitions and taxonomic treatment of cryptic species prevent informed estimates of their contribution to biodiversity and impede our understanding of their evolutionary and ecological significance. We propose a conceptual framework that recognizes cryptic species based on their low levels of phenotypic (morphological) disparity relative to their degree of genetic differentiation and divergence times as compared with non-cryptic species. We discuss how application of a more rigorous definition of cryptic species in taxonomic practice will lead to more accurate estimates of their prevalence in nature, better understanding of their distribution patterns on the tree of life, and increased abilities to resolve the processes underlying their evolution.}, } @article {pmid29241940, year = {2018}, author = {Mariotte, P and Mehrabi, Z and Bezemer, TM and De Deyn, GB and Kulmatiski, A and Drigo, B and Veen, GFC and van der Heijden, MGA and Kardol, P}, title = {Plant-Soil Feedback: Bridging Natural and Agricultural Sciences.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {2}, pages = {129-142}, doi = {10.1016/j.tree.2017.11.005}, pmid = {29241940}, issn = {1872-8383}, mesh = {*Agriculture ; *Conservation of Natural Resources ; Ecology ; Feedback ; *Plants ; *Soil ; }, abstract = {In agricultural and natural systems researchers have demonstrated large effects of plant-soil feedback (PSF) on plant growth. However, the concepts and approaches used in these two types of systems have developed, for the most part, independently. Here, we present a conceptual framework that integrates knowledge and approaches from these two contrasting systems. We use this integrated framework to demonstrate (i) how knowledge from complex natural systems can be used to increase agricultural resource-use efficiency and productivity and (ii) how research in agricultural systems can be used to test hypotheses and approaches developed in natural systems. Using this framework, we discuss avenues for new research toward an ecologically sustainable and climate-smart future.}, } @article {pmid29241683, year = {2018}, author = {Logan, GJ and Wright, MC and Kubicki, AC and Maricich, SM}, title = {Notch pathway signaling in the skin antagonizes Merkel cell development.}, journal = {Developmental biology}, volume = {434}, number = {2}, pages = {207-214}, doi = {10.1016/j.ydbio.2017.12.007}, pmid = {29241683}, issn = {1095-564X}, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/genetics/metabolism ; Hair Follicle/*metabolism ; Merkel Cells/cytology/*metabolism ; Mice ; Mice, Knockout ; Receptors, Notch/genetics/*metabolism ; Signal Transduction/*physiology ; Transcription Factor HES-1/genetics/metabolism ; Vibrissae/metabolism ; }, abstract = {Merkel cells are mechanosensitive skin cells derived from the epidermal lineage whose development requires expression of the basic helix-loop-helix transcription factor Atoh1. The genes and pathways involved in regulating Merkel cell development during embryogenesis are poorly understood. Notch pathway signaling antagonizes Atoh1 expression in many developing body regions, so we hypothesized that Notch signaling might inhibit Merkel cell development. We found that conditional, constitutive overexpression of the Notch intracellular domain (NICD) in mouse epidermis significantly decreased Merkel cell numbers in whisker follicles and touch domes of hairy skin. Conversely, conditional deletion of the obligate NICD binding partner RBPj in the epidermis significantly increased Merkel cell numbers in whisker follicles, led to the development of ectopic Merkel cells outside of touch domes in hairy skin epidermis, and altered the distribution of Merkel cells in touch domes. Deletion of the downstream Notch effector gene Hes1 also significantly increased Merkel cell numbers in whisker follicles. Together, these data demonstrate that Notch signaling regulates Merkel cell production and patterning.}, } @article {pmid29240975, year = {2018}, author = {Agha, M and Ennen, JR and Nowakowski, AJ and Lovich, JE and Sweat, SC and Todd, BD}, title = {Macroecological patterns of sexual size dimorphism in turtles of the world.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {3}, pages = {336-345}, doi = {10.1111/jeb.13223}, pmid = {29240975}, issn = {1420-9101}, abstract = {Sexual size dimorphism (SSD) is a well-documented phenomenon in both plants and animals; however, the ecological and evolutionary mechanisms that drive and maintain SSD patterns across geographic space at regional and global scales are understudied, especially for reptiles. Our goal was to examine geographic variation of turtle SSD and to explore ecological and environmental correlates using phylogenetic comparative methods. We use published body size data on 135 species from nine turtle families to examine how geographic patterns and the evolution of SSD are influenced by habitat specialization, climate (annual mean temperature and annual precipitation) and climate variability, latitude, or a combination of these predictor variables. We found that geographic variation, magnitude and direction of turtle SSD are best explained by habitat association, annual temperature variance and annual precipitation. Use of semi-aquatic and terrestrial habitats was associated with male-biased SSD, whereas use of aquatic habitat was associated with female-biased SSD. Our results also suggest that greater temperature variability is associated with female-biased SSD. In contrast, wetter climates are associated with male-biased SSD compared with arid climates that are associated with female-biased SSD. We also show support for a global latitudinal trend in SSD, with females being larger than males towards the poles, especially in the families Emydidae and Geoemydidae. Estimates of phylogenetic signal for both SSD and habitat type indicate that closely related species occupy similar habitats and exhibit similar direction and magnitude of SSD. These global patterns of SSD may arise from sex-specific reproductive behaviour, fecundity and sex-specific responses to environmental factors that differ among habitats and vary systematically across latitude. Thus, this study adds to our current understanding that while SSD can vary dramatically across and within turtle species under phylogenetic constraints, it may be driven, maintained and exaggerated by habitat type, climate and geographic location.}, } @article {pmid29240920, year = {2018}, author = {Raymond, B and Federici, BA}, title = {An appeal for a more evidence based approach to biopesticide safety in the EU.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix169}, pmid = {29240920}, issn = {1574-6941}, mesh = {Animals ; Bacillus cereus ; *Bacillus thuringiensis ; Biological Control Agents ; Humans ; Insecta ; *Insecticides ; }, abstract = {EFSA responded to our perspective article on the safe use of the insect pathogen Bacillus thrurigiensis (Bt). In doing so they admitted that there is no direct evidence to suggest that B. thuringiensis can cause diarrhoea. They nevertheless continue to repeat the assertion that Bt cannot be distinguished from Bacillus cereus, even though nearly all Bt strains, and certainly all biopesticide strains, can be distinguished from B. cereus using multi-locus sequencing typing. EFSA also continue to repeat the unsupported and speculative hypothesis that Bt strains could be capable of causing cryptic infections in humans. This hypothesis is very much against the weight of all available safety and epidemiological data. Moreover, genotyping schemes of B. cereus group clinical infections also show that biopesticide strains have never been associated with human infections. Our position that Bt biopesticides and Bt isolates from the clade dominated by invertebrate pathogens are incapable of causing infections in humans is well supported by the international community of scientists familiar with the data on the safety of Bt after more than four decades of extensive use in agriculture and forestry.}, } @article {pmid29239769, year = {2018}, author = {Fondi, M}, title = {Modelling the Kinetic Response to Nutrient Fluctuations.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {4-5}, doi = {10.1016/j.tim.2017.11.009}, pmid = {29239769}, issn = {1878-4380}, mesh = {Biomass ; Escherichia coli/*genetics ; Gene Expression ; *Gene Expression Regulation, Bacterial ; }, abstract = {Understanding and predicting how microbes respond to environmental fluctuations is a central challenge in present-day microbiology. Erickson et al. have proposed a quantitative and (kinetic) parameters-free model of Escherichia coli growth that successfully anticipates changes in gene expression and biomass accumulation in response to nutrients up- and down-shifts.}, } @article {pmid29239717, year = {2018}, author = {Cai, H and Cui, H and Zeng, Y and Wang, Y and Jiang, H}, title = {Niveispirillum lacus sp. nov., isolated from cyanobacterial aggregates in a eutrophic lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {507-512}, doi = {10.1099/ijsem.0.002526}, pmid = {29239717}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; Cyanobacteria/classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; *Eutrophication ; Fatty Acids/chemistry ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodospirillaceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A bacterial strain, 1-14T, was isolated from cyanobacterial aggregates in a eutrophic lake, Taihu Lake, China. Cells were observed to be slightly curved, rod-shaped, aerobic and Gram-stain-negative. Optimal growth occurred at pH 7.0 (range: 5.0-9.0), 28 °C (range: 20-32 °C) and 0 % (w/v) NaCl (range: 0-1.0 %) in R2A broth. No growth is observed at 37 °C. The cells were found to be positive for oxidase and catalase activities. The major respiratory quinone was ubiquinone Q-10. The major fatty acids (>10 %) were identified as C18 : 1ω6c/C18 : 1ω7c, C16 : 0 3-OH and C18 : 1 2-OH. The major polar lipids were found to consist of phosphatidylethanolamine, phosphatidylmonomethylethanolamine, phosphatidylglycerol and phosphatidylcholine. Within the genus Niveispirillum, strain 1-14T was most closely related to Niveispirillum cyanobacteriorum TH16T (98.3 % 16S rRNA gene sequence similarity), followed by Niveispirillum irakense DSM 11586T (97.8 %) and Niveispirillum fermenti CC-LY736T (97.0 %). The genomic G+C content of strain 1-14T was 62.2 mol% based on total genome calculations. Genes coding for light-harvesting complexes LHI and LHII, and a photosynthetic reaction centre were detected in the genome. Average nucleotide identities and digital DNA-DNA hybridizations for complete genomes ranged from 76.4 to 83.5 and from 21.5 to 27.4 % between strain 1-14T and strains within the genus Niveispirillum. The phenotypic, chemotaxonomic and phylogenetic properties, and genome analysis suggested that strain 1-14T represents a novel species within the genus Niveispirillum, for which the name Niveispirillum lacus sp. nov. is proposed. The type strain is 1-14T (=CGMCC 1.12980T=LMG 28363T).}, } @article {pmid29239716, year = {2018}, author = {Sudan, SK and Pal, D and Bisht, B and Kumar, N and Chaudhry, V and Patil, P and Sahni, G and Mayilraj, S and Krishnamurthi, S}, title = {Pseudomonas fluvialis sp. nov., a novel member of the genus Pseudomonas isolated from the river Ganges, India.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {402-408}, doi = {10.1099/ijsem.0.002520}, pmid = {29239716}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; India ; Nucleic Acid Hybridization ; *Phylogeny ; Pigmentation ; Pseudomonas/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; *Water Microbiology ; }, abstract = {A bacterial strain, designated ASS-1T, was isolated and identified from a sediment sample of the river Ganges, Allahabad, India. The strain was Gram-stain-negative, formed straw-yellow pigmented colonies, was strictly aerobic, motile with a single polar flagellum, and positive for oxidase and catalase. The major fatty acids were C16 : 1ω7c/ 16 : 1 C16 : 1ω6c, C18 : 1ω7c and C16 : 0. Sequence analysis based on the 16S rRNA gene revealed that strain ASS-1T showed high similarity to Pseudomonas guguanensis CC-G9AT (98.2 %), Pseudomonas alcaligenes ATCC 14909T (98.2 %), Pseudomonas oleovorans DSM 1045T (98.1 %), Pseudomonas indolxydans IPL-1T (98.1 %) and Pseudomonas toyotomiensis HT-3T (98.0 %). Analysis of its rpoB and rpoD housekeeping genes confirmed its phylogenetic affiliation and showed identities lower than 93 % with respect to the closest relatives. Phylogenetic analysis based on the 16S rRNA, rpoB, rpoD genes and the whole genome assigned it to the genus Pseudomonas. The results of digital DNA-DNA hybridization based on the genome-to-genome distance calculator and average nucleotide identity revealed low genome relatedness to its close phylogenetic neighbours (below the recommended thresholds of 70 and 95 %, respectively, for species delineation). Strain ASS-1T also differed from the related strains by some phenotypic characteristics, i.e. growth at pH 5.0 and 42 °C, starch and casein hydrolysis, and citrate utilization. Therefore, based on data obtained from phenotypic and genotypic analysis, it is evident that strain ASS-1T should be regarded as a novel species within the genus Pseudomonas, for which the name Pseudomonasfluvialis sp. nov. is proposed. The type strain is ASS-1T (=KCTC 52437T=CCM 8778T).}, } @article {pmid29239713, year = {2018}, author = {Puche, R and Ferrés, I and Caraballo, L and Rangel, Y and Picardeau, M and Takiff, H and Iraola, G}, title = {Leptospira venezuelensis sp. nov., a new member of the intermediate group isolated from rodents, cattle and humans.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {513-517}, doi = {10.1099/ijsem.0.002528}, pmid = {29239713}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Cattle/microbiology ; DNA, Bacterial/genetics ; Humans ; Leptospira/*classification/genetics/isolation & purification ; Leptospirosis/microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rats/microbiology ; Sequence Analysis, DNA ; Venezuela ; }, abstract = {Three strains, CLM-U50T, CLM-R50 and IVIC-Bov1, belonging to the genus Leptospira, were isolated in Venezuela from a patient with leptospirosis, a domestic rat (Rattus norvegicus) and a cow (Bos taurus), respectively. The initial characterisation of these strains based on the rrs gene (16S rRNA) suggested their designation as a novel species within the 'intermediates' group of the genus Leptospira. Further phylogenomic characterisation based on single copy core genes was consistent with their separation into a novel species. The average nucleotide identity between these three strains was >99 %, but below 89 % with respect to any previously described leptospiral species, also supporting their designation as a novel species. Given this evidence, these three isolates were considered to represent a novel species, for which the name Leptospiravenezuelensis sp. nov. is proposed, with CLM-U50T (=CIP 111407T=DSM 105752T) as the type strain.}, } @article {pmid29238970, year = {2018}, author = {Martinossi-Allibert, I and Savković, U and Đorđević, M and Arnqvist, G and Stojković, B and Berger, D}, title = {The consequences of sexual selection in well-adapted and maladapted populations of bean beetles†.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {518-530}, doi = {10.1111/evo.13412}, pmid = {29238970}, issn = {1558-5646}, abstract = {Whether sexual selection generally promotes or impedes population persistence remains an open question. Intralocus sexual conflict (IaSC) can render sexual selection in males detrimental to the population by increasing the frequency of alleles with positive effects on male reproductive success but negative effects on female fecundity. Recent modeling based on fitness landscape theory, however, indicates that the relative impact of IaSC may be reduced in maladapted populations and that sexual selection therefore might promote adaptation when it is most needed. Here, we test this prediction using bean beetles that had undergone 80 generations of experimental evolution on two alternative host plants. We isolated and assessed the effect of maladaptation on sex-specific strengths of selection and IaSC by cross-rearing the two experimental evolution regimes on the alternative hosts and estimating within-population genetic (co)variance for fitness in males and females. Two key predictions were upheld: males generally experienced stronger selection compared to females and maladaptation increased selection in females. However, maladaptation consistently decreased male-bias in the strength of selection and IaSC was not reduced in maladapted populations. These findings imply that sexual selection can be disrupted in stressful environmental conditions, thus reducing one of the potential benefits of sexual reproduction in maladapted populations.}, } @article {pmid29238958, year = {2018}, author = {Turko, P and Tellenbach, C and Keller, E and Tardent, N and Keller, B and Spaak, P and Wolinska, J}, title = {Parasites driving host diversity: Incidence of disease correlated with Daphnia clonal turnover.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {3}, pages = {619-629}, doi = {10.1111/evo.13413}, pmid = {29238958}, issn = {1558-5646}, abstract = {According to the Red Queen hypothesis, clonal diversity in asexual populations could be maintained by negative frequency-dependant selection by coevolving parasites. If common clones are selected against and rare clones gain a concomitant advantage, we expect that clonal turnover should be faster during parasite epidemics than between them. We tested this hypothesis exploring field data of the Daphnia-Caullerya host-parasite system. The clonal make-up and turnover of the Daphnia host population was tracked with high temporal resolution from 1998 until 2013, using first allozyme and later microsatellite markers. Significant differences in the clonal composition between random and infected subsamples of Daphnia populations were detected on six of seven tested occasions, confirming genetic specificity of the host-parasite interaction in this system. We used time series analysis to compare the rates of host clonal turnover to the incidence of parasitism, and found that Caullerya prevalence was significantly associated with microsatellite-based clonal turnover. As alternate hypotheses, we further tested whether turnover was related to a variety of biotic, abiotic, and host demographic parameters. Other significant correlates of turnover were cyanobacterial biomass and (weakly) temperature. Overall, parasitism seems to be a strong driver of host clonal turnover, in support of the Red Queen hypothesis.}, } @article {pmid29236690, year = {2018}, author = {Waldron, A and Miller, DC and Redding, D and Mooers, A and Kuhn, TS and Nibbelink, N and Roberts, JT and Tobias, JA and Gittleman, JL}, title = {Corrigendum: Reductions in global biodiversity loss predicted from conservation spending.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {530}, pmid = {29236690}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24295.}, } @article {pmid29236689, year = {2018}, author = {Harper, KL and Sosa, MS and Entenberg, D and Hosseini, H and Cheung, JF and Nobre, R and Avivar-Valderas, A and Nagi, C and Girnius, N and Davis, RJ and Farias, EF and Condeelis, J and Klein, CA and Aguirre-Ghiso, JA}, title = {Corrigendum: Mechanism of early dissemination and metastasis in Her2+ mammary cancer.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {366}, doi = {10.1038/nature24666}, pmid = {29236689}, issn = {1476-4687}, support = {R01 CA109182/CA/NCI NIH HHS/United States ; }, abstract = {This corrects the article DOI: 10.1038/nature20609.}, } @article {pmid29236687, year = {2018}, author = {Pangala, SR and Enrich-Prast, A and Basso, LS and Peixoto, RB and Bastviken, D and Hornibrook, ERC and Gatti, LV and Marotta, H and Calazans, LSB and Sakuragui, CM and Bastos, WR and Malm, O and Gloor, E and Miller, JB and Gauci, V}, title = {Erratum: Large emissions from floodplain trees close the Amazon methane budget.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {366}, doi = {10.1038/nature25191}, pmid = {29236687}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24639.}, } @article {pmid29236686, year = {2018}, author = {Martín-Durán, JM and Pang, K and Børve, A and Lê, HS and Furu, A and Cannon, JT and Jondelius, U and Hejnol, A}, title = {Convergent evolution of bilaterian nerve cords.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {45-50}, pmid = {29236686}, issn = {1476-4687}, support = {648861//European Research Council/International ; }, mesh = {Animals ; Annelida/anatomy & histology/embryology ; *Biological Evolution ; Body Patterning ; Central Nervous System/*anatomy & histology/*embryology ; Invertebrates/anatomy & histology/embryology ; Nerve Net/*anatomy & histology/*embryology ; Neural Plate/anatomy & histology/embryology ; Phylogeny ; Rotifera/anatomy & histology/embryology ; }, abstract = {It has been hypothesized that a condensed nervous system with a medial ventral nerve cord is an ancestral character of Bilateria. The presence of similar dorsoventral molecular patterns along the nerve cords of vertebrates, flies, and an annelid has been interpreted as support for this scenario. Whether these similarities are generally found across the diversity of bilaterian neuroanatomies is unclear, and thus the evolutionary history of the nervous system is still contentious. Here we study representatives of Xenacoelomorpha, Rotifera, Nemertea, Brachiopoda, and Annelida to assess the conservation of the dorsoventral nerve cord patterning. None of the studied species show a conserved dorsoventral molecular regionalization of their nerve cords, not even the annelid Owenia fusiformis, whose trunk neuroanatomy parallels that of vertebrates and flies. Our findings restrict the use of molecular patterns to explain nervous system evolution, and suggest that the similarities in dorsoventral patterning and trunk neuroanatomies evolved independently in Bilateria.}, } @article {pmid29235981, year = {2018}, author = {Nahar, S and Cha, CJ}, title = {Paenibacillus limicola sp. nov., isolated from tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {423-426}, doi = {10.1099/ijsem.0.002522}, pmid = {29235981}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Paenibacillus/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An aerobic, Gram-staining-variable, rod-shaped, endospore-forming and motile bacterial strain, designated CJ6T, was isolated from a tidal flat on Ganghwa Island, South Korea. The isolate was characterized based on a polyphasic taxonomy approach. Strain CJ6T grew optimally on R2A agar media at 30 °C and pH 7. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that strain CJ6T belonged to the genus Paenibacillus, displaying the highest sequence similarity to Paenibacillus vulneris CCUG 53270T (97.0 %) and clearly defined strain CJ6T as a novel species within the genus. The G+C content of the genomic DNA was 49.9 mol%. The major polar lipid contents of strain CJ6T were phosphatidylmonomethylethanolamine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and unidentified glycolipids. MK-7 was detected as the major respiratory quinone. The dominant fatty acid was anteiso-C15 : 0. Analyses of phylogenetic, phenotypic, biochemical and chemotaxonomic characteristics indicated that strain CJ6T was distinguishable from its closely related type strains. Therefore, strain CJ6T represents a novel species in the genus Paenibacillus, for which name Paenibacilluslimicola sp. nov. is proposed; the type strain is CJ6T (=KACC 19303T=JCM 32079T).}, } @article {pmid29235979, year = {2018}, author = {Ueki, A and Goto, K and Kaku, N and Ueki, K}, title = {Aminipila butyrica gen. nov., sp. nov., a strictly anaerobic, arginine-decomposing bacterium isolated from a methanogenic reactor of cattle waste.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {443-448}, doi = {10.1099/ijsem.0.002534}, pmid = {29235979}, issn = {1466-5034}, mesh = {Animals ; Arginine/*metabolism ; Bacteria, Anaerobic/classification ; Bacterial Typing Techniques ; Base Composition ; Bioreactors/*microbiology ; Cattle ; Clostridiales/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Japan ; Manure/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A strictly anaerobic bacterial strain (FH042T) was isolated from a methanogenic reactor treating waste from cattle farms. Cells were stained Gram-positive, straight to gently curved rods with polar flagella. The strain was asaccharolytic. The strain fermented amino acids (l-arginine, l-lysine and l-serine) as growth substrates and produced acetate and butyrate. The optimum temperature for growth was 30 °C and the optimum pH was 6.1-6.8. Oxidase, catalase and nitrate-reducing activities were negative. Hydrogen sulfide was produced. The genomic DNA G+C content of strain FH042T was 44.7±0.2 mol%. The major cellular fatty acids were C18 : 1ω9c DMA, C17 : 2/C17 : 1ω9c (as summed feature), C16 : 0 DMA and C14 : 0. The cell-wall peptidoglycan contained meso-diaminopimelic acid as a diagnostic amino acid. The most closely related described species on the basis of 16S rRNA gene sequences was Anaerovorax odorimutans in the family XIII Incertae Sedis in the order Clostridiales of the class Clostridia with sequence similarity of 95.1 %. Based on the distinct differences in phylogenetic and phenotypic characteristics between strain FH042T and related species, Aminipila butyrica gen. nov., sp. nov. is proposed to accommodate the strain. Type strain is FH042T (=JCM 31555T=DSM 103574T).}, } @article {pmid29235976, year = {2018}, author = {Sheu, SY and Xie, PB and Sheu, DS and Tang, SL and Chen, WM}, title = {Litoribrevibacter euphylliae sp. nov., isolated from the torch coral Euphyllia glabrescens.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {432-437}, doi = {10.1099/ijsem.0.002529}, pmid = {29235976}, issn = {1466-5034}, mesh = {Animals ; Anthozoa/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Oceanospirillaceae/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Strain Eup a-2T, isolated from the torch coral Euphyllia glabrescens, was characterized using a polyphasic taxonomy approach. Cells of strain Eup a-2T were Gram-negative, aerobic and motile by three polar flagella and formed translucent colonies. Optimal growth occurred at 25 °C, pH 6-8 and in the presence of 2-4 % NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Eup a-2T belonged to the genus Litoribrevibacter and showed the highest levels of sequence similarity with respect to Litoribrevibacter albus Y32T (97.8 %). Strain Eup a-2T contained summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0 as the predominant fatty acids. The predominant isoprenoid quinone was Q-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and diphophatidylglycerol. Genomic DNA G+C content of strain Eup a-2T was 49.1 mol%. The DNA-DNA hybridization value for strain Eup a-2T with L. albus Y32T was less than 30 %. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain Eup a-2T should be classified as a novel species of the genus Litoribrevibacter, for which the name Litoribrevibactereuphylliae sp. nov. is presented. The type strain is Eup a-2T (=BCRC 81004T=LMG 29725T=KCTC 52438T).}, } @article {pmid29235725, year = {2018}, author = {Showalter, GM and Deming, JW}, title = {Low-temperature chemotaxis, halotaxis and chemohalotaxis by the psychrophilic marine bacterium Colwellia psychrerythraea 34H.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {92-101}, doi = {10.1111/1758-2229.12610}, pmid = {29235725}, issn = {1758-2229}, abstract = {A variety of ecologically important processes are driven by bacterial motility and taxis, yet these basic bacterial behaviours remain understudied in cold habitats. Here, we present a series of experiments designed to test the chemotactic ability of the model marine psychrophilic bacterium Colwellia psychrerythraea 34H, when grown at optimal temperature and salinity (8°C, 35 ppt) or its original isolation conditions (-1°C, 35 ppt), towards serine and mannose at temperatures from -8°C to 27°C (above its upper growth temperature of 18°C), and at salinities of 15, 35 and 55 ppt (at 8°C and -1°C). Results indicate that C. psychrerythraea 34H is capable of chemotaxis at all temperatures tested, with strongest chemotaxis at the temperature at which it was first grown, whether 8°C or -1°C. This model marine psychrophile also showed significant halotaxis towards 15 and 55 ppt solutions, as well as strong substrate-specific chemohalotaxis. We suggest that such patterns of taxis may enable bacteria to colonize sea ice, position themselves optimally within its extremely cold, hypersaline and temporally fluctuating microenvironments, and respond to various chemical signals therein.}, } @article {pmid29235714, year = {2018}, author = {Topçuoğlu, BD and Meydan, C and Orellana, R and Holden, JF}, title = {Formate hydrogenlyase and formate secretion ameliorate H2 inhibition in the hyperthermophilic archaeon Thermococcus paralvinellae.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {949-957}, doi = {10.1111/1462-2920.14022}, pmid = {29235714}, issn = {1462-2920}, abstract = {Some hyperthermophilic heterotrophs in the genus Thermococcus produce H2 in the absence of S° and have up to seven hydrogenases, but their combined physiological roles are unclear. Here, we show which hydrogenases in Thermococcus paralvinellae are affected by added H2 during growth without S°. Growth rates and steady-state cell concentrations decreased while formate production rates increased when T. paralvinallae was grown in a chemostat with 65 µM of added H2(aq) . Differential gene expression analysis using RNA-Seq showed consistent expression of six hydrogenase operons with and without added H2 . In contrast, expression of the formate hydrogenlyase 1 (fhl1) operon increased with added H2 . Flux balance analysis showed H2 oxidation and formate production using FHL became an alternate route for electron disposal during H2 inhibition with a concomitant increase in growth rate relative to cells without FHL. T. paralvinellae also grew on formate with an increase in H2 production rate relative to growth on maltose or tryptone. Growth on formate increased fhl1 expression but decreased expression of all other hydrogenases. Therefore, Thermococcus that possess fhl1 have a competitive advantage over other Thermococcus species in hot subsurface environments where organic substrates are present, S° is absent and slow H2 efflux causes growth inhibition.}, } @article {pmid29235710, year = {2018}, author = {Xie, W and Luo, H and Murugapiran, SK and Dodsworth, JA and Chen, S and Sun, Y and Hedlund, BP and Wang, P and Fang, H and Deng, M and Zhang, CL}, title = {Localized high abundance of Marine Group II archaea in the subtropical Pearl River Estuary: implications for their niche adaptation.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {734-754}, doi = {10.1111/1462-2920.14004}, pmid = {29235710}, issn = {1462-2920}, abstract = {Marine Group II archaea are widely distributed in global oceans and dominate the total archaeal community within the upper euphotic zone of temperate waters. However, factors controlling the distribution of MGII are poorly delineated and the physiology and ecological functions of these still-uncultured organisms remain elusive. In this study, we investigated the planktonic MGII associated with particles and in free-living forms in the Pearl River Estuary (PRE) over a 10-month period. We detected high abundance of particle-associated MGII in PRE (up to ∼108 16S rRNA gene copies/l), which was around 10-fold higher than the free-living MGII in the same region, and an order of magnitude higher than previously reported in other marine environments. 10‰ salinity appeared to be a threshold value for these MGII because MGII abundance decreased sharply below it. Above 10‰ salinity, the abundance of MGII on the particles was positively correlated with phototrophs and MGII in the surface water was negatively correlated with irradiance. However, the abundances of those free-living MGII showed positive correlations with salinity and temperature, suggesting the different physiological characteristics between particle-attached and free-living MGIIs. A nearly completely assembled metagenome, MGIIa_P, was recovered using metagenome binning methods. Compared with the other two MGII genomes from surface ocean, MGIIa_P contained higher proportions of glycoside hydrolases, indicating the ability of MGIIa_P to hydrolyse glycosidic bonds in complex sugars in PRE. MGIIa_P is the first assembled MGII metagenome containing a catalase gene, which might be involved in scavenging reactive oxygen species generated by the abundant phototrophs in the eutrophic PRE. Our study presented the widespread and high abundance of MGII in the water columns of PRE, and characterized the determinant abiotic factors affecting their distribution. Their association with heterotrophs, preference for particles and resourceful metabolic traits indicate MGII might play a significant role in metabolising organic matters in the PRE and other temperate estuarine systems.}, } @article {pmid29235709, year = {2018}, author = {Katariya, L and Ramesh, PB and Borges, RM}, title = {Dynamic environments of fungus-farming termite mounds exert growth-modulating effects on fungal crop parasites.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {971-979}, doi = {10.1111/1462-2920.14026}, pmid = {29235709}, issn = {1462-2920}, abstract = {This study investigated for the first time the impact of the internal mound environment of fungus-growing termites on the growth of fungal crop parasites. Mounds of the termite Odontotermes obesus acted as (i) temperature and relative humidity (RH) 'stabilisers' showing dampened daily variation and (ii) 'extreme environments' exhibiting elevated RH and CO2 levels, compared to the outside. Yet, internal temperatures exhibited seasonal dynamics as did daily and seasonal CO2 levels. During in situ experiments under termite-excluded conditions within the mound, the growth of the crop parasite Pseudoxylaria was greater inside than outside the mound, i.e., Pseudoxylaria is 'termitariophilic'. Also, ex situ experiments on parasite isolates differing in growth rates and examined under controlled conditions in the absence of termites revealed a variable effect with fungal growth decreasing only under high CO2 and low temperature conditions, reflecting the in situ parasite growth fluctuations. In essence, the parasite appears to be adapted to survive in the termite mound. Thus the mound microclimate does not inhibit the parasite but the dynamic environmental conditions of the mound affect its growth to varying extents. These results shed light on the impact of animal-engineered structures on parasite ecology, independent of any direct role of animal engineers.}, } @article {pmid29235707, year = {2018}, author = {Brewer, TE and Fierer, N}, title = {Tales from the tomb: the microbial ecology of exposed rock surfaces.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {958-970}, doi = {10.1111/1462-2920.14024}, pmid = {29235707}, issn = {1462-2920}, abstract = {Although a broad diversity of eukaryotic and bacterial taxa reside on rock surfaces where they can influence the weathering of rocks and minerals, these communities and their contributions to mineral weathering remain poorly resolved. To build a more comprehensive understanding of the diversity, ecology and potential functional attributes of microbial communities living on rock, we sampled 149 tombstones across three continents and analysed their bacterial and eukaryotic communities via marker gene and shotgun metagenomic sequencing. We found that geographic location and climate were important factors structuring the composition of these communities. Moreover, the tombstone-associated microbial communities varied as a function of rock type, with granite and limestone tombstones from the same cemeteries harbouring taxonomically distinct microbial communities. The granite and limestone-associated communities also had distinct functional attributes, with granite-associated bacteria having more genes linked to acid tolerance and chemotaxis, while bacteria on limestone were more likely to be lichen associated and have genes involved in photosynthesis and radiation resistance. Together these results indicate that rock-dwelling microbes exhibit adaptations to survive the stresses of the rock surface, differ based on location, climate and rock type, and seem pre-disposed to different ecological strategies (symbiotic versus free-living lifestyles) depending on the rock type.}, } @article {pmid29235706, year = {2018}, author = {Pu, M and Duriez, P and Arazi, M and Rowe-Magnus, DA}, title = {A conserved tad pilus promotes Vibrio vulnificus oyster colonization.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {828-841}, doi = {10.1111/1462-2920.14025}, pmid = {29235706}, issn = {1462-2920}, abstract = {Vibrio vulnificus has the highest death rate (>35%) and per-case economic burden ($3.3 million) of any foodborne pathogen in the United States. Infections occur via open wounds or following ingestion of contaminated seafood, most infamously oysters. We isolated a 1000th generation descendant, designated NT that exhibited increased biofilm and aggregate formation relative to its parent. We identified two significant causal changes underlying these phenotypes. First, the entire 24-kb capsular polysaccharide biosynthesis locus, which is essential for virulence but inhibits biofilm formation, had been purged from the genome. However, NT formed more extensive biofilms and aggregates than a defined cps mutant, suggesting that additional factor(s) contributed to its phenotypes. Second, the expression of a tight adherence (tad) pilus locus was elevated in NT. Deletion of the associated pilin (flp) decreased NT biofilm and aggregate formation. Furthermore, NTΔflp strains were deficient relative to NT in an oyster colonization model, demonstrating a positive correlation between the biofilm and aggregation phenotypes associated with Tad pilus production and efficient bacterial retention by feeding oysters. Despite being widely distributed in the Vibrionaceae, this is the first demonstration of a bona fide physiological role for a Tad pilus in this bacterial family.}, } @article {pmid29235117, year = {2018}, author = {Joly, S and Lambert, F and Alexandre, H and Clavel, J and Léveillé-Bourret, É and Clark, JL}, title = {Greater pollination generalization is not associated with reduced constraints on corolla shape in Antillean plants.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {244-260}, doi = {10.1111/evo.13410}, pmid = {29235117}, issn = {1558-5646}, abstract = {Flowers show important structural variation as reproductive organs but the evolutionary forces underlying this diversity are still poorly understood. In animal-pollinated species, flower shape is strongly fashioned by selection imposed by pollinators, which is expected to vary according to guilds of effective pollinators. Using the Antillean subtribe Gesneriinae (Gesneriaceae), we tested the hypothesis that pollination specialists pollinated by one functional type of pollinator have maintained more similar corolla shapes through time due to more constant and stronger selection constraints compared to species with more generalist pollination strategies. Using geometric morphometrics and evolutionary models, we showed that the corolla of hummingbird specialists, bat specialists, and species with a mixed-pollination strategy (pollinated by hummingbirds and bats; thus a more generalist strategy) have distinct shapes and that these shapes have evolved under evolutionary constraints. However, we did not find support for greater disparity in corolla shape of more generalist species. This could be because the corolla shape of more generalist species in subtribe Gesneriinae, which has evolved multiple times, is finely adapted to be effectively pollinated by both bats and hummingbirds. These results suggest that ecological generalization is not necessarily associated with relaxed selection constraints.}, } @article {pmid29235104, year = {2018}, author = {Rego-Costa, A and Débarre, F and Chevin, LM}, title = {Chaos and the (un)predictability of evolution in a changing environment.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {375-385}, pmid = {29235104}, issn = {1558-5646}, support = {678140//European Research Council/International ; }, abstract = {Among the factors that may reduce the predictability of evolution, chaos, characterized by a strong dependence on initial conditions, has received much less attention than randomness due to genetic drift or environmental stochasticity. It was recently shown that chaos in phenotypic evolution arises commonly under frequency-dependent selection caused by competitive interactions mediated by many traits. This result has been used to argue that chaos should often make evolutionary dynamics unpredictable. However, populations also evolve largely in response to external changing environments, and such environmental forcing is likely to influence the outcome of evolution in systems prone to chaos. We investigate how a changing environment causing oscillations of an optimal phenotype interacts with the internal dynamics of an eco-evolutionary system that would be chaotic in a constant environment. We show that strong environmental forcing can improve the predictability of evolution by reducing the probability of chaos arising, and by dampening the magnitude of chaotic oscillations. In contrast, weak forcing can increase the probability of chaos, but it also causes evolutionary trajectories to track the environment more closely. Overall, our results indicate that, although chaos may occur in evolution, it does not necessarily undermine its predictability.}, } @article {pmid29234881, year = {2018}, author = {Han, R and Yuan, Y and Cao, Q and Li, Q and Chen, L and Zhu, D and Liu, D}, title = {PCR-DGGE Analysis on Microbial Community Structure of Rural Household Biogas Digesters in Qinghai Plateau.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {541-549}, pmid = {29234881}, issn = {1432-0991}, support = {31560039//National Natural Science Foundation of China/ ; 2015-ZJ-730//Applied Basic Research Program of Qinghai Province/ ; 2015-ZJ-929Q//Natural Science Foundation of Qinghai Province/ ; 2016-NK-A8//Qinghai Special Project for Key Science and Technology/ ; }, mesh = {Archaea/classification/genetics/*isolation & purification/metabolism ; Bacteria/classification/genetics/*isolation & purification/metabolism ; Biodiversity ; Biofuels/*analysis ; China ; Denaturing Gradient Gel Electrophoresis ; Fermentation ; Gases/*metabolism ; Polymerase Chain Reaction ; Sewage/*microbiology ; }, abstract = {To investigate contribution of environmental factor(s) to microbial community structure(s) involved in rural household biogas fermentation at Qinghai Plateau, we collected slurry samples from 15 digesters, with low-temperature working conditions (11.1-15.7 °C) and evenly distributed at three counties (Datong, Huangyuan, and Ledu) with cold plateau climate, to perform polymerase chain reaction-denaturing gradient gel electrophoresis (PCR-DGGE) and further sequencing. The bacterial communities in the total 15 digesters were classified into 38 genera with Mangroviflexus (12.1%) as the first dominant, and the archaeal communities into ten genera with Methanogenium (38.5%) as the most dominant. For each county, the digesters with higher biogas production, designated as HP digesters, exclusively had 1.6-3.1 °C higher fermentation temperature and the unique bacterial structure composition related, i.e., unclassified Clostridiales for all the HP digesters and unclassified Marinilabiliaceae and Proteiniclasticum for Ledu HP digesters. Regarding archaeal structure composition, Methanogenium exhibited significantly higher abundances at all the HP digesters and Thermogymnomonas was the unique species only identified at Ledu HP digesters with higher-temperature conditions. Redundancy analysis also confirmed the most important contribution of temperature to the microbial community structures investigated. This report emphasized the correlation between temperature and specific microbial community structure(s) that would benefit biogas production of rural household digesters at Qinghai Plateau.}, } @article {pmid29234139, year = {2018}, author = {Parks, DH and Rinke, C and Chuvochina, M and Chaumeil, PA and Woodcroft, BJ and Evans, PN and Hugenholtz, P and Tyson, GW}, title = {Author Correction: Recovery of nearly 8,000 metagenome-assembled genomes substantially expands the tree of life.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {253}, doi = {10.1038/s41564-017-0083-5}, pmid = {29234139}, issn = {2058-5276}, abstract = {In the original version of this Article, the authors stated that the archaeal phylum Parvarchaeota was previously represented by only two single-cell genomes (ARMAN-4_'5-way FS' and ARMAN-5_'5-way FS'). However, these are in fact unpublished, low-quality metagenome-assembled genomes (MAGs) obtained from Richmond Mine, California. In addition, the authors overlooked two higher-quality published Parvarchaeota MAGs from the same habitat, ARMAN-4 (ADCE00000000) and ARMAN-5 (ADHF00000000) (B. J. Baker et al., Proc. Natl Acad. Sci. USA 107, 8806-8811; 2010). The ARMAN-4 and ARMAN-5 MAGs are estimated to be 68.0% and 76.7% complete with 3.3% and 5.6% contamination, respectively, based on the archaeal-specific marker sets of CheckM. The 11 Parvarchaeota genomes identified in our study were obtained from different Richmond Mine metagenomes, but are highly similar to the ARMAN-4 (ANI of ~99.7%) and ARMAN-5 (ANI of ~99.6%) MAGs. The highest-quality uncultivated bacteria and archaea (UBA) MAGs with similarity to ARMAN-4 and ARMAN-5 are 82.5% and 83.3% complete with 0.9% and 1.9% contamination, respectively. The Parvarchaeota represents only 0.23% of the archaeal genome tree and addition of the ARMAN-4 and ARMAN-5 MAGs do not change the conclusions of this Article, but do impact the phylogenetic gain for this phylum. This has now been corrected in all versions of the Article. An updated version of Fig. 5 has also been used to replace the previous version, with the row for Parvarchaeota removed, and Supplementary Table 15 and Supplementary Table 17 have both been replaced to reflect the availability of the two additional Parvarchaeota genomes. In addition, the Methods incorrectly stated that all metagenomes identified as being from studies where MAGs had previously been recovered were excluded from consideration. Metagenomes from studies where MAGs had previously been recovered were retained if the UBA MAGs provided appreciable improvements in genome quality or phylogenetic diversity. All versions of the Article have been updated to indicate the retention of such metagenomes.}, } @article {pmid29233941, year = {2018}, author = {Liu, JL}, title = {Implantation in eutherians: Which came first, the inflammatory reaction or attachment?.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E1-E2}, pmid = {29233941}, issn = {1091-6490}, mesh = {Animals ; *Embryo Implantation ; *Eutheria ; Marsupialia ; }, } @article {pmid29233940, year = {2018}, author = {Griffith, OW and Chavan, AR and Protopapas, S and Maziarz, J and Romero, R and Wagner, GP}, title = {Reply to Liu: Inflammation before implantation both in evolution and development.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E3-E4}, pmid = {29233940}, issn = {1091-6490}, mesh = {*Embryo Implantation ; Humans ; *Inflammation ; }, } @article {pmid29233707, year = {2018}, author = {Sproles, AE and Kirk, NL and Kitchen, SA and Oakley, CA and Grossman, AR and Weis, VM and Davy, SK}, title = {Phylogenetic characterization of transporter proteins in the cnidarian-dinoflagellate symbiosis.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {307-320}, doi = {10.1016/j.ympev.2017.12.007}, pmid = {29233707}, issn = {1095-9513}, mesh = {Animals ; Anion Transport Proteins/chemistry/classification/genetics ; Aquaporins/chemistry/classification/genetics ; Cnidaria/*classification/metabolism ; Computational Biology ; Dinoflagellida/*classification/metabolism ; *Phylogeny ; Protein Structure, Tertiary ; Sodium-Glucose Transport Proteins/chemistry/classification/genetics ; Symbiosis/physiology ; }, abstract = {Metabolic exchange between cnidarians and their symbiotic dinoflagellates is central to maintaining their mutualistic relationship. Sugars are translocated to the host, while ammonium and nitrate are utilized by the dinoflagellates (Symbiodinium spp.). We investigated membrane protein sequences of each partner to identify potential transporter proteins that move sugars into cnidarian cells and nitrogen products into Symbiodinium cells. We examined the facilitated glucose transporters (GLUT), sodium/glucose cotransporters (SGLT), and aquaporin (AQP) channels in the cnidarian host as mechanisms for sugar uptake, and the ammonium and high-affinity nitrate transporters (AMT and NRT2, respectively) in the algal symbiont as mechanisms for nitrogen uptake. Homologous protein sequences were used for phylogenetic analysis and tertiary structure deductions. In cnidarians, we identified putative glucose transporters of the GLUT family and glycerol transporting AQP proteins, as well as sodium monocarboxylate transporters and sodium myo-inositol cotransporters homologous to SGLT proteins. We hypothesize that cnidarians use GLUT proteins as the primary mechanism for glucose uptake, while glycerol moves into cells by passive diffusion. We also identified putative AMT proteins in several Symbiodinium clades and putative NRT2 proteins only in a single clade. We further observed an upregulation of expressed putative AMT proteins in Symbiodinium, which may have emerged as an adaptation to conditions experienced inside the host cell. This study is the first to identify transporter sequences from a diversity of cnidarian species and Symbiodinium clades, which will be useful for future experimental analyses of the host-symbiont proteome and the nutritional exchange of Symbiodinium cells in hospite.}, } @article {pmid29233706, year = {2018}, author = {Carneiro, L and Bravo, GA and Aristizábal, N and Cuervo, AM and Aleixo, A}, title = {Molecular systematics and biogeography of lowland antpittas (Aves, Grallariidae): The role of vicariance and dispersal in the diversification of a widespread Neotropical lineage.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {375-389}, doi = {10.1016/j.ympev.2017.11.019}, pmid = {29233706}, issn = {1095-9513}, mesh = {Animals ; Biodiversity ; DNA, Mitochondrial/chemistry/classification/genetics ; Genetic Variation ; Introns ; Passeriformes/*classification/genetics ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; South America ; Transforming Growth Factor beta2/classification/genetics/metabolism ; }, abstract = {We infer phylogenetic relationships, divergence times, and the diversification history of the avian Neotropical antpitta genera Hylopezus and Myrmothera (Grallariidae), based on sequence data (3,139 base pairs) from two mitochondrial (ND2 and ND3) and three nuclear nuclear introns (TGFB2, MUSK and FGB-I5) from 142 individuals of the 12 currently recognized species in Hylopezus and Myrmothera and 5 outgroup species. Phylogenetic analyses recovered 19 lineages clustered into two major clades, both distributed in Central and South America. Hylopezus nattereri, previously considered a subspecies of H. ochroleucus, was consistently recovered as the most divergent lineage within the Grallaricula/Hylopezus/Myrmothera clade. Ancestral range estimation suggested that modern lowland antpittas probably originated in the Amazonian Sedimentary basin during the middle Miocene, and that most lineages within the Hylopezus/Myrmothera clade appeared in the Plio-Pleistocene. However, the rate of diversification in the Hylopezus/Myrmothera clade appeared to have remained constant through time, with no major shifts over the 20 million years. Although the timing when most modern lineages of the Hylopezus/Myrmothera clade coincides with a period of intense landscape changes in the Neotropics (Plio-Pleistocene), the absence of any significant shifts in diversification rates over the last 20 million years challenges the view that there is a strict causal relationship between intensification of landscape changes and cladogenesis. The relative old age of the Hylopezus/Myrmothera clade coupled with an important role ascribed to dispersal for its diversification, favor an alternative scenario whereby long-term persistence and dispersal across an ever-changing landscape might explain constant rates of cladogenesis through time.}, } @article {pmid29233705, year = {2018}, author = {Weinell, JL and Bauer, AM}, title = {Systematics and phylogeography of the widely distributed African skink Trachylepis varia species complex.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {103-117}, doi = {10.1016/j.ympev.2017.11.014}, pmid = {29233705}, issn = {1095-9513}, mesh = {Africa ; Animals ; Base Sequence ; Bayes Theorem ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; Discriminant Analysis ; Entropy ; Genetic Loci ; Lizards/*classification/genetics ; Models, Biological ; Phenotype ; Phylogeny ; *Phylogeography ; Principal Component Analysis ; Sequence Analysis, DNA ; Species Specificity ; Time Factors ; }, abstract = {A systematic study of the Trachylepis varia complex was conducted using mitochondrial and nuclear DNA markers for individuals sampled across the species range. The taxonomic history of T. varia has been complicated and its broad geographic distribution and considerable phenotypic variation has made taxonomic revision difficult, leading earlier taxonomists to suggest that T. varia is a species complex. We used maximum likelihood and Bayesian inference to estimate gene trees and a multilocus time-tree, respectively, and we used these trees to identify the major clades (putative species) within T. varia. Additionally, we used morphological and color pattern data to distinguish and revise the taxonomy of the southern African clades. The major clades recovered in the multilocus time-tree were recovered in each of gene trees, although the relationships among these major clades differed across gene trees. Genetic data support the existence of at least eight species within the T.varia complex, each of which originated during the mid to late Miocene or early Pliocene. We focus our systematic discussion on the southern African members of the T. varia complex, revive Trachylepis damarana (Peters, 1870) and T. laevigata (Peters, 1869), and designate lectotypes for T.damarana and T. varia.}, } @article {pmid29233606, year = {2018}, author = {Geoghegan, JA and Irvine, AD and Foster, TJ}, title = {Staphylococcus aureus and Atopic Dermatitis: A Complex and Evolving Relationship.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {484-497}, doi = {10.1016/j.tim.2017.11.008}, pmid = {29233606}, issn = {1878-4380}, abstract = {Staphylococcus aureus is frequently isolated from the skin of atopic dermatitis (AD) patients during flares. The normal microbiota is disrupted and the diversity of the microorganisms on the skin is reduced. Many species that produce inhibitors of S. aureus growth decline. Strains from S. aureus clonal complex 1 are enriched among AD sufferers whereas the CC30 strains most frequently isolated from nasal carriers in the normal population are much rarer in AD. S. aureus expresses several molecules that contribute to the intensity of symptoms, including δ-toxin which stimulates mast cells, α-toxin which damages keratinocytes, phenol-soluble modulins which stimulate cytokine release by keratinocytes, protein A which triggers inflammatory responses from keratinocytes, superantigens which trigger B cell expansion and cytokine release, and proinflammatory lipoproteins. Proteases contribute to disruption of the epidermal barrier. S. aureus isolated from AD patients adheres to the deformed corneocytes from AD patients in a clumping factor B-dependent fashion. Novel targeted therapies for AD have recently been introduced to clinical practice with many more in development, including monoclonal antibodies that specifically target cytokines and their receptors, and a bacteriophage lysin that eliminates S. aureus from AD skin.}, } @article {pmid29232670, year = {2018}, author = {Janušonis, S}, title = {Some Galeomorph Sharks Express a Mammalian Microglia-Specific Protein in Radial Ependymoglia of the Telencephalon.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {1}, pages = {17-30}, pmid = {29232670}, issn = {1421-9743}, support = {S10 OD010610/OD/NIH HHS/United States ; }, abstract = {Ionized calcium-binding adapter molecule 1 (Iba1), also known as allograft inflammatory factor 1 (AIF-1), is a highly conserved cytoplasmic scaffold protein. Studies strongly suggest that Iba1 is associated with immune-like reactions in all Metazoa. In the mammalian brain, it is abundantly expressed in microglial cells and is used as a reliable marker for this cell type. The present study used multiple-label microscopy and Western blotting to examine Iba1 expression in the telencephalon of 2 galeomorph shark species, the swellshark (Cephaloscyllium ventriosum) and the horn shark (Heterodontus francisci), a member of an ancient extant order. In the swellshark, high Iba1 expression was found in radial ependymoglial cells, many of which also expressed glial fibrillary acidic protein. Iba1 expression was absent from most cells in the horn shark (with the possible exception of perivascular cells). The difference in Iba1 expression between the species was supported by protein analysis. These results suggest that radial ependymoglia of the elasmobranchs may be functionally related to mammalian microglia and that Iba1 expression has undergone evolutionary changes in this cartilaginous group.}, } @article {pmid29231989, year = {2018}, author = {Delaney, EK and Hoekstra, HE}, title = {Sexual imprinting and speciation between two Peromyscus species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {274-287}, doi = {10.1111/evo.13409}, pmid = {29231989}, issn = {1558-5646}, abstract = {Sexual isolation, a reproductive barrier, can prevent interbreeding between diverging populations or species. Sexual isolation can have a clear genetic basis; however, it may also result from learned mate preferences that form via sexual imprinting. Here, we demonstrate that two sympatric species of mice-the white-footed mouse (Peromyscus leucopus) and its sister species, the cotton mouse (P. gossypinus)-hybridize only rarely in the wild despite co-occurrence in the same habitat and lack of any measurable intrinsic postzygotic barriers in laboratory crosses. We present evidence that strong conspecific mating preferences in each species result in significant sexual isolation. We find that these preferences are learned in at least one species: P. gossypinus sexually imprints on its parents, but in P. leucopus, additional factors influence mating preferences. Our study demonstrates that sexual imprinting contributes to reproductive isolation that reduces hybridization between otherwise interfertile species, supporting the role for learning in mammalian speciation.}, } @article {pmid29231158, year = {2018}, author = {Oguntoyinbo, FA and Cnockaert, M and Cho, GS and Kabisch, J and Neve, H and Bockelmann, W and Wenning, M and Franz, CMAP and Vandamme, P}, title = {Halomonas nigrificans sp. nov., isolated from cheese.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {371-376}, doi = {10.1099/ijsem.0.002515}, pmid = {29231158}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cheese/*microbiology ; DNA, Bacterial/genetics ; Europe ; *Food Microbiology ; Genes, Bacterial ; Halomonas/*classification/genetics/isolation & purification ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {A Gram-stain-negative, rod-shaped Proteobacteria isolate, MBT G8648T, was obtained from an acid curd cheese called Quargel. The isolate was moderately salt tolerant and motile, with numerous peritrichous flagella. The 16S rRNA gene sequence analysis indicated that the strain belongs to the genus Halomonas, with 98.42 % 16S rRNA gene sequence similarity with Halomonas titanicae BH1T as nearest related neighbour. Further comparative sequence analysis of secA and gyrB genes, as well as physiological and biochemical tests, revealed that this bacterium formed a taxon well-separated from its nearest neighbours and other established Halomonas species. Thus, the strain represents a new species, for which the name Halomonas nigrificans sp. nov. is proposed, with strain MBT G8648T (=LMG 29097T =DSM 105749T) as type strain.}, } @article {pmid29231155, year = {2018}, author = {Zhang, B and Liu, ZQ and Zheng, YG}, title = {Pedobacter quisquiliarum sp. nov., isolated from activated sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {438-442}, doi = {10.1099/ijsem.0.002531}, pmid = {29231155}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Pedobacter/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, rod-shaped, bacterium, C62-2T, was isolated from activated sludge in Fujian Province, China. Phylogenetic analysis of the 16S rRNA gene sequences showed that it was closely related to Pedobacter duraquae WB 2.1-25T (97.92 %), Pedobacter bambusae THG-G118T (97.40 %), Pedobacter cryoconitis A37T (97.37 %) and Pedobacter caeni LMG 22862T (97.3 %). Cells grew aerobically at 20-37 °C (optimum, 30 °C), pH 5.0-8.0 (optimum, pH 7.0) and in the presence of 0-3.0 % (w/v) NaCl. Strain C62-2T contained MK-7 as the major menaquinone and the major polar lipid was phosphatidylethanolamine. The major cellular fatty acids were iso-C15 : 0, summed feature 3 (C16 : 1ω6c, C16 : 1ω7c) and iso-C17 : 0 3-OH. The DNA G+C content was 43.2 mol% (Tm) and DNA-DNA reassociation values were 35.4 % between strain C62-2T and P. duraquae WB 2.1-25T. On the basis of phenotypic, chemotaxonomic and phylogenetic comparisons with the closely related species and DNA-DNA relatedness values, it was concluded that strain C62-2T represents a novel species within the genus Pedobacter, for which the name Pedobacterquisquiliarum sp. nov. is proposed. The type strain is C62-2T (=CGMCC 1.15343T=NBRC 111767T).}, } @article {pmid29230933, year = {2018}, author = {Tapia, P and Fernández-Galilea, M and Robledo, F and Mardones, P and Galgani, JE and Cortés, VA}, title = {Biology and pathological implications of brown adipose tissue: promises and caveats for the control of obesity and its associated complications.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1145-1164}, doi = {10.1111/brv.12389}, pmid = {29230933}, issn = {1469-185X}, abstract = {The discovery of metabolically active brown adipose tissue (BAT) in adult humans has fuelled the research of diverse aspects of this previously neglected tissue. BAT is solely present in mammals and its clearest physiological role is non-shivering thermogenesis, owing to the capacity of brown adipocytes to dissipate metabolic energy as heat. Recently, a number of other possible functions have been proposed, including direct regulation of glucose and lipid homeostasis and the secretion of a number of factors with diverse regulatory actions. Herein, we review recent advances in general biological knowledge of BAT and discuss the possible implications of this tissue in human metabolic health. In particular, we confront the claimed thermogenic potential of BAT for human energy balance and body mass regulation, mostly based on animal studies, with the most recent quantifications of human BAT.}, } @article {pmid29230925, year = {2018}, author = {Matilla, MA}, title = {Novel pressure sensors and bioreporters in the synthetic biology era.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {141-144}, doi = {10.1111/1462-2920.14019}, pmid = {29230925}, issn = {1462-2920}, } @article {pmid29230921, year = {2018}, author = {Linder, HP and Lehmann, CER and Archibald, S and Osborne, CP and Richardson, DM}, title = {Global grass (Poaceae) success underpinned by traits facilitating colonization, persistence and habitat transformation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1125-1144}, doi = {10.1111/brv.12388}, pmid = {29230921}, issn = {1469-185X}, abstract = {Poaceae (the grasses) is arguably the most successful plant family, in terms of its global occurrence in (almost) all ecosystems with angiosperms, its ecological dominance in many ecosystems, and high species richness. We suggest that the success of grasses is best understood in context of their capacity to colonize, persist, and transform environments (the "Viking syndrome"). This results from combining effective long-distance dispersal, efficacious establishment biology, ecological flexibility, resilience to disturbance and the capacity to modify environments by changing the nature of fire and mammalian herbivory. We identify a diverse set of functional traits linked to dispersal, establishment and competitive abilities. Enhanced long-distance dispersal is determined by anemochory, epizoochory and endozoochory and is facilitated via the spikelet (and especially the awned lemma) which functions as the dispersal unit. Establishment success could be a consequence of the precocious embryo and large starch reserves, which may underpin the extremely short generation times in grasses. Post-establishment genetic bottlenecks may be mitigated by wind pollination and the widespread occurrence of polyploidy, in combination with gametic self-incompatibility. The ecological competitiveness of grasses is corroborated by their dominance across the range of environmental extremes tolerated by angiosperms, facilitated by both C3 and C4 photosynthesis, well-developed frost tolerance in several clades, and a sympodial growth form that enabled the evolution of both annual and long-lived life forms. Finally, absence of investment in wood (except in bamboos), and the presence of persistent buds at or below ground level, provides tolerance of repeated defoliation (whether by fire, frost, drought or herbivores). Biotic modification of environments via feedbacks with herbivory or fire reinforce grass dominance leading to open ecosystems. Grasses can be both palatable and productive, fostering high biomass and diversity of mammalian herbivores. Many grasses have a suite of architectural and functional traits that facilitate frequent fire, including a tufted growth form, and tannin-like substances in leaves which slow decomposition. We mapped these traits over the phylogeny of the Poales, spanning the grasses and their relatives, and demonstrated the accumulation of traits since monocots originated in the mid-Cretaceous. Although the sympodial growth form is a monocot trait, tillering resulting in the tufted growth form most likely evolved within the grasses. Similarly, although an ovary apparently constructed of a single carpel evolved in the most recent grass ancestor, spikelets and the awned lemma dispersal units evolved within the grasses. Frost tolerance and C4 photosynthesis evolved relatively late (late Palaeogene), and the last significant trait to evolve was probably the production of tannins, associated with pyrophytic savannas. This fits palaeobotanical data, suggesting several phases in the grass success story: from a late Cretaceous origin, to occasional tropical grassland patches in the later Palaeogene, to extensive C3 grassy woodlands in the early-middle Miocene, to the dramatic expansion of the tropical C4 grass savannas and grasslands in the Pliocene, and the C3 steppe grasslands during the Pleistocene glacial periods. Modern grasslands depend heavily on strongly seasonal climates, making them sensitive to climate change.}, } @article {pmid29230029, year = {2018}, author = {Mullon, C and Keller, L and Lehmann, L}, title = {Publisher Correction: Social polymorphism is favoured by the co-evolution of dispersal with social behaviour.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {197}, doi = {10.1038/s41559-017-0439-5}, pmid = {29230029}, issn = {2397-334X}, abstract = {Owing to a technical error, some text was missing in the originally published version of this Article. In the last paragraph of the Discussion section, the second sentence should have read "Yet, the selection that associates dispersal and social behaviour in our model will influence evolution under most ecological settings because it depends only on kin structure, which, due to limited dispersal and the spatial scale of social interactions, is ubiquitous in nature47." This error has now been corrected in all versions of the Article.}, } @article {pmid29230028, year = {2018}, author = {Jansen, J and Hill, NA and Dunstan, PK and McKinlay, J and Sumner, MD and Post, AL and Eléaume, MP and Armand, LK and Warnock, JP and Galton-Fenzi, BK and Johnson, CR}, title = {Abundance and richness of key Antarctic seafloor fauna correlates with modelled food availability.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {71-80}, doi = {10.1038/s41559-017-0392-3}, pmid = {29230028}, issn = {2397-334X}, mesh = {Animals ; Antarctic Regions ; Aquatic Organisms/physiology ; *Biodiversity ; Diatoms ; *Food Chain ; Invertebrates/*physiology ; Models, Biological ; Oceans and Seas ; Seawater/chemistry ; }, abstract = {Most seafloor communities at depths below the photosynthesis zone rely on food that sinks through the water column. However, the nature and strength of this pelagic-benthic coupling and its influence on the structure and diversity of seafloor communities is unclear, especially around Antarctica where ecological data are sparse. Here we show that the strength of pelagic-benthic coupling along the East Antarctic shelf depends on both physical processes and the types of benthic organisms considered. In an approach based on modelling food availability, we combine remotely sensed sea-surface chlorophyll-a, a regional ocean model and diatom abundances from sediment grabs with particle tracking and show that fluctuating seabed currents are crucial in the redistribution of surface productivity at the seafloor. The estimated availability of suspended food near the seafloor correlates strongly with the abundance of benthic suspension feeders, while the deposition of food particles correlates with decreasing suspension feeder richness and more abundant deposit feeders. The modelling framework, which can be modified for other regions, has broad applications in conservation and management, as it enables spatial predictions of key components of seafloor biodiversity over vast regions around Antarctica.}, } @article {pmid29230027, year = {2018}, author = {Feigin, CY and Newton, AH and Doronina, L and Schmitz, J and Hipsley, CA and Mitchell, KJ and Gower, G and Llamas, B and Soubrier, J and Heider, TN and Menzies, BR and Cooper, A and O'Neill, RJ and Pask, AJ}, title = {Genome of the Tasmanian tiger provides insights into the evolution and demography of an extinct marsupial carnivore.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {182-192}, doi = {10.1038/s41559-017-0417-y}, pmid = {29230027}, issn = {2397-334X}, mesh = {Animals ; Australia ; Demography ; *Evolution, Molecular ; *Genome ; Marsupialia/*genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The Tasmanian tiger or thylacine (Thylacinus cynocephalus) was the largest carnivorous Australian marsupial to survive into the modern era. Despite last sharing a common ancestor with the eutherian canids ~160 million years ago, their phenotypic resemblance is considered the most striking example of convergent evolution in mammals. The last known thylacine died in captivity in 1936 and many aspects of the evolutionary history of this unique marsupial apex predator remain unknown. Here we have sequenced the genome of a preserved thylacine pouch young specimen to clarify the phylogenetic position of the thylacine within the carnivorous marsupials, reconstruct its historical demography and examine the genetic basis of its convergence with canids. Retroposon insertion patterns placed the thylacine as the basal lineage in Dasyuromorphia and suggest incomplete lineage sorting in early dasyuromorphs. Demographic analysis indicated a long-term decline in genetic diversity starting well before the arrival of humans in Australia. In spite of their extraordinary phenotypic convergence, comparative genomic analyses demonstrated that amino acid homoplasies between the thylacine and canids are largely consistent with neutral evolution. Furthermore, the genes and pathways targeted by positive selection differ markedly between these species. Together, these findings support models of adaptive convergence driven primarily by cis-regulatory evolution.}, } @article {pmid29230026, year = {2018}, author = {Monchamp, ME and Spaak, P and Domaizon, I and Dubois, N and Bouffard, D and Pomati, F}, title = {Homogenization of lake cyanobacterial communities over a century of climate change and eutrophication.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {317-324}, doi = {10.1038/s41559-017-0407-0}, pmid = {29230026}, issn = {2397-334X}, abstract = {Human impacts on biodiversity are well recognized, but uncertainties remain regarding patterns of diversity change at different spatial and temporal scales. Changes in microbial assemblages are, in particular, not well understood, partly due to the lack of community composition data over relevant scales of space and time. Here, we investigate biodiversity patterns in cyanobacterial assemblages over one century of eutrophication and climate change by sequencing DNA preserved in the sediments of ten European peri-Alpine lakes. We found species losses and gains at the lake scale, while species richness increased at the regional scale over approximately the past 100 years. Our data show a clear signal for beta diversity loss, with the composition and phylogenetic structure of assemblages becoming more similar across sites in the most recent decades, as have the general environmental conditions in and around the lakes. We attribute patterns of change in community composition to raised temperatures affecting the strength of the thermal stratification and, as a consequence, nutrient fluctuations, which favoured cyanobacterial taxa able to regulate buoyancy. Our results reinforce previous reports of human-induced homogenization of natural communities and reveal how potentially toxic and bloom-forming cyanobacteria have widened their geographic distribution in the European temperate region.}, } @article {pmid29230025, year = {2018}, author = {Bischof, R and Bonenfant, C and Rivrud, IM and Zedrosser, A and Friebe, A and Coulson, T and Mysterud, A and Swenson, JE}, title = {Regulated hunting re-shapes the life history of brown bears.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {116-123}, doi = {10.1038/s41559-017-0400-7}, pmid = {29230025}, issn = {2397-334X}, mesh = {Animals ; *Conservation of Natural Resources ; Female ; *Life History Traits ; *Longevity ; Male ; Population Dynamics ; *Reproduction ; Sweden ; Ursidae/*physiology ; }, abstract = {Management of large carnivores is among the most controversial topics in natural resource administration. Regulated hunting is a centrepiece of many carnivore management programmes and, although a number of hunting effects on population dynamics, body-size distributions and life history in other wildlife have been observed, its effects on life history and demography of large carnivores remain poorly documented. We report results from a 30-year study of brown bears (Ursus arctos) analysed using an integrated hierarchical approach. Our study revealed that regulated hunting has severely disrupted the interplay between age-specific survival and environmental factors, altered the consequences of reproductive strategies, and changed reproductive values and life expectancy in a population of the world's largest terrestrial carnivore. Protection and sustainable management have led to numerical recovery of several populations of large carnivores, but managers and policymakers should be aware of the extent to which regulated hunting may be influencing vital rates, thereby reshaping the life history of apex predators.}, } @article {pmid29230024, year = {2018}, author = {Aleman, JC and Jarzyna, MA and Staver, AC}, title = {Forest extent and deforestation in tropical Africa since 1900.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {26-33}, doi = {10.1038/s41559-017-0406-1}, pmid = {29230024}, issn = {2397-334X}, mesh = {Africa South of the Sahara ; *Carbon Cycle ; *Conservation of Natural Resources ; *Forests ; Tropical Climate ; }, abstract = {Accurate estimates of historical forest extent and associated deforestation rates are crucial for quantifying tropical carbon cycles and formulating conservation policy. In Africa, data-driven estimates of historical closed-canopy forest extent and deforestation at the continental scale are lacking, and existing modelled estimates diverge substantially. Here, we synthesize available palaeo-proxies and historical maps to reconstruct forest extent in tropical Africa around 1900, when European colonization accelerated markedly, and compare these historical estimates with modern forest extent to estimate deforestation. We find that forests were less extensive in 1900 than bioclimatic models predict. Resultantly, across tropical Africa, ~ 21.7% of forests have been deforested, yielding substantially slower deforestation than previous estimates (35-55%). However, deforestation was heterogeneous: West and East African forests have undergone almost complete decline (~ 83.3 and 93.0%, respectively), while Central African forests have expanded at the expense of savannahs (~ 1.4% net forest expansion, with ~ 135,270 km2 of savannahs encroached). These results suggest that climate alone does not determine savannah and forest distributions and that many savannahs hitherto considered to be degraded forests are instead relatively old. These data-driven reconstructions of historical biome distributions will inform tropical carbon cycle estimates, carbon mitigation initiatives and conservation planning in both forest and savannah systems.}, } @article {pmid29229984, year = {2018}, author = {Schwartzentruber, J and Foskolou, S and Kilpinen, H and Rodrigues, J and Alasoo, K and Knights, AJ and Patel, M and Goncalves, A and Ferreira, R and Benn, CL and Wilbrey, A and Bictash, M and Impey, E and Cao, L and Lainez, S and Loucif, AJ and Whiting, PJ and Gutteridge, A and Gaffney, DJ and , }, title = {Molecular and functional variation in iPSC-derived sensory neurons.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {54-61}, pmid = {29229984}, issn = {1546-1718}, support = {//Wellcome Trust/United Kingdom ; 098051//Wellcome Trust/United Kingdom ; 098503//Wellcome Trust/United Kingdom ; }, abstract = {Induced pluripotent stem cells (iPSCs), and cells derived from them, have become key tools for modeling biological processes, particularly in cell types that are difficult to obtain from living donors. Here we present a map of regulatory variants in iPSC-derived neurons, based on 123 differentiations of iPSCs to a sensory neuronal fate. Gene expression was more variable across cultures than in primary dorsal root ganglion, particularly for genes related to nervous system development. Using single-cell RNA-sequencing, we found that the number of neuronal versus contaminating cells was influenced by iPSC culture conditions before differentiation. Despite high differentiation-induced variability, our allele-specific method detected thousands of quantitative trait loci (QTLs) that influenced gene expression, chromatin accessibility, and RNA splicing. On the basis of these detected QTLs, we estimate that recall-by-genotype studies that use iPSC-derived cells will require cells from at least 20-80 individuals to detect the effects of regulatory variants with moderately large effect sizes.}, } @article {pmid29229983, year = {2018}, author = {Li, YI and Knowles, DA and Humphrey, J and Barbeira, AN and Dickinson, SP and Im, HK and Pritchard, JK}, title = {Annotation-free quantification of RNA splicing using LeafCutter.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {151-158}, pmid = {29229983}, issn = {1546-1718}, support = {P30 DK020595/DK/NIDDK NIH HHS/United States ; R01 HG008140/HG/NHGRI NIH HHS/United States ; R01 MH107666/MH/NIMH NIH HHS/United States ; U01 HG009431/HG/NHGRI NIH HHS/United States ; }, abstract = {The excision of introns from pre-mRNA is an essential step in mRNA processing. We developed LeafCutter to study sample and population variation in intron splicing. LeafCutter identifies variable splicing events from short-read RNA-seq data and finds events of high complexity. Our approach obviates the need for transcript annotations and circumvents the challenges in estimating relative isoform or exon usage in complex splicing events. LeafCutter can be used both to detect differential splicing between sample groups and to map splicing quantitative trait loci (sQTLs). Compared with contemporary methods, our approach identified 1.4-2.1 times more sQTLs, many of which helped us ascribe molecular effects to disease-associated variants. Transcriptome-wide associations between LeafCutter intron quantifications and 40 complex traits increased the number of associated disease genes at a 5% false discovery rate by an average of 2.1-fold compared with that detected through the use of gene expression levels alone. LeafCutter is fast, scalable, easy to use, and available online.}, } @article {pmid29229857, year = {2018}, author = {Carlson, KM and Heilmayr, R and Gibbs, HK and Noojipady, P and Burns, DN and Morton, DC and Walker, NF and Paoli, GD and Kremen, C}, title = {Effect of oil palm sustainability certification on deforestation and fire in Indonesia.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {121-126}, pmid = {29229857}, issn = {1091-6490}, mesh = {*Conservation of Natural Resources ; *Crop Production ; Indonesia ; Magnoliopsida/*growth & development ; *Palm Oil ; *Wildfires ; }, abstract = {Many major corporations and countries have made commitments to purchase or produce only "sustainable" palm oil, a commodity responsible for substantial tropical forest loss. Sustainability certification is the tool most used to fulfill these procurement policies, and around 20% of global palm oil production was certified by the Roundtable on Sustainable Palm Oil (RSPO) in 2017. However, the effect of certification on deforestation in oil palm plantations remains unclear. Here, we use a comprehensive dataset of RSPO-certified and noncertified oil palm plantations (∼188,000 km2) in Indonesia, the leading producer of palm oil, as well as annual remotely sensed metrics of tree cover loss and fire occurrence, to evaluate the impact of certification on deforestation and fire from 2001 to 2015. While forest loss and fire continued after RSPO certification, certified palm oil was associated with reduced deforestation. Certification lowered deforestation by 33% from a counterfactual of 9.8 to 6.6% y-1 Nevertheless, most plantations contained little residual forest when they received certification. As a result, by 2015, certified areas held less than 1% of forests remaining within Indonesian oil palm plantations. Moreover, certification had no causal impact on forest loss in peatlands or active fire detection rates. Broader adoption of certification in forested regions, strict requirements to avoid all peat, and routine monitoring of clearly defined forest cover loss in certified and RSPO member-held plantations appear necessary if the RSPO is to yield conservation and climate benefits from reductions in tropical deforestation.}, } @article {pmid29229842, year = {2018}, author = {Bogaert, AF and Skorska, MN and Wang, C and Gabrie, J and MacNeil, AJ and Hoffarth, MR and VanderLaan, DP and Zucker, KJ and Blanchard, R}, title = {Male homosexuality and maternal immune responsivity to the Y-linked protein NLGN4Y.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {302-306}, pmid = {29229842}, issn = {1091-6490}, mesh = {Adult ; Antibodies/immunology ; Birth Order ; Brain/immunology/metabolism ; Cell Adhesion Molecules, Neuronal/genetics/*immunology/metabolism ; Female ; Heterosexuality ; Homosexuality ; *Homosexuality, Male ; Humans ; Male ; Mothers ; *Sexual Behavior ; *Siblings ; }, abstract = {We conducted a direct test of an immunological explanation of the finding that gay men have a greater number of older brothers than do heterosexual men. This explanation posits that some mothers develop antibodies against a Y-linked protein important in male brain development, and that this effect becomes increasingly likely with each male gestation, altering brain structures underlying sexual orientation in their later-born sons. Immune assays targeting two Y-linked proteins important in brain development-protocadherin 11 Y-linked (PCDH11Y) and neuroligin 4 Y-linked (NLGN4Y; isoforms 1 and 2)-were developed. Plasma from mothers of sons, about half of whom had a gay son, along with additional controls (women with no sons, men) was analyzed for male protein-specific antibodies. Results indicated women had significantly higher anti-NLGN4Y levels than men. In addition, after statistically controlling for number of pregnancies, mothers of gay sons, particularly those with older brothers, had significantly higher anti-NLGN4Y levels than did the control samples of women, including mothers of heterosexual sons. The results suggest an association between a maternal immune response to NLGN4Y and subsequent sexual orientation in male offspring.}, } @article {pmid29229782, year = {2018}, author = {Nagasawa, M and Spits, H and Ros, XR}, title = {Innate Lymphoid Cells (ILCs): Cytokine Hubs Regulating Immunity and Tissue Homeostasis.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, doi = {10.1101/cshperspect.a030304}, pmid = {29229782}, issn = {1943-0264}, abstract = {Innate lymphoid cells (ILCs) have emerged as an expanding family of effector cells particularly enriched in the mucosal barriers. ILCs are promptly activated by stress signals and multiple epithelial- and myeloid-cell-derived cytokines. In response, ILCs rapidly secrete effector cytokines, which allow them to survey and maintain the mucosal integrity. Uncontrolled action of ILCs might contribute to tissue damage, chronic inflammation, metabolic diseases, autoimmunity, and cancer. Here we discuss the recent advances in our understanding of the cytokine network that modulate ILC immune responses: stimulating cytokines, signature cytokines secreted by ILC subsets, autocrine cytokines, and cytokines that induce cell plasticity.}, } @article {pmid29229651, year = {2018}, author = {Wahlund, JE and Morooka, MW and Hadid, LZ and Persoon, AM and Farrell, WM and Gurnett, DA and Hospodarsky, G and Kurth, WS and Ye, SY and Andrews, DJ and Edberg, NJT and Eriksson, AI and Vigren, E}, title = {In situ measurements of Saturn's ionosphere show that it is dynamic and interacts with the rings.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {66-68}, doi = {10.1126/science.aao4134}, pmid = {29229651}, issn = {1095-9203}, abstract = {The ionized upper layer of Saturn's atmosphere, its ionosphere, provides a closure of currents mediated by the magnetic field to other electrically charged regions (for example, rings) and hosts ion-molecule chemistry. In 2017, the Cassini spacecraft passed inside the planet's rings, allowing in situ measurements of the ionosphere. The Radio and Plasma Wave Science instrument detected a cold, dense, and dynamic ionosphere at Saturn that interacts with the rings. Plasma densities reached up to 1000 cubic centimeters, and electron temperatures were below 1160 kelvin near closest approach. The density varied between orbits by up to two orders of magnitude. Saturn's A- and B-rings cast a shadow on the planet that reduced ionization in the upper atmosphere, causing a north-south asymmetry.}, } @article {pmid29229488, year = {2018}, author = {Milla, L and van Nieukerken, EJ and Vijverberg, R and Doorenweerd, C and Wilcox, SA and Halsey, M and Young, DA and Jones, TM and Kallies, A and Hilton, DJ}, title = {A preliminary molecular phylogeny of shield-bearer moths (Lepidoptera: Adeloidea: Heliozelidae) highlights rich undescribed diversity.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {129-143}, doi = {10.1016/j.ympev.2017.12.004}, pmid = {29229488}, issn = {1095-9513}, mesh = {Animals ; Biological Evolution ; DNA/chemistry/isolation & purification/metabolism ; Databases, Genetic ; Electron Transport Complex IV/chemistry/classification/genetics ; Genes, Mitochondrial ; Genetic Variation ; High-Throughput Nucleotide Sequencing ; Histones/classification/genetics/metabolism ; Insect Proteins/classification/genetics/metabolism ; Moths/*classification/genetics ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Heliozelidae are a widespread, evolutionarily early diverging family of small, day-flying monotrysian moths, for which a comprehensive phylogeny is lacking. We generated the first molecular phylogeny of the family using DNA sequences of two mitochondrial genes (COI and COII) and two nuclear genes (H3 and 28S) from 130 Heliozelidae specimens, including eight of the twelve known genera: Antispila, Antispilina, Coptodisca, Heliozela, Holocacista, Hoplophanes, Pseliastis, and Tyriozela. Our results provide strong support for five major Heliozelidae clades: (i) a large widespread clade containing the leaf-mining genera Antispilina, Coptodisca and Holocacista and some species of Antispila, (ii) a clade containing most of the described Antispila, (iii) a clade containing the leaf-mining genus Heliozela and the monotypic genus Tyriozela, (iv) an Australian clade containing Pseliastis and (v) an Australian clade containing Hoplophanes. Each clade includes several new species and potentially new genera. Collectively, our data uncover a rich and undescribed diversity that appears to be especially prevalent in Australia. Our work highlights the need for a major taxonomic revision of the family and for generating a robust molecular phylogeny using multi-gene approaches in order to resolve the relationships among clades.}, } @article {pmid29229250, year = {2018}, author = {Afouda, BA and Lynch, AT and de Paiva Alves, E and Hoppler, S}, title = {Genome-wide transcriptomics analysis identifies sox7 and sox18 as specifically regulated by gata4 in cardiomyogenesis.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {108-120}, pmid = {29229250}, issn = {1095-564X}, support = {PG/13/23/30080//British Heart Foundation/United Kingdom ; BB/M001695/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; GATA4 Transcription Factor/genetics/*metabolism ; Gene Expression Profiling ; Genome-Wide Association Study ; Heart/*embryology ; Mice ; Mouse Embryonic Stem Cells/cytology/metabolism ; Myocytes, Cardiac/cytology/*metabolism ; Organogenesis/*physiology ; SOXF Transcription Factors/*biosynthesis/genetics ; Xenopus Proteins/*biosynthesis/genetics/*metabolism ; Xenopus laevis ; }, abstract = {The transcription factors GATA4, GATA5 and GATA6 are important regulators of heart muscle differentiation (cardiomyogenesis), which function in a partially redundant manner. We identified genes specifically regulated by individual cardiogenic GATA factors in a genome-wide transcriptomics analysis. The genes regulated by gata4 are particularly interesting because GATA4 is able to induce differentiation of beating cardiomyocytes in Xenopus and in mammalian systems. Among the specifically gata4-regulated transcripts we identified two SoxF family members, sox7 and sox18. Experimental reinstatement of gata4 restores sox7 and sox18 expression, and loss of cardiomyocyte differentiation due to gata4 knockdown is partially restored by reinstating sox7 or sox18 expression, while (as previously reported) knockdown of sox7 or sox18 interferes with heart muscle formation. In order to test for conservation in mammalian cardiomyogenesis, we confirmed in mouse embryonic stem cells (ESCs) undergoing cardiomyogenesis that knockdown of Gata4 leads to reduced Sox7 (and Sox18) expression and that Gata4 is also uniquely capable of promptly inducing Sox7 expression. Taken together, we identify an important and conserved gene regulatory axis from gata4 to the SoxF paralogs sox7 and sox18 and further to heart muscle cell differentiation.}, } @article {pmid29229233, year = {2018}, author = {Tjaden, NB and Caminade, C and Beierkuhnlein, C and Thomas, SM}, title = {Mosquito-Borne Diseases: Advances in Modelling Climate-Change Impacts.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {227-245}, doi = {10.1016/j.pt.2017.11.006}, pmid = {29229233}, issn = {1471-5007}, support = {MR/M0501633/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; *Climate Change ; Communicable Diseases/*epidemiology/transmission ; Humans ; *Models, Biological ; Mosquito Vectors/*physiology/virology ; Risk Assessment/*trends ; }, abstract = {Vector-borne diseases are on the rise globally. As the consequences of climate change are becoming evident, climate-based models of disease risk are of growing importance. Here, we review the current state-of-the-art in both mechanistic and correlative disease modelling, the data driving these models, the vectors and diseases covered, and climate models applied to assess future risk. We find that modelling techniques have advanced considerably, especially in terms of using ensembles of climate models and scenarios. Effects of extreme events, precipitation regimes, and seasonality on diseases are still poorly studied. Thorough validation of models is still a challenge and is complicated by a lack of field and laboratory data. On a larger scale, the main challenges today lie in cross-disciplinary and cross-sectoral transfer of data and methods.}, } @article {pmid29228354, year = {2018}, author = {Radujkovic, D and Verbruggen, E and Sigurdsson, BD and Leblans, NIW and Janssens, IA and Vicca, S and Weedon, JT}, title = {Prolonged exposure does not increase soil microbial community compositional response to warming along geothermal gradients.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix174}, pmid = {29228354}, issn = {1574-6941}, abstract = {Global change is expected to affect soil microbial communities through their responsiveness to temperature. It has been proposed that prolonged exposure to elevated temperatures may lead to progressively larger effects on soil microbial community composition. However, due to the relatively short-term nature of most warming experiments, this idea has been challenging to evaluate. The present study took the advantage of natural geothermal gradients (from +1°C to +19°C above ambient) in two subarctic grasslands to test the hypothesis that long-term exposure (>50 years) intensifies the effect of warming on microbial community composition compared to short-term exposure (5-7 years). Community profiles from amplicon sequencing of bacterial and fungal rRNA genes did not support this hypothesis: significant changes relative to ambient were observed only starting from the warming intensity of +9°C in the long term and +7°C/+3°C in the short term, for bacteria and fungi, respectively. Our results suggest that microbial communities in high-latitude grasslands will not undergo lasting shifts in community composition under the warming predicted for the coming 100 years (+2.2°C to +8.3°C).}, } @article {pmid29228342, year = {2018}, author = {Perez, R and Wörmer, L and Sass, P and Maldener, I}, title = {A highly asynchronous developmental program triggered during germination of dormant akinetes of filamentous diazotrophic cyanobacteria.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix131}, pmid = {29228342}, issn = {1574-6941}, abstract = {Germination of akinetes of filamentous heterocyst-forming cyanobacteria of the order Nostocales is an essential process that ensures survival and recolonization after long periods of unfavorable conditions, as desiccation, cold and low light. We studied the morphological, physiological and metabolic changes that occur during germination of akinetes in two model species of cell differentiation, Anabaena variabilis ATCC 29413 and Nostoc punctiforme ATCC 29133, which live in different habitats. We characterized the akinete envelopes and showed their similarity to envelopes of N2-fixing heterocysts. Akinete germination started inside the envelopes and was dependent on light intensity but independent of nitrogen supply. During the germination of A. variabilis akinetes, cell division and heterocyst differentiation were highly accelerated. The energy for cell division was initially supplied by respiration of glycogen and subsequently by photosynthesis. By contrast, during germination of N. punctiforme akinetes, cell division and heterocyst differentiation were slow. During the initial 15-20 h, N. punctiforme akinetes increased in volume and some burst. Only then did intact akinetes start to divide and fully germinate, possibly fueled by nutrients released from dead akinetes. The different strategies used by these different cyanobacteria allow successful germination of dormant cells and recolonization under favorable conditions.}, } @article {pmid29228270, year = {2018}, author = {Yitbarek, A and Weese, JS and Alkie, TN and Parkinson, J and Sharif, S}, title = {Influenza A virus subtype H9N2 infection disrupts the composition of intestinal microbiota of chickens.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix165}, pmid = {29228270}, issn = {1574-6941}, abstract = {The impact of low pathogenic influenza viruses such as subtype H9N2, which infect the respiratory and the gastrointestinal tracts of chickens, on microbial composition are not known. Twenty-day-old specific pathogen-free chickens were assigned to two treatment groups, control (uninfected) and H9N2-infected (challenged via the oral-nasal route). Fecal genomic DNA was extracted, and the V3-V4 regions of the 16S rRNA gene were sequenced using the Illumina Miseq® platform. Sequences were curated using Mothur as described in the MiSeq SOP. Infection of chickens with H9N2 resulted in an increase in phylum Proteobacteria, and differential enrichment with the genera Vampirovibrio, Pseudoflavonifractor, Ruminococcus, Clostridium cluster XIVb and Isobaculum while control chickens were differentially enriched with genera Novosphingobium, Sphingomonas, Bradyrhizobium and Bifidobacterium. Analysis of pre- and post-H9N2 infection of the same chickens showed that, before infection, the fecal microbiota was characterized by Lachnospiracea and Ruminococcaceae family and the genera Clostridium sensu stricto, Roseburia and Lachnospiraceae incertae sedis. However, post-H9N2 infection, class Deltaproteobacteria, orders Clostridiales and Bacteroidiales and the genus Alistipes were differentially enriched. Findings from the current study show that influenza virus infection in chickens results in the shift of the gut microbiota, and the disruption of the host-microbial homeostasis in the gut might be one of the mechanisms by which influenza virus infection is established in chickens.}, } @article {pmid29228264, year = {2018}, author = {Porter, SS and Faber-Hammond, JJ and Friesen, ML}, title = {Co-invading symbiotic mutualists of Medicago polymorpha retain high ancestral diversity and contain diverse accessory genomes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix168}, pmid = {29228264}, issn = {1574-6941}, abstract = {Exotic, invasive plants and animals can wreak havoc on ecosystems by displacing natives and altering environmental conditions. However, much less is known about the identities or evolutionary dynamics of the symbiotic microbes that accompany invasive species. Most leguminous plants rely upon symbiotic rhizobium bacteria to fix nitrogen and are incapable of colonizing areas devoid of compatible rhizobia. We compare the genomes of symbiotic rhizobia in a portion of the legume's invaded range with those of the rhizobium symbionts from across the legume's native range. We show that in an area of California the legume Medicago polymorpha has invaded, its Ensifer medicae symbionts: (i) exhibit genome-wide patterns of relatedness that together with historical evidence support host-symbiont co-invasion from Europe into California, (ii) exhibit population genomic patterns consistent with the introduction of the majority of deep diversity from the native range, rather than a genetic bottleneck during colonization of California and (iii) harbor a large set of accessory genes uniquely enriched in binding functions, which could play a role in habitat invasion. Examining microbial symbiont genome dynamics during biological invasions is critical for assessing host-symbiont co-invasions whereby microbial symbiont range expansion underlies plant and animal invasions.}, } @article {pmid29228258, year = {2018}, author = {, }, title = {Reply to the article 'In defense of Bacillus thuringiensis, the safest and most successful microbial insecticide available to humanity-a response to EFSA'.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix171}, pmid = {29228258}, issn = {1574-6941}, mesh = {*Bacillus thuringiensis ; *Insecticides ; }, } @article {pmid29228257, year = {2018}, author = {David, H and Laza-Martínez, A and Kromkamp, JC and Orive, E}, title = {Physiological response of Prorocentrum lima (Dinophyceae) to varying light intensities.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix166}, pmid = {29228257}, issn = {1574-6941}, abstract = {The benthic dinoflagellate Prorocentrum lima is among the most common toxic morphospecies with a cosmopolitan distribution. This study explored if strains from different environments and different morphotypes, isolated from three locations in the Atlantic Iberian Peninsula and two from the Mediterranean Sea, showed different responses to varying light regimes, after confirming that all strains belonged to the same ribotype. Growth rates and photosynthetic parameters such as Fo, Fv/Fm, and rETRmax were analysed with a Coulter counter, a water-PAM and a fast repetition rate fluorometer. The photosynthetic properties were investigated in a high light stress experiment using strains acclimated to low light (LL) and high light (HL). The highest growth rate was 0.23 day-1 at 80 and 100 μmol photons m-2 s-1 for strains Dn150EHU and Dn60EHU, originated from different locations. Under control conditions (18°C and 90 μmol photons m-2 s-1), growth rate was on average 0.10 day-1. The HL stress exposure induced photodamage to all strains and the recovery period was not sufficiently long for full recovery of Fv/Fm. However, cells acclimated to HL showed a better recovery than the LL acclimated ones. Furthermore, some assumptions are discussed in relation to strains' original location.}, } @article {pmid29228256, year = {2018}, author = {Sommers, P and Darcy, JL and Gendron, EMS and Stanish, LF and Bagshaw, EA and Porazinska, DL and Schmidt, SK}, title = {Diversity patterns of microbial eukaryotes mirror those of bacteria in Antarctic cryoconite holes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix167}, pmid = {29228256}, issn = {1574-6941}, abstract = {Ice-lidded cryoconite holes on glaciers in the Taylor Valley, Antarctica, provide a unique system of natural mesocosms for studying community structure and assembly. We used high-throughput DNA sequencing to characterize both microbial eukaryotic communities and bacterial communities within cryoconite holes across three glaciers to study similarities in their spatial patterns. We expected that the alpha (phylogenetic diversity) and beta (pairwise community dissimilarity) diversity patterns of eukaryotes in cryoconite holes would be related to those of bacteria, and that they would be related to the biogeochemical gradient within the Taylor Valley. We found that eukaryotic alpha and beta diversity were strongly related to those of bacteria across scales ranging from 140 m to 41 km apart. Alpha diversity of both was significantly related to position in the valley and surface area of the cryoconite hole, with pH also significantly correlated with the eukaryotic diversity. Beta diversity for both bacteria and eukaryotes was significantly related to position in the valley, with bacterial beta diversity also related to nitrate. These results are consistent with transport of sediments onto glaciers occurring primarily at local scales relative to the size of the valley, thus creating feedbacks in local chemistry and diversity.}, } @article {pmid29228248, year = {2018}, author = {Kalenyak, K and Isaiah, A and Heilmann, RM and Suchodolski, JS and Burgener, IA}, title = {Comparison of the intestinal mucosal microbiota in dogs diagnosed with idiopathic inflammatory bowel disease and dogs with food-responsive diarrhea before and after treatment.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix173}, pmid = {29228248}, issn = {1574-6941}, abstract = {We report the first study to evaluate the intestinal mucosal microbiota of dogs with inflammatory bowel disease (IBD) and dogs with food-responsive diarrhea (FRD) before and after treatment. It was hypothesized that differences in the microbial composition exist between both disease groups and within groups pre- vs. post-treatment. Duodenal and colonic biopsies were obtained endoscopically from 24 dogs (15 FRD, 9 IBD) before and after treatment. The intestinal microbiota was evaluated by Illumina sequencing of the bacterial 16S rRNA gene. The global bacterial composition did not differ between IBD and FRD dogs, nor between treatment status. However, several bacterial taxa showed a difference in abundance. Comparing disease groups, an unclassified genus of Neisseriaceae was abundant in the duodenum in the IBD group, whereas Bilophila occurred more frequently in the duodenum and Burkholderia in the colon of FRD dogs. Comparing the microbiota pre- and post-treatment revealed Enterococcus, Corynebacterium and Proteobacteria to be enriched in the duodenum of FRD dogs pre-treatment, while Bacteroides was abundant in the colon post-treatment. In dogs with IBD, Bacteroides also reached significant abundance in the colon post-treatment. In conclusion, some differences in individual bacterial taxa were identified between IBD and FRD dogs and between treatment status.}, } @article {pmid29228244, year = {2018}, author = {Cleary, DFR and Polónia, ARM and de Voogd, NJ}, title = {Prokaryote composition and predicted metagenomic content of two Cinachyrella Morphospecies and water from West Papuan Marine Lakes.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix175}, pmid = {29228244}, issn = {1574-6941}, abstract = {Certain sponge species are difficult to identify using classical taxonomic characters, and other techniques are often necessary. Here we used 454-pyrosequencing of the 16S rRNA gene to investigate bacterial and archaeal communities of two distinct Cinachyrella morphospecies collected from two Indonesian marine lakes with differing degrees of connection to the surrounding sea. Our main goal was to assess whether these morphospecies hosted distinct bacterial and archaeal communities and to what extent these differed from those found in lake water. A recently developed bioinformatic tool (PICRUSt) was used to predict metagenomic gene content of the studied communities. Compositionally, sponge samples clustered according to morphospecies as opposed to marine lake indicating that each morphospecies hosted distinct bacterial and archaeal communities. There were, however, also differences in higher taxon abundance among lakes. In the less connected lake, for example, both Cinachyrella morphospecies had higher levels of the order Synechococcales. With respect to metabolic gene content, although there were pronounced differences in predicted enrichment between both morphospecies, both were putatively enriched for KOs involved in pathways related to stress response, energy metabolism, environmental information processing and the production of secondary metabolites compared to prokaryote communities in water. These morphospecies may thus prove to be interesting sources of novel compounds of potential pharmaceutical and/or biotechnological importance.}, } @article {pmid29228229, year = {2018}, author = {Kottara, A and Hall, JPJ and Harrison, E and Brockhurst, MA}, title = {Variable plasmid fitness effects and mobile genetic element dynamics across Pseudomonas species.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, pmid = {29228229}, issn = {1574-6941}, support = {311490//European Research Council/International ; }, abstract = {Mobile genetic elements (MGE) such as plasmids and transposons mobilise genes within and between species, playing a crucial role in bacterial evolution via horizontal gene transfer (HGT). Currently, we lack data on variation in MGE dynamics across bacterial host species. We tracked the dynamics of a large conjugative plasmid, pQBR103, and its Tn5042 mercury resistance transposon, in five diverse Pseudomonas species in environments with and without mercury selection. Plasmid fitness effects and stability varied extensively between host species and environments, as did the propensity for chromosomal capture of the Tn5042 mercury resistance transposon associated with loss of the plasmid. Whereas Pseudomonas fluorescens and Pseudomonas savastanoi stably maintained the plasmid in both environments, the plasmid was highly unstable in Pseudomonas aeruginosa and Pseudomonas putida, where plasmid-free genotypes with Tn5042 captured to the chromosome invaded to higher frequency under mercury selection. These data confirm that plasmid stability is dependent upon the specific genetic interaction of the plasmid and host chromosome rather than being a property of plasmids alone, and moreover imply that MGE dynamics in diverse natural communities are likely to be complex and driven by a subset of species capable of stably maintaining plasmids that would then act as hubs of HGT.}, } @article {pmid29228192, year = {2018}, author = {Lueder, U and Druschel, G and Emerson, D and Kappler, A and Schmidt, C}, title = {Quantitative analysis of O2 and Fe2+ profiles in gradient tubes for cultivation of microaerophilic Iron(II)-oxidizing bacteria.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix177}, pmid = {29228192}, issn = {1574-6941}, abstract = {The classical approach for the cultivation of neutrophilic microaerophilic Fe(II)-oxidizing bacteria is agar-based gradient tubes where these bacteria find optimal growth conditions in opposing gradients of oxygen (O2) and dissolved Fe(II) (Fe2+). The goals of this study were to quantify the temporal development of O2 and Fe2+ concentrations over time, to compare abiotic and microbially inoculated tubes and to test the suitability of different Fe(II)-sources for the cultivation of freshwater and marine microaerophilic Fe(II)-oxidizers. O2 and Fe2+ gradients were monitored on a high spatial resolution as a function of time applying amperometric and voltammetric microsensors. Fe(II)-oxidizers could be cultivated well with FeS and zero-valent iron powder as Fe(II)-source, but FeCO3 and FeCl2 are extremely sensitive for this application. Fe(III) minerals accumulated in inoculated tubes within the first days in regions with an O2 concentration of 20-40 μM and were confirmed to be related to bacterial growth. Microbial Fe(II) oxidation could compete only for the first days with the abiotic reaction after which heterogeneous Fe(II) oxidation, catalyzed by Fe(III) minerals, dominated. Our results imply that transfer of cultures to fresh tubes within 48-72 h is crucial to provide optimal growth conditions for microaerophilic Fe(II)-oxidizers, particularly for the isolation of new strains.}, } @article {pmid29228184, year = {2018}, author = {Sansonetti, PJ}, title = {Editorial: Editorial for the virtual issue on microbiome.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {2}, pages = {113-115}, doi = {10.1093/femsre/fux058}, pmid = {29228184}, issn = {1574-6976}, mesh = {Animals ; Humans ; Microbiological Techniques/trends ; Microbiology/*trends ; *Microbiota ; }, } @article {pmid29228179, year = {2018}, author = {Signor, SA and New, FN and Nuzhdin, S}, title = {A Large Panel of Drosophila simulans Reveals an Abundance of Common Variants.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {189-206}, pmid = {29228179}, issn = {1759-6653}, support = {R01 GM102227/GM/NIGMS NIH HHS/United States ; R01 MH091561/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; Drosophila melanogaster/genetics ; Drosophila simulans/*genetics ; *Genetic Variation ; Genetics, Population ; Genomics ; Genotype ; Haplotypes ; Polymorphism, Genetic ; *Selection, Genetic ; Species Specificity ; }, abstract = {The rapidly expanding availability of large NGS data sets provides an opportunity to investigate population genetics at an unprecedented scale. Drosophila simulans is the sister species of the model organism Drosophila melanogaster, and is often presumed to share similar demographic history. However, previous population genetic and ecological work suggests very different signatures of selection and demography. Here, we sequence a new panel of 170 inbred genotypes of a North American population of D. simulans, a valuable complement to the DGRP and other D. melanogaster panels. We find some unexpected signatures of demography, in the form of excess intermediate frequency polymorphisms. Simulations suggest that this is possibly due to a recent population contraction and selection. We examine the outliers in the D. simulans genome determined by a haplotype test to attempt to parse the contribution of demography and selection to the patterns observed in this population. Untangling the relative contribution of demography and selection to genomic patterns of variation is challenging, however, it is clear that although D. melanogaster was thought to share demographic history with D. simulans different forces are at work in shaping genomic variation in this population of D. simulans.}, } @article {pmid29228173, year = {2018}, author = {Frost, HR and Sanderson-Smith, M and Walker, M and Botteaux, A and Smeesters, PR}, title = {Group A streptococcal M-like proteins: From pathogenesis to vaccine potential.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {2}, pages = {193-204}, doi = {10.1093/femsre/fux057}, pmid = {29228173}, issn = {1574-6976}, mesh = {Antigens, Bacterial/genetics/*immunology/metabolism ; Bacterial Outer Membrane Proteins/genetics/*immunology/metabolism ; Bacterial Proteins/genetics/*immunology/*metabolism ; Bacterial Vaccines/immunology ; Carrier Proteins/genetics/*immunology/metabolism ; Streptococcus/genetics/immunology/metabolism/pathogenicity ; Virulence Factors/metabolism ; }, abstract = {M and M-like surface proteins from group A Streptococcus (GAS) act as virulence factors and have been used in multiple vaccine candidates. While the M protein has been extensively studied, the two genetically and functionally related M-like proteins, Mrp and Enn, although present in most streptococcal strains have been relatively less characterised. We compile the current state of knowledge for these two proteins, from discovery to recent studies on function and immunogenicity, using the M protein for comparison as a prototype of this family of proteins. We focus on the known interactions between M-like proteins and host ligand proteins, and analyse the genetic data supporting these interactions. We discuss known and possible functions of M-like proteins during GAS infections, and highlight knowledge gaps where further investigation is warranted.}, } @article {pmid29228161, year = {2018}, author = {Gadkari, J and Goris, T and Schiffmann, CL and Rubick, R and Adrian, L and Schubert, T and Diekert, G}, title = {Reductive tetrachloroethene dehalogenation in the presence of oxygen by Sulfurospirillum multivorans: physiological studies and proteome analysis.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix176}, pmid = {29228161}, issn = {1574-6941}, abstract = {Reductive dehalogenation of organohalides is carried out by organohalide-respiring bacteria (OHRB) in anoxic environments. The tetrachloroethene (PCE)-respiring Epsilonproteobacterium Sulfurospirillum multivorans is one of few OHRB able to respire oxygen. Therefore, we investigated the organism's capacity to dehalogenate PCE in the presence of oxygen, which would broaden the applicability to use S. multivorans, unlike other commonly oxygen-sensitive OHRB, for bioremediation, e.g. at oxic/anoxic interphases. Additionally, this has an impact on our understanding of the global halogen cycle. Sulfurospirillum multivorans performs dehalogenation of PCE to cis-1,2-dichloroethene at oxygen concentrations below 0.19 mg/L. The redox potential of the medium electrochemically adjusted up to +400 mV had no influence on reductive dehalogenation by S. multivorans in our experiments, suggesting that higher levels of oxygen impair PCE dechlorination by inhibiting or inactivating involved enzymes. The PCE reductive dehalogenase remained active in cell extracts of S. multivorans exposed to 0.37 mg/L oxygen for more than 96 h. Analysis of the proteome revealed that superoxide reductase and cytochrome peroxidase amounts increased with 5% oxygen in the gas phase, while the response to atmospheric oxygen concentrations involved catalase and hydrogen peroxide reductase. Taken together, our results demonstrate that reductive dehalogenation by OHRB is not limited to anoxic conditions.}, } @article {pmid29227988, year = {2018}, author = {Pellegrini, AFA and Ahlström, A and Hobbie, SE and Reich, PB and Nieradzik, LP and Staver, AC and Scharenbroch, BC and Jumpponen, A and Anderegg, WRL and Randerson, JT and Jackson, RB}, title = {Fire frequency drives decadal changes in soil carbon and nitrogen and ecosystem productivity.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {194-198}, pmid = {29227988}, issn = {1476-4687}, mesh = {Calcium/analysis/metabolism ; Carbon/*analysis/deficiency/*metabolism ; Carbon Sequestration ; *Ecosystem ; Geographic Mapping ; Grassland ; Nitrogen/*analysis/deficiency/*metabolism ; Phosphorus/analysis/metabolism ; Potassium/analysis/metabolism ; Soil/*chemistry ; Spatio-Temporal Analysis ; Time Factors ; Wildfires/*statistics & numerical data ; }, abstract = {Fire frequency is changing globally and is projected to affect the global carbon cycle and climate. However, uncertainty about how ecosystems respond to decadal changes in fire frequency makes it difficult to predict the effects of altered fire regimes on the carbon cycle; for instance, we do not fully understand the long-term effects of fire on soil carbon and nutrient storage, or whether fire-driven nutrient losses limit plant productivity. Here we analyse data from 48 sites in savanna grasslands, broadleaf forests and needleleaf forests spanning up to 65 years, during which time the frequency of fires was altered at each site. We find that frequently burned plots experienced a decline in surface soil carbon and nitrogen that was non-saturating through time, having 36 per cent (±13 per cent) less carbon and 38 per cent (±16 per cent) less nitrogen after 64 years than plots that were protected from fire. Fire-driven carbon and nitrogen losses were substantial in savanna grasslands and broadleaf forests, but not in temperate and boreal needleleaf forests. We also observe comparable soil carbon and nitrogen losses in an independent field dataset and in dynamic model simulations of global vegetation. The model study predicts that the long-term losses of soil nitrogen that result from more frequent burning may in turn decrease the carbon that is sequestered by net primary productivity by about 20 per cent of the total carbon that is emitted from burning biomass over the same period. Furthermore, we estimate that the effects of changes in fire frequency on ecosystem carbon storage may be 30 per cent too low if they do not include multidecadal changes in soil carbon, especially in drier savanna grasslands. Future changes in fire frequency may shift ecosystem carbon storage by changing soil carbon pools and nitrogen limitations on plant growth, altering the carbon sink capacity of frequently burning savanna grasslands and broadleaf forests.}, } @article {pmid29227922, year = {2018}, author = {Gao, W and Howden, BP and Stinear, TP}, title = {Evolution of virulence in Enterococcus faecium, a hospital-adapted opportunistic pathogen.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {76-82}, doi = {10.1016/j.mib.2017.11.030}, pmid = {29227922}, issn = {1879-0364}, mesh = {Anti-Bacterial Agents/pharmacology ; Cross Infection/immunology/*microbiology ; Drug Resistance, Bacterial/genetics/immunology ; Enterococcus faecium/drug effects/*genetics/immunology/*pathogenicity ; *Evolution, Molecular ; Genome, Bacterial ; Gram-Positive Bacterial Infections/*microbiology ; Humans ; Microbial Sensitivity Tests ; Virulence ; Virulence Factors ; }, abstract = {Enterococci are long-standing members of the human microbiome and they are also widely distributed in nature. However, with the surge of antibiotic-resistance in recent decades, two enterococcal species (Enterococcus faecalis and Enterococcus faecium) have emerged to become significant nosocomial pathogens, acquiring extensive antibiotic resistance. In this review, we summarize what is known about the evolution of virulence in E. faecium, highlighting a specific clone of E. faecium called ST796 that has emerged recently and spread globally.}, } @article {pmid29227820, year = {2018}, author = {Dersch, S and Graumann, PL}, title = {The ultimate picture-the combination of live cell superresolution microscopy and single molecule tracking yields highest spatio-temporal resolution.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {55-61}, doi = {10.1016/j.mib.2017.11.027}, pmid = {29227820}, issn = {1879-0364}, mesh = {Bacteria/ultrastructure ; Cell Tracking/instrumentation/methods ; Cells/cytology/*ultrastructure ; Humans ; Microscopy, Fluorescence/instrumentation/*methods ; Proteins/ultrastructure ; Ribosomes/ultrastructure ; Single Molecule Imaging/*methods ; }, abstract = {We are witnessing a breathtaking development in light (fluorescence) microscopy, where structures can be resolved down to the size of a ribosome within cells. This has already yielded surprising insight into the subcellular structure of cells, including the smallest cells, bacteria. Moreover, it has become possible to visualize and track single fluorescent protein fusions in real time, and quantify molecule numbers within individual cells. Combined, super resolution and single molecule tracking are pushing the limits of our understanding of the spatio-temporal organization even of the smallest cells to an unprecedented depth.}, } @article {pmid29227220, year = {2018}, author = {Landwehr, W and Kämpfer, P and Glaeser, SP and Rückert, C and Kalinowski, J and Blom, J and Goesmann, A and Mack, M and Schumann, P and Atasayar, E and Hahnke, RL and Rohde, M and Martin, K and Stadler, M and Wink, J}, title = {Taxonomic analyses of members of the Streptomyces cinnabarinus cluster, description of Streptomyces cinnabarigriseus sp. nov. and Streptomyces davaonensis sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {382-393}, doi = {10.1099/ijsem.0.002519}, pmid = {29227220}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Philippines ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptomyces/*classification ; }, abstract = {Roseoflavin is the only known riboflavin (vitamin B2) analog with antibiotic properties. It is actively taken up by many micro-organisms and targets flavinmononucleotide riboswitches and flavoproteins. It is described as the product of the tentatively named 'Streptomyces davawensis' JCM 4913. Taxonomic analysis of this strain with a polyphasic approach showed that it is very closely related to Streptomyces cinnabarinus (DSM 40467). The two Streptomyces isolates were obtained from different geographical locations (the Philippines and the Kamchatka Peninsula, respectively), their genomes have been sequenced and the question was whether or not the two isolates were representatives of the same species. As we also worked with another isolate of Streptomyces cinnabarinus JS 360, the producer of the cinnabaramides, we wanted to clarify the taxonomic position of the three isolates by using a polyphasic approach. After analysis of the 16S rRNA gene sequence, we found in total 23 species of the genus Streptomyces that showed a similarity higher than 98.5 % to the three strains. We showed that 'S. davawensis' JCM 4913 and S. cinnabarinus DSM 40467 were very closely related but belong to two different species. Hence, we validate 'S. davawensis' as Streptomyces davaonensis sp. nov. with the type strain JCM 4913T (=DSM 101723T). In addition, the cinnabaramide producer can be clearly differentiated from S. davaonensis and this isolate is described as Streptomyces cinnabarigriseus sp. nov. with strain JS360T (=NCCB 100590T=DSM 101724T) as the type strain.}, } @article {pmid29227219, year = {2018}, author = {Gibtan, A and Song, HS and Kim, JY and Kim, YB and Park, N and Park, K and Lee, SJ and Kwon, J and Roh, SW and Lee, HS}, title = {Halorubrum aethiopicum sp. nov., an extremely halophilic archaeon isolated from commercial rock salt.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {416-422}, doi = {10.1099/ijsem.0.002525}, pmid = {29227219}, issn = {1466-5034}, mesh = {Base Composition ; DNA, Archaeal/genetics ; Ethiopia ; Halorubrum/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Sodium Chloride ; }, abstract = {A novel extremely halophilic archaeon, designated SAH-A6T, was isolated from a sample of commercial rock salt in Ethiopia. Cells of SAH-A6T were aerobic and pleomorphic. The strain was able to grow at concentrations of 15-30 % (w/v) NaCl (optimum 20-25 % NaCl), at pH 6.0-9.0 (optimum pH 7.0) and in a temperature range of 30-55 °C (optimum 37-45 °C). Mg2+ was not required for growth of SAH-A6T cells. On the basis of 16S rRNA gene sequence analysis, strain SAH-A6T was closely related to Halorubrum halodurans Cb34T (99.1 %), Halorubrum rubrum YC87T (98.9 %), Halorubrum aquaticum EN-2T (98.7 %), Halorubrum cibi JCM 15757T (98.4 %), Halorubrum luteum CGSA15T (97.3 %), Halorubrum lipolyticum 9-3T (97.1 %), Halorubrum tibetense 8W8T (97.1 %), Halorubrum kocurii JCM 1478T (97.1 %), Halorubrum halophilum B8T (97.0 %) and Halorubrum persicum C49T (97.0 %). Phylogenetic analysis based on the rpoB' gene sequences showed that strain SAH-A6T was closely related to Hrr. halodurans Cb34T (99.7 %), Hrr. aquaticum JCM 14031T (99.3 %) and other members of the genus Halorubrum (<99.0 %). The DNA G+C content of the strain was 68.0 mol%. DNA-DNA hybridization between strain SAH-A6T and the most closely related members of the genus Halorubrum were below 55 %, suggesting that the new isolate constitutes a different genospecies. On the bases of chemotaxonomic, phenotypic and genotypic data, strain SAH-A6T (=KCCM 43215T=JCM 31519T) represents a novel species of the genus Halorubrum, for which the name Halorubrumaethiopicum sp. nov. is proposed.}, } @article {pmid29225357, year = {2018}, author = {Hofer, U}, title = {Marine microbiology: Illuminating the importance of nitrite oxidation.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {64-65}, pmid = {29225357}, issn = {1740-1534}, } @article {pmid29225335, year = {2018}, author = {Timpson, NJ and Greenwood, CMT and Soranzo, N and Lawson, DJ and Richards, JB}, title = {Genetic architecture: the shape of the genetic contribution to human traits and disease.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {110-124}, pmid = {29225335}, issn = {1471-0064}, support = {G9815508//Medical Research Council/United Kingdom ; MC_PC_15018//Medical Research Council/United Kingdom ; MC_UU_12013/3//Medical Research Council/United Kingdom ; }, abstract = {Genetic architecture describes the characteristics of genetic variation that are responsible for heritable phenotypic variability. It depends on the number of genetic variants affecting a trait, their frequencies in the population, the magnitude of their effects and their interactions with each other and the environment. Defining the genetic architecture of a complex trait or disease is central to the scientific and clinical goals of human genetics, which are to understand disease aetiology and aid in disease screening, diagnosis, prognosis and therapy. Recent technological advances have enabled genome-wide association studies and emerging next-generation sequencing studies to begin to decipher the nature of the heritable contribution to traits and disease. Here, we describe the types of genetic architecture that have been observed, how architecture can be measured and why an improved understanding of genetic architecture is central to future advances in the field.}, } @article {pmid29225334, year = {2018}, author = {Kaniecki, K and De Tullio, L and Greene, EC}, title = {A change of view: homologous recombination at single-molecule resolution.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {4}, pages = {191-207}, pmid = {29225334}, issn = {1471-0064}, support = {R35 GM118026/GM/NIGMS NIH HHS/United States ; }, abstract = {Genetic recombination occurs in all organisms and is vital for genome stability. Indeed, in humans, aberrant recombination can lead to diseases such as cancer. Our understanding of homologous recombination is built upon more than a century of scientific inquiry, but achieving a more complete picture using ensemble biochemical and genetic approaches is hampered by population heterogeneity and transient recombination intermediates. Recent advances in single-molecule and super-resolution microscopy methods help to overcome these limitations and have led to new and refined insights into recombination mechanisms, including a detailed understanding of DNA helicase function and synaptonemal complex structure. The ability to view cellular processes at single-molecule resolution promises to transform our understanding of recombination and related processes.}, } @article {pmid29225333, year = {2018}, author = {Lieben, L}, title = {Technique: A miniature living recording device.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {65}, pmid = {29225333}, issn = {1471-0064}, } @article {pmid29224891, year = {2018}, author = {Soukup, V and Kozmik, Z}, title = {The Bmp signaling pathway regulates development of left-right asymmetry in amphioxus.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {164-174}, doi = {10.1016/j.ydbio.2017.12.004}, pmid = {29224891}, issn = {1095-564X}, mesh = {Animals ; Bone Morphogenetic Proteins/*metabolism ; Embryo, Nonmammalian/cytology/*embryology ; Gene Expression Regulation, Developmental/*physiology ; Lancelets/cytology/*embryology ; Left-Right Determination Factors/biosynthesis ; Nodal Protein/metabolism ; Signal Transduction/*physiology ; }, abstract = {Establishment of asymmetry along the left-right (LR) body axis in vertebrates requires interplay between Nodal and Bmp signaling pathways. In the basal chordate amphioxus, the left-sided activity of the Nodal signaling has been attributed to the asymmetric morphogenesis of paraxial structures and pharyngeal organs, however the role of Bmp signaling in LR asymmetry establishment has not been addressed to date. Here, we show that Bmp signaling is necessary for the development of LR asymmetric morphogenesis of amphioxus larvae through regulation of Nodal signaling. Loss of Bmp signaling results in loss of the left-sided expression of Nodal, Gdf1/3, Lefty and Pitx and in gain of ectopic expression of Cerberus on the left side. As a consequence, the larvae display loss of the offset arrangement of axial structures, loss of the left-sided pharyngeal organs including the mouth, and ectopic development of the right-sided organs on the left side. Bmp inhibition thus phenocopies inhibition of Nodal signaling and results in the right isomerism. We conclude that Bmp and Nodal pathways act in concert to specify the left side and that Bmp signaling plays a fundamental role during LR development in amphioxus.}, } @article {pmid29224786, year = {2018}, author = {Drovetski, SV and Reeves, AB and Red'kin, YA and Fadeev, IV and Koblik, EA and Sotnikov, VN and Voelker, G}, title = {Multi-locus reassessment of a striking discord between mtDNA gene trees and taxonomy across two congeneric species complexes.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {43-52}, doi = {10.1016/j.ympev.2017.11.023}, pmid = {29224786}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Cell Nucleus/genetics ; DNA, Mitochondrial/*genetics ; *Genetic Loci ; Geography ; Haplotypes/genetics ; Introns/genetics ; NADH Dehydrogenase/genetics ; Passeriformes/*genetics ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Resolving relationships among members of the yellow and citrine wagtail species complexes is among the greatest challenges in avian systematics due to arguably the most dramatic disagreements between traditional taxonomy and mtDNA phylogeny. Each species complex is divided into three geographically cohesive mtDNA clades. Each clade from one species complex has a sister from the other complex. Furthermore, one cross-complex pair is more distantly related to the remaining two pairs than are several other wagtail species. To test mtDNA gene tree topology, we sequenced the mtDNA ND2 gene and 11 nuclear introns for seven wagtail species. Our mtDNA gene tree reconstruction supported the results of previous studies, thereby confirming the disagreement between mtDNA phylogeny and taxonomy. However, our multi-locus species tree which used mtDNA clades as "taxa" was consistent with traditional taxonomy regardless of whether mtDNA was included in the analysis or not. Our multi-locus data suggest that despite the presence of strongly supported, geographically structured mtDNA variation, the mtDNA gene tree misrepresents the evolutionary history of the yellow and citrine wagtail complexes. This mito-nuclear discord results from mtDNA representing the biogeographic, but not evolutionary history of these recently radiated Palearctic wagtails.}, } @article {pmid29224785, year = {2018}, author = {San Jose, M and Doorenweerd, C and Leblanc, L and Barr, N and Geib, S and Rubinoff, D}, title = {Incongruence between molecules and morphology: A seven-gene phylogeny of Dacini fruit flies paves the way for reclassification (Diptera: Tephritidae).}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {139-149}, doi = {10.1016/j.ympev.2017.12.001}, pmid = {29224785}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Bayes Theorem ; DNA, Mitochondrial/genetics ; *Genes, Insect ; Geography ; *Phylogeny ; Tephritidae/*classification/*genetics ; }, abstract = {Molecular and morphological research often suggest conflicting results. Selective pressure on certain morphologies can confound understanding of evolutionary relationships. Dacini is one of the most diverse tribes of tephritid flies and contains many economically important pest species. Their black and yellow patterned body markings are presumed to act as wasp mimicry, and the characters separating species and groups are limited and in some cases phenotypically plastic. The traditional taxonomy of the tribe is controversial because groupings are based on unique combinations of morphological characters without the use of cladistic methods, though recent phylogenetic and taxonomic analyses have resulted in significant changes to their taxonomy. The monophyly of the three largest genera in the tribe has been tested with only small numbers of representatives per genus and a limited number of genes. To further understand the taxonomy and evolution of Dacini we sequenced seven genes from 167 Dacini species and five dipteran outgroups to construct a robust phylogeny and test phylogenetic relationships between genera, subgenera, and species complexes. Our phylogeny confirms the monophyly of Dacus, Bactrocera, and Zeugodacus. However, most groups below the genus level are not monophyletic, and only through further revision will we be able to understand their evolution and clarify the taxonomy within this tribe.}, } @article {pmid29224051, year = {2018}, author = {Alugoju, P and Janardhanshetty, SS and Subaramanian, S and Periyasamy, L and Dyavaiah, M}, title = {Quercetin Protects Yeast Saccharomyces cerevisiae pep4 Mutant from Oxidative and Apoptotic Stress and Extends Chronological Lifespan.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {519-530}, pmid = {29224051}, issn = {1432-0991}, support = {(F NO 42-665/2013 (SR dated 25-03-2013))//UGC-BSR/ ; }, mesh = {Acetic Acid/pharmacology ; Apoptosis/*drug effects ; Aspartic Acid Endopeptidases/genetics/*metabolism ; Hydrogen Peroxide/pharmacology ; Oxidative Stress/*drug effects ; Quercetin/*pharmacology ; Reactive Oxygen Species/metabolism ; Saccharomyces cerevisiae/*drug effects/*enzymology/genetics/metabolism ; Saccharomyces cerevisiae Proteins/genetics/*metabolism ; }, abstract = {The yeast Saccharomyces cerevisiae PEP4 gene encodes vacuolar endopeptidase proteinase A (Pep4p), which is a homolog of the human CTSD gene that encodes cathepsin D. Mutation of CTSD gene in human resulted in a number of neurodegenerative diseases. In this study, we have shown that yeast pep4 mutant cells are highly sensitive to oxidative and apoptotic stress induced by hydrogen peroxide and acetic acid, respectively. pep4∆ cells also showed accumulation of reactive oxygen species (ROS), apoptotic markers, and reduced chronological lifespan. In contrast, quercetin pretreatment protected the pep4 mutant from oxidative and apoptotic stress-induced sensitivity by scavenging ROS and reducing apoptotic markers. The percentage viability of quercetin-treated pep4∆ cells was more pronounced and increased stress resistance against oxidant, apoptotic, and heat stress during chronological aging. From our experimental results, we concluded that quercetin protects yeast pep4 mutant cells from oxidative stress and apoptosis, thereby increasing viability during chronological aging.}, } @article {pmid29223862, year = {2018}, author = {Sasidharan, S and Borinskaya, S and Patel, F and Bernadskaya, Y and Mandalapu, S and Agapito, M and Soto, MC}, title = {WAVE regulates Cadherin junction assembly and turnover during epithelial polarization.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {133-148}, pmid = {29223862}, issn = {1095-564X}, support = {K12 GM093854/GM/NIGMS NIH HHS/United States ; R01 GM081670/GM/NIGMS NIH HHS/United States ; S10 OD010572/OD/NIH HHS/United States ; }, mesh = {Animals ; Cadherins/genetics/*metabolism ; Caenorhabditis elegans/*embryology/genetics/ultrastructure ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Polarity/*physiology ; Embryo, Nonmammalian/cytology/*embryology/ultrastructure ; Epithelial Cells/*metabolism/ultrastructure ; Tight Junctions/genetics/*metabolism/ultrastructure ; }, abstract = {Actin is an integral component of epithelial apical junctions, yet the interactions of branched actin regulators with apical junction components are still not clear. Biochemical data have shown that α-catenin inhibits Arp2/3-dependent branched actin. These results suggested that branched actin is only needed at earliest stages of apical junction development. We use live imaging in developing C. elegans embryos to test models for how WAVE-induced branched actin collaborates with other apical junction proteins during the essential process of junction formation and maturation. We uncover both early and late essential roles for WAVE in apical junction formation. Early, as the C. elegans intestinal epithelium becomes polarized, we find that WAVE components become enriched concurrently with the Cadherin components and before the DLG-1 apical accumulation. Live imaging of F-actin accumulation in polarizing intestine supports that the Cadherin complex components and branched actin regulators work together for apical actin enrichment. Later in junction development, the apical accumulation of WAVE and Cadherin components is shown to be interdependent: Cadherin complex loss alters WAVE accumulation, and WAVE complex loss increases Cadherin accumulation. To determine why Cadherin levels rise when WVE-1 is depleted, we use FRAP to analyze Cadherin dynamics and find that loss of WAVE as well as of the trafficking protein EHD-1/RME-1 increases Cadherin dynamics. EM studies in adults depleted of branched actin regulators support that WVE-1 maintains established junctions, presumably through its trafficking effect on Cadherin. Thus we propose a developmental model for junction formation where branched actin regulators are tightly interconnected with Cadherin junctions through their previously unappreciated role in Cadherin transport.}, } @article {pmid29223292, year = {2018}, author = {Niskanen, M and Junno, JA and Maijanen, H and Holt, B and Sladék, V and Berner, M}, title = {Can we refine body mass estimations based on femoral head breadth?.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {112-121}, doi = {10.1016/j.jhevol.2017.10.015}, pmid = {29223292}, issn = {1095-8606}, abstract = {Femoral head breadth is widely used in body mass estimation in biological anthropology. Earlier research has demonstrated that reduced major axis (RMA) equations perform better than least squares (LS) equations. Although a simple RMA equation to estimate body size from femoral head breadth is sufficient in most cases, our experiments with male skeletons from European data (including late Pleistocene and Holocene skeletal samples) and the Forensic Anthropology Data Bank data (including the W. M. Bass Donated Skeletal Collection sample) show that including femoral length or anatomically estimated stature in an equation with femoral head breadth improves body mass estimation precision. More specifically, although directional bias related to body mass is not reduced within specific samples, the total estimation error range, directional bias related to stature, and temporal fluctuation in estimation error are markedly reduced. The overall body mass estimation precision of individuals representing different temporal periods and ancestry groups (e.g., African and European ancestry) is thus improved.}, } @article {pmid29222621, year = {2018}, author = {Kwon, G and Lee, J and Koh, JH and Lim, YH}, title = {Lifespan Extension of Caenorhabditis elegans by Butyricicoccus pullicaecorum and Megasphaera elsdenii with Probiotic Potential.}, journal = {Current microbiology}, volume = {75}, number = {5}, pages = {557-564}, pmid = {29222621}, issn = {1432-0991}, support = {K1711191//Korea University Grant/ ; }, mesh = {Animals ; Caenorhabditis elegans/drug effects/genetics/*growth & development/*microbiology ; Caenorhabditis elegans Proteins/genetics/metabolism ; Clostridiales/*physiology ; Megasphaera elsdenii/*physiology ; Probiotics/*pharmacology ; }, abstract = {Butyricicoccus pullicaecorum and Megasphaera elsdenii inhabit the human intestine and have probiotic potential. The aim of this study was to evaluate the effects of B. pullicaecorum and M. elsdenii on the lifespan of Caenorhabditis elegans. They significantly (P < 0.05) extended the lifespan of C. elegans compared with Escherichia coli OP50, a standard food for the worm. Analysis of age-related biomarkers such as lipofuscin, body size, and locomotory activity showed that they retarded aging. They all failed to extend the lifespan of daf-12 or dbl-1 loss-of-function C. elegans mutants compared with E. coli OP50-fed worms. However, the increase in lifespan was observed in daf-16, jnk-1, pmk-1, and skn-1 mutants. Moreover, they increased the resistance of C. elegans to a human pathogen, Salmonella typhimurium. In conclusion, B. pullicaecorum and M. elsdenii extend the lifespan of C. elegans via the transforming growth factor-beta (TGF-β) pathway associated with anti-inflammatory processes in the innate immune system.}, } @article {pmid29222065, year = {2018}, author = {Devecchi, MF and Thomas, WW and Plunkett, GM and Pirani, JR}, title = {Testing the monophyly of Simaba (Simaroubaceae): Evidence from five molecular regions and morphology.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {63-82}, doi = {10.1016/j.ympev.2017.11.024}, pmid = {29222065}, issn = {1095-9513}, mesh = {Base Sequence ; Bayes Theorem ; Cell Nucleus/genetics ; Consensus Sequence ; DNA, Plant/genetics ; Geography ; Introns/genetics ; *Phylogeny ; Sequence Analysis, DNA ; Simaroubaceae/anatomy & histology/*classification/*genetics/ultrastructure ; Species Specificity ; }, abstract = {Generic circumscriptions in the mostly pantropical family Simaroubaceae are somewhat controversial. Simaba is the largest genus, currently defined as exclusively neotropical, with around 25 species of trees and shrubs, but both its limits and infrageneric classification have been a matter of discussion and divergence. Traditionally, species of the genus have been treated in three sections: Simaba sect. Tenuiflorae, S. sect. Floribundae and S. sect. Grandiflorae, but a phylogenetic analysis suggested that the latter two may not be monophyletic. To test the monophyly of Simaba and its infrageneric classification, we used a molecular approach based on DNA sequence data from two nuclear ribosomal spacer regions (ITS and ETS) and three plastid regions (rps16 intron, and intergenic spacers psbA-trnH and trnL-trnF), including a comprehensive sampling of species from Simaba and closely related genera. We also performed ancestral character reconstructions to identify morphological characters that could serve as synapomorphies for major clades and to explore patterns of homoplasy in the morphological dataset. Our results show Simaba as traditionally circumscribed is not monophyletic, with taxa segregated into two strongly supported but distinct clades, one of which is more closely related to Simarouba. The three main clades that emerged in the phylogeny include a mostly Amazonian Simaba clade (which includes the type species of Simaba and the remaining species of S. sect. Tenuiflorae, here proposed to be recognized as Simaba sensu stricto), a mostly extra-Amazonian Simaba clade (a distinct lineage that will be recognized as Homalolepis, a genus currently treated in synonymy and equivalent to Simaba sections Grandiflorae and Floribundae), and the Simarouba clade (including all of its current species). These three clades are characterized by a combination of morphological characters, described in detail herein, some of which are novel features for Simaba not previously reported in the literature. Mapping character-states on the phylogenetic tree provides tests for evolutionary hypotheses. For example, our reconstruction of habit and geographic distribution suggests that the diversification of several shrubby species within the extra-Amazonian lineage in the South American cerrados probably occurred from ancestors inhabiting tropical forests, involving transitions in morphological and ecological traits.}, } @article {pmid29222064, year = {2018}, author = {Tosso, F and Hardy, OJ and Doucet, JL and Daïnou, K and Kaymak, E and Migliore, J}, title = {Evolution in the Amphi-Atlantic tropical genus Guibourtia (Fabaceae, Detarioideae), combining NGS phylogeny and morphology.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {83-93}, doi = {10.1016/j.ympev.2017.11.026}, pmid = {29222064}, issn = {1095-9513}, mesh = {Africa ; Atlantic Ocean ; Evolution, Molecular ; Fabaceae/*anatomy & histology/*classification ; Geography ; Likelihood Functions ; *Phylogeny ; Plastids/genetics ; Principal Component Analysis ; Rainforest ; Sequence Analysis, DNA ; Species Specificity ; Time Factors ; *Tropical Climate ; }, abstract = {Tropical rain forests support a remarkable diversity of tree species, questioning how and when this diversity arose. The genus Guibourtia (Fabaceae, Detarioideae), characterized by two South American and 13 African tree species growing in various tropical biomes, is an interesting model to address the role of biogeographic processes and adaptation to contrasted environments on species diversification. Combining whole plastid genome sequencing and morphological characters analysis, we studied the timing of speciation and diversification processes in Guibourtia through molecular dating and ancestral habitats reconstruction. All species except G. demeusei and G. copallifera appear monophyletic. Dispersal from Africa to America across the Atlantic Ocean is the most plausible hypothesis to explain the occurrence of Neotropical Guibourtia species, which diverged ca. 11.8 Ma from their closest African relatives. The diversification of the three main clades of African Guibourtia is concomitant to Miocene global climate changes, highlighting pre-Quaternary speciation events. These clades differ by their reproductive characters, which validates the three subgenera previously described: Pseudocopaiva, Guibourtia and Gorskia. Within most monophyletic species, plastid lineages start diverging from each other during the Pliocene or early Pleistocene, suggesting that these species already arose during this period. The multiple transitions between rain forests and dry forests/savannahs inferred here through the plastid phylogeny in each Guibourtia subgenus address thus new questions about the role of phylogenetic relationships in shaping ecological niche and morphological similarity among taxa.}, } @article {pmid29222063, year = {2018}, author = {Medina, R and Johnson, M and Liu, Y and Wilding, N and Hedderson, TA and Wickett, N and Goffinet, B}, title = {Evolutionary dynamism in bryophytes: Phylogenomic inferences confirm rapid radiation in the moss family Funariaceae.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {240-247}, doi = {10.1016/j.ympev.2017.12.002}, pmid = {29222063}, issn = {1095-9513}, mesh = {Bryophyta/*classification/genetics ; Bryopsida/genetics ; DNA, Plant/chemistry/genetics/metabolism ; *Evolution, Molecular ; Exons ; High-Throughput Nucleotide Sequencing ; Phylogeny ; Plastids/classification/genetics ; Sequence Analysis, DNA ; }, abstract = {Rapid diversifications of plants are primarily documented and studied in angiosperms, which are perceived as evolutionarily dynamic. Recent studies have, however, revealed that bryophytes have also undergone periods of rapid radiation. The speciose family Funariaceae, including the model taxon Physcomitrella patens, is one such lineage. Here, we infer relationships among major lineages within the Entosthodon-Physcomitrium complex from virtually complete organellar exomes (i.e., 123 genes) obtained through high throughput sequencing of genomic libraries enriched in these loci via targeted locus capture. Based on these extensive exonic data we (1) reconstructed a robust backbone topology of the Funariaceae, (2) confirmed the monophyly of Funaria and the polyphyly of Entosthodon, Physcomitrella, and Physcomitrium, and (3) argue for the occurrence of a rapid radiation within the Entosthodon-Physcomitrium complex that began 28 mya and gave rise more than half of the species diversity of the family. This diversification may have been triggered by a whole genome duplication and coincides with global Eocene cooling that continued through the Oligocene and Miocene. The Funariaceae join a growing list of bryophyte lineages whose history is marked by at least one burst of diversification, and our study thereby strengthens the view that bryophytes are evolutionarily dynamic lineages and that patterns and processes characterizing the evolution of angiosperms may be universal among land plants.}, } @article {pmid29222062, year = {2018}, author = {Rody, HVS and Oliveira, LO}, title = {Evolutionary history of the cobalamin-independent methionine synthase gene family across the land plants.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {33-42}, doi = {10.1016/j.ympev.2017.12.003}, pmid = {29222062}, issn = {1095-9513}, mesh = {Bayes Theorem ; Embryophyta/*enzymology/*genetics ; *Evolution, Molecular ; Gene Duplication ; Gene Expression Profiling ; Genes, Duplicate ; *Genes, Plant ; Genotype ; Methyltransferases/*genetics ; *Multigene Family ; Phylogeny ; Sequence Homology, Nucleic Acid ; Soybeans/enzymology/genetics ; }, abstract = {Plants are successful paleopolyploids. The wide diversity of land plants is driven strongly by their gene duplicates undergoing distinct evolutionary fates after duplication. We used genomic resources from 35 model plant species to unravel the evolutionary fate of gene copies (paralogs) of the cobalamin-independent methionine synthase (metE) gene family across the land plants. To explore genealogical relationships and characterize positive selection as a driving force in the evolution of metE paralogs within a single species, we carried out complementary analyses on genomic data of 32 genotypes of soybean. The size of the metE gene family remained small across the land plants; most of the studied species possessed 1-6 paralogs. Gene products were either cytosolic or chloroplastic; this dual subcellular distribution arose early during the divergence of the land plants and reached all extant lineages. Biased gene loss and gene retention events took place multiple times; recurrent evolution remodeled redundant metE paralogs to recover and maintain the dual subcellular distribution of MetE. Shared whole-genome duplication events gave rise to the metE paralogs of both soybean and Medicago truncatula. In soybean, the ancestral paralog pair GlymaPP2A encoded a cytosolic isoform of MetE, was under strong purifying selection, and retained high levels of expression across eight RNA-seq expression libraries. The daughters GlymaPP1 and GlymaPP2B showed accelerated rates of evolution, accumulated many sites predicted to be under positive selection, and possessed low levels of expression. Our results suggest that the metE paralogs of soybean follow Ohno's neofunctionalization model of gene duplicate evolution.}, } @article {pmid29221677, year = {2018}, author = {Stevenson, TJ}, title = {Epigenetic Regulation of Biological Rhythms: An Evolutionary Ancient Molecular Timer.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {90-100}, doi = {10.1016/j.tig.2017.11.003}, pmid = {29221677}, issn = {0168-9525}, mesh = {Animals ; Bacteria/genetics/metabolism ; DNA Methylation ; Dinoflagellida/genetics/metabolism ; *Epigenesis, Genetic ; Histones/*genetics/metabolism ; Humans ; *Models, Genetic ; *Periodicity ; Photoperiod ; Plants/genetics/metabolism ; Saccharomyces cerevisiae/genetics/metabolism ; Transcription, Genetic ; }, abstract = {Biological rhythms are pervasive in nature, yet our understanding of the molecular mechanisms that govern timing is far from complete. The rapidly emerging research focus on epigenetic plasticity has revealed a system that is highly dynamic and reversible. In this Opinion, I propose an epigenetic clock model that outlines how molecular modifications, such as DNA methylation, are integral components for timing endogenous biological rhythms. The hypothesis proposed is that an epigenetic clock serves to maintain the period of molecular rhythms via control over the phase of gene transcription and this timing mechanism resides in all cells, from unicellular to complex organisms. The model also provides a novel framework for the timing of epigenetic modifications during the lifespan and transgenerational inheritance of an organism.}, } @article {pmid29220874, year = {2018}, author = {Fox, CW and Messina, FJ}, title = {Evolution of larval competitiveness and associated life-history traits in response to host shifts in a seed beetle.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {302-313}, doi = {10.1111/jeb.13222}, pmid = {29220874}, issn = {1420-9101}, abstract = {Resource competition is frequently strong among parasites that feed within small discrete resource patches, such as seeds or fruits. The properties of a host can influence the behavioural, morphological and life-history traits of associated parasites, including traits that mediate competition within the host. For seed parasites, host size may be an especially important determinant of competitive ability. Using the seed beetle, Callosobruchus maculatus, we performed replicated, reciprocal host shifts to examine the role of seed size in determining larval competitiveness and associated traits. Populations ancestrally associated with either a small host (mung bean) or a large one (cowpea) were switched to each other's host for 36 generations. Compared to control lines (those remaining on the ancestral host), lines switched from the small host to the large host evolved greater tolerance of co-occurring larvae within seeds (indicated by an increase in the frequency of small seeds yielding two adults), smaller egg size and higher fecundity. Each change occurred in the direction predicted by the traits of populations already adapted to cowpea. However, we did not observe the expected decline in adult mass following the shift to the larger host. Moreover, lines switched from the large host (cowpea) to the small host (mung bean) did not evolve the predicted increase in larval competitiveness or egg size, but did exhibit the predicted increase in body mass. Our results thus provide mixed support for the hypothesis that host size determines the evolution of competition-related traits of seed beetles. Evolutionary responses to the two host shifts were consistent among replicate lines, but the evolution of larval competition was asymmetric, with larval competitiveness evolving as predicted in one direction of host shift, but not the reverse. Nevertheless, our results indicate that switching hosts is sufficient to produce repeatable and rapid changes in the competition strategy and fitness-related traits of insect populations.}, } @article {pmid29220506, year = {2018}, author = {Vakirlis, N and Hebert, AS and Opulente, DA and Achaz, G and Hittinger, CT and Fischer, G and Coon, JJ and Lafontaine, I}, title = {A Molecular Portrait of De Novo Genes in Yeasts.}, journal = {Molecular biology and evolution}, volume = {35}, number = {3}, pages = {631-645}, pmid = {29220506}, issn = {1537-1719}, support = {P41 GM108538/GM/NIGMS NIH HHS/United States ; }, abstract = {New genes, with novel protein functions, can evolve "from scratch" out of intergenic sequences. These de novo genes can integrate the cell's genetic network and drive important phenotypic innovations. Therefore, identifying de novo genes and understanding how the transition from noncoding to coding occurs are key problems in evolutionary biology. However, identifying de novo genes is a difficult task, hampered by the presence of remote homologs, fast evolving sequences and erroneously annotated protein coding genes. To overcome these limitations, we developed a procedure that handles the usual pitfalls in de novo gene identification and predicted the emergence of 703 de novo gene candidates in 15 yeast species from 2 genera whose phylogeny spans at least 100 million years of evolution. We validated 85 candidates by proteomic data, providing new translation evidence for 25 of them through mass spectrometry experiments. We also unambiguously identified the mutations that enabled the transition from noncoding to coding for 30 Saccharomyces de novo genes. We established that de novo gene origination is a widespread phenomenon in yeasts, only a few being ultimately maintained by selection. We also found that de novo genes preferentially emerge next to divergent promoters in GC-rich intergenic regions where the probability of finding a fortuitous and transcribed ORF is the highest. Finally, we found a more than 3-fold enrichment of de novo genes at recombination hot spots, which are GC-rich and nucleosome-free regions, suggesting that meiotic recombination contributes to de novo gene emergence in yeasts.}, } @article {pmid29220501, year = {2018}, author = {Voskarides, K}, title = {Combination of 247 Genome-Wide Association Studies Reveals High Cancer Risk as a Result of Evolutionary Adaptation.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {473-485}, pmid = {29220501}, issn = {1537-1719}, abstract = {Analysis of GLOBOCAN-2012 data shows clearly here that cancer incidence worldwide is highly related with low average annual temperatures and extreme low temperatures. This applies for all cancers together or separately for many frequent or rare cancer types (all cancers P = 9.49×10-18). Supporting fact is that Inuit people, living at extreme low temperatures, have the highest cancer rates today. Hypothesizing an evolutionary explanation, 240 cancer genome-wide association studies, and seven genome-wide association studies for cold and high-altitude adaptation were combined. A list of 1,377 cancer-associated genes was created to initially investigate whether cold selected genes are enriched with cancer-associated genes. Among Native Americans, Inuit and Eskimos, the highest association was observed for Native Americans (P = 6.7×10-5). An overall or a meta-analysis approach confirmed further this result. Similar approach for three populations living at extreme high altitude, revealed high association for Andeans-Tibetans (P = 1.3×10-11). Overall analysis or a meta-analysis was also significant. A separate analysis showed special selection for tumor suppressor genes. These results can be viewed along with those of previous functional studies that showed that reduced apoptosis potential due to specific p53 variants (the most important tumor suppressor gene) is beneficial in high-altitude and cold environments. In conclusion, this study shows that genetic variants selected for adaptation at extreme environmental conditions can increase cancer risk later on age. This is in accordance with antagonistic pleiotropy hypothesis.}, } @article {pmid29220490, year = {2018}, author = {Zhang, C and Ogilvie, HA and Drummond, AJ and Stadler, T}, title = {Bayesian Inference of Species Networks from Multilocus Sequence Data.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {504-517}, pmid = {29220490}, issn = {1537-1719}, abstract = {Reticulate species evolution, such as hybridization or introgression, is relatively common in nature. In the presence of reticulation, species relationships can be captured by a rooted phylogenetic network, and orthologous gene evolution can be modeled as bifurcating gene trees embedded in the species network. We present a Bayesian approach to jointly infer species networks and gene trees from multilocus sequence data. A novel birth-hybridization process is used as the prior for the species network, and we assume a multispecies network coalescent prior for the embedded gene trees. We verify the ability of our method to correctly sample from the posterior distribution, and thus to infer a species network, through simulations. To quantify the power of our method, we reanalyze two large data sets of genes from spruces and yeasts. For the three closely related spruces, we verify the previously suggested homoploid hybridization event in this clade; for the yeast data, we find extensive hybridization events. Our method is available within the BEAST 2 add-on SpeciesNetwork, and thus provides an extensible framework for Bayesian inference of reticulate evolution.}, } @article {pmid29220418, year = {2018}, author = {Kumaran, N and van der Burg, CA and Qin, Y and Cameron, SL and Clarke, AR and Prentis, PJ}, title = {Plant-Mediated Female Transcriptomic Changes Post-Mating in a Tephritid Fruit Fly, Bactrocera tryoni.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {94-107}, pmid = {29220418}, issn = {1759-6653}, mesh = {Animals ; Female ; Fertility ; Gene Ontology ; Herbivory ; Male ; Plants/metabolism ; Reproduction ; *Sexual Behavior, Animal ; Tephritidae/*genetics/physiology ; *Transcriptome ; }, abstract = {Female post-mating behaviors are regulated by complex factors involving males, females, and the environment. In insects, plant secondary compounds that males actively forage for, may indirectly modify female behaviors by altering male behavior and physiology. In the tephritid fruit fly, Bactrocera tryoni, females mated with males previously fed on plant-derived phenylpropanoids (="lures" based on usage in tephritid literature), have longer mating refractoriness, greater fecundity, and reduced longevity than females mated with non-lure fed males. This system thus provides a model for studying transcriptional changes associated with those post-mating behaviors, as the genes regulating the phenotypic changes are likely to be expressed at a greater magnitude than in control females. We performed comparative transcriptome analyses using virgin B. tryoni females, females mated with control males (control-mated), and females mated with lure-fed males (lure-mated). We found 331 differentially expressed genes (DEGs) in control-mated females and 80 additional DEGs in lure-mated females. Although DEGs in control-mated females are mostly immune response genes and chorion proteins, as reported in Drosophila species, DEGs in lure-mated females are titin-like muscle proteins, histones, sperm, and testis expressed proteins which have not been previously reported. While transcripts regulating mating (e.g., lingerer) did not show differential expression in either of the mated female classes, the odorant binding protein Obp56a was down-regulated. The exclusively enriched or suppressed genes in lure-mated females, novel transcripts such as titin and histones, and several taxa-specific transcripts reported here can shed more light on post-mating transcriptional changes, and this can help understand factors possibly regulating female post-mating behaviors.}, } @article {pmid29219808, year = {2018}, author = {Dahal, RH and Kim, J}, title = {Ferrovibrio soli sp. nov., a novel cellulolytic bacterium isolated from stream bank soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {427-431}, doi = {10.1099/ijsem.0.002527}, pmid = {29219808}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodospirillaceae/*classification/genetics/isolation & purification ; *Rivers ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {Two isolates of bacterial strains A15T and A17 were isolated from stream bank soil in Kyonggi University. Cells were aerobic, Gram-stain-negative, oxidase- and catalase-positive, motile, non-spore-forming, rod-shaped, opaque, and cream coloured. Both strains hydrolysed CM-cellulose. Strains were able to grow at 20-42 °C, pH 5.5-10.0 and at 1.5 % NaCl concentration (w/v). Indole test was positive. Analyses of phylogenetic trees based on its 16S rRNA gene sequences indicated that strain A15T formed a lineage within the family Rhodospirillaceae of the phylum Proteobacteria which was distinct from Ferrovibrio denitrificans S3T (98.4 % sequence similarity) and Ferrovibrio xuzhouensis LM-6T (97.4 %). The sole detected respiratory quinone was Q-10. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and an unidentified aminolipid. The major cellular fatty acids were C19 : 0 cycloω8c, C16 : 0, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C18 : 0cyclo and C12 : 0. The DNA G+C contents of strains A15T and A17 were 63.4 and 62.9 mol%, respectively. DNA-DNA relatedness between strain A15T and other two members of the genus Ferrovibrioranged from 25 to 37 %. The polyphasic characterization revealed strains A15T and A17 represent a novel species in the genus Ferrovibrio, for which the name Ferrovibriosoli sp. nov. is proposed. The type strain is A15T (=KEMB 9005-522T=KACC 19102T=NBRC 112682T).}, } @article {pmid29219806, year = {2018}, author = {Chen, WM and Hsieh, TY and Sheu, SY}, title = {Mucilaginibacter amnicola sp. nov., isolated from a freshwater creek.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {394-401}, doi = {10.1099/ijsem.0.002518}, pmid = {29219806}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hydroxybutyrates/metabolism ; Phospholipids/chemistry ; *Phylogeny ; Polyesters/metabolism ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; Spermidine/chemistry ; Taiwan ; Vitamin K 2/analogs & derivatives/chemistry ; *Water Microbiology ; }, abstract = {A pink-coloured bacterial strain, TAPP7T, was isolated from a freshwater creek in Taiwan. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain TAPP7T belonged to the genus Mucilaginibacter and showed highest similarity with Mucilaginibacter ginsengisoli B4Y-8T (97.6 %) and Mucilaginibacter carri PR0008KT (96.9 %). Cells of strain TAPP7T were Gram-staining-negative, aerobic, poly-β-hydroxybutyrate-accumulating and short-rod-shaped. Growth occurred at 10-30 °C (optimum, 15-20 °C), at pH 4-8 (optimum, pH 6) and with 0-1 % NaCl (optimum, 0.5 %). The predominant fatty acids were summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and iso-C15 : 0. The polar lipid profile consisted of phosphatidylethanolamine and several uncharacterized aminophospholipids and phospholipids. The major polyamine was homospermidine. The major isoprenoid quinone was MK-7. The DNA G+C content of the genomic DNA was 45.6 mol%. The DNA-DNA relatedness of strain TAPP7T with respect to Mucilaginibacter ginsengisoli B4Y-8T was less than 35 %. On the basis of the phylogenetic inference and phenotypic data, strain TAPP7T should be classified as a novel species, for which the name Mucilaginibacter amnicola sp. nov. is proposed. The type strain is TAPP7T (=BCRC 80976T=LMG 29556T=KCTC 52238T).}, } @article {pmid29219804, year = {2018}, author = {Huang, MM and Guo, LL and Wu, YH and Lai, QL and Shao, ZZ and Wang, CS and Wu, M and Xu, XW}, title = {Pseudooceanicola lipolyticus sp. nov., a marine alphaproteobacterium, reclassification of Oceanicola flagellatus as Pseudooceanicola flagellatus comb. nov. and emended description of the genus Pseudooceanicola.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {409-415}, doi = {10.1099/ijsem.0.002521}, pmid = {29219804}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Philippines ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; *Water Microbiology ; }, abstract = {A Gram-stain-negative, rod-shaped bacterium, designated 157T, was isolated from seawater collected from the Philippine Sea. Cells of strain 157T grew in medium containing 0.5-10.0 % NaCl (w/v, optimum 3 %), at pH 6.0-8.5 (optimum 7.0) and at 15-40 °C (optimum 30 °C). Tweens 20, 40 and 80 as well as urea were hydrolysed. The 16S rRNA gene sequence of strain 157T had a high sequence similarity with respect to Pseudooceanicola marinus AZO-CT (97.2 %), and exhibited less than 97.0 % sequence similarity to other type strains of the species with validly published names. Phylogenetic analyses revealed that strain 157T fell within a cluster comprising the Pseudooceanicola species and formed a coherent clade with P. marinus AZO-CT and Pseudooceanicola antarcticus Ar-45T. Strain 157T exhibited average nucleotide identity values of 74.5 and 74.9 % to P. marinus LMG 23705T and P. antarcticus Ar-45T, respectively. In silico DNA-DNA hybridization analysis revealed that strain 157T shared 20.2 % DNA relatedness with P. marinus LMG 23705T and 20.6 % with P. antarcticus Ar-45T, respectively. The sole isoprenoid quinone was ubiquinone 10. The major fatty acids were summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), C19 : 0 cyclo ω8c, C16 : 0 2-OH and C16 : 0. The major polar lipids were phosphatidylcholine, phosphatidylethanolamine, phosphatidylglycerol, one unidentified aminolipid and one unidentified glycolipid. The DNA G+C content was 64.6 mol%. According to the phylogenetic, chemotaxonomic and phenotypic data, it represents a novel species of the genus Pseudooceanicola, for which the name Pseudooceanicolalipolyticus is proposed. The type strain is 157T (=KCTC 52654T=MCCC 1K03317T). In addition, the description of the genus Pseudooceanicola is emended and Oceanicola flagellatus is reclassified as Pseudooceanicola flagellatus comb. nov., with the type strain DY470T (=CGMCC 1.12664T=LMG 27871T) proposed.}, } @article {pmid29218855, year = {2018}, author = {Arias-Sánchez, FI and Allen, RC and Hall, AR}, title = {Effects of prior exposure to antibiotics on bacterial adaptation to phages.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {277-286}, doi = {10.1111/jeb.13220}, pmid = {29218855}, issn = {1420-9101}, abstract = {Understanding adaptation to complex environments requires information about how exposure to one selection pressure affects adaptation to others. For bacteria, antibiotics and viral parasites (phages) are two of the most common selection pressures and are both relevant for treatment of bacterial infections: increasing antibiotic resistance is generating significant interest in using phages in addition or as an alternative to antibiotics. However, we lack knowledge of how exposure to antibiotics affects bacterial responses to phages. Specifically, it is unclear how the negative effects of antibiotics on bacterial population growth combine with any possible mutagenic effects or physiological responses to influence adaptation to other stressors such as phages, and how this net effect varies with antibiotic concentration. Here, we experimentally addressed the effect of pre-exposure to a wide range of antibiotic concentrations on bacterial responses to phages. Across 10 antibiotics, we found a strong association between their effects on bacterial population size and subsequent population growth in the presence of phages (which in these conditions indicates phage-resistance evolution). We detected some evidence of mutagenesis among populations treated with fluoroquinolones and β-lactams at sublethal doses, but these effects were small and not consistent across phage treatments. These results show that, although stressors such as antibiotics can boost adaptation to other stressors at low concentrations, these effects are weak compared to the effect of reduced population growth at inhibitory concentrations, which in our experiments strongly reduced the likelihood of subsequent phage-resistance evolution.}, } @article {pmid29218571, year = {2018}, author = {Rohini, S and Aswani, R and Kannan, M and Sylas, VP and Radhakrishnan, EK}, title = {Culturable Endophytic Bacteria of Ginger Rhizome and their Remarkable Multi-trait Plant Growth-Promoting Features.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {505-511}, pmid = {29218571}, issn = {1432-0991}, support = {010 - 40/FSHP/2010CSTE//KSCSTE - Fellowship/ ; 274/2015/KSCSTE dated 06/07/2015//KSCSTE- SRS/ ; }, mesh = {Bacteria/genetics/growth & development/*isolation & purification/metabolism ; Bacterial Proteins/genetics/metabolism ; Carbon-Carbon Lyases/genetics/metabolism ; Endophytes/genetics/growth & development/*isolation & purification/metabolism ; Ginger/growth & development/*microbiology ; Indoleacetic Acids/metabolism ; Nitrogen Fixation ; Phylogeny ; Rhizome/growth & development/*microbiology ; }, abstract = {Functional contribution of endophytic bacteria towards plant growth is highly impressive due to their species diversity and array of probiotic mechanisms. In the study, 96 endophytic bacteria isolated from rhizome of ginger (Zingiber officinale) were screened for phosphate solubilisation, 1-amino cyclopropane-1-carboxylate (ACC) deaminase activity, nitrogen fixation, ammonia and IAA production. Among these, sixteen endophytes with multiple plant growth-promoting activities were identified by 16S rDNA sequencing and all of them showed growth enhancement in Vigna unguiculata var Lola which make the study remarkably significant. The result was a clear indication of consistent, reliable and broad spectrum plant probiotic features of all the selected isolates. However, strain-specific effects on soil parameters represent the unique and distinguishable role of each of the selected isolates in the chemobiology of ginger rhizome. The study provided deeper insight into microbiomics of ginger rhizome with its agricultural promises.}, } @article {pmid29217587, year = {2018}, author = {Bae, T and Tomasini, L and Mariani, J and Zhou, B and Roychowdhury, T and Franjic, D and Pletikos, M and Pattni, R and Chen, BJ and Venturini, E and Riley-Gillis, B and Sestan, N and Urban, AE and Abyzov, A and Vaccarino, FM}, title = {Different mutational rates and mechanisms in human cells at pregastrulation and neurogenesis.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {550-555}, doi = {10.1126/science.aan8690}, pmid = {29217587}, issn = {1095-9203}, support = {P50 MH106934/MH/NIMH NIH HHS/United States ; R03 CA191421/CA/NCI NIH HHS/United States ; U01 MH106876/MH/NIMH NIH HHS/United States ; R01 MH100914/MH/NIMH NIH HHS/United States ; S10 RR029676/RR/NCRR NIH HHS/United States ; U01 MH106874/MH/NIMH NIH HHS/United States ; S10 RR019895/RR/NCRR NIH HHS/United States ; }, mesh = {Brain/*embryology ; Cell Lineage/genetics ; Gastrulation/*genetics ; Genome, Human ; Humans ; *Mosaicism ; *Mutagenesis ; Mutation ; *Mutation Rate ; Neoplasms/genetics ; Neurogenesis/*genetics ; Neurons ; Polymorphism, Single Nucleotide ; Single-Cell Analysis ; }, abstract = {Somatic mosaicism in the human brain may alter function of individual neurons. We analyzed genomes of single cells from the forebrains of three human fetuses (15 to 21 weeks postconception) using clonal cell populations. We detected 200 to 400 single-nucleotide variations (SNVs) per cell. SNV patterns resembled those found in cancer cell genomes, indicating a role of background mutagenesis in cancer. SNVs with a frequency of >2% in brain were also present in the spleen, revealing a pregastrulation origin. We reconstructed cell lineages for the first five postzygotic cleavages and calculated a mutation rate of ~1.3 mutations per division per cell. Later in development, during neurogenesis, the mutation spectrum shifted toward oxidative damage, and the mutation rate increased. Both neurogenesis and early embryogenesis exhibit substantially more mutagenesis than adulthood.}, } @article {pmid29217586, year = {2018}, author = {Zajac, DM and Sigillito, AJ and Russ, M and Borjans, F and Taylor, JM and Burkard, G and Petta, JR}, title = {Resonantly driven CNOT gate for electron spins.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6374}, pages = {439-442}, doi = {10.1126/science.aao5965}, pmid = {29217586}, issn = {1095-9203}, abstract = {Single-qubit rotations and two-qubit CNOT operations are crucial ingredients for universal quantum computing. Although high-fidelity single-qubit operations have been achieved using the electron spin degree of freedom, realizing a robust CNOT gate has been challenging because of rapid nuclear spin dephasing and charge noise. We demonstrate an efficient resonantly driven CNOT gate for electron spins in silicon. Our platform achieves single-qubit rotations with fidelities greater than 99%, as verified by randomized benchmarking. Gate control of the exchange coupling allows a quantum CNOT gate to be implemented with resonant driving in ~200 nanoseconds. We used the CNOT gate to generate a Bell state with 78% fidelity (corrected for errors in state preparation and measurement). Our quantum dot device architecture enables multi-qubit algorithms in silicon.}, } @article {pmid29217585, year = {2018}, author = {Chowell, D and Morris, LGT and Grigg, CM and Weber, JK and Samstein, RM and Makarov, V and Kuo, F and Kendall, SM and Requena, D and Riaz, N and Greenbaum, B and Carroll, J and Garon, E and Hyman, DM and Zehir, A and Solit, D and Berger, M and Zhou, R and Rizvi, NA and Chan, TA}, title = {Patient HLA class I genotype influences cancer response to checkpoint blockade immunotherapy.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {582-587}, pmid = {29217585}, issn = {1095-9203}, support = {K08 DE024774/DE/NIDCR NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA205426/CA/NCI NIH HHS/United States ; R01 CA208403/CA/NCI NIH HHS/United States ; }, mesh = {Adult ; Aged ; Antigen Presentation ; Antigens, Neoplasm/immunology ; CD8-Positive T-Lymphocytes/immunology ; CTLA-4 Antigen/*antagonists & inhibitors ; Cancer Vaccines/immunology/therapeutic use ; Cohort Studies ; Genetic Carrier Screening ; Histocompatibility Antigens Class I/chemistry/*genetics ; Humans ; Immunotherapy/*methods ; Melanoma/genetics/*immunology/mortality/*therapy ; Middle Aged ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; Protein Conformation ; Skin Neoplasms/genetics/*immunology/mortality/*therapy ; Treatment Outcome ; Young Adult ; }, abstract = {CD8+ T cell-dependent killing of cancer cells requires efficient presentation of tumor antigens by human leukocyte antigen class I (HLA-I) molecules. However, the extent to which patient-specific HLA-I genotype influences response to anti-programmed cell death protein 1 or anti-cytotoxic T lymphocyte-associated protein 4 is currently unknown. We determined the HLA-I genotype of 1535 advanced cancer patients treated with immune checkpoint blockade (ICB). Maximal heterozygosity at HLA-I loci ("A," "B," and "C") improved overall survival after ICB compared with patients who were homozygous for at least one HLA locus. In two independent melanoma cohorts, patients with the HLA-B44 supertype had extended survival, whereas the HLA-B62 supertype (including HLA-B*15:01) or somatic loss of heterozygosity at HLA-I was associated with poor outcome. Molecular dynamics simulations of HLA-B*15:01 revealed different elements that may impair CD8+ T cell recognition of neoantigens. Our results have important implications for predicting response to ICB and for the design of neoantigen-based therapeutic vaccines.}, } @article {pmid29217584, year = {2018}, author = {Lodato, MA and Rodin, RE and Bohrson, CL and Coulter, ME and Barton, AR and Kwon, M and Sherman, MA and Vitzthum, CM and Luquette, LJ and Yandava, CN and Yang, P and Chittenden, TW and Hatem, NE and Ryu, SC and Woodworth, MB and Park, PJ and Walsh, CA}, title = {Aging and neurodegeneration are associated with increased mutations in single human neurons.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6375}, pages = {555-559}, pmid = {29217584}, issn = {1095-9203}, support = {S10 RR028832/RR/NCRR NIH HHS/United States ; R01 NS032457/NS/NINDS NIH HHS/United States ; U01 MH106883/MH/NIMH NIH HHS/United States ; K99 AG054748/AG/NIA NIH HHS/United States ; K99 AG050749/AG/NIA NIH HHS/United States ; T32 HG002295/HG/NHGRI NIH HHS/United States ; T32 GM007753/GM/NIGMS NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; F30 MH102909/MH/NIMH NIH HHS/United States ; U54 HD090255/HD/NICHD NIH HHS/United States ; P50 MH106933/MH/NIMH NIH HHS/United States ; }, mesh = {Adolescent ; Adult ; Age Factors ; Aged ; Aged, 80 and over ; Aging/*genetics ; Child ; Child, Preschool ; Cockayne Syndrome/genetics ; DNA Mutational Analysis ; DNA Repair/*genetics ; Female ; Hippocampus/cytology/embryology ; Humans ; Infant ; Male ; Middle Aged ; *Mutation Rate ; Neurodegenerative Diseases/*genetics ; Neurogenesis/*genetics ; Neurons ; Prefrontal Cortex/cytology/embryology ; Single-Cell Analysis ; Whole Genome Sequencing ; Xeroderma Pigmentosum/genetics ; Young Adult ; }, abstract = {It has long been hypothesized that aging and neurodegeneration are associated with somatic mutation in neurons; however, methodological hurdles have prevented testing this hypothesis directly. We used single-cell whole-genome sequencing to perform genome-wide somatic single-nucleotide variant (sSNV) identification on DNA from 161 single neurons from the prefrontal cortex and hippocampus of 15 normal individuals (aged 4 months to 82 years), as well as 9 individuals affected by early-onset neurodegeneration due to genetic disorders of DNA repair (Cockayne syndrome and xeroderma pigmentosum). sSNVs increased approximately linearly with age in both areas (with a higher rate in hippocampus) and were more abundant in neurodegenerative disease. The accumulation of somatic mutations with age-which we term genosenium-shows age-related, region-related, and disease-related molecular signatures and may be important in other human age-associated conditions.}, } @article {pmid29217583, year = {2018}, author = {Yin, Y and Wu, M and Zubcevic, L and Borschel, WF and Lander, GC and Lee, SY}, title = {Structure of the cold- and menthol-sensing ion channel TRPM8.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {237-241}, pmid = {29217583}, issn = {1095-9203}, support = {DP2 EB020402/EB/NIBIB NIH HHS/United States ; R35 NS097241/NS/NINDS NIH HHS/United States ; S10 OD021634/OD/NIH HHS/United States ; }, mesh = {Animals ; Avian Proteins/*chemistry/metabolism/ultrastructure ; Binding Sites ; Cold Temperature ; Cryoelectron Microscopy ; Image Processing, Computer-Assisted ; Menthol/*metabolism ; Models, Molecular ; Passeriformes/*metabolism ; Protein Domains ; Protein Folding ; Protein Structure, Secondary ; Protein Subunits ; TRPM Cation Channels/*chemistry/metabolism/ultrastructure ; }, abstract = {Transient receptor potential melastatin (TRPM) cation channels are polymodal sensors that are involved in a variety of physiological processes. Within the TRPM family, member 8 (TRPM8) is the primary cold and menthol sensor in humans. We determined the cryo-electron microscopy structure of the full-length TRPM8 from the collared flycatcher at an overall resolution of ~4.1 ångstroms. Our TRPM8 structure reveals a three-layered architecture. The amino-terminal domain with a fold distinct among known TRP structures, together with the carboxyl-terminal region, forms a large two-layered cytosolic ring that extensively interacts with the transmembrane channel layer. The structure suggests that the menthol-binding site is located within the voltage-sensor-like domain and thus provides a structural glimpse of the design principle of the molecular transducer for cold and menthol sensation.}, } @article {pmid29217581, year = {2018}, author = {Autzen, HE and Myasnikov, AG and Campbell, MG and Asarnow, D and Julius, D and Cheng, Y}, title = {Structure of the human TRPM4 ion channel in a lipid nanodisc.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {228-232}, pmid = {29217581}, issn = {1095-9203}, support = {S10 OD021741/OD/NIH HHS/United States ; T32 GM008284/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; S10 OD020054/OD/NIH HHS/United States ; R01 NS047723/NS/NINDS NIH HHS/United States ; R01 GM098672/GM/NIGMS NIH HHS/United States ; }, mesh = {Binding Sites ; Calcium/chemistry/metabolism ; Cryoelectron Microscopy ; Humans ; Hydrophobic and Hydrophilic Interactions ; Lipids ; Models, Molecular ; Nanostructures ; Protein Conformation ; Protein Domains ; Protein Structure, Secondary ; Recombinant Proteins/chemistry/metabolism/ultrastructure ; TRPM Cation Channels/*chemistry/metabolism/ultrastructure ; }, abstract = {Transient receptor potential (TRP) melastatin 4 (TRPM4) is a widely expressed cation channel associated with a variety of cardiovascular disorders. TRPM4 is activated by increased intracellular calcium in a voltage-dependent manner but, unlike many other TRP channels, is permeable to monovalent cations only. Here we present two structures of full-length human TRPM4 embedded in lipid nanodiscs at ~3-angstrom resolution, as determined by single-particle cryo-electron microscopy. These structures, with and without calcium bound, reveal a general architecture for this major subfamily of TRP channels and a well-defined calcium-binding site within the intracellular side of the S1-S4 domain. The structures correspond to two distinct closed states. Calcium binding induces conformational changes that likely prime the channel for voltage-dependent opening.}, } @article {pmid29217396, year = {2018}, author = {Sutherland, WJ and Butchart, SHM and Connor, B and Culshaw, C and Dicks, LV and Dinsdale, J and Doran, H and Entwistle, AC and Fleishman, E and Gibbons, DW and Jiang, Z and Keim, B and Roux, XL and Lickorish, FA and Markillie, P and Monk, KA and Mortimer, D and Pearce-Higgins, JW and Peck, LS and Pretty, J and Seymour, CL and Spalding, MD and Tonneijck, FH and Gleave, RA}, title = {A 2018 Horizon Scan of Emerging Issues for Global Conservation and Biological Diversity.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {1}, pages = {47-58}, doi = {10.1016/j.tree.2017.11.006}, pmid = {29217396}, issn = {1872-8383}, mesh = {*Biodiversity ; *Conservation of Natural Resources ; *Ecosystem ; }, abstract = {This is our ninth annual horizon scan to identify emerging issues that we believe could affect global biological diversity, natural capital and ecosystem services, and conservation efforts. Our diverse and international team, with expertise in horizon scanning, science communication, as well as conservation science, practice, and policy, reviewed 117 potential issues. We identified the 15 that may have the greatest positive or negative effects but are not yet well recognised by the global conservation community. Themes among these topics include new mechanisms driving the emergence and geographic expansion of diseases, innovative biotechnologies, reassessments of global change, and the development of strategic infrastructure to facilitate global economic priorities.}, } @article {pmid29217371, year = {2018}, author = {Puvanendran, D and Cece, Q and Picard, M}, title = {Reconstitution of the activity of RND efflux pumps: a "bottom-up" approach.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {442-449}, doi = {10.1016/j.resmic.2017.11.004}, pmid = {29217371}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biological Transport ; Gram-Negative Bacteria/chemistry/genetics/*metabolism ; Liposomes/chemistry/metabolism ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; *Multigene Family ; }, abstract = {Efflux pumps are systems devoted to the extrusion of noxious compounds. In this review, we discuss the various strategies that have thus far been undertaken for the investigation of efflux pumps after reconstitution into liposomes. It is challenging to uncover mechanisms and dynamics of efflux pumps due to a number of characteristics: their function depends on the correct assembly of three components and they span two adjacent membranes whose lipid compositions are very different. In addition, efflux pumps are active transporters that need energy to work. We present possible lines of improvement for the study of such systems and provide insights into future goals and challenges of efflux pump reconstitution and transport.}, } @article {pmid29217262, year = {2018}, author = {Fuller, J}, title = {Universal etiology, multifactorial diseases and the constitutive model of disease classification.}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {67}, number = {}, pages = {8-15}, doi = {10.1016/j.shpsc.2017.11.002}, pmid = {29217262}, issn = {1879-2499}, mesh = {Communicable Diseases/*classification/*etiology ; Germ Theory of Disease/history ; History, 19th Century ; Humans ; *Models, Theoretical ; Philosophy, Medical/*history ; }, abstract = {Infectious diseases are often said to have a universal etiology, while chronic and noncommunicable diseases are said to be multifactorial in their etiology. It has been argued that the universal etiology of an infectious disease results from its classification using a monocausal disease model. In this article, I will reconstruct the monocausal model and argue that modern 'multifactorial diseases' are not monocausal by definition. 'Multifactorial diseases' are instead defined according to a constitutive disease model. On closer analysis, infectious diseases are also defined using the constitutive model rather than the monocausal model. As a result, our classification models alone cannot explain why infectious diseases have a universal etiology while chronic and noncommunicable diseases lack one. The explanation is instead provided by the Nineteenth Century germ theorists.}, } @article {pmid29217200, year = {2018}, author = {Rankin, SA and McCracken, KW and Luedeke, DM and Han, L and Wells, JM and Shannon, JM and Zorn, AM}, title = {Timing is everything: Reiterative Wnt, BMP and RA signaling regulate developmental competence during endoderm organogenesis.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {121-132}, pmid = {29217200}, issn = {1095-564X}, support = {R01 HL114898/HL/NHLBI NIH HHS/United States ; R01 HD073179/HD/NICHD NIH HHS/United States ; R01 DK070858/DK/NIDDK NIH HHS/United States ; U01 DK103117/DK/NIDDK NIH HHS/United States ; P01 HD093363/HD/NICHD NIH HHS/United States ; R01 HL098319/HL/NHLBI NIH HHS/United States ; R01 DK092456/DK/NIDDK NIH HHS/United States ; U19 AI116491/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bone Morphogenetic Proteins/*metabolism ; Endoderm/cytology/*embryology ; Human Embryonic Stem Cells/cytology/metabolism ; Humans ; Mice ; Mouse Embryonic Stem Cells/cytology/metabolism ; Organogenesis/*drug effects/physiology ; Somites/cytology/embryology ; Species Specificity ; Tretinoin/*pharmacology ; Wnt Proteins/*metabolism ; Xenopus Proteins/*metabolism ; Xenopus laevis ; }, abstract = {A small number of signaling pathways are used repeatedly during organogenesis, and they can have drastically different effects on the same population of cells depending on the embryonic stage. How cellular competence changes over developmental time is not well understood. Here we used Xenopus, mouse, and human pluripotent stem cells to investigate how the temporal sequence of Wnt, BMP, and retinoic acid (RA) signals regulates endoderm developmental competence and organ induction, focusing on respiratory fate. While Nkx2-1+ lung fate is not induced until late somitogenesis stages, here we show that lung competence is restricted by the gastrula stage as a result of Wnt and BMP-dependent anterior-posterior (A-P) patterning. These early Wnt and BMP signals make posterior endoderm refractory to subsequent RA/Wnt/BMP-dependent lung induction. We further mapped how RA modulates the response to Wnt and BMP in a temporal specific manner. In the gastrula RA promotes posterior identity, however in early somite stages of development RA regulates respiratory versus pharyngeal potential in anterior endoderm and midgut versus hindgut potential in posterior endoderm. Together our data suggest a dynamic and conserved response of vertebrate endoderm during organogenesis, wherein early Wnt/BMP/RA impacts how cells respond to later Wnt/BMP/RA signals, illustrating how reiterative combinatorial signaling can regulate both developmental competence and subsequent fate specification.}, } @article {pmid29216510, year = {2018}, author = {Orgeur, M and Brosch, R}, title = {Evolution of virulence in the Mycobacterium tuberculosis complex.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {68-75}, doi = {10.1016/j.mib.2017.11.021}, pmid = {29216510}, issn = {1879-0364}, mesh = {*Evolution, Molecular ; Genome, Bacterial ; Host-Pathogen Interactions/genetics/immunology ; Humans ; Mycobacterium tuberculosis/*genetics/immunology/*pathogenicity ; Phylogeny ; Tuberculosis/immunology/microbiology ; Virulence ; Virulence Factors/genetics ; }, abstract = {Mycobacterium tuberculosis, the causative agent of human tuberculosis is one of the most widely spread human pathogens. It has succeeded to infect a quarter of the global human population by developing most sophisticated ways to circumvent innate and adaptive immune defences. This highly specialized, major human pathogen has evolved from a pool of ancestral environmental mycobacteria, whose extant representatives are known under the name of Mycobacterium canettii. Recent whole genome analyses in combination with different phenotypic screens have provided key insights into the evolution of M. tuberculosis and closely related members regrouped in the M. tuberculosis complex (MTBC). They have also elucidated novel virulence determinants that are essential for these obligate pathogens. In this review, we present the most recent evolutionary models of the MTBC and various factors that have contributed to the outstanding evolutionary success of the tuberculosis agent.}, } @article {pmid29215213, year = {2018}, author = {Orsi, WD and Wilken, S and Del Campo, J and Heger, T and James, E and Richards, TA and Keeling, PJ and Worden, AZ and Santoro, AE}, title = {Identifying protist consumers of photosynthetic picoeukaryotes in the surface ocean using stable isotope probing.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {815-827}, doi = {10.1111/1462-2920.14018}, pmid = {29215213}, issn = {1462-2920}, abstract = {Photosynthetic picoeukaryotes contribute a significant fraction of primary production in the upper ocean. Micromonas pusilla is an ecologically relevant photosynthetic picoeukaryote, abundantly and widely distributed in marine waters. Grazing by protists may control the abundance of picoeukaryotes such as M. pusilla, but the diversity of the responsible grazers is poorly understood. To identify protists consuming photosynthetic picoeukaryotes in a productive North Pacific Ocean region, we amended seawater with living 15 N, 13 C-labelled M. pusilla cells in a 24-h replicated bottle experiment. DNA stable isotope probing, combined with high-throughput sequencing of V4 hypervariable regions from 18S rRNA gene amplicons (Tag-SIP), identified 19 operational taxonomic units (OTUs) of microbial eukaryotes that consumed M. pusilla. These OTUs were distantly related to cultured taxa within the dinoflagellates, ciliates, stramenopiles (MAST-1C and MAST-3 clades) and Telonema flagellates, thus, far known only from their environmental 18S rRNA gene sequences. Our discovery of eukaryotic prey consumption by MAST cells confirms that their trophic role in marine microbial food webs includes grazing upon picoeukaryotes. Our study provides new experimental evidence directly linking the genetic identity of diverse uncultivated microbial eukaryotes to the consumption of picoeukaryotic phytoplankton in the upper ocean.}, } @article {pmid29215193, year = {2018}, author = {Lowe-Power, TM and Hendrich, CG and von Roepenack-Lahaye, E and Li, B and Wu, D and Mitra, R and Dalsing, BL and Ricca, P and Naidoo, J and Cook, D and Jancewicz, A and Masson, P and Thomma, B and Lahaye, T and Michael, AJ and Allen, C}, title = {Metabolomics of tomato xylem sap during bacterial wilt reveals Ralstonia solanacearum produces abundant putrescine, a metabolite that accelerates wilt disease.}, journal = {Environmental microbiology}, volume = {20}, number = {4}, pages = {1330-1349}, pmid = {29215193}, issn = {1462-2920}, support = {T32 GM007215/GM/NIGMS NIH HHS/United States ; }, abstract = {Ralstonia solanacearum thrives in plant xylem vessels and causes bacterial wilt disease despite the low nutrient content of xylem sap. We found that R. solanacearum manipulates its host to increase nutrients in tomato xylem sap, enabling it to grow better in sap from infected plants than in sap from healthy plants. Untargeted GC/MS metabolomics identified 22 metabolites enriched in R. solanacearum-infected sap. Eight of these could serve as sole carbon or nitrogen sources for R. solanacearum. Putrescine, a polyamine that is not a sole carbon or nitrogen source for R. solanacearum, was enriched 76-fold to 37 µM in R. solanacearum-infected sap. R. solanacearum synthesized putrescine via a SpeC ornithine decarboxylase. A ΔspeC mutant required ≥ 15 µM exogenous putrescine to grow and could not grow alone in xylem even when plants were treated with putrescine. However, co-inoculation with wildtype rescued ΔspeC growth, indicating R. solanacearum produced and exported putrescine to xylem sap. Intriguingly, treating plants with putrescine before inoculation accelerated wilt symptom development and R. solanacearum growth and systemic spread. Xylem putrescine concentration was unchanged in putrescine-treated plants, so the exogenous putrescine likely accelerated disease indirectly by affecting host physiology. These results indicate that putrescine is a pathogen-produced virulence metabolite.}, } @article {pmid29215192, year = {2018}, author = {Liu, S and Wang, H and Deng, Y and Tian, P and Wang, Q}, title = {Forest conversion induces seasonal variation in microbial β-diversity.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {111-123}, doi = {10.1111/1462-2920.14017}, pmid = {29215192}, issn = {1462-2920}, abstract = {World-wide conversion of natural forests to other land uses has profound effects on soil microbial communities. However, how soil microbial β-diversity responds to land-use change and its driving mechanisms remains poorly understood. In this study, therefore, we examined the effect of forest conversion from native broad-leaved forest to coniferous plantation on soil microbial β-diversity and its underlying mechanisms in both summer and winter in subtropical China. Microbial communities increasingly differed in structure as geographical distance between them increased, and the slope of the relationship among distances and community similarity differed among forest covers. In general, as with microbial β-diversity, slopes also shifted across seasons. Finally, null deviations of bacterial and fungal communities were lower in coniferous plantation and presented opposing seasonal variations with greater influences of deterministic processes in summer for soil fungi and in winter for soil bacteria. Integrating previous frameworks with our β-null model results, we propose a conceptual model to link microbial secondary succession to stochastic/deterministic shifts in forest ecosystems. Overall, forest conversion induced significant increases in stochastic processes in both bacterial and fungal community assemblies. Therefore, our results highlight the importance of spatiotemporal scales to assess the influence of land-use change on microbial β-diversity.}, } @article {pmid29215190, year = {2018}, author = {Atashgahi, S and Häggblom, MM and Smidt, H}, title = {Organohalide respiration in pristine environments: implications for the natural halogen cycle.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {934-948}, doi = {10.1111/1462-2920.14016}, pmid = {29215190}, issn = {1462-2920}, abstract = {Halogenated organic compounds, also termed organohalogens, were initially considered to be of almost exclusively anthropogenic origin. However, over 5000 naturally synthesized organohalogens are known today. This has also fuelled the hypothesis that the natural and ancient origin of organohalogens could have primed development of metabolic machineries for their degradation, especially in microorganisms. Among these, a special group of anaerobic microorganisms was discovered that could conserve energy by reducing organohalogens as terminal electron acceptor in a process termed organohalide respiration. Originally discovered in a quest for biodegradation of anthropogenic organohalogens, these organohalide-respiring bacteria (OHRB) were soon found to reside in pristine environments, such as the deep subseafloor and Arctic tundra soil with limited/no connections to anthropogenic activities. As such, accumulating evidence suggests an important role of OHRB in local natural halogen cycles, presumably taking advantage of natural organohalogens. In this minireview, we integrate current knowledge regarding the natural origin and occurrence of industrially important organohalogens and the evolution and spread of OHRB, and describe potential implications for natural halogen and carbon cycles.}, } @article {pmid29215173, year = {2018}, author = {Barbosa, F and Rebar, D and Greenfield, MD}, title = {When do trade-offs occur? The roles of energy constraints and trait flexibility in bushcricket populations.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {287-301}, doi = {10.1111/jeb.13221}, pmid = {29215173}, issn = {1420-9101}, abstract = {In many animal species, the expression of sexually selected traits is negatively correlated with traits associated with survival such as immune function, a relationship termed a 'trade-off'. But an alternative in which sexually selected traits are positively correlated with survival traits is also widespread. We propose that the nature of intertrait relationships is largely determined by overall energy expenditure, energy availability and trait flexibility, with trade-offs expected when individuals are subject to energy constraints. We tested this hypothesis in Ephippiger diurnus, a European bushcricket in which males are distinguished by two prominent sexually selected traits, acoustic calls and a large spermatophore transferred to the female at mating, and where immune function may be critical in survival. Ephippiger diurnus are distributed as small, isolated populations that are differentiated genetically and behaviourally. We analysed songs, spermatophores and the immune function in male individuals from eight populations spanning a range of song types. As predicted, we only found trade-offs in those populations that expended more energy on song and were less flexible in their ability to adjust that expenditure. Ultimately, energy constraints and resulting trade-offs may limit the evolution of song exaggeration in E. diurnus populations broadcasting long calls comprised of multiple 'syllables'.}, } @article {pmid29214649, year = {2018}, author = {Sirkiä, PM and McFarlane, SE and Jones, W and Wheatcroft, D and Ålund, M and Rybinski, J and Qvarnström, A}, title = {Climate-driven build-up of temporal isolation within a recently formed avian hybrid zone.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {363-374}, doi = {10.1111/evo.13404}, pmid = {29214649}, issn = {1558-5646}, abstract = {Divergence in the onset of reproduction can act as an important source of reproductive isolation (i.e., allochronic isolation) between co-occurring young species, but evidence for the evolutionary processes leading to such divergence is often indirect. While advancing spring seasons strongly affect the onset of reproduction in many taxa, it remains largely unexplored whether contemporary spring advancement directly affects allochronic isolation between young species. We examined how increasing spring temperatures affected onset of reproduction and thereby hybridization between pied and collared flycatchers (Ficedula spp.) across habitat types in a young secondary contact zone. We found that both species have advanced their timing of breeding in 14 years. However, selection on pied flycatchers to breed earlier was weaker, resulting in a slower response to advancing springs compared to collared flycatchers and thereby build-up of allochronic isolation between the species. We argue that a preadaptation to a broader niche use (diet) of pied flycatchers explains the slower response to raising spring temperature, but that reduced risk to hybridize may contribute to further divergence in the onset of breeding in the future. Our results show that minor differences in the response to environmental change of co-occurring closely related species can quickly cause allochronic isolation.}, } @article {pmid29214647, year = {2018}, author = {Everman, ER and Morgan, TJ}, title = {Antagonistic pleiotropy and mutation accumulation contribute to age-related decline in stress response.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {303-317}, doi = {10.1111/evo.13408}, pmid = {29214647}, issn = {1558-5646}, abstract = {As organisms age, the effectiveness of natural selection weakens, leading to age-related decline in fitness-related traits. The evolution of age-related changes associated with senescence is likely influenced by mutation accumulation (MA) and antagonistic pleiotropy (AP). MA predicts that age-related decline in fitness components is driven by age-specific sets of alleles, nonnegative genetic correlations within trait across age, and an increase in the coefficient of genetic variance. AP predicts that age-related decline in a trait is driven by alleles with positive effects on fitness in young individuals and negative effects in old individuals, and is expected to lead to negative genetic correlations within traits across age. We build on these predictions using an association mapping approach to investigate the change in additive effects of SNPs across age and among traits for multiple stress-response fitness-related traits, including cold stress with and without acclimation and starvation resistance. We found support for both MA and AP theories of aging in the age-related decline in stress tolerance. Our study demonstrates that the evolution of age-related decline in stress tolerance is driven by a combination of alleles that have age-specific additive effects, consistent with MA, as well as nonindependent and antagonistic genetic architectures characteristic of AP.}, } @article {pmid29212065, year = {2018}, author = {Mitkus, M and Nevitt, GA and Kelber, A}, title = {Development of the Visual System in a Burrow-Nesting Seabird: Leach's Storm Petrel.}, journal = {Brain, behavior and evolution}, volume = {91}, number = {1}, pages = {4-16}, doi = {10.1159/000484080}, pmid = {29212065}, issn = {1421-9743}, abstract = {Little is known about the development of vision in wild birds. It is unknown, for example, whether the ability to see can be predicted by the level of prenatal growth or whether the eyes are open at hatching in a particular species. In this study, we investigated the growth of eyes, the formation of retinal ganglion cell topography, and the appearance of simple, visually guided behaviours in chicks of a small procellariiform seabird, Leach's storm petrel (Oceanodroma leucorhoa). This semi-precocial species, which has a well-developed sense of smell, nests in underground burrows where adults provision chicks for 6-8 weeks in the dark before fledging. Retinal ganglion cell topographic maps revealed that fine-tuning of cell distribution does not happen early in development, but rather that the ganglion cell layer continues to mature throughout provisioning and probably even after fledging. While the olfactory bulbs reached adult size around 7 weeks after hatching, the eyes and telencephalon continued to grow. Optokinetic head response and artificial burrow finding experiments indicated that chicks in the 2nd week after hatching lack even the most basic visually guided behaviours and are probably blind. Thus, vision in Leach's storm petrel chicks starts to function sometime around the 3rd week after hatching, well after the eyes have opened and the olfactory system is functional.}, } @article {pmid29211852, year = {2018}, author = {Graham, AM and Lavretsky, P and Muñoz-Fuentes, V and Green, AJ and Wilson, RE and McCracken, KG}, title = {Migration-Selection Balance Drives Genetic Differentiation in Genes Associated with High-Altitude Function in the Speckled Teal (Anas flavirostris) in the Andes.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {14-32}, pmid = {29211852}, issn = {1759-6653}, mesh = {*Acclimatization ; Adaptation, Physiological ; Altitude ; Animal Migration ; Animals ; Ducks/*genetics/*physiology ; *Gene Flow ; *Genetic Drift ; Polymorphism, Single Nucleotide ; Selection, Genetic ; }, abstract = {Local adaptation frequently occurs across populations as a result of migration-selection balance between divergent selective pressures and gene flow associated with life in heterogeneous landscapes. Studying the effects of selection and gene flow on the adaptation process can be achieved in systems that have recently colonized extreme environments. This study utilizes an endemic South American duck species, the speckled teal (Anas flavirostris), which has both high- and low-altitude populations. High-altitude speckled teal (A. f. oxyptera) are locally adapted to the Andean environment and mostly allopatric from low-altitude birds (A. f. flavirostris); however, there is occasional gene flow across altitudinal gradients. In this study, we used next-generation sequencing to explore genetic patterns associated with high-altitude adaptation in speckled teal populations, as well as the extent to which the balance between selection and migration have affected genetic architecture. We identified a set of loci with allele frequencies strongly correlated with altitude, including those involved in the insulin-like signaling pathway, bone morphogenesis, oxidative phosphorylation, responders to hypoxia-induced DNA damage, and feedback loops to the hypoxia-inducible factor pathway. These same outlier loci were found to have depressed gene flow estimates, as well as being highly concentrated on the Z-chromosome. Our results suggest a multifactorial response to life at high altitudes through an array of interconnected pathways that are likely under positive selection and whose genetic components seem to be providing an effective genomic barrier to interbreeding, potentially functioning as an avenue for population divergence and speciation.}, } @article {pmid29211721, year = {2018}, author = {Marrone, DP and Spilker, JS and Hayward, CC and Vieira, JD and Aravena, M and Ashby, MLN and Bayliss, MB and Béthermin, M and Brodwin, M and Bothwell, MS and Carlstrom, JE and Chapman, SC and Chen, CC and Crawford, TM and Cunningham, DJM and De Breuck, C and Fassnacht, CD and Gonzalez, AH and Greve, TR and Hezaveh, YD and Lacaille, K and Litke, KC and Lower, S and Ma, J and Malkan, M and Miller, TB and Morningstar, WR and Murphy, EJ and Narayanan, D and Phadke, KA and Rotermund, KM and Sreevani, J and Stalder, B and Stark, AA and Strandet, ML and Tang, M and Weiß, A}, title = {Galaxy growth in a massive halo in the first billion years of cosmic history.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {51-54}, pmid = {29211721}, issn = {1476-4687}, abstract = {According to the current understanding of cosmic structure formation, the precursors of the most massive structures in the Universe began to form shortly after the Big Bang, in regions corresponding to the largest fluctuations in the cosmic density field. Observing these structures during their period of active growth and assembly-the first few hundred million years of the Universe-is challenging because it requires surveys that are sensitive enough to detect the distant galaxies that act as signposts for these structures and wide enough to capture the rarest objects. As a result, very few such objects have been detected so far. Here we report observations of a far-infrared-luminous object at redshift 6.900 (less than 800 million years after the Big Bang) that was discovered in a wide-field survey. High-resolution imaging shows it to be a pair of extremely massive star-forming galaxies. The larger is forming stars at a rate of 2,900 solar masses per year, contains 270 billion solar masses of gas and 2.5 billion solar masses of dust, and is more massive than any other known object at a redshift of more than 6. Its rapid star formation is probably triggered by its companion galaxy at a projected separation of 8 kiloparsecs. This merging companion hosts 35 billion solar masses of stars and has a star-formation rate of 540 solar masses per year, but has an order of magnitude less gas and dust than its neighbour and physical conditions akin to those observed in lower-metallicity galaxies in the nearby Universe. These objects suggest the presence of a dark-matter halo with a mass of more than 100 billion solar masses, making it among the rarest dark-matter haloes that should exist in the Universe at this epoch.}, } @article {pmid29211709, year = {2018}, author = {Bañados, E and Venemans, BP and Mazzucchelli, C and Farina, EP and Walter, F and Wang, F and Decarli, R and Stern, D and Fan, X and Davies, FB and Hennawi, JF and Simcoe, RA and Turner, ML and Rix, HW and Yang, J and Kelson, DD and Rudie, GC and Winters, JM}, title = {An 800-million-solar-mass black hole in a significantly neutral Universe at a redshift of 7.5.}, journal = {Nature}, volume = {553}, number = {7689}, pages = {473-476}, pmid = {29211709}, issn = {1476-4687}, abstract = {Quasars are the most luminous non-transient objects known and as a result they enable studies of the Universe at the earliest cosmic epochs. Despite extensive efforts, however, the quasar ULAS J1120 + 0641 at redshift z = 7.09 has remained the only one known at z > 7 for more than half a decade. Here we report observations of the quasar ULAS J134208.10 + 092838.61 (hereafter J1342 + 0928) at redshift z = 7.54. This quasar has a bolometric luminosity of 4 × 1013 times the luminosity of the Sun and a black-hole mass of 8 × 108 solar masses. The existence of this supermassive black hole when the Universe was only 690 million years old-just five per cent of its current age-reinforces models of early black-hole growth that allow black holes with initial masses of more than about 104 solar masses or episodic hyper-Eddington accretion. We see strong evidence of absorption of the spectrum of the quasar redwards of the Lyman α emission line (the Gunn-Peterson damping wing), as would be expected if a significant amount (more than 10 per cent) of the hydrogen in the intergalactic medium surrounding J1342 + 0928 is neutral. We derive such a significant fraction of neutral hydrogen, although the exact fraction depends on the modelling. However, even in our most conservative analysis we find a fraction of more than 0.33 (0.11) at 68 per cent (95 per cent) probability, indicating that we are probing well within the reionization epoch of the Universe.}, } @article {pmid29211708, year = {2018}, author = {Liu, N and Lee, CH and Swigut, T and Grow, E and Gu, B and Bassik, MC and Wysocka, J}, title = {Selective silencing of euchromatic L1s revealed by genome-wide screens for L1 regulators.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {228-232}, pmid = {29211708}, issn = {1476-4687}, support = {R01 GM112720/GM/NIGMS NIH HHS/United States ; DP2 HD084069/HD/NICHD NIH HHS/United States ; R01 HG008150/HG/NHGRI NIH HHS/United States ; 1UM1HG009436-01/NH/NIH HHS/United States ; //Howard Hughes Medical Institute/United States ; T32 GM007790/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; CRISPR-Cas Systems/genetics ; Embryonic Stem Cells ; Euchromatin/*genetics ; *Gene Silencing ; Genome, Human/*genetics ; Genomics ; Humans ; K562 Cells ; Long Interspersed Nucleotide Elements/*genetics ; Male ; Mice ; Multiprotein Complexes/metabolism ; Nuclear Proteins/metabolism ; Phosphoproteins/metabolism ; Protein Subunits/metabolism ; Silencer Elements, Transcriptional/*genetics ; Transcription Factors/metabolism ; Transcription, Genetic ; }, abstract = {Transposable elements, also known as transposons, are now recognized not only as parasitic DNA, the spread of which in the genome must be controlled by the host, but also as major players in genome evolution and regulation. Long interspersed element-1 (LINE-1, also known as L1), the only currently autonomous mobile transposon in humans, occupies 17% of the genome and generates inter- and intra-individual genetic variation, in some cases resulting in disease. However, how L1 activity is controlled and the function of L1s in host gene regulation are not completely understood. Here we use CRISPR-Cas9 screening strategies in two distinct human cell lines to provide a genome-wide survey of genes involved in the control of L1 retrotransposition. We identify functionally diverse genes that either promote or restrict L1 retrotransposition. These genes, which are often associated with human diseases, control the L1 life cycle at the transcriptional or the post-transcriptional level in a manner that can depend on the endogenous L1 nucleotide sequence, underscoring the complexity of L1 regulation. We further investigate the restriction of L1 by the protein MORC2 and by the human silencing hub (HUSH) complex subunits MPP8 and TASOR. HUSH and MORC2 can selectively bind evolutionarily young, full-length L1s located within transcriptionally permissive euchromatic environments, and promote deposition of histone H3 Lys9 trimethylation (H3K9me3) for transcriptional silencing. Notably, these silencing events often occur within introns of transcriptionally active genes, and lead to the downregulation of host gene expression in a HUSH-, MORC2-, and L1-dependent manner. Together, these results provide a rich resource for studies of L1 retrotransposition, elucidate a novel L1 restriction pathway and illustrate how epigenetic silencing of transposable elements rewires host gene expression programs.}, } @article {pmid29210448, year = {2018}, author = {Kuijper, B and Johnstone, RA}, title = {Maternal effects and parent-offspring conflict.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {220-233}, doi = {10.1111/evo.13403}, pmid = {29210448}, issn = {1558-5646}, abstract = {Maternal effects can provide offspring with reliable information about the environment they are likely to experience, but also offer scope for maternal manipulation of young when interests diverge between parents and offspring. To predict the impact of parent-offspring conflict, we model the evolution of maternal effects on local adaptation of young. We find that parent-offspring conflict strongly influences the stability of maternal effects; moreover, the nature of the disagreement between parents and young predicts how conflict is resolved: when mothers favor less extreme mixtures of phenotypes relative to offspring (i.e., when mothers stand to gain by hedging their bets), mothers win the conflict by providing offspring with limited amounts of information. When offspring favor overproduction of one and the same phenotype across all environments compared to mothers (e.g., when offspring favor a larger body size), neither side wins the conflict and signaling breaks down. Only when offspring favor less extreme mixtures relative to their mothers (something no current model predicts), offspring win the conflict and obtain full information about the environment. We conclude that a partial or complete breakdown of informative maternal effects will be the norm rather than the exception in the presence of parent-offspring conflict.}, } @article {pmid29210213, year = {2018}, author = {Madec, C}, title = {Digest: The effect of the pollinator composition and abundance on pollen-related floral traits.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {215-216}, doi = {10.1111/evo.13405}, pmid = {29210213}, issn = {1558-5646}, } @article {pmid29209822, year = {2018}, author = {Nguyen, LTT and Takemura, AJ and Ohniwa, RL and Saito, S and Morikawa, K}, title = {Sodium Polyanethol Sulfonate Modulates Natural Transformation of SigH-Expressing Staphylococcus aureus.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {499-504}, pmid = {29209822}, issn = {1432-0991}, mesh = {Bacterial Proteins/genetics/metabolism ; Gene Expression Regulation, Bacterial/drug effects ; Polyanetholesulfonate/*pharmacology ; Staphylococcus aureus/*drug effects/genetics/metabolism ; Transformation, Genetic/*drug effects ; }, abstract = {Expression of genes required for natural genetic competence in Staphylococcus aureus is controlled by an alternative transcription sigma factor, SigH. However, even in the SigH-expressing cells, the DNA transformation efficiency varies depending on culture conditions. We report here that cells grown in the competence-inducing medium (CS2 medium) exhibit enlarged morphology with disintegrated cell walls. Notably, an autolysis inhibitor, Sodium Polyanethol Sulfonate (SPS), facilitated transformation in CS2 medium in a dose-dependent manner, suggesting the involvement of the cell wall metabolism in transformation. However, the transformation efficiency of cells grown in TSB was not improved by physical or enzymatic damage on the cell walls.}, } @article {pmid29209821, year = {2018}, author = {Luo, Z and Xie, X and Qi, Y and Wu, Y}, title = {Hemolytic Escherichia coli Inhibits Swarming and Differentiation of Proteus mirabilis.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {471-475}, pmid = {29209821}, issn = {1432-0991}, support = {JY201713//the New Xiangya Talent Project of The Third Xiangya Hospital of Central South University/ ; }, mesh = {Antibiosis ; Escherichia coli/*physiology ; Proteus mirabilis/*cytology/physiology ; }, abstract = {Swarming is a hallmark of Proteus mirabilis, whether common gram-negative bacilli affect the swarming of P. mirabilis is still unclear. In this study, we found that P. mirabilis swarming was inhibited by Escherichia coli ATCC25922, but was not affected by Klebsiella pneumoniae, Acinetobacter baumannii, or Pseudomonas aeruginosa strains. The migration distance of P. mirabilis when mixed with E. coli ATCC25922 was strongly reduced, and the inhibition of the swarming of P. mirabilis by E. coli ATCC25922 was dependent on cell density. In addition, initiation of P. mirabilis swarming was delayed by E. coli ATCC25922. Among clinical isolates, including gram-negative bacilli and gram-positive cocci, only hemolytic E. coli inhibited the swarming of P. mirabilis. In summary, hemolytic E. coli inhibited the swarming and differentiation of P. mirabilis.}, } @article {pmid29209820, year = {2018}, author = {Ten, LN and Okiria, J and Lee, JJ and Lee, SY and Park, S and Lee, DS and Kang, IK and Kim, MK and Jung, HY}, title = {Spirosoma terrae sp. nov., Isolated from Soil from Jeju Island, Korea.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {492-498}, pmid = {29209820}, issn = {1432-0991}, support = {NRF-2014H1C1A1066929//the Human Resource Training Program for Regional Innovation and Creativity through the Ministry of Education and National Research Foundation (NRF) of Korea/ ; grant 162S-4-3-1727//the Brain Pool Program of 2016 through the Korean Federation of Science and Technology Societies (KOFST) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea/ ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/classification/genetics/*isolation & purification/metabolism ; DNA, Bacterial/genetics ; Fatty Acids/chemistry/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Soil/chemistry ; *Soil Microbiology ; }, abstract = {The taxonomic position of bacterial strain, designated 15J9-4T, recovered from a beach soil sample on Jeju Island, South Korea, was established using a polyphasic approach. Strain 15J9-4T was assigned to phylum Bacteroidetes within the family Cytophagaceae based on 16S rRNA gene similarities. The closest phylogenetic relatives with validly published names were Spirosoma panaciterrae Gsoil 1519T (94.2% similarity) and Spirosoma luteolum 16F6ET (94.1%). Cells were rod-shaped, Gram-stain-negative, and non-motile. The isolate grew on NA, R2A, TSA, and LB agar. The temperature limits for growth were 10 and 30 °C with an optimum at 25 °C and the pH range was 7-8. Menaquinone MK-7 was the predominant respiratory quinone. The major cellular fatty acids comprised summed feature 3 (C16:1 ω6c/C16:1 ω7c, 30.2%), C16:1 ω5c (22.2%), iso C15:0 (12.9%), and C16:0 (8.8%). Phosphatidylethanolamine was identified as the major polar lipid. The G+C content of the genomic DNA was 48.4 mol%. The results obtained from the polyphasic analyses allowed for the genotypic and phenotypic differentiation of strain 15J9-4T from recognized Spirosoma species. Therefore, the isolate is considered to represent a novel species in the genus Spirosoma, for which the name Spirosoma terrae sp. nov. is proposed. The type strain is 15J9-4T (= KCTC 52035T = JCM 31994T).}, } @article {pmid29208994, year = {2018}, author = {Roll, U and Feldman, A and Novosolov, M and Allison, A and Bauer, AM and Bernard, R and Böhm, M and Castro-Herrera, F and Chirio, L and Collen, B and Colli, GR and Dabool, L and Das, I and Doan, TM and Grismer, LL and Hoogmoed, M and Itescu, Y and Kraus, F and LeBreton, M and Lewin, A and Martins, M and Maza, E and Meirte, D and Nagy, ZT and Nogueira, CC and Pauwels, OSG and Pincheira-Donoso, D and Powney, GD and Sindaco, R and Tallowin, O and Torres-Carvajal, O and Trape, JF and Vidan, E and Uetz, P and Wagner, P and Wang, Y and Orme, CDL and Grenyer, R and Meiri, S}, title = {Author Correction: The global distribution of tetrapods reveals a need for targeted reptile conservation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {193}, doi = {10.1038/s41559-017-0399-9}, pmid = {29208994}, issn = {2397-334X}, } @article {pmid29208993, year = {2018}, author = {Fox, KCR and Muthukrishna, M and Shultz, S}, title = {Author Correction: The social and cultural roots of whale and dolphin brains.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {195}, doi = {10.1038/s41559-017-0408-z}, pmid = {29208993}, issn = {2397-334X}, abstract = {In Table 1 of the Supplementary Information, the data presented in the column 'Corrected social repertoire' were incorrect. This error does not affect the analyses, statistics or conclusions of the study, which employed the correct values. The data have now been corrected in the Supplementary file.}, } @article {pmid29208992, year = {2018}, author = {Frachon, L and Libourel, C and Villoutreix, R and Carrère, S and Glorieux, C and Huard-Chauveau, C and Navascués, M and Gay, L and Vitalis, R and Baron, E and Amsellem, L and Bouchez, O and Vidal, M and Le Corre, V and Roby, D and Bergelson, J and Roux, F}, title = {Author Correction: Intermediate degrees of synergistic pleiotropy drive adaptive evolution in ecological time.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {194}, doi = {10.1038/s41559-017-0405-2}, pmid = {29208992}, issn = {2397-334X}, abstract = {In the version of this Article previously published, there was a typographical error ('4' instead of '2') in the equations relating F ST and effective population size (N e) in the Methods section 'Genome-wide scan for selection based on temporal differentiation'. The correct equations are given below.[Formula: see text] [Formula: see text].}, } @article {pmid29208713, year = {2018}, author = {Wendel, BM and Cole, JM and Courcelle, CT and Courcelle, J}, title = {SbcC-SbcD and ExoI process convergent forks to complete chromosome replication.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {2}, pages = {349-354}, pmid = {29208713}, issn = {1091-6490}, support = {R15 ES025953/ES/NIEHS NIH HHS/United States ; }, mesh = {Chromosomes, Bacterial/genetics ; DNA Breaks, Double-Stranded ; DNA Repair ; *DNA Replication ; DNA, Bacterial/genetics/*metabolism ; Deoxyribonucleases/genetics/*metabolism ; Escherichia coli Proteins/genetics/*metabolism ; Exodeoxyribonucleases/genetics/*metabolism ; Exonucleases/genetics/*metabolism ; Models, Genetic ; }, abstract = {SbcC-SbcD are the bacterial orthologs of Mre11-Rad50, a nuclease complex essential for genome stability, normal development, and viability in mammals. In vitro, these enzymes degrade long DNA palindromic structures. When inactivated along with ExoI in Escherichia coli, or Sae2 in eukaryotes, palindromic amplifications arise and propagate in cells. However, long DNA palindromes are not normally found in bacterial or human genomes, leaving the cellular substrates and function of these enzymes unknown. Here, we show that during the completion of DNA replication, convergent replication forks form a palindrome-like structural intermediate that requires nucleolytic processing by SbcC-SbcD and ExoI before chromosome replication can be completed. Inactivation of these nucleases prevents completion from occurring, and under these conditions, cells maintain viability by shunting the reaction through an aberrant recombinational pathway that leads to amplifications and instability in this region. The results identify replication completion as an event critical to maintain genome integrity and cell viability, demonstrate SbcC-SbcD-ExoI acts before RecBCD and is required to initiate the completion reaction, and reveal how defects in completion result in genomic instability.}, } @article {pmid29208711, year = {2018}, author = {Sun, Y and Zhang, Y and Hamilton, K and Manley, JL and Shi, Y and Walz, T and Tong, L}, title = {Molecular basis for the recognition of the human AAUAAA polyadenylation signal.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {7}, pages = {E1419-E1428}, pmid = {29208711}, issn = {1091-6490}, support = {R35 GM118136/GM/NIGMS NIH HHS/United States ; R01 GM090056/GM/NIGMS NIH HHS/United States ; P41 GM103310/GM/NIGMS NIH HHS/United States ; S10 OD019994/OD/NIH HHS/United States ; R35 GM118093/GM/NIGMS NIH HHS/United States ; }, mesh = {Cleavage And Polyadenylation Specificity Factor/chemistry/*metabolism ; Cryoelectron Microscopy ; Humans ; Models, Molecular ; Nuclear Proteins/chemistry/*metabolism ; Poly A/chemistry/*metabolism ; *Polyadenylation ; Protein Conformation ; RNA Precursors/chemistry/*metabolism ; RNA, Messenger/chemistry/*metabolism ; }, abstract = {Nearly all eukaryotic messenger RNA precursors must undergo cleavage and polyadenylation at their 3'-end for maturation. A crucial step in this process is the recognition of the AAUAAA polyadenylation signal (PAS), and the molecular mechanism of this recognition has been a long-standing problem. Here, we report the cryo-electron microscopy structure of a quaternary complex of human CPSF-160, WDR33, CPSF-30, and an AAUAAA RNA at 3.4-Å resolution. Strikingly, the AAUAAA PAS assumes an unusual conformation that allows this short motif to be bound directly by both CPSF-30 and WDR33. The A1 and A2 bases are recognized specifically by zinc finger 2 (ZF2) of CPSF-30 and the A4 and A5 bases by ZF3. Interestingly, the U3 and A6 bases form an intramolecular Hoogsteen base pair and directly contact WDR33. CPSF-160 functions as an essential scaffold and preorganizes CPSF-30 and WDR33 for high-affinity binding to AAUAAA. Our findings provide an elegant molecular explanation for how PAS sequences are recognized for mRNA 3'-end formation.}, } @article {pmid29208490, year = {2018}, author = {Masi, M and Dumont, E and Vergalli, J and Pajovic, J and Réfrégiers, M and Pagès, JM}, title = {Fluorescence enlightens RND pump activity and the intrabacterial concentration of antibiotics.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {432-441}, doi = {10.1016/j.resmic.2017.11.005}, pmid = {29208490}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/*analysis/metabolism ; Bacterial Proteins/*chemistry/genetics/*metabolism ; Biological Transport ; Fluorescence ; Gram-Negative Bacteria/chemistry/genetics/*metabolism ; Membrane Transport Proteins/*chemistry/genetics/*metabolism ; *Multigene Family ; }, abstract = {To understand antibiotic resistance in Gram-negative bacteria, a key point is to investigate antibiotic accumulation, which is defined by influx and efflux. Several methods exist to evaluate membrane permeability and efflux pump activity, but they present disadvantages and limitations. An optimized spectrofluorimetric method using intrinsic tryptophan fluorescence as an internal standard, as well as a complementary microfluorimetric assay following time-course accumulation in intact individual cells, have been developed. Comparing the latter population and single cell approaches can lead to an understanding of phenotypic heterogeneity within a population. The two methodologies lead to determination of parameters, concentration, accumulation rates and localization that contribute to emerging concepts (RTC2T, SICAR) with the aim of identifying and detailing antibiotic chemotypes involved in influx/efflux.}, } @article {pmid29208373, year = {2018}, author = {Hino, H and Nakanishi, A and Seki, R and Aoki, T and Yamaha, E and Kawahara, A and Shimizu, T and Hibi, M}, title = {Roles of maternal wnt8a transcripts in axis formation in zebrafish.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {96-107}, doi = {10.1016/j.ydbio.2017.11.016}, pmid = {29208373}, issn = {1095-564X}, mesh = {Animals ; Animals, Genetically Modified/embryology/genetics ; Cytoskeletal Proteins/genetics/*metabolism ; Embryo, Nonmammalian/*embryology ; Open Reading Frames/*physiology ; RNA, Messenger/genetics/*metabolism ; Wnt Proteins/genetics/*metabolism ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {In early zebrafish development, the program for dorsal axis formation begins soon after fertilization. Previous studies suggested that dorsal determinants (DDs) localize to the vegetal pole, and are transported to the dorsal blastomeres in a microtubule-dependent manner. The DDs activate the canonical Wnt pathway and induce dorsal-specific genes that are required for dorsal axis formation. Among wnt-family genes, only the wnt8a mRNA is reported to localize to the vegetal pole in oocytes and to induce the dorsal axis, suggesting that Wnt8a is a candidate DD. Here, to reveal the roles of maternal wnt8a, we generated wnt8a mutants by transcription activator-like effector nucleases (TALENs), and established zygotic, maternal, and maternal zygotic wnt8a mutants by germ-line replacement. Zebrafish wnt8a has two open reading frames (ORF1 and ORF2) that are tandemly located in the genome. Although the zygotic ORF1 or ORF2 wnt8a mutants showed little or no axis-formation defects, the ORF1/2 compound mutants showed antero-dorsalized phenotypes, indicating that ORF1 and ORF2 have redundant roles in ventrolateral and posterior tissue formation. Unexpectedly, the maternal wnt8a ORF1/2 mutants showed no axis-formation defects. The maternal-zygotic wnt8a ORF1/2 mutants showed more severe antero-dorsalized phenotypes than the zygotic mutants. These results indicated that maternal wnt8a is dispensable for the initial dorsal determination, but cooperates with zygotic wnt8a for ventrolateral and posterior tissue formation. Finally, we re-examined the maternal wnt genes and found that Wnt6a is an alternative candidate DD.}, } @article {pmid29207313, year = {2018}, author = {Kusmierek, M and Dersch, P}, title = {Regulation of host-pathogen interactions via the post-transcriptional Csr/Rsm system.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {58-67}, doi = {10.1016/j.mib.2017.11.022}, pmid = {29207313}, issn = {1879-0364}, mesh = {Bacteria/*genetics/pathogenicity ; Bacterial Proteins/*genetics/metabolism ; Escherichia coli Proteins/metabolism ; *Gene Expression Regulation, Bacterial ; Host-Pathogen Interactions/*genetics ; Humans ; *RNA Processing, Post-Transcriptional ; RNA, Messenger/metabolism ; RNA-Binding Proteins/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; Virulence/genetics ; Virulence Factors/metabolism ; }, abstract = {A successful colonization of specific hosts requires a rapid and efficient adaptation of the virulence-relevant gene expression program by bacterial pathogens. An important element in this endeavor is the Csr/Rsm system. This multi-component, post-transcriptional control system forms a central hub within complex regulatory networks and coordinately adjusts virulence properties with metabolic and physiological attributes of the pathogen. A key function is elicited by the RNA-binding protein CsrA/RsmA. CsrA/RsmA interacts with numerous target mRNAs, many of which encode crucial virulence factors, and alters their translation, stability or elongation of transcription. Recent studies highlighted that important colonization factors, toxins, and bacterial secretion systems are under CsrA/RsmA control. CsrA/RsmA deficiency impairs host colonization and attenuates virulence, making this post-transcriptional regulator a suitable drug target. The CsrA/RsmA protein can be inactivated through sequestration by non-coding RNAs, or via binding to specific highly abundant mRNAs and interacting proteins. The wide range of interaction partners and RNA targets, as well as the overarching, interlinked genetic control circuits illustrate the complexity of this regulatory system in the different pathogens. Future work addressing spatio-temporal changes of Csr/Rsm-mediated control during the course of an infection will help us to understand how bacteria reprogram their expression profile to cope with continuous changes experienced in colonized niches.}, } @article {pmid29207308, year = {2018}, author = {Oyserman, BO and Medema, MH and Raaijmakers, JM}, title = {Road MAPs to engineer host microbiomes.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {46-54}, doi = {10.1016/j.mib.2017.11.023}, pmid = {29207308}, issn = {1879-0364}, mesh = {Animals ; Genetic Engineering/*methods ; Host Microbial Interactions/*genetics ; Humans ; Microbial Consortia/*genetics ; Microbiota/genetics ; Phenotype ; Probiotics ; }, abstract = {Microbiomes contribute directly or indirectly to host health and fitness. Thus far, investigations into these emergent traits, referred to here as microbiome-associated phenotypes (MAPs), have been primarily qualitative and taxonomy-driven rather than quantitative and trait-based. We present the MAPs-first approach, a theoretical and experimental roadmap that involves quantitative profiling of MAPs across genetically variable hosts and subsequent identification of the underlying mechanisms. We outline strategies for developing 'modular microbiomes'-synthetic microbial consortia that are engineered in concert with the host genotype to confer different but mutually compatible MAPs to a single host or host population. By integrating host and microbial traits, these strategies will facilitate targeted engineering of microbiomes to the benefit of agriculture, human/animal health and biotechnology.}, } @article {pmid29206933, year = {2018}, author = {Caspermeyer, J}, title = {Scientists Bring New Insights into the Heritability of HIV Infection Severity.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {257}, doi = {10.1093/molbev/msx290}, pmid = {29206933}, issn = {1537-1719}, } @article {pmid29206931, year = {2018}, author = {Caspermeyer, J}, title = {Scientists Find Evidence Our Best Friends, Dogs, Similarly Adapted to Malaria in Africa.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {523}, doi = {10.1093/molbev/msx289}, pmid = {29206931}, issn = {1537-1719}, mesh = {Acclimatization ; Africa ; Animals ; Dogs ; *Friends ; Malaria ; *Parasites ; }, } @article {pmid29206930, year = {2018}, author = {Caspermeyer, J}, title = {Exploring an Ancient Event in Pumpkin, Gourd, and Melon Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {256-257}, doi = {10.1093/molbev/msx291}, pmid = {29206930}, issn = {1537-1719}, } @article {pmid29206925, year = {2018}, author = {de Bruijn, I and Liu, Y and Wiegertjes, GF and Raaijmakers, JM}, title = {Exploring fish microbial communities to mitigate emerging diseases in aquaculture.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix161}, pmid = {29206925}, issn = {1574-6941}, abstract = {Aquaculture is the fastest growing animal food sector worldwide and expected to further increase to feed the growing human population. However, existing and (re-)emerging diseases are hampering fish and shellfish cultivation and yield. For many diseases, vaccination protocols are not in place and the excessive use of antibiotics and other chemicals is of substantial concern. A more sustainable disease control strategy to protect fish and shellfish from (re-)emerging diseases could be achieved by introduction or augmentation of beneficial microbes. To establish and maintain a 'healthy' fish microbiome, a fundamental understanding of the diversity and temporal-spatial dynamics of fish-associated microbial communities and their impact on growth and health of their aquatic hosts is required. This review describes insights in the diversity and functions of the fish bacterial communities elucidated with next-generation sequencing and discusses the potential of the microbes to mitigate (re-)emerging diseases in aquaculture.}, } @article {pmid29206918, year = {2018}, author = {Mentes, A and Szabó, A and Somogyi, B and Vajna, B and Tugyi, N and Csitári, B and Vörös, L and Felföldi, T}, title = {Differences in planktonic microbial communities associated with three types of macrophyte stands in a shallow lake.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix164}, pmid = {29206918}, issn = {1574-6941}, abstract = {Little is known about how various substances from living and decomposing aquatic macrophytes affect the horizontal patterns of planktonic bacterial communities. Study sites were located within Lake Kolon, which is a freshwater marsh and can be characterised by open-water sites and small ponds with different macrovegetation (Phragmites australis, Nymphea alba and Utricularia vulgaris). Our aim was to reveal the impact of these macrophytes on the composition of the planktonic microbial communities using comparative analysis of environmental parameters, microscopy and pyrosequencing data. Bacterial 16S rRNA gene sequences were dominated by members of phyla Proteobacteria (36%-72%), Bacteroidetes (12%-33%) and Actinobacteria (5%-26%), but in the anoxic sample the ratio of Chlorobi (54%) was also remarkable. In the phytoplankton community, Cryptomonas sp., Dinobryon divergens, Euglena acus and chrysoflagellates had the highest proportion. Despite the similarities in most of the measured environmental parameters, the inner ponds had different bacterial and algal communities, suggesting that the presence and quality of macrophytes directly and indirectly controlled the composition of microbial plankton.}, } @article {pmid29206915, year = {2018}, author = {Peri, S and Kulkarni, A and Feyertag, F and Berninsone, PM and Alvarez-Ponce, D}, title = {Phylogenetic Distribution of CMP-Neu5Ac Hydroxylase (CMAH), the Enzyme Synthetizing the Proinflammatory Human Xenoantigen Neu5Gc.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {207-219}, pmid = {29206915}, issn = {1759-6653}, support = {P20 GM103440/GM/NIGMS NIH HHS/United States ; P20 GM103554/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Biosynthetic Pathways ; Humans ; Mixed Function Oxygenases/*genetics/metabolism ; Molecular Sequence Annotation ; Neuraminic Acids/*metabolism ; *Phylogeny ; Pseudogenes ; }, abstract = {The enzyme CMP-N-acetylneuraminic acid hydroxylase (CMAH) is responsible for the synthesis of N-glycolylneuraminic acid (Neu5Gc), a sialic acid present on the cell surface proteins of most deuterostomes. The CMAH gene is thought to be present in most deuterostomes, but it has been inactivated in a number of lineages, including humans. The inability of humans to synthesize Neu5Gc has had several evolutionary and biomedical implications. Remarkably, Neu5Gc is a xenoantigen for humans, and consumption of Neu5Gc-containing foods, such as red meats, may promote inflammation, arthritis, and cancer. Likewise, xenotransplantation of organs producing Neu5Gc can result in inflammation and organ rejection. Therefore, knowing what animal species contain a functional CMAH gene, and are thus capable of endogenous Neu5Gc synthesis, has potentially far-reaching implications. In addition to humans, other lineages are known, or suspected, to have lost CMAH; however, to date reports of absent and pseudogenic CMAH genes are restricted to a handful of species. Here, we analyze all available genomic data for nondeuterostomes, and 322 deuterostome genomes, to ascertain the phylogenetic distribution of CMAH. Among nondeuterostomes, we found CMAH homologs in two green algae and a few prokaryotes. Within deuterostomes, putatively functional CMAH homologs are present in 184 of the studied genomes, and a total of 31 independent gene losses/pseudogenization events were inferred. Our work produces a list of animals inferred to be free from endogenous Neu5Gc based on the absence of CMAH homologs and are thus potential candidates for human consumption, xenotransplantation research, and model organisms for investigation of human diseases.}, } @article {pmid29205750, year = {2018}, author = {Fortunato, CS and Larson, B and Butterfield, DA and Huber, JA}, title = {Spatially distinct, temporally stable microbial populations mediate biogeochemical cycling at and below the seafloor in hydrothermal vent fluids.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {769-784}, doi = {10.1111/1462-2920.14011}, pmid = {29205750}, issn = {1462-2920}, abstract = {At deep-sea hydrothermal vents, microbial communities thrive across geochemical gradients above, at, and below the seafloor. In this study, we determined the gene content and transcription patterns of microbial communities and specific populations to understand the taxonomy and metabolism both spatially and temporally across geochemically different diffuse fluid hydrothermal vents. Vent fluids were examined via metagenomic, metatranscriptomic, genomic binning, and geochemical analyses from Axial Seamount, an active submarine volcano on the Juan de Fuca Ridge in the NE Pacific Ocean, from 2013 to 2015 at three different vents: Anemone, Marker 33, and Marker 113. Results showed that individual vent sites maintained microbial communities and specific populations over time, but with spatially distinct taxonomic, metabolic potential, and gene transcription profiles. The geochemistry and physical structure of each vent both played important roles in shaping the dominant organisms and metabolisms present at each site. Genomic binning identified key populations of SUP05, Aquificales and methanogenic archaea carrying out important transformations of carbon, sulfur, hydrogen, and nitrogen, with groups that appear unique to individual sites. This work highlights the connection between microbial metabolic processes, fluid chemistry, and microbial population dynamics at and below the seafloor and increases understanding of the role of hydrothermal vent microbial communities in deep ocean biogeochemical cycles.}, } @article {pmid29205137, year = {2018}, author = {Lee, SD}, title = {Maribius pontilimi sp. nov., isolated from a tidal mudflat.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {353-357}, doi = {10.1099/ijsem.0.002512}, pmid = {29205137}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Islands ; Nucleic Acid Hybridization ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel marine Gram-negative bacterium, designated strain GH1-23T, was isolated from a tidal mudflat sample collected at Dongmak seashore on Gangwha Island, Republic of Korea and its taxonomic position was determined through a polyphasic investigation. The bacterium was strictly aerobic, chemoheterotrophic, catalase- and oxidase-positive, consisted of non-motile rods and grew optimally at 30 °C, pH 7 and 1 % NaCl. The predominant cellular fatty acids were C18 : 1ω7c and cyclo-C19 : 0ω8c. The major isoprenoid quinone was Q-10. The major polar lipids were phosphatidylglycerol, a phosphoglycolipid and an aminolipid. Comparative 16S rRNA gene sequence analysis revealed that the isolate was closely related to members of the genus Maribius. The highest 16S rRNA gene sequence similarity was found to be 97.5 % to Maribius salinus followed by 97.4 % to Maribius pelagius; levels of 16S rRNA gene sequence similarity between the novel strain and other representatives of family Rhodobacteraceae were <95.5 %. The DNA G+C content was 66.7 mol % and DNA-DNA relatedness values with the type strains of species of the genus Maribius were 33-39 %. Based on combined data from a polyphasic investigation, strain GH1-23T (=KCTC 52957T=DSM 104950T) represents a novel species of the genus Maribius, for which the name Maribius pontilimi sp. nov. is proposed.}, } @article {pmid29205136, year = {2018}, author = {Wiese, J and Saha, M and Wenzel-Storjohann, A and Weinberger, F and Schmaljohann, R and Imhoff, JF}, title = {Vicingus serpentipes gen. nov., sp. nov., a new member of the Flavobacteriales from the North Sea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {333-340}, doi = {10.1099/ijsem.0.002509}, pmid = {29205136}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; North Sea ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; *Water Microbiology ; }, abstract = {A new member of the Flavobacteriales was isolated from the surface of a stone collected on the German North Sea shore. The bacterium, strain ANORD5T, is a mesophilic, chemoheterotrophic aerobic, typical marine bacterium. Optimal growth was observed at 20-30 °C, pH 7.0-8.5 and 1-2 % sea salt. The 16S rRNA gene sequence revealed a distant relationship with the representatives of the Cryomorphaceae, with less than 90 % sequence similarity. Strain ANORD5T forms a cluster together with Owenweeksia hongkongensis UST20020801T (89.9 %), Cryomorpha ignava 1-22T (87.9 %), Luteibaculum oceani CC-AMWY-103BT (88.1 %) and Phaeocystidibacter luteus PG2S01T (87.3 %). Strain ANORD5T has a low DNA G+C content (31 mol%). Based on morphological, physiological and phylogenetic data, strain ANORD5T is considered a type strain of a new species and a new genus of the family Cryomorphaceae for which the name Vicingus serpentipes is proposed. The type strain is ANORD5T (=NCIMB 15042T=DSM 103558T=MTCC 12686T).}, } @article {pmid29205133, year = {2018}, author = {Osman, G and Gao, Y and Wang, N and Mahmud, O and Sun, J and Zhang, T and Zhan, F and Zhang, Z and Lou, K}, title = {Pontibacter brevis sp. nov., isolated from rhizosphere soil of Tamarix ramosissima.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {81-86}, doi = {10.1099/ijsem.0.002455}, pmid = {29205133}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Tamaricaceae/*microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, oval-shaped and light pink pigmented bacterium, designated XAAS-2T, was isolated from rhizosphere soil of Tamarix ramosissima. The sole respiratory quinone of the type strain XAAS-2T was MK-7, and the principal cellular fatty acids were summed feature 4 (iso-C17 : 1 I and/or anteiso-C17 : 1 B) and iso-C15 : 0. The major polar lipids were phosphatidylethanolamine and two unidentified lipids. 16S rRNA gene sequence analysis indicated that strain XAAS-2T belonged to the genus Pontibacter within the family Cytophagaceae with sequence similarities of 93.9-97.1 % to other type species of the genus Pontibacter and to Pontibacter xinjiangensis CCTCC AB 207200T as the closest neighbour. The DNA G+C content of strain XAAS-2T was 50.6 mol%. The level of DNA-DNA relatedness of XAAS-2T and P. xinjiangensis CCTCC AB 207200T was 47.5 % (sd=3.27). Phenotypic and genotypic data suggested that strain XAAS-2T represents a novel species of the genus Pontibacter, for which the name Pontibacterbrevis sp. nov. is proposed, with the type strain XAAS-2T (=CCTCC AB 2016135T=JCM 31443T).}, } @article {pmid29205132, year = {2018}, author = {Kristyanto, S and Chaudhary, DK and Kim, J}, title = {Stakelama algicida sp. nov., novel algicidal species of the family Sphingomonadaceae isolated from seawater.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {317-323}, doi = {10.1099/ijsem.0.002506}, pmid = {29205132}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Sphingomonadaceae/*classification/genetics/isolation & purification ; Ubiquinone/chemistry ; *Water Microbiology ; }, abstract = {We conducted a taxonomic study of two algicidal bacteria, designated strains Yeonmyeong 1-13T and Yeonmyeong 1-11, isolated from seawater off Geoje Island in the South Sea, Republic of Korea. The two novel strains were yellow-pigmented, halotolerant, Gram-stain-negative, strictly aerobic, non-spore-forming, rod-shaped bacteria. Both strains were able to grow at 5-39 °C, pH 5.0-10.0 and 0-11 % (w/v) NaCl concentration. Based on the 16S rRNA gene sequence analysis, strains Yeonmyeong 1-13T and Yeonmyeong 1-11 belonged to the genus Stakelama and are closely related to Stakelama pacifica JLT832T (98.37% and 98.22 % sequence similarity, respectively). The pairwise sequence similarity between strains Yeonmyeong 1-13T and Yeonmyeong 1-11 was observed to be 99.50 %. In both strains, the only respiratory quinone was ubiquinone-10; the major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine and sphingoglycolipid; the major fatty acids were C18 : 1ω7c, C16 : 0 and C14 : 0 2-OH. DNA G+C content values of strains Yeonmyeong 1-13T and Yeonmyeong 1-11 were 65.1% and 64.9 mol%, respectively. The DNA-DNA relatedness between Yeonmyeong 1-13T and S. pacifica DSM 25059T was 28.7 %, which falls below the threshold value of 70 % for the strain to be considered as novel. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished strain Yeonmyeong 1-13T from its closest phylogenetic neighbours. Thus, strains Yeonmyeong 1-13T and Yeonmyeong 1-11 represent a novel species of the genus Stakelama, for which the name Stakelama algicida sp. nov. is proposed. The type strain is Yeonmyeong 1-13T (=KEMB 9005-324T=JCM 31498T).}, } @article {pmid29205131, year = {2018}, author = {Li, AZ and Han, XB and Lin, LZ and Zhang, MX and Zhu, HH}, title = {Gramella antarctica sp. nov., isolated from marine surface sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {358-363}, doi = {10.1099/ijsem.0.002513}, pmid = {29205131}, issn = {1466-5034}, mesh = {Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, yellow-coloured, motile by gliding, rod-shaped bacterial strain, designated R17H11T, was isolated from surface sediment collected from the Ross Sea, Antarctica. Growth optimally occurred at 25-30 °C, at pH 7.0-7.5 and in the presence of 3 % NaCl (w/v). Phylogenetic trees based on 16S rRNA gene sequences indicated that strain R17H11T clustered together with Gramella flava JLT2011T and fell within the genus Gramella. Strain R17H11T shared the highest 16S rRNA gene similarities (96.1 and 96.0 %) with the type strains of Gramella forsetii and G. flava, and 92.6-95.5 % similarities with those of other known Gramella species. Strain R17H11T contained menaquinone-6 as the only isoprenoid quinone. The major fatty acids (>5 %) were summed feature 3 (17.5 %, comprising C16 : 1ω7c and/or C16 : 1ω6c), iso-C15 : 0 (14.0 %), summed feature 9 (11.8 %, comprising 10-methyl C16 : 0 and/or iso-C17 : 1ω9c), iso-C17 : 0 3-OH (11.8 %), iso-C16 : 0 (7.4 %), C17 : 1ω6c (6.9 %) and anteiso-C15 : 0 (5.1 %). The major polar lipids were phosphatidylethanolamine, four unidentified lipids, an unidentified aminolipid, an unidentified aminophospholipid and an unidentified glycolipid. The DNA G+C content of strain R17H11T was 38.6 mol%. On the basis of the phylogenetic, physiological and chemotaxonomic characteristics, strain R17H11T represents a novel species in the genus Gramella, for which the name Gramellaantarctica sp. nov. is proposed. The type strain of the novel species is R17H11T (=GDMCC 1.1208T=KCTC 52925T).}, } @article {pmid29205128, year = {2018}, author = {Li, AZ and Lin, LZ and Zhang, MX and Zhu, HH}, title = {Antarcticibacterium flavum gen. nov., sp. nov., isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {254-259}, doi = {10.1099/ijsem.0.002489}, pmid = {29205128}, issn = {1466-5034}, mesh = {Antarctic Regions ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacteriaceae/*classification/genetics/isolation & purification ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, strictly aerobic, yellow-pigmented, non-gliding, oval to rod-shaped bacterial strain, designated JB01H24T, belonging to the family Flavobacteriaceae, was isolated from marine surface sediment collected from the Ross Sea, Antarctica. Strain JB01H24T grew at 4-40 °C (optimum 25-30 °C), pH 7.0-9.0 (optimum 7.5-8.0), and in the presence of 0-8 % NaCl (optimum 3 %, w/v). Phylogenetic analysis based on 16S rRNA gene sequences showed that strain JB01H24T formed an independent linkage within the family Flavobacteriaceae and was closely related with the genus Gillisia. Strain JB01H24T exhibited 16S rRNA gene sequence similarities of 95.3-91.5 % and 94.9-94.0 % to the type strains of the genera Gillisia and Salinimicrobium, respectively. The major fatty acids (>5 %) were iso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c), anteiso-C15 : 0, iso-C15 : 1 G and summed feature 9 (iso-C17 : 1ω9c and/or 10-methyl C16 : 0). The major polar lipids were phosphatidylethanolamine, seven unidentified lipids, two unidentified aminolipids and an unidentified aminophospholipid. Strain JB01H24T contained menaquinone-6 as the only ubiquinone. The DNA G+C content was 42.4 mol%. On the basis of phylogenetic, physiological and chemotaxonomic properties, strain JB01H24T is considered to represent a novel species of a new genus within the family Flavobacteriaceae, for which the name Antarcticibacterium flavum gen. nov., sp. nov. is proposed. The type strain of Antarcticibacterium flavum is JB01H24T (=GDMCC 1.1229T=KCTC 52984T).}, } @article {pmid29205127, year = {2018}, author = {Riojas, MA and McGough, KJ and Rider-Riojas, CJ and Rastogi, N and Hazbón, MH}, title = {Phylogenomic analysis of the species of the Mycobacterium tuberculosis complex demonstrates that Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and Mycobacterium pinnipedii are later heterotypic synonyms of Mycobacterium tuberculosis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {324-332}, doi = {10.1099/ijsem.0.002507}, pmid = {29205127}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques/methods ; DNA, Bacterial/genetics ; Mycobacterium tuberculosis/*classification ; Nucleic Acid Hybridization ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The species within the Mycobacterium tuberculosis Complex (MTBC) have undergone numerous taxonomic and nomenclatural changes, leaving the true structure of the MTBC in doubt. We used next-generation sequencing (NGS), digital DNA-DNA hybridization (dDDH), and average nucleotide identity (ANI) to investigate the relationship between these species. The type strains of Mycobacterium africanum, Mycobacterium bovis, Mycobacterium caprae, Mycobacterium microti and Mycobacterium pinnipedii were sequenced via NGS. Pairwise dDDH and ANI comparisons between these, previously sequenced MTBC type strain genomes (including 'Mycobacterium canettii', 'Mycobacterium mungi' and 'Mycobacterium orygis') and M. tuberculosis H37RvT were performed. Further, all available genome sequences in GenBank for species in or putatively in the MTBC were compared to H37RvT. Pairwise results indicated that all of the type strains of the species are extremely closely related to each other (dDDH: 91.2-99.2 %, ANI: 99.21-99.92 %), greatly exceeding the respective species delineation thresholds, thus indicating that they belong to the same species. Results from the GenBank genomes indicate that all the strains examined are within the circumscription of H37RvT (dDDH: 83.5-100 %). We, therefore, formally propose a union of the species of the MTBC as M. tuberculosis. M. africanum, M. bovis, M. caprae, M. microti and M. pinnipedii are reclassified as later heterotypic synonyms of M. tuberculosis. 'M. canettii', 'M. mungi', and 'M. orygis' are classified as strains of the species M. tuberculosis. We further recommend use of the infrasubspecific term 'variant' ('var.') and infrasubspecific designations that generally retain the historical nomenclature associated with the groups or otherwise convey such characteristics, e.g. M. tuberculosis var. bovis.}, } @article {pmid29205126, year = {2018}, author = {Passet, V and Brisse, S}, title = {Description of Klebsiella grimontii sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {377-381}, doi = {10.1099/ijsem.0.002517}, pmid = {29205126}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Humans ; Klebsiella/*classification/genetics ; Klebsiella Infections/microbiology ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Strains previously identified as Klebsiella oxytocaphylogroup Ko6 were characterized by rpoB, gyrA and rrs gene sequencing, genome-sequence based average nucleotide identity analysis and their biochemical characteristics. rpoB and gyrA sequencing demonstrated that the Ko6 strains formed a well-demarcated sequence cluster related to, but distinct from, Klebsiella oxytoca (which includes strains previously labelled as K. oxytocaphylogroup Ko2) and Klebsiella michiganensis (Ko1). The average nucleotide identity values of Ko6 with K. oxytoca and K. michiganensis were 91.2 and 93.47 %, respectively. The inability to metabolize melezitose differentiated most of the Ko6 strains from K. oxytoca and K. michiganensis. Based on its genetic and phenotypic characteristics, we propose the name Klebsiella grimontii for the Ko6 sequence cluster, with strain 06D021T (=CIP111401T, DSM 105630T) as the type strain. Strains of Klebsiella grimontii were isolated from human blood cultures, wound infections, antibiotic-associated haemorrhagic colitis and faecal carriage.}, } @article {pmid29205125, year = {2018}, author = {Chaudhary, DK and Kim, J}, title = {Sphingopyxis nepalensis sp. nov., isolated from oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {364-370}, doi = {10.1099/ijsem.0.002514}, pmid = {29205125}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nepal ; Nucleic Acid Hybridization ; *Petroleum Pollution ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Soil ; *Soil Microbiology ; Spermidine/chemistry ; Sphingomonadaceae/*classification/genetics/isolation & purification ; Ubiquinone/chemistry ; }, abstract = {During a study of oil-degrading bacteria, three yellow-coloured, Gram-stain-negative, non-motile and rod-shaped bacteria, designated strains Ktm-14T, Ktm-17 and Ktm-18, were isolated from oil-contaminated soil of Biratnagar, Morang, Nepal. The strains were able to grow at 15-37 °C, pH 4.5-10.0 and 0-2 % (w/v) NaCl concentration. Strains Ktm-14T, Ktm-17 and Ktm-18 were characterized by multiple taxonomic approaches. Based on 16S rRNA gene sequence analysis, strains Ktm-14T, Ktm-17 and Ktm-18 belonged to the genus Sphingopyxis and shared highest sequence similarity with Sphingopyxis ginsengisoliGsoil 250T (98.94 %). The only respiratory quinone was ubiquinone-10 and the predominant polyamine was spermidine. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol, diphosphatidylglycerol, phosphatidylcholine, phosphatidylmonomethylethanolamine and sphingoglycolipids. The predominant fatty acids were C17 : 1ω6c, summed feature 8 (C18 : 1ω7c and/or C18 : 1ω6c), summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c) and C16 : 0. The DNA G+C content values of strains Ktm-14T, Ktm-17 and Ktm-18 were 65.8, 65.9 and 65.6 mol%, respectively. The DNA-DNA relatedness between Ktm-14T and Ktm-17 and Ktm-18 were higher than 70 % but with closely related reference strains were less than 40 %. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished strain Ktm-14T from its closest phylogenetic neighbours. Thus, strain Ktm-14T represents a novel species of the genus Sphingopyxis, for which the name Sphingopyxisnepalensis sp. nov. is proposed. The type strain is Ktm-14T (=KEMB 9005-694T=KACC 19389T=JCM 32250T), and strains Ktm-17 and Ktm-18 represent two additional strains.}, } @article {pmid29203925, year = {2018}, author = {Brosi, BJ and Delaplane, KS and Boots, M and Roode, JC}, title = {Publisher Correction: Ecological and evolutionary approaches to managing honeybee disease.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {196}, doi = {10.1038/s41559-017-0394-1}, pmid = {29203925}, issn = {2397-334X}, abstract = {In the HTML version of this Review originally published, a technical error led to the images in Box 2 being swapped over. This was corrected on 28 August 2017.}, } @article {pmid29203924, year = {2018}, author = {Luo, YJ and Kanda, M and Koyanagi, R and Hisata, K and Akiyama, T and Sakamoto, H and Sakamoto, T and Satoh, N}, title = {Nemertean and phoronid genomes reveal lophotrochozoan evolution and the origin of bilaterian heads.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {141-151}, doi = {10.1038/s41559-017-0389-y}, pmid = {29203924}, issn = {2397-334X}, mesh = {Animals ; *Biological Evolution ; Evolution, Molecular ; *Genome ; Head/anatomy & histology ; Invertebrates/*anatomy & histology/*genetics ; Phylogeny ; }, abstract = {Nemerteans (ribbon worms) and phoronids (horseshoe worms) are closely related lophotrochozoans-a group of animals including leeches, snails and other invertebrates. Lophotrochozoans represent a superphylum that is crucial to our understanding of bilaterian evolution. However, given the inconsistency of molecular and morphological data for these groups, their origins have been unclear. Here, we present draft genomes of the nemertean Notospermus geniculatus and the phoronid Phoronis australis, together with transcriptomes along the adult bodies. Our genome-based phylogenetic analyses place Nemertea sister to the group containing Phoronida and Brachiopoda. We show that lophotrochozoans share many gene families with deuterostomes, suggesting that these two groups retain a core bilaterian gene repertoire that ecdysozoans (for example, flies and nematodes) and platyzoans (for example, flatworms and rotifers) do not. Comparative transcriptomics demonstrates that lophophores of phoronids and brachiopods are similar not only morphologically, but also at the molecular level. Despite dissimilar head structures, lophophores express vertebrate head and neuronal marker genes. This finding suggests a common origin of bilaterian head patterning, although different heads evolved independently in each lineage. Furthermore, we observe lineage-specific expansions of innate immunity and toxin-related genes. Together, our study reveals a dual nature of lophotrochozoans, where conserved and lineage-specific features shape their evolution.}, } @article {pmid29203923, year = {2018}, author = {Mullon, C and Keller, L and Lehmann, L}, title = {Social polymorphism is favoured by the co-evolution of dispersal with social behaviour.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {132-140}, doi = {10.1038/s41559-017-0397-y}, pmid = {29203923}, issn = {2397-334X}, mesh = {*Animal Distribution ; Animals ; Biological Evolution ; Models, Genetic ; *Polymorphism, Genetic ; *Social Behavior ; }, abstract = {Dispersal determines gene flow among groups in a population and so plays a major role in many ecological and evolutionary processes. As gene flow shapes kin structure, dispersal is important to the evolution of social behaviours that influence reproduction within groups. Conversely, dispersal depends on kin structure and social behaviour. Dispersal and social behaviour therefore co-evolve, but the nature and consequences of this interplay are not well understood. Here, we show that it readily leads to the emergence of two social morphs: a sessile, benevolent morph expressed by individuals who tend to increase the reproduction of others within their group relative to their own; and a dispersive, self-serving morph expressed by individuals who tend to increase their own reproduction. This social polymorphism arises due to a positive linkage between the loci responsible for dispersal and social behaviour, leading to benevolent individuals preferentially interacting with relatives and self-serving individuals with non-relatives. We find that this linkage is favoured under a large spectrum of conditions, suggesting that associations between dispersal and other social traits should be common in nature. In line with this prediction, dispersers across a wide range of organisms have been reported to differ in their social tendencies from non-dispersers.}, } @article {pmid29203922, year = {2018}, author = {Hautier, Y and Isbell, F and Borer, ET and Seabloom, EW and Harpole, WS and Lind, EM and MacDougall, AS and Stevens, CJ and Adler, PB and Alberti, J and Bakker, JD and Brudvig, LA and Buckley, YM and Cadotte, M and Caldeira, MC and Chaneton, EJ and Chu, C and Daleo, P and Dickman, CR and Dwyer, JM and Eskelinen, A and Fay, PA and Firn, J and Hagenah, N and Hillebrand, H and Iribarne, O and Kirkman, KP and Knops, JMH and La Pierre, KJ and McCulley, RL and Morgan, JW and Pärtel, M and Pascual, J and Price, JN and Prober, SM and Risch, AC and Sankaran, M and Schuetz, M and Standish, RJ and Virtanen, R and Wardle, GM and Yahdjian, L and Hector, A}, title = {Local loss and spatial homogenization of plant diversity reduce ecosystem multifunctionality.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {50-56}, doi = {10.1038/s41559-017-0395-0}, pmid = {29203922}, issn = {2397-334X}, mesh = {*Biodiversity ; *Grassland ; Models, Biological ; *Plants ; Spatial Analysis ; }, abstract = {Biodiversity is declining in many local communities while also becoming increasingly homogenized across space. Experiments show that local plant species loss reduces ecosystem functioning and services, but the role of spatial homogenization of community composition and the potential interaction between diversity at different scales in maintaining ecosystem functioning remains unclear, especially when many functions are considered (ecosystem multifunctionality). We present an analysis of eight ecosystem functions measured in 65 grasslands worldwide. We find that more diverse grasslands-those with both species-rich local communities (α-diversity) and large compositional differences among localities (β-diversity)-had higher levels of multifunctionality. Moreover, α- and β-diversity synergistically affected multifunctionality, with higher levels of diversity at one scale amplifying the contribution to ecological functions at the other scale. The identity of species influencing ecosystem functioning differed among functions and across local communities, explaining why more diverse grasslands maintained greater functionality when more functions and localities were considered. These results were robust to variation in environmental drivers. Our findings reveal that plant diversity, at both local and landscape scales, contributes to the maintenance of multiple ecosystem services provided by grasslands. Preserving ecosystem functioning therefore requires conservation of biodiversity both within and among ecological communities.}, } @article {pmid29203921, year = {2018}, author = {Des Roches, S and Post, DM and Turley, NE and Bailey, JK and Hendry, AP and Kinnison, MT and Schweitzer, JA and Palkovacs, EP}, title = {The ecological importance of intraspecific variation.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {57-64}, doi = {10.1038/s41559-017-0402-5}, pmid = {29203921}, issn = {2397-334X}, mesh = {*Biodiversity ; *Biomass ; Ecosystem ; *Genetic Variation ; Models, Biological ; Species Specificity ; }, abstract = {Human activity is causing wild populations to experience rapid trait change and local extirpation. The resulting effects on intraspecific variation could have substantial consequences for ecological processes and ecosystem services. Although researchers have long acknowledged that variation among species influences the surrounding environment, only recently has evidence accumulated for the ecological importance of variation within species. We conducted a meta-analysis comparing the ecological effects of variation within a species (intraspecific effects) with the effects of replacement or removal of that species (species effects). We evaluated direct and indirect ecological responses, including changes in abundance (or biomass), rates of ecological processes and changes in community composition. Our results show that intraspecific effects are often comparable to, and sometimes stronger than, species effects. Species effects tend to be larger for direct ecological responses (for example, through consumption), whereas intraspecific effects and species effects tend to be similar for indirect responses (for example, through trophic cascades). Intraspecific effects are especially strong when indirect interactions alter community composition. Our results summarize data from the first generation of studies examining the relative ecological effects of intraspecific variation. Our conclusions can help inform the design of future experiments and the formulation of strategies to quantify and conserve biodiversity.}, } @article {pmid29203920, year = {2018}, author = {Lewis, SH and Quarles, KA and Yang, Y and Tanguy, M and Frézal, L and Smith, SA and Sharma, PP and Cordaux, R and Gilbert, C and Giraud, I and Collins, DH and Zamore, PD and Miska, EA and Sarkies, P and Jiggins, FM}, title = {Pan-arthropod analysis reveals somatic piRNAs as an ancestral defence against transposable elements.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {174-181}, pmid = {29203920}, issn = {2397-334X}, support = {R01 GM062862/GM/NIGMS NIH HHS/United States ; 281668//European Research Council/International ; //Wellcome Trust/United Kingdom ; MC_UP_1102/13//Medical Research Council/United Kingdom ; R37 GM062862/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Arthropods/*genetics ; DNA Transposable Elements/*physiology ; *Evolution, Molecular ; RNA, Messenger/*physiology ; RNA, Small Interfering/*genetics/metabolism ; }, abstract = {In animals, small RNA molecules termed PIWI-interacting RNAs (piRNAs) silence transposable elements (TEs), protecting the germline from genomic instability and mutation. piRNAs have been detected in the soma in a few animals, but these are believed to be specific adaptations of individual species. Here, we report that somatic piRNAs were probably present in the ancestral arthropod more than 500 million years ago. Analysis of 20 species across the arthropod phylum suggests that somatic piRNAs targeting TEs and messenger RNAs are common among arthropods. The presence of an RNA-dependent RNA polymerase in chelicerates (horseshoe crabs, spiders and scorpions) suggests that arthropods originally used a plant-like RNA interference mechanism to silence TEs. Our results call into question the view that the ancestral role of the piRNA pathway was to protect the germline and demonstrate that small RNA silencing pathways have been repurposed for both somatic and germline functions throughout arthropod evolution.}, } @article {pmid29203919, year = {2018}, author = {Atwater, DZ and Ervine, C and Barney, JN}, title = {Climatic niche shifts are common in introduced plants.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {34-43}, doi = {10.1038/s41559-017-0396-z}, pmid = {29203919}, issn = {2397-334X}, mesh = {*Ecosystem ; *Introduced Species ; *Plant Dispersal ; Species Specificity ; }, abstract = {Our understanding of how climate influences species distributions and our ability to assess the risk of introduced species depend on the assumption that species' climatic niches remain stable across space and time. While niche shifts have been detected in individual invasive species, one assessment of ~50 plants in Europe and North America concluded that niche shifts were rare, while another concluded the opposite. These contradictory findings, limited in species number and geographic scope, leave open a need to understand how often introduced species experience niche shifts and whether niche shifts can be predicted. We found evidence of climatic niche shifts in 65-100% of 815 terrestrial plant species introduced across five continents, depending on how niche shifts were measured. Individual species responses were idiosyncratic, but we generally saw that niche shifts reflected changes in climate availability at the continent scale and were largest in long-lived and cultivated species. Smaller intercontinental niche shifts occurred within species' native ranges. Overall, the climatic niches of terrestrial plant species were not conserved as they crossed continents. These results have major consequences for applying environmental niche models to assess the risk of invasive species and for predicting species responses to climate change. Our findings challenge the tenet that species' niches are conserved aspects of their ecology.}, } @article {pmid29203918, year = {2018}, author = {Firbank, LG}, title = {The beef with sustainability.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {5-6}, doi = {10.1038/s41559-017-0422-1}, pmid = {29203918}, issn = {2397-334X}, } @article {pmid29203917, year = {2018}, author = {Rizzuto, M and Carbone, C and Pawar, S}, title = {Foraging constraints reverse the scaling of activity time in carnivores.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {247-253}, doi = {10.1038/s41559-017-0386-1}, pmid = {29203917}, issn = {2397-334X}, abstract = {The proportion of time an animal spends actively foraging in a day determines its long-term fitness. Here, we derive a general mathematical model for the scaling of this activity time with body size in consumers. We show that this scaling can change from positive (increasing with size) to negative (decreasing with size) if the detectability and availability of preferred prey sizes is a limiting factor. These predictions are supported by a global dataset on 73 terrestrial carnivore species from 8 families spanning >3 orders of magnitude in size. Carnivores weighing ∼5 kg experience high foraging costs because their diets include significant proportions of relatively small (invertebrate) prey. As a result, they show an increase in activity time with size. This shifts to a negative scaling in larger carnivores as they shift to foraging on less costly vertebrate prey. Our model can be generalized to other classes of terrestrial and aquatic consumers and offers a general framework for mechanistically linking body size to population fitness and vulnerability in consumers.}, } @article {pmid29203916, year = {2018}, author = {Eshel, G and Shepon, A and Shaket, T and Cotler, BD and Gilutz, S and Giddings, D and Raymo, ME and Milo, R}, title = {A model for 'sustainable' US beef production.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {81-85}, doi = {10.1038/s41559-017-0390-5}, pmid = {29203916}, issn = {2397-334X}, mesh = {Animal Husbandry/*methods ; Animals ; *Cattle ; Conservation of Natural Resources ; Grassland ; Humans ; Meat/*analysis ; *Nutritive Value ; Terminology as Topic ; United States ; }, abstract = {Food production dominates land, water and fertilizer use and is a greenhouse gas source. In the United States, beef production is the main agricultural resource user overall, as well as per kcal or g of protein. Here, we offer a possible, non-unique, definition of 'sustainable' beef as that subsisting exclusively on grass and by-products, and quantify its expected US production as a function of pastureland use. Assuming today's pastureland characteristics, all of the pastureland that US beef currently use can sustainably deliver ≈45% of current production. Rewilding this pastureland's less productive half (≈135 million ha) can still deliver ≈43% of current beef production. In all considered scenarios, the ≈32 million ha of high-quality cropland that beef currently use are reallocated for plant-based food production. These plant items deliver 2- to 20-fold more calories and protein than the replaced beef and increase the delivery of protective nutrients, but deliver no B12. Increased deployment of rapid rotational grazing or grassland multi-purposing may increase beef production capacity.}, } @article {pmid29203910, year = {2018}, author = {Verma, N and Pan, H and Doré, LC and Shukla, A and Li, QV and Pelham-Webb, B and Teijeiro, V and González, F and Krivtsov, A and Chang, CJ and Papapetrou, EP and He, C and Elemento, O and Huangfu, D}, title = {TET proteins safeguard bivalent promoters from de novo methylation in human embryonic stem cells.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {83-95}, pmid = {29203910}, issn = {1546-1718}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; R01 CA194547/CA/NCI NIH HHS/United States ; R01 DK096239/DK/NIDDK NIH HHS/United States ; }, abstract = {TET enzymes oxidize 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC), which can lead to DNA demethylation. However, direct connections between TET-mediated DNA demethylation and transcriptional output are difficult to establish owing to challenges in distinguishing global versus locus-specific effects. Here we show that TET1, TET2 and TET3 triple-knockout (TKO) human embryonic stem cells (hESCs) exhibit prominent bivalent promoter hypermethylation without an overall corresponding decrease in gene expression in the undifferentiated state. Focusing on the bivalent PAX6 locus, we find that increased DNMT3B binding is associated with promoter hypermethylation, which precipitates a neural differentiation defect and failure of PAX6 induction during differentiation. dCas9-mediated locus-specific demethylation and global inactivation of DNMT3B in TKO hESCs partially reverses the hypermethylation at the PAX6 promoter and improves differentiation to neuroectoderm. Taking these findings together with further genome-wide methylation and TET1 and DNMT3B ChIP-seq analyses, we conclude that TET proteins safeguard bivalent promoters from de novo methylation to ensure robust lineage-specific transcription upon differentiation.}, } @article {pmid29203909, year = {2018}, author = {Zhang, Y and Xiang, Y and Yin, Q and Du, Z and Peng, X and Wang, Q and Fidalgo, M and Xia, W and Li, Y and Zhao, ZA and Zhang, W and Ma, J and Xu, F and Wang, J and Li, L and Xie, W}, title = {Dynamic epigenomic landscapes during early lineage specification in mouse embryos.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {96-105}, doi = {10.1038/s41588-017-0003-x}, pmid = {29203909}, issn = {1546-1718}, abstract = {In mammals, all somatic development originates from lineage segregation in early embryos. However, the dynamics of transcriptomes and epigenomes acting in concert with initial cell fate commitment remains poorly characterized. Here we report a comprehensive investigation of transcriptomes and base-resolution methylomes for early lineages in peri- and postimplantation mouse embryos. We found allele-specific and lineage-specific de novo methylation at CG and CH sites that led to differential methylation between embryonic and extraembryonic lineages at promoters of lineage regulators, gene bodies, and DNA-methylation valleys. By using Hi-C experiments to define chromatin architecture across the same developmental period, we demonstrated that both global demethylation and remethylation in early development correlate with chromatin compartments. Dynamic local methylation was evident during gastrulation, which enabled the identification of putative regulatory elements. Finally, we found that de novo methylation patterning does not strictly require implantation. These data reveal dynamic transcriptomes, DNA methylomes, and 3D chromatin landscapes during the earliest stages of mammalian lineage specification.}, } @article {pmid29203882, year = {2018}, author = {Zucchini, L and Mercy, C and Garcia, PS and Cluzel, C and Gueguen-Chaignon, V and Galisson, F and Freton, C and Guiral, S and Brochier-Armanet, C and Gouet, P and Grangeasse, C}, title = {PASTA repeats of the protein kinase StkP interconnect cell constriction and separation of Streptococcus pneumoniae.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {197-209}, doi = {10.1038/s41564-017-0069-3}, pmid = {29203882}, issn = {2058-5276}, abstract = {Eukaryotic-like serine/threonine kinases (eSTKs) with extracellular PASTA repeats are key membrane regulators of bacterial cell division. How PASTA repeats govern eSTK activation and function remains elusive. Using evolution- and structural-guided approaches combined with cell imaging, we disentangle the role of each PASTA repeat of the eSTK StkP from Streptococcus pneumoniae. While the three membrane-proximal PASTA repeats behave as interchangeable modules required for the activation of StkP independently of cell wall binding, they also control the septal cell wall thickness. In contrast, the fourth and membrane-distal PASTA repeat directs StkP localization at the division septum and encompasses a specific motif that is critical for final cell separation through interaction with the cell wall hydrolase LytB. We propose a model in which the extracellular four-PASTA domain of StkP plays a dual function in interconnecting the phosphorylation of StkP endogenous targets along with septal cell wall remodelling to allow cell division of the pneumococcus.}, } @article {pmid29203881, year = {2018}, author = {Yang, YA and Lee, S and Zhao, J and Thompson, AJ and McBride, R and Tsogtbaatar, B and Paulson, JC and Nussinov, R and Deng, L and Song, J}, title = {In vivo tropism of Salmonella Typhi toxin to cells expressing a multiantennal glycan receptor.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {155-163}, pmid = {29203881}, issn = {2058-5276}, support = {HHSN261200800001C/RC/CCR NIH HHS/United States ; HHSN261200800001E/CA/NCI NIH HHS/United States ; R01 AI114730/AI/NIAID NIH HHS/United States ; }, abstract = {Typhoid fever is a life-threatening disease, but little is known about the molecular bases for its unique clinical presentation. Typhoid toxin, a unique virulence factor of Salmonella Typhi (the cause of typhoid fever), recapitulates in an animal model many symptoms of typhoid fever. Typhoid toxin binding to its glycan receptor Neu5Ac is central, but, due to the ubiquity of Neu5Ac, how typhoid toxin causes specific symptoms remains elusive. Here we show that typhoid toxin displays in vivo tropism to cells expressing multiantennal glycoprotein receptors, particularly on endothelial cells of arterioles in the brain and immune cells, which is in line with typhoid symptoms. Neu5Ac displayed by multiantennal N-glycans, rather than a single Neu5Ac, appears to serve as the high-affinity receptor, as typhoid toxin possesses five identical binding pockets per toxin. Human counterparts also express the multiantennal Neu5Ac receptor. Here we also show that mice immunized with inactive typhoid toxins and challenged with wild-type typhoid toxin presented neither the characteristic in vivo tropism nor symptoms. These mice were protected against a lethal-dose toxin challenge, but Ty21a-vaccinated mice were not. Cumulatively, these results reveal remarkable features describing how a bacterial exotoxin induces virulence exclusively in specific cells at the organismal level.}, } @article {pmid29203721, year = {2018}, author = {Lello, J and Fenton, A}, title = {Correction to 'Lost in transmission…?'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, doi = {10.1098/rstb.2017.0358}, pmid = {29203721}, issn = {1471-2970}, } @article {pmid29203720, year = {2018}, author = {Cavalier-Smith, T}, title = {Vendozoa and selective forces on animal origin and early diversification: reply to Dufour and McIlroy (2017).}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203720}, issn = {1471-2970}, } @article {pmid29203719, year = {2018}, author = {Dufour, SC and McIlroy, D}, title = {An Ediacaran pre-placozoan alternative to the pre-sponge route towards the Cambrian explosion of animal life: a comment on Cavalier-Smith 2017.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203719}, issn = {1471-2970}, } @article {pmid29203718, year = {2018}, author = {Zarouchlioti, C and Parfitt, DA and Li, W and Gittings, LM and Cheetham, ME}, title = {DNAJ Proteins in neurodegeneration: essential and protective factors.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203718}, issn = {1471-2970}, support = {CHEETHAM/OCT15/881-792//Motor Neurone Disease Association/United Kingdom ; MR/N004434/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Fetal Proteins/*genetics/metabolism ; HSP40 Heat-Shock Proteins/*genetics/metabolism ; Humans ; Mice ; Molecular Chaperones/*genetics/metabolism ; Neurodegenerative Diseases/*genetics ; Protein Folding ; Rats ; }, abstract = {Maintenance of protein homeostasis is vitally important in post-mitotic cells, particularly neurons. Neurodegenerative diseases such as polyglutamine expansion disorders-like Huntington's disease or spinocerebellar ataxia (SCA), Alzheimer's disease, fronto-temporal dementia (FTD), amyotrophic lateral sclerosis (ALS) and Parkinson's disease-are often characterized by the presence of inclusions of aggregated protein. Neurons contain complex protein networks dedicated to protein quality control and maintaining protein homeostasis, or proteostasis. Molecular chaperones are a class of proteins with prominent roles in maintaining proteostasis, which act to bind and shield hydrophobic regions of nascent or misfolded proteins while allowing correct folding, conformational changes and enabling quality control. There are many different families of molecular chaperones with multiple functions in proteostasis. The DNAJ family of molecular chaperones is the largest chaperone family and is defined by the J-domain, which regulates the function of HSP70 chaperones. DNAJ proteins can also have multiple other protein domains such as ubiquitin-interacting motifs or clathrin-binding domains leading to diverse and specific roles in the cell, including targeting client proteins for degradation via the proteasome, chaperone-mediated autophagy and uncoating clathrin-coated vesicles. DNAJ proteins can also contain ER-signal peptides or mitochondrial leader sequences, targeting them to specific organelles in the cell. In this review, we discuss the multiple roles of DNAJ proteins and in particular focus on the role of DNAJ proteins in protecting against neurodegenerative diseases caused by misfolded proteins. We also discuss the role of DNAJ proteins as direct causes of inherited neurodegeneration via mutations in DNAJ family genes.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203717, year = {2018}, author = {Criado-Marrero, M and Rein, T and Binder, EB and Porter, JT and Koren, J and Blair, LJ}, title = {Hsp90 and FKBP51: complex regulators of psychiatric diseases.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203717}, issn = {1471-2970}, support = {G12 MD007579/MD/NIMHD NIH HHS/United States ; R01 MH103848/MH/NIMH NIH HHS/United States ; R15 MH101700/MH/NIMH NIH HHS/United States ; }, mesh = {Animals ; HSP90 Heat-Shock Proteins/*genetics/metabolism ; Humans ; Mental Disorders/*genetics ; Stress, Psychological/*genetics ; Tacrolimus Binding Proteins/*genetics/metabolism ; }, abstract = {Mood disorders affect nearly a quarter of the world's population. Therefore, understanding the molecular mechanisms underlying these conditions is of great importance. FK-506 binding protein 5 (FKBP5) encodes the FKBP51 protein, a heat shock protein 90 kDa (Hsp90) co-chaperone, and is a risk factor for several affective disorders. FKBP51, in coordination with Hsp90, regulates glucocorticoid receptor (GR) activity via a short negative feedback loop. This signalling pathway rapidly restores homeostasis in the hypothalamic-pituitary-adrenal (HPA) axis following stress. Expression of FKBP5 increases with age through reduced DNA methylation. High levels of FKBP51 are linked to GR resistance and reduced stress coping behaviour. Moreover, common allelic variants in the FKBP5 gene are associated with increased risk of developing affective disorders like anxiety, depression and post-traumatic stress disorder (PTSD). This review highlights the current understanding of the Hsp90 co-chaperone, FKBP5, in disease from both human and animal studies. In addition, FKBP5 genetic implications in the clinic involving life stress exposure, gender differences and treatment outcomes are discussed.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203716, year = {2018}, author = {van Eden, W}, title = {Immune tolerance therapies for autoimmune diseases based on heat shock protein T-cell epitopes.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203716}, issn = {1471-2970}, mesh = {Animals ; Autoimmune Diseases/*therapy ; Epitopes, T-Lymphocyte/*immunology ; Heat-Shock Proteins/*genetics/immunology ; Humans ; *Immune Tolerance ; Mice ; Rats ; T-Lymphocytes, Regulatory/*immunology ; }, abstract = {Experimental models of autoimmune diseases have revealed the disease protective role of heat shock proteins (HSPs). Both the administration of exogenous extracellular, mostly recombinant, HSP and the experimental co-induction of endogenous intracellular HSP in models have been shown to lead to production of disease protective regulatory T cells (Tregs). Similar to HSP taken up from extracellular bodily fluids, due to stress-related autophagy upregulated HSP also from intracellular sources is a major provider for the major histocompatibility class II (MHCII) ligandome; therefore, both extracellular and intracellular HSP can be prominent targets of Treg. The development of therapeutic peptide vaccines for the restoration of immune tolerance in inflammatory diseases is an area of intensive research. In this area, HSPs are a target for tolerance-inducing T-cell therapy, because of their wide expression in inflamed tissues. In humans, in whom the actual disease trigger is frequently unknown, HSP peptides offer chances for tolerance-promoting interventions through induction of HSP-specific Treg. Recently, we have shown the ability of a bacterial HSP70-derived peptide, HSP70-B29, to induce HSP-specific Tregs that suppressed arthritis by cross-recognition of their mammalian HSP70 homologues, abundantly present in the MHCII ligandome of stressed mouse and human antigen-presenting cells in inflamed tissues.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203715, year = {2018}, author = {Ranek, MJ and Stachowski, MJ and Kirk, JA and Willis, MS}, title = {The role of heat shock proteins and co-chaperones in heart failure.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203715}, issn = {1471-2970}, support = {14SDG20380148//American Heart Association-American Stroke Association/United States ; R01 HL104129/HL/NHLBI NIH HHS/United States ; R01 HL136737/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Heart Failure/*genetics/physiopathology ; Heat-Shock Proteins/*genetics/metabolism ; Humans ; Mice ; Molecular Chaperones/genetics/metabolism ; Myocytes, Cardiac/*metabolism ; Rats ; }, abstract = {The ongoing contractile and metabolic demands of the heart require a tight control over protein quality control, including the maintenance of protein folding, turnover and synthesis. In heart disease, increases in mechanical and oxidative stresses, post-translational modifications (e.g., phosphorylation), for example, decrease protein stability to favour misfolding in myocardial infarction, heart failure or ageing. These misfolded proteins are toxic to cardiomyocytes, directly contributing to the common accumulation found in human heart failure. One of the critical class of proteins involved in protecting the heart against these threats are molecular chaperones, including the heat shock protein70 (HSP70), HSP90 and co-chaperones CHIP (carboxy terminus of Hsp70-interacting protein, encoded by the Stub1 gene) and BAG-3 (BCL2-associated athanogene 3). Here, we review their emerging roles in the maintenance of cardiomyocytes in human and experimental models of heart failure, including their roles in facilitating the removal of misfolded and degraded proteins, inhibiting apoptosis and maintaining the structural integrity of the sarcomere and regulation of nuclear receptors. Furthermore, we discuss emerging evidence of increased expression of extracellular HSP70, HSP90 and BAG-3 in heart failure, with complementary independent roles from intracellular functions with important therapeutic and diagnostic considerations. While our understanding of these major HSPs in heart failure is incomplete, there is a clear potential role for therapeutic modulation of HSPs in heart failure with important contextual considerations to counteract the imbalance of protein damage and endogenous protein quality control systems.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203714, year = {2018}, author = {Archer, AE and Von Schulze, AT and Geiger, PC}, title = {Exercise, heat shock proteins and insulin resistance.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203714}, issn = {1471-2970}, mesh = {Animals ; Exercise/*physiology ; Heat-Shock Proteins/*genetics/metabolism ; Humans ; Insulin Resistance/genetics/*physiology ; Mice ; Physical Conditioning, Animal/physiology ; Rats ; }, abstract = {Best known as chaperones, heat shock proteins (HSPs) also have roles in cell signalling and regulation of metabolism. Rodent studies demonstrate that heat treatment, transgenic overexpression and pharmacological induction of HSP72 prevent high-fat diet-induced glucose intolerance and skeletal muscle insulin resistance. Overexpression of skeletal muscle HSP72 in mice has been shown to increase endurance running capacity nearly twofold and increase mitochondrial content by 50%. A positive correlation between HSP72 mRNA expression and mitochondrial enzyme activity has been observed in human skeletal muscle, and HSP72 expression is markedly decreased in skeletal muscle of insulin resistant and type 2 diabetic patients. In addition, decreased levels of HSP72 correlate with insulin resistance and non-alcoholic fatty liver disease progression in livers from obese patients. These data suggest the targeted induction of HSPs could be a therapeutic approach for preventing metabolic disease by maintaining the body's natural stress response. Exercise elicits a number of metabolic adaptations and is a powerful tool in the prevention and treatment of insulin resistance. Exercise training is also a stimulus for increased HSP expression. Although the underlying mechanism(s) for exercise-induced HSP expression are currently unknown, the HSP response may be critical for the beneficial metabolic effects of exercise. Exercise-induced extracellular HSP release may also contribute to metabolic homeostasis by actively restoring HSP72 content in insulin resistant tissues containing low endogenous levels of HSPs.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203713, year = {2018}, author = {Thakur, SS and Swiderski, K and Ryall, JG and Lynch, GS}, title = {Therapeutic potential of heat shock protein induction for muscular dystrophy and other muscle wasting conditions.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203713}, issn = {1471-2970}, mesh = {Animals ; Heat-Shock Proteins/genetics/*therapeutic use ; Humans ; Mice ; Muscular Dystrophy, Duchenne/genetics/*therapy ; Rats ; }, abstract = {Duchenne muscular dystrophy is the most common and severe of the muscular dystrophies, a group of inherited myopathies caused by different genetic mutations leading to aberrant expression or complete absence of cytoskeletal proteins. Dystrophic muscles are prone to injury, and regenerate poorly after damage. Remorseless cycles of muscle fibre breakdown and incomplete repair lead to progressive and severe muscle wasting, weakness and premature death. Many other conditions are similarly characterized by muscle wasting, including sarcopenia, cancer cachexia, sepsis, denervation, burns, and chronic obstructive pulmonary disease. Muscle trauma and loss of mass and physical capacity can significantly compromise quality of life for patients. Exercise and nutritional interventions are unlikely to halt or reverse the conditions, and strategies promoting muscle anabolism have limited clinical acceptance. Heat shock proteins (HSPs) are molecular chaperones that help proteins fold back to their original conformation and restore function. Since many muscle wasting conditions have pathophysiologies where inflammation, atrophy and weakness are indicated, increasing HSP expression in skeletal muscle may have therapeutic potential. This review will provide evidence supporting HSP induction for muscular dystrophy and other muscle wasting conditions.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203712, year = {2018}, author = {Zuehlke, AD and Moses, MA and Neckers, L}, title = {Heat shock protein 90: its inhibition and function.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203712}, issn = {1471-2970}, mesh = {Animals ; HSP90 Heat-Shock Proteins/*genetics/metabolism ; Humans ; Mammals/*genetics ; }, abstract = {The molecular chaperone heat shock protein 90 (Hsp90) facilitates metastable protein maturation, stabilization of aggregation-prone proteins, quality control of misfolded proteins and assists in keeping proteins in activation-competent conformations. Proteins that rely on Hsp90 for function are delivered to Hsp90 utilizing a co-chaperone-assisted cycle. Co-chaperones play a role in client transfer to Hsp90, Hsp90 ATPase regulation and stabilization of various Hsp90 conformational states. Many of the proteins chaperoned by Hsp90 (Hsp90 clients) are essential for the progression of various diseases, including cancer, Alzheimer's disease and other neurodegenerative diseases, as well as viral and bacterial infections. Given the importance of these clients in different diseases and their dynamic interplay with the chaperone machinery, it has been suggested that targeting Hsp90 and its respective co-chaperones may be an effective method for combating a large range of illnesses.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203711, year = {2018}, author = {Shevtsov, M and Huile, G and Multhoff, G}, title = {Membrane heat shock protein 70: a theranostic target for cancer therapy.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203711}, issn = {1471-2970}, mesh = {HSP70 Heat-Shock Proteins/*genetics/metabolism ; Neoplasms/*therapy ; Theranostic Nanomedicine/*methods ; }, abstract = {Members of the 70 kDa stress protein family are found in nearly all subcellular compartments of nucleated cells where they fulfil a number of chaperoning functions. Heat shock protein 70 (HSP70), also termed HSPA1A, the major stress-inducible member of this family is overexpressed in a large variety of different tumour types. Apart from its intracellular localization, a tumour-selective HSP70 membrane expression has been determined. A membrane HSP70-positive tumour phenotype is associated with aggressiveness and therapy resistance, but also serves as a recognition structure for targeted therapies. Furthermore, membrane-bound and extracellularly residing HSP70 derived from tumour cells play pivotal roles in eliciting anti-tumour immune responses. Herein, we want to shed light on the multiplicity of different activities of HSP70, depending on its intracellular, membrane and extracellular localization with the goal to use membrane HSP70 as a target for novel therapies including nanoparticle-based approaches for the treatment of cancer.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203710, year = {2018}, author = {Dai, C}, title = {The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203710}, issn = {1471-2970}, mesh = {Animals ; Carcinogenesis/*genetics/metabolism ; Heat Shock Transcription Factors/*genetics/metabolism ; Humans ; Mammals/*genetics/metabolism ; Neoplastic Cells, Circulating/*metabolism ; }, abstract = {The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSF1-targeting strategies.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203709, year = {2018}, author = {Calderwood, SK}, title = {Heat shock proteins and cancer: intracellular chaperones or extracellular signalling ligands?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203709}, issn = {1471-2970}, mesh = {Gene Expression Regulation/*genetics ; Heat-Shock Proteins/*genetics/metabolism ; Ligands ; Molecular Chaperones/genetics/metabolism ; Neoplasms/genetics/*physiopathology ; *Signal Transduction ; }, abstract = {Heat shock proteins (HSPs) are found at elevated concentrations in tumour cells, and this increase reflects the proteotoxic stress experienced by the cells due to expanding levels of the mutated oncoproteins that drive tumorigenesis. The protection of oncogenic proteins by HSPs offers a window of vulnerability in tumour metabolism that has been exploited using Hsp90-targeting drugs. Such compounds have been shown to cause inhibition and degradation of a wide range of proteins essential for oncogenesis. Recently, Hsp90 has also been shown to be secreted by tumour cells and to interact in autocrine or paracrine manners with the surfaces of adjacent cells, leading to increased growth and metastasis. Future studies will address a number of key questions associated with these findings, including the relative importance of intracellular versus extracellular HSPs in tumorigenesis, as well as overcoming potential problems with normal tissue toxicity associated with Hsp90 drugs. Targeting individual members of HSP families and inactivating extracellular HSPs may be desirable future approaches that offer increased selectivity in targeting HSPs in cancer.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203708, year = {2018}, author = {Jeffery, CJ}, title = {Protein moonlighting: what is it, and why is it important?.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203708}, issn = {1471-2970}, mesh = {Animals ; Eukaryota/genetics/metabolism ; Heat-Shock Proteins/*genetics/metabolism ; Humans ; }, abstract = {Members of the GroEL/HSP60 protein family have been studied for many years because of their critical roles as ATP-dependent molecular chaperones, so it might come as a surprise that some have important functions in ATP-poor conditions, for example, when secreted outside the cell. At least some members of each of the HSP10, HSP70, HSP90, HSP100 and HSP110 heat shock protein families are also 'moonlighting proteins'. Moonlighting proteins exhibit more than one physiologically relevant biochemical or biophysical function within one polypeptide chain. In this class of multifunctional proteins, the multiple functions are not due to gene fusions or multiple proteolytic fragments. Several hundred moonlighting proteins have been identified, and they include a diverse set of proteins with a large variety of functions. Some participate in multiple biochemical processes by using an active site pocket for catalysis and a different part of the protein's surface to interact with other proteins. Moonlighting proteins play a central role in many diseases, and the development of novel treatments would be aided by more information addressing current questions, for example, how some are targeted to multiple cellular locations and how a single function can be targeted by therapeutics without targeting a function not involved in disease.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203707, year = {2018}, author = {Pockley, AG and Henderson, B}, title = {Extracellular cell stress (heat shock) proteins-immune responses and disease: an overview.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203707}, issn = {1471-2970}, mesh = {Disease/*genetics ; Heat-Shock Proteins/*genetics ; Humans ; Immunity ; *Immunity, Innate ; Signal Transduction/*immunology ; }, abstract = {Extracellular cell stress proteins are highly conserved phylogenetically and have been shown to act as powerful signalling agonists and receptors for selected ligands in several different settings. They also act as immunostimulatory 'danger signals' for the innate and adaptive immune systems. Other studies have shown that cell stress proteins and the induction of immune reactivity to self-cell stress proteins can attenuate disease processes. Some proteins (e.g. Hsp60, Hsp70, gp96) exhibit both inflammatory and anti-inflammatory properties, depending on the context in which they encounter responding immune cells. The burgeoning literature reporting the presence of stress proteins in a range of biological fluids in healthy individuals/non-diseased settings, the association of extracellular stress protein levels with a plethora of clinical and pathological conditions and the selective expression of a membrane form of Hsp70 on cancer cells now supports the concept that extracellular cell stress proteins are involved in maintaining/regulating organismal homeostasis and in disease processes and phenotype. Cell stress proteins, therefore, form a biologically complex extracellular cell stress protein network having diverse biological, homeostatic and immunomodulatory properties, the understanding of which offers exciting opportunities for delivering novel approaches to predict, identify, diagnose, manage and treat disease.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203706, year = {2018}, author = {Edkins, AL and Price, JT and Pockley, AG and Blatch, GL}, title = {Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1738}, pages = {}, pmid = {29203706}, issn = {1471-2970}, mesh = {Chronic Disease/*prevention & control ; Heat-Shock Proteins/*genetics/metabolism ; Neoplasms ; Wit and Humor as Topic ; }, abstract = {Many heat shock proteins (HSPs) are essential to survival as a consequence of their role as molecular chaperones, and play a critical role in maintaining cellular proteostasis by integrating the fundamental processes of protein folding and degradation. HSPs are arguably among the most prominent classes of proteins that have been broadly linked to many human disorders, with changes in their expression profile and/or intracellular/extracellular location now being described as contributing to the pathogenesis of a number of different diseases. Although the concept was initially controversial, it is now widely accepted that HSPs have additional biological functions over and above their role in proteostasis (so-called 'protein moonlighting'). Most importantly, these new insights are enlightening our understanding of biological processes in health and disease, and revealing novel and exciting therapeutic opportunities. This theme issue draws on therapeutic insights from established research on HSPs in cancer and other non-communicable disorders, with an emphasis on how the intracellular function of HSPs contrasts with their extracellular properties and function, and interrogates their potential diagnostic and therapeutic value to the prevention, management and treatment of chronic diseases.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'.}, } @article {pmid29203662, year = {2018}, author = {Patton, JB and Bonne-Année, S and Deckman, J and Hess, JA and Torigian, A and Nolan, TJ and Wang, Z and Kliewer, SA and Durham, AC and Lee, JJ and Eberhard, ML and Mangelsdorf, DJ and Lok, JB and Abraham, D}, title = {Methylprednisolone acetate induces, and Δ7-dafachronic acid suppresses, Strongyloides stercoralis hyperinfection in NSG mice.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {204-209}, pmid = {29203662}, issn = {1091-6490}, support = {R01 AI022662/AI/NIAID NIH HHS/United States ; R21 AI105856/AI/NIAID NIH HHS/United States ; R01 AI050668/AI/NIAID NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; R01 DK067158/DK/NIDDK NIH HHS/United States ; R33 AI105856/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cholestenes/adverse effects/*pharmacology ; Female ; Methylprednisolone/adverse effects/*analogs & derivatives/pharmacology ; Methylprednisolone Acetate ; Mice ; Strongyloides stercoralis/*immunology ; Strongyloidiasis/*drug therapy/*immunology/pathology ; }, abstract = {Strongyloides stercoralis hyperinfection causes high mortality rates in humans, and, while hyperinfection can be induced by immunosuppressive glucocorticoids, the pathogenesis remains unknown. Since immunocompetent mice are resistant to infection with S. stercoralis, we hypothesized that NSG mice, which have a reduced innate immune response and lack adaptive immunity, would be susceptible to the infection and develop hyperinfection. Interestingly, despite the presence of large numbers of adult and first-stage larvae in S. stercoralis-infected NSG mice, no hyperinfection was observed even when the mice were treated with a monoclonal antibody to eliminate residual granulocyte activity. NSG mice were then infected with third-stage larvae and treated for 6 wk with methylprednisolone acetate (MPA), a synthetic glucocorticoid. MPA treatment of infected mice resulted in 50% mortality and caused a significant >10-fold increase in the number of parasitic female worms compared with infected untreated mice. In addition, autoinfective third-stage larvae, which initiate hyperinfection, were found in high numbers in MPA-treated, but not untreated, mice. Remarkably, treatment with Δ7-dafachronic acid, an agonist of the parasite nuclear receptor Ss-DAF-12, significantly reduced the worm burden in MPA-treated mice undergoing hyperinfection with S. stercoralis Overall, this study provides a useful mouse model for S. stercoralis autoinfection and suggests a therapeutic strategy for treating lethal hyperinfection.}, } @article {pmid29203212, year = {2018}, author = {Castrillo, M and Luque, EM and Pardo-Medina, J and Limón, MC and Corrochano, LM and Avalos, J}, title = {Transcriptional basis of enhanced photoinduction of carotenoid biosynthesis at low temperature in the fungus Neurospora crassa.}, journal = {Research in microbiology}, volume = {169}, number = {2}, pages = {78-89}, doi = {10.1016/j.resmic.2017.11.003}, pmid = {29203212}, issn = {1769-7123}, mesh = {Carotenoids/*biosynthesis ; Cold Temperature ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal/radiation effects ; Light ; Neurospora crassa/genetics/*metabolism/radiation effects ; *Transcription, Genetic/radiation effects ; }, abstract = {Stimulation by light of carotenoid biosynthesis in the mycelia of the fungus Neurospora crassa starts with transient transcriptional induction of the structural genes of the pathway triggered by the White Collar photoreceptor complex. Most studies on this process were carried out under standard growth conditions, but photoinduced carotenoid accumulation is more efficient if the fungus is incubated at low temperatures, from 6 to 12 °C. We have investigated the transcriptional photoresponse at 8 °C of the genes for proteins that participate in the carotenoid pathway. Exposure to light pulses of different light intensities revealed higher sensitivity if the mycelia were subsequently incubated at 8 °C compared to 30 °C. Illumination of precooled mycelia resulted in delayed kinetics of mRNA accumulation for the structural genes, and high mRNA accumulation for a longer time. Additionally, after a light pulse, stronger reduction in mRNAs for carotenoid genes was observed at 30 °C compared to 8 °C. A similar pattern was found for mRNAs of the photoreceptor genes wc-1 and vvd, the latter involved in photoadaptation. These results suggest that the increased efficiency in carotenoid photoinduction at low temperature is due to the higher mRNA levels of the structural genes under these conditions.}, } @article {pmid29202336, year = {2018}, author = {Johnson, KS and Ottemann, KM}, title = {Colonization, localization, and inflammation: the roles of H. pylori chemotaxis in vivo.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {51-57}, pmid = {29202336}, issn = {1879-0364}, support = {R01 AI116946/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Bacterial Proteins/genetics/metabolism ; Chemoreceptor Cells/metabolism ; *Chemotaxis ; Gastric Mucosa/microbiology ; Gastritis/microbiology ; Helicobacter Infections/immunology/microbiology/therapy ; Helicobacter pylori/immunology/*metabolism ; Host-Pathogen Interactions/immunology/physiology ; Humans ; *Inflammation ; Mice ; Signal Transduction ; Stomach Neoplasms/microbiology ; }, abstract = {Helicobacter pylori is a Gram-negative bacterium that infects half of the world's population, causing gastritis, peptic ulcers, and gastric cancer. To establish chronic stomach infection, H. pylori utilizes chemotaxis, driven by a conserved signal transduction system. Chemotaxis allows H. pylori to sense an array of environmental and bacterial signals within the stomach, guiding its motility towards its preferred niche within the gastric mucosa and glands. Fine-tuned localization, regulated by the chemotaxis system, enables robust colonization during the acute stage of infection. During chronic infection, chemotaxis helps maintain bacterial populations and modulates the host immune response. Given its importance in host colonization and disease, chemotaxis is an attractive target for future treatments against H. pylori infections.}, } @article {pmid29202176, year = {2018}, author = {Ludewig-Klingner, AK and Michael, V and Jarek, M and Brinkmann, H and Petersen, J}, title = {Distribution and Evolution of Peroxisomes in Alveolates (Apicomplexa, Dinoflagellates, Ciliates).}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {1-13}, pmid = {29202176}, issn = {1759-6653}, mesh = {Apicomplexa/*genetics/physiology ; Biological Evolution ; Ciliophora/*genetics/physiology ; Dinoflagellida/*genetics/physiology ; Metabolic Networks and Pathways ; Peroxins/analysis/genetics/metabolism ; Peroxisomes/*genetics/metabolism ; *Phylogeny ; Transcriptome ; }, abstract = {The peroxisome was the last organelle to be discovered and five decades later it is still the Cinderella of eukaryotic compartments. Peroxisomes have a crucial role in the detoxification of reactive oxygen species, the beta-oxidation of fatty acids, and the biosynthesis of etherphospholipids, and they are assumed to be present in virtually all aerobic eukaryotes. Apicomplexan parasites including the malaria and toxoplasmosis agents were described as the first group of mitochondriate protists devoid of peroxisomes. This study was initiated to reassess the distribution and evolution of peroxisomes in the superensemble Alveolata (apicomplexans, dinoflagellates, ciliates). We established transcriptome data from two chromerid algae (Chromera velia, Vitrella brassicaformis), and two dinoflagellates (Prorocentrum minimum, Perkinsus olseni) and identified the complete set of essential peroxins in all four reference species. Our comparative genome analysis provides unequivocal evidence for the presence of peroxisomes in Toxoplasma gondii and related genera. Our working hypothesis of a common peroxisomal origin of all alveolates is supported by phylogenetic analyses of essential markers such as the import receptor Pex5. Vitrella harbors the most comprehensive set of peroxisomal proteins including the catalase and the glyoxylate cycle and it is thus a promising model organism to investigate the functional role of this organelle in Apicomplexa.}, } @article {pmid29202174, year = {2018}, author = {Wragg, D and Techer, MA and Canale-Tabet, K and Basso, B and Bidanel, JP and Labarthe, E and Bouchez, O and Le Conte, Y and Clémencet, J and Delatte, H and Vignal, A}, title = {Autosomal and Mitochondrial Adaptation Following Admixture: A Case Study on the Honeybees of Reunion Island.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {220-238}, pmid = {29202174}, issn = {1759-6653}, mesh = {Acclimatization ; Adaptation, Physiological ; Animals ; Bees/*genetics/physiology ; DNA, Mitochondrial/genetics ; Female ; Genome, Insect ; Genome, Mitochondrial ; Male ; Mitochondria/*genetics/metabolism ; Reunion ; }, abstract = {The honeybee population of the tropical Reunion Island is a genetic admixture of the Apis mellifera unicolor subspecies, originally described in Madagascar, and of European subspecies, mainly A. m. carnica and A. m. ligustica, regularly imported to the island since the late 19th century. We took advantage of this population to study genetic admixing of the tropical-adapted indigenous and temperate-adapted European genetic backgrounds. Whole genome sequencing of 30 workers and 6 males from Reunion, compared with samples from Europe, Madagascar, Mauritius, Rodrigues, and the Seychelles, revealed the Reunion honeybee population to be composed on an average of 53.2 ± 5.9% A. m. unicolor nuclear genomic background, the rest being mainly composed of A. m. carnica and to a lesser extent A. m. ligustica. In striking contrast to this, only 1 out of the 36 honeybees from Reunion had a mitochondrial genome of European origin, suggesting selection has favored the A. m. unicolor mitotype, which is possibly better adapted to the island's bioclimate. Local ancestry was determined along the chromosomes for all Reunion samples, and a test for preferential selection for the A. m. unicolor or European background revealed 15 regions significantly associated with the A. m. unicolor lineage and 9 regions with the European lineage. Our results provide insights into the long-term consequences of introducing exotic specimen on the nuclear and mitochondrial genomes of locally adapted populations.}, } @article {pmid29199285, year = {2018}, author = {Trenkmann, M}, title = {Gene expression: SPOTting single RNA molecules transcriptome-wide.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {7}, pmid = {29199285}, issn = {1471-0064}, } @article {pmid29199284, year = {2018}, author = {Baumann, K}, title = {Stem cells: Regenerating the skin of a young patient.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {4-5}, pmid = {29199284}, issn = {1471-0064}, } @article {pmid29199283, year = {2018}, author = {Doench, JG}, title = {Am I ready for CRISPR? A user's guide to genetic screens.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {67-80}, pmid = {29199283}, issn = {1471-0064}, abstract = {Exciting new technologies are often self-limiting in their rollout, as access to state-of-the-art instrumentation or the need for years of hands-on experience, for better or worse, ensures slow adoption by the community. CRISPR technology, however, presents the opposite dilemma, where the simplicity of the system enabled the parallel development of many applications, improvements and derivatives, and new users are now presented with an almost paralyzing abundance of choices. This Review intends to guide users through the process of applying CRISPR technology to their biological problems of interest, especially in the context of discovering gene function at scale.}, } @article {pmid29199282, year = {2018}, author = {Perdigoto, C}, title = {Pathogen genomics: Genomics in the time of cholera.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {3}, pmid = {29199282}, issn = {1471-0064}, } @article {pmid29199108, year = {2018}, author = {Hughes, DF and Tolley, KA and Behangana, M and Lukwago, W and Menegon, M and Dehling, JM and Stipala, J and Tilbury, CR and Khan, AM and Kusamba, C and Greenbaum, E}, title = {Cryptic diversity in Rhampholeon boulengeri (Sauria: Chamaeleonidae), a pygmy chameleon from the Albertine Rift biodiversity hotspot.}, journal = {Molecular phylogenetics and evolution}, volume = {122}, number = {}, pages = {125-141}, pmid = {29199108}, issn = {1095-9513}, support = {G12 MD007592/MD/NIMHD NIH HHS/United States ; }, mesh = {Africa, Central ; Animals ; *Biodiversity ; DNA/chemistry/isolation & purification/metabolism ; DNA, Mitochondrial/genetics ; Ecosystem ; Gene Flow ; Lizards/*classification/genetics ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; }, abstract = {Several biogeographic barriers in the Central African highlands have reduced gene flow among populations of many terrestrial species in predictable ways. Yet, a comprehensive understanding of mechanisms underlying species divergence in the Afrotropics can be obscured by unrecognized levels of cryptic diversity, particularly in widespread species. We implemented a multilocus phylogeographic approach to examine diversity within the widely distributed Central African pygmy chameleon, Rhampholeon boulengeri. Gene-tree analyses coupled with a comparative coalescent-based species delimitation framework revealed R. boulengeri as a complex of at least six genetically distinct species. The spatiotemporal speciation patterns for these cryptic species conform to general biogeographic hypotheses supporting vicariance as the main factor behind patterns of divergence in the Albertine Rift, a biodiversity hotspot in Central Africa. However, we found that parapatric species and sister species inhabited adjacent habitats, but were found in largely non-overlapping elevational ranges in the Albertine Rift, suggesting that differentiation in elevation was also an important mode of divergence. The phylogeographic patterns recovered for the genus-level phylogeny provide additional evidence for speciation by isolation in forest refugia, and dating estimates indicated that the Miocene was a significant period for this diversification. Our results highlight the importance of investigating cryptic diversity in widespread species to improve understanding of diversification patterns in environmentally diverse regions such as the montane Afrotropics.}, } @article {pmid29199107, year = {2018}, author = {Solano-Zavaleta, I and Nieto-Montes de Oca, A}, title = {Species limits in the Morelet's Alligator lizard (Anguidae: Gerrhonotinae).}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {16-27}, doi = {10.1016/j.ympev.2017.11.011}, pmid = {29199107}, issn = {1095-9513}, mesh = {Alligators and Crocodiles/*physiology ; Animals ; Bayes Theorem ; Cell Nucleus/genetics ; Central America ; DNA, Mitochondrial/genetics ; Lizards/genetics/*physiology ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Species Specificity ; Time Factors ; }, abstract = {The widely distributed, Central American anguid lizard Mesaspis moreletii is currently recognized as a polytypic species with five subspecies (M. m. fulvus, M. m. moreletii, M. m. rafaeli, M. m. salvadorensis, and M. m. temporalis). We reevaluated the species limits within Mesaspis moreletii using DNA sequences of one mitochondrial and three nuclear genes. The multi-locus data set included samples of all of the subspecies of M. moreletii, the other species of Mesaspis in Central America (M. cuchumatanus and M. monticola), and some populations assignable to M. moreletii but of uncertain subspecific identity from Honduras and Nicaragua. We first used a tree-based method for delimiting species based on mtDNA data to identify potential evolutionary independent lineages, and then analized the multilocus dataset with two species delimitation methods that use the multispecies coalescent model to evaluate different competing species delimitation models: the Bayes factors species delimitation method (BFD) implemented in ∗BEAST, and the Bayesian Phylogenetics and Phylogeography (BP&P) method. Our results suggest that M. m. moreletii, M. m. rafaeli, M. m. salvadorensis, and M. m. temporalis represent distinct evolutionary independent lineages, and that the populations of uncertain status from Honduras and Nicaragua may represent additional undescribed species. Our results also suggest that M. m. fulvus is a synonym of M. m. moreletii. The biogeography of the Central American lineages of Mesaspis is discussed.}, } @article {pmid29199106, year = {2018}, author = {Bruxaux, J and Gabrielli, M and Ashari, H and Prŷs-Jones, R and Joseph, L and Milá, B and Besnard, G and Thébaud, C}, title = {Recovering the evolutionary history of crowned pigeons (Columbidae: Goura): Implications for the biogeography and conservation of New Guinean lowland birds.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {248-258}, doi = {10.1016/j.ympev.2017.11.022}, pmid = {29199106}, issn = {1095-9513}, mesh = {Animals ; Columbidae/*classification/genetics ; DNA, Mitochondrial/chemistry/genetics/metabolism ; *Evolution, Molecular ; Genetic Variation ; Genome, Mitochondrial ; New Guinea ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Assessing the relative contributions of immigration and diversification into the buildup of species diversity is key to understanding the role of historical processes in driving biogeographical and diversification patterns in species-rich regions. Here, we investigated how colonization, in situ speciation, and extinction history may have generated the present-day distribution and diversity of Goura crowned pigeons (Columbidae), a group of large forest-dwelling pigeons comprising four recognized species that are all endemic to New Guinea. We used a comprehensive geographical and taxonomic sampling based mostly on historical museum samples, and shallow shotgun sequencing, to generate complete mitogenomes, nuclear ribosomal clusters and independent nuclear conserved DNA elements. We used these datasets independently to reconstruct molecular phylogenies. Divergence time estimates were obtained using mitochondrial data only. All analyses revealed similar genetic divisions within the genus Goura and recovered as monophyletic groups the four species currently recognized, providing support for recent taxonomic changes based on differences in plumage characters. These four species are grouped into two pairs of strongly supported sister species, which were previously not recognized as close relatives: Goura sclaterii with Goura cristata, and Goura victoria with Goura scheepmakeri. While the geographical origin of the Goura lineage remains elusive, the crown age of 5.73 Ma is consistent with present-day species diversity being the result of a recent diversification within New Guinea. Although the orogeny of New Guinea's central cordillera must have played a role in driving diversification in Goura, cross-barrier dispersal seems more likely than vicariance to explain the speciation events having led to the four current species. Our results also have important conservation implications. Future assessments of the conservation status of Goura species should consider threat levels following the taxonomic revision proposed by del Hoyo and Collar (HBW and BirdLife International illustrated checklist of the birds of the world 1: non-passerines, 2014), which we show to be fully supported by genomic data. In particular, distinguishing G. sclaterii from G. scheepmakeri seems to be particularly relevant.}, } @article {pmid29199105, year = {2018}, author = {Jønsson, KA and Blom, MPK and Päckert, M and Ericson, PGP and Irestedt, M}, title = {Relicts of the lost arc: High-throughput sequencing of the Eutrichomyias rowleyi (Aves: Passeriformes) holotype uncovers an ancient biogeographic link between the Philippines and Fiji.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {28-32}, doi = {10.1016/j.ympev.2017.11.021}, pmid = {29199105}, issn = {1095-9513}, mesh = {Animals ; Australia ; Fiji ; High-Throughput Nucleotide Sequencing/*methods ; Islands ; Passeriformes/*genetics ; Philippines ; Phylogeny ; *Phylogeography ; Time Factors ; }, abstract = {Molecular studies have revealed a number of cases in which traditional assessments of evolutionary relationships have been incorrect. This has implications not only for systematics and taxonomy but also for our understanding of how diversity patterns on Earth have been formed. Here, we use high-throughput sequencing technology to obtain molecular data from the holotype specimen of the elusive Eutrichomyias rowleyi, which is endemic to the Indonesian island of Sangihe. We show that E. rowleyi unexpectedly is a member of the family Lamproliidae, which dates back some 20 Million years and only include two other species, Lamprolia victoriae from Fiji and Chaetorhynchus papuensis from New Guinea. Tectonic reconstructions suggest that the Melanesian island arc, which included land masses on the northern edge of the Australian plate (present day New Guinea) stretched as a string of islands from the Philippines (including proto-Sangihe) to Fiji from 25 to 20 My. Consequently, our results are indicative of an ancient distribution along the Melanesian island arc followed by relictualization, which led to members of the Lamproliidae to be distributed on widely separated islands across the Indo-Pacific.}, } @article {pmid29198650, year = {2018}, author = {Bergé, M and Viollier, PH}, title = {End-in-Sight: Cell Polarization by the Polygamic Organizer PopZ.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {363-375}, doi = {10.1016/j.tim.2017.11.007}, pmid = {29198650}, issn = {1878-4380}, abstract = {Understanding how asymmetries in cellular constituents are achieved and how such positional information directs the construction of structures in a nonrandom fashion is a fundamental problem in cell biology. The recent identification of determinants that self-assemble into macromolecular complexes at the bacterial cell pole provides new insight into the underlying organizational principles in bacterial cells. Specifically, polarity studies in host-associated or free-living α-proteobacteria, a lineage of Gram-negative (diderm) bacteria, reveals that functional and cytological mono- and bipolarity is often conferred by the multivalent polar organizer PopZ, originally identified as a component of a polar chromosome anchor in the cell cycle model system Caulobacter crescentus. PopZ-dependent polarization appears to be widespread and also functional in obligate intracellular pathogens. Here, we discuss how PopZ polarization and the establishment of polar complexes occurs, and we detail the physiological roles of these complexes.}, } @article {pmid29198566, year = {2018}, author = {Oliveira, CR and Lemaitre, R and Murawala, P and Tazaki, A and Drechsel, DN and Tanaka, EM}, title = {Pseudotyped baculovirus is an effective gene expression tool for studying molecular function during axolotl limb regeneration.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {262-275}, doi = {10.1016/j.ydbio.2017.10.008}, pmid = {29198566}, issn = {1095-564X}, mesh = {Ambystoma mexicanum/genetics/*physiology ; Amputation ; Animals ; Forelimb/*physiology ; Gene Expression Profiling ; *Gene Expression Regulation ; Genes, Reporter ; Genes, Synthetic ; Genetic Vectors/*genetics ; Hedgehog Proteins/genetics/physiology ; Homeodomain Proteins/physiology ; Humans ; Membrane Glycoproteins/physiology ; Mesoderm/cytology ; Nucleopolyhedrovirus/*genetics ; Recombinant Proteins/metabolism ; Regeneration/genetics/*physiology ; *Transduction, Genetic ; Transgenes ; Viral Envelope Proteins/physiology ; Wound Healing/genetics/physiology ; }, abstract = {Axolotls can regenerate complex structures through recruitment and remodeling of cells within mature tissues. Accessing the underlying mechanisms at a molecular resolution is crucial to understand how injury triggers regeneration and how it proceeds. However, gene transformation in adult tissues can be challenging. Here we characterize the use of pseudotyped baculovirus (BV) as an effective gene transfer method both for cells within mature limb tissue and within the blastema. These cells remain competent to participate in regeneration after transduction. We further characterize the effectiveness of BV for gene overexpression studies by overexpressing Shh in the blastema, which yields a high penetrance of classic polydactyly phenotypes. Overall, our work establishes BV as a powerful tool to access gene function in axolotl limb regeneration.}, } @article {pmid29198565, year = {2018}, author = {Lai, AG and Aboobaker, AA}, title = {EvoRegen in animals: Time to uncover deep conservation or convergence of adult stem cell evolution and regenerative processes.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {118-131}, doi = {10.1016/j.ydbio.2017.10.010}, pmid = {29198565}, issn = {1095-564X}, support = {MR/M000133/1//Medical Research Council/United Kingdom ; BB/K007564/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adult Germline Stem Cells/physiology ; Adult Stem Cells/*physiology ; Animals ; Argonaute Proteins/physiology ; *Biological Evolution ; Cell Lineage ; Embryonic Development ; Humans ; Invertebrates/cytology/physiology ; Models, Animal ; Models, Biological ; Multipotent Stem Cells/physiology ; Phylogeny ; Pluripotent Stem Cells/physiology ; RNA, Small Interfering/genetics ; Regeneration/*physiology ; Species Specificity ; }, abstract = {How do animals regenerate specialised tissues or their entire body after a traumatic injury, how has this ability evolved and what are the genetic and cellular components underpinning this remarkable feat? While some progress has been made in understanding mechanisms, relatively little is known about the evolution of regenerative ability. Which elements of regeneration are due to lineage specific evolutionary novelties or have deeply conserved roots within the Metazoa remains an open question. The renaissance in regeneration research, fuelled by the development of modern functional and comparative genomics, now enable us to gain a detailed understanding of both the mechanisms and evolutionary forces underpinning regeneration in diverse animal phyla. Here we review existing and emerging model systems, with the focus on invertebrates, for studying regeneration. We summarize findings across these taxa that tell us something about the evolution of adult stem cell types that fuel regeneration and the growing evidence that many highly regenerative animals harbor adult stem cells with a gene expression profile that overlaps with germline stem cells. We propose a framework in which regenerative ability broadly evolves through changes in the extent to which stem cells generated through embryogenesis are maintained into the adult life history.}, } @article {pmid29198564, year = {2018}, author = {Thalheim, T and Quaas, M and Herberg, M and Braumann, UD and Kerner, C and Loeffler, M and Aust, G and Galle, J}, title = {Linking stem cell function and growth pattern of intestinal organoids.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {254-261}, doi = {10.1016/j.ydbio.2017.10.013}, pmid = {29198564}, issn = {1095-564X}, mesh = {Animals ; Apoptosis ; Biomechanical Phenomena ; Cell Adhesion ; Cell Shape ; *Computer Simulation ; Intestines/*cytology ; Mice ; Mice, Inbred C57BL ; *Models, Biological ; Organoids/*growth & development ; Polymers ; Receptors, Notch/physiology ; Regeneration/physiology ; Stem Cell Niche ; Stem Cells/*physiology ; Tissue Culture Techniques ; Wnt Proteins/physiology ; Wnt Signaling Pathway ; }, abstract = {Intestinal stem cells (ISCs) require well-defined signals from their environment in order to carry out their specific functions. Most of these signals are provided by neighboring cells that form a stem cell niche, whose shape and cellular composition self-organize. Major features of this self-organization can be studied in ISC-derived organoid culture. In this system, manipulation of essential pathways of stem cell maintenance and differentiation results in well-described growth phenotypes. We here provide an individual cell-based model of intestinal organoids that enables a mechanistic explanation of the observed growth phenotypes. In simulation studies of the 3D structure of expanding organoids, we investigate interdependences between Wnt- and Notch-signaling which control the shape of the stem cell niche and, thus, the growth pattern of the organoids. Similar to in vitro experiments, changes of pathway activities alter the cellular composition of the organoids and, thereby, affect their shape. Exogenous Wnt enforces transitions from branched into a cyst-like growth pattern; known to occur spontaneously during long term organoid expansion. Based on our simulation results, we predict that the cyst-like pattern is associated with biomechanical changes of the cells which assign them a growth advantage. The results suggest ongoing stem cell adaptation to in vitro conditions during long term expansion by stabilizing Wnt-activity. Our study exemplifies the potential of individual cell-based modeling in unraveling links between molecular stem cell regulation and 3D growth of tissues. This kind of modeling combines experimental results in the fields of stem cell biology and cell biomechanics constituting a prerequisite for a better understanding of tissue regeneration as well as developmental processes.}, } @article {pmid29198563, year = {2018}, author = {Flora, P and Schowalter, S and Wong-Deyrup, S and DeGennaro, M and Nasrallah, MA and Rangan, P}, title = {Transient transcriptional silencing alters the cell cycle to promote germline stem cell differentiation in Drosophila.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {84-95}, pmid = {29198563}, issn = {1095-564X}, support = {R01 GM111779/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/*physiology ; Cyclin B/biosynthesis/genetics ; Drosophila Proteins/biosynthesis/genetics ; Drosophila melanogaster ; G2 Phase/*physiology ; Gene Silencing/*physiology ; Germ Cells/cytology/*metabolism ; Heterochromatin/genetics/metabolism ; Stem Cells/cytology/*metabolism ; }, abstract = {Transcriptional silencing is a conserved process used by embryonic germ cells to repress somatic fate and maintain totipotency and immortality. In Drosophila, this transcriptional silencing is mediated by polar granule component (pgc). Here, we show that in the adult ovary, pgc is required for timely germline stem cell (GSC) differentiation. Pgc is expressed transiently in the immediate GSC daughter (pre-cystoblast), where it mediates a pulse of transcriptional silencing. This transcriptional silencing mediated by pgc indirectly promotes the accumulation of Cyclin B (CycB) and cell cycle progression into late-G2 phase, when the differentiation factor bag of marbles (bam) is expressed. Pgc mediated accumulation of CycB is also required for heterochromatin deposition, which protects the germ line genome against selfish DNA elements. Our results suggest that transient transcriptional silencing in the pre-cystoblast "re-programs" it away from self-renewal and toward the gamete differentiation program.}, } @article {pmid29198471, year = {2018}, author = {Foote, AD}, title = {Sympatric Speciation in the Genomic Era.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {2}, pages = {85-95}, doi = {10.1016/j.tree.2017.11.003}, pmid = {29198471}, issn = {1872-8383}, mesh = {Animals ; *Gene Flow ; *Genetic Speciation ; Genomics ; Invertebrates/genetics ; Plants/genetics ; *Reproductive Isolation ; *Sympatry ; Vertebrates/genetics ; }, abstract = {Sympatric speciation has been of key interest to biologists investigating how natural and sexual selection drive speciation without the confounding variable of geographic isolation. The advent of the genomic era has provided a more nuanced and quantitative understanding of the different and often complex modes of speciation by which sympatric sister taxa arose, and a reassessment of some of the most compelling empirical case studies of sympatric speciation. However, I argue that genomic studies based on contemporary populations may never be able to provide unequivocal evidence of true primary sympatric speciation, and there is a need to incorporate palaeogenomic studies into this field. This inability to robustly distinguish cases of primary and secondary 'divergence with gene flow' may be inconsequential, as both are useful for understanding the role of large effect barrier loci in the progression from localised genic isolation to genome-wide reproductive isolation. I argue that they can be of equivalent interest due to shared underlying mechanisms driving divergence and potentially leaving similar patterns of coalescence.}, } @article {pmid29198378, year = {2018}, author = {Matz, MV}, title = {Fantastic Beasts and How To Sequence Them: Ecological Genomics for Obscure Model Organisms.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {121-132}, doi = {10.1016/j.tig.2017.11.002}, pmid = {29198378}, issn = {0168-9525}, mesh = {Adaptation, Biological/genetics ; Animals ; Biological Evolution ; DNA Methylation ; Ecology ; Gene Ontology ; *Genetics, Population ; *Genome ; Genomics/instrumentation/*methods ; High-Throughput Nucleotide Sequencing/economics/*methods/trends ; *Models, Animal ; Molecular Sequence Annotation ; }, abstract = {The application of genomic approaches to 'obscure model organisms' (OMOs), meaning species with no prior genomic resources, enables increasingly sophisticated studies of the genomic basis of evolution, acclimatization, and adaptation in real ecological contexts. I consider here ecological questions that can be addressed using OMOs, and indicate optimal sequencing and data-handling solutions for each case. With this I hope to promote the diversity of OMO-based projects that would capitalize on the peculiarities of the natural history of OMOs and could feasibly be completed within the scope of a single PhD thesis.}, } @article {pmid29197823, year = {2018}, author = {Madsen, JS and Sørensen, SJ and Burmølle, M}, title = {Bacterial social interactions and the emergence of community-intrinsic properties.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {104-109}, doi = {10.1016/j.mib.2017.11.018}, pmid = {29197823}, issn = {1879-0364}, mesh = {Bacteria/genetics ; *Bacterial Physiological Phenomena ; Biofilms ; Environmental Microbiology ; Microbial Consortia/genetics/*physiology ; *Microbial Interactions ; }, abstract = {Bacterial communities are dominated and shaped by social interactions, which facilitate the emergence of properties observed only in the community setting. Such community-intrinsic properties impact not only the phenotypes of cells in a community, but also community composition and function, and are thus likely to affect a potential host. Studying community-intrinsic properties is, therefore, important for furthering our understanding of clinical, applied and environmental microbiology. Here, we provide recent examples of research investigating community-intrinsic properties, focusing mainly on community composition and interactions in multispecies biofilms. We hereby wish to emphasize the importance of studying social interactions in settings where community-intrinsic properties are likely to emerge.}, } @article {pmid29197684, year = {2018}, author = {Deepak, V and Karanth, P}, title = {Aridification driven diversification of fan-throated lizards from the Indian subcontinent.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {53-62}, doi = {10.1016/j.ympev.2017.11.016}, pmid = {29197684}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Body Size ; Climate Change ; *Ecosystem ; Fossils ; Geography ; India ; Lizards/anatomy & histology/*classification ; Phylogeny ; Species Specificity ; }, abstract = {The establishment of monsoon climate and the consequent aridification has been one of the most important climate change episodes in the Indian subcontinent. However, little is known about how these events might have shaped the diversification patterns among the widely distributed taxa. Fan-throated lizards (FTL) (Genus: Sitana, Sarada) are widespread, diurnal and restricted to the semi-arid zones of the Indian subcontinent. We sampled FTL in 107 localities across its range. We used molecular species delimitation method and delineated 15 species including six putative species. Thirteen of them were distinguishable based on morphology but two sister species were indistinguishable and have minor overlaps in distribution. Five fossils were used to calibrate and date the phylogeny. Diversification of fan-throated lizards lineage started ~18 mya and higher lineage diversification was observed after 11 my. The initial diversification corresponds to the time when monsoon climate was established and the latter was a period of intensification of monsoon and initiation of aridification. Thirteen out of the fifteen FTL species delimited are from Peninsular India; this is probably due to the landscape heterogeneity in this region. The species poor sister genus Otocryptis is paraphyletic and probably represents relict lineages which are now confined to forested areas. Thus, the seasonality led changes in habitat, from forests to open habitats appear to have driven diversification of fan-throated lizards.}, } @article {pmid29197673, year = {2018}, author = {Copin, R and Shopsin, B and Torres, VJ}, title = {After the deluge: mining Staphylococcus aureus genomic data for clinical associations and host-pathogen interactions.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {43-50}, pmid = {29197673}, issn = {1879-0364}, support = {R01 AI099394/AI/NIAID NIH HHS/United States ; UL1 TR002489/TR/NCATS NIH HHS/United States ; R01 AI103268/AI/NIAID NIH HHS/United States ; R01 AI105129/AI/NIAID NIH HHS/United States ; HHSN272201400019C/AI/NIAID NIH HHS/United States ; }, mesh = {Computational Biology ; Databases, Genetic ; Evolution, Molecular ; *Genome, Bacterial ; Genomics ; Host-Pathogen Interactions/*genetics ; Humans ; Interspersed Repetitive Sequences ; Mutation ; Staphylococcal Infections/microbiology ; Staphylococcus aureus/*genetics ; Virulence Factors/genetics ; Whole Genome Sequencing ; }, abstract = {The genome of Staphylococcus aureus has rapidly become one the most frequently sequenced among bacteria, with more than 40000 genome sequences uploaded to public databases. Computational resources required for analysis and quality assessment have lagged behind accumulation of sequence data. Improved analytic pipelines, in combination with the development of customized S. aureus reference databases, can be used to inform S. aureus biology and potentially predict clinical outcome. Here, we review the currently available data about S. aureus genome in public databases, and discuss their potential utility for understanding S. aureus evolution. Also discussed are ways to overcome challenges to the application of whole-genome sequencing data for prevention and management of S. aureus disease.}, } @article {pmid29197672, year = {2018}, author = {Li, Y and Schroeder, JW and Simmons, LA and Biteen, JS}, title = {Visualizing bacterial DNA replication and repair with molecular resolution.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {38-45}, pmid = {29197672}, issn = {1879-0364}, support = {R01 GM107312/GM/NIGMS NIH HHS/United States ; T32 GM007544/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/genetics/ultrastructure ; *DNA Repair ; *DNA Replication ; DNA, Bacterial/ultrastructure ; Escherichia coli/genetics/ultrastructure ; Microscopy/*instrumentation/*methods ; Proteins/genetics/*ultrastructure ; }, abstract = {Although DNA replication and repair in bacteria have been extensively studied for many decades, in recent years the development of single-molecule microscopy has provided a new perspective on these fundamental processes. Because single-molecule imaging super-resolves the nanometer-scale dynamics of molecules, and because single-molecule imaging is sensitive to heterogeneities within a sample, this nanoscopic microscopy technique measures the motions, localizations, and interactions of proteins in real time without averaging ensemble observations, both in vitro and in vivo. In this Review, we provide an overview of several recent single-molecule fluorescence microscopy studies on DNA replication and repair. These experiments have shown that, in both Escherichia coli and Bacillus subtilis the DNA replication proteins are highly dynamic. In particular, even highly processive replicative DNA polymerases exchange to and from the replication fork on the scale of a few seconds. Furthermore, single-molecule investigations of the DNA mismatch repair (MMR) pathway have measured the complex interactions between MMR proteins, replication proteins, and DNA. Single-molecule imaging will continue to improve our understanding of fundamental processes in bacteria including DNA replication and repair.}, } @article {pmid29197505, year = {2018}, author = {Sinigaglia, C and Thiel, D and Hejnol, A and Houliston, E and Leclère, L}, title = {A safer, urea-based in situ hybridization method improves detection of gene expression in diverse animal species.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {15-23}, doi = {10.1016/j.ydbio.2017.11.015}, pmid = {29197505}, issn = {1095-564X}, support = {648861//European Research Council/International ; }, mesh = {Animals ; Gene Expression Profiling/*methods ; Gene Expression Regulation ; Hydrozoa/genetics/*metabolism ; In Situ Hybridization/*methods ; Species Specificity ; Urea/*chemistry ; }, abstract = {In situ hybridization is a widely employed technique allowing spatial visualization of gene expression in fixed specimens. It has greatly advanced our understanding of biological processes, including developmental regulation. In situ protocols are today routinely followed in numerous laboratories, and although details might change, they all include a hybridization step, where specific antisense RNA or DNA probes anneal to the target nucleic acid sequence. This step is generally carried out at high temperatures and in a denaturing solution, called hybridization buffer, commonly containing 50% (v/v) formamide - a hazardous chemical. When applied to the soft-bodied hydrozoan medusa Clytia hemisphaerica, we found that this traditional hybridization approach was not fully satisfactory, causing extensive deterioration of morphology and tissue texture which compromised our observation and interpretation of results. We thus tested alternative solutions for in situ detection of gene expression and, inspired by optimized protocols for Northern and Southern blot analysis, we substituted the 50% formamide with an equal volume of 8M urea solution in the hybridization buffer. Our new protocol not only yielded better morphologies and tissue consistency, but also notably improved the resolution of the signal, allowing more precise localization of gene expression and reducing aspecific staining associated with problematic areas. Given the improved results and reduced manipulation risks, we tested the urea protocol on other metazoans, two brachiopod species (Novocrania anomala and Terebratalia transversa) and the priapulid worm Priapulus caudatus, obtaining a similar reduction of aspecific probe binding. Overall, substitution of formamide by urea during in situ hybridization offers a safer alternative, potentially of widespread use in research, medical and teaching contexts. We encourage other workers to test this approach on their study organisms, and hope that they will also obtain better sample preservation, more precise expression patterns and fewer problems due to aspecific staining, as we report here for Clytia medusae and Novocrania and Terebratalia developing larvae.}, } @article {pmid29197504, year = {2018}, author = {Tahara, N and Akiyama, R and Theisen, JWM and Kawakami, H and Wong, J and Garry, DJ and Kawakami, Y}, title = {Gata6 restricts Isl1 to the posterior of nascent hindlimb buds through Isl1 cis-regulatory modules.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {74-83}, pmid = {29197504}, issn = {1095-564X}, support = {R01 AR064195/AR/NIAMS NIH HHS/United States ; R01 HL122576/HL/NHLBI NIH HHS/United States ; R21 AR063782/AR/NIAMS NIH HHS/United States ; }, mesh = {Animals ; Embryo, Mammalian/cytology/*embryology ; GATA6 Transcription Factor/genetics/*metabolism ; Gene Expression Regulation, Developmental/*physiology ; Hindlimb/cytology/*embryology ; LIM-Homeodomain Proteins/*biosynthesis/genetics ; Mice ; Mice, Transgenic ; *Models, Biological ; *Nucleotide Motifs ; Transcription Factors/*biosynthesis/genetics ; }, abstract = {Isl1 is required for two processes during hindlimb development: initiation of the processes directing hindlimb development in the lateral plate mesoderm and configuring posterior hindlimb field in the nascent hindlimb buds. During these processes, Isl1 expression is restricted to the posterior mesenchyme of hindlimb buds. How this dynamic change in Isl1 expression is regulated remains unknown. We found that two evolutionarily conserved sequences, located 3' to the Isl1 gene, regulate LacZ transgene expression in the hindlimb-forming region in mouse embryos. Both sequences contain GATA binding motifs, and expression pattern analysis identified that Gata6 is expressed in the flank and the anterior portion of nascent hindlimb buds. Recent studies have shown that conditional inactivation of Gata6 in mice causes hindlimb-specific pre-axial polydactyly, indicating a role of Gata6 in anterior-posterior patterning of hindlimbs. We studied whether Gata6 restricts Isl1 in the nascent hindlimb bud through the cis-regulatory modules. In vitro experiments demonstrate that GATA6 binds to the conserved GATA motifs in the cis-regulatory modules. GATA6 repressed expression of a luciferase reporter that contains the cis-regulatory modules by synergizing with Zfpm2. Analyses of Gata6 mutant embryos showed that ISL1 levels are higher in the anterior of nascent hindlimb buds than in wild type. Moreover, we detected a greater number of Isl1-transcribing cells in the anterior of nascent hindlimb buds in Gata6 mutants. Our results support a model in which Gata6 contributes to repression of Isl1 expression in the anterior of nascent hindlimb buds.}, } @article {pmid29196527, year = {2018}, author = {Nogales, E}, title = {Profile of Joachim Frank, Richard Henderson, and Jacques Dubochet, 2017 Nobel Laureates in Chemistry.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {441-444}, pmid = {29196527}, issn = {1091-6490}, support = {/HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Chemistry/*history ; Cryoelectron Microscopy/*history ; History, 20th Century ; History, 21st Century ; Humans ; *Nobel Prize ; }, } @article {pmid29196206, year = {2018}, author = {Priyam, M and Tripathy, M and Rai, U and Ghorai, SM}, title = {Divergence of protein sensing (TLR 4, 5) and nucleic acid sensing (TLR 3, 7) within the reptilian lineage.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {210-224}, doi = {10.1016/j.ympev.2017.11.018}, pmid = {29196206}, issn = {1095-9513}, } @article {pmid29196205, year = {2018}, author = {Medina, CD and Avila, LJ and Sites, JW and Santos, J and Morando, M}, title = {Alternative methods of phylogenetic inference for the Patagonian lizard group Liolaemus elongatus-kriegi (Iguania: Liolaemini) based on mitochondrial and nuclear markers.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {158-169}, doi = {10.1016/j.ympev.2017.11.017}, pmid = {29196205}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Cell Nucleus/*genetics ; Cytochromes b/classification/genetics/metabolism ; DNA/chemistry/isolation & purification/metabolism ; Databases, Genetic ; Lizards/*classification/genetics ; Mitochondria/*genetics ; Phylogeny ; RNA, Ribosomal/chemistry/classification/genetics ; Sequence Analysis, DNA ; }, abstract = {We present different approaches to a multi-locus phylogeny for the Liolaemus elongatus-kriegi group, including almost all species and recognized lineages. We sequenced two mitochondrial and five nuclear gene regions for 123 individuals from 35 taxa, and compared relationships resolved from concatenated and species tree methods. The L. elongatus-kriegi group was inferred as monophyletic in three of the five analyses (concatenated mitochondrial, concatenated mitochondrial + nuclear gene trees, and SVD quartet species tree). The mitochondrial gene tree resolved four haploclades, three corresponding to the previously recognized complexes: L. elongatus, L. kriegi and L. petrophilus complexes, and the L. punmahuida group. The BEAST species tree approach included the L. punmahuida group within the L. kriegi complex, but the SVD quartet method placed it as sister to the L. elongatus-kriegi group. BEAST inferred species of the L. elongatus and L. petrophilus complexes as one clade, while SVDquartet inferred these two complexes as monophyletic (although with no statistical support for the L. petrophilus complex). The species tree approach also included the L. punmahuida group as part of the L. elongatus-kriegi group. Our study provides detailed multilocus phylogenetic hypotheses for the L. elongatus-kriegi group, and we discuss possible reasons for differences in the concatenation and species tree methods.}, } @article {pmid29196204, year = {2018}, author = {Salvi, D and Perera, A and Sampaio, FL and Carranza, S and Harris, DJ}, title = {Underground cryptic speciation within the Maghreb: Multilocus phylogeography sheds light on the diversification of the checkerboard worm lizard Trogonophis wiegmanni.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {118-128}, doi = {10.1016/j.ympev.2017.11.013}, pmid = {29196204}, issn = {1095-9513}, mesh = {Africa, Northern ; Amphibian Proteins/classification/genetics/metabolism ; Animals ; Biodiversity ; Biological Evolution ; DNA, Mitochondrial/chemistry/classification/genetics ; DNA-Binding Proteins/classification/genetics/metabolism ; Lizards/*classification/genetics ; Morocco ; Phylogeny ; Phylogeography ; Pro-Opiomelanocortin/classification/genetics/metabolism ; RNA, Ribosomal/chemistry/classification/genetics ; }, abstract = {Biogeographic and evolutionary patterns in the North African portion of the Western Palaearctic are poorly known. A high fraction of undescribed diversity is expected in this region, especially in groups such as reptiles. Here we used mitochondrial (12S, 16S, cytb) and nuclear (pomc, rag2, cmos) markers and morphological data to investigate phyletic diversification and phylogeographical structure in the amphisbaenian Trogonophis wiegmanni endemic to the Maghreb. Phylogenetic and molecular dating analyses based on gene trees and species trees support three deeply divergent lineages of Pliocene origin, two in Morocco and one in central Algeria and Tunisia. Parapatry, reciprocal monophyly, high genetic divergence and limited morphological differentiation between them suggest that these lineages represent independent cryptic taxonomic units. Emerging lines of evidence from this study and from available literature on Maghreb taxa support (i) a major biogeographic break between western and eastern Maghreb and (ii) a role of the Atlas as a biogeographic divide within the western Maghreb (Morocco). The origin of these biogeographic units is probably associated with the evolutionary events prompted by the Late Miocene palaeogeographic setting and later by Plio-Pleistocene climatic changes and their interplay with prominent orographic barriers within North Africa.}, } @article {pmid29195693, year = {2018}, author = {}, title = {Why is genetics education so important?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {1-4}, doi = {10.1016/j.tig.2017.10.006}, pmid = {29195693}, issn = {0168-9525}, mesh = {Biology/education ; Genetics/*education ; Humans ; }, } @article {pmid29195049, year = {2018}, author = {Kato, M and McKnight, SL}, title = {A Solid-State Conceptualization of Information Transfer from Gene to Message to Protein.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {351-390}, doi = {10.1146/annurev-biochem-061516-044700}, pmid = {29195049}, issn = {1545-4509}, support = {R01 GM107623/GM/NIGMS NIH HHS/United States ; U01 GM107623/GM/NIGMS NIH HHS/United States ; }, abstract = {In this review, we describe speculative ideas and early stage research concerning the flow of genetic information from the nuclear residence of genes to the disparate, cytoplasmic sites of protein synthesis. We propose that this process of information transfer is meticulously guided by transient structures formed from protein segments of low sequence complexity/intrinsic disorder. These low complexity domains are ubiquitously associated with regulatory proteins that control gene expression and RNA biogenesis, but they are also found in the central channel of nuclear pores, the nexus points of intermediate filament assembly, and the locations of action of other well-studied cellular proteins and pathways. Upon being organized into localized cellular positions via mechanisms utilizing properly folded protein domains, thereby facilitating elevated local concentration, certain low complexity domains adopt cross-β interactions that are both structurally specific and labile to disassembly. These weakly tethered assemblies, we propose, are built to relay the passage of genetic information from one site to another within a cell, ensuring that the process is of extreme fidelity.}, } @article {pmid29195004, year = {2018}, author = {Yi, Y and Frenzel, E and Spoelder, J and Elzenga, JTM and van Elsas, JD and Kuipers, OP}, title = {Optimized fluorescent proteins for the rhizosphere-associated bacterium Bacillus mycoides with endophytic and biocontrol agent potential.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {57-74}, doi = {10.1111/1758-2229.12607}, pmid = {29195004}, issn = {1758-2229}, abstract = {Tracking of fluorescent protein (FP)-labelled rhizobacteria is a key prerequisite to gain insights into plant-bacteria interaction mechanisms. However, the performance of FPs mostly has to be optimized for the bacterial host and for the environment of intended application. We report on the construction of mutational libraries of the superfolder green fluorescent protein sfGFP and the red fluorescent protein mKate2 in the bacterium B. mycoides, which next to its potential as plant-biocontrol agent occasionally enters an endophytic lifestyle. By fluorescence-activated cell sorting and comparison of signal intensities at the colony and single-cell level, the variants sfGFP(SPS6) and mKate (KPS12) with significantly increased brightness were isolated. Their high applicability for plant-bacteria interaction studies was shown by confocal laser scanning microscopy tracking of FP-tagged B. mycoides strains after inoculation to Chinese cabbage plants in a hydroponic system. During the process of colonization, strain EC18 rapidly attached to plant roots and formed a multicellular matrix, especially at the branching regions of the root hair, which probably constitute entrance sites to establish an endophytic lifestyle. The universal applicability of the novels FPs was proven by expression from a weak promoter, dual-labelling of B. mycoides, and by excellent expression and detectability in additional soil- and rhizosphere-associated Bacillus species.}, } @article {pmid29194987, year = {2018}, author = {Steinert, G and Gutleben, J and Atikana, A and Wijffels, RH and Smidt, H and Sipkema, D}, title = {Coexistence of poribacterial phylotypes among geographically widespread and phylogenetically divergent sponge hosts.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {80-91}, doi = {10.1111/1758-2229.12609}, pmid = {29194987}, issn = {1758-2229}, abstract = {Marine sponges are benthic 'filter-feeding' invertebrates that can host dense and diverse bacterial, archaeal and eukaryotic communities. Due to the finding of several genes encoding symbiosis factors, such as adhesins, ankyrin repeats and tetratricopeptide repeats, the candidate phylum 'Poribacteria' is considered as a promising model microorganism for studying the origin of host-symbiont interactions in sponges. However, relatively little is known about its global diversity and phylogenetic distribution among different sponge hosts. Therefore, in this study we investigated phylogenetic relationships among poribacterial phylotypes and generated a phylogenetic network to examine the distribution and intraspecific diversity of the phylotypes between phylogenetically divergent host-sponges at a global scale. For this study 361 poribacterial 16S rRNA gene sequences obtained by Sanger sequencing from 15 different countries and 8 marine regions were gathered. We could demonstrate that the candidate phylum 'Poribacteria' is composed of diverse phylotypes, which are distributed among a wide range of phylogenetically divergent sponge hosts. The current phylogenetic analyses found neither conclusive evidence for co-speciation with its hosts, nor biogeographical correlation. Moreover, we identified a novel poribacterial clade, which might represent a link between the previously established four 'Poribacteria' clades.}, } @article {pmid29194984, year = {2018}, author = {Aučynaitė, A and Rutkienė, R and Gasparavičiūtė, R and Meškys, R and Urbonavičius, J}, title = {A gene encoding a DUF523 domain protein is involved in the conversion of 2-thiouracil into uracil.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {49-56}, doi = {10.1111/1758-2229.12605}, pmid = {29194984}, issn = {1758-2229}, abstract = {Modified nucleotides are present in many RNA species in all Domains of Life. While the biosynthetic pathways of such nucleotides are well studied, much less is known about the degradation of RNAs and the return to the metabolism of modified nucleotides, their respective nucleosides or heterocyclic bases. Using an E. coli uracil auxotroph, we screened the metagenomic libraries for genes, which would allow the conversion of 2-thiouracil to uracil and thereby lead to the growth on a defined synthetic medium. We show that a gene encoding a protein consisting of previously uncharacterized Domain of Unknown Function 523 (DUF523) is responsible for such phenotype. We have purified this recombinant protein and demonstrated that it contains a FeS cluster. The substitution of cysteines, which have been predicted to form such clusters, with alanines abolished the growth phenotype. We conclude that DUF523 is involved in the conversion of 2-thiouracil into uracil in vivo.}, } @article {pmid29194980, year = {2018}, author = {Tanner, K and Martí, JM and Belliure, J and Fernández-Méndez, M and Molina-Menor, E and Peretó, J and Porcar, M}, title = {Polar solar panels: Arctic and Antarctic microbiomes display similar taxonomic profiles.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {75-79}, doi = {10.1111/1758-2229.12608}, pmid = {29194980}, issn = {1758-2229}, abstract = {Solar panels located on high (Arctic and Antarctic) latitudes combine the harshness of the climate with that of the solar exposure. We report here that these polar solar panels are inhabited by similar microbial communities in taxonomic terms, dominated by Hymenobacter spp., Sphingomonas spp. and Ascomycota. Our results suggest that solar panels, even on high latitudes, can shape a microbial ecosystem adapted to irradiation and desiccation.}, } @article {pmid29194953, year = {2018}, author = {Cordero, GA and Telemeco, RS and Gangloff, EJ}, title = {Reptile embryos are not capable of behavioral thermoregulation in the egg.}, journal = {Evolution & development}, volume = {20}, number = {1}, pages = {40-47}, doi = {10.1111/ede.12244}, pmid = {29194953}, issn = {1525-142X}, mesh = {Animals ; Behavior, Animal ; *Body Temperature Regulation ; Embryo, Nonmammalian/cytology/*physiology ; Embryonic Development ; Ovum/cytology/*physiology ; Reptiles/*embryology/*physiology ; Temperature ; }, abstract = {Reptile embryos have recently been observed moving within the egg in response to temperature, raising the exciting possibility that embryos might behaviorally thermoregulate analogous to adults. However, the conjecture that reptile embryos have ample opportunity and capacity to adaptively control their body temperature warrants further discussion. Using turtles as a model, we discuss the spatiotemporal constraints to movement in reptile embryos. We demonstrate that, as embryos grow, the internal egg space rapidly diminishes such that the temporal window for appreciable displacement is confined to stages that feature incomplete neuromuscular differentiation. During this time, muscles are insufficiently developed to actively and consistently control movement. These constraints are well illustrated by the Chinese softshelled turtle (Pelodiscus sinensis), the first reptile reported to behaviorally thermoregulate. Furthermore, sporadic embryo activity peaks after the temperature-sensitive period in species with temperature-dependent sex determination, thus nullifying the opportunity for embryos to exhibit control over this important phenotype. These embryonic constraints add to previously-identified environmental constraints on behavioral thermoregulation by reptile embryos. We discuss alternative hypotheses to explain previously reported patterns of behavioral thermoregulation. Based on a holistic consideration of embryonic limitations, we conclude that reptile embryos are generally unable to adaptively behaviorally thermoregulate within the egg.}, } @article {pmid29194950, year = {2018}, author = {McMillan, LJ and Hwang, S and Farah, RE and Koh, J and Chen, S and Maupin-Furlow, JA}, title = {Multiplex quantitative SILAC for analysis of archaeal proteomes: a case study of oxidative stress responses.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {385-401}, pmid = {29194950}, issn = {1462-2920}, support = {R01 GM057498/GM/NIGMS NIH HHS/United States ; }, abstract = {Stable isotope labelling of amino acids in cell culture (SILAC) is a quantitative proteomic method that can illuminate new pathways used by cells to adapt to different lifestyles and niches. Archaea, while thriving in extreme environments and accounting for ∼20%-40% of the Earth's biomass, have not been analyzed with the full potential of SILAC. Here, we report SILAC for quantitative comparison of archaeal proteomes, using Haloferax volcanii as a model. A double auxotroph was generated that allowed for complete incorporation of 13 C/15 N-lysine and 13 C-arginine such that each peptide derived from trypsin digestion was labelled. This strain was found amenable to multiplex SILAC by case study of responses to oxidative stress by hypochlorite. A total of 2565 proteins was identified by LC-MS/MS analysis (q-value ≤ 0.01) that accounted for 64% of the theoretical proteome. Of these, 176 proteins were altered at least 1.5-fold (p-value < 0.05) in abundance during hypochlorite stress. Many of the differential proteins were of unknown function. Those of known function included transcription factor homologs related to oxidative stress by 3D-homology modelling and orthologous group comparisons. Thus, SILAC is found to be an ideal method for quantitative proteomics of archaea that holds promise to unravel gene function.}, } @article {pmid29194931, year = {2018}, author = {Feng, J and Li, B and Jiang, X and Yang, Y and Wells, GF and Zhang, T and Li, X}, title = {Antibiotic resistome in a large-scale healthy human gut microbiota deciphered by metagenomic and network analyses.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {355-368}, doi = {10.1111/1462-2920.14009}, pmid = {29194931}, issn = {1462-2920}, abstract = {The human gut microbiota is an important reservoir of antibiotic resistance genes (ARGs). A metagenomic approach and network analysis were used to establish a comprehensive antibiotic resistome catalog and to obtain co-occurrence patterns between ARGs and microbial taxa in fecal samples from 180 healthy individuals from 11 different countries. In total, 507 ARG subtypes belonging to 20 ARG types were detected with abundances ranging from 7.12 × 10-7 to 2.72 × 10-1 copy of ARG/copy of 16S-rRNA gene. Tetracycline, multidrug, macrolide-lincosamide-streptogramin, bacitracin, vancomycin, beta-lactam and aminoglycoside resistance genes were the top seven most abundant ARG types. The multidrug ABC transporter, aadE, bacA, acrB, tetM, tetW, vanR and vanS were shared by all 180 individuals, suggesting their common occurrence in the human gut. Compared to populations from the other 10 countries, the Chinese population harboured the most abundant ARGs. Moreover, LEfSe analysis suggested that the MLS resistance type and its subtype 'ermF' were representative ARGs of the Chinese population. Antibiotic inactivation, antibiotic target alteration and antibiotic efflux were the dominant resistance mechanism categories in all populations. Procrustes analysis revealed that microbial phylogeny structured the antibiotic resistome. Co-occurrence patterns obtained via network analysis implied that 12 species might be potential hosts of 58 ARG subtypes.}, } @article {pmid29194930, year = {2018}, author = {Martínez-Pérez, C and Mohr, W and Schwedt, A and Dürschlag, J and Callbeck, CM and Schunck, H and Dekaezemacker, J and Buckner, CRT and Lavik, G and Fuchs, BM and Kuypers, MMM}, title = {Metabolic versatility of a novel N2 -fixing Alphaproteobacterium isolated from a marine oxygen minimum zone.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {755-768}, doi = {10.1111/1462-2920.14008}, pmid = {29194930}, issn = {1462-2920}, abstract = {The N2 -fixing (diazotrophic) community in marine ecosystems is dominated by non-cyanobacterial microorganisms. Yet, very little is known about their identity, function and ecological relevance due to a lack of cultured representatives. Here we report a novel heterotrophic diazotroph isolated from the oxygen minimum zone (OMZ) off Peru. The new species belongs to the genus Sagittula (Rhodobacteraceae, Alphaproteobacteria) and its capability to fix N2 was confirmed in laboratory experiments. Genome sequencing revealed that it is a strict heterotroph with a high versatility in substrate utilization and energy acquisition mechanisms. Pathways for sulfide oxidation and nitrite reduction to nitrous oxide are encoded in the genome and might explain the presence throughout the Peruvian OMZ. The genome further indicates that this novel organism could be in direct interaction with other microbes or particles. NanoSIMS analyses were used to compare the metabolic potential of S. castanea with single-cell activity in situ; however, N2 fixation by this diazotroph could not be detected at the isolation site. While the biogeochemical impact of S. castanea is yet to be resolved, its abundance and widespread distribution suggests that its potential to contribute to the marine N input could be significant at a larger geographical scale.}, } @article {pmid29194923, year = {2018}, author = {Taubert, M and Stöckel, S and Geesink, P and Girnus, S and Jehmlich, N and von Bergen, M and Rösch, P and Popp, J and Küsel, K}, title = {Tracking active groundwater microbes with D2 O labelling to understand their ecosystem function.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {369-384}, doi = {10.1111/1462-2920.14010}, pmid = {29194923}, issn = {1462-2920}, abstract = {Microbial activity is key in understanding the contribution of microbial communities to ecosystem functions. Metabolic labelling with heavy water (D2 O) leads to the formation of carbon-deuterium bonds in active microorganisms. We illustrated how D2 O labelling allows monitoring of metabolic activity combined with a functional characterization of active populations in complex microbial communities. First, we demonstrated by single cell Raman microspectroscopy that all measured bacterial cells from groundwater isolates growing in complex medium with D2 O were labelled. Next, we conducted a labelling approach with the total groundwater microbiome in D2 O amended microcosms. Deuterium was incorporated in most measured cells, indicating metabolic activity in the oligotrophic groundwater. Moreover, we spiked the groundwater microbiome with organic model compounds. We discovered that heterotrophs assimilating veratric acid, a lignin derivative, showed higher labelling than heterotrophs assimilating methylamine, a degradation product of biomass. This difference can be explained by dilution of the deuterium through hydrogen from the organic compounds. Metaproteomics identified Sphingomonadaceae and Microbacteriaceae as key players in veratric acid degradation, and the metabolic pathways employed. Methylamine, in contrast, stimulated various proteobacterial genera. We propose this combined approach of Raman microspectroscopy and metaproteomics for elucidating the complex metabolic response of microbial populations to different stimuli.}, } @article {pmid29194919, year = {2018}, author = {Lavy, A and Keren, R and Yu, K and Thomas, BC and Alvarez-Cohen, L and Banfield, JF and Ilan, M}, title = {A novel Chromatiales bacterium is a potential sulfide oxidizer in multiple orders of marine sponges.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {800-814}, pmid = {29194919}, issn = {1462-2920}, support = {P42 ES004705/ES/NIEHS NIH HHS/United States ; }, abstract = {Sponges are benthic filter feeders that play pivotal roles in coupling benthic-pelagic processes in the oceans that involve transformation of dissolved and particulate organic carbon and nitrogen into biomass. While the contribution of sponge holobionts to the nitrogen cycle has been recognized in past years, their importance in the sulfur cycle, both oceanic and physiological, has only recently gained attention. Sponges in general, and Theonella swinhoei in particular, harbour a multitude of associated microorganisms that could affect sulfur cycling within the holobiont. We reconstructed the genome of a Chromatiales (class Gammaproteobacteria) bacterium from a metagenomic sequence dataset of a T. swinhoei-associated microbial community. This relatively abundant bacterium has the metabolic capability to oxidize sulfide yet displays reduced metabolic potential suggestive of its lifestyle as an obligatory symbiont. This bacterium was detected in multiple sponge orders, according to similarities in key genes such as 16S rRNA and polyketide synthase genes. Due to its sulfide oxidation metabolism and occurrence in many members of the Porifera phylum, we suggest naming the newly described taxon Candidatus Porisulfidus.}, } @article {pmid29194914, year = {2018}, author = {Troselj, V and Cao, P and Wall, D}, title = {Cell-cell recognition and social networking in bacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {3}, pages = {923-933}, pmid = {29194914}, issn = {1462-2920}, support = {P20 GM103432/GM/NIGMS NIH HHS/United States ; R01 GM101449/GM/NIGMS NIH HHS/United States ; }, abstract = {The ability to recognize self and to recognize partnering cells allows microorganisms to build social networks that perform functions beyond the capabilities of the individual. In bacteria, recognition typically involves genetic determinants that provide cell surface receptors or diffusible signalling chemicals to identify proximal cells at the molecular level that can participate in cooperative processes. Social networks also rely on discriminating mechanisms to exclude competing cells from joining and exploiting their groups. In addition to their appropriate genotypes, cell-cell recognition also requires compatible phenotypes, which vary according to environmental cues or exposures as well as stochastic processes that lead to heterogeneity and potential disharmony in the population. Understanding how bacteria identify their social partners and how they synchronize their behaviours to conduct multicellular functions is an expanding field of research. Here, we review recent progress in the field and contrast the various strategies used in recognition and behavioural networking.}, } @article {pmid29194913, year = {2018}, author = {Kelly, S and Sullivan, JT and Kawaharada, Y and Radutoiu, S and Ronson, CW and Stougaard, J}, title = {Regulation of Nod factor biosynthesis by alternative NodD proteins at distinct stages of symbiosis provides additional compatibility scrutiny.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {97-110}, doi = {10.1111/1462-2920.14006}, pmid = {29194913}, issn = {1462-2920}, abstract = {The Lotus japonicus symbiont Mesorhizobium loti R7A encodes two copies of nodD and here we identify striking differences in Nod factor biosynthesis gene induction by NodD1 and NodD2 both in vitro and in planta. We demonstrate that induction of Nod factor biosynthesis genes is preferentially controlled by NodD1 and NodD2 at specific stages of symbiotic infection. NodD2 is primarily responsible for induction in the rhizosphere and within nodules, while NodD1 is primarily responsible for induction within root hair infection threads. nodD1 and nodD2 mutants showed significant symbiotic phenotypes and competition studies establish that nodD1 and nodD2 mutants were severely outcompeted by wild-type R7A, indicating that both proteins are required for proficient symbiotic infection. These results suggest preferential activation of NodD1 and NodD2 by different inducing compounds produced at defined stages of symbiotic infection. We identified Lotus chalcone isomerase CHI4 as a root hair induced candidate involved in the biosynthesis of an inducer compound that may be preferentially recognized by NodD1 within root hair infection threads. We propose an alternative explanation for the function of multiple copies of nodD that provides the host plant with another level of compatibility scrutiny at the stage of infection thread development.}, } @article {pmid29194907, year = {2018}, author = {Kaur, A and Hernandez-Fernaud, JR and Aguilo-Ferretjans, MDM and Wellington, EM and Christie-Oleza, JA}, title = {100 Days of marine Synechococcus-Ruegeria pomeroyi interaction: A detailed analysis of the exoproteome.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {785-799}, pmid = {29194907}, issn = {1462-2920}, support = {BB/M017982/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Marine phototroph and heterotroph interactions are vital in maintaining the nutrient balance in the oceans as essential nutrients need to be rapidly cycled before sinking to aphotic layers. The aim of this study was to highlight the molecular mechanisms that drive these interactions. For this, we generated a detailed exoproteomic time-course analysis of a 100-day co-culture between the model marine picocyanobacterium Synechococcus sp. WH7803 and the Roseobacter strain Ruegeria pomeroyi DSS-3, both in nutrient-enriched and natural oligotrophic seawater. The proteomic data showed a transition between the initial growth phase and stable-state phase that, in the case of the heterotroph, was caused by a switch in motility attributed to organic matter availability. The phototroph adapted to seawater oligotrophy by reducing its selective leakiness, increasing the acquisition of essential nutrients and secreting conserved proteins of unknown function. We also report a surprisingly high abundance of extracellular superoxide dismutase produced by Synechococcus and a dynamic secretion of potential hydrolytic enzyme candidates used by the heterotroph to cleave organic groups and hydrolase polymeric organic matter produced by the cyanobacterium. The time course dataset we present here will become a reference for understanding the molecular processes underpinning marine phototroph-heterotroph interactions.}, } @article {pmid29194863, year = {2018}, author = {DeFilippo, LB and Schindler, DE and Carter, JL and Walsworth, TE and Cline, TJ and Larson, WA and Buehrens, T}, title = {Associations of stream geomorphic conditions and prevalence of alternative reproductive tactics among sockeye salmon populations.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {239-253}, doi = {10.1111/jeb.13217}, pmid = {29194863}, issn = {1420-9101}, abstract = {In many species, males may exhibit alternative life histories to circumvent the costs of intrasexual competition and female courtship. While the evolution and underlying genetic and physiological mechanisms behind alternative reproductive tactics are well studied, there has been less consideration of the ecological factors that regulate their prevalence. Here, we examine six decades of age composition records from thirty-six populations of sockeye salmon (Oncorhynchus nerka) to quantify associations between spawning habitat characteristics and the prevalence of precocious sneakers known as 'jacks'. Jack prevalence was independent of neutral genetic structure among stream populations, but varied among habitat types and as a function of continuous geomorphic characteristics. Jacks were more common in streams relative to beaches and rivers, and their prevalence was negatively associated with stream width, depth, elevation, slope and area, but positively related to bank cover. Behavioural observations showed that jacks made greater use of banks, wood and shallows than guard males, indicating that their reproductive success depends on the availability of such refuges. Our results emphasize the role of the physical habitat in shaping reproductive tactic frequencies among populations, likely through local adaptation in response to variable fitness expectations under different geomorphic conditions.}, } @article {pmid29194840, year = {2018}, author = {Brown, CR and Brown, MB}, title = {Parasites favour intermediate nestling mass and brood size in cliff swallows.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {254-266}, pmid = {29194840}, issn = {1420-9101}, support = {R01 AI057569/AI/NIAID NIH HHS/United States ; }, abstract = {A challenge of life-history theory is to explain why animal body size does not continue to increase, given various advantages of larger size. In birds, body size of nestlings and the number of nestlings produced (brood size) have occasionally been shown to be constrained by higher predation on larger nestlings and those from larger broods. Parasites also are known to have strong effects on life-history traits in birds, but whether parasitism can be a driver for stabilizing selection on nestling body size or brood size is unknown. We studied patterns of first-year survival in cliff swallows (Petrochelidon pyrrhonota) in western Nebraska in relation to brood size and nestling body mass in nests under natural conditions and in those in which hematophagous ectoparasites had been removed by fumigation. Birds from parasitized nests showed highest first-year survival at the most common, intermediate brood-size and nestling-mass categories, but cliff swallows from nonparasitized nests had highest survival at the heaviest nestling masses and no relationship with brood size. A survival analysis suggested stabilizing selection on brood size and nestling mass in the presence (but not in the absence) of parasites. Parasites apparently favour intermediate offspring size and number in cliff swallows and produce the observed distributions of these traits, although the mechanisms are unclear. Our results emphasize the importance of parasites in life-history evolution.}, } @article {pmid29194826, year = {2018}, author = {Gruber, J and Cunningham, GD and While, GM and Wapstra, E}, title = {Disentangling sex allocation in a viviparous reptile with temperature-dependent sex determination: a multifactorial approach.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {267-276}, doi = {10.1111/jeb.13219}, pmid = {29194826}, issn = {1420-9101}, abstract = {Females are predicted to alter sex allocation when ecological, physiological and behavioural variables have different consequences on the fitness of male and female offspring. Traditionally, tests of sex allocation have examined single causative factors, often ignoring possible interactions between multiple factors. Here, we used a multifactorial approach to examine sex allocation in the viviparous skink, Niveoscincus ocellatus. We integrated a 16-year observational field study with a manipulative laboratory experiment to explore whether the effects of the maternal thermal environment interact with the resources available to females for reproduction to affect sex allocation decisions. We found strong effects of temperature on sex allocation in the field, with females born in warm conditions and males in cold conditions; however, this was not replicated in the laboratory. In contrast, we found no effect of female resource availability on sex allocation, either independently, or in interaction with temperature. These results corresponded with an overall lack of an effect of resource availability on any of the life history traits that we predicted would mediate the benefits of differential sex allocation in this system, suggesting that selection for sex allocation in response to resource availability may be relatively weak. Combined, these results suggest that temperature may be the predominant factor driving sex allocation in this system.}, } @article {pmid29192334, year = {2018}, author = {Literman, R and Burrett, A and Bista, B and Valenzuela, N}, title = {Putative Independent Evolutionary Reversals from Genotypic to Temperature-Dependent Sex Determination are Associated with Accelerated Evolution of Sex-Determining Genes in Turtles.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {11-26}, pmid = {29192334}, issn = {1432-1432}, support = {1310793//Division of Environmental Biology/ ; 1244355//Division of Molecular and Cellular Biosciences/ ; 1555999//Division of Integrative Organismal Systems/ ; }, abstract = {The evolutionary lability of sex-determining mechanisms across the tree of life is well recognized, yet the extent of molecular changes that accompany these repeated transitions remain obscure. Most turtles retain the ancestral temperature-dependent sex determination (TSD) from which multiple transitions to genotypic sex determination (GSD) occurred independently, and two contrasting hypotheses posit the existence or absence of reversals back to TSD. Here we examined the molecular evolution of the coding regions of a set of gene regulators involved in gonadal development in turtles and several other vertebrates. We found slower molecular evolution in turtles and crocodilians compared to other vertebrates, but an acceleration in Trionychia turtles and at some phylogenetic branches demarcating major taxonomic diversification events. Of all gene classes examined, hormone signaling genes, and Srd5a1 in particular, evolve faster in many lineages and especially in turtles. Our data show that sex-linked genes do not follow a ubiquitous nor uniform pattern of molecular evolution. We then evaluated turtle nucleotide and protein evolution under two evolutionary hypotheses with or without GSD-to-TSD reversals, and found that when GSD-to-TSD reversals are considered, all transitional branches irrespective of direction, exhibit accelerated molecular evolution of nucleotide sequences, while GSD-to-TSD transitional branches also show acceleration in protein evolution. Significant changes in predicted secondary structure that may affect protein function were identified in three genes that exhibited hastened evolution in turtles compared to other vertebrates or in transitional versus non-transitional branches within turtles, rendering them candidates for a key role during SDM evolution in turtles.}, } @article {pmid29191558, year = {2018}, author = {Kaminsky, R}, title = {Where Is the Breakthrough Innovation for Parasite Control?.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {99-101}, doi = {10.1016/j.pt.2017.11.004}, pmid = {29191558}, issn = {1471-5007}, mesh = {Animals ; Antiparasitic Agents/standards/therapeutic use ; *Drug Resistance ; Humans ; Parasitic Diseases/drug therapy/*prevention & control ; Research/standards/trends ; }, abstract = {The need to improve parasite control to overcome drug-resistant parasite populations, and to improve compliance by more convenient drug application methods, is evident. While a number of incremental stepwise improvements are visible, the big disruptive innovation, an iPhone-equivalent breakthrough, has been hard to find. Why?}, } @article {pmid29191415, year = {2018}, author = {Bibi, F and Pante, M and Souron, A and Stewart, K and Varela, S and Werdelin, L and Boisserie, JR and Fortelius, M and Hlusko, L and Njau, J and de la Torre, I}, title = {Paleoecology of the Serengeti during the Oldowan-Acheulean transition at Olduvai Gorge, Tanzania: The mammal and fish evidence.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {48-75}, doi = {10.1016/j.jhevol.2017.10.009}, pmid = {29191415}, issn = {1095-8606}, abstract = {Eight years of excavation work by the Olduvai Geochronology and Archaeology Project (OGAP) has produced a rich vertebrate fauna from several sites within Bed II, Olduvai Gorge, Tanzania. Study of these as well as recently re-organized collections from Mary Leakey's 1972 HWK EE excavations here provides a synthetic view of the faunal community of Olduvai during Middle Bed II at ∼1.7-1.4 Ma, an interval that captures the local transition from Oldowan to Acheulean technology. We expand the faunal list for this interval, name a new bovid species, clarify the evolution of several mammalian lineages, and record new local first and last appearances. Compositions of the fish and large mammal assemblages support previous indications for the dominance of open and seasonal grassland habitats at the margins of an alkaline lake. Fish diversity is low and dominated by cichlids, which indicates strongly saline conditions. The taphonomy of the fish assemblages supports reconstructions of fluctuating lake levels with mass die-offs in evaporating pools. The mammals are dominated by grazing bovids and equids. Habitats remained consistently dry and open throughout the entire Bed II sequence, with no major turnover or paleoecological changes taking place. Rather, wooded and wet habitats had already given way to drier and more open habitats by the top of Bed I, at 1.85-1.80 Ma. This ecological change is close to the age of the Oldowan-Acheulean transition in Kenya and Ethiopia, but precedes the local transition in Middle Bed II. The Middle Bed II large mammal community is much richer in species and includes a much larger number of large-bodied species (>300 kg) than the modern Serengeti. This reflects the severity of Pleistocene extinctions on African large mammals, with the loss of large species fitting a pattern typical of defaunation or 'downsizing' by human disturbance. However, trophic network (food web) analyses show that the Middle Bed II community was robust, and comparisons with the Serengeti community indicate that the fundamental structure of food webs remained intact despite Pleistocene extinctions. The presence of a generalized meat-eating hominin in the Middle Bed II community would have increased competition among carnivores and vulnerability among herbivores, but the high generality and interconnectedness of the Middle Bed II food web suggests this community was buffered against extinctions caused by trophic interactions.}, } @article {pmid29191399, year = {2018}, author = {Nai, C and Meyer, V}, title = {From Axenic to Mixed Cultures: Technological Advances Accelerating a Paradigm Shift in Microbiology.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {538-554}, doi = {10.1016/j.tim.2017.11.004}, pmid = {29191399}, issn = {1878-4380}, abstract = {Since the onset of microbiology in the late 19th century, scientists have been growing microorganisms almost exclusively as pure cultures, resulting in a limited and biased view of the microbial world. Only a paradigm shift in cultivation techniques - from axenic to mixed cultures - can allow a full comprehension of the (chemical) communication of microorganisms, with profound consequences for natural product discovery, microbial ecology, symbiosis, and pathogenesis, to name a few areas. Three main technical advances during the last decade are fueling the realization of this revolution in microbiology: microfluidics, next-generation 3D-bioprinting, and single-cell metabolomics. These technological advances can be implemented for large-scale, systematic cocultivation studies involving three or more microorganisms. In this review, we present recent trends in microbiology tools and discuss how these can be employed to decode the chemical language that microorganisms use to communicate.}, } @article {pmid29191398, year = {2018}, author = {Bell, G and MacLean, C}, title = {The Search for 'Evolution-Proof' Antibiotics.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {471-483}, doi = {10.1016/j.tim.2017.11.005}, pmid = {29191398}, issn = {1878-4380}, support = {106918/Z/15/Z//Wellcome Trust/United Kingdom ; }, abstract = {The effectiveness of antibiotics has been widely compromised by the evolution of resistance among pathogenic bacteria. It would be restored by the development of antibiotics to which bacteria cannot evolve resistance. We first discuss two kinds of 'evolution-proof' antibiotic. The first comprises literally evolution-proof antibiotics to which bacteria cannot become resistant by mutation or horizontal gene transfer. The second category comprises agents to which resistance may arise, but so rarely that it does not become epidemic. The likelihood that resistance to a novel agent will spread is evaluated here by a simple model that includes biological and therapeutic parameters governing the evolution of resistance within hosts and the transmission of resistant strains between hosts. This model leads to the conclusion that epidemic spread is unlikely if the frequency of mutations that confer resistance falls below a defined minimum value, and it identifies potential targets for intervention to prevent the evolution of resistance. Whether or not evolution-proof antibiotics are ever found, searching for them is likely to improve the deployment of new and existing agents by advancing our understanding of how resistance evolves.}, } @article {pmid29190491, year = {2018}, author = {Gago, G and Diacovich, L and Gramajo, H}, title = {Lipid metabolism and its implication in mycobacteria-host interaction.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {36-42}, pmid = {29190491}, issn = {1879-0364}, support = {R01 AI095183/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Cell Wall/chemistry/metabolism ; Homeostasis ; Host-Pathogen Interactions/genetics/immunology/*physiology ; Humans ; Lipid Metabolism/genetics/*physiology ; Macrophages/immunology/microbiology ; Metabolic Networks and Pathways/physiology ; Mice ; Mycobacterium tuberculosis/chemistry/immunology/*metabolism/pathogenicity ; Tuberculosis/immunology/microbiology/therapy ; }, abstract = {The complex lipids present in the cell wall of Mycobacterium tuberculosis (Mtb) act as major effector molecules that actively interact with the host, modulating its metabolism and stimulating the immune response, which in turn affects the physiology of both, the host cell and the bacilli. Lipids from the host are also nutrient sources for the pathogen and define the fate of the infection by modulating lipid homeostasis. Although new technologies and experimental models of infection have greatly helped understanding the different aspects of the host-pathogen interactions at the lipid level, the impact of this interaction in the Mtb lipid regulation is still incipient, mainly because of the low background knowledge in this area of research.}, } @article {pmid29190490, year = {2018}, author = {Personnic, N and Striednig, B and Hilbi, H}, title = {Legionella quorum sensing and its role in pathogen-host interactions.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {29-35}, doi = {10.1016/j.mib.2017.11.010}, pmid = {29190490}, issn = {1879-0364}, mesh = {4-Butyrolactone/analogs & derivatives/metabolism ; Bacterial Proteins/genetics/metabolism ; Cell Movement ; *Gene Expression Regulation, Bacterial ; Host-Pathogen Interactions/genetics/*physiology ; Humans ; Legionella ; Legionella pneumophila/genetics/metabolism/*pathogenicity ; Legionnaires' Disease/microbiology ; *Quorum Sensing ; Signal Transduction ; Virulence/genetics ; }, abstract = {Legionella pneumophila is a water-borne opportunistic pathogen causing a life-threatening pneumonia called 'Legionnaires' disease'. The Legionella quorum sensing (Lqs) system produces and responds to the α-hydroxyketone signaling molecule 3-hydroxypentadecane-4-one (Legionella autoinducer-1, LAI-1). The Lqs system controls the switch between the replicative/non-virulent and the transmissive/virulent phase of L. pneumophila, and it is a major regulator of natural competence, motility and virulence of the pathogen. Yet, beyond gene regulation, LAI-1 also directly affects pathogen-host interactions, since the signaling molecule modulates the migration of eukaryotic cells. Genes encoding Lqs homologues are present in many environmental bacteria, suggesting that α-hydroxyketone signaling is widely used for inter-bacterial as well as inter-kingdom signaling. In this review we summarize recent advances on the characterization of the Lqs system and its role in L. pneumophila-host cell interactions.}, } @article {pmid29189942, year = {2018}, author = {Bayat, H and Modarressi, MH and Rahimpour, A}, title = {The Conspicuity of CRISPR-Cpf1 System as a Significant Breakthrough in Genome Editing.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {107-115}, pmid = {29189942}, issn = {1432-0991}, mesh = {Bacteria/enzymology/*genetics/metabolism ; Bacterial Proteins/genetics/*metabolism ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Endonucleases/genetics/*metabolism ; *Gene Editing ; }, abstract = {Clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein (Cas) is a microbial adaptive immune system. CRISPR-Cas systems are classified into two main classes and six types. Cpf1 is a putative type V (class II) CRISPR effector, which has revolutionized the genome editing approaches through multiple distinct features such as using T-rich protospacer-adjacent motif, applying a short guide RNA lacking trans-activating crRNA, introducing a staggered double-strand break, and possessing RNA processing activity in addition to DNA nuclease activity. In the present review, we attempt to highlight most recent advances in CRISPR-Cpf1 (CRISPR-Cas12a) system in particular, considering ground expeditions of the nature and the biology of this system, introducing novel Cpf1 variants that have broadened the versatility and feasibility of CRISPR-Cpf1 system, and lastly the great impact of the CRISPR-Cpf1 system on the manipulation of the genome of prokaryotic, mammalian, and plant models is summarized. With regard to recent developments in utilizing the CRISPR-Cpf1 system in genome editing of various organisms, it can be concluded with confidence that this system is a reliable molecular toolbox of genome editing approaches.}, } @article {pmid29189888, year = {2018}, author = {Rivas, M and Becerra, A and Lazcano, A}, title = {On the Early Evolution of Catabolic Pathways: A Comparative Genomics Approach. I. The Cases of Glucose, Ribose, and the Nucleobases Catabolic Routes.}, journal = {Journal of molecular evolution}, volume = {86}, number = {1}, pages = {27-46}, pmid = {29189888}, issn = {1432-1432}, support = {255708//CONACYT/ ; IN223916//PAPIIT-UNAM/ ; }, abstract = {Compared with the large corpus of published work devoted to the study of the origin and early development of anabolism, little attention has been given to the discussion of the early evolution of catabolism in spite of its significance. In the present study, we have used comparative genomics to explore the evolution and phylogenetic distribution of the enzymes that catalyze the extant catabolic pathways of the monosaccharides glucose and ribose, as well as those of the nucleobases adenine, guanine, cytosine, uracil, and thymine. Based on the oxygen dependence of the enzymes, their conservation, and evolution, we speculate on the relative antiquity of the pathways. Our results allow us to suggest which catabolic pathways and enzymes may have already been present in the last common ancestor. We conclude that the enzymatic degradations of ribose, as well as those of purines adenine and guanine, are among the most ancient catabolic pathways which can be traced by protein-based methodologies.}, } @article {pmid29188321, year = {2018}, author = {Cui, H and Su, X and Wei, S and Zhu, Y and Lu, Z and Wang, Y and Li, Y and Liu, H and Zhang, S and Pang, S}, title = {Comparative Analyses of Methanogenic and Methanotrophic Communities Between Two Different Water Regimes in Controlled Wetlands on the Qinghai-Tibetan Plateau, China.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {484-491}, pmid = {29188321}, issn = {1432-0991}, support = {GZH201400308//The Funds of Oil and Gas Survey, China Geological Survey/ ; }, mesh = {Autotrophic Processes ; Bacteria/classification/genetics/isolation & purification/*metabolism ; Methane/*metabolism ; Phylogeny ; Tibet ; Water/chemistry ; *Water Microbiology ; Wetlands ; }, abstract = {Wetlands are an important methane (CH4) emission source. CH4 is mainly produced during the biogeochemical process, in which methanogens and methanotrophs both play important roles. However, little is known how these two microbial communities change under different water regimes. In this study, the diversity and abundance of methanogens and methanotrophs in wetlands on Qinghai-Tibetan Plateau with different water contents (a high water content site DZ2-14-3 and a low water content site DZ2-14-4) were studied by using phylogenetic analysis and quantitative PCR based on mcrA gene and pmoA gene. A total of 16 methanogenic operational taxonomic units (OTUs) and 9 methanotrophic OTUs are obtained. For methanogens, Fen cluster (58.0%) and Methanosaetaceae (20.3%) are the dominant groups in high moisture samples, whereas Methanosaetaceae (32.4%), Methanosarcinaceae (29.4%), and Methanobacteriaceae (22.1%) are prevalent in low moisture samples. Methylobacter (90.0%) of type I methanotrophs are overwhelmingly dominant in high moisture samples, while Methylocystis (53.3%) and Methylomonas (42.2%) belonging to types II and I methanotrophs are the predominant groups in low moisture samples. Furthermore, qPCR analysis revealed that the abundance of methanogens and methanotrophs were higher in high moisture samples than that in low moisture samples. Overall, this comparative study between wetlands controlled by two different water regimes on the Qinghai-Tibetan Plateau provides fundamental data for further research on microbial functions within extreme ecosystems.}, } @article {pmid29188320, year = {2018}, author = {Diop, K and Andrieu, C and Michelle, C and Armstrong, N and Bittar, F and Bretelle, F and Fournier, PE and Raoult, D and Fenollar, F}, title = {Characterization of a New Ezakiella Isolated from the Human Vagina: Genome Sequence and Description of Ezakiella massiliensis sp. nov.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {456-463}, doi = {10.1007/s00284-017-1402-z}, pmid = {29188320}, issn = {1432-0991}, mesh = {Adult ; Bacterial Typing Techniques ; Fatty Acids/chemistry/metabolism ; Female ; Firmicutes/classification/genetics/*isolation & purification/metabolism ; *Genome, Bacterial ; Humans ; Phylogeny ; Vagina/*microbiology ; Vaginosis, Bacterial/*microbiology ; Young Adult ; }, abstract = {The study of the vaginal microbiota using the "culturomics concept" allowed us to isolate, from the vaginal swab of an asymptomatic 20-year-old woman who had sexual relations with another woman with bacterial vaginosis, an unknown Gram-positive anaerobic coccus-shaped bacterium that was designated strain Marseille-P2951T and characterized using taxono-genomics. Strain Marseille-P2951T is non-motile and non-spore forming and exhibits catalase and oxidase activities. Its 16S rRNA gene-based identification showed 98.5% identity with Ezakiella peruensis, the phylogenetically closest species. The major fatty acids are C18:1n9 (58%) and C16:0 (22%). With a 1,741,785 bp length, the G+C content of the genome is 36.69%. Of a total of 1657 genes, 1606 are protein-coding genes and 51 RNAs. Also, 1123 genes are assigned a putative function and 127 are ORFans. Phenotypic, phylogenetic, and genomics analyses revealed that strain Marseille-P2951T (=CSUR P2951 =DSM 103122) is distinct and represents a new species of the genus Ezakiella, for which the name Ezakiella massiliensis sp. nov. is proposed.}, } @article {pmid29186430, year = {2018}, author = {Kia, SH and Jurkechova, M and Glynou, K and Piepenbring, M and Maciá-Vicente, JG}, title = {The effects of fungal root endophytes on plant growth are stable along gradients of abiotic habitat conditions.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix162}, pmid = {29186430}, issn = {1574-6941}, abstract = {Plant symbioses with fungal root endophytes span a continuum from mutualistic to parasitic outcomes, and are highly variable depending on the genotype of each symbiont. The abiotic context in which interactions occur also seems to influence the outcome of plant-endophyte symbioses, but we lack understanding of its relative importance. We aimed to assess if changes in abiotic variables determine the effects of fungal root endophytes on plant growth. We used in vitro co-cultivation assays to test the impact of a selection of endophytic strains from diverse lineages on the growth of Arabidopsis thaliana, Microthlaspi erraticum and Hordeum vulgare along gradients of nutrient availability, light intensity or substrate pH. Most fungi showed a negative but weak effect on plant growth, whereas only a few had persistent detrimental effects across plants and conditions. Changes in abiotic factors affected plant growth but had little influence on their response to fungal inoculation. Of the factors tested, variation in nutrient availability resulted in the most variable plant-endophyte interactions, although changes were feeble and strain-specific. Our findings suggest that the effects of root endophytes on plant growth are robust to changes in the abiotic environment when these encompass the tolerance range of either symbiont.}, } @article {pmid29186405, year = {2018}, author = {Bleidorn, C and Gerth, M}, title = {A critical re-evaluation of multilocus sequence typing (MLST) efforts in Wolbachia.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix163}, pmid = {29186405}, issn = {1574-6941}, abstract = {Wolbachia (Alphaproteobacteria, Rickettsiales) is the most common, and arguably one of the most important inherited symbionts. Molecular differentiation of Wolbachia strains is routinely performed with a set of five multilocus sequence typing (MLST) markers. However, since its inception in 2006, the performance of MLST in Wolbachia strain typing has not been assessed objectively. Here, we evaluate the properties of Wolbachia MLST markers and compare it to 252 other single copy loci present in the genome of most Wolbachia strains. Specifically, we investigated how well MLST performs at strain differentiation, at reflecting genetic diversity of strains, and as phylogenetic marker. We find that MLST loci are outperformed by other loci at all tasks they are currently employed for, and thus that they do not reflect the properties of a Wolbachia strain very well. We argue that whole genome typing approaches should be used for Wolbachia typing in the future. Alternatively, if few loci approaches are necessary, we provide a characterisation of 252 single copy loci for a number a criteria, which may assist in designing specific typing systems or phylogenetic studies.}, } @article {pmid29186126, year = {2018}, author = {Wartewig, T and Kurgyis, Z and Keppler, S and Pechloff, K and Hameister, E and Öllinger, R and Maresch, R and Buch, T and Steiger, K and Winter, C and Rad, R and Ruland, J}, title = {Erratum: PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {238}, doi = {10.1038/nature25142}, pmid = {29186126}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature24649.}, } @article {pmid29186121, year = {2018}, author = {Karliner, M and Rosner, JL}, title = {Erratum: Quark-level analogue of nuclear fusion with doubly heavy baryons.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {238}, pmid = {29186121}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature21697.}, } @article {pmid29186118, year = {2018}, author = {Panigrahi, P and Parida, S and Nanda, NC and Satpathy, R and Pradhan, L and Chandel, DS and Baccaglini, L and Mohapatra, A and Mohapatra, SS and Misra, PR and Chaudhry, R and Chen, HH and Johnson, JA and Morris, JG and Paneth, N and Gewolb, IH}, title = {Corrigendum: A randomized synbiotic trial to prevent sepsis among infants in rural India.}, journal = {Nature}, volume = {553}, number = {7687}, pages = {238}, pmid = {29186118}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature23480.}, } @article {pmid29186114, year = {2018}, author = {Dalin, C and Wada, Y and Kastner, T and Puma, MJ}, title = {Corrigendum: Groundwater depletion embedded in international food trade.}, journal = {Nature}, volume = {553}, number = {7688}, pages = {366}, doi = {10.1038/nature24664}, pmid = {29186114}, issn = {1476-4687}, abstract = {This corrects the article DOI: 10.1038/nature21403.}, } @article {pmid29185955, year = {2018}, author = {Choi, GM and Im, WT}, title = {Paraburkholderia azotifigens sp. nov., a nitrogen-fixing bacterium isolated from paddy soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {310-316}, doi = {10.1099/ijsem.0.002505}, pmid = {29185955}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Burkholderiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nitrogen Fixation ; Nucleic Acid Hybridization ; Oryza ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile and rod-shaped bacterial strain, designated NF2-5-3T, was isolated from a paddy soil in Anseong city, Republic of Korea. This bacterium was characterized to determine its taxonomic position using a polyphasic approach. On the basis of 16S rRNA gene sequence analysis, strain NF2-5-3T had a close relationship with, and was related most closely to, members of the genus Paraburkholderia, namely Paraburkholderia caribensis MWAP64T (98.8 % similarity), P. sabiae Br3407T (98.8 %), P. hospita LMG 20598T (98.5 %), P. terrae NBRC 100964T (98.3 %) and P. phymatum STM815T (98.1 %). Growth of strain NF2-5-3T occurred at 15-37 °C, at pH 6.0-8.0 and at NaCl concentrations of 0-2 % (w/v). The major respiratory quinone was ubiquinone 8 (Q-8) and the major fatty acids were C16 : 0, summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c), C17 : 0 cyclo and C16 : 0 3-OH. The polar lipid profile consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, an unidentified phospholipid, unidentified aminophospholipids, unidentified aminolipids and unidentified polar lipids. The G+C content of the genomic DNA was 64.2 mol%. DNA-DNA relatedness values between strain NF2-5-3T and its closest phylogenetic neighbours were much lower than 70 %. Strain NF2-5-3T could be differentiated phylogenetically and phenotypically from recognized species of the genus Paraburkholderia. The isolate therefore represents a novel species, for which the name Paraburkholderia azotifigens sp. nov. is proposed, with NF2-5-3T (=KACC 18968T=LMG 29961T) as the type strain.}, } @article {pmid29185939, year = {2018}, author = {Chaudhary, DK and Kim, J}, title = {Flavobacterium naphthae sp. nov., isolated from oil-contaminated soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {305-309}, doi = {10.1099/ijsem.0.002504}, pmid = {29185939}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Nepal ; Nucleic Acid Hybridization ; *Petroleum Pollution ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {During a study of petroleum hydrocarbon-degrading bacteria, a yellow-coloured, Gram-stain-negative, non-motile and rod-shaped bacterium, designated strain Brt-MT, was isolated from oil-contaminated soil of Biratnagar, Morang, Nepal. Strain Brt-MT was able to grow at 15-45 °C, pH 5.0-9.0 and 0-1 % (w/v) NaCl concentration. The strain was characterized by multiple taxonomic approaches. Based on 16S rRNA gene sequence analysis, strain Brt-MT belonged to the genus Flavobacterium and shared highest sequence similarity with Flavobacterium cloacae wh15T (95.69 %) and Flavobacterium anatoliense MK3T (94.91 %). The only respiratory quinone was MK-6; the major polar lipid was phosphatidylethanolamine; and the predominant fatty acids were iso-C15 : 0, summed feature 9 (iso-C17 : 1ω9c and/or C16 : 010-methyl), iso-C17 : 0 3-OH and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The DNA G+C content was 37.2 mol%. The morphological, physiological, chemotaxonomic and phylogenetic analyses clearly distinguished this strain from its closest phylogenetic neighbours. Thus, strain Brt-MT represents a novel species of the genus Flavobacterium, for which the name Flavobacteriumnaphthae sp. nov. is proposed. The type strain is Brt-MT (=KEMB 9005-692T=KACC 19393T=JCM 32171T).}, } @article {pmid29185938, year = {2018}, author = {Pal, D and Bhardwaj, A and Sudan, SK and Kaur, N and Kumari, M and Bisht, B and Vyas, B and Krishnamurthi, S and Mayilraj, S}, title = {Thauera propionica sp. nov., isolated from downstream sediment sample of the river Ganges, Kanpur, India.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {341-346}, doi = {10.1099/ijsem.0.002508}, pmid = {29185938}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; India ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; Thauera/*classification/genetics/isolation & purification ; Ubiquinone/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, non-endospore-producing, short-rod strain, KNDSS-Mac4T, was isolated from a downstream sediment sample of the river Ganges, Kanpur, India and studied by using the polyphasic taxonomic approach. 16S rRNA gene sequence analysis uncovered that the strain had similarity to species of the genus Thauera and formed a distinct phylogenetic cluster with Thauera humireducens KACC16524T. However, KNDSS-Mac4T showed closest phylogenetic affiliation to Thauera aminoaromatica DSM 14742T with 16S rRNA gene sequence similarity of 98.7 % followed by Thauera phenylacetica DSM 14743T (98.6 %), Thauera chlorobenzoica (98.2 %), T. humireducens KACC16524T (98.2 %), Thauera selenatis ATCC 55363T (98.2 %) and Thauera mechernichensis DSM 12266T (98.0 %). The digital DNA-DNA hybridization and average nucleotide identity values between strain KNDSS-Mac4T and the two most closely related taxa, T. aminoaromatica DSM 14742T and T. phenylacetica DSM 14743T, were 26.0, 26.7 and 84.0, 84.3 % respectively. Major lipids present were phosphatidylglycerol, three unknown aminophospholipids, phosphatidylmethylethanolamine, two unidentified lipids and Q-8 as the only ubiquonone. The major cellular fatty acids present were C16 : 1 ω6c/C16 : 1ω7c and C16 : 0. The DNA G+C content of strain KNDSS-Mac4T was 65.9 %. Based on data from phenotypic tests and the genotypic differences of strain KNDSS-Mac4T from its closest phylogenetic relatives, it is evident that this isolate should be regarded as a new species. It is proposed that strain KNDSS-Mac4T should be classified in the genus Thauera as a novel species, Thauerapropionica sp. nov. The type strain is KNDSS-Mac4T (=KCTC 52820T=VTCC-B-910017T).}, } @article {pmid29185937, year = {2018}, author = {Xiao, M and Salam, N and Liu, L and Jiao, JY and Zheng, ML and Wang, J and Li, S and Chen, C and Li, WJ and Qu, PH}, title = {Fastidiosibacter lacustris gen. nov., sp. nov., isolated from a lake water sample, and proposal of Fastidiosibacteraceae fam. nov. within the order Thiotrichales.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {347-352}, doi = {10.1099/ijsem.0.002510}, pmid = {29185937}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Lakes/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {AFrancisella-like bacterium, designated strain SYSU HZH-2T, was isolated from a water sample collected from Haizhu Lake, Guangzhou, China. The bacterium was fastidious, and required an exogenous source of l-cysteine for its growth on artificial media. Cells were Gram-stain-negative, coccobacilli, non-motile and non-spore-forming. The strain shared highest 16S rRNA gene sequence similarities with Cysteiniphilum litorale SYSU D3-2T (94.6 % identity), Fangia hongkongensis UST040201-002T (93.2 %) and Caedibacter taeniospiralis 51T (91.6 %). This strain possessed ubiquinone-8 as the respiratory quinone; diphosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine and phosphatidylglycerol as the known polar lipids, and anteiso-C15 : 0 and C18 : 0 as the major fatty acids (>10 % of total fatty acids). The dendrograms based on 16S rRNA gene sequence analysis showed that it formed a separate cluster along with Cysteiniphilum litorale SYSU D3-2T, Caedibactertaeiniospiralis 51T and Fangia hongkongensis UST040201-002T. Based on the 16S rRNA gene sequence identity and differences in other phenotypic characteristics, the strain is considered to represent a novel species of a novel genus, for which the name Fastidiosibacter lacustris gen. nov., sp. nov. is proposed. The type strain of the type species Fastidiosibacter lacustris is SYSU HZH-2T (=NBRC 112274T = CGMCC 1.15950T). Additionally, the new taxon along with the genera Caedibacter, Cysteiniphilum and Fangia (family unassigned) were distinctly separated from the related families Francisellaceae, Piscirickettsiaceae and Thiotrichaeae in the phylogenetic trees. Therefore, we proposed a new family Fastidiosibacteraceae fam. nov. within the order Thiotrichales to accommodate these four genera.}, } @article {pmid29183985, year = {2018}, author = {Figueroa, IA and Barnum, TP and Somasekhar, PY and Carlström, CI and Engelbrektson, AL and Coates, JD}, title = {Metagenomics-guided analysis of microbial chemolithoautotrophic phosphite oxidation yields evidence of a seventh natural CO2 fixation pathway.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {1}, pages = {E92-E101}, pmid = {29183985}, issn = {1091-6490}, mesh = {Carbon Dioxide/*metabolism ; Chemoautotrophic Growth/*physiology ; *Deltaproteobacteria/genetics/metabolism ; *Metagenomics ; Oxidation-Reduction ; Phosphites/*metabolism ; Sewage/*microbiology ; Waste Water/*microbiology ; *Water Microbiology ; Water Purification ; }, abstract = {Dissimilatory phosphite oxidation (DPO), a microbial metabolism by which phosphite (HPO32-) is oxidized to phosphate (PO43-), is the most energetically favorable chemotrophic electron-donating process known. Only one DPO organism has been described to date, and little is known about the environmental relevance of this metabolism. In this study, we used 16S rRNA gene community analysis and genome-resolved metagenomics to characterize anaerobic wastewater treatment sludge enrichments performing DPO coupled to CO2 reduction. We identified an uncultivated DPO bacterium, Candidatus Phosphitivorax (Ca. P.) anaerolimi strain Phox-21, that belongs to candidate order GW-28 within the Deltaproteobacteria, which has no known cultured isolates. Genes for phosphite oxidation and for CO2 reduction to formate were found in the genome of Ca. P. anaerolimi, but it appears to lack any of the known natural carbon fixation pathways. These observations led us to propose a metabolic model for autotrophic growth by Ca. P. anaerolimi whereby DPO drives CO2 reduction to formate, which is then assimilated into biomass via the reductive glycine pathway.}, } @article {pmid29183972, year = {2018}, author = {Fernandes, JB and Séguéla-Arnaud, M and Larchevêque, C and Lloyd, AH and Mercier, R}, title = {Unleashing meiotic crossovers in hybrid plants.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {10}, pages = {2431-2436}, pmid = {29183972}, issn = {1091-6490}, support = {281659//European Research Council/International ; }, mesh = {Arabidopsis/*genetics/*physiology ; *Breeding ; Crossing Over, Genetic/*genetics ; Genes, Plant/genetics ; Homologous Recombination/*genetics ; Mutation/genetics ; }, abstract = {Meiotic crossovers shuffle parental genetic information, providing novel combinations of alleles on which natural or artificial selection can act. However, crossover events are relatively rare, typically one to three exchange points per chromosome pair. Recent work has identified three pathways limiting meiotic crossovers in Arabidopsis thaliana that rely on the activity of FANCM [Crismani W, et al. (2012) Science 336:1588-1590], RECQ4 [Séguéla-Arnaud M, et al. (2015) Proc Natl Acad Sci USA 112:4713-4718], and FIGL1 [Girard C, et al. (2015) PLoS Genet 11:e1005369]. Here we analyzed recombination in plants in which one, two, or all three of these pathways were disrupted in both pure line and hybrid contexts. The greatest effect was observed when combining recq4 and figl1 mutations, which increased the hybrid genetic map length from 389 to 3,037 cM. This corresponds to an unprecedented 7.8-fold increase in crossover frequency. Disrupting the three pathways did not further increase recombination, suggesting that some upper limit had been reached. The increase in crossovers is not uniform along chromosomes and rises from centromere to telomere. Finally, although in wild type recombination is much higher in male meiosis than in female meiosis (490 cM vs. 290 cM), female recombination is higher than male recombination in recq4 figl1 (3,200 cM vs. 2,720 cM), suggesting that the factors that make wild-type female meiosis less recombinogenic than male wild-type meiosis do not apply in the mutant context. The massive increase in recombination observed in recq4 figl1 hybrids opens the possibility of manipulating recombination to enhance plant breeding efficiency.}, } @article {pmid29183737, year = {2018}, author = {Magella, B and Adam, M and Potter, AS and Venkatasubramanian, M and Chetal, K and Hay, SB and Salomonis, N and Potter, SS}, title = {Cross-platform single cell analysis of kidney development shows stromal cells express Gdnf.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {36-47}, pmid = {29183737}, issn = {1095-564X}, support = {P50 DK096418/DK/NIDDK NIH HHS/United States ; R01 DK099995/DK/NIDDK NIH HHS/United States ; U01 DK070251/DK/NIDDK NIH HHS/United States ; U01 HL099997/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Gene Expression Profiling/*methods ; Gene Expression Regulation, Developmental/*physiology ; Glial Cell Line-Derived Neurotrophic Factor/*biosynthesis ; Homeodomain Proteins/biosynthesis ; In Situ Hybridization/*methods ; Mesenchymal Stem Cells/cytology/*metabolism ; Mice ; Myeloid Ecotropic Viral Integration Site 1 Protein/biosynthesis ; Nephrons/cytology/*embryology ; Transcription Factors/biosynthesis ; }, abstract = {The developing kidney provides a useful model for study of the principles of organogenesis. In this report we use three independent platforms, Drop-Seq, Chromium 10x Genomics and Fluidigm C1, to carry out single cell RNA-Seq (scRNA-Seq) analysis of the E14.5 mouse kidney. Using the software AltAnalyze, in conjunction with the unsupervised approach ICGS, we were unable to identify and confirm the presence of 16 distinct cell populations during this stage of active nephrogenesis. Using a novel integrative supervised computational strategy, we were able to successfully harmonize and compare the cell profiles across all three technological platforms. Analysis of possible cross compartment receptor/ligand interactions identified the nephrogenic zone stroma as a source of GDNF. This was unexpected because the cap mesenchyme nephron progenitors had been thought to be the sole source of GDNF, which is a key driver of branching morphogenesis of the collecting duct system. The expression of Gdnf by stromal cells was validated in several ways, including Gdnf in situ hybridization combined with immunohistochemistry for SIX2, and marker of nephron progenitors, and MEIS1, a marker of stromal cells. Finally, the single cell gene expression profiles generated in this study confirmed and extended previous work showing the presence of multilineage priming during kidney development. Nephron progenitors showed stochastic expression of genes associated with multiple potential differentiation lineages.}, } @article {pmid29183717, year = {2018}, author = {Dorigatti, I and McCormack, C and Nedjati-Gilani, G and Ferguson, NM}, title = {Using Wolbachia for Dengue Control: Insights from Modelling.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {102-113}, pmid = {29183717}, issn = {1471-5007}, support = {U01 GM110721/GM/NIGMS NIH HHS/United States ; //Medical Research Council/United Kingdom ; }, mesh = {Aedes/*microbiology ; Animals ; *Biological Control Agents ; Dengue/*prevention & control/transmission ; Dengue Virus/*physiology ; Insect Vectors/microbiology ; *Models, Theoretical ; Wolbachia/*physiology ; }, abstract = {Dengue is the most common arboviral infection of humans, responsible for a substantial disease burden across the tropics. Traditional insecticide-based vector-control programmes have limited effectiveness, and the one licensed vaccine has a complex and imperfect efficacy profile. Strains of the bacterium Wolbachia, deliberately introduced into Aedes aegyptimosquitoes, have been shown to be able to spread to high frequencies in mosquito populations in release trials, and mosquitoes infected with these strains show markedly reduced vector competence. Thus, Wolbachia represents an exciting potential new form of biocontrol for arboviral diseases, including dengue. Here, we review how mathematical models give insight into the dynamics of the spread of Wolbachia, the potential impact of Wolbachia on dengue transmission, and we discuss the remaining challenges in evaluation and development.}, } @article {pmid29182912, year = {2018}, author = {Gruber, S}, title = {SMC complexes sweeping through the chromosome: going with the flow and against the tide.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {96-103}, doi = {10.1016/j.mib.2017.10.004}, pmid = {29182912}, issn = {1879-0364}, mesh = {Bacterial Proteins/*genetics/metabolism ; Cell Cycle Proteins/*genetics/metabolism ; Chromosome Segregation ; Chromosomes, Bacterial/*genetics/metabolism ; DNA Replication/genetics ; DNA, Bacterial/*genetics ; Multiprotein Complexes/genetics/metabolism ; }, abstract = {Bacteria transcribe, duplicate and segregate their genomes all at once. Conflicts between DNA replication and active transcription are a major source of DNA damage and jeopardize genome integrity and cell survival. Co-orientation of replication forks and transcription units is thought to reduce the impact of such conflicts. Like transcription and replication, chromosome segregation relies on the translocation of multi-subunit protein complexes along DNA. Here, I highlight recent advances in our understanding of two major classes of structural maintenance of chromosomes (SMC) complexes in bacteria: Smc-ScpAB, whose DNA translocation is co-oriented with DNA replication by specific start sites, and MukBEF, which apparently lacks such co-ordination. Potential advantages of centralized and decentralized approaches to chromosome organization are discussed.}, } @article {pmid29182740, year = {2018}, author = {Nilsson, MA and Zheng, Y and Kumar, V and Phillips, MJ and Janke, A}, title = {Speciation Generates Mosaic Genomes in Kangaroos.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {33-44}, pmid = {29182740}, issn = {1759-6653}, mesh = {Animals ; Australia ; *Genetic Speciation ; Genome ; Genome, Mitochondrial ; Macropodidae/classification/*genetics ; Mosaicism ; *Phylogeny ; }, abstract = {The iconic Australasian kangaroos and wallabies represent a successful marsupial radiation. However, the evolutionary relationship within the two genera, Macropus and Wallabia, is controversial: mitochondrial and nuclear genes, and morphological data have produced conflicting scenarios regarding the phylogenetic relationships, which in turn impact the classification and taxonomy. We sequenced and analyzed the genomes of 11 kangaroos to investigate the evolutionary cause of the observed phylogenetic conflict. A multilocus coalescent analysis using ∼14,900 genome fragments, each 10 kb long, significantly resolved the species relationships between and among the sister-genera Macropus and Wallabia. The phylogenomic approach reconstructed the swamp wallaby (Wallabia) as nested inside Macropus, making this genus paraphyletic. However, the phylogenomic analyses indicate multiple conflicting phylogenetic signals in the swamp wallaby genome. This is interpreted as at least one introgression event between the ancestor of the genus Wallabia and a now extinct ghost lineage outside the genus Macropus. Additional phylogenetic signals must therefore be caused by incomplete lineage sorting and/or introgression, but available statistical methods cannot convincingly disentangle the two processes. In addition, the relationships inside the Macropus subgenus M. (Notamacropus) represent a hard polytomy. Thus, the relationships between tammar, red-necked, agile, and parma wallabies remain unresolvable even with whole-genome data. Even if most methods resolve bifurcating trees from genomic data, hard polytomies, incomplete lineage sorting, and introgression complicate the interpretation of the phylogeny and thus taxonomy.}, } @article {pmid29181783, year = {2018}, author = {Jo, E and Park, SN and Lim, YK and Paek, J and Shin, Y and Kim, H and Kim, SH and Shin, JH and Chang, YH and Kook, JK}, title = {Capnocytophaga endodontalis sp. nov., Isolated from a Human Refractory Periapical Abscess.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {420-425}, pmid = {29181783}, issn = {1432-0991}, support = {2017M3A9B8065844//the Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science and ICT/ ; 2013M3A9A5076603//the KRIBB Research Initiative Program funded by the Ministry of Science, ICT, and Future Planning/ ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; Capnocytophaga/classification/genetics/*isolation & purification/metabolism ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry/metabolism ; Gram-Negative Bacterial Infections/*microbiology ; Humans ; Periapical Abscess/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {A novel Gram-negative, capnophilic, fusiform bacterium, designated strain ChDC OS43T, was isolated from a human refractory periapical abscess in the left mandibular second molar and was characterized by polyphasic taxonomic analysis. The 16S rRNA gene sequence revealed that the strain belongs to the genus Capnocytophaga, as it showed sequence similarities to Capnocytophaga ochracea ATCC 27872T (96.30%) and C. sputigena ATCC 33612T (96.16%). The prevalent fatty acids of strain ChDC OS43T were isoC15:0 (57.54%), C16:0 (5.93%), C16:0 3OH (5.72%), and C18:1 cis 9 (4.41%). The complete genome of strain ChDC OS43T was 3,412,686 bp, and the G+C content was 38.2 mol%. The average nucleotide identity (ANI) value between strain ChDC OS43T and C. ochracea ATCC 27872T or C. sputigena ATCC 33612T was >92.01%. The genome-to-genome distance (GGD) value between strain ChDC OS43T and C. ochracea ATCC 27872T or C. sputigena ATCC 33612T was 32.0 and 45.7%, respectively. Based on the results of phenotypic, chemotaxonomic, and phylogenetic analysis, strain ChDC OS43T (= KCOM 1579T = KCTC 5562T = KCCM 42841T = JCM 32133T) should be classified as the type strain of a novel species of genus Capnocytophaga, for which the name Capnocytophaga endodontalis sp. nov. is proposed.}, } @article {pmid29180726, year = {2018}, author = {Schulfer, AF and Battaglia, T and Alvarez, Y and Bijnens, L and Ruiz, VE and Ho, M and Robinson, S and Ward, T and Cox, LM and Rogers, AB and Knights, D and Sartor, RB and Blaser, MJ}, title = {Intergenerational transfer of antibiotic-perturbed microbiota enhances colitis in susceptible mice.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {234-242}, pmid = {29180726}, issn = {2058-5276}, support = {P30 CA016087/CA/NCI NIH HHS/United States ; P40 OD010995/OD/NIH HHS/United States ; P30 DK034987/DK/NIDDK NIH HHS/United States ; P30 CA016086/CA/NCI NIH HHS/United States ; R01 DK090989/DK/NIDDK NIH HHS/United States ; }, abstract = {Antibiotic exposure in children has been associated with the risk of inflammatory bowel disease (IBD). Antibiotic use in children or in their pregnant mother can affect how the intestinal microbiome develops, so we asked whether the transfer of an antibiotic-perturbed microbiota from mothers to their children could affect their risk of developing IBD. Here we demonstrate that germ-free adult pregnant mice inoculated with a gut microbial community shaped by antibiotic exposure transmitted their perturbed microbiota to their offspring with high fidelity. Without any direct or continued exposure to antibiotics, this dysbiotic microbiota in the offspring remained distinct from controls for at least 21 weeks. By using both IL-10-deficient and wild-type mothers, we showed that both inoculum and genotype shape microbiota populations in the offspring. Because IL10-/- mice are genetically susceptible to colitis, we could assess the risk due to maternal transmission of an antibiotic-perturbed microbiota. We found that the IL10-/- offspring that had received the perturbed gut microbiota developed markedly increased colitis. Taken together, our findings indicate that antibiotic exposure shaping the maternal gut microbiota has effects that extend to the offspring, with both ecological and long-term disease consequences.}, } @article {pmid29180725, year = {2018}, author = {Kamareddine, L and Wong, ACN and Vanhove, AS and Hang, S and Purdy, AE and Kierek-Pearson, K and Asara, JM and Ali, A and Morris, JG and Watnick, PI}, title = {Activation of Vibrio cholerae quorum sensing promotes survival of an arthropod host.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {243-252}, pmid = {29180725}, issn = {2058-5276}, support = {R01 AI097405/AI/NIAID NIH HHS/United States ; P01 CA120964/CA/NCI NIH HHS/United States ; P40 OD018537/OD/NIH HHS/United States ; R21 AI109436/AI/NIAID NIH HHS/United States ; R01 AI112652/AI/NIAID NIH HHS/United States ; P30 CA006516/CA/NCI NIH HHS/United States ; R01 AI071147/AI/NIAID NIH HHS/United States ; }, abstract = {Vibrio cholerae colonizes the human terminal ileum to cause cholera, and the arthropod intestine and exoskeleton to persist in the aquatic environment. Attachment to these surfaces is regulated by the bacterial quorum-sensing signal transduction cascade, which allows bacteria to assess the density of microbial neighbours. Intestinal colonization with V. cholerae results in expenditure of host lipid stores in the model arthropod Drosophila melanogaster. Here we report that activation of quorum sensing in the Drosophila intestine retards this process by repressing V. cholerae succinate uptake. Increased host access to intestinal succinate mitigates infection-induced lipid wasting to extend survival of V. cholerae-infected flies. Therefore, quorum sensing promotes a more favourable interaction between V. cholerae and an arthropod host by reducing the nutritional burden of intestinal colonization.}, } @article {pmid29180711, year = {2018}, author = {van Denderen, PD and Lindegren, M and MacKenzie, BR and Watson, RA and Andersen, KH}, title = {Global patterns in marine predatory fish.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {65-70}, doi = {10.1038/s41559-017-0388-z}, pmid = {29180711}, issn = {2397-334X}, mesh = {*Animal Distribution ; Animals ; Fishes/*physiology ; *Food Chain ; Models, Biological ; Oceans and Seas ; *Predatory Behavior ; }, abstract = {Large teleost (bony) fish are a dominant group of predators in the oceans and constitute a major source of food and livelihood for humans. These species differ markedly in morphology and feeding habits across oceanic regions; large pelagic species such as tunas and billfish typically occur in the tropics, whereas demersal species of gadoids and flatfish dominate boreal and temperate regions. Despite their importance for fisheries and the structuring of marine ecosystems, the underlying factors determining the global distribution and productivity of these two groups of teleost predators are poorly known. Here, we show how latitudinal differences in predatory fish can essentially be explained by the inflow of energy at the base of the pelagic and benthic food chain. A low productive benthic energy pathway favours large pelagic species, whereas equal productivities support large demersal generalists that outcompete the pelagic specialists. Our findings demonstrate the vulnerability of large teleost predators to ecosystem-wide changes in energy flows and hence provide key insight to predict the responses of these important marine resources under global change.}, } @article {pmid29180710, year = {2018}, author = {Meyer, ST and Ptacnik, R and Hillebrand, H and Bessler, H and Buchmann, N and Ebeling, A and Eisenhauer, N and Engels, C and Fischer, M and Halle, S and Klein, AM and Oelmann, Y and Roscher, C and Rottstock, T and Scherber, C and Scheu, S and Schmid, B and Schulze, ED and Temperton, VM and Tscharntke, T and Voigt, W and Weigelt, A and Wilcke, W and Weisser, WW}, title = {Biodiversity-multifunctionality relationships depend on identity and number of measured functions.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {44-49}, doi = {10.1038/s41559-017-0391-4}, pmid = {29180710}, issn = {2397-334X}, mesh = {*Biodiversity ; Conservation of Natural Resources ; Germany ; *Grassland ; Models, Biological ; Plants ; }, abstract = {Biodiversity ensures ecosystem functioning and provisioning of ecosystem services, but it remains unclear how biodiversity-ecosystem multifunctionality relationships depend on the identity and number of functions considered. Here, we demonstrate that ecosystem multifunctionality, based on 82 indicator variables of ecosystem functions in a grassland biodiversity experiment, increases strongly with increasing biodiversity. Analysing subsets of functions showed that the effects of biodiversity on multifunctionality were stronger when more functions were included and that the strength of the biodiversity effects depended on the identity of the functions included. Limits to multifunctionality arose from negative correlations among functions and functions that were not correlated with biodiversity. Our findings underline that the management of ecosystems for the protection of biodiversity cannot be replaced by managing for particular ecosystem functions or services and emphasize the need for specific management to protect biodiversity. More plant species from the experimental pool of 60 species contributed to functioning when more functions were considered. An individual contribution to multifunctionality could be demonstrated for only a fraction of the species.}, } @article {pmid29180709, year = {2018}, author = {Reger, J and Lind, MI and Robinson, MR and Beckerman, AP}, title = {Predation drives local adaptation of phenotypic plasticity.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {100-107}, doi = {10.1038/s41559-017-0373-6}, pmid = {29180709}, issn = {2397-334X}, mesh = {*Adaptation, Biological ; Animals ; Biological Evolution ; Daphnia/genetics/*physiology ; Food Chain ; *Genetic Variation ; *Phenotype ; Predatory Behavior ; }, abstract = {Phenotypic plasticity is the ability of an individual genotype to alter aspects of its phenotype depending on the current environment. It is central to the persistence, resistance and resilience of populations facing variation in physical or biological factors. Genetic variation in plasticity is pervasive, which suggests its local adaptation is plausible. Existing studies on the adaptation of plasticity typically focus on single traits and a few populations, while theory about interactions among genes (for example, pleiotropy) suggests that a multi-trait, landscape scale (for example, multiple populations) perspective is required. We present data from a landscape scale, replicated, multi-trait experiment using a classic predator-prey system centred on the water flea Daphnia pulex. We find predator regime-driven differences in genetic variation of multivariate plasticity. These differences are associated with strong divergent selection linked to a predation regime. Our findings are evidence for local adaptation of plasticity, suggesting that responses of populations to environmental variation depend on the conditions in which they evolved in the past.}, } @article {pmid29180708, year = {2018}, author = {Stearns, SC}, title = {Outstanding research opportunities at the interface of evolution and medicine.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {3-4}, doi = {10.1038/s41559-017-0409-y}, pmid = {29180708}, issn = {2397-334X}, } @article {pmid29180707, year = {2018}, author = {Tonkin, JD and Merritt, DM and Olden, JD and Reynolds, LV and Lytle, DA}, title = {Flow regime alteration degrades ecological networks in riparian ecosystems.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {86-93}, doi = {10.1038/s41559-017-0379-0}, pmid = {29180707}, issn = {2397-334X}, mesh = {Biodiversity ; *Climate Change ; *Droughts ; *Ecosystem ; *Floods ; Models, Biological ; Plants ; *Rivers ; *Water Movements ; }, abstract = {Riverine ecosystems are governed by patterns of temporal variation in river flows. This dynamism will change due to climate change and the near-ubiquitous human control of river flows globally, which may have severe effects on species distributions and interactions. We employed a combination of population modelling and network theory to explore the consequences of possible flow regime futures on riparian plant communities, including scenarios of increased drought, flooding and flow homogenization (removal of flow variability). We found that even slight modifications to the historic natural flow regime had significant consequences for the structure of riparian plant networks. Networks of emergent interactions between plant guilds were most connected at the natural flow regime and became simplified with increasing flow alteration. The most influential component of flow alteration was flood reduction, with drought and flow homogenization both having greater simplifying community-wide consequences than increased flooding. These findings suggest that maintaining floods under future climates will be needed to overcome the negative long-term consequences of flow modification on riverine ecosystems.}, } @article {pmid29180706, year = {2018}, author = {Berthelot, C and Villar, D and Horvath, JE and Odom, DT and Flicek, P}, title = {Complexity and conservation of regulatory landscapes underlie evolutionary resilience of mammalian gene expression.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {152-163}, pmid = {29180706}, issn = {2397-334X}, support = {108749//Wellcome Trust/United Kingdom ; 202878FLICEK//Wellcome Trust/United Kingdom ; 615584//European Research Council/International ; }, mesh = {Animals ; Enhancer Elements, Genetic ; *Evolution, Molecular ; *Gene Expression ; Liver/metabolism ; Mammals/*genetics ; Promoter Regions, Genetic ; }, abstract = {To gain insight into how mammalian gene expression is controlled by rapidly evolving regulatory elements, we jointly analysed promoter and enhancer activity with downstream transcription levels in liver samples from 15 species. Genes associated with complex regulatory landscapes generally exhibit high expression levels that remain evolutionarily stable. While the number of regulatory elements is the key driver of transcriptional output and resilience, regulatory conservation matters: elements active across mammals most effectively stabilize gene expression. In contrast, recently evolved enhancers typically contribute weakly, consistent with their high evolutionary plasticity. These effects are observed across the entire mammalian clade and are robust to potential confounders, such as the gene expression level. Using liver as a representative somatic tissue, our results illuminate how the evolutionary stability of gene expression is profoundly entwined with both the number and conservation of surrounding promoters and enhancers.}, } @article {pmid29180705, year = {2018}, author = {Cattau, CE and Fletcher, RJ and Kimball, RT and Miller, CW and Kitchens, WM}, title = {Rapid morphological change of a top predator with the invasion of a novel prey.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {108-115}, doi = {10.1038/s41559-017-0378-1}, pmid = {29180705}, issn = {2397-334X}, mesh = {*Animal Distribution ; Animals ; Biological Evolution ; Falconiformes/*anatomy & histology/genetics/*physiology ; Female ; Florida ; Food Chain ; *Introduced Species ; Male ; *Phenotype ; Predatory Behavior ; Snails/*physiology ; }, abstract = {Invasive exotic species are spreading rapidly throughout the planet. These species can have widespread impacts on biodiversity, yet the ability for native species, particularly long-lived vertebrates, to respond rapidly to invasions remains mostly unknown. Here we provide evidence of rapid morphological change in the endangered snail kite (Rostrhamus sociabilis) across its North American range with the invasion of a novel prey, the island apple snail (Pomacea maculata), a much larger congener of the kite's native prey. In less than one decade since invasion, snail kite bill size and body mass increased substantially. Larger bills should be better suited to extracting meat from the larger snail shells, and we detected strong selection on increased size through juvenile survival. Using pedigree data, we found evidence of both genetic and environmental influences on trait expression and discovered that additive genetic variation in bill size increased with invasion. However, trends in predicted breeding values emphasize that recent morphological changes have been driven primarily by phenotypic plasticity rather than micro-evolutionary change. Our findings suggest that evolutionary change may be imminent and underscore that even long-lived vertebrates can respond quickly to invasive species. Furthermore, these results highlight that phenotypic plasticity may provide a crucial role for predators experiencing rapid environmental change.}, } @article {pmid29180699, year = {2018}, author = {Turcan, S and Makarov, V and Taranda, J and Wang, Y and Fabius, AWM and Wu, W and Zheng, Y and El-Amine, N and Haddock, S and Nanjangud, G and LeKaye, HC and Brennan, C and Cross, J and Huse, JT and Kelleher, NL and Osten, P and Thompson, CB and Chan, TA}, title = {Mutant-IDH1-dependent chromatin state reprogramming, reversibility, and persistence.}, journal = {Nature genetics}, volume = {50}, number = {1}, pages = {62-72}, pmid = {29180699}, issn = {1546-1718}, support = {T32 CA160001/CA/NCI NIH HHS/United States ; R01 MH096946/MH/NIMH NIH HHS/United States ; R01 CA177828/CA/NCI NIH HHS/United States ; P41 GM108569/GM/NIGMS NIH HHS/United States ; P30 CA008748/CA/NCI NIH HHS/United States ; }, abstract = {Mutations in IDH1 and IDH2 (encoding isocitrate dehydrogenase 1 and 2) drive the development of gliomas and other human malignancies. Mutant IDH1 induces epigenetic changes that promote tumorigenesis, but the scale and reversibility of these changes are unknown. Here, using human astrocyte and glioma tumorsphere systems, we generate a large-scale atlas of mutant-IDH1-induced epigenomic reprogramming. We characterize the reversibility of the alterations in DNA methylation, the histone landscape, and transcriptional reprogramming that occur following IDH1 mutation. We discover genome-wide coordinate changes in the localization and intensity of multiple histone marks and chromatin states. Mutant IDH1 establishes a CD24+ population with a proliferative advantage and stem-like transcriptional features. Strikingly, prolonged exposure to mutant IDH1 results in irreversible genomic and epigenetic alterations. Together, these observations provide unprecedented high-resolution molecular portraits of mutant-IDH1-dependent epigenomic reprogramming. These findings have substantial implications for understanding of mutant IDH function and for optimizing therapeutic approaches to targeting IDH-mutant tumors.}, } @article {pmid29180104, year = {2018}, author = {Marsden, AN and Derry, SW and Schneider, I and Scott, CA and Westfall, TA and Brastrom, LK and Shea, MA and Dawson, DV and Slusarski, DC}, title = {The Nkd EF-hand domain modulates divergent wnt signaling outputs in zebrafish.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {63-73}, doi = {10.1016/j.ydbio.2017.11.012}, pmid = {29180104}, issn = {1095-564X}, support = {P30 CA086862/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Calcium/*metabolism ; Calcium Signaling/*physiology ; Carrier Proteins/genetics/*metabolism ; Wnt Signaling Pathway/*physiology ; Zebrafish/genetics/*metabolism ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Wnt proteins regulate diverse biological responses by initiating two general outcomes: β-catenin-dependent transcription and β-catenin-independent activation of signaling cascades, the latter including modulation of calcium and regulation of cytoskeletal dynamics (Planar Cell Polarity, PCP). It has been difficult to elucidate the mechanisms by which Wnt signals are directed to effect one or the other outcome due to shared signaling proteins between the β-catenin-dependent and -independent pathways, such as the Dishevelled binding protein Naked. While all Naked paralogs contain a putative calcium-binding domain, the EF-Hand, Drosophila Naked does not bind calcium. Here we find a lineage-specific evolutionary change within the Drosophila Naked EF-hand that is not shared with other insects or vertebrates. We demonstrate the necessary role of the EF-hand for Nkd localization changes in calcium fluxing cells and using in vivo assays, we identify a role for the zebrafish Naked EF-hand in PCP but not in β-catenin antagonism. In contrast, Drosophila-like Nkd does not function in PCP, but is a robust antagonist of Wnt/β-catenin signaling. This work reveals that the zebrafish Nkd1 EF-hand is essential to balance Wnt signaling inputs and modulate the appropriate outputs, while the Drosophila-like EF-Hand primarily functions in β-catenin signaling.}, } @article {pmid29180103, year = {2018}, author = {Yang, LE and Zhou, W and Hu, CM and Deng, YY and Xu, GP and Zhang, T and Russell, S and Zhu, JY and Lu, QQ and Brodie, J}, title = {A molecular phylogeny of the bladed Bangiales (Rhodophyta) in China provides insights into biodiversity and biogeography of the genus Pyropia.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {94-102}, doi = {10.1016/j.ympev.2017.11.009}, pmid = {29180103}, issn = {1095-9513}, mesh = {Base Sequence ; Bayes Theorem ; *Biodiversity ; China ; DNA Barcoding, Taxonomic ; *Phylogeny ; *Phylogeography ; Rhodophyta/*classification ; Species Specificity ; }, abstract = {A molecular taxonomic study was undertaken for the first time of the bladed Bangiales of the mainland coast of China (Northwest Pacific) based on sequence data of 201 plastid rbcL and 148 nuclear 18S sequences of historical and contemporary specimens. The results revealed that only one genus of bladed Bangiales, Pyropia, was present along Chinese coast. Species delimitation was determined using two empirical methods: the Automatic Barcode Gap Discovery (ABGD) and General Mixed Yule Coalescence (GMYC) coupled with detection of monophyly in tree reconstruction. At least fourteen species of Pyropia were recovered. Six species were confirmed that had been recorded previously based on morphology (Py. suborbiculata, Py. yezoensis, Py. haitanensis, Py. katadae, Py. tenera and Py. acanthophora), three species were recorded from China for the first time (Py. kinositae, Py. pseudolinearis and Py. tanegashimensis), and five cryptic species that did not match any molecular sequences were also discovered. The phylogeny of the concatenated rbcL and 18S dataset resolved three singletons and four clades. Each clades has a strong trend towards occupying a biogeographic region, but they are not confined to them. A transoceanic and antitropical pattern of distribution was found for Pyropia at both the subgeneric and species level. This together with high biodiversity (ca. 30% of all known Pyropia species) indicates that the Northwest Pacific might act as a centre of origin for modern distribution of Pyropia since the early Cenozoic.}, } @article {pmid29180041, year = {2018}, author = {Germain, RM and Williams, JL and Schluter, D and Angert, AL}, title = {Moving Character Displacement beyond Characters Using Contemporary Coexistence Theory.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {2}, pages = {74-84}, doi = {10.1016/j.tree.2017.11.002}, pmid = {29180041}, issn = {1872-8383}, mesh = {Animals ; *Biological Evolution ; Biota ; Ecology/*methods ; Invertebrates ; *Phenotype ; Plants ; *Sympatry ; Vertebrates ; }, abstract = {Character displacement is one of the most studied phenomena in evolutionary biology, yet research has narrowly focused on demonstrating whether or not displacement has occurred. We propose a new experimental approach, adopted from the coexistence literature, that directly measures interspecific competition among sympatric and allopatric populations of species. Doing so allows increased ability to (i) test predictions of character displacement without biases inherent to character-centric tests, (ii) quantify its effect on the stability of coexistence, (iii) resolve the phenotypic pathways through which competitive divergence is achieved, and (iv) perform comparative tests. Our approach extends research to forms of character displacement not readily identified by past methods and will lead to a broader understanding of its consequences for community structure.}, } @article {pmid29179947, year = {2018}, author = {Chiou, K and Collins, ES}, title = {Why we need mechanics to understand animal regeneration.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {155-165}, doi = {10.1016/j.ydbio.2017.09.021}, pmid = {29179947}, issn = {1095-564X}, mesh = {Amphibians/physiology ; Animals ; Animals, Genetically Modified ; Body Patterning/physiology ; Cell Adhesion ; Cell Division ; Cell Movement ; Contractile Proteins/physiology ; Diffusion ; Embryonic Development ; Hydra/physiology ; *Mechanical Phenomena ; *Models, Animal ; Models, Biological ; Regeneration/*physiology ; Species Specificity ; Surface Tension ; Viscoelastic Substances ; }, abstract = {Mechanical forces are an important contributor to cell fate specification and cell migration during embryonic development in animals. Similarities between embryogenesis and regeneration, particularly with regards to pattern formation and large-scale tissue movements, suggest similarly important roles for physical forces during regeneration. While the influence of the mechanical environment on stem cell differentiation in vitro is being actively exploited in the fields of tissue engineering and regenerative medicine, comparatively little is known about the role of stresses and strains acting during animal regeneration. In this review, we summarize published work on the role of physical principles and mechanical forces in animal regeneration. Novel experimental techniques aimed at addressing the role of mechanics in embryogenesis have greatly enhanced our understanding at scales from the subcellular to the macroscopic - we believe the time is ripe for the field of regeneration to similarly leverage the tools of the mechanobiological research community.}, } @article {pmid29179946, year = {2018}, author = {Erickson, JR and Echeverri, K}, title = {Learning from regeneration research organisms: The circuitous road to scar free wound healing.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {144-154}, pmid = {29179946}, issn = {1095-564X}, support = {R01 HD092451/HD/NICHD NIH HHS/United States ; }, mesh = {Amphibians/physiology ; Animals ; Cicatrix/physiopathology/*prevention & control ; Extracellular Matrix/metabolism ; Fibroblasts/physiology ; Gene Expression Regulation ; Humans ; Invertebrates/physiology ; Keratinocytes/physiology ; Mammals/physiology ; *Models, Animal ; Prenatal Injuries/physiopathology ; Regeneration/physiology ; Skin/cytology/embryology ; Species Specificity ; Wound Healing/immunology/*physiology ; Zebrafish/physiology ; }, abstract = {The skin is the largest organ in the body and plays multiple essential roles ranging from regulating temperature, preventing infection and ultimately defining who we are physically. It is a highly dynamic organ that constantly replaces the outermost cells throughout life. However, when faced with a major injury, human skin cannot restore a significant lesion to its original functionality, instead a reparative scar is formed. In contrast to this, many other species have the unique ability to regenerate full thickness skin without formation of scar tissue. Here we review recent advances in the field that shed light on how the skin cells in regenerative species react to injury to prevent scar formation versus scar forming humans.}, } @article {pmid29179945, year = {2018}, author = {Sánchez Alvarado, A}, title = {To solve old problems, study new research organisms.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {111-114}, doi = {10.1016/j.ydbio.2017.09.018}, pmid = {29179945}, issn = {1095-564X}, support = {R37 GM057260/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Animals, Laboratory/physiology ; Biodiversity ; Humans ; *Models, Animal ; Regeneration/*physiology ; Regenerative Medicine/*trends ; *Research Design ; Species Specificity ; }, } @article {pmid29179920, year = {2018}, author = {Gammage, PA and Moraes, CT and Minczuk, M}, title = {Mitochondrial Genome Engineering: The Revolution May Not Be CRISPR-Ized.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {101-110}, pmid = {29179920}, issn = {0168-9525}, support = {MC_U105697135//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Biolistics/methods ; Biological Transport ; *CRISPR-Cas Systems ; DNA, Mitochondrial/*genetics/metabolism ; Dependovirus/genetics/metabolism ; Endodeoxyribonucleases/genetics/metabolism ; Gene Editing/*methods ; Genetic Vectors/chemistry/metabolism ; *Genome, Mitochondrial ; Mammals ; Mitochondria/*genetics/metabolism ; Polyribonucleotide Nucleotidyltransferase/genetics/metabolism ; RNA, Guide/genetics/metabolism ; Transcription Activator-Like Effector Nucleases/genetics/metabolism ; Transcription Factors/genetics/metabolism ; }, abstract = {In recent years mitochondrial DNA (mtDNA) has transitioned to greater prominence across diverse areas of biology and medicine. The recognition of mitochondria as a major biochemical hub, contributions of mitochondrial dysfunction to various diseases, and several high-profile attempts to prevent hereditary mtDNA disease through mitochondrial replacement therapy have roused interest in the organellar genome. Subsequently, attempts to manipulate mtDNA have been galvanized, although with few robust advances and much controversy. Re-engineered protein-only nucleases such as mtZFN and mitoTALEN function effectively in mammalian mitochondria, although efficient delivery of nucleic acids into the organelle remains elusive. Such an achievement, in concert with a mitochondria-adapted CRISPR/Cas9 platform, could prompt a revolution in mitochondrial genome engineering and biological understanding. However, the existence of an endogenous mechanism for nucleic acid import into mammalian mitochondria, a prerequisite for mitochondrial CRISPR/Cas9 gene editing, remains controversial.}, } @article {pmid29179919, year = {2018}, author = {}, title = {How long have you been teaching undergraduate genetics and how have genetics courses changed since you were a student or when you first started teaching?.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {4-7}, doi = {10.1016/j.tig.2017.10.005}, pmid = {29179919}, issn = {0168-9525}, mesh = {*Curriculum ; Genetics/*education/trends ; Humans ; Universities ; }, } @article {pmid29179918, year = {2018}, author = {Kuzminov, A}, title = {When DNA Topology Turns Deadly - RNA Polymerases Dig in Their R-Loops to Stand Their Ground: New Positive and Negative (Super)Twists in the Replication-Transcription Conflict.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {2}, pages = {111-120}, pmid = {29179918}, issn = {0168-9525}, support = {R01 GM073115/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacillus subtilis/genetics/metabolism ; Chromosomes, Bacterial ; *DNA Replication ; DNA, Bacterial/*chemistry/genetics/metabolism ; DNA-Directed RNA Polymerases/*genetics/metabolism ; Escherichia coli/genetics/metabolism ; Humans ; Nucleic Acid Conformation ; RNA, Bacterial/*chemistry/genetics/metabolism ; Ribonuclease H/genetics/metabolism ; *Transcription, Genetic ; }, abstract = {Head-on replication-transcription conflict is especially bitter in bacterial chromosomes, explaining why actively transcribed genes are always co-oriented with replication. The mechanism of this conflict remains unclear, besides the anticipated accumulation of positive supercoils between head-on-conflicting polymerases. Unexpectedly, experiments in bacterial and human cells reveal that head-on replication-transcription conflict induces R-loops, indicating hypernegative supercoiling [(-)sc] in the region - precisely the opposite of that assumed. Further, as a result of these R-loops, both replication and transcription in the affected region permanently stall, so the failure of R-loop removal in RNase H-deficient bacteria becomes lethal. How hyper(-)sc emerges in the middle of a positively supercoiled chromosomal domain is a mystery that requires rethinking of topoisomerase action around polymerases.}, } @article {pmid29178517, year = {2018}, author = {Bovet, J and Barkat-Defradas, M and Durand, V and Faurie, C and Raymond, M}, title = {Women's attractiveness is linked to expected age at menopause.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {229-238}, doi = {10.1111/jeb.13214}, pmid = {29178517}, issn = {1420-9101}, abstract = {A great number of studies have shown that features linked to immediate fertility explain a large part of the variance in female attractiveness. This is consistent with an evolutionary perspective, as men are expected to prefer females at the age at which fertility peaks (at least for short-term relationships) in order to increase their reproductive success. However, for long-term relationships, a high residual reproductive value (the expected future reproductive output, linked to age at menopause) becomes relevant as well. In that case, young age and late menopause are expected to be preferred by men. However, the extent to which facial features provide cues to the likely age at menopause has never been investigated so far. Here, we show that expected age at menopause is linked to facial attractiveness of young women. As age at menopause is heritable, we used the mother's age at menopause as a proxy for her daughter's expected age of menopause. We found that men judged faces of women with a later expected age at menopause as more attractive than those of women with an earlier expected age at menopause. This result holds when age, cues of immediate fertility and facial ageing were controlled for. Additionally, we found that the expected age at menopause was not correlated with any of the other variables considered (including immediate fertility cues and facial ageing). Our results show the existence of a new correlate of women's facial attractiveness, expected age at menopause, which is independent of immediate fertility cues and facial ageing.}, } @article {pmid29178238, year = {2018}, author = {Grueber, CE and Gray, LJ and Morris, KM and Simpson, SJ and Senior, AM}, title = {Intergenerational effects of nutrition on immunity: a systematic review and meta-analysis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1108-1124}, doi = {10.1111/brv.12387}, pmid = {29178238}, issn = {1469-185X}, abstract = {Diet and immunity are both highly complex processes through which organisms interact with their environment and adapt to variable conditions. Parents that are able to transmit information to their offspring about prevailing environmental conditions have a selective advantage by 'priming' the physiology of their offspring. We used a meta-analytic approach to test the effect of parental diet on offspring immune responses. Using the geometric framework for nutrition (a method for analysing diet compositions wherein food nutrient components are expressed as axes in a Cartesian coordinate space) to define dietary manipulations in terms of their energy and macronutrient compositions, we compiled the results of 226 experiments from 38 published papers on the intergenerational effects of diet on immunity, across a range of study species and immunological responses. We observed intergenerational impacts of parental nutrition on a number of offspring immunological processes, including expression of pro-inflammatory biomarkers as well as decreases in anti-inflammatory markers in response to certain parental diets. For example, across our data set as a whole (encompassing several types of dietary manipulation), dietary stress in parents was seen to significantly increase pro-inflammatory cytokine levels measured in offspring (overall d = 0.575). All studies included in our analysis were from experiments in which the offspring were raised on a normal or control diet, so our findings suggest that a nutrition-dependent immune state can be inherited, and that this immune state is maintained in the short term, despite offspring returning to an 'optimal' diet. We demonstrate how the geometric framework for nutrition can be used to disentangle the role that different forms of dietary manipulation can have on intergenerational immunity. For example, offspring B-cell responses were significantly decreased when parents were raised on a range of different diets. Similarly, our approach allowed us to show that a parental diet elevated in protein (regardless of energy composition and relative to a control diet) can increase expression of inflammatory markers while decreasing B-cell-associated markers. By conducting a systematic review of the literature, we have identified important gaps that impair our understanding of the intergenerational effects of diet, such as a paucity of experimental studies involving increased protein and decreased energy, and a lack of studies directed at the whole-organism consequences of these processes, such as immune resilience to infection. The results of our analyses inform our understanding of the effects of diet on physiological state across diverse biological fields, including biomedical sciences, maintenance of agricultural breed stock and conservation breeding programs, among others.}, } @article {pmid29178128, year = {2018}, author = {Huang, D and Goldberg, EE and Chou, LM and Roy, K}, title = {The origin and evolution of coral species richness in a marine biodiversity hotspot.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {288-302}, doi = {10.1111/evo.13402}, pmid = {29178128}, issn = {1558-5646}, abstract = {The Coral Triangle (CT) region of the Indo-Pacific realm harbors an extraordinary number of species, with richness decreasing away from this biodiversity hotspot. Despite multiple competing hypotheses, the dynamics underlying this regional diversity pattern remain poorly understood. Here, we use a time-calibrated evolutionary tree of living reef coral species, their current geographic ranges, and model-based estimates of regional rates of speciation, extinction, and geographic range shifts to show that origination rates within the CT are lower than in surrounding regions, a result inconsistent with the long-standing center of origin hypothesis. Furthermore, endemism of coral species in the CT is low, and the CT endemics are older than relatives found outside this region. Overall, our model results suggest that the high diversity of reef corals in the CT is largely due to range expansions into this region of species that evolved elsewhere. These findings strongly support the notion that geographic range shifts play a critical role in generating species diversity gradients. They also show that preserving the processes that gave rise to the striking diversity of corals in the CT requires protecting not just reefs within the hotspot, but also those in the surrounding areas.}, } @article {pmid29177513, year = {2018}, author = {Wu, P and Yan, J and Lai, YC and Ng, CS and Li, A and Jiang, X and Elsey, RM and Widelitz, R and Bajpai, R and Li, WH and Chuong, CM}, title = {Multiple Regulatory Modules Are Required for Scale-to-Feather Conversion.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {417-430}, pmid = {29177513}, issn = {1537-1719}, support = {R01 AR047364/AR/NIAMS NIH HHS/United States ; R01 AR060306/AR/NIAMS NIH HHS/United States ; }, abstract = {The origin of feathers is an important question in Evo-Devo studies, with the eventual evolution of vaned feathers which are aerodynamic, allowing feathered dinosaurs and early birds to fly and venture into new ecological niches. Studying how feathers and scales are developmentally specified provides insight into how a new organ may evolve. We identified feather-associated genes using genomic analyses. The candidate genes were tested by expressing them in chicken and alligator scale forming regions. Ectopic expression of these genes induced intermediate morphotypes between scales and feathers which revealed several major morphogenetic events along this path: Localized growth zone formation, follicle invagination, epithelial branching, feather keratin differentiation, and dermal papilla formation. In addition to molecules known to induce feathers on scales (retinoic acid, β-catenin), we identified novel scale-feather converters (Sox2, Zic1, Grem1, Spry2, Sox18) which induce one or more regulatory modules guiding these morphogenetic events. Some morphotypes resemble filamentous appendages found in feathered dinosaur fossils, whereas others exhibit characteristics of modern avian feathers. We propose these morpho-regulatory modules were used to diversify archosaur scales and to initiate feather evolution. The regulatory combination and hierarchical integration may have led to the formation of extant feather forms. Our study highlights the importance of integrating discoveries between developmental biology and paleontology.}, } @article {pmid29177474, year = {2018}, author = {Zhou, X and Shen, XX and Hittinger, CT and Rokas, A}, title = {Evaluating Fast Maximum Likelihood-Based Phylogenetic Programs Using Empirical Phylogenomic Data Sets.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {486-503}, pmid = {29177474}, issn = {1537-1719}, abstract = {The sizes of the data matrices assembled to resolve branches of the tree of life have increased dramatically, motivating the development of programs for fast, yet accurate, inference. For example, several different fast programs have been developed in the very popular maximum likelihood framework, including RAxML/ExaML, PhyML, IQ-TREE, and FastTree. Although these programs are widely used, a systematic evaluation and comparison of their performance using empirical genome-scale data matrices has so far been lacking. To address this question, we evaluated these four programs on 19 empirical phylogenomic data sets with hundreds to thousands of genes and up to 200 taxa with respect to likelihood maximization, tree topology, and computational speed. For single-gene tree inference, we found that the more exhaustive and slower strategies (ten searches per alignment) outperformed faster strategies (one tree search per alignment) using RAxML, PhyML, or IQ-TREE. Interestingly, single-gene trees inferred by the three programs yielded comparable coalescent-based species tree estimations. For concatenation-based species tree inference, IQ-TREE consistently achieved the best-observed likelihoods for all data sets, and RAxML/ExaML was a close second. In contrast, PhyML often failed to complete concatenation-based analyses, whereas FastTree was the fastest but generated lower likelihood values and more dissimilar tree topologies in both types of analyses. Finally, data matrix properties, such as the number of taxa and the strength of phylogenetic signal, sometimes substantially influenced the programs' relative performance. Our results provide real-world gene and species tree phylogenetic inference benchmarks to inform the design and execution of large-scale phylogenomic data analyses.}, } @article {pmid29177456, year = {2018}, author = {Bitar, M and Barry, G}, title = {Multiple Innovations in Genetic and Epigenetic Mechanisms Cooperate to Underpin Human Brain Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {263-268}, doi = {10.1093/molbev/msx303}, pmid = {29177456}, issn = {1537-1719}, abstract = {Our knowledge of how the human brain differs from those of other species in terms of evolutionary adaptations and functionality is limited. Comparative genomics reveal valuable insight, especially the expansion of human-specific noncoding regulatory and repeat-containing regions. Recent studies add to our knowledge of evolving brain function by investigating cellular mechanisms such as protein emergence, extensive sequence editing, retrotransposon activity, dynamic epigenetic modifications, and multiple noncoding RNA functions. These findings present an opportunity to combine newly discovered genetic and epigenetic mechanisms with more established concepts into a more comprehensive picture to better understand the uniquely evolved human brain.}, } @article {pmid29177446, year = {2018}, author = {Martin, WF and Bryant, DA and Beatty, JT}, title = {A physiological perspective on the origin and evolution of photosynthesis.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {2}, pages = {205-231}, pmid = {29177446}, issn = {1574-6976}, mesh = {Archaea/physiology ; *Biological Evolution ; Cyanobacteria/physiology ; Photosynthesis/*physiology ; Pigments, Biological/metabolism ; }, abstract = {The origin and early evolution of photosynthesis are reviewed from an ecophysiological perspective. Earth's first ecosystems were chemotrophic, fueled by geological H2 at hydrothermal vents and, required flavin-based electron bifurcation to reduce ferredoxin for CO2 fixation. Chlorophyll-based phototrophy (chlorophototrophy) allowed autotrophs to generate reduced ferredoxin without electron bifurcation, providing them access to reductants other than H2. Because high-intensity, short-wavelength electromagnetic radiation at Earth's surface would have been damaging for the first chlorophyll (Chl)-containing cells, photosynthesis probably arose at hydrothermal vents under low-intensity, long-wavelength geothermal light. The first photochemically active pigments were possibly Zn-tetrapyrroles. We suggest that (i) after the evolution of red-absorbing Chl-like pigments, the first light-driven electron transport chains reduced ferredoxin via a type-1 reaction center (RC) progenitor with electrons from H2S; (ii) photothioautotrophy, first with one RC and then with two, was the bridge between H2-dependent chemolithoautotrophy and water-splitting photosynthesis; (iii) photothiotrophy sustained primary production in the photic zone of Archean oceans; (iv) photosynthesis arose in an anoxygenic cyanobacterial progenitor; (v) Chl a is the ancestral Chl; and (vi), anoxygenic chlorophototrophic lineages characterized so far acquired, by horizontal gene transfer, RCs and Chl biosynthesis with or without autotrophy, from the architects of chlorophototrophy-the cyanobacterial lineage.}, } @article {pmid29176606, year = {2018}, author = {Wrighton, KH}, title = {Synthetic biology: Multiplex genome engineering in eukaryotes.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {6-7}, pmid = {29176606}, issn = {1471-0064}, } @article {pmid29176586, year = {2018}, author = {Hofer, U}, title = {Environmental microbiology: Around the globe in 2.2 billion sequences.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {3}, pmid = {29176586}, issn = {1740-1534}, } @article {pmid29176585, year = {2018}, author = {Eme, L and Spang, A and Lombard, J and Stairs, CW and Ettema, TJG}, title = {Archaea and the origin of eukaryotes.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {120}, pmid = {29176585}, issn = {1740-1534}, abstract = {This corrects the article DOI: 10.1038/nrmicro.2017.133.}, } @article {pmid29176584, year = {2018}, author = {Hofer, U}, title = {Parasite development: The missing link to Plasmodium gametocytogenesis.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {3}, pmid = {29176584}, issn = {1740-1534}, } @article {pmid29176583, year = {2018}, author = {Hofer, U}, title = {Bacterial Physiology: Touching base on bacterial surface sensing.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {3}, pmid = {29176583}, issn = {1740-1534}, } @article {pmid29176582, year = {2018}, author = {Radoshevich, L and Cossart, P}, title = {Listeria monocytogenes: towards a complete picture of its physiology and pathogenesis.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {32-46}, pmid = {29176582}, issn = {1740-1534}, mesh = {Animals ; *Host-Pathogen Interactions/genetics/immunology ; Humans ; Listeria monocytogenes/pathogenicity/*physiology ; Listeriosis/*etiology/metabolism ; Virulence ; Virulence Factors ; }, abstract = {Listeria monocytogenes is a food-borne pathogen responsible for a disease called listeriosis, which is potentially lethal in immunocompromised individuals. This bacterium, first used as a model to study cell-mediated immunity, has emerged over the past 20 years as a paradigm in infection biology, cell biology and fundamental microbiology. In this Review, we highlight recent advances in the understanding of human listeriosis and L. monocytogenes biology. We describe unsuspected modes of hijacking host cell biology, ranging from changes in organelle morphology to direct effects on host transcription via a new class of bacterial effectors called nucleomodulins. We then discuss advances in understanding infection in vivo, including the discovery of tissue-specific virulence factors and the 'arms race' among bacteria competing for a niche in the microbiota. Finally, we describe the complexity of bacterial regulation and physiology, incorporating new insights into the mechanisms of action of a series of riboregulators that are critical for efficient metabolic regulation, antibiotic resistance and interspecies competition.}, } @article {pmid29176581, year = {2018}, author = {Husnik, F and McCutcheon, JP}, title = {Functional horizontal gene transfer from bacteria to eukaryotes.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {67-79}, pmid = {29176581}, issn = {1740-1534}, abstract = {Bacteria influence eukaryotic biology as parasitic, commensal or beneficial symbionts. Aside from these organismal interactions, bacteria have also been important sources of new genetic sequences through horizontal gene transfer (HGT) for eukaryotes. In this Review, we focus on gene transfers from bacteria to eukaryotes, discuss how horizontally transferred genes become functional and explore what functions are endowed upon a broad diversity of eukaryotes by genes derived from bacteria. We classify HGT events into two broad types: those that maintain pre-existing functions and those that provide the recipient with new functionality, including altered host nutrition, protection and adaptation to extreme environments.}, } @article {pmid29175679, year = {2018}, author = {Parthasarathy, R}, title = {Monitoring microbial communities using light sheet fluorescence microscopy.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {31-37}, pmid = {29175679}, issn = {1879-0364}, support = {P01 HD022486/HD/NICHD NIH HHS/United States ; P50 GM098911/GM/NIGMS NIH HHS/United States ; }, mesh = {Biofilms ; Gastrointestinal Microbiome ; Imaging, Three-Dimensional/*instrumentation/methods ; *Light ; *Microbiota ; Microscopy, Fluorescence/instrumentation/*methods ; }, abstract = {Microbes often live in dense, dynamic, multi-species communities whose architecture and function are intimately intertwined. Imaging these complex, three-dimensional ensembles presents considerable technical challenges, however. In this review, I describe light sheet fluorescence microscopy, a technique that enables rapid acquisition of three-dimensional images over large fields of view and over long durations, and I highlight recent applications of this method to microbial systems that include artificial closed ecosystems, bacterial biofilms, and gut microbiota. I comment also on the history of light sheet imaging and the many variants of the method. Light sheet techniques have tremendous potential for illuminating the workings of microbial communities, a potential that is just beginning to be realized.}, } @article {pmid29175546, year = {2018}, author = {Boubli, JP and da Silva, MNF and Rylands, AB and Nash, SD and Bertuol, F and Nunes, M and Mittermeier, RA and Byrne, H and Silva, FE and Röhe, F and Sampaio, I and Schneider, H and Farias, IP and Hrbek, T}, title = {How many pygmy marmoset (Cebuella Gray, 1870) species are there? A taxonomic re-appraisal based on new molecular evidence.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {170-182}, doi = {10.1016/j.ympev.2017.11.010}, pmid = {29175546}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Callithrix/*classification/genetics ; Cytochromes b/classification/genetics/metabolism ; DNA/chemistry/isolation & purification/metabolism ; Likelihood Functions ; Male ; Phenotype ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The pygmy marmoset, Cebuella pygmaea, the smallest of the New World monkeys, has one of the largest geographical distributions of the Amazonian primates. Two forms have been recognized: Cebuella pygmaea pygmaea (Spix, 1823), and C. p. niveiventris Lönnberg, 1940. In this study, we investigated if the separation of pygmy marmosets into these two clades can be corroborated by molecular data. We also examine and compare coloration of the pelage in light of the new molecular results. We analyzed the mtDNA cytochrome b gene and, for the first time for any Neotropical primate, we used a reduced representation genome sequencing approach (ddRADseq) to obtain data for recently collected, geographically representative samples from the Rio Japurá, a northern tributary of the Rio Solimões and from the Javarí, Jutaí, Juruá, Madeira and Purus river basins, all tributaries south of the Solimões. We estimated phylogenies and diversification times under both maximum likelihood and Bayesian inference criteria. Our analysis showed two highly supported clades, with intraclade divergences much smaller than interclade divergences, indicating two species of Cebuella: one from the Rio Japurá and one to the south of Solimões. The interpretation of our results in light of the current taxonomy is not trivial however. Lönnberg stated that the type of Spix's pygmy marmoset (type locality 'near Tabatinga') was obtained from the south of the Solimões, and his description of the distinct niveiventris from Lago Ipixuna, south of the Solimões and several hundred kilometres east of Tabatinga, was based on a comparison with specimens that he determined as typical pygmaea that were from the upper Rio Juruá (south of the Solimões). As such it remains uncertain whether the name pygmaea should be applicable to the pygmy marmosets north of the Rio Solimões (Tabatinga type locality) or south (near Tabatinga but across the Solimões). Finally, our analysis of pelage coloration revealed three phenotypic forms: (1) south of the Rio Solimoes, (2) Eirunepé-Acre, upper Juruá basin; and (3) Japurá. More samples from both sides of Solimões in the region of Tabatinga will be necessary to ascertain the exact type locality for Spix's pygmaea and to resolve the current uncertainties surrounding pygmy marmoset taxonomy.}, } @article {pmid29175095, year = {2018}, author = {Deng, M and Jiang, XL and Hipp, AL and Manos, PS and Hahn, M}, title = {Phylogeny and biogeography of East Asian evergreen oaks (Quercus section Cyclobalanopsis; Fagaceae): Insights into the Cenozoic history of evergreen broad-leaved forests in subtropical Asia.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {170-181}, doi = {10.1016/j.ympev.2017.11.003}, pmid = {29175095}, issn = {1095-9513}, mesh = {Base Sequence ; *Forests ; Fossils ; Genetic Speciation ; Indochina ; Japan ; *Phylogeny ; *Phylogeography ; Quercus/*classification/genetics ; Sequence Analysis, DNA ; Time Factors ; *Tropical Climate ; }, abstract = {The evolutionary history of Quercus section Cyclobalanopsis, a dominant lineage in East Asian evergreen broadleaved forests (EBLFs), has not been comprehensively studied using molecular tools. In this study, we reconstruct the first comprehensive phylogeny of this lineage using a genomic approach (restriction-site associated DNA sequencing, RAD-seq), sampling 35 of the ca. 90 species currently recognized, representing all main morphological groups of section Cyclobalanopsis. In addition, 10 other species of Quercus and two outgroups were also sampled. Divergence times were estimated using a relaxed clock model and two fossil calibrations. Ancestral areas and dispersal routes were inferred using statistical dispersal-vicariance analysis and the dispersal-extinction-cladogenesis (DEC) model. The phylogeny of Quercus section Cyclobalanopsis demonstrates the section to be monophyletic, comprising two main lineages and six subclades that are well supported by anatomical traits. Biogeographical reconstructions indicate that the wide northern hemisphere distribution of Quercus was disrupted in the Late Eocene, leading to the main extant groups at about 33 Ma. The earliest divergences in section Cyclobalanopsis correspond to the phased uplift of the Himalayas and lateral extrusion of Indochina at the transition of the Oligocene and Miocene, where the highest rate of diversification occurred in the late Miocene. Dispersal from Sino-Himalaya and the Palaeotropics to Sino-Japan in the Miocene was facilitated by the increased intensity of East Asian summer monsoons and by the Middle Miocene Climatic Optimum. Our results highlight the importance of climatic changes and Indo-Eurasian collision-induced tectonic activities from the Neogene onward to the spatial-temporal diversification patterns of Asian EBLF lineages.}, } @article {pmid29174610, year = {2018}, author = {Galal, L and Ajzenberg, D and Hamidović, A and Durieux, MF and Dardé, ML and Mercier, A}, title = {Toxoplasma and Africa: One Parasite, Two Opposite Population Structures.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {140-154}, doi = {10.1016/j.pt.2017.10.010}, pmid = {29174610}, issn = {1471-5007}, mesh = {Africa/epidemiology ; Animals ; Demography ; *Genetic Variation ; Toxoplasma/classification/*genetics ; Toxoplasmosis/epidemiology/parasitology ; }, abstract = {Exploring the genetic diversity of Toxoplasma gondii is essential for an understanding of its worldwide distribution and the determinants of its evolution. Africa remains one of the least studied areas of the world regarding T. gondii genetic diversity. This review has compiled published data on T. gondii strains from Africa to generate a comprehensive map of their continent-wide geographical distribution. The emerging picture about T. gondii strain distribution in Africa suggests a geographical separation of the parasite populations across the continent. We discuss the potential role of a number of factors in shaping this structure. We finally suggest the next steps towards a better understanding of Toxoplasma epidemiology in Africa in light of the strains circulating on this continent.}, } @article {pmid29174414, year = {2018}, author = {Ruff, CB and Niskanen, M}, title = {Introduction to special issue: Body mass estimation - Methodological issues and fossil applications.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {1-7}, doi = {10.1016/j.jhevol.2017.09.011}, pmid = {29174414}, issn = {1095-8606}, } @article {pmid29174373, year = {2018}, author = {}, title = {Sara Lustigman: Developing a vaccine to accelerate onchocerciasis elimination.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {1-3}, doi = {10.1016/j.pt.2017.11.001}, pmid = {29174373}, issn = {1471-5007}, mesh = {Africa/epidemiology ; *Disease Eradication ; Humans ; New York ; Onchocerciasis/epidemiology/immunology/*prevention & control ; *Vaccines/economics ; }, } @article {pmid29174224, year = {2018}, author = {Ward, JD}, title = {Spotlight on CRISPR in Strongyloides Parasitic Nematodes.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {6-9}, pmid = {29174224}, issn = {1471-5007}, support = {R00 GM107345/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Gene Editing ; *Strongyloides ; }, abstract = {Parasitic nematodes are biomedically and economically important, but many are genetically intractable which limits our understanding of their molecular and cellular biology. Gang et al. report CRISPR/Cas9 genome editing in parasites of the genus Strongyloides, generating both knock-outs and knock-ins, and demonstrated heritability of the modifications, a crucial advance in the field.}, } @article {pmid29174223, year = {2018}, author = {Miró, G and Petersen, C and Cardoso, L and Bourdeau, P and Baneth, G and Solano-Gallego, L and Pennisi, MG and Ferrer, L and Oliva, G}, title = {Novel Areas for Prevention and Control of Canine Leishmaniosis: (Trends in Parasitology 33, 718-730; 2017).}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {445}, doi = {10.1016/j.pt.2017.11.003}, pmid = {29174223}, issn = {1471-5007}, } @article {pmid29174101, year = {2018}, author = {Jamet, A and Charbit, A and Nassif, X}, title = {Antibacterial Toxins: Gram-Positive Bacteria Strike Back!.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {89-91}, doi = {10.1016/j.tim.2017.11.003}, pmid = {29174101}, issn = {1878-4380}, mesh = {Anti-Bacterial Agents/*metabolism ; Bacterial Proteins/metabolism ; Bacterial Secretion Systems/metabolism ; Bacterial Toxins/*metabolism ; Gram-Negative Bacteria/metabolism ; Gram-Positive Bacteria/*metabolism ; Protein Domains ; Virulence Factors ; }, abstract = {Bacteria live in communities where strains compete with each other by deploying an arsenal of antibacterial toxins. While the past decade revealed the vast array of antibacterial toxins secreted by Gram-negative bacteria, several recent studies have begun to uncover the ability of Gram-positive bacteria to battle with their own weapons.}, } @article {pmid29174100, year = {2018}, author = {Meysman, FJR}, title = {Cable Bacteria Take a New Breath Using Long-Distance Electricity.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {411-422}, doi = {10.1016/j.tim.2017.10.011}, pmid = {29174100}, issn = {1878-4380}, mesh = {Bacteria/*chemistry ; *Electricity ; *Electron Transport ; Electrons ; Environmental Microbiology ; Geologic Sediments ; Oxidation-Reduction ; Oxygen/metabolism ; Sulfides/metabolism ; Sulfur/metabolism ; }, abstract = {Recently, a new group of multicellular microorganisms was discovered, called 'cable bacteria', which are capable of generating and mediating electrical currents across centimetre-scale distances. By transporting electrons from cell to cell, cable bacteria can harvest electron donors and electron acceptors that are widely separated in space, thus providing them with a competitive advantage for survival in aquatic sediments. The underlying process of long-distance electron transport challenges some long-held ideas about the energy metabolism of multicellular organisms and entails a whole new type of electrical cooperation between cells. This review summarizes the current knowledge about these intriguing multicellular bacteria.}, } @article {pmid29173900, year = {2018}, author = {Hobbs, RJ and Valentine, LE and Standish, RJ and Jackson, ST}, title = {Movers and Stayers: Novel Assemblages in Changing Environments.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {2}, pages = {116-128}, doi = {10.1016/j.tree.2017.11.001}, pmid = {29173900}, issn = {1872-8383}, mesh = {*Animal Distribution ; *Biodiversity ; *Climate Change ; Conservation of Natural Resources/*methods ; Ecosystem ; *Plant Dispersal ; }, abstract = {Increased attention to species movement in response to environmental change highlights the need to consider changes in species distributions and altered biological assemblages. Such changes are well known from paleoecological studies, but have accelerated with ongoing pervasive human influence. In addition to species that move, some species will stay put, leading to an array of novel interactions. Species show a variety of responses that can allow movement or persistence. Conservation and restoration actions have traditionally focused on maintaining or returning species in particular places, but increasingly also include interventions that facilitate movement. Approaches are required that incorporate the fluidity of biotic assemblages into the goals set and interventions deployed.}, } @article {pmid29173869, year = {2018}, author = {Heintz-Buschart, A and Wilmes, P}, title = {Human Gut Microbiome: Function Matters.}, journal = {Trends in microbiology}, volume = {26}, number = {7}, pages = {563-574}, doi = {10.1016/j.tim.2017.11.002}, pmid = {29173869}, issn = {1878-4380}, abstract = {The human gut microbiome represents a complex ecosystem contributing essential functions to its host. Recent large-scale metagenomic studies have provided insights into its structure and functional potential. However, the functional repertoire which is actually contributed to human physiology remains largely unexplored. Here, by leveraging recent omics datasets, we challenge current assumptions regarding key attributes of the functional gut microbiome, in particular with respect to its variability. We further argue that the closing of existing gaps in functional knowledge should be addressed by a most-wanted gene list, the development and application of molecular and cellular high-throughput measurements, the development and sensible use of experimental models, as well as the direct study of observable molecular effects in the human host.}, } @article {pmid29173868, year = {2018}, author = {Vijayan, A and Rumbo, M and Carnoy, C and Sirard, JC}, title = {Compartmentalized Antimicrobial Defenses in Response to Flagellin.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {423-435}, doi = {10.1016/j.tim.2017.10.008}, pmid = {29173868}, issn = {1878-4380}, mesh = {Adaptive Immunity ; Anti-Infective Agents/metabolism/*pharmacology ; Bacteria/*immunology/pathogenicity ; Dendritic Cells/immunology ; Epithelial Cells/immunology ; Flagellin/*immunology ; Immunity, Innate ; Interleukins/metabolism ; Lymphocytes/immunology ; Toll-Like Receptor 5/metabolism ; }, abstract = {Motility is often a pathogenicity determinant of bacteria targeting mucosal tissues. Flagella constitute the machinery that propels bacteria into appropriate niches. Besides motility, the structural component, flagellin, which forms the flagella, targets Toll-like receptor 5 (TLR5) to activate innate immunity. The compartmentalization of flagellin-mediated immunity and the contribution of epithelial cells and dendritic cells in detecting flagellin within luminal and basal sides are highlighted here, respectively. While a direct stimulation of the epithelium mainly results in recruitment of immune cells and production of antimicrobial molecules, TLR5 engagement on parenchymal dendritic cells can contribute to the stimulation of innate lymphocytes such as type 3 innate lymphoid cells, as well as T helper cells. This review, therefore, illustrates how the innate and adaptive immunity to flagellin are differentially regulated by the epithelium and the dendritic cells in response to pathogens that either colonize or invade mucosa.}, } @article {pmid29172233, year = {2018}, author = {Tian, R and Xu, S and Chai, S and Yin, D and Zakon, H and Yang, G}, title = {Stronger selective constraint on downstream genes in the oxidative phosphorylation pathway of cetaceans.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {217-228}, doi = {10.1111/jeb.13213}, pmid = {29172233}, issn = {1420-9101}, abstract = {The oxidative phosphorylation (OXPHOS) pathway is an efficient way to produce energy via adenosine triphosphate (ATP), which is critical for sustaining an energy supply for cetaceans in a hypoxic environment. Several studies have shown that natural selection may shape the evolution of the genes involved in OXPHOS. However, how network architecture drives OXPHOS protein sequence evolution remains poorly explored. Here, we investigated the evolutionary patterns of genes in the OXPHOS pathway across six cetacean genomes within the framework of a functional network. Our results show a negative correlation between the strength of purifying selection and pathway position. This result indicates that downstream genes were subjected to stronger evolutionary constraints than upstream genes, which may be due to the dual function of ATP synthase in the OXPHOS pathway. Additionally, there was a positive correlation between codon usage bias and omega (ω = dN/dS) and a negative correlation with synonymous substitution rate (dS), indicating that the stronger selective constraint on genes (with less biased codon usage) along the OXPHOS pathway is attributable to an increase in the rate of synonymous substitution. Surprisingly, there was no significant correlation between protein-protein interactions and the evolutionary estimates, implying that highly connected enzymes may not always show greater evolutionary constraints. Compared with that observed for terrestrial mammals, we found that the signature of positive selection detected in five genes (ATP5J, LHPP, PPA1, UQCRC1 and UQCRQ) was cetacean-specific, reflecting the importance of OXPHOS for survival in hypoxic, aquatic environments.}, } @article {pmid29170278, year = {2018}, author = {Kabeche, L and Nguyen, HD and Buisson, R and Zou, L}, title = {A mitosis-specific and R loop-driven ATR pathway promotes faithful chromosome segregation.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {108-114}, pmid = {29170278}, issn = {1095-9203}, support = {K99 CA212154/CA/NCI NIH HHS/United States ; T32 CA009216/CA/NCI NIH HHS/United States ; R01 GM076388/GM/NIGMS NIH HHS/United States ; R01 CA197779/CA/NCI NIH HHS/United States ; T32 DK007540/DK/NIDDK NIH HHS/United States ; }, mesh = {Ataxia Telangiectasia Mutated Proteins/genetics/metabolism ; Aurora Kinase A/metabolism ; Cell Line, Tumor ; Centromere/*enzymology ; Checkpoint Kinase 1/metabolism ; Chromosomal Proteins, Non-Histone/metabolism ; Chromosome Segregation/*genetics ; Humans ; Microfilament Proteins/metabolism ; Mitosis/*genetics ; }, abstract = {The ataxia telangiectasia mutated and Rad3-related (ATR) kinase is crucial for DNA damage and replication stress responses. Here, we describe an unexpected role of ATR in mitosis. Acute inhibition or degradation of ATR in mitosis induces whole-chromosome missegregation. The effect of ATR ablation is not due to altered cyclin-dependent kinase 1 (CDK1) activity, DNA damage responses, or unscheduled DNA synthesis but to loss of an ATR function at centromeres. In mitosis, ATR localizes to centromeres through Aurora A-regulated association with centromere protein F (CENP-F), allowing ATR to engage replication protein A (RPA)-coated centromeric R loops. As ATR is activated at centromeres, it stimulates Aurora B through Chk1, preventing formation of lagging chromosomes. Thus, a mitosis-specific and R loop-driven ATR pathway acts at centromeres to promote faithful chromosome segregation, revealing functions of R loops and ATR in suppressing chromosome instability.}, } @article {pmid29170277, year = {2018}, author = {Lamichhaney, S and Han, F and Webster, MT and Andersson, L and Grant, BR and Grant, PR}, title = {Rapid hybrid speciation in Darwin's finches.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6372}, pages = {224-228}, doi = {10.1126/science.aao4593}, pmid = {29170277}, issn = {1095-9203}, mesh = {Animals ; Beak/anatomy & histology ; Breeding ; Ecosystem ; Ecuador ; Female ; Finches/anatomy & histology/*genetics/physiology ; *Genetic Speciation ; Homozygote ; Hybridization, Genetic ; Male ; Phylogeny ; *Reproductive Isolation ; Selection, Genetic ; Time Factors ; }, abstract = {Homoploid hybrid speciation in animals has been inferred frequently from patterns of variation, but few examples have withstood critical scrutiny. Here we report a directly documented example, from its origin to reproductive isolation. An immigrant Darwin's finch to Daphne Major in the Galápagos archipelago initiated a new genetic lineage by breeding with a resident finch (Geospiza fortis). Genome sequencing of the immigrant identified it as a G. conirostris male that originated on Española >100 kilometers from Daphne Major. From the second generation onward, the lineage bred endogamously and, despite intense inbreeding, was ecologically successful and showed transgressive segregation of bill morphology. This example shows that reproductive isolation, which typically develops over hundreds of generations, can be established in only three.}, } @article {pmid29169681, year = {2018}, author = {VanSickle, C and Cofran, Z and García-Martínez, D and Williams, SA and Churchill, SE and Berger, LR and Hawks, J}, title = {Homo naledi pelvic remains from the Dinaledi Chamber, South Africa.}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {122-136}, doi = {10.1016/j.jhevol.2017.10.001}, pmid = {29169681}, issn = {1095-8606}, abstract = {In the hominin fossil record, pelvic remains are sparse and are difficult to attribute taxonomically when they are not directly associated with craniodental material. Here we describe the pelvic remains from the Dinaledi Chamber in the Rising Star cave system, Cradle of Humankind, South Africa, which has produced hominin fossils of a new species, Homo naledi. Though this species has been attributed to Homo based on cranial and lower limb morphology, the morphology of some of the fragmentary pelvic remains recovered align more closely with specimens attributed to the species Australopithecus afarensis and Australopithecus africanus than they do with those of most (but not all) known species of the genus Homo. As with A. afarensis and A. africanus, H. naledi appears to have had marked lateral iliac flare and either a weakly developed or non-existent acetabulocristal buttress or a distinct, albeit weakly developed, acetabulospinous buttress. At the same time, H. naledi has robust superior pubic and ischiopubic rami and a short ischium with a narrow tuberoacetabular sulcus, similar to those found in modern humans. The fragmentary nature of the Dinaledi pelvic assemblage makes the attribution of sex and developmental age to individual specimens difficult, which in turn diminishes our ability to identify the number of individuals represented in the assemblage. At present, we can only confidently say that the pelvic fossils from Rising Star represent at least four individuals based on the presence of four overlapping right ischial fossils (whereas a minimum of 15 individuals can be identified from the Dinaledi dental assemblage). A primitive, early Australopithecus-like false pelvis combined with a derived Homo-like true pelvis is morphologically consistent with evidence from the lower ribcage and proximal femur of H. naledi. The overall similarity of H. naledi ilia to those of australopiths supports the inference, drawn from the observation of primitive pelvic morphology in the extinct species Homo floresiensis, that there is substantial variation in pelvic form within the genus Homo. In the light of these findings, we urge caution in making taxonomic attributions-even at the genus level-of isolated fossil ossa coxae.}, } @article {pmid29169680, year = {2018}, author = {Arroyo, A and de la Torre, I}, title = {Pounding tools in HWK EE and EF-HR (Olduvai Gorge, Tanzania): Percussive activities in the Oldowan-Acheulean transition.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {402-421}, doi = {10.1016/j.jhevol.2017.10.005}, pmid = {29169680}, issn = {1095-8606}, abstract = {In this paper, we present pounded objects from excavations at HWK EE and EF-HR, which are studied from macro and microscopic perspectives. Analysis of HWK EE revealed one of the largest collections of percussive objects from Olduvai Gorge, while excavations at EF-HR have allowed us to recover a much wider collection of percussive tools than previously recorded. Differences are observed between the two localities. At the Acheulean site of EF-HR, percussive tools were predominantly used in the production of flakes and large cutting tools (LCTs). At the Oldowan site of HWK EE, the tool repertoire probably related to a wider range of activities, including bone breaking and bipolar knapping. Comparison of these two assemblages, potentially produced by different hominin species, helps provide a wider picture of pounding activities during the Oldowan-Acheulean transition at Olduvai Gorge.}, } @article {pmid29169679, year = {2018}, author = {Young, M and Johannesdottir, F and Poole, K and Shaw, C and Stock, JT}, title = {Assessing the accuracy of body mass estimation equations from pelvic and femoral variables among modern British women of known mass.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {130-139}, doi = {10.1016/j.jhevol.2017.10.011}, pmid = {29169679}, issn = {1095-8606}, abstract = {Femoral head diameter is commonly used to estimate body mass from the skeleton. The three most frequently employed methods, designed by Ruff, Grine, and McHenry, were developed using different populations to address different research questions. They were not specifically designed for application to female remains, and their accuracy for this purpose has rarely been assessed or compared in living populations. This study analyzes the accuracy of these methods using a sample of modern British women through the use of pelvic CT scans (n = 97) and corresponding information about the individuals' known height and weight. Results showed that all methods provided reasonably accurate body mass estimates (average percent prediction errors under 20%) for the normal weight and overweight subsamples, but were inaccurate for the obese and underweight subsamples (average percent prediction errors over 20%). When women of all body mass categories were combined, the methods provided reasonable estimates (average percent prediction errors between 16 and 18%). The results demonstrate that different methods provide more accurate results within specific body mass index (BMI) ranges. The McHenry Equation provided the most accurate estimation for women of small body size, while the original Ruff Equation is most likely to be accurate if the individual was obese or severely obese. The refined Ruff Equation was the most accurate predictor of body mass on average for the entire sample, indicating that it should be utilized when there is no knowledge of the individual's body size or if the individual is assumed to be of a normal body size. The study also revealed a correlation between pubis length and body mass, and an equation for body mass estimation using pubis length was accurate in a dummy sample, suggesting that pubis length can also be used to acquire reliable body mass estimates. This has implications for how we interpret body mass in fossil hominins and has particular relevance to the interpretation of the long pubic ramus that is characteristic of Neandertals.}, } @article {pmid29169146, year = {2018}, author = {Leon, LM and Mendoza, SD and Bondy-Denomy, J}, title = {How bacteria control the CRISPR-Cas arsenal.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {87-95}, pmid = {29169146}, issn = {1879-0364}, support = {DP5 OD021344/OD/NIH HHS/United States ; T32 GM007810/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/enzymology/*genetics/immunology ; Bacteriophages/genetics ; CRISPR-Cas Systems/*genetics/immunology ; Clustered Regularly Interspaced Short Palindromic Repeats/genetics ; Deoxyribonucleases/genetics/metabolism ; Gene Expression Regulation, Bacterial/*immunology ; }, abstract = {CRISPR-Cas systems are adaptive immune systems that protect their hosts from predation by bacteriophages (phages) and parasitism by other mobile genetic elements (MGEs). Given the potent nuclease activity of CRISPR effectors, these enzymes must be carefully regulated to minimize toxicity and maximize anti-phage immunity. While attention has been given to the transcriptional regulation of these systems (reviewed in [1]), less consideration has been given to the crucial post-translational processes that govern enzyme activation and inactivation. Here, we review recent findings that describe how Cas nucleases are controlled in diverse systems to provide a robust anti-viral response while limiting auto-immunity. We also draw comparisons to a distinct bacterial immune system, restriction-modification.}, } @article {pmid29169058, year = {2018}, author = {Devaux, L and Kaminski, PA and Trieu-Cuot, P and Firon, A}, title = {Cyclic di-AMP in host-pathogen interactions.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {21-28}, doi = {10.1016/j.mib.2017.11.007}, pmid = {29169058}, issn = {1879-0364}, mesh = {Animals ; Bacteria/growth & development/immunology/*metabolism/pathogenicity ; Cyclic AMP/biosynthesis/*metabolism ; Host-Pathogen Interactions/immunology/*physiology ; Humans ; Immunity, Innate ; Macrophages/immunology ; Membrane Proteins/genetics/metabolism ; Mice ; Nucleotidyltransferases/metabolism ; Signal Transduction/immunology/physiology ; }, abstract = {Cyclic di-AMP (c-di-AMP) is a bacterial signaling nucleotide synthesized by several human pathogens. This widespread and specific bacterial product is recognized by infected host cells to trigger an innate immune response. Detection of c-di-AMP in the host cytosol leads primarily to the induction of type I interferon via the STING-cGAS signaling axis, while being also entangled in the activation of the NF-κB pathway. During their long-standing interaction, host and pathogens have co-evolved to control c-di-AMP activation of innate immunity. On the bacterial side, the quantity of c-di-AMP released inside cells allows to manipulate the host response to exacerbate infection by avoiding immune recognition or, at the opposite, by overloading the STING-cGAS pathway.}, } @article {pmid29168309, year = {2018}, author = {Wu, T and Dhami, GK and Thompson, GJ}, title = {Soldier-biased gene expression in a subterranean termite implies functional specialization of the defensive caste.}, journal = {Evolution & development}, volume = {20}, number = {1}, pages = {3-16}, doi = {10.1111/ede.12243}, pmid = {29168309}, issn = {1525-142X}, mesh = {Animals ; Computational Biology ; Gene Expression Regulation ; Insect Proteins/*genetics ; Isoptera/classification/*genetics/*physiology ; Life Cycle Stages ; Phenotype ; Reproduction ; Sequence Analysis, DNA ; *Transcriptome ; }, abstract = {In a termite colony, reproduction is typically monopolized by a small number of sexuals that are supported by reproductively altruistic soldiers and workers. We expect caste differentiation to be associated with clear-cut differences in gene expression, and for these differences to reflect caste function and development. Here, we use RNA-Sequencing to compare the gene expression profiles of sexual nymphs and two non-reproductive helper castes (i.e., workers and soldiers) of the Eastern subterranean termite Reticulitermes flavipes. We found that of n = 93 genes that are strictly expressed as a function of caste, a majority (78%) show a soldier-specific pattern. This conspicuous soldier-bias in genome-wide expression suggests that this defensively specialized caste is functionally well-differentiated from both the reproductive and the other non-reproductive caste of this species, despite a shared developmental program with workers. Gene ontology analysis supports the notion of functional specialization by soldiers, as soldier-biased gene sets are enriched for novel biological processes. Whether this pattern reflects ancient or more recent bouts of selection for caste novelty at the gene-regulatory level is not known, but because soldiers are sterile and thus have no direct fitness, any selection for novelty must have been mediated indirectly, through reproducing relatives.}, } @article {pmid29167014, year = {2018}, author = {Junno, JA and Niskanen, M and Maijanen, H and Holt, B and Sladek, V and Niinimäki, S and Berner, M}, title = {The effect of age and body composition on body mass estimation of males using the stature/bi-iliac method.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {122-129}, doi = {10.1016/j.jhevol.2017.10.006}, pmid = {29167014}, issn = {1095-8606}, abstract = {The stature/bi-iliac breadth method provides reasonably precise, skeletal frame size (SFS) based body mass (BM) estimations across adults as a whole. In this study, we examine the potential effects of age changes in anthropometric dimensions on the estimation accuracy of SFS-based body mass estimation. We use anthropometric data from the literature and our own skeletal data from two osteological collections to study effects of age on stature, bi-iliac breadth, body mass, and body composition, as they are major components behind body size and body size estimations. We focus on males, as relevant longitudinal data are based on male study samples. As a general rule, lean body mass (LBM) increases through adolescence and early adulthood until people are aged in their 30s or 40s, and starts to decline in the late 40s or early 50s. Fat mass (FM) tends to increase until the mid-50s and declines thereafter, but in more mobile traditional societies it may decline throughout adult life. Because BM is the sum of LBM and FM, it exhibits a curvilinear age-related pattern in all societies. Skeletal frame size is based on stature and bi-iliac breadth, and both of those dimensions are affected by age. Skeletal frame size based body mass estimation tends to increase throughout adult life in both skeletal and anthropometric samples because an age-related increase in bi-iliac breadth more than compensates for an age-related stature decline commencing in the 30s or 40s. Combined with the above-mentioned curvilinear BM change, this results in curvilinear estimation bias. However, for simulations involving low to moderate percent body fat, the stature/bi-iliac method works well in predicting body mass in younger and middle-aged adults. Such conditions are likely to have applied to most human paleontological and archaeological samples.}, } @article {pmid29166621, year = {2018}, author = {Valentini, M and Gonzalez, D and Mavridou, DA and Filloux, A}, title = {Lifestyle transitions and adaptive pathogenesis of Pseudomonas aeruginosa.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {15-20}, doi = {10.1016/j.mib.2017.11.006}, pmid = {29166621}, issn = {1879-0364}, support = {MR/M009505/1//Medical Research Council/United Kingdom ; BB/N002539/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/L007959/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Animals ; Bacterial Infections/classification/*microbiology ; Bacterial Proteins/metabolism ; Biofilms ; *Gene Expression Regulation, Bacterial ; Host-Pathogen Interactions ; Humans ; Mice ; Pseudomonas aeruginosa/genetics/metabolism/*pathogenicity ; Virulence ; Virulence Factors ; }, abstract = {Pseudomonas aeruginosa acute and chronic infections are of great concern to human health, especially in hospital settings. It is currently assumed that P. aeruginosa has two antagonistic pathogenic strategies that parallel two different lifestyles; free-living cells are predominantly cytotoxic and induce an acute inflammatory reaction, while biofilm-forming communities cause refractory chronic infections. Recent findings suggest that the planktonic-to-sessile transition is a complex, reversible and overall dynamic differentiation process. Here, we examine how the Gac/Rsm regulatory cascade, a key player in this lifestyle switch, endows P. aeruginosa with both a permissive lifecycle in nature and flexible virulence strategy during infection.}, } @article {pmid29166577, year = {2018}, author = {Lupu, FI and Burnett, JB and Eggenschwiler, JT}, title = {Cell cycle-related kinase regulates mammalian eye development through positive and negative regulation of the Hedgehog pathway.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {24-35}, doi = {10.1016/j.ydbio.2017.10.022}, pmid = {29166577}, issn = {1095-564X}, support = {R01 HD050760/HD/NICHD NIH HHS/United States ; T32 GM007103/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Cyclin-Dependent Kinases/genetics/*metabolism ; Embryo, Mammalian/cytology/*embryology ; Eye/cytology/*embryology ; Female ; Hedgehog Proteins/genetics/*metabolism ; Male ; Mice ; Mice, Mutant Strains ; Organogenesis/*physiology ; Signal Transduction/*physiology ; Zinc Finger Protein Gli2/genetics/*metabolism ; }, abstract = {Cell cycle-related kinase (CCRK) is a conserved regulator of ciliogenesis whose loss in mice leads to a wide range of developmental defects, including exencephaly, preaxial polydactyly, skeletal abnormalities, and microphthalmia. Here, we investigate the role of CCRK in mouse eye development. Ccrk mutants show dramatic patterning defects, with an expansion of the optic stalk domain into the optic cup, as well as an expansion of the retinal pigment epithelium (RPE) into neural retina (NR) territory. In addition, Ccrk mutants display a shortened optic stalk. These defects are associated with bimodal changes in Hedgehog (Hh) pathway activity within the eye, including the loss of proximal, high level responses but a gain in distal, low level responses. We simultaneously removed the Hh activator GLI2 in Ccrk mutants (Ccrk-/-;Gli2-/-), which resulted in rescue of optic cup patterning and exacerbation of optic stalk length defects. Next, we disrupted the Hh pathway antagonist GLI3 in mutants lacking CCRK (Ccrk-/-;Gli3-/-), which lead to even greater expansion of the RPE markers into the NR domain and a complete loss of NR specification within the optic cup. These results indicate that CCRK functions in eye development by both positively and negatively regulating the Hh pathway, and they reveal distinct requirements for Hh signaling in patterning and morphogenesis of the eyes.}, } @article {pmid29166128, year = {2018}, author = {Wasternack, C and Feussner, I}, title = {The Oxylipin Pathways: Biochemistry and Function.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {363-386}, doi = {10.1146/annurev-arplant-042817-040440}, pmid = {29166128}, issn = {1545-2123}, abstract = {Plant oxylipins form a constantly growing group of signaling molecules that comprise oxygenated fatty acids and metabolites derived therefrom. In the last decade, the understanding of biosynthesis, metabolism, and action of oxylipins, especially jasmonates, has dramatically improved. Additional mechanistic insights into the action of enzymes and insights into signaling pathways have been deepened for jasmonates. For other oxylipins, such as the hydroxy fatty acids, individual signaling properties and cross talk between different oxylipins or even with additional phytohormones have recently been described. This review summarizes recent understanding of the biosynthesis, regulation, and function of oxylipins.}, } @article {pmid29165628, year = {2018}, author = {Bhardwaj, S and Prudic, KL and Bear, A and Dasgupta, M and Wasik, BR and Tong, X and Cheong, WF and Wenk, MR and Monteiro, A}, title = {Sex Differences in 20-Hydroxyecdysone Hormone Levels Control Sexual Dimorphism in Bicyclus anynana Wing Patterns.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {465-472}, pmid = {29165628}, issn = {1537-1719}, abstract = {In contrast to the important role of hormones in the development of sexual traits in vertebrates (Cox RM, Stenquist DS, Calsbeek R. 2009. Testosterone, growth and the evolution of sexual size dimorphism. J Evol Biol. 22(8):1586-1598.), the differentiation of these traits in insects is attributed almost exclusively to cell-autonomous mechanisms controlled by members of the sex determination pathway (Verhulst EC, van de Zande L. 2015. Double nexus - doublesex is the connecting element in sex determination. Brief Funct Genomics 14(6):396-406.), such as doublesex. Although hormones can shape the development of sexual traits in insects, variation in hormone levels are not conclusively known to cause dimorphism in these traits (Prakash A, Monteiro A. 2016. Molecular mechanisms of secondary sexual trait development in insects. Curr Opin Insect Sci. 17:40-48.). Here, we show that butterflies use sex-specific differences in 20-hydroxyecdysone hormone titers to create sexually dimorphic wing ornaments. Females of the dry season (DS) form of Bicyclus anynana display a larger sexual ornament on their wings than males, whereas in the wet season form both sexes have similarly sized ornaments (Prudic KL, Jeon C, Cao H, Monteiro A. 2011. Developmental plasticity in sexual roles of butterfly species drives mutual sexual ornamentation. Science 331(6013):73-75.). High levels of circulating 20-hydroxyecdysone during larval development in DS females and wet season forms cause proliferation of the cells fated to give rise to this wing ornament, and results in sexual dimorphism in the DS forms. This study advances our understanding of how the environment regulates sex-specific patterns of plasticity of sexual ornaments and conclusively shows that hormones can play a role in the development of secondary sexual traits in insects, just like they do in vertebrates.}, } @article {pmid29165618, year = {2018}, author = {Novakowski, KE and Yap, NVL and Yin, C and Sakamoto, K and Heit, B and Golding, GB and Bowdish, DME}, title = {Human-Specific Mutations and Positively Selected Sites in MARCO Confer Functional Changes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {440-450}, pmid = {29165618}, issn = {1537-1719}, support = {R15 AI094436/AI/NIAID NIH HHS/United States ; MOP-123419//CIHR/Canada ; }, abstract = {Macrophage Receptor with COllagenous structure (MARCO) is a class A scavenger receptor that binds, phagocytoses, and modifies inflammatory responses to bacterial pathogens. Multiple candidate gene approach studies have shown that polymorphisms in MARCO are associated with susceptibility or resistance to Mycobacterium tuberculosis infection, but how these variants alter function is not known. To complement candidate gene approach studies, we previously used phylogenetic analyses to identify a residue, glutamine 452 (Q452), within the ligand-binding Scavenger Receptor Cysteine Rich domain as undergoing positive selection in humans. Herein, we show that Q452 is found in Denisovans, Neanderthals, and extant humans, but all other nonprimate, terrestrial, and aquatic mammals possess an aspartic acid (D452) residue. Further analysis of hominoid sequences of MARCO identified an additional human-specific mutation, phenylalanine 282 (F282), within the collagenous domain. We show that residue 282 is polymorphic in humans, but only 17% of individuals (rs6761637) possess the ancestral serine residue at position 282. We show that rs6761637 is in linkage disequilibrium with MARCO polymorphisms that have been previously linked to susceptibility to pulmonary tuberculosis. To assess the functional importance of sites Q452 and F282 in humans, we cloned the ancestral residues and loss-of-function mutations and investigated the role of these residues in binding and internalizing polystyrene microspheres and Escherichia coli. Herein, we show that the residues at sites 452 and 282 enhance receptor function.}, } @article {pmid29164722, year = {2018}, author = {Somjee, U and Miller, CW and Tatarnic, NJ and Simmons, LW}, title = {Experimental manipulation reveals a trade-off between weapons and testes.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {57-65}, doi = {10.1111/jeb.13193}, pmid = {29164722}, issn = {1420-9101}, mesh = {Animals ; Biological Evolution ; Female ; Hemiptera/*anatomy & histology/*physiology ; Male ; Phenotype ; Selection, Genetic ; Sexual Behavior, Animal/*physiology ; Testis/*anatomy & histology ; }, abstract = {Theory predicts a trade-off between sexually selected weapons used to secure mates and post-copulatory traits used to maximize fertilization success. However, individuals that have a greater capacity to acquire resources from the environment may invest more in both pre- and post-copulatory traits, and trade-offs may not be readily apparent. Here, we manipulate the phenotype of developing individuals to examine allocation trade-offs between weapons and testes in Mictis profana (Hemiptera: Coreidae), a species where the hind legs are sexually selected weapons used in contests over access to females. We experimentally prevented males from developing weapons by inducing them to autotomize their hind legs before the final moult to adulthood. We compared trait expression in this group to males where autotomy was induced in the mid-legs, which are presumably not under sexual selection to the same extent. We found males without weapons invested proportionally more in testes mass than those with their mid-legs removed. Males that developed to adulthood without weapons did not differ from the mid-leg removal group in other traits potentially under precopulatory sexual selection, other post-copulatory traits or naturally selected traits. In addition, a sample of adult males from the same population in the wild revealed a positive correlation between investment in testes and weapons. Our study presents a critical contribution to a growing body of literature suggesting the allocation of resources to pre- and post-copulatory sexual traits is influenced by a resource allocation trade-off and that this trade-off may only be revealed with experimental manipulation.}, } @article {pmid29164291, year = {2018}, author = {Sayevand, HR and Bakhtiary, F and Pointner, A and Remely, M and Hippe, B and Hosseini, H and Haslberger, A}, title = {Bacterial Diversity in Traditional Doogh in Comparison to Industrial Doogh.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {386-393}, pmid = {29164291}, issn = {1432-0991}, mesh = {Biodiversity ; Cultured Milk Products/*microbiology ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Food Microbiology ; Iran ; Lactobacillus/classification/genetics/*isolation & purification/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Yogurt/*microbiology ; }, abstract = {Forty-four samples of traditional Doogh and yoghurt were collected from 13 regions of 4 provinces in west of Iran (13 area) and analyzed using molecular methods including PCR, denaturing gradient gel electrophoresis (DGGE) of 16S rDNA, and sequencing. Moreover, collected samples as well as samples from industrially Doogh were analyzed with quantitative real-time PCR (RT-PCR). Analyzed 16S rRNA gene sequences of Doogh samples could be allocated to the presence of Lactobacillus spp. The typical yoghurt starter culture bacteria included four different Lactobacillus species with possible probiotic properties, L. acidophilus, L. helveticus, L. kefiranofaciens, and L. amylovorus. DGGE of traditional Doogh and yoghurt and RT-PCR of traditional Doogh and yoghurt and also industrial Doogh samples demonstrated that traditional Doogh and yoghurt show a higher abundance of total bacteria and lactobacilli and a higher bacterial diversity, respectively. Considering diversity and higher probiotic bacteria content in traditional Doogh, consumers' healthiness in tribes and villages could be promoted with these indigenous products.}, } @article {pmid29162552, year = {2018}, author = {Padilla-García, N and Rojas-Andrés, BM and López-González, N and Castro, M and Castro, S and Loureiro, J and Albach, DC and Machon, N and Martínez-Ortega, MM}, title = {The challenge of species delimitation in the diploid-polyploid complex Veronica subsection Pentasepalae.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {196-209}, doi = {10.1016/j.ympev.2017.11.007}, pmid = {29162552}, issn = {1095-9513}, mesh = {Amplified Fragment Length Polymorphism Analysis ; Balkan Peninsula ; Base Sequence ; DNA, Plant/genetics ; *Diploidy ; Genome, Plant ; Geography ; Phylogeny ; *Polyploidy ; Principal Component Analysis ; Spain ; Species Specificity ; Veronica/*genetics ; }, abstract = {A reliable taxonomic framework and the identification of evolutionary lineages are essential for effective decisions in conservation biodiversity programs. However, phylogenetic reconstruction becomes extremely difficult when polyploidy and hybridization are involved. Veronica subsection Pentasepalae is a diploid-polyploid complex of ca. 20 species with ploidy levels ranging from 2x to 10x. Here, DNA-ploidy level estimations and AFLP fingerprinting were used to determine the evolutionary history, and species boundaries were reviewed in an integrated approach including also previous data (mainly morphology and sequence-based phylogenetic reconstructions). Molecular analyses were performed for 243 individuals from 95 populations, including for the first time all taxa currently recognized within the subsection. Phylogenetic reconstruction identified four main groups corresponding almost completely to the four clusters identified by genetic structure analyses. Multiple autopolyploidization events have occurred in the tetraploid V. satureiifolia giving rise to octoploid entities in central Europe and north of Spain, whereas hybridization is demonstrated to have occurred in several populations from the Balkan Peninsula. Furthermore, our study has established the taxonomic status of taxa, for the most part recovered as monophyletic. Cryptic taxa within the group have been identified, and a new species, Veronica dalmatica, is fully described. This study highlights the implications of polyploidy in species delimitation, and illustrates the importance to conserve polyploid populations as potential sources of diversification due to evolutionary significance of genome duplications in plant evolution.}, } @article {pmid29162551, year = {2018}, author = {Curto, M and Schachtler, C and Puppo, P and Meimberg, H}, title = {Using a new RAD-sequencing approach to study the evolution of Micromeria in the Canary islands.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {160-169}, doi = {10.1016/j.ympev.2017.11.005}, pmid = {29162551}, issn = {1095-9513}, mesh = {Base Sequence ; *Biological Evolution ; Ecosystem ; Geography ; *Islands ; Lamiaceae/*genetics ; Likelihood Functions ; Phylogeny ; Sequence Analysis, DNA/*methods ; Spain ; Species Specificity ; }, abstract = {As found in other oceanic islands, the Canary Islands include a large number of single island endemic species, some of which form clades that are broadly distributed within the archipelago. The genus Micromeria (Lamiaceae), for instance, includes groups of morphologically similar but ecologically diverse species on each island, representing a great model to investigate niche shifts and adaptation within the Canary Archipelago. Previous attempts to reconstruct phylogenetic relationships within the genus did not lead to robust phylogenies, presumably due to introgression and/or incomplete lineage sorting. In this study, we use a newly developed RAD-sequencing method to improve phylogenetic resolution and to better understand relationships among the Canary Island endemic Micromeria. Overall, we obtained 3571 loci that were genotyped for a total of 46 individuals of Micromeria. Our data reconstructed a highly resolved phylogeny, and corroborated the latest species reclassification of the M. varia s.l. species complex, the taxonomically most complicated group within the genus. Furthermore, taxa occupying similar ecological conditions in different islands, were shown to be closely related. This is the case of taxa from the laurel forest from La Gomera and Gran Canaria, suggesting that the laurel forest likely worked as a filter, only allowing the establishment of colonizers already pre-adapted to these conditions. We also found introgression between these species so it is also possible that the genes that facilitated the adaptation to laurel forest were swapped between Gran Canaria and La Gomera. The observations obtained in this study also allowed us to explain the role of introgression in the origin of M. varia s.l. species complex.}, } @article {pmid29162550, year = {2018}, author = {Weinell, JL and Brown, RM}, title = {Discovery of an old, archipelago-wide, endemic radiation of Philippine snakes.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {144-150}, doi = {10.1016/j.ympev.2017.11.004}, pmid = {29162550}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Biodiversity ; *Islands ; Philippines ; *Phylogeny ; Sequence Analysis, DNA ; Snakes/genetics/*physiology ; Time Factors ; }, abstract = {The extraordinarily rich land vertebrate biodiversity of the Philippines includes at least 112 species of terrestrial snakes (74% of which are endemic to the archipelago) in 41 genera (12% endemic). Endemic Philippine snake genera include Cyclocorus (two species), Hemibungarus (three species), Hologerrhum (two species), Oxyrhabdium (two species), and Myersophis (monotypic). Although Hemibungarus and Oxyrhabdium have been included in previous species-level phylogenies, the affinities of the other three Philippine endemic genera are completely unknown. We generated novel DNA sequences for six species from four genera and analyzed these in conjunction with data from earlier studies to infer a phylogeny for the group containing Colubridae, Elapoidea (Elapidae + Lamprophiidae), and Homalopsidae. We present a novel phylogenetic result that strongly supports the existence of an entirely endemic Philippine radiation of elapoid snakes that originated 35-25 million years ago. We provide a revised, phylogeny-based classification to accommodate the new clade, transfer Cyclocorus, Hologerrhum, and Myersophis to Lamprophiidae, and provide the first estimate of the evolutionary relationships among these genera and the related Oxyrhabdium, setting the stage for future investigation of this entirely endemic, novel Philippine elapoid radiation.}, } @article {pmid29162549, year = {2018}, author = {Slovák, M and Kučera, J and Lack, HW and Ziffer-Berger, J and Melicharková, A and Záveská, E and Vďačný, P}, title = {Diversification dynamics and transoceanic Eurasian-Australian disjunction in the genus Picris (Compositae) induced by the interplay of shifts in intrinsic/extrinsic traits and paleoclimatic oscillations.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {182-195}, doi = {10.1016/j.ympev.2017.11.006}, pmid = {29162549}, issn = {1095-9513}, mesh = {Africa, Northern ; Asia ; Asteraceae/*classification ; Australia ; Bayes Theorem ; *Biodiversity ; *Climate ; Models, Biological ; Phenotype ; Phylogeny ; Phylogeography ; Quantitative Trait, Heritable ; }, abstract = {Understanding transcontinental biogeographic patterns has been one of the main foci of the field of biogeography. While multiple explanations for transcontinental disjunctions have been proposed, little is still known about the relative importance of intrinsic and extrinsic traits for the diversification dynamics of disjunct taxa. Here, we study the evolutionary history of the genus Picris L. (Compositae), a great model for investigating the diversification dynamics of transoceanic bipolar disjunct organisms. Ancestral state reconstructions indicate that the most recent common ancestor (MRCA) of Picris was a semelparous and heterocarpic herb that lived in unpredictable environments of North Africa and West Asia. Diversification analyses suggest a significant shift in speciation ca. 1 million years ago, likely associated with the onset of the mid-Pleistocene revolution. Longevity characters are correlated with the evolution of particular fruit types and with environmental conditions. Heterocarpic species are mostly semelparous herbs strongly linked with unpredictable habitats, while homocarpic taxa are mostly iteroparous plants occurring in predictable environments. Binary-state speciation and extinction analyses suggest that homocarpy, iteroparity, and habitats predictability accelerate diversification. Although the combination of homocarpy and iteroparity evolved in several lineages, only members of the P. hieracioides group were able to colonise Eurasia and expand to Australia by transoceanic dispersal. Those findings indicate that large-scale colonisation events depend on a complex interplay of intrinsic and extrinsic factors.}, } @article {pmid29162404, year = {2018}, author = {Jacobson, J and Bush, S}, title = {Neglected Tropical Diseases, Neglected Communities, and Conflict: How Do We Leave No One Behind?.}, journal = {Trends in parasitology}, volume = {34}, number = {3}, pages = {175-177}, pmid = {29162404}, issn = {1471-5007}, mesh = {Armed Conflicts ; Disease Eradication/economics/*organization & administration/standards/trends ; Humans ; Neglected Diseases/economics/*prevention & control ; Preventive Health Services/economics/*organization & administration/*standards/trends ; *Residence Characteristics ; Tropical Climate ; }, abstract = {Most well established neglected tropical disease (NTD) programs have seen great progress towards disease control or elimination. Areas in conflict, however, are a looming challenge to reaching control and elimination targets. To be successful, programs and partners need to creatively adapt to local circumstances and embrace new colleagues not traditionally seen as NTD implementers.}, } @article {pmid29162391, year = {2018}, author = {Richard, J and Prévost, J and Alsahafi, N and Ding, S and Finzi, A}, title = {Impact of HIV-1 Envelope Conformation on ADCC Responses.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {253-265}, doi = {10.1016/j.tim.2017.10.007}, pmid = {29162391}, issn = {1878-4380}, support = {352417//CIHR/Canada ; }, abstract = {HIV-1 envelope glycoproteins (Env) represent the only virus-specific antigen exposed at the surface of infected cells. In its unliganded form, Env from primary viruses samples a 'closed' conformation (State 1), which is preferentially recognized by broadly neutralizing antibodies (bNAbs). CD4 engagement drives Env into an intermediate 'partially open' (State 2) and then into the 'open' CD4-bound conformation (State 3). Emerging evidence suggests a link between Env conformation and Ab-dependent cellular cytotoxicity (ADCC). HIV-1-infected cells exposing Env in the CD4-bound conformation are susceptible to ADCC mediated by CD4-induced Abs and HIV+sera. Cells exposing State 1 Env are susceptible to ADCC mediated by bNAbs. Here, we discuss how Env conformation affects ADCC responses and in vitro measurements.}, } @article {pmid29161615, year = {2018}, author = {Mignolet, J and Panis, G and Viollier, PH}, title = {More than a Tad: spatiotemporal control of Caulobacter pili.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {79-86}, doi = {10.1016/j.mib.2017.10.017}, pmid = {29161615}, issn = {1879-0364}, mesh = {Bacterial Adhesion/genetics/physiology ; Bacterial Proteins/metabolism ; Caulobacter/*genetics/metabolism ; Fimbriae, Bacterial/*genetics/physiology ; Gene Expression Regulation, Bacterial ; Models, Molecular ; Pseudomonas aeruginosa/genetics ; }, abstract = {The Type IV pilus (T4P) is a powerful and sophisticated bacterial nanomachine involved in numerous cellular processes, including adhesion, DNA uptake and motility. Aside from the well-described subtype T4aP of the Gram-negative genera, including Myxococcus, Pseudomonas and Neisseria, the Tad (tight adherence) pilus secretion system re-shuffles homologous parts from other secretion systems along with uncharacterized components into a new type of protein translocation apparatus. A representative of the Tad apparatus, the Caulobacter crescentus pilus assembly (Cpa) machine is built exclusively at the newborn cell pole once per cell cycle. Recent comprehensive genetic analyses unearthed a myriad of spatiotemporal determinants acting on the Tad/Cpa system, many of which are conserved in other α-proteobacteria, including obligate intracellular pathogens and symbionts.}, } @article {pmid29161442, year = {2018}, author = {Tamarit, D and Neuvonen, MM and Engel, P and Guy, L and Andersson, SGE}, title = {Origin and Evolution of the Bartonella Gene Transfer Agent.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {451-464}, doi = {10.1093/molbev/msx299}, pmid = {29161442}, issn = {1537-1719}, abstract = {Gene transfer agents (GTAs) are domesticated bacteriophages that have evolved into molecular machines for the transfer of bacterial DNA. Despite their widespread nature and their biological implications, the mechanisms and selective forces that drive the emergence of GTAs are still poorly understood. Two GTAs have been identified in the Alphaproteobacteria: the RcGTA, which is widely distributed in a broad range of species; and the BaGTA, which has a restricted host range that includes vector-borne intracellular bacteria of the genus Bartonella. The RcGTA packages chromosomal DNA randomly, whereas the BaGTA particles contain a relatively higher fraction of genes for host interaction factors that are amplified from a nearby phage-derived origin of replication. In this study, we compare the BaGTA genes with homologous bacteriophage genes identified in the genomes of Bartonella species and close relatives. Unlike the BaGTA, the prophage genes are neither present in all species, nor inserted into homologous genomic sites. Phylogenetic inferences and substitution frequency analyses confirm codivergence of the BaGTA with the host genome, as opposed to multiple integration and recombination events in the prophages. Furthermore, the organization of segments flanking the BaGTA differs from that of the prophages by a few rearrangement events, which have abolished the normal coordination between phage genome replication and phage gene expression. Based on the results of our comparative analysis, we propose a model for how a prophage may be transformed into a GTA that transfers amplified bacterial DNA segments.}, } @article {pmid29161408, year = {2018}, author = {Waters, SA and Livernois, AM and Patel, H and O'Meally, D and Craig, JM and Marshall Graves, JA and Suter, CM and Waters, PD}, title = {Landscape of DNA Methylation on the Marsupial X.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {431-439}, doi = {10.1093/molbev/msx297}, pmid = {29161408}, issn = {1537-1719}, abstract = {DNA methylation plays a key role in maintaining transcriptional silence on the inactive X chromosome of eutherian mammals. Beyond eutherians, there are limited genome wide data on DNA methylation from other vertebrates. Previous studies of X borne genes in various marsupial models revealed no differential DNA methylation of promoters between the sexes, leading to the conclusion that CpG methylation plays no role in marsupial X-inactivation. Using reduced representation bisulfite sequencing, we generated male and female CpG methylation profiles in four representative vertebrates (mouse, gray short-tailed opossum, platypus, and chicken). A variety of DNA methylation patterns were observed. Platypus and chicken displayed no large-scale differential DNA methylation between the sexes on the autosomes or the sex chromosomes. As expected, a metagene analysis revealed hypermethylation at transcription start sites (TSS) of genes subject to X-inactivation in female mice. This contrasted with the opossum, in which metagene analysis did not detect differential DNA methylation between the sexes at TSSs of genes subject to X-inactivation. However, regions flanking TSSs of these genes were hypomethylated. Our data are the first to demonstrate that, for genes subject to X-inactivation in both eutherian and marsupial mammals, there is a consistent difference between DNA methylation levels at TSSs and immediate flanking regions, which we propose has a silencing effect in both groups.}, } @article {pmid29161377, year = {2018}, author = {Ravi, A and Valdés-Varela, L and Gueimonde, M and Rudi, K}, title = {Transmission and persistence of IncF conjugative plasmids in the gut microbiota of full-term infants.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix158}, pmid = {29161377}, issn = {1574-6941}, abstract = {Conjugative plasmids represent major reservoirs for horizontal transmission of antibiotic resistance and virulence genes. Our knowledge about the ecology and persistence of these plasmids in the gut microbiota remains limited. The IncF plasmids are the most widespread in clinical samples and in healthy humans and the main aim of this work was to study their ecology and association with the developing gut microbiota. Using a longitudinal (2, 10, 30 and 90 days) cohort of full-term infants, we investigated the transmission and persistence of IncFIA and IncFIB plasmids. The prevalence of IncFIB plasmids was higher than IncFIA in the cohort, while IncFIA always co-occurred with IncFIB. However, the relative gene abundance of IncFIA was significantly higher than IncFIB for all time points, indicating that IncFIA may be a higher copy-number plasmid. Through linear discriminant analysis effect size and operational taxonomic unit-level associations, we observed major differences in the abundance of Enterobacteriaceae in samples positive and negative for IncFIB. This association was significant at 2, 10 and 30 days and showed an association with vaginal delivery. From shot-gun analyses, we assembled de novo multi-replicon shared (IncFIA/IncFIB) and integrated (IncFIA/IB) plasmids that were persistent through the dataset. Overall, the study demonstrates the nature of IncF plasmids in complex microbial communities.}, } @article {pmid29160913, year = {2018}, author = {Vellnow, N and Marie-Orleach, L and Zadesenets, KS and Schärer, L}, title = {Bigger testes increase paternity in a simultaneous hermaphrodite, independently of the sperm competition level.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {180-196}, doi = {10.1111/jeb.13212}, pmid = {29160913}, issn = {1420-9101}, abstract = {Hermaphroditic animals face the fundamental evolutionary optimization problem of allocating their resources to their male vs. female reproductive function (e.g. testes and sperm vs. ovaries and eggs), and this optimal sex allocation can be affected by both pre- and post-copulatory sexual selection. For example, local sperm competition (LSC) - the competition between related sperm for the fertilization of a partner's ova - occurs in small mating groups and can favour a female-biased sex allocation, because, under LSC, investment into sperm production is predicted to show diminishing fitness returns. Here, we test whether higher testis investment increases an individual's paternity success under sperm competition, and whether the strength of this effect diminishes when LSC is stronger, as predicted by sex allocation theory. We created two subsets of individuals of the simultaneously hermaphroditic flatworm Macrostomum lignano - by sampling worms from either the highest or lowest quartile of the testis investment distribution - and estimated their paternity success in group sizes of either three (strong LSC) or eight individuals (weak LSC). Specifically, using transgenic focal individuals expressing a dominant green-fluorescent protein marker, we showed that worms with high testis investment sired 22% more offspring relative to those with low investment, corroborating previous findings in M. lignano and other species. However, the strength of this effect was not significantly modulated by the experienced group size, contrasting theoretical expectations of more strongly diminishing fitness returns under strong LSC. We discuss the possible implications for the evolutionary maintenance of hermaphroditism in M. lignano.}, } @article {pmid29160556, year = {2018}, author = {Liedtke, HC}, title = {Digest: Room for geckos of all shapes and sizes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {213-214}, doi = {10.1111/evo.13401}, pmid = {29160556}, issn = {1558-5646}, } @article {pmid29160554, year = {2018}, author = {Samani, P}, title = {Digest: Evolution of sperm size and number in external fertilizers.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {211-212}, doi = {10.1111/evo.13400}, pmid = {29160554}, issn = {1558-5646}, } @article {pmid29160553, year = {2018}, author = {Rautiala, P and Helanterä, H and Puurtinen, M}, title = {The evolutionary dynamics of adaptive virginity, sex-allocation, and altruistic helping in haplodiploid animals.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {30-38}, doi = {10.1111/evo.13399}, pmid = {29160553}, issn = {1558-5646}, abstract = {In haplodiploids, females can produce sons from unfertilized eggs without mating. However, virgin reproduction is usually considered to be a result of a failure to mate, rather than an adaptation. Here, we build an analytical model for evolution of virgin reproduction, sex-allocation, and altruistic female helping in haplodiploid taxa. We show that when mating is costly (e.g., when mating increases predation risk), virginity can evolve as an adaptive female reproductive strategy. Furthermore, adaptive virginity results in strongly divergent sex-ratios in mated and virgin queen nests ("split sex ratios"), which promotes the evolution of altruistic helping by daughters in mated queen nests. However, when helpers evolve to be efficient and increase nest production significantly, virgin reproduction is selected against. Our results suggest that adaptive virginity could have been an important stepping stone on the pathway to eusociality in haplodiploids. We further show that virginity can be an adaptive reproductive strategy also in primitively social haplodiploids if workers bias the sex ratio toward females. By remaining virgin, queens are free to produce sons, the more valuable sex in a female-biased population. Our work brings a new dimension to the studies linking reproductive strategies with social evolution.}, } @article {pmid29160310, year = {2018}, author = {Zhang, J and Bu, X and Wang, H and Zhu, Y and Geng, Y and Nihira, NT and Tan, Y and Ci, Y and Wu, F and Dai, X and Guo, J and Huang, YH and Fan, C and Ren, S and Sun, Y and Freeman, GJ and Sicinski, P and Wei, W}, title = {Cyclin D-CDK4 kinase destabilizes PD-L1 via cullin 3-SPOP to control cancer immune surveillance.}, journal = {Nature}, volume = {553}, number = {7686}, pages = {91-95}, pmid = {29160310}, issn = {1476-4687}, support = {R01 CA083688/CA/NCI NIH HHS/United States ; R01 CA200651/CA/NCI NIH HHS/United States ; P01 CA080111/CA/NCI NIH HHS/United States ; P50 CA101942/CA/NCI NIH HHS/United States ; R01 GM094777/GM/NIGMS NIH HHS/United States ; R01 CA200573/CA/NCI NIH HHS/United States ; R01 CA202634/CA/NCI NIH HHS/United States ; K99 CA212292/CA/NCI NIH HHS/United States ; R01 CA177910/CA/NCI NIH HHS/United States ; R01 GM089763/GM/NIGMS NIH HHS/United States ; R01 CA132740/CA/NCI NIH HHS/United States ; R01 CA229307/CA/NCI NIH HHS/United States ; R01 CA190509/CA/NCI NIH HHS/United States ; }, mesh = {14-3-3 Proteins/metabolism ; Animals ; B7-H1 Antigen/biosynthesis/*metabolism ; Cdh1 Proteins/metabolism ; Cell Cycle ; Cell Line ; Cullin Proteins/*metabolism ; Cyclin D/*metabolism ; Cyclin-Dependent Kinase 4/antagonists & inhibitors/*metabolism ; Cyclin-Dependent Kinase 6/antagonists & inhibitors ; Female ; Humans ; *Immunologic Surveillance ; Lymphocytes, Tumor-Infiltrating/cytology/immunology ; Male ; Mice ; Neoplasms/*immunology ; Nuclear Proteins/chemistry/*metabolism ; Phosphorylation ; Programmed Cell Death 1 Receptor/metabolism ; Prostatic Neoplasms/immunology ; Proteasome Endopeptidase Complex/metabolism ; Protein Stability ; Proteolysis ; Repressor Proteins/chemistry/*metabolism ; Tumor Escape/*immunology ; }, abstract = {Treatments that target immune checkpoints, such as the one mediated by programmed cell death protein 1 (PD-1) and its ligand PD-L1, have been approved for treating human cancers with durable clinical benefit. However, many patients with cancer fail to respond to compounds that target the PD-1 and PD-L1 interaction, and the underlying mechanism(s) is not well understood. Recent studies revealed that response to PD-1-PD-L1 blockade might correlate with PD-L1 expression levels in tumour cells. Hence, it is important to understand the mechanistic pathways that control PD-L1 protein expression and stability, which can offer a molecular basis to improve the clinical response rate and efficacy of PD-1-PD-L1 blockade in patients with cancer. Here we show that PD-L1 protein abundance is regulated by cyclin D-CDK4 and the cullin 3-SPOP E3 ligase via proteasome-mediated degradation. Inhibition of CDK4 and CDK6 (hereafter CDK4/6) in vivo increases PD-L1 protein levels by impeding cyclin D-CDK4-mediated phosphorylation of speckle-type POZ protein (SPOP) and thereby promoting SPOP degradation by the anaphase-promoting complex activator FZR1. Loss-of-function mutations in SPOP compromise ubiquitination-mediated PD-L1 degradation, leading to increased PD-L1 levels and reduced numbers of tumour-infiltrating lymphocytes in mouse tumours and in primary human prostate cancer specimens. Notably, combining CDK4/6 inhibitor treatment with anti-PD-1 immunotherapy enhances tumour regression and markedly improves overall survival rates in mouse tumour models. Our study uncovers a novel molecular mechanism for regulating PD-L1 protein stability by a cell cycle kinase and reveals the potential for using combination treatment with CDK4/6 inhibitors and PD-1-PD-L1 immune checkpoint blockade to enhance therapeutic efficacy for human cancers.}, } @article {pmid29160202, year = {2018}, author = {Li, X and Tambong, J and Yuan, KX and Chen, W and Xu, H and Lévesque, CA and De Boer, SH}, title = {Re-classification of Clavibacter michiganensis subspecies on the basis of whole-genome and multi-locus sequence analyses.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {234-240}, pmid = {29160202}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genome, Bacterial ; Micrococcaceae/*classification ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Although the genus Clavibacter was originally proposed to accommodate all phytopathogenic coryneform bacteria containing B2γ diaminobutyrate in the peptidoglycan, reclassification of all but one species into other genera has resulted in the current monospecific status of the genus. The single species in the genus, Clavibacter michiganensis, has multiple subspecies, which are all highly host-specific plant pathogens. Whole genome analysis based on average nucleotide identity and digital DNA-DNA hybridization as well as multi-locus sequence analysis (MLSA) of seven housekeeping genes support raising each of the C. michiganensis subspecies to species status. On the basis of whole genome and MLSA data, we propose the establishment of two new species and three new combinations: Clavibacter capsici sp. nov., comb. nov. and Clavibacter tessellarius sp. nov., comb. nov., and Clavibacter insidiosus comb. nov., Clavibacter nebraskensis comb. nov. and Clavibacter sepedonicus comb. nov.}, } @article {pmid29160201, year = {2018}, author = {Feng, T and Kim, KH and Jeong, SE and Kim, W and Jeon, CO}, title = {Aquicoccus porphyridii gen. nov., sp. nov., isolated from a small marine red alga, Porphyridium marinum.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {283-288}, doi = {10.1099/ijsem.0.002498}, pmid = {29160201}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Porphyridium/*microbiology ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, non-motile and aerobic bacterial strain, designated L1 8-17T, was isolated from a marine alga, Porphyridium marinum, in South Korea. Cells of strain L1 8-17T were found to be oxidase- and catalase-positive cocci without flagella. Growth of strain L1 8-17T was observed at 20-40 °C (optimum, 37 °C), pH 6.0-10.0 (optimum, pH 7.0-8.0) and in the presence of 0-7 % (w/v) NaCl (optimum, 2-3 %). The isoprenoid quinone detected was only ubiquinone-10. Summed feature 8 (comprising C18 : 1ω7c/C18 : 1ω6c) and C16 : 0 were detected as major cellular fatty acids. The major polar lipids of strain L1 8-17T consisted of phosphatidylcholine, phosphatidylglycerol, phosphatidylethanolamine, an unidentified aminolipid, an unidentified phospholipid and an unidentified lipid. The G+C content of the genomic DNA was 59.3 mol%. Strain L1 8-17T was most closely related to Marimonas arenosa CAU 1311T, Tropicibacter naphthalenivorans C02T and Donghicola eburneus SW-277T with 96.68, 96.68 and 96.60 % 16S rRNA gene sequence similarities, respectively, but the strain formed a phylogenetic lineage clearly distinct from them within the family Rhodobacteraceae. On the basis of phenotypic, chemotaxonomic and molecular properties, strain L1 8-17T represents a novel genus of the family Rhodobacteraceae, for which the name Aquicoccus porphyridii gen. nov., sp. nov. is proposed. The type strain of the type species is L1 8-17T (KACC 18806T=JCM 31543T).}, } @article {pmid29160200, year = {2018}, author = {Lee, Y and Jeon, CO}, title = {Methylobacterium frigidaeris sp. nov., isolated from an air conditioning system.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {299-304}, doi = {10.1099/ijsem.0.002500}, pmid = {29160200}, issn = {1466-5034}, mesh = {*Air Conditioning ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Methylobacterium/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A reddish pink-pigmented, Gram-stain-negative, aerobic and methylotrophic bacterial strain, designated strain IER25-16T, was isolated from a laboratory air conditioning system in the Republic of Korea. Cells were motile rods showing catalase- and oxidase-positive reactions. Strain IER25-16T grew at 10-40 °C (optimum, 30 °C), at pH 4.0-7.0 (optimum, pH 5.0-7.0) and in the presence of 0-1.0 % (w/v) NaCl (optimum, 0 %). The major respiratory quinone was ubiquinone-10 and ubiquinone-9 was also detected as the minor respiratory quinone. Summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c) was detected as the predominant fatty acids. The genomic DNA G+C content of strain IER25-16T was 70.0 mol%. Phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that strain IER25-16T belonged to the genus Methylobacterium of the class Alphaproteobacteria. Strain IER25-16T was most closely related to Methylobacterium platani PMB02T (97.9 %), Methylobacterium aquaticum GR16T (97.9 %) and Methylobacterium tarhaniae N4211T (97.5 %). The average nucleotide identity and in silico DNA-DNA hybridization values between strain IER25-16T and M. platani, M. aquaticum and M. tarhaniae were 88.3, 88.8 and 89.6 % and 36.2, 37.3 and 39.3 %, respectively. The phenotypic and chemotaxonomic features and the phylogenetic inference clearly suggested that strain IER25-16T represents a novel species of the genus Methylobacterium, for which the name Methylobacteriumfrigidaeris sp. nov. is proposed. The type strain is strain IER25-16T (=KACC 19280T=JCM 32048T).}, } @article {pmid29160198, year = {2018}, author = {Niemhom, N and Thawai, C}, title = {Herbidospora soli sp. nov., isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {294-298}, doi = {10.1099/ijsem.0.002503}, pmid = {29160198}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Thailand ; Ubiquinone/chemistry ; }, abstract = {A novel actinomycete strain PS42-9T, which formed short chains of spores borne on the tip of long sporophores arising from the substrate mycelium, was isolated from soil in Phu-Sang National Park, Phayao province, Thailand. The isolate contained meso-diaminopimelic acid in the cell-wall peptidoglycan. The whole-cell sugars of strain PS42-9T were glucose, madurose, mannose, rhamnose and ribose. The characteristic phospholipids were phosphatidylethanolamine, phosphatidylmethylethanolamine, hydroxyphosphatidylethanolamine and ninhydrin-positive glycophospholipids. The major menaquinone was MK-10(H4). The main cellular fatty acids were C17 : 1ω8c and C17 : 0. The G+C content of the genomic DNA was 71.5 mol%. Phylogenetic analysis using 16S rRNA gene sequences revealed that strain PS42-9T should be classified in the genus Herbidospora and was closely related to Herbidospora sakaeratensis DMKUA 205T (99.10 %) and Herbidospora yilanensis NBRC 106371T (98.61 %). The result of DNA-DNA hybridization and some physiological and biochemical properties indicated that strain PS42-9T could be readily distinguished from its closest phylogenetic relatives. On the basis of these phenotypic and genotypic data, this strain represents a novel species, for which the name Herbidospora soli sp. nov. is proposed. The type strain is PS42-9T (=BCC 46909T=NBRC 108780T).}, } @article {pmid29160196, year = {2018}, author = {Wang, Q and Sun, YW and Liu, J and Zhang, DC}, title = {Rheinheimera marina sp. nov., isolated from a deep-sea seamount.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {266-270}, doi = {10.1099/ijsem.0.002496}, pmid = {29160196}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chromatiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Pacific Ocean ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {A bacterial strain designated TP462T, isolated from a seamount near the Yap Trench in the tropical western Pacific, was characterized using a polyphasic taxonomic approach. Strain TP462T was found to be Gram-stain-negative, aerobic, rod-shaped and motile by means of a single polar flagellum. Growth occurred at 4-37 °C (optimum, 25-30 °C) and with 0-4.0 % NaCl (optimum, 2-3 %). Phylogenetic analysis based on 16S rRNA gene sequence showed that strain TP462T was related to the genus Rheinheimera and had the highest 16S rRNA gene sequence similarity with the type strain Rheinheimera tangshanensis JA3-B52T (96.8 %). The predominant cellular fatty acids were C17 : 1ω8c, summed feature 3 (composed of iso-C15 : 0 2-OH and/or C16 : 1ω7c) and C16 : 0. The polar lipid profile contained phosphatidylglycerol, phosphatidylethanolamine and two unidentified lipids. The genomic DNA G+C content of strain TP462T was 48.7 mol%. On the basis of the evidence presented in this study, strain TP462T represents a novel species of the genus Rheinheimera, for which we propose the name Rheinheimera marina sp. nov. (type strain TP462T=KACC 18560T=CGMCC 1.15399T).}, } @article {pmid29160034, year = {2018}, author = {Suter, EA and Pachiadaki, M and Taylor, GT and Astor, Y and Edgcomb, VP}, title = {Free-living chemoautotrophic and particle-attached heterotrophic prokaryotes dominate microbial assemblages along a pelagic redox gradient.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {693-712}, doi = {10.1111/1462-2920.13997}, pmid = {29160034}, issn = {1462-2920}, abstract = {Using the anoxic Cariaco Basin as a natural laboratory, particle association of bacterial and archaeal taxa was assessed by iTag sequencing and qPCR gene assays of samples spanning an oxic-anoxic-euxinic gradient. A total of 10%-12% of all bacterial and archaeal cells were found in the particle-associated (PA) fraction, operationally defined as prokaryotes captured on 2.7 µm membranes. Both redox condition and size fraction segregated bacterial taxa. Archaeal taxa varied according to redox conditions, but were similar between size fractions. Taxa putatively associated with chemoautotrophic sulfur oxidation and nitrification dominated the free-living (FL) fraction throughout the oxycline (< 1-120 µM O2) and upper anoxic layer. Bacteria in the oxycline's PA fraction included taxa known to be aerobic and anaerobic chemoorganotrophs. At shallow anoxic depths, PA taxa were primarily affiliated with anaerobic sulfate (SO42-)-reducing lineages. PA fractions in the most sulfidic samples were dominated by taxa affiliated with CH4 oxidizing, fermenting and SO42- reducing lineages. Prevalence of particle-associated SO42--reducing taxa and abundant sulfur-oxidizing taxa in both size fractions across the oxic-anoxic interface is consistent with the cryptic sulfur cycling concept. Bacterial assemblage diversity in the PA fraction always exceeded the FL fraction except in the most oxic samples, whereas Archaeal diversity was not consistently different between size fractions. Our results suggest that these particle-associated and free-living bacterial assemblages are functionally different and that the interplay between particle microhabitats and surrounding geochemical regimes is a strong selective force shaping microbial communities throughout the water column.}, } @article {pmid29160027, year = {2018}, author = {Liu, P and Pommerenke, B and Conrad, R}, title = {Identification of Syntrophobacteraceae as major acetate-degrading sulfate reducing bacteria in Italian paddy soil.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {337-354}, doi = {10.1111/1462-2920.14001}, pmid = {29160027}, issn = {1462-2920}, abstract = {Methane is an important greenhouse gas and acetate is the most important intermediate (average 70%) of the carbon flow to CH4 in paddy fields. Sulfate (e.g., gypsum) application can reduce CH4 emissions up to 70%. However, the effect of gypsum application on acetate degradation and the microbial communities involved are unclear. Therefore, we studied acetate-dependent sulfate reduction in anoxic microcosms of Italian rice paddy soil, combining profiling of 16S rRNA and dissimilatory sulfite reductase (dsrB) genes and transcripts and rRNA based stable isotope probing (SIP) analysis. Methane production was completely inhibited by gypsum in the absence of exogenous acetate. Amended acetate (either 13 C labelled or non-labelled) was stoichiometrically coupled to sulfate reduction or CH4 production. With methyl fluoride in the presence of sulfate, added propionate and butyrate were incompletely oxidized to acetate, which transiently accumulated. After the depletion of propionate and butyrate the accumulated acetate was rapidly consumed. The relative abundance of dsrB and 16S rRNA genes and transcripts from Syntrophobacteraceae (Desulfovirga spp., Syntrophobacter spp. and unclassified Syntrophobacteraceae) increased upon addition of gypsum and acetate. Simultaneously, Syntrophobacteraceae affiliated species were significantly labelled with 13 C. In addition, minor groups like Desulforhabdus spp., Desulfobacca spp. and Desulfotomaculum spp. substantially incorporated 13 C into their nucleic acids. The relative abundance of Desulfovibrio spp. slightly increased upon gypsum amendments. However, 13 C labelling of Desulfovibrio spp. was only moderate. In summary, Syntrophobacteraceae affiliated species were identified as the major acetotrophic sulfate reducers (SRB) in Italian paddy soil. The identification of these SRB as dominant acetate degraders well explained the scenarios of competition between SRB and acetoclastic methanogens as observed in rice paddy soil.}, } @article {pmid29160024, year = {2018}, author = {Bertuol-Garcia, D and Morsello, C and N El-Hani, C and Pardini, R}, title = {A conceptual framework for understanding the perspectives on the causes of the science-practice gap in ecology and conservation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1032-1055}, doi = {10.1111/brv.12385}, pmid = {29160024}, issn = {1469-185X}, abstract = {Applying scientific knowledge to confront societal challenges is a difficult task, an issue known as the science-practice gap. In Ecology and Conservation, scientific evidence has been seldom used directly to support decision-making, despite calls for an increasing role of ecological science in developing solutions for a sustainable future. To date, multiple causes of the science-practice gap and diverse approaches to link science and practice in Ecology and Conservation have been proposed. To foster a transparent debate and broaden our understanding of the difficulties of using scientific knowledge, we reviewed the perceived causes of the science-practice gap, aiming to: (i) identify the perspectives of ecologists and conservation scientists on this problem, (ii) evaluate the predominance of these perspectives over time and across journals, and (iii) assess them in light of disciplines studying the role of science in decision-making. We based our review on 1563 sentences describing causes of the science-practice gap extracted from 122 articles and on discussions with eight scientists on how to classify these sentences. The resulting process-based framework describes three distinct perspectives on the relevant processes, knowledge and actors in the science-practice interface. The most common perspective assumes only scientific knowledge should support practice, perceiving a one-way knowledge flow from science to practice and recognizing flaws in knowledge generation, communication, and/or use. The second assumes that both scientists and decision-makers should contribute to support practice, perceiving a two-way knowledge flow between science and practice through joint knowledge-production/integration processes, which, for several reasons, are perceived to occur infrequently. The last perspective was very rare, and assumes scientists should put their results into practice, but they rarely do. Some causes (e.g. cultural differences between scientists and decision-makers) are shared with other disciplines, while others seem specific to Ecology and Conservation (e.g. inadequate research scales). All identified causes require one of three general types of solutions, depending on whether the causal factor can (e.g. inadequate research questions) or cannot (e.g. scientific uncertainty) be changed, or if misconceptions (e.g. undervaluing abstract knowledge) should be solved. The unchanged predominance of the one-way perspective over time may be associated with the prestige of evidence-based conservation and suggests that debates in Ecology and Conservation lag behind trends in other disciplines towards bidirectional views ascribing larger roles to decision-makers. In turn, the two-way perspective seems primarily restricted to research traditions historically isolated from mainstream conservation biology. All perspectives represented superficial views of decision-making by not accounting for limits to human rationality, complexity of decision-making contexts, fuzzy science-practice boundaries, ambiguity brought about by science, and different types of knowledge use. However, joint knowledge-production processes from the two-way perspective can potentially allow for democratic decision-making processes, explicit discussions of values and multiple types of science use. To broaden our understanding of the interface and foster productive science-practice linkages, we argue for dialogue among different research traditions within Ecology and Conservation, joint knowledge-production processes between scientists and decision-makers and interdisciplinarity across Ecology, Conservation and Political Science in both research and education.}, } @article {pmid29160003, year = {2018}, author = {Mercier, C and Lossouarn, J and Nesbø, CL and Haverkamp, THA and Baudoux, AC and Jebbar, M and Bienvenu, N and Thiroux, S and Dupont, S and Geslin, C}, title = {Two viruses, MCV1 and MCV2, which infect Marinitoga bacteria isolated from deep-sea hydrothermal vents: functional and genomic analysis.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {577-587}, doi = {10.1111/1462-2920.13967}, pmid = {29160003}, issn = {1462-2920}, abstract = {Viruses represent a driving force in the evolution of microorganisms including those thriving in extreme environments. However, our knowledge of the viral diversity associated to microorganisms inhabiting the deep-sea hydrothermal vents remains limited. The phylum of Thermotogae, including thermophilic bacteria, is well represented in this environment. Only one virus was described in this phylum, MPV1 carried by Marinitoga piezophila. In this study, we report on the functional and genomic characterization of two new bacterioviruses that infect bacteria from the Marinitoga genus. Marinitoga camini virus 1 and 2 (MCV1 and MCV2) are temperate siphoviruses with a linear dsDNA genome of 53.4 kb and 50.5 kb respectively. Here, we present a comparative genomic analysis of the MCV1 and MCV2 viral genomes with that of MPV1. The results indicate that even if the host strains come from geographically distant sites, their genomes share numerous similarities. Interestingly, heavy metals did not induce viral production, instead the host of MCV1 produced membrane vesicles. This study highlights interaction of mobile genetic elements (MGE) with their hosts and the importance of including hosts-MGEs' relationships in ecological studies.}, } @article {pmid29159997, year = {2018}, author = {Mukhopadhya, I and Moraïs, S and Laverde-Gomez, J and Sheridan, PO and Walker, AW and Kelly, W and Klieve, AV and Ouwerkerk, D and Duncan, SH and Louis, P and Koropatkin, N and Cockburn, D and Kibler, R and Cooper, PJ and Sandoval, C and Crost, E and Juge, N and Bayer, EA and Flint, HJ}, title = {Sporulation capability and amylosome conservation among diverse human colonic and rumen isolates of the keystone starch-degrader Ruminococcus bromii.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {324-336}, pmid = {29159997}, issn = {1462-2920}, support = {//Wellcome Trust/United Kingdom ; }, abstract = {Ruminococcus bromii is a dominant member of the human colonic microbiota that plays a 'keystone' role in degrading dietary resistant starch. Recent evidence from one strain has uncovered a unique cell surface 'amylosome' complex that organizes starch-degrading enzymes. New genome analysis presented here reveals further features of this complex and shows remarkable conservation of amylosome components between human colonic strains from three different continents and a R. bromii strain from the rumen of Australian cattle. These R. bromii strains encode a narrow spectrum of carbohydrate active enzymes (CAZymes) that reflect extreme specialization in starch utilization. Starch hydrolysis products are taken up mainly as oligosaccharides, with only one strain able to grow on glucose. The human strains, but not the rumen strain, also possess transporters that allow growth on galactose and fructose. R. bromii strains possess a full complement of sporulation and spore germination genes and we demonstrate the ability to form spores that survive exposure to air. Spore formation is likely to be a critical factor in the ecology of this nutritionally highly specialized bacterium, which was previously regarded as 'non-sporing', helping to explain its widespread occurrence in the gut microbiota through the ability to transmit between hosts.}, } @article {pmid29159995, year = {2018}, author = {Nieves-Morión, M and Flores, E}, title = {Multiple ABC glucoside transporters mediate sugar-stimulated growth in the heterocyst-forming cyanobacterium Anabaena sp. strain PCC 7120.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {40-48}, doi = {10.1111/1758-2229.12603}, pmid = {29159995}, issn = {1758-2229}, abstract = {Cyanobacteria are generally capable of photoautotrophic growth and are widely distributed on Earth. The model filamentous, heterocyst-forming strain Anabaena sp. PCC 7120 has long been considered as a strict photoautotroph but is now known to be able to assimilate fructose. We have previously described two components of ABC glucoside uptake transporters from Anabaena that are involved in uptake of the sucrose analog esculin: GlsC [a nucleotide-binding domain subunit (NBD)] and GlsP [a transmembrane component (TMD)]. Here, we created Anabaena mutants of genes encoding three further ABC transporter components needed for esculin uptake: GlsD (NBD), GlsQ (TMD) and GlsR (periplasmic substrate-binding protein). Phototrophic growth of Anabaena was significantly stimulated by sucrose, fructose and glucose. Whereas the glsC and glsD mutants were drastically hampered in sucrose-stimulated growth, the different gls mutants were generally impaired in sugar-dependent growth. Our results suggest the participation of Gls and other ABC transporters encoded in the Anabaena genome in sugar-stimulated growth. Additionally, Gls transporter components influence the function of septal junctions in the Anabaena filament. We suggest that mixotrophic growth is important in cyanobacterial physiology and may be relevant for the wide success of these organisms in diverse environments.}, } @article {pmid29159973, year = {2018}, author = {Chen, Y and Li, B and Cen, K and Lu, Y and Zhang, S and Wang, C}, title = {Diverse effect of phosphatidylcholine biosynthetic genes on phospholipid homeostasis, cell autophagy and fungal developments in Metarhizium robertsii.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {293-304}, doi = {10.1111/1462-2920.13998}, pmid = {29159973}, issn = {1462-2920}, abstract = {Phosphatidylcholine (PC) plays an important role in maintaining membrane integrity and functionality. In this study, two key genes (Mrpct and Mrpem) putatively involved in the cytidine diphosphate (CDP)-choline and phosphatidylethanolamine N-methyltransferase (PEMT) pathways for PC biosynthesis were characterized in the insect pathogenic fungus Metarhizium robertsii. The results indicated that disruption of Mrpct did not lead to any reduction of total PC content but impaired fungal virulence and increased cellular accumulation of triacylglycerol. Deletion of Mrpem reduced PC content and impaired fungal conidiation and infection structure differentiation but did not result in virulence defects. Lipidomic analysis revealed that deletion of Mrpct and Mrpem resulted in dissimilar effects on increase and decrease of PC moieties and other phospholipid species accumulations. Interestingly, we found that these two genes played opposite roles in activation of cell autophagy when the fungi were grown in a nutrient-rich medium. The connection between PC metabolism and autophagy was confirmed because PC content was drastically reduced in Mratg8Δ and that the addition of PC could rescue null mutant sporulation defect. The results of this study facilitate the understanding of PC metabolism on fungal physiology.}, } @article {pmid29159966, year = {2018}, author = {Pasulka, AL and Thamatrakoln, K and Kopf, SH and Guan, Y and Poulos, B and Moradian, A and Sweredoski, MJ and Hess, S and Sullivan, MB and Bidle, KD and Orphan, VJ}, title = {Interrogating marine virus-host interactions and elemental transfer with BONCAT and nanoSIMS-based methods.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {671-692}, doi = {10.1111/1462-2920.13996}, pmid = {29159966}, issn = {1462-2920}, abstract = {While the collective impact of marine viruses has become more apparent over the last decade, a deeper understanding of virus-host dynamics and the role of viruses in nutrient cycling would benefit from direct observations at the single-virus level. We describe two new complementary approaches - stable isotope probing coupled with nanoscale secondary ion mass spectrometry (nanoSIMS) and fluorescence-based biorthogonal non-canonical amino acid tagging (BONCAT) - for studying the activity and biogeochemical influence of marine viruses. These tools were developed and tested using several ecologically relevant model systems (Emiliania huxleyi/EhV207, Synechococcus sp. WH8101/Syn1 and Escherichia coli/T7). By resolving carbon and nitrogen enrichment in viral particles, we demonstrate the power of nanoSIMS tracer experiments in obtaining quantitative estimates for the total number of viruses produced directly from a particular production pathway (by isotopically labelling host substrates). Additionally, we show through laboratory experiments and a pilot field study that BONCAT can be used to directly quantify viral production (via epifluorescence microscopy) with minor sample manipulation and no dependency on conversion factors. This technique can also be used to detect newly synthesized viral proteins. Together these tools will help fill critical gaps in our understanding of the biogeochemical impact of viruses in the ocean.}, } @article {pmid29159926, year = {2018}, author = {Sebastián, M and Auguet, JC and Restrepo-Ortiz, CX and Sala, MM and Marrasé, C and Gasol, JM}, title = {Deep ocean prokaryotic communities are remarkably malleable when facing long-term starvation.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {713-723}, doi = {10.1111/1462-2920.14002}, pmid = {29159926}, issn = {1462-2920}, abstract = {The bathypelagic ocean is one of the largest ecosystems on Earth and sustains half of the ocean's microbial activity. This microbial activity strongly relies on surface-derived particles, but there is growing evidence that the carbon released through solubilization of these particles may not be sufficient to meet the energy demands of deep ocean prokaryotes. To explore how bathypelagic prokaryotes respond to the absence of external inputs of carbon, we followed the long-term (1 year) dynamics of an enclosed community. Despite the lack of external energy supply, we observed a continuous succession of active prokaryotic phylotypes, which was driven by recruitment of taxa from the seed bank (i.e., initially rare operational taxonomic units [OTUs]). A single OTU belonging to Marine Group I of Thaumarchaeota, which was originally rare, dominated the microbial community for ∼ 4 months and played a fundamental role in this succession likely by introducing new organic carbon through chemolithoautotrophy. This carbon presumably produced a priming effect, because after the decline of Thaumarchaeota, the diversity and metabolic potential of the community increased back to the levels present at the start of the experiment. Our study demonstrates the profound versatility of deep microbial communities when facing organic carbon deprivation.}, } @article {pmid29159878, year = {2018}, author = {Hoffmann, T and Warmbold, B and Smits, SHJ and Tschapek, B and Ronzheimer, S and Bashir, A and Chen, C and Rolbetzki, A and Pittelkow, M and Jebbar, M and Seubert, A and Schmitt, L and Bremer, E}, title = {Arsenobetaine: an ecophysiologically important organoarsenical confers cytoprotection against osmotic stress and growth temperature extremes.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {305-323}, doi = {10.1111/1462-2920.13999}, pmid = {29159878}, issn = {1462-2920}, abstract = {Arsenic, a highly cytotoxic and cancerogenic metalloid, is brought into the biosphere through geochemical sources and anthropogenic activities. A global biogeochemical arsenic biotransformation cycle exists in which inorganic arsenic species are transformed into organoarsenicals, which are subsequently mineralized again into inorganic arsenic compounds. Microorganisms contribute to this biotransformation process greatly and one of the organoarsenicals synthesized and degraded in this cycle is arsenobetaine. Its nitrogen-containing homologue glycine betaine is probably the most frequently used compatible solute on Earth. Arsenobetaine is found in marine and terrestrial habitats and even in deep-sea hydrothermal vent ecosystems. Despite its ubiquitous occurrence, the biological function of arsenobetaine has not been comprehensively addressed. Using Bacillus subtilis as a well-understood platform for the study of microbial osmostress adjustment systems, we ascribe here to arsenobetaine both a protective function against high osmolarity and a cytoprotective role against extremes in low and high growth temperatures. We define a biosynthetic route for arsenobetaine from the precursor arsenocholine that relies on enzymes and genetic regulatory circuits for glycine betaine formation from choline, identify the uptake systems for arsenobetaine and arsenocholine, and describe crystal structures of ligand-binding proteins from the OpuA and OpuB ABC transporters complexed with either arsenobetaine or arsenocholine.}, } @article {pmid29159858, year = {2018}, author = {Piwosz, K and Kaftan, D and Dean, J and Šetlík, J and Koblížek, M}, title = {Nonlinear effect of irradiance on photoheterotrophic activity and growth of the aerobic anoxygenic phototrophic bacterium Dinoroseobacter shibae.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {724-733}, doi = {10.1111/1462-2920.14003}, pmid = {29159858}, issn = {1462-2920}, abstract = {Aerobic anoxygenic photosynthetic bacteria are an important component of marine microbial communities. They produce energy in light using bacteriochlorophyll a containing photosystems. This extra energy provides an advantage over purely heterotrophic bacteria. One of the most intensively studied AAP bacteria is Dinoroseobacter shibae, a member of the environmentally important Roseobacter clade. Light stimulates its growth and metabolism, but the effect of light intensity remains unclear. Here, we show that an increase in biomass along an irradiance gradient followed the exponential rise to the maximum curve, with saturation at about 300 µmol photons m-2 s-1 , without any inhibition at light intensities up to 600 µmol photons m-2 s-1 . The cells adapted to higher irradiance by reducing pigmentation and increasing the electron transfer rate. This additional energy allowed D. shibae to redirect the metabolism of organic carbon sources such as glucose, leucine, glutamate, acetate and pyruvate toward anabolism, resulting in a twofold increase of their assimilation rates. We provide equations that can be feasibly incorporated into the existing model of D. shibae metabolism to further advance our understanding of the role of photoheterotrophy in the ocean.}, } @article {pmid29159690, year = {2018}, author = {Correia, AML and Lira, SP and Assis, MA and Rodrigues, A}, title = {Fungal Endophyte Communities in Begonia Species from the Brazilian Atlantic Rainforest.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {441-449}, pmid = {29159690}, issn = {1432-0991}, support = {2013/50228-8//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2014/15760-3//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; 2014/12021-5//Fundação de Amparo à Pesquisa do Estado de São Paulo/ ; }, mesh = {Begoniaceae/*microbiology ; Biodiversity ; Brazil ; Endophytes/classification/genetics/*isolation & purification ; Fungi/classification/genetics/*isolation & purification ; Phylogeny ; Rainforest ; }, abstract = {Tropical plants represent hotspots of endophytic fungal species diversity. Based on culture-dependent methods, we evaluated the endophytic fungal communities in leaves of three plant species found in the Brazilian Atlantic Rainforest: Begonia fischeri, Begonia olsoniae, and Begonia venosa. These species are found in two distant sites: a continental region and an insular area. A total of 426 fungal endophytes in 19 genera were isolated in pure culture including Colletotrichum (51.6% of isolates) and Diaporthe (22.5%) as the most abundant, followed by Phyllosticta (3.5%), Neopestalotiopsis (1.8%), Stagonospora (1.8%), and Nigrospora (1.6%) among the genera found in minor abundance. The diversity and composition of fungal taxa differed across plant hosts. Richness and diversity of fungi were higher in B. fischeri in comparison to B. olsoniae and B. venosa. Discriminatory analysis revealed that fungal communities are structured according to hosts, which means that each plant species had its distinct endophytic communities, but dominated by common fungal taxa. This is the first study to report fungal endophytes in begonia leaves and characterize their communities.}, } @article {pmid29159689, year = {2018}, author = {Tanapichatsakul, C and Monggoot, S and Gentekaki, E and Pripdeevech, P}, title = {Antibacterial and Antioxidant Metabolites of Diaporthe spp. Isolated from Flowers of Melodorum fruticosum.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {476-483}, pmid = {29159689}, issn = {1432-0991}, support = {PHD/0184/2559//Thailand Research Fund/ ; }, mesh = {Anti-Bacterial Agents/chemistry/metabolism/*pharmacology ; Antioxidants/chemistry/metabolism/*pharmacology ; Ascomycota/*chemistry/genetics/isolation & purification/metabolism ; Endophytes/*chemistry/genetics/isolation & purification/metabolism ; Flowers/*microbiology ; Magnoliaceae/*microbiology ; Microbial Sensitivity Tests ; Plants, Medicinal/microbiology ; Staphylococcus aureus/drug effects ; }, abstract = {Fifty-two strains of endophytic fungi were isolated from flowers of the medicinal plant Melodorum fruticosum. Seven genera were identified including Alternaria, Aspergillus, Colletotrichum, Diaporthe, Fusarium, Greeneria and Nigrospora. All strains were cultured for 30 days and further macerated in ethyl acetate solvent for 3 days. The obtained fungal extracts were examined for antibacterial activity using agar disc diffusion against nine pathogenic bacteria: Staphylococcus aureus, Bacillus subtilis, B. cereus, Klebsiella pneumoniae, Pseudomonas aeruginosa, Escherichia coli, Shigella flexneri, Vibrio cholerae and V. parahaemolyticus. Forty-three fungal extracts exhibited antibacterial activity against at least one tested pathogen. The antioxidant properties of all extracts were also investigated by DPPH scavenging assay. Sixteen extracts displayed high antioxidant capacity (IC50 ranging from 10 to 50 µg/mL) when compared to the gallic acid and trolox standards (IC50 of 12.46 and 2.55 µg/mL, respectively). The crude extracts of Diaporthe sp. MFLUCC16-0682 and Diaporthe sp. MFLUCC16-0693 exhibited notable antibacterial and antioxidant activities. Analysis of chemical composition using gas chromatography-mass spectrometry suggested that the observed antibacterial activity of the two Diaporthe spp. was possibly due to the presence of abienol, 4-methoxy stilbene, phenethyl cinnamate and 2Z,6Z-farnesal, while their potential antioxidant activity could be attributed to phenolic compounds, such as benzene acetaldehyde, benzyl benzoate, salicylaldehyde, benzoin and benzyl cinnamate. The results suggest that the genus Diaporthe is a potential source of metabolites that can be used in a variety of applications.}, } @article {pmid29159671, year = {2018}, author = {Dobigny, G and Robinson, TJ and Veyrunes, F}, title = {Janice Britton-Davidian (1950-2017).}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {3}, pages = {113-114}, doi = {10.1007/s10577-017-9568-6}, pmid = {29159671}, issn = {1573-6849}, } @article {pmid29159670, year = {2018}, author = {Tseng, SH and Peng, SF and Cheng, YM}, title = {Analysis of B chromosome nondisjunction induced by the r-X1 deficiency in maize.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {3}, pages = {153-162}, pmid = {29159670}, issn = {1573-6849}, support = {MOST 104-2311-B-005-012-MY3//Ministry of Science and Technology, Taiwan/International ; }, mesh = {Cell Division/*genetics ; Chromosomes, Plant/*genetics/metabolism ; Zea mays/*genetics/metabolism ; }, abstract = {The maize B chromosome typically undergoes nondisjunction during the second microspore division. For normal A chromosomes, the r-X1 deficiency in maize can induce nondisjunction during the second megaspore and first microspore divisions. However, it is not known whether the r-X1 deficiency also induces nondisjunction of the maize B chromosome during these cell divisions. To answer this question, chromosome numbers were determined in the progeny of r-X1/R-r female parents carrying two B chromosomes. Some of the r-X1-lacking progeny (21.2%) contained zero or two B chromosomes. However, a much higher percentage of the r-X1-containing progeny (43.4%) exhibited zero or two B chromosomes, but none displayed more than two B chromosomes. Thus, the results indicated that the r-X1 deficiency could also induce nondisjunction of the B chromosome during the second megaspore division; moreover, the B chromosome in itself could undergo nondisjunction during the same division. In addition, pollen grains from plants with two B chromosomes lacking or exhibiting the r-X1 deficiency were compared via pollen fluorescence in situ hybridization (FISH) using a B chromosome-specific probe. The results revealed that the r-X1 deficiency could induce the occurrence of B chromosome nondisjunction during the first microspore division and that the B chromosome in itself could undergo nondisjunction during the same division at a lower frequency. Our data shed more light on the behavior of the maize B chromosome during cell division.}, } @article {pmid29158606, year = {2018}, author = {Ramirez, KS and Knight, CG and de Hollander, M and Brearley, FQ and Constantinides, B and Cotton, A and Creer, S and Crowther, TW and Davison, J and Delgado-Baquerizo, M and Dorrepaal, E and Elliott, DR and Fox, G and Griffiths, RI and Hale, C and Hartman, K and Houlden, A and Jones, DL and Krab, EJ and Maestre, FT and McGuire, KL and Monteux, S and Orr, CH and van der Putten, WH and Roberts, IS and Robinson, DA and Rocca, JD and Rowntree, J and Schlaeppi, K and Shepherd, M and Singh, BK and Straathof, AL and Bhatnagar, JM and Thion, C and van der Heijden, MGA and de Vries, FT}, title = {Detecting macroecological patterns in bacterial communities across independent studies of global soils.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {189-196}, doi = {10.1038/s41564-017-0062-x}, pmid = {29158606}, issn = {2058-5276}, support = {G1100076//Medical Research Council/United Kingdom ; }, abstract = {The emergence of high-throughput DNA sequencing methods provides unprecedented opportunities to further unravel bacterial biodiversity and its worldwide role from human health to ecosystem functioning. However, despite the abundance of sequencing studies, combining data from multiple individual studies to address macroecological questions of bacterial diversity remains methodically challenging and plagued with biases. Here, using a machine-learning approach that accounts for differences among studies and complex interactions among taxa, we merge 30 independent bacterial data sets comprising 1,998 soil samples from 21 countries. Whereas previous meta-analysis efforts have focused on bacterial diversity measures or abundances of major taxa, we show that disparate amplicon sequence data can be combined at the taxonomy-based level to assess bacterial community structure. We find that rarer taxa are more important for structuring soil communities than abundant taxa, and that these rarer taxa are better predictors of community structure than environmental factors, which are often confounded across studies. We conclude that combining data from independent studies can be used to explore bacterial community dynamics, identify potential 'indicator' taxa with an important role in structuring communities, and propose hypotheses on the factors that shape bacterial biogeography that have been overlooked in the past.}, } @article {pmid29158605, year = {2018}, author = {Pollpeter, D and Parsons, M and Sobala, AE and Coxhead, S and Lang, RD and Bruns, AM and Papaioannou, S and McDonnell, JM and Apolonia, L and Chowdhury, JA and Horvath, CM and Malim, MH}, title = {Deep sequencing of HIV-1 reverse transcripts reveals the multifaceted antiviral functions of APOBEC3G.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {220-233}, pmid = {29158605}, issn = {2058-5276}, support = {//Wellcome Trust/United Kingdom ; G1000196//Medical Research Council/United Kingdom ; MR/M001199/1//Medical Research Council/United Kingdom ; }, abstract = {Following cell entry, the RNA genome of HIV-1 is reverse transcribed into double-stranded DNA that ultimately integrates into the host-cell genome to establish the provirus. These early phases of infection are notably vulnerable to suppression by a collection of cellular antiviral effectors, called restriction or resistance factors. The host antiviral protein APOBEC3G (A3G) antagonizes the early steps of HIV-1 infection through the combined effects of inhibiting viral cDNA production and cytidine-to-uridine-driven hypermutation of this cDNA. In seeking to address the underlying molecular mechanism for inhibited cDNA synthesis, we developed a deep sequencing strategy to characterize nascent reverse transcription products and their precise 3'-termini in HIV-1 infected T cells. Our results demonstrate site- and sequence-independent interference with reverse transcription, which requires the specific interaction of A3G with reverse transcriptase itself. This approach also established, contrary to current ideas, that cellular uracil base excision repair (UBER) enzymes target and cleave A3G-edited uridine-containing viral cDNA. Together, these findings yield further insights into the regulatory interplay between reverse transcriptase, A3G and cellular DNA repair machinery, and identify the suppression of HIV-1 reverse transcriptase by a directly interacting host protein as a new cell-mediated antiviral mechanism.}, } @article {pmid29158604, year = {2018}, author = {Jurado, KA and Yockey, LJ and Wong, PW and Lee, S and Huttner, AJ and Iwasaki, A}, title = {Antiviral CD8 T cells induce Zika-virus-associated paralysis in mice.}, journal = {Nature microbiology}, volume = {3}, number = {2}, pages = {141-147}, pmid = {29158604}, issn = {2058-5276}, support = {T32 AI007019/AI/NIAID NIH HHS/United States ; T32 GM007205/GM/NIGMS NIH HHS/United States ; }, abstract = {Zika virus (ZIKV) is an emerging, mosquito-borne RNA virus. The rapid spread of ZIKV within the Americas has unveiled microcephaly 1 and Guillain-Barré syndrome2,3 as ZIKV-associated neurological complications. Recent reports have also indicated other neurological manifestations to be associated with ZIKV, including myelitis 4 , meningoencephalitis 5 and fatal encephalitis 6 . Here, we investigate the neuropathogenesis of ZIKV infection in type I interferon receptor IFNAR knockout (Ifnar1 -/-) mice, an infection model that exhibits high viral burden within the central nervous system. We show that systemic spread of ZIKV from the site of infection to the brain requires Ifnar1 deficiency in the haematopoietic compartment. However, spread of ZIKV within the central nervous system is supported by Ifnar1-deficient non-haematopoietic cells. Within this context, ZIKV infection of astrocytes results in breakdown of the blood-brain barrier and a large influx of CD8+ effector T cells. We also find that antiviral activity of CD8+ T cells within the brain markedly limits ZIKV infection of neurons, but, as a consequence, instigates ZIKV-associated paralysis. Taken together, our study uncovers mechanisms underlying ZIKV neuropathogenesis within a susceptible mouse model and suggests blood-brain barrier breakdown and T-cell-mediated neuropathology as potential underpinnings of ZIKV-associated neurological complications in humans.}, } @article {pmid29158556, year = {2018}, author = {Liu, H and Huang, J and Sun, X and Li, J and Hu, Y and Yu, L and Liti, G and Tian, D and Hurst, LD and Yang, S}, title = {Tetrad analysis in plants and fungi finds large differences in gene conversion rates but no GC bias.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {164-173}, pmid = {29158556}, issn = {2397-334X}, support = {669207//European Research Council/International ; }, mesh = {Arabidopsis/*genetics ; *Base Composition ; Chlamydomonas/*genetics ; *Gene Conversion ; Meiosis ; Neurospora/*genetics ; Saccharomyces/*genetics ; Spores, Fungal/genetics ; Whole Genome Sequencing ; }, abstract = {GC-favouring gene conversion enables fixation of deleterious alleles, disturbs tests of natural selection and potentially explains both the evolution of recombination as well as the commonly reported intragenomic correlation between G+C content and recombination rate. In addition, gene conversion disturbs linkage disequilibrium, potentially affecting the ability to detect causative variants. However, the importance and generality of these effects is unresolved, not simply because direct analyses are technically challenging but also because previous within- and between-species discrepant results can be hard to appraise owing to methodological differences. Here we report results of methodologically uniform whole-genome sequencing of all tetrad products in Saccharomyces, Neurospora, Chlamydomonas and Arabidopsis. The proportion of polymorphic markers converted varies over three orders of magnitude between species (from 2% of markers converted in yeast to only ~0.005% in the two plants) with at least 87.5% of the variance in per tetrad conversion rates being between species. This is largely due to differences in recombination rate and median tract length. Despite three of the species showing a positive GC-recombination correlation, there is no significant net AT→GC conversion bias in any of the species, despite relatively high resolution in the two taxa (Saccharomyces and Neurospora) with relatively common gene conversion. The absence of a GC bias means that: (1) there should be no presumption that gene conversion is GC biased, or (2) that a GC-recombination correlation necessarily implies biased gene conversion, (3) K a/K s tests should be unaffected in these species and (4) it is unlikely that gene conversion explains the evolution of recombination.}, } @article {pmid29158555, year = {2018}, author = {Rudman, SM and Barbour, MA and Csilléry, K and Gienapp, P and Guillaume, F and Hairston, NG and Hendry, AP and Lasky, JR and Rafajlović, M and Räsänen, K and Schmidt, PS and Seehausen, O and Therkildsen, NO and Turcotte, MM and Levine, JM}, title = {What genomic data can reveal about eco-evolutionary dynamics.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {9-15}, doi = {10.1038/s41559-017-0385-2}, pmid = {29158555}, issn = {2397-334X}, mesh = {*Biological Evolution ; Ecology ; *Ecosystem ; *Genome ; Genomics ; }, abstract = {Recognition that evolution operates on the same timescale as ecological processes has motivated growing interest in eco-evolutionary dynamics. Nonetheless, generating sufficient data to test predictions about eco-evolutionary dynamics has proved challenging, particularly in natural contexts. Here we argue that genomic data can be integrated into the study of eco-evolutionary dynamics in ways that deepen our understanding of the interplay between ecology and evolution. Specifically, we outline five major questions in the study of eco-evolutionary dynamics for which genomic data may provide answers. Although genomic data alone will not be sufficient to resolve these challenges, integrating genomic data can provide a more mechanistic understanding of the causes of phenotypic change, help elucidate the mechanisms driving eco-evolutionary dynamics, and lead to more accurate evolutionary predictions of eco-evolutionary dynamics in nature.}, } @article {pmid29158554, year = {2018}, author = {Kardos, M and Åkesson, M and Fountain, T and Flagstad, Ø and Liberg, O and Olason, P and Sand, H and Wabakken, P and Wikenros, C and Ellegren, H}, title = {Genomic consequences of intensive inbreeding in an isolated wolf population.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {124-131}, doi = {10.1038/s41559-017-0375-4}, pmid = {29158554}, issn = {2397-334X}, mesh = {Animals ; *Genome ; *Inbreeding ; Norway ; Polymorphism, Single Nucleotide ; Sweden ; Wolves/*genetics ; }, abstract = {Inbreeding (mating between relatives) is a major concern for conservation as it decreases individual fitness and can increase the risk of population extinction. We used whole-genome resequencing of 97 grey wolves (Canis lupus) from the highly inbred Scandinavian wolf population to identify 'identical-by-descent' (IBD) chromosome segments as runs of homozygosity (ROH). This gave the high resolution required to precisely measure realized inbreeding as the IBD fraction of the genome in ROH (F ROH). We found a striking pattern of complete or near-complete homozygosity of entire chromosomes in many individuals. The majority of individual inbreeding was due to long IBD segments (>5 cM) originating from ancestors ≤10 generations ago, with 10 genomic regions showing very few ROH and forming candidate regions for containing loci contributing strongly to inbreeding depression. Inbreeding estimated with an extensive pedigree (F P) was strongly correlated with realized inbreeding measured with the entire genome (r 2 = 0.86). However, inbreeding measured with the whole genome was more strongly correlated with multi-locus heterozygosity estimated with as few as 500 single nucleotide polymorphisms, and with F ROH estimated with as few as 10,000 single nucleotide polymorphisms, than with F P. These results document in fine detail the genomic consequences of intensive inbreeding in a population of conservation concern.}, } @article {pmid29158553, year = {2018}, author = {Valverde, S and Piñero, J and Corominas-Murtra, B and Montoya, J and Joppa, L and Solé, R}, title = {The architecture of mutualistic networks as an evolutionary spandrel.}, journal = {Nature ecology & evolution}, volume = {2}, number = {1}, pages = {94-99}, pmid = {29158553}, issn = {2397-334X}, support = {726176//European Research Council/International ; }, mesh = {*Biological Evolution ; Models, Biological ; *Symbiosis ; }, abstract = {Mutualistic networks have been shown to involve complex patterns of interactions among animal and plant species, including a widespread presence of nestedness. The nested structure of these webs seems to be positively correlated with higher diversity and resilience. Moreover, these webs exhibit marked measurable structural patterns, including broad distributions of connectivity, strongly asymmetrical interactions and hierarchical organization. Hierarchical organization is an especially interesting property, since it is positively correlated with biodiversity and network resilience, thus suggesting potential selection processes favouring the observed web organization. However, here we show that all these structural quantitative patterns-and nestedness in particular-can be properly explained by means of a very simple dynamical model of speciation and divergence with no selection-driven coevolution of traits. The agreement between observed and modelled networks suggests that the patterns displayed by real mutualistic webs might actually represent evolutionary spandrels.}, } @article {pmid29158412, year = {2018}, author = {Khan, SK and Yadav, PS and Elliott, G and Hu, DZ and Xu, R and Yang, Y}, title = {Induced GnasR201H expression from the endogenous Gnas locus causes fibrous dysplasia by up-regulating Wnt/β-catenin signaling.}, journal = {Proceedings of the National Academy of Sciences of the United States of America}, volume = {115}, number = {3}, pages = {E418-E427}, pmid = {29158412}, issn = {1091-6490}, support = {R01 AR070877/AR/NIAMS NIH HHS/United States ; R01 DE025866/DE/NIDCR NIH HHS/United States ; }, mesh = {Cell Differentiation ; Chromogranins/genetics/*metabolism ; Fibrous Dysplasia of Bone/*genetics ; GTP-Binding Protein alpha Subunits, Gs/genetics/*metabolism ; Gene Expression Regulation ; Humans ; Mesenchymal Stem Cells/physiology ; Mutation ; Osteoblasts/physiology ; Signal Transduction ; Up-Regulation ; Wnt Proteins/genetics/*metabolism ; beta Catenin/genetics/*metabolism ; }, abstract = {Fibrous dysplasia (FD; Online Mendelian Inheritance in Man no. 174800) is a crippling skeletal disease caused by activating mutations of the GNAS gene, which encodes the stimulatory G protein Gαs FD can lead to severe adverse conditions such as bone deformity, fracture, and severe pain, leading to functional impairment and wheelchair confinement. So far there is no cure, as the underlying molecular and cellular mechanisms remain largely unknown and the lack of appropriate animal models has severely hampered FD research. Here we have investigated the cellular and molecular mechanisms underlying FD and tested its potential treatment by establishing a mouse model in which the human FD mutation (R201H) has been conditionally knocked into the corresponding mouse Gnas locus. We found that the germ-line FD mutant was embryonic lethal, and Cre-induced Gnas FD mutant expression in early osteochondral progenitors, osteoblast cells, or bone marrow stromal cells (BMSCs) recapitulated FD features. In addition, mosaic expression of FD mutant Gαs in BMSCs induced bone marrow fibrosis both cell autonomously and non-cell autonomously. Furthermore, Wnt/β-catenin signaling was up-regulated in FD mutant mouse bone and BMSCs undergoing osteogenic differentiation, as we have found in FD human tissue previously. Reduction of Wnt/β-catenin signaling by removing one Lrp6 copy in an FD mutant line significantly rescued the phenotypes. We demonstrate that induced expression of the FD Gαs mutant from the mouse endogenous Gnas locus exhibits human FD phenotypes in vivo, and that inhibitors of Wnt/β-catenin signaling may be repurposed for treating FD and other bone diseases caused by Gαs activation.}, } @article {pmid29158320, year = {2018}, author = {Ringelhan, M and McKeating, JA and Protzer, U}, title = {Correction to 'Viral hepatitis and liver cancer'.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, doi = {10.1098/rstb.2017.0339}, pmid = {29158320}, issn = {1471-2970}, } @article {pmid29158319, year = {2018}, author = {Pink, RC and Elmusrati, AA and Lambert, D and Carter, DRF}, title = {Royal Society Scientific Meeting: Extracellular vesicles in the tumour microenvironment.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158319}, issn = {1471-2970}, mesh = {Extracellular Vesicles/*physiology ; Humans ; Neoplasms/*physiopathology ; Tumor Microenvironment/*physiology ; }, abstract = {Cancer cells do not grow as an isolated homogeneous mass; tumours are, in fact, complex and heterogeneous collections of cancer and surrounding stromal cells, collectively termed the tumour microenvironment. The interaction between cancer cells and stromal cells in the tumour microenvironment has emerged as a key concept in the regulation of cancer progression. Understanding the intercellular dialogue in the tumour microenvironment is therefore an important goal. One aspect of this dialogue that has not been appreciated until recently is the role of extracellular vesicles (EVs). EVs are small vesicles released by cells under both normal and pathological conditions; they can transfer biological molecules between cells leading to changes in phenotype. EVs have emerged as important regulators of biological processes and can be dysregulated in diseases such as cancer; rapidly growing interest in their biology and therapeutic potential led to the Royal Society hosting a Scientific Meeting to explore the roles of EVs in the tumour microenvironment. This cross-disciplinary meeting explored examples of how aberrant crosstalk between tumour and stromal cells can promote cancer progression, and how such signalling can be targeted for diagnostic, prognostic and therapeutic benefit. In this review, and the special edition of Philosophical Transactions of the Royal Society B that follows, we will provide an overview of the content and outcomes of this exciting meeting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158318, year = {2018}, author = {Samuel, P and Mulcahy, LA and Furlong, F and McCarthy, HO and Brooks, SA and Fabbri, M and Pink, RC and Carter, DRF}, title = {Cisplatin induces the release of extracellular vesicles from ovarian cancer cells that can induce invasiveness and drug resistance in bystander cells.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158318}, issn = {1471-2970}, mesh = {Antineoplastic Agents/*pharmacology ; Cell Line, Tumor ; Cisplatin/*pharmacology ; *Drug Resistance ; Extracellular Vesicles/*physiology ; Female ; Humans ; Ovarian Neoplasms/*physiopathology ; }, abstract = {Ovarian cancer has a poor overall survival that is partly caused by resistance to drugs such as cisplatin. Resistance can be acquired as a result of changes to the tumour or due to altered interactions within the tumour microenvironment. Extracellular vesicles (EVs), small lipid-bound vesicles that are loaded with macromolecular cargo and released by cells, are emerging as mediators of communication in the tumour microenvironment. We previously showed that EVs mediate the bystander effect, a phenomenon in which stressed cells can communicate with neighbouring naive cells leading to various effects including DNA damage; however, the role of EVs released following cisplatin treatment has not been tested. Here we show that treatment of cells with cisplatin led to the release of EVs that could induce invasion and increased resistance when taken up by bystander cells. This coincided with changes in p38 and JNK signalling, suggesting that these pathways may be involved in mediating the effects. We also show that EV uptake inhibitors could prevent this EV-mediated adaptive response and thus sensitize cells in vitro to the effects of cisplatin. Our results suggest that preventing pro-tumourigenic EV cross-talk during chemotherapy is a potential therapeutic target for improving outcome in ovarian cancer patients.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158317, year = {2018}, author = {Gregory, CD and Paterson, M}, title = {An apoptosis-driven 'onco-regenerative niche': roles of tumour-associated macrophages and extracellular vesicles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158317}, issn = {1471-2970}, mesh = {Apoptosis/*physiology ; Extracellular Vesicles/*physiology ; Macrophages/*physiology ; Neoplasms/*physiopathology ; Tumor Microenvironment/*physiology ; }, abstract = {The cell-death programme, apoptosis, is well established as a tumour suppressor mechanism. Paradoxically, high levels of apoptosis in tumours are closely coupled with poor prognosis. Indeed, where it has been studied, cell loss is a striking feature of high-grade cancers, illustrating the importance of considering malignant disease as an imbalance between cell gain and cell loss that favours cell gain rather than as a unidirectional disorder of cell gain alone. In addition to orchestrating cell loss, apoptosis can signal regenerative responses-for example compensatory proliferation-in neighbouring cells. Accumulating evidence suggests that normal tissue repair and regenerative processes are hijacked in the malignant tissue microenvironment such that cancer may be likened to a 'wound that fails to stop repairing'. We have proposed that a critical requirement for the successful growth, progression and re-growth of malignant tumours is a complex milieu, conceptually termed the 'onco-regenerative niche', which is composed, in addition to transformed neoplastic cells, of a network of normal cells and factors activated as if in tissue repair and regeneration. Our work is based around the hypothesis that tumour cell apoptosis, macrophage activation and endothelial activation are key, interlinked elements of the onco-regenerative niche and that apoptotic tumour cell-derived extracellular vesicles provide critical intercellular communication vehicles of the niche. In aggressive B-cell lymphoma, tumour cell apoptosis promotes both angiogenesis and the accumulation of pro-tumour macrophages in the lymphoma microenvironment. Furthermore, apoptotic lymphoma-derived extracellular vesicles have potent pro-tumour potential. These findings have important implications for the roles of apoptosis in regulation of malignant diseases and for the efficacy of apoptosis-inducing anti-cancer therapies.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158316, year = {2018}, author = {O'Loghlen, A}, title = {Role for extracellular vesicles in the tumour microenvironment.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158316}, issn = {1471-2970}, mesh = {Cell Communication/*physiology ; Extracellular Vesicles/*physiology ; Humans ; Tumor Microenvironment/*physiology ; }, abstract = {Extracellular vesicles (EVs) are small-membrane vesicles secreted by most cells types with the role to provide intercellular communication both locally and systemically. The transfer of their content between cells, which includes nucleic acids, proteins and lipids, confers the means for these interactions and induces significant cellular behaviour changes in the receiving cell. EVs are implicated in the regulation of numerous physiological and pathological processes, including development and neurological and cardiovascular diseases. Importantly, it has been shown that EV signalling is essential in almost all the steps necessary for the progress of carcinomas, from primary tumours to metastasis. In this review, we will focus on the latest findings for EV biology in relation to cancer progression and the tumour microenvironment.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158315, year = {2018}, author = {Fabbri, M}, title = {MicroRNAs and miRceptors: a new mechanism of action for intercellular communication.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158315}, issn = {1471-2970}, support = {R01 CA215753/CA/NCI NIH HHS/United States ; }, mesh = {Cell Communication/*physiology ; Extracellular Vesicles/*physiology ; Humans ; MicroRNAs/*physiology ; Tumor Microenvironment/*physiology ; }, abstract = {MicroRNAs (miRs) are small non-coding RNAs (ncRNAs) that control the expression of target genes by modulating (usually inhibiting) their translation into proteins. This 'traditional' mechanism of action of miRs has been recently challenged by new discoveries pointing towards a role of miRs as 'hormones', capable of binding to proteic receptors (miRceptors) and triggering their downstream signalling pathways. These findings harbour particular significance within the tumour microenvironment (TME), defined as the variety of non-cancerous cells surrounding cancer cells, but are relevant also for other diseases. In recent years it has become clearer that the TME does not passively assist the growth of cancer cells but contributes to its biology. Some of the mediators of the intercellular communication between cancer cells and TME are miRs shuttled within exosomes, a subtype of cellular released extracellular vesicles. This article will highlight the most recent findings on the biological implications of miR-miRceptor interactions for the biology of the TME and other diseases, and will provide some perspectives on the future development of this fascinating research.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158314, year = {2018}, author = {Robado de Lope, L and Alcíbar, OL and Amor López, A and Hergueta-Redondo, M and Peinado, H}, title = {Tumour-adipose tissue crosstalk: fuelling tumour metastasis by extracellular vesicles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158314}, issn = {1471-2970}, mesh = {Adipose Tissue/*physiopathology ; Animals ; Breast Neoplasms/etiology/physiopathology ; Extracellular Vesicles/*physiology ; Female ; Humans ; Melanoma/etiology/physiopathology ; Mice ; Neoplasm Metastasis/*physiopathology ; Obesity/*physiopathology ; Ovarian Neoplasms/etiology/physiopathology ; Tumor Microenvironment/*physiology ; }, abstract = {During metastasis, tumour cells must communicate with their microenvironment by secreted soluble factors and extracellular vesicles. Different stromal cell types (e.g. bone marrow-derived cells, endothelial cells and fibroblasts) influence the growth and progression of tumours. In recent years, interest has extended to other cell types in the tumour microenvironment such as adipocytes and adipose tissue-derived mesenchymal stem cells. Indeed, obesity is becoming pandemic in some developing countries and it is now considered to be a risk factor for cancer progression. However, the true impact of obesity on the metastatic behaviour of tumours is still not yet fully understood. In this 'Perspective' article, we will discuss the potential influence of obesity on tumour metastasis, mainly in melanoma, breast and ovarian cancer. We summarize the main mechanisms involved with special attention to the role of extracellular vesicles in this process. We envisage that besides having a direct impact on tumour cells, obesity systemically preconditions the tumour microenvironment for future metastasis by favouring the formation of pro-inflammatory niches.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158313, year = {2018}, author = {Ohyashiki, JH and Umezu, T and Ohyashiki, K}, title = {Extracellular vesicle-mediated cell-cell communication in haematological neoplasms.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158313}, issn = {1471-2970}, mesh = {Cell Communication/*physiology ; Extracellular Vesicles/*physiology ; Hematologic Neoplasms/*physiopathology ; Humans ; Leukemia/*physiopathology ; Multiple Myeloma/*physiopathology ; Tumor Microenvironment/*physiology ; }, abstract = {Crosstalk between bone marrow tumour cells and surrounding cells, including bone marrow mesenchymal stromal cells (BM-MSCs), endothelial cells and immune cells, is important for tumour growth in haematological neoplasms. In addition to conventional signalling pathways, extracellular vesicles (EVs), which are endosome-derived vesicles containing proteins, mRNAs, lipids and miRNAs, can facilitate modulation of the bone marrow microenvironment without directly contacting non-tumourous cells. In this review, we discuss the current understanding of EV-mediated cell-cell communication in haematological neoplasms, particularly leukaemia and multiple myeloma. We highlight the actions of tumour and BM-MSC EVs in multiple myeloma. The origin of EVs, their tropism and mechanism of EV transfer are emerging issues that need to be addressed in EV-mediated cell-cell communication in haematological neoplasms.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158312, year = {2018}, author = {Salo, T and Dourado, MR and Sundquist, E and Apu, EH and Alahuhta, I and Tuomainen, K and Vasara, J and Al-Samadi, A}, title = {Organotypic three-dimensional assays based on human leiomyoma-derived matrices.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158312}, issn = {1471-2970}, mesh = {*Carcinogenesis ; Extracellular Matrix/*physiology ; Extracellular Vesicles/*physiology ; Humans ; Leiomyoma/*physiopathology ; Tumor Microenvironment/*physiology ; }, abstract = {Alongside cancer cells, tumours exhibit a complex stroma containing a repertoire of cells, matrix molecules and soluble factors that actively crosstalk between each other. Recognition of this multifaceted concept of the tumour microenvironment (TME) calls for authentic TME mimetics to study cancer in vitro Traditionally, tumourigenesis has been investigated in non-human, three-dimensional rat type I collagen containing organotypic discs or by means of mouse sarcoma-derived gel, such as Matrigel® However, the molecular compositions of these simplified assays do not properly simulate human TME. Here, we review the main properties and benefits of using human leiomyoma discs and their matrix Myogel for in vitro assays. Myoma discs are practical for investigating the invasion of cancer cells, as are cocultures of cancer and stromal cells in a stiff, hypoxic TME mimetic. Myoma discs contain soluble factors and matrix molecules commonly present in neoplastic stroma. In Transwell, IncuCyte, spheroid and sandwich assays, cancer cells move faster and form larger colonies in Myogel than in Matrigel® Additionally, Myogel can replace Matrigel® in hanging-drop and tube-formation assays. Myogel also suits three-dimensional drug testing and extracellular vesicle interactions. To conclude, we describe the application of our myoma-derived matrices in 3D in vitro cancer assays.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158311, year = {2018}, author = {Dörsam, B and Reiners, KS and von Strandmann, EP}, title = {Cancer-derived extracellular vesicles: friend and foe of tumour immunosurveillance.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158311}, issn = {1471-2970}, mesh = {Extracellular Vesicles/*immunology ; *Immunologic Surveillance ; Neoplasms/*physiopathology ; Tumor Microenvironment/*immunology ; }, abstract = {Extracellular vesicles (EVs) are important players of intercellular signalling mechanisms, including communication with and among immune cells. EVs can affect the surrounding tissue as well as peripheral cells. Recently, EVs have been identified to be involved in the aetiology of several diseases, including cancer. Tumour cell-released EVs or exosomes have been shown to promote a tumour-supporting environment in non-malignant tissue and, thus, benefit metastasis. The underlying mechanisms are numerous: loss of antigen expression, direct suppression of immune effector cells, exchange of nucleic acids, alteration of the recipient cells' transcription and direct suppression of immune cells. Consequently, tumour cells can subvert the host's immune detection as well as suppress the immune system. On the contrary, recent studies reported the existence of EVs able to activate immune cells, thus promoting the tumour-directed immune response. In this article, the immunosuppressive capabilities of EVs, on the one hand, and their potential use in immunoactivation and therapeutic potential, on the other hand, are discussed.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158310, year = {2018}, author = {Menard, JA and Cerezo-Magaña, M and Belting, M}, title = {Functional role of extracellular vesicles and lipoproteins in the tumour microenvironment.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158310}, issn = {1471-2970}, mesh = {*Cell Communication ; Extracellular Vesicles/*physiology ; Humans ; Lipoproteins/*physiology ; *Signal Transduction ; Tumor Microenvironment/*physiology ; }, abstract = {Cancer can be regarded as an invasive organ that exhibits unique plasticity provided by coordinated, cancer cell-stromal cell communication in the tumour microenvironment. Typical stress factors in the tumour niche, such as hypoxia and acidosis, are major drivers and modulators of these events. Recent findings reveal an important role of extracellular vesicles and lipoproteins in cancer cell adaption to exogenous stress. Adaptive mechanisms include stimulation of angiogenesis and increased metastasis. Here, we will discuss the similarities and distinct features of these endogenous nanoparticles and their roles as signalosomes and nutrient sources in cancer. We will focus on the accumulating evidence for a central role of cell-surface heparan sulphate proteoglycans in the uptake of extracellular vesicles and lipoproteins.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158309, year = {2018}, author = {Tkach, M and Kowal, J and Théry, C}, title = {Why the need and how to approach the functional diversity of extracellular vesicles.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158309}, issn = {1471-2970}, mesh = {Cell Communication ; Exosomes/physiology ; Extracellular Vesicles/*pathology/*physiology ; Humans ; Tumor Microenvironment/*physiology ; }, abstract = {In the past decade, cell-to-cell communication mediated by exosomes has attracted growing attention from biomedical scientists and physicians, leading to several recent publications in top-tier journals. Exosomes are generally defined as secreted membrane vesicles, or extracellular vesicles (EVs), corresponding to the intraluminal vesicles of late endosomal compartments, which are secreted upon fusion of multi-vesicular endosomes with the cell's plasma membrane. Cells, however, were shown to release other types of EVs, for instance, by direct budding off their plasma membrane. Some of these EVs share with exosomes major biophysical and biochemical characteristics, such as size, density and membrane orientation, which impose difficulties in their efficient separation. Despite frequent claims in the literature, whether exosomes really display more important patho/physiological functions, or are endowed with higher potential as diagnostic or therapeutic tools than other EVs, is not yet convincingly demonstrated. In this opinion article, we describe reasons for this lack of precision knowledge in the current stage of the EV field, we review recently described approaches to overcome these caveats, and we propose ways to improve our knowledge on the respective functions of distinct EVs, which will be crucial for future development of well-designed EV-based clinical applications.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158308, year = {2018}, author = {Oushy, S and Hellwinkel, JE and Wang, M and Nguyen, GJ and Gunaydin, D and Harland, TA and Anchordoquy, TJ and Graner, MW}, title = {Glioblastoma multiforme-derived extracellular vesicles drive normal astrocytes towards a tumour-enhancing phenotype.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158308}, issn = {1471-2970}, mesh = {Astrocytes/*pathology ; Cell Line, Tumor ; Cell Movement ; *Cell Proliferation ; Cytokines/*metabolism ; Extracellular Vesicles/*metabolism ; Glioblastoma/*physiopathology ; Humans ; Phenotype ; *Tumor Microenvironment ; }, abstract = {Glioblastoma multiforme (GBM) is a devastating tumour with abysmal prognoses. We desperately need novel approaches to understand GBM biology and therapeutic vulnerabilities. Extracellular vesicles (EVs) are membrane-enclosed nanospheres released locally and systemically by all cells, including tumours, with tremendous potential for intercellular communication. Tumour EVs manipulate their local environments as well as distal targets; EVs may be a mechanism for tumourigenesis in the recurrent GBM setting. We hypothesized that GBM EVs drive molecular changes in normal human astrocytes (NHAs), yielding phenotypically tumour-promoting, or even tumourigenic, entities. We incubated NHAs with GBM EVs and examined the astrocytes for changes in cell migration, cytokine release and tumour cell growth promotion via the conditioned media. We measured alterations in intracellular signalling and transformation capacity (astrocyte growth in soft agar). GBM EV-treated NHAs displayed increased migratory capacity, along with enhanced cytokine production which promoted tumour cell growth. GBM EV-treated NHAs developed tumour-like signalling patterns and exhibited colony formation in soft agar, reminiscent of tumour cells themselves. GBM EVs modify the local environment to benefit the tumour itself, co-opting neighbouring astrocytes to promote tumour growth, and perhaps even driving astrocytes to a tumourigenic phenotype. Such biological activities could have profound impacts in the recurrent GBM setting.This article is part of the discussion meeting issue 'Extracellular vesicles and the tumour microenvironment'.}, } @article {pmid29158307, year = {2018}, author = {Carter, DRF and Clayton, A and Devitt, A and Hunt, S and Lambert, DW}, title = {Extracellular vesicles in the tumour microenvironment.}, journal = {Philosophical transactions of the Royal Society of London. Series B, Biological sciences}, volume = {373}, number = {1737}, pages = {}, pmid = {29158307}, issn = {1471-2970}, mesh = {Extracellular Vesicles/*physiology ; Neoplasms/*physiopathology ; Tumor Microenvironment/*physiology ; }, } @article {pmid29158161, year = {2018}, author = {Toussaint, A and Van Gijsegem, F}, title = {Extension of the transposable bacterial virus family: two genomic organisations among phages and prophages with a Tn552-related transposase.}, journal = {Research in microbiology}, volume = {169}, number = {9}, pages = {495-499}, doi = {10.1016/j.resmic.2017.11.002}, pmid = {29158161}, issn = {1769-7123}, mesh = {Bacteriophages/classification/enzymology/*genetics ; DNA, Viral/genetics ; *Genome, Viral ; Genomics/methods ; Prophages/classification/*genetics ; Sequence Analysis, DNA ; Transposases/*genetics ; Viral Proteins/genetics ; }, abstract = {Mu-like transposable phages and prophages have been isolated from, or predicted, in a wide range of bacterial phyla. However, related B3-like transposable phages, which differ in their genome organisation and the DDE transposase and transposition activator they code for have thus far been restricted to a very limited set of hosts. Through sequence similarity searches, we have now expanded the number of predicted B3-like prophages and uncovered a third genomic organisation. These new genomes, although only prophages, further illustrate the previously reported mosaicism existing in the proposed "Saltoviridae" family of Caudovirales, and further support the proposal to move morphology criteria (contractile vs. flexible or short tail, i.e. Myo-vs. Sipho- or Podoviridae) from the family to the subfamily level in the taxonomic classification of the Caudovirales.}, } @article {pmid29158032, year = {2018}, author = {Scott, PA and Glenn, TC and Rissler, LJ}, title = {Resolving taxonomic turbulence and uncovering cryptic diversity in the musk turtles (Sternotherus) using robust demographic modeling.}, journal = {Molecular phylogenetics and evolution}, volume = {120}, number = {}, pages = {1-15}, doi = {10.1016/j.ympev.2017.11.008}, pmid = {29158032}, issn = {1095-9513}, mesh = {Animals ; *Biodiversity ; DNA, Mitochondrial/genetics ; Demography ; Genetic Speciation ; Genome ; Geography ; Likelihood Functions ; Models, Biological ; *Phylogeny ; Species Specificity ; Turtles/*anatomy & histology/genetics ; }, abstract = {Accurate and consistent delimitation of species and their relationships provides a necessary framework for comparative studies, understanding evolutionary relationships, and informing conservation management. Despite the ever-increasing availability of genomic data, evolutionary dynamics can still render some relationships exceedingly difficult to resolve, including underlying speciation events that are rapid, recent, or confounded by post-speciation introgression. Here we present an empirical study of musk turtles (Sternotherus), which illustrates approaches to resolve difficult nodes in the Tree of Life that robust species-tree methods fail to resolve. We sequence 4430 RAD-loci from 205 individuals. Independent coalescent-based analyses, corroborated with morphology and geography, strongly support the recognition of cryptic species within Sternotherus, but with conflicting or weak support for some intraspecific relationships. To resolve species-tree conflict, we use a likelihood-based approach to test support for alternative demographic models behind alternative speciation scenarios and argue that demographic model testing has an important role for resolving systematic relationships in recent, rapid radiations. Species-tree and demographic modeling strongly support the elevation of two nominal subspecies in Sternotherus to species and the recognition of a previously cryptic species (S. intermedius sp. nov.) described within. The evolutionary and taxonomic history of Sternotherus is discussed in the context of these new species and novel and well-supported systematic hypotheses.}, } @article {pmid29157967, year = {2018}, author = {Nice, TJ and Robinson, BA and Van Winkle, JA}, title = {The Role of Interferon in Persistent Viral Infection: Insights from Murine Norovirus.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {510-524}, pmid = {29157967}, issn = {1878-4380}, support = {R01 AI130055/AI/NIAID NIH HHS/United States ; }, abstract = {Persistent viral infections result from evasion or avoidance of sterilizing immunity, extend the timeframe of virus transmission, and can trigger disease. Prior studies in mouse models of persistent infection have suggested that ineffective adaptive immune responses are necessary for persistent viral infection. However, recent work in the murine norovirus (MNV) model of persistent infection demonstrates that innate immunity can control both early and persistent viral replication independently of adaptive immune effector functions. Interferons (IFNs) are central to the innate control of persistent MNV, apart from a role in modulating adaptive immunity. Furthermore, subtypes of IFN play distinct tissue-specific roles in innate control of persistent MNV infection. Type I IFN (IFN-α/β) controls systemic replication, and type III IFN (IFN-λ) controls MNV persistence in the intestinal epithelium. In this article, we review recent findings in the MNV model, highlighting the role of IFNs and innate immunity in clearing persistent viral infection, and discussing the broader implications of these findings for control of persistent human infections.}, } @article {pmid29157966, year = {2018}, author = {Ter Kuile, BH and Hoeksema, M}, title = {Antibiotic Killing through Incomplete DNA Repair.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {2-4}, doi = {10.1016/j.tim.2017.11.006}, pmid = {29157966}, issn = {1878-4380}, mesh = {*Anti-Bacterial Agents ; DNA Damage ; *DNA Repair ; Oxidation-Reduction ; Reactive Oxygen Species ; }, abstract = {Two recent studies show that incomplete repair of DNA damage due to oxidized nucleotides is crucial for reactive oxygen species (ROS)-related antimicrobial lethality. Using widely different experimental approaches they both reach the same conclusions on the role of downstream ROS production in cell killing upon exposure to bactericidal antimicrobials.}, } @article {pmid29157563, year = {2018}, author = {Duong, TB and Ravisankar, P and Song, YC and Gafranek, JT and Rydeen, AB and Dohn, TE and Barske, LA and Crump, JG and Waxman, JS}, title = {Nr2f1a balances atrial chamber and atrioventricular canal size via BMP signaling-independent and -dependent mechanisms.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {7-14}, pmid = {29157563}, issn = {1095-564X}, support = {R01 DE018405/DE/NIDCR NIH HHS/United States ; R01 HL112893/HL/NHLBI NIH HHS/United States ; T32 HL007381/HL/NHLBI NIH HHS/United States ; R35 DE027550/DE/NIDCR NIH HHS/United States ; R01 HL137766/HL/NHLBI NIH HHS/United States ; K99 DE026239/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Bone Morphogenetic Proteins/genetics/*metabolism ; DNA-Binding Proteins/genetics/*metabolism ; Heart Atria/embryology/pathology ; Heart Septal Defects, Atrial/*embryology/genetics/pathology ; Humans ; Myocytes, Cardiac/*metabolism/pathology ; *Signal Transduction ; Transcription Factors/genetics/*metabolism ; Zebrafish/*embryology/genetics ; Zebrafish Proteins/genetics/*metabolism ; }, abstract = {Determination of appropriate chamber size is critical for normal vertebrate heart development. Although Nr2f transcription factors promote atrial maintenance and differentiation, how they determine atrial size remains unclear. Here, we demonstrate that zebrafish Nr2f1a is expressed in differentiating atrial cardiomyocytes. Zebrafish nr2f1a mutants have smaller atria due to a specific reduction in atrial cardiomyocyte (AC) number, suggesting it has similar requirements to Nr2f2 in mammals. Furthermore, the smaller atria in nr2f1a mutants are derived from distinct mechanisms that perturb AC differentiation at the chamber poles. At the venous pole, Nr2f1a enhances the rate of AC differentiation. Nr2f1a also establishes the atrial-atrioventricular canal (AVC) border through promoting the differentiation of mature ACs. Without Nr2f1a, AVC markers are expanded into the atrium, resulting in enlarged endocardial cushions (ECs). Inhibition of Bmp signaling can restore EC development, but not AC number, suggesting that Nr2f1a concomitantly coordinates atrial and AVC size through both Bmp-dependent and independent mechanisms. These findings provide insight into conserved functions of Nr2f proteins and the etiology of atrioventricular septal defects (AVSDs) associated with NR2F2 mutations in humans.}, } @article {pmid29157562, year = {2018}, author = {Tomer, D and Chippalkatti, R and Mitra, K and Rikhy, R}, title = {ERK regulates mitochondrial membrane potential in fission deficient Drosophila follicle cells during differentiation.}, journal = {Developmental biology}, volume = {434}, number = {1}, pages = {48-62}, doi = {10.1016/j.ydbio.2017.11.009}, pmid = {29157562}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation/*physiology ; Cytoskeletal Proteins/genetics/metabolism ; Drosophila Proteins/genetics/metabolism ; Drosophila melanogaster ; Extracellular Signal-Regulated MAP Kinases/genetics/metabolism ; Female ; GTP-Binding Proteins/genetics/metabolism ; MAP Kinase Signaling System/*physiology ; Membrane Potential, Mitochondrial/*physiology ; Mitochondrial Dynamics/*physiology ; Oogenesis/*physiology ; Ovarian Follicle/cytology/*metabolism ; Receptors, Notch/genetics/metabolism ; }, abstract = {Mitochondrial morphology regulatory proteins interact with signaling pathways involved in differentiation. In Drosophila oogenesis, EGFR signaling regulates mitochondrial fragmentation in posterior follicle cells (PFCs). EGFR driven oocyte patterning and Notch signaling mediated differentiation are abrogated when PFCs are deficient for the mitochondrial fission protein Drp1. It is not known whether fused mitochondrial morphology in drp1 mutant PFCs exerts its effects on these signaling pathways through a change in mitochondrial electron transport chain (ETC) activity. In this study we show that aggregated mitochondria in drp1 mutant PFCs have increased mitochondrial membrane potential. We perform experiments to assess the signaling pathway regulating mitochondrial membrane potential and how this impacts follicle cell differentiation. We find that drp1 mutant PFCs show increase in phosphorylated ERK (dpERK) formed downstream of EGFR signaling. ERK regulates high mitochondrial membrane potential in drp1 mutant PFCs. PFCs depleted of ERK and drp1 are able to undergo Notch mediated differentiation. Notably mitochondrial membrane potential decrease via ETC inhibition activates Notch signaling at an earlier stage in wild type and suppresses the Notch signaling defect in drp1 mutant PFCs. Thus, this study shows that the EGFR pathway maintains mitochondrial morphology and mitochondrial membrane potential in follicle cells for its functioning and decrease in mitochondrial membrane potential is needed for Notch mediated differentiation.}, } @article {pmid29156444, year = {2018}, author = {DasSarma, P and DasSarma, S}, title = {Survival of microbes in Earth's stratosphere.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {24-30}, doi = {10.1016/j.mib.2017.11.002}, pmid = {29156444}, issn = {1879-0364}, mesh = {*Atmosphere ; Bacteria/*metabolism/radiation effects ; Climate Change ; Cold Temperature ; *Earth (Planet) ; Exobiology ; Fungi/radiation effects ; *Microbial Viability ; Ozone ; Ultraviolet Rays ; }, abstract = {The remarkable survival of microorganisms high above the surface of the Earth is of increasing interest. At stratospheric levels, multiple stressors including ultraviolet and ionizing radiation, low temperatures, hypobaric conditions, extreme desiccation, and nutrient scarcity are all significant challenges. Our understanding of which microorganisms are capable of tolerating such stressful conditions has been addressed by stratospheric sample collection and survival assays, through launching and recovery, and exposure to simulated conditions in the laboratory. Here, we review stratospheric microbiology studies providing our current perspective on microbial life at extremely high altitudes and discuss implications for health and agriculture, climate change, planetary protection, and astrobiology.}, } @article {pmid29156371, year = {2018}, author = {Bomar, L and Brugger, SD and Lemon, KP}, title = {Bacterial microbiota of the nasal passages across the span of human life.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {8-14}, pmid = {29156371}, issn = {1879-0364}, support = {R01 GM117174/GM/NIGMS NIH HHS/United States ; }, mesh = {Adolescent ; Age Factors ; Aged ; Bacteria/classification/genetics/*isolation & purification ; Bacterial Infections/microbiology ; Child, Preschool ; DNA, Bacterial ; Disease Susceptibility/etiology/immunology ; Female ; Humans ; Infant ; Infant, Newborn ; *Microbiota ; Middle Aged ; Nasal Cavity/*microbiology ; RNA, Ribosomal, 16S ; Respiratory Tract Infections/*microbiology ; }, abstract = {The human nasal passages host major human pathogens. Recent research suggests that the microbial communities inhabiting the epithelial surfaces of the nasal passages are a key factor in maintaining a healthy microenvironment by affecting both resistance to pathogens and immunological responses. The nasal bacterial microbiota shows distinct changes over the span of human life and disruption by environmental factors might be associated with both short- and long-term health consequences, such as susceptibility to viral and bacterial infections and disturbances of the immunological balance. Because infants and older adults experience a high burden of morbidity and mortality from respiratory tract infections, we review recent data on the bacterial nasal microbiota composition in health and acute respiratory infection in these age groups.}, } @article {pmid29156096, year = {2018}, author = {Joseph, PN and Emberts, Z and Sasson, DA and Miller, CW}, title = {Males that drop a sexually selected weapon grow larger testes.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {113-122}, doi = {10.1111/evo.13387}, pmid = {29156096}, issn = {1558-5646}, abstract = {Costly sexually selected weapons are predicted to trade off with postcopulatory traits, such as testes. Although weapons can be important for achieving access to females, individuals of some species can permanently drop (i.e. autotomize) their weapons, without regeneration, to escape danger. We capitalized on this natural behavior to experimentally address whether the loss of a sexually selected weapon leads to increased testes investment in the leaf-footed cactus bug, Narnia femorata Stål (Hemiptera: Coreidae). In a second experiment, we measured offspring production for males that lost a weapon during development. As predicted, males that dropped a hind limb during development grew significantly larger testes than the control treatments. Hind-limb autotomy did not result in the enlargement of other nearby traits. Our results are the first to experimentally demonstrate that males compensate for natural weapon loss by investing more in testes. In a second experiment we found that females paired with males that lost a hind limb had 40% lower egg hatching success than females paired with intact males, perhaps because of lower mating receptivity to males with a lost limb. Importantly, in those cases where viable offspring were produced, males missing a hind limb produced 42% more offspring than males with intact limbs. These results suggest that the loss of a hind-limb weapon can, in some cases, lead to greater fertilization success.}, } @article {pmid29155044, year = {2018}, author = {Shen, Q and Toulabi, LB and Shi, H and Nicklow, EE and Liu, J}, title = {The forkhead transcription factor UNC-130/FOXD integrates both BMP and Notch signaling to regulate dorsoventral patterning of the C. elegans postembryonic mesoderm.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {75-83}, pmid = {29155044}, issn = {1095-564X}, support = {R01 GM066953/GM/NIGMS NIH HHS/United States ; R01 GM103869/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Body Patterning ; Bone Morphogenetic Proteins/*metabolism ; Caenorhabditis elegans/genetics ; Caenorhabditis elegans Proteins/genetics/*metabolism ; Cell Differentiation ; Cell Lineage/genetics/physiology ; Embryo, Nonmammalian/metabolism ; Forkhead Transcription Factors/metabolism ; Gene Expression Regulation, Developmental/genetics ; Mesoderm/*metabolism ; Receptors, Notch/metabolism ; Signal Transduction ; Transcription Factors/genetics/*metabolism ; Zinc Fingers ; }, abstract = {The proper development of a multicellular organism requires precise spatial and temporal coordination of cell intrinsic and cell extrinsic regulatory mechanisms. Both Notch signaling and bone morphogenetic protein (BMP) signaling function to regulate the proper development of the C. elegans postembryonic mesoderm. We have identified the C. elegans FOXD transcription factor UNC-130 as a major target functioning downstream of both BMP signaling and Notch signaling to regulate dorsoventral patterning of the postembryonic mesoderm. We showed that unc-130 expression in the postembryonic M lineage is asymmetric: its absence of expression in the dorsal side of the M lineage requires the antagonism of BMP signaling by the zinc finger transcription factor SMA-9, while its expression in the ventral side of the M lineage is activated by LIN-12/Notch signaling. We further showed that the regulation of UNC-130 expression by BMP signaling and Notch signaling is specific to the M lineage, as the ventral expression of UNC-130 in the embryonically-derived bodywall muscles was not affected in either BMP pathway or Notch pathway mutants. Finally, we showed that the function of UNC-130 in the M lineage is independent of UNC-129, a gene previously shown to function downstream of and be repressed by UNC-130 for axon guidance. Our studies uncovered a new function of UNC-130/FOXD in the C. elegans postembryonic mesoderm, and identify UNC-130 as a critical factor that integrates two independent spatial cues for the proper patterning and fate specification of the C. elegans postembryonic mesoderm.}, } @article {pmid29155043, year = {2018}, author = {Martins, LR and Bung, RK and Koch, S and Richter, K and Schwarzmüller, L and Terhardt, D and Kurtulmus, B and Niehrs, C and Rouhi, A and Lohmann, I and Pereira, G and Fröhling, S and Glimm, H and Scholl, C}, title = {Stk33 is required for spermatid differentiation and male fertility in mice.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {84-93}, doi = {10.1016/j.ydbio.2017.11.007}, pmid = {29155043}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation/physiology ; Fertility/physiology ; Male ; Mice ; Mice, Knockout ; Microtubules/metabolism ; Protein-Serine-Threonine Kinases/genetics/*metabolism ; Spermatids/*enzymology ; Spermatocytes/cytology/enzymology ; Spermatogenesis/physiology ; Spermatozoa/enzymology ; Testis/enzymology ; }, abstract = {Spermiogenesis is the final phase during sperm cell development in which round spermatids undergo dramatic morphological changes to generate spermatozoa. Here we report that the serine/threonine kinase Stk33 is essential for the differentiation of round spermatids into functional sperm cells and male fertility. Constitutive Stk33 deletion in mice results in severely malformed and immotile spermatozoa that are particularly characterized by disordered structural tail elements. Stk33 expression first appears in primary spermatocytes, and targeted deletion of Stk33 in these cells recapitulates the defects observed in constitutive knockout mice, confirming a germ cell-intrinsic function. Stk33 protein resides in the cytoplasm and partially co-localizes with the caudal end of the manchette, a transient structure that guides tail elongation, in elongating spermatids, and loss of Stk33 leads to the appearance of a tight, straight and elongated manchette. Together, these results identify Stk33 as an essential regulator of spermatid differentiation and male fertility.}, } @article {pmid29154454, year = {2018}, author = {Jin, ZB and Li, Z and Liu, Z and Jiang, Y and Cai, XB and Wu, J}, title = {Identification of de novo germline mutations and causal genes for sporadic diseases using trio-based whole-exome/genome sequencing.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1014-1031}, doi = {10.1111/brv.12383}, pmid = {29154454}, issn = {1469-185X}, abstract = {Whole-genome or whole-exome sequencing (WGS/WES) of the affected proband together with normal parents (trio) is commonly adopted to identify de novo germline mutations (DNMs) underlying sporadic cases of various genetic disorders. However, our current knowledge of the occurrence and functional effects of DNMs remains limited and accurately identifying the disease-causing DNM from a group of irrelevant DNMs is complicated. Herein, we provide a general-purpose discussion of important issues related to pathogenic gene identification based on trio-based WGS/WES data. Specifically, the relevance of DNMs to human sporadic diseases, current knowledge of DNM biogenesis mechanisms, and common strategies or software tools used for DNM detection are reviewed, followed by a discussion of pathogenic gene prioritization. In addition, several key factors that may affect DNM identification accuracy and causal gene prioritization are reviewed. Based on recent major advances, this review both sheds light on how trio-based WGS/WES technologies can play a significant role in the identification of DNMs and causal genes for sporadic diseases, and also discusses existing challenges.}, } @article {pmid29154077, year = {2018}, author = {Litsios, A and Ortega, ÁD and Wit, EC and Heinemann, M}, title = {Metabolic-flux dependent regulation of microbial physiology.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {71-78}, doi = {10.1016/j.mib.2017.10.029}, pmid = {29154077}, issn = {1879-0364}, mesh = {Cell Physiological Phenomena ; Escherichia coli/*physiology ; Metabolic Flux Analysis ; Metabolic Networks and Pathways/*genetics/physiology ; Models, Biological ; Protein Biosynthesis ; }, abstract = {According to the most prevalent notion, changes in cellular physiology primarily occur in response to altered environmental conditions. Yet, recent studies have shown that changes in metabolic fluxes can also trigger phenotypic changes even when environmental conditions are unchanged. This suggests that cells have mechanisms in place to assess the magnitude of metabolic fluxes, that is, the rate of metabolic reactions, and use this information to regulate their physiology. In this review, we describe recent evidence for metabolic flux-sensing and flux-dependent regulation. Furthermore, we discuss how such sensing and regulation can be mechanistically achieved and present a set of new candidates for flux-signaling metabolites. Similar to metabolic-flux sensing, we argue that cells can also sense protein translation flux. Finally, we elaborate on the advantages that flux-based regulation can confer to cells.}, } @article {pmid29153587, year = {2018}, author = {Armistead, JS and Adams, JH}, title = {Advancing Research Models and Technologies to Overcome Biological Barriers to Plasmodium vivax Control.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {114-126}, doi = {10.1016/j.pt.2017.10.009}, pmid = {29153587}, issn = {1471-5007}, support = {R01 AI064478/AI/NIAID NIH HHS/United States ; }, mesh = {Humans ; Malaria, Vivax/*prevention & control ; Plasmodium vivax/*physiology ; Research/*trends ; }, abstract = {Malaria prevalence has declined in the past 10 years, especially outside of sub-Saharan Africa. However, the proportion of cases due to Plasmodium vivax is increasing, accounting for up to 90-100% of the malaria burden in endemic regions. Nonetheless, investments in malaria research and control still prioritize Plasmodium falciparum while largely neglecting P. vivax. Specific biological features of P. vivax, particularly invasion of reticulocytes, occurrence of dormant liver forms of the parasite, and the potential for transmission of sexual-stage parasites prior to onset of clinical illness, promote its persistence and hinder development of research tools and interventions. This review discusses recent advances in P. vivax research, current knowledge of its unique biology, and proposes priorities for P. vivax research and control efforts.}, } @article {pmid29153333, year = {2018}, author = {de la Torre, I and Albert, RM and Arroyo, A and Macphail, R and McHenry, LJ and Mora, R and Njau, JK and Pante, MC and Rivera-Rondón, CA and Rodríguez-Cintas, Á and Stanistreet, IG and Stollhofen, H and Wehr, K}, title = {New excavations at the HWK EE site: Archaeology, paleoenvironment and site formation processes during late Oldowan times at Olduvai Gorge, Tanzania.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {140-202}, doi = {10.1016/j.jhevol.2017.07.018}, pmid = {29153333}, issn = {1095-8606}, abstract = {This paper reports the results of renewed fieldwork at the HWK EE site (Olduvai Gorge, Tanzania). HWK EE is positioned across the boundary between Lower and Middle Bed II, a crucial interval for studying the emergence of the Acheulean at Olduvai Gorge. Our excavations at HWK EE have produced one of the largest collections of fossils and artefacts from any Oldowan site, distributed across several archaeological units and a large excavation surface in four separate trenches that can be stratigraphically correlated. Here we present the main stratigraphic and archaeological units and discuss site formation processes. Results show a great density of fossils and stone tools vertically through two stratigraphic intervals (Lemuta and Lower Augitic Sandstone) and laterally across an area of around 300 m2, and highlight the confluence of biotic and abiotic agents in the formation of the assemblage. The large size and diversity of the assemblage, as well as its good preservation, qualify HWK EE as a reference site for the study of the late Oldowan at Olduvai Gorge and elsewhere in Africa. In addition, the description of the stratigraphic and archaeological sequence of HWK EE presented in this paper constitutes the foundation for further studies on hominin behavior and paleoecology in Lower and Middle Bed II.}, } @article {pmid29153263, year = {2018}, author = {}, title = {Simona Stäger: Sabotaging a Master Manipulator.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {91-92}, doi = {10.1016/j.pt.2017.10.011}, pmid = {29153263}, issn = {1471-5007}, mesh = {B-Lymphocytes/parasitology ; Canada ; Host-Parasite Interactions/*immunology ; Humans ; *Leishmania ; Leishmaniasis/*immunology/*prevention & control ; World Health Organization ; }, } @article {pmid29153262, year = {2018}, author = {Ishtiaq, F}, title = {A Call to Introduce Structured Zika Surveillance in India.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {92-95}, doi = {10.1016/j.pt.2017.10.008}, pmid = {29153262}, issn = {1471-5007}, support = {IA/S/12/2/500629//Wellcome Trust-DBT India Alliance/India ; IA/I(S)/12/2/500629//Wellcome Trust-DBT India Alliance/India ; }, mesh = {Disease Outbreaks/*prevention & control ; Humans ; India ; *Population Surveillance ; Public Health/trends ; Risk Management ; Zika Virus ; Zika Virus Infection/diagnosis/*prevention & control ; }, abstract = {India has the climatic conditions conducive to year-round transmission of Zika virus, and a structured disease surveillance program should be implemented to prevent an outbreak. Such a program should (i) start screening before an outbreak arises; (ii) collect baseline data to assess future disease risk and monitor potential birth defects; and (iii) provide new insights into the ecology of the disease and inform public health policy following the one health concept.}, } @article {pmid29152676, year = {2018}, author = {Yoon, J and Yasumoto-Hirose, M and Kasai, H}, title = {Coraliitalea coralii gen. nov., sp. nov., a Marine Bacterium of the Family Flavobacteriaceae Isolated from the Hard Coral Galaxea fascicularis.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {464-470}, pmid = {29152676}, issn = {1432-0991}, mesh = {Animals ; Anthozoa/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry/metabolism ; Flavobacteriaceae/classification/genetics/*isolation & purification/metabolism ; Japan ; Phylogeny ; Seawater/microbiology ; }, abstract = {A polyphasic taxonomic study was performed on a novel strain designated as 04OKA-3-121T, which was isolated from the hard coral Galaxea fascicularis L. collected at Akajima, Okinawa, Japan. These bacterial cells were observed to be pale-yellow, Gram-stain-negative, strictly aerobic, chemoheterotrophic, non-spore forming, non-motile, and rod-shaped. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that the novel marine isolate is affiliated with the family Flavobacteriaceae of the phylum Bacteroidetes and that it shared the highest (93.6%) sequence similarity with Pseudozobellia thermophila KMM 3531T. The strain could be phenotypically differentiated from related members of the family Flavobacteriaceae. Major fatty acids of strain 04OKA-3-121T were iso-C15:0, iso-C15:1 G, and C16:1 ω7c and/or C16:1 ω6c. The DNA G + C content of the strain was determined to be 38.8 mol% and the major respiratory quinone was identified as menaquinone 6 (MK-6). Strain 04OKA-3-121T had phosphatidylethanolamine, two unidentified aminolipids, and eight unidentified lipids as polar lipids. From the distinct phylogenetic position and combination of genotypic and phenotypic characteristics, the strain is considered to represent a novel genus in the family Flavobacteriaceae, for which the name Coraliitalea coralii gen. nov., sp. nov. is proposed. The type strain of C. coralii gen. nov., sp. nov. is 04OKA-3-121T (= KCTC 52378T = NBRC 112329T).}, } @article {pmid29151601, year = {2018}, author = {Du Toit, A}, title = {Antimicrobials: Daylight robbery by Acinetobacter.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {2-3}, pmid = {29151601}, issn = {1740-1534}, } @article {pmid29151589, year = {2018}, author = {Wrighton, KH}, title = {Transcription: Shedding light on alternative promoter selection.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {4-5}, pmid = {29151589}, issn = {1471-0064}, } @article {pmid29151588, year = {2018}, author = {Hindorff, LA and Bonham, VL and Brody, LC and Ginoza, MEC and Hutter, CM and Manolio, TA and Green, ED}, title = {Prioritizing diversity in human genomics research.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {175-185}, pmid = {29151588}, issn = {1471-0064}, abstract = {Recent studies have highlighted the imperatives of including diverse and under-represented individuals in human genomics research and the striking gaps in attaining that inclusion. With its multidecade experience in supporting research and policy efforts in human genomics, the National Human Genome Research Institute is committed to establishing foundational approaches to study the role of genomic variation in health and disease that include diverse populations. Large-scale efforts to understand biology and health have yielded key scientific findings, lessons and recommendations on how to increase diversity in genomic research studies and the genomic research workforce. Increased attention to diversity will increase the accuracy, utility and acceptability of using genomic information for clinical care.}, } @article {pmid29150984, year = {2018}, author = {Goutte, S and Dubois, A and Howard, SD and Márquez, R and Rowley, JJL and Dehling, JM and Grandcolas, P and Xiong, RC and Legendre, F}, title = {How the environment shapes animal signals: a test of the acoustic adaptation hypothesis in frogs.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {148-158}, doi = {10.1111/jeb.13210}, pmid = {29150984}, issn = {1420-9101}, mesh = {Adaptation, Physiological/*physiology ; Animals ; Anura/classification/*physiology ; *Environment ; Phylogeny ; Vocalization, Animal/*physiology ; }, abstract = {Long-distance acoustic signals are widely used in animal communication systems and, in many cases, are essential for reproduction. The acoustic adaptation hypothesis (AAH) implies that acoustic signals should be selected for further transmission and better content integrity under the acoustic constraints of the habitat in which they are produced. In this study, we test predictions derived from the AAH in frogs. Specifically, we focus on the difference between torrent frogs and frogs calling in less noisy habitats. Torrents produce sounds that can mask frog vocalizations and constitute a major acoustic constraint on call evolution. We combine data collected in the field, material from scientific collections and the literature for a total of 79 primarily Asian species, of the families Ranidae, Rhacophoridae, Dicroglossidae and Microhylidae. Using phylogenetic comparative methods and including morphological and environmental potential confounding factors, we investigate putatively adaptive call features in torrent frogs. We use broad habitat categories as well as fine-scale habitat measurements and test their correlation with six call characteristics. We find mixed support for the AAH. Spectral features of torrent frog calls are different from those of frogs calling in other habitats and are related to ambient noise levels, as predicted by the AAH. However, temporal call features do not seem to be shaped by the frogs' calling habitats. Our results underline both the complexity of call evolution and the need to consider multiple factors when investigating this issue.}, } @article {pmid29150962, year = {2018}, author = {Kutzer, MAM and Kurtz, J and Armitage, SAO}, title = {Genotype and diet affect resistance, survival, and fecundity but not fecundity tolerance.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {159-171}, doi = {10.1111/jeb.13211}, pmid = {29150962}, issn = {1420-9101}, mesh = {Animals ; *Diet ; Disease Resistance/genetics ; Drosophila melanogaster/genetics/microbiology/*physiology ; Female ; Fertility/genetics/physiology ; Host-Pathogen Interactions/genetics/*physiology ; Lactococcus lactis/physiology ; Pseudomonas/physiology ; Survival Analysis ; }, abstract = {Insects are exposed to a variety of potential pathogens in their environment, many of which can severely impact fitness and health. Consequently, hosts have evolved resistance and tolerance strategies to suppress or cope with infections. Hosts utilizing resistance improve fitness by clearing or reducing pathogen loads, and hosts utilizing tolerance reduce harmful fitness effects per pathogen load. To understand variation in, and selective pressures on, resistance and tolerance, we asked to what degree they are shaped by host genetic background, whether plasticity in these responses depends upon dietary environment, and whether there are interactions between these two factors. Females from ten wild-type Drosophila melanogaster genotypes were kept on high- or low-protein (yeast) diets and infected with one of two opportunistic bacterial pathogens, Lactococcus lactis or Pseudomonas entomophila. We measured host resistance as the inverse of bacterial load in the early infection phase. The relationship (slope) between fly fecundity and individual-level bacteria load provided our fecundity tolerance measure. Genotype and dietary yeast determined host fecundity and strongly affected survival after infection with pathogenic P. entomophila. There was considerable genetic variation in host resistance, a commonly found phenomenon resulting from for example varying resistance costs or frequency-dependent selection. Despite this variation and the reproductive cost of higher P. entomophila loads, fecundity tolerance did not vary across genotypes. The absence of genetic variation in tolerance may suggest that at this early infection stage, fecundity tolerance is fixed or that any evolved tolerance mechanisms are not expressed under these infection conditions.}, } @article {pmid29150703, year = {2018}, author = {Zhang, M and Ge, J and Yu, X}, title = {Transcriptome Analysis Reveals the Mechanism of Fungicidal of Thymol Against Fusarium oxysporum f. sp. niveum.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {410-419}, doi = {10.1007/s00284-017-1396-6}, pmid = {29150703}, issn = {1432-0991}, support = {31401779//National Natural Science Foundation of China/ ; BK20140745//Natural Science Foundation of Jiangsu Province/ ; cx(15)1035//ndependent Innovation Fund of Agricultural Sciences in Jiangsu Province of China/ ; }, mesh = {Citrullus/microbiology ; Fungal Proteins/genetics/metabolism ; Fungicides, Industrial/*pharmacology ; Fusarium/*drug effects/*genetics/metabolism ; Gene Expression Profiling ; Plant Diseases/*microbiology ; Thymol/*pharmacology ; }, abstract = {Fusarium oxysporum: f. sp. niveum (Fusarium oxysporum) causes watermelon wilt, drastically reducing its yield. Thymol (5-methyl-2-(1-methylethyl) phenol, PubChem CID: 6989) has been extensively reported to have antimicrobial activity against pathogenic microorganisms. In this study, the growth of F. oxysporum was significantly inhibited by thymol in vitro. The dry weight of F. oxysporum was decreased significantly. Thymol-induced cell membrane damage was observed at 24 hpi (hours post-incubation). Therefore, the changes in the gene expression level of F. oxysporum after treatment with 80 μg/mL (average EC50 value) of thymol were analyzed using RNA-Seq to reveal the underlying fungicidal mechanisms of thymol. Among the 5057 differentially expressed genes (DEGs), 2440 and 2617 were up-regulated and down-regulated, respectively. Bioinformatics analysis demonstrated that the expression levels of most genes, including glycosphingolipid biosynthesis and sphingolipid metabolism, were down-regulated. However, the genes involved in antioxidant activity, chitin biosynthesis, and cell wall modification were up-regulated. These results were verified by quantitative reverse transcription PCR (qRT-PCR). According to these results, thymol produces reactive oxygen species (ROS) accumulation and destroys the integrity of the cell wall and cell membrane by inhibiting the genes involved in cell wall and cell membrane synthesis.}, } @article {pmid29150386, year = {2018}, author = {Eleftherianos, I and Yadav, S and Kenney, E and Cooper, D and Ozakman, Y and Patrnogic, J}, title = {Role of Endosymbionts in Insect-Parasitic Nematode Interactions.}, journal = {Trends in parasitology}, volume = {34}, number = {5}, pages = {430-444}, doi = {10.1016/j.pt.2017.10.004}, pmid = {29150386}, issn = {1471-5007}, mesh = {Animals ; Host-Parasite Interactions/*physiology ; Insecta/immunology/*parasitology ; Nematoda/*physiology ; *Symbiosis ; }, abstract = {Endosymbiotic bacteria exist in many animals where they develop relationships that affect certain physiological processes in the host. Insects and their nematode parasites form great models for understanding the genetic and molecular basis of immune and parasitic processes. Both organisms contain endosymbionts that possess the ability to interfere with certain mechanisms of immune function and pathogenicity. This review summarizes recent information on the involvement of insect endosymbionts in the response to parasitic nematode infections, and the influence of nematode endosymbionts on specific aspects of the insect immune system. Analyzing this information will be particularly useful for devising endosymbiont-based strategies to intervene in insect immunity or nematode parasitism for the efficient management of noxious insects in the field.}, } @article {pmid29150186, year = {2018}, author = {Perry, JMG and Cooke, SB and Runestad Connour, JA and Burgess, ML and Ruff, CB}, title = {Articular scaling and body mass estimation in platyrrhines and catarrhines: Modern variation and application to fossil anthropoids.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {20-35}, doi = {10.1016/j.jhevol.2017.10.008}, pmid = {29150186}, issn = {1095-8606}, abstract = {Body mass is an important component of any paleobiological reconstruction. Reliable skeletal dimensions for making estimates are desirable but extant primate reference samples with known body masses are rare. We estimated body mass in a sample of extinct platyrrhines and Fayum anthropoids based on four measurements of the articular surfaces of the humerus and femur. Estimates were based on a large extant reference sample of wild-collected individuals with associated body masses, including previously published and new data from extant platyrrhines, cercopithecoids, and hominoids. In general, scaling of joint dimensions is positively allometric relative to expectations of geometric isometry, but negatively allometric relative to expectations of maintaining equivalent joint surface areas. Body mass prediction equations based on articular breadths are reasonably precise, with %SEEs of 17-25%. The breadth of the distal femoral articulation yields the most reliable estimates of body mass because it scales similarly in all major anthropoid taxa. Other joints scale differently in different taxa; therefore, locomotor style and phylogenetic affinity must be considered when calculating body mass estimates from the proximal femur, proximal humerus, and distal humerus. The body mass prediction equations were applied to 36 Old World and New World fossil anthropoid specimens representing 11 taxa, plus two Haitian specimens of uncertain taxonomic affinity. Among the extinct platyrrhines studied, only Cebupithecia is similar to large, extant platyrrhines in having large humeral (especially distal) joints. Our body mass estimates differ from each other and from published estimates based on teeth in ways that reflect known differences in relative sizes of the joints and teeth. We prefer body mass estimators that are biomechanically linked to weight-bearing, and especially those that are relatively insensitive to differences in locomotor style and phylogenetic history. Whenever possible, extant reference samples should be chosen to match target fossils in joint proportionality.}, } @article {pmid29150081, year = {2018}, author = {Ghequire, MGK and De Mot, R}, title = {Turning Over a New Leaf: Bacteriocins Going Green.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {1-2}, doi = {10.1016/j.tim.2017.11.001}, pmid = {29150081}, issn = {1878-4380}, mesh = {Anti-Bacterial Agents/metabolism/pharmacology ; Bacteriocins/classification/genetics/*metabolism/pharmacology ; Colicins/metabolism ; Gram-Negative Bacteria/drug effects ; Plant Leaves/genetics/*metabolism ; Plants/genetics/*metabolism ; Protein Engineering ; Pyocins/metabolism ; Recombinant Proteins/biosynthesis ; }, abstract = {Bacteriocins are potent antibacterial proteins that selectively kill phylogenetic relatives of the producer. Their polymorphic nature, most prominent in γ-Proteobacteria, offers potential for the design of customized bacteriocin cocktails targeting Gram-negative pathogens. As an alternative to recombinant production in bacteria, they are eligible for large-scale production in plants.}, } @article {pmid29149300, year = {2018}, author = {Cherlin, S and Heaps, SE and Nye, TMW and Boys, RJ and Williams, TA and Embley, TM}, title = {The Effect of Nonreversibility on Inferring Rooted Phylogenies.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {984-1002}, pmid = {29149300}, issn = {1537-1719}, support = {//Wellcome Trust/United Kingdom ; 268701//European Research Council/International ; }, abstract = {Most phylogenetic models assume that the evolutionary process is stationary and reversible. In addition to being biologically improbable, these assumptions also impair inference by generating models under which the likelihood does not depend on the position of the root. Consequently, the root of the tree cannot be inferred as part of the analysis. Yet identifying the root position is a key component of phylogenetic inference because it provides a point of reference for polarizing ancestor-descendant relationships and therefore interpreting the tree. In this paper, we investigate the effect of relaxing the unrealistic reversibility assumption and allowing the position of the root to be another unknown. We propose two hierarchical models that are centered on a reversible model but perturbed to allow nonreversibility. The models differ in the degree of structure imposed on the perturbations. The analysis is performed in the Bayesian framework using Markov chain Monte Carlo methods for which software is provided. We illustrate the performance of the two nonreversible models in analyses of simulated data using two types of topological priors. We then apply the models to a real biological data set, the radiation of polyploid yeasts, for which there is robust biological opinion about the root position. Finally, we apply the models to a second biological alignment for which the rooted tree is controversial: the ribosomal tree of life. We compare the two nonreversible models and conclude that both are useful in inferring the position of the root from real biological data.}, } @article {pmid29149249, year = {2018}, author = {Levchenko, A and Kanapin, A and Samsonova, A and Gainetdinov, RR}, title = {Human Accelerated Regions and Other Human-Specific Sequence Variations in the Context of Evolution and Their Relevance for Brain Development.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {166-188}, pmid = {29149249}, issn = {1759-6653}, mesh = {Animals ; Base Sequence ; Brain/growth & development/metabolism ; *Evolution, Molecular ; *Genetic Variation ; *Genome, Human ; Humans ; Regulatory Sequences, Nucleic Acid ; }, abstract = {The review discusses, in a format of a timeline, the studies of different types of genetic variants, present in Homo sapiens, but absent in all other primate, mammalian, or vertebrate species, tested so far. The main characteristic of these variants is that they are found in regions of high evolutionary conservation. These sequence variations include single nucleotide substitutions (called human accelerated regions), deletions, and segmental duplications. The rationale for finding such variations in the human genome is that they could be responsible for traits, specific to our species, of which the human brain is the most remarkable. As became obvious, the vast majority of human-specific single nucleotide substitutions are found in noncoding, likely regulatory regions. A number of genes, associated with these human-specific alleles, often through novel enhancer activity, were in fact shown to be implicated in human-specific development of certain brain areas, including the prefrontal cortex. Human-specific deletions may remove regulatory sequences, such as enhancers. Segmental duplications, because of their large size, create new coding sequences, like new functional paralogs. Further functional study of these variants will shed light on evolution of our species, as well as on the etiology of neurodevelopmental disorders.}, } @article {pmid29148573, year = {2018}, author = {Boulton, K and Walling, CA and Grimmer, AJ and Rosenthal, GG and Wilson, AJ}, title = {Phenotypic and genetic integration of personality and growth under competition in the sheepshead swordtail, Xiphophorus birchmanni.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {187-201}, pmid = {29148573}, issn = {1558-5646}, support = {BB/G022976/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Competition for resources including food, physical space, and potential mates is a fundamental ecological process shaping variation in individual phenotype and fitness. The evolution of competitive ability, in particular social dominance, depends on genetic (co)variation among traits causal (e.g., behavior) or consequent (e.g., growth) to competitive outcomes. If dominance is heritable, it will generate both direct and indirect genetic effects (IGE) on resource-dependent traits. The latter are expected to impose evolutionary constraint because winners necessarily gain resources at the expense of losers. We varied competition in a population of sheepshead swordtails, Xiphophorus birchmanni, to investigate effects on behavior, size, growth, and survival. We then applied quantitative genetic analyses to determine (i) whether competition leads to phenotypic and/or genetic integration of behavior with life history and (ii) the potential for IGE to constrain life history evolution. Size, growth, and survival were reduced at high competition. Male dominance was repeatable and dominant individuals show higher growth and survival. Additive genetic contributions to phenotypic covariance were significant, with the G matrix largely recapitulating phenotypic relationships. Social dominance has a low but significant heritability and is strongly genetically correlated with size and growth. Assuming causal dependence of growth on dominance, hidden IGE will therefore reduce evolutionary potential.}, } @article {pmid29148367, year = {2018}, author = {Carro, L and Veyisoglu, A and Riesco, R and Spröer, C and Klenk, HP and Sahin, N and Trujillo, ME}, title = {Micromonospora phytophila sp. nov. and Micromonospora luteiviridis sp. nov., isolated as natural inhabitants of plant nodules.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {248-253}, doi = {10.1099/ijsem.0.002490}, pmid = {29148367}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Micromonospora/*classification/genetics/isolation & purification ; Peas/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/*microbiology ; Sequence Analysis, DNA ; Spain ; }, abstract = {Two actinobacterial isolates, strains SG15T and SGB14T, were recovered through a microbial diversity study of nitrogen fixing nodules from Pisum sativum plants collected in Salamanca (Spain). The taxonomic status of these isolates was determined using a polyphasic approach and both presented chemotaxonomic and morphological properties consistent with their classification in the genus Micromonospora. For strains SG15T and SGB14T, the highest 16S rRNA gene sequence similarities were observed with Micromonospora coxensis JCM 13248T (99.2 %) and Micromonospora purpureochromogenes DSM 43821T (99.4 %), respectively. However, strains SG15T and SGB14T were readily distinguished from their phylogenetic neighbours both genetically and phenotypically indicating that they represent two new Micromonospora species. The following names are proposed for these species: Micromonosporaphytophila sp. nov. type strain SG15T (=CECT 9369T; =DSM 105363T), and Micromonosporaluteiviridis sp. nov. type strain SGB14T (=CECT 9370T; =DSM 105362T).}, } @article {pmid29148365, year = {2018}, author = {Park, S and Choi, J and Choi, SJ and Yoon, JH}, title = {Tenacibaculum insulae sp. nov., isolated from a tidal flat.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {228-233}, doi = {10.1099/ijsem.0.002487}, pmid = {29148365}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Islands ; Nucleic Acid Hybridization ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Seawater/*microbiology ; Sequence Analysis, DNA ; Tenacibaculum/*classification/genetics/isolation & purification ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile, non-spore-forming bacterial strain, designated JDTF-31T, was isolated from a tidal flat in Jindo, a South Korean island. Strain JDTF-31T grew optimally at 25 °C and in the presence of 2.0 % (w/v) NaCl. The neighbour-joining phylogenetic tree based on 16S rRNA gene sequences revealed that strain JDTF-31T fell within the cluster comprising the type strains of Tenacibaculum species, joining the type strain of Tenacibaculum soleae. The novel strain exhibited 16S rRNA gene sequence similarity values of 98.3, 97.8 and 97.1 % to the type strains of T. soleae, Tenacibaculum haliotisand Tenacibaculum ovolyticum, respectively, and of 94.2-96.8 % to the type strains of the other Tenacibaculum species. Strain JDTF-31T contained MK-6 as the predominant menaquinone and iso-C15 : 0 and iso-C15 : 0 3-OH as the major fatty acids. The major polar lipids of strain JDTF-31T were phosphatidylethanolamine, one unidentified lipid and one unidentified aminophospholipid. The DNA G+C content of strain JDTF-31T was 31.3 mol% and its DNA-DNA relatedness values with the type strains of T. soleae, T. haliotis and T. ovolyticum were 16-27 %. The differential phenotypic properties, together with its phylogenetic and genetic data, revealed that strain JDTF-31T is separated from other recognized species of the genus Tenacibaculum. On the basis of the data presented, strain JDTF-31T represents a novel species of the genus Tenacibaculum, for which the name Tenacibaculuminsulae sp. nov. is proposed. The type strain is JDTF-31T (=KCTC 52749T=NBRC 112783T).}, } @article {pmid29148364, year = {2018}, author = {Wang, YQ and Liu, XM and Tang, J and Yang, GQ and Yu, Z}, title = {Salibacterium lacus sp. nov., a halophilic, non-spore-forming bacterium isolated from sediment of a saline lake.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {113-117}, doi = {10.1099/ijsem.0.002467}, pmid = {29148364}, issn = {1466-5034}, mesh = {Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Lakes/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Salinity ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel halophilic bacterium, strain GSS13T, capable of growing at salinities of 8-28 % (w/v) NaCl (optimally at 24 %, w/v) was isolated from Yuncheng Saline Lake in China. GSS13T was Gram-stain-positive, strictly aerobic, rod-shaped, motile and a non-spore-former. Growth occurred at pH 5.5-8.5 (optimum pH 7.0) and at 10-45 °C (optimum 30 °C). On the basis of the results of 16S rRNA gene sequences phylogenetic analyses, GSS13T represents a member of the genus Salibacterium and is closely related to Salibacterium halotolerans S7T, Salibacterium qingdaonense CM1T and Salibacterium halochares MSS4T, with 16S rRNA gene sequence similarities of 98.7, 98.4 and 97.9 %, respectively. The results of DNA-DNA pairing studies revealed that GSS13T displayed 52, 43 and 48 % relatedness to S. halotolerans S7T, S. qingdaonense CM1T and S. halochares MSS4T, respectively. The polar lipids of GSS13 consisted of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol unidentified glycolipids, an unidentified phospholipid and an unidentified lipid. The predominant isoprenoid quinone was MK-7, and the major fatty acids were anteiso-C17 : 0 (32.0 %) and anteiso C15 : 0 (26.4 %). The DNA G+C content of the type strain was 52.1 mol%. On the basis of phylogenetic, chemotaxonomic and phenotypic data, a novel species of the genus Salibacterium is proposed, with the name Salibacterium lacus sp. nov. The type strain is GSS13T (=KCTC 33792T=MCCC 1K00567T).}, } @article {pmid29148363, year = {2018}, author = {Kang, JW and Choi, S and Choe, HN and Seong, CN}, title = {Hymenobacter defluvii sp. nov., isolated from wastewater of an acidic water neutralization facility.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {277-282}, doi = {10.1099/ijsem.0.002497}, pmid = {29148363}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Spermidine/analogs & derivatives/chemistry ; Tibet ; Vitamin K 2/analogs & derivatives/chemistry ; Waste Water/*microbiology ; }, abstract = {A non-motile, pink-coloured and rod-shaped bacterium, designated strain POA9T, was isolated from a wastewater treatment facility, Republic of Korea. Cells were Gram-reaction-negative, aerobic, catalase-positive and oxidase-negative. The major fatty acids were C16 : 1ω5c, iso-C15 : 0, summed feature 3 (C16 : 1ω6c and/or C16 : 1ω7c) and anteiso-C15 : 0. The strain contained MK-7 as the only isoprenoid quinone, phosphatidylethanolamine as the major polar lipid and sym-homospermidine as the major polyamine. The DNA G+C content was 57 mol%. A phylogenetic tree based on 16S rRNA gene sequences showed that strain POA9T forms a distinct evolutionary lineage within the radiation enclosing the members of the genus Hymenobacter, sharing the highest similarity with Hymenobacter actinosclerus CCUG 39621T (95.5 % sequence similarity) followed by Hymenobacterseoulensis 16F7GT (95.5 %), Hymenobactertibetensis XTM003T (95.4 %), Hymenobacterrutilus K2-33028T (95.4 %) and Hymenobacter psychrotolerans Tibet-IIU11T (94.9 %). A number of phenotypic characteristics distinguished strain POA9T from the related members of the genus Hymenobacter. On the basis of the evidence presented in this study, a novel species, Hymenobacter defluvii sp. nov., is proposed for strain POA9T (=KCTC 52270T=JCM 31658T).}, } @article {pmid29148362, year = {2018}, author = {Timilsina, S and Minsavage, GV and Preston, J and Newberry, EA and Paret, ML and Goss, EM and Jones, JB and Vallad, GE}, title = {Pseudomonas floridensis sp. nov., a bacterial pathogen isolated from tomato.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {64-70}, doi = {10.1099/ijsem.0.002445}, pmid = {29148362}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Lycopersicon esculentum/*microbiology ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; Plant Diseases/microbiology ; Pseudomonas/*classification/genetics/isolation & purification ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Solanum tuberosum/microbiology ; Tobacco/microbiology ; }, abstract = {An unusual fluorescent pseudomonad was isolated from tomato exhibiting leaf spot symptoms similar to bacterial speck. Strains were fluorescent, oxidase- and arginine-dihydrolase-negative, elicited a hypersensitive reaction on tobacco and produced a soft rot on potato slices. However, the strains produced an unusual yellow, mucoid growth on media containing 5 % sucrose that is not typical of levan. Based on multilocus sequence analysis using 16S rRNA, gap1, gltA, gyrB and rpoD, these strains formed a distinct phylogenetic group in the genus Pseudomonas and were most closely related to Pseudomonas viridiflava within the Pseudomonassyringae complex. Whole-genome comparisons, using average nucleotide identity based on blast, of representative strain GEV388T and publicly available genomes representing the genus Pseudomonas revealed phylogroup 7 P. viridiflava strain UASW0038 and P. viridiflava type strain ICMP 2848T as the closest relatives with 86.59 and 86.56 % nucleotide identity, respectively. In silico DNA-DNA hybridization using the genome-to-genome distance calculation method estimated 31.1 % DNA relatedness between GEV388T and P. viridiflava ATCC 13223T, strongly suggesting the strains are representatives of different species. These results together with Biolog GEN III tests, fatty acid methyl ester profiles and phylogenetic analysis using 16S rRNA and multiple housekeeping gene sequences demonstrated that this group represents a novel species member of the genus Pseudomonas. The name Pseudomonas floridensis sp. nov. is proposed with GEV388T (=LMG 30013T=ATCC TSD-90T) as the type strain.}, } @article {pmid29148360, year = {2018}, author = {Jani, K and Khare, K and Senik, S and Karodi, P and Vemuluri, VR and Bandal, J and Shouche, Y and Rale, V and Sharma, A}, title = {Corynebacterium godavarianum sp. nov., isolated from the Godavari river, India.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {241-247}, doi = {10.1099/ijsem.0.002491}, pmid = {29148360}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Corynebacterium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Humans ; India ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Religion ; Rivers/*microbiology ; Sequence Analysis, DNA ; *Water Microbiology ; }, abstract = {A Gram-stain-positive, rod-shaped, non-motile bacterium, strain PRD07T, was isolated from Godavari river, India during the world's largest spiritual and religious mass bathing event 'Kumbh Mela'. Molecular analysis using 16S rRNA gene sequencing and phylogenetic analysis reveals the distinct phylogenetic positioning of strain PRD07T within the genus Corynebacterium. The strain demonstrated highest sequence similarity to Corynebacterium imitans DSM 44264T (97.9 %), Corynebacterium appendicis DSM 44531T (97.1 %) and <96.7 % with all other members of the genus Corynebacterium. The G+C content of PRD07T was 68.5 mol% (Tm) and the DNA-DNA hybridization depicts 61.09 % genomic relatedness with C. imitans DSM 44264T. Chemotaxonomic assessment of strain PRD07T suggested presence of C16 : 0 (31.6 %), C18 : 0 (3.5 %) and C18 : 1ω9c (58.6 %) as the major cellular fatty acids. The major polar lipids of strain PRD07T were phosphatidylglycerol, diphosphatidylglycerol and glycophospholipid. Differentiating molecular, phylogenetic and chemotaxonomic characteristics of strain PRD07T with its closest relatives necessitated the description of strain PRD07T as a novel species of genus Corynebacterium for which the name Corynebacteriumgodavarianum sp. nov., has been proposed. The type strain is PRD07T (=MCC 3388T=KCTC 39803T=LMG 29598T).}, } @article {pmid29148359, year = {2018}, author = {Jung, HS and Lee, J and Hyeon, JW and Hyun, S and Jeon, CO}, title = {Albirhodobacter confluentis sp. nov., isolated from an estuary.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {289-293}, doi = {10.1099/ijsem.0.002499}, pmid = {29148359}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Estuaries ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative and strictly aerobic, moderately halophilic bacterium, designated strain S1-47T, was isolated from estuary sediment in South Korea. Cells were non-motile rods showing oxidase- and catalase-positive activities. Growth was observed at 10-30 °C (optimum, 25 °C), at pH 5.0-8.0 (optimum, pH 6.0-7.0) and in the presence of 0-6.0 % (w/v) NaCl (optimum, 2.0 %). Strain S1-47T contained summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c), summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c) and C16 : 0 as major cellular fatty acids and ubiquinone-10 as the sole isoprenoid quinone. Phosphatidylethanolamine, an unidentified aminolipid, an unidentified phospholipid and three unidentified lipids were detected as polar lipids. The G+C content of the genomic DNA was 69.3 mol%. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S1-47T formed a tight phylogenetic lineage with Albirhodobacter marinus N9T. Strain S1-47T was most closely related to Albirhodobactermarinus N9T with a 99.4 % 16S rRNA gene sequence similarity. DNA-DNA relatedness levels between strain S1-47T and the type strain of Albirhodobactermarinus were 49.8-52.2 %. Based on the phenotypic, chemotaxonomic and molecular features, strain S1-47T clearly represents a novel species of the genus Albirhodobacter, for which the name Albirhodobacter confluentis sp. nov. is proposed. The type strain is S1-47T (=KACC 18804T=JCM 31536T).}, } @article {pmid29147762, year = {2018}, author = {Liñeiro, E and Macias-Sánchez, AJ and Espinazo, M and Cantoral, JM and Moraga, J and Collado, IG and Fernández-Acero, FJ}, title = {Phenotypic Effects and Inhibition of Botrydial Biosynthesis Induced by Different Plant-Based Elicitors in Botrytis cinerea.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {431-440}, pmid = {29147762}, issn = {1432-0991}, support = {DGICYT-AGL2015-65684-C2-1/2//Secretaría de Estado de Investigación, Desarrollo e Innovación/ ; 2010-15//Universidad de Cádiz/ ; }, mesh = {Aldehydes/*metabolism ; Botrytis/genetics/*metabolism ; Bridged Bicyclo Compounds/*metabolism ; Fungal Proteins/genetics/metabolism ; Gene Expression Regulation, Fungal ; Host-Pathogen Interactions ; Lycopersicon esculentum/*microbiology ; Mycotoxins/*metabolism ; Plant Diseases/*microbiology ; }, abstract = {Botrytis cinerea is considered a model organism for the study of plant-pathogen interaction showing great genetic diversity and a high degree of morphological variability depending on environmental conditions. The use of new compounds and plant-based elicitors may trigger the expression of different B. cinerea genes, providing new sources of virulence factors. This work is focused on elucidating the phenotypic effect in B. cinerea of different carbon sources such as glucose, cellulose and tomato cell walls (TCW). Production of botrydial and dihydrobotrydial toxins was evaluated using thin-layer chromatography (TLC), proton nuclear magnetic resonance spectroscopy (1H-NMR) and mass spectrometry (UPLC-HRESIMS). Expression of the toxin biosynthesis gene BcBOT2 was followed using RT-qPCR. Results show an inhibition of the toxin biosynthesis pathway when TCW are present as a sole carbon source, suggesting that the toxin is only produced when rich molecules, like glucose, are available for fungal metabolism. That suggests a connection between gene expression of virulence factors and environmental conditions, where the silent genes can be induced by different culture conditions.}, } @article {pmid29146999, year = {2018}, author = {Courchamp, F and Bradshaw, CJA}, title = {Publisher Correction: 100 articles every ecologist should read.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {403}, doi = {10.1038/s41559-017-0416-z}, pmid = {29146999}, issn = {2397-334X}, abstract = {This Article originally suggested that readers may be able to source PDF files of the papers analysed via a website that is involved in litigation over breach of copyright. This suggestion and the related URL have now been removed.}, } @article {pmid29146414, year = {2018}, author = {McDowell, NG and Michaletz, ST and Bennett, KE and Solander, KC and Xu, C and Maxwell, RM and Middleton, RS}, title = {Predicting Chronic Climate-Driven Disturbances and Their Mitigation.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {1}, pages = {15-27}, doi = {10.1016/j.tree.2017.10.002}, pmid = {29146414}, issn = {1872-8383}, mesh = {*Adaptation, Biological ; *Climate Change ; *Conservation of Natural Resources ; *Ecosystem ; Models, Biological ; }, abstract = {Society increasingly demands the stable provision of ecosystem resources to support our population. Resource risks from climate-driven disturbances, including drought, heat, insect outbreaks, and wildfire, are growing as a chronic state of disequilibrium results from increasing temperatures and a greater frequency of extreme events. This confluence of increased demand and risk may soon reach critical thresholds. We explain here why extreme chronic disequilibrium of ecosystem function is likely to increase dramatically across the globe, creating no-analog conditions that challenge adaptation. We also present novel mechanistic theory that combines models for disturbance mortality and metabolic scaling to link size-dependent plant mortality to changes in ecosystem stocks and fluxes. Efforts must anticipate and model chronic ecosystem disequilibrium to properly prepare for resilience planning.}, } @article {pmid29146383, year = {2018}, author = {Papanicolas, LE and Gordon, DL and Wesselingh, SL and Rogers, GB}, title = {Not Just Antibiotics: Is Cancer Chemotherapy Driving Antimicrobial Resistance?.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {393-400}, doi = {10.1016/j.tim.2017.10.009}, pmid = {29146383}, issn = {1878-4380}, mesh = {Anti-Bacterial Agents/*pharmacology ; Antineoplastic Agents/*pharmacology ; Bacteria/drug effects/genetics ; DNA Damage ; Drug Combinations ; Drug Resistance, Bacterial/*drug effects/genetics ; Dysbiosis/microbiology ; Gastrointestinal Microbiome/drug effects ; Gene Transfer, Horizontal ; Humans ; Mutagenesis ; Neoplasms/complications/drug therapy ; Sepsis/microbiology ; Symbiosis/drug effects ; }, abstract = {The global spread of antibiotic-resistant pathogens threatens to increase the mortality of cancer patients significantly. We propose that chemotherapy contributes to the emergence of antibiotic-resistant bacteria within the gut and, in combination with antibiotics, drives pathogen overgrowth and translocation into the bloodstream. In our model, these processes are mediated by the effects of chemotherapy on bacterial mutagenesis and horizontal gene transfer, the disruption of commensal gut microbiology, and alterations to host physiology. Clinically, this model manifests as a cycle of recurrent sepsis, with each episode involving ever more resistant organisms and requiring increasingly broad-spectrum antimicrobial therapy. Therapies that restore the gut microbiota following chemotherapy or antibiotics could provide a means to break this cycle of infection and treatment failure.}, } @article {pmid29146106, year = {2018}, author = {Aron, Z and Opperman, TJ}, title = {The hydrophobic trap-the Achilles heel of RND efflux pumps.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {393-400}, pmid = {29146106}, issn = {1769-7123}, support = {R44 AI100332/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/chemistry/pharmacology ; Bacterial Proteins/antagonists & inhibitors/*chemistry/genetics/metabolism ; Binding Sites ; Drug Design ; Drug Resistance, Multiple, Bacterial ; Gram-Negative Bacteria/chemistry/drug effects/genetics/*metabolism ; Hydrophobic and Hydrophilic Interactions ; Membrane Transport Proteins/*chemistry/genetics/metabolism ; Multigene Family ; }, abstract = {Resistance-nodulation-division (RND) superfamily efflux pumps play a major role in multidrug resistance (MDR) of Gram-negative pathogens by extruding diverse classes of antibiotics from the cell. There has been considerable interest in developing efflux pump inhibitors (EPIs) of RND pumps as adjunctive therapies. The primary challenge in EPI discovery has been the highly hydrophobic, poly-specific substrate binding site of the target. Recent findings have identified the hydrophobic trap, a narrow phenylalanine-lined groove in the substrate-binding site, as the "Achilles heel" of the RND efflux pumps. In this review, we will examine the hydrophobic trap as an EPI target and two chemically distinct series of EPIs that bind there.}, } @article {pmid29146006, year = {2018}, author = {}, title = {Expression of concern on 'The oldest hominin butchery in European mid-latitudes at the Jaramillo site of Untermassfeld (Thuringia, Germany)'.}, journal = {Journal of human evolution}, volume = {116}, number = {}, pages = {108}, doi = {10.1016/j.jhevol.2017.11.001}, pmid = {29146006}, issn = {1095-8606}, } @article {pmid29145592, year = {2018}, author = {Koyama, A and Steinweg, JM and Haddix, ML and Dukes, JS and Wallenstein, MD}, title = {Soil bacterial community responses to altered precipitation and temperature regimes in an old field grassland are mediated by plants.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix156}, pmid = {29145592}, issn = {1574-6941}, abstract = {The structure and function of soil microbiomes often change in response to experimental climate manipulations, suggesting an important role in ecosystem feedbacks. However, it is difficult to know if microbes are responding directly to environmental changes or are more strongly impacted by plant responses. We investigated soil microbial responses to precipitation and temperature manipulations at the Boston-Area Climate Experiment in Massachusetts, USA, in both vegetated and bare plots to parse direct vs. plant-mediated responses to multi-factor climate change. We assessed the bacterial community in vegetated soils in 2009, two years after the experiment was initiated, and bacterial and fungal community in vegetated and bare soils in 2011. The bacterial community structure was significantly changed by the treatments in vegetated soils. However, such changes in the bacterial community across the treatments were absent in the 2011 bare soils. These results suggest that the bacterial communities in vegetated soils were structured via plant community shifts in response to the abiotic manipulations. Co-variation between bacterial community structure and temperature sensitivities and stoichiometry of potential enzyme activities in the 2011 vegetated soils suggested a link between bacterial community structure and ecosystem function. This study emphasizes the importance of plant-soil-microbial interactions in mediating responses to future climate change.}, } @article {pmid29145209, year = {2018}, author = {D'Alberton, F and Vissani, S and Ferracuti, C and Pasterski, V}, title = {Methodological Issues for Psychological Evaluation across the Lifespan of Individuals with a Difference/Disorder of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {123-134}, doi = {10.1159/000484189}, pmid = {29145209}, issn = {1661-5433}, mesh = {Communication ; Disorders of Sex Development/*psychology ; Humans ; *Longevity ; *Psychological Techniques ; Terminology as Topic ; }, abstract = {The aim of the current report is to provide guidance relevant to psychological evaluation for healthcare providers and researchers working in the field of disorders of sexual development (DSD). In doing so, we give careful consideration to methodological issues and limitations that may influence the utility of investigations. For example, rarity and heterogeneity of DSD conditions restrict sample sizes when conducting evaluations aimed at establishing condition-specific psychological outcomes. At the same time, the potential for stigmatization by virtue of conducting psychological evaluations is particularly high given the fundamental contribution of sex and gender to one's sense of self and integrity. This article will provide basic theory for psychological evaluation as well as give a review of specific measures that can be employed for clinical purposes depending on a variety of parameters, including life stage of the patient and goal(s) of the evaluation. Care providers and service users may benefit from guidance in coping with the difficulties inherent in having and/or treating DSD. The potential for identification with the patient with DSD is higher than in other domains of medicine because sexual and gender identities are fundamental to all humans and are continually evolving from a sociological perspective.}, } @article {pmid29145200, year = {2018}, author = {Croft, B and Ohnesorg, T and Sinclair, AH}, title = {The Role of Copy Number Variants in Disorders of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {19-29}, doi = {10.1159/000481896}, pmid = {29145200}, issn = {1661-5433}, mesh = {Chromosome Mapping ; DNA Copy Number Variations/*genetics ; Disorders of Sex Development/*genetics ; High-Throughput Nucleotide Sequencing ; Humans ; Open Reading Frames/genetics ; Regulatory Sequences, Nucleic Acid/genetics ; }, abstract = {Despite considerable research effort and significant advances in sequencing technologies, the majority of disorders of sex development (DSD) cases still lack a molecular genetic diagnosis. While coding variants have been discovered in known and candidate DSD genes, comparatively little is known about copy number variations (CNVs) affecting both coding and noncoding regions. Due to rapidly falling costs of whole genome sequencing, many more CNVs in individuals with DSD will be identified. These CNVs may explain a significant number of hitherto undiagnosed cases of DSD. In this review, we provide an overview of CNVs that are known to cause DSD and discuss approaches to identify and verify causative CNVs.}, } @article {pmid29144774, year = {2018}, author = {Douglas, AE}, title = {Strategies for Enhanced Crop Resistance to Insect Pests.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {637-660}, doi = {10.1146/annurev-arplant-042817-040248}, pmid = {29144774}, issn = {1545-2123}, abstract = {Insect pests are responsible for substantial crop losses worldwide through direct damage and transmission of plant diseases, and novel approaches that complement or replace broad-spectrum chemical insecticides will facilitate the sustainable intensification of food production in the coming decades. Multiple strategies for improved crop resistance to insect pests, especially strategies relating to plant secondary metabolism and immunity and microbiome science, are becoming available. Recent advances in metabolic engineering of plant secondary chemistry offer the promise of specific toxicity or deterrence to insect pests; improved understanding of plant immunity against insects provides routes to optimize plant defenses against insects; and the microbiomes of insect pests can be exploited, either as a target or as a vehicle for delivery of insecticidal agents. Implementation of these advances will be facilitated by ongoing advances in plant breeding and genetic technologies.}, } @article {pmid29143964, year = {2018}, author = {Feiner, N and Rago, A and While, GM and Uller, T}, title = {Signatures of selection in embryonic transcriptomes of lizards adapting in parallel to cool climate.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {67-81}, doi = {10.1111/evo.13397}, pmid = {29143964}, issn = {1558-5646}, abstract = {Populations adapting independently to the same environment provide important insights into the repeatability of evolution at different levels of biological organization. In the 20th century, common wall lizards (Podarcis muralis) from southern and western Europe were introduced to England, north of their native range. Nonnative populations of both lineages have adapted to the shorter season and lower egg incubation temperature by increasing the absolute rate of embryonic development. Here, we tested if this adaptation is accompanied by signatures of directional selection in the transcriptomes of early embryos and, if so, if nonnative populations show adaptive convergence. Embryos from nonnative populations exhibited gene expression profiles consistent with directional selection following introduction, but different genes were affected in the two lineages. Despite this, the functional enrichment of genes that changed their expression following introduction showed substantial similarity between lineages, and was consistent with mechanisms that should promote developmental rate. Moreover, the divergence between nonnative and native populations was enriched for genes that were temperature-responsive in native populations. These results indicate that small populations are able to adapt to new climatic regimes, but the means by which they do so may largely be determined by founder effects and other sources of genetic drift.}, } @article {pmid29143876, year = {2018}, author = {Sriraman, K and Nilgiriwala, K and Saranath, D and Chatterjee, A and Mistry, N}, title = {Deregulation of Genes Associated with Alternate Drug Resistance Mechanisms in Mycobacterium tuberculosis.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {394-400}, pmid = {29143876}, issn = {1432-0991}, support = {SB/SO/HS-0065/2013//Department of Science and Technology, Government of India/ ; }, mesh = {Antitubercular Agents/*pharmacology ; Bacterial Proteins/genetics/metabolism ; Down-Regulation/drug effects ; *Drug Resistance, Multiple, Bacterial ; Gene Expression Regulation, Bacterial/drug effects ; Humans ; Isoniazid/pharmacology ; Microbial Sensitivity Tests ; Mycobacterium tuberculosis/*drug effects/genetics/metabolism ; Rifampin/pharmacology ; Tuberculosis/drug therapy/*microbiology ; }, abstract = {Alternate mechanisms of drug resistance involving intrinsic defense pathways play an important role in development of drug resistance. Deregulation of drug efflux, cellular metabolism, and DNA repair have been indicated to have effect on drug tolerance and persistence. Here we chose eight genes from these pathways to investigate their association with development of multidrug resistance (MDR). We generated mono drug resistant and MDR strains of rifampicin and isoniazid and examined the differential expression of genes belonging to efflux, DNA repair and cell wall lipid synthesis pathways. Rv1687c, recB, ppsD and embC genes showed significant (P <0.05) upregulation in mono-resistant (both rifampicin and isoniazid) as well as MDR strains. mmr showed significant upregulation with rifampicin resistance while Rv1457c showed significant upregulation only with mono-resistant strains. Highest expression change was observed with Rv1687c and ppsD. The study identified potential key genes that are significantly associated with development of drug resistance in vitro. These genes may help identify clinical strains predisposed to acquiring drug resistance in patients during the course of treatment or help in management of MDR forms of tuberculosis.}, } @article {pmid29143730, year = {2018}, author = {Degefu, T and Wolde-Meskel, E and Rasche, F}, title = {Genetic diversity and symbiotic effectiveness of Bradyrhizobium strains nodulating selected annual grain legumes growing in Ethiopia.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {449-460}, doi = {10.1099/ijsem.0.002486}, pmid = {29143730}, issn = {1466-5034}, mesh = {Arachis/microbiology ; Bacterial Typing Techniques ; Base Composition ; Bradyrhizobium/*classification/physiology ; DNA, Bacterial/genetics ; Ethiopia ; Fabaceae/*microbiology ; Genes, Bacterial ; Genetic Variation ; Multilocus Sequence Typing ; *Phylogeny ; *Plant Root Nodulation ; RNA, Ribosomal, 16S/genetics ; Root Nodules, Plant/microbiology ; Sequence Analysis, DNA ; *Symbiosis ; Vigna/microbiology ; }, abstract = {Vigna unguiculata, Vigna radiata and Arachis hypogaea growing in Ethiopia are nodulated by a genetically diverse group of Bradyrhizobium strains. To determine the genetic identity and symbiotic effectiveness of these bacteria, a collection of 36 test strains originating from the root nodules of the three hosts was investigated using multilocus sequence analyses (MLSA) of core genes including 16S rRNA, recA, glnII, gyrB, atpD and dnaK. Sequence analysis of nodA and nifH genes along with tests for symbiotic effectiveness using δ15N analysis were also carried out. The phylogenetic trees derived from the MLSA grouped most test strains into four well-supported distinct positions designated as genospecies I-IV. The maximum likelihood (ML) tree that was constructed based on the nodA gene sequences separated the entire test strains into two lineages, where the majority of the test strains were clustered on one of a well-supported large branch that comprise Bradyrhizobium species from the tropics. This clearly suggested the monophyletic origin of the nodA genes within the bradyrhizobia of tropical origin. The δ15N-based symbiotic effectiveness test of seven selected strains revealed that strains GN100 (δ15N=0.73) and GN102 (δ15N=0.79) were highly effective nitrogen fixers when inoculated to cowpea, thus can be considered as inoculants in cowpea production. It was concluded that Ethiopian soils are a hotspot for rhizobial diversity. This calls for further research to unravel as yet unknown bradyrhizobia nodulating legume host species growing in the country. In this respect, prospective research should also address the mechanisms of symbiotic specificity that could lead to high nitrogen fixation in target legumes.}, } @article {pmid29143729, year = {2018}, author = {Sheu, DS and Sheu, SY and Xie, PB and Tang, SL and Chen, WM}, title = {Thalassotalea coralli sp. nov., isolated from the torch coral Euphyllia glabrescens.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {185-191}, doi = {10.1099/ijsem.0.002478}, pmid = {29143729}, issn = {1466-5034}, mesh = {Animals ; Anthozoa/*microbiology ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Hydroxybutyrates ; Nucleic Acid Hybridization ; Phosphatidylglycerols/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Polyesters ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Taiwan ; Ubiquinone/chemistry ; }, abstract = {Strain Eup a-8T, isolated from a torch coral Euphyllia glabrescens, was characterized using a polyphasic taxonomy approach. Cells of strain Eup a-8T were Gram-staining-negative, aerobic, motile by means of a single polar flagellum, poly-β-hydroxybutyrate-containing, rod-shaped and formed white colonies. Optimal growth occurred at 25-30 °C, pH 7-8, and in the presence of 2 % NaCl. Phylogenetic analyses based on 16S rRNA gene sequences showed that strain Eup a-8T belonged to the genus Thalassotalea and showed the highest levels of sequence similarity with respect to Thalassotalea ganghwensis JC2041T (97.1 %). Strain Eup a-8T contained C17 : 1ω8c, summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c), iso-C14 : 0 and iso-C16 : 0 as the predominant fatty acids. The only isoprenoid quinone was Q-8. The major polar lipids were phosphatidylethanolamine, phosphatidylglycerol and one uncharacterized phospholipid. Genomic DNA G+C content of strain Eup a-8T was 41.5 mol%. The DNA-DNA hybridization value for strain Eup a-8T with Thalassotalea ganghwensis JC2041T was less than 70 %. Differential phenotypic properties, together with the phylogenetic inference, demonstrate that strain Eup a-8T should be classified as a novel species of the genus Thalassotalea, for which the name Thalassotalea coralli sp. nov. is proposed. The type strain is Eup a-8T (=BCRC 80967T=LMG 29478T=KCTC 52169T).}, } @article {pmid29143728, year = {2018}, author = {Zhao, J and Shi, L and Li, W and Wang, J and Wang, H and Tian, Y and Xiang, W and Wang, X}, title = {Streptomyces tritici sp. nov., a novel actinomycete isolated from rhizosphere soil of wheat (Triticum aestivum L.).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {492-497}, doi = {10.1099/ijsem.0.002493}, pmid = {29143728}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Streptomyces/*classification/genetics/isolation & purification ; Triticum/*microbiology ; Vitamin K 2/chemistry ; }, abstract = {Two novel actinomycete isolates, designated strains NEAU-A4T and NEAU-A3, were isolated from rhizosphere soil of wheat (Triticumaestivum L.) and characterized using a polyphasic approach. Morphological and chemotaxonomic characteristics of the two strains coincided with those of the genus Streptomyces. The 16S rRNA gene sequence analysis showed that the two isolates exhibited 99.6 % 16S rRNA gene sequence similarity with each other and that they were most closely related to Streptomyces violaceorectus DSM 40279T (98.8, 99.0 %). Phylogenetic analysis based on 16S rRNA gene sequences indicated that the two strains clustered together and formed a separate subclade. Furthermore, a combination of DNA-DNA hybridization results and some physiological and biochemical properties demonstrated that the two strains could be distinguished from its closest relative. Therefore, it is proposed that strains NEAU-A4T and NEAU-A3 should be classified as representatives of a novel species of the genus Streptomyces, for which the name Streptomycestritici sp. nov. is proposed. The type strain is NEAU-A4T (=CGMCC 4.7393T=DSM 104540T).}, } @article {pmid29143725, year = {2018}, author = {Wang, Y and Liu, T and Ming, H and Sun, P and Cao, C and Guo, M and Du, J and Zhou, C and Zhu, W}, title = {Thalassotalea atypica sp. nov., isolated from seawater, and emended description of Thalassotalea eurytherma.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {271-276}, doi = {10.1099/ijsem.0.002495}, pmid = {29143725}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Gammaproteobacteria/*classification/genetics/isolation & purification ; Phosphatidylethanolamines/chemistry ; Phosphatidylglycerols/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A novel Gram-stain-negative, straight or slightly curved rod-shaped, non-spore-forming, non-flagellated, strictly aerobic strain, designated RZG4-3-1T, was isolated from coastal seawater of Rizhao, China (119.625° E 35.517° N). The organism grew optimally at 24-28 °C, at pH 7.0 and in the presence of 2.0 % (w/v) NaCl. The strain required seawater or artificial seawater for growth, and NaCl alone did not support growth. Strain RZG4-3-1T contained ubiquinone 8 (Q-8) as the major respiratory quinone and contained C16 : 1ω7c and/or C16 : 1ω6c and C16 : 0 as the dominant fatty acids. The polar lipids of strain RZG4-3-1T were phosphatidylethanolamine, phosphatidylglycerol and one unidentified aminophospholipid. The DNA G+C content of strain RZG4-3-1T was 40.1 mol%. Strain RZG4-3-1T exhibited the highest 16S rRNA gene sequence similarity value (96.0 %) to Thalassotalea eurytherma JCM 18482T. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain RZG4-3-1T belonged to the genus Thalassotalea. On the basis of polyphasic analyses, strain RZG4-3-1T represents a novel species of the genus Thalassotalea, for which the name Thalassotalea atypica sp. nov. is proposed. The type strain is RZG4-3-1T (=JCM 31894T=KCTC 52745T=MCCC 1K03276T). An emended description of Thalassotalea eurytherma is also provided.}, } @article {pmid29143302, year = {2018}, author = {Castiglione, GM and Schott, RK and Hauser, FE and Chang, BSW}, title = {Convergent selection pressures drive the evolution of rhodopsin kinetics at high altitudes via nonparallel mechanisms.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {170-186}, doi = {10.1111/evo.13396}, pmid = {29143302}, issn = {1558-5646}, abstract = {Convergent evolution in response to similar selective pressures is a well-known phenomenon in evolutionary biology. Less well understood is how selection drives convergence in protein function, and the underlying mechanisms by which this can be achieved. Here, we investigate functional convergence in the visual system of two distantly related lineages of high-altitude adapted Andean and Himalayan catfishes. Statistical analyses revealed in the two high-altitude lineages, a parallel acceleration of evolutionary rates in rhodopsin, the dim-light visual pigment. However, the elevated rates were found to be accompanied by substitutions at different sites in the protein. Experiments substituting Andean- or Himalayan-specific residues significantly accelerated the kinetic rates of rhodopsin, destabilizing the ligand-bound forms. As found in cold-adapted enzymes, this phenotype likely compensates for a cold-induced decrease in kinetic rates, properties of rhodopsin mediating rod sensitivity and visual performance. Our study suggests that molecular convergence in protein function can be driven by parallel shifts in evolutionary rates but via nonparallel molecular mechanisms. Signatures of natural selection may therefore be a powerful guide for identifying complex instances of functional convergence across a wider range of protein systems.}, } @article {pmid29141238, year = {2018}, author = {González-Prieto, C and Lesser, CF}, title = {Rationale redesign of type III secretion systems: toward the development of non-pathogenic E. coli for in vivo delivery of therapeutic payloads.}, journal = {Current opinion in microbiology}, volume = {41}, number = {}, pages = {1-7}, pmid = {29141238}, issn = {1879-0364}, support = {R01 AI064285/AI/NIAID NIH HHS/United States ; R01 DK113599/DK/NIDDK NIH HHS/United States ; R56 AI064285/AI/NIAID NIH HHS/United States ; }, mesh = {Drug Delivery Systems/*methods ; Escherichia coli/genetics/*metabolism/pathogenicity ; Escherichia coli Proteins ; Gene Expression Regulation, Bacterial ; Gram-Negative Bacteria/genetics/metabolism/pathogenicity ; Type III Secretion Systems/genetics/*therapeutic use ; Virulence/genetics ; }, abstract = {Transkingdom secretion systems that bacteria use to inject proteins directly into the cytosol of mammalian host cells play an essential role in the virulence of many Gram-negative bacterial pathogens. Current efforts are underway to repurpose these machines as novel therapeutics; type III secretion systems as vectors for the delivery of proteins of therapeutic value including heterologous antigens for vaccine development and type IV secretion systems as vectors for DNA. While initial studies focused on the use of attenuated or replication incompetent pathogens, the recent development of non-pathogenic Escherichia coli that encode programmable type III secretion systems expands possibilities for the in vivo directed delivery of therapeutic payloads.}, } @article {pmid29140727, year = {2018}, author = {Kreiner, JM and Stinchcombe, JR and Wright, SI}, title = {Population Genomics of Herbicide Resistance: Adaptation via Evolutionary Rescue.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {611-635}, doi = {10.1146/annurev-arplant-042817-040038}, pmid = {29140727}, issn = {1545-2123}, abstract = {The evolution of herbicide resistance in weed populations is a highly replicated example of adaptation surmounting the race against extinction, but the factors determining its rate and nature remain poorly understood. Here, we explore theory and empirical evidence for the importance of population genetic parameters-including effective population size, dominance, mutational target size, and gene flow-in influencing the probability and mode of herbicide resistance adaptation and its variation across species. We compiled data on the number of resistance mutations across populations for 79 herbicide-resistant species. Our findings are consistent with theoretical predictions that self-fertilization reduces resistance adaptation from standing variation within populations, but increases independent adaptation across populations. Furthermore, we provide evidence for a ploidy-mating system interaction that may reflect trade-offs in polyploids between increased effective population size and greater masking of beneficial mutations. We highlight the power of population genomic approaches to provide insights into the evolutionary dynamics of herbicide resistance with important implications for understanding the limits of adaptation.}, } @article {pmid29139350, year = {2018}, author = {Chaudhary, DK and Dahal, RH and Kim, J}, title = {Nemorella caseinilytica gen. nov., sp. nov., isolated from forest soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {2}, pages = {474-481}, doi = {10.1099/ijsem.0.002427}, pmid = {29139350}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; *Forests ; Phosphatidylethanolamines/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Spermidine/chemistry ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {Two novel strains, J116-2T and J116-1, were isolated from forest soil and were taxonomically characterized by a polyphasic approach. Both strains were yellow-coloured, Gram-stain-negative, strictly aerobic, non-motile and rod-shaped bacteria. The strains were non-sporulating, catalase-positive and oxidase-negative. Strains J116-2T and J116-1 were able to grow at 20-32 °C, pH 6.0-8.5, and 0-0.5 % (w/v) NaCl concentration. Based on 16S rRNA gene sequence analyses, strains J116-2T and J116-1 formed a distinct lineage within the family Chitinophagaceae of the phylum Bacteroidetes and were closely related to genera Taibaiella (89.86-89.30 % sequence similarity), Falvihumibacter (89.20-89.06 %), Filimonas (89.06 %) and Chitinophaga(89.01-88.77 %). The pairwise sequence similarity between strains J116-2T and J116-1 was found to be 99.86 %. Flexirubin-type pigments were absent in both strains. The only respiratory quinone was menaquinone-7 (MK-7); the major polar lipid was phosphatidylethanolamine; the predominant polyamine was homospermidine; and the major fatty acids were C15 : 0iso, C15 : 1iso G and C17 : 0iso 3-OH. The genomic DNA G+C content values of strains J116-2T and J116-1 were 51.1 and 50.9 mol%, respectively. On the basis of phenotypic, genotypic and phylogenetic analysis, strain J116-2T represents a novel species of a new genus in the family Chitinophagaceae, for which the name Nemorella caseinilytica gen. nov., sp. nov. is proposed. The type strain of Nemorella caseinilytica is J116-2T (=KEMB 9005-550T=KACC 19168T=NBRC 112827T).}, } @article {pmid29139349, year = {2018}, author = {Sun, LN and Pan, DD and Wu, XW and Yang, ED and Hua, RM and Li, QX}, title = {Leucobacter triazinivorans sp. nov., a s-triazine herbicide prometryn-degrading bacterium isolated from sludge.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {204-210}, doi = {10.1099/ijsem.0.002483}, pmid = {29139349}, issn = {1466-5034}, mesh = {Actinomycetales/*classification/genetics/isolation & purification ; Aminobutyrates ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Herbicides/*metabolism ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; Prometryne/*metabolism ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sewage/*microbiology ; Vitamin K 2/chemistry ; }, abstract = {A Gram-stain-positive, rod-shaped, non-motile bacterial strain, designated JW-1T, was isolated from activated sludge collected from the outlet of an aeration tank in a prometryn-manufacturing plant, located in Binzhou City, Shandong province, PR China. Phylogenetic analysis, based on 16S rRNA gene sequences, indicated that strain JW-1T belongs to the genus Leucobacter and its closest neighbours are 'Leucobacter kyeonggiensis' F3-P9 (98.95 % similarity), Leucobacter celer subsp. astrifaciens CBX151T (98.62 %), Leucobacter celer subsp. celer NAL101T (98.53 %), Leucobacter chromiiresistens JG31T (97.86 %) and Leucobacter chironomi DSM 19883T (97.37 %). DNA-DNA hybridization values with the above strains were <55 %. The DNA G+C content of strain JW-1T was 72.6 mol%. The major fatty acids of strain JW-1T were iso-C16 : 0, anteiso-C15 : 0, anteiso-C17 : 0 and iso-C15 : 0. The predominant polar lipids were diphosphatidylglycerol, phosphatidylglycerol and glycolipid. The predominant menaquinone was MK-11. The cell wall amino acids were 2,4-diaminobutyric acid, alanine, glutamic acid, glycine and threonine. Based on the molecular and chemotaxonomic data, as well as the physiological and biochemical characteristics, strain JW-1T is considered to represent a novel species of the genus Leucobacter, for which the name Leucobacter triazinivorans is proposed. The type strain is JW-1T (=DSM 105188T=LMG 30083T).}, } @article {pmid29139347, year = {2018}, author = {Feng, T and Jeong, SE and Kim, KH and Park, HY and Jeon, CO}, title = {Aestuariicoccus marinus gen. nov., sp. nov., isolated from sea-tidal flat sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {260-265}, doi = {10.1099/ijsem.0.002494}, pmid = {29139347}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Rhodobacteraceae/*classification/genetics/isolation & purification ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, strictly aerobic and halotolerant bacterial strain, designated strain NAP41T, was isolated from a sea tidal flat in the Yellow Sea of South Korea. Cells were non-motile cocci showing oxidase- and catalase-positive activities. Growth of strain NAP41T was observed at 15-40 °C (optimum, 37 °C), at pH 6.5-9.0 (optimum, pH 7.0-7.5) and in the presence of 0.5-12 % (w/v) NaCl (optimum, 2 %). Strain NAP41T contained summed feature 8 (comprising C18 : ω7c/C18 : 1ω6c) and C18 : 0 as the major fatty acids and ubiquinone-10 as the sole isoprenoid quinone. Phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, an unidentified aminolipid and three unidentified lipids were detected as the polar lipids. The G+C content of the genomic DNA was 56.0 mol%. Strain NAP41T was most closely related to Primorskyibacter insulae SSK3-2T, Thalassococcus lentus YCS-24T and Roseivivax lentus DSM 29430T with 96.67, 96.39 and 96.39 % 16S rRNA gene sequence similarities, respectively, and formed a phylogenetic lineage distinct from closely related taxa within the family Rhodobacteraceae with low bootstrap values. On the basis of phenotypic, chemotaxonomic and molecular properties, strain NAP41T represents a novel species of a novel genus of the family Rhodobacteraceae, for whichthe name Aestuariicoccus marinus gen. nov., sp. nov. is proposed. The type strain of the type species is NAP41T (KACC 18431T=JCM 30739T).}, } @article {pmid29139343, year = {2018}, author = {Tortoli, E and Kohl, TA and Brown-Elliott, BA and Trovato, A and Cardoso-Leão, S and Garcia, MJ and Vasireddy, S and Turenne, CY and Griffith, DE and Philley, JV and Niemann, S and Wallace, RJ and Cirillo, DM}, title = {Mycobacterium abscessus, a taxonomic puzzle.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {467-469}, doi = {10.1099/ijsem.0.002457}, pmid = {29139343}, issn = {1466-5034}, mesh = {Anti-Bacterial Agents ; *Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial ; Fatty Acids ; *Mycobacterium abscessus ; Nontuberculous Mycobacteria/genetics ; Phylogeny ; RNA, Ribosomal, 16S ; Sequence Analysis, DNA ; }, } @article {pmid29137957, year = {2018}, author = {Saunders, GW and Jackson, C and Salomaki, ED}, title = {Phylogenetic analyses of transcriptome data resolve familial assignments for genera of the red-algal Acrochaetiales-Palmariales Complex (Nemaliophycidae).}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {151-159}, doi = {10.1016/j.ympev.2017.11.002}, pmid = {29137957}, issn = {1095-9513}, mesh = {Base Sequence ; DNA Barcoding, Taxonomic ; DNA, Intergenic/genetics ; Likelihood Functions ; Mitochondria/genetics ; *Phylogeny ; Rhodophyta/*classification/*genetics ; Transcriptome/*genetics ; }, abstract = {Phylogenetic analyses of transcriptome data for representatives of the red algal Acrochaetiales-Palmariales Complex provided robust support for the assignment of genera to the constituent families. In the Acrochaetiales, the genera Acrochaetium, Grania, and an unnamed genus-level lineage (Acrochaetiac sp._1Aus) were assigned to the Acrochaetiaceae, while Audouinella is placed in a resurrected Audouinellaceae and Rhodochorton and Rhododrewia constitute the resurrected Rhodochortonaceae. For the Palmariales, transcriptome data solidly support the inclusion of Camontagnea and Rhodothamniella in the Rhodothamniellaceae, Meiodiscus and Rubrointrusa in the Meiodiscaceae, Rhodonematella and Rhodophysema in the Rhodophysemataceae, while Devaleraea and Palmaria remained in the Palmariaceae. These analyses, however, questioned the monophyly of Palmaria, which prompted a second round of analyses using eight common red algal phylogenetic markers and including a broader sampling of red algal genera in our analyses. These results supported transfer of Palmaria callophylloides and P. mollis to the genus Devaleraea necessitating new combinations, and further added the genus Halosaccion to the Palmariaceae and the genera Kallymenicola and Rhodophysemopsis to the Meiodiscaceae. Finally, DNA barcode (mitochondrial COI-5P) and ITS data were explored and supported the continued recognition of Palmaria palmata as a single species in the North Atlantic.}, } @article {pmid29137925, year = {2018}, author = {Fujimura, N and Kuzelova, A and Ebert, A and Strnad, H and Lachova, J and Machon, O and Busslinger, M and Kozmik, Z}, title = {Polycomb repression complex 2 is required for the maintenance of retinal progenitor cells and balanced retinal differentiation.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {47-60}, doi = {10.1016/j.ydbio.2017.11.004}, pmid = {29137925}, issn = {1095-564X}, mesh = {Animals ; Cell Differentiation/physiology ; Cell Proliferation ; Chromatin/metabolism ; Enhancer of Zeste Homolog 2 Protein/metabolism ; Histones/metabolism ; Methylation ; Mice ; Neurogenesis ; Neuroglia/metabolism ; Polycomb Repressive Complex 2/*metabolism ; Retina/metabolism/physiology ; Stem Cells/cytology/metabolism ; }, abstract = {Polycomb repressive complexes maintain transcriptional repression of genes encoding crucial developmental regulators through chromatin modification. Here we investigated the role of Polycomb repressive complex 2 (PRC2) in retinal development by inactivating its key components Eed and Ezh2. Conditional deletion of Ezh2 resulted in a partial loss of PRC2 function and accelerated differentiation of Müller glial cells. In contrast, inactivation of Eed led to the ablation of PRC2 function at early postnatal stage. Cell proliferation was reduced and retinal progenitor cells were significantly decreased in this mutant, which subsequently caused depletion of Müller glia, bipolar, and rod photoreceptor cells, primarily generated from postnatal retinal progenitor cells. Interestingly, the proportion of amacrine cells was dramatically increased at postnatal stages in the Eed-deficient retina. In accordance, multiple transcription factors controlling amacrine cell differentiation were upregulated. Furthermore, ChIP-seq analysis showed that these deregulated genes contained bivalent chromatin (H3K27me3+ H3K4me3+). Our results suggest that PRC2 is required for proliferation in order to maintain the retinal progenitor cells at postnatal stages and for retinal differentiation by controlling amacrine cell generation.}, } @article {pmid29137924, year = {2018}, author = {Sugahara, S and Fujimoto, T and Kondoh, H and Uchikawa, M}, title = {Nasal and otic placode specific regulation of Sox2 involves both activation by Sox-Sall4 synergism and multiple repression mechanisms.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {61-74}, doi = {10.1016/j.ydbio.2017.11.005}, pmid = {29137924}, issn = {1095-564X}, mesh = {Animals ; Chick Embryo ; Chickens/genetics ; DNA-Binding Proteins/genetics/metabolism ; Enhancer Elements, Genetic ; Gene Expression Regulation, Developmental ; Gene Regulatory Networks ; Neural Crest/metabolism ; Neurons ; Regulatory Elements, Transcriptional ; Repression, Psychology ; SOXB1 Transcription Factors/*metabolism/physiology ; Transcription Factors/genetics/metabolism ; }, abstract = {Transcription factor gene Sox2 is expressed throughout sensory development, but the enhancers that regulate the gene vary depending on the developmental stages and tissues. To gain new insights into the gene regulatory network in sensory placode specification, regulation of the nasal-otic bispecific NOP1 enhancer of Sox2 was investigated in chicken embryos. Deletion and mutational analyses using electroporation showed that transcriptional repression mechanisms in combination with activation mechanisms determine placodal specificity. Activation of the NOP1 enhancer involves synergistic action by Sall4 and SoxB1/SoxE factors that bind to the adjacent sites. Deletion of repressive elements resulted in widening of the tissue area for enhancer activity to a region where the expression of Sall4 and SoxB1/E overlaps, e.g., the CNS and neural crest. Among multiple repressive elements that contribute to the placodal confinement of the NOP1 enhancer activity, CACCT/CACCTG motifs bound by Zeb/Snail family repressors play important roles. Overexpression of δEF1 (Zeb1) or Snail2 (Slug) strongly inhibited NOP1 activity. These data indicate that both activation by Sall4-Sox synergism and multiple repression mechanisms involving Zeb/Snail factors are essential for Sox2 regulation to be confined to the nasal and otic placodes.}, } @article {pmid29137849, year = {2018}, author = {Kleinman, K}, title = {Genera, evolution, and botanists in 1940: Edgar Anderson's "Survey of Modern Opinion".}, journal = {Studies in history and philosophy of biological and biomedical sciences}, volume = {67}, number = {}, pages = {1-7}, doi = {10.1016/j.shpsc.2017.11.001}, pmid = {29137849}, issn = {1879-2499}, mesh = {*Biological Evolution ; Botany/*history ; Cell Biology/history ; Classification/*methods ; Genetics/history ; History, 20th Century ; Missouri ; Plants/*classification/genetics ; }, } @article {pmid29136211, year = {2018}, author = {Höhna, S and Coghill, LM and Mount, GG and Thomson, RC and Brown, JM}, title = {P3: Phylogenetic Posterior Prediction in RevBayes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {4}, pages = {1028-1034}, doi = {10.1093/molbev/msx286}, pmid = {29136211}, issn = {1537-1719}, abstract = {Tests of absolute model fit are crucial in model-based inference because poorly structured models can lead to biased parameter estimates. In Bayesian inference, posterior predictive simulations can be used to test absolute model fit. However, such tests have not been commonly practiced in phylogenetic inference due to a lack of convenient and flexible software. Here, we describe our newly implemented tests of model fit using posterior predictive testing, based on both data- and inference-based test statistics, in the phylogenetics software RevBayes. This new implementation makes a large spectrum of models available for use through a user-friendly and flexible interface.}, } @article {pmid29136184, year = {2018}, author = {Todd, EV and Liu, H and Lamm, MS and Thomas, JT and Rutherford, K and Thompson, KC and Godwin, JR and Gemmell, NJ}, title = {Female Mimicry by Sneaker Males Has a Transcriptomic Signature in Both the Brain and the Gonad in a Sex-Changing Fish.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {225-241}, doi = {10.1093/molbev/msx293}, pmid = {29136184}, issn = {1537-1719}, abstract = {Phenotypic plasticity represents an elegant adaptive response of individuals to a change in their environment. Bluehead wrasses (Thalassoma bifasciatum) exhibit astonishing sexual plasticity, including female-to-male sex change and discrete male morphs that differ strikingly in behavior, morphology, and gonadal investment. Using RNA-seq transcriptome profiling, we examined the genes and physiological pathways underlying flexible behavioral and gonadal differences among female, dominant (bourgeois) male, and female-mimic (sneaker) male blueheads. For the first time in any organism, we find that female mimicry by sneaker males has a transcriptional signature in both the brain and the gonad. Sneaker males shared striking similarity in neural gene expression with females, supporting the idea that males with alternative reproductive phenotypes have "female-like brains." Sneaker males also overexpressed neuroplasticity genes, suggesting that their opportunistic reproductive strategy requires a heightened capacity for neuroplasticity. Bourgeois males overexpressed genes associated with socio-sexual behaviors (e.g., isotocin), but also neuroprotective genes and biomarkers of oxidative stress and aging, indicating a hitherto unexplored cost to these males of attaining the reproductively privileged position at the top of the social hierarchy. Our novel comparison of testicular transcriptomes in a fish with male sexual polymorphism associates greater gonadal investment by sneaker males with overexpression of genes involved in cell proliferation and sperm quality control. We propose that morphological female-mimicry by sneaker male teleosts entails pervasive downregulation of androgenesis genes, consistent with low androgen production in males lacking well-developed secondary sexual characters.}, } @article {pmid29134941, year = {2018}, author = {Guo, LY and Ling, SK and Li, CM and Chen, GJ and Du, ZJ}, title = {Bacillus marinisedimentorum sp. nov., isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {198-203}, doi = {10.1099/ijsem.0.002482}, pmid = {29134941}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Geologic Sediments/*microbiology ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A novel Gram-stain-positive, motile and facultatively anaerobic strain, designated NC2-31T, was isolated from sediment from the coast of Weihai, PR China. Optimal growth occurred at 37 °C, pH 7.5 and with 2.0-3.0 % (w/v) NaCl. MK-7 was the major respiratory quinone. Meso-diaminopimelic acid was a diagnostic diamino acid in the peptidoglycan. The major polar lipids of NC2-31T were diphosphatidylglycerol (DPG), phosphatidylglycerol (PG) and phosphatidylethanolamine (PE). The genomic DNA G+C content of the strain was 46.3 mol%. The predominant cellular fatty acids (>10.0 %) of NC2-31T were iso-C15 : 0 (18.9 %), anteiso-C15 : 0 (15.8 %), summed feature 3 (C16 : 1ω7c and/or iso-C15 : 0 2-OH) (15.3 %) and iso-C16 : 0 (10.3 %). Phylogenetic analysis based on 16S rRNA gene sequences revealed that NC2-31T should be classified as representing a member of the genus Bacillus. Based on data from the current polyphasic study, NC2-31T represents a novel species within the genus Bacillus, for which the name Bacillusmarinisedimentorum sp. nov. is proposed with type strain NC2-31T (=KCTC 33721T=MCCC 1K01239T).}, } @article {pmid29134937, year = {2018}, author = {Miyazaki, A and Shigaki, T and Koinuma, H and Iwabuchi, N and Rauka, GB and Kembu, A and Saul, J and Watanabe, K and Nijo, T and Maejima, K and Yamaji, Y and Namba, S}, title = {'Candidatus Phytoplasma noviguineense', a novel taxon associated with Bogia coconut syndrome and banana wilt disease on the island of New Guinea.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {170-175}, doi = {10.1099/ijsem.0.002480}, pmid = {29134937}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cocos/*microbiology ; DNA, Bacterial/genetics ; Islands ; Musa/*microbiology ; New Guinea ; *Phylogeny ; Phytoplasma/*classification/genetics/isolation & purification ; Plant Diseases/*microbiology ; Polymorphism, Restriction Fragment Length ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Bogia coconut syndrome (BCS) is one of the lethal yellowing (LY)-type diseases associated with phytoplasma presence that are seriously threatening coconut cultivation worldwide. It has recently emerged, and is rapidly spreading in northern parts of the island of New Guinea. BCS-associated phytoplasmas collected in different regions were compared in terms of 16S rRNA gene sequences, revealing high identity among them represented by strain BCS-BoR. Comparative analysis of the 16S rRNA gene sequences revealed that BCS-BoR shared less than a 97.5 % similarity with other species of 'Candidatus Phytoplasma', with a maximum value of 96.08 % (with strain LY; GenBank accession no. U18747). This result indicates the necessity and propriety of a novel taxon for BCS phytoplasmas according to the recommendations of the IRPCM. Phylogenetic analysis was also conducted on 16S rRNA gene sequences, resulting in a monophyletic cluster composed of BCS-BoR and other LY-associated phytoplasmas. Other phytoplasmas on the island of New Guinea associated with banana wilt and arecanut yellow leaf diseases showed high similarities to BCS-BoR and were closely related to BCS phytoplasmas. Based on the uniqueness of their 16S rRNA gene sequences, a novel taxon 'Ca.Phytoplasma noviguineense' is proposed for these phytoplasmas found on the island of New Guinea, with strain BCS-BoR (GenBank accession no. LC228755) as the reference strain. The novel taxon is described in detail, including information on the symptoms of associated diseases and additional genetic features of the secY gene and rp operon.}, } @article {pmid29134936, year = {2018}, author = {Ashraf, S and Soudi, MR and Amoozegar, MA and Moshtaghi Nikou, M and Spröer, C}, title = {Paenibacillus xanthanilyticus sp. nov., a xanthan-degrading bacterium isolated from soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {76-80}, doi = {10.1099/ijsem.0.002453}, pmid = {29134936}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Iran ; Nucleic Acid Hybridization ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Polysaccharides, Bacterial/*metabolism ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A xanthan-degrading bacterium, strain AS7T, was isolated from soil and its taxonomic position was determined using a polyphasic approach. Strain AS7T was a Gram-stain-variable, spore-forming, motile, aerobic, rod-shaped bacterium. Phylogenetic analysis based on 16S rRNA gene sequence analysis revealed that strain AS7T belongs to the genus Paenibacillus, sharing the highest level of sequence similarity with Paenibacillus phyllosphaerae PALXIL04T (98.0 %). The cell-wall peptidoglycan contained meso-diaminopimelic acid. MK-7 was the dominant isoprenoid quinone and the major fatty acid was anteiso-C15 : 0. Polar lipids consisted of diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and two unknown phospholipids. These chemotaxonomic characteristics were consistent with the isolate belonging to the genus Paenibacillus. The G+C content of the genomic DNA was 51.0 mol% and the DNA-DNA hybridization value between strain AS7T and P. phyllosphaerae PALXIL04T was only 14.4±2.5 %. On the basis of phylogenetic analyses, phenotypic and chemotaxonomic characteristics, and DNA-DNA relatedness value, strain AS7T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus xanthanilyticus sp. nov. is proposed. The type strain is AS7T (=IBRC M 10987T=LMG 29451T).}, } @article {pmid29134934, year = {2018}, author = {Yang, YJ and Zhang, YT and Chen, GQ and Cheng, D and Qiu, JG and He, Q and He, J}, title = {Paenibacillus shunpengii sp. nov., isolated from farmland soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {211-216}, doi = {10.1099/ijsem.0.002484}, pmid = {29134934}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; *Farms ; Fatty Acids/chemistry ; Paenibacillus/*classification/genetics/isolation & purification ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A bacterial strain designated YYJ7-1T was isolated from farmland soil in China and characterized using a polyphasic taxonomic approach. Cells of strain YYJ7-1T were Gram-staining-positive, aerobic or facultatively anaerobic, rod-shaped, motile and endospore-forming. Growth occurred at 18-42 °C (optimum at 35 °C), at pH 6.0-8.0 (optimum at pH 7.5) and with 0.0-4.0 % NaCl (optimum with 0.5 %). Phylogenetic analysis based on 16S rRNA gene sequences showed that the strain belonged to the genus Paenibacillus and showed high levels of sequence similarity with respect to Paenibacillus provencensis 4401170T (98.6 %) and Paenibacillus urinalis 5402403T (98.4 %), while lower 16S rRNA gene sequence similarities were observed with all other type strains (97.0 %). However, strain YYJ7-1T showed low DNA-DNA relatedness with P. provencensis 4401170T 48.7±4.5 % (43.6±7.1 % in a reciprocal experiment), and P. urinalis 5402403T 38.9±5.7 % (35.6±6.8 %). The major cellular fatty acids (>10.0 %) of strain YYJ7-1T were anteiso-C15 : 0, iso-C16 : 0 and anteiso-C17 : 0. The polar lipid profile consisted of phospholipids, diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. The major isoprenoid quinone was MK-7. The DNA G+C content was 39.4 mol%. Based on these results, it is concluded that strain YYJ7-1T represents a novel species of the genus Paenibacillus, for which the name Paenibacillus shunpengii sp. nov. is proposed, with YYJ7-1T (=ACCC 19965T=KCTC 33849T) as the type strain.}, } @article {pmid29134931, year = {2018}, author = {Li, W and Zhao, J and Shi, L and Wang, J and Wang, H and Wang, X and Xiang, W}, title = {Glycomyces rhizosphaerae sp. nov., isolated from the root and rhizosphere soil of wheat (Triticum aestivum L.).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {223-227}, doi = {10.1099/ijsem.0.002488}, pmid = {29134931}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Nucleic Acid Hybridization ; *Phylogeny ; Plant Roots/microbiology ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Triticum/*microbiology ; }, abstract = {Two actinomycete strains, NEAU-C11T and NEAU-C8, isolated from rhizosphere soil and wheat root, respectively, collected from Langfang, Hebei Province, China. A polyphasic study was carried out to establish the taxonomic position of the two strains. Morphological and chemotaxonomic characteristics of the isolates coincided with the genus Glycomyces. Sequences analysis of the 16S rRNA gene also showed that the organisms belong to the genus Glycomyces and Glycomyces algeriensis is the highest sequence match for both strains. Furthermore, a combination of DNA-DNA hybridization results and some differential physiological and biochemical properties indicated that they were distinguishable from the phylogenetically closest relatives. Therefore, the two strains represent a novel species, for which the name Glycomycesrhizosphaerae sp. nov. is proposed. The type strain is NEAU-C11T (=CGMCC 4.7396T=DSM 104646T).}, } @article {pmid29134929, year = {2018}, author = {Lee, SY and Siddiqi, MZ and Kim, SY and Yu, HS and Lee, JH and Im, WT}, title = {Mucilaginibacter panaciglaebae sp. nov., isolated from soil of a ginseng field.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {149-154}, doi = {10.1099/ijsem.0.002473}, pmid = {29134929}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Bacteroidetes/*classification/genetics/isolation & purification ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Panax/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-reaction-negative, strictly aerobic, non-motile and rod-shaped bacterium, designated strain BXN5-31T, was isolated from soil of a ginseng field, and its taxonomic position was investigated using a polyphasic approach. Strain BXN5-31T grew at 18-37 °C and at pH 6.0-8.0 on R2A medium. Based on 16S rRNA gene sequence similarity, strain BXN5-31T was shown to belong to the genus Mucilaginibacter and was closely related to Mucilaginibactersoyangensis HME6664T, Mucilaginibacterximonensis XM-003T and Mucilaginibacterpuniceus WS71T. The DNA G+C content was 43.6 %. The predominant respiratory quinone was menaquinone 7 (MK-7) and the major fatty acids were iso-C15 : 0, iso-C17 : 0 3-OH and summed feature 3 (comprising C16 : 1ω6c and/or C16 : 1ω7c). The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The DNA-DNA hybridization values between strain BXN5-31T and three reference strains (M. soyangensis HME6664T, M. ximonensis XM-003T and M. puniceus WS71T) were 9.4±1.9, 8.2±1.3 and 5.7±0.7 %, respectively. The DNA G+C content and chemotaxonomic data supported the affiliation of strain BXN5-31T to the genus Mucilaginibacter. Moreover, the physiological and biochemical results and low level of DNA-DNA relatedness allowed the phenotypic and genotypic differentiation of strain BXN5-31T from recognized species of the genus Mucilaginibacter. The isolate therefore represents a novel species, for which the name Mucilaginibacter panaciglaebae sp. nov. is proposed. The type strain is BXN5-31T (=KACC 14957T=JCM 17085T).}, } @article {pmid29134788, year = {2018}, author = {Wos, G and Willi, Y}, title = {Thermal acclimation in Arabidopsis lyrata: genotypic costs and transcriptional changes.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {123-135}, doi = {10.1111/jeb.13208}, pmid = {29134788}, issn = {1420-9101}, mesh = {Acclimatization/*genetics ; Arabidopsis/*genetics ; *Cold Temperature ; Gene Expression Profiling ; Gene Expression Regulation, Plant/*physiology ; Genes, Plant/genetics ; Genotype ; *Hot Temperature ; Plant Leaves/genetics ; Stress, Physiological/genetics ; }, abstract = {Frost and heat events can be challenging for sessile organisms that cannot escape thermal extremes. However, adverse effects of thermal stress on fitness may be reduced by pre-exposure to cold or heat, a process known as acclimation. To understand the ecological and evolutionary implications of acclimation, we investigated (1) the reduction in performance due to stress pre-exposure, (2) the magnitude of increased leaf resistance to subsequent stress, (3) the costs of acclimation and (4) the genes differing in expression due to stress pre-exposure. Plants of Arabidopsis lyrata were raised under three treatments of pre-exposure: bouts of frost, bouts of heat or constant temperature. Resistance of leaves to subsequent frost and heat stress was then measured by electrolyte leakage. RNA-seq analysis was performed to examine the genes differentially expressed between stress-pre-exposed and control plants. Pre-exposure to stress during growth decreased plant size and increased leaf resistance to subsequent stress independent of whether pre-exposure was to frost or heat. But the highest increase in leaf resistance to frost was found after pre-exposure to frost (as a trend) and in leaf resistance to heat after pre-exposure to heat. No evidence for costs of acclimation was detected. RNA-sequencing suggested that acclimation by frost and heat pre-exposure was caused by distinct mechanisms: modification of the chloroplast membrane and modification of the cell wall and membrane, respectively. Our results suggest that thermal resistance is a labile complex of traits, strongly affected by the previously experienced stress environment, with undetermined costs.}, } @article {pmid29134739, year = {2018}, author = {Tucić, B and Budečević, S and Manitašević Jovanović, S and Vuleta, A and Klingenberg, CP}, title = {Phenotypic plasticity in response to environmental heterogeneity contributes to fluctuating asymmetry in plants: first empirical evidence.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {197-210}, doi = {10.1111/jeb.13207}, pmid = {29134739}, issn = {1420-9101}, abstract = {Fluctuating asymmetry (FA) is widely used to quantify developmental instability (DI) in ecological and evolutionary studies. It has long been recognized that FA may not exclusively originate from DI for sessile organisms such as plants, because phenotypic plasticity in response to heterogeneities in the environment might also produce FA. This study provides the first empirical evidence for this hypothesis. We reasoned that solar irradiance, which is greater on the southern side than on the northern side of plants growing in the temperate zone of the Northern Hemisphere, would cause systematic morphological differences and asymmetry associated with the orientation of plant parts. We used geometric morphometrics to characterize the size and shape of flower parts in Iris pumila grown in a common garden. The size of floral organs was not significantly affected by orientation. Shape and particularly its asymmetric component differed significantly according to orientation for three different floral parts. Orientation accounted for 10.4% of the total shape asymmetry within flowers in the falls, for 11.4% in the standards and for 2.2% in the style branches. This indicates that phenotypic plasticity in response to a directed environmental factor, most likely solar irradiance, contributes to FA of flowers under natural conditions. That FA partly results from phenotypic plasticity and not just from DI needs to be considered by studies of FA in plants and other sessile organisms.}, } @article {pmid29134726, year = {2018}, author = {Voillemot, M and Rougemont, Q and Roux, C and Pannell, JR}, title = {The divergence history of the perennial plant Linaria cavanillesii confirms a recent loss of self-incompatibility.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {136-147}, doi = {10.1111/jeb.13209}, pmid = {29134726}, issn = {1420-9101}, mesh = {Biological Evolution ; Linaria/*classification/*genetics ; *Models, Genetic ; Plant Breeding ; Self-Incompatibility in Flowering Plants/*genetics ; }, abstract = {Many angiosperms prevent inbreeding through a self-incompatibility (SI) system, but the loss of SI has been frequent in their evolutionary history. The loss of SI may often lead to an increase in the selfing rate, with the purging of inbreeding depression and the ultimate evolution of a selfing syndrome, where plants have smaller flowers with reduced pollen and nectar production. In this study, we used approximate Bayesian computation (ABC) to estimate the timing of divergence between populations of the plant Linaria cavanillesii that differ in SI status and in which SI is associated with low inbreeding depression but not with a transition to full selfing or a selfing syndrome. Our analysis suggests that the mixed-mating self-compatible (SC) population may have begun to diverge from the SI populations around 2810 generation ago, a period perhaps too short for the evolution of a selfing syndrome. We conjecture that the SC population of L. cavanillesii is at an intermediate stage of transition between outcrossing and selfing.}, } @article {pmid29134631, year = {2018}, author = {Xu, S and Van Dyken, JD}, title = {Microbial expansion-collision dynamics promote cooperation and coexistence on surfaces.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {153-169}, doi = {10.1111/evo.13393}, pmid = {29134631}, issn = {1558-5646}, abstract = {Microbes colonizing a surface often experience colony growth dynamics characterized by an initial phase of spatial clonal expansion followed by collision between neighboring colonies to form potentially genetically heterogeneous boundaries. For species with life cycles consisting of repeated surface colonization and dispersal, these spatially explicit "expansion-collision dynamics" generate periodic transitions between two distinct selective regimes, "expansion competition" and "boundary competition," each one favoring a different growth strategy. We hypothesized that this dynamic could promote stable coexistence of expansion- and boundary-competition specialists by generating time-varying, negative frequency-dependent selection that insulates both types from extinction. We tested this experimentally in budding yeast by competing an exoenzyme secreting "cooperator" strain (expansion-competition specialists) against nonsecreting "defectors" (boundary-competition specialists). As predicted, we observed cooperator-defector coexistence or cooperator dominance with expansion-collision dynamics, but only defector dominance otherwise. Also as predicted, the steady-state frequency of cooperators was determined by colonization density (the average initial cell-cell distance) and cost of cooperation. Lattice-based spatial simulations give good qualitative agreement with experiments, supporting our hypothesis that expansion-collision dynamics with costly public goods production is sufficient to generate stable cooperator-defector coexistence. This mechanism may be important for maintaining public-goods cooperation and conflict in microbial pioneer species living on surfaces.}, } @article {pmid29134627, year = {2018}, author = {Orbach, DN and Hedrick, B and Würsig, B and Mesnick, SL and Brennan, PLR}, title = {The evolution of genital shape variation in female cetaceans.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {261-273}, doi = {10.1111/evo.13395}, pmid = {29134627}, issn = {1558-5646}, abstract = {Male genital diversification is likely the result of sexual selection. Female genital diversification may also result from sexual selection, although it is less well studied and understood. Female genitalia are complex among whales, dolphins, and porpoises, especially compared to other vertebrates. The evolutionary factors affecting the diversity of vaginal complexity could include ontogeny, allometry, phylogeny, sexual selection, and natural selection. We quantified shape variation in female genitalia using 2D geometric morphometric analysis, and validated the application of this method to study soft tissues. We explored patterns of variation in the shape of the cervix and vagina of 24 cetacean species (n = 61 specimens), and found that genital shape varies primarily in the relative vaginal length and overall aspect ratio of the reproductive tract. Extensive genital shape variation was partly explained by ontogenetic changes and evolutionary allometry among sexually mature cetaceans, whereas phylogenetic signal, relative testis size, and neonate size were not significantly associated with genital shape. Female genital shape is diverse and evolves rapidly even among closely related species, consistent with predictions of sexual selection models and with findings in invertebrate and vertebrate taxa. Future research exploring genital shape variation in 3D will offer new insights into evolutionary mechanisms because internal vaginal structures are variable and can form complex spirals.}, } @article {pmid29134623, year = {2018}, author = {Hanschen, ER and Herron, MD and Wiens, JJ and Nozaki, H and Michod, RE}, title = {Repeated evolution and reversibility of self-fertilization in the volvocine green algae.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {2}, pages = {386-398}, pmid = {29134623}, issn = {1558-5646}, support = {T32 GM084905/GM/NIGMS NIH HHS/United States ; }, abstract = {Outcrossing and self-fertilization are fundamental strategies of sexual reproduction, each with different evolutionary costs and benefits. Self-fertilization is thought to be an evolutionary "dead-end" strategy, beneficial in the short term but costly in the long term, resulting in self-fertilizing species that occupy only the tips of phylogenetic trees. Here, we use volvocine green algae to investigate the evolution of self-fertilization. We use ancestral-state reconstructions to show that self-fertilization has repeatedly evolved from outcrossing ancestors and that multiple reversals from selfing to outcrossing have occurred. We use three phylogenetic metrics to show that self-fertilization is not restricted to the tips of the phylogenetic tree, a finding inconsistent with the view of self-fertilization as a dead-end strategy. We also find no evidence for higher extinction rates or lower speciation rates in selfing lineages. We find that self-fertilizing species have significantly larger colonies than outcrossing species, suggesting the benefits of selfing may counteract the costs of increased size. We speculate that our macroevolutionary results on self-fertilization (i.e., non-tippy distribution, no decreased diversification rates) may be explained by the haploid-dominant life cycle that occurs in volvocine algae, which may alter the costs and benefits of selfing.}, } @article {pmid29134265, year = {2018}, author = {Fu, J and Zong, G and Zhang, P and Gu, Y and Cao, G}, title = {Deletion of the β-Propeller Protein Gene Rv1057 Reduces ESAT-6 Secretion and Intracellular Growth of Mycobacterium tuberculosis.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {401-409}, pmid = {29134265}, issn = {1432-0991}, support = {81471921//the National Natural Science Foundation of China/ ; 201604//the Innovation Project of the Shandong Academy of Medical Sciences/ ; }, mesh = {Antigens, Bacterial/*genetics/metabolism ; Bacterial Proteins/*genetics/metabolism ; Cells, Cultured ; Gene Deletion ; Humans ; Interleukin-10/genetics/metabolism ; Interleukin-4/genetics/metabolism ; Macrophages/metabolism/microbiology ; Mycobacterium tuberculosis/*genetics/*growth & development/metabolism ; Nitric Oxide/metabolism ; Tuberculosis/genetics/metabolism/*microbiology ; Virulence Factors/genetics/metabolism ; }, abstract = {Rv1057 is the only β-propeller protein in Mycobacterium tuberculosis, but its biological function is still unclear. In this study, we generated a deletion mutant of Rv1057 (D1057) in the virulent M. tuberculosis strain H37Rv and examined the characteristics of the mutant in vitro and in macrophages. We found that deletion of Rv1057 reduces secretion of the major virulence factor ESAT-6 and ESAT-6 stops in the cell envelope fraction during secretion, although ESAT-6 levels were similar in lysates of the mutant and control strains. In infected macrophages, Rv1057 deletion significantly reduced the secretion levels of cytokines IL-1β, IL-10, TNF-α, and INF-γ, but did not affect IL-4 and IL-8. D1057-infected macrophages also release less LDH and produce more nitric oxide (NO) than H37Rv- and D1057com (Rv1057 complemented strain of D1057com)-infected macrophages, indicating that D1057 has the decreased cytotoxicity compared to H37Rv or D1057com. In addition, the capacity of the Rv1057 deletion mutant to grow in macrophages was significantly lower than that of H37Rv and D1057com. Our findings support a role for Rv1057 in ESAT-6 secretion and in modulating the interactions between M. tuberculosis and macrophages.}, } @article {pmid29133900, year = {2018}, author = {Courchamp, F and Bradshaw, CJA}, title = {100 articles every ecologist should read.}, journal = {Nature ecology & evolution}, volume = {2}, number = {2}, pages = {395-401}, doi = {10.1038/s41559-017-0370-9}, pmid = {29133900}, issn = {2397-334X}, abstract = {Reading scientific articles is a valuable and major part of the activity of scientists. Yet, with the upsurge of currently available articles and the increasing specialization of scientists, it becomes difficult to identify, let alone read, important papers covering topics not directly related to one's own specific field of research, or that are older than a few years. Our objective was to propose a list of seminal papers deemed to be of major importance in ecology, thus providing a general 'must-read' list for any new ecologist, regardless of particular topic or expertise. We generated a list of 544 papers proposed by 147 ecology experts (journal editorial members) and subsequently ranked via random-sample voting by 368 of 665 contacted ecology experts, covering 6 article types, 6 approaches and 17 fields. Most of the recommended papers were not published in the highest-ranking journals, nor did they have the highest number of mean annual citations. The articles proposed through the collective recommendation of several hundred experienced researchers probably do not represent an 'ultimate', invariant list, but they certainly contain many high-quality articles that are undoubtedly worth reading-regardless of the specific field of interest in ecology-to foster the understanding, knowledge and inspiration of early-career scientists.}, } @article {pmid29133884, year = {2018}, author = {Swidergall, M and Solis, NV and Lionakis, MS and Filler, SG}, title = {EphA2 is an epithelial cell pattern recognition receptor for fungal β-glucans.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {53-61}, pmid = {29133884}, issn = {2058-5276}, support = {K99 DE026856/DE/NIDCR NIH HHS/United States ; R01 AI124566/AI/NIAID NIH HHS/United States ; R01 DE026600/DE/NIDCR NIH HHS/United States ; }, mesh = {Animals ; Candida albicans/growth & development/*metabolism ; Candidiasis, Oral/*metabolism/pathology ; Cell Line ; Cytokines/biosynthesis ; Disease Models, Animal ; Endocytosis ; Epithelial Cells/cytology/metabolism/microbiology ; ErbB Receptors/antagonists & inhibitors/metabolism ; Inflammation Mediators/analysis ; Male ; Mice ; Mice, Inbred C57BL ; Mouth Mucosa/cytology/*metabolism/microbiology ; Phosphorylation ; Receptor, EphA2/antagonists & inhibitors/deficiency/*metabolism ; Receptors, Pattern Recognition/antagonists & inhibitors/deficiency/*metabolism ; STAT3 Transcription Factor/metabolism ; Signal Transduction ; beta-Glucans/*metabolism ; }, abstract = {Oral epithelial cells discriminate between pathogenic and non-pathogenic stimuli, and only induce an inflammatory response when they are exposed to high levels of a potentially harmful microorganism. The pattern recognition receptors (PRRs) in epithelial cells that mediate this differential response are poorly understood. Here, we demonstrate that the ephrin type-A receptor 2 (EphA2) is an oral epithelial cell PRR that binds to exposed β-glucans on the surface of the fungal pathogen Candida albicans. Binding of C. albicans to EphA2 on oral epithelial cells activates signal transducer and activator of transcription 3 and mitogen-activated protein kinase signalling in an inoculum-dependent manner, and is required for induction of a proinflammatory and antifungal response. EphA2 -/- mice have impaired inflammatory responses and reduced interleukin-17 signalling during oropharyngeal candidiasis, resulting in more severe disease. Our study reveals that EphA2 functions as a PRR for β-glucans that senses epithelial cell fungal burden and is required for the maximal mucosal inflammatory response to C. albicans.}, } @article {pmid29133883, year = {2018}, author = {Harvey, H and Bondy-Denomy, J and Marquis, H and Sztanko, KM and Davidson, AR and Burrows, LL}, title = {Pseudomonas aeruginosa defends against phages through type IV pilus glycosylation.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {47-52}, doi = {10.1038/s41564-017-0061-y}, pmid = {29133883}, issn = {2058-5276}, mesh = {Arabinose/analogs & derivatives/metabolism ; Bacterial Proteins/genetics/*metabolism ; Fimbriae Proteins/genetics/*metabolism ; Fimbriae, Bacterial/*metabolism ; Glycosylation ; Host Specificity ; Models, Molecular ; Mutation ; Pseudomonas Phages/genetics/*physiology ; Pseudomonas aeruginosa/genetics/*metabolism/ultrastructure/*virology ; Viral Tail Proteins/genetics ; }, abstract = {Since phages present a major challenge to survival in most environments, bacteria express a battery of anti-phage defences including CRISPR-Cas, restriction-modification and abortive infection systems 1-4 . Such strategies are effective, but the phage genome-which encodes potentially inhibitory gene products-is still allowed to enter the cell. The safest way to preclude phage infection is to block initial phage adsorption to the cell. Here, we describe a cell-surface modification that blocks infection by certain phages. Strains of the opportunistic pathogen Pseudomonas aeruginosa express one of five different type IV pilins (T4P) 5 , two of which are glycosylated with O-antigen units 6 or polymers of D-arabinofuranose 7-9 . We propose that predation by bacteriophages that use T4P as receptors selects for strains that mask potential phage binding sites using glycosylation. Here, we show that both modifications protect P. aeruginosa from certain pilus-specific phages. Alterations to pilin sequence can also block phage infection, but glycosylation is considered less likely to create disadvantageous phenotypes. Through construction of chimeric phages, we show that specific phage tail proteins allow for infection of strains with glycosylated pili. These studies provide insight into first-line bacterial defences against predation and ways in which phages circumvent them, and provide a rationale for the prevalence of pilus glycosylation in nature.}, } @article {pmid29133882, year = {2018}, author = {Yutin, N and Makarova, KS and Gussow, AB and Krupovic, M and Segall, A and Edwards, RA and Koonin, EV}, title = {Discovery of an expansive bacteriophage family that includes the most abundant viruses from the human gut.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {38-46}, pmid = {29133882}, issn = {2058-5276}, support = {Z01 LM000073-12/NULL/Intramural NIH HHS/United States ; }, mesh = {Bacteriophages/*classification/*genetics ; Bacteroidetes/virology ; Databases, Protein ; Gastrointestinal Microbiome/*genetics ; Genome, Viral/genetics ; *Genomics ; Humans ; *Metagenomics ; Models, Genetic ; Molecular Sequence Data ; Phylogeny ; Sequence Analysis, Protein ; Viral Proteins/chemistry/genetics ; }, abstract = {Metagenomic sequence analysis is rapidly becoming the primary source of virus discovery 1-3 . A substantial majority of the currently available virus genomes come from metagenomics, and some of these represent extremely abundant viruses, even if never grown in the laboratory. A particularly striking case of a virus discovered via metagenomics is crAssphage, which is by far the most abundant human-associated virus known, comprising up to 90% of sequences in the gut virome 4 . Over 80% of the predicted proteins encoded in the approximately 100 kilobase crAssphage genome showed no significant similarity to available protein sequences, precluding classification of this virus and hampering further study. Here we combine a comprehensive search of genomic and metagenomic databases with sensitive methods for protein sequence analysis to identify an expansive, diverse group of bacteriophages related to crAssphage and predict the functions of the majority of phage proteins, in particular those that comprise the structural, replication and expression modules. Most, if not all, of the crAss-like phages appear to be associated with diverse bacteria from the phylum Bacteroidetes, which includes some of the most abundant bacteria in the human gut microbiome and that are also common in various other habitats. These findings provide for experimental characterization of the most abundant but poorly understood members of the human-associated virome.}, } @article {pmid29133184, year = {2018}, author = {Bushnell, HL and Feiler, CE and Ketosugbo, KF and Hellerman, MB and Nazzaro, VL and Johnson, RI}, title = {JNK is antagonized to ensure the correct number of interommatidial cells pattern the Drosophila retina.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {94-107}, pmid = {29133184}, issn = {1095-564X}, support = {R15 GM114729/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Apoptosis/physiology ; Body Patterning/physiology ; Drosophila Proteins/metabolism ; Drosophila melanogaster/enzymology/genetics/metabolism ; Epithelium/enzymology/metabolism ; Gene Expression Regulation, Developmental/genetics ; JNK Mitogen-Activated Protein Kinases/*antagonists & inhibitors/metabolism ; Microfilament Proteins/metabolism ; Morphogenesis ; Pupa/metabolism ; Retina/cytology/enzymology/metabolism ; Signal Transduction ; }, abstract = {Apoptosis is crucial during the morphogenesis of most organs and tissues, and is utilized for tissues to achieve their proper size, shape and patterning. Many signaling pathways contribute to the precise regulation of apoptosis. Here we show that Jun N-terminal Kinase (JNK) activity contributes to the coordinated removal of interommatidial cells via apoptosis in the Drosophila pupal retina. This is consistent with previous findings that JNK activity promotes apoptosis in other epithelia. However, we found that JNK activity is repressed by Cindr (the CIN85 and CD2AP ortholog) in order to promote cell survival. Reducing the amount of Cindr resulted in ectopic cell death. Increased expression of the Drosophila JNK basket in the setting of reduced cindr expression was found to result in even more severe apoptosis, whilst ectopic death was found to be reduced if retinas were heterozygous for basket. Hence Cindr is required to properly restrict JNK-mediated apoptosis in the pupal eye, resulting in the correct number of interommatidial cells. A lack of precise control over developmental apoptosis can lead to improper tissue morphogenesis.}, } @article {pmid29132819, year = {2018}, author = {Defoirdt, T}, title = {Quorum-Sensing Systems as Targets for Antivirulence Therapy.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {313-328}, doi = {10.1016/j.tim.2017.10.005}, pmid = {29132819}, issn = {1878-4380}, abstract = {The development of novel therapies to control diseases caused by antibiotic-resistant pathogens is one of the major challenges we are currently facing. Many important plant, animal, and human pathogens regulate virulence by quorum sensing, bacterial cell-to-cell communication with small signal molecules. Consequently, a significant research effort is being undertaken to identify and use quorum-sensing-interfering agents in order to control diseases caused by these pathogens. In this review, an overview of our current knowledge of quorum-sensing systems of Gram-negative model pathogens is presented as well as the link with virulence of these pathogens, and recent advances and challenges in the development of quorum-sensing-interfering therapies are discussed.}, } @article {pmid29132776, year = {2018}, author = {Carthey, AJR and Blumstein, DT}, title = {Predicting Predator Recognition in a Changing World.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {2}, pages = {106-115}, doi = {10.1016/j.tree.2017.10.009}, pmid = {29132776}, issn = {1872-8383}, mesh = {Animals ; *Biological Evolution ; *Cues ; *Ecosystem ; Food Chain ; Models, Biological ; *Predatory Behavior ; }, abstract = {Through natural as well as anthropogenic processes, prey can lose historically important predators and gain novel ones. Both predator gain and loss frequently have deleterious consequences. While numerous hypotheses explain the response of individuals to novel and familiar predators, we lack a unifying conceptual model that predicts the fate of prey following the introduction of a novel or a familiar (reintroduced) predator. Using the concept of eco-evolutionary experience, we create a new framework that allows us to predict whether prey will recognize and be able to discriminate predator cues from non-predator cues and, moreover, the likely persistence outcomes for 11 different predator-prey interaction scenarios. This framework generates useful and testable predictions for ecologists, conservation scientists, and decision-makers.}, } @article {pmid29132689, year = {2018}, author = {Shabani, M and Vears, D and Borry, P}, title = {Raw Genomic Data: Storage, Access, and Sharing.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {8-10}, doi = {10.1016/j.tig.2017.10.004}, pmid = {29132689}, issn = {0168-9525}, mesh = {Consent Forms ; Electronic Health Records ; *Genomics/trends ; Humans ; Information Dissemination/*methods ; Information Storage and Retrieval/*methods ; Laboratories ; }, abstract = {Patients are increasingly being encouraged and supported to access and control their own medical and genomic data. We argue that well-established and transparent raw genomic data retention and returning policies are imperative to enable patients to practice their rights to access and control raw data.}, } @article {pmid29131109, year = {2018}, author = {Spoor, JA and Oosterhuis, JW and Hersmus, R and Biermann, K and Wolffenbuttel, KP and Cools, M and Kazmi, Z and Ahmed, SF and Looijenga, LHJ}, title = {Histological Assessment of Gonads in DSD: Relevance for Clinical Management.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {106-122}, doi = {10.1159/000481757}, pmid = {29131109}, issn = {1661-5433}, support = {G1100236//Medical Research Council/United Kingdom ; }, mesh = {Disorders of Sex Development/*pathology/*therapy ; Gonads/embryology/*pathology ; Humans ; Practice Guidelines as Topic ; Risk Factors ; Sex Differentiation ; Telemedicine ; }, abstract = {Malignant gonadal germ cell tumors, referred to as germ cell cancers (GCC), occur with increased frequency in individuals who have specific types of differences (disorders) of sex development (DSD). Recent population-based studies have identified new environmental and genetic risk factors that have led to a 'genvironment' hypothesis, which may potentially be helpful in risk assessment in DSD-related GCC. In DSD, the malignancy risk is highly heterogeneous, but recent studies allow now to discriminate between high- and low-risk conditions. Gonadal biopsy is in some cases the best procedure of choice to assess the risk, and with the availability of immunohistochemical biomarkers [OCT3/4 (POU5F1), TSPY, SOX9, FOXL2 and KITLG (SCF)], a reliable classification of GCC and its precursors can be made. The opportunities in the field of virtual diagnostic pathology will be presented, having possibilities for rare diseases in general and DSD specifically. It is expected that the International DSD Registry will stimulate international collaborations, facilitating better diagnostic procedures as well as research.}, } @article {pmid29131089, year = {2018}, author = {Bertelloni, S and Russo, G and Baroncelli, GI}, title = {Human Chorionic Gonadotropin Test: Old Uncertainties, New Perspectives, and Value in 46,XY Disorders of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {41-49}, doi = {10.1159/000481552}, pmid = {29131089}, issn = {1661-5433}, mesh = {Chorionic Gonadotropin/*analysis ; Clinical Laboratory Techniques/*methods ; Dihydrotestosterone/blood ; Disorder of Sex Development, 46,XY/blood/*diagnosis ; Humans ; Testosterone/blood ; *Uncertainty ; }, abstract = {The human chorionic gonadotropin (hCG) test represents a key step in assessing Leydig cell function in prepubertal males, but differences in terms of hCG doses, number of injections, and sequence of blood drawing are published in the literature, showing poor standardization. The few available data in healthy boys are summarized here. A recombinant hCG (rhCG) formulation might permit overcoming some controversies as well as avoid the potential biological risk related to the injection of extractive hormones. Studies in humans are scarce, but they indicate that 250 µg rhCG in a single dose may represent a useful scheme for the dynamic evaluation of Leydig cell function in children as well as in adults. The main indication for hCG testing in childhood is the investigation of 46,XY disorders of sex differentiation. The test must also be considered in order to investigate the presence of functional testicular tissue when gonadal peptide hormones cannot be measured.}, } @article {pmid29129922, year = {2018}, author = {Teschendorff, AE and Relton, CL}, title = {Statistical and integrative system-level analysis of DNA methylation data.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {3}, pages = {129-147}, pmid = {29129922}, issn = {1471-0064}, support = {MC_UU_12013/2//Medical Research Council/United Kingdom ; }, abstract = {Epigenetics plays a key role in cellular development and function. Alterations to the epigenome are thought to capture and mediate the effects of genetic and environmental risk factors on complex disease. Currently, DNA methylation is the only epigenetic mark that can be measured reliably and genome-wide in large numbers of samples. This Review discusses some of the key statistical challenges and algorithms associated with drawing inferences from DNA methylation data, including cell-type heterogeneity, feature selection, reverse causation and system-level analyses that require integration with other data types such as gene expression, genotype, transcription factor binding and other epigenetic information.}, } @article {pmid29129921, year = {2018}, author = {Gardy, JL and Loman, NJ}, title = {Towards a genomics-informed, real-time, global pathogen surveillance system.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {9-20}, doi = {10.1038/nrg.2017.88}, pmid = {29129921}, issn = {1471-0064}, support = {MR/M501621/1//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Communicable Diseases, Emerging/*epidemiology/etiology/genetics ; Computer Systems ; Environmental Health ; Epidemics ; Genomics ; Hemorrhagic Fever, Ebola/epidemiology ; High-Throughput Nucleotide Sequencing ; Humans ; Metagenomics ; Models, Biological ; Molecular Epidemiology ; Public Health ; Public Health Surveillance/*methods ; }, abstract = {The recent Ebola and Zika epidemics demonstrate the need for the continuous surveillance, rapid diagnosis and real-time tracking of emerging infectious diseases. Fast, affordable sequencing of pathogen genomes - now a staple of the public health microbiology laboratory in well-resourced settings - can affect each of these areas. Coupling genomic diagnostics and epidemiology to innovative digital disease detection platforms raises the possibility of an open, global, digital pathogen surveillance system. When informed by a One Health approach, in which human, animal and environmental health are considered together, such a genomics-based system has profound potential to improve public health in settings lacking robust laboratory capacity.}, } @article {pmid29129920, year = {2018}, author = {Wrighton, KH}, title = {Transcription: Putting R loops firmly on the map.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {5}, pmid = {29129920}, issn = {1471-0064}, } @article {pmid29129919, year = {2018}, author = {Burgess, DJ}, title = {Functional genomics: Shining a light on genetic screen strategies.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {6-7}, pmid = {29129919}, issn = {1471-0064}, } @article {pmid29128373, year = {2018}, author = {Weston, N and Sharma, P and Ricci, V and Piddock, LJV}, title = {Regulation of the AcrAB-TolC efflux pump in Enterobacteriaceae.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {425-431}, doi = {10.1016/j.resmic.2017.10.005}, pmid = {29128373}, issn = {1769-7123}, support = {G0501415//Medical Research Council/United Kingdom ; G0801977//Medical Research Council/United Kingdom ; }, mesh = {Bacterial Proteins/chemistry/genetics/*metabolism ; Carrier Proteins/chemistry/genetics/*metabolism ; Escherichia coli/chemistry/genetics/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Gene Expression Regulation, Bacterial ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; Salmonella enterica/chemistry/genetics/*metabolism ; }, abstract = {Bacterial multidrug efflux systems are a major mechanism of antimicrobial resistance and are fundamental to the physiology of Gram-negative bacteria. The resistance-nodulation-division (RND) family of efflux pumps is the most clinically significant, as it is associated with multidrug resistance. Expression of efflux systems is subject to multiple levels of regulation, involving local and global transcriptional regulation as well as post-transcriptional and post-translational regulation. The best-characterised RND system is AcrAB-TolC, which is present in Enterobacteriaceae. This review describes the current knowledge and new data about the regulation of the acrAB and tolC genes in Escherichia coli and Salmonella enterica.}, } @article {pmid29128264, year = {2018}, author = {Ben-Hamo, O and Rosner, A and Rabinowitz, C and Oren, M and Rinkevich, B}, title = {Coupling astogenic aging in the colonial tunicate Botryllus schlosseri with the stress protein mortalin.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {33-46}, doi = {10.1016/j.ydbio.2017.10.023}, pmid = {29128264}, issn = {1095-564X}, mesh = {Age Factors ; Aging/metabolism ; Animals ; Apoptosis/physiology ; HSP70 Heat-Shock Proteins/*metabolism/physiology ; Heat-Shock Proteins ; Pyridines/metabolism ; Reproduction, Asexual ; Thiazoles/metabolism ; Urochordata/*genetics/*metabolism ; }, abstract = {Botryllus schlosseri, a colonial marine invertebrate, exhibits three generations of short-lived astogenic modules that continuously grow and die throughout the colony's entire lifespan, within week-long repeating budding cycles (blastogenesis), each consisting of four stages (A-D). At stage D, aging is followed by the complete absorption of adult modules (zooids) via a massive apoptotic process. Here we studied in Botryllus the protein mortalin (HSP70s member), a molecule largely known for its association with aging and proliferation. In-situ hybridization and qPCR assays reveal that mortalin follows the cyclic pattern of blastogenesis. Colonies at blastogenic stage D display the highest mortalin levels, and young modules exhibit elevated mortalin levels compared to old modules. Manipulations of mortalin with the specific allosteric inhibitor MKT-077 has led to a decrease in the modules' growth rate and the development of abnormal somatic/germinal morphologies (primarily in vasculature and in organs such as the endostyle, the stomach and gonads). We therefore propose that mortalin plays a significant role in the astogeny and aging of colonial modules in B. schlosseri, by direct involvement in the regulation of blastogenesis.}, } @article {pmid29127550, year = {2018}, author = {Palacios-Pérez, M and Andrade-Díaz, F and José, MV}, title = {A Proposal of the Ur-proteome.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {2}, pages = {245-258}, pmid = {29127550}, issn = {1573-0875}, support = {PAPIIT IN224015//DGAPA-UNAM/ ; Fellowship 694877//CONACYT Mexico/ ; Fellowship 204546//CONACYT Mexico/ ; }, mesh = {Amino Acids/*chemistry ; *Evolution, Molecular ; Genetic Code ; *Origin of Life ; Proteome/*chemistry ; RNA/*chemistry ; }, abstract = {Herein we outline a plausible proteome, encoded by assuming a primeval RNY genetic code. We unveil the primeval phenotype by using only the RNA genotype; it means that we recovered the most ancestral proteome, mostly made of the 8 amino acids encoded by RNY triplets. By looking at those fragments, it is noticeable that they are positioned, not at catalytic sites, but in the cofactor binding sites. It implies that the stabilization of a molecule appeared long before its catalytic activity, and therefore the Ur-proteome comprised a set of proteins modules that corresponded to Cofactor Stabilizing Binding Sites (CSBSs), which we call the primitive bindome. With our method, we reconstructed the structures of the "first protein modules" that Sobolevsky and Trifonov (2006) found by using only RMSD. We also examine the probable cofactors that bound to them. We discuss the notion of CSBSs as the first proteins modules in progenotes in the context of several proposals about the primitive forms of life.}, } @article {pmid29127456, year = {2018}, author = {Kamatani, S and Takegawa, K and Kimura, Y}, title = {Catalytic Activity Profile of Polyphosphate Kinase 1 from Myxococcus xanthus.}, journal = {Current microbiology}, volume = {75}, number = {4}, pages = {379-385}, pmid = {29127456}, issn = {1432-0991}, support = {16K07667//Grants-in-Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan/ ; }, mesh = {Adenosine Diphosphate/metabolism ; Adenosine Triphosphate/metabolism ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biocatalysis ; Kinetics ; Myxococcus xanthus/chemistry/*enzymology/genetics ; Phosphotransferases (Phosphate Group Acceptor)/chemistry/genetics/*metabolism ; }, abstract = {Polyphosphate kinase 1 (Ppk1) catalyzes reverse transfer of the terminal phosphate from ATP to form polyphosphate (polyP) and from polyP to form ATP, and is responsible for the synthesis of most of cellular polyPs. When Ppk1 from Myxococcus xanthus was incubated with 0.2 mM polyP60-70 and 1 mM ATP or ADP, the rate of ATP synthesis was approximately 1.5-fold higher than that of polyP synthesis. If in the same reaction the proportion of ADP in the ATP/ADP mixture exceeded one-third, the equilibrium shifted to ATP synthesis, suggesting that M. xanthus Ppk1 preferentially catalyzed ATP formation. At the same time, GTP and GDP were not recognized as substrates by Ppk1. In the absence of polyP, Ppk1 generated ATP and AMP from ADP, and ADP from ATP and AMP, suggesting that the enzyme catalyzed the transfer of a phosphate group between ADP molecules yielding ATP and AMP, thus exhibiting adenylate kinase activity.}, } @article {pmid29127455, year = {2018}, author = {Huang, B and Gao, S and Xu, Z and He, H and Pan, X}, title = {The Functional Mechanisms and Application of Electron Shuttles in Extracellular Electron Transfer.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {99-106}, pmid = {29127455}, issn = {1432-0991}, support = {41401558//The National Natural Science Foundation of China/ ; }, mesh = {Bacteria/*chemistry/metabolism ; Electron Transport ; Electrons ; Oxidation-Reduction ; }, abstract = {Electron shuttles extensively exist in various environments. Some kinds of organic substances can be applied by microorganisms to produce electrons, and then the electrons can be transferred to other substances or microorganisms through electron shuttles, resulting in coexistence and interaction of diverse species of microbes. In this review, the functional mechanisms of extracellular electron transfer mediated by different electron shuttles are described. And different subtypes as well as the application of electron shuttles in microbial degradation of pollutants, microbial electricity, and the promotion of energy generation are also discussed. Summary results show that extracellular electron transfer is based on the electrogenesis microorganism with the structure of cytochromes or pili. Materials were usually used in long-distance electron transfer because of their widespread presence and abundance. Therefore, the review is beneficial to perceive the pathways of extracellular electron transfer mediated by electron shuttles and explore the contribution of different electron shuttles in extracellular electron transfer.}, } @article {pmid29127454, year = {2018}, author = {Chen, X and Li, QY and Li, GD and Xu, FJ and Han, L and Jiang, Y and Huang, XS and Jiang, CL}, title = {The Distal Gut Bacterial Community of Some Primates and Carnivora.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {213-222}, pmid = {29127454}, issn = {1432-0991}, support = {31270001//National Natural Science Foundation of China/ ; 81573327//National Natural Science Foundation of China/ ; 31460005//National Natural Science Foundation of China (CN)/ ; }, mesh = {Actinobacteria ; Animals ; Archaea/*classification/genetics ; Bacteria/*classification/genetics ; *Carnivora ; Feces/microbiology ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/*microbiology ; High-Throughput Nucleotide Sequencing ; *Primates ; }, abstract = {Huge numbers of bacteria reside in the digestive tract of host and these microorganisms play a vital role in the host health, especially in the digestion of food and the development of immune system. Host phylogeny and diet, especially long-term diet, both have great influence on the gut bacterial community. Other aspects of host, such as gender, age, and the geography and weather they lived, are also correlated to their gut bacterial community. Feces are usually used for gut bacteria study and fecal bacteria can represent the distal gut bacteria. In order to determine the influence of the host phylogeny and diet on the composition of distal gut bacterial community and to interpret bacterial population and diversity in the intestinal of animals, the distal gut bacterial community of four kinds of primates and five kinds of carnivora (including herbivorous, omnivorous, and carnivorous) were investigated using high-throughput sequencing and the isolation of the Actinobacteria from fresh feces of several primates was processed. The results showed the host phylogeny had a greater influence on the distal gut bacterial community of the primates and carnivora than the host diet. A total of 44 bacteria phyla and two archaea phyla were detected, which indicated that the distal gut bacteria of these animals were abundant. The distal gut bacteria were relatively stable and wildly shared in primates and carnivora. The difference in distal gut bacteria of the two animal orders is mainly determined by relative abundance of most distal gut bacteria rather than by the taxa of these bacteria.}, } @article {pmid29126819, year = {2018}, author = {Sokolow, SH and Wood, CL and Jones, IJ and Lafferty, KD and Kuris, AM and Hsieh, MH and De Leo, GA}, title = {To Reduce the Global Burden of Human Schistosomiasis, Use 'Old Fashioned' Snail Control.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {23-40}, pmid = {29126819}, issn = {1471-5007}, support = {R01 TW010286/TW/FIC NIH HHS/United States ; }, mesh = {Animals ; Disease Eradication/*methods ; Humans ; Schistosomiasis/*epidemiology/*prevention & control/transmission ; Snails/parasitology ; }, abstract = {Control strategies to reduce human schistosomiasis have evolved from 'snail picking' campaigns, a century ago, to modern wide-scale human treatment campaigns, or preventive chemotherapy. Unfortunately, despite the rise in preventive chemotherapy campaigns, just as many people suffer from schistosomiasis today as they did 50 years ago. Snail control can complement preventive chemotherapy by reducing the risk of transmission from snails to humans. Here, we present ideas for modernizing and scaling up snail control, including spatiotemporal targeting, environmental diagnostics, better molluscicides, new technologies (e.g., gene drive), and 'outside the box' strategies such as natural enemies, traps, and repellants. We conclude that, to achieve the World Health Assembly's stated goal to eliminate schistosomiasis, it is time to give snail control another look.}, } @article {pmid29126565, year = {2018}, author = {Montoya, JM and Donohue, I and Pimm, SL}, title = {Planetary Boundaries for Biodiversity: Implausible Science, Pernicious Policies.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {2}, pages = {71-73}, doi = {10.1016/j.tree.2017.10.004}, pmid = {29126565}, issn = {1872-8383}, mesh = {*Biodiversity ; *Conservation of Natural Resources ; Ecology/*methods ; Ecosystem ; }, abstract = {The notion of a 'safe operating space for biodiversity' is vague and encourages harmful policies. Attempts to fix it strip it of all meaningful content. Ecology is rapidly gaining insights into the connections between biodiversity and ecosystem stability. We have no option but to understand ecological complexity and act accordingly.}, } @article {pmid29126321, year = {2018}, author = {Banwell, EF and Piette, BMAG and Taormina, A and Heddle, JG}, title = {Reciprocal Nucleopeptides as the Ancestral Darwinian Self-Replicator.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {404-416}, pmid = {29126321}, issn = {1537-1719}, abstract = {Even the simplest organisms are too complex to have spontaneously arisen fully formed, yet precursors to first life must have emerged ab initio from their environment. A watershed event was the appearance of the first entity capable of evolution: the Initial Darwinian Ancestor. Here, we suggest that nucleopeptide reciprocal replicators could have carried out this important role and contend that this is the simplest way to explain extant replication systems in a mathematically consistent way. We propose short nucleic acid templates on which amino-acylated adapters assembled. Spatial localization drives peptide ligation from activated precursors to generate phosphodiester-bond-catalytic peptides. Comprising autocatalytic protein and nucleic acid sequences, this dynamical system links and unifies several previous hypotheses and provides a plausible model for the emergence of DNA and the operational code.}, } @article {pmid29126243, year = {2018}, author = {O'Toole, ÁN and Hurst, LD and McLysaght, A}, title = {Faster Evolving Primate Genes Are More Likely to Duplicate.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {107-118}, pmid = {29126243}, issn = {1537-1719}, support = {669207//European Research Council/International ; }, abstract = {An attractive and long-standing hypothesis regarding the evolution of genes after duplication posits that the duplication event creates new evolutionary possibilities by releasing a copy of the gene from constraint. Apparent support was found in numerous analyses, particularly, the observation of higher rates of evolution in duplicated as compared with singleton genes. Could it, instead, be that more duplicable genes (owing to mutation, fixation, or retention biases) are intrinsically faster evolving? To uncouple the measurement of rates of evolution from the determination of duplicate or singleton status, we measure the rates of evolution in singleton genes in outgroup primate lineages but classify these genes as to whether they have duplicated or not in a crown group of great apes. We find that rates of evolution are higher in duplicable genes prior to the duplication event. In part this is owing to a negative correlation between coding sequence length and rate of evolution, coupled with a bias toward smaller genes being more duplicable. The effect is masked by difference in expression rate between duplicable genes and singletons. Additionally, in contradiction to the classical assumption, we find no convincing evidence for an increase in dN/dS after duplication, nor for rate asymmetry between duplicates. We conclude that high rates of evolution of duplicated genes are not solely a consequence of the duplication event, but are rather a predictor of duplicability. These results are consistent with a model in which successful gene duplication events in mammals are skewed toward events of minimal phenotypic impact.}, } @article {pmid29126241, year = {2018}, author = {Kajala, I and Bergsveinson, J and Friesen, V and Redekop, A and Juvonen, R and Storgårds, E and Ziola, B}, title = {Lactobacillus backii and Pediococcus damnosus isolated from 170-year-old beer recovered from a shipwreck lack the metabolic activities required to grow in modern lager beer.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {1}, pages = {}, doi = {10.1093/femsec/fix152}, pmid = {29126241}, issn = {1574-6941}, abstract = {In 2010, bottles of beer containing viable bacteria of the common beer-spoilage species Lactobacillus backii and Pediococcus damnosus were recovered from a shipwreck near the Åland Islands, Finland. The 170-year quiescent state maintained by the shipwreck bacteria presented a unique opportunity to study lactic acid bacteria (LAB) evolution vis-a-vis growth and survival in the beer environment. Three shipwreck bacteria (one L. backii strain and two P. damnosus strains) and modern-day beer-spoilage isolates of the same two species were genome sequenced, characterized for hop iso-α-acid tolerance, and growth in degassed lager and wheat beer. In addition, plasmid variants of the modern-day P. damnosus strain were analyzed for the effect of plasmid-encoded genes on growth in lager beer. Coding content on two plasmids was identified as essential for LAB growth in modern lager beer. Three chromosomal regions containing genes related to sugar transport and cell wall polysaccharides were shared by pediococci able to grow in beer. Our results show that the three shipwreck bacteria lack the necessary plasmid-located genetic content to grow in modern lager beer, but carry additional genes related to acid tolerance and biofilm formation compared to their modern counterparts.}, } @article {pmid29126199, year = {2018}, author = {Choi, JY and Purugganan, MD}, title = {Evolutionary Epigenomics of Retrotransposon-Mediated Methylation Spreading in Rice.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {365-382}, pmid = {29126199}, issn = {1537-1719}, abstract = {Plant genomes contain numerous transposable elements (TEs), and many hypotheses on the evolutionary drivers that restrict TE activity have been postulated. Few models, however, have focused on the evolutionary epigenomic interaction between the plant host and its TE. The host genome recruits epigenetic factors, such as methylation, to silence TEs but methylation can spread beyond the TE sequence and influence the expression of nearby host genes. In this study, we investigated this epigenetic trade-off between TE and proximal host gene silencing by studying the epigenomic regulation of repressing long terminal repeat (LTR) retrotransposons (RTs) in Oryza sativa. Results showed significant evidence of methylation spreading originating from the LTR-RT sequences, and the extent of spreading was dependent on five factors: 1) LTR-RT family, 2) time since the LTR-RT insertion, 3) recombination rate of the LTR-RT region, 4) level of LTR-RT sequence methylation, and 5) chromosomal location. Methylation spreading had negative effects by reducing host gene expression, but only on host genes with LTR-RT inserted in its introns. Our results also suggested high levels of LTR-RT methylation might have a role in suppressing TE-mediated deleterious ectopic recombination. In the end, despite the methylation spreading, no strong epigenetic trade-off was detected and majority of LTR-RT may have only minor epigenetic effects on nearby host genes.}, } @article {pmid29126195, year = {2018}, author = {Buttner, MJ and Schäfer, M and Lawson, DM and Maxwell, A}, title = {Structural insights into simocyclinone as an antibiotic, effector ligand and substrate.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {1}, pages = {}, pmid = {29126195}, issn = {1574-6976}, support = {BBS/E/J/00000015//Biotechnology and Biological Sciences Research Council/United Kingdom ; BBS/E/J/00000201//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I002197/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/I002049/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; BB/J004561/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Anti-Bacterial Agents/*chemistry/metabolism/pharmacology ; DNA Gyrase/metabolism ; Enzyme Activation/drug effects ; Glycosides/*chemistry/pharmacology ; Ligands ; }, abstract = {Simocyclinones are antibiotics produced by Streptomyces and Kitasatospora species that inhibit the validated drug target DNA gyrase in a unique way, and they are thus of therapeutic interest. Structural approaches have revealed their mode of action, the inducible-efflux mechanism in the producing organism, and given insight into one step in their biosynthesis. The crystal structures of simocyclinones bound to their target (gyrase), the transcriptional repressor SimR and the biosynthetic enzyme SimC7 reveal fascinating insight into how molecular recognition is achieved with these three unrelated proteins.}, } @article {pmid29126122, year = {2018}, author = {Pacheco, MA and Matta, NE and Valkiunas, G and Parker, PG and Mello, B and Stanley, CE and Lentino, M and Garcia-Amado, MA and Cranfield, M and Kosakovsky Pond, SL and Escalante, AA}, title = {Mode and Rate of Evolution of Haemosporidian Mitochondrial Genomes: Timing the Radiation of Avian Parasites.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {383-403}, pmid = {29126122}, issn = {1537-1719}, support = {R01 GM080586/GM/NIGMS NIH HHS/United States ; R01 GM093939/GM/NIGMS NIH HHS/United States ; }, abstract = {Haemosporidians are a diverse group of vector-borne parasitic protozoa that includes the agents of human malaria; however, most of the described species are found in birds and reptiles. Although our understanding of these parasites' diversity has expanded by analyses of their mitochondrial genes, there is limited information on these genes' evolutionary rates. Here, 114 mitochondrial genomes (mtDNA) were studied from species belonging to four genera: Leucocytozoon, Haemoproteus, Hepatocystis, and Plasmodium. Contrary to previous assertions, the mtDNA is phylogenetically informative. The inferred phylogeny showed that, like the genus Plasmodium, the Leucocytozoon and Haemoproteus genera are not monophyletic groups. Although sensitive to the assumptions of the molecular dating method used, the estimated times indicate that the diversification of the avian haemosporidian subgenera/genera took place after the Cretaceous-Paleogene boundary following the radiation of modern birds. Furthermore, parasite clade differences in mtDNA substitution rates and strength of negative selection were detected. These differences may affect the biological interpretation of mtDNA gene lineages used as a proxy to species in ecological and parasitological investigations. Given that the mitochondria are critically important in the parasite life cycle stages that take place in the vector and that the transmission of parasites belonging to particular clades has been linked to specific insect families/subfamilies, this study suggests that differences in vectors have affected the mode of evolution of haemosporidian mtDNA genes. The observed patterns also suggest that the radiation of haemosporidian parasites may be the result of community-level evolutionary processes between their vertebrate and invertebrate hosts.}, } @article {pmid29125939, year = {2018}, author = {Rojas, ER and Huang, KC}, title = {Regulation of microbial growth by turgor pressure.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {62-70}, doi = {10.1016/j.mib.2017.10.015}, pmid = {29125939}, issn = {1879-0364}, support = {P50 GM107615/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*growth & development ; Bacterial Physiological Phenomena ; Cell Cycle ; Cell Wall/metabolism ; Cytoplasm/physiology ; Escherichia coli/metabolism ; Gram-Positive Bacteria/growth & development/physiology ; Osmotic Pressure ; *Pressure ; Schizosaccharomyces/cytology ; }, abstract = {Rapid changes in environmental osmolarity are a natural aspect of microbial lifestyles. The change in turgor pressure resulting from an osmotic shock alters the mechanical forces within the cell envelope, and can impact cell growth across a range of timescales, through a variety of mechanical mechanisms. Here, we first summarize measurements of turgor pressure in various organisms. We then review how the combination of microfluidic flow cells and quantitative image analysis has driven discovery of the diverse ways in which turgor pressure mechanically regulates bacterial growth, independent of the effect of cytoplasmic crowding. In Gram-positive, rod-shaped bacteria, reductions in turgor pressure cause decreased growth rate. Moreover, a hypoosmotic shock, which increases turgor pressure and membrane tension, leads to transient inhibition of cell-wall growth via electrical depolarization. By contrast, Gram-negative Escherichia coli is remarkably insensitive to changes in turgor. We discuss the extent to which turgor pressure impacts processes such as cell division that alter cell shape, in particular that turgor facilitates millisecond-scale daughter-cell separation in many Actinobacteria and eukaryotic fission yeast. This diverse set of responses showcases the potential for using osmotic shocks to interrogate how mechanical perturbations affect cellular processes.}, } @article {pmid29125938, year = {2018}, author = {Kavita, K and de Mets, F and Gottesman, S}, title = {New aspects of RNA-based regulation by Hfq and its partner sRNAs.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {53-61}, doi = {10.1016/j.mib.2017.10.014}, pmid = {29125938}, issn = {1879-0364}, mesh = {Escherichia coli/genetics/metabolism ; Escherichia coli Proteins/genetics/metabolism ; *Gene Expression Regulation, Bacterial ; Host Factor 1 Protein/*genetics/metabolism ; Protein Binding ; RNA Stability ; RNA, Bacterial/*genetics ; RNA, Messenger/genetics ; RNA, Small Untranslated/*genetics ; RNA-Binding Proteins/genetics/metabolism ; Repressor Proteins/genetics/metabolism ; }, abstract = {Hfq, an RNA chaperone, promotes the pairing of small RNAs (sRNAs) to target mRNAs, mediating post-transcriptional regulation of mRNA stability and translation. This regulation contributes to bacterial adaptation during stress and pathogenesis. Recent advances in sequencing techniques demonstrate the presence of sRNAs encoded not only in intergenic regions but also from the 3' and 5' UTRs of mRNAs, expanding sRNA regulatory networks. Additional layers of regulation by Hfq and its associated RNAs continue to be found. Newly identified RNA sponges modulate the activity of some sRNAs. A subset of sRNAs are proving to be bifunctional, able to pair with targets and also encoding small ORFs or binding other RNA binding proteins, such as CsrA. In addition, there are accumulating examples of Hfq inhibiting mRNA translation in the absence of sRNAs.}, } @article {pmid29125643, year = {2018}, author = {Ørsted, M and Rohde, PD and Hoffmann, AA and Sørensen, P and Kristensen, TN}, title = {Environmental variation partitioned into separate heritable components.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {136-152}, doi = {10.1111/evo.13391}, pmid = {29125643}, issn = {1558-5646}, abstract = {Trait variation is normally separated into genetic and environmental components, yet genetic factors also control the expression of environmental variation, encompassing plasticity across environmental gradients and within-environment responses. We defined four components of environmental variation: plasticity across environments, variability in plasticity, variation within environments, and differences in within-environment variation across environments. We assessed these components for cold tolerance across five rearing temperatures using the Drosophila melanogaster Genetic Reference Panel (DGRP). The four components were found to be heritable, and genetically correlated to different extents. By whole genome single marker regression, we detected multiple candidate genes controlling the four components and showed limited overlap in genes affecting them. Using the binary UAS-GAL4 system, we functionally validated the effects of a subset of candidate genes affecting each of the four components of environmental variation and also confirmed the genetic and phenotypic correlations obtained from the DGRP in distinct genetic backgrounds. We delineate selection targets associated with environmental variation and the constraints acting upon them, providing a framework for evolutionary and applied studies on environmental sensitivity. Based on our results we suggest that the traditional quantitative genetic view of environmental variation and genotype-by-environment interactions needs revisiting.}, } @article {pmid29125460, year = {2018}, author = {Ding, P and Bai, JL and Wang, TT and Sun, Y and Cao, CL and Jiang, JH and Qin, S}, title = {Nocardia rhizosphaerihabitans sp. nov., a novel actinomycete isolated from a coastal soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {192-197}, doi = {10.1099/ijsem.0.002481}, pmid = {29125460}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Lycium/*microbiology ; Nocardia/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An actinomycete strain, designated KLBMP S0039T, was isolated from the rhizosphere soil of Lycium Linn., collected from the coastal region in Lianyungang, Jiangsu Province, eastern PR China, and was studied to determine its taxonomic position. The isolate showed a combination of morphological and chemotaxonomic properties typical of the members of the genus Nocardia. The cell wall contained meso-diaminopimelic acid as the diagnostic diamino acid and the whole-cell sugars were galactose, arabinose, glucose and ribose. The predominant menaquinone was identified as MK-8(H4ω-cycl). The diagnostic phospholipids were found to be diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylinositol and unknown lipids. The predominant cellular fatty acids were identified as C16 : 0, C18 : 0, C18 : 1ω9c, and 10-methyl C18 : 0 [tuberculostearic acid (TBSA)]. The G+C content of the genomic DNA was determined to be 68.2 mol%. The 16S rRNA gene sequence similarity indicated that KLBMP S0039T was most closely related to Nocardia neocaledoniensis NBRC 108232T (99.4 % 16S rRNA gene sequence similarity) and Nocardia asteroides NBRC 15531T (99.2 %), similarities to other type strains of species of the genus Nocardia were found to be less than 98.6 %. However, DNA-DNA relatedness values and phenotypic data indicated that KLBMP S0039T could be clearly distinguished from the closely related species of the genus Nocardia. On the basis of polyphasic taxonomic data, it is concluded that KLBMP S0039T represents a novel species of the genus Nocardia, for which the name Nocardiarhizosphaerihabitans sp. nov. is proposed. The type strain is KLBMP S0039T (=KCTC 39693T=CGMCC 4.7329T).}, } @article {pmid29125459, year = {2018}, author = {Park, J and Kim, MK and Yun, BR and Han, JH and Kim, SB}, title = {Pseudogracilibacillus endophyticus sp. nov., a moderately thermophilic and halophilic species isolated from plant root.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {165-169}, doi = {10.1099/ijsem.0.002475}, pmid = {29125459}, issn = {1466-5034}, mesh = {Bacillaceae/classification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Oenothera biennis/*microbiology ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; Plant Roots/*microbiology ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive strain, designated DT7-02T, was isolated from the surface-sterilized root of Oenotherabiennis (evening primrose) and subjected to taxonomic characterization. Cells of DT7-02T were slender rod-shaped, motile by means of flagella, and oxidase- and catalase-positive. The colonies were circular, pinkish-yellow, opaque, glistering and 1-2 mm in diameter. The strain was moderately thermophilic and halophilic, as growth occurred at 20-44 °C (optimum 40 °C), pH 7-10 (optimum pH 8-9) and in the presence of 0-8 % of NaCl (optimum 4 %) in tryptic soy broth. The analysis of 16S rRNA gene sequences indicated that the strain represented a member of the genus Pseudogracilibacillus of the family Bacillaceae, and the sequence similarity was 96.5 % with Pseudogracilibacillus auburnensis P-207T and 95.9 % with Pseudogracilibacillus marinus NIOT-bflm-S4T. Other related taxa were Ornithinibacillus contaminans DSM 22953T and Sinibacillus soli KCTC 33117T, with 16S rRNA gene sequence similarities of 95.4 and 94.3 %, respectively. The major cellular fatty acids of DT7-02T were anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0. The DNA G+C content was 35.1 mol%, and the respiratory quinone was MK-7. The major polar lipids were phosphatidylglycerol, diphosphatidylglycerol and phosphatidylethanolamine. The combination of chemotaxonomic properties enabled differentiation of DT7-02T from the other two species of the genus Pseudogracilibacillus. The results of phylogenetic, phenotypic and chemotaxonomic analyses demonstrate that strain DT7-02T (=KCTC 33854T=JCM 31192T) merits recognition as representing a novel species of the genus Pseudogracilibacillus, for which the name Pseudogracilibacillusendophyticus sp. nov. is proposed.}, } @article {pmid29125458, year = {2018}, author = {Qu, Z and Bao, XD and Xie, QY and Zhao, YX and Yan, B and Dai, HF and Chen, HQ}, title = {Actinoplanes sediminis sp. nov., isolated from marine sediment.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {71-75}, doi = {10.1099/ijsem.0.002451}, pmid = {29125458}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; *Geologic Sediments ; Greece ; Micromonosporaceae/*classification/genetics/isolation & purification ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {An actinomycete strain M4I47T was isolated from sediment from Megas Gialos, Syros, Greece. The results of phylogenetic analysis of the 16S rRNA gene sequence of M4I47T indicated that the highest similarity was with Actinoplanes atraurantiacus Y16T (98.9 %), Actinoplanes deccanensis IFO 13994T (98.8 %), Actinoplanes digitatis IFO 12512T (98.1 %) and Actinoplanes abujensis A4029T (98.0 %). The cell wall of the novel isolate contained meso-diaminopimelic acid and the whole-cell sugars were xylose, arabinose and glucose. The predominant menaquinones were MK-9(H4), MK-9(H6) and MK-9(H2). The phospholipid profile comprised phosphatidylethanolamine, phosphatidylmethylethanolamine, phosphatidylinositol, phosphatidylinositol mannosides and an unknown phospholipid. The DNA G+C content was 71.5 mol%. Furthermore, a combination of DNA-DNA relatedness and some physiological and biochemical properties indicated that the novel strain could be readily distinguished from the most closely related species. On the basis of these phenotypic and genotypic data, M4I47T represents a novel species of the genus Actinoplanes, for which the name Actinoplanessediminis sp. nov. is proposed. The type strain is M4I47T (=CCTCC AA 2016022T=DSM 100965T).}, } @article {pmid29125457, year = {2018}, author = {Pillonetto, M and Arend, LN and Faoro, H and D'Espindula, HRS and Blom, J and Smits, THM and Mira, MT and Rezzonico, F}, title = {Emended description of the genus Phytobacter, its type species Phytobacter diazotrophicus (Zhang 2008) and description of Phytobacter ursingii sp. nov.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {176-184}, doi = {10.1099/ijsem.0.002477}, pmid = {29125457}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Brazil ; China ; DNA, Bacterial/genetics ; Gammaproteobacteria/*classification ; Genes, Bacterial ; Humans ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The species Phytobacter diazotrophicus and the associated genus Phytobacter were originally described by Zhanget al. [Arch Microbiol189 (2008), 431-439] on the basis of few endophytic nitrogen-fixing bacteria isolated from wild rice (Oryza rufipogon) in China. In this study, we demonstrate that a number of clinical isolates that were either described in the literature, preserved in culture collections, or obtained during a 2013 multi-state sepsis outbreak in Brazil also belong to the same genus. 16S rRNA gene sequencing, multilocus sequence analysis based on gyrB, rpoB, atpD and infB genes, as well as digital DNA-DNA hybridization support the existence of a second species within the genus Phytobacter. All isolates from the recent Brazilian outbreak, along with some older American clinical strains, were found to belong to the already described species Phytobacterdiazotrophicus, whereas three clinical strains retrieved in the USA over a time span of almost four decades, could be assigned to a new Phytobacter species. Implementation of an extended set of biochemical tests showed that the two Phytobacter species could phenotypically be discriminated from each other by the ability to utilize l-sorbose and d-serine. This feature was limited to the strains of the novel species described herein, for which the name Phytobacter ursingii sp. nov. is proposed, with ATCC 27989T (=CNCTC 5729T) as the designated type strain. An emended description of the species Phytobacter diazotrophicus and of the genus Phytobacter is also provided.}, } @article {pmid29125456, year = {2018}, author = {Yang, ZW and Salam, N and Mohany, M and Chinnathambi, A and Alharbi, SA and Xiao, M and Hozzein, WN and Li, WJ}, title = {Microbacterium album sp. nov. and Microbacterium deserti sp. nov., two halotolerant actinobacteria isolated from desert soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {217-222}, doi = {10.1099/ijsem.0.002485}, pmid = {29125456}, issn = {1466-5034}, mesh = {Actinobacteria/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; *Desert Climate ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Saudi Arabia ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/chemistry ; }, abstract = {Strains SYSU D8007T and SYSU D8014T were isolated from desert soil collected from Saudi Arabia. The two isolates were Gram-stain-positive, non-motile, aerobic and non-spore-forming. These strains were able to grow at 4-45 °C and in the presence of up to 8 % (w/v) NaCl. Strain SYSU D8007T could grow at pH 6.0-10.0, and strain SYSU D8014T at pH 5.0-10.0. They shared highest 16S rRNA gene sequence similarities with Microbacterium marinilacus YM11-607T and Microbacterium paludicola US15T. Menaquinones MK-11 and MK-12 were detected as the respiratory quinones. The polar lipid profiles of strains SYSU D8007T and SYSU D8014T consisted of diphosphatidylglycerol and phosphatidylglycerol, but differed in the number of unidentified glycolipids. Strain SYSU D8007T contained anteiso-C15 : 0, anteiso-C17 : 0 and iso-C16 : 0 as the predominant fatty acids, while strain SYSU D8014T contained anteiso-C15 : 0 and anteiso-C17 : 0 as the major fatty acids (>10 %). While glucose, rhamnose and ribose were detected in strain SYSU D8007T as the whole-cell sugars, galactose, glucose and rhamnose were present in strain SYSU D8014T. The genomic DNA G+C content of strains SYSU D8007T and SYSU D8014T was 72.2 and 73.6 mol%, respectively. Based on phenotypic, genotypic and phylogenetic characteristics, it can be concluded that strains SYSU D8007T and SYSU D8014T represent two novel species of the genus Microbacterium, for which the names Microbacterium album sp. nov. and Microbacterium deserti sp. nov. are proposed, respectively. The type strains are SYSU D8007T (=CGMCC 1.15794T=KCTC 39990T) and SYSU D8014T (=CPCC 204619T=KCTC39991T).}, } @article {pmid29125205, year = {2018}, author = {Molnar, JL and Diogo, R and Hutchinson, JR and Pierce, SE}, title = {Reconstructing pectoral appendicular muscle anatomy in fossil fish and tetrapods over the fins-to-limbs transition.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1077-1107}, doi = {10.1111/brv.12386}, pmid = {29125205}, issn = {1469-185X}, abstract = {The question of how tetrapod limbs evolved from fins is one of the great puzzles of evolutionary biology. While palaeontologists, developmental biologists, and geneticists have made great strides in explaining the origin and early evolution of limb skeletal structures, that of the muscles remains largely unknown. The main reason is the lack of consensus about appendicular muscle homology between the closest living relatives of early tetrapods: lobe-finned fish and crown tetrapods. In the light of a recent study of these homologies, we re-examined osteological correlates of muscle attachment in the pectoral girdle, humerus, radius, and ulna of early tetrapods and their close relatives. Twenty-nine extinct and six extant sarcopterygians were included in a meta-analysis using information from the literature and from original specimens, when possible. We analysed these osteological correlates using parsimony-based character optimization in order to reconstruct muscle anatomy in ancestral lobe-finned fish, tetrapodomorph fish, stem tetrapods, and crown tetrapods. Our synthesis revealed that many tetrapod shoulder muscles probably were already present in tetrapodomorph fish, while most of the more-distal appendicular muscles either arose later from largely undifferentiated dorsal and ventral muscle masses or did not leave clear correlates of attachment in these taxa. Based on this review and meta-analysis, we postulate a stepwise sequence of specific appendicular muscle acquisitions, splits, and fusions that led from the ancestral sarcopterygian pectoral fin to the ancestral tetrapod forelimb. This sequence largely agrees with previous hypotheses based on palaeontological and comparative work, but it is much more comprehensive in terms of both muscles and taxa. Combined with existing information about the skeletal system, our new synthesis helps to illuminate the genetic, developmental, morphological, functional, and ecological changes that were key components of the fins-to-limbs transition.}, } @article {pmid29124898, year = {2018}, author = {Hölscher, T and Schiklang, T and Dragoš, A and Dietel, AK and Kost, C and Kovács, ÁT}, title = {Impaired competence in flagellar mutants of Bacillus subtilis is connected to the regulatory network governed by DegU.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {23-32}, doi = {10.1111/1758-2229.12601}, pmid = {29124898}, issn = {1758-2229}, abstract = {The competent state is a developmentally distinct phase, in which bacteria are able to take up and integrate exogenous DNA into their genome. Bacillus subtilis is one of the naturally competent bacterial species and the domesticated laboratory strain 168 is easily transformable. In this study, we report a reduced transformation frequency of B. subtilis mutants lacking functional and structural flagellar components. This includes hag, the gene encoding the flagellin protein forming the filament of the flagellum. We confirm that the observed decrease of the transformation frequency is due to reduced expression of competence genes, particularly of the main competence regulator gene comK. The impaired competence is due to an increase in the phosphorylated form of the response regulator DegU, which is involved in regulation of both flagellar motility and competence. Altogether, our study identified a close link between motility and natural competence in B. subtilis suggesting that hindrance in motility has great impact on differentiation of this bacterium not restricted only to the transition towards sessile growth stage.}, } @article {pmid29124895, year = {2018}, author = {Lawson, CA and Raina, JB and Kahlke, T and Seymour, JR and Suggett, DJ}, title = {Defining the core microbiome of the symbiotic dinoflagellate, Symbiodinium.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {7-11}, doi = {10.1111/1758-2229.12599}, pmid = {29124895}, issn = {1758-2229}, abstract = {Dinoflagellates of the genus Symbiodinium underpin the survival and ecological success of corals. The use of cultured strains has been particularly important to disentangle the complex life history of Symbiodinium and their contribution to coral host physiology. However, these cultures typically harbour abundant bacterial communities which likely play important, but currently unknown, roles in Symbiodinium biology. We characterized the bacterial communities living in association with a wide phylogenetic diversity of Symbiodinium cultures (18 types spanning 5 clades) to define the core Symbiodinium microbiome. Similar to other systems, bacteria were nearly two orders of magnitude more numerically abundant than Symbiodinium cells and we identified three operational taxonomic units (OTUs) which were present in all cultures. These represented the α-proteobacterium Labrenzia and the γ-proteobacteria Marinobacter and Chromatiaceae. Based on the abundance and functional potential of bacteria harboured in these cultures, their contribution to Symbiodinium physiology can no longer be ignored.}, } @article {pmid29124888, year = {2018}, author = {Liu, Y and Palmer, SR and Chang, H and Combs, AN and Burne, RA and Koo, H}, title = {Differential oxidative stress tolerance of Streptococcus mutans isolates affects competition in an ecological mixed-species biofilm model.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {12-22}, pmid = {29124888}, issn = {1758-2229}, support = {T90 DE021990/DE/NIDCR NIH HHS/United States ; R01 DE013239/DE/NIDCR NIH HHS/United States ; R01 DE025220/DE/NIDCR NIH HHS/United States ; R01 DE018023/DE/NIDCR NIH HHS/United States ; R01 DE025832/DE/NIDCR NIH HHS/United States ; K99 DE023833/DE/NIDCR NIH HHS/United States ; R00 DE023833/DE/NIDCR NIH HHS/United States ; }, abstract = {Streptococcus mutans strongly influences the development of pathogenic biofilms associated with dental caries. Our understanding of S. mutans behaviour in biofilms is based on a few well-characterized laboratory strains; however, individual isolates vary widely in genome content and virulence-associated phenotypes, such as biofilm formation and environmental stress sensitivity. Using an ecological biofilm model, we assessed the impact of co-cultivation of several S. mutans isolates with Streptococcus oralis and Actinomyces naeslundii on biofilm composition following exposure to sucrose. The laboratory reference strain S. mutans UA159 and clinical isolates Smu44 (most aciduric), Smu56 (altered biofilm formation) and Smu81 (more sensitive to oxidative stress) were used. Our data revealed S. mutans isolates varied in their ability to compete and become dominant in the biofilm after the addition of sucrose, and this difference correlated with sensitivity to H2 O2 produced by S. oralis. Smu81 was particularly sensitive to H2 O2 and could not compete with S. oralis in mixed-species biofilm, despite forming robust biofilms on its own. Thus, diminished oxidative stress tolerance in S. mutans isolates can impair their ability to compete in complex biofilms, even in the presence of sucrose, which could influence the progression of a healthy biofilm community to one capable of causing disease.}, } @article {pmid29124879, year = {2018}, author = {Martinson, GO and Pommerenke, B and Brandt, FB and Homeier, J and Burneo, JI and Conrad, R}, title = {Hydrogenotrophic methanogenesis is the dominant methanogenic pathway in neotropical tank bromeliad wetlands.}, journal = {Environmental microbiology reports}, volume = {10}, number = {1}, pages = {33-39}, doi = {10.1111/1758-2229.12602}, pmid = {29124879}, issn = {1758-2229}, abstract = {Several thousands of tank bromeliads per hectare of neotropical forest create a unique wetland ecosystem that emits substantial amounts of CH4 . Tank bromeliads growing in the forest canopy (functional type-II tank bromeliads) were found to emit more CH4 than tank bromeliads growing on the forest floor (functional type-I tank bromeliads) but the reasons for this difference and the underlying microbial CH4 -cycling processes have not been studied. Therefore, we characterized archaeal communities in bromeliad tanks of the two different functional types in a neotropical montane forest of southern Ecuador using terminal-restriction fragment length polymorphism (T-RFLP) and performed tank-slurry incubations to measure CH4 production potential, stable carbon isotope fractionation and pathway of CH4 formation. The archaeal community composition was dominated by methanogens and differed between bromeliad functional types. Hydrogenotrophic Methanomicrobiales were the dominant methanogens and hydrogenotrophic methanogenesis was the dominant methanogenic pathway among all bromeliads. The relative abundance of aceticlastic Methanosaetaceae and the relative contribution of aceticlastic methanogenesis increased in type-I tank bromeliads probably due to more oxic conditions in type-I than in type-II bromeliads leading to the previously observed lower in situ CH4 emissions from type-I tank bromeliads but to higher CH4 production potentials in type-I tank bromeliad slurries.}, } @article {pmid29124873, year = {2018}, author = {Fernandes, VMC and Machado de Lima, NM and Roush, D and Rudgers, J and Collins, SL and Garcia-Pichel, F}, title = {Exposure to predicted precipitation patterns decreases population size and alters community structure of cyanobacteria in biological soil crusts from the Chihuahuan Desert.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {259-269}, doi = {10.1111/1462-2920.13983}, pmid = {29124873}, issn = {1462-2920}, abstract = {Cyanobacteria typically colonize the surface of arid soils, building biological soil crust (biocrusts) that provide a variety of ecosystem benefits, ranging from fertilization to stabilization against erosion. We investigated how future scenarios in precipitation anticipated for the Northern Chihuahuan Desert affected abundance and composition of biocrust cyanobacteria in two grassland ecosystems. Scenarios included a decrease in precipitation and a delay of monsoon rainfall. After three years, both treatments negatively affected cyanobacteria, although the effects of monsoon delay were milder than those of decreased precipitation. Mature biocrusts in black grama grassland suffered severe losses in cyanobacterial biomass and diversity, but compositionally simpler biocrusts in blue grama-dominated grassland maintained biomass, only suffering diversity losses. This could be partially explained by the differential sensitivity of cyanobacterial taxa: nitrogen-fixing Scytonema spp. were the most sensitive, followed by phylotypes in the Microcoleus steenstrupii complex. Microcoleus vaginatus was the least affected in all cases, but is known to be very sensitive to warming. We predict that altered precipitation will tend to prevent biocrusts from reaching successional maturity, selecting for M. vaginatus over competing M. steenstrupii, among pioneer biocrust-formers. A shift towards heat-sensitive M. vaginatus could ultimately destabilize biocrusts when precipitation changes are combined with global warming.}, } @article {pmid29124868, year = {2018}, author = {Fadhlaoui, K and Ben Hania, W and Armougom, F and Bartoli, M and Fardeau, ML and Erauso, G and Brasseur, G and Aubert, C and Hamdi, M and Brochier-Armanet, C and Dolla, A and Ollivier, B}, title = {Obligate sugar oxidation in Mesotoga spp., phylum Thermotogae, in the presence of either elemental sulfur or hydrogenotrophic sulfate-reducers as electron acceptor.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {281-292}, doi = {10.1111/1462-2920.13995}, pmid = {29124868}, issn = {1462-2920}, abstract = {Mesotoga prima strain PhosAc3 is a mesophilic representative of the phylum Thermotogae comprising only fermentative bacteria so far. We show that while unable to ferment glucose, this bacterium is able to couple its oxidation to reduction of elemental sulfur. We demonstrate furthermore that M. prima strain PhosAc3 as well as M. prima strain MesG1 and Mesotoga infera are able to grow in syntrophic association with sulfate-reducing bacteria (SRB) acting as hydrogen scavengers through interspecies hydrogen transfer. Hydrogen production was higher in M. prima strain PhosAc3 cells co-cultured with SRB than in cells cultured alone in the presence of elemental sulfur. We propose that the efficient sugar-oxidizing metabolism by M. prima strain PhosAc3 in syntrophic association with a hydrogenotrophic sulfate-reducing bacterium can be extrapolated to all members of the Mesotoga genus. Genome comparison of Thermotogae members suggests that the metabolic difference between Mesotoga and Thermotoga species (sugar oxidation versus fermentation) is mainly due to the absence of the bifurcating [FeFe]-hydrogenase in the former. Such an obligate oxidative process for using sugars, unusual within prokaryotes, is the first reported within the Thermotogae. It is hypothesized to be of primary ecological importance for growth of Mesotoga spp. in the environments that they inhabit.}, } @article {pmid29124862, year = {2018}, author = {Albers, P and Lood, C and Özturk, B and Horemans, B and Lavigne, R and van Noort, V and De Mot, R and Marchal, K and Sanchez-Rodriguez, A and Springael, D}, title = {Catabolic task division between two near-isogenic subpopulations co-existing in a herbicide-degrading bacterial consortium: consequences for the interspecies consortium metabolic model.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {85-96}, doi = {10.1111/1462-2920.13994}, pmid = {29124862}, issn = {1462-2920}, abstract = {Variovorax sp. WDL1 mediates hydrolysis of the herbicide linuron into 3,4-dichloroaniline (DCA) and N,O-dimethylhydroxylamine in a tripartite bacterial consortium with Comamonas testosteroni WDL7 and Hyphomicrobium sulfonivorans WDL6. Although strain WDL1 contains the dcaQTA1A2B operon for DCA oxidation, this conversion is mainly performed by WDL7. Phenotypic diversification observed in WDL1 cultures and scrutiny of the WDL1 genome suggest that WDL1 cultures consist of two dedicated subpopulations, i.e., a linuron-hydrolysing subpopulation (Lin + DCA-) and a DCA-oxidizing subpopulation (Lin-DCA+). Whole genome analysis of strains representing the respective subpopulations revealed that they are identical, aside from the presence of hylA (in Lin + DCA- cells) and the dcaQTA1A2B gene cluster (in Lin-DCA+ cells), and that these catabolic gene modules replace each other at exactly the same locus on a 1380 kb extra-chromosomal element that shows plasmid gene functions including genes for transferability by conjugation. Both subpopulations proliferate in consortium biofilms fed with linuron, but Lin + DCA- cells compose the main WDL1 subpopulation. Our observations instigated revisiting the interactions within the consortium and suggest that the physical separation of two essential linuron catabolic gene clusters in WDL1 by mutually exclusive integration in the same mobile genetic element is key to the existence of WDL1 in a consortium mode.}, } @article {pmid29124861, year = {2018}, author = {Certner, RH and Vollmer, SV}, title = {Inhibiting bacterial quorum sensing arrests coral disease development and disease-associated microbes.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {645-657}, doi = {10.1111/1462-2920.13991}, pmid = {29124861}, issn = {1462-2920}, abstract = {Among the greatest threats to coral reefs are coral epizootics, which are increasing in frequency and severity across many reef ecosystems. In particular, white band disease (WBD) has devastated Caribbean acroporid populations since its initial outbreak in 1979. However, despite its widespread and damaging effects, the aetiology of WBD remains largely unresolved. Here, we examine the role of quorum sensing within bacterial communities associated with WBD-infected Acropora cervicornis. Microbial communities isolated from WBD-infected corals were exposed to quorum sensing inhibitor (QSI) - a N-acyl homoserine lactone autoinducer antagonist - and then dosed onto healthy test corals. WBD-associated bacteria supplemented with QSI lost the ability to establish disease, while healthy corals exposed to uninhibited WBD bacterial communities became infected within two days. Microbial 16S rRNA metagenomic sequencing analyses were then used to identify shifts in bacterial communities due to QSI exposure on WBD-associated bacterial communities. Our results demonstrated that Vibrionaceae and Flavobacteriaceae abundances were strongly inhibited by the addition of QSI to WBD-infected corals, whereas putative coral symbiont Endozoicomonas and Halomonadaceae abundances decrease dramatically in diseased corals.}, } @article {pmid29124859, year = {2018}, author = {Lemay, MA and Martone, PT and Keeling, PJ and Burt, JM and Krumhansl, KA and Sanders, RD and Wegener Parfrey, L}, title = {Sympatric kelp species share a large portion of their surface bacterial communities.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {658-670}, doi = {10.1111/1462-2920.13993}, pmid = {29124859}, issn = {1462-2920}, abstract = {Kelp forest ecosystems are biodiversity hotspots, providing habitat for dense assemblages of marine organisms and nutrients for marine and terrestrial food webs. The surfaces of kelps support diverse microbial communities that facilitate the transfer of carbon from algal primary production to higher trophic levels. We quantified the diversity of bacteria on the surfaces of eight sympatric kelp species from four sites in British Columbia. Kelp-associated bacterial communities are significantly different from their environment, even though 86% of their bacterial taxa are shared with seawater and 97% are shared with rocky substrate. This differentiation is driven by differences in relative abundance of the bacterial taxa present. Similarly, a large portion of bacterial taxa (37%) is shared among all eight kelp species, yet differential abundance of bacterial taxa underlies differences in community structure among species. Kelp-associated bacterial diversity does not track host phylogeny; instead bacterial community composition is correlated with the life-history strategy of the host, with annual and perennial kelps supporting divergent bacterial communities. These data provide the first community-scale investigation of kelp forest-associated bacterial diversity. More broadly, this study provides insight into mechanisms that may structure bacterial communities among closely related sympatric host species.}, } @article {pmid29124858, year = {2018}, author = {Guerrero-Feijóo, E and Sintes, E and Herndl, GJ and Varela, MM}, title = {High dark inorganic carbon fixation rates by specific microbial groups in the Atlantic off the Galician coast (NW Iberian margin).}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {602-611}, doi = {10.1111/1462-2920.13984}, pmid = {29124858}, issn = {1462-2920}, abstract = {Bulk dark dissolved inorganic carbon (DIC) fixation rates were determined and compared to microbial heterotrophic production in subsurface, meso- and bathypelagic Atlantic waters off the Galician coast (NW Iberian margin). DIC fixation rates were slightly higher than heterotrophic production throughout the water column, however, more prominently in the bathypelagic waters. Microautoradiography combined with catalyzed reporter deposition fluorescence in situ hybridization (MICRO-CARD-FISH) allowed us to identify several microbial groups involved in dark DIC uptake. The contribution of SAR406 (Marinimicrobia), SAR324 (Deltaproteobacteria) and Alteromonas (Gammaproteobacteria) to the dark DIC fixation was significantly higher than that of SAR202 (Chloroflexi) and Thaumarchaeota, in agreement with their contribution to microbial abundance. Q-PCR on the gene encoding for the ammonia monooxygenase subunit A (amoA) from the putatively high versus low ammonia concentration ecotypes revealed their depth-stratified distribution pattern. Taken together, our results indicate that chemoautotrophy is widespread among microbes in the dark ocean, particularly in bathypelagic waters. This chemolithoautotrophic biomass production in the dark ocean, depleted in bio-available organic matter, might play a substantial role in sustaining the dark ocean's food web.}, } @article {pmid29124854, year = {2018}, author = {Pittera, J and Jouhet, J and Breton, S and Garczarek, L and Partensky, F and Maréchal, É and Nguyen, NA and Doré, H and Ratin, M and Pitt, FD and Scanlan, DJ and Six, C}, title = {Thermoacclimation and genome adaptation of the membrane lipidome in marine Synechococcus.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {612-631}, doi = {10.1111/1462-2920.13985}, pmid = {29124854}, issn = {1462-2920}, abstract = {The marine cyanobacteria of the genus Synechococcus are important primary producers, displaying a wide latitudinal distribution that is underpinned by diversification into temperature ecotypes. The physiological basis underlying these ecotypes is poorly known. In many organisms, regulation of membrane fluidity is crucial for acclimating to variations in temperature. Here, we reveal the detailed composition of the membrane lipidome of the model strain Synechococcus sp. WH7803 and its response to temperature variation. Unlike freshwater strains, membranes are almost devoid of C18, mainly containing C14 and C16 chains with no more than two unsaturations. In response to cold, we observed a rarely observed process of acyl chain shortening that likely induces membrane thinning, along with specific desaturation activities. Both of these mechanisms likely regulate membrane fluidity, facilitating the maintenance of efficient photosynthetic activity. A comprehensive examination of 53 Synechococcus genomes revealed clade-specific gene sets regulating membrane lipids. In particular, the genes encoding desaturase enzymes, which is a key to the temperature stress response, appeared to be temperature ecotype-specific, with some of them originating from lateral transfers. Our study suggests that regulation of membrane fluidity has been among the important adaptation processes for the colonization of different thermal niches by marine Synechococcus.}, } @article {pmid29124852, year = {2018}, author = {Steele, DJ and Kimmance, SA and Franklin, DJ and Airs, RL}, title = {Occurrence of chlorophyll allomers during virus-induced mortality and population decline in the ubiquitous picoeukaryote Ostreococcus tauri.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {588-601}, doi = {10.1111/1462-2920.13980}, pmid = {29124852}, issn = {1462-2920}, abstract = {During viral infection and growth limitation of the picoeukaryote Ostreococcus tauri, we examined the relationship between membrane permeability, oxidative stress and chlorophyll allomers (oxidation products). Chlorophyll allomers were measured in batch-cultures of O. tauri in parallel with maximum quantum efficiency of photosystem II photochemistry (Fv /Fm), carotenoids, and reactive oxygen species and membrane permeability using fluorescent probes (CM-H2 DCFDA and SYTOX-Green). Viral infection led to mass cell lysis of the O. tauri cells within 48 h. The concentration of the allomer hydroxychlorophyll a peaked with a 16-fold increase (relative to chlorophyll-a) just after the major lysis event. In contrast, cell death due to growth limitation resulted in a twofold increase in allomer production, relative to chl-a. Two allomers were detected solely in association with O. tauri debris after viral lysis, and unlike other allomers were not observed before viral lysis, or during cell death due to growth limitation. Conversely, the component chl-aP276 was found in the highest concentrations relative to chl-a, in exponentially growing O. tauri. The components described have potential as indicators of mode of phytoplankton mortality, and of population growth.}, } @article {pmid29124849, year = {2018}, author = {Li, DX and Zhang, H and Chen, XH and Xie, ZX and Zhang, Y and Zhang, SF and Lin, L and Chen, F and Wang, DZ}, title = {Metaproteomics reveals major microbial players and their metabolic activities during the blooming period of a marine dinoflagellate Prorocentrum donghaiense.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {632-644}, doi = {10.1111/1462-2920.13986}, pmid = {29124849}, issn = {1462-2920}, abstract = {Interactions between bacteria and phytoplankton during bloom events are essential for both partners, which impacts their physiology, alters ambient chemistry and shapes ecosystem diversity. Here, we investigated the community structure and metabolic activities of free-living bacterioplankton in different blooming phases of a dinoflagellate Prorocentrum donghaiense using a metaproteomic approach. The Fibrobacteres-Chlorobi-Bacteroidetes group, Rhodobacteraceae, SAR11 and SAR86 clades contributed largely to the bacterial community in the middle-blooming phase while the Pseudoalteromonadaceae exclusively dominated in the late-blooming phase. Transporters and membrane proteins, especially TonB-dependent receptors were highly abundant in both blooming phases. Proteins involved in carbon metabolism, energy metabolism and stress response were frequently detected in the middle-blooming phase while proteins participating in proteolysis and central carbon metabolism were abundant in the late-blooming phase. Beta-glucosidase with putative algicidal capability was identified from the Pseudoalteromonadaceae only in the late-blooming phase, suggesting an active role of this group in lysing P. donghaiense cells. Our results indicated that diverse substrate utilization strategies and different capabilities for environmental adaptation among bacteria shaped their distinct niches in different bloom phases, and certain bacterial species from the Pseudoalteromonadaceae might be crucial for the termination of a dinoflagellate bloom.}, } @article {pmid29124848, year = {2018}, author = {Roggo, C and Picioreanu, C and Richard, X and Mazza, C and van Lintel, H and van der Meer, JR}, title = {Quantitative chemical biosensing by bacterial chemotaxis in microfluidic chips.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {241-258}, doi = {10.1111/1462-2920.13982}, pmid = {29124848}, issn = {1462-2920}, abstract = {Whole-cell bacterial bioreporters are proposed as alternatives to chemical analysis of, for example, pollutants in environmental compartments. Commonly based on reporter gene induction, bioreporters produce a detectable signal within 30 min to a few hours after exposure to the chemical target, which is impractical for applications aiming at a fast response. In an attempt to attain faster readout but maintain flexibility of chemical targeting, we explored the concept for quantitative chemical sensing by bacterial chemotaxis. Chemotaxis was quantified from enrichment of cells across a 600 µm-wide chemical gradient stabilized by parallel flow in a microfluidic chip, further supported by transport and chemotaxis steady state and kinetic modelling. As proof-of-concept, we quantified Escherichia coli chemotaxis towards serine, aspartate and methylaspartate as a function of attractant concentration and exposure time. E. coli chemotaxis enrichment increased sharply between 0 and 10 µM serine, before saturating at 100 µM. The chemotaxis accumulation rate was maximal at 10 µM serine, leading to observable cell enrichment within 5 min. The potential application for biosensing of environmental toxicants was investigated by quantifying chemotaxis of Cupriavidus pinatubonensis JMP134 towards the herbicide 2,4-dichlorophenoxyacetate. Our results show that bacterial chemotaxis can be quantified on a scale of minutes and may be used for developing faster bioreporter assays.}, } @article {pmid29124846, year = {2018}, author = {Wang, HC and Huang, JC and Lin, YH and Chen, YH and Hsieh, MI and Choi, PC and Lo, HJ and Liu, WL and Hsu, CS and Shih, HI and Wu, CJ and Chen, YC}, title = {Prevalence, mechanisms and genetic relatedness of the human pathogenic fungus Aspergillus fumigatus exhibiting resistance to medical azoles in the environment of Taiwan.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {270-280}, doi = {10.1111/1462-2920.13988}, pmid = {29124846}, issn = {1462-2920}, abstract = {Emerging azole resistance in Aspergillus fumigatus poses a serious threat to human health. This nationwide surveillance study investigated the prevalence and molecular characteristics of azole-resistant A. fumigatus environmental isolates in Taiwan, an island country with increasing use of azole fungicides. Of the 2760 air and soil samples screened from 2014 to 2016, 451 A. fumigatus isolates were recovered from 266 samples and 34 isolates from 29 samples displayed resistance to medical azoles (itraconazole, voriconazole or posaconazole). The resistance prevalence was 10.9% and 7.5% in A. fumigatus-positive samples and isolates respectively. Most (29, 85.3%) azole-resistant isolates harboured TR34 /L98H mutations, which were widely distributed, clustered genetically with clinical isolates, and had growth rates that were similar to those of the wild-type isolates. Microsatellite genotyping revealed both the global spread of the TR34 /L98H isolates and the occurrence of TR34 /L98H/S297T/F495I isolates belonging to local microsatellite genotypes. AfuMDR3 and atrF, two efflux transporter genes, were constitutively upregulated in two individual resistant isolates without cyp51A mutations, highlighting their potential roles in azole resistance. These results emphasize the need for periodic environmental surveillance at the molecular level in regions in which azole fungicides are applied, and agricultural fungicide management strategies that generate less selective pressure should be investigated.}, } @article {pmid29122672, year = {2018}, author = {Zhang, ST and Song, XN and Li, N and Zhang, K and Liu, GS and Li, XD and Wang, ZZ and He, XB and Wang, GF and Shao, HF}, title = {Influence of high-carbon basal fertiliser on the structure and composition of a soil microbial community under tobacco cultivation.}, journal = {Research in microbiology}, volume = {169}, number = {2}, pages = {115-126}, doi = {10.1016/j.resmic.2017.10.004}, pmid = {29122672}, issn = {1769-7123}, mesh = {Bacteria/classification/genetics/*isolation & purification/metabolism ; Biodiversity ; Carbon/*analysis/metabolism ; Fertilizers/*analysis ; Fungi/classification/genetics/*isolation & purification/metabolism ; Phosphorus/analysis/metabolism ; Soil/chemistry ; *Soil Microbiology ; Tobacco/*growth & development/microbiology ; }, abstract = {Soil microorganisms play a crucial role in cycling soil nutrients and providing organic nutrients for plant growth and development. Fertilisation balances soil fertility and quality, and affects soil microbial communities. Fertilisation is a frontier subject in agricultural and environmental sciences. Here we showed that the application of high-carbon basal fertiliser treatment could improve the tobacco yield and quality when compared to chemical fertiliser, high-carbon basal fertiliser and mixed high-carbon chemical fertiliser. The potential reason is that different fertiliser treatments influence soil fertility, such as nitrogen, phosphorus, and other contents, besides soil organic matter. Further experiments revealed that populations of bacteria, fungi and actinomycetes fluctuated during tobacco development under different fertilisation treatments. Then we performed high-throughput sequencing of the 16S rRNA gene, and the results showed that the fertilisation treatments had significant effects on the microbial community, particularly within the finer taxonomic divisions or non-dominant taxa. Moreover, proteobacteria and fungal genera had significantly different relative abundances during tobacco growth under various tobacco developmental stages and fertilisation treatments. These results indicated that mixed high-carbon chemical fertiliser could improve soil fertility by influencing the soil microorganism, and that the fertilisation treatments impacted on the structure and composition of the microbial community, and especially the diversity of non-dominant taxa. However, more studies are needed to confirm their reliability.}, } @article {pmid29122650, year = {2018}, author = {Dorchin, A and López-Uribe, MM and Praz, CJ and Griswold, T and Danforth, BN}, title = {Phylogeny, new generic-level classification, and historical biogeography of the Eucera complex (Hymenoptera: Apidae).}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {81-92}, doi = {10.1016/j.ympev.2017.10.007}, pmid = {29122650}, issn = {1095-9513}, mesh = {Animals ; Bees/anatomy & histology/*classification ; Databases, Genetic ; Likelihood Functions ; *Phylogeny ; *Phylogeography ; Quantitative Trait, Heritable ; Sequence Analysis, DNA ; }, abstract = {The longhorn bee tribe Eucerini (Hymenoptera: Apidae) is a diverse, widely distributed group of solitary bees that includes important pollinators of both wild and agricultural plants. About half of the species in the tribe are currently assigned to the genus Eucera and to a few other related genera. In this large genus complex, comprising ca. 390 species, the boundaries between genera remain ambiguous due to morphological intergradation among taxa. Using ca. 6700 aligned nucleotide sites from six gene fragments, 120 morphological characters, and more than 100 taxa, we present the first comprehensive molecular, morphological, and combined phylogenetic analyses of the 'Eucera complex'. The revised generic classification that we propose is congruent with our phylogeny and maximizes both generic stability and ease of identification. Under this new classification most generic names are synonymized under an expanded genus Eucera. Thus, Tetralonia, Peponapis, Xenoglossa, Cemolobus, and Syntrichalonia are reduced to subgeneric rank within Eucera, and Synhalonia is retained as a subgenus of Eucera. Xenoglossodes is reestablished as a valid subgenus of Eucera while Tetraloniella is synonymized with Tetralonia and Cubitalia with Eucera. In contrast, we suggest that the venusta-group of species, currently placed in the subgenus Synhalonia, should be recognized as a new genus. Our results demonstrate the need to evaluate convergent loss or gain of important diagnostic traits to minimize the use of potentially homoplasious characters when establishing classifications. Lastly, we show that the Eucera complex originated in the Nearctic region in the late Oligocene, and dispersed twice into the Old World. The first dispersal event likely occurred 24.2-16.6 mya at a base of a clade of summer-active bees restricted to warm region of the Old World, and the second 13.9-12.3 mya at the base of a clade of spring-active bees found in cooler regions of the Holarctic. Our results further highlight the role of Beringia as a climate-regulated corridor for bees.}, } @article {pmid29122517, year = {2018}, author = {Galán-Puchades, MT}, title = {The Guinea Worm: A Zoonotic Parasite of Dogs.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {3-4}, doi = {10.1016/j.pt.2017.10.003}, pmid = {29122517}, issn = {1471-5007}, mesh = {Africa/epidemiology ; Animals ; Dogs ; Dracunculiasis/epidemiology/*prevention & control/*transmission ; *Dracunculus Nematode ; Humans ; Zoonoses/epidemiology/prevention & control/transmission ; }, } @article {pmid29122447, year = {2018}, author = {Sariol, CA and Nogueira, ML and Vasilakis, N}, title = {A Tale of Two Viruses: Does Heterologous Flavivirus Immunity Enhance Zika Disease?.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {186-190}, doi = {10.1016/j.tim.2017.10.004}, pmid = {29122447}, issn = {1878-4380}, support = {U01 AI115577/AI/NIAID NIH HHS/United States ; R24 AI120942/AI/NIAID NIH HHS/United States ; P40 OD012217/OD/NIH HHS/United States ; U42 OD021458/OD/NIH HHS/United States ; }, mesh = {Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; *Antibody-Dependent Enhancement ; Dengue/virology ; Dengue Virus/immunology/pathogenicity ; Flaviviridae Infections/*immunology ; Flavivirus/*immunology ; Humans ; Primate Diseases/immunology ; Zika Virus/*immunology/pathogenicity ; Zika Virus Infection/*immunology ; }, abstract = {The rise of Zika virus (ZIKV) and its unusual clinical manifestations provided ground for speculative debate. The clinical severity of secondary dengue virus (DENV) infections is associated with antibody-dependent enhancement (ADE), and it was recently suggested that previous exposure to DENV may worsen ZIKV clinical outcomes. In this Opinion article we analyze the relationship among different flaviviruses and ADE. We discuss new evidence obtained in non-human primates and human cohorts demonstrating that there is no correlation to ADE when ZIKV infection occurs in the presence of pre-existing DENV immunity. We propose a redefinition of ADE in the context of complex immunological flavivirus interactions to provide a more objective perspective when translating in vitro or in vivo observations into the clinical setting.}, } @article {pmid29122382, year = {2018}, author = {Colegrave, N and Ruxton, GD}, title = {Using Biological Insight and Pragmatism When Thinking about Pseudoreplication.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {1}, pages = {28-35}, doi = {10.1016/j.tree.2017.10.007}, pmid = {29122382}, issn = {1872-8383}, mesh = {Biological Evolution ; Ecology/*methods ; Periodicals as Topic ; *Research Design ; }, abstract = {Pseudoreplication is controversial across experimental biology. Researchers in the same field can disagree on whether a given study suffers from pseudoreplication and on to what extent any pseudoreplication undermines the value of a study. A recent survey indicated that concerns about pseudoreplication can strongly impact peer review of manuscripts submitted for publication. Here we explore controversies around pseudoreplication, identify issues requiring resolution, and in each case offer a resolution. We emphasise that having non-independence in data points and pseudoreplicating are not the same thing. Researchers should be able to demonstrate that in a given experiment they have minimised and controlled the risk of non-independence weakening their study. If they do that to the satisfaction of others, they have avoided pseudoreplication.}, } @article {pmid29120033, year = {2018}, author = {Amado, A and Batista, C and Campos, PRA}, title = {A theoretical approach to the size-complexity rule.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {18-29}, doi = {10.1111/evo.13392}, pmid = {29120033}, issn = {1558-5646}, abstract = {The so-called size-complexity rule claims the existence of a positive correlation between organism size and number of cell types. In this spirit, here we address the relationship between organism size and number of potential tasks that can be performed. The modeling relies on the assumption that the states of the cells within the aggregates are such that the maximum fitness is realized, but also relies on the existence of tradeoffs among the distinct functions. For group sizes larger than the number of potential tasks, fitness maximization is attained when all cells in group specialize in a given task. Under this scenario, the number of potential tasks equals the number of cell types. We have found that the morphology and the topology of aggregates, as well as the developmental mode, strongly influence the dynamics of body formation. Particularly, it has been observed that more compact structures, such as sphere-like structures, are more likely to follow the claim of the size-complexity rule, whereas more fragile structures such as linear chains, which are more vulnerable to drastic changes due to division mechanisms, can, in a broad scenario, violate the size-complexity rule.}, } @article {pmid29119723, year = {2018}, author = {Suppan, J and Engel, B and Marchetti-Deschmann, M and Nürnberger, S}, title = {Tick attachment cement - reviewing the mysteries of a biological skin plug system.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {1056-1076}, pmid = {29119723}, issn = {1469-185X}, abstract = {The majority of ticks in the family Ixodidae secrete a substance anchoring their mouthparts to the host skin. This substance is termed cement. It has adhesive properties and seals the lesion during feeding. The particular chemical composition and the curing process of the cement are unclear. This review summarizes the literature, starting with a historical overview, briefly introducing the different hypotheses on the origin of the adhesive and how the tick salivary glands have been identified as its source. Details on the sequence of cement deposition, the curing process and detachment are provided. Other possible functions of the cement, such as protection from the host immune system and antimicrobial properties, are presented. Histochemical and ultrastructural data of the intracellular granules in the salivary gland cells, as well as the secreted cement, suggest that proteins constitute the main material, with biochemical data revealing glycine to be the dominant amino acid. Applied methods and their restrictions are discussed. Tick cement is compared with adhesives of other animals such as barnacles, mussels and sea urchins. Finally, we address the potential of tick cement for the field of biomaterial research and in particular for medical applications in future.}, } @article {pmid29119380, year = {2018}, author = {Konstantinov, KK and Konstantinova, AF}, title = {Chiral Symmetry Breaking in Peptide Systems During Formation of Life on Earth.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {93-122}, doi = {10.1007/s11084-017-9551-4}, pmid = {29119380}, issn = {1573-0875}, mesh = {Amino Acids/*chemistry ; Catalysis ; Kinetics ; Models, Theoretical ; *Origin of Life ; Peptides/*chemistry ; Stereoisomerism ; Thermodynamics ; }, abstract = {Chiral symmetry breaking in complex chemical systems with a large number of amino acids and a large number of similar reactions was considered. It was shown that effective averaging over similar reaction channels may result in very weak effective enantioselectivity of forward reactions, which does not allow most of the known models to result in chiral symmetry breaking during formation of life on Earth. Models with simple and catalytic synthesis of a single amino acid, formation of peptides up to length five, and sedimentation of insoluble pair of substances were considered. It was shown that depending on the model and the values of the parameters, chiral symmetry breaking may occur in up to about 10% out of all possible unique insoluble pair combinations even in the absence of any catalytic synthesis and that minimum total number of amino acids in the pair is 5. If weak enantioselective forward catalytic synthesis of amino acids is present, then the number of possible variants, in which chiral symmetry breaking may occur, increases substantially. It was shown that that the most interesting catalysts have zero or one amino acid of "incorrect" chirality. If the parameters of the model are adjusted in such a way to result in an increase of concentration of longer peptides, then catalysts with two amino acids of incorrect chirality start to appear at peptides of length five. Models of chiral symmetry breaking in the presence of epimerization were considered for peptides up to length three. It was shown that the range of parameters in which chiral symmetry breaking could occur significantly shrinks in comparison to previously considered models with peptides up to length two. An experiment of chiral symmetry breaking was proposed. The experiment consists of a three-step cycle: reversible catalytic synthesis of amino acids, reversible synthesis of peptides, and irreversible sedimentation of insoluble substances.}, } @article {pmid29119234, year = {2018}, author = {Liu, C and Han, C and Jiang, S and Zhao, X and Tian, Y and Yan, K and Wang, X and Xiang, W}, title = {Streptomyces lasii sp. nov., a Novel Actinomycete with Antifungal Activity Isolated from the Head of an Ant (Lasius flavus).}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {353-358}, pmid = {29119234}, issn = {1432-0991}, support = {31500010//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Antifungal Agents/chemistry/metabolism/*pharmacology ; Ants/*microbiology ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Head/microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Streptomyces/*chemistry/classification/*isolation & purification/metabolism ; }, abstract = {During a screening for novel and biotechnologically useful actinobacteria in insects, a novel actinobacteria with antifungal activity, designated strain 5H-CA11T, was isolated from the head of an ant (Lasius flavus) and characterized using a polyphasic approach. The organism was found to have morphological and chemotaxonomic characteristics typical of members of the genus Streptomyces. 16S rRNA gene sequence analysis showed that strain 5H-CA11T is a member of the genus Streptomyces, with the highest sequence similarity to Streptomyces scabrisporus DSM 41855T (98.9%). Similarities to other type strains of the genus Streptomyces were lower than 96%. Phylogenetic analysis based on the 16S rRNA gene sequence also indicated that strain 5H-CA11T clusters with S. scabrisporus DSM 41855T using two tree-making algorithms. DNA-DNA hybridization between strain 5H-CA11T and S. scabrisporus JCM 11712T revealed 33.6% similarity, supporting the phenotypic and phylogenetic differences found between these two strains. Therefore, the strain is concluded to represent a novel species of the genus Streptomyces, for which the name Streptomyces lasii sp. nov. is proposed. The type strain is 5H-CA11T (=CGMCC 4.7303T = DSM 102043T).}, } @article {pmid29119233, year = {2018}, author = {Baliga, P and Shekar, M and Venugopal, MN}, title = {Potential Outer Membrane Protein Candidates for Vaccine Development Against the Pathogen Vibrio anguillarum: A Reverse Vaccinology Based Identification.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {368-377}, pmid = {29119233}, issn = {1432-0991}, mesh = {Animals ; Bacterial Outer Membrane Proteins/chemistry/genetics/*immunology ; Bacterial Vaccines/chemistry/genetics/*immunology ; Epitope Mapping ; Epitopes, T-Lymphocyte/immunology ; Fish Diseases/immunology/microbiology/*prevention & control ; Fishes ; Vibrio/chemistry/genetics/*immunology ; Vibrio Infections/immunology/microbiology/*veterinary ; }, abstract = {Reverse vaccinology is a widely used approach that has facilitated the rapid identification of vaccine candidates suitable in vaccine development for pathogens. Vibrio anguillarum is a major pathogen responsible for vibriosis in fish and shellfish leading to huge economic losses to the aquaculture industry. Although commercial vaccines are available for fish against this bacterium they have their own limitations. In this study, we used the reverse vaccinology strategy to screen and identify V. anguillarum outer membrane proteins (OMPs) that could serve as vaccine candidates. Our analysis identified 23 antigenic outer membrane proteins which were highly conserved (>98% identity) across serovars of this bacterium. Of the 23, two were identified as outer membrane lipoproteins. Among the OMPs identified 18 were novel to this study and conserved across several Vibrio spp. with an identity of 21-93%. While the least (>48%) identity was observed for V. anguillarum ferrichrome-iron transporter protein, the highest identity (>80%) was seen for outer membrane proteins OmpK, BamA, OmpU, Fatty acid transporter, and two hypothetical proteins. These potential vaccine targets identified could contribute to the development of effective vaccine not only against V. anguillarum but also across other Vibrio spp. In addition, several B-cell and T-cell epitopes were predicted for the novel OMPs in this study which could aid in narrowing down peptide selection in designing a suitable epitope-based vaccine.}, } @article {pmid29117456, year = {2018}, author = {Coakley, CM and Nestoros, E and Little, TJ}, title = {Testing hypotheses for maternal effects in Daphnia magna.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {2}, pages = {211-216}, doi = {10.1111/jeb.13206}, pmid = {29117456}, issn = {1420-9101}, abstract = {Maternal effects are widely observed, but their adaptive nature remains difficult to describe and interpret. We investigated adaptive maternal effects in a clone of the crustacean Daphnia magna, experimentally varying both maternal age and maternal food and subsequently varying food available to offspring. We had two main predictions: that offspring in a food environment matched to their mothers should fare better than offspring in unmatched environments, and that offspring of older mothers would fare better in low food environments. We detected numerous maternal effects, for example offspring of poorly fed mothers were large, whereas offspring of older mothers were both large and showed an earlier age at first reproduction. However, these maternal effects did not clearly translate into the predicted differences in reproduction. Thus, our predictions about adaptive maternal effects in response to food variation were not met in this genotype of Daphnia magna.}, } @article {pmid29116346, year = {2018}, author = {Weilan, L and Lee, JJ and Lee, SY and Park, S and Ten, LN and Jung, HY}, title = {Spirosoma humi sp. nov., Isolated from Soil in South Korea.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {328-335}, pmid = {29116346}, issn = {1432-0991}, support = {Project No. PJ011631042017//Cooperative Research Program for Agriculture Science & Technology Development Rural Development Administration, Republic of Korea/ ; grant 162S-4-3-1727//Brain Pool Program of 2016 through the Korean Federation of Science and Technology Societies (KOFST) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea./ ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; Cytophagaceae/classification/genetics/*isolation & purification/metabolism ; DNA, Bacterial ; Fatty Acids/chemistry/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; *Soil Microbiology ; }, abstract = {A Gram-stain-negative, non-motile, rod-shaped, aerobic bacterial strain, designated S7-4-1T, was isolated from soil in Gyeongsangnam-do, South Korea and characterized using a polyphasic approach to determine its taxonomic position. Phylogenic analysis based on the 16S rRNA gene sequence showed that strain S7-4-1T belonged to the family Cytophagaceae and was most closely related to Spirosoma fluviale MSd3T (96.2%), 'Spirosoma radiotolerans' DG5A (96.0%), Spirosoma pulveris JSH5-14T (95.9%), and Spirosoma linguale DSM 74T (95.8%). The G+C content of the genomic DNA of the isolate was 49.0 mol%. The strain contained summed feature 3 (C16:1 ω7c/C16:1 ω6c; 41.0%), C16:1 ω5c (24.9%), and C15:0 iso (9.3%) as the major fatty acids, menaquinone MK-7 as the predominant respiratory quinone, and phosphatidylethanolamine and an unidentified aminophospholipid as the main polar lipids, which supported its affiliation with the genus Spirosoma. The results of physiological and biochemical tests allowed the genotypic and phenotypic differentiation of the isolate from recognized Spirosoma species. On the basis of its phenotypic properties, genotypic distinctiveness, and chemotaxonomic features, strain S7-4-1T represents a novel species of the genus Spirosoma, for which the name Spirosoma humi sp. nov. is proposed. The type strain is S7-4-1T (= KCTC 52729T = JCM 32132T).}, } @article {pmid29116345, year = {2018}, author = {Laport, MS and Bauwens, M and Collard, M and George, I}, title = {Phylogeny and Antagonistic Activities of Culturable Bacteria Associated with the Gut Microbiota of the Sea Urchin (Paracentrotus lividus).}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {359-367}, pmid = {29116345}, issn = {1432-0991}, mesh = {Animals ; *Antibiosis ; Bacteria/*classification/genetics/*isolation & purification ; Bacterial Physiological Phenomena ; Biodiversity ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; *Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Paracentrotus/*microbiology ; *Phylogeny ; }, abstract = {In this study, we have investigated the phylogeny and the antagonistic interactions of culturable bacteria isolated from the sea urchin Paracentrotus lividus collected from Aber and Morgat, both located in Crozon peninsula, France. Bacteria were isolated from the gastrointestinal tracts of ten specimens by using conventional culture-dependent method and then investigated by using phylogenetic analysis based on 16S rRNA gene sequence comparisons. Assays for antagonistic interactions among the bacterial strains were performed; bacteria (including at least one strain representative of each OTU identified) were screened for antimicrobial substance production. So, 367 bacterial strains were isolated on marine-agar. On the basis of morphological characteristics, 180 strains were sequenced and 94 OTUs were classified. The dominant phyla were Proteobacteria, Firmicutes and Actinobacteria, with a high abundance of the strains belonging to the genus Psychrobacter. From the antagonistic interactions assays, it could be determined that 22.7% strains were positive for at least one antagonism interaction, 18.3% of them isolated from the sea urchins collected in Morgat. We hypothesize that the bacteria isolated in this study may represent the transitory microbiota of the gastrointestinal tract of P. lividus, and that this microbiota may be related to the diet of this marine invertebrate. Furthermore, our results suggest that chemical antagonism could play a significant role in shaping the bacterial communities within gastrointestinal tract of the sea urchins. In addition, most isolated bacteria may have promising biotechnology applications.}, } @article {pmid29116040, year = {2018}, author = {Pal, D and Bhardwaj, A and Kaur, N and Sudan, SK and Bisht, B and Kumari, M and Vyas, B and Krishnamurthi, S and Mayilraj, S}, title = {Fictibacillus aquaticus sp. nov., isolated from downstream river water.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {160-164}, doi = {10.1099/ijsem.0.002474}, pmid = {29116040}, issn = {1466-5034}, mesh = {Bacillaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; India ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Rivers/*microbiology ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, facultatively anaerobic bacterial strain, GDSW-R2A3T, was isolated from a downstream water sample collected from the river Ganges, India. Analysis of the 16S rRNA gene sequence of strain GDSW-R2A3T revealed its affiliation to the family Bacillaceae. Further analysis using a polyphasic approach revealed that strain GDSW-R2A3T was most closely related to the genus Fictibacillus. Analysis of the almost-complete (1488 bp) 16S rRNA gene sequence of strain GDSW-R2A3T revealed the highest level of sequence similarity with Fictibacillus phosphorivorans CCM 8426T (98.3 %) and Fictibacillus nanhaiensis KCTC 13712T (98.3 %) followed by Fictibacillus barbaricus DSM 14730T (98.0 %). The digital DNA-DNA hybridization and average nucleotide identity (ANI) values between strain GDSW-R2A3T and the most closely related taxon, F. phosphorivorans CCM 8426T, were 20.3 and 78.2 %, respectively. The DNA G+C content of the strain was 44.2 mol%. The cell-wall amino acid was meso-diaminopimelic acid. Polar lipids present were phosphatidylglycerol, phosphatidylethanolamine, diphosphatidylglycerol, three aminophospholipids, two phospholipids and one unidentified lipid; the major menaquinone was MK-7; iso-C14 : 0, iso-C15 : 0 and anteiso-C15 : 0 were the major fatty acids. On the basis of the phenotypic, chemotaxonomic and phylogenetic data, it can be concluded that strain GDSW-R2A3T represents a novel species of the genus Fictibacillus, for which the name Fictibacillus aquaticus sp. nov. is proposed. The type strain is GDSW-R2A3T (=VTCC-B-910015T=CCM 8782T).}, } @article {pmid29116039, year = {2018}, author = {Lin, SY and Hameed, A and Hsu, YH and Liu, YC and Hung, MH and Lai, WA and Young, CC}, title = {Sphingomonas colocasiae sp. nov., isolated from taro (Colocasia esculanta).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {133-140}, doi = {10.1099/ijsem.0.002471}, pmid = {29116039}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Colocasia/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Spermidine/analogs & derivatives/chemistry ; Sphingomonas/*classification/genetics/isolation & purification ; Taiwan ; Ubiquinone/chemistry ; }, abstract = {A polyphasic approach was used to characterize an aerobic, Gram-stain-negative, rod-shaped bacterium (designed as strain CC-MHH0539T) isolated from the chopped tuber of taro (Colocasia esculanta) in Taiwan. Strain CC-MHH0539T was able to grow at 15-30 °C (optimum, 25 °C), at pH 6.0-9.0 (optimum, 7.0) and with 0-1 % (w/v) NaCl. Strain CC-MHH0539T showed highest 16S rRNA gene sequence similarity to Sphingomonas laterariae LNB2T (96.8 %), Sphingobium boeckii 469T (96.5 %), Sphingomonas faucium E62-3T (96.4 %) and Sphingosinicella vermicomposti YC7378T (96.2 %) and <96.1 % similarity to other sphingomonads. Strain CC-MHH0539T was found to cluster mainly with the clade that accommodated members of the genus Sphingomonas. The dominant cellular fatty acids were C16 : 0, C16 : 1ω5c, C14 : 0 2-OH, C16 : 1ω7c/C16 : 1ω6c and C18 : 1ω7c/C18 : 1ω6c. Diphosphatidylglycerol, phosphatidylglycerol, phosphatidylcholine, phosphatidylethanolamine, phosphatidylmonomethylethanolamine, two sphingoglycolipids and two unidentified phospholipids were detected in strain CC-MHH0539T. The DNA G+C content was 69.5 mol%. The respiratory quinone system and predominant polyamine was ubiquinone 10 (Q-10) and sym-homospermidine, respectively, which is in line with Sphingomonas representatives. Based on the distinct phylogenetic, phenotypic and chemotaxonomic traits, strain CC-MHH0539T is considered to represent a novel species of the genus Sphingomonas, for which the name Sphingomonas colocasiae sp. nov. is proposed. The type strain is CC-MHH0539T (=BCRC 80933T=JCM 31229T).}, } @article {pmid29116036, year = {2018}, author = {Modesto, M and Michelini, S and Sansosti, MC and De Filippo, C and Cavalieri, D and Qvirist, L and Andlid, T and Spiezio, C and Sandri, C and Pascarelli, S and Sgorbati, B and Mattarelli, P}, title = {Bifidobacterium callitrichidarum sp. nov. from the faeces of the emperor tamarin (Saguinus imperator).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {141-148}, doi = {10.1099/ijsem.0.002472}, pmid = {29116036}, issn = {1466-5034}, mesh = {Aldehyde-Lyases/chemistry ; Animals ; Bacterial Typing Techniques ; Base Composition ; Bifidobacterium/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Feces/microbiology ; Multilocus Sequence Typing ; Peptidoglycan/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Saguinus/*microbiology ; Sequence Analysis, DNA ; }, abstract = {Three Gram-stain-positive, non-spore-forming, microaerophilic and fructose-6-phosphate phosphoketolase positive strains were isolated from a faecal sample of an adult subject of the emperor tamarin (Saguinus imperator). Given that the isolates revealed identical BOX PCR profiles, strain TRI 5T was selected as a representative and characterized further. Comparative analysis of 16S rRNA gene sequence similarity revealed that strain TRI 5T was closely related to Bifidobacterium saguini DSM 23967T (96.4 %) and to Bifidobacterium longum subsp. longum ATCC 15708 (96.2 %). Multilocus sequence analyses of five housekeeping genes showed the close phylogenetic relatedness of this strain to Bifidobacterium breve DSM 20213T (hsp60 94.1 %), Bifidobacterium saguini DSM 23967T (clpC 91 %), Bifidobacterium avesanii DSM 100685T (dnaG 80.3 %), Bifidobacterium longumsubsp. infantis ATCC 15697T (dnaJ 85.3 %) and Bifidobacterium longumsubsp. longum ATCC 15708 (rpoB 93 %), respectively. The peptidoglycan type was A3β, with an interpeptide bridge comprising l-Orn (Lys) - l-Ser - l-Ala - l-Thr - l-Ala. The DNA G+C content of strain TRI 5T was 60.9 mol%. Based on the data provided, strain TRI 5T represents a novel species of the genus Bifidobacterium for which the name Bifidobacteriumcallitrichidarum sp. nov. is proposed. The type strain is TRI 5T (=DSM 103152T=JCM 31790T).}, } @article {pmid29116035, year = {2018}, author = {Dai, YM and Zhang, LL and Li, Y and Li, YQ and Deng, XH and Wang, TT and Yang, F and Tian, YQ and Li, N and Zhou, XM and Liu, XF and Li, WJ}, title = {Characterization of Trichococcus paludicola sp. nov. and Trichococcus alkaliphilus sp. nov., isolated from a high-elevation wetland, by phenotypic and genomic analyses.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {99-105}, doi = {10.1099/ijsem.0.002464}, pmid = {29116035}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Carnobacteriaceae/*classification/genetics/isolation & purification ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Wetlands ; }, abstract = {Two psychrotolerant facultative anaerobes, strains B7-2T and B5T, were isolated from the Zoige Wetland on the Qinghai-Tibetan Plateau. The 16S rRNA gene sequences of strains B7-2T and B5T shared high similarity (>99 %) with those of the type strains of the genus Trichococcus, while their digital DNA-DNA hybridization values with each other (49 %) and with the reference type strains (48-23 %) were lower than 70 %, which suggest that they represent two novel species of the genus Trichococcus. Cells of strains B7-2T and B5T were immotile cocci, grew in the temperature range of 4-37 °C (optimum 25 °C) and were alkaliphilic with optimum growth at pH 9.0. The major components of the cellular fatty acids were C16 : 0, anteiso-C17 : 0 and C18 : 0 for strain B7-2T, and C16 : 0, anteiso-C17 : 0, C18 : 1ω9c and C18 : 0 for strain B5T. The genomic DNA G+C contents were 46.0 and 46.7 mol% for strains B7-2T and B5T, respectively. Based on physiological and genomic characteristics, it is suggested that strains B7-2T and B5T represent two novel species within the genus Trichococcus, for which the names Trichococcus paludicola sp. nov. and Trichococcus alkaliphilus sp. nov. are proposed. The type strains are B7-2T (=DSM 104691T=KCTC 33886T) and B5T (=DSM 104692T=KCTC 33885T), respectively.}, } @article {pmid29116034, year = {2018}, author = {Lin, SY and Hameed, A and Hsieh, YT and Hsu, YH and Lai, WA and Young, CC}, title = {Castellaniella fermenti sp. nov., isolated from a fermented meal.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {52-57}, doi = {10.1099/ijsem.0.002436}, pmid = {29116034}, issn = {1466-5034}, mesh = {Alcaligenaceae/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Fermented Foods/*microbiology ; *Food Microbiology ; Phospholipids/chemistry ; *Phylogeny ; Putrescine/chemistry ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Taiwan ; Ubiquinone/chemistry ; }, abstract = {A polyphasic taxonomic approach was used to characterize a presumably novel bacterium, designated strain CC-YTH191T, isolated from a fermented meal in Taiwan. Cells of strain CC-YTH191T were Gram-stain-negative aerobic rods, which grew at 15-40 °C (optimal 25-30 °C), pH 6.0-9.0 (optimal 7.0) and 1-2 % (w/v) NaCl (optimal 1 %). On the basis of 16S rRNA gene sequence analysis, strain CC-YTH191T appeared to belong to the genus Castellaniella, and was closely related to Castellaniella hirudinis (96.7 % similarity), Castellaniella ginsengisoli (96.7 %) and Castellaniella caeni (96.0 %), while with other related species it shared <96.0 % similarity. The major cellular fatty acids of the isolate were C16 : 0, C17 : 0cyclo, C14 : 0 3OH/C16 : 1iso I and C18 : 1ω7c/C18 : 1ω6c. The polar lipid profile contained diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine, phosphatidylserine, three unidentified phospholipids, an unidentified aminolipid and an unidentified aminophospholpid. Putrescine was the predominant polyamine followed by spermidine. The DNA G+C content was 62.2 mol% and the predominant quinone system was ubiquinone 8 (Q-8). All these features confirmed the placement of the strain CC-YTH191T as a novel species within the genus Castellaniella, for which the name Castellaniella fermenti sp. nov. is proposed. The type strain is CC-YTH191T (=BCRC 81023T=JCM 31755T).}, } @article {pmid29116033, year = {2018}, author = {Choi, GM and Lee, SY and Choi, KD and Im, WT}, title = {Phenylobacterium hankyongense sp. nov., isolated from ginseng field soil.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {125-130}, doi = {10.1099/ijsem.0.002469}, pmid = {29116033}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Caulobacteraceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Panax/*microbiology ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; *Soil Microbiology ; Transferases (Other Substituted Phosphate Groups)/chemistry ; Ubiquinone/chemistry ; }, abstract = {A Gram-stain-negative, aerobic, non-motile, non-spore-forming and rod-shaped bacterial strain, designated HKS-05T, was isolated from ginseng field soil. This bacterium was characterized to determine its taxonomic position by using the polyphasic approach. HKS-05T grew at 10-37 °C and at pH 6.0-8.0 on R2A agar. On the basis of 16S rRNA gene sequence similarity, HKS-05T was shown to represent a member of the family Caulobacteraceaeand to be related to Phenylobacterium lituiforme FaiI3T (98.1 % sequence similarity), 'Phenylobacterium zucineum' HLK1 (97.9 %), Phenylobacterium muchangponense A8T (97.7 %), Phenylobacteriumcomposti 4T-6T (97.2 %) and Phenylobacterium immobile ET (97.1 %). The major respiratory quinone was Q-10 and the major fatty acids were summed feature 8 (comprising C18 : 1ω7c and/or C18 : 1ω6c), C16 : 0, and summed feature 3 (comprising C16 : 1ω7c and/or C16 : 1ω6c). The polar lipids were phosphatidylglycerol, unidentified glycolipids and unidentified polar lipids. The G+C content of the genomic DNA was 70.4 mol%. DNA-DNA relatedness values between HKS-05T and its closest phylogenetically neighbours were low. HKS-05T could be differentiated genotypically and phenotypically from the species of the genus Phenylobacterium with validly published names. The isolate therefore represents a novel species, for which the name Phenylobacteriumhankyongense sp. nov. is proposed, with the type strain HKS-05T (=KACC 18628T=LMG 30081T).}, } @article {pmid29115026, year = {2018}, author = {Rolls, RJ and Heino, J and Ryder, DS and Chessman, BC and Growns, IO and Thompson, RM and Gido, KB}, title = {Scaling biodiversity responses to hydrological regimes.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {971-995}, doi = {10.1111/brv.12381}, pmid = {29115026}, issn = {1469-185X}, abstract = {Of all ecosystems, freshwaters support the most dynamic and highly concentrated biodiversity on Earth. These attributes of freshwater biodiversity along with increasing demand for water mean that these systems serve as significant models to understand drivers of global biodiversity change. Freshwater biodiversity changes are often attributed to hydrological alteration by water-resource development and climate change owing to the role of the hydrological regime of rivers, wetlands and floodplains affecting patterns of biodiversity. However, a major gap remains in conceptualising how the hydrological regime determines patterns in biodiversity's multiple spatial components and facets (taxonomic, functional and phylogenetic). We synthesised primary evidence of freshwater biodiversity responses to natural hydrological regimes to determine how distinct ecohydrological mechanisms affect freshwater biodiversity at local, landscape and regional spatial scales. Hydrological connectivity influences local and landscape biodiversity, yet responses vary depending on spatial scale. Biodiversity at local scales is generally positively associated with increasing connectivity whereas landscape-scale biodiversity is greater with increasing fragmentation among locations. The effects of hydrological disturbance on freshwater biodiversity are variable at separate spatial scales and depend on disturbance frequency and history and organism characteristics. The role of hydrology in determining habitat for freshwater biodiversity also depends on spatial scaling. At local scales, persistence, stability and size of habitat each contribute to patterns of freshwater biodiversity yet the responses are variable across the organism groups that constitute overall freshwater biodiversity. We present a conceptual model to unite the effects of different ecohydrological mechanisms on freshwater biodiversity across spatial scales, and develop four principles for applying a multi-scaled understanding of freshwater biodiversity responses to hydrological regimes. The protection and restoration of freshwater biodiversity is both a fundamental justification and a central goal of environmental water allocation worldwide. Clearer integration of concepts of spatial scaling in the context of understanding impacts of hydrological regimes on biodiversity will increase uptake of evidence into environmental flow implementation, identify suitable biodiversity targets responsive to hydrological change or restoration, and identify and manage risks of environmental flows contributing to biodiversity decline.}, } @article {pmid29114986, year = {2018}, author = {Fountain-Jones, NM and Pearse, WD and Escobar, LE and Alba-Casals, A and Carver, S and Davies, TJ and Kraberger, S and Papeş, M and Vandegrift, K and Worsley-Tonks, K and Craft, ME}, title = {Towards an eco-phylogenetic framework for infectious disease ecology.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {950-970}, doi = {10.1111/brv.12380}, pmid = {29114986}, issn = {1469-185X}, abstract = {Identifying patterns and drivers of infectious disease dynamics across multiple scales is a fundamental challenge for modern science. There is growing awareness that it is necessary to incorporate multi-host and/or multi-parasite interactions to understand and predict current and future disease threats better, and new tools are needed to help address this task. Eco-phylogenetics (phylogenetic community ecology) provides one avenue for exploring multi-host multi-parasite systems, yet the incorporation of eco-phylogenetic concepts and methods into studies of host pathogen dynamics has lagged behind. Eco-phylogenetics is a transformative approach that uses evolutionary history to infer present-day dynamics. Here, we present an eco-phylogenetic framework to reveal insights into parasite communities and infectious disease dynamics across spatial and temporal scales. We illustrate how eco-phylogenetic methods can help untangle the mechanisms of host-parasite dynamics from individual (e.g. co-infection) to landscape scales (e.g. parasite/host community structure). An improved ecological understanding of multi-host and multi-pathogen dynamics across scales will increase our ability to predict disease threats.}, } @article {pmid29113924, year = {2018}, author = {Léveillé-Bourret, É and Starr, JR and Ford, BA}, title = {Why are there so many sedges? Sumatroscirpeae, a missing piece in the evolutionary puzzle of the giant genus Carex (Cyperaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {93-104}, doi = {10.1016/j.ympev.2017.10.025}, pmid = {29113924}, issn = {1095-9513}, mesh = {Carex Plant/anatomy & histology/*classification ; Fossils ; Likelihood Functions ; *Phylogeny ; }, abstract = {For over a century, the origins and mechanisms underlying the diversification of the enormous temperate genus Carex (>2100 species; Cariceae, Cyperaceae) have remained largely speculative. Characteristics such as its diverse ecology, varied biogeography, and intriguing cytology have made Carex a powerful model for studying plant evolution, but its uncertain sister-group relationships hinder its use in studies that depend on accurate ancestral state estimates and biogeographic inferences. To identify the sister to Carex, we estimated the phylogeny of all genera in the Cariceae-Dulichieae-Scirpeae clade (CDS) using three plastid and two nuclear ribosomal markers. Ancestral state reconstructions of key characters were made, and a time-calibrated tree estimated. Carex is strongly supported as sister to the rare East Asian Sumatroscirpus, sole genus of a new tribe, Sumatroscirpeae trib. nov. Believed to be unique to Carex, the perigynium (prophyllar bract enclosing a flower) is in fact a synapomorphy shared with this small tribe (∼4 species) that appeared 36 Mya. We thus suggest the initial key innovation in the remarkable diversification of Carex is not the perigynium, but could be the release of mechanical constraints on perigynia through spikelet truncation, resulting in novel adaptive morphologies. Monoecy, chromosomal change, and rapid inflorescence development enabling phenological isolation may also be involved. The tiny tribe Sumatroscirpeae will provide unprecedented insights into the inflorescence homology, evolution, diversification, and biogeographic history of its sister-group Carex, one of the world's most diverse plant lineages.}, } @article {pmid29113919, year = {2018}, author = {Elgamoudi, BA and Ketley, JM}, title = {Lighting up my life: a LOV-based fluorescent reporter for Campylobacter jejuni.}, journal = {Research in microbiology}, volume = {169}, number = {2}, pages = {108-114}, doi = {10.1016/j.resmic.2017.10.003}, pmid = {29113919}, issn = {1769-7123}, mesh = {Bacterial Proteins/chemistry/genetics/metabolism ; Campylobacter jejuni/*chemistry/*genetics/metabolism/radiation effects ; Fluorescence ; Genes, Reporter ; Light ; Luminescent Measurements/*methods ; Microscopy, Fluorescence ; Oxygen/*metabolism ; Plasmids/genetics/metabolism ; Promoter Regions, Genetic ; }, abstract = {In this study, a LOV-based fluorescent reporter (light, oxygen, or voltage-sensing domains of phototropin), termed iLOV, was adapted for Campylobacter jejuni and used to investigate promoter activity via monitoring fluorescence intensity and to study the localisation of two chemotaxis proteins. The pC46 complementation vector contains coding sequence from cj0046, a C. jejuni NCTC11168 pseudo-gene and is used to integrate cloned genes onto the C. jejuni chromosome. The pC46 vector was used to construct plasmids containing iLOV, driven by three different C. jejuni constitutive promoters and plasmids containing transcriptional fusions of the iLOV reporter and two chemoreceptors, tlp5 and tlp8. Expression from the porA promoter, pporA, produced the highest fluorescence signals compared to pfdxA (intermediate level) and pmetK (lowest level). The cellular localisation pattern of transducer-like protein (Tlp) clusters, containing Tlp5 and Tlp8, was predominately polar, with Tlp5 positioned only at one and Tlp8 at both poles. Here, we demonstrate that a iLOV fluorescent reporter can be used as a promoter probe or as a gene fusion reporter in Campylobacter spp. This is a new system uniquely placed for studying Campylobacter spp., as it combines resistance to photobleaching and functionality under microaerobic conditions.}, } @article {pmid29113748, year = {2018}, author = {Forecki, J and Van Antwerp, DJ and Lujan, SM and Merzdorf, CS}, title = {Roles for Xenopus aquaporin-3b (aqp3.L) during gastrulation: Fibrillar fibronectin and tissue boundary establishment in the dorsal margin.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {3-16}, doi = {10.1016/j.ydbio.2017.11.001}, pmid = {29113748}, issn = {1095-564X}, mesh = {Animals ; Aquaporin 3/*metabolism/*physiology ; Aquaporins/metabolism/physiology ; Cell Movement ; Ectoderm ; Fibronectins/genetics/metabolism ; Gastrula/physiology ; Gastrulation/physiology ; Gene Expression Profiling ; Membrane Cofactor Protein ; Mesoderm/cytology ; Morphogenesis ; Xenopus laevis/embryology/physiology ; }, abstract = {Aquaporins and aquaglyceroporins are a large family of membrane channel proteins that allow rapid movement of water and small, uncharged solutes into and out of cells along concentration gradients. Recently, aquaporins have been gaining recognition for more complex biological roles than the regulation of cellular osmotic homeostasis. We have identified a specific expression pattern for Xenopus aqp3b (also called aqp3.L) during gastrulation, where it is localized to the sensorial (deep) layer of the blastocoel roof and dorsal margin. Interference with aqp3b expression resulted in loss of fibrillar fibronectin matrix in Brachet's cleft at the dorsal marginal zone, but not on the free surface of the blastocoel. Detailed observation showed that the absence of fibronectin matrix correlated with compromised border integrities between involuted mesendoderm and noninvoluted ectoderm in the marginal zone. Knockdown of aqp3b also led to delayed closure of the blastopore, suggesting defects in gastrulation movements. Radial intercalation was not affected in aqp3b morphants, while the data presented are consistent with impeded convergent extension movements of the dorsal mesoderm in response to loss of aqp3b. Our emerging model suggests that aqp3b is part of a mechanism that promotes proper interaction between cells and the extracellular matrix, thereby playing a critical role in gastrulation.}, } @article {pmid29113696, year = {2018}, author = {Nylin, S and Agosta, S and Bensch, S and Boeger, WA and Braga, MP and Brooks, DR and Forister, ML and Hambäck, PA and Hoberg, EP and Nyman, T and Schäpers, A and Stigall, AL and Wheat, CW and Österling, M and Janz, N}, title = {Embracing Colonizations: A New Paradigm for Species Association Dynamics.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {1}, pages = {4-14}, doi = {10.1016/j.tree.2017.10.005}, pmid = {29113696}, issn = {1872-8383}, mesh = {Animals ; *Host-Parasite Interactions ; Insecta/parasitology/physiology ; Invertebrates/*parasitology/*physiology ; Parasitology ; Plants/parasitology ; Species Specificity ; Vertebrates/*parasitology/*physiology ; }, abstract = {Parasite-host and insect-plant research have divergent traditions despite the fact that most phytophagous insects live parasitically on their host plants. In parasitology it is a traditional assumption that parasites are typically highly specialized; cospeciation between parasites and hosts is a frequently expressed default expectation. Insect-plant theory has been more concerned with host shifts than with cospeciation, and more with hierarchies among hosts than with extreme specialization. We suggest that the divergent assumptions in the respective fields have hidden a fundamental similarity with an important role for potential as well as actual hosts, and hence for host colonizations via ecological fitting. A common research program is proposed which better prepares us for the challenges from introduced species and global change.}, } @article {pmid29112885, year = {2018}, author = {Neville, BA and Forster, SC and Lawley, TD}, title = {Commensal Koch's postulates: establishing causation in human microbiota research.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {47-52}, doi = {10.1016/j.mib.2017.10.001}, pmid = {29112885}, issn = {1879-0364}, support = {//Wellcome Trust/United Kingdom ; }, mesh = {Gastrointestinal Microbiome/genetics/physiology ; Humans ; Metagenomics/methods ; *Microbiota ; Research ; *Symbiosis ; }, abstract = {Advances in high-throughput sequencing technologies and the development of sophisticated bioinformatics analysis methods, algorithms, and pipelines to handle the large amounts of data generated have driven the field of human microbiome research forward. This specialist knowledge has been crucial to thoroughly mine the human gut microbiota, particularly in the absence of methods for the routine cultivation of most enteric microorganisms. In recent years, however, significant efforts have been made to address the 'great plate count anomaly' and to overcome the barriers to cultivation of the fastidious and mostly strictly anaerobic bacteria that reside in the human gut. As a result, many new species have been discovered, characterised, genome sequenced, and deposited in culture collections. These continually expanding resources enable experimental investigation of the human gut microbiota, validation of hypotheses made with sequence-based analyses, and phenotypic characterisation of its constituent microbes. Herein we propose a variant of Koch's postulates, aimed at providing a framework to establish causation in microbiome studies, with a particular focus on demonstrating the health-promoting role of the commensal gut microbiota.}, } @article {pmid29112768, year = {2018}, author = {Grossi, PA and Percivalle, E and Campanini, G and Sarasini, A and Premoli, M and Zavattoni, M and Girello, A and Dalla Gasperina, D and Balsamo, ML and Baldanti, F and Rovida, F}, title = {An autochthonous sexually transmitted Zika virus infection in Italy 2016.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {80-82}, pmid = {29112768}, issn = {1121-7138}, mesh = {Antibodies, Viral/blood ; Female ; Humans ; Italy/epidemiology ; Male ; Middle Aged ; Sexually Transmitted Diseases, Viral/*epidemiology ; Zika Virus/*immunology ; Zika Virus Infection/epidemiology/*transmission/virology ; }, abstract = {We describe two cases of Zika virus infection involving an Italian patient returning from the Dominican Republic and his wife, who remained in Italy and had not travelled to Zika virus endemic areas in the previous months. The infection was transmitted through unprotected sexual intercourse after the man's return to Italy.}, } @article {pmid29112767, year = {2018}, author = {Brunetti, G and Ceccarelli, G and Giordano, A and Navazio, AS and Vittozzi, P and Venditti, M and Raponi, G}, title = {Fast and reliable diagnosis of XDR Acinetobacter baumannii meningitis by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {77-79}, pmid = {29112767}, issn = {1121-7138}, mesh = {Acinetobacter Infections/cerebrospinal fluid/*diagnosis/microbiology ; Acinetobacter baumannii/*drug effects ; Anti-Bacterial Agents/administration & dosage/therapeutic use ; Colistin/administration & dosage/therapeutic use ; Drug Resistance, Multiple, Bacterial ; Female ; Humans ; Meningitis, Bacterial/cerebrospinal fluid/*microbiology ; Middle Aged ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization/methods ; }, abstract = {Bacterial meningitis is a medical emergency needing quick and timely diagnosis. Even though meningitis caused by Acinetobacter baumannii is relatively rare, it is associated with high mortality rates especially in neurosurgery patients and represents a serious therapeutic problem due to the limited penetration of effective antibiotics into the cerebrospinal fluid. Recently, matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF) has been effectively used as a rapid method for microbial identification. In this case report we identified A. baumanni by MALDI-TOF technique directly from the CSF drawn from the external ventricular drainage of a patient with severe confusional state and signs of meningism. Simultaneously the antibiotic susceptibility test was performed by automated method from the pellet of the broth-enriched sample. The MALDI-TOF technique allowed microbial identification in less than 30 minutes, and the susceptibility test result was available in eight hours, thus allowing a fast diagnosis ready for prompt and targeted antimicrobial therapy.}, } @article {pmid29112766, year = {2018}, author = {Biava, M and Caglioti, C and Castilletti, C and Bordi, L and Carletti, F and Colavita, F and Quartu, S and Nicastri, E and Iannetta, M and Vairo, F and Liuzzi, G and Taglietti, F and Ippolito, G and Capobianchi, MR and Lalle, E}, title = {Persistence of ZIKV-RNA in the cellular fraction of semen is accompanied by a surrogate-marker of viral replication. Diagnostic implications for sexual transmission.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {30-33}, pmid = {29112766}, issn = {1121-7138}, mesh = {Adult ; Animals ; Biomarkers ; Cercopithecus aethiops ; Humans ; Male ; RNA, Viral/*isolation & purification ; Semen/*virology ; Vero Cells ; Virus Replication/*physiology ; Zika Virus/*isolation & purification ; Zika Virus Infection/*transmission/*virology ; }, abstract = {As asymptomatic infections represent 80% of ZIKV-infected individuals, sexual transmission is a rising concern. Recent studies highlighted a preferential association of ZIKV with the cellular fraction (CF) of different specimen types. Our aim was to evaluate the presence of ZIKV-RNA in different body fluids, focusing on semen specimens to assess the ZIKV-RNA content in either the unfractionated sample, its CF or seminal plasma (SP). In addition, to establish if the presence of ZIKV genome was associated with active virus replication, we measured the levels of negative-strand ZIKV-RNA. ZIKV total-RNA was detected in blood, urine and unfractionated semen, and neg-RNA in semen CF and SP samples longitudinally collected from two ZIKV-positive men followed at the National Institute for Infectious Diseases "L. Spallanzani", Italy. In both patients, ZIKV total-RNA was detected in CF with ct values always lower than in the corresponding unfractionated samples, and was observed even in the CF from negative unfractionated semen samples. In Patient 2, neg-RNA was also detected in CF, suggesting ongoing viral replication. Our results demonstrate higher clinical sensitivity of CF as compared to whole semen testing, emphasizing the need to extend ZIKV-RNA testing to CF, to rule out virus presence and the possible risk of sexual transmission.}, } @article {pmid29112765, year = {2018}, author = {Buonomo, AR and Scotto, R and Pinchera, B and Coppola, N and Monari, C and Macera, M and Borgia, G and Gentile, I}, title = {Epidemiology and risk factors for hepatitis C virus genotypes in a high prevalence region in Italy.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {26-29}, pmid = {29112765}, issn = {1121-7138}, mesh = {Aged ; *Genotype ; Hepacivirus/*genetics ; Hepatitis C/*epidemiology/*virology ; Humans ; Italy/epidemiology ; Middle Aged ; Multivariate Analysis ; Prevalence ; Risk Factors ; }, abstract = {Hepatitis C virus (HCV) is globally widespread. Southern Italy is a high prevalence region where the distribution of the HCV genotypes (GTs) is changing. Intravenous drug abuse is the only risk factor associated with a specific HCV GT (GT3). The aim of this study was to evaluate the distribution and the risk factors for specific HCV GTs. A total of 682 patients with measurable serum HCV-RNA were enrolled between January and March 2017. We recorded clinical information and the presence of risk factors for HCV. GT1b was the prevalent genotype in our patients (59.8%). HCV GT1a and GT3 infections were more frequent among patients aged ≤60 years (14.9% vs 2.2%, p<0.01 and 13.6% vs 0.8%, p<0.01, respectively). At multivariate analysis, intravenous drug abuse and age ≤60 years were associated with GT1a infection (OR: 4.79; 95% CI: 2.43-9.47, p <0.001 and OR: 5.07; 95CI: 2.25-11.40, p<0.001, respectively), while age ≤60 years was the only risk factor for GT3 (OR: 15.81; 95CI: 4.76-52.54, p <0.001). In the Campania region, we observed an increase in GT1a and GT3 rates compared with those observed in previous years. Age ≤60 was an independent risk factor for GT1a and GT3 infection. Intravenous drug use was independently associated with GT1a infection.}, } @article {pmid29111972, year = {2018}, author = {Jiang, S and Piao, C and Yu, Y and Cao, P and Li, C and Yang, F and Li, M and Xiang, W and Liu, C}, title = {Streptomyces capitiformicae sp. nov., a novel actinomycete producing angucyclinone antibiotics isolated from the head of Camponotus japonicus Mayr.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {118-124}, doi = {10.1099/ijsem.0.002468}, pmid = {29111972}, issn = {1466-5034}, mesh = {Animals ; Anthraquinones/*metabolism ; Anti-Bacterial Agents/biosynthesis ; Ants/*microbiology ; Bacterial Typing Techniques ; Base Composition ; China ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptomyces/*classification/genetics/isolation & purification ; }, abstract = {A novel actinomycete, designated strain 1H-SSA4T, was isolated from the head of an ant (Camponotus japonicus Mayr) and was found to produce angucyclinone antibiotics. A polyphasic approach was used to determine the taxonomic status of strain 1H-SSA4T. The DNA G+C content of the draft genome sequence, consisting of 11.4 Mbp, was 70.0 mol%. 16S rRNA gene sequence similarity studies showed that strain 1H-SSA4T belongs to the genus Streptomyces with the highest sequence similarity to Streptomyces hygroscopicus subsp. ossamyceticus NBRC 13983T (98.9 %), and phylogenetically clustered with this species, Streptomyces torulosus LMG 20305T (98.8 %), Streptomyces ipomoeae NBRC 13050T (98.5 %) and Streptomyces decoyicus NRRL 2666T (98.4 %). The morphological and chemotaxonomic properties of the strain were also consistent with those members of the genus Streptomyces. A combination of DNA-DNA hybridization experiments and phenotypic tests were carried out between strain 1H-SSA4T and the above-mentioned strains, which further clarified their relatedness and demonstrated that strain 1H-SSA4T could be distinguished from these strains. Therefore, the strain is concluded to represent a novel species of the genus Streptomyces, for which the name Streptomyces capitiformicae sp. nov. is proposed. The type strain is 1H-SSA4T (=CGMCC 4.7403T=DSM 104537T).}, } @article {pmid29111971, year = {2018}, author = {Hayashi, K and Busse, HJ and Golke, J and Anderson, J and Wan, X and Hou, S and Chain, PSG and Prescott, RD and Donachie, SP}, title = {Rheinheimera salexigens sp. nov., isolated from a fishing hook, and emended description of the genus Rheinheimera.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {35-41}, doi = {10.1099/ijsem.0.002412}, pmid = {29111971}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Chromatiaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Hawaii ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Sequence Analysis, DNA ; Ubiquinone/*chemistry ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-negative, rod-shaped bacterium, designated KH87T, was isolated from a fishing hook that had been baited and suspended in seawater off O'ahu, Hawai'i. Based on a comparison of 1524 nt of the 16S rRNA gene sequence of strain KH87T, its nearest neighbours were the GammaproteobacteriaRheinheimera nanhaiensis E407-8T (96.2 % identity), Rheinheimera chironomi K19414T (96.0 %), Rheinheimera pacifica KMM 1406T (95.8 %), Rheinheimera muenzenbergensis E49T (95.7 %), Alishewanella solinquinati KMK6T (94.9 %) and Arsukibacterium ikkense GCM72T (94.6 %). Cells of KH87T were motile by a single polar flagellum, strictly aerobic, and catalase- and oxidase-positive. Growth occurred between 4 and 39 °C, and in a circumneutral pH range. Major fatty acids in whole cells of strain KH87T were cis-9-hexadecenoic acid, hexadecanoic acid and cis-11-octadecenoic acid. The quinone system contained mostly menaquinone MK-7, and a minor amount of ubiquinone Q-8. The polar lipid profile contained the major lipids phosphatidylglycerol, phosphatidylserine, phosphatidylethanolamine, an unidentified aminolipid, and a lipid not containing phosphate, an amino group or a sugar moiety. Putrescine was the major polyamine. Physiological, biochemical and genomic data, including obligate halophily, absence of amylolytic activity, a quinone system dominated by MK-7 and DNA G+C content (42.0 mol%) distinguished KH87T from extant Rheinheimera species; strain KH87T was also distinguished by a multi-locus sequence analysis of aligned and concatenated 16S rRNA, gyrB, rpoB and rpoD gene sequences. Based on phenotypic and genotypic differences, the species Rheinheimera salexigens sp. nov. is proposed to accommodate KH87T as the type strain (=ATCC BAA-2715T=CIP 111115T). An emended description of the genus Rheinheimera is also proposed.}, } @article {pmid29111968, year = {2018}, author = {Kim, JY and Park, SH and Lee, DH and Song, G and Kim, YJ}, title = {Melaminivora jejuensis sp. nov., isolated from Swinery waste.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {9-13}, doi = {10.1099/ijsem.0.002294}, pmid = {29111968}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Comamonadaceae/*classification/genetics/isolation & purification ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Manure/*microbiology ; Nucleic Acid Hybridization ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Swine ; Ubiquinone/chemistry ; }, abstract = {A sulfur-oxidizing bacterium, designated strain KBB12T, was isolated from swinery waste collected in Jeju, Republic of Korea. The cells were Gram-stain-negative, flagellated and rod-shaped. Growth occurred at 15-45 °C (optimum, 30-37 °C), at pH 6-9 (optimum, pH 7.0) and in the presence of 0-1 % (w/v) NaCl. The major cellular fatty acids were summed feature 3 (iso-C15 : 0 2-OH and/or C16 : 1 ω7c, C16 : 0 and C18 : 1ω7c. The polar lipids were diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylglycerol, phospholipid and an unidentified lipid. The major isoprenoid quinone was ubiquinone-8 (Q-8) and the DNA G+C content of the genomic DNA was 69.6 mol%. Phylogenetic analyses, based on 16S rRNA gene sequences, showed that the novel isolate belongs to the genus Melaminivora and was most closely related to Melaminivora alkalimesophila CY1T (97.2 % similarity). The DNA-DNA relatedness values between strain KBB12T and M. alkalimesophila DSM26005T was 43.4±2.7 %. On the basis of phylogenetic and phenotypic evidence, it is proposed that strain KBB12T represents a novel species of the genus Melaminivora, for which the name Melaminivora jejuensis sp. nov. is proposed. The type strain is KBB12T (=KCTC 32230T=JCM 18740T).}, } @article {pmid29111966, year = {2018}, author = {Liu, B and Liu, GH and Wang, XY and Wang, JP and Zhu, YJ and Zhang, HF and Sengonca, C}, title = {Bacillus populi sp. nov. isolated from Populus euphratica rhizosphere soil of the Taklamakan desert.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {155-159}, doi = {10.1099/ijsem.0.002476}, pmid = {29111966}, issn = {1466-5034}, mesh = {Bacillus/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; China ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; Populus/*microbiology ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A rod-shaped, endospore-forming, aerobic bacterium, designated FJAT-45347T, was isolated from rhizosphere soil collected from the Taklamakan desert in Xinjiang (PR China). Growth was observed at 15-35 °C (optimum 25 °C), in 0 % and 20.0 % NaCl (optimum 8.0 %) and at pH 7.5-12.0 (optimum 8.0), respectively. The cell-wall peptidoglycan contained meso-diaminopimelic acid and the isoprenoid quinone was MK-7. The main fatty acids were iso-C15 : 0, anteiso-C15 : 0 and anteiso-C17 : 0. The main polar lipids were diphosphatidylglycerol, phosphatidylglycerol and phosphatidylethanolamine. Phylogenetic analysis based on 16S rRNA gene sequences affiliated FJAT-45347T to the genus Bacillus, and it showed the highest sequence similarities to Bacillus clarkii DSM 8720T (96.1 %). The average nucleotide identity and in silico DNA-DNA hybridization values between FJAT-45347T and the most closely related species were 68.5 and 26.2 %, respectively, which were lower than the thresholds commonly used to define species (96 and 70 %, respectively), indicating that it represented a member of a different taxon. The DNA G+C content was 40.6 mol%. The phenotypic characters and taxono-genomics study revealed that FJAT-45347T represents a novel species of the genus Bacillus, for which the name Bacilluspopuli sp. nov. is proposed. The type strain is FJAT-45347T (=DSM 104632T=CCTCC AB 2016257T).}, } @article {pmid29111965, year = {2018}, author = {Ekwe, AP and Kim, SB}, title = {Flavobacterium commune sp. nov., isolated from freshwater and emended description of Flavobacterium seoulense.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {93-98}, doi = {10.1099/ijsem.0.002463}, pmid = {29111965}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Flavobacterium/*classification/genetics/isolation & purification ; Fresh Water/*microbiology ; Phospholipids/chemistry ; *Phylogeny ; Pigmentation ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-negative, yellow, facultatively-anaerobic, short, rod-shaped, non-spore-forming bacterium, designated PK15T, was isolated from freshwater. Growth was observed at 4-40 °C (optimum, 30 °C), pH 6-9 (optimum, 8), and in the presence of 0-0.8 % (w/v) NaCl (optimum, 0.4 %). Strain PK15T exhibited both catalase and oxidase activities and was able to reduce nitrate. On the basis of 16S rRNA gene sequence similarities, strain PK15T was shown to belong to the genus Flavobacterium with close similarities to Flavobacterium palustre S44T (97.9 %) and Flavobacterium seoulense EM1321T (97.7 %). Menaquinone-6 (MK-6) was the major respiratory quinone, while the G+C content of the genomic DNA was 35.5 (±0.9) mol%. The major polar lipids were phosphatidylethanolamine, three unidentified aminolipids, one unidentified aminophospholipid and three unidentified polar lipids. The predominant cellular fatty acids (≥10 %) were anteiso-C15 : 0 (17.3 %), a summed feature comprising C16 : 1ω7c and/or C16 : 1ω6c (15.1 %) and iso-C15 : 0 (10.0 %). Chemotaxonomic data supported the affiliation of strain PK15T to the genus Flavobacterium. The results of physiological and biochemical tests allowed genotypic and phenotypic differentiation of strain PK15T from strains of closely related species. It was, therefore, evident that PK15T represents a novel species of the genus Flavobacterium, for which the name Flavobacterium commune sp. nov. is proposed with strain PK15T (=KCTC 52562T=JCM 32115T) as the type strain. Based on the results of the chemotaxonomic characterization in the present study, an emended description of Flavobacterium seoulense is also proposed.}, } @article {pmid29111610, year = {2018}, author = {Ruch, H and Zürcher, Y and Burkart, JM}, title = {The function and mechanism of vocal accommodation in humans and other primates.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {996-1013}, doi = {10.1111/brv.12382}, pmid = {29111610}, issn = {1469-185X}, abstract = {The study of non-human animals, in particular primates, can provide essential insights into language evolution. A critical element of language is vocal production learning, i.e. learning how to produce calls. In contrast to other lineages such as songbirds, vocal production learning of completely new signals is strikingly rare in non-human primates. An increasing body of research, however, suggests that various species of non-human primates engage in vocal accommodation and adjust the structure of their calls in response to environmental noise or conspecific vocalizations. To date it is unclear what role vocal accommodation may have played in language evolution, in particular because it summarizes a variety of heterogeneous phenomena which are potentially achieved by different mechanisms. In contrast to non-human primates, accommodation research in humans has a long tradition in psychology and linguistics. Based on theoretical models from these research traditions, we provide a new framework which allows comparing instances of accommodation across species, and studying them according to their underlying mechanism and ultimate biological function. We found that at the mechanistic level, many cases of accommodation can be explained with an automatic perception-production link, but some instances arguably require higher levels of vocal control. Functionally, both human and non-human primates use social accommodation to signal social closeness or social distance to a partner or social group. Together, this indicates that not only some vocal control, but also the communicative function of vocal accommodation to signal social closeness and distance must have evolved prior to the emergence of language, rather than being the result of it. Vocal accommodation as found in other primates has thus endowed our ancestors with pre-adaptations that may have paved the way for language evolution.}, } @article {pmid29111477, year = {2018}, author = {Streicher, JW and Miller, EC and Guerrero, PC and Correa, C and Ortiz, JC and Crawford, AJ and Pie, MR and Wiens, JJ}, title = {Evaluating methods for phylogenomic analyses, and a new phylogeny for a major frog clade (Hyloidea) based on 2214 loci.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {128-143}, doi = {10.1016/j.ympev.2017.10.013}, pmid = {29111477}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification ; Conserved Sequence/genetics ; *Genetic Loci ; Genomics/*methods ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Phylogenomic approaches offer a wealth of data, but a bewildering diversity of methodological choices. These choices can strongly affect the resulting topologies. Here, we explore two controversial approaches (binning genes into "supergenes" and inclusion of only rapidly evolving sites), using new data from hyloid frogs. Hyloid frogs encompass ∼53% of frog species, including true toads (Bufonidae), glassfrogs (Centrolenidae), poison frogs (Dendrobatidae), and treefrogs (Hylidae). Many hyloid families are well-established, but relationships among these families have remained difficult to resolve. We generated a dataset of ultraconserved elements (UCEs) for 50 ingroup species, including 18 of 19 hyloid families and up to 2214 loci spanning >800,000 aligned base pairs. We evaluated these two general approaches (binning, rapid sites only) based primarily on their ability to recover and strongly support well-established clades. Data were analyzed using concatenated likelihood and coalescent species-tree methods (NJst, ASTRAL). Binning strongly affected inferred relationships, whereas use of only rapidly evolving sites did not (indicating ∼87% of the data contributed little information). The optimal approaches for maximizing recovery and support of well-established clades were concatenated likelihood analysis and the use of a limited number of naive bins (statistical binning gave more problematic results). These two optimal approaches converged on similar relationships among hyloid families, and resolved them with generally strong support. The relationships found were very different from most previous estimates of hyloid phylogeny, and a new classification is proposed. The new phylogeny also suggests an intriguing biogeographical scenario, in which hyloids originated in southern South America before radiating throughout the world.}, } @article {pmid29111476, year = {2018}, author = {Lopes, JC and Chatrou, LW and Mello-Silva, R and Rudall, PJ and Sajo, MG}, title = {Phylogenomics and evolution of floral traits in the Neotropical tribe Malmeeae (Annonaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {379-391}, doi = {10.1016/j.ympev.2017.10.020}, pmid = {29111476}, issn = {1095-9513}, mesh = {Annonaceae/anatomy & histology/*classification/genetics ; Bayes Theorem ; Biological Evolution ; Chloroplasts/genetics ; DNA, Chloroplast/chemistry/isolation & purification/metabolism ; Flowers/anatomy & histology/genetics ; Likelihood Functions ; Microscopy, Electron, Scanning ; Phenotype ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Androdioecy is the rarest sexual system among plants. The majority of androdioecious species are herbaceous plants that have evolved from dioecious ancestors. Nevertheless, some woody and androdioecious plants have hermaphrodite ancestors, as in the Annonaceae, where androdioecious genera have arisen several times in different lineages. The majority of androdioecious species of Annonaceae belong to the Neotropical tribe Malmeeae. In addition to these species, Pseudoxandra spiritus-sancti was recently confirmed to be androdioecious. Here, we describe the morphology of male and bisexual flowers of Pseudoxandra spiritus-sancti, and investigate the evolution of androdioecy in Malmeeae. The phylogeny of tribe Malmeeae was reconstructed using Bayesian inference, maximum parsimony and maximum likelihood of 32 taxa, using DNA sequences of 66 molecular markers of the chloroplast genome, sequenced by next generation sequencing. The reconstruction of ancestral states was performed for characters associated with sexual systems and floral morphology. The phylogenetic analyses reconstructed three main groups in Malmeeae, (Malmea (Cremastosperma, Pseudoxandra)) sister to the rest of the tribe, and (Unonopsis (Bocageopsis, Onychopetalum)) sister to (Mosannona, Ephedranthus, Klarobelia, Oxandra, Pseudephedranthus fragrans, Pseudomalmea, Ruizodendron ovale). Hermaphroditism is plesiomorphic in the tribe, with four independent evolutions of androdieocy, which represents a synapomorphy of two groups, one that includes three genera and 14 species, the other with a single genus of seven species. Male flowers are unisexual from inception and bisexual flowers possess staminodes and functional stamens. Pseudoxandra spiritus-sancti is structurally androdioecious.}, } @article {pmid29111475, year = {2018}, author = {Wei, R and Ebihara, A and Zhu, YM and Zhao, CF and Hennequin, S and Zhang, XC}, title = {A total-evidence phylogeny of the lady fern genus Athyrium Roth (Athyriaceae) with a new infrageneric classification.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {25-36}, doi = {10.1016/j.ympev.2017.10.019}, pmid = {29111475}, issn = {1095-9513}, mesh = {Bayes Theorem ; Databases, Genetic ; Ferns/anatomy & histology/*classification ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The lady fern genus Athyrium represents one of the most diversified lineages in Athyriaceae with about 160-220 known species, and is notorious for its taxonomic difficulty. Despite progress in recent phylogenetic studies involving this genus, it still lacks a modern systematic and taxonomic update using integrative analyses of molecular and morphological evidence based on a broad species sampling. Here, we present, to our knowledge, the most comprehensive phylogenetic analysis of the genus to date based on a total-evidence approach, covering all formerly accepted segregates within the athyrioid ferns. We sampled up to eight plastid markers and 20 morphological characters for each species. Our analyses, including maximum parsimony, maximum likelihood and Bayesian inference, yield a robust phylogenetic framework. We find that Athyrium is not monophyletic by recovering Athyrium skinneri and A. alpestre nested with Anisocampium and Cornopteris respectively while Pseudocystopteris is included in Athyrium. Furthermore, eight well-resolved clades and two isolated species within Athyrium are found in the phylogenetic topology, which can be also characterized by morphological synapomorphies from traits of petioles, leaves, sori and spores. In the interest of recognizing monophyletic taxa with morphological synapomorphies, we agree with the inclusion of Pseudocystopteris in Athyrium as proposed in previous studies, but treat Anisocampium and Cornopteris as separate genera. We further propose to resurrect a monotypic Pseudathyrium to accommodate A. alpestre. Based on morphological characters and molecular phylogeny, a new infrageneric classification system of Athyrium is proposed which subdivided it into ten sections, and one New-World species A. skinneri is transferred into Anisocampium.}, } @article {pmid29111100, year = {2018}, author = {Johnson, K and Bateman, J and DiTommaso, T and Wong, AY and Whited, JL}, title = {Systemic cell cycle activation is induced following complex tissue injury in axolotl.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {461-472}, pmid = {29111100}, issn = {1095-564X}, support = {DP2 HD087953/HD/NICHD NIH HHS/United States ; R03 AR068126/AR/NIAMS NIH HHS/United States ; }, mesh = {Ambystoma mexicanum/injuries/*physiology ; Amputation ; Animals ; Bone Regeneration/physiology ; Cartilage/physiology ; *Cell Cycle ; Crush Injuries/physiopathology ; DNA Replication ; Dermis/physiology ; Epidermis/physiology ; Extremities/injuries/physiology ; Nerve Regeneration/physiology ; Organ Specificity ; Regeneration/*physiology ; Satellite Cells, Skeletal Muscle/physiology ; Skin/injuries ; TOR Serine-Threonine Kinases/physiology ; Wound Healing/genetics/physiology ; }, abstract = {Activation of progenitor cells is crucial to promote tissue repair following injury in adult animals. In the context of successful limb regeneration following amputation, progenitor cells residing within the stump must re-enter the cell cycle to promote regrowth of the missing limb. We demonstrate that in axolotls, amputation is sufficient to induce cell-cycle activation in both the amputated limb and the intact, uninjured contralateral limb. Activated cells were found throughout all major tissue populations of the intact contralateral limb, with internal cellular populations (bone and soft tissue) the most affected. Further, activated cells were additionally found within the heart, liver, and spinal cord, suggesting that amputation induces a common global activation signal throughout the body. Among two other injury models, limb crush and skin excisional wound, only limb crush injuries were capable of inducing cellular responses in contralateral uninjured limbs but did not achieve activation levels seen following limb loss. We found this systemic activation response to injury is independent of formation of a wound epidermis over the amputation plane, suggesting that injury-induced signals alone can promote cellular activation. In mammals, mTOR signaling has been shown to promote activation of quiescent cells following injury, and we confirmed a subset of activated contralateral cells is positive for mTOR signaling within axolotl limbs. These findings suggest that conservation of an early systemic response to injury exists between mammals and axolotls, and propose that a distinguishing feature in species capable of full regeneration is converting this initial activation into sustained and productive growth at the site of regeneration.}, } @article {pmid29109555, year = {2018}, author = {Bell, LCK and Noursadeghi, M}, title = {Pathogenesis of HIV-1 and Mycobacterium tuberculosis co-infection.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {80-90}, pmid = {29109555}, issn = {1740-1534}, abstract = {Co-infection with Mycobacterium tuberculosis is the leading cause of death in individuals infected with HIV-1. It has long been known that HIV-1 infection alters the course of M. tuberculosis infection and substantially increases the risk of active tuberculosis (TB). It has also become clear that TB increases levels of HIV-1 replication, propagation and genetic diversity. Therefore, co-infection provides reciprocal advantages to both pathogens. In this Review, we describe the epidemiological associations between the two pathogens, selected interactions of each pathogen with the host and our current understanding of how they affect the pathogenesis of TB and HIV-1/AIDS in individuals with co-infections. We evaluate the mechanisms and consequences of HIV-1 depletion of T cells on immune responses to M. tuberculosis. We also discuss the effect of HIV-1 infection on the control of M. tuberculosis by macrophages through phagocytosis, autophagy and cell death, and we propose models by which dysregulated inflammatory responses drive the pathogenesis of TB and HIV-1/AIDS.}, } @article {pmid29109554, year = {2018}, author = {Petrova, VN and Russell, CA}, title = {The evolution of seasonal influenza viruses.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {60}, doi = {10.1038/nrmicro.2017.146}, pmid = {29109554}, issn = {1740-1534}, abstract = {This corrects the article DOI: 10.1038/nrmicro.2017.118.}, } @article {pmid29109524, year = {2018}, author = {Nelson, R and Wiesner-Hanks, T and Wisser, R and Balint-Kurti, P}, title = {Navigating complexity to breed disease-resistant crops.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {21-33}, pmid = {29109524}, issn = {1471-0064}, mesh = {Crops, Agricultural/*genetics ; Genes, Plant ; Genetic Pleiotropy ; Genetic Predisposition to Disease ; Genetic Variation ; Host-Pathogen Interactions/genetics ; Plant Breeding/*methods ; Plant Diseases/*genetics/*prevention & control ; }, abstract = {Plant diseases are responsible for substantial crop losses each year and pose a threat to global food security and agricultural sustainability. Improving crop resistance to pathogens through breeding is an environmentally sound method for managing disease and minimizing these losses. However, it is challenging to breed varieties with resistance that is effective, stable and broad-spectrum. Recent advances in genetic and genomic technologies have contributed to a better understanding of the complexity of host-pathogen interactions and have identified some of the genes and mechanisms that underlie resistance. This new knowledge is benefiting crop improvement through better-informed breeding strategies that utilize diverse forms of resistance at different scales, from the genome of a single plant to the plant varieties deployed across a region.}, } @article {pmid29109479, year = {2018}, author = {Tan, B and Liu, H and Zhang, S and da Silva, SR and Zhang, L and Meng, J and Cui, X and Yuan, H and Sorel, O and Zhang, SW and Huang, Y and Gao, SJ}, title = {Viral and cellular N6-methyladenosine and N6,2'-O-dimethyladenosine epitranscriptomes in the KSHV life cycle.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {108-120}, pmid = {29109479}, issn = {2058-5276}, support = {R01 CA197153/CA/NCI NIH HHS/United States ; R01 CA096512/CA/NCI NIH HHS/United States ; R01 CA124332/CA/NCI NIH HHS/United States ; R01 CA213275/CA/NCI NIH HHS/United States ; R01 DE025465/DE/NIDCR NIH HHS/United States ; R01 CA177377/CA/NCI NIH HHS/United States ; R01 GM113245/GM/NIGMS NIH HHS/United States ; R01 CA132637/CA/NCI NIH HHS/United States ; }, mesh = {Adenosine/*analogs & derivatives/metabolism ; Animals ; Cell Line ; Gene Expression Profiling ; Gene Expression Regulation, Viral ; Herpesviridae Infections/*genetics/metabolism/virology ; Herpesvirus 8, Human/*genetics/growth & development/metabolism ; Humans ; Life Cycle Stages ; RNA Processing, Post-Transcriptional ; RNA, Messenger/*metabolism ; *Transcriptome ; Viral Proteins/genetics/metabolism ; Virus Activation ; Virus Latency ; Virus Replication ; }, abstract = {N6-methyladenosine (m6A) and N6,2'-O-dimethyladenosine (m6Am) modifications (m6A/m) of messenger RNA mediate diverse cellular functions. Oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV) has latent and lytic replication phases that are essential for the development of KSHV-associated cancers. To date, the role of m6A/m in KSHV replication and tumorigenesis is unclear. Here, we provide mechanistic insights by examining the viral and cellular m6A/m epitranscriptomes during KSHV latent and lytic infection. KSHV transcripts contain abundant m6A/m modifications during latent and lytic replication, and these modifications are highly conserved among different cell types and infection systems. Knockdown of YTHDF2 enhanced lytic replication by impeding KSHV RNA degradation. YTHDF2 binds to viral transcripts and differentially mediates their stability. KSHV latent infection induces 5' untranslated region (UTR) hypomethylation and 3'UTR hypermethylation of the cellular epitranscriptome, regulating oncogenic and epithelial-mesenchymal transition pathways. KSHV lytic replication induces dynamic reprogramming of epitranscriptome, regulating pathways that control lytic replication. These results reveal a critical role of m6A/m modifications in KSHV lifecycle and provide rich resources for future investigations.}, } @article {pmid29109478, year = {2018}, author = {Kolinko, S and Wu, YW and Tachea, F and Denzel, E and Hiras, J and Gabriel, R and Bäcker, N and Chan, LJG and Eichorst, SA and Frey, D and Chen, Q and Azadi, P and Adams, PD and Pray, TR and Tanjore, D and Petzold, CJ and Gladden, JM and Simmons, BA and Singer, SW}, title = {A bacterial pioneer produces cellulase complexes that persist through community succession.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {99-107}, doi = {10.1038/s41564-017-0052-z}, pmid = {29109478}, issn = {2058-5276}, support = {S10 OD018530/OD/NIH HHS/United States ; }, mesh = {Bacteria/*classification/*enzymology/metabolism ; Bacterial Proteins/analysis/isolation & purification ; Biological Evolution ; Cellulase/*analysis/isolation & purification ; Cellulose/*metabolism ; Composting ; Genome, Bacterial/genetics ; Glycoside Hydrolases/analysis/isolation & purification ; Glycosylation ; Heterotrophic Processes ; Metagenomics ; Microbial Consortia/*physiology ; Models, Biological ; Multienzyme Complexes/*analysis/isolation & purification ; *Phylogeny ; Soil Microbiology ; }, abstract = {Cultivation of microbial consortia provides low-complexity communities that can serve as tractable models to understand community dynamics. Time-resolved metagenomics demonstrated that an aerobic cellulolytic consortium cultivated from compost exhibited community dynamics consistent with the definition of an endogenous heterotrophic succession. The genome of the proposed pioneer population, 'Candidatus Reconcilibacillus cellulovorans', possessed a gene cluster containing multidomain glycoside hydrolases (GHs). Purification of the soluble cellulase activity from a 300litre cultivation of this consortium revealed that ~70% of the activity arose from the 'Ca. Reconcilibacillus cellulovorans' multidomain GHs assembled into cellulase complexes through glycosylation. These remarkably stable complexes have supramolecular structures for enzymatic cellulose hydrolysis that are distinct from cellulosomes. The persistence of these complexes during cultivation indicates that they may be active through multiple cultivations of this consortium and act as public goods that sustain the community. The provision of extracellular GHs as public goods may influence microbial community dynamics in native biomass-deconstructing communities relevant to agriculture, human health and biotechnology.}, } @article {pmid29109477, year = {2018}, author = {Real, E and Rodrigues, L and Cabal, GG and Enguita, FJ and Mancio-Silva, L and Mello-Vieira, J and Beatty, W and Vera, IM and Zuzarte-Luís, V and Figueira, TN and Mair, GR and Mota, MM}, title = {Plasmodium UIS3 sequesters host LC3 to avoid elimination by autophagy in hepatocytes.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {17-25}, pmid = {29109477}, issn = {2058-5276}, support = {311502//European Research Council/International ; }, mesh = {Animals ; Autophagosomes/metabolism ; Autophagy/*physiology ; Cell Line ; HEK293 Cells ; Hep G2 Cells ; Hepatocytes/parasitology/*pathology/ultrastructure ; Host-Pathogen Interactions ; Humans ; Malaria/*parasitology/*pathology/physiopathology ; Male ; Membrane Proteins/genetics/*metabolism ; Mice ; Mice, Inbred C57BL ; Microtubule-Associated Proteins/*metabolism ; Models, Molecular ; Plasmodium berghei/*genetics/metabolism/pathogenicity ; Protein Binding ; Protozoan Proteins/genetics/metabolism ; Vacuoles/metabolism ; }, abstract = {The causative agent of malaria, Plasmodium, replicates inside a membrane-bound parasitophorous vacuole (PV), which shields this intracellular parasite from the cytosol of the host cell 1 . One common threat for intracellular pathogens is the homeostatic process of autophagy, through which cells capture unwanted intracellular material for lysosomal degradation 2 . During the liver stage of a malaria infection, Plasmodium parasites are targeted by the autophagy machinery of the host cell, and the PV membrane (PVM) becomes decorated with several autophagy markers, including LC3 (microtubule-associated protein 1 light chain 3) 3,4 . Here we show that Plasmodium berghei parasites infecting hepatic cells rely on the PVM transmembrane protein UIS3 to avoid elimination by host-cell-mediated autophagy. We found that UIS3 binds host LC3 through a non-canonical interaction with a specialized surface on LC3 where host proteins with essential functions during autophagy also bind. UIS3 acts as a bona fide autophagy inhibitor by competing with host LC3-interacting proteins for LC3 binding. Our work identifies UIS3, one of the most promising candidates for a genetically attenuated vaccine against malaria 5 , as a unique and potent mediator of autophagy evasion in Plasmodium. We propose that the protein-protein interaction between UIS3 and host LC3 represents a target for antimalarial drug development.}, } @article {pmid29108937, year = {2018}, author = {Copilaş-Ciocianu, D and Fišer, C and Borza, P and Petrusek, A}, title = {Is subterranean lifestyle reversible? Independent and recent large-scale dispersal into surface waters by two species of the groundwater amphipod genus Niphargus.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {37-49}, doi = {10.1016/j.ympev.2017.10.023}, pmid = {29108937}, issn = {1095-9513}, mesh = {Amphipoda/genetics/*physiology ; Animal Migration/*physiology ; Animals ; Bayes Theorem ; Biological Evolution ; Cluster Analysis ; *Groundwater ; Haplotypes/genetics ; Phenotype ; Phylogeny ; Phylogeography ; Polymorphism, Genetic ; Species Specificity ; }, abstract = {Groundwater is an extreme environment due to its absence of light, resource scarcity and highly fragmentary nature. Successful groundwater colonizers underwent major evolutionary changes and exhibit eye and pigment loss (troglomorphies). Consequently, their chances of dispersal and survival in the well-connected surface waters are greatly decreased, resulting in significant endemism. The West Palaearctic subterranean amphipod genus Niphargus comprises hundreds of narrowly endemic and troglomorphic species. Nevertheless, a few are known to occur in surface waters, two of which, N. hrabei and N. valachicus, have extremely large ranges that even exceed those of many surface-water amphipods. We tested if this pattern results from a secondary colonization of the relatively well-connected epigean environment, and whether this ecological shift promoted the large-scale dispersal of these species. Results showed that despite their ecological and zoogeographic similarities, N. hrabei and N. valachicus are not closely related and independently colonized surface waters. Their phylogeographic patterns indicate Middle to Late Pleistocene dispersal episodes throughout the Danube lowlands, and relatively modest yet significant genetic differentiation among populations. Clustering based on morphology revealed that the two species are phenotypically closer to each other than they are to most other epigean congeners. We presume that the ecological shift to surface environments was facilitated by their ability to thrive in hypoxic waters where rheophilic competitors from the family Gammaridae cannot survive. In conclusion, our results indicate that adaptation to groundwater is not a one-way evolutionary path and that troglomorphic species can occasionally recolonize and widely disperse in surface waters.}, } @article {pmid29108936, year = {2018}, author = {Deanna, R and Barboza, GE and Carrizo García, C}, title = {Phylogenetic relationships of Deprea: New insights into the evolutionary history of physaloid groups.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {71-80}, doi = {10.1016/j.ympev.2017.11.001}, pmid = {29108936}, issn = {1095-9513}, mesh = {Base Sequence ; Bayes Theorem ; Chloroplasts/genetics ; DNA, Plant/genetics ; Genetic Markers ; Geography ; *Phylogeny ; Sequence Analysis, DNA ; Solanaceae/*classification/genetics ; South America ; }, abstract = {Deprea is the genus with the second highest species richness in tribe Physalideae (Solanaceae) and comprises 50 species that are mainly distributed in the Andes of South America. The taxonomy of Deprea has been unstable after controversial hypotheses about its position and circumscription. Additionally, biogeographical inferences are only based on observations of the restricted area of distribution of some species and no ancestral area estimation have been performed. Here, we present a phylogenetic analysis and an ancestral area reconstruction of Deprea in order to establish its circumscription, resolve its position within Physalideae, and reconstruct its biogeographical history. Phylogenetic analyses were conducted using Maximum Likelihood and Bayesian approaches. Forty-three Deprea species and 26 related taxa were sampled for three DNA markers (psbA-trnH, ITS, and waxy). A Bayesian binary MCMC model was applied in order to infer ancestral areas. Deprea is resolved as a strongly supported monophyletic group according to its current circumscription and is placed within subtribe Withaninae of Physalideae. The phylogenetic relationships enabled us to solve taxonomic problems including the rejection and acceptance of previous synonyms. The most probable ancestral area for Deprea is the Northern Andes of South America and the Amotape-Huancabamba zone. Our phylogeny provides increased resolution and support for the current position and circumscription of Deprea. Better resolution of interspecific relationships was also obtained, although some affinities remain unclear. The phylogenetic and ancestral area reconstructions provide a framework for addressing taxonomic problems and investigating new evolutionary questions.}, } @article {pmid29108781, year = {2018}, author = {Uribe, RA and Hong, SS and Bronner, ME}, title = {Retinoic acid temporally orchestrates colonization of the gut by vagal neural crest cells.}, journal = {Developmental biology}, volume = {433}, number = {1}, pages = {17-32}, pmid = {29108781}, issn = {1095-564X}, support = {F32 HD080343/HD/NICHD NIH HHS/United States ; L40 HD085258/HD/NICHD NIH HHS/United States ; }, mesh = {Animals ; Cell Differentiation/physiology ; Cell Movement ; Digestive System ; Digestive System Physiological Phenomena ; Enteric Nervous System/metabolism ; Neural Crest/*metabolism/physiology ; Neuroglia/metabolism ; Neurons/metabolism ; Organogenesis/physiology ; Tretinoin/*metabolism/physiology ; Zebrafish/embryology/metabolism ; }, abstract = {The enteric nervous system arises from neural crest cells that migrate as chains into and along the primitive gut, subsequently differentiating into enteric neurons and glia. Little is known about the mechanisms governing neural crest migration en route to and along the gut in vivo. Here, we report that Retinoic Acid (RA) temporally controls zebrafish enteric neural crest cell chain migration. In vivo imaging reveals that RA loss severely compromises the integrity and migration of the chain of neural crest cells during the window of time window when they are moving along the foregut. After loss of RA, enteric progenitors accumulate in the foregut and differentiate into enteric neurons, but subsequently undergo apoptosis resulting in a striking neuronal deficit. Moreover, ectopic expression of the transcription factor meis3 and/or the receptor ret, partially rescues enteric neuron colonization after RA attenuation. Collectively, our findings suggest that retinoic acid plays a critical temporal role in promoting enteric neural crest chain migration and neuronal survival upstream of Meis3 and RET in vivo.}, } @article {pmid29108673, year = {2018}, author = {Gufler, S and Artes, B and Bielen, H and Krainer, I and Eder, MK and Falschlunger, J and Bollmann, A and Ostermann, T and Valovka, T and Hartl, M and Bister, K and Technau, U and Hobmayer, B}, title = {β-Catenin acts in a position-independent regeneration response in the simple eumetazoan Hydra.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {310-323}, doi = {10.1016/j.ydbio.2017.09.005}, pmid = {29108673}, issn = {1095-564X}, mesh = {Animals ; Body Patterning ; Fetal Proteins/physiology ; Gene Expression Regulation ; Hydra/*physiology ; In Situ Hybridization ; Organ Specificity ; Protein Biosynthesis ; Regeneration/drug effects/*physiology ; T-Box Domain Proteins/physiology ; *Wnt Signaling Pathway ; beta Catenin/antagonists & inhibitors/genetics/*physiology ; }, abstract = {Wnt/β-Catenin signaling plays crucial roles in regenerative processes in eumetazoans. It also acts in regeneration and axial patterning in the simple freshwater polyp Hydra, whose morphallactic regenerative capacity is unparalleled in the animal kingdom. Previous studies have identified β-catenin as an early response gene activated within the first 30min in Hydra head regeneration. Here, we have studied the role of β-Catenin in more detail. First, we show that nuclear β-Catenin signaling is required for head and foot regeneration. Loss of nuclear β-Catenin function blocks head and foot regeneration. Transgenic Hydra tissue, in which β-Catenin is over-expressed, regenerates more heads and feet. In addition, we have identified a set of putative β-Catenin target genes by transcriptional profiling, and these genes exhibit distinct expression patterns in the hypostome, in the tentacles, or in an apical gradient in the body column. All of them are transcriptionally up-regulated in the tips of early head and foot regenerates. In foot regenerates, this is a transient response, and expression starts to disappear after 12-36h. ChIP experiments using an anti-HydraTcf antibody show Tcf binding at promoters of these targets. We propose that gene regulatory β-Catenin activity in the pre-patterning phase is generally required as an early regeneration response. When regenerates are blocked with iCRT14, initial local transcriptional activation of β-catenin and the target genes occurs, and all these genes remain upregulated at the site of both head and foot regeneration for the following 2-3 days. This indicates that the initial regulatory network is followed by position-specific programs that inactivate fractions of this network in order to proceed to differentiation of head or foot structures. brachyury1 (hybra1) has previously been described as early response gene in head and foot regeneration. The HyBra1 protein, however, appears in head regenerating tips not earlier than about twelve hours after decapitation, and HyBra1 translation does not occur in iCRT14-treated regenerates. Foot regenerates never show detectable levels of HyBra1 protein at all. These results suggest that translational control mechanisms may play a decisive role in the head- and foot-specific differentiation phase, and HyBra1 is an excellent candidate for such a key regulator of head specification.}, } @article {pmid29108672, year = {2018}, author = {Lan, Q and Cao, M and Kollipara, RK and Rosa, JB and Kittler, R and Jiang, H}, title = {FoxA transcription factor Fork head maintains the intestinal stem/progenitor cell identities in Drosophila.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {324-343}, doi = {10.1016/j.ydbio.2017.09.002}, pmid = {29108672}, issn = {1095-564X}, support = {R01 DK102576/DK/NIDDK NIH HHS/United States ; }, mesh = {Animals ; Basic Helix-Loop-Helix Transcription Factors/physiology ; Binding Sites ; Cell Lineage ; Cell Self Renewal ; Chromatin/metabolism ; Cytokines/metabolism ; Drosophila Proteins/physiology ; Drosophila melanogaster/cytology/genetics/*physiology ; Enterocytes/metabolism ; Forkhead Transcription Factors/*physiology ; Gene Expression Regulation ; Intestines/*cytology ; Nuclear Proteins/*physiology ; RNA Interference ; Stem Cells/*physiology ; Transcription Factors/physiology ; }, abstract = {Understanding how somatic stem cells respond to tissue needs is important, since aberrant somatic stem cell behaviors may lead to tissue degeneration or tumorigenesis. Here, from an in vivo RNAi screen targeting transcription factors that regulate intestinal regeneration, we uncovered a requirement for the Drosophila FoxA transcription factor Fork head (Fkh) in the maintenance of intestinal stem/progenitor cell identities. FoxA/Fkh maintains the expressions of stem/progenitor cell markers and is required for stem cell proliferation during intestinal homeostasis and regeneration. Furthermore, FoxA/Fkh prevents the intestinal stem/progenitor cells from precocious differentiation into the Enterocyte lineage, likely in cooperation with the transcription factor bHLH/Daughterless (Da). In addition, loss of FoxA/Fkh suppresses the intestinal tumorigenesis caused by Notch pathway inactivation. To reveal the gene program underlying stem/progenitor cell identities, we profiled the genome-wide chromatin binding sites of transcription factors Fkh and Da, and interestingly, around half of Fkh binding regions are shared by Da, further suggesting their collaborative roles. Finally, we identified the genes associated with their shared binding regions. This comprehensive gene list may contain stem/progenitor maintenance factors functioning downstream of Fkh and Da, and would be helpful for future gene discoveries in the Drosophila intestinal stem cell lineage.}, } @article {pmid29107897, year = {2018}, author = {Golding, I}, title = {Infection by bacteriophage lambda: an evolving paradigm for cellular individuality.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {9-13}, pmid = {29107897}, issn = {1879-0364}, support = {R01 GM082837/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteriophage lambda/genetics/*physiology ; Escherichia coli/*virology ; Humans ; Molecular Biology/methods ; Single-Cell Analysis ; }, abstract = {Since the earliest days of molecular biology, bacteriophage lambda has served to illuminate cellular function. Among its many roles, lambda infection is a paradigm for phenotypic heterogeneity among genetically identical cells. Early studies attributed this cellular individuality to random biochemical fluctuations, or 'noise'. More recently, however, attention has turned to the role played by deterministic hidden variables in driving single-cell behavior. Here, I briefly describe how studies in lambda are driving the shift in our understanding of cellular heterogeneity, allowing us to better appreciate the precision at which cells function.}, } @article {pmid29107896, year = {2018}, author = {Cassidy, CK and Himes, BA and Luthey-Schulten, Z and Zhang, P}, title = {CryoEM-based hybrid modeling approaches for structure determination.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {14-23}, pmid = {29107896}, issn = {1879-0364}, support = {//Wellcome Trust/United Kingdom ; P41 GM104601/GM/NIGMS NIH HHS/United States ; R01 GM085043/GM/NIGMS NIH HHS/United States ; 206422/Z/17/Z//Wellcome Trust/United Kingdom ; }, mesh = {Computational Biology ; Computer Simulation ; Cryoelectron Microscopy/*methods ; *Models, Molecular ; Protein Conformation ; }, abstract = {Recent advances in cryo-electron microscopy (cryoEM) have dramatically improved the resolutions at which vitrified biological specimens can be studied, revealing new structural and mechanistic insights over a broad range of spatial scales. Bolstered by these advances, much effort has been directed toward the development of hybrid modeling methodologies for the construction and refinement of high-fidelity atomistic models from cryoEM data. In this brief review, we will survey the key elements of cryoEM-based hybrid modeling, providing an overview of available computational tools and strategies as well as several recent applications.}, } @article {pmid29107619, year = {2018}, author = {Chueca, LJ and Gómez-Moliner, BJ and Madeira, MJ and Pfenninger, M}, title = {Molecular phylogeny of Candidula (Geomitridae) land snails inferred from mitochondrial and nuclear markers reveals the polyphyly of the genus.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {357-368}, doi = {10.1016/j.ympev.2017.10.022}, pmid = {29107619}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Cell Nucleus/*genetics ; Electron Transport Complex IV/chemistry/genetics ; Evolution, Molecular ; Mitochondria/*genetics ; Phylogeny ; RNA, Ribosomal, 16S/chemistry/genetics ; RNA, Ribosomal, 28S/chemistry/genetics ; RNA, Ribosomal, 5.8S/chemistry/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; Snails/*classification/genetics ; }, abstract = {The genus Candidula (Geomitridae), consisting of 28 species in Western Europe as currently described, has a disjunct distribution in the Iberian Peninsula, Italy, the Balkans, the Aegean Islands, and one species on the Canary Islands. Although the genus is seemingly well defined by characters of the reproductive system, the relationships within the genus are still unclear and some authors have indicated a possible subgeneric division based on the internal morphology of the dart sac. Despite substantial phylogenetic incongruence, we present a well-resolved molecular phylogeny of Candidula based on two mitochondrial genes (COI and 16S rRNA), the nuclear rDNA region (5.8S rNRA + ITS2 + 28S rRNA) and seven additional nuclear DNA regions developed specifically for this genus (60SL13, 60SL17, 60SL7, RPL14, 40SS6, 60SL9, 60SL13a), in total 5595 bp. Six reciprocally monophyletic entities including Candidula species were recovered, grouping into two major clades. The incorporation of additional geomitrid genera allowed us to unequivocally demonstrate the polyphyly of the genus Candidula. One major clade grouped species from southern France and Italy with the widely distributed species C. unifasciata. The second major clade grouped all the species from the Iberian Peninsula, including C. intersecta and C. gigaxii. Candidula ultima from the Canary Islands was recovered as separated lineage within the latter clade and related to African taxa. The six monophyla were defined as six new genera belonging to different tribes within the Helicellinae. Thus, we could show that similar structures of the stimulatory apparatus of the genital system in different taxa do not necessarily indicate a close phylogenetic relationship in the Geomitridae. More genera of the family are needed to clarify their evolutionary relationships, and to fully understand the evolution of the stimulatory apparatus of the genital system within the Geomitridae.}, } @article {pmid29107618, year = {2018}, author = {da Cruz, MOR and Weksler, M}, title = {Impact of tree priors in species delimitation and phylogenetics of the genus Oligoryzomys (Rodentia: Cricetidae).}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {1-12}, doi = {10.1016/j.ympev.2017.10.021}, pmid = {29107618}, issn = {1095-9513}, mesh = {Animals ; Arvicolinae/*classification ; Bayes Theorem ; Mitochondria/metabolism ; *Phylogeny ; Probability ; Species Specificity ; Time Factors ; }, abstract = {The use of genetic data and tree-based algorithms to delimit evolutionary lineages is becoming an important practice in taxonomic identification, especially in morphologically cryptic groups. The effects of different phylogenetic and/or coalescent models in the analyses of species delimitation, however, are not clear. In this paper, we assess the impact of different evolutionary priors in phylogenetic estimation, species delimitation, and molecular dating of the genus Oligoryzomys (Mammalia: Rodentia), a group with complex taxonomy and morphological cryptic species. Phylogenetic and coalescent analyses included 20 of the 24 recognized species of the genus, comprising of 416 Cytochrome b sequences, 26 Cytochrome c oxidase I sequences, and 27 Beta-Fibrinogen Intron 7 sequences. For species delimitation, we employed the General Mixed Yule Coalescent (GMYC) and Bayesian Poisson tree processes (bPTP) analyses, and contrasted 4 genealogical and phylogenetic models: Pure-birth (Yule), Constant Population Size Coalescent, Multiple Species Coalescent, and a mixed Yule-Coalescent model. GMYC analyses of trees from different genealogical models resulted in similar species delimitation and phylogenetic relationships, with incongruence restricted to areas of poor nodal support. bPTP results, however, significantly differed from GMYC for 5 taxa. Oligoryzomys early diversification was estimated to have occurred in the Early Pleistocene, between 0.7 and 2.6 MYA. The mixed Yule-Coalescent model, however, recovered younger dating estimates for Oligoryzomys diversification, and for the threshold for the speciation-coalescent horizon in GMYC. Eight of the 20 included Oligoryzomys species were identified as having two or more independent evolutionary units, indicating that current taxonomy of Oligoryzomys is still unsettled.}, } @article {pmid29107345, year = {2018}, author = {Luca, F and Kupfer, SS and Knights, D and Khoruts, A and Blekhman, R}, title = {Functional Genomics of Host-Microbiome Interactions in Humans.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {30-40}, pmid = {29107345}, issn = {0168-9525}, support = {P30 CA022453/CA/NCI NIH HHS/United States ; R01 GM109215/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Gene Expression Regulation ; *Genetic Variation ; Genome-Wide Association Study ; Genomics/methods ; Humans ; Microbiota/*genetics ; Translational Medical Research ; }, abstract = {The human microbiome has been linked to various host phenotypes and has been implicated in many complex human diseases. Recent genome-wide association studies (GWASs) have used microbiome variation as a complex trait and have uncovered human genetic variants that are associated with the microbiome. Here we summarize results from these studies and illustrate potential regulatory mechanisms by which host genetic variation can interact with microbiome composition. We argue that, similar to human GWASs, it is important to use functional genomics techniques to gain a mechanistic understanding of causal host-microbiome interactions and their role in human disease. We highlight experimental, functional, and computational genomics methodologies for the study of the genomic basis of host-microbiome interactions and describe how these approaches can be utilized to explain how human genetic variation can modulate the effects of the microbiome on the host.}, } @article {pmid29107154, year = {2018}, author = {Liu, P and Xu, L and Xu, SL and Martínez, A and Chen, H and Cheng, D and Dumont, HJ and Han, BP and Fontaneto, D}, title = {Species and hybrids in the genus Diaphanosoma Fischer, 1850 (Crustacea: Branchiopoda: Cladocera).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {369-378}, doi = {10.1016/j.ympev.2017.10.016}, pmid = {29107154}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Biological Evolution ; Cladocera/*classification/genetics ; DNA/chemistry/isolation & purification/metabolism ; DNA, Mitochondrial/genetics ; Electron Transport Complex IV/chemistry/classification/genetics ; Gene Flow ; Genetic Variation ; Hybridization, Genetic ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Cladocerans are well-studied planktonic crustaceans, especially those of the genus Daphnia in which interesting evolutionary questions have been addressed on speciation processes. The aim of the present study is to demonstrate that other genera of cladocerans show similar levels of cryptic diversity, intraspecific gene flow, and thus become useful model systems for comparison. In order to do so, we chose the genus Diaphanosoma, widespread in tropical and temperate areas. We started with a survey of species diversity in the genus Diaphanosoma in Asia using a morphological approach, then obtained sequences from a mitochondrial and a nuclear marker from multiple individuals of different species, performed tests on DNA taxonomy and molecular phylogenies, and assessed the role of hybridization in explaining the cases of mitonuclear discordance. The results are that cryptic diversity occurs in Diaphanosoma, and mitonuclear discordance was found in about 6% of the sequenced animals. Past hybridization is supported as the most likely explanation for the discordance: no evidence was found of first generation hybrids with heterozygous sequences. Our analysis on patterns of genetic diversity in Diaphanosoma supports similarities and differences with what is known in Daphnia.}, } @article {pmid29106597, year = {2018}, author = {Venev, SV and Zeldovich, KB}, title = {Thermophilic Adaptation in Prokaryotes Is Constrained by Metabolic Costs of Proteostasis.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {211-224}, pmid = {29106597}, issn = {1537-1719}, support = {P01 GM109767/GM/NIGMS NIH HHS/United States ; }, abstract = {Prokaryotes evolved to thrive in an extremely diverse set of habitats, and their proteomes bear signatures of environmental conditions. Although correlations between amino acid usage and environmental temperature are well-documented, understanding of the mechanisms of thermal adaptation remains incomplete. Here, we couple the energetic costs of protein folding and protein homeostasis to build a microscopic model explaining both the overall amino acid composition and its temperature trends. Low biosynthesis costs lead to low diversity of physical interactions between amino acid residues, which in turn makes proteins less stable and drives up chaperone activity to maintain appropriate levels of folded, functional proteins. Assuming that the cost of chaperone activity is proportional to the fraction of unfolded client proteins, we simulated thermal adaptation of model proteins subject to minimization of the total cost of amino acid synthesis and chaperone activity. For the first time, we predicted both the proteome-average amino acid abundances and their temperature trends simultaneously, and found strong correlations between model predictions and 402 genomes of bacteria and archaea. The energetic constraint on protein evolution is more apparent in highly expressed proteins, selected by codon adaptation index. We found that in bacteria, highly expressed proteins are similar in composition to thermophilic ones, whereas in archaea no correlation between predicted expression level and thermostability was observed. At the same time, thermal adaptations of highly expressed proteins in bacteria and archaea are nearly identical, suggesting that universal energetic constraints prevail over the phylogenetic differences between these domains of life.}, } @article {pmid29106350, year = {2018}, author = {Dunlap, CA and Rooney, AP}, title = {Acinetobacter dijkshoorniae is a later heterotypic synonym of Acinetobacter lactucae.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {131-132}, doi = {10.1099/ijsem.0.002470}, pmid = {29106350}, issn = {1466-5034}, mesh = {Acinetobacter/*classification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Nucleic Acid Hybridization ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {Acinetobacter lactucae and Acinetobacter dijkshoorniae were recently described as novel species, and both were reported to be closely related to Acinetobacter pittii. Because they were reviewed and published almost concurrently, their descriptions did not include a specific comparison between these two novel species. Genomic data were provided in both initial descriptions, which simplifies the comparisons. Genome comparisons based on in silico DNA-DNA hybridizations, average nucleotide identity and core genome phylogeny of the type strain genomes establish that these strains are conspecific. Based on the rules of priority, A. dijkshoorniae should be reclassified as a later heterotypic synonym of A. lactucae.}, } @article {pmid29105292, year = {2018}, author = {Dunn, FS and Liu, AG and Donoghue, PCJ}, title = {Ediacaran developmental biology.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {914-932}, pmid = {29105292}, issn = {1469-185X}, support = {BB/N000919/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {Rocks of the Ediacaran System (635-541 Ma) preserve fossil evidence of some of the earliest complex macroscopic organisms, many of which have been interpreted as animals. However, the unusual morphologies of some of these organisms have made it difficult to resolve their biological relationships to modern metazoan groups. Alternative competing phylogenetic interpretations have been proposed for Ediacaran taxa, including algae, fungi, lichens, rhizoid protists, and even an extinct higher-order group (Vendobionta). If a metazoan affinity can be demonstrated for these organisms, as advocated by many researchers, they could prove informative in debates concerning the evolution of the metazoan body axis, the making and breaking of axial symmetries, and the appearance of a metameric body plan. Attempts to decipher members of the enigmatic Ediacaran macrobiota have largely involved study of morphology: comparative analysis of their developmental phases has received little attention. Here we present what is known of ontogeny across the three iconic Ediacaran taxa Charnia masoni, Dickinsonia costata and Pteridinium simplex, together with new ontogenetic data and insights. We use these data and interpretations to re-evaluate the phylogenetic position of the broader Ediacaran morphogroups to which these taxa are considered to belong (rangeomorphs, dickinsoniomorphs and erniettomorphs). We conclude, based on the available evidence, that the affinities of the rangeomorphs and the dickinsoniomorphs lie within Metazoa.}, } @article {pmid29105274, year = {2018}, author = {Barton, IS and Fuqua, C and Platt, TG}, title = {Ecological and evolutionary dynamics of a model facultative pathogen: Agrobacterium and crown gall disease of plants.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {16-29}, pmid = {29105274}, issn = {1462-2920}, support = {R01 GM092660/GM/NIGMS NIH HHS/United States ; }, abstract = {Many important pathogens maintain significant populations in highly disparate disease and non-disease environments. The consequences of this environmental heterogeneity in shaping the ecological and evolutionary dynamics of these facultative pathogens are incompletely understood. Agrobacterium tumefaciens, the causative agent for crown gall disease of plants has proven a productive model for many aspects of interactions between pathogens and their hosts and with other microbes. In this review, we highlight how this past work provides valuable context for the use of this system to examine how heterogeneity and transitions between disease and non-disease environments influence the ecology and evolution of facultative pathogens. We focus on several features common among facultative pathogens, such as the physiological remodelling required to colonize hosts from environmental reservoirs and the consequences of competition with host and non-host associated microbiota. In addition, we discuss how the life history of facultative pathogens likely often results in ecological tradeoffs associated with performance in disease and non-disease environments. These pathogens may therefore have different competitive dynamics in disease and non-disease environments and are subject to shifting selective pressures that can result in pathoadaptation or the within-host spread of avirulent phenotypes.}, } @article {pmid29104141, year = {2018}, author = {Lüddecke, T and Krehenwinkel, H and Canning, G and Glaw, F and Longhorn, SJ and Tänzler, R and Wendt, I and Vences, M}, title = {Discovering the silk road: Nuclear and mitochondrial sequence data resolve the phylogenetic relationships among theraphosid spider subfamilies.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {63-70}, doi = {10.1016/j.ympev.2017.10.015}, pmid = {29104141}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Cell Nucleus/*genetics ; DNA, Mitochondrial/*genetics ; Mitochondria/genetics ; *Phylogeny ; Sequence Analysis, DNA ; Silk/*genetics ; Spiders/*classification/*genetics ; }, abstract = {The mygalomorph spiders in the family Theraphosidae, also known as "tarantulas", are one of the most popular and diverse groups of arachnids, but their evolutionary history remains poorly understood because morphological analyses have only provided mostly controversial results, and a broad molecular perspective has been lacking until now. In this study we provide a preliminary molecular phylogenetic hypothesis of relationships among theraphosid subfamilies, based on 3.5 kbp of three nuclear and three mitochondrial markers, for 52 taxa representing 10 of the 11 commonly accepted subfamilies. Our analysis confirms the monophyly of the Theraphosidae and of most recognized theraphosid subfamilies, supports the validity of the Stromatopelminae and Poecilotheriinae, and indicates paraphyly of the Schismatothelinae. The placement of representatives of Schismatothelinae also indicates possible non-monophyly of Aviculariinae and supports the distinction of the previously contentious subfamily Psalmopoeinae. Major clades typically corresponded to taxa occurring in the same biogeographic region, with two of them each occurring in Africa, South America and Asia. Because relationships among these major clades were poorly supported, more extensive molecular data sets are required to test the hypothesis of independent colonization and multiple dispersal events among these continents.}, } @article {pmid29103990, year = {2018}, author = {Caballero Van Dyke, MC and Wormley, FL}, title = {A Call to Arms: Quest for a Cryptococcal Vaccine.}, journal = {Trends in microbiology}, volume = {26}, number = {5}, pages = {436-446}, pmid = {29103990}, issn = {1878-4380}, support = {R01 AI071752/AI/NIAID NIH HHS/United States ; R25 GM060655/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Antigens, Fungal/immunology ; Cryptococcosis/*immunology/*prevention & control ; Cryptococcus gattii/immunology/pathogenicity ; Cryptococcus neoformans/immunology/pathogenicity ; Disease Models, Animal ; Fungal Proteins/immunology ; *Fungal Vaccines ; Glycolipids/immunology ; Humans ; Recombinant Proteins/immunology ; Vaccination ; Vaccines, Attenuated/immunology ; Vaccines, Inactivated/immunology ; Vaccines, Synthetic/immunology ; }, abstract = {Cryptococcosis remains a significant cause of morbidity and mortality world-wide, particularly among AIDS patients. Yet, to date, there are no licensed vaccines clinically available to treat or prevent cryptococcosis. In this review, we provide a rationale to support continued investment in Cryptococcus vaccine research, potential challenges that must be overcome along the way, and a literature review of the current progress underway towards developing a vaccine to prevent cryptococcosis.}, } @article {pmid29103876, year = {2018}, author = {Minkina, O and Hunter, CP}, title = {Intergenerational Transmission of Gene Regulatory Information in Caenorhabditis elegans.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {54-64}, pmid = {29103876}, issn = {0168-9525}, support = {R01 GM089795/GM/NIGMS NIH HHS/United States ; }, mesh = {Animals ; Animals, Genetically Modified ; Caenorhabditis elegans/*genetics ; *Epigenesis, Genetic ; Gene Expression Regulation ; Gene Silencing ; Inheritance Patterns ; Stress, Physiological/*genetics ; }, abstract = {Epigenetic mechanisms can stably maintain gene expression states even after the initiating conditions have changed. Often epigenetic information is transmitted only to daughter cells, but evidence is emerging, in both vertebrate and invertebrate systems, for transgenerational epigenetic inheritance (TEI), the transmission of epigenetic gene regulatory information across generations. Each new description of TEI helps uncover the properties, molecular mechanisms and biological roles for TEI. The nematode Caenorhabditis elegans has been particularly instrumental in the effort to understand TEI, as multiple environmental and genetic triggers can initiate an epigenetic signal that can alter the expression of both transgenes and endogenous loci. Here, we review recent studies of TEI in C. elegans.}, } @article {pmid29103761, year = {2018}, author = {Lindenmayer, DB and Likens, GE and Franklin, JF}, title = {Earth Observation Networks (EONs): Finding the Right Balance.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {1}, pages = {1-3}, doi = {10.1016/j.tree.2017.10.008}, pmid = {29103761}, issn = {1872-8383}, mesh = {*Earth (Planet) ; Environmental Monitoring/*methods ; }, abstract = {Earth observation networks (EONs) are an emerging, surveillance-based approach to environmental monitoring and research that are fundamentally different than traditional question-driven, experimentally designed approaches. There is an urgent need to find an optimal balance between these approaches and to develop new integrated initiatives that take advantage of key features of them both.}, } @article {pmid29102408, year = {2018}, author = {Gounand, I and Harvey, E and Little, CJ and Altermatt, F}, title = {Meta-Ecosystems 2.0: Rooting the Theory into the Field.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {1}, pages = {36-46}, doi = {10.1016/j.tree.2017.10.006}, pmid = {29102408}, issn = {1872-8383}, mesh = {Ecology/*methods ; *Ecosystem ; *Meta-Analysis as Topic ; *Models, Biological ; }, abstract = {The meta-ecosystem framework demonstrates the significance of among-ecosystem spatial flows for ecosystem dynamics and has fostered a rich body of theory. The high level of abstraction of the models, however, impedes applications to empirical systems. We argue that further understanding of spatial dynamics in natural systems strongly depends on dense exchanges between field and theory. From empiricists, more and specific quantifications of spatial flows are needed, defined by the major categories of organismal movement (dispersal, foraging, life-cycle, and migration). In parallel, the theoretical framework must account for the distinct spatial scales at which these naturally common spatial flows occur. Integrating all levels of spatial connections among landscape elements will upgrade and unify landscape and meta-ecosystem ecology into a single framework for spatial ecology.}, } @article {pmid29102406, year = {2018}, author = {McLaughlin, CN and Broihier, HT}, title = {Keeping Neurons Young and Foxy: FoxOs Promote Neuronal Plasticity.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {65-78}, pmid = {29102406}, issn = {0168-9525}, support = {R01 NS095895/NS/NINDS NIH HHS/United States ; R21 NS090369/NS/NINDS NIH HHS/United States ; }, mesh = {Animals ; Caenorhabditis elegans Proteins/genetics ; Cytoskeleton/metabolism ; Drosophila Proteins/genetics/metabolism ; Forkhead Transcription Factors/*genetics/metabolism ; Humans ; Neural Stem Cells/*physiology ; Neuronal Plasticity/*physiology ; Neurons/cytology/physiology ; Synapses/physiology ; }, abstract = {Any adult who has tried to take up the piano or learn a new language is faced with the sobering realization that acquiring such skills is more challenging as an adult than as a child. Neuronal plasticity, or the malleability of brain circuits, declines with age. Young neurons tend to be more adaptable and can alter the size and strength of their connections more readily than can old neurons. Myriad circuit- and synapse-level mechanisms that shape plasticity have been identified. Yet, molecular mechanisms setting the overall competence of young neurons for distinct forms of plasticity remain largely obscure. Recent studies indicate evolutionarily conserved roles for FoxO proteins in establishing the capacity for cell-fate, morphological, and synaptic plasticity in neurons.}, } @article {pmid29101453, year = {2018}, author = {Anisha, C and Sachidanandan, P and Radhakrishnan, EK}, title = {Endophytic Paraconiothyrium sp. from Zingiber officinale Rosc. Displays Broad-Spectrum Antimicrobial Activity by Production of Danthron.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {343-352}, pmid = {29101453}, issn = {1432-0991}, support = {order no: SR/S9/Z-23/2010/22//Department of Science and Technology, Government of India, under DST-PURSE program/ ; }, mesh = {Anthraquinones/chemistry/metabolism/*pharmacology ; Anti-Infective Agents/chemistry/metabolism/*pharmacology ; Ascomycota/*chemistry/genetics/metabolism ; Endophytes/*chemistry/genetics/metabolism ; Fungal Proteins/genetics/metabolism ; Gas Chromatography-Mass Spectrometry ; Ginger/*microbiology ; Humans ; Plant Diseases/parasitology ; Pythiosis/parasitology ; Pythium/drug effects ; }, abstract = {The bioactivity spectrum of fungal endophytes isolated from Zingiber officinale was analyzed against clinical pathogens and against the phytopathogen Pythium myriotylum, which causes Pythium rot in ginger. One of the isolates GFM13 showed broad bioactivity against various pathogens tested including P. myriotylum. The spore suspension as well as the culture filtrate of the endophytic fungal isolate was found to effectively protect ginger rhizomes from Pythium rot. By molecular identification, the fungal endophyte was identified as Paraconiothyrium sp. The bioactive compound produced by the isolate was separated by bioactivity-guided fractionation and was identified by GC-MS as danthron, an anthraquinone derivative. PCR amplification showed the presence of non-reducing polyketide synthase gene (NR-PKS) in the endophyte GFM13, which is reported to be responsible for the synthesis of anthraquinones in fungi. This is the first report of danthron being produced as the biologically active component of Paraconiothyrium sp. Danthron is reported to have wide pharmaceutical and agronomic applications which include its use as a fungicide in agriculture. The broad-spectrum antimicrobial activity of danthron and the endophytic origin of Paraconiothyrium sp. offer immense applications of the study.}, } @article {pmid29101107, year = {2018}, author = {Waldmann, TA}, title = {Cytokines in Cancer Immunotherapy.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {12}, pages = {}, doi = {10.1101/cshperspect.a028472}, pmid = {29101107}, issn = {1943-0264}, abstract = {Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints. To circumvent these impediments, cytokines are being investigated clinically in combination therapy with checkpoint inhibitors, anticancer monoclonal antibodies to increase the antibody-dependent cellular cytotoxicity (ADCC) of these antibodies, antibody cytokine fusion proteins, and anti-CD40 to facilitate tumor-specific immune responses.}, } @article {pmid29100657, year = {2018}, author = {Cheng, LC and Tu, KC and Seidel, CW and Robb, SMC and Guo, F and Sánchez Alvarado, A}, title = {Cellular, ultrastructural and molecular analyses of epidermal cell development in the planarian Schmidtea mediterranea.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {357-373}, pmid = {29100657}, issn = {1095-564X}, support = {R37 GM057260/GM/NIGMS NIH HHS/United States ; }, mesh = {Animal Structures/ultrastructure ; Animals ; Antibodies, Helminth/immunology ; Cell Differentiation/genetics ; Cell Lineage ; Cell Movement ; *Epidermal Cells ; Epidermis/metabolism/radiation effects/ultrastructure ; Gene Expression Regulation, Developmental ; Gene Ontology ; Genes, Helminth ; Helminth Proteins/genetics/immunology/*physiology ; Mesoderm/cytology ; Microscopy, Electron ; Multigene Family ; Organelles/ultrastructure ; Planarians/*cytology/metabolism/ultrastructure ; RNA Interference ; Transcription Factors/physiology ; }, abstract = {The epidermis is essential for animal survival, providing both a protective barrier and cellular sensor to external environments. The generally conserved embryonic origin of the epidermis, but the broad morphological and functional diversity of this organ across animals is puzzling. We define the transcriptional regulators underlying epidermal lineage differentiation in the planarian Schmidtea mediterranea, an invertebrate organism that, unlike fruitflies and nematodes, continuously replaces its epidermal cells. We find that Smed-p53, Sox and Pax transcription factors are essential regulators of epidermal homeostasis, and act cooperatively to regulate genes associated with early epidermal precursor cell differentiation, including a tandemly arrayed novel gene family (prog) of secreted proteins. Additionally, we report on the discovery of distinct and previously undescribed secreted organelles whose production is dependent on the transcriptional activity of soxP-3, and which we term Hyman vesicles.}, } @article {pmid29100109, year = {2018}, author = {Baldwin, PR and Tan, YZ and Eng, ET and Rice, WJ and Noble, AJ and Negro, CJ and Cianfrocco, MA and Potter, CS and Carragher, B}, title = {Big data in cryoEM: automated collection, processing and accessibility of EM data.}, journal = {Current opinion in microbiology}, volume = {43}, number = {}, pages = {1-8}, pmid = {29100109}, issn = {1879-0364}, support = {P41 GM103310/GM/NIGMS NIH HHS/United States ; R01 GM099678/GM/NIGMS NIH HHS/United States ; }, mesh = {Automation, Laboratory/instrumentation ; *Big Data ; Cloud Computing ; Cryoelectron Microscopy/*methods/statistics & numerical data ; }, abstract = {The scope and complexity of cryogenic electron microscopy (cryoEM) data has greatly increased, and will continue to do so, due to recent and ongoing technical breakthroughs that have led to much improved resolutions for macromolecular structures solved using this method. This big data explosion includes single particle data as well as tomographic tilt series, both generally acquired as direct detector movies of ∼10-100 frames per image or per tilt-series. We provide a brief survey of the developments leading to the current status, and describe existing cryoEM pipelines, with an emphasis on the scope of data acquisition, methods for automation, and use of cloud storage and computing.}, } @article {pmid29099937, year = {2018}, author = {Brandini, S and Bergamaschi, P and Cerna, MF and Gandini, F and Bastaroli, F and Bertolini, E and Cereda, C and Ferretti, L and Gómez-Carballa, A and Battaglia, V and Salas, A and Semino, O and Achilli, A and Olivieri, A and Torroni, A}, title = {The Paleo-Indian Entry into South America According to Mitogenomes.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {299-311}, pmid = {29099937}, issn = {1537-1719}, abstract = {Recent and compelling archaeological evidence attests to human presence ∼14.5 ka at multiple sites in South America and a very early exploitation of extreme high-altitude Andean environments. Considering that, according to genetic evidence, human entry into North America from Beringia most likely occurred ∼16 ka, these archeological findings would imply an extremely rapid spread along the double continent. To shed light on this issue from a genetic perspective, we first completely sequenced 217 novel modern mitogenomes of Native American ancestry from the northwestern area of South America (Ecuador and Peru); we then evaluated them phylogenetically together with other available mitogenomes (430 samples, both modern and ancient) from the same geographic area and, finally, with all closely related mitogenomes from the entire double continent. We detected a large number (N = 48) of novel subhaplogroups, often branching into further subclades, belonging to two classes: those that arose in South America early after its peopling and those that instead originated in North or Central America and reached South America with the first settlers. Coalescence age estimates for these subhaplogroups provide time boundaries indicating that early Paleo-Indians probably moved from North America to the area corresponding to modern Ecuador and Peru over the short time frame of ∼1.5 ka comprised between 16.0 and 14.6 ka.}, } @article {pmid29099354, year = {2018}, author = {Zhang, Q and Oh, M and Kim, JH and Kanjanasuntree, R and Konkit, M and Sukhoom, A and Kantachote, D and Kim, W}, title = {Arthrobacter paludis sp. nov., isolated from a marsh.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {47-51}, doi = {10.1099/ijsem.0.002426}, pmid = {29099354}, issn = {1466-5034}, mesh = {Arthrobacter/*classification/genetics/isolation & purification ; Bacterial Typing Techniques ; Base Composition ; Cell Wall/chemistry ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; *Wetlands ; }, abstract = {A novel Gram-stain-positive, strictly aerobic, non-endospore-forming bacterium, designated CAU 9143T, was isolated from a hydric soil sample collected from Seogmo Island in the Republic of Korea. Strain CAU 9143T grew optimally at 30 °C, at pH 7.0 and in the presence of 1 % (w/v) NaCl. The phylogenetic trees based on 16S rRNA gene sequences revealed that strain CAU 9143T belonged to the genus Arthrobacter and was closely related to Arthrobacter ginkgonis SYP-A7299T (97.1 % similarity). Strain CAU 9143T contained menaquinone MK-9 (H2) as the major respiratory quinone and diphosphatidylglycerol, phosphatidylglycerol, phosphatidylinositol, two glycolipids and two unidentified phospholipids as the major polar lipids. The whole-cell sugars were glucose and galactose. The peptidoglycan type was A4a (l-Lys-D-Glu2) and the major cellular fatty acid was anteiso-C15 : 0. The DNA G+C content was 64.4 mol% and the level of DNA-DNA relatedness between CAU 9143T and the most closely related strain, A. ginkgonis SYP-A7299T, was 22.3 %. Based on phenotypic, chemotaxonomic and genetic data, strain CAU 9143T represents a novel species of the genus Arthrobacter, for which the name Arthrobacterpaludis sp. nov. is proposed. The type strain is CAU 9143T (=KCTC 13958T,=CECT 8917T).}, } @article {pmid29099353, year = {2018}, author = {de Vries, SPW and Hadjirin, NF and Lay, EM and Zadoks, RN and Peacock, SJ and Parkhill, J and Grant, AJ and McDougall, S and Holmes, MA}, title = {Streptococcus bovimastitidis sp. nov., isolated from a dairy cow with mastitis.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {21-27}, doi = {10.1099/ijsem.0.002321}, pmid = {29099353}, issn = {1466-5034}, support = {G1001787//Medical Research Council/United Kingdom ; }, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Cattle ; DNA, Bacterial/genetics ; Female ; Mastitis, Bovine/*microbiology ; New Zealand ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Streptococcal Infections/*veterinary ; Streptococcus/*classification/genetics/isolation & purification ; }, abstract = {Here we describe a new species of the genus Streptococcus that was isolated from a dairy cow with mastitis in New Zealand. Strain NZ1587T was Gram-positive, coccus-shaped and arranged as chains, catalase and coagulase negative, γ-haemolytic and negative for Lancefield carbohydrates (A-D, F and G). The 16S rRNA sequence did not match sequences in the NCBI 16S rRNA or GreenGenes databases. Taxonomic classification of strain NZ1587T was investigated using 16S rRNA and core genome phylogeny, genome-wide average nucleotide identity (ANI) and predicted DNA-DNA hybridisation (DDH) analyses. Phylogeny based on 16S rRNA was unable to resolve the taxonomic position of strain NZ1587T, however NZ1587T shared 99.4 % identity at the 16S rRNA level with a distinct branch of S. pseudoporcinus. Importantly, core genome phylogeny demonstrated that NZ1587T grouped amongst the 'pyogenic' streptococcal species and formed a distinct branch supported by a 100 % bootstrap value. In addition, average nucleotide identity and inferred DNA-DNA hybridisation analyses showed that NZ1587T represents a novel species. Biochemical profiling using the rapid ID 32 strep identification test enabled differentiation of strain NZ1587T from closely related streptococcal species. In conclusion, strain NZ1587T can be classified as a novel species, and we propose a novel taxon named Streptococcus bovimastitidis sp. nov.; the type strain is NZ1587T. NZ1587T has been deposited in the Culture Collection University of Gothenburg (CCUG 69277T) and the Belgian Co-ordinated Collections of Micro-organisms/LMG (LMG 29747).}, } @article {pmid29098761, year = {2018}, author = {Astudillo-García, C and Slaby, BM and Waite, DW and Bayer, K and Hentschel, U and Taylor, MW}, title = {Phylogeny and genomics of SAUL, an enigmatic bacterial lineage frequently associated with marine sponges.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {561-576}, doi = {10.1111/1462-2920.13965}, pmid = {29098761}, issn = {1462-2920}, abstract = {Many marine sponges contain dense and diverse communities of associated microorganisms. Members of the 'sponge-associated unclassified lineage' (SAUL) are frequently recorded from sponges, yet little is known about these bacteria. Here we investigated the distribution and phylogenetic status of SAUL. A meta-analysis of the available literature revealed the widespread distribution of this clade and its association with taxonomically varied sponge hosts. Phylogenetic analyses, conducted using both 16S rRNA gene-based phylogeny and concatenated marker protein sequences, revealed that SAUL is a sister clade of the candidate phylum 'Latescibacteria'. Furthermore, we conducted a comprehensive analysis of two draft genomes assembled from sponge metagenomes, revealing novel insights into the physiology of this symbiont. Metabolic reconstruction suggested that SAUL members are aerobic bacteria with facultative anaerobic metabolism, with the capacity to degrade multiple sponge- and algae-derived carbohydrates. We described for the first time in a sponge symbiont the putative genomic capacity to transport phosphate into the cell and to produce and store polyphosphate granules, presumably constituting a phosphate reservoir for the sponge host in deprivation periods. Our findings suggest that the lifestyle of SAUL is symbiotic with the host sponge, and identify symbiont factors which may facilitate the establishment and maintenance of this relationship.}, } @article {pmid29098691, year = {2018}, author = {Shahandeh, MP and Pischedda, A and Turner, TL}, title = {Male mate choice via cuticular hydrocarbon pheromones drives reproductive isolation between Drosophila species.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {123-135}, pmid = {29098691}, issn = {1558-5646}, support = {R01 GM098614/GM/NIGMS NIH HHS/United States ; }, abstract = {Mate discrimination is a key mechanism restricting gene flow between species. While studied extensively with respect to female mate choice, mechanisms of male mate choice between species are far less studied. Thus, we have little knowledge of the relative frequency, importance, or overall contribution of male mate discrimination to reproductive isolation. In the present study, we estimated the relative contributions of male and female choice to reproductive isolation between Drosophila simulans and D. sechellia, and show that male mate discrimination accounts for the majority of the current isolation between these species. We further demonstrate that males discriminate based on female cuticular hydrocarbon pheromones, and collect evidence supporting the hypothesis that male mate discrimination may alleviate the costs associated with heterospecific courtship and mating. Our findings highlight the potentially significant contribution of male mate choice to the formation of reproductive isolating barriers, and thus the speciation process.}, } @article {pmid29098686, year = {2018}, author = {Rose, NH and Bay, RA and Morikawa, MK and Palumbi, SR}, title = {Polygenic evolution drives species divergence and climate adaptation in corals.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {82-94}, doi = {10.1111/evo.13385}, pmid = {29098686}, issn = {1558-5646}, abstract = {Closely related species often show substantial differences in ecological traits that allow them to occupy different environmental niches. For few of these systems is it clear what the genomic basis of adaptation is and whether a few loci of major effect or many genome-wide differences drive species divergence. Four cryptic species of the tabletop coral Acropora hyacinthus are broadly sympatric in American Samoa; here we show that two common species have differences in key environmental traits such as microhabitat distributions and thermal stress tolerance. We compared gene expression patterns and genetic polymorphism between these two species using RNA-Seq. The vast majority of polymorphisms are shared between species, but the two species show widespread differences in allele frequencies and gene expression, and tend to host different symbiont types. We find that changes in gene expression are related to changes in the frequencies of many gene regulatory variants, but that many of these differences are consistent with the action of genetic drift. However, we observe greater genetic divergence between species in amino acid replacement polymorphisms compared to synonymous variants. These findings suggest that polygenic evolution plays a major role in driving species differences in ecology and resilience to climate change.}, } @article {pmid29098371, year = {2018}, author = {Jiang, X and Overdeep, KR and Wainwright, ER and Weihs, TP and Mao, HQ}, title = {Effect of Humidity on Sporicidal Activity of Iodine Vapor on Bacillus thuringiensis.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {237-246}, pmid = {29098371}, issn = {1432-0991}, support = {HDTRA1-11-1-0063//Defense Threat Reduction Agency/ ; }, mesh = {Anti-Infective Agents, Local/*pharmacology ; Bacillus anthracis ; Bacillus thuringiensis/*drug effects ; Colony Count, Microbial ; *Humidity ; Iodine/*pharmacology ; Microbial Viability/drug effects ; Spores, Bacterial/*drug effects ; Temperature ; }, abstract = {The emergence of Bacillus anthracis as a potential bioterrorism and biological warfare agent points to the need for safe, effective, and economical sporicides for infection prevention and control. This work examined the efficacy of iodine vapor decontamination technologies to inactivate a surrogate for B. anthracis, Bacillus thuringiensis spores on glass materials. 106-107 colony-forming units of spores inoculated onto circular glass cover slips were treated with different concentrations of iodine vapor under various temperature and relative humidity. Only minimal spore killing activity was observed at low humidity. Higher humidity levels, as well as pre-hydration or post-hydration of the spores, increased the rate of inactivation as long as the contact between spores and iodine was maintained in a hydrated environment. Significant sporicidal activity of 3-log and 6-log spore reduction has been observed with 2.1 mg L-1 iodine vapor concentration at 90% relative humidity and 22 °C, with 1 and 24 h of exposure, respectively. The results showed that the relative humidity of the environment is of major importance in regulating the rate at which the spores are inactivated by iodine. The results of this study may provide insight into the parameters of effective decontamination procedures for Bacillus spores using gaseous iodine.}, } @article {pmid29097494, year = {2018}, author = {Routy, B and Le Chatelier, E and Derosa, L and Duong, CPM and Alou, MT and Daillère, R and Fluckiger, A and Messaoudene, M and Rauber, C and Roberti, MP and Fidelle, M and Flament, C and Poirier-Colame, V and Opolon, P and Klein, C and Iribarren, K and Mondragón, L and Jacquelot, N and Qu, B and Ferrere, G and Clémenson, C and Mezquita, L and Masip, JR and Naltet, C and Brosseau, S and Kaderbhai, C and Richard, C and Rizvi, H and Levenez, F and Galleron, N and Quinquis, B and Pons, N and Ryffel, B and Minard-Colin, V and Gonin, P and Soria, JC and Deutsch, E and Loriot, Y and Ghiringhelli, F and Zalcman, G and Goldwasser, F and Escudier, B and Hellmann, MD and Eggermont, A and Raoult, D and Albiges, L and Kroemer, G and Zitvogel, L}, title = {Gut microbiome influences efficacy of PD-1-based immunotherapy against epithelial tumors.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {91-97}, doi = {10.1126/science.aan3706}, pmid = {29097494}, issn = {1095-9203}, support = {P30 CA008748/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Anti-Bacterial Agents/therapeutic use ; Antibodies, Monoclonal/therapeutic use ; CD4 Antigens/immunology ; *Fecal Microbiota Transplantation ; Feces/microbiology ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; Immunotherapy/*methods ; Interleukin-12/immunology ; Metagenome/genetics ; Mice ; Neoplasms/*therapy ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; Receptors, CCR/immunology ; Receptors, CXCR3/immunology ; T-Lymphocytes/immunology ; Verrucomicrobia/genetics/immunology ; }, abstract = {Immune checkpoint inhibitors (ICIs) targeting the PD-1/PD-L1 axis induce sustained clinical responses in a sizable minority of cancer patients. We found that primary resistance to ICIs can be attributed to abnormal gut microbiome composition. Antibiotics inhibited the clinical benefit of ICIs in patients with advanced cancer. Fecal microbiota transplantation (FMT) from cancer patients who responded to ICIs into germ-free or antibiotic-treated mice ameliorated the antitumor effects of PD-1 blockade, whereas FMT from nonresponding patients failed to do so. Metagenomics of patient stool samples at diagnosis revealed correlations between clinical responses to ICIs and the relative abundance of Akkermansia muciniphila Oral supplementation with A. muciniphila after FMT with nonresponder feces restored the efficacy of PD-1 blockade in an interleukin-12-dependent manner by increasing the recruitment of CCR9+CXCR3+CD4+ T lymphocytes into mouse tumor beds.}, } @article {pmid29097493, year = {2018}, author = {Gopalakrishnan, V and Spencer, CN and Nezi, L and Reuben, A and Andrews, MC and Karpinets, TV and Prieto, PA and Vicente, D and Hoffman, K and Wei, SC and Cogdill, AP and Zhao, L and Hudgens, CW and Hutchinson, DS and Manzo, T and Petaccia de Macedo, M and Cotechini, T and Kumar, T and Chen, WS and Reddy, SM and Szczepaniak Sloane, R and Galloway-Pena, J and Jiang, H and Chen, PL and Shpall, EJ and Rezvani, K and Alousi, AM and Chemaly, RF and Shelburne, S and Vence, LM and Okhuysen, PC and Jensen, VB and Swennes, AG and McAllister, F and Marcelo Riquelme Sanchez, E and Zhang, Y and Le Chatelier, E and Zitvogel, L and Pons, N and Austin-Breneman, JL and Haydu, LE and Burton, EM and Gardner, JM and Sirmans, E and Hu, J and Lazar, AJ and Tsujikawa, T and Diab, A and Tawbi, H and Glitza, IC and Hwu, WJ and Patel, SP and Woodman, SE and Amaria, RN and Davies, MA and Gershenwald, JE and Hwu, P and Lee, JE and Zhang, J and Coussens, LM and Cooper, ZA and Futreal, PA and Daniel, CR and Ajami, NJ and Petrosino, JF and Tetzlaff, MT and Sharma, P and Allison, JP and Jenq, RR and Wargo, JA}, title = {Gut microbiome modulates response to anti-PD-1 immunotherapy in melanoma patients.}, journal = {Science (New York, N.Y.)}, volume = {359}, number = {6371}, pages = {97-103}, pmid = {29097493}, issn = {1095-9203}, support = {P30 CA016672/CA/NCI NIH HHS/United States ; R25 CA057730/CA/NCI NIH HHS/United States ; R25 CA056452/CA/NCI NIH HHS/United States ; UL1 TR000128/TR/NCATS NIH HHS/United States ; K12 CA088084/CA/NCI NIH HHS/United States ; K08 CA160692/CA/NCI NIH HHS/United States ; }, mesh = {Animals ; Fecal Microbiota Transplantation ; Gastrointestinal Microbiome/genetics/*immunology ; Humans ; *Immunotherapy ; Melanoma/immunology/*therapy ; Metagenome ; Mice ; Programmed Cell Death 1 Receptor/*antagonists & inhibitors ; Skin Neoplasms/immunology/*therapy ; }, abstract = {Preclinical mouse models suggest that the gut microbiome modulates tumor response to checkpoint blockade immunotherapy; however, this has not been well-characterized in human cancer patients. Here we examined the oral and gut microbiome of melanoma patients undergoing anti-programmed cell death 1 protein (PD-1) immunotherapy (n = 112). Significant differences were observed in the diversity and composition of the patient gut microbiome of responders versus nonresponders. Analysis of patient fecal microbiome samples (n = 43, 30 responders, 13 nonresponders) showed significantly higher alpha diversity (P < 0.01) and relative abundance of bacteria of the Ruminococcaceae family (P < 0.01) in responding patients. Metagenomic studies revealed functional differences in gut bacteria in responders, including enrichment of anabolic pathways. Immune profiling suggested enhanced systemic and antitumor immunity in responding patients with a favorable gut microbiome as well as in germ-free mice receiving fecal transplants from responding patients. Together, these data have important implications for the treatment of melanoma patients with immune checkpoint inhibitors.}, } @article {pmid29097091, year = {2018}, author = {Bowen, WH and Burne, RA and Wu, H and Koo, H}, title = {Oral Biofilms: Pathogens, Matrix, and Polymicrobial Interactions in Microenvironments.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {229-242}, pmid = {29097091}, issn = {1878-4380}, support = {R01 DE012236/DE/NIDCR NIH HHS/United States ; R01 DE025220/DE/NIDCR NIH HHS/United States ; R01 DE018023/DE/NIDCR NIH HHS/United States ; R01 DE025832/DE/NIDCR NIH HHS/United States ; R01 DE022350/DE/NIDCR NIH HHS/United States ; }, mesh = {*Biofilms ; Cellular Microenvironment/*physiology ; Dental Caries/*microbiology ; Dental Plaque/microbiology ; Dietary Sugars ; Host-Pathogen Interactions ; Humans ; Microbial Interactions ; *Microbiota ; Virulence ; }, abstract = {Biofilms are microbial communities embedded within an extracellular matrix, forming a highly organized structure that causes many human infections. Dental caries (tooth decay) is a polymicrobial biofilm disease driven by the diet and microbiota-matrix interactions that occur on a solid surface. Sugars fuel the emergence of pathogens, the assembly of the matrix, and the acidification of the biofilm microenvironment, promoting ecological changes and concerted multispecies efforts that are conducive to acid damage of the mineralized tooth tissue. Here, we discuss recent advances in the role of the biofilm matrix and interactions between opportunistic pathogens and commensals in the pathogenesis of dental caries. In addition, we highlight the importance of matrix-producing organisms in fostering a pathogenic habitat where interspecies competition and synergies occur to drive the disease process, which could have implications to other infections associated with polymicrobial biofilms.}, } @article {pmid29097090, year = {2018}, author = {Morris, DH and Gostic, KM and Pompei, S and Bedford, T and Łuksza, M and Neher, RA and Grenfell, BT and Lässig, M and McCauley, JW}, title = {Predictive Modeling of Influenza Shows the Promise of Applied Evolutionary Biology.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {102-118}, pmid = {29097090}, issn = {1878-4380}, support = {R35 GM119774/GM/NIGMS NIH HHS/United States ; P2C HD047879/HD/NICHD NIH HHS/United States ; R01 AI127893/AI/NIAID NIH HHS/United States ; P01 CA087497/CA/NCI NIH HHS/United States ; F31 AI134017/AI/NIAID NIH HHS/United States ; MC_U117512723//Medical Research Council/United Kingdom ; //Wellcome Trust/United Kingdom ; FC001030//Cancer Research UK/United Kingdom ; FC001030//Medical Research Council/United Kingdom ; FC001030//Wellcome Trust/United Kingdom ; }, mesh = {Antigens, Viral/genetics/immunology ; *Biological Evolution ; Decision Support Techniques ; Disease Outbreaks ; *Forecasting ; Hemagglutination Inhibition Tests/methods ; Humans ; *Influenza Vaccines/immunology ; *Influenza, Human/epidemiology/genetics/prevention & control/virology ; Orthomyxoviridae/genetics/immunology ; Public Health ; Seasons ; Vaccination ; World Health Organization ; }, abstract = {Seasonal influenza is controlled through vaccination campaigns. Evolution of influenza virus antigens means that vaccines must be updated to match novel strains, and vaccine effectiveness depends on the ability of scientists to predict nearly a year in advance which influenza variants will dominate in upcoming seasons. In this review, we highlight a promising new surveillance tool: predictive models. Based on data-sharing and close collaboration between the World Health Organization and academic scientists, these models use surveillance data to make quantitative predictions regarding influenza evolution. Predictive models demonstrate the potential of applied evolutionary biology to improve public health and disease control. We review the state of influenza predictive modeling and discuss next steps and recommendations to ensure that these models deliver upon their considerable biomedical promise.}, } @article {pmid29096889, year = {2018}, author = {Brodersen, J and Post, DM and Seehausen, O}, title = {Upward Adaptive Radiation Cascades: Predator Diversification Induced by Prey Diversification.}, journal = {Trends in ecology & evolution}, volume = {33}, number = {1}, pages = {59-70}, doi = {10.1016/j.tree.2017.09.016}, pmid = {29096889}, issn = {1872-8383}, mesh = {Animals ; *Biodiversity ; *Biological Evolution ; *Food Chain ; *Predatory Behavior ; }, abstract = {The value of biodiversity is widely appreciated, but we are only beginning to understand the interplay of processes that generate biodiversity and their consequences for coevolutionary interactions. Whereas predator-prey coevolution is most often analyzed in the context of evolutionary arms races, much less has been written about how predators are affected by, and respond to, evolutionary diversification in their prey. We hypothesize here that adaptive radiation of prey may lead to diversification and potentially speciation in predators, a process that we call an upwards adaptive radiation cascade. In this paper we lay out the conceptual basis for upwards adaptive radiation cascades, explore evidence for such cascades, and finally advocate for intensified research.}, } @article {pmid29095141, year = {2018}, author = {Moya, G and Yan, ZF and Chu, DH and Won, K and Yang, JE and Wang, QJ and Kook, MC and Yi, TH}, title = {Deinococcus hibisci sp. nov., isolated from rhizosphere of Hibiscus syriacus L. (mugunghwa flower).}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {28-34}, doi = {10.1099/ijsem.0.002405}, pmid = {29095141}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; Deinococcus/*classification/genetics/isolation & purification ; Fatty Acids/chemistry ; Glycolipids/chemistry ; Hibiscus/*microbiology ; Nucleic Acid Hybridization ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; *Rhizosphere ; Sequence Analysis, DNA ; *Soil Microbiology ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, pink-pigmented, coccus-shaped, strictly aerobic, non-motile bacterium, strain THG-AG1.5T, was isolated from rhizosphere of Hibiscus syriacus L. (Mugunghwa flower) located in Kyung Hee University, Yongin, Gyeonggi, Republic of Korea. The isolated strain grew optimally at 25-30 °C, at pH 6.0-7.5 and in the presence of additional 0-1.5 % (w/v) NaCl. Strain THG-AG1.5T exhibited tolerance to UV radiation (>1500 J m-2) and to gamma radiation (>12 kGy). Based on 16S rRNA gene sequence comparisons, strain THG-AG1.5T was closely related to Deinococcus daejeonensis MJ27T (98.03 %), Deinococcus radiotolerans C1T (97.61 %) and Deinococcus grandis DSM 3963T (97.32 %). The genomic DNA G+C content of strain THG-AG1.5T was 74.8 mol%. The DNA-DNA hybridization values between strain THG-AG1.5T and its closest phylogenetically neighbours were below 63.0 %. The peptidoglycan amino acids were alanine, valine, glutamic acid, glycine, ornithine, lysine and aspartic acid. Strain THG-AG1.5T contained ribose, mannose and glucose as whole-cell-wall sugars and menaquinone-8 (MK-8) as the only isoprenoid quinone. The major component in the polyamine pattern was spermidine. The major polar lipids of strain THG-AG1.5T were a phosphoglycolipid, six unidentified glycolipids and an unidentified aminophospholipid. The major fatty acids were identified as iso-C15 : 0, C15 : 1ω6c, C16 : 0, iso-C17 : 0, C17 : 0, C18 : 0 and summed feature 3. On the basis of our polyphasic taxonomy study, strain THG-AG1.5T represents a novel species within the genus Deinococcus, for which the name Deinococcushibisci sp. nov. is proposed. The type strain is THG-AG1.5T (=KACC 18850T=CCTCC AB 2016078T).}, } @article {pmid29095140, year = {2018}, author = {Kämpfer, P and Rückert, C and Blom, J and Goesmann, A and Wink, J and Kalinowski, J and Glaeser, SP}, title = {Streptomyces ciscaucasicus Sveshnikova et al. 1983 is a later subjective synonym of Streptomyces canus Heinemann et al. 1953.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {42-46}, doi = {10.1099/ijsem.0.002418}, pmid = {29095140}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Multilocus Sequence Typing ; *Phylogeny ; Sequence Analysis, DNA ; Streptomyces/*classification ; }, abstract = {Streptomyces canuswas described in 1953 and the name was listed in the Approved List of Bacterial Names in 1980. Three years later, Streptomyces ciscaucasicus was published and the name was subsequently validated in Validation List no. 22 in 1986. On the basis of genome comparison and multilocus sequence analysis of the type strains of Streptomyces canus and Streptomyces ciscaucasicus it can now be shown that these two species despite some phenotypic differences are subjective synonyms. In such a case Rule 24 of the Bacteriological Code applies, in which priority of names is determined by the date of the original publication. Hence, we propose that S. ciscaucasicus is a later subjective synonym of S. canus.}, } @article {pmid29095138, year = {2018}, author = {Fan, MC and Nan, LJ and Zhu, YM and Chen, WM and Wei, GH and Lin, YB}, title = {Mitsuaria noduli sp. nov., isolated from the root nodules of Robinia pseudoacacia in a lead-zinc mine.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {87-92}, doi = {10.1099/ijsem.0.002459}, pmid = {29095138}, issn = {1466-5034}, mesh = {Bacterial Typing Techniques ; Base Composition ; Burkholderiales/*classification/genetics/isolation & purification ; China ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Lead ; *Mining ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Robinia/*microbiology ; Root Nodules, Plant/*microbiology ; Sequence Analysis, DNA ; *Soil Microbiology ; Ubiquinone/chemistry ; Zinc ; }, abstract = {A novel endophytic bacterium, designated strain HZ7T, was isolated from the root nodules of Robinia pseudoacacia growing in a lead-zinc mine in Mianxian County, Shaanxi Province, China. Cells were Gram-reaction-negative, aerobic, motile, rod-shaped, methyl-red-negative, catalase-positive, positive for chitosan-degrading activity and did not produce H2S. Strain HZ7T grew at 4-45 °C (optimum 25-30 °C), at pH 5-9 (optimum pH 7-8) and with 0-1 % (w/v) NaCl. The quinone type was ubiquinone 8 (UQ-8). The major fatty acids were identified as C16 : 0, C17 : 0 cyclo and summed feature 3 (C16 : 1ω7c and/or C16 : 1ω6c). The G+C content of the genomic DNA was 68.5 mol% by whole genome sequencing. According to 16S rRNA gene sequence analysis, the closest phylogenetic relative was Mitsuaria chitosanitabida 3001T (99.05 % similarity). Genome relatedness was computed using average nucleotide identity and genome-to-genome distance analysis, both of which strongly supported strain HZ7Tas belonging to the genus Mitsuaria as a representative of a novel species. On the basis of phylogenetic analysis, chemotaxonomic data and physiological characteristics, strain HZ7T represents a novel species of the genus Mitsuaria, for which the name Mitsuaria noduli sp. nov. is proposed. The type strain is HZ7T (=JCM 31671T=CCTCC AB 2014353T).}, } @article {pmid29095137, year = {2018}, author = {Martina, P and Leguizamon, M and Prieto, CI and Sousa, SA and Montanaro, P and Draghi, WO and Stämmler, M and Bettiol, M and de Carvalho, CCCR and Palau, J and Figoli, C and Alvarez, F and Benetti, S and Lejona, S and Vescina, C and Ferreras, J and Lasch, P and Lagares, A and Zorreguieta, A and Leitão, JH and Yantorno, OM and Bosch, A}, title = {Burkholderia puraquae sp. nov., a novel species of the Burkholderia cepacia complex isolated from hospital settings and agricultural soils.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {14-20}, doi = {10.1099/ijsem.0.002293}, pmid = {29095137}, issn = {1466-5034}, mesh = {Agriculture ; Bacterial Typing Techniques ; Base Composition ; Burkholderia cepacia complex/*classification ; Cystic Fibrosis/*microbiology ; DNA, Bacterial/genetics ; Fatty Acids/chemistry ; Genes, Bacterial ; Humans ; Multilocus Sequence Typing ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; *Soil Microbiology ; Species Specificity ; Sputum ; }, abstract = {Bacteria from the Burkholderia cepacia complex (Bcc) are capable of causing severe infections in patients with cystic fibrosis (CF). These opportunistic pathogens are also widely distributed in natural and man-made environments. After a 12-year epidemiological surveillance involving Bcc bacteria from respiratory secretions of Argentinean patients with CF and from hospital settings, we found six isolates of the Bcc with a concatenated species-specific allele sequence that differed by more than 3 % from those of the Bcc with validly published names. According to the multilocus sequence analysis (MLSA), these isolates clustered with the agricultural soil strain, Burkholderia sp. PBP 78, which was already deposited in the PubMLST database. The isolates were examined using a polyphasic approach, which included 16S rRNA, recA, Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), DNA base composition, average nucleotide identities (ANIs), fatty acid profiles, and biochemical characterizations. The results of the present study demonstrate that the seven isolates represent a single novel species within the Bcc, for which the name Burkholderia puraquae sp. nov. is proposed. Burkholderia puraquae sp. nov. CAMPA 1040T (=LMG 29660T=DSM 103137T) was designated the type strain of the novel species, which can be differentiated from other species of the Bcc mainly from recA gene sequence analysis, MLSA, ANIb, MALDI-TOF MS analysis, and some biochemical tests, including the ability to grow at 42 °C, aesculin hydrolysis, and lysine decarboxylase and β-galactosidase activities.}, } @article {pmid29095136, year = {2018}, author = {Liu, Y and Lai, Q and Shao, Z}, title = {Genome analysis-based reclassification of Bacillus weihenstephanensis as a later heterotypic synonym of Bacillus mycoides.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {106-112}, doi = {10.1099/ijsem.0.002466}, pmid = {29095136}, issn = {1466-5034}, mesh = {Bacillus/*classification ; Bacterial Typing Techniques ; DNA, Bacterial/genetics ; Genes, Bacterial ; Multilocus Sequence Typing ; Nucleic Acid Hybridization ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The aim of this study was to clarify the taxonomic status of the species Bacillus weihenstephanensis. A complete genome sequence for the type strain of B. weihenstephanensis was compared against that of the closely related type strain of Bacillus mycoides. The digital DNA-DNA hybridization and average nucleotide identity values between the two type strains was greater than two recognized thresholds for bacterial species delineation, indicating that they should belong to the same genomospecies. The psychrotolerant characteristic and signature sequences of 16S rRNA and cspA genes were incapable of distinguishing B. weihenstephanensis from some non-B. weihenstephanensis strains. Meanwhile, the metabolic, physiological and chemotaxonomic features for the type strain of B. weihenstephanensis were shown to be congruent with those of B. mycoides. On this basis, the taxonomic affiliations of related strains from the Genbank database were determined using multilocus sequence typing and genomic analyses. Therefore, we propose Bacillus weihenstephanensis as a later heterotypic synonym of Bacillus mycoides and correction of erroneous species identifications for several strains.}, } @article {pmid29094423, year = {2018}, author = {Stone, JD and Olson, MS}, title = {Pollination context alters female advantage in gynodioecious Silene vulgaris.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {111-122}, doi = {10.1111/jeb.13203}, pmid = {29094423}, issn = {1420-9101}, mesh = {Animals ; Phenotype ; *Pollination ; Reproduction ; Seeds/physiology ; Silene/*physiology ; }, abstract = {Gynodioecy, the co-occurrence of females and hermaphrodites, is arguably the most common angiosperm gender polymorphism in many florae. Females' ability to invade and persist among hermaphrodites depends, in part, on pollinators providing adequate pollination to females. We directly measured diurnal and nocturnal pollinators' contributions to female and hermaphrodite seed production in artificial populations of gynodioecious Silene vulgaris by experimentally restricting pollinator access. We found that female relative seed production in this system depended strongly on pollination context: females produced more than twice as many seeds as hermaphrodites in the context of abundant, nectar-collecting moths. Conversely, females showed no seed production advantage in the context of pollen-collecting syrphid flies and bees due to acutely hermaphrodite-biased visitation. We infer that variation in pollinator type, behaviour and abundance may be important for achieving the female relative fitness thresholds necessary for the maintenance of gynodioecy. Generally, our study illustrates how pollinator-mediated mechanisms may influence the evolution of breeding systems and associated suites of floral traits. Segments of a pollinator community may facilitate gynodioecy by selecting for plant characteristics that increase the attractiveness of both sexes to pollinators, such as nectar rewards. Conversely, discriminating visitors in search of pollen may restrict gynodioecy in associated plant lineages by reducing male steriles' fitness below threshold levels.}, } @article {pmid29094340, year = {2018}, author = {Sweet, AD and Boyd, BM and Allen, JM and Villa, SM and Valim, MP and Rivera-Parra, JL and Wilson, RE and Johnson, KP}, title = {Integrating phylogenomic and population genomic patterns in avian lice provides a more complete picture of parasite evolution.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {95-112}, doi = {10.1111/evo.13386}, pmid = {29094340}, issn = {1558-5646}, abstract = {Parasite diversity accounts for most of the biodiversity on earth, and is shaped by many processes (e.g., cospeciation, host switching). To identify the effects of the processes that shape parasite diversity, it is ideal to incorporate both deep (phylogenetic) and shallow (population) perspectives. To this end, we developed a novel workflow to obtain phylogenetic and population genetic data from whole genome sequences of body lice parasitizing New World ground-doves. Phylogenies from these data showed consistent, highly resolved species-level relationships for the lice. By comparing the louse and ground-dove phylogenies, we found that over long-term evolutionary scales their phylogenies were largely congruent. Many louse lineages (both species and populations) also demonstrated high host-specificity, suggesting ground-dove divergence is a primary driver of their parasites' diversity. However, the few louse taxa that are generalists are structured according to biogeography at the population level. This suggests dispersal among sympatric hosts has some effect on body louse diversity, but over deeper time scales the parasites eventually sort according to host species. Overall, our results demonstrate that multiple factors explain the patterns of diversity in this group of parasites, and that the effects of these factors can vary over different evolutionary scales. The integrative approach we employed was crucial for uncovering these patterns, and should be broadly applicable to other studies.}, } @article {pmid29092069, year = {2018}, author = {Pathmanathan, JS and Lopez, P and Lapointe, FJ and Bapteste, E}, title = {CompositeSearch: A Generalized Network Approach for Composite Gene Families Detection.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {252-255}, pmid = {29092069}, issn = {1537-1719}, abstract = {Genes evolve by point mutations, but also by shuffling, fusion, and fission of genetic fragments. Therefore, similarity between two sequences can be due to common ancestry producing homology, and/or partial sharing of component fragments. Disentangling these processes is especially challenging in large molecular data sets, because of computational time. In this article, we present CompositeSearch, a memory-efficient, fast, and scalable method to detect composite gene families in large data sets (typically in the range of several million sequences). CompositeSearch generalizes the use of similarity networks to detect composite and component gene families with a greater recall, accuracy, and precision than recent programs (FusedTriplets and MosaicFinder). Moreover, CompositeSearch provides user-friendly quality descriptions regarding the distribution and primary sequence conservation of these gene families allowing critical biological analyses of these data.}, } @article {pmid29092048, year = {2018}, author = {Roy, SW}, title = {Intragenomic Conflict and Immune Tolerance: Do Selfish X-Linked Alleles Drive Skewed X Chromosome Inactivation?.}, journal = {Genome biology and evolution}, volume = {10}, number = {3}, pages = {857-862}, pmid = {29092048}, issn = {1759-6653}, mesh = {Alleles ; Alzheimer Disease/genetics ; Chromosomes, Human, X/*genetics/immunology ; *Evolution, Molecular ; Female ; Genes, X-Linked/genetics/immunology ; Humans ; Immune Tolerance/*genetics/immunology ; Pregnancy ; X Chromosome Inactivation/*genetics/immunology ; }, abstract = {In mammalian females, diploid somatic cells contain two X chromosomes, one of which is transcriptionally silenced, in a process termed X chromosome inactivation (XCI). Whereas XCI is largely random in placental females, many women exhibit skewed XCI (SXCI), in which the vast majority cells have the same X chromosome inactivated. SXCI has serious health consequences, associated with conditions ranging from Alzheimer's to various autoimmune disorders. SXCI is also associated with outcomes of pregnancies, with higher rates of recurrent spontaneous abortion in women with SXCI. Here, I suggest that SXCI could be driven by selfish X-linked alleles. Consistent with the association of SXCI with autoimmunity, I first note the possibility that recurrent spontaneous abortion could reflect immune rejection of fetuses inheriting alleles from the largely silenced maternal X chromosome. Preferential abortion of fetuses carrying silenced X-linked alleles implies a transmission advantage for X-linked alleles on the largely expressed chromosome, which could drive the emergence of X-linked alleles that make the chromosome resistant to XCI. I discuss the evolutionary dynamics, fitness tradeoffs and implications of this hypothesis, and suggest future directions.}, } @article {pmid29090323, year = {2018}, author = {Lee, GE and Im, WT and Park, JS}, title = {Vibrio hannami sp. nov., Isolated from Seawater.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {278-283}, pmid = {29090323}, issn = {1432-0991}, support = {2016R1D1A3B03933067//and by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (2016R1D1A3B03933067)/ ; }, mesh = {Bacterial Typing Techniques ; Base Composition ; DNA, Bacterial/genetics ; DNA, Ribosomal/genetics ; Fatty Acids/chemistry/metabolism ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Seawater/*microbiology ; Vibrio/classification/genetics/*isolation & purification/metabolism ; }, abstract = {A Gram-reaction negative, aerobic, motile, non-pigmented and rod-shaped bacterium, designated as 168GH5-2-16T, was isolated from seawater Jeju island. Phylogenetic analysis based on 16S rRNA gene sequence comparison revealed that the strain formed a distinct lineage within the genus Vibrio and was most closely related to Vibrio variabilis R-40492T (96.0%). The DNA G+C content was 49.3 mol%. The major polar lipids were phosphatidylethanolamine (PE) and phosphatidylglycerol (PG). The predominant quinone was ubiquinone-8 (Q-8). The major fatty acids were C16:0, summed feature 3 (comprising C16:1 ω7c/C16:1 ω6c) and summed feature 8 (C18:1 ω7c/C18:1 ω6c) supported the affiliation of 168GH5-2-16T to the genus Vibrio. Moreover, the physiological, biochemical, and taxonomic analysis allowed the phenotypic and genotypic differentiation of strain 168GH5-2-16T from the recognized species of the genus Vibrio. Therefore, strain 168GH5-2-16T represents a novel species of the genus Vibrio, for which the name Vibrio hannami sp. nov. is proposed, with the type strain 168GH5-2-16T (=KACC 19277T = DSM105032T).}, } @article {pmid29090322, year = {2018}, author = {Jiang, J and Liu, Y and Liu, Y and Hou, S}, title = {A Novel ZnONPs/PVA-Functionalized Biomaterials for Bacterial Cells Immobilization and its Strengthening Effects on Quinoline Biodegradation.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {316-322}, pmid = {29090322}, issn = {1432-0991}, support = {15JF021//Science and Technology Industrialization Project/ ; 2012GS610203//the Project of Science and Technology Benefit Plan/ ; }, mesh = {Biocompatible Materials/chemistry/metabolism ; Biodegradation, Environmental ; Cells, Immobilized/chemistry/metabolism ; Nanoparticles/chemistry ; Ochrobactrum/*chemistry/*metabolism ; Polyvinyl Alcohol/chemistry ; Quinolines/chemistry/*metabolism ; Water Pollutants, Chemical/chemistry/metabolism ; Zinc Oxide/chemistry ; }, abstract = {A novel bacterial cells immobilized carrier (ZnONPs/PVA), polyvinyl alcohol (PVA) composites decorated with ZnO nanoparticles (ZnO NPs), was prepared and used for immobilization of the strain Ochrobactrum sp. LC-1, and subsequently for quinoline degrading in water. Characterization of ZnONPs/PVA by using X-ray diffractometer and scanning electron microscopy demonstrated that ZnO NPs were coated on the surface of PVA cubes evenly and the bacterium grew well on the ZnONPs/PVA. Quinoline biodegradation results showed that the degradation effect of quinoline by ZnONPs/PVA immobilized cells was superior to the free cells significantly. The structure and physical properties of ZnNPs/PVA were maintained steady after the reuse of ZnNPs/PVA for cells immobilization several times. Reusability of the ZnONPs/PVA immobilized cells revealed that the quinoline removal ratio was above 97% within 8 h under the conditions of pH neutral, 37 °C when the initial quinoline concentration was 300 mg/L.}, } @article {pmid29089182, year = {2018}, author = {Silva-Barrios, S and Charpentier, T and Stäger, S}, title = {The Deadly Dance of B Cells with Trypanosomatids.}, journal = {Trends in parasitology}, volume = {34}, number = {2}, pages = {155-171}, doi = {10.1016/j.pt.2017.10.001}, pmid = {29089182}, issn = {1471-5007}, support = {MOP-123293//CIHR/Canada ; }, mesh = {B-Lymphocytes/*immunology/*parasitology ; Chronic Disease ; Host-Parasite Interactions/*immunology ; Humans ; Leishmania/*immunology ; Leishmaniasis/*immunology/parasitology ; Trypanosoma/*immunology ; Trypanosomiasis/*immunology/parasitology ; }, abstract = {B cells are notorious actors for the host's protection against several infectious diseases. So much so that early vaccinology seated its principles upon their long-term protective antibody secretion capabilities. Indeed, there are many examples of acute infectious diseases that are combated by functional humoral responses. However, some chronic infectious diseases actively induce immune deregulations that often lead to defective, if not deleterious, humoral immune responses. In this review we summarize how Leishmania and Trypanosoma spp. directly manipulate B cell responses to induce polyclonal B cell activation, hypergammaglobulinemia, low-specificity antibodies, limited B cell survival, and regulatory B cells, contributing therefore to immunopathology and the establishment of persistent infections.}, } @article {pmid29089173, year = {2018}, author = {Turroni, F and Milani, C and Duranti, S and Mahony, J and van Sinderen, D and Ventura, M}, title = {Glycan Utilization and Cross-Feeding Activities by Bifidobacteria.}, journal = {Trends in microbiology}, volume = {26}, number = {4}, pages = {339-350}, doi = {10.1016/j.tim.2017.10.001}, pmid = {29089173}, issn = {1878-4380}, abstract = {Bifidobacteria represent one of the first colonizers of the mammalian gut, where such colonization is facilitated by their saccharolytic capabilities. Genomic analyses of bifidobacteria have revealed intriguing genetic strategies employed by these bacteria to access a variety of dietary and host-produced glycans. Bifidobacterial genome evolution therefore represents a fascinating example of how their chromosomes were molded to contain a large number of genes involved in carbohydrate metabolism. One of the reasons as to why bifidobacteria are such dominant and prevalent members of the (early) microbiota is that they may access glycans in the gut through mutualistic cross-feeding or resource-sharing activities, which is indicative of 'social behavior' among bifidobacterial strains.}, } @article {pmid29087519, year = {2018}, author = {Zeng, L and Ming, C and Li, Y and Su, LY and Su, YH and Otecko, NO and Dalecky, A and Donnellan, S and Aplin, K and Liu, XH and Song, Y and Zhang, ZB and Esmailizadeh, A and Sohrabi, SS and Nanaei, HA and Liu, HQ and Wang, MS and Ag Atteynine, S and Rocamora, G and Brescia, F and Morand, S and Irwin, DM and Peng, MS and Yao, YG and Li, HP and Wu, DD and Zhang, YP}, title = {Out of Southern East Asia of the Brown Rat Revealed by Large-Scale Genome Sequencing.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {149-158}, doi = {10.1093/molbev/msx276}, pmid = {29087519}, issn = {1537-1719}, abstract = {The geographic origin and migration of the brown rat (Rattus norvegicus) remain subjects of considerable debate. In this study, we sequenced whole genomes of 110 wild brown rats with a diverse world-wide representation. We reveal that brown rats migrated out of southern East Asia, rather than northern Asia as formerly suggested, into the Middle East and then to Europe and Africa, thousands of years ago. Comparison of genomes from different geographical populations reveals that many genes involved in the immune system experienced positive selection in the wild brown rat.}, } @article {pmid29087487, year = {2018}, author = {Shi, CM and Yang, Z}, title = {Coalescent-Based Analyses of Genomic Sequence Data Provide a Robust Resolution of Phylogenetic Relationships among Major Groups of Gibbons.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {159-179}, pmid = {29087487}, issn = {1537-1719}, support = {BB/P006493/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The phylogenetic relationships among extant gibbon species remain unresolved despite numerous efforts using morphological, behavorial, and genetic data and the sequencing of whole genomes. A major challenge in reconstructing the gibbon phylogeny is the radiative speciation process, which resulted in extremely short internal branches in the species phylogeny and extensive incomplete lineage sorting with extensive gene-tree heterogeneity across the genome. Here, we analyze two genomic-scale data sets, with ∼10,000 putative noncoding and exonic loci, respectively, to estimate the species tree for the major groups of gibbons. We used the Bayesian full-likelihood method bpp under the multispecies coalescent model, which naturally accommodates incomplete lineage sorting and uncertainties in the gene trees. For comparison, we included three heuristic coalescent-based methods (mp-est, SVDQuartets, and astral) as well as concatenation. From both data sets, we infer the phylogeny for the four extant gibbon genera to be (Hylobates, (Nomascus, (Hoolock, Symphalangus))). We used simulation guided by the real data to evaluate the accuracy of the methods used. Astral, while not as efficient as bpp, performed well in estimation of the species tree even in presence of excessive incomplete lineage sorting. Concatenation, mp-est and SVDQuartets were unreliable when the species tree contains very short internal branches. Likelihood ratio test of gene flow suggests a small amount of migration from Hylobates moloch to H. pileatus, while cross-genera migration is absent or rare. Our results highlight the utility of coalescent-based methods in addressing challenging species tree problems characterized by short internal branches and rampant gene tree-species tree discordance.}, } @article {pmid29087461, year = {2018}, author = {Blau, K and Casadevall, L and Wolters, B and Van den Meersche, T and Kreuzig, R and Smalla, K and Jechalke, S}, title = {Soil texture-depending effects of doxycycline and streptomycin applied with manure on the bacterial community composition and resistome.}, journal = {FEMS microbiology ecology}, volume = {94}, number = {2}, pages = {}, doi = {10.1093/femsec/fix145}, pmid = {29087461}, issn = {1574-6941}, abstract = {Veterinary antibiotics, bacteria carrying antibiotic resistance determinants located on mobile genetic elements and nutrients are spread on agricultural soil using manure as fertilizer. However, systematic quantitative studies linking antibiotic concentrations and antimicrobial resistance genes (ARGs) in manure and the environment are scarce but needed to assess environmental risks. In this microcosm study, a sandy and a loamy soil were mixed with manure spiked with streptomycin or doxycycline at five concentrations. Total-community DNA was extracted on days 28 and 92, and the abundances of ARGs (aadA, strA, tet(A), tet(M), tet(W), tet(Q), sul1, qacE/qacEΔ1) and class 1 and 2 integron integrase genes (intI1 and intI2) were determined by qPCR relative to 16S rRNA genes. Effects on the bacterial community composition were evaluated by denaturing gradient gel electrophoresis of 16S rRNA gene amplicons. Manure application to the soils strongly increased the relative abundance of most tested genes. Antibiotics caused further enrichments which decreased over time and were mostly seen at high concentrations. Strikingly, the effects on relative gene abundances and soil bacterial community composition were more pronounced in sandy soil. The concept of defining antibiotic threshold concentrations for environmental risk assessments remains challenging due to the various influencing factors.}, } @article {pmid29085996, year = {2018}, author = {Zhang, Y and Su, X and Harris, AJ and Caraballo-Ortiz, MA and Ren, Z and Zhong, Y}, title = {Genetic Structure of the Bacterial Endosymbiont Buchnera aphidicola from Its Host Aphid Schlechtendalia chinensis and Evolutionary Implications.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {309-315}, pmid = {29085996}, issn = {1432-0991}, support = {2014AA021802//the National High Technology Research and Development "863" Program/ ; }, mesh = {Animals ; Aphids/*microbiology/physiology ; Buchnera/classification/*genetics/*isolation & purification/physiology ; China ; DNA, Bacterial/genetics ; *Evolution, Molecular ; Genetic Variation ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; *Symbiosis ; }, abstract = {Buchnera aphidicola is a primary symbiotic bacterium which provides essential amino acids to aphids. In this study, we sequenced nuclear 16s rDNA and atpAGD genes for 156 individuals of B. aphidicola from eight geographically distant populations to investigate the genetic diversity and structure of B. aphidicola associated to the sumac gall aphid Schlechtendalia chinensis in central and southern China. Our analyses of the combined sequences showed that B. aphidicola from S. chinensis had high haplotype and nucleotide diversity (h = 0.893; π = 0.00164). One of the 16 haplotypes detected had a wide geographic distribution across the central and southern China and was probably the ancestral haplotype of B. aphidicola from S. chinensis. A network and phylogenetic analysis revealed a geographic structure in which the 16 haplotypes of B. aphidicola were divided into the northern and southern clades separated by the Yangtze River. The two clades diverged from each other at 22.1 ± 3.7 Mya according to our divergence time estimations. Therefore, the modern genetic structure in B. aphidicola from S. chinensis has been probably impacted by historical geological events. Combined with the data from GenBank, we also reconstructed the phylogenetic relationships of three aphid subfamilies and their symbiont bacteria. The results indicated significant topological correlations between the aphid and bacterial phylogenies at interspecific levels.}, } @article {pmid29085995, year = {2018}, author = {Schmidt, JM and Henken, S and Dowd, SE and McLaughlin, RW}, title = {Analysis of the Microbial Diversity in the Fecal Material of Giraffes.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {323-327}, pmid = {29085995}, issn = {1432-0991}, mesh = {Animals ; Bacteria/classification/genetics/*isolation & purification ; *Biodiversity ; DNA, Bacterial/genetics ; DNA, Fungal/genetics ; Feces/*microbiology ; Fungi/classification/genetics/*isolation & purification ; Giraffes/microbiology ; *Microbiota ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; }, abstract = {Using bacterial and fungal tag-encoded FLX-Titanium amplicon pyrosequencing, the microbiota of the fecal material of seven giraffes living in captivity at the Jacksonville Zoo and Gardens, Jacksonville, FL was investigated. In all samples, the most predominant bacterial phylum was the Firmicutes followed by Bacteroidetes. The most predominant fungi were members of the phylum Ascomycota followed by Neocallimastigomycota in five of seven samples. The reverse was true in the other two samples.}, } @article {pmid29085077, year = {2018}, author = {Baran, N and Goldin, S and Maidanik, I and Lindell, D}, title = {Quantification of diverse virus populations in the environment using the polony method.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {62-72}, pmid = {29085077}, issn = {2058-5276}, mesh = {Bacteriophages/*classification/genetics ; DNA Viruses/genetics ; Ecosystem ; Genes, Viral ; Genome, Viral/genetics ; Indian Ocean ; Metagenomics/*methods ; *Phylogeny ; Prochlorococcus/*virology ; Seawater/*virology ; Sequence Analysis, DNA ; Synechococcus/*virology ; }, abstract = {Viruses are globally abundant and extremely diverse in their genetic make-up and in the hosts they infect. Although they influence the abundance, diversity and evolution of their hosts, current methods are inadequate for gaining a quantitative understanding of their impact on these processes. Here we report the adaptation of the solid-phase single-molecule PCR polony method for the quantification of taxonomically relevant groups of diverse viruses. Using T7-like cyanophages as our model, we found the polony method to be far superior to regular quantitative PCR methods and droplet digital PCR when degenerate primers were used to encompass the group's diversity. This method revealed that T7-like cyanophages were highly abundant in the Red Sea in spring 2013, reaching 770,000 phages ml-1, and displaying a similar depth distribution pattern to cyanobacteria. Furthermore, the abundances of two major clades within the T7-like cyanophages differed dramatically throughout the water column: clade B phages that carry the psbA photosynthesis gene and infect either Synechococcus or Prochlorococcus were at least 20-fold more abundant than clade A phages that lack psbA and infect Synechococcus hosts. Such measurements are of paramount importance for understanding virus population dynamics and the impact of viruses on different microbial taxa and for modelling viral influence on ecosystem functioning on a global scale.}, } @article {pmid29085076, year = {2018}, author = {Ofir, G and Melamed, S and Sberro, H and Mukamel, Z and Silverman, S and Yaakov, G and Doron, S and Sorek, R}, title = {DISARM is a widespread bacterial defence system with broad anti-phage activities.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {90-98}, pmid = {29085076}, issn = {2058-5276}, support = {681203//European Research Council/International ; T32 HG000044/HG/NHGRI NIH HHS/United States ; }, mesh = {Bacillus subtilis/*genetics/*virology ; Bacterial Proteins/genetics/*metabolism ; Bacteriophages/classification/growth & development/*physiology ; Cloning, Molecular ; Computational Biology ; DNA Restriction-Modification Enzymes/*genetics ; Genome, Bacterial/genetics ; Genomic Islands ; Methyltransferases/genetics ; Models, Genetic ; Multigene Family/*genetics ; Sequence Deletion ; Virus Replication ; }, abstract = {The evolutionary pressure imposed by phage predation on bacteria and archaea has resulted in the development of effective anti-phage defence mechanisms, including restriction-modification and CRISPR-Cas systems. Here, we report on a new defence system, DISARM (defence island system associated with restriction-modification), which is widespread in bacteria and archaea. DISARM is composed of five genes, including a DNA methylase and four other genes annotated as a helicase domain, a phospholipase D (PLD) domain, a DUF1998 domain and a gene of unknown function. Engineering the Bacillus paralicheniformis 9945a DISARM system into Bacillus subtilis has rendered the engineered bacteria protected against phages from all three major families of tailed double-stranded DNA phages. Using a series of gene deletions, we show that four of the five genes are essential for DISARM-mediated defence, with the fifth (PLD) being redundant for defence against some of the phages. We further show that DISARM restricts incoming phage DNA and that the B. paralicheniformis DISARM methylase modifies host CCWGG motifs as a marker of self DNA akin to restriction-modification systems. Our results suggest that DISARM is a new type of multi-gene restriction-modification module, expanding the arsenal of defence systems known to be at the disposal of prokaryotes against their viruses.}, } @article {pmid29085075, year = {2018}, author = {Vidakovic, L and Singh, PK and Hartmann, R and Nadell, CD and Drescher, K}, title = {Dynamic biofilm architecture confers individual and collective mechanisms of viral protection.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {26-31}, pmid = {29085075}, issn = {2058-5276}, support = {716734//European Research Council/International ; }, mesh = {Bacteriophage T7/physiology ; Biofilms/*growth & development ; Escherichia coli/growth & development/*physiology/virology ; Escherichia coli Proteins/genetics/*metabolism ; Extracellular Matrix/genetics/*metabolism ; Kinetics ; Single-Cell Analysis ; }, abstract = {In nature, bacteria primarily live in surface-attached, multicellular communities, termed biofilms 1-6 . In medical settings, biofilms cause devastating damage during chronic and acute infections; indeed, bacteria are often viewed as agents of human disease 7 . However, bacteria themselves suffer from diseases, most notably in the form of viral pathogens termed bacteriophages 8-12 , which are the most abundant replicating entities on Earth. Phage-biofilm encounters are undoubtedly common in the environment, but the mechanisms that determine the outcome of these encounters are unknown. Using Escherichia coli biofilms and the lytic phage T7 as models, we discovered that an amyloid fibre network of CsgA (curli polymer) protects biofilms against phage attack via two separate mechanisms. First, collective cell protection results from inhibition of phage transport into the biofilm, which we demonstrate in vivo and in vitro. Second, CsgA fibres protect cells individually by coating their surface and binding phage particles, thereby preventing their attachment to the cell exterior. These insights into biofilm-phage interactions have broad-ranging implications for the design of phage applications in biotechnology, phage therapy and the evolutionary dynamics of phages with their bacterial hosts.}, } @article {pmid29082913, year = {2018}, author = {Bartha, I and di Iulio, J and Venter, JC and Telenti, A}, title = {Human gene essentiality.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {51-62}, pmid = {29082913}, issn = {1471-0064}, mesh = {Animals ; *Genes, Essential ; Genetic Variation ; Genome, Human ; Genomics ; Haploinsufficiency ; Humans ; Mice ; Mice, Knockout ; RNA, Untranslated/genetics ; }, abstract = {A gene can be defined as essential when loss of its function compromises viability of the individual (for example, embryonic lethality) or results in profound loss of fitness. At the population level, identification of essential genes is accomplished by observing intolerance to loss-of-function variants. Several computational methods are available to score gene essentiality, and recent progress has been made in defining essentiality in the non-coding genome. Haploinsufficiency is emerging as a critical aspect of gene essentiality: approximately 3,000 human genes cannot tolerate loss of one of the two alleles. Genes identified as essential in human cell lines or knockout mice may be distinct from those in living humans. Reconciling these discrepancies in how we evaluate gene essentiality has applications in clinical genetics and may offer insights for drug development.}, } @article {pmid29082465, year = {2018}, author = {Zamudio, GS and José, MV}, title = {Phenotypic Graphs and Evolution Unfold the Standard Genetic Code as the Optimal.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {83-91}, doi = {10.1007/s11084-017-9552-3}, pmid = {29082465}, issn = {1573-0875}, support = {PAPIIT-IN224015//DGAPA UNAM/ ; 737920//CONACYT/ ; }, mesh = {*Evolution, Molecular ; *Genetic Code ; *Models, Genetic ; }, abstract = {In this work, we explicitly consider the evolution of the Standard Genetic Code (SGC) by assuming two evolutionary stages, to wit, the primeval RNY code and two intermediate codes in between. We used network theory and graph theory to measure the connectivity of each phenotypic graph. The connectivity values are compared to the values of the codes under different randomization scenarios. An error-correcting optimal code is one in which the algebraic connectivity is minimized. We show that the SGC is optimal in regard to its robustness and error-tolerance when compared to all random codes under different assumptions.}, } @article {pmid29081496, year = {2018}, author = {Petrova, VN and Russell, CA}, title = {The evolution of seasonal influenza viruses.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {47-60}, pmid = {29081496}, issn = {1740-1534}, mesh = {Animals ; Antigenic Variation/genetics/immunology ; *Biological Evolution ; Evolution, Molecular ; Genetic Variation ; Global Health ; Host-Pathogen Interactions/immunology ; Humans ; Influenza Vaccines/immunology ; Influenza, Human/epidemiology/immunology/prevention & control/*virology ; Orthomyxoviridae/classification/*physiology ; *Seasons ; }, abstract = {Despite decades of surveillance and pharmaceutical and non-pharmaceutical interventions, seasonal influenza viruses continue to cause epidemics around the world each year. The key process underlying these recurrent epidemics is the evolution of the viruses to escape the immunity that is induced by prior infection or vaccination. Although we are beginning to understand the processes that underlie the evolutionary dynamics of seasonal influenza viruses, the timing and nature of emergence of new virus strains remain mostly unpredictable. In this Review, we discuss recent advances in understanding the molecular determinants of influenza virus immune escape, sources of evolutionary selection pressure, population dynamics of influenza viruses and prospects for better influenza virus control.}, } @article {pmid29080673, year = {2018}, author = {Noguerales, V and Cordero, PJ and Ortego, J}, title = {Inferring the demographic history of an oligophagous grasshopper: Effects of climatic niche stability and host-plant distribution.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {343-356}, doi = {10.1016/j.ympev.2017.10.012}, pmid = {29080673}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Climate Change ; DNA/isolation & purification/metabolism ; Ecosystem ; Electron Transport Complex IV/chemistry/genetics ; France ; *Genetic Variation ; Genetics, Population ; Grasshoppers/classification/*genetics ; Linkage Disequilibrium ; Phylogeny ; Phylogeography ; }, abstract = {Understanding the consequences of past environmental changes on the abiotic and biotic components of the landscape and deciphering their impacts on the demographic trajectories of species is a major issue in evolutionary biogeography. In this study, we combine nuclear and mitochondrial genetic data to study the phylogeographical structure and lineage-specific demographic histories of the scrub-legume grasshopper (Chorthippus binotatus binotatus), a montane taxon distributed in the Iberian Peninsula and France that exclusively feeds on certain scrub-legume species. Genetic data and paleo-distribution modelling indicate the presence of four main lineages that seem to have diverged in allopatry and long-term persisted in Iberian and French refugia since the Mid Pleistocene. Comparisons of different demographic hypotheses in an Approximate Bayesian Computation (ABC) framework supported a population bottleneck in the northwestern French clade and paleo-distribution modelling indicate that the populations of this lineage have experienced more severe environmental fluctuations during the last 21 000 years than those from the Iberian Peninsula. Accordingly, we found that nuclear genetic diversity of the populations of scrub-legume grasshopper is positively associated with local stability of suitable habitats defined by both Pleistocene climate changes and historical distributional shifts of host-plant species. Overall, our study highlights the importance of integrating the potential effects of abiotic (i.e. climate and geography) and biotic components (i.e. inter-specific interactions) into the study of the evolutionary and demographic history of specialist taxa with narrow ecological requirements.}, } @article {pmid29080390, year = {2018}, author = {Shine, R and Wapstra, E and Olsson, M}, title = {Seasonal shifts along the oviparity-viviparity continuum in a cold-climate lizard population.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {4-13}, doi = {10.1111/jeb.13202}, pmid = {29080390}, issn = {1420-9101}, mesh = {Animals ; Body Size/physiology ; *Cold Temperature ; Female ; Lizards/*physiology ; Oviparity/*physiology ; Seasons ; Sweden ; Viviparity, Nonmammalian/*physiology ; }, abstract = {Squamate embryos require weeks of high temperature to complete development, with the result that cool climatic areas are dominated by viviparous taxa (in which gravid females can sun-bask to keep embryos warm) rather than oviparous taxa (which rely on warm soil to incubate their eggs). How, then, can some oviparous taxa reproduce successfully in cool climates - especially late in summer, when soil temperatures are falling? Near the northern limit of their distribution (in Sweden), sand lizards (Lacerta agilis) shift tactics seasonally, such that the eggs in late clutches complete development more quickly (when incubated at a standard temperature) than do those of early clutches. That acceleration is achieved by a reduction in egg size and by an increase in the duration of uterine retention of eggs (especially, after cool weather). Our results clarify the ability of oviparous reptiles to reproduce successfully in cool climates and suggest a novel advantage to reptilian viviparity in such conditions: by maintaining high body temperatures, viviparous females may escape the need to reduce offspring size in late-season litters.}, } @article {pmid29080375, year = {2018}, author = {Gotcha, N and Terblanche, JS and Nyamukondiwa, C}, title = {Plasticity and cross-tolerance to heterogeneous environments: divergent stress responses co-evolved in an African fruit fly.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {98-110}, doi = {10.1111/jeb.13201}, pmid = {29080375}, issn = {1420-9101}, mesh = {Animals ; *Biological Evolution ; Drosophila/*physiology ; *Environment ; Stress, Physiological/*physiology ; }, abstract = {Plastic adjustments of physiological tolerance to a particular stressor can result in fitness benefits for resistance that might manifest not only in that same environment but also be advantageous when faced with alternative environmental stressors, a phenomenon termed 'cross-tolerance'. The nature and magnitude of cross-tolerance responses can provide important insights into the underlying genetic architecture, potential constraints on or versatility of an organism's stress responses. In this study, we tested for cross-tolerance to a suite of abiotic factors that likely contribute to setting insect population dynamics and geographic range limits: heat, cold, desiccation and starvation resistance in adult Ceratitis rosa following acclimation to all these isolated individual conditions prior to stress assays. Traits of stress resistance scored included critical thermal (activity) limits, chill coma recovery time (CCRT), heat knockdown time (HKDT), desiccation and starvation resistance. In agreement with other studies, we found that acclimation to one stress typically increased resistance for that same stress experienced later in life. A more novel outcome, however, is that here we also found substantial evidence for cross-tolerance. For example, we found an improvement in heat tolerance (critical thermal maxima, CTmax) following starvation or desiccation hardening and improved desiccation resistance following cold acclimation, indicating pronounced cross-tolerance to these environmental stressors for the traits examined. We also found that two different traits of the same stress resistance differed in their responsiveness to the same stress conditions (e.g. HKDT was less cross-resistant than CTmax). The results of this study have two major implications that are of broader importance: (i) that these traits likely co-evolved to cope with diverse or simultaneous stressors, and (ii) that a set of common underlying physiological mechanisms might exist between apparently divergent stress responses in this species. This species may prove to be a valuable model for future work on the evolutionary and mechanistic basis of cross-tolerance.}, } @article {pmid29079499, year = {2018}, author = {Kumar, CS and Dey, D and Ghosh, S and Banerjee, M}, title = {Breach: Host Membrane Penetration and Entry by Nonenveloped Viruses.}, journal = {Trends in microbiology}, volume = {26}, number = {6}, pages = {525-537}, doi = {10.1016/j.tim.2017.09.010}, pmid = {29079499}, issn = {1878-4380}, abstract = {Disruption of host membranes by nonenveloped viruses, which allows the nucleocapsid or genome to enter the cytosol, is a mechanistically diverse process. Although the membrane-penetrating agents are usually small, hydrophobic or amphipathic peptides deployed from the capsid interior during entry, their manner of membrane interaction varies substantially. In this review, we discuss recent data about the molecular pathways for externalization of viral peptides amidst conformational alterations in the capsid, as well as mechanisms of membrane penetration, which is influenced by structural features of the peptides themselves as well as physicochemical properties of membranes, and other host factors. The membrane-penetrating components of nonenveloped viruses constitute an interesting class of cell-penetrating peptides, and may have potential therapeutic value for gene transfer.}, } @article {pmid29079498, year = {2018}, author = {Taylor, SL and McGuckin, MA and Wesselingh, S and Rogers, GB}, title = {Infection's Sweet Tooth: How Glycans Mediate Infection and Disease Susceptibility.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {92-101}, doi = {10.1016/j.tim.2017.09.011}, pmid = {29079498}, issn = {1878-4380}, mesh = {Adhesins, Bacterial ; Antibodies ; Bacteria/pathogenicity ; Bacterial Infections ; Communicable Diseases ; *Disease Susceptibility ; Fucosyltransferases/genetics/*metabolism ; Host-Pathogen Interactions ; Humans ; Microbiota ; Mucus/immunology/metabolism/microbiology ; Polysaccharides/*immunology/*metabolism ; Virus Diseases ; }, abstract = {Glycans form a highly variable constituent of our mucosal surfaces and profoundly affect our susceptibility to infection and disease. The diversity and importance of these surface glycans can be seen in individuals who lack a functional copy of the fucosyltransferase gene, FUT2. Representing around one-fifth of the population, these individuals have an altered susceptibility to many bacterial and viral infections and diseases. The mediation of host-pathogen interactions by mucosal glycans, such as those added by FUT2, is poorly understood. We highlight, with specific examples, important mechanisms by which host glycans influence infection dynamics, including by: acting as pathogen receptors (or receptor-decoys), promoting microbial stability, altering the physical characteristics of mucus, and acting as immunological markers. We argue that the effect glycans have on infection dynamics has profound implications for many aspects of healthcare and policy, including clinical management, outbreak control, and vaccination policy.}, } @article {pmid29079378, year = {2018}, author = {Yoshizawa, K and Johnson, KP and Sweet, AD and Yao, I and Ferreira, RL and Cameron, SL}, title = {Mitochondrial phylogenomics and genome rearrangements in the barklice (Insecta: Psocodea).}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {118-127}, doi = {10.1016/j.ympev.2017.10.014}, pmid = {29079378}, issn = {1095-9513}, mesh = {Animals ; Evolution, Molecular ; *Gene Order ; *Genome, Mitochondrial ; Insecta/*classification/*genetics ; Mitochondria/*genetics ; Molecular Sequence Annotation ; *Phylogeny ; Sequence Analysis, DNA ; }, abstract = {The mitochondrial genome arrangement in the insect order Psocodea (booklice, barklice, and parasitic lice) is extremely variable. Genome organization ranges from the rearrangement of a few tRNAs and protein coding genes, through extensive tRNA and protein coding gene rearrangements, to subdivision into multiple mini-chromosomes. Evolution of the extremely modified mitochondrial genome in parasitic lice (Phthiraptera) has been the subject of several studies, but limited information is available regarding the mitochondrial genome organization of the more plesiomorphic, free-living Psocodea (formerly known as the "Psocoptera"). In particular, the ancestral state of the psocodean mitochondrial genome arrangement and the evolutionary pathway to the rearranged conditions are still unknown. In this study, we addressed mitochondrial evolutionary questions within the Psocodea by using mitochondrial genome sequences obtained from a wide range of Psocoptera, covering all three suborders. We identified seven types of mitochondrial genome arrangements in Psocoptera, including the first example in Psocodea of retention of the ancestral pancrustacean condition in Prionoglaris (Prionoglarididae). Two methods (condition-based parsimony reconstruction and common-interval genome distances) were applied to estimate the ancestral mitochondrial arrangement in Psocodea, and both provided concordant results. Specifically, the common ancestor of Psocodea retained the ancestral pancrustacean condition, and most of the gene arrangement types have originated independently from this ancestral condition. We also utilized the genomic data for phylogenetic estimation. The tree estimated from the mitochondrial genomic data was well resolved, strongly supported, and in agreement with previously estimated phylogenies. It also provided the first robust support for the family Prionoglarididae, as its monophyly was uncertain in previous morphological and molecular studies.}, } @article {pmid29078204, year = {2018}, author = {Garcia, EC}, title = {Contact-dependent interbacterial toxins deliver a message.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {40-46}, pmid = {29078204}, issn = {1879-0364}, support = {K22 AI118949/AI/NIAID NIH HHS/United States ; }, mesh = {Bacteria/*metabolism ; Bacterial Proteins/metabolism ; Bacterial Toxins/*metabolism ; Biofilms/growth & development ; Burkholderia/metabolism ; Microbial Interactions/*physiology ; Signal Transduction ; Type VI Secretion Systems/metabolism ; }, abstract = {Both Gram-negative and Gram-positive organisms harbor systems for delivering toxins to neighboring bacteria upon direct cell contact. These systems, typified by type VI secretion (T6S) and contact-dependent growth inhibition (CDI) systems, are defined by their ability to mediate interbacterial competition in vitro, while their biological roles have remained uncertain. Recent research into the mechanisms of toxin delivery and activity, as well as investigation of contact-dependent toxin function during relevant biological processes, has offered insight into how interbacterial competition might work outside of the laboratory. Furthermore, non-competitive roles for contact-dependent toxin delivery systems, including interbacterial signal transduction, have been described. This review suggests that contact-dependent toxin delivery systems that exhibit functions beyond interbacterial competition are probably more common than currently appreciated.}, } @article {pmid29077934, year = {2018}, author = {Carter, CW and Wills, PR}, title = {Interdependence, Reflexivity, Fidelity, Impedance Matching, and the Evolution of Genetic Coding.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {269-286}, pmid = {29077934}, issn = {1537-1719}, support = {R01 GM078227/GM/NIGMS NIH HHS/United States ; }, abstract = {Genetic coding is generally thought to have required ribozymes whose functions were taken over by polypeptide aminoacyl-tRNA synthetases (aaRS). Two discoveries about aaRS and their interactions with tRNA substrates now furnish a unifying rationale for the opposite conclusion: that the key processes of the Central Dogma of molecular biology emerged simultaneously and naturally from simple origins in a peptide•RNA partnership, eliminating the epistemological utility of a prior RNA world. First, the two aaRS classes likely arose from opposite strands of the same ancestral gene, implying a simple genetic alphabet. The resulting inversion symmetries in aaRS structural biology would have stabilized the initial and subsequent differentiation of coding specificities, rapidly promoting diversity in the proteome. Second, amino acid physical chemistry maps onto tRNA identity elements, establishing reflexive, nanoenvironmental sensing in protein aaRS. Bootstrapping of increasingly detailed coding is thus intrinsic to polypeptide aaRS, but impossible in an RNA world. These notions underline the following concepts that contradict gradual replacement of ribozymal aaRS by polypeptide aaRS: 1) aaRS enzymes must be interdependent; 2) reflexivity intrinsic to polypeptide aaRS production dynamics promotes bootstrapping; 3) takeover of RNA-catalyzed aminoacylation by enzymes will necessarily degrade specificity; and 4) the Central Dogma's emergence is most probable when replication and translation error rates remain comparable. These characteristics are necessary and sufficient for the essentially de novo emergence of a coupled gene-replicase-translatase system of genetic coding that would have continuously preserved the functional meaning of genetically encoded protein genes whose phylogenetic relationships match those observed today.}, } @article {pmid29077904, year = {2018}, author = {Hoang, DT and Chernomor, O and von Haeseler, A and Minh, BQ and Vinh, LS}, title = {UFBoot2: Improving the Ultrafast Bootstrap Approximation.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {518-522}, pmid = {29077904}, issn = {1537-1719}, abstract = {The standard bootstrap (SBS), despite being computationally intensive, is widely used in maximum likelihood phylogenetic analyses. We recently proposed the ultrafast bootstrap approximation (UFBoot) to reduce computing time while achieving more unbiased branch supports than SBS under mild model violations. UFBoot has been steadily adopted as an efficient alternative to SBS and other bootstrap approaches. Here, we present UFBoot2, which substantially accelerates UFBoot and reduces the risk of overestimating branch supports due to polytomies or severe model violations. Additionally, UFBoot2 provides suitable bootstrap resampling strategies for phylogenomic data. UFBoot2 is 778 times (median) faster than SBS and 8.4 times (median) faster than RAxML rapid bootstrap on tested data sets. UFBoot2 is implemented in the IQ-TREE software package version 1.6 and freely available at http://www.iqtree.org.}, } @article {pmid29076633, year = {2018}, author = {Masuda, T and Bernát, G and Bečková, M and Kotabová, E and Lawrenz, E and Lukeš, M and Komenda, J and Prášil, O}, title = {Diel regulation of photosynthetic activity in the oceanic unicellular diazotrophic cyanobacterium Crocosphaera watsonii WH8501.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {546-560}, doi = {10.1111/1462-2920.13963}, pmid = {29076633}, issn = {1462-2920}, abstract = {The oceanic unicellular diazotrophic cyanobacterium Crocosphaera watsonii WH8501 exhibits large diel changes in abundance of both Photosystem II (PSII) and Photosystem I (PSI). To understand the mechanisms underlying these dynamics, we assessed photosynthetic parameters, photosystem abundance and composition, and chlorophyll-protein biosynthesis over a diel cycle. Our data show that the decline in PSII activity and abundance observed during the dark period was related to a light-induced modification of PSII, which, in combination with the suppressed synthesis of membrane proteins, resulted in monomerization and gradual disassembly of a large portion of PSII core complexes. In the remaining population of assembled PSII monomeric complexes, we detected the non-functional version of the D1 protein, rD1, which was absent in PSII during the light phase. During the dark period, we also observed a significant decoupling of phycobilisomes from PSII and a decline in the chlorophyll a quota, which matched the complete loss of functional PSIIs and a substantial decrease in PSI abundance. However, the remaining PSI complexes maintained their photochemical activity. Thus, during the nocturnal period of nitrogen fixation C. watsonii operates a suite of regulatory mechanisms for efficient utilization/recycling of cellular resources and protection of the nitrogenase enzyme.}, } @article {pmid29076626, year = {2018}, author = {Wirebrand, L and Madhushani, AWK and Irie, Y and Shingler, V}, title = {Multiple Hfq-Crc target sites are required to impose catabolite repression on (methyl)phenol metabolism in Pseudomonas putida CF600.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {186-199}, doi = {10.1111/1462-2920.13966}, pmid = {29076626}, issn = {1462-2920}, abstract = {The dmp-system encoded on the IncP-2 pVI150 plasmid of Pseudomonas putida CF600 confers the ability to assimilate (methyl)phenols. Regulation of the dmp-genes is subject to sophisticated control, which includes global regulatory input to subvert expression of the pathway in the presence of preferred carbon sources. Previously we have shown that in P. putida, translational inhibition exerted by the carbon repression control protein Crc operates hand-in-hand with the RNA chaperon protein Hfq to reduce translation of the DmpR regulator of the Dmp-pathway. Here, we show that Crc and Hfq co-target four additional sites to form riboprotein complexes within the proximity of the translational initiation sites of genes encoding the first two steps of the Dmp-pathway to mediate two-layered control in the face of selection of preferred substrates. Furthermore, we present evidence that Crc plays a hitherto unsuspected role in maintaining the pVI150 plasmid within a bacterial population, which has implications for (methyl)phenol degradation and a wide variety of other physiological processes encoded by the IncP-2 group of Pseudomonas-specific mega-plasmids.}, } @article {pmid29076622, year = {2018}, author = {Praet, J and Parmentier, A and Schmid-Hempel, R and Meeus, I and Smagghe, G and Vandamme, P}, title = {Large-scale cultivation of the bumblebee gut microbiota reveals an underestimated bacterial species diversity capable of pathogen inhibition.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {214-227}, doi = {10.1111/1462-2920.13973}, pmid = {29076622}, issn = {1462-2920}, abstract = {A total of 1940 isolates from gut samples of 60 bumblebees representing Bombus pascuorum, Bombus terrestris, Bombus lucorum and Bombus lapidarius was collected and identified through state-of the-art taxonomic methods. The bacterial species diversity in these Bombus species exceeded that suggested by phylotype analysis through 16S rRNA amplicon sequencing, and revealed that B. pascuorum and B. terrestris had a unique microbiota composition, each. Representatives of most phylotypes reported earlier and detected in the present study were effectively isolated, and included several novel bacterial taxa and species reported for the first time in the bumblebee gut. Isolates were screened in pectin degradation assays and growth inhibition assays against the honeybee pathogens Paenibacillus larvae, Melissococcus plutonius and Ascosphaera apis and the bumblebee parasite Crithidia bombi. While inhibitory activity against each of these pathogens was observed, only one single culture was able to degrade pectin and polygalacturonic acid in vitro. The availability of accurately identified microbial isolates will facilitate future evaluation of the functional potential of the bumblebee gut microbiota.}, } @article {pmid29076618, year = {2018}, author = {Sulzenbacher, G and Roig-Zamboni, V and Lebrun, R and Guérardel, Y and Murat, D and Mansuelle, P and Yamakawa, N and Qian, XX and Vincentelli, R and Bourne, Y and Wu, LF and Alberto, F}, title = {Glycosylate and move! The glycosyltransferase Maf is involved in bacterial flagella formation.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {228-240}, doi = {10.1111/1462-2920.13975}, pmid = {29076618}, issn = {1462-2920}, abstract = {The flagella of various Gram-negative bacteria are decorated with diverse glycan structures, amongst them nonulosonic acids related to the sialic acid family. Although nonulosonic sugar biosynthesis pathways have been dissected in various pathogens, the enzymes transferring the sugars onto flagellin are still poorly characterized. The deletion of genes coding for motility associated factors (Mafs) found in many pathogenic strains systematically gives rise to nonflagellated bacteria lacking specific nonulosonic sugars on the flagellins, therefore, relating Maf function to flagellin glycosylation and bacterial motility. We investigated the role of Maf from our model organism, Magnetospirillum magneticum AMB-1, in the glycosylation and formation of the flagellum. Deletion of the gene amb0685 coding for Maf produced a nonflagellated bacterium where the flagellin was still produced but no longer glycosylated. Our X-ray structure analysis revealed that the central domain of Maf exhibits similarity to sialyltransferases from Campylobacter jejuni. Glycan analysis suggested that the nonulosonic carbohydrate structure transferred is pseudaminic acid or a very close derivative. This work describes the importance of glycosylation in the formation of the bacterial flagellum and provides the first structural model for a member of a new bacterial glycosyltransferase family involved in nonulosonic acids transfer onto flagellins.}, } @article {pmid29076601, year = {2018}, author = {Shang, JL and Zhang, ZC and Yin, XY and Chen, M and Hao, FH and Wang, K and Feng, JL and Xu, HF and Yin, YC and Tang, HR and Qiu, BS}, title = {UV-B induced biosynthesis of a novel sunscreen compound in solar radiation and desiccation tolerant cyanobacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {200-213}, doi = {10.1111/1462-2920.13972}, pmid = {29076601}, issn = {1462-2920}, abstract = {The small-molecule sunscreen compounds, mycosporine-like amino acids (MAAs), have strong ultraviolet (UV) absorption and can protect cyanobacteria against UV-B damage. However, the molecular mechanism underlying UV-B signaling and MAA chemical diversity remain largely unclear. Here, we identified a five-gene cluster for MAA biosynthesis in the solar radiation and desiccation tolerant cyanobacterium Nostoc flagelliforme. A LuxR family protein OrrA was identified as a positive UV-B responsive regulator binding to the promoter region of this gene cluster. OrrA functions as an activator mediating the UV-B induced MAA biosynthesis. Overexpression of orrA strengthened its UV-B tolerance during desiccation, and enhanced the photosynthetic recovery upon rehydration. Heterologous expression of this gene cluster in Anabaena PCC 7120 produces the same MAA as that in field samples of N. flagelliforme. The MAA structure is assigned as mycosporine-2-(4-deoxygadusolyl-ornithine) with a molecular weight of 756 Da, the structurally unique MAA compound reported to date. This MAA was catalyzed by mysD-mysC2-mysC1 encoding proteins from 4-deoxygadusol, which was synthesized through the catalysis of mysA-mysB products. Thus, we elucidated the transcriptional mechanism for a novel type MAA biosynthesis in solar radiation and desiccation tolerant cyanobacteria, which shed light on the identification of other components for UV-B signaling in cyanobacteria.}, } @article {pmid29075838, year = {2018}, author = {Du, YH and Zhao, YJ and Tang, FH}, title = {A New Molecular Approach Based on the Secondary Structure of Ribosomal RNA for Phylogenetic Analysis of Mobilid Ciliates.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {296-304}, pmid = {29075838}, issn = {1432-0991}, mesh = {DNA, Protozoan/*chemistry/genetics ; Nucleic Acid Conformation ; Oligohymenophorea/chemistry/classification/genetics/*isolation & purification ; *Phylogeny ; RNA, Ribosomal/*chemistry/genetics ; }, abstract = {We analyzed the secondary structure of the small subunit (SSU) rRNA genes of Mobilida (Ciliophora, Peritrichia) and found that the secondary structures of some regions within the SSU-rRNA gene are distinct between the families Trichodinidae and Urceolariidae. Therefore, some of these important regions including H10, H11, H17, H47, H29, H30, H37, E10-1, H45-H46, and V4 (E23-4, E23-7) could be used as the barcodes for classification of these two families. In contrast, V4 (E23-1, E23-2) belongs to a hypervariable region and is not a good barcode at the genus level because of its great inter-specific variation. Our results indicated that the comprehensive analysis of the secondary structure of SSU-rRNA genes is a reliable auxiliary approach for phylogenic study of mobilid ciliates. It was further found that the coevolution between hosts or habitats and the Mobilida ciliates was existent, because the host types and their habitats were critical ecological factors that influenced the evolution of Mobilida ciliates.}, } @article {pmid29074461, year = {2018}, author = {Klimov, PB and OConnor, BM and Chetverikov, PE and Bolton, SJ and Pepato, AR and Mortazavi, AL and Tolstikov, AV and Bauchan, GR and Ochoa, R}, title = {Comprehensive phylogeny of acariform mites (Acariformes) provides insights on the origin of the four-legged mites (Eriophyoidea), a long branch.}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {105-117}, doi = {10.1016/j.ympev.2017.10.017}, pmid = {29074461}, issn = {1095-9513}, mesh = {Animals ; Likelihood Functions ; Mites/*classification ; Models, Biological ; *Phylogeny ; Probability ; }, abstract = {Eriophyoid, or four-legged mites, represent a large and ancient radiation of exclusively phytophagous organisms known from the Triassic (230 Mya). Hypothesizing phylogenetic relatedness of Eriophyoidea among mites is a major challenge due to the absence of unambiguous morphological synapomorphies, resulting in ten published hypotheses placing eriophyoids in various places in the acariform tree of life. Here we test the evolutionary relationships of eriophyoids using six genes and a representative taxonomic sampling of acariform mites. The total evidence analysis places eriophyoids as the sister group of the deep soil-dwelling, vermiform family Nematalycidae (Endeostigmata). This arrangement was supported by the rDNA and CO1 partitions. In contrast, the nuclear protein partition (genes EF1-α, SRP54, HSP70) suggests that Eriophyoidea is sister to a lineage including Tydeidae, Ereynetidae, and Eupodidae (Eupodina: Trombidiformes). On both of these alternative topologies, eriophyoids appear as a long branch, probably involving the loss of basal diversity in early evolution. We analyze this result by using phylogenetically explicit hypothesis testing, investigating the phylogenetic signal from individual genes and rDNA stem and loop regions, and removing long branches and rogue taxa. Regardless of the two alternative placements, (i) the cheliceral morphology of eriophyoids, one of the traits deemed phylogenetically important, was likely derived directly from the plesiomorphic acariform chelicerae rather than from the modified chelicerae of some trombidiform lineages with a reduced fixed digit; and (ii) two potential synapomorphies of Eriophyoidea+Raphignathina (Trombidiformes) related to the reduction of genital papillae and to the terminal position of PS segment can be dismissed as result of convergent evolution. Our analyses substantially narrow the remaining available hypotheses on eriophyoid relationships and provide insights on the early evolution of acariform mites.}, } @article {pmid29074460, year = {2018}, author = {Smith, CH and Johnson, NA and Pfeiffer, JM and Gangloff, MM}, title = {Molecular and morphological data reveal non-monophyly and speciation in imperiled freshwater mussels (Anodontoides and Strophitus).}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {50-62}, doi = {10.1016/j.ympev.2017.10.018}, pmid = {29074460}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Bivalvia/*anatomy & histology/*genetics ; Florida ; *Fresh Water ; *Genetic Speciation ; Geography ; Haplotypes/genetics ; Louisiana ; Mitochondria/metabolism ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Accurate taxonomic placement is vital to conservation efforts considering many intrinsic biological characteristics of understudied species are inferred from closely related taxa. The rayed creekshell, Anodontoides radiatus (Conrad, 1834), exists in the Gulf of Mexico drainages from western Florida to Louisiana and has been petitioned for listing under the Endangered Species Act. We set out to resolve the evolutionary history of A. radiatus, primarily generic placement and species boundaries, using phylogenetic, morphometric, and geographic information. Our molecular matrix contained 3 loci: cytochrome c oxidase subunit I, NADH dehydrogenase subunit I, and the nuclear-encoded ribosomal internal transcribed spacer I. We employed maximum likelihood and Bayesian inference to estimate a phylogeny and test the monophyly of Anodontoides and Strophitus. We implemented two coalescent-based species delimitation models to test seven species models and evaluate species boundaries within A. radiatus. Concomitant to molecular data, we also employed linear morphometrics and geographic information to further evaluate species boundaries. Molecular and morphological evidence supports the inclusion of A. radiatus in the genus Strophitus, and we resurrect the binomial Strophitus radiatus to reflect their shared common ancestry. We also found strong support for polyphyly in Strophitus and advocate the resurrection of the genus Pseudodontoideus to represent 'Strophitus' connasaugaensis and 'Strophitus' subvexus. Strophitus radiatus exists in six well-supported clades that were distinguished as evolutionary independent lineages using Bayesian inference, maximum likelihood, and coalescent-based species delimitation models. Our integrative approach found evidence for as many as 4 evolutionary divergent clades within S. radiatus. Therefore, we formally describe two new species from the S. radiatus species complex (Strophitus williamsi and Strophitus pascagoulaensis) and recognize the potential for a third putative species (Strophitus sp. cf. pascagoulaensis). Our findings aid stakeholders in establishing conservation and management strategies for the members of Anodontoides, Strophitus, and Pseudodontoideus.}, } @article {pmid29071433, year = {2018}, author = {Zhang, H and Chen, M}, title = {Comparison of Different Methods to Identify tdh-Positive Pathogenic Vibrio parahaemolyticus Isolates.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {1-5}, pmid = {29071433}, issn = {1432-0991}, support = {15ZR1435000//Shanghai Municipal Natural Science Foundation/ ; GWTD2015S01//The 4th Three-year Action Plan for Public Health of Shanghai/ ; }, mesh = {Bacterial Proteins/genetics/immunology ; Chromatography, Affinity/*methods ; Food Contamination/analysis ; Humans ; Polymerase Chain Reaction/*methods ; Seafood/*analysis ; Seawater/microbiology ; Vibrio Infections/*microbiology ; Vibrio parahaemolyticus/classification/genetics/immunology/*isolation & purification ; }, abstract = {We evaluated the accuracy and ease of operation of three methods to identify tdh-positive Vibrio parahaemolyticus isolates, including the Kanagawa phenomenon test (KP test), a tdh gene PCR test, and a colloidal gold immunochromatographic assay (CGIA). A total of 221 V. parahaemolyticus isolates were collected from patients, freshly harvested seafood, and fresh seawater. Using the KP test, 92% of V. parahaemolyticus isolates from patients were identified tdh-positive, including four weak KP-positive isolates. The PCR test and CGIA also identified 92% of the isolates as tdh-positive. However, PCR and CGIA only confirmed one of the four weak KP-positive isolates. Similar results were obtained using the three methods to identify V. parahaemolyticus isolates from the other sources. Among the three methods, the KP test was the simplest to perform because it lacked any requirement for sample pretreatment, and was low cost, with no equipment requirements. Therefore, the KP test has been applied widely in many first-line quarantine laboratories. However, the sensitivity and accuracy of KP test were lower than those of the other two methods. PCR can identify the tdh rapidly, specifically, and sensitively. However, PCR requires equipment and facilities that are unavailable in first-line quarantine laboratories. The CGIA can compensate for the disadvantages of the other two methods by its higher sensitivity, accuracy, and ease of operation. Therefore, the CGIA has the highest potential to be used to identify tdh-positive V. parahaemolyticus isolates to guarantee food safety.}, } @article {pmid29069493, year = {2018}, author = {Gao, D and Chu, Y and Xia, H and Xu, C and Heyduk, K and Abernathy, B and Ozias-Akins, P and Leebens-Mack, JH and Jackson, SA}, title = {Horizontal Transfer of Non-LTR Retrotransposons from Arthropods to Flowering Plants.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {354-364}, pmid = {29069493}, issn = {1537-1719}, abstract = {Even though lateral movements of transposons across families and even phyla within multicellular eukaryotic kingdoms have been found, little is known about transposon transfer between the kingdoms Animalia and Plantae. We discovered a novel non-LTR retrotransposon, AdLINE3, in a wild peanut species. Sequence comparisons and phylogenetic analyses indicated that AdLINE3 is a member of the RTE clade, originally identified in a nematode and rarely reported in plants. We identified RTE elements in 82 plants, spanning angiosperms to algae, including recently active elements in some flowering plants. RTE elements in flowering plants were likely derived from a single family we refer to as An-RTE. Interestingly, An-RTEs show significant DNA sequence identity with non-LTR retroelements from 42 animals belonging to four phyla. Moreover, the sequence identity of RTEs between two arthropods and two plants was higher than that of homologous genes. Phylogenetic and evolutionary analyses of RTEs from both animals and plants suggest that the An-RTE family was likely transferred horizontally into angiosperms from an ancient aphid(s) or ancestral arthropod(s). Notably, some An-RTEs were recruited as coding sequences of functional genes participating in metabolic or other biochemical processes in plants. This is the first potential example of horizontal transfer of transposons between animals and flowering plants. Our findings help to understand exchanges of genetic material between the kingdom Animalia and Plantae and suggest arthropods likely impacted on plant genome evolution.}, } @article {pmid29069482, year = {2018}, author = {Gerwien, F and Skrahina, V and Kasper, L and Hube, B and Brunke, S}, title = {Metals in fungal virulence.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {1}, pages = {}, pmid = {29069482}, issn = {1574-6976}, mesh = {Fungi/*chemistry/*pathogenicity ; Homeostasis ; Metals/*metabolism ; *Virulence ; }, abstract = {Metals are essential for life, and they play a central role in the struggle between infecting microbes and their hosts. In fact, an important aspect of microbial pathogenesis is the 'nutritional immunity', in which metals are actively restricted (or, in an extended definition of the term, locally enriched) by the host to hinder microbial growth and virulence. Consequently, fungi have evolved often complex regulatory networks, uptake and detoxification systems for essential metals such as iron, zinc, copper, nickel and manganese. These systems often differ fundamentally from their bacterial counterparts, but even within the fungal pathogens we can find common and unique solutions to maintain metal homeostasis. Thus, we here compare the common and species-specific mechanisms used for different metals among different fungal species-focusing on important human pathogens such as Candida albicans, Aspergillus fumigatus or Cryptococcus neoformans, but also looking at model fungi such as Saccharomyces cerevisiae or A. nidulans as well-studied examples for the underlying principles. These direct comparisons of our current knowledge reveal that we have a good understanding how model fungal pathogens take up iron or zinc, but that much is still to learn about other metals and specific adaptations of individual species-not the least to exploit this knowledge for new antifungal strategies.}, } @article {pmid29069452, year = {2018}, author = {Kosheleva, K and Desai, MM}, title = {Recombination Alters the Dynamics of Adaptation on Standing Variation in Laboratory Yeast Populations.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {180-201}, pmid = {29069452}, issn = {1537-1719}, support = {R01 GM104239/GM/NIGMS NIH HHS/United States ; }, abstract = {The rates and selective effects of beneficial mutations, together with population genetic factors such as population size and recombination rate, determine the outcomes of adaptation and the signatures this process leaves in patterns of genetic diversity. Previous experimental studies of microbial evolution have focused primarily on initially clonal populations, finding that adaptation is characterized by new strongly selected beneficial mutations that sweep rapidly to fixation. Here, we study evolution in diverse outcrossed yeast populations, tracking the rate and genetic basis of adaptation over time. We combine time-serial measurements of fitness and allele frequency changes in 18 populations of budding yeast evolved at different outcrossing rates to infer the drivers of adaptation on standing genetic variation. In contrast to initially clonal populations, we find that adaptation is driven by a large number of weakly selected, linked variants. Populations undergoing different rates of outcrossing make use of this selected variation differently: whereas asexual populations evolve via rapid, inefficient, and highly variable fixation of clones, sexual populations adapt continuously by gradually breaking down linkage disequilibrium between selected variants. Our results demonstrate how recombination can sustain adaptation over long timescales by inducing a transition from selection on genotypes to selection on individual alleles, and show how pervasive linked selection can affect evolutionary dynamics.}, } @article {pmid29069429, year = {2018}, author = {Peng, F and Widmann, S and Wünsche, A and Duan, K and Donovan, KA and Dobson, RCJ and Lenski, RE and Cooper, TF}, title = {Effects of Beneficial Mutations in pykF Gene Vary over Time and across Replicate Populations in a Long-Term Experiment with Bacteria.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {202-210}, pmid = {29069429}, issn = {1537-1719}, abstract = {The fitness effects of mutations can depend on the genetic backgrounds in which they occur and thereby influence future opportunities for evolving populations. In particular, mutations that fix in a population might change the selective benefit of subsequent mutations, giving rise to historical contingency. We examine these effects by focusing on mutations in a key metabolic gene, pykF, that arose independently early in the history of 12 Escherichia coli populations during a long-term evolution experiment. Eight different evolved nonsynonymous mutations conferred similar fitness benefits of ∼10% when transferred into the ancestor, and these benefits were greater than the one conferred by a deletion mutation. In contrast, the same mutations had highly variable fitness effects, ranging from ∼0% to 25%, in evolved clones isolated from the populations at 20,000 generations. Two mutations that were moved into these evolved clones conferred similar fitness effects in a given clone, but different effects between the clones, indicating epistatic interactions between the evolved pykF alleles and the other mutations that had accumulated in each evolved clone. We also measured the fitness effects of six evolved pykF alleles in the same populations in which they had fixed, but at seven time points between 0 and 50,000 generations. Variation in fitness effects was high at intermediate time points, and declined to a low level at 50,000 generations, when the mean fitness effect was lowest. Our results demonstrate the importance of genetic context in determining the fitness effects of different beneficial mutations even within the same gene.}, } @article {pmid29069427, year = {2018}, author = {Klobucar, K and Brown, ED}, title = {Use of genetic and chemical synthetic lethality as probes of complexity in bacterial cell systems.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {1}, pages = {}, doi = {10.1093/femsre/fux054}, pmid = {29069427}, issn = {1574-6976}, support = {FRN-143215//CIHR/Canada ; }, mesh = {Anti-Bacterial Agents/pharmacology ; Bacteria/drug effects/*genetics ; Drug Discovery/*methods ; Drug Synergism ; Genome, Bacterial/genetics ; *Genomics ; *Synthetic Lethal Mutations ; }, abstract = {Different conditions and genomic contexts are known to have an impact on gene essentiality and interactions. Synthetic lethal interactions occur when a combination of perturbations, either genetic or chemical, result in a more profound fitness defect than expected based on the effect of each perturbation alone. Synthetic lethality in bacterial systems has long been studied; however, during the past decade, the emerging fields of genomics and chemical genomics have led to an increase in the scale and throughput of these studies. Here, we review the concepts of genomics and chemical genomics in the context of synthetic lethality and their revolutionary roles in uncovering novel biology such as the characterization of genes of unknown function and in antibacterial drug discovery. We provide an overview of the methodologies, examples and challenges of both genetic and chemical synthetic lethal screening platforms. Finally, we discuss how to apply genetic and chemical synthetic lethal approaches to rationalize the synergies of drugs, screen for new and improved antibacterial therapies and predict drug mechanism of action.}, } @article {pmid29069410, year = {2018}, author = {Heinisch, JJ and Rodicio, R}, title = {Protein kinase C in fungi-more than just cell wall integrity.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {1}, pages = {}, doi = {10.1093/femsre/fux051}, pmid = {29069410}, issn = {1574-6976}, mesh = {Antifungal Agents/chemistry/pharmacology ; Cell Wall/drug effects/enzymology ; *Drug Delivery Systems ; Enzyme Activation/drug effects ; Humans ; Mycoses/drug therapy ; Protein Kinase C/*metabolism ; Saccharomyces cerevisiae/*enzymology/genetics ; Saccharomyces cerevisiae Proteins/*metabolism ; }, abstract = {Human protein kinase C (PKC) isoforms have been implicated in diseases such as Alzheimer's, diabetes and cancers. In contrast to mammals, which have at least nine genes, fungi have only one or two. The yeast Saccharomyces cerevisiae produces only a single Pkc1 and is employed in the study of specific human isozymes, including their susceptibility to pharmacological drugs. Vice versa, the domain structure and regulation of yeast and other fungal PKCs yield insights into the function of human isozymes. Therefore, human PKCs are briefly reviewed herein and related to the yeast enzyme. The latter was originally implicated in the regulation of cell wall synthesis through a conserved MAP kinase pathway, but many more targets have now been described in S. cerevisiae and other fungi. These implicate PKC in the control of such diverse processes as the organization of the actin cytoskeleton, autophagy and apoptosis, nutrient sensing and ribosome biogenesis, cell cycle control, cytokinesis and genetic stability. PKC is a promising target for the development of antifungal drugs against pathogenic fungi such as Candida albicans, Cryptococcus neoformans and Aspergillus fumigatus. Thus, fungal PKCs are drawing increased attention and the accumulating literature on the enzymes from different species is summarized herein.}, } @article {pmid29069389, year = {2018}, author = {Ariani, A and Berny Mier Y Teran, JC and Gepts, P}, title = {Spatial and Temporal Scales of Range Expansion in Wild Phaseolus vulgaris.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {119-131}, pmid = {29069389}, issn = {1537-1719}, support = {S10 RR027303/RR/NCRR NIH HHS/United States ; S10 RR029668/RR/NCRR NIH HHS/United States ; }, abstract = {The wild progenitor of common-bean has an exceptionally large distribution from northern Mexico to northwestern Argentina, unusual among crop wild progenitors. This research sought to document major events of range expansion that led to this distribution and associated environmental changes. Through the use of genotyping-by-sequencing (∼20,000 SNPs) and geographic information systems applied to a sample of 246 accessions of wild Phaseolus vulgaris, including 157 genotypes of the Mesoamerican, 77 of the southern Andean, and 12 of the Northern Peru-Ecuador gene pools, we identified five geographically distinct subpopulations. Three of these subpopulations belong to the Mesoamerican gene pool (Northern and Central Mexico, Oaxaca, and Southern Mexico, Central America and northern South America) and one each to the Northern Peru-Ecuador (PhI) and the southern Andean gene pools. The five subpopulations were distributed in different floristic provinces of the Neotropical seasonally dry forest and showed distinct distributions for temperature and rainfall resulting in decreased local potential evapotranspiration (PhI and southern Andes groups) compared with the two Mexican groups. Three of these subpopulations represent long-distance dispersal events from Mesoamerica into Northern Peru-Ecuador, southern Andes, and Central America and Colombia, in chronological order. Of particular note is that the dispersal to Northern Peru-Ecuador markedly predates the dispersal to the southern Andes (∼400 vs. ∼100 ky), consistent with the ancestral nature of the phaseolin seed protein and chloroplast sequences observed in the PhI group. Seed dispersal in common bean can be, therefore, described at different spatial and temporal scales, from localized, annual seed shattering to long-distance, evolutionarily rare migration.}, } @article {pmid29069382, year = {2018}, author = {Bengtsson-Palme, J and Kristiansson, E and Larsson, DGJ}, title = {Environmental factors influencing the development and spread of antibiotic resistance.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {1}, pages = {}, pmid = {29069382}, issn = {1574-6976}, mesh = {Bacterial Physiological Phenomena/*genetics ; Drug Resistance, Microbial/*genetics ; *Environment ; *Evolution, Molecular ; }, abstract = {Antibiotic resistance and its wider implications present us with a growing healthcare crisis. Recent research points to the environment as an important component for the transmission of resistant bacteria and in the emergence of resistant pathogens. However, a deeper understanding of the evolutionary and ecological processes that lead to clinical appearance of resistance genes is still lacking, as is knowledge of environmental dispersal barriers. This calls for better models of how resistance genes evolve, are mobilized, transferred and disseminated in the environment. Here, we attempt to define the ecological and evolutionary environmental factors that contribute to resistance development and transmission. Although mobilization of resistance genes likely occurs continuously, the great majority of such genetic events do not lead to the establishment of novel resistance factors in bacterial populations, unless there is a selection pressure for maintaining them or their fitness costs are negligible. To enable preventative measures it is therefore critical to investigate under what conditions and to what extent environmental selection for resistance takes place. In addition, understanding dispersal barriers is not only key to evaluate risks, but also to prevent resistant pathogens, as well as novel resistance genes, from reaching humans.}, } @article {pmid29069367, year = {2018}, author = {Matilla, MA and Krell, T}, title = {The effect of bacterial chemotaxis on host infection and pathogenicity.}, journal = {FEMS microbiology reviews}, volume = {42}, number = {1}, pages = {}, doi = {10.1093/femsre/fux052}, pmid = {29069367}, issn = {1574-6976}, mesh = {Animals ; Bacteria/*pathogenicity ; Bacterial Physiological Phenomena ; Bacterial Proteins/metabolism ; *Chemotaxis ; Host-Pathogen Interactions/*physiology ; Humans ; Plants/microbiology ; *Signal Transduction ; }, abstract = {Chemotaxis enables microorganisms to move according to chemical gradients. Although this process requires substantial cellular energy, it also affords key physiological benefits, including enhanced access to growth substrates. Another important implication of chemotaxis is that it also plays an important role in infection and disease, as chemotaxis signalling pathways are broadly distributed across a variety of pathogenic bacteria. Furthermore, current research indicates that chemotaxis is essential for the initial stages of infection in different human, animal and plant pathogens. This review focuses on recent findings that have identified specific bacterial chemoreceptors and corresponding chemoeffectors associated with pathogenicity. Pathogenicity-related chemoeffectors are either host and niche-specific signals or intermediates of the host general metabolism. Plant pathogens were found to contain an elevated number of chemotaxis signalling genes and functional studies demonstrate that these genes are critical for their ability to enter the host. The expanding body of knowledge of the mechanisms underlying chemotaxis in pathogens provides a foundation for the development of new therapeutic strategies capable of blocking infection and preventing disease by interfering with chemotactic signalling pathways.}, } @article {pmid29068277, year = {2018}, author = {Shin, SK and Kim, E and Yi, H}, title = {Paenibacillus crassostreae sp. nov., isolated from the Pacific oyster Crassostrea gigas.}, journal = {International journal of systematic and evolutionary microbiology}, volume = {68}, number = {1}, pages = {58-63}, doi = {10.1099/ijsem.0.002444}, pmid = {29068277}, issn = {1466-5034}, mesh = {Animals ; Bacterial Typing Techniques ; Base Composition ; Crassostrea/*microbiology ; DNA, Bacterial/genetics ; Diaminopimelic Acid/chemistry ; Fatty Acids/chemistry ; Nucleic Acid Hybridization ; Paenibacillus/*classification/genetics/isolation & purification ; Peptidoglycan/chemistry ; Phospholipids/chemistry ; *Phylogeny ; RNA, Ribosomal, 16S/genetics ; Republic of Korea ; Sequence Analysis, DNA ; Vitamin K 2/analogs & derivatives/chemistry ; }, abstract = {A Gram-stain-positive, endospore-forming, rod-shaped, aerobic bacterium, designated LPB0068T, was isolated from a Pacific oyster (Crassostrea gigas) in Korea. This isolate was found to share the highest 16S rRNA gene sequence similarity with Paenibacillus macquariensis subsp. macquariensis DSM 2T (98.1 %) and Paenibacillus macquariensis subsp. defensor JCM 14954T (98.0 %). To establish the genomic relatedness of this isolate to its phylogenetic neighbours, its genome sequence and those of Paenibacillus antarcticus CECT 5836T, P. macquariensis subsp. macquariensis DSM 2T, P. macquariensis subsp. defensor JCM 14954T, and Paenibacillus glacialis DSM 22343T were determined. The low average nucleotide identity and digital DNA-DNA hybridization values exhibited by LPB0068T in relation to the other strains in this analysis revealed that it is distinct from other Paenibacillus species. The genome of strain LPB0068T consists of one chromosome and three circular plasmids, and had a DNA G+C content of 40.0 mol%. The major respiratory quinone was menaquinone-7 and the diagnostic diamino acid in the cell-wall peptidoglycan was meso-diaminopimelic acid. The major polar lipids consisted of phosphatidylglycerol, diphosphatidylglycerol, phosphatidylethanolamine, one unidentified phospholipid, one unidentified glycolipid, and two unidentified polar lipids. The major cellular fatty acids were anteiso-C15 : 0, C14 : 0, and C16 : 0. Based on genomic, phylogenetic, and phenotypic characteristics, this strain was clearly distinguished from other Paenibacillus species with validly published names and should therefore be classified as a novel species of the genus. The name Paenibacillus crassostreae sp. nov. is proposed, the type strain of which is LPB0068T (=KACC 18694T=JCM 31183T).}, } @article {pmid29068134, year = {2018}, author = {Chandhok, G and Lazarou, M and Neumann, B}, title = {Structure, function, and regulation of mitofusin-2 in health and disease.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {933-949}, doi = {10.1111/brv.12378}, pmid = {29068134}, issn = {1469-185X}, abstract = {Mitochondria are highly dynamic organelles that constantly migrate, fuse, and divide to regulate their shape, size, number, and bioenergetic function. Mitofusins (Mfn1/2), optic atrophy 1 (OPA1), and dynamin-related protein 1 (Drp1), are key regulators of mitochondrial fusion and fission. Mutations in these molecules are associated with severe neurodegenerative and non-neurological diseases pointing to the importance of functional mitochondrial dynamics in normal cell physiology. In recent years, significant progress has been made in our understanding of mitochondrial dynamics, which has raised interest in defining the physiological roles of key regulators of fusion and fission and led to the identification of additional functions of Mfn2 in mitochondrial metabolism, cell signalling, and apoptosis. In this review, we summarize the current knowledge of the structural and functional properties of Mfn2 as well as its regulation in different tissues, and also discuss the consequences of aberrant Mfn2 expression.}, } @article {pmid29067680, year = {2018}, author = {Moritz, CC and Pratt, RC and Bank, S and Bourke, G and Bragg, JG and Doughty, P and Keogh, JS and Laver, RJ and Potter, S and Teasdale, LC and Tedeschi, LG and Oliver, PM}, title = {Cryptic lineage diversity, body size divergence, and sympatry in a species complex of Australian lizards (Gehyra).}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {54-66}, doi = {10.1111/evo.13380}, pmid = {29067680}, issn = {1558-5646}, abstract = {Understanding the joint evolutionary and ecological underpinnings of sympatry among close relatives remains a key challenge in biology. This problem can be addressed through joint phylogenomic and phenotypic analysis of complexes of closely related lineages within, and across, species and hence representing the speciation continuum. For a complex of tropical geckos from northern Australia-Gehyra nana and close relatives-we combine mtDNA phylogeography, exon-capture sequencing, and morphological data to resolve independently evolving lineages and infer their divergence history and patterns of morphological evolution. Gehyra nana is found to include nine divergent lineages and is paraphyletic with four other species from the Kimberley region of north-west Australia. Across these 13 taxa, 12 of which are restricted to rocky habitats, several lineages overlap geographically, including on the diverse Kimberley islands. Morphological evolution is dominated by body size shifts, and both body size and shape have evolved gradually across the group. However, larger body size shifts are observed among overlapping taxa than among closely related parapatric lineages of G. nana, and sympatric lineages are more divergent than expected at random. Whether elevated body size differences among sympatric lineages are due to ecological sorting or character displacement remains to be determined.}, } @article {pmid29066288, year = {2018}, author = {Kretschmann, J and Žerdoner Čalasan, A and Gottschling, M}, title = {Molecular phylogenetics of dinophytes harboring diatoms as endosymbionts (Kryptoperidiniaceae, Peridiniales), with evolutionary interpretations and a focus on the identity of Durinskia oculata from Prague.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {392-402}, doi = {10.1016/j.ympev.2017.10.011}, pmid = {29066288}, issn = {1095-9513}, mesh = {Czech Republic ; Diatoms/*cytology/genetics ; Likelihood Functions ; Phylogeny ; RNA, Ribosomal/chemistry/genetics ; Sequence Analysis, DNA ; }, abstract = {Peridinialean dinophytes include a unique evolutionary group of algae harboring a diatom as an endosymbiont (Kryptoperidiniaceae), whose phylogenetic origin and internal relationships are not fully resolved at present. Several interpretations of the thecal plate pattern present in Durinskia oculata currently compete and lead to considerable taxonomic confusion. Moreover, it is unclear at present whether the species is restricted to freshwater habitats, or occurs in the marine environment as well. We collected material at the type locality of D. oculata in the Czech Republic and established monoclonal strains. Dinophyte cells were studied using light and electron microscopy, and we also determined DNA sequences of several rRNA regions (including the Internal Transcribed Spacers) for molecular characterization and phylogenetics. The morphology of strain GeoM∗662 indicated a plate formula of Po, X, 4', 2a, 6″, 5c, 5s, 5‴, 2⁗, which was sustained also in form of a microscopic slide serving as an epitype. In the molecular DNA tree based on a matrix composed of concatenated rRNA sequences, strain GeoM∗662 showed a close relationship to other species of Durinskia, and the freshwater species clearly differs from the marine members. Two independent colonization events from the marine into the freshwater environment can be inferred within the Kryptoperidiniaceae. We provide a summarizing cladogram of dinophytes harboring a diatom as endosymbiont with evolutionary novelties indicated as well as a morphological key to the 6 species of Durinskia that are currently accepted.}, } @article {pmid29063971, year = {2018}, author = {Naik, T and Vanitha, SC and Rajvanshi, PK and Chandrika, M and Kamalraj, S and Jayabaskaran, C}, title = {Novel Microbial Sources of Tropane Alkaloids: First Report of Production by Endophytic Fungi Isolated from Datura metel L.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {206-212}, pmid = {29063971}, issn = {1432-0991}, support = {BT/PR14760/NDB/52/188/2010//Department of Biotechnology/ ; }, mesh = {Alcohol Oxidoreductases/genetics ; Ascomycota/classification/genetics/*isolation & purification/*metabolism ; Cluster Analysis ; DNA, Fungal/chemistry/genetics ; DNA, Ribosomal Spacer/chemistry/genetics ; Datura metel/*microbiology ; Endophytes/classification/genetics/*isolation & purification/*metabolism ; Methyltransferases/genetics ; Mixed Function Oxygenases/genetics ; Phylogeny ; Sequence Analysis, DNA ; Tropanes/*metabolism ; }, abstract = {Eighteen endophytic fungi were isolated from various tissues of Datura metel and genes encoding for putrescine N-methyltransferase (PMT), tropinone reductase 1 (TR1) and hyoscyamine 6β-hydroxylase (H6H) were used as molecular markers for PCR-based screening approach for tropane alkaloids (TAs) producing endophytic fungi. These fungi were identified taxonomically by sequence analysis of the internal transcribed spacer region (ITS1-5.8S-ITS2) and also based on morphological characteristics of the fungal spore as Colletotrichum boninense, Phomopsis sp., Fusarium solani, Colletotrichum incarnatum, Colletotrichum siamense and Colletotrichum gloeosporioides. The production of TAs hyoscyamine and scopolamine by the fungi has been ascertained using chromatography and spectroscopy methods by comparison with the standards. Among the fungi, the highest yields of hyoscyamine (3.9 mg/L) and scopolamine (4.1 mg/L) were found in C. incarnatum culture. This is the first report of endophytic fungi possess the PMT, TR1 and H6H genes and produces TAs. These endophytic fungi have significant potential to be applied in fermentation technology to meet the demands for TAs economically.}, } @article {pmid29063970, year = {2018}, author = {Maas, MB and Maybery, GHC and Perold, WJ and Neveling, DP and Dicks, LMT}, title = {Borosilicate Glass Fiber-Optic Biosensor for the Detection of Escherichia coli.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {150-155}, pmid = {29063970}, issn = {1432-0991}, support = {CPRR13090533029//National Research Foundation/ ; }, mesh = {Antibodies, Bacterial/metabolism ; Biosensing Techniques/*instrumentation/*methods ; Escherichia coli/*isolation & purification ; *Glass ; Protein Binding ; Sensitivity and Specificity ; }, abstract = {Polyclonal antibodies against Escherichia coli and fluorescent, secondary, antibodies were immobilized on borosilicate glass fibers pre-treated with 3-glycidyloxypropyl trimethoxysilane (GPS). Light with an average wavelength of 627 nm, emitted by a diode placed at one end of the glass fiber, was detected by an ultrasensitive photodiode with peak sensitivity at 640 nm. Changes in fluorescence, caused by binding of E. coli to the antibodies, changed the net refractive index of the glass fiber and thus the internal reflection of light. These evanescent changes in photon energy were recorded by an ultrasensitive photodiode. Signals were amplified and changes in voltage recorded with a digital multimeter. A linear increase in voltage readings was recorded over 2 h when 3.0 × 107 CFU/ml and 2.77 × 109 CFU/ml E. coli were adhered to the antibodies. Voltage readings were recorded with E. coli cell numbers from 2 × 103 CFU/ml to 2 × 106 CFU/ml, but readings remained unchanged for 2 h, indicating that the limit of detection is 3.0 × 107 CFU/ml. This simple technology may be used to develop a low-cost, portable, fiber-optic biosensor to detect E. coli in infections and may have applications in the medical field. Research is in progress to optimize the sensitivity of the fiber-optic biosensor and determine its specificity.}, } @article {pmid29063969, year = {2018}, author = {Zeng, B and Sun, L and Chen, Y and Qian, Y and Cao, Q and Zhang, Z and Li, Z}, title = {Neisseria flavescens: A Urease-Expressing Potential Pathogen Isolated from Gastritis Patients.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {186-193}, pmid = {29063969}, issn = {1432-0991}, support = {12ZA266//the Sichuan Provincial Education Department Foundation of China/ ; 2015RC30//Natural Science Foundation of Sichuan University of Science and Engineering/ ; 2017RZ0083//the Sichuan Province Science and Technology Support Program/ ; }, mesh = {Biopsy ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Gastritis/*diagnosis/*microbiology ; Humans ; Microbial Sensitivity Tests ; Neisseria/drug effects/enzymology/genetics/*isolation & purification ; Neisseriaceae Infections/*diagnosis/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Urease/*analysis ; }, abstract = {Parasitic pathogens, such as H. pylori (Helicobacter pylori), are considered as primary elements for causing stomach infection and leading to chronic gastritis or ulcers. Here, an unreported urease- and oxidase-producing Neisseria flavescens-like bacteria was isolated from the gastroscopic biopsies of 14C-UBT-positive gastritis patients. The isolate expressed the activity of urease, which is a pathogenic factor and considered as a reliable marker for diagnosis of H. pylori infection. However, the isolate didn't express the key functional genes of H. pylori including vacA and hpaA, and also the morphological feature of isolate was significantly different with H. pylori. Eventually, the 16S rDNA of isolate was sequenced and its sequence shared about 99.8% similarity with the N. flavescens standard strains, but about 20.8% similarity with the H. pylori. Further study of antibiotics-resistance revealed the N. flavescens isolate is high resistant to metronidazole, but highly sensitive to ampicillin sodium. To summarize, a urease-expressing N. flavescens strain was isolated and identified from Chinese gastritis patients; the encouraging results provides an important reference for the further study of its pathogenicity and the reasonable diagnosis and use of antibiotics clinically.}, } @article {pmid29063968, year = {2018}, author = {Yan, DZ and Gan, YT and Zhou, H and Liu, J and Li, X}, title = {Draft Genome Sequence of Cyclohexylamine-Degrading Strain Acinetobacter sp. YT-02 Isolated.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {284-287}, pmid = {29063968}, issn = {1432-0991}, support = {31270112//National Natural Science Foundation Program of China/ ; MMLKF14-06//State Key Laboratory of Microbial Metabolism (Shanghai Jiao Tong University)/ ; }, mesh = {Acinetobacter/classification/*genetics/*isolation & purification/metabolism ; Base Sequence ; Biodegradation, Environmental ; Cyclohexylamines/*metabolism ; DNA, Bacterial/genetics ; *Genome, Bacterial ; Molecular Sequence Data ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sewage/microbiology ; }, abstract = {Acinetobacter sp. YT-02, a Gram-negative bacterium isolated from the activated sludge from a sodium N-cyclohexylsulfamate production plant, has the ability to degrade cyclohexylamine. It was classified as a member of Acinetobacter sp., a Gram-negative bacterium, sharing a 16S rRNA gene sequence identity of 99% with Acinetobacter guangdongensis strain 1NM-4. It could degrade 10 mmol/L cyclohexylamine within 22 h. Based on the identified metabolite, the metabolic pathway of cyclohexylamine could be postulated as it was degraded via cyclohexanone. Draft genome sequence of this strain (2,993, 647 bp of chromosome length) is presented here. We further identified the genes encoding the enzymes involved in cyclohexylamine oxidation to cyclohexanone and the subsequent downstream metabolic pathway of cyclohexanone oxidation. Strain YT-02 has the potentiality to be applied in the treatment of the pollutant cyclohexylamine, and it could also be treated as a research material to study the degradation mechanism of cyclohexylamine.}, } @article {pmid29063967, year = {2018}, author = {Zalewska, B and Kaevska, M and Slana, I}, title = {Sequence Analysis of Changes in Microbial Composition in Different Milk Products During Fermentation and Storage.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {202-205}, pmid = {29063967}, issn = {1432-0991}, support = {LO1218//MEYS of the Czech Republic under the NPU I program/ ; }, mesh = {Animals ; Bacteria/*classification/*genetics ; *Biota ; Cattle ; Cultured Milk Products/*microbiology ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Fermentation ; Food Storage ; Goats ; Milk ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {The objective of this study was to analyze the changes in the microbiota of milk products during fermentation and storage. Two kinds of Yoghurt, one Kefir, and one Acidophilus milk were observed during the fermentation process and storage using 16S rDNA amplicon sequencing. Cow's, goat's, raw and pasteurized milk were also examined. The most represented organisms in all manufactured products were shown to be those of the phylum Firmicutes. In some products, Proteobacteria, Bacteroidetes and Actinobacteria were also present in high amounts.}, } @article {pmid29063966, year = {2018}, author = {Jiang, Y and Chen, T and Dong, W and Zhang, M and Zhang, W and Wu, H and Ma, J and Jiang, M and Xin, F}, title = {The Draft Genome Sequence of Clostridium beijerinckii NJP7, a Unique Bacterium Capable of Producing Isopropanol-Butanol from Hemicellulose Through Consolidated Bioprocessing.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {305-308}, pmid = {29063966}, issn = {1432-0991}, support = {KL16-08//the Project of State Key Laboratory of Materials-Oriented Chemical Engineering/ ; No. 21706125//the National Natural Science Foundation of China/ ; No. 21727818//the National Natural Science Foundation of China/ ; No. 21706124//the National Natural Science Foundation of China/ ; No. 31700092//the National Natural Science Foundation of China/ ; No. BK20170993//Jiangsu Province Natural Science Foundation for Youths/ ; }, mesh = {2-Propanol/*metabolism ; Base Sequence ; Butanols/*metabolism ; China ; Clostridium beijerinckii/classification/*genetics/isolation & purification/*metabolism ; *Genome, Bacterial ; Polysaccharides/*metabolism ; Soil Microbiology ; }, abstract = {A wild type solventogenic Clostridium beijerinckii NJP7 capable of converting polysaccharides, such as hemicellulose, into butanol and isopropanol via a unique acetone-isopropanol-butanol (AIB) pathway was isolated and characterized. This represents the first wild type isopropanol-butanol generating bacterium which could achieve butanol production directly from lignocellulose through consolidated bioprocessing (CBP). Strain NJP7 was isolated from decomposite soil from Laoshan Nature Park, China, and its genome shows 98.6% identical to 89.5% of the Clostridium diolis submitted genome sequence. The assembled draft genome contains 5.76 Mb and 5101 predicted encoding proteins with a GC content of 29.73%. Among these annotated proteins, hemicellulase and the secondary alcohol dehydrogenase play key roles in achievement of AIB production from hemicellulose through CBP.}, } @article {pmid29062088, year = {2018}, author = {Shapiro, RS and Chavez, A and Porter, CBM and Hamblin, M and Kaas, CS and DiCarlo, JE and Zeng, G and Xu, X and Revtovich, AV and Kirienko, NV and Wang, Y and Church, GM and Collins, JJ}, title = {A CRISPR-Cas9-based gene drive platform for genetic interaction analysis in Candida albicans.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {73-82}, pmid = {29062088}, issn = {2058-5276}, support = {RM1 HG008525/HG/NHGRI NIH HHS/United States ; T32 CA009216/CA/NCI NIH HHS/United States ; }, mesh = {Biofilms/growth & development ; *CRISPR-Cas Systems ; Candida albicans/drug effects/*genetics/growth & development ; Fluconazole/pharmacology ; Fungal Proteins/genetics ; Gene Deletion ; *Gene Drive Technology ; Gene Expression Regulation, Fungal/drug effects ; *Genetic Techniques ; High-Throughput Screening Assays ; Homozygote ; Virulence/genetics ; }, abstract = {Candida albicans is the leading cause of fungal infections; yet, complex genetic interaction analysis remains cumbersome in this diploid pathogen. Here, we developed a CRISPR-Cas9-based 'gene drive array' platform to facilitate efficient genetic analysis in C. albicans. In our system, a modified DNA donor molecule acts as a selfish genetic element, replaces the targeted site and propagates to replace additional wild-type loci. Using mating-competent C. albicans haploids, each carrying a different gene drive disabling a gene of interest, we are able to create diploid strains that are homozygous double-deletion mutants. We generate double-gene deletion libraries to demonstrate this technology, targeting antifungal efflux and biofilm adhesion factors. We screen these libraries to identify virulence regulators and determine how genetic networks shift under diverse conditions. This platform transforms our ability to perform genetic interaction analysis in C. albicans and is readily extended to other fungal pathogens.}, } @article {pmid29062087, year = {2018}, author = {Orsi, WD and Richards, TA and Francis, WR}, title = {Predicted microbial secretomes and their target substrates in marine sediment.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {32-37}, doi = {10.1038/s41564-017-0047-9}, pmid = {29062087}, issn = {2058-5276}, mesh = {Archaea/classification/enzymology/*genetics ; Bacteria/classification/enzymology/*genetics ; Carbon Cycle/*genetics ; Fungi/classification/enzymology/*genetics ; Gene Expression Profiling ; Genome, Microbial/genetics ; Geologic Sediments/*microbiology ; Metagenomics ; Open Reading Frames/genetics ; Proteogenomics ; Seawater/*microbiology ; Sequence Analysis, DNA ; }, abstract = {Scientific drilling has identified a biosphere in marine sediments 1 , which contain many uncultivated microbial groups known only by their DNA sequences 2-4 . Recycling of organic matter in sediments is an important component of biogeochemical cycles because marine sediments are critical for long-term carbon storage 5 . Turnover of carbon is hypothesized to be driven by the secretion of enzymes by microbial organisms 5-7 , which act to break down macromolecules into constitutive monomers that can be transported into cells. As such, the nature of the microbial secretome often influences the function of a community 6 . However, the microbial groups involved in this process and the biochemistry they encode is poorly understood. Here, we show that expressed genes from 5 to 159 meters below the seafloor 8 (mbsf) encode numerous candidate peptidases and carbohydrate-active enzymes ('CAZymes') 9 targeted for secretion. The majority (90-99%) were assigned to Bacteria, of which 12% shared the highest sequence similarity with candidate phyla 10,11 . The remaining putatively secreted proteins shared highest sequence similarity with archaeal and fungal enzymes, which peak in two redox transition zones 12 . In the shallower redox zone at 30 mbsf, 20% of the transcripts encoding putative secreted peptidases were assigned to lineages 7,13,14 of uncultivated Archaea. The target compounds of the predicted secreted proteome show a preference for necromass in the form of microbial cell envelopes as well as plankton and algal detritus. The predicted fungal secreted proteome encodes CAZymes not present in the predicted bacterial or archaeal secreted proteomes, indicating that fungi putatively play a minimal but specialized role in subseafloor carbohydrate recycling.}, } @article {pmid29062072, year = {2018}, author = {Lohse, MB and Gulati, M and Johnson, AD and Nobile, CJ}, title = {Development and regulation of single- and multi-species Candida albicans biofilms.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {19-31}, pmid = {29062072}, issn = {1740-1534}, support = {R01 AI083311/AI/NIAID NIH HHS/United States ; R41 AI112038/AI/NIAID NIH HHS/United States ; }, mesh = {Antifungal Agents/pharmacology ; *Biofilms/drug effects/growth & development ; Candida albicans/classification/drug effects/*physiology ; Drug Resistance, Fungal ; Gene Expression Regulation, Fungal/drug effects ; Gene Regulatory Networks ; Humans ; }, abstract = {Candida albicans is among the most prevalent fungal species of the human microbiota and asymptomatically colonizes healthy individuals. However, it is also an opportunistic pathogen that can cause severe, and often fatal, bloodstream infections. The medical impact of C. albicans typically depends on its ability to form biofilms, which are closely packed communities of cells that attach to surfaces, such as tissues and implanted medical devices. In this Review, we provide an overview of the processes involved in the formation of C. albicans biofilms and discuss the core transcriptional network that regulates biofilm development. We also consider some of the advantages that biofilms provide to C. albicans in comparison with planktonic growth and explore polymicrobial biofilms that are formed by C. albicans and certain bacterial species.}, } @article {pmid29062071, year = {2018}, author = {Pawluk, A and Davidson, AR and Maxwell, KL}, title = {Anti-CRISPR: discovery, mechanism and function.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {12-17}, pmid = {29062071}, issn = {1740-1534}, mesh = {Bacteria/*virology ; *Bacterial Physiological Phenomena ; Bacteriophages/*physiology ; Biological Evolution ; Biotechnology ; *CRISPR-Cas Systems ; *Clustered Regularly Interspaced Short Palindromic Repeats ; Evolution, Molecular ; Host-Pathogen Interactions/*genetics/immunology ; Protein Binding ; Viral Proteins/genetics/metabolism ; }, abstract = {CRISPR-Cas adaptive immune systems are widespread among bacteria and archaea. Recent studies have shown that these systems have minimal long-term evolutionary effects in limiting horizontal gene transfer. This suggests that the ability to evade CRISPR-Cas immunity must also be widespread in phages and other mobile genetic elements. In this Progress article, we discuss recent discoveries that highlight how phages inactivate CRISPR-Cas systems by using anti-CRISPR proteins, and we outline evolutionary and biotechnological implications of their activity.}, } @article {pmid29062070, year = {2018}, author = {Cookson, WOCM and Cox, MJ and Moffatt, MF}, title = {New opportunities for managing acute and chronic lung infections.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {2}, pages = {111-120}, pmid = {29062070}, issn = {1740-1534}, support = {G1000758//Medical Research Council/United Kingdom ; }, abstract = {Lung diseases caused by microbial infections affect hundreds of millions of children and adults throughout the world. In Western populations, the treatment of lung infections is a primary driver of antibiotic resistance. Traditional therapeutic strategies have been based on the premise that the healthy lung is sterile and that infections grow in a pristine environment. As a consequence, rapid advances in our understanding of the composition of the microbiota of the skin and bowel have not yet been matched by studies of the respiratory tree. The recognition that the lungs are as populated with microorganisms as other mucosal surfaces provides the opportunity to reconsider the mechanisms and management of lung infections. Molecular analyses of the lung microbiota are revealing profound adverse responses to widespread antibiotic use, urbanization and globalization. This Opinion article proposes how technologies and concepts flowing from the Human Microbiome Project can transform the diagnosis and treatment of common lung diseases.}, } @article {pmid29061469, year = {2018}, author = {Yanai, I}, title = {Development and Evolution through the Lens of Global Gene Regulation.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {11-20}, doi = {10.1016/j.tig.2017.09.011}, pmid = {29061469}, issn = {0168-9525}, mesh = {Animals ; *Biological Evolution ; Embryonic Development/*genetics ; *Gene Expression Regulation, Developmental ; Germ Layers ; Phylogeny ; }, abstract = {Evolution and development are two inherently intertwined processes. As the embryo develops it does so in ways that both reflect past constraints and bias the future evolution of the species. While research exploiting this insight typically studies individual genes, transcriptomic analyses have sparked a new wave of discoveries. In this opinion piece, I review the evidence arising from transcriptomics on the topics of the evolution of germ layers, the phylotypic stage, and developmental constraints. The spatiotemporal pattern of gene expression across germ layers provides evidence that the endoderm was the first germ layer to evolve. Comparing transcriptome dynamics throughout developmental time across distant species reveals a mid-developmental transition under strong developmental constraints. These studies highlight the efficiency of exploratory data analysis using computational tools and comparative approaches for discovery.}, } @article {pmid29058043, year = {2018}, author = {Chi, H and Holo, H}, title = {Synergistic Antimicrobial Activity Between the Broad Spectrum Bacteriocin Garvicin KS and Nisin, Farnesol and Polymyxin B Against Gram-Positive and Gram-Negative Bacteria.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {272-277}, pmid = {29058043}, issn = {1432-0991}, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteriocins/pharmacology ; Drug Synergism ; Farnesol/*pharmacology ; Gram-Negative Bacteria/*drug effects/growth & development ; Gram-Positive Bacteria/*drug effects/growth & development ; Microbial Sensitivity Tests ; Nisin/*pharmacology ; Polymyxin B/*pharmacology ; }, abstract = {The increasing emergence of antibiotics resistance is of global concern. Finding novel antimicrobial agents and strategies based on synergistic combinations are essential to combat resistant bacteria. We evaluated the activity of garvicin KS, a new bacteriocin produced by Lactococcus garvieae. The bacteriocin has a broad inhibitory spectrum, inhibiting members of all the 19 species of Gram-positive bacteria tested. Unlike other bacteriocins from Gram-positive bacteria, garvicin KS inhibits Acinetobacter but not other Gram-negative bacteria. Garvicin KS was tested in combination with other antimicrobial agents. We demonstrated synergy with polymyxin B against Acinetobacter spp. and Escherichia coli, but not against Pseudomonas aeruginosa. Similar effects were seen with mixtures of nisin and polymyxin B. The synergistic mixtures of all three components caused rapid killing and full eradication of Acinetobacter spp. and E. coli. In addition, garvicin KS and nisin also acted synergistically against Staphylococcus aureus, indicating different in modes of action between the two bacteriocins. Both bacteriocins showed synergy with farnesol, and the combination of low concentrations of garvicin KS, nisin and farnesol caused rapid eradication of all the S. aureus strains tested. Its broad inhibitory spectrum, rapid killing, and synergy with other antimicrobials makes garvicin KS a promising antimicrobial.}, } @article {pmid29056478, year = {2018}, author = {da Silva, JL and Nguyen, J and Fennelly, KP and Zelazny, AM and Olivier, KN}, title = {Survival of pathogenic Mycobacterium abscessus subsp. massiliense in Acanthamoeba castellanii.}, journal = {Research in microbiology}, volume = {169}, number = {1}, pages = {56-60}, pmid = {29056478}, issn = {1769-7123}, support = {Z99 HL999999/NULL/Intramural NIH HHS/United States ; ZIA HL006200-01/NULL/Intramural NIH HHS/United States ; ZIA HL006200-02/NULL/Intramural NIH HHS/United States ; }, mesh = {Acanthamoeba castellanii/*microbiology/physiology ; Humans ; *Microbial Viability ; Models, Animal ; Mycobacterium Infections, Nontuberculous/*microbiology ; Mycobacterium abscessus/*growth & development/physiology ; }, abstract = {We used an amoeba model to study the intracellular growth and cytotoxicity of clinical strains of Mycobacterium abscessus subsp. massiliense (Mabsm) isolated from 2 patients (one with cystic fibrosis, the other one with idiopathic bronchiectasis) during the early (smooth colonies) and late stage (rough colonies) of chronic pulmonary infection. Acanthamoeba castellanii were infected with Mabsm (MOI 100) and samples collected every 24 h for 72 h. Results showed Mabsm is able to survive in trophozoites and persist in cysts for at least 7 days. Late Mabsm demonstrated higher cytotoxicity toward A. castellanii when compared to early strains. A. castellanii is a useful in vitro host model to study infection of Mabsm clinical isolates.}, } @article {pmid29056293, year = {2018}, author = {Caccamo, PD and Brun, YV}, title = {The Molecular Basis of Noncanonical Bacterial Morphology.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {191-208}, pmid = {29056293}, issn = {1878-4380}, support = {R35 GM122556/GM/NIGMS NIH HHS/United States ; R01 GM113172/GM/NIGMS NIH HHS/United States ; }, mesh = {Bacteria/*cytology ; *Bacterial Physiological Phenomena ; Biological Evolution ; Cell Plasticity ; Cell Wall/physiology ; *Models, Biological ; Peptidoglycan/metabolism ; Species Specificity ; }, abstract = {Bacteria come in a wide variety of shapes and sizes. The true picture of bacterial morphological diversity is likely skewed due to an experimental focus on pathogens and industrially relevant organisms. Indeed, most of the work elucidating the genes and molecular processes involved in maintaining bacterial morphology has been limited to rod- or coccal-shaped model systems. The mechanisms of shape evolution, the molecular processes underlying diverse shapes and growth modes, and how individual cells can dynamically modulate their shape are just beginning to be revealed. Here we discuss recent work aimed at advancing our knowledge of shape diversity and uncovering the molecular basis for shape generation in noncanonical and morphologically complex bacteria.}, } @article {pmid29055947, year = {2018}, author = {}, title = {Preface.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {5-6}, doi = {10.1159/000480746}, pmid = {29055947}, issn = {1661-5433}, mesh = {Disorders of Sex Development/genetics/parasitology/*pathology/therapy ; Humans ; Sexual Development ; }, } @article {pmid29055522, year = {2018}, author = {Campbell, SJ and Biritwum, NK and Woods, G and Velleman, Y and Fleming, F and Stothard, JR}, title = {Tailoring Water, Sanitation, and Hygiene (WASH) Targets for Soil-Transmitted Helminthiasis and Schistosomiasis Control.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {53-63}, doi = {10.1016/j.pt.2017.09.004}, pmid = {29055522}, issn = {1471-5007}, mesh = {Disease Eradication/*methods/standards/trends ; Helminthiasis/*prevention & control/transmission ; Humans ; Hygiene/*standards ; Sanitation/*standards/trends ; Schistosomiasis/*prevention & control/transmission ; Soil/parasitology ; Water/*parasitology ; World Health Organization ; }, abstract = {The World Health Organization's (WHO) 2015-2020 Global Strategy on water, sanitation, and hygiene (WASH) and neglected tropical diseases (NTDs) encourages integration, whilst maintaining existing structured NTD investments, and acceleration towards Sustainable Development Goal (SDG) targets. Accordingly, SDG-associated and WASH-NTD indicators have been developed, commencing important intersectoral dialogue, alongside opportunities for future disease-specific refinements. The rationale for soil-transmitted helminthiasis (STH)- and schistosomiasis-specific WASH considerations, and a traffic-light figure, are presented here to indicate where current international definitions may, or may not, suffice. Certain unique aspects in control dynamics and parasitic lifecycles, however, necessitate additional implementation research with more appropriate measurement indicators developed to record programmatic interventions and to define strategic priorities more effectively.}, } @article {pmid29055134, year = {2018}, author = {Parker, AJ and Williams, NM and Thomson, JD}, title = {Geographic patterns and pollination ecotypes in Claytonia virginica.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {202-210}, doi = {10.1111/evo.13381}, pmid = {29055134}, issn = {1558-5646}, abstract = {Geographical variation in pollinators visiting a plant can produce plant populations adapted to local pollinator environments. We documented two markedly different pollinator climates for the spring ephemeral wildflower Claytonia virginica: in more northern populations, the pollen-specialist bee Andrena erigeniae dominated, but in more southern populations, A. erigeniae visited rarely and the bee-fly Bombylius major dominated. Plants in the northern populations experienced faster pollen depletion than plants in southern populations. We also measured divergent pollen-related plant traits; plants in northern populations produced relatively more pollen per flower and anther dehiscence was more staggered than plants in southern populations. These plant traits might function to increase pollen dispersal via the different pollen vectors.}, } @article {pmid29055133, year = {2018}, author = {Meyer, ALS and Wiens, JJ}, title = {Estimating diversification rates for higher taxa: BAMM can give problematic estimates of rates and rate shifts.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {39-53}, doi = {10.1111/evo.13378}, pmid = {29055133}, issn = {1558-5646}, abstract = {Estimates of diversification rates are invaluable for many macroevolutionary studies. Recently, an approach called BAMM (Bayesian Analysis of Macro-evolutionary Mixtures) has become widely used for estimating diversification rates and rate shifts. At the same time, several articles have concluded that estimates of net diversification rates from the method-of-moments (MS) estimators are inaccurate. Yet, no studies have compared the ability of these two methods to accurately estimate clade diversification rates. Here, we use simulations to compare their performance. We found that BAMM yielded relatively weak relationships between true and estimated diversification rates. This occurred because BAMM underestimated the number of rates shifts across each tree, and assigned high rates to small clades with low rates. Errors in both speciation and extinction rates contributed to these errors, showing that using BAMM to estimate only speciation rates is also problematic. In contrast, the MS estimators (particularly using stem group ages), yielded stronger relationships between true and estimated diversification rates, by roughly twofold. Furthermore, the MS approach remained relatively accurate when diversification rates were heterogeneous within clades, despite the widespread assumption that it requires constant rates within clades. Overall, we caution that BAMM may be problematic for estimating diversification rates and rate shifts.}, } @article {pmid29055069, year = {2018}, author = {Galván, I}, title = {Evidence of evolutionary optimization of fatty acid length and unsaturation.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {172-176}, doi = {10.1111/jeb.13198}, pmid = {29055069}, issn = {1420-9101}, mesh = {Animals ; *Biological Evolution ; *Birds ; Cell Membrane/*chemistry ; Fatty Acids, Unsaturated/*chemistry/*metabolism ; *Models, Biological ; Selection, Genetic ; }, abstract = {The lipid composition of cell membranes exerts a crucial influence on cell physiology. Indeed, one double bond triggers membrane fluidity, essential for cell functionality, but additional double bonds increase the susceptibility to peroxidation, which produces reactive compounds that impair the viability of cells. It has therefore been suggested, but never tested in an extensive comparative context, that the composition of membrane fatty acids has been optimized during evolution. A similar prediction has been made for fatty acid chain length, on which susceptibility to peroxidation also depends. Here I tested for stabilizing selection on fatty acid composition by evaluating the fitting of the single stationary peak (SSP) model of evolution to a large data set from 107 species of birds, against alternative evolutionary models. I found that across-species variation in average chain length and in the proportion of monounsaturated fatty acids (MUFAs), but not in the proportion of polyunsaturated (PUFAs) nor saturated (SFAs) fatty acids, was better explained by SSP models than by other models. Results show optimum values of fatty acid chain length and proportion of MUFAs of 18 C atoms and 25.5% mol, respectively, the strength of stabilizing selection being particularly high in chain length. This is the first evidence of evolutionary optimization in fatty acid composition, suggesting that certain values may have been selected because of their adaptive capacity to minimize susceptibility to lipid peroxidation.}, } @article {pmid29055057, year = {2018}, author = {Lehnert, SJ and Helou, L and Pitcher, TE and Heath, JW and Heath, DD}, title = {Sperm competition, but not major histocompatibility divergence, drives differential fertilization success between alternative reproductive tactics in Chinook salmon.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {88-97}, doi = {10.1111/jeb.13199}, pmid = {29055057}, issn = {1420-9101}, mesh = {Animals ; Female ; Fertilization/*physiology ; Major Histocompatibility Complex/genetics ; Male ; Salmon/genetics/*physiology ; Sexual Behavior, Animal/*physiology ; Spermatozoa/*physiology ; }, abstract = {Post-copulatory sexual selection processes, including sperm competition and cryptic female choice (CFC), can operate based on major histocompatibility (MH) genes. We investigated sperm competition between male alternative reproductive tactics [jack (sneaker) and hooknose (guard)] of Chinook salmon (Oncorhynchus tshawytscha). Using a full factorial design, we examined in vitro competitive fertilization success of paired jack and hooknose males at three time points after sperm activation (0, 15 and 60 s) to test for male competition, CFC and time effects on male fertilization success. We also examined egg-mediated CFC at two MH genes by examining both the relationship between competitive fertilization success and MH divergence as well as inheritance patterns of MH alleles in resulting offspring. We found that jacks sired more offspring than hooknose males at 0 s post-activation; however, jack fertilization success declined over time post-activation, suggesting a trade-off between sperm speed and longevity. Enhanced fertilization success of jacks (presumably via higher sperm quality) may serve to increase sneaker tactic competitiveness relative to dominant hooknose males. We also found evidence of egg-mediated CFC (i.e. female × male interaction) influencing competitive fertilization success; however, CFC was not acting on the MH genes as we found no relationship between fertilization success and MH II β1 or MH I α1 divergence and we found no deviations from Mendelian inheritance of MH alleles in the offspring. Our study provides insight into evolutionary mechanisms influencing variation in male mating success within alternative reproductive tactics, thus underscoring different strategies that males can adopt to attain success.}, } @article {pmid29054811, year = {2018}, author = {Silva, SR and Gibson, R and Adamec, L and Domínguez, Y and Miranda, VFO}, title = {Molecular phylogeny of bladderworts: A wide approach of Utricularia (Lentibulariaceae) species relationships based on six plastidial and nuclear DNA sequences.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {244-264}, doi = {10.1016/j.ympev.2017.10.010}, pmid = {29054811}, issn = {1095-9513}, mesh = {Base Sequence ; Bayes Theorem ; Biological Evolution ; Cell Nucleus/genetics ; DNA, Plant/*chemistry/isolation & purification/metabolism ; Lamiales/classification/*genetics ; Phylogeny ; Plant Proteins/classification/genetics/metabolism ; Plastids/*genetics ; Ribulose-Bisphosphate Carboxylase/classification/genetics/metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The carnivorous plant genus Utricularia L. (bladderwort) comprises about 240 species distributed worldwide and is traditionally classified into two subgenera (Polypompholyx and Utricularia) and 35 sections, based mainly on general and trap morphology. It is one out of the largest carnivorous genera, representing ca. 30% of all carnivorous plant species, and is also the most widely distributed. According to previous phylogenetic studies, most infrageneric sections are monophyletic, but there are several incongruences considering their relationships and also the dissenting position of some species as a result of a too few (mostly one or two) molecular markers analyzed. Thus, here we present a multilocus phylogeny for Utricularia species with a wide taxonomic sampling (78 species and 115 accessions) based on six plastid (rbcL, matK, rpl20-rps12, rps16, trnL-F) and nuclear DNA (ITS region) sequences. The aim is to reconstruct a well-resolved tree to propose evolutionary and biogeographic hypotheses for the radiation of lineages with inferences about the divergence times of clades using a molecular clock approach.}, } @article {pmid29054463, year = {2018}, author = {Wang, B and Lv, Y and Li, X and Lin, Y and Deng, H and Pan, L}, title = {Profiling of secondary metabolite gene clusters regulated by LaeA in Aspergillus niger FGSC A1279 based on genome sequencing and transcriptome analysis.}, journal = {Research in microbiology}, volume = {169}, number = {2}, pages = {67-77}, doi = {10.1016/j.resmic.2017.10.002}, pmid = {29054463}, issn = {1769-7123}, mesh = {Aspergillus niger/*genetics/*metabolism ; Fungal Proteins/*genetics/metabolism ; Gene Expression Regulation, Fungal ; Genome, Fungal ; Multigene Family ; Polyketides/metabolism ; *Secondary Metabolism ; Transcription Factors/*genetics/metabolism ; }, abstract = {The global regulator LaeA controls the production of many fungal secondary metabolites, possibly via chromatin remodeling. Here we aimed to survey the secondary metabolite profile regulated by LaeA in Aspergillus niger FGSC A1279 by genome sequencing and comparative transcriptomics between the laeA deletion (ΔlaeA) and overexpressing (OE-laeA) mutants. Genome sequencing revealed four putative polyketide synthase genes specific to FGSC A1279, suggesting that the corresponding polyketide compounds might be unique to FGSC A1279. RNA-seq data revealed 281 putative secondary metabolite genes upregulated in the OE-laeA mutants, including 22 secondary metabolite backbone genes. LC-MS chemical profiling illustrated that many secondary metabolites were produced in OE-laeA mutants compared to wild type and ΔlaeA mutants, providing potential resources for drug discovery. KEGG analysis annotated 16 secondary metabolite clusters putatively linked to metabolic pathways. Furthermore, 34 of 61 Zn2Cys6 transcription factors located in secondary metabolite clusters were differentially expressed between ΔlaeA and OE-laeA mutants. Three secondary metabolite clusters (cluster 18, 30 and 33) containing Zn2Cys6 transcription factors that were upregulated in OE-laeA mutants were putatively linked to KEGG pathways, suggesting that Zn2Cys6 transcription factors might play an important role in synthesizing secondary metabolites regulated by LaeA. Taken together, LaeA dramatically influences the secondary metabolite profile in FGSC A1279.}, } @article {pmid29054341, year = {2018}, author = {Rossey, I and McLellan, JS and Saelens, X and Schepens, B}, title = {Clinical Potential of Prefusion RSV F-specific Antibodies.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {209-219}, doi = {10.1016/j.tim.2017.09.009}, pmid = {29054341}, issn = {1878-4380}, mesh = {Animals ; Antibodies, Monoclonal/immunology/pharmacology ; Antibodies, Neutralizing/immunology/pharmacology ; Antibodies, Viral/*immunology/pharmacology ; Antigens, Viral/*immunology ; Humans ; Immunization ; Models, Molecular ; Protein Conformation ; Recombinant Proteins ; Respiratory Syncytial Virus Infections/*immunology/*prevention & control ; Respiratory Syncytial Virus, Human/genetics/*immunology ; Viral Fusion Proteins/chemistry/genetics/*immunology ; Virus Internalization ; }, abstract = {Human respiratory syncytial virus (RSV) is the leading cause of lower respiratory tract infections in the very young. The RSV fusion protein (F) is essential for virus entry because it mediates viral and host membrane fusion. During this fusion process F is converted from a metastable prefusion conformation into an energetically favored postfusion state. Antibodies that target F can prevent viral entry and reduce disease caused by RSV. During recent years, many prefusion F-specific antibodies have been described. These antibodies typically have stronger RSV-neutralizing activity compared to those that also bind F in the postfusion conformation. Here, we describe how F-specific antibodies protect against RSV and why specifically targeting prefusion F could have great clinical potential.}, } @article {pmid29052965, year = {2018}, author = {Morrison-Whittle, P and Goddard, MR}, title = {From vineyard to winery: a source map of microbial diversity driving wine fermentation.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {75-84}, doi = {10.1111/1462-2920.13960}, pmid = {29052965}, issn = {1462-2920}, abstract = {Humans have been making wine for thousands of years and microorganisms play an integral part in this process as they not only drive fermentation, but also significantly influence the flavour, aroma and quality of finished wines. Since fruits are ephemeral, they cannot comprise a permanent microbial habitat; thus, an age-old unanswered question concerns the origin of fruit and ferment associated microbes. Here we use next-generation sequencing approaches to examine and quantify the roles of native forest, vineyard soil, bark and fruit habitats as sources of fungal diversity in ferments. We show that microbial communities in harvested juice and ferments vary significantly across regions, and that while vineyard fungi account for ∼40% of the source of this diversity, uncultivated ecosystems outside of vineyards also prove a significant source. We also show that while communities in harvested juice resemble those found on grapes, these increasingly resemble fungi present on vine bark as the ferment proceeds.}, } @article {pmid29052931, year = {2018}, author = {Hernández-Prieto, MA and Li, Y and Postier, BL and Blankenship, RE and Chen, M}, title = {Far-red light promotes biofilm formation in the cyanobacterium Acaryochloris marina.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {535-545}, doi = {10.1111/1462-2920.13961}, pmid = {29052931}, issn = {1462-2920}, abstract = {Light quantity and quality promotes ecological-niche differentiation of photosynthetic organisms. The existence of cyanobacteria capable of performing photosynthesis using red-shifted chlorophylls, chlorophyll d and f, reduces competition between species in light-limiting environments, and permits them to thrive in niches enriched in far-red light. We examined global transcriptome changes due to changing the culture light conditions in Acaryochloris marina, a chlorophyll d-containing cyanobacterium. We identified the functional category of 'photosynthesis' as the most down-regulated and the category of 'cell wall/membrane biogenesis' as the most up-regulated through a functional enrichment analysis of genes differentially expressed. Within the category of 'cell wall/membrane biogenesis', genes encoding glycosysltransferases accumulated the most in response to far-red light. Further experimental results confirmed that cells grown under far-red light form biofilms with a significantly increased adherence compared to cells grown under white light. Taken together, these results indicate that Acaryochloris marina shifts its lifestyle from a planktonic state under white light to an immobilized state under far-red light.}, } @article {pmid29051980, year = {2018}, author = {Douriet-Gámez, NR and Maldonado-Mendoza, IE and Ibarra-Laclette, E and Blom, J and Calderón-Vázquez, CL}, title = {Genomic Analysis of Bacillus sp. Strain B25, a Biocontrol Agent of Maize Pathogen Fusarium verticillioides.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {247-255}, pmid = {29051980}, issn = {1432-0991}, support = {2009-2013//Fundación Produce Sinaloa/ ; Secretaría de Investigación y Posgrado 2014103//Instituto Politécnico Nacional/ ; 20144021//Instituto Politécnico Nacional/ ; 20150118//Instituto Politécnico Nacional/ ; CVU 230688//Consejo Nacional de Ciencia y Tecnología/ ; }, mesh = {*Antibiosis ; Bacillus/classification/*genetics/physiology ; Fusarium/*physiology ; *Genome, Bacterial ; Genomics ; Phylogeny ; Plant Diseases/*microbiology/prevention & control ; Zea mays/*microbiology ; }, abstract = {Bacillus sp. B25 is an effective biocontrol agent against the maize pathogenic fungus Fusarium verticillioides (Fv). Previous in vitro assays have shown that B25 has protease, glucanase, and chitinase activities and siderophores production; however, specific mechanisms by which B25 controls Fv are still unknown. To determine the genetic traits involved in biocontrol, B25 genome was sequenced and analyzed. B25 genome is composed of 5,113,413 bp and 5251 coding genes. A multilocus phylogenetic analysis (MLPA) suggests that B25 is closely related to the Bacillus cereus group and a high percentage (70-75%) of the genetic information is conserved between B25 and related strains, which include most of the genes associated to fungal antagonism. Some of these genes are shared with some biocontrol agents of the Bacillus genus and less with Pseudomonas and Serratia strains. We performed a genomic comparison between B25 and five Bacillus spp., Pseudomonas and Serratia strains. B25 contains genes involved in a wide variety of antagonistic mechanisms including chitinases, glycoside hydrolases, siderophores, antibiotics, and biofilm production that could be implicated in root colonization. Also, 24 genomic islands and 3 CRISPR sequences were identified in the B25 genome. This is the first comparative genome analysis between strains belonging to the B. cereus group and biocontrol agents of phytopathogenic fungi. These results are the starting point for further studies on B25 gene expression during its interaction with Fv.}, } @article {pmid29049916, year = {2018}, author = {Hen-Avivi, S and Avraham, R}, title = {Immune cell type 'fingerprints' at the basis of outcome diversity of human infection.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {31-39}, doi = {10.1016/j.mib.2017.09.012}, pmid = {29049916}, issn = {1879-0364}, mesh = {Anti-Bacterial Agents/adverse effects/therapeutic use ; Communicable Diseases/*immunology ; Disease Susceptibility/immunology/microbiology ; High-Throughput Nucleotide Sequencing/methods ; Host-Pathogen Interactions/*immunology ; Humans ; Immune System/*cytology ; Single-Cell Analysis/methods ; }, abstract = {Despite the availability of antibiotics and immunization, infectious diseases remain a major cause of malignancy and death worldwide. Yet, it is well documented that for most infectious agents, clinical disease develops in only a small minority of infected individuals. There is, in fact, great heterogeneity in infection outcome, from complete clearance of the pathogen to severe illness. Understanding this variation remains elusive, despite its great potential to equip us with new tools for the treatment of infectious diseases. Here, we propose a novel perspective for studying this diversity in human infection outcome, one that utilizes single-cell analysis technologies. Recent advances in single-cell RNA-seq technologies allow the detection of rare subpopulations that play important roles in host-pathogen interactions. We propose that applying single-cell RNA-seq to the study of infection can provide a 'fingerprint' of the immune cell types that are associated with the ability of the host to clear a pathogen and, thereby, broaden our current understanding of variation in susceptibility to infection within the population.}, } @article {pmid29048573, year = {2018}, author = {Turissini, DA and McGirr, JA and Patel, SS and David, JR and Matute, DR}, title = {The Rate of Evolution of Postmating-Prezygotic Reproductive Isolation in Drosophila.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {312-334}, pmid = {29048573}, issn = {1537-1719}, support = {R01 GM121750/GM/NIGMS NIH HHS/United States ; }, abstract = {Reproductive isolation is an intrinsic aspect of species formation. For that reason, the identification of the precise isolating traits, and the rates at which they evolve, is crucial to understanding how species originate and persist. Previous work has measured the rates of evolution of prezygotic and postzygotic barriers to gene flow, yet no systematic analysis has studied the rates of evolution of postmating-prezygotic (PMPZ) barriers. We measured the magnitude of two barriers to gene flow that act after mating occurs but before fertilization. We also measured the magnitude of a premating barrier (female mating rate in nonchoice experiments) and two postzygotic barriers (hybrid inviability and hybrid sterility) for all pairwise crosses of all nine known extant species within the melanogaster subgroup. Our results indicate that PMPZ isolation evolves faster than hybrid inviability but slower than premating isolation. Next, we partition postzygotic isolation into different components and find that, as expected, hybrid sterility evolves faster than hybrid inviability. These results lend support for the hypothesis that, in Drosophila, reproductive isolation mechanisms (RIMs) that act early in reproduction (or in development) tend to evolve faster than those that act later in the reproductive cycle. Finally, we tested whether there was evidence for reinforcing selection at any RIM. We found no evidence for generalized evolution of reproductive isolation via reinforcement which indicates that there is no pervasive evidence of this evolutionary process. Our results indicate that PMPZ RIMs might have important evolutionary consequences in initiating speciation and in the persistence of new species.}, } @article {pmid29048557, year = {2018}, author = {Duan, Y and Dou, S and Zhang, H and Wu, C and Wu, M and Lu, J}, title = {Linkage of A-to-I RNA Editing in Metazoans and the Impact on Genome Evolution.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {132-148}, pmid = {29048557}, issn = {1537-1719}, abstract = {The adenosine-to-inosine (A-to-I) RNA editomes have been systematically characterized in various metazoan species, and many editing sites were found in clusters. However, it remains unclear whether the clustered editing sites tend to be linked in the same RNA molecules or not. By adopting a method originally designed to detect linkage disequilibrium of DNA mutations, we examined the editomes of ten metazoan species and detected extensive linkage of editing in Drosophila and cephalopods. The prevalent linkages of editing in these two clades, many of which are conserved between closely related species and might be associated with the adaptive proteomic recoding, are maintained by natural selection at the cost of genome evolution. Nevertheless, in worms and humans, we only detected modest proportions of linked editing events, the majority of which were not conserved. Furthermore, the linkage of editing in coding regions of worms and humans might be overall deleterious, which drives the evolution of DNA sites to escape promiscuous editing. Altogether, our results suggest that the linkage landscape of A-to-I editing has evolved during metazoan evolution. This present study also suggests that linkage of editing should be considered in elucidating the functional consequences of RNA editing.}, } @article {pmid29045724, year = {2018}, author = {Dapper, AL and Payseur, BA}, title = {Effects of Demographic History on the Detection of Recombination Hotspots from Linkage Disequilibrium.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {335-353}, pmid = {29045724}, issn = {1537-1719}, support = {R01 GM100426/GM/NIGMS NIH HHS/United States ; R01 GM120051/GM/NIGMS NIH HHS/United States ; T32 HG002760/HG/NHGRI NIH HHS/United States ; }, abstract = {In some species, meiotic recombination is concentrated in small genomic regions. These "recombination hotspots" leave signatures in fine-scale patterns of linkage disequilibrium, raising the prospect that the genomic landscape of hotspots can be characterized from sequence variation. This approach has led to the inference that hotspots evolve rapidly in some species, but are conserved in others. Historic demographic events, such as population bottlenecks, are known to affect patterns of linkage disequilibrium across the genome, violating population genetic assumptions of this approach. Although such events are prevalent, demographic history is generally ignored when making inferences about the evolution of recombination hotspots. To determine the effect of demography on the detection of recombination hotspots, we use the coalescent to simulate haplotypes with a known recombination landscape. We measure the ability of popular linkage disequilibrium-based programs to detect hotspots across a range of demographic histories, including population bottlenecks, hidden population structure, population expansions, and population contractions. We find that demographic events have the potential to greatly reduce the power and increase the false positive rate of hotspot discovery. Neither the power nor the false positive rate of hotspot detection can be predicted without also knowing the demographic history of the sample. Our results suggest that ignoring demographic history likely overestimates the power to detect hotspots and therefore underestimates the degree of hotspot sharing between species. We suggest strategies for incorporating demographic history into population genetic inferences about recombination hotspots.}, } @article {pmid29044885, year = {2018}, author = {Winney, IS and Schroeder, J and Nakagawa, S and Hsu, YH and Simons, MJP and Sánchez-Tójar, A and Mannarelli, ME and Burke, T}, title = {Heritability and social brood effects on personality in juvenile and adult life-history stages in a wild passerine.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {75-87}, doi = {10.1111/jeb.13197}, pmid = {29044885}, issn = {1420-9101}, mesh = {Animals ; Behavior, Animal/*physiology ; Personality ; Quantitative Trait, Heritable ; Social Behavior ; Sparrows/genetics/*physiology ; }, abstract = {How has evolution led to the variation in behavioural phenotypes (personalities) in a population? Knowledge of whether personality is heritable, and to what degree it is influenced by the social environment, is crucial to understanding its evolutionary significance, yet few estimates are available from natural populations. We tracked three behavioural traits during different life-history stages in a pedigreed population of wild house sparrows. Using a quantitative genetic approach, we demonstrated heritability in adult exploration, and in nestling activity after accounting for fixed effects, but not in adult boldness. We did not detect maternal effects on any traits, but we did detect a social brood effect on nestling activity. Boldness, exploration and nestling activity in this population did not form a behavioural syndrome, suggesting that selection could act independently on these behavioural traits in this species, although we found no consistent support for phenotypic selection on these traits. Our work shows that repeatable behaviours can vary in their heritability and that social context influences personality traits. Future efforts could separate whether personality traits differ in heritability because they have served specific functional roles in the evolution of the phenotype or because our concept of personality and the stability of behaviour needs to be revised.}, } @article {pmid29044818, year = {2018}, author = {Devigili, A and Fitzpatrick, JL and Gasparini, C and Ramnarine, IW and Pilastro, A and Evans, JP}, title = {Possible glimpses into early speciation: the effect of ovarian fluid on sperm velocity accords with post-copulatory isolation between two guppy populations.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {66-74}, doi = {10.1111/jeb.13194}, pmid = {29044818}, issn = {1420-9101}, mesh = {Animals ; Body Fluids/physiology ; Female ; Fertilization/*physiology ; Genetic Speciation ; Male ; Ovary/*physiology ; Poecilia/*classification/genetics ; Sexual Behavior, Animal ; Spermatozoa/*physiology ; Trinidad and Tobago ; }, abstract = {Identifying mechanisms of reproductive isolation is key to understanding speciation. Among the putative mechanisms underlying reproductive isolation, sperm-female interactions (post-mating-prezygotic barriers) are arguably the hardest to identify, not least because these are likely to operate at the cellular or molecular level. Yet sperm-female interactions offer great potential to prevent the transfer of genetic information between different populations at the initial stages of speciation. Here, we provide a preliminary test for the presence of a putative post-mating-prezygotic barrier operating between three populations of Trinidadian guppies (Poecilia reticulata), an internally fertilizing fish that inhabits streams with different levels of connectivity across Trinidad. We experimentally evaluate the effect of female ovarian fluid on sperm velocity (a predictor of competitive fertilization success) according to whether males and females were from the same (native) or different (foreign) populations. Our results reveal the potential for ovarian fluid to act as a post-mating-prezygotic barrier between two populations from different drainages, but also that the strength of this barrier is different among populations. This result may explain the previous finding that, in some populations, sperm from native males have precedence over foreign sperm, which could eventually lead to reproductive isolation between these populations.}, } @article {pmid29044782, year = {2018}, author = {Burress, ED and Alda, F and Duarte, A and Loureiro, M and Armbruster, JW and Chakrabarty, P}, title = {Phylogenomics of pike cichlids (Cichlidae: Crenicichla): the rapid ecological speciation of an incipient species flock.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {14-30}, doi = {10.1111/jeb.13196}, pmid = {29044782}, issn = {1420-9101}, mesh = {Animals ; Biodiversity ; Cichlids/anatomy & histology/*classification/genetics ; Genetic Speciation ; Genome ; *Phylogeny ; Rivers ; South America ; Species Specificity ; }, abstract = {The rapid rise of phenotypic and ecological diversity in independent lake-dwelling groups of cichlids is emblematic of the East African Great Lakes. In this study, we show that similar ecologically based diversification has occurred in pike cichlids (Crenicichla) throughout the Uruguay River drainage of South America. We collected genomic data from nearly 500 ultraconserved element (UCEs) loci and >260 000 base pairs across 33 species, to obtain a phylogenetic hypothesis for the major species groups and to evaluate the relationships and genetic structure among five closely related, endemic, co-occurring species (the Uruguay River species flock; URSF). Additionally, we evaluated ecological divergence of the URSF based on body and lower pharyngeal jaw (LPJ) shape and gut contents. Across the genus, we recovered novel relationships among the species groups. We found strong support for the monophyly of the URSF; however, relationships among these species remain problematic, likely because of the rapid and recent evolution of this clade. Clustered co-ancestry analysis recovered most species as well delimited genetic groups. The URSF species exhibit species-specific body and LPJ shapes associated with specialized trophic roles. Collectively, our results suggest that the URSF consists of incipient species that arose via ecological speciation associated with the exploration of novel trophic roles.}, } @article {pmid29043597, year = {2018}, author = {Márquez-Corro, JI and Escudero, M and Luceño, M}, title = {Do holocentric chromosomes represent an evolutionary advantage? A study of paired analyses of diversification rates of lineages with holocentric chromosomes and their monocentric closest relatives.}, journal = {Chromosome research : an international journal on the molecular, supramolecular and evolutionary aspects of chromosome biology}, volume = {26}, number = {3}, pages = {139-152}, pmid = {29043597}, issn = {1573-6849}, support = {CGL2016-77401-P//Spanish Ministry of Economy and Competitiveness/International ; }, mesh = {Animals ; Arthropods/*genetics ; Chromosomes, Insect/*genetics ; Chromosomes, Plant/*genetics ; *Evolution, Molecular ; Magnoliopsida/*genetics ; Nematoda/*genetics ; }, abstract = {Despite most of the cytogenetic research is focused on monocentric chromosomes, chromosomes with kinetochoric activity localized in a single centromere, several studies have been centered on holocentric chromosomes which have diffuse kinetochoric activity along the chromosomes. The eukaryotic organisms that present this type of chromosomes have been relatively understudied despite they constitute rather diversified species lineages. On the one hand, holocentric chromosomes may present intrinsic benefits (chromosome mutations such as fissions and fusions are potentially neutral in holocentrics). On the other hand, they present restrictions to the spatial separation of the functions of recombination and segregation during meiotic divisions (functions that may interfere), separation that is found in monocentric chromosomes. In this study, we compare the diversification rates of all known holocentric lineages in animals and plants with their most related monocentric lineages in order to elucidate whether holocentric chromosomes constitute an evolutionary advantage in terms of diversification and species richness. The results showed that null hypothesis of equal mean diversification rates cannot be rejected, leading us to surmise that shifts in diversification rates between holocentric and monocentric lineages might be due to other factors, such as the idiosyncrasy of each lineage or the interplay of evolutionary selections with the benefits of having either monocentric or holocentric chromosomes.}, } @article {pmid29043388, year = {2018}, author = {Montaño-Salazar, SM and Lizarazo-Marriaga, J and Brandão, PFB}, title = {Isolation and Potential Biocementation of Calcite Precipitation Inducing Bacteria from Colombian Buildings.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {256-265}, pmid = {29043388}, issn = {1432-0991}, support = {DIB 19380/19381//Dirección de Investigación, Universidad Nacional de Colombia/ ; }, mesh = {Bacteria/classification/genetics/*isolation & purification/metabolism ; Calcium Carbonate/*chemistry ; Chemical Precipitation ; Colombia ; Construction Materials/analysis/*microbiology ; }, abstract = {Microbiological induced calcium carbonate or calcite precipitation (MICP) has become a highly researched issue due to its multiple applications in the construction industry, being a promising alternative with a great biotechnological importance. In this work, potential calcite precipitation inducing bacteria were isolated from mortar and concrete samples of different buildings at the National University of Colombia. Eighteen crystal-precipitating strains were recovered in Urea-CaCl2 solid medium. The 16S rRNA gene sequencing identified isolates as Arthrobacter, Psychrobacillus and Rhodococcus genera. It is reported, for the first time, the calcite precipitation by P. psycrodurans and R. qingshengii. Optical microscopy and Scanning Electron Microscopy showed crystals with irregular and spherical shapes, and beige and white colours. Furthermore, crystals formation appeared to be strain-specific. X-Ray diffraction analysis confirmed crystals composition as CaCO3. Biocementation tests showed that MICP treatments of mortar cubes using P. psycrodurans caused an increase in their compressive strength compared to control samples. The positive action of a native MICP strain in mortar blocks biomineralization is shown, which is of great interest and potential for the construction industry.}, } @article {pmid29040727, year = {2018}, author = {Liu, YH and Wang, L and Xu, T and Guo, X and Li, Y and Yin, TT and Yang, HC and Hu, Y and Adeola, AC and Sanke, OJ and Otecko, NO and Wang, M and Ma, Y and Charles, OS and Sinding, MS and Gopalakrishnan, S and Alfredo Samaniego, J and Hansen, AJ and Fernandes, C and Gaubert, P and Budd, J and Dawuda, PM and Knispel Rueness, E and Jiang, L and Zhai, W and Gilbert, MTP and Peng, MS and Qi, X and Wang, GD and Zhang, YP}, title = {Whole-Genome Sequencing of African Dogs Provides Insights into Adaptations against Tropical Parasites.}, journal = {Molecular biology and evolution}, volume = {35}, number = {2}, pages = {287-298}, doi = {10.1093/molbev/msx258}, pmid = {29040727}, issn = {1537-1719}, abstract = {Natural selection in domestic dogs is of great interest in evolutionary biology since dogs have migrated to every inhabited continent of the world alongside humans, and adapted to diverse environments. Here, we explored their demographic history and genetic basis of adaptation to the tropical African environment using whole genome analyses of 19 African indigenous dogs from Nigeria. Demographic analysis suggests that the ancestors of these dogs migrated into Africa from Eurasia 14,000 years ago and underwent a severe founder effect before population expansion. Admixture analysis further reveals that African dog genomes contain about 1.88-3.50% introgression from African golden wolves (Canis anthus). Population genetic analysis identifies 50 positively selected genes linked with immunity, angiogenesis, ultraviolet protection, as well as insulin secretion and sensitivity that may contribute to adaptation to tropical conditions. One of the positively selected genes, adhesion G protein-coupled receptor E1 (ADGRE1), has also been found to be association with severe malaria resistance in African human populations. Functional assessments showed that ADGRE1 provides protective host defense against Plasmodium infections. This result, together with the fact that the inflammatory response to canine babesiosis is similar to complicated falciparum malaria in humans, support the dogs as a model for the study of malaria control and treatment.}, } @article {pmid29040712, year = {2018}, author = {Parks, MB and Wickett, NJ and Alverson, AJ}, title = {Signal, Uncertainty, and Conflict in Phylogenomic Data for a Diverse Lineage of Microbial Eukaryotes (Diatoms, Bacillariophyta).}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {80-93}, pmid = {29040712}, issn = {1537-1719}, abstract = {Diatoms (Bacillariophyta) are a species-rich group of eukaryotic microbes diverse in morphology, ecology, and metabolism. Previous reconstructions of the diatom phylogeny based on one or a few genes have resulted in inconsistent resolution or low support for critical nodes. We applied phylogenetic paralog pruning techniques to a data set of 94 diatom genomes and transcriptomes to infer perennially difficult species relationships, using concatenation and summary-coalescent methods to reconstruct species trees from data sets spanning a wide range of thresholds for taxon and column occupancy in gene alignments. Conflicts between gene and species trees decreased with both increasing taxon occupancy and bootstrap cutoffs applied to gene trees. Concordance between gene and species trees was lowest for short internodes and increased logarithmically with increasing edge length, suggesting that incomplete lineage sorting disproportionately affects species tree inference at short internodes, which are a common feature of the diatom phylogeny. Although species tree topologies were largely consistent across many data treatments, concatenation methods appeared to outperform summary-coalescent methods for sparse alignments. Our results underscore that approaches to species-tree inference based on few loci are likely to be misled by unrepresentative sampling of gene histories, particularly in lineages that may have diversified rapidly. In addition, phylogenomic studies of diatoms, and potentially other hyperdiverse groups, should maximize the number of gene trees with high taxon occupancy, though there is clearly a limit to how many of these genes will be available.}, } @article {pmid29040697, year = {2018}, author = {Salvador-Martínez, I and Coronado-Zamora, M and Castellano, D and Barbadilla, A and Salazar-Ciudad, I}, title = {Mapping Selection within Drosophila melanogaster Embryo's Anatomy.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {66-79}, doi = {10.1093/molbev/msx266}, pmid = {29040697}, issn = {1537-1719}, abstract = {We present a survey of selection across Drosophila melanogaster embryonic anatomy. Our approach integrates genomic variation, spatial gene expression patterns, and development with the aim of mapping adaptation over the entire embryo's anatomy. Our adaptation map is based on analyzing spatial gene expression information for 5,969 genes (from text-based annotations of in situ hybridization data directly from the BDGP database, Tomancak et al. 2007) and the polymorphism and divergence in these genes (from the project DGRP, Mackay et al. 2012).The proportion of nonsynonymous substitutions that are adaptive, neutral, or slightly deleterious are estimated for the set of genes expressed in each embryonic anatomical structure using the distribution of fitness effects-alpha method (Eyre-Walker and Keightley 2009). This method is a robust derivative of the McDonald and Kreitman test (McDonald and Kreitman 1991). We also explore whether different anatomical structures differ in the phylogenetic age, codon usage, or expression bias of the genes they express and whether genes expressed in many anatomical structures show more adaptive substitutions than other genes.We found that: 1) most of the digestive system and ectoderm-derived structures are under selective constraint, 2) the germ line and some specific mesoderm-derived structures show high rates of adaptive substitution, and 3) the genes that are expressed in a small number of anatomical structures show higher expression bias, lower phylogenetic ages, and less constraint.}, } @article {pmid29040657, year = {2018}, author = {Moreno-Villena, JJ and Dunning, LT and Osborne, CP and Christin, PA}, title = {Highly Expressed Genes Are Preferentially Co-Opted for C4 Photosynthesis.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {94-106}, pmid = {29040657}, issn = {1537-1719}, abstract = {Novel adaptations are generally assembled by co-opting pre-existing genetic components, but the factors dictating the suitability of genes for new functions remain poorly known. In this work, we used comparative transcriptomics to determine the attributes that increased the likelihood of some genes being co-opted for C4 photosynthesis, a convergent complex trait that boosts productivity in tropical conditions. We show that independent lineages of grasses repeatedly co-opted the gene lineages that were the most highly expressed in non-C4 ancestors to produce their C4 pathway. Although ancestral abundance in leaves explains which genes were used for the emergence of a C4 pathway, the tissue specificity has surprisingly no effect. Our results suggest that levels of key genes were elevated during the early diversification of grasses and subsequently repeatedly used to trigger a weak C4 cycle via relatively few mutations. The abundance of C4-suitable transcripts therefore facilitated physiological innovation, but the transition to a strong C4 pathway still involved consequent changes in expression levels, leaf specificity, and coding sequences. The direction and amount of changes required for the strong C4 pathway depended on the identity of the genes co-opted, so that ancestral gene expression both facilitates adaptive transitions and constrains subsequent evolutionary trajectories.}, } @article {pmid29038844, year = {2018}, author = {Hou, J and Cui, HL}, title = {In Vitro Antioxidant, Antihemolytic, and Anticancer Activity of the Carotenoids from Halophilic Archaea.}, journal = {Current microbiology}, volume = {75}, number = {3}, pages = {266-271}, pmid = {29038844}, issn = {1432-0991}, support = {31600002//National Natural Science Foundation of China/ ; 31370054//National Natural Science Foundation of China/ ; }, mesh = {Animals ; Antineoplastic Agents/chemistry/metabolism/*pharmacology ; Antioxidants/chemistry/metabolism/*pharmacology ; Carotenoids/chemistry/metabolism/*pharmacology ; Cell Line ; Cell Survival/drug effects ; Erythrocytes/drug effects ; Factor VIII/chemistry/metabolism/*pharmacology ; Halobacteriaceae/*chemistry/classification/metabolism ; Humans ; Mice ; Sodium Chloride/metabolism ; }, abstract = {Halophilic archaea represent a promising natural source of carotenoids. However, little information is available about the biological effects of carotenoids from halophilic archaea. In this study, the carotenoids produced by seven halophilic archaeal strains Halogeometricum rufum, Halogeometricum limi, Haladaptatus litoreus, Haloplanus vescus, Halopelagius inordinatus, Halogranum rubrum, and Haloferax volcanii were identified by ultraviolet/visible spectroscopy, thin-layer chromatography, and high-performance liquid chromatography-tandem mass spectrometry. The C50 carotenoids bacterioruberin and its derivatives monoanhydrobacterioruberin and bisanhydrobacterioruberin were found to be the predominant carotenoids. The antioxidant capacities of the carotenoids from these strains were significantly higher than β-carotene as determined by 1,1-diphenyl-2-picrylhydrazyl radical scavenging assay. The antihemolytic activities of these carotenoid extracts against H2O2-induced hemolysis in mouse erythrocytes were 3.9-6.3 times higher than β-carotene. A dose-dependent in vitro antiproliferative activity against HepG2 cells was observed for the extract from Hgm. limi, while that from Hpn. vescus exhibited a relatively high activity in a dose-independent manner. These results suggested that halophilic archaea could be considered as an alternative source of natural carotenoids with high antioxidant, antihemolytic, and anticancer activity.}, } @article {pmid29038467, year = {2018}, author = {Bareia, T and Pollak, S and Eldar, A}, title = {Self-sensing in Bacillus subtilis quorum-sensing systems.}, journal = {Nature microbiology}, volume = {3}, number = {1}, pages = {83-89}, pmid = {29038467}, issn = {2058-5276}, mesh = {Ampicillin/pharmacology ; Anti-Bacterial Agents/pharmacology ; Bacillus subtilis/drug effects/genetics/metabolism/*physiology ; Bacterial Proteins/genetics/metabolism ; Coculture Techniques ; Drug Resistance, Bacterial/physiology ; Feedback, Physiological ; Gene Expression Regulation, Bacterial ; Mutation ; Quorum Sensing/genetics/*physiology ; *Signal Transduction ; }, abstract = {Bacterial cell-cell signalling, or quorum sensing, is characterized by the secretion and groupwide detection of small diffusible signal molecules called autoinducers. This mechanism allows cells to coordinate their behaviour in a density-dependent manner. A quorum-sensing cell may directly respond to the autoinducers it produces in a cell-autonomous and quorum-independent manner, but the strength of this self-sensing effect and its impact on bacterial physiology are unclear. Here, we explore the existence and impact of self-sensing in the Bacillus subtilis ComQXP and Rap-Phr quorum-sensing systems. By comparing the quorum-sensing response of autoinducer-secreting and non-secreting cells in co-culture, we find that secreting cells consistently show a stronger response than non-secreting cells. Combining genetic and quantitative analyses, we demonstrate this effect to be a direct result of self-sensing and rule out an indirect regulatory effect of the autoinducer production genes on response sensitivity. In addition, self-sensing in the ComQXP system affects persistence to antibiotic treatment. Together, these findings indicate the existence of self-sensing in the two most common designs of quorum-sensing systems of Gram-positive bacteria.}, } @article {pmid29038120, year = {2018}, author = {Germain, RN}, title = {Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? What Really Constitutes the Study of "Systems Biology" and How Might Such an Approach Facilitate Vaccine Design.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a033308}, pmid = {29038120}, issn = {1943-0264}, abstract = {A dichotomy exists in the field of vaccinology about the promise versus the hype associated with application of "systems biology" approaches to rational vaccine design. Some feel it is the only way to efficiently uncover currently unknown parameters controlling desired immune responses or discover what elements actually mediate these responses. Others feel that traditional experimental, often reductionist, methods for incrementally unraveling complex biology provide a more solid way forward, and that "systems" approaches are costly ways to collect data without gaining true insight. Here I argue that both views are inaccurate. This is largely because of confusion about what can be gained from classical experimentation versus statistical analysis of large data sets (bioinformatics) versus methods that quantitatively explain emergent properties of complex assemblies of biological components, with the latter reflecting what was previously called "physiology." Reductionist studies will remain essential for generating detailed insight into the functional attributes of specific elements of biological systems, but such analyses lack the power to provide a quantitative and predictive understanding of global system behavior. But by employing (1) large-scale screening methods for discovery of unknown components and connections in the immune system (omics), (2) statistical analysis of large data sets (bioinformatics), and (3) the capacity of quantitative computational methods to translate these individual components and connections into models of emergent behavior (systems biology), we will be able to better understand how the overall immune system functions and to determine with greater precision how to manipulate it to produce desired protective responses.}, } @article {pmid29038119, year = {2018}, author = {Davis, MM and Tato, CM}, title = {Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? Seeing the Forest Rather than a Few Trees.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, pmid = {29038119}, issn = {1943-0264}, support = {R37 AI022511/AI/NIAID NIH HHS/United States ; U19 AI057229/AI/NIAID NIH HHS/United States ; }, abstract = {Preventing morbidity and mortality from infectious disease through the development and use of effective vaccines is one of medicine's greatest achievements and greatest frustrations. We are struggling with improving vaccine efficacy for some of the most globally widespread diseases, such as malaria and tuberculosis. In an effort to gain an edge, systems biology approaches have begun to be employed to more broadly investigate the pathways leading to protective vaccine responses. As such, we are now at a critical juncture, needing to evaluate how fruitful these approaches have been. Herein we discuss the level of success achieved as compared to the original promise of systems methodologies, and conclude that while we have indeed begun to make clear inroads into understanding the immune response to vaccines, we still have much to learn and gain from the more comprehensive approach of systems-level analysis.}, } @article {pmid29038118, year = {2018}, author = {Kuhlman, SJ and Craig, LM and Duffy, JF}, title = {Introduction to Chronobiology.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a033613}, pmid = {29038118}, issn = {1943-0264}, abstract = {A diverse range of species, from cyanobacteria to humans, evolved endogenous biological clocks that allow for the anticipation of daily variations in light and temperature. The ability to anticipate regular environmental rhythms promotes optimal performance and survival. Herein we present a brief historical timeline of how circadian concepts and terminology have emerged since the early observation of daily leaf movement in plants made by an astronomer in the 1700s.}, } @article {pmid29038117, year = {2018}, author = {Rappuoli, R and Siena, E and Finco, O}, title = {Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? Systems Biology Views of Vaccine Innate and Adaptive Immunity.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a029256}, pmid = {29038117}, issn = {1943-0264}, abstract = {During the last decade, several high-throughput technologies have been applied to gather deeper understanding on the biological events elicited by vaccination. The main goal of systems biology is to integrate different sources of data and extract biologically meaningful information. This holistic approach has provided new insights on the impact that the innate immune status has on vaccine responsiveness. Other factors like chronic infections, age, microbiome, and metabolism can influence the outcome of vaccination, and systems biology offers unique opportunities to expand our understanding of their role on the immune response. However, a few challenges that still need to be overcome will be discussed.}, } @article {pmid29038116, year = {2018}, author = {Ode, KL and Ueda, HR}, title = {Design Principles of Phosphorylation-Dependent Timekeeping in Eukaryotic Circadian Clocks.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a028357}, pmid = {29038116}, issn = {1943-0264}, abstract = {The circadian clock in cyanobacteria employs a posttranslational oscillator composed of a sequential phosphorylation-dephosphorylation cycle of KaiC protein, in which the dynamics of protein structural changes driven by temperature-compensated KaiC's ATPase activity are critical for determining the period. On the other hand, circadian clocks in eukaryotes employ transcriptional feedback loops as a core mechanism. In this system, the dynamics of protein accumulation and degradation affect the circadian period. However, recent studies of eukaryotic circadian clocks reveal that the mechanism controlling the circadian period can be independent of the regulation of protein abundance. Instead, the circadian substrate is often phosphorylated at multiple sites at flexible protein regions to induce structural changes. The phosphorylation is catalyzed by kinases that induce sequential multisite phosphorylation such as casein kinase 1 (CK1) with temperature-compensated activity. We propose that the design principles of phosphorylation-dependent circadian-period determination in eukaryotes may share characteristics with the posttranslational oscillator in cyanobacteria.}, } @article {pmid29038115, year = {2018}, author = {Lin, JX and Leonard, WJ}, title = {The Common Cytokine Receptor γ Chain Family of Cytokines.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a028449}, pmid = {29038115}, issn = {1943-0264}, abstract = {Interleukin (IL)-2, IL-4, IL-7, IL-9, IL-15, and IL-21 form a family of cytokines based on their sharing the common cytokine receptor γ chain (γc), which was originally discovered as the third receptor component of the IL-2 receptor, IL-2Rγ. The IL2RG gene is located on the X chromosome and is mutated in humans with X-linked severe combined immunodeficiency (XSCID). The breadth of the defects in XSCID could not be explained solely by defects in IL-2 signaling, and it is now clear that γc is a shared receptor component of the six cytokines noted above, making XSCID a disease of defective cytokine signaling. Janus kinase (JAK)3 associates with γc, and JAK3-deficient SCID phenocopies XSCID, findings that served to stimulate the development of JAK3 inhibitors as immunosuppressants. γc family cytokines collectively control broad aspects of lymphocyte development, growth, differentiation, and survival, and these cytokines are clinically important, related to allergic and autoimmune diseases and cancer as well as immunodeficiency. In this review, we discuss the actions of these cytokines, their critical biological roles and signaling pathways, focusing mainly on JAK/STAT (signal transducers and activators of transcription) signaling, and how this information is now being used in clinical therapeutic efforts.}, } @article {pmid29038113, year = {2018}, author = {Hagan, T and Pulendran, B}, title = {Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines? From Data to Understanding through Systems Biology.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, pmid = {29038113}, issn = {1943-0264}, support = {R37 AI048638/AI/NIAID NIH HHS/United States ; R37 DK057665/DK/NIDDK NIH HHS/United States ; U19 AI057266/AI/NIAID NIH HHS/United States ; U19 AI090023/AI/NIAID NIH HHS/United States ; }, abstract = {The advent of high-throughput "omics" technologies, combined with the computational and statistical methods necessary to analyze such data, have revolutionized biology, enabling a global view of the complex molecular processes and interactions that occur within a biological system. Such systems-based approaches have begun to be used in the evaluation of immune responses to vaccination, with the promise of identifying predictive biomarkers capable of rapidly evaluating vaccine efficacy, transforming our understanding of the immune mechanisms responsible for protective responses to vaccination and contributing to a new generation of rationally designed vaccines. Here we present our opinion that systems biology does indeed have a critical role in the future of vaccinology. Such approaches have shown potential in identifying transcriptional and cellular signatures of responsiveness to vaccination using diverse vaccines, adjuvants, and human populations. These findings, coupled with further mechanistic evaluation in animal models, will guide development of targeted vaccine and adjuvant formulations designed to optimally induce protective responses in populations of differing immune status.}, } @article {pmid29038112, year = {2018}, author = {Tognini, P and Murakami, M and Sassone-Corsi, P}, title = {Interplay between Microbes and the Circadian Clock.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a028365}, pmid = {29038112}, issn = {1943-0264}, abstract = {Circadian rhythms influence virtually all life forms on our planet, a notion that opens the question on how the circadian cycles of individual organisms may interplay with each other. In mammals, a potentially dangerous environmental stress is represented by encounters with infectious agents. Microbial attack is a major risk for organismal homeostasis and therefore needs to be efficiently counteracted by mechanisms implemented by the host immune system. Accumulating evidence shows that the immune system may anticipate an emerging pathogenic exposure through an enhanced inflammatory state. Notably, the circadian clock orchestrates these anticipatory responses to fluctuating conditions in the external world. In this article, we review the current knowledge about the relationship between the circadian clock and pathogenic infections. We discuss the role of the circadian clock against infection and specific pathogens, the core clock proteins involved in the defense mechanisms, and the specific tissue or cell type in which they function to counteract the infection. Finally, circadian oscillations in the gut microbiome composition and its possible role in protecting against foodborne pathogen colonization are presented.}, } @article {pmid29038046, year = {2018}, author = {Sun, S and Li, Q and Kong, L and Yu, H}, title = {Multiple reversals of strand asymmetry in molluscs mitochondrial genomes, and consequences for phylogenetic inferences.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {222-231}, doi = {10.1016/j.ympev.2017.10.009}, pmid = {29038046}, issn = {1095-9513}, mesh = {Amino Acids/chemistry/metabolism ; Animals ; Base Composition ; Bivalvia/classification/genetics ; Codon ; Gastropoda/classification/genetics ; *Genome, Mitochondrial ; Mollusca/*classification/genetics ; Phylogeny ; }, abstract = {Strand asymmetry in nucleotide composition is a remarkable feature of animal mitochondrial genomes. The strand-specific bias in the nucleotide composition of the mtDNA has been known to be highly problematic for phylogenetic analyses. Here, the strand asymmetry was compared across 140 mollusc species and analyzed for a mtDNA fragment including twelve protein-coding genes. The analyses show that almost all species in Gastropoda (except Heterobranchia) and all species in Bivalvia present reversals of strand bias. The skew values on individual genes for all codon positions (P123), third codon positions (P3), and fourfold redundant third codon positions (P4FD) indicated that CG skews are the best indicators of strand asymmetry. The differences in the patterns of strand asymmetry significantly influenced the amino acid composition of the encoded proteins. These biases are most striking for the amino acids Valine, Cysteine, Asparagine and Threonines, which appear to have evolved asymmetrical exchanges in response to shifts in nucleotide composition. Molluscs with strong variability of genome architectures (ARs) are usually characterized by a reversal of the usual strand bias. Phylogenetic analyses show that reversals of asymmetric mutational constraints have consequences on the phylogenetic inferences, as taxa characterized by reverse strand bias (Heterobranchia and Bivalvia) tend to group together due to long-branch attraction (LBA) artifacts. Neutral Transitions Excluded (NTE) model did not overcome the problem of heterogeneous biases present in molluscs mt genomes, suggested it may not be appropriate for molluscs mt genome data. Further refinement phylogenetic models may help us better understand internal relationships among these diverse organisms.}, } @article {pmid29037439, year = {2018}, author = {Albritton, SE and Ercan, S}, title = {Caenorhabditis elegans Dosage Compensation: Insights into Condensin-Mediated Gene Regulation.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {41-53}, pmid = {29037439}, issn = {0168-9525}, support = {R01 GM107293/GM/NIGMS NIH HHS/United States ; }, mesh = {Adenosine Triphosphatases/*genetics ; Animals ; Caenorhabditis elegans/*genetics ; DNA-Binding Proteins/*genetics ; *Dosage Compensation, Genetic ; Female ; Gene Expression Regulation ; Multiprotein Complexes/*genetics ; X Chromosome ; }, abstract = {Recent work demonstrating the role of chromosome organization in transcriptional regulation has sparked substantial interest in the molecular mechanisms that control chromosome structure. Condensin, an evolutionarily conserved multisubunit protein complex, is essential for chromosome condensation during cell division and functions in regulating gene expression during interphase. In Caenorhabditis elegans, a specialized condensin forms the core of the dosage compensation complex (DCC), which specifically binds to and represses transcription from the hermaphrodite X chromosomes. DCC serves as a clear paradigm for addressing how condensins target large chromosomal domains and how they function to regulate chromosome structure and transcription. Here, we discuss recent research on C. elegans DCC in the context of canonical condensin mechanisms as have been studied in various organisms.}, } @article {pmid29037438, year = {2018}, author = {Weaver, BP and Han, M}, title = {Tag team: Roles of miRNAs and Proteolytic Regulators in Ensuring Robust Gene Expression Dynamics.}, journal = {Trends in genetics : TIG}, volume = {34}, number = {1}, pages = {21-29}, pmid = {29037438}, issn = {0168-9525}, support = {R01 GM047869/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, mesh = {Animals ; Caenorhabditis elegans Proteins/genetics ; Caspases/genetics ; *Gene Expression ; Gene Regulatory Networks ; MicroRNAs/*genetics ; Proteolysis ; Repressor Proteins/genetics ; }, abstract = {Lack of prominent developmental defects arising from loss of many individual miRNAs is consistent with the observations of collaborative networks between miRNAs and roles for miRNAs in regulating stress responses. However, these characteristics may only partially explain the seemingly nonessential nature of many miRNAs. Non-miRNA gene expression regulatory mechanisms also collaborate with miRNA-induced silencing complex (miRISC) to support robust gene expression dynamics. Genetic enhancer screens have revealed roles of miRNAs and other gene repressive mechanisms in development or other cellular processes that were masked by genetic redundancy. Besides discussing the breadth of the non-miRNA genes, we use LIN-28 as an example to illustrate how distinct regulatory systems, including miRNAs and multiple protein stability mechanisms, work at different levels to target expression of a given gene and provide tissue-specific and stage-specific regulation of gene expression.}, } @article {pmid29036491, year = {2018}, author = {Bergman, J and Betancourt, AJ and Vogl, C}, title = {Transcription-Associated Compositional Skews in Drosophila Genes.}, journal = {Genome biology and evolution}, volume = {10}, number = {1}, pages = {269-275}, pmid = {29036491}, issn = {1759-6653}, mesh = {Animals ; Base Composition ; Drosophila melanogaster/*genetics ; *Evolution, Molecular ; *Genes, Insect ; Mutation Accumulation ; *Transcription, Genetic ; }, abstract = {In many organisms, local deviations from Chargaff's second parity rule are observed around replication and transcription start sites and within intron sequences. Here, we use expression data as well as a whole-genome data set of nearly 200 haplotypes to investigate such compositional skews in Drosophila melanogaster genes. We find a positive correlation between compositional skew and gene expression, comparable in strength to similar correlations between expression levels and genome-wide sequence features. This correlation is relatively stronger for germline, compared with somatic expression, consistent with the process of transcription-associated mutation bias. We also inferred mutation rates from alleles segregating at low frequencies in short introns, and show that, whereas the overall GC content of short introns does not conform to the equilibrium expectation, the level of the observed deviation from the second parity rule is generally consistent with the inferred rates.}, } @article {pmid29034568, year = {2018}, author = {Wood, R and Erwin, DH}, title = {Innovation not recovery: dynamic redox promotes metazoan radiations.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {863-873}, doi = {10.1111/brv.12375}, pmid = {29034568}, issn = {1469-185X}, abstract = {Environmental fluctuations in redox may reinforce rather than hinder evolutionary transitions, such that variability in near-surface oceanic oxygenation can promote morphological evolution and novelty. Modern, low-oxygen regions are heterogeneous and dynamic habitats that support low diversity and are inhabited by opportunistic and non-skeletal metazoans. We note that several major radiation episodes follow protracted or repeating intervals (>1 million years) of persistent and dynamic shallow marine redox (oceanic anoxic events). These are also often associated with short-lived mass-extinction events (<0.5 million years) where skeletal benthic incumbents are removed, and surviving or newly evolved benthos initially inhabit transient oxic habitats. We argue that such intervals create critical opportunities for the generation of evolutionary novelty, followed by innovation and diversification. We develop a general model for redox controls on the distribution and structure of the shallow marine benthos in a dominantly anoxic world, and compile data from the terminal Ediacaran-mid-Cambrian (∼560-509 Ma), late Cambrian-Ordovician (∼500-445 Ma), and Permo-Triassic (∼255-205 Ma) to test these predictions. Assembly of phylogenetic data shows that prolonged and widespread anoxic intervals indeed promoted morphological novelty in soft-bodied benthos, providing the ancestral stock for subsequently skeletonized lineages to appear as innovations once oxic conditions became widespread and stable, in turn promoting major evolutionary diversification. As a result, we propose that so-called 'recovery' intervals after mass extinctions might be better considered as 'innovation' intervals.}, } @article {pmid29033457, year = {2018}, author = {Rancati, G and Moffat, J and Typas, A and Pavelka, N}, title = {Emerging and evolving concepts in gene essentiality.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {1}, pages = {34-49}, pmid = {29033457}, issn = {1471-0064}, mesh = {Animals ; Conserved Sequence ; Drug Delivery Systems ; Drug Resistance/genetics ; Evolution, Molecular ; Gene Editing ; Gene Regulatory Networks ; *Genes, Essential ; Genomics ; High-Throughput Nucleotide Sequencing ; Humans ; Metabolic Engineering ; Models, Genetic ; Synthetic Biology ; }, abstract = {Gene essentiality is a founding concept of genetics with important implications in both fundamental and applied research. Multiple screens have been performed over the years in bacteria, yeasts, animals and more recently in human cells to identify essential genes. A mounting body of evidence suggests that gene essentiality, rather than being a static and binary property, is both context dependent and evolvable in all kingdoms of life. This concept of a non-absolute nature of gene essentiality changes our fundamental understanding of essential biological processes and could directly affect future treatment strategies for cancer and infectious diseases.}, } @article {pmid29033456, year = {2018}, author = {Lyko, F}, title = {The DNA methyltransferase family: a versatile toolkit for epigenetic regulation.}, journal = {Nature reviews. Genetics}, volume = {19}, number = {2}, pages = {81-92}, pmid = {29033456}, issn = {1471-0064}, abstract = {The DNA methyltransferase (DNMT) family comprises a conserved set of DNA-modifying enzymes that have a central role in epigenetic gene regulation. Recent studies have shown that the functions of the canonical DNMT enzymes - DNMT1, DNMT3A and DNMT3B - go beyond their traditional roles of establishing and maintaining DNA methylation patterns. This Review analyses how molecular interactions and changes in gene copy numbers modulate the activity of DNMTs in diverse gene regulatory functions, including transcriptional silencing, transcriptional activation and post-transcriptional regulation by DNMT2-dependent tRNA methylation. This mechanistic diversity enables the DNMT family to function as a versatile toolkit for epigenetic regulation.}, } @article {pmid29033339, year = {2018}, author = {Bull, JJ and Smithson, MW and Nuismer, SL}, title = {Transmissible Viral Vaccines.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {6-15}, pmid = {29033339}, issn = {1878-4380}, support = {R01 GM122079/GM/NIGMS NIH HHS/United States ; }, mesh = {Communicable Disease Control ; Cross Reactions/immunology ; Disease Eradication/*methods ; Epidemiology ; Genetic Engineering ; Humans ; Immunity, Herd ; Models, Theoretical ; *Vaccination ; Vaccines, Attenuated/genetics/*immunology/therapeutic use ; Vaccines, Synthetic ; Viral Vaccines/genetics/*immunology/therapeutic use ; Viruses/genetics/immunology ; }, abstract = {Genetic engineering now enables the design of live viral vaccines that are potentially transmissible. Some designs merely modify a single viral genome to improve on the age-old method of attenuation whereas other designs create chimeras of viral genomes. Transmission has the benefit of increasing herd immunity above that achieved by direct vaccination alone but also increases the opportunity for vaccine evolution, which typically undermines vaccine utility. Different designs have different epidemiological consequences but also experience different evolution. Approaches that integrate vaccine engineering with an understanding of evolution and epidemiology will reap the greatest benefit from vaccine transmission.}, } @article {pmid29033338, year = {2018}, author = {Karkman, A and Do, TT and Walsh, F and Virta, MPJ}, title = {Antibiotic-Resistance Genes in Waste Water.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {220-228}, doi = {10.1016/j.tim.2017.09.005}, pmid = {29033338}, issn = {1878-4380}, mesh = {Anti-Bacterial Agents/pharmacology ; Disinfectants/pharmacology ; Drug Resistance, Microbial/*genetics ; *Gene Transfer, Horizontal ; Metagenomics/methods ; Metals ; Polymerase Chain Reaction/methods ; Sewage/microbiology ; Waste Water/*microbiology ; }, abstract = {Waste water and waste water treatment plants can act as reservoirs and environmental suppliers of antibiotic resistance. They have also been proposed to be hotspots for horizontal gene transfer, enabling the spread of antibiotic resistance genes between different bacterial species. Waste water contains antibiotics, disinfectants, and metals which can form a selection pressure for antibiotic resistance, even in low concentrations. Our knowledge of antibiotic resistance in waste water has increased tremendously in the past few years with advances in the molecular methods available. However, there are still some gaps in our knowledge on the subject, such as how active is horizontal gene transfer in waste water and what is the role of the waste water treatment plant in the environmental resistome? The purpose of this review is to briefly describe some of the main methods for studying antibiotic resistance in waste waters and the latest research and main knowledge gaps on the issue. In addition, some future research directions are proposed.}, } @article {pmid29032900, year = {2018}, author = {Klingen, TR and Reimering, S and Guzmán, CA and McHardy, AC}, title = {In Silico Vaccine Strain Prediction for Human Influenza Viruses.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {119-131}, doi = {10.1016/j.tim.2017.09.001}, pmid = {29032900}, issn = {1878-4380}, mesh = {Antibodies, Viral/immunology ; Antigens, Viral/immunology ; Biological Evolution ; *Computational Biology ; Forecasting ; Global Health ; Humans ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza Vaccines/*immunology ; Influenza, Human/epidemiology/*prevention & control/virology ; Orthomyxoviridae/immunology ; Seasons ; Vaccination/methods ; World Health Organization ; }, abstract = {Vaccines preventing seasonal influenza infections save many lives every year; however, due to rapid viral evolution, they have to be updated frequently to remain effective. To identify appropriate vaccine strains, the World Health Organization (WHO) operates a global program that continually generates and interprets surveillance data. Over the past decade, sophisticated computational techniques, drawing from multiple theoretical disciplines, have been developed that predict viral lineages rising to predominance, assess their suitability as vaccine strains, link genetic to antigenic alterations, as well as integrate and visualize genetic, epidemiological, structural, and antigenic data. These could form the basis of an objective and reproducible vaccine strain-selection procedure utilizing the complex, large-scale data types from surveillance. To this end, computational techniques should already be incorporated into the vaccine-selection process in an independent, parallel track, and their performance continuously evaluated.}, } @article {pmid29032467, year = {2018}, author = {Linn, AK and Samainukul, N and Sakdee, S and Angsuthanasombat, C and Katzenmeier, G}, title = {A Helicobacter pylori Vacuolating Cytotoxin A: Mouse DHFR Fusion Protein Triggers Dye Release from Liposomes.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {223-230}, pmid = {29032467}, issn = {1432-0991}, support = {RSA5580047//Thailand Research Fund/ ; }, mesh = {Animals ; Bacterial Proteins/genetics/*metabolism ; Coloring Agents/*metabolism ; Escherichia coli/genetics/metabolism ; Gene Expression ; Liposomes/*metabolism ; Membranes/metabolism ; Mice ; Recombinant Fusion Proteins/genetics/*metabolism ; Tetrahydrofolate Dehydrogenase/genetics/*metabolism ; }, abstract = {The membrane perturbing action of the VacA toxin from Helicobacter pylori is responsible for vacuole formation in intracellular compartments and the induction of apoptosis. The VacA toxin contains 2 major domains, p33 and p55, which are involved in receptor binding and membrane pore formation, respectively. Improved methodologies for VacA purification and assays are urgently needed for further detailed investigations on the mechanism of action of this significant virulence factor. We found that by fusing mouse DHFR with the N-terminus of the full-length (p88) VacA toxin, expression levels in recombinant E. coli were substantially increased when compared to the conventional (His)6-tagged protein. The DHFR-VacA fusion protein was active in sulforhodamine dye-release assays using liposomes at acidic pH in a concentration-dependent manner. Enzymatic activity of DHFR in the fusion protein was comparable to a commercial reference sample of purified DHFR; however, activity was insensitive to inhibition by methotrexate. Our findings suggest that the VacA p88 toxin with a modified N-terminus still maintains its capability for membrane insertion and that pH-dependent conformational changes occur during interaction of VacA with membranes.}, } @article {pmid29031585, year = {2018}, author = {Ilves, KL and Torti, D and López-Fernández, H}, title = {Exon-based phylogenomics strengthens the phylogeny of Neotropical cichlids and identifies remaining conflicting clades (Cichliformes: Cichlidae: Cichlinae).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {232-243}, doi = {10.1016/j.ympev.2017.10.008}, pmid = {29031585}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Biological Evolution ; Cichlids/*classification/genetics ; DNA/chemistry/isolation & purification/metabolism ; Exons ; High-Throughput Nucleotide Sequencing ; Phylogeny ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The phenotypic, geographic, and species diversity of cichlid fishes have made them a group of great interest for studying evolutionary processes. Here we present a targeted-exon next-generation sequencing approach for investigating the evolutionary relationships of cichlid fishes (Cichlidae), with focus on the Neotropical subfamily Cichlinae using a set of 923 primarily single-copy exons designed through mining of the Nile tilapia (Oreochromis niloticus) genome. Sequence capture and assembly were robust, leading to a complete dataset of 415 exons for 139 species (147 terminals) that consisted of 128 Neotropical species, six African taxa, and five Indo-Malagasy cichlids. Gene and species trees were calculated using alternative partitioning schemes and reconstruction methods. In general, all methods yielded similar topologies to previously hypothesized relationships within the Cichlinae and clarified several relationships that were previously poorly supported or in conflict. Additional work will be needed to fully resolve all aspects of Cichlinae phylogeny. Overall, this approach yielded a well-resolved phylogeny of Neotropical cichlids that will be of utility for future assessments of the evolutionary and ecological processes within this diverse group of fishes. Furthermore, the general methodology employed here of exon targeting and capture should be applicable to any group of organisms with the availability of a reference genome.}, } @article {pmid29031509, year = {2018}, author = {Bennuru, S and O'Connell, EM and Drame, PM and Nutman, TB}, title = {Mining Filarial Genomes for Diagnostic and Therapeutic Targets.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {80-90}, pmid = {29031509}, issn = {1471-5007}, support = {ZIA AI000512-29//NULL/International ; }, mesh = {Animals ; Data Mining ; Drug Delivery Systems/*trends ; Filariasis/diagnosis/drug therapy/parasitology/*prevention & control ; Filaricides/standards/therapeutic use ; Genome, Helminth/*genetics ; Humans ; Nematoda/drug effects/*genetics ; }, abstract = {Filarial infections of humans cause some of the most important neglected tropical diseases. The global efforts for eliminating filarial infections by mass drug administration programs may require additional tools (safe macrofilaricidal drugs, vaccines, and diagnostic biomarkers). The accurate and sensitive detection of viable parasites is essential for diagnosis and for surveillance programs. Current community-wide treatment modalities do not kill the adult filarial worms effectively; hence, there is a need to identify and develop safe macrofilaricidal drugs. High-throughput sequencing, mass spectroscopy methods and advances in computational biology have greatly accelerated the discovery process. Here, we describe post-genomic developments toward the identification of diagnostic biomarkers and drug targets for the filarial infection of humans.}, } @article {pmid29030895, year = {2018}, author = {Brown, KE and Kelly, JK}, title = {Antagonistic pleiotropy can maintain fitness variation in annual plants.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {46-56}, doi = {10.1111/jeb.13192}, pmid = {29030895}, issn = {1420-9101}, support = {R01 GM073990/GM/NIGMS NIH HHS/United States ; }, mesh = {Genetic Fitness/*physiology ; *Genetic Pleiotropy ; Mimulus/genetics/*physiology ; *Models, Biological ; }, abstract = {Antagonistic pleiotropy (AP) is a genetic trade-off between different fitness components. In annual plants, a trade-off between days to flower (DTF) and reproductive capacity often determines how many individuals survive to flower in a short growing season, and also influences the seed set of survivors. We develop a model of viability and fecundity selection informed by many experiments on the yellow monkeyflower, Mimulus guttatus, but applicable to many annual species. A viability/fecundity trade-off maintains stable polymorphism under surprisingly general conditions. We also introduce both spatial heterogeneity and temporal stochasticity in environmental parameters. Neither is necessary for polymorphism, but spatial heterogeneity allows polymorphism while also generating the often observed non-negative correlations in fitness components.}, } @article {pmid29029809, year = {2018}, author = {Naito, YI and Chikaraishi, Y and Drucker, DG and Ohkouchi, N and Semal, P and Wißing, C and Bocherens, H}, title = {Reply to "Comment on "Ecological niche of Neanderthals from Spy Cave revealed by nitrogen isotopes of individual amino acids in collagen." [J. Hum. Evol. 93 (2016) 82-90]" [J. Hum. Evol. 117 (2018) 53-55].}, journal = {Journal of human evolution}, volume = {117}, number = {}, pages = {56-60}, doi = {10.1016/j.jhevol.2017.09.008}, pmid = {29029809}, issn = {1095-8606}, } @article {pmid29029576, year = {2018}, author = {Brooks, SD and Thornton, DCO}, title = {Marine Aerosols and Clouds.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {289-313}, doi = {10.1146/annurev-marine-121916-063148}, pmid = {29029576}, issn = {1941-0611}, abstract = {The role of marine bioaerosols in cloud formation and climate is currently so uncertain that even the sign of the climate forcing is unclear. Marine aerosols form through direct emissions and through the conversion of gas-phase emissions to aerosols in the atmosphere. The composition and size of aerosols determine how effective they are in catalyzing the formation of water droplets and ice crystals in clouds by acting as cloud condensation nuclei and ice nucleating particles, respectively. Marine organic aerosols may be sourced both from recent regional phytoplankton blooms that add labile organic matter to the surface ocean and from long-term global processes, such as the upwelling of old refractory dissolved organic matter from the deep ocean. Understanding the formation of marine aerosols and their propensity to catalyze cloud formation processes are challenges that must be addressed given the major uncertainties associated with aerosols in climate models.}, } @article {pmid29029269, year = {2018}, author = {Wang, J and Sun, P and Li, Y and Liu, Y and Yang, N and Yu, J and Ma, X and Sun, S and Xia, R and Liu, X and Ge, D and Luo, S and Liu, Y and Kong, Y and Cui, X and Lei, T and Wang, L and Wang, Z and Ge, W and Zhang, L and Song, X and Yuan, M and Guo, D and Jin, D and Chen, W and Pan, Y and Liu, T and Yang, G and Xiao, Y and Sun, J and Zhang, C and Li, Z and Xu, H and Duan, X and Shen, S and Zhang, Z and Huang, S and Wang, X}, title = {An Overlooked Paleotetraploidization in Cucurbitaceae.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {16-26}, pmid = {29029269}, issn = {1537-1719}, abstract = {Cucurbitaceae plants are of considerable biological and economic importance, and genomes of cucumber, watermelon, and melon have been sequenced. However, a comparative genomics exploration of their genome structures and evolution has not been available. Here, we aimed at performing a hierarchical inference of genomic homology resulted from recursive paleopolyploidizations. Unexpectedly, we found that, shortly after a core-eudicot-common hexaploidy, a cucurbit-common tetraploidization (CCT) occurred, overlooked by previous reports. Moreover, we characterized gene loss (and retention) after these respective events, which were significantly unbalanced between inferred subgenomes, and between plants after their split. The inference of a dominant subgenome and a sensitive one suggested an allotetraploid nature of the CCT. Besides, we found divergent evolutionary rates among cucurbits, and after doing rate correction, we dated the CCT to be 90-102 Ma, likely common to all Cucurbitaceae plants, showing its important role in the establishment of the plant family.}, } @article {pmid29029259, year = {2018}, author = {Charon, J and Barra, A and Walter, J and Millot, P and Hébrard, E and Moury, B and Michon, T}, title = {First Experimental Assessment of Protein Intrinsic Disorder Involvement in an RNA Virus Natural Adaptive Process.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {38-49}, pmid = {29029259}, issn = {1537-1719}, abstract = {Intrinsic disorder (ID) in proteins is defined as a lack of stable structure in physiological conditions. Intrinsically disordered regions (IDRs) are highly abundant in some RNA virus proteomes. Low topological constraints exerted on IDRs are expected to buffer the effect of numerous deleterious mutations and could be related to the remarkable adaptive potential of RNA viruses to overcome resistance of their host. To experimentally test this hypothesis in a natural pathosystem, a set of four variants of Potato virus Y (PVY; Potyvirus genus) containing various ID degrees in the Viral genome-linked (VPg) protein, a key determinant of potyvirus adaptation, was designed. To estimate the ID contribution to the VPg-based PVY adaptation, the adaptive ability of the four PVY variants was monitored in the pepper host (Capsicum annuum) carrying a recessive resistance gene. Intriguingly, the two mutants with the highest ID content displayed a significantly higher ability to restore infection in the resistant host, whereas the less intrinsically disordered mutant was unable to restore infection. The role of ID on virus adaptation may be due either to a larger exploration of evolutionary pathways or the minimization of fitness penalty caused by resistance-breaking mutations. This pioneering study strongly suggests the positive impact of ID in an RNA virus adaptive capacity.}, } @article {pmid29029206, year = {2018}, author = {Bertels, F and Marzel, A and Leventhal, G and Mitov, V and Fellay, J and Günthard, HF and Böni, J and Yerly, S and Klimkait, T and Aubert, V and Battegay, M and Rauch, A and Cavassini, M and Calmy, A and Bernasconi, E and Schmid, P and Scherrer, AU and Müller, V and Bonhoeffer, S and Kouyos, R and Regoes, RR and , }, title = {Dissecting HIV Virulence: Heritability of Setpoint Viral Load, CD4+ T-Cell Decline, and Per-Parasite Pathogenicity.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {27-37}, pmid = {29029206}, issn = {1537-1719}, abstract = {Pathogen strains may differ in virulence because they attain different loads in their hosts, or because they induce different disease-causing mechanisms independent of their load. In evolutionary ecology, the latter is referred to as "per-parasite pathogenicity". Using viral load and CD4+ T-cell measures from 2014 HIV-1 subtype B-infected individuals enrolled in the Swiss HIV Cohort Study, we investigated if virulence-measured as the rate of decline of CD4+ T cells-and per-parasite pathogenicity are heritable from donor to recipient. We estimated heritability by donor-recipient regressions applied to 196 previously identified transmission pairs, and by phylogenetic mixed models applied to a phylogenetic tree inferred from HIV pol sequences. Regressing the CD4+ T-cell declines and per-parasite pathogenicities of the transmission pairs did not yield heritability estimates significantly different from zero. With the phylogenetic mixed model, however, our best estimate for the heritability of the CD4+ T-cell decline is 17% (5-30%), and that of the per-parasite pathogenicity is 17% (4-29%). Further, we confirm that the set-point viral load is heritable, and estimate a heritability of 29% (12-46%). Interestingly, the pattern of evolution of all these traits differs significantly from neutrality, and is most consistent with stabilizing selection for the set-point viral load, and with directional selection for the CD4+ T-cell decline and the per-parasite pathogenicity. Our analysis shows that the viral genotype affects virulence mainly by modulating the per-parasite pathogenicity, while the indirect effect via the set-point viral load is minor.}, } @article {pmid29029199, year = {2018}, author = {Claywell, BC and Dinh, V and Fourment, M and McCoy, CO and Matsen Iv, FA}, title = {A Surrogate Function for One-Dimensional Phylogenetic Likelihoods.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {242-246}, pmid = {29029199}, issn = {1537-1719}, support = {U54 GM111274/GM/NIGMS NIH HHS/United States ; /HHMI/Howard Hughes Medical Institute/United States ; }, abstract = {Phylogenetics has seen a steady increase in data set size and substitution model complexity, which require increasing amounts of computational power to compute likelihoods. This motivates strategies to approximate the likelihood functions for branch length optimization and Bayesian sampling. In this article, we develop an approximation to the 1D likelihood function as parametrized by a single branch length. Our method uses a four-parameter surrogate function abstracted from the simplest phylogenetic likelihood function, the binary symmetric model. We show that it offers a surrogate that can be fit over a variety of branch lengths, that it is applicable to a wide variety of models and trees, and that it can be used effectively as a proposal mechanism for Bayesian sampling. The method is implemented as a stand-alone open-source C library for calling from phylogenetics algorithms; it has proven essential for good performance of our online phylogenetic algorithm sts.}, } @article {pmid29029186, year = {2018}, author = {Lam, HM and Ratmann, O and Boni, MF}, title = {Improved Algorithmic Complexity for the 3SEQ Recombination Detection Algorithm.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {247-251}, pmid = {29029186}, issn = {1537-1719}, support = {//Wellcome Trust/United Kingdom ; 089276/B/09/7//Wellcome Trust/United Kingdom ; 098511/Z/12/Z//Wellcome Trust/United Kingdom ; }, abstract = {Identifying recombinant sequences in an era of large genomic databases is challenging as it requires an efficient algorithm to identify candidate recombinants and parents, as well as appropriate statistical methods to correct for the large number of comparisons performed. In 2007, a computation was introduced for an exact nonparametric mosaicism statistic that gave high-precision P values for putative recombinants. This exact computation meant that multiple-comparisons corrected P values also had high precision, which is crucial when performing millions or billions of tests in large databases. Here, we introduce an improvement to the algorithmic complexity of this computation from O(mn3) to O(mn2), where m and n are the numbers of recombination-informative sites in the candidate recombinant. This new computation allows for recombination analysis to be performed in alignments with thousands of polymorphic sites. Benchmark runs are presented on viral genome sequence alignments, new features are introduced, and applications outside recombination analysis are discussed.}, } @article {pmid29027742, year = {2018}, author = {Mera, H and Bourne, DG}, title = {Disentangling causation: complex roles of coral-associated microorganisms in disease.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {431-449}, doi = {10.1111/1462-2920.13958}, pmid = {29027742}, issn = {1462-2920}, abstract = {Rapidly changing climate regimes combined with other anthropogenic pressures are implicated in increased disease epizootics among reef building corals, resulting in changing habitat structure. These accumulated stressors directly contribute to disease outbreaks by compromising the coral host immune system, modulating virulence of microbial pathogens and/or disrupting the balance within the microbiome of the holobiont. Disentangling coral disease causation has been challenging, and while progress has been made for certain diseases in terms of the roles the associated microorganisms play, it is evident that like in other marine or terrestrial systems, compromised host health cannot always be attributed to a single causative agent. Here, we summarize the current state in knowledge of microbial induced coral diseases, and discuss challenges and strategies to further disentangle disease causation. With the major environmental pressures coral reefs face over the next century, understanding interactions between host, environmental and microbial causative agent(s) that lead to disease, is still a priority to enable development of effective strategies for building resilience into coral populations.}, } @article {pmid29027582, year = {2018}, author = {Kumar, A and Saini, HS and Kumar, S}, title = {Bioleaching of Gold and Silver from Waste Printed Circuit Boards by Pseudomonas balearica SAE1 Isolated from an e-Waste Recycling Facility.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {194-201}, pmid = {29027582}, issn = {1432-0991}, support = {BT/PR7478/BCE/8/951/2013//Department of Biotechnology, Ministry of Science and Technology/ ; }, mesh = {Culture Media/chemistry ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; *Environmental Microbiology ; Gold/*metabolism ; Hydrogen-Ion Concentration ; India ; *Industrial Waste ; Pseudomonas/classification/genetics/*isolation & purification/*metabolism ; RNA, Ribosomal, 16S/genetics ; Recycling ; Sequence Analysis, DNA ; Silver/*metabolism ; Temperature ; }, abstract = {Indigenous bacterial strain Pseudomonas balearica SAE1, tolerant to e-waste toxicity was isolated from an e-waste recycling facility Exigo Recycling Pvt. Ltd., India. Toxicity tolerance of bacterial strain was analyzed using crushed (particle size ≤150 µm) waste computer printed circuit boards (PCBs)/liter (L) of culture medium. The EC50 value for SAE1 was 325.7 g/L of the e-waste pulp density. Two-step bioleaching was then applied to achieve the dissolution of gold (Au) and silver (Ag) from the e-waste. To maximize precious metal dissolution, factors including pulp density, glycine concentration, pH level, and temperature were optimized. The optimization resulted in 68.5 and 33.8% of Au and Ag dissolution, respectively, at a pH of 9.0, a pulp density of 10 g/L, a temperature of 30 °C, and a glycine concentration of 5 g/L. This is the first study of Au and Ag bioleaching using indigenous e-waste bacteria and its analysis to determine e-waste toxicity tolerance.}, } @article {pmid29027375, year = {2018}, author = {Baker-Austin, C and Oliver, JD}, title = {Vibrio vulnificus: new insights into a deadly opportunistic pathogen.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {423-430}, doi = {10.1111/1462-2920.13955}, pmid = {29027375}, issn = {1462-2920}, abstract = {Vibrio vulnificus is a Gram-negative aquatic bacterium first isolated by the United States (US) Centers for Disease Control and Prevention (CDC) in 1964. This bacterium is part of the normal microbiota of estuarine waters and occurs in high numbers in molluscan shellfish around the world, particularly in warmer months. Infections in humans are derived from consumption of seafood produce and from water exposure. Vibrio vulnificus is a striking and enigmatic human pathogen, yet many aspects related to its biology, genomics, virulence capabilities and epidemiology remain elusive and poorly understood. This pathogen is responsible for over 95% of seafood-related deaths in the United States, and carries the highest fatality rate of any food-borne pathogen. Indeed, infections associated with this pathogen that progress to primary septicaemia have a similar case fatality rate to category BSL 3 and 4 pathogens, such as anthrax, bubonic plague, Ebola and Marburg fever. Interestingly, V. vulnificus infections disproportionately affect males (∼85% of cases) and older patients (> 40 years), especially those with underlying conditions such as liver diseases, diabetes and immune disorders. New insights from molecular studies and comparative genomic approaches have offered tantalising insights into this pathogen. A recent increase and geographical spread in reported infections, in particular wound cases, underlines the growing international importance of V. vulnificus, particularly in the context of coastal warming. We outline and explore here a range of current data gaps regarding this important pathogen, and provide some current thoughts on approaches to elucidate key aspects associated with this bacterium.}, } @article {pmid29027374, year = {2018}, author = {Props, R and Schmidt, ML and Heyse, J and Vanderploeg, HA and Boon, N and Denef, VJ}, title = {Flow cytometric monitoring of bacterioplankton phenotypic diversity predicts high population-specific feeding rates by invasive dreissenid mussels.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {521-534}, doi = {10.1111/1462-2920.13953}, pmid = {29027374}, issn = {1462-2920}, abstract = {Species invasion is an important disturbance to ecosystems worldwide, yet knowledge about the impacts of invasive species on bacterial communities remains sparse. Using a novel approach, we simultaneously detected phenotypic and derived taxonomic change in a natural bacterioplankton community when subjected to feeding pressure by quagga mussels, a widespread aquatic invasive species. We detected a significant decrease in diversity within 1 h of feeding and a total diversity loss of 11.6 ± 4.1% after 3 h. This loss of microbial diversity was caused by the selective removal of high nucleic acid populations (29 ± 5% after 3 h). We were able to track the community diversity at high temporal resolution by calculating phenotypic diversity estimates from flow cytometry (FCM) data of minute amounts of sample. Through parallel FCM and 16S rRNA gene amplicon sequencing analysis of environments spanning a broad diversity range, we showed that the two approaches resulted in highly correlated diversity measures and captured the same seasonal and lake-specific patterns in community composition. Based on our results, we predict that selective feeding by invasive dreissenid mussels directly impacts the microbial component of the carbon cycle, as it may drive bacterioplankton communities toward less diverse and potentially less productive states.}, } @article {pmid29027348, year = {2018}, author = {Bernal, P and Llamas, MA and Filloux, A}, title = {Type VI secretion systems in plant-associated bacteria.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {1-15}, pmid = {29027348}, issn = {1462-2920}, support = {BB/N002539/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, abstract = {The type VI secretion system (T6SS) is a bacterial nanomachine used to inject effectors into prokaryotic or eukaryotic cells and is thus involved in both host manipulation and interbacterial competition. The T6SS is widespread among Gram-negative bacteria, mostly within the Proteobacterium Phylum. This secretion system is commonly found in commensal and pathogenic plant-associated bacteria. Phylogenetic analysis of phytobacterial T6SS clusters shows that they are distributed in the five main clades previously described (group 1-5). The even distribution of the system among commensal and pathogenic phytobacteria suggests that the T6SS provides fitness and colonization advantages in planta and that the role of the T6SS is not restricted to virulence. This manuscript reviews the phylogeny and biological roles of the T6SS in plant-associated bacteria, highlighting a remarkable diversity both in terms of mechanism and function.}, } @article {pmid29027347, year = {2018}, author = {Rosenberg, J and Yeak, KC and Commichau, FM}, title = {A two-step evolutionary process establishes a non-native vitamin B6 pathway in Bacillus subtilis.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {156-168}, doi = {10.1111/1462-2920.13950}, pmid = {29027347}, issn = {1462-2920}, abstract = {Pyridoxal 5'-phosphate (PLP), the most important form of vitamin B6 serves as a cofactor for many proteins. Two alternative pathways for de novo PLP biosynthesis are known: the short deoxy-xylulose-5-phosphate (DXP)-independent pathway, which is present in the Gram-positive model bacterium Bacillus subtilis and the longer DXP-dependent pathway, which has been intensively studied in the Gram-negative model bacterium Escherichia coli. Previous studies revealed that bacteria contain many promiscuous enzymes causing a so-called 'underground metabolism', which can be important for the evolution of novel pathways. Here, we evaluated the potential of B. subtilis to use a truncated non-native DXP-dependent PLP pathway from E. coli for PLP synthesis. Adaptive laboratory evolution experiments revealed that two non-native enzymes catalysing the last steps of the DXP-dependent PLP pathway and two genomic alterations are sufficient to allow growth of vitamin B6 auxotrophic bacteria as rapid as the wild type. Thus, the existence of an underground metabolism in B. subtilis facilitates the generation of a pathway for synthesis of PLP using parts of a non-native vitamin B6 pathway. The introduction of non-native enzymes into a metabolic network and rewiring of native metabolism could be helpful to generate pathways that might be optimized for producing valuable substances.}, } @article {pmid29027346, year = {2018}, author = {Angel, R and Panhölzl, C and Gabriel, R and Herbold, C and Wanek, W and Richter, A and Eichorst, SA and Woebken, D}, title = {Application of stable-isotope labelling techniques for the detection of active diazotrophs.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {44-61}, pmid = {29027346}, issn = {1462-2920}, abstract = {Investigating active participants in the fixation of dinitrogen gas is vital as N is often a limiting factor for primary production. Biological nitrogen fixation is performed by a diverse guild of bacteria and archaea (diazotrophs), which can be free-living or symbionts. Free-living diazotrophs are widely distributed in the environment, yet our knowledge about their identity and ecophysiology is still limited. A major challenge in investigating this guild is inferring activity from genetic data as this process is highly regulated. To address this challenge, we evaluated and improved several 15 N-based methods for detecting N2 fixation activity (with a focus on soil samples) and studying active diazotrophs. We compared the acetylene reduction assay and the 15 N2 tracer method and demonstrated that the latter is more sensitive in samples with low activity. Additionally, tracing 15 N into microbial RNA provides much higher sensitivity compared to bulk soil analysis. Active soil diazotrophs were identified with a 15 N-RNA-SIP approach optimized for environmental samples and benchmarked to 15 N-DNA-SIP. Lastly, we investigated the feasibility of using SIP-Raman microspectroscopy for detecting 15 N-labelled cells. Taken together, these tools allow identifying and investigating active free-living diazotrophs in a highly sensitive manner in diverse environments, from bulk to the single-cell level.}, } @article {pmid29027341, year = {2018}, author = {Lopes, LD and Davis, EW and Pereira E Silva, MC and Weisberg, AJ and Bresciani, L and Chang, JH and Loper, JE and Andreote, FD}, title = {Tropical soils are a reservoir for fluorescent Pseudomonas spp. biodiversity.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {62-74}, doi = {10.1111/1462-2920.13957}, pmid = {29027341}, issn = {1462-2920}, abstract = {Fluorescent Pseudomonas spp. are widely studied for their beneficial activities to plants. To explore the genetic diversity of Pseudomonas spp. in tropical regions, we collected 76 isolates from a Brazilian soil. Genomes were sequenced and compared to known strains, mostly collected from temperate regions. Phylogenetic analyses classified the isolates in the P. fluorescens (57) and P. putida (19) groups. Among the isolates in the P. fluorescens group, most (37) were classified in the P. koreensis subgroup and two in the P. jessenii subgroup. The remaining 18 isolates fell into two phylogenetic subclades distinct from currently recognized P. fluorescens subgroups, and probably represent new subgroups. Consistent with their phylogenetic distance from described subgroups, the genome sequences of strains in these subclades are asyntenous to the genome sequences of members of their neighbour subgroups. The tropical isolates have several functional genes also present in known fluorescent Pseudomonas spp. strains. However, members of the new subclades share exclusive genes not detected in other subgroups, pointing to the potential for novel functions. Additionally, we identified 12 potential new species among the 76 isolates from the tropical soil. The unexplored diversity found in the tropical soil is possibly related to biogeographical patterns.}, } @article {pmid29024914, year = {2018}, author = {Jones, SE and Elliot, MA}, title = {'Exploring' the regulation of Streptomyces growth and development.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {25-30}, doi = {10.1016/j.mib.2017.09.009}, pmid = {29024914}, issn = {1879-0364}, mesh = {Bacterial Proteins/genetics/metabolism ; *Gene Expression Regulation, Bacterial ; Hyphae/genetics/growth & development/metabolism ; Spores, Bacterial/growth & development ; Streptomyces/*genetics/*growth & development/physiology ; Stress, Physiological/genetics ; }, abstract = {The Streptomyces life cycle encompasses three well-established developmental stages: vegetative hyphae, aerial hyphae and spores. Many regulators governing the transitions between these life cycle stages have been identified, and recent work is shedding light on their specific functions. A new discovery has shown Streptomyces can deviate from this classic life cycle through a process termed 'exploration', where cells rapidly traverse solid surfaces. Exploration does not require any of the traditional developmental regulators, and therefore provides an exciting new context in which to uncover novel developmental pathways. Here, we summarize our understanding of how Streptomyces exploration is controlled, and we speculate on how insight into classical regulation and stress response systems can inform future research into the regulation of exploratory growth.}, } @article {pmid29024751, year = {2018}, author = {Mokodongan, DF and Montenegro, J and Mochida, K and Fujimoto, S and Ishikawa, A and Kakioka, R and Yong, L and Mulis, and Hadiaty, RK and Mandagi, IF and Masengi, KWA and Wachi, N and Hashiguchi, Y and Kitano, J and Yamahira, K}, title = {Phylogenomics reveals habitat-associated body shape divergence in Oryzias woworae species group (Teleostei: Adrianichthyidae).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {194-203}, doi = {10.1016/j.ympev.2017.10.005}, pmid = {29024751}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Cell Nucleus/genetics ; DNA, Mitochondrial/genetics ; *Ecosystem ; Female ; *Genomics ; Geography ; Indonesia ; Male ; Mitochondria/genetics ; Oryzias/*anatomy & histology/*genetics ; *Phylogeny ; Principal Component Analysis ; Species Specificity ; }, abstract = {The Oryzias woworae species group, composed of O. asinua, O. wolasi, and O. woworae, is widely distributed in southeastern Sulawesi, an island in the Indo-Australian Archipelago. Deep-elongated body shape divergence is evident among these three species to the extent that it is used as a species-diagnostic character. These fishes inhabit a variety of habitats, ranging from upper streams to ponds, suggesting that the body shape divergence among the three species may reflect adaptation to local environments. First, our geometric morphometrics among eight local populations of this species group revealed that the three species cannot be separated by body shape and that riverine populations had more elongated bodies and longer caudal parts than lacustrine populations. Second, their phylogenetic relationships did not support the presence of three species; phylogenies using mitochondrial DNA and genomic data obtained from RNA-Seq revealed that the eight populations could not be sorted into three different clades representing three described species. Third, phylogenetic corrections of body shape variations and ancestral state reconstruction of body shapes demonstrated that body shape divergence between riverine and lacustrine populations persisted even if the phylogenies were considered and that body shape evolved rapidly irrespective of phylogeny. Sexual dimorphism in body shape was also evident, but the degree of dimorphism did not significantly differ between riverine and lacustrine populations after phylogenetic corrections, suggesting that sexual selection may not substantially contribute to geographical variations in body shape. Overall, these results indicate that the deep-elongated body shape divergence of the O. woworae species group evolved locally in response to habitat environments, such as water currents, and that a thorough taxonomic reexamination of the O. woworae species group may be necessary.}, } @article {pmid29024366, year = {2018}, author = {Hou, Z and Li, S}, title = {Tethyan changes shaped aquatic diversification.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {874-896}, doi = {10.1111/brv.12376}, pmid = {29024366}, issn = {1469-185X}, abstract = {The Tethys Ocean existed between the continents of Gondwana and Laurasia from the Triassic to the Pliocene. Analyses of multiple biogeographic and phylogenetic histories reveal that the subsequent breakup of the Tethys greatly influenced the distributions of many species. The ancestral Tethyan realm broke into five biogeographic provinces, including the present-day East Pacific, West Atlantic, East Atlantic, Mediterranean Sea, and Indo-West Pacific. Palaeogeographic maps illustrate the Mesozoic Atlantic opening, the Cenozoic closure of the Tethys, the Messinian Salinity Crisis, the mid-Miocene closure of the Central American Seaway, and Quaternary geological changes. Further, we consider Cenozoic sea-level changes and the formation of freshwater habitats. These reconstructions allow assessment of patterns of aquatic diversification for marine and freshwater animals, and comparison of vicariance and dispersal processes. Estimated divergence times indicate that fragmentation of the Tethys was responsible for the vicariant speciation of aquatic animals because these dates are consistent with associated tectonic events. The opening of the Atlantic Ocean during the Cretaceous is responsible for the earliest isolation between the West and East Atlantic. The mid-Miocene closure of the Tethys, which blocked global equatorial currents, appears to have isolated the Atlantic/Mediterranean Sea and Indo-West Pacific. Finally, formation of the Isthmus of Panama isolated East Pacific and West Atlantic marine organisms. Dispersals related to the Messinian Salinity Crisis and Quaternary sea-level changes influenced population structuring. Tethyan changes affected marine habitats, created new freshwater habitats, inland caves and ancient lakes along the Alps and Himalayas, and influenced anchialine caves at the edge of the ancient sea. The extensive new habitats provided opportunities for colonisation and rapid diversification. Future work should focus on testing the biological impact of the series of Tethyan changes.}, } @article {pmid29024277, year = {2018}, author = {Zwolak, R}, title = {How intraspecific variation in seed-dispersing animals matters for plants.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {897-913}, doi = {10.1111/brv.12377}, pmid = {29024277}, issn = {1469-185X}, abstract = {Seed dispersal by animals is a complex phenomenon, characterized by multiple mechanisms and variable outcomes. Most researchers approach this complexity by analysing context-dependency in seed dispersal and investigating extrinsic factors that might influence interactions between plants and seed dispersers. Intrinsic traits of seed dispersers provide an alternative way of making sense of the enormous variation in seed fates. I review causes of intraspecific variability in frugivorous and granivorous animals, discuss their effects on seed dispersal, and outline likely consequences for plant populations and communities. Sources of individual variation in seed-dispersing animals include sexual dimorphism, changes associated with growth and ageing, individual specialization, and animal personalities. Sexual dimorphism of seed-dispersing animals influences seed fate through diverse mechanisms that range from effects caused by sex-specific differences in body size, to influences of male versus female cognitive functions. These differences affect the type of seed treatment (e.g. dispersal versus predation), the number of dispersed seeds, distance of seed dispersal, and likelihood that seeds are left in favourable sites for seeds or seedlings. The best-documented consequences of individual differences associated with growth and ageing involve quantity of dispersed seeds and the quality of seed treatment in the mouth and gut. Individual specialization on different resources affects the number of dispersed plant species, and therefore the connectivity and architecture of seed-dispersal networks. Animal personalities might play an important role in shaping interactions between plants and dispersers of their seeds, yet their potential in this regard remains overlooked. In general, intraspecific variation in seed-dispersing animals often influences plants through effects of these individual differences on the movement ecology of the dispersers. Two conditions are necessary for individual variation to exert a strong influence on seed dispersal. First, the individual differences in traits should translate into differences in crucial characteristics of seed dispersal. Second, individual variation is more likely to be important when the proportions of particular types of individuals fluctuate strongly in a population or vary across space; when proportions are static, it is less likely that intraspecific differences will be responsible for changes in the dynamics and outcomes of plant-animal interactions. In conclusion, focusing on variation among foraging animals rather than on species averages might bring new, mechanistic insights to the phenomenon of seed dispersal. While this shift in perspective is unlikely to replace the traditional approach (based on the assumption that all important variation occurs among species), it provides a complementary alternative to decipher the enormous variation observed in animal-mediated seed dispersal.}, } @article {pmid29022067, year = {2018}, author = {Kutschera, A and Lamb, JJ}, title = {Cost-Effective Live Cell Density Determination of Liquid Cultured Microorganisms.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {231-236}, pmid = {29022067}, issn = {1432-0991}, mesh = {Bacterial Load/*instrumentation/*methods ; Colony Count, Microbial/*instrumentation/*methods ; Escherichia coli/*growth & development/isolation & purification ; Pseudomonas syringae/*growth & development/isolation & purification ; Saccharomyces cerevisiae/*growth & development/isolation & purification ; }, abstract = {Live monitoring of microorganisms growth in liquid medium is a desired parameter for many research fields. A wildly used approach for determining microbial liquid growth quantification is based on light scattering as the result of the physical interaction of light with microbial cells. These measurements are generally achieved using costly table-top instruments; however, a live, reliable, and straight forward instrument constructed using parts that are inexpensive may provide opportunities for many researchers. Here, such an instrument has been constructed and tested. It consists of modular test tube holding chambers, each with a low power monochromatic light-emitting diode, and a monolithic photodiode. A microcontroller connects to all modular chambers to control the diodes, and send the live data to either an LCD screen, or a computer. This work demonstrate that this modular instrument can determine precise cell concentrations for the bacteria Escherichia coli and Pseudomonas syringae pv. tomato DC3000, as well as Saccharomyces cerevisiae yeast.}, } @article {pmid29022066, year = {2018}, author = {Ten, LN and Elderiny, N and Lee, JJ and Lee, SY and Park, S and Lee, DS and Kim, MK and Jung, HY}, title = {Spirosoma harenae sp. nov., a Bacterium Isolated from a Sandy Beach.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {179-185}, pmid = {29022066}, issn = {1432-0991}, support = {NRF-2014H1C1A1066929//the Human Resource Training Program for Regional Innovation and Creativity through the Ministry of Education and National Research Foundation (NRF) of Korea/ ; grant 162S-4-3-1727//the Brain Pool Program of 2016 through the Korean Federation of Science and Technology Societies (KOFST) funded by the Ministry of Science, ICT and Future Planning, Republic of Korea/ ; }, mesh = {Aerobiosis ; Base Composition ; Cluster Analysis ; Cytophagaceae/*classification/genetics/*isolation & purification/physiology ; Cytosol/chemistry ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Fatty Acids/analysis ; Hydrogen-Ion Concentration ; Korea ; Phospholipids/analysis ; Phylogeny ; Quinones/analysis ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; Sodium Chloride/metabolism ; *Soil Microbiology ; Temperature ; Vitamin K 2/analysis ; }, abstract = {A Gram-stain-negative, non-motile, non-spore-forming, rod-shaped, aerobic bacterium, designated 15J8-9T, was isolated from a sandy beach in Jeju Island, South Korea. The isolate was able to grow between 10 and 30 °C, pH 5-8, and in presence of 0-1% (w/v) NaCl. Based on 16S rRNA gene phylogenetic analysis, the novel strain was closely related to members of the genus Spirosoma (96.1-90.9% similarities) and showed highest sequence similarity to Spirosoma panaciterrae DSM 21099T (96.1%). The G + C content of the genomic DNA of strain 15J8-9T was 45.1 mol%. The isolate contained menaquinone MK-7 as the predominant respiratory quinone, phosphatidylethanolamine as the major polar lipid, and summed feature 3 (C16:1 ω6c/C16:1 ω7c; 28.0%), C16:1 ω5c (23.4%), iso-C15:0 (13.5%), and C16:0 (11.5%) as the major fatty acids that supported the affiliation of strain 15J8-9T to the genus Spirosoma. The isolate could be differentiated clearly from recognized Spirosoma species on the basis of several phenotypic, genotypic and chemotaxonomic features. Therefore, strain 15J8-9T is considered to represent a novel species of the genus the genus Spirosoma, for which the name Spirosoma harenae sp. nov. is proposed. The type strain is 15J8-9T (= KCTC 52030T = JCM 31993T).}, } @article {pmid29017853, year = {2018}, author = {Danderson, CA and Downie, SR and Hermann, M}, title = {Rampant polyphyly in the Arracacia clade (Apiaceae) and an assessment of the phylogenetic utility of 20 noncoding plastid loci.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {286-305}, doi = {10.1016/j.ympev.2017.10.006}, pmid = {29017853}, issn = {1095-9513}, mesh = {Apiaceae/*classification/genetics ; Base Sequence ; Bayes Theorem ; Cell Nucleus/genetics ; DNA, Chloroplast/chemistry/isolation & purification/metabolism ; Genetic Loci ; Introns ; Phylogeny ; Plastids/genetics ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {The Arracacia clade (Apiaceae, Apioideae) is a heterogeneous assemblage of 12 genera, comprising 111 known species distributed in high montane temperate and sub-alpine habitats of meso- and South America. Previous studies have indicated that the genera Arracacia, Coulterophytum, and Prionosciadium are polyphyletic, but for the most part relationships among the members of the clade are largely unknown. Initially, cladistic analyses of nrDNA ITS sequences were carried out on 212 accessions (122 taxa), representing 92 species of the Arracacia clade and outgroups from the closely-related páramo genera Cotopaxia, Niphogeton, and Perissocoeleum and members of the Perennial Endemic North American clade and its allies. Using the ITS results to inform sampling of a small subset of taxa, a pilot study examining the phylogenetic utility of 20 noncoding chloroplast loci was subsequently performed to identify those regions most useful at resolving relationships. A cost-benefit analysis determined that five loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, psbD-trnT, ndhA intron) would maximize resolution and branch support in the clade. Cladistic analyses of four of these loci (trnQ-5'rps16, trnD-trnT, rpl32-trnL, ndhA intron) and the ITS region, separately and combined, revealed that Arracacia, Coaxana, Coulterophytum, Prionosciadium, and Rhodosciadium are each polyphyletic and that Donnellsmithia and Myrrhidendron are each monophyletic. Although most relationships in the Arracacia clade and among the closely-related genera Cotopaxia, Niphogeton, and Perissocoeleum are poorly resolved and supported, ten groups are recognized for future revisionary studies. Polyploidy and rapid species radiation have likely confounded generic circumscriptions and interpretation of relationships.}, } @article {pmid28994444, year = {2018}, author = {Andreoni, M and Mussi, C and Bellagamba, R and Di Campli, F and Montinaro, V and Babiloni, C}, title = {Biomarkers of monitoring and functional reserve of physiological systems over time in HIV: expert opinions for effective secondary prevention.}, journal = {The new microbiologica}, volume = {41}, number = {1}, pages = {1-25}, pmid = {28994444}, issn = {1121-7138}, mesh = {Aging ; Anti-Retroviral Agents/adverse effects/therapeutic use ; Biomarkers ; Bone Density/drug effects ; Cognition Disorders/etiology/pathology ; HIV Infections/*complications/drug therapy ; Humans ; Kidney/pathology/physiology ; Kidney Diseases/etiology ; Risk Factors ; Secondary Prevention ; }, abstract = {HIV-positive individuals are more vulnerable to poor health than HIV-negative individuals. This vulnerability is characterized by a higher risk of several common, age-related health problems, even after adjustment for established risk factors. This expert opinion report aims at identifying the optimal biomarkers for monitoring the structural integrity and function of physiological systems at risk across aging in HIV-seropositive subjects. These biomarkers, readily available locally and relatively cost-effective for clinicians in primary and secondary care, should allow early detection of the first preclinical structural and functional changes in renal, brain, cardiovascular, and skeleton systems or apparatus in HIV subjects across aging. A particular interest of this report is the definition of the concept of biomarker of the "organ functional reserve". This definition emphasizes the fact that some biomarkers for monitoring the molecular, structural and functional integrity of a given organ reflect a level of impairment that is basically irremediable despite effective pharmacological or nonpharmacological intervention.}, } @article {pmid28990321, year = {2018}, author = {Galetti, M and Moleón, M and Jordano, P and Pires, MM and Guimarães, PR and Pape, T and Nichols, E and Hansen, D and Olesen, JM and Munk, M and de Mattos, JS and Schweiger, AH and Owen-Smith, N and Johnson, CN and Marquis, RJ and Svenning, JC}, title = {Ecological and evolutionary legacy of megafauna extinctions.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {845-862}, doi = {10.1111/brv.12374}, pmid = {28990321}, issn = {1469-185X}, abstract = {For hundreds of millions of years, large vertebrates (megafauna) have inhabited most of the ecosystems on our planet. During the late Quaternary, notably during the Late Pleistocene and the early Holocene, Earth experienced a rapid extinction of large, terrestrial vertebrates. While much attention has been paid to understanding the causes of this massive megafauna extinction, less attention has been given to understanding the impacts of loss of megafauna on other organisms with whom they interacted. In this review, we discuss how the loss of megafauna disrupted and reshaped ecological interactions, and explore the ecological consequences of the ongoing decline of large vertebrates. Numerous late Quaternary extinct species of predators, parasites, commensals and mutualistic partners were associated with megafauna and were probably lost due to their strict dependence upon them (co-extinctions). Moreover, many extant species have megafauna-adapted traits that provided evolutionary benefits under past megafauna-rich conditions, but are now of no or limited use (anachronisms). Morphological evolution and behavioural changes allowed some of these species partially to overcome the absence of megafauna. Although the extinction of megafauna led to a number of co-extinction events, several species that likely co-evolved with megafauna established new interactions with humans and their domestic animals. Species that were highly specialized in interactions with megafauna, such as large predators, specialized parasites, and large commensalists (e.g. scavengers, dung beetles), and could not adapt to new hosts or prey were more likely to die out. Partners that were less megafauna dependent persisted because of behavioural plasticity or by shifting their dependency to humans via domestication, facilitation or pathogen spill-over, or through interactions with domestic megafauna. We argue that the ongoing extinction of the extant megafauna in the Anthropocene will catalyse another wave of co-extinctions due to the enormous diversity of key ecological interactions and functional roles provided by the megafauna.}, } @article {pmid28989098, year = {2018}, author = {Garbino, GST and Martins-Junior, AMG}, title = {Phenotypic evolution in marmoset and tamarin monkeys (Cebidae, Callitrichinae) and a revised genus-level classification.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {156-171}, doi = {10.1016/j.ympev.2017.10.002}, pmid = {28989098}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; *Biological Evolution ; Body Size ; Callithrix/anatomy & histology/classification ; Callitrichinae/anatomy & histology/*classification ; Geography ; Homing Behavior ; Likelihood Functions ; Phenotype ; Phylogeny ; Skull/anatomy & histology ; Vocalization, Animal/physiology ; }, abstract = {Marmosets and tamarins (Cebidae, Callitrichinae) constitute the most species-rich subfamily of New World monkeys and one of the most diverse phenotypically. Despite the profusion of molecular phylogenies of the group, the evolution of phenotypic characters under the rapidly-emerging consensual phylogeny of the subfamily has been little studied, resulting in taxonomic proposals that have limited support from other datasets. We examined the evolution of 18 phenotypic traits (5 continuous and 13 discrete), including pelage, skull, dentition, postcrania, life-history and vocalization variables in a robust molecular phylogeny of marmoset and tamarin monkeys, quantifying their phylogenetic signal and correlations among some of the traits. At the family level, our resulting topology supports owl monkeys (Aotinae) as sister group of Callitrichinae. The topology of the callitrichine tree was congruent with previous studies except for the position of the midas group of Saguinus tamarins, which placement as sister of the bicolor group did not receive significant statistical support in both Maximum Parsimony and Bayesian Inference analyses. Our results showed that the highest value of phylogenetic signal among continuous traits was displayed by the long call character and the lowest was exhibited in the home range, intermediate values were found in characters related to osteology and skull size. Among discrete traits, pelage and osteology had similar phylogenetic signal. Based on genetic, osteological, pelage and vocalization data, we present an updated genus-level taxonomy of Callitrichinae, which recognizes six genera in the subfamily: Callimico, Callithrix, Cebuella, Mico, Leontopithecus and Saguinus. To reflect their phenotypic distinctiveness and to avoid the use of the informal "species group", we subdivided Saguinus in the subgenera Leontocebus, Saguinus and Tamarinus (revalidated here).}, } @article {pmid28989097, year = {2018}, author = {Lindgren, AR and Anderson, FE}, title = {Assessing the utility of transcriptome data for inferring phylogenetic relationships among coleoid cephalopods.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {330-342}, doi = {10.1016/j.ympev.2017.10.004}, pmid = {28989097}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Cephalopoda/*classification/genetics ; Decapodiformes/classification/genetics ; Fossils ; Likelihood Functions ; Phylogeny ; *Transcriptome ; }, abstract = {Historically, deep-level relationships within the molluscan class Cephalopoda (squids, cuttlefishes, octopods and their relatives) have remained elusive due in part to the considerable morphological diversity of extant taxa, a limited fossil record for species that lack a calcareous shell and difficulties in sampling open ocean taxa. Many conflicts identified by morphologists in the early 1900s remain unresolved today in spite of advances in morphological, molecular and analytical methods. In this study we assess the utility of transcriptome data for resolving cephalopod phylogeny, with special focus on the orders of Decapodiformes (open-eye squids, bobtail squids, cuttlefishes and relatives). To do so, we took new and previously published transcriptome data and used a unique cephalopod core ortholog set to generate a dataset that was subjected to an array of filtering and analytical methods to assess the impacts of: taxon sampling, ortholog number, compositional and rate heterogeneity and incongruence across loci. Analyses indicated that datasets that maximized taxonomic coverage but included fewer orthologs were less stable than datasets that sacrificed taxon sampling to increase the number of orthologs. Clades recovered irrespective of dataset, filtering or analytical method included Octopodiformes (Vampyroteuthis infernalis + octopods), Decapodiformes (squids, cuttlefishes and their relatives), and orders Oegopsida (open-eyed squids) and Myopsida (e.g., loliginid squids). Ordinal-level relationships within Decapodiformes were the most susceptible to dataset perturbation, further emphasizing the challenges associated with uncovering relationships at deep nodes in the cephalopod tree of life.}, } @article {pmid28988682, year = {2018}, author = {Traversa, D and Joachim, A}, title = {The 3Rs Concept: Time to Change How We Evaluate the Efficacy of Anthelmintics in Companion Animals.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {41-52}, doi = {10.1016/j.pt.2017.09.002}, pmid = {28988682}, issn = {1471-5007}, mesh = {Animals ; Anthelmintics/*administration & dosage/standards ; Cat Diseases/drug therapy/*prevention & control ; Cats ; Dog Diseases/drug therapy/*prevention & control ; Dogs ; Drug Evaluation/standards/*veterinary ; Helminthiasis, Animal/drug therapy/*prevention & control ; Pets/*parasitology ; }, abstract = {Experimental infections are required by current guidelines for investigating the efficacy of anthelmintics in dogs and cats. Recently, alternatives to experimental infections and the sacrificing of research dogs and cats have been evaluated, and novel conceptual investigations and methods of examination have been explored. Several of these approaches could potentially be used in efficacy studies for anthelmintics in dogs and cats. Here, we provide food for thought towards using new tools for evaluating the efficacy of anthelmintics in companion animals, for promoting the value of field trials, and for updating the existing guidelines for the efficacy testing of anthelmintics in dogs and cats.}, } @article {pmid28988156, year = {2018}, author = {Radlinski, L and Conlon, BP}, title = {Antibiotic efficacy in the complex infection environment.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {19-24}, pmid = {28988156}, issn = {1879-0364}, support = {K22 AI125501/AI/NIAID NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/adverse effects/*therapeutic use ; Bacterial Infections/*drug therapy/microbiology ; Drug Resistance, Microbial ; Host-Pathogen Interactions/*drug effects/physiology ; Humans ; Microbial Interactions/*drug effects ; Microbial Sensitivity Tests/statistics & numerical data ; Treatment Outcome ; }, abstract = {Accurate prediction of antimicrobial efficacy is essential for successful treatment of bacterial infection. Beyond genetically encoded mechanisms of antibiotic resistance, the determinants of antibiotic susceptibility during infection remain poorly understood, and treatment failure is common. Traditional antibiotic susceptibility testing fails to account for extrinsic determinants of antibiotic susceptibility present in the complex infection environment and is therefore a poor predictor of antibiotic treatment outcome. Here we discuss how host-pathogen interaction, microbial interspecies interaction, and metabolic heterogeneity contribute to the success or failure of antibiotic therapy. Consideration of these factors during the treatment of disease will improve our ability to successfully resolve recalcitrant bacterial infection and improve patient health.}, } @article {pmid28987637, year = {2018}, author = {Lv, YY and He, K and Klaus, S and Brown, RM and Li, JT}, title = {A comprehensive phylogeny of the genus Kurixalus (Rhacophoridae, Anura) sheds light on the geographical range evolution of frilled swamp treefrogs.}, journal = {Molecular phylogenetics and evolution}, volume = {121}, number = {}, pages = {224-232}, doi = {10.1016/j.ympev.2017.09.019}, pmid = {28987637}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification ; Asia ; Base Sequence ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Fossils ; *Geography ; *Phylogeny ; Time Factors ; *Wetlands ; }, abstract = {Currently, the genus Kurixalus comprises 14 species distributed in Southern, Southeast and East Asia. Because of their relatively low dispersal capability and intolerance of seawater, this group is ideal for the study of terrestrial range evolution, especially that portion of its range that extends into the island archipelagos of Southern Asia. We assembled a large dataset of mitochondrial and nuclear genes, and estimated phylogeny by maximum likelihood and Bayesian methods, and we explored the history of each species via divergence-time estimation based on fossil-calibrations. A variety of ancestral-area reconstruction strategies were employed to estimate past changes of the species' geographical range, and to evaluate the impact of different abiotic barriers on range evolution. We found that frilled swamp treefrogs probably originated in Taiwan or South Vietnam in the Oligocene. Alternatively, the lineage leading to Kurixalus appendiculatus strongly supports a hypothesis of terrestrial connection between the Indian and Asian continents in the Oligocene. The outcome of both our divergence-time estimates and ancestral-area reconstruction suggests that the divergence between species from Indochina and Taiwan can probably be attributed to the opening of the South China Sea, approximately 33 million years ago. We could not find evidence for dispersal between mainland China and Taiwan Island. Formation of both Mekong and Red River valleys did not have any impact on Kurixalus species diversification. However, coincidence in timing of climate change and availability of plausible dispersal routes from the Oligocene to the middle Miocene, plausibly implied that Kurixalus diversification in Asia resulted from contemporaneous, climate-induced environmental upheaval (Late Oligocene Warming at 29 Ma; Mi-1 glaciation since 24.4-21.5 Ma; Mid-Miocene Climatic Optimum at 14 Ma), which alternatively opened and closed dispersal routes.}, } @article {pmid28987636, year = {2018}, author = {Valderrama, E and Richardson, JE and Kidner, CA and Madriñán, S and Stone, GN}, title = {Transcriptome mining for phylogenetic markers in a recently radiated genus of tropical plants (Renealmia L.f., Zingiberaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {119}, number = {}, pages = {13-24}, doi = {10.1016/j.ympev.2017.10.001}, pmid = {28987636}, issn = {1095-9513}, mesh = {Bayes Theorem ; DNA, Ribosomal/genetics ; Genetic Markers ; Introns/genetics ; *Phylogeny ; RNA, Messenger/genetics/metabolism ; Sequence Analysis, DNA ; Species Specificity ; Transcriptome/*genetics ; *Tropical Climate ; Zingiberaceae/*classification/*genetics ; }, abstract = {The reconstruction of relationships within species-rich groups that have recently evolved in biodiversity hotspots is hampered by a lack of phylogenetically informative markers. It is also made difficult by the lack of sampling necessary to reconstruct a species-level phylogeny. We use transcriptome mining to search for markers to reconstruct a phylogeny of the amphi-Atlantic genus Renealmia L. f. (Zingiberaceae). We recover seven introns from single copy genes and use them to reconstruct the phylogeny of the genus together with a commonly used phylogenetic marker, internal transcribed spacers of ribosomal DNA (ITS) that has previously been used to reconstruct the phylogeny of the genus. We targeted genes with low numbers of base pairs that improves sequencing success using highly degraded DNA from herbarium specimens. The use of herbarium specimens greatly increased the number of species in the study as these were readily available in historical collections. Data were obtained for 14 of the 17 African species and 54 of the 65 Neotropical species. The phylogeny was well-supported for a number of Renealmia subgroups although relationships among those clades remained poorly supported.}, } @article {pmid28986951, year = {2018}, author = {Duthie, AB and Bocedi, G and Germain, RR and Reid, JM}, title = {Evolution of precopulatory and post-copulatory strategies of inbreeding avoidance and associated polyandry.}, journal = {Journal of evolutionary biology}, volume = {31}, number = {1}, pages = {31-45}, pmid = {28986951}, issn = {1420-9101}, mesh = {Animals ; *Biological Evolution ; Copulation/physiology ; Female ; *Inbreeding ; Male ; *Models, Biological ; Sexual Behavior, Animal/*physiology ; }, abstract = {Inbreeding depression is widely hypothesized to drive adaptive evolution of precopulatory and post-copulatory mechanisms of inbreeding avoidance, which in turn are hypothesized to affect evolution of polyandry (i.e. female multiple mating). However, surprisingly little theory or modelling critically examines selection for precopulatory or post-copulatory inbreeding avoidance, or both strategies, given evolutionary constraints and direct costs, or examines how evolution of inbreeding avoidance strategies might feed back to affect evolution of polyandry. Selection for post-copulatory inbreeding avoidance, but not for precopulatory inbreeding avoidance, requires polyandry, whereas interactions between precopulatory and post-copulatory inbreeding avoidance might cause functional redundancy (i.e. 'degeneracy') potentially generating complex evolutionary dynamics among inbreeding strategies and polyandry. We used individual-based modelling to quantify evolution of interacting precopulatory and post-copulatory inbreeding avoidance and associated polyandry given strong inbreeding depression and different evolutionary constraints and direct costs. We found that evolution of post-copulatory inbreeding avoidance increased selection for initially rare polyandry and that evolution of a costly inbreeding avoidance strategy became negligible over time given a lower-cost alternative strategy. Further, fixed precopulatory inbreeding avoidance often completely precluded evolution of polyandry and hence post-copulatory inbreeding avoidance, but fixed post-copulatory inbreeding avoidance did not preclude evolution of precopulatory inbreeding avoidance. Evolution of inbreeding avoidance phenotypes and associated polyandry is therefore affected by evolutionary feedbacks and degeneracy. All else being equal, evolution of precopulatory inbreeding avoidance and resulting low polyandry is more likely when post-copulatory inbreeding avoidance is precluded or costly, and evolution of post-copulatory inbreeding avoidance greatly facilitates evolution of costly polyandry.}, } @article {pmid28986238, year = {2018}, author = {Villalta, I and Amor, F and Galarza, JA and Dupont, S and Ortega, P and Hefetz, A and Dahbi, A and Cerdá, X and Boulay, R}, title = {Origin and distribution of desert ants across the Gibraltar Straits.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {122-134}, doi = {10.1016/j.ympev.2017.09.026}, pmid = {28986238}, issn = {1095-9513}, mesh = {Africa, Northern ; Animals ; Ants/anatomy & histology/genetics/*physiology ; Bayes Theorem ; *Biological Evolution ; Demography ; Discriminant Analysis ; Europe ; Genetic Variation ; Gibraltar ; Hydrocarbons/metabolism ; Likelihood Functions ; Male ; Microsatellite Repeats/genetics ; Models, Biological ; Morocco ; Phylogeny ; Phylogeography ; Principal Component Analysis ; }, abstract = {The creation of geographic barriers has long been suspected to contribute to the formation of new species. We investigated the phylogeography of desert ants in the western Mediterranean basin in order to elucidate their mode of diversification. These insects which have a low dispersal capacity are recently becoming important model systems in evolutionary studies. We conducted an extensive sampling of species belonging to the Cataglyphis albicans group in the Iberian Peninsula (IP) and the northern Morocco (North Africa; NA). We then combined genetic, chemical and morphological analyses. The results suggest the existence of at least three and five clades in the IP and NA, respectively, whose delineation partially encompass current taxonomic classification. The three Iberian clades are monophyletic, but their origin in NA is uncertain (79% and 22% for Bayesian and Maximum Likelihood support, respectively). The estimation of divergence time suggests that a speciation process was initiated after the last reopening of the Gibraltar Straits ≈5.33 Ma. In the IP, the clades are parapatric and their formation may have been triggered by the fragmentation of a large population during the Pleistocene due to extended periods of glaciation. This scenario is supported by demographic analyses pointing at a recent expansion of Iberian populations that contrasts with the progressive contraction of the NA clades. Niche modeling reveals that this area, governed by favorable climatic conditions for desert ants, has recently increased in the IP and decreased in NA. Altogether, our data points at geoclimatic events as major determinants of species formation in desert ants, reinforcing the role of allopatric speciation.}, } @article {pmid28986237, year = {2018}, author = {Liu, Y and Song, F and Jiang, P and Wilson, JJ and Cai, W and Li, H}, title = {Compositional heterogeneity in true bug mitochondrial phylogenomics.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {135-144}, doi = {10.1016/j.ympev.2017.09.025}, pmid = {28986237}, issn = {1095-9513}, mesh = {Animals ; Base Composition ; Base Sequence ; Bayes Theorem ; Genetic Variation ; *Genome, Mitochondrial ; Heteroptera/*genetics ; Likelihood Functions ; Mitochondria/*genetics ; *Phylogeny ; }, abstract = {Mitochondrial phylogenomics is often controversial, in particular for inferring deep relationships. The recent rapid increase of mitochondrial genome data provides opportunities for better phylogenetic estimates and assessment of potential biases resulting from heterogeneity in nucleotide composition and mutation rates. Here, we gathered 76 mitochondrial genome sequences for Heteroptera representing all seven infraorders, including 17 newly sequenced mitochondrial genomes. We found strong heterogeneity in base composition and contrasting evolutionary rates among heteropteran mitochondrial genomes, which affected analyses with various datasets and partitioning schemes under site-homogeneous models and produced false groupings of unrelated taxa exhibiting similar base composition and accelerated evolutionary rates. Bayesian analyses using a site-heterogeneous mixture CAT+GTR model showed high congruence of topologies with the currently accepted phylogeny of Heteroptera. The results confirm the monophyly of the six infraorders within Heteroptera, except for Cimicomorpha which was recovered as two paraphyletic clades. The monophyly of Terheteroptera (Cimicomorpha and Pentatomomorpha) and Panheteroptera (Nepomorpha, Leptopodomorpha and Terheteroptera) was recovered demonstrating a significant improvement over previous studies using mitochondrial genome data. Our study shows the power of the site-heterogeneous mixture models for resolving phylogenetic relationships with Heteroptera and provides one more case showing that model adequacy is critical for accurate tree reconstruction in mitochondrial phylogenomics.}, } @article {pmid28986236, year = {2018}, author = {Matenaar, D and Fingerle, M and Heym, E and Wirtz, S and Hochkirch, A}, title = {Phylogeography of the endemic grasshopper genus Betiscoides (Lentulidae) in the South African Cape Floristic Region.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {318-329}, doi = {10.1016/j.ympev.2017.09.024}, pmid = {28986236}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Bayes Theorem ; Biological Evolution ; DNA/chemistry/isolation & purification/metabolism ; Genetic Variation ; Grasshoppers/*classification/genetics ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Sequence Alignment ; Sequence Analysis, DNA ; South Africa ; }, abstract = {Vicariance and dispersal are two important processes shaping biodiversity patterns. The South African Cape Floristic Region (CFR) is known for its high biotic diversity and endemism. However, studies on the phylogeography of endemic invertebrates in this biodiversity hotspot are still scarce. Here, we present a phylogenetic study of the flightless grasshopper genus Betiscoides, which is endemic to the CFR and strongly associated with restio plants (Restionaceae). We hypothesized that the genus originated in the southwestern part of the CFR, that differentiation within the genus is mainly an effect of vicariance and that the three known species only represent a minor fraction of the real genetic diversity of the genus. We inferred the phylogeny based on sequences of three mitochondrial and two nuclear genes from 99 Betiscoides specimens collected across the CFR. Furthermore, we conducted a SDIVA analysis to detect distributions of ancestral nodes and the possible spatial origin of these lineages. Strong differentiation among genetic lineages was shown. The ancestor of this genus was most likely distributed in the southwestern CFR. Five major lineages were detected, three of which were ancestrally distributed in the southwestern CFR. The ancestors of the two other lineages were distributed in the northern and eastern margins of the CFR. A total of 24 divergent evolutionary lineages were found, reflecting the geographical isolation of restio-dominated fynbos habitats. Dispersal played a more prominent role than expected in differentiation of Betiscoides. While the five main lineages were separated during a first phase via dispersal, differentiation occurred later and on smaller spatial scale, predominantly driven by isolation in montane refugia (i.e. vicariance). Our study also suggests that flightless insect taxa likely show high levels of differentiation in biodiversity hotspots with their taxonomy often being incomplete.}, } @article {pmid28986107, year = {2018}, author = {Thompson, RCA and Lymbery, AJ and Godfrey, SS}, title = {Parasites at Risk - Insights from an Endangered Marsupial.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {12-22}, doi = {10.1016/j.pt.2017.09.001}, pmid = {28986107}, issn = {1471-5007}, mesh = {Animals ; *Endangered Species ; *Extinction, Biological ; Host Specificity ; Host-Parasite Interactions ; Marsupialia/*parasitology ; }, abstract = {Parasites are the most abundant form of life on earth and are vital components of ecosystem health. Yet, it is only relatively recently that attention has been given to the risks of extinction that parasites face when their hosts, particularly wildlife, are endangered. In such circumstances, parasites that are host-specific with complicated life cycles are most at risk. Such extinction/coextinction events have been poorly documented, principally because of the difficulties of following such extinction processes in nature. Fortunately, we were presented with the rare opportunity to catalogue an endangered Australian marsupial's parasites; we present our near-complete catalogue here. We incorporate this catalogue into a predictive framework to understand which parasites might be most vulnerable to coextinction, which we hope will serve as a model for endangered hosts and their parasites elsewhere.}, } @article {pmid28984410, year = {2018}, author = {Tragin, M and Zingone, A and Vaulot, D}, title = {Comparison of coastal phytoplankton composition estimated from the V4 and V9 regions of the 18S rRNA gene with a focus on photosynthetic groups and especially Chlorophyta.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {506-520}, doi = {10.1111/1462-2920.13952}, pmid = {28984410}, issn = {1462-2920}, abstract = {We compared the composition of eukaryotic communities using two genetic markers (18S rRNA V4 and V9 regions) at 27 sites sampled during Ocean Sampling Day 2014, with a focus on photosynthetic groups and, more specifically green algae (Chlorophyta). Globally, the V4 and V9 regions of the 18S rRNA gene provided similar images of alpha diversity and ecological patterns. However, V9 provided 20% more OTUs built at 97% identity than V4. 34% of the genera were found with both markers and, of the remnant, 22% were found only with V4 and 44% only with V9. For photosynthetic groups, V4 and V9 performed equally well to describe global communities at different taxonomic levels from the division to the genus and provided similar Chlorophyta distribution patterns. However, at lower taxonomic level, the V9 dataset failed for example to describe the diversity of Dolichomastigales (Chlorophyta, Mamiellophyceae) emphasizing the lack of V9 sequences for this group and the importance of the reference database for metabarcode analysis. We conclude that in order to address questions regarding specific groups (e.g., a given genus), it is necessary to choose the marker based not only on the genetic divergence within this group but also on the existence of reference sequences in databases.}, } @article {pmid28977760, year = {2018}, author = {Burchard, H and Schuttelaars, HM and Ralston, DK}, title = {Sediment Trapping in Estuaries.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {371-395}, doi = {10.1146/annurev-marine-010816-060535}, pmid = {28977760}, issn = {1941-0611}, abstract = {Estuarine turbidity maxima (ETMs) are generated by a large suite of hydrodynamic and sediment dynamic processes, leading to longitudinal convergence of cross-sectionally integrated and tidally averaged transport of cohesive and noncohesive suspended particulate matter (SPM). The relative importance of these processes for SPM trapping varies substantially among estuaries depending on topography, fluvial and tidal forcing, and SPM composition. The high-frequency dynamics of ETMs are constrained by interactions with the low-frequency dynamics of the bottom pool of easily erodible sediments. Here, we use a transport decomposition to present processes that lead to convergent SPM transport, and review trapping mechanisms that lead to ETMs at the landward limit of the salt intrusion, in the freshwater zone, at topographic transitions, and by lateral processes within the cross section. We use model simulations of example estuaries to demonstrate the complex concurrence of ETM formation mechanisms. We also discuss how changes in SPM trapping mechanisms, often caused by direct human interference, can lead to the generation of hyperturbid estuaries.}, } @article {pmid28975611, year = {2018}, author = {Liao, WB and Huang, Y and Zeng, Y and Zhong, MJ and Luo, Y and Lüpold, S}, title = {Ejaculate evolution in external fertilizers: Influenced by sperm competition or sperm limitation?.}, journal = {Evolution; international journal of organic evolution}, volume = {72}, number = {1}, pages = {4-17}, doi = {10.1111/evo.13372}, pmid = {28975611}, issn = {1558-5646}, abstract = {The evolution of sperm quality and quantity is shaped by various selective processes, with sperm competition generally considered the primary selective agent. Particularly in external fertilizers, however, sperm limitation through gamete dispersal can also influence gamete investments, but empirical data examining this effect are limited. Here, we studied the relative importance of sperm competition and the spawning conditions in explaining the macroevolutionary patterns of sperm size and number within two taxa with external fertilization but differences in their reproductive biology. In frogs, sperm swim slowly but for up to hours as they penetrate the gelatinous egg coating, whereas fish sperm typically swim fast, are very short-lived (seconds to minutes), and often face a relatively higher risk of being moved away from the ova by currents. Our phylogenetic models and path analyses revealed different trajectories of ejaculate evolution in these two taxa. Sperm size and number responded primarily to variation in sperm competition in the anurans, but more strongly to egg number and water turbulence in the fishes. Whereas the results across anurans align with the general expectation that sexual selection is the main driver of ejaculate evolution, our findings across the fishes suggest that sperm limitation has been underappreciated.}, } @article {pmid28974446, year = {2018}, author = {Chaudhary, P and Kumar, R and Sagar, V and Sarkar, S and Singh, R and Ghosh, S and Singh, S and Chakraborti, A}, title = {Assessment of Cpa, Scl1 and Scl2 in clinical group A streptococcus isolates and patients from north India: an evaluation of the host pathogen interaction.}, journal = {Research in microbiology}, volume = {169}, number = {1}, pages = {11-19}, doi = {10.1016/j.resmic.2017.09.002}, pmid = {28974446}, issn = {1769-7123}, mesh = {Adolescent ; Bacterial Proteins/*genetics/metabolism ; Child ; Child, Preschool ; Collagen/*genetics/metabolism ; Female ; Host-Pathogen Interactions ; Humans ; India ; Male ; Streptococcal Infections/*microbiology ; Streptococcus pyogenes/classification/genetics/*isolation & purification/metabolism ; }, abstract = {Group A streptococcus (GAS) infection remains a major concern due to multiple diseases including pharyngitis, impetigo, acute rheumatic fever (ARF) and rheumatic heart disease (RHD). It uses different adhesins and virulence factors like Cpa (collagen binding protein) and Scl (collagen-like protein) in its pathogenicity. Scl having similarities with human collagen may contribute to inducing autoimmunity in the host. Here we assessed gene expression, antibody titer of Cpa, Scl1 and Scl2 in both clinical GAS isolates (n = 45) and blood (n = 45) obtained from pharyngitis, ARF (acute rheumatic fever) and RHD respectively. Skin isolates (n = 30) were obtained from impetigo patients. The study revealed a total of 27 GAS emm types. Frequency of cpa, scl1, scl2 was high in ARF isolates. The antibody titer of these proteins was high in all isolates, and also in patients with pharyngitis and ARF. All isolates showed high binding affinity toward collagen I and IV, which further indicates a potential host pathogen interaction. Our study reflects a strong association of Cpa and Scls in early and post-GAS pathogenicity. However, the increased antibody titer of Scl1 and Scl2 during ARF may be attributed to a cogent immune response in the host.}, } @article {pmid28974445, year = {2018}, author = {Silva, AF and Dos Santos, AR and Coelho Trevisan, DA and Ribeiro, AB and Zanetti Campanerut-Sá, PA and Kukolj, C and de Souza, EM and Cardoso, RF and Estivalet Svidzinski, TI and de Abreu Filho, BA and Junior, MM and Graton Mikcha, JM}, title = {Cinnamaldehyde induces changes in the protein profile of Salmonella Typhimurium biofilm.}, journal = {Research in microbiology}, volume = {169}, number = {1}, pages = {33-43}, doi = {10.1016/j.resmic.2017.09.007}, pmid = {28974445}, issn = {1769-7123}, mesh = {Acrolein/*analogs & derivatives/pharmacology ; Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/chemistry/genetics/*metabolism ; Biofilms/*drug effects ; Microbial Sensitivity Tests ; Proteomics ; Salmonella typhimurium/*drug effects/genetics/metabolism ; }, abstract = {The effect of cinnamaldehyde against biofilm cells of Salmonella Typhimurium ATCC 14028 was evaluated. We also assessed differential protein patterns that were expressed by biofilms compared with planktonic cells and protein expression by cinnamaldehyde-treated biofilms cells. This compound decreased biofilm biomass and metabolic activity of biofilms at both concentrations tested. Cinnamaldehyde treatment reduced the number of attached cells in polypropylene, reflected by colony count and scanning electron microscopy. The proteomic analysis of biofilms compared with planktonic cells indicated that several proteins were upregulated or downregulated, especially proteins that are involved in energy metabolism. Peroxiredoxin, ATP synthase alpha chain protein, conjugal transfer nickase/helicase TraI and elongation factor G were upregulated in untreated-biofilm cells, and their expression decreased as a function of cinnamaldehyde treatment. Cinnamaldehyde had antibiofilm activity, and several differentially expressed proteins identified provide potential and interesting targets to explore new control strategies for S. Typhimurium biofilms.}, } @article {pmid28968546, year = {2018}, author = {Gamba, P and Zenkin, N}, title = {Transcription fidelity and its roles in the cell.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {13-18}, pmid = {28968546}, issn = {1879-0364}, support = {//Wellcome Trust/United Kingdom ; BB/L010003/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; 102851//Wellcome Trust/United Kingdom ; }, mesh = {Catalytic Domain/genetics ; DNA-Directed RNA Polymerases/metabolism ; Models, Molecular ; RNA/*genetics ; *Transcription, Genetic ; }, abstract = {Accuracy of transcription is essential for productive gene expression, and the past decade has brought new understanding of the mechanisms ensuring transcription fidelity. The discovery of a new catalytic domain, the Trigger Loop, revealed that RNA polymerase can actively choose the correct substrates. Also, the intrinsic proofreading activity was found to proceed via a ribozyme-like mechanism, whereby the erroneous nucleoside triphosphate (NTP) helps its own excision. Factor-assisted proofreading was shown to proceed through an exchange of active centres, a unique phenomenon among proteinaceous enzymes. Furthermore, most recent in vivo studies have revised the roles of transcription accuracy and proofreading factors, as not only required for production of errorless RNAs, but also for prevention of frequent misincorporation-induced pausing that may cause conflicts with fellow RNA polymerases and the replication machinery.}, } @article {pmid28967704, year = {2018}, author = {Bicknell, RDC and Paterson, JR}, title = {Reappraising the early evidence of durophagy and drilling predation in the fossil record: implications for escalation and the Cambrian Explosion.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {754-784}, doi = {10.1111/brv.12365}, pmid = {28967704}, issn = {1469-185X}, abstract = {The Cambrian Explosion is arguably the most extreme example of a biological radiation preserved in the fossil record, and studies of Cambrian Lagerstätten have facilitated the exploration of many facets of this key evolutionary event. As predation was a major ecological driver behind the Explosion - particularly the radiation of biomineralising metazoans - the evidence for shell crushing (durophagy), drilling and puncturing predation in the Cambrian (and possibly the Ediacaran) is considered. Examples of durophagous predation on biomineralised taxa other than trilobites are apparently rare, reflecting predator preference, taphonomic and sampling biases, or simply lack of documentation. The oldest known example of durophagy is shell damage on the problematic taxon Mobergella holsti from the early Cambrian (possibly Terreneuvian) of Sweden. Using functional morphology to identify (or perhaps misidentify) durophagous predators is discussed, with emphasis on the toolkit used by Cambrian arthropods, specifically the radiodontan oral cone and the frontal and gnathobasic appendages of various taxa. Records of drill holes and possible puncture holes in Cambrian shells are mostly on brachiopods, but the lack of prey diversity may represent either a true biological signal or a result of various biases. The oldest drilled Cambrian shells occur in a variety of Terreneuvian-aged taxa, but specimens of the ubiquitous Ediacaran shelly fossil Cloudina also show putative drilling traces. Knowledge on Cambrian shell drillers is sorely lacking and there is little evidence or consensus concerning the taxonomic groups that made the holes, which often leads to the suggestion of an unknown 'soft bodied driller'. Useful methodologies for deciphering the identities and capabilities of shell drillers are outlined. Evidence for puncture holes in Cambrian shelly taxa is rare. Such holes are more jagged than drill holes and possibly made by a Cambrian 'puncher'. The Cambrian arthropod Yohoia may have used its frontal appendages in a jack-knifing manner, similar to Recent stomatopod crustaceans, to strike and puncture shells rapidly. Finally, Cambrian durophagous and shell-drilling predation is considered in the context of escalation - an evolutionary process that, amongst other scenarios, involves predators (and other 'enemies') as the predominant agents of natural selection. The rapid increase in diversity and abundance of biomineralised shells during the early Cambrian is often attributed to escalation: enemies placed selective pressure on prey, forcing phenotypic responses in prey and, by extension, in predator groups over time. Unfortunately, few case studies illustrate long-term patterns in shelly fossil morphologies that may reflect the influence of predation throughout the Cambrian. More studies on phenotypic change in hard-shelled lineages are needed to convincingly illustrate escalation and the responses of prey during the Cambrian.}, } @article {pmid28967236, year = {2018}, author = {Sapp, M and Ploch, S and Fiore-Donno, AM and Bonkowski, M and Rose, LE}, title = {Protists are an integral part of the Arabidopsis thaliana microbiome.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {30-43}, doi = {10.1111/1462-2920.13941}, pmid = {28967236}, issn = {1462-2920}, abstract = {Although protists occupy a vast range of habitats and are known to interact with plants among other things via disease suppression, competition or growth stimulation, their contributions to the 'phytobiome' are not well described. To contribute to a more comprehensive picture of the plant holobiont, we examined cercozoan and oomycete taxa living in association with the model plant Arabidopsis thaliana grown in two different soils. Soil, roots, leaves and wooden toothpicks were analysed before and after surface sterilization. Cercozoa were identified using 18S rRNA gene metabarcoding, whereas the Internal Transcribed Spacer 1 was used to determine oomycetes. Subsequent analyses revealed strong spatial structuring of protist communities between compartments, although oomycetes appeared more specialized than Cercozoa. With regards to oomycetes, only members of the Peronosporales and taxa belonging to the genus Globisporangium were identified as shared members of the A. thaliana microbiome. This also applied to cercozoan taxa belonging to the Glissomonadida and Cercomonadida. We identified a strong influence by edaphic factors on the rhizosphere, but not for the phyllosphere. Distinct differences of Cercozoa found preferably in wood or fresh plant material imply specific niche adaptations. Our results highlight the importance of micro-eukaryotes for the plant holobiont.}, } @article {pmid28967209, year = {2018}, author = {Fazion, F and Perchat, S and Buisson, C and Vilas-Bôas, G and Lereclus, D}, title = {A plasmid-borne Rap-Phr system regulates sporulation of Bacillus thuringiensis in insect larvae.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {145-155}, doi = {10.1111/1462-2920.13946}, pmid = {28967209}, issn = {1462-2920}, abstract = {The entomopathogen Bacillus thuringiensis species harbours numerous plasmids essentially studied for their involvement in pathogenicity, as Cry-plasmids. The life cycle of B. thuringiensis in the insect host is regulated by the sequential activation of quorum sensing systems to kill, survive and sporulate. In this study, we characterize a new quorum sensing system belonging to the Rap-Phr family. The Rap8-Phr8 system is borne by the pHT8_1 plasmid, a small cryptic plasmid from the B. thuringiensis var. kurstaki HD73 strain. Our results demonstrate that the Rap8 protein inhibits sporulation and biofilm formation through the Spo0A pathway. The Rap8 activity is inhibited by the mature Phr8 heptapeptide YAHGKDI. The key residues specific for the Rap phosphatase activity are conserved in Rap8 suggesting a common mode of action. Interestingly, we show that the Rap8-Phr8 system is specifically required for regulating sporulation of B. thuringiensis in insect larvae. This system may allow the bacteria to exert a tight control of the sporulation process in the host cadaver for optimizing the multiplication, the survival and the dissemination of the bacteria. Thus, our results suggest that pHT8_1 provides advantages for adaptation and evolution of B. thuringiensis in its ecological niche.}, } @article {pmid28967193, year = {2018}, author = {De Corte, D and Srivastava, A and Koski, M and Garcia, JAL and Takaki, Y and Yokokawa, T and Nunoura, T and Elisabeth, NH and Sintes, E and Herndl, GJ}, title = {Metagenomic insights into zooplankton-associated bacterial communities.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {492-505}, pmid = {28967193}, issn = {1462-2920}, support = {268595//European Research Council/International ; }, abstract = {Zooplankton and microbes play a key role in the ocean's biological cycles by releasing and consuming copious amounts of particulate and dissolved organic matter. Additionally, zooplankton provide a complex microhabitat rich in organic and inorganic nutrients in which bacteria thrive. In this study, we assessed the phylogenetic composition and metabolic potential of microbial communities associated with crustacean zooplankton species collected in the North Atlantic. Using Illumina sequencing of the 16S rRNA gene, we found significant differences between the microbial communities associated with zooplankton and those inhabiting the surrounding seawater. Metagenomic analysis of the zooplankton-associated microbial community revealed a highly specialized bacterial community able to exploit zooplankton as microhabitat and thus, mediating biogeochemical processes generally underrepresented in the open ocean. The zooplankton-associated bacterial community is able to colonize the zooplankton's internal and external surfaces using a large set of adhesion mechanisms and to metabolize complex organic compounds released or exuded by the zooplankton such as chitin, taurine and other complex molecules. Moreover, the high number of genes involved in iron and phosphorus metabolisms in the zooplankton-associated microbiome suggests that this zooplankton-associated bacterial community mediates specific biogeochemical processes (through the proliferation of specific taxa) that are generally underrepresented in the ambient waters.}, } @article {pmid28967173, year = {2018}, author = {Tong, SM and Zhang, AX and Guo, CT and Ying, SH and Feng, MG}, title = {Daylight length-dependent translocation of VIVID photoreceptor in cells and its essential role in conidiation and virulence of Beauveria bassiana.}, journal = {Environmental microbiology}, volume = {20}, number = {1}, pages = {169-185}, doi = {10.1111/1462-2920.13951}, pmid = {28967173}, issn = {1462-2920}, abstract = {The fungal insect pathogen Beauveria bassiana has the blue-light photoreceptor VIVID (VVD) but lacks a pigmentation pattern to trace its light responses. Here, we show that the fungal vvd is transcriptionally expressed, and linked to other blue/red photoreceptor genes, in a daylight length-dependent manner. GFP-tagged VVD fusion protein was localized to periphery, cytoplasm and vacuoles of hyphal cells in light/dark (L:D) cycles of 24:0 and 16:8 and aggregated in cytoplasm with shortening daylight until transfer into nuclei in full darkness. Deletion of vvd caused more reduced (91%) conidiation capacity in L:D 12:12 cycle of blue light (450/480 nm) than of yellow-to-red (540-760 nm) and white lights (∼70%). The conidiation defect worsened with shortened daylight in different L:D cycles of white light, coinciding well with drastic repression of key activator genes in central development pathway. Intriguingly, the deletion mutant displayed blocked secretion of cuticle-degrading Pr1 proteases, retarded dimorphic transition in insect haemocoel, and hence a lethal action twice longer than those for control strains against Galleria mellonella regardless of the infection passing or bypassing insect cuticle. Conclusively, VVD sustains normal conidiation in a daylight length-dependent manner and acts as a vital virulence factor in B. bassiana.}, } @article {pmid28966124, year = {2018}, author = {Gan, HM and Tan, MH and Lee, YP and Schultz, MB and Horwitz, P and Burnham, Q and Austin, CM}, title = {More evolution underground: Accelerated mitochondrial substitution rate in Australian burrowing freshwater crayfishes (Decapoda: Parastacidae).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {88-98}, doi = {10.1016/j.ympev.2017.09.022}, pmid = {28966124}, issn = {1095-9513}, mesh = {Animals ; Astacoidea/*classification/genetics ; Australia ; Bayes Theorem ; Codon ; DNA/chemistry/isolation & purification/metabolism ; DNA, Mitochondrial/chemistry/classification/*genetics/metabolism ; *Evolution, Molecular ; Fresh Water ; Gene Order ; Likelihood Functions ; Phylogeny ; Sequence Analysis, DNA ; }, abstract = {To further understand the evolutionary history and mitogenomic features of Australia's highly distinctive freshwater crayfish fauna, we utilized a recently described rapid mitogenome sequencing pipeline to generate 24 new crayfish mitogenomes including a diversity of burrowing crayfish species and the first for Astacopsis gouldi, the world's largest freshwater invertebrate. Whole mitogenome-based phylogeny estimates using both Bayesian and Maximum Likelihood methods substantially strengthen existing hypotheses for systematic relationships among Australian freshwater crayfish with evidence of pervasive diversifying selection and accelerated mitochondrial substitution rate among the members of the clade representing strongly burrowing crayfish that may reflect selection pressures for increased energy requirement for adaptation to terrestrial environment and a burrowing lifestyle. Further, gene rearrangements are prevalent in the burrowing crayfish mitogenomes involving both tRNA and protein coding genes. In addition, duplicated control regions were observed in two closely related Engaeus species, together with evidence for concerted evolution. This study significantly adds to the understanding of Australian freshwater crayfish evolutionary relationships and suggests a link between mitogenome evolution and adaptation to terrestrial environments and a burrowing lifestyle in freshwater crayfish.}, } @article {pmid28966123, year = {2018}, author = {Jabbour, F and Gaudeul, M and Lambourdière, J and Ramstein, G and Hassanin, A and Labat, JN and Sarthou, C}, title = {Phylogeny, biogeography and character evolution in the tribe Desmodieae (Fabaceae: Papilionoideae), with special emphasis on the New Caledonian endemic genera.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {108-121}, doi = {10.1016/j.ympev.2017.09.017}, pmid = {28966123}, issn = {1095-9513}, mesh = {Bayes Theorem ; DNA, Chloroplast/genetics ; Ecosystem ; Fabaceae/*classification/genetics ; Fruit/anatomy & histology ; New Caledonia ; Phenotype ; *Phylogeny ; *Phylogeography ; Seeds/anatomy & histology ; Species Specificity ; Time Factors ; }, abstract = {The nearly cosmopolitan tribe Desmodieae (Fabaceae) includes many important genera for medicine and forage. However, the phylogenetic relationships among the infratribal groups circumscribed using morphological traits are still poorly known. In this study, we used chloroplast (rbcL, psbA-trnH) and nuclear (ITS-1) DNA sequences to investigate the molecular phylogeny and historical biogeography of Desmodieae, and infer ancestral states for several vegetative and reproductive traits. Three groups, corresponding to the Desmodium, Lespedeza, and Phyllodium groups sensu Ohashi were retrieved in the phylogenetic analyses. Conflicts in the topologies inferred from the chloroplast and nuclear datasets were detected. For instance, the Lespedeza clade was sister to the groups Phyllodium+Desmodium based on chloroplast DNA, but nested within the Desmodium group based on ITS-1. Moreover, the New Caledonian endemic genera Arthroclianthus and Nephrodesmus were not monophyletic but together formed a clade, which also included Hanslia and Ohwia based on chloroplast DNA. The hypothetical common ancestor of Desmodieae was dated to the Middle Oligocene (ca. 28.3Ma) and was likely an Asian shrub or tree producing indehiscent loments. Several colonization events towards Oceania, America, and Africa occurred (all less than ca. 17.5Ma), most probably through long distance dispersal. The fruits of Desmodieae repeatedly evolved from indehiscence to dehiscence. We also showed that indehiscent loments allow for more variability in the number of seeds per fruit than indehiscent legumes. Modularity seems here to allow variability in the number of ovules produced in a single ovary.}, } @article {pmid28965724, year = {2018}, author = {Commichau, FM and Gibhardt, J and Halbedel, S and Gundlach, J and Stülke, J}, title = {A Delicate Connection: c-di-AMP Affects Cell Integrity by Controlling Osmolyte Transport.}, journal = {Trends in microbiology}, volume = {26}, number = {3}, pages = {175-185}, doi = {10.1016/j.tim.2017.09.003}, pmid = {28965724}, issn = {1878-4380}, mesh = {Bacillus subtilis/metabolism ; Bacterial Proteins ; Cell Membrane/*metabolism ; Cell Wall/metabolism ; Cyclic AMP/*metabolism ; Gram-Positive Bacteria/*metabolism ; Listeria monocytogenes/metabolism ; Membrane Transport Proteins/*metabolism ; Osmoregulation/*physiology ; Phenotype ; Second Messenger Systems ; Staphylococcus aureus/metabolism ; }, abstract = {Bacteria use second-messenger molecules to adapt to their environment. Several second messengers, among them cyclic di-AMP (c-di-AMP), have been discovered and intensively studied. Interestingly, c-di-AMP is essential for growth of Gram-positive bacteria such as Bacillus subtilis, Listeria monocytogenes, and Staphylococcus aureus. Many studies demonstrated that perturbation of c-di-AMP metabolism affects the integrity of the bacterial cell envelope. Therefore, it has been assumed that the nucleotide is essential for proper cell envelope synthesis. In this Opinion paper, we propose that the cell envelope phenotypes caused by perturbations of c-di-AMP metabolism can be interpreted differently: c-di-AMP might indirectly control cell envelope integrity by modulating the turgor, a physical variable that needs to be tightly adjusted. We also discuss open questions related to c-di-AMP metabolism that need to be urgently addressed by future studies.}, } @article {pmid28964886, year = {2018}, author = {Zhuang, Y and Clamp, JC and Yi, Z and Ji, D}, title = {Phylogeny of the families Zoothamniidae and Epistylididae (Protozoa: Ciliophora: Peritrichia) based on analyses of three rRNA-coding regions.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {99-107}, doi = {10.1016/j.ympev.2017.09.023}, pmid = {28964886}, issn = {1095-9513}, mesh = {Base Sequence ; China ; Ciliophora/*classification/genetics ; DNA, Protozoan/genetics ; DNA, Ribosomal/genetics ; Geography ; Likelihood Functions ; Open Reading Frames/*genetics ; *Phylogeny ; RNA, Ribosomal/*genetics ; Ribosome Subunits, Small/genetics ; Species Specificity ; }, abstract = {Peritrichs are a major group of ciliates with worldwide distribution, and they play important roles in many habitats. Intrafamilial phylogeny of some peritrichs was investigated using information from three genes, which provided more robust interpretations than single-gene analyses. Sixty-seven new sequences including SSU rDNA, ITS1-5.8S-ITS2 and LSU rDNA were aligned with available sequences in GenBank to infer phylogenetic relationships within the families Zoothamniidae and Epistylididae. Results reveal the following relationships: (1) Epistylididae is polyphyletic, consisting of two clades that nest within the Zoothamniidae as part of the crown clade of peritrichs (order Vorticellida) and a third one that is part of the basal clade of peritrichs (order Opercularida); (2) Epistylis elongata falls within one of the clades of Zoothamnium rather than with congeners; (3) Zoothamnium is probably paraphyletic, consisting of three divergent clades, with the genera Myoschiston and Zoothamnopsis intermingled with species of Zoothamnium. The following evolutionary hypotheses can be inferred from these results: (1) the contractile stalk of Zoothamnium is plesiomorphic. (2) Myoschiston, Zoothamnopsis and clade II of Epistylididae are derived from the Zoothamnium morphotype by partial or incomplete development of the spasmoneme that forms the contractile center of the stalk around which the rigid cortex is secreted. (3) Clade I of the Epistylididae, which are primarily colonial forms that appear never to have evolved a spasmoneme of any sort, may represent the ancestral morphotype of peritrichs.}, } @article {pmid28963110, year = {2018}, author = {Anderson, DA and Murphy, KM and Briseño, CG}, title = {Development, Diversity, and Function of Dendritic Cells in Mouse and Human.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a028613}, pmid = {28963110}, issn = {1943-0264}, support = {R01 AI076427/AI/NIAID NIH HHS/United States ; }, abstract = {The study of murine dendritic cell (DC) development has been integral to the identification of specialized DC subsets that have unique requirements for their form and function. Advances in the field have also provided a framework for the identification of human DC counterparts, which appear to have conserved mechanisms of development and function. Multiple transcription factors are expressed in unique combinations that direct the development of classical DCs (cDCs), which include two major subsets known as cDC1s and cDC2s, and plasmacytoid DCs (pDCs). pDCs are potent producers of type I interferons and thus these cells are implicated in immune responses that depend on this cytokine. Mouse models deficient in the cDC1 lineage have revealed their importance in directing immune responses to intracellular bacteria, viruses, and cancer through the cross-presentation of cell-associated antigen. Models of transcription factor deficiency have been used to identify subsets of cDC2 that are required for T helper (Th)2 and Th17 responses to certain pathogens; however, no single factor is known to be absolutely required for the development of the complete cDC2 lineage. In this review, we will discuss the current state of knowledge of mouse and human DC development and function and highlight areas in the field that remain unresolved.}, } @article {pmid28963109, year = {2018}, author = {Negishi, H and Taniguchi, T and Yanai, H}, title = {The Interferon (IFN) Class of Cytokines and the IFN Regulatory Factor (IRF) Transcription Factor Family.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a028423}, pmid = {28963109}, issn = {1943-0264}, abstract = {Interferons (IFNs) are a broad class of cytokines elicited on challenge to the host defense and are essential for mobilizing immune responses to pathogens. Divided into three classes, type I, type II, and type III, all IFNs share in common the ability to evoke antiviral activities initiated by the interaction with their cognate receptors. The nine-member IFN regulatory factor (IRF) family, first discovered in the context of transcriptional regulation of type I IFN genes following viral infection, are pivotal for the regulation of the IFN responses. In this review, we briefly describe cardinal features of the three types of IFNs and then focus on the role of the IRF family members in the regulation of each IFN system.}, } @article {pmid28963084, year = {2018}, author = {Bryja, J and Kostin, D and Meheretu, Y and Šumbera, R and Bryjová, A and Kasso, M and Mikula, O and Lavrenchenko, LA}, title = {Reticulate Pleistocene evolution of Ethiopian rodent genus along remarkable altitudinal gradient.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {75-87}, doi = {10.1016/j.ympev.2017.09.020}, pmid = {28963084}, issn = {1095-9513}, mesh = {Animals ; Cytochromes b/chemistry/classification/genetics ; DNA, Mitochondrial/chemistry/isolation & purification/metabolism ; Ecosystem ; Ethiopia ; *Evolution, Molecular ; Haplotypes ; Hybridization, Genetic ; Karyotype ; Murinae/anatomy & histology/*classification/genetics ; Phylogeny ; }, abstract = {The Ethiopian highlands are the most extensive complex of mountainous habitats in Africa. The presence of the Great Rift Valley (GRV) and the striking elevational ecological gradients inhabited by recently radiated Ethiopian endemics, provide a wide spectrum of model situations for evolutionary studies. The extant species of endemic rodents, often markedly phenotypically differentiated, are expected to possess complex genetic features which evolved asa consequence of the interplay between geomorphology and past climatic changes. In this study, we used the largest available multi-locus genetic dataset of the murid genus Stenocephalemys (347 specimens from ca 40 localities across the known distributional area of all taxa) to investigate the relative importance of disruptive selection, temporary geographic isolation and introgression in their adaptive radiations in the Pleistocene. We confirmed the four main highly supported mitochondrial (mtDNA) clades that were proposed as four species in a previous pilot study: S. albipes is a sister species of S. griseicauda (both lineages are present on both sides of the GRV), while the second clade is formed by two Afro-alpine species, S. albocaudata (east of GRV) and the undescribed Stenocephalemys sp. A (west of GRV). There is a clear elevational gradient in the distribution of the Stenocephalemys taxa with two to three species present at different elevations of the same mountain range. Surprisingly, the nuclear species tree corresponded only a little to the mtDNA tree. Multispecies coalescent models based on six nuclear markers revealed the presence of six separate gene pools (i.e. candidate species), with different topology. Phylogenetic analysis, together with the geographic distribution of the genetic groups, suggests a complex reticulate evolution. We propose a scenario that involves (besides classical allopatric speciation) two cases of disruptive selection along the elevational ecological gradient, multiple crosses of GRV in dry and cold periods of the Pleistocene, followed by hybridization and mtDNA introgression on imperfect reproductive barriers. Spatial expansion of the currently most widespread "albipes" mtDNA clade was followed by population fragmentation, lineage sorting and again by hybridization and mtDNA introgression. Comparison of this genetic structure to other Ethiopian endemic taxa highlight the geographical areas of special conservation concern, where more detailed biodiversity studies should be carried out to prevent many endemic taxa from going extinct even before they are recognized.}, } @article {pmid28963083, year = {2018}, author = {Eldridge, RA and Achmadi, AS and Giarla, TC and Rowe, KC and Esselstyn, JA}, title = {Geographic isolation and elevational gradients promote diversification in an endemic shrew on Sulawesi.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {306-317}, doi = {10.1016/j.ympev.2017.09.018}, pmid = {28963083}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; DNA/chemistry/isolation & purification/metabolism ; Gene Flow ; Genetic Variation ; Genetics, Population ; Indonesia ; Islands ; Mitochondria/genetics ; Phylogeny ; Phylogeography ; Sequence Alignment ; Sequence Analysis, DNA ; Shrews/*classification ; }, abstract = {Phylogeographic research on endemic primates and amphibians inhabiting the Indonesian island of Sulawesi revealed the existence of seven areas of endemism (AoEs). Here, we use phylogenetic and population genetic analyses of one mitochondrial gene and 15 nuclear loci to assess geographic patterns of genetic partitioning in a shrew (Crocidura elongata) that is endemic to Sulawesi, but occurs across the island. We uncover substantial genetic diversity in this species both between and within AoEs, but we also identify close relationships between populations residing in different AoEs. One of the earliest divergences within C. elongata distinguishes a high-elevation clade from low-elevation clades. In addition, on one mountain, we observe three distinct genetic groups from low, middle, and high elevations, suggesting divergence along a single elevational gradient. In general, our results show that C. elongata, like several other Sulawesi endemic taxa, harbors extensive genetic diversity. This diversity is structured in part by known AoE boundaries, but also by elevational gradients and geographic isolation within AoEs.}, } @article {pmid28963082, year = {2018}, author = {Heinicke, MP and Lemmon, AR and Lemmon, EM and McGrath, K and Hedges, SB}, title = {Phylogenomic support for evolutionary relationships of New World direct-developing frogs (Anura: Terraranae).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {145-155}, doi = {10.1016/j.ympev.2017.09.021}, pmid = {28963082}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification/*genetics ; *Genomics ; Likelihood Functions ; *Phylogeny ; Sequence Analysis, DNA ; Species Specificity ; }, abstract = {Phylogenomic approaches have proven able to resolve difficult branches in the tree of life. New World direct-developing frogs (Terraranae) represent a large evolutionary radiation in which interrelationships at key points in the phylogeny have not been adequately determined, affecting evolutionary, biogeographic, and taxonomic interpretations. We employed anchored hybrid enrichment to generate a data set containing 389 loci and >600,000 nucleotide positions for 30 terraranan and several outgroup frog species encompassing all major lineages in the clade. Concatenated maximum likelihood and coalescent species-tree approaches recover nearly identical topologies with strong support for nearly all relationships in the tree. These results are similar to previous phylogenetic results but provide additional resolution at short internodes. Among taxa whose placement varied in previous analyses, Ceuthomantis is shown to be the sister taxon to all other terraranans, rather than deeply embedded within the radiation, and Strabomantidae is monophyletic rather than paraphyletic with respect to Craugastoridae. We present an updated taxonomy to reflect these results, and describe a new subfamily for the genus Hypodactylus.}, } @article {pmid28962921, year = {2018}, author = {Law, CJ and Alegre, KO}, title = {Clamping down on drugs: the Escherichia coli multidrug efflux protein MdtM.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {461-467}, doi = {10.1016/j.resmic.2017.09.006}, pmid = {28962921}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/metabolism/pharmacology ; Antiporters/chemistry/genetics/*metabolism ; Biological Transport ; Drug Resistance, Multiple, Bacterial ; Escherichia coli/chemistry/drug effects/genetics/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Multigene Family ; }, abstract = {Multidrug resistance is principally a consequence of the active transport of drugs out of the cell by proteins that are integral membrane transporters. In the following review, we present a synthesis of current understanding of the Escherichia coli multidrug resistance transporter, MdtM, a 410 amino acid residue protein that belongs to the large and ubiquitous major facilitator superfamily (MFS).}, } @article {pmid28961885, year = {2018}, author = {Houot, B and Cazalé-Debat, L and Fraichard, S and Everaerts, C and Saxena, N and Sane, SP and Ferveur, JF}, title = {Gene Regulation and Species-Specific Evolution of Free Flight Odor Tracking in Drosophila.}, journal = {Molecular biology and evolution}, volume = {35}, number = {1}, pages = {3-15}, doi = {10.1093/molbev/msx241}, pmid = {28961885}, issn = {1537-1719}, abstract = {The flying ability of insects has coevolved with the development of organs necessary to take-off from the ground, generate, and modulate lift during flight in complex environments. Flight orientation to the appropriate food source and mating partner depends on the perception and integration of multiple chemical signals. We used a wind tunnel-based assay to investigate the natural and molecular evolution of free flight odor tracking in Drosophila. First, the comparison of female and male flies of several populations and species revealed substantial sex-, inter-, and intra-specific variations for distinct flight features. In these flies, we compared the molecular structure of desat1, a fast-evolving gene involved in multiple aspects of Drosophila pheromonal communication. We manipulated desat1 regulation and found that both neural and nonneural tissues affect distinct flight features. Together, our data suggest that desat1 is one of the genes involved in the evolution of free-flight odor tracking behaviors in Drosophila.}, } @article {pmid28961452, year = {2018}, author = {Baidya, AK and Bhattacharya, S and Dubey, GP and Mamou, G and Ben-Yehuda, S}, title = {Bacterial nanotubes: a conduit for intercellular molecular trade.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {1-6}, doi = {10.1016/j.mib.2017.08.006}, pmid = {28961452}, issn = {1879-0364}, mesh = {Animals ; Bacillus/physiology ; Bacteria/*cytology/metabolism ; *Bacterial Physiological Phenomena ; Biological Transport ; Cell Communication ; Cell Membrane/physiology ; Cytoplasm/physiology ; Humans ; Microbial Interactions/physiology ; *Nanotubes ; }, abstract = {Bacteria use elaborate molecular machines for intercellular contact-dependent interactions. We discuss a relatively less explored type of intercellular connections mediated by tubular membranous bridges, termed nanotubes. Increasing evidence suggests that nanotube structures mediate cytoplasmic molecular trade among neighboring cells of the same and different species. Further, nanotubes were found to facilitate both antagonistic and cooperative interspecies interactions, thereby allowing the emergence of new non-heritable phenotypes in multicellular bacterial communities. We propose that nanotube-mediated cytoplasmic sharing represents a widespread form of bacterial interactions in nature, providing an enormous potential for the emergence of new features. Here we review the current knowledge on bacterial nanotubes, and highlight the gaps in our current understanding of their operation.}, } @article {pmid28961073, year = {2018}, author = {Levin, LA}, title = {Manifestation, Drivers, and Emergence of Open Ocean Deoxygenation.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {229-260}, doi = {10.1146/annurev-marine-121916-063359}, pmid = {28961073}, issn = {1941-0611}, abstract = {Oxygen loss in the ocean, termed deoxygenation, is a major consequence of climate change and is exacerbated by other aspects of global change. An average global loss of 2% or more has been recorded in the open ocean over the past 50-100 years, but with greater oxygen declines in intermediate waters (100-600 m) of the North Pacific, the East Pacific, tropical waters, and the Southern Ocean. Although ocean warming contributions to oxygen declines through a reduction in oxygen solubility and stratification effects on ventilation are reasonably well understood, it has been a major challenge to identify drivers and modifying factors that explain different regional patterns, especially in the tropical oceans. Changes in respiration, circulation (including upwelling), nutrient inputs, and possibly methane release contribute to oxygen loss, often indirectly through stimulation of biological production and biological consumption. Microbes mediate many feedbacks in oxygen minimum zones that can either exacerbate or ameliorate deoxygenation via interacting nitrogen, sulfur, and carbon cycles. The paleo-record reflects drivers of and feedbacks to deoxygenation that have played out through the Phanerozoic on centennial, millennial, and hundred-million-year timescales. Natural oxygen variability has made it difficult to detect the emergence of a climate-forced signal of oxygen loss, but new modeling efforts now project emergence to occur in many areas in 15-25 years. Continued global deoxygenation is projected for the next 100 or more years under most emissions scenarios, but with regional heterogeneity. Notably, even small changes in oxygenation can have significant biological effects. New efforts to systematically observe oxygen changes throughout the open ocean are needed to help address gaps in understanding of ocean deoxygenation patterns and drivers.}, } @article {pmid28961072, year = {2018}, author = {Lehahn, Y and d'Ovidio, F and Koren, I}, title = {A Satellite-Based Lagrangian View on Phytoplankton Dynamics.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {99-119}, doi = {10.1146/annurev-marine-121916-063204}, pmid = {28961072}, issn = {1941-0611}, abstract = {The well-lit upper layer of the open ocean is a dynamical environment that hosts approximately half of global primary production. In the remote parts of this environment, distant from the coast and from the seabed, there is no obvious spatially fixed reference frame for describing the dynamics of the microscopic drifting organisms responsible for this immense production of organic matter-the phytoplankton. Thus, a natural perspective for studying phytoplankton dynamics is to follow the trajectories of water parcels in which the organisms are embedded. With the advent of satellite oceanography, this Lagrangian perspective has provided valuable information on different aspects of phytoplankton dynamics, including bloom initiation and termination, spatial distribution patterns, biodiversity, export of carbon to the deep ocean, and, more recently, bottom-up mechanisms that affect the distribution and behavior of higher-trophic-level organisms. Upcoming submesoscale-resolving satellite observations and swarms of autonomous platforms open the way to the integration of vertical dynamics into the Lagrangian view of phytoplankton dynamics.}, } @article {pmid28961071, year = {2018}, author = {Hostetler, CA and Behrenfeld, MJ and Hu, Y and Hair, JW and Schulien, JA}, title = {Spaceborne Lidar in the Study of Marine Systems.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {121-147}, doi = {10.1146/annurev-marine-121916-063335}, pmid = {28961071}, issn = {1941-0611}, abstract = {Satellite passive ocean color instruments have provided an unbroken ∼20-year record of global ocean plankton properties, but this measurement approach has inherent limitations in terms of spatial-temporal sampling and ability to resolve vertical structure within the water column. These limitations can be addressed by coupling ocean color data with measurements from a spaceborne lidar. Airborne lidars have been used for decades to study ocean subsurface properties, but recent breakthroughs have now demonstrated that plankton properties can be measured with a satellite lidar. The satellite lidar era in oceanography has arrived. Here, we present a review of the lidar technique, its applications in marine systems, a perspective on what can be accomplished in the near future with an ocean- and atmosphere-optimized satellite lidar, and a vision for a multiplatform virtual constellation of observational assets that would enable a three-dimensional reconstruction of global ocean ecosystems.}, } @article {pmid28958602, year = {2018}, author = {Lustigman, S and Makepeace, BL and Klei, TR and Babayan, SA and Hotez, P and Abraham, D and Bottazzi, ME}, title = {Onchocerca volvulus: The Road from Basic Biology to a Vaccine.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {64-79}, pmid = {28958602}, issn = {1471-5007}, support = {R01 AI078314/AI/NIAID NIH HHS/United States ; }, mesh = {Animals ; Antiparasitic Agents/pharmacology/standards/therapeutic use ; Drug Resistance ; Humans ; Onchocerca volvulus/drug effects ; Onchocerciasis, Ocular/drug therapy/immunology/*prevention & control/transmission ; *Vaccines ; }, abstract = {Human onchocerciasis - commonly known as river blindness - is one of the most devastating yet neglected tropical diseases, leaving many millions in sub-Saharan Africa blind and/or with chronic disabilities. Attempts to eliminate onchocerciasis, primarily through the mass drug administration of ivermectin, remains challenging and has been heightened by the recent news that drug-resistant parasites are developing in some populations after years of drug treatment. Needed, and needed now, in the fight to eliminate onchocerciasis are new tools, such as preventive and therapeutic vaccines. This review summarizes the progress made to advance the onchocerciasis vaccine from the research laboratory into the clinic.}, } @article {pmid28957710, year = {2018}, author = {Wolf, T and Kämmer, P and Brunke, S and Linde, J}, title = {Two's company: studying interspecies relationships with dual RNA-seq.}, journal = {Current opinion in microbiology}, volume = {42}, number = {}, pages = {7-12}, doi = {10.1016/j.mib.2017.09.001}, pmid = {28957710}, issn = {1879-0364}, mesh = {Computational Biology ; Gene Expression Profiling ; High-Throughput Nucleotide Sequencing/methods ; Host-Pathogen Interactions/*genetics ; Humans ; Microbial Interactions/*genetics ; RNA/*analysis/metabolism ; Sequence Analysis, RNA/*methods ; Transcriptome ; }, abstract = {Organisms do not exist isolated from each other, but constantly interact. Cells can sense the presence of interaction partners by a range of receptors and, via complex regulatory networks, specifically react by changing the expression of many of their genes. Technological advances in next-generation sequencing over the recent years now allow us to apply RNA sequencing to two species at the same time (dual RNA-seq), and thus to directly study the gene expression of two interacting species without the need to physically separate cells or RNA. In this review, we give an overview over the latest studies in interspecies interactions made possible by dual RNA-seq, ranging from pathogenic to symbiotic relationships. We summarize state-of-the-art experimental techniques, bioinformatic data analysis and data interpretation, while also highlighting potential problems and pitfalls starting from the selection of meaningful time points and number of reads to matters of rRNA depletion. A short outlook on new trends in the field of dual RNA-seq concludes this review, looking at sequencing of non-coding RNAs during host-pathogen interactions and the prediction of molecular interspecies interactions networks.}, } @article {pmid28956106, year = {2018}, author = {Li, WW and Xia, MS and Li, WB and Liu, LW and Yang, Y and Li, JH}, title = {Characterization of a Putative S-layer Protein of a Colonial Microcystis Strain.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {173-178}, pmid = {28956106}, issn = {1432-0991}, support = {31370217//The National Natural Science Foundation of China/ ; PAPD//the project of Priority Academic Program Development of Jiangsu Higher Education Institutions/ ; }, mesh = {Bacterial Proteins/*analysis/genetics ; Cell Wall/*chemistry ; DNA, Bacterial/chemistry/genetics ; Electrophoresis, Polyacrylamide Gel ; Membrane Glycoproteins/*analysis/genetics ; Microcystis/*chemistry ; Molecular Weight ; Sequence Analysis, DNA ; Sequence Homology ; }, abstract = {Cell surface structure plays a key role in Microcystis colony formation. The S-layer is a crystalline array of monomolecular proteins that constitute the outermost component of the cyanobacterial cell envelope. To date, no biochemical characterization of the S-layer protein in Microcystis has been reported. Here, we compared S-layer on the cell wall of the unicellular strain Microcystis aeruginosa PCC7806 with the colonial strain M. aeruginosa XW01. We observed crystalline S-layers in XW01 cell walls; however, similar structures were not observed in PCC7806. Sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis revealed a thick putative S-layer protein band with an apparent molecular weight of 70 kDa extracted from XW01 cells, as well as an S-layer peptide fragment with the sequence ETYPLLAAPGAATDATR, similar to the translated product from PCC7806 unknown gene CAO89090.1. The amino acid composition of the translated CAO89090.1 product shared biochemical characteristics with those of bacterial S-layer proteins. Furthermore, a 1002-bp DNA fragment amplified from XW01 displayed 95% similarity with the CAO89090.1 gene, while the S-layer gene expression in XW01 was 36-fold higher than that observed in PCC7806. These data suggested that the S-layer protein plays a key role in Microcystis colony formation due to its significant contribution to cell surface hydrophobicity.}, } @article {pmid28951254, year = {2018}, author = {Palanisamy, N and Akaberi, D and Lennerstrand, J}, title = {Protein backbone flexibility pattern is evolutionarily conserved in the Flaviviridae family: A case of NS3 protease in Flavivirus and Hepacivirus.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {58-63}, doi = {10.1016/j.ympev.2017.09.015}, pmid = {28951254}, issn = {1095-9513}, mesh = {Amino Acid Sequence ; Animals ; *Evolution, Molecular ; Flavivirus/*enzymology ; Hepacivirus/*enzymology ; Humans ; Likelihood Functions ; Phylogeny ; Protein Structure, Tertiary ; RNA Helicases/chemistry/classification/genetics ; Sequence Alignment ; Serine Endopeptidases/chemistry/classification/genetics ; Viral Nonstructural Proteins/chemistry/*classification/genetics ; }, abstract = {Viruses belonging to the Flaviviridae family have been an important health concern for humans, animals and birds alike. No specific treatment is available yet for many of the viral infections caused by the members of this family. Lack of specific drugs against these viruses is mainly due to lack of protein structure information. It has been known that protein backbone fluctuation pattern is highly conserved in protein pairs with similar folds, in spite of the lack of sequence similarity. We hypothesized that this concept should also hold true for proteins (especially enzymes) of viruses included in different genera of the Flaviviridae family, as we know that the sequence similarity between them is low. Using available NS3 protease crystal structures of the Flaviviridae family, our preliminary results have shown that the Cα (i.e. backbone) fluctuation patterns are highly similar between Flaviviruses and a Hepacivirus (i.e. hepatitis C virus, HCV). This has to be validated further experimentally.}, } @article {pmid28951253, year = {2018}, author = {Musher, LJ and Cracraft, J}, title = {Phylogenomics and species delimitation of a complex radiation of Neotropical suboscine birds (Pachyramphus).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {204-221}, doi = {10.1016/j.ympev.2017.09.013}, pmid = {28951253}, issn = {1095-9513}, mesh = {Animals ; Argentina ; Base Sequence ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Genetic Loci ; *Genomics ; Likelihood Functions ; Mexico ; Passeriformes/*classification/*genetics ; *Phylogeny ; Phylogeography ; Species Specificity ; *Tropical Climate ; }, abstract = {Phylogeographic studies within the Neotropics continue to uncover hidden diversity, the extent of which remains poorly known. In birds, molecular studies are producing evidence that species-level diversity is substantially underestimated. Many avian taxa comprise large complexes of subspecies that often represent species-level taxa by various criteria. One such group of Neotropical suboscine birds, the becards (Pachyramphus), ranges from Argentina through northern Mexico. Their taxonomic limits have been complex and controversial as the genus has bounced around a number of suboscine families. Additionally, the phylogenetic relationships within Pachyramphus are unresolved due to insufficient sampling of taxa and populations across species' ranges. We used target capture of ultraconserved elements for 62 individuals representing 42 taxa, and sequenced two mitochondrial genes and two nuclear introns covering 265 individuals of 51 taxa, including all recognized species, resulting in the most densely and completely sampled phylogenetic hypothesis for Pachyramphus to date. We delimited species using a traditional taxonomic approach and then tested them under a Bayesian multi-species coalescent framework. In doing so, we provide evidence for multiple young, previously undetected evolutionary lineages within Pachyramphus. Deep, well-supported branches and a high number of intraspecific lineages across the tree suggest that at least 50% of species diversity may be unrecognized.}, } @article {pmid28951231, year = {2018}, author = {Yardeni, EH and Zomot, E and Bibi, E}, title = {The fascinating but mysterious mechanistic aspects of multidrug transport by MdfA from Escherichia coli.}, journal = {Research in microbiology}, volume = {169}, number = {7-8}, pages = {455-460}, doi = {10.1016/j.resmic.2017.09.004}, pmid = {28951231}, issn = {1769-7123}, mesh = {Anti-Bacterial Agents/*metabolism/pharmacology ; Biological Transport ; Drug Resistance, Multiple, Bacterial ; Escherichia coli/chemistry/drug effects/genetics/*metabolism ; Escherichia coli Proteins/chemistry/genetics/*metabolism ; Membrane Transport Proteins/chemistry/genetics/*metabolism ; }, abstract = {MdfA is an interesting member of a large group of secondary multidrug (Mdr) transporters. Through genetic, biochemical and biophysical studies of MdfA, many challenging aspects of the multidrug transport phenomenon have been addressed. This includes its ability to interact with chemically unrelated drugs and how it utilizes energy to drive efflux of compounds that are not only structurally, but also electrically, different. Admittedly, however, despite all efforts and a recent pioneering structural contribution, several important mechanistic issues of the promiscuous capabilities of MdfA still seek better molecular and dynamic understanding.}, } @article {pmid28951230, year = {2018}, author = {Colin, Y and Gury, J and Monperrus, M and Gentes, S and Ayala Borda, P and Goni-Urriza, M and Guyoneaud, R}, title = {Biosensor for screening bacterial mercury methylation: example within the Desulfobulbaceae.}, journal = {Research in microbiology}, volume = {169}, number = {1}, pages = {44-51}, doi = {10.1016/j.resmic.2017.09.005}, pmid = {28951230}, issn = {1769-7123}, mesh = {Biosensing Techniques ; Desulfovibrio/classification/genetics/isolation & purification/*metabolism ; Geologic Sediments/microbiology ; Mercury/chemistry/*metabolism ; Methylation ; Phylogeny ; Sulfates/metabolism ; Sulfides/metabolism ; }, abstract = {Mercury methylation and demethylation processes govern the fate of methylmercury in aquatic ecosystems. Under anoxic conditions, methylation activity is mainly of biological origin and is often the result of sulfate-reducing bacteria. In this study, the use of a luminescent biosensor for screening methylmercury production was validated by exposing the reporter strain to methylating or non-methylating Desulfovibrio strains. The sensitivity of the biosensor to methylmercury was shown to depend on sulfate-reducing bacterial growth conditions. Bioluminescence was measured using 1-10 mM of sulfides. As the sulfide level increased, luminescence decreased by 40-70%, respectively. Nevertheless, assuming an average of 5 mM of sulfide produced during sulfate-reducing growth, a mercury methylation potential of over 4% was detected when using 185 nM of inorganic mercury. Due to technical limitations, mercury speciation has, to date, only been investigated in a small number of bacterial strains, and no consistent phylogenetic distribution has been identified. Here, the biosensor was further used to assess the Hg methylation capacities of an additional 21 strains related to the Desulfobulbaceae. Seven of them were identified as methylmercury producers. Cultivation procedures combined with bacterial biosensors could provide innovative tools to identify new methylator clades amongst the prokaryotes.}, } @article {pmid28951191, year = {2018}, author = {Zhang, L and Zhang, LB}, title = {Phylogeny and systematics of the brake fern genus Pteris (Pteridaceae) based on molecular (plastid and nuclear) and morphological evidence.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {265-285}, doi = {10.1016/j.ympev.2017.09.011}, pmid = {28951191}, issn = {1095-9513}, mesh = {Antarctic Regions ; Base Composition ; Base Sequence ; Cell Nucleus/genetics ; Phylogeny ; Plant Proteins/classification/genetics/metabolism ; Plastids/classification/genetics ; Pteridaceae/*classification/genetics ; Sequence Alignment ; }, abstract = {The brake fern genus Pteris belongs to Pteridaceae subfamily Pteridoideae. It is one of the largest fern genera and has been estimated to contain 200-250 species distributed on all continents except Antarctica. Previous studies were either based on plastid data only or based on both plastid and nuclear data but the sampling was small. In addition, an infrageneric classification of Pteris based on morphological and molecular evidence has not been available yet. In the present study, based on molecular data of eight plastid markers and one nuclear marker (gapCp) of 256 accessions representing ca. 178 species of Pteris, we reconstruct a global phylogeny of Pteris. The 15 major clades identified earlier are recovered here and we further identified a new major clade. Our nuclear phylogeny recovered 11 of these 16 major clades, seven of which are strongly supported. The inclusion of Schizostege in Pteris is confirmed for the first time. Based on the newly reconstructed phylogeny and evidence from morphology, distribution and/or ecology, we classify Pteris into three subgenera: P. subg. Pteris, P. subg. Campteria, and P. subg. Platyzoma. The former two are further divided into three and 12 sections, respectively.}, } @article {pmid28944555, year = {2018}, author = {Congreve, CR and Falk, AR and Lamsdell, JC}, title = {Biological hierarchies and the nature of extinction.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {811-826}, doi = {10.1111/brv.12368}, pmid = {28944555}, issn = {1469-185X}, abstract = {Hierarchy theory recognises that ecological and evolutionary units occur in a nested and interconnected hierarchical system, with cascading effects occurring between hierarchical levels. Different biological disciplines have routinely come into conflict over the primacy of different forcing mechanisms behind evolutionary and ecological change. These disconnects arise partly from differences in perspective (with some researchers favouring ecological forcing mechanisms while others favour developmental/historical mechanisms), as well as differences in the temporal framework in which workers operate. In particular, long-term palaeontological data often show that large-scale (macro) patterns of evolution are predominantly dictated by shifts in the abiotic environment, while short-term (micro) modern biological studies stress the importance of biotic interactions. We propose that thinking about ecological and evolutionary interactions in a hierarchical framework is a fruitful way to resolve these conflicts. Hierarchy theory suggests that changes occurring at lower hierarchical levels can have unexpected, complex effects at higher scales due to emergent interactions between simple systems. In this way, patterns occurring on short- and long-term time scales are equally valid, as changes that are driven from lower levels will manifest in different forms at higher levels. We propose that the dual hierarchy framework fits well with our current understanding of evolutionary and ecological theory. Furthermore, we describe how this framework can be used to understand major extinction events better. Multi-generational attritional loss of reproductive fitness (MALF) has recently been proposed as the primary mechanism behind extinction events, whereby extinction is explainable solely through processes that result in extirpation of populations through a shutdown of reproduction. While not necessarily explicit, the push to explain extinction through solely population-level dynamics could be used to suggest that environmentally mediated patterns of extinction or slowed speciation across geological time are largely artefacts of poor preservation or a coarse temporal scale. We demonstrate how MALF fits into a hierarchical framework, showing that MALF can be a primary forcing mechanism at lower scales that still results in differential survivorship patterns at the species and clade level which vary depending upon the initial environmental forcing mechanism. Thus, even if MALF is the primary mechanism of extinction across all mass extinction events, the primary environmental cause of these events will still affect the system and result in differential responses. Therefore, patterns at both temporal scales are relevant.}, } @article {pmid28943376, year = {2018}, author = {Kishida, T and Suzuki, M and Takayama, A}, title = {Evolution of the alternative AQP2 gene: Acquisition of a novel protein-coding sequence in dolphins.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {54-57}, doi = {10.1016/j.ympev.2017.09.012}, pmid = {28943376}, issn = {1095-9513}, mesh = {Alternative Splicing ; Animals ; Aquaporin 2/*chemistry/genetics/metabolism ; Base Sequence ; Dolphins/*classification/metabolism ; *Evolution, Molecular ; Exons ; Introns ; Kidney/metabolism ; Phylogeny ; Protein Isoforms/chemistry/genetics/metabolism ; RNA/chemistry/isolation & purification/metabolism ; Sequence Alignment ; Sequence Analysis, DNA ; }, abstract = {Taxon-specific de novo protein-coding sequences are thought to be important for taxon-specific environmental adaptation. A recent study revealed that bottlenose dolphins acquired a novel isoform of aquaporin 2 generated by alternative splicing (alternative AQP2), which helps dolphins to live in hyperosmotic seawater. The AQP2 gene consists of four exons, but the alternative AQP2 gene lacks the fourth exon and instead has a longer third exon that includes the original third exon and a part of the original third intron. Here, we show that the latter half of the third exon of the alternative AQP2 arose from a non-protein-coding sequence. Intact ORF of this de novo sequence is shared not by all cetaceans, but only by delphinoids. However, this sequence is conservative in all modern cetaceans, implying that this de novo sequence potentially plays important roles for marine adaptation in cetaceans.}, } @article {pmid28943375, year = {2018}, author = {Emerling, CA}, title = {Independent pseudogenization of CYP2J19 in penguins, owls and kiwis implicates gene in red carotenoid synthesis.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {47-53}, doi = {10.1016/j.ympev.2017.09.016}, pmid = {28943375}, issn = {1095-9513}, mesh = {Animals ; Base Sequence ; Birds/*classification/genetics ; Carotenoids/*biosynthesis ; Cytochrome P-450 Enzyme System/classification/*genetics ; Databases, Genetic ; Evolution, Molecular ; Phylogeny ; Retina/metabolism ; Spheniscidae/*classification/metabolism ; Strigiformes/*classification/metabolism ; }, abstract = {Carotenoids have important roles in bird behavior, including pigmentation for sexual signaling and improving color vision via retinal oil droplets. Yellow carotenoids are diet-derived, but red carotenoids (ketocarotenoids) are typically synthesized from yellow precursors via a carotenoid ketolase. Recent research on passerines has provided evidence that a cytochrome p450 enzyme, CYP2J19, is responsible for this reaction, though it is unclear if this function is phylogenetically restricted. Here I provide evidence that CYP2J19 is the carotenoid ketolase common to Aves using the genomes of 65 birds and the retinal transcriptomes of 15 avian taxa. CYP2J19 is functionally intact and robustly transcribed in all taxa except for several species adapted to foraging in dim light conditions. Two penguins, an owl and a kiwi show evidence of genetic lesions and relaxed selection in their genomic copy of CYP2J19, and six owls show evidence of marked reduction in CYP2J19 retinal transcription compared to nine diurnal avian taxa. Furthermore, one of the owls appears to transcribe a CYP2J19 pseudogene. Notably, none of these taxa are known to use red carotenoids for sexual signaling and several species of owls and penguins represent the only birds known to completely lack red retinal oil droplets. The remaining avian taxa belong to groups known to possess red oil droplets, are known or expected to deposit red carotenoids in skin and/or plumage, and/or frequently forage in bright light. The loss and reduced expression of CYP2J19 is likely an adaptation to maximize retinal sensitivity, given that oil droplets reduce the amount of light available to the retina.}, } @article {pmid28942015, year = {2018}, author = {Chen, P and Wang, H and Tao, Z and Xu, A and Lin, X and Zhou, N and Wang, P and Wang, Q}, title = {Multiple transmission chains of coxsackievirus A4 co-circulating in China and neighboring countries in recent years: Phylogenetic and spatiotemporal analyses based on virological surveillance.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {23-31}, doi = {10.1016/j.ympev.2017.09.014}, pmid = {28942015}, issn = {1095-9513}, mesh = {Asia ; Bayes Theorem ; Capsid Proteins/chemistry/genetics ; China ; Coxsackievirus Infections/diagnosis/transmission/virology ; Enterovirus/*classification/genetics ; Europe ; Humans ; Molecular Typing ; Phylogeny ; Phylogeography ; RNA, Viral/isolation & purification/metabolism ; Spatio-Temporal Analysis ; }, abstract = {Coxsackievirus A4 (CV-A4) has been reported frequently in association with many infectious diseases and cases of hand, foot, and mouth disease potentially associated with CV-A4 infection are also identified. This study summarized the Shandong CV-A4 strains isolated from 25years acute flaccid paralysis surveillance, with an emphasis on exploring the phylogenetic analyses and spatiotemporal dynamics of CV-A4 at the global scale. We sampled 43 CV-A4 isolates and utilized VP1 gene to construct phylogenetic trees. Further extensive Bayesian phylogeographic analysis was carried out to investigate the evolution of CV-A4 and understand the spatiotemporal diffusion around the world using BEAST and SPREAD software. Phylogenetic trees showed that CV-A4 emerged to be more active in recent decades and multiple transmission chains were co-circulating. The molecular clock analysis estimated a mean evolutionary rate of 6.4×10-3 substitutions/site/year, and the estimated origin of CV-A4 around 1944. The phylogeographic analyses suggested the origin of CV-A4 could be in the USA, however regional dissemination was mainly located around the Asia-Europe region. The spatiotemporal dynamics of CV-A4 exhibited frequent viral traffic among localities, and virus from Shandong province seemed to have played a central role in spreading around China and neighboring countries. Our phylogenetic description and phylogeographic analyses indicate the importance of large spatial- and temporal-scale studies in understanding epidemiological dynamics of CV-A4, particularly the diffusion routes will be of great importance to global control efforts.}, } @article {pmid28941124, year = {2018}, author = {Pellissier, L and Albouy, C and Bascompte, J and Farwig, N and Graham, C and Loreau, M and Maglianesi, MA and Melián, CJ and Pitteloud, C and Roslin, T and Rohr, R and Saavedra, S and Thuiller, W and Woodward, G and Zimmermann, NE and Gravel, D}, title = {Comparing species interaction networks along environmental gradients.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {785-800}, doi = {10.1111/brv.12366}, pmid = {28941124}, issn = {1469-185X}, abstract = {Knowledge of species composition and their interactions, in the form of interaction networks, is required to understand processes shaping their distribution over time and space. As such, comparing ecological networks along environmental gradients represents a promising new research avenue to understand the organization of life. Variation in the position and intensity of links within networks along environmental gradients may be driven by turnover in species composition, by variation in species abundances and by abiotic influences on species interactions. While investigating changes in species composition has a long tradition, so far only a limited number of studies have examined changes in species interactions between networks, often with differing approaches. Here, we review studies investigating variation in network structures along environmental gradients, highlighting how methodological decisions about standardization can influence their conclusions. Due to their complexity, variation among ecological networks is frequently studied using properties that summarize the distribution or topology of interactions such as number of links, connectance, or modularity. These properties can either be compared directly or using a procedure of standardization. While measures of network structure can be directly related to changes along environmental gradients, standardization is frequently used to facilitate interpretation of variation in network properties by controlling for some co-variables, or via null models. Null models allow comparing the deviation of empirical networks from random expectations and are expected to provide a more mechanistic understanding of the factors shaping ecological networks when they are coupled with functional traits. As an illustration, we compare approaches to quantify the role of trait matching in driving the structure of plant-hummingbird mutualistic networks, i.e. a direct comparison, standardized by null models and hypothesis-based metaweb. Overall, our analysis warns against a comparison of studies that rely on distinct forms of standardization, as they are likely to highlight different signals. Fostering a better understanding of the analytical tools available and the signal they detect will help produce deeper insights into how and why ecological networks vary along environmental gradients.}, } @article {pmid28941010, year = {2018}, author = {Baudier, J}, title = {ATAD3 proteins: brokers of a mitochondria-endoplasmic reticulum connection in mammalian cells.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {827-844}, doi = {10.1111/brv.12373}, pmid = {28941010}, issn = {1469-185X}, abstract = {In yeast, a sequence of physical and genetic interactions termed the endoplasmic reticulum (ER)-mitochondria organizing network (ERMIONE) controls mitochondria-ER interactions and mitochondrial biogenesis. Several functions that characterize ERMIONE complexes are conserved in mammalian cells, suggesting that a similar tethering complex must exist in metazoans. Recent studies have identified a new family of nuclear-encoded ATPases associated with diverse cellular activities (AAA+-ATPase) mitochondrial membrane proteins specific to multicellular eukaryotes, called the ATPase family AAA domain-containing protein 3 (ATAD3) proteins (ATAD3A and ATAD3B). These proteins are crucial for normal mitochondrial-ER interactions and lie at the heart of processes underlying mitochondrial biogenesis. ATAD3A orthologues have been studied in flies, worms, and mammals, highlighting the widespread importance of this gene during embryonic development and in adulthood. ATAD3A is a downstream effector of target of rapamycin (TOR) signalling in Drosophila and exhibits typical features of proteins from the ERMIONE-like complex in metazoans. In humans, mutations in the ATAD3A gene represent a new link between altered mitochondrial-ER interaction and recognizable neurological syndromes. The primate-specific ATAD3B protein is a biomarker of pluripotent embryonic stem cells. Through negative regulation of ATAD3A function, ATAD3B supports mitochondrial stemness properties.}, } @article {pmid28940107, year = {2018}, author = {Huang, X and Zhang, H and Chen, F and Song, M}, title = {Colonization of Paracoccus sp. QCT6 and Enhancement of Metribuzin Degradation in Maize Rhizosphere Soil.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {156-162}, pmid = {28940107}, issn = {1432-0991}, support = {41671317//National Natural Science Fund of China/ ; KYZ201635//Fundamental Research Funds for the Central Universities/ ; }, mesh = {Bacterial Typing Techniques ; Biotransformation ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Herbicides/*metabolism ; Paracoccus/classification/genetics/isolation & purification/*metabolism ; Phylogeny ; Plant Roots/microbiology ; RNA, Ribosomal, 16S/genetics ; *Rhizosphere ; Sequence Analysis, DNA ; Soil Pollutants/*metabolism ; Triazines/*metabolism ; Zea mays/growth & development/*microbiology ; }, abstract = {Strain QCT6, capable of degrading metribuzin, was isolated from metribuzin-contaminated soil. The isolate was identified as Paracoccus sp. according to its physiological characteristics, biochemical tests, and 16S rRNA gene phylogenetic analysis. In liquid culture, 86.4% of 50 mg/L metribuzin was removed by strain QCT6 after incubation for 7 days. The product of metribuzin degradation by QCT6 was identified as deamino-metribuzin, which has reduced phytotoxicity on the growth of maize. After being marked with the gfp gene, the colonization and distribution of gfp-tagged QCT6 were directly observed with a confocal laser scanning microscope. The QCT6 strain showed good colonization ability on maize roots and was maintained for at least 20 days in rhizosphere soil. After root irrigation with gfp-tagged QCT6, 75.7% of 15 mg/L metribuzin was removed from the maize rhizosphere soil. This metribuzin-degrading strain QCT6 has strong potential applications for in situ bioremediation of soil contaminated with metribuzin.}, } @article {pmid28940091, year = {2018}, author = {Charnock, C and Samuelsen, Ø and Nordlie, AL and Hjeltnes, B}, title = {Use of a Commercially Available Microarray to Characterize Antibiotic-Resistant Clinical Isolates of Klebsiella pneumoniae.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {163-172}, pmid = {28940091}, issn = {1432-0991}, mesh = {Disk Diffusion Antimicrobial Tests ; *Drug Resistance, Bacterial ; Genotyping Techniques/*methods ; Humans ; Klebsiella Infections/*microbiology ; Klebsiella pneumoniae/drug effects/*genetics/isolation & purification ; Microarray Analysis/*methods ; }, abstract = {A commercially available microarray (IDENTIBAC AMR-ve) for the detection of antibiotic resistance determinants was investigated for its potential to genotype 30 clinical isolates and two control strains of Klebsiella pneumoniae. Resistance profiles and the production of extended-spectrum β-lactamases were determined by disc diffusion and the results were compared with the microarray profiles in order to assess its scope and limitations. Genes associated with resistance to a wide range of antibiotics, including current first line therapy options, were detected. In addition, the array also detected class 1 integrases. The array is easy to use and interpret, and is useful in providing a general description of the numbers and types of resistance determinants in K. pneumoniae. It also provides an indication of the potential for resistance gene acquisition. However, in most instances detected resistance to specific antibiotics could not unequivocally be assigned to hybridization with a specific array probe. We conclude that the microarray is a valuable and rapid means of investigating the presence of resistance gene classes of therapeutic importance. It can also provide a starting point for selecting analyses of greater resolving power, such as phylogenetic subtyping by PCR sequencing.}, } @article {pmid28938079, year = {2018}, author = {Rohling, EJ and Marino, G and Foster, GL and Goodwin, PA and von der Heydt, AS and Köhler, P}, title = {Comparing Climate Sensitivity, Past and Present.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {261-288}, doi = {10.1146/annurev-marine-121916-063242}, pmid = {28938079}, issn = {1941-0611}, abstract = {Climate sensitivity represents the global mean temperature change caused by changes in the radiative balance of climate; it is studied for both present/future (actuo) and past (paleo) climate variations, with the former based on instrumental records and/or various types of model simulations. Paleo-estimates are often considered informative for assessments of actuo-climate change caused by anthropogenic greenhouse forcing, but this utility remains debated because of concerns about the impacts of uncertainties, assumptions, and incomplete knowledge about controlling mechanisms in the dynamic climate system, with its multiple interacting feedbacks and their potential dependence on the climate background state. This is exacerbated by the need to assess actuo- and paleoclimate sensitivity over different timescales, with different drivers, and with different (data and/or model) limitations. Here, we visualize these impacts with idealized representations that graphically illustrate the nature of time-dependent actuo- and paleoclimate sensitivity estimates, evaluating the strengths, weaknesses, agreements, and differences of the two approaches. We also highlight priorities for future research to improve the use of paleo-estimates in evaluations of current climate change.}, } @article {pmid28934598, year = {2018}, author = {Gregg, MC and D'Asaro, EA and Riley, JJ and Kunze, E}, title = {Mixing Efficiency in the Ocean.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {443-473}, doi = {10.1146/annurev-marine-121916-063643}, pmid = {28934598}, issn = {1941-0611}, abstract = {Mixing efficiency is the ratio of the net change in potential energy to the energy expended in producing the mixing. Parameterizations of efficiency and of related mixing coefficients are needed to estimate diapycnal diffusivity from measurements of the turbulent dissipation rate. Comparing diffusivities from microstructure profiling with those inferred from the thickening rate of four simultaneous tracer releases has verified, within observational accuracy, 0.2 as the mixing coefficient over a 30-fold range of diapycnal diffusivities. Although some mixing coefficients can be estimated from pycnocline measurements, at present mixing efficiency must be obtained from channel flows, laboratory experiments, and numerical simulations. Reviewing the different approaches demonstrates that estimates and parameterizations for mixing efficiency and coefficients are not converging beyond the at-sea comparisons with tracer releases, leading to recommendations for a community approach to address this important issue.}, } @article {pmid28934597, year = {2018}, author = {Josey, SA and Hirschi, JJ and Sinha, B and Duchez, A and Grist, JP and Marsh, R}, title = {The Recent Atlantic Cold Anomaly: Causes, Consequences, and Related Phenomena.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {475-501}, doi = {10.1146/annurev-marine-121916-063102}, pmid = {28934597}, issn = {1941-0611}, abstract = {Cold ocean temperature anomalies have been observed in the mid- to high-latitude North Atlantic on interannual to centennial timescales. Most notably, a large region of persistently low surface temperatures accompanied by a sharp reduction in ocean heat content was evident in the subpolar gyre from the winter of 2013-2014 to 2016, and the presence of this feature at a time of pervasive warming elsewhere has stimulated considerable debate. Here, we review the role of air-sea interaction and ocean processes in generating this cold anomaly and place it in a longer-term context. We also discuss the potential impacts of surface temperature anomalies for the atmosphere, including the North Atlantic Oscillation and European heat waves; contrast the behavior of the Atlantic with the extreme warm surface event that occurred in the North Pacific over a similar timescale; and consider the possibility that these events represent a response to a change in atmospheric planetary wave forcing.}, } @article {pmid28929570, year = {2018}, author = {Sievers, M and Hale, R and Parris, KM and Swearer, SE}, title = {Impacts of human-induced environmental change in wetlands on aquatic animals.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {529-554}, doi = {10.1111/brv.12358}, pmid = {28929570}, issn = {1469-185X}, abstract = {Many wetlands harbour highly diverse biological communities and provide extensive ecosystem services; however, these important ecological features are being altered, degraded and destroyed around the world. Despite a wealth of research on how animals respond to anthropogenic changes to natural wetlands and how they use created wetlands, we lack a broad synthesis of these data. While some altered wetlands may provide vital habitat, others could pose a considerable risk to wildlife. This risk will be heightened if such wetlands are ecological traps - preferred habitats that confer lower fitness than another available habitat. Wetlands functioning as ecological traps could decrease both local and regional population persistence, and ultimately lead to extinctions. Most studies have examined how animals respond to changes in environmental conditions by measuring responses at the community and population levels, but studying ecological traps requires information on fitness and habitat preferences. Our current lack of knowledge of individual-level responses may therefore limit our capacity to manage wetland ecosystems effectively since ecological traps require different management practices to mitigate potential consequences. We conducted a global meta-analysis to characterise how animals respond to four key drivers of wetland alteration: agriculture, mining, restoration and urbanisation. Our overarching goal was to evaluate the ecological impacts of human alterations to wetland ecosystems, as well as identify current knowledge gaps that limit both the current understanding of these responses and effective wetland management. We extracted 1799 taxon-specific response ratios from 271 studies across 29 countries. Community- (e.g. richness) and population-level (e.g. density) measures within altered wetlands were largely comparable to those within reference wetlands. By contrast, individual fitness measures (e.g. survival) were often lower, highlighting the potential limitations of using only community- and population-level measures to assess habitat quality. Only four studies provided habitat-preference data, preventing investigation of the potential for altered wetlands to function as ecological traps. This is concerning because attempts to identify ecological traps may detect previously unidentified conservation risks. Although there was considerable variability amongst taxa, amphibians were typically the most sensitive taxon, and thus, may be a valuable bio-indicator of wetland quality. Despite suffering reduced survival and reproduction, measures such as time to and mass at metamorphosis were similar between altered and reference wetlands, suggesting that quantifying metamorphosis-related measures in isolation may not provide accurate information on habitat quality. Our review provides the most detailed evaluation to date of the ecological impacts of human alterations to wetland ecosystems. We emphasise that the role of wetlands in human-altered ecosystems can be complex, as they may represent important habitat but also pose potential risks to animals. Reduced availability of natural wetlands is increasing the importance of altered wetlands for aquatic animals. Consequently, we need to define what represents habitat quality from the perspective of animals, and gain a greater understanding of the underlying mechanisms of habitat selection and how these factors could be manipulated. Furthermore, strategies to enhance the quality of these wetlands should be implemented to maximise their conservation potential.}, } @article {pmid28929212, year = {2018}, author = {Parmar, K and Dafale, N and Pal, R and Tikariha, H and Purohit, H}, title = {An Insight into Phage Diversity at Environmental Habitats using Comparative Metagenomics Approach.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {132-141}, pmid = {28929212}, issn = {1432-0991}, mesh = {Bacteriophages/*classification/genetics/*isolation & purification ; *Biodiversity ; *Ecosystem ; Metagenomics ; *Water Microbiology ; }, abstract = {Bacteriophages play significant role in driving microbial diversity; however, little is known about the diversity of phages in different ecosystems. A dynamic predator-prey mechanism called "kill the winner" suggests the elimination of most active bacterial populations through phages. Thus, interaction between phage and host has an effect on the composition of microbial communities in ecosystems. In this study, secondary phage metagenome data from aquatic habitats: wastewater treatment plant (WWTP), fresh, marine, and hot water spring habitat were analyzed using MG-RAST and STAMP tools to explore the diversity of the viruses. Differential relative abundance of phage families-Siphoviridae (34%) and Myoviridae (26%) in WWTP, Myoviridae (30%) and Podoviridae (23%) in fresh water, and Myoviridae (41%) and Podoviridae (8%) in marine-was found to be a discriminating factor among four habitats while Rudiviridae (9%), Globuloviridae (8%), and Lipothrixviridae (1%) were exclusively observed in hot water spring. Subsequently, at genera level, Bpp-1-like virus, Chlorovirus, and T4-like virus were found abundant in WWTP, fresh, and marine habitat, respectively. PCA analysis revealed completely disparate composition of phage in hot water spring from other three ecosystems. Similar analysis of relative abundance of functional features corroborated observations from taxa analysis. Functional features corresponding to phage packaging machinery, replication, integration and excision, and gene transfer discriminated among four habitats. The comparative metagenomics approach exhibited genetically distinct phage communities among four habitats. Results revealed that selective distribution of phage communities would help in understanding the role of phages in food chains, nutrient cycling, and microbial ecology. Study of specific phages would also help in controlling environmental pathogens including MDR bacterial populations using phage therapy approach by selective mining and isolation of phages against specific pathogens persisting in a given environment.}, } @article {pmid28926831, year = {2018}, author = {van Bever, Y and Wolffenbuttel, KP and Brüggenwirth, HT and Blom, E and de Klein, A and Eussen, BHJ and van der Windt, F and Hannema, SE and Dessens, AB and Dorssers, LCJ and Biermann, K and Hersmus, R and de Rijke, YB and Looijenga, LHJ}, title = {Multiparameter Investigation of a 46,XX/46,XY Tetragametic Chimeric Phenotypical Male Patient with Bilateral Scrotal Ovotestes and Ovulatory Activity.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {145-154}, pmid = {28926831}, issn = {1661-5433}, mesh = {46, XX Disorders of Sex Development/blood/genetics/*pathology ; Blood Grouping and Crossmatching ; Disorder of Sex Development, 46,XY/blood/genetics/*pathology ; Female ; Gonads/pathology ; Humans ; Male ; Ovotesticular Disorders of Sex Development/blood/genetics/*pathology ; *Ovulation ; Phenotype ; Polymorphism, Single Nucleotide/genetics ; Young Adult ; }, abstract = {We report on an adult male initially presenting with gynecomastia and a painless scrotal mass without additional genital anomalies. Hyperpigmentation of the skin following the Blaschko's lines was identified. He underwent gonadectomy because of suspected cancer. Histological analyses revealed an ovotestis with ovulatory activity confirmed by immunohistochemistry with multiple markers. Karyotyping of cultured peripheral blood lymphocytes and a buccal smear revealed a 46,XX/46,XY chimeric constitution with different percentages. Multiple molecular analyses as well as blood typing implied a tetragametic origin. After the unilateral gonadectomy, the patient developed recurrent painful cystic swellings of the remaining gonad. Because of the wish to preserve hormonal activity as well as future fertility, the patient underwent surgical resection of a cystic gonadal area. The removed tissue showed ovulation-related features in addition to both testicular and ovarian tissue, diagnosed as an ovotestis. Testosterone therapy was initiated to suppress the persistently elevated gonadotropins and thereby suppress ovarian activity. During treatment, the recurrent pain complaints and cystic swellings ceased, although gonadotropin levels were not fully suppressed. Based on these observations, the importance of a detailed genetic and pathological diagnosis and the clinical dilemmas including the pros and cons of personalized treatment with gonadal preservative surgery are discussed.}, } @article {pmid28925544, year = {2018}, author = {Xie, ZX and Chen, F and Zhang, SF and Wang, MH and Zhang, H and Kong, LF and Dai, MH and Hong, HS and Lin, L and Wang, DZ}, title = {Metaproteomics of marine viral concentrates reveals key viral populations and abundant periplasmic proteins in the oligotrophic deep chlorophyll maximum of the South China Sea.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {477-491}, doi = {10.1111/1462-2920.13937}, pmid = {28925544}, issn = {1462-2920}, abstract = {Viral concentrates (VCs), containing bioinformative DNA and proteins, have been used to study viral diversity, viral metagenomics and virus-host interactions in natural ecosystems. Besides viruses, VCs also contain many noncellular biological components including diverse functional proteins. Here, we used a shotgun proteomic approach to characterize the proteins of VCs collected from the oligotrophic deep chlorophyll maximum (DCM) of the South China Sea. Proteins of viruses infecting picophytoplankton, that is, cyanobacteria and prasinophytes, and heterotrophic bacterioplankton, such as SAR11 and SAR116, dominated the viral proteome. Almost no proteins from RNA viruses or known gene transfer agents were detected, suggesting that they were not abundant at the sampling site. Remarkably, nonviral proteins made up about two thirds of VC proteins, including overwhelmingly abundant periplasmic transporters for nutrient acquisition and proteins for diverse cellular processes, that is, translation, energy metabolism and one carbon metabolism. Interestingly, three 56 kDa selenium-binding proteins putatively involved in peroxide reduction from gammaproteobacteria were abundant in the VCs, suggesting active removal of peroxide compounds at DCM. Our study demonstrated that metaproteomics provides a valuable avenue to explore the diversity and structure of the viral community and also the pivotal biological functions affiliated with microbes in the natural environment.}, } @article {pmid28921784, year = {2018}, author = {Parker, GA and Ramm, SA and Lehtonen, J and Henshaw, JM}, title = {The evolution of gonad expenditure and gonadosomatic index (GSI) in male and female broadcast-spawning invertebrates.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {693-753}, doi = {10.1111/brv.12363}, pmid = {28921784}, issn = {1469-185X}, abstract = {Sedentary broadcast-spawning marine invertebrates, which release both eggs and sperm into the water for fertilization, are of special interest for sexual selection studies. They provide unique insight into the early stages of the evolutionary succession leading to the often-intense operation of both pre- and post-mating sexual selection in mobile gonochorists. Since they are sessile or only weakly mobile, adults can interact only to a limited extent with other adults and with their own fertilized offspring. They are consequently subject mainly to selection on gamete production and gamete success, and so high gonad expenditure is expected in both sexes. We review literature on gonadosomatic index (GSI; the proportion of body tissue devoted to gamete production) of gonochoristic broadcast spawners, which we use as a proxy for gonad expenditure. We show that such taxa most often have a high GSI that is approximately equal in both sexes. When GSI is asymmetric, female GSI usually exceeds male GSI, at least in echinoderms (the majority of species recorded). Intriguingly, though, higher male GSI also occurs in some species and appears more common than female-biased GSI in certain orders of gastropod molluscs. Our limited data also suggest that higher male GSI may be the prevalent pattern in sperm casters (where only males release gametes). We explore how selection might have shaped these patterns using game theoretic models for gonad expenditure that consider possible trade-offs with (i) somatic maintenance or (ii) growth, while also considering sperm competition, sperm limitation, and polyspermy. Our models of the trade-off between somatic tissue (which increases survival) and gonad (which increases reproductive success) predict that GSI should be equal for the two sexes when sperm competition is intense, as is probably common in broadcast spawners due to synchronous spawning in aggregations. Higher female GSI occurs under low sperm competition. Sperm limitation appears unlikely to alter these conclusions qualitatively, but can also act as a force to keep male GSI high, and close to that of females. Polyspermy can act to reduce male GSI. Higher male than female GSI is predicted to be less common (as observed in the data), but can occur when ova/ovaries are sufficiently more resource-intensive to produce than sperm/testes, for which some evidence exists. We also show that sex-specific trade-offs between gonads and growth can generate different life-history strategies for males and females, with males beginning reproduction earlier. This could lead to apparently higher male GSI in empirical studies if immature females are included in calculations of mean GSI. The existence of higher male GSI nonetheless remains somewhat problematic and requires further investigation. When sperm limitation is low, we suggest that the natural logarithm of the male/female GSI ratio may be a suitable index for sperm competition level in broadcast spawners, and that this may also be considered as an index for internally fertilizing taxa.}, } @article {pmid28919506, year = {2018}, author = {Gonçalves, DV and Martínez-Freiría, F and Crochet, PA and Geniez, P and Carranza, S and Brito, JC}, title = {The role of climatic cycles and trans-Saharan migration corridors in species diversification: Biogeography of Psammophis schokari group in North Africa.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {64-74}, doi = {10.1016/j.ympev.2017.09.009}, pmid = {28919506}, issn = {1095-9513}, mesh = {Africa, Northern ; Animal Migration ; Animals ; Bayes Theorem ; Climate ; Cytochromes b/chemistry/genetics ; DNA, Mitochondrial/chemistry/isolation & purification/metabolism ; Genetic Variation ; Likelihood Functions ; NADH Dehydrogenase/chemistry/genetics ; Phylogeny ; Phylogeography ; Sequence Analysis, DNA ; Snakes/*classification/genetics ; }, abstract = {Highlands, hydrographic systems and coastal areas have been hypothesised to form corridors across the hyperarid Sahara desert in North Africa, allowing dispersal and gene flow for non-xeric species. Here we aim to provide a genetic test for the trans-Saharan corridor model, and predict the location and stability of ecological-corridors, by combining phylogeography and palaeoclimatic modelling. The model was the Psammophis schokari (Schokari sand racer) group, fast-moving and widely distributed generalist colubrids occurring mostly in arid and semiarid scrublands. We combined dated phylogenies of mitochondrial and nuclear markers with palaeoclimatic modelling. For the phylogeographic analysis, we used 75 samples of P. schokari and P. aegyptius, and Bayesian and Maximum-Likelihood methods. For the ecological models, we used Maxent over the distribution of P. schokari and West African lineages. Models were projected to past conditions (mid Holocene, Last Glacial Maximum and Last Inter-Glacial) to infer climatic stable areas. Climatic stability was predicted to be mostly restricted to coastal areas and not spatially continuous. A putative temporary trans-Saharan corridor was identified in Eastern Sahara, with a more stable one along the Atlantic coast. Six parapatric lineages were identified within P. schokari, four occurring in North Africa. These likely diverged during the Pliocene. The Tamanraset River might have been a vicariant agent. African lineages may have experienced further subsequent diversification during the late Pleistocene. The main P. schokari refugia were probably located along the northern margins of the Sahara, allowing its North-to-South colonization. Trans-Saharan corridors seem to have played a role in P. schokari biogeography, allowing colonization of central Saharan mountains and Sahel. Some might have worked as refugia, and even the most stable corridors may have sections working as filters, depending on each climatic phase. We expect the use of trans-Saharan corridors to decrease for more mesic species or with less dispersal capabilities.}, } @article {pmid28919505, year = {2018}, author = {Swain, TD}, title = {Revisiting the phylogeny of Zoanthidea (Cnidaria: Anthozoa): Staggered alignment of hypervariable sequences improves species tree inference.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {1-12}, doi = {10.1016/j.ympev.2017.09.008}, pmid = {28919505}, issn = {1095-9513}, mesh = {Animals ; Anthozoa/*classification/genetics ; Base Sequence ; Databases, Genetic ; Phylogeny ; RNA, Ribosomal/chemistry/genetics ; RNA, Ribosomal, 16S/chemistry/genetics ; Sequence Alignment ; }, abstract = {The recent rapid proliferation of novel taxon identification in the Zoanthidea has been accompanied by a parallel propagation of gene trees as a tool of species discovery, but not a corresponding increase in our understanding of phylogeny. This disparity is caused by the trade-off between the capabilities of automated DNA sequence alignment and data content of genes applied to phylogenetic inference in this group. Conserved genes or segments are easily aligned across the order, but produce poorly resolved trees; hypervariable genes or segments contain the evolutionary signal necessary for resolution and robust support, but sequence alignment is daunting. Staggered alignments are a form of phylogeny-informed sequence alignment composed of a mosaic of local and universal regions that allow phylogenetic inference to be applied to all nucleotides from both hypervariable and conserved gene segments. Comparisons between species tree phylogenies inferred from all data (staggered alignment) and hypervariable-excluded data (standard alignment) demonstrate improved confidence and greater topological agreement with other sources of data for the complete-data tree. This novel phylogeny is the most comprehensive to date (in terms of taxa and data) and can serve as an expandable tool for evolutionary hypothesis testing in the Zoanthidea. Spanish language abstract available in Text S1. Translation by L. O. Swain, DePaul University, Chicago, Illinois, 60604, USA.}, } @article {pmid28919504, year = {2018}, author = {Starrett, J and Hayashi, CY and Derkarabetian, S and Hedin, M}, title = {Cryptic elevational zonation in trapdoor spiders (Araneae, Antrodiaetidae, Aliatypus janus complex) from the California southern Sierra Nevada.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {403-413}, doi = {10.1016/j.ympev.2017.09.003}, pmid = {28919504}, issn = {1095-9513}, mesh = {Animals ; California ; Ecological and Environmental Phenomena ; Electron Transport Complex IV/chemistry/classification/genetics ; Genetic Speciation ; Nevada ; Phylogeny ; RNA, Ribosomal, 28S/chemistry/classification/genetics ; Spiders/*classification/genetics ; }, abstract = {The relative roles of ecological niche conservatism versus niche divergence in promoting montane speciation remains an important topic in biogeography. Here, our aim was to test whether lineage diversification in a species complex of trapdoor spiders corresponds with riverine barriers or with an ecological gradient associated with elevational tiering. Aliatypus janus was sampled from throughout its range, with emphasis on populations in the southern Sierra Nevada Mountains of California. We collected multi-locus genetic data to generate a species tree for A. janus and its close relatives. Coalescent based hypothesis tests were conducted to determine if genetic breaks within A. janus conform to riverine barriers. Ecological niche models (ENM) under current and Last Glacial Maximum (LGM) conditions were generated and hypothesis tests of niche conservatism and divergence were performed. Coalescent analyses reveal deeply divergent genetic lineages within A. janus, likely corresponding to cryptic species. Two primary lineages meet along an elevational gradient on the western slopes of the southern Sierra Nevada Mountains. ENMs under both current and LGM conditions indicate that these groups occupy largely non-overlapping niches. ENM hypothesis testing rejected niche identity between the two groups, and supported a sharp ecological gradient occurring where the groups meet. However, the niche similarity test indicated that the two groups may not inhabit different background niches. The Sierra Nevada Mountains provide a natural laboratory for simultaneously testing ecological niche divergence and conservatism and their role in speciation across a diverse range of taxa. Aliatypus janus represents a species complex with cryptic lineages that may have diverged due to parapatric speciation along an ecological gradient, or been maintained by the evolution of ecological niche differences following allopatric speciation.}, } @article {pmid28919503, year = {2018}, author = {Caviedes-Solis, IW and Nieto-Montes de Oca, A}, title = {A multilocus phylogeny of the genus Sarcohyla (Anura: Hylidae), and an investigation of species boundaries using statistical species delimitation.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {184-193}, doi = {10.1016/j.ympev.2017.09.010}, pmid = {28919503}, issn = {1095-9513}, mesh = {Animals ; Anura/*classification/genetics ; Bayes Theorem ; DNA, Mitochondrial/genetics ; *Genetic Loci ; Geography ; Likelihood Functions ; Mexico ; Models, Biological ; *Phylogeny ; Species Specificity ; *Statistics as Topic ; }, abstract = {The genus Sarcohyla is composed by 24 species endemic to México. Despite the large number of phylogenetic studies focusing on the family Hylidae, the relationships among the species of Sarcohyla are still poorly known, and the scarce numbers of specimens and tissue samples available for some of the species has hampered an appropriate phylogenetic analysis. We present the most comprehensive molecular phylogenetic study of Sarcohyla to date. We included 17 species of the genus Sarcohyla using data from two mitochondrial (ND1 and 12S) and three nuclear genes (Rag-1, Rhod, and POMc). We performed phylogenetic analyses using Bayesian inference, and the absence of conflicts with strong support between the separate gene trees indicates that incomplete lineage sorting and/or introgressive hybridization are negligible. A coalescent-based species-tree analysis of the four independent loci (three nuclear genes+mtDNA) mostly supports the same species-level relationships as the analysis of the concatenated data. By including new samples from additional species and localities, we find that: (1) the widely distributed species S. bistincta is a complex of at least three species, (2) another undescribed species exists in the group, (3) the species S. ephemera is not valid and it corresponds to a junior synonym of S. calthula. In addition, we conducted marginal likelihood estimation and used Bayes factors to test alternative species delimitation models for S. bistincta, the most widespread nominal species in the group. Our findings support three independent lineages of S. bistincta group, which are paraphyletic with respect to S. pentheter and S. calthula.}, } @article {pmid28919044, year = {2018}, author = {Dharani, S and Kim, DH and Shanks, RMQ and Doi, Y and Kadouri, DE}, title = {Susceptibility of colistin-resistant pathogens to predatory bacteria.}, journal = {Research in microbiology}, volume = {169}, number = {1}, pages = {52-55}, doi = {10.1016/j.resmic.2017.09.001}, pmid = {28919044}, issn = {1769-7123}, mesh = {Alphaproteobacteria/*physiology ; Anti-Bacterial Agents/*pharmacology ; *Antibiosis ; Bdellovibrio bacteriovorus/*physiology ; Colistin/*pharmacology ; Drug Resistance, Bacterial ; Escherichia coli/*drug effects/genetics/physiology ; Escherichia coli Infections/*microbiology/therapy ; Escherichia coli Proteins/genetics/metabolism ; Humans ; }, abstract = {The increase in multidrug-resistant Gram-negative bacterial infections has forced the reintroduction of antibiotics such as colistin. However, the spread of the plasmid-borne mcr-1 colistin resistance gene have moved us closer to an era of untreatable Gram-negative infections. To evaluate whether predatory bacteria could be used as a potential therapeutic to treat this upcoming threat, the ability of Bdellovibrio bacteriovorus and Micavibrio aeruginosavorus to prey on several clinically relevant mcr-1-positive, colistin-resistant isolates was evaluated. No change in the ability of the predators to prey on free swimming and biofilms of prey cells harboring mcr-1 was measured, as compared to their mcr-1 negative strain.}, } @article {pmid28918535, year = {2018}, author = {Yang, N and Song, F}, title = {Bioprospecting of Novel and Bioactive Compounds from Marine Actinomycetes Isolated from South China Sea Sediments.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {142-149}, pmid = {28918535}, issn = {1432-0991}, support = {ZR2016CB13//Natural Science Foundation of Shandong Province/ ; 31600136//National Natural Science Foundation of China/ ; }, mesh = {Actinobacteria/classification/*genetics/*isolation & purification/metabolism ; Aquatic Organisms/classification/*genetics/*isolation & purification/metabolism ; Biological Factors/*analysis ; *Bioprospecting ; China ; Cluster Analysis ; DNA, Bacterial/chemistry/genetics ; DNA, Ribosomal/chemistry/genetics ; Geologic Sediments/*microbiology ; Phylogeny ; RNA, Ribosomal, 16S/genetics ; Sequence Analysis, DNA ; }, abstract = {Marine actinomycetes are less investigated compared to terrestrial strains as potential sources of natural products. To date, few investigations have been performed on culturable actinomycetes associated with South China Sea sediments. In the present study, twenty-eight actinomycetes were recovered from South China Sea sediments after dereplication by traditional culture-dependent method. The 16S rRNA gene sequences analyses revealed that these strains related to five families and seven genera. Twelve representative strains possessed at least one of the biosynthetic genes coding for polyketide synthase I, II, and nonribosomal peptide synthetase. Four strains had anti-Mycobacterium phlei activities and five strains had activities against methicillin-resistant Staphylococcus aureus. 10 L-scale fermentation of strains Salinispora sp. NHF45, Nocardiopsis sp. NHF48, and Streptomyces sp. NHF86 were carried out for novel and bioactive compounds discovery. Finally, we obtained a novel α-pyrone compound from marine Nocardiopsis sp. NHF48, an analogue of paulomenol from marine Streptomyces sp. NHF86 and a new source of rifamycin B, produced by Salinispora sp. NHF45. The present study concluded that marine actinomycetes, which we isolated from South China Sea sediments, will be a suitable source for the development of novel and bioactive compounds.}, } @article {pmid28913952, year = {2018}, author = {Brandeis, M}, title = {New-age ideas about age-old sex: separating meiosis from mating could solve a century-old conundrum.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {2}, pages = {801-810}, doi = {10.1111/brv.12367}, pmid = {28913952}, issn = {1469-185X}, abstract = {Ever since Darwin first addressed it, sexual reproduction reigns as the 'queen' of evolutionary questions. Multiple theories tried to explain how this apparently costly and cumbersome method has become the universal mode of eukaryote reproduction. Most theories stress the adaptive advantages of sex by generating variation, they fail however to explain the ubiquitous persistence of sexual reproduction also where adaptation is not an issue. I argue that the obstacle for comprehending the role of sex stems from the conceptual entanglement of two distinct processes - gamete production by meiosis and gamete fusion by mating (mixis). Meiosis is an ancient, highly rigid and evolutionary conserved process identical and ubiquitous in all eukaryotes. Mating, by contrast, shows tremendous evolutionary variability even in closely related clades and exhibits wonderful ecological adaptability. To appreciate the respective roles of these two processes, which are normally linked and alternating, we require cases where one takes place without the other. Such cases are rather common. The heteromorphic sex chromosomes Y and W, that do not undergo meiotic recombination are an evolutionary test case for demonstrating the role of meiosis. Substantial recent genomic evidence highlights the accelerated rates of change and attrition these chromosomes undergo in comparison to those of recombining autosomes. I thus propose that the most basic role of meiosis is conserving integrity of the genome. A reciprocal case of meiosis without bi-parental mating, is presented by self-fertilization, which is fairly common in flowering plants, as well as most types of apomixis. I argue that deconstructing sex into these two distinct processes - meiosis and mating - will greatly facilitate their analysis and promote our understanding of sexual reproduction.}, } @article {pmid28911979, year = {2018}, author = {Veatch, AV and Kaushal, D}, title = {Opening Pandora's Box: Mechanisms of Mycobacterium tuberculosis Resuscitation.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {145-157}, pmid = {28911979}, issn = {1878-4380}, support = {R01 AI089323/AI/NIAID NIH HHS/United States ; R01 AI111943/AI/NIAID NIH HHS/United States ; R01 AI134240/AI/NIAID NIH HHS/United States ; R01 HL106790/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Antitubercular Agents/therapeutic use ; Bacterial Proteins/immunology/metabolism ; Humans ; Latent Tuberculosis ; Models, Animal ; Mycobacterium tuberculosis/*pathogenicity ; Tuberculosis/*immunology/prevention & control/therapy ; }, abstract = {Mycobacterium tuberculosis (Mtb) characteristically causes an asymptomatic infection. While this latent tuberculosis infection (LTBI) is not contagious, reactivation to active tuberculosis disease (TB) causes the patient to become infectious. A vaccine has existed for TB for a century, while drug treatments have been available for over 70 years; despite this, TB remains a major global health crisis. Understanding the factors which allow the bacillus to control responses to host stress and mechanisms leading to latency are critical for persistence. Similarly, molecular switches which respond to reactivation are important. Recently, research in the field has sought to focus on reactivation, employing system-wide approaches and animal models. Here, we describe the current work that has been done to elucidate the mechanisms of reactivation and stop reactivation in its tracks.}, } @article {pmid28905106, year = {2018}, author = {Namai, F and Shigemori, S and Sudo, K and Sato, T and Yamamoto, Y and Nigar, S and Ogita, T and Shimosato, T}, title = {Recombinant Mouse Osteocalcin Secreted by Lactococcus lactis Promotes Glucagon-Like Peptide-1 Induction in STC-1 Cells.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {92-98}, pmid = {28905106}, issn = {1432-0991}, mesh = {Animals ; Biological Transport ; Enteroendocrine Cells/drug effects/*metabolism ; Gene Expression ; Glucagon-Like Peptide 1/genetics/*metabolism ; Lactococcus lactis/*genetics/metabolism ; Mice ; Nisin/metabolism ; Osteocalcin/genetics/*metabolism/pharmacology ; }, abstract = {An osteoblastic protein, osteocalcin (OC), exists in vivo in two forms: carboxylated OC, and uncarboxylated or low-carboxylated OC (ucOC). ucOC acts as a hormone to regulate carbon and energy metabolism. Recent studies demonstrated that ucOC exerts insulinotropic effects, mainly through the glucagon-like peptide 1 (GLP-1) pathway. GLP-1 is an insulinotropic hormone secreted by enteroendocrine L cells in the small intestine. Thus, efficient delivery of ucOC to the small intestine may be a new therapeutic option for metabolic diseases such as diabetes and obesity. Here, we genetically engineered a lactic acid bacterium, Lactococcus lactis, to produce recombinant mouse ucOC. Western blotting showed that the engineered strain (designated NZ-OC) produces and secretes the designed peptide (rOC) in the presence of nisin, an inducer of the recombinant gene. Highly-purified rOC was obtained from the culture supernatants of NZ-OC using immobilized metal affinity chromatography. An in vitro assay showed that purified rOC promotes GLP-1 secretion in a mouse intestinal neuroendocrine cell line, STC-1, in a dose-dependent manner. These results clearly demonstrate that NZ-OC secretes rOC, and that rOC can promote GLP-1 secretion by STC-1 cells. Genetically modified lactic acid bacteria (gmLAB) have been proposed over the last two decades as an effective and low-cost mucosal delivery vehicle for biomedical proteins. NZ-OC may be an attractive tool for the delivery of rOC to trigger GLP-1 secretion in the small intestine to treat diabetes and obesity.}, } @article {pmid28901723, year = {2018}, author = {de Castro, ÉCP and Zagrobelny, M and Cardoso, MZ and Bak, S}, title = {The arms race between heliconiine butterflies and Passiflora plants - new insights on an ancient subject.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {555-573}, doi = {10.1111/brv.12357}, pmid = {28901723}, issn = {1469-185X}, abstract = {Heliconiines are called passion vine butterflies because they feed exclusively on Passiflora plants during the larval stage. Many features of Passiflora and heliconiines indicate that they have radiated and speciated in association with each other, and therefore this model system was one of the first examples used to exemplify coevolution theory. Three major adaptations of Passiflora plants supported arguments in favour of their coevolution with heliconiines: unusual variation of leaf shape within the genus; the occurrence of yellow structures mimicking heliconiine eggs; and their extensive diversity of defence compounds called cyanogenic glucosides. However, the protection systems of Passiflora plants go beyond these three features. Trichomes, mimicry of pathogen infection through variegation, and production of extrafloral nectar to attract ants and other predators of their herbivores, are morphological defences reported in this plant genus. Moreover, Passiflora plants are well protected chemically, not only by cyanogenic glucosides, but also by other compounds such as alkaloids, flavonoids, saponins, tannins and phenolics. Heliconiines can synthesize cyanogenic glucosides themselves, and their ability to handle these compounds was probably one of the most crucial adaptations that allowed the ancestor of these butterflies to feed on Passiflora plants. Indeed, it has been shown that Heliconius larvae can sequester cyanogenic glucosides and alkaloids from their host plants and utilize them for their own benefit. Recently, it was discovered that Heliconius adults have highly accurate visual and chemosensory systems, and the expansion of brain structures that can process such information allows them to memorize shapes and display elaborate pre-oviposition behaviour in order to defeat visual barriers evolved by Passiflora species. Even though the heliconiine-Passiflora model system has been intensively studied, the forces driving host-plant preference in these butterflies remain unclear. New studies have shown that host-plant preference seems to be genetically controlled, but in many species there is some plasticity in this choice and preferences can even be induced. Although much knowledge regarding the coevolution of Passiflora plants and heliconiine butterflies has accumulated in recent decades, there remain many exciting unanswered questions concerning this model system.}, } @article {pmid28900701, year = {2018}, author = {Zhu, W and Wei, W and Zhang, S and Zheng, Y and Chen, P and Xu, X}, title = {The Phosphatome of Medicinal and Edible Fungus Wolfiporia cocos.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {124-131}, pmid = {28900701}, issn = {1432-0991}, support = {2017y12//Scientific Research Foundation Granted From Wuhan Polytechnic University/ ; }, mesh = {Gene Expression Profiling ; Mycelium/growth & development ; Phosphoprotein Phosphatases/analysis/*genetics ; Real-Time Polymerase Chain Reaction ; Secondary Metabolism ; Sequence Homology ; Stress, Physiological ; Wolfiporia/*genetics/growth & development/metabolism ; }, abstract = {Wolfiporia cocos is an important medicinal and edible fungus that grows in association with pine trees, and its dried sclerotium has been used as a traditional medicine in China for centuries. However, the commercial production of W. cocos sclerotia is currently limited by shortages in pine wood resources. Since protein phosphatases (PPs) play significant roles in growth, signal transduction, development, metabolism, sexual reproduction, cell cycle, and environmental stress responses in fungi, the phosphatome of W. cocos was analyzed in this study by identifying PP genes, studying transcript profiles and assigning PPs to orthologous groups. Fifty-four putative PP genes were putatively identified in W. cocos genome based on homologous sequences searching using BLASTx program against the Saccharomyces cerevisiae, Fusarium graminearum, and Sclerotinia sclerotiorum databases. Based on known and presumed functions of orthologues of these PP genes found in other fungi, the putative roles of these W. cocos PPs in colonization, hyphal growth, sclerotial formation, secondary metabolism, and stress tolerance to environment were discussed in this study. And the level of transcripts from PP genes in the mycelium and sclerotium stages was also analyzed by qRT-PCR. Our study firstly identified and functional discussed the phosphatome in the medicinal and edible fungus W. cocos. The data from our study contribute to a better understanding of PPs potential roles in various cellar processes of W. cocos, and systematically provide comprehensive and novel insights into W. cocos economically important traits that could be extended to other fungi.}, } @article {pmid28900693, year = {2018}, author = {Daas, MJA and Vriesendorp, B and van de Weijer, AHP and van der Oost, J and van Kranenburg, R}, title = {Complete Genome Sequence of Geobacillus thermodenitrificans T12, A Potential Host for Biotechnological Applications.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {49-56}, pmid = {28900693}, issn = {1432-0991}, mesh = {Base Composition ; Biotechnology ; *Genome, Bacterial ; Geobacillus/*genetics/metabolism ; Plasmids/genetics/metabolism ; Polysaccharides/metabolism ; Xylose/metabolism ; }, abstract = {In attempt to obtain a thermophilic host for the conversion of lignocellulose derived substrates into lactic acid, Geobacillus thermodenitrificans T12 was isolated from a compost heap. It was selected from over 500 isolates as a genetically tractable hemicellulolytic lactic acid producer, requiring little nutrients. The strain is able to ferment glucose and xylose simultaneously and can produce lactic acid from xylan, making it a potential host for biotechnological applications. The genome of strain T12 consists of a 3.64 Mb chromosome and two plasmids of 59 and 56 kb. It has a total of 3.676 genes with an average genomic GC content of 48.7%. The T12 genome encodes a denitrification pathway, allowing for anaerobic respiration. The identity and localization of the responsible genes are similar to those of the denitrification pathways found in strain NG80-2. The hemicellulose utilization (HUS) locus was identified based on sequence homology against G. stearothermophilus T-6. It appeared that T12 has all the genes that are present in strain T-6 except for the arabinan degradation cluster. Instead, the HUS locus of strain T12 contains genes for both an inositol and a pectate degradation pathway. Strain T12 has complete pathways for the synthesis of purine and pyrimidine, all 20 amino acids and several vitamins except D-biotin. The host-defense systems present comprise a Type II and a Type III restriction-modification system, as well as a CRISPR-Cas Type II system. It is concluded that G. thermodenitrificans T12 is a potentially interesting candidate for industrial applications.}, } @article {pmid28900692, year = {2018}, author = {Babykin, MM and Obando, TSA and Zinchenko, VV}, title = {TonB-Dependent Utilization of Dihydroxamate Xenosiderophores in Synechocystis sp. PCC 6803.}, journal = {Current microbiology}, volume = {75}, number = {2}, pages = {117-123}, pmid = {28900692}, issn = {1432-0991}, support = {13-04-01767//Russian Foundation for Basic Research/ ; }, mesh = {Bacterial Proteins/genetics/*metabolism ; Gene Knockout Techniques ; Hydroxamic Acids/*metabolism ; Iron/*metabolism ; Membrane Proteins/genetics/*metabolism ; Siderophores/*metabolism ; Synechocystis/genetics/*metabolism ; }, abstract = {In Gram-negative bacteria, transport of ferric siderophores through outer membrane is a complex process that requires specific outer membrane transporters and energy-transducing TonB-ExbB-ExbD system in the cytoplasmic membrane. The genome of the non-siderophore-producing cyanobacterium Synechocystis sp. PCC 6803 encodes all putative components of the siderophore-mediated iron uptake system. So far, there has been no experimental evidence for the existence of such a pathway in this organism. On the contrary, its reductive iron uptake pathway has been studied in detail. We demonstrate that Synechocystis sp. PCC 6803 is capable of using dihydroxamate xenosiderophores, either ferric schizokinen (FeSK) or a siderophore of the filamentous cyanobacterium Anabaena variabilis ATCC 29413 (SAV), as the sole source of iron. Inactivation of the tonB gene or the exbB1-exbD1 gene cluster resulted in an inability to utilize these siderophores. At the same time, the inactivation of the feoB gene encoding FeoB plasma membrane ferrous iron transporter, or one of the futB or futC genes encoding permease and ATPase subunit of FutABC ferric iron transporter, did not impair the ability of cells to utilize FeSK or SAV as the sole source of iron for growth. Our data suggest that cyanobacterium Synechocystis sp. PCC 6803 is capable of acquiring iron-siderophore complexes in a TonB-dependent manner without iron reduction in the periplasm.}, } @article {pmid28898878, year = {2018}, author = {Audí, L and Camats, N and Fernández-Cancio, M and Granada, ML}, title = {Development of Laboratory Investigations in Disorders of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {7-18}, doi = {10.1159/000479719}, pmid = {28898878}, issn = {1661-5433}, mesh = {Animals ; Clinical Laboratory Techniques/*methods ; Cytogenetic Analysis ; Disease Models, Animal ; Disorders of Sex Development/*diagnosis/genetics ; Genetic Association Studies ; Hormones/analysis/isolation & purification ; Humans ; }, abstract = {Scientific knowledge to understand the biological basis of sex development was prompted by the observation of variants different from the 2 most frequent body types, and this became one of the fields first studied by modern pediatric endocrinology. The clinical observation was supported by professionals working in different areas of laboratory sciences which led to the description of adrenal and gonadal steroidogenesis, the enzymes involved, and the different deficiencies. Steroid hormone measurements evolved from colorimetry to radioimmunoassay (RIA) and automated immunoassays, although gas and liquid chromatography coupled to mass spectrometry are now the gold standard techniques for steroid measurements. Peptide hormones and growth factors were purified, and their measurement evolved from RIA to automated immunoassays. Hormone action mechanisms were described, and their specific receptors were characterized and assayed in experimental materials and in patient tissues and cell cultures. The discovery of the genetic basis for variant sex developments began with the description of the sex chromosomes. Molecular technology allowed cloning of genes coding for the different proteins involved in sex determination and development. Experimental animal models aided in verifying the roles of proteins and also suggested new genes to be investigated. New candidate genes continue to be described based on experimental models and on next-generation sequencing of patient DNAs.}, } @article {pmid28893860, year = {2018}, author = {Top, D and Young, MW}, title = {Coordination between Differentially Regulated Circadian Clocks Generates Rhythmic Behavior.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a033589}, pmid = {28893860}, issn = {1943-0264}, support = {R37 GM054339/GM/NIGMS NIH HHS/United States ; }, abstract = {Specialized groups of neurons in the brain are key mediators of circadian rhythms, receiving daily environmental cues and communicating those signals to other tissues in the organism for entrainment and to organize circadian physiology. In Drosophila, the "circadian clock" is housed in seven neuronal clusters, which are defined by their expression of the main circadian proteins, Period, Timeless, Clock, and Cycle. These clusters are distributed across the fly brain and are thereby subject to the respective environments associated with their anatomical locations. While these core components are universally expressed in all neurons of the circadian network, additional regulatory proteins that act on these components are differentially expressed, giving rise to "local clocks" within the network that nonetheless converge to regulate coherent behavioral rhythms. In this review, we describe the communication between the neurons of the circadian network and the molecular differences within neurons of this network. We focus on differences in protein-expression patterns and discuss how such variation can impart functional differences in each local clock. Finally, we summarize our current understanding of how communication within the circadian network intersects with intracellular biochemical mechanisms to ultimately specify behavioral rhythms. We propose that additional efforts are required to identify regulatory mechanisms within each neuronal cluster to understand the molecular basis of circadian behavior.}, } @article {pmid28893859, year = {2018}, author = {Rübsam, M and Broussard, JA and Wickström, SA and Nekrasova, O and Green, KJ and Niessen, CM}, title = {Adherens Junctions and Desmosomes Coordinate Mechanics and Signaling to Orchestrate Tissue Morphogenesis and Function: An Evolutionary Perspective.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a029207}, pmid = {28893859}, issn = {1943-0264}, support = {P30 AR057216/AR/NIAMS NIH HHS/United States ; R01 AR043380/AR/NIAMS NIH HHS/United States ; T32 AR007593/AR/NIAMS NIH HHS/United States ; R01 CA122151/CA/NCI NIH HHS/United States ; R01 AR041836/AR/NIAMS NIH HHS/United States ; }, abstract = {Cadherin-based adherens junctions (AJs) and desmosomes are crucial to couple intercellular adhesion to the actin or intermediate filament cytoskeletons, respectively. As such, these intercellular junctions are essential to provide not only integrity to epithelia and other tissues but also the mechanical machinery necessary to execute complex morphogenetic and homeostatic intercellular rearrangements. Moreover, these spatially defined junctions serve as signaling hubs that integrate mechanical and chemical pathways to coordinate tissue architecture with behavior. This review takes an evolutionary perspective on how the emergence of these two essential intercellular junctions at key points during the evolution of multicellular animals afforded metazoans with new opportunities to integrate adhesion, cytoskeletal dynamics, and signaling. We discuss known literature on cross-talk between the two junctions and, using the skin epidermis as an example, provide a model for how these two junctions function in concert to orchestrate tissue organization and function.}, } @article {pmid28893858, year = {2018}, author = {Braga, V}, title = {Signaling by Small GTPases at Cell-Cell Junctions: Protein Interactions Building Control and Networks.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a028746}, pmid = {28893858}, issn = {1943-0264}, abstract = {A number of interesting reports highlight the intricate network of signaling proteins that coordinate formation and maintenance of cell-cell contacts. We have much yet to learn about how the in vitro binding data is translated into protein association inside the cells and whether such interaction modulates the signaling properties of the protein. What emerges from recent studies is the importance to carefully consider small GTPase activation in the context of where its activation occurs, which upstream regulators are involved in the activation/inactivation cycle and the GTPase interacting partners that determine the intracellular niche and extent of signaling. Data discussed here unravel unparalleled cooperation and coordination of functions among GTPases and their regulators in supporting strong adhesion between cells.}, } @article {pmid28893659, year = {2018}, author = {Sarkar, A and Ghosh, PK and Pramanik, K and Mitra, S and Soren, T and Pandey, S and Mondal, MH and Maiti, TK}, title = {A halotolerant Enterobacter sp. displaying ACC deaminase activity promotes rice seedling growth under salt stress.}, journal = {Research in microbiology}, volume = {169}, number = {1}, pages = {20-32}, doi = {10.1016/j.resmic.2017.08.005}, pmid = {28893659}, issn = {1769-7123}, mesh = {Bacterial Proteins/genetics/*metabolism ; Carbon-Carbon Lyases/genetics/*metabolism ; Enterobacter/classification/*enzymology/genetics/isolation & purification ; Oryza/*growth & development/*microbiology ; Phylogeny ; Seedlings/*growth & development/microbiology ; Sodium Chloride/analysis/*metabolism ; }, abstract = {Agricultural productivity is proven to be hampered by the synthesis of reactive oxygen species (ROS) and production of stress-induced ethylene under salinity stress. One-aminocyclopropane-1-carboxylic acid (ACC) is the direct precursor of ethylene synthesized by plants. Bacteria possessing ACC deaminase activity can use ACC as a nitrogen source preventing ethylene production. Several salt-tolerant bacterial strains displaying ACC deaminase activity were isolated from rice fields, and their plant growth-promoting (PGP) properties were determined. Among them, strain P23, identified as an Enterobacter sp. based on phenotypic characteristics, matrix-assisted laser desorption ionization-time of flight mass spectrometry data and the 16S rDNA sequence, was selected as the best-performing isolate for several PGP traits, including phosphate solubilization, IAA production, siderophore production, HCN production, etc. Enterobacter sp. P23 was shown to promote rice seedling growth under salt stress, and this effect was correlated with a decrease in antioxidant enzymes and stress-induced ethylene. Isolation of an acdS mutant strain enabled concluding that the reduction in stress-induced ethylene content after inoculation of strain P23 was linked to ACC deaminase activity.}, } @article {pmid28892253, year = {2018}, author = {Parker, A and Lawson, MAE and Vaux, L and Pin, C}, title = {Host-microbe interaction in the gastrointestinal tract.}, journal = {Environmental microbiology}, volume = {20}, number = {7}, pages = {2337-2353}, pmid = {28892253}, issn = {1462-2920}, abstract = {The gastrointestinal tract is a highly complex organ in which multiple dynamic physiological processes are tightly coordinated while interacting with a dense and extremely diverse microbial population. From establishment in early life, through to host-microbe symbiosis in adulthood, the gut microbiota plays a vital role in our development and health. The effect of the microbiota on gut development and physiology is highlighted by anatomical and functional changes in germ-free mice, affecting the gut epithelium, immune system and enteric nervous system. Microbial colonisation promotes competent innate and acquired mucosal immune systems, epithelial renewal, barrier integrity, and mucosal vascularisation and innervation. Interacting or shared signalling pathways across different physiological systems of the gut could explain how all these changes are coordinated during postnatal colonisation, or after the introduction of microbiota into germ-free models. The application of cell-based in-vitro experimental systems and mathematical modelling can shed light on the molecular and signalling pathways which regulate the development and maintenance of homeostasis in the gut and beyond.}, } @article {pmid28888938, year = {2018}, author = {Kaboré, S and Cecchi, P and Mosser, T and Toubiana, M and Traoré, O and Ouattara, AS and Traoré, AS and Barro, N and Colwell, RR and Monfort, P}, title = {Occurrence of Vibrio cholerae in water reservoirs of Burkina Faso.}, journal = {Research in microbiology}, volume = {169}, number = {1}, pages = {1-10}, doi = {10.1016/j.resmic.2017.08.004}, pmid = {28888938}, issn = {1769-7123}, mesh = {Bacterial Proteins/genetics/metabolism ; Burkina Faso ; Cholera/microbiology ; Fresh Water/*microbiology ; Humans ; Vibrio cholerae/classification/genetics/*isolation & purification/metabolism ; Water Pollution ; Water Resources ; }, abstract = {Africa is currently an important region in which cholera epidemics occur. Little is known about the presence of Vibrio cholerae in freshwater bodies in Africa. There are ca. 1700 lakes and reservoirs in Burkina Faso, most of which have been built within recent decades to secure water resources. The purpose of this study was to investigate the presence of V. cholerae in the water of reservoirs, using the most-probable-number polymerase chain reaction. Results showed that V. cholerae could be detected in water samples collected from 14 of 39 sampled reservoirs. The concentrations varied from 0 MPN/l to more than 1100 MPN/l. Fifty strains of V. cholerae isolated on CHROMagar™ vibrio were identified as V. cholerae non-O1/non-O139, none of which carried the ctxA gene. A significant positive correlation was found between the presence of V. cholerae in the reservoirs and both alkaline pH and phytoplankton biomass. V. cholerae was present in significantly higher numbers in reservoirs of urban areas than in rural areas. Since V. cholerae non-O1/non-O139 has been shown to be a causative agent of endemic diarrheal outbreaks, their presence in Burkina Faso reservoirs suggests they may play a role in gastroenteritis in that country.}, } @article {pmid28888791, year = {2018}, author = {Furfaro, G and Salvi, D and Mancini, E and Mariottini, P}, title = {A multilocus view on Mediterranean aeolid nudibranchs (Mollusca): Systematics and cryptic diversity of Flabellinidae and Piseinotecidae.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {13-22}, doi = {10.1016/j.ympev.2017.09.001}, pmid = {28888791}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; Biodiversity ; Gastropoda/anatomy & histology/*classification/genetics ; Likelihood Functions ; Mediterranean Sea ; Phylogeny ; RNA, Ribosomal, 16S/chemistry/genetics ; }, abstract = {Recent molecular studies revealed high level of endemism and numerous cryptic species within opisthobranchs, with Mediterranean taxa clearly understudied. Here we used genetic data from both mitochondrial and nuclear gene fragments as well as morphological data from taxonomically relevant characters to investigate the phylogenetic relationships and systematics of Mediterranean taxa of the Flabellinidae and Piseinotecidae families. Phylogenetic analyses based on Bayesian and Maximum-Likelihood methods indicate that Flabellinidae and Pisenotecidae taxa and species within the genera Flabellina, Calmella and Piseinotecus do not form monophyletic clades. These results are supported by our morphological analyses which allowed the re-evaluation of the triseriate radula condition in Pisenotecidae and Calmella taxa and their inclusion in the genus Flabellina as Flabellina gaditanacomb. nov. (synonym of F. confusa), Flabellina gabiniereicomb. nov. and Flabellina cavolinicomb. nov. Species delimitation and barcoding gap analyses allowed uncovering cryptic species within Flabellina gracilis (Alder and Hancock, 1844), F. trophina (Bergh, 1890), F. verrucosa (M. Sars, 1829) and F. ischitana Hirano and Thompson, 1990, the latter with an Atlantic form which is under description. This study corroborates the relevance of combining molecular and morphological data from multiple populations and species in the assessment of nudibranch diversity and classification.}, } @article {pmid28888790, year = {2018}, author = {Simpson, L and Clements, MA and Crayn, DM and Nargar, K}, title = {Evolution in Australia's mesic biome under past and future climates: Insights from a phylogenetic study of the Australian Rock Orchids (Dendrobium speciosum complex, Orchidaceae).}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {32-46}, doi = {10.1016/j.ympev.2017.09.004}, pmid = {28888790}, issn = {1095-9513}, mesh = {Amplified Fragment Length Polymorphism Analysis ; Australia ; Biological Evolution ; Climate Change ; DNA, Plant/chemistry/metabolism ; Dendrobium/*classification/genetics ; Ecosystem ; Genetic Variation ; Phylogeny ; }, abstract = {The Australian mesic biome spans c. 33° of latitude along Australia's east coast and ranges and is dissected by historical and contemporary biogeographical barriers. To investigate the impact of these barriers on evolutionary diversification and to predict the impact of future climate change on the distribution of species and genetic diversity within this biome, we inferred phylogenetic relationships within the Dendrobium speciosum complex (Orchidaceae) across its distribution and undertook environmental niche modelling (ENM) under past, contemporary and projected future climates. Neighbor Joining tree inference, NeighborNet and Structure analyses of Amplified Fragment Length Polymorphism (AFLP) profiles for D. speciosum sampled from across its distribution showed that the complex consists of two highly supported main groups that are geographically separated by the St. Lawrence gap, an area of dry sclerophyll forest and woodland. The presence of several highly admixed individuals identified by the Structure analysis provided evidence of genetic exchange between the two groups across this gap. Whereas previous treatments have recognised between one to eleven species, the molecular results support the taxonomic treatment of the complex as a single species with two subspecies. The ENM analysis supported the hypothesis that lineage divergence within the complex was driven by past climatic changes. The St. Lawrence gap represented a stronger biogeographic barrier for the D. speciosum complex during the cool and dry glacial climatic conditions of the Pleistocene than under today's interglacial conditions. Shallow genetic divergence was found within the two lineages, which mainly corresponded to three other biogeographic barriers: the Black Mountain Corridor, Glass House Mountains and the Hunter Valley. Our ENM analyses provide further support for the hypothesis that biogeographic barriers along Australia's east coast were somewhat permeable to genetic exchange due to past episodic range expansions and contractions caused by climatic change resulting in recurrent contact between previously isolated populations. An overall southward shift in the distribution of the complex under future climate scenarios was predicted, with the strongest effects on the northern lineage. This study contributes to our understanding of the factors shaping biodiversity patterns in Australia's mesic biome.}, } @article {pmid28887647, year = {2018}, author = {Hsieh, YH and Simpson, S and Kerdahi, K and Sulaiman, IM}, title = {A Comparative Evaluation Study of Growth Conditions for Culturing the Isolates of Campylobacter spp.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {71-78}, pmid = {28887647}, issn = {1432-0991}, support = {FDA Commissioner's Fellowship Program//FDA Commissioner's Fellowship Program/ ; }, mesh = {Animals ; Campylobacter/classification/genetics/*growth & development/isolation & purification ; Campylobacter Infections/*microbiology ; Cattle ; Culture Media/*chemistry/metabolism ; Eggs/microbiology ; Food Contamination/analysis ; Humans ; Milk/microbiology ; }, abstract = {Campylobacter is one of the leading causes of foodborne travelers' diarrhea worldwide. Although a large number cases of campylobacteriosis go undiagnosed or unreported, it is considered as the second most common foodborne illness in the USA affecting over 1.3 million individuals every year. Of various Campylobacter species, C. jejuni, C. coli, and C. lari have been accounted for causing more than 99% of human infections. Thus, there is a need to have efficient isolation method to protect public health on food safety and monitoring the burden of campylobacteriosis. Nevertheless, it is a challenging task as the exposure of environmental stress during isolation process makes Campylobacter species less culturable. Sixteen Campylobacter spp. were used to evaluate the current protocols used in Campylobacter isolation. For optimal recovery, a range of growth media (Bolton, Columbia, Muller Hinton, CVA Campy and mCCDA), incubation temperatures, and additional supplements (including antibiotics) were tested. Blood agars without antibiotics were sufficient for the initial recovery. Afterward, the isolates could grow on agars without any supplements, and in some cases growth was observed in the presence of antibiotics. Incubation at 37 °C was found to be the optimal temperature for the recovery and the growth of most species. Additionally, a food adulteration study was also carried out by artificially contaminating three food matrices that included egg, milk, and infant cereal, with two isolates of C. jejuni and C. coli. Results of this study should provide the insight for culturing and isolation of Campylobacter from food and other sources.}, } @article {pmid28884372, year = {2018}, author = {Jani, K and Ghattargi, V and Pawar, S and Inamdar, M and Shouche, Y and Sharma, A}, title = {Anthropogenic Activities Induce Depletion in Microbial Communities at Urban Sites of the River Ganges.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {79-83}, pmid = {28884372}, issn = {1432-0991}, support = {BT/PR/0054/NDB/52/94/2007//Department of Biotechnology , Ministry of Science and Technology/ ; }, mesh = {Bacteria/classification/genetics/*isolation & purification ; Biodiversity ; Ecosystem ; India ; Phylogeny ; Rivers/chemistry/*microbiology ; }, abstract = {The Ganges is the largest river of India, worshiped by Hindus with a belief that bathing in the river causes the remission of sins and is considered very pure. It is heavily polluted by the unrestricted human usage including ritual practices, urbanization, and industrialization. Such perturbations may subsequently influence the bacterial community composition and ecosystem functioning. Here, we applied targeted amplicon sequencing to determine the impact of spatial variation on the microbial community assemblage of the Ganga River. The river bacterial community demonstrates taxonomic variability across the sites with accumulation of Firmicutes (20.9%) Verrucomicrobia (6.09%), Actinobacteria (4.51%), and Synergistetes (1.16%), at rural site while Proteobacteria (49.4%) and Bacteroidetes (12.7%) predominate at urban sites. Furthermore, sites under study establish the unique taxonomic signature which could represent the impact of spatial variation on the microbial community assemblage.}, } @article {pmid28881466, year = {2018}, author = {Beale, PK and Marsh, KJ and Foley, WJ and Moore, BD}, title = {A hot lunch for herbivores: physiological effects of elevated temperatures on mammalian feeding ecology.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {674-692}, doi = {10.1111/brv.12364}, pmid = {28881466}, issn = {1469-185X}, abstract = {Mammals maintain specific body temperatures (Tb) across a broad range of ambient temperatures. The energy required for thermoregulation ultimately comes from the diet, and so what animals eat is inextricably linked to thermoregulation. Endothermic herbivores must balance energy requirements and expenditure with complicated thermoregulatory challenges from changing thermal, nutritional and toxicological environments. In this review we provide evidence that plant-based diets can influence thermoregulation beyond the control of herbivores, and that this can render them susceptible to heat stress. Notably, herbivorous diets often require specialised digestive systems, are imbalanced, and contain plant secondary metabolites (PSMs). PSMs in particular are able to interfere with the physiological processes responsible for thermoregulation, for example by uncoupling mitochondrial oxidative phosphorylation, binding to thermoreceptors, or because the pathways required to detoxify PSMs are thermogenic. It is likely, therefore, that increased ambient temperatures due to climate change may have greater and more-specific impacts on herbivores than on other mammals, and that managing internal and external heat loads under these conditions could drive changes in feeding ecology.}, } @article {pmid28881067, year = {2018}, author = {Zhang, W and Pan, Y and Yang, J and Chen, H and Holohan, B and Vaudrey, J and Lin, S and McManus, GB}, title = {The diversity and biogeography of abundant and rare intertidal marine microeukaryotes explained by environment and dispersal limitation.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {462-476}, doi = {10.1111/1462-2920.13916}, pmid = {28881067}, issn = {1462-2920}, abstract = {Benthic microeukaryotes are key ecosystem drivers in marine sandy beaches, an important and dynamic environment; however, little is known about their diversity and biogeography on a large spatial scale. Here, we investigated the community composition and geographical distributions of benthic microeukaryotes using high-throughput sequencing of the 18S rRNA gene and quantified the contributions of environmental factors and spatial separation on the distribution patterns of both rare and abundant taxa. We collected 36 intertidal samples at 12 sandy beaches from four regions that spanned distances from 0.001 to 12,000 km. We found 12,890 operational taxonomic units (OTUs; 97% sequence identity level) including members of all eukaryotic super-groups and several phyla of uncertain position. Arthropoda and Diatomeae dominated the sequence reads in abundance, but Ciliophora and Discoba were the most diverse groups across all samples. About one-third of the OTUs could not be definitively classified at a similarity level of 80%, supporting the view that a large number of rare and minute marine species may have escaped previous characterization. We found generally similar geographical patterns for abundant and rare microeukaryotic sub-communities, and both showed a significant distance-decay similarity trend. Variation partitioning showed that both rare and abundant sub-communities exhibited a slightly stronger response to environmental factors than spatial (distance) factors. However, the abundant sub-community was strongly correlated with variations in spatial, environmental and sediment grain size factors (66% of variance explained), but the rare assemblage was not (16%). This suggests that different or more complex mechanisms generate and maintain diversity in the rare biosphere in this habitat.}, } @article {pmid28879444, year = {2018}, author = {Bhargavi, SD and Praveen, VK and Anil Kumar, M and Savitha, J}, title = {Comparative Study on Whole Genome Sequences of Aspergillus terreus (Soil Fungus) and Diaporthe ampelina (Endophytic Fungus) with Reference to Lovastatin Production.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {84-91}, pmid = {28879444}, issn = {1432-0991}, support = {DST/SO/FNo.SERB.SR/SO/ PS/046/2011//Science and Engineering Research Board/ ; }, mesh = {Aspergillus/classification/*genetics/isolation & purification/metabolism ; Endophytes/*genetics/metabolism ; Fungal Proteins/genetics/metabolism ; *Genome, Fungal ; Lovastatin/*biosynthesis ; Multigene Family ; Saccharomycetales/*genetics/metabolism ; Soil Microbiology ; }, abstract = {Lovastatin is a competitive inhibitor of the enzyme hydroxymethyl glutaryl coenzyme A reductase (HMGR) in cholesterol biosynthetic pathway and hence used in the treatment of hyperlipidemia. In a previous study, we report a tropical soil isolate, Aspergillus terreus (KM017963), which produces ample amount of lovastatin than its counterpart that are endophytic in origin. Bioinformatic analysis of whole genome sequence of A. terreus (AH007774.1), a soil isolate revealed the presence of gene cluster (AF141924.1 & AF141925.1) responsible for lovastatin production, whereas endophytic fungi including a strain of A. terreus showed no homology with the lovastatin gene cluster. The molecular study was also carried out targeting PCR amplification of the two important genes, lovE (a regulatory gene) and lovF (transcriptional regulatory factor) in genomic and c-DNA of soil and endophytic fungi. Expression of the two genes was successful in A. terreus (KM017963), whereas the same was not achieved in endophytic fungi. To further validate our above findings, in the present study, the whole genome sequencing of A. terreus and a selected endophytic fungus, Diaporthe ampelina (Phomopsis) was performed. Lovastatin gene cluster, when aligned on the consensus sequence of both genomes, the entire lovastatin gene cluster was detected in a single scaffold (1.16) of A.terreus genome. On the contrary, there was a complete absence of lovastatin gene cluster in the genome of D. ampelina (an endophyte). The probable reasons for the absence of lovastatin gene cluster in endophytic fungi are discussed.}, } @article {pmid28877009, year = {2018}, author = {Purkey, SG and Smethie, WM and Gebbie, G and Gordon, AL and Sonnerup, RE and Warner, MJ and Bullister, JL}, title = {A Synoptic View of the Ventilation and Circulation of Antarctic Bottom Water from Chlorofluorocarbons and Natural Tracers.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {503-527}, doi = {10.1146/annurev-marine-121916-063414}, pmid = {28877009}, issn = {1941-0611}, abstract = {Antarctic Bottom Water (AABW) is the coldest, densest, most prolific water mass in the global ocean. AABW forms at several distinct regions along the Antarctic coast and feeds into the bottom limb of the meridional overturning circulation, filling most of the global deep ocean. AABW has warmed, freshened, and declined in volume around the globe in recent decades, which has implications for the global heat and sea level rise budgets. Over the past three decades, the use of tracers, especially time-varying tracers such as chlorofluorocarbons, has been essential to our understanding of the formation, circulation, and variability of AABW. Here, we review three decades of temperature, salinity, and tracer data and analysis that have led to our current knowledge of AABW and how the southern component of deep-ocean ventilation is changing with time.}, } @article {pmid28875241, year = {2018}, author = {Inaba, S}, title = {Primary Formation Path of Formaldehyde in Hydrothermal Vents.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {1-22}, doi = {10.1007/s11084-017-9550-5}, pmid = {28875241}, issn = {1573-0875}, support = {2017B-326//Waseda University/ ; }, mesh = {Carbon Monoxide/*chemistry ; Catalysis ; Evolution, Chemical ; Formaldehyde/*chemistry ; Formates/*chemistry ; Hydrothermal Vents ; Quantum Theory ; }, abstract = {Formaldehyde is abundant in the universe and one of the fundamental molecules for life. Hydrothermal vents produce a substantial amount of hydrogen molecules by serpentinization and promote reductive reactions of single carbon compounds. The abundance of formaldehyde is expected to be low due to the high Gibbs free energy in hydrothermal vents. We consider two competing formation pathways of formaldehyde: (1) the reduction of CO by H2 and (2) the reduction of HCOOH by H2 to form a methanediol, followed by the dehydration of the methanediol. We performed a number of quantum chemical simulations to examine the formation of formaldehyde in the gas phase as well as in aqueous solution. The energy barrier is significantly reduced by the catalytic effect of water molecules in aqueous solution and becomes lowest when a water cluster consisted of 5 water molecules catalyzes the reduction. The energy barrier to form a methanediol by the reduction of HCOOH is lower by 17.5 kcal/mol than that to form a formaldehyde by the reduction of CO. Considering the low energy barrier to dehydrate methanediol, the primary pathway to form formaldehyde in hydrothermal vents is concluded to be the reduction of HCOOH by H2, followed by the dehydration of methanediol.}, } @article {pmid28870497, year = {2018}, author = {Selbach, C and Seddon, PJ and Poulin, R}, title = {Parasites Lost: Neglecting a Crucial Element in De-Extinction.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {9-11}, doi = {10.1016/j.pt.2017.08.003}, pmid = {28870497}, issn = {1471-5007}, mesh = {Animals ; Conservation of Natural Resources ; Ethics ; *Extinction, Biological ; *Host-Parasite Interactions ; Parasites/*physiology ; }, abstract = {Bringing back iconic and beloved extinct species is a hot and intensely debated current topic. Yet, the parasites of de-extinction candidate species have remained largely overlooked in this debate. Here we point out the potentially far-reaching ecological impacts of bringing back extinct species without their parasites.}, } @article {pmid28870375, year = {2018}, author = {Rivals, F and Uno, KT and Bibi, F and Pante, MC and Njau, J and de la Torre, I}, title = {Dietary traits of the ungulates from the HWK EE site at Olduvai Gorge (Tanzania): Diachronic changes and seasonality.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {203-214}, doi = {10.1016/j.jhevol.2017.08.011}, pmid = {28870375}, issn = {1095-8606}, abstract = {The Oldowan site HWK EE (Olduvai Gorge, Tanzania) has yielded a large fossil and stone tool assemblage at the transition from Lower to Middle Bed II, ∼1.7 Ma. Integrated tooth wear and stable isotope analyses were performed on the three most abundant ungulate taxa from HWK EE, namely Alcelaphini, cf. Antidorcas recki (Antilopini) and Equus oldowayensis (Equini), to infer dietary traits in each taxon. Some paleodietary changes were observed for cf. A. recki and E. oldowayensis based on tooth wear at the transition from the Lemuta to the Lower Augitic Sandstone (LAS) interval within the HWK EE sequence. Stable carbon and oxygen isotope data show no significant changes in bulk diet or hydroclimate between the Lemuta and LAS intervals. The combined tooth wear and stable isotope data suggest similar paleoecological conditions across the two HWK EE intervals, but that differences in vegetation consumed among ungulates may have resulted in changes in dietary niches. Integrating tooth wear and stable isotope analyses permits the characterization of ungulate diets and habitats at HWK EE where C4 dominated and minor mixed C3 and C4 habitats were present. Our results provide a better understanding of the paleoenvironmental conditions of the Lemuta and LAS intervals. The LAS assemblage was mostly accumulated during relatively dry periods at Olduvai Gorge when grasses were not as readily available and grazing animals may have been more nutritionally-stressed than during the formation of the Lemuta assemblage. This helps to contextualize variations in hominin and carnivore feeding behavior observed from the faunal assemblages produced during the two main occupations of the site.}, } @article {pmid28867148, year = {2018}, author = {Ghosh, P}, title = {Variation, Indispensability, and Masking in the M protein.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {132-144}, pmid = {28867148}, issn = {1878-4380}, support = {R01 AI096837/AI/NIAID NIH HHS/United States ; }, mesh = {*Antigenic Variation ; Antigens, Bacterial/classification/genetics/*immunology/*metabolism ; Antimicrobial Cationic Peptides/metabolism ; Bacterial Outer Membrane Proteins/classification/genetics/*immunology/*metabolism ; Carrier Proteins/classification/genetics/*immunology/*metabolism ; Complement C4b-Binding Protein/metabolism ; Complement Factor H/metabolism ; Histones/metabolism ; Host-Pathogen Interactions/immunology ; Humans ; Protein Binding ; Staphylococcal Vaccines ; Streptococcus pyogenes/metabolism/pathogenicity ; Virulence Factors/metabolism ; }, abstract = {The M protein is the major surface-associated virulence factor of group A Streptococcus (GAS) and an antigenically variable target of host immunity. How selection pressures to escape immune recognition, maintain indispensable functions, and mask vulnerabilities have shaped the sequences of the >220M protein types is unclear. Recent experiments have shed light on this question by showing that, hidden within the antigenic variability of many M protein types, are sequence patterns conserved for recruiting human C4b-binding protein (C4BP). Other host factors may be recruited in a similar manner by conserved but hidden sequence patterns in the M protein. The identification of such patterns may be applicable to the development of a GAS vaccine.}, } @article {pmid28865010, year = {2018}, author = {Thammarongtham, C and Nookaew, I and Vorapreeda, T and Srisuk, T and Land, ML and Jeennor, S and Laoteng, K}, title = {Genome Characterization of Oleaginous Aspergillus oryzae BCC7051: A Potential Fungal-Based Platform for Lipid Production.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {57-70}, pmid = {28865010}, issn = {1432-0991}, support = {P-14-50613//National Center for Genetic Engineering and Biotechnology/ ; VR-2013-4504//The Swedish Research Council/ ; }, mesh = {Aspergillus oryzae/*genetics/*metabolism ; Fungal Proteins/genetics/metabolism ; *Genome, Fungal ; Lipids/*biosynthesis ; Malates/metabolism ; Synteny ; }, abstract = {The selected robust fungus, Aspergillus oryzae strain BCC7051 is of interest for biotechnological production of lipid-derived products due to its capability to accumulate high amount of intracellular lipids using various sugars and agro-industrial substrates. Here, we report the genome sequence of the oleaginous A. oryzae BCC7051. The obtained reads were de novo assembled into 25 scaffolds spanning of 38,550,958 bps with predicted 11,456 protein-coding genes. By synteny mapping, a large rearrangement was found in two scaffolds of A. oryzae BCC7051 as compared to the reference RIB40 strain. The genetic relationship between BCC7051 and other strains of A. oryzae in terms of aflatoxin production was investigated, indicating that the A. oryzae BCC7051 was categorized into group 2 nonaflatoxin-producing strain. Moreover, a comparative analysis of the structural genes focusing on the involvement in lipid metabolism among oleaginous yeast and fungi revealed the presence of multiple isoforms of metabolic enzymes responsible for fatty acid synthesis in BCC7051. The alternative routes of acetyl-CoA generation as oleaginous features and malate/citrate/pyruvate shuttle were also identified in this A. oryzae strain. The genome sequence generated in this work is a dedicated resource for expanding genome-wide study of microbial lipids at systems level, and developing the fungal-based platform for production of diversified lipids with commercial relevance.}, } @article {pmid28861662, year = {2018}, author = {Magaña-Ortíz, D and Fernández, F and Loske, AM and Gómez-Lim, MA}, title = {Extracellular Expression in Aspergillus niger of an Antibody Fused to Leishmania sp. Antigens.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {40-48}, pmid = {28861662}, issn = {1432-0991}, mesh = {Antibodies, Protozoan/*genetics/metabolism ; Antigens, Protozoan/*genetics/metabolism ; Aspergillus niger/*genetics/metabolism ; *Gene Expression ; Leishmania/*enzymology/genetics ; Methyltransferases/genetics ; N-Glycosyl Hydrolases/genetics/metabolism ; Protozoan Proteins/genetics/metabolism ; Recombinant Fusion Proteins/genetics/metabolism ; Xylose/metabolism ; }, abstract = {Nucleoside hydrolase and sterol 24-c-methyltransferase, two antigenic proteins of Leishmania sp., were expressed in Aspergillus niger. Genetic transformation of conidia was achieved using underwater shock waves. scFv antibody addressed to DEC205, a receptor of dendritic cells, was fused to two proteins of Leishmania sp. Receptor 205 has a relevant role in the immune system in mammals; it can modulate T cell response to different antigens. Extracellular expression strategy of recombinant antibody was achieved using a fragment of native glucoamylase A (514 aa) as a carrier. Fermentations in shake flasks showed that the recombinant protein (104 kDa) was expressed and secreted only when maltose was used as carbon source; on the contrary, the expression was highly repressed in presence of xylose. Noteworthy, recombinant protein was secreted without glucoamylase-carrier and accumulation at intracellular level was not observed. The results presented here demonstrate the high value of Aspergillus niger as biotechnological platform for recombinant antibodies against Leishmania sp. at low cost. To the best of our knowledge, this is the first report about the recombinant expression of antigenic proteins of Leishmania sp. in filamentous fungi. The protein obtained can be used to explore novel strategies to induce immunity against Leishmania sp. or it can be employed in diagnostic kits to detect this neglected disease.}, } @article {pmid28856411, year = {2018}, author = {Aguech-Oueslati, L and Jaidane, H and Sane, F and Jrad-Battikh, N and Hamed, SB and Hober, D and Gharbi, J}, title = {Evaluation of Contamination Risks with Coxsackievirus B4 E2 in Swiss Albino Mice Stools.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {32-39}, pmid = {28856411}, issn = {1432-0991}, mesh = {Animals ; Antibodies, Neutralizing/immunology ; Antibodies, Viral/immunology ; Coxsackievirus Infections/immunology/*veterinary/virology ; Enterovirus/classification/genetics/immunology/*isolation & purification ; Feces/*virology ; Female ; Mice ; Pancreas/immunology/virology ; Rodent Diseases/immunology/*virology ; Spleen/immunology/virology ; }, abstract = {Coxsackie B4 (CV-B4), is a major cause of viral myocarditis, dilated cardiomyopathy, and pancreatitis. Like other human enteroviruses, CV-B4 is ubiquitous, excreted in the stool, transmitted by fecal-oral route, and persists in the environment. In the context of studies on CV-B4 infection, it is important to investigate how this virus can be eliminated and to show the possibility of contamination risk with a CV-B4 E2 infected Swiss albino mice. Swiss albino female mice were inoculated with CV-B4 E2 strain and divided in two groups: the first was intraperitoneally (I.P.) infected; the second was orally infected. In order to study the CV-B4 E2 infection in mice, total RNA was extracted from thymus, spleen, pancreas, and intestine, and viral genome was detected using semi-nested (RT-PCR). To further demonstrate infection or immunization of mice, Sera obtained from infected mice were assayed in vitro for their neutralizing antibody. To detect virus in stool of infected mice, stool samples were collected at different post-infection (p.i.) times. Neutralizing antibodies were detectable all along the follow-up period (Day 0, 1, 3, 7, 9, 17, 22, 30, 45, 60 p.i.) in I.P and oral infected mice. Our results showed that when mice were inoculated successively at day 0 and day 8, neutralizing activity was increased in I.P route more than in the oral route. Viral isolation in HEp-2 cells showed negative results. Stool viral analyses reveal a low detection of the CV-B4 E2 genome for all infected mice. In conclusion, our experiments demonstrated that there are no risks linked with the stool of CV-B4 E2 of Swiss albino mice. It would be interesting to characterize the inhibitors of the virus infectivity in these biological samples (stool) and investigate their targets and mechanisms of action.}, } @article {pmid28853998, year = {2018}, author = {Moreno, AR and Martiny, AC}, title = {Ecological Stoichiometry of Ocean Plankton.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {43-69}, doi = {10.1146/annurev-marine-121916-063126}, pmid = {28853998}, issn = {1941-0611}, abstract = {Marine plankton elemental stoichiometric ratios can deviate from the Redfield ratio (106C:16N:1P); here, we examine physiological and biogeochemical mechanisms that lead to the observed variation across lineages, regions, and seasons. Many models of ecological stoichiometry blend together acclimative and adaptive responses to environmental conditions. These two pathways can have unique molecular mechanisms and stoichiometric outcomes, and we attempt to disentangle the two processes. We find that interactions between environmental conditions and cellular growth are key to understanding stoichiometric regulation, but the growth rates of most marine plankton populations are poorly constrained. We propose that specific physiological mechanisms have a strong impact on plankton and community stoichiometry in nutrient-rich environments, whereas biogeochemical interactions are important for the stoichiometry of the oligotrophic gyres. Finally, we outline key areas with missing information that is needed to advance understanding of the present and future ecological stoichiometry of ocean plankton.}, } @article {pmid28853997, year = {2018}, author = {Humphris, SE and Klein, F}, title = {Progress in Deciphering the Controls on the Geochemistry of Fluids in Seafloor Hydrothermal Systems.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {315-343}, doi = {10.1146/annurev-marine-121916-063233}, pmid = {28853997}, issn = {1941-0611}, abstract = {Over the last four decades, more than 500 sites of seafloor hydrothermal venting have been identified in a range of tectonic environments. These vents represent the seafloor manifestation of hydrothermal convection of seawater through the permeable oceanic basement that is driven by a subsurface heat source. Hydrothermal circulation has fundamental effects on the transfer of heat and mass from the lithosphere to the hydrosphere, the composition of seawater, the physical and chemical properties of the oceanic basement, and vent ecosystems at and below the seafloor. In this review, we compare and contrast the vent fluid chemistry from hydrothermal fields in a range of tectonic settings to assess the relative roles of fluid-mineral equilibria, phase separation, magmatic input, seawater entrainment, and sediment cover in producing the observed range of fluid compositions. We focus particularly on hydrothermal activity in those tectonic environments (e.g., mid-ocean ridge detachment faults, back-arc basins, and island arc volcanoes) where significant progress has been made in the last decade in documenting the variations in vent fluid composition.}, } @article {pmid28852850, year = {2018}, author = {Park, SN and Lim, YK and Choi, MH and Cho, E and Bang, IS and Kim, JM and Ahn, SJ and Kook, JK}, title = {Antimicrobial Mechanism of Oleanolic and Ursolic Acids on Streptococcus mutans UA159.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {11-19}, pmid = {28852850}, issn = {1432-0991}, support = {A091074//Korea Healthcare Technology R&D Project, Ministry for Health, Welfare and Family Affairs, Republic of Korea/ ; 2017M3A9B8065844//The Bio & Medical Technology Development Program of the National Research Foundation (NRF) funded by the Ministry of Science, ICT & Future Planning./ ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacterial Proteins/genetics/metabolism ; Gene Expression Regulation, Bacterial/drug effects ; Oleanolic Acid/*pharmacology ; Streptococcus mutans/*drug effects/genetics/metabolism ; Triterpenes/*pharmacology ; }, abstract = {Triterpenoid saponin derivatives oleanolic acid (OA) and ursolic acid (UA), but not betulinic acid (BA), were previously found to have strong antimicrobial activity against Streptococcus mutans. OA and UA inhibited the transcription of genes related to peptidoglycan biosynthesis, thereby preventing bacterial growth. However, it is not clear whether this is the only pathway involved in the antimicrobial activity of these compounds against S. mutans. Therefore, we used quantitative real-time PCR (qPCR) and microarray analyses to examine the expression of genes related to essential metabolic pathways in S. mutans UA159 following incubation with OA, UA, or BA. An oligonucleotide array consisting of 5363 probes was designed to survey 1928 of the 1963 genes in the genome of S. mutans UA159. Genes that showed >2-fold changes in expression in response to the treatment conditions were annotated, and selected target genes involved in central metabolism were analyzed by qPCR. Microarray analysis confirmed that the gene expression patterns of the OA- and UA-treated cells differed from that of the BA-treated culture, indicating differences in the antimicrobial mechanism. In particular, the expression of pfk and pykF, coding for glycolysis regulatory proteins phosphofructokinase and pyruvate kinase, respectively, were significantly decreased in the OA and UA groups (P < 0.05), as were genes involved in fatty acid and amino acid synthesis. In addition, the microarray analysis confirmed previous qPCR results showing that peptidoglycan synthesis is down-regulated in the OA- and UA-treated groups. OA and UA also appear to decrease the generation of organic acids by S. mutans UA159, which would have an anticaries effect. Overall, these findings suggest that OA and UA affect multiple genes involved in the central metabolism of S. mutans, with inhibition of glycolysis, fatty acid synthesis, amino acid synthesis, and peptidoglycan synthesis, all contributing to their antimicrobial activity.}, } @article {pmid28851748, year = {2018}, author = {Szymborska, A and Gerhardt, H}, title = {Hold Me, but Not Too Tight-Endothelial Cell-Cell Junctions in Angiogenesis.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a029223}, pmid = {28851748}, issn = {1943-0264}, abstract = {Endothelial cell-cell junctions must perform seemingly incompatible tasks during vascular development-providing stable connections that prevent leakage, while allowing dynamic cellular rearrangements during sprouting, anastomosis, lumen formation, and functional remodeling of the vascular network. This review aims to highlight recent insights into the molecular mechanisms governing endothelial cell-cell adhesion in the context of vascular development.}, } @article {pmid28851747, year = {2018}, author = {Lampugnani, MG and Dejana, E and Giampietro, C}, title = {Vascular Endothelial (VE)-Cadherin, Endothelial Adherens Junctions, and Vascular Disease.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a029322}, pmid = {28851747}, issn = {1943-0264}, abstract = {Endothelial cell-cell adherens junctions (AJs) supervise fundamental vascular functions, such as the control of permeability and transmigration of circulating leukocytes, and the maintenance of existing vessels and formation of new ones. These processes are often dysregulated in pathologies. However, the evidence that links dysfunction of endothelial AJs to human pathologies is mostly correlative. In this review, we present an update of the molecular organization of AJ complexes in endothelial cells (ECs) that is mainly based on observations from experimental models. Furthermore, we report in detail on a human pathology, cerebral cavernous malformation (CCM), which is initiated by loss-of-function mutations in the genes that encode the three cytoplasmic components of AJs (CCM1, CCM2, and CCM3). At present, these represent a unique example of mutations in components of endothelial AJs that cause human disease. We describe also how studies into the defects of AJs in CCM are shedding light on the crucial regulatory mechanisms and signaling activities of these endothelial structures. Although these observations are specific for CCM, they support the concept that dysfunction of endothelial AJs can directly contribute to human pathologies.}, } @article {pmid28850950, year = {2018}, author = {Freire, AV and Grinspon, RP and Rey, RA}, title = {Importance of Serum Testicular Protein Hormone Measurement in the Assessment of Disorders of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {30-40}, doi = {10.1159/000479572}, pmid = {28850950}, issn = {1661-5433}, mesh = {Disorders of Sex Development/*blood/*diagnosis/physiopathology ; Fetus/metabolism ; Humans ; Sex Differentiation ; Testicular Hormones/*blood ; }, abstract = {Commonly known for testosterone secretion, the testes also produce the protein hormones anti-müllerian hormone (AMH), inhibin B, and insulin-like factor 3 (INSL3). AMH and inhibin B are secreted by Sertoli cells, whereas INSL3 is a Leydig cell product. AMH is involved in fetal sex differentiation and induces the regression of the anlagen of the uterus and fallopian tubes. INSL3 participates in fetal testicular descent. Serum testicular protein hormone assessment can be very useful and complementary to testosterone measurements in patients with DSD. AMH and inhibin B determination is extremely helpful during childhood, when basal testosterone is normally low. Serum AMH and inhibin B above the female range are indicative of the presence of testicular tissue, and their circulating levels reflect the amount of functional Sertoli cells. In DSD patients with normal male levels of AMH and inhibin B, the diagnosis of gonadal dysgenesis can be ruled out, and isolated androgen secretion deficiency or androgen insensitivity should be suspected. In externally virilized XY patients with persistent müllerian ducts, serum AMH levels determine the diagnosis to AMH deficiency or resistance. At pubertal age, inhibin B levels serve to predict spermatogenic development.}, } @article {pmid28848186, year = {2018}, author = {Guerra-Junior, G and Andrade, KC and Barcelos, IHK and Maciel-Guerra, AT}, title = {Imaging Techniques in the Diagnostic Journey of Disorders of Sex Development.}, journal = {Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation}, volume = {12}, number = {1-3}, pages = {95-99}, doi = {10.1159/000479453}, pmid = {28848186}, issn = {1661-5433}, mesh = {Diagnostic Imaging/*methods ; Disorders of Sex Development/*diagnosis/*diagnostic imaging ; Humans ; Magnetic Resonance Imaging ; Prenatal Diagnosis ; Tomography, X-Ray Computed ; Ultrasonography ; }, abstract = {Various disorders of sex development (DSD) result in an abnormal development of genitalia that may be recognized at prenatal ultrasonography, immediately after birth, or later in life. Because of the complex nature of DSD, the participation of a multidisciplinary team, including imaging or radiology technologists, is required to address the patient's medical needs. The first steps in the management of DSD are sex evaluation, which is based on factors such as the genotype, the presence, location, and appearance of reproductive organs, the potential for fertility, and the cultural background and beliefs of the patient's family. It is also important to ensure the detection of comorbidity (as in syndromes) and to define the etiology of DSD in order to offer the best prognosis. Ultrasonography is the primary modality for demonstrating internal organs, genitography is used to assess the urethra, vagina, and any fistulas, and magnetic resonance imaging is used as an additional modality to assess internal gonads and genitalia. This review presents the advantages and disadvantages and the sensitivity and specificity for each type of radiological imaging to help in the evaluation of DSD cases before and after birth.}, } @article {pmid28847903, year = {2018}, author = {Zhu, J}, title = {T Helper Cell Differentiation, Heterogeneity, and Plasticity.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a030338}, pmid = {28847903}, issn = {1943-0264}, support = {Z99 AI999999/NULL/Intramural NIH HHS/United States ; ZIA AI001169-07/NULL/Intramural NIH HHS/United States ; }, abstract = {Naïve CD4 T cells, on activation, differentiate into distinct T helper (Th) subsets that produce lineage-specific cytokines. By producing unique sets of cytokines, effector Th subsets play critical roles in orchestrating immune responses to a variety of infections and are involved in the pathogenesis of many inflammatory diseases including autoimmunity, allergy, and asthma. The differentiation of Th cells relies on the strength of T-cell receptor (TCR) signaling and signals triggered by polarizing cytokines that activate and/or up-regulate particular transcription factors. Several lineage-specific master transcription factors dictate Th cell fates and functions. Although these master regulators cross-regulate each other, their expression can be dynamic. Sometimes, they are even coexpressed, resulting in massive Th-cell heterogeneity and plasticity. Similar regulation mediated by these master regulators is also found in innate lymphoid cells (ILCs) that are innate counterparts of Th cells.}, } @article {pmid28847902, year = {2018}, author = {Jaiganesh, A and Narui, Y and Araya-Secchi, R and Sotomayor, M}, title = {Beyond Cell-Cell Adhesion: Sensational Cadherins for Hearing and Balance.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, pmid = {28847902}, issn = {1943-0264}, support = {R00 DC012534/DC/NIDCD NIH HHS/United States ; R01 DC015271/DC/NIDCD NIH HHS/United States ; }, abstract = {Cadherins form a large family of proteins often involved in calcium-dependent cellular adhesion. Although classical members of the family can provide a physical bond between cells, a subset of special cadherins use their extracellular domains to interlink apical specializations of single epithelial sensory cells. Two of these cadherins, cadherin-23 (CDH23) and protocadherin-15 (PCDH15), form extracellular "tip link" filaments that connect apical bundles of stereocilia on hair cells essential for inner-ear mechanotransduction. As these bundles deflect in response to mechanical stimuli from sound or head movements, tip links gate hair-cell mechanosensitive channels to initiate sensory perception. Here, we review the unusual and diverse structural properties of these tip-link cadherins and the functional significance of their deafness-related missense mutations. Based on the structural features of CDH23 and PCDH15, we discuss the elasticity of tip links and models that bridge the gap between the nanomechanics of cadherins and the micromechanics of hair-cell bundles during inner-ear mechanotransduction.}, } @article {pmid28847901, year = {2018}, author = {Oppenheim, JJ}, title = {The Future of the Cytokine Discipline.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a028498}, pmid = {28847901}, issn = {1943-0264}, abstract = {The study of cytokines has evolved from the detection of functional activities present in tissue culture supernatants to the characterization of the three-dimensional molecular structures of the cytokines and their receptors. Investigators studying cytokines need to have specialized expertise in using cytokine assays, assessing their receptor interactions, signal transduction, gene activation, and biological effects, and in the therapeutic utilization of agonists and antagonists. Cytokinology can therefore be considered a discipline. In this article, I have considered studies leading to the identification of novel cytokines, potential producers of cytokine mimics such as viruses and the microbiome, and the complex interactions of the cytokine network with our vital functions. Our ever-increasing success in using cytokines and, in particular, cytokine inhibitors therapeutically suggest that cytokinology will eventually become an independent discipline.}, } @article {pmid28847900, year = {2018}, author = {Beamish, IV and Hinck, L and Kennedy, TE}, title = {Making Connections: Guidance Cues and Receptors at Nonneural Cell-Cell Junctions.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {11}, pages = {}, doi = {10.1101/cshperspect.a029165}, pmid = {28847900}, issn = {1943-0264}, abstract = {The field of axon guidance was revolutionized over the past three decades by the identification of highly conserved families of guidance cues and receptors. These proteins are essential for normal neural development and function, directing cell and axon migration, neuron-glial interactions, and synapse formation and plasticity. Many of these genes are also expressed outside the nervous system in which they influence cell migration, adhesion and proliferation. Because the nervous system develops from neural epithelium, it is perhaps not surprising that these guidance cues have significant nonneural roles in governing the specialized junctional connections between cells in polarized epithelia. The following review addresses roles for ephrins, semaphorins, netrins, slits and their receptors in regulating adherens, tight, and gap junctions in nonneural epithelia and endothelia.}, } @article {pmid28847899, year = {2018}, author = {Wallach, D}, title = {The Tumor Necrosis Factor Family: Family Conventions and Private Idiosyncrasies.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {10}, pages = {}, doi = {10.1101/cshperspect.a028431}, pmid = {28847899}, issn = {1943-0264}, abstract = {The tumor necrosis factor (TNF) cytokine family and the TNF/nerve growth factor (NGF) family of their cognate receptors together control numerous immune functions, as well as tissue-homeostatic and embryonic-development processes. These diverse functions are dictated by both shared and distinct features of family members, and by interactions of some members with nonfamily ligands and coreceptors. The spectra of their activities are further expanded by the occurrence of the ligands and receptors in both membrane-anchored and soluble forms, by "re-anchoring" of soluble forms to extracellular matrix components, and by signaling initiation via intracellular domains (IDs) of both receptors and ligands. Much has been learned about shared features of the receptors as well as of the ligands; however, we still have only limited knowledge of the mechanistic basis for their functional heterogeneity and for the differences between their functions and those of similarly acting cytokines of other families.}, } @article {pmid28846492, year = {2018}, author = {Morgan, SG and Shanks, AL and MacMahan, JH and Reniers, AJHM and Feddersen, F}, title = {Planktonic Subsidies to Surf-Zone and Intertidal Communities.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {345-369}, doi = {10.1146/annurev-marine-010816-060514}, pmid = {28846492}, issn = {1941-0611}, abstract = {Plankton are transported onshore, providing subsidies of food and new recruits to surf-zone and intertidal communities. The transport of plankton to the surf zone is influenced by wind, wave, and tidal forcing, and whether they enter the surf zone depends on alongshore variation in surf-zone hydrodynamics caused by the interaction of breaking waves with coastal morphology. Areas with gently sloping shores and wide surf zones typically have orders-of-magnitude-higher concentrations of plankton in the surf zone and dense larval settlement in intertidal communities because of the presence of bathymetric rip currents, which are absent in areas with steep shores and narrow surf zones. These striking differences in subsidies have profound consequences; areas with greater subsidies support more productive surf-zone communities and possibly more productive rocky intertidal communities. Recognition of the importance of spatial subsidies for rocky community dynamics has recently advanced ecological theory, and incorporating surf-zone hydrodynamics would be an especially fruitful line of investigation.}, } @article {pmid28846438, year = {2018}, author = {Chilton, MD}, title = {My Secret Life.}, journal = {Annual review of plant biology}, volume = {69}, number = {}, pages = {1-20}, doi = {10.1146/annurev-arplant-032717-090606}, pmid = {28846438}, issn = {1545-2123}, abstract = {In my early childhood, my parents gave me to my maternal grandparents for a "visit" that extended over a period of nine years. I seemed to be a fairly ordinary student in primary grades, and had to take a remedial general science class upon entering high school, my first exposure to science. It was the teacher of that class, Mr. Auer, who told me that I had scored amazingly high on a science aptitude test given to all freshmen. The people who administered the testing were convinced that I must have cheated somehow. Mr. Auer suggested that I might want to consider a career in science if I liked it. I loved it, and I did. This autobiographical article recounts my changing interests as I became aware of new fields of science during my education and the start of my career. Out of basic studies of a microbe that causes plant cancer, we developed a method to engineer new and useful genes into crop plants.}, } @article {pmid28844447, year = {2018}, author = {Younes, JA and Lievens, E and Hummelen, R and van der Westen, R and Reid, G and Petrova, MI}, title = {Women and Their Microbes: The Unexpected Friendship.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {16-32}, doi = {10.1016/j.tim.2017.07.008}, pmid = {28844447}, issn = {1878-4380}, mesh = {Biofilms ; Breast/microbiology ; Dysbiosis/microbiology ; Fallopian Tubes/microbiology ; Female ; Fertilization ; Gastrointestinal Microbiome/immunology/*physiology ; Gastrointestinal Tract/microbiology ; Health ; Humans ; Infant ; Infant Health ; Male ; Microbiota/immunology/*physiology ; Placenta/microbiology ; Pregnancy ; Probiotics ; Reproductive Health ; Uterus/microbiology ; Vagina/immunology/*microbiology ; }, abstract = {Communities of microbiota have been associated with numerous health outcomes, and while much emphasis has been placed on the gastrointestinal niche, there is growing interest in the microbiome specific for female reproductive health and the health of their offspring. The vaginal microbiome plays an essential role not only in health and dysbiosis, but also potentially in successful fertilization and healthy pregnancies. In addition, microbial communities have been isolated from formerly forbidden sterile niches such as the placenta, breast, uterus, and Fallopian tubes, strongly suggesting an additional microbial role in women's health. A combination of maternally linked prenatal, birth, and postnatal factors, together with environmental and medical interventions, influence early and later life through the microbiome. Here, we review the role of microbes in female health focusing on the vaginal tract and discuss how male and female reproductive microbiomes are intertwined with conception and how mother-child microbial transfer is a key determinant in infant health, and thus the next generation.}, } @article {pmid28841344, year = {2018}, author = {Brown, MS and Radhakrishnan, A and Goldstein, JL}, title = {Retrospective on Cholesterol Homeostasis: The Central Role of Scap.}, journal = {Annual review of biochemistry}, volume = {87}, number = {}, pages = {783-807}, pmid = {28841344}, issn = {1545-4509}, support = {P01 HL020948/HL/NHLBI NIH HHS/United States ; }, abstract = {Scap is a polytopic membrane protein that functions as a molecular machine to control the cholesterol content of membranes in mammalian cells. In the 21 years since our laboratory discovered Scap, we have learned how it binds sterol regulatory element-binding proteins (SREBPs) and transports them from the endoplasmic reticulum (ER) to the Golgi for proteolytic processing. Proteolysis releases the SREBP transcription factor domains, which enter the nucleus to promote cholesterol synthesis and uptake. When cholesterol in ER membranes exceeds a threshold, the sterol binds to Scap, triggering several conformational changes that prevent the Scap-SREBP complex from leaving the ER. As a result, SREBPs are no longer processed, cholesterol synthesis and uptake are repressed, and cholesterol homeostasis is restored. This review focuses on the four domains of Scap that undergo concerted conformational changes in response to cholesterol binding. The data provide a molecular mechanism for the control of lipids in cell membranes.}, } @article {pmid28838563, year = {2018}, author = {Brassey, CA and O'Mahoney, TG and Chamberlain, AT and Sellers, WI}, title = {A volumetric technique for fossil body mass estimation applied to Australopithecus afarensis.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {47-64}, doi = {10.1016/j.jhevol.2017.07.014}, pmid = {28838563}, issn = {1095-8606}, abstract = {Fossil body mass estimation is a well established practice within the field of physical anthropology. Previous studies have relied upon traditional allometric approaches, in which the relationship between one/several skeletal dimensions and body mass in a range of modern taxa is used in a predictive capacity. The lack of relatively complete skeletons has thus far limited the potential application of alternative mass estimation techniques, such as volumetric reconstruction, to fossil hominins. Yet across vertebrate paleontology more broadly, novel volumetric approaches are resulting in predicted values for fossil body mass very different to those estimated by traditional allometry. Here we present a new digital reconstruction of Australopithecus afarensis (A.L. 288-1; 'Lucy') and a convex hull-based volumetric estimate of body mass. The technique relies upon identifying a predictable relationship between the 'shrink-wrapped' volume of the skeleton and known body mass in a range of modern taxa, and subsequent application to an articulated model of the fossil taxa of interest. Our calibration dataset comprises whole body computed tomography (CT) scans of 15 species of modern primate. The resulting predictive model is characterized by a high correlation coefficient (r2 = 0.988) and a percentage standard error of 20%, and performs well when applied to modern individuals of known body mass. Application of the convex hull technique to A. afarensis results in a relatively low body mass estimate of 20.4 kg (95% prediction interval 13.5-30.9 kg). A sensitivity analysis on the articulation of the chest region highlights the sensitivity of our approach to the reconstruction of the trunk, and the incomplete nature of the preserved ribcage may explain the low values for predicted body mass here. We suggest that the heaviest of previous estimates would require the thorax to be expanded to an unlikely extent, yet this can only be properly tested when more complete fossils are available.}, } @article {pmid28836372, year = {2018}, author = {Loxdale, HD and Balog, A}, title = {Aphid specialism as an example of ecological-evolutionary divergence.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {642-657}, doi = {10.1111/brv.12361}, pmid = {28836372}, issn = {1469-185X}, abstract = {Debate still continues around the definition of generalism and specialism in nature. To some, generalism is equated solely with polyphagy, but this cannot be readily divorced from other essential biological factors, such as morphology, behaviour, genetics, biochemistry, chemistry and ecology, including chemical ecology. Viewed in this light, and accepting that when living organisms evolve to fill new ecological-evolutionary niches, this is the primal act of specialisation, then perhaps all living organisms are specialist in the broadest sense. To illustrate the levels of specialisation that may be found in a group of animals, we here provide an overview of those displayed by a subfamily of hemipteran insects, the Aphididae, which comprises some 1600 species/subspecies in Europe alone and whose members are specialised in a variety of lifestyle traits. These include life cycle, host adaptation, dispersal and migration, associations with bacterial symbionts (in turn related to host adaptation and resistance to hymenopterous wasp parasitoids), mutualisms with ants, and resistance to insecticides. As with polyphagy, these traits cannot easily be separated from one another, but rather, are interconnected, often highly so, which makes the Aphididae a fascinating animal group to study, providing an informative, perhaps unique, model to illustrate the complexities of defining generalism versus specialism.}, } @article {pmid28835337, year = {2018}, author = {Machado, G and Wolff, JO}, title = {The assassination of a hypothesis by non-critical interpretation of molecular data: A comment on.}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {346-348}, doi = {10.1016/j.ympev.2017.06.006}, pmid = {28835337}, issn = {1095-9513}, abstract = {In a recent paper, Sharma et al. (2017) tested the hypothesis that eggs attached to males' legs in podoctid harvestmen are laid by conspecifics. Using molecular methods, they falsify the "paternal care hypothesis" and suggest that the eggs belong to spiders. Here we raise several criticisms to the authenticity of this finding and present arguments supporting the hypothesis that eggs belong to harvestmen and are not accidentally attached to the males. We argue that the falsification of the paternal care hypothesis in podoctids is premature and based on non-critical interpretation of molecular data.}, } @article {pmid28834700, year = {2018}, author = {Bowie, RCK and Pasquet, E and McEntee, JP and Njilima, F and Fjeldså, J}, title = {The systematics and biogeography of African tailorbirds (Cisticolidae: Artisornis) with comment on the choice of Bayesian branch-length prior when analyzing heterogeneous data.}, journal = {Molecular phylogenetics and evolution}, volume = {118}, number = {}, pages = {172-183}, doi = {10.1016/j.ympev.2017.08.011}, pmid = {28834700}, issn = {1095-9513}, mesh = {Animals ; Bayes Theorem ; DNA, Mitochondrial/genetics ; Genetic Loci ; Mozambique ; Passeriformes/*classification/genetics ; Phylogeny ; *Phylogeography ; *Statistics as Topic ; Tanzania ; }, abstract = {The Long-billed Tailorbird (Artisornis moreaui), one of Africa's rarest birds, has a strikingly disjunct distribution, the origin of which has long puzzled biogeographers. One small population (subspecies moreaui) occurs in sub-montane forest in the East Usambara Mountains, a sky island near the coast of northern Tanzania, and another (subspecies sousae) on Serra Jeci in northwestern Mozambique, 950km away. The African Tailorbird, the putative sister-species of Long-billed Tailorbird, also occurs in the East Usambara Mountains and on Serra Jeci, but in addition occupies all the Eastern Arc Mountain forests between these disjunct sites. Stuart (1981) hypothesized that the two tailorbird distributions could be explained by strong ecological competition, with African Tailorbird populations having eliminated Long-billed Tailorbird populations via competitive exclusion in montane forests between the East Usambara and Serra Jeci. If such competitive exclusion explains these geographic distributions, the co-occurrence of the two species in the East Usambara and at Serra Jeci may be ephemeral, with the status of Long-billed Tailorbird especially in doubt. We sought to (1) determine whether the two species of African tailorbirds are indeed sister-species, and (2) test predictions from Stuart's (1981) competitive exclusion hypothesis using genetic data. Phylogenetic analyses of our seven gene dataset (3 mtDNA, 4 introns; 4784bp) indeed place these two species together in the genus Artisornis. Instead of finding shallow divergence among African Tailorbird populations and deep divergence between Long-billed Tailorbird populations as expected from Stuart's hypothesis, we recover deep genetic divergence and geographic structure among populations of both tailorbird species. This result is consistent with long-term co-existence of the two species at East Usambara and Serra Jeci. Observational data from both the East Usambara and Serra Jeci suggest that the two species have diverged in use of forest canopy strata. From a conservation standpoint, our results suggest that extinction of the Long-billed Tailorbird as a function of competition with African Tailorbird is highly unlikely, and should not be viewed as imminent. Threats to its survival are instead anthropogenic, and conservation measures should take this into account. Finally, our empirical results suggest that mis-specification of the branch-length prior in Bayesian analyses of mitochondrial DNA data can have a profound effect on the overall tree-length (sum of branch-lengths), whereas the topology and support values tend to remain more stable. In contrast, mis-specification of the branch-length prior had a lesser impact on all aspects of the nuclear-only DNA analyses. This problem may be exacerbated when mitochondrial and nuclear DNA analyses are combined in a total evidence approach.}, } @article {pmid28831596, year = {2018}, author = {Tang, J and Jia, J and Chen, Y and Huang, X and Zhang, X and Zhao, L and Hu, W and Wang, C and Lin, C and Wu, Z}, title = {Proteomic Analysis of Vibrio parahaemolyticus Under Cold Stress.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {20-26}, pmid = {28831596}, issn = {1432-0991}, support = {2012AA101605//Chinese State High-Tech Development Plan/ ; 2012IK305//Science Foundation of General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China/ ; 2013IK175//Science Foundation of General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China/ ; 2016IK198//Science Foundation of General Administration of Quality Supervision, Inspection and Quarantine of the People's Republic of China/ ; }, mesh = {Bacterial Proteins/*chemistry/genetics/metabolism ; Cold Temperature ; Gene Expression Profiling ; Humans ; Mass Spectrometry ; Proteome/chemistry/genetics/metabolism ; Proteomics ; Vibrio Infections/microbiology ; Vibrio parahaemolyticus/chemistry/genetics/isolation & purification/*metabolism ; }, abstract = {Vibrio parahaemolyticus is a kind of food-borne pathogenic bacterium, which can seriously infect food, especially seafood causing gastroenteritis and other disease. We studied the global proteome responses of V. parahaemolyticus under cold stress by nano-liquid chromatography-tandem mass spectrometry to improve the present understanding of V. parahaemolyticus proteomics events under cold stress. A total of 1151 proteins were identified and 101 proteins were differentially expressed, of which 69 were significantly up-regulated and 32 were downregulated. Functional categorization of these proteins revealed distinct differences between cold-stressed and control cells. These proteins were grouped into 21 functional categories by the clusters of orthologous groups (COG) analysis. The most of up-regulated proteins were functionally categorized as nucleotide transport and metabolism, transcription, function unknown, and defense mechanisms. These up-regulated proteins play an important role under cold stress.}, } @article {pmid28831561, year = {2018}, author = {Cheng, M and Li, Y and Ma, Y and Qiu, J and Yan, X and He, J}, title = {Complete Genome Sequence of Sphingobium baderi DE-13, an Alkyl-Substituted Aniline-Mineralizing Bacterium.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {27-31}, pmid = {28831561}, issn = {1432-0991}, support = {31270157//National Natural Science Foundation of China/ ; 31470225//National Natural Science Foundation of China/ ; 31500082//National Natural Science Foundation of China/ ; }, mesh = {Aniline Compounds/chemistry/*metabolism ; Base Composition ; *Genome, Bacterial ; Plasmids/genetics/metabolism ; Sewage/microbiology ; Sphingomonadaceae/classification/*genetics/isolation & purification/metabolism ; }, abstract = {Alkyl-substituted aniline is an important aniline derivative that may be associated with serious environmental risks. Previously, Sphingobium baderi DE-13, a bacterium that can mineralize alkyl substituted anilines such as 2,6-dimethylaniline, 2,6-diethylaniline, 2-methyl-6-ethylaniline, 2-methylaniline, and 2-ethylaniline, was isolated from active sludge. Here, we report the complete genome sequence of strain DE-13. It contains one circular chromosome and eight circular plasmids with total 4,583,422 bp and GC content of 62.41%. The reported and predicted genes involved in the catabolism of alkyl-substituted anilines are indicated. This study will provide insights into the bacterial catabolism of alkyl substituted anilines.}, } @article {pmid28831549, year = {2018}, author = {Li, Y and Zhou, Y and Lü, ZZ and Cui, HL}, title = {Halobium Salinum sp. nov., Isolated from a Marine Solar Saltern.}, journal = {Current microbiology}, volume = {75}, number = {1}, pages = {6-10}, pmid = {28831549}, issn = {1432-0991}, support = {31370054//National Natural Science Foundation of China/ ; }, mesh = {Base Composition ; China ; DNA, Archaeal/genetics ; Euryarchaeota/classification/genetics/*isolation & purification/metabolism ; Phylogeny ; Seawater/*microbiology ; Sodium Chloride/metabolism ; }, abstract = {A halophilic archaeal strain YJ-8-ST was isolated from Yangjiang marine solar saltern, China. Cells from strain YJ-8-ST were pleomorphic, lysed in distilled water, stained Gram-negative, and formed red-pigmented colonies on agar plate. Optimal growth of the strain was obtained at 3.1 M NaCl (range 1.4-4.8 M), 0.1 M MgCl2 (range 0.005-1.0 M), 37 °C (range 20-50 °C), and pH 7.5 (range 5.5-9.5). The major polar lipids are phosphatidylglycerol (PG), phosphatidylglycerol phosphate methyl ester (PGP-Me), sulfated mannosyl glucosyl diether (S-DGD-1), and mannosyl glucosyl diether (DGD-1). The 16S rRNA gene and rpoB' gene of strain YJ-8-ST were phylogenetically related to the corresponding genes of Halobium palmae (96.9-97.2 and 92.7% similarities, respectively). The DNA G+C content of strain YJ-8-ST was determined to be 68.9 mol%. The phenotypic, chemotaxonomic, and phylogenetic characteristics suggested that strain YJ-8-ST (=CGMCC 1.12553T = JCM 30029T) represents a new species of Halobium, for which the name Halobium salinum sp. nov. is proposed.}, } @article {pmid28826642, year = {2018}, author = {Moissl-Eichinger, C and Pausan, M and Taffner, J and Berg, G and Bang, C and Schmitz, RA}, title = {Archaea Are Interactive Components of Complex Microbiomes.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {70-85}, doi = {10.1016/j.tim.2017.07.004}, pmid = {28826642}, issn = {1878-4380}, mesh = {Animals ; Archaea/classification/*physiology ; Biodiversity ; Biofilms ; Ecology ; Ecosystem ; Eukaryota ; Euryarchaeota ; Gastrointestinal Microbiome ; Gastrointestinal Tract/microbiology ; Halobacteriales ; Health ; Humans ; Microbial Consortia ; Microbial Interactions/*physiology ; Microbiota/*physiology ; Mouth/microbiology ; Phylogeny ; Plants/microbiology ; Ruminants/microbiology ; Soil Microbiology ; Symbiosis ; Viruses ; }, abstract = {Recent findings have shaken our picture of the biology of the archaea and revealed novel traits beyond archaeal extremophily and supposed 'primitiveness'. The archaea constitute a considerable fraction of the Earth's ecosystems, and their potential to shape their surroundings by a profound interaction with their biotic and abiotic environment has been recognized. Moreover, archaea have been identified as a substantial component, or even as keystone species, in complex microbiomes - in the environment or accompanying a holobiont. Species of the Euryarchaeota (methanogens, halophiles) and Thaumarchaeota, in particular, have the capacity to coexist in plant, animal, and human microbiomes, where syntrophy allows them to thrive under energy-deficiency stress. Due to methodological limitations, the archaeome remains mysterious, and many questions with respect to potential pathogenicity, function, and structural interactions with their host and other microorganisms remain.}, } @article {pmid28823759, year = {2018}, author = {Tsai, KN and Kuo, CF and Ou, JJ}, title = {Mechanisms of Hepatitis B Virus Persistence.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {33-42}, pmid = {28823759}, issn = {1878-4380}, support = {R01 AI129540/AI/NIAID NIH HHS/United States ; R01 CA177337/CA/NCI NIH HHS/United States ; R01 DK100257/DK/NIDDK NIH HHS/United States ; }, mesh = {Age Factors ; Child ; Gastrointestinal Microbiome/immunology ; Hepatitis B e Antigens ; Hepatitis B virus/genetics/*immunology/pathogenicity/*physiology ; Hepatitis B, Chronic/therapy ; Host-Pathogen Interactions/immunology ; Humans ; *Immunity, Innate ; Infectious Disease Transmission, Vertical ; Life Cycle Stages ; Maternal Inheritance/immunology ; Microbiota ; Viral Load ; }, abstract = {Hepatitis B virus (HBV) chronically infects 250 million people worldwide, resulting in nearly one million deaths annually. Studies in recent years have significantly improved our knowledge on the mechanisms of HBV persistence. HBV uses multiple pathways to harness host innate immunity to enhance its replication. It can also take advantage of the developing immune system and the not-yet-stabilized gut microbiota of young children to facilitate its persistence, and use maternal viral e antigen to educate immunity of the offspring to support its persistence after vertical transmission. The knowledge gained from these recent studies paves the way for the development of new therapies for the treatment of chronic HBV infection, which has so far been very challenging.}, } @article {pmid28823569, year = {2018}, author = {Hoppe-Seyler, K and Bossler, F and Braun, JA and Herrmann, AL and Hoppe-Seyler, F}, title = {The HPV E6/E7 Oncogenes: Key Factors for Viral Carcinogenesis and Therapeutic Targets.}, journal = {Trends in microbiology}, volume = {26}, number = {2}, pages = {158-168}, doi = {10.1016/j.tim.2017.07.007}, pmid = {28823569}, issn = {1878-4380}, mesh = {*Carcinogenesis ; Gene Expression Regulation, Neoplastic ; Gene Expression Regulation, Viral ; Host-Pathogen Interactions/genetics/physiology ; Humans ; Hypoxia ; Neoplasms/virology ; Oncogene Proteins/metabolism ; Oncogene Proteins, Viral/*metabolism ; Papillomaviridae/*pathogenicity ; Papillomavirus E7 Proteins/metabolism ; Repressor Proteins/metabolism ; TOR Serine-Threonine Kinases ; }, abstract = {Human papillomavirus (HPV)-induced cancers are expected to remain a major health problem worldwide for decades. The growth of HPV-positive cancer cells depends on the sustained expression of the viral E6 and E7 oncogenes which act in concert with still poorly defined cellular alterations. E6/E7 constitute attractive therapeutic targets since E6/E7 inhibition rapidly induces senescence in HPV-positive cancer cells. This cellular response is linked to the reconstitution of the antiproliferative p53 and pRb pathways, and to prosenescent mTOR signaling. Hypoxic HPV-positive cancer cells could be a major obstacle for treatment strategies targeting E6/E7 since they downregulate E6/E7 but evade senescence through hypoxia-induced mTOR impairment. Prospective E6/E7 inhibitors may therefore benefit from a combination with treatment strategies directed against hypoxic tumor cells.}, } @article {pmid28815925, year = {2018}, author = {Bejarano, MD and Jansson, R and Nilsson, C}, title = {The effects of hydropeaking on riverine plants: a review.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {658-673}, doi = {10.1111/brv.12362}, pmid = {28815925}, issn = {1469-185X}, abstract = {Hydropeaking refers to frequent, rapid and short-term fluctuations in water flow and water levels downstream and upstream of hydropower stations. Such fluctuations are becoming increasingly common worldwide and are known to have far-reaching effects on riverine vegetation. Novel hydrology caused by hydropeaking has no natural correspondence in freshwater systems, and hence few species have adaptations to all its aspects. Here, we review the literature on hydropeaking effects on riverine plants and define the state of the information on this human alteration of riverine ecosystems. We focus on riparian plants, but also draw on information from aquatic plant species, which exhibit a wide variety of adaptations to inundation and associated processes. Riparian plants face both physiological and physical constraints because of the shifts between submergence and drainage, and erosion of substrates. At the population level, hydropeaking may favour dispersal within, but not between, reservoirs, but may hamper germination, establishment, growth and reproduction. At the community level, strong filtering towards easily dispersed, flexible, flood-tolerant and amphibious plants is expected, although few species share these traits. Hence, most riparian plant species are expected to disappear or be pushed towards the upper boundaries of the regulated river margin. Future research should examine more closely global variation in hydropeaking effects, including other taxonomic groups of species and the diversity of hydropeaking regimes. There is also a need for studies focusing on identifying the boundaries within which hydropeaking could operate without impairing plant life.}, } @article {pmid28815473, year = {2018}, author = {Schwartz, AW}, title = {Publication of Abstracts and Full Papers from the International Conference on the Origin of Life, San Diego, 2017.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {3}, pages = {275}, doi = {10.1007/s11084-017-9549-y}, pmid = {28815473}, issn = {1573-0875}, mesh = {Biological Science Disciplines/*trends ; Humans ; *Origin of Life ; *Publishing ; Space Flight/*trends ; }, } @article {pmid28813201, year = {2018}, author = {Allen, RM and Metaxas, A and Snelgrove, PVR}, title = {Applying Movement Ecology to Marine Animals with Complex Life Cycles.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {19-42}, doi = {10.1146/annurev-marine-121916-063134}, pmid = {28813201}, issn = {1941-0611}, abstract = {Marine animals with complex life cycles may move passively or actively for fertilization, dispersal, predator avoidance, resource acquisition, and migration, and over scales from micrometers to thousands of kilometers. This diversity has catalyzed idiosyncratic and unfocused research, creating unsound paradigms regarding the role of movement in ecology and evolution. The emerging movement ecology paradigm offers a framework to consolidate movement research independent of taxon, life-history stage, scale, or discipline. This review applies the framework to movement among life-history stages in marine animals with complex life cycles to consolidate marine movement research and offer insights for scientists working in aquatic and terrestrial realms. Irrespective of data collection or simulation strategy, breaking each life-history stage down into the fundamental units of movement allows each unit to be studied independently or interactively with other units. Understanding these underlying mechanisms of movement within each life-history stage can then be used to construct lifetime movement paths. These paths can allow further investigation of the relative contributions and interdependencies of steps and phases across a lifetime and how these paths influence larger research topics, such as population-level movements.}, } @article {pmid28812194, year = {2018}, author = {Kitadai, N and Nishiuchi, K and Nishii, A and Fukushi, K}, title = {Amorphous Silica-Promoted Lysine Dimerization: a Thermodynamic Prediction.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {23-34}, doi = {10.1007/s11084-017-9548-z}, pmid = {28812194}, issn = {1573-0875}, mesh = {Adsorption ; *Dimerization ; Evolution, Chemical ; Lysine/*chemistry ; Silicon Dioxide/*chemistry ; Thermodynamics ; }, abstract = {It has long been suggested that mineral surfaces played a crucial role in the abiotic polymerization of amino acids that preceded the origin of life. Nevertheless, it remains unclear where the prebiotic process took place on the primitive Earth, because the amino acid-mineral interaction and its dependence on environmental conditions have yet to be understood adequately. Here we examined experimentally the adsorption of L-lysine (Lys) and its dimer (LysLys) on amorphous silica over a wide range of pH, ionic strength, adsorbate concentration, and the solid/water ratio, and determined the reaction stoichiometries and the equilibrium constants based on the extended triple-layer model (ETLM). The retrieved ETLM parameters were then used, in combination with the equilibrium constant for the peptide bond formation in bulk water, to calculate the Lys-LysLys equilibrium in the presence of amorphous silica under various aqueous conditions. Results showed that the silica surface favors Lys dimerization, and the influence varies greatly with changing environmental parameters. At slightly alkaline pH (pH 9) in the presence of a dilute NaCl (1 mM), the thermodynamically attainable LysLys from 0.1 mM Lys reached a concentration around 50 times larger than that calculated without silica. Because of the versatility of the ETLM, which has been applied to describe a wide variety of biomolecule-mineral interactions, future experiments with the reported methodology are expected to provide a significant constraint on the plausible geological settings for the condensation of monomers to polymers, and the subsequent chemical evolution of life.}, } @article {pmid28811217, year = {2018}, author = {Baghdadi, MB and Tajbakhsh, S}, title = {Regulation and phylogeny of skeletal muscle regeneration.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {200-209}, doi = {10.1016/j.ydbio.2017.07.026}, pmid = {28811217}, issn = {1095-564X}, mesh = {Animals ; Disease Models, Animal ; Gene Expression Regulation ; Gene Regulatory Networks ; Humans ; Invertebrates/physiology ; Macrophages/physiology ; Mice ; MicroRNAs/genetics ; Muscle, Skeletal/embryology/injuries/*physiology ; Myoblasts, Skeletal/physiology ; Neovascularization, Physiologic ; RNA, Long Noncoding/genetics ; Regeneration/*physiology ; Satellite Cells, Skeletal Muscle/physiology ; Signal Transduction ; Species Specificity ; Stem Cell Transplantation ; Stem Cells/physiology ; Stromal Cells/physiology ; Vertebrates/physiology ; }, abstract = {One of the most fascinating questions in regenerative biology is why some animals can regenerate injured structures while others cannot. Skeletal muscle has a remarkable capacity to regenerate even after repeated traumas, yet limited information is available on muscle repair mechanisms and how they have evolved. For decades, the main focus in the study of muscle regeneration was on muscle stem cells, however, their interaction with their progeny and stromal cells is only starting to emerge, and this is crucial for successful repair and re-establishment of homeostasis after injury. In addition, numerous murine injury models are used to investigate the regeneration process, and some can lead to discrepancies in observed phenotypes. This review addresses these issues and provides an overview of some of the main regulatory cellular and molecular players involved in skeletal muscle repair.}, } @article {pmid28803698, year = {2018}, author = {Hallin, S and Philippot, L and Löffler, FE and Sanford, RA and Jones, CM}, title = {Genomics and Ecology of Novel N2O-Reducing Microorganisms.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {43-55}, doi = {10.1016/j.tim.2017.07.003}, pmid = {28803698}, issn = {1878-4380}, mesh = {Archaea/classification/genetics/*metabolism ; Bacteria/classification/genetics/*metabolism ; Biological Evolution ; Climate Change ; Denitrification ; *Ecology ; *Genomics ; Greenhouse Gases ; Nitrogen/metabolism ; Nitrogen Cycle ; Nitrous Oxide/*metabolism ; Phylogeny ; Soil Microbiology ; }, abstract = {Microorganisms with the capacity to reduce the greenhouse gas nitrous oxide (N2O) to harmless dinitrogen gas are receiving increased attention due to increasing N2O emissions (and our need to mitigate climate change) and to recent discoveries of novel N2O-reducing bacteria and archaea. The diversity of denitrifying and nondenitrifying microorganisms with capacity for N2O reduction was recently shown to be greater than previously expected. A formerly overlooked group (clade II) in the environment include a large fraction of nondenitrifying N2O reducers, which could be N2O sinks without major contribution to N2O formation. We review the recent advances about fundamental understanding of the genomics, physiology, and ecology of N2O reducers and the importance of these findings for curbing N2O emissions.}, } @article {pmid28802725, year = {2018}, author = {Burgess, ML and McFarlin, SC and Mudakikwa, A and Cranfield, MR and Ruff, CB}, title = {Body mass estimation in hominoids: Age and locomotor effects.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {36-46}, doi = {10.1016/j.jhevol.2017.07.004}, pmid = {28802725}, issn = {1095-8606}, abstract = {While there are a number of methods available for estimation of body mass in adult nonhuman primates, very few are available for juveniles, despite the potential utility of such estimations in both analyses of fossils and in museum collection based research. Furthermore, because of possible scaling differences, adult based body mass estimation equations may not be appropriate for non-adults. In this study, we present new body mass estimation equations for both adult and immature nonhuman hominoids based on joint and metaphyseal dimensions. Articular breadths of the proximal and distal femur, distal humerus and tibial plateau, and metaphyseal breadths of the distal femur and humerus were collected on a reference sample of 159 wild Pan, Gorilla, Pongo, Hylobates, and Symphalangus specimens of known body mass from museum and research collections. Scaling of dimensions with body weight was assessed in both the adult and the ontogenetic sample at several taxonomic levels using reduced major axis regression, followed by regression of each dimension against body mass to generate body mass estimation equations. Joint dimensions were found to be good predictors of body mass in both adult and immature hominoids, with percent prediction errors of 10-20%. However, subtle scaling differences between taxa impacted body mass estimation, suggesting that phylogeny and locomotor effects should be considered when selecting reference samples. Unlike patterns of joint growth in humans, there was little conclusive evidence for consistently larger joints relative to body mass in the non-adult sample. Metaphyseal breadths were strong predictors of body mass and, with some exceptions, gave more precise body mass estimates for non-adults than epiphyseal breadths.}, } @article {pmid28802724, year = {2018}, author = {Cowgill, L}, title = {Juvenile body mass estimation: A methodological evaluation.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {78-84}, doi = {10.1016/j.jhevol.2017.07.007}, pmid = {28802724}, issn = {1095-8606}, abstract = {Two attempts have been made to develop body mass prediction formulae specifically for immature remains: Ruff (Ruff, C.C., 2007, Body size prediction from juvenile skeletal remains. American Journal Physical Anthropology 133, 698-716) and Robbins et al. (Robbins, G., Sciulli, P.W., Blatt, S.H., 2010. Estimating body mass in subadult human skeletons. American Journal Physical Anthropology 143, 146-150). While both were developed from the same reference population, they differ in their independent variable selection: Ruff (2008) used measures of metaphyseal and articular surface size to predict body mass in immature remains, whereas Robbins et al. (2010) relied on cross-sectional properties. Both methods perform well on independent testing samples; however, differences between the two methods exist in the predicted values. This research evaluates the differences in the body mass estimates from these two methods in seven geographically diverse skeletal samples under the age of 18 (n = 461). The purpose of this analysis is not to assess which method performs with greater accuracy or precision; instead, differences between the two methods are used as a heuristic device to focus attention on the unique challenges affecting the prediction of immature body mass estimates in particular. The two methods differ by population only in some cases, which may be a reflection of activity variation or nutritional status. In addition, cross-sectional properties almost always produce higher estimates than metaphyseal surface size across all age categories. This highlights the difficulty in teasing apart information related to body mass from that relevant to loading, particularly when the original reference population is urban/industrial.}, } @article {pmid28802723, year = {2018}, author = {de la Torre, I and Wehr, K}, title = {Site formation processes of the early Acheulean assemblage at EF-HR (Olduvai Gorge, Tanzania).}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {298-328}, doi = {10.1016/j.jhevol.2017.07.002}, pmid = {28802723}, issn = {1095-8606}, abstract = {This paper investigates the formation history of the early Acheulean site of EF-HR (Olduvai Gorge, Tanzania). Our study focuses on the main site (T2-Main Trench) and adjacent trenches (T12 and T9), which constitute the bulk of the archaeological assemblage recently excavated in the EF-HR area (de la Torre et al., 2018a). Site formation processes are investigated through taphonomic proxies and spatial analysis, and consider artifact features, orientation patterns, and topographic data retrieved during archaeological excavation. This enables an assessment of the impact of natural agents on the assemblage and a discussion of the relevance of water disturbance in shaping the structure of the EF-HR archaeological record. Our results indicate that fluvial action over the assemblage was significant, although it is likely that EF-HR still preserves areas marginally affected by water sorting and rearrangement. In summary, by applying a novel approach that combines a systematic analysis of artifact attributes with GIS spatial analysis of archaeological remains and topographic features, our study aims to provide a fresh look at the interaction of human and natural agents in the formation of Early Stone Age assemblages at Olduvai Gorge.}, } @article {pmid28799256, year = {2018}, author = {Chenuil, A and Saucède, T and Hemery, LG and Eléaume, M and Féral, JP and Améziane, N and David, B and Lecointre, G and Havermans, C}, title = {Understanding processes at the origin of species flocks with a focus on the marine Antarctic fauna.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {481-504}, doi = {10.1111/brv.12354}, pmid = {28799256}, issn = {1469-185X}, abstract = {Species flocks (SFs) fascinate evolutionary biologists who wonder whether such striking diversification can be driven by normal evolutionary processes. Multiple definitions of SFs have hindered the study of their origins. Previous studies identified a monophyletic taxon as a SF if it displays high speciosity in an area in which it is endemic (criterion 1), high ecological diversity among species (criterion 2), and if it dominates the habitat in terms of biomass (criterion 3); we used these criteria in our analyses. Our starting hypothesis is that normal evolutionary processes may provide a sufficient explanation for most SFs. We thus clearly separate each criterion and identify which biological (intrinsic) and environmental (extrinsic) traits are most favourable to their realization. The first part focuses on evolutionary processes. We highlight that some popular putative causes of SFs, such as key innovations or ecological speciation, are neither necessary nor sufficient to fulfill some or all of the three criteria. Initial differentiation mechanisms are diverse and difficult to identify a posteriori because a primary differentiation of one type (genetic, ecological or geographical) often promotes other types of differentiation. Furthermore, the criteria are not independent: positive feedbacks between speciosity and ecological diversity among species are expected whatever the initial cause of differentiation, and ecological diversity should enhance habitat dominance at the clade level. We then identify intrinsic and extrinsic factors that favour each criterion. Low dispersal emerges as a convincing driver of speciosity. Except for a genomic architecture favouring ecological speciation, for which assessment is difficult, high effective population sizes are the single intrinsic factor that directly enhances speciosity, ecological diversity and habitat dominance. No extrinsic factor appeared to enhance all criteria simultaneously but a combination of factors (insularity, fragmentation and environmental stability) may favour the three criteria, although the effect is indirect for habitat dominance. We then apply this analytical framework to Antarctic marine environments by analysing data from 18 speciose clades belonging to echinoderms (five unrelated clades), notothenioid fishes (five clades) and peracarid crustaceans (eight clades). Antarctic shelf environments and history appear favourable to endemicity and speciosity, but not to ecological specialization. Two main patterns are distinguished among taxa. (i) In echinoderms, many brooding, species-rich and endemic clades are reported, but without remarkable ecological diversity or habitat dominance. In these taxa, loss of the larval stage is probably a consequence of past Antarctic environmental factors, and brooding is suggested to be responsible for enhanced allopatric speciation (via dispersal limitation). (ii) In notothenioids and peracarids, many clades fulfill all three SF criteria. This could result from unusual features in fish and crustaceans: chromosome instability and key innovations (antifreeze proteins) in notothenioids, ecological opportunity in peracarids, and a genomic architecture favouring ecological speciation in both groups. Therefore, the data do not support our starting point that normal evolutionary factors or processes drive SFs because in these two groups uncommon intrinsic features or ecological opportunity provide the best explanation. The utility of the three-criterion SF concept is therefore questioned and guidelines are given for future studies.}, } @article {pmid28797516, year = {2018}, author = {Pante, MC and Njau, JK and Hensley-Marschand, B and Keevil, TL and Martín-Ramos, C and Peters, RF and de la Torre, I}, title = {The carnivorous feeding behavior of early Homo at HWK EE, Bed II, Olduvai Gorge, Tanzania.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {215-235}, doi = {10.1016/j.jhevol.2017.06.005}, pmid = {28797516}, issn = {1095-8606}, abstract = {The regular consumption of large mammal carcasses, as evidenced by butchery marks on fossils recovered from Early Stone Age archaeological sites, roughly coincides with the appearance of Homo habilis. However, the significance of this niche expansion cannot be appreciated without an understanding of hominin feeding behavior and their ecological interactions with mammalian carnivores. The Olduvai Geochronology and Archaeology Project (OGAP) has recovered a large and well-preserved fossil assemblage from the HWK EE site, which was deposited just prior to the first appearance of Acheulean technology at Olduvai Gorge and likely represents one of the last H. habilis sites at Olduvai. This taphonomic analysis of the larger mammal fossil assemblage excavated from HWK EE shows evidence of multiple occupations over a long period of time, suggesting the site offered resources that were attractive to hominins. There was a water source indicated by the presence of fish, crocodiles, and hippos, and there was possible tree cover in an otherwise open habitat. The site preserves several stratigraphic intervals with large fossil and artifact assemblages within two of these intervals. Feeding traces on bone surfaces suggest hominins at the site obtained substantial amounts of flesh and marrow, particularly from smaller size group 1-2 carcasses, and exploited a wide range of taxa, including megafauna. A strong carnivore signal suggests hominins scavenged much of their animal foods during the two main stratigraphic intervals. In the later interval, lower carnivore tooth mark and hammerstone percussion mark frequencies, in addition to high epiphyseal to shaft fragment ratios, suggest hominins and carnivores did not fully exploit bone marrow and grease, which may have been acquired from nutritionally-stressed animals that died during a dry period at Olduvai. The diversity of fauna that preserve evidence of butchery suggests that the HWK EE hominins were opportunistic in their acquisition of carcass foods.}, } @article {pmid28796571, year = {2018}, author = {Woodson, CB}, title = {The Fate and Impact of Internal Waves in Nearshore Ecosystems.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {421-441}, doi = {10.1146/annurev-marine-121916-063619}, pmid = {28796571}, issn = {1941-0611}, abstract = {Internal waves are widespread features of global oceans that play critical roles in mixing and thermohaline circulation. Similarly to surface waves, internal waves can travel long distances, ultimately breaking along continental margins. These breaking waves can transport deep ocean water and associated constituents (nutrients, larvae, and acidic low-oxygen waters) onto the shelf and locally enhance turbulence and mixing, with important effects on nearshore ecosystems. We are only beginning to understand the role internal waves play in shaping nearshore ecosystems. Here, I review the physics of internal waves in shallow waters and identify two commonalities among internal waves in the nearshore: exposure to deep offshore waters and enhanced turbulence and mixing. I relate these phenomena to important ecosystem processes ranging from extreme events to fertilization success to draw general conclusions about the influence of internal waves on ecosystems and the effects of internal waves in a changing climate.}, } @article {pmid28795526, year = {2018}, author = {Zhu, S and Yao, F and Qiu, H and Zhang, G and Xu, H and Xu, J}, title = {Coupling factors and exosomal packaging microRNAs involved in the regulation of bone remodelling.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {469-480}, doi = {10.1111/brv.12353}, pmid = {28795526}, issn = {1469-185X}, abstract = {Bone remodelling is a continuous process by which bone resorption by osteoclasts is followed by bone formation by osteoblasts to maintain skeletal homeostasis. These two forces must be tightly coordinated not only quantitatively, but also in time and space, and its malfunction leads to diseases such as osteoporosis. Recent research focusing on the cross-talk and coupling mechanisms associated with the sequential recruitment of osteoblasts to areas where osteoclasts have removed bone matrix have identified a number of osteogenic factors produced by the osteoclasts themselves. Osteoclast-derived factors and exosomal-containing microRNA (miRNA) can either enhance or inhibit osteoblast differentiation through paracrine and juxtacrine mechanisms, and therefore may have a central coupling role in bone formation. Entwined with angiocrine factors released by vessel-specific endothelial cells and perivascular cells or pericytes, these factors play a critical role in angiogenesis-osteogenesis coupling essential in bone remodelling.}, } @article {pmid28795474, year = {2018}, author = {Windsor, FM and Ormerod, SJ and Tyler, CR}, title = {Endocrine disruption in aquatic systems: up-scaling research to address ecological consequences.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {626-641}, doi = {10.1111/brv.12360}, pmid = {28795474}, issn = {1469-185X}, abstract = {Endocrine-disrupting chemicals (EDCs) can alter biological function in organisms at environmentally relevant concentrations and are a significant threat to aquatic biodiversity, but there is little understanding of exposure consequences for populations, communities and ecosystems. The pervasive nature of EDCs within aquatic environments and their multiple sub-lethal effects make assessments of their impact especially important but also highly challenging. Herein, we review the data on EDC effects in aquatic systems focusing on studies assessing populations and ecosystems, and including how biotic and abiotic processes may affect, and be affected by, responses to EDCs. Recent research indicates a significant influence of behavioural responses (e.g. enhancing feeding rates), transgenerational effects and trophic cascades in the ecological consequences of EDC exposure. In addition, interactions between EDCs and other chemical, physical and biological factors generate uncertainty in our understanding of the ecological effects of EDCs within aquatic ecosystems. We illustrate how effect thresholds for EDCs generated from individual-based experimental bioassays of the types commonly applied using chemical test guidelines [e.g. Organisation for Economic Co-operation and Development (OECD)] may not necessarily reflect the hazards associated with endocrine disruption. We argue that improved risk assessment for EDCs in aquatic ecosystems urgently requires more ecologically oriented research as well as field-based assessments at population-, community- and food-web levels.}, } @article {pmid28793810, year = {2018}, author = {Purkis, SJ}, title = {Remote Sensing Tropical Coral Reefs: The View from Above.}, journal = {Annual review of marine science}, volume = {10}, number = {}, pages = {149-168}, doi = {10.1146/annurev-marine-121916-063249}, pmid = {28793810}, issn = {1941-0611}, abstract = {Carbonate precipitation has been a common life strategy for marine organisms for 3.7 billion years, as, therefore, has their construction of reefs. As favored by modern corals, reef-forming organisms have typically adopted a niche in warm, shallow, well-lit, tropical marine waters, where they are capable of building vast carbonate edifices. Because fossil reefs form water aquifers and hydrocarbon reservoirs, considerable effort has been dedicated to understanding their anatomy and morphology. Remote sensing has a particular role to play here. Interpretation of satellite images has done much to reveal the grand spatial and temporal tapestry of tropical reefs. Comparative sedimentology, whereby modern environments are contrasted with the rock record to improve interpretation, has been particularly transformed by observations made from orbit. Satellite mapping has also become a keystone technology to quantify the coral reef crisis-it can be deployed not only directly to quantify the distribution of coral communities, but also indirectly to establish a climatology for their physical environment. This article reviews the application of remote sensing to tropical coralgal reefs in order to communicate how this fast-growing technology might be central to addressing the coral reef crisis and to look ahead at future developments in the science.}, } @article {pmid28784352, year = {2018}, author = {Preston, S and Gasser, RB}, title = {Working towards New Drugs against Parasitic Worms in a Public-Development Partnership.}, journal = {Trends in parasitology}, volume = {34}, number = {1}, pages = {4-6}, doi = {10.1016/j.pt.2017.07.005}, pmid = {28784352}, issn = {1471-5007}, mesh = {Animals ; Anthelmintics/economics/*therapeutic use ; Drug Discovery/*economics/*trends ; Helminthiasis/*drug therapy ; Humans ; *Public-Private Sector Partnerships ; }, abstract = {There is a clear need to develop new and inexpensive drugs to alleviate diseases caused by parasitic worms in animals and humans worldwide. In this article we discuss the roles and advantages of working in public-private partnerships (PPPs) - among academia, industry, and philanthropy - to enable anthelmintic drug discovery.}, } @article {pmid28780964, year = {2018}, author = {de la Torre, I and Albert, RM and Macphail, R and McHenry, LJ and Pante, MC and Rodríguez-Cintas, Á and Stanistreet, IG and Stollhofen, H}, title = {The contexts and early Acheulean archaeology of the EF-HR paleo-landscape (Olduvai Gorge, Tanzania).}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {274-297}, doi = {10.1016/j.jhevol.2017.06.012}, pmid = {28780964}, issn = {1095-8606}, abstract = {Renewed fieldwork at the early Acheulean site of EF-HR (Olduvai Gorge, Tanzania) has included detailed stratigraphic studies of the sequence, extended excavations in the main site, and has placed eleven additional trenches within an area of nearly 1 km2, to sample the same stratigraphic interval as in the main trench across the broader paleo-landscape. Our new stratigraphic work suggests that EF-HR is positioned higher in the Bed II sequence than previously proposed, which has implications for the age of the site and its stratigraphic correlation to other Olduvai Middle Bed II sites. Geological research shows that the main EF-HR site was situated at the deepest part of an incised valley formed through river erosion. Archaeological excavations at the main site and nearby trenches have unearthed a large new assemblage, with more than 3000 fossils and artefacts, including a hundred handaxes in stratigraphic position. In addition, our test-trenching approach has detected conspicuous differences in the density of artefacts across the landscape, with a large cluster of archaeological material in and around the main trench, and less intense human activity at the same level in the more distant satellite trenches. All of these aspects are discussed in this paper in the light of site formation processes, behavioral contexts, and their implications for our understanding of the early Acheulean at Olduvai Gorge.}, } @article {pmid28778874, year = {2018}, author = {Yap, AS and Duszyc, K and Viasnoff, V}, title = {Mechanosensing and Mechanotransduction at Cell-Cell Junctions.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a028761}, pmid = {28778874}, issn = {1943-0264}, abstract = {Cell adhesion systems are defined by their ability to resist detachment force. Our understanding of the biology of cell-cell adhesions has recently been transformed by the realization that many of the forces that act on those adhesions are generated by the cells that they couple together; and that force at adhesive junctions can be sensed to regulate cell behavior. Here, we consider the mechanisms responsible for applying force to cell-cell junctions and the mechanosensory pathways that detect those forces. We focus on cadherins, as these are the best-studied examples to date, but it is likely that similar principles will apply to other molecular systems that can engage with force-generators within cells and physically couple those cells together.}, } @article {pmid28778873, year = {2018}, author = {Kim, MO and Takada, LT and Wong, K and Forner, SA and Geschwind, MD}, title = {Genetic PrP Prion Diseases.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a033134}, pmid = {28778873}, issn = {1943-0264}, abstract = {Genetic prion diseases (gPrDs) caused by mutations in the prion protein gene (PRNP) have been classified as genetic Creutzfeldt-Jakob disease, Gerstmann-Sträussler-Scheinker disease, or fatal familial insomnia. Mutations in PRNP can be missense, nonsense, and/or octapeptide repeat insertions or, possibly, deletions. These mutations can produce diverse clinical features. They may also show varying ancillary testing results and neuropathological findings. Although the majority of gPrDs have a rapid progression with a short survival time of a few months, many also present as ataxic or parkinsonian disorders, which have a slower decline over a few to several years. A few very rare mutations manifest as neuropsychiatric disorders, with systemic symptoms that include gastrointestinal disorders and neuropathy; these forms can progress over years to decades. In this review, we classify gPrDs as rapid, slow, or mixed types based on their typical rate of progression and duration, and we review the broad spectrum of phenotypes manifested by these diseases.}, } @article {pmid28778872, year = {2018}, author = {Delmar, M and Laird, DW and Naus, CC and Nielsen, MS and Verselis, VK and White, TW}, title = {Connexins and Disease.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {9}, pages = {}, doi = {10.1101/cshperspect.a029348}, pmid = {28778872}, issn = {1943-0264}, support = {R01 EY013163/EY/NEI NIH HHS/United States ; R01 EY026911/EY/NEI NIH HHS/United States ; }, abstract = {Inherited or acquired alterations in the structure and function of connexin proteins have long been associated with disease. In the present work, we review current knowledge on the role of connexins in diseases associated with the heart, nervous system, cochlea, and skin, as well as cancer and pleiotropic syndromes such as oculodentodigital dysplasia (ODDD). Although incomplete by virtue of space and the extent of the topic, this review emphasizes the fact that connexin function is not only associated with gap junction channel formation. As such, both canonical and noncanonical functions of connexins are fundamental components in the pathophysiology of multiple connexin related disorders, many of them highly debilitating and life threatening. Improved understanding of connexin biology has the potential to advance our understanding of mechanisms, diagnosis, and treatment of disease.}, } @article {pmid28778871, year = {2018}, author = {Galdiero, MR and Marone, G and Mantovani, A}, title = {Cancer Inflammation and Cytokines.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a028662}, pmid = {28778871}, issn = {1943-0264}, abstract = {Chronic inflammation is a well-recognized tumor-enabling capability, which allows nascent tumors to escape immunosurveillance. A number of soluble and cellular inflammatory mediators take part in the various phases of cancer initiation and progression, giving rise to a fatal conspiracy, which is difficult to efficiently overcome. Tumor-associated macrophages (TAMs) are pivotal players of the tumor microenvironment and, because of their characteristic plasticity, can acquire a number of distinct phenotypes and contribute in different ways to the various phases of cancerogenesis. Tumor-associated neutrophils (TANs) are also emerging as important components of the tumor microenvironment, given their unexpected heterogeneity and plasticity. TAMs and TANs are both integrated in cancer-related inflammation and an ever better understanding of their functions can be useful to tailor the use of anticancer therapeutic approaches and patient follow-up.}, } @article {pmid28778870, year = {2018}, author = {Tanaka, T and Narazaki, M and Kishimoto, T}, title = {Interleukin (IL-6) Immunotherapy.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {8}, pages = {}, doi = {10.1101/cshperspect.a028456}, pmid = {28778870}, issn = {1943-0264}, abstract = {Interleukin 6 (IL-6) is a prototypical cytokine for maintaining homeostasis. When homeostasis is disrupted by infections or tissue injuries, IL-6 is produced immediately and contributes to host defense against such emergent stress through activation of acute-phase and immune responses. However, dysregulated excessive and persistent synthesis of IL-6 has a pathological effect on, respectively, acute systemic inflammatory response syndrome and chronic immune-mediated diseases. The IL-6 inhibitor, tocilizumab, a humanized anti-IL-6 receptor antibody, is currently being used for the treatment of rheumatoid arthritis, juvenile idiopathic arthritis, and Castleman disease. Lines of recent evidence strongly suggest IL-6 blockade can provide broader therapeutic strategy for various diseases included in acute systemic and chronic inflammatory diseases.}, } @article {pmid28778869, year = {2018}, author = {Green, CB}, title = {Circadian Posttranscriptional Regulatory Mechanisms in Mammals.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a030692}, pmid = {28778869}, issn = {1943-0264}, abstract = {The circadian clock drives rhythms in the levels of thousands of proteins in the mammalian cell, arising in part from rhythmic transcriptional regulation of the genes that encode them. However, recent evidence has shown that posttranscriptional processes also play a major role in generating the rhythmic protein makeup and ultimately the rhythmic physiology of the cell. Regulation of steps throughout the life of the messenger RNA (mRNA), ranging from initial mRNA processing and export from the nucleus to extensive control of translation and degradation in the cytosol have been shown to be important for producing the final rhythms in protein levels critical for proper circadian rhythmicity. These findings will be reviewed here.}, } @article {pmid28778868, year = {2018}, author = {Jontes, JD}, title = {The Cadherin Superfamily in Neural Circuit Assembly.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, pmid = {28778868}, issn = {1943-0264}, support = {R01 EY027003/EY/NEI NIH HHS/United States ; }, abstract = {The cadherin superfamily comprises a large, diverse collection of cell surface receptors that are expressed in the nervous system throughout development and have been shown to be essential for the proper assembly of the vertebrate nervous system. As our knowledge of each family member has grown, it has become increasingly clear that the functions of various cadherin subfamilies are intertwined: they can be present in the same protein complexes, impinge on the same developmental processes, and influence the same signaling pathways. This interconnectedness may illustrate a central way in which core developmental events are controlled to bring about the robust and precise assembly of neural circuitry.}, } @article {pmid28778867, year = {2018}, author = {Milev, NB and Rhee, SG and Reddy, AB}, title = {Cellular Timekeeping: It's Redox o'Clock.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a027698}, pmid = {28778867}, issn = {1943-0264}, abstract = {Mounting evidence in recent years supports the extensive interaction between the circadian and redox systems. The existence of such a relationship is not surprising because most organisms, be they diurnal or nocturnal, display daily oscillations in energy intake, locomotor activity, and exposure to exogenous and internally generated oxidants. The transcriptional clock controls the levels of many antioxidant proteins and redox-active cofactors, and, conversely, the cellular redox poise has been shown to feed back to the transcriptional oscillator via redox-sensitive transcription factors and enzymes. However, the circadian cycles in the S-sulfinylation of the peroxiredoxin (PRDX) proteins constituted the first example of an autonomous circadian redox oscillation, which occurred independently of the transcriptional clock. Importantly, the high phylogenetic conservation of these rhythms suggests that they might predate the evolution of the transcriptional oscillator, and therefore could be a part of a primordial circadian redox/metabolic oscillator. This discovery forced the reappraisal of the dogmatic transcription-centered view of the clockwork and opened a new avenue of research. Indeed, the investigation into the links between the circadian and redox systems is still in its infancy, and many important questions remain to be addressed.}, } @article {pmid28776950, year = {2018}, author = {Saastamoinen, M and Bocedi, G and Cote, J and Legrand, D and Guillaume, F and Wheat, CW and Fronhofer, EA and Garcia, C and Henry, R and Husby, A and Baguette, M and Bonte, D and Coulon, A and Kokko, H and Matthysen, E and Niitepõld, K and Nonaka, E and Stevens, VM and Travis, JMJ and Donohue, K and Bullock, JM and Del Mar Delgado, M}, title = {Genetics of dispersal.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {574-599}, pmid = {28776950}, issn = {1469-185X}, abstract = {Dispersal is a process of central importance for the ecological and evolutionary dynamics of populations and communities, because of its diverse consequences for gene flow and demography. It is subject to evolutionary change, which begs the question, what is the genetic basis of this potentially complex trait? To address this question, we (i) review the empirical literature on the genetic basis of dispersal, (ii) explore how theoretical investigations of the evolution of dispersal have represented the genetics of dispersal, and (iii) discuss how the genetic basis of dispersal influences theoretical predictions of the evolution of dispersal and potential consequences. Dispersal has a detectable genetic basis in many organisms, from bacteria to plants and animals. Generally, there is evidence for significant genetic variation for dispersal or dispersal-related phenotypes or evidence for the micro-evolution of dispersal in natural populations. Dispersal is typically the outcome of several interacting traits, and this complexity is reflected in its genetic architecture: while some genes of moderate to large effect can influence certain aspects of dispersal, dispersal traits are typically polygenic. Correlations among dispersal traits as well as between dispersal traits and other traits under selection are common, and the genetic basis of dispersal can be highly environment-dependent. By contrast, models have historically considered a highly simplified genetic architecture of dispersal. It is only recently that models have started to consider multiple loci influencing dispersal, as well as non-additive effects such as dominance and epistasis, showing that the genetic basis of dispersal can influence evolutionary rates and outcomes, especially under non-equilibrium conditions. For example, the number of loci controlling dispersal can influence projected rates of dispersal evolution during range shifts and corresponding demographic impacts. Incorporating more realism in the genetic architecture of dispersal is thus necessary to enable models to move beyond the purely theoretical towards making more useful predictions of evolutionary and ecological dynamics under current and future environmental conditions. To inform these advances, empirical studies need to answer outstanding questions concerning whether specific genes underlie dispersal variation, the genetic architecture of context-dependent dispersal phenotypes and behaviours, and correlations among dispersal and other traits.}, } @article {pmid28774726, year = {2018}, author = {Almazan, EMP and Lesko, SL and Markey, MP and Rouhana, L}, title = {Girardia dorotocephala transcriptome sequence, assembly, and validation through characterization of piwi homologs and stem cell progeny markers.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {433-447}, pmid = {28774726}, issn = {1095-564X}, support = {R15 HD082754/HD/NICHD NIH HHS/United States ; R25 GM090122/GM/NIGMS NIH HHS/United States ; R25 HL103168/HL/NHLBI NIH HHS/United States ; }, mesh = {Animals ; Argonaute Proteins/*genetics/physiology ; Biomarkers ; Cloning, Organism ; *Genes, Helminth ; Helminth Proteins/biosynthesis/*genetics ; Homeostasis/genetics ; Multigene Family ; Planarians/*genetics ; RNA Interference ; RNA, Double-Stranded/administration & dosage/genetics ; RNA, Messenger/biosynthesis/genetics ; Regeneration/genetics ; Reproduction, Asexual ; Sequence Analysis, RNA ; Stem Cells/*cytology ; *Transcriptome ; }, abstract = {Planarian flatworms are popular models for the study of regeneration and stem cell biology in vivo. Technical advances and increased availability of genetic information have fueled the discovery of molecules responsible for stem cell pluripotency and regeneration in flatworms. Unfortunately, most of the planarian research performed worldwide utilizes species that are not natural habitants of North America, which limits their availability to newcomer laboratories and impedes their distribution for educational activities. In order to circumvent these limitations and increase the genetic information available for comparative studies, we sequenced the transcriptome of Girardia dorotocephala, a planarian species pandemic and commercially available in North America. A total of 254,802,670 paired sequence reads were obtained from RNA extracted from intact individuals, regenerating fragments, as well as freshly excised auricles of a clonal line of G. dorotocephala (MA-C2), and used for de novo assembly of its transcriptome. The resulting transcriptome draft was validated through functional analysis of genetic markers of stem cells and their progeny in G. dorotocephala. Akin to orthologs in other planarian species, G. dorotocephala Piwi1 (GdPiwi1) was found to be a robust marker of the planarian stem cell population and GdPiwi2 an essential component for stem cell-driven regeneration. Identification of G. dorotocephala homologs of the early stem cell descendent marker PROG-1 revealed a family of lysine-rich proteins expressed during epithelial cell differentiation. Sequences from the MA-C2 transcriptome were found to be 98-99% identical to nucleotide sequences from G. dorotocephala populations with different chromosomal number, demonstrating strong conservation regardless of karyotype evolution. Altogether, this work establishes G. dorotocephala as a viable and accessible option for analysis of gene function in North America.}, } @article {pmid28772023, year = {2018}, author = {Dyksma, S and Pjevac, P and Ovanesov, K and Mussmann, M}, title = {Evidence for H2 consumption by uncultured Desulfobacterales in coastal sediments.}, journal = {Environmental microbiology}, volume = {20}, number = {2}, pages = {450-461}, doi = {10.1111/1462-2920.13880}, pmid = {28772023}, issn = {1462-2920}, abstract = {Molecular hydrogen (H2) is the key intermediate in the anaerobic degradation of organic matter. Its removal by H2 -oxidizing microorganisms is essential to keep anaerobic degradation energetically favourable. Sulfate-reducing microorganisms (SRM) are known as the main H2 scavengers in anoxic marine sediments. Although the community of marine SRM has been extensively studied, those consuming H2 in situ are completely unknown. We combined metagenomics, PCR-based clone libraries, single-amplified genomes (SAGs) and metatranscriptomics to identify potentially H2 -consuming SRM in anoxic coastal sediments. The vast majority of SRM-related H2 ase sequences were assigned to group 1b and 1c [NiFe]-H2 ases of the deltaproteobacterial order Desulfobacterales. Surprisingly, the same sequence types were similarly highly expressed in spring and summer, suggesting that these are stable and integral members of the H2 -consuming community. Notably, one sequence cluster from the SRM group 1 consistently accounted for around half of all [NiFe]-H2 ase transcripts. Using SAGs, we could link this cluster with the 16S rRNA genes of the uncultured Sva0081-group of the family Desulfobacteraceae. Sequencing of 16S rRNA gene amplicons and H2 ase gene libraries suggested consistently high in situ abundance of the Sva0081 group also in other marine sediments. Together with other Desulfobacterales these likely are important H2 -scavengers in marine sediments.}, } @article {pmid28766908, year = {2018}, author = {Kissling, WD and Ahumada, JA and Bowser, A and Fernandez, M and Fernández, N and García, EA and Guralnick, RP and Isaac, NJB and Kelling, S and Los, W and McRae, L and Mihoub, JB and Obst, M and Santamaria, M and Skidmore, AK and Williams, KJ and Agosti, D and Amariles, D and Arvanitidis, C and Bastin, L and De Leo, F and Egloff, W and Elith, J and Hobern, D and Martin, D and Pereira, HM and Pesole, G and Peterseil, J and Saarenmaa, H and Schigel, D and Schmeller, DS and Segata, N and Turak, E and Uhlir, PF and Wee, B and Hardisty, AR}, title = {Building essential biodiversity variables (EBVs) of species distribution and abundance at a global scale.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {600-625}, doi = {10.1111/brv.12359}, pmid = {28766908}, issn = {1469-185X}, abstract = {Much biodiversity data is collected worldwide, but it remains challenging to assemble the scattered knowledge for assessing biodiversity status and trends. The concept of Essential Biodiversity Variables (EBVs) was introduced to structure biodiversity monitoring globally, and to harmonize and standardize biodiversity data from disparate sources to capture a minimum set of critical variables required to study, report and manage biodiversity change. Here, we assess the challenges of a 'Big Data' approach to building global EBV data products across taxa and spatiotemporal scales, focusing on species distribution and abundance. The majority of currently available data on species distributions derives from incidentally reported observations or from surveys where presence-only or presence-absence data are sampled repeatedly with standardized protocols. Most abundance data come from opportunistic population counts or from population time series using standardized protocols (e.g. repeated surveys of the same population from single or multiple sites). Enormous complexity exists in integrating these heterogeneous, multi-source data sets across space, time, taxa and different sampling methods. Integration of such data into global EBV data products requires correcting biases introduced by imperfect detection and varying sampling effort, dealing with different spatial resolution and extents, harmonizing measurement units from different data sources or sampling methods, applying statistical tools and models for spatial inter- or extrapolation, and quantifying sources of uncertainty and errors in data and models. To support the development of EBVs by the Group on Earth Observations Biodiversity Observation Network (GEO BON), we identify 11 key workflow steps that will operationalize the process of building EBV data products within and across research infrastructures worldwide. These workflow steps take multiple sequential activities into account, including identification and aggregation of various raw data sources, data quality control, taxonomic name matching and statistical modelling of integrated data. We illustrate these steps with concrete examples from existing citizen science and professional monitoring projects, including eBird, the Tropical Ecology Assessment and Monitoring network, the Living Planet Index and the Baltic Sea zooplankton monitoring. The identified workflow steps are applicable to both terrestrial and aquatic systems and a broad range of spatial, temporal and taxonomic scales. They depend on clear, findable and accessible metadata, and we provide an overview of current data and metadata standards. Several challenges remain to be solved for building global EBV data products: (i) developing tools and models for combining heterogeneous, multi-source data sets and filling data gaps in geographic, temporal and taxonomic coverage, (ii) integrating emerging methods and technologies for data collection such as citizen science, sensor networks, DNA-based techniques and satellite remote sensing, (iii) solving major technical issues related to data product structure, data storage, execution of workflows and the production process/cycle as well as approaching technical interoperability among research infrastructures, (iv) allowing semantic interoperability by developing and adopting standards and tools for capturing consistent data and metadata, and (v) ensuring legal interoperability by endorsing open data or data that are free from restrictions on use, modification and sharing. Addressing these challenges is critical for biodiversity research and for assessing progress towards conservation policy targets and sustainable development goals.}, } @article {pmid28760345, year = {2018}, author = {König, D and Page, L and Chassot, B and Jaźwińska, A}, title = {Dynamics of actinotrichia regeneration in the adult zebrafish fin.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {416-432}, doi = {10.1016/j.ydbio.2017.07.024}, pmid = {28760345}, issn = {1095-564X}, mesh = {Animal Fins/*physiology/ultrastructure ; Animal Structures/metabolism/ultrastructure ; Animals ; Collagen/metabolism/ultrastructure ; Extracellular Matrix/metabolism ; Gene Expression Regulation ; Homeostasis ; Mesoderm ; Osteoblasts/metabolism ; Regeneration/*physiology ; Wound Healing/physiology ; Zebrafish/genetics/*physiology ; Zebrafish Proteins/biosynthesis/genetics/*physiology ; }, abstract = {The skeleton of adult zebrafish fins comprises lepidotrichia, which are dermal bones of the rays, and actinotrichia, which are non-mineralized spicules at the distal margin of the appendage. Little is known about the regenerative dynamics of the actinotrichia-specific structural proteins called Actinodins. Here, we used immunofluorescence analysis to determine the contribution of two paralogous Actinodin proteins, And1/2, in regenerating fins. Both proteins were detected in the secretory organelles in the mesenchymal cells of the blastema, but only And1 was detected in the epithelial cells of the wound epithelium. The analysis of whole mount fins throughout the entire regenerative process and longitudinal sections revealed that And1-positive fibers are complementary to the lepidotrichia. The analysis of another longfin fish, a gain-of-function mutation in the potassium channel kcnk5b, revealed that the long-fin phenotype is associated with an extended size of actinotrichia during homeostasis and regeneration. Finally, we investigated the role of several signaling pathways in actinotrichia formation and maintenance. This revealed that the pulse-inhibition of either TGFβ/Activin-βA or FGF are sufficient to impair deposition of Actinodin during regeneration. Thus, the dynamic turnover of Actinodin during fin regeneration is regulated by multiple factors, including the osteoblasts, growth rate in a potassium channel mutant, and instructive signaling networks between the epithelium and the blastema of the regenerating fin.}, } @article {pmid28757112, year = {2018}, author = {Lai, AG and Kosaka, N and Abnave, P and Sahu, S and Aboobaker, AA}, title = {The abrogation of condensin function provides independent evidence for defining the self-renewing population of pluripotent stem cells.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {218-226}, pmid = {28757112}, issn = {1095-564X}, support = {MR/M000133/1//Medical Research Council/United Kingdom ; BB/K007564/1//Biotechnology and Biological Sciences Research Council/United Kingdom ; }, mesh = {Adenosine Triphosphatases/antagonists & inhibitors/genetics/*physiology ; Adult Stem Cells/*physiology ; Animals ; Apoptosis ; Cell Division ; *Cell Self Renewal ; Chromosome Segregation/physiology ; DNA-Binding Proteins/antagonists & inhibitors/genetics/*physiology ; Endoreduplication ; Gamma Rays ; Gene Expression Regulation ; Helminth Proteins/*physiology ; Mitosis ; Multiprotein Complexes/antagonists & inhibitors/genetics/*physiology ; Phenotype ; Phylogeny ; Planarians/cytology/*physiology/radiation effects ; Pluripotent Stem Cells/*physiology ; RNA Interference ; RNA, Small Interfering/genetics ; Regeneration/*physiology ; }, abstract = {Heterogeneity of planarian stem cells has been categorised on the basis of single cell expression analyses and subsequent experiments to demonstrate lineage relationships. Some data suggest that despite heterogeneity in gene expression amongst cells in the cell cycle, in fact only one sub-population, known as sigma neoblasts, can self-renew. Without the tools to perform live in vivo lineage analysis, we instead took an alternative approach to provide independent evidence for defining the self-renewing stem cell population. We exploited the role of highly conserved condensin family genes to functionally assay neoblast self-renewal properties. Condensins are involved in forming properly condensed chromosomes to allow cell division to proceed during mitosis, and their abrogation inhibits mitosis and can lead to repeated endoreplication of the genome in cells that make repeated attempts to divide. We find that planarians possess only the condensin I complex, and that this is required for normal stem cell function. Abrogation of condensin function led to rapid stem cell depletion accompanied by the appearance of 'giant' cells with increased DNA content. Using previously discovered markers of heterogeneity we show that enlarged cells are always from the sigma-class of the neoblast population and we never observe evidence for endoreplication for the other neoblast subclasses. Overall, our data establish that condensins are essential for stem cell maintenance and provide independent evidence that only sigma-neoblasts are capable of multiple rounds of cell division and hence self-renewal.}, } @article {pmid28757111, year = {2018}, author = {Lengerer, B and Wunderer, J and Pjeta, R and Carta, G and Kao, D and Aboobaker, A and Beisel, C and Berezikov, E and Salvenmoser, W and Ladurner, P}, title = {Organ specific gene expression in the regenerating tail of Macrostomum lignano.}, journal = {Developmental biology}, volume = {433}, number = {2}, pages = {448-460}, doi = {10.1016/j.ydbio.2017.07.021}, pmid = {28757111}, issn = {1095-564X}, mesh = {Animals ; *Gene Expression Regulation ; *Genes, Helminth ; Helminth Proteins/biosynthesis/*genetics ; Hermaphroditic Organisms ; In Situ Hybridization ; Microvilli ; Organ Specificity ; Platyhelminths/genetics/*physiology ; RNA Interference ; RNA, Helminth/biosynthesis/genetics ; RNA, Messenger/biosynthesis/genetics ; Regeneration/*genetics/physiology ; Tail/*physiology ; Transcriptome ; Wound Healing/genetics ; }, abstract = {Temporal and spatial characterization of gene expression is a prerequisite for the understanding of cell-, tissue-, and organ-differentiation. In a multifaceted approach to investigate gene expression in the tail plate of the free-living marine flatworm Macrostomum lignano, we performed a posterior-region-specific in situ hybridization screen, RNA sequencing (RNA-seq) of regenerating animals, and functional analyses of selected tail-specific genes. The in situ screen revealed transcripts expressed in the antrum, cement glands, adhesive organs, prostate glands, rhabdite glands, and other tissues. Next we used RNA-seq to characterize temporal expression in the regenerating tail plate revealing a time restricted onset of both adhesive organs and copulatory apparatus regeneration. In addition, we identified three novel previously unannotated genes solely expressed in the regenerating stylet. RNA interference showed that these genes are required for the formation of not only the stylet but the whole male copulatory apparatus. RNAi treated animals lacked the stylet, vesicula granulorum, seminal vesicle, false seminal vesicle, and prostate glands, while the other tissues of the tail plate, such as adhesive organs regenerated normally. In summary, our findings provide a large resource of expression data during homeostasis and regeneration of the morphologically complex tail regeneration and pave the way for a better understanding of organogenesis in M. lignano.}, } @article {pmid28755787, year = {2018}, author = {Pante, MC and de la Torre, I}, title = {A hidden treasure of the Lower Pleistocene at Olduvai Gorge, Tanzania: The Leakey HWK EE assemblage.}, journal = {Journal of human evolution}, volume = {120}, number = {}, pages = {114-139}, doi = {10.1016/j.jhevol.2017.06.006}, pmid = {28755787}, issn = {1095-8606}, abstract = {HWK EE is a little-known archaeological site from the top of Lower Bed II and the basal part of Middle Bed II, Olduvai Gorge, Tanzania. The site was originally excavated in the early 1970s by Mary Leakey, but the excavations and resulting lithic and fossil assemblages were never described. Here we report for the first time on the lithic and fossil assemblages that were recovered by Mary Leakey from the site. The lithic assemblage is one of the largest of any Oldowan site and is characterized by a core-and-flake technology with simple flaking techniques and minimal reduction of cores. Retouched flake frequencies and battered tools are higher than those reported for Olduvai Bed I and Lower Bed II assemblages, but flaking schemes are poorly organized. The fossil assemblage is well-preserved, taxonomically-rich, but dominated by bovids, and includes abundant feeding traces of both hominins and carnivores. Hominins are inferred to have broken the majority of limb bones at the site for access to marrow, while both carnivores and hominins likely had access to at least some flesh. HWK EE may represent one of the last Homo habilis sites at Olduvai Gorge, and is important to understanding the behavioral and cultural mechanisms that led to the emergence of the Acheulean and Homo erectus in the region.}, } @article {pmid28752629, year = {2018}, author = {Genoud, M and Isler, K and Martin, RD}, title = {Comparative analyses of basal rate of metabolism in mammals: data selection does matter.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {404-438}, doi = {10.1111/brv.12350}, pmid = {28752629}, issn = {1469-185X}, abstract = {Basal rate of metabolism (BMR) is a physiological parameter that should be measured under strictly defined experimental conditions. In comparative analyses among mammals BMR is widely used as an index of the intensity of the metabolic machinery or as a proxy for energy expenditure. Many databases with BMR values for mammals are available, but the criteria used to select metabolic data as BMR estimates have often varied and the potential effect of this variability has rarely been questioned. We provide a new, expanded BMR database reflecting compliance with standard criteria (resting, postabsorptive state; thermal neutrality; adult, non-reproductive status for females) and examine potential effects of differential selectivity on the results of comparative analyses. The database includes 1739 different entries for 817 species of mammals, compiled from the original sources. It provides information permitting assessment of the validity of each estimate and presents the value closest to a proper BMR for each entry. Using different selection criteria, several alternative data sets were extracted and used in comparative analyses of (i) the scaling of BMR to body mass and (ii) the relationship between brain mass and BMR. It was expected that results would be especially dependent on selection criteria with small sample sizes and with relatively weak relationships. Phylogenetically informed regression (phylogenetic generalized least squares, PGLS) was applied to the alternative data sets for several different clades (Mammalia, Eutheria, Metatheria, or individual orders). For Mammalia, a 'subsampling procedure' was also applied, in which random subsamples of different sample sizes were taken from each original data set and successively analysed. In each case, two data sets with identical sample size and species, but comprising BMR data with different degrees of reliability, were compared. Selection criteria had minor effects on scaling equations computed for large clades (Mammalia, Eutheria, Metatheria), although less-reliable estimates of BMR were generally about 12-20% larger than more-reliable ones. Larger effects were found with more-limited clades, such as sciuromorph rodents. For the relationship between BMR and brain mass the results of comparative analyses were found to depend strongly on the data set used, especially with more-limited, order-level clades. In fact, with small sample sizes (e.g. <100) results often appeared erratic. Subsampling revealed that sample size has a non-linear effect on the probability of a zero slope for a given relationship. Depending on the species included, results could differ dramatically, especially with small sample sizes. Overall, our findings indicate a need for due diligence when selecting BMR estimates and caution regarding results (even if seemingly significant) with small sample sizes.}, } @article {pmid28745003, year = {2018}, author = {Müller, V and de Boer, RJ and Bonhoeffer, S and Szathmáry, E}, title = {An evolutionary perspective on the systems of adaptive immunity.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {505-528}, doi = {10.1111/brv.12355}, pmid = {28745003}, issn = {1469-185X}, abstract = {We propose an evolutionary perspective to classify and characterize the diverse systems of adaptive immunity that have been discovered across all major domains of life. We put forward a new function-based classification according to the way information is acquired by the immune systems: Darwinian immunity (currently known from, but not necessarily limited to, vertebrates) relies on the Darwinian process of clonal selection to 'learn' by cumulative trial-and-error feedback; Lamarckian immunity uses templated targeting (guided adaptation) to internalize heritable information on potential threats; finally, shotgun immunity operates through somatic mechanisms of variable targeting without feedback. We argue that the origin of Darwinian (but not Lamarckian or shotgun) immunity represents a radical innovation in the evolution of individuality and complexity, and propose to add it to the list of major evolutionary transitions. While transitions to higher-level units entail the suppression of selection at lower levels, Darwinian immunity re-opens cell-level selection within the multicellular organism, under the control of mechanisms that direct, rather than suppress, cell-level evolution for the benefit of the individual. From a conceptual point of view, the origin of Darwinian immunity can be regarded as the most radical transition in the history of life, in which evolution by natural selection has literally re-invented itself. Furthermore, the combination of clonal selection and somatic receptor diversity enabled a transition from limited to practically unlimited capacity to store information about the antigenic environment. The origin of Darwinian immunity therefore comprises both a transition in individuality and the emergence of a new information system - the two hallmarks of major evolutionary transitions. Finally, we present an evolutionary scenario for the origin of Darwinian immunity in vertebrates. We propose a revival of the concept of the 'Big Bang' of vertebrate immunity, arguing that its origin involved a 'difficult' (i.e. low-probability) evolutionary transition that might have occurred only once, in a common ancestor of all vertebrates. In contrast to the original concept, we argue that the limiting innovation was not the generation of somatic diversity, but the regulatory circuitry needed for the safe operation of amplifiable immune responses with somatically acquired targeting. Regulatory complexity increased abruptly by genomic duplications at the root of the vertebrate lineage, creating a rare opportunity to establish such circuitry. We discuss the selection forces that might have acted at the origin of the transition, and in the subsequent stepwise evolution leading to the modern immune systems of extant vertebrates.}, } @article {pmid28736447, year = {2018}, author = {Hegge, JW and Swarts, DC and van der Oost, J}, title = {Prokaryotic Argonaute proteins: novel genome-editing tools?.}, journal = {Nature reviews. Microbiology}, volume = {16}, number = {1}, pages = {5-11}, pmid = {28736447}, issn = {1740-1534}, mesh = {Argonaute Proteins/chemistry/*metabolism ; DNA/genetics/metabolism ; Gene Editing/methods ; Prokaryotic Cells/*metabolism ; Protein Binding ; Protein Interaction Domains and Motifs ; RNA Interference ; }, abstract = {Argonaute proteins constitute a highly diverse family of nucleic acid-guided proteins. They were first discovered in eukaryotes as key proteins in RNA interference systems, but homologous prokaryotic Argonaute proteins (pAgos) have also been found in archaea and bacteria. In this Progress article, we focus on long pAgo variants, a class of pAgos that are involved in nucleic acid-guided host defence against invading nucleic acids, and discuss the potential of pAgos in genome editing.}, } @article {pmid28734616, year = {2018}, author = {Pensinger, DA and Schaenzer, AJ and Sauer, JD}, title = {Do Shoot the Messenger: PASTA Kinases as Virulence Determinants and Antibiotic Targets.}, journal = {Trends in microbiology}, volume = {26}, number = {1}, pages = {56-69}, pmid = {28734616}, issn = {1878-4380}, support = {R01 CA188034/CA/NCI NIH HHS/United States ; }, mesh = {Anti-Bacterial Agents/*pharmacology ; Bacteria/drug effects/metabolism ; Bacterial Proteins/metabolism ; Biofilms/growth & development ; Cell Division/physiology ; Cell Wall ; Drug Resistance, Bacterial/*physiology ; Gene Expression Regulation, Bacterial ; Histidine Kinase ; Homeostasis ; Membrane Proteins/metabolism ; Penicillin-Binding Proteins ; Phosphorylation ; Protein Domains ; Protein Kinases/metabolism ; Protein-Serine-Threonine Kinases/*drug effects/genetics/*metabolism ; Signal Transduction ; Virulence ; Virulence Factors/*metabolism ; beta-Lactam Resistance/physiology ; }, abstract = {All domains of life utilize protein phosphorylation as a mechanism of signal transduction. In bacteria, protein phosphorylation was classically thought to be mediated exclusively by histidine kinases as part of two-component signaling systems. However, it is now well appreciated that eukaryotic-like serine/threonine kinases (eSTKs) control essential processes in bacteria. A subset of eSTKs are single-pass transmembrane proteins that have extracellular penicillin-binding-protein and serine/threonine kinase-associated (PASTA) domains which bind muropeptides. In a variety of important pathogens, PASTA kinases have been implicated in regulating biofilms, antibiotic resistance, and ultimately virulence. Although there are limited examples of direct regulation of virulence factors, PASTA kinases are critical for virulence due to their roles in regulating bacterial physiology in the context of stress. This review focuses on the role of PASTA kinases in virulence for a variety of important Gram-positive pathogens and concludes with a discussion of current efforts to develop kinase inhibitors as novel antimicrobials.}, } @article {pmid28716894, year = {2018}, author = {Whitehead, SS and Subbarao, K}, title = {Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Risks of Incomplete Immunity to Dengue Virus Revealed by Vaccination.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a028811}, pmid = {28716894}, issn = {1943-0264}, abstract = {Immune enhancement of dengue disease continues to be a concern for those with incomplete immunity in endemic areas. Advanced testing and follow-up of a newly available live attenuated dengue vaccine has recently shown the ability of vaccination to predispose some recipients for a severe outcome on subsequent infection. To improve safety, recommendations have been made to restrict use of the vaccine to those who are likely to have had prior exposure to dengue virus (DENV). Researchers continue to investigate dengue immunity and seek evidence that dengue vaccines can be safely administered to all populations needing protection.}, } @article {pmid28716893, year = {2018}, author = {Halstead, SB}, title = {Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? There Is Only One True Winner.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a030700}, pmid = {28716893}, issn = {1943-0264}, abstract = {The scientific community now possesses information obtained directly from human beings that makes it possible to understand why breakthrough-enhanced dengue virus (DENV) infections occurred in children receiving Sanofi Pasteur's Dengvaxia tetravalent live attenuated vaccine and to predict the possibility of breakthrough-enhanced DENV infections following immunization with two other tetravalent live attenuated vaccines now in phase III testing. Based upon recent research, Dengvaxia, lacking DENV nonstructural protein antigens, did not protect seronegatives because it failed to raise a competent T-cell response and/or antibodies to NS1. It is also possible that chimeric structure does not present the correct virion conformation permitting the development of protective neutralizing antibodies. A premonitory signal shared by the Sanofi Pasteur and the Takeda vaccines was the failure of fully immunized subhuman primates to prevent low-level viremia and/or anamnestic antibody responses to live DENV challenge. The vaccine developed by the National Institute of Allergy and Infectious Diseases (National Institutes of Health [NIH]) has met virtually all of the goals needed to demonstrate preclinical efficacy and safety for humans. Each monovalent vaccine was comprehensively studied for reactogenicity and immunogenicity in human volunteers. Protective immunity in subjects receiving tetravalent candidate vaccines was evidenced by the fact that when vaccinated subjects were given further doses of vaccine or different strains of DENV the result was "solid immunity," a nonviremic and nonanamnestic immune response.}, } @article {pmid28716892, year = {2018}, author = {Guy, B}, title = {Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? Questions Raised by the Development and Implementation of Dengue Vaccines: Example of the Sanofi Pasteur Tetravalent Dengue Vaccine.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a029462}, pmid = {28716892}, issn = {1943-0264}, abstract = {Dengue is a still-growing public health concern in many tropical and subtropical regions of the world. The development and implementation of an effective dengue vaccine in these regions is a high priority. This insight focuses on the expected characteristics of a safe and efficacious vaccine, referring to the clinical experience obtained during the development of the first tetravalent dengue vaccine from Sanofi Pasteur, now licensed in several endemic countries. Safety and efficacy data from both short- and long-term follow-up of large-scale efficacy studies will be discussed, as well as the next steps following vaccine introduction.}, } @article {pmid28716891, year = {2018}, author = {de Silva, AM and Harris, E}, title = {Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Path to a Dengue Vaccine: Learning from Human Natural Dengue Infection Studies and Vaccine Trials.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, pmid = {28716891}, issn = {1943-0264}, support = {P01 AI106695/AI/NIAID NIH HHS/United States ; R01 AI107731/AI/NIAID NIH HHS/United States ; R01 AI125198/AI/NIAID NIH HHS/United States ; }, abstract = {Dengue virus (DENV) is the most common arthropod-borne viral disease of humans. Although effective vaccines exist against other flaviviral diseases like yellow fever and Japanese encephalitis, dengue vaccine development is complicated by the presence of four virus serotypes and the possibility of partial immunity enhancing dengue disease severity. Several live attenuated dengue vaccines are being tested in human clinical trials. Initial results are mixed, with variable efficacy depending on DENV serotype and previous DENV exposure. Here, we highlight recent discoveries about the human antibody response to DENV and propose guidelines for advancing development of safe and effective dengue vaccines.}, } @article {pmid28716890, year = {2018}, author = {Yoshimura, A and Ito, M and Chikuma, S and Akanuma, T and Nakatsukasa, H}, title = {Negative Regulation of Cytokine Signaling in Immunity.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a028571}, pmid = {28716890}, issn = {1943-0264}, abstract = {Cytokines are key modulators of immunity. Most cytokines use the Janus kinase and signal transducers and activators of transcription (JAK-STAT) pathway to promote gene transcriptional regulation, but their signals must be attenuated by multiple mechanisms. These include the suppressors of cytokine signaling (SOCS) family of proteins, which represent a main negative regulation mechanism for the JAK-STAT pathway. Cytokine-inducible Src homology 2 (SH2)-containing protein (CIS), SOCS1, and SOCS3 proteins regulate cytokine signals that control the polarization of CD4+ T cells and the maturation of CD8+ T cells. SOCS proteins also regulate innate immune cells and are involved in tumorigenesis. This review summarizes recent progress on CIS, SOCS1, and SOCS3 in T cells and tumor immunity.}, } @article {pmid28716889, year = {2018}, author = {Hosokawa, H and Rothenberg, EV}, title = {Cytokines, Transcription Factors, and the Initiation of T-Cell Development.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, pmid = {28716889}, issn = {1943-0264}, support = {R01 AI095943/AI/NIAID NIH HHS/United States ; R01 HD076915/HD/NICHD NIH HHS/United States ; }, abstract = {Multipotent blood progenitor cells migrate into the thymus and initiate the T-cell differentiation program. T-cell progenitor cells gradually acquire T-cell characteristics while shedding their multipotentiality for alternative fates. This process is supported by extracellular signaling molecules, including Notch ligands and cytokines, provided by the thymic microenvironment. T-cell development is associated with dynamic change of gene regulatory networks of transcription factors, which interact with these environmental signals. Together with Notch or pre-T-cell-receptor (TCR) signaling, cytokines always control proliferation, survival, and differentiation of early T cells, but little is known regarding their cross talk with transcription factors. However, recent results suggest ways that cytokines expressed in distinct intrathymic niches can specifically modulate key transcription factors. This review discusses how stage-specific roles of cytokines and transcription factors can jointly guide development of early T cells.}, } @article {pmid28716888, year = {2018}, author = {Yan, J and Smyth, MJ and Teng, MWL}, title = {Interleukin (IL)-12 and IL-23 and Their Conflicting Roles in Cancer.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a028530}, pmid = {28716888}, issn = {1943-0264}, abstract = {The balance of proinflammatory cytokines interleukin (IL)-12 and IL-23 plays a key role in shaping the development of antitumor or protumor immunity. In this review, we discuss the role IL-12 and IL-23 plays in tumor biology from preclinical and clinical data. In particular, we discuss the mechanism by which IL-23 promotes tumor growth and metastases and how the IL-12/IL-23 axis of inflammation can be targeted for cancer therapy.}, } @article {pmid28716887, year = {2018}, author = {Chiasson-MacKenzie, C and McClatchey, AI}, title = {Cell-Cell Contact and Receptor Tyrosine Kinase Signaling.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a029215}, pmid = {28716887}, issn = {1943-0264}, abstract = {The behavior of cells within tissues is governed by the activities of adhesion receptors that provide spatial cues and transmit forces through intercellular junctions, and by growth-factor receptors, particularly receptor tyrosine kinases (RTKs), that respond to biochemical signals from the environment. Coordination of these two activities is essential for the patterning and polarized migration of cells during morphogenesis and for homeostasis in mature tissues; loss of this coordination is a hallmark of developing cancer and driver of metastatic progression. Although much is known about the individual functions of adhesion and growth factor receptors, we have a surprisingly superficial understanding of the mechanisms by which their activities are coordinated.}, } @article {pmid28716886, year = {2018}, author = {Erkkinen, MG and Kim, MO and Geschwind, MD}, title = {Clinical Neurology and Epidemiology of the Major Neurodegenerative Diseases.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, doi = {10.1101/cshperspect.a033118}, pmid = {28716886}, issn = {1943-0264}, support = {T32 AG023481/AG/NIA NIH HHS/United States ; }, abstract = {Neurodegenerative diseases are a common cause of morbidity and cognitive impairment in older adults. Most clinicians who care for the elderly are not trained to diagnose these conditions, perhaps other than typical Alzheimer's disease (AD). Each of these disorders has varied epidemiology, clinical symptomatology, laboratory and neuroimaging features, neuropathology, and management. Thus, it is important that clinicians be able to differentiate and diagnose these conditions accurately. This review summarizes and highlights clinical aspects of several of the most commonly encountered neurodegenerative diseases, including AD, frontotemporal dementia (FTD) and its variants, progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), Parkinson's disease (PD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), and Huntington's disease (HD). For each condition, we provide a brief overview of the epidemiology, defining clinical symptoms and diagnostic criteria, relevant imaging and laboratory features, genetics, pathology, treatments, and differential diagnosis.}, } @article {pmid28716885, year = {2018}, author = {Carpenter, S and Fitzgerald, KA}, title = {Cytokines and Long Noncoding RNAs.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a028589}, pmid = {28716885}, issn = {1943-0264}, support = {R01 AI079293/AI/NIAID NIH HHS/United States ; R37 AI067497/AI/NIAID NIH HHS/United States ; }, abstract = {Cytokines and long noncoding RNAs (lncRNAs) are intertwined in the regulatory circuit controlling immunity. lncRNA expression levels are altered following cytokine stimulation in a cell-type-specific fashion. lncRNAs, in turn, regulate the inducible expression of cytokines following immune activation. These studies position lncRNAs as important regulators of gene expression within the complex pathways of the immune system. Our understanding of the functions of lncRNAs is just beginning. Current methodologies for functionally understanding how these transcripts mediate their effects are unable to keep up with the speed of genomic outputs cataloging thousands of these novel genes. In this review, we highlight the interplay between cytokines and lncRNAs and speculate on the future utility of these genes as potential biomarkers and therapeutic targets for the treatment of inflammatory disorders.}, } @article {pmid28716884, year = {2018}, author = {Screaton, G and Mongkolsapaya, J}, title = {Which Dengue Vaccine Approach Is the Most Promising, and Should We Be Concerned about Enhanced Disease after Vaccination? The Challenges of a Dengue Vaccine.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a029520}, pmid = {28716884}, issn = {1943-0264}, abstract = {A dengue vaccine has been pursued for more than 50 years and, unlike other flaviviral vaccines such as that against yellow fever, progress has been slow. In this review, we describe progress toward the first licensed dengue vaccine Dengvaxia, which does not give complete protection against disease. The antibody response to the dengue virion is reviewed, highlighting immunodominant yet poorly neutralizing responses in the context of a highly dynamic structurally flexible dengue virus particle. Finally, we review recent evidence for cross-reactivity between antibody responses to Zika and dengue viruses, which may further complicate the development of broadly protective dengue virus vaccines.}, } @article {pmid28716883, year = {2018}, author = {Hercus, TR and Kan, WLT and Broughton, SE and Tvorogov, D and Ramshaw, HS and Sandow, JJ and Nero, TL and Dhagat, U and Thompson, EJ and Shing, KSCT and McKenzie, DR and Wilson, NJ and Owczarek, CM and Vairo, G and Nash, AD and Tergaonkar, V and Hughes, T and Ekert, PG and Samuel, MS and Bonder, CS and Grimbaldeston, MA and Parker, MW and Lopez, AF}, title = {Role of the β Common (βc) Family of Cytokines in Health and Disease.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a028514}, pmid = {28716883}, issn = {1943-0264}, abstract = {The β common ([βc]/CD131) family of cytokines comprises granulocyte macrophage colony-stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5, all of which use βc as their key signaling receptor subunit. This is a prototypic signaling subunit-sharing cytokine family that has unveiled many biological paradigms and structural principles applicable to the IL-2, IL-4, and IL-6 receptor families, all of which also share one or more signaling subunits. Originally identified for their functions in the hematopoietic system, the βc cytokines are now known to be truly pleiotropic, impacting on multiple cell types, organs, and biological systems, and thereby controlling the balance between health and disease. This review will focus on the emerging biological roles for the βc cytokines, our progress toward understanding the mechanisms of receptor assembly and signaling, and the application of this knowledge to develop exciting new therapeutic approaches against human disease.}, } @article {pmid28702783, year = {2018}, author = {Aydinoglu, AU and Taşkın, Z}, title = {Origins of Life Research: a Bibliometric Approach.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {55-71}, doi = {10.1007/s11084-017-9543-4}, pmid = {28702783}, issn = {1573-0875}, mesh = {*Bibliometrics ; *Exobiology ; *Origin of Life ; Research ; }, abstract = {This study explores the collaborative nature and interdisciplinarity of the origin(s) of life (OoL) research community. Although OoL research is one of the oldest topics in philosophy, religion, and science; to date there has been no review of the field utilizing bibliometric measures. A dataset of 5647 publications that are tagged as OoL, astrobiology, exobiology, and prebiotic chemistry is analyzed. The most prolific authors (Raulin, Ehrenfreund, McKay, Cleaves, Cockell, Lazcano, etc.), most cited scholars and their articles (Miller 1953, Gilbert 1986, Chyba & Sagan 1992, Wȁchtershȁuser 1988, etc.), and popular journals (Origins of Life and Evolution of Biospheres and Astrobiology) for OoL research are identified. Moreover, interdisciplinary research conducted through research networks, institutions (NASA, Caltech, University of Arizona, University of Washington, CNRS, etc.), and keywords & concepts (astrobiology, life, Mars, amino acid, prebiotic chemistry, evolution, RNA) are explored.}, } @article {pmid28699275, year = {2018}, author = {Phillips, T}, title = {The concepts of asymmetric and symmetric power can help resolve the puzzle of altruistic and cooperative behaviour.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {457-468}, doi = {10.1111/brv.12352}, pmid = {28699275}, issn = {1469-185X}, abstract = {Evolutionary theory predicts competition in nature yet altruistic and cooperative behaviour appears to reduce the ability to compete in order to help others compete better. This evolutionary puzzle is usually explained by kin selection where close relatives perform altruistic and cooperative acts to help each other and by reciprocity theory (i.e. direct, indirect and generalized reciprocity) among non-kin. Here, it is proposed that the concepts of asymmetry and symmetry in power and dominance are critical if we are ever to resolve the puzzle of altruism and cooperation towards non-kin. Asymmetry in power and dominance is likely to emerge under competition in nature as individuals strive to gain greater access to the scarce resources needed to survive and reproduce successfully. Yet asymmetric power presents serious problems for reciprocity theory in that a dominant individual faces a temptation to cheat in interactions with subordinates that is likely to far outweigh any individual selective benefits gained through reciprocal mechanisms. Furthermore, action taken by subordinates to deter non-reciprocation by dominants is likely to prove prohibitively costly to their fitness, making successful enforcement of reciprocal mechanisms unlikely. It is also argued here that many apparently puzzling forms of cooperation observed in nature (e.g. cooperative breeding in which unrelated subordinates help dominants to breed) might be best explained by asymmetry in power and dominance. Once it is recognized that individuals in these cooperative interactions are subject to the constraints and opportunities imposed on them by asymmetric power then they can be seen as pursuing a 'least bad' strategy to promote individual fitness - one that is nevertheless consistent with evolutionary theory. The concept of symmetric power also provides important insights. It can inhibit reciprocal mechanisms in the sense that symmetric power makes it easier for a cheat to appropriate common resources while incurring fewer penalties. Nevertheless under certain restrictive conditions, symmetric power is seen as likely to promote direct reciprocity through 'tit for tat'.}, } @article {pmid28695682, year = {2018}, author = {Hisano, M and Searle, EB and Chen, HYH}, title = {Biodiversity as a solution to mitigate climate change impacts on the functioning of forest ecosystems.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {439-456}, doi = {10.1111/brv.12351}, pmid = {28695682}, issn = {1469-185X}, abstract = {Forest ecosystems are critical to mitigating greenhouse gas emissions through carbon sequestration. However, climate change has affected forest ecosystem functioning in both negative and positive ways, and has led to shifts in species/functional diversity and losses in plant species diversity which may impair the positive effects of diversity on ecosystem functioning. Biodiversity may mitigate climate change impacts on (I) biodiversity itself, as more-diverse systems could be more resilient to climate change impacts, and (II) ecosystem functioning through the positive relationship between diversity and ecosystem functioning. By surveying the literature, we examined how climate change has affected forest ecosystem functioning and plant diversity. Based on the biodiversity effects on ecosystem functioning (B→EF), we specifically address the potential for biodiversity to mitigate climate change impacts on forest ecosystem functioning. For this purpose, we formulate a concept whereby biodiversity may reduce the negative impacts or enhance the positive impacts of climate change on ecosystem functioning. Further B→EF studies on climate change in natural forests are encouraged to elucidate how biodiversity might influence ecosystem functioning. This may be achieved through the detailed scrutiny of large spatial/long temporal scale data sets, such as long-term forest inventories. Forest management strategies based on B→EF have strong potential for augmenting the effectiveness of the roles of forests in the mitigation of climate change impacts on ecosystem functioning.}, } @article {pmid28689315, year = {2018}, author = {Doan, TN and Fujihara, A}, title = {Enantiomer-Selective Photo-Induced Reaction of Protonated Tryptophan with Disaccharides in the Gas Phase.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {123-130}, doi = {10.1007/s11084-017-9544-3}, pmid = {28689315}, issn = {1573-0875}, mesh = {Disaccharides/*chemistry ; *Evolution, Chemical ; Gases/*chemistry ; Molecular Structure ; *Photolysis ; Stereoisomerism ; Tandem Mass Spectrometry ; Tryptophan/*chemistry ; }, abstract = {In order to investigate chemical evolution in interstellar molecular clouds, enantiomer-selective photo-induced chemical reactions between an amino acid and disaccharides in the gas phase were examined using a tandem mass spectrometer containing an electrospray ionization source and a cold ion trap. Ultraviolet photodissociation mass spectra of cold gas-phase noncovalent complexes of protonated tryptophan (Trp) enantiomers with disaccharides consisting of two D-glucose units, such as D-maltose or D-cellobiose, were obtained by photoexcitation of the indole ring of Trp. NH2CHCOOH loss via cleavage of the Cα-Cβ bond in Trp induced by hydrogen atom transfer from the NH3+ group of a protonated Trp was observed in a noncovalent heterochiral H+(L-Trp)(D-maltose) complex. In contrast, a photo-induced chemical reaction forming the product ion with m/z 282 occurs in homochiral H+(D-Trp)(D-maltose). For D-cellobiose, both NH2CHCOOH elimination and the m/z 282 product ion were observed, and no enantiomer-selective phenomena occurred. The m/z 282 product ion indicates that the photo-induced C-glycosylation, which links D-glucose residues to the indole moiety of Trp via a C-C bond, can occur in cold gas-phase noncovalent complexes, and its enantiomer-selectivity depends on the structure of the disaccharide.}, } @article {pmid28685374, year = {2018}, author = {Cantine, MD and Fournier, GP}, title = {Environmental Adaptation from the Origin of Life to the Last Universal Common Ancestor.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {35-54}, doi = {10.1007/s11084-017-9542-5}, pmid = {28685374}, issn = {1573-0875}, support = {NNA13AA90A//National Aeronautics and Space Administration/ ; 339603//Simons Foundation/ ; }, mesh = {*Adaptation, Biological ; *Environment ; *Origin of Life ; Phylogeny ; }, abstract = {Extensive fundamental molecular and biological evolution took place between the prebiotic origins of life and the state of the Last Universal Common Ancestor (LUCA). Considering the evolutionary innovations between these two endpoints from the perspective of environmental adaptation, we explore the hypothesis that LUCA was temporally, spatially, and environmentally distinct from life's earliest origins in an RNA world. Using this lens, we interpret several molecular biological features as indicating an environmental transition between a cold, radiation-shielded origin of life and a mesophilic, surface-dwelling LUCA. Cellularity provides motility and permits Darwinian evolution by connecting genetic material and its products, and thus establishing heredity and lineage. Considering the importance of compartmentalization and motility, we propose that the early emergence of cellularity is required for environmental dispersal and diversification during these transitions. Early diversification and the emergence of ecology before LUCA could be an important pre-adaptation for life's persistence on a changing planet.}, } @article {pmid28675687, year = {2018}, author = {Bienenstock, J and Kunze, WA and Forsythe, P}, title = {Disruptive physiology: olfaction and the microbiome-gut-brain axis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {390-403}, doi = {10.1111/brv.12348}, pmid = {28675687}, issn = {1469-185X}, abstract = {This review covers the field of olfaction and chemosensation of odorants and puts this information into the context of interactions between microbes and behaviour; the microbiome-gut-brain axis (MGBA). Recent emphasis has also been placed on the concept of the holobiome which states that no single aspect of an organism should be viewed separately and thus must include examination of their associated microbial populations and their influence. While it is known that the microbiome may be involved in the modulation of animal behaviour, there has been little systematized effort to incorporate into such studies the rapidly developing knowledge of the wide range of olfactory systems. The classical olfactory system is evolutionarily conserved in multiple taxa from insects through to fish, reptiles and mammals, and is represented by the largest gene families in vertebrates. Mice have over 1000 different olfactory receptors and humans about 400. They are distributed throughout the body and are even found in spermatozoa where they function in chemotaxis. Each olfactory receptor has the unique functional capability of high-affinity binding to several different molecular ligands. These and other properties render the cataloguing of odorants (odorome) with specific actions a difficult task. Some ectopic olfactory receptors have been shown to have functional effects in the gut and kidney, highlighting the complexity of the systems engaged by odorants. However, there are, in addition to classical olfactory receptors, at least two other families of receptors involved in olfaction that are also widely found expressed on tissues in many different organs in addition to the nervous system and brain: the trace-amine associated and formyl peptide receptors. Bacteria can make many if not most odorants and are responsible for recognition of species and relative relatedness, as well as predator presence, among many other examples. Activation of different combinations of olfactory receptors by bacterial products such as β-phenylethylamine have been shown even to control expression of emotions such as fear and aggression. The number of examples of bacterial products and volatile odorants influencing brain function and behaviour is expanding rapidly. Since it is recognized that many different bacterial products and metabolites also function as social cues, and may themselves be directly or indirectly causative of behavioural change, it becomes ever more important to include olfaction into studies of the MGBA. Clearly there are broader implications for the involvement of olfaction in this rapidly evolving field. These include improvement in our understanding of the pathways engaged in various behaviours, and the identification of novel approaches and new targets in efforts to modulate behavioural changes.}, } @article {pmid28663210, year = {2018}, author = {Angeletti, D and Yewdell, JW}, title = {Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Outflanking Antibody Immunodominance on the Road to Universal Influenza Vaccination.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a028852}, pmid = {28663210}, issn = {1943-0264}, abstract = {Influenza remains a major human pathogen despite seasonal vaccination. At long last, there is energy and resources to develop influenza vaccines that provide more predictable and durable protection. Vaccines based on inducing antibodies to the conserved stem of the viral hemagglutinin (HA) have emerged as leading candidates for broadening population immunity and ultimately limiting antigenic drift. Here, we discuss the knowns and unknowns of HA-specific B-cell and antibody responses. In particular, we focus on how immunodominance sculpts antibody responses and drives antigenic drift. We propose a number of strategies to overcome immunodominance and improve the breadth and efficacy of antibody responses.}, } @article {pmid28663209, year = {2018}, author = {Krammer, F and García-Sastre, A and Palese, P}, title = {Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Potential Target Antigens and Critical Aspects for a Universal Influenza Vaccine.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a028845}, pmid = {28663209}, issn = {1943-0264}, abstract = {Influenza viruses cause seasonal epidemics as well as pandemics and are a significant concern for human health. Current influenza virus vaccines show efficacy when they are antigenically well matched to circulating strains. Seasonal influenza viruses undergo antigenic drift at a high rate and, therefore, current vaccines have to be reformulated and readministered on an annual basis. Mismatches between vaccine strains and circulating strains frequently occur, significantly decreasing vaccine efficacy. In addition, current seasonal influenza virus vaccines have limited efficacy against newly emerging pandemic viruses. A universal influenza virus vaccine that induces long-term protection against all influenza virus strains would abolish the need for annual readministration of seasonal influenza virus vaccines and would significantly enhance our pandemic preparedness. Here we discuss the characteristics of universal influenza virus vaccines, their potential target antigens, and critical aspects to consider on the path to successfully developing such vaccines.}, } @article {pmid28663208, year = {2018}, author = {Crowe, JE}, title = {Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Potential for a Universal Influenza Vaccine.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, pmid = {28663208}, issn = {1943-0264}, support = {HHSN272201400024C/AI/NIAID NIH HHS/United States ; R43 AI118087/AI/NIAID NIH HHS/United States ; U19 AI117905/AI/NIAID NIH HHS/United States ; }, abstract = {Development of optimal vaccines for influenza is challenging, in part as a result of the high antigenic variability in field strains associated with genetic shift from reassortment and genetic drift from point mutations. Discovery of conserved antigenic sites on the hemagglutinin (HA) protein for neutralizing antibodies suggested the possibility that influenza vaccines could be developed that induce focused antibody responses to the conserved neutralizing determinants, especially the HA stem region. Recent studies have focused on the antigenicity and immunogenicity of such domains, using monoclonal antibodies and candidate-engineered HA stem-based vaccines. Much progress has been made, but we still do not fully understand the biology of the immune response to this unique antigenic region.}, } @article {pmid28663207, year = {2018}, author = {Andrews, SF and Graham, BS and Mascola, JR and McDermott, AB}, title = {Is It Possible to Develop a "Universal" Influenza Virus Vaccine? Immunogenetic Considerations Underlying B-Cell Biology in the Development of a Pan-Subtype Influenza A Vaccine Targeting the Hemagglutinin Stem.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {7}, pages = {}, doi = {10.1101/cshperspect.a029413}, pmid = {28663207}, issn = {1943-0264}, abstract = {Current influenza vaccines preferentially generate B-cell responses to the variable hemagglutinin (HA) head. Focusing vaccine-induced antibody responses on epitopes in the conserved HA stem may provide better protection against future drifted and pandemic strains. Understanding the basis for the dominant HA head and subdominant HA stem-specific responses at the level of B-cell activation and differentiation will be critical for designing vaccines that induce sustained stem-specific responses. Identifying antibody lineages with broad neutralizing activity against influenza A viruses and defining the structural mode of recognition for germline precursors of those antibodies will also guide future immunogen design.}, } @article {pmid28660466, year = {2018}, author = {Zamudio, GS and José, MV}, title = {Identity Elements of tRNA as Derived from Information Analysis.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {73-81}, doi = {10.1007/s11084-017-9541-6}, pmid = {28660466}, issn = {1573-0875}, support = {737920//CONACYT/ ; PAPIIT-IN224015//DGAPA UNAM/ ; }, mesh = {Amino Acyl-tRNA Synthetases/*chemistry ; Anticodon/*chemistry ; Evolution, Molecular ; RNA, Transfer/*chemistry ; }, abstract = {The decipherment of the tRNA's operational code, known as the identity problem, requires the location of the sites in the tRNA structure that are involved in their correct recognition by the corresponding aminoacyl-tRNA synthetase. In this work, we determine the identity elements of each tRNA isoacceptor by means of the variation of information measure from information theory. We show that all isoacceptors exhibit sites associated with some bases of the anticodon. These sites form clusters that are scattered along the tRNA structure. The clusters determine the identity elements of each tRNA. We derive a catalogue of clustered sites for each tRNA that expands previously reported elements.}, } @article {pmid28643455, year = {2018}, author = {Al-Khawaga, S and Memon, B and Butler, AE and Taheri, S and Abou-Samra, AB and Abdelalim, EM}, title = {Pathways governing development of stem cell-derived pancreatic β cells: lessons from embryogenesis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {364-389}, doi = {10.1111/brv.12349}, pmid = {28643455}, issn = {1469-185X}, abstract = {The loss of functional β cells leads to development of diabetes. Several studies have shown that β cells are specified through several stages of progenitors during pancreas development, each stage defined by the expression of specific transcription factors (TFs). Understanding signalling pathways that control the differentiation and specification processes during embryogenesis will facilitate efforts to obtain functional β cells in vitro. Our current knowledge of the mechanisms involved in pancreatic β cell development and survival under normal or diabetic conditions has come largely from animal studies. However, there are marked differences in islet structure and physiological properties between humans and animals, and not all phenotypes of human diabetes can be recapitulated in animal models. Therefore, human pluripotent stem cells (hPSCs), including human embryonic stem cells (hESCs) and human induced PSCs (hiPSCs) offer a great opportunity for increasing our understanding of the pathways regulating human pancreatic β-cell development and survival. Furthermore, hPSCs provide a renewable source of functional pancreatic β cells for cell replacement therapy as well as disease modelling. Herein, we discuss the signalling pathways involved in the development of pancreatic β cells during embryogenesis. Additionally, we describe how these pathways are manipulated in vitro to differentiate hPSCs into functional β cells. Finally, we highlight the progress that has been made for the applications of those cells in treating and modelling diabetes.}, } @article {pmid28639360, year = {2018}, author = {Papa, S and Capitanio, G and Papa, F}, title = {The mechanism of coupling between oxido-reduction and proton translocation in respiratory chain enzymes.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {322-349}, doi = {10.1111/brv.12347}, pmid = {28639360}, issn = {1469-185X}, abstract = {The respiratory chain of mitochondria and bacteria is made up of a set of membrane-associated enzyme complexes which catalyse sequential, stepwise transfer of reducing equivalents from substrates to oxygen and convert redox energy into a transmembrane protonmotive force (PMF) by proton translocation from a negative (N) to a positive (P) aqueous phase separated by the coupling membrane. There are three basic mechanisms by which a membrane-associated redox enzyme can generate a PMF. These are membrane anisotropic arrangement of the primary redox catalysis with: (i) vectorial electron transfer by redox metal centres from the P to the N side of the membrane; (ii) hydrogen transfer by movement of quinones across the membrane, from a reduction site at the N side to an oxidation site at the P side; (iii) a different type of mechanism based on co-operative allosteric linkage between electron transfer at the metal redox centres and transmembrane electrogenic proton translocation by apoproteins. The results of advanced experimental and theoretical analyses and in particular X-ray crystallography show that these three mechanisms contribute differently to the protonmotive activity of cytochrome c oxidase, ubiquinone-cytochrome c oxidoreductase and NADH-ubiquinone oxidoreductase of the respiratory chain. This review considers the main features, recent experimental advances and still unresolved problems in the molecular/atomic mechanism of coupling between the transfer of reducing equivalents and proton translocation in these three protonmotive redox complexes.}, } @article {pmid28631442, year = {2018}, author = {Thiel, A and Reumann, MK and Boskey, A and Wischmann, J and von Eisenhart-Rothe, R and Mayer-Kuckuk, P}, title = {Osteoblast migration in vertebrate bone.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {350-363}, pmid = {28631442}, issn = {1469-185X}, support = {R01 AR041325/AR/NIAMS NIH HHS/United States ; }, abstract = {Bone formation, for example during bone remodelling or fracture repair, requires mature osteoblasts to deposit bone with remarkable spatial precision. As osteoblast precursors derive either from circulation or resident stem cell pools, they and their progeny are required to migrate within the three-dimensional bone space and to navigate to their destination, i.e. to the site of bone formation. An understanding of this process is emerging based on in vitro and in vivo studies of several vertebrate species. Receptors on the osteoblast surface mediate cell adhesion and polarization, which induces osteoblast migration. Osteoblast migration is then facilitated along gradients of chemoattractants. The latter are secreted or released proteolytically by several cell types interacting with osteoblasts, including osteoclasts and vascular endothelial cells. The positions of these cellular sources of chemoattractants in relation to the position of the osteoblasts provide the migrating osteoblasts with tracks to their destination, and osteoblasts possess the means to follow a track marked by multiple chemoattractant gradients. In addition to chemotactic cues, osteoblasts sense other classes of signals and utilize them as landmarks for navigation. The composition of the osseous surface guides adhesion and hence migration efficiency and can also provide steering through haptotaxis. Further, it is likely that signals received from surface interactions modulate chemotaxis. Besides the nature of the surface, mechanical signals such as fluid flow may also serve as navigation signals for osteoblasts. Alterations in osteoblast migration and navigation might play a role in metabolic bone diseases such as osteoporosis.}, } @article {pmid28630079, year = {2018}, author = {Victora, GD and Mouquet, H}, title = {What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Lessons from the Antibody Response to HIV-1.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a029389}, pmid = {28630079}, issn = {1943-0264}, abstract = {Most broadly neutralizing antibodies to HIV-1 have in common an extreme degree of somatic hypermutation (SHM), which correlates with their ability to neutralize multiple viral strains. However, achieving such extreme SHM by immunization remains a challenge. Here, we discuss how antigenic variation during HIV-1 infection may work to exacerbate SHM by permitting multiple iterative cycles of affinity maturation in germinal centers, and speculate on how this could be recapitulated through vaccination.}, } @article {pmid28630078, year = {2018}, author = {Toellner, KM and Sze, DM and Zhang, Y}, title = {What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? A Role for Antibody Feedback.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a028795}, pmid = {28630078}, issn = {1943-0264}, support = {G1001390//Medical Research Council/United Kingdom ; }, abstract = {We discuss the impact of antibody feedback on affinity maturation of B cells. Competition from epitope-specific antibodies produced earlier during the immune response leads to immune complex formation, which is essential for transport and deposition of antigen onto follicular dendritic cells (FDCs). It also reduces the concentration of free epitopes into the μm to nm range, which is essential for B-cell receptors (BCRs) to sense affinity-dependent changes in binding capacity. Antibody feedback may also induce epitope spreading, leading to a broader selection of epitopes recognized by newly emerging B-cell clones. This may be exploitable, providing ways to manipulate epitope usage induced by vaccination.}, } @article {pmid28630077, year = {2018}, author = {Kelsoe, G and Haynes, BF}, title = {What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Breaking through Immunity's Glass Ceiling.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, pmid = {28630077}, issn = {1943-0264}, support = {U19 AI117892/AI/NIAID NIH HHS/United States ; UM1 AI100645/AI/NIAID NIH HHS/United States ; }, abstract = {A key goal of HIV-1 vaccine development is the induction of broadly neutralizing antibodies (bnAbs) targeted to the vulnerable regions of the HIV envelope. BnAbs develop over time in ∼50% of HIV-1-infected individuals. However, to date, no vaccines have induced bnAbs and few or none of these vaccine-elicited HIV-1 antibodies carry the high frequencies of V(D)J mutations characteristic of bnAbs. Do the high frequencies of mutations characteristic of naturally induced bnAbs represent a fundamental barrier to the induction of bnAbs by vaccines? Recent studies suggest that high frequencies of V(D)J mutations can be achieved by serial vaccination strategies. Rather, it appears that, in the absence of HIV-1 infection, physiologic immune tolerance controls, including a germinal center process termed affinity reversion, may limit vaccine-driven bnAb development by clonal elimination or selecting for mutations incompatible with bnAb activity.}, } @article {pmid28630076, year = {2018}, author = {Stamper, CT and Wilson, PC}, title = {What Are the Primary Limitations in B-Cell Affinity Maturation, and How Much Affinity Maturation Can We Drive with Vaccination? Is Affinity Maturation a Self-Defeating Process for Eliciting Broad Protection?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, pmid = {28630076}, issn = {1943-0264}, support = {U19 AI057266/AI/NIAID NIH HHS/United States ; HHSN272201400006C/AI/NIAID NIH HHS/United States ; U19 AI109946/AI/NIAID NIH HHS/United States ; P01 AI097092/AI/NIAID NIH HHS/United States ; U19 AI082724/AI/NIAID NIH HHS/United States ; }, abstract = {Vaccinations are one of the greatest success stories of modern medicine, saving millions of lives since their widespread adoption. However, several diseases continue to elude highly effective vaccination strategies. Chief among these are human immunodeficiency virus (HIV) and influenza (flu), both of which will require vaccines that can guide the creation of highly mutated, broadly neutralizing antibodies (bnAbs). The generation of bnAbs is hindered by our inability to effectively drive the high levels of affinity maturation required to achieve them in a large number of cells. Major limitations placed on affinity maturation derives from the inherent mutability of immunoglobulin genes, the evolved activation-induced cytidine deaminase (AID) targeting mechanisms that exist within them, and biases in targeting of particular epitope B cells.}, } @article {pmid28620098, year = {2018}, author = {Toomer, KH and Malek, TR}, title = {Cytokine Signaling in the Development and Homeostasis of Regulatory T cells.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a028597}, pmid = {28620098}, issn = {1943-0264}, support = {F31 AI124629/AI/NIAID NIH HHS/United States ; R01 AI055815/AI/NIAID NIH HHS/United States ; R01 DK093866/DK/NIDDK NIH HHS/United States ; }, abstract = {Cytokine signaling is indispensable for regulatory T-cell (Treg) development in the thymus, and also influences the homeostasis, phenotypic diversity, and function of Tregs in the periphery. Because Tregs are required for establishment and maintenance of immunological self-tolerance, investigating the role of cytokines in Treg biology carries therapeutic potential in the context of autoimmune disease. This review discusses the potent and diverse influences of interleukin (IL)-2 signaling on the Treg compartment, an area of knowledge that has led to the use of low-dose IL-2 as a therapy to reregulate autoaggressive immune responses. Evidence suggesting Treg-specific impacts of the cytokines transforming growth factor β (TGF-β), IL-7, thymic stromal lymphopoietin (TSLP), IL-15, and IL-33 is also presented. Finally, we consider the technical challenges and knowledge limitations that must be overcome to bring other cytokine-based, Treg-targeted therapies into clinical use.}, } @article {pmid28620097, year = {2018}, author = {Monin, L and Gaffen, SL}, title = {Interleukin 17 Family Cytokines: Signaling Mechanisms, Biological Activities, and Therapeutic Implications.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, pmid = {28620097}, issn = {1943-0264}, support = {R01 DE022550/DE/NIDCR NIH HHS/United States ; R37 DE022550/DE/NIDCR NIH HHS/United States ; R01 AI107825/AI/NIAID NIH HHS/United States ; R21 AI128991/AI/NIAID NIH HHS/United States ; R01 AR062546/AR/NIAMS NIH HHS/United States ; }, abstract = {The cytokines of the interleukin 17 (IL-17) family play a central role in the control of infections, especially extracellular fungi. Conversely, if unrestrained, these inflammatory cytokines contribute to the pathology of numerous autoimmune and chronic inflammatory conditions. Recent advances have led to the approval of IL-17A-blocking biologics for the treatment of moderate to severe plaque psoriasis, but much remains to be understood about the biological functions, regulation, and signaling pathways downstream of these factors. In this review, we outline the current knowledge of signal transduction and known physiological activities of IL-17 family cytokines. We will highlight in particular the current understanding of these cytokines in the context of skin manifestations of disease.}, } @article {pmid28620096, year = {2018}, author = {Rose-John, S}, title = {Interleukin-6 Family Cytokines.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a028415}, pmid = {28620096}, issn = {1943-0264}, abstract = {The interleukin (IL)-6 family cytokines is a group of cytokines consisting of IL-6, IL-11, ciliary neurotrophic factor (CNTF), leukemia inhibitory factor (LIF), oncostatin M (OSM), cardiotrophin 1 (CT-1), cardiotrophin-like cytokine (CLC), and IL-27. They are grouped into one family because the receptor complex of each cytokine contains two (IL-6 and IL-11) or one molecule (all others cytokines) of the signaling receptor subunit gp130. IL-6 family cytokines have overlapping but also distinct biologic activities and are involved among others in the regulation of the hepatic acute phase reaction, in B-cell stimulation, in the regulation of the balance between regulatory and effector T cells, in metabolic regulation, and in many neural functions. Blockade of IL-6 family cytokines has been shown to be beneficial in autoimmune diseases, but bacterial infections and metabolic side effects have been observed. Recent advances in cytokine blockade might help to minimize such side effects during therapeutic blockade.}, } @article {pmid28620095, year = {2018}, author = {Stark, GR and Cheon, H and Wang, Y}, title = {Responses to Cytokines and Interferons that Depend upon JAKs and STATs.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, doi = {10.1101/cshperspect.a028555}, pmid = {28620095}, issn = {1943-0264}, abstract = {Many cytokines and all interferons activate members of a small family of kinases (the Janus kinases [JAKs]) and a slightly larger family of transcription factors (the signal transducers and activators of transcription [STATs]), which are essential components of pathways that induce the expression of specific sets of genes in susceptible cells. JAK-STAT pathways are required for many innate and acquired immune responses, and the activities of these pathways must be finely regulated to avoid major immune dysfunctions. Regulation is achieved through mechanisms that include the activation or induction of potent negative regulatory proteins, posttranslational modification of the STATs, and other modulatory effects that are cell-type specific. Mutations of JAKs and STATs can result in gains or losses of function and can predispose affected individuals to autoimmune disease, susceptibility to a variety of infections, or cancer. Here we review recent developments in the biochemistry, genetics, and biology of JAKs and STATs.}, } @article {pmid28602430, year = {2018}, author = {O'Connell, TC and Collins, MJ}, title = {Comment on "Ecological niche of Neanderthals from Spy Cave revealed by nitrogen isotopes of individual amino acids in collagen" [J. Hum. Evol. 93 (2016) 82-90].}, journal = {Journal of human evolution}, volume = {117}, number = {}, pages = {53-55}, doi = {10.1016/j.jhevol.2017.05.006}, pmid = {28602430}, issn = {1095-8606}, } @article {pmid28600395, year = {2018}, author = {Garcia, MA and Nelson, WJ and Chavez, N}, title = {Cell-Cell Junctions Organize Structural and Signaling Networks.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, pmid = {28600395}, issn = {1943-0264}, support = {R35 GM118064/GM/NIGMS NIH HHS/United States ; }, abstract = {Cell-cell junctions link cells to each other in tissues, and regulate tissue homeostasis in critical cell processes that include tissue barrier function, cell proliferation, and migration. Defects in cell-cell junctions give rise to a wide range of tissue abnormalities that disrupt homeostasis and are common in genetic abnormalities and cancers. Here, we discuss the organization and function of cell-cell junctions primarily involved in adhesion (tight junction, adherens junction, and desmosomes) in two different epithelial tissues: a simple epithelium (intestine) and a stratified epithelium (epidermis). Studies in these tissues reveal similarities and differences in the organization and functions of different cell-cell junctions that meet the requirements for the specialized functions of each tissue. We discuss cell-cell junction responses to genetic and environmental perturbations that provide further insights into their roles in maintaining tissue homeostasis.}, } @article {pmid28600394, year = {2018}, author = {Zinski, J and Tajer, B and Mullins, MC}, title = {TGF-β Family Signaling in Early Vertebrate Development.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {6}, pages = {}, doi = {10.1101/cshperspect.a033274}, pmid = {28600394}, issn = {1943-0264}, abstract = {TGF-β family ligands function in inducing and patterning many tissues of the early vertebrate embryonic body plan. Nodal signaling is essential for the specification of mesendodermal tissues and the concurrent cellular movements of gastrulation. Bone morphogenetic protein (BMP) signaling patterns tissues along the dorsal-ventral axis and simultaneously directs the cell movements of convergence and extension. After gastrulation, a second wave of Nodal signaling breaks the symmetry between the left and right sides of the embryo. During these processes, elaborate regulatory feedback between TGF-β ligands and their antagonists direct the proper specification and patterning of embryonic tissues. In this review, we summarize the current knowledge of the function and regulation of TGF-β family signaling in these processes. Although we cover principles that are involved in the development of all vertebrate embryos, we focus specifically on three popular model organisms: the mouse Mus musculus, the African clawed frog of the genus Xenopus, and the zebrafish Danio rerio, highlighting the similarities and differences between these species.}, } @article {pmid28600393, year = {2018}, author = {Karaman, R and Halder, G}, title = {Cell Junctions in Hippo Signaling.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a028753}, pmid = {28600393}, issn = {1943-0264}, abstract = {The Hippo signal transduction pathway is an important regulator of organ growth and cell differentiation, and its deregulation contributes to the development of cancer. The activity of the Hippo pathway is strongly dependent on cell junctions, cellular architecture, and the mechanical properties of the microenvironment. In this review, we discuss recent advances in our understanding of how cell junctions transduce signals from the microenvironment and control the activity of the Hippo pathway. We also discuss how these mechanisms may control organ growth during development and regeneration, and how defects in them deregulate Hippo signaling in cancer cells.}, } @article {pmid28598568, year = {2018}, author = {Perović, DJ and Gámez-Virués, S and Landis, DA and Wäckers, F and Gurr, GM and Wratten, SD and You, MS and Desneux, N}, title = {Managing biological control services through multi-trophic trait interactions: review and guidelines for implementation at local and landscape scales.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {306-321}, doi = {10.1111/brv.12346}, pmid = {28598568}, issn = {1469-185X}, abstract = {Ecological studies are increasingly moving towards trait-based approaches, as the evidence mounts that functions, as opposed to taxonomy, drive ecosystem service delivery. Among ecosystem services, biological control has been somewhat overlooked in functional ecological studies. This is surprising given that, over recent decades, much of biological control research has been focused on identifying the multiple characteristics (traits) of species that influence trophic interactions. These traits are especially well developed for interactions between arthropods and flowers - important for biological control, as floral resources can provide natural enemies with nutritional supplements, which can dramatically increase biological control efficiency. Traits that underpin the biological control potential of a community and that drive the response of arthropods to environmental filters, from local to landscape-level conditions, are also emerging from recent empirical studies. We present an overview of the traits that have been identified to (i) drive trophic interactions, especially between plants and biological control agents through determining access to floral resources and enhancing longevity and fecundity of natural enemies, (ii) affect the biological control services provided by arthropods, and (iii) limit the response of arthropods to environmental filters, ranging from local management practices to landscape-level simplification. We use this review as a platform to outline opportunities and guidelines for future trait-based studies focused on the enhancement of biological control services.}, } @article {pmid28593333, year = {2018}, author = {Di Donato, P and Romano, I and Mastascusa, V and Poli, A and Orlando, P and Pugliese, M and Nicolaus, B}, title = {Survival and Adaptation of the Thermophilic Species Geobacillus thermantarcticus in Simulated Spatial Conditions.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {141-158}, doi = {10.1007/s11084-017-9540-7}, pmid = {28593333}, issn = {1573-0875}, mesh = {*Desiccation ; Geobacillus/*physiology/radiation effects ; *Hot Temperature ; *Space Simulation ; *Ultraviolet Rays ; *X-Rays ; }, abstract = {Astrobiology studies the origin and evolution of life on Earth and in the universe. According to the panspermia theory, life on Earth could have emerged from bacterial species transported by meteorites, that were able to adapt and proliferate on our planet. Therefore, the study of extremophiles, i.e. bacterial species able to live in extreme terrestrial environments, can be relevant to Astrobiology studies. In this work we described the ability of the thermophilic species Geobacillus thermantarcticus to survive after exposition to simulated spatial conditions including temperature's variation, desiccation, X-rays and UVC irradiation. The response to the exposition to the space conditions was assessed at a molecular level by studying the changes in the morphology, the lipid and protein patterns, the nucleic acids. G. thermantarcticus survived to the exposition to all the stressing conditions examined, since it was able to restart cellular growth in comparable levels to control experiments carried out in the optimal growth conditions. Survival was elicited by changing proteins and lipids distribution, and by protecting the DNA's integrity.}, } @article {pmid28568902, year = {2018}, author = {Bonebrake, TC and Brown, CJ and Bell, JD and Blanchard, JL and Chauvenet, A and Champion, C and Chen, IC and Clark, TD and Colwell, RK and Danielsen, F and Dell, AI and Donelson, JM and Evengård, B and Ferrier, S and Frusher, S and Garcia, RA and Griffis, RB and Hobday, AJ and Jarzyna, MA and Lee, E and Lenoir, J and Linnetved, H and Martin, VY and McCormack, PC and McDonald, J and McDonald-Madden, E and Mitchell, N and Mustonen, T and Pandolfi, JM and Pettorelli, N and Possingham, H and Pulsifer, P and Reynolds, M and Scheffers, BR and Sorte, CJB and Strugnell, JM and Tuanmu, MN and Twiname, S and Vergés, A and Villanueva, C and Wapstra, E and Wernberg, T and Pecl, GT}, title = {Managing consequences of climate-driven species redistribution requires integration of ecology, conservation and social science.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {284-305}, doi = {10.1111/brv.12344}, pmid = {28568902}, issn = {1469-185X}, abstract = {Climate change is driving a pervasive global redistribution of the planet's species. Species redistribution poses new questions for the study of ecosystems, conservation science and human societies that require a coordinated and integrated approach. Here we review recent progress, key gaps and strategic directions in this nascent research area, emphasising emerging themes in species redistribution biology, the importance of understanding underlying drivers and the need to anticipate novel outcomes of changes in species ranges. We highlight that species redistribution has manifest implications across multiple temporal and spatial scales and from genes to ecosystems. Understanding range shifts from ecological, physiological, genetic and biogeographical perspectives is essential for informing changing paradigms in conservation science and for designing conservation strategies that incorporate changing population connectivity and advance adaptation to climate change. Species redistributions present challenges for human well-being, environmental management and sustainable development. By synthesising recent approaches, theories and tools, our review establishes an interdisciplinary foundation for the development of future research on species redistribution. Specifically, we demonstrate how ecological, conservation and social research on species redistribution can best be achieved by working across disciplinary boundaries to develop and implement solutions to climate change challenges. Future studies should therefore integrate existing and complementary scientific frameworks while incorporating social science and human-centred approaches. Finally, we emphasise that the best science will not be useful unless more scientists engage with managers, policy makers and the public to develop responsible and socially acceptable options for the global challenges arising from species redistributions.}, } @article {pmid28560765, year = {2018}, author = {Laurance, WF and Camargo, JLC and Fearnside, PM and Lovejoy, TE and Williamson, GB and Mesquita, RCG and Meyer, CFJ and Bobrowiec, PED and Laurance, SGW}, title = {An Amazonian rainforest and its fragments as a laboratory of global change.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {223-247}, doi = {10.1111/brv.12343}, pmid = {28560765}, issn = {1469-185X}, abstract = {We synthesize findings from one of the world's largest and longest-running experimental investigations, the Biological Dynamics of Forest Fragments Project (BDFFP). Spanning an area of ∼1000 km2 in central Amazonia, the BDFFP was initially designed to evaluate the effects of fragment area on rainforest biodiversity and ecological processes. However, over its 38-year history to date the project has far transcended its original mission, and now focuses more broadly on landscape dynamics, forest regeneration, regional- and global-change phenomena, and their potential interactions and implications for Amazonian forest conservation. The project has yielded a wealth of insights into the ecological and environmental changes in fragmented forests. For instance, many rainforest species are naturally rare and hence are either missing entirely from many fragments or so sparsely represented as to have little chance of long-term survival. Additionally, edge effects are a prominent driver of fragment dynamics, strongly affecting forest microclimate, tree mortality, carbon storage and a diversity of fauna. Even within our controlled study area, the landscape has been highly dynamic: for example, the matrix of vegetation surrounding fragments has changed markedly over time, succeeding from large cattle pastures or forest clearcuts to secondary regrowth forest. This, in turn, has influenced the dynamics of plant and animal communities and their trajectories of change over time. In general, fauna and flora have responded differently to fragmentation: the most locally extinction-prone animal species are those that have both large area requirements and low tolerance of the modified habitats surrounding fragments, whereas the most vulnerable plants are those that respond poorly to edge effects or chronic forest disturbances, and that rely on vulnerable animals for seed dispersal or pollination. Relative to intact forests, most fragments are hyperdynamic, with unstable or fluctuating populations of species in response to a variety of external vicissitudes. Rare weather events such as droughts, windstorms and floods have had strong impacts on fragments and left lasting legacies of change. Both forest fragments and the intact forests in our study area appear to be influenced by larger-scale environmental drivers operating at regional or global scales. These drivers are apparently increasing forest productivity and have led to concerted, widespread increases in forest dynamics and plant growth, shifts in tree-community composition, and increases in liana (woody vine) abundance. Such large-scale drivers are likely to interact synergistically with habitat fragmentation, exacerbating its effects for some species and ecological phenomena. Hence, the impacts of fragmentation on Amazonian biodiversity and ecosystem processes appear to be a consequence not only of local site features but also of broader changes occurring at landscape, regional and even global scales.}, } @article {pmid28560755, year = {2018}, author = {Laptikhovsky, V and Nikolaeva, S and Rogov, M}, title = {Cephalopod embryonic shells as a tool to reconstruct reproductive strategies in extinct taxa.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {270-283}, doi = {10.1111/brv.12341}, pmid = {28560755}, issn = {1469-185X}, abstract = {An exhaustive study of existing data on the relationship between egg size and maximum size of embryonic shells in 42 species of extant cephalopods demonstrated that these values are approximately equal regardless of taxonomy and shell morphology. Egg size is also approximately equal to mantle length of hatchlings in 45 cephalopod species with rudimentary shells. Paired data on the size of the initial chamber versus embryonic shell in 235 species of Ammonoidea, 46 Bactritida, 13 Nautilida, 22 Orthocerida, 8 Tarphycerida, 4 Oncocerida, 1 Belemnoidea, 4 Sepiida and 1 Spirulida demonstrated that, although there is a positive relationship between these parameters in some taxa, initial chamber size cannot be used to predict egg size in extinct cephalopods; the size of the embryonic shell may be more appropriate for this task. The evolution of reproductive strategies in cephalopods in the geological past was marked by an increasing significance of small-egged taxa, as is also seen in simultaneously evolving fish taxa.}, } @article {pmid28547852, year = {2018}, author = {Pérez-Manrique, A and Gomila, A}, title = {The comparative study of empathy: sympathetic concern and empathic perspective-taking in non-human animals.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {248-269}, doi = {10.1111/brv.12342}, pmid = {28547852}, issn = {1469-185X}, abstract = {While empathy is a century-old psychological concept, its study in non-human animals has become the focus of much recent scientific interest, as it promises to provide the clues to understand the evolutionary origins of our social and moral nature. A review of the comparative study of empathy is thus timely to complement and constrain anthropocentric views, and to integrate current findings. However, this is not an easy task. The study of animal empathy has developed using different paradigms, different concepts of the phenomena involved, and the absence of a systematic program. Herein, we carry out a comprehensive review of the literature on complex forms of empathy in non-human animals: sympathetic concern and empathic perspective-taking. In particular, we focus on consolation and targeted helping, as the best examples of each category. In so doing, we try to shed light on the current debate concerning whether these phenomena are exclusively human traits. First, we try to clarify the terminology and taxonomy of forms of empathy, providing operative criteria for these phenomena that are applicable to both human and non-human animals. Second, we discuss whether the available evidence qualifies such behaviour as empathic. Third, we aim to provide an integrative view of the field, clarifying the challenges and conditions to satisfy. We also hope to highlight the importance of the study of these processes for elucidating the evolutionary history of this capacity across the animal kingdom.}, } @article {pmid28544184, year = {2018}, author = {Bodył, A}, title = {Did some red alga-derived plastids evolve via kleptoplastidy? A hypothesis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {201-222}, doi = {10.1111/brv.12340}, pmid = {28544184}, issn = {1469-185X}, abstract = {The evolution of plastids has a complex and still unresolved history. These organelles originated from a cyanobacterium via primary endosymbiosis, resulting in three eukaryotic lineages: glaucophytes, red algae, and green plants. The red and green algal plastids then spread via eukaryote-eukaryote endosymbioses, known as secondary and tertiary symbioses, to numerous heterotrophic protist lineages. The number of these horizontal plastid transfers, especially in the case of red alga-derived plastids, remains controversial. Some authors argue that the number of plastid origins should be minimal due to perceived difficulties in the transformation of a eukaryotic algal endosymbiont into a multimembrane plastid, but increasingly the available data contradict this argument. I suggest that obstacles in solving this dilemma result from the acceptance of a single evolutionary scenario for the endosymbiont-to-plastid transformation formulated by Cavalier-Smith & Lee (1985). Herein I discuss data that challenge this evolutionary scenario. Moreover, I propose a new model for the origin of multimembrane plastids belonging to the red lineage and apply it to the dinoflagellate peridinin plastid. The new model has several general and practical implications, such as the requirement for a new definition of cell organelles and in the construction of chimeric organisms.}, } @article {pmid28508537, year = {2018}, author = {Boomsma, JJ and Gawne, R}, title = {Superorganismality and caste differentiation as points of no return: how the major evolutionary transitions were lost in translation.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {28-54}, doi = {10.1111/brv.12330}, pmid = {28508537}, issn = {1469-185X}, abstract = {More than a century ago, William Morton Wheeler proposed that social insect colonies can be regarded as superorganisms when they have morphologically differentiated reproductive and nursing castes that are analogous to the metazoan germ-line and soma. Following the rise of sociobiology in the 1970s, Wheeler's insights were largely neglected, and we were left with multiple new superorganism concepts that are mutually inconsistent and uninformative on how superorganismality originated. These difficulties can be traced to the broadened sociobiological concept of eusociality, which denies that physical queen-worker caste differentiation is a universal hallmark of superorganismal colonies. Unlike early evolutionary naturalists and geneticists such as Weismann, Huxley, Fisher and Haldane, who set out to explain the acquisition of an unmated worker caste, the goal of sociobiology was to understand the evolution of eusociality, a broad-brush convenience category that covers most forms of cooperative breeding. By lumping a diverse spectrum of social systems into a single category, and drawing attention away from the evolution of distinct quantifiable traits, the sociobiological tradition has impeded straightforward connections between inclusive fitness theory and the major evolutionary transitions paradigm for understanding irreversible shifts to higher organizational complexity. We evaluate the history by which these inconsistencies accumulated, develop a common-cause approach for understanding the origins of all major transitions in eukaryote hierarchical complexity, and use Hamilton's rule to argue that they are directly comparable. We show that only Wheeler's original definition of superorganismality can be unambiguously linked to irreversible evolutionary transitions from context-dependent reproductive altruism to unconditional differentiation of permanently unmated castes in the ants, corbiculate bees, vespine wasps and higher termites. We argue that strictly monogamous parents were a necessary, albeit not sufficient condition for all transitions to superorganismality, analogous to single-zygote bottlenecking being a necessary but not sufficient condition for the convergent origins of complex soma across multicellular eukaryotes. We infer that conflict reduction was not a necessary condition for the origin of any of these major transitions, and conclude that controversies over the status of inclusive fitness theory primarily emanate from the arbitrarily defined sociobiological concepts of superorganismality and eusociality, not from the theory itself.}, } @article {pmid28507022, year = {2018}, author = {Bruner, HC and Derksen, PWB}, title = {Loss of E-Cadherin-Dependent Cell-Cell Adhesion and the Development and Progression of Cancer.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a029330}, pmid = {28507022}, issn = {1943-0264}, abstract = {Classical cadherins are the key molecules that control cell-cell adhesion. Notwithstanding this function, it is also clear that classical cadherins are more than just the "glue" that keeps the cells together. Cadherins are essential regulators of tissue homeostasis that govern multiple facets of cellular function and development, by transducing adhesive signals to a complex network of signaling effectors and transcriptional programs. In cancer, cadherins are often inactivated or functionally inhibited, resulting in disease development and/or progression. This review focuses on E-cadherin and its causal role in the development and progression of breast and gastric cancer. We provide a summary of the biochemical consequences and consider the conceptual impact of early (mutational) E-cadherin loss in cancer. We advocate that carcinomas driven by E-cadherin loss should be considered "actin-diseases," caused by the specific disruption of the E-cadherin-actin connection and a subsequent dependence on sustained actomyosin contraction for tumor progression. Based on the available data from mouse and human studies we discuss opportunities for targeted clinical intervention.}, } @article {pmid28507021, year = {2018}, author = {Buckley, A and Turner, JR}, title = {Cell Biology of Tight Junction Barrier Regulation and Mucosal Disease.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, pmid = {28507021}, issn = {1943-0264}, support = {R01 DK061931/DK/NIDDK NIH HHS/United States ; R01 DK068271/DK/NIDDK NIH HHS/United States ; }, abstract = {Mucosal surfaces are lined by epithelial cells. In the intestine, the epithelium establishes a selectively permeable barrier that supports nutrient absorption and waste secretion while preventing intrusion by luminal materials. Intestinal epithelia therefore play a central role in regulating interactions between the mucosal immune system and luminal contents, which include dietary antigens, a diverse intestinal microbiome, and pathogens. The paracellular space is sealed by the tight junction, which is maintained by a complex network of protein interactions. Tight junction dysfunction has been linked to a variety of local and systemic diseases. Two molecularly and biophysically distinct pathways across the intestinal tight junction are selectively and differentially regulated by inflammatory stimuli. This review discusses the mechanisms underlying these events, their impact on disease, and the potential of using these as paradigms for development of tight junction-targeted therapeutic interventions.}, } @article {pmid28507020, year = {2018}, author = {Grafe, I and Alexander, S and Peterson, JR and Snider, TN and Levi, B and Lee, B and Mishina, Y}, title = {TGF-β Family Signaling in Mesenchymal Differentiation.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {5}, pages = {}, doi = {10.1101/cshperspect.a022202}, pmid = {28507020}, issn = {1943-0264}, abstract = {Mesenchymal stem cells (MSCs) can differentiate into several lineages during development and also contribute to tissue homeostasis and regeneration, although the requirements for both may be distinct. MSC lineage commitment and progression in differentiation are regulated by members of the transforming growth factor-β (TGF-β) family. This review focuses on the roles of TGF-β family signaling in mesenchymal lineage commitment and differentiation into osteoblasts, chondrocytes, myoblasts, adipocytes, and tenocytes. We summarize the reported findings of cell culture studies, animal models, and interactions with other signaling pathways and highlight how aberrations in TGF-β family signaling can drive human disease by affecting mesenchymal differentiation.}, } @article {pmid28484901, year = {2018}, author = {Furukawa, Y and Takase, A and Sekine, T and Kakegawa, T and Kobayashi, T}, title = {Racemization of Valine by Impact-Induced Heating.}, journal = {Origins of life and evolution of the biosphere : the journal of the International Society for the Study of the Origin of Life}, volume = {48}, number = {1}, pages = {131-139}, doi = {10.1007/s11084-017-9539-0}, pmid = {28484901}, issn = {1573-0875}, support = {24654176//Japan Society for the Promotion of Science/ ; 24244084//Japan Society for the Promotion of Science/ ; 23740402//Japan Society for the Promotion of Science/ ; }, mesh = {Calcium Carbonate/chemistry ; Evolution, Chemical ; Ferric Compounds/chemistry ; *Heating ; Iron Compounds/chemistry ; Magnesium Compounds/chemistry ; *Meteoroids ; Origin of Life ; Silicates/chemistry ; Stereoisomerism ; Valine/*chemistry ; }, abstract = {Homochirality plays an important role in all living organisms but its origin remains unclear. It also remains unclear whether such chiral molecules survived terrestrial heavy impact events. Impacts of extraterrestrial objects on early oceans were frequent and could have affected the chirality of oceanic amino acids when such amino acids accumulated during impacts. This study investigated the effects of shock-induced heating on enantiomeric change of valine with minerals such as olivine ([Mg0.9, Fe0.1]2SiO4), hematite (Fe2O3), and calcite (CaCO3). With a shock wave generated by an impact at ~0.8 km/s, both D- and L-enriched valine were significantly decomposed and partially racemized under all experimental conditions. Different minerals had different shock impedances; therefore, they provided different P-T conditions for identical impacts. Furthermore, the high pH of calcite promoted the racemization of valine. The results indicate that in natural hypervelocity impacts, amino acids in shocked oceanic water would have decomposed completely, since impact velocity and the duration of shock compression and heating are typically greater in hypervelocity impact events than those in experiments. Even with the shock wave by the impact of small and decelerated projectiles in which amino acids survive, the shock heating may generate sufficient heat for significant racemization in shocked oceanic water. However, the duration of shock induced heating by small projectiles is limited and the population of such decelerated projectiles would be limited. Therefore, even though impacts of asteroids and meteorites were frequent on the prebiotic Earth, impact events would not have significantly changed the ee of proteinogenic amino acids accumulated in the entire ocean.}, } @article {pmid28480618, year = {2018}, author = {Pelosi, P and Iovinella, I and Zhu, J and Wang, G and Dani, FR}, title = {Beyond chemoreception: diverse tasks of soluble olfactory proteins in insects.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {184-200}, doi = {10.1111/brv.12339}, pmid = {28480618}, issn = {1469-185X}, abstract = {Odorant-binding proteins (OBPs) and chemosensory proteins (CSPs) are regarded as carriers of pheromones and odorants in insect chemoreception. These proteins are typically located in antennae, mouth organs and other chemosensory structures; however, members of both classes of proteins have been detected recently in other parts of the body and various functions have been proposed. The best studied of these non-sensory tasks is performed in pheromone glands, where OBPs and CSPs solubilise hydrophobic semiochemicals and assist their controlled release into the environment. In some cases the same proteins are expressed in antennae and pheromone glands, thus performing a dual role in receiving and broadcasting the same chemical message. Several reports have described OBPs and CSPs in reproductive organs. Some of these proteins are male specific and are transferred to females during mating. They likely carry semiochemicals with different proposed roles, from inhibiting other males from approaching mated females, to marking fertilized eggs, but further experimental evidence is still needed. Before being discovered in insects, the presence of binding proteins in pheromone glands and reproductive organs was widely reported in mammals, where vertebrate OBPs, structurally different from OBPs of insects and belonging to the lipocalin superfamily, are abundant in rodent urine, pig saliva and vaginal discharge of the hamster, as well as in the seminal fluid of rabbits. In at least four cases CSPs have been reported to promote development and regeneration: in embryo maturation in the honeybee, limb regeneration in the cockroach, ecdysis in larvae of fire ants and in promoting phase shift in locusts. Both OBPs and CSPs are also important in nutrition as solubilisers of lipids and other essential components of the diet. Particularly interesting is the affinity for carotenoids of CSPs abundantly secreted in the proboscis of moths and butterflies and the occurrence of the same (or very similar CSPs) in the eyes of the same insects. A role as a carrier of visual pigments for these proteins in insects parallels that of retinol-binding protein in vertebrates, a lipocalin structurally related to OBPs of vertebrates. Other functions of OBPs and CSPs include anti-inflammatory action in haematophagous insects, resistance to insecticides and eggshell formation. Such multiplicity of roles and the high success of both classes of proteins in being adapted to different situations is likely related to their stable scaffolding determining excellent stability to temperature, proteolysis and denaturing agents. The wide versatility of both OBPs and CSPs in nature has suggested several different uses for these proteins in biotechnological applications, from biosensors for odours to scavengers for pollutants and controlled releasers of chemicals in the environment.}, } @article {pmid28476281, year = {2018}, author = {Walker, CS and Yapuncich, GS and Sridhar, S and Cameron, N and Churchill, SE}, title = {Evaluating morphometric body mass prediction equations with a juvenile human test sample: accuracy and applicability to small-bodied hominins.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {65-77}, doi = {10.1016/j.jhevol.2017.03.009}, pmid = {28476281}, issn = {1095-8606}, abstract = {Body mass is an ecologically and biomechanically important variable in the study of hominin biology. Regression equations derived from recent human samples allow for the reasonable prediction of body mass of later, more human-like, and generally larger hominins from hip joint dimensions, but potential differences in hip biomechanics across hominin taxa render their use questionable with some earlier taxa (i.e., Australopithecus spp.). Morphometric prediction equations using stature and bi-iliac breadth avoid this problem, but their applicability to early hominins, some of which differ in both size and proportions from modern adult humans, has not been demonstrated. Here we use mean stature, bi-iliac breadth, and body mass from a global sample of human juveniles ranging in age from 6 to 12 years (n = 530 age- and sex-specific group annual means from 33 countries/regions) to evaluate the accuracy of several published morphometric prediction equations when applied to small humans. Though the body proportions of modern human juveniles likely differ from those of small-bodied early hominins, human juveniles (like fossil hominins) often differ in size and proportions from adult human reference samples and, accordingly, serve as a useful model for assessing the robustness of morphometric prediction equations. Morphometric equations based on adults systematically underpredict body mass in the youngest age groups and moderately overpredict body mass in the older groups, which fall in the body size range of adult Australopithecus (∼26-46 kg). Differences in body proportions, notably the ratio of lower limb length to stature, influence predictive accuracy. Ontogenetic changes in these body proportions likely influence the shift in prediction error (from under- to overprediction). However, because morphometric equations are reasonably accurate when applied to this juvenile test sample, we argue these equations may be used to predict body mass in small-bodied hominins, despite the potential for some error induced by differing body proportions and/or extrapolation beyond the original reference sample range.}, } @article {pmid28476280, year = {2018}, author = {Yapuncich, GS}, title = {Alternative methods for calculating percentage prediction error and their implications for predicting body mass in fossil taxa.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {140-145}, doi = {10.1016/j.jhevol.2017.03.001}, pmid = {28476280}, issn = {1095-8606}, abstract = {Since body mass covaries with many ecological aspects of an animal, body mass prediction of fossil taxa is a frequent goal of paleontologists. Body mass prediction often relies on a body mass prediction equation (BMPE): a bivariate relationship between a predictor variable (e.g., molar occlusal area, femoral head breadth) and body mass as observed in extant taxa. A variety of metrics have been used to assess the reliability of BMPEs, including percentage prediction error (%PE), which involves predicting body masses of a test sample comprising individuals with associated masses. A mean %PE can be calculated in two ways: 1) as the mean %PE of multiple individual predictions (%MPE), or 2) as the %PE of mean body mass generated from the mean predictor value of multiple individuals (here termed %PEM). Differences between these two approaches have never been formally examined and no formal protocols have been recommended. Using a large sample of cercopithecoid primates (406 individuals from 50 species/subspecies) with associated body masses, body mass is predicted with six previously published interspecific BMPEs. Both %MPE and %PEM are calculated and compared. For all BMPEs, the distributions of differences between %MPE and %PEM exhibit positive skew and have medians significantly greater than zero, indicating that the examined prediction equations are more accurate at predicting mean body mass when they are applied to mean predictor values. The decreased predictive accuracy of %MPE relative to %PEM likely stems from changing the unit of analysis from mean values (in the reference sample) to individual values (in the test sample) when calculating %MPE. Empirical results are supported with a simulated dataset. Implications for body mass prediction in fossil species are discussed.}, } @article {pmid28474820, year = {2018}, author = {Ellegaard, M and Ribeiro, S}, title = {The long-term persistence of phytoplankton resting stages in aquatic 'seed banks'.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {166-183}, doi = {10.1111/brv.12338}, pmid = {28474820}, issn = {1469-185X}, abstract = {In the past decade, research on long-term persistence of phytoplankton resting stages has intensified. Simultaneously, insight into life-cycle variability in the diverse groups of phytoplankton has also increased. Aquatic 'seed banks' have tremendous significance and show many interesting parallels to terrestrial seed beds of vascular plants, but are much less studied. It is therefore timely to review the phenomenon of long-term persistence of aquatic resting stages in sediment seed banks. Herein we compare function, morphology and physiology of phytoplankton resting stages to factors central for persistence of terrestrial seeds. We review the types of resting stages found in different groups of phytoplankton and focus on the groups for which long-term (multi-decadal) persistence has been shown: dinoflagellates, diatoms, green algae and cyanobacteria. We discuss the metabolism of long-term dormancy in phytoplankton resting stages and the ecological, evolutionary and management implications of this important trait. Phytoplankton resting stages exhibiting long-term viability are characterized by thick, often multi-layered walls and accumulation vesicles containing starch, lipids or other materials such as pigments, cyanophycin or unidentified granular materials. They are reported to play central roles in evolutionary resilience and survival of catastrophic events. Promising areas for future research include the role of hormones in mediating dormancy, elucidating the mechanisms behind metabolic shut-down and testing bet-hedging hypotheses.}, } @article {pmid28464469, year = {2018}, author = {Floeter, SR and Bender, MG and Siqueira, AC and Cowman, PF}, title = {Phylogenetic perspectives on reef fish functional traits.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {131-151}, doi = {10.1111/brv.12336}, pmid = {28464469}, issn = {1469-185X}, abstract = {Functional traits have been fundamental to the evolution and diversification of entire fish lineages on coral reefs. Yet their relationship with the processes promoting speciation, extinction and the filtering of local species pools remains unclear. We review the current literature exploring the evolution of diet, body size, water column use and geographic range size in reef-associated fishes. Using published and new data, we mapped functional traits on to published phylogenetic trees to uncover evolutionary patterns that have led to the current functional diversity of fishes on coral reefs. When examining reconstructed patterns for diet and feeding mode, we found examples of independent transitions to planktivory across different reef fish families. Such transitions and associated morphological alterations may represent cases in which ecological opportunity for the exploitation of different resources drives speciation and adaptation. In terms of body size, reconstructions showed that both large and small sizes appear multiple times within clades of mid-sized fishes and that extreme body sizes have arisen mostly in the last 10 million years (Myr). The reconstruction of range size revealed many cases of disparate range sizes among sister species. Such range size disparity highlights potential vicariant processes through isolation in peripheral locations. When accounting for peripheral speciation processes in sister pairs, we found a significant relationship between labrid range size and lineage age. The diversity and evolution of traits within lineages is influenced by trait-environment interactions as well as by species and trait-trait interactions, where the presence of a given trait may trigger the development of related traits or behaviours. Our effort to assess the evolution of functional diversity across reef fish clades adds to the burgeoning research focusing on the evolutionary and ecological roles of functional traits. We argue that the combination of a phylogenetic and a functional approach will improve the understanding of the mechanisms of species assembly in extraordinarily rich coral reef communities.}, } @article {pmid28464404, year = {2018}, author = {Lorente, J and Velandia, C and Leal, JA and Garcia-Mayea, Y and Lyakhovich, A and Kondoh, H and LLeonart, ME}, title = {The interplay between autophagy and tumorigenesis: exploiting autophagy as a means of anticancer therapy.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {152-165}, doi = {10.1111/brv.12337}, pmid = {28464404}, issn = {1469-185X}, abstract = {In wild-type cells, autophagy represents a tumour-suppressor mechanism, and dysfunction of the autophagy machinery increases genomic instability, DNA damage, oxidative stress and stem/progenitor expansion, which are events associated with cancer onset. Autophagy occurs at a basal level in all cells depending on cell type and cellular microenvironment. However, the role of autophagy in cancer is diverse and can promote different outcomes even in a single tumour. For example, in hypoxic tumour regions, autophagy emerges as a protective mechanism and allows cancer cell survival. By contrast, in cancer cells surrounding the tumour mass, the induction of autophagy by radio- or chemotherapy promotes cell death and significantly reduces the tumour mass. Importantly, inhibition of autophagy compromises tumorigenesis by mechanisms that are not entirely understood. The aim of this review is to explain the apparently contradictory role of autophagy as a mechanism that both promotes and inhibits tumorigenesis using different models. The induction/inhibition of autophagy as a mechanism for cancer treatment is also discussed.}, } @article {pmid28464349, year = {2018}, author = {Noble, DWA and Stenhouse, V and Schwanz, LE}, title = {Developmental temperatures and phenotypic plasticity in reptiles: a systematic review and meta-analysis.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {72-97}, doi = {10.1111/brv.12333}, pmid = {28464349}, issn = {1469-185X}, abstract = {Early environments can profoundly influence an organism in ways that persist over its life. In reptiles, early thermal environments (nest temperatures) can impact offspring phenotype and survival in important ways, yet we still lack an understanding of whether general trends exist and the magnitude of impact. Understanding these patterns is important in predicting how climate change will affect reptile populations and the role of phenotypic plasticity in buffering populations. We compiled data from 175 reptile studies to examine, and quantify, the effect of incubation temperature on phenotype and survival. Using meta-analytic approaches (standardized mean difference between incubation treatments, Hedges' g), we show that across all trait types examined there is, on average, a moderate to large magnitude of effect of incubation temperatures (absolute effect: |g| = 0.75). Unsurprisingly, this influence was extremely large for incubation duration, as predicted, with warmer temperatures decreasing incubation time overall (g = -8.42). Other trait types, including behaviour, physiology, morphology, performance, and survival experienced reduced, but still mostly moderate to large effects, with particularly strong effects on survival. Moreover, the impact of incubation temperature persisted at least one-year post-hatching, suggesting that these effects have the potential to impact fitness in the long term. The magnitude of effect increased as the change in temperature increased (e.g. 6°C versus 2°C) in almost all cases, and tended to decrease when temperatures of the treatments fluctuated around a mean temperature compared to when they were constant. The effect also depended on the mid-temperature of the comparison, but not in consistent ways, with some traits experiencing the greatest effects at extreme temperatures, while others did not. The highly heterogeneous nature of the effects we observe, along with a large amount of unexplained variability, indicates that the shape of reaction norms between phenotype and temperature, along with ecological and/or experimental factors, are important when considering general patterns. Our analyses provide new insights into the effects of incubation environments on reptile phenotype and survival and allow general, albeit coarse, predictions for taxa experiencing warming nest temperatures under climatic change.}, } @article {pmid28447398, year = {2018}, author = {Schmeller, DS and Weatherdon, LV and Loyau, A and Bondeau, A and Brotons, L and Brummitt, N and Geijzendorffer, IR and Haase, P and Kuemmerlen, M and Martin, CS and Mihoub, JB and Rocchini, D and Saarenmaa, H and Stoll, S and Regan, EC}, title = {A suite of essential biodiversity variables for detecting critical biodiversity change.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {55-71}, doi = {10.1111/brv.12332}, pmid = {28447398}, issn = {1469-185X}, abstract = {Key global indicators of biodiversity decline, such as the IUCN Red List Index and the Living Planet Index, have relatively long assessment intervals. This means they, due to their inherent structure, function as late-warning indicators that are retrospective, rather than prospective. These indicators are unquestionably important in providing information for biodiversity conservation, but the detection of early-warning signs of critical biodiversity change is also needed so that proactive management responses can be enacted promptly where required. Generally, biodiversity conservation has dealt poorly with the scattered distribution of necessary detailed information, and needs to find a solution to assemble, harmonize and standardize the data. The prospect of monitoring essential biodiversity variables (EBVs) has been suggested in response to this challenge. The concept has generated much attention, but the EBVs themselves are still in development due to the complexity of the task, the limited resources available, and a lack of long-term commitment to maintain EBV data sets. As a first step, the scientific community and the policy sphere should agree on a set of priority candidate EBVs to be developed within the coming years to advance both large-scale ecological research as well as global and regional biodiversity conservation. Critical ecological transitions are of high importance from both a scientific as well as from a conservation policy point of view, as they can lead to long-lasting biodiversity change with a high potential for deleterious effects on whole ecosystems and therefore also on human well-being. We evaluated candidate EBVs using six criteria: relevance, sensitivity to change, generalizability, scalability, feasibility, and data availability and provide a literature-based review for eight EBVs with high sensitivity to change. The proposed suite of EBVs comprises abundance, allelic diversity, body mass index, ecosystem heterogeneity, phenology, range dynamics, size at first reproduction, and survival rates. The eight candidate EBVs provide for the early detection of critical and potentially long-lasting biodiversity change and should be operationalized as a priority. Only with such an approach can science predict the future status of global biodiversity with high certainty and set up the appropriate conservation measures early and efficiently. Importantly, the selected EBVs would address a large range of conservation issues and contribute to a total of 15 of the 20 Aichi targets and are, hence, of high biological relevance.}, } @article {pmid28444848, year = {2018}, author = {Parsons, MH and Apfelbach, R and Banks, PB and Cameron, EZ and Dickman, CR and Frank, ASK and Jones, ME and McGregor, IS and McLean, S and Müller-Schwarze, D and Sparrow, EE and Blumstein, DT}, title = {Biologically meaningful scents: a framework for understanding predator-prey research across disciplines.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {98-114}, doi = {10.1111/brv.12334}, pmid = {28444848}, issn = {1469-185X}, abstract = {Fear of predation is a universal motivator. Because predators hunt using stealth and surprise, there is a widespread ability among prey to assess risk from chemical information - scents - in their environment. Consequently, scents often act as particularly strong modulators of memory and emotions. Recent advances in ecological research and analytical technology are leading to novel ways to use this chemical information to create effective attractants, repellents and anti-anxiolytic compounds for wildlife managers, conservation biologists and health practitioners. However, there is extensive variation in the design, results, and interpretation of studies of olfactory-based risk discrimination. To understand the highly variable literature in this area, we adopt a multi-disciplinary approach and synthesize the latest findings from neurobiology, chemical ecology, and ethology to propose a contemporary framework that accounts for such disparate factors as the time-limited stability of chemicals, highly canalized mechanisms that influence prey responses, and the context within which these scents are detected (e.g. availability of alternative resources, perceived shelter, and ambient physical parameters). This framework helps to account for the wide range of reported responses by prey to predator scents, and explains, paradoxically, how the same individual predator scent can be interpreted as either safe or dangerous to a prey animal depending on how, when and where the cue was deposited. We provide a hypothetical example to illustrate the most common factors that influence how a predator scent (from dingoes, Canis dingo) may both attract and repel the same target organism (kangaroos, Macropus spp.). This framework identifies the catalysts that enable dynamic scents, odours or odorants to be used as attractants as well as deterrents. Because effective scent tools often relate to traumatic memories (fear and/or anxiety) that cause future avoidance, this information may also guide the development of appeasement, enrichment and anti-anxiolytic compounds, and help explain the observed variation in post-traumatic-related behaviours (including post-traumatic stress disorder, PTSD) among diverse terrestrial taxa, including humans.}, } @article {pmid29904561, year = {2018}, author = {Cleveland, LM and McCabe, TM and Olimpo, JT}, title = {A Call for Programmatic Assessment of Undergraduate Students' Conceptual Understanding and Higher-Order Cognitive Skills.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904561}, issn = {1935-7877}, abstract = {In response to empirical evidence and calls for change, individual undergraduate biology instructors are reforming their pedagogical practices. To assess the effectiveness of these reforms, many instructors use course-specific or skill-specific assessments (e.g., concept inventories). We commend our colleagues' noble efforts, yet we contend that this is only a starting point. In this Perspectives article, we argue that departments need to engage in reform and programmatic assessment to produce graduates who have both subject-matter knowledge and higher-order cognitive skills. We encourage biology education researchers to work collaboratively with content specialists to develop program-level assessments aimed at measuring students' conceptual understanding and higher-order cognitive skills, and we encourage departments to develop longitudinal plans for monitoring their students' development of these skills.}, } @article {pmid28433248, year = {2018}, author = {Sharma, PP and Oberski, JT and Santiago, MA and Kriebel, R and Lipps, SM and Buenavente, PAC and Diesmos, AC and Janda, M and Boyer, SL and Clouse, RM and Wheeler, WC}, title = {There is no evidence that Podoctidae carry eggs of their own species: Reply to Machado and Wolff (2017).}, journal = {Molecular phylogenetics and evolution}, volume = {129}, number = {}, pages = {349-353}, doi = {10.1016/j.ympev.2017.03.026}, pmid = {28433248}, issn = {1095-9513}, abstract = {In our recent publication (Sharma et al., 2017), we tested the hypothesis that eggs attached to the legs of male Podoctidae (Opiliones, Laniatores) constituted a case of paternal care, using molecular sequence data in tandem with multiple sequence alignments to test the prediction that sequences of the eggs and the adults that carried them would indicate conspecific identity. We discovered that the sequences of the eggs belonged to spiders, and thus rejected the paternal care hypothesis for these species. Machado and Wolff (2017) recently critiqued our work, which they regarded as a non-critical interpretation and over-reliance on molecular sequence data, and defended the traditional argument that the eggs attached to podoctids are in fact harvestman eggs. Here we show that additional molecular sequence data also refute the identity of the eggs as conspecific harvestman eggs, using molecular cloning techniques to rule out contamination. We show that individual gene trees consistently and reliably place the egg and adult sequences in disparate parts of the tree topology. Phylogenetic methods consistently place all egg sequences within the order Araneae (spiders). We submit that evidence for the paternal care hypothesis based on behavioral, morphological, and natural history approaches is either absent or insufficient for concluding that the eggs of podoctids are conspecific.}, } @article {pmid28432134, year = {2018}, author = {Kim, KK and Sheppard, D and Chapman, HA}, title = {TGF-β1 Signaling and Tissue Fibrosis.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, doi = {10.1101/cshperspect.a022293}, pmid = {28432134}, issn = {1943-0264}, support = {R01 HL044712/HL/NHLBI NIH HHS/United States ; R01 HL108904/HL/NHLBI NIH HHS/United States ; }, abstract = {Activation of TGF-β1 initiates a program of temporary collagen accumulation important to wound repair in many organs. However, the outcome of temporary extracellular matrix strengthening all too frequently morphs into progressive fibrosis, contributing to morbidity and mortality worldwide. To avoid this maladaptive outcome, TGF-β1 signaling is regulated at numerous levels and intimately connected to feedback signals that limit accumulation. Here, we examine the current understanding of the core functions of TGF-β1 in promoting collagen accumulation, parallel pathways that promote physiological repair, and pathological triggers that tip the balance toward progressive fibrosis. Implicit in better understanding of these processes is the identification of therapeutic opportunities that will need to be further advanced to limit or reverse organ fibrosis.}, } @article {pmid28432133, year = {2018}, author = {Sallusto, F and Cassotta, A and Hoces, D and Foglierini, M and Lanzavecchia, A}, title = {Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate Commitment? T-Cell Heterogeneity, Plasticity, and Selection in Humans.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a029421}, pmid = {28432133}, issn = {1943-0264}, abstract = {The wide range of effector and memory T cells is instrumental for immune regulation and tailored mechanisms of protection against pathogens. Here, we will focus on human CD4 T cells and discuss T-cell plasticity and intraclonal diversification in the context of a progressive and selective model of CD4 T-cell differentiation.}, } @article {pmid28432132, year = {2018}, author = {Johnson, JL and Vahedi, G}, title = {Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate Commitment? Epigenome: A Dynamic Vehicle for Transmitting and Recording Cytokine Signaling.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a028779}, pmid = {28432132}, issn = {1943-0264}, support = {K22 AI112570/AI/NIAID NIH HHS/United States ; }, abstract = {CD4+ T cells are critical for the elimination of an immense array of microbial pathogens. Although there are aspects of helper T-cell differentiation that can be modeled as a classic cell-fate commitment, CD4+ T cells also maintain considerable flexibility in their transcriptional program. Here, we present an overview of chromatin biology during cellular reprogramming and, within this context, envision how the scope of cellular reprogramming may be expanded to further our understanding of the controversy surrounding CD4+ T lymphocyte plasticity or determinism.}, } @article {pmid28432131, year = {2018}, author = {Littman, DR}, title = {Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens? If So, Is There Potential for Efficacious Microbiota-Based Vaccines?.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a029355}, pmid = {28432131}, issn = {1943-0264}, abstract = {The gut-resident constituents of the microbiota protect the mucosa from invasive pathogens through engagement of both innate and adaptive branches of the immune system. They are also likely to provide systemic protection from pathogens, by enhancing host robustness and tolerance to the invasive microbes and by inducing immune responses that prevent their growth. These properties of commensal microbiota, particularly the capacity of some bacteria to induce diverse types of antigen-specific immune responses, raises the prospect that they could be deployed as vaccine vectors to generate effective local and systemic immunity to viral and bacterial pathogens.}, } @article {pmid28432130, year = {2018}, author = {Collins, N and Belkaid, Y}, title = {Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens? Engaging Our Endogenous Adjuvants.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a028860}, pmid = {28432130}, issn = {1943-0264}, abstract = {The reliance of the immune system on constitutive microbial stimulation support the idea that both responsiveness to vaccines and vaccine design need to be considered in the context of host-microbiota interactions. Manipulation of microbe function or composition via diet alteration or microbiota engraftment may soon become a viable approach to control immunity and, as such, vaccine responses. Learning from our endogenous original adjuvants could be critical in overcoming the enormous hurdle of vaccine design against the numerous pathogens that cause chronic infection. Going forward, rationally designed vaccines that take advantage of the inherent adjuvant properties of the microbiota could have a major impact on the prevention of disease.}, } @article {pmid28432129, year = {2018}, author = {Crotty, S}, title = {Do Memory CD4 T Cells Keep Their Cell-Type Programming: Plasticity versus Fate Commitment? Complexities of Interpretation due to the Heterogeneity of Memory CD4 T Cells, Including T Follicular Helper Cells.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a032102}, pmid = {28432129}, issn = {1943-0264}, support = {UM1 AI100663/AI/NIAID NIH HHS/United States ; }, abstract = {Plasticity is the ability of a cell type to convert to another cell type. There are multiple effector CD4 T-cell subtypes, including TH1, TH2, TH17, TH1*, CD4 CTL, TH9, and TFH cells. It is commonly thought that a CD4 T cell can readily show full plasticity-full conversion from one differentiated cell-and this propensity to plasticity is possessed by memory CD4 T cells. However, there remains no direct demonstration of in vivo-generated resting memory CD4 T-cell conversion to a different subtype on secondary antigen challenge in vivo in an intact animal at the single-cell level. What has been clearly shown is that CD4 T cells possess extraordinary capacity for phenotypic heterogeneity, but that is a distinct property from plasticity. Heterogeneity is diversity of the resting memory CD4 T-cell population, not conversion of a single differentiated cell into another subtype. Apparently, plasticity at the population level can be accomplished by either mechanism, as heterogeneity of CD4 T-cell subpopulations could affect large shifts in subtype distribution at the overall population level via differential exponential expansion and death.}, } @article {pmid28432128, year = {2018}, author = {Macpherson, AJ}, title = {Do the Microbiota Influence Vaccines and Protective Immunity to Pathogens? Issues of Sovereignty, Federalism, and Points-Testing in the Prokaryotic and Eukaryotic Spaces of the Host-Microbial Superorganism.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a029363}, pmid = {28432128}, issn = {1943-0264}, abstract = {In contrast to live attenuated vaccines, which are designed to induce immunity through a time-limited bloom in systemic tissues, the microbiota is a persistent feature of body surfaces, especially the intestine. The immune responses to the microbiota are idiosyncratic depending on the niche intimacy of different taxa and generally adapt the host to avoid overgrowth and maintain mutualism rather than to eliminate the organisms of that taxon. Both the microbiota and the host have so much molecular cross talk controlling each other, that the prokaryotic and the eukaryotic spaces of the host-microbial superorganism are federal rather than sovereign. This molecular cross talk is vital for the immune system to develop its mature form. Nevertheless, the microbiota/host biomass spaces are rather well separated: The microbiota also limits colonization and penetration of pathogens through intense metabolic competition. Immune responses to those members of the microbiota mutually adapted to intimate association at mucosal surfaces have attractive potential durability, but for clinical use as persistent vehicles they would require personalization and engineered reversibility to manage the immune context and complications in individual human subjects.}, } @article {pmid28429851, year = {2018}, author = {Gippoliti, S and Cotterill, FPD and Zinner, D and Groves, CP}, title = {Impacts of taxonomic inertia for the conservation of African ungulate diversity: an overview.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {115-130}, doi = {10.1111/brv.12335}, pmid = {28429851}, issn = {1469-185X}, abstract = {We review the state of African ungulate taxonomy over the last 120 years, with an emphasis on the introduction of the polytypic species concept and the discipline's general neglect since the middle of the 20th century. We single out negative consequences of 'orthodox' taxonomy, highlighting numerous cases of neglect of threatened lineages, unsound translocations that led to lineage introgression, and cases of maladaptation to local conditions including parasitic infections. Additionally, several captive breeding programmes have been hampered by chromosome rearrangements caused by involuntary lineage mixing. We advocate that specimen-based taxonomy should regain its keystone role in mammal research and conservation biology, with its scientific values augmented with genomic evidence. While integration with molecular biology, ecology and behaviour is needed for a full understanding of ungulate alpha diversity, we stress that morphological diversity has been neglected despite its tremendous practical importance for some groups of 'utilizers' such as trophy hunters, wildlife tourists and conservationists. We conclude that there is no evidence that purported 'taxonomic inflation' has adverse effects on ungulate conservation: rather, it is taxonomic inertia that has such adverse effects. We stress that sound science, founded on robust taxonomy, should underpin effective sustainable management (hunting, ranching, captive breeding and reintroduction programmes) of this unique African natural resource.}, } @article {pmid28393457, year = {2018}, author = {Ronget, V and Gaillard, JM and Coulson, T and Garratt, M and Gueyffier, F and Lega, JC and Lemaître, JF}, title = {Causes and consequences of variation in offspring body mass: meta-analyses in birds and mammals.}, journal = {Biological reviews of the Cambridge Philosophical Society}, volume = {93}, number = {1}, pages = {1-27}, doi = {10.1111/brv.12329}, pmid = {28393457}, issn = {1469-185X}, abstract = {Early survival is highly variable and strongly influences observed population growth rates in most vertebrate populations. One of the major potential drivers of survival variation among juveniles is body mass. Heavy juveniles are better fed and have greater body reserves, and are thus assumed to survive better than light individuals. In spite of this, some studies have failed to detect an influence of body mass on offspring survival, questioning whether offspring body mass does indeed consistently influence juvenile survival, or whether this occurs in particular species/environments. Furthermore, the causes for variation in offspring mass are poorly understood, although maternal mass has often been reported to play a crucial role. To understand why offspring differ in body mass, and how this influences juvenile survival, we performed phylogenetically corrected meta-analyses of both the relationship between offspring body mass and offspring survival in birds and mammals and the relationship between maternal mass and offspring mass in mammals. We found strong support for an overall positive effect of offspring body mass on survival, with a more pronounced influence in mammals than in birds. An increase of one standard deviation of body mass increased the odds of offspring survival by 71% in mammals and by 44% in birds. A cost of being too fat in birds in terms of flight performance might explain why body mass is a less reliable predictor of offspring survival in birds. We then looked for moderators explaining the among-study differences reported in the intensity of this relationship. Surprisingly, sex did not influence the intensity of the offspring mass-survival relationship and phylogeny only accounted for a small proportion of observed variation in the intensity of that relationship. Among the potential factors that might affect the relationship between mass and survival in juveniles, only environmental conditions was influential in mammals. Offspring survival was most strongly influenced by body mass in captive populations and wild populations in the absence of predation. We also found support for the expected positive effect of maternal mass on offspring mass in mammals (rpearson = 0.387). As body mass is a strong predictor of early survival, we expected heavier mothers to allocate more to their offspring, leading them to be heavier and so to have a higher survival. However, none of the potential factors we tested for variation in the maternal mass-offspring mass relationship had a detectable influence. Further studies should focus on linking these two relationships to determine whether a strong effect of offspring size on early survival is associated with a high correlation coefficient between maternal mass and offspring mass.}, } @article {pmid28389444, year = {2018}, author = {Lowery, JW and Rosen, V}, title = {Bone Morphogenetic Protein-Based Therapeutic Approaches.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, doi = {10.1101/cshperspect.a022327}, pmid = {28389444}, issn = {1943-0264}, abstract = {Bone morphogenetic proteins (BMPs) constitute the largest subdivision of the transforming growth factor (TGF)-β family of ligands and exert most of their effects through the canonical effectors Smad1, 5, and 8. Appropriate regulation of BMP signaling is critical for the development and homeostasis of numerous human organ systems. Aberrations in BMP pathways or their regulation are increasingly associated with diverse human pathologies, and there is an urgent and growing need to develop effective approaches to modulate BMP signaling in the clinic. In this review, we provide a wide perspective on diseases and/or conditions associated with dysregulated BMP signal transduction, outline the current strategies available to modulate BMP pathways, highlight emerging second-generation technologies, and postulate prospective avenues for future investigation.}, } @article {pmid28348039, year = {2018}, author = {Jameson, SC and Masopust, D}, title = {What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Reevaluating the Potential of Mouse Models for the Human Immune System.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, doi = {10.1101/cshperspect.a029132}, pmid = {28348039}, issn = {1943-0264}, abstract = {Much of what we understand about immunology, including the response to vaccines, come from studies in mice because they provide many practical advantages compared with research in higher mammals and humans. Nevertheless, modalities for preventing or treating disease do not always translate from mouse to humans, which has led to increasing scrutiny of the continued merits of mouse research. Here, we summarize the pros and cons of current laboratory mouse models for immunology research and discuss whether overreliance on nonphysiological, ultra-hygienic animal husbandry approaches has limited the ultimate translation potential of mouse-derived data to humans. Alternative approaches are discussed that may extend the use of the mouse model for preclinical studies.}, } @article {pmid28348038, year = {2018}, author = {Goumans, MJ and Zwijsen, A and Ten Dijke, P and Bailly, S}, title = {Bone Morphogenetic Proteins in Vascular Homeostasis and Disease.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a031989}, pmid = {28348038}, issn = {1943-0264}, abstract = {It is well established that control of vascular morphogenesis and homeostasis is regulated by vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), Delta-like 4 (Dll4), angiopoietin, and ephrin signaling. It has become clear that signaling by bone morphogenetic proteins (BMPs), which have a long history of studies in bone and early heart development, are also essential for regulating vascular function. Indeed, mutations that cause deregulated BMP signaling are linked to two human vascular diseases, hereditary hemorrhagic telangiectasia and pulmonary arterial hypertension. These observations are corroborated by data obtained with vascular cells in cell culture and in mouse models. BMPs are required for normal endothelial cell differentiation and for venous/arterial and lymphatic specification. In adult life, BMP signaling orchestrates neo-angiogenesis as well as vascular inflammation, remodeling, and calcification responses to shear and oxidative stress. This review emphasizes the pivotal role of BMPs in the vascular system, based on studies of mouse models and human vascular disorders.}, } @article {pmid28348037, year = {2018}, author = {Herati, RS and Wherry, EJ}, title = {What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Consideration of Strategies to Improve the Value of Animal Models.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, doi = {10.1101/cshperspect.a031583}, pmid = {28348037}, issn = {1943-0264}, abstract = {Animal models are an essential feature of the vaccine design toolkit. Although animal models have been invaluable in delineating the mechanisms of immune function, their precision in predicting how well specific vaccines work in humans is often suboptimal. There are, of course, many obvious species differences that may limit animal models from predicting all details of how a vaccine works in humans. However, careful consideration of which animal models may have limitations should also allow more accurate interpretations of animal model data and more accurate predictions of what is to be expected in clinical trials. In this article, we examine some of the considerations that might be relevant to cross-species extrapolation of vaccine-related immune responses for the prediction of how vaccines will perform in humans.}, } @article {pmid28348036, year = {2018}, author = {Goumans, MJ and Ten Dijke, P}, title = {TGF-β Signaling in Control of Cardiovascular Function.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a022210}, pmid = {28348036}, issn = {1943-0264}, abstract = {Genetic studies in animals and humans indicate that gene mutations that functionally perturb transforming growth factor β (TGF-β) signaling are linked to specific hereditary vascular syndromes, including Osler-Rendu-Weber disease or hereditary hemorrhagic telangiectasia and Marfan syndrome. Disturbed TGF-β signaling can also cause nonhereditary disorders like atherosclerosis and cardiac fibrosis. Accordingly, cell culture studies using endothelial cells or smooth muscle cells (SMCs), cultured alone or together in two- or three-dimensional cell culture assays, on plastic or embedded in matrix, have shown that TGF-β has a pivotal effect on endothelial and SMC proliferation, differentiation, migration, tube formation, and sprouting. Moreover, TGF-β can stimulate endothelial-to-mesenchymal transition, a process shown to be of key importance in heart valve cushion formation and in various pathological vascular processes. Here, we discuss the roles of TGF-β in vasculogenesis, angiogenesis, and lymphangiogenesis and the deregulation of TGF-β signaling in cardiovascular diseases.}, } @article {pmid28348035, year = {2018}, author = {Golding, H and Khurana, S and Zaitseva, M}, title = {What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? The Importance of Bridging Studies and Species-Independent Correlates of Protection.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, doi = {10.1101/cshperspect.a028902}, pmid = {28348035}, issn = {1943-0264}, abstract = {Animal models have played a pivotal role in all stages of vaccine development. Their predictive value for vaccine effectiveness depends on the pathogen, the robustness of the animal challenge model, and the correlates of protection (if known). This article will cover key questions regarding bridging animal studies to efficacy trials in humans. Examples include human papillomavirus (HPV) vaccine in which animal protection after vaccination with heterologous prototype virus-like particles (VLPs) predicted successful efficacy trials in humans, and a recent approval of anthrax vaccine in accordance with the "Animal Rule." The establishment of animal models predictive of vaccine effectiveness in humans has been fraught with difficulties with low success rate to date. Challenges facing the use of animal models for vaccine development against Ebola and HIV will be discussed.}, } @article {pmid28348034, year = {2018}, author = {Martins, MA and Watkins, DI}, title = {What Is the Predictive Value of Animal Models for Vaccine Efficacy in Humans? Rigorous Simian Immunodeficiency Virus Vaccine Trials Can Be Instructive.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {4}, pages = {}, doi = {10.1101/cshperspect.a029504}, pmid = {28348034}, issn = {1943-0264}, abstract = {Simian immunodeficiency virus (SIV) challenge of rhesus macaques provides an invaluable tool to evaluate the clinical prospects of HIV-1 vaccine concepts. However, as with any animal model of human disease, it is crucial to understand the advantages and limitations of this system to maximize the translational value of SIV vaccine studies. Here, we discuss the importance of assessing the efficacy of vaccine prototypes using stringent SIV challenge regimens that mimic HIV-1 transmission and pathogenesis. We also review some of the cautionary tales of HIV-1 vaccine research because they provide general lessons for the preclinical assessment of vaccine candidates.}, } @article {pmid29904510, year = {2018}, author = {Begley, GS}, title = {Using Elevator Speeches to Develop Research & Communication Skills in Biology.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904510}, issn = {1935-7877}, } @article {pmid28330740, year = {2018}, author = {Dagosto, M and Gebo, D and Ni, X and Smith, T}, title = {Estimating body size in early primates: The case of Archicebus and Teilhardina.}, journal = {Journal of human evolution}, volume = {115}, number = {}, pages = {8-19}, doi = {10.1016/j.jhevol.2017.02.005}, pmid = {28330740}, issn = {1095-8606}, abstract = {Obtaining accurate estimations of the body mass of fossil primates has always been a subject of interest in paleoanthropology because mass is an important determinant for so many other aspects of biology, ecology, and life history. This paper focuses on the issues involved in attempting to reconstruct the mass of two early Eocene haplorhine primates, Teilhardina and Archicebus, which pose particular problems due to their small size and temporal and phylogenetic distance from extant primates. In addition to a ranking of variables from more to less useful, the effect of using models of varying taxonomic and size compositions is examined. Phylogenetic correction is also applied to the primate database. Our results indicate that the choice of variable is more critical than the choice of model. The more reliable variables are the mediolateral breadth across the femoral condyles and the area of the calcaneocuboid facet of the calcaneus. These variables suggest a body mass of 39 g (range 33-46 g) for Archicebus and 48 g (range 44-56 g) for Teilhardina. The width of the distal femur is found to be the most consistent estimator across models of various composition and techniques. The effect of phylogenetic correction is small but the choice of branch length assumption affects point estimates for the fossils. The majority of variables and models predict the body mass of Archicebus and Teilhardina to be in the range of the smaller extant mouse lemurs, as expected.}, } @article {pmid28320756, year = {2018}, author = {Pape, KA and Jenkins, MK}, title = {Do Memory B Cells Form Secondary Germinal Centers? It Depends.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, doi = {10.1101/cshperspect.a029116}, pmid = {28320756}, issn = {1943-0264}, abstract = {The memory B-cell pool in an immune individual is more heterogeneous than previously recognized. The different types of memory B cells likely play distinct roles in tuning the secondary immune response because they differ in their potential to generate plasmablasts, which secrete antibodies, or germinal center (GC) cells, which generate new and higher affinity memory cells. We propose that the production of plasmablasts or GC cells by a memory B cell is controlled by its state of differentiation and the amount and affinity of antigen-specific antibodies present in the individual in which it resides.}, } @article {pmid28320754, year = {2018}, author = {Shlomchik, MJ}, title = {Do Memory B Cells Form Secondary Germinal Centers? Yes and No.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, doi = {10.1101/cshperspect.a029405}, pmid = {28320754}, issn = {1943-0264}, support = {R01 AI043603/AI/NIAID NIH HHS/United States ; R01 AI105018/AI/NIAID NIH HHS/United States ; }, abstract = {Memory is the defining feature of the adaptive immune system. Humoral immune memory is largely though not exclusively generated in the germinal center (GC), which spawns long-lived plasma cells that support ongoing serum antibody titers as well as "memory B cells" (MBCs) that persist in the immune host at expanded frequencies. Upon reencounter with antigen, these MBCs are reactivated and potentially can contribute to protection by further expansion, rapid differentiation to antibody-forming cells, and/or reseeding of a new round of GCs along with somatic V region mutation and selection. Here I will discuss what controls these various potential fates of MBCs and the functional significance of different types of MBC reactivation.}, } @article {pmid28320753, year = {2018}, author = {McHeyzer-Williams, LJ and Dufaud, C and McHeyzer-Williams, MG}, title = {Do Memory B Cells Form Secondary Germinal Centers? Impact of Antibody Class and Quality of Memory T-Cell Help at Recall.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, doi = {10.1101/cshperspect.a028878}, pmid = {28320753}, issn = {1943-0264}, support = {R01 AI047231/AI/NIAID NIH HHS/United States ; }, abstract = {Antigen recall can clearly induce a germinal center (GC) reaction. What has become an issue for debate are the origins of the antigen-specific B cells that form memory-response GCs (mGCs). Using antigen labeling and adoptive transfer, memory B cells expressing different antibody class can give rise to mGCs with differing efficiency. Here, we will argue that the range of class-specific memory responses reported across multiple systems represents the spectrum of memory B-cell fate and function. While the formulation of recall immunogen and location of mGCs have an important role, we propose that effective cognate regulation is the key variable influencing recall outcome. These issues remain central to contemporary efforts of rational vaccine design.}, } @article {pmid28289061, year = {2018}, author = {Kahata, K and Maturi, V and Moustakas, A}, title = {TGF-β Family Signaling in Ductal Differentiation and Branching Morphogenesis.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a031997}, pmid = {28289061}, issn = {1943-0264}, abstract = {Epithelial cells contribute to the development of various vital organs by generating tubular and/or glandular architectures. The fully developed forms of ductal organs depend on processes of branching morphogenesis, whereby frequency, total number, and complexity of the branching tissue define the final architecture in the organ. Some ductal tissues, like the mammary gland during pregnancy and lactation, disintegrate and regenerate through periodic cycles. Differentiation of branched epithelia is driven by antagonistic actions of parallel growth factor systems that mediate epithelial-mesenchymal communication. Transforming growth factor-β (TGF-β) family members and their extracellular antagonists are prominently involved in both normal and disease-associated (e.g., malignant or fibrotic) ductal tissue patterning. Here, we discuss collective knowledge that permeates the roles of TGF-β family members in the control of the ductal tissues in the vertebrate body.}, } @article {pmid28289060, year = {2018}, author = {Margolis, B}, title = {The Crumbs3 Polarity Protein.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, doi = {10.1101/cshperspect.a027961}, pmid = {28289060}, issn = {1943-0264}, abstract = {The Crumbs proteins are evolutionarily conserved apical transmembrane proteins. Drosophila Crumbs was discovered via its crucial role in epithelial polarity during fly embryogenesis. Crumbs proteins have variable extracellular domains but a highly conserved intracellular domain that can bind FERM and PDZ domain proteins. Mammals have three Crumbs genes and this review focuses on Crumbs3, the major Crumbs isoform expressed in mammalian epithelial cells. Although initial work has highlighted the role of Crumbs3 in polarity, more recent studies have found it has an important role in tissue morphogenesis functioning as a linker between the apical membrane and the actin cytoskeleton. In addition, recent publications have linked Crumbs3 to growth control via regulation of the Hippo/Yap pathway.}, } @article {pmid28264821, year = {2018}, author = {Apodaca, G}, title = {Role of Polarity Proteins in the Generation and Organization of Apical Surface Protrusions.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, pmid = {28264821}, issn = {1943-0264}, support = {P30 DK079307/DK/NIDDK NIH HHS/United States ; R01 DK099196/DK/NIDDK NIH HHS/United States ; R01 DK104287/DK/NIDDK NIH HHS/United States ; }, abstract = {Protruding from the apical surfaces of epithelial cells are specialized structures, including cilia, microplicae, microvilli, and stereocilia. These contribute to epithelial function by cushioning the apical surface, by amplifying its surface area to facilitate nutrient absorption, and by promoting sensory transduction and barrier function. Despite these important roles, and the diseases that result when their formation is perturbed, there remain significant gaps in our understanding of the biogenesis of apical protrusions, or the pathways that promote their organization and orientation once at the apical surface. Here, I review some general aspects of these apical structures, and then discuss our current understanding of their formation and organization with respect to proteins that specify apicobasolateral polarity and planar cell polarity.}, } @article {pmid28264820, year = {2018}, author = {Kreitzer, G and Myat, MM}, title = {Microtubule Motors in Establishment of Epithelial Cell Polarity.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a027896}, pmid = {28264820}, issn = {1943-0264}, abstract = {Epithelial cells play a key role in insuring physiological homeostasis by acting as a barrier between the outside environment and internal organs. They are also responsible for the vectorial transport of ions and fluid essential to the function of many organs. To accomplish these tasks, epithelial cells must generate an asymmetrically organized plasma membrane comprised of structurally and functionally distinct apical and basolateral membranes. Adherent and occluding junctions, respectively, anchor cells within a layer and prevent lateral diffusion of proteins in the outer leaflet of the plasma membrane and restrict passage of proteins and solutes through intercellular spaces. At a fundamental level, the establishment and maintenance of epithelial polarity requires that signals initiated at cell-substratum and cell-cell adhesions are transmitted appropriately and dynamically to the cytoskeleton, to the membrane-trafficking machinery, and to the regulation of occluding and adherent junctions. Rigorous descriptive and mechanistic studies published over the last 50 years have provided great detail to our understanding of epithelial polarization. Yet still, critical early steps in morphogenesis are not yet fully appreciated. In this review, we discuss how cytoskeletal motor proteins, primarily kinesins, contribute to coordinated modification of microtubule and actin arrays, formation and remodeling of cell adhesions to targeted membrane trafficking, and to initiating the formation and expansion of an apical lumen.}, } @article {pmid28264819, year = {2018}, author = {Hammond, GR and Hong, Y}, title = {Phosphoinositides and Membrane Targeting in Cell Polarity.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {2}, pages = {}, doi = {10.1101/cshperspect.a027938}, pmid = {28264819}, issn = {1943-0264}, abstract = {Selective enrichment of the polyphosphoinositides (PPIn), such as PtdIns(4,5)P2 and PtdIns4P, helps to determine the identity of the plasma membrane (PM) and regulates many aspects of cell biology through a vast number of protein effectors. Polarity proteins had long been assumed to be non-PPIn-binding proteins that mainly associate with PM/cell cortex through their extensive protein-protein interaction network. However, recent studies began to reveal that several key polarity proteins electrostatically bind to PPIn through their positively charged protein domains or structures and such PPIn-binding property is essential for their direct and specific attachment to PM. Although the physical nature of the charge-based PPIn binding appears to be simple and nonspecific, it serves as an elegant mechanism that can be efficiently and specifically regulated for achieving polarized PM targeting of polarity proteins. As an unexpected consequence, subcellular localization of PPIn-binding polarity proteins are also subject to regulations by physiological conditions such as hypoxia and ischemia that acutely and reversibly depletes PPIn from PM.}, } @article {pmid28264818, year = {2018}, author = {Engevik, AC and Goldenring, JR}, title = {Trafficking Ion Transporters to the Apical Membrane of Polarized Intestinal Enterocytes.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, pmid = {28264818}, issn = {1943-0264}, support = {F32 DK111101/DK/NIDDK NIH HHS/United States ; R01 DK048370/DK/NIDDK NIH HHS/United States ; R01 DK070856/DK/NIDDK NIH HHS/United States ; T32 CA106183/CA/NCI NIH HHS/United States ; }, abstract = {Epithelial cells lining the gastrointestinal tract require distinct apical and basolateral domains to function properly. Trafficking and insertion of enzymes and transporters into the apical brush border of intestinal epithelial cells is essential for effective digestion and absorption of nutrients. Specific critical ion transporters are delivered to the apical brush border to facilitate fluid and electrolyte uptake. Maintenance of these apical transporters requires both targeted delivery and regulated membrane recycling. Examination of altered apical trafficking in patients with Microvillus Inclusion disease caused by inactivating mutations in MYO5B has led to insights into the regulation of apical trafficking by elements of the apical recycling system. Modeling of MYO5B loss in cell culture and animal models has led to recognition of Rab11a and Rab8a as critical regulators of apical brush border function. All of these studies show the importance of apical membrane trafficking dynamics in maintenance of polarized epithelial cell function.}, } @article {pmid28264817, year = {2018}, author = {Polgar, N and Fogelgren, B}, title = {Regulation of Cell Polarity by Exocyst-Mediated Trafficking.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {3}, pages = {}, pmid = {28264817}, issn = {1943-0264}, support = {K01 DK087852/DK/NIDDK NIH HHS/United States ; P20 GM103457/GM/NIGMS NIH HHS/United States ; P30 DK074038/DK/NIDDK NIH HHS/United States ; R03 DK100738/DK/NIDDK NIH HHS/United States ; }, abstract = {One requirement for establishing polarity within a cell is the asymmetric trafficking of intracellular vesicles to the plasma membrane. This tightly regulated process creates spatial and temporal differences in both plasma membrane composition and the membrane-associated proteome. Asymmetric membrane trafficking is also a critical mechanism to regulate cell differentiation, signaling, and physiology. Many eukaryotic cell types use the eight-protein exocyst complex to orchestrate polarized vesicle trafficking to certain membrane locales. Members of the exocyst were originally discovered in yeast while screening for proteins required for the delivery of secretory vesicles to the budding daughter cell. The same eight exocyst genes are conserved in mammals, in which the specifics of exocyst-mediated trafficking are highly cell-type-dependent. Some exocyst members bind to certain Rab GTPases on intracellular vesicles, whereas others localize to the plasma membrane at the site of exocytosis. Assembly of the exocyst holocomplex is responsible for tethering these vesicles to the plasma membrane before their soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE)-mediated exocytosis. In this review, we will focus on the role and regulation of the exocyst complex in targeted vesicular trafficking as related to the establishment and maintenance of cellular polarity. We will contrast exocyst function in apicobasal epithelial polarity versus front-back mesenchymal polarity, and the dynamic regulation of exocyst-mediated trafficking during cell phenotype transitions.}, } @article {pmid28246184, year = {2018}, author = {Kahata, K and Dadras, MS and Moustakas, A}, title = {TGF-β Family Signaling in Epithelial Differentiation and Epithelial-Mesenchymal Transition.}, journal = {Cold Spring Harbor perspectives in biology}, volume = {10}, number = {1}, pages = {}, doi = {10.1101/cshperspect.a022194}, pmid = {28246184}, issn = {1943-0264}, abstract = {Epithelia exist in the animal body since the onset of embryonic development; they generate tissue barriers and specify organs and glands. Through epithelial-mesenchymal transitions (EMTs), epithelia generate mesenchymal cells that form new tissues and promote healing or disease manifestation when epithelial homeostasis is challenged physiologically or pathologically. Transforming growth factor-βs (TGF-βs), activins, bone morphogenetic proteins (BMPs), and growth and differentiation factors (GDFs) have been implicated in the regulation of epithelial differentiation. These TGF-β family ligands are expressed and secreted at sites where the epithelium interacts with the mesenchyme and provide paracrine queues from the mesenchyme to the neighboring epithelium, helping the specification of differentiated epithelial cell types within an organ. TGF-β ligands signal via Smads and cooperating kinase pathways and control the expression or activities of key transcription factors that promote either epithelial differentiation or mesenchymal transitions. In this review, we discuss evidence that illustrates how TGF-β family ligands contribute to epithelial differentiation and induce mesenchymal transitions, by focusing on the embryonic ectoderm and tissues that form the external mammalian body lining.}, } @article {pmid29904527, year = {2018}, author = {Bhatt, JM and Challa, AK}, title = {First Year Course-Based Undergraduate Research Experience (CURE) Using the CRISPR/Cas9 Genome Engineering Technology in Zebrafish.}, journal = {Journal of microbiology & biology education}, volume = {19}, number = {1}, pages = {}, pmid = {29904527}, issn = {1935-7877}, abstract = {Genetic analysis in model systems can provide a rich context for conceptual understanding of gene structure, regulation, and function. With an intent to create a rich learning experience in molecular genetics, we developed a semester-long course-based undergraduate research experience (CURE) using the CRISPR-Cas9 gene editing system to disrupt specific genes in the zebrafish. The course was offered to freshman students; nine students worked in four groups (two to three members per group) to design, synthesize, and test the nuclease activity of the CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/sgRNAs for targeted disruption of specific genes in the zebrafish. Each group worked with a gene with an already known mutant phenotype that can be visually scored and a gene that had not been studied in zebrafish previously. Embedded in the course were a series of workshop-styled units or tutorials, including tours to core facilities. The focus was on introducing and developing skills that could be accommodated within the span of a semester. Each group successfully cloned at least one plasmid-encoding CRISPR/sgRNA template, visually analyzed injected embryos, and performed genotyping assays to detect CRISPR-Cas9 activity. In-class discussions, a final end-of-semester written test, and group oral presentations were assessed for an understanding of the CRISPR-Cas9 system, application of the CRISPR-Cas9 system as a gene manipulation tool, and experimental methods used to create plasmid vectors and synthesize sgRNA. In addition, poster presentations were evaluated by faculty, graduate students, and senior undergraduate students at a University research exposition. Self-reflections in the form of group conversations were video recorded. All students (9/9) distinctly showed learning gains after completing the activity, but the extent of the gains was variable, as seen from results of a written test and poster presentation assessment. Qualitative analysis of evaluations and self-reporting data indicated several gains, suggesting that all students found many aspects of the CURE valuable and gained project-specific (conceptual) and transferrable skills (science process and science identity).}, } @article {pmid28089508, year = {2018}, author = {Sahle, Y and Braun, DR}, title = {A reply to Douze and Delagnes's 'The pattern of emergence of a Middle Stone Age tradition at Gademotta and Kulkuletti (Ethiopia) through convergent tool and point technologies' [J. Hum. Evol. 91 (2016) 93-121].}, journal = {Journal of human evolution}, volume = {125}, number = {}, pages = {201-206}, doi = {10.1016/j.jhevol.2016.10.005}, pmid = {28089508}, issn = {1095-8606}, abstract = {Douze and Delagnes (2016) revisit Middle Stone Age (MSA) lithic assemblages from the Gademotta Formation (Fm.), Ethiopia. Their analysis of selected assemblages from three of the 1972 excavations expands the original typo-technological interpretations by Wendorf and Schild (1974). We particularly welcome their evaluation of our recent inferences about the function of pointed artifacts and technological patterns in the Gademotta Fm. (Sahle et al., 2013, 2014). However, we find several arguments and conclusions in Douze and Delagnes (2016) to be rather unconvincing and irreconcilable with results from analyses of whole assemblages (Wendorf and Schild, 1974; Sahle et al., 2013, 2014). Specifically, their summary attribution of all early MSA burin-like fractures on the distal tips of pointed artifacts to intentional resharpening blows, and their use of this pattern as a technological "chrono-marker" unique to the region are untenable. Here, we highlight these issues in the hopes of a clearer understanding of the evident technological patterns in the Gademotta Fm.}, }